PMID- 22846869
TI  - Locally advanced pancreatic cancer.

PMID- 22846870
TI  - Palladium-catalyzed direct arylation of benzoxazoles with unactivated simple
      arenes.
AB  - Using CuBr(2) as an additive, the Pd-catalyzed intermolecular C-H-C-H cross
      coupling between benzoxazoles and unactivated simple arenes has been developed.
      This protocol provides a straightforward approach for the biological activity of
      2-arylbenzoxazole derivatives.

PMID- 22846872
TI  - A sandwich assay for quantitative detection of transcription factors in cell
      lysate.
AB  - A double-stranded DNA (dsDNA) mediated sandwich assay was developed for
      quantitative detection of transcription factors. The detection limit for human
      recombinant c-jun protein is 2.5 ng, and for c-jun protein the limit is as low as
      0.625 MUg of cell lysate.

PMID- 22846873
TI  - Screening heavy metals levels in hair of sanitation workers by X-ray fluorescence
      analysis.
AB  - This work presents a study of human hair as a bio-indicator for detection of
      heavy metals as part of environmental health surveillance programs project to
      develop a subject of interest in the biomedical and environmental sciences. A
      total of 34 hair samples were analyzed that consisting of 29 samples from
      sanitation workers and five samples from students. The hair samples were prepared
      and treated in accordance to the International Atomic Energy Agency (IAEA)
      recommendations. The concentrations of heavy metals were analyzed using the
      energy dispersive X-ray fluorescence (EDXRF) technique by X-50 Mobile X-ray
      Fluorescence (XRF) at Oceanography Institute, Universiti Malaysia Terengganu. The
      performance of EDXRF analyzer was tested by Standard Reference Material (SRM
      2711) Montana Soil which was in good agreement with certified value within 14%
      deviations except for Hg. While seven heavy metals: Mn, Fe, Ni, Cu, Zn, Se, and
      Sb were detected in both groups, three additional elements, i.e. As, Hg and Pb,
      were detected only in sanitation workers group. For sanitation workers group, the
      mean concentration of six elements, Mn, Fe, Cu, Zn, Se, and Sb, shows elevated
      concentration as compared to the control samples concentration. Results from both
      groups were compared and discussed in relation to their respective heavy metals
      concentrations.

PMID- 22846874
TI  - Artificial neural network application for predicting soil distribution
      coefficient of nickel.
AB  - The distribution (or partition) coefficient (K(d)) is an applicable parameter for
      modeling contaminant and radionuclide transport as well as risk analysis.
      Selection of this parameter may cause significant error in predicting the impacts
      of contaminant migration or site-remediation options. In this regards, various
      models were presented to predict K(d) values for different contaminants specially
      heavy metals and radionuclides. In this study, artificial neural network (ANN) is
      used to present simplified model for predicting K(d) of nickel. The main
      objective is to develop a more accurate model with a minimal number of
      parameters, which can be determined experimentally or select by review of
      different studies. In addition, the effects of training as well as the type of
      the network are considered. The K(d) values of Ni is strongly dependent on pH of
      the soil and mathematical relationships were presented between pH and K(d) of
      nickel recently. In this study, the same database of these presented models was
      used to verify that neural network may be more useful tools for predicting of
      K(d). Two different types of ANN, multilayer perceptron and redial basis
      function, were used to investigate the effect of the network geometry on the
      results. In addition, each network was trained by 80 and 90% of the data and
      tested for 20 and 10% of the rest data. Then the results of the networks compared
      with the results of the mathematical models. Although the networks trained by 80
      and 90% of the data the results show that all the networks predict with higher
      accuracy relative to mathematical models which were derived by 100% of data. More
      training of a network increases the accuracy of the network. Multilayer
      perceptron network used in this study predicts better than redial basis function
      network.

PMID- 22846875
TI  - Orexin A expression and promoter methylation in patients with cannabis dependence
      in comparison to nicotine-dependent cigarette smokers and nonsmokers.
AB  - BACKGROUND: The orexins (hypocretins) are neuropeptides with an origin in the
      lateral hypothalamus. They have been found to be crucial within the context of
      drug craving, withdrawal und relapse. METHODS: Therefore, orexin A gene
      expression and promoter methylation in peripheral blood cells of 77 subjects [36
      with tetrahydrocannabinol (THC) dependence, 20 nicotine-dependent cigarette
      smokers and 21 nonsmokers] were assessed by quantitative real-time PCR and
      methylation-specific digestion PCR. RESULTS: There was a statistically
      significant difference in orexin A expression between the three groups [p =
      0.000, F = 131.4, d.f. = 2, analysis of variance (ANOVA)]. Orexin A gene
      expression was statistically significantly correlated with the Satisfaction with
      Life Scale (r = -0.28, p = 0.018), a visual analogue scale of craving (r = 0.734,
      p = 0.000) and three subscales of the World Health Organization Alcohol, Smoking
      and Substance Involvement Screening Test, i.e. nicotine consumption (r = 0.388, p
      = 0.001), alcohol consumption (r = 0.354, p = 0.002) and cannabis consumption (r
      = 0.783, p = 0.000). The mean promoter methylation (as a percentage) was not
      statistically related to orexin gene expression. However, there was a
      statistically significant difference in promoter methylation with regard to body
      mass index in general (F = 2.37, d.f. = 54, p = 0.016, ANOVA). CONCLUSIONS:
      Orexin might be a possible target in THC as well as nicotine dependence, taking
      into account the effect of THC on energy homeostasis in the circuit of reward and
      motivation and its impact on appetite and body weight.

PMID- 22846876
TI  - Time-loss injuries versus non-time-loss injuries in the first team rugby league
      football:  a pooled data analysis.
AB  - OBJECTIVE: To describe the injury rates in first team rugby league in terms of
      those injuries that require missed playing time and those that do not. DESIGN: A
      pooled data analysis from 2 independent databases. SETTING: Rugby league match
      and training environment over several seasons from 1990 to 2003. MAIN OUTCOME
      MEASURES: Injuries were reported as rates per 1000 hours of participation and as
      percentages with their associated 95% confidence intervals (CIs). RESULTS: A
      total of 1707 match injuries were recorded. Of these injuries, 257 required
      players to miss the subsequent match. The remaining 1450 injuries did not require
      players to miss the next game. They represented 85% (95% CI, 83-87) of all
      injuries received and recorded. The ratio of non-time-loss (NTL) to time-loss
      (TL) injuries was 5.64 (95% CI, 4.96-6.42). There were 450 training injuries, of
      which 81 were TL injuries and 369 NTL injuries. The NTL training injury rate was
      4.56 (95% CI, 3.58-5.79) times higher than TL injury rate. CONCLUSIONS: Non-time
      loss injuries represent the largest proportion of injuries in rugby league. If
      NTL injuries are not recorded, the workload of practitioners is likely to be
      severely underestimated.

PMID- 22846877
TI  - An evidence-based systematic review on cognitive interventions for individuals
      with dementia.
AB  - PURPOSE: To evaluate the current state of research evidence related to cognitive
      interventions for individuals with Alzheimer's disease or related dementias.
      METHOD: A systematic search of the literature was conducted across 27 electronic
      databases based on a set of a priori questions, inclusion/exclusion criteria, and
      search parameters. Studies were appraised for methodological quality and
      categorized according to intervention technique and outcome (e.g., cognitive
      communication impairment or activity limitation/participation restriction).
      Results were summarized and, when possible, analyzed quantitatively using
      indicators of treatment effect size. RESULTS: Forty-three studies met criteria
      for inclusion in the review. The most commonly used cognitive intervention
      techniques used were errorless learning, spaced-retrieval training, vanishing
      cues, or verbal instruction/cueing. Most treatment outcomes were measured at the
      cognitive-communication impairment level of functioning and were generally
      positive. However, results should be interpreted cautiously because of
      methodological limitations across studies. CONCLUSIONS: Research evidence to
      support the use of cognitive interventions for individuals with dementia is
      accumulating. Researchers are beginning to evaluate treatment efficacy, yet the
      focus tends to be on discovery, specifically, refining intervention variables
      that will facilitate optimal outcomes. Implications for clinical practice and
      avenues for future research are discussed.

PMID- 22846878
TI  - Communicative gesture use in infants with and without autism: a retrospective
      home video study.
AB  - PURPOSE: The authors aimed to compare gesture use in infants with autism with
      gesture use in infants with other developmental disabilities (DD) or typical
      development (TD). METHOD: Children with autism (n = 43), DD (n = 30), and TD (n =
      36) were recruited at ages 2 to 7 years. Parents provided home videotapes of
      children in infancy. Staff compiled video samples for 2 age intervals (9-12 and
      15-18 months) and coded samples for frequency of social interaction (SI),
      behavior regulation (BR), and joint attention (JA) gestures. RESULTS: At 9-12
      months, infants with autism were less likely to use JA gestures than infants with
      DD or TD, and less likely to use BR gestures than infants with TD. At 15-18
      months, infants with autism were less likely than infants with DD to use SI or JA
      gestures, and less likely than infants with TD to use BR, SI, or JA gestures.
      Among infants able to use gestures, infants with autism used fewer BR gestures
      than those with TD at 9-12 months, and fewer JA gestures than infants with DD or
      TD at 15-18 months. CONCLUSION: Differences in gesture use in infancy have
      implications for early autism screening, assessment, and intervention.

PMID- 22846879
TI  - Procedural visual learning in children with specific language impairment.
AB  - PURPOSE: According to the procedural deficit hypothesis (PDH), difficulties in
      the procedural learning (PL) system may contribute to the language difficulties
      observed in children with specific language impairment (SLI). METHOD: Fifteen
      children with SLI and their typically developing (TD) peers were compared on
      visual PL tasks-specifically, deterministic serial reaction time (SRT) tasks. In
      the first experiment, children with SLI and their TD peers performed the
      classical SRT task using a keyboard as response mode. In the second experiment,
      they performed the same SRT task but gave their responses through a touchscreen
      (instead of a keyboard) to reduce the motor and cognitive demands of the task.
      RESULTS: Although in Experiment 1, children with SLI demonstrated learning, they
      were slower and made more errors than did their TD peers. Nevertheless, these
      relative weaknesses disappeared when the nature of the response mode changed (
      Experiment 2). CONCLUSIONS: In this study, the authors report that children with
      SLI may exhibit sequential learning. Moreover, the generally slower reaction
      times observed in previous deterministic SRT studies may be explained by the
      response mode used. Thus, our findings are not consistent with the predictions of
      the PDH, and these findings suggest that language impairments in SLI are not
      sustained by poor procedural learning abilities.

PMID- 22846881
TI  - "The caterpillar": a novel reading passage for assessment of motor speech
      disorders.
AB  - PURPOSE: A review of the salient characteristics of motor speech disorders and
      common assessment protocols revealed the need for a novel reading passage
      tailored specifically to differentiate between and among the dysarthrias (DYSs)
      and apraxia of speech (AOS). METHOD: "The Caterpillar" passage was designed to
      provide a contemporary, easily read, contextual speech sample with specific tasks
      (e.g., prosodic contrasts, words of increasing length and complexity) targeted to
      inform the assessment of motor speech disorders. Twenty-two adults, 15 with DYS
      or AOS and 7 healthy controls (HC), were recorded reading "The Caterpillar"
      passage to demonstrate its utility in examining motor speech performance.
      CONCLUSION: Analysis of performance across a subset of segmental and prosodic
      variables illustrated that "The Caterpillar" passage showed promise for
      extracting individual profiles of impairment that could augment current
      assessment protocols and inform treatment planning in motor speech disorders.

PMID- 22846880
TI  - Impact of typical aging and Parkinson's disease on the relationship among breath
      pausing, syntax, and punctuation.
AB  - PURPOSE: The present study examines the impact of typical aging and Parkinson's
      disease (PD) on the relationship among breath pausing, syntax, and punctuation.
      METHOD: Thirty young adults, 25 typically aging older adults, and 15 individuals
      with PD participated. Fifteen participants were age- and sex-matched to the
      individuals with PD. Participants read a passage aloud 2 times. Utterance length,
      location of breath pauses relative to punctuation and syntax, and number of
      disfluencies and mazes were measured. RESULTS: Older adults produced shorter
      utterances, a smaller percentage of breaths at major boundaries, and a greater
      percentage of breaths at minor boundaries than did young adults, but there was no
      significant difference between older adults and individuals with PD on these
      measures. Individuals with PD took a greater percentage of breaths at locations
      unrelated to a syntactic boundary than did control participants. Individuals with
      PD produced more mazes than did control participants. Breaths were significantly
      correlated with punctuation for all groups. CONCLUSIONS: Changes in breath
      pausing patterns in older adults are likely due to changes in respiratory
      physiology. However, in individuals with PD, such changes appear to result from a
      combination of changes to respiratory physiology and cognition.

PMID- 22846882
TI  - Consonant production accuracy in young cochlear implant recipients: developmental
      sound classes and word position effects.
AB  - PURPOSE: To compare young cochlear implant (CI) recipients' consonant production
      accuracy with that of age- and gender-matched peers who were typically developing
      (TD). In addition to examining initial consonants, the authors compiled new data
      regarding the accuracy of final consonants and the order of consonant
      acquisition. METHODS: Eleven young CI recipients with 24 months of CI experience
      and 11 age- and gender-matched TD peers produced target words in short sentences.
      Consonant production accuracy was examined for total scores, initial and final
      word positions, and three developmental sound classes: Early, Middle, and Late.
      RESULTS: Initial consonants were produced with relatively greater accuracy than
      were final consonants by the TD and CI groups. Whereas initial consonants
      appeared to be acquired in a typical order, descriptive data suggest that this
      might not be the case for final consonants. CONCLUSIONS: Although still delayed
      compared to age-matched peers, young CI recipients showed substantial progress in
      consonant acquisition. Their accuracy levels after 2 years of CI experience
      support the notion that implantation at a young age has added value for
      phonological development.

PMID- 22846883
TI  - Features of endogenous cardiomyocyte chromatin revealed by super-resolution STED
      microscopy.
AB  - Despite the extensive knowledge of the functional unit of chromatin-the
      nucleosome-for which structural information exists at the atomic level, little is
      known about the endogenous structure of eukaryotic genomes. Chromosomal capture
      techniques and genome-wide chromatin immunoprecipitation and next generation
      sequencing have provided complementary insight into global features of chromatin
      structure, but these methods do not directly measure structural features of the
      genome in situ. This lack of insight is particularly troublesome in terminally
      differentiated cells which must reorganize their genomes for large scale gene
      expression changes in the absence of cell division. For example, cardiomyocytes,
      which are fully committed and reside in interphase, are capable of massive gene
      expression changes in response to physiological stimuli, but the global changes
      in chromatin structure that enable such transcriptional changes are unknown. The
      present study addressed this problem utilizing super-resolution stimulated
      emission depletion (STED) microscopy to directly measure chromatin features in
      mammalian cells. We demonstrate that immunolabeling of histone H3 coupled with
      STED imaging reveals chromatin domains on a scale of 40-70 nm, several folds
      better than the resolution of conventional confocal microscopy. An analytical
      workflow is established to detect changes in chromatin structure following acute
      stimuli and used to investigate rearrangements in cardiomyocyte genomes following
      agonists that induce cellular hypertrophy. This approach is readily adaptable to
      investigation of other nuclear features using a similar antibody-based labeling
      technique and enables direct measurements of chromatin domain changes in response
      to physiological stimuli.

PMID- 22846884
TI  - Pyrolysis characteristics of bean dregs and in situ visualization of pyrolysis
      transformation.
AB  - Biomass is an important renewable and sustainable source of energy. Waste
      products from biomass are considered as attractive feedstocks for the production
      of fuel. This work deals with the pyrolysis of bean dregs, a biomass waste from
      soybean processing industry. A technique has been developed to study bean dregs
      pyrolysis by in situ visualization of bean dregs transformation in a quartz
      capillary under a microscope using a charge-coupled device (CCD) camera
      monitoring system. The technique enables us to observe directly the processes and
      temperatures of bean dregs transformation during pyrolysis. In situ visualization
      of reaction revealed that how oily liquids are generated and expulsed
      concurrently from bean dregs during pyrolysis. Pyrolysis characteristics were
      investigated under a highly purified N(2) atmosphere using a thermogravimetric
      analyzer from room temperature to 800  degrees C at different heating rates of
      10, 30 and 50  degrees C/min. The results showed that three stages appeared in
      this thermal degradation process. The initial decomposition temperature and the
      peak shifted towards higher temperature with an increase in heating rate. Kinetic
      parameters in terms of apparent activation energy and pre-exponential factor were
      determined.

PMID- 22846885
TI  - Involvement of brain ANG II in acute sodium depletion induced salty taste
      changes.
AB  - Many investigations have been devoted to determining the role of angiotensin II
      (ANG II) and aldosterone (ALD) in sodium-depletion-induced sodium appetite, but
      few were focused on the mechanisms mediating the salty taste changes accompanied
      with sodium depletion. To further elucidate the mechanism of renin-angiotensin
      aldosterone system (RAAS) action in mediating sodium intake behavior and
      accompanied salty taste changes, the present study examined the salty taste
      function changes accompanied with sodium depletion induced by furosemide (Furo)
      combined with different doses of angiotensin converting enzyme (ACE) inhibitor,
      captopril (Cap). Both the peripheral and central RAAS activity and the nuclei Fos
      immunoreactivity (Fos-ir) expression in the forebrain area were investigated.
      Results showed that sodium depletion induced by Furo+low-Cap increased taste
      preference for hypertonic NaCl solution with amplified brain action of ANG II but
      without peripheral action, while Furosemide combined with a high dose of
      captopril can partially inhibit the formation of brain ANG II, with parallel
      decreased effects on salty taste changes. And the resulting elevating forebrain
      ANG II may activate a variety of brain areas including SFO, PVN, SON and OVLT in
      sodium depleted rats injected with Furo+low-Cap, which underlines salty taste
      function and sodium intake behavioral changes. Neurons in SFO and OVLT may be
      activated mainly by brain ANG II, while PVN and SON activation may not be
      completely ANG II dependent. These findings suggested that forebrain derived ANG
      II may play a critical role in the salty taste function changes accompanied with
      acute sodium depletion.

PMID- 22846886
TI  - Re: Kontopoulos EV, Gualtieri M, Quintero RA. Successful in utero treatment of an
      oral teratoma via operative fetoscopy: case report and review of literature [Am.
      J. Obstet. Gynecol. 207 (2012) e12-e15].

PMID- 22846887
TI  - Clam farming generates CO2: A study case in the Marinetta lagoon (Italy).
AB  - Respiration and calcium carbonate (CaCO(3)) production by the farmed short-neck
      clam Ruditapes philippinarum were calculated to assess their importance as carbon
      dioxide (CO(2)) sink/source in a lagoon of the Po Delta River (Italy). Biomass
      and calcimass were established by monthly harvests during a 1-year period (2009).
      The ratio of CO(2) released to CaCO(3) precipitated was calculated as a function
      of the near-bottom temperature. From our estimates, R. philippinarum sequestered 
      [Formula: see text]  for shell formation, but the CO(2) fluxes due to respiration
      and calcification resulted 22.7 and 5.56  [Formula: see text] , respectively.
      Clam farming seems therefore to be a significant additional source of CO(2) to
      seawater.

PMID- 22846888
TI  - Human viral diseases: what is next for antiviral drug discovery?
AB  - For the treatment of human immunodeficiency virus (HIV) infections for which
      there are ample drugs available, the immediate future lies in a once-daily
      combination pill containing three or four active ingredients. This strategy may
      also be envisaged for the treatment of hepatitis C virus (HCV) infections as soon
      as we have at hand the appropriate direct-acting antiviral agents (DAAs) to be
      combined. A combination drug therapy is generally not entertained for other
      viruses. Yet, new drugs are at the horizon for the treatment of herpes simplex
      virus (HSV), varicella-zoster virus (VZV), poxvirus, hepatitis B virus (HBV),
      influenza and enveloped viruses-at-large.

PMID- 22846889
TI  - Biodecolorization and biodegradation of reactive Levafix Blue E-RA granulate dye
      by the white rot fungus Irpex lacteus.
AB  - The treatment of effluents from textile industry with microorganisms, especially
      bacteria and fungi, has recently gained attention. The present study was
      conducted using white rot fungi Irpex lacteus, Trametes hirsuta, Trametes sp.,
      and Lentinula edodes for the decolorization of reactive textile Levafix Blue E-RA
      granulate dye. I. lacteus resulted in the best decolorization and degradation of
      the dye within four days. Therefore, more detailed studies were carried out using
      I. lacteus. The decolorization was evaluated at various concentration, pH values,
      and temperatures. The activities of laccase, manganese peroxidase, and lignin
      peroxidase enzymes were estimated to reveal the roles of enzymes in
      decolorization. The colorless nature of the fungal cells revealed that
      decolorization occurred through degradation, and confirmed by analysis of the
      metabolites by UV-visible spectroscopy and High Performance Liquid Chromatography
      after decolorization. The metabolites were identified by Gas Chromatography-Mass
      Spectrometry, and functional group analysis was performed by Fourier Transform
      Infrared Spectroscopy. The degraded dye metabolites were assessed for
      phytotoxicity using Vigna radiata and Brassica juncea, which demonstrated
      nontoxic nature of the metabolites formed after degradation of dye.

PMID- 22846890
TI  - EDS measurements of X-ray intensity at WDS precision and accuracy using a silicon
      drift detector.
AB  - The accuracy and precision of X-ray intensity measurements with a silicon drift
      detector (SDD) are compared with the same measurements performed on a wavelength
      dispersive spectrometer (WDS) for a variety of elements in a variety of
      materials. In cases of major (>0.10 mass fraction) and minor (>0.01 mass
      fraction) elements, the SDD is demonstrated to perform as well or better than the
      WDS. This is demonstrated both for simple cases in which the spectral peaks do
      not interfere (SRM-481, SRM-482, and SRM-479a), and for more difficult cases in
      which the spectral peaks have significant interferences (the Ba L/Ti K lines in a
      series of Ba/Ti glasses and minerals). We demonstrate that even in the case of
      significant interference high count SDD spectra are capable of accurately
      measuring Ti in glasses with Ba:Ti mass fraction ratios from 2.7:1 to 23.8:1. The
      results suggest that for many measurements wavelength spectrometry can be
      replaced with an SDD with improved accuracy and precision.

PMID- 22846892
TI  - Human S100A3 tetramerization propagates Ca(2+)/Zn(2+) binding states.
AB  - The S100A3 homotetramer assembles upon citrullination of a specific symmetric
      Arg51 pair on its homodimer interface in human hair cuticular cells. Each S100A3
      subunit contains two EF-hand-type Ca(2+)-binding motifs and one (Cys)3His-type
      Zn(2+)-binding site in the C-terminus. The C-terminal coiled domain is cross
      linked to the presumed docking surface of the dimeric S100A3 via a disulfide
      bridge. The aim of this study was to determine the structural and functional role
      of the C-terminal Zn(2+)-binding domain, which is unique to S100A3, in
      homotetramer assembly. The binding of either Ca(2+) or Zn(2+) reduced the alpha
      helix content of S100A3 and modulated its affinity for the other cation. The
      binding of a single Zn(2+) accelerated the Ca(2+)-dependent tetramerization of
      S100A3 while inducing an extensive unfolding of helix IV. The Ca(2+) and Zn(2+)
      binding affinities of S100A3 were enhanced when the other cation bound in concert
      with the tetramerization of S100A3. Small angle scattering analyses revealed that
      the overall structure of the S100A3 tetramer bound both Ca(2+) and Zn(2+) had a
      similar molecular shape to the Ca(2+)-bound form in solution. The binding states
      of the Ca(2+) or Zn(2+) to each S100A3 subunit within a homotetramer appear to be
      propagated by sensing the repositioning of helix III and the rearrangement of the
      C-terminal tail domain. This article is part of a Special Issue entitled: 12th
      European Symposium on Calcium.

PMID- 22846893
TI  - Atomic/molecular layer deposited thin-film alloys of Ti-4,4'-oxydianiline hybrid
      TiO2 with tunable properties.
AB  - By combining atomic layer deposition (ALD) and molecular layer deposition (MLD)
      thin-film techniques, the latter being a variant of the former in which organic
      precursors are used, it is possible to deposit thin films containing precisely
      controlled portions of inorganic and organic constituents. This in turn enables
      the adjustment of material properties by changing the number of ALD and MLD
      cycles applied during the deposition. In this work, the properties of such thin
      film "alloys" prepared by varying the portions of Ti-4,4'-oxydianiline (Ti-ODA)
      inorganic-organic hybrid and TiO(2) in the structure were investigated. The films
      were deposited at 280  degrees C using TiCl(4) and water as precursors for
      TiO(2), and TiCl(4) and ODA for the Ti-ODA hybrid. The results demonstrate
      excellent tunability of the film properties such as degree of crystallinity,
      roughness, refractive index, and hardness depending on the relative number of
      TiO(2) and Ti-ODA cycles employed.

PMID- 22846894
TI  - Radioembolization and chemoembolization for unresectable neuroendocrine liver
      metastases - a systematic review.
AB  - This review examines the clinical efficacy and safety of the use of hepatic
      arterial chemoembolization, bland embolization and radioembolization in the
      treatment of unresectable neuroendocrine tumor liver metastases (NETLM). Response
      to treatment, survival outcome and toxicity were examined in this review of 37
      studies comprising 1575 patients. These therapies are safe and effective in the
      treatment of NETLM. Prospective clinical trials to compare the relative efficacy
      and toxicity are warranted.

PMID- 22846895
TI  - Influence of erroneous patient records on population pharmacokinetic modeling and
      individual bayesian estimation.
AB  - BACKGROUND: Observational data sets can be used for population pharmacokinetic
      (PK) modeling. However, these data sets are generally less precisely recorded
      than experimental data sets. This article aims to investigate the influence of
      erroneous records on population PK modeling and individual maximum a posteriori
      Bayesian (MAPB) estimation. METHODS: A total of 1123 patient records of neonates
      who were administered vancomycin were used for population PK modeling by
      iterative 2-stage Bayesian (ITSB) analysis. Cut-off values for weighted residuals
      were tested for exclusion of records from the analysis. A simulation study was
      performed to assess the influence of erroneous records on population modeling and
      individual MAPB estimation. Also the cut-off values for weighted residuals were
      tested in the simulation study. RESULTS: Errors in registration have limited the
      influence on outcomes of population PK modeling but can have detrimental effects
      on individual MAPB estimation. A population PK model created from a data set with
      many registration errors has little influence on subsequent MAPB estimates for
      precisely recorded data. A weighted residual value of 2 for concentration
      measurements has good discriminative power for identification of erroneous
      records. CONCLUSIONS: ITSB analysis and its individual estimates are hardly
      affected by most registration errors. Large registration errors can be detected
      by weighted residuals of concentration.

PMID- 22846896
TI  - Impact of interferences including metabolite crossreactivity on therapeutic drug
      monitoring results.
AB  - Therapeutic drug monitoring is an integral part of services offered by toxicology
      laboratories because certain drugs require routine monitoring for dosage
      adjustment to achieve optimal therapeutic response and avoid adverse drug
      reactions. Immunoassays are widely used for therapeutic drug monitoring. However,
      immunoassays suffer from interferences from both exogenous and endogenous
      compounds including metabolites of the parent drug. Digoxin immunoassays are
      affected more commonly than any other immunoassays used for therapeutic drug
      monitoring. Digoxin immunoassays are affected by endogenous digoxin-like
      immunoreactive substances and exogenous compounds such as various drugs, certain
      herbal supplements, and Digibind. Carbamazepine is metabolized to carbamazepine
      10, 11-epoxide, and the crossreactivity of this metabolite with carbamazepine
      immunoassay may vary from 0% to 94%. Immunoassays used for measuring
      concentrations of tricyclic antidepressants are affected by tricyclic
      antidepressant metabolites and by a number of other drugs. Immunoassays for
      immunosuppressants are also subjected to significant interferences from
      metabolites, and liquid chromatography combined with mass spectrometry or tandem
      mass spectrometry is recommended for therapeutic drug monitoring of
      immunosuppressants. However, liquid chromatography combined with mass
      spectrometry may also suffer from interferences, for example, due to ion
      suppression or from isobaric ions.

PMID- 22846897
TI  - Therapeutic drug monitoring in pregnancy.
AB  - Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing
      regimens of various medications. It has been proposed to guide therapy in
      pregnant women, in whom physiological changes may lead to altered
      pharmacokinetics resulting in difficulty in predicting the appropriate drug
      dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment
      while minimizing toxicity of both the mother and fetus. Monitoring of drug levels
      may also be helpful in assessing adherence to prescribed therapy in selected
      cases. Limitations exist as therapeutic ranges have only been defined for a
      limited number of drugs and are based on data obtained in nonpregnant patients.
      TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral
      drugs, based on pharmacokinetic studies that have shown reduced drug
      concentrations. However, there is only relatively limited (and sometimes
      inconsistent) information regarding the clinical impact of these pharmacokinetic
      changes during pregnancy and the effect of subsequent dose adjustments. Further
      studies are required to determine whether implementation of TDM during pregnancy
      improves outcome and is associated with any benefit beyond that achieved by
      clinical judgment alone. The cost effectiveness of TDM programs during pregnancy
      also remains to be examined.

PMID- 22846898
TI  - Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral
      administration of fenproporex.
AB  - BACKGROUND: Fenproporex hydrochloride (FEN) is an anorectic drug used in the
      treatment of obesity, and its major metabolite is amphetamine (AMP), another
      central nervous system stimulant. The concentration versus time profile of FEN
      and its metabolite AMP has been described in classic biological matrices such as
      plasma and urine; however, there are no reports of such data in oral fluid.
      OBJECTIVE: The aim of this study is to describe the pharmacokinetics of FEN and
      AMP in oral fluid after intake of FEN. METHODS: Twenty-five milligrams of FEN (1
      capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral
      fluid samples were collected with a Quantisal device during 24.00 hours after
      drug ingestion. These samples were submitted to solid-phase microextraction
      before analysis by gas chromatography-mass spectrometry in the selected-ion
      monitoring mode, using deuterium-labeled AMP as internal standard. RESULTS: After
      FEN administration, both analytes could be detected in oral fluid of all
      volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN
      peak concentrations occurred between 1.00 and 1.50 hours after administration and
      were between 70.7 and 227.5 MUg/L. For AMP, peak concentration occurred between
      1.50 and 4.00 hours, reaching 33.0-150.9 MUg/L. CONCLUSION: The authors observed
      that oral administration of FEN resulted in significant amounts of FEN and AMP in
      oral fluid, showing that oral fluid could be a biological matrix suitable for
      pharmacokinetic studies for both analytes. Using a compartmental approach, FEN
      data were best fitted by 1-compartment model with first-order input and output,
      whereas AMP followed a 2-compartment model with first-order input and output.

PMID- 22846899
TI  - E-NTPDase and E-ADA activities are altered in lymphocytes of patients with
      indeterminate form of Chagas' disease.
AB  - Trypanosoma cruzi infection triggers a chronic inflammatory process in human host
      and purinergic system ecto-enzymes play an important role in modulating the
      inflammatory and immune responses. In this study, it was investigated ecto
      nucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5; CD39) and ecto
      adenosine deaminase (E-ADA; EC 3.5.4.4) activities in lymphocytes from patients
      with indeterminate form of Chagas' disease (IFCD). Twenty-five IFCD patients and
      25 healthy subjects (control group) were selected. The peripheral lymphocytes
      were isolated and E-NTPDase and E-ADA activities were determined. Adenine
      nucleotides and adenosine levels were determined in serum by HPLC and the E
      NTPDase1 expression in lymphocytes by Western blot analysis. E-NTPDase (ATP and
      ADP as substrates) and E-ADA (adenosine as substrate) activities were decreased
      in lymphocytes from IFCD patients (P<0.05 and P<0.01, respectively), while the E
      NTPDase1 expression presented no changes in these patients. Serum ATP levels
      showed to be decreased (P<0.05) and both AMP (P<0.01) and adenosine (P<0.001)
      levels were increased in the IFCD group. The enzymatic alterations observed are
      in agreement with the immune response against T. cruzi infection in IFCD
      patients, since the decreased extracellular ATP and the increased adenosine
      levels trigger a Th2 anti-inflammatory response, which it is associated to
      adaptation of host to parasite, preventing clinical progress of disease.

PMID- 22846900
TI  - Microbial population dynamics and proteomics in membrane bioreactors with
      enzymatic quorum quenching.
AB  - Quorum sensing gives rise to biofilm formation on the membrane surface, which in
      turn causes a loss of water permeability in membrane bioreactors (MBRs) for
      wastewater treatment. Enzymatic quorum quenching was reported to successfully
      inhibit the formation of biofilm in MBRs through the decomposition of signal
      molecules, N-acyl homoserine lactones (AHLs). The aim of this study was to
      elucidate the mechanisms of quorum quenching in more detail in terms of microbial
      population dynamics and proteomics. Microbial communities in MBRs with and
      without a quorum quenching enzyme (acylase) were analyzed using pyrosequencing
      and compared with each other. In the quorum quenching MBR, the rate of
      transmembrane pressure (TMP) rise-up was delayed substantially, and the
      proportion of quorum sensing bacteria with AHL-like autoinducers (such as
      Enterobacter, Pseudomonas, and Acinetobacter) also decreased in the entire
      microbial community of mature biofilm in comparison to that in the control MBR.
      These factors were attributed to the lower production of extracellular polymeric
      substances (EPS), which are known to play a key role in the formation of biofilm.
      Proteomic analysis using the Enterobacter cancerogenus strain ATCC 35316
      demonstrates the possible depression of protein expression related to microbial
      attachments to solid surfaces (outer membrane protein, flagellin) and the
      agglomeration of microorganisms (ATP synthase beta subunit) with the enzymatic
      quorum quenching. It has been argued that changes in the microbial population,
      EPS and proteins via enzymatic quorum quenching could inhibit the formation of
      biofilm, resulting in less biofouling in the quorum quenching MBR.

PMID- 22846901
TI  - Production of the 14C-labeled insecticidal protein Cry1Ab for soil metabolic
      studies using a recombinant Escherichia coli in small-scale batch fermentations.
AB  - Insecticidal Cry proteins naturally produced by Bacillus thuringiensis are a
      major recombinant trait expressed by genetically modified crops. They are
      released into the soil during and after cropping. The objective of this study was
      to produce (14)C-labeled Cry1Ab proteins for soil metabolic studies in scope of
      their environmental risk assessment. Cry1Ab was synthesized as a protoxin by
      Escherichia coli HB101 pMP in 200-mL liquid batch culture fermentations and
      purified from inclusion bodies after trypsin digestion. For cultivation, U-(14)C
      glycerol was the main carbon source. Inclusion bodies were smaller and Cry1Ab
      yield was lower when the initial amount of total organic carbon in the
      cultivation broth was below 6.4 mg C L(-1). Concentrations of 12.6 g (14)C
      labeled glycerol L(-1) (1 % v/v) resulted in the production of 17.1 mg (14)C
      Cry1Ab L(-1) cultivation medium. (14)C mass balances showed that approx. 50 % of
      the label was lost by respiration and 20 % remained in the growth media, while
      the residual activity was associated with biomass. Depending on the production
      batch, 0.01 to 0.05 % of the total (14)C originated from Cry1Ab. In the presence
      of 2.04 MBq (14)C-labeled carbon sources, a specific activity of up to 268 Bq mg(
      1) (14)C-Cry1Ab was obtained. A more than threefold higher specific activity was
      achieved with 4.63 MBq and an extended cultivation period of 144 h. This study
      demonstrates that (14)C-labeled Cry1Ab can be obtained from batch fermentations
      with E. coli in the presence of a simple (14)C-labeled carbon source. It also
      provides a general strategy to produce (14)C-labeled proteins useful for soil
      metabolic studies.

PMID- 22846902
TI  - Application of microorganisms towards synthesis of chiral terpenoid derivatives.
AB  - Biotransformations are a standard tool of green chemistry and thus are following
      the rules of sustainable development. In this article, we describe the most
      common types of reactions conducted by microorganisms applied towards synthesis
      of chiral terpenoid derivatives. Potential applications of obtained products in
      various areas of industry and agriculture are shown. We also describe biological
      activity of presented compounds. Stereoselective hydroxylation, epoxidation,
      Baeyer-Villiger oxidation, stereo- and enantioselective reduction of ketones, and
      various kinetic resolutions carried out by bacteria and fungi have been reviewed.
      Mechanistic considerations regarding chemical and enzymatic reactions are
      presented. We also briefly describe modern approaches towards enhancing desired
      enzymatic activity in order to apply modified biocatalysts as an efficient tool
      and green alternative to chemical catalysts used in industry.

PMID- 22846903
TI  - Transcriptomic responses of Synechocystis sp. PCC 6803 encapsulated in silica
      gel.
AB  - Global gene expression of Synechocystis sp. PCC 6803 encapsulated in silica gel
      was examined by microarray analysis. Cultures were encapsulated in gels derived
      from aqueous precursors or from alkoxide precursors and incubated under constant
      light for 24 h prior to RNA extraction. Cultures suspended in liquid media were
      exposed to 500 mM salt stress and incubated under identical conditions for
      comparison purposes. The expression of 414 genes was significantly altered by
      encapsulation in aqueous-derived gels (fold change >=1.5 and P value < 0.01), the
      expression of 1,143 genes was significantly altered by encapsulation in alkoxide
      derived gels, and only 243 genes were common to both encapsulation chemistries.
      Additional qRT-PCR analyses of four selected genes, ggpS, cpcG2, slr5055, and
      sll5057, confirmed microarray results for those genes. These results illustrate
      that encapsulation stress is quite different than salt stress in terms of gene
      expression response. Furthermore, a number of hypothetical and unknown proteins
      associated with encapsulation and alcohol stress have been identified with
      implications for improving encapsulation protocols and rationally engineering
      microorganisms for direct biofuel production.

PMID- 22846904
TI  - The antitumor activity of hydrophobin SC3, a fungal protein.
AB  - The use of mushroom extracts has been common practice in traditional medicine for
      centuries, including the treatment of cancer. Proteins called hydrophobins are
      very abundant in mushrooms. Here, it was examined whether they have antitumor
      activity. Hydrophobin SC3 of Schizophyllum commune was injected daily
      intraperitoneally starting 1 day after tumor induction in two tumor mouse models
      (sarcoma and melanoma). SC3 reduced the size and weight of the melanoma
      significantly, but the sarcoma seemed not affected. However, microscopic analysis
      of the tumors 12 days after induction revealed a strong antitumor effect of SC3
      on both tumors. The mitotic activity of the tumor decreased 1.6- (melanoma) to
      2.3-fold (sarcoma), while the vital mass decreased 2.3- (melanoma) to 4.3-fold
      (sarcoma) compared to the control. Treatment did not cause any signs of toxicity.
      Behavior, animal growth, and weight of organs were similar to animals injected
      with vehicle, and no histological abnormalities were found in the organs. In
      vitro cell culture studies revealed no direct cytotoxic effect of SC3 towards
      sarcoma cells, while cytotoxic activity was observed towards melanoma cells at a
      high SC3 concentration. Daily treatment with SC3 did not result in detectable
      levels of anti-SC3 antibodies in the plasma. Instead, a cellular immune response
      was observed. Incubation of spleen cells with SC3 resulted in a 1.5- to 2.5-fold
      increase in interleukin-10 and TNF-alpha mRNA levels. In conclusion, the nontoxic
      fungal hydrophobin SC3 showed tumor-suppressive activity possibly via
      immunomodulation and may be of benefit as adjuvant in combination with
      chemotherapy and radiation.

PMID- 22846905
TI  - [Perfusion computed tomography for diffuse liver diseases].
AB  - CLINICAL/METHODICAL ISSUE: Perfusion computed tomography (CT) has its main
      application in the clinical routine diagnosis of neuroradiological problems.
      STANDARD RADIOLOGICAL METHODS: Polyphase multi-detector spiral computed
      tomography is primarily used in liver diagnostics. METHODICAL INNOVATIONS: The
      use of perfusion CT is also possible for the diagnostics and differentiation of
      diffuse hepatic diseases. PERFORMANCE: The differentiation between cirrhosis and
      cirrhosis-like parenchymal changes is possible. It also helps to detect early
      stages of malignant tumors. ACHIEVEMENTS: However, there are some negative
      aspects, particularly that of radiation exposure. PRACTICAL RECOMMENDATIONS: This
      paper summarizes the technical basics and possible applications of perfusion CT
      in cases of diffuse liver disease and weighs up the advantages and disadvantages
      of the examinations.

PMID- 22846907
TI  - Analysis of four genes involved in the neurodevelopment shows association of
      rs4307059 polymorphism in the cadherin 9/10 region with completed suicide.
AB  - BACKGROUND: We hypothesized that DNA variants affecting neurodevelopment such as
      rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may
      predispose to completed suicide. METHODOLOGY: We used a case-control two-stage
      approach based on a discovery cohort (557 cases and ~550 controls) and
      replication cohort (159 cases and 186 controls). The suicides were ascertained as
      consecutive cases autopsied at the Department of Forensic Medicine, Medical
      University of Warsaw, Poland. RESULTS: In the discovery cohort we found an
      association between suicide and the CC genotype in the rs4307059 polymorphism (OR
      1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among
      suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in
      the pooled cohorts showed that rs4307059 CC was associated with completed suicide
      (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an
      exploratory search for genotype-phenotype correlation we found that males with
      the rs4307059 CC genotype committed suicide earlier than those with CT/TT
      genotypes (p = 0.049). CONCLUSIONS: The CC genotype of rs4307059 located in the
      region between CDH9 and CDH10 is associated with completed suicide in a Polish
      cohort.

PMID- 22846908
TI  - Construction of a stability landscape of the CH3 domain of human IgG1 by
      combining directed evolution with high throughput sequencing.
AB  - One of the most important but still poorly understood issues in protein chemistry
      is the relationship between sequence and stability of proteins. Here, we present
      a method for analyzing the influence of each individual residue on the
      foldability and stability of an entire protein. A randomly mutated library of the
      crystallizable fragment of human immunoglobulin G class 1 (IgG1-Fc) was expressed
      on the surface of yeast, followed by heat incubation at 79 degrees C and
      selection of stable variants that still bound to structurally specific ligands.
      High throughput sequencing allowed comparison of the mutation rate between the
      starting and selected library pools, enabling the generation of a stability
      landscape for the entire CH3 domain of human IgG1 at single residue resolution.
      Its quality was analyzed with respect to (i) the structure of IgG1-Fc, (ii)
      evolutionarily conserved positions and (iii) in silico calculations of the energy
      of unfolding of all variants in comparison with the wild-type protein. In
      addition, this new experimental approach allowed the assignment of functional
      epitopes of structurally specific ligands used for selection [Fc gamma-receptor I
      (CD64) and anti-human CH2 domain antibody] to distinct binding regions in the CH2
      domain.

PMID- 22846909
TI  - The membrane insertase Oxa1 is required for efficient import of carrier proteins
      into mitochondria.
AB  - Oxa1 serves as a protein insertase of the mitochondrial inner membrane that is
      evolutionary related to the bacterial YidC insertase. Its activity is critical
      for membrane integration of mitochondrial translation products and conservatively
      sorted inner membrane proteins after their passage through the matrix. All Oxa1
      substrates identified thus far have bacterial homologs and are of endosymbiotic
      origin. Here, we show that Oxa1 is critical for the biogenesis of members of the
      mitochondrial carrier proteins. Deletion mutants lacking Oxa1 show reduced steady
      state levels and activities of the mitochondrial ATP/ADP carrier protein Aac2. To
      reduce the risk of indirect effects, we generated a novel temperature-sensitive
      oxa1 mutant that allows rapid depletion of a mutated Oxa1 variant in situ by
      mitochondrial proteolysis. Oxa1-depleted mitochondria isolated from this mutant
      still contain normal levels of the membrane potential and of respiratory chain
      complexes. Nevertheless, in vitro import experiments showed severely reduced
      import rates of Aac2 and other members of the carrier family, whereas the import
      of matrix proteins was unaffected. From this, we conclude that Oxa1 is directly
      or indirectly required for efficient biogenesis of carrier proteins. This was
      unexpected, since carrier proteins are inserted into the inner membrane from the
      intermembrane space side and lack bacterial homologs. Our observations suggest
      that the function of Oxa1 is relevant not only for the biogenesis of conserved
      mitochondrial components such as respiratory chain complexes or ABC transporters
      but also for mitochondria-specific membrane proteins of eukaryotic origin.

PMID- 22846910
TI  - Crystal structures of penicillin-binding protein 3 (PBP3) from methicillin
      resistant Staphylococcus aureus in the apo and cefotaxime-bound forms.
AB  - Staphylococcus aureus is a widespread Gram-positive opportunistic pathogen, and a
      methicillin-resistant form (MRSA) is particularly difficult to treat clinically.
      We have solved two crystal structures of penicillin-binding protein (PBP) 3
      (PBP3) from MRSA, the apo form and a complex with the beta-lactam antibiotic
      cefotaxime, and used electrospray mass spectrometry to measure its sensitivity to
      a variety of penicillin derivatives. PBP3 is a class B PBP, possessing an N
      terminal non-penicillin-binding domain, sometimes called a dimerization domain,
      and a C-terminal transpeptidase domain. The model shows a different orientation
      of its two domains compared to earlier models of other class B PBPs and a novel,
      larger N-domain. Consistent with the nomenclature of "dimerization domain", the N
      terminal region forms an apparently tight interaction with a neighboring molecule
      related by a 2-fold symmetry axis in the crystal structure. This dimer form is
      predicted to be highly stable in solution by the PISA server, but mass
      spectrometry and analytical ultracentrifugation provide unequivocal evidence that
      the protein is a monomer in solution.

PMID- 22846911
TI  - Robotic-assisted paraesophageal hernia repair--a case-control study.
AB  - AIMS: The da Vinci(r) telemanipulation system offers a wide range of precise
      movements and 3D visualization with depth perception and magnification effect.
      Such a system could be useful for improving minimally invasive procedures-as in
      the case of large hiatal hernia with paraesophageal involvement (PEH) repair.
      Studies reporting on the robotic-assisted PEH repair are scarce, and a comparison
      to the standard operation techniques is lacking. Therefore, we decided to
      investigate the feasibility and safety of robotic-assisted surgery (RAS) compared
      to conventional laparoscopic (CLS) and open surgery (OS) for the first time.
      METHODS: We investigated 42 patients for the perioperative outcome after PEH
      repair. Twelve patients were operated on with RAS, 17 with CLS, and 13 with OS.
      Operating time, intraoperative blood loss, intra- and postoperative
      complications, mortality, and duration of hospital stay were analyzed in each
      method. RESULTS: On average, operating time in the RAS group was 38 min longer,
      and the intraoperative blood was loss 217 ml lower compared to OS. Both results
      were similar to the CLS group. The intraoperative complication rate was similar
      in all groups. The postoperative complication rate in the RAS group was
      significantly lower than the OS group, though again similar to the CLS group. The
      hospital stay was 5 days shorter in the RAS group than the OS group and once
      again similar to the CLS group. CONCLUSION: The results show that RAS is feasible
      and safe. It appears to be an alternative to OS due to lower intraoperative blood
      loss and potentially fewer postoperative complications, as well as shorter
      hospital stay. Though, RAS is not superior to CLS.

PMID- 22846912
TI  - Genetic variants in miRNAs predict bladder cancer risk and recurrence.
AB  - miRNAs play important roles in numerous cellular processes, including
      development, proliferation, apoptosis, and carcinogenesis. Because altered
      expression and function of miRNAs has been observed in bladder cancer, we
      investigated whether genetic variations in miRNAs are associated with bladder
      cancer risk and prognosis. Using bioinformatics tools, we selected five single
      nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA
      disease associations in a two-stage model, consisting of 1,019 bladder cancer
      cases and 1,182 controls (683 cases and 728 controls in the training set and 336
      cases and 454 controls in the test set). We found that miR-146a rs2910164 C
      allele was associated with significantly decreased risk of bladder cancer in both
      the training and test sets, as well as the combined set [OR = 0.80, 95%
      confidence interval (CI) = 0.71-0.90, P = 2.92 * 10(-4)]. Furthermore, the
      rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence,
      compared with the GG genotype (P = 0.016). Functional analysis revealed that miR
      146a rs2910164 C allele inhibited cell proliferation and significantly
      downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional
      examination of 64 bladder cancer tissues showed that individuals carrying the C
      allele had increased expression levels of miR-146a compared with those carrying
      the G allele (P = 0.010). Taken together, our findings show that miR-146a
      rs2910164 plays an important role in the risk and recurrence of bladder cancer,
      suggesting it may represent a biomarker for risk prevention and therapeutic
      intervention. Further larger and prospective cohorts are needed to validate our
      findings.

PMID- 22846913
TI  - Markers of B-cell activation in relation to risk of non-Hodgkin lymphoma.
AB  - B-cell activation biomarkers have been associated with increased risk of non
      Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar
      association may exist in general populations has not been established. We
      conducted a case-control study within the Women's Health Initiative Observational
      Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30,
      sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL
      diagnosis in 491 cases and 491 controls. Using logistic regression to estimate
      odds ratios, we observed strong associations between NHL and markers for all B
      cell NHL and for major subtypes. Women with marker levels in the highest-versus
      lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5
      fold increased risk of B-NHL. In addition, there were significant trends of risk
      with increasing levels of these markers present. Associations were strongest for
      cases with shortest lag times between blood draw and diagnosis (<3 years).
      However, there were also significant associations for cases with the longest
      prediagnostic lag (9 to 13 years). Taken together, our findings indicate a
      prominent role for B-cell activation among postmenopausal women in the etiology
      of B-cell NHL and/or in processes reflective of early disease development as
      early as 9 years before diagnosis.

PMID- 22846915
TI  - The pi-acceptor effect in the substitution reactions of tridentate N-donor ligand
      complexes of platinum(II): a detailed kinetic and mechanistic study.
AB  - The nucleophilic substitution reactions of complexes [Pt{4'-(2'''-CH(3)-phenyl)
      2,2':6',2''-terpyridine}Cl]CF(3)SO(3), [CH(3)PhPtCl], [Pt{4'-(2'''-CH(3)-phenyl)
      6-(3''-isoquinoyl)-2,2'bipyridine}Cl]SbF(6), [CH(3)PhisoqPtCl], [Pt{2-(2'
      pyridyl)-1,10-phenanthroline}Cl]Cl, [pyPhenPtCl], and [Pt(terpyridine)Cl](+),
      [PtCl] with a series of nucleophiles: thiourea (TU), N,N-dimethylthiourea (DMTU),
      N,N,N,N-tetramethylthiourea (TMTU), I(-), Br(-), and SCN(-) were studied in 0.1 M
      LiCF(3)SO(3) in methanol (in the presence of 10 mM LiCl). The reactivity of the
      investigated complexes follows the order pyPhenPtCl > PtCl > CH(3)PhPtCl >
      CH(3)PhisoqPtCl. The lability of the chloride ligand is dependent on the strength
      of pi-backbonding properties of the spectator ligands around the platinum centre.
      The experimental data is strongly supported by DFT calculations. The dependence
      of the second-order rate constants on concentration of the nucleophiles as well
      as the large negative values reported for the activation entropy (DeltaS(?))
      confirmed an associative mechanism of substitution.

PMID- 22846914
TI  - RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti
      invasive and antitumor activities in breast cancer.
AB  - The Rho-associated kinases ROCK1 and ROCK2 are critical for cancer cell migration
      and invasion, suggesting they may be useful therapeutic targets. In this study,
      we describe the discovery and development of RKI-1447, a potent small molecule
      inhibitor of ROCK1 and ROCK2. Crystal structures of the RKI-1447/ROCK1 complex
      revealed that RKI-1447 is a Type I kinase inhibitor that binds the ATP binding
      site through interactions with the hinge region and the DFG motif. RKI-1447
      suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human
      cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK,
      and S6 kinase at concentrations as high as 10 MUmol/L. RKI-1447 was also highly
      selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress
      fiber formation) following LPA stimulation, but does not affect PAK-meditated
      lamellipodia and filopodia formation following PDGF and Bradykinin stimulation,
      respectively. RKI-1447 inhibited migration, invasion and anchorage-independent
      tumor growth of breast cancer cells. In contrast, RKI-1313, a much weaker analog
      in vitro, had little effect on the phosphorylation levels of ROCK substrates,
      migration, invasion or anchorage-independent growth. Finally, RKI-1447 was highly
      effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse
      model. In summary, our findings establish RKI-1447 as a potent and selective ROCK
      inhibitor with significant anti-invasive and antitumor activities and offer a
      preclinical proof-of-concept that justify further examination of RKI-1447
      suitability as a potential clinical candidate.

PMID- 22846916
TI  - Physiologic consequences of glucose transport and phosphoenolpyruvate node
      modifications in Bacillus subtilis 168.
AB  - The phosphoenolpyruvate (PEP) node is an important carbon distribution point in
      the central metabolic networks; therefore, its modification is a common strategy
      employed for developing microbial production strains. In this study, mutants of
      Bacillus subtilis 168 were generated with deletions of pykA (which encodes
      pyruvate kinase), ptsG (which encodes the glucose-specific IICBA(Glc) component)
      or the ptsGHI operon [which encodes IICBA(Glc), HPr protein and enzyme I from the
      PEP:sugar phosphotransferase system (PTS)]. These modifications caused a
      reduction in the initial rate of [(14)C]-glucose import, corresponding to 10.99,
      2.83 and 0.50% of that found in B. subtilis 168 for strains with inactive pykA,
      ptsG or ptsGHI genes, respectively. Characterization of derivative strains
      lacking 3-dehydroquinate synthase activity showed that inactivation of pykA leads
      to an 8-fold increase in carbon flow to the common aromatic pathway. Quantitative
      real-time PCR analyses of 76 genes from several functional classes revealed a
      carbon starvation transcriptional pattern that includes a partial gluconeogenic
      response and overexpression of genes encoding non-PTS glucose importers in the
      strains lacking functional pykA, ptsG or ptsGHI genes. A transcriptional response
      consistent with pyruvate limitation was also detected, which includes
      upregulation of genes encoding malic enzymes that generate pyruvate from malate.

PMID- 22846917
TI  - Synthesis of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)
      propan-1-ones and their 2-methylene derivatives as potential spermicidal and
      microbicidal agents.
AB  - A series of twenty two derivatives of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4
      yl)-1-(quinolin-4-yl)-propan-1-one and their 2-methylene derivatives were
      synthesized from naturally abundant cinchonine (I). Tartarate salts of these
      compounds were prepared and evaluated for spermicidal activity. The most active
      compounds (24, 27, 34, 36, and 38) showing potent spermicidal activity were
      further evaluated against different strains of Trichomonas vaginalis, for
      antimicrobial activity, in HeLa cell lines for cytotoxicity and against
      Lactobacillus jensenii for eco-safety. The tartarate of 3-(1-pentyl-3-vinyl
      piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one (27) was found to be more active
      than N-9 in spermicidal activity.

PMID- 22846918
TI  - Lentiviral latency in peripheral CD4+ T cells isolated from feline
      immunodeficiency virus-infected cats during the asymptomatic phase is not
      associated with hypermethylation of the proviral promoter.
AB  - Lentiviral latency remains a principal obstacle to curative AIDS therapy.
      Transcriptional repression and latency permits lentiviruses to evade host immune
      responses and antiretroviral drugs. We have established a model of peripheral
      CD4+ T cell lentiviral latency in cats experimentally infected with feline
      immunodeficiency virus (FIV). Multiple mechanisms of lentiviral transcriptional
      repression have been proposed including epigenetic mechanisms resulting in
      promoter hypermethylation and/or chromatin condensation. Methylation of promoter
      associated cytosines in the cytosine-guanine dinucleotide (CpG) has been
      associated with transcriptional repression in both eukaryotic promoters and
      integrated retroviral genomes. Using methylcytosine mapping, we examined the CpG
      methylation patterns in both the 5' and 3' long terminal repeats (LTR) of the FIV
      provirus in peripheral blood mononuclear cells, monocytes and CD4+ T cells
      isolated during the acute and asymptomatic phases of infection. Here we report no
      evidence that proviral promoter hypermethylation is associated with lentiviral
      latency in peripheral CD4+ T cells and monocytes obtained from experimentally FIV
      infected cats.

PMID- 22846920
TI  - A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can
      gradually escape under the selection pressure of neutralizing human plasma.
AB  - Viral replication and neutralization of hepatitis C viruses (HCV) have been
      studied using the infectious molecular clone JFH-1. By passaging JFH-1 in
      hepatoma cells in the absence or presence of HCV neutralizing antibodies (nAbs),
      we investigated the molecular mechanisms of cell-culture adaptation and
      sensitivity to nAbs. The cell culture-adapted JFH-1 virus (JFH-1-CA) became more
      sensitive to nAbs than its parental virus. Sequence analysis revealed that the
      predominant viruses in the JFH-1-CA population carried two mutations in their
      envelopes (I414T and V293A). Plasma that could neutralize JFH-1-CA was found in 2
      of 7 HCV-infected individuals who have cleared the virus in blood. Plasma 226233
      with a higher 50% neutralization titer was used for in vitro selection of
      neutralization resistant viruses. Under the increasing selection pressure of
      plasma 226233, the neutralizing sensitivity of JFH-1-CA decreased gradually. Two
      mutations (T414I and P500S) in envelope were found in all but one sequenced
      clones in the viral population after eight rounds of selection. Interestingly,
      the cell-culture adapted mutation I414T reverted back to the wild-type residue
      (I414) under the selection pressure. By introducing mutations at positions 414
      and 500 into the JFH-1 clone, we confirmed that the T414I mutation alone can
      confer neutralization resistance. The results of this current study suggest that
      nAbs are present in a subset of HCV-infected individuals who have cleared the
      virus in blood. Our data also provide the first evidence that, the E2 residue
      P500, located within a previously identified highly conserved polyclonal epitope,
      may be a target for neutralizing antibodies present in individual who have
      spontaneously resolved the HCV infection.

PMID- 22846919
TI  - Identification of a high affinity nucleocapsid protein binding element from the
      bovine leukemia virus genome.
AB  - Retroviral genome recognition is mediated by interactions between the
      nucleocapsid (NC) domain of the virally encoded Gag polyprotein and cognate RNA
      packaging elements that, for most retroviruses, appear to reside primarily within
      the 5'-untranslated region (5'-UTR) of the genome. Recent studies suggest that a
      major packaging determinant of bovine leukemia virus (BLV), a member of the human
      T-cell leukemia virus (HTLV)/BLV family and a non-primate animal model for HTLV
      induced leukemogenesis, resides within the gag open reading frame. We have
      prepared and purified the recombinant BLV NC protein and conducted
      electrophoretic mobility shift and isothermal titration calorimetry studies with
      RNA fragments corresponding to these proposed packaging elements. The gag-derived
      RNAs did not exhibit significant affinity for NC, suggesting an alternate role in
      packaging. However, an 83-nucleotide fragment of the 5'-UTR that resides just
      upstream of the gag start codon binds NC stoichiometrically and with high
      affinity (K(d)=136+/-21 nM). These nucleotides were predicted to form tandem
      hairpin structures, and studies with smaller fragments indicate that the NC
      binding site resides exclusively within the distal hairpin (residues G369-U399,
      K(d)=67+/-8 nM at physiological ionic strength). Unlike all other structurally
      characterized retroviral NC binding RNAs, this fragment is not expected to
      contain exposed guanosines, suggesting that RNA binding may be mediated by a
      previously uncharacterized mechanism.

PMID- 22846921
TI  - Identification of common human host genes involved in pathogenesis of different
      rotavirus strains: an attempt to recognize probable antiviral targets.
AB  - Although two rotavirus vaccines have been licensed and approved by WHO and FDA;
      other parallel therapeutic strategies are needed to reduce the mortality and
      morbidity of rotavirus induced diarrhea worldwide. Since rotaviruses utilize the
      host cell machinery for their replication, study was initiated to identify host
      proteins which positively regulate rotavirus infection. To overcome the possible
      variations in host response due to existence of large variety of genotypes and
      human-animal reassortants, the total gene expression profile of HT29 cells
      infected with either simian (SA11) or bovine (A5-13) or human (Wa) rotavirus
      strains was analyzed using genome microarrays. Even though cells infected with
      human strain revealed some differences compared to the viruses of animal origin,
      131 genes were similarly induced by all three strains. Genes involved in innate
      immune response, stress response, apoptosis and protein metabolism were induced
      by all viral strains. Results were validated by immunoblotting or RT-PCR. Role of
      some host genes in rotavirus infection was analyzed by using specific siRNAs.

PMID- 22846922
TI  - Tuning fifth-order aberrations in a quadrupole-octupole corrector.
AB  - The resolution of conventional electron microscopes is usually limited by
      spherical aberration. Microscopes equipped with aberration correctors are then
      primarily limited by higher order, chromatic, and misalignment aberrations. In
      particular the Nion third-order aberration correctors installed on machines with
      a low energy spread and possessing sophisticated alignment software were limited
      by the uncorrected fifth-order aberrations. Here we show how the Nion fifth-order
      aberration corrector can be used to adjust and reduce some of the fourth- and
      fifth-order aberrations in a probe-corrected scanning transmission electron
      microscope.

PMID- 22846923
TI  - Explaining reaction mechanisms using the dual descriptor: a complementary tool to
      the molecular electrostatic potential.
AB  - The intrinsic reactivity of cyanide when interacting with a silver cation was
      rationalized using the dual descriptor (DD) as a complement to the molecular
      electrostatic potential (MEP) in order to predict interactions at the local
      level. It was found that DD accurately explains covalent interactions that cannot
      be explained by MEP, which focuses on essentially ionic interactions. This
      allowed the rationalization of the reaction mechanism that yields silver cyanide
      in the gas phase. Other similar reaction mechanisms involving a silver cation
      interacting with water, ammonia, and thiosulfate were also explained by the
      combination of MEP and DD. This analysis provides another example of the
      usefulness of DD as a tool for gaining a deeper understanding of any reaction
      mechanism that is mainly governed by covalent interactions.

PMID- 22846924
TI  - Structural and chemical basis for enhanced affinity to a series of mycobacterial
      thymidine monophosphate kinase inhibitors: fragment-based QSAR and QM/MM docking
      studies.
AB  - Tuberculosis (TB) still remains one of the most deadly infectious diseases.
      Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) has emerged as
      an attractive molecular target for the design of a novel class of anti-TB agents
      since blocking it will affect the pathways involved in DNA replication. Aiming at
      shedding some light on structural and chemical features that are important for
      the affinity of thymidine derivatives to TMPKmt, we have employed a special
      fragment-based method to develop robust quantitative structure-activity
      relationship models for a large and chemically diverse series of thymidine-based
      analogues. Significant statistical parameters (r2= 0.94, q2= 0.76, r2pred= 0.89)
      were obtained, indicating the reliability of the hologram QSAR model in
      predicting the biological activity of untested compounds. The 2D model was then
      used to predict the potency of an external test set, and the predicted values
      obtained from the HQSAR model were in good agreement with the experimental
      results. We have accordingly designed novel TMPKmt inhibitors by utilizing the
      fragments proposed by HQSAR analysis and predicted with good activity in the
      developed models. The new designed compounds also presented drug-like
      characteristics based on Lipinski's rule of 5. The generated molecular
      recognition patterns gathered from the HQSAR analysis combined with quantum
      mechanics/molecular mechanics (QM/MM) docking studies, provided important
      insights into the chemical and structural basis involved in the molecular
      recognition process of this series of thymidine analogues and should be useful
      for the design of new potent anti-TB agents.

PMID- 22846925
TI  - Anion recognition by azophenol thiourea-based chromogenic sensors: a combined DFT
      and molecular dynamics investigation.
AB  - The relative binding affinities of several anions towards 2-nitroazophenol
      thiourea-based receptors were studied using density functional theory (DFT) in
      the gas phase and in chloroform solvent via PCM calculations. Both receptors have
      five distinctive NH and OH hydrogen donor atoms. All receptor-anion complexes are
      characterized by five intermolecular hydrogen bonds. The binding free energies
      are strongly influenced by a dielectric medium, and the solvation effect alters
      the trend of anion binding to the receptor. The calculated order of anion binding
      affinity for the receptor in chloroform, H2PO4->AcO->F->Cl->HSO4->NO3-, is in
      excellent accord with experimental findings. The overall order of binding
      affinity is attributed to the basicity of the anion, the effect of solvation, and
      the number of proton acceptors available. Calculations of the NMR and UV-vis
      spectra strongly support the experimental characterization of the receptor-anion
      complexes. Explicit solvent molecular dynamics simulations of selected receptor
      anion complexes were also carried out. Analysis of the structural descriptors
      revealed that the anions were strongly bound within the binding pocket via
      hydrogen-bonding interactions to the five receptor protons throughout the
      simulation.

PMID- 22846926
TI  - Performance comparison of computational methods for modeling alpha-helical
      structures.
AB  - Geometry optimization results are reported for secondary structural elements of
      small proteins and polypeptides. Emphasis is placed on how well molecular
      mechanics as well as semiempirical, ab initio, and density functional methods
      describe alpha-helical and related structures in purely theoretical models
      (Gly10, Ile10) as well as in realistic models (an alpha-helical region of
      calmodulin, and the complete structure of a small protein). Many of the methods
      examined here were found to provide unsatisfactory descriptions of the hydrogen
      bonding interactions within polypeptide-type structures, as the alpha-helical
      canonical secondary structure motif was not reproduced accurately. Ab initio and
      DFT methods provided reasonable results only when solvation models were included,
      although Hartree-Fock failed even with solvation in one of the test cases; among
      the semiempirical methods, one of the PM6 implementations performed very well.

PMID- 22846927
TI  - Analyzing In Vivo Metabolite-Protein Interactions By Large-Scale Systematic
      Analyses.
AB  - Metabolites interact with proteins in vivo in various ways other than enzymatic
      reactions. Profiling of such interactions may help disclose unknown molecular
      mechanisms that regulate protein functions, and provide potential targets for
      disease treatment. Here we describe a procedure for systematic analyses of
      metabolite-protein interactions in vivo. This procedure couples protein affinity
      purification and mass spectrometry to identify metabolite-protein interactions.
      The primary effort can be completed within one day and scaled to process hundreds
      of samples in a batch. Originally developed in yeast, the same principle and
      protocol can be adapted to other organisms.

PMID- 22846929
TI  - Glucocorticoid sensitivity of T-cell lymphoblastic leukemia/lymphoma is
      associated with glucocorticoid receptor-mediated inhibition of Notch1 expression.

PMID- 22846931
TI  - It matters: the case for advocacy.

PMID- 22846932
TI  - A brief history of the founding of the Eastern Association for the Surgery of
      Trauma.

PMID- 22846933
TI  - The trauma of politics: a surgeon general's perspective.

PMID- 22846934
TI  - The National Trauma Triage Protocol: can this tool predict which patients with
      trauma will benefit from helicopter transport?
AB  - BACKGROUND: Helicopter transport (HT) is an important component of American
      trauma care, but prospectively identifying patients that would benefit from this
      resource remains difficult. The objective of this study was to assess the role of
      the National Trauma Triage Protocol (NTTP) in selecting patients that would
      benefit from HT. METHODS: Subjects transported by HT or ground transport from the
      scene of injury in 2007 were identified using the National Trauma Databank
      version 8. Criteria from the stepwise NTTP available in the data set were
      collected including physiologic data, anatomic injuries identified by DRG
      International Classification of Diseases-9th Rev. codes, and age. Subgroups of
      patients who met specific triage criteria were evaluated using logistic
      regression to determine if transport modality was an independent predictor of
      survival after controlling for demographics, injury severity, prehospital time,
      and presence of other NTTP triage criteria. Standard test characteristics were
      calculated for each criterion to predict trauma center need (TCN). The
      performance of triage criteria to predict TCN was compared between the groups
      using independent receiver operating characteristic area under the curve
      analysis. RESULTS: There were 258,387 subjects transported either by helicopter
      (16%) or by ground (84%). HT subjects were more severely injured (mean [SD],
      Injury Severity Score, 15.9 [12] vs. 10.2 [10], p < 0.01). Logistic regression
      identified HT as an independent predictor of survival in subjects with a subset
      of triage criteria, including penetrating injury, GCS<14, RR<10 or >29 breaths
      per minute, and age>55 years. Each criterion previously mentioned was
      significantly more predictive of TCN in the HT group than in the ground transport
      group (p < 0.01). CONCLUSION: Patients who meet certain triage criteria in the
      field seem to have an independent survival benefit if transported to a trauma
      center by helicopter. Furthermore, these criteria are highly specific and more
      reliably predict TCN in the HT group. The specific triage criteria listed
      previously should be carefully considered when developing policies for scene
      helicopter use in the trauma setting.

PMID- 22846935
TI  - Has TRISS become an anachronism? A comparison of mortality between the National
      Trauma Data Bank and Major Trauma Outcome Study databases.
AB  - BACKGROUND: The Trauma and Injury Severity Score (TRISS) has been the approach to
      trauma outcome prediction during the past 20 years and has been adopted by many
      commercial registries. Unfortunately, its survival predictions are based upon
      coefficients that were derived from a data set collected in the 1980s and updated
      only once using a data set collected in the early 1990s. We hypothesized that the
      improvements in trauma care during the past 20 years would lead to improved
      survival in a large database, thus making the TRISS biased. METHODS: The TRISSs
      from the Pennsylvania statewide trauma registry (Collector, Digital Innovations)
      for the years 1990 to 2010. Observed-to-expected mortality ratios for each year
      of the study were calculated by taking the ratio of actual deaths (observed
      deaths, O) to the summation of the probability of mortality predicted by the
      TRISS taken over all patients (expected deaths, E). For reference, O/E ratio
      should approach 1 if the TRISS is well calibrated (i.e., has predictive
      accuracy). RESULTS: There were 408,489 patients with complete data sufficient to
      calculate the TRISSs. There was a significant trend toward improved outcome
      (i.e., decreasing O/E ratio; nonparametric test of trend, p < 0.001) over time in
      both the total population and the blunt trauma subpopulation. In the penetrating
      trauma population, there was a trend toward improved outcome (decreasing O/E
      ratio), but it did not quite reach significance (nonparametric test of trend p =
      0.073). CONCLUSION: There is a steady trend toward improved O/E survival in the
      Pennsylvania database with each passing year, suggesting that the TRISS is
      drifting out of calibration. It is likely that improvements in care account for
      these changes. For the TRISS to remain an accurate outcome prediction model, new
      coefficients would need to be calculated periodically to keep up with trends in
      trauma care. This requirement for occasional updating is likely to be a
      requirement of any trauma prediction model, but because many other deficiencies
      in the TRISS have been reported, we think that rather than updating the TRISS, it
      would be more productive to replace the TRISS with a modern statistical model.

PMID- 22846936
TI  - Still making the case against prehospital intubation: a rat hemorrhagic shock
      model.
AB  - BACKGROUND: Prehospital intubation does not appear to result in a survival
      advantage for patients experiencing penetrating trauma; yet, there is still
      resistance to the practice of "scoop and run" to speed access to advanced care.
      An animal model was used to determine whether intubation provides a survival
      advantage during potentially lethal hemorrhage. METHODS: The carotid arteries of
      Sprague-Dawley rats were cannulated, and mean arterial pressure (MAP) was
      measured. One group of animals (n = 10) was intubated and placed on a ventilator,
      whereas the other (n = 9) was administered with 100% oxygen via nose cone. Rats
      were exsanguinated to a MAP of 40 mm Hg and then bled periodically to maintain a
      MAP between 40 mm Hg and 45 mm Hg. The primary end-point was time until death.
      Secondary end-points included lactic acid and base excess levels measured in
      blood collected at 30-minute intervals after inducing shock. RESULTS: There was
      no significant difference in time until death between the intubated and nose cone
      groups (85.5 vs. 93.3 minutes, p = 0.60). Intubated animals had higher lactic
      acid levels at 90 minutes (6.1 vs. 3.5 mmol/L; p = 0.02) and 120 minutes (7.7 vs.
      2.6 mmol/L, p = 0.03) after the initiation of shock. In addition, intubated
      animals had worse base excess at 90 minutes (-13.5 vs. -7.9 mmol/L, p = 0.04).
      CONCLUSION: Intubation does not result in a survival advantage in this rat model
      of hemorrhagic shock. Positive pressure ventilation may cause decreased venous
      return and accentuate end-organ hypoperfusion. Large animal studies are needed to
      further investigate these findings.

PMID- 22846937
TI  - Vagal nerve stimulation modulates gut injury and lung permeability in trauma
      hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock is known to disrupt the gut barrier leading to end
      organ dysfunction. The vagus nerve can inhibit detrimental immune responses that
      contribute to organ damage in hemorrhagic shock. Therefore, we explored whether
      stimulation of the vagus nerve can protect the gut and recover lung permeability
      in trauma-hemorrhagic shock (THS). METHODS: Male Sprague-Dawley rats were
      subjected to left cervical vagus nerve stimulation at 5 V for 10 minutes. The
      right internal jugular and femoral artery were cannulated for blood withdrawal
      and blood pressure monitoring, respectively. Animals were then subjected to
      hemorrhagic shock to a mean arterial pressure between 30 mm Hg and 35 mm Hg for
      90 minutes then reperfused with their own whole blood. After observation for 3
      hours, gut permeability was assessed with fluorescein dextran 4 in vivo
      injections in a ligated portion of distal ileum followed by Evans blue dye
      injection to assess lung permeability. Pulmonary myeloperoxidase levels were
      measured and compared. RESULTS: Vagal nerve stimulation abrogated THS-induced
      lung injury (mean [SD], 8.46 [0.36] vs. 4.87 [0.78]; p < 0.05) and neutrophil
      sequestration (19.39 [1.01] vs. 12.83 [1.16]; p < 0.05). Likewise, THS gut
      permeability was reduced to sham levels. CONCLUSION: Neuromodulation decreases
      injury in the THS model as evidenced by decreased gut permeability as well as
      decreased lung permeability and pulmonary neutrophil sequestration in a rat
      model.

PMID- 22846939
TI  - Similar effects of hypertonic saline and mannitol on the inflammation of the
      blood-brain barrier microcirculation after brain injury in a mouse model.
AB  - BACKGROUND: There has been substantial debate regarding the efficacy of
      hypertonic saline (HTS) versus mannitol (MTL) in treating moderate and severe
      traumatic brain injury (TBI). HTS blunts polymorphonuclear neutrophil (PMN) and
      endothelial cell (EC) activation and reduces tissue edema after resuscitated
      shock in systemic microvascular beds. MTL also modulates PMN activation markers.
      It remains unknown if either of these osmotherapies exert similar anti
      inflammatory effects along the blood-brain barrier (BBB). We hypothesized that
      HTS, as compared with MTL, would more greatly reduce PMN-EC interactions, thereby
      reducing BBB permeability and tissue edema after simulated TBI. METHODS: CD1 male
      mice (25-30 g) underwent craniotomy and window placement for observation of in
      vivo PMN-EC interactions in pial venules using intravital video microscopy. TBI
      was simulated through local suffusion of the brain surface with interleukin 1beta
      (100 ng/0.1 mL). Animals were randomized to receive a single, equiosmolar,
      intravenous dose of 20% MTL or 5% HTS after injury. Live microcirculatory footage
      was obtained every 15 minutes for 2 hours, after which fluorescent-labeled
      albumin was administered to assess microvascular permeability. PMN rolling and
      adhesion and macromolecular leakage were analyzed offline by a blinded observer
      and postmortem brain and lung edema assessed by wet-to-dry ratios. Student's t
      test and Mann-Whitney U test determined significance (p <= 0.05). RESULTS:
      Neither osmotherapy resulted in significant differences in PMN rolling or
      adhesion; however, both trended higher in HTS. Similarly, vessel permeability did
      not differ between groups but also trended higher with HTS. In contrast, brain
      and lung edema was greater in MTL than HTS as compared with controls (p = 0.05).
      CONCLUSION: MTL and HTS have indistinguishable effects on PMN-EC interactions in
      the brain after simulated TBI. Additional studies are needed to determine if
      either osmotherapy has more subtle effects on BBB PMN-EC interactions after
      injury exerting a potential clinical advantage.

PMID- 22846938
TI  - Is the sympathetic system involved in shock-induced gut and lung injury?
AB  - BACKGROUND: beta-blockade (BB) has been shown to prevent bone marrow (BM)
      dysfunction after trauma and hemorrhagic shock (HS). The impact of the
      sympathetic system and the role of BB on shock-induced distant organ injury is
      not known. This study will determine if BB has systemic effects and can diminish
      gut and lung injury after trauma and HS. METHODS: Male Sprague-Dawley rats were
      subjected to lung contusion (LC) followed by 45 minute of HS. Animals (n = 6 per
      group) were then randomized to either receive propranolol (LCHS + BB) immediately
      after resuscitation or not (LCHS). Gut permeability was evaluated in by diffusion
      of Mr 4,000 of fluorescein dextran (FD4) from a segment of small bowel into
      peripheral blood. Villous injury and lung injury were graded histologically by a
      blinded reader. Plasma-mediated effects of BB were evaluated in vitro by an
      assessment of BM progenitor growth. RESULTS: Animals undergoing LCHS had
      significantly higher plasma levels of FD4 compared with control animals (mean
      [SEM], 2.8 [0.4] ug/mL vs. 0.8 [0.2] ug/mL). However, animals receiving BB had a
      significant reduction in plasma FD4 compared with the LCHS group. With the use of
      BB after LCHS, both ileal and lung injury scores were similar to control. In
      addition, BM progenitor growth was inhibited by the addition of LCHS plasma, and
      LCHS + BB plasma showed no inhibition of BM progenitor growth. CONCLUSION:
      Propranolol can protect against the detrimental effects of trauma and HS on gut
      permeability, villous, and lung injury. The effects of BB are likely systemic and
      appear to be mediated through plasma. BB likely blunts the exaggerated
      sympathetic response after shock and injury. Propranolol's reduction of both BM
      dysfunction and distant organ injury further demonstrates the importance of the
      sympathetic nervous system and its role in potentiating end organ dysfunction
      after severe trauma.

PMID- 22846940
TI  - Debunking the survival bias myth: characterization of mortality during the
      initial 24 hours for patients requiring massive transfusion.
AB  - BACKGROUND: Controversy surrounds the optimal ratios of blood (packed red blood
      cell [PRBC]), plasma (fresh frozen plasma [FFP]) and platelet (PLT) use for
      patients requiring massive transfusion (MT) owing to possible survival bias in
      previous studies. We sought to characterize mortality during the first 24 hours
      while controlling for time varying effects of transfusion to minimize survival
      bias. METHODS: Data were obtained from a multicenter prospective cohort study of
      adults with blunt injury and hemorrhagic shock. MT was defined as 10 U of PRBC or
      more over 24 hours. High FFP/PRBC (>=1:1.5) and PLT/PRBC (>=1:9) ratios at 6, 12,
      and 24 hours were compared with low ratio groups. Cox proportional hazards
      regression was used to determine the independent association of high versus low
      ratios with mortality at 6, 12, and 24 hours while controlling for important
      confounders. Cox proportional hazards regression was repeated with FFP/PRBC and
      PLT/PRBC ratios analyzed as time-dependent covariates to account for fluctuation
      over time. Mortality for more than 24 hours was treated as survival. RESULTS: In
      the MT cohort (n = 604), initial base deficit, lactate, and international
      normalized ratio were similar across high and low ratio groups. High 6-hour
      FFP/PRBC and PLT/PRBC ratios were independently associated with a reduction in
      mortality risk at 6, 12, and 24 hours (hazard ratio [HR] range, 0.20-0.41, p <
      0.05). These findings were consistent for 12-hour and 24-hour ratios. When
      analyzed as time-dependent covariates, a high FFP/PRBC ratio was associated with
      a 68% (HR, 0.32; 95% confidence interval [CI], 0.12-0.87, p = 0.03) reduction in
      24-hour mortality, and a high PLT/PRBC ratio was associated with a 96% (HR, 0.04;
      95% CI, 0.01-0.94, p = 0.04) reduction in 24-hour mortality. Subgroup analysis
      revealed that a high 1:1 ratio (>=1:1.5) had a significant 24-hour survival
      benefit relative to a high 1:2 (1:1.51-1:2.50) ratio group at both 6 hours (HR,
      0.19; 95% CI, 0.03-0.86, p = 0.03) and 24 hours (HR, 0.25; 95% CI, 0.06-0.95, p =
      0.04), suggesting a dose-response relationship. A high FFP/PRBC or PLT/PRBC ratio
      was not associated with development of multiple-organ failure, nosocomial
      infection, or adult respiratory distress syndrome in a 28-day Cox proportional
      hazards regression. CONCLUSION: Despite similar degrees of early shock and
      coagulopathy, high FFP/PRBC and PLT/PRBC ratios are associated with a survival
      benefit as early as 6 hours and throughout the first 24 hours, even when time
      dependent fluctuations of component transfusion are accounted for. This suggests
      that the observed mortality benefit associated with high component transfusion
      ratios is unlikely owing to survivor bias and that early attainment of high
      transfusion ratios may significantly lower the risk of mortality in MT patients.

PMID- 22846941
TI  - Hyperfibrinolysis at admission is an uncommon but highly lethal event associated
      with shock and prehospital fluid administration.
AB  - BACKGROUND: Hyperfibrinolysis (HF) has been reported to occur in a range of 2% to
      34% of trauma patients. Using rapid thromboelastography (r-TEG), we hypothesized
      that HF is (1) rarely present at admission on patients with severe injury and (2)
      associated with crystalloid hemodilution. To further strengthen this hypothesis,
      we created an in vitro hemodilution model to improve our mechanistic
      understanding of the early HF. METHODS: The trauma registry was queried for
      patients who were our highest-level trauma activations and admitted directly from
      the scene (October 2009-October 2010). HF was defined as more than 7.5% amplitude
      reduction 30 minutes after maximal amplitude (LY30). Using r-TEG, we then created
      an in vitro hemodilution model (0.9% NS) with and without tissue injury (addition
      of tissue factor and tissue plasminogen activator) to identify crystalloid
      volumes and injury needed to achieve specific LY30 values. RESULTS: Admission r
      TEG values were captured on 1996 consecutive admissions. Only 41 patients (2%)
      had HF at admission r-TEG. The groups were similar in demographics. Compared with
      patients without HF, the HF group had more prehospital crystalloid (1.5 vs. 0.5
      L), higher median Injury Severity Score (25 vs. 16), greater admission base
      deficit (20 vs. 2), and higher mortality (76% vs. 10%); all p < 0.001.
      Controlling for Injury Severity Score and base deficit on arrival, prehospital
      fluid was associated with a significant increase in likelihood of HF. In fact,
      each additional liter of crystalloid was associated with a 15% increased odds of
      HF. The in vitro model found that hemodilution to 15% of baseline and tissue
      factor + tissue plasminogen activator was required to achieve an LY30 of 50%.
      CONCLUSION: Although uncommon immediately after injury, HF is associated with
      prehospital crystalloid administration and shock at admission and is highly
      lethal. Our in vitro model confirms that tissue injury and significant
      crystalloid hemodilution result in severe and immediate HF.

PMID- 22846942
TI  - Evaluation for intra-abdominal injury in children after blunt torso trauma: can
      we reduce unnecessary abdominal computed tomography by utilizing a clinical
      prediction model?
AB  - BACKGROUND: Blunt trauma is a leading cause of morbidity and mortality in
      children. Despite the potential for malignancy, increased cost, limited small
      bowel injury detection sensitivity, and the low incidence of injury requiring
      operative intervention, the use of computed tomographic (CT) scan in pediatric
      blunt trauma evaluation remains common. Previous studies suggest that a clinical
      model using examination and laboratory data may help predict intra-abdominal
      injuries (IAIs) and potentially limit unnecessary CT scans in children. METHODS:
      A retrospective chart review of all blunt "trauma alerts" for patients younger
      than 16 years during an 18-month period was performed at a Level I trauma center.
      Clinical factors, which might predict blunt IAI (hemodynamics, abdominal
      examination, serology, and plain radiographs), and potential limitations to
      performing a reliable abdominal examination (altered mental status, young age)
      were reviewed. A previously defined clinical prediction model based on six high
      risk clinical variables for blunt IAI (hypotension, abnormal abdominal
      examination, elevated aspartate aminotransferase, elevated amylase, low
      hematocrit, and heme-positive urinalysis) was applied to each patient. RESULTS:
      Of the 125 "trauma alert" patients who sustained blunt trauma during the study
      period, 97 underwent abdominal CT scan, with only 15 identified as IAI. Our
      prediction rule would have identified 16 of 17 patients with IAI (SE, 94%) as
      high-risk and missed only 1 patient (grade I spleen laceration, which did not
      require operation) (negative predictive value, 99%). Of the 83 patients with no
      risk factors for IAI based on the prediction rule, 54 underwent a negative
      abdominal CT scan. Of these 54 patients, only 22 had a potential limitation to a
      reliable abdominal examination. Application of our prediction rule could have
      prevented unnecessary CT scan in at least 32 patients (33%) during an 18-month
      period. CONCLUSION: Use of a prediction model based on high-risk variables for
      IAI may decrease cost and radiation exposure by reducing the number of abdominal
      CT scans in children being evaluated for blunt abdominal trauma.

PMID- 22846943
TI  - A multicenter prospective analysis of pediatric trauma activation criteria
      routinely used in addition to the six criteria of the American College of
      Surgeons.
AB  - BACKGROUND: The American College of Surgeons has defined six minimum activation
      criteria (ACS-6) for the highest level of trauma activations at trauma centers.
      The verification criteria also allow for the inclusion of additional criteria at
      the institution's discretion. The purpose of this prospective multicenter study
      was to evaluate the ACS-6 as well as commonly used activation criteria to
      evaluate overtriage and undertriage rates for pediatric trauma team activation.
      METHODS: Data were prospectively collected at nine pediatric trauma centers to
      examine 29 commonly used activation criteria. Patients meeting any of these
      criteria were evaluated for the use of high-level trauma resuscitation resources
      according to an expert consensus list. Patients requiring a resource but not
      meeting any activation criteria were included to evaluate undertriage rates.
      RESULTS: During the 1-year study, a total of 656 patients were enrolled with a
      mean age of 8 years, a median Injury Severity Score of 14, and mortality of 11%.
      Using all criteria, 55% of patients would have been overtriaged and 9% would have
      been undertriaged. If only the ACS-6 were used, 24% of patients would have been
      overtriaged and 16% would have been undertriaged. Among activation criteria with
      more than 10 patients, those most predictive of using a high-level resource were
      a gunshot wound to the abdomen (92%), blood given before arrival (83%), traumatic
      arrest (83%), tachycardia/poor perfusion (83%), and age-appropriate hypotension
      (77%). The addition of tachycardia/poor perfusion and pretrauma center
      resuscitation with greater than 40 mL/kg results in eight criteria with an
      overtriage of 39% and an undertriage of 10.5%. CONCLUSION: The ACS-6 provides a
      reliable overtriage or undertriage rate for pediatric patients. The inclusion of
      two additional criteria can further improve these rates while maintianing a
      simplified triage list for children.

PMID- 22846944
TI  - Insertion of central venous catheters induces a hypercoagulable state.
AB  - BACKGROUND: Central venous catheters (CVCs) increase the risk of venous
      thromboembolism. We have previously demonstrated that pulmonary artery catheters
      are associated with a hypercoagulable state in an animal model and in patients.
      The purpose of this study is to determine whether the insertion of a CVC is
      associated with a similar response. METHODS:  ANIMAL: 7F femoral artery catheters
      were placed in healthy anesthetized swine (N = 16). Serial arterial blood samples
      were drawn immediately before and after an 8.5F jugular vein CVC and then for 3
      hours after CVC removal. Samples were analyzed using kaolin-activated
      thromboelastography (TEG) at precisely 2 minutes. Human: An institutional review
      board-approved prospective observational trial was conducted, with informed
      consent, in patients with critical illness (N = 8) at a Level I trauma center.
      Blood was drawn from indwelling arterial catheters immediately before and 60
      minutes after CVC insertion. Samples were stored in sodium citrate for 15 minutes
      before TEG. Routine and special coagulation tests were performed on stored
      samples in the hospital pathology laboratory. RESULTS: Insertion of a CVC
      decreased TEG clotting time (R) by 55% in swine and by 29% in humans (p < 0.001
      and 0.019, respectively). Initial clot formation time (K) was reduced by 41% in
      swine and by 36% in humans (p = 0.003 and 0.019). Fibrin cross-linking (alpha)
      was accelerated by 28% in swine and by 17% in humans (p = 0.007 and 0.896), but
      overall clot strength (maximum amplitude) was not affected. There was no change
      in routine or special coagulation factors, including von Willebrand factor,
      antithrombin III, prothrombin time, international normalized ratio, or activated
      partial thromboplastin time. In animals, the hypercoagulable TEG response was
      persistent for 3 hours after CVC removal and was prevented by pretreatment with
      enoxaparin (n = 4) but not heparin (n = 2). CONCLUSION: In healthy swine and
      patients with critical illness, a systemic hypercoagulable state occurred after
      CVC insertion, and this may partially account for an increased risk of venous
      thromboembolism. However, because the sample size was small and not powered to
      detect changes in coagulation proteins, no inferences can be made about the
      mechanism for the hypercoagulable response.

PMID- 22846945
TI  - Early stabilizing alveolar ventilation prevents acute respiratory distress
      syndrome: a novel timing-based ventilatory intervention to avert lung injury.
AB  - BACKGROUND: Established acute respiratory distress syndrome (ARDS) is often
      refractory to treatment. Clinical trials have demonstrated modest treatment
      effects, and mortality remains high. Ventilator strategies must be developed to
      prevent ARDS. HYPOTHESIS: Early ventilatory intervention will block progression
      to ARDS if the ventilator mode (1) maintains alveolar stability and (2) reduces
      pulmonary edema formation. METHODS: Yorkshire pigs (38-45 kg) were anesthetized
      and subjected to a "two-hit" ischemia-reperfusion and peritoneal sepsis. After
      injury, animals were randomized into two groups: early preventative ventilation
      (airway pressure release ventilation [APRV]) versus nonpreventative ventilation
      (NPV) and followed for 48 hours. All animals received anesthesia, antibiotics,
      and fluid or vasopressor therapy as per the Surviving Sepsis Campaign. Titrated
      for optimal alveolar stability were the following ventilation parameters: (1) NPV
      group--tidal volume, 10 mL/kg + positive end-expiratory pressure - 5 cm/H2O
      volume-cycled mode; (2) APRV group--tidal volume, 10 to 15 mL/kg; high pressure,
      low pressure, time duration of inspiration (Thigh), and time duration of release
      phase (Tlow). Physiological data and plasma were collected throughout the 48-hour
      study period, followed by BAL and necropsy. RESULTS: APRV prevented the
      development of ARDS (p < 0.001 vs. NPV) by PaO2/FIO2 ratio. Quantitative
      histological scoring showed that APRV prevented lung tissue injury (p < 0.001 vs.
      NPV). Bronchoalveolar lavage fluid showed that APRV lowered total protein and
      interleukin 6 while preserving surfactant proteins A and B (p < 0.05 vs. NPV).
      APRV significantly lowered lung water (p < 0.001 vs. NPV). Plasma interleukin 6
      concentrations were similar between groups. CONCLUSION: Early preventative
      mechanical ventilation with APRV blocked ARDS development, preserved surfactant
      proteins, and reduced pulmonary inflammation and edema despite systemic
      inflammation similar to NPV. These data suggest that early preventative
      ventilation strategies stabilizing alveoli and reducing pulmonary edema can
      attenuate ARDS after ischemia-reperfusion and sepsis.

PMID- 22846946
TI  - Human microparticles generated during sepsis in patients with critical illness
      are neutrophil-derived and modulate the immune response.
AB  - BACKGROUND: Microparticles (MPs) are 0.3 MUm to 1.0 MUm vesicles generated after
      cell activation or apoptosis that may play a role in the pathophysiology of
      sepsis. We sought to elucidate the role of MPs in patients with critical illness
      and hypothesized that MPs are generated at the site of inflammation and can
      modulate the immune response. METHODS: Surgical patients with critical illness
      with ongoing sepsis were enrolled from the intensive care unit of an urban, Level
      I trauma center from March to June 2011. Abdominal washings and bronchoalveolar
      lavage fluid were collected from sites of inflammation. MPs were isolated using
      differential centrifugation, then characterized by flow cytometry. Immunologic
      assays were conducted by incubating neutrophil-derived MPs (NDMPs) with a human
      monocytic cell line (THP-1). A p value <=0.05 was considered significant.
      RESULTS: MPs were absent in noninflamed foci in patients, whereas NDMPs were
      present in locations of inflammation. NDMPs were added to cultured THP-1 cells to
      quantify immunomodulatory effects. THP-1 cells were able to phagocytose NDMPs.
      Cells that ingested NDMPs demonstrated increased activation. In contrast,
      bystander THP-1 cells without ingested NDMPs demonstrated decreased activation.
      CONCLUSION: NDMPs are generated at the site of inflammation in patients with
      critical illness during sepsis. They have a divergent effect on the immune
      response by activating phagocytic cells and deactivating bystander cells. NDMPs
      may play an important role in regulating the inflammatory response to sepsis in
      patients with critical illness.

PMID- 22846947
TI  - 17beta-Estradiol attenuates cytokine-induced nitric oxide production in rat
      hepatocyte.
AB  - OBJECTIVE: Nitric oxide (NO) regulation during shock and sepsis is complex. NO
      production by endothelial NO synthase maintains microvascular perfusion and
      prevents shock-induced organ injury. However, the overproduction of NO by
      inducible NO synthase (iNOS) contributes to liver dysfunction after shock and is
      associated with increased tissue damage and mortality. Estrogen improves organ
      function and outcome after shock and sepsis, but the mechanism is unknown. We
      hypothesized that 17beta-estradiol would improve organ function by regulating the
      production of hepatocyte NO. METHODS: Isolated rat hepatocytes were stimulated in
      vitro with pro-inflammatory cytokines to induce NO synthesis with or without
      estrogen. Nitrite was detected after 24 hours. INOS protein was determined using
      Western blot analysis. RESULTS: Cytokine stimulation increased nitrite and iNOS
      protein in a dose-dependent manner. The cytokine-induced nitrite increase was
      significantly decreased by estrogen. iNOS expression was also diminished in
      cultures with the higher doses of estrogen. CONCLUSION: 17beta-Estradiol
      decreases cytokine-stimulated iNOS expression and NO production. The down
      regulation of iNOS expression may account for the beneficial role of estrogens in
      models of sepsis and shock.

PMID- 22846948
TI  - The utility of procalcitonin in critically ill trauma patients.
AB  - BACKGROUND: Procalcitonin (PCT), the prohormone of calcitonin, has an early and
      highly specific increase in response to systemic bacterial infection. The
      objectives of this study were to determine the natural history of PCT for
      patients with critical illness and trauma, the utility of PCT as a marker of
      sepsis versus systemic inflammatory response syndrome (SIRS), and the association
      of PCT level with mortality. METHODS: PCT assays were done on eligible patients
      with trauma admitted to the trauma intensive care unit (ICU) of a Level I trauma
      center from June 2009 to June 2010, at hours 0, 6, 12, 24, and daily until
      discharge from ICU or death. Patients were retrospectively diagnosed with SIRS or
      sepsis by researchers blinded to PCT results. RESULTS: A total of 856 PCT levels
      from 102 patients were analyzed, with mean age of 49 years, 63% male, 89% blunt
      trauma, mean Injury Severity Score of 21, and hospital mortality of 13%. PCT
      concentration for patients with sepsis, SIRS, and neither were evaluated. Mean
      PCT levels were higher for patients with sepsis versus SIRS (p < 0.0001).
      Patients with a PCT concentration of 5 ng/mL or higher had an increased mortality
      when compared with those with a PCT of less than 5 ng/mL in a univariate analysis
      (odds ratio, 3.65; 95% confidence interval, 1.03-12.9; p = 0.04). In a
      multivariate logistic analysis, PCT was found to be the only significant
      predictor for sepsis (odds ratio, 2.37; 95% confidence interval,1.23-4.61, p =
      0.01). CONCLUSION: PCT levels are significantly higher in ICU patients with
      trauma and sepsis and may help differentiate sepsis from SIRS in critical
      illness. An elevated PCT level was associated with increased mortality.

PMID- 22846949
TI  - Computational gene mapping to analyze continuous automated physiologic monitoring
      data in neuro-trauma intensive care.
AB  - BACKGROUND: We asked whether the advanced machine learning applications used in
      microarray gene profiling could assess critical thresholds in the massive
      databases generated by continuous electronic physiologic vital signs (VS)
      monitoring in the neuro-trauma intensive care unit. METHODS: We used Class
      Prediction Analysis to predict binary outcomes (life/death, good/bad Extended
      Glasgow Outcome Score, etc.) based on data accrued within 12, 24, 48, and 72
      hours after admission to the neuro-trauma intensive care unit. Univariate
      analyses selected "features," discriminator VS segments or "genes," in each
      individual's data set. Prediction models using these selected features were then
      constructed using six different statistical modeling techniques to predict
      outcome for other individuals in the sample cohort based on the selected features
      of each individual then cross-validated with a leave-one-out method. RESULTS: We
      gleaned complete sets of 588 VS monitoring segment features for each of four
      periods and outcomes from 52 of 60 patients with severe traumatic brain injury
      who met study inclusion criteria. Overall, intracranial pressures and blood
      pressures over time (e.g., intracranial pressure >20 mm Hg for 20 minutes)
      provided the best discrimination for outcomes. Modeling performed best in the
      first 12 hours of care and for mortality. The mean number of selected features
      included 76 predicting 14-day hospital stay in that period, 11 predicting
      mortality, and 4 predicting 3-month Extended Glasgow Outcome Score. Four of the
      six techniques constructed models that correctly identified mortality by 12 hours
      75% of the time or higher. CONCLUSION: Our results suggest that valid prediction
      models after severe traumatic brain injury can be constructed using gene mapping
      techniques to analyze large data sets from conventional electronic monitoring
      data, but that this methodology needs validation in larger data sets, and that
      additional unstructured learning techniques may also prove useful.

PMID- 22846950
TI  - Chemical venous thromboembolic prophylaxis is safe and effective for patients
      with traumatic brain injury when started 24 hours after the absence of hemorrhage
      progression on head CT.
AB  - BACKGROUND: Venous thromboembolism (VTE) continues to be an important
      complication for patients with trauma, including patients with intracranial
      hemorrhage. We implemented a protocol starting chemical prophylaxis 24 hours
      after the absence of progression of hemorrhage on computed tomography (CT) to
      increase consistency with the use of chemical venous thromboembolic prophylaxis
      in this population. The objective of this study was to review the protocol of VTE
      prophylaxis for patients with traumatic brain injury at our institution to
      determine whether it has been effective and safe in preventing VTE without
      increasing intracranial hemorrhage. METHODS: A retrospective case series was
      conducted to study 205 patients with intracranial hemorrhage admitted to a Level
      I trauma center during a 24-month period. These patients were reviewed with
      respect to type of intracranial injury, need for surgery, injury severity, time
      to initiation of chemical prophylaxis, and progression of injury on brain CT.
      Patients with a hospital length of stay less than 3 days or nonstable CT were
      excluded in the analysis of administration of chemical prophylaxis. Time to
      chemical prophylaxis in relation to absence of progression on brain CT was
      examined as well as the subsequent risk of progression of hemorrhage and risk of
      VTE events. The overall rate of venous thromboembolism was compared with that of
      matched historical controls. RESULTS: All patients received mechanical
      prophylaxis in the form of sequential compression devices. One hundred sixty-two
      intracranial hemorrhages were identified in 122 patients who met the study's
      inclusion criteria. Of this group of patients who did not have progression of
      hemorrhage on follow-up CT, 76.2% received chemical prophylaxis during their
      hospitalization.No patients had progression of intracranial hemorrhage after
      initiation of chemical VTE prophylaxis, and no patients developed VTE. This
      represents a decrease of VTE from previous years. No other complications related
      to chemical VTE prophylaxis were identified. CONCLUSION: A protocol based on an
      early use of chemical venous thromboembolic prophylaxis after the absence of
      progression of tramatic intracranial hemorrhage does not result in increased
      progression of intracranial hemorrhage and reduced the rate of venous
      thromboembolic events at our institution.

PMID- 22846951
TI  - Midlevel practitioners can safely place intracranial pressure monitors.
AB  - BACKGROUND: Neurosurgical coverage is a challenge for many trauma centers.
      Midlevel practitioners (MLPs) can extend coverage by sharing the workload. Our
      objective was to determine whether the complication rates for intracranial
      pressure (ICP) monitor placement were similar between neurosurgeons and MLPs.
      METHODS: After obtaining institutional review board approval, the trauma registry
      at a Level I trauma center was searched for all ICP monitors placed between June
      2005 and March 2010. Complications were classified as major or minor. The study
      was designed as a noninferiority trial with a 5% absolute difference in major
      complications defined as acceptable, a priori. Time to monitor placement was a
      secondary outcome and was analyzed by Wilcoxon rank sum and multiple linear
      regression. RESULTS: One hundred seven patients were identified. Fifteen patients
      were excluded (inserted by trauma surgeon or MLP under direct supervision,
      ventricular drain, or inserted at an outside facility). Of the remaining 92, 22
      were inserted by neurosurgeons and 70 by MLPs. There was one major complication
      (cerebrospinal fluid leak) in a monitor placed by an MLP. The difference in
      complication rates was significantly less than 5% (1.4% vs. 0%, p = 0.0128). The
      minor complication rate was higher for MLPs (5.7% vs. 0%, p = 0.80). Craniotomy
      and placement on third shift were associated with shorter times to monitor
      placement. Nine monitors were inserted at the time of craniotomy, eight of them
      by the neurosurgeon. CONCLUSION: ICP monitors can be safely placed by midlevel
      practitioners with major complication rates not different from those of
      neurosurgeons.

PMID- 22846952
TI  - High-risk geriatric protocol: improving mortality in the elderly.
AB  - BACKGROUND: Injured geriatric patients pose unique challenges to the trauma team
      because of their abnormal responses to shock and injury. We have developed the
      high-risk geriatric protocol (GP) that seeks to identify high-risk geriatric
      patients. We hypothesized that a high-risk GP would improve outcome in this
      select group of patients. METHODS: Patients from 2000 to 2010 were included.
      Patients 65 years or older who met high-risk GP based on comorbidities and/or
      physiologic parameters were compared with those patients who had not received GP
      before its implementation as well as other non-GP patients. This protocol
      includes a geriatric consultation, as well as a lactate levels, arterial blood
      gas levels, and echo test to assess for occult shock. Age, trauma activation,
      preexisting conditions, Injury Severity Score, Revised Trauma Score, and
      mortality were reviewed. Univariate and multivariate analyses were conducted to
      identify factors predictive of mortality. RESULTS: A total of 3,902 patients were
      evaluated. Patients receiving GP were less likely to die (odds ratio, 0.63 [0.39
      0.99], p = 0.046). For all patients, there was a dramatic increase in mortality
      for those patients older than 75 years. CONCLUSION: The GP, adjusted for other
      covariates, significantly reduced mortality in our patient population. Thus, this
      study confirms the overall effectiveness of our GP, which is hallmarked by prompt
      identification of those patients with occult shock and a multidisciplinary care
      of the aged population.

PMID- 22846953
TI  - Effect of local anesthetic on microorganisms in a murine model of surgical site
      infection.
AB  - BACKGROUND: Surgical site infections are common, with an incidence of 1.5% to 5%
      for all types of surgery. In vitro studies suggest an antimicrobial effect of
      local anesthetic. We hypothesized that subcutaneous infiltration of local
      anesthetic before surgical incision would reduce the incidence of postoperative
      wound infection. METHODS: In a wound infection model using 4- to 6-week-old
      female mice, Staphylococcus aureus and Escherichia coli were inoculated in
      surgical wounds infiltrated with local anesthetic or saline. On day 5, the mice
      were killed and tissues were evaluated for viable bacterial numbers, presence of
      bacteria histologically, and degree of inflammation on a scale of 0 to 3 based on
      number and types of inflammatory cells and presence of necrosis. RESULTS: A one
      way between-subjects analysis of variance with Tukey honestly significant
      difference post hoc comparisons showed no statistically significant difference in
      the degree of inflammation in mice infiltrated with lidocaine, lidocaine mixed
      with bupivacaine, or saline (p = 0.994, p = 0.337, and p = 0.792, respectively).
      A Tukey honestly significant difference post hoc analysis demonstrated that the
      saline (p = 0.038) and lidocaine mixed with bupivacaine (p = 0.006) had
      significantly lower degrees of inflammation than did the lidocaine group. A
      Bonferroni post hoc test demonstrated that those in the lidocaine (p = 0.003) and
      lidocaine mixed with bupivacaine (p = 0.008) groups had significantly higher
      inflammation than those in the saline group after controlling for the condition
      of the inocula. CONCLUSIONS: Infiltrate, whether saline, lidocaine, or lidocaine
      mixed with Marcaine, did not result in significantly different bacterial presence
      or higher degree of inflammation when controlling for experimental condition of
      bacterial inocula. Thus, subcutaneous infiltration of local anesthetic before a
      surgical incision is made does not reduce the incidence of bacterial growth or
      influence the degree of inflammation which alters infection rates.

PMID- 22846954
TI  - Does treatment of split-thickness skin grafts with negative-pressure wound
      therapy improve tissue markers of wound healing in a porcine experimental model?
AB  - BACKGROUND: Negative-pressure wound therapy (NPWT) has been used for to treat
      wounds for more than 15 years and, more recently, has been used to secure split
      thickness skin grafts. There are some data to support this use of NPWT, but the
      actual mechanism by which NPWT speeds healing or improves skin graft take is not
      entirely known. The purpose of this project was to assess whether NPWT improved
      angiogenesis, wound healing, or graft survival when compared with traditional
      bolster dressings securing split-thickness skin grafts in a porcine model.
      METHODS: We performed two split-thickness skin grafts on each of eight 30 kg
      Yorkshire pigs. We took graft biopsies on postoperative days 2, 4, 6, 8, and 10
      and submitted the samples for immunohistochemical staining, as well as standard
      hematoxylin and eosin staining. We measured the degree of vascular ingrowth via
      immunohistochemical staining for von Willenbrand's factor to better identify
      blood vessel epithelium. We determined the mean cross-sectional area of blood
      vessels present for each representative specimen, and then compared the bolster
      and NPWT samples. We also assessed each graft for incorporation and survival at
      postoperative day 10. RESULTS: Our analysis of the data revealed that there was
      no statistically significant difference in the degree of vascular ingrowth as
      measured by mean cross-sectional capillary area (p = 0.23). We did not note any
      difference in graft survival or apparent incorporation on a macroscopic level,
      although standard hematoxylin and eosin staining indicated that microscopically,
      there seemed to be better subjective graft incorporation in the NPWT samples and
      a nonsignificant trend toward improved graft survival in the NPWT group.
      CONCLUSION: We were unable to demonstrate a significant difference in vessel
      ingrowth when comparing NPWT and traditional bolster methods for split-thickness
      skin graft fixation. More studies are needed to elucidate the manner by which
      NPWT exerts its effects and the true clinical magnitude of these effects.

PMID- 22846955
TI  - "SCIP"ping antibiotic prophylaxis guidelines in trauma:  The consequences of
      noncompliance.
AB  - OBJECTIVE: The Surgical Care Improvement Project (SCIP) established surgical
      antibiotic prophylaxis guidelines as part of a national patient safety initiative
      aimed at reducing surgical complications such as surgical site infection (SSI).
      Although these antibiotic prophylaxis guidelines have become well established in
      surgical patients, they remain largely unstudied in patients with injury from
      trauma undergoing operative procedures. We sought to determine the role of these
      antibiotic prophylaxis guidelines in preventing SSI in patients undergoing trauma
      laparotomy. METHODS: A retrospective review of all patients who underwent
      emergency trauma laparotomy at two Level I trauma centers (2007-2008) revealed
      306 patients who survived more than 4 days after injury. Demographics and
      clinical risk SSI factors were analyzed, and patients were compared on the basis
      of adherence to the following SCIP guidelines: (1) prophylactic antibiotic given,
      (2) antibiotic received within 1 hour before incision, (3) correct antibiotic
      selection, and (4) discontinuation of antibiotic within 24 hours after surgery.
      The primary study end point was the development of SSI. RESULTS: The study sample
      varied by age (mean [SD], 32 [16] years) and injury mechanism (gunshot wound 44%,
      stab wound 27%, blunt trauma 30%). When patients with perioperative antibiotic
      management complying with the four SCIP antibiotic guidelines (n = 151) were
      compared with those who did not comply (n = 155), no difference between age,
      shock, small bowel or colon resection, damage control procedures, and skin
      closure was detected (p > 0.05). After controlling for injury severity score,
      hypotension, blood transfusion, enteric injury, operative duration, and other
      potential confounding variables in a multivariate analysis, complete adherence to
      these four SCIP antibiotic guidelines independently decreased the risk of SSI
      (odds ratio, 0.43; 95% confidence interval, 0.20-0.94; p = 0.035). Patients
      adhering to these guidelines less often developed SSI (17% vs. 33%, p = 0.001)
      and had shorter overall hospital duration of antibiotics (4 [6] vs. 9 [11] days,
      p < 0.001) and hospital length of stay (14 [13] vs. 19 [23] days, p = 0.016),
      although no difference in mortality was detected (p > 0.05). CONCLUSIONS: Our
      results suggest that SCIP antibiotic prophylaxis guidelines effectively reduce
      the risk of SSI in patients undergoing trauma laparotomy. Despite the emergent
      nature of operative procedures for trauma, efforts to adhere to these antibiotic
      guidelines should be maintained.

PMID- 22846956
TI  - Impact of a graduated driver's license law on crashes involving young drivers in
      New York State.
AB  - BACKGROUND: Motor vehicle crashes constitute the greatest risk of injury for
      young adults. Graduated driver licensing (GDL) laws have been used to reduce the
      number of injuries and deaths in the young driver population. The New York State
      GDL law increased supervision of young driver and limited both time-of-day driven
      and number of passengers. This review examines the impact of a GDL enacted in New
      York in September 2003. METHODS: A retrospective review of New York State
      administrative databases from 2001 to 2009 was performed. During this period, a
      state-wide GDL requirement was implemented. Database review included all reported
      crashes to the New York State Department of Motor Vehicles by cause and driver
      age as well as motor fuel tax receipts by the New York State Comptroller's
      Office. Motor fuel tax receipts and consumption information were used as a proxy
      for overall miles driven. RESULTS: Before 2003, drivers younger than 18 years
      were involved in 90 fatal crashes and 10,406 personal-injury (PI) crashes,
      constituting 4.49% and 3.38% of all fatal and PI crashes in New York State,
      respectively. By 2009, the number of fatal and PI crashes involving drivers who
      are younger than 18 years decreased to 44 (2.87%) and 5,246 (2.24%),
      respectively. Of note, the number of crashes experienced by the age group 18
      years to 20 years during this period also declined, from 192 (9.59% of all fatal
      crashes) and 25,407 (8.24% of all PI crashes) to 135 (8.81%) and 18,114 (7.73%),
      respectively. Overall numbers of crashes reported remained relatively stable,
      between 549,000 in 2001 and 520,000 in 2009. Motor fuel use during this period
      also declined, but to a lesser degree ($552 million to $516 million or 6.6%).
      CONCLUSION: The use of a GDL law in New York State has shown a large decrease in
      the number of fatalities and PI crashes involving young drivers. The delay in
      full driver privileges from the GDL did not result in an increase in fatal or PI
      crashes in the next older age group.

PMID- 22846957
TI  - Screening for traumatic stress among survivors of urban trauma.
AB  - OBJECTIVE: This study piloted the use of the Primary Care PTSD (PC-PTSD)
      screening tool in an outpatient setting to determine its utility for broader use
      and to gather data on traumatic stress symptoms among direct (patients) and
      indirect (families) survivors of traumatic injuries. METHODS: Using the PC-PTSD
      plus one question exploring openness to seeking help, participants were screened
      for PTSD in the outpatient clinic of an urban Level 1 trauma center. The survey
      was distributed during a 23-week period from April to September 2011. The screen
      was self-administered, a sample of convenience, and participation was voluntary
      and anonymous. RESULTS: With a response rate of 66%, 307 surveys were completed.
      Forty-two percent of participants had a positive screen. Patients greater than 30
      and 90 days from injury had 1.5 and 1.7 times more positive screens than those
      less than 30 days. Patients with gunshot wounds were 13 times as likely as those
      with falls and twice as likely as those in a motor vehicle crash to have a
      positive screen. Sixty percent of patients with a positive screen noted it would
      be helpful to talk to someone. CONCLUSION: The PC-PTSD was an easy to administer
      screening tool. Patients reported PTSD symptoms at higher rates than previous
      studies. Patients with gunshot wounds and those injured greater than 30 days from
      the time of the screen were more likely to report PTSD symptoms. Although males
      represented 82% of positive screens, there was no statistical difference in PTSD
      symptoms between male and female participants because of the small number of
      females represented. Families also reported significant levels of PTSD. Both
      patients and families may benefit from additional screening and intervention in
      the early posttrauma period.

PMID- 22846958
TI  - The dangers of being a "weekend warrior": a new call for injury prevention
      efforts.
AB  - BACKGROUND: Nonprofessionals routinely perform high-risk home maintenance
      activities otherwise regulated by the Occupational Health and Safety
      Administration when professionals perform the same work. Reducing the risks taken
      by these "weekend warriors" has not been the focus of injury prevention efforts.
      This study describes injury patterns and outcomes for nonprofessionals attempting
      home roof and tree maintenance. METHODS: We queried our trauma registry for all
      adult patients (age, >=18 years) with injury codes for "fall-from-height" or
      "struck-by-tree" (2005-present) and reviewed charts to determine injuries
      sustained during home roof or tree work. Patients injured during occupational
      duties (indicated by Workman's Compensation) were excluded. Descriptive
      statistics were used to determine patient demographics, injury patterns, and
      outcomes. RESULTS: A total of 129 patients were injured performing roof and tree
      maintenance during the study period. Of these patients, 90 (69.8%) were fall from
      height and 39 (30.2%) were struck by tree. Mean (SD) age was 45 (14) years. The
      majority were male (124, 96.1%) and white (116, 89.9%). Nearly half (59, 45.7%)
      were privately insured; a quarter (32, 24.8%) had no insurance. Mean (SD) Injury
      Severity Score was 12.7 (9.3). Injury distributions were as follows: head injury,
      48.8%; facial fractures, 10.1%; cervical spine fractures, 3.9%; thoracic, lumbar,
      and sacral spine fractures, 28.1%; rib fractures, 27.3%; intrathoracic injuries,
      22.5%; liver/spleen injuries, 6.2%; pelvic fractures, 15.6%; upper-extremity
      fractures, 27.3%; and lower-extremity fractures, 14.7%. Of the patients, 19
      (14.7%) had one or more regions with Abbreviated Injury Scale score of higher
      than 3. Mean (SD) length of stay was 5.3 (7.6) days. Except for 2 deaths (1.6%),
      discharge dispositions were as follows: home, 64.2%; home with services, 10.1%;
      rehabilitation, 17.8%; and skilled nursing, 5.4%. CONCLUSION: Weekend warriors
      performing home roof and tree maintenance sustain serious injuries with a
      potential for a long-term disability at young ages. Injury prevention efforts
      should educate the public about the hazards of high-risk home maintenance,
      possibly encouraging Occupational Health and Safety Administration-regulated
      protective measures or deferral to trained professionals.

PMID- 22846959
TI  - The influence of unit-based nurse practitioners on hospital outcomes and
      readmission rates for patients with trauma.
AB  - BACKGROUND: With the increased restrictions on resident work hours, hospitals
      increasingly are relying on advance practice nurses and physician assistants to
      help meet the patient care demand. We have created a workflow model wherein unit
      based nurse practitioners (UBNPs) provide the minute-to-minute care for patients
      with trauma in one specific unit in our hospital, with supervision by the
      attending surgeons. Patients with trauma may also be admitted to other units,
      where the care model is a traditional resident-run (RR) service, again with
      supervision by the attending staff. Our aim was to determine if there were
      differences between the care provided by UBNPs and residents. METHODS: We queried
      our trauma database for all patients admitted to our urban, academic, Level I
      trauma center from January 1, 2007, to August 31, 2010. Patients discharged alive
      from the trauma service were identified and cross-referenced with an
      administrative database to collect demographics, injury characteristics,
      comorbidities, complications, and discharge information. Patients cared for by
      the UBNPs were compared with those cared for by the RR service. chi2, Fisher's
      exact, and Student's t tests were used to determine significance. Significant
      factors were then tested with a multivariate linear regression analysis. p < 0.05
      was considered significant. RESULTS: During the study period, 3,859 patients were
      discharged alive from the trauma service, 2,759 (71.5%) from the UBNPs service,
      and 1,100 (28.5%) from the RR service. Demographic data and mean Injury Severity
      Score (11.6 vs. 11.1, p = 0.24) were similar for the two groups, although mean
      abdominal Abbreviated Injury Score was higher for the UBNP group (0.6 vs. 0.5, p
      = 0.02). UBNP patients were more likely to be diagnosed with deep venous
      thrombosis (4% vs. 2.5%, p = 0.02) and were more likely to be discharged to home
      (67% vs. 60%, p = 0.002). Mean (SD) length of stay for UBNP patients was 6.5
      (8.8) days compared with 7 (10.8) days for RR patients, although this difference
      did not reach statistical significance ( p = 0.17). The 30-day hospital
      readmission rates were similar for both groups (4.0% vs. 4.4%, p = 0.63).
      CONCLUSION: Care provided by UBNPs is equivalent to that provided by residents.
      With the restriction on resident work hours and greater reliance on nurse
      practitioners, patient care does not suffer. Moreover, a difference of 0.5 days
      in mean length of stay for the UBNP patients equates with more than 1,300 fewer
      patient care days. This difference, although not statistically significant, may
      be clinically relevant to physicians and administrators and may offset the cost
      of hiring UBNPs to help meet the patient care demand.

PMID- 22846960
TI  - Trauma fellowship.

PMID- 22846961
TI  - Union of forces.

PMID- 22846964
TI  - Sylvatic plague vaccine: a new tool for conservation of threatened and endangered
      species?
AB  - Plague, a disease caused by Yersinia pestis introduced into North America about
      100 years ago, is devastating to prairie dogs and the highly endangered black
      footed ferret. Current attempts to control plague in these species have
      historically relied on insecticidal dusting of prairie dog burrows to kill the
      fleas that spread the disease. Although successful in curtailing outbreaks in
      most instances, this method of plague control has significant limitations.
      Alternative approaches to plague management are being tested, including
      vaccination. Currently, all black-footed ferret kits released for reintroduction
      are vaccinated against plague with an injectable protein vaccine, and even wild
      born kits are captured and vaccinated at some locations. In addition, a novel,
      virally vectored, oral vaccine to prevent plague in wild prairie dogs has been
      developed and will soon be tested as an alternative, preemptive management tool.
      If demonstrated to be successful, oral vaccination of selected prairie dog
      populations could decrease the occurrence of plague epizootics in key locations,
      thereby reducing the source of bacteria while avoiding the indiscriminate
      environmental effects of dusting. Just as rabies in wild carnivores has largely
      been controlled through an active surveillance and oral vaccination program, we
      believe an integrated plague management strategy would be similarly enhanced with
      the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for
      prairie dogs. Control of plague in prairie dogs, and potentially other rodents,
      would significantly advance prairie dog conservation and black-footed ferret
      recovery.

PMID- 22846965
TI  - Astrocyte activation: a key step in rotenone induced cytotoxicity and DNA damage.
AB  - Astrocytes are the most abundant glial cells, which provide metabolic support for
      neurons. Rotenone is a botanical pesticide of natural origin, known to exhibit
      neurotoxic potential via inhibition of mitochondrial complex-I. This study was
      carried out to explore the effect of rotenone on C6 cells. The cell line C6
      derived from rat glioma cells represents astrocyte-like cell. C6 cells were
      treated with rotenone (0.1, 1 and 10 MUM) for 4 h. The effect of rotenone was
      studied on cell survival (MTT reduction and PI uptake); free radicals (ROS and
      RNS) and DNA damage (comet assay and Hoechst staining). The glial cell activation
      and apoptotic cell death was evaluated by expression of Glial fibrillary acidic
      protein (GFAP) and caspase-3 respectively. The treatment with rotenone resulted
      in decreased cell survival and increased free radical generation. Altered nuclear
      morphology and DNA damage were evident following rotenone treatment in Hoechst
      staining and Comet assay. Rotenone elevated expression of GFAP and caspase-3 that
      indicates glial cell activation and apoptosis, respectively. We further studied
      the effect of melatonin, an antioxidant, on the observed toxic effects. Co
      incubation of antioxidant, melatonin (300 MUM), significantly suppressed rotenone
      induced above-mentioned effects in C6 cells. Inhibitory effects of melatonin
      suggest that free radicals play a major role in rotenone induced astrocyte
      activation and cellular toxicity leading to apoptosis of astroglial cells.

PMID- 22846966
TI  - Pharmacokinetics of glutamate-oxaloacetate transaminase and glutamate-pyruvate
      transaminase and their blood glutamate-lowering activity in naive rats.
AB  - Traumatic brain injury (TBI) and stroke lead to elevated levels of glutamate in
      the brain that negatively affect the neurological outcomes in both animals and
      humans. Intravenous administration of glutamate-oxaloacetate transaminase (GOT)
      and glutamate-pyruvate transaminase (GPT) enzymes can be used to lower the blood
      glutamate levels and to improve the neurological outcome following TBI and
      stroke. The objective of this study was to analyze the pharmacokinetics and to
      determine the glutamate-lowering effects of GOT and GPT enzymes in naive rats. We
      determined the time course of serum GOT, GPT, and glutamate levels following a
      single intravenous administration of two different doses of each one of the
      studied enzymes. Forty-six male rats were randomly assigned into one of 5
      treatment groups: saline (control), human GOT at dose 0.03 and 0.06 mg/kg and
      porcine GPT at dose 0.6 and 1.2 mg/kg. Blood samples were collected at baseline,
      5 min, and 2, 4, 8, 12, and 24 h after the drug injection and GOT, GPT and
      glutamate levels were determined. The pharmacokinetics of both GOT and GPT
      followed one-compartment model, and both enzymes exhibited substantial glutamate
      lowering effects following intravenous administration. Analysis of the
      pharmacokinetic data indicated that both enzymes were distributed predominantly
      in the blood (central circulation) and did not permeate to the peripheral organs
      and tissues. Several-hour delay was present between the time course of the enzyme
      levels and the glutamate-lowering effects (leading to clock-wise hysteresis on
      concentration-effect curves), apparently due to the time that is required to
      affect the pool of serum glutamate. We conclude that the interaction between the
      systemically-administered enzymes (GOT and GPT) and the glutamate takes place in
      the central circulation. Thus, glutamate-lowering effects of GOT and GPT
      apparently lead to redistribution of the excess glutamate from the brain's
      extracellular fluid into the blood and can reduce secondary brain injury due to
      glutamate neurotoxicity. The outcomes of this study regarding the pharmacokinetic
      and pharmacodynamic properties of the GOT and GPT enzymes will be subsequently
      verified in clinical studies that can lead to design of effective neuroprotective
      treatment strategies in patients with traumatic brain diseases and stroke.

PMID- 22846967
TI  - Metabolic pathways and activity-dependent modulation of glutamate concentration
      in the human brain.
AB  - Glutamate is one of the most versatile molecules present in the human brain,
      involved in protein synthesis, energy production, ammonia detoxification, and
      transport of reducing equivalents. Aside from these critical metabolic roles,
      glutamate plays a major part in brain function, being not only the most abundant
      excitatory neurotransmitter, but also the precursor for gamma-aminobutyric acid,
      the predominant inhibitory neurotransmitter. Regulation of glutamate levels is
      pivotal for normal brain function, as abnormal extracellular concentration of
      glutamate can lead to impaired neurotransmission, neurodegeneration and even
      neuronal death. Understanding how the neuron-astrocyte functional and metabolic
      interactions modulate glutamate concentration during different activation status
      and under physiological and pathological conditions is a challenging task, and
      can only be tentatively estimated from current literature. In this paper, we
      focus on describing the various metabolic pathways which potentially affect
      glutamate concentration in the brain, and emphasize which ones are likely to
      produce the variations in glutamate concentration observed during enhanced
      neuronal activity in human studies.

PMID- 22846970
TI  - Stereotactic body radiotherapy: do central lung tumors still represent a 'no-fly
      zone'?.

PMID- 22846968
TI  - Role of oxidative stress and Ca2+ signaling on molecular pathways of neuropathic
      pain in diabetes: focus on TRP channels.
AB  - Diabetes mellitus, a debilitating chronic disease, affects ~100 million people.
      Peripheral neuropathy is one of the most common early complications of diabetes
      in ~66 % of these patients. Altered Ca(2+) handling and Ca(2+) signaling were
      detected in a huge variety of preparations isolated from animals with
      experimentally induced type 1 and 2 diabetes as well as patients suffering from
      the disease. We reviewed the role of Ca(2+) signaling through cation channels and
      oxidative stress on diabetic neuropathic pain in sensory neurons. The
      pathogenesis of diabetic neuropathy involves the polyol pathway, advanced
      glycation end products, oxidative stress, protein kinase C activation,
      neurotrophism, and hypoxia. Experimental studies with respect to oxidative stress
      and Ca(2+) signaling, inhibitor roles of antioxidants in diabetic neuropathic
      pain are also summarized in the review. We hypothesize that deficits in insulin,
      triggers alterations of sensory neurone phenotype that are critical for the
      development of abnormal Ca(2+) homeostasis and oxidative stress and associated
      mitochondrial dysfunction. The transient receptor potential channels are a large
      family of proteins with six main subfamilies. The sheer number of different TRPs
      with distinct functions supports the statement that these channels are involved
      in a wide range of processes ranging in diabetic neuropathic pain and it seems
      that the TRPC, TRPM and TRPV groups are mostly responsible from diabetic
      neuropathic pain. In conclusion, the accumulating evidence implicating Ca(2+)
      dysregulation and over production of oxidative stress products in diabetic
      neuropathic pains, along with recent advances in understanding of genetic
      variations in cation channels such as TRP channels, makes modulation of neuronal
      Ca(2+) handling an increasingly viable approach for therapeutic interventions
      against the painful and degenerative aspects of many diabetic neuropathies.

PMID- 22846969
TI  - Protective effect of diphenyl diselenide on ischemia and reperfusion-induced
      cerebral injury: involvement of oxidative stress and pro-inflammatory cytokines.
AB  - Cerebrovascular diseases, including ischemic stroke, are associated with high
      mortality worldwide. Oxidative stress and inflammation are important
      pathophysiological mechanisms involved in post-ischemic cerebral injury. The
      present study was designed to investigate the potential protective effect of
      diphenyl diselenide (PhSe)(2), an organoselenium compound with antioxidant and
      anti-inflammatory properties, against ischemia/reperfusion (I/R) insult in rat
      brain. The experimental model adopted was that of surgically-induced brain
      ischemia, performed by means of bilateral common carotid artery occlusion in
      rats. The effect of a single oral dose of (PhSe)(2) (50 mg/kg), administered 30
      min before the onset of ischemia, was investigated by assessing cerebral
      oxidative stress-related biochemical parameters and pro-inflammatory cytokines in
      plasma of rats. The results demonstrated an increase in the levels of
      malondialdehyde (MDA), reactive oxygen species (ROS) and nitrate/nitrite as well
      as the alteration in the non-enzymatic and enzymatic (catalase and superoxide
      dismutase) antioxidant defense system induced by I/R insult in rat brain. I/R
      insult increased the levels of IL-1beta, IL-6, TNF-alpha and INF-gamma in plasma
      of rats. The administration of (PhSe)(2) restored cerebral levels of MDA, ROS,
      nitrate/nitrite and antioxidant defenses of rats exposed to I/R insult. (PhSe)(2)
      markedly reduced pro-inflammatory cytokines in plasma of I/R rats. I/R insult
      increased the plasma levels of tissue damage markers, such as creatine kinase and
      alpha-1-acid glycoprotein. Pretreatment with (PhSe)(2) was effective in reducing
      the levels of these proteins. In addition, (PhSe)(2) attenuated cerebral
      histological alterations induced by I/R. This study showed for the first time the
      in vivo protective effect of (PhSe)(2) against oxidative stress and pro
      inflammatory cytokines-induced by I/R insult in rats.

PMID- 22846971
TI  - Image-guided hypofractionated small volume radiotherapy of non-small cell lung
      cancer - feasibility and clinical outcome.
AB  - PURPOSE: Local hypofractionated stereotactic radiation treatment (hfSRT) of early
      stage non-small cell lung cancer (NSCLC) represents a highly effective treatment
      alternative in medically inoperable patients. METHOD: Between June 2007 and
      December 2010, 65 patients with NSCLC were treated with image-guided
      hypofractionated radiotherapy. The Union Internationale Contre le Cancer (UICC)
      stage distribution was: IA, n = 19; IB, n = 15; IIB, n = 5; IIIA, n = 10; IIIB, n
      = 6; and IV, n = 10. The fractionation schedule used was 3 * 12.5 Gy (n = 36)
      prescribed to the encompassing 67% isodose line for peripheral primary tumours,
      and 8 * 6 Gy (n = 26) or 8 * 5 Gy (n = 3) prescribed to the encompassing 80%
      isodose line for centrally located tumours. RESULTS: Mean follow-up was 13.8
      months (range 1-41 months). Until now 6 patients developed a local recurrence, 2
      of them in combination with mediastinal lymph node failure. The 1-year actuarial
      local control rate was 93% and overall survival 79%. Pneumonitis was seen in 14
      patients (21.5%) (Common Terminology Criteria for Adverse Events (CTCAE) grade I:
      n = 12, and II: n = 2) after a median time period of 9.5 months. No patient
      developed pneumonitis of CTCAE grade III or higher. CONCLUSION: Image-guided
      hfSRT is effective and feasible in patients with non-operable NSCLC, even in
      higher stages, whenever local control is crucial and there are contraindications
      against systemic therapy.

PMID- 22846972
TI  - Reduced E-cadherin expression is a predictor of lower overall survival and
      metastatic disease in invasive ductal breast cancer.
AB  - BACKGROUND: E-cadherin, a transmembrane adhesion molecule, is implicated in the
      development of many solid tumors as well as in the acquisition of metastatic
      potential of epithelial tumors. Its clinical use has yet to be established.
      PATIENTS AND METHODS: The prognostic value of E-cadherin expression in 134
      invasive ductal breast carcinoma patients over a 10-year follow-up period was
      investigated. Additionally, the correlation between E-cadherin expression and
      other traditional prognostic factors was investigated. RESULTS: A statistically
      significant influence on overall survival was found for estrogen receptor, tumor
      size, histological and nuclear grade, HER2, lymph node involvement, vascular
      invasion, proliferative index, and E-cadherin. E-cadherin expression had a
      significant impact on overall survival and development of metastases in the group
      of patients not receiving chemotherapy, while it had no such effect in the group
      of patients who received chemotherapy. CONCLUSION: We conclude that determination
      of E-cadherin expression can be used as an adjunct in selecting patients who may
      benefit from adjuvant chemotherapy in the presence of otherwise favorable
      prognostic factors.

PMID- 22846973
TI  - Comparison of the effects of two kinase inhibitors, sorafenib and dasatinib, on
      chronic lymphocytic leukemia cells.
AB  - BACKGROUND: With sorafenib displaying the highest affinities for Flt3, VEGFR
      (vascular endothelial growth factor receptor) and Raf and dasatinib for Abl and
      Src kinases, the profiles of kinases targeted by these inhibitors differ
      strongly. MATERIALS AND METHODS: Dose-dependent effects of the inhibitors on
      freshly isolated chronic lymphocytic leukemia (CLL) cells were assessed as
      increased phosphatidylserine exposure. Inhibition by sorafenib and dasatinib of
      survival and anti-apoptotic signaling in CLL cells was examined by Western blot
      analysis. RESULTS: Sorafenib uniformly induced apoptosis in CLL lymphocytes with
      a concentration inhibiting by 50% (IC50) of 8 mM, whereas the response to
      dasatinib was heterogeneous with the onset of inhibition at submicromolar
      concentrations but with IC50 values below 25 mM in only a few samples. At the
      respective pharmacologically achievable plasma concentrations, the inhibitors
      showed more efficient apoptosis induction by sorafenib than by dasatinib and less
      than additive mutual enhancement in combination. Co-culture with the bone marrow
      stroma cell line HS-5 increased the viability of untreated CLL cells but did not
      protect from sorafenib-induced apoptosis. CONCLUSIONS: Sorafenib or dasatinib
      displayed sigmoidal or saturation-type dose-response relationships for apoptosis
      induction, which were uniform or highly divergent, respectively, among individual
      CLL samples and therefore might complement each other in their clinical potential
      for CLL.

PMID- 22846974
TI  - Prospective phase II study of neoadjuvant therapy with cisplatin, 5-fluorouracil,
      and bevacizumab for locally advanced resectable esophageal cancer.
AB  - BACKGROUND: We investigated the efficacy and tolerability of cisplatin and 5
      fluorouracil (5-FU) plus bevacizumab as neoadjuvant therapy for patients with
      locally advanced resectable esophageal cancer. PATIENTS AND METHODS: In this
      prospective phase II study, 22 patients with adenocarcinoma and 6 with squamous
      cell carcinoma received 2 4-day cycles of bevacizumab 7.5 mg/kg followed by
      cisplatin 80 mg/m(2) infusion on day 1 followed by 5-FU 1,000 mg/m(2) as a 96-h
      continuous infusion on days 1-4, separated by a 3-week interval. RESULTS: The
      response rate was 39%, the R0 resection rate was 43%, and the median overall
      survival (OS) was 17 months. The regimen was well tolerated, with the most common
      severe toxicities being venous thromboembolism (10%), nausea, and
      gastrointestinal bleeding (7% each). In 37 patients previously treated with
      cisplatin and 5-FU alone at our institution and thus serving as historical
      controls, the response rate was 30%, the R0 resection rate was 44%, and the
      median OS was 23 months. There was no statistically significant difference
      between the 2 groups of patients. CONCLUSION: Adding bevacizumab to cisplatin and
      5-FU neoadjuvant chemotherapy was active and well tolerated but did not seem to
      improve the resection rate or OS compared with prior regimens, including the
      historical controls at our institution.

PMID- 22846975
TI  - The role of integrated 18F-FDG PET-CT as a staging tool for limited-stage small
      cell lung cancer: a retrospective study.
AB  - BACKGROUND: The aim of this study was to evaluate whether positron emission
      tomography-computed tomography (PET-CT) could be used as part of the staging work
      up in patients with limited-stage disease (LD) small cell lung cancer (SCLC).
      PATIENTS AND METHODS: Between January 2002 and December 2007, a total of 73
      patients with presumed LD on CT, who underwent a PET-CT scan, were included in
      this study. RESULTS: Conventional work-up revealed distant metastases in 12
      patients. Out of 61 patients diagnosed as LD SCLC, PET-CT found unexpected
      distant metastases in 15 (24.6%) patients (LD/extensive-stage disease (ED)) of
      whom 13 (21.3%) were upstaged as a consequence. In 10 (76.9%) of the 13 upstaged
      patients, treatment was changed. The median survival of LD/LD SCLC patients who
      underwent concurrent chemoradiotherapy and chemotherapy only was 21.9 and 17.5
      months, respectively. The median survival of LD/ED and ED/ED SCLC patients who
      received chemotherapy only was 17.4 and 14.1 months, respectively. The median
      survival of LD/LD SCLC patients who received concurrent chemoradiotherapy was
      superior to that of LD/ ED and ED/ED patients who received chemotherapy only (p =
      0.037 and 0.004, respectively). CONCLUSION: The addition of PET-CT seems to allow
      more accurate staging and may thus protect a percentage of SCLC patients from
      potentially futile and toxic radiotherapy.

PMID- 22846976
TI  - Administration of chemotherapy by an arteriovenous fistula in a patient with
      metastatic rectal cancer after life-threatening, port thrombosis-associated cava
      superior syndrome. An option for patients without possibility of peripheral or
      central venous access.
AB  - BACKGROUND: Patients with solid tumors have an increased risk of venous
      thromboembolism, potentially related to a venous port system. In case of catheter
      related thrombosis despite full anticoagulation, further treatment administration
      is difficult. CASE REPORT: A 41-year-old female patient with a K-Ras wild-type
      adenocarcinoma of the rectum was diagnosed with systemic disease in June 2008
      after several local recurrences treated with surgery and additive chemotherapy.
      To administer chemotherapy with FOLFIRI (folinic acid, 5-fluorouracil,
      irinotecan) and bevacizumab, a venous port system into the vena subclavia was
      implanted. In April 2009, the computed tomography (CT) scan revealed a
      portassociated thrombosis with cava superior syndrome, despite treatment with
      phenprocoumon and an international normalized ratio (INR) of 3.75 at the time of
      the event. The port system was explanted. According to the possible relationship
      to bevacizumab, treatment was discontinued, followed by rapid disease
      progression. Access to peripheral veins became virtually impossible. Therefore, a
      radiocephalic fistula was established. For 9 months, the patient has been
      receiving several therapeutic agents with 20 punctures of the fistula, revealing
      no locoregional events (e.g. arterial, venous or cutaneous). CONCLUSION: The
      application of current therapeutic agents by an arteriovenous fistula seems to be
      a feasible option for patients with restricted peripheral or central vein status
      and/or medical history of thrombotic events disabling the use of a port system.

PMID- 22846977
TI  - Antiangiogenic treatment for multiple CNS hemangioblastomas.
AB  - BACKGROUND: Hemangioblastomas represent rare benign tumors of the central nervous
      system. In the case of metastatic spread and limited surgical options, systemic
      treatment may be considered. However there is no standard of care beyond surgery.
      CASE REPORT: We report the cases of 2 patients with progressive multilocular
      hemangioblastomas, who showed clinical benefit and radiological stabilization of
      tumor growth after treatment with bevacizumab, an antibody against the vascular
      endothelial growth factor. CONCLUSION: Our case reports suggest activity of
      bevacizumab in hemangioblastomas after failure of standard therapeutic options.

PMID- 22846978
TI  - Histiocytic sarcoma - targeted therapy: novel therapeutic options? A series of 4
      cases.
AB  - BACKGROUND: Histiocytic sarcoma (HS) is a rare but highly aggressive disease. The
      cancer-specific survival of patients with HS is short and only limited response
      to conventional chemotherapy or radiation therapy is seen. Some data from single
      case reports have suggested efficacy for high-dose chemotherapy and
      autologous/allogeneic stem cell transplantation. CASE REPORT: We report on 4
      cases of HS, and demonstrate that different druggable receptors are expressed on
      HS. Using immunohistochemistry, we detected the expression of platelet-derived
      growth factor receptor, vascular endothelial growth factor receptor and epidermal
      growth factor receptor, which are all well-known targets for novel targeted
      agents. Based on the marker profile, different novel targeted therapies including
      imatinib, sorafenib and bevacizumab were applied to the patients. We observed a
      varying clinical course for each patient. CONCLUSION: In our case series, we
      demonstrated that different receptors, which represent potential targets for
      novel drugs, are expressed on HS tumor cells. For a definitive assessment of the
      efficacy of these agents a prospective case study of a larger number of patients
      should be performed.

PMID- 22846979
TI  - Complete response in a patient with granulosa cell tumor treated with a
      combination of leuprolide and tamoxifen.
AB  - BACKGROUND: Adult granulosa cell tumors (GCTs) are frequently hormonally active.
      Thus, hormonal agents have been evaluated for the treatment of advanced-stage or
      recurrent disease. CASE REPORT: A 39-year-old patient presented with recurrent
      GCT. The patient received multiple treatment modalities, including surgery and 2
      different chemotherapy regimens (cisplatin- and taxanebased). Abdominal computed
      tomography following these treatments showed local recurrence with multiple
      implants. The patient's inhibin B level increased to 187 pg/ml at this time. The
      patient was treated with leuprolide 11.25 mg every 3 months and tamoxifen 20 mg
      twice daily. The patient's inhibin B level began to decrease after 1 month and
      returned to normal after 4 months. The patient has been maintained on this
      treatment for 2 years and has tolerated the drugs well. CONCLUSION: The
      combination of leuprolide and tamoxifen had limited side effects in the presented
      patient and might be a viable treatment option for women with advanced-stage or
      recurrent adult ovarian GCTs.

PMID- 22846980
TI  - Sunitinib in patients with cisplatin-refractory germ cell tumors.

PMID- 22846981
TI  - Tripeptide feG prevents and ameliorates acute pancreatitis-associated acute lung
      injury in a rodent model.
AB  - BACKGROUND: The synthetic tripeptide feG (D-Phe-D-Glu-Gly) is a novel
      pharmacologic agent that decreases neutrophil recruitment, infiltration, and
      activation in various animal models of inflammatory disease. We aimed to
      investigate the effect of feG as both a preventive treatment when administered
      before acute lung injury and as a therapeutic treatment administered following
      initiation of acute lung injury. METHODS: Lung injury was assessed following
      prophylactic or therapeutic intratracheal feG administration in a "two-hit"
      rodent model of acute pancreatitis plus intratracheal lipopolysaccharide.
      RESULTS: Following both prophylactic and therapeutic feG administration, there
      were significant improvements in arterial blood oxygenation and respiratory
      mechanics and decreased lung edema, BAL protein concentration, histologic tissue
      injury scores, BAL cell infiltration, and lung myeloperoxidase activity. Most
      indices of lung damage were reduced to baseline control values. CONCLUSIONS: feG
      reduced leukocyte infiltration, ameliorated the severity of inflammatory damage,
      and restored lung function when administered either prophylactically or
      therapeutically in a two-hit rat model of acute pancreatitis plus intratracheal
      lipopolysaccharide.

PMID- 22846982
TI  - Sleep, slow-wave sleep, and blood pressure.
AB  - There is increasing evidence that alterations in sleep continuity due to central
      nervous system arousal and/or reductions in deeper stages of sleep adversely
      affect blood pressure and contribute to hypertension. Disturbed sleep also blunts
      the normal nocturnal dip in blood pressure and may lead to sustained daytime
      hypertension as well. Nocturnal drops in blood pressure result from increased
      parasympathetic and reduced sympathetic activity during sleep. Slow-wave sleep,
      considered to be the most "restorative," is the specific sleep state associated
      with the largest decline in sympathetic activity. The time in slow-wave sleep
      declines with age as well as in association with other health problems. A
      reduction in the time in slow-wave sleep has recently been reported to predict
      increased incident hypertension. The mechanisms by which this occurs have not
      been well described but may include alterations in dipping patterns, sympathetic
      nervous system activity, corticotrophin pathways, and the renin-angiotensin
      system. This article reviews the overall association between sleep and
      hypertension, with a specific focus on slow-wave sleep, a possible novel target
      for future blood pressure interventions.

PMID- 22846983
TI  - Targeting hypertension in patients with cardiorenal metabolic syndrome.
AB  - Diabetes mellitus coexisting with hypertension is greater than chance alone would
      predict. Hypertensive patients have been shown to have altered composition of
      skeletal muscle tissue, decreased blood flow to skeletal muscle and post-receptor
      signaling alterations in the IRS insulin pathway, all inducing insulin resistance
      states, which partially explains why blood pressure goals in DM patients are
      lower than in normoglycemic patients. Although optimal first-step
      antihypertensive drug therapy in type 2 DM or impaired fasting glucose levels
      (IFG) should be individualized for each patient, converting enzyme inhibitors
      (ACEIs) or angiotensin receptor blockers (ARBs) have been demonstrated in some
      but not all studies to decrease the rate of development of proteinuria and
      diabetic renal disease. According to the ACCF/AHA 2011 Expert Consensus, elderly
      persons with diabetes, hypertension, and nephropathy should be initially treated
      with ACEIs or ARBs, although the choice of a specific antihypertensive may also
      depend on other associated comorbidities.

PMID- 22846985
TI  - In vivo bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation
      shells assembled on an alginate microbead core template.
AB  - Electrostatic interactions between polycations and polyanions are being explored
      to fabricate polyelectrolyte complexes (PEC) that could entrap and regulate the
      release of a wide range of biomolecules. Here, we report the in vivo application
      of PEC shells fabricated from three different polycations: poly-l-ornithine
      (PLO), poly-l-arginine (PLA) and DEAE-dextran (DEAE-D) to condense heparin on the
      surface of alginate microbeads and further control the delivery of recombinant
      human bone morphogenetic protein 2 (rhBMP-2) in spinal fusion application. We
      observed large differences in the behavior of PEC shells fabricated from the
      cationic polyamino acids (PLO and PLA) when compared to the cationic
      polysaccharide, DEAE-D. Whereas DEAE-D-based PEC shells eroded and released rhBMP
      2 over 2 days in vitro, PLO- and PLA-based shells retained at least 60% of loaded
      rhBMP-2 after 3 weeks of incubation in phosphate-buffered saline. In vivo
      implantation in a rat model of posterolateral spinal fusion revealed robust bone
      formation in the PLO- and PLA-based PEC shell groups. This resulted in a
      significantly enhanced mechanical stability of the fused segments. However, bone
      induction and biomechanical stability of spine segments implanted with DEAE-D
      based carriers were significantly inferior to both PLO- and PLA-based PEC shell
      groups (p<0.01). From these results, we conclude that PEC shells incorporating
      native heparin could be used for growth factor delivery in functional bone tissue
      engineering application and that PLA- and PLO-based complexes could represent
      superior options to DEAE-D for loading and in vivo delivery of bioactive BMP-2 in
      this approach.

PMID- 22846986
TI  - Effects of branched or linear architecture of bioreducible poly(amido amine)s on
      their in vitro gene delivery properties.
AB  - In this study, the gene delivery properties of new hyperbranched poly(amido
      amine)s (PAAs) with disulfide linkages in the main chain were investigated in
      comparison with their linear analogs. Eight different bioreducible PAAs were
      prepared by Michael addition of N,N'-bisacryloylpiperazine (BP) with cystamine
      (CYST) or N,N'-dimethylcystamine (DMC) and of N,N'-cystaminebisacrylamide (CBA)
      with N,N'-ethylenediamine (EDA) or N,N'-dimethylethylenediamine (DMEDA). In order
      to study the effect of terminal groups on the transfection efficiency, each
      polymer was terminated with 4-aminobutanol (ABOL) or with 2-aminoethanol (ETA).
      The hyperbranched and the linear PAAs generally formed polyplexes with plasmid
      DNA with sizes around 200nm and positive zeta potentials ranging from +10 to
      +22mV at polymer/DNA weight ratios equal or higher than 3/1. Remarkably low or no
      cytotoxicity was observed for both hyperbranched and linear PAAs. Hyperbranched
      CBA-containing PAAs showed higher gene expression in DNA transfection tests with
      COS-7 cells than their linear analogs and up to two times higher than linear PEI
      that was used as the reference polymer. Transfection efficiencies of the branched
      PAAs were generally enhanced by the presence of serum, which is a promising
      property for future in vivo studies with these hyperbranched PAAs. In this study
      the ease of synthetic modification of both linear and hyperbranched poly(amido
      amide)s and the versatility of hyperbranched PAAs in regulating DNA transfection
      and cytotoxicity are demonstrated. The results show the large possibilities for
      this class of polymers to provide polymeric vectors with controllable properties
      for gene therapy applications.

PMID- 22846984
TI  - The Dietary Approaches to Stop Hypertension (DASH) eating pattern in special
      populations.
AB  - The Dietary Approaches to Stop Hypertension (DASH) trial showed that a diet rich
      in fruits, vegetables, low-fat dairy products with reduced total and saturated
      fat, cholesterol, and sugar-sweetened products effectively lowers blood pressure
      in individuals with prehypertension and stage I hypertension. Limited evidence is
      available on the safety and efficacy of the DASH eating pattern in special
      patient populations that were excluded from the trial. Caution should be
      exercised before initiating the DASH diet in patients with chronic kidney
      disease, chronic liver disease, and those who are prescribed renin-angiotensin
      aldosterone system antagonist, but these conditions are not strict
      contraindications to DASH. Modifications to the DASH diet may be necessary to
      facilitate its use in patients with chronic heart failure, uncontrolled diabetes
      mellitus type II, lactose intolerance, and celiac disease. In general, the DASH
      diet can be adopted by most patient populations and initiated simultaneously with
      medication therapy and other lifestyle interventions.

PMID- 22846988
TI  - Effect of the stability and deformability of self-assembled glycol chitosan
      nanoparticles on tumor-targeting efficiency.
AB  - To evaluate the tumor targeting efficiency of self-assembled polymeric
      nanoparticles, four glycol chitosan nanoparticles (CNPs) with different degrees
      of hydrophobic substitution were prepared by coupling 7.5, 12, 23, and 35 wt.% of
      5beta-cholanic acid to hydrophilic glycol chitosan polymer (GC). The sizes and
      zeta-potentials of different CNPs in aqueous condition were not significantly
      different, but their stability and deformability were greatly dependent upon the
      degree of substitution (DS) of 5beta-cholanic acid. With an increase in
      hydrophobicity, CNPs became more stable and rigid, as characterized by SDS-PAGE
      and filtration tests. To compare with CNPs, linear GC and polystyrene
      nanoparticles (PSNPs) were employed as controls. In vivo tumor accumulation of
      Cy5.5-labeled linear GC, polystyrene nanoparticles (PSNPs) and CNPs were
      monitored in flank tumors and liver tumor-bearing mice models using near-infrared
      fluorescence (NIRF) imaging systems. CNPs displayed higher tumor accumulation
      than GC and PSNPs via the enhanced permeability and retention (EPR) effect.
      Interestingly, CNPs containing 23 wt.% of 5beta-cholanic acid (CNP-23%) showed
      the highest tumor-targeting efficiency compared to other CNPs. As exemplified in
      this study, the stability of CNP-23% is better than CNP-7.5% and CNP-12%
      containing 7.5 wt.% and 12 wt.% of 5beta-cholanic acid, respectively, and the
      deformability of CNP-23% is better than that of CNP-35% containing 35 wt.% of
      5beta-cholanic acid. We proposed that the superior tumor-targeting efficiency of
      CNP-23% is mainly due to their balanced stability and deformability in vivo. This
      study demonstrates that the degree of hydrophobic substitution of self-assembled
      nanoparticles could determine their stability and deformability. Importantly,
      they were founded to be the key factors which affect their tumor-targeting
      efficiency in vivo, and so that these factors should be highly considered during
      developing nanoparticles for tumor-targeted imaging or drug delivery.

PMID- 22846987
TI  - Conjunctival vaccination against Brucella ovis in mice with mannosylated
      nanoparticles.
AB  - The use of sub-unit vaccines can solve some drawbacks associated with traditional
      attenuated or inactivated ones. However, in order to improve their
      immunogenicity, these vaccines needs to be associated to an appropriate adjuvant
      which, adequately selected, may also offer an alternative pathway for
      administration. The aim of this work was to evaluate the protection offered by
      the hot saline complex extracted from Brucella ovis (HS) encapsulated in
      mannosylated nanoparticles (MAN-NP-HS) when instilled conjunctivally in mice.
      Nanoparticles displayed a size of 300 nm and the antigen loading was close to 30
      MUg per mg nanoparticle. Importantly, encapsulated HS maintained its protein
      profile, structural integrity and antigenicity during and after the preparative
      process of nanoparticles. The ocular immunization was performed on BALB/c mice.
      Eight weeks after vaccination animals were challenged with B. ovis, and 3 weeks
      later, were slaughtered for bacteriological examinations. Animals immunized with
      MAN-NP-HS displayed a 3-log reduction in spleen CFU compared with unvaccinated
      animals. This degree of protection was significantly higher than that observed
      for the commercial vaccine (Rev1) subcutaneously administered. Interestingly, the
      mucosal IgA response induced by MAN-NP-HS was found to be much more intense than
      that offered by Rev1 and prolonged in time. Furthermore, the elicited IL-2, IL-4
      and gamma-IFN levels showed good correlation with the degree of protection. On
      the other hand, biodistribution studies in animals were performed with
      nanoparticles labelled with either (99m)technetium or rhodamine B isothiocyanate.
      The biodistribution revealed that, after instillation, MAN-NP-HS moved from the
      palpebral area to the nasal region and, the gastrointestinal tract. This profile
      of distribution was different to that observed for free (99m)TcO4- colloids,
      which remained for at least 24h in the site of administration. In summary,
      mannosylated nanoparticles appear to be a safe and suitable adjuvant for
      conjunctival vaccination.

PMID- 22846989
TI  - Reconstitution of the very short patch repair pathway from Escherichia coli.
AB  - The Escherichia coli very short patch (VSP) repair pathway corrects thymidine
      guanine mismatches that result from spontaneous hydrolytic deamination damage of
      5-methyl cytosine. The VSP repair pathway requires the Vsr endonuclease, DNA
      polymerase I, a DNA ligase, MutS, and MutL to function at peak efficiency. The
      biochemical roles of most of these proteins in the VSP repair pathway have been
      studied extensively. However, these proteins have not been studied together in
      the context of VSP repair in an in vitro system. Using purified components of the
      VSP repair system in a reconstitution reaction, we have begun to develop an
      understanding of the role played by each of these proteins in the VSP repair
      pathway and have gained insights into their interactions. In this report we
      demonstrate an in vitro reconstitution of the VSP repair pathway using a plasmid
      DNA substrate. Surprisingly, the repair track length can be modulated by the
      concentration of DNA ligase. We propose roles for MutL and MutS in coordination
      of this repair pathway.

PMID- 22846990
TI  - Rabex-5 protein regulates the endocytic trafficking pathway of ubiquitinated
      neural cell adhesion molecule L1.
AB  - Ubiquitination of integral membrane proteins is a common posttranslational
      modification used to mediate endocytosis and endocytic sorting of cell surface
      proteins in eukaryotic cells. Ubiquitin (Ub)-binding proteins (UBPs) regulate the
      stability, function, and localization of ubiquitinated cell surface proteins in
      the endocytic pathway. Here, I report that the immunoglobulin superfamily cell
      adhesion molecule L1 undergoes ubiquitination and dephosphorylation on the plasma
      membrane upon L1 antibody-induced clustering, which mimics L1-L1 homophilic
      binding, and that these modifications are critical for obtaining the maximal rate
      of internalization and trafficking to the lysosome, but not to the proteasome.
      Notably, L1 antibody-induced clustering leads to the association of ubiquitinated
      L1 with Rabex-5, a UBP and guanine nucleotide exchange factor for Rab5, via
      interaction with the motif interacting with Ub (MIU) domain, but not the A20-type
      zinc finger domain. This interaction specifically depends on the presence of an
      Ub moiety on lysine residues in L1. Rabex-5 expression accelerates the
      internalization rates of L1(WT) and L1(Y1176A), a tyrosine-based motif mutant,
      but not L1(K11R), an ubiquitination-deficient mutant, leading to the accumulation
      of ubiquitinated L1 on endosomes. In contrast, RNA interference-mediated
      knockdown of Rabex-5 impairs the internalizations of L1(WT) and L1(Y1176A), but
      not L1(K11R) from the plasma membrane. Overall, these results provide a novel
      mechanistic insight into how Rabex-5 regulates internalization and postendocytic
      trafficking of ubiquitinated L1 destined for lysosomal degradation.

PMID- 22846991
TI  - Modulation of constitutive activity and signaling bias of the ghrelin receptor by
      conformational constraint in the second extracellular loop.
AB  - Based on a rare, natural Glu for Ala-204(C+6) variant located six residues after
      the conserved Cys residue in extracellular loop 2b (ECL2b) associated with
      selective elimination of the high constitutive signaling of the ghrelin receptor,
      this loop was subjected to a detailed structure functional analysis. Introduction
      of Glu in different positions demonstrated that although the constitutive
      signaling was partly reduced when introduced in position 205(C+7) it was only
      totally eliminated in position 204(C+6). No charge-charge interaction partner
      could be identified for the Glu(C+6) variant despite mutational analysis of a
      number of potential partners in the extracellular loops and outer parts of the
      transmembrane segments. Systematic probing of position 204(C+6) with amino acid
      residues of different physicochemical properties indicated that a positively
      charged Lys surprisingly provided phenotypes similar to those of the negatively
      charged Glu residue. Computational chemistry analysis indicated that the
      propensity for the C-terminal segment of extracellular loop 2b to form an
      extended alpha-helix was increased from 15% in the wild type to 89 and 82% by
      introduction in position 204(C+6) of a Glu or a Lys residue, respectively.
      Moreover, the constitutive activity of the receptor was inhibited by Zn(2+)
      binding in an engineered metal ion site, stabilizing an alpha-helical
      conformation of this loop segment. It is concluded that the high constitutive
      activity of the ghrelin receptor is dependent upon flexibility in the C-terminal
      segment of extracellular loop 2 and that mutations or ligand binding that
      constrains this segment and thereby conceivably the movements of transmembrane
      domain V relative to transmembrane domain III inhibits the high constitutive
      signaling.

PMID- 22846992
TI  - A key agonist-induced conformational change in the cannabinoid receptor CB1 is
      blocked by the allosteric ligand Org 27569.
AB  - Allosteric ligands that modulate how G protein-coupled receptors respond to
      traditional orthosteric drugs are an exciting and rapidly expanding field of
      pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569,
      exhibits an intriguing effect; it increases agonist binding, yet blocks agonist
      induced CB1 signaling. Here we explored the mechanism behind this behavior, using
      a site-directed fluorescence labeling approach. Our results show that Org 27569
      blocks conformational changes in CB1 that accompany G protein binding and/or
      activation, and thus inhibit formation of a fully active CB1 structure. The
      underlying mechanism behind this behavior is that simultaneous binding of Org
      27569 produces a unique agonist-bound conformation, one that may resemble an
      intermediate structure formed on the pathway to full receptor activation.

PMID- 22846994
TI  - Theoretical investigation on the binding specificity of sialyldisaccharides with
      hemagglutinins of influenza A virus by molecular dynamics simulations.
AB  - Recognition of cell-surface sialyldisaccharides by influenza A hemagglutinin (HA)
      triggers the infection process of influenza. The changes in glycosidic torsional
      linkage and the receptor conformations may alter the binding specificity of HAs
      to the sialylglycans. In this study, 10-ns molecular dynamics simulations were
      carried out to examine the structural and dynamic behavior of the HAs bound with
      sialyldisaccharides Neu5Acalpha(2-3)Gal (N23G) and Neu5Acalpha(2-6)Gal (N26G).
      The analysis of the glycosidic torsional angles and the pair interaction energy
      between the receptor and the interacting residues of the binding site reveal that
      N23G has two binding modes for H1 and H5 and a single binding mode for H3 and H9.
      For N26G, H1 and H3 has two binding modes, and H5 and H9 has a single binding
      mode. The direct and water-mediated hydrogen bonding interactions between the
      receptors and HAs play dominant roles in the structural stabilization of the
      complexes. It is concluded from pair interaction energy and Molecular Mechanic
      Poisson-Boltzmann Surface Area calculations that N26G is a better receptor for H1
      when compared with N23G. N23G is a better receptor for H5 when compared with
      N26G. However, H3 and H9 can recognize N23G and N26G in equal binding specificity
      due to the marginal energy difference (~2.5 kcal/mol). The order of binding
      specificity of N23G is H3 > H5 > H9 > H1 and N26G is H1 > H3 > H5 > H9,
      respectively. The proposed conformational models will be helpful in designing
      inhibitors for influenza virus.

PMID- 22846993
TI  - The acid-sensitive, anesthetic-activated potassium leak channel, KCNK3, is
      regulated by 14-3-3beta-dependent, protein kinase C (PKC)-mediated endocytic
      trafficking.
AB  - The acid-sensitive neuronal potassium leak channel, KCNK3, is vital for setting
      the resting membrane potential and is the primary target for volatile
      anesthetics. Recent reports demonstrate that KCNK3 activity is down-regulated by
      PKC; however, the mechanisms responsible for PKC-induced KCNK3 down-regulation
      are undefined. Here, we report that endocytic trafficking dynamically regulates
      KCNK3 activity. Phorbol esters and Group I metabotropic glutamate receptor
      (mGluR) activation acutely decreased both native and recombinant KCNK3 currents
      with concomitant KCNK3 surface losses in cerebellar granule neurons and cell
      lines. PKC-mediated KCNK3 internalization required the presence of both 14-3
      3beta and a novel potassium channel endocytic motif, because depleting either 14
      3-3beta protein levels or ablating the endocytic motif completely abrogated PKC
      regulated KCNK3 trafficking. These results demonstrate that neuronal potassium
      leak channels are not static membrane residents but are subject to 14-3-3beta
      dependent regulated trafficking, providing a straightforward mechanism to
      modulate neuronal excitability and synaptic plasticity by Group I mGluRs.

PMID- 22846996
TI  - The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by
      CD277/butyrophilin-3 (BTN3A)-specific antibodies.
AB  - Human Vgamma9Vdelta2 T cells are well known for their rapid and potent response
      to infection and tumorigenesis when in the presence of endogenous or exogenous
      phosphoisoprenoids. However, the molecular mechanisms behind the activation of
      this gammadelta T cell population remains unclear. Evidence pointing to a role
      for the CD277/butyrophilin-3 (BTN3A) molecules in this response led us to
      investigate the structures of these molecules and their modifications upon
      binding to an agonist antibody (20.1) that mimics phosphoisoprenoid-mediated
      Vgamma9Vdelta2 activation and an antagonist antibody (103.2) that inhibits this
      reactivity. We find that the three BTN3A isoforms: BTN3A1, BTN3A2, and BTN3A3,
      have high structural homology to the B7 superfamily of proteins and exist as V
      shaped homodimers in solution, associating through the membrane proximal C-type
      Ig domain. The 20.1 and 103.2 antibodies bind to separate epitopes on the BTN3A
      Ig-V domain with high affinity but likely with different valencies based on their
      binding orientation. These structures directly complement functional studies of
      this system that demonstrate that BTN3A1 is necessary for Vgamma9Vdelta2
      activation and begin to unravel the extracellular events that occur during
      stimulation through the Vgamma9Vdelta2 T cell receptor.

PMID- 22846995
TI  - Galectin-3 protein regulates mobility of N-cadherin and GM1 ganglioside at cell
      cell junctions of mammary carcinoma cells.
AB  - Galectin-3 binding to cell surface glycoproteins, including branched N-glycans
      generated by N-acetylglucosaminyltransferase V (Mgat5) activity, forms a
      multivalent, heterogeneous, and dynamic lattice. This lattice has been shown to
      regulate integrin and receptor tyrosine kinase signaling promoting tumor cell
      migration. N-cadherin is a homotypic cell-cell adhesion receptor commonly
      overexpressed in tumor cells that contributes to cell motility. Here we show that
      galectin-3 and N-cadherin interact and colocalize with the lipid raft marker GM1
      ganglioside in cell-cell junctions of mammary epithelial cancer cells. Disruption
      of the lattice by deletion of Mgat5, siRNA depletion of galectin-3, or
      competitive inhibition with lactose stabilizes cell-cell junctions. It also
      reduces, in a p120-catenin-dependent manner, the dynamic pool of junctional N
      cadherin. Proteomic analysis of detergent-resistant membranes (DRMs) revealed
      that the galectin lattice opposes entry of many proteins into DRM rafts. N
      cadherin and catenins are present in DRMs; however, their DRM distribution is not
      significantly affected by lattice disruption. Galectin lattice integrity
      increases the mobile fraction of the raft marker, GM1 ganglioside binding cholera
      toxin B subunit Ctb, at cell-cell contacts in a p120-catenin-independent manner,
      but does not affect the mobility of either Ctb-labeled GM1 or GFP-coupled N
      cadherin in nonjunctional regions. Our results suggest that the galectin lattice
      independently enhances lateral molecular diffusion by direct interaction with
      specific glycoconjugates within the adherens junction. By promoting exchange
      between raft and non-raft microdomains as well as molecular dynamics within
      junction-specific raft microdomains, the lattice may enhance turnover of N
      cadherin and other glycoconjugates that determine junctional stability and rates
      of cell migration.

PMID- 22846997
TI  - Nuclear-to-cytoplasmic relocalization of the proliferating cell nuclear antigen
      (PCNA) during differentiation involves a chromosome region maintenance 1 (CRM1)
      dependent export and is a prerequisite for PCNA antiapoptotic activity in mature
      neutrophils.
AB  - Neutrophils are deprived of proliferative capacity and have a tightly controlled
      lifespan to avoid their persistence at the site of injury. We have recently
      described that the proliferating cell nuclear antigen (PCNA), a nuclear factor
      involved in DNA replication and repair of proliferating cells, is a key regulator
      of neutrophil survival. In neutrophils, PCNA was localized exclusively in the
      cytoplasm due to its nuclear-to-cytoplasmic relocalization during granulocytic
      differentiation. We showed here that leptomycin B, an inhibitor of the chromosome
      region maintenance 1 (CRM1) exportin, inhibited PCNA relocalization during
      granulocytic differentiation of HL-60 and NB4 promyelocytic cell lines and of
      human CD34(+) primary cells. Using enhanced green fluorescent protein fusion
      constructs, we have demonstrated that PCNA relocalization involved a nuclear
      export signal (NES) located from Ile-11 to Ile-23 in the PCNA sequence. However,
      this NES, located at the inner face of the PCNA trimer, was not functional in
      wild-type PCNA, but instead, was fully active and leptomycin B-sensitive in the
      monomeric PCNAY114A mutant. To test whether a defect in PCNA cytoplasmic
      relocalization would affect its antiapoptotic activity in mature neutrophils, a
      chimeric PCNA fused with the SV40 nuclear localization sequence (NLS) was
      generated to preclude its cytoplasmic localization. As expected, neutrophil
      differentiated PLB985 cells expressing ectopic SV40NLS-PCNA had an increased
      nuclear PCNA as compared with cells expressing wild-type PCNA. Accordingly, the
      nuclear PCNA mutant did not show any antiapoptotic activity as compared with wild
      type PCNA. Nuclear-to-cytoplasmic relocalization that occurred during myeloid
      differentiation is essential for PCNA antiapoptotic activity in mature
      neutrophils and is dependent on the newly identified monomerization-dependent
      PCNA NES.

PMID- 22846998
TI  - Trans-infection but not infection from within endosomal compartments after cell
      to-cell HIV-1 transfer to CD4+ T cells.
AB  - Cellular contacts between HIV-1-infected donor cells and uninfected primary
      CD4(+) T lymphocytes lead to virus transfer into endosomes. Recent evidence
      suggests that HIV particles may fuse with endosomal membranes to initiate a
      productive infection. To explore the role of endocytosis in the entry and
      replication of HIV, we evaluated the infectivity of transferred HIV particles in
      a cell-to-cell culture model of virus transmission. Endocytosed virus led to
      productive infection of cells, except when cells were cultured in the presence of
      the anti-gp120 mAb IgGb12, an agent that blocks virus attachment to CD4,
      suggesting that endocytosed virus was recycled to the outer cell surface.
      Confocal microscopy confirmed the colocalization of internalized virus antigen
      and the endosomal marker dynamin. Additionally, virus transfer, fusion, or
      productive infection was not blocked by dynasore, dynamin-dependent endosome
      scission inhibitor, at subtoxic concentrations, suggesting that the early capture
      of virus into intracellular compartments did not depend on endosomal maturation.
      Our results suggest that endocytosis is not a mechanism of infection of primary
      CD4 T cells, but may serve as a reservoir capable of inducing trans-infection of
      cells after the release of HIV particles to the extracellular environment.

PMID- 22846999
TI  - A quartet of leucine residues in the guanylate kinase domain of CaVbeta
      determines the plasma membrane density of the CaV2.3 channel.
AB  - Ca(V)beta subunits are formed by a Src homology 3 domain and a guanylate kinase
      like (GK) domain connected through a variable HOOK domain. Complete deletion of
      the Src homology 3 domain (75 residues) as well as deletion of the HOOK domain
      (47 residues) did not alter plasma membrane density of Ca(V)2.3 nor its typical
      activation gating. In contrast, six-residue deletions in the GK domain disrupted
      cell surface trafficking and functional expression of Ca(V)2.3. Mutations of
      residues known to carry nanomolar affinity binding in the GK domain of Ca(V)beta
      (P175A, P179A, M195A, M196A, K198A, S295A, R302G, R307A, E339G, N340G, and A345G)
      did not significantly alter cell surface targeting or gating modulation of
      Ca(V)2.3. Nonetheless, mutations of a quartet of leucine residues (either single
      or multiple mutants) in the alpha3, alpha6, beta10, and alpha9 regions of the GK
      domain were found to significantly impair cell surface density of Ca(V)2.3
      channels. Furthermore, the normalized protein density of Ca(V)2.3 was nearly
      abolished with the quadruple Ca(V)beta3 Leu mutant L200G/L303G/L337G/L342G.
      Altogether, our observations suggest that the four leucine residues in Ca(V)beta3
      form a hydrophobic pocket surrounding key residues in the alpha-interacting
      domain of Ca(V)2.3. This interaction appears to play an essential role in
      conferring Ca(V)beta-induced modulation of the protein density of Ca(V)alpha1
      subunits in Ca(V)2 channels.

PMID- 22847001
TI  - Betaine homocysteine methyltransferase is active in the mouse blastocyst and
      promotes inner cell mass development.
AB  - Methyltransferases are an important group of enzymes with diverse roles that
      include epigenetic gene regulation. The universal donor of methyl groups for
      methyltransferases is S-adenosylmethionine (AdoMet), which in most cells is
      synthesized using methyl groups carried by a derivative of folic acid. Another
      mechanism for AdoMet synthesis uses betaine as the methyl donor via the enzyme
      betaine-homocysteine methyltransferase (BHMT, EC 2.1.1.5), but it has been
      considered to be significant only in liver. Here, we show that mouse
      preimplantation embryos contain endogenous betaine; Bhmt mRNA is first expressed
      at the morula stage; BHMT is abundant at the blastocyst stage but not other
      preimplantation stages, and BHMT activity is similarly detectable in blastocyst
      homogenates but not those of two-cell or morula stage embryos. Knockdown of BHMT
      protein levels and reduction of enzyme activity using Bhmt-specific antisense
      morpholinos or a selective BHMT inhibitor resulted in decreased development of
      embryos to the blastocyst stage in vitro and a reduction in inner cell mass cell
      number in blastocysts. The detrimental effects of BHMT knockdown were fully
      rescued by the immediate methyl-carrying product of BHMT, methionine. A
      physiological role for betaine and BHMT in blastocyst viability was further
      indicated by increased fetal resorption following embryo transfer of BHMT
      knockdown blastocysts versus control. Thus, mouse blastocysts are unusual in
      being able to generate AdoMet not only by the ubiquitous folate-dependent
      mechanism but also from betaine metabolized by BHMT, likely a significant pool of
      methyl groups in blastocysts.

PMID- 22847000
TI  - Curcumin inhibits Rift Valley fever virus replication in human cells.
AB  - Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select
      agent, an emerging infectious virus, and an agricultural pathogen. Understanding
      RVFV-host interactions is imperative to the design of novel therapeutics. Here,
      we report that an infection by the MP-12 strain of RVFV induces phosphorylation
      of the p65 component of the NFkappaB cascade. We demonstrate that phosphorylation
      of p65 (serine 536) involves phosphorylation of IkappaBalpha and occurs through
      the classical NFkappaB cascade. A unique, low molecular weight complex of the IKK
      beta subunit can be observed in MP-12-infected cells, which we have labeled IKK
      beta2. The IKK-beta2 complex retains kinase activity and phosphorylates an
      IkappaBalpha substrate. Inhibition of the IKK complex using inhibitors impairs
      viral replication, thus alluding to the requirement of an active IKK complex to
      the viral life cycle. Curcumin strongly down-regulates levels of extracellular
      infectious virus. Our data demonstrated that curcumin binds to and inhibits
      kinase activity of the IKK-beta2 complex in infected cells. Curcumin partially
      exerts its inhibitory influence on RVFV replication by interfering with IKK-beta2
      mediated phosphorylation of the viral protein NSs and by altering the cell cycle
      of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully
      virulent version of RVFV. Curcumin treatment down-regulated viral replication in
      the liver of infected animals. Our data point to the possibility that RVFV
      infection may result in the generation of novel versions of host components (such
      as IKK-beta2) that, by virtue of altered protein interaction and function,
      qualify as unique therapeutic targets.

PMID- 22847002
TI  - Clostridium perfringens alpha-toxin recognizes the GM1a-TrkA complex.
AB  - Clostridium perfringens alpha-toxin is the major virulence factor in the
      pathogenesis of gas gangrene. Alpha-toxin is a 43-kDa protein with two structural
      domains; the N-domain contains the catalytic site and coordinates the divalent
      metal ions, and the C-domain is a membrane-binding site. The role of the exposed
      loop region (72-93 residues) in the N-domain, however, has been unclear. Here we
      show that this loop contains a ganglioside binding motif (H ... SXWY ... G) that
      is the same motif seen in botulinum neurotoxin and directly binds to a specific
      conformation of the ganglioside Neu5Acalpha2-3(Galbeta1-3GalNAcbeta1-4)Galbeta1
      4Glcbeta1Cer (GM1a) through a carbohydrate moiety. Confocal microscopy analysis
      using fluorescently labeled BODIPY-GM1a revealed that the toxin colocalized with
      GM1a and induced clustering of GM1a on the cell membranes. Alpha-toxin was only
      slightly toxic in beta1,4-N-acetylgalactosaminyltransferase knock-out mice, which
      lack the a-series gangliosides that contain GM1a, but was highly toxic in
      alpha2,8-sialyltransferase knock-out mice, which lack both b-series and c-series
      gangliosides, similar to the control mice. Moreover, experiments with site
      directed mutants indicated that Trp-84 and Tyr-85 in the exposed alpha-toxin loop
      play an important role in the interaction with GM1a and subsequent activation of
      TrkA. These results suggest that binding of alpha-toxin to GM1a facilitates the
      activation of the TrkA receptor and induces a signal transduction cascade that
      promotes the release of chemokines. Therefore, we conclude that GM1a is the
      primary cellular receptor for alpha-toxin, which can be a potential target for
      drug developed against this pathogen.

PMID- 22847003
TI  - Heat shock factor Hsf1 cooperates with ErbB2 (Her2/Neu) protein to promote
      mammary tumorigenesis and metastasis.
AB  - ErbB2/Neu oncogene is overexpressed in 25% of invasive/metastatic breast cancers.
      We have found that deletion of heat shock factor Hsf1 in mice overexpressing
      ErbB2/Neu significantly reduces mammary tumorigenesis and metastasis. Hsf1(+/
      )ErbB2/Neu(+) tumors exhibit reduced cellular proliferative and invasive
      properties associated with reduced activated ERK1/2 and reduced epithelial
      mesenchymal transition (EMT). Hsf1(+/+)Neu(+) mammary epithelial cells exposed to
      TGFbeta show high levels of ERK1/2 activity and EMT; this is associated with
      reduced expression of E-cadherin and increased expression of Slug and vimentin, a
      mesenchymal marker. In contrast, Hsf1(-/-)Neu(+) or Hsf1(+/+)Neu(+) cells do not
      exhibit activated ERK1/2 and show reduced EMT in the presence of TGFbeta. The
      ineffective activation of the RAS/RAF/MEK/ERK1/2 signaling pathway in cells with
      reduced levels of HSF1 is due to the low levels of HSP90 in complex with RAF1
      that are required for RAF1 stability and maturation. These results indicate a
      powerful inhibitory effect conferred by HSF1 downstream target genes in the
      inhibition of ErbB2-induced breast cancers in the absence of the Hsf1 gene.

PMID- 22847009
TI  - Ratiometric nanomolar detection of Cu2+ ions in mixed aqueous media: a Cu2+/Li+
      ions switchable allosteric system based on thiacalix[4]crown.
AB  - A novel ditopic fluorescent chemosensor 2, based on the 1,3-alternate
      conformation of thiacalix[4]crown possessing two complexation sites, was
      synthesized and shows ratiometric nanomolar detection of Cu(2+) ions and exhibits
      negative allosteric behaviour between Cu(2+)/Li(+) ions in mixed aqueous media.

PMID- 22847010
TI  - Spermiogenesis and the spermatozoon ultrastructure of Robphildollfusium fractum
      (Digenea: Gyliauchenidae), an intestinal parasite of Sarpa salpa (Pisces:
      Teleostei).
AB  - Spermiogenesis in Robphildollfusium fractum begins with the formation of a
      differentiation zone containing: two centrioles, each bearing striated rootlets,
      nucleus, several mitochondria and an intercentriolar body constituted by seven
      electron-dense layers. The two centrioles originate two free flagella growing
      orthogonally to the median cytoplasmic process. Later, the free flagella rotate
      and undergo proximodistal fusion with the median cytoplasmic process. Nuclear and
      mitochondrial migrations occur before this proximodistal fusion. Finally, the
      young spermatozoon detaches from the residual cytoplasm after the constriction of
      the ring of arched membranes. The spermatozoon of R. fractum exhibits two
      axonemes of different length of the 9+'1' trepaxonematan pattern, nucleus, two
      mitochondria, two bundles of parallel cortical microtubules, external
      ornamentation of the plasma membrane, spine-like bodies and granules of glycogen.
      Additionally, a shorter axoneme, which does not reach the nuclear region, the
      presence of an electron-dense material in the anterior spermatozoon extremity and
      the morphologies of both spermatozoon extremities characterize the mature sperm
      of R. fractum.

PMID- 22847011
TI  - Immunolocalization of hepatic estrogen and progesterone receptors in the female
      lizard Uromastyx acanthinura.
AB  - The hormonal regulation of hepatic synthesis of vitellogenin during the annual
      reproductive cycle was performed for the first time in the deserticole,
      oviparous, diurnal and herbivorous Uromastyx acanthinura, a lizard belonging to
      the Agamidae family. In order to elucidate what kind of estrogen receptor is
      involved in this process, an immunohistochemical study was performed. Changes
      were obtained in the labeling and cellular distribution of the estrogen and
      progesterone receptors according to the period of the reproductive cycle and the
      experimental administration of 17beta-estradiol. Only the ERbeta subtype was
      present; it was found in all phases of the cycle with a variable localization:
      nuclear and cytosolic during vitellogenesis, mainly cytosolic in the female with
      egg retention (luteal phase) and strictly cytosolic in females at sexual rest.
      The progesterone receptors were present only at the luteal phase and during
      sexual rest and disappeared completely from females after 17beta-estradiol
      treatment in sexual rest. Our data suggested that mediation of action of the
      17beta-estradiol in the vitellogenin synthesis in the lizard U. acanthinura
      occured via ERbeta. PRA and PRB could both be necessary for the negative effect
      of progesterone on the hepatic synthesis of vitellogenin.

PMID- 22847012
TI  - Adult hematopoietic progenitors are multipotent in chimeric mice.
AB  - Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency
      (iPSCs), can differentiate into multiple cell lineages. We previously reported
      that adult mammalian bone marrow contains a sub-population of CD34+ cells that
      express genes of ESCs and genes required to generate iPSCs. They also express
      lineage genes of the three embryonic germ layers. Are these CD34+ cells
      multipotent? Here, CD34+ bone marrow stem cells from adult male ROSA mice, which
      carry two markers: the beta-galactosidase gene and the male Y chromosome, were
      transplanted into blastocysts of wildtype mice. Each female ROSA chimera
      generated had a distinct pattern of male-derived organs expressing beta
      galactosidase; e.g., ectodermal brain, dorsal root ganglia and skin; mesodermal
      heart, bone and bone marrow; and endodermal pancreas, intestine, and liver. Thus,
      adult mammals carry cells that appear to exhibit a developmental potential
      reminiscent of ESCs and iPSCs suggesting they could be used for cell replacement
      therapy.

PMID- 22847013
TI  - Alteration of dopaminergic innervation and voluntary movements after long period
      of thirst in a semi-desert rodent, Meriones shawi: behavioral and
      immunohistochemical studies.
AB  - Dehydration is a powerful stimulus causing disequilibrium in homeostasis of water
      and electrolytes resulting from depletion in total body water. Most studies have
      focused on domestic and laboratory animals; however, the study of desert animals
      allows improved understanding about water balance and resistance to dehydration
      and associated behavioral changes, including those related to voluntary
      movements. Meriones shawi (Shaw's Jird) is a desert rodent characterized by its
      resistance to long periods of thirst that can extend for several months. In the
      present study, M. shawi were subjected to water deprivation for 1month. We used
      tyrosine hydroxylase immunohistochemistry (TH: the key enzyme of catecholamine
      biosynthesis) to evaluate the effects of prolonged dehydration on the
      dopaminergic system in both substancia nigra pars compacta and ventral tegmental
      area (SNpc and VTA), which are the main sources of dopamine input to several
      brain areas; the immunolabelling was performed also in both the medial forebrain
      bundle and the caudate putamen (striatum). In addition, the open-field test was
      used to evaluate the effect of dehydration on locomotor activity in M. shawi. The
      results showed an increase in TH immunolabelling in both SNpc and VTA following
      1month of dehydration compared to control levels. The same results were obtained
      with fibers in both MFB and striatum. This augmentation of TH immunoreactivity
      was accompanied by noticeable changes in locomotor activity behavior of Meriones,
      the recording test shows the hyperactivity of animals which is probably caused by
      dehydration. Overall, the results indicate that dehydration is able to increase
      dopaminergic neurotransmission, which might be involved in generating
      hyperactivity in this desert animal.

PMID- 22847017
TI  - Identifying research needs for improving health care.
AB  - Insights from systematic reviews can help new studies better meet the priorities
      and needs of patients and communities. However, systematic reviews unfortunately
      have not yet achieved this position to direct and guide new research studies. The
      Agency for Healthcare Research and Quality's Evidence-based Practice Center
      Program uses systematic reviews to identify gaps in current evidence and has
      developed a systematic process of prioritizing these gaps with stakeholder input
      into clearly defined "future research needs." Eight Evidence-based Practice
      Centers began to apply this effort in 2010 to various clinical and policy topics.
      Gaps that prevented systematic reviewers from answering central questions of the
      review may include insufficient studies on subpopulations, insufficient studies
      with appropriate comparators, lack of appropriate outcomes measured, and methods
      problems. Stakeholder panels, consisting of advocacy groups, patients,
      researchers, clinicians, funders, and policymakers, help refine the gaps through
      multiple conference calls and prioritization exercises. Each report highlights a
      focused set of 4 to 15 high-priority needs with an accompanying description of
      possible considerations for study design. Identification of high-priority
      research needs could potentially speed the development and implementation of high
      priority, stakeholder-engaged research.

PMID- 22847015
TI  - Metallothionein primary structure in amphibians: Insights from comparative
      evolutionary analysis in vertebrates.
AB  - Metallothioneins are cysteine-rich, low-molecular weight metal-binding proteins
      ubiquitously expressed in living organisms. In the last past years, the
      increasing amount of vertebrate non-mammalian metallothionein sequences available
      have disclosed for these proteins differences in the primary structure that have
      not been supposed before. To provide a more up-to-date view of the
      metallothioneins in non-mammalian tetrapods, we decided to increase the still
      scarce knowledge concerning the primary structure and the evolution of
      metallothioneins in amphibians. Our data demonstrate an unexpected diversity of
      metallothionein sequences among amphibians, accompanied by remarkable features in
      their phylogeny. Phylogenetic analysis also reveals the complexity of vertebrate
      metallothionein evolution, made by both ancient and more recent events of gene
      duplication and loss.

PMID- 22847014
TI  - Identification of ancient Olea europaea L. and Cornus mas L. seeds by DNA
      barcoding.
AB  - The analysis of ancient DNA (aDNA) provides archaeologists and anthropologists
      with innovative, scientific and accurate data to study and understand the past.
      In this work, ancient seeds, found in the "Mora Cavorso" archaeological site
      (Latium, Central Italy), were analyzed to increase information about Italian
      Neolithic populations (plant use, agriculture, diet, trades, customs and
      ecology). We performed morphological and genetic techniques to identify fossil
      botanical species. In particular, this study also suggests and emphasizes the use
      of DNA barcode method for ancient plant sample analysis. Scanning electron
      microscope (SEM) observations showed seed compact structure and irregular surface
      but they did not permit a precise nor empirical classification: so, a molecular
      approach was necessary. DNA was extracted from ancient seeds and then it was
      used, as template, for PCR amplifications of standardized barcode genes. Although
      aDNA could be highly degraded by the time, successful PCR products were obtained,
      sequenced and compared to nucleotide sequence databases. Positive outcomes
      (supported by morphological comparison with modern seeds, geographical
      distribution and historical data) indicated that seeds could be identified as
      belonging to two plant species: Olea europaea L. and Cornus mas L.

PMID- 22847016
TI  - When colour patterns reflect phylogeography: new species of Dasypeltis
      (Serpentes: Colubridae: Boigini) from West Africa.
AB  - Six colour phases are currently known in the genus Dasypeltis in West Africa,
      three in the D. scabra complex and three in the D. fasciata complex. Molecular
      phylogenetic analysis reveals that all correspond to distinct species. D.
      parascabra sp. nov. is described from wet savannah areas of Guinea and Ivory
      Coast. D. latericia is given full specific rank. The validity of D. sahelensis,
      D. gansi and D. confusa - three species recently described on the basis of colour
      pattern and biogeography - is confirmed. D. fasciata is confined to rain forest
      areas of West and Central Africa. D. scabra is absent from West Africa.

PMID- 22847018
TI  - Diagnosing and quantification of acute alcohol intoxication--comparison of dual
      energy CT with biochemical analysis: initial experience.
AB  - PURPOSE: To quantify the correlation between fat content of an acute alcohol
      intoxication and the difference of computer tomography attenuation value in dual
      energy CT in comparison to biochemical triglyceride analysis and to evaluate
      qualitatively the value of DECT in the diagnosis of fatty liver caused by ethanol
      dosage in rats. MATERIALS AND METHODS: DECT at 140 kV and 80 kV was performed on
      20 rats before and two days after the administration of 3 ml of 50% ethanol. The
      CT attenuation value in the livers at 140 kV, 80 kV and the differences between
      them in Hounsfield units (DeltaH) were collected. Parts of the liver (100 mg)
      were measured in biochemical triglyceride analysis as the reference standard. A
      blood sample was also taken to measure specific liver enzymes. RESULTS: Linear
      correlation between biochemical triglyceride analysis and CT density of DeltaH
      was found (r=0.949). 140 kV attenuation data were between 44 HU and 61.3 HU, 80
      kV attenuation data were between 58.4 HU and 64.7 HU, and DeltaH data were
      between 3.4 HU and 14.4 HU (p<=0.037). The biochemical triglyceride analysis data
      were between 7.1 mg/g and 41.1 mg/g. The hepatic enzymes serum aspartate (ASAT)
      aminotransferase and alanine aminotransferase (ALAT) were elevated in all rats.
      ASAT correlated directly with DeltaHU (r=-0.86). CONCLUSION: DECT provides a non
      invasive method to determine and evaluate hepatic fat content after acute alcohol
      intoxication. It provides the possibility to detect and quantify the hepatic fat
      content of liver graft.

PMID- 22847006
TI  - Filament formation of the FtsZ/tubulin-like protein TubZ from the Bacillus cereus
      pXO1 plasmid.
AB  - Stable maintenance of low-copy-number plasmids requires partition (par) systems
      that consist of a nucleotide hydrolase, a DNA-binding protein, and a cis-acting
      DNA-binding site. The FtsZ/tubulin-like GTPase TubZ was identified as a
      partitioning factor of the virulence plasmids pBtoxis and pXO1 in Bacillus
      thuringiensis and Bacillus anthracis, respectively. TubZ exhibits high GTPase
      activity and assembles into polymers both in vivo and in vitro, and its
      "treadmilling" movement is required for plasmid stability in the cell. To
      investigate the molecular mechanism of pXO1 plasmid segregation by TubZ
      filaments, we determined the crystal structures of Bacillus cereus TubZ in apo-,
      GDP-, and guanosine 5'-3-O-(thio)triphosphate (GTPgammaS)-bound forms at
      resolutions of 2.1, 1.9, and 3.3 A, respectively. Interestingly, the slowly
      hydrolyzable GTP analog GTPgammaS was hydrolyzed to GDP in the crystal. In the
      post-GTP hydrolysis state, GDP-bound B. cereus TubZ forms a dimer by the head-to
      tail association of individual subunits in the asymmetric unit, which is similar
      to the protofilament formation of FtsZ and B. thuringiensis TubZ. However, the M
      loop interacts with the nucleotide-binding site of the adjacent subunit and
      stabilizes the filament structure in a different manner, which indicates that the
      molecular assembly of the TubZ-related par systems is not stringently conserved.
      Furthermore, we show that the C-terminal tail of TubZ is required for association
      with the DNA-binding protein TubR. Using a combination of crystallography, site
      directed mutagenesis, and biochemical analysis, our results provide the
      structural basis of the TubZ polymer that may drive DNA segregation.

PMID- 22847019
TI  - Synthesis and one-electron reduction characteristics of radiation-activated
      prodrugs possessing two 5-fluorodeoxyuridine units.
AB  - Two molecules of an antitumor agent, 5-fluorodeoxyuridine (5-FdUrd), were
      connected by a 2-oxoalkyl linker (Oxo-linker) at the N(3) position to obtain
      radiation-activated prodrugs, FdUrd(2) A and FdUrd(2) B. The prodrugs in this
      study released 5-FdUrd via one-electron reduction initiated by hypoxic X
      irradiation. The release of 5-FdUrd from FdUrd(2) A and FdUrd(2) B proceeded more
      efficiently than that of previous prodrug, Oxo-FdUrd, which possessed one
      molecule of 5-FdUrd. FdUrd(2) A exhibited increased cytotoxicity against A549
      cells when the FdUrd(2) A solution had been irradiated with a large dose of X
      rays before administration to the cells. However, we observed no effect on
      cytotoxicity when the cells were X-irradiated under hypoxic conditions in the
      presence of FdUrd(2) A because the amount of 5-FdUrd released in the cells seemed
      to be too low to induce cytotoxic activity.

PMID- 22847021
TI  - Endoscopic anatomy of sellar region.
AB  - The transsphenoidal approach is the preferred access used in surgical treatment
      of most sellar region pathologies. The use of endoscopy is advantageous, and it
      is considered a good alternative to the traditional microsurgical technique. The
      purpose of this study is to recognize and describe anatomical variations of the
      sphenoid sinus and the sellar region, mainly describing the anatomy of the
      posterior wall of the sphenoid sinus and analyzing intercarotid distances in 3
      regions. Thirty sphenoid blocks treated with formaldehyde were injected and
      dissected. Using endoscopy, anatomical variations were studied and the
      intercarotid distances were measured at the tuberculum sellae, sellar floor and
      clivus. The types of sphenoid sinus found were: conchal in 1 (4.76 %), pre-sellar
      in 2 (9.52 %) and sellar in 19 (85.7 %) specimens. The mean distance found from
      the sphenoid sinus ostium to the sella turcica was 19 mm (+/-6.5) mm. The mean
      intercarotid distances found at the tuberculum sellae, sellar floor and clivus
      were respectively 13.32, 18.00 and 18.90 mm. Endoscopy, with its magnification
      and lighting provide a panoramic view of deep fields. The anatomical variations
      described in this study support the need for a careful evaluation of preoperative
      images in each case.

PMID- 22847020
TI  - Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with
      newly diagnosed glioblastoma.
AB  - BACKGROUND: This study evaluated the safety and immune responses to an autologous
      dendritic cell vaccine pulsed with class I peptides from tumor-associated
      antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell
      population (ICT-107). METHODS: TAA epitopes included HER2, TRP-2, gp100, MAGE-1,
      IL13Ralpha2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma
      (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated
      into dendritic cells, pulsed with TAA peptides, and administered intradermally
      three times at two-week intervals. RESULTS: Twenty-one patients were enrolled
      with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one
      brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 %
      responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all
      patient tumors expressed at least three TAA, with 75 % expressing all six.
      Correlations of increased PFS and OS with quantitative expression of MAGE1 and
      AIM-2 were observed, and a trend for longer survival was observed with gp100 and
      HER2 antigens. Target antigens gp100, HER1, and IL13Ralpha2 were downregulated in
      recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133
      expression was seen in five patients who underwent a second resection. At a
      median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of
      tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and
      median OS was 38.4 months. CONCLUSIONS: Expression of four ICT-107 targeted
      antigens in the pre-vaccine tumors correlated with prolonged overall survival and
      PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on
      glioblastoma cancer stem cells is supported by the observation of decreased or
      absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.

PMID- 22847008
TI  - Role of p63 in Development, Tumorigenesis and Cancer Progression.
AB  - The p53-related protein p63 has pleiotropic functions, including cell
      proliferation, survival, apoptosis, differentiation, senescence, and aging. The
      p63 gene is expressed as multiple isoforms that either contain an N-terminal p53
      homologous transactivation domain (TAp63) or that lack this domain (DeltaNp63).
      Multiple studies have demonstrated that p63 plays a crucial role in stratified
      epithelial development, and have shown the importance of p63 for maintaining
      proliferation potential, inducing differentiation, and preventing senescence.
      Additionally, much research focuses on the role of p63 in cancer progression.
      Clinical evidence suggests that p63 may play a role in inhibiting metastasis.
      Similarly, genetic mice models together with cell culture data strongly indicate
      that p63 deficiency may be a causative factor for metastatic spread. Moreover,
      the role of p63 in cancer metastasis has been shown to be greatly related to the
      ability of mutant p53 to promote cancer malignancy. However, there is still much
      confusion as to what the role of each specific isoform is. In this review, we
      highlight some of the major findings in the current literature regarding the role
      of specific p63 isoforms in development, tumorigenesis, and particularly in
      cancer metastasis.

PMID- 22847007
TI  - Interactions of isolated C-terminal fragments of neural Wiskott-Aldrich syndrome
      protein (N-WASP) with actin and Arp2/3 complex.
AB  - Wiskott-Aldrich syndrome proteins (WASP) are a family of proteins that all
      catalyze actin filament branching with the Arp2/3 complex in a variety of actin
      based motile processes. The constitutively active C-terminal domain, called VCA,
      harbors one or more WASP homology 2 (WH2) domains that bind G-actin, whereas the
      CA extension binds the Arp2/3 complex. The VCA.actin.Arp2/3 entity associates
      with a mother filament to form a branched junction from which a daughter filament
      is initiated. The number and function of WH2-bound actin(s) in the branching
      process are not known, and the stoichiometry of the VCA.actin.Arp2/3 complex is
      debated. We have expressed the tandem WH2 repeats of N-WASP, either alone (V) or
      associated with the C (VC) and CA (VCA) extensions. We analyzed the structure of
      actin in complex with V, VC, and VCA using protein crystallography and
      hydrodynamic and spectrofluorimetric methods. The partial crystal structure of
      the VC.actin 1:1 complex shows two actins in the asymmetric unit with extensive
      actin-actin contacts. In solution, each of the two WH2 domains in V, VC, and VCA
      binds G-actin in 1:2 complexes that participate in barbed end assembly. V, VC,
      and VCA enhance barbed end depolymerization like profilin but neither nucleate
      nor sever filaments, in contrast with other WH2 repeats. VCA binds the Arp2/3
      complex in a 1:1 complex even in the presence of a large excess of VCA.
      VCA.Arp2/3 binds one actin in a latrunculin A-sensitive fashion, in a 1:1:1
      complex, indicating that binding of the second actin to VCA is weakened in the
      ternary complex.

PMID- 22847005
TI  - Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression
      leading to self-renewal, clonal formation, and cisplatin resistance in cancer
      stem cells from head and neck squamous cell carcinoma.
AB  - Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer
      associated with major morbidity and mortality. In this study, we determined that
      human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells
      (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1
      (ALDH1) expression. These tumor cells also express several stem cell markers (the
      transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC
      properties of self-renewal/clonal formation and the ability to generate
      heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the
      CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a
      complex formation and the nuclear translocation of three CSC transcription
      factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an
      upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin
      immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302
      expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This
      process results in suppression of several epigenetic regulators (AOF1/AOF2 and
      DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and
      XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These
      CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302
      expression and block its target functions. Our results demonstrate that the anti
      miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but
      also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated
      cancer stem cell functions. Taken together, these findings strongly support the
      contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling
      plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down
      regulation and survival of protein activation. All of these events are critically
      important for the acquisition of cancer stem cell properties, including self
      renewal, clonal formation, and chemotherapy resistance in HA-CD44v3-activated
      head and neck cancer.

PMID- 22847004
TI  - Dynamic structural changes are observed upon collagen and metal ion binding to
      the integrin alpha1 I domain.
AB  - We have applied hydrogen-deuterium exchange mass spectrometry, in conjunction
      with differential scanning calorimetry and protein stability analysis, to examine
      solution dynamics of the integrin alpha1 I domain induced by the binding of
      divalent cations, full-length type IV collagen, or a function-blocking monoclonal
      antibody. These studies revealed features of integrin activation and alpha1I
      ligand complexes that were not detected by static crystallographic data. Mg(2+)
      and Mn(2+) stabilized alpha1I but differed in their effects on exchange rates in
      the alphaC helix. Ca(2+) impacted alpha1I conformational dynamics without
      altering its gross thermal stability. Interaction with collagen affected the
      exchange rates in just one of three metal ion-dependent adhesion site (MIDAS)
      loops, suggesting that MIDAS loop 2 plays a primary role in mediating ligand
      binding. Collagen also induced changes consistent with increased unfolding in
      both the alphaC and allosteric C-terminal helices of alpha1I. The antibody AQC2,
      which binds to alpha1I in a ligand-mimetic manner, also reduced exchange in MIDAS
      loop 2 and increased exchange in alphaC, but it did not impact the C-terminal
      region. This is the first study to directly demonstrate the conformational
      changes induced upon binding of an integrin I domain to a full-length collagen
      ligand, and it demonstrates the utility of the deuterium exchange mass
      spectrometry method to study the solution dynamics of integrin/ligand and
      integrin/metal ion interactions. Based on the ligand and metal ion binding data,
      we propose a model for collagen-binding integrin activation that explains the
      differing abilities of Mg(2+), Mn(2+), and Ca(2+) to activate I domain-containing
      integrins.

PMID- 22847022
TI  - Cold acclimation and BnCBF17-over-expression enhance photosynthetic performance
      and energy conversion efficiency during long-term growth of Brassica napus under
      elevated CO2 conditions.
AB  - The effects of cold acclimation and long-term elevated CO(2) on photosynthetic
      performance of wild-type (WT) and BnCBF17-over-expressing line of Brassica napus
      cv. Westar (BnCBF17-OE) grown at either 20/16  degrees C (non-acclimated) or 5/5 
      degrees C (cold acclimated) and at either ambient (380 MUmol C mol(-1)) or
      elevated (700 MUmol C mol(-1)) CO(2) were studied. Compared with non-acclimated
      WT, the BnCBF17-OE grown at 20  degrees C mimicked the effects of cold
      acclimation on WT B. napus with respect to compact dwarf phenotype and increased
      rates of light-saturated CO(2) assimilation and photosynthetic electron
      transport. This was associated with enhanced energy conversion efficiency into
      biomass as assessed by decreased excitation pressure coupled to decreased
      dependence on non-photochemical energy dissipation for a given irradiance. Growth
      at elevated CO(2) decreased the light and CO(2)-saturated rates of photosynthesis
      by 30 % for non-acclimated WT relative to growth at ambient CO(2). This was
      associated with inhibition in electron transport rates (20 %), decrease in amount
      of rbcL (35 %) and cytosolic FBPase (70 %) and increased excitation pressure and
      non-photochemical quenching in elevated versus ambient CO(2)-grown non-acclimated
      WT. In contrast, light and CO(2)-saturated rates of photosynthesis, electron
      transport, excitation pressure, non-photochemical quenching and levels of rbcL,
      cytosolic FBPase and Lhcb1 were insensitive to growth under elevated CO(2) in
      BnCBF17-OE and cold-acclimated WT. Thus, BnCBF17-over-expression and cold
      acclimation maintain enhanced energy conversion efficiency and reduced
      sensitivity to feedback-limited photosynthesis during long-term growth of B.
      napus under elevated CO(2). Our results indicated that CBFs transcription factors
      regulate not only freezing tolerance but also has major whole plant effects.

PMID- 22847023
TI  - Characterization of a Synechocystis double mutant lacking the photosystem II
      assembly factors YCF48 and Sll0933.
AB  - The de novo assembly of photosystem II (PSII) depends on a variety of assisting
      factors. We have previously shown that two of them, namely, YCF48 and Sll0933,
      mutually interact and form a complex (Rengstl et al. in J Biol Chem 286:21944
      21951, 2011). To gain further insights into the importance of the YCF48/Sll0933
      interaction, an ycf48 ( - ) sll0933 ( - ) double mutant was constructed and its
      phenotype was compared with the single mutants' phenotypes. Analysis of
      fluorescence spectra and oxygen evolution revealed high-light sensitivity not
      only for YCF48 deficient strains but also for sll0933 ( - ), which, in addition,
      showed reduced synthesis and accumulation of newly synthesized CP43 and CP47
      proteins in pulse-labeling experiments. In general, the phenotypic
      characteristics of ycf48 ( - ) sll0933 ( - ) were dominated by the effect of the
      ycf48 deletion and additional inactivation of the sll0933 gene showed only
      negligible additional impairments with regard to growth, absorption spectra and
      accumulation of PSII-related proteins and assembly complexes. In yeast split
      ubiquitin analyses, the interaction between YCF48 and Sll0933 was confirmed and,
      furthermore, support for direct binding of Sll0933 to CP43 and CP47 was obtained.
      Our data provide important new information which further refines our knowledge
      about the PSII assembly process and role of accessory protein factors within it.

PMID- 22847024
TI  - Inhibition of tomato (Solanum lycopersicum L.) root growth by cyanamide is due to
      altered cell division, phytohormone balance and expansin gene expression.
AB  - Cyanamide (CA) has been reported as a natural compound produced by hairy vetch
      (Vicia villosa Roth.) and it was shown also to be an allelochemical, responsible
      for strong allelopathic potential in this species. CA phytotoxicity has been
      demonstrated on various plant species, but to date little is known about its mode
      of action at cellular level. Treatment of tomato (Solanum lycopersicum L.) roots
      with CA (1.2 mM) resulted in inhibition of growth accompanied by alterations in
      cell division, and imbalance of plant hormone (ethylene and auxin) homeostasis.
      Moreover, the phytotoxic effect of CA was also manifested by modifications in
      expansin gene expression, especially in expansins responsible for cell wall
      remodeling after the cytokinesis (LeEXPA9, LeEXPA18). Based on these results the
      phytotoxic activity of CA on growth of roots of tomato seedlings is likely due to
      alterations associated with cell division.

PMID- 22847026
TI  - Genetic dissection of the temperature dependent emergence processes in sorghum
      using a cumulative emergence model and stability parameters.
AB  - Among the major limitations for cultivating biomass sorghum in temperate regions
      is low temperature in spring that results in low and non-uniform emergence. The
      adaptation of sorghum to tropical and subtropical highlands gives hint of genetic
      variation in cold tolerance during emergence. The objective of the present study
      was to detect marker-trait associations for parameters describing the emergence
      process under different temperature regimes. A diversity set comprising 194
      genotypes was tested in nine controlled environments with temperatures ranging
      from 9.4 to 19.9  degrees C. The genotypes were fingerprinted with 171 DArT
      markers. A piecewise linear regression model carried out on cumulative emergence
      was used to estimate genotype mean performance across environments and to carry
      out stability analysis on the parameters of the regression model. Base
      temperature (T (b)) and thermal time required for emergence (E (TS)) were
      determined based on median time to emergence data. Identified QTL positions were
      compared to marker-trait associations for final emergence percentages under low
      (FEP(cold)) and normal (FEP(normal)) temperatures. QTL for mean final emergence
      percentage (FEP), FEP(cold) and FEP(normal,) T (b) and E (TS) were detected on
      SBI-01. Other QTL-rich regions were located on SBI-03, SBI-04, SBI-06, SBI-08,
      and SBI-09. Marker-trait associations for T (b) and E (TS) co-localized to QTL
      for the across environment stability of FEP and the median time to emergence or
      emergence rate, respectively. We conclude that genome regions on six chromosomes
      highly influencing cold tolerance during emergence are promising for regional
      association studies and for the development of stable markers for marker-assisted
      selection.

PMID- 22847028
TI  - Spatial and temporal trends in water quality in a Mediterranean temporary river
      impacted by sewage effluents.
AB  - This paper analyzes how changes in hydrological conditions can affect the water
      quality of a temporary river that receives direct inputs of sewage effluents.
      Data from 12 spatial surveys of the Vene river were examined. Physico-chemical
      parameters, major ion, and nutrient concentrations were measured. Analyses of
      variance (ANOVA) and multivariate analyses were performed. ANOVA revealed
      significant spatial differences for conductivity and major ion but no significant
      spatial differences for nutrient concentrations even if higher average
      concentrations were observed at stations located downstream from sewage effluent
      discharge points. Significant temporal differences were observed among all the
      parameters. Karstic springs had a marked dilution effect on the direct disposal
      of sewage effluents. During high-flow periods, nutrient concentrations were high
      to moderate whereas nutrient concentrations ranged from moderate to bad at
      stations located downstream from the direct inputs of sewage effluents during low
      flow periods. Principal component analysis showed that water quality parameters
      that explained the water quality of the Vene river were highly dependent on
      hydrological conditions. Cluster analysis showed that when the karstic springs
      were flowing, water quality was homogeneous all along the river, whereas when
      karstic springs were dry, water quality at the monitoring stations was more
      fragmented. These results underline the importance of considering hydrological
      conditions when monitoring the water quality of temporary rivers. In view of the
      pollution observed in the Vene river, "good water chemical status" can probably
      only be achieved by improving the management of sewage effluents during low-flow
      periods.

PMID- 22847027
TI  - Antileukemic activity of nuclear export inhibitors that spare normal
      hematopoietic cells.
AB  - Drugs that target the chief mediator of nuclear export, chromosome region
      maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but
      existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic
      effects. Here, we report the structural analysis and antileukemic activity of a
      new generation of small-molecule inhibitors of CRM1. Designated selective
      inhibitors of nuclear export (SINE), these compounds were developed using
      molecular modeling to screen a small virtual library of compounds against the
      nuclear export signal (NES) groove of CRM1. The 2.2-A crystal structure of the
      CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class
      of inhibitors, shows that the drug occupies part of the groove in CRM1 that is
      usually occupied by the NES, but penetrates much deeper into the groove and
      blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic
      activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human
      acute myeloid leukemia (AML) cell lines representing different molecular subtypes
      of the disease. When administered orally to immunodeficient mice engrafted with
      human AML cells, KPT-251 had potent antileukemic activity with negligible
      toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent
      a novel class of drugs that warrant further testing in AML patients.

PMID- 22847029
TI  - Pigmented and depigmented lesions of the ocular fundus.
AB  - PURPOSE OF REVIEW: Pigmented and depigmented ocular fundus lesions (de-POFLs) can
      be isolated and clinically insignificant, or they may be the hallmark of
      associated serious systemic disorders such as familial polyposis. The
      ophthalmologist is often called upon to look for these retinal lesions, or may
      encounter them in the course of routine examination when appropriate medical
      referral becomes essential. RECENT FINDINGS: The ophthalmoscopic and location
      differences between grouped pigmentation of the retinal pigment epithelium (bear
      tracks) and multiple POFLs associated with familial adenomatous polyposis is
      reviewed. The differential diagnosis, morphology and associations of de-POFLs are
      also listed and some of the associated genetic conditions are reviewed. SUMMARY:
      Familiarity with the morphologic and ophthalmoscopic features of pigmented and de
      POFLs is essential for the ophthalmologist so that an exact diagnosis is made and
      the appropriate workup and referrals initiated.

PMID- 22847031
TI  - Visual processing and learning disorders.
AB  - PURPOSE OF REVIEW: Many children are seen by ophthalmologists because of
      scholastic difficulties in school initially attributed to eyesight when, in fact,
      the problem often is a result of a disorder of the brain processing vision. A
      number of neuropsychological conditions predisposing and affecting children with
      learning disorders will be described. Visual processing is the main brain
      function allowing normal perception of what is being viewed. Ophthalmologists as
      well as patients must realize that with normal 20/20 eyesight interpretation of
      what is seen may be dysfunctional because of faulty brain processing of that
      which is seen by normal eyes. Abnormal Visual Processing as well as auditory
      processing disorders eventually lead directly to learning disorders in children
      and young adults. RECENT FINDINGS: New Clinical Practice Guidelines for the
      diagnosis, evaluation and treatment of children with attention deficit disorder
      (ADD)/attention deficit hyperactive disorder (ADHD) have been established by the
      American Academy of Pediatrics. An overgrowth of neurons in the prefrontal cortex
      of children with autism has recently been discovered. Six out of 1000 children
      have been reported as having Pervasive Developmental Disorder (PDD), which is
      another name for Autism Spectrum Disorder (ASD). A number of alternative
      treatments for ASD have recently been published. The families of autistic
      children have increased emotional and financial burdens, often affecting the
      workplace. SUMMARY: Recent neuropsychology discoveries have helped in the
      prevention, evaluation and treatment of children with visual processing and
      learning disorders. Quality-of-life and educational efficiency therefore can be
      improved.

PMID- 22847030
TI  - eyeGENE(R):  a novel approach to combine clinical testing and researching genetic
      ocular disease.
AB  - PURPOSE OF REVIEW: Molecular genetics is revolutionizing the diagnosis and
      treatment of inherited eye diseases. The National Eye Institute of the National
      Institutes of Health (NIH), in an effort to facilitate future basic and clinical
      research in inherited eye disease, created The National Ophthalmic Disease
      Genotyping and Phenotyping Network (eyeGENE). This review describes the process
      and utility of the eyeGENE program as it relates to ophthalmic clinical practice.
      RECENT FINDINGS: Over the last few years, genetic testing of specific genes
      associated with inherited eye conditions is becoming the standard practice.
      Vision research and human clinical trials relying on molecular genetic testing of
      individuals with inherited eye conditions are becoming more common. Eye
      healthcare professionals must consider the options to assist patients in
      obtaining genetic testing results and locating trials or studies that may have
      benefit. SUMMARY: eyeGENE is a DNA repository and patient registry for inherited
      eye diseases coupled to phenotypic descriptors and molecular genetic information.
      Through eyeGENE, healthcare professionals throughout the United States and Canada
      can obtain Clinical Laboratory Improvement Amendments-certified clinical
      molecular genetic results on their patients. Researchers may request access to a
      de-identified database of phenotype and genotype information about eyeGENE
      participants and DNA aliquots for their research studies. eyeGENE also offers
      participants the option of being included in a patient registry, whereby they may
      be re-contacted if an approved clinical study for which they might qualify is
      offered.

PMID- 22847032
TI  - Prosthetic joint infections.
AB  - Prosthetic joint infections represent a major therapeutic challenge for both
      healthcare providers and patients. This article reviews the predisposing factors,
      pathogenesis, microbiology, diagnosis, treatment, and prophylaxis of prosthetic
      joint infection. The most optimal management strategy should be identified on the
      basis of a number of considerations, including type and duration of infection,
      antimicrobial susceptibility of the infecting pathogen, condition of infected
      tissues and bone stock, patient wishes, and functional status.

PMID- 22847035
TI  - Microcystic adnexal carcinoma of the upper lip misdiagnosed benign desmoplastic
      trichoepithelioma.
AB  - BACKGROUND: Desmoplastic trichoepithelioma (DT) is a benign appendageal tumour
      predominately localized on the facial skin. The histological diagnosis can be
      difficult in some cases. Partial malignant transformation of a DT is a rarity and
      a complete transformation has never been described in literature. CASE REPORT: A
      DT of the upper lip was diagnosed histologically by a small biopsy 4 years
      previously. At presentation, the tumour had enlarged and had partly infiltrated
      the left side of the upper lip and subnasal region. Histological evaluation
      confirmed a microcystic adnexal carcinoma but without evidence of malignant
      transformation of the DT. It appeared that a too-small initial biopsy had led to
      the incorrect histological diagnosis of a benign tumour. Thus, it was necessary
      to perform a tumour resection and reconstruction using a two-flap technique
      including a rotation flap and an Abbe flap. Functional and aesthetic outcomes
      were good after 6 months. There were no recurrences during a 12-month follow-up.
      CONCLUSION: A facial DT should be resected completely. Patients should be
      attended for follow-ups, keeping in mind the difficulty of making a proper
      histological diagnosis from small biopsies or excisions and the consequences of
      ablative facial surgery. However, in particular cases, subtotal defects of the
      upper lip region are amenable to reconstruction without gross functional or
      aesthetic deficits.

PMID- 22847036
TI  - Paranasal sinus infection causing orbital subperiosteal abscess: surgical
      management of this devastating entity.
AB  - BACKGROUND: Orbital infection is an uncommon devastating infection and is usually
      a complication of paranasal sinus infection. Without appropriate treatment,
      orbital infection may lead to serious complications, even death. Prompt treatment
      is mandatory to avoid visual loss or intracranial complications. The literature
      shows that initially, intravenous antibiotics should be administered, and after
      48 h, if no improvement appears, the affected orbit and the sinuses must be
      surgically drained. The authors describe two cases of orbital cellulitis with a
      brief literature review. CASE REPORT: The authors describe two cases of orbital
      abscess caused by paranasal sinus infection. In case 1, the patient presented a
      decreased visual acuity associated with ophthalmoplegia of the right eye. In case
      2, the patient presented a decreased visual acuity. Thus, administration of
      intravenous antibiotic combined with surgical drainage was performed. After
      surgical procedure, eye movements were normalized in case 1, and in both
      patients, the visual acuity returned to normal parameters. DISCUSSION: The
      authors recommend early surgical drainage with parenteral antibiotic
      administration and careful postoperative observations by monitoring the signs and
      symptoms of the orbital complaint.

PMID- 22847033
TI  - Septic arthritis in the native joint.
AB  - Septic arthritis of the native joint is an uncommon infection but, when present,
      creates a significant risk for functional impairment of the affected joint or, in
      severe cases, mortality. Knowledge of the most common pathogens, as well as
      appropriate diagnostics, can facilitate earlier diagnosis and treatment, which,
      ideally, leads to improved long-term outcomes. In this article, we discuss recent
      microbiologic trends and diagnostic tests, with an update on use of molecular
      testing. Empiric antibiotic regimens for native joint septic arthritis are
      reviewed, as well as potential new therapies on the horizon.

PMID- 22847038
TI  - Ectopic mandibular third molar leading to osteomyelitis of condyle: a case report
      with literature review.
AB  - BACKGROUND: A tooth is said to be ectopic if it is malpositioned either due to
      congenital factors or displaced due to pathological lesions. The incidence of
      osteomyelitis of condyle has a rare occurrence, very few cases have been
      reported, either their etiology is unknown or is due to hematogenous spread or a
      tuberculous focus. This particular case may be a rare of its kind, as recent
      literature did not reveal any case where an ectopic mandibular third molar led to
      osteomyelitis of the condyle. CASE REPORT: This report presents a unique case
      where an ectopically placed mandibular third molar led to extraoral sinus and
      scar formation below the ear lobule with osteomyelitis of the mandibular condyle
      and proposes various indications for its removal along with literature review.
      DISCUSSION: Ectopic eruption of a tooth into the dental environment is common,
      whereas ectopic eruption of tooth in other sites is rare. The exact etiology of
      ectopic eruption of mandibular third molar in condyle is a rare occurrence and to
      the best of our knowledge, only 14 cases have been reported in the literature.
      Management of such cases should be meticulously planned after ruling out various
      local as well as systemic factors as an underlying cause for osteomyelitis and on
      the basis of the position and type of ectopic tooth and related potential trauma
      which could be caused by surgical intervention with less morbidity. CONCLUSION:
      This particular case may be the unique of its kind, as recent literature did not
      reveal any case where an ectopic mandibular third molar led to osteomyelitis of
      the condyle. Diagnosis and management in such cases deserve very special
      attention to rule out various local and systemic causes which can cause
      osteomyelitis to affect very unusual site like mandibular condyle. The aim of
      surgical intervention should be to cause minimum morbidity without affecting the
      functional efficiency of the mandibular condyle. In this report, we also have
      proposed the indications for surgical intervention to remove ectopically erupted
      teeth.

PMID- 22847039
TI  - Parotid surgery for benign tumours.
AB  - PURPOSE: The majority of parotid tumours are benign, making parotid surgery a
      compromise between adequate tumour excision and preservation of function and
      facial harmony. Besides the traditional superficial or total parotidectomy, less
      invasive techniques have been described with similar recurrent rates. The aim of
      this review is to assess the evidence in the published literature and to
      summarise the advantages and disadvantages of the available techniques. METHODS:
      A systematic search in Pubmed for studies on surgery of benign parotid tumours
      (BPTs) published between January 2000 and January 2012 was conducted. Case series
      with a clear description of the surgical technique and a minimum number of 10
      patients were included. RESULTS: Four hundred sixty-three articles were found, 49
      abstracts reviewed and 37 case series were selected for this review. The surgical
      techniques for benign parotid tumours can largely be grouped into facial nerve
      dissecting (superficial parotidectomy, partial superficial parotidectomy and
      total parotidectomy) and non-nerve dissecting techniques (extracapsular
      dissection). With all of the currently used techniques, a low recurrence (<3 %)
      with a low incidence of permanent facial nerve morbidity (0.2-4 %) can be
      achieved. The tumour-facial nerve interface and pseudopodia are areas at risk for
      positive margins. CONCLUSION: There is currently no agreement in the literature
      about the extent of surgery for BPTs to obtain an adequate margin. The tumour
      nerve interface is the predetermined area at risk for tumour spillage and
      positive margin. A prolonged follow-up is recommended. Further long-term
      randomised clinical trials are required to address the question of the extent of
      the excision in benign parotid surgery.

PMID- 22847040
TI  - Histologic assessment of tumor-associated CD45(+) cell numbers is an independent
      predictor of prognosis in small cell lung cancer.
AB  - BACKGROUND: Small cell lung carcinoma (SCLC) continues to have a poor prognosis,
      with a 2-year survival of < 20%. Studies have suggested that SCLC may affect the
      immune system to allow it to evade immunologic responses. We hypothesized that
      any such effect would be characterized by a decrease in the lymphoid cells
      associated with the tumor in biopsy specimens and that this might relate to
      patient outcome. METHODS: Sixty-four SCLC biopsy specimens were
      immunohistochemically stained with anti-CD45 antibody to identify immune cells
      associated with the tumor. A mean CD45 count per high-power field for each case
      was obtained, and the results were correlated with age, sex, stage, performance
      status (PS), treatment with chemotherapy/radiotherapy, and overall survival.
      RESULTS: The median CD45 count for all cases was taken as 40 (CD45(40)). Kaplan
      Meier plots demonstrated better survival for patients with a CD45(40) > 40 ( P <
      .009). No relationship between CD45 40 and age, sex, stage, or treatment by
      chemotherapy or radiotherapy was identified. Although PS was a significant
      predictor of survival ( P = .014), it did not correlate with CD45 40. In patients
      with better Eastern Cooperative Oncology Group PS (<= 2), the CD45(40)
      demonstrated a highly significant survival advantage for those with CD45(40) > 40
      ( P < .0001). CONCLUSIONS: The data indicate that (1) simple immunohistochemical
      assessment of immune cell infiltrates in routinely processed and stained biopsy
      specimens of primary tumors can provide prognostic information in SCLC and (2)
      tumor-associated CD45(+) cells in SCLC biopsy specimens may be a good clinical
      marker to identify patients with poor prognosis despite good PS.

PMID- 22847042
TI  - Efficacy and timing of intra-aortic counterpulsation in patients with ST
      elevation myocardial infarction complicated by cardiogenic shock.
AB  - BACKGROUND: Guidelines strongly recommend additional intra-aortic balloon pump
      (IABP) therapy in STEMI patients with cardiogenic shock (CS) treated by primary
      percutaneous coronary intervention (PCI). However, there is no randomised
      evidence suggesting survival benefit of IABP treatment in CS. It is suggested
      that timing of initiation of IABP therapy could be of great importance.
      Therefore, we compared mortality rates of IABP therapy versus no IABP therapy in
      the setting of STEMI complicated by CS. In addition, we investigated the effect
      of initiation of IABP therapy on mortality. METHODS: From a cohort of 292 STEMI
      patients with CS treated by primary PCI, 199 patients received IABP therapy (IABP
      group) and 93 patients received no support (no IABP group). The IABP group was
      divided into two subgroups based on timing of initiation of support, i.e. 'IABP
      pre PCI' (n = 59) and 'IABP post PCI' (n = 140). Outcomes were assessed by
      propensity stratification and multivariate logistic regression. RESULTS: All
      cause 30-day mortality for the IABP versus the no IABP group was 47 % vs. 28 %,
      respectively, in univariate analysis resulting in an odds ratio (OR) of 1.67
      (95%CI, 1.16 to 2.39). However, analyses adjusting outcomes by propensity
      stratification and logistic regression, respectively, neutralised this OR. In the
      IABP pre-PCI group vs. the post-PCI group 30-day mortality was 64 % vs. 40 %,
      resulting in an OR of 1.56 (95 % CI, 1.18 to 2.08). However, after propensity
      stratification analysis and multivariate logistic regression analysis, there were
      no significant differences in odds of 30-day mortality. CONCLUSION: In our cohort
      of patients with STEMI complicated by CS treated with primary PCI we observed a
      difference in mortality between those treated with IABP and those treated without
      IABP in favour of the 'no IABP' group. The mortality difference was eliminated
      after adjustment for differences in case mix by propensity stratification or by
      logistic regression analysis. Neither did we observe any difference in mortality
      between patients whose IABP treatment was initiated before or immediately after
      PCI.

PMID- 22847037
TI  - Unusual intramaxillary plexiform schwannoma.
AB  - BACKGROUND: Neoplasms of peripheral nerve in the head and neck region are of
      common occurrence, but origin in the oral and para-oral tissues is uncommon and
      they rarely occur centrally within the jaws. Schwannoma is a benign neoplasm
      originating from the neural sheath of peripheral soft tissues, but its occurrence
      within the jaw bones is most unusual. Plexiform schwannoma is a unique variant of
      Schwann cell tumours having plexiform pattern. Literature revealed only one case
      of plexiform schwannoma of the jaw bones, i.e. involving the mandible. CASE
      REPORT: In this report, we present the first documented case of intraosseous
      plexiform schwannoma of the maxilla, an extremely rare benign neurogenic tumour
      treated surgically. DISCUSSION: Schwannoma is a benign neoplasm originating from
      the neural sheath of peripheral soft tissues, but to occur within the jaw bones
      is exceptional. Plexiform schwannoma is a rare variant of Schwann cell tumour
      having plexiform pattern of intraneural growth with multinodularity. Plexiform
      schwannoma is a benign neoplasm with no malignant potential, but recurrences are
      evident if excised incompletely. Plexiform schwannoma has similar clinical and
      histopathological features as that of plexiform neurofibroma which has high
      malignant potential; hence, it is imperative to correctly diagnose and
      differentiate this lesion as treatment modality of these two lesions differs.

PMID- 22847041
TI  - Is cardiac CT a reproducible alternative for cardiac MR in adult patients with a
      systemic right ventricle?
AB  - OBJECTIVE: 20 % of patients with a systemic RV are pacemaker dependent, and
      unsuitable to undergo cardiac magnetic resonance (CMR). Multidetector row
      computed tomography (MDCT) could provide a reproducible alternative to CMR in
      these patients. The aim of this study was to compare variability of MDCT with
      CMR. METHODS: Thirty-five patients with systemic RV underwent either MDCT (n =
      15) or CMR (n = 20). Systemic RV volumes and ejection fraction were obtained, and
      intra- and interobserver variability for both modalities were assessed and
      compared. RESULTS: We found the intra- and interobserver variability of volumes
      and function measurements of the systemic RV obtained with MDCT to be higher
      compared with those obtained with CMR. However, these differences in variability
      were not significant, the only exception being the interobserver variability of
      systemic RV stroke volume. CONCLUSIONS: MDCT provides a reproducible alternative
      to CMR for volumes and function assessment in patients with a systemic RV.

PMID- 22847043
TI  - Noncompaction cardiomyopathy, a frequently overlooked entity (...but beware of
      over diagnosis!).

PMID- 22847044
TI  - Seeing through the eyes of patients: the Patient-Centered Outcomes Research
      Institute Funding Announcements.

PMID- 22847045
TI  - The relationship of victim injury to the progression of sexual crimes through the
      criminal justice system.
AB  - A number of factors are known to influence the progression of sexual crimes
      through the criminal justice system. The role of victim injury in influencing
      decision-making at pivotal stages has been addressed by a number of separate
      research projects. This article consolidates existing research evidence in order
      to highlight the important role that victim injury plays at each step of the
      legal process. The importance of accurate diagnosis and recording of victim
      injury is highlighted. Furthermore, by describing the significant impact that the
      presence of victim injury can have on the legal outcome, the importance of
      ensuring that cases without victim injury are correctly interpreted by the
      police, legal professionals, judiciary and the jury is heavily emphasised.

PMID- 22847046
TI  - Marantic endocarditis - A not so benign entity.
AB  - Marantic, verrucous or nonbacterial thrombotic endocarditis, is characterised by
      the deposition of an amorphous mixture of fibrin and platelets onto heart valves.
      Although not commonly a cause of death in forensic practice, it may be associated
      with systemic embolisation. This was observed in a 60-year-old woman who suddenly
      collapsed and was found at autopsy to have a poorly differentiated adenocarcinoma
      of the lung with vegetations from marantic endocarditis on the mitral valve and
      embolisation with infarcts in the left kidney, the spleen, the right occipital
      cortex of the brain and the left ventricle of the heart. Death was due to
      coronary artery embolism from marantic endocarditis associated with an
      undiagnosed adenocarcinoma of the lung. Although marantic endocarditis is more
      common in hospital autopsies than in forensic cases, it can have lethal
      complications that result in sudden and unexpected death. Histories of
      debilitating disease and/or arterial thromboembolic episodes necessitate
      meticulous examination of the cardiac valves with careful serial sectioning of
      the major epicardial coronary arteries and histologic sampling of both
      ventricles.

PMID- 22847047
TI  - Estimation of length of humerus from its fragmentary portions.
AB  - The objective of the present study was to estimate the length of humeri from
      measurements of their fragments in south Indian population. This is important in
      forensic investigations and in archaeological studies particularly when the
      fragmentary portions are examined. For this purpose 200 adult humeri, 100 each of
      either sex in dried and fully ossified condition were taken for study. Each of
      the humerus bone was fragmented into five fragments by drawing imaginary lines
      with reference to their specific anatomical landmarks. The fragments are H2 (a
      b), H3 (b-c), H4 (c-d), H5 (d-e) and H6 (e-f). After applying necessary
      statistical analysis a definite mathematical correlation in forms of proportion
      and regression equation was established between each fragment to the total length
      of humerus (H1). All the formulae thus derived for each of the fragments of bones
      are not only significant but also possess a high degree of prediction. Among all
      the fragments, the longest fragmentary portion i.e.H4 (c-d) predicts the highest
      percentage of accuracy (H1=166+0.712 H4 M, H1=90.2+1.06 H4F) followed by H2 (a-b)
      in calculating the total length of humerus (H1=307+0.330 H2M, H1=243+1.73 H2F).
      In conclusion, our study demonstrated that length of the humerus can be estimated
      from measures of different fragments.

PMID- 22847048
TI  - Mortality among homeless and unclaimed bodies in Mangalore city - An insight.
AB  - Homelessness is a social as well as legal stigma on a Country's development
      index. In addition homeless people are exposed to increased incidence of diseases
      and accidents. Mangalore city, a bustling city located in Southern costal region
      of India, has seen tremendous growth in the past few years; with this the problem
      of migrants and homeless has also increased. This has invited a spectrum of
      problems relating to law and order including frequent incidences of unclaimed
      dead bodies, both due to natural and unnatural causes. This autopsy based study
      tries to highlight the situation of picture of homeless deaths in Mangalore and
      the problems faced by the Law enforcing authorities.

PMID- 22847049
TI  - Health-care issues and health-care use among detainees in police custody.
AB  - Epidemiological research on the physical health status of police detainees is
      scarce. The present study fills this gap by first studying the somatic reasons
      for consultation (n = 4396) and related prescriptions (n = 4912) as assessed by
      the forensic medical service during police detainment. Secondly, a health
      interview survey was conducted among randomly selected police detainees (n = 264)
      to collect information regarding their recent disease history and use of health
      care. Somatic health problems, medical consumption and health risk measures of
      the detainees were compared with those seen in the general population using
      general practitioner records and community health survey data. The study showed
      that, in police detainment, several chronic health conditions more often were the
      reason for consultation than in the general practice setting. In addition, the
      health interview survey data demonstrated that after adjustment for age and
      gender, the police detainees were 1.6 times more likely to suffer from one or
      more of the studied chronic diseases than the members from the general
      population. Furthermore, differences in several health risk measures, including
      body mass index, smoking and alcohol habits and health-care use were observed
      between the interviewed police detainees and the general population. These
      results provide insight into the variety of physical health problems of police
      detainees and are essential to develop optimal treatment strategies in police
      custody.

PMID- 22847050
TI  - Mental health of young offenders in Switzerland: Recognizing psychiatric symptoms
      during detention.
AB  - We reviewed the medical records of the 118 adolescent detainees which had at
      least one consultation by a psychiatrist at the prison health facility during
      2007. General practitioners used the International Classification of Primary Care
      (ICPC-2) for recording health problems. Psychiatrists used the International
      Classification of Diseases (ICD-10) for making psychiatric diagnoses. The
      concordance between the mental health assessment done by general practitioners
      using the ICPC-2 and the diagnoses proposed by psychiatrists was globally
      satisfying. The five most frequent ICD categories (conduct disorder, drug abuse,
      alcohol abuse, personality disorder, adjustment disorder) encompassed the most
      frequently reported ICPC-2 psychological symptoms. Several associations between
      psychological symptoms and socio-demographic characteristics were observed. Apart
      from providing a description of the mental health of adolescent detainees in one
      of Switzerland's largest detention centre for minors, results suggest that
      general practitioners can adequately identify frequent mental disorders in such
      contexts.

PMID- 22847051
TI  - Exhumation - Nuisance to the dead, justified?
AB  - OBJECTIVE: Exhumation stands as a very significant feature of forensic
      investigations. The legal excavation of dead bodies for ascertainment of the
      cause of death has always aided the law enforcement agencies to comprehend the
      anonymity of any suspicious case and further convict the criminal in cases of
      homicides. This study analyses the different aspects of the exhumations which
      were carried out and were autopsied in Karachi during the study period. METHOD:
      This was a cross-sectional study, and included all the exhumations carried out in
      Karachi during a period of 7 years and 7 months from 1 January 2004 to 31 July
      2011. RESULTS: A total of 101 exhumations were carried out during the study
      period. Out of 101 cases, 63 were males (62.4%) and 38 females (37.6%) giving a
      male to female ratio of about 3:2. Causes of death were ascertained in 75 cases,
      thus the success rate was 74.3%. Head injury by hitting with hard blunt object
      was the most frequent cause of deaths (17.8%), followed by asphyxia due to
      strangulation (15.8%). DISCUSSION: Exhumations must be ordered by the Judiciary
      in suspicious cases as it aids in determining the actual causes of death and
      leads to convictions. It also brings a great deal of satisfaction for the
      relatives of the deceased and halts any doubts in their minds. As shown by our
      study, much attention is given to the cases in urban areas by the relatives who
      are determined to find the cause of death even after burial procedures.

PMID- 22847052
TI  - When nightclub security agents assault clients.
AB  - In 2006, a medico-legal consultation service devoted to adult victims of
      interpersonal violence was set up at the Lausanne University Hospital Centre,
      Switzerland: the Violence Medical Unit. Most patients are referred to the
      consultation by the Emergency Department. They are received by forensic nurses
      for support, forensic examination (in order to establish medical report) and
      community orientation. Between 2007 and 2009, among community violence,
      aggressions by security agents of nightclubs on clients have increased from 6% to
      10%. Most of the victims are young men who had drunk alcohol before the assault.
      25.7% presented one or several fractures, all of them in the head area. These
      findings raise questions about the ability of security agents of nightclubs to
      deal adequately with obviously risky situations and ensure client security.

PMID- 22847053
TI  - Membership survey of the Australasian College of Legal Medicine: Quality
      assurance.
AB  - INTRODUCTION: The Council of the Australasian College of Legal Medicine (ACLM)
      considered it timely to survey its membership to determine how to best
      accommodate its members' needs. METHODS: A questionnaire was devised, piloted and
      circulated amongst the 219 College members (excluding the 13 Honorary Fellows).
      Yield was maximised with 4 direct mailings, 4 questionnaire insertions in the
      quarterly College newsletter, 3 targeted emails and follow-up phone calls.
      RESULTS: The survey achieved 160 (73%) response rate of whom ~40% were
      substantially involved in legal and forensic medicine and ~40% were occasionally
      involved. Thirty-five participants (23%) specialised in forensic medicine and 101
      (63%) held Fellowship status in other recognised medical specialities. Equal 1/3
      of the members had been so for >10 years, 5-10 years or <5 years, demonstrating
      the dynamic nature of the College. Of them 53% were Fellows, 26% Members and 21%
      Associates with 50% of the latter groups willing to train towards Fellowship.
      About half the respondents (48%) regularly attended the Annual Scientific Meeting
      (ASM) and favoured the Eastern border for such meetings. The collegiate nature of
      the College was deemed its most positive aspect with a dichotomy of views
      regarding seeking alternative strand affiliation for specialist recognition,
      although 80% indicated they would retain College membership even if such
      affiliation occurred. Those who attended College educative programs found them
      useful but attendance was between 32 and 49%, depending on the course.
      DISCUSSION: There appeared widespread satisfaction with College performance and
      activities but a low uptake of educative courses, other than Annual Scientific
      Meetings, thereby identifying marketing of courses as needing extra attention.

PMID- 22847054
TI  - Penetrating cardiac injuries in blunt chest wall trauma.
AB  - The present photocase illustrates the possible mechanism of direct cardiac
      injuries from broken sharp jagged fractured ends of ribs in blunt force trauma to
      the chest in run over traffic mishaps. We propose that the projecting fractured
      ends of the ribs penetrate the underlying thoracic organs due to the transient
      phenomenon of deformation of chest cavity under pressure in run over traffic
      mishaps.

PMID- 22847055
TI  - Harlequin ichthyosis: A medico legal case report & review of literature with
      peculiar findings in autopsy.
AB  - Ichthyosis fetalis or Harlequin ichthyosis is an extremely severe and fatal
      hereditary skin disorder with an autosomal recessive inheritance. It is
      distinctive because of its remarkable clinical appearance which includes
      epidermal keratinization, hypoplasia of fingers or nails, malformation of ear and
      nose and incompatibility with life. This report describes a case of Harlequin
      ichthyosis along with detailed autopsy findings, which manifested the suspended
      animation in the early hours after delivery and showing a peculiar malformation
      of the cerebral hemispheres. To the best of the knowledge, this may be the first
      report of Harlequin ichthyosis in the forensic literature describing mal
      development of cerebral hemispheres and suspended animation in a case of
      Harlequin Ichthyosis.

PMID- 22847056
TI  - A case of self amputation of penis by cannabis induced psychosis.
AB  - Self-mutilation, self-injuring or self-harming behaviour has been defined as
      deliberate destruction or alteration of body tissue in the absence of conscious
      suicidal intention. Persons suffering from mental disorder may inflict hundred of
      small wounds upon themselves which may be added to the actual cause of death.
      Another recognized syndrome is self mutilation of genitals almost invariably in
      males suffering from paranoid schizophrenia and often with strong religious
      flavour to their delusion. Here we present a case of a 35-year-old male who self
      mutilated his penis due to dependence on cannabis for the past few years that led
      to a condition called cannabis induced psychosis.

PMID- 22847057
TI  - Fatal and non-fatal cases of lime sulfide exposure and pathogenetic mechanisms
      underlying pancreatic injury: Case reports with an animal experiment.
AB  - Lime sulfide poisoning by the oral route is rarely encountered in the practice of
      forensic science, whereas hydrogen sulfide poisoning is seen frequently. We
      report here two cases of fatal lime sulfide poisoning with several related cases
      and in addition induced histological damage with acute inflammation in animal
      models under at similar concentrations. We also evaluated sulfide and thiosulfate
      concentrations and speculated as to the cause of pancreatic damage in these
      cases.

PMID- 22847058
TI  - Can mild organophosphate poisoning result in myocardial infarction?

PMID- 22847059
TI  - Effect of rosiglitazone on capillary density and angiogenesis in adipose tissue
      of normoglycaemic humans in a randomised controlled trial.
AB  - AIMS/HYPOTHESIS: Recent reports of decreased capillary density in the adipose
      tissue of obese individuals suggest that an imbalance of angiogenesis and
      adipogenesis may, in part, underlie insulin resistance. This study aimed to
      determine whether the insulin-sensitising peroxisome proliferator-activated
      receptor gamma (PPARgamma) activator rosiglitazone affects adipose tissue
      vascularisation in normal humans. METHODS: A randomised, parallel-group,
      investigator-blinded placebo-controlled trial was conducted with normoglycaemic
      volunteers with BMI 27-43, recruited from the community at the University of
      Massachusetts Medical School, Worcester, MA, USA. Peri-umbilical adipose tissue
      biopsies were obtained before and after treatment for 6 weeks with rosiglitazone
      (8 mg once daily) or placebo, which were randomly allocated from a sequentially
      numbered list. The primary outcomes were adipocyte size and capillary density
      measured by immunohistochemistry, and angiogenic potential assessed by capillary
      sprout formation in Matrigel. Secondary outcomes were serum adiponectin,
      glycaemic, lipid and liver function variables. RESULTS: A total of 35 individuals
      fulfilling the inclusion criteria were randomised, and complete before-vs-after
      analyses were achieved in 30 participants (13 and 17, placebo and rosiglitazone,
      respectively). Significant differences, assessed by paired two-tailed Student t
      tests, were seen in response to rosiglitazone for adipocyte size (3,458 +/- 202
      vs 2,693 +/- 223 MUm(2), p = 0.0049), capillary density (5.6 +/- 0.5 vs 7.5 +/-
      0.5 lumens/field, p = 0.0098), serum adiponectin (14.3 +/- 1.5 vs 28.6 +/- 3.0
      ng/ml, p < 0.0001) and alkaline phosphatase (1.04 +/- 0.07 vs 0.87 +/- 0.05
      MUkat/l, p = 0.001). A difference in angiogenic potential before and after
      treatment between the placebo and rosiglitazone groups was also seen (-23.88 +/-
      14 vs 13.42 +/- 13, p = 0.029, two-tailed Mann-Whitney test).
      CONCLUSIONS/INTERPRETATION: Significant effects on adipose tissue vascular
      architecture occur after a short period of treatment with rosiglitazone in
      individuals with normal glucose tolerance. Improved adipose tissue
      vascularisation may, in part, mediate the therapeutic actions of this class of
      drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01150981 FUNDING: The study was
      funded by National Institutes of Health grant DK089101 to S. Corvera, and by
      pilot funding from the University of Massachusetts (UMASS) Center for Clinical
      Translational Sciences (M. Thompson, S. Malkani and S. Corvera). Morphology core
      services were supported by UMASS Diabetes Endocrine Research Center (DERC) grant
      DK32520.

PMID- 22847061
TI  - Beta cell nuclear musculoaponeurotic fibrosarcoma oncogene family A (MafA) is
      deficient in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The beta cell transcriptional factor musculoaponeurotic
      fibrosarcoma oncogene family A (MafA) regulates genes important for beta cell
      function. Loss of nuclear MafA has been implicated in beta cell dysfunction in
      animal models of type 2 diabetes. We sought to establish if nuclear MafA is less
      abundant in beta cell nuclei in humans with type 2 diabetes. METHODS: Pancreas
      obtained at surgery from five non-diabetic individuals and six individuals with
      type 2 diabetes was immunostained for insulin, glucagon and MafA. RESULTS: Beta
      cell nuclear MafA was markedly decreased in type 2 diabetes (1.6 +/- 1.2% vs 46.3
      +/- 8.3%, p < 0.001). CONCLUSIONS/INTERPRETATION: Beta cell nuclear MafA is
      markedly decreased in humans with type 2 diabetes, which may contribute to
      impaired beta cell dysfunction.

PMID- 22847060
TI  - Elevated NEFA levels impair glucose effectiveness by increasing net hepatic
      glycogenolysis.
AB  - AIMS/HYPOTHESIS: Acute hyperglycaemia rapidly suppresses endogenous glucose
      production (EGP) in non-diabetic individuals, mainly by inhibiting
      glycogenolysis. Loss of this 'glucose effectiveness' contributes to fasting
      hyperglycaemia in type 2 diabetes. Elevated NEFA levels characteristic of type 2
      diabetes impair glucose effectiveness, although the mechanism is not fully
      understood. Therefore we examined the impact of increasing NEFA levels on the
      ability of hyperglycaemia to regulate pathways of EGP. METHODS: We performed 4 h
      'pancreatic clamp' studies (somatostatin; basal glucagon/growth hormone/insulin)
      in seven non-diabetic individuals. Glucose fluxes (D-[6,6-(2)H(2)]glucose) and
      hepatic glycogen concentrations ((13)C magnetic resonance spectroscopy) were
      quantified under three conditions: euglycaemia, hyperglycaemia and hyperglycaemia
      with elevated NEFA (HY-NEFA). RESULTS: EGP was suppressed by hyperglycaemia, but
      not by HY-NEFA. Hepatic glycogen concentration decreased ~14% with prolonged
      fasting during euglycaemia and increased by ~12% with hyperglycaemia. In
      contrast, raising NEFA levels in HY-NEFA caused a substantial ~23% reduction in
      hepatic glycogen concentration. Moreover, rates of gluconeogenesis were decreased
      with hyperglycaemia, but increased with HY-NEFA. CONCLUSIONS/INTERPRETATION:
      Increased NEFA appear to profoundly blunt the ability of hyperglycaemia to
      inhibit net glycogenolysis under basal hormonal conditions.

PMID- 22847063
TI  - Diagnosis and management of behavioral issues in frontotemporal dementia.
AB  - Frontotemporal lobar degeneration is an umbrella term for several different
      disorders. In behavioral variant frontotemporal dementia (bvFTD), patients show
      deterioration in cognition and social behavior. New diagnostic criteria proposed
      by the International Behavioral Variant FTD Consortium provide greater
      sensitivity in diagnosing bvFTD. Current pharmacological management of symptoms
      relies on medications borrowed from treating Alzheimer's disease (AD) and
      psychiatric disorders. The evidence for using AD medications such as
      acetylcholinesterase inhibitors is questionable. Psychiatric medications can be
      helpful. Trazodone or SSRIs can have some efficacy in reducing disinhibition,
      repetitive behaviors, sexually inappropriate behaviors, and hyperorality. Small
      doses of atypical antipsychotics may be helpful in decreasing agitation and
      verbal outbursts. Nonpharmacological management includes caregiver education and
      support and behavioral interventions. While symptomatic treatments are likely to
      remain important behavior management tools, targeting the underlying pathology of
      bvFTD with disease-modifying agents will hopefully be the future of treatment.

PMID- 22847064
TI  - Microglial LOX-1 reacts with extracellular HSP60 to bridge neuroinflammation and
      neurotoxicity.
AB  - Chronic neurodegeneration is in part caused by a vicious cycle of persistent
      microglial activation and progressive neuronal cell loss. However, the driving
      force behind this cycle remains poorly understood. In this study, we used medium
      conditioned by necrotic differentiated-PC12 cells to confirm that damaged neurons
      can release soluble injury signals, including heat shock protein 60 (HSP60), to
      efficiently promote the neurotoxic cycle involving microglia. Since lectin-like
      oxidized low-density lipoprotein receptor-1 (LOX-1) has previously been
      identified as a novel receptor for HSP60, we hypothesize that LOX-1 through
      binding to extracellular HSP60 promotes microglia-mediated neuroinflammation. In
      this study, we observed that LOX-1 expression is induced upon toxic microglial
      activation, and discovered that LOX-1 is necessary in microglia for sensing
      soluble neuronal injury signal(s) in the conditioned medium to induce generation
      of pro-inflammatory mediators (IL-1beta, TNF-alpha, NO and ROS) that promote
      neurotoxicity. Employing a unique eukaryotic HSP60-overexpression method, we
      further demonstrated that extracellular HSP60 acts on microglial LOX-1 to boost
      the production of pro-inflammatory factors (IL-1beta, NO and ROS) in microglia
      and to propagate neuronal damage. These results indicate that LOX-1 is essential
      in microglia for promoting an inflammatory response in the presence of soluble
      neuronal-injury signals such as extracellular HSP60, thereby linking
      neuroinflammation and neurotoxicity.

PMID- 22847065
TI  - Endovascular treatment of bilateral multiple carotid-cavernous fistulas in a
      patient with Ehlers-Danlos syndrome.
AB  - INTRODUCTION: In this article, we report the first patient with Ehlers-Danlos
      syndrome type IV (EDS IV) who developed multiple spontaneous contralateral direct
      carotid-cavernous fistulas (CCFs) after permanent occlusion of left internal
      carotid artery CCF 2 years before. We occluded the multiple fistulas and
      preserved the internal carotid artery (ICA) by using transarterial balloon
      assisted embolization with coils and Onyx. CASE REPORT: A 39-year-old woman
      presented with severe sudden-onset periorbital pain, increasing swelling, and
      proptosis of her left eye. Digital subtraction angiography (DSA) demonstrated
      direct left CCF. This patient underwent successful occlusion of left ICA and CCF
      by using detachable balloons. Two years later, she complained of a pulsatile
      intracranial bruit and then swelling and proptosis of her right eye.
      INTERVENTION: The right carotid artery angiogram revealed direct high-flow CCF
      with two fistulas in the cavernous segment of right ICA. Taking a transarterial
      approach, we occluded the two fistulas with GDC coils and Onyx-18 by an assisted
      balloon. CONCLUSION: In the management of multiple CCFs in EDS IV patients, we
      are able to occlude the fistulas and leave the ICA intact by using transarterial
      balloon-assisted embolization. Intensive follow-up of treated arteries is
      mandatory, because EDS IV is widespread and can occur on contralateral vessels as
      well.

PMID- 22847066
TI  - Giant suprasellar Rathke's cleft cyst mimicking craniopharyngioma: implications
      for a spectrum of cystic epithelial lesions of ectodermal origin.
AB  - Cystic epithelial lesions such as Rathke's cleft cysts (RCCs) and
      craniopharyngiomas may be difficult to distinguish on a clinical, radiographic,
      and sometimes histopathological basis. We describe a case of a giant 6.5 cm
      suprasellar cystic lesion that was presumed to be a craniopharyngioma based on
      the neuroimaging findings. The lesion extended from the anterior skull base and
      sella turcica to the lateral ventricle and sylvian fissure resulting in
      obstructive hydrocephalus. Complete surgical removal of the suprasellar lesion
      was achieved using an extended frontotemporal transbasal skull base approach.
      Intraoperatively, the cyst wall was thickened and partially calcified, resembling
      a craniopharyngioma. However, the histopathological examination revealed findings
      most consistent with a RCC with additional features of extensive squamous
      metaplasia, metaplastic bone formation, and chronic inflammation. The case raises
      the issue of whether there is a pathologic continuum of parasellar ectodermal
      lesions which may account for the overlap of features and transitional states. In
      this report, we discuss the possible spectrum between RCCs and
      craniopharyngiomas, and also emphasize the importance of complete resection of
      the cyst wall in RCCs that exhibit squamous metaplasia, inflammation, or
      ossification to minimize the probability of recurrence.

PMID- 22847067
TI  - Avoidance of electrode related MRI artifact during staged deep brain stimulator
      implantation.
AB  - BACKGROUND: Centers implanting deep brain stimulator (DBS) electrodes on
      different days often protect the first electrode tip with a protective cap,
      tunnel it under the scalp, and connect it to the generator at a later procedure.
      If magnetic resonance imaging (MRI) is used for planning during the second
      implantation, MRI artifacts from the protective cap could potentially corrupt the
      stereotactic coordinates. The importance of this problem may increase if emerging
      MRI safety data lead to more frequent use of MRI for these purposes. OBJECTIVE:
      To describe an MRI artifact arising from the use of the standard protective DBS
      cap that corrupts stereotactic planning and to describe a way to avoid the
      artifact. METHODS: After noting the artifact during a staged DBS procedure, a
      nonmetallic silastic sleeve contained in the existing DBS implantation kit was
      used in nine subsequent patients. Two caps with standard metallic screws were
      also tested with MRI phantoms. RESULTS: The silastic sleeve protected the DBS
      electrode but did not produce MRI artifact. The phantom studies demonstrated
      significant artifact from caps containing screws. CONCLUSION: A silastic sleeve
      provides adequate protection of the DBS electrode during staged implantation and
      avoids the MRI artifact associated with protective caps with screws.

PMID- 22847068
TI  - Visual loss from a pituitary mass: collision tumors of prostatic metastasis and
      suprasellar meningioma.
AB  - Central nervous system spread from prostate cancer is typically associated with
      raised prostate specific antigen (PSA) levels. The authors describe a unique case
      of a "collision tumor" of a prostatic metastasis to the pituitary, juxtaposed to
      a suprasellar meningioma, with normal PSA levels. This case also emphasizes the
      need to consider prostatic metastasis in the differential diagnosis of a
      pituitary mass in patients with a known prostatic cancer, despite the normal PSA
      levels. 

PMID- 22847069
TI  - New experimental model of terminal aneurysms in Swine: technical note.
AB  - BACKGROUND: Animal models of intracranial aneurysms are important for training
      surgeons and creating innovative endovascular treatment. Swine have physical
      dimensions close to those of humans and so are widely used in cardiology
      research. swine used as models for intracranial aneurysms have had difficulty
      maintaining long-term aneurysm patency. We present a swine model that may allow
      researchers to follow long-term outcomes after endovascular treatment. MATERIALS
      AND METHODS: We developed a terminal aneurysm model in swine (n = 3) using a vein
      pouch of an end-to-side anastomosis of the right carotid artery. We anastomosed
      the left carotid artery end and the right carotid artery side, designing it so
      the blood flows into the aneurysmal neck directly from the opposite side. we also
      anastomosed the ascending cervical artery and the right carotid artery, with flow
      reversal in the proximal right carotid artery by ligating the more proximal side.
      At the same time, a side-wall aneurysm was made, and we compared their patency
      periods. RESULTS: The terminal aneurysms remained patent for 3 months, and there
      were no major changes in their size or shape. In contrast, the side-wall
      aneurysms had become occluded at the 1-month follow-up. CONCLUSION: Our swine
      model displayed long-term patency and has the potential to allow long-term
      evaluation of new techniques and embolic agents.

PMID- 22847070
TI  - Successful endovascular treatment of carotid aneurysms in a patient with vascular
      Ehlers-Danlos syndrome.
AB  - BACKGROUND: Patients with vascular Ehlers-Danlos syndrome (EDS) can develop
      internal carotid artery (ICA) aneurysms. Any surgical procedure is hazardous and
      often unrewarding because of fragile blood vessels. Endovascular treatment may be
      an alternative approach to the treatment of ICA aneurysms in patients with
      vascular EDS. CASE: A 23-year-old woman with vascular EDS developed a cervical
      right ICA aneurysm and a left petrous ICA aneurysm, which were successfully
      treated with endovascular interventions without major complications. CONCLUSION:
      This case report suggests that endovascular treatment of ICA aneurysms is
      feasible and can be achieved in patients with vascular EDS.

PMID- 22847071
TI  - Understanding the failure of health-care exceptionalism in the Supreme Court's
      Obamacare decision.
AB  - On June 28, 2012, a mere century after the first presidential proposal for
      national health insurance, the Supreme Court issued a resounding victory for
      President Obama and for health-care reform generally, upholding the Patient
      Protection and Affordable Care Act against a serious constitutional challenge.
      Nevertheless, the Court also struck a potential blow to future health-care reform
      efforts in refusing to accept the solicitor general's argument that health care
      is a unique market with unique regulatory needs that justify special
      constitutional treatment. The failure of health-care exceptionalism in the
      Court's opinion might render future reform efforts more difficult than they would
      have been if the solicitor general's argument had carried the day. This
      commentary seeks to shed light on the Court's hesitation to recognize the
      uniqueness of health insurance and health care, noting that market-based
      exceptionalism in constitutional law has a long, dark history that the Court was
      understandably loath to repeat. Although the result of Chief Justice John
      Roberts' one-size-fits-all approach to constitutional analysis in this case is an
      odd holding that elides some genuine uniqueness of American health care, the
      alternative of health-care exceptionalism might have been much worse for our
      overall constitutional system.

PMID- 22847072
TI  - Manipulation of molecular rotational dynamics with multiple laser pulses.
AB  - In this paper, a theoretical model is proposed to investigate the molecular
      rotational state populations pumped by multiple laser pulses through an impulsive
      Raman process based on second-order perturbation theory and an analytical
      solution for the dependence of the rotational state populations on the time
      delays and the relative amplitudes of the multiple laser pulses has been
      achieved. The results indicate that the molecular rotational state populations
      can be controlled by precisely manipulating the time delays and the relative
      amplitudes, which can be significantly enhanced or completely suppressed, and so
      the molecular rotational wave packet and field-free molecular alignment can be
      efficiently manipulated.

PMID- 22847073
TI  - A novel and efficient colorimetric chemosensor for detection and determination of
      biologically important ions in DMSO/H2O media using bromo pyrogallol red
      chemosensors with analytical applications.
AB  - An efficient colorimetric chemosensor with bromo pyrogallol red (BPR) as an
      easily available dye demonstrated a high chromogenic selectivity for Fe(3+) over
      other cations with detection limit of 5.1 MUmol L(-1). The complex of Fe(3+) with
      BPR displayed ability to detect of up to 4.4 and 25.6 MUmol L(-1) for acetate
      (AcO(-)) and benzoate ions (BzO(-)) in DMSO/H(2)O (9:1 v/v) media respectively
      over a large number of other anions. Both processes proceeded with distinct
      visual color changes in DMSO/H(2)O (9:1 v/v). The linear dynamic ranges for the
      determinations of Fe(3+), AcO(-) and BzO(-) were 2.5-24.0, 2.5-20.5 and 28.0-42.0
      MUg mL(-1) respectively. This chemosensor was successfully applied for the
      determination of Fe(3+) and of carboxylate anions in environmental samples. This
      is the first article of a chemosensor capable of detecting both Fe(3+) and anions
      (AcO(-) and BzO(-)) using single detection method in a single cell.

PMID- 22847074
TI  - Nascent vessel elongation rate is inversely related to diameter in in vitro
      angiogenesis.
AB  - Recent angiogenesis studies have found nascent blood vessels to take on a wide
      diameter distribution (5-25 MUm) during the first 14 days of growth in murine
      explant models [Nunes S, et al., Microvascular Research, 2010, 79, 1-20], but the
      mechanisms determining diameter and its reported variability have not been
      explained. Here, we investigated the dominant mechanisms governing nascent vessel
      diameter by combining a 3D microfluidic angiogenesis model with a computational
      reaction-diffusion model. Cultured primary human endothelial cells sprouted from
      a monolayer into a 3D type I collagen matrix in the microfluidic model, and we
      found that vessel diameters were inversely correlated with their elongation
      rates. Several key species of matrix metalloproteinases (MMPs) are known to play
      important roles in matrix remodelling and vessel growth. We found that selective
      inhibition of soluble MMP2, but not MMPs 9 and 1, significantly reduced vessel
      diameters, suggesting that diameter may be MMP2 mediated. Furthermore,
      immunofluorescent staining for membrane bound membrane type 1 (MT1)-MMP showed
      that it was localized to active tip cells. Since MT1-MMP is an important
      activator of MMP2, these findings suggest that MMP2 produced/activated at the tip
      cell may be a dominant mediator of matrix proteolysis and sprout diameter. To
      support this hypothesis, we built a computational reaction-diffusion model
      involving tip cell localized expression of soluble MMPs during sprout elongation.
      The model, consisting of three parameters based on published values for MMP2 and
      one quantitatively tuned parameter, reproduced the experimentally observed
      inverse relationship between elongation rate and vessel diameter. Our
      experimental findings coupled with our computational model suggest a dominant
      mechanism by which elongation rate and soluble MMPs govern nascent vessel
      diameter.

PMID- 22847075
TI  - Transposon insertion in a cinnamyl alcohol dehydrogenase gene is responsible for
      a brown midrib1 mutation in maize.
AB  - Maize brown midrib1 (bm1) mutant plants have reduced lignin content and offer
      significant advantages when used in silage and biofuel applications. Cinnamyl
      alcohol dehydrogenase (CAD) catalyzes the conversion of hydroxycinnamyl aldehydes
      to monolignols, a key step in lignin biosynthesis. Maize CAD2 has been implicated
      as the underlying gene for bm1 phenotypes since bm1 plants have reduced CAD
      activity and lower CAD2 transcript level. Here, we describe a Dow AgroSciences
      maize bm1 mutant (bm1-das1) that contains a 3,444-bp transposon insertion in the
      first intron of CAD2 gene. As a result of chimeric RNA splicing, cad2 mRNA from
      bm1-das1 contains a 409-bp insert between its 1st and 2nd exons. This insertion
      creates a premature stop codon and is predicted to result in a truncated protein
      of 48 amino acids (AA), compared to 367 AA for the wild type (WT) CAD2. We have
      also sequenced cad2 from the reference allele bm1-ref in 515D bm1 stock and
      showed that it contains a two-nucleotide (AC) insertion in the 3rd exon, which is
      predicted to result in a truncated protein of 147 AA. The levels of cad2 mRNA in
      the midribs of bm1-das1 and bm1-ref are reduced by 91 and 86 % respectively,
      leading to reductions in total lignin contents by 24 and 30 %. Taken together,
      our data show that mutations in maize CAD2 are responsible for maize bm1
      phenotypes. Based on specific changes in bm1-das1 and bm1-ref, high throughput
      TaqMan and KBioscience's allele specific PCR assays capable of differentiating
      mutant and WT alleles have been developed to accelerate bm1 molecular breeding.

PMID- 22847076
TI  - Foreword for 2011 Advanced Technology Applications for Combat Casualty Care.

PMID- 22847077
TI  - Use of a novel abdominal aortic tourniquet to reduce or eliminate flow in the
      common femoral artery in human subjects.
AB  - BACKGROUND: Penetrating injuries of proximal femoral and iliac vessels are a
      common cause of death on the battlefield. Previous studies have shown that by
      applying 80 lb to 140 lb of pressure externally over the distal abdominal aorta,
      flow can be ceased in the common femoral artery (CFA). It has also been
      demonstrated that in a porcine model, an externally applied pneumatic abdominal
      aortic tourniquet (AAT) can occlude the aorta and inferior vena cava for 60
      minutes without bowel injury or significant potassium elevations.The objectives
      of this study were (1) determine if AAT use in humans results in flow cessation
      in the CFA, (2) measure the pressure required to cease flow in the CFA, and (3)
      measure discomfort associated with application of the AAT. METHODS: Pulse wave
      Doppler measurements were taken in supine volunteers at the right CFA. The AAT
      was placed just above the iliac crests over the anterior abdomen. The AAT was
      inflated using a hand pump with an integrated manometer. Measurements were taken
      every 30 mm Hg. Discomfort was measured using a 10-point pain scale. RESULTS: In
      all subjects, flow was reduced in the CFA. Flow ceased in seven of nine subjects
      at a median pressure of 180 mm Hg (150-230 mm Hg). Median discomfort at ceasing
      of flow was 7 (3-10), returning to 0 after device removal. CONCLUSION: The AAT
      device was effective at reducing flow in the CFA and ceased flow in most of the
      subjects. Application of the device was associated with discomfort varying from
      moderate to severe and resolving with device removal.

PMID- 22847078
TI  - Lightweight noninvasive trauma monitor for early indication of central
      hypovolemia and tissue acidosis: a review.
AB  - BACKGROUND: Hemorrhage is a major cause of soldier death; it must be quickly
      identified and appropriately treated. We developed a prototype patient monitor
      that noninvasively and continuously determines muscle oxygen saturation (SmO2),
      muscle pH (pHm), and a regional assessment of blood volume (HbT) using near
      infrared spectroscopy. Previous demonstration in a model of progressive, central
      hypovolemia induced by lower body negative pressure (LBNP) showed that SmO2
      provided an early indication of impending hemodynamic instability in humans. In
      this review, we expand the number of subjects and provide an overview of the
      relationship between the muscle and sublingual microcirculation in this model of
      compensated shock. METHODS: Healthy human volunteers (n = 30) underwent
      progressive LBNP in 5-minute intervals. Standard vital signs, along with stroke
      volume (SV), total peripheral resistance, functional capillary density, SmO2,
      HbT, and pHm were measured continuously throughout the study. RESULTS AND
      DISCUSSION: SmO2 and SV significantly decreased during the first level of central
      hypovolemia (-15 mm Hg LBNP), whereas vital signs were later indicators of
      impending cardiovascular collapse. SmO2 declined with SV and inversely with total
      peripheral resistance throughout LBNP. HbT was correlated with declining
      functional capillary density, suggesting vasoconstriction as a cause for
      decreased SmO2 and subsequently decreased pHm. CLINICAL TRANSLATION: The monitor
      has been miniaturized to a 58-g solid-state sensor that is currently being
      evaluated on patients with dengue hemorrhagic fever. Early results demonstrate
      significant decreases in SmO2 similar to those observed with progressive
      reductions in central blood volume. As such, this technology has the potential to
      (1) provide a monitoring capability for both nontraumatic and traumatic
      hemorrhage and (2) help combat medics triage casualties and monitor patients
      during lengthy transport from combat areas.

PMID- 22847079
TI  - Deployment after limb salvage for high-energy lower-extremity trauma.
AB  - BACKGROUND: Many wounded warriors experienced high-energy lower-extremity trauma
      (HELET) that may be limb threatening. Volumetric muscle loss, posttraumatic
      osteoarthritis, nerve injuries, and pain may severely limit physical function.
      Several wounded warriors express a strong desire to return to their units and be
      deployed in their original military occupational specialty. We began the return
      to-run (RTR) clinical pathway at our institution 2 years ago to facilitate high
      performance goals such as these. It involves an energy storing ankle foot
      orthosis, the intrepid dynamic exoskeletal orthosis in combination with high
      intensity, progression-oriented rehabilitation. We sought to determine the rate
      of deployment or predeployment training after participation in this noninvasive
      intervention. METHODS: A retrospective analysis of the RTR database was performed
      to determine the rate of deployment or predeployment training among those service
      members who began participation in the RTR between November of 2009 and March of
      2011. Medical records were reviewed for demographics, injury, surgical data, and
      major complications. Requests for delayed amputation were recorded, and charts
      were reviewed to determine if patients eventually elected to proceed with
      amputation or if they chose to continue with limb salvage. RESULTS: Between
      November 2009 and March 2011, 87 service members completed the RTR. Of these, 17
      (19.5%) have been deployed to combat or are in predeployment training. Sixteen
      serve in combat arms (nine Special Forces, four infantry/ranger, two combat
      engineers, and one gunner), and one is a member of the military intelligence
      community. Fifteen patients sustained their injuries as a result of HELET (four
      gunshot, five motor vehicle collisions, four explosions, one parachute injury,
      and one fall from height), one had idiopathic avascular necrosis of the talus,
      and one had an iatrogenic nerve injury after pelvic surgery. Six of the patients
      underwent circular external fixation, five received joint fusions (three ankle,
      two subtalar joint), and nine had major nerve injuries. Four initially desired
      amputation of their injured limb but have subsequently countermanded their
      request. CONCLUSION: Returning to high-level physical function after HELET is
      challenging. After implementation of the RTR clinical pathway with the intrepid
      dynamic exoskeletal orthosis, 19.5% of wounded warriors treated with the RTR have
      been deployed or will be deployed in the coming year.

PMID- 22847080
TI  - Functional improvements in traumatic scars and scar contractures using an
      ablative fractional laser protocol.
AB  - BACKGROUND: Reports describing the use of ablative fractional resurfacing (AFR)
      for cosmetic improvements in skin dyschromia, rhytides, and textural
      irregularities are becoming increasingly common in the literature. However, the
      is little mention of its functional impact on patients with traumatic scars and
      scar contractures. We present our experience treating scars with AFR,
      highlighting four illustrative cases and providing a review on possible
      mechanisms. METHODS: Up to three ablative fractional carbon dioxide laser
      treatments were performed at 1-month to 2-month intervals on four patients with
      functional deficits related to refractory scar contractures. Treatments were
      individualized and began as early as 2 months after injury or final
      reconstructive surgery. Cases were performed in the outpatient clinic using
      topical anesthetic supplemented by forced air cooling. Postprocedure care
      included diluted-vinegar compresses two to three times daily and application of
      ointment over the treatment area for approximately 3 days after the procedure.
      Postprocedure pain was minimal, and all patients were allowed to resume physical
      therapy as early as the day of treatment. RESULTS: AFR was well tolerated without
      serious complications. Durable and cumulative improvements in range of motion or
      overall skin functionality were noted in all patients. AFR can be surgery sparing
      and facilitated earlier return to full or modified activities based on associated
      injuries. CONCLUSION: AFR is a novel, well tolerated, and effective complement to
      traditional rehabilitative management for patients with traumatic scars and scar
      contractures. Potential paradigm shifts include earlier initiation of treatment
      and a focus on functional improvements.

PMID- 22847081
TI  - TBI risk stratification at presentation: a prospective study of the incidence and
      timing of radiographic worsening in the Parkland Protocol.
AB  - BACKGROUND: We have created a theoretical algorithm for venous thromboembolism
      prophylaxis after traumatic brain injury (TBI) known as the Parkland Protocol,
      which stratifies patients into low-, medium-, and high-risk categories for
      spontaneous progression of hemorrhage. This prospective study characterizes the
      incidence and timing of radiographic progression of the TBI patterns in these
      categories. METHODS: Inclusion criterion was presentation with intracranial blood
      between February 2010 and March 2011; exclusion was receipt of only one computed
      tomographic scan of the head during the inpatient stay or preinjury warfarin. At
      admission, all patients were preliminarily categorized per the Parkland Protocol
      as follows: low risk (LR), patients meeting the modified Berne-Norwood criteria;
      moderate risk (MR), injuries larger than the modified Berne-Norwood criteria
      without requiring a neurosurgical procedure; high risk (HR), any patient with a
      craniotomy/monitor. RESULTS: A total of 245 patients with intracranial hemorrhage
      were enrolled during the 13-month study period. Of patients preliminarily
      classified as LR at admission (n = 136), progression was seen in 25.0%.
      Spontaneous worsening was seen in 7.4% of LR patients at 24 hours after injury,
      and no LR patients progressed at 72 hours after injury. In patients initially
      classified as MR at admission (n = 42), progression was seen in 42.9%, with 91.5%
      of patients demonstrating stable computed tomographic head scans at 72 hours
      after injury. In patients initially classified as HR (n = 67), 64.2% demonstrated
      spontaneous progression of their TBI patterns, with 10.5% continuing to progress
      at 72 hours after injury. Most repeat scans were performed as routinely scheduled
      studies (81-91%). CONCLUSION: Increases in the incidence of spontaneous worsening
      were seen as severities of injury progressed from the Parkland Protocol's LR to
      MR to HR arms. The time frames for these spontaneous worsenings seem to be such
      that the protocol's theoretical recommendations for venous thromboembolism
      prophylaxis are worth pursuing as future points of investigation.

PMID- 22847082
TI  - Resuscitation with washed aged packed red blood cell units decreases the
      proinflammatory response in mice after hemorrhage.
AB  - BACKGROUND: Resuscitation with blood products instead of crystalloid in the
      treatment of hemorrhagic shock has been associated with improved outcomes in
      trauma patients requiring massive transfusions and transfusion of fresh products
      results in reduced morbidity and mortality compared with aged blood. Processes to
      eliminate harmful components of aged blood are under investigation. We
      hypothesized that washing blood would reduce levels of proinflammatory mediators
      in stored units, and resuscitation with washed units would attenuate the
      proinflammatory response in mice after hemorrhagic shock. METHODS: Mice underwent
      pressure-controlled hemorrhage and resuscitation with fresh packed red blood
      cells (pRBCs) or 15-day-old washed or unwashed pRBCs. Cytokine concentrations in
      donor samples and recipient serum were measured. In addition, cytokine
      concentrations were measured in 15-day-old units that underwent three interval
      washes versus one poststorage wash. RESULTS: Blood stored for 15 days
      demonstrated increased levels of interleukin 1alpha, keratinocyte
      chemoattractant, macrophage inflammatory protein 1alpha, and macrophage
      inflammatory protein 2 compared with fresh units. Washing 15-day-old pRBCs
      reduced concentrations of these cytokines. Cytokine levels in stored units that
      underwent multiple washes versus a single wash were not different. Mice
      resuscitated with 15-day-old unwashed pRBCs had increased levels of serum
      cytokines compared with mice resuscitated with fresh and 15-day-old washed pRBCs.
      CONCLUSION: Aged pRBC units have elevated levels of proinflammatory cytokines
      compared with fresh units, and washing aged units after storage reduces cytokine
      concentrations. Resuscitation with washed units blunts the proinflammatory
      response in mice after hemorrhage. Washing aged pRBCs may improve the safety
      profile of aged units and may result in improved outcomes in subjects after
      hemorrhagic shock and resuscitation.

PMID- 22847083
TI  - Is a diagnosis of "mild traumatic brain injury" a category mistake?
AB  - BACKGROUND: Efforts to produce definitions and diagnostic standards for mild
      traumatic brain injury (TBI) have a long and complex history. The diagnosis of
      TBI must be considered in the larger context of neuropsychiatric diagnosis. A
      major reconceptualization of diagnosis is now underway in which the classical
      syndrome conceptualization is being discarded. We address the question, what are
      the implications of this revision of thinking in the specific context of TBI?
      METHODS: A recent literature on logical structures for neuropsychiatric disorders
      was reviewed. The symptom pattern of TBI was identified, and a literature survey
      determined the frequency of these symptom patterns in other disorders and in
      healthy control populations. RESULTS: The frequency of symptom endorsement in
      populations without a history of TBI can be equal to endorsement frequencies in
      populations with a history of mild TBI. In some studies, the frequency of symptom
      endorsement in healthy controls having no history of head injury actually
      exceeded the endorsement rates in a comparison group with a history mild TBI.
      CONCLUSION: The heterogeneity of this clinical population and their clinical
      presentations, the absence of a unitary etiology of postinjury deficits, and the
      complex idiosyncratic time course of the appearance of these deficits argue
      against the valid implementation of the classical model of diagnosis. In
      addition, the accepted criteria of diagnostic utility are not satisfied. TBI is
      not a disease; it is an event. More precisely, TBI is an event or a sequence of
      events that can, in some instances, lead to a diagnosable neurological or
      psychiatric disorder.

PMID- 22847084
TI  - A novel sponge-based wound stasis dressing to treat lethal noncompressible
      hemorrhage.
AB  - BACKGROUND: Noncompressible hemorrhage is the leading cause of preventable death
      caused by hemorrhage on the battlefield. Currently, there are no hemostatic
      agents with the ability to control noncompressible hemorrhage. A wound stasis
      dressing based upon rapidly expanding cellulose minisponges (MS) was developed
      and tested in a lethal noncompressible model in swine, by fully transecting
      subclavian artery and vein. MS were compared with conventional hemostasis
      dressings, Combat Gauze (CG), in a randomized comparison. METHODS: Sixteen 40-kg
      swine underwent transection of the subclavian artery and vein through a 4.5-cm
      aperture. After 30-second free bleeding, randomly selected MS or CG (n = 8 per
      group) were administered by an independent medical officer. The wound cavity was
      filled with either MS + no external pressure or one CG + one KERLIX gauze with 3
      minutes of external pressure. One reapplication was allowed for CG. Mean arterial
      pressure was maintained at 60 mm Hg with 500-mL Hextend and lactated Ringer's
      solution intravenously administered up to a maximum of 10-L until study
      termination at 1 hour. RESULTS: Mean pretreatment blood loss was similar for MS
      (719 mL) and CG (702 mL). Primary end points, namely, hemostasis at 4 minutes
      (MS, 75%; CG, 25%; p = 0.13), hemostasis at 60 minutes (MS, 100%; CG, 25%; p =
      0.007), and survival at 60 minutes (MS, 100%; CG, 37.5%; p = 0.026), were
      improved with MS as were secondary end points, namely, total blood loss (MS, 118
      mL; CG 1,242 mL; p = 0.021) and length of application time (MS, 25 seconds; CG,
      420 seconds; p = 0.004). CONCLUSION: The use of MS is a novel approach for the
      rapid, simple treatment of severe noncompressible hemorrhage, which provided
      statistically significant improvement in hemostasis and survival 60 minutes after
      injury and a large reduction in blood loss, resuscitation fluid requirement, and
      medic treatment time compared with conventional hemorrhage control dressings in a
      swine model.

PMID- 22847085
TI  - Continuous measurement of cerebral oxygen saturation (rSO2) for assessment of
      cardiovascular status during hemorrhagic shock in a swine model.
AB  - BACKGROUND: Early trauma care is dependent on subjective assessments and sporadic
      vital sign assessments. We hypothesized that near-infrared spectroscopy-measured
      cerebral oxygenation (regional oxygen saturation [rSO2]) would provide a tool to
      detect cardiovascular compromise during active hemorrhage. We compared rSO2 with
      invasively measured mixed venous oxygen saturation (SvO2), mean arterial pressure
      (MAP), cardiac output, heart rate, and calculated pulse pressure. METHODS: Six
      propofol-anesthetized instrumented swine were subjected to a fixed-rate
      hemorrhage until cardiovascular collapse. rSO2 was monitored with noninvasively
      measured cerebral oximetry; SvO2 was measured with a fiber optic pulmonary
      arterial catheter. As an assessment of the time responsiveness of each variable,
      we recorded minutes from start of the hemorrhage for each variable achieving a
      5%, 10%, 15%, and 20% change compared with baseline. RESULTS: Mean time to
      cardiovascular collapse was 35 minutes +/- 11 minutes (54 +/- 17% total blood
      volume). Cerebral rSO2 began a steady decline at an average MAP of 78 mm Hg +/-
      17 mm Hg, well above the expected autoregulatory threshold of cerebral blood
      flow. The 5%, 10%, and 15% decreases in rSO2 during hemorrhage occurred at a
      similar times to SvO2, but rSO2 lagged 6 minutes behind the equivalent percentage
      decreases in MAP. There was a higher correlation between rSO2 versus MAP (R2
      =0.72) than SvO2 versus MAP (R2 =0.55). CONCLUSIONS: Near-infrared spectroscopy
      measured rSO2 provided reproducible decreases during hemorrhage that were similar
      in time course to invasively measured cardiac output and SvO2 but delayed 5 to 9
      minutes compared with MAP and pulse pressure. rSO2 may provide an earlier warning
      of worsening hemorrhagic shock for prompt interventions in patients with trauma
      when continuous arterial BP measurements are unavailable.

PMID- 22847086
TI  - Metabolomics classifies phase of care and identifies risk for mortality in a
      porcine model of multiple injuries and hemorrhagic shock.
AB  - BACKGROUND: Early recognition and intervention in hemorrhagic shock is essential
      to improved outcomes. However, the lack of robust diagnostic tools readily
      available to identify patients in the field inhibits the ability to provide
      timely intervention. Therefore, the development of a reliable prognostic
      indicator, such as a serum biomarker or a metabolic profile, has significant
      potential to improve far-forward trauma care. In this study, we used metabolomics
      as a tool to identify a metabolic state associated with the hemorrhagic shock and
      outcome in our porcine model of multiple injuries, shock, and resuscitation.
      METHODS: Proton nuclear magnetic resonance spectroscopy was used to evaluate
      serum metabolites from 23 animals that underwent multiple injuries, controlled
      hemorrhage, and 20 hours of a standard resuscitation protocol. Serum samples were
      collected from the animals at baseline (before hemorrhage), at shock (after 45
      minutes of shock), and at 8 hours of full resuscitation. RESULTS: We were able to
      demonstrate shifts in the metabolome throughout different time points and
      construct a metabolic profile associated with mortality using partial least
      squares discriminate analysis. The metabolites most responsible for the
      classification of hemorrhagic shock in our model serve as markers for ischemia,
      changes in energy production, and cellular damage. Hemorrhagic shock was
      characterized by marked increases in tricarboxylic acid cycle intermediates,
      glycolytic-gluconeogenic by-products, purine-pyrimidine catabolism, and fatty
      acid oxidation. CONCLUSION: The results of this study demonstrate the potential
      for metabolomics as a tool to classify the metabolic flux, to identify relevant
      biochemical pathways, and to identify clinically useful biomarkers.

PMID- 22847087
TI  - Long-term administration of amnion-derived cellular cytokine suspension promotes
      functional recovery in a model of penetrating ballistic-like brain injury.
AB  - BACKGROUND: Previous work has shown that human amnion-derived progenitor (AMP)
      cell therapy is neuroprotective in a penetrating ballistic-like brain injury
      (PBBI) model. However, the neuroprotective capacity of AMP cells seemed to be
      mediated by the sustained secretion of AMP cell-derived neurotrophic factors,
      which are abundant in the amnion-derived cellular cytokine suspension (ACCS). To
      test this theory, the current study assessed the neuroprotective efficacy of long
      term ACCS delivery in the PBBI model. METHODS: Experiment 1 assessed the
      bioactive stability and neuroprotective capacity of ACCS in an in vitro model of
      neurodegeneration. Experiment 2 evaluated the therapeutic effects of ACCS
      delivery initiated 15 minutes after PBBI and continued for 2 weeks after injury.
      Experiment 3 was designed to identify the therapeutic window for long-term ACCS
      delivery in the PBBI model. Outcome metrics included neurobehavioral assessments
      and neuropathologic measures of neuroinflammation and axonal/neuronal
      degeneration. RESULTS: Experiment 1 demonstrated that ACCS is thermally stable
      for 1 week at 37 degrees C and that ACCS treatment protected neurite against
      staurosporine toxicity. Experiment 2 identified the optimal infusion rate of ACCS
      (1 MUL/h) and demonstrated that long-term infusion of ACCS was capable of
      promoting significant protection against PBBI-induced neuropathology and motor
      abnormalities, but was not sufficient for reducing cognitive deficits. Finally,
      the results of Experiment 3 showed that ACCS is effective in promoting
      significant neuroprotection even when onset of treatment is delayed out to 24
      hours (but not 48 hours) after PBBI. CONCLUSIONS: Collectively, our results
      support the hypothesis that the neuroprotective effects of AMP cells are mediated
      through a sustained delivery of ACCS, which implicates ACCS as a promising
      neuroprotection agent for clinical study.

PMID- 22847088
TI  - Treatment with low-dose methamphetamine improves behavioral and cognitive
      function after severe traumatic brain injury.
AB  - BACKGROUND: Methamphetamine increases the release and blocks the reuptake of
      dopamine. The moderate activation of dopamine receptors may elicit
      neuroprotective effects. We have recently demonstrated that low doses of
      methamphetamine reduce neuronal loss after ischemic injury. On the basis of this
      finding, we hypothesized that methamphetamine could also prevent neuronal loss
      and improve functional behavior after severe traumatic brain injury (TBI).
      METHODS: The rat lateral fluid percussion injury model was used to generate
      severe TBI. Three hours after injury, animals were treated with saline or
      methamphetamine. Neurological severity scores and foot fault assessments were
      used to determine whether treatment enhanced recovery after injury. The potential
      for methamphetamine treatment to improve cognitive function was assessed using
      the Morris water maze. Forty-eight hours after injury, paraffin-embedded brain
      sections were TUNEL stained to measure apoptotic cell death. Sections were also
      stained with antibody to doublecortin to quantify immature neurons within the
      dentate gyrus. RESULTS: Treatment with low-dose methamphetamine significantly
      reduced both behavioral and cognitive dysfunction after severe TBI.
      Methamphetamine-treated animals scored significantly lower on neurological
      severity scores and had significantly less foot faults after TBI compared with
      saline-treated control rats. Furthermore, methamphetamine treatment restored
      learning and memory function to near normal ability after TBI. At 48 hours after
      injury, apoptotic cell death within the hippocampus was significantly reduced,
      and the presence of immature neurons was significantly increased in
      methamphetamine-treated rats compared with saline-treated controls. CONCLUSION:
      Treatment with low-dose methamphetamine after severe TBI elicits a robust
      neuroprotective response resulting in significant improvements in behavioral and
      cognitive functions.

PMID- 22847089
TI  - Improvised explosive device related pelvi-perineal trauma: anatomic injuries and
      surgical management.
AB  - BACKGROUND: Pelviperineal injuries, primarily due to blast mechanisms, are
      becoming the signature injury pattern on operations in Afghanistan. This study
      set out to define these injuries and to refine our team-based surgical
      resuscitation strategies to provide a resuscitation-debridement-diversion
      didactic on our Military Operational Surgical Training predeployment course to
      optimize our field care of these injuries. METHODS: A retrospective study of the
      UK Joint Theatre Trauma Registry was performed looking at consecutive data from
      January 2003 to December 2010, identifying patients with perineal injuries. Data
      abstracted included patient demographics, mechanism of injury, Injury Severity
      Score (ISS), management, and outcomes. RESULTS: Of 2204 UK military trauma
      patients, 118 (5.4%) had a recorded perineal injury and 56 (47%) died . Pelvic
      fractures were identified in 63 (53%) of 118 patients of which only 17 (27%) of
      63 survived. Mortality rates were significantly different between the combined
      perineal and pelvic fracture group compared with the pelvic fractures or perineal
      injuries alone (107 [41%] of 261 and 11 [18%] of 56, respectively, p < 0.001).
      The median (interquartile range) ISS for all patients was 38 (29-57). The ISS for
      those with pelvic fractures were significantly higher than those with perineal
      injuries alone, 50 (38-71) versus 30 (15-35) (p < 0.001). CONCLUSION: Improvised
      explosive device-related perineal injuries with pelvic fractures had the highest
      rate of mortality compared with perineal injuries alone. Early aggressive
      resuscitation (activation of the massive hemorrhage protocol) is essential to
      survival in this cohort. Our recommendations are uncompromising initial
      debridement, immediate fecal diversion, and early enteral feeding.

PMID- 22847090
TI  - The Battlefield Health and Trauma Research Institute Scientific Ethics Committee:
      an evolving model for fostering a culture of integrity.

PMID- 22847091
TI  - Impact of critical care-trained flight paramedics on casualty survival during
      helicopter evacuation in the current war in Afghanistan.
AB  - BACKGROUND: The US Army pioneered medical evacuation (MEDEVAC) by helicopter, yet
      its system remains essentially unchanged since the Vietnam era. Care is provided
      by a single combat medic credentialed at the Emergency Medical Technician - Basic
      level. Treatment protocols, documentation, medical direction, and quality
      improvement processes are not standardized and vary significantly across US Army
      helicopter evacuation units. This is in contrast to helicopter emergency medical
      services that operate within the United States. Current civilian helicopter
      evacuation platforms are routinely staffed by critical care-trained flight
      paramedics (CCFP) or comparably trained flight nurses who operate under trained
      EMS physician medical direction using formalized protocols, standardized patient
      care documentation, and rigorous quality improvement processes. This study
      compares mortality of patients with injury from trauma between the US Army's
      standard helicopter evacuation system staffed with medics at the Emergency
      Medical Technician - Basic level (standard MEDEVAC) and one staffed with
      experienced CCFP using adopted civilian helicopter emergency medical services
      practices. METHODS: This is a retrospective study of a natural experiment. Using
      data from the Joint Theater Trauma Registry, 48-hour mortality for severely
      injured patients (injury severity score >= 16) was compared between patients
      transported by standard MEDEVAC units and CCFP air ambulance units. RESULTS: The
      48-hour mortality for the CCFP-treated patients was 8% compared to 15% for the
      standard MEDEVAC patients. After adjustment for covariates, the CCFP system was
      associated with a 66% lower estimated risk of 48-hour mortality compared to the
      standard MEDEVAC system. CONCLUSIONS: These findings demonstrate that using an
      air ambulance system based on modern civilian helicopter EMS practice was
      associated with a lower estimated risk of 48-hour mortality among severely
      injured patients in a combat setting.

PMID- 22847092
TI  - Prehospital interventions performed in a combat zone: a prospective multicenter
      study of 1,003 combat wounded.
AB  - BACKGROUND: Battlefield care given to a casualty before hospital arrival impacts
      clinical outcomes. To date, the published data regarding care given in the
      prehospital setting of a combat zone are limited. The purpose of this study was
      to describe the incidence and efficacy of specific prehospital lifesaving
      interventions (LSIs; interventions that could affect the outcome of the
      casualty), consistent with the Tactical Combat Casualty Care paradigm, performed
      during the resuscitation of casualties in a combat zone. METHODS: We performed a
      prospective observational study between November 2009 and November 2011.
      Casualties were enrolled as they were treated at six US surgical facilities in
      Afghanistan. Descriptive data were collected on a standardized data collection
      form and included mechanism of injury, airway management, chest and hemorrhage
      interventions, vascular access, type of fluid administered, and hypothermia
      prevention. On arrival to the military hospital, the treating physician
      determined whether an intervention was performed correctly and whether an
      intervention was not performed that should have been performed (missed LSI).
      RESULTS: A total of 1,003 patients met the inclusion criteria. Their mean (SD)
      age was 25 (8.5) years and 97% were male. The mechanism of injury was explosion
      in 60% of patients, penetrating in 24% of patients, blunt in 15% of patients, and
      burn in 0.8% of patients. The most commonly performed LSIs included hemorrhage
      control (n = 599), hypothermia prevention (n = 429), and vascular access (n =
      388). Of the missed LSIs, 252 were identified with the highest percentage of
      missed opportunities being composed of endotracheal intubation, chest needle
      decompression, and hypotensive resuscitation. In contrast, tourniquet application
      had the lowest percentage of missed opportunities. CONCLUSIONS: In our
      prospective study of prehospital LSIs performed in a combat zone, we observed a
      higher rate of incorrectly performed and missed LSIs in airway and chest
      (breathing) interventions than hemorrhage control interventions. The most
      commonly performed LSIs had lower incorrect and missed LSI rates.

PMID- 22847093
TI  - The effects of standardized trauma training on prehospital pain control: have
      pain medication administration rates increased on the battlefield?
AB  - BACKGROUND: The US Military has served in some of the most austere locations in
      the world. In this ever-changing environment, units are organized into smaller
      elements operating in very remote areas. This often results in longer evacuation
      times, which can lead to a delay in pain management if treatment is not initiated
      in the prehospital setting. Early pain control has become an increasingly crucial
      military prehospital task and must be controlled from the pain-initiating event.
      The individual services developed their standardized trauma training based on the
      recommendations by Frank Butler and the Defense Health Board Committee on
      Tactical Combat Casualty Care. This training stresses evidence-based treatment
      modalities, including pain control, derived from casualty injury analysis.
      Inadequate early pain control may lead to multiple acute and potentially chronic
      effects. These effects encompass a wide range from changes in blood pressure to
      delayed wound healing and posttraumatic stress disorder. Therefore, it is
      essential that pain be addressed in the prehospital environment. METHODS:
      Institutional Review Board approval was obtained to conduct a retrospective Joint
      Theater Trauma Registry comparative study evaluating whether standardized trauma
      training increased prehospital pain medication administration between 2007 and
      2009. These years were selected on the basis of mandatory training initiation
      dates and available Joint Theater Trauma Registry records. Records were analyzed
      for all US prehospital trauma cases with documented pain medication
      administration from Operations Enduring Freedom and Iraqi Freedom for the
      specified years. RESULTS: Data analysis revealed 232 patients available for
      review (102 for 2007 and 130 for 2009). A statistically significant prehospital
      pain treatment increase was noted, from 3.1% in 2007 to 6.7% in 2009 (p < 0.0005;
      95% confidence interval, 2.39-4.93). CONCLUSION: Standardized trauma training has
      increased the administration of prehospital pain medication and the awareness of
      the importance of early pain control.

PMID- 22847094
TI  - The effects of prehospital plasma on patients with injury: a prehospital plasma
      resuscitation.
AB  - BACKGROUND: The prehospital resuscitation of the exsanguinating patient with
      trauma is time and resource dependent. Rural trauma care magnifies these factors
      because transportation time to definitive care is increased. To address the early
      resuscitation needs and trauma-induced coagulopathy in the exsanguinating patient
      with trauma an aeromedical prehospital thawed plasma-first transfusion protocol
      was used. METHODS: Retrospective review of trauma and flight registries between
      February 1, 2009, and May 31, 2011, was performed. The study population included
      all patients with traumatic injury transported by rotary wing aircraft who met
      criteria for massive transfusion protocol RESULTS: A total of 59 patients
      identified over 28 months met criteria for initiation of aeromedical initiation
      of prehospital blood product resuscitation. Nine patients received thawed plasma
      first protocol compared with 50 controls. The prehospital plasma group was more
      commonly on warfarin (22 vs. 2%, p = 0.036) and had a greater degree of
      coagulopathy measured by international normalized ratio at baseline (2.6 vs. 1.5,
      p = 0.004) and trauma center arrival (1.6 vs. 1.3, p < 0.001). The prehospital
      plasma group had a predicted mortality nearly three times greater than controls
      based on Trauma and Injury Severity Score (0.24 vs. 0.66, p = 0.005). The use of
      prehospital plasma resuscitation led to a plasma-red blood cell ratio that more
      closely approximated a 1:1 resuscitation en route (1.3:1.0 vs. not applicable, p
      < 0.001), at 30 minutes (1.3:1.0 vs. 0.14:1.0, p < 0.001), at 6 hours (0.95:1.0
      vs. 0.42:1.0, p < 0.001), and at 24 hours (1.0:1.0 vs. 0.45:1.0, p < 0.001). An
      equivalent amount of packed red blood cells were transfused between the groups.
      Despite more significant hypotension, less crystalloid was used in the
      prehospital thawed plasma group, through 24 hours after injury (6.3 vs. 16.4 L, p
      = 0.001). CONCLUSION: Use of plasma-first resuscitation in the helicopter system
      creates a field ready, mobile blood bank, allowing early resuscitation of the
      patient demonstrating need for massive transfusion. There was early treatment of
      trauma-induced coagulopathy. Although there was not a survival benefit
      demonstrated, there was resultant damage control resuscitation extending to 24
      hours in the plasma-first cohort.

PMID- 22847095
TI  - Use of respiratory impedance in prehospital care of hypotensive patients
      associated with hemorrhage and trauma: a case series.
AB  - BACKGROUND: The respiratory pump can be optimized to enhance circulation in
      patients with hypotension by having patients spontaneously breathe through a low
      level of inspiratory resistance. This can be achieved with an impedance threshold
      device (ITD) designed to provide 7 cm H2O resistance during spontaneous
      inspiration with minimal resistance during expiration. Little is known about the
      effects of harnessing this physiological concept to increase blood pressure (BP)
      in the prehospital setting of care for patients with hypotension caused by blood
      loss or trauma. In this case series, we report on the feasibility, effectiveness,
      and safety of rapidly deploying the ITD by first responders to treat hypotension
      secondary to blood loss and trauma in the urban setting by emergency medical
      services personnel. METHODS: Hemodynamic data from hypotensive patients
      (pretreatment systolic BP [SBP] <100 mm Hg) from 3 U.S. cities where the ITD is
      deployed were evaluated. The primary end point was maximum change in SBP and
      diastolic BP (DBP) from before to during ITD use in patients with hypotension
      secondary to documented blood loss or trauma. Secondary end points were device
      tolerance, whether the patient felt "better," change in heart rate, O2
      saturation, and adverse events. RESULTS: Of the 255 hypotensive patients treated,
      there were 26 categorized with blood loss and 13 with trauma. In this 39-patient
      subgroup, the SBP and DBP (mean +/- SD) increased from 79 +/- 14 mm Hg and 48 +/-
      12 mm Hg before ITD placement to 110 +/- 17 mm Hg and 66 +/- 14 mm Hg after ITD
      placement (p < 0.001). Breathing through the ITD resulted in no reported adverse
      events, was well tolerated, and resulted in feeling "better" in more than 85% of
      the patients. CONCLUSION: Use of an ITD by emergency medical services personnel
      on hypotensive spontaneously breathing patients secondary to blood loss and
      trauma increased SBP and DBP and was feasible, well tolerated, and not associated
      with adverse effects (e.g., increased bleeding).

PMID- 22847096
TI  - Interpreting comparative died of wounds rates as a quality benchmark of combat
      casualty care.
AB  - BACKGROUND: The died of wounds (DOW) rate is cited as a measure of combat
      casualty care effectiveness without the context of injury severity or insight
      into lethality of the battlefield. The objective of this study was to
      characterize injury severity and other factors related to variations in the DOW
      rate. METHODS: The highest monthly DOW (HDOW) and lowest monthly DOW (LDOW) rates
      from 2004 to 2008 were identified from analysis and casualty report databases and
      used to direct a search of the Joint Theater Trauma Registry. Casualties from the
      HDOW and LDOW were combined into cohorts, and injury data were analyzed and
      compared. RESULTS: The HDOW rates were 13.4%, 11.6%, and 12.8% (mean, 12.6%), and
      the LDOW rates were 1.3%, 2.0%, and 2.7% (mean, 2.0%) (p < 0.0001). The HDOW (n =
      541) and LDOW (n = 349) groups sustained a total of 1,154 wounds. Injury Severity
      Score was greater in the HDOW than the LDOW group (mean [SD], 11.1 [0.53] vs. 9.4
      [0.58]; p = 0.03) as was the percentage of patients with Injury Severity Score of
      more than 25 (HDOW, 12% vs. LDOW, 7.7%; p = 0.04). Excluding minor injuries
      (Abbreviated Injury Scale score of 1), there was a greater percentage of chest
      injuries in the HDOW compared with the LDOW group (16.5% vs. 11.2%, p = 0.03).
      Explosive mechanisms were more commonly the cause of injury in the HDOW group
      (58.7% vs. 49.7%; p = 0.007), which also had a higher percentage of Marine Corps
      personnel (p = 0.02). CONCLUSION: This study provides novel data demonstrating
      that the died of wounds rate ranges significantly throughout the course of
      combat. Discernible differences in injury severity, wounding patterns, and even
      service affiliation exist within this variation. For accuracy, the died of wounds
      rate should be cited only in the context of associated injury patterns, injury
      severity, and mechanisms of injury. Without this context, DOW should not be used
      as a comparative medical metric.

PMID- 22847097
TI  - Combat readiness for the modern military surgeon: data from a decade of combat
      operations.
AB  - OBJECTIVE: Hundreds of general surgeons from the army, navy, and air force have
      been deployed during the past 10 years to support combat forces, but little data
      exist on their preparedness to handle the challenging injuries that they are
      currently encountering. Our objective was to assess operative and operational
      experience in theater with the goal of improving combat readiness among surgeons.
      METHODS: A detailed survey was sent to 246 active duty surgeons from the army,
      navy, and air force who have been deployed at least once in the past 10 years,
      requesting information on cases performed, perceptions of efficacy of
      predeployment training, knowledge deficits, and postdeployment emotional
      challenges. Survey data were kept confidential and analyzed using standard
      statistical methods. RESULTS: Of 246 individuals, 137 (56%) responded and 93
      (68%) have been deployed two or more times. More than 18,500 operative procedures
      were reported, with abdominal and soft tissue cases predominating. Many surgeons
      identified knowledge or practice gaps in predeployment vascular (46%),
      neurosurgical (29.9%), and orthopedic (28.5%) training. The personal burden of
      deployment manifested itself with both family (approximately 10% deployment
      related divorce rate) and personal (37 surgeons [27%] with two or more symptoms
      of posttraumatic stress syndrome) stressors. CONCLUSION: These data support
      modifications of predeployment combat surgical training to include increased
      exposure to open vascular procedures and curriculum traditionally outside general
      surgery (neurosurgery and orthopedics). The acute care surgical model may be
      ideal for the military surgeon preparing for deployment. Further research should
      be directed toward identifying factors contributing to psychological stress among
      military medics.

PMID- 22847098
TI  - A collaborative research system for functional outcomes following wartime
      extremity vascular injury.

PMID- 22847099
TI  - Combat management of splenic injury: trends during a decade of conflict.
AB  - BACKGROUND: As a performance improvement measure to optimize patient outcome,
      theater-wide clinical practice guidelines (CPGs) have been developed to
      standardize the management of many injury patterns seen during combat operations.
      Battle-related splenic injury presents differently from civilian practice, and a
      combat-related CPG was developed. The epidemiology and validation of the spleen
      injury CPG were analyzed. METHODS: The Joint Theater Trauma Registry was queried
      for splenic injury from 2001 to 2010. Theater of operation (Afghanistan and
      Iraq), injury year, mechanism, patients' baseline characteristics, and severity
      were recorded. Patient charts were reviewed for management decisions and
      outcomes. RESULTS: The 10-year experience identified 393 patients who sustained
      splenic injury (rate of 16.1 per 1000 injuries). Most victims were men (97.5%),
      blunt, and severely injured (70.7%; mean Injury Severity Score, 32.5,
      respectively), with a mean age of 25.4 years. The prominent mechanism was
      explosion (62.2%), followed by vehicle crash (25.9%). The most prevalent injury
      was grade II (56.2%), followed by III (21.1%), IV (11.7%), and V (9.7%). More
      than half of patients underwent splenectomy (52.7%), most of which occurred in
      theater (95.1%). All nonoperative failures were treated within 4 days of injury
      at the role IV facility in Landstuhl. Patients who underwent splenectomy received
      more blood products, crystalloid, and demonstrated a longer length of stay than
      those treated nonoperatively. High-grade injuries treated nonoperatively were
      successfully managed. The overall cohort mortality was 9%, and no death was
      directly related to delayed diagnosis or treatment. CONCLUSION: Splenic injury
      has been successfully managed during combat operations through the use of a well
      established CPG. The overall mortality remains low, with few delayed nonoperative
      failures. Refinements in this validated CPG may now address controversies in
      higher grade injuries.

PMID- 22847100
TI  - Checklists change communication about key elements of patient care.
AB  - BACKGROUND: Combat casualty care is distributed across professions and echelons
      of care. Communication within it is fragmented, inconsistent, and prone to
      failure. Daily checklists used during intensive care unit (ICU) rounds have been
      shown to improve compliance with evidence-based practices, enhance communication,
      promote consistency of care, and improve outcomes. Checklists are criticized
      because it is difficult to establish a causal link between them and their effect
      on outcomes. We investigated how checklists used during ICU rounds affect
      communication. METHODS: We conducted this project in two military ICUs (burn and
      surgical/trauma). Checklists contained up to 21 questions grouped according to
      patient population. We recorded which checklist items were discussed during
      rounds before and after implementation of a "must address" checklist and compared
      the frequency of discussing items before checklist prompting. RESULTS: Patient
      discussions addressed more checklist items before prompting at the end of the 2
      week evaluation compared with the 2-week preimplementation period (surgical
      trauma ICU, 36% vs. 77%, p < 0.0001; burn ICU, 47% vs. 72 %, p < 0.001). Most
      items were addressed more frequently in both ICUs after implementation. Key items
      such as central line removal, reduction of laboratory testing, medication
      reconciliation, medication interactions, bowel movements, sedation holidays,
      breathing trials, and lung protective ventilation showed significant
      improvements. CONCLUSION: Checklists modify communication patterns. Improved
      communication facilitated by checklists may be one mechanism behind their
      effectiveness. Checklists are powerful tools that can rapidly alter patient care
      delivery. Implementing checklists could facilitate the rapid dissemination of
      clinical practice changes, improve communication between echelons of care and
      between individuals involved in patient care, and reduce missed information.

PMID- 22847101
TI  - Percutaneous tracheostomy: a new approach to the emergency airway.
AB  - BACKGROUND: Endotracheal intubation is the preferred method of airway control.
      Current surgical standard of care for the emergent airway when endotracheal
      intubation cannot be performed is cricothyroidotomy. Percutaneous tracheostomy
      (PT) is a widely accepted technique for elective long-term airway management in
      the critical care setting. We describe our experience with successful placement
      of PT for emergency airway control. METHODS: After institutional review board
      approval was obtained, patients were identified retrospectively from January 2003
      to present that had emergency PT performed as identified by the DRG International
      Classification of Diseases--9th Rev. procedure code (31.1). Data included
      demographics, body mass index, admitting service, size of tracheostomy tube,
      reason for urgent airway access, duration PT was required, unit, time and
      hospital day performed, and complications. RESULTS: Eighteen patients underwent
      emergency PT; 61% were male, and age range was 21 years to 86 years. Indications
      for PT included respiratory failure associated with anaphylaxis, supraglottic
      edema, cardiac arrest, and blood or edema blocking the airway preventing
      intubation. PT was performed in various departments throughout the hospital.
      Admitting services included critical care intensivist (44.4%), trauma surgery
      (27.7%), cardiology (11.1%), medicine (11.1%), and neurology (5.5%). Most of the
      tracheostomy tube sizes were no. 8 (61.1%), followed by no. 7 (22.2%), no. 6
      (5.5%), and no. 9 (5.5%). All PTs were successfully placed, and there were no
      complications. Ten of our patients had no airway in place at the time of
      procedure. Six patients had emergency esophageal-tracheal airways in place. Two
      patients had a cricothyroidotomy that was not functioning adequately. Nine
      patients had body mass indexes ranging from 30 kg/m2 to 112 kg/m2. CONCLUSION: PT
      provided a safe, effective emergency airway in adult patients who presented with
      a variety of indications, in varying locations throughout the hospital. PT
      performed by appropriately trained personnel may be a potential adjunct for
      emergent airway control in diverse settings.

PMID- 22847102
TI  - Timing and location of blood product transfusion and outcomes in massively
      transfused combat casualties.
AB  - BACKGROUND: Hemostatic resuscitation using blood components in a 1:1:1 ratio of
      platelets:fresh frozen plasma:red blood cells (RBCs) is based on analyses of
      massive transfusion (MT, >=10 RBC units in 24 hours). These 24-hour analyses are
      weakened by survival bias and do not describe the timing and location of
      transfusions. Mortality outcomes associated with early (first 6 hours)
      resuscitation incorporating platelets, for combat casualties requiring MT, have
      not been reported. METHODS: We analyzed records for 8,618 casualties treated at
      the United States military hospital in Baghdad, Iraq, between January 2004 and
      December 2006. Patients (n = 414) requiring MT, not receiving fresh whole blood,
      and surviving at least 1 hour (reducing survival bias) were divided into 6-hour
      apheresis platelet (aPLT) transfusion ratio groups: LOW (aPLT:RBC, <=0.1, n =
      344) and HIGH (aPLT:RBC, >0.1, n = 70). Baseline characteristics of groups were
      compared. Factors influencing survival on univariate analysis were included in
      Cox proportional hazards models of 24-hour and 30-day survival. RESULTS: Patients
      received aPLT in the emergency department (4%), operating room (45%), intensive
      care unit (51%). The HIGH group presented with higher (p < 0.05) admission
      International Normalized Ratio (1.6 vs. 1.4), base deficit (8 vs. 7), and
      temperature (36.7 vs. 36.4). Overall mortality was 27%. At 24 hours, the HIGH
      group showed lower mortality (10.0% vs. 22.1%, p = 0.02). Absolute differences in
      30-day mortality were not significant (HIGH, 18.6%; LOW, 28.8%, p = 0.08). On
      adjusted analysis, the HIGH group was independently associated with increased
      survival: LOW group mortality hazard ratios were 4.1 at 24 hours and 2.3 at 30
      days compared with HIGH group (p = 0.03 for both). Increasing 6-hour FFP:RBC
      ratio was also independently associated with increased survival. CONCLUSION:
      Early (first 6 hours) hemostatic resuscitation incorporating platelets and plasma
      is associated with improved 24-hour and 30-day survival in combat casualties
      requiring MT.

PMID- 22847103
TI  - Therapeutic correction of thrombin generation in dilution-induced coagulopathy:
      computational analysis based on a data set of healthy subjects.
AB  - BACKGROUND: Prothrombin complex concentrates (PCCs), which contain different
      coagulation proteins, are attractive alternatives to the standard methods to
      treat dilution-induced (and, generally, traumatic) coagulopathy. We investigated
      the ability of a novel PCC composition to restore normal thrombin generation in
      diluted blood. The performance of the proposed PCC composition (coagulation
      factors [F] II, IX, and X and the anticoagulant antithrombin), designated PCC-AT,
      was compared with that of FVIIa and PCC-FVII, which is the PCC composition
      containing FII, FVII, FIX, and FX (main components of most PCCs). METHODS: We
      used a thoroughly validated computational model to simulate thrombin generation
      in normal and diluted blood for 472 healthy subjects in the control group of the
      Leiden Thrombophilia Study. For every simulated thrombin curve, we calculated and
      analyzed five standard thrombin generation parameters. RESULTS: The three
      therapeutic agents (FVIIa, PCC-FVII, and PCC-AT) caused statistically significant
      changes in each of the five thrombin generation parameters in diluted blood.
      Factor VIIa tended to primarily impact clotting time, thrombin peak time, and
      maximum slope of the thrombin curve, whereas in the case of PCC-FVII, thrombin
      peak height and the area under the thrombin curve were affected particularly
      strongly. As a result, these two therapeutics tended to push those respective
      parameters outside their normal ranges. PCC-AT significantly outperformed both
      FVIIa and PCC-FVII in its ability to normalize individual thrombin generation
      parameters in diluted blood. Furthermore, PCC-AT could simultaneously restore all
      five thrombin generation parameters to their normal levels in every subject in
      the study group. CONCLUSIONS: Our computational results suggest that PCC-AT may
      demonstrate a superior ability to restore normal thrombin generation compared
      with FVIIa and PCC-FVII.

PMID- 22847104
TI  - Into the matrix:  targeting fibroblasts in pulmonary fibrosis.
AB  - PURPOSE OF REVIEW: This review describes the challenges created by the existence
      of multiple molecular pathways leading to fibrosis and proposes that attention be
      focused on targeting the fibroblasts and myofibroblasts which themselves produce
      multiple cytokines and growth factors as well as the extracellular matrix, which
      is the hallmark of fibrotic lung disease. RECENT FINDINGS: The last 20 years have
      seen remarkable progress in our understanding of the molecular pathogenesis of
      pulmonary fibrosis leading to multiple programmes in drug discovery, and there
      are currently 15 actively recruiting trials registered on
      http://www.clinicaltrials.gov. Unfortunately, at this time only one new drug,
      pirfenidone, has progressed to approval for use in patients. Part of the
      frustration is that drugs that are effective in targeting inflammatory pathways
      have been ineffective in lung fibrosis. This may result from the inability to
      treat patients early in the disease process but it is also likely that pathways
      independent of inflammation can drive fibrosis. SUMMARY: We further propose that
      this approach should inhibit fibrosis independent of cell type or the signalling
      cascade that is activating these cells. We are hopeful that the next 20 years
      will see many more therapeutic options for patients suffering with fibrotic lung
      disease.

PMID- 22847106
TI  - Questioning the favorable influence of nerve identification during open inguinal
      herniorrhaphy is misleading and may increases the risk of surgeons' liability :
      Invited Commentary: "Does nerve identification during open inguinal herniorrhaphy
      reduce the risk of persistent pain?".

PMID- 22847107
TI  - Reanalysis of phosphoproteomics data uncovers ADP-ribosylation sites.

PMID- 22847105
TI  - Biomarkers in idiopathic pulmonary fibrosis.
AB  - PURPOSE OF REVIEW: This review examines the recent literature on molecular
      biomarkers of idiopathic pulmonary fibrosis (IPF). Specific attention is
      dedicated to the recent studies that identified the genes associated with IPF and
      the peripheral blood biomarkers that predict outcome in IPF. RECENT FINDINGS:
      Multiple studies attempted to identify diagnostic and predictive biomarkers in
      IPF. Until recently, these studies were limited in size and lacked replication,
      but still when taken together provided convincing evidence that changes in blood
      proteins (KL-6, SP-A, MMP-7, CCL-18, among others) or cells (fibrocytes and T
      cell subpopulations) are indicative of the disease presence and outcome. More
      recently, larger studies have identified gene polymorphisms associated with IPF,
      as well as protein markers and integrated clinical and molecular prediction rules
      that accurately predict outcome in patients with IPF. SUMMARY: The peripheral
      blood contains disease presence and outcome relevant information, and suggests
      distinct biologically defined outcome trajectories in patients with IPF. Although
      recently identified biomarkers should still be validated in multiple clinical
      contexts, there is sufficient evidence to suggest that collection of peripheral
      blood biomarkers needs to be incorporated in the design of drug studies and that
      some of these markers be clinically evaluated in lung transplant prioritization.

PMID- 22847108
TI  - CircadiOmics: integrating circadian genomics, transcriptomics, proteomics and
      metabolomics.

PMID- 22847109
TI  - jModelTest 2: more models, new heuristics and parallel computing.

PMID- 22847110
TI  - OpenFovea: open-source AFM data processing software.

PMID- 22847112
TI  - Connecting ecology and conservation through experiment.

PMID- 22847113
TI  - Structure-activity relationship study of WSS25 derivatives with anti-angiogenesis
      effects.
AB  - WGEW, an alpha(1-4) linked glucan with an alpha(1-4) linked branch attached to C
      6, was isolated from the rhizoma of Gastrodia elata Bl. WSS25, a sulfated
      derivative of WGEW, was reported to inhibit angiogenesis by disrupting
      BMP2/Smad/Id1 signaling pathway. However, the structure-activity relationship
      (SAR) for WSS25 is not known. To study the SAR, seven sulfated saccharides
      derived from WGEW degradation products, six sulfated polysaccharides with varying
      degrees of substitution, and four aminopropylated, carboxymethylated,
      phosphorylated, and acetylated derivatives of WGEW were prepared. A sulfated,
      unbranched product of polysaccharide was also obtained. The structural features
      of these derivatives were characterized by infrared spectroscopy and nuclear
      magnetic resonance spectroscopy. An HMEC-1 cell tube formation assay was employed
      to measure the antiangiogenic effect of the derivatives. The results indicated
      that only sulfated polysaccharides with molecular weights of more than 41,000 Da
      could inhibit HMEC-1 cell tube formation. The inhibition effect was dependent on
      the presence of a sulfate group, since the tube formation was not blocked by
      aminopropylated, carboxymethylated, phosphorylated, or acetylated WGEW. A higher
      degree of sulfate substitution on the polysaccharide led to a stronger inhibitory
      effect, and the degree of sulfate substitution between 0.173 and 0.194 was found
      to be optimal. Interestingly, the WGEW side chain was not required for anti-tube
      formation activity. All these preliminary results may provide a clue for further
      modification of the core structure of WSS25 to discover polysaccharide
      derivatives as novel anti-angiogenic inhibitors.

PMID- 22847115
TI  - Identification of neuronal loci involved with displays of affective aggression in
      NC900 mice.
AB  - Aggression is a complex behavior that is essential for survival. Of the various
      forms of aggression, impulsive violent displays without prior planning or
      deliberation are referred to as affective aggression. Affective aggression is
      thought to be caused by aberrant perceptions of, and consequent responses to,
      threat. Understanding the neuronal networks that regulate affective aggression is
      pivotal to development of novel approaches to treat chronic affective aggression.
      Here, we provide a detailed anatomical map of neuronal activity in the forebrain
      of two inbred lines of mice that were selected for low (NC100) and high (NC900)
      affective aggression. Attack behavior was induced in male NC900 mice by exposure
      to an unfamiliar male in a novel environment. Forebrain maps of c-Fos+ nuclei,
      which are surrogates for neuronal activity during behavior, were then generated
      and analyzed. NC100 males rarely exhibited affective aggression in response to
      the same stimulus, thus their forebrain c-Fos maps were utilized to identify
      unique patterns of neuronal activity in NC900s. Quantitative results indicated
      robust differences in the distribution patterns and densities of c-Fos+ nuclei in
      distinct thalamic, subthalamic, and amygdaloid nuclei, together with unique
      patterns of neuronal activity in the nucleus accumbens and the frontal cortices.
      Our findings implicate these areas as foci regulating differential behavioral
      responses to an unfamiliar male in NC900 mice when expressing affective
      aggression. Based on the highly conserved patterns of connections and
      organization of neuronal limbic structures from mice to humans, we speculate that
      neuronal activities in analogous networks may be disrupted in humans prone to
      maladaptive affective aggression. 

PMID- 22847116
TI  - Complications after plate fixation and elastic stable intramedullary nailing of
      dislocated midshaft clavicle fractures: a retrospective comparison.
AB  - PURPOSE: The incidence of operative treatment of dislocated midshaft clavicle
      fractures (DMCF) is rising due to unsatisfactory results after non-operative
      treatment. Knowledge of complications is important for selection of the surgical
      technique and preoperative patient counselling. The aim of this study is to
      compare complications after plate fixation and elastic stable intramedullary
      nailing (ESIN) with a titanium elastic nail (TEN) for DMCF. METHODS: A
      retrospective analysis of our surgical database was performed. From January 2005
      to January 2010, 90 patients with DMCF were treated with plate fixation or ESIN.
      Complications were evaluated in both treatment groups and subsequently compared.
      RESULTS: Seven implant failures occurred in six patients (14 %) of the plate
      group and one implant failure (2.1 %) was seen in the ESIN group (p = 0.051).
      Major revision surgery was performed in five cases in the plate group (11.6 %)
      and in one case (2.1 %) in the ESIN group (p = 0.100). Three refractures (7.0 %)
      were observed in the plate group after removal of the implant against none in the
      ESIN group (p = 0.105). Six minor revisions (13 %) were reported in the ESIN
      group and none were reported in the plate group (p = 0.027). CONCLUSIONS:
      Compared to other studies we report higher rates of refracture (7.0 %), major
      revision surgery (11.6 %) and implant failure (14.0 %) after plate fixation. The
      frequency of implant failures differed almost significantly for patients treated
      with plate fixation compared to ESIN. Furthermore, a tendency towards refracture
      after implant removal and major revision surgery after plate fixation was
      observed.

PMID- 22847117
TI  - Combined 33rd SICOT and 17th PAOA Orthopaedic World Conference.

PMID- 22847114
TI  - Osteopontin increases the expression of beta1, 4-galactosyltransferase-I and
      promotes adhesion in human RL95-2 cells.
AB  - Beta1, 4-Galactosyltransferase-I (beta1, 4-GalT-I), which transfers galactose
      from UDP-Gal to N-acetylglucosamine and N-acetylglucosamine-terminated
      oligosaccharides of N- and O-linked glycans in a beta(1-4) linkage, plays a
      critical role in cell adhesion, sperm-egg recognition, neurite growth, and tumor
      cell migration and invasion. Our previously experiments also show that beta1, 4
      GalT-I was up-regulated by estrogens and some important cytokines of embryo
      implantation especially Interleukin-1 (IL-1), TGF-alpha and Leukemia Inhibitory
      Factor (LIF) in endometrial cells. In the receptive phase human uterus,
      osteopontin (OPN) is the most highly up-regulated extracellular matrix/adhesion
      molecule/cytokine. In this study, we demonstrated the correlated expression of
      OPN and beta1, 4-GalT-I in endometrium during early pregnancy, and recombinant
      human OPN (rhOPN) protein induced the beta1, 4-GalT-I up-regulation in RL95-2
      cells. Inhibition of MEK/ERK, PI3K/AKT and NF-kappaB suppressed rhOPN-induced
      beta1, 4-GalT-I expression. In addition, rhOPN promoted the adhesion of
      blastocysts cells in vitro in beta1, 4-GalT-I-dependent manner. Moreover, the
      adhesion is greatly inhibited when beta1, 4-GalT-I was blocked with the specific
      antibody. Taken together, our data suggest that beta1, 4-GalT-I provides a
      mechanism to bridge embryo to endometrium during implantation.

PMID- 22847118
TI  - Achieving locked intramedullary fixation of long bone fractures: technology for
      the developing world.
AB  - Eighty per cent of severe fractures occur in developing countries. Long bone
      fractures are treated by conservative methods if proper implants, intraoperative
      imaging and consistent electricity are lacking. These conservative treatments
      often result in lifelong disability. Locked intramedullary nailing is the
      standard of care for long bone fractures in the developed world. The Surgical
      Implant Generation Network (SIGN) has developed technology that allows all
      orthopaedic surgeons to treat fracture patients with locked intramedullary
      nailing without the need for image intensifiers, fracture tables or power
      reaming. Introduced in 1999, SIGN nails have been used to treat more than 100,000
      patients in over 55 developing world countries. SIGN instruments and implants are
      donated to hospitals with the stipulation that they will be used to treat the
      poor at no cost. Studies have shown that patients return to function more
      rapidly, hospital stays are reduced, infection rates are low and clinical
      outcomes excellent. Cost-effectiveness analysis has confirmed that the system not
      only provides better outcomes, but does so at a reduced cost. SIGN continues to
      develop new technologies, in an effort to transform lives and bring equality in
      fracture care to the poorest of regions.

PMID- 22847120
TI  - Tumor proximity to the recurrent laryngeal nerve in patients with primary
      hyperparathyroidism undergoing parathyroidectomy.
AB  - BACKGROUND: Recurrent laryngeal nerve (RLN) injury is a rare complication for
      patients undergoing neck exploration for primary hyperparathyroidism (pHPT).
      Distances between RLNs and parathyroid adenomas have not been previously
      published. In this study we used a RLN monitor to identify the RLN and to measure
      the proximity to parathyroid tumors. METHODS: Patients with pHPT (n = 136)
      underwent neck exploration and had the clinical data recorded prospectively.
      Adenomas were recorded in 1 of 4 locations (right upper, right lower, left upper,
      left lower). Measurement of RLN to adenoma distances were recorded
      intraoperatively with the gland in situ. The RLN location was confirmed with a
      RLN monitor. RESULTS: The average RLN to adenoma distance was 0.52 +/- 0.52 cm.
      Adenomas in the right upper position were significantly closer to the nerve (0.25
      +/- 0.39 cm) compared with adenomas in the left upper (0.48 +/- 0.61 cm, p =
      .03), left lower (0.70 +/- 0.53 cm, p < .001), and right lower position (1.02 +/-
      0.56 cm, p < .001). Left upper adenomas were also significantly closer to the
      nerve compared with right lower adenomas (p < .001). Adenomas in the right upper
      position abutted the nerve more often (47 %) compared with adenomas in other
      positions (p = .001). There were no perioperative characteristics that predicted
      tumor abutment. There were no permanent RLN injuries. CONCLUSION: In patients
      with sporadic pHPT, parathyroid adenomas in the right upper location have, on
      average, greater proximity to the RLN and are more often directly abutting
      compared with adenomas in other locations.

PMID- 22847119
TI  - Intraoperative imprint cytology and frozen section pathology for margin
      assessment in breast conservation surgery: a systematic review.
AB  - BACKGROUND: Achieving negative surgical margins is critical to minimizing the
      risk of tumor recurrence in patients undergoing breast conservation surgery (BCS)
      for a breast malignancy. Our objective was to perform a systematic review
      comparing reexcision rates, sensitivity and specificity of the intraoperative use
      of the margin assessment techniques of imprint cytology (IC) and frozen section
      analysis (FSA), against permanent histopathologic section (PS). METHODS: The
      databases PubMed, Web of Knowledge, Cochrane Library and CINAHL Plus were
      searched for literature published from 1997 to 2011. Original investigations of
      patients who underwent BCS for breast cancer that evaluated margin assessment
      with PS and/or IC or FSA were included. Of 182 titles identified, 41 patient
      cohorts from 37 articles met inclusion criteria: PS (n = 19), IC (n = 7) and FSA
      (n = 15). Studies were summarized qualitatively using the Strengthening the
      Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort
      studies and the Strength of Recommendation Taxonomy (SORT) numerical scale for
      diagnostic studies. RESULTS: The final reexcision rates after primary BCS were 35
      % for PS, 11 % for IC (p = 0.001 vs. PS) and 10 % for FSA (p < 0.0001 vs. PS).
      For IC, reexcision rates decreased from 26 to 4 % (p = 0.18) and for FSA,
      reexcision rates decreased from 27 to 6 % (p < 0.0001). The pooled sensitivity of
      IC and FSA were 72 and 83 %. The pooled specificity of IC and FSA were 97 and 95
      %. The average length of each technique was 13 min for IC and 27 min for FSA.
      CONCLUSIONS: Patients who underwent BCS with intraoperative IC or FSA to assess
      negative surgical margins had significantly fewer secondary surgical procedures
      for excision of their breast malignancies.

PMID- 22847121
TI  - Does the rapid acceptance of ACOSOG Z0011 compromise selection of systemic
      therapy?

PMID- 22847122
TI  - Y-V oncoplastic wound repair of mastectomy dog-ear deformity.
AB  - The video demonstrates the surgical technique for correcting dog-ear deformity
      resulting from a mastectomy wound. This technique is applicable for both medial
      and lateral deformities.

PMID- 22847123
TI  - American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon
      practice patterns.
AB  - INTRODUCTION: The ACOSOG Z0011 trial has been described as practice-changing. The
      goal of this study was to determine the impact of the trial on surgeon practice
      patterns at our institution. METHODS: This is a review of practice patterns
      comparing the year before release of Z0011 to the year after an institutional
      multidisciplinary meeting discussing the results. Patients meeting Z0011
      inclusion criteria were identified. Clinicopathologic data were compared between
      the cohorts. RESULTS: There were 658 patients with clinical T1-2 tumors planned
      for breast conservation: 335 in the pre-Z0011 cohort and 323 post-Z0011. Sixty
      two (19 %) patients were sentinel lymph node (SLN) positive in the pre-Z0011
      group versus 42 (13 %) post-Z0011 (p = 0.06). Before Z0011, 85 % (53/62) of SLN
      positive patients underwent axillary node dissection (ALND) versus 24 % (10/42)
      after Z0011 (p < 0.001). After Z0011, surgeons were more likely to perform ALND
      on patients with larger tumors (2.2 vs. 1.5 cm, p = 0.09), lobular histology (p =
      0.01), fewer SLNs (1 vs. 3, p = 0.09), larger SLN metastasis size (4 vs. 2.5 mm,
      p = 0.19), extranodal extension present (20 vs. 6 %, p = 0.16), or a higher
      probability of positive non-SLNs (p = 0.03). Surgeons were less likely to perform
      intraoperative nodal assessment post-Z0011 (26 vs. 69 %, p < 0.001) resulting in
      decreased median operative times for SLN-negative patients (79 vs. 92 min, p <
      0.001). CONCLUSIONS: Surgeons at our institution have implemented Z0011 results
      for the majority of patients; however, clinicopathologic factors still impact the
      decision to perform ALND. Z0011 results have significantly impacted practice by
      decreasing rates of ALND, use of intraoperative nodal evaluation, and operative
      times.

PMID- 22847124
TI  - Long-term follow-up of lobular neoplasia (atypical lobular hyperplasia/lobular
      carcinoma in situ) diagnosed on core needle biopsy.
AB  - BACKGROUND: Lobular neoplasia (LN) includes atypical lobular hyperplasia (ALH)
      and lobular carcinoma in situ (LCIS). LN often is an incidental finding on breast
      core needle biopsy (CNBx) and management remains controversial. Our objective was
      to define the incidence of malignancy in women diagnosed with pure LN on CNBx,
      and identify a subset of patients that may be observed. METHODS: Patients
      diagnosed with LN on CNB between January 1993 and December 2010 were identified.
      Patients with an associated high-risk lesion or ipsilateral malignancy at time of
      diagnosis were excluded. All cases were reviewed by dedicated breast pathologists
      and breast imagers for pathologic classification and radiologic concordance,
      respectively. RESULTS: The study cohort was comprised of 184 (1.3 %) cases of
      pure LN (147 ALH, 37 LCIS) from 180 patients. Pathologic-radiologic concordance
      was achieved in 171 (93 %) cases. Excision was performed in 101 (55 %) cases and
      83 (45 %) were observed. Mean follow-up was 50.3 (range, 6-212) months. Of cases
      excised, 1 of 81 (1.2 %) ALH and 1 of 20 (5 %) LCIS cases were upstaged to ductal
      carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), respectively. Only
      1 of 101 (1 %) concordant lesions was upstaged on excision. Of the cases
      observed, 4 of 65 (6.2 %) developed ipsilateral cancer during follow-up: 1 of 51
      (2 %) case of ALH and 3 of 14 (21.4 %) cases with LCIS (2 ILC, 2 DCIS). During
      follow-up, 2.9 % (4/138) patients with excised or observed LN developed a
      contralateral cancer. CONCLUSIONS: These data support that not all patients with
      LN diagnosed on CNB require surgical excision. Patients with pure ALH,
      demonstrating radiologic-pathologic concordance, may be safely observed.

PMID- 22847125
TI  - Aldehyde dehydrogenase 1 expression is associated with poor prognosis in patients
      with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers
      in several solid tumors. However, few studies have examined the relationships
      between ALDH1 expression and the prognosis and clinical characteristics of
      esophageal squamous cell carcinoma (ESCC). METHODS: This study was a
      retrospective case-control study and included 152 patients with ESCC. A total of
      56 patients underwent surgery (OP group), 40 patients received neoadjuvant
      chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose
      cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients
      received initial systemic DFP therapy (CT group). The ALDH1 and CD44
      immunohistochemical expression levels of each tumor were evaluated and compared
      with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In
      the OP and NAC groups, multivariate analysis found that ALDH1 was independently
      associated with postoperative recurrence and prognosis (OP group, P=0.004 and
      0.016, respectively; NAC group, P=0.026 and 0.014, respectively). In addition,
      CD44 was found to be associated with postoperative recurrence in the OP group and
      prognosis in the NAC group (P=0.024 and 0.047, respectively). Among the ALDH1
      negative clinical stage II/III patients, the OP and NAC groups displayed better
      prognoses than the CT group (P<0.001). However, among the ALDH1-positive clinical
      stage II/III patients, the OP and NAC groups displayed poorer prognoses than the
      CT group (P=0.049). CONCLUSIONS: ALDH1 was found to be a predictor of
      postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of
      recurrence and prognosis. ALDH1 expression might affect the treatment strategy
      for ESCC.

PMID- 22847126
TI  - The significance of lobular carcinoma in situ and atypical lobular hyperplasia of
      the breast.
AB  - BACKGROUND: The significance of lobular neoplasia (LN), lobular carcinoma in situ
      (LCIS) and atypical lobular hyperplasia (ALH)) found at core needle biopsy (CNB)
      of the breast remains uncertain. There is a consistent risk of underestimating
      malignancy after the diagnosis of LN on CNB. The aim of this study was to
      determine if patients with a CNB result of LN need surgical excision. METHODS:
      Patients were identified by searching the institutions pathology database for the
      terms "lobular carcinoma in situ" and "atypical lobular hyperplasia" over 20
      years. Excluded from this study were those with core needle biopsy (CNB) results
      of ductal carcinoma in situ, atypical ductal hyperplasia, radial scar, or
      papilloma. Upgrade was defined as final surgical pathology of invasive carcinoma
      and/or ductal carcinoma in situ that was directly correlated to the site of the
      initial biopsy containing LN. RESULTS: LN was found at CNB in 285 patients, and
      71 % (n = 201) had subsequent surgical excisions. All patients with pleomorphic
      LCIS (pLCIS) underwent surgical excision. Following patients with pLCIS, patients
      with the diagnosis of LCIS were most likely to undergo surgical excision (80 %).
      Final pathology of the surgically excised specimens confirmed LN in 72 % (n =
      144). Also, 13 % (n = 26) of the operated patients were upgraded to malignancy,
      including 8 % of ALH and 19 % of LCIS cases. CONCLUSION: This is the largest
      series of surgical excisional pathology following LN on CNB ever reported. The
      likelihood of finding malignancy at surgical excision after CNB showing LN was 13
      %. Patients with the diagnosis of LN on CNB should be considered for surgical
      excision.

PMID- 22847127
TI  - Detailed pathologic characteristics of the primary colorectal tumor independently
      predict outcome after hepatectomy for metastases.
AB  - INTRODUCTION: Outcome after hepatic resection for colorectal cancer liver
      metastases (CRLM) is heterogeneous and accurate predictors of survival are
      lacking. This study analyzes the prognostic relevance of pathologic details of
      the primary colorectal tumor in patients undergoing hepatic resection for CRLM.
      METHODS: Retrospective review of a prospective database identified patients who
      underwent resection for CRLM. Clinicopathological variables were investigated and
      their association with outcome was analyzed. RESULTS: From 1997-2007, 1,004
      patients underwent hepatic resection for CRLM. The median follow-up was 59 months
      with a 5-year survival of 47%. Univariate analysis identified nine factors
      associated with poor survival; three of these related to the primary tumor:
      lymphovascular invasion (LVI, p<0.0001), perineural invasion (p=0.005), and
      degree of regional lymph node involvement (N0 vs. N1 vs. N2, p<0.0001).
      Multivariate analysis identified seven factors associated with poor survival, two
      of which related to the primary tumor: LVI (hazard ratio (HR) 1.3, 95% confidence
      interval (CI) 1.06-1.64, p=0.01) and degree of regional lymph node involvement
      [N1 (HR 1.3, 95% CI 1.04-1.69, p=0.02) vs. N2 (HR 1.7, 95% CI 1.27-2.21,
      p<0.0005)]. A significant decrease in survival along the spectrum of patients
      ranging from LVI negative/N0 to LVI positive/N2 was present. Patients who were
      LVI-positive/N2 had a median survival of 40 months compared with 74 months for
      patients who were LVI-negative/NO (p<0.0001). CONCLUSIONS: Histopathologic
      details of the primary colorectal tumor, particularly LVI and the detailed
      assessment of the degree of lymph node involvement, are strong predictors of
      survival. Future biomarker studies should consider exploring factors related to
      the primary colorectal tumor.

PMID- 22847128
TI  - Editorial: sentinel node biopsy for breast cancer: past, present, and future.

PMID- 22847129
TI  - Further thoughts on authorship: gift authorship.

PMID- 22847131
TI  - Comparative effects of gamma and electron beam irradiation on the antioxidant
      potential of Portuguese chestnuts (Castanea sativa Mill.).
AB  - Chestnuts (Castanea sativa Mill.) are widely consumed all over the world, and
      have been recently studied for their antioxidant potential. The present study
      reports the effect of e-beam and gamma radiation (doses of 0, 0.5, 1 and 3 kGy)
      on the antioxidant potential of Portuguese chestnuts. Irradiation might be an
      alternative preservation method, since Methyl Bromide, a widely used fumigant,
      was banished by the European Union in 2010 due to its toxicity. The antioxidant
      activity was evaluated through 2,2-diphenyl-1-pycrylhydrazyl (DPPH) free radical
      scavenging activity assay, reducing power by the Ferricyanide/Prussian blue
      assay, and lipid peroxidation inhibition by beta-carotene/linoleate and
      thiobarbituric acid reactive substances (TBARS) assays. The analysis of total
      phenolics and flavonoids was performed by spectrophotometric assays. Irradiated
      samples preserved total phenolics content (but not flavonoids) and revealed
      higher antioxidant activity (lower EC50 values) than the control samples. The
      most indicated doses to maintain antioxidants content, and to increase
      antioxidant activity were 1 and 3 kGy for electron beam and gamma radiation,
      respectively.

PMID- 22847130
TI  - Suicide attempt and suicidal ideation and their associations with demographic and
      clinical correlates and quality of life in Chinese schizophrenia patients.
AB  - OBJECTIVES: This study aimed to examine the prevalence and correlates of lifetime
      suicide attempts and current suicidal ideation in community-dwelling
      schizophrenia patients in China. METHOD: A sample of 540 schizophrenia patients
      was randomly selected in Beijing, China. All subjects were interviewed using
      standardized assessment instruments and their basic socio-demographic and
      clinical data including history of suicide attempts were collected. RESULTS: The
      prevalence of lifetime suicide attempts and the point prevalence of suicidal
      ideation were 12.0%, and 21.1%, respectively. In multiple logistic regression
      analyses, the presence of lifetime suicide attempt was independently associated
      with rural residence, having major medical conditions and better social
      functioning, while higher likelihood of current suicidal ideation was associated
      with past suicide attempt, the severity of overall psychopathology and depressive
      symptoms and lower psychological quality of life (QOL). CONCLUSION: Among Chinese
      outpatients with schizophrenia, increased current symptoms and poorer QOL were
      correlated with current suicidal ideation, while demographic factors and
      indicators of greater social support were mostly correlated with lifetime suicide
      attempts. This study may help to identify important subgroups of patients with
      schizophrenia at particularly high risk of suicidal behavior.

PMID- 22847132
TI  - Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and
      their cytotoxicity in NRK-52E rat kidney cells.
AB  - The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1
      monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in
      Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney
      cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined
      2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate
      dose-dependently decreased the mean body weight, and caused significant increase
      of serum urea nitrogen and creatinine in dead mice compared to the control and
      survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate
      were renal tubular necrosis, protein casts and spermatids decrease in the
      seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50
      value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW.
      Obvious changes were not observed on mean body weight, absolute and relative
      organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD
      dipalmitate. However, renal tubular necrosis, protein casts and spermatids
      decrease were also observed in the dead mice. In addition, MTT and LDH assay
      results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat
      kidney cells in a dose-dependent manner. Together, the results indicated a
      greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate.

PMID- 22847133
TI  - Evaluation of nephrotoxic effects of mycotoxins, citrinin and patulin, on
      zebrafish (Danio rerio) embryos.
AB  - Citrinin (CTN) and patulin (PAT) are fungal secondary metabolites which are found
      in food and feed and showed organotoxicity in mature animals. In this study
      zebrafish embryos were applied to investigate the developmental toxicity of CTN
      and PAT on embryonic kidney. In the presence of CTN and PAT, the gross morphology
      of kidneys from embryos with green fluorescent kidney (wt1b:GFP) was not
      apparently altered. Histological analysis of CTN-treated embryos indicated cystic
      glomerular and tubular lesions; a disorganized arrangement of renal cells was
      also found in the PAT-treated group. From the view point of renal function,
      dextran clearance abilities of embryos exposed to CTN and PAT were significantly
      reduced. The damaged renal function caused by CTN could be partially rescued by
      the administration of pentoxifylline, suggesting the reduction of glomerular
      blood flow contributes to CTN-induced renal dysfunction. Additionally, CTN
      induced the expression of proinflammation genes, including COX2a, TNF-alpha and
      IL-1beta, but failed to modify the levels and distribution of wt1a transcript and
      Na(+)/K(+)-ATPase protein. In summary, CTN and PAT caused profound nephrotoxicity
      in histological structure and biological function of zebrafish embryos; the
      inflammatory pathway and blood rheology may involve in CTN-induced renal
      impairment.

PMID- 22847134
TI  - Ways and criteria to develop valid study designs and to identify markers to
      explore the effects of diets on health were further identified in the PASSCLAIM
      project. Foreword.

PMID- 22847135
TI  - Naringin induces death receptor and mitochondria-mediated apoptosis in human
      cervical cancer (SiHa) cells.
AB  - Cervical cancer is the second most common female cancer worldwide, and it remains
      a challenge to manage preinvasive and invasive lesions. Fruit-based cancer
      prevention entities, such as flavonoid and their derivatives, have demonstrated a
      marked ability to inhibit preclinical models of epithelial cancer cell growth and
      tumor formation. Here, we extend the role of naringin-mediated chemoprevention to
      that of cervical carcinogenesis. The present study sought to investigate the
      therapeutic potential effect of naringin on apoptosis in human cervical SiHa
      cancer cells. Viability of SiHa cells was evaluated by the MTT assay, apoptosis
      and mitochondrial transmembrane potential by flow cytometry, and pro-apoptotic
      related genes by Real-time quantitative PCR. Naringin showed a 50% inhibition of
      SiHa human cervical cancer cells at a concentration of 750MUM. SiHa cells
      exhibited apoptotic cell death, intranucleosomal DNA fragmentation, morphological
      changes and decline in the mitochondrial transmembrane potential. In addition,
      administration of naringin increased the expression of caspases, p53 and Bax, Fas
      death receptor and its adaptor protein FADD. These results suggest that the
      induction of apoptosis by naringin is through both death-receptor and
      mitochondrial pathways. Taken together, our results suggest that naringin might
      be an effective agent to treat human cervical cancer.

PMID- 22847136
TI  - Phenethyl isothiocyanate-induced cytoskeletal changes and cell death in lung
      cancer cells.
AB  - Isothiocyanates are known for their anticarcinogenic and antitumor potential,
      however, the exact mechanism of their action has not been fully elucidated. The
      present study was designed to investigate and compare the effects of phenethyl
      isothiocyanate on cell morphology, the cytoskeleton and induction of cell death
      in human non-small cell lung cancer cell lines A549 and H1299 differing in p53
      status. Cell viability tests (MTT assay, xCELLigence system) showed that PEITC
      exhibits lower cytotoxicity to A549 cells containing wild-type p53. The observed
      growth-inhibitory effect of PEITC was dose-dependent, but time-dependence was
      observed only at higher concentrations. The results of flow-cytometric and
      fluorescence-microscopic analyses indicate that PEITC induced disassembly of
      actin stress fibers and degradation of tubulin which, most likely, contributed to
      the induction of cell death. Although, 24-h incubation caused G2/M cell cycle
      arrest, the fraction of G2/M cells decreased in a dose- and time-dependent manner
      in favor of cells with sub-G1 DNA content. Further experiments (Annexin V
      staining, electron microscopic observations) confirmed that the apoptosis
      inducing potency of PEITC is probably the main factor responsible for cell growth
      inhibition. However, PEITC treatment also resulted in the appearance of an
      increased proportion of H1299 cells exhibiting morphological features of mitotic
      catastrophe.

PMID- 22847137
TI  - Arecoline inhibits myogenic differentiation of C2C12 myoblasts by reducing STAT3
      phosphorylation.
AB  - Areca nut (Areca catechu) is chewed regularly as a medical and psychoactive food
      by about 10% of the world population, in countries including India, Taiwan and
      parts of Southern Asia. Areca nut chewing during pregnancy has been associated
      with both lower birth weight and premature birth. Animals of low birth weights
      showed retardation of muscle development. Our previous study showed that
      arecoline, the major areca alkaloid, decreased the number of implanted embryos.
      Here we sought to determine the effects of arecoline in myogenic differentiation
      by in vitro assays using C2C12 myoblast cells. The results showed that arecoline
      higher than 0.4mM significantly increased apoptosis and decreased viability of
      C2C12 cells. Morphometric measurements of myotube formation and analyses of
      myogenic markers, myosin heavy chain and myogenin, revealed that myogenic
      differentiation was inhibited by 0.04-0.08 mM arecoline. Moreover, phosphorylated
      but not total STAT3 was significantly inhibited by arecoline during myotube
      formation. These results indicate that arecoline inhibits the myogenic
      differentiation of C2C12 cells by reducing the activation of STAT3, an upstream
      regulator of myogenesis. Improved understanding of the effects of arecoline
      during myogenic differentiation may help to establish public health policies and
      to develop potential treatments for such patients.

PMID- 22847138
TI  - Genotoxic and mutagenic effects of erythrosine B, a xanthene food dye, on HepG2
      cells.
AB  - Erythrosine (ErB) is a xanthene and an US Food and Drug Administration approved
      dye used in foods, drugs and cosmetics. Although its utilization is permitted,
      ErB is described as inhibitor of enzymes and protein-protein interactions and is
      toxic to pituitary and spermatogenesis processes. However, the genotoxicity and
      mutagenicity of ErB is inconclusive in the literature. This study aimed to
      analyze the genotoxicity of this dye using the alkaline comet assay and is the
      first investigation to evaluate ErB mutagenicity using the cytokinesis block
      micronucleus cytome (CBMN-Cyt) assay in HepG2 cells. These cells were chosen
      because they produce phase I and phase II enzymes that can mimic in vivo
      metabolism. The cells were treated with seven concentrations (0.1-70.0 MUg mL(
      1)) of ErB, and the results showed genotoxicity at the two highest concentrations
      and mutagenicity at six concentrations. Furthermore, as micronuclei result from
      clastogenic and aneugenic processes, while comet assay is often considered more
      sensitive and detects DNA single strain breaks, we suggest that an aneugenic is
      responsible for the observed damage. Although ErB is approved for use in the
      food, cosmetic and pharmaceutical industries, it must be used carefully because
      it damages the DNA structure.

PMID- 22847139
TI  - Genotoxicity studies in the ST cross of the Drosophila wing spot test of
      sunflower and soybean oils before and after frying and boiling procedures.
AB  - Sunflower and soybean oils were tested for genotoxicity in the Drosophila wing
      somatic mutation and recombination assay. Results indicate that both oils produce
      genotoxic effects when tested without any previous frying or boiling processes.
      Boiling sunflower oil during fifteen, thirty and sixty minutes significantly
      increased its genotoxic response; nevertheless, after frying potatoes this oil
      showed a significant decrease in the genotoxic activity. On the other hand,
      boiling and frying soybean oil in the same conditions results in a decrease of
      its genotoxic potential. We have also detected that the amount of total polar
      materials increases significantly in oils submitted to frying or boiling process.
      Nevertheless, in oils obtained after frying potatoes, the amount of TPM was
      higher than after boiling. It is suggested that this effect is probably due to
      the amount of non-volatile TPM, the fatty acid composition of the oils, the types
      of frying oil, the high frying temperature and time, and the number of boiling
      and frying. This is the first study reporting genotoxicity data in Drosophila for
      the boiling and frying of both sunflower and soybean oils.

PMID- 22847140
TI  - A regional anesthesia-based "swing" operating room model reduces non-operative
      time in a mixed orthopedic inpatient/outpatient population.
AB  - PURPOSE: We recently reported on the efficacy of a new "swing" room model
      involving two alternating ORs and regional anesthesia in increasing operating
      room (OR) throughput in a dedicated ambulatory orthopedic surgery facility. The
      purpose of this study was to evaluate this model in a main OR suite setting with
      typical mixed inpatient/outpatient cases. METHODS: We conducted a retrospective
      matched-pair cohort study of 133 upper extremity surgery patients treated in the
      swing room model under ultrasound-guided brachial plexus blockade. We compared
      this cohort with case-matched historical controls treated in the traditional
      single OR model under general anesthesia. The primary endpoint was non-operative
      time, defined as the interval between skin closure and incision in the following
      case. Secondary endpoints included throughput estimated as the median number of
      cases per eight-hour day, postanesthesia care unit (PACU) bypass rates, and
      postoperative pain/nausea and vomiting (PONV) intervention rates. RESULTS:
      Compared with the control group, non-operative times in the swing room group were
      faster (swing: median 19 min; interquartile range [IQR 8-31] vs control: median
      57 min; IQR [49-65]; P < 0.0001). In the swing room model, the estimated daily
      throughput was 33% greater (swing: median 5.6 cases; IQR [5.0-6.2] vs control:
      median 4.2 cases; IQR [4.0-4.4]; P < 0.0001), and the PACU bypass rate was higher
      (swing: 60% vs control: 0%; P < 0.0001). Fewer patients received postoperative
      opioids (swing: 20% vs control: 82%; P < 0.0001) and treatment for PONV (swing:
      2% vs control: 20%; P < 0.0001) in the swing room model. CONCLUSION: The
      implementation of a "swing" room care model based on ultrasound-guided regional
      anesthesia in a typical mixed inpatient/outpatient population decreased non
      operative times, increased throughput, and improved recovery profiles compared
      with case-matched historical controls in the traditional model under general
      anesthesia.

PMID- 22847141
TI  - Chiral Zn(II)-bisamidine complex as a Lewis-Bronsted combined acid catalyst:
      application to asymmetric Mukaiyama aldol reactions of alpha-ketoesters.
AB  - Focusing on the steric and electronic properties of the resonance-stabilized
      amidine framework, a cationic metal-bisamidine complex was designed as a
      conjugated combined Lewis-Bronsted acid catalyst. The chiral Zn(II)-bisamidine
      catalyst prepared from the 2,2'-bipyridyl derived bisamidine ligand, ZnCl2, and
      AgSbF6 promoted asymmetric Mukaiyama aldol reaction of alpha-ketoester and
      alpha,alpha-disubstituted silyl enol ether to afford the alpha-hydroxyester
      having sequential quarternary carbons in good yield, albeit with low
      enantioselectivity. Addition of 1.0 equivalent of the fluoroalcohol having
      suitable acidity and bulkiness dramatically increased the enantioselectivity (up
      to 68% ee). DFT calculations suggested that this additive effect would be caused
      by self-assembly of the fluoroalcohol on the Zn(II)-bisamidine catalyst.

PMID- 22847142
TI  - Synthesis, antigenicity against human sera and structure-activity relationships
      of carbohydrate moieties from Toxocara larvae and their analogues.
AB  - Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing
      the Galbeta1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of
      the parasite Toxocara and their analogues have been accomplished. Trisaccharides
      Fuc2Mealpha1-2Gal4Mebeta1-3GalNAcalpha1-OR (A), Fucalpha1-2Gal4Mebeta1
      3GalNAcalpha1-OR (B), Fuc2Mealpha1-2Galbeta1-3GalNAcalpha1-OR (C), Fucalpha1
      2Galbeta1-3GalNAcalpha1-OR (D) and a disaccharide Fuc2Mealpha1-2Gal4Mebeta1-OR
      (E) (R = biotinylated probe) were synthesized by block synthesis using 5
      (methoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1-->3)-2
      azide-4-O-benzyl-2-deoxy-alpha-D-galactopyranoside as a common glycosyl acceptor.
      We examined the antigenicity of these five oligosaccharides by enzyme linked
      immunosorbent assay (ELISA). Our results demonstrate that the O-methyl groups in
      these oligosaccharides are important for their antigenicity and the biotinylated
      oligosaccharides A, B, C and E have high serodiagnostic potential to detect
      infections caused by Toxocara larvae.

PMID- 22847143
TI  - Acuminatol and other antioxidative resveratrol oligomers from the stem bark of
      Shorea acuminata.
AB  - A new resveratrol dimer, acuminatol (1), was isolated along with five known
      compounds from the acetone extract of the stem bark of Shorea acuminata. Their
      structures and stereochemistry were determined by spectroscopic methods, which
      included the extensive use of 2D NMR techniques. All isolated compounds were
      evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging activity (RSA) and the beta-carotene-linoleic acid
      (BCLA) assays, and compared with those of the standards of ascorbic acid (AscA)
      and butylated hydroxytoluene (BHT). All compounds tested exhibited good to
      moderate antioxidant activity in the DPPH assay (IC50s 0.84 to 10.06 mM) and
      displayed strong inhibition of beta-carotene oxidation (IC50s 0.10 to 0.22 mM).
      The isolated compounds were evaluated on the Vero cell line and were found to be
      non-cytotoxic with LC50 values between 161 to 830 uM.

PMID- 22847144
TI  - Synthesis and characterization of cationic glycidyl-based poly(aminoester)-folic
      acid targeting conjugates and study on gene delivery.
AB  - A new poly(aminoester) (EPAE-FA) containing folic acid and amino groups in the
      backbone and side chain was synthesized. EPAE-FA self-assembled readily with the
      plasmid DNA (pCMV-betagal) in HEPES buffer and was characterized by dynamic light
      scattering, zeta potential, fluorescence images, and XTT cell viability assays.
      To evaluate the transfection effect of graft ratio of FA on the EPAE system, EPAE
      FA polymers with two different graft ratios (EPAE-FA12k and EPAE-FA14k) were also
      prepared. This study found that all EPAE-FA polymers were able to bind plasmid
      DNA and yielded positively charged complexes with nano-sized particles (< 200
      nm). To assess the transfection efficiency mediated by EPAE and EPAE-FA polymers,
      we performed in vitro transfection activity assays using FR-negative (COS-7) and
      FR-positive (HeLa) cells. The EPAE-FA12k/DNA and EPAE-FA14k/DNA complexes were
      able to transfect HeLa cell in vitro with higher transfection efficiency than
      PEI25k/DNA at the similar weight ratio. These results demonstrated that the
      introduction of FA into EPAE system had a significant effect on transferring
      ability for FR-positive cells (HeLa). Examination of the cytotoxicity of PEI25k
      and EPAE-FA system revealed that EPAE-FA system had lower cytotoxicity. In this
      paper, EPAE-FA seemed to be a novel cationic poly(aminoester) for gene delivery
      and an interesting candidate for further study.

PMID- 22847145
TI  - Integrative Plant Biology. Preface.

PMID- 22847147
TI  - Ethical challenges of preexposure prophylaxis for HIV.

PMID- 22847148
TI  - A pass too far: dissociation of internal energy selected paracyclophane cations,
      theory and experiment.
AB  - The vacuum ultraviolet (VUV) photoionization and dissociative photoionization of
      three hydroxy-substituted [2.2]paracyclophane derivatives were studied yielding
      adiabatic ionization energies and dissociative photoionization energies
      (appearance energies). The simplest dissociation pathway is the breaking of both
      CH(2)-CH(2) bridge units and fragmenting the molecular ion in half to yield
      xylylene neutral and cationic fragments. The experimental data show that this
      process is outcompeted by a faster, higher energy channel, possibly yielding
      cyclooctatetraene derivatives. The role of the reaction coordinate, the effect of
      large amplitude motions on the density of states function at low and high
      energies and the temperature dependent 'population gap' in the internal energy
      distribution in large molecules are discussed in the context of applying
      statistical models to the dissociation. Computational approaches to the binding
      energy of paracyclophanes are marred with pitfalls. Noncovalent interactions play
      a major role in keeping paracyclophanes bound by some 200 kJ mol(-1) with respect
      to the two xylylene motifs, and the covalent CH(2)-CH(2) bonds are mostly
      counteracted by the geometric strain. The stabilizing effects are twofold: first,
      paracyclophanes are aromatic compounds, whereas xylylenes are not. Thus, the
      aromaticity of the molecule is induced by dimerization. Second, dispersive pi-pi
      interactions also stabilize the molecule. We evaluated 23 different computational
      chemistry approaches, and found that very few of the favorably scaling ones give
      an adequate description of this system. Among the DFT functionals tested, only
      PBE-D3 and perhaps M06-2X yielded consistently accurate results, comparable with
      MP3 and CCSD, or the G4 and CBS-QB3 composite methods. MP2 results in general
      suffer from significant overbonding.

PMID- 22847149
TI  - A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity
      predominance.
AB  - Whole-exome sequencing of two affected sibs and their mother who showed a unique
      quadriceps-dominant form of neurogenic muscular atrophy disclosed a heterozygous
      DYNC1H1 mutation [p.H306R (c.917A>G)]. The identical mutation was recently
      reported in a pedigree with the axonal form of Charcot-Marie-Tooth disease. Three
      other missense mutations in DYNC1H1 were also identified in families with
      dominant spinal muscular atrophy with lower extremity predominance. Their
      clinical features were consistent with those of our family. Our study has
      demonstrated that the same DYNC1H1 mutation could cause spinal muscular atrophy
      as well as distal neuropathy, indicating pleotropic effects of the mutation.

PMID- 22847150
TI  - Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation.
AB  - We identified the main features of Charcot-Marie-Tooth (CMT) disease, type 4F,
      caused by a periaxin gene (PRX) mutation in Japanese patients. Periaxin is known
      as one of the key myelination molecules, forming tight junction between myelin
      loop and axon. We collected 427 DNA samples from individuals with CMT or CMT
      related neuropathy, negative for PMP22 duplication. We investigated PRX mutations
      using a purpose-built resequencing array screen during the period 2006-2012. We
      detected two types of PRX mutations in three patients; one patient showed a novel
      homozygous p.D651N mutation and the other two showed homozygous p.R1070X
      mutation. All PRX mutations reported so far have been of nonsense or frameshift
      type. In this study, we found homozygous missense mutation p.D651N. Aspartate 651
      is located in a repeat domain; its position might indicate an important function.
      PRX mutations usually lead to early-onset, autosomal-recessive demyelinating CMT
      neuropathy 4F (CMT4F) or Dejerine-Sottas disease; their clinical phenotypes are
      severe. In our three patients, the onset of the disease was at the age of 27
      years or later, and their clinical phenotypes were milder compared with those
      reported in previous studies. We showed a variation of clinical phenotypes for
      CMT4F caused by a novel, nonsense PRX mutation.

PMID- 22847151
TI  - Platelet activation and platelet-leukocyte interaction in beta
      thalassemia/hemoglobin E patients with marked nucleated erythrocytosis.
AB  - Patients with thalassemia, an inherited hemolytic anemia, have increased risk of
      hypercoagulable complications. A whole blood flow cytometric (FCM) method has
      been used for studies of platelet activation and platelet-leukocyte aggregation
      in these patients. However, this FCM method presents technical difficulties
      because of the high proportion of immature red blood cells (RBCs) in these
      patients. A protocol for the simultaneous measurement of platelet activation and
      their aggregation with leukocyte populations in whole blood using four-color FCM
      which excluded immature RBC was devised, and evaluated for the evaluation of
      platelet function in patients with beta-thalassemia/hemoglobin E (HbE). Whole
      blood from these patients and from healthy volunteers was stained for platelet
      activation and platelet-leukocyte aggregates using anti-CD42a, anti-CD62P, anti
      CD45 and glycophorin A (GPA) conjugated with different fluorochromes. Our FCM
      method is simple, effective and based on the assumption that GPA is present on
      all immature RBCs, but is not expressed on CD45+ leukocytes. Results from the
      studies showed that blood samples from these patients contained a high frequency
      of circulating activated platelets (CD42a+/CD62P+) when compared to samples from
      healthy individuals. The percentage of platelet-neutrophil, platelet-monocyte-but
      not platelet-lymphocyte-aggregates were also elevated in both thalassemia
      genotypes with marked increase in patients who had undergone splenectomy. These
      findings suggest that platelets adhere to neutrophils and monocytes are activated
      which support the clinical observation that splenectomized thalassemia patients
      have an increased risk of arterial or venous thrombotic manifestations.

PMID- 22847152
TI  - NT-pro-BNP: not the prognostic all-rounder in elderly patients undergoing
      allogeneic stem cell transplantation.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is a curative approach for
      several diseases predominantly affecting elderly patients. Overall survival is
      compromised by treatment-related mortality (TRM), GvHD, and relapse.
      Pretransplant clinical risk indicators in elderly patients qualifying for HCT are
      highly desirable. Pro-BNP is known as a predictor of death in patients with an
      increasing variety of clinical conditions and frequently used as a routine
      parameter for organ complications in the allogeneic transplant setting without
      well-established scientific evidence. Our hypothesis was that pre-HCT NT-pro-BNP
      could aid in identifying elderly patients at risk for early mortality. We
      retrospectively evaluated NT-pro-BNP values in 177 consecutive patients of >=60
      years HCT (2005-2010). In 29.4 % of cases, NT-pro-BNP values were within our
      institute's normal range (<125 pg/ml). Analysis of different NT-pro-BNP cutoff
      points by receiver operating characteristics curve for mortality at day +100
      revealed no single cutoff value with satisfying specificity and sensitivity. The
      individual outcome of patients with extremely high NT-pro-BNP values was not
      associated with an increase in mortality or cardiovascular morbidity. NT-pro-BNP
      values of patients succumbing to TRM did not differ significantly from those
      alive or having died of relapse-median 276 vs. 217 pg/ml. In conclusion, pre-HCT
      NT-pro-BNP was of no convincing prognostic relevance for day 100 mortality.

PMID- 22847153
TI  - Application of a new microcantilever biosensor resonating at the air-liquid
      interface for direct insulin detection and continuous monitoring of enzymatic
      reactions.
AB  - Here we describe the application of a recently developed high-resolution
      microcantilever biosensor resonating at the air-liquid interface for the
      continuous detection of antigen-antibody and enzyme-substrate interactions. The
      cantilever at the air-liquid interface demonstrated 50% higher quality factor and
      a 5.7-fold increase in signal-to-noise-ratio (SNR) compared with one immersed in
      the purified water. First, a label-free detection of a low molecular weight
      protein (insulin, 5.8 kDa) in physiological concentration was demonstrated. The
      liquid facing side of the cantilever was functionalized by coating its surface
      with insulin antibodies, while the opposite side was exposed to air. The meniscus
      membrane at the micro-slit around the cantilever sustained the liquid in the
      microchannel. After optimizing the process of surface functionalization, the
      resonance frequency shift was successfully measured for insulin solutions of 0.4,
      2.0, and 6.3 ng ml(-1). To demonstrate additional application of the device for
      monitoring enzymatic protein degradation, the liquid facing microcantilever
      surface was coated with human recombinant SOD1 (superoxide dismutase 1) and
      exposed to various concentrations of proteinase K solution, and the kinetics of
      the SOD1 digestion was continuously monitored. The results showed that it is a
      suitable tool for sensitive protein detection and analysis.

PMID- 22847154
TI  - Challenges to implementing patient-centered research.

PMID- 22847155
TI  - A five-marker panel in a multiplex PCR accurately detects microsatellite
      instability-high colorectal tumors without control DNA.
AB  - Microsatellite instability (MSI) testing is used to screen for Lynch syndrome.
      The current technique for MSI determination requires DNA from normal and
      neoplastic tissue and is expensive and laborious. Five quasi-monomorphic markers
      (NR-21, BAT-25, MONO-27, NR-24, and BAT-26) are included in the Promega MSI
      analysis kit. With the working hypothesis that this 5-marker panel can accurately
      determine the MSI status of colorectal tumors without using paired control DNA,
      we evaluated 478 colorectal tumors and divided them into a test group (N=172,
      colorectal adenocarcinomas) and a validation group (N=306 including 179
      colorectal adenocarcinomas and 127 adenomas). The quasi-monomorphic variation
      range of each marker was generated from the test group (172 normal samples) and
      used as a reference value in the subsequent interpretation of MSI status in the
      test and validation groups. Considering the MSI result using a 5-marker panel
      with paired control DNA as the gold standard, we identified 136 microsatellite
      stable (MSS) and 36 microsatellite instability-high (MSI-H) colorectal tumors in
      the test group and 259 MSS and 47 MSI-H colorectal tumors in the validation
      group. Using the quasi-monomorphic variation range of each marker rather than
      paired normal DNA, the 5-marker panel identified all MSI-H colorectal tumors in
      the test and validation groups, when MSI-H was defined as >=2 unstable markers.
      Our study demonstrates that the 5-marker panel within a multiplex polymerase
      chain reaction of the Promega MSI analysis kit accurately identifies all MSI-H
      and 95.2% MSS colorectal tumors without using paired normal DNA.

PMID- 22847156
TI  - 11q21 rearrangement is a frequent and highly specific genetic alteration in
      mucoepidermoid carcinoma.
AB  - Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor.
      Translocation t(11;19)(q21;p13) involving the MECT1 and MAML2 genes has been
      suggested as a diagnostic marker in these tumors. To determine the specificity of
      11q21 locus rearrangements for MEC, fluorescence in situ hybridization analysis
      with specific MEC-I Dual Color Break Apart Probe was performed on a tissue
      microarray containing samples from almost 1200 salivary gland adenomas and
      carcinomas. Rearrangements of 11q21 were observed in 40% of 217 MECs. The
      frequency of rearrangements decreased with tumor grade and was found in 53% of
      G1, 43% of G2, and 31% of G3 tumors (P=0.015). There were no 11q21 rearrangements
      found in other salivary gland carcinomas including 142 adenoid cystic carcinomas,
      104 acinic cell adenocarcinomas, 76 adenocarcinoma not otherwise specified, 38
      epithelial-myoepithelial carcinomas, 15 polymorphous low-grade adenocarcinomas,
      18 basal cell adenocarcinomas, 19 myoepithelial carcinomas, 12 papillary
      cystadenocarcinomas, 6 salivary duct carcinomas, and 10 oncocytic carcinomas.
      Furthermore, all analyzed salivary gland adenomas, including 39 cases of Warthin
      tumor and control samples, either from the salivary gland or from other organs
      were negative for 11q21 rearrangements. It is concluded that MECT1-MAML2 gene
      fusion is a highly specific genetic alteration in MEC with predominance in low
      grade and intermediate-grade tumors.

PMID- 22847157
TI  - Detection of EGFR mutation in tissue samples of non-small-cell lung cancer by a
      fluorescence polarization assay.
AB  - It is important to identify epidermal growth factor receptor (EGFR) mutations,
      which have a good value for the individualized management of patients with non
      small-cell lung cancer. A novel method for detecting the mutations on exons 19,
      21 of EGFR in primary carcinoma samples by a fluorescence polarization (FP) assay
      was developed in this research. Firstly, 2 pairs of general primers of exons 19,
      21 of EGFR were, respectively, used to amplify the target regions in each exon in
      2 reactions. Then, 2 probes specific for wild or mutation exons 19, 21 of EGFR
      were labeled with tetramethyl 6-carboxyrhodamine or 6-carboxyfluorescein
      hybridized, respectively, with their target amplicons, and the hybridization
      resulted in an increase in the FP values. Exon 19 deletion and exon 21 missense
      mutation were determined by the analysis of the FP values. EGFR mutations in 372
      non-small-cell lung cancer samples were analyzed in parallel with an FP assay and
      a sequencing assay. There was no significant difference between the mutation
      status results obtained with the FP assay and the results obtained with the
      sequencing assay. The minimum detection level established with this assay was 40
      copies/uL. Reliable results could be obtained when more than 30 ng of DNA was
      tested by a FP assay. An FP assay was able to detect the mutation DNA of EGFR
      even when its content was as low as 10%. An FP assay allowed the semiautomated
      detection of EGFR mutations in solution, and it was much simpler and cost
      effective than the traditional methods.

PMID- 22847158
TI  - CIP2A is highly expressed in hepatocellular carcinoma and predicts poor
      prognosis.
AB  - BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is highly
      expressed in hepatocellular carcinoma (HCC) and promotes cell proliferation, cell
      invasion, and aggressive tumor behavior. However, there have been few studies on
      the usefulness of CIP2A as an independent prognostic index of HCC. In the current
      study, the aim was to explore the association between CIP2A expression and
      prognosis in HCC. METHODS: The expression of CIP2A and c-MYC was examined by
      immunohistochemistry in 136 HCC specimens. CIP2A mRNA expression in 27 HCC
      tissues was also analyzed using quantitative reverse-transcription polymerase
      chain reaction. The prognostic significance was analyzed by the Kaplan-Meier
      survival method and log-rank test. Cox regression was adopted for univariate and
      multivariate analysis of prognostic factors. RESULTS: CIP2A protein was found to
      be highly expressed in human liver cancer samples (85/136, 62.5%) and correlated
      with poor survival (P<0.05). The liver cancer tissues examined exhibited much
      higher levels of CIP2A mRNA compared with their corresponding normal tissues
      (19/27, 70.3%). Furthermore, CIP2A mRNA levels were correlated with c-MYC mRNA
      levels. In addition, the highly expressed CIP2A was associated with recurrence
      (P=0.014) and invasion (P=0.017) of HCC. Patients with high CIP2A expression had
      both poorer overall survival (OS) and disease-free survival (DFS). On
      multivariate analysis, the CIP2A status was a significant prognostic factor for
      OS and DFS (P=0.017, P=0.026, respectively). CONCLUSIONS: CIP2A overexpression
      may be useful as an independent prognostic biomarker for OS and DFS of HCC.

PMID- 22847159
TI  - Detection of human papillomavirus in anal specimens using the hybrid capture 2
      assay.
AB  - The hc2 human papillomavirus DNA test (HC2) is effective when screening women for
      cervical dysplasia, and it might be effective in the screening for anal
      dysplasia. Differences between the anal and the cervical canals could affect the
      test performance. This prospective study (n=292) measured the HC2 signal and in
      agreement with a histologic endpoint of high-grade dysplasia for anal specimens
      collected in various ways. Sensitivities were 91%, 85%, and 62% for specimens
      collected in a sample transport medium and a liquid-based cytology medium
      processed by Gyn or Non-Gyn protocol, respectively. HC2 sensitivity and
      specificity to predict high-grade anal dysplasia were similar for brush or swab
      specimen collections, but HC2 signal was 6 times higher with the brush.
      Specificity and sensitivity were similar whether the sample was collected first
      or after a cytology sample for brush or swab, but swab specimens at the second
      collection had an HC2 signal (mean) 48% lower than that of the first collection,
      and the swab cellularity was lower. The presence of maximum stool decreased the
      HC2 signal in anal swab specimens. Consensus polymerase chain reaction (PCR)
      confirmed that the 13 human papillomavirus probe types in HC2 were optimal for
      performance. HC2 could potentially be further investigated for use in screening
      anal dysplasia. A larger prospective study is indicated.

PMID- 22847160
TI  - Impact of thawing on reference gene expression stability in renal cell carcinoma
      samples.
AB  - More and more samples are obtained from biobanks for biomedical research;
      however, some of these samples may undergo thawing before processing. We aim to
      evaluate the reference gene expression stability in thawed renal cell carcinoma
      samples. Sixteen matched malignant and nonmalignant renal tissue samples were
      obtained and each sample was divided into 4 aliquots before being snap frozen and
      stored at -80 degrees C. By quantitative real-time polymerase chain reaction, a
      time-course study was conducted on the thawed tissue to evaluate the expression
      stability of a panel of the 10 most frequently used reference genes in renal cell
      carcinom samples: ACTB, ALAS1, B2M, GAPDH, HMBS, HPRT, PPIA, RPLP0,TBP, and TUBB.
      As shown by geNorm M values, PPIA was the most stable gene at the 0-, 15-, and 30
      minute time points (M=0.82, 0.85, and 0.76, respectively), whereas GAPDH was
      ranked last at the 5-, 15-, and 30-minute time points (M=1.38, 1.44, and 1.39,
      respectively). A positive correlation was found by linear regression between the
      thawing time and 2 to the power of crossing point values of all candidate
      reference genes (P<0.05). The mean coefficient of variance of all reference genes
      increased significantly at time points 5, 15, and 30 minutes compared with 0
      minutes (P<0.01). In conclusion, using the geNorm algorithm, PPIA was identified
      as the most stably expressed gene between malignant and nonmalignant renal tissue
      samples that were thawed for similar time periods. All the reference genes showed
      high variations along with the thawing time; it should be recommended to use a
      combination of several candidate reference genes when comparing samples thawed
      for different time periods.

PMID- 22847161
TI  - Potential association between ANXA4 polymorphisms and aspirin-exacerbated
      respiratory disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome
      characterized by bronchoconstriction after ingestion of nonsteroidal anti
      inflammatory drugs including aspirin. The Ca concentration in bronchial
      epithelial cells is an important factor for bronchoconstriction. Human annexin A4
      (ANXA4) is predominantly expressed in the secretory epithelia in the lung,
      stomach, intestine, and kidney. Furthermore, translocation and induction of ANXA4
      have been observed in human Ca-depleted neutrophils. To investigate the
      association between annexin A4 polymorphisms and the risk of AERD, we have
      genotyped 21 variants from 102 AERD subjects and 429 aspirin-tolerant asthma
      (ATA) controls. Logistic analyses controlling for sex, smoking status, and atopy
      as covariates were performed to estimate the association between the annexin A4
      polymorphisms and AERD. Among these variants, 8 polymorphisms (rs2168116,
      rs4853017, rs6546547, rs13428251, rs7577864, rs7559354, rs7588022, and rs3816491)
      and 2 haplotypes (ANXA4-ht3 and ANXA4-ht5) were significantly associated with the
      risk of AERD. One common polymorphism in intron 11, rs3816491, showed the
      strongest association signal with susceptibility to aspirin-AERD even after
      multiple testing corrections (OR=0.57; 95% confidence interval 0.40-0.83;
      P=0.003; P=0.045 in the codominant model). Although further functional
      evaluations of replication studies in larger cohorts are required, our findings
      suggest that the annexin A4 could have susceptibility for AERD.

PMID- 22847162
TI  - Confirmation of the spinal motor neuron gene 2 (SMN2) copy numbers by real-time
      PCR.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by
      mutation or deletion of the survival motor neuron gene 1 (SMN1). SMN2, a copy
      gene, influences the severity of SMA and may be used in somatic gene therapy of
      patients with SMA in the future. The SMA carrier analysis developed at the
      Institute of Medical Genetics, Catholic University (Rome), on the Applied
      Biosystems real-time PCR instruments by Dr Danilo Tiziano and his group, provides
      a robust workflow to evaluate SMA carrier status. In this study, the SMN2 copy
      number was confirmed on 22 patients by developing our own assay on the basis of a
      relative real-time PCR system using the 7500 Fast Real-Time PCR System.

PMID- 22847163
TI  - Concomitant BCR-ABL1 translocation and JAK2(V617F) mutation in three patients
      with myeloproliferative neoplasms.
AB  - Chronic myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic
      stem cells, which fall into distinct categories based on a number of
      characteristics including the presence of the BCR-ABL1 gene fusion (chronic
      myelogenous leukemia) or the JAK2(V617F) mutation (polycythemia vera, primary
      myelofibrosis, and essential thrombocythemia). One of the criteria in the 2008
      World Health Organization Classification divides MPN into different categories
      based on the presence of an underlying genetic abnormality, however the WHO does
      not currently address the classification of myeloproliferative neoplasms that
      have more than one genetic abnormality. The coexistence of a JAK2(V617F) mutation
      and BCR-ABL1 is rare, and to our knowledge, less than 25 cases have been reported
      in the literature. Our case series examines the clinical, histopathologic, and
      genetic features of 3 patients with myeloproliferative neoplasms characterized by
      concomitant BCR-ABL1 and JAK2(V617F). The implications for diagnosis and
      treatment of patients with concomitant BCR-ABL1 and JAK2(V617F) are discussed as
      well as how the BCR-ABL1 and JAK2(V617F)-positive clones may be related to one
      another.

PMID- 22847164
TI  - Molecular diagnosis for a fatal case of very long-chain acyl-CoA dehydrogenase
      deficiency in Hong Kong Chinese with a novel mutation: a preventable death by
      newborn screening.
AB  - Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the most
      common fatty acid oxidation defects that cause sudden unexpected deaths in
      infants. The death attributed to VLCAD deficiency can be prevented by early
      diagnosis with expanded newborn screening using tandem mass spectrometry. A
      favorable outcome can be achieved with early diagnosis and prompt treatment.
      However, such newborn screening has not yet been available in Hong Kong. We
      report a 2-month-old boy who succumbed 5 hours after admission with the diagnosis
      of VLCAD deficiency confirmed by genetic analysis performed after death. The
      patient was compound heterozygous for a novel splicing mutation ACADVL
      NM_000018.2:c.277+2T>G; NC_000017.10:g.7123997T>G and a known disease-causing
      mutation ACADVL NM_000018.2:c.388_390del; NP_000009.1: p.Glu130del. Family
      screening was performed for at-risk siblings. The rapid downhill course of the
      patient clearly illustrates the need of newborn screening for early diagnosis.
      Our patient was asymptomatic before metabolic decompensation. However, once
      metabolic decompensation occurred, rapid deterioration and death followed, which
      obviated the opportunity to diagnose and treat. The only way to save these
      patients' lives and improve their outcome is early diagnosis and appropriate
      treatment. Therefore, we strongly urge the implementation of newborn screening
      using tandem mass spectrometry for VLCAD deficiency and other highly treatable
      inborn errors of metabolism in Hong Kong.

PMID- 22847165
TI  - Prevention: Polypills reduce CVD risk factors.

PMID- 22847167
TI  - Diabetes: Does aspirin increase the risk of major bleeds?

PMID- 22847168
TI  - Surgery: No benefit of acadesine in CABG.

PMID- 22847169
TI  - Do miRNAs have a deep evolutionary history?
AB  - The recent discovery of microRNAs (miRNAs) in unicellular eukaryotes, including
      miRNAs known previously only from animals or plants, implies that miRNAs have a
      deep evolutionary history among eukaryotes. This contrasts with the prevailing
      view that miRNAs evolved convergently in animals and plants. We re-evaluate the
      evidence and find that none of the 73 plant and animal miRNAs described from
      protists meet the required criteria for miRNA annotation and, by implication,
      animals and plants did not acquire any of their respective miRNA genes from the
      crown ancestor of eukaryotes. Furthermore, of the 159 novel miRNAs previously
      identified among the seven species of unicellular protists examined, only 28 from
      the algae Ectocarpus and Chlamydomonas, meet the criteria for miRNA annotation.
      Therefore, at present only five groups of eukaryotes are known to possess miRNAs,
      indicating that miRNAs have evolved independently within eukaryotes through
      exaptation of their shared inherited RNAi machinery.

PMID- 22847170
TI  - Clinical recognition of mid-aortic syndrome in children.
AB  - Mid-aortic syndrome is characterized by narrowing of the abdominal aorta, usually
      with the involvement of renal arteries and other visceral branches. The
      combination of the presence of an abdominal bruit, diminished or absent
      pulsations of the lower extremities, and a blood pressure discrepancy between
      upper and lower extremities is the classic triad associated with mid-aortic
      syndrome. However, it has a wide variety of clinical symptoms, and awareness of
      the variable presentation can lead to early diagnosis of the vascular anomaly. We
      report three cases presenting at three different stages of this disease, such as
      hydrops fetalis, refractory hypertension, and intracerebral bleeding. In
      conclusion, these cases highlight the importance of blood pressure measurements
      in all patients and accurate physical examination for early recognition of a mid
      aortic syndrome.

PMID- 22847171
TI  - Sketched x-rays: Calcinosis universalis.
AB  - Calcinosis universalis (CU) is a known complication of dermatomyositis
      manifesting as calcified nodules and plaques localized in subcutaneous tissue,
      fascial planes, tendons, or intramuscular regions. We report a case and image of
      CU in a 9-year-old boy diagnosed with juvenile dermatomyositis (JDM).

PMID- 22847166
TI  - Diagnosis and management of Chagas disease and cardiomyopathy.
AB  - Chagas cardiomyopathy is the most severe and life-threatening manifestation of
      human Chagas disease--a 'neglected' tropical disease caused by the protozoan
      parasite Trypanosoma cruzi. The disease is endemic in all continental Latin
      American countries, but has become a worldwide problem because of migration of
      infected individuals to developed countries, mainly in Europe and North America.
      Chagas cardiomyopathy results from the combined effects of persistent parasitism,
      parasite-driven tissue inflammation, microvascular and neurogenic dysfunction,
      and autoimmune responses triggered by the infection. Clinical presentation varies
      widely according to the extent of myocardial damage, and manifests mainly as
      three basic syndromes that can coexist in an individual patient: heart failure,
      cardiac arrhythmia, and thromboembolism. NYHA functional class, left ventricular
      systolic function, and nonsustained ventricular tachycardia are important
      prognostic markers of the risk of death. Management of Chagas cardiomyopathy
      focuses on the treatment of the three main syndromes. The use of beta-blockers in
      patients with Chagas disease and heart failure is safe, well tolerated, and
      should be encouraged. Most specialists and international institutions now
      recommend specific antitrypanosomal treatment of patients with chronic Chagas
      disease, even in the absence of evidence obtained from randomized clinical
      trials. Further research on the management of patients with Chagas cardiomyopathy
      is necessary.

PMID- 22847172
TI  - "Surface map" of the appendix: a novel tool for the preoperative demonstration of
      appendicular location with reference to McBurney?s point using a multidetector
      CT.
AB  - PURPOSE: In this study, we evaluated the role and relevance of multidetector
      computed tomography (MDCT) "surface map" of the appendix in demonstrating the
      variations in the location of the appendicular base with reference to McBurney's
      point and its likely clinical implications during an open appendicectomy.
      MATERIALS AND METHODS: This prospective study included a total of 74 patients who
      underwent an MDCT study of the abdomen for various clinical indications. Post
      processing of the data was performed and a "surface map" of the appendicular base
      was reconstructed with a superimposed measurement grid. The variation in the
      appendicular base location with reference to McBurney's point was analyzed along
      the cranio-caudal and medio-lateral axes. RESULTS: The maximum deviation in the
      location of the appendicular base was +10.0 cm along the cranio-caudal axis and 
      4.2 cm along the medio-lateral axis. The average cranio-caudal deviation was
      +2.79 cm, while the average medio-lateral deviation was +0.146 cm. In the
      subgroup of 16 patients who had appendicular inflammation, the maximum deviation
      was +8.8 cm along the cranio-caudal axis and +3.0 cm along the medio-lateral
      axis. The average cranio-caudal deviation in this subgroup of patients was +2.77
      cm; the average medio-lateral deviation was +0.77 cm. CONCLUSION: The MDCT
      "surface map" of the appendix is an effective tool that can convey precise
      information regarding appendix location to the operating surgeon. There are
      significant variations in the location of the appendicular base with reference to
      McBurney's point. These variations are more pronounced along the cranio-caudal
      axis than the medio-lateral axis. Accurate preoperative localization of the
      appendicular base with MDCT will help surgeons optimize the initial incision for
      an open appendicectomy, thus, minimize extension-related incision risks.

PMID- 22847173
TI  - Expertise in performance assessment: assessors' perspectives.
AB  - The recent rise of interest among the medical education community in individual
      faculty making subjective judgments about medical trainee performance appears to
      be directly related to the introduction of notions of integrated competency-based
      education and assessment for learning. Although it is known that assessor
      expertise plays an important role in performance assessment, the roles played by
      different factors remain to be unraveled. We therefore conducted an exploratory
      study with the aim of building a preliminary model to gain a better understanding
      of assessor expertise. Using a grounded theory approach, we conducted seventeen
      semi-structured interviews with individual faculty members who differed in
      professional background and assessment experience. The interviews focused on
      participants' perceptions of how they arrived at judgments about student
      performance. The analysis resulted in three categories and three recurring themes
      within these categories: the categories assessor characteristics, assessors'
      perceptions of the assessment tasks, and the assessment context, and the themes
      perceived challenges, coping strategies, and personal development. Central to
      understanding the key processes in performance assessment appear to be the
      dynamic interrelatedness of the different factors and the developmental nature of
      the processes. The results are supported by literature from the field of
      expertise development and in line with findings from social cognition research.
      The conceptual framework has implications for faculty development and the design
      of programs of assessment. 

PMID- 22847174
TI  - Accumulation of autofluorescent storage material in brain is accelerated by
      ischemia in chloride channel 3 gene-deficient mice.
AB  - Autofluorescent storage material (ASM) is an aging pigment that accumulates
      during the normal course of senescence. Although the role of ASM has yet to be
      fully elucidated, ASM has been implicated in age-related neurodegeneration. In
      this study, we determined the level of ASM in chloride channel 3 (ClC-3) gene
      deficient (KO) mice both in response to aging and following mild global ischemia.
      To understand the mechanism of action of the ASM, mice subjected to ischemia were
      treated with the cyclooxygenase (COX) inhibitor indomethacin or with the
      noncompetitive glutamate receptor antagonist MK-801. ClC-3 KO mice displayed age
      related neurodegeneration of the neocortex as well as the hippocampus. The
      cortical layers in particular granular layers became thinner with aging. ASM
      accumulated in the brains of ClC-3 KO mice was increased seven- to 50-fold over
      that observed in the corresponding regions of their wild-type littermates. Young
      wild-type mice survived longer than age-matched ClC-3 KO mice after permanent
      global ischemia. However, in the case of older animals, the survival curves were
      similar. The ASM also increased four- to fivefold 10 days after mild global
      ischemia, an effect that was suppressed by treatment with indomethacin and MK
      801. These results suggest that temporary ischemia might trigger a process
      similar to aging in the brain, mimicking the effect of age-related
      neurodegenerative diseases.

PMID- 22847175
TI  - Influence of fungicidal activity against Candida tropicalis on the efficacy of
      micafungin and liposomal amphotericin B in a neutropenic murine lethal infection
      model.
AB  - OBJECTIVES: To investigate the correlation between in vitro killing activity and
      in vivo efficacy of micafungin (MCFG) and liposomal amphotericin B (L-AMB)
      against Candida tropicalis in a neutropenic murine lethal infection model.
      METHODS: Candida albicans (one strain) and C. tropicalis (three strains) were
      tested in time-kill studies. Cyclophosphamide-treated mice were inoculated
      intravenously with each strain. One day after inoculation, antifungals were
      administered intravenously once daily for 1 or 3 days. RESULTS: MCFG exhibited
      fungicidal activity against C. albicans ATCC 90029 and C. tropicalis SP-20142,
      and fungistatic activity against C. tropicalis ATCC 42678 and SP-20047. The
      ED(50)s (dosage that results in 50% survival) of MCFG for C. tropicalis ATCC
      42678 and SP-20047 (4.1-50 mg/kg) were higher than those for other strains (1.6
      12 mg/kg). A 1-day course of MCFG was not effective against C. tropicalis ATCC
      42678 and SP-20047 at the clinical dose (5 mg/kg), which achieved an AUC level
      almost equal to that of 100 mg in humans, whereas a 3-day course of 5 mg/kg MCFG
      was efficacious against all strains. In contrast, L-AMB showed fungicidal
      activity against all strains tested and the ED(50)s of L-AMB were 0.08-0.65
      mg/kg. In both treatment regimens, the minimum effective doses of L-AMB (<=0.5
      mg/kg) were less than the clinical dosage (<=5 mg/kg). CONCLUSIONS: The in vivo
      efficacy of MCFG and L-AMB showed a correlation with the in vitro killing
      activity. At the clinical dose, L-AMB exerted anti-C. tropicalis activity within
      a shorter treatment period than MCFG.

PMID- 22847176
TI  - Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic
      steatosis in LDLR(-/-) mice.
AB  - Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because
      inflammation can modulate lipid metabolism and vice versa, we hypothesized that
      combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti
      inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect
      of FO. LDLR(-/-) mice were fed a high-fat diet supplemented with 6% olive oil or
      FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking
      water). FO reduced plasma total cholesterol by 30% but, in combination with Indo,
      exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE)
      and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo
      (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes
      modulating lipid metabolism and reduced the expression of inflammatory genes
      compared with control. The mRNA and/or protein expression of pregnane X receptor
      (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid
      metabolism are increased to a greater extent in mice that received FO + Indo.
      Moroever, the nuclear level of PXR is significantly increased in FO + Indo group.
      Combining FO with COXIBs may exert their beneficial effects on inflammation and
      lipid metabolism via PXR and cytochrome P450.

PMID- 22847177
TI  - Characterization of a novel HMG-CoA lyase enzyme with a dual location in
      endoplasmic reticulum and cytosol.
AB  - A novel lyase activity enzyme is characterized for the first time: HMG-CoA lyase
      like1 (er-cHL), which is a close homolog of mitochondrial HMG-CoA lyase (mHL).
      Initial data show that there are nine mature transcripts for the novel gene
      HMGCLL1, although none of them has all its exons. The most abundant transcript is
      called "variant b," and it lacks exons 2 and 3. Moreover, a three-dimensional
      model of the novel enzyme is proposed. Colocalization studies show a dual
      location of the er-cHL in the endoplasmic reticulum (ER) and cytosol, but not in
      mitochondria or peroxisomes. Furthermore, the dissociation experiment suggests
      that it is a nonendoplasmic reticulum integral membrane protein. The kinetic
      parameters of er-cHL indicate that it has a lower V(max) and a higher substrate
      affinity than mHL. Protein expression and lyase activity were found in several
      tissues, and were particularly strong in lung and kidney. The occurrence of er
      cHL in brain is surprising, as mHL has not been found there. Although mHL
      activity is clearly associated with energy metabolism, the results suggest that
      er-cHL is more closely related to another metabolic function, mostly at the
      pulmonary and brain level.

PMID- 22847179
TI  - Effect of multi-walled carbon nanotubes incorporation into benzyl methacrylate
      monolithic columns in capillary liquid chromatography.
AB  - This work describes the preparation of polymer based monolithic materials and
      their use as stationary phases in capillary liquid chromatography. Multi-walled
      carbon nanotubes (MWCNT) were incorporated into a mixture containing benzyl
      methacrylate (BMA) and ethylene dimethacrylate (EDMA) as co-monomers. The
      optimized porogenic mixture was a ternary solution composed of cyclohexanol, 1,4
      butandiol and butanol which resulted in a stable and homogeneous suspension. Six
      capillary columns with increasing amounts of MWCNT, from 0 to 0.4 mg mL(-1), were
      prepared by thermal polymerization in 0.32 mm (i.d.) and 150 mm length fused
      silica tubing. The chromatographic evaluation showed that the synthesized
      monolithic beds were mechanically stable while their porosity and permeability
      increased with the MWCNT content. The prepared capillary columns were tested for
      the separation of mixtures of ketones and phenols at an optimum flow rate of 2
      MUL min(-1). The results showed that incorporation of MWCNT slightly affected the
      retention while it enhanced the column efficiency by increasing the column
      efficiency by a factor of up to 9. This effect corresponded also to an improved
      resolution and full separation of the solutes.

PMID- 22847178
TI  - Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids
      on postprandial vascular function.
AB  - Our objective was to determine whether the endothelial nitric oxide synthase
      (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA
      enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated
      fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n
      = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two
      occasions, with and without the substitution of 0.07 g fat/kg body weight with LC
      n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was
      measured before and after NEFA elevation (240 min), with blood samples taken
      every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and
      increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change
      in FMD response to the different fat loads between the Asp298 and Glu298
      genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside
      induced reactivity, measured by laser Doppler imaging with iontophoresis, was
      significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but
      not in males. Elevated NEFA influences both endothelial-dependent and endothelial
      independent vasodilation during the postprandial phase. Effects of fat
      composition appear to be genotype and gender dependent, with the greatest
      difference in vasodilatory response to the two fat loads seen in the Asp298
      females.

PMID- 22847180
TI  - The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor
      malignancy and drug resistance.
AB  - Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The
      non-malignant form of the disease is termed chondroma. Correctly distinguishing
      between the two forms is essential for making therapeutic decisions. However, due
      to their similar histological appearances and the lack of a reliable diagnostic
      marker, it is often difficult to distinguish benign tumors from low-grade
      chondrosarcoma. Therefore, it is necessary to search for a potential marker that
      has diagnostic and prognostic values in chondrosarcoma. In this study, we
      demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related
      factor (LRF) expression was associated with increased malignancy in human
      chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically
      reduced proliferation of chondrosarcoma cell lines and effectively induced
      senescence in these cells. This could be attributed to the observation that LRF
      depleted cells were arrested at the G(1) phase, and had increased p53 and p21
      expression. Moreover, LRF depletion not only drastically reduces the cellular
      migration and invasion potentials of chondrosarcoma cells but also sensitized
      these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We
      conclude that LRF is a survival factor in chondrosarcomas and its expression
      correlates with tumor malignancy and chemoresistance. Our data implicate the
      potential role of LRF as both a diagnostic marker and therapeutic target for
      chondrosarcomas.

PMID- 22847181
TI  - Mitochondrial uncoupling protein 2 regulates the effects of paclitaxel on Stat3
      activation and cellular survival in lung cancer cells.
AB  - Growing evidence suggests that Stat3 contributes to chemoresistance. However, the
      impact of chemotherapy on Stat3 activity is unclear. We found that paclitaxel
      activated Stat3 in the human lung cancer cell lines PC14PE6AS2 (AS2) and H157,
      whereas it reduced Stat3 activation in A549 and H460 cells. Pretreatment of AS2
      and H157 cells with rotenone, an inhibitor of mitochondrially produced reactive
      oxygen species (ROS), or carbonyl cyanide p-(trifluoromethoxy)-phenylhydrazone
      (FCCP), a mitochondrial uncoupler, suppressed the paclitaxel-induced activation
      of Stat3. Uncoupling protein 2 (UCP-2), located in the inner membrane of the
      mitochondria, can reduce ROS production in conditions of oxidative stress. UCP-2
      protein expression in the four cancer cell lines was higher than that in normal
      lung epithelial cells (NL-20), but its expression was lower in AS2 and H157 cells
      relative to A549 and H460 cells. Silencing high UCP-2 expression with small
      interfering RNA (siRNA) in A549 and H460 cells restored paclitaxel-induced Stat3
      activation. In addition, paclitaxel-induced Stat3 activation led to the
      upregulation of survivin and Mcl-1, which in turn facilitated cell survival.
      Moreover, the CL1-5 subline had lower UCP-2 expression relative to the parental
      CL1-0 cells. Treatment with paclitaxel activated Stat3 in CL1-5 but not in CL1-0
      cells, whereas in CL1-5 cells, the overexpression of UCP-2 with complementary DNA
      (cDNA) blocked Stat3 activation. In lung cancer patients, low UCP-2 expression in
      cancer cells was a predictor of a poor response to chemotherapy. Therefore, UCP-2
      modulates the ROS/Stat3 signaling pathway and response to chemotherapy treatment
      in lung cancer cells. Targeting UCP-2, ROS and Stat3 pathways may improve
      anticancer therapies.

PMID- 22847182
TI  - Assessment of the levels of polybrominated diphenyl ethers in blood samples from
      Guadalajara, Jalisco, Mexico.
AB  - The purpose of this study was to measure levels of polybrominated diphenyl ethers
      (PBDEs) in the blood of children (50 individuals) living in Guadalajara, Jalisco,
      Mexico. We analyzed six PBDE congeners by gas chromatography-mass spectrometry.
      Total PBDE levels ranged from not detectable (nd) to 15.2 MUg/L on a whole-weight
      basis and from nd to 6,435 ng/g lipid on a lipid-weight basis. The dominant
      congener in our study was BDE-153, followed by BDE-154, BDE-99, BDE-100, and BDE
      47. Levels of BDE-209 were below the detection limit. Our data indicate that
      children living in the areas studied in this work are exposed to high levels of
      PBDEs.

PMID- 22847183
TI  - Lead bone toxicity in growing rats exposed to chronic intermittent hypoxia.
AB  - Lead chronic intoxication under hypoxic conditions revealed growth retardation in
      growing rats and damages on femoral and mandibular bones that predispose to
      fractures. These findings aimed us to investigate if bone material and geometric
      properties, bone mass in terms of histomorphometry or antioxidant capacity are
      also impaired in such experimental model. Combined treatments significantly
      reduced hemimandible cross sectional geometry and intrinsic stiffness (-16% and 
      34%); tibia and hemimandible bone volume (-45% and -40%) and growth plate
      cartilage thickness (-19%). These results show a previously unreported toxic
      effect of lead on mandible however, longer studies should be necessary to
      evaluate if an adaptation of bone architecture to maintain structural properties
      may occur and if the oxidative stress can be identified as the primary
      contributory agent in the pathogenesis of lead poisoning.

PMID- 22847185
TI  - DNA methylation based biomarkers: practical considerations and applications.
AB  - A biomarker is a molecular target analyzed in a qualitative or quantitative
      manner to detect and diagnose the presence of a disease, to predict the outcome
      and the response to a specific treatment allowing personalized tailoring of
      patient management. Biomarkers can belong to different types of biochemical
      molecules such as proteins, DNA, RNA or lipids, whereby protein biomarkers have
      been the most extensively studied and used, notably in blood-based protein
      quantification tests or immunohistochemistry. The rise of interest in epigenetic
      mechanisms has allowed the identification of a new type of biomarker, DNA
      methylation, which is of great potential for many applications. This stable and
      heritable covalent modification mostly affects cytosines in the context of a CpG
      dinucleotide in humans. It can be detected and quantified by a number of
      technologies including genome-wide screening methods as well as locus- or gene
      specific high-resolution analysis in different types of samples such as frozen
      tissues and FFPE samples, but also in body fluids such as urine, plasma, and
      serum obtained through non-invasive procedures. In some cases, DNA methylation
      based biomarkers have proven to be more specific and sensitive than commonly used
      protein biomarkers, which could clearly justify their use in clinics. However,
      very few of them are at the moment used in clinics and even less commercial tests
      are currently available. The objective of this review is to discuss the
      advantages of DNA methylation as a biomarker, the practical considerations for
      their development, and their use in disease detection, prediction of outcome or
      treatment response, through multiple examples mainly focusing on cancer, but also
      to evoke their potential for complex diseases and prenatal diagnostics.

PMID- 22847184
TI  - Effect of L-tyrosine in vitro and in vivo on energy metabolism parameters in
      brain and liver of young rats.
AB  - Tyrosinemia is a rare disease caused by a single mutation to the gene that code
      for the enzyme responsible for tyrosine catabolism. Because the mechanisms
      underlying the neurological dysfunction in hypertyrosinemic patients are poorly
      understood, we evaluated the in vitro and in vivo effect of L-tyrosine on the
      activities of the enzymes citrate synthase, malate dehydrogenase, succinate
      dehydrogenase and complexes of the mitochondrial respiratory chain in the brains
      and livers of young rats. Thirty-day-old Wistar rats were killed by decapitation,
      and the brains and livers were harvested. L-Tyrosine (0.1, 1.0, 2.0 or 4.0 mM)
      was added to the reaction medium. For in vivo studies, Wistar rats were killed 1
      h after a single intraperitoneal injection of either tyrosine (500 mg/kg) or
      saline. The activities of energy metabolism enzymes were evaluated. In this
      research, we demonstrated in vitro that L-tyrosine inhibited citrate synthase
      activity in the posterior cortex and that succinate dehydrogenase was increased
      in the posterior cortex, hippocampus, striatum and liver. The complex I activity
      was only inhibited in the hippocampus, whereas complex II activity was inhibited
      in the hippocampus, cortex and liver. Complex IV activity decreased in the
      posterior cortex. The acute administration of L-tyrosine inhibited enzyme malate
      dehydrogenase, citrate synthase and complexes II, II-III and IV in the posterior
      cortex and liver. The enzyme succinate dehydrogenase and complex I activity were
      inhibited in the posterior cortex and increased in the striatum. These results
      suggest impairment in energy metabolism that is likely mediated by oxidative
      stress.

PMID- 22847186
TI  - Enzymatic conversion of xylan residues from dilute acid-pretreated corn stover.
AB  - Enzymatic conversion of oligomeric xylose and insoluble xylan remaining after
      effective pretreatment offers significant potential to improve xylan-to-xylose
      yields while minimizing yields of degredation products and fermentation
      inhibitors. In this work, a commercial enzyme cocktail is demonstrated to convert
      up to 70 % of xylo-oligomers found in dilute acid-pretreated hydrolyzate liquor
      at varying levels of dilution when supplemented with accessory enzymes targeting
      common side chains. Commercial enzyme cocktails are also shown to convert roughly
      80 % of insoluble xylan remaining after effective high-solids, dilute acid
      pretreatment.

PMID- 22847187
TI  - Immobilization of Pseudomonas fluorescens lipase onto magnetic nanoparticles for
      resolution of 2-octanol.
AB  - The lipase from Pseudomonas fluorescens (Lipase AK, AKL) was immobilized onto the
      magnetic Fe(3)O(4) nanoparticles via hydrophobic interaction. Enzyme loading and
      immobilization yield were determined as 21.4+/-0.5 mg/g and 49.2+/-1.8 %,
      respectively. The immobilized AKL was successfully used for resolution of 2
      octanol with vinyl acetate used as acyl donor. Effects of organic solvent, water
      activity, substrate ratio, and temperature were investigated. Under the optimum
      conditions, the preferred isomer for AKL is the (R)-2-octanol and the highest
      enantioselectivity (E=71.5+/-2.2) was obtained with a higher enzyme activity
      (0.197+/-0.01 MUmol/mg/min). The results also showed that the immobilized lipase
      could be easily separated from reaction media by the magnetic steel and remained
      89 % of its initial activity as well as the nearly unchanged enantioselectivity
      after five consecutive cycles, indicating a high stability in practical
      operation.

PMID- 22847188
TI  - Do demographic and cultural differences exist in adulthood?

PMID- 22847189
TI  - Perceived health is partially associated with the symptomatological profile in
      patients with benign and severe conditions: the case of congenital heart disease.
AB  - PURPOSE: Individuals with serious medical conditions can perceive their health
      status as good. This might be explained by the symptomatology inherent to the
      condition. Research in this respect is scarce. Congenital heart disease (CHD) is
      a spectrum of mild, moderate, and complex heart defects, representing more benign
      and severe chronic conditions. We investigated (1) symptomatology (i.e., symptom
      frequency and symptom distress) of CHD patients; (2) the extent to which
      symptomatology was independently related to perceived health; and (3) the
      relative importance of individual symptoms for perceived health. METHODS: A
      secondary data analysis on two separate patient samples (629 Belgian and 1,109
      Dutch patients) was conducted. Patients' symptomatology was measured with the
      TAAQOL-CHD. Perceived health was measured by the EQ-5Dvas in Belgian patients,
      and by a single item (EVGFP rating) of the SF-36 in Dutch patients. Linear
      regression analyses were performed to investigate the relationship between
      symptoms and perceived health, while controlling for sex, age, disease
      complexity, and functional status. RESULTS: The most frequently occurring
      symptoms were dizziness, palpitations, and nycturia. Symptom distress was
      associated with perceived health, independent of confounders. Symptom distress
      with respect to shortness of breath while walking; palpitations; and dizziness
      were independently related to perceived health. CONCLUSIONS: Perceived health in
      CHD patients is partially associated with their symptomatology. This finding
      underscores the possibility that differences in perceived health across patient
      groups with more benign and severe conditions may be caused by the different
      impact conditions have--in terms of symptoms--on the day-to-day life.

PMID- 22847190
TI  - Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro.
AB  - BACKGROUND: Several HIV protease mutations, which are resistant to clinical HIV
      protease inhibitors (PIs), have been identified. There is a great need for second
      generation PIs with different chemical structures and/or with an alternative mode
      of inhibition. Ginkgolic acid is a natural herbal substance and a major component
      of the lipid fraction in the nutshells of the Ginkgo biloba tree. The objective
      of this study was to determine whether ginkgolic acid could inhibit HIV protease
      activity in a cell free system and HIV infection in human cells.
      MATERIAL/METHODS: Purified ginkgolic acid and recombinant HIV-1 HXB2 KIIA
      protease were used for the HIV protease activity assay. Human peripheral blood
      mononuclear cells (PBMCs) were used for HIV infection (HIV-1SF162 virus),
      determined by a p24gag ELISA. Cytotoxicity was also determined. RESULTS:
      Ginkgolic acid (31.2 ug/ml) inhibited HIV protease activity by 60%, compared with
      the negative control, and the effect was concentration-dependent. In addition,
      ginkgolic acid treatment (50 and 100 ug/ml) effectively inhibited the HIV
      infection at day 7 in a concentration-dependent manner. Ginkgolic acid at a
      concentration of up to 150 ug/ml demonstrated very limited cytotoxicity.
      CONCLUSIONS: Ginkgolic acid effectively inhibits HIV protease activity in a cell
      free system and HIV infection in PBMCs without significant cytotoxicity.
      Ginkgolic acid may inhibit HIV protease through different mechanisms than current
      FDA-approved HIV PI drugs. These properties of ginkgolic acid make it a promising
      therapy for HIV infection, especially as the clinical problem of viral resistance
      to HIV PIs continues to grow.

PMID- 22847191
TI  - MicroRNA-10b targets E-cadherin and modulates breast cancer metastasis.
AB  - BACKGROUND: Recent studies have suggested that microRNA-10b (miR-10b) acts as a
      promoter of metastasis in breast cancer, although the underlying mechanism
      remains largely unknown. In this study, we provide the first evidence that E
      cadherin (E-cad) is a potential target of miR-10b. MATERIAL/METHOD: By applying
      gain-of-function and loss-of-function approaches in the metastatic breast cancer
      cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to
      regulate the cellular expression of E-cad and in vitro tumor cell invasion.
      RESULTS: Comparative expression analysis of miR-10b in benign breast lesions
      (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23)
      revealed that miR-10b transcription was uniquely up-regulated in metastatic
      cancers. The expression level of miR-10b positively correlated with tumor size,
      pathological grading, clinical staging, lymph node metastasis, Her2-positivity
      and tumor proliferation, but was negatively associated with estrogen receptor
      positivity, progesterone receptor-positivity and E-cad mRNA and protein levels.
      CONCLUSIONS: These findings indicate the existence of a novel E-cadherin-related
      mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR
      10b may be a useful biomarker of advanced progression and metastasis of breast
      cancer.

PMID- 22847192
TI  - beta-adrenoceptor regulates miRNA expression in rat heart.
AB  - BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs of 18-25 nucleotides that post
      transcriptionally regulate gene expression and are involved in a wide range of
      physiological and pathological conditions. The beta-adrenergic signaling pathway
      plays a fundamental role in regulation of heart function. The present study was
      designed to investigate the expression profile of miRNAs and functional
      implications under conditions of beta-adrenoceptor activation or inhibition in
      rat heart. MATERIAL/METHODS: Hemodynamic parameters were measured to assess heart
      function in Wistar rats treated with isoproterenol (ISO) or propranolol (PRO).
      miRNA expression was analyzed by miRNA Microarray and confirmed by real-time
      quantitative reverse transcription PCR (real-time qRT-PCR). RESULTS:
      Isoproterenol (ISO, a beta-adrenoceptor activator) and propranolol (PRO, a beta
      adrenoceptor inhibitor) induced differential miRNA expression profiles. Out of
      349 miRNAs measured, 43 were upregulated and nine downregulated in the ISO group,
      while five miRNAs were upregulated and 28 downregulated in PRO group. Among these
      altered miRNAs in both PRO and ISO groups, 11 were cardiac abundant and 11 showed
      opposite profiles between the PRO and ISO groups. The recognized anti
      hypertrophic miRNAs miR-1, miR-21 and miR-27b, and the pro-hypertrophic miRNAs
      miR-22, miR-24, miR-199a, miR-212 and miR-214, were upregulated in the ISO group.
      In the PRO group, pro-hypertrophic miRNA miR-30c was upregulated, whereas miR-212
      was downregulated. CONCLUSIONS: beta-adrenoceptor intervention alters miRNA
      expression profile, and miRNAs may be involved in the beta-adrenoceptor signaling
      pathway. Cardiomyocyte hypertrophy is a balanced process between pro-hypertrophic
      and anti-hypertrophic regulation and involves, at the very least, miRNA
      participation.

PMID- 22847193
TI  - Morphological and enzymatic changes caused by a long-term treatment of female
      rats with a low dose of gonadoliberin agonist and antagonist.
AB  - BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the
      hypothalamic-pituitary-gonadal axis. The use of these agents is generally
      considered to be safe; however, some observations suggest the possibility of
      adverse effects. MATERIAL/METHODS: We investigated whether a 3-months
      administration of a low dose (6 ug/kg b.w.) of dalarelin - a new agonist, and
      cetrorelix - a known antagonist of GnRH to female rats causes morphological
      changes in pituitary gland, ovaries, uterus and liver (HE and VG staining);
      effects on pituitary, hepatic and blood enzyme activities (histochemical and
      kinetic methods, respectively), and on the blood lipid profile (colorimetric
      methods); and to what extent these changes are reversible. RESULTS: Applying
      analogs effectively inhibited ovulation, affected the uterine endometrium and
      changed histological appearance of the liver (e.g., steatosis). They altered
      activities of marker enzymes of cellular respiration, gluconeogenesis and
      intracellular digestion in the liver and, partially in the pituitary gland,
      caused undesirable changes in the activities of aspartate aminotransferase,
      alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a
      concentration of cholesterol HDL fraction and triglycerides in the blood. Both
      morphological and enzymatic effects were more evident after antagonist
      administration; changes in the blood lipid profile were more evident after
      agonist administration. In both analogs histological and enzymatic changes
      persisted a relatively long time after the discontinuation of the treatment.
      CONCLUSIONS: The low dose of dalarelin and cetrorelix is sufficient to cause
      limited damage of hepatic cells and may modify the function of pituitary,
      ovaries, uterus and liver as well as other organs, even after discontinuation of
      the treatment.

PMID- 22847194
TI  - Disorders of erythrocyte structure and function in hypertensive patients.
AB  - BACKGROUND: The prevalence of hypertension is growing at an alarming rate.
      Increasing attention is being focussed on the oxidative stress accompanying this
      disease. In this study we examined the impact of this disease on some parameters
      of erythrocytes and human blood plasma. MATERIAL/METHODS: We examined the impact
      of hypertension on some parameters of erythrocytes and human plasma. The study
      involved 13 patients with hypertension and 19 healthy subjects. We determined
      lipid peroxidation, SH groups concentration, antioxidants enzymes activity,
      ATPase activity, total antioxidant capacity, total cholesterol level and
      erythrocyte membrane fluidity. RESULTS: We found an increased level of lipid
      peroxidation and the concentration of SH groups in membrane proteins in patients
      with hypertension, and a decrease in the activity of catalase and superoxide
      dysmutase. No changes were observed in glutathione peroxidase and ATPase
      activity, level of total antioxidant capacity, total cholesterol level and
      fluidity of erythrocyte membranes. CONCLUSIONS: These results suggest the
      existence of an impaired oxidative balance in hypertensive human erythrocytes.

PMID- 22847195
TI  - Protective effect of anti-oxidants on endothelial function in young Korean-Asians
      compared to Caucasians.
AB  - BACKGROUND: Previous studies show that Asians have an impaired blood flow
      response (BFR) to occlusion after a single high fat (HF) meal. The mechanism is
      believed to be the presence and susceptibility to high free radicals in their
      blood. The free radical concentration after a HF meal has not been examined in
      Asians. Further the BFR to heat after a single HF meal in Koreans has not been
      measured. MATERIAL/METHODS: This study evaluated postprandial endothelial
      function by measuring the BFR to vascular occlusion and local heat before and
      after a HF meal and the interventional effects of anti-oxidant vitamins on
      improving endothelial function in young Korean-Asians (K) compared to Caucasians
      (C) with these assessments. Ten C and ten K participated in the study (mean age
      25.3+/-3.6 years old). BFR to vascular occlusion and local heat and oxidative
      stress were assessed after a single low fat (LF) and HF meal at 2 hours compared
      to baseline. After administration of vitamins (1000 mg of vitamin C, 800 IU of
      vitamin E, and 300 mg of Coenzyme Q-10) for 14 days, the same measurements were
      made. RESULTS: This study showed that the skin BFR to vascular occlusion and
      local heat following a HF meal significantly decreased and free radicals
      significantly increased at 2 hours compared to baseline in K (p<.001), but not in
      C. When vitamins were given, the BFR to vascular occlusion and local heat before
      and after HF meal were not significantly different in K and C. CONCLUSIONS: These
      findings suggest that even a single HF meal can reduce endothelial response to
      stress through an oxidative stress mechanism but can be blocked by antioxidants,
      probably through scavenging free radicals in K. Since endothelial function
      improved even before a HF meal in K, endothelial damage from an Americanized diet
      may be reduced in K by antioxidants.

PMID- 22847196
TI  - Serum C-reactive protein as a possible marker to predict delayed hemorrhage after
      colonoscopic polypectomy.
AB  - BACKGROUND: Post-polypectomy hemorrhage is one of the complications of
      colonscopic polypectomy. And there is no definitive and convenient laboratory
      test that could be used to predict risk of delayed post-polypectomy hemorrhage.
      This research aimed to study risk prediction of delayed post-polypectomy
      hemorrhage using serum C-reactive protein (CRP) level as a marker.
      MATERIAL/METHODS: In a retrospective, case-controlled study, 302 cases of post
      polypectomy patients were divided into hemorrhage group and non-hemorrhage group.
      The CRP levels 24-hours after colonscopic treatment were compared between the two
      groups to assess whether elevated serum CRP levels in addition to other risk
      factors such as age, gender, smoking, alcohol consumption, hypertension (AHT) and
      size of polyps may predict risk of delayed post-polypectomy hemorrhage. RESULTS:
      The hemorrhage group had significantly higher levels of serum CRP (32.50+/-17.34
      mg/L vs. 6. 32+/-6.02 mg/dL) and were also having a higher incidence of
      hypertension compared to the non- hemorrhage group (both P<0.05). Patients with
      elevated serum CRP levels (>=10 mg/L) after colonscopic treatment are at a higher
      risk of developing post-polypectomy hemorrhage (OR 1.329, 95%CI 1.125-1.571) as
      compared with patients whose CRP levels were not increased. CONCLUSIONS: A higher
      level of serum CRP may serve as an indicator of delayed post-polypectomy
      hemorrhage and there appears to be a direct relationship between the serum CRP
      levels and the risk of post-polypectomy hemorrhage: the higher CRP levels the
      higher the risk of post-polypectomy hemorrhage.

PMID- 22847197
TI  - Analysis of bacteria from intestinal tract of FAP patients for the presence of
      APC-like sequences.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary disease induced
      by germ-line mutations in the tumor suppressor APC gene. These initiate the early
      stages of the adenoma-carcinoma sequence in familial, but also in sporadic (in
      80% to 90%), colon tumorigenesis. We found the presence of APC-like sequences in
      bacteria of FAP patients. MATERIAL/METHODS: We analyzed bacteria isolated from
      FAP patients' rectal swabs. Total bacterial DNA was isolated and analyzed for
      detection of APC-like sequences using PCR. We also tested DNA homology rate and
      APC-like protein production. RESULTS: We collected blood samples and rectal swabs
      from patients with confirmed diagnosis of FAP. They were analyzed for presence of
      sections from exon 15 of the APC gene. Most positive results were found in
      sections located exactly in the area called the MCR (mutation cluster region),
      where the highest frequency of APC gene mutations were identified. By sequencing
      PCR products from bacteria in section F-G together with a patient's DNA sample
      and human APC gene, we found a more than 90% DNA homology rate. We also confirmed
      production of APC-like protein using Western blotting. CONCLUSIONS: Our results
      suggested two hypotheses. The APC-like protein might have same function as a
      truncated APC product, which is synthesized in most cases of mutations of APC
      gene in the MCR region in colorectal cancer cells. Alternatively, we can consider
      the possible existence of horizontal transfer of genetic information between
      eukaryotic and prokaryotic cells. Our study can be considered as a pilot project.
      For confirmation of our hypotheses, further research is needed.

PMID- 22847198
TI  - Autonomic nervous system activity in constipation-predominant irritable bowel
      syndrome patients.
AB  - BACKGROUND: The main mechanism underlying irritable bowel syndrome is currently
      believed to be a dysfunction of the brain-gut axis. Autonomic nervous system
      dysfunction can contribute to development of irritable bowel syndrome symptoms by
      disturbing visceral sensations. MATERIAL/METHODS: Thirty patients with a
      diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy
      volunteers were included in the study. Resting and functional autonomic nervous
      system tests and percutaneous electrogastrography were performed. Plasma
      adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was
      analyzed. RESULTS: Increased sympathetic activation with disturbed
      parasympathetic function was demonstrated. Patients had substantially higher
      plasma catecholamine concentration, which confirms sympathetic overbalance.
      Hyperinsulinemia may explain sympathetic predominance followed by gastric and
      intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin
      titre may disturb brain-gut axis functioning and may be responsible for gastric
      motility deceleration. In electrogastrography, distinctly lower values of fasting
      normogastria percentage and dominant power were observed. Patients had
      substantially lower slow wave coupling percentage both in fasting and
      postprandial periods, which negatively correlated with plasma catecholamines
      level. Gastric myoelectrical activity disturbances may result from lack of
      sympatho-parasympathetic equilibrium. CONCLUSIONS: Central sympathetic influence
      within the brain-gut axis is most probably responsible for myoelectrical activity
      disturbances in irritable bowel syndrome patients.

PMID- 22847199
TI  - Mycoplasma pneumoniae in adult community-acquired pneumonia increases matrix
      metalloproteinase-9 serum level and induces its gene expression in peripheral
      blood mononuclear cells.
AB  - BACKGROUND: The objective of this study was to assess the concentration of
      metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) in peripheral
      circulation and their mRNA expression in peripheral blood mononuclear cells
      (PBMCs) in patients with CAP caused by M. pneumoniae. MATERIAL/METHODS: We
      prospectively analyzed MMPs in 40 hospitalized patients with M. pneumoniae CAP on
      admission, and in the convalescent phase. Twenty healthy men were used as
      controls. Quantitative real-time PCR and ELISA tests were used. RESULTS: MMP-9
      mRNA expression in PBMCs was increased in the acute phase of illness compared to
      the control group as well as in convalescent phase in which case it was
      statistically significant (Mann-Whitney; p=0.028). The same was found for MMP-9
      plasma levels (Mann-Whitney test; p<0.001; p=0.001). Circulating MMP-2
      concentration in acute patients was significantly lower than in the control group
      and convalescent phase (Mann-Whitney test; p=0.012; p=0.001), while no MMP-2 mRNA
      expression was found in PBMCs. The plasma level of MMP-9 correlated with
      leukocyte count in peripheral circulation (r=0.67, p<0.001). CONCLUSIONS: We
      conclude that M. pneumoniae in adult CAP induces activity of MMP-9 in peripheral
      blood circulation.

PMID- 22847200
TI  - Leptin and interferon-gamma as possible predictors of cesarean section among
      women with hypertensive disorders of pregnancy.
AB  - BACKGROUND: This study was designed to evaluate maternal levels of leptin and
      interferon-gamma (IFN-gamma) in pregnancy complicated with hypertension and to
      assess the role of cytokines in predicting the risk of cesarean section.
      MATERIAL/METHODS: This was a cohort study with a prospective follow-up. After
      proportional sampling procedure, the study included the follow-up of 40 women
      with hypertensive disorders of pregnancy (pregnancy-induced hypertension [PIH] or
      preeclampsia [PE]) and 40 uncomplicated pregnancies. Women were followed from the
      time of admission to the delivery. Levels of leptin and interferon-gamma were
      measured in serum samples from all women. A p-value <0.05 was considered as
      significant. RESULTS: Significant increase in IFN-gamma and leptin concentration
      in women with pre-eclampsia was observed. We found a significant 1.4-fold
      increase in the risk of birth by cesarean section associated with the increase of
      the IFN-gamma concentration by 0.1 pg/ml and almost 3-fold increase in the risk
      associated with the increase of the leptin concentration. CONCLUSIONS: IFN-gamma
      and leptin might be risk markers of cesarean section in hypertension disorders of
      pregnancy, but further studies supporting this evidence are needed.

PMID- 22847201
TI  - Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant
      alleles frequently distributed in the Czech population.
AB  - BACKGROUND: CYP2C9*3 allele has been reported to correlate with increased plasma
      concentration of fluvastatin active form in healthy volunteers. We analyzed the
      correlation between the CYP2C9 genotype and cholesterol-lowering effect of
      fluvastatin in human hypercholesterolemic patients. MATERIAL/METHODS: The study
      was prospective, without any interventions to standard procedures of
      hypolipidemic treatment. CYP2C9 genotype was determined by PCR-RFLP assay in 87
      patients on concomitant fluvastatin therapy, in 48 patients on monotherapy, and
      in a control group of 254 healthy volunteers of Czech nationality. Biochemical
      and clinical data were collected before the initiation of fluvastatin treatment
      and 12 weeks later. RESULTS: The frequency of CYP2C9 alleles did not differ
      significantly among groups of patients and volunteers. The most frequently
      observed allele was CYP2C9*2. Treatment with 80 mg of fluvastatin daily of 48
      patients on monotherapy for 12 weeks resulted in mean low-density lipoprotein
      cholesterol (LDL-C) reduction by 25%, mean serum total cholesterol (TC) reduction
      by 21%, and mean triglyceride (TG) reduction by 28%. The CYP2C9*1/*3 genotype was
      associated with a decrease in LDL-C levels (by 40.0% for CYP2C9*1/*3, but only by
      22.4% for CYP2C9*1/*1), and with the reduction of TC (by 28.6% in CYP2C9*1/*3
      versus 20.2% in CYP2C9*1/*1). CONCLUSIONS: In hypercholesterolemic patients, LDL
      C serum concentration was decreased more significantly in fluvastatin-treated
      subjects bearing the CYP2C9*1/*3 genotype compared to CYP2C9*1/*1 genotype.
      However, due to rare occurrence of some CYP genotypes, it was impossible to
      report a definitive positive genotype-fluvastatin effect association.

PMID- 22847202
TI  - Clinical parameters for prediction of successful labor induction after
      application of intravaginal dinoprostone in nulliparous Chinese women.
AB  - BACKGROUND: The aim of this study was to compare the possible clinical parameters
      for prediction of successful labor induction in Chinese nulliparous women.
      MATERIAL/METHODS: A retrospective, observational trial of labor induction was
      performed, using a single dose of 10 mg controlled-release dinoprostone for
      preinduction cervical ripening in 127 nulliparous women (gestational age 38-42
      weeks, singleton cephalic presentation). The characteristics of the women with
      successful labor induction (defined as vaginal delivery achieved on the day of
      admission; n=80) and failed labor induction (n=47) were compared. RESULTS: The
      main differences observed between the groups were gravidity (P<0.05), induction
      active labor interval (5.16+/-2.98 vs. 8.40+/-3.41; P<0.05) and birth weight
      (3421.11+/-368.14 vs. 3566.36+/-345.16; P<0.05). Logistic regression demonstrated
      that gravidity (P<0.05) and induction-active labor interval (P<0.05), but not
      Bishop score, were significant and independent contributing factors for
      successful labor induction. In the receiver operating characteristic curves for
      the prediction of successful labor induction, the best cut-off value for
      gravidity was 3 (95% confidence interval [CI] 0.64-0.83, P=0.000), and the best
      cut-off value for the induction-active labor interval was 7.96 (95%CI 0.66-0.85,
      P=0.000). CONCLUSIONS: Less gravidity and shorter induction-active labor interval
      predict successful labor induction with reasonable accuracy.

PMID- 22847203
TI  - Effects of living environment on the postoperative Scoliosis Research Society-24
      results in females with adolescent idiopathic scoliosis.
AB  - BACKGROUND: There are many factors influencing postoperative health-related
      quality of life of adolescent idiopathic scoliosis patients, including the degree
      of the deformity, culture, differences in geography, rural versus urban living
      environments, and social factors. The objective of this study was to analyze the
      significance of geographic factors and their differences influencing the
      postoperative quality of life in females with adolescent idiopathic scoliosis
      residing in urban and rural environments, by use of the Polish version of the SRS
      24 questionnaire. MATERIAL/METHODS: Forty urban and 20 rural postoperative
      patients with adolescent scoliosis with a minimum 2-year follow-up period after
      surgery were included in the study. The process of cross-cultural adaptation was
      performed according to the IQOLA Project. RESULTS: General results of the Polish
      SRS-24 equalled 4.1 (SD 0.5) and 4.0 (SD.0.5) in the rural and urban groups of
      patients, respectively. The 2 groups do not differ in incidence of floor and
      ceiling effects. The Cronbach's alpha values are excellent for the general result
      of SRS-24 in urban and rural groups (0.85 and 0.85, respectively). The sub-groups
      differed significantly in the self-image after surgery domain (p=0.048).
      CONCLUSIONS: Patients from the rural group scored higher in the self-image after
      surgery domain but reported higher pain levels when compared to urban patients.
      The associations between SRS-24 results and radiographic parameters in the rural
      group of patients were strong, compared with moderate relations reported in the
      urban group.

PMID- 22847204
TI  - Recurrence of inflammatory myofibroblastic tumor in bladder secondary to prostate
      treated with laparoscopic radical cystectomy.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare borderline tumor.
      The nomenclature of this disease is confused in the literature. CASE REPORT: In
      this report, the case of a 62-year-old man with IMT recurrence of bladder
      secondary to prostate is presented. The possible etiology of IMT is discussed,
      along with its clinical manifestation and pathological features. The patient
      received a laparoscopic bladder radical resection. The pathology finding
      demonstrated the diagnosis of IMT and no regional lymph node involvement.
      CONCLUSIONS: IMT is a borderline tumor and unlikely to metastasize to regional
      lymph nodes. The patient has been observed for 2 years without recurrence.

PMID- 22847205
TI  - Disseminated cutaneous Kaposi sarcoma in a patient receiving
      triptolide/tripdiolide for rheumatoid arthritis.
AB  - BACKGROUND: To date, Kaposi sarcoma has not been mentioned among the adverse
      effects of triptolide/tripdiolide, ethyl acetate extracts or polyglycosides of
      the Chinese herbal remedy Tripterygium wilfordii Hook F. CASE REPORT: A patient
      was diagnosed with rheumatoid arthritis at the age of 29 years. She underwent
      treatment with corticosteroids, methotrexate and gold sodium thiosulfate, and was
      chronically taking ketoprofen. At the age of 59 years she started to take a
      powder (~2 g/day) from a Chinese physician for treatment of rheumatoid arthritis.
      This powder was supplied to her regularly for 10 years. At the age of 69 years,
      multiple soft, violaceous to dark-red patches, plaques, nodules and blisters of
      varying sizes appeared on a background of severely edematous skin on her legs,
      and later on her arms. Biopsy specimens of the leg lesions were diagnostic for
      human herpesvirus 8-associated Kaposi sarcoma. Triptolide (235 ug/1 g) and
      tripdiolide were found in the Chinese powder by the use of Liquid Chromatography
      Electrospray Ionization Mass Spectrometry. Administration of the powder was
      stopped and medication with paclitaxel was introduced. General condition of the
      patient improved and skin lesions diminished significantly. CONCLUSIONS: This
      case indicates a possible association between triptolide/tripdiolide chronic
      intake and development of human herpesvirus 8-associated Kaposi sarcoma.
      Triptolide/tripdiolide could contribute to development of Kaposi sarcoma by
      reactivation of latent human herpesvirus 8, permitted by immunosuppression
      induced by triptolide.

PMID- 22847206
TI  - Lipemia retinalis - an unusual cause of visual acuity deterioration.
AB  - BACKGROUND: Hyperlipidemia is an identified factor of premature vessel
      atherosclerosis. Lipemia retinalis is an unusual retinal manifestation of
      hyperlipidemia and is thought to be directly correlated with the serum
      triglyceride level. CASE REPORT: This paper discusses the case of a 55-year-old
      patient with lipemia retinalis, which deteriorated his visual acuity. The patient
      had an extremely high serum cholesterol level (1053 mg/dl) and a very high level
      of triglycerides (1513 mg/dl). The normalization of serum lipids, reversion of
      retinal vessels alterations and visual acuity improvement was achieved after an
      intensive statin lipid-lowering therapy. Pathological changes of the patient's
      retina, connected with lipemia retinalis, disappeared completely. CONCLUSIONS:
      Hyperlipidemia can cause lipemia retinalis, which is characterized by the
      hyperlipidemic vascular lesions-whitish color of vessels, lipid infiltration into
      the retina and decrease of visual acuity. The lipid-lowering therapy may lead to
      the normalization of the appearance of the fundus and restore the visual acuity.

PMID- 22847207
TI  - Peripheral administration of brain-derived neurotrophic factor to Rett syndrome
      animal model: a possible approach for the treatment of Rett syndrome.
AB  - Rett syndrome (RTT) is a postnatal, severe, disabling neurodevelopmental disorder
      occurring almost exclusively in females and is the second most common cause for
      genetic mental retardation in girls. In the majority of cases it is caused by
      mutations in gene (MECP2) encoding methyl-CpG-binding protein 2. Brain-derived
      neurotrophic factor (BDNF) is a neurotrophic factor playing a major role in
      neuronal survival, neurogenesis and plasticity. Animal studies suggested that
      abnormalities in BDNF homeostasis may contribute to the pathogenesis in Mecp2
      null mice, and BDNF administration in the Mecp2 mutant brain led to later
      onset/slower disease progression, suggesting that increased BDNF in the brain
      could be therapeutic for this disease. Mature BDNF is a 14 kDa protein that may
      have poor blood-brain barrier penetrability. However, recent animal studies
      demonstrated that peripheral administration of BDNF, either by intravenous
      injection or intranasal delivery, could increase BDNF levels in the brain. Thus
      it is proposed that peripheral administration of BDNF in the early stage could
      have therapeutic potential for RTT subjects. Furthermore, the combination use of
      mannitol may temporarily open the blood-brain barrier and facilitate the entry of
      BDNF into brain. The potential therapeutic effect of peripheral BDNF
      administration could be tested in RTT animal models such as Mecp2 KO mice, which
      may provide a new intervention for this devastating disease.

PMID- 22847208
TI  - Transjugular intrahepatic portosystemic shunt may be superior to conservative
      therapy for variceal rebleeding in cirrhotic patients with non-tumoral portal
      vein thrombosis: a hypothesis.
AB  - The presence of occlusive portal vein thrombosis (PVT) greatly changes the
      natural history of liver cirrhosis, because it not only significantly increases
      the incidence of variceal rebleeding but also negatively influences the survival.
      However, due to the absence of strong evidence, no standard treatment algorithm
      for the secondary prophylaxis of variceal bleeding in cirrhotic patients with non
      tumoral PVT has been established. Previous randomized controlled trials have
      demonstrated that transjugular intrahepatic portosystemic shunt (TIPS) can
      significantly decrease the incidence of variceal rebleeding in cirrhotic patients
      without PVT, compared with conservative therapy (i.e., endoscopic plus
      pharmacological therapy). Further, several large cohort studies have confirmed
      that TIPS can effectively prevent variceal rebleeding in cirrhotic patients with
      non-tumoral PVT. On the other hand, TIPS can facilitate recanalizing the
      thrombosed portal vein by endovascular manipulations, even in the presence of
      cavernous transformation of the portal vein (CTPV). More importantly, successful
      TIPS insertions can maintain the persistent portal vein patency, and avoid
      thrombus extension into the portal venous system. By comparison, anticoagulation
      therapy can achieve portal vein recanalization only in patients with partial PVT,
      but not in those with occlusive PVT or CTPV, and the use of anticoagulants may
      aggravate the risk of variceal bleeding in cirrhotic patients with a history of
      variceal bleeding. Collectively, we hypothesize that TIPS may be superior to
      conservative therapy for the prevention of variceal rebleeding in cirrhotic
      patients with non-tumoral PVT. Randomized controlled trials should be conducted
      to evaluate the survival benefit of TIPS in these patients.

PMID- 22847209
TI  - A novel bionic design of dental implant for promoting its long-term success using
      nerve growth factor (NGF): utilizing nano-springs to construct a stress
      cushioning structure inside the implant.
AB  - The absence of periodontium causes masticatory load in excess of the self
      repairing potential of peri-implant bone; peri-implant bone loss caused by
      occlusal overload is not uncommon in patients and greatly diminishes chances of
      long-term success. Regenerative treatments may be useful in inducing peri-implant
      bone regeneration, but are only stopgap solutions to the aftermaths caused by the
      imperfect biomechanical compatibility of the dental implant. Despite promising
      success, the tissue-engineered periodontal ligament still needs a period of time
      to be perfected before being clinically applied. Hence, we propose a novel design
      of dental implant that utilizes nano-springs to construct a stress-cushioning
      structure inside the implant. Many studies have shown that NGF, a neurotrophin,
      is effective for nerve regeneration in both animal and clinical studies.
      Moreover, NGF has the potential to accelerate bone healing in patients with
      fracture and fracture nonunion and improve osseointegration of the implant. The
      key point of the design is to reduce stress concentrated around peri-implant bone
      by cushioning masticatory forces and distributing them to all the peri-implant
      bone through nano-springs, and promote osseoperception and osseointegration by
      NGF-induced nerve regeneration and new bone formation. This design, which
      transfers the main biomechanical interface of the implant from outside to inside,
      if proven to be valid, may to some extent compensate for the functions of lost
      periodontium in stress cushioning and proprioception.

PMID- 22847210
TI  - A novel hypothesis: the application of platelet-rich plasma can promote the
      clinical healing of white-white meniscal tears.
AB  - The white-white tears (meniscus lesion completely in the avascular zone) are
      without blood supply and theoretically cannot heal. Basal research has
      demonstrated that menisci are unquestionably important in load bearing, load
      redistribution, shock absorption, joint lubrication and the stabilization of the
      knee joint. It has been proven that partial or all-meniscusectomy results in an
      accelerated degeneration of cartilage and an increased rate of early
      osteoarthritis. Knee surgeons must face the difficult decision of removing or, if
      possible, retaining the meniscus; if it is possible to retain the meniscus,
      surgeons must address the difficulties of meniscal healing. Some preliminary
      approaches have progressed to improve meniscal healing. However, the problem of
      promoting meniscal healing in the avascular area has not yet been resolved. The
      demanding nature of the approach as well as its low utility and efficacy has
      impeded the progress of these enhancement techniques. Platelet-rich plasma (PRP)
      is a platelet concentration derived from autologous blood. In recent years, PRP
      has been used widely in preclinical and clinical applications for bone
      regeneration and wound healing. Therefore, we hypothesize that the application of
      platelet-rich plasma for white-white meniscal tears will be a simple and novel
      technique of high utility in knee surgery.

PMID- 22847211
TI  - The relation of sTRAIL levels and quality of life in severe persistent allergic
      asthma patients using omalizumab.

PMID- 22847212
TI  - Do patients with active RA have differences in disease activity and perceptions
      if anti-TNF naive versus anti-TNF experienced? Baseline results of the
      optimization of adalimumab trial.
AB  - BACKGROUND: The chance of a good response in RA is attenuated in previous anti
      TNF users who start new anti-TNF therapy compared to biologic naive patients. In
      active RA, those with previous anti-TNF exposure compared to anti-TNF naive may
      have different baseline disease activity and patient perceptions when starting a
      new anti-TNF treatment that could explain the observed response differences.
      MATERIAL/METHODS: The aim of this study was a post hoc analysis of baseline
      characteristics of patients enrolled in the Optimization of Adalimumab study that
      was a treat to target vs. routine care study in patients initiating adalimumab.
      As per the protocol, a maximum of 20% anti-TNF experienced patients were enrolled
      in the 300 patient trial. Twelve (4.0%) were excluded who previously used other
      biologics. Baseline characteristics including age, gender, tender and swollen
      joint counts, disease activity (DAS28), function (HAQ-DI), patient global
      assessment, patient satisfaction with current treatment, and inflammatory markers
      (CRP, ESR), were compared between previously anti-TNF experienced [etanercept or
      infliximab (EXP)], and anti-TNF naive patients (NAIVE). RESULTS: The mean (SD)
      age was 54.8 (13.3) years; 81.0% were female, and 237 (79.0%) were anti-TNF naive
      while 51 (17.0%) patients were anti-TNF experienced (29 with etanercept, 16 with
      infliximab, and 6 for both). The mean (SD) baseline in EXP versus NAIVE groups
      respectively was: CRP=21.7(32.9) vs. 17.5(20.7); ESR=28.7(22.5) vs. 29.8(20.4);
      SJC=10.5(6.0) vs. 10.7(5.6); TJC=12.8(7.1) vs. 12.3(7.3); and DAS28=6.0(1.2) vs.
      5.8(1.1). None of the between-group differences were statistically significant,
      however, the HAQ-DI in EXP was 1.7(0.6) compared to 1.5(0.7) for the NAIVE
      (P=0.021). Additionally, EXP patients had a higher patient global score
      [71.3(26.1) vs. 61.9(26.2), P=0.021]. CONCLUSIONS: Although anti-TNF naive and
      experienced patients who initiated adalimumab were similar, with respect to
      several baseline characteristics, significant differences in subjective measures
      were observed, which may indicate more severe patient measures (function and
      global disease activity) in anti-TNF experienced patients.

PMID- 22847213
TI  - Dietary selenium and selenoprotein function.
AB  - Selenium is a trace mineral and an essential nutrient in the human diet. Selenium
      is found in soil and water and consequently enters the food chain through the
      root ways of plants and aquatic organisms. Some areas of the world are low in
      soil selenium resulting in a selenium deficient population and the appearance of
      an associated heart disease and bone disorders that can be corrected with dietary
      selenium. Indeed the requirement for dietary selenium was established by these
      observations and while selenium deficiency is rare in the West, patients
      requiring long-term intravenous feedings have also show heart disease associated
      with a deficiency of selenium in the feeding fluids. Subsequently, it has been
      established that dietary selenium can improve a wide range of human health
      conditions even in areas with soil replete in selenium.

PMID- 22847215
TI  - Ocular ischemic syndrome - a systematic review.
AB  - Ocular ischemic syndrome is a rare condition, which is caused by ocular
      hypoperfusion due to stenosis or occlusion of the common or internal carotid
      arteries. Atherosclerosis is the major cause of changes in the carotid arteries.
      Ocular ischemic syndrome is manifested as visual loss, orbital pain and,
      frequently, changes of the visual field, and various anterior and posterior
      segment signs. Anterior segment signs include iris neovascularization and
      secondary neovascular glaucoma, iridocyclitis, asymmetric cataract, iris atrophy
      and sluggish reaction to light. Posterior eye segment changes are the most
      characteristic, such as narrowed retinal arteries, perifoveal telangiectasias,
      dilated retinal veins, mid-peripheral retinal hemorrhages, microaneurysms,
      neovascularization at the optic disk and in the retina, a cherry-red spot, cotton
      wool spots, vitreous hemorrhage and normal-tension glaucoma. Differential
      diagnosis of ocular ischemic syndrome includes diabetic retinopathy and moderate
      central retinal vein occlusion. Carotid artery imaging and fundus fluorescein
      angiography help to establish the diagnosis of ocular ischemic syndrome. The
      treatment can be local, for example, ocular (conservative, laser and surgical) or
      systemic (conservative and surgical treatment of the carotid artery). Since the
      condition does not affect the eyes alone, patients with ocular ischemic syndrome
      should be referred for consultation to the neurologist, vascular surgeon and
      cardiologist.

PMID- 22847214
TI  - Parkinson's disease, L-DOPA, and endogenous morphine: a revisit.
AB  - Clinical observations stemming from widespread employment of restorative L-3,4
      dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in
      Parkinson's Disease (PD) patients implicate a regulatory role for endogenous
      morphine in central nervous system dopamine neurotransmission. Reciprocally, it
      appears that restorative L-DOPA administration has provided us with a compelling
      in vivo pharmacological model for targeting peripheral sites involved in
      endogenous morphine expression in human subjects. The biological activities
      underlying endogenous morphine expression and its interaction with its major
      precursor dopamine strongly suggest that endogenous morphine systems are
      reciprocally dysregulated in PD. These critical issues are examined from
      historical and current perspectives within our short review.

PMID- 22847216
TI  - Involvement of the cAMP response element binding protein, CREB, and cyclin D1 in
      LPA-induced proliferation of P19 embryonic carcinoma cells.
AB  - Lysophosphatidic acid (LPA) is a lipid growth factor that induces proliferation
      of fibroblasts by activating the cAMP response element binding protein (CREB).
      Here, we further investigated whether LPA induces proliferation of P19 cells, a
      line of pluripotent embryonic carcinoma cells. 5'-Bromo-2-deoxyuridine
      incorporation and cell viability assays showed that LPA stimulated proliferation
      of P19 cells. Immunoblot experiments with P19 cells revealed that the mitogen
      activated protein kinases, including p-ERK, p38, pAKT, glycogen synthase kinase
      3beta, and CREB were phosphorylated by treatment with 10 MUM LPA. LPA-induced
      phosphorylation of CREB was efficiently blocked by U0126 and H89, inhibitors of
      the MAP kinases ERK1/2 and mitogen- and stress-activated protein kinase 1,
      respectively. Involvement of cyclin D1 in LPA-induced P19 cell proliferation was
      verified by immunoblot analysis in combination with pharmacological inhibitor
      treatment. Furthermore, LPA up-regulated CRE-harboring cyclin D1 promoter
      activity, suggesting that CREB and cyclin D1 play significant roles in LPA
      induced proliferation of P19 embryonic carcinoma cells.

PMID- 22847217
TI  - LSI-based amperometric sensor for bio-imaging and multi-point biosensing.
AB  - We have developed an LSI-based amperometric sensor called "Bio-LSI" with 400
      measurement points as a platform for electrochemical bio-imaging and multi-point
      biosensing. The system is comprised of a 10.4 mm * 10.4 mm CMOS sensor chip with
      20 * 20 unit cells, an external circuit box, a control unit for data acquisition,
      and a DC power box. Each unit cell of the chip contains an operational amplifier
      with a switched-capacitor type I-V converter for in-pixel signal amplification.
      We successfully realized a wide dynamic range from +/-1 pA to +/-100 nA with a
      well-organized circuit design and operating software. In particular, in-pixel
      signal amplification and an original program to control the signal read-out
      contribute to the lower detection limit and wide detection range of Bio-LSI. The
      spacial resolution is 250 MUm and the temporal resolution is 18-125 ms/400
      points, which depends on the desired current detection range. The coefficient of
      variance of the current for 400 points is within 5%. We also demonstrated the
      real-time imaging of a biological molecule using Bio-LSI. The LSI coated with an
      Os-HRP film was successfully applied to the monitoring of the changes of hydrogen
      peroxide concentration in a flow. The Os-HRP-coated LSI was spotted with glucose
      oxidase and used for bioelectrochemical imaging of the glucose oxidase (GOx)
      catalyzed oxidation of glucose. Bio-LSI is a promising platform for a wide range
      of analytical fields, including diagnostics, environmental measurements and basic
      biochemistry.

PMID- 22847219
TI  - Comparison of vertical and adiabatic harmonic approaches for the calculation of
      the vibrational structure of electronic spectra.
AB  - The calculation of the vibrational structure associated to electronic spectra in
      large molecules requires a Taylor expansion of the initial and final state
      potential energy surface (PES) around some reference nuclear structure. Vertical
      (V) and adiabatic (A) approaches expand the final state PES around the initial
      state (V) or final-state (A) equilibrium structure. Simplest models only take
      into account displacements of initial- and final-state minima, intermediate ones
      also allow for difference in frequencies and more accurate models introduce the
      Dushinsky effect through the computation of the Hessians of both the initial and
      final state. In this contribution we summarize and compare the mathematical
      expressions of the complete hierarchy of V and A harmonic models and we implement
      them in a numerical code, presenting a detailed comparison of their performance
      on a number of prototypical systems. We also address non-Condon effects through
      linear expansions of the transition dipole as a function of nuclear coordinates
      (Herzberg-Teller effect) and compare the results of expansions around initial and
      final state equilibrium geometries. By a throughout analysis of our results we
      highlight a number of general trends in the relative performance of the models
      that can provide hints for their proper choice. Moreover we show that A and V
      models including final state PES Hessian outperform the simpler ones and that
      discrepancies in their predictions are diagnostic for failure of harmonic
      approximation and/or of Born-Oppenheimer approximation (existence of remarkable
      geometry-dependent mixing of electronic states).

PMID- 22847218
TI  - Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60
      years after exposure.
AB  - Thyroid cancer risk following exposure to ionizing radiation in childhood and
      adolescence is a topic of public concern. To characterize the long-term temporal
      trend and age-at-exposure variation in the radiation-induced risk of thyroid
      cancer, we analyzed thyroid cancer incidence data for the period from 1958
      through 2005 among 105,401 members of the Life Span Study cohort of Japanese
      atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases
      (excluding those with microcarcinoma with a diameter <10 mm) were identified as a
      first primary among the eligible subjects. Using a linear dose-response model,
      the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was
      estimated as 1.28 (95% confidence interval: 0.59-2.70) at age 60 after acute
      exposure at age 10. The risk decreased sharply with increasing age-at-exposure
      and there was little evidence of increased thyroid cancer rates for those exposed
      after age 20. About 36% of the thyroid cancer cases among those exposed before
      age 20 were estimated to be attributable to radiation exposure. While the
      magnitude of the excess risk has decreased with increasing attained age or time
      since exposure, the excess thyroid cancer risk associated with childhood exposure
      has persisted for >50 years after exposure.

PMID- 22847220
TI  - Effects of aripiprazole and its active metabolite dehydroaripiprazole on the
      activities of drug efflux transporters expressed both in the intestine and at the
      blood-brain barrier.
AB  - The inhibition potencies of aripiprazole and its active metabolite,
      dehydroaripiprazole, on the activities of human multidrug resistance protein 1
      (MDR1/ABCB1; P-glycoprotein), breast cancer resistance protein (BCRP/ABCG2) and
      multidrug resistance-associated protein 4 (MRP4/ABCC4), that are drug efflux
      transporters expressed both in the intestine and at the blood-brain barrier
      (BBB), were investigated. Aripiprazole and dehydroapripiprazole showed relatively
      strong inhibitory effects on human MDR1 with IC(50) values of 1.2 and 1.3 um in
      human MDR1-transfected Mardin-Darby canine kidney (MDCKII-MDR1) cells,
      respectively. The inhibition potencies of other atypical antipsychotics
      (risperidone, paliperidone, olanzapine and ziprasidone) for human MDR1 were also
      evaluated using the same in vitro experimental system and IC(50) values were more
      than 10-fold higher than those of the two compounds. Aripiprazole and
      dehydroaripiprazole also had inhibition potencies against human BCRP with IC(50)
      values of 3.5 and 0.52 um, respectively. The ratios of steady-state unbound
      concentrations of aripiprazole and dehydroaripiprazole to their IC(50) values
      against human MDR1 and BCRP activities were less than 0.1, whereas the
      theoretically maximum gastrointestinal concentration of aripiprazole ([I](2) ) to
      its IC(50) values was much higher than the cut-off value of 10, proposed by the
      International Transporter Consortium (ITC) and the Food and Drug Administration
      (FDA). In contrast, aripiprazole and dehydroaripiprazole showed almost no
      inhibitory effect against the activity of human MRP4. These findings indicate
      that aripiprazole is unlikely to cause drug-drug interactions (DDIs) at the BBB
      when co-administered with substrate drugs of these drug transporters
      investigated. However, interactions at the intestinal absorption process may be
      of concern.

PMID- 22847221
TI  - Transpulmonary pressure targets for open lung and protective ventilation: one
      size does not fit all.

PMID- 22847223
TI  - Reliability and validity of a kinematic spine model during active trunk movement
      in healthy subjects and patients with chronic non-specific low back pain.
AB  - OBJECTIVE: To develop a standardized, reliable, valid spine model of active trunk
      movements that accurately discriminates kinematic patterns of patients with
      chronic non-specific low back pain from those of healthy subjects. DESIGN:
      Comparative cohort study. SUBJECTS: Healthy subjects (n = 25) and patients with
      chronic non-specific low back pain (n = 25) aged 30-65 years. METHODS: Subjects
      performed 7 trunk movements from a seated position at non-imposed speed during 2
      sessions. Nine markers on bony landmarks measured range of motion and speed of 5
      spinal segments, recorded by 8 optoelectronic cameras. RESULTS: Both groups
      showed good-excellent reliability in all movements for range of motion and speed
      of all spinal segments (intraclass correlation (ICC), 0.70-0.96; standard error
      of measurement, expressed as a percentage, 19.4-3.3%). The minimal detectable
      change in the patient group was 16.7-53.7%. Range of motion and speed in all
      spinal segments for trunk flexion, rotation, and flexion with rotation differed
      significantly between groups (p < 0.001), with large/very large effect sizes
      (Cohen's d = 1.2-2). Binary logistic regression yielded
      sensitivities/specificities of 92%/84% for range of motion and 92%/80% for speed.
      CONCLUSION: Kinematic variables are valid, reliable measures and can be used
      clinically to diagnose chronic non-specific low back pain, manage treatment, and
      as quantitative outcome measures for clinical trial interventions.

PMID- 22847224
TI  - The influence of participation, gender and organizational sense of community on
      psychological empowerment: the moderating effects of income.
AB  - This study explored the influence of participation, gender and organizational
      sense of community (SOC) on both the intrapersonal and interactional components
      of psychological empowerment (PE). Participants were residents (n = 562) involved
      in community organizing efforts in five U.S. communities. Measures of
      participation and SOC were tailored to community organization contexts. SOC
      assessed three dimensions: (1) connection of members to the organization; (2)
      perceptions about the organization as a bridge to other groups and organizations
      in the broader community; and (3) bond or attachment to the community at large.
      Income (low, middle and high-income) was tested as a moderator of these
      relationships. Results showed significant moderating effects of income on the
      relationship between participation, gender and SOC on both components of PE.
      Participation was positively related with intrapersonal empowerment across income
      levels, but positively related with interactional empowerment only for low-income
      individuals. Gender was only associated with intrapersonal empowerment, and only
      for low-income individuals. SOC, as expressed through bridging to the broader
      community, was positively related with interactional PE for all income levels,
      but with intrapersonal PE for only low and middle-income individuals. In
      contrast, member connection to the organization was not related to interactional
      empowerment and significantly related to intrapersonal empowerment only for
      individuals with higher income. The importance of participation, gender and SOC
      for different types of empowerment and the impact of income on the SOC
      empowerment relationship are discussed.

PMID- 22847225
TI  - A multi-professional UK wide survey of undergraduate continence education.
AB  - OBJECTIVES: Findings from national audits and enquiries continue to report that
      care for patients with continence problems is often substandard and inadequate
      education is often cited as one of the probable causes. These factors combined
      with the forecasted increase in the number of people with incontinence prompted
      us to undertake a survey of all UK Higher Education Institutes (HEIs) to
      establish the amount of undergraduate continence education within relevant
      healthcare programs--medical, adult nursing, mental health nursing, learning
      disabilities nursing, children's nursing, midwifery, physiotherapy, and
      occupational therapy. DESIGN: An on line questionnaire targeted course program
      leads (n = 362) in all 86 HEIs in which undergraduate professional healthcare
      programs were provided (n = 362). MAIN OUTCOME MEASURE: Eighty-six HEIs were
      approached, 85 agreed to participate in the survey. A response rate of 81% (n =
      294/362 programs) was obtained: 14% (n = 42) of respondents reported that there
      was no continence-related education within their undergraduate program. The mean
      number of hours was 4.7 (SD 4.3), and ranged from 2.5 (SD 3.5) hr (Occupational
      Therapy) to 7.3 (SD 4.8) hr (Adult Nursing). CONCLUSION: The survey results
      indicate that the amount of undergraduate education has changed little. Further
      research is needed to identify the most appropriate methods of delivering
      continence education and translate knowledge into improved patient outcomes.
      Adequate undergraduate continence education directed by the General Medical
      Council, Royal Colleges and Health Professional Council is required.

PMID- 22847226
TI  - Roseibacterium beibuensis sp. nov., a novel member of roseobacter clade isolated
      from Beibu Gulf in the South China Sea.
AB  - A novel aerobic, bacteriochlorophyll-containing bacteria strain JLT1202r(T) was
      isolated from Beibu Gulf in the South China Sea. Cells were gram-negative, non
      motile, and short-ovoid to rod-shaped with two narrower poles. Strain JLT1202r(T)
      formed circular, opaque, wine-red colonies, and grew optimally at 3-4 % NaCl, pH
      7.5-8.0 and 28-30  degrees C. The strain was catalase, oxidase, ONPG, gelatin,
      and Voges-Proskauer test positive. In vivo absorption spectrum of
      bacteriochlorophyll a presented two peaks at 800 and 877 nm. The predominant
      cellular fatty acid was C(18:1) omega7c and significant amounts of C(16:0),
      C(18:0), C(10:0) 3-OH, C(16:0) 2-OH, and 11-methyl C(18:1) omega7c were present.
      Strain JLT1202r(T) contained Q-10 as the major respiratory quinone and the
      genomic DNA G+C content was 76.3 mol%. Phylogenetic analysis based on 16S rRNA
      gene sequences of various species with validly published names showed that strain
      JLT1202r(T) fell within the genus Roseibacterium, family Rhodobacteraceae,
      sharing the highest similarity with Roseibacterium elongatum OCh 323(T) (97.9 %
      similarity), followed by Dinoroseobacter shibae DFL 12(T) (95.4 % similarity).
      The phylogenetic distance of pufM genes between strain JLT1202r(T) and R.
      elongatum OCh 323(T) was 9.4 %, suggesting that strain JLT1202r(T) was distinct
      from the only strain of the genus Roseibacterium. Based on the variabilities of
      phylogenetic and phenotypic characteristics, strain JLT1202r(T) stands for a
      novel species of the genus Roseibacterium and the name R. beibuensis sp. nov. is
      proposed with JLT1202r(T) as the type strain (=JCM 18015(T) = CGMCC 1.10994(T)).

PMID- 22847227
TI  - Screening for coronary heart disease with electrocardiography: U.S. Preventive
      Services Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 2004 U.S. Preventive Services Task Force (USPSTF)
      recommendation statement on screening for coronary heart disease (CHD). METHODS:
      The USPSTF reviewed new evidence on the benefits of screening with
      electrocardiography (ECG) in asymptomatic adults to reduce the risk for CHD
      events versus not screening, the effect of identifying high-risk persons on
      treatment to reduce risk, the accuracy of stratifying individuals into risk
      categories, and the harms of screening. RECOMMENDATIONS: The USPSTF recommends
      against screening with resting or exercise ECG for the prediction of CHD events
      in asymptomatic adults at low risk for CHD events (D recommendation). The USPSTF
      concludes that the current evidence is insufficient to assess the balance of
      benefits and harms of screening with resting or exercise ECG for the prediction
      of CHD events in asymptomatic adults at intermediate or high risk for CHD events
      (I statement).

PMID- 22847228
TI  - Assessment of occupational exposure among pakistani medical staff during 2007
      2011.
AB  - The data analysis of occupationally exposed medical workers in Nuclear Medicine
      (NM), Radiotherapy (RT) and Diagnostic Radiology (DR) at the Institute of Nuclear
      Medicine and Oncology (INMOL), Pakistan is presented for the time interval (2007
      2011). The whole-body exposure doses of the workers were measured by using the
      Film Badge Dosimetry technique. The annual average effective doses in NM, RT and
      DR have been found well below the permissible annual limit of 20 mSv (averaged
      over a period of 5 consecutive years), with no over-exposure detected. This
      declining trend of annual average effective dose is the consequence of improved
      radiation protection practices at INMOL during the recent years.

PMID- 22847229
TI  - Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal
      neurons from SV2A-deficient but not SV2B-deficient mice.
AB  - Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms,
      SV2A, SV2B, and SV2C. SV2A knockout (KO) mice and SV2A/SV2B double KO (DKO) mice,
      but not SV2B KO animals, start to experience severe seizures and weight loss 7
      days after birth and die at about postnatal day (P)14-P23. Because excitatory and
      inhibitory inputs play a major role in controlling neuronal excitability in the
      hippocampus, we examined the effects of SV2A and/or SV2B deletions on
      glutamatergic and GABA(A) neurotransmission in hippocampal CA1 pyramidal neurons.
      Spontaneous and miniature excitatory and inhibitory postsynaptic currents
      (sEPSCs, mEPSCs, sIPSCs, and mIPSCs, respectively) were recorded using the whole
      cell patch-clamp technique in slices from P6-P14 mice. The frequency of sEPSCs
      was increased in SV2A KO and SV2A/SV2B DKO mice, but their amplitude was
      unchanged. Such changes were not observed in SV2B KOs. On the contrary, the
      frequency and amplitude of sIPSCs were decreased in SV2A KO and SV2A/SV2B DKO
      mice but not in SV2B KO animals, as reported previously for the CA3 region.
      Kinetic parameters of sIPSCs and sEPSCs were unchanged. Importantly, no changes
      were observed in any genotype when examining mEPSCs and mIPSCs. We conclude that
      action potential- and Ca(2+) -dependent glutamatergic and GABAergic synaptic
      transmission are differentially altered in the hippocampus of SV2A-deficient
      mice, whereas the mechanism of exocytosis itself is not changed. The altered
      balance between these major excitatory and inhibitory inputs is probably a
      contributing factor to seizures in SV2A KO and SV2A/SV2B DKO mice.

PMID- 22847230
TI  - Development and validation of a rapid RP-HPLC method for analysis of (-)-copalic
      acid in copaiba oleoresin.
AB  - The Copaifera species (Leguminoseae) are popularly known as 'copaiba' or
      'copaiva' and are grown in the states of Amazonas, Para and Ceara in northern
      Brazil. The oleoresins obtained from these species have been extensively used
      owing to their pharmacological potential and their application in cosmetic and
      pharmaceutical preparations. In the present study, the development and validation
      of a novel, rapid and efficient RP-HPLC methodology for the analysis of the
      diterpene (-)-copalic acid (CA), pointed out as the only chemical marker of the
      Copaifera genus, are described. The regression equation (Y = 26,707x - 29,498)
      was obtained with good linearity (r(2) = 0.9993) and the limits of quantification
      and detection were 9.182 and 3.032 ug/mL, respectively. The precision and the
      accuracy of the method were adequate (lower than 4%). Finally, the validation
      parameters evaluated were satisfactorily met, so the developed method represents
      a suitable tool for application in the quality control of such natural products.
      Further studies aiming to develop analytical methodologies for each Copaifera
      species using a more representative number of chemical markers should be
      performed.

PMID- 22847231
TI  - Identification of heat shock protein 27 as a radioresistance-related protein in
      nasopharyngeal carcinoma cells.
AB  - PURPOSE: To identify the proteins involved in radioresistance in nasopharyngeal
      cancer (NPC) cells. METHODS: Sublethal ionizing radiation was applied to
      establish a radioresistant NPC cell line from its parental NPC cell line CNE1.
      Clonogenic survival assay, cell growth assay and flow cytometry analysis were
      used to examine the difference of radiosensitivity in the radioresistant CNE1
      cells (CNE1-IR) and control CNE1 cells. Comparative proteomics was performed to
      identify the differential proteins in the two cell lines. Association of HSP27,
      one of upregulated proteins in CNE1-IR cells, with NPC cell radioresistance was
      selected for further investigation using antisense oligonucleotides (ASOs),
      clonogenic survival assay, Hoechst 33258 staining of apoptotic cells and MTT
      assay of cell viability. RESULTS: Radioresistant NPC cell line CNE1-IR derived
      from its parental cell line CNE1 was established. Thirteen differential proteins
      in the CNE1-IR and CNE1 cells were identified by proteomics, and differential
      expression of HSP27, one of identified proteins, was selectively confirmed by
      western blot. Inhibition of HSP27 expression by HSP27 ASOs decreased clonogenic
      survival and cell viability and increased cell apoptosis of CNE1-IR cells after
      irradiation, that is, enhanced radiosensitivity of CNE1-IR cells. CONCLUSION: The
      data suggest that HSP27 is a radioresistant protein in NPC cells, and its
      upregulation may be involved in the NPC radioresistance.

PMID- 22847232
TI  - Novel approach to generate genetically engineered, sortable, DeltaNGFR-tagged
      mouse Th17 cells.
AB  - T helper (Th) 17 cells are difficult to isolate which hinders experimental
      studies with these cells. Here, we report a novel method to obtain sortable,
      engineered mouse Th17 cells. First, we developed lentiviral vector (XZ12)
      containing RORgammat gene and mouse DeltaNGFR gene complemented with IL17A
      promoter (pXZ12-RORgammat). As control, we used vector pXZ12 containing mouse
      DeltaNGFR gene complemented with IL17A promoter. Mouse CD4(+)CD25(-) T cells were
      transduced with pXZ12-RORgammat or pXZ12 vectors and cultured in the presence of
      transforming growth factor (TGF)-beta or interleukin (IL)-6. Then, we isolated
      Th17 cells using anti-DeltaNGFR magnetic beads. The cytokine production profiles
      of isolated Th17 cells were assessed by qPCR, while cell functional capabilities
      tested in an experimental model of mouse autoimmune encephalomyelitis (EAE). We
      observed that overexpression of RORgammat in the presence of TGF-beta and IL-6 is
      highly efficient to produce Th17 cells. After sorting, the purity of IL-17A(+)
      population was over 90 %. The phenotype of pXZ12-RORgammat transduced cells in
      the presence of TGF-beta and IL-6 was similar to natural Th17 cells, in contrast
      to cells overexpressing RORgammat alone which were deficient for IL-21. The
      engineered Th17 cells intensified EAE in C57BL6 mice indicating that these cells
      were phenotypically and functionally similar to natural Th17 cells. In
      conclusion, the engineered Th17 cells described here can be a useful tool to
      advance studies on Th17 cells.

PMID- 22847233
TI  - Discontinuous molecular dynamics (DMD) study of heteropolymer collapse in an
      explicit solvent.
AB  - In this study, we employ the discontinuous molecular dynamics simulation method
      to investigate the collapse properties of a single heteropolymer chain in an
      explicit solvent. Solvent density rho, fraction of hydrophobic monomers n H
      (defined as the ratio of the number of hydrophobic monomers to the total number
      of monomers) and a hydrophobicity parameter lambda (which controls the energy
      mismatch between the monomers and solvent particles) were systematically varied
      to examine their role in polymer collapse. The average static structure factor of
      the polymer was used to find the so-called theta-point characterizing the state
      of an ideal chain. Phase diagrams of rho versus lambda for the coil-globule
      transition were mapped out for different values of n H. Increasing the fraction
      of hydrophobic monomers n H, solvent density rho, and hydrophobicity parameter
      lambda were all shown to aid in stabilizing the globule phase. In an effort to
      explore scaling behaviour of the coil-globule phase diagram as a function of n H,
      and to investigate whether the phase boundaries for different n H collapsed on to
      one universal curve, we rescaled lambda by n H (delta) lambda; we determined
      delta = 1.72, in contrast to mean-field predictions of delta = 2.0.

PMID- 22847234
TI  - Comparative expression profiling identifies differential roles for Myogenin and
      p38alpha MAPK signaling in myogenesis.
AB  - Skeletal muscle differentiation is mediated by a complex gene expression program
      requiring both the muscle-specific transcription factor Myogenin (Myog) and
      p38alpha MAPK (p38alpha) signaling. However, the relative contribution of Myog
      and p38alpha to the formation of mature myotubes remains unknown. Here, we have
      uncoupled the activity of Myog from that of p38alpha to gain insight into the
      individual roles of these proteins in myogenesis. Comparative expression
      profiling confirmed that Myog activates the expression of genes involved in
      muscle function. Furthermore, we found that in the absence of p38alpha signaling,
      Myog expression leads to the down-regulation of genes involved in cell cycle
      progression. Consistent with this, the expression of Myog is sufficient to induce
      cell cycle exit. Interestingly, p38alpha-defective, Myog-expressing myoblasts
      fail to form multinucleated myotubes, suggesting an important role for p38alpha
      in cell fusion. Through the analysis of p38alpha up-regulated genes, the
      tetraspanin CD53 was identified as a candidate fusion protein, a role confirmed
      both ex vivo in primary myoblasts, and in vivo during myofiber regeneration in
      mice. Thus, our study has revealed an unexpected role for Myog in mediating cell
      cycle exit and has identified an essential role for p38alpha in cell fusion
      through the up-regulation of CD53.

PMID- 22847236
TI  - Chronic potentiation of cardiac L-type Ca(2+) channels by pirfenidone.
AB  - AIMS: On the basis of its ability to inhibit fibrosis, pirfenidone has drawn the
      attention as an intriguing candidate for treating cardiac disease. However, its
      precise electrophysiological effects have yet to be elucidated. Here, we have
      investigated its potential to modulate ion channels. METHODS AND RESULTS: Adult
      rat cardiac myocytes were investigated using whole-cell patch-clamp, western-blot
      and qRT-PCR techniques. Pirfenidone increased the density of L-type Ca(2+)
      current (I(CaL,) 50-100%), without significantly altering Na(+), K(+), or T-type
      Ca(2+) currents. The effect was dose-dependent, with an EC(50) of 2.8 uM. Its
      onset was slow, with a lag period larger than 1 h and time to maximum of 24-48 h.
      Concomitant changes were observed in the voltage-dependent activation of I(CaL) (
      5 mV shift in both V(1/2) and k). In contrast, the following properties of I(CaL)
      remained normal: steady-state inactivation, Ca(V)1.2 levels (mRNA and protein),
      and intramembrane charge movement. Indeed, the conductance-to-charge ratio, or
      G(max)/Q(max), was increased by 80%. The effect on I(CaL) was mimicked by an
      inhibitor of nitric oxide (NO) synthase (NOS), and attenuated by both cyclic
      adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA)
      inhibitors. Conversely, cytokines, reactive oxygen species, and Ca(2+) were all
      ruled out as possible intermediaries. Additional experiments suggest that
      pirfenidone increases action potential duration by ~50%. CONCLUSION: Pirfenidone
      augments I(CaL), not through higher expression of L-type channels, but through
      promoting their Ca(2+)-conducting activity. A possible inhibition of NOS
      expression is likely involved, with subsequent reduced NO production and
      stimulated cAMP/PKA signalling. These findings may be relevant to the
      cardioprotective effect of pirfenidone.

PMID- 22847235
TI  - Endometrial regeneration and endometrial stem/progenitor cells.
AB  - The functional layer of the human endometrium is a highly regenerative tissue
      undergoing monthly cycles of growth, differentiation and shedding during a
      woman's reproductive years. Fluctuating levels of circulating estrogen and
      progesterone orchestrate this dramatic remodeling of human endometrium. The thin
      inactive endometrium of postmenopausal women which resembles the permanent basal
      layer of cycling endometrium retains the capacity to respond to exogenous sex
      steroid hormones to regenerate into a thick functional endometrium capable of
      supporting pregnancy. Endometrial regeneration also follows parturition and
      endometrial resection. In non menstruating rodents, endometrial epithelium
      undergoes rounds of proliferation and apoptosis during estrus cycles. The recent
      identification of adult stem cells in both human and mouse endometrium suggests
      that epithelial progenitor cells and the mesenchymal stem/stromal cells have key
      roles in the cyclical regeneration of endometrial epithelium and stroma. This
      review will summarize the evidence for endometrial stem/progenitor cells, examine
      their role in mouse models of endometrial epithelial repair and estrogen-induced
      endometrial regeneration, and also describe the generation of endometrial-like
      epithelium from human embryonic stem cells. With markers now available for
      identifying endometrial mesenchymal stem/stromal cells, their possible role in
      gynecological diseases associated with abnormal endometrial proliferation and
      their potential application in cell-based therapies to regenerate reproductive
      and other tissues will be discussed.

PMID- 22847238
TI  - Thyroid cancer: Pazopanib alone is not effective against anaplastic thyroid
      cancer.

PMID- 22847237
TI  - Candida albicans biofilm chip (CaBChip) for high-throughput antifungal drug
      screening.
AB  - Candida albicans remains the main etiological agent of candidiasis, which
      currently represents the fourth most common nosocomial bloodstream infection in
      US hospitals. These opportunistic infections pose a growing threat for an
      increasing number of compromised individuals, and carry unacceptably high
      mortality rates. This is in part due to the limited arsenal of antifungal drugs,
      but also to the emergence of resistance against the most commonly used antifungal
      agents. Further complicating treatment is the fact that a majority of
      manifestations of candidiasis are associated with the formation of biofilms, and
      cells within these biofilms show increased levels of resistance to most
      clinically-used antifungal agents. Here we describe the development of a high
      density microarray that consists of C. albicans nano-biofilms, which we have
      named CaBChip. Briefly, a robotic microarrayer is used to print yeast cells of C.
      albicans onto a solid substrate. During printing, the yeast cells are enclosed in
      a three dimensional matrix using a volume as low as 50 nL and immobilized on a
      glass substrate with a suitable coating. After initial printing, the slides are
      incubated at 37  degrees C for 24 hours to allow for biofilm development. During
      this period the spots grow into fully developed "nano-biofilms" that display
      typical structural and phenotypic characteristics associated with mature C.
      albicans biofilms (i.e. morphological complexity, three dimensional architecture
      and drug resistance). Overall, the CaBChip is composed of ~750 equivalent and
      spatially distinct biofilms; with the additional advantage that multiple chips
      can be printed and processed simultaneously. Cell viability is estimated by
      measuring the fluorescent intensity of FUN1 metabolic stain using a microarray
      scanner. This fungal chip is ideally suited for use in true high-throughput
      screening for antifungal drug discovery. Compared to current standards (i.e. the
      96-well microtiter plate model of biofilm formation), the main advantages of the
      fungal biofilm chip are automation, miniaturization, savings in amount and cost
      of reagents and analyses time, as well as the elimination of labor intensive
      steps. We believe that such chip will significantly speed up the antifungal drug
      discovery process.

PMID- 22847240
TI  - Diabetes: normal glucose levels should be the goal.

PMID- 22847239
TI  - Adaptive immunity in obesity and insulin resistance.
AB  - Obesity is the hallmark of the metabolic syndrome and predisposes patients to the
      development of major chronic metabolic diseases including type 2 diabetes
      mellitus. Adipose tissue expansion in obesity is characterized by increasing
      infiltration of proinflammatory immune cells into adipose tissue causing chronic,
      low-grade inflammation. Phenotypic switching of macrophages is an important
      mechanism of adipose tissue inflammation, and there is involvement of cells from
      the adaptive immune system in this process. T-cell phenotype changes and
      recruitment of B cells and T cells precedes macrophage infiltration. Cytokines
      and chemokines produced by immune cells influence localized and systemic
      inflammation, which is a pathogenic link between obesity and insulin resistance.
      Antigens absorbed from the gut might contribute to T-cell activation and
      recruitment into visceral adipose tissue in obesity. This Review summarizes, in
      the context of obesity, the evidence for infiltration of adipose tissue by cells
      of the adaptive immune system, how adaptive system cells affect innate cell
      populations and the influence of adaptive immune cells on the development of
      insulin resistance.

PMID- 22847241
TI  - Metabolism: LRH-1 is a transcriptional regulator of glucokinase in the liver.

PMID- 22847242
TI  - Reproductive endocrinology: Male fertility influenced by FSHB and FSHR
      polymorphisms?

PMID- 22847243
TI  - Reproductive endocrinology: Endothelial dysfunction in women with polycystic
      ovary syndrome--an inherent effect?

PMID- 22847244
TI  - Kinetic Monte Carlo modeling of silicate oligomerization and early gelation.
AB  - We present a lattice-gas kinetic Monte Carlo model to investigate the formation
      of silicate oligomers, their aggregation and the subsequent gelation process. In
      the early oligomerization stage, the 3-rings are metastable, 5-rings and 6-rings
      are formed in very small quantities, 4-rings are abundant species, linear and
      branched species are transformed into more compact structures. Results reveal
      that the gelation proceeds from 4-ring containing species. A significant amount
      of 5-rings and 6-rings, sharing Si with 4-ring, form in the aging stage. These
      reveal the formation mechanism of silicate rings and clusters during zeolite
      synthesis.

PMID- 22847245
TI  - Discontinuation of anti-TNF-alpha therapy in a Chinese cohort of patients with
      rheumatoid arthritis.
AB  - The aim of this retrospective study was to examine the predictors of
      discontinuation of anti-tumor necrosis factor (TNF) therapy due to adverse events
      in Chinese patients with rheumatoid arthritis (RA). Anti-TNF-related adverse
      events were recorded and analyzed in 217 consecutive patients with RA followed in
      our institution from 2003 to 2010. Time to discontinuation of anti-TNF-alpha
      therapy was estimated using survival analysis techniques. The anti-TNF agents
      administered were etanercept in 181 patients and adalimumab in 36 patients. The
      mean age at diagnosis was 45.2 +/- 13.5 years, and mean age at initiation of anti
      TNF therapy was 51.8 +/- 13.0 years. The mean duration of anti-TNF agent use was
      36.0 +/- 26.5 months (range, 1.4-87.0; median, 26.4 months). Of the 217 patients,
      39 (18.0 %) developed adverse events [etanercept in 34 (18.8 %] and adalimumab in
      5 (13.9 %)] during the treatment period (tuberculosis in 5, bacterial infections
      in 19, virus infection in 7, neuropathy in 3, malignancy in 3, other drug-related
      events in 1, and appendicitis in 1). In patients with RA, older age (>=55 years)
      at initiation of anti-TNF therapy [odds ratio (OR), 3.20; 95 % confidence
      interval (CI), 1.67-6.20; p < 0.001], Cr >=1.5 mg/dL (OR, 5.72; 95 % CI, 1.17
      27.90; p = 0.031), and occurrence of adverse events (OR, 3.82; 95 % CI, 1.75
      8.35; p = 0.001) were associated with increased likelihood of discontinuation of
      anti-TNF treatment. In the present study, a significant proportion (7.8 %,
      17/217) of patients with RA discontinued anti-TNF treatment because of adverse
      events. In the elderly and in patients with renal insufficiency, caution is
      needed when starting anti-TNF treatment.

PMID- 22847246
TI  - Improved single-limb balance after total knee arthroplasty.
AB  - PURPOSE: Unsteady ambulation shortly after total knee arthroplasty (TKA) may
      cause falling. Postural sway may predict the risk of falling. This prospective
      single-blinded observational study therefore evaluated the effects of TKA on
      single-limb standing balance (SLSB) and factors related to change in SLSB.
      METHODS: Patients with varus deformity and medial compartment degeneration were
      evaluated between September and December 2010. The Western Ontario and McMaster
      Universities Osteoarthritis Index and Kellgren/Lawrence scale were assessed, as
      were varus angle, number of painful knees, isometric peak torque of the
      quadriceps femoris, balance index of double limbs, and postural sway of single
      limbs. RESULTS: Twelve patients were enrolled and 11 were analysed. The mean +/-
      SD postural sway of single limbs (i.e., SLSB) was reduced significantly after
      TKA, from 30.3 +/- 20.8 cm to 18.5 +/- 9.3 cm (p = 0.02). Amelioration was in
      proportion to pre-operative postural sway (beta = 0.92). CONCLUSIONS: SLSB in
      patients with varus knees with osteoarthritis was improved significantly 11 days
      after TKA. Poorer pre-operative SLSB was associated with better post-operative
      SLSB. TKA may be useful for the immediate reduction of falling in patients with
      osteoarthritis.

PMID- 22847247
TI  - Cross cultural adaptation of the Achilles tendon Total Rupture Score with
      reliability, validity and responsiveness evaluation.
AB  - PURPOSE: The Achilles tendon Total Rupture Score (ATRS) was developed because of
      the need for a reliable, valid and sensitive instrument to evaluate symptoms and
      their effects on physical activity in patients following either conservative or
      surgical management of an Achilles tendon rupture. Prior to using the score in
      larger randomized trial in an English-speaking population, we decided to perform
      reliability, validity and responsiveness evaluations of the English version of
      the ATRS. Even though the score was published in English, the actual English
      version has not be validated and compared to the results of the Swedish version.
      METHODS: From 2009 to 2010, all patients who received treatment for Achilles
      tendon rupture were followed up using the English version of the ATRS. Patients
      were asked to complete the score at 3, 6 and 12 months following treatment for
      Achilles tendon rupture. The ATRS was completed on arrival in the outpatient
      clinic and again following consultation. RESULTS: The outcomes of 49 (13 female
      and 36 male) patients were assessed. The mean (SD) age was 49 (12) years, and 27
      patients had treatment for a left-sided rupture, 22 the right. All patients
      received treatment for ruptured Achilles tendons: 38 acute percutaneous repair, 1
      open repair, 5 an Achilles tendon reconstruction using a Peroneus Brevis tendon
      transfer for delayed presentation, 1 gracilis augmented repair for re-rupture and
      4 non-operative treatment for mid-portion rupture. The English version of ATRS
      was shown to have overall excellent reliability (ICC = 0.986). There was no
      significant difference between the results with the English version and the
      Swedish version when compared at the 6-month- or 12-month (n.s.) follow-up
      appointments. The effect size was 0.93. The minimal detectable change was 6.75
      points. CONCLUSIONS: The ATRS was culturally adapted to English and shown to be a
      reliable, valid and responsive method of testing functional outcome following an
      Achilles tendon rupture.

PMID- 22847248
TI  - Prospective study on retinal nerve fibre layer changes after an acute episode of
      phacomorphic angle closure.
AB  - To investigate the retinal nerve fibre layer (RNFL) changes after an acute attack
      of phacomorphic angle closure. This prospective study involved ten cases of
      phacomorphic angle closure that underwent cataract extraction and intraocular
      lens insertion after intraocular pressure lowering. Apart from visual acuity and
      intraocular pressure (IOP), RNFL thickness and vertical cup disc ratio (VCDR)
      were measured by optical coherence tomography (OCT) at 3-9 months post attack.
      Humphrey visual field assessment was performed at 9 months post attack. All cases
      had mean phacomorphic duration of <5 days. Postoperatively, best correct Snellen
      visual acuity was 0.4 +/- 0.2 and IOP at 9 months was 11.0 +/- 3.1 mmHg. There
      was no difference in VCDR and RNFL between the attack and contralateral eye at 3
      months post attack (both p = 0.4). At 9 months post attack, there was significant
      thinning in the average (p = 0.01), superior (p = 0.01), and inferior (p = 0.006)
      RNFL. There was no significant difference in the pattern standard deviation (PSD)
      between the two eyes on the Humphrey visual field nor was there any correlation
      between PSD severity and RNFL thinning (all p > 0.2. Patients with <5 days
      duration of phacomorphic angle closure are likely to have reasonable
      postoperative vision. An acute episode of phacomorphic angle closure can trigger
      an accelerated RNFL thinning despite normal IOP and open angles, most noticeable
      in the superior and inferior quadrants, occurring between 3 and 9 months post
      attack. Glaucomatous optic neuropathy in the attack eye was evident by OCT but
      not by visual field assessment at the same time interval.

PMID- 22847249
TI  - Clinical outcomes of non-Descemet stripping automated endothelial keratoplasty.
AB  - To describe the results of non-Descemet stripping automated endothelial
      keratoplasty (non-DSAEK). Retrospective, interventional, consecutive clinical
      case series. Twenty-three patients underwent non-DSAEK from January 2010 to
      February 2011. The various indications were pseudophakic corneal edema, aphakic
      corneal edema, failed graft, iridocorneal endothelial syndrome and congenital
      glaucoma. Corneal edema cleared in all patients within 1-4 weeks. Mean follow-up
      duration was 7.6 months. Post-operative best corrected visual acuity ranged from
      20/400 to 20/40. Fourteen patients had co-morbid factors affecting the vision. No
      patient had interface haze. Immediate post-operative complications were partial
      graft detachment (1 patient) and secondary angle closure (1 patient). Corneal
      clarity was restored following secondary interventions. One late post-operative
      complication was graft rejection at 6 months, leading to graft failure. Non-DSAEK
      is a safe and viable option in cases of corneal decompensation when the Descemet
      membrane is non-pathological.

PMID- 22847250
TI  - Effect of pH, mucin and bovine serum on rifampicin permeability through Caco-2
      cells.
AB  - Rifampicin, a poorly soluble drug, has great importance in therapeutics as it is
      the main drug used to treat tuberculosis. The characterization of its
      permeability and the factors that influence it represent an important tool for
      predicting its bioavailability. Caco-2 cell monolayers were used as models of the
      intestinal mucosa to assess the uptake and transport of rifampicin and the
      effects of various experimental conditions were investigated, in order to
      establish the influence of these variables on rifampicin permeability. Different
      pHs (5.8, 6.8 and 7.4) in the apical medium, the presence or absence of mucin
      (3.0% w/v) in the donor site and the presence or absence of bovine serum albumin
      (4.0% v/v) in the receptor chamber were the evaluated conditions. The
      quantification of rifampicin in the apical or basolateral chambers was performed
      by a validated HPLC-UV method. The change in the donor chamber pH showed that
      permeability values were greater at pH 6.8, although this increase does not
      result in an alteration of the qualitative classification of rifampicin, which
      has high permeability. Mucin and bovine serum showed no effects on the
      permeability of rifampicin at the concentration tested. Overall, the current
      study suggests that pH, artificial mucin and bovine serum proteins have no
      influence on rifampicin permeability.

PMID- 22847251
TI  - The limiting behaviour of a stochastic patch occupancy model.
AB  - Metapopulation models have been used to better understand the conditions
      necessary for the persistence of the metapopulation. In this paper, we study a
      stochastic patch occupancy model that incorporates variation in quality and
      connectivity of the habitat patches. Two important assumptions are imposed in our
      analysis. Firstly, the distance between patches has a special form. This amounts
      to assuming that migrating individuals follow certain pathways. Secondly, the
      area of the habitat patches is assumed to scale with the number of patches in the
      metapopulation. Under these assumptions, a deterministic limit is obtained as the
      number of patches goes to infinity. Using the deterministic limiting process, a
      condition for persistence of the metapopulation is derived.

PMID- 22847252
TI  - Improvement of sitting ability and ambulation status after selective peripheral
      neurotomy of the sciatic hamstring nerve together with obturator branches for
      severe spasticity of the lower extremities.
AB  - BACKGROUND: The authors used selective peripheral neurotomy (SPN) on the sciatic
      and obturator nerves to restore the sitting posture and ambulation in bedridden
      patients suffering from severe proximal lower limb spasticity. OBJECTIVE: To
      study the surgical outcome of sciatic and obturator neurotomies. METHODS: All
      patients with refractory hamstring spasticity who encountered SPN on the
      hamstring nerve were recruited. Obturator neurotomy was undertaken in some
      individuals. The clinical assessment included modified Ashworth scale (MAS),
      passive range of motion (PROM), sitting competency and ambulatory condition.
      These parameters were compared between before and after the surgery by using the
      Wilcoxon signed-rank test. RESULTS: Among the sciatic neurotomy group (n = 15),
      the mean pre- and postoperative MAS and PROM were 3.3 and 0.8 (p < 0.01) and 78.3
      and 121.7 degrees  (p < 0.01), respectively. Those measurements of the obturator
      nerve surgery group (n = 11) were 3.7 and 1.1 (p < 0.01) as well as 21.0 and 45.0
      degrees  (p < 0.01), respectively. Seven and 8 of a total of 9 patients had
      statistically significant improvement in sitting ability (p = 0.016) and
      ambulation status (p < 0.01), respectively. CONCLUSION: Bedridden patients who
      suffer from severe proximal lower limb spasticity have an optimum to return to
      sitting and ambulate with a wheelchair after SPN of the sciatic and obturator
      nerves.

PMID- 22847253
TI  - Alternative approaches for medical countermeasures to biological and chemical
      terrorism and warfare.
AB  - The desire to develop and evaluate drugs as potential countermeasures for
      biological and chemical threats requires test systems that can also substitute
      for the clinical trials normally crucial for drug development. Animal models have
      limited predictivity for drug efficacy, as is well known from many
      disappointments in clinical trials. Traditional in vitro and in silico approaches
      are not really game changers here, but the substantial investment into novel
      tools now underway might bring about a second generation of alternative
      approaches. The avenue pursued focuses primarily on the development of a Human on
      a Chip, i.e., the combination of different three-dimensional (stem) cell-based
      organ equivalents combined with microfluidics. The prospects of such approaches,
      their impact on the field of alternative approaches, and necessary complementary
      activities are discussed. The need to adapt quality assurance measures and
      experiences from validation is stressed.

PMID- 22847254
TI  - Characterization of mouse cell line IMA 2.1 as a potential model system to study
      astrocyte functions.
AB  - Astrocytes are activated in most chronic neurodegenerative diseases associated
      with inflammatory events such as Parkinson's disease or Alzheimer's disease, but
      also in stroke. Due to an aging population worldwide, research efforts in these
      areas are likely to expand in the future. This will entail an increased demand
      for appropriate experimental models. We introduce here the new immortalized mouse
      astrocyte cell line IMA 2.1 as an alternative to currently used primary astrocyte
      cultures. IMA 2.1 were directly compared with primary mouse astrocytes with
      respect to their response to proinflammatory stimuli, expression of typical
      astrocyte markers, and to the cell line's capacity to metabolize the parkinsonian
      toxin MPTP to its toxic metabolite MPP+. Under inflammatory conditions, mimicked
      with the addition of a cytokine mix, IMA 2.1 responded similarly to primary
      astrocytes with mRNA upregulation, expression of iNOS and COX-2, and the release
      of various inflammatory mediators. Analysis of astrocytic markers indicated that
      IMA 2.1 represent a relatively early, GFAP-negative stage of astrocyte
      development. Moreover, conversion of MPTP by monoamine oxidase-B proceeded in IMA
      at least as quickly as in primary cells. For all endpoints investigated, the cell
      line IMA 2.1, derived from a single clone, delivered reproducible results over a
      period of several years and allowed upscaling of experiments due to its easy
      handling compared with primary cells.

PMID- 22847256
TI  - Regulatory acceptance and use of 3R models: a multilevel perspective.
AB  - The importance placed on risk avoidance in our society has resulted in a broad
      range of regulations intended to guarantee safety of products such as
      pharmaceuticals and chemicals. Many of these regulations rely on animal tests. As
      a result, about 25% of the animal experiments in Europe are done for regulatory
      purposes. There are many initiatives that aim to replace, reduce, or refine
      laboratory animal use, but the regulatory acceptance and use of 3R models lags
      behind. The central question of this study is: "Which variables influence the
      regulatory acceptance and use of 3R models and in what way?" Regulatory
      acceptance is seen as one of the biggest hurdles 3R models face, but the
      rationale behind this is still underexplored. This study is an approach to
      filling that gap by combining opinions from experts in the field with literature
      on technology acceptance and risk regulation, resulting in a model of the
      variables that determine the process of the regulatory acceptance and use of 3R
      models.

PMID- 22847255
TI  - Screening of budesonide nanoformulations for treatment of inflammatory bowel
      disease in an inflamed 3D cell-culture model.
AB  - Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are
      mostly conducted in chemically induced rodent models that represent acute injury
      caused inflammation instead of a chronic condition. To accurately screen drug
      formulations for chronic IBD, a relevant model that mimics the chronic condition
      in vitro is urgently needed. In an effort to reduce and potentially replace this
      scientifically and ethically questionable animal testing for IBD drugs, our
      laboratory has developed an in vitro model for the inflamed intestinal mucosa
      observed in chronic IBD, which allows high-throughput screening of anti
      inflammatory drugs and their formulations. The in vitro model consists of
      intestinal epithelial cells, human blood-derived macrophages, and dendritic cells
      that are stimulated by the inflammatory cytokine interleukin-1beta. In this
      study, the model was utilized for evaluation of the efficacy and deposition of
      budesonide, an anti-inflammatory drug, in three different pharmaceutical
      formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles,
      and (3) encapsulated into liposomes. The in vitro model of the inflamed
      intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy
      among the formulations while maintaining the convenience of conventional in vitro
      studies and adequately representing the complex pathophysiological changes
      observed in vivo.

PMID- 22847257
TI  - Inconsistencies in data requirements of EU legislation involving tests on
      animals.
AB  - European Union (EU) legislation on the protection of animals used for scientific
      purposes requires that alternative methods must be used instead of animal tests
      wherever they are available. Unfortunately, this provision is not implemented to
      its full extent when it comes to risk assessment of chemicals and new products
      prior to their authorization and placing on the market in the EU. In this study,
      we screened data requirements of relevant EU law regarding chemicals (REACH),
      biocides, pesticides, and food safety (Novel Food) and found that data
      requirements as part of the risk assessment do not always reflect state-of-the
      art science and technology. Most of the data requirements we investigated still
      include testing on animals for many toxicological endpoints, even though more
      than 40 alternative testing methods accepted at the level of the EU or the OECD
      are available. This may be due to a multitude of reasons, including a shortage of
      both manpower to implement existing knowledge and expertise in the field of
      alternative methods, as well as unclear and misleading statements on the
      applicability and state of validation of alternative methods. In conclusion, we
      strongly suggest a homogeneous EU-wide approach for all areas involving risk
      assessment of substances with the goal of better implementing the 3Rs and
      complying with Directive 2010/63/EU. This also would streamline data
      requirements, save costs on various levels, and enhance product safety for
      consumers.

PMID- 22847258
TI  - A modulating effect of epigallocatechin gallate (EGCG), a tea catechin, on the
      bladder of rats exposed to water avoidance stress.
AB  - AIMS: To examine the effect of epigallocatechin gallate (EGCG), a green tea
      catechin, on the bladder of rats exposed to water avoidance stress (WAS).
      METHODS: Twenty female Sprague-Dawley rats were divided into four groups of five.
      The first group was exposed to WAS for7 days. The second group was pretreated
      with EGCG 1 mg/kg intraperitoneally (IP) for 7 days before exposure to WAS. The
      treatment was continued till the end of the experiment. The third group was
      placed on the platform in a container without water for 2 hr daily for 7 days
      (Sham WAS). The fourth group was pretreated with saline I.P. for 7 days before
      being exposed to sham WAS. PRIMARY OUTCOME: Bladder wall evaluation for signs of
      inflammation and total and activated mast cell counts. Secondary outcome: fecal
      pellet output and micturition frequency at baseline, day 1 and day 7. RESULTS:
      Bladder walls from rats exposed to WAS revealed significantly higher inflammation
      score, total and degranulated mast cell counts compared to the sham WAS group.
      EGCG administration had an obvious protective effect on the bladder mucosa, as
      the inflammation score, total and degranulated mast cell counts were all
      significantly lower than in the WAS group. In the WAS group, fecal pellet output
      and micturition frequency increased above baseline throughout the experiment.
      Comparison of sham WAS group versus sham WAS with saline revealed no
      statistically significant difference in any parameter. CONCLUSIONS: EGCG given at
      1 mg/kg I.P to rats has a significant protective effect against bladder
      degenerative changes following WAS.

PMID- 22847260
TI  - Effect of a rock dust amendment on disease severity of tomato bacterial wilt.
AB  - Nutrients are important for growth and development of plants and microbes, and
      they are also important factors in plant disease control. The objective of this
      study was to evaluate the effect of a rock dust used as a fertilizer in
      maintaining health of soil and tomato plants under greenhouse conditions. Four
      treatments-including M (commercial organic fertilizer), A (rock dust soil
      amendment), M + A (commercial organic fertilizer + rock dust soil amendment) and
      CK (blank control)--were examined for their effect on soil properties, soil
      enzymatic activity, plant growth and control efficacy against tomato bacterial
      wilt. Treatments A and M + A were significantly better than other treatments in
      changing soil pH, increasing it from acidic (pH 5.13) to nearly neutral (pH 6.81
      and 6.70, respectively). Enzymatic activities in soil were notably influenced by
      the different treatments--particularly treatment M + A, which increased the
      activities of alkaline phosphatase, urease, catalase and sucrase to a greater
      extent in soil. There was no significant difference (P < 0.05) in the effects of
      treatments A and M + A on tomato plant height, stem diameter and biomass. The
      effect of the four treatments on the chlorophyll content and photosynthetic rate
      (in decreasing order) were M + A, A, M and CK. The replicate greenhouse
      experiments showed that the control efficacies of treatments M + A, A, and M
      against bacterial wilt were respectively 89.99, 81.11 and 8.89 % in first
      experiment and with the efficacies of 84.55, 74.36, and 13.49 % in the replicate;
      indicating that rock dust played a key role in the plant-soil interaction. The
      raised soil pH and Ca content were the key factors for the rock dust amendment
      controlling bacterial wilt under greenhouse conditions.

PMID- 22847261
TI  - Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use
      for enhancing erythromycin production.
AB  - Genome-scale metabolic reconstructions are routinely used for the analysis and
      design of metabolic engineering strategies for production of primary metabolites.
      The use of such reconstructions for metabolic engineering of antibiotic
      production is not common due to the lack of simple design algorithms in the
      absence of a cellular growth objective function. Here, we present the metabolic
      network reconstruction for the erythromycin producer Saccharopolyspora erythraea
      NRRL23338. The model was manually curated for primary and secondary metabolism
      pathways and consists of 1,482 reactions (2,075 genes) and 1,646 metabolites. As
      part of the model validation, we explored the potential benefits of supplying
      amino acids and identified five amino acids "compatible" with erythromycin
      production, whereby if glucose is supplemented with this amino acid on a carbon
      mole basis, the in silico model predicts that high erythromycin yield is possible
      without lowering biomass yield. Increased erythromycin titre was confirmed for
      four of the five amino acids, namely valine, isoleucine, threonine and proline.
      In bioreactor experiments, supplementation with 2.5 % carbon mole of valine
      increased the growth rate by 20 % and simultaneously the erythromycin yield on
      biomass by 50 %. The model presented here can be used as a framework for the
      future integration of high-throughput biological data sets in S. erythraea and
      ultimately to realise strain designs capable of increasing erythromycin
      production closer to the theoretical yield.

PMID- 22847262
TI  - Cytochrome P450 1A1 Ile462Val polymorphism and oral carcinoma risk: an updated
      meta-analysis including 1,515 cases and 2,233 controls.
AB  - Cytochrome P450 (CYP) 1A1 Ile462Val (exon7) polymorphism has been suggested to be
      a risk factor for several cancers. Published data on its association with oral
      cancer risk have generated conflicting results. Our previous meta-analysis
      containing data from prior to Jan 2008 regarding this issue failed to find a
      significant association between CYP1A1 Ile462Val variation and oral cancer
      susceptibility. An updated meta-analysis with eligible studies for the period up
      to May 2012 was conducted. Separate analyses on ethnicity and source of controls
      were also performed. A total of 13 case-control studies comprising 1,515 cases
      and 2,233 controls were lastly selected for analysis. Compared with the previous
      meta-analysis, the overall data also failed to indicate a significant association
      of CYP1A1 Ile462Val polymorphism with oral cancer risk (Val/Val vs. Ile/Ile--OR =
      1.46; 95 % CI = 0.96-2.24; dominant model--OR = 1.01; 95 % CI = 0.81-1.25; and
      recessive model--OR = 1.46; 95 % CI = 0.96-2.23). However, in the subgroup
      analysis by ethnicity, increased cancer risk was observed among Asians under the
      additive and recessive models (Val/Val vs. Ile/Ile--OR = 1.74; 95 % CI = 1.04
      2.90 and recessive model-OR = 1.73; 95 % CI = 1.04-2.87), inconsistent with the
      previous meta-analysis. Collectively, the data of the present study suggest that
      CYP1A1 variant Val/Val alleles might modify the susceptibility to oral cancer
      among Asians. Further well-designed investigations with large sample sizes are
      required to confirm this conclusion.

PMID- 22847263
TI  - Elevated methylation of HPV16 DNA is associated with the development of high
      grade cervical intraepithelial neoplasia.
AB  - We explored the association of human papillomavirus type 16 (HPV16) DNA
      methylation with age, viral load, viral persistence and risk of incident and
      prevalent high grade CIN (CIN2+) in serially collected specimens from the
      Guanacaste, Costa Rica cohort. 273 exfoliated cervical cell specimens (diagnostic
      and pre-diagnostic) were selected: (1) 92 with HPV16 DNA clearance (controls),
      (2) 72 with HPV16 DNA persistence (without CIN2+) and (3) 109 with CIN2+. DNA was
      extracted, bisulfite converted and methylation was quantified using
      pyrosequencing assays at 66 CpGs across the HPV genome. The Kruskal-Wallis test
      was used to determine significant differences among groups, and receiver
      operating characteristic curve analyses were used to evaluate how well
      methylation identified women with CIN2+. In diagnostic specimens, 88% of CpG
      sites had significantly higher methylation levels in CIN2+ after correction for
      multiple tests compared with controls. The highest area under the ROC curve (AUC)
      was 0.82 for CpG site 6457 in L1, and a diagnostic sensitivity of 91%
      corresponded to a specificity of 60% for CIN2+. Prospectively, 17% of CpG sites
      had significantly higher methylation in pre-diagnostic CIN2+ specimens (median
      time of 3 years before diagnosis) versus controls. The strongest pre-diagnostic
      CpG site was 6367 in L1 with an AUC of 0.76. Age-stratified analyses suggested
      that women older than the median age of 28 years have an increased risk of
      precancer associated with high methylation. Higher methylation in CIN2+ cases was
      not explained by higher viral load. We conclude that elevated levels of HPV16 DNA
      methylation may be useful to predict concurrently diagnosed as well as future
      CIN2+.

PMID- 22847266
TI  - Infection systems biology: from reactive to proactive (P4) medicine.
AB  - This short review establishes the conceptual bases and discusses the principal
      aspects of P4-shorthand for predictive, preventive, personalized and
      participatory medicine-medicine, in the framework of infectious diseases. P4
      medicine is a new way to approach medical care; instead of acting when the
      patient is sick, physicians will be able to detect early warnings of disease to
      take early action. Furthermore, people might even be able to adjust their
      lifestyles to prevent disease. P4 medicine is fuelled by systems approaches to
      disease, including methods for personalized genome sequencing and new
      computational techniques for building dynamic disease predictive networks from
      massive amounts of data from a variety of OMICs. An excellent example of the
      effectiveness of the P4 medicine approach is the change in cancer treatments.
      Emphasis is placed on early detection, followed by genotyping of the patient to
      use the most adequate treatment according to the genetic background.
      Cardiovascular diseases and perhaps even neurodegenerative disorders will be the
      next targets for P4 medicine. The application of P4 medicine to infectious
      diseases is still in its infancy, but is a promising field that will provide much
      benefit to both the patients and the health-care system.

PMID- 22847264
TI  - Characterization of cellular protective effects of ATP13A2/PARK9 expression and
      alterations resulting from pathogenic mutants.
AB  - Mutations in ATP13A2, which encodes a lysosomal P-type ATPase of unknown
      function, cause an autosomal recessive parkinsonian syndrome. With mammalian
      cells, we show that ATP13A2 expression protects against manganese and nickel
      toxicity, in addition to proteasomal, mitochondrial, and oxidative stress.
      Consistent with a recessive mode of inheritance of gene defects, disease-causing
      mutations F182L and G504R are prone to misfolding and do not protect against
      manganese and nickel toxicity because they are unstable as a result of
      degradation via the endoplasmic reticulum-associated degradation (ERAD)
      proteasome system. The protective effects of ATP13A2 expression are not due to
      inhibition of apoptotic pathways or a reduction in typical stress pathways,
      insofar as these pathways are still activated in challenged ATP13A2-expressing
      cells; however, these cells display a dramatic reduction in the accumulation of
      oxidized and damaged proteins. These data indicate that, contrary to a previous
      suggestion, ATP13A2 is unlikely to convey cellular resilience simply by acting as
      a lysosomal manganese transporter. Consistent with the recent identification of
      an ATP13A2 recessive mutation in Tibetan terriers that develop neurodegeneration
      with neuronal ceroid lipofucinoses, our data suggest that ATP13A2 may function to
      import a cofactor required for the function of a lysosome enzyme(s).

PMID- 22847267
TI  - Unique biological properties of Mycobacterium tuberculosis L-form variants:
      impact for survival under stress.
AB  - Bacteria can, under certain conditions, enter into a cell-less state known as L
      form conversion. This phenomenon is universal, but also recognized with
      difficultly by microbiologists. The current study addresses several aspects
      concerning the ability of tubercle bacilli to use L-form conversion as a unique
      adaptive strategy to survive and reproduce under unfavorable conditions. Nutrient
      starvation of M. tuberculosis in vitro followed by passages in Middlebrook 7H9
      semisolid medium was used for stress induction and the selective isolation of
      mycobacterial L-form variants. Light and electron microscopy images evidence the
      peculiar characteristics of mycobacterial L-forms. For example, mycobacterial L
      forms were observed to lose their acid-fastness and change their morphology. In
      addition, wide morphological variability, the presence of large and elementary
      bodies, coccoids and small granular forms, as well as the appearance of unusual
      modes of irregular cell division were observed. Unlike classical tubercle
      bacilli, L-form variants grew and developed typical "fried-egg" colonies faster.
      L-forms were verified as M. tuberculosis by spoligotyping. The results provide
      insights into the nature of L-form phenomena in M. tuberculosis and link them to
      the mechanisms allowing mycobacterial survival under stress.

PMID- 22847268
TI  - Essential role of the czc determinant for cadmium, cobalt and zinc resistance in
      Gluconacetobacter diazotrophicus PAl 5.
AB  - The mechanisms of cadmium, cobalt and zinc resistance were characterized in the
      plant-growth-promoting bacterium Gluconacetobacter diazotrophicus PAl 5. The
      resistance level of the wild-type strain was evaluated through the establishment
      of minimum inhibitory concentrations (MIC) of the soluble compounds CdCl2.H2O,
      CoCl2.6H2O and ZnCl2. Gluconacetobacter diazotrophicus PAl 5 was resistant to
      high concentrations of Cd, Co and Zn, with MICs of 1.2, 20 and 20 mM,
      respectively. Screening of an insertion library from transposon EZ-Tn5
      <R6Kyori/KAN-2> in the presence of ZnO revealed that the mutant GDP30H3 was
      unable to grow in the presence of the compound. This mutant was also highly
      sensitive to CdCl2.H2O, CoCl2.6H2O and ZnCl2. Molecular characterization
      established that the mutation affected the czcA gene, which encodes a protein
      involved in metal efflux. In silico analysis showed that czcA is a component of
      the czcCBARS operon together with four other genes. This work provides evidence
      of the high tolerance of G. diazotrophicus PAl 5 to heavy metals and that czc is
      a determinant for metal resistance in this bacterium.

PMID- 22847269
TI  - Identification of virulence markers in clinically relevant strains of
      Acinetobacter genospecies.
AB  - Nine Acinetobacter strains from patients and hospital environment were analyzed
      for virulence markers, quorum sensing signal production, and the presence of luxI
      and luxR genes. The strains had several properties in common: growth in iron
      limited condition, biofilm formation, and no active protease secretion.
      Significantly higher catechol production was determined in patient isolates (P <
      0.03), but other invasiveness markers, such as lipase secretion, amount of
      biofilm, cell motility, antibiotic resistance, and hemolysin production, showed
      large variability. Notably, all members of the so-called A. calcoaceticus-A.
      baumannii complex, regardless of whether the source was a patient or
      environmental, secreted mediumto long-chain N-acyl homoserine lactones (AHL) and
      showed blue light inhibition of cell motility. In these strains, a luxI homologue
      with a homoserine lactone synthase domain and a luxR putative regulator
      displaying the typical AHL binding domain were identified.

PMID- 22847271
TI  - Coarctate cyclization reactions: a primer.
AB  - The cleavage of five-membered heterocycles possessing an exocyclic carbene or
      nitrene to form conjugated ene-ene-yne systems has been documented for over 40
      years; however, the reverse reaction, using a conjugated "ene-ene-yne" precursor
      to form a heterocycle is a relatively new approach. Over the past decade, the
      Haley and Herges groups have studied computationally and experimentally the
      cyclization of the "hetero-ene-ene-yne" motif via an unusual class of concerted
      reactions known as coarctate reactions. This feature article details our
      synthetic and mechanistic work involving triazene-arene-alkynes and structurally
      related systems to generate heterocycles using coarctate chemistry.

PMID- 22847270
TI  - The role of plant type and salinity in the selection for the denitrifying
      community structure in the rhizosphere of wetland vegetation.
AB  - Coastal wetlands, as transient links from terrestrial to marine environments, are
      important for nitrogen removal by denitrification. Denitrification strongly
      depends on both the presence of emergent plants and the denitrifier communities
      selected by different plant species. In this study, the effects of vegetation and
      habitat heterogeneity on the community of denitrifying bacteria were investigated
      in nine coastal wetlands in two preserved areas of Spain. Sampling locations were
      selected to cover a range of salinity (0.81 to 31.3 mS/cm) and nitrate
      concentrations (0.1 to 303 MUM NO3-), allowing the evaluation of environmental
      variables that select for denitrifier communities in the rhizosphere of
      Phragmites sp., Ruppia sp., and Paspalum sp. Potential nitrate reduction rates
      were found to be dependent on the sampling time and plant species and related to
      the denitrifier community structure, which was assessed by terminal restriction
      fragment length polymorphism analysis of the functional genes nirS, nirK and
      nosZ. The results showed that denitrifier community structure was also governed
      by plant species and salinity, with significant influences of other variables,
      such as sampling time and location. Ruppia sp. and Phragmites sp. selected for
      certain communities, whereas this was not the case for Paspalum sp. The plant
      species effect was strongest on nirK-type denitrifiers, whereas water carbon
      content was a significant factor defining the structure of the nosZ-harboring
      community. The differences recognized using the three functional gene markers
      indicated that different drivers act on denitrifying populations capable of
      complete denitrification, compared to the overall denitrifier community. This
      finding may have implications for emissions of the greenhouse gas nitrous oxide.

PMID- 22847272
TI  - Development: triggering meiotic fate.

PMID- 22847275
TI  - Self-assembly of a catechol-based macrocycle at the liquid-solid interface:
      experiments and molecular dynamics simulations.
AB  - This combined experimental (STM, XPS) and molecular dynamics simulation study
      highlights the complex and subtle interplay of solvent effects and surface
      interactions on the 2-D self-assembly pattern of a Schiff-base macrocycle
      containing catechol moieties at the liquid-solid interface. STM imaging reveals a
      hexagonal ordering of the macrocycles at the n-tetradecane/Au(111) interface,
      compatible with a desorption of the lateral chains of the macrocycle.
      Interestingly, all the triangular-shaped macrocycles are oriented in the same
      direction, avoiding a close-packed structure. XPS experiments indicate the
      presence of a strong macrocycle-surface interaction. Also, MD simulations reveal
      substantial solvent effects. In particular, we find that co-adsorption of solvent
      molecules with the macrocycles induces desorption of lateral chains, and the
      solvent molecules act as spacers stabilizing the open self-assembly pattern.

PMID- 22847274
TI  - Isolation, preliminary characterization, and full-genome analyses of tick-borne
      encephalitis virus from Mongolia.
AB  - Tick-borne encephalitis virus (TBEV) causes one of the most important
      inflammatory diseases of the central nervous system, namely severe encephalitis
      in Europe and Asia. Since the 1980s tick-borne encephalitis is known in Mongolia
      with increasing numbers of human cases reported during the last years. So far,
      however, data on TBEV strains are still sparse. We herein report the isolation of
      a TBEV strain from Ixodes persulcatus ticks collected in Mongolia in 2010.
      Phylogenetic analysis of the E-gene classified this isolate as Siberian subtype
      of TBEV. The Mongolian TBEV strain showed differences in virus titers, plaque
      sizes, and growth properties in two human neuronal cell-lines. In addition, the
      10,242 nucleotide long open-reading frame and the corresponding polyprotein
      sequence were revealed. The isolate grouped in the genetic subclade of the
      Siberian subtype. The strain Zausaev (AF527415) and Vasilchenko (AF069066) had 97
      and 94 % identity on the nucleotide level. In summary, we herein describe first
      detailed data regarding TBEV from Mongolia. Further investigations of TBEV in
      Mongolia and adjacent areas are needed to understand the intricate dispersal of
      this virus.

PMID- 22847276
TI  - My mentors.

PMID- 22847273
TI  - The continuing value of twin studies in the omics era.
AB  - The classical twin study has been a powerful heuristic in biomedical, psychiatric
      and behavioural research for decades. Twin registries worldwide have collected
      biological material and longitudinal phenotypic data on tens of thousands of
      twins, providing a valuable resource for studying complex phenotypes and their
      underlying biology. In this Review, we consider the continuing value of twin
      studies in the current era of molecular genetic studies. We conclude that
      classical twin methods combined with novel technologies represent a powerful
      approach towards identifying and understanding the molecular pathways that
      underlie complex traits.

PMID- 22847277
TI  - A murine closed-chest model of myocardial ischemia and reperfusion.
AB  - Surgical trauma by thoracotomy in open-chest models of coronary ligation induces
      an immune response which modifies different mechanisms involved in ischemia and
      reperfusion. Immune response includes cytokine expression and release or
      secretion of endogenous ligands of innate immune receptors. Activation of innate
      immunity can potentially modulate infarct size. We have modified an existing
      murine closed-chest model using hanging weights which could be useful for
      studying myocardial pre- and postconditioning and the role of innate immunity in
      myocardial ischemia and reperfusion. This model allows animals to recover from
      surgical trauma before onset of myocardial ischemia. Volatile anesthetics have
      been intensely studied and their preconditioning effect for the ischemic heart is
      well known. However, this protective effect precludes its use in open chest
      models of coronary artery ligation. Thus, another advantage could be the use of
      the well controllable volatile anesthetics for instrumentation in a chronic
      closed-chest model, since their preconditioning effect lasts up to 72 hours.
      Chronic heart diseases with intermittent ischemia and multiple hit models are
      other possible applications of this model. For the chronic closed-chest model,
      intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th
      intercostal space. Following identification of the left anterior descending a
      ligature is passed underneath the vessel and both suture ends are threaded
      through an occluder. Then, both suture ends are passed through the chest wall,
      knotted to form a loop and left in the subcutaneous tissue. After chest closure
      and recovery for 5 days, mice are anesthetized again, chest skin is reopened and
      hanging weights are hooked up to the loop under ECG control. At the end of the
      ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size
      assessment or undergo perfusion fixation to allow morphometric studies in
      addition to histology and immunohistochemistry.

PMID- 22847278
TI  - Detection of cross infections by Leishmania spp. and Trypanosoma spp. in dogs
      using indirect immunoenzyme assay, indirect fluorescent antibody test and
      polymerase chain reaction.
AB  - The aim of this study was to detect cross infections by Leishmania spp. and
      Trypanosoma spp. using enzyme-linked immunosorbent assay (ELISA), indirect
      fluorescent antibody test (IFAT) and polymerase chain reaction (PCR). Thus, 408
      blood samples were collected from dogs domiciled in Aracatuba Municipality, Sao
      Paulo State, Brazil; the dogs were of both sexes, of several breeds and aged 6
      months. For Leishmania spp., 14.95% (61 out of 408) of dogs were reactive using
      IFAT. Positivity was 20.10% (82 out of 408) using ELISA and 29.66% (121 out of
      408) using PCR, with significant differences for the sex and age of these animals
      (p < 0.05). For Trypanosoma spp., antibody occurrence using ELISA was 10.54% (43
      out of 408), while PCR indicated 2.45% (10 out of 408) positive dogs. Using IFAT,
      10.29% (42 out of 408) of animals were considered positive and only sex showed a
      significant difference (p < 0.05). In this study, 10.54% (43 out of 408) of
      animals were seropositive according to ELISA for Trypanosoma spp., of which
      79.07% (34 out of 43) showed positive results in the molecular diagnosis for
      Leishmania spp., while of the 10.29% (42 out of 408) positive dogs according to
      IFAT, 95.24 % (40 out of 42) had confirmed infection by this parasite. The
      obtained results demonstrate evidence of cross infections by both protozoa in the
      animals analysed in this study.

PMID- 22847279
TI  - Activity of tea tree oil and nerolidol alone or in combination against Pediculus
      capitis (head lice) and its eggs.
AB  - Head lice infestation is an emerging social problem in undeveloped and developed
      countries. Because of louse resistance increasing, several long-used insecticidal
      compounds have lost their efficacy, and alternatives, such as essential oils,
      have been proposed to treat this parasitic infestation. The present study
      investigated the efficacy of two natural substances: tea tree (Melaleuca
      alternifolia) oil and nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol)
      against lice and its eggs. Products were used alone and in combination (ratio 1:1
      and 1:2) from 8 % dilution. The in vitro effect of natural substances at
      different concentrations were evaluated against 69 head lice (adults and nymphs)
      and 187 louse eggs collected from school children in Chieti-Pescara (Central
      Italy) over a 6-month period. The lice mortality was evaluated for 24 h by a
      stereo light microscope. The ovicidal activity was monitored by microscopic
      inspections for 15 days. Tea tree oil was more effective than nerolidol against
      head lice with 100 % mortality at 30 min and 1 % concentration. On the contrary,
      nerolidol expressed a more pronounced ovicidal activity inducing the failure of
      50 % of the eggs to hatch at 1 % concentration after 4 days; the same effect was
      achieved by using a twice concentration of tea tree oil. The association of the
      two substances both in ratios 1:1 and 1:2 combined efficaciously their
      insecticidal and ovicidal effect; in particular, the ratio 1:2 (tea tree oil 0.5
      % plus nerolidol 1 %) acted producing both the death of all head lice at 30 min
      and the abortive effect of louse eggs after 5 days. These results offer new
      potential application of natural compounds and display a promising scenario in
      the treatment of pediculosis resistant cases. The development of novel
      pediculicides containing essential oils could be, in fact, an important tool to
      control the parasitic infestation.

PMID- 22847280
TI  - Interdigitated array of Pt electrodes for electrical stimulation and engineering
      of aligned muscle tissue.
AB  - Engineered skeletal muscle tissues could be useful for applications in tissue
      engineering, drug screening, and bio-robotics. It is well-known that skeletal
      muscle cells are able to differentiate under electrical stimulation (ES), with an
      increase in myosin production, along with the formation of myofibers and
      contractile proteins. In this study, we describe the use of an interdigitated
      array of electrodes as a novel platform to electrically stimulate engineered
      muscle tissues. The resulting muscle myofibers were analyzed and quantified in
      terms of their myotube characteristics and gene expression. The engineered muscle
      tissues stimulated through the interdigitated array of electrodes demonstrated
      superior performance and maturation compared to the corresponding tissues
      stimulated through a conventional setup (i.e., through Pt wires in close
      proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage
      6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated
      array of electrodes resulted in a higher degree of C2C12 myotube alignment (~80%)
      as compared to ES using Pt wires (~65%). In addition, higher amounts of C2C12
      myotube coverage area, myotube length, muscle transcription factors and protein
      biomarkers were found for myotubes stimulated through the interdigitated array of
      electrodes compared to those stimulated using the Pt wires. Due to the wide array
      of potential applications of ES for two- and three-dimensional (2D and 3D)
      engineered tissues, the suggested platform could be employed for a variety of
      cell and tissue structures to more efficiently investigate their response to
      electrical fields.

PMID- 22847282
TI  - Election year:  a golden opportunity for nursing.

PMID- 22847283
TI  - Adolescents with celiac disease: a literature review of the impact developmental
      tasks have on adherence with a gluten-free diet.
AB  - Celiac disease is an autoimmune disease affecting individuals at any time across
      the developmental lifespan. The only treatment for celiac disease is lifelong
      adherence to a gluten-free diet to prevent future complications and malignancies.
      The ratio of occurrence between children and adolescents is 1:104. When the phase
      of adolescence is coalesced with having celiac disease, normal developmental
      tasks become more challenging, therefore impacting adherence with the gluten-free
      diet. An abundance of both qualitative and quantitative studies from the
      Netherlands, Europe, and Canada focusing on adolescents with celiac disease and
      adherence to the gluten-free diet was found in the literature. Conversely, in the
      United States, there was a dearth of literature examining adolescents diagnosed
      with celiac disease, their adherence to a gluten-free diet, and their lived
      experience of having celiac disease. The relevance to nursing practice and
      recommendations for future research are discussed in light of these findings.

PMID- 22847281
TI  - Embryonic stem cell interactomics: the beginning of a long road to biological
      function.
AB  - Embryonic stem cells (ESCs) are capable of unlimited self-renewal while
      maintaining pluripotency. They are of great interest in regenerative medicine due
      to their ability to differentiate into all cell types of the three embryonic germ
      layers. Recently, induced pluripotent stem cells (iPSCs) have shown similarities
      to ESCs and thus promise great therapeutic potential in regenerative medicine.
      Despite progress in stem cell biology, our understanding of the exact mechanisms
      by which pluripotency and self-renewal are established and maintained is largely
      unknown. A better understanding of these processes may lead to discovery of
      alternative ways for reprogramming, differentiation and more reliable
      applications of stem cells in therapies. It has become evident that proteins
      generally function as members of large complexes that are part of a more complex
      network. Therefore, the identification of protein-protein interactions (PPI) is
      an efficient strategy for understanding protein function and regulation.
      Systematic genome-wide and pathway-specific PPI analysis of ESCs has generated a
      network of ESC proteins, including major transcription factors. These PPI
      networks of ESCs may contribute to a mechanistic understanding of self-renewal
      and pluripotency. In this review we describe different experimental approaches
      for the identification of PPIs along with various databases. We discuss
      biological findings and technical challenges encountered with interactome studies
      of pluripotent stem cells, and provide insight into how interactomics is likely
      to develop.

PMID- 22847284
TI  - Electrocardiographic, cardiac enzymes, and magnesium in patients with severe
      acute pancreatitis.
AB  - Severe acute pancreatitis (SAP) can lead to multiple-organ dysfunction syndrome
      (MODS). Electrocardiographic (ECG), cardiac enzyme, and serum magnesium
      abnormalities occur after SAP. Electrocardiographic and cardiac enzyme
      abnormalities are described as variables in SAP patients, which contribute to the
      effects of MODS. Hypomagnesium is also closely associated with ECG abnormalities;
      therefore, hypomagnesium was also considered to be a variable in this study. A
      consecutive series of 54 patients admitted within 72 hours after SAP occurred was
      studied. A standard 12-lead ECG, cardiac enzyme, and serum magnesium measurement
      were routinely performed at admission. Linear correlation was used to analyze the
      relationship between hypomagnesemia and sinus tachycardia. The nonparametic
      binomial test was used to analyze dichotomized dependent variables (premature
      beat, atrial fibrillation, ST-segment depression, abnormal T wave, and long QT
      interval). Hypomagnesemia was present in 15 patients (28%), who subsequently had
      sinus tachycardia. There was a significant negative relationship (-1 < r <0)
      between hypomagnesemia and sinus tachycardia (p < .05). There were 14 (17%)
      premature beat, 7 (8%) atrial fibrillation, 21 (25%) ST-segment depression, 18
      (21%) abnormal T wave, and 17 (31%) long QT-interval events in 54 SAP patients.
      Hypomagnesemia is a reason for ECG abnormalities. Electrocardiographic and
      cardiac enzyme abnormalities are considered to be transitory variables that are
      present in patients with SAP.

PMID- 22847285
TI  - Nickel allergy: what it is and how it can affect our patient care.
AB  - Nickel allergy is the second most common form of allergic contact dermatitis skin
      allergy, second only to poison ivy. There is no cure for a nickel allergy. The
      best treatment is to avoid contact with all products known to have nickel
      content. Because nickel is present in a vast amount of items used every day in
      the gastroenterology endoscopy setting, it is not possible to have a nickel-free
      environment. Nurses need to be aware of items in their facility, which could
      affect the nickel-allergic patient in an adverse way. The focus should be to
      limit patient exposure as much as possible. This article provides an overview of
      nickel allergy and areas of risk for patients in the gastroenterology endoscopy
      setting.

PMID- 22847287
TI  - The effect of a sweet potato, footbath, and acupressure intervention in
      preventing constipation in hospitalized patients with acute coronary syndromes.
AB  - Constipation is a common health problem that adversely affects quality of life
      and the prognosis of hospitalized patients with acute coronary syndromes (ACS).
      The purpose of this study was to develop and test the sweet
      potato/footbath/acupressure massage (SFA) intervention as a safe treatment for
      prevention of constipation and to increase satisfaction with bowel emptying in
      hospitalized patients with ACS. The study was a prospective, randomized
      controlled trial with a sample of 93 patients (SFA group, n = 44; usual care
      group, n = 49). Patients in the SFA group received SFA intervention combined with
      usual care. The results showed that there were statistical differences between
      the two groups in terms of (1) the incidence of constipation; (2) the use of
      laxatives and enemas; (3) patients' subjective satisfaction with their bowel
      emptying during hospitalization; and (4) sensation of incomplete evacuation and
      anorectal obstruction/blockade. The SFA intervention was more effective,
      economical, and practical than usual care alone in managing constipation and
      satisfaction with defecation in patients hospitalized with ACS.

PMID- 22847288
TI  - The impact of listening to music on analgesic use and length of hospital stay
      while recovering from laparotomy.
AB  - Postoperative pain management is based on the use of analgesics; however, music
      may alleviate pain either by direct analgesic effects or by relaxing and
      distracting the mind from pain and unpleasant feelings. Conflicting results have
      been presented about how listening to music affects analgesic use and length of
      hospital stay after surgery. We assessed the effect of music listening on
      analgesic use, length of hospital stay, and adverse effects in adult patients
      having laparotomy, using a prospective design with two parallel groups. Patients
      undergoing elective abdominal surgery (n = 168) were assigned to either a music
      group (n = 83) operated on odd weeks or a control group (n = 85) operated on even
      weeks. The music group listened to music 7 times for 30 minutes at a time during
      the first 3 postoperative days. The control group did not listen to the music.
      The hypotheses that patients in the music group will need less analgesic, have a
      shorter length of hospital stay, and experience less adverse effects than those
      in the control group were not supported by the data, although patients recovering
      from surgery enjoyed listening to music. Music listening may enhance quality of
      hospital stay and recovery in patients undergoing major abdominal surgery and
      could be a useful tool to relieve the patient's pain experience.

PMID- 22847290
TI  - Improving treatments for hepatic encephalopathy.

PMID- 22847289
TI  - Differential clinical presentations of Epstein-Barr virus infection and a brief
      literature review.

PMID- 22847291
TI  - Population distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and
      A1298C risk alleles for methotrexate toxicity in Israel.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a central regulatory enzyme in the
      folate pathway. Two non-synonymous single nucleotide polymorphisms in MTHFR,
      C677T (rs1801133) and A1298C (rs1801131) have been associated with reduced MTHFR
      enzyme activity. These polymorphisms, especially C677T, appear to be linked with
      methotrexate-related toxicity, particularly hepatotoxicity; thus, pretreatment
      identification of individuals carrying these polymorphisms may be of clinical
      relevance. The purpose of this study was to determine the frequency and
      distribution of MTHFR polymorphic variants, known to functionally impair MTHFR
      activity, in the highly heterogeneous Israeli population. MTHFR genotyping was
      carried out in the representatives of three major demographic groups in Israel by
      PCR-restriction fragment length polymorphism and high-resolution melting. The
      relative distribution of variant alleles 677T and 1298C was found to be similar
      in individuals of Jewish, Druze and Arab Moslem descent (p = 0.09). However,
      Ashkenazi Jews displayed a 1.9-fold higher frequency of variant 677T and a 1.8
      fold lower frequency of variant 1298C compared to non-Ashkenazi Jews (p < 0.001).
      Distinct differences in the relative frequencies of both polymorphisms were also
      found between Ashkenazi Jews and Druze (p < 0.01 for C677T, p < 0.01 for A1298C)
      or Ashkenazi Jews and Arab Moslem (p < 0.01 for C677T, p < 0.05 for A1298C).
      These data underscore the importance of geographic genetic analysis for a better
      understanding of human pharmacotherapy and personalized medicine.

PMID- 22847292
TI  - Revisiting secondary amyloidosis for an inadequately investigated feature:
      dyslipidemia.
AB  - Secondary amyloidosis is the most frequent form of the systemic amyloidosis
      around the world. Data on frequency and nature of dyslipidemia in patients with
      secondary amyloidosis are not conclusive. We evaluated the lipid abnormalities
      and their association with clinical and laboratory characteristics of the
      patients with secondary amyloidosis. The reports of the kidney biopsies performed
      in our hospital were reviewed. Clinical and laboratory data of the patients with
      biopsy-proven secondary amyloidosis were analyzed retrospectively. A total of 102
      patients were diagnosed as having secondary amyloidosis. Familial Mediterranean
      fever was the leading cause of secondary amyloidosis accounting for 42.2 % of the
      cases. The most frequent indication for kidney biopsy was the nephrotic range
      proteinuria. The most common clinical and laboratory characteristics at the time
      of the diagnosis were edema, proteinuria and impaired renal function. The
      frequency of the nephrotic range proteinuria and microscopic hematuria were 75.5
      and 18.6 %, respectively. Dyslipidemia was found in 88 % of the cases. Serum
      lipids significantly correlated with estimated glomerular filtration rate (eGFR),
      but not with serum albumin or urine protein levels. We demonstrated that majority
      of the patients with secondary amyloidosis had serum lipid abnormalities.
      Dyslipidemia was closely associated with GFR in a manner that patients with
      advanced stage kidney disease had lower serum lipid levels.

PMID- 22847293
TI  - Experimental study of therapy of bone marrow mesenchymal stem cells or muscle
      like cells/calcium alginate composite gel for the treatment of stress urinary
      incontinence.
AB  - OBJECTIVE: To explore the myoblast formation around the urethra and increase in
      urethral resistance of bone marrow mesenchymal stem cells or muscle-like
      cells/calcium alginate composite gel injection therapy and effect on LPP in SUI
      rat model. METHODS: Isolation, cultivation, and identification of SD rat bone
      marrow mesenchymal stem cell were performed. 5-Azacytidine was introduced to
      induce muscle-like cells. SUI was produced in 72 6-week-old female Sprague-Dawley
      rats, which were divided into four groups: stem cell-gel group, muscle-like cell
      gel group, Gel group, and mock control group. One, 4, and 8 weeks after
      injection, the leak point pressure (LPP) was measured. HE staining of Desmin and
      alpha-skeletal muscle actin (alpha-SMA) were performed. RESULTS: At 4 and 8 weeks
      after injection in stem cell-gel group and muscle-like cell-gel group, growth of
      blood vessels gradually increased at gel edge, BMSC, and muscle-like cells
      gathered around the new blood vessels observed by fluorescence tracer, muscle
      like cells grew into elongated spindle-like cells, Desmin, and alpha-SMA staining
      were obviously positive expression. LPP determinations of the mock control group
      compared with the Gel groups were significantly different. CONCLUSIONS: Compound
      of BMSC, muscle-like cells, and calcium alginate composite gel has the potential
      to differentiate into muscle cells in the microenvironment of SUI rat model. It
      is found by LPP measurement that the correlation between the increase in urethral
      resistance and the volume effect of calcium alginate gel is high.

PMID- 22847294
TI  - Overexpression of activated phospholipase Cgamma1 is a risk factor for distant
      metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy.
AB  - Phospholipase Cgamma1 (PLCgamma1) is highly expressed in several tumors. We have
      previously reported that both stable and inducible PLCgamma1 down-regulation
      resulted in an almost complete inhibition of breast cancer-derived experimental
      lung metastasis formation. The aim of our study is to evaluate the association
      between the expression of PLCgamma1 and of PLCgamma1 phosphorylated at Tyr1253
      (PLCgamma1-pY1253) and at Tyr783 (PLCgamma1-pY783) with the clinical outcome of
      patients with node negative, T1/T2 breast cancers. The study groups consisted of
      292 (training set) and 122 (validation set) patients presenting with primary
      unilateral breast carcinoma (T1-T2), with no evidence of nodal involvement and
      distant metastases. PLCgamma1, PLCgamma1-pY1253 and PLCgamma1-pY783 protein
      expression were assessed by immunohistochemistry on tissue microarrays and the
      results correlated with the clinical data using Kaplan-Meier curves and
      multivariate Cox regression analysis. Tumor cells while expressing variable
      proportions of cytoplasmic PLCgamma1, express PLCgamma1-pY1253 and PLCgamma1
      pY783 predominantly in the nucleus. High expression of PLCgamma1, and of its
      activated forms, is associated with a worse clinical outcome in terms of
      incidence of distant metastases, and not of local relapse in T1-T2, N0 breast
      cancer patients undergone adjuvant chemotherapy. PLCgamma1 over-expression
      appears to be a reliable predictive surrogate marker of development of
      metastases. Thus, targeting PLCgamma1 pathways might represent a potential
      therapeutic approach for the prevention of metastatic disease in breast cancer.

PMID- 22847295
TI  - A possible cross-talk between autophagy and apoptosis in generating an immune
      response in melanoma.
AB  - Melanoma is the most aggressive form of skin cancer, responsible for the majority
      of skin cancer related deaths. Thus, the search for natural molecules which can
      effectively destroy tumors while promoting immune activation is essential for
      designing novel therapies against metastatic melanoma. Here, we report for the
      first time that a natural triterpenoid, Ganoderic acid DM (GA-DM), induces an
      orchestrated autophagic and apoptotic cell death, as well as enhanced
      immunological responses via increased HLA class II presentation in melanoma
      cells. Annexin V staining and flow cytometry showed that GA-DM treatment induced
      apoptosis of melanoma cells, which was supported by a detection of increased Bax
      proteins, co-localization and elevation of Apaf-1 and cytochrome c, and a
      subsequent cleavage of caspases 9 and 3. Furthermore, GA-DM treatment initiated a
      possible cross-talk between autophagy and apoptosis as evidenced by increased
      levels of Beclin-1 and LC3 proteins, and their timely interplay with apoptotic
      and/or anti-apoptotic molecules in melanoma cells. Despite GA-DM's moderate
      cytotoxicity, viable cells expressed high levels of HLA class II proteins with
      improved antigen presentation and CD4+ T cell recognition. The antitumor efficacy
      of GA-DM was also investigated in vivo in murine B16 melanoma model, where GA-DM
      treatment slowed tumor formation with a significant reduction in tumor volume.
      Taken together, these findings demonstrate the potential of GA-DM as a natural
      chemo-immunotherapeutic capable of inducing a possible cross-talk between
      autophagy and apoptosis, as well as improved immune recognition for sustained
      melanoma tumor clearance.

PMID- 22847296
TI  - Mechanistic analysis of solute transport in an in vitro physiological two-phase
      dissolution apparatus.
AB  - In vitro dissolution methodologies that adequately capture the oral
      bioperformance of solid dosage forms are critical tools needed to aid formulation
      development. Such methodologies must encompass important physiological parameters
      and be designed with drug properties in mind. Two-phase dissolution apparatuses,
      which contain an aqueous phase in which the drug dissolves (representing the
      dissolution/solubility component) and an organic phase into which the drug
      partitions (representing the absorption component), have the potential to provide
      meaningful predictions of in vivo oral bioperformance for some BCS II, and
      possibly some BCS IV drug products. Before such an apparatus can be evaluated
      properly, it is important to understand the kinetics of drug substance
      partitioning from the aqueous to the organic medium. A mass transport analysis
      was performed of the kinetics of partitioning of drug substance solutions from
      the aqueous to the organic phase of a two-phase dissolution apparatus. Major
      assumptions include pseudo-steady-state conditions, a dilute aqueous solution and
      diffusion-controlled transport. Input parameters can be measured or estimated a
      priori. This paper presents the theory and derivation of our analysis, compares
      it with a recent kinetic approach, and demonstrates its effectiveness in
      predicting in vitro partitioning profiles of three BCS II weak acids in four
      different in vitro two-phase dissolution apparatuses. Very importantly, the paper
      discusses how a two-phase apparatus can be scaled to reflect in vivo absorption
      kinetics and for which drug substances the two-phase dissolution systems may be
      appropriate tools for measuring oral bioperformance.

PMID- 22847297
TI  - Broad autism phenotype in typically developing children predicts performance on
      an eye-tracking measure of joint attention.
AB  - We examined visual attention allocation during a set of social videos that are
      intended to elicit the coordination of attention with another person, compared to
      a control condition. Deficits in joint attention are a characteristic of young
      children with autism spectrum disorder (ASD). Participants included a diverse
      sample of 50 typically developing school-aged children between 3 and 9 years of
      age (M = 6:3, SD = 1:8). Results demonstrated that gaze allocation differed
      significantly between the experimental and control condition. Further, individual
      differences in gaze allocation were significantly predicted by a parent-report
      measure evaluating features of the broad autism phenotype. This study contributes
      to a research program that aims to develop and validate an endophenotype measure
      of ASD.

PMID- 22847299
TI  - Liver: Transjugular liver biopsy yields high-quality samples.

PMID- 22847298
TI  - Altered expression of TNFSF4 and TRAF2 mRNAs in peripheral blood mononuclear
      cells in patients with systemic lupus erythematosus: association with
      atherosclerotic symptoms and lupus nephritis.
AB  - OBJECTIVES: This study compares the expression levels of tumor necrosis factor
      ligand superfamily member 4 (TNFSF4) and TNF-R-associated factor 2 (TRAF2) mRNAs
      in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus
      erythematosus (SLE) against healthy controls. The association of SLE disease
      activity index (SLEDAI) and clinical features of SLE with altered expression
      levels of TNFSF4 and TRAF2 mRNAs were also evaluated. DESIGN: We used real-time
      reverse transcription polymerase chain reaction to measure TNFSF4 and TRAF2 mRNAs
      expression levels in peripheral blood mononuclear cells of 57 SLE patients and 57
      healthy controls. RESULTS: The expression level of TNFSF4 mRNA was significantly
      higher in SLE patients than in the control group. Overexpression of TNFSF4 was
      correlated with arthritis, atherosclerosis and lupus nephritis. TRAF2 mRNA was
      underexpressed in PBMCs of SLE patients, and its lower expression was associated
      with atherosclerosis and lupus nephritis. The altered expression levels of TNFSF4
      and TRAF2 mRNAs was significantly correlated with SLEDAI. CONCLUSION: Our results
      suggest that changes in the expression levels of TNFSF4 and TRAF2 mRNAs may
      significantly correlate with the pathogenesis of SLE, the disease activity and
      different clinical features of lupus, particularly lupus nephritis,
      atherosclerosis and arthritis.

PMID- 22847300
TI  - Hepatitis: Vitamin B12 increases the sustained virological response in HCV.

PMID- 22847301
TI  - A pillared metal-organic framework incorporated with 1,2,3-triazole moieties
      exhibiting remarkable enhancement of CO2 uptake.
AB  - The replacement of the pillar ligand, 4,4'-bipyridine, in the prototypal pillared
      MOF, MOF-508, with the custom-designed ligand, 4,4'-(2H-1,2,3-triazole-2,4
      diyl)dipyridine, affords a porous metal-triazolate framework, MTAF-3, which
      demonstrates remarkable enhancement of CO(2) uptake capacity by a factor of ~3
      compared to the parent MOF-508.

PMID- 22847302
TI  - Tumor-specific targeting with modified Sindbis viral vectors: evaluation with
      optical imaging and positron emission tomography in vivo.
AB  - PURPOSE: Sindbis virus (SINV) infect tumor cells specifically and systemically
      throughout the body. Sindbis vectors are capable of expressing high levels of
      transduced suicide genes and thus efficiently produce enzymes for prodrug
      conversion in infected tumor cells. The ability to monitor suicide gene
      expression levels and viral load in patients, after administration of the
      vectors, would significantly enhance this tumor-specific therapeutic option.
      PROCEDURES: The tumor specificity of SINV is mediated by the 67-kDa laminin
      receptor (LR). We probed different cancer cell lines for their LR expression and,
      to determine the specific role of LR-expression in the infection cycle, used
      different molecular imaging strategies, such as bioluminescence, fluorescence
      molecular tomography, and positron emission tomography, to evaluate SINV-mediated
      infection in vitro and in vivo. RESULTS: All cancer cell lines showed a marked
      expression of LR. The infection rates of the SINV particles, however, differed
      significantly among the cell lines. CONCLUSION: We used novel molecular imaging
      techniques to visualize vector delivery to different neoplatic cells. SINV
      infection rates proofed to be not solely dependent on cellular LR expression.
      Further studies need to evaluate the herein discussed ways of cellular infection
      and viral replication.

PMID- 22847303
TI  - Allogeneic stem cell transplantation for patients with chronic myeloid leukemia:
      risk stratified approach with a long-term follow-up.
AB  - The use of allogeneic stem cell transplantation (SCT) for chronic myeloid
      leukemia (CML) was almost abandoned in recent years for very effective targeted
      therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third
      of patients still need another treatment including SCT. 38 consecutive CML
      patients were treated (most in preimatinib era) with allogeneic SCT, using
      partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI),
      without post-transplant graft-versus-host disease (GvHD) prophylaxis.
      Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and
      fludarabine followed by donor stem cell transfusion. With a median follow up of
      90.5 months (1-134), 32 patients are alive. 97% engrafted. 5-year leukemia free
      survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All
      patients are in major molecular remission and 78% in complete molecular
      remission. Transplant-related mortality (TRM) was 13%. Twenty-four patients
      received DLI for residual disease. Acute GvHD, mostly Grades I-II, occurred in
      18% of patients post-transplant and in 24% of patients receiving DLI. In
      conclusion, the risk-adapted approach using only partial TCD and preemptive
      escalated dose of DLI precluded the need for immunosuppressive medications and
      reduced the risk of significant GvHD without compromising engraftment and long
      term disease control. Am. J. Hematol. 2012. (c) 2012 Wiley Periodicals, Inc.

PMID- 22847304
TI  - A practical approach to achieve private medical record linkage in light of public
      resources.
AB  - OBJECTIVE: Integration of patients' records across resources enhances analytics.
      To address privacy concerns, emerging strategies such as Bloom filter encodings
      (BFEs), enable integration while obscuring identifiers. However, recent
      investigations demonstrate BFEs are, in theory, vulnerable to cryptanalysis when
      encoded identifiers are randomly selected from a public resource. This study
      investigates the extent to which cryptanalysis conditions hold for (1) real
      patient records and (2) a countermeasure that obscures the frequencies of the
      identifying values in encoded datasets. DESIGN: First, to investigate the
      strength of cryptanalysis for real patient records, we build BFEs from
      identifiers in an electronic medical record system and apply cryptanalysis using
      identifiers in a publicly available voter registry. Second, to investigate the
      countermeasure under ideal cryptanalysis conditions, we compose BFEs from the
      identifiers that are randomly selected from a public voter registry. MEASUREMENT:
      We utilize precision (ie, rate of correct re-identified encodings) and
      computation efficiency (ie, time to complete cryptanalysis) to assess the
      performance of cryptanalysis in BFEs before and after application of the
      countermeasure. RESULTS: Cryptanalysis can achieve high precision when the
      encoded identifiers are composed of a random sample of a public resource (ie, a
      voter registry). However, we also find that the attack is less efficient and may
      not be practical for more realistic scenarios. By contrast, the proposed
      countermeasure made cryptanalysis impractical in terms of precision and
      efficiency. CONCLUSIONS: Performance of cryptanalysis against BFEs based on
      patient data is significantly lower than theoretical estimates. The proposed
      countermeasure makes BFEs resistant to known practical attacks.

PMID- 22847306
TI  - Consumer experience with and attitudes toward health information technology: a
      nationwide survey.
AB  - Electronic health records (EHR) are becoming more common because of the federal
      EHR incentive programme, which is also promoting electronic health information
      exchange (HIE). To determine whether consumers' attitudes toward EHR and HIE are
      associated with experience with doctors using EHR, a nationwide random-digit-dial
      survey was conducted in December 2011. Of 1603 eligible people contacted, 1000
      (63%) participated. Most believed EHR and HIE would improve healthcare quality
      (66% and 79%, respectively). Respondents whose doctor had an EHR were more likely
      to believe that these technologies would improve quality (for EHR, OR 2.3; for
      HIE, OR 1.7). However, experience with physicians using EHR was not associated
      with privacy concerns. Consumers whose physicians use EHR were more likely to
      believe that EHR and HIE will improve healthcare when compared to others.
      However, experience with a physician using an EHR had no relationship with
      privacy concerns.

PMID- 22847305
TI  - Use of the internet and an online personal health record system by US veterans:
      comparison of Veterans Affairs mental health service users and other veterans
      nationally.
AB  - OBJECTIVE: The Department of Veterans Affairs (VA) operates one of the largest
      nationwide healthcare systems and is increasing use of internet technology,
      including development of an online personal health record system called My
      HealtheVet. This study examined internet use among veterans in general and
      particularly use of online health information among VA patients and specifically
      mental health service users. METHODS: A nationally representative sample of 7215
      veterans from the 2010 National Survey of Veterans was used. Logistic regression
      was employed to examine background characteristics associated with internet use
      and My HealtheVet. RESULTS: 71% of veterans reported using the internet and about
      a fifth reported using My HealtheVet. Veterans who were younger, more educated,
      white, married, and had higher incomes were more likely to use the internet.
      There was no association between background characteristics and use of My
      HealtheVet. Mental health service users were no less likely to use the internet
      or My HealtheVet than other veterans. DISCUSSION: Most veterans are willing to
      access VA information online, although many VA service users do not use My
      HealtheVet, suggesting more education and research is needed to reduce barriers
      to its use. CONCLUSION: Although adoption of My HealtheVet has been slow, the
      majority of veterans, including mental health service users, use the internet and
      indicate a willingness to receive and interact with health information online.

PMID- 22847307
TI  - When 'technically preventable' alerts occur, the design--not the prescriber--has
      failed.

PMID- 22847308
TI  - The evolution of the treatment of esophageal achalasia: a look at the last two
      decades.
AB  - Thanks to the development of minimally invasive surgery, the last 20 years have
      witnessed a revolution in the treatment of benign esophageal disorders,
      particularly for esophageal achalasia. This has brought a shift in the treatment
      algorithm of this disease, as today a laparoscopic Heller myotomy with partial
      fundoplication is considered the primary form of treatment in most Centers in
      North America. This article reviews the evolution of the treatment of esophageal
      achalasia during the last two decades, with particular stress on the key
      technical elements of this operation.

PMID- 22847314
TI  - On the relationship between molecular state and single electron pictures in
      simple electrochemical junctions.
AB  - We consider a molecular conduction junction that comprises a redox molecule
      bridging between metal electrodes, in the limit of weak coupling and high
      temperature where electron transport is dominated by Marcus electron transfer
      kinetics. We address the correspondence between the Marcus description in terms
      of nuclear potential energy surfaces associated with different charging states of
      the molecular bridge, and the single electron description commonly used in
      theories of molecular conduction. The relationship between the energy gap,
      reorganization energy and activation energy parameters of the Marcus theory and
      the corresponding energy parameters in the single electron description is
      elucidated. We point out that while transport in the normal Marcus regime
      involves activated (therefore relatively slow) transitions between at least two
      charging states of the molecular bridge, deep in the inverted regime only one of
      these states is locally stable and transitions into this state are
      activationless. The relatively slow rates that characterize the normal Marcus
      transport regime manifest themselves in the appearance of hysteresis in the
      system transport behavior as a function of gate or bias potentials for relatively
      slow scan rates of these potentials, but not bistability in the junction
      conduction behavior. We also consider the limit of fast solvent reorganization
      that may reflect the response of the electronic environment (electronic
      polarization of a solvent and of the metal electrodes) to the changing charging
      state of the bridge. In this limit, environmental reorganization appears as
      renormalization of the bridge electronic energy levels. We show that the effect
      of this reorganization on the junction conduction properties is not universal and
      depends on the particular bridge charging states that are involved in the
      conduction process.

PMID- 22847317
TI  - Bisphosphonates and colon cancer: reply.

PMID- 22847316
TI  - 1,5-Anhydroglucitol in diabetes mellitus.
AB  - The measure of glycated hemoglobin (HbA1c) concentration is the gold standard of
      glycemic control index in diabetes management and is well known as a marker for
      diabetes complications. However, HbA1c level neither accurately reflect glucose
      fluctuations, nor does it provide a clear indication of glycemic control in
      recent days or weeks. HbA1c concentration measurement can be confounded in
      patients with anemia, hemoglobinopathy, liver disease, or renal impairment. 1,5
      Anhydroglucitol (1,5-AG) structurally resembles glucose. It can be influenced by
      diet or medication, gender and race, especially severe renal disease and various
      pathological conditions. Most notably, 1,5-AG level is reflective of short-term
      glucose status, postprandial hyperglycemia, and glycemic variability which are
      not captured by HbA1c assay. 1,5-AG may suggest an alternative index of subtypes
      of diabetes and a warning sign of diabetes complications. This review provides an
      overview of our current understanding of the role of 1,5-AG marker in diabetes.
      However, further investigations on the associations between this glycemic marker
      and diabetes complications are needed.

PMID- 22847318
TI  - Does it work in the long term?--A systematic review on pelvic floor muscle
      training for female stress urinary incontinence.
AB  - AIMS: There is level 1, grade A evidence that pelvic floor muscle training (PFMT)
      is effective in treatment of stress urinary incontinence (SUI), but long-term
      outcome has been questioned. The aim of this systematic review was to evaluate
      the long-term outcome of PFMT for female SUI. METHODS: Computerized search on
      PubMed up to year 2012 was undertaken with the search strategy: pelvic floor AND
      (urinary incontinence OR stress urinary incontinence) AND (training OR exercise
      OR physical activity) AND (follow-up OR long-term). Limitations were: humans,
      female, clinical trial, English, and adults. Inclusion criteria were: studies on
      SUI using PFMT with or without biofeedback as the intervention, follow-up period
      of >=1 year. Exclusion criteria were studies using electrical stimulation alone
      and studies in the peripartum period. RESULTS: Nineteen studies were included
      (1,141 women followed between 1 and 15 years). Statistical meta-analysis was not
      performed due to high heterogeneity. Only two studies provided follow-up
      interventions. Losses to follow-up during the long-term period ranged between 0%
      and 39%. Long-term adherence to PFMT varied between 10% and 70%. Five studies
      reported that the initial success rate on SUI and MUI was maintained at long
      term. Long-term success based on responders to the original trial varied between
      41% and 85%. Surgery rates at long term varied between 4.9% and 58%. CONCLUSIONS:
      Short-term outcome of PFMT can be maintained at long-term follow-up without
      incentives for continued training, but there is a high heterogeneity in both
      interventional and methodological quality in short-and long-term pelvic floor
      muscle training studies.

PMID- 22847319
TI  - Assessing the bioequivalence of topical retinoid products by pharmacodynamic
      assay.
AB  - PURPOSE: To develop a simple pharmacodynamic (PD) assay for the evaluation of the
      bioequivalence of topically applied retinoid products. METHODS: Daily
      applications of products containing tretinoin or adapalene were made to the
      forearms of human subjects for up to 21 days. Percutaneous absorption was
      enhanced through the use of polyethylene film occlusion (5 h). Pharmacologic
      activity was assessed through the daily measurement of three cutaneous responses
      intimately linked to retinoid-induced changes in epidermal differentiation: (1)
      erythema; (2) exfoliation (scaling/peeling), and (3) increased transepidermal
      water loss. RESULTS: The PD model exhibited the sensitivity and specificity
      required to function as a bioequivalence surrogate. It was possible to
      differentiate between: (1) three concentrations of tretinoin in a commercial
      cream product line; (2) two concentrations of tretinoin in a commercial gel
      product line; (3) different vehicles (gel vs. cream) containing the same
      concentration of tretinoin, and (4) tretinoin and adapalene at the same
      concentration. The applicability of this model for bioequivalence testing was
      established by showing that it had sufficient power to determine that three test
      tretinoin cream products and two approved generic tretinoin gel products were
      equivalent to their corresponding reference products. CONCLUSIONS: A surrogate PD
      model to assess retinoid bioequivalence has been developed.

PMID- 22847320
TI  - Vestibular disease: anatomy, physiology, and clinical signs.
AB  - The vestibular system is responsible for keeping an animal oriented with respect
      to gravity. It is a sensory system that maintains the position of the eyes, body,
      and limbs in reference to the position of the head. Proper interpretation of
      neurologic deficits and precise neuroanatomic localization are essential to
      diagnose and prognosticate the underlying disorder. Neurologic examination can
      confirm whether the vestibular dysfunction is of peripheral or central nervous
      system origin. Idiopathic vestibular syndrome is the most common cause of
      peripheral vestibular disease in dogs and, despite its dramatic clinical
      presentation, can improve without intervention. Central vestibular diseases
      generally have a poorer prognosis.

PMID- 22847321
TI  - Vestibular disease: diseases causing vestibular signs.
AB  - Having determined whether a patient has central or peripheral vestibular disease,
      clinicians must then determine what diseases are likely to result in such a
      presentation. This article describes the more common diseases causing vestibular
      disease in dogs and cats. Having formulated a list of potential causes of
      vestibular disease, clinicians should proceed through a systematic investigation
      to diagnose the underlying condition. A companion article describes the anatomy,
      physiology, and clinical signs associated with vestibular disease.

PMID- 22847322
TI  - Brachycephalic airway syndrome: pathophysiology and diagnosis.
AB  - Brachycephalic airway syndrome (BAS) is a group of abnormalities that result in
      upper airway obstruction. Primary malformations include stenotic nares, elongated
      soft palate, and hypoplastic trachea, which cause an increase in negative
      pressure within the upper airways that can eventually lead to secondary
      abnormalities such as everted laryngeal saccules, everted tonsils, and laryngeal
      and tracheal collapse. Abnormal nasopharyngeal turbinates are also encountered,
      but have not been classified as primary or secondary. BAS is readily diagnosed,
      and quality of life is improved with appropriate medical and/or surgical
      management.

PMID- 22847323
TI  - Equine distal limb wounds: new and emerging treatments.
AB  - Distal limb wounds occur commonly in horses, and treatment can be frustrating for
      owners and veterinarians. Caring for these wounds is often very expensive, labor
      intensive, and prolonged. Many commercial products and clinical techniques have
      been developed to help treat these wounds. Healing of these wounds depends on
      many factors. With proper wound evaluation and treatment, affected horses can
      return to function sooner than in the past.

PMID- 22847324
TI  - Excellence in exotics: Fish nutrition and related problems.
AB  - Nutritional diseases in pet fish are quite common, either as primary or secondary
      problems. However, determining the definitive diagnosis of nutritional problems
      is often difficult. Knowledge regarding the natural history of the fish (e.g.,
      herbivore vs. carnivore) is essential in the clinical workup.

PMID- 22847325
TI  - Excellence in exotics: Treatment of diseases in pond fish.
AB  - Intensive fish medicine is a growing area within the veterinary profession as
      more people are requesting a similar level of care for their fish as they expect
      for their dogs and cats. Well-informed clients can be of great assistance during
      the clinical workup. A teamwork approach to fish husbandry, nutrition, and
      medicine between the owner and veterinarian will yield the most satisfying and
      successful health care results.

PMID- 22847326
TI  - Focus on nutrition: Nutritional management of protein-losing nephropathy in dogs.
AB  - Optimal treatment of protein-losing nephropathy (PLN) should address both medical
      and nutritional issues. In nonazotemic dogs with PLN, the main nutrients of
      concern are protein, calories, omega-3 fatty acids, and sodium. In azotemic dogs
      with PLN, requirements for additional nutrients should be addressed. The amount
      of protein and the specific diet must be individualized for every patient with
      PLN because commercial dog foods differ greatly in protein and other nutrients.
      It is critical to avoid excessive dietary protein restriction, which may
      contribute to loss of lean body mass. A thorough diet history must be obtained to
      account for the animal's entire daily intake of protein and other nutrients.

PMID- 22847327
TI  - Intussusception in horses.
AB  - Intussusception is thought to be associated with abnormal motility in the
      intestinal tract. The clinical signs vary depending on the associated intestinal
      damage. Therefore, intussusception should be included in the differential
      diagnosis for any horse with acute or chronic colic. A diagnosis may be made by
      ultrasonography or rectal palpation, but exploratory laparotomy is the
      predominant method. Treatment varies according to the location of the
      intussusception, but all treatments involve surgical intervention. The prognosis
      for intussusception can be good if the condition is diagnosed and treated
      promptly.

PMID- 22847328
TI  - Video-oculography in mice.
AB  - Eye movements are very important in order to track an object or to stabilize an
      image on the retina during movement. Animals without a fovea, such as the mouse,
      have a limited capacity to lock their eyes onto a target. In contrast to these
      target directed eye movements, compensatory ocular eye movements are easily
      elicited in afoveate animals. Compensatory ocular movements are generated by
      processing vestibular and optokinetic information into a command signal that will
      drive the eye muscles. The processing of the vestibular and optokinetic
      information can be investigated separately and together, allowing the
      specification of a deficit in the oculomotor system. The oculomotor system can be
      tested by evoking an optokinetic reflex (OKR), vestibulo-ocular reflex (VOR) or a
      visually-enhanced vestibulo-ocular reflex (VVOR). The OKR is a reflex movement
      that compensates for "full-field" image movements on the retina, whereas the VOR
      is a reflex eye movement that compensates head movements. The VVOR is a reflex
      eye movement that uses both vestibular as well as optokinetic information to make
      the appropriate compensation. The cerebellum monitors and is able to adjust these
      compensatory eye movements. Therefore, oculography is a very powerful tool to
      investigate brain-behavior relationship under normal as well as under
      pathological conditions (f.e. of vestibular, ocular and/or cerebellar origin).
      Testing the oculomotor system, as a behavioral paradigm, is interesting for
      several reasons. First, the oculomotor system is a well understood neural system.
      Second, the oculomotor system is relative simple; the amount of possible eye
      movement is limited by its ball-in-socket architecture ("single joint") and the
      three pairs of extra-ocular muscles. Third, the behavioral output and sensory
      input can easily be measured, which makes this a highly accessible system for
      quantitative analysis. Many behavioral tests lack this high level of quantitative
      power. And finally, both performance as well as plasticity of the oculomotor
      system can be tested, allowing research on learning and memory processes.
      Genetically modified mice are nowadays widely available and they form an
      important source for the exploration of brain functions at various levels. In
      addition, they can be used as models to mimic human diseases. Applying
      oculography on normal, pharmacologically-treated or genetically modified mice is
      a powerful research tool to explore the underlying physiology of motor behaviors
      under normal and pathological conditions. Here, we describe how to measure video
      oculography in mice.

PMID- 22847329
TI  - Temperature and species richness effects in phytoplankton communities.
AB  - Phytoplankton play an important role as primary producers and thus can affect
      higher trophic levels. Phytoplankton growth and diversity may, besides other
      factors, be controlled by seasonal temperature changes and increasing water
      temperatures. In this study, we investigated the combined effects of temperature
      and diversity on phytoplankton growth. In a controlled laboratory experiment,
      monocultures of 15 freshwater phytoplankton taxa (green algae, cyanobacteria, and
      diatoms) as well as 25 mixed communities of different species richness (2-12
      species) and taxa composition were exposed to constant temperatures of 12, 18,
      and 24  degrees C. Additionally, they were exposed to short-term daily
      temperature peaks of +4  degrees C. Increased species richness had a positive
      effect on phytoplankton growth rates and phosphorous content at all temperature
      levels, with maximum values occurring at 18  degrees C. Overyielding was observed
      at almost all temperature levels and could mostly be explained by complementary
      traits. Higher temperatures resulted in higher fractions of cyanobacteria in
      communities. This negative effect of temperature on phytoplankton diversity
      following a shift in community composition was most obvious in communities
      adapted to cooler temperatures, pointing to the assumption that relative
      temperature changes may be more important than absolute ones.

PMID- 22847330
TI  - Role of AGC kinases in plant growth and stress responses.
AB  - AGC kinases are important regulators of cell growth, metabolism, division, and
      survival in mammalian systems. Mutation or deregulation of members of this family
      of protein kinases contribute to the pathogenesis of many human diseases,
      including cancer and diabetes. Although AGC kinases are conserved in the plant
      kingdom, little is known about their molecular functions and targets. Some of the
      best-studied plant AGC kinases mediate auxin signaling and are thereby involved
      in the regulation of growth and morphogenesis. Furthermore, certain members are
      regulated by lipid-derived signals via the 3-phosphoinositide-dependent kinase 1
      (PDK1) and the kinase target of rapamycin (TOR), similar to its animal
      counterparts. In this review, we discuss recent findings on plant AGC kinases
      that unravel important roles in the regulation of plant growth, immunity and cell
      death, and connections to stress-induced mitogen-activated protein kinase
      signaling cascades.

PMID- 22847332
TI  - Inflammation in muscular dystrophy and the beneficial effects of non-steroidal
      anti-inflammatory drugs.
AB  - INTRODUCTION: Glucocorticoids are the only drugs available for the treatment of
      Duchenne muscular dystrophy (DMD), but it is unclear whether their efficacy is
      dependent on their anti-inflammatory activity. METHODS: To address this issue,
      mdx mice were treated daily with methylprednisolone and non-steroidal anti
      inflammatory drugs (NSAIDs: aspirin, ibuprofen, parecoxib). RESULTS: NSAID
      treatment was effective in ameliorating muscle morphology and reducing macrophage
      infiltration and necrosis. The percentage of regenerating myofibers was not
      modified by the treatments. The drugs were effective in reducing COX-2 expression
      and inflammatory cytokines, but they did not affect utrophin levels. The effects
      of the treatments on contractile performance were analyzed. Isometric tension did
      not differ in treated and untreated muscle, but the resistance to fatigue was
      decreased by treatment with methylprednisolone and aspirin. CONCLUSIONS: NSAIDs
      have a beneficial effect on mdx muscle morphology, pointing to a crucial role of
      inflammation in the progression of DMD.

PMID- 22847333
TI  - LC-MS-based chemotaxonomic classification of wild-type Lespedeza sp. and its
      correlation with genotype.
AB  - In this study, 39 specimens belonging to Lespedeza species (Lespedeza
      cyrtobotrya, L. bicolor, L. maximowiczii, and Lespedeza cuneata) (Leguminosae)
      were classified phenotypically and genotypically. We constructed a phylogenetic
      tree based on the combined nrDNA (internal transcribed spacer; ITS) and cpDNA
      (trnL-trnF) sequences with the aim of classifying the genotypes. Samples were
      mainly divided into three genotypes. Samples of L. cyrtobotrya and L. bicolor
      were mixed in a single branch, whereas samples of L. maximowiczii and L. cuneata
      were clustered within species, respectively. We performed a liquid chromatography
      electrospray ionization-mass spectrometry-based metabolite profiling analysis to
      classify the phenotypes. Multivariate statistical analyses such as principal
      component analysis (PCA) and hierarchical clustering analysis (HCA) were used for
      the clustering pattern analysis and distance analysis between species,
      respectively. According to the PCA and HCA results, leaves were classified into
      four phenotypes according to species. In both the genetic and chemotaxonomic
      classification methods, the distance between L. cyrtobotrya and L. bicolor was
      the closest between species, and L. cuneata was the farthest away from the other
      three species. Additionally, orthogonal partial least squares-discriminant
      analysis was employed to identify significantly different phytochemicals between
      species. We classified L. cyrtobotrya and L. bicolor by identifying significantly
      different phytochemicals. Interestingly, leaves and stems showed different
      phenotypic classifications based on the chemotaxonomic classification. Stem
      samples of the other three species were mixed regardless of species, whereas L.
      cyrtobotrya stem samples were clustered within species. The phenotypic
      classification of leaves coincided more with the genotypic classification than
      that of stems. Key message We classified four wild-type Lespedeza sp. by
      analyzing the combined nrDNA (ITS) and cpDNA (trnL-trnF) sequences. We also
      classified leaves and stems of Lespedeza sp. by applying liquid chromatography
      mass spectroscopy-based metabolite profiling.

PMID- 22847335
TI  - Exploring the properties of small molecule protein binding via molecular
      simulations: the TRSH-p53 core domain complex.
AB  - Molecular dynamics simulations have been performed to investigate the binding of
      tris(hydroxymethyl)-aminomethane to the surface of the core domain of the mouse
      cellular tumor antigen p53 employing the GROMOS  and 53A6 force field parameter
      sets. A close investigation of the crystal structure reported by Ho et al.
      revealed that the protonated form is bound to the protein, i.e. a
      tris(hydroxymethyl)-methylammonium ion (TRSH). Molecular Dynamics (MD)
      simulations indicate that the p53 protein gains stability upon binding the
      ligand. In addition to MD simulations of the p53 protein with and without the
      TRSH compound, thermodynamic integration was utilised to estimate the free
      enthalpy of binding of the TRSH-p53 complex, which was estimated to be -49 and 
      54 kJ mol(-1) utilising the  and 53A6 force fields, respectively.

PMID- 22847331
TI  - Cross-presentation of IgG-containing immune complexes.
AB  - IgG is a molecule that functionally combines facets of both innate and adaptive
      immunity and therefore bridges both arms of the immune system. On the one hand,
      IgG is created by adaptive immune cells, but can be generated by B cells
      independently of T cell help. On the other hand, once secreted, IgG can rapidly
      deliver antigens into intracellular processing pathways, which enable efficient
      priming of T cell responses towards epitopes from the cognate antigen initially
      bound by the IgG. While this process has long been known to participate in CD4(+)
      T cell activation, IgG-mediated delivery of exogenous antigens into a major
      histocompatibility complex (MHC) class I processing pathway has received less
      attention. The coordinated engagement of IgG with IgG receptors expressed on the
      cell-surface (FcgammaR) and within the endolysosomal system (FcRn) is a highly
      potent means to deliver antigen into processing pathways that promote cross
      presentation of MHC class I and presentation of MHC class II-restricted epitopes
      within the same dendritic cell. This review focuses on the mechanisms by which
      IgG-containing immune complexes mediate such cross-presentation and the
      implications that this understanding has for manipulation of immune-mediated
      diseases that depend upon or are due to the activities of CD8(+) T cells.

PMID- 22847334
TI  - VpWRKY3, a biotic and abiotic stress-related transcription factor from the
      Chinese wild Vitis pseudoreticulata.
AB  - Chinese wild grapevine Vitis pseudoreticulata accession 'Baihe-35-1' is
      identified as the precious resource with multiple resistances to pathogens. A
      directional cDNA library was constructed from the young leaves inoculated with
      Erysiphe necator. A total of 3,500 clones were sequenced, yielding 1,727
      unigenes. Among them, 762 unigenes were annotated and classified into three
      classes, respectively, using Gene Ontology, including 22 ESTs related to
      transcription regulator activity. A novel WRKY transcription factor was isolated
      from the library, and designated as VpWRKY3 (GenBank Accession No. JF500755). The
      full-length cDNA is 1,280 bp, encoding a WRKY protein of 320 amino acids. VpWRKY3
      is localized to nucleus and functions as a transcriptional activator. QRT-PCR
      analysis showed that the VpWRKY3 specifically accumulated in response to
      pathogen, salicylic acid, ethylene and drought stress. Overexpression of VpWRKY3
      in tobacco increased the resistance to Ralstonia solanacearum, indicating that
      VpWRKY3 participates in defense response. Furthermore, VpWRKY3 is also involved
      in abscisic acid signal pathway and salt stress. This experiment provided an
      important basis for understanding the defense mechanisms mediated by WRKY genes
      in China wild grapevine. Generation of the EST collection from the cDNA library
      provided valuable information for the grapevine breeding. Key message We
      constructed a cDNA library from Chinese wild grapevine leaves inoculated with
      powdery mildew. VpWRKY3 was isolated and demonstrated that it was involved in
      biotic and abiotic stress responses.

PMID- 22847336
TI  - Occurrence and fate of perfluorinated compounds in sewage sludge from Spain and
      Germany.
AB  - Perfluorinated compounds (PFCs) are persistent and bioaccumulative organic
      compounds used as additives in many industrial products. After use, these
      compounds enter wastewater treatment plants (WWTP) and long-chain PFCs are
      primarily accumulated in sludge. The aim of this study was to determine the
      occurrence and behavior of five PFCs in sludge from 15 WWTP from Spain and
      Germany that receive both urban and industrial wastes. The PFCs studied were
      perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS),
      perfluorobutanesulfonate (PFBS), perfluorooctanoic acid (PFOA), and
      perfluorononanoic acid (PFNA). One gram of freeze-dried, sieved, and homogenized
      sludge was extracted using an ultrasonic bath with methanol and glacial acetic
      acid. After that, the extract was recovered and evaporated to dryness with a
      TurboVap and then 1 mL of acetonitrile was added and the extract was cleaned up
      with black carbon. Liquid chromatography coupled to mass spectrometry operated in
      selected reaction monitoring was used to determine target compounds. Quality
      parameters are provided for the set of compounds studied. PFCs were detected in
      all samples. In Spanish sludge, ?PFC ranged from 0.28 to 5.20 ng/g dry weight
      (dw) with prevalence of PFOS, while in German sludge, ?PFC ranged from 20.7 to
      38.6 ng/g dw and PFBS was the dominant compound. As a next step, the evolution of
      PFC concentrations within the sludge treatment steps (primary sludge, anaerobic
      digested sludge, and centrifuged sludge) was evaluated and differences among
      levels and patterns were observed and were attributed to the influent water
      quality and treatment used. Finally, we estimated the amount of PFCs discharged
      via sludge in order to determine the potential impact to the environment
      according to different sludge usage practices in the two regions investigated.
      This manuscript provided an intra-European overview of PFC distribution in
      sludge. Levels and compound distribution depend on the WWTP sampled. This study
      demonstrates that PFCs are persistent to sludge treatment and the loads in sludge
      may pose a future environmental risk, if not controlled.

PMID- 22847338
TI  - Where have all the cell lines gone?

PMID- 22847339
TI  - Twist viscosities and flow alignment of biaxial nematic liquid crystal phases of
      a soft ellipsoid-string fluid studied by molecular dynamics simulation.
AB  - We have calculated the twist viscosity and the alignment angle between the
      director and the stream lines in shear flow of a liquid crystal model system,
      which forms biaxial nematic liquid crystals, as functions of the density, from
      the Green-Kubo relations by equilibrium molecular dynamics simulation and by a
      nonequilibrium molecular dynamics algorithm, where a torque conjugate to the
      director angular velocity is applied to rotate the director. The model system
      consists of a soft ellipsoid-string fluid where the ellipsoids interact according
      a repulsive version of the Gay-Berne potential. Four different length-to-width-to
      breadth ratios have been studied. On compression, this system forms discotic or
      calamitic uniaxial nematic phases depending on the dimensions of the molecules,
      and on further compression a biaxial nematic phase is formed. In the uniaxial
      nematic phase there is one twist viscosity and one alignment angle. In the
      biaxial nematic phase there are three twist viscosities and three alignment
      angles corresponding to the rotation around the various directors and the
      different alignments of the directors relative to the stream lines, respectively.
      It is found that the smallest twist viscosity arises by rotation around the
      director formed by the long axes, the second smallest one arises by rotation
      around the director formed by the normals of the broadsides, and the largest one
      by rotation around the remaining director. The first twist viscosity is rather
      independent of the density whereas the last two ones increase strongly with
      density. One finds that there is one stable director alignment relative to the
      streamlines, namely where the director formed by the long axes is almost parallel
      to the stream lines and where the director formed by the normals of the
      broadsides is almost parallel to the shear plane. The relative magnitudes of the
      components of the twist viscosities span a fairly wide interval so this model
      should be useful for parameterisation experimental data.

PMID- 22847337
TI  - Seasonal variation of pharmaceutically active compounds in surface (Tagus River)
      and tap water (Central Spain).
AB  - Numerous studies have shown the presence of pharmaceutically active compounds
      (PhACs) in different environmental compartments, for example, in surface water or
      wastewater ranging from nanograms per litre to micrograms per litre. Likewise,
      some recent studies have pointed to seasonal variability, thus indicating that
      PhAcs concentrations in the aquatic environment may depend on the time of year.
      This work intended to find out (1) whether Tagus fluvial and drinking water were
      polluted with different groups of PhACs and (2) if their concentrations differed
      between winter and summer seasons. From the 58 substances analysed, 41 were found
      belonging to the main therapeutic groups. Statistical differences were seen for
      antibacterials, antidepressants, anxiolytics, antiepileptics, and cardiovascular
      drugs, with higher concentrations being detected in winter than in summer. These
      results might indicate that the PhACs analysed in this study undergo lower
      environmental degradation in winter than in summer. In order to confirm these
      initial results, a continuous monitoring should be performed especially on those
      PhACs that either because of an elevated consumption or an intrinsic chemical
      persistence are poorly degraded during winter months due to low temperatures and
      solar irradiation. It is especially important to identify which of these specific
      PhACs are in order to recommend their substitution by equally effective and safe
      substances but also environmentally friendly.

PMID- 22847340
TI  - Understanding Food and Drug Administration regulatory requirements for an
      investigational device exemption for sponsor-investigators.
AB  - Clinical investigators in academic medical centers often perceive federal
      regulations as a significant obstacle to conducting clinical research. The
      regulatory authority of the Food and Drug Administration (FDA) extends to
      clinical studies of medical devices. Consequently, researchers wishing to conduct
      device research using FDA-approved as well as nonapproved devices must comply
      with federal regulations for investigational device exemptions (IDE) as described
      in Title 21 of the Code of Federal Regulations Part 812. FDA regulatory oversight
      is structured to match the risk to the subject to the risk of the device. Medical
      device studies can be categorized as follows: meeting exemption criteria, being a
      nonsignificant risk device, or being a significant risk device. All IDE studies
      must meet regulations for the protection of human subjects, but no additional
      federal filing on the part of the investigator is necessary for those that meet
      exempt criteria. Nonsignificant risk device studies require meeting abbreviated
      IDE regulatory requirements for the conduct of the study, but no previous FDA
      approval is required. Significant risk device studies require that the
      investigator also function as a sponsor and to file an IDE with the FDA for
      approval before starting. A sponsor-investigator filing an IDE follows the format
      and content described in 21 CFR 812.20. The study may begin 30 days after the
      date of submission receipt unless the FDA notifies the sponsor otherwise. While
      the IDE is active, the sponsor-investigator must meet the requirements for the
      conduct of the study and the required monitoring and reporting to the FDA.

PMID- 22847341
TI  - Treatment of malignant gastric outlet obstruction with metallic stents: 
      assessment of whether gastrointestinal position alters efficacy.
AB  - OBJECTIVES: Gastric outlet obstruction (GOO) is a late complication of advanced
      gastric, pancreatic, and duodenal cancer. Palliative treatment of the obstruction
      is the main aim of therapy for these patients. Self-expandable metal stents are
      used for treating GOO. From our experience, the placement of the stent across the
      pylorus is easier and makes the curve of stent better than when the stent is
      placed within the duodenal area. The purposes of this study were to assess the
      efficacy of stents placed in either the duodenal area or across the pyloric valve
      in relieving GOO symptoms and to evaluate whether the location of the stent
      affects treatment outcomes. MATERIALS AND METHODS: This was a retrospective
      single-site study of 44 patients with malignant GOO. Expanding metal stents were
      placed either across the pyloric valve (n = 22; group A) or in the duodenum area
      (n = 22; group B). Improvement in oral intake was monitored using the Gastric
      Outlet Obstruction Scoring System (GOOSS). The end of the study was death of the
      last enrolled patient or 6 months after enrollment of the last patient, or
      whatever came first. RESULTS: Stent implantation similarly improved the patients'
      tolerance for food intake from baseline for both groups A and B (median
      [interquartile range]; 2 [2-3] and 2 [2-3], respectively). Patients in group B
      who received adjunctive chemotherapy had greater improvement in GOOSS and
      survival than patients in group B who did not have chemotherapy or any group A
      patients (P < 0.05). Stent patency was not affected by stent position or
      chemotherapy. CONCLUSION: Palliative treatment of GOO with placement of an
      expandable metal stent improved the tolerability of food intake. The location of
      stent across the pyloric valve or within the duodenum did not affect the efficacy
      of the procedure or stent patency.

PMID- 22847342
TI  - Insulin resistance predicts steatosis and fibrosis in morbidly obese patients
      undergoing bariatric surgery.
AB  - BACKGROUND: Influence of adipokines and insulin resistance on liver histology is
      an unclear area in morbidly obese patients. OBJECTIVE: The aim of our study was
      to study the influence of insulin resistance and adipokines in the grade of liver
      steatosis and fibrosis in morbidly obese patients undergoing bariatric surgery.
      SETTING: Tertiary hospital. MATERIALS AND METHODS: A sample of 36 morbidly obese
      patients undergoing bariatric surgery was analyzed in a cross-sectional study. A
      liver biopsy was performed. Weights, basal glucose, insulin, insulin resistance
      (homeostasis model assessment for insulin resistance [HOMA-IR]), total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglycerides, and adipokine blood levels were measured. RESULTS:
      Seventeen patients (47.2%) had low-grade steatosis, and 19 patients (52.8%) had
      high-grade steatosis. Sixteen patients (44.4%) did not have liver fibrosis, and
      20 patients (56.6%) had liver fibrosis. Only insulin levels, HOMA-IR, and
      aspartate aminotransferase activity were higher in the patients with high-grade
      steatosis. Insulin levels and HOMA-IR were higher in patients with fibrosis. In
      the logistic regression analysis with a dependent dichotomous variable (grades of
      steatosis: low vs high), the HOMA-IR remained in the model, with an odds ratio to
      develop high-grade steatosis of 1.33 (95% confidence interval, 1.09-1.86). In the
      second logistic regression analysis with a dependent dichotomy variable (grades
      of fibrosis: present vs absent), the HOMA-IR remained in the model, with an odds
      ratio to develop fibrosis of 1.53 (95% confidence interval, 1.13-2.51).
      CONCLUSION: Insulin resistance determined with HOMA-IR model is associated with
      high-grade steatosis and liver fibrosis in obese patients before bariatric
      surgery.

PMID- 22847343
TI  - Influence of renal artery variants, number, location, and degree of renal artery
      stenoses on the atherosclerotic burden of the aorta.
AB  - OBJECTIVE: To determine the assumed influence of the number of renal arteries,
      the distribution and extent of renal artery stenosis (RAS), and the kidney length
      on calcified aortic atherosclerotic plaque burden. METHODS: The computed
      tomographic angiographies of 1381 patients were analyzed retrospectively using a
      volumetric aortic calcium scoring method. The Spearman method was used to
      calculate the correlation between kidney length, number and diameter of renal
      arteries, as well as number, degree, and location of RASs on main or additional
      renal arteries with the extent of aortic atherosclerosis. Logistic regression
      analyses were conducted with the target variable "calcification present or
      absent." RESULTS: Patients with multiple renal arteries (38.3%) had lower plaque
      volumes than patients without such variants (0.55 +/- 0.97 vs 0.64 +/- 1.06 mL; P
      < 0.05). Renal artery stenoses affected all renal vessels with equal frequency.
      The aortic calcium score correlated with the number of RASs (P < 0.0001) and the
      maximum degree of RAS up to a threshold of 60%. Location of an RAS in the various
      renal arteries was irrelevant. In regression analyses, the presence of RAS (Wald
      = 5.523), the degree of RAS (Wald = 6.251), and age (Wald = 223.1) were positive
      predictors of the aortic calcium score, whereas kidney length (Wald = 9.564)
      proved to be a negative predictor. CONCLUSION: The aortic calcium score
      correlates with both the number of RASs and the maximum degree of RAS up to a
      threshold of 60% but correlates inversely with the number of renal arteries.
      Renal artery stenosis affects all renal vessels with equal frequency, and this
      finding should be considered in screening procedures.

PMID- 22847344
TI  - Final results of a randomized trial comparing 1, 3, or 6 infusions of Rituximab
      plus 6 cycles CHOP provide valuable preliminary data towards a more cost
      effective and safer treatment of advanced follicular lymphoma.

PMID- 22847345
TI  - Dialysis: Choice of dialysis--what to do with economic incentives.
AB  - A survey of seven countries has found a striking difference in dialysis
      reimbursement policies, even when data were adjusted for gross domestic product
      per capita. Although increased reimbursement is perceived to be a valuable
      incentive for certain treatments, this perception is not supported by current
      data and alternative strategies to promote home-based dialysis should be pursued.

PMID- 22847350
TI  - A comparative analysis of proteins that accumulate during the initial stage of
      root hair development in barley root hair mutants and their parent varieties.
AB  - The mechanisms of root hair formation have been studied extensively in
      Arabidopsis but knowledge about these processes in monocot species is still
      limited, especially in relation to the proteome level. The aim of this study was
      to identify the proteins that are involved in the initiation and the early stage
      of root hair tip growth in barley using two-dimensional (2D) electrophoresis and
      mass spectrometry. A comparison of proteins that accumulate differentially in two
      root hair mutants and their respective parent varieties resulted in the
      identification of 13 proteins that take part in several processes related to the
      root hair morphogenesis, such as the control of vesicular trafficking, ROS
      signalling and homeostasis, signal transduction by phospholipids metabolism and
      ATP synthesis. Among the identified proteins, two ATP synthases, two ABC
      transporters, a small GTPase from the SAR1 family, a PDI-like protein, a
      monodehydroascorbate reductase, a C2 domain-containing protein and a Wali7 domain
      containing protein were found. This study is the first report on the proteins
      identified in the initial stage of root hair formation in barley and gives new
      insights into the mechanisms of root hair morphogenesis in a monocot species.

PMID- 22847360
TI  - Production and separation of dipeptidyl peptidase IV from Lactococcus lactis:
      scale up for industrial production.
AB  - Lactococcus lactis spp. lactis and Lactococcus lactis spp. cremoris are widely
      used in the manufacture of fermented milk. These strains were compared for
      production of Dipeptidyl Peptidase IV (DPP IV) enzyme in terms of enzyme
      activity, specific growth rates and productivity. Lactococcus lactis spp. lactis
      was produced in 3 L bioreactor and scaled up to 30 and 150 L stirred tank
      bioreactors, and the enzyme activities were found as 110, 110 and 122 mU mL(-1),
      respectively. After 8 h of production, separation steps were performed. While
      purification fold was 127 and yield was 2.69 %, the molecular weight of the
      enzyme was estimated as 68 kDa. Partially purified enzyme was enteric coated with
      capsules and a 95.5 % of DPP IV enzyme passed into the artificial intestine.
      Results show that production of DPP IV enzyme by Lactococcus lactis spp. lactis
      strain in submerged culture is comparable with the productions by commercial
      strains, mostly Aspergillus, in solid state fermentations based on productivity.

PMID- 22847359
TI  - Battery explantation after sacral neuromodulation in the Medicare population.
AB  - AIMS: To determine sacral neuromodulation battery life and the patient and
      provider risk factors for early explantation in a population-based sample.
      METHODS: A 5% sample of Medicare beneficiaries from 1997 to 2007 served as the
      data source. All patients who had a sacral neuromodulation device implanted in
      that time period were included. Variables included in a multivariate analysis of
      risk factors for removal included gender, age, race, diagnosis, type of test
      phase, provider specialty, and volume. The number of device reprogramming events
      was also recorded in this time period. RESULTS: Mean follow-up was 60.5 months.
      Patients on average had 2.15 reprogramming episodes in their first year, with
      that number decreasing over subsequent years. Out of the 558 batteries implanted
      63 (11.3%) were explanted. Of the 19 implanted individuals who carried the
      diagnosis of interstitial cystitis (IC), 11 (57.9%) had the battery removed. This
      was the only variable that predicted early removal, with an odds ratio of
      explantation of 10.5 (95% CI: 3.9-28.4). CONCLUSION: Very few sacral
      neuromodulation batteries, once implanted, are removed prematurely. Patients with
      IC, however, are at very high risk of requiring premature battery removal.

PMID- 22847361
TI  - Multi-objective optimal control of dynamic bioprocesses using ACADO Toolkit.
AB  - The optimal design and operation of dynamic bioprocesses gives in practice often
      rise to optimisation problems with multiple and conflicting objectives. As a
      result typically not a single optimal solution but a set of Pareto optimal
      solutions exist. From this set of Pareto optimal solutions, one has to be chosen
      by the decision maker. Hence, efficient approaches are required for a fast and
      accurate generation of the Pareto set such that the decision maker can easily and
      systematically evaluate optimal alternatives. In the current paper the multi
      objective optimisation of several dynamic bioprocess examples is performed using
      the freely available ACADO Multi-Objective Toolkit ( http://www.acadotoolkit.org
      ). This toolkit integrates efficient multiple objective scalarisation strategies
      (e.g., Normal Boundary Intersection and (Enhanced) Normalised Normal Constraint)
      with fast deterministic approaches for dynamic optimisation (e.g., single and
      multiple shooting). It has been found that the toolkit is able to efficiently and
      accurately produce the Pareto sets for all bioprocess examples. The resulting
      Pareto sets are added as supplementary material to this paper.

PMID- 22847362
TI  - Irradiance optimization of outdoor microalgal cultures using solar tracked
      photobioreactors.
AB  - Photosynthetic activity and temperature regulation of microalgal cultures
      (Chlorella vulgaris and Scenedesmus obliquus) under different irradiances
      controlled by a solar tracker and different cell densities were studied in
      outdoor flat panel photobioreactors. An automated process control unit regulated
      light and temperature as well as pH value and nutrient concentration in the
      culture medium. CO2 was supplied using flue gas from an attached combined block
      heat and power station. Photosynthetic activity was determined by pulse amplitude
      modulation fluorometry. Compared to the horizontal irradiance of 55 mol photons
      m(-2) d(-1) on a clear day, the solar tracked photobioreactors enabled a decrease
      and increase in the overall light absorption from 19 mol photons m(-2) d(-1) (by
      rotation out of direct irradiance) to 79 mol photons m(-2) d(-1) (following the
      position of the sun). At biomass concentrations below 1.1 g cell dry weight (CDW)
      L(-1), photoinhibition of about 35 % occurred at irradiances of >=1,000 MUmol
      photons m(-2) s(-1) photosynthetic active radiation (PAR). Using solar tracked
      photobioreactors, photoinhibition can be reduced and at optimum biomass
      concentration (>=2.3 g CDW L(-1)), the culture was irradiated up to 2,000 MUmol
      photons m(-2) s(-1) to overcome light limitation with biomass yields of 0.7 g CDW
      mol photons(-1) and high photosynthetic activities indicated by an effective
      quantum yield of 0.68 and a maximum quantum yield of 0.80 (F v/F m). Overheating
      due to high irradiance was avoided by turning the PBR out of the sun or using a
      cooling system, which maintained the temperature close to the species-specific
      temperature optima.

PMID- 22847363
TI  - A simple and efficient DNA isolation method for Salvia officinalis.
AB  - We report an efficient, simple, and cost-effective protocol for the isolation of
      genomic DNA from an aromatic medicinal plant, common sage (Salvia officinalis
      L.). Our modification of the standard CTAB protocol includes two polyphenol
      adsorbents (PVP 10 and activated charcoal), high NaCl concentrations (4 M) for
      removing polysaccharides, and repeated Sevag treatment to remove proteins and
      other carbohydrate contaminants. The mean DNA yield obtained with our Protocol 2
      was 330.6 MUg DNA g(-1) of dry leaf tissue, and the absorbance ratios 260/280 and
      260/230 nm averaged 1.909 and 1.894, respectively, revealing lack of
      contamination. PCR amplifications of one nuclear (26S rDNA) and one chloroplast
      (rps16-trnK) locus indicated that our DNA isolation protocol may be used in
      common sage and other aromatic and medicinal plants containing essential oil for
      molecular biologic and biotechnological studies and for population genetics,
      phylogeographic, and conservation surveys in which nuclear or chloroplast genomes
      would be studied in large numbers of individuals.

PMID- 22847364
TI  - Villous papillary thyroid carcinoma: a variant associated with marfan syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant hereditary disorder of connective
      tissue associated with perturbations in transforming growth factor beta (TGF
      beta) biology, most often due to mutations in FBN1 gene that encodes fibrillin-1.
      To our knowledge, there is no known association of MFS with thyroid carcinoma. We
      report a 46-year-old man with known history of MFS who developed an unusual
      histological variant of papillary thyroid carcinoma. The tumor exhibited a widely
      invasive florid papillary growth pattern with prominent long villous fronds.
      Immunohistochemical and molecular analysis revealed a BRAF(V600E) mutation,
      evidence of aggressive biomarker expression (positivity for HBME-1, cytokeratin
      19, galectin-3 and cyclin D1, and loss of p27), and changes associated with TGF
      beta-related epithelial-to-mesenchymal transition with active phospho-SMAD
      signaling. We introduce a unique histological pattern of papillary thyroid
      carcinoma that is associated with MFS. The combination of BRAF(V600E) mutation in
      the setting of altered TGF-beta signaling and weak connective tissue integrity
      associated with MFS may cooperate and possibly be responsible to form this unique
      villous morphology with epithelial-to-mesenchymal transition and invasive growth.

PMID- 22847365
TI  - Cardiac involvement in adult polymyositis or dermatomyositis: a systematic
      review.
AB  - BACKGROUND: To investigate the clinical features of cardiac involvement in
      polymyositis (PM) or dermatomyositis (DM). HYPOTHESIS: More attention will be
      focused on the heart in PM/DM as we would have wished, which contribute to
      improve the prognosis. METHODS: All articles published in English were retrieved
      by searching MEDLINE via PubMed (1975-2011). After selecting eligible articles
      according to the predefined inclusion and exclusion criteria, a systemic review
      was carried out. RESULTS: A total of 26 articles were included in this study,
      which included 1530 patients. The incidence of cardiac involvement was 9% to 72%.
      Heart failure was the most frequent (32% to 77%) clinical symptom. Among the
      abnormal electrocardiogram and ultrasonic cardiogram, the incidence of conduction
      abnormalities, left ventricular diastolic dysfunction, and hyperkinetic left
      ventricular contraction were 25% to 38.5%, 42%, and 6% to 12%, respectively. The
      pathologic findings revealed myocardial inflammation, degenerative changes and
      necrosis similar to that in skeletal muscles. Cardiac manifestations of some
      patients improved after glucocorticoid and immunosuppressant treatment. Thirty
      seven patients (46.3%) died as a direct result of heart disease. CONCLUSIONS:
      Heart abnormalities are frequent in patients with PM/DM, most of which were
      subclinical. The efficacy of glucocorticoids and immunosuppressants is uncertain.
      Cardiac involvement is a common cause of death.

PMID- 22847368
TI  - 'One-pot' Hammett plots: a general method for the rapid acquisition of relative
      rate data.
AB  - A general 'one-pot' method for determining relative rates of reaction in complex
      mixtures has been established using free energy relationships to demonstrate its
      utility. Competition experiments involving as many as seven species gave relative
      rate constants that are in good agreement to those obtained from individual
      kinetic analyses.

PMID- 22847366
TI  - Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus
      nephritis from 2000 to 2004 among children in the US Medicaid beneficiary
      population.
AB  - OBJECTIVE: To investigate the nationwide prevalence, incidence, and
      sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among
      children in the US Medicaid beneficiary population. METHODS: Children ages 3
      years to <18 years with a diagnosis of SLE (defined as >=3 claims with an
      International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0
      for SLE, each >30 days apart) were identified from the US Medicaid Analytic
      eXtract database from 2000 to 2004. This database contains all inpatient and
      outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus
      nephritis was identified from >=2 ICD-9 billing codes for glomerulonephritis,
      proteinuria, or renal failure, each recorded >30 days apart. The prevalence and
      incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled
      children overall and within sociodemographic groups. RESULTS: Of the 30,420,597
      Medicaid-enrolled children during these years, 2,959 were identified as having
      SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08)
      per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were
      female, 40% were African American, 25% were Hispanic, 21% were White, and 42%
      resided in the South region of the US. Moreover, of the children with SLE, 1,106
      (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86)
      per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI
      2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per
      100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE
      and lupus nephritis increased with age, were higher in girls than in boys, and
      were higher in all non-White racial/ethnic groups. CONCLUSION: In the current
      study, the prevalence and incidence rates of SLE among Medicaid-enrolled children
      in the US are high compared to studies in other populations. In addition, these
      data represent the first population-based estimates of the prevalence and
      incidence of lupus nephritis in the US to date.

PMID- 22847369
TI  - Designing benzosiloles for better optoelectronic properties using DFT & TDDFT
      approaches.
AB  - Like siloles, benzosiloles have low lying LUMOs due to sigma*-pi* conjugation
      between Si and the butadiene moiety but are more amenable for structural tuning.
      In total, 27 benzosiloles, 12 of them already synthesized and another 15 newly
      reported here, have been investigated using DFT and TDDFT calculations with an
      aim to check their suitability for optoelectronic applications. Our results show
      that all these molecules have excellent pi-conjugation throughout. Frontier
      molecular orbital analysis gives an estimate of the band gap of these benzosilole
      derivatives and further reveals that the LUMOs are highly localized on the
      benzosilole moiety whereas HOMOs are localized on both the benzosilole moiety and
      the substituents. TDDFT calculations have been performed to understand the
      absorption properties in gas and solvent phases. PCM calculations show that
      solvation has a minimum effect on absorption maxima. Among the different
      functionals, PBE0 was found to perform well compared to other functionals and the
      computed absorption spectra are in good agreement with experiments. Among the
      designed candidates, styryl substituted benzosiloles are the most promising,
      showing higher wavelength of absorption and would make better OLED materials. NBO
      and AIM analysis provide evidence for complete delocalization in these systems.
      It is interesting to note that eleven out of the fifteen newly designed
      candidates have lower band gaps than the best known benzosilole derivatives
      synthesized so far.

PMID- 22847370
TI  - Selectivity of arsenite interaction with zinc finger proteins.
AB  - Arsenic is a carcinogenic element also used for the treatment of acute
      promyelocytic leukemia. The reactivity of proteins to arsenic must be associated
      with the various biological functions of As. Here, we investigated the
      selectivity of arsenite to zinc finger proteins (ZFPs) with different zinc
      binding motifs (C2H2, C3H, and C4). Single ZFP domain proteins were used for the
      direct comparison of the reactivity of different ZFPs. The binding constants and
      the reaction rates have been studied quantitatively. Results show that both the
      binding affinity and reaction rates of single-domain ZFPs follow the trend of C4
      > C3H ? C2H2. Compared with the C2H2 motif ZFPs, the binding affinities of C3H
      and C4 motif ZFPs are nearly two orders of magnitude higher and the reaction
      rates are approximately two-fold higher. The formation of multi-domain ZFPs
      significantly enhances the reactivity of C2H2 type ZFPs, but has negligible
      effects on C3H and C4 ZFPs. Consequently, the reactivities of the three types of
      multi-domain ZFPs are rather similar. The 2D NMR spectra indicate that the
      As(III)-bound ZFPs are also unfolded, suggesting that arsenic binding interferes
      with the function of ZFPs.

PMID- 22847371
TI  - Effects of EG-VEGF, VEGF and TGF-beta1 on pregnancy outcome in patients
      undergoing IVF-ET treatment.
AB  - PURPOSE: To investigate the correlation of endocrine gland-derived vascular
      endothelial growth factor (EG-VEGF), vascular endothelial growth factor (VEGF)
      and transforming growth factor beta 1 (TGF-beta1) with the corresponding
      reproductive outcome in patients who received in vitro fertilization-embryo
      transfer (IVF-ET). METHODS: Sixty-seven women undergoing IVF-ET at a university
      tertiary hospital were recruited for a prospective study. Concentrations of EG
      VEGF, VEGF and TGF-beta1 were measured by enzyme-linked immunosorbent assay
      (ELISA) in follicular fluid (FF) collected during oocyte retrieval (OR) and in
      serum collected 2 days after OR. RESULTS: In FF, concentrations of both EG-VEGF
      and VEGF were negatively correlated with peak E2 and the number of MII oocytes
      retrieved, and positively correlated with each other. In serum, concentrations of
      all the three growth factors were positively correlated with the rate of good
      quality embryo, and with one another. Patients in the pregnancy group had lower
      peak E2 concentrations and higher serum EG-VEGF concentrations than those in the
      non-pregnancy group, but such tendency was not observed in the case of VEGF and
      TGF-beta1. CONCLUSIONS: Both concentrations of EG-VEGF and VEGF in FF were
      negatively correlated with ovarian response and oocyte maturation. Concentrations
      of all the three growth factors in serum were positively correlated with embryo
      quality, but only serum concentrations of EG-VEGF were associated with the
      pregnancy outcome.

PMID- 22847372
TI  - Day 5 expanded blastocysts transferred on same day have comparable outcome to
      those left for more extended culture and transferred on day 6.
AB  - OBJECTIVE: To study the outcome of blastocysts showing expansion on day 5 and
      transferred on day 5 or 6, in comparison with those unexpanded and transferred on
      day 6. STUDY DESIGN: Prospective cohort of 221 women prepared for BET classified
      into three groups according to timing of blastocyst expansion and day of embryo
      transfer. Group I; with expanded blastocysts on day 5 having day 5 transfer,
      group II; with expanded blastocysts on day 5 having day 6 transfer and group III
      ; with delayed expansion undergoing day 6 BET. RESULTS: Implantation rates,
      pregnancy rates, ongoing pregnancy rates, and live birth rates in the first 2
      groups were almost double the rates in the third group. The figures for
      implantation rates were 40 % in the first two groups vs. 19 % in the third group
      (P < 0.05). Pregnancy rates were 60.9 % and 64 % vs. 31.8 % (P < 0.05) and
      ongoing pregnancy/ live-birth rates were 52.3 % & 56 % vs. 27.3 %. CONCLUSION:
      The current study reports better implantation and pregnancy rates with earlier
      expanding blastocysts regardless of the time of transfer.

PMID- 22847373
TI  - Rapid antidepressant effect of ketamine in the electroconvulsive therapy setting.
AB  - OBJECTIVES: Studies now provide strong evidence that the N-methyl-D-aspartate
      receptor antagonist ketamine possesses rapidly acting antidepressant properties.
      This study aimed to determine if a low dose of ketamine could be used to expedite
      and augment the antidepressant effects of electroconvulsive therapy (ECT)
      treatments in patients experiencing a severe depressive episode. MATERIALS AND
      METHODS: Subjects with major depressive disorder or bipolar disorder referred for
      ECT treatment of a major depressive episode were randomized to receive thiopental
      alone or thiopental plus ketamine (0.5 mg/kg) for anesthesia before each ECT
      session. The Hamilton Depression Rating Scale (HDRS) was administered at baseline
      and at 24 to 72 hours after the first and sixth ECT sessions. RESULTS:
      Electroconvulsive therapy exerted a significant antidepressant effect in both
      groups (F2,24 = 14.35, P < 0.001). However, there was no significant group effect
      or group-by-time interaction on HDRS scores. In addition, post hoc analyses of
      the time effect on HDRS showed no significant HDRS reduction after the first ECT
      session for either group. CONCLUSIONS: The results of this pilot study suggest
      that ketamine, at a dose of 0.5 mg/kg, given just before ECT, did not enhance the
      antidepressant effect of ECT. Interestingly, the results further suggest that the
      coadministration of ketamine with a barbiturate anesthetic and ECT may attenuate
      the immediate antidepressant effects of the N-methyl-D-aspartate antagonist.

PMID- 22847374
TI  - eMouseAtlas, EMAGE, and the spatial dimension of the transcriptome.
AB  - eMouseAtlas (www.emouseatlas.org) is a comprehensive online resource to visualise
      mouse development and investigate gene expression in the mouse embryo. We have
      recently deployed a completely redesigned Mouse Anatomy Atlas website
      (www.emouseatlas.org/emap/ema) that allows users to view 3D embryo
      reconstructions, delineated anatomy, and high-resolution histological sections. A
      new feature of the website is the IIP3D web tool that allows a user to view
      arbitrary sections of 3D embryo reconstructions using a web browser. This feature
      provides interactive access to very high-volume 3D images via a tiled pan-and
      zoom style interface and circumvents the need to download large image files for
      visualisation. eMouseAtlas additionally includes EMAGE (Edinburgh Mouse Atlas of
      Gene Expression) (www.emouseatlas.org/emage), a freely available, curated online
      database of in situ gene expression patterns, where gene expression domains
      extracted from raw data images are spatially mapped into atlas embryo models. In
      this way, EMAGE introduces a spatial dimension to transcriptome data and allows
      exploration of the spatial similarity between gene expression patterns. New
      features of the EMAGE interface allow complex queries to be built, and users can
      view and compare multiple gene expression patterns. EMAGE now includes mapping of
      3D gene expression domains captured using the imaging technique optical
      projection tomography. 3D mapping uses WlzWarp, an open-source software tool
      developed by eMouseAtlas.

PMID- 22847375
TI  - BioGPS and GXD: mouse gene expression data-the benefits and challenges of data
      integration.
AB  - Mouse gene expression data are complex and voluminous. To maximize the utility of
      these data, they must be made readily accessible through databases, and those
      resources need to place the expression data in the larger biological context.
      Here we describe two community resources that approach these problems in
      different but complementary ways: BioGPS and the Mouse Gene Expression Database
      (GXD). BioGPS connects its large and homogeneous microarray gene expression
      reference data sets via plugins with a heterogeneous collection of external gene
      centric resources, thus casting a wide but loose net. GXD acquires different
      types of expression data from many sources and integrates these data tightly with
      other types of data in the Mouse Genome Informatics (MGI) resource, with a strong
      emphasis on consistency checks and manual curation. We describe and contrast the
      "loose" and "tight" data integration strategies employed by BioGPS and GXD,
      respectively, and discuss the challenges and benefits of data integration. BioGPS
      is freely available at http://biogps.org . GXD is freely available through the
      MGI web site ( www.informatics.jax.org ) or directly at
      www.informatics.jax.org/expression.shtml .

PMID- 22847376
TI  - Association studies in outbred mice in a new era of full-genome sequencing.
AB  - Thousands of loci that contribute to quantitative traits in outbred crosses of
      mice have been reported over the last two decades. In this review we discuss how
      outbred mouse populations can be used to map and identify the genes and sequence
      variants that give rise to quantitative variation. We discuss heterogeneous
      stocks, the diversity outbred, and commercially available outbred populations of
      mice. All of these populations are descended from a small number of progenitor
      strains. The availability of the complete sequence of laboratory strains means
      that in many cases it will be possible to reconstruct the genomes of the outbred
      animals so that in a genetic association study we can detect the effect of all
      variants, a situation that has so far eluded studies in completely outbred
      populations. These resources constitute a major advance and make it possible to
      progress from a quantitative trait locus to a gene at an unprecedented speed.

PMID- 22847377
TI  - Status and access to the Collaborative Cross population.
AB  - The Collaborative Cross (CC) is a panel of recombinant inbred lines derived from
      eight genetically diverse laboratory inbred strains. Recently, the genetic
      architecture of the CC population was reported based on the genotype of a single
      male per line, and other publications reported incompletely inbred CC mice that
      have been used to map a variety of traits. The three breeding sites, in the US,
      Israel, and Australia, are actively collaborating to accelerate the inbreeding
      process through marker-assisted inbreeding and to expedite community access of CC
      lines deemed to have reached defined thresholds of inbreeding. Plans are now
      being developed to provide access to this novel genetic reference population
      through distribution centers. Here we provide a description of the distribution
      efforts by the University of North Carolina Systems Genetics Core, Tel Aviv
      University, Israel and the University of Western Australia.

PMID- 22847378
TI  - Four new myrsinol diterpenes from Euphorbia prolifera.
AB  - Four new myrsinol diterpenes, euphorbialoids K-N (1-4), have been isolated from
      the roots of Euphorbia prolifera. Their structures were elucidated on the basis
      of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESI-MS and HR
      ESI-MS) spectroscopic data analyses.

PMID- 22847379
TI  - New glycosides of acetophenone derivatives and phenylpropanoids from Juniperus
      occidentalis.
AB  - New glycosides of seven acetophenone derivatives (1-7) and two phenylpropanoids
      (8, 9), named juniperosides III-XI, have been isolated from the MeOH extract of
      the leaves and stems of Juniperus occidentalis Hook. (Cupressaceae), together
      with eleven other known compounds. The structures of these compounds have been
      successfully elucidated using a variety of spectroscopic techniques.

PMID- 22847380
TI  - Effect of phenylalanine on Taxol production and antioxidant activity of extracts
      of suspension-cultured hazel (Corylus avellana L.) cells.
AB  - Taxol is produced by a few microorganisms and plants such as yew (Taxus sp.).
      Recent researches have shown that hazel (Corylus avellana L.) is also able to
      produce Taxol. In the present study, effects of different concentrations of
      phenylalanine (Phe) on the production of Taxol, antioxidant activity, and
      cytotoxic effects of extracts of suspension-cultured hazel cells were
      investigated. The cells were treated with different concentrations of Phe on day
      7 of subculture and were harvested on day 14. The results showed that the amounts
      of Taxol and antioxidant activity were increased by increasing the phenylalanine
      supply. Interestingly, the cytotoxic effects of hazel cell extract were even
      stronger than that of pure Taxol (standard), suggesting hazel cell extract as a
      novel and suitable probe for treating human cancer. Application of phenylalanine
      to hazel cells exaggerates their effects.

PMID- 22847382
TI  - A haemorrhagic, contrast-enhancing lesion of the basal ganglia.

PMID- 22847384
TI  - Stroke: Expanded indications for stroke thrombolysis--what next?

PMID- 22847383
TI  - Associations of insulin-like growth factor and insulin-like growth factor binding
      protein-3 with mortality in women with breast cancer.
AB  - Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial
      cell mitogen, is associated with breast cancer development. However, its
      association with breast cancer survival is not established. Circulating
      concentrations of IGF-1 are controlled via binding proteins, including IGF
      Binding Protein-3 (IGFBP-3), that may modulate the association of IGF-1 with
      breast-cancer outcomes. We measured IGF-1 and IGFBP-3 concentrations in serum
      from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL)
      study, a multiethnic, prospective cohort study of women diagnosed with stage I
      IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and
      as a ratio, modeled using quintile cut-points, with risk of breast cancer
      specific (n = 42 deaths) and all-cause mortality (n = 87 deaths) using Cox
      proportional hazards models. In models adjusted for body mass index, ethnicity,
      tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP-3,
      women in the highest quintile of IGF-1 level had an increased risk of all-cause
      mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21-7.93, p = 0.02), although no
      dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of
      free IGF-I levels, was significantly associated with increasing risk of all-cause
      mortality (HR = 2.83, 95% CI 1.25-6.36 p(trend)  = 0.01, upper vs. lower
      quintile) in a fully adjusted model. In conclusion, high serum levels of IGF-1
      and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause
      mortality in women with breast cancer. These results need to be confirmed in
      larger breast cancer survivor cohorts.

PMID- 22847385
TI  - Whole-genome and whole-exome sequencing in neurological diseases.
AB  - Genetic risk factors that underlie many rare and common neurological disorders
      remain poorly understood because of the multifactorial and heterogeneous nature
      of these complex traits. With the decreasing cost of massively parallel
      sequencing technologies, whole-genome and whole-exome sequencing will soon allow
      the characterization of the full spectrum of sequence and structural variants
      present in each individual. Methods are being developed to parse the huge amount
      of genomic data and to sift out which variants are associated with diseases.
      Numerous challenges are inherent in the identification of rare and common
      variants that have a role in complex neurological diseases, and tools are being
      developed to overcome these challenges. Given that genomic data will soon be the
      main driver towards the goal of personalized medicine, future developments in the
      production and interpretation of data, as well as in ethics and counselling, will
      be needed for whole-genome and whole-exome sequencing to be used as informative
      tools in a clinical setting.

PMID- 22847387
TI  - Response to Vermorken et al--curcumin and free light chains.

PMID- 22847386
TI  - Hyponatremia may reflect severe inflammation in children with febrile urinary
      tract infection.
AB  - BACKGROUND: Hyponatremia is the most common electrolyte abnormality in clinical
      practice, but little is known about the association between febrile urinary tract
      infection (UTI) and hyponatremia or its significance to clinical outcomes.
      METHODS: Data from 140 children with febrile UTI between 2000 and 2010 were
      retrospectively analyzed. Laboratory examinations [white blood cell (WBC) count,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum sodium
      concentration], renal ultrasonography, (99m)Technetium-dimercaptosuccinic acid
      (DMSA) scintigraphy, and voiding cystourethrogram were performed. Culture growing
      >50,000 colonies of one single bacterial species on a urine sample obtained by
      catheter or >100,000 colonies on two clean-catch samples was required to
      establish diagnosis of UTI. RESULTS: In children with renal cortical defects
      diagnosed after DMSA scintigraphy (group 1), duration of fever was significantly
      longer (P = 0.038) and WBC (P = 0.047) and CRP (P < 0.0001) levels significantly
      higher than in those without renal cortical defects (group 2). However, serum
      sodium levels were significantly lower in group 1 than group 2 (135.9 +/- 2.4 vs
      137.4 +/- 2.7 mEq/L, P = 0.007). Hyponatremia (serum sodium <= 135 mEq/L) was
      also more frequent in group 1 than in group 2 (74.1 % vs 45.3 %, P = 0.012).
      Serum sodium concentration was negatively correlated with WBC count (r = -0.156,
      P = 0.011) and CRP levels (r = -0.160, P= 0.028). CONCLUSIONS: Our study
      indicates that hyponatremia may be a substantial inflammatory marker and is
      significantly and independently associated with the degree of inflammation in
      children with febrile UTI.

PMID- 22847388
TI  - A faster, high resolution, mtPA-GFP-based mitochondrial fusion assay acquiring
      kinetic data of multiple cells in parallel using confocal microscopy.
AB  - Mitochondrial fusion plays an essential role in mitochondrial calcium
      homeostasis, bioenergetics, autophagy and quality control. Fusion is quantified
      in living cells by photo-conversion of matrix targeted photoactivatable GFP
      (mtPAGFP) in a subset of mitochondria. The rate at which the photoconverted
      molecules equilibrate across the entire mitochondrial population is used as a
      measure of fusion activity. Thus far measurements were performed using a single
      cell time lapse approach, quantifying the equilibration in one cell over an hour.
      Here, we scale up and automate a previously published live cell method based on
      using mtPAGFP and a low concentration of TMRE (15 nm). This method involves
      photoactivating a small portion of the mitochondrial network, collecting highly
      resolved stacks of confocal sections every 15 min for 1 hour, and quantifying the
      change in signal intensity. Depending on several factors such as ease of finding
      PAGFP expressing cells, and the signal of the photoactivated regions, it is
      possible to collect around 10 cells within the 15 min intervals. This provides a
      significant improvement in the time efficiency of this assay while maintaining
      the highly resolved subcellular quantification as well as the kinetic parameters
      necessary to capture the detail of mitochondrial behavior in its native
      cytoarchitectural environment. Mitochondrial dynamics play a role in many
      cellular processes including respiration, calcium regulation, and apoptosis. The
      structure of the mitochondrial network affects the function of mitochondria, and
      the way they interact with the rest of the cell. Undergoing constant division and
      fusion, mitochondrial networks attain various shapes ranging from highly fused
      networks, to being more fragmented. Interestingly, Alzheimer's disease,
      Parkinson's disease, Charcot Marie Tooth 2A, and dominant optic atrophy have been
      correlated with altered mitochondrial morphology, namely fragmented networks.
      Often times, upon fragmentation, mitochondria become depolarized, and upon
      accumulation this leads to impaired cell function. Mitochondrial fission has been
      shown to signal a cell to progress toward apoptosis. It can also provide a
      mechanism by which to separate depolarized and inactive mitochondria to keep the
      bulk of the network robust. Fusion of mitochondria, on the other hand, leads to
      sharing of matrix proteins, solutes, mtDNA and the electrochemical gradient, and
      also seems to prevent progression to apoptosis. How fission and fusion of
      mitochondria affects cell homeostasis and ultimately the functioning of the
      organism needs further understanding, and therefore the continuous development
      and optimization of how to gather information on these phenomena is necessary.
      Existing mitochondrial fusion assays have revealed various insights into
      mitochondrial physiology, each having its own advantages. The hybrid PEG fusion
      assay, mixes two populations of differently labeled cells (mtRFP and mtYFP), and
      analyzes the amount of mixing and colocalization of fluorophores in fused,
      multinucleated, cells. Although this method has yielded valuable information, not
      all cell types can fuse, and the conditions under which fusion is stimulated
      involves the use of toxic drugs that likely affect the normal fusion process.
      More recently, a cell free technique has been devised, using isolated
      mitochondria to observe fusion events based on a luciferase assay. Two human cell
      lines are targeted with either the amino or a carboxy terminal part of Renilla
      luciferase along with a leucine zipper to ensure dimerization upon mixing.
      Mitochondria are isolated from each cell line, and fused. The fusion reaction can
      occur without the cytosol under physiological conditions in the presence of
      energy, appropriate temperature and inner mitochondrial membrane potential.
      Interestingly, the cytosol was found to modulate the extent of fusion,
      demonstrating that cell signaling regulates the fusion process. This assay will
      be very useful for high throughput screening to identify components of the fusion
      machinery and also pharmacological compounds that may affect mitochondrial
      dynamics. However, more detailed whole cell mitochondrial assays will be needed
      to complement this in vitro assay to observe these events within a cellular
      environment. A technique for monitoring whole-cell mitochondrial dynamics has
      been in use for some time and is based on a mitochondrially-targeted
      photoactivatable GFP (mtPAGFP). Upon expression of the mtPAGFP, a small portion
      of the mitochondrial network is photoactivated (10-20%), and the spread of the
      signal to the rest of the mitochondrial network is recorded every 15 minutes for
      1 hour using time lapse confocal imaging. Each fusion event leads to a dilution
      of signal intensity, enabling quantification of the fusion rate. Although fusion
      and fission are continuously occurring in cells, this technique only monitors
      fusion as fission does not lead to a dilution of the PAGFP signal. Co-labeling
      with low levels of TMRE (7-15 nM in INS1 cells) allows quantification of the
      membrane potential of mitochondria. When mitochondria are hyperpolarized they
      uptake more TMRE, and when they depolarize they lose the TMRE dye. Mitochondria
      that depolarize no longer have a sufficient membrane potential and tend not to
      fuse as efficiently if at all. Therefore, active fusing mitochondria can be
      tracked with these low levels of TMRE. Accumulation of depolarized mitochondria
      that lack a TMRE signal may be a sign of phototoxicity or cell death. Higher
      concentrations of TMRE render mitochondria very sensitive to laser light, and
      therefore great care must be taken to avoid overlabeling with TMRE. If the effect
      of depolarization of mitochondria is the topic of interest, a technique using
      slightly higher levels of TMRE and more intense laser light can be used to
      depolarize mitochondria in a controlled fashion (Mitra and Lippincott-Schwartz,
      2010). To ensure that toxicity due to TMRE is not an issue, we suggest exposing
      loaded cells (3-15 nM TMRE) to the imaging parameters that will be used in the
      assay (perhaps 7 stacks of 6 optical sections in a row), and assessing cell
      health after 2 hours. If the mitochondria appear too fragmented and cells are
      dying, other mitochondrial markers, such as dsRED or Mitotracker red could be
      used instead of TMRE. The mtPAGFP method has revealed details about mitochondrial
      network behavior that could not be visualized using other methods. For example,
      we now know that mitochondrial fusion can be full or transient, where matrix
      content can mix without changing the overall network morphology. Additionally, we
      know that the probability of fusion is independent of contact duration and
      organelle dimension, is influenced by organelle motility, membrane potential and
      history of previous fusion activity. In this manuscript, we describe a
      methodology for scaling up the previously published protocol using mtPAGFP and 15
      nM TMRE in order to examine multiple cells at a time and improve the time
      efficiency of data collection without sacrificing the subcellular resolution.
      This has been made possible by the use of an automated microscope stage, and
      programmable image acquisition software. Zen software from Zeiss allows the user
      to mark and track several designated cells expressing mtPAGFP. Each of these
      cells can be photoactivated in a particular region of interest, and stacks of
      confocal slices can be monitored for mtPAGFP signal as well as TMRE at specified
      intervals. Other confocal systems could be used to perform this protocol provided
      there is an automated stage that is programmable, an incubator with CO2, and a
      means by which to photoactivate the PAGFP; either a multiphoton laser, or a 405
      nm diode laser.

PMID- 22847389
TI  - Design and application of a data-independent precursor and product ion
      repository.
AB  - The functional design and application of a data-independent LC-MS precursor and
      product ion repository for protein identification, quantification, and validation
      is conceptually described. The ion repository was constructed from the sequence
      search results of a broad range of discovery experiments investigating various
      tissue types of two closely related mammalian species. The relative high degree
      of similarity in protein complement, ion detection, and peptide and protein
      identification allows for the analysis of normalized precursor and product ion
      intensity values, as well as standardized retention times, creating a
      multidimensional/orthogonal queryable, qualitative, and quantitative space.
      Peptide ion map selection for identification and quantification is primarily
      based on replication and limited variation. The information is stored in a
      relational database and is used to create peptide- and protein-specific fragment
      ion maps that can be queried in a targeted fashion against the raw or time
      aligned ion detections. These queries can be conducted either individually or as
      groups, where the latter affords pathway and molecular machinery analysis of the
      protein complement. The presented results also suggest that peptide ionization
      and fragmentation efficiencies are highly conserved between experiments and
      practically independent of the analyzed biological sample when using similar
      instrumentation. Moreover, the data illustrate only minor variation in ionization
      efficiency with amino acid sequence substitutions occurring between species.
      Finally, the data and the presented results illustrate how LC-MS performance
      metrics can be extracted and utilized to ensure optimal performance of the
      employed analytical workflows.

PMID- 22847390
TI  - Lipopeptides from the banyan endophyte, Bacillus subtilis K1: mass spectrometric
      characterization of a library of fengycins.
AB  - Mass spectrometric analysis of a banyan endophyte, Bacillus subtilis K1, extract
      showing broad spectrum antifungal activity revealed a complex mixture of
      lipopeptides, iturins, surfactins, and fengycins. Fractionation by reversed-phase
      high performance liquid chromatography (HPLC) facilitated a detailed analysis of
      fengycin microheterogeneity. Matrix assisted laser desorption ionization (MALDI)
      and electrospray ionization (ESI) mass spectrometric studies permitted the
      identification of several new fengycin variants. Four major sites of
      heterogeneity are identified: (1) N-terminus beta-hydroxy fatty acid moiety,
      where chain length variation and the presence of unsaturation occur, (2) position
      6 (Ala/Val/Ile/Leu), (3) position 10 (Val/Ile) within the macrocyclic ring, and
      (4) Gln to Glu replacement at position 8, resulting in fengycin variants that
      differ in mass by 1 Da. Diagnostic fragment ions provide a quick method for
      localizing the sites of variation in the macrocycle or the linear segment.
      Subsequent establishment of the sequences is achieved by MS/MS analysis of linear
      fengycin species produced by hydrolysis of the macrocyclic lactone. Unsaturation
      in the fatty acid chain and the presence of linear precursors in the B. subtilis
      K1 extract are also established by mass spectrometry. The anomalous distribution
      of intensities within isotopic multiplets is a diagnostic for Gln/Glu
      replacements. High resolution mass spectrometry facilitates the identification of
      fengycin species differing by 1 Da by localizing the variable position
      (Gln(8)/Glu(8)) in the fengycin variants.

PMID- 22847391
TI  - Thin-layer matrix sublimation with vapor-sorption induced co-crystallization for
      sensitive and reproducible SAMDI-TOF MS analysis of protein biosensors.
AB  - Coupling immunoassays on self-assembled monolayers (SAMs) to matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)
      provides improved assay selectivity compared with traditional photometric
      detection techniques. We show that thin-layer-transfer (TLT) of alpha-cyano-4
      hydroxycinnaminic acid (CHCA) MALDI matrix via vacuum sublimation followed by
      organic solvent-based vapor-sorption induced co-crystallization (VIC) results in
      unique matrix/analyte co-crystallization tendencies that optimizes assay
      reproducibility and sensitivity. Unique matrix crystal morphologies resulted from
      VIC solvent vapors, indicating nucleation and crystal growth characteristics
      depend upon VIC parameters. We observed that CHCA microcrystals generated by
      methanol VIC resulted in >10* better sensitivity, increased analyte charging, and
      improved precision compared with dried droplet measurements. The uniformity of
      matrix/analyte co-crystallization across planar immunoassays directed at intact
      proteins yielded low spectral variation for single shot replicates (18.5 %
      relative standard deviation, RSD) and signal averaged spectra (<10 % RSD). We
      envision that TLT and VIC for MALDI-TOF will enable high-throughput, reproducible
      array-based immunoassays for protein molecular diagnostic assays in diverse
      biochemical and clinical applications.

PMID- 22847393
TI  - Relationship between endothelial functions and acetylsalicylic acid resistance in
      newly diagnosed hypertensive patients.
AB  - BACKGROUND: We aimed to investigate the effects and dose dependency of aspirin on
      endothelial functions and prevalence of aspirin resistance in newly diagnosed
      hypertensive patients without previous drug therapy and development of cardiac
      complications. HYPOTHESIS: Acetylsalicyclic acid improves endothelial function.
      METHODS: Fifty-eight hypertensive patients and 61 healthy subjects in the control
      group were included in the study. Endothelial functions of the patient and
      control groups were evaluated with brachial artery examination. Patient and
      control groups were divided into 2 groups. A total of 100 mg and 300 mg of
      aspirin were given to the separate groups for 1 week. After 1 week, endothelial
      functions were reevaluated and aspirin resistance examined with a platelet
      function analyzer (PFA-100; Dade Behring, Marbourg, Germany). RESULTS: Baseline
      flow-mediated dilatation (FMD) change percent in hypertensive patients was 9.8%,
      and it was significantly lower than in the control group (12%) (P < 0.001).
      Frequency of acetylsalicylic acid (ASA) resistance was 20% and 26% in control and
      hypertensive patient groups, respectively (P = not significant). ASA resistance
      was 28% and 24% in 100 mg and 300 mg in hypertensive patients, respectively (P =
      not significant). FMD change percent increased both in the control and
      hypertensive groups after ASA treatment from 12.4% to 13.3% and 9.8 % to 11.9 %,
      respectively. FMD percentage change was significantly increased in hypertensive
      patients irrespective of ASA resistance (P = 0.02, for ASA resistance [+]; P <
      0.012, for ASA resistance [-]). CONCLUSIONS: Endothelial functions were impaired
      more in hypertensive patients compared to the control group. Endothelial
      functions were improved with all ASA doses in hypertensive patients irrespective
      of ASA resistance.

PMID- 22847392
TI  - Analysis of renal cell carcinoma as a first step for developing mass spectrometry
      based diagnostics.
AB  - Immediate diagnosis of human specimen is an essential prerequisites in medical
      routines. This study aimed to establish a novel cancer diagnostics system based
      on probe electrospray ionization-mass spectrometry (PESI-MS) combined with
      statistical data processing. PESI-MS uses a very fine acupuncture needle as a
      probe for sampling as well as for ionization. To demonstrate the applicability of
      PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell
      carcinoma (ccRCC) by PESI-MS and processed the data by principal components
      analysis (PCA). Our system successfully delineated the differences in lipid
      composition between non-cancerous and cancerous regions. In this case,
      triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine
      different individuals, the result being consistent with well-known profiles of
      ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous
      regions based on the expression of TAG. These results strongly suggest that PESI
      MS will be applicable to cancer diagnosis, especially when the number of data is
      augmented.

PMID- 22847394
TI  - The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder
      (OAB) by racial/ethnic group and age: results from OAB-POLL.
AB  - AIMS: To estimate the prevalence of LUTS and OAB in a large, ethnically diverse
      US study. METHODS: This cross-sectional, population-representative survey was
      conducted via the Internet in the US among 10,000 men and women aged 18-70 (2,000
      African-Americans [AA], 2,000 Hispanics, 6,000 whites). The LUTS tool assessed
      how often participants experienced LUTS during the past 4 weeks on a five-point
      Likert scale. OAB was defined by the presence of urinary urgency >= "sometimes"
      or >= "often," and/or the presence of urgency urinary incontinence (UUI).
      Descriptive statistics were used to evaluate group differences. Logistic
      regression analyses were conducted to examine the impact of racial/ethnic group
      on OAB. RESULTS: Response rate, 56.7%. Prevalent LUTS included terminal dribble
      and nocturia across gender, post-micturition leaking (men), and stress
      incontinence (women). Prevalence of OAB >= "sometimes" and >= "often" were 17%
      and 8% in men and 30% and 20% in women--with significantly higher rates among AA
      men and women. A similar trend was found for UUI among men (AA, 10%; Hispanic and
      whites, 6%), while AA and white women had higher prevalence of UUI (19%) as
      compared to Hispanic women (16%). In logistic regression analyses, AA and
      Hispanic men and women were significantly more likely than whites to have OAB
      despite having lower prevalence of self-reported comorbid conditions and risk
      factors. CONCLUSIONS: LUTS and OAB are highly prevalent in both men and women and
      increase with advancing age. Further, racial/ethnic group is a robust predictor
      of OAB in men and women.

PMID- 22847395
TI  - An examination of aneurysm rerupture rates with epsilon aminocaproic acid.
AB  - BACKGROUND: Epsilon aminocaproic acid (EACA) has been used in the past to prevent
      cerebral aneurysm rerupture. Recent studies have indicated that short-term
      treatment with EACA can lower rebleeding rates without significantly increasing
      ischemic or thrombotic complications or permanent shunt rates. The goal of this
      study is to determine the efficacy of EACA in the prevention of aneurysm
      rerupture at a high volume subarachnoid hemorrhage center. METHODS: We conducted
      a retrospective study of 355 consecutive subarachnoid hemorrhage patients over a
      2-year period under our current protocol for EACA use. Patients were divided by
      presentation time to our institution and whether the patient received EACA. The
      primary endpoints of the study were rebleeding rates, ischemic complications,
      thrombotic complications, vasospasm, shunt rates, and outcomes. RESULTS:
      Rerupture rates were reduced by half in the entire pool of patients on EACA after
      controlling for Hunt and Hess Scores and Fisher Scores. In patients who received
      early aneurysm treatment, this effect persisted but was non-statistically
      significant due to the small numbers of reruptures. In addition, there was no
      evidence to suggest that EACA increased ischemic or thrombotic complications,
      vasospasm, or VPS rates. In patients presenting earlier than 24 h to our
      institution, there was a non-significant trend toward worse outcomes after EACA
      use. This trend was reversed in patients arriving after 24 h. CONCLUSION: There
      is evidence to suggest that EACA is protective from aneurysm rerupture without
      significant ischemic or thrombotic complications when used for less than 72 h.
      However, if the aneurysm is treated, this effect is modest indicating that early
      aneurysm treatment remains the gold standard for rerupture prevention.

PMID- 22847396
TI  - Propofol infusion syndrome heralded by ECG changes.
AB  - BACKGROUND: Propofol infusion syndrome (PRIS) is well known, often associated
      with, lethal complication of sedation with propofol. PRIS seems to be associated
      with young age, traumatic brain injury (TBI), higher cumulative doses of
      propofol, and the concomitant use of catecholamines. Known manifestations of PRIS
      are metabolic acidosis, rhabdomyolysis, and cardiac failure. While fatal PRIS can
      occur suddenly and rapidly, there is no sensitive test or early warning sign, and
      the only preventive measure is to limit propofol dosage and its duration.
      METHODS: DESCRIPTION OF A SINGLE CASE: A case report was used for investigation
      purposes of this study. RESULTS: We report the case study of a young patient with
      severe TBI, receiving propofol sedation because of high intracranial pressure.
      Seven days after the trauma, the patient developed metabolic acidosis and
      refractory circulatory shock, probably caused by PRIS. Reversal of T-waves was
      seen on the electrocardiogram (ECG) 29 h before circulation failure occurred. In
      the absence of other signs of cardiac dysfunction or ischemia, these reversed T
      waves probably represent an early warning sign of developing PRIS. CONCLUSION:
      From the findings of this study, we conclude that meticulous observation and
      analysis of the ECG during propofol sedation might result in earlier recognition
      of developing PRIS.

PMID- 22847397
TI  - Platelet dysfunction is an early marker for traumatic brain injury-induced
      coagulopathy.
AB  - BACKGROUND: The goal of this study is to determine the presence of platelet
      dysfunction in patients with traumatic brain injury (TBI). The mechanisms
      underlying the coagulopathy associated with TBI remain elusive. The question of
      platelet dysfunction in TBI is unclear. METHODS: This was a prospective
      observational study conducted at Memorial Hospital of South Bend, IN, and Denver
      Health Medical Center, CO. A total of 50 patients sustaining TBI, and not under
      treatment with anticoagulants or platelet inhibitors, were analyzed utilizing
      modified thromboelastography (TEG) with platelet mapping (TEG/PM), along with
      standard coagulation tests. RESULTS: Compared to normal controls, patients with
      severe TBI had a significantly increased percentage of platelet ADP and
      arachidonic acid (AA) receptor inhibition. Furthermore, the percentage of ADP
      inhibition distinguished between survivors and non-survivors in patients with TBI
      (Mann-Whitney test, P = 0.035). ADP inhibition correlates strongly with severity
      of TBI (Mann-Whitney test, P = 0.014), while AA inhibition did not. CONCLUSION:
      These data indicate that early platelet dysfunction is prevalent after severe
      TBI, can be measured in a point-of-care setting using TEG/PM, and correlates with
      mortality. The mechanism responsible for this platelet dysfunction and associated
      implications for TBI management remains to be defined.

PMID- 22847398
TI  - Cognitive decline and hypersomnolence: thalamic manifestations of a tentorial
      dural arteriovenous fistula (dAVF).
AB  - BACKGROUND: Intracranial dural arteriovenous fistulas (dAVFs) often present with
      pulsatile tinnitus, orbital congestion, and headache. Occasionally, they present
      with focal neurologic deficits, a dementia-like syndrome, hemorrhage, or ischemic
      infarction. METHODS: This study is based on the case of a 71-year-old gentleman
      who presented with 6 months of progressive forgetfulness, inattention, and
      hypersomnolence. Four weeks prior to presentation, he developed symptoms of left
      sided pain, numbness, and worsening weakness. Neurologic examination demonstrated
      hypersomnolence, a score of 30/38 on the Kokmen Short Test of Mental Status, and
      left hemiparesis. MRI brain revealed bilateral thalamic T2 hyperintensities with
      associated enhancement. MR venogram (MRV) showed a vascular malformation in the
      posterior fossa and occlusion of the straight sinus. Conventional cerebral
      angiogram confirmed a tentorial dAVF. The dAVF was definitively treated with
      transarterial embolization, followed by clip ligation of the arterialized
      draining vein. Twelve weeks later, there was clinical resolution of left
      hemiparesis and improvement in cognitive status. MRI revealed complete resolution
      of the thalamic hyperintensities. MRV demonstrated recanalization of the straight
      sinus. RESULTS: Intracranial dAVFs are uncommon but potentially life-threatening
      acquired vascular malformations. The initiating factor is venous hypertension,
      causing retrograde flow, venous congestion, ischemia, and sometimes infarction.
      The spectrum of clinical manifestations in dAVFs reflects the degree of venous
      congestion present. If retrograde venous flow is surgically obliterated, then
      venous hypertension may be reversible. Bilateral thalamic venous congestion can
      present as a thalamic dementia. CONCLUSION: We conclude that intracranial dAVFs
      with thalamic venous congestion should be considered in the diagnostic
      differential for patients who present with subacute cognitive decline and T2
      hyperintense thalamic signal change.

PMID- 22847399
TI  - Biodegradation of DDT by stimulation of indigenous microbial populations in soil
      with cosubstrates.
AB  - Stimulation of native microbial populations in soil by the addition of small
      amounts of secondary carbon sources (cosubstrates) and its effect on the
      degradation and theoretical mineralization of DDT [l,l,l-trichloro-2,2-bis(p
      chlorophenyl)ethane] and its main metabolites, DDD and DDE, were evaluated.
      Microbial activity in soil polluted with DDT, DDE and DDD was increased by the
      presence of phenol, hexane and toluene as cosubstrates. The consumption of DDT
      was increased from 23 % in a control (without cosubstrate) to 67, 59 and 56 % in
      the presence of phenol, hexane and toluene, respectively. DDE was completely
      removed in all cases, and DDD removal was enhanced from 67 % in the control to
      ~86 % with all substrates tested, except for acetic acid and glucose substrates.
      In the latter cases, DDD removal was either inhibited or unchanged from the
      control. The optimal amount of added cosubstrate was observed to be between 0.64
      and 2.6 mg C [Formula: see text]. The CO2 produced was higher than the
      theoretical amount for complete cosubstrate mineralization indicating possible
      mineralization of DDT and its metabolites. Bacterial communities were evaluated
      by denaturing gradient gel electrophoresis, which indicated that native soil and
      the untreated control presented a low bacterial diversity. The detected bacteria
      were related to soil microorganisms and microorganisms with known biodegradative
      potential. In the presence of toluene a bacterium related to Azoarcus, a genus
      that includes species capable of growing at the expense of aromatic compounds
      such as toluene and halobenzoates under denitrifying conditions, was detected.

PMID- 22847403
TI  - Gyrotropic response in the absence of a bias field.
AB  - Electromagnetic materials lacking local time-reversal symmetry, such as
      gyrotropic materials, are of keen interest and importance both scientifically and
      technologically. Scientifically, topologically nontrivial phenomena, such as
      photonic chiral edge states, allow for reflection-free transport even in the
      presence of large disorder. Technologically, nonreciprocal photonic devices, such
      as optical isolators and circulators, play critical roles in optical
      communication and computing technologies because of their ability to eliminate
      cross-talk and feedback. Nevertheless, most known natural materials that lack
      local time-reversal symmetry require strong external fields and function only in
      a limited range of the electromagnetic spectrum. By taking advantage of
      metamaterials capable of translating the property of unidirectional active
      electronic circuits into effective dielectric response, we introduce a microwave
      gyrotropic metamaterial that does not require an external magnetic bias. Strong
      bulk Faraday-like effects, observed in both simulations and experiments, confirm
      nonreciprocity of the effective medium. This approach is scalable to many other
      wavelengths, and it also illustrates an opportunity to synthesize exotic
      electromagnetic materials.

PMID- 22847404
TI  - A molecular method for the delivery of small molecules and proteins across the
      cell wall of algae using molecular transporters.
AB  - Interest in algae has significantly accelerated with the increasing recognition
      of their potentially unique role in medical, materials, energy, bioremediation,
      and synthetic biological research. However, the introduction of tools to study,
      control, or expand the inner-workings of algae has lagged behind. Here we
      describe a general molecular method based on guanidinium-rich molecular
      transporters (GR-MoTrs) for bringing small and large cargos into algal cells.
      Significantly, this method is shown to work in wild-type algae that have an
      intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also
      successful with less studied algae including Neochloris oleoabundans and
      Scenedesmus dimorphus thus providing a new and versatile tool for algal research.

PMID- 22847405
TI  - Liquid-infused structured surfaces with exceptional anti-biofouling performance.
AB  - Bacteria primarily exist in robust, surface-associated communities known as
      biofilms, ubiquitous in both natural and anthropogenic environments. Mature
      biofilms resist a wide range of antimicrobial treatments and pose persistent
      pathogenic threats. Treatment of adherent biofilm is difficult, costly, and, in
      medical systems such as catheters or implants, frequently impossible. At the same
      time, strategies for biofilm prevention based on surface chemistry treatments or
      surface microstructure have been found to only transiently affect initial
      attachment. Here we report that Slippery Liquid-Infused Porous Surfaces (SLIPS)
      prevent 99.6% of Pseudomonas aeruginosa biofilm attachment over a 7-d period, as
      well as Staphylococcus aureus (97.2%) and Escherichia coli (96%), under both
      static and physiologically realistic flow conditions. In contrast, both
      polytetrafluoroethylene and a range of nanostructured superhydrophobic surfaces
      accumulate biofilm within hours. SLIPS show approximately 35 times the reduction
      of attached biofilm versus best case scenario, state-of-the-art PEGylated
      surface, and over a far longer timeframe. We screen for and exclude as a factor
      cytotoxicity of the SLIPS liquid, a fluorinated oil immobilized on a structured
      substrate. The inability of biofilm to firmly attach to the surface and its
      effective removal under mild flow conditions (about 1 cm/s) are a result of the
      unique, nonadhesive, "slippery" character of the smooth liquid interface, which
      does not degrade over the experimental timeframe. We show that SLIPS-based
      antibiofilm surfaces are stable in submerged, extreme pH, salinity, and UV
      environments. They are low-cost, passive, simple to manufacture, and can be
      formed on arbitrary surfaces. We anticipate that our findings will enable a broad
      range of antibiofilm solutions in the clinical, industrial, and consumer spaces.

PMID- 22847406
TI  - Scaling metagenome sequence assembly with probabilistic de Bruijn graphs.
AB  - Deep sequencing has enabled the investigation of a wide range of environmental
      microbial ecosystems, but the high memory requirements for de novo assembly of
      short-read shotgun sequencing data from these complex populations are an
      increasingly large practical barrier. Here we introduce a memory-efficient graph
      representation with which we can analyze the k-mer connectivity of metagenomic
      samples. The graph representation is based on a probabilistic data structure, a
      Bloom filter, that allows us to efficiently store assembly graphs in as little as
      4 bits per k-mer, albeit inexactly. We show that this data structure accurately
      represents DNA assembly graphs in low memory. We apply this data structure to the
      problem of partitioning assembly graphs into components as a prelude to assembly,
      and show that this reduces the overall memory requirements for de novo assembly
      of metagenomes. On one soil metagenome assembly, this approach achieves a nearly
      40-fold decrease in the maximum memory requirements for assembly. This
      probabilistic graph representation is a significant theoretical advance in
      storing assembly graphs and also yields immediate leverage on metagenomic
      assembly.

PMID- 22847408
TI  - Simulated versus observed patterns of warming over the extratropical Northern
      Hemisphere continents during the cold season.
AB  - A suite of the historical simulations run with the Intergovernmental Panel on
      Climate Change Fourth Assessment Report (IPCC AR4) models forced by greenhouse
      gases, aerosols, stratospheric ozone depletion, and volcanic eruptions and a
      second suite of simulations forced by increasing CO(2) concentrations alone are
      compared with observations for the reference interval 1965-2000. Surface air
      temperature trends are disaggregated by boreal cold (November-April) versus warm
      (May-October) seasons and by high latitude northern (N: 40 degrees -90  degrees
      N) versus southern (S: 60  degrees S-40  degrees N) domains. A dynamical
      adjustment is applied to remove the component of the cold-season surface air
      temperature trends (over land areas poleward of 40  degrees N) that are
      attributable to changing atmospheric circulation patterns. The model simulations
      do not simulate the full extent of the wintertime warming over the high-latitude
      Northern Hemisphere continents during the later 20th century, much of which was
      dynamically induced. Expressed as fractions of the concurrent trend in global
      mean sea surface temperature, the relative magnitude of the dynamically induced
      wintertime warming over domain N in the observations, the simulations with
      multiple forcings, and the runs forced by the buildup of greenhouse gases only is
      721, and roughly comparable to the relative magnitude of the concurrent sea-level
      pressure trends. These results support the notion that the enhanced wintertime
      warming over high northern latitudes from 1965 to 2000 was mainly a reflection of
      unforced variability of the coupled climate system. Some of the simulations
      exhibit an enhancement of the warming along the Arctic coast, suggestive of
      exaggerated feedbacks.

PMID- 22847407
TI  - Naturally evolved G protein-coupled receptors adopt metastable conformations.
AB  - A wide range of membrane receptors signal through conformational changes, and the
      resulting protein conformational flexibility often hinders their structural
      studies. Because the determinants of membrane receptor conformational stability
      are still poorly understood, identifying a minimal set of perturbations
      stabilizing a membrane protein in a given conformation remains a major challenge
      in membrane protein structure determination. We present a novel approach
      integrating bioinformatics, computational design and experimental techniques that
      identifies and stabilizes metastable receptor regions. When applied to the beta1
      adrenergic receptor, the method generated 13 novel receptor variants stabilized
      in the intended inactive state among which two exhibit an apparent
      thermostability higher than WT and M23 (a receptor variant previously stabilized
      by extensive scanning mutagenesis) by more than 30  degrees C and 11  degrees C,
      respectively. Targeted regions involve nonconserved unsatisfied polar residues or
      exhibit significant packing defects, features found in all class A G protein
      coupled receptor structures. These findings suggest that natural G protein
      coupled receptor sequences have evolved to be conformationally metastable through
      the design of suboptimal polar and van der Waals tertiary interactions. Given
      sufficiently accurate structural models, our approach should prove useful for
      designing stabilized variants of many uncharacterized membrane receptors.

PMID- 22847409
TI  - Virtual melting as a new mechanism of stress relaxation under high strain rate
      loading.
AB  - Generation and motion of dislocations and twinning are the main mechanisms of
      plastic deformation. A new mechanism of plastic deformation and stress relaxation
      at high strain rates (10(9)-10(12) s(-1)) is proposed, under which virtual
      melting occurs at temperatures much below the melting temperature. Virtual
      melting is predicted using a developed, advanced thermodynamic approach and
      confirmed by large-scale molecular dynamics simulations of shockwave propagation
      and quasi-isentropic compression in both single and defective crystals. The work
      and energy of nonhydrostatic stresses at the shock front drastically increase the
      driving force for melting from the uniaxially compressed solid state, reducing
      the melting temperature by 80% or 4,000 K. After melting, the relaxation of
      nonhydrostatic stresses leads to an undercooled and unstable liquid, which
      recrystallizes in picosecond time scales to a hydrostatically loaded crystal.
      Characteristic parameters for virtual melting are determined from molecular
      dynamics simulations of Cu shocked/compressed along the <110> and <111>
      directions and Al shocked/compressed along the <110> direction.

PMID- 22847410
TI  - Protective immunity to Schistosoma haematobium infection is primarily an anti
      fecundity response stimulated by the death of adult worms.
AB  - Protective immunity against human schistosome infection develops slowly, for
      reasons that are not yet fully understood. For many decades, researchers have
      attempted to infer properties of the immune response from epidemiological
      studies, with mathematical models frequently being used to bridge the gap between
      immunological theory and population-level data on schistosome infection and
      immune responses. Here, building upon earlier model findings, stochastic
      individual-based models were used to identify model structures consistent with
      observed field patterns of Schistosoma haematobium infection and antibody
      responses, including their distributions in cross-sectional surveys, and the
      observed treatment-induced antibody switch. We found that the observed patterns
      of infection and antibody were most consistent with models in which a long-lived
      protective antibody response is stimulated by the death of adult S. haematobium
      worms and reduces worm fecundity. These findings are discussed with regard to
      current understanding of human immune responses to schistosome infection.

PMID- 22847411
TI  - Nonnative interactions regulate folding and switching of myristoylated protein.
AB  - We present an integrated experimental and computational study of the molecular
      mechanisms by which myristoylation affects protein folding and function, which
      has been little characterized to date. Myristoylation, the covalent linkage of a
      hydrophobic C14 fatty acyl chain to the N-terminal glycine in a protein, is a
      common modification that plays a critical role in vital regulated cellular
      processes by undergoing reversible energetic and conformational switching. Coarse
      grained folding simulations for the model pH-dependent actin- and membrane
      binding protein hisactophilin reveal that nonnative hydrophobic interactions of
      the myristoyl with the protein as well as nonnative electrostatic interactions
      have a pronounced effect on folding rates and thermodynamic stability. Folding
      measurements for hydrophobic residue mutations of hisactophilin and atomistic
      simulations indicate that the nonnative interactions of the myristoyl group in
      the folding transition state are nonspecific and robust, and so smooth the energy
      landscape for folding. In contrast, myristoyl interactions in the native state
      are highly specific and tuned for sensitive control of switching functionality.
      Simulations and amide hydrogen exchange measurements provide evidence for
      increases as well as decreases in stability localized on one side of the
      myristoyl binding pocket in the protein, implicating strain and altered dynamics
      in switching. The effects of folding and function arising from myristoylation are
      profoundly different from the effects of other post-translational modifications.

PMID- 22847413
TI  - Quantum oscillations in YBa2Cu3O(6+delta) from period-8 d-density wave order.
AB  - We consider quantum oscillation experiments in YBa(2)Cu(3)O(6+delta) from the
      perspective of Fermi surface reconstruction using an exact transfer matrix method
      and the Pichard-Landauer formula for the conductivity. The specific density wave
      order responsible for reconstruction is a period-8 d-density wave in which the
      current density is unidirectionally modulated, which is also naturally
      accompanied by a period-4 charge order, consistent with recent nuclear magnetic
      resonance experiments. This scenario leads to a natural explanation as to why
      only oscillations from a single electron pocket of a frequency of about 500 T is
      observed, and a hole pocket of roughly twice the frequency as dictated by the
      twofold commensurate order and the Luttinger sum rule is not observed. In
      contrast period-8 d-density wave leads to a hole pocket of roughly half the
      frequency of the electron pocket. The observation of this slower frequency will
      require higher, but not unrealistic, magnetic fields than those commonly
      employed. There is already some suggestion of the slower frequency in a
      measurement in fields as high as 85 T.

PMID- 22847412
TI  - Designed guanidinium-rich amphipathic oligocarbonate molecular transporters
      complex, deliver and release siRNA in cells.
AB  - The polyanionic nature of oligonucleotides and their enzymatic degradation
      present challenges for the use of siRNA in research and therapy; among the most
      notable of these is clinically relevant delivery into cells. To address this
      problem, we designed and synthesized the first members of a new class of
      guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver,
      and release siRNA in cells, resulting in robust knockdown of target protein
      synthesis in vitro as determined using a dual-reporter system. The
      organocatalytic oligomerization used to synthesize these co-oligomers is step
      economical and broadly tunable, affording an exceptionally quick strategy to
      explore chemical space for optimal siRNA delivery in varied applications. The
      speed and versatility of this approach and the biodegradability of the designed
      agents make this an attractive strategy for biological tool development, imaging,
      diagnostics, and therapeutic applications.

PMID- 22847414
TI  - Cryo-transmission electron microscopy structure of a gigadalton peptide fiber of
      de novo design.
AB  - Nature presents various protein fibers that bridge the nanometer to micrometer
      regimes. These structures provide inspiration for the de novo design of
      biomimetic assemblies, both to address difficulties in studying and understanding
      natural systems, and to provide routes to new biomaterials with potential
      applications in nanotechnology and medicine. We have designed a self-assembling
      fiber system, the SAFs, in which two small alpha-helical peptides are programmed
      to form a dimeric coiled coil and assemble in a controlled manner. The resulting
      fibers are tens of nm wide and tens of MUm long, and, therefore, comprise
      millions of peptides to give gigadalton supramolecular structures. Here, we
      describe the structure of the SAFs determined to approximately 8 A resolution
      using cryotransmission electron microscopy. Individual micrographs show clear
      ultrastructure that allowed direct interpretation of the packing of individual
      alpha-helices within the fibers, and the construction of a 3D electron density
      map. Furthermore, a model was derived using the cryotransmission electron
      microscopy data and side chains taken from a 2.3 A X-ray crystal structure of a
      peptide building block incapable of forming fibers. This was validated using
      single-particle analysis techniques, and was stable in prolonged molecular
      dynamics simulation, confirming its structural viability. The level of self
      assembly and self-organization in the SAFs is unprecedented for a designed
      peptide-based material, particularly for a system of considerably reduced
      complexity compared with natural proteins. This structural insight is a unique
      high-resolution description of how alpha-helical fibrils pack into larger protein
      fibers, and provides a basis for the design and engineering of future
      biomaterials.

PMID- 22847415
TI  - Structure of the rhesus monkey TRIM5alpha PRYSPRY domain, the HIV capsid
      recognition module.
AB  - Tripartite motif protein TRIM5alpha blocks retroviral replication after cell
      entry, and species-specific differences in its activity are determined by
      sequence variations within the C-terminal B30.2/PRYSPRY domain. Here we report a
      high-resolution structure of a TRIM5alpha PRYSPRY domain, the PRYSPRY of the
      rhesus monkey TRIM5alpha that potently restricts HIV infection, and identify
      features involved in its interaction with the HIV capsid. The extensive capsid
      binding interface maps on the structurally divergent face of the protein formed
      by hypervariable loop segments, confirming that TRIM5alpha evolution is largely
      determined by its binding specificity. Interactions with the capsid are mediated
      by flexible variable loops via a mechanism that parallels antigen recognition by
      IgM antibodies, a similarity that may help explain some of the unusual functional
      properties of TRIM5alpha. Distinctive features of this pathogen-recognition
      interface, such as structural plasticity conferred by the mobile v1 segment and
      interaction with multiple epitopes, may allow restriction of divergent
      retroviruses and increase resistance to capsid mutations.

PMID- 22847416
TI  - Aging of human short-wave cone pathways.
AB  - The retinal image is sampled concurrently, and largely independently, by three
      physiologically and anatomically distinct pathways, each with separate ON and OFF
      subdivisions. The retinal circuitry giving rise to an ON pathway receiving input
      from the short-wave-sensitive (S) cones is well understood, but the S-cone OFF
      circuitry is more controversial. Here, we characterize the temporal properties of
      putative S-cone ON and OFF pathways in younger and older observers by measuring
      thresholds for stimuli that produce increases or decreases in S-cone stimulation,
      while the middle- and long-wave-sensitive cones are unmodulated. We characterize
      the data in terms of an impulse response function, the theoretical response to a
      flash of infinitely short duration, from which the response to any temporally
      varying stimulus may be predicted. Results show that the S-cone response to
      increments is faster than to decrements, but this difference is significantly
      greater for older individuals. The impulse response function amplitudes for
      increment and decrement responses are highly correlated across individuals,
      whereas the timing is not. This strongly suggests that the amplitude is
      controlled by neural circuitry that is common to S-cone ON and OFF responses
      (photoreceptors), whereas the timing is controlled by separate postreceptoral
      pathways. The slower response of the putative OFF pathway is ascribed to
      different retinal circuitry, possibly attributable to a sign-inverting amacrine
      cell not present in the ON pathway. It is significant that this pathway is
      affected selectively in the elderly by becoming slower, whereas the temporal
      properties of the S-cone ON response are stable across the life span of an
      individual.

PMID- 22847417
TI  - Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by
      stimulating K63-linked polyubiquitination of lysine 688.
AB  - The pathogenesis of Alzheimer's disease (AD) is associated with proteolytic
      processing of the amyloid precursor protein (APP) to an amyloidogenic peptide
      termed Abeta. Although mutations in APP and the secretase enzymes that mediate
      its processing are known to result in familial forms of AD, the mechanisms
      underlying the more common sporadic forms of the disease are still unclear.
      Evidence suggests that the susceptibility of APP to amyloidogenic processing is
      related to its intracellular localization, and that secretase-independent
      degradation may prevent the formation of cytotoxic peptide fragments. Recently,
      single nucleotide polymorphisms in the UBQLN1 gene have been linked to late-onset
      AD, and its protein product, ubiquilin-1, may regulate the maturation of full
      length APP. Here we show that ubiquilin-1 inhibits the maturation of APP by
      sequestering it in the early secretory pathway, primarily within the Golgi
      apparatus. This sequestration significantly delayed the proteolytic processing of
      APP by secretases and the proteasome. These effects were mediated by ubiquilin-1
      stimulated K63-linked polyubiquitination of lysine 688 in the APP intracellular
      domain. Our results reveal the mechanistic basis by which ubiquilin-1 regulates
      APP maturation, with important consequences for the pathogenesis of late-onset
      AD.

PMID- 22847418
TI  - Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt
      wasting, volume depletion, and renal failure.
AB  - The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is
      located in close proximity to the chloride-absorbing transporter pendrin in the
      kidney distal nephron. Single deletion of pendrin or NCC does not cause salt
      wasting or excessive diuresis under basal conditions, raising the possibility
      that these transporters are predominantly active during salt depletion or in
      response to excess aldosterone. We hypothesized that pendrin and NCC compensate
      for loss of function of the other under basal conditions, thereby masking the
      role that each plays in salt absorption. To test our hypothesis, we generated
      pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO
      mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase
      in urine output under basal conditions. As a result, animals developed profound
      volume depletion, renal failure, and metabolic alkalosis without hypokalemia,
      which were all corrected with salt replacement. We propose that the combined
      inhibition of pendrin and NCC can provide a strong diuretic regimen without
      causing hypokalemia for patients with fluid overload, including patients with
      congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized
      edema.

PMID- 22847419
TI  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence
      by interacting with telomerase RNA component.
AB  - Oxidative stress regulates telomere homeostasis and cellular aging by unclear
      mechanisms. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key mediator of
      many oxidative stress responses, involving GAPDH nuclear translocation and
      induction of cell death. We report here that GAPDH interacts with the telomerase
      RNA component (TERC), inhibits telomerase activity, and induces telomere
      shortening and breast cancer cell senescence. The Rossmann fold containing NAD(+)
      binding region on GAPDH is responsible for the interaction with TERC, whereas a
      lysine residue in the GAPDH catalytic domain is required for inhibiting
      telomerase activity and disrupting telomere maintenance. Furthermore, the GAPDH
      substrate glyceraldehyde-3-phosphate (G3P) and the nitric oxide donor S
      nitrosoglutathione (GSNO) both negatively regulate GAPDH inhibition of telomerase
      activity. Thus, we demonstrate that GAPDH is regulated to target the telomerase
      complex, resulting in an arrest of telomere maintenance and cancer cell
      proliferation.

PMID- 22847420
TI  - Early evidence of San material culture represented by organic artifacts from
      Border Cave, South Africa.
AB  - Recent archaeological discoveries have revealed that pigment use, beads,
      engravings, and sophisticated stone and bone tools were already present in
      southern Africa 75,000 y ago. Many of these artifacts disappeared by 60,000 y
      ago, suggesting that modern behavior appeared in the past and was subsequently
      lost before becoming firmly established. Most archaeologists think that San
      hunter-gatherer cultural adaptation emerged 20,000 y ago. However, reanalysis of
      organic artifacts from Border Cave, South Africa, shows that the Early Later
      Stone Age inhabitants of this cave used notched bones for notational purposes,
      wooden digging sticks, bone awls, and bone points similar to those used by San as
      arrowheads. A point is decorated with a spiral groove filled with red ochre,
      which closely parallels similar marks that San make to identify their arrowheads
      when hunting. A mixture of beeswax, Euphorbia resin, and possibly egg, wrapped in
      vegetal fibers, dated to ~40,000 BP, may have been used for hafting. Ornaments
      include marine shell beads and ostrich eggshell beads, directly dated to ~42,000
      BP. A digging stick, dated to ~39,000 BP, is made of Flueggea virosa. A wooden
      poison applicator, dated to ~24,000 BP, retains residues with ricinoleic acid,
      derived from poisonous castor beans. Reappraisal of radiocarbon age estimates
      through bayesian modeling, and the identification of key elements of San material
      culture at Border Cave, places the emergence of modern hunter-gatherer
      adaptation, as we know it, to ~44,000 y ago.

PMID- 22847421
TI  - Pathological crystallization of human immunoglobulins.
AB  - Condensation of Igs has been observed in pharmaceutical formulations and in vivo
      in cases of cryoglobulinemia. We report a study of monoclonal IgG cryoglobulins
      overexpressed by two patients with multiple myeloma. These cryoglobulins form
      crystals, and we measured their solubility lines. Depending on the
      supersaturation, we observed a variety of condensate morphologies consistent with
      those reported in clinical investigations. Remarkably, the crystallization can
      occur at quite low concentrations. This suggests that, even within the regular
      immune response to infections, cryoprecipitation of Ig can be possible.

PMID- 22847422
TI  - Molecular basis for the action of the collagen-specific chaperone Hsp47/SERPINH1
      and its structure-specific client recognition.
AB  - Collagen is the most abundant protein in animals and is a major component of the
      extracellular matrix in tissues such as skin and bone. A distinctive structural
      feature of all collagen types is a unique triple-helical structure formed by
      tandem repeats of the consensus sequence Xaa-Yaa-Gly, in which Xaa and Yaa
      frequently are proline and hydroxyproline, respectively. Hsp47/SERPINH1 is a
      procollagen-specific molecular chaperone that, unlike other chaperones,
      specifically recognizes the folded conformation of its client. Reduced functional
      levels of Hsp47 were reported in severe recessive forms of osteogenesis
      imperfecta, and homozygous knockout is lethal in mice. Here we present crystal
      structures of Hsp47 in its free form and in complex with homotrimeric synthetic
      collagen model peptides, each comprising one Hsp47-binding site represented by an
      arginine at the Yaa-position of a Xaa-Yaa-Gly triplet. Two of these three binding
      sites in the triple helix are occupied by Hsp47 molecules, which bind in a head
      to-head fashion, thus making extensive contacts with the leading and trailing
      strands of the collagen triple helix. The important arginine residue within the
      Xaa-Arg-Gly triplet is recognized by a conserved aspartic acid. The structures
      explain the stabilization of the triple helix as well as the inhibition of
      collagen-bundle formation by Hsp47. In addition, we propose a pH-dependent
      substrate release mechanism based on a cluster of histidine residues.

PMID- 22847423
TI  - Autophagic activity dictates the cellular response to oncogenic RAS.
AB  - RAS is frequently mutated in human cancers and has opposing effects on autophagy
      and tumorigenesis. Identifying determinants of the cellular responses to RAS is
      therefore vital in cancer research. Here, we show that autophagic activity
      dictates the cellular response to oncogenic RAS. N-terminal Apoptosis-stimulating
      of p53 protein 2 (ASPP2) mediates RAS-induced senescence and inhibits autophagy.
      Oncogenic RAS-expressing ASPP2((Delta3/Delta3)) mouse embryonic fibroblasts that
      escape senescence express a high level of ATG5/ATG12. Consistent with the notion
      that autophagy levels control the cellular response to oncogenic RAS,
      overexpressing ATG5, but not autophagy-deficient ATG5 mutant K130R, bypasses RAS
      induced senescence, whereas ATG5 or ATG3 deficiency predisposes to it.
      Mechanistically, ASPP2 inhibits RAS-induced autophagy by competing with ATG16 to
      bind ATG5/ATG12 and preventing ATG16/ATG5/ATG12 formation. Hence, ASPP2 modulates
      oncogenic RAS-induced autophagic activity to dictate the cellular response to
      RAS: to proliferate or senesce.

PMID- 22847424
TI  - Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading
      and adhesion.
AB  - Chemotaxis depends on a network of parallel pathways that coordinate cytoskeletal
      events to bias cell movement along a chemoattractant gradient. Using a forward
      genetic screen in Dictyostelium discoideum, we identified the Ste20 kinase KrsB,
      a homolog of tumor suppressors Hippo and MST1/2, as a negative regulator of cell
      spreading and substrate attachment. The excessive adhesion of krsB(-) cells
      reduced directional movement and prolonged the streaming phase of multicellular
      aggregation. These phenotypes depended on an intact kinase domain and
      phosphorylation of a conserved threonine (T176) within the activation loop.
      Chemoattractants triggered a rapid, transient autophosphorylation of T176 in a
      heterotrimeric G protein-dependent and PI3K- and TorC2-independent manner. The
      active phosphorylated form of KrsB acts to decrease adhesion to the substrate.
      Taken together these studies suggest that cycling between active and inactive
      forms of KrsB may provide the dynamic regulation of cell adhesion needed for
      proper cell migration and chemotaxis. KrsB interacts genetically with another D.
      discoideum Hippo/MST homolog, KrsA, but the two genes are not functionally
      redundant. These studies show that Hippo/MST proteins, like the tumor suppressor
      PTEN and oncogenes Ras and PI3K, play a key role in cell morphological events in
      addition to their role in regulating cell growth.

PMID- 22847425
TI  - Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in
      Drosophila melanogaster.
AB  - Multicopper ferroxidases catalyze the oxidation of ferrous iron to ferric iron.
      In yeast and algae, they participate in cellular uptake of iron; in mammals, they
      facilitate cellular efflux. The mechanisms of iron metabolism in insects are
      still poorly understood, and insect multicopper ferroxidases have not been
      identified. In this paper, we present evidence that Drosophila melanogaster
      multicopper oxidase-1 (MCO1) is a functional ferroxidase. We identified candidate
      iron-binding residues in the MCO1 sequence and found that purified recombinant
      MCO1 oxidizes ferrous iron. An association between MCO1 function and iron
      homeostasis was confirmed by two observations: RNAi-mediated knockdown of MCO1
      resulted in decreased iron accumulation in midguts and whole insects, and weak
      knockdown increased the longevity of flies fed a toxic concentration of iron.
      Strong knockdown of MCO1 resulted in pupal lethality, indicating that MCO1 is an
      essential gene. Immunohistochemistry experiments demonstrated that MCO1 is
      located on the basal surfaces of the digestive system and Malpighian tubules. We
      propose that MCO1 oxidizes ferrous iron in the hemolymph and that the resulting
      ferric iron is bound by transferrin or melanotransferrin, leading to iron
      storage, iron withholding from pathogens, regulation of oxidative stress, and/or
      epithelial maturation. These proposed functions are distinct from those of other
      known ferroxidases. Given that MCO1 orthologues are present in all insect genomes
      analyzed to date, this discovery is an important step toward understanding iron
      metabolism in insects.

PMID- 22847426
TI  - Gender, social norms, and survival in maritime disasters.
AB  - Since the sinking of the Titanic, there has been a widespread belief that the
      social norm of "women and children first" (WCF) gives women a survival advantage
      over men in maritime disasters, and that captains and crew members give priority
      to passengers. We analyze a database of 18 maritime disasters spanning three
      centuries, covering the fate of over 15,000 individuals of more than 30
      nationalities. Our results provide a unique picture of maritime disasters. Women
      have a distinct survival disadvantage compared with men. Captains and crew
      survive at a significantly higher rate than passengers. We also find that: the
      captain has the power to enforce normative behavior; there seems to be no
      association between duration of a disaster and the impact of social norms; women
      fare no better when they constitute a small share of the ship's complement; the
      length of the voyage before the disaster appears to have no impact on women's
      relative survival rate; the sex gap in survival rates has declined since World
      War I; and women have a larger disadvantage in British shipwrecks. Taken
      together, our findings show that human behavior in life-and-death situations is
      best captured by the expression "every man for himself."

PMID- 22847427
TI  - Dynamics of inherently bounded histone modification domains.
AB  - A central goal of chromatin biology is to reveal how posttranslational histone
      marks modulate gene expression; however, relatively little is known about the
      spatial or temporal dynamics of these marks. We previously showed that a dynamic
      model of histone mark nucleation, propagation, and turnover fits the mean
      enrichment profiles from 99% of noncentromeric histone H3 lysine 9 trimethylation
      (H3K9me3) domains in mouse embryonic stem cells without the need for boundary or
      insulator elements. Here we report the full details of this "inherently bounded"
      model of histone modification dynamics and describe several dynamic features of
      the model using H3K9me3 as a paradigm. By analyzing the kinetic and structural
      constraints that drive formation of inherently bounded domains, we find that such
      domains are optimized when the rates of marking and turnover are comparable.
      Additionally, we find that to establish such domains, propagation of the histone
      marks must occur primarily through local contacts.

PMID- 22847429
TI  - QnAs with Baldomero M. Olivera. Interview by Beth Azar.

PMID- 22847428
TI  - CAG expansion induces nucleolar stress in polyglutamine diseases.
AB  - The cell nucleus is a major site for polyglutamine (polyQ) toxicity, but the
      underlying mechanisms involved have yet been fully elucidated. Here, we report
      that mutant RNAs that carry an expanded CAG repeat (expanded CAG RNAs) induce
      apoptosis by activating the nucleolar stress pathway in both polyQ patients and
      transgenic animal disease models. We showed that expanded CAG RNAs interacted
      directly with nucleolin (NCL), a protein that regulates rRNA transcription. Such
      RNA-protein interaction deprived NCL of binding to upstream control element (UCE)
      of the rRNA promoter, which resulted in UCE DNA hypermethylation and subsequently
      perturbation of rRNA transcription. The down-regulation of rRNA transcription
      induced nucleolar stress and provoked apoptosis by promoting physical interaction
      between ribosomal proteins and MDM2. Consequently, p53 protein was found to be
      stabilized in cells and became concentrated in the mitochondria. Finally, we
      showed that mitochondrial p53 disrupted the interaction between the antiapoptotic
      protein, Bcl-xL, and the proapoptotic protein, Bak, which then caused cytochrome
      c release and caspase activation. Our work provides in vivo evidence that
      expanded CAG RNAs trigger nucleolar stress and induce apoptosis via p53 and
      describes a polyQ pathogenic mechanism that involves the nucleolus.

PMID- 22847430
TI  - Admixture and recombination among Toxoplasma gondii lineages explain global
      genome diversity.
AB  - Toxoplasma gondii is a highly successful protozoan parasite that infects all warm
      blooded animals and causes severe disease in immunocompromised and immune-naive
      humans. It has an unusual global population structure: In North America and
      Europe, isolated strains fall predominantly into four largely clonal lineages,
      but in South America there is great genetic diversity and the North American
      clonal lineages are rarely found. Genetic variation between Toxoplasma strains
      determines differences in virulence, modulation of host-signaling pathways,
      growth, dissemination, and disease severity in mice and likely in humans. Most
      studies on Toxoplasma genetic variation have focused on either a few loci in many
      strains or low-resolution genome analysis of three clonal lineages. We use whole
      genome sequencing to identify a large number of SNPs between 10 Toxoplasma
      strains from Europe and North and South America. These were used to identify
      haplotype blocks (genomic regions) shared between strains and construct a
      Toxoplasma haplotype map. Additional SNP analysis of RNA-sequencing data of 26
      Toxoplasma strains, representing global diversity, allowed us to construct a
      comprehensive genealogy for Toxoplasma gondii that incorporates sexual
      recombination. These data show that most current isolates are recent recombinants
      and cannot be easily grouped into a limited number of haplogroups. A complex
      picture emerges in which some genomic regions have not been recently exchanged
      between any strains, and others recently spread from one strain to many others.

PMID- 22847431
TI  - Molecular basis of bacterial protein Hen1 activating the ligase activity of
      bacterial protein Pnkp for RNA repair.
AB  - Ribotoxins cleave essential RNAs for cell killing in vivo, and the bacterial
      polynucleotide kinase-phosphatase (Pnkp)/hua enhancer 1 (Hen1) complex has been
      shown to repair ribotoxin-cleaved RNAs in vitro. Bacterial Pnkp/Hen1 is
      distinguished from other RNA repair systems by performing 3'-terminal 2'-O
      methylation during RNA repair, which prevents the repaired RNA from repeated
      cleavage at the same site. To ensure the opportunity of 2'-O-methylation by
      bacterial Hen1 during RNA repair and, therefore, maintain the quality of the
      repaired RNA, Pnkp/Hen1 has evolved to require the participation of Hen1 in RNA
      ligation, because Pnkp alone is unable to carry out the reaction despite
      possessing all signature motifs of an RNA ligase. However, the precise role of
      Hen1 in RNA ligation is unknown. Here, we present the crystal structure of an
      active RNA ligase consisting of the C-terminal half of Pnkp (Pnkp-C) and the N
      terminal half of Hen1 (Hen1-N) from Clostridium thermocellum. The structure
      reveals that the N-terminal domain of Clostridium thermocellum (Cth) Hen1, shaped
      like a left hand, grabs the flexible insertion module of CthPnkp and locks its
      conformation via further interaction with the C-terminal addition module of
      CthPnkp. Formation of the CthPnkp-C/Hen1-N heterodimer creates a ligation pocket
      with a width for two strands of RNA, depth for two nucleotides, and the adenosine
      monophosphate (AMP)-binding pocket at the bottom. The structure, combined with
      functional analyses, provides insight into the mechanism of how Hen1 activates
      the RNA ligase activity of Pnkp for RNA repair.

PMID- 22847432
TI  - Border Cave and the beginning of the Later Stone Age in South Africa.
AB  - The transition from the Middle Stone Age (MSA) to the Later Stone Age (LSA) in
      South Africa was not associated with the appearance of anatomically modern humans
      and the extinction of Neandertals, as in the Middle to Upper Paleolithic
      transition in Western Europe. It has therefore attracted less attention, yet it
      provides insights into patterns of technological evolution not associated with a
      new hominin. Data from Border Cave (KwaZulu-Natal) show a strong pattern of
      technological change at approximately 44-42 ka cal BP, marked by adoption of
      techniques and materials that were present but scarcely used in the previous MSA,
      and some novelties. The agent of change was neither a revolution nor the advent
      of a new species of human. Although most evident in personal ornaments and
      symbolic markings, the change from one way of living to another was not
      restricted to aesthetics. Our analysis shows that: (i) at Border Cave two
      assemblages, dated to 45-49 and >49 ka, show a gradual abandonment of the
      technology and tool types of the post-Howiesons Poort period and can be
      considered transitional industries; (ii) the 44-42 ka cal BP assemblages are
      based on an expedient technology dominated by bipolar knapping, with microliths
      hafted with pitch from Podocarpus bark, worked suid tusks, ostrich eggshell
      beads, bone arrowheads, engraved bones, bored stones, and digging sticks; (iii)
      these assemblages mark the beginning of the LSA in South Africa; (iv) the LSA
      emerged by internal evolution; and (v) the process of change began sometime after
      56 ka.

PMID- 22847434
TI  - Swimming cells promote a dynamic environment within biofilms.

PMID- 22847435
TI  - Global economic potential for reducing carbon dioxide emissions from mangrove
      loss.
AB  - Mangroves are among the most threatened and rapidly disappearing natural
      environments worldwide. In addition to supporting a wide range of other
      ecological and economic functions, mangroves store considerable carbon. Here, we
      consider the global economic potential for protecting mangroves based exclusively
      on their carbon. We develop unique high-resolution global estimates (5' grid,
      about 9 * 9 km) of the projected carbon emissions from mangrove loss and the cost
      of avoiding the emissions. Using these spatial estimates, we derive global and
      regional supply curves (marginal cost curves) for avoided emissions. Under a
      broad range of assumptions, we find that the majority of potential emissions from
      mangroves could be avoided at less than $10 per ton of CO(2). Given the recent
      range of market price for carbon offsets and the cost of reducing emissions from
      other sources, this finding suggests that protecting mangroves for their carbon
      is an economically viable proposition. Political-economy considerations related
      to the ability of doing business in developing countries, however, can severely
      limit the supply of offsets and increases their price per ton. We also find that
      although a carbon-focused conservation strategy does not automatically target
      areas most valuable for biodiversity, implementing a biodiversity-focused
      strategy would only slightly increase the costs.

PMID- 22847436
TI  - Pore collapse underlies irreversible inactivation of TRPM2 cation channel
      currents.
AB  - The Ca(2+)-permeable cation channel transient receptor potential melastatin 2
      (TRPM2) plays a key role in pathogen-evoked phagocyte activation, postischemic
      neuronal apoptosis, and glucose-evoked insulin secretion, by linking these
      cellular responses to oxidative stress. TRPM2 channels are coactivated by binding
      of intracellular ADP ribose and Ca(2+) to distinct cytosolically accessible sites
      on the channels. These ligands likely regulate the activation gate, conserved in
      the voltage-gated cation channel superfamily, that comprises a helix bundle
      formed by the intracellular ends of transmembrane helix six of each subunit. For
      several K(+) and TRPM family channels, activation gate opening requires the
      presence of phosphatidylinositol-bisphosphate (PIP(2)) in the inner membrane
      leaflet. Most TRPM family channels inactivate upon prolonged stimulation in
      inside-out patches; this "rundown" is due to PIP(2) depletion. TRPM2 currents
      also run down within minutes, but the molecular mechanism of this process is
      unknown. Here we report that high-affinity PIP(2) binding regulates Ca(2+)
      sensitivity of TRPM2 activation. Nevertheless, TRPM2 inactivation is not due to
      PIP(2) depletion; rather, it is state dependent, sensitive to permeating ions,
      and can be completely prevented by mutations in the extracellular selectivity
      filter. Introduction of two negative charges plus a single-residue insertion, to
      mimic the filter sequence of TRPM5, results in TRPM2 channels that maintain
      unabated maximal activity for over 1 h, and display altered permeation properties
      but intact ADP ribose/Ca(2+)-dependent gating. Thus, upon prolonged stimulation,
      the TRPM2 selectivity filter undergoes a conformational change reminiscent of
      that accompanying C-type inactivation of voltage-gated K(+) channels. The
      noninactivating TRPM2 variant will be invaluable for gating studies.

PMID- 22847437
TI  - Molecular basis for the specification of floral organs by APETALA3 and
      PISTILLATA.
AB  - How different organs are formed from small sets of undifferentiated precursor
      cells is a key question in developmental biology. To understand the molecular
      mechanisms underlying organ specification in plants, we studied the function of
      the homeotic selector genes APETALA3 (AP3) and PISTILLATA (PI), which control the
      formation of petals and stamens during Arabidopsis flower development. To this
      end, we characterized the activities of the transcription factors that AP3 and PI
      encode throughout flower development by using perturbation assays as well as
      transcript profiling and genomewide localization studies, in combination with a
      floral induction system that allows a stage-specific analysis of flower
      development by genomic technologies. We discovered considerable spatial and
      temporal differences in the requirement for AP3/PI activity during flower
      formation and show that they control different sets of genes at distinct phases
      of flower development. The genomewide identification of target genes revealed
      that AP3/PI act as bifunctional transcription factors: they activate genes
      involved in the control of numerous developmental processes required for
      organogenesis and repress key regulators of carpel formation. Our results imply
      considerable changes in the composition and topology of the gene network
      controlled by AP3/PI during the course of flower development. We discuss our
      results in light of a model for the mechanism underlying sex-determination in
      seed plants, in which AP3/PI orthologues might act as a switch between the
      activation of male and the repression of female development.

PMID- 22847438
TI  - Molecular mechanism for the interaction between gibberellin and brassinosteroid
      signaling pathways in Arabidopsis.
AB  - Plant development is modulated by the convergence of multiple environmental and
      endogenous signals, and the mechanisms that allow the integration of different
      signaling pathways is currently being unveiled. A paradigmatic case is the
      concurrence of brassinosteroid (BR) and gibberellin (GA) signaling in the control
      of cell expansion during photomorphogenesis, which is supported by physiological
      observations in several plants but for which no molecular mechanism has been
      proposed. In this work, we show that the integration of these two signaling
      pathways occurs through the physical interaction between the DELLA protein GAI,
      which is a major negative regulator of the GA pathway, and BRASSINAZOLE
      RESISTANT1 (BZR1), a transcription factor that broadly regulates gene expression
      in response to BRs. We provide biochemical evidence, both in vitro and in vivo,
      indicating that GAI inactivates the transcriptional regulatory activity of BZR1
      upon their interaction by inhibiting the ability of BZR1 to bind to target
      promoters. The physiological relevance of this interaction was confirmed by the
      observation that the dominant gai-1 allele interferes with BR-regulated gene
      expression, whereas the bzr1-1D allele displays enhanced resistance to DELLA
      accumulation during hypocotyl elongation. Because DELLA proteins mediate the
      response to multiple environmental signals, our results provide an initial
      molecular framework for the integration with BRs of additional pathways that
      control plant development.

PMID- 22847439
TI  - Hypoxia suppresses conversion from proliferative arrest to cellular senescence.
AB  - Unlike reversible quiescence, cellular senescence is characterized by a large
      flat cell morphology, beta-gal staining and irreversible loss of regenerative
      (i.e., replicative) potential. Conversion from proliferative arrest to
      irreversible senescence, a process named geroconversion, is driven in part by
      growth-promoting pathways such as mammalian target of rapamycin (mTOR). During
      cell cycle arrest, mTOR converts reversible arrest into senescence. Inhibitors of
      mTOR can suppress geroconversion, maintaining quiescence instead. It was shown
      that hypoxia inhibits mTOR. Therefore, we suggest that hypoxia may suppress
      geroconversion. Here we tested this hypothesis. In HT-p21-9 cells, expression of
      inducible p21 caused cell cycle arrest without inhibiting mTOR, leading to
      senescence. Hypoxia did not prevent p21 induction and proliferative arrest, but
      instead inhibited the mTOR pathway and geroconversion. Exposure to hypoxia during
      p21 induction prevented senescent morphology and loss of regenerative potential,
      thus maintaining reversible quiescence so cells could restart proliferation after
      switching p21 off. Suppression of geroconversion was p53- and HIF-1-independent,
      as hypoxia also suppressed geroconversion in cells lacking functional p53 and HIF
      1alpha. Also, in normal fibroblasts and retinal cells, hypoxia inhibited the mTOR
      pathway and suppressed senescence caused by etoposide without affecting DNA
      damage response, p53/p21 induction and cell cycle arrest. Also hypoxia suppressed
      geroconversion in cells treated with nutlin-3a, a nongenotoxic inducer of p53, in
      cell lines susceptible to nutlin-3a-induced senescence (MEL-10, A172, and NKE).
      Thus, in normal and cancer cell lines, hypoxia suppresses geroconversion caused
      by diverse stimuli. Physiological and clinical implications of the present
      findings are discussed.

PMID- 22847440
TI  - Role of social wasps in Saccharomyces cerevisiae ecology and evolution.
AB  - Saccharomyces cerevisiae is one of the most important model organisms and has
      been a valuable asset to human civilization. However, despite its extensive use
      in the last 9,000 y, the existence of a seasonal cycle outside human-made
      environments has not yet been described. We demonstrate the role of social wasps
      as vector and natural reservoir of S. cerevisiae during all seasons. We provide
      experimental evidence that queens of social wasps overwintering as adults (Vespa
      crabro and Polistes spp.) can harbor yeast cells from autumn to spring and
      transmit them to their progeny. This result is mirrored by field surveys of the
      genetic variability of natural strains of yeast. Microsatellites and sequences of
      a selected set of loci able to recapitulate the yeast strain's evolutionary
      history were used to compare 17 environmental wasp isolates with a collection of
      strains from grapes from the same region and more than 230 strains representing
      worldwide yeast variation. The wasp isolates fall into subclusters representing
      the overall ecological and industrial yeast diversity of their geographic origin.
      Our findings indicate that wasps are a key environmental niche for the evolution
      of natural S. cerevisiae populations, the dispersion of yeast cells in the
      environment, and the maintenance of their diversity. The close relatedness of
      several wasp isolates with grape and wine isolates reflects the crucial role of
      human activities on yeast population structure, through clonal expansion and
      selection of specific strains during the biotransformation of fermented foods,
      followed by dispersal mediated by insects and other animals.

PMID- 22847441
TI  - Optogenetic control of phosphoinositide metabolism.
AB  - Phosphoinositides (PIs) are lipid components of cell membranes that regulate a
      wide variety of cellular functions. Here we exploited the blue light-induced
      dimerization between two plant proteins, cryptochrome 2 (CRY2) and the
      transcription factor CIBN, to control plasma membrane PI levels rapidly, locally,
      and reversibly. The inositol 5-phosphatase domain of OCRL (5-ptase(OCRL)), which
      acts on PI(4,5)P(2) and PI(3,4,5)P(3), was fused to the photolyase homology
      region domain of CRY2, and the CRY2-binding domain, CIBN, was fused to plasma
      membrane-targeting motifs. Blue-light illumination (458-488 nm) of mammalian
      cells expressing these constructs resulted in nearly instantaneous recruitment of
      5-ptase(OCRL) to the plasma membrane, where it caused rapid (within seconds) and
      reversible (within minutes) dephosphorylation of its targets as revealed by
      diverse cellular assays: dissociation of PI(4,5)P(2) and PI(3,4,5)P(3)
      biosensors, disappearance of endocytic clathrin-coated pits, nearly complete
      inhibition of KCNQ2/3 channel currents, and loss of membrane ruffling. Focal
      illumination resulted in local and transient 5-ptase(OCRL) recruitment and
      PI(4,5)P(2) dephosphorylation, causing not only local collapse and retraction of
      the cell edge or process but also compensatory accumulation of the PI(4,5)P(2)
      biosensor and membrane ruffling at the opposite side of the cells. Using the same
      approach for the recruitment of PI3K, local PI(3,4,5)P(3) synthesis and membrane
      ruffling could be induced, with corresponding loss of ruffling distally to the
      illuminated region. This technique provides a powerful tool for dissecting with
      high spatial-temporal kinetics the cellular functions of various PIs and
      reversibly controlling the functions of downstream effectors of these signaling
      lipids.

PMID- 22847443
TI  - Images reveal that atmospheric particles can undergo liquid-liquid phase
      separations.
AB  - A large fraction of submicron atmospheric aerosol particles contains both organic
      material and inorganic salts. As the relative humidity cycles in the atmosphere
      and the water content of the particles correspondingly changes, these mixed
      particles can undergo a range of phase transitions, possibly including liquid
      liquid phase separation. If liquid-liquid phase separation occurs, the gas
      particle partitioning of atmospheric semivolatile organic compounds, the
      scattering and absorption of solar radiation, and the reactive uptake of gas
      species on atmospheric particles may be affected, with important implications for
      climate predictions. The actual occurrence of liquid-liquid phase separation
      within individual atmospheric particles has been considered uncertain, in large
      part because of the absence of observations for real-world samples. Here, using
      optical and fluorescence microscopy, we present images that show the coexistence
      of two noncrystalline phases for real-world samples collected on multiple days in
      Atlanta, GA as well as for laboratory-generated samples under simulated
      atmospheric conditions. These results reveal that atmospheric particles can
      undergo liquid-liquid phase separations. To explore the implications of these
      findings, we carried out simulations of the Atlanta urban environment and found
      that liquid-liquid phase separation can result in increased concentrations of gas
      phase NO(3) and N(2)O(5) due to decreased particle uptake of N(2)O(5).

PMID- 22847442
TI  - c-kit+ precursors support postinfarction myogenesis in the neonatal, but not
      adult, heart.
AB  - We examined the myogenic response to infarction in neonatal and adult mice to
      determine the role of c-kit(+) cardiovascular precursor cells (CPC) that are
      known to be present in early heart development. Infarction of postnatal day 1-3 c
      kit(BAC)-EGFP mouse hearts induced the localized expansion of (c-kit)EGFP(+)
      cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis,
      and partial regeneration of the infarction, with (c-kit)EGFP(+) cells adopting
      myogenic and vascular fates. Conversely, infarction of adult mice resulted in a
      modest induction of (c-kit)EGFP(+) cells within the infarct, which did not
      express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate
      within the infarction, indicating a lack of authentic CPC. Explantation of
      infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of
      labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and
      angiogenic (neonate and adult) cells. FACS-purified (c
      kit)EGFP(+)/(alphaMHC)mCherry(-) (noncardiac) cells from microdissected infarcts
      within 6 h of infarction underwent cardiac differentiation, forming spontaneously
      beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac
      population of (c-kit)EGFP(+) myocytes within infarctions, indicating that the
      induction of undifferentiated precursors contributes to localized myogenesis.
      Thus, adult postinfarct myogenic failure is likely not due to a context-dependent
      restriction of precursor differentiation, and c-kit induction following injury of
      the adult heart does not define precursor status.

PMID- 22847444
TI  - Twin-arginine translocase mutations that suppress folding quality control and
      permit export of misfolded substrate proteins.
AB  - The bacterial twin-arginine translocation (Tat) pathway facilitates the transport
      of correctly folded proteins across the tightly sealed cytoplasmic membrane.
      Here, we report the isolation and characterization of suppressor mutations in the
      Tat translocase that allow export of misfolded proteins, which form structures
      that are not normally tolerated by the wild-type translocase. Selection of
      suppressors was enabled by a genetic assay that effectively linked in vivo
      folding and stability of a test protein with Tat export efficiency of a
      selectable marker protein, namely TEM-1 beta-lactamase. By using a test protein
      named alpha(3)B-a designed three-helix-bundle protein that forms collapsed,
      stable molten globules but lacks a uniquely folded structure-translocase mutants
      that rescued export of this protein were readily identified. Each mutant
      translocase still efficiently exported folded substrate proteins, indicating that
      the substrate specificity of suppressors was relaxed but not strictly altered. A
      subset of the suppressors could also export other misfolded proteins, such as the
      aggregation-prone alpha(3)A protein and reduced alkaline phosphatase.
      Importantly, the isolation of genetic suppressors that inactivate the Tat quality
      control mechanism provides direct evidence for the participation of the Tat
      translocase in structural proofreading of substrate proteins and reveals epitopes
      in the translocase that are important for this process.

PMID- 22847445
TI  - Mammalian ribonucleotide reductase subunit p53R2 is required for mitochondrial
      DNA replication and DNA repair in quiescent cells.
AB  - In postmitotic mammalian cells, protein p53R2 substitutes for protein R2 as a
      subunit of ribonucleotide reductase. In human patients with mutations in RRM2B,
      the gene for p53R2, mitochondrial (mt) DNA synthesis is defective, and skeletal
      muscle presents severe mtDNA depletion. Skin fibroblasts isolated from a patient
      with a lethal homozygous missense mutation of p53R2 grow normally in culture with
      an unchanged complement of mtDNA. During active growth, the four dNTP pools do
      not differ in size from normal controls, whereas during quiescence, the dCTP and
      dGTP pools decrease to 50% of the control. We investigate the ability of these
      mutated fibroblasts to synthesize mtDNA and repair DNA after exposure to UV
      irradiation. Ethidium bromide depleted both mutant and normal cells of mtDNA. On
      withdrawal of the drug, mtDNA recovered equally well in cycling mutant and
      control cells, whereas during quiescence, the mutant fibroblasts remained
      deficient. Addition of deoxynucleosides to the medium increased intracellular
      dNTP pools and normalized mtDNA synthesis. Quiescent mutant fibroblasts were also
      deficient in the repair of UV-induced DNA damage, as indicated by delayed
      recovery of dsDNA analyzed by fluorometric analysis of DNA unwinding and the more
      extensive and prolonged phosphorylation of histone H2AX after irradiation.
      Supplementation by deoxynucleosides improved DNA repair. Our results show that in
      nontransformed cells only during quiescence, protein p53R2 is required for
      maintenance of mtDNA and for optimal DNA repair after UV damage.

PMID- 22847446
TI  - The formate channel FocA exports the products of mixed-acid fermentation.
AB  - Formate is a major metabolite in the anaerobic fermentation of glucose by many
      enterobacteria. It is translocated across cellular membranes by the pentameric
      ion channel/transporter FocA that, together with the nitrite channel NirC, forms
      the formate/nitrite transporter (FNT) family of membrane transport proteins. Here
      we have carried out an electrophysiological analysis of FocA from Salmonella
      typhimurium to characterize the channel properties and assess its specificity
      toward formate and other possible permeating ions. Single-channel currents for
      formate, hypophosphite and nitrite revealed two mechanistically distinct modes of
      gating that reflect different types of structural rearrangements in the transport
      channel of each FocA protomer. Moreover, FocA did not conduct cations or divalent
      anions, but the chloride anion was identified as further transported species,
      along with acetate, lactate and pyruvate. Formate, acetate and lactate are major
      end products of anaerobic mixed-acid fermentation, the pathway where FocA is
      predominantly required, so that this channel is ideally adapted to act as a
      multifunctional export protein to prevent their intracellular accumulation.
      Because of the high degree of conservation in the residues forming the transport
      channel among FNT family members, the flexibility in conducting multiple
      molecules is most likely a general feature of these proteins.

PMID- 22847449
TI  - Functional epialleles at an endogenous human centromere.
AB  - Human centromeres are defined by megabases of homogenous alpha-satellite DNA
      arrays that are packaged into specialized chromatin marked by the centromeric
      histone variant, centromeric protein A (CENP-A). Although most human chromosomes
      have a single higher-order repeat (HOR) array of alpha satellites, several
      chromosomes have more than one HOR array. Homo sapiens chromosome 17 (HSA17) has
      two juxtaposed HOR arrays, D17Z1 and D17Z1-B. Only D17Z1 has been linked to CENP
      A chromatin assembly. Here, we use human artificial chromosome assembly assays to
      show that both D17Z1 and D17Z1-B can support de novo centromere assembly
      independently. We extend these in vitro studies and demonstrate, using
      immunostaining and chromatin analyses, that in human cells the centromere can be
      assembled at D17Z1 or D17Z1-B. Intriguingly, some humans are functional
      heterozygotes, meaning that CENP-A is located at a different HOR array on the two
      HSA17 homologs. The site of CENP-A assembly on HSA17 is stable and is transmitted
      through meiosis, as evidenced by inheritance of CENP-A location through
      multigenerational families. Differences in histone modifications are not linked
      clearly with active and inactive D17Z1 and D17Z1-B arrays; however, we detect a
      correlation between the presence of variant repeat units of D17Z1 and CENP-A
      assembly at the opposite array, D17Z1-B. Our studies reveal the presence of
      centromeric epialleles on an endogenous human chromosome and suggest genomic
      complexities underlying the mechanisms that determine centromere identity in
      humans.

PMID- 22847450
TI  - Selfish supernumerary chromosome reveals its origin as a mosaic of host genome
      and organellar sequences.
AB  - Supernumerary B chromosomes are optional additions to the basic set of A
      chromosomes, and occur in all eukaryotic groups. They differ from the basic
      complement in morphology, pairing behavior, and inheritance and are not required
      for normal growth and development. The current view is that B chromosomes are
      parasitic elements comparable to selfish DNA, like transposons. In contrast to
      transposons, they are autonomously inherited independent of the host genome and
      have their own mechanisms of mitotic or meiotic drive. Although B chromosomes
      were first described a century ago, little is known about their origin and
      molecular makeup. The widely accepted view is that they are derived from
      fragments of A chromosomes and/or generated in response to interspecific
      hybridization. Through next-generation sequencing of sorted A and B chromosomes,
      we show that B chromosomes of rye are rich in gene-derived sequences, allowing us
      to trace their origin to fragments of A chromosomes, with the largest parts
      corresponding to rye chromosomes 3R and 7R. Compared with A chromosomes, B
      chromosomes were also found to accumulate large amounts of specific repeats and
      insertions of organellar DNA. The origin of rye B chromosomes occurred an
      estimated ~1.1-1.3 Mya, overlapping in time with the onset of the genus Secale
      (1.7 Mya). We propose a comprehensive model of B chromosome evolution, including
      its origin by recombination of several A chromosomes followed by capturing of
      additional A-derived and organellar sequences and amplification of B-specific
      repeats.

PMID- 22847451
TI  - Polypyrrole nanoparticles for high-performance in vivo near-infrared photothermal
      cancer therapy.
AB  - Polypyrrole nanoparticles (PPy NPs) exhibit strong absorption in the near
      infrared (NIR) region. With an excellent photothermal efficiency of ~45% at 808
      nm, sub-100 nm PPy NPs are demonstrated to be a promising photothermal agent for
      in vivo cancer therapy using NIR irradiation.

PMID- 22847452
TI  - External validation of the preoperative Karakiewicz nomogram in a large
      multicentre series of patients with renal cell carcinoma.
AB  - PURPOSE: To perform a formal external validation of the preoperative Karakiewicz
      nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large
      series of surgically treated patients diagnosed with organ-confined or metastatic
      renal cell carcinoma (RCC). METHODS: Patient population originated from a series
      of retrospectively gathered cases that underwent radical or partial nephrectomy
      between years 1995 and 2007 for suspicion of kidney cancer. The original Cox
      coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10
      years following surgery and compared to the observed risk of CSS in the current
      population. External validation was quantified using measures of predictive
      accuracy, defined as model discrimination and calibration. RESULTS: A total of
      3,374 patients were identified. Relative to the original development cohort, the
      current sample population had a larger proportion of patients with localized
      (40.0 vs. 26.3 %, P < 0.001) and non-metastatic (92.2 vs. 88.1 %, P = 0.03)
      disease at presentation. Model discrimination for the prediction of CSS was 87.8
      % (95 % CI, 84.4-91.4) at 1 year, 87.0 % (95 % CI, 84.4-89.5) at 2 years, 84.7 %
      (95 % CI, 82.3-87.1) at 5 years, and 85.9 % (95 % CI, 83.2-88.6) at 10 years. The
      relationship between predicted and observed CSS risk was adequate in the
      calibration plot. CONCLUSION: The use of the KN for the prediction of CSS in
      patients diagnosed with renal cell carcinoma was validated in the current study.
      In consequence, this tool may be recommended for routine clinical counseling in
      patients with various stages of RCC in the preoperative setting.

PMID- 22847453
TI  - The impact of obesity on the predictive accuracy of PSA in men undergoing
      prostate biopsy.
AB  - PURPOSE: Obese men have been reported to have lower serum PSA values relative to
      normal-weight men in population-based studies, screening cohorts, and in men with
      prostate cancer (CaP) treated with surgery. There are concerns that PSA may be
      less accurate in detecting prostate cancer in men with increased body mass index
      (BMI). We determine whether the diagnostic potential of PSA is negatively
      influenced by obesity by comparing its operating characteristics across BMI
      categories among men undergoing prostate biopsy. METHODS: Demographic, clinical,
      and histopathological data on 917 men who underwent trans-rectal ultrasound
      guided prostate needle biopsy from 2002 to 2010 at a University hospital in Italy
      were used in the study. Men were categorized for BMI as follows: <25 kg/m(2)
      (normal weight), 25-29.9 kg/m(2) (overweight), and >= 30 kg/m(2) (obese).
      Receiver operator characteristics (ROC) curves were used to assess PSA accuracy
      for predicting prostate cancer overall and then stratified according to digital
      rectal examination (DRE) findings using the area under the ROC curve (AUC).
      RESULTS: The obesity rate of the study cohort was 21 %. There was no
      statistically significant difference in the overall AUCs of PSA for predicting
      CaP among normal-weight (AUC = 0.56), overweight (AUC = 0.60), and obese men (AUC
      = 0.60; p = 0.68) in either DRE-positive or negative men. CONCLUSIONS: In a
      cohort of Italian men undergoing prostate biopsy, the performance accuracy of PSA
      as a predictor of CaP is not significantly altered by BMI. Obesity does not
      negatively impact the overall ability of PSA to discriminate between CaP and
      benign conditions.

PMID- 22847455
TI  - A new isomer of C20 and a way to a new C240.
AB  - Here we show that the dynamic simulation of a molecular collision can give
      insight into new molecular species. In this way, a new stable isomer of C(20)
      (IV) has been found. It is planar with pentagonal form. This isomer is high in
      energy compared to the three most stable previously known isomers of C(20): cage
      (I), bowl (II) and ring (III). Most interestingly, we show that using this new
      isomer it is possible to construct a macrobucky C(240) (V) that is also stable.
      The electronic structure of this new isomer of C(240) is very different from
      properties of the C(240) fullerene. Contrary to the C(240) fullerene, in the new
      isomer the pi electrons are localized.

PMID- 22847454
TI  - Protective effects of transduced Tat-DJ-1 protein against oxidative stress and
      ischemic brain injury.
AB  - Reactive oxygen species (ROS) contribute to the development of a number of
      neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an
      important role in transcriptional regulation, acting as molecular chaperone and
      antioxidant. In the present study, we investigated whether DJ-1 protein shows a
      protective effect against oxidative stress-induced neuronal cell death in vitro
      and in ischemic animal models in vivo. To explore DJ-1 protein's potential role
      in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1
      fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a
      doseand time-dependent manner. Transduced Tat-DJ-1 protein increased cell
      survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular
      ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2.
      Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ
      1 protein prevented neuronal cell death induced by transient forebrain ischemia
      in the CA1 region of the hippocampus. These results demonstrate that transduced
      Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting
      that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for
      ischemic injuries related to oxidative stress.

PMID- 22847457
TI  - Effect of repeated treatment with topiramate on voluntary alcohol intake and beta
      endorphin plasma level in Warsaw alcohol high-preferring rats.
AB  - RATIONALE: Pharmacological treatment currently used for alcohol dependence is not
      sufficient for the all patients, and there is a crucial need to find more
      effective treatments. Recent studies indicate that topiramate is likely the most
      promising new medication for alcohol dependence. The rationale for topiramate as
      treatment for alcohol addiction is based on its multifaceted neurochemical
      activity that targets multiple neural pathways. OBJECTIVES: This study aims to
      assess the effect of repeated treatment with topiramate on voluntary alcohol
      intake and beta-endorphin plasma level in rats selectively bred for high alcohol
      preference. METHODS: Initially, Warsaw high preferring rats (N = 50) were given a
      24-h/day free choice between a 10 % (v/v) alcohol solution and water for three
      consecutive weeks. Subsequently, rats were administered with topiramate (40 or 80
      mg/kg b.w.) or vehicle for 14 days and ethanol intake was measured daily.
      Subsequently, we examined the effects of topiramate on plasma beta-endorphin
      levels, while alcohol was available and when it was not available for an extended
      period time. RESULTS: We observed significantly increase in the levels of beta
      endorphin in rats with free access to alcohol both in a topiramate- or vehicle
      treated group. However, in topiramate-treated group, a voluntary consumption of
      alcohol diminished in comparison with the vehicle-treated rats. CONCLUSION: The
      results from this study indicated that topiramate reduces voluntary alcohol
      intake and support our previous findings that the increase of beta-endorphin
      level is responsible at least partly for the effectiveness of drugs in treating
      the alcohol addiction.

PMID- 22847458
TI  - [Non-Q-wave-electrocardiograms. Signs of earlier myocardial infarction].
AB  - An increasing number of elderly people and diabetes patients with myocardial
      infarction go unrecognized because of painless ischemia and regression of major Q
      waves over time. An increased awareness of diagnostic electrocardiogram (ECG)
      abnormalities other than Q-waves should allow physicians to optimize patient
      management. Particularly emphasized is the R-peak delay in V6, i.e. the R-peak in
      V6 being later than the S-peak in V2, as a sign of masked anterior myocardial
      infarction and ECG findings if infarcts are masked by left ventricular hemiblocks
      and left bundle branch block (LBBB). In left anterior hemiblocks dramatically
      decreased R-waves in leads II, III and AVF in conjunction with disappearance of Q
      waves in leads I and aVL help to identify posterodiaphragmatic infarction. The
      left posterior hemiblock is itself a potent indicator of underlying
      posterodiaphragmatic infarction not recognized by Q-waves. In LBBB Cabrera's
      sign, RSR' morphology in the left-sided or inferior leads, inverse R-progression
      from V1 to V3 and primary repolarization abnormalities overlying the secondary T
      wave changes are specific indicators of myocardial infarction. QRS-prolongation
      greater than 150 ms independently identifies ventricular function impairment in
      chronic coronary heart disease.

PMID- 22847459
TI  - Recent advances in transformation optics.
AB  - Within the past a few years, transformation optics has emerged as a new research
      area, since it provides a general methodology and design tool for manipulating
      electromagnetic waves in a prescribed manner. Using transformation optics,
      researchers have demonstrated a host of striking phenomena and devices; many of
      which were only thought possible in science fiction. In this paper, we review the
      most recent advances in transformation optics. We focus on the theory, design,
      fabrication and characterization of transformation devices such as the carpet
      cloak, "Janus" lens and plasmonic cloak at optical frequencies, which allow
      routing light at the nanoscale. We also provide an outlook of the challenges and
      future directions in this fascinating area of transformation optics.

PMID- 22847460
TI  - Acute life-threatening event with peginterferon alpha-2b in a child with chronic
      hepatitis C.

PMID- 22847461
TI  - Congenital anomalies and childhood celiac disease in Sweden.
AB  - Previously, chromosomal anomalies and, to a lesser extent, other congenital
      anomalies have been associated with an increased risk of celiac disease (CD). We
      investigated these associations using a systematic approach. We identified all of
      the singleton children (792,401) born in Sweden between 1987 and 1993, and
      obtained cases of CD using the Swedish National Inpatient Registry. We applied
      Cox regression models as well as sibling designs to study the association between
      congenital anomalies and childhood CD. We observed that anomalies of face, neck,
      ear, heart, digestive tract, or chromosomes were associated with CD.

PMID- 22847462
TI  - Balloon expulsion test as a screen for outlet obstruction in children with
      chronic constipation.
AB  - OBJECTIVE: Chronic constipation (CC) is a common problem in pediatrics and is
      often the result of obstructed defecation. The aim of the present study was to
      study the feasibility and efficacy of the balloon expulsion test (BET) in the
      diagnosis and management of children with CC. METHODS: Retrospective study
      comparing BET and high-resolution anorectal manometry (ARM). The BET was done
      together with ARM in 29 children, ages 8 to 19 years, with CC. For BET, a 60-mL
      balloon was used. Passage of balloon in 1 minute or less was considered normal.
      RESULTS: Fifteen of the 29 children had a normal BET. Of these, 14 also had an
      ARM, all of which were normal (except for 2 cases with a hypertonic baseline anal
      sphincter). Thus 12 of 14 with BET and ARM were normal on both (correlation
      between the tests 86%). Of the 14 children that failed BET, 10 had distal
      abnormalities by ARM, contrast studies, EMG, or assessment by a pelvic physical
      therapist. All of the patients with a nonrelaxing sphincter or outlet obstruction
      were treated with laxatives, anal sphincter Botox, and/or pelvic physical therapy
      and biofeedback. In follow-up of at least 3 months, all of the patients with a
      failed BET were improved. CONCLUSIONS: We found a high correlation between a
      normal ARM and BET. If the BET is abnormal and the ARM does not identify a cause
      for the distal obstruction, additional studies may be needed, including contrast
      enema, defecography, or electromyography. BET appears to be a safe, reliable, and
      useful test in the evaluation and management of CC in children.

PMID- 22847463
TI  - Constipation in children with neurofibromatosis type 1.
AB  - BACKGROUND AND OBJECTIVES: Neurofibromatosis type 1 (NF1) is a hereditary,
      heterogenic, and multiorganic disease. The NF1 phenotype shows great variability
      in expressivity and often includes symptoms from the central and peripheral
      nervous systems. Bowel symptoms have been reported, but gastrointestinal function
      in NF1 remains to be described in detail. In this first systematic study of bowel
      function in children with NF1, we aimed to investigate symptoms of constipation
      and test the hypotheses that children with NF1 have abnormally large rectum and
      prolonged colonic transit time (CTT). METHODS: A total of 20 children with NF1
      (age 8.2 +/- 2.4 years) were evaluated with medical history; clinical
      examination; digital rectal examination; bowel and dietary diaries; Rome III
      criteria; measurement of rectal diameter by transabdominal ultrasound; and
      radiographic estimation of CTT. The control group for assessment of rectal
      diameter comprised 23 healthy children (mean age 9.1 +/- 2.7 years). RESULTS: A
      total of 6 children with NF1 (30%) were constipated according to Rome III
      criteria. Average rectal diameter was significantly larger than for healthy
      children (32.9 +/- 7.2 mm vs 21.4 +/- 5.9 mm, P < 0.0001). Median CTT in NF1
      children was 53 hours (range 26-101). Compared with existing normative data, CTT
      was prolonged (>84 hours) in 3 (19%). CONCLUSIONS: Symptoms of constipation were
      surprisingly common in children with NF1. Correspondingly, rectal diameters were
      abnormally large and a higher proportion than expected had prolonged CTT. The
      underlying pathophysiology remains obscure, but we hypothesise that abnormalities
      of the enteric nervous system or disturbed cellular growth could be present.

PMID- 22847464
TI  - Discordant presentation of biliary atresia in premature monozygotic twins.

PMID- 22847465
TI  - Heavy breathing:  a step to noninvasive assessment of hepatic fibrosis and
      function in infants and children.

PMID- 22847466
TI  - Outcome following aminosalicylate therapy in children newly diagnosed as having
      ulcerative colitis.
AB  - OBJECTIVES: Despite a paucity of published supporting data, 5-aminosalicylate (5
      ASA) use in pediatric ulcerative colitis (UC) is common. The present study
      describes the use and outcome of a large multicenter inception cohort of children
      with UC treated with 5-ASA. METHODS: Data were obtained from the Pediatric
      Inflammatory Bowel Disease Collaborative Research Group Registry, a prospective
      North American observational study of children newly diagnosed as having
      inflammatory bowel disease ages 16 years or younger. Patient data are recorded at
      diagnosis, 30 days, and then quarterly. Patients are managed by physician
      dictate, not protocol. Disease activity is classified by physician global
      assessment. The primary outcome examined was corticosteroid (CS) free, inactive
      UC at 1 year following initiation of 5-ASA within 30 days of diagnosis (with or
      without concomitant CS use) without the need for rescue therapy
      (immunomodulators, biologics, or colectomy). RESULTS: Study subjects included 213
      patients newly diagnosed as having UC who received oral 5-ASA compounds (115 of
      whom also received CS) during the first 30 days after diagnosis, and no other
      oral therapies for the treatment of UC. Of these 213 patients, 86 (40%) were CS
      free and physician global assessment inactive at 1 year without rescue. Outcome
      was not associated with disease severity at diagnosis, demographic or laboratory
      factors examined, or initial dose of 5-ASA used. CONCLUSIONS: Forty percent of
      children taking 5-ASA as primary maintenance therapy at diagnosis are in CS-free
      remission after 1 year of treatment. Further pediatric studies will be needed to
      address whether increased adherence and/or higher dosing schedules will improve
      outcomes.

PMID- 22847468
TI  - Reduced deformability of circulating erythrocytes: a marker of hyposplenism.

PMID- 22847467
TI  - Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and
      hepatic clockwork.
AB  - DNA methyltransferase 3B (DNMT3B) is critically involved in de novo DNA
      methylation and genomic stability, while the regulatory mechanism in liver is
      largely unknown. We previously reported that diurnal variation occurs in the mRNA
      expression of Dnmt3b in adult mouse liver. The aim of this study was to determine
      the mechanism underlying the diurnal expression pattern. The highest level and
      the lowest level of Dnmt3b mRNA expression were confirmed to occur at dawn and in
      the afternoon, respectively, and the expression pattern of Dnmt3b closely
      coincided with that of Bmal1. Since the diurnal pattern of Dnmt3b mRNA expression
      developed at weaning and scheduled feeding to separate the feeding cycle from the
      light/dark cycle led to a phase-shift in the expression, it could be assumed that
      feeding plays a critical role as an entrainment signal. In liver-specific Bmal1
      knockout (L-Bmal1 KO) mice, L-Bmal1 deficiency resulted in significantly higher
      levels of Dnmt3b at all measured time points, and the time when the expression
      was the lowest in wild-type mice was shifted to earlier. Investigation of global
      DNA methylation revealed a temporal decrease of 5-methyl-cytosine percentage in
      the genome of wild-type mice in late afternoon. By contrast, no such decrease in
      5-methyl-cytosine percentage was detected in L-Bmal1 KO mice, suggesting that
      altered Dnmt3b expression affects the DNA methylation state. Taken together, the
      results suggest that the feeding and hepatic clockwork generated by the clock
      genes, including Bmal1, regulate the diurnal variation in Dnmt3b mRNA expression
      and the consequent dynamic changes in global DNA methylation.

PMID- 22847469
TI  - Crystal arthritis: a new 'package of care' strategy for effective gout
      management.

PMID- 22847470
TI  - Connective tissue diseases: Management of lupus nephritis-new guidelines
      revealed.
AB  - The past decade has seen exciting progress in the management of lupus nephritis,
      a manifestation of systemic lupus erythematosus that accounts for its major
      morbidity and mortality. The American College of Rheumatology has issued new
      guidelines for screening and treatment of lupus nephritis, based on expert
      recommendations.

PMID- 22847471
TI  - Long-term effects of sport: preventing and managing OA in the athlete.
AB  - Sports participation is associated with an increased risk of future
      osteoarthritis (OA), much of which results from joint injury. No strong evidence
      exists that moderate sporting activity in the presence of normal joints
      predisposes to OA. Whether high-level participation in sport, particularly impact
      type sports, is truly associated with OA is unclear owing to difficulties in
      differentiating the confounding effect of joint injury. Attention to strategies
      that prevent joint injury in athletes is paramount. Evidence does support the use
      of targeted neuromuscular exercise programmes, ankle taping and/or bracing and
      equipment or rule changes to prevent joint injuries in athletes. Optimal injury
      management, including rehabilitation and surgery if appropriate, is needed to
      facilitate healing and address biomechanical and neuromuscular impairments to
      reduce the risk of re-injury and minimize the onset and extent of joint symptoms.
      Management of OA in athletes requires attention to load-reducing strategies,
      activity modification, muscle strengthening and weight control.

PMID- 22847472
TI  - A survey of diabetes prevalence in zoo-housed primates.
AB  - In humans, type II diabetes mellitus is a condition in which the pancreas is
      capable of producing insulin but cells do not appropriately respond to insulin
      with an uptake of glucose. While multiple factors are associated with type II
      diabetes in humans, a high calorie diet and limited exercise are significant risk
      factors for the development of this disease. Zoo primates, with relatively high
      caloric density diets and sedentary lifestyles, may experience similar conditions
      that could predispose them to the development of diabetes. We surveyed all
      Association of Zoos and Aquariums (AZA) facilities with primates in their
      collections to determine the prevalence of diabetes, diagnosis and treatment
      methods, and treatment outcomes. Nearly 30% of responding institutions reported
      at least one diabetic primate in their current collection. Although the majority
      of reported cases were in Old World Monkeys (51%), all major taxonomic groups
      were represented. Females represented nearly 80% of the diagnosed cases. A wide
      variety of diagnosing, monitoring, and treatment techniques were reported. It is
      clear from these results diabetes should be considered prominently in decisions
      relating to diet, weight and activity levels in zoo-housed primates, as well as
      discussions surrounding animal health and welfare.

PMID- 22847473
TI  - The effect of intermolecular hydrogen bonding on the planarity of amides.
AB  - Ab initio and density functional theory (DFT) calculations on some model systems
      are presented to assess the extent to which intermolecular hydrogen bonding can
      affect the planarity of amide groups. Formamide and urea are examined as
      archetypes of planar and non-planar amides, respectively. DFT optimisations
      suggest that appropriately disposed hydrogen-bond donor or acceptor molecules can
      induce non-planarity in formamide, with OCNH dihedral angles deviating by up to
      ca. 20 degrees  from planarity. Ab initio energy calculations demonstrate that
      the energy required to deform an amide molecule from the preferred geometry of
      the isolated molecule is more than compensated by the stabilisation due to
      hydrogen bonding. Similarly, the NH(2) group in urea can be made effectively
      planar by the presence of appropriately positioned hydrogen-bond acceptors,
      whereas hydrogen-bond donors increase the non-planarity of the NH(2) group. Small
      clusters (a dimer, two trimers and a pentamer) extracted from the crystal
      structure of urea indicate that the crystal field acts to force planarity of the
      urea molecule; however, the interaction with nearest neighbours alone is
      insufficient to induce the molecule to become completely planar, and longer-range
      effects are required. Finally, the potential for intermolecular hydrogen bonding
      to induce non-planarity in a model of a peptide is explored. Inter alia, the
      insights obtained in the present work on the extent to which the geometry of
      amide groups may be deformed under the influence of intermolecular hydrogen
      bonding provide structural guidelines that can assist the interpretation of the
      geometries of such groups in structure determination from powder X-ray
      diffraction data.

PMID- 22847474
TI  - On chip porous polymer membranes for integration of gastrointestinal tract
      epithelium with microfluidic 'body-on-a-chip' devices.
AB  - We describe a novel fabrication method that creates microporous, polymeric
      membranes that are either flat or contain controllable 3-dimensional shapes that,
      when populated with Caco-2 cells, mimic key aspects of the intestinal epithelium
      such as intestinal villi and tight junctions. The developed membranes can be
      integrated with microfluidic, multi-organ cell culture systems, providing access
      to both sides, apical and basolateral, of the 3D epithelial cell culture. Partial
      exposure of photoresist (SU-8) spun on silicon substrates creates flat membranes
      with micrometer-sized pores (0.5-4.0 MUm) that--supported by posts--span across
      50 MUm deep microfluidic chambers that are 8 mm wide and 10 long. To create three
      dimensional shapes the membranes were air dried over silicon pillars with aspect
      ratios of up to 4:1. Space that provides access to the underside of the shaped
      membranes can be created by isotropically etching the sacrificial silicon pillars
      with xenon difluoride. Depending on the size of the supporting posts and the pore
      sizes the overall porosity of the membranes ranged from 4.4 % to 25.3 %. The
      microfabricated membranes can be used for integrating barrier tissues such as the
      gastrointestinal tract epithelium, the lung epithelium, or other barrier tissues
      with multi-organ "body-on-a-chip" devices.

PMID- 22847475
TI  - Designed protein binders in combination with nanocrystalline diamond for use in
      high-sensitivity biosensors.
AB  - A platform for diagnostic applications showing signal-to-noise ratios that by far
      surpass those of traditional bioanalytical test formats has been developed. It
      combines the properties of modified nanocrystalline diamond (NCD) surfaces and
      those of polyethylene oxide and polypropylene oxide based block copolymers for
      surface passivation and binder conjugation with a new class of synthetic binders
      for proteins. The NCD surfaces were fluorine-, hydrogen-, or oxygen-terminated
      prior to further biofunctionalization and the surface composition was
      characterized by X-ray photoelectron spectroscopy. In a proof of principle
      demonstration targeting the C-reactive protein, an ELISA carried out using an F
      terminated diamond surface showed a signal-to-noise ratio of 3,900 which compares
      well to the signal-to-noise of 89 obtained in an antibody-based ELISA on a
      polystyrene microtiter plate, a standard test format used in most life science
      laboratories today. The increase in signal-to-noise ratio is to a large extent
      the result of extremely efficient passivation of the diamond surface. The results
      suggest that significant improvements can be obtained in standardized test
      formats using new materials in combination with new types of chemical coatings
      and receptor molecules.

PMID- 22847476
TI  - Direct detection of peptides and proteins on a microfluidic platform with MALDI
      mass spectrometry.
AB  - The ability to detect and quantify proteins of individual cells in high
      throughput is of enormous biological and clinical relevance. Most methods
      currently in use either require the measurement of large cell populations or are
      limited to the investigation of few cells at a time. In this report, we present
      the combination of a polydimethylsiloxane-based microfluidic device to a matrix
      assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF
      MS) that allows the detection of as few as 300 molecules at the peptide level and
      ~10(6) to 10(7) molecules at the protein level. Moreover, we performed an
      immunoassay with subsequent MALDI-TOF-MS to capture and detect insulin
      immobilized on a surface (~0.05 mm(2)) in this device with a detection limit of
      10(6) insulin molecules. This microfluidic-based approach therefore begins to
      approach the sample handling and sensitivity requirements for MS-based single
      cell analysis of proteins and peptides and holds the potential for easy
      parallelization of immunoassays and other highly sensitive protein analyses.

PMID- 22847477
TI  - Determination of the two major endocannabinoids in human plasma by MU-SPE
      followed by HPLC-MS/MS.
AB  - Endocannabinoids (ECs) are endogenous compounds that interact with type-1 and
      type-2 cannabinoid receptors (CB(1) and CB(2)), as well as non-cannabinoid
      receptors. The multitude of roles attributed to ECs makes them an emerging target
      of pharmacotherapy for a number of disparate diseases. Here a high-throughput
      bioanalytical method based on micro SPE (MU-SPE) followed by LC-MS/MS analysis
      for the simultaneous determination of the two major endocannabinoids 2
      arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide, AEA) in
      human plasma is presented. The chromatographic conditions obtained with the fused
      core column allowed a good separation in 10 min also of the AG isomers. A very
      simple and reliable extraction has been optimised by means of C18-modified tips:
      it requires only 100 MUL of plasma and allows the use of minimal volumes of
      organic solvent. The present method allows a rapid and effective clean-up, which
      also minimises the isomerisation of 2-AG. The whole procedure has been validated
      following the FDA guidelines for bioanalytical methods validation: the
      satisfactory recovery values, the negligible matrix effect and the good values of
      accuracy and reproducibility make it a simple and high-throughput analytical tool
      for clinical and biochemical studies on endocannabinoid signaling in humans.

PMID- 22847478
TI  - Enhancing the lateral-flow immunoassay for detection of proteins using an aqueous
      two-phase micellar system.
AB  - The lateral-flow (immuno)assay (LFA) has been widely investigated for the
      detection of molecular, macromolecular, and particle targets at the point-of-need
      due to its ease of use, rapid processing, and minimal power and laboratory
      equipment requirements. However, for some analytes, such as certain proteins, the
      detection limit of LFA is inferior to lab-based assays, such as the enzyme-linked
      immunosorbent assay, and needs to be improved. One solution for improving the
      detection limit of LFA is to concentrate the target protein in a solution prior
      to the detection step. In this study, a novel approach was used in the context of
      an aqueous two-phase micellar system comprised of the nonionic surfactant Triton
      X-114 to concentrate a model protein, namely transferrin, prior to LFA. Proteins
      have been shown to partition, or distribute, fairly evenly between the two phases
      of an aqueous two-phase system, which in turn results in their limited
      concentration in one of the two phases. Therefore, larger colloidal gold
      particles decorated with antibodies for transferrin were used in the
      concentration step to bind to transferrin and aid its partitioning into the top,
      micelle-poor phase. By manipulating the volume ratio of the two coexisting
      micellar phases and combining the concentration step with LFA, the transferrin
      detection limit of LFA was improved by tenfold from 0.5 to 0.05 MUg/mL in a
      predictive manner. In addition to enhancing the sensitivity of LFA, this
      universal concentration method could also be used to improve other detection
      assays.

PMID- 22847485
TI  - Specificity of effects of cognitive behavior therapy on coping, acceptance, and
      distress tolerance in a randomized controlled trial for smoking cessation.
AB  - OBJECTIVE: Although there is extensive evidence of the efficacy of cognitive
      behavioral therapy (CBT), it is less certain what potential mechanisms of change
      are specifically affected by CBT interventions. This study was intended to test
      the specific effects of CBT on compensatory coping skills, acceptance, and
      distress tolerance or persistence. METHOD: Using data from a randomized
      controlled trial of 8-session group CBT and a time-matched comparison condition
      for cigarette smokers, we evaluated CBT effects on compensatory coping skills,
      self-rated acceptance and behavioral markers of persistence and distress
      tolerance. Because depression proneness had moderated treatment response in the
      parent clinical trial (Kapson & Haaga, 2010), we tested not only main effects
      (CBT vs. comparison condition) but also moderated effects (treatment condition X
      depression proneness). RESULTS: CBT significantly improved compensatory coping
      skills only among the less depression-prone participants, who were the subset of
      smokers who did not benefit from CBT in terms of smoking cessation outcomes.
      There were no specific effects of CBT on acceptance or behavioral persistence.
      CONCLUSIONS: To the extent that CBT had specific effects on compensatory coping
      skills, it was for the participants who did not benefit clinically from the
      intervention. Much more theory-driven research on multiple candidate change
      mechanisms is needed to clarify how effective and specific treatments have their
      effects, for either patients in general or subsets of patients as in moderated
      effects.

PMID- 22847486
TI  - A low-molecular-weight supramolecular hydrogel of riboflavin bolaamphiphile for
      VEGF-siRNA delivery.
AB  - A low-molecular-weight hydrogel derived from riboflavin (vitamin B(2)) that self
      assembles to provide supramolecular nanofibers, biocompatible material, can be
      used to deliver VEGF-siRNA efficiently into human cells by the endocytosis
      pathway, where the siRNA is functionalized.

PMID- 22847487
TI  - Workdays lost due to occupational injuries among young workers in Brazil.
AB  - BACKGROUND: The severity of non-fatal work-related injuries has seldom been
      examined among young workers. We estimated the extent and distribution of
      workdays lost due to non-fatal work injuries using compensation data. METHODS:
      Data are from the Brazilian Institute of Social Insurance, for 2006. The study
      population is comprised of all insured workers of age 16-24. Descriptive
      statistics reflect workdays lost due to health-related disability, according to
      sex, age group, wage, and trade. RESULTS: Out of 4.8 million insured workers ages
      16-24 years, we estimated 1,282,940 workdays lost. We observed a larger number of
      median workdays lost among males age 20-24 in retail and service trades (83 days)
      and among 16-19-year-old females in the agriculture/fish/forestry/cattle (142
      days). CONCLUSIONS: Young workers experience a heavy burden of work-related
      injuries. Disability workdays may compromise school attendance and performance.
      Other potential impacts affect productivity and social insurance costs.

PMID- 22847488
TI  - Analysis of pulmonary dendritic cell maturation and migration during allergic
      airway inflammation.
AB  - Dendritic cells (DCs) are the key players involved in initiation of adaptive
      immune response by activating antigen-specific T cells. DCs are present in
      peripheral tissues in steady state; however in response to antigen stimulation,
      DCs take up the antigen and rapidly migrate to the draining lymph nodes where
      they initiate T cell response against the antigen. Additionally, DCs also play a
      key role in initiating autoimmune as well as allergic immune response. DCs play
      an essential role in both initiation of immune response and induction of
      tolerance in the setting of lung environment. Lung environment is largely
      tolerogenic, owing to the exposure to vast array of environmental antigens.
      However, in some individuals there is a break in tolerance, which leads to
      induction of allergy and asthma. In this study, we describe a strategy, which can
      be used to monitor airway DC maturation and migration in response to the antigen
      used for sensitization. The measurement of airway DC maturation and migration
      allows for assessment of the kinetics of immune response during airway allergic
      inflammation and also assists in understanding the magnitude of the subsequent
      immune response along with the underlying mechanisms. Our strategy is based on
      the use of ovalbumin as a sensitizing agent. Ovalbumin-induced allergic asthma is
      a widely used model to reproduce the airway eosinophilia, pulmonary inflammation
      and elevated IgE levels found during asthma. After sensitization, mice are
      challenged by intranasal delivery of FITC labeled ovalbumin, which allows for
      specific labeling of airway DCs which uptake ovalbumin. Next, using several DC
      specific markers, we can assess the maturation of these DCs and can also assess
      their migration to the draining lymph nodes by employing flow cytometry.

PMID- 22847489
TI  - A reliable and efficient first principles-based method for predicting pKa values.
      4. Organic bases.
AB  - The ionization (dissociation) constant (pK(a)) is one of the most important
      properties of a drug molecule. It is reported that almost 68% of ionized drugs
      are weak bases. To be able to predict accurately the pK(a) value(s) for a drug
      candidate is very important, especially in the early stages of drug discovery, as
      calculations are much cheaper than determining pK(a) values experimentally. In
      this study, we derive two linear fitting equations (pK(a) = a * DeltaE + b; where
      a and b are constants and DeltaE is the energy difference between the cationic
      and neutral forms, i.e., DeltaE = E(neutral) -E(cationic)) for predicting pK(a) s
      for organic bases in aqueous solution based on a training/test set of almost 500
      compounds using our previously developed protocol (OLYP/6-311+G**//3-21G(d) with
      the the conductor-like screening model solvation model, water as solvent; see
      Zhang, Baker, Pulay, J. Phys. Chem. A 2010, 114, 432). One equation is for
      saturated bases such as aliphatic and cyclic amines, anilines, guanidines,
      imines, and amidines; the other is for unsaturated bases such as heterocyclic
      aromatic bases and their derivatives. The mean absolute deviations for saturated
      and unsaturated bases were 0.45 and 0.52 pK(a) units, respectively. Over 60% and
      86% of the computed pK(a) values lie within +/-0.5 and +/-1.0 pK(a) units,
      respectively, of the corresponding experimental values. The results further
      demonstrate that our protocol is reliable and can accurately predict pK(a) values
      for organic bases.

PMID- 22847490
TI  - New insights into the mechanism of the Schiff base hydrolysis catalyzed by type I
      dehydroquinate dehydratase from S. enterica: a theoretical study.
AB  - The reaction pathway of Schiff base hydrolysis catalyzed by type I dehydroquinate
      dehydratase (DHQD) from S. enterica has been studied by performing molecular
      dynamics (MD) simulations and density functional theory (DFT) calculations and
      the corresponding potential energy profile has also been identified. On the basis
      of the results, the catalytic hydrolysis process for the wild-type enzyme
      consists of three major reaction steps, including nucleophilic attack on the
      carbon atom involved in the carbon-nitrogen double bond of the Schiff base
      intermediate by a water molecule, deprotonation of the His143 residue, and
      dissociation between the product and the Lys170 residue of the enzyme. The
      remarkable difference between this and the previously proposed reaction mechanism
      is that the second step here, absent in the previously proposed reaction
      mechanism, plays an important role in facilitating the reaction through a key
      proton transfer by the His143 residue, resulting in a lower energy barrier.
      Comparison with our recently reported results on the Schiff base formation and
      dehydration processes clearly shows that the Schiff base hydrolysis is rate
      determining in the overall reaction catalyzed by type I DHQD, consistent with the
      experimental prediction, and the calculated energy barrier of ~16.0 kcal mol(-1)
      is in good agreement with the experimentally derived activation free energy of
      ~14.3 kcal mol(-1). When the imidazole group of His143 residue is missing, the
      Schiff base hydrolysis is initiated by a hydroxide ion in the solution, rather
      than a water molecule, and both the reaction mechanism and the kinetics of Schiff
      base hydrolysis have been remarkably changed, clearly elucidating the catalytic
      role of the His143 residue in the reaction. The new mechanistic insights obtained
      here will be valuable for the rational design of high-activity inhibitors of type
      I DHQD as non-toxic antimicrobials, anti-fungals, and herbicides.

PMID- 22847491
TI  - Management of gastrointestinal stromal tumors: looking beyond the knife. An
      update on the role of adjuvant and neoadjuvant imatinib therapy.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) have traditionally been
      treated with surgical resection alone resulting in high rates of recurrence.
      However, the discovery of imatinib efficacy in GIST has revolutionized its
      management. DISCUSSION: Imatinib may be used as neoadjuvant therapy with the goal
      of reducing tumor size, minimizing surgical morbidity and, in some cases,
      rendering inoperable cases operable. In addition, imatinib use in the adjuvant
      setting to eradicate micrometastases and prevent recurrence has shown promising
      results in reducing relapse rates. Appropriate patient selection and optimal dose
      and duration of imatinib therapy remain undecided and require further
      investigation. We present a literature review and a case report of our patient
      with a symptomatic gastric GIST managed successfully utilizing neoadjuvant
      imatinib therapy, laparoscopic limited resection, and adjuvant imatinib therapy.

PMID- 22847492
TI  - Mouse forkhead L2 maintains repression of FSH-dependent genes in the granulosa
      cell.
AB  - The forkhead transcription factor forkhead box L2 (FOXL2) is expressed in
      granulosa cells of small and medium follicles in the mouse ovary. Foxl2 female
      knockout mice exhibit primordial follicle depletion and primary ovarian failure,
      but evidence from adult female conditional Foxl2 knockout mice suggests that
      FOXL2 may also play a significant role in maintenance of ovarian differentiation
      at stages beyond the primordial follicle and initial wave of folliculogenesis. We
      previously showed that human FOXL2 functions as a transcriptional repressor of
      several key genes involved in granulosa cell proliferation and differentiation,
      including steroidogenic acute regulatory protein (STAR), P450aromatase (CYP19A1
      (CYP19)), P450scc (CYP11A1 (CYP11A)), and cyclin D2 (CCND2). To elucidate the
      role of mouse FOXL2, we determined its role in transcriptional regulation in
      Chinese hamster ovary (CHO) cells and then confirmed our findings in mouse
      granulosa cells. We found that mouse FOXL2 represses the activities of the mouse
      Star, Cyp19a1, Cyp11a1 promoters in CHO cells, but may not repress the Ccnd2
      promoter, and identified the minimal mouse Star, Cyp19a1, and Cyp11a1 promoter
      regions responsive to FOXL2 regulation. We then knocked down Foxl2 in mouse
      granulosa cells using siRNA, which resulted in significantly increased expression
      levels of mouse Star, Cyp19a1, and Cyp11a1 but not Ccnd2. To increase Foxl2
      expression levels, we generated a mouse Foxl2 lentiviral construct and used it to
      infect mouse granulosa cells. Following lentiviral infection, the expression
      levels of mouse Star, Cyp19a1, and Cyp11a1, but not Ccnd2, decreased
      significantly. These data confirm that mouse FOXL2 functions as a transcriptional
      repressor of key granulosa cell genes that influence ovarian development.

PMID- 22847493
TI  - Transforming between discrete and continuous angle distribution models:
      application to protein chi1 torsions.
AB  - Two commonly employed angular-mobility models for describing amino-acid side
      chain chi(1) torsion conformation, the staggered-rotamer jump and the normal
      probability density, are discussed and performance differences in applications to
      scalar-coupling data interpretation highlighted. Both models differ in their
      distinct statistical concepts, representing discrete and continuous angle
      distributions, respectively. Circular statistics, introduced for describing
      torsion-angle distributions by using a universal circular order parameter central
      to all models, suggest another distribution of the continuous class, here
      referred to as the elliptic model. Characteristic of the elliptic model is that
      order parameter and circular variance form complementary moduli. Transformations
      between the parameter sets that describe the probability density functions
      underlying the different models are provided. Numerical aspects of parameter
      optimization are considered. The issues are typified by using a set of chi(1)
      related (3) J coupling constants available for FK506-binding protein. The
      discrete staggered-rotamer model is found generally to produce lower order
      parameters, implying elevated rotatory variability in the amino-acid side chains,
      whereas continuous models tend to give higher order parameters that suggest
      comparatively less variation in angle conformations. The differences perceived
      regarding angular mobility are attributed to conceptually different features
      inherent to the models.

PMID- 22847494
TI  - Roles of ceramide and sphingolipids in pancreatic beta-cell function and
      dysfunction.
AB  - Recent technical advances have re-invigorated the study of sphingolipid
      metabolism in general, and helped to highlight the varied and important roles
      that sphingolipids play in pancreatic beta-cells. Sphingolipid metabolites such
      as ceramide, glycosphingolipids, sphingosine 1-phosphate and gangliosides
      modulate many beta-cell signaling pathways and processes implicated in beta-cell
      diabetic disease such as apoptosis, beta-cell cytokine secretion, ER-to-golgi
      vesicular trafficking, islet autoimmunity and insulin gene expression. They are
      particularly relevant to lipotoxicity. Moreover, the de novo synthesis of
      sphingolipids occurs on many subcellular membranes, in parallel to secretory
      vesicle formation, traffic and granule maturation events. Indeed, the composition
      of the plasma membrane, determined by the activity of neutral sphingomyelinases,
      affects beta-cell excitability and potentially insulin exocytosis while another
      glycosphingolipid, sulfatide, determines the stability of insulin crystals in
      granules. Most importantly, sphingolipid metabolism on internal membranes is also
      strongly implicated in regulating beta-cell apoptosis.

PMID- 22847496
TI  - Metabolomic analysis of pancreatic beta-cell insulin release in response to
      glucose.
AB  - Defining the key metabolic pathways that are important for fuel-regulated insulin
      secretion is critical to providing a complete picture of how nutrients regulate
      insulin secretion. We have performed a detailed metabolomics study of the clonal
      beta-cell line 832/13 using a gas chromatography-mass spectrometer (GC-MS) to
      investigate potential coupling factors that link metabolic pathways to insulin
      secretion. Mid-polar and polar metabolites, extracted from the 832/13 beta-cells,
      were derivatized and then run on a GC/MS to identify and quantify metabolite
      concentrations. Three hundred fifty-five out of 527 chromatographic peaks could
      be identified as metabolites by our metabolomic platform. These identified
      metabolites allowed us to perform a systematic analysis of key pathways involved
      in glucose-stimulated insulin secretion (GSIS). Of these metabolites, 41 were
      consistently identified as biomarker for GSIS by orthogonal partial least-squares
      (OPLS). Most of the identified metabolites are from common metabolic pathways
      including glycolytic, sorbitol-aldose reductase pathway, pentose phosphate
      pathway, and the TCA cycle suggesting these pathways play an important role in
      GSIS. Lipids and related products were also shown to contribute to the clustering
      of high glucose sample groups. Amino acids lysine, tyrosine, alanine and serine
      were upregulated by glucose whereas aspartic acid was downregulated by glucose
      suggesting these amino acids might play a key role in GSIS. In summary, a
      coordinated signaling cascade elicited by glucose metabolism in pancreatic beta
      cells is revealed by our metabolomics platform providing a new conceptual
      framework for future research and/or drug discovery.

PMID- 22847495
TI  - alpha-cell role in beta-cell generation and regeneration.
AB  - This review considers the role of alpha-cells in beta-cell generation and
      regeneration. We present recent evidence obtained from lineage-tracing studies
      showing that alpha-cells can serve as progenitors of beta-cells and present a
      hypothetical model how injured beta-cells might activate alpha-cells in adult
      islets to promote beta-cell regeneration. beta-cells appear to arise by way of
      their trans-differentiation from undifferentiated alpha progenitor cells, pro
      alpha-cells, both during embryonic development of the islets and in the adult
      pancreas in response to beta-cell injuries. Plasticity of alpha-cells is endowed
      by the expression of the gene encoding proglucagon, a prohormone that can give
      rise to glucagon and glucagon-like peptides (GLPs). The production of glucagon
      from proglucagon is characteristic of fully-differentiated alpha-cells whereas
      GLP-1 is a product of undifferentiated alpha-cells. GLP-1, a cell growth and
      survival factor, is proposed to promote the expansion of neurogenin3-expressing,
      undifferentiated pro-alpha-cells during development. beta-cells arise from pro
      alpha-cells by a change in the relative amounts of the transcription factors Arx
      and Pax4, master regulators of the alpha- and beta-cell lineages, respectively. A
      paracrine/autocrine model is proposed whereby injuries of beta-cells in adult
      islets induce the production and release of factors, such as stromal cell-derived
      factor-1, that cause the de-differentiation of adjacent alpha-cells into pro
      alpha-cells. Pro-alpha-cells produce GLP-1 and its receptor that renders them
      competent to trans-differentiate into beta-cells. The trans-differentiation of
      pro-alpha-cells into beta-cells provides a potentially exploitable mechanism for
      the regeneration of beta-cells in individuals with type 1 diabetes.

PMID- 22847498
TI  - Thrombopoietin receptor agonists in the treatment of immune thrombocytopenia: a
      clinician's perspective.

PMID- 22847497
TI  - Islet amyloid polypeptide in pancreatic islets from type 2 diabetic subjects.
AB  - AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a chief constituent of
      amyloid deposits in pancreatic islets, characteristic histopathology for type 2
      diabetes. The goal of this study was to analyze islet cell composition in
      diabetic islets for the process of transforming water-soluble IAPP in beta-cells
      to water-insoluble amyloid deposits by Immunocytochemical staining using
      different dilutions of anti-IAPP antibody. IAPP in beta-cell granules may
      initiate beta-cell necrosis through apoptosis to form interstitial amyloid
      deposits in type 2 diabetic islets. RESULTS: Control islets revealed twice as
      much beta-cells as alpha-cells whereas 15 of 18 type 2 diabetic cases (83%)
      revealed alpha- cells as major cells in larger islets. Diabetic islets consisted
      of more larger islets with more sigma-cells than beta-cells, which contribute to
      hyperglucagonemia. In control islets, percentage of IAPP-positive cells against
      beta-cells was 40-50% whereas percentage for type 2 diabetic islets was about
      25%. Amyloid deposits in diabetic islets were not readily immunostained for IAPP
      using 1: 800 diluted antibody, however, 1: 400 and 1: 200 diluted solutions
      provided stronger immunostaining in early stages of islet amyloidogenesis after
      treating the deparaffinized sections with formic acid. METHODS: Using
      commercially available rabbit antihuman IAPP antibody, immunocytochemical
      staining was performed on 18 cases of pancreatic tissues from type 2 diabetic
      subjects by systematically immunostaining for insulin, glucagon, somatostatin
      (SRIF) and IAPP compared with controls. Sizes of islets were measured by 1 cm
      scale, mounted in 10X eye piece. CONCLUSIONS/INTERPRETATION: alpha cells were
      major islet cells in majority of diabetic pancreas (83%) and all diabetic islets
      contained less IAPP-positive cells than controls, indicating that IAPP deficiency
      in pancreatic islets is responsible for decreased IAPP in blood. In diabetic
      islets, water-soluble IAPP disappeared in beta-cell granules, which transformed
      to water-insoluble amyloid deposits. Amyloid deposits were not readily
      immunostained using IAPP 1: 800 diluted antibody but were stronger immunostained
      for IAPP in early stages of amyloid deposited islets using less diluted solutions
      after formic acid treatment. In early islet amyloidogenesis, dying beta-cell
      cytoplasm was adjacently located to fine amyloid fibrils, supporting that IAPP in
      secretary granules from dying beta cells served as nidus for islet beta-sheet
      formation.

PMID- 22847499
TI  - Differential effects of thyroid status on regional H2O2 production in slow- and
      fast-twitch muscle of ducklings.
AB  - Birds seem to employ powerful physiological strategies to curb the harmful
      effects of reactive oxygen species (ROS) because they generally live longer than
      predicted by the free radical theory of aging. However, little is known about the
      physiological mechanisms that confer protection to birds against excessive ROS
      generation. Hence, we investigated the ability of birds to control mitochondrial
      ROS generation during physiologically stressful periods. In our study, we
      analyzed the relationship between the thyroid status and the function of
      intermyofibrillar and subsarcolemmal mitochondria located in glycolytic and
      oxidative muscles of ducklings. We found that the intermyofibrillar mitochondria
      of both glycolytic and oxidative muscles down regulate ROS production when plasma
      T3 levels rise. The intermyofibrillar mitochondria of the gastrocnemius muscle
      (an oxidative muscle) produced less ROS and were more sensitive than the
      pectoralis muscle (a glycolytic muscle) to changes in plasma T3. Such differences
      in the ROS production by glycolytic and oxidative muscles were associated with
      differences in the membrane proton permeability and in the rate of free radical
      leakage within the respiratory chain. This is the first evidence which shows that
      in birds, the amount of ROS that the mitochondria release is dependent on: (1)
      their location within the muscle; (2) the type of muscle (glycolytic or
      oxidative) and (3) on the thyroid status. Reducing muscle mitochondrial ROS
      generation might be an important mechanism in birds to limit oxidative damage
      during periods of physiological stress.

PMID- 22847500
TI  - Body regional distribution and stratification of fatty acids in the blubber of
      New Zealand sea lions: implications for diet predictions.
AB  - Fatty acids (FAs) from blubber are often analysed to assess the diet of marine
      mammals. However, distribution of blubber FAs is not necessarily uniform along
      the body. It is therefore important to understand the deposition of dietary fat
      to be able to estimate the diet. We analysed the FA compositions of the thoracic
      ventral (T region) blubber of 28 New Zealand (NZ) sea lions Phocarctos hookeri by
      caught by the southern arrow squid Nototodarus sloani fishery. Each blubber
      sample was divided into an inner and an outer layer. For 16 of these 28 animals,
      the pelvic dorsal (P) region was also sampled. The influence of body region and
      layer was statistically tested on the distribution of blubber FAs. We found
      minimal differences between the P and T regions (3 out of 29 FAs). The outer
      blubber layer was more concentrated in short-chain monounsaturated FAs, and less
      concentrated in saturated FAs, but the degree of stratification was small. Diet
      predictions from quantitative FA signature analysis (QFASA) applied on different
      body regions were similar. When applied to different blubber layers, QFASA gave
      some variation in the contribution of rattails (~25 % in outer blubber vs. ~12 %
      in inner blubber). Nonetheless, diet predicted from both layers was dominated by
      similar prey species: octopus, hoki and rattails. Hoki and rattails shared a
      similar ecological niche. Therefore, feeding ecology of NZ sea lions inferred
      from the inner or the outer blubber would lead to the same conclusions. In the
      case of NZ sea lions, the outer layer of blubber, if the only sample accessible,
      could be a useful tissue for diet inference from FAs.

PMID- 22847502
TI  - Adjuvant chemotherapy benefits older and younger non-small cell lung cancer
      patients alike.

PMID- 22847503
TI  - Surface cross-linked UHMWPE can enable the use of larger femoral heads in total
      joints.
AB  - Limiting cross-linking to the articular surfaces of ultrahigh molecular weight
      polyethylene (UHMWPE) to increase wear resistance while preventing detrimental
      effects of cross-linking on mechanical strength has been a desirable goal. A
      surface cross-linked UHMWPE can be achieved by blending UHMWPE with a free
      radical scavenger, such as vitamin E, consolidating the blend into an implant
      shape, extracting the vitamin E from the surface, and radiation cross-linking the
      surface extracted blend. This process results in high cross-link density in the
      vitamin E-depleted surface region because vitamin E hinders cross-linking during
      irradiation. In this study, we described the properties of successful extraction
      media and the manipulation of the wear and mechanical properties of extracted,
      irradiated blends. We showed that these formulations could have similar wear and
      significantly improved mechanical properties compared to currently available
      highly cross-linked UHMWPEs. We believe that these materials can enable thinner
      implant forms and more anatomical designs in joint arthroplasty and may provide a
      feasible alternative to metal-on-metal implants.

PMID- 22847501
TI  - Determinants of intra-specific variation in basal metabolic rate.
AB  - Basal metabolic rate (BMR) provides a widely accepted benchmark of metabolic
      expenditure for endotherms under laboratory and natural conditions. While most
      studies examining BMR have concentrated on inter-specific variation, relatively
      less attention has been paid to the determinants of within-species variation.
      Even fewer studies have analysed the determinants of within-species BMR variation
      corrected for the strong influence of body mass by appropriate means (e.g.
      ANCOVA). Here, we review recent advancements in studies on the quantitative
      genetics of BMR and organ mass variation, along with their molecular genetics.
      Next, we decompose BMR variation at the organ, tissue and molecular level. We
      conclude that within-species variation in BMR and its components have a clear
      genetic signature, and are functionally linked to key metabolic process at all
      levels of biological organization. We highlight the need to integrate molecular
      genetics with conventional metabolic field studies to reveal the adaptive
      significance of metabolic variation. Since comparing gene expressions inter
      specifically is problematic, within-species studies are more likely to inform us
      about the genetic underpinnings of BMR. We also urge for better integration of
      animal and medical research on BMR; the latter is quickly advancing thanks to the
      application of imaging technologies and 'omics' studies. We also suggest that
      much insight on the biochemical and molecular underpinnings of BMR variation can
      be gained from integrating studies on the mammalian target of rapamycin (mTOR),
      which appears to be the major regulatory pathway influencing the key molecular
      components of BMR.

PMID- 22847511
TI  - Metformin and breast cancer risk: a meta-analysis and critical literature review.
AB  - Observational studies have suggested that metformin decreases the incidence of
      several common cancers. However, findings regarding breast cancer have been
      mixed. In order to explore this issue, a systematic literature review and meta
      analysis were performed with a focus on potential biases. We conducted a
      comprehensive literature search for all pertinent studies addressing metformin
      use and breast cancer risk by searching PubMed, Cochrane Library, and Scopus
      (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or
      "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms."
      When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most
      adjusted estimate was used in the base-case analysis. We pooled the adjusted HR
      and performed sensitivity analyses on duration of metformin use (> or <=3 years
      use), study quality (assessed using the GRADE system), and initial observation
      year of the cohort (before vs after 1997). From a total of 443 citations, 18 full
      text articles were considered, and seven independent studies were included. All
      were observational (four cohort and three case control). Our combined OR of all
      seven studies was 0.83 (0.71-0.97). Stronger associations were found when
      analyses were limited to studies estimating the impact of longer metformin use
      (OR = 0.75. 95 % CI 0.62, 0.91) or among studies that began observing their
      cohort before 1997 (OR = 0.68. 95 % CI 0.55-0.084). Stratification according to
      study quality did not affect the combined OR but higher quality studies had
      smaller CI and achieved statistical significance. Interpretation is limited by
      the observational nature of reports and different comparison groups. Our analyses
      support a protective effect of metformin on breast cancer risk among
      postmenopausal women with diabetes. Clinical trials are needed for definitive
      determination of the role of metformin in breast cancer risk reduction.

PMID- 22847512
TI  - Low TLR9 expression defines an aggressive subtype of triple-negative breast
      cancer.
AB  - Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers.
      Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of
      TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9
      expression is associated with significantly shortened disease-specific survival
      in patients with triple negative but not with ER+ breast cancers. A likely
      mechanism of this clinical finding involves differential responses to hypoxia.
      Our pre-clinical studies indicate that while TLR9 expression is hypoxia
      regulated, low TLR9 expression has different effects on triple negative and ER+
      breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9
      siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly
      due to differential TLR9-regulated TIMP-3 expression, which remains detectable in
      ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our
      results demonstrate a novel role for this innate immunity receptor in cancer
      biology and suggest that TLR9 expression may be a novel marker for triple
      negative breast cancer patients who are at a high risk of relapse. Furthermore,
      these results suggest that interventions or events, which induce hypoxia or down
      regulate TLR9 expression in triple-negative breast cancer cells may actually
      induce their spread.

PMID- 22847513
TI  - Gold nanoparticles prepared by glycinate ionic liquid assisted multi-photon
      photoreduction.
AB  - We have successfully prepared gold nanoparticles (AuNPs) with flower-like and
      spherical morphology through multi-photon photoreduction (MPR) of an aqueous
      solution of HAuCl(4) and (2-hydroxyethyl) trimethylammonium glycinate
      ([HETMA][Gly]) ionic liquid (IL) through the use of a femtosecond laser. The
      results of (1)H NMR and UV-Vis absorption indicated that AuNPs were produced from
      the photoreduction of the [Gly]-Au(iii) complex. Spherical AuNPs of about 2.5 nm
      were obtained on the solution when irradiated for 2 h, then aggregated into
      flower-like AuNPs of several tens of nanometers assisted by the IL with an
      increase in the irradiation time. Furthermore, precipitates of spherical AuNPs
      with the size of around 15 nm were formed after being irradiated for 6 h. The
      mechanisms of the MPR reaction and controlled growth of AuNPs have also been
      discussed.

PMID- 22847514
TI  - Global expression profiling of globose basal cells and neurogenic progression
      within the olfactory epithelium.
AB  - Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory
      epithelium in the face of piecemeal neuronal turnover and restores it following
      wholesale loss. The molecular phenotypes corresponding to different stages along
      the progression from multipotent globose basal cell (GBC) progenitor to
      differentiated olfactory sensory neuron are poorly characterized. We used the
      transgenic expression of enhanced green fluorescent protein (eGFP) and cell
      surface markers to FACS-isolate DeltaSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and
      immature neurons, and DeltaOMP-eGFP(+) mature neurons from normal adult mice. In
      addition, the latter two populations were also collected 3 weeks after olfactory
      bulb ablation, a lesion that results in persistently elevated neurogenesis.
      Global profiling of mRNA from the populations indicates that all stages of
      neurogenesis share a cohort of >2,100 genes that are upregulated compared to
      sustentacular cells. A further cohort of >1,200 genes are specifically
      upregulated in GBCs as compared to sustentacular cells and differentiated
      neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had
      little effect on the transcriptional profile of the Neurog1-eGFP(+) population.
      In contrast, the abbreviated lifespan of DeltaOMP-eGFP(+) neurons born in the
      absence of the bulb correlated with substantial differences in gene expression as
      compared to the mature neurons of the normal epithelium. Detailed examination of
      the specific genes upregulated in the different progenitor populations revealed
      that the chromatin modifying complex proteins LSD1 and coREST were expressed
      sequentially in upstream DeltaSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature
      neurons. The expression patterns of these proteins are dynamically regulated
      after activation of the epithelium by methyl bromide lesion.

PMID- 22847515
TI  - Computed tomography-guided time-domain diffuse fluorescence tomography in small
      animals for localization of cancer biomarkers.
AB  - Small animal fluorescence molecular imaging (FMI) can be a powerful tool for
      preclinical drug discovery and development studies. However, light absorption by
      tissue chromophores (e.g., hemoglobin, water, lipids, melanin) typically limits
      optical signal propagation through thicknesses larger than a few millimeters.
      Compared to other visible wavelengths, tissue absorption for red and near
      infrared (near-IR) light absorption dramatically decreases and non-elastic
      scattering becomes the dominant light-tissue interaction mechanism. The
      relatively recent development of fluorescent agents that absorb and emit light in
      the near-IR range (600-1000 nm), has driven the development of imaging systems
      and light propagation models that can achieve whole body three-dimensional
      imaging in small animals. Despite great strides in this area, the ill-posed
      nature of diffuse fluorescence tomography remains a significant problem for the
      stability, contrast recovery and spatial resolution of image reconstruction
      techniques and the optimal approach to FMI in small animals has yet to be agreed
      on. The majority of research groups have invested in charge-coupled device (CCD)
      based systems that provide abundant tissue-sampling but suboptimal sensitivity,
      while our group and a few others have pursued systems based on very high
      sensitivity detectors, that at this time allow dense tissue sampling to be
      achieved only at the cost of low imaging throughput. Here we demonstrate the
      methodology for applying single-photon detection technology in a fluorescence
      tomography system to localize a cancerous brain lesion in a mouse model. The
      fluorescence tomography (FT) system employed single photon counting using
      photomultiplier tubes (PMT) and information-rich time-domain light detection in a
      non-contact conformation. This provides a simultaneous collection of transmitted
      excitation and emission light, and includes automatic fluorescence excitation
      exposure control, laser referencing, and co-registration with a small animal
      computed tomography (microCT) system. A nude mouse model was used for imaging.
      The animal was inoculated orthotopically with a human glioma cell line (U251) in
      the left cerebral hemisphere and imaged 2 weeks later. The tumor was made to
      fluoresce by injecting a fluorescent tracer, IRDye 800CW-EGF (LI-COR Biosciences,
      Lincoln, NE) targeted to epidermal growth factor receptor, a cell membrane
      protein known to be overexpressed in the U251 tumor line and many other cancers.
      A second, untargeted fluorescent tracer, Alexa Fluor 647 (Life Technologies,
      Grand Island, NY) was also injected to account for non-receptor mediated effects
      on the uptake of the targeted tracers to provide a means of quantifying tracer
      binding and receptor availability/density. A CT-guided, time-domain algorithm was
      used to reconstruct the location of both fluorescent tracers (i.e., the location
      of the tumor) in the mouse brain and their ability to localize the tumor was
      verified by contrast-enhanced magnetic resonance imaging. Though demonstrated for
      fluorescence imaging in a glioma mouse model, the methodology presented in this
      video can be extended to different tumor models in various small animal models
      potentially up to the size of a rat.

PMID- 22847516
TI  - Upper body musculoskeletal symptoms of Latino poultry processing workers and a
      comparison group of Latino manual workers.
AB  - BACKGROUND: Upper body musculoskeletal injuries are often attributed to rapid
      work pace and repetitive motions. These job features are common in poultry
      processing, an industry that relies on Latino immigrants. Few studies document
      the symptom burden of immigrant Latinos employed in poultry processing or other
      manual jobs. METHODS: Latino poultry processing workers (n = 403) and a
      comparison population of 339 Latino manual workers reported symptoms for six
      upper body sites during interviews. We tabulated symptoms and explored factors
      associated with symptom counts. RESULTS: Back symptoms and wrist/hand symptoms
      lasting more than 1-day were reported by over 35% of workers. Poultry processing
      workers reported more symptoms than comparison workers, especially wrist and
      elbow symptoms. The number of sites at which workers reported symptoms was
      elevated for overtime workers and workers who spoke an indigenous language during
      childhood. CONCLUSION: Workplace conditions facing poultry processing and
      indigenous language speaking workers deserve further exploration.

PMID- 22847517
TI  - Are there biologic differences between male and female breast cancer explaining
      inferior outcome of men despite equal stage and treatment?!
AB  - BACKGROUND: Reasons for inferior outcome of male compared to female breast cancer
      are still under debate. Therefore, we retrospectively analyzed male breast cancer
      cases to figure out possible treatment- and gender-related differences. PATIENTS
      AND METHODS: A total of 40 men (median age 62 years) were curatively treated with
      mastectomy and postoperative radiotherapy from 1982-2007. They presented
      predominantly in stages II and IIIb. Postoperative radiotherapy was applied with
      doses of 1.8-2.5 Gy to a median of 50 Gy including regional lymphatics in 22
      patients. Adjuvant systemic treatment consisted of chemotherapy (22.5%) and
      antihormonal treatment (55%). For reasons of comparison, we estimated outcome of
      a virtual female matched cohort for no/equal to men/optimal adjuvant treatment
      with the Adjuvant!Online((r)) 8.0 algorithm. RESULTS: After a median follow-up of
      47 months, the estimated 5-year local control rate was 97%, disease-free and
      distant metastasis-free survival rates reached 79% and 82%, respectively. With
      update of survival data by tumor registry, mean overall survival reached 120
      months with 5- and 10-year overall survival rates of 66% and 43%, respectively.
      Predominant prognostic factor was T-stage for overall survival (T1/2 vs. T4: >
      80% vs. 30%). The generated virtual matched cohorts of women with equal
      characteristics reached superior 10-year-overall survival for no/equal to
      men/optimal adjuvant treatment with 55/59/68%. CONCLUSION: Compared to historical
      and virtual matched cohorts of women, male breast cancer patients had inferior
      outcome despite of equal stage and treatment which indicates that biological
      differences (of tumor or population) may contribute to worse prognosis.

PMID- 22847518
TI  - [Evaluation of time, attendance of medical staff, and resources during
      stereotactic radiotherapy/radiosurgery : QUIRO-DEGRO Trial].
AB  - BACKGROUND: The German Society of Radiation Oncology ("Deutsche Gesellschaft fur
      Radioonkologie", DEGRO) initiated a multicenter trial to develop and evaluate
      adequate modules to assert core processes and subprocesses in radiotherapy. The
      aim of this prospective evaluation was to methodical assess the required
      resources (technical equipment and medical staff) for stereotactic
      radiotherapy/radiosurgery. MATERIAL AND METHODS: At two radiotherapy centers of
      excellence (University Hospitals of Heidelberg and Marburg/Giessen), the manpower
      and time required for the implementation of intra- and extracranial stereotactic
      radiotherapy was prospectively collected consistently over a 3-month period. The
      data were collected using specifically developed process acquisition tools and
      standard forms and were evaluated using specific process analysis tools. RESULTS:
      For intracranial (extracranial) fractionated stereotactic radiotherapy (FSRT) and
      radiosurgery (RS), a total of 1,925 (270) and 199 (36) records, respectively,
      could be evaluated. The approximate time needed to customize the immobilization
      device was median 37 min (89 min) for FRST and 31 min (26 min) for RS, for the
      contrast enhanced planning studies 22 and 27 min (25 and 28 min), for physical
      treatment planning 122 and 59 min (187 and 27 min), for the first and routine
      radiotherapy sessions for FSRT 40 and 13 min (58 and 31 min), respectively. The
      median time needed for the RS session was 58 min (45 min). The corresponding
      minimal manpower needed was 2 technicians for customization of the immobilization
      device, 2.5 technicians and 1 consultant for the contrast-enhanced planning
      studies, 1 consultant, 0.5 resident and 0.67 medical physics expert (MPE) for
      physical treatment planning, as well as 1 consultant, 0.5 resident, and 2.5
      technicians for the first radiotherapy treatment and 2.33 technicians for routine
      radiotherapy sessions. CONCLUSION: For the first time, the resource requirements
      for a radiotherapy department for the maintenance, protection and optimization of
      operational readiness for the application of intra- and extracranial stereotactic
      radiotherapy was determined methodically.

PMID- 22847520
TI  - [Conventional versus hypofractionated intensity-modulated radiotherapy for
      prostate cancer].

PMID- 22847519
TI  - [Prognostic significance of changes of tumor epidermal growth factor receptor
      expression after neoadjuvant chemoradiation in patients with rectal
      adenocarcinoma].
AB  - PURPOSE: The aim of the present study was to examine the effect of neoadjuvant
      chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in
      patients with locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: A
      total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were
      studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external
      radiation with concomitant continuous 5-fluorouracil. Surgical resection was
      performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment
      biopsies and in the resected specimens was assessed with immunohistochemistry.
      RESULTS: Patients with an increase of EGFR expression during chemoradiation had
      significantly shorter disease-free survival (DFS; p = 0.003) and overall survival
      (OS; p = 0.005) compared to patients with either no change or decrease in EGFR
      expression. The 5-year DFS in patients with increased EGFR expression was only
      29% compared to 61% in patients without an increase of EGFR expression.
      Similarly, the 5-year OS of the patients with increased EGFR expression was 29%
      compared to 66% in patients without an increase of EGFR expression. All
      recurrences in patients who had an increase of EGFR expression occurred within
      the first 2 years after the treatment. The increase in EGFR expression was the
      only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using
      multivariate Cox regression analysis. CONCLUSION: An increase of EGFR expression
      during chemoradiation may be associated with significantly shorter DFS and OS.
      The increase of EGFR could identify a population of patients in whom the effect
      of the treatment with anti-EGFR therapy should be studied.

PMID- 22847521
TI  - Efficient sampling of protein conformational space using fast loop building and
      batch minimization on highly parallel computers.
AB  - All-atom sampling is a critical and compute-intensive end stage to protein
      structural modeling. Because of the vast size and extreme ruggedness of
      conformational space, even close to the native structure, the high-resolution
      sampling problem is almost as difficult as predicting the rough fold of a
      protein. Here, we present a combination of new algorithms that considerably speed
      up the exploration of very rugged conformational landscapes and are capable of
      finding heretofore hidden low-energy states. The algorithm is based on a
      hierarchical workflow and can be parallelized on supercomputers with up to
      128,000 compute cores with near perfect efficiency. Such scaling behavior is
      notable, as with Moore's law continuing only in the number of cores per chip,
      parallelizability is a critical property of new algorithms. Using the enhanced
      sampling power, we have uncovered previously invisible deficiencies in the
      Rosetta force field and created an extensive decoy training set for optimizing
      and testing force fields.

PMID- 22847522
TI  - Gibbons (Hylobates pileatus, H. moloch, H. lar, Symphalangus syndactylus) follow
      human gaze, but do not take the visual perspective of others.
AB  - We investigated four gibbon species of two different genera (Hylobates pileatus,
      H. moloch, H. lar, Symphalangus syndactylus) in terms of their looking behavior
      in response to a human who either looked up or looked at the gibbon. Comparing
      those two conditions, gibbons as a group looked up more when the human was
      looking up, but they also performed more looks in other directions and thus
      generally looked more in this condition. Unlike great apes, gibbons did not
      respond differently between conditions when only the first look on every trial
      was considered. Furthermore, they did not perform double looks up to check where
      the human was looking and also did not habituate to the human's looks up. This
      suggests that gibbons co-orient with human gaze, but unlike great apes, they do
      not take the visual perspective of others.

PMID- 22847523
TI  - Reliability and comparability of the accelerometer and the linear position
      measuring device in resistance training.
AB  - The purpose of this study was to determine the intermachine reliability attained
      from devices used to measure the common variables in sports performance.
      Repeatability conditions were established by creating a similar set of conditions
      under which the measurements were taken from both devices. The objectives of this
      research were to demonstrate the reliability between two devices in a bench press
      movement--the linear position measuring device (LPM) isoinertial dynamometer (T
      Force) and the 3D (Myotest) accelerometer (AC)--and to compare the existing
      correlations between maximum velocity, maximum estimated strength, and peak power
      estimate variables in the bench press exercise. Forty bench press exercise trials
      were analyzed simultaneously, performed by 3 different subjects (age: 26.74 +/-
      1.2 years, height: 175.74 +/- 4.04 cm, weight: 78.7 +/- 3.35 kg) at maximum
      velocity (25 kg additional load). Three simple linear regression models were
      developed, supplied by the LPM on the basis of the AC data. The assumption of
      independence of errors was compared by means of the Durban-Watson test, and
      partial autocorrelation coefficients were established at an overall p < 0.05
      significance level. It has not been possible to confirm the presence of a general
      correlation between the measurements of both devices. Regarding the assumption of
      independence of errors, the presence of generalized autocorrelation was
      confirmed. Linear regression analysis revealed an intermachine correlation in one
      of the nonconclusive cases, (peak power) variable and subject 1, r (10) = 0.640,
      p = 0.024. No partial autocorrelation was found. The devices should not be used
      interchangeably as instruments.

PMID- 22847524
TI  - Changes in muscle architecture and performance during a competitive season in
      female softball players.
AB  - The purpose of this research was (a) to examine the performance changes that
      occur in elite female softball players during 20 weeks of softball training (that
      included 14 weeks of periodized resistance training [RT]) and (b) to examine the
      relationship between percent change (%change) in muscle architecture variables
      and %change in strength, speed, and change of direction performance. Ten female
      softball players (age = 18.1 +/- 1.6 years, height = 166.5 +/- 8.9 cm, weight =
      72.4 +/- 10.8 kg) from a state Australian Institute of Sport softball team were
      tested for maximal lower-body strength using a 3 repetition maximum for a
      predicted 1 repetition maximum (1RM) and peak force, peak velocity (PV), and peak
      power (PP) were measured during jump squats (JS) unloaded and loaded. In
      addition, the first base (1B) and the second base (2B) sprint performance, change
      of direction (505) on dominant (D) and nondominant (ND) sides, aerobic capacity,
      and muscle architecture characteristics of vastus lateralis (VL) including muscle
      thickness (MT), fascicle length (FL), and pennation angle (thetap) were examined.
      The testing sessions occurred pre, mid, and post training (total 20 week pre- and
      in-season training period). Changes over time were analyzed by repeated-measures
      analysis of variance. The relationship between %change in muscle architecture
      variables and strength, speed, and change of direction variables from pre to post
      were assessed by Pearson product-moment correlation coefficient. Significant
      improvements in PV and PP occurred at all JS loads pre- to mid-testing and pre-
      to post-testing. Significant increases occurred pre-post in absolute 1RM,
      relative 1RM, 505 ND, and 2B sprint. The strongest relationships were found
      between %change in VL MT and 1B sprint (r = -0.80, p = 0.06), %change in VL FL
      and 2B sprint (r = -0.835, p = 0.02), and %change in relative 1RM and 505 D (r = 
      0.70, p = 0.04). In conclusion, gains in strength, power, and performance can
      occur during the season in elite softball players who are also engaged in a
      periodized RT program. Furthermore, changes in performance measures are
      associated with changes in muscle architecture.

PMID- 22847525
TI  - Linear and star-shaped pyrazine-containing acene dicarboximides with high
      electron-affinity.
AB  - A series of linear and star-shaped pyrazine-containing acene molecules 1a-b, 2a-b
      and 3 substituted by dicarboximide groups are synthesized via condensation
      reactions between o-diamine and dione. High electron affinity (up to 4.01 eV) is
      achieved due to the introduction of an electron-deficient pyrazine moiety and the
      attachment of electron-withdrawing dicarboximide groups. Some of these molecules
      show thermal liquid crystalline behavior and their space-charge limited current
      mobilities are measured. The high electron affinity and liquid crystalline
      property qualify them as promising electron transporting materials in organic
      optoelectronic devices.

PMID- 22847526
TI  - Platelet count or bleeding as the outcome in ITP trials?

PMID- 22847527
TI  - Three-dimensional skeletonization and symbolic description in vascular imaging:
      preliminary results.
AB  - OBJECTIVE: A general method was developed to analyze and describe tree-like
      structures needed for evaluation of complex morphology, such as the cerebral
      vascular tree. Clinical application of the method in neurosurgery includes
      planning of the surgeon's intraoperative gestures. METHOD: We have developed a 3D
      skeletonization method adapted to tubular forms with symbolic description. This
      approach implements an iterative Dijkstra minimum cost spanning tree, allowing a
      branch-by-branch skeleton extraction. The proposed method was implemented using
      the laboratory software platform (ArtiMed). The 3D skeleton approach was tested
      on simulated data and preliminary trials on clinical datasets mainly based on
      magnetic resonance image acquisitions. RESULTS: A specific experimental
      evaluation plan was designed to test the skeletonization and symbolic description
      methods. Accuracy was tested by calculating the positioning error, and robustness
      was verified by comparing the results on a series of 18 rotations of the initial
      volume. Accuracy evaluation showed a Haussdorff's distance always smaller than 17
      voxels and Dice's similarity coefficient greater than 70 %. CONCLUSION: Our
      method of symbolic description enables the analysis and interpretation of a
      vascular network obtained from angiographic images. The method provides a
      simplified representation of the network in the form of a skeleton, as well as a
      description of the corresponding information in a tree-like view.

PMID- 22847528
TI  - Left ventricle wall motion quantification from echocardiographic images by non
      rigid image registration.
AB  - PURPOSE: The aim of this study is to evaluate the efficiency of applying a new
      non-rigid image registration method on two-dimensional echocardiographic images
      for computing the left ventricle (LV) myocardial motion field over a cardiac
      cycle. METHODS: The key feature of our method is to register all images in the
      sequence to a reference image (end-diastole image) using a hierarchical
      transformation model, which is a combination of an affine transformation for
      modeling the global LV motion and a free-form deformation (FFD) transformation
      based on B-splines for modeling the local LV deformation. Registration is done by
      minimizing a cost function associated with the image similarity based on a global
      pixel-based matching and the smoothness of transformation. The algorithm uses a
      fast and robust optimization strategy using a multiresolution approach for the
      estimation of parameters of the deformation model. The proposed algorithm is
      evaluated for calculating the displacement curves of two expert-identified
      anatomical landmarks in apical views of the LV for 10 healthy volunteers and 14
      subjects with pathology. The proposed algorithm is also evaluated for classifying
      the regional LV wall motion abnormality using the calculation of the strain value
      at the end of systole in 288 segments as scored by two consensual experienced
      echocardiographers in a three-point scale: 1: normokinesia, 2: hypokinesia, and
      3: akinesia. Moreover, we compared the results of the proposed registration
      algorithm to those previously obtained using the other image registration
      methods. RESULTS: Regarding to the reference two experienced echocardiographers,
      the results demonstrate the proposed algorithm more accurately estimates the
      displacement curve of the two anatomical landmarks in apical views than the other
      registration methods in all data set. Moreover, the p values of the t test for
      the strain value of each segment at the end of systole measured by the proposed
      algorithm show higher differences than the other registration method. These
      differences are between each pair of scores in all segments and in three segments
      of septum independently. CONCLUSIONS: The clinical results show that the proposed
      algorithm can improve both the calculation of the displacement curve of every
      point of LV during a cardiac cycle and the classification of regional LV wall
      motion abnormality. Therefore, this diagnostic system can be used as a useful
      tool for clinical evaluation of the regional LV function.

PMID- 22847529
TI  - Protection effect of GDNF and neurturin on photosensitized crayfish neurons and
      glial cells.
AB  - Neurons and glial cells can protect each other from stress and following death by
      mutual exchange with neurotrophins. In order to examine involvement of different
      neurotrophic factors in neuroglial interactions in a photosensitized crayfish
      stretch receptor, a simple model object consisting of only two sensory neurons
      enveloped by glial cells, we studied the influence of glial cell line-derived
      neurotrophic factor (GDNF), neurturin, and ciliary neurotrophic factor (CNTF) on
      its photodynamic injury. Photodynamic treatment, which causes strong oxidative
      stress, induced firing abolition and necrosis of neurons, necrosis, and apoptosis
      of glial cells. GDNF significantly reduced photoinduced neuronal necrosis and
      neurturin but not CNTF showed a similar tendency. Both of them significantly
      reduced necrosis and apoptosis of glial cells. At the ultrastructural level,
      neurons and glial cells treated with GDNF in the darkness contained large
      mitochondria with well-developed cristae, numerous ribosomes, polysomes, rough
      endoplasmic reticulum (ER), and dictyosomes. This indicated the high level of
      bioenergetic, biosynthetic, and transport processes. Photodynamic treatment
      caused swelling and vacuolization of mitochondria, dictyosomes, and ER. It also
      impaired formation of glial protrusions and double membrane vesicles that
      transfer glial material into the neuron. GDNF prevented photoinduced mitochondria
      swelling that disturbed the cellular bioenergetics and cytoplasm vacuolization
      associated with injury of intracellular organelles. It also preserved the
      structures involved in protein synthesis and transport: rough ER, dictyosomes,
      polysomes, microtubule bundles, submembrane cisterns, and double membrane
      vesicles. GDNF-mediated maintenance of metabolism and ultrastructure of
      photosensitized neurons and glial cells may be the basis of its neuro- and glia
      protective effects.

PMID- 22847530
TI  - Tobacco nitrosamine N-nitrosonornicotine as inhibitor of neuronal nicotinic
      acetylcholine receptors.
AB  - Nitrosamines are well known for their carcinogenic potential. Recently, it was
      found that some of them may also interact with human nicotinic acetylcholine
      receptor (nAChR) subtypes. This work studied the effects of N-nitrosonornicotine
      (NNN) on recombinant rat alpha3beta4 nAChR in HEK cells as well as on nAChR
      endogenously expressed in PC12 pheochromocytoma cells and in BC3H1 muscle-type
      cells. Whole-cell recording in combination with the cell-flow technique for
      agonist and inhibitor application in the millisecond time region revealed that
      NNN inhibits the activity of neuronal nAChR expressed in HEK or PC12, whereas
      weak inhibitory effects on muscle-type nAChR were observed at NNN concentrations
      up to 3 mM. Pharmacological actions of NNN and the inhibition mechanism were
      studied in detail using recombinant alpha3beta4 nAChR expressed in HEK cells as a
      model. NNN-induced inhibition of nicotine-evoked alpha3beta4 nAChR activity was
      dose-dependent with an inhibitory constant (IC(50)) of 0.92 +/- 0.05 mM. Analysis
      based on mathematical models indicated a noncompetitive inhibition mechanism of
      the rat alpha3beta4 nAChR by NNN. NNN's mechanism of action involves acceleration
      of conversion of the receptor from active to desensitized forms. In summary, this
      work shows that NNN inhibits rat alpha3beta4 nAChR in a noncompetitive way and
      interacts weakly with muscular nAChR.

PMID- 22847535
TI  - Hormone receptor status affects locoregional control in HER2-positive breast
      cancer treated with trastuzumab.

PMID- 22847536
TI  - Low-coordinate cobalt(II) terphenyl complexes: precursors to sterically
      encumbered ketones.
AB  - Cobalt(II) diaryl complexes react with CO to afford Co(2)(CO)(8) and sterically
      encumbered ketones whose structure varies depending on the nature of the aryl
      ligands.

PMID- 22847538
TI  - Evidence for the persistence of wild Ginkgo biloba (Ginkgoaceae) populations in
      the Dalou Mountains, southwestern China.
AB  - PREMISE OF THE STUDY: The possible persistence of wild Ginkgo biloba populations
      in China has long been debated but never scientifically confirmed. We test our
      hypothesis that the extant Ginkgo populations in the Dalou Mountains (SW China)
      represent fragments of the original natural Ginkgo range and offer a range of
      pertinent perspectives on the living fossil Ginkgo's history, prehistory,
      ecology, and place in human culture-all important aspects of this highly valued
      species. METHODS: We analyzed the vegetation of the study area, determined the
      population age structure of Ginkgo, and compared it to existing fossil records.
      For supporting material, we also examined records of the lack of human presence
      before the mid-17th century in the area, the local people's beliefs regarding
      preservation of the forests and existing genetic studies. KEY RESULTS: Current
      species composition of Ginkgo forests in the Dalou Mountains agrees closely with
      floristic assemblages from fossil records bearing G. biloba. Current populations
      are found in habitats similar to those of fossil Ginkgo, which, as today, favored
      rock crevices. Female to male ratios are 3:2. Estimated ages for many of the
      trees show that Ginkgo was present in this area prior to human settlement and
      indigenous peoples of this area are unlikely to have planted Ginkgo because of
      traditional beliefs. Our results agree with existing genetic studies that show
      that these mountains were glacial refugia for G. biloba. CONCLUSIONS: The
      corroborative evidence confirms the finding that these populations represent
      fragments of the original natural Ginkgo in the valley and lower mountain slopes
      of the Dalou Mountains.

PMID- 22847537
TI  - Blockade of JNK and NFAT pathways attenuates orthopedic particle-stimulated
      osteoclastogenesis of human osteoclast precursors and murine calvarial
      osteolysis.
AB  - Particles released from orthopedic implants attract immune host defense cells to
      the bone-implant interface and contribute to development of inflammation. The
      inflammatory microenvironment supports recruitment and differentiation of
      osteoclasts, the primary culprit of osteolysis. Therefore, understanding the
      complex signals that contribute to osteoclastogenesis and osteolysis is a
      sensible approach to design strategies to inhibit bone loss. The signaling
      cascades that coordinate osteoclastogenesis have been widely investigated. These
      include MAP kinases, Akt/PI3K pathway, NF-kappaB signal transduction pathway, and
      NFAT pathway. We have recently reported that polymethylmethacrylate (PMMA)
      particles activate the NFAT pathway in murine osteoclast precursors and that NFAT
      inhibitors dose-dependently block PMMA-induced osteoclastogenesis. In the current
      study, we examined the role of JNK and NFATc1 in mice in response to PMMA
      particles using murine calvaria model. We show that locally administered MAPK/JNK
      inhibitor SP600125 and calcineurin/NFAT inhibitor cyclosporine-A effectively
      blocked PMMA-induced osteolysis in murine calvaria. To buttress the clinical
      relevance of JNK/NFATc1-based regulation of PMMA-induced osteoclastogenesis, we
      evaluated the effect of PMMA using human macrophages. We demonstrate that
      SP600125 and cyclosporine-A abolished particle-induced osteoclastogenesis in
      human osteoclast progenitors retrieved from patients undergoing total hip
      replacement. Thus JNK and NFATc1 appear to act as significant mediators of
      orthopedic particle-induced osteolysis in humans.

PMID- 22847539
TI  - Anonymous and EST-based microsatellite DNA markers that transfer broadly across
      the fig tree genus (Ficus, Moraceae).
AB  - PREMISE OF THE STUDY: We developed a set of microsatellite markers for broad
      utility across the species-rich pantropical tree genus Ficus (fig trees). The
      markers were developed to study population structure, hybridization, and gene
      flow in neotropical species. METHODS AND RESULTS: We developed seven novel primer
      sets from expressed sequence tag (EST) libraries of F. citrifolia and F. popenoei
      (subgen. Urostigma sect. Americana) and optimized five previously developed
      anonymous loci for cross-species amplification. The markers were successfully
      tested on four species from the basal subgenus Pharmacosycea sect. Pharmacosycea
      (F. insipida, F. maxima, F. tonduzii, and F. yoponensis) and seven species of the
      derived subgenus Urostigma (F. citrifolia, F. colubrinae, F. costaricana, F.
      nymphaeifolia, F. obtusifolia, F. pertusa, and F. popenoei). The 12 markers
      amplified consistently and displayed polymorphism in all the species.
      CONCLUSIONS: This set of microsatellite markers is transferable across the
      phylogenetic breadth of Ficus, and should therefore be useful for studies of
      population structure and gene flow in approximately 750 fig species worldwide.

PMID- 22847540
TI  - Ontologies as integrative tools for plant science.
AB  - PREMISE OF THE STUDY: Bio-ontologies are essential tools for accessing and
      analyzing the rapidly growing pool of plant genomic and phenomic data. Ontologies
      provide structured vocabularies to support consistent aggregation of data and a
      semantic framework for automated analyses and reasoning. They are a key component
      of the semantic web. METHODS: This paper provides background on what bio
      ontologies are, why they are relevant to botany, and the principles of ontology
      development. It includes an overview of ontologies and related resources that are
      relevant to plant science, with a detailed description of the Plant Ontology
      (PO). We discuss the challenges of building an ontology that covers all green
      plants (Viridiplantae). KEY RESULTS: Ontologies can advance plant science in four
      keys areas: (1) comparative genetics, genomics, phenomics, and development; (2)
      taxonomy and systematics; (3) semantic applications; and (4) education.
      CONCLUSIONS: Bio-ontologies offer a flexible framework for comparative plant
      biology, based on common botanical understanding. As genomic and phenomic data
      become available for more species, we anticipate that the annotation of data with
      ontology terms will become less centralized, while at the same time, the need for
      cross-species queries will become more common, causing more researchers in plant
      science to turn to ontologies.

PMID- 22847542
TI  - Leaf size in three generations of a dioecious tropical tree, Ocotea tenera
      (Lauraceae): Sexual dimorphism and changes with age.
AB  - PREMISE OF THE STUDY: In dioecious species, selection should favor different leaf
      sizes in males and females whenever the sexes experience distinct environments or
      constraints such as different costs of reproduction. We took advantage of a long
      term experimental study of Ocotea tenera (Lauraceae), a dioecious understory tree
      in Monteverde, Costa Rica, to explore leaf size differences between genders and
      age classes across generations. METHODS: We measured leaf size in adult trees in
      a natural population, in their adult F(1) offspring in two experimental
      populations, and in their F(2) offspring at the seedling stage. Individual trees
      were measured at various times over 20 yr. RESULTS: Leaves of female trees
      averaged 8% longer and 12% greater in area than those of males. Leaves were
      sexually dimorphic at reproductive maturity. Leaf size declined during the
      lifetime of most trees. Heritability estimates for leaf length were positive
      although not statistically significant (h(2) = 0.63, SE = 0.48, P = 0.095).
      CONCLUSIONS: We ruled out the ecological causation hypothesis for sexual
      dimorphism in leaf size because male and female trees co-occurred in the same
      habitats. Sexual dimorphism appeared not to result from genetic or phenotypic
      correlations with other traits such as height or flower size. Rather, females
      appear to compensate for higher costs of reproduction and diminished
      photosynthetic capacity by producing larger leaves. Additive genetic variance in
      leaf size, a prerequisite for an evolutionary response to selection for sexual
      dimorphism, was suggested by positive (although only marginally significant)
      heritability estimates.

PMID- 22847541
TI  - Characterization of new microsatellite loci isolated from Santiria trimera
      (Burseraceae).
AB  - PREMISE OF THE STUDY: To study the genetic structure among three morphotypes of
      an African rainforest tree species, Santiria trimera, nuclear microsatellite
      markers were isolated and characterized. METHODS AND RESULTS: Seven polymorphic
      loci were isolated using a pyrosequencing-based protocol and successfully
      amplified on three different morphotypes of S. trimera. For six of the seven
      loci, there is at least one private allele for one of the three morphotypes. The
      mean effective number of alleles is about four for each of the three morphotypes.
      CONCLUSIONS: These microsatellite markers are promising to explore the genetic
      delimitation among sympatric morphotypes found in Gabonese forests and to study
      the spatial genetic structure within each gene pool.

PMID- 22847543
TI  - Multiple origins of congested inflorescences in Cyperus s.s. (Cyperaceae):
      developmental and structural evidence.
AB  - PREMISE OF THE STUDY: The understanding of homoplasic structures becomes more
      relevant when they are complex and define large angiosperm taxa. Inflorescence
      architecture usually fulfills both features, as happens with Cyperus, a genus
      with two taxonomical subdivisions characterized either by alternative expressions
      of Kranz anatomy (C(3) or C(4)) or inflorescence shape (condensed or lax). Those
      subdivisions are not completely congruent because at least one of these presumed
      characters has evolved several times. We focused a SEM study on the inflorescence
      development in species with condensed inflorescences and different photosynthetic
      anatomy to test the possibility that condensed inflorescences of subgen.
      Anosporum (C(3) anatomy) have evolved independently from those of subgen. Cyperus
      (C(4) anatomy). METHODS: Freshly collected inflorescences of C. entrerianus, C.
      eragrostis, C. oxylepis, and C. incomtus were studied using stereoscopic and
      scanning electron microscopy. KEY RESULTS: Condensed inflorescences of Cyperus
      species with C(3) and C(4) anatomy had differences in structure and development:
      (1) mature structure, (2) position of second-order branching initiation in the
      first developmental stage of the inflorescence, (3) main axis development and
      elongation, and branching development, (4) types of ramifications, (5)
      phyllotaxis and symmetry. CONCLUSIONS: Results support multiple origins of
      condensed inflorescences in Cyperus, based especially on differences in timing
      during development and elongation of the main axis and branches, branching
      pattern and phyllotaxis. Structure and development may be the key to using
      inflorescence morphology as an external feature to distinguish large natural
      groups within Cyperus based on vegetative anatomy.

PMID- 22847544
TI  - Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be
      complicated with chronic active hepatitis and hypothyroidism.
AB  - PURPOSE: To describe a case of autosomal-dominant (AD)-chronic mucocutaneous
      candidiasis (CMC) with a signal transducer and activator of transcription (STAT)
      1 gene mutation, and some of the important complications of this disease such as
      chronic hepatitis. METHODS: We present a 23-year-old woman with CMC, chronic
      active hepatitis, and hypothyroidism. Her father also had CMC. We performed
      several immunological analyses of blood and liver samples, and searched for gene
      mutations for CMC in the patient and her father. RESULTS: We identified the
      heterozygous substitution c.821 G > A (p.Arg274Gln) in the STAT1 gene of both the
      patient and her father. The level of beta-glucan induced interferon (IFN)-gamma
      in her blood cells was significantly low. Immunoblot analysis detected serum anti
      interleukin (IL)-17 F autoantibody. She was found to have increased (low-titer)
      antibodies related to her hypothyroidism and hepatitis. Her serum IL-18 levels
      fluctuated with her AST and ALT levels. Liver biopsy revealed CD68-positive cell
      infiltration and IL-18 expression in the sinusoidal regions. These results
      suggest that the chronic active hepatitis in this patient may be exacerbated by
      the excessive IL-18 accumulation caused by recurrent mucocutaneous fungal
      infection, and decreased IFN-gamma production. CONCLUSIONS: AD-CMC is known to be
      caused by a gain-of-function mutation of the STAT1 gene. Chronic active hepatitis
      is a rare complication of AD-CMC, with currently unknown pathogenesis. It seems
      that the clinical phenotype in this patient is modified by autoimmune mechanisms
      and cytokine dysregulation. AD-CMC can be complicated by various immune disorders
      including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

PMID- 22847545
TI  - Increased serum circulatory levels of interleukin 17F in type 1 reactions of
      leprosy.
AB  - PURPOSE: Leprosy is a chronic infectious disease caused by Mycobacterium leprae
      affecting mainly skin and peripheral nerves. Acute inflammatory episodes in the
      borderline immunological spectrum of the disease cause severe nerve and tissue
      damage leading to deformities. Finding of any serological marker for leprosy
      reactions will help in prediction of reactions and in early treatment
      intervention. The objective of this study was to measure the serum circulatory
      levels of Interleukin 17F (IL 17F) and to correlate the levels with type 1 and
      type 2 reactional states and with clinico-histopathological spectrum of leprosy.
      We studied IL 17F to delineate its role and its clinical implications in leprosy
      reactions. METHODS: Patients were classified based on the Ridley DS and Jopling
      WH Classification and blood samples (5 ml each) were collected from 80 active
      untreated leprosy cases in Type 1 reaction (T1R), 21 cases in Type 2 (Erythema
      Nodosum Leprosum ENL) reaction (T2R), 80 cases without reaction (NR), and 94 non
      leprosy cases (NL). Serum was separated and measured for IL 17F levels using
      ELISA (Commercial Kits, R&D Systems Inc., USA). RESULTS: IL 17F levels were
      significantly higher in the T1R group when compared to the NR group (p < 0.001).
      The borderline lepromatous group showed the highest levels of IL 17F among the
      other groups in the disease spectrum. Bacteriological index (BI) showed negative
      correlation with the IL 17F levels. CONCLUSION: The results specify that serum
      circulatory levels of IL 17F are elevated during T1Rs in the borderline spectrum
      of the disease and thus may play a role in the regulation of inflammatory
      responses associated with reactions in leprosy.

PMID- 22847547
TI  - Sexual medicine: Rapid-onset avanafil effective for ED.

PMID- 22847546
TI  - Primary immunodeficiency diseases worldwide: more common than generally thought.
AB  - PURPOSE: Primary immunodeficiency diseases (PIDs) comprise at least 176
      hereditary disorders that are thought to be individually and collectively rare.
      The actual prevalence and incidence of PIDs remains unclear, but recent
      epidemiologic studies have suggested that PIDs are more common than generally
      thought. Based on these studies, we attempted to estimate the worldwide
      prevalence and incidence of PIDs. METHODS: Using data from registries and two
      recent epidemiologic surveys estimating the frequencies of PIDs, we extrapolated
      the frequencies reported for certain countries to the populations of continents
      and of the world. RESULTS: Our upper estimates suggest that six million people
      may be living with a PID worldwide, whereas only 27,000-60,000 have been
      identified to date (all national registries and the Jeffrey Modell Centers
      Network, respectively). For Europe, our upper estimate was 638,000 cases, and
      15,052 cases are currently registered (2.27 %). In Africa, up to 902,631 people
      may have a PID, whereas only 1,016 cases are currently registered. We also found
      that PIDs were prevalent not only in children, but also in adults, who were
      strongly underrepresented in registries. CONCLUSION: Specific, dedicated
      epidemiologic studies are required, to obtain more realistic statistics for PIDs
      and to increase the awareness of physicians and public health systems about these
      diseases. Furthermore, the field of PIDs is continually growing, and this is
      likely to lead to a revision of the definition of these conditions, potentially
      increasing estimates of their impact on both adults and children, at the
      population level.

PMID- 22847548
TI  - Sexual medicine: the psychological effects of recreational PDE5 inhibitor use.

PMID- 22847549
TI  - Current status of robot-assisted radical cystectomy for bladder cancer.
AB  - Radical cystectomy is associated with significant morbidity. However, the
      introduction of minimally invasive surgical approaches has attempted to improve
      perioperative outcomes and decrease surgical complications. Emerging data suggest
      that robot-assisted radical cystectomy (RARC) might have some advantages compared
      with open radical cystectomy (ORC). However, the oncologic performance of RARC in
      patients with locally advanced disease is currently unclear, making it crucial to
      select patients for the procedure very carefully. No long-term prospective
      studies comparing the robot-assisted and open techniques have been reported.
      Until long-term oncologic outcomes of RARC and the results of currently ongoing
      randomized trials comparing the two techniques become available, ORC remains the
      gold standard.

PMID- 22847550
TI  - BDNF-dependent accumulation of palmitoleic acid in CNS neurons.
AB  - Although it is known that brain-derived neurotrophic factor (BDNF) plays a
      critical role in neuronal survival and differentiation, its effect on lipid
      homeostasis is poorly understood. To understand them, we here investigated the
      effect of BDNF on the fatty acid composition of primary neurons. A detailed
      analysis of the fatty acid composition of BDNF-stimulated primary neurons
      revealed that BDNF treatment led to a significant and selective increase in
      intracellular palmitoleic acid (PLO) levels. Correspondingly, BDNF induced the
      expression of the enzyme responsible for PLO synthesis [stearoyl-CoA desaturase
      1]. In addition, this increase was suppressed by K252a, an inhibitor for
      tropomyosin-related kinase (Trk) receptors, indicating that BDNF-dependent
      increase in the PLO was mediated through the activation of TrkB. Further, PLO in
      culture media was reduced by BDNF treatment. This result suggested that BDNF
      suppressed extracellular release of PLO. Taken together, these data indicate that
      BDNF increases intracellular PLO both by activating its biosynthesis and by
      suppressing its extracellular release.

PMID- 22847552
TI  - Perspectives on ab initio molecular simulation of excited-state properties of
      organic dye molecules in dye-sensitised solar cells.
AB  - In this mini-review, we summarise and critique the emerging field of quantum
      based molecular simulation of dye-sensitised solar cells (DSSCs), with particular
      focus on the deployment of organic-based dyes therein. We assess the underlying
      methodologies, including developments, pitfalls and challenges, whilst gauging
      predictive performance vis-a-vis experimental performance. The predictive
      capabilities of simulation methods with respect to elucidation of underlying
      methods is considered in the light of progress towards the ultimate goal of
      predictive in silico design of DSSCs, to complement hand-in-hand experimental
      approaches in the development of state-of-the-art DSSC devices.

PMID- 22847551
TI  - Chronic inflammation alters production and release of glutathione and related
      thiols in human U373 astroglial cells.
AB  - Neurons rely on glutathione (GSH) and its degradation product cysteinylglycine
      released by astrocytes to maintain their antioxidant defences. This is
      particularly important under conditions of inflammation and oxidative stress, as
      observed in many neurodegenerative diseases including Alzheimer's disease (AD).
      The effects of inflammatory activation on intracellular GSH content and the
      extracellular thiol profile (including cysteinylglycine and homocysteine) of
      astrocytes were investigated. U373 astroglial cells exposed to IL-1beta and TNF
      alpha for up to 96 h showed a dose-dependent increase in IL-6 release, indicative
      of increasing pro-inflammatory cellular activation. With increasing
      concentrations of IL-1beta and TNF-alpha (0.01-1 ng/ml), an increase in both
      intracellular and extracellular GSH levels was observed, followed by a return to
      control levels in response to higher concentrations of IL-1beta and TNF-alpha.
      Extracellular levels of cysteinylglycine decreased in response to all
      concentrations of IL-1beta and TNF-alpha. In contrast, levels of the neurotoxic
      thiol homocysteine increased in a dose-dependent manner to IL-1beta and TNF-alpha
      induced activation. Our results suggest that chronically activated astrocytes in
      the brain might fail to adequately maintain GSH substrate delivery to neurons,
      thus promoting neuronal vulnerability. They might also explain the elevated
      levels of homocysteine found in the brains and serum of patients with AD.

PMID- 22847553
TI  - A successful treatment of arterial ischemic stroke with stent insertion in a
      child with congenital heart disease.
AB  - INTRODUCTION: Diagnosis of arterial ischemic stroke in pediatric patients is
      often delayed due to the uncertainty and variability of clinical symptoms. Early
      diagnosis of arterial ischemic stroke can bring a favorable prognosis with prompt
      thrombolytic therapy or stent insertion, via transfemoral cerebral arteriogram.
      Acute thrombolytic therapy is rarely attempted in children because of the delayed
      diagnosis. PATIENT AND METHOD: We report a case of a 4-year-old girl with complex
      heart disease who was presented with arterial ischemic stroke at the right distal
      internal carotid artery and successfully treated by stent insertion in which
      repeated thrombolysis or ballooning had failed. RESULT: Left hemiparesis was
      nearly recovered 6 days after the stent insertion. The mean flow velocity of the
      right middle cerebral artery has slightly improved compared to that of the
      initial study. She has been followed-up for 6 months in the outpatient clinic
      without neurologic sequelae. CONCLUSION: This case suggests that intracranial
      stent insertion may be a safe and an effective modality in young children, when
      the thrombolytic therapy or ballooning is inapplicable. Additionally,
      transcranial Doppler ultrasonography is useful to monitor the cerebral blood flow
      after stent insertion in children.

PMID- 22847555
TI  - Clinical characteristics of Japanese patients with eosinophilic esophagitis and
      eosinophilic gastroenteritis.
AB  - BACKGROUND: The clinical characteristics of Japanese patients with eosinophilic
      esophagitis (EoE) and eosinophilic gastroenteritis (EGE) have not been fully
      clarified. For understanding the pathogenesis as well as providing support for
      accurate diagnosis, precise information regarding clinical characteristics of
      these diseases is important. METHODS: A questionnaire-based survey of EoE and EGE
      was conducted in 1,078 teaching hospitals. Clinical data of patients with
      confirmed EoE or EGE diagnosed from 2004 to 2009 were collected. RESULT: Clinical
      data from 26 patients with EoE and 144 patients with EGE were collected. The mean
      ages of patients in both groups were in the 40s. Those with EoE frequently
      complained of dysphagia and heartburn, and had characteristic endoscopic features
      such as longitudinal furrows and multiple concentric rings in the esophagus,
      while only 34% had peripheral eosinophilia. Patients with EGE frequently
      complained of abdominal pain and diarrhea, and approximately 80% of them have
      peripheral eosinophilia. They did not have characteristic endoscopic features
      helpful for diagnosis. Computed tomography (CT) findings and the presence of
      peripheral eosinophilia were diagnostic for EGE. EGE patients with a small
      intestinal involvement showed the highest peripheral eosinophil counts.
      Glucocorticoid administration was the most widely used treatment for these
      diseases and its effect was favorable for at least induction of remission.
      CONCLUSION: EGE is more prevalent than EoE in Japan. Patients with EGE have
      abdominal pain and diarrhea, high peripheral eosinophil counts, and
      gastrointestinal wall thickening identifiable by CT findings, while EoE is
      characterized by dysphagia and characteristic endoscopic features.

PMID- 22847554
TI  - Perihilar cholangiocarcinoma: a surgeon's viewpoint on current topics.
AB  - Perihilar cholangiocarcinomas are defined anatomically as "tumors that are
      located in the extrahepatic biliary tree proximal to the origin of the cystic
      duct". However, as the boundary between the extrahepatic and intrahepatic bile
      ducts is not well defined, perihilar cholangiocarcinomas potentially include two
      types of tumors: one is the "extrahepatic" type, which arises from the large
      hilar bile duct, and the other is the "intrahepatic" type, which has an
      intrahepatic component with the invasion of the hepatic hilus. The new TNM
      staging system published by the International Union Against Cancer (UICC) has
      been well revised with regard to perihilar cholangiocarcinoma, but it still lacks
      stratification of patient prognosis and has little applicability for assessing
      the feasibility of surgical treatment; therefore, further refinement is
      essential. Most patients with perihilar cholangiocarcinomas present with
      jaundice, and preoperative biliary drainage is mandatory. Previously,
      percutaneous transhepatic biliary drainage was used in many centers; however, it
      is accepted that endoscopic naso-biliary drainage is the most suitable method of
      preoperative drainage. Portal vein embolization is now widely used as a
      presurgical treatment for patients undergoing an extended hepatectomy to minimize
      postoperative liver dysfunction. The surgical resection of a perihilar
      cholangiocarcinoma is technically demanding and continues to be the most
      difficult challenge for hepatobiliary surgeons. Because of advances in diagnostic
      and surgical techniques, surgical outcomes and survival rates after resection
      have steadily improved. However, survival, especially for patients with lymph
      node metastasis, is still unsatisfactory, and the establishment of adjuvant
      chemotherapy is necessary. Further synergy of endoscopists, radiologists,
      oncologists, and surgeons is required to conquer this intractable disease.

PMID- 22847556
TI  - Stereotaxic surgery for excitotoxic lesion of specific brain areas in the adult
      rat.
AB  - Many behavioral functions in mammals, including rodents and humans, are mediated
      principally by discrete brain regions. A common method for discerning the
      function of various brain regions for behavior or other experimental outcomes is
      to implement a localized ablation of function. In humans, patient populations
      with localized brain lesions are often studied for deficits, in hopes of
      revealing the underlying function of the damaged area. In rodents, one can
      experimentally induce lesions of specific brain regions. Lesion can be
      accomplished in several ways. Electrolytic lesions can cause localized damage but
      will damage a variety of cell types as well as traversing fibers from other brain
      regions that happen to be near the lesion site. Inducible genetic techniques
      using cell-type specific promoters may also enable site-specific targeting. These
      techniques are complex and not always practical depending on the target brain
      area. Excitotoxic lesion using stereotaxic surgery, by contrast, is one of the
      most reliable and practical methods of lesioning excitatory neurons without
      damaging local glial cells or traversing fibers. Here, we present a protocol for
      stereotaxic infusion of the excitotoxin, N-methyl-D-aspartate (NMDA), into the
      basolateral amygdala complex. Using anatomical indications, we apply stereotaxic
      coordinates to determine the location of our target brain region and lower an
      injection needle in place just above the target. We then infuse our excitotoxin
      into the brain, resulting in excitotoxic death of nearby neurons. While our
      experimental subject of choice is a rat, the same methods can be applied to other
      mammals, with the appropriate adjustments in equipment and coordinates. This
      method can be used on a variety of brain regions, including the basolateral
      amygdala, other amygdala nuclei, hippocampus, entorhinal cortex and prefrontal
      cortex. It can also be used to infuse biological compounds such as viral vectors.
      The basic stereotaxic technique could also be adapted for implantation of more
      permanent osmotic pumps, allowing more prolonged exposure to a compound of
      interest.

PMID- 22847557
TI  - [Nutritional therapy in traumatic brain injury :  Update 2012].
AB  - Severe traumatic brain injury ranks among the most common causes of death in
      young adults in western countries. Severe traumatic brain injury is typically
      followed by a pronounced pathophysiological cascade that accounts for many
      deaths. The aim of intensive care medicine after traumatic brain injury is to
      minimize and to control the consequences of this potentially fatal cascade. The
      avoidance of hypoxemia, arterial hypotension, intracranial hypertension,
      hyperthermia, hyperglycemia, hypoglycemia and thromboembolic complications is
      essential in preventing this cascade. The effect of nutrition has been rather
      underestimated as a means of improving the outcome after traumatic brain injury.
      Nutrition should be started within the first 24 h after trauma. Enteral, wherever
      applicable, should be the route of administration of nutrition. Enteral
      administration of the whole calculated calorie requirement on day 1 after trauma,
      if possible, lowers the infection and overall complication rates. The present
      review gives an update of a practical approach to nutrition in traumatic brain
      injury.

PMID- 22847558
TI  - [Coagulation management of trauma patients with unstabile circulation :
      establishment of a hemoglobin-oriented standard operating procedure].
AB  - INTRODUCTION: Massive hemorrhage is the leading cause of death in the first few
      hours following multiple trauma, therefore, early and aggressive treatment of
      clotting disorders and surgical intervention to stop the bleeding are of utmost
      importance. However, commonly performed clotting tests have a considerable
      latency of at least 30-45 min, whereas hemoglobin (Hb) levels can be tested very
      quickly. If a multiple trauma patient has already received fluid resuscitation, a
      certain relationship may be observed between the hemoglobin value and the
      development of clotting disturbances. Hence, hemoglobin may be a useful and
      rapidly available parameter for guiding the initial treatment of clotting
      disturbances in multiple trauma patients. METHODS: A Hb-guided algorithm has been
      developed to initiate initial clotting therapy. The algorithm contains three
      stages of different aggressive clotting therapy with fibrinogen, prothrombin
      complex concentrate (PCC), factor VIIa, tranexamic acid and desmopressin,
      depending on the first Hb value measured. For admission Hb levels > 5.5 mmol/l
      (~8.8 g/dl) coagulation therapy is managed on the basis of the laboratory tests
      and if in doubt 2 g fibrinogen is administered. For admission Hb levels between
      5.5 mmol/l (~8.8 g/dl) and 4 mmol/l (~6.5 g/dl) 2-4 g fibrinogen and 2,500-3,000
      IU PCC are administered and tranexamic acid and desmopressin administration
      should be considered. For admission Hb levels < 4 mmol/l (~6.5 g/dl) 4-6 g
      fibrinogen, 3,000-5,000 IU PCC and 1 mg factor VIIa should be administered and
      tranexamic acid and desmopression should be considered. All drugs mentioned
      should be stored in a special "coagulation box" in the hospital pharmacy and this
      box is brought immediately to the patient on demand. In addition to the use of
      clotting factors, infusions should be performed with balanced crystalloids and
      transfusions with an RBC/FFP ratio of 2:1-1:1. To assess the efficiency of the
      algorithm the routinely measured clotting parameters at trauma bay admission were
      compared with intensive care unit (ICU) admission and the standardized mortality
      ratio (SMR) was calculated. RESULTS: During a 6-month investigation period 71
      severe multiple trauma patients were admitted to the trauma center and 19
      patients were treated using the coagulation box of which 13 required massive
      transfusions. The routinely used clotting parameters markedly improved between
      admission to the trauma bay and ICU admission: Quick 61% versus 97% (p < 0.001),
      partial prothromboplastin time (PTT) 50 s versus 42 s (not significant),
      fibrinogen 1.7 g/l versus 2.15 g/l (not significant). Of the 19 patients 11 (58%)
      survived. The revised injury severity classification (RISC) predicted a survival
      rate of 40%, which corresponds to an SMR of 0.69, thus implying a higher survival
      rate than predicted. CONCLUSIONS: The Hb-driven algorithm, in combination with
      the coagulation box and the early use of clotting factors, may be a simple and
      effective tool for improving coagulopathy in multiple trauma patients.

PMID- 22847560
TI  - A novel tricyclic polyketide and its biosynthetic precursor azaphilone
      derivatives from the endophytic fungus Dothideomycete sp.
AB  - Azaphilone derivatives 1 and 2 and a novel tricyclic polyketide 3, together with
      a known azaphilone, austdiol (4), were isolated from the endophytic fungus
      Dothideomycete sp., which was isolated from a Thai medicinal plant, Tiliacora
      triandra. Compound 3 is the first polyketide having a tricyclic 6,6,6 ring
      system, which is similar to that of a terpenoid skeleton. The absolute
      configurations of stereogenic centers in 1-3 were addressed by Mosher's method
      and biosynthetic analogy with a known azaphilone isolated from the same fungus.
      Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.

PMID- 22847559
TI  - [Removal of epidural catheter under dual antiplatelet therapy following acute
      coronary syndrome : scenario without special consideration to the current
      guidelines on epidural regional anesthesia].
AB  - This article reports the case of a patient who developed acute coronary syndrome
      while receiving postoperative pain treatment via an epidural catheter (EC).
      Platelet function testing was performed before removal of the EC to assess the
      bleeding risk under ongoing dual antiplatelet therapy. Platelet function testing
      showed low responsiveness to clopidogrel and acetylsalicylic acid (ASS). The EC
      was removed uneventfully and clopidogrel was subsequently replaced by prasugrel
      and platelet function showed improved depression of thrombocyte aggregation.
      Possible reasons for low responsiveness to clopidogrel and ASS, such as drug-drug
      interactions with proton pump inhibitors and genetic factors are discussed.

PMID- 22847561
TI  - An uncommon shape of epiglottis misleading as acute epiglottitis.
AB  - We report a case of a 31-year-old Japanese woman with an uncommon shape of
      epiglottis misleading as acute epiglottitis. She presented with high fever,
      arthralgia, general fatigue and strong throat pain. Laryngeal fiberscopy showed a
      markedly swollen epiglottis suggestive of acute epiglottitis, though she had no
      signs of asphyxia. A careful observation and detailed medical history ruled out
      acute epiglottitis. However, without clinical discretion, it might have been
      misinterpreted as acute epiglottitis. She was diagnosed later with Behcet's
      disease, which is reported to present pharyngeal stenosis. Two years later, a
      repeat laryngeal fiberscopy showed exactly the same appearance of the epiglottis,
      suggesting its shape to be permanent. The cause of this misleading shape of the
      epiglottis in this patient is yet unknown. For similar cases, a possibility of
      this kind of epiglottis should be considered before diagnosing as acute
      epiglottitis.

PMID- 22847562
TI  - Sarcoid-like reaction in Cryptococcus neoformans infection.
AB  - We report a patient with Cryptococcus (C.) neoformans infection, who developed a
      case of sarcoid-like reaction (SLR). There have been reports of SLRs associated
      with malignancies. Although differentiating sarcoidosis from SLR is difficult,
      the patient was diagnosed as SLR because propionibacterium acnes bacterial (PAB)
      antibody staining of biopsy specimens was negative and the chest radiological
      findings improved after antifungal treatment. To our knowledge, this is the first
      report of SLR occurring during cryptococcal infection, and we believe that
      cryptococcal infection should be considered as a potential cause of SLR.

PMID- 22847563
TI  - Stage IV malignant melanoma of unknown primary site in a young man.
AB  - Metastatic melanoma of unknown primary is a rare entity with low life expectancy.
      Inoperable metastatic malignant melanoma in lungs has a survival rate of <6%.
      Regression of the primary lesion is a well-documented theory in the literature,
      since melanoma is one of the tumours that can undergo regression. We present a
      case of a young man with metastatic malignant melanoma in lungs, whose survival
      duration is longer than expected even without metastasectomy.

PMID- 22847564
TI  - Size does matter.

PMID- 22847565
TI  - The importance of challenging your diagnosis even in straightforward cases.
AB  - The art of diagnosis consists in the recognition of signs and symptoms and their
      interpretation under the light of individual circumstances obtained from the
      patient's history. In medicine we encounter cases that are straightforward and
      cases that are complex as they are the result of a rare disease or of uncommon
      presentation of a common disorder. We present in this paper the case of a patient
      with a non-healing traumatic wound to her shin, which after unsuccessful
      treatments was biopsied and an unexpected diagnosis of necrobiosis lipoidica
      diabeticorum was made. This led to the institution of disease-targeted wound care
      leading to complete resolution in a short period of time.

PMID- 22847567
TI  - The rare complication of Behcet's syndrome: concomitance of coronary slow flow
      with acute coronary syndrome.

PMID- 22847566
TI  - Enteral vancomycin and probiotic use for methicillin-resistant Staphylococcus
      aureus antibiotic-associated diarrhoea.
AB  - A geriatric patient status post intraabdominal surgery presented with persistent
      diarrhoea and heavy intestinal methicillin-resistant Staphylococcus aureus (MRSA)
      growth after multiple courses of antibiotic therapy. Additionally, swab cultures
      of the anterior nares tested positive for MRSA. In order to impede infection and
      prevent future complications, the patient received a 10-day course of vancomycin
      oral solution 250 mg every 6 h, 15-day course of Saccharomyces boulardii 250 mg
      orally twice daily and a 5-day course of topical mupirocin 2% twice daily
      intranasally. Diarrhoea ceased during therapy and repeat cultures 11 days after
      initiating therapy demonstrated negative MRSA growth from the stool and nares.
      Further repeat cultures 5 months later revealed negative MRSA growth in the
      stools and minimal MRSA growth in the nares. Overall, enteral vancomycin and
      probiotics successfully eradicated MRSA infection without intestinal recurrence.
      Although the results were beneficial treating MRSA diarrhoea for our patient,
      these agents remain highly controversial.

PMID- 22847568
TI  - Posterior talar fracture with dislocation of both talo-navicular and subtalar
      joints: a variant type II of the Sneppens classification.
AB  - A 63-year-old man fell from a ladder, thus causing an axial compression injury to
      the right ankle. Severe deformity was evident and the ankle could not be reduced
      by simple manipulation. The skin was tented and appearing critically contused.
      Radiographs revealed an oblique fracture of the posterior aspect of the talar
      body with dislocation of both the talo-navicular and subtalar joints, an injury
      previously not described in the literature. The fracture-dislocation was
      anatomically reduced within 3 h of presentation and stability achieved with two
      headless buried compression screws. CT scan confirmed anatomical reduction and
      the patient remained non-weight bearing in a cast for 6 weeks. One year
      postoperatively, the patient remains pain-free with no radiological signs of
      avascular necrosis of the talus. This injury is unique and despite its severity
      and soft tissue compromise good quality reduction and internal fixation resulted
      in an excellent clinical outcome.

PMID- 22847569
TI  - Early recanalisation of cerebral venous sinus thrombosis in an unusual case
      associated with severe protein S deficiency.
AB  - An inherited or acquired deficiency of protein S leads to a prothrombotic state,
      with predisposition to venous thrombosis. We describe a case of cerebral venous
      sinus thrombosis (CVST) associated with acquired protein S deficiency and
      recanalisation within 15 days of anticoagulation. A 38-year-old man presented
      with recurrent headache, vomiting, altered sensorium and one episode of transient
      left hemiparesis. Magnetic resonance venography showed poor flow in the deep
      cerebral venous sinuses with extensive collateral venous channel formation, which
      resolved after 15 days of anticoagulation, along with clinical improvement. Serum
      protein S activity was found to be markedly low (16% of biological reference).
      CVST should be suspected in a patient with acute features of raised intracranial
      pressure or focal neurological deficit, and a patient without obvious clinical
      predisposition for a prothrombotic state should be evaluated for underlying
      thrombophilic states like protein S deficiency.

PMID- 22847570
TI  - Contrary to expectation--a case of left-sided acute appendicitis.

PMID- 22847571
TI  - The 'cut and push' technique: is it really safe?
AB  - Percutaneous endoscopic gastrostomy (PEG) feeding is routinely used as an
      endoscopic and effective method for providing enteral nutrition in those whose
      oral access has been diminished or lost. One technique for removal of the PEG is
      cutting the tube at the skin level and allowing the tube and internal flange to
      pass spontaneously. This is known as the 'cut and push' method. Several studies
      have concluded that the 'cut and push' method is a safe and cost-effective
      method. This case demonstrates a rare cause of small bowel obstruction following
      the 'cut and push' method for PEG replacement, with only a few other cases been
      reported. This method of removal should be avoided in patients with previous
      abdominal surgery. It is important that the PEG flange is retrieved
      endoscopically or an alternative PEG tube (designed to be completely removed
      through the skin) is used to prevent this complication occurring in such
      individuals.

PMID- 22847572
TI  - Relationship between dye-iodine binding and cell voltage in dye-sensitized solar
      cells: a quantum-mechanical look.
AB  - It has been proposed that iodine binding to dyes may actually decrease the cell
      efficiency of a dye-sensitized solar cell. A previous experimental study showed
      that a two-atom change from oxygen to sulfur increased recombination of iodine
      with injected electrons by a factor of approximately 2. Here, it is shown that
      iodine binding is a plausible explanation for this effect. The steric and
      conjugation effects are quantified separately using a set of model compounds.
      Quantum-chemical calculations show that elongation of the hydrocarbon chain has
      only an insignificant effect on the iodine and bromine binding to the chalcogen
      atoms (O, S, Se). The conjugation, however, significantly disfavors the iodine
      and bromine interaction. Iodine and bromine binding to the dye and model
      compounds containing sulfur is significantly more favorable than to their oxygen
      containing counterparts. Bromine binding to dyes is shown to be stronger than
      that of iodine. Accordingly, bromine binding to dyes may contribute significantly
      to the observed lower efficiencies in cells using Br(3)(-)/Br(-) as the redox
      couple.

PMID- 22847573
TI  - Short-term outcomes in obese patients after colectomy for adenocarcinoma at a
      bariatric center.
AB  - INTRODUCTION: Obesity (body mass index >=30) is associated with worse outcomes
      after colon cancer surgery. Most research, however, has been performed outside
      bariatric centers of excellence. We sought to determine the relationship between
      obesity and outcomes after colon cancer resection when performed at a center with
      bariatric expertise. METHODS: We performed a retrospective review of 245
      consecutive patients undergoing elective colectomy for adenocarcinoma at a single
      institution from 2008 to 2009. Body mass index, major and minor postoperative
      complications, tumor characteristics, lymph node yield, type of resection, and
      operating times were determined. RESULTS: Complication rates, operative times,
      and lymph node counts were all similar between the two weight groups. Obese
      patients had similar tumor characteristics at all stages when compared with
      nonobese patients. On multivariate analysis, obesity did not correlate with tumor
      size, tumor differentiation, or presence of lymphovascular or perineural
      invasion. CONCLUSION: We conclude that obese patients undergoing colon cancer
      resection at a bariatric center of excellence have similar tumor characteristics
      and equivalent short-term outcomes as do nonobese patients.

PMID- 22847574
TI  - Surgical management trends for cholangiocarcinoma in the USA 1998-2009.
AB  - BACKGROUND: Surgical advancements have improved outcomes for cholangiocarcinoma
      (CCA) patients, but this expertise is not uniformly available. This research
      examines CCA surgical treatment patterns. METHODS: A retrospective analysis of
      the U.S. Nationwide Inpatient Sample from 1998-2009 identified CCA patients at
      high-volume (HV) versus low-volume (LV) hospitals, and teaching versus
      nonteaching hospitals. We performed multinomial and multivariate logistic
      regressions to compare differences of surgical treatment between HV vs. LV
      hospitals, and teaching vs. nonteaching hospitals. Liver resection (LR),
      pancreaticoduodenectomy, bile duct (BD) resection, and combined liver/BD
      resection were considered more aggressive therapy than BD stent or bypass.
      RESULTS: A total of 32,561 patients with CCA were identified. The proportion
      receiving surgery declined from 36 to 30 %. There was no increase in the
      proportion of LRs or combined liver/BD resection. Patients at HV or teaching
      hospitals were more likely to receive surgical treatment [odds ratio (OR), 1.3, p
      < 0.001; OR, 1.4, p < 0.001]. DISCUSSION: Despite increasing evidence that
      surgical resection increases survival, the number of patients receiving surgery
      has decreased. Although combined liver/BD resection has been advocated as
      standard management for proximal CCA, the practice has not increased. All
      patients with CCA should be considered for assessment at a HV teaching hospital.

PMID- 22847575
TI  - Postoperative intra-abdominal complications assessed by the Clavien-Dindo
      classification following open and laparoscopy-assisted distal gastrectomy for
      early gastric cancer.
AB  - BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been increasingly used for
      the treatment of early gastric cancer, and many advantages over open gastrectomy
      (OG) have been reported. However, only a few reports have assessed postoperative
      complications following LAG using the Clavien-Dindo classification. METHODS: A
      total of 265 patients who underwent distal gastrectomy or pylorus-preserving
      gastrectomy with D1+ lymph node dissection for clinical stage IA early gastric
      cancer at the Shizuoka Cancer Center between June 2009 and December 2011 were
      included in this study. Clinicopathological characteristics and early surgical
      outcomes were compared between patients who underwent LAG (LAG group, n = 129)
      and those who underwent OG (OG group, n = 136). The severity of postoperative
      morbidities was assessed according to the Clavien-Dindo classification. RESULTS:
      There were no differences in sex or age between the two groups. Body mass index
      (21.97 vs. 23.19, P < 0.001) was lower in the LAG group than the OG group. The
      duration of the postoperative hospital stay was similar between the two groups (9
      days each, P = 0.511). There was no difference in the overall morbidity rate
      (grade II or higher) between the two groups (LAG group, 7.0%; OG group, 8.1%; P =
      0.818). The incidence of grade IIIa or more severe morbidities was also not
      significantly different between the LAG group (4.7%) and OG group (2.9%, P =
      0.532). CONCLUSIONS: There was no significant difference in postoperative
      complication rates between the LAG and the OG groups. The more severe Clavien
      Dindo grade III complications, which required surgical interventions, were
      observed at similar rates between the two groups. Laparoscopic gastrectomy for
      early gastric cancer is therefore feasible in terms of the incidence and severity
      of intra-abdominal complications.

PMID- 22847576
TI  - A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal
      recessive osteopetrosis in a Jordanian patient.
AB  - Human malignant autosomal recessive osteopetrosis (ARO) is a genetically
      heterogeneous disorder caused by reduced bone resorption by osteoclasts.
      Mutations in the CLCN7 gene are responsible not only for a substantial portion of
      ARO patients but also for other forms of osteopetrosis characterized by different
      severity and inheritance. The lack of a clear genotype/phenotype correlation
      makes genetic counseling a tricky issue for CLCN7-dependent osteopetrosis. Here,
      we characterize the first homozygous interstitial deletion in 16p13.3, detected
      by array comparative genomic hybridization in an ARO patient of Jordanian origin.
      The deletion involved other genes besides CLCN7, while the proband displayed a
      classic ARO phenotype; however, her early death did not allow more extensive
      clinical investigations. The identification of this novel genomic deletion
      involving a large part of the CLCN7 gene is of clinical relevance, especially in
      prenatal diagnosis, and suggests the possibility that this kind of mutation has
      been underestimated so far. These data highlight the need for alternative
      approaches to genetic analysis also in other ARO-causative genes.

PMID- 22847577
TI  - A solution-processable phosphonate functionalized deep-blue fluorescent emitter
      for efficient single-layer small molecule organic light-emitting diodes.
AB  - Based on a p-type scaffold, a novel solution-processable phosphonate
      functionalized deep-blue fluorescent emitter has been designed and synthesized.
      The corresponding non-doped single-layer SMOLED shows a peak current efficiency
      of 0.76 cd A(-1) with CIE coordinates of (0.15, 0.09), which is about three
      orders of magnitude higher than that of the prototype with tert-butyl
      substituents.

PMID- 22847578
TI  - Prostate-specific antigen screening for prostate cancer and the risk of overt
      metastatic disease at presentation: analysis of trends over time.
AB  - BACKGROUND: The objective of this study was to estimate the total number of
      patients who would be expected to present with metastatic (M1) prostate cancer
      (PC) in the modern US population in a given year if the age-specific and race
      specific annual incidence rates of M1 PC were the same as the rates in the era
      before prostate-specific antigen (PSA) testing. METHODS: The authors computed the
      total number of men who presented with M1 PC in the Surveillance, Epidemiology,
      and End Results (SEER) 9 registries area in the year 2008 (the most recent SEER
      year) and estimated the number of cases that would be expected to occur in this
      area in the year 2008 in the absence of PSA testing. The expected number was
      computed by multiplying each age-race-specific average annual incidence rate from
      the pre-PSA era (1983-1985) by the number of men in the corresponding age-race
      category in the year 2008 and adding the products. RESULTS: In the year 2008, the
      observed and expected numbers of men presenting with M1 PC in the SEER 9
      registries area were 739 and 2277, respectively, with an expected-to-observed
      ratio of 3.1 (95% confidence interval, 3.0-3.2). If this ratio was applied to the
      total US population in the year 2008, then the total number of men presenting
      with M1 PC in that year would be equal to approximately 25,000 instead of the
      approximately 8000 actually observed. CONCLUSIONS: If the pre-PSA era rates were
      present in the modern US population, then the total number of men presenting with
      M1 PC would be approximately 3 times greater than the number actually observed.

PMID- 22847579
TI  - Employer, use of personal protective equipment, and work safety climate: Latino
      poultry processing workers.
AB  - BACKGROUND: This analysis describes the work safety climate of Latino poultry
      processing workers and notes differences by worker personal characteristics and
      employer; describes the use of common personal protective equipment (PPE) among
      workers; and examines the associations of work safety climate with use of common
      PPE. METHODS: Data are from a cross-sectional study of 403 Latino poultry
      processing workers in western North Carolina. RESULTS: Work safety climate
      differed little by personal characteristics, but it did differ consistently by
      employer. Provision of PPE varied; for example, 27.2% of participants were
      provide with eye protection at no cost, 57.0% were provided with hand protection
      at no cost, and 84.7% were provided with protective clothing at no cost. PPE use
      varied by type. Provision of PPE at no cost was associated with lower work safety
      climate; this result was counter-intuitive. Consistent use of PPE was associated
      with higher work safety climate. CONCLUSIONS: Work safety climate is important
      for improving workplace safety for immigrant workers. Research among immigrant
      workers should document work safety climate for different employers and
      industries, and delineate how work safety climate affects safety behavior and
      injuries.

PMID- 22847586
TI  - Lung cancer screening: confession of a skeptic.

PMID- 22847580
TI  - Cytokine genetic profile in Whipple's disease.
AB  - Whipple's disease (WD) is a very rare chronic systemic condition characterised by
      a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma
      whipplei, a bacterium widely diffuse in the environment. To investigate whether
      this Th2/Treg polarised response has a genetic background, we investigated the
      Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks
      to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13
      cytokine genes was analysed in 111 German and 22 Italian patients using the
      polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The
      frequencies of the genotypes, haplotypes and functional phenotypes were compared
      with those obtained in 201 German and 140 Italian controls. Clinical
      heterogeneity was also considered. Functionally, WD patients may be considered as
      low producers of TGF-beta1, having an increased frequency of the genotype TGF
      beta1+869C/C,+915C/C [12.3 % vs. 3.81 %, odds ratio (OR) = 4.131, p = 0.0002] and
      high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34 % vs. 1.17 %, OR
      = 5.09, p = 0.0096). No significant association was found between cytokine
      polymorphism and clinical variability. Analogously to the recent cellular
      findings of a Th2/Treg polarised response, we showed that the cytokine genetic
      profile of WD patients is skewed toward a Th2 and Treg response. This was similar
      in both German and Italian populations. However, the significant deviations
      versus the controls are poorer than that expected on the basis of these recent
      cellular findings.

PMID- 22847587
TI  - Primary care perspective on lung cancer screening.

PMID- 22847588
TI  - Current status of tobacco policy and control.
AB  - Behaviors pertaining to tobacco use have changed significantly over the past
      century. Compared with 1964, smoking prevalence rates have halved from 40% to
      20%, and as a result there has been a slow but steady decline in the rates of
      tobacco-induced diseases such as heart disease and cancer. Growing awareness of
      the health risks of smoking was aided by the US Surgeon Reports that were issued
      on a nearly annual basis starting from 1964. Concerns about the hazards of
      breathing in second-hand smoke further contributed to the declining social
      acceptance of smoking, which evolved into regulatory actions restricting smoking
      on buses, planes, retail outlets, restaurants, and bars. Today, 23 states and 493
      localities have comprehensive laws restricting indoor smoking. This paper
      examines public policies that have made a significant impact on smoking and lung
      cancer rates and discusses potential future research directions to further reduce
      the diseases caused by smoking.

PMID- 22847589
TI  - Establishing a computed tomography screening clinic.
AB  - Since the publication of the National Lung Screening Trial results, there has
      been increasing interest among radiologists to establish computed tomography (CT)
      screening centers. During the past 10 years, we have operated a CT screening
      center in suburban Boston, MA. The purpose of this paper is to describe our
      process for performing self-referred CT lung screening exams, including our
      organizational structure, marketing, patient selection process, and standardized
      workflow. Direct communication between the patient and radiologist, both before
      and after the CT scan, in our opinion, is critical to a successful screening
      program. In many ways, CT screening offers radiologists a wonderful opportunity
      to interact directly with patients. Showing abnormal lung findings to patients on
      their CT scans may help create a unique "teachable" moment for current smokers
      and may help motivate patients to quit smoking.

PMID- 22847590
TI  - Technical parameters and interpretive issues in screening computed tomography
      scans for lung cancer.
AB  - Lung cancer screening computed tomographies (CTs) differ from traditional chest
      CT scans in that they are performed at very low radiation doses, which allow the
      detection of small nodules but which have a much higher noise content than would
      be acceptable in a diagnostic chest CT. The technical parameters require a great
      deal of attention on the part of the user, because inappropriate settings could
      result in either excess radiation dose to the large population of screened
      individuals or in low-quality images with impaired nodule detectability. Both
      situations undermine the main goal of the screening program, which is to detect
      lung nodules using as low a radiation dose as can reasonably be achieved. Once an
      image has been obtained, there are unique interpretive issues that must be
      addressed mainly because of the very high noise content of the images and the
      high prevalence of incidental findings in the chest unrelated to the sought-after
      pulmonary nodules.

PMID- 22847591
TI  - Overview and strategic management of subsolid pulmonary nodules.
AB  - A new classification of lung adenocarcinoma has been proposed recently-the
      International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society classification. Abundant information from
      recent lung cancer computed tomography (CT) screening programs has increased our
      understanding of the strong, although imperfect, correlation between histologic
      findings of lung adenocarcinoma and subsolid pulmonary nodules on CT, including
      both "pure" ground-glass nodules (GGNs) and "part-solid" GGNs. Moreover, serial
      CT imaging has demonstrated stepwise progression of these nodules in a subset of
      patients, characterized by increase in size and density of GGNs and development
      of a solid component. Given the higher incidence of malignancy and the
      considerably lower growth rate of subsolid nodules, dedicated standardized
      guidelines for management of these nodules have been proposed, including long
      term (>=3 y) CT follow-up using a low-dose technique. Radiologists should be
      familiar with the new terminology of lung adenocarcinomas and strategic
      management of subsolid pulmonary nodules.

PMID- 22847592
TI  - Review of ACR Appropriateness Criteria(r) Radiologic Management of Thoracic
      Nodules and Masses.
AB  - This manuscript is a review of the recently published ACR Appropriateness
      Criteria Radiologic Management of Thoracic Nodules and Masses. Presented are best
      practice guidelines for the imaging evaluation and biopsy recommendations for
      pulmonary nodules, mediastinal masses, and pleural abnormalities. The American
      College of Radiology Appropriateness Criteria are evidence-based guidelines for
      specific clinical conditions that are reviewed every 2 years by a
      multidisciplinary expert panel. The guideline development and review include an
      extensive analysis of current medical literature from peer-reviewed journals and
      the application of a well-established consensus methodology (modified Delphi) to
      rate the appropriateness of imaging and treatment procedures by the panel. In
      those instances in which evidence is lacking or not definitive, expert opinion
      may be used to recommend imaging or treatment.

PMID- 22847594
TI  - Systolic anterior motion of the mitral valve.

PMID- 22847595
TI  - Fine-tuning device performances of small molecule solar cells via the more
      polarized DPP-attached donor units.
AB  - Three solution-processable small molecules of DPPT, DPPSe and DPPTT were
      synthesized by Stille coupling through attaching donor units of thiophene (T),
      selenophene (Se) and thieno[3,2-b]thiophene (TT) to the diketopyrrolopyrrole
      (DPP) core, respectively. Replacement of the T donors with the more polarized Se
      units results in a balance between the a and b direction packing and an obvious
      increase of the power conversion efficiency (PCE) from 1.90% to 2.33% with the
      increase of the short-circuit current (I(sc)) from 5.59 to 5.81 mA cm(-2) and the
      open-circuit voltage (V(oc)) from 0.78 V to 0.86 under the small
      molecule/acceptor ratio of 3 : 1. However, introduction of the conjugation
      enlarged TT groups (versus the T units) leads to a decrease of the PCE, down to
      1.70%, with a significant decrease of the fill factor (FF) (38% versus 44%), due
      to its poor film-forming characteristics.

PMID- 22847596
TI  - Measuring and modeling attentional dwell time.
AB  - Attentional dwell time (AD) defines our inability to perceive spatially separate
      events when they occur in rapid succession. In the standard AD paradigm, subjects
      should identify two target stimuli presented briefly at different peripheral
      locations with a varied stimulus onset asynchrony (SOA). The AD effect is seen as
      a long-lasting impediment in reporting the second target, culminating at SOAs of
      200-500 ms. Here, we present the first quantitative computational model of the
      effect--a theory of temporal visual attention. The model is based on the neural
      theory of visual attention (Bundesen, Habekost, & Kyllingsbaek, Psychological
      Review, 112, 291-328 2005) and introduces the novel assumption that a stimulus
      retained in visual short-term memory takes up visual processing-resources used to
      encode stimuli into memory. Resources are thus locked and cannot process
      subsequent stimuli until the stimulus in memory has been recoded, which explains
      the long-lasting AD effect. The model is used to explain results from two
      experiments providing detailed individual data from both a standard AD paradigm
      and an extension with varied exposure duration of the target stimuli. Finally, we
      discuss new predictions by the model.

PMID- 22847597
TI  - Enhanced recognition of words previously presented in a task with nonfocal
      prospective memory requirements.
AB  - Remembering to perform deferred actions when events are encountered in the future
      is referred to as event-based prospective memory. Individuals can be slower to
      respond to ongoing tasks when they have prospective memory task requirements.
      These costs are interpreted as evidence for cognitive control processes allocated
      to the prospective memory task, but we know little about these processes. In the
      present article, the recognition of nontargets previously presented in an ongoing
      task with prospective memory task requirements provided evidence for the
      differential processing of individual ongoing task items. Participants performed
      a lexical decision task, where some participants were required to make an
      alternative prospective memory response either to a specific word (focal) or to
      exemplars of a category (nonfocal). Participants were slower to respond to the
      ongoing task in the nonfocal conditions than in the control condition (costs),
      regardless of whether or not prospective memory task importance was emphasized.
      Participants were also slower to respond to the ongoing task in the focal
      conditions than in the control condition, but only when prospective memory task
      importance was emphasized. This task was followed by a surprise recognition
      memory test in which nontarget words from the lexical decision task were
      intermixed with new words. Focal conditions, but not nonfocal conditions, showed
      better discrimination on the recognition task, as compared with the control
      condition. Participants in nonfocal conditions mapped the semantic features of
      the ongoing task letter strings onto the semantic features of their prospective
      memory category, and this elaboration in the processing of individual nontargets
      increased incidental learning and produced the recognition benefit.

PMID- 22847599
TI  - TPO-receptor agonists in ITP: a clinician's navigation between Scylla and
      Charybdis.

PMID- 22847600
TI  - Eccentric training improves tendon biomechanical properties: a rat model.
AB  - The treatment of choice for tendinopathies is eccentric reeducation. Although the
      clinical results appear favorable, the biomechanical changes to the tissue are
      not yet clear. Even if the mechanotransduction theory is commonly accepted, the
      physiology of tendons is not clearly understood. We aimed to better define the
      biomechanical and histological changes that affect healthy tendon after eccentric
      and concentric training. This study compared the effects of two methods of
      training (eccentric [E] training and concentric [C] training) with untrained (U)
      rats. The animals were trained over a period of 5 weeks. The tricipital,
      patellar, and Achilles tendons were removed, measured and a tensile test until
      failure was performed. A histological analysis (hematoxylin and eosin and
      Masson's trichrome stains) was also realized. There was a significant increase in
      the rupture force of the patellar and tricipital tendons between the U and E
      groups. The tricipital tendons in the control group presented a significantly
      smaller cross-sectional area than the E- and C-trained groups, but none was
      constated between E and C groups. No significant difference was observed for the
      mechanical stress between the three groups for all three tendons. Histological
      studies demonstrated the development of a greater number of blood vessels and a
      larger quantity of collagen in the E group. The mechanical properties of tendons
      in rats improve after specific training, especially following eccentric training.
      Our results partly explained how mechanical loading, especially in eccentric
      mode, could improve the healing of tendon.

PMID- 22847601
TI  - Prognostic value of Twist and E-cadherin in patients with osteosarcoma.
AB  - Twist, a basic helix-loop-helix transcription factor, and E-cadherin are both
      correlated with the metastatic progression of several types of cancer. However,
      it is currently unknown whether their activations have relevance to the
      progression of osteosarcoma. The purpose of the present study was to investigate
      the clinicopathological and prognostic value of Twist and E-cadherin in
      osteosarcoma. Twist and E-cadherin expressions were determined by
      immunohistochemistry. Patient survival rates were determined by Kaplan-Meier
      method and log-rank test. Cox regression was adopted for multivariate analysis of
      prognostic factors. The positive rates of Twist and E-cadherin in 107
      osteosarcoma specimens were 31.8 % (34/107) and 20.6 % (22/107), respectively.
      Twist expression was significantly correlated with that of E-cadherin (r = 
      0.209, P = 0.031). The positive expression of Twist and E-cadherin was
      significantly associated with metastasis in 107 osteosarcoma specimens (both P <
      0.05). Patients with positive Twist expression had significantly poorer overall
      survival (OS; P < 0.05) and disease-free survival (DFS, P < 0.05) when compared
      with patients with the negative expression of Twist. Patients with positive
      expression of E-cadherin had significantly poorer OS (P < 0.05) when compared
      with patients with negative E-cadherin expression, but not a significantly poorer
      DFS (P = 0.081). On multivariate analysis, Twist expression and age were found to
      be independent prognostic factors for OS (both P < 0.05) and DFS (both P < 0.05).
      Our results suggest that Twist was expressed significantly more and E-cadherin
      significantly less in osteosarcoma with metastasis, and expression of both might
      be related to the prediction of metastasis potency and poor prognosis for
      patients with osteosarcoma.

PMID- 22847602
TI  - Injection drug users trained by overdose prevention programs: responses to
      witnessed overdoses.
AB  - In response to the growing public health problem of drug overdose, community
      based organizations have initiated overdose prevention programs (OPPs), which
      distribute naloxone, an opioid antagonist, and teach overdose response
      techniques. Injection drug users (IDUs) have been targeted for this intervention
      due to their high risk for drug overdose. Limited research attention has focused
      on factors that may inhibit or prevent IDUs who have been trained by OPPs to
      undertake recommended response techniques when responding to a drug overdose.
      IDUs (n = 30) trained by two OPPs in Los Angeles were interviewed in 2010-2011
      about responses to their most recently witnessed drug overdose using an
      instrument containing both open and closed-ended questions. Among the 30
      witnessed overdose events, the victim recovered in 29 cases while the outcome was
      unknown in one case. Participants responded to overdoses using a variety of
      techniques taught by OPPs. Injecting the victim with naloxone was the most
      commonly recommended response while other recommended responses included
      stimulating the victim with knuckles, calling 911, and giving rescue breathing.
      Barriers preventing participants from employing recommended response techniques
      in certain circumstances included prior successes using folk remedies to revive a
      victim, concerns over attracting police to the scene, and issues surrounding
      access to or use of naloxone. Practical solutions, such as developing booster
      sessions to augment OPPs, are encouraged to increase the likelihood that trained
      participants respond to a drug overdose with the full range of recommended
      techniques.

PMID- 22847603
TI  - Synthesis of (Z)-3-aryloxy-acrylonitriles, (E)-3-aryloxy-acrylonitriles and 3
      cyanobenzofurans through the sequential reactions of phenols with
      propiolonitriles.
AB  - A Na(2)CO(3)-promoted addition of phenols to propiolonitriles generated (Z)-3
      aryloxy-acrylonitriles in nearly quantitative yields with exclusively Z-isomers,
      and a DABCO-promoted addition reaction of phenols with propiolonitriles afforded
      mainly (E)-3-aryloxy-acrylonitriles with high yields. The obtained (E)-3-aryloxy
      acrylonitriles underwent intramolecular cyclization to give 3-cyanobenzofurans in
      good yields through palladium-catalyzed direct C-H bond functionalization.

PMID- 22847604
TI  - 20/20--Alcohol and age-related macular degeneration: the Melbourne Collaborative
      Cohort Study.
AB  - Little evidence exists regarding associations between age-related macular
      degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or
      different types of alcoholic beverage. The authors examined associations between
      AMD prevalence and alcohol intake using 20,963 participants from the Melbourne
      Collaborative Cohort Study aged 40-69 years at baseline (1990-1994).
      Participants' alcohol consumption was determined from a structured interview at
      baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes
      were taken and evaluated for early and late AMD signs. Drinking more than 20 g of
      alcohol per day was associated with an approximate 20% increase in the odds of
      early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004)
      when compared with those who reported no alcohol intake at baseline, having
      adjusted for sex, age, smoking, country of birth, education, physical activity,
      and energy from food. This positive association was apparent for wine, beer, and
      spirits. The estimates were similar for both sexes. The odds ratio for those
      drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence
      interval: 0.85, 2.45; P = 0.17). These results show a modest association between
      alcohol consumption and increased AMD risk.

PMID- 22847605
TI  - Bolus injection of newly synthesized vitamin E derivative ETS-GS for the
      treatment of acute severe ulcerative colitis in a mouse model. New vitamin E
      derivative for acute severe UC.
AB  - PURPOSE: Vitamin E with its antioxidant action has therapeutic effects on
      ulcerative colitis (UC), but use of vitamin E is limited because of its
      insolubility in water. We developed ETS-GS (gamma-L-glutamyl-S-[2-[[[3,4-dihydro
      2,5,7,8-tetramethyl-2-(4,8,12-trimethyltri-decyl)-2 H-1-benzopyran-6
      yl]oxy]carbonyl]-3-oxo-3-[(2-sulfoethyl)amino]propyl]-L-cysteinylglycine sodium
      salt), a newly synthesized soluble vitamin E derivative with strong antioxidant
      action. We evaluated the therapeutic effects of bolus injection of ETS-GS on
      acute severe UC in a mouse model. METHODS: An animal model of acute severe UC was
      induced by feeding mice 5 % dextran sulfate sodium (DSS) for 5 days, followed by
      1 % DSS on days 5-8, the experimental period. ETS-GS or saline was administered
      by subcutaneous bolus injection during the experimental period. We examined
      disease activity index (DAI) score, histological score, colon length, colon
      weight, and serum cytokines in the mice. RESULTS: The following results at day 8
      in the DSS + ETS-GS group were significantly lower than those in the DSS + Saline
      group: DAI score, 2.6 +/- 0.6 vs. 3.1 +/- 0.5; histological score, 2.1 +/- 1.0
      vs. 3.1 +/- 0.8; serum interleukin (IL)-6, 15 +/- 9.4 vs. 39 +/- 23 pg/ml; and
      keratinocyte-derived chemokine (KC), 122 +/- 61 vs. 228 +/- 66 pg/ml (P < 0.05).
      Colon length, colon weight, and serum IL-10 in the DSS + ETS-GS group were
      significantly higher than those in the DSS + Saline group (88 +/- 12 vs. 75 +/-
      5.7 mm, 0.48 +/- 0.09 vs. 0.38 +/- 0.05 g, and 55 +/- 18 vs. 31 +/- 10 pg/ml,
      respectively; P < 0.05). CONCLUSIONS: Bolus injection of ETS-GS may be one
      therapeutic modality for acute severe UC. Its effects are associated with
      suppression of serum IL-6 and serum KC and promotion of serum IL-10.

PMID- 22847606
TI  - Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and
      prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for
      locally advanced rectal cancer.
AB  - PURPOSE: We investigated the relationships between biomarkers related to
      anaerobic glycolytic metabolism (GLUT1, LDH5, PDK1, and HIF-1alpha proteins),
      pathologic response, and prognosis. METHODS: All stage II and stage III rectal
      cancer patients had 50.4 Gy (1.8 Gy/day in 28 fractions) over 5.5 weeks, plus 5
      fluorouracil (425 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to
      5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of
      all therapies. Expression of GLUT1, LDH5, PDK1, and HIF-1alpha proteins was
      determined by immunohistochemistry and was assessed in 104 patients with rectal
      cancer treated with neoadjuvant chemoradiotherapy. RESULTS: This study included
      stage II and III rectal cancer patients, and each stage accounted for each 50 %
      of the total cases. A high expression of GLUT1 protein was associated with a
      significantly lower rate of ypCR compared with low expression of GLUT1 protein
      (4.0 % vs. 27.8 %, respectively; p = 0.012). GLUT1 expression was also
      significantly higher in the poor response group (Grade 0, 1) than in the good
      response group (Grade 2, 3) (34.0 % vs. 14.8 %, respectively; p = 0.022). In
      recurrence analysis, the expression of GLUT1 protein demonstrated a significant
      correlation with time to recurrence, based on a log-rank method (p = 0.016). When
      analyzed by multiple Cox regression, the positive expression of GLUT1 was the
      most significant and independent unfavorable prognostic factor (p = 0.004).
      CONCLUSIONS: GLUT1 expression is a predictive and prognostic factor for
      pathologic complete response and recurrence in rectal cancer patients treated
      with 5-flurouracil and leucovorin neo-adjuvant chemoradiotherapy.

PMID- 22847607
TI  - Lower whole blood selenium level is associated with higher operative risk and
      mortality following cardiac surgery.
AB  - PURPOSE: The authors intended to test their hypothesis that a low blood selenium
      level is associated with higher mortality, morbidity, and increased inflammatory
      response following cardiac surgery. METHODS: A single-center clinical survey was
      conducted on 197 consecutive patients undergoing on-pump operation in Debrecen,
      Hungary. Blood samples for whole blood selenium analysis were taken immediately
      before the surgery. Their risk profiles were evaluated according to the
      EuroSCORE. The outcome parameters were as follows: 30-day mortality, incidence of
      systemic inflammatory response syndrome, and cardiac and renal dysfunction. The
      main laboratory outcome variables were the postoperative concentrations of C
      reactive protein and cardiac troponin I. RESULTS: The mean blood selenium level
      was significantly lower in non-survivors 102.2 +/- 19.5 MUg/L compared with
      survivors 111.1 +/- 16.9 MUg/L (p = 0.047), and the mean age, EuroSCORE values,
      and troponin concentrations were significantly higher in the non-survivors. To
      exclude these potential confounders a logistic regression model was fitted to our
      data, with mortality as the outcome and the EuroSCORE, the degree of troponin
      elevation, and selenium concentration as explanatory variables. This model
      revealed that a lower selenium level was a minor but apparently existing risk
      factor for postoperative mortality. CONCLUSION: Further examinations are required
      to clarify the question that remained unanswered in this study: the role of low
      selenium in the causality chain leading to higher postoperative mortality.

PMID- 22847608
TI  - Anesthetic management for a patient with very-long-chain acyl-coenzyme A
      dehydrogenase deficiency.

PMID- 22847609
TI  - The valence and Rydberg excited states of CH2: a theoretical exploration.
AB  - Using the completed active space second-order perturbation (CASPT2) method,
      valence and Rydberg excited states of CH(2) molecule are probed with the large
      atomic natural orbital (ANO-L) basis set. Five states are optimized and the
      geometric parameters are in good agreement with the available data in
      literatures, furthermore, the state of 2(1)B(1) is obtained for the first time.
      Valence and Rydberg excited states of CH(2) are also calculated for the vertical
      transitions with the ANO-L+ basis set that is constructed by adding a set of
      1s1p1d Rydberg orbitals into the ANO-L basis set. Two Rydberg states of the
      p(~3)A(2) and r(~3) B(1) at 9.88 and 10.50 eV are obtained for the first time,
      and the 3a(1) -> 3d(yz) nature of the state p(~3)A(2) and the 3a(1) -> d(x2-y2)
      nature of the state r(~3)B(1) are confirmed.

PMID- 22847610
TI  - Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma.
AB  - WEE1 kinase has been described as a major gate keeper at the G2 cell cycle
      checkpoint and to be involved in tumour progression in different malignant
      tumours. Here we analysed the expression levels of WEE1 in a series of melanoma
      patient samples and melanoma cell lines using immunoblotting, quantitative real
      time PCR and immunohistochemistry. WEE1 expression was significantly
      downregulated in patient samples of metastatic origin as compared with primary
      melanomas and in melanoma cell lines of high aggressiveness as compared with cell
      lines of low aggressiveness. Moreover, there was an inverse correlation between
      the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses
      showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1
      mRNA and protein expression in these cells. Reporter gene analysis confirmed
      direct targeting of the WEE1 3' untranslated region (3'UTR) by miR-195.
      Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1
      reduction and significantly reduced stress-induced G2-M cell cycle arrest, which
      could be restored by stable overexpression of WEE1. Moreover, miR-195
      overexpression and WEE1 knockdown, respectively, increased melanoma cell
      proliferation. miR-195 overexpression also enhanced migration and invasiveness of
      melanoma cells. Taken together, the present study shows that WEE1 expression in
      malignant melanoma is directly regulated by miR-195. miR-195-mediated
      downregulation of WEE1 in metastatic lesions may help to overcome cell cycle
      arrest under stress conditions in the local tissue microenvironment to allow
      unrestricted growth of tumour cells. 

PMID- 22847611
TI  - MiR-181a confers resistance of cervical cancer to radiation therapy through
      targeting the pro-apoptotic PRKCD gene.
AB  - The purpose of this study was to define the roles of miR-181a in determining
      sensitivity of cervical cancer to radiation therapy, to explore the underlying
      mechanism and to evaluate the potential of miR-181a as a biomarker for predicting
      radio-sensitivity. Tumor specimens from 18 patients with a histological diagnosis
      of squamous cervical carcinoma (stage IIIB) were used in the micro-RNA profiling
      and comparison. These patients never received any chemotherapy before radiation
      therapy. Human cervical cancer cell lines, SiHa and Me180, were used in vitro
      (cell culture) and in vivo (animal) studies. Transfection of tumor cells with the
      mimic or inhibitor of miR-181a, and reporter gene assay, were performed to
      investigate the role of miR-181a in determining radio-sensitivity and the target
      gene. Higher expression of miR-181a was observed in human cervical cancer
      specimens and cell lines that were insensitive to radiation therapy, as compared
      with sensitive cancer specimens and the cell lines. We also found that miR-181a
      negatively regulated the expression of PRKCD, a pro-apoptotic protein kinase, via
      targeting its 3'-untranslated region (UTR), thereby inhibiting irradiation
      induced apoptosis and decreasing G2/M block. The role of miR-181a in conferring
      cellular resistance to radiation treatment was validated both in cell culture
      models and in mouse tumor xenograft models. The effect of miR-181a on radio
      resistance was mediated through targeting the 3'-UTR of PRKCD gene. Thus, the
      expression level of miR-181a in cervical cancer may serve as a biomarker for
      sensitivity to radiation therapy, and targeting miR-181a may represent a new
      approach to sensitizing cervical cancer to radiation treatment.

PMID- 22847612
TI  - Bach1 is critical for the transformation of mouse embryonic fibroblasts by
      Ras(V12) and maintains ERK signaling.
AB  - Reactive oxygen species (ROS), by-products of aerobic respiration, promote
      genetic instability and contribute to the malignant transformation of cells.
      Among the genes related to ROS metabolism, Bach1 is a repressor of the oxidative
      stress response, and a negative regulator of ROS-induced cellular senescence
      directed by p53 in higher eukaryotes. While ROS are intimately involved in
      carcinogenesis, it is not clear whether Bach1 is involved in this process. We
      found that senescent Bach1-deficient mouse embryonic fibroblasts (MEFs) underwent
      spontaneous immortalization the same as did the wild-type cells. When transduced
      with constitutively active Ras (H-Ras(V12)), the proliferation and colony
      formation of these cells in vitro were markedly reduced. When transplanted into
      athymic nude mice, the growth and vascularization of tumors derived from Bach1
      deficient cells were also decreased. Gene expression profiling of the MEFs
      revealed a new H-Ras(V12) signature, which was distinct from the previously
      reported signatures in epithelial tumors, and was partly dependent on Bach1. The
      Bach1-deficient cells showed diminished phosphorylation of MEK and ERK1/2 in
      response to H-Ras(V12), which was consistent with the alterations in the gene
      expression profile, including phosphatase genes. Finally, Bach1-deficient mice
      were less susceptible to 4-nitroquinoline-1-oxidide (4-NQO)-induced tongue
      carcinoma than wild-type mice. Our data provide evidence for a critical role of
      Bach1 in cell transformation and tumor growth induced by activated H-Ras(V12). 

PMID- 22847614
TI  - Selection for Evi1 activation in myelomonocytic leukemia induced by hyperactive
      signaling through wild-type NRas.
AB  - Activation of NRas signaling is frequently found in human myeloid leukemia and
      can be induced by activating mutations as well as by mutations in receptors or
      signaling molecules upstream of NRas. To study NRas-induced leukemogenesis, we
      retrovirally overexpressed wild-type NRas in a murine bone marrow transplantation
      (BMT) model in C57BL/6J mice. Overexpression of wild-type NRas caused
      myelomonocytic leukemias ~3 months after BMT in the majority of mice. A subset of
      mice (30%) developed malignant histiocytosis similar to mice that received
      mutationally activated NRas(G12D)-expressing bone marrow. Aberrant Ras signaling
      was demonstrated in cells expressing mutationally active or wild-type NRas, as
      increased activation of Erk and Akt was observed in both models. However, more
      NRas(G12D) were found to be in the activated, GTP-bound state in comparison with
      wild-type NRas. Consistent with observations reported for primary human
      myelomonocytic leukemia cells, Stat5 activation was also detected in murine
      leukemic cells. Furthermore, clonal evolution was detected in NRas wild-type
      induced leukemias, including expansion of clones containing activating vector
      insertions in known oncogenes, such as Evi1 and Prdm16. In vitro cooperation of
      NRas and Evi1 improved long-term expansion of primary murine bone marrow cells.
      Evi1-positive cells upregulated Bcl-2 and may, therefore, provide anti-apoptotic
      signals that collaborate with the NRas-induced proliferative effects. As
      activation of Evi1 has been shown to coincide with NRAS mutations in human acute
      myeloid leukemia, our murine model recapitulates crucial events in human
      leukemogenesis.

PMID- 22847615
TI  - Physical workloads of the upper-extremity among workers of the Colombian flower
      industry.
AB  - BACKGROUND: We report the prevalence of symptoms of common upper-limb disorders
      and describe comprehensively mechanical workloads in a sample of workers of the
      Colombian flower industry. METHODS: One hundred fifty eight workers from eight
      flower manufacturers were assessed. Assessments included Borg self-reported
      exertion and working practices, medical examinations, video-based observations
      and kinematic and surface muscular activity assessments of upper-limb. RESULTS:
      Point prevalence of signs and symptoms of CTS, epicondylitis, and De Quervain's
      disease was 32.9%, 15.2%, and 13.3%, respectively. All tasks are executed on
      average in wrist extension, ulnar deviation, and high elbow flexion. Average
      median muscle activity across tasks ranged between 3.6% and 27.3%. Forearm
      muscles were mainly active. CONCLUSIONS: The occurrence of signs and symptoms of
      upper-extremity musculoskeletal disorders was high among the sample. The
      classification and cutting task showed the highest mechanical demands.
      Interventions in this working population are required and should be directed to
      allow for muscular rest on regular basis.

PMID- 22847616
TI  - High-density assembly of gold nanoparticles with zwitterionic carbon nanotubes
      and their electrocatalytic activity in oxygen reduction reaction.
AB  - Gold nanoparticles (AuNPs) were assembled with high density onto multi-walled
      carbon nanotubes, which were functionalized with zwitterionic
      poly(imidazoliumsulfonate). The AuNP/zwitterionic CNT hybrids exhibited decent
      electrocatalytic activity in oxygen reduction reaction as the AuNP-based
      catalysts.

PMID- 22847613
TI  - Mutant p53 gain-of-function induces epithelial-mesenchymal transition through
      modulation of the miR-130b-ZEB1 axis.
AB  - The tumor suppressor gene p53 has been implicated in the regulation of epithelial
      mesenchymal transition (EMT) and tumor metastasis by regulating microRNA (miRNA)
      expression. Here, we report that mutant p53 exerts oncogenic functions and
      promotes EMT in endometrial cancer (EC) by directly binding to the promoter of
      miR-130b (a negative regulator of ZEB1) and inhibiting its transcription. We
      transduced p53 mutants into p53-null EC cells, profiled the miRNA expression by
      miRNA microarray and identified miR-130b as a potential target of mutant p53.
      Ectopic expression of p53 mutants repressed the expression of miR-130b and
      triggered ZEB1-dependent EMT and cancer cell invasion. Loss of an endogenous p53
      mutation increased the expression of miR-130b, which resulted in reduced ZEB1
      expression and attenuation of the EMT phenotype. Furthermore, re-expression of
      miR-130b suppressed mutant p53-induced EMT and ZEB1 expression. Importantly, the
      expression of miR-130 was significantly reduced in EC tissues, and patients with
      higher expression levels of miR-130b survived longer. These data provide a novel
      understanding of the roles of p53 gain-of-function mutations in accelerating
      tumor progression and metastasis through modulation of the miR-130b-ZEB1 axis. 

PMID- 22847617
TI  - Demographic diversity, communication and learning behaviour in healthcare groups.
AB  - An integrative model of group learning was tested in a sample of 40 healthcare
      groups (434 respondents), and the results show that age diversity reduces the
      frequency of face-to-face communication whereas educational diversity reduces the
      frequency of virtual communication in healthcare groups. Frequency of
      communication (both face-to-face and virtual), in turn, positively impacts on the
      emergence of trust and psychological safety, which are essential drivers of
      learning behaviours in healthcare groups. Additional results show that average
      educational achievement within groups is conducive for communication frequency
      (both face-to-face and virtual), whereas mean age within groups has a negative
      association with the use of virtual communication in healthcare groups.

PMID- 22847618
TI  - Carboxylesterase 1 (CES1) genetic polymorphisms and oseltamivir activation.

PMID- 22847619
TI  - Concurrent use of tramadol and oral vitamin K antagonists and the risk of
      excessive anticoagulation: a register-based nested case-control study.
AB  - OBJECTIVES: The objective was to assess whether the concurrent use of tramadol
      and vitamin K antagonists (VKAs) leads to an increased risk of excessive
      anticoagulation. DESIGN: The study was designed as a case-control study, nested
      within users of VKA and with tramadol use as our main exposure. We used
      conditional logistic regression to control for potential confounders. SETTING:
      Prescription data from primary care were obtained from Odense
      Pharmacoepidemiological Database (OPED). Information about hospital admissions
      was obtained from the patient administrative system of Funen County (FPAS).
      SUBJECTS: Both cases and controls were selected from users of VKA. Cases were
      defined by being hospitalised with a main diagnosis indicating excessive
      anticoagulation. For each case, we selected 15 controls among VKA users, matched
      by age and sex. MAIN OUTCOME MEASURE: Odds ratio for experiencing excessive
      anticoagulation attributable to the use of tramadol. RESULTS: A total of 178
      patients were included, 30 of which were exposed to tramadol, along with 2643
      controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for
      experiencing excessive anticoagulation during use of tramadol was 3.1 (1.9-5.2).
      This corresponds to, on average, one excess case per 250 treatment years (CI 125
      584). The result is potentially confounded by concomitant paracetamol use and the
      presence of acute illness. CONCLUSION: Caution is advised when using tramadol in
      patients using VKA, and if possible, an alternative pain-medication should be
      used.

PMID- 22847620
TI  - "Stealth" alerts to improve warfarin monitoring when initiating interacting
      medications.
AB  - BACKGROUND: As electronic health records (EHRs) become widely adopted, alerts and
      reminders can improve medication safety, but excessive alerts may irritate or
      overwhelm clinicians, thereby reducing their effectiveness. We developed a novel
      "stealth" alert in an EHR to improve anticoagulation monitoring for patients
      prescribed a medication that could interact with warfarin. Instead of alerting
      the prescribing provider, the system notified a multidisciplinary anticoagulation
      management service, so that the prescribing clinicians never saw the alerts. We
      aimed to determine whether these "stealth" alerts increased the frequency of
      anticoagulation monitoring following the co-prescription of warfarin and a
      potentially interacting medication. METHODS: We conducted a pre-post intervention
      study, analyzed using an interrupted time-series, within a large, multispecialty
      group practice that uses a common EHR. The study included a 12-month period
      preceding the intervention, a 2-month period during intervention implementation,
      and a 6-month post-intervention period. The primary outcome measure was the
      proportion of patients completing anticoagulation monitoring within 5 days of a
      new co-prescribing event. RESULTS: Prior to implementation of the stealth alert,
      34 % of patients completed anticoagulation monitoring within 5 days after the
      prescription of a medication with a potential warfarin interaction. After
      implementation of the alert, 39 % completed testing within 5 days (odds ratio
      1.24, 95 % confidence interval 1.12-1.37). CONCLUSIONS: Stealth alerts increased
      the proportion of patients who underwent anticoagulation monitoring following the
      prescription of a medication that could potentially interact with warfarin. This
      team-based approach to clinical-decision support directs alerts away from
      prescribing clinicians and toward individuals who can directly implement them.

PMID- 22847626
TI  - Synaptic defects in type I spinal muscular atrophy in human development.
AB  - Childhood spinal muscular atrophy is an autosomal recessive neuromuscular
      disorder caused by alterations in the Survival Motor Neuron 1 gene that triggers
      degeneration of motor neurons within the spinal cord. Spinal muscular atrophy is
      the second most common severe hereditary disease of infancy and early childhood.
      In the most severe cases (type I), the disease appears in the first months of
      life, suggesting defects in fetal development. However, it is not yet known how
      motor neurons, neuromuscular junctions, and muscle interact in the neuropathology
      of the disease. We report the structure of presynaptic and postsynaptic apparatus
      of the neuromuscular junctions in control and spinal muscular atrophy prenatal
      and postnatal human samples. Qualitative and quantitative data from confocal and
      electron microscopy studies revealed changes in acetylcholine receptor
      clustering, abnormal preterminal accumulation of vesicles, and aberrant
      ultrastructure of nerve terminals in the motor endplates of prenatal type I
      spinal muscular atrophy samples. Fetuses predicted to develop milder type II
      disease had a similar appearance to controls. Postnatal muscle of type I spinal
      muscular atrophy patients showed persistence of the fetal subunit of
      acetylcholine receptors, suggesting a delay in maturation of neuromuscular
      junctions. We observed that pathology in the severe form of the disease starts in
      fetal development and that a defect in maintaining the initial innervation is an
      early finding of neuromuscular dysfunction. These results will improve our
      understanding of the spinal muscular atrophy pathogenesis and help to define
      targets for possible presymptomatic therapy for this disease.

PMID- 22847627
TI  - Validation of a multiplex reverse transcriptase PCR ELISA for the detection of 19
      respiratory tract pathogens.
AB  - INTRODUCTION: Since acute respiratory tract infections inflict a high burden of
      disease in children worldwide, a multiplex reverse transcription polymerase chain
      reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) to detect
      19 different respiratory pathogens was developed and validated. METHODS: A total
      of 430 respiratory specimens were retrospectively tested in parallel by both the
      advanced 19-valent m-RT-PCR-ELISA as well as by culture or individual RT-PCR
      assays used in clinical routine. RESULTS: The mean (median) sensitivity of the m
      RT-PCR-ELISA in the retrospective test was 93.3% (95.1%; range 83.3-100 %), and
      the mean (median) specificity was 99.8 and 100 % (range 98.6-100 %),
      respectively. The mean positive predictive value was 99.3 % (range 93.4-100 %)
      and the mean negative predictive value was 95.3 % (range 98.4-100 %). Feasibility
      and clinical value of the 19-valent method was prospectively shown on 16,231
      incoming clinical specimens from patients between 0 and 16 years of age with
      acute respiratory tract infections admitted to pediatric hospitals or private
      practices from October 2003 to June 2010 in three regions in Germany (Kiel,
      Mainz, Freiburg; Freiburg to June 2007 only). At least one microorganism was
      detected in 10,765 of 16,231 (66.3 %) clinical specimens: 5,044 RV, 1,999 RSV,
      1,286 AV, 944 EV, 737 seasonal IVA, 173 pandemic IVA H1N1-2009, 899 MPV, 518 CV,
      383 PIV3, 268 PIV1, 259 Mpn, 205 IVB, 164 PIV2, 144 PIV4, 103 Bp, 29 Cpn and 29
      Bpp, while reovirus and Lpn were not present in these specimens from a pediatric
      population. More than one organism could be detected in 13.4 % of the specimens.
      CONCLUSIONS: The m-RT-PCR-ELISA evaluated here improves the spectrum for
      diagnosing respiratory infections and is a feasible instrument for individual
      diagnostic and epidemiological studies.

PMID- 22847628
TI  - Effect of short-term school closures on the H1N1 pandemic in Japan: a comparative
      case study.
AB  - PURPOSE: The 2009 worldwide influenza A/H1N1 pandemic particularly affected
      younger people, including schoolchildren. We assessed the effects of class/school
      closure during the pandemic on the spread of H1N1 infection in Japan. METHODS: We
      prospectively monitored 2,141 schoolchildren in 57 classes at two elementary
      schools and two junior high schools in Japan, and evaluated the effects of
      class/school closures on the spread of H1N1 using descriptive epidemiological
      methods. RESULTS: The cumulative rate of H1N1 infection among these children was
      40.9% (876 children). There was a total of 53 closures of 40 classes, including
      school closures, during the pandemic. Time-course changes in the epidemic curve
      showed that school closure reduced the following epidemic peak more than class
      closure. A Poisson regression model showed that a longer duration of closure was
      significantly related to decreased H1N1 occurrence after the resumption of
      classes. CONCLUSIONS: School closure more effectively inhibits subsequent
      epidemic outbreaks than class closure. Longer school closures are effective in
      reducing the spread of infection, and school closure should be implemented as
      early as possible.

PMID- 22847629
TI  - Colonoscopic versus nasogastric fecal transplantation for the treatment of
      Clostridium difficile infection: a review and pooled analysis.
AB  - BACKGROUND: Fecal microbiota transplantation (FMT) has been demonstrated to be
      highly effective for the treatment of recurrent Clostridium difficile infection
      (CDI). However, the best route of administration has not been established. We
      present a pooled analysis of the reported cases of CDI treated with FMT via
      colonoscopy or nasogastric tube (NGT) to evaluate treatment efficacy. METHODS:
      PubMed was searched for English-written articles published up to December 2011.
      Studies that reported cases of FMT for recurrent CDI using either colonoscopy or
      NGT-guided fecal infusion were reviewed. RESULTS: A total of 182 patients from 12
      published studies were identified; 148 patients received FMT via colonoscopy
      (colonoscopy group) and 34 patients received FMT via NGT (NGT group). The median
      age in the colonoscopy group as compared with the NGT group was 72 and 82 years,
      respectively. There were differences regarding pre-FMT treatment for CDI; 134
      patients (90.5 %, 134/148) received lavage with/without antibiotic in the
      colonoscopy group and 34 patients (100.0 %, 34/34) received antibiotic without
      lavage in the NGT group, P < 0.001. A higher stool volume was used for FMT in the
      colonoscopy group (121 patients, 81.8 %, used 100-400 ml) than in the NGT group
      (33 patients, 97.0 %, used <100 ml), P < 0.001. The treatment efficacy did not
      differ significantly; 93.2 % (138/148) success for the colonoscopy group as
      compared to 85.3 % success (29/34) for the NGT group, P = 0.162. Recurrence of
      CDI after FMT was also similar in both the colonoscopy group (8/148 5.4 %) versus
      the NGT group (2/34, 5.9 %), P = 1.000. CONCLUSIONS: Despite procedural
      differences, FMT via colonoscopy or NGT appears to be highly effective and safe
      for the management of recurrent CDI.

PMID- 22847630
TI  - Multi-target, neuroprotective and neurorestorative M30 improves cognitive
      impairment and reduces Alzheimer's-like neuropathology and age-related
      alterations in mice.
AB  - Based on a multimodal drug design strategy for age-related neurodegenerative
      diseases, we have synthesized a multifunctional nontoxic, brain-permeable iron
      chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the
      anti-Parkinsonian drug, monoamine oxidase-B inhibitor, rasagiline and the
      antioxidant-iron chelator moiety of the 8-hydroxyquinoline derivative of the iron
      chelator, VK28. In the present short overview, we describe the neuroprotective
      and the neurorestorative activity of M30, acting against multiple brain targets,
      including regulation on amyloid beta, neurogenesis, and activation of hypoxia
      inducible factor signaling pathways. The diverse pharmacological properties and
      several pathological targets of M30 make this drug potential valuable for
      therapeutic strategy of Alzheimer's-like neuropathology and aging.

PMID- 22847632
TI  - Verification of stereospecific dyotropic racemisation of enantiopure D and L-1,2
      dibromo-1,2-diphenylethane in non-polar media.
AB  - The first example of a dyotropic rearrangement of an enantiomerically pure,
      conformationally unconstrained, vicinal dibromide confirms theoretical
      predictions: D and L-1,2-dibromo-1,2-diphenylethane racemise stereospecifically
      in refluxing benzene without crossover to the meso-isomer. An orbital analysis of
      this six-electron pericyclic process is presented.

PMID- 22847631
TI  - A new link to mitochondrial impairment in tauopathies.
AB  - Tauopathies like the "frontotemporal dementia with Parkinsonism linked to
      chromosome 17" (FTDP-17) are characterized by an aberrant accumulation of
      intracellular neurofibrillary tangles composed of hyperphosphorylated tau. For
      FTDP-17, a pathogenic tau mutation P301L was identified. Impaired mitochondrial
      function including disturbed dynamics such as fission and fusion are most likely
      major pathomechanisms of most neurodegenerative diseases. However, very little is
      known if tau itself affects mitochondrial function and dynamics. We addressed
      this question using SY5Y cells stably overexpressing wild-type (wt) and P301L
      mutant tau. P301L overexpression resulted in a substantial complex I deficit
      accompanied by decreased ATP levels and increased susceptibility to oxidative
      stress. This was paralleled by pronounced changes in mitochondrial morphology,
      decreased fusion and fission rates accompanied by reduced expression of several
      fission and fusion factors like OPA-1 or DRP-1. In contrast, overexpression of wt
      tau exhibits protective effects on mitochondrial function and dynamics including
      enhanced complex I activity. Our findings clearly link tau bidirectional to
      mitochondrial function and dynamics, identifying a novel aspect of the
      physiological role of tau and the pathomechanism of tauopathies.

PMID- 22847633
TI  - Laboratory studies of organic peroxy radical chemistry: an overview with emphasis
      on recent issues of atmospheric significance.
AB  - Organic peroxy radicals (often abbreviated RO(2)) play a central role in the
      chemistry of the Earth's lower atmosphere. Formed in the atmospheric oxidation of
      essentially every organic species emitted, their chemistry is part of the radical
      cycles that control the oxidative capacity of the atmosphere and lead to the
      formation of ozone, organic nitrates, organic acids, particulate matter and other
      so-called secondary pollutants. In this review, laboratory studies of this peroxy
      radical chemistry are detailed, as they pertain to the chemistry of the
      atmosphere. First, a brief discussion of methods used to detect the peroxy
      radicals in the laboratory is presented. Then, the basic reaction pathways -
      involving RO(2) unimolecular reactions and bimolecular reactions with atmospheric
      constituents such as NO, NO(2), NO(3), O(3), halogen oxides, HO(2), and other
      RO(2) species - are discussed. For each of these reaction pathways, basic
      reaction rates are presented, along with trends in reactivity with radical
      structure. Focus is placed on recent advances in detection methods and on recent
      advances in our understanding of radical cycling processes, particularly
      pertaining to the complex chemistry associated with the atmospheric oxidation of
      biogenic hydrocarbons.

PMID- 22847634
TI  - Selective and non-selective cyclooxygenase inhibitors delay stress fracture
      healing in the rat ulna.
AB  - Anti-inflammatory drugs are widely used to manage pain associated with stress
      fractures (SFxs), but little is known about their effects on healing of those
      injuries. We hypothesized that selective and non-selective anti-inflammatory
      treatments would retard the healing of SFx in the rat ulna. SFxs were created by
      cyclic loading of the ulna in Wistar rats. Ulnae were harvested 2, 4 or 6 weeks
      following loading. Rats were treated with non-selective NSAID, ibuprofen (30
      mg/kg/day); selective COX-2 inhibition, [5,5-dimethyl-3-3 (3 fluorophenyl)-4-(4
      methylsulfonal) phenyl-2 (5H)-furanone] (DFU) (2.0 mg/kg/day); or the novel c5a
      anatagonist PMX53 (10 mg/kg/day, 4 and 6 weeks only); with appropriate vehicle as
      control. Quantitative histomorphometric measurements of SFx healing were
      undertaken. Treatment with the selective COX-2 inhibitor, DFU, reduced the area
      of resorption along the fracture line at 2 weeks, without affecting bone
      formation at later stages. Treatment with the non-selective, NSAID, ibuprofen
      decreased both bone resorption and bone formation so that there was significantly
      reduced length and area of remodeling and lamellar bone formation within the
      remodeling unit at 6 weeks after fracture. The C5a receptor antagonist PMX53 had
      no effect on SFx healing at 4 or 6 weeks after loading, suggesting that PMX53
      would not delay SFx healing. Both selective COX-2 inhibitors and non-selective
      NSAIDs have the potential to compromise SFx healing, and should be used with
      caution when SFx is diagnosed or suspected.

PMID- 22847635
TI  - New views and new tools for complex diseases.

PMID- 22847636
TI  - Membranomyces species are common ectomycorrhizal symbionts in Northern Hemisphere
      forests.
AB  - Membranomyces (Clavulinaceae, Cantharellales) Julich consists of two described
      species of resupinate (crust-like) basidiomycetes. Previous studies indicated
      that Membranomyces falls within the Clavulinaceae, but the phylogenetic position
      of the genus has not been fully resolved. Membranomyces species were thought to
      be saprotrophic until 2003 when Tedersoo et al. detected Membranomyces
      delectabilis on ectomycorrhizal roots of Populus and Picea. Membranomyces was
      previously known only from collections made in eastern Canada and Europe. We
      recently sequenced the ITS rDNA barcode region from Scandinavian herbarium
      specimens identified as M. delectabilis and Membranomyces spurius. Phylogenetic
      analyses of these sporocarp sequences and similar environmental sequences
      indicated that Membranomyces is more diverse than previously thought and forms
      ectomycorrhizas with hosts from a diverse range of plant families in many north
      temperate ecosystems.

PMID- 22847637
TI  - Computational prediction of monosaccharide binding free energies to lectins with
      linear interaction energy models.
AB  - The linear interaction energy (LIE) method to compute binding free energies is
      applied to lectin-monosaccharide complexes. Here, we calculate the binding free
      energies of monosaccharides to the Ralstonia solanacearum lectin (RSL) and the
      Pseudomonas aeruginosa lectin-II (PA-IIL). The standard LIE model performs very
      well for RSL, whereas the PA-IIL system, where ligand binding involves two
      calcium ions, presents a major challenge. To overcome this, we explore a new
      variant of the LIE model, where ligand-metal ion interactions are scaled
      separately. This model also predicts the saccharide binding preference of PA-IIL
      on mutation of the receptor, which may be useful for protein engineering of
      lectins.

PMID- 22847638
TI  - Cardiac computed tomography angiography with automatic tube potential selection:
      effects on radiation dose and image quality.
AB  - PURPOSE: Automatic exposure control (AEC) algorithms are widely available in
      coronary computed tomography angiography (CTA) and have been shown to reduce
      radiation doses by adjusting tube current to patient size. However, the effects
      of anthropometry-based automatic potential selection (APS) on image quality and
      radiation dose are unknown. We sought to investigate the effect of an APS
      algorithm on coronary CTA radiation dose and image quality. MATERIALS AND
      METHODS: For this retrospective case-control study we selected 38 patients who
      had undergone coronary CTA for coronary artery assessment in whom tube potential
      and tube current were selected automatically by a combined automatic tube
      potential and tube current selection algorithm (APS-AEC) and compared them with
      38 controls for whom tube voltage was selected according to standard body mass
      index (BMI) cutoffs and tube current was selected using automatic exposure
      control (BMI-AEC). Controls were matched for BMI, heart rate, heart rhythm, sex,
      acquisition mode, and indication for cardiac CTA. Image quality was assessed as
      contrast-to-noise ratio and signal-to-noise ratio in the proximal coronary
      arteries. Subjective reader assessment was also made. Total radiation dose
      (volume-weighted computed tomography dose index) was measured and compared
      between the 2 groups. In the study group, comparison was made with conventional
      BMI-guided prior protocols (site protocols and Society of Cardiovascular Computed
      Tomography recommendations) through disagreement analysis. RESULTS: The APS-AEC
      cases received 29.8% lower overall radiation dose compared with controls (P=not
      significant). APS-AEC resulted in a significantly higher signal-to-noise ratio of
      the proximal coronary arteries (P<0.01) and contrast-to-noise ratio of the left
      main (P=0.01). In the study cases, the APS resulted in a change in tube potential
      versus site protocols and Society of Cardiovascular Computed Tomography
      recommendations in 45% (n=17) and 50% (n=19) of patients, respectively.
      CONCLUSION: Automated tube potential selection software resulted in significantly
      improved objective image quality versus standard BMI-based methods of tube
      potential selection, without increased radiation doses.

PMID- 22847639
TI  - Interstitial Pneumonia associated with ulcerative colitis: high-resolution
      computed tomography and pathologic findings.
AB  - Pulmonary parenchymal manifestations associated with ulcerative colitis (UC)
      include various conditions such as opportunistic infections, interstitial
      pneumonia, organizing pneumonia, and adverse drug reactions. We present a case of
      interstitial pneumonia associated with UC in a 61-year-old nonsmoking woman. High
      resolution computed tomography demonstrated multifocal ill-defined areas of
      consolidation and ground-glass attenuation with or without traction
      bronchiectasis, predominantly in peripheral lung parenchyma. Lung biopsy showed
      that the closest pathologic pattern in the areas of abnormality was cellular and
      fibrotic nonspecific interstitial pneumonia. We also discuss the evaluation and
      treatment of pulmonary disease possibly related to UC in the clinical course of
      this patient.

PMID- 22847640
TI  - Self-reported prior lung diseases as risk factors for non-small cell lung cancer
      in Mexican Americans.
AB  - This study was conducted to assess the association between prior history of
      respiratory disease and lung cancer among Mexican Americans using data from a
      multi-racial/ethnic lung cancer case-control study. Cases (n = 204) were patients
      with previously untreated lung cancer. Healthy control participants (n = 325)
      were recruited from a large physician group practice. Demographics, cigarette
      use, and history of respiratory disease were collected. Multivariable logistic
      regression models were used to estimate relative risk. Prior history of COPD (OR
      = 2.0; 95 % CI 1.2-3.3) and pneumonia (OR = 2.2; 95 % CI 1.3-3.6) were associated
      with an increased risk of lung cancer. These findings illustrate that prior COPD
      and pneumonia are associated with an increased risk of lung cancer among Mexican
      Americans. To our knowledge, this is one of largest case-control analyses
      assessing the role of respiratory disease and lung cancer risk specifically among
      Mexican-Americans.

PMID- 22847641
TI  - Effects of alanyl-glutamine dipeptide on the expression of colon-inflammatory
      mediators during the recovery phase of colitis induced by dextran sulfate sodium.
AB  - PURPOSE: Glutamine (Gln) is a nutrient with immunomodulatory effects in metabolic
      stressed conditions. This study investigated the effects of Gln on colonic
      inflammatory-mediator expression and mucosal repair in mice with dextran sulfate
      sodium (DSS)-induced colitis. METHODS: C57BL/6 mice received distilled water
      containing 3 % DSS for 5 d to induce colitis. One of the DSS-treated groups was
      intraperitoneally injected with an alanyl (Ala)-Gln solution 3 days before (G
      DSS) while the other group was administered Ala-Gln 3 days after colitis (DSS-G)
      was induced. The Ala-Gln solution provided 0.5 g Gln/kg/d. The saline-DSS group
      (S-DSS) received an identical amount of saline before and after colitis was
      induced to serve as a positive control. RESULTS: The S-DSS group had a shorter
      colon length, higher plasma haptoglobin level, and more-severe colon
      inflammation. Also, the toll-like receptor (TLR)4 level, nuclear factor (NF)
      kappaB activation, and inflammatory cytokine gene expression in the colon were
      higher than those of the normal control group. Gln administration either before
      or after colitis suppressed TLR4 protein levels, decreased plasma haptoglobin,
      and reduced colon inflammation. Histological inflammatory scores were also
      lowered. Compared to the post-colitis Gln group, preventive use of Gln had higher
      colon length, expressions of mucin 2, trefoil factor 3, and heat shock protein 72
      genes were also upregulated in the colon. CONCLUSIONS: These results suggest that
      Gln administered either before or after the colitis mitigated inflammation of
      colitis that was not observed in group without Gln injection. Prophylactic
      treatment with Gln had more-beneficial effects on reducing inflammatory markers
      and enhancing the recovery of mucosa in DSS-induced colitis.

PMID- 22847642
TI  - Differential effects of high-fat-diet rich in lard oil or soybean oil on
      osteopontin expression and inflammation of adipose tissue in diet-induced obese
      rats.
AB  - PURPOSE: To examine the effect of different dietary fat types on osteopontin
      (OPN) expressions and inflammation of adipose tissues in diet-induced obese rats.
      METHODS: Male Sprague-Dawley rats were randomly assigned to one control group fed
      standard diet (LF, n = 10) and two high-fat diet groups fed isoenergy diet rich
      in lard or soybean oil (HL or HS, n = 45 each). Diet-induced obese rats in HL and
      HS group were then subdivided into two groups either continuously fed high-fat
      diet or switched to low-fat diet for 8 more weeks. Fasting serum glucose,
      insulin, and OPN concentrations were assayed and QUICKI was calculated; the
      expression of OPN, IL-6, IL-10, TNF-alpha, NF-kappaB, and F4/80 in adipose tissue
      was determined. RESULTS: Both high-fat diets lead to comparable development of
      obesity characterized by insulin resistance and adipose tissue inflammation.
      Obese rats continuously fed high-fat diet rich in lard oil exhibited the highest
      fasting serum insulin level and adipose tissue OPN, F4/80, TNF-alpha, and NF
      kappaB expression level. In both high-fat diet groups, switching to low-fat diet
      resulted in less intra-abdominal fat mass, decreased expression of F4/80, TNF
      alpha, and NF-kappaB, while decreased OPN expression was only observed in lard
      oil fed rats after switching to low-fat diet. CONCLUSIONS: Reducing diet fat or
      replacing lard oil with soybean oil in high-fat diet alleviates obesity-related
      inflammation and insulin resistance by attenuating the upregulation of OPN and
      macrophage infiltration into adipose tissue induced by high-fat diet.

PMID- 22847643
TI  - Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide
      induced inflammation via inhibition of nuclear factor-kappaB activation in rats.
AB  - PURPOSE: The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B
      (NF-kappaB) activation in the liver, yet the mechanism remains unclear. We
      investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF
      kappaB signaling in the liver of rats fed a GGOH-supplemented diet. METHODS: Rats
      were fed a diet supplemented with or without GGOH for 10 days. Rats were then
      intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and
      fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and the liver damage
      indicators alanine and aspartate aminotransferases (ALT and AST) were assessed.
      Liver mRNA and proteins were assayed for changes in NF-kappaB target genes and
      signal transduction genes. RESULTS: Rats fed a high-dose, GGOH-supplemented diet
      showed significantly lower levels of plasma inflammatory cytokines and ALT and
      AST activities. In the liver, GGOH significantly suppressed NF-kappaB activation
      and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH
      supplementation substantially suppressed mRNA expression of signal transducer
      genes upstream of the IkappaB kinase complex. Western blotting of liver extracts
      further demonstrated the substantial decrease in total IL-1 receptor-associated
      kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower
      signal transduction and inhibition of NF-kappaB after LPS. CONCLUSION: A 10-day,
      high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced
      inflammation and activation of NF-kappaB in rat livers. GGOH significantly
      modulated NF-kappaB signaling molecules, inhibiting its signal transduction and
      activation in the liver, thus protecting against liver damage.

PMID- 22847644
TI  - Praomys tullbergi (Muridae, Rodentia) genome architecture decoded by comparative
      chromosome painting with Mus and Rattus.
AB  - The order Rodentia and in particular the Muridae are characterised by extremely
      high rates of chromosome evolution and remarkable chromosome diversity. The
      Praomys group (Murinae, Muridae and Rodentia) constitutes a diverse and abundant
      group divided into two complexes, the jacksoni complex and the tullbergi complex
      which includes the species Praomys tullbergi. Comparative chromosome painting
      using the two index genomes, Mus musculus and Rattus norvegicus, was performed
      resulting in a high resolution chromosome map for P. tullbergi. The combined use
      of rat and mouse probes and the assistance of the assembly of all the available
      sequencing data from Ensembl genome browser allowed a great dissection of P.
      tullbergi genome, the detection of inversion events and ultimately the refinement
      of P. tullbergi comparative map. A key achievement was the reconstruction of a
      high precision Muroidea ancestral karyotype (Muridae/Cricetidae and Murine) based
      in a broad species analysis combining previous reported comparative maps together
      with the presented data. This permitted the reconstruction of the evolutionary
      history of chromosome changes since the ancestral Muroidea genome and enlightened
      the phylogenetic relationships with the related species mouse and rat. The
      analysis of constitutive heterochromatin and its co-localisation with the
      identified evolutionary breakpoints regions was performed suggesting the
      involvement of repetitive sequences in the chromosome rearrangements that
      originated the present P. tullbergi genome architecture.

PMID- 22847645
TI  - Predicting nucleosome binding motif set and analyzing their distributions around
      functional sites of human genes.
AB  - Nucleosome positioning and remodeling correlate closely with the DNA sequence
      bias. It is possible that DNA motifs, interacted preferentially with histone
      octamers, direct the nucleosome positioning. Exploring the complete set of
      nucleosome binding motifs is of crucial importance for our understanding of the
      roles of nucleosomes in gene regulation. Based on the 8-mer multimodal spectra of
      the human genome, a systematic nucleosome binding motif set is inferred. Its
      structural features and density distributions for different types of sequences
      are consistent with the published data. Distributions of these motifs around
      several functional sites could describe the ground state of nucleosome
      distribution of these regions. Our results strongly support that the predicted
      nucleosome binding motif set is reliable. Our findings indicate that the
      recognition of distinct functional sites or sequences could be greatly improved
      by the help of a nucleosome array.

PMID- 22847646
TI  - On-chip endothelial inflammatory phenotyping.
AB  - Atherogenesis is potentiated by metabolic abnormalities that contribute to a
      heightened state of systemic inflammation resulting in endothelial dysfunction.
      However, early functional changes in endothelium that signify an individual's
      level of risk are not directly assessed clinically to help guide therapeutic
      strategy. Moreover, the regulation of inflammation by local hemodynamics
      contributes to the non-random spatial distribution of atherosclerosis, but the
      mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based
      approach to quantitatively assay metabolic perturbation of inflammatory events in
      human endothelial cells (EC) and monocytes under precise flow conditions.
      Standard methods of soft lithography are used to microfabricate vascular mimetic
      microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers.
      These devices have the advantage of using small volumes of reagents while
      providing a platform for directly imaging the inflammatory events at the membrane
      of EC exposed to a well-defined shear field. We have successfully applied these
      devices to investigate cytokine-, lipid- and RAGE-induced inflammation in human
      aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell
      (THP-1) rolling and arrest on HAEC monolayers that are conditioned under
      differential shear characteristics and activated by the inflammatory cytokine TNF
      alpha. Studies such as these are providing mechanistic insight into
      atherosusceptibility under metabolic risk factors.

PMID- 22847648
TI  - Neurocognitive and mood effects of alcohol in a naturalistic setting.
AB  - OBJECTIVE: The current pilot study aimed to assess the effects of drinking
      alcohol in a naturalistic setting on aspects of performance. METHODS: Thirty
      individuals were approached and tested individually in a university campus bar.
      They provided details regarding alcoholic drinks consumption. Each was
      breathalysed before and after completion of a computerised test battery
      administered on a handheld device. The battery consisted of visual analogue mood
      scales, a series of alcohol-sensitive psychomotor and cognitive tests. RESULTS:
      There were highly significant correlations between measured blood alcohol
      concentrations, estimated units of alcohol consumed and scores on a 'sober-drunk'
      VAS (p < 0.001 in all cases). For performance, there was a characteristic alcohol
      associated shift in the speed/accuracy trade-off (SATO), which was reflected as
      significantly more errors with less effect on speed across several measures
      (including maze performance and Serial Sevens). Individuals who were more
      intoxicated were also significantly less alert. CONCLUSIONS: The data suggest
      that controlled laboratory tests into the effects of alcohol intoxication may
      have ecological validity, with SATO shifts amongst the characteristic impairments
      seen in both controlled and naturalistic settings.

PMID- 22847649
TI  - Phylogenetic separation in limb use in captive gibbons (Hylobatidae): a
      comparison across the primate order.
AB  - Although there have been few studies of self-scratching in primates, some have
      reported distinct differences in whether hands or feet are used, and these
      variations seem to reflect the evolutionary history of the Order. Monkeys and
      prosimians use both hands and feet to self-scratch while African great apes use
      hands almost exclusively. Gibbons represent an evolutionary divergence between
      monkeys and great apes and incidental observations at the Gibbon Conservation
      Center pointed to a difference in self-scratching among the four extant gibbon
      genera (Hoolock, Nomascus, Symphalangus, and Hylobates). To validate and further
      explore these preliminary observations, we collected systematic data on self
      scratching from 32 gibbons, including nine species and all four genera. To
      supplement gibbon data, we also collected self-scratching information from 18
      great apes (four species), five prosimians (two species), 26 New World Monkeys
      (nine species) and 20 Old World Monkeys (seven species). All monkeys and some
      prosimians used both hands and feet to self-scratch, whereas one prosimian
      species used only feet. All African great apes used hands exclusively (orangutans
      were an exception displaying occasional foot-use). This appears to represent a
      fundamental difference between monkeys and great apes in limb use. Interestingly,
      there was a clear difference in self-scratching between the four gibbon genera.
      Hylobates and Symphalangus self-scratched only with hands (like all African great
      apes), while Hoolock and Nomascus self-scratched with both hands and feet (like
      monkeys and prosimians). This difference in gibbon behavior may reflect the
      evolutionary history of gibbons as Hoolock and Nomascus are thought to have
      evolved before both Hylobates and Symphalangus. What evolutionary pressures led
      to this divergent pattern is currently opaque; however, this shift in limb
      preference may result from niche separation across the order facilitating
      differences in the behavioral repertoire associated with hind and forelimbs.

PMID- 22847650
TI  - Lack of aneurysm formation after carotid artery ligation in rabbits: a polymer
      MICROFIL(r) study.
AB  - INTRODUCTION: Previous studies have noted formation of saccular aneurysms along
      the distal basilar artery/P1 segments after carotid ligation in rabbits. In this
      prospective study we employed MICROFIL(r), a polymer, which was used to fill the
      entire arterial tree, to examine the incidence of microaneurysm formation
      following right common carotid artery (RCCA) ligation in rabbits. METHODS: RCCA
      ligation was performed in 18 New Zealand White rabbits for 0 day (n = 2), 3 weeks
      (n = 6), or 16 weeks (n = 10). Three control rabbits without carotid surgery were
      sacrificed at 4 weeks. At the time of sacrifice, MICROFIL(r) MV-122 yellow was
      injected through left CCA to fill cerebral vasculature. After gross photographs
      were taken, specimens were embedded, sectioned, and stained for histopathological
      evaluation. Tissue and sections were carefully evaluated for microaneurysm
      formation, defined as a localized dilatation of the vessel wall, associated with
      fragmentation or complete loss of the internal elastic lamina (IEL), and/or
      medial degeneration. RESULTS: Gross examination with MICROFIL(r) opacification
      demonstrated no evidence of saccular aneurysm formation, but prominent
      perforating vessels were present in all 19 cases at, or adjacent to, the basilar
      terminus. Branches noted upon gross examination corresponded histologically to
      small, saccular contour defects, which demonstrated apparent loss of the IEL and
      apparent medial thinning. These observations, however, were a consequence of
      sectioning through the bases of perforating arteries, which simulated
      microaneurysm formation. CONCLUSIONS: Unilateral carotid ligation does not induce
      microaneurysm formation at the basilar terminus in rabbits. Prominent perforating
      arteries as well as tissue injury from the processing may simulate "aneurysms"
      histologically.

PMID- 22847652
TI  - Determinants of in-hospital death after acute spinal cord injury: a population
      based study.
AB  - OBJECTIVES: First, to evaluate the influence of comorbid diseases and concomitant
      injuries on the risk of in-hospital death after traumatic spinal cord injury
      (TSCI). Second, to identify the risk characteristics of TSCI patients with
      likelihood of death. STUDY DESIGN: Population-based retrospective cohort study.
      SETTING: Sixty-two acute care hospitals in South Carolina, USA. METHODS: Records
      of 3389 TSCI patients hospitalized with acute TSCI were evaluated. Days elapsing
      from the date of injury to date of death established the survival time (T). Cox
      regression examined risk of in-hospital death as a function of counts of comorbid
      conditions and injuries along with their joint effects controlling for other
      covariates. RESULTS: Counts of comorbid conditions and injuries showed dose
      dependent risk of death while in-hospital independent of demographical and
      clinical covariates. Hazard ratios (HR) for counts 3+, 2 and 1 comorbid
      conditions were 2.19 (P<0.001), 1.73 (P=0.005) and 1.20 (P=0.322), respectively.
      For counts of 4+, 3 and 2 other injuries were 1.85 (P<0.001), 1.81 (P<0.001) and
      1.46 (P=0.022), respectively. The joint effect of the two was transadditive with
      statistically significant HR ranging from 1.72-3.14. CONCLUSION: Counts of
      comorbid conditions and injured body regions strongly indicate risk of in
      hospital death after TSCI and their joint effects elicited dose-dependent
      gradient independent of demographical and clinical covariates. Assessing risk of
      in-hospital death based on joint use of counts of comorbid diseases and injuries
      is highly informative to target TSCI patients at high risk of dying.

PMID- 22847653
TI  - Acromioclavicular joint arthrosis in persons with spinal cord injury and able
      bodied persons.
AB  - OBJECTIVE: To compare the prevalence, severity and risk of acromioclavicular (AC)
      joint arthrosis in persons presenting with shoulder pain between a spinal cord
      injury (SCI) and able-bodied population. In the SCI population, prevalence and
      severity of AC joint arthrosis were examined with respect to age, gender and
      lesion characteristics. METHODS: Retrospective analysis of medical records and
      magnetic resonance images (MRI) collected in an outpatient orthopaedics clinic.
      RESULTS: Sixty-eight persons with SCI and 105 able-bodied persons were included
      in the study. The overall MRI prevalence of AC joint arthrosis was 98% and 92%,
      respectively. In both groups AC joint arthrosis was frequently accompanied by MRI
      diagnosis of rotator cuff tears and biceps tendon ruptures. Sensitivity of
      clinical testing was found to be low in SCI (0.31) and in able-bodied persons
      (0.24). The odds of increasingly severe arthrosis were nearly four times higher
      in persons with SCI as compared with able-bodied persons (P<0.0001), about 72%
      lower in females as compared with males (P=0.0001), and 10% higher per additional
      year of age (P<0.0001). Arthrosis severity in the SCI-group was weakly associated
      with time since injury, not with neurological classification of SCI or level of
      injury (paraplegia vs tetraplegia). CONCLUSION: SCI patients presenting with
      shoulder pain showed similar prevalence, yet more advanced, AC joint arthrosis
      than able-bodied patients. As early diagnosis of arthrosis is a prerequisite for
      the initiation of successful conservative interventions of shoulder
      deterioration, we recommend routine assessment of shoulder status including
      diagnostic imaging during check-ups.

PMID- 22847654
TI  - Impact of benchmarking and clinical decision making tools on rehabilitation
      length of stay following spinal cord injury.
AB  - STUDY DESIGN: Performance improvement initiative. OBJECTIVES: To improve
      efficiency of spinal cord rehabilitation by reducing length of stay (LOS) while
      maintaining or improving patient outcomes. SETTING: Academic hospital in Canada.
      METHODS: LOS benchmarking was completed using national comparator data from the
      Canadian Institute for Health Information (CIHI). Clinical decision-making tools
      were developed to support implementation and sustainability. A standardized
      'tentative discharge date' calculator was created to establish objective LOS
      targets. Defined discharge criteria and an accompanying clinical decision tree
      were developed to support team decision making and improve transparency. A
      revised patient census tool was also implemented to improve team communication
      and facilitate data collection. The initiative was implemented in March 2010 and
      the following metrics were evaluated: LOS, Functional Independence Measure (FIM)
      change and FIM efficiency. RESULTS: Outcomes are reported for the 2010/11 fiscal
      year, and compared with the two prior fiscal years. Mean LOS for individuals
      undergoing initial inpatient rehabilitation was 71.5 days for 2010/11, a 14 and
      17% reduction compared with the 2008/09 and 2009/10 fiscal years, respectively.
      While LOS decreased, FIM change increased 9 and 16% compared with 2008/09 and
      2009/10, respectively. Similarly, FIM efficiency increased 54 and 32% compared
      with 2008/09 and 2009/10. CONCLUSION: The use of benchmarking and decision
      support tools improved rehabilitation efficiency while increasing standardization
      in practice and transparency in LOS determination.

PMID- 22847651
TI  - All about running: synaptic plasticity, growth factors and adult hippocampal
      neurogenesis.
AB  - Accumulating evidence from animal and human research shows exercise benefits
      learning and memory, which may reduce the risk of neurodegenerative diseases, and
      could delay age-related cognitive decline. Exercise-induced improvements in
      learning and memory are correlated with enhanced adult hippocampal neurogenesis
      and increased activity-dependent synaptic plasticity. In this present chapter we
      will highlight the effects of physical activity on cognition in rodents, as well
      as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density,
      neurotransmission and growth factors, in particular brain-derived nerve growth
      factor (BDNF).

PMID- 22847655
TI  - Towards beta-selectivity in functional estrogen receptor antagonists.
AB  - Based on the benzo[b]naphtho[1,2-d]furan and benzo[b]naphtho[1,2-d]thiophene
      frameworks, a series of ligands with different basic side chains (BSCs) has been
      synthesized and pharmacologically evaluated. Also, their binding modes have been
      modelled using docking techniques. It was found that the introduction of a BSC in
      these systems brings about a decrease of affinity for both estrogen receptors
      alpha and beta in an in vitro competitive binding assay. However, two full
      antagonists of the estrogen receptor beta (9c and 9f) have been discovered, with
      potency in the low micromolar concentration in a cell-based luciferase reporter
      assay, and completely devoid of activity against the alpha receptor at the same
      concentration range. Differences in the ERalpha/ERbeta binding modes have also
      been rationalized with the help of molecular modelling techniques. This
      interesting functional profile could be used to elucidate the physiological role
      of each ER subtype.

PMID- 22847656
TI  - Factors affecting spatial variation of polycyclic aromatic hydrocarbons in
      surface soils in North China Plain.
AB  - The spatial variation in concentrations of 16 polycyclic aromatic hydrocarbons
      (PAHs) in surface soils in the North China Plain and the influential factors were
      examined in the present study. High concentrations of the sum of 16 PAHs
      (?PAH(16) ) appeared in cities and their surrounding areas. Emissions and soil
      organic carbon (SOC) content significantly regulated spatial differentiation of
      PAH contamination in soils in the study area. Compared with emissions,
      concentrations of individual and total PAHs in soils were more closely controlled
      by the SOC content. Furthermore, concentrations of PAH species with lower
      molecular weight (e.g., two- or three-ring) in surface soils were more strongly
      correlated with the SOC content in comparison with those of higher molecular
      weight (e.g., five- or six-ring), mainly because of their higher saturated vapor
      pressure, thus higher mobility. The spatial variation of PAH species in soils in
      the North China Plain tended to be larger with increasing benzene ring numbers,
      and the difference in physicochemical properties of PAH species determined their
      distinct spatial distribution characteristics. The present study highlights the
      relative importance of emissions and SOC content in spatial variation of PAHs and
      the dependence of the spatial distribution characteristics of PAH species in
      surface soils on their physicochemical properties at a regional scale. Results of
      the present work are helpful for regional risk assessment of the contaminants
      tested.

PMID- 22847657
TI  - Adaptive shoot and root responses collectively enhance growth at optimum
      temperature and limited phosphorus supply of three herbaceous legume species.
AB  - BACKGROUND AND AIMS: Studies on the effects of sub- and/or supraoptimal
      temperatures on growth and phosphorus (P) nutrition of perennial herbaceous
      species at growth-limiting P availability are few, and the impacts of temperature
      on rhizosphere carboxylate dynamics are not known for any species. METHODS: The
      effect of three day/night temperature regimes (low, 20/13  degrees C; medium,
      27/20  degrees C; and high, 32/25  degrees C) on growth and P nutrition of Cullen
      cinereum, Kennedia nigricans and Lotus australis was determined. KEY RESULTS: The
      highest temperature was optimal for growth of C. cinereum, while the lowest
      temperature was optimal for K. nigricans and L. australis. At optimum
      temperatures, the relative growth rate (RGR), root length, root length per leaf
      area, total P content, P productivity and water-use efficiency were higher for
      all species, and rhizosphere carboxylate content was higher for K. nigricans and
      L. australis. Cullen cinereum, with a slower RGR, had long (higher root length
      per leaf area) and thin roots to enhance P uptake by exploring a greater volume
      of soil at its optimum temperature, while K. nigricans and L. australis, with
      faster RGRs, had only long roots (higher root length per leaf area) as a
      morphological adaptation, but had a higher content of carboxylates in their
      rhizospheres at the optimum temperature. Irrespective of the species, the amount
      of P taken up by a plant was mainly determined by root length, rather than by P
      uptake rate per unit root surface area. Phosphorus productivity was correlated
      with RGR and plant biomass. CONCLUSIONS: All three species exhibited adaptive
      shoot and root traits to enhance growth at their optimum temperatures at growth
      limiting P supply. The species with a slower RGR (i.e. C. cinereum) showed only
      morphological root adaptations, while K. nigricans and L. australis, with faster
      RGRs, had both morphological and physiological (i.e. root carboxylate dynamics)
      root adaptations.

PMID- 22847658
TI  - Pain in children: knowledge and perceptions of the nursing staff at a rural
      tertiary care teaching hospital in India.
AB  - OBJECTIVES: To assess the knowledge and perception regarding pain amongst nursing
      staff and to determine whether varying clinical exposure to painful procedures in
      children had any association with their perception of pain. METHODS: A
      consensually validated questionnaire containing combination of questions from
      basic (must know) and advanced (nice to know) areas of knowledge about nursing
      pediatric patients and questions related to nurses' perception about pain in
      pediatric patients was administered to the eligible nursing staff at a Rural
      Tertiary Care Hospital in Western India. The responses to the questionnaire were
      analyzed using descriptive statistics and the comparisons were made by applying
      chi-square test. RESULTS: Three Hundred and Fifty one usable questionnaires
      (83.37 %) out of 421 were returned. The knowledge of the nurses in general
      regarding pain was observed to be poor. Only 60 % of all the nurses had complete
      knowledge of all the basic questions asked. Only 3.1 % had answered all of the
      five advanced questions correctly, while 96.9 % of the nurses had answered one or
      more questions incorrectly. CONCLUSIONS: The deficit in knowledge and
      shortcomings in perception of nursing staff needs to be addressed and steps need
      to be taken to improve the nurse's knowledge and modify beliefs and attitude of
      the nursing staff towards the pain of the pediatric patients.

PMID- 22847659
TI  - The first ionothermal synthesis of a germanium phosphate with one-dimensional
      chain-like structure.
AB  - A novel germanium phosphate with a chain-like framework constructed from
      GeO(4)N(2) octahedra and PO(4) tetrahedra,
      [NH(4)](2)[Ge(NH(3))(2)(PO(4))(2)].0.38H(2)O, was first synthesized via in situ
      decomposition of urea from ionic eutectic mixtures comprising urea and quaternary
      ammonium salts.

PMID- 22847672
TI  - SENSE with improved tolerance to inaccuracies in coil sensitivity maps.
AB  - In this work, an extension of the Cartesian sensitivity encoding (SENSE) parallel
      imaging framework is proposed. In the well-known SENSE solution, the
      overdetermined reconstruction inversion problem is optimized to get the highest
      signal-to-noise ratio in the image. In this extension, the probability of
      artifacts due to incorrect knowledge of the receiver coil sensitivities is also
      taken into account. This is realized by assuming an uncertainty in measured
      receiver coil sensitivities to enable weighting of residual artifact level and
      signal-to-noise ratio in the inversion problem. This inversion problem can still
      be solved by a least-squares optimization without the need of any complex
      iterative scheme. Results in abdominal imaging show that artifact levels can be
      substantially reduced, at the cost of a signal-to-noise ratio penalty. The size
      of the signal-to-noise ratio penalty depends on the assumed inaccuracy of the
      coil sensitivities, sensitivity encoding acceleration factor, and coil
      configuration.

PMID- 22847673
TI  - GPU-accelerated computation of electron transfer.
AB  - Electron transfer is a fundamental process that can be studied with the help of
      computer simulation. The underlying quantum mechanical description renders the
      problem a computationally intensive application. In this study, we probe the
      graphics processing unit (GPU) for suitability to this type of problem. Time
      critical components are identified via profiling of an existing implementation
      and several different variants are tested involving the GPU at increasing levels
      of abstraction. A publicly available library supporting basic linear algebra
      operations on the GPU turns out to accelerate the computation approximately 50
      fold with minor dependence on actual problem size. The performance gain does not
      compromise numerical accuracy and is of significant value for practical purposes.

PMID- 22847671
TI  - Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross-talk in the bone
      marrow of multiple myeloma patients.
AB  - Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high
      affinity and selectivity to fibroblast growth factor-2 (FGF2), thus inhibiting
      its pro-angiogenic activity. Here we investigated the effects of PTX3 on
      monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma
      (MM) patient-derived bone marrow (BM) plasma cells (PCs), endothelial cells
      (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross
      talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was
      evaluated by ELISA. Functional studies, including cell viability, wound healing,
      chemotaxis, and Matrigel((r)) assays, were performed on MGUS and MM ECs and FBs
      upon the PTX3 treatment. Through western blot PTX3-induced modulation in FGF2/FGF
      receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through
      western blot. Co-cultures between MM ECs/FBs and human PC lines were used to
      evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were
      studied by flow cytometry. PTX3 provides a direct time- and dose-dependent
      apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC
      lines. PTX3 inhibits migration of MM ECs and FBs in a dose-dependent manner, and
      impacts in vitro and in vivo FGF2-mediated MM angiogenesis. Co-cultures of PCs
      and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and
      adhesion. We conclude that PTX3 is an anti-angiogenic factor in MM and behaves as
      a cytotoxic molecule on MM cells by inhibiting the cross-talk between PCs and
      ECs/FBs.

PMID- 22847674
TI  - [Recommendations of the Working Group of Arrhythmias of the German Society of
      Cardiology on the approach to patients with Riata(r) and Riata ST(r) leads (St.
      Jude Medical). Nucleus of the Working Group of Arrhythmias of the German Society
      of Cardiology].
AB  - Riata(r) and Riata ST(r) implantable cardioverter defibrillator (ICD) leads (St.
      Jude Medical, Sylmar, CA) show an increased incidence of insulation defects,
      particularly "inside-out" lead fracture where inner, separately insulated cables
      penetrate through the surrounding silicone of the lead body. The exact incidence
      of Riata(r) lead problems is not clear and seems to range between 2-4% per year
      in the first 5 years after implantation according to new registry data. We
      recommend beyond a detailed information the following care of patients with
      Riata(r) and Riata ST(r) leads: 1) Activation of automatic ICD alerts, 2) remote
      monitoring with automatic daily alerts whenever possible, 3) monthly ICD controls
      in patients at high risk (pacemaker dependency, history of ventricular
      tachyarrhythmias) and high or moderate lead-related risk (8F, 7F single coil), 3
      monthly controls in moderate patient and lead-related risk, 3 to 6-monthly
      controls in low patient and lead-related risk (no bradycardia, no history of
      ventricular tachyarrhythmia). Every ICD control should include meticulous
      analysis of oversensing artifacts in stored electrograms (EGMs) of sustained and
      non-sustained ventricular tachyarrhythmias and registration of EGMs during
      provocation testing (pectoral muscle activity, arm movements). If electrical
      abnormalities are observed, reoperation with addition of a new ICD lead is
      recommended; lead extraction only if indicated according to current guidelines.
      Fluoroscopy should only be performed if electrical abnormalities are found by an
      experienced electrophysiologist and a high frame rate and resolution. Management
      of fluoroscopic abnormalities in the absence of electrical abnormalities is not
      clear. Therefore, routine fluoroscopy of patients with Riata(r) leads without
      electrical abnormalities is not recommended.

PMID- 22847675
TI  - The effects of dietary fatty acid composition in the post-sucking period on
      metabolic alterations in adulthood: can omega3 polyunsaturated fatty acids
      prevent adverse programming outcomes?
AB  - Early life nutrition is important in the regulation of metabolism in adulthood.
      We studied the effects of different fatty acid composition diets on adiposity
      measures, glucose tolerance, and peripheral glucocorticoid (GC) metabolism in
      overfed neonatal rats. Rat litters were adjusted to a litter size of three (small
      litters (SLs)) or ten (normal litters (NLs)) on postnatal day 3 to induce
      overfeeding or normal feeding respectively. After weaning, SL and NL rats were
      fed a omega6 polyunsaturated fatty acid (PUFA) diet (14% calories as fat, soybean
      oil) or high-saturated fatty acid (high-fat; 31% calories as fat, lard) diet
      until postnatal week 16 respectively. SL rats were also divided into the third
      group fed a omega3 PUFA diet (14% calories as fat, fish oil). A high-fat diet
      induced earlier and/or more pronounced weight gain, hyperphagia, glucose
      intolerance, and hyperlipidemia in SL rats compared with NL rats. In addition, a
      high-fat diet increased 11beta-hsd1 (Hsd11b1) mRNA expression and activity in the
      retroperitoneal adipose tissue of both litter groups compared with standard chow
      counterparts, whereas high-fat feeding increased hepatic 11beta-hsd1 mRNA
      expression and activity only in SL rats. SL and a high-fat diet exhibited
      significant interactions in both retroperitoneal adipose tissue and hepatic
      11beta-HSD1 activity. Dietary omega3 PUFA offered protection against glucose
      intolerance and elevated GC exposure in the retroperitoneal adipose tissue and
      liver of SL rats. Taken together, the results suggest that dietary fatty acid
      composition in the post-sucking period may interact with neonatal feeding and
      codetermine metabolic alterations in adulthood.

PMID- 22847676
TI  - Left ventricular noncompaction complicated by mitral valve prolapse: report of a
      case.
AB  - A 31-year-old male was diagnosed with congestive heart failure due to left
      ventricular noncompaction and coarctation of the aorta by echocardiography and
      computed tomography. He also developed mitral valve prolapse of the posteromedial
      commissural leaflet due to rupture of chordae tendineae. Segmental leaflet
      resection was performed with ring annuloplasty. Aorto-bifemoral bypass was
      carried out simultaneously to attenuate the ventricular afterload. His
      postoperative course was uneventful.

PMID- 22847677
TI  - Health-related quality of life in patients with hepatocellular carcinoma: the
      mediation effects of illness perceptions and coping.
AB  - BACKGROUND: The aims of this study were to explore health-related quality of life
      (HRQOL) in patients with hepatocellular carcinoma (HCC). We report the following:
      (1) differences in HRQOL between patients with HCC and the general population;
      (2) significant physical and psychological predictors of HRQOL; and (3) mediation
      effects of illness perceptions and coping on HRQOL. METHODS: Patients with HCC (n
      = 286) from Taiwan completed standardized measures of HRQOL, illness perception
      (cognitive representations, emotional representations and illness
      comprehensibility) and coping (emotion-oriented and problem-orientation coping).
      Demographic and physical variables were also collected. RESULTS: Patients with
      HCC had worse global HRQOL, physical, role, cognitive and social functioning, but
      better emotional functioning than the general population. Physical variables and
      cognitive representation were significant predictors of global HRQOL, physical
      functioning and emotional functioning. Cognitive representation mediated the
      relationships between physical variables and global HRQOL, physical functioning
      and emotional functioning, but coping only mediated the relationship between
      cognitive representation and global HRQOL. CONCLUSIONS: The results suggest that
      physical variables have direct effects on global HRQOL and physical functioning,
      but there were also partial mediations through cognitive representation. The
      effect of physical variables on emotional functioning was mediated through
      cognitive and emotional representations. Patients with better performance status
      and positive illness perceptions tended to report better HRQOL, but those with
      negative illness perceptions and who used more emotion-oriented coping had worse
      HRQOL. Limitations of the work associated with use of theory and measures
      developed in Europe and the US are discussed, as are the clinical implications
      for patients with HCC.

PMID- 22847678
TI  - Increased cardiovascular risk factors in different rheumatic diseases compared
      with the general population.
AB  - OBJECTIVES: To study the prevalence of cardiovascular risk factors among patients
      attending a rheumatology outpatient clinic in comparison with the general
      population. METHODS: Cross-sectional comparison between a rheumatic outpatient
      cohort of consecutive patients (n = 1233) between 36 and 75 years of age
      attending the Arthritis Center Twente (ACT) in the year 2009: RA (n = 546), gout
      (n = 129), OA (n = 168), CTD (n = 85), PMR (n = 91) and chronic localized or
      generalized pain syndromes (CPSs; n = 214) and a random sample from a long
      lasting population-based health study in the Netherlands (n = 4523). The main
      outcome measures were hypertension (systolic blood pressure >= 140 mmHg and/or a
      diastolic blood pressure >= 90 mmHg and/or the use of antihypertensive
      medication), abnormal cholesterol profile (total cholesterol >= 6.5 mmol/l,
      and/or high-density lipoprotein < 0.9 mmol/l and/or use of lipid lowering
      medication), overweight (BMI >= 25 kg/m(2)), obesity (BMI >= 30 kg/m(2)) and
      cigarette smoking habits (self-reported current smoking). RESULTS: Compared with
      the general population, patients with rheumatic diseases have a significantly
      higher prevalence of hypertension (P(ACT) = 68%, P(general) = 57%), being
      overweight (P(ACT) = 72%, P(general) = 62%), obesity (P(ACT) = 30%, P(general) =
      17%) and cigarette smoking (P(ACT) = 26%, P(general) = 21%). The worst risk
      profile was found in gout patients, with higher prevalence of all cardiovascular
      risk factors studied. CONCLUSION: Lifestyle-associated potentially modifiable
      cardiovascular risk factors are over-represented along the whole spectrum of
      chronic rheumatic diseases, and not only in RA, as suggested by preceding
      studies.

PMID- 22847679
TI  - Worst-case future scenarios of patients with rheumatoid arthritis: a cross
      sectional study.
AB  - OBJECTIVE: The time trade-off is a health-related quality of life instrument that
      measures valuations for health states (utilities) by asking patients to value
      their health state anchored on a scale between death (0) and perfect health (1).
      Dying earlier is not perceived as a realistic worst-case consequence of the
      disease by RA patients. Of the previous focus groups study on RA patients, five
      worst-case future scenarios emerged. The aim of this study was to examine which
      potential worst-case scenario was the most appropriate for RA patients to use in
      utility calculation. METHODS: In a cross-sectional study of 74 consecutive RA
      patients visiting the rheumatology outpatient clinic, participants were presented
      with descriptions of the five worst-case future scenarios. In pairwise
      comparisons, patients had to choose the scenario that would be the worst to
      experience. The worst-case future scenario was defined by the scenario that was
      chosen by a significantly greater proportion of participants than could be
      expected based on chance (20%). Therefore, analysis based on a single fraction (
      ) was used and 95% CI was calculated. RESULTS: The scenario being dependent on
      others was chosen most often as the worst to experience [by 35% of participants
      (95% CI 24%, 46%)] and significantly more often than could be expected based on
      chance (  = 0.35, z = 6.45, P = 0.00). CONCLUSION: The scenario being dependent
      on others is likely to be the most appropriate worst-case future scenario for RA
      patients. Using an alternative anchor could improve the validity and
      responsiveness of the time trade-off in RA patients.

PMID- 22847680
TI  - Alterations of skeletal muscle microcirculation detected by blood oxygenation
      level-dependent MRI in a patient with granulomatosis with polyangiitis.

PMID- 22847681
TI  - Increased expression of interleukin-32 in the inflamed ileum of ankylosing
      spondylitis patients.
AB  - OBJECTIVE: To study the mRNA expression and protein tissue distribution of IL-32
      in ileal biopsy specimens from patients with AS. METHODS: Quantitative gene
      expression analysis, by real-time PCR, of IL-32, IL-1beta, IL-10, TNF-alpha and
      IFN-gamma was performed on ileal biopsies of 15 AS and 15 Crohn's disease (CD)
      patients and 10 healthy subjects (HSs). IL-32 tissue distribution was evaluated
      by immunohistochemistry. The effect of IL-32 on the production of IL-10 by
      intestinal epithelial cell lines was also evaluated. RESULTS: In the ileal
      specimens of patients with AS and intestinal chronic inflammation, significant up
      regulation of IL-32 at both the mRNA and protein levels was found as compared
      with non-inflamed AS patients and controls. IL-32 over-expression in AS was
      accompanied by a significant increase of IL-10 but not of cytokines involved in
      IL-32 induction. IL-32 stimulates intestinal epithelial cell lines in vitro to
      produce IL-10. CONCLUSION: Our findings suggest IL-32 as an important cytokine
      probably involved in the innate immune response occurring in early phases of
      intestinal inflammation, where it seems to play a prevalent protective role.

PMID- 22847682
TI  - Head-to-head comparison of quantitative and semi-quantitative ultrasound scoring
      systems for rheumatoid arthritis: reliability, agreement and construct validity.
AB  - OBJECTIVE: To evaluate the reliability and agreement of semi-quantitative scoring
      (SQS) and quantitative scoring (QS) systems. To compare the two types of scoring
      system and investigate the construct validity for both scoring systems. METHODS:
      A total of 46 RA patients (median disease duration of 6.5 years) were enrolled in
      the study. They were investigated with colour Doppler ultrasound using the
      central position of the wrist. Disease activity score based on 28 joints (DAS-28)
      was determined for all patients using CRP. Two participants trained in the SQS
      system and two in the QS system evaluated the 46 anonymized images. All images
      were scored twice by each of the two assessors in order to assess both intra- and
      inter-reader reliability. RESULTS: The reliability for the two systems were 0.964
      for the QS, and 0.817 for the SQS, with a comparable inter-reader agreement for
      both scoring systems; 95% limits of agreement for the QS being between -7.7% and
      +6.7% on the colour fraction scale (0-100%), whereas SQS was between -0.8 and
      +0.8 on the ordinal scale from 0 to 3. There was a direct but non-linear
      relationship between the two modalities (Spearman's r = 0.73) and critical
      conceptual issues in the agreement between the scoring systems were revealed. The
      construct validity was poor for both systems with only a weak correlation to CRP.
      CONCLUSION: High reliability and good agreement of both scoring systems were
      found when applied to the same patient cohort. Different scoring systems appear
      to be highly correlated.

PMID- 22847683
TI  - Knowledge about various contraceptive methods in young women with and without
      eating disorders.
AB  - OBJECTIVE: To determine if young women with eating disorders (EDs) have altered
      views about the risks/benefits of different forms of birth control than the
      general population. METHOD: Data was collected using a cross-sectional, survey
      based study of postmenarchal women aged 13-25 years with a diagnosed ED (n = 50)
      or no history of disordered eating patterns (n =57). RESULTS: Despite having a
      higher level of education (p = 0.04) and no differences in sexual history (p =
      0.16), ED patients were less knowledgeable than controls about the health risks
      and benefits, effectiveness in preventing HIV, and effectiveness in preventing
      pregnancy of various methods of birth control (p<= 0.05). DISCUSSION: ED patients
      may be incorrectly presumed to be asexual while working on recovery; physicians
      may need to take extra time to educate ED patients about their personal risks of
      unintended pregnancy, sexually transmitted infections, and the benefits that
      different methods of contraception can provide.

PMID- 22847684
TI  - High-performance liquid chromatographic enantioseparation of unusual isoxazoline
      fused 2-aminocyclopentanecarboxylic acids on (+)-(18-crown-6)-2,3,11,12
      tetracarboxylic acid-based chiral stationary phases.
AB  - The enantiomers of four unusual isoxazoline-fused 2-aminocyclopentanecarboxylic
      acids were directly separated on chiral stationary phases containing (+)-(18
      crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector. The nature of the
      alcoholic modifier (MeOH, EtOH, IPA) exerted a great effect on the retention,
      whereas the selectivity and resolution did not change substantially. Two types of
      dependence of retention on alcohol content were detected: k(1) increased
      continuously with increasing alcohol content or a U-shaped retention curve was
      observed. A comparison of the chromatographic data obtained with HCOOH, AcOH,
      TFA, HClO(4), H(2)SO(4), or H(3)PO(4) as acidic modifier at a constant
      concentration demonstrated that in most cases, larger k values were obtained on
      the application of AcOH or HCOOH, and an increase of the acid content resulted in
      a decrease of retention. Some mechanistic aspects of the chiral recognition
      process are discussed with respect to the structures of the analytes and
      selector. The sequence of elution of the enantiomers was determined in all cases.

PMID- 22847685
TI  - Photodynamic inactivation of Streptococcus mutans and Streptococcus sanguinis
      biofilms in vitro.
AB  - The purpose of this study was to evaluate specific effects of photodynamic
      inactivation (PDI) using erythrosine (ER) and Rose Bengal (RB) photosensitizers
      and a blue light-emitting diode (LED) on the viability of Streptococcus mutans
      and Streptococcus sanguinis biofilms. Biofilms were grown in acrylic disks
      immersed in broth to production of biofilms, inoculated with microbial suspension
      (10(6) cells/mL) and incubated for 48 h. After the formation of biofilms, the
      effects of the photosensitizers ER and RB at a concentration of 5 MUM for 5 min
      and blue LED (455 +/- 20 nm) for 180 s, photosensitizers alone and conjugated
      were evaluated. Next, the disks were placed in tubes with sterile physiological
      solution (0.9 % sodium chloride) and sonicated for to disperse the biofilms.
      Tenfold serial dilutions were carried and aliquots seeded in brain heart infusion
      agar which were then incubated for 48 h. Then the numbers colony-forming units
      per milliliter (CFU/mL; log10) were counted and analyzed statistically (ANOVA,
      Tukey test, P <= 0.05). Significant decreases in the viability of all
      microorganisms were observed for biofilms exposed to PDI mediated by both
      photosensitizers. The reductions with RB and ER were, 0.62 and 0.52 log10 CFU mL(
      1) for S. mutans biofilms (p=0.001), and 0.95 and 0.88 log10 CFU mL(-1) for S.
      sanguinis biofilms (p=0.001), respectively. The results showed that biofilms
      formed in vitro by S. mutans and S. sanguinis, were sensitive to PDI using a blue
      LED associated with photosensitizers ER or RB, indicating its use in the control
      of caries and periodontal diseases.

PMID- 22847687
TI  - ENSO effects on delta18O, delta2H and d-excess values in precipitation across the
      U.S. using a high-density, long-term network (USNIP).
AB  - RATIONALE: Isotope (delta(18)O and delta(2)H values) ratios in precipitation have
      been central to understanding changes in Earth's climate as recorded in ice,
      coral, speleothems, lake varves and long-lived plants. Understanding how climate
      phases (i.e. ENSO) affect the spatial and temporal patterns of delta(18)O and
      delta(2)H values in precipitation has, however, been uncertain across the USA.
      METHODS: A spatial precipitation isotope network (USNIP) has been established
      that aims to: (1) characterize the delta(18)O, delta(2)H and d-excess values in
      precipitation across the USA with the highest spatially dense network of
      measurements yet undertaken; (2) quantify the annual and seasonal patterns of
      precipitation delta(18)O and delta(2)H values that may be affected by ENSO
      climate phases; and (3) provide a new isotope database for scientific studies
      that can be incorporated into NEON, BASIN, GNIP, and IsoMAP. RESULTS: On average,
      precipitation delta(18)O and delta(2)H values are very low in the northern Rocky
      Mountain region (~ -150/00 delta(18)O, and ~ -1200/00 delta(2)H), and
      precipitation delta(18)O and delta(2)H values are relatively higher along the
      Gulf Coast (~ -50/00 delta(18)O and -100/00 delta(2)H) and in the Southeast.
      During El Nino periods the precipitation delta(18)O and delta(2)H values are
      lowest in northwest Montana, with precipitation that is depleted in (18)O and
      (2)H extending into northern Colorado, while moisture that is enriched in (18)O
      and (2)H continues to dominate the Gulf Coast. The annual average differences
      between the climate phases generally show especially depleted (18)O and (2)H in
      precipitation across the Rocky Mountain region during El Nino, compared with
      Neutral periods. CONCLUSIONS: Detailed spatial and seasonal patterns of
      delta(18)O, delta(2)H and d-excess values provide fine-scale resolution not
      previously recognized. Climate phases of ENSO have major effects on the spatial
      patterns of delta(18)O, delta(2)H and d-excess values, being especially important
      on a seasonal basis in the Desert Southwest.

PMID- 22847686
TI  - Expression and function of CXCR4 in human salivary gland cancers.
AB  - Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and
      distant organs. Currently, the mechanisms responsible for the metastatic behavior
      of SGC cells are not fully understood. We previously demonstrated that the
      stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is
      involved in the establishment of metastasis in oral squamous cell carcinoma. In
      the present study, we investigated the role of CXCR4 in the metastatic behavior
      of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell
      lines by quantitative RT-PCR and western blotting, respectively. The expression
      of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell
      lines. Functional CXCR4 expression was demonstrated by the ability of these SGC
      cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated
      extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines.
      Immunohistochemical analysis revealed that CXCR4 protein expression was detected
      in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of
      adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid
      carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited
      dramatic metastasis to the lung following intravenous inoculation, whereas
      AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the
      cells, ameliorated body weight loss and improved the survival rate of tumor
      bearing nude mice. These results indicate that CXCR4 expression contributes to
      the metastatic potential of SGCs.

PMID- 22847688
TI  - A liquid chromatography/electrospray ionization tandem mass spectrometric method
      for quantification of asiatic acid from plasma: application to pharmacokinetic
      study in rats.
AB  - RATIONALE: Asiatic acid (AA), a pentacyclic triterpene from Centella asiatica
      (L.) Urban, has shown numerous therapeutic activities. However, none of the
      published works to date has used high-performance liquid chromatography/tandem
      mass spectrometry (HPLC/MS/MS) for determination of AA from biological fluids.
      Therefore, the present paper describes a sensitive HPLC/electrospray ionization
      (ESI)-MS/MS method for quantification of AA in rat plasma. METHODS: Ammonium
      adduct formation of AA was essential in the development of a sensitive method
      with the rat plasma samples being pre-treated by a simple solid-phase extraction
      method. The separation was achieved on a Cosmosil C(18) column using a gradient
      mobile phase flow. Detection was performed using an Applied Biosystems API Q-Trap
      2000 mass spectrometer equipped with an ESI source operated in positive mode with
      colchicine used as internal standard. RESULTS: An eight-point calibration curve
      over the concentration range of 1.02-407.88 ng/mL for AA from rat plasma provided
      an optimum linear detector response (with r(2) >0.9983). The mean percentage
      recovery (n = 3) for the low, middle and high quality control samples was 91.23
      +/- 1.88%, 90.36 +/- 0.55% and 89.71 +/- 0.21%, respectively. The intra-day and
      inter-day precision and accuracy of the quality control samples were within <=5%
      and +/-7% correspondingly. CONCLUSIONS: The developed method was validated as per
      US FDA guidelines and applicability demonstrated by successful measurement of AA
      from plasma following oral administration of C. asiatica extracts to Wistar rats.
      The results suggest that the method could be applied to therapeutic monitoring of
      AA and pharmacokinetic studies in human volunteers.

PMID- 22847689
TI  - An improved CeO2 method for high-precision measurements of 17O/16O ratios for
      atmospheric carbon dioxide.
AB  - RATIONALE: The oxygen isotopic composition of carbon dioxide originating at the
      Earth's surface is modified in the stratosphere by interaction with ozone which
      has anomalous oxygen isotope ratio (Delta(17)O = 1000 * ln(1 + delta(17)O/1000) -
      0.522 * 1000 * ln (1 + delta(18)O/1000) >0). The inherited anomaly provides a
      powerful tracer for studying biogeochemical cycles involving CO(2). However, the
      existing methods are either too imprecise or have difficulty in determining the
      small Delta(17)O variations found in the tropospheric CO(2). In this study an
      earlier published CeO(2) and CO(2) exchange method has been modified and improved
      for measuring the Delta(17)O values of atmospheric carbon dioxide with high
      precision. METHODS: The CO(2) fraction from air samples was separated by
      cryogenic means and purified using gas chromatography. This CO(2) was first
      analyzed in an isotope ratio mass spectrometer, then artificially equilibrated
      with hot CeO(2) to alter its oxygen isotopes mass-dependently and re-analyzed.
      From these data the (17)O/(16)O and (18)O/(16)O ratios were calculated and the
      Delta(17)O value was determined. RESULTS: The validity of the method was
      established in several tests by using artificially prepared CO(2) with zero and
      non-zero Delta(17)O values. The published value of the CO(2)-H(2) O equilibrium
      slope was also reproduced. CONCLUSIONS: The CO(2)-CeO(2) equilibration method has
      been improved to measure the oxygen isotope anomaly (Delta(17)O value) of
      atmospheric CO(2) with an analytical precision of +/-0.120/00 (2sigma).

PMID- 22847690
TI  - The role of ion-bound cluster formation in negative ion mass spectrometry.
AB  - RATIONALE: The ionization mechanisms operative in negative ion atmospheric
      pressure mass spectrometry are far from being properly understood. In an excess
      of oxygen superoxide (O(2)(-)) is generally the primary charge-carrying species
      that is generated. However, subsequent reactions leading to the finally detected
      ion signals remain obscure. METHODS: Since adiabatic expansion induced cluster
      growth and collision-induced dissociation (CID) processes rendered a
      representative sampling of ion distributions present in the source difficult, a
      custom-built thermally sampling time-of-flight mass spectrometer was used for the
      investigations. Using atmospheric pressure laser ionization of toluene as the
      reagent gas, high yields of thermal electrons were observed, but only negligible
      amounts of by-products. Ab initio calculations for individual ion/molecule
      reaction pathways were performed. RESULTS: Electron capture by molecular oxygen
      resulted in the formation of subsequent superoxide water clusters as well as
      distinct analyte-adduct ions. By adjusting the extent of CID within the ion
      optical stages of the mass spectrometer, the cluster distribution changes to
      smaller cluster sizes and the analyte signals strongly shifted towards M(-) or [M
      H](-). The observed superoxide water cluster distribution was close to thermal.
      The theoretical results confirmed the experimental findings. CONCLUSIONS: In
      negative atmospheric pressure mass spectrometry the water concentration in the
      ion source (determining the ionization efficiency) and the CID energy provided
      through electrical fields (determining the ion distribution) are primary,
      critical parameters for the observed overall ionization mechanism and efficiency.

PMID- 22847691
TI  - Effect of 13C enrichment and sugar type on analysis of sugars by gas
      chromatography/combustion/isotope ratio mass spectrometry.
AB  - RATIONALE: The objective of this investigation was to test gas-chromatographic
      compound-specific analysis for studies on the isotopic composition of (13)C
      enriched sugar molecules. The effects of (13)C enrichment and type of sugar (C5,
      C6) will provide valuable information on isotopic correction for future studies
      employing (13)C-enriched sugars. METHODS: Five sugar solutions of xylose, mannose
      and glucose with (13)C enrichments ranging between 1.1 and 1.5 atom-% were
      prepared. The (13)C enrichments of the initial sugars were measured by elemental
      analyser/isotope ratio mass spectrometry (EA/IRMS); (13)C enrichments for
      derivatised sugars were obtained by gas chromatography/combustion/IRMS
      (GC/C/IRMS). RESULTS: The linear relationships between the (13)C enrichments of
      the initial sugars and the values for the derivatised sugars were sugar-type
      dependent. Corrections for GC/C/IRMS values took into account the kinetic isotope
      effect (KIE) of the derivatising agent associated with the coefficient (K(d)) and
      a newly introduced second coefficient (K(c)) associated with the KIE of the
      sugar. While K(d) was constant, K(c) varied with sugar type. During
      derivatisation acetate groups with (12)C and sugars with more (13)C reacted
      faster. CONCLUSIONS: Coefficients for the specific ranges of (13)C enrichments
      under study have to be assessed and the reactions of different sugar types have
      to be taken into account to avoid underestimation of (13)C enrichment of up to 9%
      (C5) or overestimation of up to 4% (C6).

PMID- 22847692
TI  - Quantification of glycopeptides by multiple reaction monitoring liquid
      chromatography/tandem mass spectrometry.
AB  - Protein glycosylation has a major influence on functions of proteins. Studies
      have shown that aberrations in glycosylation are indicative of disease
      conditions. This has prompted major research activities for comparative studies
      of glycoproteins in biological samples. Multiple reaction monitoring (MRM) is a
      highly sensitive technique which has been recently explored for quantitative
      proteomics. In this work, MRM was adopted for quantification of glycopeptides
      derived from both model glycoproteins and depleted human blood serum using glycan
      oxonium ions as transitions. The utilization of oxonium ions aids in identifying
      the different types of glycans bound to peptide backbones. MRM experiments were
      optimized by evaluating different parameters that have a major influence on
      quantification of glycopeptides, which include MRM time segments, number of
      transitions, and normalized collision energies. The results indicate that oxonium
      ions could be adopted for the characterization and quantification of
      glycopeptides in general, eliminating the need to select specific transitions for
      individual precursor ions. Also, the specificity increased with the number of
      transitions and a more sensitive analysis can be obtained by providing specific
      time segments. This approach can be applied to comparative and quantitative
      studies of glycopeptides in biological samples as illustrated for the case of
      depleted blood serum sample.

PMID- 22847693
TI  - Metabolism profile of timosaponin B-II in urine after oral administration to rats
      by ultrahigh-performance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry.
AB  - RATIONALE: Timosaponin B-II (TB-II) is one of the major bioactive steroid
      glycosides isolated from Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has
      been regarded as a potential lead compound, which may be further developed into a
      promising new drug for preventing dementia. To fully understand the action
      mechanism of TB-II, it is important to study the metabolism profile of this
      compound in vivo. METHODS: Herein, a rapid and sensitive method based on
      ultrahigh-performance liquid chromatography (UHPLC)/quadrupole-time-of-flight
      mass spectrometry (QTOFMS) was established to comprehensively investigate the
      metabolism of TB-II in Sprague-Dawley rat urine following oral administration of
      a single dose of TB-II at 500.4 mg.kg(-1). RESULTS: A total of twelve metabolites
      were detected and identified by means of comparing molecular mass, retention time
      and spectral pattern of the analytes with those of the parent drug. A possible
      metabolic pathway on the biotransformation of TB-II was also investigated and
      proposed. CONCLUSIONS: Oxidation, deglycosylation and E-ring cleavage were found
      to be the major metabolic processes of the compound in rat. It is the first
      report on a mammalian metabolism study of timosaponin, a common member of steroid
      glycosides, in rat urine.

PMID- 22847695
TI  - Electrospray ionisation mass spectrometric studies for the determination of
      palladium after pre-concentration by disposable pipette extraction.
AB  - RATIONALE: Electrospray ionisation mass spectrometric (ESI-MS) analysis of Pd in
      complex matrices is difficult due to the multiplicity of matrix effects. Two
      different approaches, internal standard and matrix separation, were investigated
      for developing a reliable analytical procedure for the trace level determination
      of Pd in simulated high-level liquid waste (SHLLW) solutions. METHODS: An ESI
      mass spectrometer with a quadrupole-time-of-flight analyser was used to study the
      speciation of the palladium-benzoylthiourea (Pd-BTU) complex and to determine the
      Pd content. The Pd-BTU complex was selectively pre-concentrated using disposable
      pipette extraction (DPX). Extraction parameters as well as ESI-MS parameters such
      as concentration of BTU, acidity, composition of medium and capillary voltage,
      etc., were optimized based on the major species [Pd(BTU)(2)S](+). RESULTS: The
      method gave quantitative and selective pre-concentration of the Pd-BTU complex
      from SHLLW. Linearity from 5 ppb to 200 ppb and a limit of detection of 0.012 ppb
      were obtained for Pd. No interference from the neighboring elements, viz.
      ruthenium, rhodium, silver and cadmium, was observed during the determination of
      Pd based on the [Pd(BTU)(2)S](+) peak. The ESI signal intensity was not
      influenced by the presence of the many other elements in the SHLLW solution.
      CONCLUSIONS: Good sensitivity, tolerance to matrix concentration and the absence
      of interference from neighboring elements make the method very promising for the
      determination of Pd at low levels in complex samples. We have demonstrated the
      capability of ESI-MS for the quantification of Pd in complex matrices and its
      potential for providing data on speciation, using the Pd-BTU complex.

PMID- 22847694
TI  - Mass spectrometric analysis of novel phosphorylation sites in the TRPC4beta
      channel.
AB  - RATIONALE: The transient receptor potential canonical (TRPC) channel 4beta is a
      non-selective cation channel that is regulated by intracellular Ca(2+) and G
      protein-coupled receptors. Tyrosine phosphorylation of TRPC4beta is important in
      mediating the activity and membrane expression of this channel protein. However,
      studies of TRPC4beta Ser/Thr phosphorylation are lacking. METHODS: To investigate
      the phosphorylation sites involved in regulating the diverse functions of
      TRPC4beta in mammalian cells, we used nano-liquid chromatography/tandem mass
      spectrometry to identify key phosphorylation sites in TRPC4beta that was
      immunopurified from HEK293 cells with monoclonal anti-TRPC4beta antibody.
      RESULTS: We identified four phosphorylation sites in the C-terminus of TRPC4beta,
      none of which had been previously reported. Our data show that TRPC4beta in
      mammalian cells is highly phosphorylated under basal conditions at multiple
      sites, and that a mass spectrometric proteomic technique combined with antibody
      based affinity purification is an effective approach to define the
      phosphorylation sites of TRPC4beta channels in mammalian cells. CONCLUSIONS:
      These novel phosphorylation sites on TRPC4beta may play a potential role in the
      phosphorylation-mediated regulation of TRPC4beta channel activity and function in
      mammalian cells.

PMID- 22847696
TI  - Oxygen isotopic composition of fulgurites from the Egyptian Sahara and other
      locations.
AB  - RATIONALE: Fulgurites are glassy crusts or hollow glassy tubes formed by the
      impact of a lightning strike on a target material on the Earth's surface. The
      oxygen isotopic composition of fulgurites has never been measured and,
      consequently, it is unknown whether or not isotopic fractionations take place
      between the target material and the fulgurite glass during the lightning event
      which is an excellent natural example of extremely fast melting process. METHODS:
      Following well-established procedures (high-temperature reaction of the fulgurite
      material with BrF(5), conversion into CO(2) of the evolved O(2) and measurement
      of the(18)O/(16)O ratio on a Finnigan Delta S mass spectrometer) we measured for
      the first time the oxygen isotopic composition of sets of fulgurites coming from
      various locations on the Earth's surface. RESULTS: The range of isotopic values
      is quite large, probably reflecting the oxygen isotopic values of the target
      materials. In the case of fulgurites from the Sahara Desert the isotopic values
      obtained from the bulk material, quartz crystals sticking to the fulgurite body,
      tiny samples of loose sand coming from fulgurite bubbles, and sand samples
      collected near the fulgurites, are very close to one another. CONCLUSIONS:
      Although we do not have indisputable evidence, we conclude that, at least in the
      case of oxygen, the fusion process of the material struck by lightning, as well
      as all the extremely fast high-temperature fusion processes, probably take place
      without any isotopic fractionation effect.

PMID- 22847697
TI  - Isomeric differentiation of polycyclic aromatic hydrocarbons using silver nitrate
      reactive desorption electrospray ionization mass spectrometry.
AB  - RATIONALE: Polycyclic aromatic hydrocarbons (PAHs) are nonpolar and difficult to
      detect by desorption electrospray ionization. We present a new detection method
      based on cationization with silver ions, which has the added advantage of being
      able to differentiate PAHs with the same mass but different structure. METHODS:
      9,10-Diphenylanthracene and triptycene, in addition to four different groups of
      PAH isomers: (1) anthracene and phenanthrene, (2) pyrene and fluoranthene, (3)
      benz[a]anthracene, benz[b]anthracene (tetracene), and chrysene (4) benzo[a]pyrene
      and benzo[k]fluoranthene, were deposited on a paper surface and bombarded with
      methanol droplets containing silver nitrate. The resulting microdroplets entered
      a quadruple mass spectrometer for mass analysis. RESULTS: The mass spectrum shows
      [PAH](+), [Ag + OH + PAH](+), and [Ag(PAH)(n)](+) (n = 1, 2) (and [PAH + O(2)](+)
      in the case of benz[b]anthracene) ions. PAHs having a bay structure, such as
      phenanthrene, showed a different tendency to interact with silver ions from those
      PAHs having a linear arrangement of the fused benzene rings, such as anthracene.
      The ratios of the [PAH](+) peak intensity to that of [Ag-PAH](+), [Ag + OH +
      PAH](+), [Ag(PAH)(2)](+), and [PAH + O(2)](+) were used to differentiate the PAH
      isomers sharing the same molecular formula with different structures. For
      isomeric mixtures the [PAH](+) to [Ag + OH + PAH](+) ratio was found to be the
      most useful parameter. The uncertainty in the mole fraction of an isomeric
      mixture was +/-0.09, +/-0.13, +/-0.25, and +/-0.1 for phenanthrene-anthracene,
      fluoranthene-pyrene, benz[a]anthracene-chrysene, and benzo[a]pyrene
      benzo[k]fluoranthene, respectively. CONCLUSIONS: A simple method has been
      developed for the detection of PAHs in desorption electrospray ionization mass
      spectrometry based on Ag(I) cationization. The method showed a capability to
      differentiate PAHs isomers (having the same molecular mass) in isomeric mixture
      with an uncertainty in the mole fraction of about +/-0.1. At high inlet
      temperature and voltage, this method showed better sensitivity but less ability
      to differentiate between isomeric species.

PMID- 22847698
TI  - Identification, quantification and carbon stable isotopes determinations of
      organic acids in monofloral honeys. A powerful tool for botanical and
      authenticity control.
AB  - RATIONALE: The analytical composition and botanical origin of honey are basic
      data used to determine the quality of this foodstuff. Although proteins are used
      to characterise the analytical composition of honey, they can be eliminated
      during its ultrafiltration and, in the case of honeys not saturated with their
      own pollen, the use of proteins does not work well. As acidity is a well-known
      characteristic of honey and organic acids are present at around 0.5% in honey, we
      therefore investigated an alternative method to the protein-based White method,
      using organic acids as new internal standards instead of proteins. METHODS: The
      qualitative and quantitative analyses of 14 organic acids were carried out by ion
      chromatography with an electrochemical detector. The (13)C/(12)C isotopic ratios
      of the honeys, and of the organic acids extracted from them with an anion
      exchange resin, were determined by isotope ratio mass spectrometry. RESULTS:
      Gluconic acid is the predominant organic acid in honey, at between 1.8 and 12.7
      g/kg. For fir honey the major acid is galacturonic acid at around 4.6 g/kg. The
      isotopic ratios of honeys and of their acids are strongly linked. Correlations
      between the delta(13)C values of the honey and the acids were significant, and
      better than those obtained using proteins. CONCLUSIONS: This study has provided a
      method to differentiate honeys from seven botanical origins, based on organic
      acid analysis. By combining various organic acid contents and isotopic ratio
      values through statistical processing by Principal Component Analysis it is
      possible to differentiate honey samples as a function of their botanical origin.

PMID- 22847699
TI  - Continuous flow reaction monitoring using an on-line miniature mass spectrometer.
AB  - RATIONALE: A recently developed miniature electrospray ionisation mass
      spectrometer has been coupled to a preparative flow chemistry system in order to
      monitor reactive intermediates and competing reaction paths, screen starting
      materials, and optimise reaction conditions. Although ideally suited to the
      application, mass spectrometers have rarely been used in this way, as traditional
      instruments are too bulky to be conveniently coupled to flow chemistry platforms.
      METHODS: A six-port switching valve fitted with a 5 MUL loop was used to
      periodically sample the flow stream leaving the reactor coil. Mass spectra
      corresponding to the sample loop contents were observed approximately 10 s after
      activating the valve. High fluidic pressure was maintained throughout to ensure
      that gaseous products remained in solution. As an illustrative example of how
      this apparatus can be employed, the generation of benzyne and its subsequent
      reaction with furan were investigated. Benzyne was prepared via diazotisation of
      anthranilic acid using tert-butyl nitrite. RESULTS: Unexpectedly, the explosive
      diazotised intermediate was detected by the mass spectrometer at low coil
      temperatures or short residence times. The optimum reactor temperature and
      residence time for production of the desired Diels-Alder product are 50  degrees
      C and 3-5 min, respectively. There are competing reaction pathways leading to the
      formation of acridone and several other by-products. CONCLUSIONS: On-line mass
      spectrometry allowed the flow conditions to be quickly tuned for safe operation
      and optimal generation of the desired product. The validity of this approach was
      corroborated by off-line liquid chromatography/mass spectrometry (LC/MS) analysis
      of flow samples.

PMID- 22847700
TI  - Characterization of lipid A profiles from Shigella flexneri variant X
      lipopolysaccharide.
AB  - RATIONALE: In developing countries, Shigella flexneri (Sf) is the major causative
      agent of the endemic shigellosis (bacillary dysentery) responsible annually for
      one million fatalities mostly among infants. Lipopolysaccharides (LPSs) are
      characteristic components of the outer membrane of the overwhelming majority of
      Gram-negative bacteria. Since lipid A is essential for the viability of the Gram
      negative bacteria, it is subject to extensive chemical studies with new
      analytical techniques. METHODS: Lipid A was released by mild acid hydrolysis from
      the lipopolysaccharide which was obtained via the phenol/water extraction,
      purified and analyzed by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) and matrix-assisted laser
      desorption/ionization laser-induced dissociation tandem mass spectrometry (MALDI
      LID-MS/MS). RESULTS: A detailed structural study of the whole lipid A obtained
      from S. flexneri variant X was carried out for the first time. Thus, we have
      shown that lipid A is a heterogeneous mixture having different numbers of
      acylated and phosphoethanolamine groups attached to the diglucosamine backbone.
      Furthermore, we found in the phenol phase an unusual hepta-acylated lipid A
      species, although the abundance was very low. CONCLUSIONS: MALDI-TOF-MS allowed
      us to unravel the lipid A heterogeneity, which was not previously reported in Sf
      LPS. It is well known that slight variations of the chemical structure of lipid A
      may change its biological activity. Thus, the knowledge of the detailed chemical
      structure represents an essential step for further development of new preventive
      or therapeutically active compounds.

PMID- 22847701
TI  - Absorption-mode spectra on the dynamically harmonized Fourier transform ion
      cyclotron resonance cell.
AB  - RATIONALE: The recently designed dynamically harmonized Fourier transform ion
      cyclotron resonance (FT-ICR) cell creates a more harmonized electric field for
      the detection of the cyclotron motion of ions and prolongs the ion transient from
      seconds to minutes. In order to achieve its best performance, phase correction
      was applied in the spectra, and new advantages of the absorption-mode were
      revealed. METHODS: Spectra were acquired from both simple standard and complex
      mixtures using either narrowband or broadband mode, and the data were processed
      to compare the performance of the spectra in magnitude and absorption-mode.
      RESULTS: The research shows that phase correction works well with data from
      Nikolaev's new cell, which produces the maximum improvement in resolving power
      (2*), and improves the match with the theoretical intensities of the isotopic
      peaks. In addition, the harmonic peaks can be diagnosed immediately in the
      absorption-mode. CONCLUSIONS: The manuscript demonstrates absorption-mode spectra
      from Nikolaev's ICR cell, which will be of interest to the community. The
      improved relative peak intensities and immediate identification of harmonic peaks
      will facilitate data interpretation.

PMID- 22847702
TI  - High-expression EGFR/cell membrane chromatography-online-high-performance liquid
      chromatography/mass spectrometry: rapid screening of EGFR antagonists from Semen
      Strychni.
AB  - RATIONALE: Traditional methods for screening active compounds from complex system
      such as traditional Chinese medicines are relatively cumbersome and time
      consuming. In order to improve this situation, we established an online
      analytical method for screening, separation and identification EGFR antagonists
      from traditional Chinese medicines, which is described in this study. METHODS:
      Cells with high EGFR expression levels were used to prepare the cell membrane
      stationary phase for the EGFR cell membrane chromatography model with the purpose
      of screening active compounds. Separation of the retention fractions was achieved
      by the high-performance liquid chromatography, and identification was conducted
      via electrospray ionization quadrupole mass spectrometry. The inhibitory effects
      of active compounds on EGFR cell growth were also demonstrated in vitro. RESULTS:
      The screening results showed that vauquline and strychnine from Semen Strychni
      could be active components acting on EGFR similarly to gefitinib as a control
      drug. Results from biological trials showed that vauquline and strychnine
      inhibited cell proliferation of HEK293/EGFR cells, and inhibited Erk
      phosphorylation, and can effectively reduce expression of downstream signaling
      molecules. CONCLUSIONS: This EGFR cell membrane chromatography-online-high
      performance liquid chromatography/tandem mass spectrometry method can be applied
      for rapid screening, separation and identification of EGFR antagonists from
      traditional Chinese medicines and should be useful for drug discovery with
      natural medicinal herbs.

PMID- 22847703
TI  - Structural identification by differential mass spectrometry as a criterion for
      selecting the best quantum chemical calculation of formation enthalpy for
      tetrachlorinated biphenyls.
AB  - RATIONALE: The assignment of correct structures for isomers with similar mass
      spectra (e.g. polyhalogenated aromatic compounds) is not always successful when
      spectral libraries alone are employed or, even worse, when the compounds are not
      present in commercial spectral libraries. METHODS: We present a computational
      method based on differential mass spectrometry (Diff-MS) for the validation of
      formation enthalpy (Delta(f)H) series calculated using quantum chemistry for the
      fragments produced in electron ionization (EI)-MS. The method simulates the
      chemical structure identification (CSI) of isomers with similar mass spectra
      using differential mass spectra and Delta(f)H series. The best Delta(f)H values
      were those from which the correct structures could be derived. RESULTS: We have
      used six tetrachlorinated biphenyl isomers (TeCBs 44, 46, 52, 66, 74, 77). Their
      EI mass spectra were acquired at 70 eV and, for the principal ions, five series
      of Delta(f) H values were computed by the semi-empirical methods, AM1, MINDO3,
      MNDO, PM3, and RM1. The generation of differential mass spectra and the
      correlation with the Delta(f)H series for the calculation of probabilities from
      the list of structural assignments were carried out with the ordering algorithm
      (ORD) of the CSI-Diff-MS Data Analysis 3.1.1 program. CONCLUSIONS: Intelligent
      software, used for structural elucidation based on MS and QCC, was employed to
      select the best values of the formation enthalpies of TeCBs. The advantages and
      disadvantages of the semi-empirical methods for the calculation of Delta(f)H
      values for different TeCB ions are critically presented. The best semi-empirical
      methods were RM1, AM1 and MINDO3, which can be used to calculate the Delta(f)H
      database necessary to identify TeCB isomers. This approach allowed the correct
      assignment of structures for isomers with very similar mass spectra and
      demonstrated the reliability of the correlation between differential mass spectra
      and the formation enthalpies of the fragment ions.

PMID- 22847704
TI  - Colloidal TiO2 nanoparticles as substrates for M(S)ALDI mass spectrometry of
      transition metal complexes.
AB  - RATIONALE: Nanoparticles as substrates for matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) have
      advantages over organic matrices, since they enable acquisition of spectra in the
      low-mass range. It has been previously shown that TiO(2) nanoparticles can be
      used as substrate for MALDI-TOF MS analysis of phospholipids and for other types
      of molecules, but none of them was applied to the analysis of transition metal
      complexes. METHODS: The MALDI-TOF mass spectra of potential anti-tumor drugs
      [AuCl(2)(bipy)]Cl, [PtCl(4)(bipy)], and [RuCl(2)(bipy)(2) ]Cl acquired with
      organic matrices have been compared with spectra acquired with colloidal titanium
      dioxide nanoparticles. Colloidal TiO(2) nanoparticles (NPs) with average diameter
      of 5 nm were synthesized and characterized by microscopy. For some experiments,
      the TiO(2) NPs were treated at 60  degrees C. Suspensions of matrix and the
      analyte were premixed, applied to the MALDI target and left at room temperature.
      Mass spectra were acquired with a 50-Hz pulsed nitrogen laser emitting at a
      wavelength of 337 nm. RESULTS: The MALDI spectra of transition metal complexes
      acquired with TiO(2) NPs exhibited somewhat lower sensitivity than those with
      organic matrices; on the other hand, they are characterized by significantly
      lower number of signals arising from the tested complexes than the organic
      matrices. Whereas adducts between organic matrices and the analytes were
      detectable in the spectra, this was not the case for the TiO(2)-assisted mass
      spectra. CONCLUSIONS: We have shown that colloidal TiO(2) NPs can be used as
      substrates for MALDI-TOF MS of transition metal complexes. Although the
      sensitivity of this approach in comparison with the use of organic matrices might
      still be a problem, the potential of the applications of NPs for the mass
      spectrometric characterization of transition metal complexes is clearly
      demonstrated.

PMID- 22847705
TI  - Development of liquid chromatography/mass spectrometry based screening assay for
      PfTrxR inhibitors using relative quantitation of intact thioredoxin.
AB  - RATIONALE: Plasmodium falciparum (Pf) thioredoxin reductase (TrxR) catalyzes the
      reduction of thioredoxin disulfide (Trx-S(2)) to thioredoxin dithiol (Trx
      (SH)(2)) that is essential for antioxidant defense mechanism and DNA synthesis in
      the parasite and is a validated drug target for new antimalarial agents. METHODS:
      In this study, we have developed a liquid chromatography/mass spectrometry
      (LC/MS)-based functional assay to identify inhibitors of PfTrxR by quantifying
      the product formed (Trx-(SH)(2)) in the enzymatic reaction. Relative quantitation
      of the reaction product (intact Trx-(SH)(2)) was carried out using an Agilent
      6520 QTOF mass spectrometer equipped with a positive mode electrospray ionization
      (ESI) source. RESULTS: The calibration curve prepared for Trx-(SH)(2) at
      concentrations ranging from 1.8 to 116.5 ug/mL was linear (R(2) >0.998). The
      limit of detection (LOD) and limit of quantification (LOQ) of Trx-(SH)(2) were at
      0.45 and 1.8 ug/mL respectively. To validate the developed functional assay we
      have screened reference compounds 1, 2 and 3 for their PfTrxR inhibitory activity
      and ten natural compounds (at 10 MUM) which were earlier identified as ligands of
      PfTrxR by a UF-LC/MS based binding assay. CONCLUSIONS: The developed LC/MS-based
      functional assay for identification of inhibitors of PfTrxR is a sensitive and
      reliable method that is also amendable for high-throughput format. This is the
      first representation of a relative quantitation of intact Trx-(SH)(2) using
      LC/MS.

PMID- 22847706
TI  - Characterization of ethanolysis products of poly(dimethylsiloxane) species by
      electrospray ionization tandem mass spectrometry.
AB  - RATIONALE: The partial and controlled degradation of insoluble cross-linked
      silicon-based polymers is a promising approach to enable their characterization
      by mass spectrometry. Providing that the chemolysis reaction specifically
      proceeds at cross-linking sites, the size of linear poly(dimethylsiloxane)s
      (PDMS) produced during the treatment should reflect the length of linear segments
      between branching points in the original network. In this context, the
      specificity of ethanol to act as a nucleophilic agent towards tri-functional
      silicon atoms in a D3TD(n)TD3 model was evaluated. METHODS: Tandem mass
      spectrometry (MS/MS) combined with accurate mass measurements, MS(3) experiments
      and collision-induced dissociation of authentic compounds was used for structural
      characterization of D3TD(n)TD3 ethanolysis products. All MS/MS data were obtained
      from electrosprayed ammonium adducts, previously reported to provide the most
      informative data for silicon-based polymers. RESULTS: Since the expected
      ethanolysis products were hydroxy- and ethoxy-terminated PDMS, the dissociation
      behavior of such polymeric species was established, using electrosprayed ammonium
      adducts as the precursor ions. Diagnostic product ions were identified, allowing
      four main D3TD(n)TD3 ethanolysis products to be structurally characterized. End
      group analysis of these polymeric distributions clearly indicated that
      ethanolysis was mostly occurring on tri-functional silicon atoms but also, to a
      lesser extent, on those D atoms close to T silicons. CONCLUSIONS: The size of the
      linear skeleton located between two tri-functional silicon atoms could be
      accurately determined by mass spectrometric analyses of a polymeric model
      submitted to ethanolysis. This soft and rapid pre-treatment is thus a promising
      approach for determining the length of linear segments between branching points
      in the original network of cross-linked silicon-based polymers.

PMID- 22847707
TI  - Performance and geometry optimization of the ceramic-based rectilinear ion traps.
AB  - RATIONALE: The rectilinear ion trap (RIT), as a simplified linear ion trap, has
      shown great potential in the field of portable mass spectrometers for its simple
      structure and easy manufacture. In this study, the new ceramic-based rectilinear
      ion trap (cRIT) was constructed, and the performance and geometry optimization of
      a series of cRITs were examined. METHODS: Gold-plated zirconia ceramic electrodes
      were used to build the cRITs. A home-built electrospray ionization mass
      spectrometry (ESI-MS) platform was used to test the properties of the cRITs. The
      protonated ions of arginine (m/z 175) and reserpine (m/z 609) were produced in
      the experiments by ESI. RESULTS: A series of cRITs with different geometries were
      constructed, and the overall mechanical accuracy of all parts and the cRIT
      assembly is within ~10 um. The mass resolution, the first stability diagram and
      the tandem mass (MS/MS) analysis capability were tested. For a 6 mm * 5 mm cRIT,
      the mass resolution was higher than 1800 at m/z 609 when the scan speed was 2190
      Th/s. A MS/MS capability with a ca. 94.8% CID efficiency on the cRIT 6 * 5 was
      obtained. CONCLUSIONS: The ceramic-based rectilinear ion trap (cRIT) can be a
      qualified linear ion trap mass analyzer with high ion storage capability,
      excellent mass resolution, and high tandem mass analysis efficiency. It can be
      easily manufactured and operated, and has great potential in ion trap mass
      spectrometry.

PMID- 22847708
TI  - Classification and characterization of unknown cytokinins into essential types by
      in-source collision-induced dissociation electrospray ionization ion trap mass
      spectrometry.
AB  - RATIONALE: Mass spectrometry is effective for determination of cytokinins, which
      are bioactive compounds with an adenine-core structure. However, it is difficult
      to characterize any cytokinin compound without the relevant standard or known
      molecular structure information. With a limited number of standards, an in-source
      collision-induced dissociation (CID) method for characterization and
      classification of unknown cytokinins was described in this study. METHODS:
      Cytokinins were separated by high-performance liquid chromatography and then
      analyzed by electrospray ionization ion trap mass spectrometry using an in-source
      CID technique and multiple reaction monitoring (MRM) mode. RESULTS: Based on the
      properties of multi-stage fragmentation in mass spectrometry, naturally occurring
      cytokinins were classified into four types (zeatin, dihydrogen zeatin,
      isopentenyl adenine and benzyl adenine) by losing their conjugated sugar, sugar
      phosphate and other substituents in the source region. Following this technique,
      seven unknown cytokinins were characterized from roots of maize (Zea mays)
      without standards and one of them was finally confirmed to be cis-zeatin
      riboside. CONCLUSIONS: An in-source CID technique combined with MRM mass
      spectrometry was developed to provide product ion information for identification
      of cytokinins and to afford guidance for the discovery of unknown cytokinins.

PMID- 22847709
TI  - Influence of dissolved ions on determination of oxygen isotope composition of
      aqueous solutions using the CO2-H2O equilibration method.
AB  - RATIONALE: Stable isotope compositions of natural waters, such as seawater,
      glaciers and basinal brines, can provide valuable information about Earth's
      hydrological cycle and its evolutionary history. However, a high concentration of
      dissolved ions in some natural waters hinders an accurate analysis of their
      oxygen isotope composition. A laboratory study was carried out in order to
      provide guidelines on how to resolve this analytical difficulty. METHODS: CO(2)
      gas was equilibrated with saline aqueous solutions of various chemical
      compositions at 25  degrees C. Subsequently, the oxygen isotope composition of
      the CO(2) was determined at different equilibration times using a dual-inlet
      isotope ratio mass spectrometer in order to evaluate the oxygen isotope salt
      effect and the rate of oxygen isotope exchange between CO(2) and the saline
      solution. RESULTS: Using the experimentally determined oxygen isotope salt
      effects of aqueous chloride and sulfate solutions, an empirical method for the
      prediction of the oxygen isotope salt effect of a 1.0 molal chloride or sulfate
      solution was proposed. The rates of oxygen isotope exchange between CO(2) and
      saline solutions were also examined. Our experimental data indicates that the
      sequence of the oxygen isotope exchange time is as: MgSO(4) > CaCl(2) ~
      Na(2)SO(4) > NaCl > MgCl(2) > KCl > H(2)O. CONCLUSIONS: The isotope salt effect
      and the kinetics of isotope exchange must be taken into account when the oxygen
      isotope composition of a saline aqueous solution is determined using the CO(2)
      H(2)O equilibration method. Our experimental data and the proposed prediction
      method provide essential guidelines for the accurate delta(18)O analysis of
      saline aqueous solutions.

PMID- 22847710
TI  - Low-energy electron interactions with tungsten hexacarbonyl--W(CO)6.
AB  - RATIONALE: Low-energy secondary electrons are formed when energetic particles
      interact with matter. High-energy electrons or ions are used to form metallic
      structures from adsorbed organometallic molecules like W(CO)(6) on surfaces. We
      investigated low-energy electron attachment to W(CO)(6) in the gas phase to
      elucidate possible reactions during surface modification. METHODS: Two crossed
      electron/molecular beam setups were utilised: (i) a high-resolution electron
      monochromator combined with a quadrupole mass spectrometer which was used for the
      measurement of relative cross sections as a function of the electron energy, and
      (ii) a double focusing mass spectrometer used for measurements of metastable
      decays of anions. RESULTS: The study was performed in the electron energy range
      between ~0 and 14 eV. W(CO)(6) efficiently decomposed upon attachment of a low
      energy electron and no stable W(CO)(6)(-) anion was observed on mass
      spectrometric time scales. The transient negative ion formed lost instead
      sequentially CO ligands. The fragment anions W(CO)(5)(-), W(CO)(4)(-), W(CO)(3)(
      ), and W(CO)(2)(-) were observed. However, no W(-) was detectable. CONCLUSIONS:
      Dissociative electron attachment (DEA) to W(CO)(6) led to strong dissociation but
      a complete loss of all CO ligands was not observed in DEA. Deposit contaminations
      might be a direct result of DEA reactions close to the irradiation spot in beam
      deposition techniques.

PMID- 22847711
TI  - Pre-processing of Orbitrap higher energy collisional dissociation tandem mass
      spectra to reduce erroneous iTRAQ ratios.

PMID- 22847712
TI  - Effectiveness of a recovery-orientated psychiatric intervention package on the
      wellbeing of people with early dementia: a preliminary randomised controlled
      trial.
AB  - OBJECTIVE: To investigate whether recovery-orientated psychiatric assessment and
      therapeutic intervention enhances the wellbeing of people with dementia and their
      family carers. METHODS: In a preliminary randomised controlled trial, 48 people
      with early dementia were recruited. Of 34 who completed the trial, 17 were in the
      recovery and 17 in the treatment as usual group. Recovery participants received a
      recovery-focused pre-diagnostic wellbeing assessment and counselling, diagnostic
      consultation with written feedback and post-diagnostic support over a period of 6
      months using the WHO Wellbeing Index as the primary measure, and Mini Mental
      State Examination, Cornell Scale for Depression in Dementia, EUROQOL and Zarit
      Burden Interview as secondary outcome measures. RESULTS: People in the recovery
      group showed a significant improvement in the WHO Wellbeing Index (18.3 for
      recovery vs 9.46 for treatment as usual; t = -2.28, p = 0.03), with trends of
      improvement in other outcome measures. CONCLUSIONS: This trial shows that a
      recovery-focused diagnostic consultation and post-diagnostic support enhance the
      wellbeing of people with mild cognitive impairment and early dementia.

PMID- 22847713
TI  - Three approaches to investigating functional compromise to the default mode
      network after traumatic axonal injury.
AB  - The default mode network (DMN) is a reliably elicited functional neural network
      with potential clinical implications. Its discriminant and prognostic utility
      following traumatic axonal injury (TAI) have not been previously investigated.
      The present study used three approaches to analyze DMN functional connectedness,
      including a whole-brain analysis [A1], network-specific analysis [A2], and
      between-node (edge) analysis [A3]. The purpose was to identify the utility of
      each method in distinguishing between healthy and brain-injured individuals, and
      determine whether observed differences have clinical significance. Resting-state
      fMRI was acquired from 25 patients with TAI and 17 healthy controls. Patients
      were scanned 6-11 months post-injury, and functional and neurocognitive outcomes
      were assessed the same day. Using all three approaches, TAI subjects revealed
      significantly weaker functional connectivity (FC) than controls, and binary
      logistic regressions demonstrated all three approaches have discriminant value.
      Clinical outcomes were not correlated with FC using any approach. Results suggest
      that compromise to the functional connectedness of the DMN after TAI can be
      identified using resting-state FC; however, the degree of functional compromise
      to this network, as measured in this study, may not have clinical implications in
      chronic TAI. 

PMID- 22847714
TI  - Towards a solution for performance related confounds: frontal, striatal and
      parietal activation during a continuous spatiotemporal working memory
      manipulation task.
AB  - Working memory plays a role in various forms of psychopathology. However, working
      memory consists of multiple theoretical components that may be differently taxed
      by various specific types of task, and brain activation differences between
      patients and healthy controls may result from differences in task performance.
      This makes it difficult to interpret such results in terms of disease-related
      dysfunctions in affected regions or networks. The aim of the current study was to
      determine the brain activation related to the updating of spatiotemporal content
      of working memory, in such a way that performance-related confounds in future
      clinical studies would be minimized. Nineteen healthy volunteers performed a task
      involving a continuous updating process during fMRI measurement. A frontostriatal
      network including medial and lateral prefrontal cortex, inferior frontal cortex,
      premotor cortex, supplementary motor cortex, thalamus and putamen was found to be
      related to the updating process. The results constrain the set of brain regions
      plausibly related to the specific updating component of working memory. Further,
      the task design may be of use in future studies of pathological conditions such
      as schizophrenia due to the minimization of potential confounds.

PMID- 22847715
TI  - Squaramide-catalysed enantio- and diastereoselective sulfa-Michael addition of
      thioacetic acid to alpha,beta-disubstituted nitroalkenes.
AB  - A highly enantio- and diastereoselective sulfa-Michael addition of thioacetic
      acid to alpha,beta-disubstituted nitroalkenes catalysed by a chiral squaramide
      organocatalyst has been described. This organocatalytic reaction at an extremely
      low catalyst loading (0.2 mol%) furnished synthetically useful beta-nitro
      sulfides in excellent yields with good diastereoselectivities and high
      enantioselectivities (up to 94 : 6 dr, 95% ee). In addition, the catalytic
      reaction can be performed on a 10 gram scale, and facile transformation into
      taurine derivative is also presented.

PMID- 22847719
TI  - Imageable antigen-presenting gold nanoparticle vaccines for effective cancer
      immunotherapy in vivo.

PMID- 22847720
TI  - Photodynamic therapy as an alternative treatment for disinfection of bacteria in
      oral biofilms.
AB  - BACKGROUND AND OBJECTIVES: Biofilm-related diseases such as caries and
      periodontal disease are prevalent chronic oral infections which pose significant
      oral and general health risks. Biofilms are sessile communities attached to
      surfaces. Photodynamic therapy (PDT) has been demonstrated to have a significant
      anti-microbial effect and presents as an alternative to treating biofilm-related
      disease. The aim of this study was to determine the ability of porfimer sodium
      induced PDT to treat localized infections of Streptococcus mutans in biofilm
      communities. MATERIALS AND METHODS: Reproducible biofilms were formed by S.
      mutans strain ATCC 27351 growing in log phase at 37 degrees C in Brain Heart
      Infusion medium, circulating through flow cells at 3 ml/minute for 36-48 hours.
      The photosensitizer used was porfimer sodium (Photofrin(r)) at 125 ug/ml with
      biofilm immersion times of 5 minutes and increasing energy density of post
      immersion laser illumination at 630 nm (100 mW/cm(2) ). Resulting effects on
      bacterial viability in the biofilms were tracked by monitoring alamarBlue(r)
      conversion. Supplementary data characterizing the biofilms before and after
      exposure to PDT were acquired by Multiple Attenuated Internal Reflection Infrared
      Spectroscopy (MAIR-IR). RESULTS: The results of this study show that PDT using
      porfimer sodium and 630 nm laser light was effective in significantly reducing
      the viability of S. mutans biofilms. Maximum effectiveness was seen when biofilms
      were exposed to both photosensitizer and light versus controls. Porfimer sodium
      incubation times as short as 5 minutes in solutions as dilute as 25 ug/ml and
      illuminated with as little as 30 J/cm(2) resulted in significant decreases in
      viability of bacteria in biofilms. Optimum parameters appear to be 125 ug/ml
      porfimer sodium concentration and incubated for 5 minutes and 60 J/cm(2) of light
      energy density. CONCLUSIONS: This study has demonstrated that significant killing
      of the cariogenic organism S. mutans by the combination of a photosensitizer and
      the appropriate wavelength of laser light was possible even when the bacteria are
      embedded in an extracellular matrix.

PMID- 22847721
TI  - Infections in pediatrics: old and new diseases.
AB  - Paediatric infectious diseases have been reported since Hippocrates, and were
      always closely linked with the evolution of medicine. Current insights and
      recommendations by the Pediatric Infectious Diseases Group of Switzerland for the
      management of common paediatric diseases, such as acute otitis media,
      pharyngitis, and acute viral gastroenteritis are reviewed. The emergence of "old"
      vaccine-preventable diseases - pertussis and measles - is also discussed.
      Furthermore, the impact of the appearance of new hosts in paediatric - very low
      birthweight infants, immunosuppressed patients - is evaluated. Finally, new
      emerging paediatric infectious diseases caused by newly discovered viruses, such
      as human metapneumovirus, human bocavirus, or human coronavirus NL63 are
      explored. This overview gives a general idea on some topics that are currently
      significant and specific to paediatric infectious diseases.

PMID- 22847722
TI  - Synthetic spider silk production on a laboratory scale.
AB  - As society progresses and resources become scarcer, it is becoming increasingly
      important to cultivate new technologies that engineer next generation
      biomaterials with high performance properties. The development of these new
      structural materials must be rapid, cost-efficient and involve processing
      methodologies and products that are environmentally friendly and sustainable.
      Spiders spin a multitude of different fiber types with diverse mechanical
      properties, offering a rich source of next generation engineering materials for
      biomimicry that rival the best manmade and natural materials. Since the
      collection of large quantities of natural spider silk is impractical, synthetic
      silk production has the ability to provide scientists with access to an unlimited
      supply of threads. Therefore, if the spinning process can be streamlined and
      perfected, artificial spider fibers have the potential use for a broad range of
      applications ranging from body armor, surgical sutures, ropes and cables, tires,
      strings for musical instruments, and composites for aviation and aerospace
      technology. In order to advance the synthetic silk production process and to
      yield fibers that display low variance in their material properties from spin to
      spin, we developed a wet-spinning protocol that integrates expression of
      recombinant spider silk proteins in bacteria, purification and concentration of
      the proteins, followed by fiber extrusion and a mechanical post-spin treatment.
      This is the first visual representation that reveals a step-by-step process to
      spin and analyze artificial silk fibers on a laboratory scale. It also provides
      details to minimize the introduction of variability among fibers spun from the
      same spinning dope. Collectively, these methods will propel the process of
      artificial silk production, leading to higher quality fibers that surpass natural
      spider silks.

PMID- 22847723
TI  - Carcinosarcoma ex non-recurrent pleomorphic adenoma composed of TTF-1 positive
      large cell neuroendocrine carcinoma and myofibrosarcoma: apropos a rare Case.
AB  - We present a carcinosarcoma ex non-recurrent pleomorphic adenoma composed of a
      large cell neuroendocrine carcinomatous component and a spindle cell sarcoma with
      myofibroblastic differentiation. The tumor contained a hyalinized transition zone
      where the classical PA appeared to acquire two different histopathological
      patterns of malignant transformation of the epithelial component. The
      carcinomatous component was strongly and diffusely positive for low-molecular
      weight cytokeratins (AE1-3), synaptophysin, thyroid transcription factor-1 and
      focally positive for chromogranin A. All these markers were negative in the
      sarcomatous component. The sarcomatous component displayed immunoreactivity for
      smooth muscle actin with a predominantly linear, subplasmalemmal pattern. No
      expression of CD31, S100 protein, h-caldesmon, desmin, CD34, p63, myogenin, Myo
      D1 and c-kit was detected. Strong immunohistochemical expression of p53 was
      documented in both the carcinomatous and sarcomatous components as well as in the
      atypical epithelial component in the transition zone associated with the
      hyalinized pleomorphic adenoma.

PMID- 22847724
TI  - Association of endocrine-disrupting chemicals with total organic carbon in
      riverine water and suspended particulate matter from the Pearl River, China.
AB  - The distribution of endocrine-disrupting chemicals (EDCs) and its relationship
      with dissolved and particulate organic carbon (DOC and POC) was investigated in
      selected rivers of the Pearl River Delta, South China. The aqueous concentrations
      (average; ng/L) and particulate concentrations (average; ng/g, dry wt) for 4-tert
      octylphenol (OP), 4-nonylphenol (NP), bisphenol A (BPA), and estrone (E1) were in
      the ranges of not detectable to 153 (31.8), 276 to 2,457 (1,178), 8.4 to 628
      (161), and less than 1.5 to 11.5 (3.2), respectively, and 4.4 to 402 (98.1), 342
      to 12,053 (4,922), 12.3 to 758 (128), and not detectable to 14.4, respectively.
      The highly significant correlation of EDCs with DOC and POC, and the similar
      regression slopes, implied the critical importance of DOC and POC on the
      distribution, transport, and fate of EDCs in the aquatic environment. The in situ
      particle-water partition coefficients (log K(OC)) for OP (4.89 +/- 0.41), NP
      (5.05 +/- 0.33), and BPA (4.34 +/- 0.50) were close to those reported by other
      field studies, but one to two orders of magnitude higher than those predicted
      with n-octanol-water partition coefficient (K(OW)). The higher K(OC) values were
      attributed to the combined effects of low EDC concentrations, nonlinear sorption,
      and heterogeneity of POC and DOC. Moreover, a regression between in-situ K(OC)
      and K(OW) for phenolic xenoestrogens was observed (log K(OC) = 0.625 * log K(OW)
      + 2.28, r(2) = 0.99), suggesting that hydrophobicity contributed predominantly to
      the overall sorption of OP, NP, and BPA.

PMID- 22847725
TI  - Relative role changing of lateral collateral ligament on the posterolateral
      rotatory instability according to the knee flexion angles: a biomechanical
      comparative study of role of lateral collateral ligament and popliteofibular
      ligament.
AB  - PURPOSE: This cadaveric study assessed the relative role of the lateral
      collateral ligament (LCL) and popliteofibular ligament (PFL) in limiting tibia
      external rotation. METHODS: Eight paired cadaveric knees were divided into two
      groups. The specimens were mounted on a rotational wheel and 5 Nm external
      rotation torque was applied before and after cutting the ligaments at 0 degrees 
      30 degrees -60 degrees -90 degrees  knee flexion. Three cutting steps were
      applied: (1) PT (popliteus tendon)-, (2) LCL-, (3) PFL in group I, and (1) PT-,
      (2) PFL-, (3)LCL in group II. Increased external rotation at each step was taken
      as the ratio of final external rotation at the end of step 3. Repeated measure
      ANOVA and a Mann-Whitney U test were used for statistical analysis. RESULTS: At
      step 2, the ratio of increased external rotation after cutting the LCL (group I)
      was similar to the ratio after cutting the PFL (group II) at 0 degrees  and 30
      degrees  flexion, but that of group I was lower than group II at 60 degrees  and
      90 degrees  flexion (p = 0.029 and p = 0.029). At step-3, the ratio after cutting
      the LCL (group II) was less than the ratio after cutting the PFL (group I) at 90
      degrees  flexion (p = 0.029). CONCLUSION: The PFL and LCL play equally important
      roles in limiting external rotation at the knee extended position (0 degrees , 30
      degrees ) but the LCL contribution becomes smaller than PFL at the flexed
      position (60 degrees , 90 degrees ).

PMID- 22847726
TI  - Frameless image-guided stereotaxy with real-time visual feedback for brain
      biopsy.
AB  - BACKGROUND: Frame-based stereotaxy remains the "gold standard" for cerebral
      biopsies and functional neurosurgery though new frameless stereotactic systems
      are evolving continually. As the technique of frameless stereotaxy gains
      increasing acceptance among neurosurgeons, this study assesses the feasibility of
      a system for frameless image-guided stereotaxy. METHODS: All patients biopsied
      for intracranial lesions between February 2007 and August 2010 using the BrainLAB
      VarioGuide frameless stereotactic system were evaluated prospectively. Prior to
      surgery, patients underwent magnetic resonance (MR) imaging; additionally,
      fluoroethyl-tyrosine (FET)-positron emission tomography (PET) images were
      acquired and fused to MR images in selected cases. Biopsy trajectory length,
      lesion volume, procedure duration, and diagnostic yield were assessed. RESULTS:
      Ninety-six diagnostic biopsies in 91 patients were evaluated. Lesion volume
      ranged from 0.17 to 121.8 cm(3); trajectory length from 25.3 to 101.9 mm.
      Diagnostic yield was 93.8%. Mean operation time from skin incision to wound
      closure was 42 min; in the operating room, it was 99 min. CONCLUSIONS: Clinical
      experience indicates VarioGuide to be safe and accurate. Reachable range of
      lesion localisation appears to be comparable to a frame-based stereotaxy system.
      Operation times are brief. The unique design of this frameless stereotactic
      system allows real-time visual feedback of needle positioning.

PMID- 22847727
TI  - Predictors of community functioning in schizophrenia and substance use disorder
      patients.
AB  - Community functioning is a broad term that encompasses various 'real world'
      measures of disability among schizophrenia patients. It includes outcomes such as
      independent living, social competence and behavioural problems-all of which are
      priorities for treatment among schizophrenia patients, mental health care
      providers, and family members. An important goal for rehabilitation programs is
      to identify predictors of community functioning which, in turn, could be used as
      targets for intervention. The present case-control study examined socio
      demographic and substance use disorder (SUD) variables as well as psychiatric,
      extrapyramidal, and cognitive symptoms as predictors of community functioning in
      schizophrenia patients with (DD patients; n=31) and without comorbid SUDs (SCZ
      patients; n=31), and non-psychosis substance abusers (SUD patients; n=39).
      Psychiatric and extrapyramidal symptoms were evaluated with the Positive and
      Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia and the
      Extrapyramidal Symptoms Rating Scale. Cognition was evaluated using the Cambridge
      Neuropsychological Test Automated Battery (speed of processing, explicit and
      working memory). In SCZ patients, community functioning was predicted by explicit
      memory performance. In DD patients, community functioning was predicted by
      substance abuse, depression and speed of processing. In SUD patients, community
      functioning was predicted by substance abuse, positive symptoms and education.
      Our results suggest that cognition should be among the top treatment priorities
      in SCZ patients, whereas the key treatment targets in DD patients should be
      substance abuse and depression. Future studies will need to replicate the current
      findings, using prospective research designs.

PMID- 22847728
TI  - To anticoagulate or not to anticoagulate? That is the question : A Medline-based
      quantitative approach to share evidence on common clinical problems.

PMID- 22847729
TI  - Lung ultrasound in the diagnosis of stroke-associated pneumonia.
AB  - Pneumonia is a common complication in stroke patients; it is associated with an
      adverse outcome, prolonged hospital stay and increased health costs. The aim of
      this study was to assess the ability of lung ultrasound to rule in or rule out
      pneumonia in patients with stroke. Patients with ischemic or hemorrhagic stroke
      were included in the study if they had a clinical suspicion of pneumonia. Lung
      ultrasound imaging and chest X-ray studies were performed within 24 h from the
      onset of symptoms of pneumonia; the sonographer and radiologists were unaware of
      the chest X-ray study and ultrasound imaging results, respectively. In case of
      discordant results, lung computed tomography (CT) was performed if a definitive
      diagnosis was required to optimize clinical management. Seventy patients were
      included in the study. Among 24 patients with unilaterally positive chest X-ray
      studies, the ultrasound imaging was unilaterally positive in 19 cases (79.2 %),
      bilaterally positive in 3 cases (12.5 %) and negative in 2 cases (8.3 %). Among
      44 patients with negative chest X-ray studies, ultrasound imaging was
      unilaterally positive in 17 cases (38.6 %), bilaterally positive in 2 cases (4.6
      %), negative in 19 cases (43.2 %) and non-conclusive in 6 cases (13.6 %). A lung
      CT scan was performed in 9 of the 21 discordant cases, and it always confirmed
      the ultrasound imaging results. Ultrasound imaging and chest X-ray studies were
      concordant in 42 out of 63 cases, 66.7 % (Pearson chi(2) = 11.97, p = 0.001). In
      conclusions, this study shows the utility of LUS imaging to rule in or rule out
      pneumonia in patients with stroke. We believe that lung ultrasound imaging can
      help clinicians in the diagnosis of stroke-associated pneumonia.

PMID- 22847730
TI  - Septal course of left anterior descending artery from the right aortic sinus in
      tetralogy of Fallot: a benign anomaly and important lessons learned.
AB  - The proximal course of an anomalously arising coronary artery is a decisive
      factor in the surgical approach for tetralogy of Fallot (TOF). Studies have shown
      that echocardiography provides a good anatomic definition of the ostium and
      proximal epicardial course of coronary arteries [1, 2]. This report describes a
      case of TOF with an atrioventricular canal defect whose preoperative
      echocardiography showed abnormal origin of the left anterior descending artery
      (LAD) from right aortic sinus, which was interpreted as crossing the right
      ventricular outflow tract. Perioperative inspection did not show any abnormal
      vessel crossing the outflow, and corrective surgery was performed. At the
      echocardiographic evaluation after surgery, it was noted that the abnormal LAD
      arising from right aortic sinus was taking a septal course in relation to the
      posterior aspect of the pulmonary annulus. It is important to recognize this
      anomalous course because it is benign with no surgical implications.

PMID- 22847731
TI  - Undetected aortic arch aneurysm on chest X-ray.

PMID- 22847732
TI  - Center-out radial sampling with off-resonant reconstruction for efficient and
      accurate localization of punctate and elongated paramagnetic structures.
AB  - Accurate localization of interventional devices, for example, needles and
      brachytherapy seeds, is desired for interventional procedures. MRI is usually
      considered unsuitable for this purpose, as the induced signal voids and signal
      pile-ups do not necessarily represent the exact location of the devices. Center
      out radial sampling with off-resonance reception (co-RASOR) has been shown to
      solve this problem by repositioning the signal pile-up into the geometrical
      center of the interventional devices. However, the multiple acquisitions required
      for co-RASOR resulted in a low efficiency and unsuitability for near real-time
      interventional purposes. Herein, we aim to increase the efficiency of co-RASOR by
      relying on multiple off-resonance reconstructions of a single acquisition rather
      than on multiple acquisitions. The soundness of this approach is shown by
      demonstrating the equivalence of acquisition co-RASOR and reconstruction co
      RASOR, both theoretically and experimentally. An algorithm is proposed and
      evaluated to obtain the geometric centers of the devices, while suppressing the
      background. This procedure is shown to be effective, in vitro as well as ex vivo,
      and to yield signal intensity increases in the order of 150-400% of the average
      signal, in the geometric center of a brachytherapy seed and a needle,
      respectively. The geometric accuracy of the resultant images is confirmed by
      computed tomography.

PMID- 22847734
TI  - Modeling of red blood cell life-spans in hematologically normal populations.
AB  - Despite the impact of red blood cell (RBC) Life-spans in some disease areas such
      as diabetes or anemia of chronic kidney disease, there is no consensus on how to
      quantitatively best describe the process. Several models have been proposed to
      explain the elimination process of RBCs: random destruction process, homogeneous
      life-span model, or a series of 4-transit compartment model. The aim of this work
      was to explore the different models that have been proposed in literature, and
      modifications to those. The impact of choosing the right model on future outcomes
      prediction--in the above mentioned areas--was also investigated. Both data from
      indirect (clinical data) and direct life-span measurement (biotin-labeled data)
      methods were analyzed using non-linear mixed effects models. Analysis showed
      that: (1) predictions from non-steady state data will depend on the RBC model
      chosen; (2) the transit compartment model, which considers variation in life-span
      in the RBC population, better describes RBC survival data than the random
      destruction or homogenous life-span models; and (3) the additional incorporation
      of random destruction patterns, although improving the description of the RBC
      survival data, does not appear to provide a marked improvement when describing
      clinical data.

PMID- 22847733
TI  - An integrated functional genomics approach identifies the regulatory network
      directed by brachyury (T) in chordoma.
AB  - Chordoma is a rare malignant tumour of bone, the molecular marker of which is the
      expression of the transcription factor, brachyury. Having recently demonstrated
      that silencing brachyury induces growth arrest in a chordoma cell line, we now
      seek to identify its downstream target genes. Here we use an integrated
      functional genomics approach involving shRNA-mediated brachyury knockdown, gene
      expression microarray, ChIP-seq experiments, and bioinformatics analysis to
      achieve this goal. We confirm that the T-box binding motif of human brachyury is
      identical to that found in mouse, Xenopus, and zebrafish development, and that
      brachyury acts primarily as an activator of transcription. Using human chordoma
      samples for validation purposes, we show that brachyury binds 99 direct targets
      and indirectly influences the expression of 64 other genes, thereby acting as a
      master regulator of an elaborate oncogenic transcriptional network encompassing
      diverse signalling pathways including components of the cell cycle, and
      extracellular matrix components. Given the wide repertoire of its active binding
      and the relative specific localization of brachyury to the tumour cells, we
      propose that an RNA interference-based gene therapy approach is a plausible
      therapeutic avenue worthy of investigation.

PMID- 22847735
TI  - A sequential Monte Carlo approach to derive sampling times and windows for
      population pharmacokinetic studies.
AB  - Here we present a sequential Monte Carlo approach that can be used to find
      optimal designs. Our focus is on the design of population pharmacokinetic studies
      where the derivation of sampling windows is required, along with the optimal
      sampling schedule. The search is conducted via a particle filter which traverses
      a sequence of target distributions artificially constructed via an annealed
      utility. The algorithm derives a catalog of highly efficient designs which, not
      only contain the optimal, but can also be used to derive sampling windows. We
      demonstrate our approach by designing a hypothetical population pharmacokinetic
      study, and compare our results with those obtained via a simulation method from
      the literature.

PMID- 22847737
TI  - Hydroformylation of 1-octene using low-generation Rh(I) metallodendritic
      catalysts based on a tris-2-(2-pyridyliminoethyl)amine scaffold.
AB  - The synthesis and characterization of low-generation pyridylimine Rh(I)
      metallodendrimers is described. These metallodendrimers were obtained via a
      Schiff base condensation of tris-2-(aminoethyl)amine with 2
      pyridinecarboxaldehyde to afford the tris-2-(2-pyridylimine ethyl) amine ligand
      (1). Subsequent complexation reactions with [RhCl(CO)(2)](2) and [RhCl(COD)](2)
      yielded the corresponding metal-containing dendrimers containing -RhCl(CO) and 
      Rh(COD) moieties on the periphery. These new rhodium metallodendrimers (2 and 3)
      and their precursor ligand (1) are thermally stable and have been characterized
      using (1)H NMR, (13)C NMR, (31)P NMR, FT-IR spectroscopy, elemental analysis as
      well as mass spectrometry. The Rh(I) metallodendrimers are highly active and
      chemo- and regioselective in the hydroformylation of 1-octene. Aldehydes were
      favoured at moderate to high temperatures (95  degrees C and 75  degrees C) and
      pressure (30 bars), while more iso-octenes were formed at low temperature (55 
      degrees C) and pressures (5 and 10 bars). The mononuclear analogues (5 and 6)
      also produced more aldehydes (albeit showing catalyst decomposition at 95 
      degrees C and 75  degrees C, 30 bars) and these aldehydes were mostly branched.

PMID- 22847736
TI  - The molecular evolution of the pif family proteins in various species of
      mollusks.
AB  - Various novel proteins have been identified from many kinds of mollusk shells.
      Although such matrix proteins are believed to play important roles in the calcium
      carbonate crystal formation of shells, no common proteins that interact with
      calcium carbonate or that are involved in the molecular mechanisms behind shell
      formation have been identified. Pif consists of two proteins, Pif 80 and Pif 97,
      which are encoded by a single mRNA. Pif 80 was identified as a key acidic protein
      that regulates the formation of the nacreous layer in Pinctada fucata, while Pif
      97 has von Willebrand factor type A (VWA) and chitin-binding domains. In this
      study, we identified Pif homologues from Pinctada margaritifera, Pinctada maxima,
      Pteria penguin, Mytilus galloprovincialis, and in the genome database of Lottia
      gigantea in order to compare their primary protein sequences. The VWA and chitin
      binding domains are conserved in all Pif 97 homologues, whereas the amino acid
      sequences of the Pif 80 regions differ markedly among the species. Sequence
      alignment revealed the presence of a novel significantly conserved sequence
      between the chitin-binding domain and the C-terminus of Pif 97. Further
      examination of the Pif 80 regions suggested that they share a sequence that is
      similar to the laminin G domain. These results indicate that all Pif molecules in
      bivalves and gastropods may be derived from a common ancestral gene. These
      comparisons may shed light on the correlation between molecular evolution and
      morphology in mollusk shell microstructure.

PMID- 22847738
TI  - Functionalized derivatives of 1,4-dimethylnaphthalene as precursors for
      biomedical applications: synthesis, structures, spectroscopy and photochemical
      activation in the presence of dioxygen.
AB  - Decomposition of endoperoxide containing molecules is an attractive approach for
      the delayed release of singlet oxygen under mild reaction conditions. Here we
      describe a new method for the adaptation of the corresponding decay times by
      controlling the supramolecular functional structure of the surrounding matrix in
      the immediate vicinity of embedded singlet oxygen precursors. Thus, a significant
      prolongation of the lifetime of the endoperoxide species is possible by raising
      the energy barrier of the thermal (1)O(2)-releasing step via a restriction of the
      free volume of the applied carrier material. Enabling such a prolonged
      decomposition period is crucial for potential biomedical applications of
      endoperoxide containing molecules, since sufficient time for appropriate cell
      uptake and transport to the desired target region must be available under
      physiological conditions before the tissue damaging-power of the reactive oxygen
      species formed is completely exhausted. Two novel polyaromatic systems for the
      intermediate storage and transport of endoperoxides and the controlled release of
      singlet oxygen in the context of anticancer and antibiotic activity have been
      prepared and characterized. These compounds are based on functionalized
      derivatives of the 1,4-dimethylnaphthalene family which are readily forming
      metastable endoperoxide species in the presence of dioxygen, a photosensitizer
      molecule such as methylene blue and visible light. In contrast to previously
      known systems of similar photoreactivity, the endoperoxide carrying molecules
      have been designed with optimized molecular properties in terms of potential
      chemotherapeutic applications. These include modifications of polarity to improve
      their incorporation into various biocompatible carrier materials, the
      introduction of hydrogen bonding motifs to additionally influence the
      endoperoxide decay kinetics, and the synthesis of bifunctional derivatives to
      enable synergistic effects of multiple singlet oxygen binding sites with an
      enhanced local concentration of reactive species. With these compounds, a
      promising degree of endoperoxide stability adjustment within the carrier matrix
      has been achieved (polymer films or nanoparticles), which now opens the stage for
      appropriate targeting of the corresponding pro-drugs into live cells. First
      results on cytocidal and cytostatic properties of these compounds embedded in
      ethylcellulose nanoparticles are presented. Furthermore, an efficient low-cost
      method for the photochemical production of reactive endoperoxides based on high
      power 660 nm LED excitation at room temperature and ambient conditions in ethanol
      solution is reported.

PMID- 22847739
TI  - Chiral recognition of N-phthaloyl, N-tetrachlorophthaloyl, and N-naphthaloyl
      alpha-amino acids and their esters on polysaccharide-derived chiral stationary
      phases.
AB  - Enantiomeric separations of N-phthaloyl (N-PHT), N-tetrachlorophthaloyl (N
      TCPHT), and N-naphthaloyl (N-NPHT) alpha-amino acids and their esters were
      examined on several kinds of polysaccharide-derived chiral stationary phases
      (CSPs). Resolution capability of CSPs was greater Chiralcel OF than the others
      for N-PHT and N-NPHT alpha-amino acids and their esters. In N-TCPHT alpha-amino
      acids and their esters, good enantioselectivities showed Chiralcel OG for N-TCPHT
      alpha-amino acids, Chiralpak AD for N-TCPHT alpha-amino acid methyl esters, and
      Chiralcel OD for N-TCPHT alpha-amino acid ethyl esters, respectively. From the
      results of liquid chromatography and computational chemistry, it is concluded
      that l-form is preferred and more retained with electrostatic interaction in case
      of interaction between N-PHT alpha-amino acid derivatives and Chiralcel OF, N
      TCPHT alpha-amino acid derivatives and Chiralcel OD, and N-NPHT alpha-amino acid
      derivatives and Chiracel OF. On the other hand, d-form is preferred and more
      retained with van der Waals interaction in case of interaction between N-TCPHT
      alpha-amino acid ester derivatives and Chiralcel OG and Chiralpak AD.

PMID- 22847740
TI  - Differences in activation of mouse hepcidin by dietary iron and parenterally
      administered iron dextran: compartmentalization is critical for iron sensing.
AB  - The iron regulatory hormone hepcidin responds to both oral and parenteral iron.
      Here, we hypothesized that the diverse iron trafficking routes may affect the
      dynamics and kinetics of the hepcidin activation pathway. To address this,
      C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron
      dextran and analyzed over time. After 1 week of dietary loading with carbonyl
      iron, mice exhibited significant increases in serum iron and transferrin
      saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone
      morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin
      expression reached a plateau afterward, possibly due to upregulation of
      inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron
      continued to accumulate over 9 weeks. One day following parenteral administration
      of iron dextran, mice manifested elevated serum and hepatic iron levels and
      Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6
      mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload
      with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation
      correlated with increased transferrin saturation, partial relocation of iron from
      macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the
      physiological hepcidin response is saturable and are consistent with the idea
      that hepcidin senses exclusively iron compartmentalized within circulating
      transferrin and/or hepatocytes.

PMID- 22847742
TI  - Histone H2B lysine 120 monoubiquitination is required for embryonic stem cell
      differentiation.

PMID- 22847741
TI  - Chromatin-bound NLS proteins recruit membrane vesicles and nucleoporins for
      nuclear envelope assembly via importin-alpha/beta.
AB  - The mechanism for nuclear envelope (NE) assembly is not fully understood.
      Importin-beta and the small GTPase Ran have been implicated in the spatial
      regulation of NE assembly process. Here we report that chromatin-bound NLS
      (nuclear localization sequence) proteins provide docking sites for the NE
      precursor membrane vesicles and nucleoporins via importin-alpha and -beta during
      NE assembly in Xenopus egg extracts. We show that along with the fast recruitment
      of the abundant NLS proteins such as nucleoplasmin and histones to the
      demembranated sperm chromatin in the extracts, importin-alpha binds the chromatin
      NLS proteins rapidly. Meanwhile, importin-beta binds cytoplasmic NE precursor
      membrane vesicles and nucleoporins. Through interacting with importin-alpha on
      the chromatin NLS proteins, importin-beta targets the membrane vesicles and
      nucleoporins to the chromatin surface. Once encountering Ran-GTP on the chromatin
      generated by RCC1, importin-beta preferentially binds Ran-GTP and releases the
      membrane vesicles and nucleoporins for NE assembly. NE assembly is disrupted by
      blocking the interaction between importin-alpha and NLS proteins with excess
      soluble NLS proteins or by depletion of importin-beta from the extract. Our
      findings reveal a novel molecular mechanism for NE assembly in Xenopus egg
      extracts.

PMID- 22847743
TI  - The controversial role of Sirtuins in tumorigenesis - SIRT7 joins the debate.
AB  - Sirtuins are NAD-dependent deacetylases that are conserved from yeast to mammals.
      A new report sheds light on the function of SIRT7, the least understood member of
      the Sirtuin family by identifying its locus-specific H3K18 deacetylase activity,
      and linking it to maintenance of cellular transformation in malignancies.

PMID- 22847744
TI  - Resistance to EGFR blockade in colorectal cancer: liquid biopsies and latent
      subclones.
AB  - Two recent papers identify KRAS activation as a mechanism of acquired resistance
      to EGFR blockade in colorectal cancer. In doing so, they suggest that resistance
      to single-agent EGFR blockade will be unavoidable because these alterations exist
      as latent subclones within the tumor even prior to the initiation of therapy.

PMID- 22847745
TI  - Delivery mode and the course of pre- and postpartum depression.
AB  - PURPOSE: To compare depressiveness scores, both during and after pregnancy, with
      the delivery mode (DM). METHODS: In a longitudinal, prospective study,
      standardized questionnaires for the Edinburgh Postnatal Depression Scale were
      presented to 1,100 women and used to assess the presence and severity of
      depressiveness at three time points: prenatal, from the 30th gestational week
      (Q1); 48-72 h postnatal (Q2); and 6-8 months postnatal (Q3). The patients were
      divided into four groups relative to DM: spontaneous delivery, primary cesarean
      section (CS), secondary CS, and assisted vaginal delivery. The final number of
      participating women with both delivery mode and depression information for all
      three time points was 753. RESULTS: There was a significant difference of the
      mean EPDS values between the spontaneous delivery and primary CS groups (P=0.04)
      at Q1 (5.1 vs. 6.3). None of the other comparisons was significant. Significant
      differences relative to DM were seen at Q2 (P<0.0001), but there were no
      significant differences between the patient groups at Q3 (P=0.54). CONCLUSIONS:
      DM only showed coherence with the extent of depression briefly during the
      peripartal period. A relationship was found between depressiveness during
      pregnancy and DM, with higher depressiveness scores in the group of patients
      undergoing primary CS. This should be taken into account when patients requesting
      an elective cesarean section are being counseled.

PMID- 22847746
TI  - Aberrant right subclavian artery (ARSA) in unselected population at first and
      second trimester ultrasonography.
AB  - OBJECTIVES: To evaluate the feasibility of examining aberrant right subclavian
      artery (ARSA) at first and second trimester gestation, its prevalence and
      associations in an unselected population. METHODS: Right subclavian artery (RSA)
      was prospectively evaluated in 6617 routine patients. When ARSA was detected,
      fetal echocardiography was offered and fetal karyotyping was discussed. If
      invasive testing was performed with normal karyotype, fluorescence in situ
      hybridization for 22q11.2 microdeletion and additionally, in case of nuchal
      translucency (NT) measurement above the 99(th) centile, oligo array-based
      comparative genomic hybridization, were offered. In all aneuploidies, NT and
      first trimester additional ultrasonographic (US) markers assessment (nasal bone,
      tricuspid valve, ductus venosus) were recorded. RESULTS: RSA assessment was
      feasible in 85.3% and 98% of first and second trimester examinations,
      respectively (overall feasibility 94%). There were detected 89 ARSA (1.42% of the
      feasible cases), of which 66 in the first trimester. More than 20% were
      associated to other abnormalities: 10 aneuploidies; 2 microdeletions (15q11.2 and
      22q11.2); in the euploid fetuses, 8 associated abnormalities were observed, 4 of
      which were cardiac defects. In the case of 22q11.2 microdeletion, ARSA was
      associated only with increased NT. CONCLUSION: Prenatal routine US assessment of
      the RSA is feasible by highly experienced operators in first trimester screening.
      There is an important association of ARSA detected in unselected population with
      fetal abnormalities, including aneuploidies, cardiac defects and genetic
      anomalies. In trisomy 21 fetuses, ARSA can be the only first trimester US marker
      or, when associated to increased NT, it can represent the only 'additional'
      marker.

PMID- 22847748
TI  - Mortality after hydroxyethyl starch 130/0.4 infusion: an updated meta-analysis of
      randomized trials.
AB  - BACKGROUND: Hydroxyethyl starch (HES) is in widespread clinical use for volume
      therapy with colloids. According to the most recent meta-analysis performed in
      2010, published studies are of poor quality and report too few events to reliably
      estimate the benefits or risks of administering 6% HES 130/0.4. As results from
      new trials, reporting on a large number of events became available in 2011 and
      2012, an updated meta-analysis was performed. METHODS: Randomised controlled
      trials comparing the effects of 6% HES 130/0.4 with other colloid or crystalloid
      solutions were analysed for pooled effect size on mortality in eligible studies
      published up to 20 February 2012. RESULTS: Overall, 13 studies reporting 1,131
      participants met the inclusion criteria. The weight of evidence contributed by
      the two new trials was 51.3%. The pooled relative risk (RR) for mortality
      increased to 1.14 with a 95% confidence interval (CI) of 0.89 to 1.46.
      Publication bias favoring HES 130/0.4 was present (p = 0.038). Adjustment for the
      observed publication bias increased the RR for mortality to 1.25 (CI, 0.98 to
      1.58; p = 0.069). No heterogeneity was found (I2, 0%; CI, 0% to 32%; p = 0.81).
      CONCLUSIONS: Large-scale trials should help more precisely to determine the
      effect of HES 130/0.4 on mortality. In the interim, best current evidence
      suggests a trend toward higher mortality among HES 130/0.4 recipients.

PMID- 22847747
TI  - IgE-mediated cow's milk allergy in children.
AB  - The age at which the majority of children outgrow cow's milk allergy now appears
      to be later than previously reported. Recent studies have attempted to elucidate
      factors that may help prevent cow's milk allergy, assess markers of persistence,
      and evaluate the usefulness of new diagnostic methods. Strict avoidance of cow's
      milk has been the mainstay of treatment. However, given the potential
      nutritional, social, and immunologic ramifications of cow's milk elimination from
      a child's diet, there has been a focus on reevaluating this therapeutic approach.

PMID- 22847749
TI  - Agenesis of the internal carotid artery: associated malformations including a
      high rate of aortic and cardiac malformations.
AB  - BACKGROUND: Agenesis of the internal carotid artery (ICA) is a rare congenital
      anomaly occurring in less than 0.01% of the population, often incidentally
      discovered in pediatric populations. We recognized a high incidence of additional
      congenital malformations in children with ICA agenesis. OBJECTIVE: Our study
      reports nine cases of ICA agenesis and co-existent malformations and discusses
      implications of the association. MATERIALS AND METHODS: We conducted a
      retrospective chart review of nine children evaluated at our institution with
      imaging findings of ICA agenesis. RESULTS: Seven children (78%) had congenital
      aortic or cardiac anomalies including coarctation (4), hypoplastic left heart
      (1), tetralogy of Fallot (1), and muscular ventricular septal defect (VSD) (1).
      Four children were diagnosed with an inherited disorder: Alagille syndrome (1),
      PHACE syndrome (1), VACTERL association (1), and methylenetetrahydrofolate
      reductase (MTHFR) gene variant (1). Additional congenital anomalies are also
      described. CONCLUSION: In the setting of ICA agenesis, we report a robust
      association with congenital aortic and cardiac anomalies, as well as a broad
      spectrum of additional anatomical abnormalities that can occur in the setting of
      known genetic syndromes or as isolated findings. Knowledge of the natural history
      of ICA agenesis and associated anomalies will guide optimal care for these
      children.

PMID- 22847750
TI  - Sexual attraction, sexual identity, and psychosocial wellbeing in a national
      sample of young women during emerging adulthood.
AB  - Identity-based conceptualizations of sexual orientation may not account
      adequately for variation in young women's sexuality. Sexual minorities fare worse
      in psychosocial markers of wellbeing (i.e., depressive symptoms, anxiety, self
      esteem, social support) than heterosexual youth; however, it remains unclear
      whether these health disparities exclusively affect individuals who adopt a
      sexual minority identity or if they also may be present among heterosexually
      identified youth who report same-sex attractions. We examined the relationship
      between sexual attraction, sexual identity, and psychosocial wellbeing in the
      female only subsample (weighted, n = 391) of a national sample of emerging adults
      (age 18-24). Women in this study rated on a scale from 1 (not at all) to 5
      (extremely) their degree of sexual attraction to males and females, respectively.
      From these scores, women were divided into 4 groups (low female/low male
      attraction, low female/high male attraction, high female/low male attraction, or
      high female/high male attraction). We explored the relationship between
      experiences of attraction, reported sexual identity, and psychosocial outcomes
      using ordinary least squares regression. The results indicated sexual attraction
      to be predictive of women's psychosocial wellbeing as much as or more than sexual
      identity measures. We discuss these findings in terms of the diversity found in
      young women's sexuality, and how sexual minority status may be experienced by
      this group.

PMID- 22847751
TI  - The role of peer group aggression in predicting adolescent dating violence and
      relationship quality.
AB  - Past research has shown that adolescent peer groups make a significant
      contribution to shaping behavior but less is known about the role of peer groups
      in adolescent dating relationships. This longitudinal study examined the
      contribution of aggressive peer group norms on relationship quality and dating
      violence among dating adolescents. At the beginning of the school year (T1) and 6
      months later (T2), participants (n = 1,070; M(age) = 15.45; 49 % Female) provided
      self-reports of attitudes towards aggression, and physically- and relationally
      aggressive behaviors. Peer groups were identified using a peer-nomination
      technique and aggressive behaviors and attitudes were averaged across peer
      groups. Participants with dating experience (n = 598) reported on the frequency
      of their experience with dating violence (both as a victim and perpetrator).
      Multilevel analyses indicated that peer group relational aggression at T1
      positively predicted dating abuse victimization and perpetration, and negatively
      predicted relationship quality at T2, beyond individual predictions. An
      unexpected finding was that membership in physically aggressive peer groups at T1
      was associated positively with relationship quality at T2. Results point to the
      importance of the peer group in shaping adolescent dating experiences.

PMID- 22847752
TI  - Identity profiles in lesbian, gay, and bisexual youth: the role of family
      influences.
AB  - Sexual identity development is a central task of adolescence and young adulthood
      and can be especially challenging for sexual minority youth. Recent research has
      moved from a stage model of identity development in lesbian, gay, and bisexual
      (LGB) youth to examining identity in a non-linear, multidimensional manner. In
      addition, although families have been identified as important to youth's identity
      development, limited research has examined the influence of parental responses to
      youth's disclosure of their LGB sexual orientation on LGB identity. The current
      study examined a multidimensional model of LGB identity and its links with
      parental support and rejection. One hundred and sixty-nine LGB adolescents and
      young adults (ages 14-24, 56 % male, 48 % gay, 31 % lesbian, 21 % bisexual)
      described themselves on dimensions of LGB identity and reported on parental
      rejection, sexuality-specific social support, and non-sexuality-specific social
      support. Using latent profile analysis (LPA), two profiles were identified,
      indicating that youth experience both affirmed and struggling identities. Results
      indicated that parental rejection and sexuality-specific social support from
      families were salient links to LGB identity profile classification, while non
      sexuality specific social support was unrelated. Parental rejection and sexuality
      specific social support may be important to target in interventions for families
      to foster affirmed LGB identity development in youth.

PMID- 22847754
TI  - Flexible recalibration of binary clinical prediction models.
AB  - Calibration in binary prediction models, that is, the agreement between model
      predictions and observed outcomes, is an important aspect of assessing the
      models' utility for characterizing risk in future data. A popular technique for
      assessing model calibration first proposed by D. R. Cox in 1958 involves fitting
      a logistic model incorporating an intercept and a slope coefficient for the logit
      of the estimated probability of the outcome; good calibration is evident if these
      parameters do not appreciably differ from 0 and 1, respectively. However, in
      practice, the form of miscalibration may sometimes be more complicated. In this
      article, we expand the Cox calibration model to allow for more general
      parameterizations and derive a relative measure of miscalibration between two
      competing models from this more flexible model. We present an example
      implementation using data from the US Agency for Healthcare Research and Quality.

PMID- 22847753
TI  - Mast cells in intestinal motility disorders: please also look beyond IBS....

PMID- 22847755
TI  - Detection and molecular characterization of hepatitis E virus in clinical,
      environmental and putative animal sources.
AB  - Putative animal reservoirs and environmental samples were studied to investigate
      potential routes of transmission for indigenous hepatitis E virus (HEV) infection
      in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples
      were collected from 2003 to 2011 for this study. Four swine livers (1 %) were
      positive for HEV RNA; two strains belonged to genotype 3 and the other two
      strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a
      seawater sample. HEV strains derived from swine liver, seawater and raw sewage
      samples shared 93-100 % sequence similarity with human HEV strains.

PMID- 22847756
TI  - The increase of pericyte population in human neuromuscular disorders supports
      their role in muscle regeneration in vivo.
AB  - Pericytes are periendothelial cells that have been involved in many different
      functions including a possible role as mesodermal stem/progenitor cells. In the
      present study we demonstrate that alkaline phosphatase (AP) expression is
      specific for human muscular pericytes and can be used as a marker to identify
      them in skeletal muscle biopsies. We studied the pericyte population in skeletal
      muscle biopsies from controls, myopathic and neuropathic patients. We observed a
      significant increase in the number of pericytes only in myopathies that
      correlated with the number of NCAM(+) fibres, suggesting that an active muscular
      degenerative/regenerative process is related to an increase in the pericyte
      population. AP(+) pericytes sorted from skeletal muscle samples were able to
      activate the myogenic programme and fuse with both mononucleate satellite cells
      and mature multinucleated myotubes in vitro, demonstrating that they could
      participate in muscle regeneration. In accordance, pericytes expressing the
      myogenic transcription factor MyoD were found in biopsies of myopathic biopsies.
      All these data support the hypothesis that, apart from satellite cells, pericytes
      may play an important role in muscle regeneration in adult human muscles in vivo.

PMID- 22847762
TI  - Assessing the reproducibility of dynamic contrast enhanced magnetic resonance
      imaging in a murine model of breast cancer.
AB  - Quantitative dynamic contrast enhanced magnetic resonance imaging estimates
      parameters related to tissue vascularity and volume fractions; additionally,
      semiquantitative parameters such as the initial area under the curve can be
      utilized to describe tissue behavior. The aim of this study was to establish the
      reproducibility of quantitative and semiquantitative analysis of dynamic contrast
      enhanced magnetic resonance imaging in a murine model of breast cancer. For each
      animal, a T1-weighted, gradient-echo sequence was used to acquire two sets of
      dynamic contrast enhanced magnetic resonance imaging data separated by 5 h. Data
      were acquired at both a 0.05 mm3 (128(2) , n=12) and a 0.2 mm3 (64(2), n=12)
      resolution, and analysis was performed using both the Tofts-Kety (to estimate
      Ktrans and ve) and extended Tofts-Kety (Ktrans, ve, and vp) models.
      Reproducibility analysis was performed for both the center slice and the total
      tumor volume for all parameters. For the total volume analysis, the repeatability
      index for Ktrans is 0.073 min(-1) in the standard model analysis and 0.075 min(
      1) in the extended model analysis at the 128(2) acquisition. For the 64(2)
      acquisition, the values are 0.089 and 0.063 min(-1) for the standard and extended
      models, respectively. The repeatability index for initial area under the curve
      was 0.0039 and 0.0042 mM min for the 128(2) and 64(2) acquisitions, respectively.

PMID- 22847763
TI  - How do stream organisms respond to, and influence, the concentration of titanium
      dioxide nanoparticles? A mesocosm study with algae and herbivores.
AB  - The biologically active properties of many nanomaterials, coupled with their
      rapidly expanding production and use, has generated concern that certain types of
      nanoparticles could have unintended impacts when released into natural
      ecosystems. In the present study, the authors report the results of an experiment
      in which they grew three common species of stream algae as monocultures and
      together as polycultures in the biofilms of stream mesocosms that were exposed to
      0, 0.1, or 1.0 ppm nanoparticle titanium dioxide (nTiO(2) ). The nTiO(2) did not
      alter the growth trajectory of any algal biofilm over 10+ generations. However,
      Ti accrual in biofilms not only differed among the algal species but was also
      higher in polycultures than in the average monoculture. Variation in accrual
      among species compositions was readily predicted by differences in the total
      biomass achieved by the different biofilms. When biofilms were fed to the
      herbivorous snail Physa acuta at the end of the experiment, initial
      concentrations of nTiO(2) did not alter short-term rates of herbivory. However,
      because of differences in palatability among the algae, biofilm composition
      influenced the amount of nTiO(2) that accumulated in the herbivore tissue. The
      results have important implications for understanding how efficiently nTiO(2) is
      removed from surface waters and the potential transfer of nanomaterials to higher
      trophic levels.

PMID- 22847764
TI  - Acceptorless photocatalytic dehydrogenation for alcohol decarbonylation and imine
      synthesis.
AB  - It has come to light: Renewed interest in conversions of highly oxygenated
      materials has motivated studies of the organometallic-catalyzed photocatalytic
      dehydrogenative decarbonylation of primary alcohols into alkanes, CO, and H(2).
      Methanol, ethanol, benzyl alcohol, and cyclohexanemethanol are readily
      decarbonylated. The photocatalysts are also active for amine dehydrogenation to
      give N-alkyl aldimines and H(2).

PMID- 22847765
TI  - Development of a fibrous DNA chip for cost-effective beta-thalassemia genotyping.
AB  - beta-thalassemia is one of the most common genetic disorders worldwide. Concerted
      efforts are being made to prevent the disease, as the medical and economic burden
      of thalassemia represents a major public health problem. The molecular diagnosis
      of the beta-globin mutations that cause the disease currently involves a
      combination of classic methodologies. A microarray-based assay for parallel one
      shot detection of mutations has been developed, but the assay remains too
      expensive for routine application. We developed a cost-effective plastic fiber
      based DNA chip for the fast and reliable detection of 25 types of beta
      thalassemia mutations. Assay conditions were established and genotyping was
      successfully performed on a genomic sample from a beta-thalassemia patient. Our
      data show that this beta-thalassemia genotyping chip is an advantageous platform
      for mass genotyping because of its low cost, rapid results, and reliability.

PMID- 22847766
TI  - Intraventricular meningiomas: a consecutive series of 22 patients and literature
      review.
AB  - Intraventricular meningiomas (IVMs) are rare tumors of which the majority is
      located in the lateral ventricles. Most published series on the subject includes
      only a few patients. We analyzed our series of IVMs with a special interest in
      clinical features, outcome, and complications related to surgery. Twenty-two
      patients underwent resection of IVMs from 1990 to 2010 at Oslo University
      Hospital. Surgical and medical records were retrospectively analyzed. The IVMs
      were located in the trigonum of the lateral ventricles (20/22), in the third
      ventricle (1/22), and in the fourth ventricle (1/22). The most common symptoms
      and signs were headache, vertigo, nausea/vomiting, mental disturbances, balance
      impairment, and corticospinal tract signs. Visual field deficit was present
      preoperatively in two patients. Tumors of the lateral ventricles were resected
      via a transcortical parieto-occipital approach; the tumors in the third and
      fourth ventricle via a frontal transcortical and suboccipital route,
      respectively. Complete tumor resection was achieved in all but one case.
      Histology was WHO grade I in 20/22 and grade II in 2/22. Surgical mortality was
      0%. Most symptoms and signs resolved after surgery. The most common complication
      was visual field defect: four patients developed new-onset contralateral
      homonymous quadrant anopia and one patient developed hemianopia. Symptomatic IVMs
      should be resected, and most symptoms and signs resolve after surgery. The main
      challenge is to avoid damaging the geniculucalcarine tract when resecting IVMs in
      the trigonum. Preoperative diffusion tensor imaging-based tractography to map the
      geniculocalcarine tract could be a useful adjunct in the preoperative planning
      before selecting the surgical approach.

PMID- 22847767
TI  - Impact of low-dose involved-field radiation therapy on pediatric patients with
      lymphocyte-predominant Hodgkin lymphoma treated with chemotherapy: a report from
      the Children's Oncology Group.
AB  - BACKGROUND: Treatment of pediatric lymphocyte-predominant Hodgkin lymphoma (LPHL)
      is controversial but has typically consisted of both chemotherapy and radiation.
      Radiation therapy is associated with potential late effects in children and
      adolescents. We examined the impact of radiation therapy on long-term outcome of
      patients with LPHL treated on CCG-5942, a large pediatric cooperative group study
      of Hodgkin lymphoma (HL). PROCEDURE: Eighty-two patients with LPHL were
      registered on CCG-5942. Fifty-two patients (63%) received chemotherapy alone; 29
      patients (35%) received chemotherapy followed by involved-field radiation therapy
      (IFRT). RESULTS: The median follow-up of the LPHL patients is 7.7 years; 63
      patients (77%) have >5 years of follow-up. The 5-year event-free survival (EFS)
      and overall survival (OS) were 97% and 100%. Two relapses occurred, both in
      patients who did not receive IFRT. There were no significant differences in EFS
      or OS between patients who received or did not receive IFRT. CONCLUSIONS: This
      subset analysis demonstrates the chemosensitivity of pediatric LPHL. Patients who
      had a complete response to chemotherapy had an excellent EFS and OS without the
      addition of radiotherapy.

PMID- 22847768
TI  - Thiamethoxam acts as a target-site synergist of spinosad in resistant strains of
      Frankliniella occidentalis.
AB  - BACKGROUND: Previous studies have suggested that the resistance mechanism towards
      spinosad in Frankliniella occidentalis (Pergande) is an altered target site. Like
      the neonicotinoids, the spinosyns act on nicotinic acetylcholine receptors
      (nAChRs) in insects, but at a distinct site. The changes in nAChRs related to
      spinosad resistance in thrips might involve interaction with neonicotinoids. In
      this study, the efficacy of spinosad and neonicotinoids, alone and in
      combination, was evaluated in susceptible and spinosad-resistant thrips strains.
      RESULTS: The neonicotinoids tested were imidacloprid, thiacloprid, acetamiprid,
      thiamethoxam and clothianidin. No cross-resistance was shown between spinosad and
      any of the neonicotinoids. However, an increased toxicity was observed when a
      mixture of spinosad with thiamethoxam or clothianidin was tested. No synergism
      was found in the susceptible strains. The more spinosad-resistant the thrips
      strain, the stronger was the synergism. CONCLUSION: Data suggest that spinosad
      and thiamethoxam may interact at the nAChRs in spinosad-resistant thrips,
      facilitating enhanced insecticidal action.

PMID- 22847769
TI  - Endoplasmic reticulum stress in cardiometabolic disorders.
AB  - When endoplasmic reticulum (ER) homeostasis is disrupted, an adaptive signaling
      pathway, called the unfolded protein response (UPR) is activated to help ER cope
      with the stress. The UPR is an important signal transduction pathway, crucial for
      the survival and function of all cells. Recently, there has been a substantial
      progress made in understanding the molecular mechanisms of physiological UPR
      regulation and its role in the pathogenesis of many diseases including metabolic
      diseases. Studies using mouse models lacking or overexpressing the factors
      involved in ER stress signaling as well as work performed on humans have revealed
      the contribution of UPR to disease progression. This review focuses on the
      regulation of UPR signaling and its relevance in pathogenesis of metabolic
      diseases.

PMID- 22847770
TI  - The plaque "micro" environment: microRNAs control the risk and the development of
      atherosclerosis.
AB  - While the discovery of microRNAs has exponentially expanded our understanding of
      the regulatory mechanisms governing gene networks in many biological processes,
      the study of these tiny RNA powerhouses in cardiovascular disease is in its
      infancy. To date, there have been over 1200 human microRNAs identified, and they
      are estimated to affect the expression of over half of the protein-coding portion
      of the human genome. In this review, we will discuss miRNAs that are integral
      players in processes affecting risk factors for CVD, as well as miRNAs that act
      at the level of the vessel wall to affect atherogenesis. We will discuss how
      microRNAs are not only advancing the field of cardiovascular biology, but how
      some miRNAs are at the forefront of drug development and may be soon advancing
      into the clinic.

PMID- 22847771
TI  - Cardiac stem cells in patients with ischemic cardiomyopathy: discovery,
      translation, and clinical investigation.
AB  - The increasing prevalence of heart failure, in the US and worldwide, poses a
      significant burden to patients, practitioners, and healthcare systems. Hence,
      there is a pressing need for alternative therapies to enhance the current
      treatment armamentarium. Accordingly, when considering heart failure of ischemic
      etiology, an intervention designed to regenerate the attending loss of myocardium
      could potentially result in improved cardiac function, functional status, and
      quality of life. Significant strides have been made by investigators in the study
      of stem cell therapy for cardiac repair; recently with cardiac-derived progenitor
      cells. These cells include cardiospheres, cardiosphere-derived cells, and c-kit
      positive cardiac stem cells. Herein, a review of both preclinical studies and
      phase I clinical trials of these cell types is presented. A detailed account of
      in vitro characterization, in vivo bioactivity, and safety and efficacy in humans
      is outlined. Thus far, encouraging results have been realized, although larger
      studies have yet to be undertaken.

PMID- 22847773
TI  - Dietary carbohydrates for diabetics.
AB  - The literature on the impact of dietary carbohydrates in the regulation of blood
      glucose levels and other metabolic abnormalities in diabetic patients over the
      last 3 years is reviewed. We try to differentiate the metabolic effects due to
      the amount of carbohydrates from those due to their different types. The review
      comprises a part dealing with the effects of diets having low or high
      carbohydrate content on body weight reduction, and a part in which the amount and
      the quality of carbohydrates are discussed in relation to isoenergetic diets.
      Overall, the data accumulated in the period considered seem to confirm that the
      decrease in energy intake is more important than the qualitative composition of
      the diet to reduce body weight, but that both the amount and the quality of
      carbohydrates are important in modulating blood glucose levels and other
      cardiovascular risk factors in both the fasting and the postprandial phases in
      diabetic individuals.

PMID- 22847772
TI  - Making a difference: monocyte heterogeneity in cardiovascular disease.
AB  - Monocytes are frequently described as bone marrow-derived precursors of
      macrophages. Although many studies support this view, we now appreciate that
      monocytes neither develop exclusively in the bone marrow nor give rise to all
      macrophages and dendritic cells. In addition to differentiating to specific
      leukocyte populations, monocytes, as monocytes, are functionally and
      ontogenically heterogeneous. In this review we will focus on the development and
      activity of monocytes and their subsets in mice (Ly-6 C(high/low)) and humans
      (CD14(+/dim/-) CD16(+/-)) in the context of atherosclerosis and its
      complications.

PMID- 22847774
TI  - Evaluation of nasal airways by objective methods in chronic otitis media.
AB  - Otitis media (OM) is a common health problem. Nasal airways play an important
      role in etiopathogenesis of OM. The aim of this study is to evaluate nasal
      airways by objective methods in chronic otitis media (COM) cases. The
      relationship between the course of the disease and nasal parameters is also
      investigated. Fifty-six patients who had chosen an operation for chronic otitis
      media were included in the study. The control group was composed of 30 healthy
      patients. Patients were subjected to acoustic rhinometry and rhinomanometry.
      Nasal airway resistance and cross-sectional area measurements were taken. The
      results of the COM group and the control group were compared. Cases were
      classified by the course of the disease such as suppurative/progressive/active
      and non-suppurative/inactive and the nasal parameters of these sub-groups were
      compared. In cases with unilateral COM, nasal cavity results from both sides were
      compared. The nasal airway resistance of the COM group was statistically
      significantly higher than the control group (p < 0.05). However, there was no
      difference in cross-sectional area measurements. There was no significant
      difference between the suppurative/progressive/active and non
      suppurative/inactive groups. However, the suppurative group had higher nasal
      resistance (p > 0.05). There was no statistical difference between the
      measurements of each side in unilateral COM cases. This study found that COM
      cases have greater nasal airway resistance. No significant difference was found
      in cross-sectional area measurements so the increase in resistance may be linked
      to mucosal rather than structural changes. There was no evidence for a
      relationship between the course of the OM and nasal airway parameters.

PMID- 22847776
TI  - Two independent de novo mutations as a cause for neurofibromatosis type 1 and
      Noonan syndrome in a single family.
AB  - Here we report on a family with two siblings born to unrelated healthy parents,
      one with neurofibromatosis type 1 (NF1) and the other with Noonan syndrome (NS).
      Molecular investigations performed on the NF1 and PTPN11 genes showed two
      independent de novo mutations as a cause for NF1 in the NF1 proband and NS in her
      affected brother. Both de novo mutations were potentially of paternal origin,
      given the advanced paternal age at the time of conception.

PMID- 22847775
TI  - Assaying the proton transport and regulation of UCP1 using solid supported
      membranes.
AB  - The uncoupling protein 1 (UCP1) is a mitochondrial protein that carries protons
      across the inner mitochondrial membrane. It has an important role in non
      shivering thermogenesis, and recent evidence suggests its role in human adult
      metabolism. Using rapid solution exchange on solid supported membranes, we
      succeeded in measuring electrical currents generated by the transport activity of
      UCP1. The protein was purified from mouse brown adipose tissue, reconstituted in
      liposomes and absorbed on solid supported membranes. A fast pH jump activated the
      ion transport, and electrical signals could be recorded. The currents were
      characterized by a fast rise and a slow decay, were stable over time, inhibited
      by purine nucleotides and activated by fatty acids. This new assay permits direct
      observation of UCP1 activity in controlled cell-free conditions, and opens up new
      possibilities for UCP1 functional characterization and drug screening because of
      its robustness and its potential for automation.

PMID- 22847777
TI  - Should clinical studies guide clinical practice?

PMID- 22847778
TI  - Detection rates of clinically significant genomic alterations by microarray
      analysis for specific anomalies detected by ultrasound.
AB  - OBJECTIVE: The aim of this study is to understand the diagnostic utility of
      comparative genomic hybridization (CGH)-based microarrays for pregnancies with
      abnormal ultrasound findings. METHODS: We performed a retrospective analysis of
      2858 pregnancies with abnormal ultrasounds and normal karyotypes (when performed)
      tested in our laboratory using CGH microarrays targeted to known chromosomal
      syndromes with later versions providing backbone coverage of the entire genome.
      Abnormalities were stratified according to organ system involvement. Detection
      rates for clinically significant findings among these categories were calculated.
      RESULTS: Clinically significant genomic alterations were identified in cases with
      a single ultrasound anomaly (n = 99/1773, 5.6%), anomalies in two or more organ
      systems (n = 77/808, 9.5%), isolated growth abnormalities (n = 2/76, 2.6%), and
      soft markers (n = 2/77, 2.6%). The following anomalies in isolation or with
      additional anomalies had particularly high detection rates: holoprosencephaly (n
      = 9/85, 10.6%), posterior fossa defects (n = 21/144, 14.6%), skeletal anomalies
      (n = 15/140, 10.7%), ventricular septal defect (n = 14/132, 10.6%), hypoplastic
      left heart (n = 11/68, 16.2%), and cleft lip/palate (n = 14/136, 10.3%).
      CONCLUSIONS: Microarray analysis identified clinically significant genomic
      alterations in 6.5% of cases with one or more abnormal ultrasound findings; the
      majority were below the resolution of karyotyping. Larger data sets such as this
      allow for sub-stratification by specific anomalies to determine risks for genomic
      alterations detectable by microarray analysis.

PMID- 22847779
TI  - Mechanical and biological performances of new scaffolds made of collagen
      hydrogels and fibroin microfibers for vascular tissue engineering.
AB  - A microstructured composite material made of collagen hydrogel (matrix) and silk
      fibroin microfibers (randomly oriented reinforcing fibers) is investigated in
      order to conjugate the mechanical resistance of fibroin with the suitable
      biological performance of collagen to design new scaffolds for vascular tissue
      engineering. Results show that fibroin microfibers and collagen fibrils have
      suitable interfacial adhesion, and the scaffold exhibits improved mechanical
      properties if compared with a pure collagen hydrogel. Furthermore, the overall
      biological performance is improved.

PMID- 22847780
TI  - Dietary L-leucine and L-alanine supplementation have similar acute effects in the
      prevention of high-fat diet-induced obesity.
AB  - High-protein diets have been shown to alleviate detrimental effects of high-fat
      diets and this effect can be partially mimicked by dietary L-leucine
      supplementation. Here, we aimed to elucidate the early mechanisms and the
      specificity of leucine effects. We performed a 1-week trial with male C57BL/6
      mice fed ad libitum with semisynthetic high-fat diets containing an adequate (10
      % w/w, AP) or high (50 % w/w, HP) amount of whey protein, or supplemented with L
      leucine corresponding to the leucine content within the HP diet (Leu) or
      supplemented with equimolar L-alanine (Ala). Food and water intake were monitored
      continuously using a computer-controlled monitor system and body composition
      changes were assessed using quantitative NMR. HP completely prevented the AP
      induced accumulation of body fat. Leu and Ala resulted in a similar reduction of
      body fat accumulation which was intermediate between AP and HP. There were no
      significant effects on plasma glucose or insulin. Triacylglycerol content and
      gene expression of lipogenesis enzymes in liver as well as plasma cholesterol
      were reduced by HP compared to AP with Leu and Ala again showing intermediate
      effects. Body fat gain and liver triacylglycerols were strongly correlated with
      total energy intake. Water intake was rapidly increased by HP feeding and total
      water intake correlated strongly with total amino nitrogen intake. We concluded
      that the positive effects of high-protein diets on metabolic syndrome associated
      traits are acutely due to effects on satiety possibly linked to amino nitrogen
      intake and on the subsequent suppression of liver lipogenesis without evidence
      for a specific leucine effect.

PMID- 22847781
TI  - In memoriam: John E. Folk (1925-2010).

PMID- 22847782
TI  - Serine racemase: an unconventional enzyme for an unconventional transmitter.
AB  - The discovery of large amounts of D-serine in the brain challenged the dogma that
      only L-amino acids are relevant for eukaryotes. The levels of D-serine in the
      brain are higher than many L-amino acids and account for as much as one-third of
      L-serine levels. Several studies in the last decades have demonstrated a role of
      D-serine as an endogenous agonist of N-methyl-D-aspartate receptors (NMDARs). D
      Serine is required for NMDAR activity during normal neurotransmission as well as
      NMDAR overactivation that takes place in neurodegenerative conditions. Still,
      there are many unanswered questions about D-serine neurobiology, including
      regulation of its synthesis, release and metabolism. Here, we review the
      mechanisms of D-serine synthesis by serine racemase and discuss the lessons we
      can learn from serine racemase knockout mice, focusing on the roles attributed to
      D-serine and its cellular origin.

PMID- 22847783
TI  - Do dynamic-based MR knee kinematics methods produce the same results as static
      methods?
AB  - MR-based methods provide low risk, noninvasive assessment of joint kinematics;
      however, these methods often use static positions or require many identical
      cycles of movement. The study objective was to compare the 3D kinematic results
      approximated from a series of sequential static poses of the knee with the 3D
      kinematic results obtained from continuous dynamic movement of the knee. To
      accomplish this objective, we compared kinematic data from a validated static MR
      method to a fast static MR method, and compared kinematic data from both static
      methods to a newly developed dynamic MR method. Ten normal volunteers were imaged
      using the three kinematic methods (dynamic, static standard, and static fast).
      Results showed that the two sets of static results were in agreement, indicating
      that the sequences (standard and fast) may be used interchangeably. Dynamic
      kinematic results were significantly different from both static results in eight
      of 11 kinematic parameters: patellar flexion, patellar tilt, patellar proximal
      translation, patellar lateral translation, patellar anterior translation, tibial
      abduction, tibial internal rotation, and tibial anterior translation. Three
      dimensional MR kinematics measured from dynamic knee motion are often different
      from those measured in a static knee at several positions, indicating that
      dynamic-based kinematics provides information that is not obtainable from static
      scans.

PMID- 22847784
TI  - GEF-H1 over-expression in hepatocellular carcinoma promotes cell motility via
      activation of RhoA signalling.
AB  - The interstitial chromosome (chr.) 1q21-q22 region is frequently amplified in
      human cancers, where it has been reported to carry prognostic significance for
      patients. We attempted to delineate chr. 1q21-q22 for affected gene(s) in
      hepatocellular carcinoma (HCC) by array-CGH and detected copy number gains of rho
      guanine nucleotide exchange factor-H1 (GEF-H1) as most significant event. Gene
      expression evaluation in the HCC cohort indicated common up-regulations of GEF-H1
      in 64% tumours compared to adjacent non-tumoural liver (64/100; paired t-test p <
      0.0001). Moreover, GEF-H1 over-expressions correlated with microvascular invasion
      and advanced-stage tumours (p < 0.05). High GEF-H1 levels also predict shorter
      disease-free and overall survival of HCC patients (p < 0.03). Functional knock
      down of GEF-H1 by RNAi indicated marked reduction in cell invasion through
      matrigel and an inhibition of cell migration (p < 0.035), but an effect on cell
      viability was not apparent. More interestingly, a mesenchymal-epithelial
      transition (MET) was readily observed in GEF-H1 knock-down cells, where a
      concomitant re-expression of epithelial markers (E-cadherin and cytokeratin 18)
      and cell adhesion proteins (alpha-catenin and gamma-catenin) was found but down
      regulation of mesenchymal features (N-cadherin, vimentin and fibronectin). This
      phenotype was accompanied by reduced filamentous actin polymerizations and
      diminution of the stress fibre formation. In addition, reduced active form of GTP
      RhoA, together with its downstream effectors, including cleaved ROCK1 and
      phosphorylated MLC2, were also detected in GEF-H1-depleted cells. Taken together,
      our findings underscore a potent oncogenic role for GEF-H1 in promoting the
      metastatic potentials of HCC, possibly through activation of RhoA signalling and
      the EMT phenomenon.

PMID- 22847787
TI  - Gold-catalyzed synthesis of furans and furanones from sulfur ylides.

PMID- 22847785
TI  - A phase I study of prolonged infusion of triapine in combination with fixed dose
      rate gemcitabine in patients with advanced solid tumors.
AB  - PURPOSE: Prolonged exposure of cancer cells to triapine, an inhibitor of
      ribonucleotide reductase, followed by gemcitabine enhances gemcitabine activity
      in vitro. Fixed-dose-rate gemcitabine (FDR-G) has improved efficacy compared to
      standard-dose. We conducted a phase I trial to determine the maximum tolerated
      dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary
      efficacy of prolonged triapine infusion followed by FDR-G. EXPERIMENTAL DESIGN:
      Triapine was given as a 24-hour infusion, immediately followed by FDR-G (1000
      mg/m(2) over 100-minute). Initially, this combination was administered days 1 and
      8 of a 21-day cycle (Arm A, triapine starting dose 120 mg); but because of
      myelosuppression, it was changed to days 1 and 15 of a 28-day cycle (Arm B,
      starting dose of triapine 75 mg). Triapine steady-state concentrations (Css) and
      circulating ribonucleotide reductase M2-subunit (RRM2) were measured. RESULTS:
      Thirty-six patients were enrolled. The MTD was determined to be triapine 90 mg
      (24-hour infusion) immediately followed by gemcitabine 1000 mg/m(2) (100-minute
      infusion), every 2 weeks of a 4-week cycle. DLTs included grade 4
      thrombocytopenia, leukopenia and neutropenia. The treatment was well tolerated
      with fatigue, nausea/vomiting, fever, transaminitis, and cytopenias being the
      most common toxicities. Among 30 evaluable patients, 1 had a partial response and
      15 had stable disease. Triapine PK was similar, although more variable, compared
      to previous studies using doses normalized to body-surface-area. Steady decline
      in circulating levels of RRM2 may correlate with outcome. CONCLUSIONS: This
      combination was well tolerated and showed evidence of preliminary activity in
      this heavily pretreated patient population, including prior gemcitabine failure.

PMID- 22847786
TI  - Pre-operative chemoradiation followed by post-operative adjuvant therapy with
      tetrathiomolybdate, a novel copper chelator, for patients with resectable
      esophageal cancer.
AB  - Introduction This phase II trial investigated chemoradiation followed by surgery
      and 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer.
      Methods Patients with resectable, locally advanced esophageal cancer received
      neoadjuvant cisplatin 60 mg/m(2) (days 1 and 22), paclitaxel 60 mg/m(2) (days 1,
      8, 15, and 22), and 45 Gy hyperfractionated radiotherapy for 3 weeks followed by
      transhiatal esophagectomy. TM 20 mg PO QD was started 4 weeks post-op, and
      continued for 2 years to maintain the ceruloplasmin level between 5 and 15 mg/dl.
      Results Sixty-nine patients were enrolled (median age, 60 years). Sixty-six
      patients underwent surgery and 61 patients had a complete resection. Histologic
      complete response rate was 10 %. Twenty-one patients did not receive TM
      (metastases noted in the peri-operative period, prolonged post-operative recovery
      time, or patient refusal). Forty-eight patients started TM; 14 completed 24
      months of treatment, 11 completed 10-18 months, 15 completed 2-8 months, and 8
      completed <=1 month. Twenty-seven patients had disease recurrence. With a median
      follow-up of 55 months, 25 patients were alive without disease, 1 was alive with
      disease, and 43 have died. Three-year recurrence-free survival was 44 % (95 % CI,
      32-55 %) and the three-year overall survival was 45 % (95 % CI 33-56 %).
      Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant
      setting. Disease-free survival and overall survival are promising when compared
      to historical controls treated at our institution with a similar regimen that did
      not include TM. However, the challenges associated with prolonged administration
      limit further investigation.

PMID- 22847788
TI  - Biomagnification of polychlorinated biphenyls in a harbor seal (Phoca vitulina)
      food web from the Strait of Georgia, British Columbia, Canada.
AB  - Polychlorinated biphenyl (PCB) biomagnification was characterized in a harbor
      seal food web in the Strait of Georgia, British Columbia, Canada. Trophic
      magnification factors (TMFs) for PCBs averaged 3.6, with a range of 0.7 to 9.4.
      The TMFs for individual congeners correlated with log K(OW) (r(2) = 0.56, p <
      0.001), reflecting the role that physicochemical properties play in driving the
      biomagnification of PCBs in marine food webs. However, TMFs differed among PCB
      structure activity groups, clearly indicating an additional role for metabolic
      transformation of certain PCBs. The known feeding preferences of harbor seals
      enabled the calculation of trophic level-adjusted biomagnification factors
      (BMF(TL)) for PCBs in this species, which averaged 13.4 and ranged from 0.2 to
      150.6. Metabolic transformation in seals explained some of the variation in
      congener-specific biomagnification, with lower BMF(TL) values for PCB congeners
      with meta- and parachlorine unsubstituted positions. Principal components
      analysis revealed the distinct roles played by trophic level, log K(OW), and
      metabolic transformation in explaining the notable differences in PCB patterns
      among harbor seals, their pups, and their prey. In the present study, the authors
      estimate there to be approximately 76 kg of PCBs in the biota of the Strait of
      Georgia, of which 1.6 kg is retained by harbor seals.

PMID- 22847789
TI  - A revision of sexual mixing matrices in models of sexually transmitted infection.
AB  - Two sexual mixing matrices previously used in models of sexually transmitted
      infections (STIs) are intended to calculate the probability of sexual interaction
      between age groups and sexual behaviour subgroups. When these matrices are used
      to specify multiple criteria for how people select sexual partners (such as age
      group and sexual behaviour class), their conditional probability structure means
      that they have in practice been prone to misuse. We constructed revised mixing
      matrices that incorporate a corrected conditional probability structure and then
      used one of them to examine the effect of this revision on population modelling
      of STIs. Using a dynamic model of human papillomavirus (HPV) transmission as an
      example, we examined changes to estimates of HPV prevalence and the relative
      reduction in age-standardised HPV incidence after the commencement of publicly
      funded HPV vaccination in Australia. When all other model specifications were
      left unchanged, the revised mixing matrix initially led to estimates of age
      specific oncogenic HPV prevalence that were up to 11% higher than our previous
      models at certain ages. After re-calibrating the model by modifying unobservable
      parameters characterising HPV natural history, the revised mixing matrix yielded
      similar estimates to our previous models, predicting that vaccination would lead
      to relative HPV incidence reductions of 43% and 85% by 2010 and 2050,
      respectively, compared with 43% and 86% using the unrevised mixing matrix
      formulation. Our revised mixing matrix offers a rigorous alternative to commonly
      used mixing matrices, which can be used to reliably and explicitly accommodate
      conditional probabilities, with appropriate re-calibration of unobservable model
      parameters.

PMID- 22847790
TI  - Outcomes of immunological interventions for mixed chimerism following allogeneic
      stem cell transplantation in children with juvenile myelomonocytic leukemia.
AB  - BACKGROUND: For children with juvenile myelomonocytic leukemia (JMML) who undergo
      stem cell transplantation (SCT), the role of immunological interventions
      including withdrawal of immunosuppressive therapy (IST) and donor lymphocyte
      infusion (DLI) for treatment of disease recurrence remains uncertain. PROCEDURE:
      We analyzed serial chimerism status following SCT and evaluated the efficacy of
      immunological interventions for the management of mixed chimerism (MC) in
      children with JMML. RESULTS: Chimerism analysis was available in 26 SCT cases
      following the first and second SCT. MC was observed in 16 cases and withdrawal of
      IST was performed in 14 cases immediately after identification of MC. Donor
      lymphocyte infusion (DLI) was performed in five MC cases. Eight MC cases were
      observed at the time of neutrophil recovery. Following withdrawal of IST, three
      cases achieved complete chimerism (CC) while the proportion of autologous cells
      increased rapidly in the remaining five cases. Six MC cases were observed after
      achievement of hematological remission (HR) and responses to withdrawal of IST
      were observed in two cases. In the remaining four cases, despite withdrawal of
      IST, the proportion of autologous cells increased. Five cases received DLI but
      only one case responded. CONCLUSION: Although the benefits of immunological
      interventions for MC after SCT in JMML were limited, some patients did achieve HR
      as a result of these treatment modalities without a second SCT. Close monitoring
      of donor chimerism and early detection of MC is helpful in guiding treatment
      after SCT in children with JMML.

PMID- 22847791
TI  - Local electronic properties of corrugated silicene phases.

PMID- 22847799
TI  - Are all readmissions the same?

PMID- 22847800
TI  - Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl
      epitope-activated immune responders: findings from a pilot study.
AB  - BACKGROUND: Dendritic cell (DC)-based and cytokine-induced killer cell (CIK)
      based therapy can induce specific antitumor T-cell responses. This clinical pilot
      study examined the safety, the feasibility, and the outcome of tumor-specific
      immunotherapy for patients with advanced pancreatic adenocarcinoma. METHODS:
      Alpha-Gal epitopes were synthesised on pancreatic carcinoma cell membranes with
      alpha1,3-galactosyltransferase in vitro. Subsequently, the addition of natural
      human anti-Gal IgG to the processed membranes resulted in opsonization and
      effective phagocytosis by DCs, which were co-cultured with newly differentiated
      CIKs from bone marrow stem cells to generate tumor-specific immune responders ex
      vivo. Fourteen patients with inoperable stage III/IV pancreatic adenocarcinoma
      were enrolled in the study; the treatment procedure consisted of injections of
      DCs and CIKs. RESULTS: Clinical observation showed that the procedure was safe
      and lacked serious side effects. Tests showed that 12 patients had strong
      positive delayed-type IV hypersensitivity to the autologous cancer cell lysate;
      robust systemic cytotoxicity elicited by interferon (IFN)gamma expression by
      peripheral blood mononuclear cells; and significant increases in CD3+CD8+,
      CD3+CD45RO+, and CD3+CD56+ cells in peripheral blood lymphocytes after 3
      injections. During the follow up, the percentages of CD3+CD8+, CD3+CD45RO+, and
      CD3+CD56+ cells returned to the normal range at 6 to 9 months after the third
      injection and IFNgamma expression in the cells stayed at the higher level from
      the third injection to 24 months after the treatment. CONCLUSIONS: This new tumor
      specific immunotherapy is safe, feasible, and has great potential for pancreatic
      carcinoma treatment.

PMID- 22847801
TI  - The role of sequential chemoradiation for local advanced oropharyngeal carcinoma.
AB  - BACKGROUND: This study aims to assess survival, prognostic indicators, and
      pattern of failure for advanced oropharyngeal cancer treated by induction
      chemotherapy followed by concomitant chemoradiation (sequential CRT). METHODS: A
      retrospective review of 80 consecutive patients who underwent chemoradiation
      [doublet cisplatin and 5-fluorouracil (PF)] for local advanced oropharyngeal
      carcinoma at a tertiary center from March 2003 to July 2008 is reported. Seven
      studies utilizing a similar protocol were reviewed, and all outcomes are
      collated. RESULT: At a median follow-up of 32 months, the 3-year overall survival
      was 75%. Tumor size (p < 0.001), age at presentation (p < 0.002), and failure to
      complete the full course of induction chemotherapy (p < 0.01) were all found to
      be significant factors affecting survival. CONCLUSION: Induction chemotherapy
      followed by concomitant chemoradiation utilizing doublet PF is an effective
      treatment for local advanced oropharyngeal carcinoma. At present, the addition of
      a taxane to the PF regimen cannot be assumed to provide benefit until further
      evidence emerges from a representative controlled trial.

PMID- 22847802
TI  - Mechanical and kinetic properties of beta-cardiac/slow skeletal muscle myosin.
AB  - We aimed to establish reference parameters to identify functional effects of
      familial hypertrophic cardiomyopathy-related point mutations in the beta
      cardiac/slow skeletal muscle myosin heavy chain (beta-cardiac/MyHC-1). We
      determined mechanical and kinetic parameters of the beta-cardiac/MyHC-1 using
      human soleus muscle fibers that express the same myosin heavy chain (MyHC-1) as
      ventricular myocardium (beta-cardiac). The observed parameters are compared to
      previously reported data for rabbit psoas muscle fibers. We found all of the
      examined kinetic parameters to be slower in soleus fibers than in rabbit psoas
      muscle. Somewhat surprisingly, however, we also found that the stiffness of the
      beta-cardiac/MyHC-1 head domain is more than 3-fold lower than the stiffness of
      the fast isoform of psoas fibers. Furthermore, and different from rabbit psoas
      muscle, in human soleus fibers both the occupancy of force-generating cross
      bridge states as well as the elastic extension of force-generating heads increase
      with temperature. Thus, a myosin head in the force generating states makes an
      increasing contribution to force with temperature. We support some of our fiber
      data by data from in vitro motility and optical trapping assays. Initial findings
      with FHC-related point mutations in the converter imply that the differences in
      stiffness of the head domain between the slow and fast isoform may well be due to
      particular differences in the amino acid sequence of the converter. We show that
      the slower kinetics may be linked to a larger flexibility of the beta
      cardiac/MyHC-1 isoform compared to fast MyHC isoforms.

PMID- 22847805
TI  - Motion correspondence in the Ternus display shows feature bias in spatiotopic
      coordinates.
AB  - How is the visual system able to maintain object identity as the objects or the
      eyes move? While many early studies have shown small or no influence of feature
      information on this correspondence process, more recent studies have shown large
      feature effects. Here we investigated if this incongruity might be due to the
      distance over which the feature influence has an effect. We used a variation of
      the Ternus display (Ternus, 1926), an ambiguous apparent motion display, in which
      two sets of three discs are presented and one can perceive either three discs
      moving together (group motion) or one disc jumping across the other two discs
      (element motion). We biased the percept toward element motion by matching the
      features of some of the discs. In Experiment 1, with the three discs aligned and
      moving vertically, we added a horizontal offset between the two sets of discs and
      found a strong bias toward element motion that decreased with increasing spatial
      offset. In Experiment 3 participants had to make horizontal saccades across the
      same Ternus displays so that the two Ternus frames were horizontally offset on
      the retina, but not in spatiotopic coordinates. We found that the bias showed a
      similar spatial range, but now it was clear that the range was set in spatial
      coordinates independently of the retinal position. These results show that
      feature information contributes to correspondence over a limited spatial range
      (Experiment 1) and that the range is imposed in spatial, not retinal, coordinates
      (Experiment 2).

PMID- 22847803
TI  - Inhibition of GSK3 abolishes bacterial-induced periodontal bone loss in mice.
AB  - The tissue destruction that characterizes periodontitis is driven by the host
      response to bacterial pathogens. Inhibition of glycogen synthase kinase 3beta
      (GSK3beta) in innate cells leads to suppression of Toll-like receptor (TLR)
      initiated proinflammatory cytokines under nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) p65 transcriptional control and
      promotion of cyclic adenosine monophosphate response element-binding (CREB)
      dependent gene activation. Therefore, we hypothesized that the cell permeable
      GSK3-specific inhibitor, SB216763, would protect against alveolar bone loss
      induced by the key periodontal pathogen, Porphyromonas gingivalis (P.
      gingivalis), in a murine model. B6129SF2/J mice either were infected orally with
      P. gingivalis ATCC 33277; or treated with SB216763 and infected with P.
      gingivalis; sham infected; or exposed to vehicle only (dimethyl sulfoxide
      [DMSO]); or to GSK3 inhibitor only (SB216763). Alveolar bone loss and local
      (neutrophil infiltration and interleukin [IL]-17) and systemic (tumor necrosis
      factor [TNF], IL-6, Il-1beta and IL-12/IL-23 p40) inflammatory indices also were
      monitored. SB216763 unequivocally abrogated mean P. gingivalis-induced bone
      resorption, measured at 14 predetermined points on the molars of defleshed
      maxillae as the distance from the cementoenamel junction to the alveolar bone
      crest (p < 0.05). The systemic cytokine response, the local neutrophil
      infiltration and the IL-17 expression were suppressed (p < 0.001). These data
      confirm the relevance of prior in vitro phenomena and establish GSK3 as a novel,
      efficacious therapeutic preventing periodontal disease progression in a
      susceptible host. These findings also may have relevance to other chronic
      inflammatory diseases and the systemic sequelae associated with periodontal
      infections.

PMID- 22847806
TI  - Recognizing identity in the face of change: the development of an expression
      independent representation of facial identity.
AB  - Perceptual aftereffects have indicated that there is an asymmetry in the extent
      to which adults' representations of identity and expression are independent of
      one another. Their representation of expression is identity-dependent; the
      magnitude of expression aftereffects is reduced when the adaptation and test
      stimuli have different identities. In contrast, their representation of identity
      is expression-independent; the magnitude of identity aftereffects is independent
      of whether the adaptation and test stimuli pose the same expressions. Like
      adults, children's representation of expression is identity-dependent (Vida &
      Mondloch, 2009). Here we investigated whether they have an expression-dependent
      representation of facial identity. Adults and 8-year-olds (n = 20 per group)
      categorized faces in an identity continuum (Sue/Jen) after viewing an adapting
      stimulus that displayed the same or a different emotional expression. Both groups
      showed identity aftereffects that were not influenced by facial expression. We
      conclude that, like adults, 8-year-old children's representation of identity is
      expression-independent.

PMID- 22847807
TI  - Masking and color inheritance along the apparent motion path.
AB  - Long-range  apparent motion is the illusory motion that can be perceived when two
      static and distant stimuli are presented in succession. Within some
      spatiotemporal range not only is motion sensed, but it appears as if one stimulus
      is displaced from one place to another (termed beta or optimal motion). Several
      groups have found that this illusory percept can interact with perception of a
      physically present stimulus, but some disagree on the origin of these
      interactions. We know little about how suppressive effects depend on feature
      similarity between a target and the stimuli in apparent motion (inducers)-which
      would indicate an early perceptual locus-or even about the minimal conditions
      under which to obtain this effect. Unlike early studies that used a two-stroke
      apparent motion paradigm, we were able to demonstrate that motion can mask
      stimuli presented at interpolated locations along the apparent motion path, as
      shown by the elevation of contrast thresholds compared to a control condition.
      Apparent motion masking depended on color similarity between target and inducers.
      Further, we found evidence that the color of inducers alters the apparent color
      of intervening gray probes, indicating some inheritance or chromatic averaging
      across distant locations, but no clear evidence of predictive updating. Finally,
      the analysis of the presentation times delivering maximal masking effects
      suggests a predictive interpolation process is responsible for interference by
      apparent motion filling-in. We discuss alternative mechanisms, in particular the
      possible role of apparent-motion-induced metacontrast masking in generating this
      pattern of results.

PMID- 22847808
TI  - Let-7 expression is a significant determinant of response to chemotherapy through
      the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma.
AB  - PURPOSE: Cisplatin-based chemotherapy is widely used for esophageal cancer,
      sometimes in combination with surgery/radiotherapy, but poor response to
      chemotherapy is not uncommon. The aim of this study was to examine whether miRNA
      expression is useful to predict the response to chemotherapy in patients with
      esophageal cancer. EXPERIMENTAL DESIGN: Using pretreatment biopsy samples from 98
      patients with esophageal cancer who received preoperative chemotherapy, we
      measured the expression level of several miRNAs whose expression was altered in
      cisplatin-resistant esophageal cancer cell lines compared with those parent cell
      lines and examined the relationship between the miRNA expression and response to
      chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA
      induced changes in chemosensitivity. RESULTS: The expression levels of 15 miRNAs
      were altered in cisplatin-resistant cells. Of these, low expression of let-7b and
      let-7c in before-treatment biopsies from 74 patients of the training set
      correlated significantly with poor response to chemotherapy, both clinically and
      histopathologically. Low expression of let-7c also correlated with poor prognosis
      (P = 0.032). The relationship between let-7b and let-7c expression and response
      to chemotherapy was confirmed in the other 24 patients of the validation set. In
      in vitro assay, transfection of let-7c restored sensitivity to cisplatin and
      increased rate of apoptosis after exposure to cisplatin. Let-7c directly
      repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway.
      CONCLUSIONS: Let-7 expression in esophageal cancer can be potentially used to
      predict the response to cisplatin-based chemotherapy. Let-7 modulates the
      chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in
      esophageal cancer.

PMID- 22847809
TI  - Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients
      with NY-ESO-1 expressing cancers: immunological effects and clinical activity.
AB  - PURPOSE: Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely
      defined preparation of heat-inactivated Streptococcus pyogenes and Serratia
      marcescens used as nonspecific immunotherapy in the treatment of cancer. The
      mechanism of action is suspected to have an immunologic basis, yet it is poorly
      defined up to now. We developed a new, biochemically well defined and current
      good manufacturing practice-compliant MBV preparation, which has been
      investigated in patients with NY-ESO-1 expressing cancers. EXPERIMENTAL DESIGN:
      Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin
      units) twice a week. The MBV dose was escalated in each patient until a body
      temperature of 38 degrees C to 39.5 degrees C was induced or up to the maximum
      dose of 547.000 EU. Changes in serum cytokine levels were determined and immune
      responses to NY-ESO-1 were evaluated. Tumor response was assessed according to
      RECIST. RESULTS: Twelve patients were enrolled and 11 of them developed fever
      after the administration of MBV. Ten of 12 patients showed a consistent increase
      in serum IL-6 levels with the highest levels coinciding with the highest body
      temperature. A subgroup of patients showed increasing levels of TNF-alpha, IFN
      gamma, and IL1-beta. A patient with metastatic bladder cancer showed a partial
      tumor response strongly correlated with MBV-induced fever and highly elevated
      levels of several cytokines. CONCLUSIONS: MBV at fever-inducing dose levels can
      lead to a massive induction of immunoregulatory cytokines that may be involved in
      inducing tumor regressions. We propose to further explore the role of MBV as a
      potent immune modulator at higher dose levels and in conjunction with antigen
      specific cancer vaccines.

PMID- 22847810
TI  - Different uses of plant semiochemicals in host location strategies of the two
      tachinid parasitoids.
AB  - Some members of the family Tachinidae (Insecta: Diptera) deposit numerous very
      small eggs, termed "microtype" eggs, on the food plants of their caterpillar
      hosts. Parasitization is successful only when the hosts ingest these eggs. To
      increase the chance of hosts encountering the eggs, microtype tachinid
      parasitoids have to choose a suitable plant that harbors hosts and lay their eggs
      near the hosts. In their host location process, semiochemicals emitted by host
      infested plants offer the tachinids a reliable cue. We investigated the
      behavioral responses of two microtype tachinid parasitoids, Pales pavida and
      Zenillia dolosa, to maize plants infested with their caterpillar host, Mythimna
      separata, in a wind tunnel. P. pavida females showed a significantly higher rate
      of landing on caterpillar-infested plants than on mechanically wounded or intact
      plants, whereas Z. dolosa landed on both the caterpillar-infested and
      mechanically wounded plants at significantly higher rates than on intact plants.
      We also examined which part of a caterpillar-infested maize leaf induces
      oviposition. P. pavida deposited eggs on the margin of the leaf, whereas Z.
      dolosa preferentially laid eggs around a caterpillar-infested area or a
      mechanically wounded spot. P. pavida eggs retained their parasitization ability
      for more than 15 days after they were deposited, whereas the eggs of Z. dolosa
      could not survive more than 5 days after oviposition. Our results suggest that
      each tachinid parasitoid employs a different host location strategy to exploit
      semiochemicals coming from plant-herbivore interaction as cues in order to
      increase their parasitization success.

PMID- 22847811
TI  - A critical review why assessment of steroid hormone receptors in breast cancer
      should be quantitative.
AB  - Steroid receptors have been around in the field of breast cancer for decades now.
      Still, controversy remains on how best to report steroid receptors. In this
      review, we will convince the reader why benefits outweigh pitfalls, when
      reporting steroid receptors in a quantitative rather than qualitative way.
      Summarizing decades of research in this field, we will explore the evidence why
      quantitative reporting is superior in all settings (neoadjuvant, adjuvant and
      metastatic settings). Furthermore, we will also summarize different staining
      methods, definitions and pitfalls that have shown to be important points of
      discussion in earlier debates. Although the molecular unraveling of breast cancer
      in the past decade has revolutionized the way we think about breast cancer, we
      should not easily abandon the classical pathological variables such as steroid
      receptors in favor of molecular tools.

PMID- 22847812
TI  - The incidence of esophageal adenocarcinoma continues to rise: analysis of period
      and birth cohort effects on recent trends.
AB  - BACKGROUND: During the past four decades, the incidence of esophageal
      adenocarcinoma (EAC) has increased markedly in Western populations. Recent
      reports have suggested that the rate of increase has slowed or plateaued.
      PATIENTS AND METHODS: Using data from cancer registries in Australia, the United
      States and Sweden, we examined incidence trends for esophageal and gastric cardia
      tumors between 1984 and 2008 using joinpoint analyses and age-period-cohort
      models. RESULTS: EAC incidence continues to undergo statistically significant
      annual increases in Australia and the United States, although the rate of
      increase has slowed. Among men, incidence increased annually by 2.2% [95%
      confidence interval (CI) 1.5% to 2.9%] between 1994 and 2008 in Australia and
      1.5% (95% CI 0.2% to 2.8%) between 1998 and 2008 in the United States. EAC
      incidence among men remained unchanged in Sweden between 2001 and 2008 (P =
      0.52). EAC incidence among women showed significant linear increases between 1984
      and 2008. Age-period-cohort models suggested strong effects for both period and
      birth cohort on EAC incidence in Australia and the United States, and a strong
      period effect for Sweden. CONCLUSIONS: EAC incidence continues to increase in
      Australia and the United States. The continued increases, even among more recent
      birth cohorts, suggest that EAC incidence will continue to rise during coming
      decades.

PMID- 22847813
TI  - Human placental transthyretin in fetal growth restriction in combination with
      preeclampsia and the HELLP syndrome.
AB  - Fetal growth restriction is a serious, still poorly understood pregnancy-related
      pathology often associated with preeclampsia. Recent studies speculate on the
      role of human transthyretin, a carrier protein for thyroxin and retinol binding
      protein, in the etiology of both pregnancy pathologies. Objective was to
      investigate the localization and abundance of transthyretin (TTR) in placentas of
      pregnancies suffering from fetal growth restriction with and without preeclampsia
      and HELLP. This was a retrospective case control study on human paraffin-embedded
      placentas from pregnancies with a gestational age at delivery between the 24th
      and 34th week of gestation. 16 placentas were included in this study, 11 cases
      and 5 from normotensive pregnancies as controls. Cases were divided into three
      groups: four from early onset idiopathic intrauterine growth restriction (IUGR),
      four from early-onset severe preeclampsia (PE), and three from early-onset IUGR
      with preeclampsia plus HELLP syndrome. Distribution and abundance of TTR were
      investigated by means of immunohistochemistry. Semi quantitative analysis of TTR
      staining of placental sections revealed that TTR was mostly expressed in the
      villous trophoblast covering placental villi. Only weak staining of TTR in
      villous stroma could be detected. The comparison of placentas revealed that in
      pure IUGR and severe PE there is a much stronger TTR reactivity compared to
      controls and cases with IUGR + PE + HELLP. Concluding, the study showed that TTR
      is dysregulated in cases of IUGR and severe early onset preeclampsia.
      Interestingly, TTR expression is not affected in cases with HELLP syndrome that
      reveal the same staining intensities as age-matched controls.

PMID- 22847814
TI  - [Decision of the Federal Joint Committee on screening for chorionicity - benefit
      assessment in the absence of screening studies].
AB  - The main decision-making body of the self-government system in Germany is the
      Federal Joint Committee (G-BA). In line with the principles of evidence-based
      medicine, randomised controlled trials with patient-relevant endpoints (in
      particular mortality, morbidity, quality of life) are preferred for the G-BA
      assessment of medical treatments and procedures. During this analysis of
      ultrasound screening for monochorionicity in multiple pregnancies, no studies
      were identified directly comparing a group with screening vs. a group without
      screening. Therefore, a 3-step process, which assesses the single components of
      screening (risk factors, relevant outcome for the patient, existence of a
      confirmed diagnosis, application of an effective therapy), was used. On the basis
      of these results the G-BA decided that the statutory health insurance should
      include the determination of chorionicity in their reimbursement catalogue.

PMID- 22847815
TI  - Box H/ACA snoRNAs are preferred substrates for the trimethylguanosine synthase in
      the divergent unicellular eukaryote Trichomonas vaginalis.
AB  - The 2,2,7-trimethylguanosine caps of eukaryal snRNAs and snoRNA are formed by the
      enzyme Tgs1, which catalyzes sequential guanine-N2 methylations of m(7)G caps.
      Atypically, in the divergent unicellular eukaryote Trichomonas vaginalis,
      spliceosomal snRNAs lack a guanosine cap and the recombinant T. vaginalis
      trimethylguanosine synthase (TvTgs) produces only m(2,7)G in vitro. Here, we show
      by direct metabolic labeling that endogenous T. vaginalis RNAs contain m(7)G,
      m(2,7)G, and m(2,2,7)G caps. Immunodepletion of TvTgs from cell extracts and
      TvTgs add-back experiments demonstrate that TvTgs produces m(2,7)G and m(2,2,7)G
      caps. Expression of TvTgs in yeast tgs1Delta cells leads to the formation of
      m(2,7)G and m(2,2,7)G caps and complementation of the lethality of a tgs1Delta
      mud2Delta strain. Whereas TvTgs is present in the nucleus and cytosol of T.
      vaginalis cells, TMG-containing RNAs are localized primarily in the nucleolus.
      Molecular cloning of anti-TMG affinity-purified T. vaginalis RNAs identified 16
      box H/ACA snoRNAs, which are implicated in guiding RNA pseudouridylation. The
      ensemble of new T. vaginalis H/ACA snoRNAs allowed us to predict and partially
      validate an extensive map of pseudouridines in T. vaginalis rRNA.

PMID- 22847816
TI  - The interaction between the yeast telomerase RNA and the Est1 protein requires
      three structural elements.
AB  - In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed
      of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and
      two regulatory proteins, Est1 and Est3. Previous work has identified a conserved
      5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1
      to TLC1. However, increased expression of Est1 can bypass the consequences of
      removal of this RNA bulge, indicating that there are additional binding site(s)
      for Est1 on TLC1. We report here that a conserved single-stranded internal loop
      immediately adjacent to the bulge is also required for the Est1-RNA interaction;
      furthermore, a TLC1 variant that lacks this internal loop but retains the bulge
      cannot be suppressed by Est1 overexpression, arguing that the internal loop may
      be a more critical element for Est1 binding. An additional structural feature
      consisting of a single-stranded region at the base of the helix containing the
      bulge and internal loop also contributes to recognition of TLC1 by Est1,
      potentially by providing flexibility to this helical arm. Association of Est1
      with each of these TLC1 motifs was assessed using a highly sensitive biochemical
      assay that simultaneously monitors the relative levels of the Est1 and Est2
      proteins in the telomerase complex. The identification of three elements of TLC1
      that are required for Est1 association provides a detailed view of this
      particular protein-RNA interaction.

PMID- 22847818
TI  - The last rRNA methyltransferase of E. coli revealed: the yhiR gene encodes
      adenine-N6 methyltransferase specific for modification of A2030 of 23S ribosomal
      RNA.
AB  - The ribosomal RNA (rRNA) of Escherichia coli contains 24 methylated residues. A
      set of 22 methyltransferases responsible for modification of 23 residues has been
      described previously. Herein we report the identification of the yhiR gene as
      encoding the enzyme that modifies the 23S rRNA nucleotide A2030, the last
      methylated rRNA nucleotide whose modification enzyme was not known. YhiR prefers
      protein-free 23S rRNA to ribonucleoprotein particles containing only part of the
      50S subunit proteins and does not methylate the assembled 50S subunit. We suggest
      renaming the yhiR gene to rlmJ according to the rRNA methyltransferase
      nomenclature. The phenotype of yhiR knockout gene is very mild under various
      growth conditions and at the stationary phase, except for a small growth
      advantage at anaerobic conditions. Only minor changes in the total E. coli
      proteome could be observed in a cell devoid of the 23S rRNA nucleotide A2030
      methylation.

PMID- 22847817
TI  - Recognition of guanosine by dissimilar tRNA methyltransferases.
AB  - Guanosines are important for biological activities through their specific
      functional groups that are recognized for RNA or protein interactions. One
      example is recognition of N(1) of G37 in tRNA by S-adenosyl-methionine (AdoMet)
      dependent tRNA methyltransferases to synthesize m(1)G37-tRNA, which is essential
      for translational fidelity in all biological domains. Synthesis of m(1)G37-tRNA
      is catalyzed by TrmD in bacteria and by Trm5 in eukarya and archaea, using
      unrelated and dissimilar structural folds. This raises the question of how
      dissimilar proteins recognize the same guanosine. Here we probe the mechanism of
      discrimination among functional groups of guanosine by TrmD and Trm5. Guanosine
      analogs were systematically introduced into tRNA through a combination of
      chemical and enzymatic synthesis. Single turnover kinetic assays and
      thermodynamic analysis of the effect of each analog on m(1)G37-tRNA synthesis
      reveal that TrmD and Trm5 discriminate functional groups differently. While both
      recognize N(1) and O(6) of G37, TrmD places a much stronger emphasis on these
      functional groups than Trm5. While the exocyclic 2-amino group of G37 is
      important for TrmD, it is dispensable for Trm5. In addition, while an adjacent
      G36 is obligatory for TrmD, it is nonessential for Trm5. These results depict a
      more rigid requirement of guanosine functional groups for TrmD than for Trm5.
      However, the sensitivity of both enzymes to analog substitutions, together with
      an experimental revelation of their low cellular concentrations relative to tRNA
      substrates, suggests a model in which these enzymes rapidly screen tRNA by direct
      recognition of G37 in order to monitor the global state of m(1)G37-tRNA.

PMID- 22847820
TI  - We are failing to identify disorders of fetal movement--why?

PMID- 22847819
TI  - Coat color determination by miR-137 mediated down-regulation of microphthalmia
      associated transcription factor in a mouse model.
AB  - Coat color is a key economic trait in wool-producing species. Color development
      and pigmentation are controlled by complex mechanisms in animals. Here, we report
      the first production of an altered coat color by overexpression of miR-137 in
      transgenic mice. Transgenic mice overexpressing miR-137 developed a range of coat
      color changes from dark black to light color. Molecular analyses of the
      transgenic mice showed decreased expression of the major target gene termed MITF
      and its downstream genes, including TYR, TYRP1, and TYRP2. We also showed that
      melanogenesis altered by miR-137 is distinct from that affected by UV radiation
      in transgenic mice. Our study provides the first mouse model for the study of
      coat color controlled by miRNAs in animals and may have important applications in
      wool production.

PMID- 22847821
TI  - A generalized relation for solid-state drug stability as a function of excipient
      dilution: temperature-independent behavior.
AB  - A proposed generalized relationship for the impact of excipients on the solid
      state chemical stability of drug products is presented and shown to be consistent
      across multiple degradation products with two example drugs. In this model, when
      the number of drug particles is comparable to the number of excipient particles,
      the impact of the excipient on the degradant formation rate is independent of
      drug concentration. In contrast, when the number of drug particles is in excess
      of the number of excipient particles, a power-law relation (linear correlation
      between the logarithm of the degradant formation rate and the logarithm of the
      reciprocal of the drug concentration) is proposed based on a "quasi-liquid" model
      where drug particles fill in interstices between excipients. As predicted by this
      model, the experimental power-law lines have slopes of about 2/3 independent of
      temperature (0.61 +/- 0.13 for n = 30 counting multiple degradation products and
      a range of temperatures and relative humidities for two drug products).

PMID- 22847822
TI  - A multidisciplinary approach and surgical tips in major amputations of diabetic
      patients.
AB  - We aim to describe the results obtained in major amputations (transtibial and
      transfemoral) of diabetic patients followed with a close combined approach
      (medical and surgical). We evaluated 37 cases with an average age of 73.55 years.
      All were admitted in our Diabetology Department where they were monitored and
      treated in order to reach a new balance concerning cardiac failure, anemia, and
      other pathologies. Then, the orthopedic surgeons operate choosing an adequate
      level for amputation and pointing about adequate stump covering, accurate vessel,
      perineural and periosteal hemostasis, and nerve thermoablation. Reading
      literature we discovered in our series an improvement concerning perioperative
      mortality, considering the high average age and the bad general conditions of our
      patients; at the same time, we obtained an improvement about neuromas and ghost
      limb syndrome versus literature. About walking capabilities we had similar
      results compared to previous papers, obtaining the worst results for thigh
      amputations.

PMID- 22847823
TI  - Gold-catalyzed one-step construction of 2,3-dihydro-1H-Pyrrolizines with an
      electron-withdrawing group in the 5-position: a formal synthesis of 7
      methoxymitosene.
AB  - What a ring formation! Bicyclic dihydropyrrolizines with an electron-withdrawing
      group (EWG) at the 5-position are formed in one step from linear azidoenynes
      under gold catalysis. This novel route involves the use of azide as a nitrene
      precursor, electronically-controlled regioselectivity, and the generation of
      destabilized 1-azapentadienium ions and their pericyclic reactions. This method
      was used for a formal synthesis of 7-methoxymitosene.

PMID- 22847824
TI  - Reconstruction of undersampled radial PatLoc imaging using total generalized
      variation.
AB  - In the case of radial imaging with nonlinear spatial encoding fields, a prominent
      star-shaped artifact has been observed if a spin distribution is encoded with an
      undersampled trajectory. This work presents a new iterative reconstruction method
      based on the total generalized variation, which reduces this artifact. For this
      approach, a sampling operator (as well as its adjoint) is needed that maps data
      from PatLoc k-space to the final image space. It is shown that this can be
      realized as a type-3 nonuniform fast Fourier transform, which is implemented by a
      combination of a type-1 and type-2 nonuniform fast Fourier transform. Using this
      operator, it is also possible to implement an iterative conjugate gradient SENSE
      based method for PatLoc reconstruction, which leads to a significant reduction of
      computation time in comparison to conventional PatLoc image reconstruction
      methods. Results from numerical simulations and in vivo PatLoc measurements with
      as few as 16 radial projections are presented, which demonstrate significant
      improvements in image quality with the total generalized variation-based
      approach.

PMID- 22847825
TI  - Novel biopolymer matrices for microencapsulation of phages: enhanced protection
      against acidity and protease activity.
AB  - Phage therapy by oral administration requires enhanced resistance of phages to
      the harsh gastric conditions. The aim of this work is the microencapsulation of
      phages in natural biopolymeric matrices as a protective barrier against the
      gastric environment. Alginate and pectin are used as base polymers. Further
      emulsification with oleic acid or coating with a different biopolymer is also
      studied. Emulsified pectin shows the maximum encapsulation efficiency and the
      highest protection against acidity, leaving more than 10(3) active phages after
      30 min exposure at pH = 1.6, and protects phage from pepsin activity (4.2 mg mL(
      1)). Non-encapsulated phages are fully inactivated at pH = 1.6 or with pepsin
      (0.5 mg mL(-1)) after 10 min.

PMID- 22847826
TI  - Immigrant status, antenatal depressive symptoms, and frequency and source of
      violence: what's the relationship?
AB  - This study describes the prevalence of violence during pregnancy and examines the
      association between the experience of violence since the beginning of pregnancy
      and the prevalence of antenatal depressive symptoms while taking into account
      immigrant status. Cross-sectional study including 5,162 pregnant women attending
      Montreal hospitals for antenatal care was conducted, with 1,400 being born
      outside of Canada. CES-D scale was used to evaluate depression at 24-26 weeks of
      pregnancy. The Abuse Assessment Screen scale was used to determine the frequency
      and severity of violence since the beginning of pregnancy. Relationship with
      abuser was also considered. All modeling was done using logistic regressions.
      Threats were the most frequent type of violence, with 63 % happening more than
      once. Long-term immigrant women reported the highest prevalence of all types of
      violence (7.7 %). Intimate partner violence (IPV) (15 %) was most frequently
      reported among the poorest pregnant women. Strong associations exist between more
      than one episode of abuse and depression (POR = 5.21 [3.73; 7.23], and IPV and
      depression [POR = 5.81 [4.19; 8.08]. Immigrant status did not change the
      associations between violence and depression. Violence against pregnant women is
      not rare in Canada, and it is associated with antenatal depressive symptoms.
      These findings support future development of perinatal screening for violence,
      follow-up, and a culturally sensitive referral system.

PMID- 22847828
TI  - Ocular anatomy and retinal photoreceptors in a skink, the sleepy lizard (Tiliqua
      rugosa).
AB  - The Australian sleepy lizard (Tiliqua rugosa) is a large day-active skink which
      occupies stable overlapping home ranges and maintains long-term monogamous
      relationships. Its behavioral ecology has been extensively studied, making the
      sleepy lizard an ideal model for investigation of the lizard visual system and
      its specializations, for which relatively little is known. We examine the
      morphology, density, and distribution of retinal photoreceptors and describe the
      anatomy of the sleepy lizard eye. The sleepy lizard retina is composed solely of
      photoreceptors containing oil droplets, a characteristic of cones. Two groups
      could be distinguished; single cones and double cones, consistent with
      morphological descriptions of photoreceptors in other diurnal lizards. Although
      all photoreceptors were cone-like in morphology, a subset of photoreceptors
      displayed immunoreactivity to rhodopsin-the visual pigment of rods. This finding
      suggests that while the morphological properties of rod photoreceptors have been
      lost, photopigment protein composition has been conserved during evolutionary
      history.

PMID- 22847827
TI  - The psychological profile and affective response of women diagnosed with
      unexplained infertility undergoing in vitro fertilization.
AB  - It has been hypothesized that unexplained infertility may be related to specific
      personality and coping styles. We studied two groups of women with explained
      infertility (EIF, n = 63) and unexplained infertility (UIF, n = 42) undergoing an
      in vitro fertilization (IVF) cycle. Women completed personality and coping style
      questionnaires prior to the onset of the cycle, and state depression and anxiety
      scales before and at two additional time points during the cycle. Almost no in
      between group differences were found at any of the measured time points in
      regards to the Minnesota Multiphasic Personality Inventory-2 validity and
      clinical scales, Illness Cognitions and Life Orientation Test, or for the
      situational measures. The few differences found suggest a more adaptive, better
      coping, and functioning defensive system in women with EIF. In conclusion, we did
      not find any clinically significant personality differences or differences in
      depression or anxiety levels between women with EIF and UIF during an IVF cycle.
      Minor differences found are probably a reaction to the ambiguous medical
      situation with its uncertain prognosis, amplifying certain traits which are not
      specific to one psychological structure but rather to the common experience
      shared by the group. The results of this study do not support the possibility
      that personality traits are involved in the pathophysiology of unexplained
      infertility.

PMID- 22847829
TI  - Bisphenol-A affects the developmental progression and expression of heat-shock
      protein genes in the moth Sesamia nonagrioides.
AB  - The effects of bisphenol A (BPA) on the endocrine system of vertebrates have been
      demonstrated in several studies. Here, we report the impact of BPA on the
      developmental progression and expression of heat shock protein genes on the
      terrestrial insect Sesamia nonagrioides (Lepidoptera: Noctuidae). S. nonagrioides
      1st instar larvae were exposed until the end of 6th (last) instar to selected
      concentrations of BPA (1 MUg/L, 10 MUg/L, 100 MUg/L, 1 mg/L and 10 mg/L) applied
      in their artificial diets. The lower doses of BPA (1-10 MUg/L) were found to
      decrease larvae's weight while the 100 MUg/L dose increased it. The higher doses
      of BPA were found to induce various abnormal phenotypes during 5th instar larval
      molting, larval-pupal transformation and metamorphosis. The developmental and
      metamorphosis endpoints presented here may indicate the possible impact of BPA on
      terrestrial insects. Additionally, 6th instar larvae were injected with several
      concentrations of BPA. Semi-quantitative and Real-Time PCR assays were used to
      identify the effects of BPA in the transcriptional regulation of five heat shock
      protein genes (SnoHsp19.5, SnoHsp20.8, SnoHsp70, SnoHsc70 and SnoHsp83).
      Application of BPA by feeding or by injection induced the synthesis of the
      SnoHsp19.5 and SnoHsp20.8 mRNAs. The expression levels of SnoHsp70 were not
      affected. In contrast, SnoHsc70 and SnoHsp83, which play a pivotal role in
      vertebrate sex steroid signal transduction, were elevated by BPA. Our results
      suggest that SnoHsp19.5, SnoHsp20.8, SnoHsp83 and SnoHsc70 genes can be modulated
      by BPA.

PMID- 22847830
TI  - Dietary (periphyton) and aqueous Zn bioaccumulation dynamics in the mayfly
      Centroptilum triangulifer.
AB  - Diet is often the predominant route of trace metal exposure in aquatic insects.
      In freshwater ecosystems, periphyton serves as a primary source of food to many
      aquatic insects and is a major sink for trace metals. We investigated the
      bioconcentration of the essential metal Zn by periphyton using (65)Zn as a
      radiotracer. At relatively low dissolved concentrations (2-20 MUg L(-1)), non
      steady state Zn bioconcentration by periphyton averaged 6,099 +/- 2,430-fold,
      with much of the variability determined by loading regime (number of renewals and
      duration of exposures). Labeled periphyton was used as a food source for dietary
      accumulation studies with the mayfly Centroptilum triangulifer. After 29 days,
      larvae concentrated Zn 19-, 16- and 17-fold relative to dietary Zn concentrations
      of 8.1, 43.2 and 82.3 MUg g(-1) (dry weight), respectively. Adults from that same
      cohort only concentrated Zn 8-, 3- and 3- fold relative to those same dietary
      concentrations, revealing that mayflies lose significant Zn prior to reaching
      adulthood. Anecdotal evidence suggests that this loss occurs prior to emergence
      to the subimago, as negligible Zn was found in the subimago to imago exuvium.
      Across a range of adult tissue concentrations, maternal transfer consistently
      averaged 26.7 %. Uptake (k(u), 0.26 L g(-1 )d(-1)) and efflux rate constants
      (k(e), 0.001-0.007 d(-1)) were measured and assimilation efficiencies from
      dietary Zn concentrations of 4.9 and 59.7 MUg Zn g(-1) were estimated to be 88 +/
      4 % and 64 +/- 15 %, respectively. Both life cycle and biodynamic modeling
      approaches point towards diet being the primary route of Zn bioaccumulation in
      this mayfly.

PMID- 22847831
TI  - Trenbolone causes mortality and altered sexual differentiation in Xenopus
      tropicalis during larval development.
AB  - Trenbolone is an androgen agonist used in cattle production and has been measured
      in aquatic systems associated with concentrated animal-feeding operations. In
      this study, the authors characterized the effects of aqueous exposure to 17beta
      trenbolone during larval Xenopus tropicalis development. Trenbolone exposure
      resulted in increased mortality of post-Nieuwkoop-Faber stage 58 tadpoles at
      concentrations >=100 ng/L. Morphological observations and the timing of this
      mortality are consistent with hypertrophy of the larynx. Development of nuptial
      pads, a male secondary sex characteristic, was induced in tadpoles of both sexes
      at 100 ng/L. Effects on time to complete metamorphosis or body sizes were not
      observed; however, grow-outs placed in clean media for six weeks were
      significantly smaller in body size at 78 ng/L. Effects on sex ratios were
      equivocal, with the first experiment showing a significant shift in sex ratio
      toward males at 78 ng/L. In the second experiment, no significant effects were
      observed up to 100 ng/L, although overall sex ratios were similar. Histological
      assessment of gonads at metamorphosis showed half with normal male phenotypes and
      half that possessed a mixed-sex phenotype at 100 ng/L. Hypertrophy of the
      Wolffian ducts was also observed at this concentration. These results indicate
      that larval 17beta-trenbolone exposure results in effects down to 78 ng/L,
      illustrating potential effects from exposure to androgenic compounds in anurans.

PMID- 22847833
TI  - Highly stereoselective synthesis of tertiary propargylic centers and their
      isomerization to enantiomerically enriched allenes.

PMID- 22847835
TI  - Evidence of an oxidative-addition-promoted Pd-leaching mechanism in the Suzuki
      reaction by using a Pd-nanostructure design.

PMID- 22847834
TI  - Pd-catalyzed modifiable silanol-directed aromatic C-H oxygenation.

PMID- 22847837
TI  - Auditory characteristics and therapeutic effects of enzyme replacement in mouse
      model of the mucopolysaccharidosis (MPS) II.
AB  - Mucopolysaccharidosis (MPS) II is an X-linked metabolic disorder caused by
      dysfunction of iduronate-2-sulfatase (I2S). This abnormality causes the
      progressive accumulation of incompletely degraded glycosaminoglycans (GAGs) in
      the lysosomes. The auditory characteristics of MPS II in mouse models have not
      been reported. In this study, we evaluated the auditory characteristics of the
      MPS II in IDS knock-out (IDS-KO) mice. In addition, the effect of enzyme
      replacement therapy (ERT) on hearing was studied. The IDS-KO mice had normal
      histology of the cochlea and retained good hearing at 7 weeks of age. However, at
      17 weeks of age, the hearing thresholds of the IDS-KO mice were elevated and
      exudates were found in the middle ear. The hearing thresholds of the enzyme
      treated IDS-KO (IDS-ERT) mice were similar to the wild-type (WT) mice at 17
      weeks. Moreover, the microstructure of the inner ear was similar to the IDS-KO by
      transmission electron microscopy. The histology findings indicated that the
      microstructure of the inner ear was similar in comparisons between IDS-KO and IDS
      ERT mice, even after 10 weeks of treatment. However, the hearing deficits in the
      MPS II mouse model can be prevented if ERT is started before the onset of hearing
      impairment.

PMID- 22847838
TI  - Interplay between protein-modified surface and functional response of
      osteoblasts.
AB  - The objective of the study is to elucidate the interplay between fibronectin
      metal hybrid surfaces and osteoblast function. The practical relevance is that a
      significant initial step in the process of prosthetic integration within a
      physiological system is the rapid adsorption of proteins, including fibronectin,
      on the surface of biomedical device. Here, we compare and contrast the cell
      substrate interactions on bare and protein-modified surfaces. The protein
      adsorption on the surface was beneficial in favorably modulating biological
      functions including cell attachment, proliferation, and viability. Additionally,
      immunofluorescence studies demonstrated stronger vinculin signals associated with
      actin stress fibers in the outer regions of the cells and cellular extensions on
      protein-adsorbed surfaces. These results support the hypothesis that protein
      adsorption on artificial biomedical devices can promote bioactivity and regulate
      biological functions.

PMID- 22847839
TI  - Successful treatment for Cronkhite-Canada syndrome with endoscopic mucosal
      resection and salazosulfapyridine.
AB  - A 79-year-old woman was referred to our hospital because numerous polyps were
      found in her stomach and large intestine at an ambulatory clinic. Although there
      were no characteristic symptoms or signs of Cronkhite-Canada syndrome (CCS),
      endoscopic and pathological findings indicated CCS. Moreover, colonoscopy showed
      two polypoid lesions (Is type), which appeared neoplastic by magnifying
      observation with image-enhanced endoscopy (IEE), in the ascending colon.
      Histologically, the resected specimens revealed tubular adenomas arising in the
      CCS inflammatory polyps. Remarkable remission of the polyps and edematous mucosa
      in the stomach and colon was seen after 8 months of administration of
      salazosulfapyridine (SASP) (3 g/day). Another adenoma was detected and removed
      endoscopically in the sigmoid colon. This is the first report to describe an
      asymptomatic case of CCS probably detected in the early phase of the disease, by
      magnifying IEE which enabled detection and treatment for associated colonic
      adenomas. SASP was effective in eradication of the inflammatory polyposis, and an
      additional adenoma was successfully found and removed by surveillance colonoscopy
      thereafter.

PMID- 22847840
TI  - Intercurrent infection predicts mortality in patients with late hepatic artery
      thrombosis listed for liver retransplantation.
AB  - Liver retransplantation for late hepatic artery thrombosis (HAT) is considered
      the treatment of choice for select patients. Nevertheless, there is a paucity of
      data to aid decision making in this setting. The aims of this single-center study
      of patients listed for late HAT were (1) to determine variables associated with
      wait-list mortality, (2) to describe survival after retransplantation, and (3) to
      determine variables associated with mortality after retransplantation. Seventy
      eight patients were diagnosed with late HAT (incidence = 3.9%). Of the 49
      patients listed for retransplantation, 9 died on the waiting list and 36 were
      retransplanted. The estimated 1-year survival after listing for retransplantation
      was 53.7%. Only multidrug-resistant (MDR) bacteria-positive cultures were
      predictive of wait-list mortality (P = 0.01). After retransplantation, the
      estimated 1- and 5-year patient survival was 71.9% and 62.5%, respectively.
      Increasing Model for End-Stage Liver Disease score (overall P = 0.007), MDR
      bacteria-positive cultures (P = 0.047), and continued antibiotic therapy (P =
      0.001) at the time of retransplantation were risk factors for post retransplant
      death. In conclusion, patients who undergo liver retransplantation for late HAT
      have satisfactory outcomes. However, the presence of active infection and MDR
      bacteria-positive cultures should be taken into account when risk stratifying
      such patients.

PMID- 22847841
TI  - The application of quantification techniques in proteomics for biomedical
      research.
AB  - The systematic analysis of biological processes requires an understanding of the
      quantitative expression patterns of proteins, their interacting partners and
      their subcellular localization. This information was formerly difficult to accrue
      as the relative quantification of proteins relied on antibody-based methods and
      other approaches with low throughput. The advent of soft ionization techniques in
      mass spectrometry plus advances in separation technologies has aligned protein
      systems biology with messenger RNA, DNA, and microarray technologies to provide
      data on systems as opposed to singular protein entities. Another aspect of
      quantitative proteomics that increases its importance for the coming few years is
      the significant technical developments underway both for high pressure liquid
      chromatography and mass spectrum devices. Hence, robustness, reproducibility and
      mass accuracy are still improving with every new generation of instruments.
      Nonetheless, the methods employed require validation and comparison to design fit
      for purpose experiments in advanced protein analyses. This review considers the
      newly developed systematic protein investigation methods and their value from the
      standpoint that relative or absolute protein quantification is required de
      rigueur in biomedical research.

PMID- 22847842
TI  - Unique interaction between directly linked laminated pi planes in the
      benzonorrole dimer.

PMID- 22847843
TI  - Nonlinear optical imaging for sensitive detection of crystals in bulk amorphous
      powders.
AB  - The primary aim of this study was to evaluate the utility of second-order
      nonlinear imaging of chiral crystals (SONICC) to quantify crystallinity in drug
      polymer blends, including solid dispersions. Second harmonic generation (SHG) can
      potentially exhibit scaling with crystallinity between linear and quadratic
      depending on the nature of the source, and thus, it is important to determine the
      response of pharmaceutical powders. Physical mixtures containing different
      proportions of crystalline naproxen and hydroxyl propyl methyl cellulose acetate
      succinate (HPMCAS) were prepared by blending and a dispersion was produced by
      solvent evaporation. A custom-built SONICC instrument was used to characterize
      the SHG intensity as a function of the crystalline drug fraction in the various
      samples. Powder X-ray diffraction (PXRD) and Raman spectroscopy were used as
      complementary methods known to exhibit linear scaling. SONICC was able to detect
      crystalline drug even in the presence of 99.9 wt % HPMCAS in the binary mixtures.
      The calibration curve revealed a linear dynamic range with a R(2) value of 0.99
      spanning the range from 0.1 to 100 wt % naproxen with a root mean square error of
      prediction of 2.7%. Using the calibration curve, the errors in the validation
      samples were in the range of 5%-10%. Analysis of a 75 wt % HPMCAS-naproxen solid
      dispersion with SONICC revealed the presence of crystallites at an earlier time
      point than could be detected with PXRD and Raman spectroscopy. In addition,
      results from the crystallization kinetics experiment using SONICC were in good
      agreement with Raman spectroscopy and PXRD. In conclusion, SONICC has been found
      to be a sensitive technique for detecting low levels (0.1% or lower) of
      crystallinity, even in the presence of large quantities of a polymer.

PMID- 22847848
TI  - Center-out echo-planar spectroscopic imaging with correction of gradient-echo
      phase and time shifts.
AB  - A procedure to prevent the formation of image and spectral Nyquist ghosts in echo
      planar spectroscopic imaging is introduced. It is based on a novel Cartesian
      center-out echo-planar spectroscopic imaging trajectory, referred to as EPSICO,
      and combined with a correction of the gradient-echo phase and time shifts.
      Processing of homogenous sets of forward and reflected echoes is no longer
      necessary, resulting in an optimized spectral width. The proposed center-out
      trajectory passively prevents the formation of Nyquist ghosts by privileging the
      acquisition of the center k-space line with forward echoes at the beginning of an
      echo-planar spectroscopic imaging dwell time and by ensuring that all k-space
      lines and their respective complex conjugates are acquired at equal time
      intervals. With the proposed procedure, concentrations of N-acetyl aspartate,
      creatine, choline, glutamate, and myo-inositol were reliably determined in human
      white matter at 3 T.

PMID- 22847849
TI  - First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery
      Doppler, and maternal characteristics.
AB  - OBJECTIVE: The objective of this study was to estimate the efficiency of first
      trimester a disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated
      plasma protein A (PAPP-A), uterine artery Doppler, and maternal characteristics
      in the prediction of preterm birth (PTB). METHODS: This was a prospective cohort
      study of patients presenting for first-trimester aneuploidy screening. Maternal
      serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine
      artery Doppler pulsatility indices were calculated. The primary outcome was PTB
      <34 weeks' gestation, and the secondary outcome was PTB <37 weeks' gestation.
      Logistic regression was used to model the prediction of PTB using ADAM12, PAPP-A,
      uterine artery Doppler, and maternal characteristics, individually and in
      combination. Sensitivity, specificity, and area under the receiver-operating
      characteristic curves were compared between models. RESULTS: Of 578 patients, 36
      (6.2%) delivered <34 weeks, and 78 (13.5%) delivered <37 weeks. For a 20% fixed
      false positive rate, ADAM12, PAPP-A, and uterine artery Doppler identified 58%,
      52%, and 62% of patients with PTB <34 weeks and 42%, 48%, and 50% of patients
      with PTB <37 weeks, respectively. Combining these first-trimester parameters did
      not improve the predictive efficiency of the models. CONCLUSION: First-trimester
      ADAM12, PAPP-A, and uterine artery Doppler are each modestly predictive of PTB;
      however, combinations of these parameters do not further improve their screening
      efficiency.

PMID- 22847850
TI  - Prolactinoma: a condition associated with hypoadiponectinemia.
AB  - Prolactinomas are prolactin-secreting neoplasias accounting for 40% of the
      pituitary adenomas. Much is known about the effects of prolactinomas on the
      reproductive system, but few data are yet available regarding their induced
      changes on metabolism. This study was aimed at evaluating patients with
      prolactinomas for insulin resistance and adiponectinemia. Forty patients with
      prolactinoma were allocated to 2 different groups according to disease control:
      20 with uncontrolled disease (UPRL) and 20 with controlled disease in the last 6
      months (CPRL). Forty healthy individuals (CG) matched for age, sex, and body mass
      index were taken as controls. Patients with prolactinoma were compared both as a
      one group and according to disease control with CG. All subjects were evaluated
      for waist/hip ratio (WHR), blood pressure, lipid profile, fasting glucose,
      homeostasis assessment model of insulin resistance (HOMAIR), and adiponectin.
      Patients with prolactinomas (UPRL+CPRL) showed higher insulin (p<0.05) and HOMAIR
      (p<0.05), alongside with lower adiponectin levels (p<0.01) than matched controls.
      When UPRL was compared to CPRL and CG, UPRL was disclosed as a subgroup of
      significant altered metabolic profile as related to WHR (p<0.01 for comparisons),
      high-density lipoprotein cholesterol (p<0.05 for comparisons), triglycerides
      (p<0.05 for comparisons), HOMAIR (p<0.05 and p<0.01, respectively), and
      adiponectin (p<0.01 for comparisons). All these metabolic abnormalities, except
      hypoadiponectinemia (p<0.01), were not observed in CPRL. These data suggest that
      prolactinomas are associated with hypoadiponectinemia, which is further
      exacerbated in uncontrolled patients when insulin resistance is also prominent.

PMID- 22847851
TI  - Insulin resistant phenotype of polycystic ovary syndrome does not seem to be
      caused by variation in FTO.
AB  - Genetic variation in the FTO gene is associated with increased body weight and
      reduced insulin sensitivity. We investigated whether genetic variation in FTO is
      associated with polycystic ovary syndrome (PCOS), a condition also characterized
      by insulin resistance. Furthermore, we tested whether insulin resistance is
      specifically associated with genetic variation in FTO in women with PCOS. Sixty
      two nondiabetic patients with PCOS defined by the Rotterdam criteria were
      compared to BMI and age-matched women. Each PCOS case was matched to 2 controls.
      All participants underwent an oral glucose tolerance test and were genotyped for
      the single nucleotide polymorphism rs8050136 in the FTO gene. There was no
      difference in the frequency of FTO genotypes between the PCOS and the non-PCOS
      groups. In non-PCOS participants, genetic variation in FTO is associated with
      insulin sensitivity (p=0.03). This association remained significant after
      adjustment for age and/or BMI (p<= 0.03). In subjects with PCOS, however, FTO did
      not associate with insulin sensitivity (p=0.67). Genetic variation in FTO does
      not have an impact on insulin sensitivity in women with PCOS and is therefore not
      involved in the pathogenesis of the insulin resistant phenotype seen in patients
      with PCOS.

PMID- 22847852
TI  - Fabrication of nanofiber scaffolds with gradations in fiber organization and
      their potential applications.
AB  - A new and simple method for fabrication of nanofiber scaffolds with gradations in
      fiber organization is reported. The nanofiber organization, achieved by
      deposition of random fibers on the uniaxially aligned nanofiber mat in a gradient
      manner, directed morphological changes of applied adipose-derived stem cells.
      These morphological changes and resultant biochemical changes can help mimic the
      structural orientation of complex biomechanical structures like the collagen
      fiber structure at the tendon-to-bone insertion site. In addition, chemical
      gradients can be established through nanoencapsulation in this novel scaffold
      allowing for enhanced biomedical applications.

PMID- 22847854
TI  - Accuracy of digital models obtained by direct and indirect data capturing.
AB  - OBJECTIVES: With direct and indirect digitalisation, two access points to CAD/CAM
      generated restorations are available. The aim of this study was to compare the
      accuracy of the single steps of both approaches by comparing construction
      datasets using a new methodology. MATERIAL AND METHOD: Twelve test datasets were
      generated in vitro (1) with the Lava Chairside Oral Scanner (COS) (2) by
      digitizing polyether impressions (IMP) and (3) by scanning the referring gypsum
      cast by the Lava Scan ST laboratory scanner (ST) at a time. Using an inspection
      software, these datasets were superimposed by a best fit algorithm with the
      reference dataset (REF), gained from industrial computed tomography, and
      divergences were analysed. RESULTS: On the basis of average positive and negative
      deviations between test- and REF datasets, it could be shown that direct
      digitalisation accomplished the most accurate results (COS, 17 MUm/-13 MUm; SD +/
      19 MUm), followed by digitized polyether impression (IMP, 23 MUm/-22 MUm; SD +/-
      31 MUm) and indirect digitalisation (ST, 36 MUm/-35 MUm; SD +/- 52 MUm). The mean
      absolute values of Euclidean distances showed the least values for COS (15 MUm;
      SD +/- 6 MUm), followed by IMP (23 MUm; SD +/- 9 MUm) and ST (36 MUm; SD +/- 7
      MUm). The mean negative and mean absolute values of all groups were significantly
      different. Comparing the mean positive values of the groups, IMP and COS (p =
      0.082) showed no significant difference, whereas ST and COS, and ST and IMP
      exhibited statistically significant differences. CONCLUSIONS: Within the
      limitations of this in vitro study, the direct digitalisation with Lava C.O.S.
      showed statistically significantly higher accuracy compared to the conventional
      procedure of impression taking and indirect digitalisation. CLINICAL RELEVANCE:
      Within the limitations of this study, the method of direct digitalisation seems
      to have the potential to improve the accuracy of impressions for four-unit FDPs.

PMID- 22847855
TI  - Factors determining the retentiveness of luting agents used with metal- and
      ceramic-based implant components.
AB  - OBJECTIVES: To investigate the factors that determine the retentiveness of
      copings made of cobalt-chromium (CoCr)-alloy or zirconia luted with permanent
      (solid-body like) and provisional (viscous, elastic-body-like) luting agents.
      MATERIALS AND METHODS: We manufactured titanium implant analogs with four-, six-,
      and eight-taper degrees and copings of CoCr-alloy and zirconia and luted the
      copings according to a standardized protocol. Samples were thermally cycled, and
      we investigated the various degrees of roughness of the copings' inner surfaces
      as well as the various cement mixing ratios on the retentiveness. Copings were
      either pulled out slowly (by means of a universal testing machine) or knocked out
      quickly (using a CORONAflex crown replacement device). RESULTS: The highest level
      of retentiveness was achieved with a four-taper degree for polycarboxylates
      followed by zinc-oxide-phosphates and glass ionomers or composite cements.
      Provisional cements and composite cements containing a plastifier showed
      significantly lower retentiveness levels. The pull-out and knock-out tests showed
      a relationship between retentiveness level and taper degree. However, the
      influence of taper degree was reduced with higher taper degrees as well as with
      cements that do not set as a solid body due to ingredients such as oily liquids
      or plastifiers. Thermal cycling further reduced the retentiveness level of these
      cements. Higher degrees of roughness only improved the retention force of cements
      setting as a solid body. Mixing errors may alter retentiveness levels in an
      unpredictable manner. When used within the same group of cements, metal-alloy,
      and zirconia copings did not differ with regard to their level of retentiveness.
      CONCLUSION: Copings made of metal-alloy and zirconia showed no different level of
      retentiveness when set onto titanium abutments fixed with permanent or
      provisional cements. CLINICAL RELEVANCE: Only cements setting as a solid body
      showed a clear relationship between retentiveness level and taper degree. In
      contrast, the retentiveness of provisional (viscous, elastic-body-like) luting
      agents was less predictable.

PMID- 22847856
TI  - Non-surgical periodontal therapy influences salivary melatonin levels.
AB  - OBJECTIVES: Melatonin is a hormone, which is involved in the control of the
      circadian rhythm, but also acts as an antioxidant and immune modulator. Previous
      studies reported decreased salivary and serum melatonin levels in periodontitis.
      This prospective cohort trial assessed the effect of non-surgical periodontal
      therapy on melatonin levels. METHODS: Salivary and serum samples of 60
      participants (30 patients suffering from a severe generalized form of
      periodontitis, 30 healthy controls) were collected at baseline and 19 samples of
      periodontitis patients after treatment. Salivary and serum melatonin levels were
      determined by a commercially available ELISA kit and serum C-reactive protein
      (CRP) by a routine laboratory test. RESULTS: At baseline, periodontitis patients
      showed significantly increased serum CRP values and significantly decreased
      salivary melatonin levels compared to the control group. Clinical periodontal
      parameters significantly correlated with salivary melatonin levels and serum CRP.
      Periodontal therapy resulted in a recovery of the decreased salivary melatonin
      levels and a negative correlation was detected for the changes of salivary
      melatonin and the inflammatory parameter bleeding on probing. Serum melatonin
      levels showed no significant differences. CONCLUSIONS: Salivary melatonin levels
      recovered after periodontal therapy and correlated with a decrease of local
      periodontal inflammation. This may imply the local involvement of melatonin in
      the pathogenesis of periodontitis due to its antioxidant abilities. However, the
      exact role of melatonin in periodontal disease remains to be investigated in
      future trials. CLINICAL RELEVANCE: The present results suggest salivary melatonin
      as a risk indicator for the severity of periodontal disease.

PMID- 22847858
TI  - Nonlinear absorbing platinum(II) diimine complexes: synthesis, photophysics, and
      reverse saturable absorption.
AB  - A series of platinum(II) diimine complexes with different substituents on
      fluorenyl acetylide ligands (1a-1e) were synthesized and characterized. The
      influence of the auxiliary substituent on the photophysics of these complexes has
      been systematically investigated spectroscopically and theoretically (using
      density functional theory (DFT) methods). All complexes exhibit ligand-centered
      (1)pi,pi* transitions in the UV and blue spectral region, and broad,
      structureless (1)MLCT/(1)LLCT (1a, 1b, 1d and 1e) or (1)MLCT/(1)LLCT/(1)pi,pi*
      (1c) absorption bands in the visible region. All complexes are emissive in
      solution at room temperature, with the emitting state is tentatively assigned to
      mixed (3)MLCT/(3)pi,pi* states. The degree of (3)pi,pi* and (3)MLCT mixing varies
      with different substituents and solvent polarities. Complexes 1a-1e exhibit
      relatively strong singlet and triplet transient absorption from 450 to 800 nm, at
      which point reverse saturable absorption (RSA) could occur. Nonlinear
      transmission experiments at 532 nm by using nanosecond laser pulses demonstrate
      that 1a-1e are strong reverse saturable absorbers and could potentially be used
      as broadband nonlinear absorbing materials.

PMID- 22847857
TI  - Proliferation and osteogenic differentiation of osteoblast-like cells obtained
      from two techniques for harvesting intraoral bone grafts.
AB  - OBJECTIVES: The aims of our study were to verify the presence of viable
      osteoblasts in samples of bone tissue obtained by drilling or from cortico
      cancellous bone blocks and to assess their growth and differentiation capacities.
      MATERIALS AND METHODS: Bone tissue samples were processed independently and
      cultured in Dulbecco's modified Eagle medium, in a CO2 incubator at 37  degrees
      C. The proliferative capacity of osteoblasts was determined by spectrophotometry
      (MTT) at 24 and 48 h of culture. Cell cycle was analysed by flow cytometry. Cell
      differentiation was studied by red alizarin staining of nodules formed in
      mineralisation medium and by analysis of alkaline phosphatase activity. RESULTS:
      In comparison to bone block-derived osteoblasts, the proliferative capacity was
      greater at 24 and 48 h of culture (P < 0.001) in the drilling-derived
      osteoblasts, which showed significantly increased G2/M (P = 0.014) and S (P <
      0.001) phases in the cell cycle study. The number of mineralised nodules was
      proportional to the incubation time, with no differences between the two types of
      sample, which also did not significantly differ in alkaline phosphatase activity.
      CONCLUSION: Superior autograft material is obtained by harvesting particulate
      bone from low-speed drilling fragments than from a cortico-cancellous bone block.
      CLINICAL RELEVANCE: These results suggest that bone obtained from low-speed
      drilling is a simple and effective alternative to the classic procedure for
      obtaining bone tissue.

PMID- 22847859
TI  - Efficacy of platelet-rich plasma gel and hyaluronan hydrogel as carriers of
      electrically polarized hydroxyapatite microgranules for accelerating bone
      formation.
AB  - The technology for electrical polarization and characterization of hydroxyapatite
      (HA) microgranules has been developed. This study aimed to examine and compare
      the efficacy of composites comprising electrically polarized HA (pHA)
      microgranules and platelet-rich plasma (PRP) or hyaluronan (HAN) in
      osteoconductivity. Composites of HA microgranules with or without electrical
      polarization and either PRP or HAN (PRP+pHA, PRP+HA, HAN+pHA, and HAN+HA,
      respectively), as well as pHA and HA microgranules were implanted randomly into
      holes created in the medial femoral condyle or tibial tuberosity of rabbits. As a
      control, PRP or HAN gel alone was implanted, or the bone holes were left empty.
      Each group included six animals. After 6 weeks, histological examination was
      performed, and osteoclastic and osteoblastic cell activities were assessed by
      cell counting. Although PRP alone could not induce bone formation, PRP+pHA and
      PRP+HA composites, especially the former, activated osteogenic cells and enhanced
      bone formation. This effect was not prominent in the HAN+pHA and HAN+HA
      composites. PRP+HA composites formed a gel in which the ceramic particles were
      dispersed and entrapped in the fibrin network of PRP. It is assumed that these
      particles provide scaffolds for osteogenic cells, and when electrically
      polarized, can activate the cells in co-operation with the positive effects of
      the PRP, resulting in enhanced bone formation. Conversely, it is conceivable that
      this composite gel cannot act as an accelerator for woven bone formation, because
      HAN with low viscoelasticity is absorbed rapidly after implantation, the hydrated
      network containing HA microgranules is destroyed, and the HA microgranules effuse
      with HAN from the bone hole.

PMID- 22847860
TI  - Pathogenic infection confounds induction of the estrogenic biomarker vitellogenin
      in rainbow trout.
AB  - To examine the behavior of the estrogenic biomarker vitellogenin (VTG) under the
      combined impact of estrogens and pathogens, parasite-infected or noninfected
      rainbow trout were exposed to two doses of 17beta-estradiol (E2). Infected and E2
      exposed fish showed significantly lower hepatic VTG mRNA levels than healthy
      fish. Transcriptome data suggest that this was due to energetic constraints.
      Reduced responsiveness of the VTG biomarker in parasitized fish might obscure
      detection of low-level field exposure.

PMID- 22847861
TI  - Dual cytoprotective effects of splenectomy for small-for-size liver
      transplantation in rats.
AB  - The problems associated with small-for-size liver grafts (ie, high mortality
      rates, postoperative complications, and acute rejection) remain critical issues
      in partial orthotopic liver transplantation (OLT). In association with partial
      OLT, splenectomy (SP) is a procedure used to reduce the portal pressure. However,
      the precise effects of SP on partial OLT have been unclear. In this study, using
      small-for-size liver grafts in rats, we examined the cytoprotective effects of SP
      on OLT. Liver grafts were assigned to 2 groups: a control group (OLT alone) and
      an SP group (OLT after SP). SP significantly increased animal survival and
      decreased liver damage. SP exerted the following cytoprotective effects: (1) it
      improved hepatic microcirculation and prevented increases in the portal pressure
      after OLT, (2) it suppressed the hepatic infiltration of neutrophils and
      macrophages through the direct elimination of splenic inflammatory cells before
      OLT, (3) it decreased the hepatic expression of tumor necrosis factor alpha and
      interleukin-6, (4) it attenuated sinusoidal endothelial injury, (5) it decreased
      plasma endothelin 1 levels and increased hepatic heme oxygenase 1 expression, (6)
      it suppressed hepatocellular apoptosis through the down-regulation of hepatic
      caspase-3 and caspase-8 activity, and (7) it increased hepatic regeneration. In
      conclusion, SP for small-for-size grafts exerts dual cytoprotective effects by
      preventing excessive portal vein hepatic inflow and eliminating splenic
      inflammatory cell recruitment into the liver; this in turn inhibits
      hepatocellular apoptosis and improves liver regeneration.

PMID- 22847862
TI  - Attributable risk estimation for adjusted disability multistate models:
      application to nosocomial infections.
AB  - Attributable risk has become an important concept in clinical epidemiology. In
      this paper, we suggest to estimate the attributable risk of nosocomial infections
      using a multistate approach. Recently, a multistate model (called progressive
      disability model in the literature) has been developed in order to take into
      consideration both the time-dependency of the risk factor (e.g., nosocomial
      infections) and the presence of competing risks (e.g., death and discharge) at
      each time point. However, this approach does not take into account the possible
      heterogeneity of the study population. In this paper, we investigate an extension
      of this model and suggest an adjusted disability multistate model including
      covariates in each transition. This new multistate model has led us to define the
      concepts of overall and profiled attributable risk. We use a classical
      semiparametric approach to estimate the model and the new attributable risk. A
      simulation study is investigated and we show, in particular, that neglecting the
      presence of covariates when estimating the model can lead to an important bias.
      The methodology developed in this paper is applied to data on ventilator
      associated pneumonia in 12 French intensive care units.

PMID- 22847863
TI  - Temporary vocal fold immobility after chemocauterization of the pyriform sinus
      fistula opening with trichloroacetic acid.
AB  - Pyriform sinus fistula (PSF) is a rare branchial pouch anomaly. Circumferential
      chemocauterization of the opening with trichloroacetic acid (TCA) is a simple,
      reliable treatment of choice with little morbidity. However, we experienced two
      cases of vocal fold immobility after chemocauterization of the PSF opening with
      TCA. Vocal fold mobility recovered spontaneously within 8 weeks in both cases.
      Herein, we report these cases in addition to a review of the literature.

PMID- 22847864
TI  - [Co(eta5-P5){eta2-P2H(mes)}]2-: a phospha-organometallic complex obtained by the
      transition-metal-mediated activation of the heptaphosphide trianion.
AB  - A carbon copy: The chemical activation of the heptaphosphide trianion with
      [Co(PEt(2)Ph)(2)(mes)(2)] (see picture; 1) yields the novel phospha
      organometallic complex [Co(eta(5)-P(5)){eta(2)-P(2)H(mes)}](2-) (2). The reaction
      product maintains the nuclearity of the parent cluster, but extensive cage
      fragmentation takes place to yield a diamagnetic "inorganometallic" cobalt
      complex.

PMID- 22847865
TI  - The ethics of living donation for liver transplant: beyond donor autonomy.
AB  - This paper will present and discuss our conclusions about the ethics of living
      donation for liver transplant (LDLT) after 8 year of collaboration between our
      clinical ethics consultation service and liver transplant teams, in the course of
      which we met with all donor-candidates. We will focus on the results of a follow
      up study that was conducted in order to evaluate the long-term consequences for
      potential donors and to interview them on the ethical aspects of the screening
      process. This study was conducted from April 2007 to November 2009 and consisted
      of interviews with donor-candidates, regardless of whether they underwent harvest
      surgery, at least 1 year after the recipient's transplant. We explored their
      views about their own and the recipients' physical and psychological condition,
      changes in family and career dynamics, their experience as potential or real
      donors, and their views about LDLT process in general. Results shed new light on
      the ethical grounds of LDLT and allow us to envisage new ways of improving the
      ethical soundness of current procedures and practices. In particular, we argue
      that the purpose of an ethics committee should be to provide follow-up support
      for the donors rather than merely to check the freedom of donors' consent. We
      also suggest that the recipient's consent deserves more attention than it
      currently receives.

PMID- 22847866
TI  - What determines motor neuron number? Slow scaling of facial motor neuron numbers
      with body mass in marsupials and primates.
AB  - How does the number of motor neurons in the brain correlate with the muscle mass
      to be controlled in the body? Numbers of motor neurons are known to be adjusted
      during development by cell death, but the change in the percentage of surviving
      motor neurons in response to experimental changes in target muscle mass is
      relatively small. Here we address the quantitative matching between final numbers
      of motor neurons in the facial nucleus and body mass (which we use as a proxy for
      the muscle mass). In 22 marsupial species, we found that the number of facial
      motor neurons is strongly correlated with body mass, and scales across species as
      a power function of body mass with a very small exponent of 0.184, which is close
      to the exponent found in primates from previously published data. With such an
      exponent, doubling the body mass is accompanied by a modest increase of only 14%
      in numbers of facial motor neurons, while halving body mass results in a decrease
      of only 12%. These numbers are remarkably similar to the 15-20% increase or 8%
      decrease in the number of spinal cord motor neurons that results from
      experimental or natural doubling or reducing by half the target muscle field of
      birds and amphibians. The scaling rule presented here might thus account for the
      quantitative matching of motor neurons to their target muscle mass in evolution.
      With this small scaling exponent, our data also raise the possibility that larger
      animals will have larger motor units.

PMID- 22847867
TI  - Radionuclide concentrations in air particulate at Palermo (Italy) following
      Fukushima accident.
AB  - Following the Fukushima accident, a series of samplings were carried out with a
      daily frequency to detect the arrival of radioactive contamination in air at
      Palermo (Italy) and to follow its evolution during the time. Air particulate
      collection was performed by suction of atmospheric air through cellulose filter
      paper by means of a high-volume air sampler (~15 000 m(3) d(-1)). Spectrometric
      analysis of the filters highlights the presence of (131)I, (134)Cs, (137)Cs and,
      only for a few samples, traces of (132)Te-(132)I and (136)Cs. Maximum airborne
      concentrations were 883 MUBq m(-3) for (131)I (only particulate), 81 MUBq m(-3)
      for (137)Cs and 70 MUBq m(-3) for (134)Cs. From a dose to population point of
      view, no significant values were obtained. The concentration values are from 1000
      to 100 000 times lower than the ones measured after the Chernobyl accident,
      while, for only (137)Cs, are comparable with the ones highlighted after the
      Algeciras accident (Spain, 1998).

PMID- 22847868
TI  - Determination of environmental radioactivity (238U, 232Th and 40K) and indoor
      natural background radiation level in Chennai city (Tamilnadu State), India.
AB  - An extensive study on the determination of the natural radioactivity ((238)U,
      (232)Th and (40)K) levels in soil samples of Chennai city, India has been
      undertaken and the results of the same are compared with the levels reported in
      other Indian cities as well as other parts of the world. The radioactivity
      content in the soil samples, the absorbed dose rate, annual effective dose
      equivalent, radium equivalent activity, internal and external hazard indices were
      calculated and compared with UNSCEAR 2000 recommended values. In addition to the
      above, mapping of indoor natural background gamma radiation levels has been made
      using thermo luminescent dosemeters throughout Chennai city and the same are
      reported.

PMID- 22847869
TI  - Genotype-phenotype analysis of 4q deletion syndrome: proposal of a critical
      region.
AB  - Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an
      estimated incidence of 1 in 100,000. Although variable, the clinical spectrum
      commonly includes craniofacial, developmental, digital, skeletal, and cardiac
      involvement. Data on the genotype-phenotype correlation within the 4q arm are
      limited. We present detailed clinical and genetic information by array CGH on 20
      patients with 4q deletions. We identified a patient who has a ~465 kb deletion
      (186,770,069-187,234,800, hg18 coordinates) in 4q35.1 with all clinical features
      for 4q deletion syndrome except for developmental delay, suggesting that this is
      a critical region for this condition and a specific gene responsible for
      orofacial clefts and congenital heart defects resides in this region. Since the
      patients with terminal deletions all had cleft palate, our results provide
      further evidence that a gene associated with clefts is located on the terminal
      segment of 4q. By comparing and contrasting our patients' genetic information and
      clinical features, we found significant genotype-phenotype correlations at a
      single gene level linking specific phenotypes to individual genes. Based on these
      data, we constructed a hypothetical partial phenotype-genotype map for chromosome
      4q which includes BMP3, SEC31A, MAPK10, SPARCL1, DMP1, IBSP, PKD2, GRID2, PITX2,
      NEUROG2, ANK2, FGF2, HAND2, and DUX4 genes.

PMID- 22847870
TI  - Complete (1) H and (13) C NMR spectral assignments for the glycoalkaloid
      dehydrocommersonine.
AB  - The normal levels and types of glycoalkaloids found in commercial varieties of
      potato (Solanum tuberosum) appear to present no hazard to human health. However
      when wild Solanum species are used in breeding endeavors, new and untested
      glycoalkaloids may be introduced. Recent studies of domestic crosses with a wild
      Solanum oplocense accession indicated that the levels of a non-indigenous
      glycoalkaloid appeared associated with reduced defoliation by the Colorado potato
      beetle. The non-indigenous glycoalkaloid was isolated from foliage of the wild S.
      oplocense accession and unambiguously characterized by high-resolution
      electrospray ionization mass spectrometry and NM analysis as the glycoalkaloid
      dehydrocommersonine.

PMID- 22847871
TI  - Maternal factors associated with misperceptions of the second-trimester sonogram.
AB  - OBJECTIVE: Prior studies have shown that patients have poor understanding of
      prenatal screening tests. The purpose of this study was to evaluate the frequency
      with which patients have poor understanding of the sensitivity and safety of the
      second-trimester fetal sonogram and to identify maternal factors associated with
      poor understanding. METHOD: One hundred fifty-five women presenting for a routine
      fetal anatomy scan completed a survey that assessed their understanding of the
      diagnostic sensitivity and safety of ultrasound, their demographic
      characteristics, and the sources of information of their knowledge of ultrasound.
      The frequency of misperception with regard to sonographic sensitivity or safety
      was determined, and both univariable and multivariable analyses were performed to
      identify factors associated with misperception. RESULTS: Fifty-one percent of
      women had a misperception of the sensitivity or safety of a second-trimester
      sonogram. Although multiple characteristics (age, ethnicity, education, income,
      source of ultrasound information) were associated with this misperception in
      univariable analysis, only education and income remained independently associated
      with misperception in multivariable regression. CONCLUSION: Lower educational
      attainment and lower income are associated with misperception of the sensitivity
      and safety of a second-trimester sonogram.

PMID- 22847872
TI  - Auditory expectation: the information dynamics of music perception and cognition.
AB  - Following in a psychological and musicological tradition beginning with Leonard
      Meyer, and continuing through David Huron, we present a functional, cognitive
      account of the phenomenon of expectation in music, grounded in computational,
      probabilistic modeling. We summarize a range of evidence for this approach, from
      psychology, neuroscience, musicology, linguistics, and creativity studies, and
      argue that simulating expectation is an important part of understanding a broad
      range of human faculties, in music and beyond.

PMID- 22847874
TI  - Hydride ligands make the difference: density functional study of the mechanism of
      the Murai reaction catalyzed by [Ru(H)2(H2)2(PR3)2] (R=cyclohexyl).
AB  - The catalytic cycle for the Murai reaction at room temperature between ethylene
      and acetophenone catalyzed by [Ru(H)(2)(H(2))(2)(PMe(3))(2)] has been studied
      computationally at the B3PW91 level. The active species is the ruthenium
      dihydride complex [Ru(H)(2)(PMe(3))(2)]. Coordination of the ketone group to Ru
      induces very easy C-H bond cleavage. Coordination of ethylene after ketone de
      coordination, followed by ethylene insertion into a Ru-H bond, creates the Ru
      ethyl bond. Isomerization of the complex to a Ru(IV) intermediate creates the
      geometry adapted to C-C bond formation. Re-coordination of the ketone before the
      C-C coupling lowers the energy of the corresponding TS. The highest point on the
      potential energy surface (PES) is the TS for the isomerization to the Ru(IV)
      intermediate, which prepares the catalyst geometry for the C-C coupling step.
      Inclusion of dispersion corrections significantly lowers the height of the
      overall activation barrier. The actual bond cleavage and bond forming processes
      are associated to low activation barriers because of the presence of hydrogen
      atoms around the Ru center. They act as redox buffers through formation and
      breaking of H-H bonds in the coordination sphere. This flexibility allows optimal
      repartition of the various ligands according to the change in stereoelectronic
      demands along the catalytic cycle.

PMID- 22847873
TI  - Assessment of modified gold surfaced titanium implants on skeletal fixation.
AB  - Noncemented implants are the primary choice for younger patients undergoing total
      hip replacements. However, the major concern in this group of patients regarding
      revision is the concern from wear particles, periimplant inflammation, and
      subsequently aseptic implant loosening. Macrophages have been shown to liberate
      gold ions through the process termed dissolucytosis. Furthermore, gold ions are
      known to act in an anti-inflammatory manner by inhibiting cellular NF-kappaB-DNA
      binding. The present study investigated whether partial coating of titanium
      implants could augment early osseointegration and increase mechanical fixation.
      Cylindrical porous coated Ti-6Al-4V implants partially coated with metallic gold
      were inserted in the proximal region of the humerus in ten canines and control
      implants without gold were inserted in contralateral humerus. Observation time
      was 4 weeks. Biomechanical push out tests and stereological histomorphometrical
      analyses showed no statistically significant differences in the two groups. The
      unchanged parameters are considered an improvement of the coating properties, as
      a previous complete gold-coated implant showed inferior mechanical fixation and
      reduced osseointegration compared to control titanium implants in a similar
      model. Since sufficient early mechanical fixation is achieved with this new
      coating, it is reasonable to investigate the implant further in long-term
      studies.

PMID- 22847875
TI  - Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve
      fiber damage.
AB  - Bilirubin can cause temporary or permanent sensorineural deafness in newborn
      babies with hyperbilirubinemia. However, the underlying targets and physiological
      effects of bilirubin-induced damage in the peripheral auditory system are
      unclear. Using cochlear functional assays and electron microscopy imaging of the
      inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted
      in threshold elevation in both compound action potential (CAP) and auditory
      brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug
      administration. The threshold elevation was associated with delayed wave
      latencies and elongated interwave intervals in ABR and CAP. At 72 hr
      postinjection, these measures returned to control levels, except for the CAP
      amplitude. Cochlear microphonics remained unchanged during the experiment.
      Morphological abnormalities were consistent with the electrophysiological
      dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn,
      myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of
      type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair
      cells at 8 hr posttreatment. Similar to the electrophysiological findings,
      morphological changes were mostly reversed 10 days after treatment, except for
      the ANF reduction in the basal turn. These results suggest that
      hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral
      neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of
      SGNs and their fibers. Our observations indicate a potential connection between
      hyperbilirubinemia and auditory neuropathy.

PMID- 22847876
TI  - Quantum dot nanoparticles affect the reproductive system of Caenorhabditis
      elegans.
AB  - Quantum dots (QDs) are an increasingly important class of nanoparticle, but
      little ecotoxicological data for QDs has been published to date. The effects of
      mercaptosuccinic acid (MSA)-capped QDs (QDs-MSA) and equivalent concentrations of
      cadmium (Cd) from cadmium chloride on growth and reproduction of the nematode
      Caenorhabditis elegans (Rhabditidae) were assessed in laboratory experiments.
      Growth from larvae to adults of C. elegans was unaffected by exposure to 1 uM
      fluorescent QDs-MSA, but adults produced more embryos and laid them prematurely.
      Furthermore, C. elegans exposed to QDs-MSA (1 uM) showed a high percentage of
      embryo mortality (19.2 +/- 0.5, p < 0.001, percentage +/- standard deviation)
      compared with unexposed nematodes (11.6 +/- 0.4). An egg-laying defect phenotype
      was also observed at high frequency in response to 1 uM QDs-MSA exposure (38.3 +/
      3.6%, p < 0.01; control 10.0 +/- 2.2%). This resulted in a reduced mean life
      span (20.5 +/- 1.1 d, p < 0.05) compared with the control (24.6 +/- 1.0 d).
      Cadmium also caused reduced life span in C. elegans, but a low incidence of egg
      laying defects was observed, suggesting that Cd and QDs-MSA affected C. elegans
      by different mechanisms. Furthermore, egg-laying defects caused by QDs-MSA
      responded to the addition of the anticonvulsant ethosuximide and to a lesser
      extent to the neurotransmitter serotonin, suggesting that QDs-MSA might have
      disrupted motor neurons during the reproduction process.

PMID- 22847877
TI  - Juvenile recurrent respiratory papilloma: variable intersurgical intervals.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the patterns of surgical frequency in pediatric
      patients undergoing surgery with CO(2)  laser ablation for juvenile onset
      recurrent respiratory papillomatosis (JORRP). The hypothesis is that over time
      there is a high variability in surgical frequency independent of the use of an
      adjuvant therapy. STUDY DESIGN: Retrospective case review. METHODS: All pediatric
      patients treated surgically with the CO(2)  laser for JORRP by two senior
      surgeons at a tertiary pediatric hospital over an 11-year period were evaluated.
      Regression analysis was performed. An online survey was conducted of the American
      Academy of Pediatric Otolaryngology membership on their practice patterns
      regarding JORRP. RESULTS: Twenty-nine patients were identified, and of those, 20
      were included in regression analysis. Several distinct patterns were noted. Only
      five of the 20 patients (25%) had a constant rate of procedures throughout the
      observation period. Three (15%) of the patients had continual decrease and one
      (5%) of the patients had a continual increase in the surgical rate throughout the
      study period. Eleven (55%) had a fluctuation in the pattern of their recurrences.
      When queried on how they approach when to repeat intervention for JORRP patients,
      more than 16 responses were given, and the most common determinants included
      standard set interval, previous operative findings, and previous interval.
      CONCLUSIONS: The natural fluctuation in intersurgical intervals without the use
      of any adjuvant therapy confounds the use of intersurgical interval as an outcome
      measure for the success of adjuvant therapy. Accelerations and decelerations were
      noted but cannot be explained.

PMID- 22847878
TI  - On the dynamics of liquids in their viscous regime approaching the glass
      transition.
AB  - Recently, Mallamace et al. (Eur. Phys. J. E 34, 94 (2011)) proposed a crossover
      temperature, T(*), and claimed that the dynamics of many supercooled liquids
      follow an Arrhenius-type temperature dependence between T(*) and the glass
      transition temperature T(g). The opposite, namely super-Arrhenius behavior in
      this viscous regime, has been demonstrated repeatedly for molecular glass-former,
      for polymers, and for the majority of the exhaustively studied inorganic glasses
      of technological interest. Therefore, we subject the molecular systems of the
      Mallamace et al. study to a "residuals" analysis and include not only viscosity
      data but also the more precise data available from dielectric relaxation
      experiments over the same temperature range. Although many viscosity data sets
      are inconclusive due to their noise level, we find that Arrhenius behavior is not
      a general feature of viscosity in the T(g) to T(*) range. Moreover, the residuals
      of dielectric relaxation times with respect to an Arrhenius law clearly reveal
      systematic curvature consistent with super-Arrhenius behavior being an endemic
      feature of transport properties in this viscous regime. We also observe a common
      pattern of how dielectric relaxation times decouple slightly from viscosity.

PMID- 22847880
TI  - Does hearing lead to understanding? Theory of mind in toddlers and preschoolers
      with cochlear implants.
AB  - OBJECTIVE: Theory of Mind (ToM) refers to the ability to understand the
      subjectivity of people's intentions, desires, and beliefs. Research shows that
      ToM in deaf children is delayed, yet the few studies that examined ToM in deaf
      children with a cochlear implant (CI) report contradictory results. This study
      examined multiple aspects of ToM in early-implanted children. METHODS: 3
      intention tasks were administered to 72 children with CI and 69 normal-hearing
      children (age, 12-60 months). Furthermore, 3 desire and belief tasks were
      administered to a subsample of children aged 30 months or over. RESULTS: Children
      with CI showed intention-understanding skills equal to normal-hearing children,
      but lagged behind on desire and belief understanding, even after excluding
      children with language delays. CONCLUSIONS: Children with CI appear to master the
      initial stages of ToM development, but fall behind on more advanced ToM
      abilities. Yet, both groups showed similar patterns of development.

PMID- 22847881
TI  - Introduction to special section: advancing research on the intersection of
      families, culture, and health outcomes.

PMID- 22847882
TI  - Commentary for pioneers in pediatric psychology: thirty-seven years of research,
      training, and clinical practice in pediatric psychology.

PMID- 22847883
TI  - Mesh in prolapse surgery: an imaging perspective.

PMID- 22847884
TI  - [Mastoid obliteration with a highly porous bone grafting material in combination
      with cartilage].
AB  - BACKGROUND: An open mastoid cavity might lead to various problems for the
      patient. Chronic inflammation of the cavity with secretion, changes in the
      acoustic behavior, vertigo in restricted situations and an impaired self-cleaning
      function might affect the patient. For surgical treatment reducing of the size of
      such cavities have been described. Besides autologous materials such as
      hydroxyapatite or alloplastic substances as tricalcium phosphate have been
      previously used. A very slow resorption of these materials with rejection has
      been described. The new ceramic NanoBone(r) was fabricated in a sol-gel process
      at 700  degrees C depositing unsintered hydroxylapatite in a SiO2 structure. This
      method provides a nano/microstructure of high porosity of the resulting matrix.
      MATERIAL AND METHODS: 20 patients were reexamined after an average of 2 years and
      5 months after obliteration of the open mastoid cavity with NanoBone(r). We
      compared pre- and postoperative findings in terms of otorrhea, frequency of
      medical consultation, vertigo and otoscopic findings. In 5 patients, in addition,
      a postoperative CT scan of the temporal bones was used for evaluation of
      osteoinduction and osteointegration. RESULTS: After obliteration of the open
      mastoid cavity with NanoBone (r) we observed an uneventfully healing. After
      surgery we achieved a reduction of vertigo, otorrhea and frequency of medical
      consultations for the single patient. CONCLUSION: The obliteration of an open
      mastoid cavity with NanoBone (r) is a safe alternative method relative to the
      surgical techniques with autologous materials.

PMID- 22847885
TI  - HYSCORE and Davies ENDOR study of irradiated ultra high molecular weight
      polyethylene.
AB  - Ultra high molecular weight polyethylene (UHMWPE) has been studied with different
      magnetic resonance techniques to elicit information on the nature and the
      location of radicals generated during high energy irradiation. Field swept
      electron paramagnetic resonance, pulsed Davies electron nuclear double resonance
      and hyperfine sublevel correlation spectroscopic measurements allowed extracting
      for the first time the full (1) H hyperfine coupling tensors of the most abundant
      radical, i.e. a secondary alkyl radical and to ascertain the formation of allyl
      radicals in the first stages of the irradiation process. The (1) H hyperfine
      coupling tensors are analogous to those reported for single crystal irradiated
      polyethylene, suggesting that radicals generated in UHMWPE are located in the
      crystalline region of the polymer.

PMID- 22847886
TI  - Highly enantioselective hetero-Diels-Alder reaction of 1,3-bis(silyloxy)-1,3
      dienes with aldehydes catalyzed by chiral disulfonimide.

PMID- 22847887
TI  - Rho-kinase-dependent pathway mediates the hepatoprotective effects of sorafenib
      against ischemia/reperfusion liver injury in rats with nonalcoholic
      steatohepatitis.
AB  - During liver transplantation, nonalcoholic steatohepatitis (NASH) aggravates
      ischemia/reperfusion (IR) injury by activating various kinases and subsequently
      releasing cytokines and chemokines. Nonetheless, the effect of the multikinase
      inhibitor sorafenib on IR liver injury in rats with NASH has never been explored.
      Our study was designed to determine this effect and associated mechanisms in NASH
      rats. Sorafenib was acutely administered to NASH rats with IR liver injury that
      were or were not chronically pretreated with the Rho-kinase-specific inhibitor
      fasudil. Then, the following were evaluated: mean arterial pressure; hepatic
      blood flow and microcirculatory dysfunction; hepatic inflammation (serum alanine
      aminotransferase); necrosis; apoptosis; leukocyte infiltration; CD45 staining;
      caspase levels and DNA fragmentation; various serum and hepatic cytokines; and
      proteins and genes of the Raf/mitogen-activated protein-extracellular signal
      regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK), p38
      mitogen-activated protein kinase, and apoptosis pathways. In NASH rats with IR
      liver injury, hepatic inflammation, necrosis, apoptosis, leukocyte infiltration,
      and microcirculatory dysfunction were significantly attenuated by the acute
      administration of sorafenib through the inhibition of the hepatic release of
      macrophage inflammatory protein 2, keratinocyte chemoattractant, granulocyte
      monocyte colony-stimulating factor, and hepatic caspase-3 and caspase-9 as well
      as DNA fragmentation. Furthermore, there was decreased expression of p-Raf1
      (where p indicates the phosphorylated form), p-MEK1/2, p-ERK1/2, p-Rho-kinase, B
      cell lymphoma 2-associated death promoter, and B cell lymphoma 2-associated X
      protein at the protein and messenger RNA levels. Notably, the aforementioned
      beneficial effects of sorafenib were significantly abolished by chronic
      pretreatment with the Rho-kinase-specific inhibitor fasudil. This study
      demonstrated that the multikinase inhibitor sorafenib protects NASH rats from IR
      injury by interfering with the inflammation, necrotic, and apoptotic responses
      causing leukocyte-dependent hepatic microcirculatory dysfunction. The
      hepatoprotective effects of sorafenib seem to work through the inhibition of the
      Rho-kinase-dependent Raf/MEK/ERK pathway, which is up-regulated during IR injury
      in the livers of NASH rats.

PMID- 22847888
TI  - Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: a
      meta-analysis based on 17 case-control studies.
AB  - Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate
      metabolism, is thought to be involved in the development of nonsyndromic
      orofacial clefts (NSOC). However, conflicting results have been achieved when
      evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms
      and the risk of NSOC. To obtain more precise estimations of these associations, a
      meta-analysis recruiting 17 case-control studies was performed. Among Asians we
      found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T
      variant could contribute to elevated risks of NSOC, compared with CC wild-type
      homozygote (OR=1.741, 95% CI=1.043-2.907 for CT vs. CC, OR=2.311, 95% CI=1.313
      4.041 for TT vs. CC, and OR=1.740, 95% CI=1.051-2.882 for CT/TT vs. CC,
      respectively). Similar effect was also observed on MTHFR 677T T allele, when
      using C allele as a reference in Asians (OR=1.420, 95% CI=1.191-1.693, for T
      allele vs. C allele). Furthermore, in stratified analysis by types of disease,
      CT/CC was suggested to confer decreased susceptibility to CL/P under recessive
      genetic model (OR=0.854, 95% CI=0.730-1.000). For MTHFR A1298C, the MTHFR 1298C
      allele in the case group of Caucasians was significantly lower than that in the
      control group, suggesting a protective effect against NSOC in Caucasian
      populations (OR=0.711, 95% CI=0.641-0.790, for C allele vs. A allele). In
      conclusion, the meta-analysis provided confirmative evidences that infants' MTHFR
      C677T and A1298C polymorphisms were involved in the development of NSOC.

PMID- 22847889
TI  - The location of the major ascending and descending spinal cord tracts in all
      spinal cord segments in the mouse: actual and extrapolated.
AB  - Information on the location of the major spinal cord tracts in the mouse is
      sparse. We have collected published data on the position of these tracts in the
      mouse and have used data from other mammals to identify the most likely position
      of tracts for which there is no mouse data. We have plotted the position of six
      descending tracts (corticospinal, rubrospinal, medial and lateral
      vestibulospinal, rostral and caudal reticulospinal) and eight ascending tracts
      (gracile; cuneate; postsynaptic dorsal columns; dorsolateral, lateral, and
      anterior spinothalamic; dorsal and ventral spinocerebellar) on diagrams of
      transverse sections of all mouse spinal cord segments from the first cervical to
      the third coccygeal segment.

PMID- 22847890
TI  - Prostate cancer is known by the companionship with ATM and miRNA it keeps:
      craftsmen of translation have dual behaviour with tailors of life thread.
AB  - Research on prostate cancer progression has focused extensively on the concept of
      miRNA, which can operate either as promoters or as suppressors of carcinogenesis.
      Moreover, recent genetic studies and emerging functional work show that
      strikingly similar and overlapping pathways are involved in prostate
      carcinogenesis. Unswervingly, these elements constitute a recently explored
      'network of networks' that dynamically reorganizes during DNA damage and is
      responsible for positively or negatively regulating genome organization and
      integrity. We consider these facets of convergence and discuss how insights from
      diametrically opposed interactions of ataxia-telangiectasia mutated and mitrons
      can inform us about, and possibly help us to get a step closer to personalized
      medicine.

PMID- 22847891
TI  - Feed-forward hierarchical model of the ventral visual stream applied to
      functional brain image classification.
AB  - Functional brain imaging is a common tool in monitoring the progression of
      neurodegenerative and neurological disorders. Identifying functional brain
      imaging derived features that can accurately detect neurological disease is of
      primary importance to the medical community. Research in computer vision
      techniques to identify objects in photographs have reported high accuracies in
      that domain, but their direct applicability to identifying disease in functional
      imaging is still under investigation in the medical community. In particular,
      Serre et al. (: In: IEEE Conference on Computer Vision and Pattern Recognition
      (CVPR-05). pp 994-1000) introduced a biophysically inspired filtering method
      emulating visual processing in striate cortex which they applied to perform
      object recognition in photographs. In this work, the model described by Serre et
      al. [2005] is extended to three-dimensional volumetric images to perform signal
      detection in functional brain imaging (PET, SPECT). The filter outputs are used
      to train both neural network and logistic regression classifiers and tested on
      two distinct datasets: ADNI Alzheimer's disease 2-deoxy-D-glucose (FDG) PET and
      National Football League players Tc99m HMPAO SPECT. The filtering pipeline is
      analyzed to identify which steps are most important for classification accuracy.
      Our results compare favorably with other published classification results and
      outperform those of a blinded expert human rater, suggesting the utility of this
      approach.

PMID- 22847893
TI  - (1) H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus
      monkeys with morphine treatment and withdrawal intervention.
AB  - Comprehensive cerebral metabolites involved in morphine dependence have not been
      well explored. To gain a better understanding of morphine dependence and
      withdrawal therapy in a model highly related to humans, metabolic changes in
      brain hippocampus and prefrontal cortex (PFC) of rhesus monkeys were measured by
      (1) H-nuclear magnetic resonance spectroscopy, coupled with partial least squares
      and orthogonal signal correction analysis. The results showed that concentrations
      of myoinositol (M-Ins) and taurine were significantly reduced, whereas lactic
      acid was increased in hippocampus and PFC of morphine-dependent monkeys.
      Phosphocholine and creatine increased in PFC but decreased in hippocampus after
      chronic treatment of morphine. Moreover, N-acetyl aspartate (NAA), gamma
      aminobutyric acid, glutamate, glutathione, methionine, and homocysteic acid also
      changed in these brain regions. These results suggest that chronic morphine
      exposure causes profound disturbances of neurotransmitters, membrane, and energy
      metabolism in the brain. Notably, morphine-induced dysregulations in NAA,
      creatine, lactic acid, taurine, M-Ins, and phosphocholine were clearly reversed
      after intervention with methadone or clonidine. Our study highlights the
      potential of metabolic profiling to enhance our understanding of metabolite
      alteration and neurobiological actions associated with morphine addiction and
      withdrawal therapy in primates.

PMID- 22847894
TI  - Tensorial elastic network model for protein dynamics: integration of the
      anisotropic network model with bond-bending and twist elasticities.
AB  - We present a tensorial elastic network model (TNM) to describe the equilibrium
      fluctuations of proteins near their native fold structure. The model combines the
      anisotropic network model (ANM), bond bending elasticity, and backbone twist
      elasticity, and can predict both the isotropic fluctuations, similar to the
      Gaussian network model (GNM), and anisotropic fluctuations, similar to the ANM.
      TNM performs equally well for B-factor predictions as GNM and predicts the
      anisotropy of B-factors better than ANM. The model also outperforms the ANM in
      its predictability of the complete anisotropic displacement parameters.

PMID- 22847892
TI  - Correlating macrophage morphology and cytokine production resulting from
      biomaterial contact.
AB  - The morphological and inflammatory responses of adherent macrophages are
      correlated to evaluate the biocompatibility of surfaces. Monocyte-derived
      macrophage (MDM), THP-1, and THP-1 cells expressing GFP-actin chimeric protein
      were seeded onto glass, polyurethane (PU), and glass surface modified with
      quaternary ammonium salt functionalized chitosan (CH-Q) and hyaluronic acid (HA).
      Using confocal microscopy, the surface area, volume and 3D shape factor of
      adherent macrophages was quantified. For comparison, functional consequences of
      cell-surface interactions that activate macrophages and thereby elicit secretion
      of a proinflammatory cytokine were evaluated. Using an enzyme linked immune
      sorbent assay, tumor necrosis factor-alpha (TNF-alpha) was measured. On glass,
      macrophages exhibited mainly an amoeboid shape, exhibited the largest surface
      area, volume, and 3D shape factor and produced the most TNF-alpha. On PU,
      macrophages displayed mainly a hemispherical shape, exhibited an intermediate
      volume, surface area and 3D shape factor, and produced moderate TNF-alpha. In
      contrast, on CH-Q and HA surfaces, macrophages were spherical, exhibited the
      smallest volume, surface area, and 3D shape factor, and produced the least TNF
      alpha. These studies begin to validate the use of GFP-actin-modified MDM as a
      novel tool to correlate cell morphology with inflammatory cell response.

PMID- 22847895
TI  - Evaluation of liver fibrosis by investigation of hepatic parenchymal perfusion
      using contrast-enhanced ultrasound: an animal study.
AB  - PURPOSE: To investigate the value of assessing the hepatic parenchymal perfusion
      in contrast-enhanced ultrasound (CEUS) for evaluating liver fibrosis, using an
      animal model. METHODS: Seventy Sprague-Dawley rats were divided into experimental
      (n = 35) and control (n = 35) groups. In the experimental group, liver fibrosis
      was induced by intraperitoneal injection of carbon tetrachloride. CEUS of the
      liver was performed at a 2-week interval for 14 weeks. Signal intensity of liver
      parenchyma was analyzed with time-intensity curves. Histologic examination of
      liver specimens of the animals was performed to assess the fibrosis stage.
      RESULTS: The peak signal intensity of hepatic parenchymal perfusion in stage 2-3
      fibrosis was significantly lower than that in stage 0-1. The time to peak
      intensity of hepatic parenchymal perfusion was significantly longer in the
      experimental group than the control group, and in the stage 3 fibrosis than in
      stages 0-2 fibrosis. Using time to peak intensity of hepatic parenchymal
      perfusion to distinguish stage 3 fibrosis and stages 0-2 fibrosis, the optimum
      cutoff was 75,000 milliseconds with the sensitivity and specificity of 67% and
      78%, respectively. CONCLUSIONS: This animal study showed that CEUS has the
      potential to be a complementary imaging tool in the evaluation of liver fibrosis.

PMID- 22847896
TI  - The AdVance male sling as a minimally invasive treatment for intrinsic sphincter
      deficiency in patients with neurogenic bladder sphincter dysfunction: a pilot
      study.
AB  - AIMS: The aim of the study was to evaluate feasibility, efficacy, and safety of
      the AdVance male sling in neuropathic male patients with intrinsic sphincter
      deficiency. METHODS: We evaluated 20 consecutive male neuropathic patients (12
      menigomyelocele and 8 lower spinal cord injured), age 23 +/- 13 years (range 6-52
      years) with urodynamically proven sphincter deficiency and stress urinary
      incontinence. In all patients an AdVance male sling was implanted from June 2007
      to September 2009. Patients were evaluated with the number of pads per day (PPD),
      visual analogue scale (VAS) for continence and the International Consultation on
      Incontinence-Short Form (ICIQ-SF). Cure was defined as a 10 on VAS or using no
      pads for urinary leakage, improvement as >5 and failure as <=5. RESULTS: Positive
      effect in 13 of 20 patients (65%) at 1-year follow-up: 8 patients were cured, 5
      improved, and 7 failed. VAS score increased from baseline 2.6 (SD 2.0) to 7.2 (SD
      3.5) at 12 months (P < 0.001). ICIQ-SF decreased from 14 (SD 4.2) to 4 (SD 4.1)
      (P < 0.001). Friedman and Wilcoxon tests revealed at 1, 3, 6, 9, and 12 months
      significant improvement compared to baseline (P = 0.008). CONCLUSIONS:
      Implantation of the AdVance male sling is feasible in both adult and pediatric
      patients. A promising cure/improvement rate was achieved as well as a low
      complication rate.

PMID- 22847897
TI  - Dioxygen reactivity of biomimetic iron-catecholate and iron-o-aminophenolate
      complexes of a tris(2-pyridylthio)methanido ligand: aromatic C-C bond cleavage of
      catecholate versus o-iminobenzosemiquinonate radical formation.
AB  - An iron(III)-catecholate complex [L(1)Fe(III)(DBC)] (2) and an iron(II)-o
      aminophenolate complex [L(1)Fe(II)(HAP)] (3; where L(1) = tris(2
      pyridylthio)methanido anion, DBC = dianionic 3,5-di-tert-butylcatecholate, and
      HAP = monoanionic 4,6-di-tert-butyl-2-aminophenolate) have been synthesised from
      an iron(II)-acetonitrile complex [L(1)Fe(II)(CH(3)CN)(2)](ClO(4)) (1). Complex 2
      reacts with dioxygen to oxidatively cleave the aromatic C-C bond of DBC giving
      rise to selective extradiol cleavage products. Controlled chemical or
      electrochemical oxidation of 2, on the other hand, forms an iron(III)-semiquinone
      radical complex [L(1)Fe(III)(SQ)](PF(6)) (2(ox)-PF(6); SQ = 3,5-di-tert
      butylsemiquinonate). The iron(II)-o-aminophenolate complex (3) reacts with
      dioxygen to afford an iron(III)-o-iminosemiquinonato radical complex
      [L(1)Fe(III)(ISQ)](ClO(4))(3(ox)-ClO(4); ISQ = 4,6-di-tert-butyl-o
      iminobenzosemiquinonato radical) via an iron(III)-o-amidophenolate intermediate
      species. Structural characterisations of 1, 2, 2(ox) and 3(ox) reveal the
      presence of a strong iron-carbon bonding interaction in all the complexes. The
      bond parameters of 2(ox) and 3(ox) clearly establish the radical nature of
      catecholate- and o-aminophenolate-derived ligand, respectively. The effect of
      iron-carbon bonding interaction on the dioxygen reactivity of biomimetic iron
      catecholate and iron-o-aminophenolate complexes is discussed.

PMID- 22847898
TI  - Recipient outcomes of salvage liver transplantation versus primary liver
      transplantation: a systematic review and meta-analysis.
AB  - Salvage liver transplantation (SLT), or liver transplantation after liver
      resection (LR), has been performed after primary LR for many years. However, the
      true outcomes and risks of SLT versus primary liver transplantation (PLT) remain
      unclear. We performed a systematic review and meta-analysis to evaluate the
      survival rate of SLT recipients and the incidence of postoperative complications.
      Among 2799 screened references, 7 eligible studies were identified. The results
      of the meta-analysis indicated no statistically significant differences in the
      overall survival rates of SLT and PLT: the pooled relative risk (RR) was 0.99
      [95% confidence interval (CI) = 0.90-1.09, P = 0.87] at 1 year, 0.97 (95% CI =
      0.83-1.13, P = 0.68) at 3 years, and 0.96 (95% CI = 0.81-1.13, P = 0.61) at 5
      years. As for postoperative complications, there were no statistically
      significant differences in the incidence of sepsis and biliary complications
      between SLT and PLT, but there was a significantly higher incidence of bleeding
      with SLT (RR = 2.84, 95% CI = 1.57-5.13, P = 0.001). In conclusion, the overall
      survival associated with SLT is similar to that associated with PLT. Because of
      the limited organ donor pool, SLT might be an acceptable therapy for patients
      undergoing primary LR for hepatocellular carcinoma.

PMID- 22847899
TI  - Enantioselective synthesis of tertiary alpha-hydroxy phosphonates catalyzed by
      carbohydrate/cinchona alkaloid thiourea organocatalysts.

PMID- 22847901
TI  - Sequence position and side chain length dependence of charge pair interactions in
      collagen triple helices.
AB  - In this study, we examine eight ABC heterotrimers whose self-assembly is directed
      through electrostatic interactions. Oppositely charged pairs of amino acids, with
      varying side chain length, were assessed for their ability to stabilize a triple
      helix. Aspartate-lysine was found to result in the most thermally stable helix
      followed by lysine-glutamate, ornithine-aspartate, and finally ornithine
      glutamate. When the sequence position of these charged amino acids was reversed
      from what is normally observed in nature, triple helix stability and
      compositional purity were significantly reduced. We examine the effect of salt on
      triple helix stability and observe that increased salt concentration reduces the
      thermal stability of heterotrimers by an average of 5  degrees C, but does not
      disrupt helix assembly. It was also found that some highly positively charged
      homotrimers can be stabilized in the presence of phosphate anions.

PMID- 22847900
TI  - Role of the rice transcription factor JAmyb in abiotic stress response.
AB  - Plants have developed certain adaptive responses to environmental stresses that
      cause adverse effects on growth. To identify genes involved in the adaptive
      mechanisms, we constructed a large population of transgenic Arabidopsis
      expressing rice full-length cDNAs, and performed gain-of-function screening under
      high-salinity stress. In this study, we identified a rice R2R3-type MYB
      transcription factor gene, JAmyb, as a gene whose overexpression causes tolerance
      to high salinity. JAmyb overexpression in transgenic Arabidopsis improved
      tolerance to high-salinity stress during seed germination, seedling growth, and
      root elongation. In rice seedlings, JAmyb expression was induced by high-salinity
      and high-osmotic stresses and reactive oxygen species (ROS), suggesting that
      JAmyb is responsible for abiotic stress response. Microarray analysis showed that
      the overexpression of JAmyb stimulates the expression of several defense
      associated genes, some of which have been predicted to be involved in osmotic
      adjustment, ROS removal, and ion homeostasis. Several transcription factors
      involved in the jasmonate (JA)-mediated stress response are also regulated by
      JAmyb. JAmyb has been reported to be associated with disease response. Our
      observations suggest that JAmyb plays a role in JA-mediated abiotic stress
      response in addition to biotic stress response in rice.

PMID- 22847902
TI  - Evaluation of image reconstruction methods for (123)I-MIBG-SPECT: a rank-order
      study.
AB  - BACKGROUND: There is an opportunity to improve the image quality and lesion
      detectability in single photon emission computed tomography (SPECT) by choosing
      an appropriate reconstruction method and optimal parameters for the
      reconstruction. PURPOSE: To optimize the use of the Flash 3D reconstruction
      algorithm in terms of equivalent iteration (EI) number (number of subsets times
      the number of iterations) and to compare with two recently developed
      reconstruction algorithms ReSPECT and orthogonal polynomial expansion on disc
      (OPED) for application on (123)I-metaiodobenzylguanidine (MIBG)-SPECT. MATERIAL
      AND METHODS: Eleven adult patients underwent SPECT 4 h and 14 patients 24 h after
      injection of approximately 200 MBq (123)I-MIBG using a Siemens Symbia T6
      SPECT/CT. Images were reconstructed from raw data using the Flash 3D algorithm at
      eight different EI numbers. The images were ranked by three experienced nuclear
      medicine physicians according to their overall impression of the image quality.
      The obtained optimal images were then compared in one further visual comparison
      with images reconstructed using the ReSPECT and OPED algorithms. RESULTS: The
      optimal EI number for Flash 3D was determined to be 32 for acquisition 4 h and 24
      h after injection. The average rank order (best first) for the different
      reconstructions for acquisition after 4 h was: Flash 3D(32) > ReSPECT > Flash
      3D(64) > OPED, and after 24 h: Flash 3D(16) > ReSPECT > Flash 3D(32) > OPED. A
      fair level of inter-observer agreement concerning optimal EI number and
      reconstruction algorithm was obtained, which may be explained by the different
      individual preferences of what is appropriate image quality. CONCLUSION: Using
      Siemens Symbia T6 SPECT/CT and specified acquisition parameters, Flash 3D(32) (4
      h) and Flash 3D(16) (24 h), followed by ReSPECT, were assessed to be the
      preferable reconstruction algorithms in visual assessment of (123)I-MIBG images.

PMID- 22847903
TI  - Detection of hepatocellular carcinoma in gadoxetic acid-enhanced MRI and
      diffusion-weighted MRI with respect to the severity of liver cirrhosis.
AB  - BACKGROUND: As gadoxetic acid-enhanced magnetic resonance imaging (MRI) and
      diffusion-weighted imaging (DWI) have been widely used for the evaluation of
      hepatocellular carcinoma (HCC), it is clinically relevant to determine the
      diagnostic efficacy of gadoxetic acid-enhanced MRI and DWI for detection of HCCs
      with respect to the severity of liver cirrhosis. PURPOSE: To compare the
      diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and DWI for
      detection of HCCs with respect to the severity of liver cirrhosis. MATERIAL AND
      METHODS: A total of 189 patients with 240 HCCs (<=3.0 cm) (Child-Pugh A, 81
      patients with 90 HCCs; Child-Pugh B, 65 patients with 85 HCCs; Child-Pugh C, 43
      patients with 65 HCCs) underwent DWI and gadoxetic acid-enhanced MRI at 3.0 T. A
      gadoxetic acid set (dynamic and hepatobiliary phase plus T2-weighted image) and
      DWI set (DWI plus unenhanced MRIs) for each Child-Pugh class were analyzed
      independently by two observers for detecting HCCs using receiver-operating
      characteristic analysis. The diagnostic accuracy and sensitivity were calculated.
      RESULTS: There was a trend toward decreased diagnostic accuracy for gadoxetic
      acid and DWI set with respect to the severity of cirrhosis (Child-Pugh A [mean
      0.974, 0.961], B [mean 0.904, 0.863], C [mean 0.779, 0.760]). For both observers,
      the sensitivities of both image sets were highest in Child-Pugh class A (mean
      95.6%, 93.9%), followed by class B (mean 83.0%, 77.1%), and class C (mean 60.6%,
      60.0%) (P < 0.05). CONCLUSION: In HCC detection, the diagnostic accuracy and
      sensitivity for gadoxetic acid-enhanced MRI and DWI were highest in Child-Pugh
      class A, followed by Child-Pugh class B, and Child-Pugh class C, indicating a
      tendency toward decreased diagnostic capability with the severity of cirrhosis.

PMID- 22847904
TI  - Multinuclear magnetic resonance studies of 2-aryl-1,3,4-thiadiazoles.
AB  - The (1) H, (13) C and (15) N spectra of aryl-substituted 1,3,4-thiadiazoles were
      recorded. The results obtained were correlated with Hammett coefficients. The
      experimental results were compared with DFT-calculated chemical shifts. The
      results obtained were compared with those for 1,3,4-oxadiazoles and 1,3,4
      selenadiazoles.

PMID- 22847905
TI  - Size-modulated synergy of cellulase clustering for enhanced cellulose hydrolysis.
AB  - Immobilization of enzymes onto nanoparticles for enhanced biocatalytic activity
      via enzyme clustering is a growing field. In this paper, the effect of
      nanoparticle size on the hydrolytic activity of artificial cellulosomes was
      investigated. A simple method based on metal affinity coordination was employed
      to directly conjugate two enzymes, an endoglucanase CelA and an exoglucanase
      CelE, onto CdSe-ZnS core-shell quantum dots (QDs) without the use of any chemical
      modification or linker molecules such as streptavidin. Artificial cellulosomes
      were created by clustering the enzymes onto two different QDs (5 and 10 nm) to
      systematically study the influence of particle size and QD to enzyme ratio on the
      enhancement in cellulose hydrolysis. Our results indicate that enzyme proximity
      is the most important factor for activity enhancement while the influence of
      particle size is relatively modest. This detailed understanding will provide
      insights for the design of other artificial cellulosomes based on nanoclustering
      of multiple catalytic domains with significantly enhanced activities, and may be
      applicable for designing improved nanobiocatalysts for biofuel production,
      bioremediation, and drug design.

PMID- 22847906
TI  - Functional magnetic resonance imaging movers and shakers: does subject-movement
      cause sampling bias?
AB  - Head movement during functional magnetic resonance imaging (fMRI) degrades data
      quality. The effects of small movements can be ameliorated during data
      postprocessing, but data associated with severe movement is frequently discarded.
      In discarding these data, it is often assumed that head-movement is a source of
      random error, and that data can be discarded from subjects with severe movement
      without biasing the sample. We tested this assumption by examining whether head
      movement was related to task difficulty and cognitive status among persons with
      multiple sclerosis (MS). Thirty-four persons with MS were scanned while
      performing a working memory task with three levels of difficulty (the N-back
      task). Maximum movement (angle, shift) was estimated for each difficulty level.
      Cognitive status was assessed by combining performance on a working memory and
      processing speed task. An interaction was found between task difficulty and
      cognitive status (high vs. low cognitive ability): there was a linear increase in
      movement as task difficulty increased that was larger among subjects with lower
      cognitive ability. Analyses of the signal-to-noise ratio (SNR) confirmed that
      increases in movement degraded data quality. Similar, though far smaller, effects
      were found in a cohort of healthy control (HC) subjects. Therefore, discarding
      data with severe movement artifact may bias MS samples such that only those with
      less-severe cognitive impairment are included in the analyses. However, even if
      such data are not discarded outright, subjects who move more (MS and HC) will
      contribute less to the group-level results because of degraded SNR.

PMID- 22847907
TI  - Same- and other-sex victimization: are the risk factors similar?
AB  - Risk factors for same- and other-sex victimization were examined in a
      longitudinal data set involving 9- to 14-year-old students. The findings
      regarding same-sex victimization supported the view that bullies select
      personally and interpersonally vulnerable targets in order to maximize their
      gains in status while minimizing loss of affection within their same-sex peer
      group. Although low self-esteem was a joint predictor of same- and other-sex
      victimization, rejection and lack of friends among other-sex peers failed to
      predict victimization by other-sex bullies, and being perceived as popular among
      other-sex peers increased the risk. Although the findings suggests that
      interpersonal risk factors for other-sex victimization differ from those found
      for same-sex victimization, they do not provide strong support for heterosexual
      interest being the basis for other-sex target selection, as suggested by some
      previous literature. As about half of the study participants were involved in the
      KiVa antibullying program, we had the possibility to examine whether the program
      effects were similar for same- and other-sex victimization. It turned out that in
      middle schools the program decreased only same-sex victimization, whereas in
      elementary school the decrease was observed regardless of the sex composition of
      bully-victim dyads.

PMID- 22847908
TI  - Peptide delivery using phospholipid micelles.
AB  - Peptide based drugs are an important class of therapeutic agents but their
      development into commercial products is often hampered due to their inherent
      physico-chemical and biological instabilities. Phospholipid micelles can be used
      to address these delivery concerns. Peptides self-associate with micelles that
      serve to thwart the aggregation of these biomolecules. Self-association with
      micelles does not modify the peptide chemically; therefore the process does not
      denature or compromise the bioactivity of peptides. Additionally, many
      amphiphilic peptides adopt alpha-helical conformation in phospholipid micelles
      which is not only the most favorable conformation for receptor interaction but
      also improves their stability against proteolytic degradation, thus making them
      long-circulating. Furthermore, the nanosize of micelles enables passive targeting
      of peptides to the desired site of action through leaky vasculature present at
      tumor and inflamed tissues. All these factors alter the pharmacokinetic and
      biodistribution profiles of peptides therefore enhance their efficacy, reduce the
      dose required to obtain a therapeutic response and prevent adverse effects due to
      interaction of the peptide with receptors present in other physiological sites of
      the body. These phospholipid micelle based peptide nanomedicines can be easily
      scaled-up and lyophilized, thus setting the stage for further development of the
      formulation for clinical use. All things considered, it can be concluded that
      phospholipid micelles are a safe, stable and effective delivery option for
      peptide drugs and they form a great promise for future peptide nanomedicines.

PMID- 22847909
TI  - In vitro antibacterial evaluation of sol-gel-derived Zn-, Ag-, and (Zn + Ag)
      doped hydroxyapatite coatings against methicillin-resistant Staphylococcus
      aureus.
AB  - Hydroxyapatite (HAp) coatings were applied using sol-gel method. Phosphor
      pentoxide and calcium nitrate were used as phosphorous and calcium precursors,
      respectively. Zinc nitrate and silver nitrate were used as substitute of calcium
      in HAp structure. As a base concentration, 1.5 wt %Ag and 2.5 wt %Zn were used.
      The weight percent of Ag was increased at 0.3 wt% and Zn content was scaled down
      at 0.5 wt%. Phase analysis and chemical bonds of synthesized materials were
      studied by XRD and FTIR. Antibacterial activity of Ag- and Zn-doped samples
      against methicilin-resistant Staphylococcus aureus (MRSA) were assessed by the
      plate-counting method. The XRD and FTIR results proved formation of HAp compound.
      Colony counting showed that silver and zinc ions prevent proliferation and growth
      of MRSA. Interestingly, co-presence of metal ions improves the antibacterial
      effectiveness of the coatings and the combined effect was greater than sum of the
      individual effects when each was administered alone. Overall, synergism between
      antibacterial activities of Zn(2+) and Ag(+) ions against MRSA can be suggested.
      Thus, cell toxicity decreases and biocompatibility increases without any
      decrement in antibacterial activity.

PMID- 22847910
TI  - Exploratory factory analysis and predicted probabilities of a Chinese version of
      Dysfunctional Voiding Symptom Score (DVSS) questionnaire.
AB  - AIMS: To evaluate the reliability, validity, and predicted probabilities of a
      Chinese version of the Dysfunctional Voiding Symptom Score (DVSS) and to explore
      the latent factors underlying dysfunctional voiding. MATERIALS AND METHODS: We
      enrolled 60 children (38 girls and 22 boys) with a diagnosis of dysfunctional
      voiding. The Chinese version of the DVSS was completed at the clinics and again 1
      week later. We enrolled 235 age- and gender-matched healthy children as the
      control group. The DVSS consisted of 10 items with each item scores 0-3. The
      internal consistency and test-retest reliability was assessed with Chronbach's
      alpha test and intraclass correlation (ICC), respectively. The predictive
      validity was analyzed using logistic regression and receiver operating
      characteristic curve analysis. Factor analysis was used to classify symptoms into
      latent factors. The bayesian method was used to adjust the predicted
      probabilities of the DVSS. RESULTS: Mean total scores of the DVSS in the cases
      and controls were 9.65 +/- 3.87 and 4.13 +/- 2.60, respectively. The alpha
      coefficient was 0.448, showing a heterogeneous composition of symptoms. Test
      retest reliability was 0.89. The chosen cut-off point for the total score of DVSS
      was 6.66, with a sensitivity of 81.67%, and specificity of 82.63%. Factor
      analysis revealed three latent variables. Using the bayesian method, the
      application of the DVSS in areas with different prevalence figures produced
      significantly different probabilities of dysfunctional voiding. CONCLUSIONS: The
      Chinese version of the DVSS is reliable with validity. With the same total score,
      we found significantly different predicted probabilities of dysfunctional
      voiding.

PMID- 22847911
TI  - Partial duplication of 13q31.3-q34 and deletion of 13q34 associated with
      diaphragmatic hernia as a sole malformation in a fetus.
AB  - Partial duplications and deletions of chromosome 13 are rare and the phenotypic
      expressions of both aneuploidies are highly variable. Here we report on a fetus
      diagnosed prenatally with partial trisomy of 13q and a diaphragmatic hernia as a
      sole malformation. The parents had decided to terminate the pregnancy after the
      finding of diaphragmatic hernia by ultrasound scan, which was also confirmed by
      autopsy of the fetus. Subsequently chromosome analysis, fluorescence in situ
      hybridization (FISH), and array comparative genomic hybridization (array CGH) was
      carried out on fetal tissue. The chromosome analysis revealed additional material
      on chromosome 13, which was shown to be from the same chromosome, by FISH
      analysis. Array CGH demonstrated a partial duplication and a small deletion at
      the distal long arm of chromosome 13. The parents had normal karyotypes. This is
      the first case of a de novo pure partial duplication of 13q31.3-q34 and distal
      deletion of 13q34 with a phenotype apparently only involving a diaphragmatic
      hernia and three lung lobes on both sides. Microarray analysis was useful in
      refining the chromosomal imbalance and suggesting a candidate region for
      diaphragmatic hernia.

PMID- 22847912
TI  - Innovation paper in the June 2012 edition of the Journal of Digital Imaging
      (JDI).

PMID- 22847914
TI  - Enantioselective hydrogenation of alpha-substituted acrylic acids catalyzed by
      iridium complexes with chiral spiro aminophosphine ligands.

PMID- 22847913
TI  - Image quality in real-time teleultrasound of infant hip exam over low-bandwidth
      internet links: a transatlantic feasibility study.
AB  - Evolution of communication systems, especially internet-based technologies, has
      probably affected Radiology more than any other medical specialty. Tremendous
      increase in internet bandwidth has enabled a true revolution in image
      transmission and easy remote viewing of the static images and real-time video
      stream. Previous reports of real-time telesonography, such as the ones developed
      for emergency situations and humanitarian work, rely on high compressions of
      images utilized by remote sonologist to guide and supervise the unexperienced
      examiner. We believe that remote sonology could be also utilized in
      teleultrasound exam of infant hip. We tested feasibility of a low-cost
      teleultrasound system for infant hip and performed data analysis on the
      transmitted and original images. Transmission of data was accomplished with
      Remote Ultrasound (RU), a software package specifically designed for
      teleultrasound transmission through limited internet bandwidth. While image
      analysis of image pairs revealed statistically significant loss of information,
      panel evaluation failed to recognize any clinical difference between the original
      saved and transmitted still images.

PMID- 22847915
TI  - Two-dimensional oxides: multifunctional materials for advanced technologies.
AB  - The last decade has seen spectacular progress in the design, preparation, and
      characterization down to the atomic scale of oxide ultrathin films of few
      nanometers thickness grown on a different material. This has paved the way
      towards several sophisticated applications in advanced technologies. By playing
      around with the low-dimensionality of the oxide layer, which sometimes leads to
      truly two-dimensional systems, one can exploit new properties and functionalities
      that are not present in the corresponding bulk materials or thick films. In this
      review we provide some clues about the most recent advances in the design of
      these systems based on modern electronic structure theory and on their
      preparation and characterization with specifically developed growth techniques
      and analytical methods. We show how two-dimensional oxides can be used in mature
      technologies by providing added value to existing materials, or in new
      technologies based on completely new paradigms. The fields in which two
      dimensional oxides are used are classified based on the properties that are
      exploited, chemical or physical. With respect to chemical properties we discuss
      use of oxide ultrathin films in catalysis, solid oxide fuel cells, gas sensors,
      corrosion protection, and biocompatible materials; regarding the physical
      properties we discuss metal-oxide field effect transistors and memristors,
      spintronic devices, ferroelectrics and thermoelectrics, and solar energy
      materials.

PMID- 22847916
TI  - Roles of cytokines and progesterone in the regulation of the nitric oxide
      generating system in bovine luteal endothelial cells.
AB  - Nitric oxide (NO) produced by luteal endothelial cells (LECs) plays important
      roles in regulating corpus luteum (CL) function, yet the local mechanism
      regulating NO generation in bovine CL remains unclear. The purpose of the present
      study was to elucidate if tumor necrosis factor-alpha (TNF), interferon gamma
      (IFNG), and/or progesterone (P4) play roles in regulating NO generating system in
      LECs. Cultured bovine LECs obtained from the CL at the mid-luteal stage (Days 8
      12 of the cycle) were treated for 24 hr with TNF (2.9 nM), IFNG (2.5 nM), or P4
      (0.032-32 uM). NO production was increased by TNF and IFNG, but decreased by P4
      (P < 0.05). TNF and IFNG stimulated the relative steady-state amounts of
      inducible nitric oxide synthase (iNOS) mRNA and iNOS protein expression (P <
      0.05), whereas P4 inhibited relative steady-state amounts of iNOS mRNA and iNOS
      protein expression (P < 0.05). In contrast, endothelial nitric oxide synthase
      (eNOS) expression was not affected by any treatment. TNF and IFNG stimulated NOS
      activity (P < 0.05) and 1400W, a specific inhibitor of iNOS, reduced NO
      production stimulated by TNF and IFNG in LECs (P < 0.05). Onapristone, a specific
      P4 receptor antagonist, blocked the inhibitory effect of P4 on NO production in
      LECs (P < 0.05). The overall findings suggest that TNF and IFNG accelerate
      luteolysis by increasing NO production via stimulation of iNOS expression and NOS
      activity in bovine LECs. P4, on the other hand, may act in maintaining CL
      function by suppressing iNOS expression in bovine LECs.

PMID- 22847917
TI  - Renal dysfunction in liver transplant recipients: evaluation of the critical
      issues.
AB  - Major progress has been made in the field of liver transplantation since the
      first procedure was performed nearly 50 years ago. Despite these improvements,
      renal dysfunction before and after liver transplantation remains a major
      complicating factor associated with increased health care costs, morbidity, and
      mortality. Creatinine-based estimates of renal function are inaccurate in the
      setting of end-stage liver disease and often lead to underdiagnosis and late
      intervention. This issue is critical in that it is important to understand both
      the etiology and chronicity of renal dysfunction before liver transplantation
      because the treatment clearly varies, especially with respect to simultaneous
      liver-kidney (SLK) transplantation. Because of the scarcity of available grafts,
      identifying appropriate candidates for SLK transplantation is crucial.
      Hepatorenal syndrome is common in liver transplant candidates; however, other
      etiologies of renal dysfunction need to be considered. Renal dysfunction after
      liver transplantation is common and may have an acute or chronic presentation.
      Although calcineurin inhibitors (CNIs) have been associated with post-liver
      transplant nephrotoxicity, their role may be overestimated, and other
      contributing etiologies should remain in a clinician's differential diagnosis.
      Alternatives to CNIs have been evaluated; however, a safe immunosuppressive
      regimen that achieves the preservation of renal function in liver transplant
      recipients remains to be established. In this review of the literature, renal
      dysfunction in the setting of liver transplantation is evaluated, and the
      critical issues that are barriers to improved outcomes are highlighted.

PMID- 22847918
TI  - Exploring the combinatorial genomic space in Escherichia coli for ethanol
      tolerance.
AB  - Strain tolerance to toxic chemicals is desirable for biologically producing
      biofuels and chemicals. Standard genomic libraries can be screened to identify
      genes imparting tolerance, but cannot capture interactions among proximal or
      distant loci. In search of ethanol tolerance determinants, we expanded the
      genomic space combinatorially by screening coexisting genomic libraries (CoGeLs)
      of fosmids (large inserts) and plasmids (smaller inserts) under increasing
      ethanol concentrations. Such screening led to identification of interacting
      genetic loci imparting ethanol tolerance. One pair of fragments ([galT, galE] and
      [recA, pncC, mltB]) increased survival under 50 g/L ethanol by 38% when
      coexpressed, but individually the fragments had no effect. Coexpression of two
      genomic fragments ([sfsB, murA, yrbA, mlaB, mlaC, mlaD, mlaE, mlaF, yrbG] and
      [yrbA, mlaB, mlaC]) enhanced Escherichia coli survival to 50 g/L ethanol by up to
      115%. A 35-kb fosmid fragment increased tolerance to 63 g/L ethanol by 160%.
      While the tolerance levels of these strains compare favorably to or exceed the
      performance of previously reported engineered strains, more significantly, this
      study demonstrates that combinatorial library screening and screening fosmid
      libraries offer new, previously unexplored tools for identifying genetic
      determinants of ethanol, and by extrapolation, other alcohol tolerance.

PMID- 22847919
TI  - Detection of altered hippocampal morphology in multiple sclerosis-associated
      depression using automated surface mesh modeling.
AB  - Depression is very common in multiple sclerosis (MS) but the underlying
      biological mechanisms are poorly understood. The hippocampus plays a key role in
      mood regulation and is implicated in the pathogenesis of depression. This study
      utilizes volumetric and shape analyses of the hippocampus to characterize
      neuroanatomical correlates of depression in MS. A cross-section of 109 female
      patients with MS was evaluated. Bilateral hippocampi were segmented from MRI
      scans (volumetric T1 -weighted, 1 mm(3) ) using automated tools. Shape analysis
      was performed using surface mesh modeling. Depression was assessed using the
      Center for Epidemiologic Studies-Depression (CES-D) scale. Eighty-three subjects
      were classified as low depression (CES-D 0-20) versus 26 subjects with high
      depression (CES-D >= 21). Right hippocampal volumes (P = 0.04) were smaller in
      the high depression versus the low depression groups, but there was no
      significant difference in left hippocampal volumes. Surface rendering analysis
      revealed that hippocampal shape changes in depressed patients with MS were
      clustered in the right hippocampus. Significant associations were found between
      right hippocampal shape and affective symptoms but not vegetative symptoms of
      depression. Our results suggested that regionally clustered reductions in
      hippocampal thickness can be detected by automated surface mesh modeling and may
      be a biological substrate of MS depression in female patients.

PMID- 22847920
TI  - Electrical stimuli to increase cell proliferation on carbon nanotubes/mesoporous
      silica composites for drug delivery.
AB  - The development of smart materials as bone implants is nowadays a challenging
      task to optimize their fast osteointegration. Nevertheless, no attempts have been
      done in joining the possibility of using electrical stimulation and drug delivery
      together in a material intended for bone tissue engineering. Moreover, the use of
      this synergy to induce bone healing is still limited until novel drug reservoirs
      material formulations allow an efficient applicability of the electrical stimuli.
      Herein, we present the biological response of osteoblasts cells, cultured over
      carbon nanotubes-mesoporous silica composites while exposed to external
      electrical stimulus. Moreover, its ability to function as drug delivery systems
      is also demonstrated. Bone cell metabolism was stimulated and mitochondrial
      activity was increased up to seven times in the presence of these composites
      under electrical stimulus, suggesting their potential application in bone
      regeneration processes.

PMID- 22847921
TI  - Iridium-catalyzed oxidant-free dehydrogenative C-H bond functionalization:
      selective preparation of N-arylpiperidines through tandem hydrogen transfers.

PMID- 22847923
TI  - A luminescent and sublimable Dy(III)-based single-molecule magnet.
AB  - The reaction of [Ln(hfac)(3)].2H(2)O and pyridine-N-oxide (PyNO) leads to
      isostructural dimers of the formula [Ln(hfac)(3)(PyNO)](2) (Ln=Eu, Gd, Tb, Dy).
      The Dy derivative shows a remarkable single-molecule magnet behavior with complex
      hysteresis at 1.4 K. The dynamics of the magnetization features are two
      relaxation regimes: a thermally activated one at high temperature (tau(0)=(5.62+/
      0.4)*10(-11) s and Delta=(167+/-1) K) and a quantum tunneling regime at low
      temperature with a tunneling frequency of 0.42 Hz. The analysis of the Gd
      derivative evidences intradimer antiferromagnetic interactions (J=(-0.034+/
      0.001) cm(-1)). Moreover, the Eu, Tb, and Dy derivatives are luminescent with
      quantum yield of 51, 53, and 0.1%, respectively. The thermal investigation of
      [Dy(hfac)(3)(PyNO)](2) shows that the dimers can be sublimated intact, suggesting
      their possible exploit as active materials for surface-confined nanostructures to
      be investigated by fluorimetry methods.

PMID- 22847924
TI  - Robust preparative-scale extracellular production of hirudin in Escherichia coli
      and its purification and characterization.
AB  - Hirudin variant III (HV3) is potentially useful in the prevention and treatment
      of cataracts. To prepare sufficient amounts of rHV3 for further preclinical
      studies, we developed an effective process for robust preparative-scale
      extracellular production of rHV3 in Escherichia coli. In a 7-l bioreactor, under
      the optimal fed-batch fermentation conditions, rHV3 was excreted into the culture
      supernatant and yielded up to 915 mg l(-1). Then, a four-step purification
      procedure was applied to the product, which included ultrafiltration, hydrophobic
      chromatography, anion-exchange chromatography, and preparative reversed-phase
      fast protein liquid chromatography (FPLC). The overall maximum recovery attained
      was 56 %, the purity reached at least 99 % as evaluated by HPLC analysis, the
      molecular weight was determined to be 7,011.10 Da by matrix-assisted laser
      desorption time-of-flight mass spectrometry (MALDI-TOF/MS) analysis, and the pI
      was 4.46 as analyzed by isoelectric focusing. The N- and C-terminal sequence
      analysis confirmed the product homogeneity. The final product contained at most
      10 pg of residual DNA per dose (0.2 mg) of rHV3 by high-sensitivity hybridization
      assay and at most 3 EU endotoxin protein/mg by limulus amebocyte lysate assay.
      Taken together, the rHV3 produced in multigram quantities in E. coli by this
      bioprocess meets the regulatory criteria for biopharmaceuticals and can be used
      as a drug candidate for preclinical studies.

PMID- 22847925
TI  - Gynecologic and obstetric implications of the joint hypermobility syndrome
      (a.k.a. Ehlers-Danlos syndrome hypermobility type) in 82 Italian patients.
AB  - Joint hypermobility syndrome (JHS) emerges as likely the most common clinical
      form of Ehlers-Danlos syndrome. Given the striking predominance of affected
      women, practitioners often face gynecologic and obstetric issues. However, their
      decisions are still based on personal experience rather than literature due to
      the lack of a consistent body of evidence. We collected a set of gynecologic and
      obstetric features in 82 post-puberal women with JHS attending two Italian
      centers. Common gynecologic findings were dysmenorrhea (82.9%),
      meno/metrorrhagias (53.7%), irregular menses (46.3%), and dispareunia/vulvodinia
      (31.7%). Forty women were nulliparous and 42 had one or more pregnancy for a
      total of 93 diagnosed conceptions. Of them, 16.1% were spontaneous abortions,
      6.5% voluntary interruptions, 10.7% preterm deliveries, and 66.7% deliveries at
      term. Overall outcome of proceeding pregnancies was good with no stillbirth and
      fetal/neonatal hypoxic/ischemic event. Non-operative vaginal delivery was
      registered in 72.2%, forceps/vacuum use in 5.5% and cesarean in 22.3%.
      Local/total anesthesia was successfully performed in 17 pregnancies without any
      problem. Major post-partum complications included abnormal scar formation after
      cesarean or episiotomy (46.1%), hemorrhage (19.4%), pelvic prolapses (15.3%),
      deep venous thrombosis (4.2%), and coccyx dislocation (1.4%). Prolapses were the
      most clinically relevant complication and associated with episiotomy. Gathered
      data were discussed for practically oriented considerations.

PMID- 22847922
TI  - Regulation of the ovarian reserve by members of the transforming growth factor
      beta family.
AB  - Genetic or environmental factors that affect the endowment of oocytes, their
      assembly into primordial follicles, or their subsequent entry into the growing
      follicle pool can disrupt reproductive function and may underlie disorders such
      as primary ovarian insufficiency. Mouse models have been instrumental in
      identifying genes important in ovarian development, and a number of genes now
      associated with ovarian dysfunction in women were first identified as causing
      reproductive defects in knockout mice. The transforming growth factor beta (TGFB)
      family consists of developmentally important growth factors that include the
      TGFBs, anti-Mullerian hormone (AMH), activins, bone morphogenetic proteins
      (BMPs), and growth and differentiation factor 9 (GDF9). The ovarian primordial
      follicle pool is the source of oocytes in adults. Development of this pool can be
      grossly divided into three key processes: (1) establishment of oocytes during
      embryogenesis followed by (2) assembly and (3) activation of the primordial
      follicle. Disruptions in any of these processes may cause reproductive
      dysfunction. Most members of the TGFB family show pivotal roles in each of these
      areas. Understanding the phenotypes of various mouse models for this protein
      family will be directly relevant to understanding how disruptions in TGFB family
      signaling result in reproductive diseases in women and will present new areas for
      development of tailored diagnostics and interventions for infertility.

PMID- 22847926
TI  - Application of the buccal micronucleus cytome assay and analysis of PON1Gln192Arg
      and CYP2A6*9(-48T>G) polymorphisms in tobacco farmers.
AB  - Tobacco is a major Brazilian cash crop. Tobacco farmers apply large amounts of
      pesticides to control insect growth. Workers come into contact with green tobacco
      leaves during the tobacco harvest and absorb nicotine through the skin. In the
      present study, micronucleus frequency, cell death, and the frequency of basal
      cells were measured in tobacco farmers using the buccal micronucleus cytome assay
      (BMCyt), in parallel with measurement of blood butyrylcholinesterase (BChE) and
      nicotine levels. Polymorphisms in PONIGln192Arg and CYP2A6*9(-48T>G) were
      evaluated to verify the relationship between genetic susceptibility and the
      measured biomarkers. Peripheral blood and buccal cell samples were collected from
      106 agricultural workers, at two different crop times (during pesticide
      application and leaf harvest), as well as 53 unexposed controls. BMCyt showed
      statistically significant increases in micronuclei, nuclear buds, and binucleated
      cells among exposed subjects in differentiated cells, and in micronuclei in basal
      cells. In addition, the exposed group showed higher values for condensed
      chromatin, karyorrhectic, pyknotic, and karyolitic cells, indicative of cell
      death, and an increase in the frequency of basal cells compared to the unexposed
      control group. A slight difference in mutagenicity using the BMCyt assay was
      found between the two different sampling times (pesticide application and leaf
      harvest), with higher micronucleus frequencies during pesticide application.
      Elevated cotinine levels were observed during the leaf harvest compared to the
      unexposed controls, while BChE level was similar among the farmers and controls.
      PONIGln192Arg and CYP2A6*9(-48T>G) polymorphisms were associated with DNA damage
      induced by pesticides and cell death.

PMID- 22847927
TI  - Physiological behavior of quantum dots.
AB  - Quantum dots (QDs) have shown great potentials in biomedical applications like
      bioimaging, sensors and diagnostics due to various advantages such as their
      robust fluorescence, remarkable photostability, large absorption cross section,
      and tunable fluorescence emission. The fate, behavior, metabolism, and toxicities
      of QDs are the primary aspects to be assessed before their bio-applications.
      Numerous studies concerning those aspects have been reported in the past years.
      However, only several reviews discussed the toxicities of QDs and various
      contradictory conclusions appear between these studies. In this review, the fate,
      metabolism, and behaviors of various QDs and crucial parameters that may
      determine their fate and behavior in vivo are discussed in depth. This review may
      provide insights for a better understanding of the biological impacts of QDs. We
      also propose several suggestions for how to develop QDs application in humans in
      the future.

PMID- 22847928
TI  - Anatomy of the foot venous pump: physiology and influence on chronic venous
      disease.
AB  - The aim of this paper is to demonstrate the location of the venous foot pump
      using an anatomical study. Four hundred cadaveric feet were injected with green
      neoprene latex followed by a dissection. A coloured segmentation of the venous
      system was achieved. The Lejars' concept of the venous sole of the foot is
      incorrect: the true blood venous reservoir of the foot is located deeply in the
      plantar veins, between the plantar muscles. The medial and mostly lateral plantar
      veins converge into the plexus shaped calcaneal crossroad, where the blood is
      ejected upwards into the two posterior tibial veins. In addition, the several
      medial perforators of the foot directly connect the deep system (medial plantar
      veins) to the superficial venous system (medial marginal vein). This forms a true
      'medial functional unit' which is unique in the limb given its directional flow
      is from deep to superficial. In conclusion, the plantar veins play an important
      role in the physiology of the venous return since a venous reservoir of 25 mL of
      blood is mobilized upwards with each step during walking. Therefore, the
      impairment of the foot pump by a static foot disorder should be considered as an
      important risk factor for chronic venous disease, and should be evaluated and
      corrected in any patient with venous insufficiency.

PMID- 22847930
TI  - Excitatory and inhibitory mechanisms underlying somatosensory habituation.
AB  - Habituation is a basic process of learning in which repeated exposure to a
      sensory stimulus leads to a decrease in the strength of neuronal activations and
      behavioral responses. In addition to increases in neuronal activity, sensory
      stimuli can also lead to decreases in neuronal activity. Until now, the effects
      of habituation on stimulus-induced neuronal deactivations have not been
      investigated. We performed functional magnetic resonance imaging in 30 healthy
      subjects during repetitive unilateral somatosensory stimulation and combined this
      analysis with a psychophysiological examination of changes in the perception
      threshold. Consistent with the literature, we found a time-dependent decrease of
      the positive blood oxygenation level-dependent (BOLD) response (indicative of
      habituation) in the primary somatosensory cortex (SI) contralateral to the
      stimulus. In contrast, the negative BOLD response (NBR) in the ipsilateral SI did
      not show a decrease in amplitude; instead, an increase in amplitude was found,
      i.e., a stronger NBR (increased response). The increased NBR was associated with
      an increased perception threshold of the nonstimulated hand. These findings
      suggest that habituation is not primarily characterized by a decrease in the
      neuronal response to repeated stimuli but rather a widespread change in the
      balance between excitatory and inhibitory effects that favors inhibitory effects.

PMID- 22847929
TI  - Comparison of mutation findings in ZIC2 between microform and classical
      holoprosencephaly in a Brazilian cohort.
AB  - BACKGROUND: Holoprosencephaly is the most frequent congenital malformation of the
      forebrain in humans. It is anatomically classified by the relative degree of
      abnormal formation and separation of the developing central nervous system.
      Mutations of ZIC2 are the second most common heterozygous variations detected in
      holoprosencephaly (HPE) patients. Mutations in most known HPE genes typically
      result in variable phenotypes that rage from classic alobar HPE to microforms
      represented by hypotelorism, solitary central maxillary incisor (SCMI), and cleft
      lip/palate, among others. Patients with HPE owing to ZIC2 mutations have recently
      been described by a distinct phenotype compared with mutations in other HPE
      causative genes. METHODS: We report the comparison of ZIC2 molecular findings by
      Sanger bidirectional DNA sequencing and ad hoc genotyping in a cohort of 105
      Brazilian patients within the clinical spectrum of HPE, including classic and
      microform groups. RESULTS: We detected a total of five variants in the ZIC2 gene:
      a common histidine tract expansion c.716_718dup (p.His239dup), a rare
      c.1377_1391del_homozygous (p.Ala466_470del, or Ala 15 to 10 contraction), a novel
      intronic c.1239+18G>A variant, a novel frameshift c.1215dupC (p.Ser406Glnfs*11),
      and a c.1401_1406dup (p.Ala469_470dup, or alanine tract expansion to 17
      residues). CONCLUSIONS: From these patients, only the latter two mutations found
      in classic HPE are likely to be medically significant. In contrast, variants
      detected in the microform group are not likely to be pathogenic. We show
      conclusively that the histidine tract expansion is a polymorphic alteration that
      demonstrates considerable differences in allele frequencies across different
      ethnic groups. Therefore, careful population studies of rare variants can improve
      genotype-phenotype correlations. Birth Defects Research (Part A) 2012.

PMID- 22847931
TI  - Deep architectures for protein contact map prediction.
AB  - MOTIVATION: Residue-residue contact prediction is important for protein structure
      prediction and other applications. However, the accuracy of current contact
      predictors often barely exceeds 20% on long-range contacts, falling short of the
      level required for ab initio structure prediction. RESULTS: Here, we develop a
      novel machine learning approach for contact map prediction using three steps of
      increasing resolution. First, we use 2D recursive neural networks to predict
      coarse contacts and orientations between secondary structure elements. Second, we
      use an energy-based method to align secondary structure elements and predict
      contact probabilities between residues in contacting alpha-helices or strands.
      Third, we use a deep neural network architecture to organize and progressively
      refine the prediction of contacts, integrating information over both space and
      time. We train the architecture on a large set of non-redundant proteins and test
      it on a large set of non-homologous domains, as well as on the set of protein
      domains used for contact prediction in the two most recent CASP8 and CASP9
      experiments. For long-range contacts, the accuracy of the new CMAPpro predictor
      is close to 30%, a significant increase over existing approaches. AVAILABILITY:
      CMAPpro is available as part of the SCRATCH suite at
      http://scratch.proteomics.ics.uci.edu/. CONTACT: pfbaldi@uci.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22847932
TI  - easyRNASeq: a bioconductor package for processing RNA-Seq data.
AB  - MOTIVATION: RNA sequencing is becoming a standard for expression profiling
      experiments and many tools have been developed in the past few years to analyze
      RNA-Seq data. Numerous 'Bioconductor' packages are available for next-generation
      sequencing data loading in R, e.g. ShortRead and Rsamtools as well as to perform
      differential gene expression analyses, e.g. DESeq and edgeR. However, the
      processing tasks lying in between these require the precise interplay of many
      Bioconductor packages, e.g. Biostrings, IRanges or external solutions are to be
      sought. RESULTS: We developed 'easyRNASeq', an R package that simplifies the
      processing of RNA sequencing data, hiding the complex interplay of the required
      packages behind a single functionality. AVAILABILITY: The package is implemented
      in R (as of version 2.15) and is available from Bioconductor (as of version 2.10)
      at the URL: http://bioconductor.org/packages/release/bioc/html/easyRNASeq.html,
      where installation and usage instructions can be found. CONTACT:
      delhomme@embl.de.

PMID- 22847934
TI  - A MATLAB toolbox for structural kinetic modeling.
AB  - SUMMARY: Structural kinetic modeling (SKM) enables the analysis of dynamical
      properties of metabolic networks solely based on topological information and
      experimental data. Current SKM-based experiments are hampered by the time
      intensive process of assigning model parameters and choosing appropriate sampling
      intervals for Monte-Carlo experiments. We introduce a toolbox for the automatic
      and efficient construction and evaluation of structural kinetic models (SK
      models). Quantitative and qualitative analyses of network stability properties
      are performed in an automated manner. We illustrate the model building and
      analysis process in detailed example scripts that provide toolbox implementations
      of previously published literature models. AVAILABILITY: The source code is
      freely available for download at http://bioinformatics.uni
      potsdam.de/projects/skm. CONTACT: girbig@mpimp-golm.mpg.de.

PMID- 22847933
TI  - An integrated approach to reduce the impact of minor allele frequency and linkage
      disequilibrium on variable importance measures for genome-wide data.
AB  - MOTIVATION: There is growing momentum to develop statistical learning (SL)
      methods as an alternative to conventional genome-wide association studies (GWAS).
      Methods such as random forests (RF) and gradient boosting machine (GBM) result in
      variable importance measures that indicate how well each single-nucleotide
      polymorphism (SNP) predicts the phenotype. For RF, it has been shown that
      variable importance measures are systematically affected by minor allele
      frequency (MAF) and linkage disequilibrium (LD). To establish RF and GBM as
      viable alternatives for analyzing genome-wide data, it is necessary to address
      this potential bias and show that SL methods do not significantly under-perform
      conventional GWAS methods. RESULTS: Both LD and MAF have a significant impact on
      the variable importance measures commonly used in RF and GBM. Dividing SNPs into
      overlapping subsets with approximate linkage equilibrium and applying SL methods
      to each subset successfully reduces the impact of LD. A welcome side effect of
      this approach is a dramatic reduction in parallel computing time, increasing the
      feasibility of applying SL methods to large datasets. The created subsets also
      facilitate a potential correction for the effect of MAF using pseudocovariates.
      Simulations using simulated SNPs embedded in empirical data-assessing varying
      effect sizes, minor allele frequencies and LD patterns-suggest that the
      sensitivity to detect effects is often improved by subsetting and does not
      significantly under-perform the Armitage trend test, even under ideal conditions
      for the trend test. AVAILABILITY: Code for the LD subsetting algorithm and
      pseudocovariate correction is available at http://www.nd.edu/~glubke/code.html.

PMID- 22847935
TI  - GlycoCD: a repository for carbohydrate-related CD antigens.
AB  - SUMMARY: The open access comprehensive GlycoCD database application is for
      representation and retrieval of carbohydrate-related clusters of differentiation
      (CDs). The main objective of this database platform is to provide information
      about interactions of carbohydrate moieties with proteins that are important for
      identification of specific cell surface molecule with a focus on the integration
      of data from carbohydrate microarray databases. GlycoCD database comprises two
      sections: the carbohydrate recognition CD and glycan CD. It allows easy access
      through a user-friendly web interface to all carbohydrate-defined CDs and those
      that interact with carbohydrates along with other relevant information.
      AVAILABILITY: The database is freely available at
      http://glycosciences.de/glycocd/index.php CONTACT: r.s-albiez@dkfz.de.

PMID- 22847936
TI  - EuGene: maximizing synthetic gene design for heterologous expression.
AB  - Numerous software applications exist to deal with synthetic gene design, granting
      the field of heterologous expression a significant support. However, their
      dispersion requires the access to different tools and online services in order to
      complete one single project. Analyzing codon usage, calculating codon adaptation
      index (CAI), aligning orthologs and optimizing genes are just a few examples. A
      software application, EuGene, was developed for the optimization of multiple gene
      synthetic design algorithms. In a seamless automatic form, EuGene calculates or
      retrieves genome data on codon usage (relative synonymous codon usage and CAI),
      codon context (CPS and codon pair bias), GC content, hidden stop codons,
      repetitions, deleterious sites, protein primary, secondary and tertiary
      structures, gene orthologs, species housekeeping genes, performs alignments and
      identifies genes and genomes. The main function of EuGene is analyzing and
      redesigning gene sequences using multi-objective optimization techniques that
      maximize the coding features of the resulting sequence. AVAILABILITY: EuGene is
      freely available for non-commercial use, at http://bioinformatics.ua.pt/eugene.

PMID- 22847937
TI  - Enantioselective addition of cyclic enol silyl ethers to 2-alkenoyl-pyridine-N
      oxides catalysed by Cu(II)-bis(oxazoline) complexes.
AB  - Asymmetric reactions involving (E)-3-aryl-1-(pyridin-2-yl-N-oxide)prop-2-en-1
      ones and cyclic enol silyl ethers show good yields and excellent
      enantioselectivities (up to 99.9 % ee) when catalysed by bis(oxazoline)-Cu(II) 
      complexes. Different reaction pathways can be followed by different enol silyl
      ethers: with 2-(trimethylsilyloxy)furan, a Mukaiyama-Michael adduct is obtained,
      whereas a hetero Diels-Alder cycloadduct was formed by using (1,2
      dihydronaphthalen-4-yloxy)trimethylsilane. In the latter reaction, the absolute
      configuration of the product is consistent with a reagent approach to the less
      hindered Re face of the coordinated substrate in the reactive complex.

PMID- 22847940
TI  - Self-assembly of vertically aligned gold nanorod arrays on patterned substrates.

PMID- 22847941
TI  - Study on in vitro release and cell response to alendronate sodium-loaded
      ultrahigh molecular weight polyethylene loaded with alendronate sodium wear
      particles to treat the particles-induced osteolysis.
AB  - The aim of this study is to investigate in vitro release and cell response to
      wear particles of ultrahigh molecular weight polyethylene loaded with alendronate
      sodium (UHMWPE-ALN), a potent bone resorption inhibitor. Wear particles of UHMWPE
      ALN with different ALN contents (0.5 wt % or 1.0 wt %) and size ranges (<45 MUm
      or 45-75 MUm) were cocultured with macrophages (RAW264.7) and osteoblasts (MC3T3
      E1), respectively. The in vitro ALN release was divided into three stages: an
      initial burst release, subsequent rapid release, and final slow release. The
      particle size and ALN content of UHMWPE-ALN wear particles affected the in vitro
      release mainly during initial burst and rapid release. Compared with the control
      cells, UHMWPE-ALN wear particles stimulated a significant elevation of tumor
      necrosis factor-alpha (TNF-alpha) release from macrophages but had no obvious
      effect on interleukin-6 release. However, this stimulation of TNF-alpha release
      could be reduced by ALN released from UHMWPE-ALN wear particles. The wear
      particle size had stronger effect of on the macrophages compared with the ALN
      concentration. After coculture with UHMWPE-ALN wear particles, osteoblast
      proliferation and alkaline phosphatase activities increased moderately with the
      increase in particle sizes and ALN concentrations. These results suggest that
      incorporation of ALN in UHMWPE-ALN may be an effective approach to prevent or
      reduce particles-induced osteolysis.

PMID- 22847942
TI  - Bixin and norbixin protect against DNA-damage and alterations of redox status
      induced by methylmercury exposure in vivo.
AB  - Populations in the Amazon are exposed to organic mercury via consumption of
      contaminated foods. These ethnic groups consume a specific plant seed "annatto"
      which contains certain carotenoids. The aim of this study was to find out if
      these compounds (bixin, BIX and norbixin, NOR), protect against DNA-damage caused
      by the metal. Therefore, rats were treated orally with methylmercury (MeHg) and
      with the carotenoids under conditions that are relevant to humans. The animals
      were treated either with MeHg (30 MUg/kg/bw/day), BIX (0.1-10 mg/kg/bw/day), NOR
      (0.01-1.0 mg/kg/bw/day) or combinations of the metal compound and the carotenoids
      consecutively for 45 days. Subsequently, the glutathione levels (GSH) and the
      activity of catalase were determined, and DNA-damage was measured in hepatocytes
      and leukocytes using single cell gel electrophoresis assays. Treatment with the
      metal alone caused a decrease in the GSH levels (35%) and induced DNA damage,
      which resulted in increased DNA migration after electrophoresis in liver and
      blood cells, whereas no effects were seen with the carotenoids alone. When BIX or
      NOR were given in combination with organic mercury, the intermediate and the
      highest concentrations of the carotenoids (1.0 and 10.0 mg/kg/bw/day BIX and 0.1
      and 1.0 mg/kg/bw/day NOR) protected against DNA-damage. Furthermore, we found
      with both carotenoids, a moderate increase in the GSH levels in both metal
      treated and untreated animals, while the activities of catalase remained
      unchanged. Our results indicate that consumption of BIX and NOR may protect
      humans against the adverse health effects caused by exposure to organic mercury.

PMID- 22847943
TI  - RNA polymerase II transcriptional silencing in growing and fully grown germinal
      vesicle oocytes isolated from gonadotropin-stimulated and non-stimulated gilts.
AB  - Global transcription silencing occurs in the oocyte during its final phase of
      growth. The particular mechanism of this silencing is not well understood. Here,
      we investigated the silencing of RNA polymerase II transcription in porcine
      oocytes. First, we investigated the transcriptional activity of germinal vesicle
      oocytes derived from stimulated and non-stimulated gilts, but no transcriptional
      activity was observed. Second, we focused on the fate of RNA polymerase II in
      growing and fully grown oocytes. Active and inactive forms of RNA polymerase II
      were detected in growing oocytes by immunofluorescence and Western blots. In
      contrast, only the inactive form of RNA polymerase II was detected in fully grown
      oocytes. To evaluate if the inactive form of RNA polymerase II is released from
      DNA, the oocytes were subsequently permeabilized and fixed in one step. After
      this modified fixation protocol, the immunofluorescent labeling was negative in
      fully grown oocytes, but remained unchanged (positive) in growing oocytes. These
      results indicate that the inactive form of RNA polymerase II is not bound to DNA
      during the oocyte growth. Finally, based on Western blot analysis of different
      stages of oocyte maturation, the inactive form of RNA polymerase II was detected
      in metaphase I but not in metaphase II. Our study confirmed the global
      transcription silencing of fully grown oocytes. Compared with other mammalian
      species (e.g., mouse), the mechanism of RNA polymerase II silencing in porcine
      oocytes seems to be similar, despite some differences in dynamics.

PMID- 22847945
TI  - Growth curves of Egyptian patients with Turner syndrome.
AB  - This study analyzes the body anthropometric measurements in females with Turner
      syndrome (TS) not treated with recombinant human growth hormone. Height, weight,
      head circumference, and body mass index (BMI) data were collected from 93
      patients. Their ages ranged from 6 months to 24 years (mean 10 +/- 4.3 years).
      Chromosomal analysis revealed: 55 patients with 45,X and 38 patients with mosaic
      karyotypes. Patients were divided into yearly age groups. Standard growth curves
      were constructed for these Egyptian Turner syndrome (TS) patients. Mean and
      standard deviations were estimated across the age groups. When comparing the mean
      heights of patients to the Egyptian standards, short stature (<=2 SD) was found
      in 96.8% of patients older than 6 years. Patients' mean weight and BMI were
      higher than controls. The mean height of the studied Egyptian patients was
      slightly lower than that of females with TS in UK and European patients.
      Therefore, local reference values are more appropriate than International
      standards. The charts presented here can be used to optimize routine healthcare
      for Egyptian TS patients. The use of growth charts specific for Egyptian TS
      patients can help to discover early physical developmental delay and suggests the
      necessity of looking for concomitant diseases affecting growth.

PMID- 22847944
TI  - Association between weight gain during pregnancy and neural tube defects and
      gastroschisis in offspring.
AB  - BACKGROUND: Limited information is available about the association of maternal
      weight gain during pregnancy and birth defects. The objective of this study was
      to investigate the association of maternal weight gain with neural tube defects
      (NTDs) and gastroschisis among offspring. METHODS: We used data from the National
      Birth Defects Prevention Study, an ongoing multicenter, population-based, case
      control study. Mothers of cases and controls were interviewed by telephone.
      Analyses included 255 anencephaly, 577 spina bifida, 648 gastroschisis cases, and
      5587 controls with deliveries from 1999 to 2005. After subtracting birth weight,
      the associations of total and average weekly weight gain (kg) with each phenotype
      were estimated, stratified by gestational age (<37 vs. >=37 weeks) and adjusted
      for relevant covariates. RESULTS: Among deliveries <37 weeks gestation, mothers
      of infants with anencephaly and spina bifida had lower weight gains compared to
      control mothers; no association between weight gains and gastroschisis was
      observed. Among deliveries >=37 weeks, mothers of infants with anencephaly had
      lower weight gains during pregnancy; a similar association was not observed for
      spina bifida; mothers of infants with gastroschisis were twice as likely to have
      weight gains in the highest quartile. Stratification by maternal age
      (gastroschisis) or body mass index (BMI) or race/ethnicity (all phenotypes) did
      not alter odds ratio estimates. CONCLUSION: Altered weight gain during pregnancy
      may be a consequence of carrying an NTD/gastroschisis affected fetus or a marker
      for underlying factors common to the etiology of these birth defects. It is
      possible that whatever mechanisms influence weight gain may also influence the
      development of NTDs and gastroschisis, but in opposite directions.

PMID- 22847947
TI  - DSM-IV-defined anorexia nervosa versus subthreshold anorexia nervosa (EDNOS-AN).
AB  - OBJECTIVES: Eating disorder not otherwise specified (EDNOS) is the most prevalent
      eating disorder, yet its heterogeneity begs less reliance on this broad
      diagnostic category. The purpose of this study was to compare women with anorexia
      nervosa (AN) and EDNOS, AN type (EDNOS-AN) from a multisite study on eating
      related and general psychopathology measures. METHODS: One hundred eighteen
      participants (n = 59 with DSM-IV AN, n = 59 with EDNOS-AN) completed structured
      interviews, questionnaires and a physical examination at baseline. In addition,
      participants carried a handheld palm pilot computer for 2 weeks to provide
      ecological momentary assessment (EMA) information about mood and eating disorder
      behaviours. RESULTS: No significant differences between AN and EDNOS-AN were
      found on the self-report and interview measures, or on the EMA mood assessments.
      The only differences to emerge were that participants with AN reported higher
      rates of binge eating and purging on EMA compared with those with EDNOS-AN,
      whereas EDNOS-AN reported higher rates of checking thighs and joints on EMA
      compared with those with AN. For the physiological parameters, AN presented with
      lower white blood cell counts compared with EDNOS-AN. CONCLUSIONS: Findings
      highlight the clinical significance of EDNOS-AN and support a closer look at the
      definition of AN as proposed by the Diagnostic and Statistical Manual of Mental
      Disorders, 5th Edition.

PMID- 22847949
TI  - Solution and solid-state dynamics of metal-coordinated white phosphorus.
AB  - The dynamic behavior in solution of eight mono-hapto tetraphosphorus transition
      metal-complexes, trans-[Ru(dppm)(2)(H)(eta(1)-P(4))]BF(4) ([1]BF(4)), trans
      [Ru(dppe)(2)(H)(eta(1)-P(4))]BF(4) ([2]BF(4)), [CpRu(PPh(3))(2)(eta(1)
      P(4))]PF(6) ([3]PF(6)), [CpOs(PPh(3))(2)(eta(1)-P(4))]PF(6) ([4]PF(6)),
      [Cp*Ru(PPh(3))(2)(eta(1)-P(4))]PF(6) ([5]PF(6)), [Cp*Ru(dppe)(eta(1)-P(4))]PF(6)
      ([6]PF(6)), [Cp*Fe(dppe)(eta(1)-P(4))]PF(6) ([7]PF(6)),
      [(triphos)Re(CO)(2)(eta(1)-P(4))]OTf ([8]OTf), and of three bimetallic
      Ru(MU,eta(1:2)-P(4))Pt species [{Ru(dppm)(2)(H)}(MU,eta(1:2)
      P(4)){Pt(PPh(3))(2)}]BF(4) ([1-Pt]BF(4)), [{Ru(dppe)(2)(H)}(MU,eta(1:2)
      P(4)){Pt(PPh(3))(2)}]BF(4) ([2-Pt]BF(4)), [{CpRu(PPh(3))(2))}(MU,eta(1:2)
      P(4)){Pt(PPh(3))(2)}]BF(4) ([3-Pt]BF(4)), [dppm=bis(diphenylphosphanyl)methane;
      dppe=1,2-bis(diphenylphosphanyl)ethane; triphos=1,1,1
      tris(diphenylphosphanylmethyl)ethane; Cp=eta(5)-C(5)H(5); Cp*=eta(5)-C(5)Me(5) ]
      was studied by variable-temperature (VT) NMR and (31)P{(1)H} exchange
      spectroscopy (EXSY). For most of the mononuclear species, NMR spectroscopy
      allowed to ascertain that the metal-coordinated P(4) molecule experiences a
      dynamic process consisting, apart from the free rotation about the M-P(4) axis,
      in a tumbling movement of the P(4) cage while remaining chemically coordinated to
      the central metal. EXSY and VT (31)P NMR experiments showed that also the
      binuclear complex cations [1-Pt](+)-[3-Pt](+) are subjected to molecular motions
      featured by the shift of each metal from one P to an adjacent one of the P(4)
      moiety. The relative mobility of the metal fragments (Ru vs. Pt) was found to
      depend on the co-ligands of the binuclear complexes. For complexes [2]BF(4) and
      [3]PF(6), MAS, (31)P NMR experiments revealed that the dynamic processes observed
      in solution (i.e., rotation and tumbling) may take place also in the solid state.
      The activation parameters for the dynamic processes of complexes 1(+), 2(+),
      3(+), 4(+), 6(+), 8(+) in solution, as well as the X-ray structures of 2(+),
      3(+), 5(+), 6(+) are also reported. The data collected suggest that metal
      coordinated P(4) should not be considered as a static ligand in solution and in
      the solid state.

PMID- 22847950
TI  - Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular
      cytogenetic characterization.
AB  - We describe 19 unrelated individuals with submicroscopic deletions involving
      10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our
      knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion
      have been reported to date; however, only limited clinical information is
      available for these probands and the deleted region has not been molecularly
      mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals
      described in this study. Common features among these 12 individuals include:
      cognitive/behavioral/developmental differences (11/11), speech delay/language
      disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia
      (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed
      for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the
      probands, not maternally inherited in one proband and inherited from an
      apparently affected mother in one proband. Molecular mapping of the 19
      individuals reported in this study has identified two genes, ZMYND11 (OMIM
      608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3
      which are most commonly deleted. Although no single gene has been identified
      which is deleted in all 19 individuals studied, the deleted region in all but one
      individual includes ZMYND11 and the deleted region in all but one other
      individual includes DIP2C. There is not a clearly identifiable phenotypic
      difference between these two individuals and the size of the deleted region does
      not generally predict clinical features. Little is currently known about these
      genes complicating a direct genotype/phenotype correlation at this time. These
      data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to
      the clinical features associated with 10p15 deletions in probands described in
      this study.

PMID- 22847948
TI  - Is social categorization based on relational ingroup/outgroup opposition? A meta
      analysis.
AB  - Social categorization is known to be an important part of social cognition. The
      categorizations we use, despite their multitude, frequently take the form of the
      general ingroup/outgroup distinction. A meta-analysis of 33 fMRI studies,
      reporting selective activations to various social groups, was used to identify
      common neural structures responsible for relational representation of social
      structure. Activation Likelihood Estimation (ALE) analysis revealed areas in
      bilateral amygdala, cingulate gyrus, fusiform gyrus, right TPJ and right insula
      as implementing various aspects of social categorization. Activation of amygdala
      can be associated with modulation of behavioral response to subjectively
      significant stimuli. A more ventral part of anterior cingulate cortex (ACC) can
      be associated with self-referential reasoning about ingroup members while a more
      dorsal part of ACC is involved in the regulation of emotions toward outgroup
      members. Right insula can be engaged in the modulation of outgroup avoidance
      behavior. Fusiform gyrus (FG) appears to be directly involved in social
      categorization process via top-down modulation of social perception. Yet it is
      difficult to associate any of the revealed clusters with the relational
      ingroup/outgroup structure. 

PMID- 22847953
TI  - Analysis of regional recurrence after negative sentinel lymph node biopsy for
      head and neck melanoma.
AB  - BACKGROUND: The head and neck have a rich lymphatic drainage and complex anatomy,
      which complicate sentinel lymph node (SLN) biopsy for melanoma. The incidence of
      regional recurrence after a negative SLN biopsy has been shown to be higher than
      that at other sites. Compounding factors in this scenario were analyzed to
      determine their impact on both SLN status and survival. METHODS: A retrospective
      review of a prospective database of 315 patients who underwent SLN biopsy for
      head and neck melanoma from 1994 to 2009 was performed. A false-negative SLN
      biopsy was defined as a regional recurrence in a previously mapped nodal basin.
      RESULTS: In all, 267 patients (84.8%) were SLN negative (SLN-) and 48 patients
      (15.2%) were SLN positive (SLN+). The false-negative SLN biopsy occurred in 17
      patients (6.4%). The mean follow-up was 37.6 months (3-152 months). The false
      negative SLN and SLN+ patients were similar with respect to patient age and sex
      and primary melanoma tumor thickness and ulceration. The site of the primary
      melanoma and the lymphatic drainage patterns did not influence the false-negative
      biopsy rate. The mean survival was SLN- 119.3 months (95% confidence interval
      [CI], 106.1-132.5, p < .001), SLN+ 73.4 months (95% CI, 52.3-94.4), and the false
      negative SLN 70.7 months (95% CI, 54.2-87.1). CONCLUSIONS: The risk of a false
      negative SLN biopsy in head and neck melanoma is independent of primary site and
      lymphatic drainage pattern. Patients with head and neck melanoma who have a
      regional recurrence after a negative SLN biopsy do not have a worse survival than
      that of patients who are initially SLN positive.

PMID- 22847951
TI  - Chitosan dressing promotes healing in third degree burns in mice: gene expression
      analysis shows biphasic effects for rapid tissue regeneration and decreased
      fibrotic signaling.
AB  - Burns are a significant health challenge and healing can result in scar
      formation. Chitosan, a derivative of chitin, has been used to promote wound
      healing. In this study we used gene expression profiling in a mouse model of full
      thickness cutaneous burn to assess the benefits of treating with a chitosan
      lactate dressing. Three days after wounding mice treated with chitosan showed
      increased expression of genes associated with formation of granulation tissue. At
      a later time point, seven days after wounding, genes that initially showed
      increased expression were now down-regulated, and there was increased expression
      of genes involved in remodeling suggesting that the chitosan treatment results in
      accelerated healing. Quantitative RT-PCR showed modulated mRNA levels for
      TGFbeta1 by the chitosan dressing. TGFbeta1 initially promotes healing but
      extended activity can result in scarring. Importantly we found that expression
      was elevated at day three, but decreased at day seven suggesting that chitosan
      treatment will not result in scar formation, and may even be beneficial in
      preventing scar formation. Additionally, the biphasic regulation of expression of
      TGFbeta1 could be a powerful biomarker for future studies of the wound-healing
      potential of chitosan based and other treatments for burn wounds.

PMID- 22847955
TI  - Counseling about risks of congenital anomalies from prescription opioids.
AB  - The use of prescription opioids is becoming an increasing problem among women of
      reproductive age. More than half of pregnancies are unintended; therefore, many
      first-trimester exposures to opioids occur before pregnancy confirmation. Studies
      are limited about the fetal risks to opioid exposure in early pregnancy. One
      large study demonstrated an increased risk of certain heart defects and spina
      bifida with first-trimester exposure to opioids. It is important to counsel women
      whose fetuses were exposed to opioids in early pregnancy about the potential
      risks, encourage them to cease using opioids or seek alternative treatments when
      appropriate, and use the lowest effective dose when opioid treatment is to be
      continued. It is also valuable to screen for anatomic abnormalities such as
      neural tube and cardiac defects with available maternal serum testing and
      ultrasound imaging in the early second trimester. Birth Defects Research (Part A)
      94:620-625, 2012. (c) 2012 Wiley Periodicals, Inc.

PMID- 22847954
TI  - DNA methylation alterations in response to pesticide exposure in vitro.
AB  - Although pesticides are subject to extensive carcinogenicity testing before
      regulatory approval, pesticide exposure has repeatedly been associated with
      various cancers. This suggests that pesticides may cause cancer via
      nonmutagenicity mechanisms. The present study provides evidence to support the
      hypothesis that pesticide-induced cancer may be mediated in part by epigenetic
      mechanisms. We examined whether exposure to seven commonly used pesticides (i.e.,
      fonofos, parathion, terbufos, chlorpyrifos, diazinon, malathion, and phorate)
      induces DNA methylation alterations in vitro. We conducted genome-wide DNA
      methylation analyses on DNA samples obtained from the human hematopoietic K562
      cell line exposed to ethanol (control) and several organophosphate pesticides
      (OPs) using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian-adjusted
      t-tests were used to identify differentially methylated gene promoter CpG sites.
      In this report, we present our results on three pesticides (fonofos, parathion,
      and terbufos) that clustered together based on principle component analysis and
      hierarchical clustering. These three pesticides induced similar methylation
      changes in the promoter regions of 712 genes, while also exhibiting their own OP
      specific methylation alterations. Functional analysis of methylation changes
      specific to each OP, or common to all three OPs, revealed that differential
      methylation was associated with numerous genes that are involved in
      carcinogenesis-related processes. Our results provide experimental evidence that
      pesticides may modify gene promoter DNA methylation levels, suggesting that
      epigenetic mechanisms may contribute to pesticide-induced carcinogenesis. Further
      studies in other cell types and human samples are required, as well as
      determining the impact of these methylation changes on gene expression.

PMID- 22847956
TI  - Evaluation of flavonoid and resveratrol chemical libraries reveals abyssinone II
      as a promising antibacterial lead.
AB  - Lead on! In the course of screening flavonoid and resveratrol libraries,
      abyssinone II, a naturally occurring prenylated flavonoid, was found to exhibit
      relatively good antitubercular and antibacterial activity. Preliminary
      mechanistic studies revealed that abyssinone II hyperpolarizes the bacterial
      membrane potential and inhibits the biosynthesis of key cellular macromolecules
      (DNA, RNA, and protein).

PMID- 22847957
TI  - Serotonin transporter length polymorphism, childhood maltreatment, and chronic
      depression: a specific gene-environment interaction.
AB  - BACKGROUND: Key questions about the interaction between the serotonin transporter
      length polymorphism (5-HTTLPR) and stress in the etiology of depression remain
      unresolved. We test the hypotheses that the interaction is restricted to
      childhood maltreatment (as opposed to stressful events in adulthood), and leads
      to chronic depressive episodes (as opposed to any onset of depression), using
      gold-standard assessments of childhood maltreatment, severe life events, chronic
      depression, and new depressive onsets. METHOD: In a risk-enriched sample of 273
      unrelated women, childhood maltreatment was retrospectively assessed with the
      Childhood Experience of Care and Abuse (CECA) interview and 5-HTTLPR was
      genotyped. A subset of 220 women was followed prospectively for 12 months with
      life events assessed with the Life Events and Difficulties (LEDS) interview. Any
      chronic episode of depression (12 months or longer) during adulthood and onset of
      a major depressive episode during a 12-month follow-up were established with the
      Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. RESULTS:
      The short alleles of 5-HTTLPR moderated the relationship between childhood
      maltreatment and chronic depression in adulthood, reflected in a significant gene
      environment interaction (RD = 0.226, 95% CI: 0.076-0.376, P = .0032). 5-HTTLPR
      did not moderate the effects of either childhood maltreatment or severe life
      events on new depressive onsets. CONCLUSIONS: The short variant of the serotonin
      transporter gene specifically sensitizes to the effect of early-life experience
      of abuse or neglect on whether an adult depressive episode takes a chronic
      course. This interaction may be responsible for a substantial proportion of cases
      of chronic depression in the general population.

PMID- 22847958
TI  - Dialane with a redox-active bis-amido ligand: unique reactivity towards alkynes.
AB  - The treatment of 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-bian)
      with one equivalent of AlCl(3) and three equivalents of sodium in toluene at 110 
      degrees C produced a stable dialane, (dpp-bian)Al-Al(dpp-bian) (1). The reaction
      of compound 1 with pyridine gave Lewis-acid-base adduct (dpp-bian)(Py)Al
      Al(Py)(dpp-bian) (2). Acetylene and phenylacetylene reacted with compound 1 to
      give cycloaddition products [dpp-bian(R(1)R(2))]Al-Al[(R(2)R(1))dpp-bian] (3:
      R(1)=R(2)=CH; 4: R(1)=CH, R(2)=CPh). These addition reactions occur across Al-N-C
      moieties and result in the formation of new C-C and C-Al bonds. At elevated
      temperatures, compound 4 rearranges into complex 5, which consists of a radical
      anionic dpp-bian ligand and two bridging alken-1,2-diyl moieties, (dpp
      bian)Al(HCCPh)(2)Al(dpp-bian). This transformation is accompanied by cleavage of
      the dpp-bian-ligand-alkyne C-C bond, as well as of the Al-Al bond. In contrast to
      its analogous gallium complex, compound 1 is reactive towards internal alkynes.
      In the reaction of compound 1 with PhC=CMe, besides symmetrical addition product
      [dpp-bian(R(1)R(2))]Al-Al[(R(2)R(1))dpp-bian] (R(1)=CMe, R(2)=CPh; 6), monoadduct
      [dpp-bian(R(1)R(2))]Al-Al(dpp-bian) (R(1)=CMe, R(2)=CPh; 7) was also isolated.
      Complexes 1-7 were characterized by IR, (1)H NMR (1-4), and electronic absorption
      spectroscopy (3-5); the molecular structures of compounds 1-7 were determined by
      single-crystal X-ray diffraction.

PMID- 22847959
TI  - In vitro drug release studies from organoclay/poly(dimethyl siloxane)
      nanocomposite matrices.
AB  - Silicone elastomers are versatile biomaterials and have been used for fabrication
      of drug release systems, usually incorporating lipophilic drugs. However,
      attempts have been made to extend the use of these biomaterials to the delivery
      of hydrophilic drugs. Furthermore, the need to improve mechanical properties of
      silicones led, among others, to the incorporation of organoclay nanoparticles
      and, therefore, has introduced some new parameters to be investigated regarding
      their effect on the release profile. In this work, the delivery of 2-methyl-5
      nitroimidazole-1-ethanol (metronidazole) from nanocomposites with silicone matrix
      based on condensation cured elastomers with different molecular weights was
      investigated in various surrounding liquids. The results showed that
      incorporation of organic modified montmorillonite (OMMT) generally decreases the
      drug release rate and restricts the initial burst effect. Interestingly, OMMT
      concentrations of 2 phr in low MW silicone systems seem to enhance drug release
      and, independently of interpretation, it might indicate a route for the
      adjustment of diffusivity through the nanoclay concentration. Maximum drug
      release rates can rather be achieved with low MW PDMS than with the higher MW
      elastomers.

PMID- 22847961
TI  - Microcin C and albomycin analogues with aryl-tetrazole substituents as nucleobase
      isosters are selective inhibitors of bacterial aminoacyl tRNA synthetases but
      lack efficient uptake.
AB  - In 1998, Cubist Pharmaceuticals patented a series of aminoacyl tRNA synthetase
      (aaRS) inhibitors based on aminoacyl sulfamoyladenosines (aaSAs), in which the
      adenine was substituted by aryl-tetrazole moieties linked to the ribose fragment
      by a two-carbon spacer. Although potent and specific inhibitors of bacterial
      IleRS, these compounds did not prove successful in vivo due to low cell
      permeability and strong binding to serum albumin. In this work, we attempted to
      improve these compounds by combining them with microcin C (McC) or albomycin
      (i.e., siderophore-drug conjugate (SDC)) transport modules. We found that aryl
      tetrazole variants of McC and albomycin still lacked antibacterial activity.
      However, these compounds were readily processed by E. coli aminopeptidases with
      the release of toxic aaRS inhibitors. Hence, the lack of activity in whole-cell
      assays was due to an inability of the new compounds to be taken up by the cells,
      thus indicating that the nucleotide moieties of McC and albomycin strongly
      contribute to facilitated transport of these compounds inside the cell.

PMID- 22847962
TI  - "Mystic" transient recurrent nerve palsy after thyroid surgery.
AB  - BACKGROUND: The mechanism of transient recurrent laryngeal nerve (RLN) palsy
      remains unclear. METHODS: Samples were harvested from the RLN adjacent thyroid
      capsule and perineural fascia during 223 lobectomies and 89 RLNs from cadavers
      were used for histologic and immunohistologic evaluation. Intraoperative
      chromoendoscopic features of the RLN were compared with postoperative ear, nose,
      and throat examinations. RESULTS: Those nerves that macroscopically seem to be
      single-branched (35 of 89 = 39.3%), microscopically consist of multiple fascicles
      in most of the cases (23 of 35 = 65.7%), resembling a plexus more than a single
      cord. Chronic lymphocytic infiltration of the thyroid capsule adjacent to the RLN
      was present in 29% (65 of 223) of the cases. The perineural fascia showed
      lymphocytic (18 of 223 = 8.1%) or granulocytic (7 of 223 = 3.1%) infiltration.
      CONCLUSIONS: The origin of transient RLN palsy is multifactorial: plexus shaped
      microscopic nerve structure with or without branches, frame-like adventitial
      tissue, variable epineurium, inflammatory changes that involve not only the
      thyroid capsule but the perineural fascia, resultant nerve edema, and diffuse
      microhemorrhages by injury of fragile capillaries.

PMID- 22847960
TI  - Modulating patterned adhesion and repulsion of HEK 293 cells on microengineered
      parylene-C/SiO(2)  substrates.
AB  - This article describes high resolution patterning of HEK 293 cells on a construct
      of micropatterned parylene-C and silicon dioxide. Photolithographic patterning of
      parylene-C on silicon dioxide is an established and consistent process.
      Activation of patterns by immersion in serum has previously enabled patterning of
      murine hippocampal neurons and glia, as well as the human hNT cell line. Adapting
      this protocol we now illustrate high resolution patterning of the HEK 293 cell
      line. We explore hypotheses that patterning is mediated by transmembrane integrin
      interactions with differentially absorbed serum proteins, and also by etching the
      surface substrate with piranha solution. Using rationalized protein activation
      solutions in place of serum, we show that cell patterning can be modulated or
      even inverted. These cell-patterning findings assist our wider goal of
      engineering and interfacing functional neuronal networks via a silicon
      semiconductor platform.

PMID- 22847963
TI  - Development and homeostasis of "resident" myeloid cells: the case of the
      microglia.
AB  - Microglia, macrophages of the central nervous system, play an important role in
      brain homeostasis. Their origin has been unclear. Recent fate-mapping experiments
      have established that microglia mostly originate from Myb-independent, FLT3
      independent, but PU.1-dependent precursors that express the CSF1-receptor at E8.5
      of embryonic development. These precursors are presumably located in the yolk sac
      (YS) at this time before invading the embryo between E9.5 and E10.5 and
      colonizing the fetal liver. Indeed, the E14.5 fetal liver contains a large
      population of Myb-independent YS-derived myeloid cells. This myeloid lineage is
      distinct from hematopoietic stem cells (HSCs), which require the transcription
      factor Myb for their development and maintenance. This "yolky" beginning and the
      independence from conventional HSCs are not unique to microglia. Indeed, several
      other populations of F4/80-positive macrophages develop also from YS Myb
      independent precursors, such as Kupffer cells in the liver, Langerhans cells in
      the epidermis, and macrophages in the spleen, kidney, pancreas, and lung.
      Importantly, microglia and the other Myb-independent macrophages persist, at
      least in part, in adult mice and likely self-renew within their respective
      tissues of residence, independently of bone marrow HSCs. This suggests the
      existence of tissue resident macrophage "stem cells" within tissues such as the
      brain, and opens a new era for the molecular and cellular understanding of
      myeloid cells responses during acute and chronic inflammation.

PMID- 22847965
TI  - Palliative care training substandard.

PMID- 22847966
TI  - Heavy hitting: concussions and safety law.

PMID- 22847964
TI  - Adverse events among children in Canadian hospitals: the Canadian Paediatric
      Adverse Events Study.
AB  - BACKGROUND: Limited data are available on adverse events among children admitted
      to hospital. The Canadian Paediatric Adverse Events Study was done to describe
      the epidemiology of adverse events among children in hospital in Canada. METHODS:
      We performed a 2-stage medical record review at 8 academic pediatric centres and
      14 community hospitals in Canada. We reviewed charts from patients admitted from
      April 2008 through March 2009, evenly distributed across 4 age groups (0 to 28 d;
      29 to 365 d; > 1 to 5 yr and > 5 to 18 yr). In stage 1, nurses and health records
      personnel who had received training in the use of the Canadian Paediatric Trigger
      Tool reviewed medical records to detect triggers for possible adverse events. In
      stage 2, physicians reviewed the charts identified as having triggers and
      described the adverse events. RESULTS: A total of 3669 children were admitted to
      hospital during the study period. The weighted rate of adverse events was 9.2%.
      Adverse events were more frequent in academic pediatric centres than in community
      hospitals (adjusted odds ratio [OR] 2.98, 95% confidence interval [CI] 1.65
      5.39). The incidence of preventable adverse events was not significantly
      different between types of hospital, but nonpreventable adverse events were more
      common in academic pediatric centres (adjusted OR 4.39, 95% CI 2.08-9.27).
      Surgical events predominated overall and occurred more frequently in academic
      pediatric centres than in community hospitals (37.2% v. 21.5%, relative risk [RR]
      1.7, 95% CI 1.0-3.1), whereas events associated with diagnostic errors were
      significantly less frequent (11.1% v. 23.1%, RR 0.5, 95% CI 0.2-0.9).
      INTERPRETATION: More children have adverse events in academic pediatric centres
      than in community hospitals; however, adverse events in the former are less
      likely to be preventable. There are many opportunities to reduce harm affecting
      children in hospital in Canada, particularly related to surgery, intensive care
      and diagnostic error.

PMID- 22847967
TI  - Professionalism: assessing physician behaviour.

PMID- 22847970
TI  - Professionalism: how payment models affect physician behaviour.

PMID- 22847969
TI  - Training family physicians in shared decision-making to reduce the overuse of
      antibiotics in acute respiratory infections: a cluster randomized trial.
AB  - BACKGROUND: Few interventions have proven effective in reducing the overuse of
      antibiotics for acute respiratory infections. We evaluated the effect of
      DECISION+2, a shared decision-making training program, on the percentage of
      patients who decided to take antibiotics after consultation with a physician or
      resident. METHODS: We performed a randomized trial, clustered at the level of
      family practice teaching unit, with 2 study arms: DECISION+2 and control. The
      DECISION+2 training program included a 2-hour online tutorial followed by a 2
      hour interactive seminar about shared decision-making. The primary outcome was
      the proportion of patients who decided to use antibiotics immediately after
      consultation. We also recorded patients' perception that shared decision-making
      had occurred. Two weeks after the initial consultation, we assessed patients'
      adherence to the decision, repeat consultation, decisional regret and quality of
      life. RESULTS: We compared outcomes among 181 patients who consulted 77
      physicians in 5 family practice teaching units in the DECISION+2 group, and 178
      patients who consulted 72 physicians in 4 family practice teaching units in the
      control group. The percentage of patients who decided to use antibiotics after
      consultation was 52.2% in the control group and 27.2% in the DECISION+2 group
      (absolute difference 25.0%, adjusted relative risk 0.48, 95% confidence interval
      0.34-0.68). DECISION+2 was associated with patients taking a more active role in
      decision-making (Z = 3.9, p < 0.001). Patient outcomes 2 weeks after consultation
      were similar in both groups. INTERPRETATION: The shared decision-making program
      DECISION+2 enhanced patient participation in decision-making and led to fewer
      patients deciding to use antibiotics for acute respiratory infections. This
      reduction did not have a negative effect on patient outcomes 2 weeks after
      consultation. ClinicalTrials.gov trial register no. NCT01116076.

PMID- 22847971
TI  - Cannon waves in atrioventricular nodal re-entry tachycardia.

PMID- 22847972
TI  - OTIS special issue preface.

PMID- 22847973
TI  - Synthesis of stable genipin derivatives and studies of their neuroprotective
      activity in PC12 cells.
AB  - Modifications at C1, C7, C8, and C10 of genipin were conducted, and the
      neurotrophic effects of all derivatives were studied. Genipin derivatives 1-4
      were obtained in mild to high yield. Compounds 1 and 4 are more stable than
      genipin if exposed to nucleophiles. All the derivatives display higher
      neurotrophic activities than genipin. Compound 4 is the most active, with the
      least optimal dose. Both genipin and 4 up-regulated the activity of nNOS in PC12
      cells. The effect of 4 is inhibited not only by 7-NI, a specific inhibitor of
      nNOS, but also by L-NIO, a specific inhibitor of eNOS; in the case of genipin,
      its effect is only inhibited by 7-NI. All the results indicate that 4 is a
      promising lead compound for the development of new drugs in the treatment of
      neurodegenerative diseases with the ability to address multiple drug targets.

PMID- 22847974
TI  - Comparison of three humanized mouse models for adoptive T cell transfer.
AB  - BACKGROUND: Humanized mouse models for adoptive T cell transfer are important for
      preclinical efficacy and toxicity studies. However, common xenograft models using
      immunodeficient mice have so far failed to efficiently support the homing of
      human T cells to secondary lymphoid tissues. METHODS: We established a new mouse
      model for the adoptive transfer of genetically-modified (gm) T cells using
      conditioned BALB/c mice. Conditioning involved cyclophosphamide injections,
      lethal irradiation and radioprotection with bone marrow from immunodeficient
      mice. We compared repopulation kinetics and the quality of grafts in these
      modified Trimera (mT3) mice with immunodeficient BALB/c Rag2(-/-) interleukin
      (IL)2 receptor gamma (rg) knockout (DKO) and NOD/LtSz-scid IL2rg(-/-) (NSG)
      recipient mouse strains. RESULTS: DKO mice showed only marginal engraftment until
      onset of graft-versus-host disease, whereas mT3 and NSG were repopulated with
      comparable kinetics. However, T cell repertoire and human cytokine profiles
      suggest a xenoreactivity-driven gm T cell expansion in mT3 mice, whereas NSG mice
      were characterized by an initial homeostatic proliferation. Morphological
      analysis revealed high levels of human gm T cell infiltration in the spleen and
      liver of all three mouse strains. However, mT3 mice provided the strongest homing
      of human gm T cells to mucosal sites. Additionally, mT3 mice were the only model
      with macroscopically visible superficial inguinal lymph nodes. These lymph nodes
      strongly supported the homing of gm T cells. CONCLUSIONS: In the present study,
      we give proof-of-concept that wild-type mice can accept gm T cell grafts while
      providing secondary lymphoid structures. Despite limitations, mT3 mice are a
      valid alternative for applications that specifically rely on improved secondary
      lymphoid structures.

PMID- 22847975
TI  - Proteomics tackling schizophrenia as a pathway disorder.

PMID- 22847976
TI  - Anion sensing in aqueous media by photo-active transition-metal bipyridyl
      rotaxanes.
AB  - A chloride anion templation methodology is utilized in the construction of novel
      transition-metal rhenium(I) and ruthenium(II) bipyridyl appended [2]rotaxanes.
      (1)H NMR spectroscopic titrations reveal the ability of the rotaxanes to
      selectively bind chloride over the more basic oxoanions, with the ruthenium(II)
      bipyridyl appended rotaxane strongly binding chloride in 30% water. Photophysical
      investigations demonstrate the ability of the rotaxanes to sense anions in
      aqueous media, with chloride being selectively complexed, in general agreement
      with NMR spectroscopy determined anion binding data.

PMID- 22847977
TI  - Lithium-sulfur batteries based on nitrogen-doped carbon and an ionic-liquid
      electrolyte.
AB  - Nitrogen-doped mesoporous carbon (NC) and sulfur were used to prepare an NC/S
      composite cathode, which was evaluated in an ionic-liquid electrolyte of 0.5 M
      lithium bis(trifluoromethane sulfonyl)imide (LiTFSI) in methylpropylpyrrolidinium
      bis(trifluoromethane sulfonyl)imide ([MPPY][TFSI]) by cyclic voltammetry (CV),
      electrochemical impedance spectroscopy (EIS), and cycle testing. To facilitate
      the comparison, a C/S composite based on activated carbon (AC) without nitrogen
      doping was also fabricated under the same conditions. Compared with the AC/S
      composite, the NC/S composite showed enhanced activity toward sulfur reduction,
      as evidenced by the lower onset sulfur reduction potential, higher redox current
      density in the CV test, and faster charge-transfer kinetics, as indicated by EIS
      measurements. At room temperature under a current density of 84 mA g(-1) (C/20),
      the battery based on the NC/S composite exhibited a higher discharge potential
      and an initial capacity of 1420 mAh g(-1), whereas the battery based on the AC/S
      composite showed a lower discharge potential and an initial capacity of 1120 mAh
      g(-1). Both batteries showed similar capacity fading with cycling due to the
      intrinsic polysulfide solubility and the polysulfide shuttle mechanism; capacity
      fading can be improved by further cathode modification.

PMID- 22847978
TI  - Surface-bound orientated Jagged-1 enhances osteogenic differentiation of human
      periodontal ligament-derived mesenchymal stem cells.
AB  - Notch signaling plays critical roles in various cell types by regulating cell
      fate determination and differentiation. Here, we investigated the ability to
      control differentiation of human periodontal ligament derived mesenchymal stem
      cells using modified surfaces containing the affinity immobilized Notch ligand,
      Jagged-1. After seeding human periodontal ligament derived mesenchymal stem cells
      (HPDLs) on Jagged-1 modified surfaces, expression of Notch signaling target
      genes, Hes-1 and Hey-1, was higher than those exposed to soluble Jagged-1 or
      control surfaces. Upregulation of Notch signaling target genes was attenuated
      after treatment with the gamma secretase inhibitor. Upon seeding the cells on
      Jagged-1 immobilized surface and maintained in osteogenic medium, alkaline
      phosphatase enzymatic activity and mineralization as well as mRNA expression of
      alkaline phosphatase (ALP), collagen type I (COL I) and osteopontin (OPN) were
      significantly increased compared to those of controls. However, osteocalcin (OCN)
      mRNA expression level was decreased when cells were exposed to Jagged-1 modified
      surfaces. HPDLs on Jagged-1 modified surfaces expressed lower TWIST2 mRNA levels
      than the control, suggesting that the mechanism whereby Jagged-1 enhances
      osteogenic differentiation of HPDLs may occur through Notch signaling and TWIST
      regulation. In summary, an alteration of biomaterial interface using Notch
      ligands illustrates a promising system to control HPDLs differentiation toward
      osteogenic lineage.

PMID- 22847979
TI  - Bone healing response to a synthetic calcium sulfate/beta-tricalcium phosphate
      graft material in a sheep vertebral body defect model.
AB  - The introduction of a material able to promote osteogenesis and remodelling
      activity in a clinically relevant time frame in vertebroplasty and kyphoplasty
      procedures may have patient benefit. We report the in-vivo performance of a
      biphasic synthetic bone graft material (Genex Paste, Biocomposites, UK) [test
      material], composed of calcium sulfate and beta-tricalcium phosphate, implanted
      into a sheep vertebral defect model. Cavities drilled into 4 adjacent vertebrae
      (L2 to L5) of 24 skeletally mature sheep were; (1) filled with the test material;
      (2) filled with commercially available polymethylmethacrylate [PMMA] cement; (3)
      remained empty [sham]. Analysis was performed immediately after implantation and
      at 8, 16, and 36 weeks post implantation. Sites were evaluated for bone growth
      with microCT analysis, histological examination, and mechanical testing under
      compression. The test material exhibited an improved tissue response over the
      PMMA, indicating a superior biological tolerance. MicroCT and histology indicated
      marked osteoregenerative capacity of the test material when compared with sham
      and the PMMA. The percentage of new bone formation was higher for the test
      material than sham at 16 and 36 weeks post implantation, with bone regeneration
      almost complete at 36 weeks in this group. Resorption of test material and the
      integration into new bone tissue were demonstrated.

PMID- 22847980
TI  - A new angle to mandibular reconstruction: the scapular tip free flap.
AB  - BACKGROUND: The purpose of this study was to review our experience with the
      scapular tip free flap for mandibular reconstruction, describe the surgical
      approach, and highlight specific clinical applications. METHODS: A retrospective
      review of all patients undergoing oromandibular reconstruction using a scapular
      tip free flap at the London Health Sciences Centre was undertaken. Patient
      demographics, surgical data, and early outcomes were collated. RESULTS: Twenty
      patients were identified. The majority involved mandibular angle and short
      segment defects (16 of 20). Average length of the segmental defect was 6.2 cm
      with the longest measuring 8 cm. A single patient required an osteotomy. Six were
      revision cases. No vein grafts were required. One complete flap failure occurred.
      CONCLUSIONS: The natural scapular angle makes the scapular tip flap ideal for
      mandibular angle reconstruction. Short bone segments can be harvested with little
      donor-site morbidity. The long pedicle length may obviate vein grafts.

PMID- 22847982
TI  - A highly cross-linked polymeric binder for high-performance silicon negative
      electrodes in lithium ion batteries.

PMID- 22847981
TI  - A phase I trial and pharmacokinetic study of a 24-hour infusion of trabectedin
      (Yondelis(r), ET-743) in children and adolescents with relapsed or refractory
      solid tumors.
AB  - BACKGROUND: The objectives of this phase I study were to determine the maximum
      tolerated dose (MTD), toxicity profile, and pharmacokinetics of a 24-hour
      continuous intravenous infusion of trabectedin administered to children and
      adolescents with refractory or relapsed solid tumors. PROCEDURE: Patients between
      the ages of 4 and 16 years old with refractory solid tumors received trabectedin
      as a 24-hour infusion every 21 days. Dexamethasone and prophylactic growth factor
      support were administered with each cycle. Pharmacokinetic studies were conducted
      during cycle 1. RESULTS: Patients (n = 12) median (range) age 14.5 (8-16) years
      received trabectedin at 1.1 (n = 3), 1.5 (n = 6), or 1.7 (n = 3) mg/m(2). At the
      1.5 mg/m(2) dose level, one patient had dose limiting anorexia and fatigue. At
      1.7 mg/m(2), two patients experienced dose limiting toxicity, dehydration, and
      gamma-glutamyl transpeptidase elevation. Non-dose limiting toxicities included
      elevated serum transaminases, myelosuppression, nausea, emesis, and fatigue.
      Plasma pharmacokinetic parameters were similar to historical data in adults. One
      partial response was observed in a patient with neuroendocrine carcinoma. Stable
      disease (>=6 cycles) was achieved in three patients (osteosarcoma n = 2,
      desmoplastic small round cell tumor n = 1). CONCLUSIONS: The MTD of trabectedin
      in pediatric patients with refractory solid tumors is 1.5 mg/m(2) IV over 24
      hours every 21 days. Dexamethasone to ameliorate hepatic toxicity and
      prophylactic growth factor support are required.

PMID- 22847983
TI  - Systemic mastocytosis associated with t(8;21) acute myeloid leukemia in a child:
      detection of the D816A mutation of KIT.
AB  - Systemic mastocytosis (SM) associated with t(8;21) acute myeloid leukemia (AML)
      is very rare, and the D816 mutation of the KIT gene has previously been detected
      only in adult patients. We herein report the case of a 5-year-old female
      presenting with AML harboring t(8;21)(q22;q22). Her AML was refractory to
      chemotherapy, and bone marrow mastocytosis developed simultaneously at the
      initial diagnosis and during chemotherapy. The D816A mutation of KIT was
      detected. SM associated with t(8;21) AML, accompanied by a KIT mutation in
      children may result in a poor prognosis, despite the fact that t(8;21) AML are
      generally considered to have a favorable risk.

PMID- 22847984
TI  - The embryonic and postembryonic developmental toxicity of imidazolium-based ionic
      liquids on Physa acuta.
AB  - The embryonic and postembryonic developmental toxicity of imidazolium-based ionic
      liquids (ILs) to the snail Physa acuta was evaluated in this study. The results
      of embryonic toxicity tests showed that lower concentrations of 1-octyl-3
      methylimidazolium bromide ([C8 mim]Br) (1.5 and 2.1 mg/L) inhibited the hatching
      rate of snail embryos, and partial snails hatched normally and died, while all of
      the treated embryos died when the exposure concentration was higher than 4.16
      mg/L, at which IL caused the deformation, death, and decay of snail embryos.
      Statistical analyses revealed obvious differences in the hatching rates between
      three developmental stages in the 2.1 and 2.94 mg/L groups, indicating that the
      veliger stage is more sensitive to [C8 mim]Br exposure than the blastula and
      gastrula stages. Furthermore, the 96 h LC50 values of [C8 mim]Br on the tested
      snails at three developmental stages (juvenile, subadult, and adult) were 70.83
      +/- 2.99, 97.59 +/- 4.05, and 109.3 +/- 2.22 mg/L, respectively, indicating that
      young snails were more sensitive to [C8 mim]Br toxicity than adults. In addition,
      the 96 h LC50 values of ILs with different alkyl chain lengths, that is, [C12
      mim], [C10 mim], [C8 mim], and [C6 mim], in adult snails were 1.35 +/- 0.24, 8.96
      +/- 5.66, 109.3 +/- 4, and 359.6 +/- 11.6 mg/L, respectively, suggesting that
      longer alkyl chains can increase the toxicity of imidazolium ILs on snails.

PMID- 22847986
TI  - Evaluation of nanoarchitectured collagen type II molecules on cartilage
      engineering.
AB  - Scaffold architecture, including the geometry and dimension of scaffolds, is an
      important parameter in cell adhesion, migration, proliferation, and
      differentiation. Following the characterization of collagen type II
      nanoarchitectured molecules, collagen fibrils (CNFs) and collagen spheres (CNPs)
      prepared using a high-voltage electric field in our laboratory, we proposed to
      use these nanoarchitectured molecules to assess their influence on the culturing
      of chondrocytes in stirred bioreactors. The results demonstrate that chondrocytes
      rapidly formed more and larger chondrocyte pellets (spheroids) after the addition
      of nanoarchitectured molecules into the culture medium. The maintenance of
      chondrocytes with round morphology and increased glycosaminoglycan secretion
      indicated that these spheroids contained viable and un-dedifferentiated
      chondrocytes. No significant increases in DNA content were detected. These
      results show that the introduction of these molecules did not affect chondrocyte
      proliferation during a 3-day culture period. After the addition of CNPs and CNFs
      into the culture medium, the expression levels of collagen type II and aggrecan
      genes in chondrocytes increased significantly as demonstrated by real-time PCR
      analysis. Interestingly, chondrocytes exhibited distinct collagen type II and
      aggrecan gene expression profiles in culture with CNPs and CNFs. The aggrecan
      gene expression level of the chondrocytes was 2.5-fold greater following CFN
      addition than following the addition of CNPs. In contrast, the collagen type II
      expression level of the chondrocytes was 2.2-fold greater following the addition
      of CNPs than following the addition of CNFs. The chondrocyte pellets rapidly
      restored defects in articular cartilage during a 1-month implantation period in a
      rabbit model.

PMID- 22847985
TI  - Effects of oxygen-glucose deprivation on microglial mobility and viability in
      developing mouse hippocampal tissues.
AB  - As brain-resident immune cells, microglia (MG) survey the brain parenchyma to
      maintain homeostasis during development and following injury. Research in
      perinatal stroke, a leading cause of lifelong disability, has implicated MG as
      targets for therapeutic intervention during stroke. Although MG responses are
      complex, work in developing rodents suggests that MG limit brain damage after
      stroke. However, little is known about how energy-limiting conditions affect MG
      survival and mobility (motility and migration) in developing brain tissues. Here,
      we used confocal time-lapse imaging to monitor MG viability and mobility during
      hypoxia or oxygen-glucose deprivation (OGD) in hippocampal tissue slices derived
      from neonatal GFP-reporter mice (CX3CR1(GFP/+) ). We found that MG remain viable
      for at least 6 h of hypoxia but begin to die after 2 h of OGD, while both hypoxia
      and OGD reduce MG motility. Unexpectedly, some MG retain or recover motility
      during OGD and can engulf dead cells. Additionally, MG from younger neonates (P2
      P3) are more resistant to OGD than those from older ones (P6-P7), indicating
      increasing vulnerability with developmental age. Finally, transient (2 h) OGD
      also increases MG death, and although motility is rapidly restored after
      transient OGD, it remains below control levels for many hours. Together, these
      results show that MG in neonatal mouse brain tissues are vulnerable to both
      transient and sustained OGD, and many MG die within hours after onset of OGD.
      Preventing MG death may, therefore, provide a strategy for promoting tissue
      restoration after stroke.

PMID- 22847987
TI  - Update and external validation of a head and neck cancer prognostic model.
AB  - BACKGROUND: The purpose of this study was to update and external validation of a
      prognostic model that is able to predict the survival probability of newly
      diagnosed patients with head and neck cancer. METHODS: Our original prognostic
      model is based on historical data of 1371 patients with primary head and neck
      cancer, diagnosed and treated in the Leiden University Medical Center, between
      1981 and 1999. The model contains the predictors age, sex, tumor site, TNM
      classification, prior tumors, and comorbidity. We updated the model with follow
      up data until January 2010. The updated model was then externally validated in
      598 patients with head and neck cancer from the Siteman Cancer Center/Barnes
      Jewish Hospital, St. Louis, Missouri. RESULTS: Median follow-up was 5.5 years
      (range, 0-25.5). Only 2.5% of patients were lost to follow-up. During follow-up
      1099 patients (80.2%) passed away. Discrimination of the updated prognostic model
      was good, with a C-index of 0.73 after internal validation. The discrimination
      was slightly lower in the external validation set (C-index, 0.69). The predicted
      2-year and 5-year survival rates correlated satisfactorily with some slight
      deviations from the perfect calibration line. CONCLUSIONS: We used recent follow
      up information to update the Leiden prognostic model for newly diagnosed patients
      with head and neck cancer. The model showed acceptably good calibration and
      discrimination results in internal and external validation procedures.

PMID- 22847988
TI  - Single-walled carbon nanotubes noncovalently functionalized by ruthenium(II)
      complex tagged with pyrene: electrochemical and electrogenerated
      chemiluminescence properties.
AB  - Ru being served: A pyrene-Ru/SWCNT nanohybrid was formed through noncovalent pi
      pi stacking interactions (see figure). After oxidative treatment, the pyrene
      Ru/SWCNT-functionalized Pt electrode achieved a highly reversible redox process
      and exhibited excellent electrogenerated chemiluminescence behavior.

PMID- 22847989
TI  - Tensile testing as a novel method for quantitatively evaluating bioabsorbable
      material degradation.
AB  - Bioabsorbable metallic materials have become a topic of interest in the field of
      interventional cardiology because of their potential application in stents. A
      well-defined, quantitative method for evaluating the degradation rate of
      candidate materials is currently needed in this area. In this study,
      biodegradation of 0.25-mm iron and magnesium wires was simulated in vitro through
      immersion in cell-culture medium with and without a fibrin coating (meant to
      imitate the neointima). The immersed samples were corroded under physiological
      conditions (37 degrees C, 5% CO(2)). Iron degraded in a highly localized manner,
      producing voluminous corrosion product while magnesium degraded more uniformly.
      To estimate the degradation rate in a quantitative manner, both raw and corroded
      samples underwent tensile testing using a protocol similar to that used on
      polymeric nanofibers. The effective ultimate tensile stress (tensile stress
      holding constant cross-sectional area) was determined to be the mechanical metric
      that exhibited the smallest amount of variability. When the effective tensile
      stress data were aggregated, a statistically significant downward, linear trend
      in strength was observed in both materials (Fe and Mg) with and without the
      fibrin coating. It was also demonstrated that tensile testing is able to
      distinguish between the higher degradation rate of the bare wires and the lower
      degradation rate of the fibrin-coated wires with confidence.

PMID- 22847990
TI  - Clinical features and outcomes in patients with secondary Ewing sarcoma.
AB  - BACKGROUND: Ewing sarcoma (EWS) is rarely diagnosed as a second malignancy. We
      sought to describe a cohort of patients with secondary EWS and investigate if
      patient characteristics and survival differ between patients with secondary and
      primary EWS. PROCEDURE: Patients with EWS or peripheral primitive neuroectodermal
      tumor (PNET) reported to the Surveillance, Epidemiology, and End Results Program
      (SEER) database from 1973 to 2008 were evaluated based on primary or secondary
      tumor sequence. Overall survival was estimated by Kaplan-Meier methods and
      evaluated using the log-rank test. Competing risk analysis was used to describe
      risk of death due to malignancy rather than other causes. RESULTS: Fifty-eight
      cases of secondary EWS were reported, accounting for 2.1% of all EWS cases. The
      median latency from primary malignancy to secondary EWS was 64 months (range 1
      282 months). 12.1% of patients with secondary EWS received radiation to the site
      of secondary tumor during therapy for their primary malignancy. Patients with
      secondary EWS were more likely to have axial tumors (77.4% vs. 62.5%; P = 0.03)
      and smaller tumors (75.0% vs. 48.2% <8 cm; P = 0.001). Five-year overall survival
      from diagnosis was inferior for patients with secondary compared to primary EWS
      (34.3% vs. 52.2%; P = 0.002). However, patients with secondary tumors were less
      likely than those with primary EWS to die from their malignancy [hazard ratio
      0.44; 95% confidence interval (CI) 0.23-0.85]. CONCLUSIONS: Secondary EWS
      accounts for a minority of cases of EWS. Tumor size and site and patient survival
      differ among patients with primary and secondary EWS.

PMID- 22847991
TI  - Selective conversion of furfural to maleic anhydride and furan with
      VO(x)/Al(2)O(3) catalysts.
AB  - Furfural can be converted into maleic anhydride (73 % yield) through selective
      gas phase oxidation at 593 K with O(2) by using VO(x)/Al(2)O(3) (10 at(V) nm(-2))
      as solid catalysts. The use of lower temperatures and/or O(2) pressures result in
      the additional formation of furan (maximum 9 % yield). Mechanistically, furfural
      (C(5)H(4)O(2)) is oxidized stepwise to furan (C(4)H(4)O), 2-furanone
      (C(4)H(4)O(2)), and finally, maleic anhydride (C(4)H(2)O(3)). The specific
      structure of the supported vanadium oxides and reaction conditions (temperature
      and reactants pressures) all influence furfural oxidation catalysis. We have
      found that Al(2)O(3)-supported polyvanadates are intrinsically more active (2.70
      mmol h(-1) g-at V(-1)) than monovanadates (VO(4)) and V(2)O(5) crystals (0.89 and
      0.70 mmol h(-1) g-at V(-1), respectively) in maleic anhydride and furan formation
      rates (553 K, 1.6 kPa furfural, 2.5 kPa O(2)). Our alternative approach enables
      the use of biomass instead of petroleum to synthesize maleic anhydride and furan
      from furfural. The potential variety of industrial applications is of enormous
      interest for the development of future biorefineries.

PMID- 22847992
TI  - Acute spill-mimicking exposure effect of hexavalent chromium on the pituitary
      ovarian axis of a teleost, Channa punctatus (Bloch).
AB  - Acute exposure to hexavalent chromium (as 10, 20, and 40 mg/L potassium
      dichromate for 96 h) adversely affected the pituitary-ovarian axis of a teleost
      Channa punctatus. The toxic impact of metal exposure on fish ovary was revealed
      in the form of increased percentage of atretic follicles, significantly in 20
      mg/L and 40 mg/L exposure groups. The follicular atresia mostly occurred in
      vitellogenic (stage II and stage III) oocytes. Reduction of serum level of 17beta
      estradiol was also significant in 20 mg/L and 40 mg/L exposure groups. The
      increase of LH-immunointensity of pituitary gonadotrophs (LHbeta-immunoreactive
      cells) and their hypertrophy was evident, significantly in fish of 40 mg/L
      exposed group. Thus, the present acute metal spill-mimicking laboratory study
      clearly demonstrated that short-term exposures to high doses of hexavalent
      chromium may disrupt reproduction of the fish and affect their population.

PMID- 22847993
TI  - Nonblinking plasmonic quantum dot assemblies for multiplex biological detection.

PMID- 22847994
TI  - Human gingival fibroblasts stress response to HEMA: A role for protein kinase C
      alpha.
AB  - 2-Hydroxyethil methacrylate (HEMA), component of dentin-bonding systems, by
      diffusing into oral cavity induces a cytotoxic response. HEMA determines reactive
      oxygen species (ROS) production activating specific signaling pathways, including
      protein kinases C (PKC). In addition, since a regulation is exerted by various
      PKCs on nitric oxide synthase (NOS) activation, our aim was to investigate the
      role of PKCs and the possible interplay with ROS and NO signaling system in human
      gingival fibroblasts (HGF) response to HEMA. Cultured HGFs were exposed to 3 mM
      (a subtoxic concentration) HEMA for 0, 24, or 96 h. Each experimental point were
      processed for flow cytometry, fluorescence microscopy, western blotting, and "in
      vitro" NOS specific activity analyses. Three millimolar HEMA reduces HGF
      proliferation less than 50% and increases apoptosis percentage up to 18%. Both
      ROS production and PKC alpha expression and activation are also increased 96 h
      after HEMA exposure. The increased specific activity of iNOS, inflammatory
      enzyme, accompanied by Bax high expression in HGF response to 96 h HEMA, document
      the occurrence of an inflammatory and apoptotic response to such agent.
      Interestingly, a reduced percentage of apoptotic cells and a reduced ROS
      production are evidenced in the presence of bisindolylmaleide VIII, a PKC alpha
      pharmacologic inhibitor. All in all, these results suggest that PKC alpha can
      mediate the inflammatory response disclosed by gingival fibroblasts to HEMA
      released monomers.

PMID- 22847995
TI  - Pilot, randomized trial of resistance exercise during radiation therapy for head
      and neck cancer.
AB  - BACKGROUND: The purpose of this study was to determine the feasibility of a
      randomized trial of resistance exercise in patients with head and neck cancer
      receiving radiation. METHODS: Fifteen patients with head and neck cancer
      receiving radiation were randomized to resistance exercise (using resistance
      bands) or control group. Resistance exercise occurred at the radiation therapy
      site (weeks 1-6) and home (weeks 7-12). RESULTS: No serious adverse events
      occurred related to resistance exercise. Medium to large effect size differences
      favoring resistance exercise versus control group were noted for perceived
      fatigue at 6 weeks (smaller increase in fatigue for resistance exercise group;
      7.4 vs 15.4, effect size [d] = -0.64), quality of life at 6 weeks (-7.0 vs -14.4,
      d = 0.52), and chair rise time (seconds) at 6 and 12 weeks (-1.6 vs 0.4, d = -.63
      and -1.9 vs 0.1, d = -0.60, respectively). CONCLUSIONS: Resistance exercise is
      safe and feasible in patients with head and neck cancer receiving radiation; a
      definitive trial is warranted.

PMID- 22847997
TI  - Ring-opening polymerization of genipin and its long-range crosslinking effect on
      collagen hydrogel.
AB  - Polymeric genipin macromers, prepared by ring-opening polymerization at various
      pH values, are used as crosslinking agents to fix collagen hydrogels. The results
      indicate that as the dark color of polymeric genipin itself and the networks
      formed by long-range intermolecular crosslinking, the genipin-fixed collagen
      hydrogels displace darker color. The polymeric genipin prepared at higher pH
      value needs longer time to fully crosslink with collagen molecules. Moreover,
      polymerization of genipin reduces the yield of genipin-fixed collagen hydrogels
      due to low extent of crosslinking. Specially, the microscope photographs present
      the porous networks structures of genipin-fixed collagen hydrogels. The pore size
      increases with the increase in polymerization degree of genipin. The data of FTIR
      indicate the likely transition of -NH(2) groups in collagen chains into C=N.
      Owning to much more number of hydrophilic groups and more porous networks,
      collagen hydrogels fixed by genipin with higher polymerization degree have higher
      water absorption capacity. The equilibrium swelling of genipin-fixed collagen
      hydrogels is pH-responsive, which show "M" type changes with the pH values. The
      results obtained in the study suggest that the polymeric genipin prepared at
      various pH values lead to significant influence to the crosslinking
      characteristics and properties of collagen hydrogels.

PMID- 22847998
TI  - Characterization and preosteoblastic behavior of hydroxyapatite-deposited
      nanotube surface of titanium prepared by anodization coupled with alternative
      immersion method.
AB  - The modification on the titanium (Ti) implant surface is an effective method to
      improve the bioactivity of Ti. In this study, a hydroxyapatite (HA)-deposited
      nanotubular Ti surface was prepared by anodization coupled with an alternative
      immersion method (AIM). Surface physicochemical characteristics including
      morphology, microstructure, composition, roughness were evaluated by field
      emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier
      transformed infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS)
      and atomic force microscopy (AFM). Preosteoblast cell (MC3T3-E1) behavior on the
      HA-deposited nanotube surface, including cell morphology, proliferation, alkaline
      phosphatase (ALP) activity, osteocalcin secretion, and mineralization, were also
      investigated. The untreated nanotube surface and bare Ti were used as controls.
      The results showed that synthetic HA crystals could be efficiently grown
      on/inside the nanotubes after AIM treatment in saturated Ca(OH)(2) and 0.02M
      (NH(4))(2) HPO(4). The amount of synthetic HA on nanotube layer was dependent on
      the number of dipping cycles. Significant increases in ALP activity and
      osteocalcin production on day 7 and 14 and calcium deposition on day 21 (P <
      0.05) were observed for HA-deposited nanotubular Ti surface when compared with
      untreated nanotube layer and bare Ti. However, the cell proliferation rate on HA
      deposited nanotube surfaces was slowed down significantly (P < 0.05). All these
      results indicated that this HA-deposited nanotube surface might have the
      potential benefit to enhance implant osseointegration. The synthetic HA TiO(2)
      nanotube loading might be a highly promising path to improve the bioactivity of
      Ti-based implants.

PMID- 22847996
TI  - KSRP: a checkpoint for inflammatory cytokine production in astrocytes.
AB  - Chronic inflammation in the central nervous system (CNS) is a central feature of
      many neurodegenerative and autoimmune diseases. As an immunologically competent
      cell, the astrocyte plays an important role in CNS inflammation. It is capable of
      expressing a number of cytokines such as tumor necrosis factor alpha (TNF-alpha)
      and interleukin-1 beta (IL-1beta) that promote inflammation directly and through
      the recruitment of immune cells. Checkpoints are therefore in place to keep tight
      control over cytokine production. Adenylate/uridylate-rich elements (ARE) in the
      3' untranslated region of cytokine mRNAs serve as a major checkpoint by
      regulating mRNA stability and translational efficiency. Here, we examined the
      impact of KH-type splicing regulatory protein (KSRP), an RNA binding protein
      which destabilizes mRNAs via the ARE, on cytokine expression and paracrine
      phenotypes of primary astrocytes. We identified a network of inflammatory
      mediators, including TNF-alpha and IL-1beta, whose expression increased 2 to 4
      fold at the RNA level in astrocytes isolated from KSRP(-/-) mice compared to
      littermate controls. Upon activation, KSRP(-/-) astrocytes produced TNF-alpha and
      IL-1beta at levels that exceeded control cells by 15-fold or more. Conditioned
      media from KSRP(-/-) astrocytes induced chemotaxis and neuronal cell death in
      vitro. Surprisingly, we observed a prolongation of half-life in only a subset of
      mRNA targets and only after selective astrocyte activation. Luciferase reporter
      studies indicated that KSRP regulates cytokine gene expression at both
      transcriptional and post-transcriptional levels. Our results outline a critical
      role for KSRP in regulating pro-inflammatory mediators and have implications for
      a wide range of CNS inflammatory and autoimmune diseases.

PMID- 22847999
TI  - Synthesis, coupling, and condensation reactions of 1,2-diborylated benzenes: an
      experimental and quantum-chemical study.
AB  - 1,2-Bis(pinacolboryl)benzene (1,2-C(6)H(4) (Bpin)(2), 2) was synthesized in
      preparatively useful yields from 1,2-C(6)H(4)Br(2), iPrO-Bpin, and Mg turnings in
      the presence of 1,2-C(2)H(4)Br(2) as an entrainer. Compound 2 is a versatile
      starting material for the synthesis of (un)symmetrically substituted benzenes
      (i.e., 1,2-C(6)H(4)(Ar(1))(Ar(2))) through sequential Suzuki-Miyaura coupling
      reactions. Alternatively, it can be transformed into bis-borate Li(2)[1,2
      C(6)H(4)(BH(3))(2)] (3) through reduction with Li[AlH(4)]. In the crystal
      lattice, the diethyl ether solvate 3.OEt(2) establishes a columnar structure that
      is reinforced by an intricate network of B-(MU-H)-Li interactions. Hydride
      abstraction from compound 3 with Me(3)SiCl leads to the transient ditopic borane
      1,2-C(6)H(4)(BH(2))(2), which can either be used in situ for subsequent
      hydroboration reactions or trapped as its stable NMe(2)Et diadduct (6). In SMe(2)
      solution, the putative diadduct 1,2-C(6)H(4)(BH(2).SMe(2))(2) is not long-term
      stable but rather undergoes a condensation reaction to give 9,10-dihydro-9,10
      diboraanthracene, HB(MU-C(6)H(4))(2)BH, and BH(3). 9,10-Dihydro-9,10
      diboraanthracene was isolated from the reaction mixture as its SMe(2) monoadduct
      (7), which dimerizes in the solid state through two B-H-B bridges ((7)(2),
      elucidated by X-ray crystallography). In contrast, hydride-abstraction from
      compound 3 in THF or CH(2)Cl(2) provides the unique exo-adduct H(2)B(MU-H)(2)B(MU
      C(6)H(4))(2)B(MU-H)(2)BH(2) (8, elucidated by X-ray crystallography). Quantum
      chemical calculations on various conceivable isomers of [1,2
      C(6)H(4)(BH(2))(2)](2) revealed that compound 8 was the most stable of these
      species. Moreover, the calculations confirmed the experimental findings that the
      NMe(2)Et diadduct of 1,2-C(6)H(4)(BH(2))(2) is significantly more stable than the
      corresponding SMe(2) complex and that the latter complex is not able to compete
      successfully with borane-dimerization and -condensation. The reaction cascade in
      SMe(2), which proceeds from 1,2-C(6)H(4)(BH(2))(2) to the observed adducts of
      HB(MU-C(6)H(4))(2)BH, has been elucidated in detail and the important role of B-C
      B-bridged intermediates has been firmly established.

PMID- 22848000
TI  - Late effects of total body irradiation and hematopoietic stem cell transplant in
      children under 3 years of age.
AB  - BACKGROUND: Total body irradiation (TBI) is an important component of
      hematopoietic stem cell transplant (SCT) for pediatric malignancies. With
      increasing survival rates, late effects of SCT become more important. Younger
      children may be at particular risk of late effects of radiation and SCT. METHODS:
      We retrospectively reviewed outcomes of children less than 3 years of age who
      received TBI as part of their preparative regimen for SCT at Children's Hospital
      Colorado. Clinical information including the date of last follow-up, most recent
      lab values, and physiologic tests were extracted from the medical record.
      RESULTS: Of 81 patients who underwent SCT, 19 received TBI and of those, 15 were
      long-term survivors available for review. Late effects occurring in greater than
      50% of the children included abnormalities involving endocrine, metabolic, renal,
      cataracts, and neurocognitive systems. Other organs involved less commonly
      included liver, skeletal, and cardiac abnormalities. Solid tumors were a rare
      finding with only one patient developing a benign osteochondroma and no
      identified secondary malignancies. CONCLUSIONS: TBI has been shown to be an
      important part of the preparative regimen for patients undergoing SCT. Our
      results, similar to other studies, suggest TBI in patients less than 3 years of
      age will likely result in multi-organ dysfunction including endocrine, metabolic,
      renal, eye, and neurocognitive abnormalities. A longitudinal study with
      standardized testing of these systems would further clarify the late effects
      concerns in this patient population.

PMID- 22848001
TI  - Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is
      mediated through increasing reactive oxygen species and decreasing the level of
      mitochondrial membrane potential.
AB  - Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone
      compounds, and it has been shown to induce cell death in different types of
      cancer cells. The effects of chrysophanol on human lung cancer cell death have
      not been well studied. The purpose of this study is to examine chrysophanol
      induced cytotoxic effects and also to investigate such influences that involved
      apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results
      indicated that chrysophanol decreased the viable A549 cells in a dose- and time
      dependent manner. Chrysophanol also promoted the release of reactive oxygen
      species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane
      potential (DeltaPsim ) and adenosine triphosphate in A549 cells. Furthermore,
      chrysophanol triggered DNA damage by using Comet assay and DAPI staining.
      Importantly, chrysophanol only stimulated the cytocheome c release, but it did
      not activate other apoptosis-associated protein levels including caspase-3,
      caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated
      with chrysophanol exhibited a cellular pattern associated with necrotic cell
      death and not apoptosis in vitro. (c) 2012 Wiley Periodicals, Inc. Environ
      Toxicol 29: 740-749, 2014. 

PMID- 22848002
TI  - Direct visualization of the movement of a single T7 RNA polymerase and
      transcription on a DNA nanostructure.

PMID- 22848003
TI  - Efficient water splitting via a heteroepitaxial BiVO(4) photoelectrode decorated
      with Co-Pi catalysts.

PMID- 22848004
TI  - Surgical management of bilateral parotid lipomatosis in a patient with HIV.
AB  - BACKGROUND: The long-term use of highly active antiretroviral therapy (HAART) in
      patients with human immunodeficiency virus (HIV) has led to sequelae including
      lipodystrophy syndrome (LDS). We present the first published case of surgical
      management of bilateral parotid lipomatosis in a patient with HIV on long-term
      HAART. METHODS: We undertook review of the case notes from the time of diagnosis
      with HIV and literature review of this topic. RESULTS: A 45-year-old man with HIV
      on HAART presented with a 4-year history of increasing bilateral facial swelling.
      He was asymptomatic apart from the stigmatizing cosmetic deformity. MRI revealed
      the parotid glands had been replaced by fat. He elected for surgery and parotid
      lipomatosis was diagnosed on histopathological examination. CONCLUSION:
      Lipohypertrophy in LDS is rare in the literature and this presentation of
      bilateral parotid lipomatosis secondary to HAART is only the third reported case,
      and the first to undergo surgical resection.

PMID- 22848005
TI  - Spinal duraplasty with two novel substitutes restored locomotor function after
      acute laceration spinal cord injury in rats.
AB  - A dural tear is a common complication after acute laceration spinal cord injury
      (ALSCI). An unrepaired dural tear is associated with poor locomotor functional
      recovery. Spinal duraplasty with biomaterials may promote functional recovery in
      ALSCI. However, an ideal dural substitute has not yet been found. In this work,
      we investigated the possibility of using a denuded human amniotic membrane (DHAM)
      or DHAM seeded on bone marrow stromal cells (DHAM-BMSCs) as duraplasty
      biomaterials. We patched broken dura with the two novel substitutes in an ALSCI
      rat model. At the end of the eighth week, we observed that the neural motor
      function was recovered according to the Basso-Beattie-Bresnahan scale, and the
      neural loop was successfully reestablished between the ends of the lesions by
      motor-evoked potentials in the duraplasty groups. Moreover, the DHAM-BMSCs
      repaired the dura and resulted in a significant reduction in the total lesion and
      cystic volumes by nearly 10-fold versus the control group (p < 0.01). The levels
      of neurotrophic factors and NF-200-positive fibers were also improved in the
      duraplasty groups, compared to the control group. Our data suggest that the two
      novel substitutes may be promising grafts for patching dural defects to improve
      locomotor function after ALSCI.

PMID- 22848006
TI  - Body compositional and cardiometabolic effects of testosterone therapy in obese
      men with severe obstructive sleep apnoea: a randomised placebo-controlled trial.
AB  - BACKGROUND: The combination of male gender, obstructive sleep apnoea (OSA) and
      obesity magnifies cardiometabolic risk. There has been no systematic study
      evaluating whether testosterone therapy can improve cardiometabolic health in
      obese men with OSA by improving body composition, visceral abdominal fat and
      insulin sensitivity. OBJECTIVE: To assess body compositional and cardiometabolic
      effects of testosterone treatment in obese men with severe OSA. DESIGN: An 18
      week randomised, double-blind, placebo-controlled and parallel group trial in 67
      men. METHODS: Participants (age=49 +/- 12 years, apnoea hypopnoea index=39.9 +/-
      17.7 events/h, BMI=31.3 +/- 5.2 kg/m(2)) were placed on a hypocaloric diet and
      received i.m. injections of either 1000 mg testosterone undecanoate (n=33) or
      placebo (n=34) for 18 weeks. Outcomes were the changes in body composition (total
      muscle mass, total and abdominal fat, total body dual-energy X-ray absorptiometry
      and computerised tomography (CT)), weight, insulin sensitivity (homeostasis model
      assessment), abdominal liver fat (CT), arterial stiffness (pulse wave analysis),
      resting metabolic rate and respiratory quotient (indirect calorimetry) and blood
      lipids and metabolic syndrome from baseline to week 18. RESULTS: After 18 weeks,
      testosterone treatment increased insulin sensitivity (-1.14 units, 95% confidence
      interval (95% CI) -2.27 to -0.01, P<0.05), reduced liver fat (0.09 Hounsfield
      attenuation ratio, 95% CI 0.009 to 0.17, P=0.03) and increased muscle mass (1.6
      kg, 95% CI 0.69 to 2.5, P=0.0009) to a greater extent than placebo. Other
      measures of body composition and regional adiposity as well as the number of
      participants with metabolic syndrome did not change. Testosterone also decreased
      arterial stiffness (augmentation index) by 3.2% (95% CI -6.01 to -0.46%, P=0.02)
      and decreased the respiratory quotient (95% CI -0.04, -0.08 to -0.001, P=0.04)
      after 18 weeks compared with placebo. CONCLUSION: Eighteen weeks of testosterone
      therapy in obese men with OSA improved several important cardiometabolic
      parameters but did not differentially reduce overall weight or the metabolic
      syndrome. Longer term studies are required.

PMID- 22848007
TI  - Sex-related differences of cAMP-specific PDE4B3 mRNA in oligodendrocytes
      following systemic inflammation.
AB  - Sex-related differences have been observed in the incidence and severity of
      several neurological diseases and in sepsis in humans. Cyclic adenosine
      monophosphate (cAMP) has been shown to play an important role in modulating the
      inflammatory environment during neuroinflammation and importantly in protecting
      myelin from excitotoxic cell death. Considering the sexual dimorphism in the
      functional properties of oligodendrocytes and the importance of a systemic
      inflammation in the progression of multiple sclerosis, we focused on identifying
      possible sex-related differences in the alterations previously reported for the
      two phosphodiesterase4B (PDE4B) splice-variants (PDE4B2 and PDE4B3) mRNA
      expression during innate neuroinflammation. PDE4A, PDE4B, and PDE4D are present
      in oligodendrocytes and we have previously reported that PDE4B3 mRNA is readily
      expressed in both oligodendrocytes and neurons. In this study, we analyzed the
      influence of an intraperitoneal lipopolysaccharide injection on the distribution
      pattern and expression levels of the PDE4B mRNA splicing variants in both male
      and female mice brains. Clear differences were observed in PDE4B2 and PDE4B3 mRNA
      expression levels in males compared with females in a time-dependent manner.
      Furthermore, we observed that the clear downregulation of PDE4B3 mRNA was
      reflected in a lower percentage of oligodendrocytes positive for this transcript
      which correlated with a decrease in inducible cAMP early repressor expression in
      female corpus callosum.

PMID- 22848008
TI  - Medium chain acyl-CoA dehydrogenase deficiency detected among Hispanics by New
      Jersey newborn screening.
AB  - In the follow-up of New Jersey newborn screens suggestive of medium chain acyl
      CoA dehydrogenase deficiency (MCADD) during a 30-month period, we identified five
      patients of Hispanic American ethnicity. With information provided by the New
      Jersey Department of Health and Human Services Newborn Screening program we
      calculated an overall cumulative incidence of approximately 7.20/100,000 for
      MCADD; 7.58/100,000 among Hispanic Americans and 7.08/100,000 among non-Hispanic
      Americans. Among the five Hispanic American infants who screened positive, a
      common variant (c.443G>A [p.R148K]) was identified which accounted for 30% of the
      alleles; c.799G>A (p.G267R) and c.985A>G (p.K329E) each accounted for an
      additional 20%; and a novel variant c.302G>A (p.G101E) was identified in one
      patient. Although treated prospectively during interim illnesses to prevent
      unwanted sequelae; till date, none of the patients carrying the c.443G>A variant
      have been symptomatic.

PMID- 22848009
TI  - Self-assembly of folic acid: a chiral-aligning medium for enantiodiscrimination
      of organic molecules in an aqueous environment.
AB  - Weak orienting medium: Self-assembly of alkaline salt of folic acid yielded a
      weak liquid-crystalline phase in an aqueous environment. This medium has the
      ability to discriminate enantiomers. The mesophase exists over a broad range and
      has the physical parameter dependent tunability of degree of alignment (see
      scheme).

PMID- 22848010
TI  - Signatures of the Rayleigh-plateau instability revealed by imposing synthetic
      perturbations on nanometer-sized liquid metals on substrates.

PMID- 22848011
TI  - A systematic review of models of care for the follow-up of childhood cancer
      survivors.
AB  - Follow-up care for survivors of childhood cancer is increasingly seen as a
      priority service as numbers of survivors increase. Despite this there are few
      published evaluations of the available options. We conducted a systematic review
      of published and unpublished literature. Seven uncontrolled studies, and one
      comparative study of a related intervention, were identified. Observational data
      suggest that follow-up care was useful even for patients who did not perceive
      this as a need. Suitably powered, well-conducted, controlled trials of adequate
      duration that directly compare follow-up models are required to provide robust
      evidence on the optimal care for these patients.

PMID- 22848012
TI  - Oxidative methane upgrading.
AB  - The economically viable oxidative upgrading of methane presents one of the most
      difficult but rewarding challenges within catalysis research. Its potential to
      revolutionalise the chemical value chain, coupled with the associated supremely
      challenging scientific aspects, has ensured this topic's high popularity over the
      preceeding decades. Herein, we report a non-exhaustive account of the current
      developments within the field of oxidative methane upgrading and summarise the
      pertaining challenges that have yet to be solved.

PMID- 22848013
TI  - Concordance between physiological arousal and subjective distress among Vietnam
      combat veterans undergoing challenge testing for PTSD.
AB  - This study examined concordance between physiological arousal and subjective
      distress during a laboratory challenge task. Data were collected during the
      multisite VA Cooperative Study 334 in the early 1990s examining
      psychophysiological arousal among combat-exposed Vietnam veterans with (n = 775)
      and without (n = 369) posttraumatic stress disorder (PTSD). Study participants
      were presented with 6 standardized neutral scenes and 6 standardized combat
      scenes. Participants provided a subjective rating of distress after each slide.
      During the presentation, levels of heart rate (HR) and skin conductance (SC) were
      recorded. Using linear mixed effects modeling, both HR level and SC level
      exhibited significant positive associations with subjective distress ratings (pr
      = .33, p < .001 and pr = .19, p < .001, respectively). Individuals with PTSD
      demonstrated greater concordance between their distress ratings and SC level
      during exposure to combat slides than participants without PTSD (pr = .28, p <
      .001 vs. pr = .18, p < .001). Although a significant association was found
      between subjective distress and HR reactivity and SC reactivity, these findings
      were not moderated by PTSD status. The results of these analyses suggest that
      patients' reports of distress during exposure-based treatments might serve as
      approximate measures of actual physiological arousal.

PMID- 22848014
TI  - Methylenetetrahydrofolate reductase (MTHFR) deficiency presenting as a rash.
AB  - We report on the case of a 2-year-old girl recently diagnosed with
      Methylenetetrahydrofolate reductase (MTHFR) deficiency who originally presented
      in the neonatal period with a distinctive rash. At 11 weeks of age she developed
      seizures, she had acquired microcephaly and developmental delay. The rash
      deteriorated dramatically following commencement of phenobarbitone; both rash and
      seizures abated following empiric introduction of pyridoxine and folinic acid as
      treatment of possible vitamin responsive seizures. We postulate that
      phenobarbitone in combination with MTHFR deficiency may have caused her rash to
      deteriorate and subsequent folinic acid was helpful in treating the rash and
      preventing further acute neurological decline as commonly associated with this
      condition.

PMID- 22848015
TI  - High-nuclearity silver ethynide clusters assembled with phosphonate and
      metavanadate precursors.

PMID- 22848017
TI  - Optic pathway glioma as part of a constitutional mismatch-repair deficiency
      syndrome in a patient meeting the criteria for neurofibromatosis type 1.
AB  - Patients with constitutional mismatch repair-deficiency (CMMR-D) caused by the
      biallelic deletions of mismatch repair (MMR) genes have a high likelihood of
      developing malignancies of the bone marrow, bowel, and brain. Affected
      individuals often have phenotypic features of neurofibromatosis type 1 (NF-1),
      including cafe-au-lait spots. Optic pathway gliomas (OPGs), a common
      manifestation of NF-1, have not been reported. We report the case of a 3-year-old
      male with an extensive OPG who met the diagnostic criteria for NF-1. He was
      subsequently found to have multiple colonic polyps and bi-allelic loss of PMS2.
      Testing for NF-1 was negative.

PMID- 22848016
TI  - Real-time monitoring of influenza virus production kinetics in HEK293 cell
      cultures.
AB  - There is an increased interest from the vaccine industry to use mammalian cell
      cultures for influenza vaccine manufacturing. Therefore, it became important to
      study the influenza infection mechanism, the viral-host interaction, and the
      replication kinetics from a bioprocessing stand point to maximize the influenza
      viral production yield in cell culture. In the present work, influenza
      replication kinetics was studied in HEK293 cells. Two infection conditions were
      evaluated, a low (0.01) and a high multiplicity of infection (1.0). Critical time
      points of the viral production cycle (infection, protein synthesis, viral
      assembly and budding, viral release, and host-cell death) were identified in
      small-scale cell cultures. Additionally, cell growth, viability, and viral titers
      were monitored in the viral production process. The infection state of the
      cultivated cell population was assessed by influenza immunolabeling throughout
      the culture period. Influenza virus production kinetics were also on-line
      monitored by dielectric spectroscopy and successfully correlated to real-time
      capacitance measures. Overall, this work provided insights into the mechanisms
      associated with the infection of human HEK293 cell line by the influenza virus
      and demonstrated, once again, the usefulness of multifrequency scanning
      permittivity for in-line monitoring and supervision of cell-based viral
      production processes.

PMID- 22848018
TI  - Total synthesis of (-)-lemonomycin.

PMID- 22848019
TI  - Gd-EOB-DTPA-enhanced MR imaging: prediction of hepatic fibrosis stages using
      liver contrast enhancement index and liver-to-spleen volumetric ratio.
AB  - PURPOSE: To develop and evaluate a quantitative parameter for staging hepatic
      fibrosis by contrast enhancement signal intensity and morphological measurements
      from gadoxetic acid (Gd-EOB-DTPA)-enhanced MR imaging. MATERIALS AND METHODS: MR
      images were obtained in 93 patients; 75 patients had histopathologically proven
      hepatic fibrosis and 18 patients who had healthy livers were evaluated. The liver
      to-muscle signal intensity ratio (SI(post) = SIliver/SImuscle), contrast
      enhancement index (CEI = SIpost/SIpre), and liver-to-spleen volumetric ratio (VR
      = Vliver/Vspleen) were evaluated for staging hepatic fibrosis. RESULTS: VR was
      most strongly correlated with fibrosis stage (7.21; r = -0.83; P < 0.001).
      Sensitivity, specificity, and area under the ROC curve demonstrated by linear
      regression formula generated by VR and CEI in predicting fibrous scores were
      100%, 73%, and 0.91, respectively, for the detection of hepatic fibrosis F1 or
      greater (>= F1),100%, 87%, and 0.96 for >= F2, 74%, 98%, and 0.93 for >= F3 and
      91%, 100%, and 0.97 for F4. CONCLUSION: The liver-to-spleen volumetric ratio and
      contrast enhancement index were reliable biomarkers for the staging of hepatic
      fibrosis on Gd-EOB-DTPA-enhanced MR imaging.

PMID- 22848020
TI  - Behavioural changes add validity to the construct of posttraumatic growth.
AB  - This study aimed to identify positive behavioural changes that people may make as
      a result of negotiating the aftermath of a traumatic experience, thereby
      extending the current cognitive model of posttraumatic growth (PTG). It was
      hypothesised that significant others would corroborate survivors' cognitive and
      behavioural reports of PTG. The sample comprised 176 participants: 88 trauma
      survivors and 88 significant others. University students accounted for 64%; 36%
      were from the broader community. Approximately one third were men. All
      participants completed the Posttraumatic Growth Inventory (PTGI) and open-ended
      questions regarding behavioural changes. The PTGI scores of the survivors were
      corroborated by their significant others with only the Appreciation of Life
      factor of the PTGI differing between the 2 groups (e.g., total PTGI scores
      between groups explained 33% of variance). Nearly all of the survivors also
      reported positive changes in their behaviour; these changes were also
      corroborated by the significant others. Results provide validation of the PTG
      construct and the PTGI as an instrument of measurement. Findings may also
      influence therapeutic practice by pointing to the potential usefulness of
      corroborating others in the recovery and growth process.

PMID- 22848021
TI  - Global longitudinal strain predicts left ventricular dysfunction after mitral
      valve repair.
AB  - AIMS: Despite a successful surgical procedure and adherence to current
      recommendations, postoperative left ventricular (LV) dysfunction after mitral
      valve repair (MVr) for organic mitral regurgitation (MR) may still occur. New
      approaches are therefore needed to detect subclinical preoperative LV
      dysfunction. LV global longitudinal strain (GLS), assessed with speckle-tracking
      echocardiographic analysis, has been proposed as a novel measure to better depict
      latent LV dysfunction. The aim of this study was to investigate the value of GLS
      to predict long-term LV dysfunction after MVr. METHODS AND RESULTS: A total of
      233 patients (61% men, 61 +/- 12 years) with moderate-severe organic MR who
      underwent successful MVr between 2000 and 2009 were included. Echocardiography
      was performed at baseline and long-term follow-up (34 +/- 20 months) after MVr.
      LV dysfunction at follow-up was defined as LV ejection fraction (EF) <50% and was
      present in 29 (12%) patients. A cut-off value of -19.9% of GLS showed a
      sensitivity and specificity of 90 and 79% to predict long-term LV dysfunction. By
      univariate logistic regression analysis, baseline LVEF <=60%, LV end-systolic
      diameter (ESD) >=40 mm, atrial fibrillation, presence of symptoms, and GLS >
      19.9% were predictors of long-term LV dysfunction. By multivariate analysis, GLS
      remained an independent predictor of LV dysfunction (odds ratio 23.16, 95%
      confidence interval: 6.53-82.10, P < 0.001), together with LVESD. CONCLUSION: In
      a large series of patients operated within the last decade, MVr resulted in a low
      incidence of long-term LV dysfunction. A GLS of >-19.9% demonstrated to be a
      major independent predictor of long-term LV dysfunction after adjustment for
      parameters currently implemented into guidelines.

PMID- 22848022
TI  - Left ventricular cleft.

PMID- 22848023
TI  - De novo microdeletion of 5q14.3 excluding MEF2C in a patient with infantile
      spasms, microcephaly, and agenesis of the corpus callosum.
AB  - The 5q14.3 microdeletion syndrome has recently been recognized as a clinical
      entity manifesting as severe intellectual disability, epilepsy, and brain
      malformations. Analysis of the shortest region of overlap among patients with
      this syndrome and subsequent identification of nucleotide alterations in the
      coding region of myocyte enhancer factor 2C gene (MEF2C) have suggested MEF2C as
      the gene responsible for the 5q14.3 microdeletion syndrome. We identified a de
      novo 3.4-Mb deletion of 5q14.3 in a patient with infantile spasms, microcephaly,
      and brain malformation. The deleted region in the present patient was positional
      toward the centromere, and MEF2C was not included in the deleted region. However
      the neurological and dysmorphic features of the present patient resembled those
      of patients with the 5q14.3 microdeletion syndrome. We consider that a positional
      effect is the likely explanation for this evidence. To study the precise
      mechanism of this positional effect, further information is required on patients
      showing atypical deletions neighboring MEF2C.

PMID- 22848024
TI  - Iron-catalyzed alkyl-alkyl Suzuki-Miyaura coupling.

PMID- 22848026
TI  - Beneficial effect of protracted sterilization of lentils on phytase production by
      Aspergillus ficuum in solid state fermentation.
AB  - Water addition to the solid substrate preceding autoclaving increased substrate
      porosity and phytase production in solid state fermentation. In comparison with
      dry sterilization, the phytase activity increased 6-, 8.5-, and 10-fold when the
      autoclaving time was 20, 40, and 60 min, respectively. Autoclaving increased the
      void space of sterilized lentils, and the increase was 16% higher when water was
      supplemented to the lentils before sterilization. Image analysis of SEM pictures
      of the solid substrate showed that water supplementation presterilization
      portended greater micro-fissure surface area, which also increased with
      increasing the sterilization time. SEM pictures of the fermentation product
      showed that fungal growth into the center of the solid substrate was ubiquitous
      when water was supplemented before sterilization but was absent when water was
      supplemented post sterilization. Similarly, spore formation on the substrate
      surface for the presterilization water supplementation samples far exceeded spore
      formation for samples that received supplementation poststerilization. This
      evidence suggests that improved mass transfer into the solid substrate resulting
      from additional pore volume and the formation of micro-fissures on the substrate
      surface is responsible for the observed gains in phytase productivity in solid
      state fermentation.

PMID- 22848025
TI  - Psychoactive medication use and neurocognitive function in adult survivors of
      childhood cancer: a report from the Childhood Cancer Survivor study.
AB  - BACKGROUND: Adult survivors of childhood cancer are at risk for long-term
      morbidities, which may be managed pharmacologically. Psychoactive medication
      treatment has been associated with adverse effects on specific neurocognitive
      processes in non-cancer populations, yet these associations have not been
      examined in adult survivors of childhood cancer. PROCEDURE: Outcomes were
      evaluated in 7,080 adult survivors from the Childhood Cancer Survivor Study
      (CCSS) using a validated self-report Neurocognitive Questionnaire. Multivariable
      logistic regression models were used to calculate odds ratios (OR) and 95%
      confidence intervals (CI) for neurocognitive impairment using demographic and
      treatment factors and survivors' report of prescription medication use. RESULTS:
      Controlling for cranial radiation, pain, psychological distress, and
      stroke/seizure, use of antidepressant medications was associated with impaired
      task efficiency (OR = 1.80, 95% CI = 1.47-2.21), organization (OR = 1.83, 95% CI
      = 1.48-2.25), memory (OR = 1.53, 95% CI = 1.27-1.84), and emotional regulation
      (OR = 2.06, 95% CI = 1.70-2.51). Neuroleptics and stimulants were associated with
      impaired task efficiency (OR = 2.46, 95% CI = 1.29-4.69; OR = 2.82, 95% CI = 1.61
      4.93, respectively) and memory (OR = 2.08, 95% CI = 1.13-3.82; OR = 2.69, 95% CI
      = 1.59-4.54, respectively). Anticonvulsants were associated with impaired task
      efficiency, memory, and emotional regulation, although survivors who use these
      medications may be at risk for neurocognitive impairment on the basis of seizure
      disorder and/or underlying tumor location (CNS). CONCLUSIONS: These findings
      suggest that specific psychoactive medications and/or mental health conditions
      may be associated with neurocognitive function in adult survivors of childhood
      cancer. The extent to which these associations are causal or indicative of
      underlying neurological impairment for which the medications are prescribed
      remains to be ascertained.

PMID- 22848027
TI  - Carcass weight, condition and reproduction of wild boar harvested in north
      western Poland.
AB  - BACKGROUND: Wild boar were studied in the Gryfino-Mysliborz region of Poland
      where high-density populations inflict great damage to farmlands. The
      reproductive tracts from carcasses bagged during the 2008/2009 hunting season
      were analysed for numbers of corpora lutea and embryos. The objective was to
      determine the reproduction rate in a wild boar population having access to high
      protein food in cereal monocultures. RESULTS: Among the wild boar harvested (n =
      165), 35.8% were piglets, 53.9% were yearlings and 10.3% were older boar. Among
      the 105 females examined, 60.9% did not reproduce. The presence of corpora lutea
      was found in 22.9% of females, whereas 16.2% of females had embryos. In piglets,
      11.5% of females had corpora lutea and embryos. These proportions were higher in
      yearlings (41.1%) and in older females (45.4%). The average number was 6.3 of
      corpora lutea per ovulating female, with an average litter size of 5.9 embryos.
      The farrowing period was found to last from December to August. CONCLUSIONS: The
      proportion of piglets in the harvest quota must be increased to prevent these
      animals from boosting reproduction. Offering high-protein fodder in baiting
      stations and feeding sites should be banned.

PMID- 22848028
TI  - Lupenone isolated from Adenophora triphylla var. japonica extract inhibits
      adipogenic differentiation through the downregulation of PPARgamma in 3T3-L1
      cells.
AB  - Adenophora triphylla var. japonica (Campanulaceae) is known to have anti
      inflammatory and anti-tussive effects. Dysfunction of adipocytes and adipose
      tissue in obesity is related to various inflammatory cytokines or adipokines. In
      this study, we investigated whether lupenone isolated from A. triphylla var.
      japonica extract inhibits adipocyte differentiation and expression of adipogenic
      marker genes in 3T3-L1 preadipocytes. We demonstrated that lupenone resulted in a
      significant reduction in lipid accumulation and expression of adipogenic marker
      genes in a dose-dependent manner. In addition, lupenone decreased the
      transcriptional activity of peroxisome proliferator-activated receptor gamma
      (PPARgamma) induced by troglitazone, and we also demonstrated that lupenone
      suppressed the PPARgamma and CCAAT-enhancer-binding protein alpha (C/EBPalpha)
      protein levels. These findings demonstrated that lupenone isolated from A.
      triphylla var. japonica extract effectively inhibited adipocyte differentiation
      through downregulation of related transcription factor, particularly the
      PPARgamma gene.

PMID- 22848029
TI  - Trisomy 18: frequency, types, and prognosis of congenital heart defects in a
      Brazilian cohort.

PMID- 22848030
TI  - On the biological properties of alkynyl phosphine gold(I) complexes.

PMID- 22848031
TI  - Insecticide resistance profiles can be misleading in predicting the survival of
      Myzus persicae genotypes on potato crops following the application of different
      insecticide classes.
AB  - BACKGROUND: The accuracy of predicting the survival of insecticide-resistant
      aphids following the application of commonly used insecticides from the
      carbamate, the pyrethroid, a mix of the two or the neonicotinoid chemical classes
      was evaluated in a potato field in Scotland. Equal proportions of five genotypes
      of the peach-potato aphid, Myzus persicae (Sulzer), with none, resistance to
      dimethyl-carbamates, resistance to pyrethroids or combinations conferring
      resistance to both chemical classes were released into potato field plots. The
      insecticides were sprayed separately onto these plots, the aphid populations were
      analysed after 6-8 days and the process repeated. RESULTS: For each assessment
      after the three separate spray events, plots treated with the carbamate had 48,
      147 and 28%, those treated with pyrethroid 53, 210 and 89%, those treated with
      carbamate/pyrethroid 28, 108 and 64% and those treated with neonicotinoid 43, 55
      and 11% of the numbers of M. persicae by comparison with untreated controls. Only
      the proportions of surviving aphids from the genotype containing no insecticide
      resistance traits and the genotype containing elevated carboxylesterases matched
      ratios predicted from the selective advantage afforded by the resistance traits
      alone. Survival of aphids from the other three genotypes that carried 1-3 of the
      insecticide resistance traits differed from expectations in all cases, possibly
      owing to physiological differences, including their vulnerability to predators
      and hymenopterous parasitoids present at the site and/or their carrying unknown
      insecticide resistance mechanisms. CONCLUSION: Control strategies based on
      knowledge of the genetically determined insecticide resistance profile of an M.
      persicae population alone are insufficient. Hence, other important factors
      contributing to aphid survival under insecticide pressure need to be considered.

PMID- 22848032
TI  - The impact of attention on social functioning in survivors of pediatric acute
      lymphoblastic leukemia and brain tumors.
AB  - BACKGROUND: The cognitive late effects experienced by many survivors of pediatric
      acute lymphoblastic leukemia (ALL) and brain tumors are well-established. The
      most commonly reported deficit is difficulty with attention. Problems with social
      functioning have also been identified, but their relationship with cognitive
      functioning is not well understood. This multi-site, cross-sectional study aimed
      to examine the impact of attention on social functioning. PROCEDURE: Four hundred
      sixty nine survivors of ALL and brain tumors (55% ALL; 57% male) completed study
      procedures, including parent- and teacher-report measures of attention (Conners'
      Rating Scales, Revised) and parent-report of social functioning [Social Skills
      Rating System (SSRS)] as part of their screening evaluation for a large clinical
      trial. Survivors were 12.1 years of age and 4.9 years from the end of treatment
      at the time of study. RESULTS: Results revealed that survivors' parent-reported
      attention problems were uniquely associated with their social functioning,
      relative to known demographic- and treatment-related risk factors. Teacher
      reported attention problems, in contrast, were not, despite a significant
      correlation between the two. Deficits in intelligence and female gender were also
      significantly associated with poor social functioning. CONCLUSIONS: Attention
      problems uniquely impact difficulties with social functioning in survivors of
      pediatric cancer. Future studies will need to further examine the relationship
      between attention and social functioning in survivors, particularly when assessed
      by teacher report. Pediatr Blood Cancer 2012; 59: 1290-1295. (c) 2012 Wiley
      Periodicals, Inc.

PMID- 22848033
TI  - Comparison of 0.5 M gadoterate and 1.0 M gadobutrol in peripheral MRA: a
      prospective, single-center, randomized, crossover, double-blind study.
AB  - PURPOSE: To evaluate the diagnostic efficacy of macrocyclic paramagnetic
      gadolinium (Gd) chelates gadoterate (0.5 mmol/mL) and gadobutrol (1.0 mmol/mL)
      for the diagnosis of clinically significant abdominal/lower limb arterial
      diseases at 3.0T. MATERIALS AND METHODS: This study was conducted as a
      prospective, single-center, randomized, double-blind, intraindividual study
      comparing single dose (0.1 mmol/kg) gadoterate enhanced-MRA (magnetic resonance
      angiography) with gadobutrol enhanced-MRA at 3.0T for their diagnostic potential
      in patients with peripheral artery disease. A total of 20 patients were included
      in this trial. RESULTS: Fourteen patients were eligible for the final efficacy
      analysis. The overall image quality (excellent/more than adequate) was better
      rated with gadoterate than with gadobutrol (100% vs. 78.6%, 100% vs. 92.9%, 100%
      vs. 85.7%, 100% vs. 85.7% for readers 1, 2, 3, 4, respectively). Diagnostic
      confidence was rated high/excellent in 100% (readers 1, 2, and 3) and 92.9%
      (reader 4) with gadoterate compared to 92.9% (readers 1 and 2) and 85.7% (readers
      3 and 4) with gadobutrol. Higher signal-to-noise ratio (SNR) and contrast-to
      noise ratio (CNR) values were obtained for gadobutrol compared to gadoterate
      (26.1/23.4, P = 0.01, and 22.7/20.2, P = 0.01). For the secondary criteria, no
      differences between groups were reported. No adverse events were reported.
      CONCLUSION: Gadobutrol yielded significantly higher SNR/CNR while gadoterate was
      better rated in terms of overall image quality and diagnostic confidence (P >
      0.05).

PMID- 22848034
TI  - Regulation of autocrine fibroblast growth factor-2 signaling by perfusion flow in
      3D human mesenchymal stem cell constructs.
AB  - Perfusion bioreactor systems play a crucial role in mitigating nutrient
      limitation as well as providing biomechanical stimuli and redistributing
      regulatory macromolecules that influence human mesenchymal stem cells (hMSC) fate
      in three-dimensional (3D) scaffolds. As fibroblast growth factor-2 (FGF-2) is
      known to regulate hMSC phenotype, understanding the role of autocrine FGF-2
      signaling in the 3D construct under the different perfusion flow provides
      important insight into an optimal bioreactor design. To investigate FGF-2
      signaling inhibition in hMSC cultured in the porous poly(ethylene terephthalate)
      (PET) scaffolds perfused under two flow configurations, PD173074, an FGFR1
      inhibitor, was added in growth media after 7 day of pre-culture and its impact on
      hMSC proliferation and clonogenicity during the subsequent 7 days of cultivation
      was analyzed. Compared with control constructs in growth media, the addition of
      PD173074 resulted in significant reduction in hMSC proliferation and colony
      formation in both constructs with a more dramatic reduction in the parallel flow
      constructs. The results demonstrate that autocrine FGF-2 plays a significant role
      in 3D scaffold and suggest modulation of the perfusion flow in the bioreactor as
      a strategy to influence autocrine actions and cell fate in the 3D scaffold.

PMID- 22848035
TI  - Case report: Noonan syndrome with multiple giant cell lesions and review of the
      literature.
AB  - Noonan syndrome with multiple giant cell lesions (NS/MGCL) was recently shown to
      be a phenotypic variation within the syndromes of the Ras/MAPK pathway and not an
      independent entity as previously thought. Here we report on a 13-year-old boy
      with a typical phenotype of NS including atrial septal defect, pulmonic stenosis,
      short stature, and combined pectus carinatum/excavatum, pronounced MGCL of both
      jaws, and a de novo mutation in PTPN11, c.236A>G (which predicts p.Q79R).
      Mutations in PTPN11 are the most frequent cause of NS and p.Q79R is a recurrent
      mutation in exon 3. Including this patient, 24 patients with molecularly
      confirmed NS, LEOPARD, or CFC/MGCL syndrome have been reported to date, of these
      21 patients have PTPN11, SOS1, or RAF1 mutations and three have BRAF or MAP2K1
      mutations, confirming that MGCL is a rare complication of the deregulated
      RAS/MAPK pathway. In all patients, the lesions of the mandible and to a lesser
      extent of the maxilla were first noted between ages 2 and 19 years (median 11
      years), and were combined with enlargement of the jaws in 11/24 patients (46%).
      In this case and, with one exception (mutation not reported), all previous cases
      the NS/MGCL was caused by known mutations in the PTPN11, SOS1, RAF1, BRAF1, and
      MAP2K1 genes that were previously reported with RASopathies without MGCL.

PMID- 22848036
TI  - Effects of calcium phosphate endodontic sealers on the behavior of human
      periodontal ligament fibroblasts and MG63 osteoblast-like cells.
AB  - In regard to biological properties of endodontic sealers, there are many
      characteristics that should be considered. The aim of this study was to examine
      the biological effects of new calcium phosphate-based root canal sealers, CAPSEAL
      I and CAPSEAL II (CPS), on human periodontal fibroblast cells by examining the
      expression levels of inflammatory mediators and to compare the effects of CPS on
      the viability and osteogenic potential of human osteoblast MG63 cells compared to
      those of other commercially available calcium phosphate sealers [Apatite Root
      Sealer type I (ARS I) and Apatite Root Sealer III (ARS III); Sankin Kogyo, Tokyo,
      Japan] and a zinc oxide eugenol-based sealer (Pulp Canal Sealer EWT [PCS EWT];
      Kerr, Detroit, MI). The levels of IL-6 in the new CPS group (CAPSEAL I, II) were
      higher than those in the control and all experimental groups at all time points
      after 2 h. TGF-beta1 and FGF-1 levels decreased at 72 h compared to the levels in
      the control, in cells treated with every sealers except ARS I. The new CPS
      sealers showed low cytotoxicity. Reverse transcription polymerase chain reaction
      showed that CAPSEAL I, II, and Apatite Root Sealer type III induced expression of
      early stage markers of differentiation (alkaline phosphatase and osteopontin) at
      7 days. Also, new CPS showed higher mineralized nodule formation at 28 days.
      These results suggest that CAPSEAL I and II facilitate the periapical
      dentoalveolar and alveolar healing by controlling cellular mediators from PDL
      cells and osteoblast differentiation of precursor cells.

PMID- 22848037
TI  - Sour cherry seed kernel extract increases heme oxygenase-1 expression and
      decreases representation of CD3+ TNF-alpha+ and CD3+IL-8+ subpopulations in
      peripheral blood leukocyte cultures from type 2 diabetes patients.
AB  - The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed
      extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of
      potential for uses of SCE in management of inflammatory diseases. Peripheral
      blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight
      healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide
      (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 ug/ml SCE.
      Cultures were evaluated by two-color flow cytometry for percent representation of
      CD3+ IL8+ and CD3+TNF-alpha cells which express interleukin-8 (IL-8), and tumor
      necrosis factor-alpha, (TNF-alpha+) respectively, and by enzyme-linked
      immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced
      by SCE). SCE dosage ranges of 0.5-100 ug/ml in cell cultures significantly
      suppressed LPS-increased CD3+TNF-alpha+ and CD3+IL8+ representation from all
      participants (p < 0.05), with greater pharmacological effect noted in suppression
      of CD3+TNF-alpha+ noted in cells from T2DM patients versus healthy control
      subjects. These effects correlated with increased HO-1 expression in SCE-treated
      PBMC from all subjects (p < 0.05). Since TNF-alpha and IL-8 are
      diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of
      SCE to down-regulate representation of cells that express them suggests potential
      for therapeutic use of SCE in T2DM and other diseases.

PMID- 22848038
TI  - Adjustment and support needs of glioma patients and their relatives: serial
      interviews.
AB  - OBJECTIVE: To understand factors influencing the process of adjustment to a
      diagnosis of glioma. METHODS: Twenty-six patients and 23 relatives took part in
      80 in-depth qualitative interviews conducted at five key stages: before formal
      diagnosis, at start of treatment, on completion of treatment, 6 months post
      treatment, and post bereavement. RESULTS: High levels of distress were reported,
      particularly preceding and following diagnosis. Many participants described lack
      of specific information in the early part of their illness and a lack of clarity
      about what was wrong and what was going to happen next. They often desired more
      procedural information, as well as information about their condition and
      treatments available, although there was variation in the timing of when people
      were ready to hear this. Receiving reassurance and support was essential to
      patients and their relatives to help them come to terms with their illness. This
      need was particularly acute during the early phase of the illness when distress
      and uncertainty were at a peak and lessened over time as people adjusted to their
      illness. CONCLUSIONS: Offering suitable information about what to expect early
      and frequently in a supportive way is much appreciated by patients. There is an
      important balance between ensuring that patients and their families are fully
      informed and fostering adaptive coping that allows for hope.

PMID- 22848039
TI  - Bioreactor environment-sensitive sentinel genes as novel metrics for cell culture
      scale-down comparability.
AB  - Scale-down of bioreactors is currently done based on matching one or more
      measurable parameters such as k(L) a and P/V, which could result in insufficient
      process comparability. Currently, there is a lack of genomic translational
      studies in cell culture scale-down, which could help delineate measurable
      cellular attributes for improved scale-down. In this study, we scaled-down from a
      typical bench-scale 5-L bioreactor to a novel high-throughput 35-mL
      minibioreactor based on matching oxygen transfer rate, which resulted in cell
      growth and product-related discrepancies using Sp2/0 cells. Performing DNA
      microarrays on time-course samples from both systems, we identified ~200
      differentially expressed transcripts, presumably because of bioreactor aeration
      and mixing differences with scale-down. Evaluating these transcripts for
      bioreactor-relevant cellular functions such as oxidative stress response and DNA
      damage response, we chose 18 sentinel genes based on their degree of difference
      and functionality, which we further verified by quantitative real-time polymerase
      chain reaction (qRT-PCR). Tracking the differential expression of Sod1, Apex1,
      and Odc1 genes, we were able to correlate sparging-related damage and poor
      mixing, as possible causes for physiological changes such as prolonged culture in
      minibioreactors. Additionally, to verify our sentinel gene findings, we performed
      follow-up improved scale-down studies based on gene analysis and measured
      transcriptomic changes. As a result, qRT-PCR-based genomic profiles and cell
      growth profiles showed better convergence between the improved minibioreactor
      conditions and the model 5-L bioreactor. Our results broadly show that based on
      the knowledge from transcriptomic changes of sentinel gene profiles, it is
      possible to improve bioreactor scale-down for more comparable processes.

PMID- 22848040
TI  - Quality of life in childhood immune thrombocytopenia: international validation of
      the kids' ITP tools.
AB  - BACKGROUND: The Kids ITP Tools (KIT) is a disease-specific measure of health
      related quality of life for children with immune thrombocytopenia (ITP). To
      facilitate use in international trials it has been cross-culturally adapted for
      France, Germany, the United Kingdom and Uruguay. This study assessed the validity
      and reliability of the translated KIT in comparison to generic quality of life
      measures. METHODS: Children 2-18 years of age with ITP and their parents were
      recruited in France, Germany, the United Kingdom and Uruguay. Participants
      completed the KIT, PedsQL and KINDL. We examined the Pearson's correlation
      between these measures for our pooled sample and estimated the reliability over a
      2-week time period. Findings were further explored by country. RESULTS: A total
      of 127 families (81 children self-reported) participated. Mean child-reported
      scores were: KIT 74.3 (SD = 15.3), PedsQL 81.3 (SD = 13.0), and KINDL 70.5 (SD =
      14.3). Corresponding mean parent proxy-reported scores were: 70.6 (SD = 18.1),
      75.7 (SD = 16.8) and 72.3 (SD = 12.7), respectively. Correlation between KIT and
      the generic measures was consistent with our a priori hypothesis (PedsQL r =
      0.54, KINDL r = 0.48, both P < 0.0001). Child KIT scores for newly diagnosed ITP
      patients were significantly lower than for chronic ITP patients (67.3 vs. 77.3; P
      = 0.005). There was a significant correlation (P < 0.001) between the child and
      parent proxy KIT scores (ICC = 0.52). Child KIT test-retest reliability was
      acceptable at 0.71. CONCLUSIONS: The cross-culturally translated KIT is valid and
      reliable with acceptable correlation to the PedsQL and KINDL. There is a
      significant difference in child self-reported KIT scores between newly diagnosed
      and chronic ITP.

PMID- 22848041
TI  - Neural stimulation on human bone marrow-derived mesenchymal stem cells by
      extremely low frequency electromagnetic fields.
AB  - Adult stem cells are considered multipotent. Especially, human bone marrow
      derived mesenchymal stem cells (hBM-MSCs) have the potential to differentiate
      into nerve type cells. Electromagnetic fields (EMFs) are widely distributed in
      the environment, and recently there have been many reports on the biological
      effects of EMFs. hBM-MSCs are weak and sensitive pluripotent stem cells,
      therefore extremely low frequency-electromagnetic fields (ELF-EMFs) could be
      affect the changes of biological functions within the cells. In our experiments,
      ELF-EMFs inhibited the growth of hBM-MSCs in 12 days exposure. Their gene level
      was changed and expression of the neural stem cell marker like nestin was
      decreased but the neural cell markers like MAP2, NEUROD1, NF-L, and Tau were
      induced. In immunofluorescence study, we confirmed the expression of each protein
      of neural cells. And also both oligodendrocyte and astrocyte related proteins
      like O4 and GFAP were expressed by ELF-EMFs. We suggest that EMFs can induce
      neural differentiation in BM-MSCs without any chemicals or differentiation
      factors.

PMID- 22848042
TI  - Affective state and cognitive functioning in patients with intracranial tumors:
      validity of the neuropsychological baseline assessment.
AB  - OBJECTIVES: The aim of this paper is to investigate the relationship between the
      affective and cognitive states of neurooncological patients prior to the
      neurosurgical treatment to assess associations between distress levels and
      neuropsychological test performance in this sample and setting. METHODS: The
      prospective study population consists of 172 patients. Patients were studied
      preoperatively with a comprehensive test battery consisting of a variety of
      affective and cognitive measures. Psychological instruments included the Hospital
      Anxiety and Depression Scale, the Amsterdam Preoperative Anxiety and Information
      Scale, and the Acute Stress Disorder Scale. RESULTS: Factor analysis revealed two
      factors representing subjective affective functioning: whereas one reflects the
      patients' more general emotional state (Hospital Anxiety and Depression Scale,
      Acute Stress Disorder Scale), the second reflects anxiety specifically related to
      the neurosurgical procedure (Amsterdam Preoperative Anxiety and Information
      Scale). After age and education have been accounted for via linear regression
      analyses, affect did not contribute to cognitive performance in any of the
      cognitive domains in the whole patient sample. However, in patients with extreme
      levels of psychiatric morbidity, there was evidence for distinct cognitive
      morbidity consistent with previous research. CONCLUSIONS: Our results suggest
      that, for a large variety of widely used neuropsychological measures and for most
      neurooncological patients, the preoperative neuropsychological baseline
      assessment can be considered valid and dependable. In patients with extreme
      levels of distress, however, distinct cognitive domains might be differentially
      affected.

PMID- 22848043
TI  - Postnatal development of electrophysiological properties of principal neurons in
      the rat basolateral amygdala.
AB  - The basolateral amygdala (BLA) is critically involved in the pathophysiology of
      psychiatric disorders, which often emerge during brain development. Several
      studies have characterized postnatal changes to the morphology and biochemistry
      of BLA neurons, and many more have identified sensitive periods of emotional
      maturation. However, it is impossible to determine how BLA development
      contributes to emotional development or the aetiology of psychiatric disorders
      because no study has characterized the physiological maturation of BLA neurons.
      We addressed this critical knowledge gap for the first time using whole-cell
      patch clamp recording in rat BLA principal neurons to measure
      electrophysiological properties at postnatal day (P)7, P10, P14, P21, P28 and
      after P35. We show that intrinsic properties of these neurons undergo significant
      transitions before P21 and reach maturity around P28. Specifically, we observed
      significant reductions in input resistance and membrane time constant of nearly
      10-and 4-fold, respectively, from P7 to P28. The frequency selectivity of these
      neurons to input also changed significantly, with peak resonance frequency
      increasing from 1.0 Hz at P7 to 5.7 Hz at P28. In the same period, maximal firing
      frequency significantly increased and doublets and triplets of action potentials
      emerged. Concomitantly, individual action potentials became significantly faster,
      firing threshold hyperpolarized 6.7 mV, the medium AHP became faster and
      shallower, and a fast AHP emerged. These results demonstrate neurons of the BLA
      undergo vast change throughout postnatal development, and studies of emotional
      development and treatments for juvenile psychiatric disorders should consider the
      dynamic physiology of the immature BLA.

PMID- 22848044
TI  - A murine experimental model for the mechanical behaviour of viable right
      ventricular myocardium.
AB  - Although right-ventricular function is an important determinant of cardio
      pulmonary performance in health and disease, right ventricular myocardium
      mechanical behaviour has received relatively little attention. We present a novel
      experimental method for quantifying the mechanical behaviour of transmurally
      intact, viable right-ventricular myocardium. Seven murine right ventricular free
      wall (RVFW) specimens were isolated and biaxial mechanical behaviour measured,
      along with quantification of the local transmural myofibre and collagen fibre
      architecture. We developed a complementary strain energy function based method to
      capture the average biomechanical response. Overall, murine RVFW revealed
      distinct mechanical anisotropy. The preferential alignment of the myofibres and
      collagen fibres to the apex-to-outflow-tract direction was consistent with this
      also being the mechanically stiffer axis. We also observed that the myofibre and
      collagen fibre orientations were remarkably uniform throughout the entire RVFW
      thickness. Thus, our findings indicate a close correspondence between the tissue
      microstructure and biomechanical behaviour of the RVFW myocardium, and are a
      first step towards elucidating the structure-function of non-contracted murine
      RVFW myocardium in health and disease.

PMID- 22848046
TI  - Rapid, in situ detection of Agrobacterium tumefaciens attachment to leaf tissue.
AB  - Attachment of the plant pathogen Agrobacterium tumefaciens to host plant cells is
      an early and necessary step in plant transformation and agroinfiltration
      processes. However, bacterial attachment behavior is not well understood in
      complex plant tissues. Here we developed an imaging-based method to observe and
      quantify A. tumefaciens attached to leaf tissue in situ. Fluorescent labeling of
      bacteria with nucleic acid, protein, and vital dyes was investigated as a rapid
      alternative to generating recombinant strains expressing fluorescent proteins.
      Syto 16 green fluorescent nucleic acid stain was found to yield the greatest
      signal intensity in stained bacteria without affecting viability or infectivity.
      Stained bacteria retained the stain and were detectable over 72 h. To demonstrate
      in situ detection of attached bacteria, confocal fluorescent microscopy was used
      to image A. tumefaciens in sections of lettuce leaf tissue following vacuum
      infiltration with labeled bacteria. Bacterial signals were associated with plant
      cell surfaces, suggesting detection of bacteria attached to plant cells.
      Bacterial attachment to specific leaf tissues was in agreement with known leaf
      tissue competencies for transformation with Agrobacterium. Levels of bacteria
      attached to leaf cells were quantified over time post-infiltration. Signals from
      stained bacteria were stable over the first 24 h following infiltration but
      decreased in intensity as bacteria multiplied in planta. Nucleic acid staining of
      A. tumefaciens followed by confocal microscopy of infected leaf tissue offers a
      rapid, in situ method for evaluating attachment of A. tumefaciens' to plant
      expression hosts and a tool to facilitate management of transient expression
      processes via agroinfiltration.

PMID- 22848047
TI  - Cortical circuitry associated with reflex cardiovascular control in humans: does
      the cortical autonomic network "speak" or "listen" during cardiovascular arousal.
AB  - Beginning with clinical evidence of fatal cardiac arrhythmias in response to
      severe stress, in epileptic patients, and following stroke, the role of the
      cerebral cortex in autonomic control of the cardiovascular system has gained both
      academic and clinical interest. Studies in anesthetized rodents have exposed the
      role of several forebrain regions involved in cardiovascular control. The
      introduction of functional neuroimaging techniques has enabled investigations
      into the conscious human brain to illuminate the temporal and spatial activation
      patterns of cortical regions that are involved with cardiovascular control
      through the autonomic nervous system. This symposia report emphasizes the
      research performed by the authors to understand the functional organization of
      the human forebrain in cardiovascular control during physical stressors of
      baroreceptor unloading and handgrip exercise. The studies have exposed important
      associations between activation patterns of the insula cortex, dorsal anterior
      cingulate, and the medial prefrontal cortex and cardiovascular adjustments to
      physical stressors. Furthermore, these studies provide functional anatomic
      evidence that sensory signals arising from baroreceptors and skeletal muscle are
      represented within the insula cortex and the medial prefrontal cortex, in
      addition to the sensory cortex. Thus, the cortical pathways subserving reflex
      cardiovascular control integrate viscerosensory inputs with outgoing traffic that
      modulates the autonomic nervous system.

PMID- 22848045
TI  - The time course of the adaptations of human muscle proteome to bed rest and the
      underlying mechanisms.
AB  - In order to get a comprehensive picture of the complex adaptations of human
      skeletal muscle to disuse and further the understanding of the underlying
      mechanisms, we participated in two bed rest campaigns, one lasting 35 days and
      one 24 days. In the first bed rest (BR) campaign, myofibrillar proteins,
      metabolic enzymes and antioxidant defence systems were found to be down-regulated
      both post-8 days and post-35 days BR by proteomic analysis of vastus lateralis
      muscle samples from nine subjects. Such profound alterations occurred early (post
      8 days BR), before disuse atrophy developed, and persisted through BR (post-35
      days BR). To understand the mechanisms underlying the protein adaptations
      observed, muscle biopsies from the second bed rest campaign (nine subjects) were
      used to evaluate the adaptations of master controllers of the balance between
      muscle protein breakdown and muscle protein synthesis (MuRF-1 and atrogin-1; Akt
      and p70S6K), of autophagy (Beclin-1, p62, LC3, bnip3, cathepsin-L), of expression
      of antioxidant defence systems (NRF2) and of energy metabolism (PGC-1alpha, SREBP
      1, AMPK). The results indicate that: (i) redox imbalance and remodelling of
      muscle proteome occur early and persist through BR; (ii) impaired energy
      metabolism is an early and persistent phenomenon comprising both the oxidative
      and glycolytic one; (iii) although both major catabolic systems, ubiquitin
      proteasome and autophagy, could contribute to the progression of atrophy late
      into BR, a decreased protein synthesis cannot be ruled out; (iv) a decreased PGC
      1alpha, with the concurrence of SREBP-1 up-regulation, is a likely trigger of
      metabolic impairment, whereas the AMPK pathway is unaltered.

PMID- 22848048
TI  - Engineering the acceptor specificity of trehalose phosphorylase for the
      production of trehalose analogs.
AB  - Trehalose (alpha-D-glucopyranosyl-(1,1)-alpha-D-glucopyranoside) is widely used
      in the food industry, thanks to its protective effect against freezing and
      dehydration. Analogs of trehalose have the additional benefit that they are not
      digested and thus do not contribute to our caloric intake. Such trehalose analogs
      can be produced with the enzyme trehalose phosphorylase, when it is applied in
      the reverse, synthetic mode. Despite the enzyme's broad acceptor specificity, its
      catalytic efficiency for alternative monosaccharides is much lower than for
      glucose. For galactose, this difference is shown here to be caused by a lower
      K(m) whereas the k(cat) for both substrates is equal. Consequently, increasing
      the affinity was attempted by enzyme engineering of the trehalose phosphorylase
      from Thermoanaerobacter brockii, using both semirational and random mutagenesis.
      While a semirational approach proved unsuccessful, high-throughput screening of
      an error-prone PCR library resulted in the discovery of three beneficial
      mutations that lowered K(m) two- to three-fold. In addition, it was found that
      mutation of these positions also leads to an improved catalytic efficiency for
      mannose and fructose, suggesting their involvement in acceptor promiscuity.
      Combining the beneficial mutations did not further improve the affinity, and even
      resulted in a decreased catalytic activity and thermostability. Therefore, enzyme
      variant R448S is proposed as new biocatalyst for the industrial production of
      lactotrehalose (alpha-D-glucopyranosyl-(1,1)-alpha-D-galactopyranoside).

PMID- 22848049
TI  - In-depth analysis of low abundant proteins in bovine colostrum using different
      fractionation techniques.
AB  - Bovine colostrum is well known for its large content of bioactive components and
      its importance for neonatal survival. Unfortunately, the colostrum proteome is
      complicated by a wide dynamic range, because of a few dominating proteins that
      hamper sensitivity and proteome coverage achieved on low abundant proteins.
      Moreover, the composition of colostrum is complex and the proteins are located
      within different physical fractions that make up the colostrum. To gain a more
      exhaustive picture of the bovine colostrum proteome and gather information on
      protein location, we performed an extensive pre-analysis fractionation of
      colostrum prior to 2D-LC-MS/MS analysis. Physical and chemical properties of the
      proteins and colostrum were used alone or in combination for the separation of
      proteins. ELISA was used to quantify and verify the presence of proteins in
      colostrum. In total, 403 proteins were identified in the nonfractionated
      colostrum (NF) and seven fractions (F1-F7) using six different fractionation
      techniques. Fractionation contributed with 69 additional proteins in the fluid
      phase compared with NF. Different fractionation techniques each resulted in
      detection of unique subsets of proteins. Whey production by high-speed
      centrifugation contributed most to detection of low abundant proteins. Hence,
      prefractionation of colostrum prior to 2D-LC-MS/MS analysis expanded our
      knowledge on the presence and location of low abundant proteins in bovine
      colostrum.

PMID- 22848050
TI  - Protein profiling of epidermal bladder cells from the halophyte Mesembryanthemum
      crystallinum.
AB  - Plant epidermal trichomes are as varied in morphology as they are in function. In
      the halophyte Mesembryanthemum crystallinum, specialized trichomes called
      epidermal bladder cells (EBC) line the surface of leaves and stems, and increase
      dramatically in size and volume upon plant salt-treatment. These cells have been
      proposed to have roles in plant defense and UV protection, but primarily in
      sodium sequestration and as water reservoirs. To gain further understanding into
      the roles of EBC, a cell-type-specific proteomics approach was taken in which
      precision single-cell sampling of cell sap from individual EBC was combined with
      shotgun peptide sequencing (LC-MS/MS). Identified proteins showed diverse
      biological functions and cellular locations, with a high representation of
      proteins involved in H(+)-transport, carbohydrate metabolism, and photosynthesis.
      The proteome of EBC provides insight into the roles of these cells in ion and
      water homeostasis and raises the possibility that they are photosynthetically
      active and functioning in Crassulacean acid metabolism.

PMID- 22848051
TI  - Identification of proteins associated with malting quality in a subset of wild
      barley introgression lines.
AB  - Malted barley is an important ingredient used in the brewing and distilling
      industry worldwide. In this study, we used a proteomics approach to investigate
      the biochemical function of previously identified quantitative trait loci (QTLs)
      on barley chromosomes 1H and 4H that influence malting quality. Using a subset of
      barley introgression lines containing wild barley (Hordeum vulgare ssp.
      spontaneum) alleles at these QTLs, we validated that wild barley alleles at the
      chromosome 1H QTL reduced overall malting quality, whereas wild barley alleles at
      the chromosome 4H QTL improved the malting quality parameters alpha-amylase
      activity, VZ45, and Kolbach index compared to the control genotype Scarlett. 2DE
      was used to detect changes in protein expression during the first 72 h of
      micromalting associated with these QTLs. In total, 16 protein spots showed a
      significant change in expression between the introgression lines and Scarlett, of
      which 14 were successfully identified with MS. Notably, the wild barley alleles
      in the line containing the chromosome 4H QTL showed a sixfold increased
      expression of a limit dextrinase inhibitor. The possible role of the identified
      proteins in malting quality is discussed. The knowledge gained will assist
      ongoing research toward cloning the genes underlying these important QTL.

PMID- 22848052
TI  - Does evidence lead to policy change?

PMID- 22848053
TI  - Better safe than sorry.

PMID- 22848054
TI  - Getting in early: identification of risk in early childhood.

PMID- 22848055
TI  - Why screening and treating 3-year-olds for mental health problems is not such a
      good idea.

PMID- 22848056
TI  - Checking healthy kids.

PMID- 22848057
TI  - Would a universal check of 3-year-olds prevent or create childhood mental health
      problems?

PMID- 22848058
TI  - Medical partisans? Why doctors need conflicting interests.

PMID- 22848059
TI  - Minding the gap: Commentary on 'Policy and service development implications of
      the second Australian National Survey of High Impact Psychosis (SHIP)'.

PMID- 22848060
TI  - Counting the cost: Commentary on a systematic review of cost of early
      intervention in psychosis.

PMID- 22848061
TI  - Psychosis risk, disorder and diagnosis: deeper into the mud.

PMID- 22848062
TI  - Peripheral oedema in quetiapine therapy.

PMID- 22848063
TI  - An MBoC favorite: Fibronectin/integrin interaction induces tyrosine
      phosphorylation of a 120-kDa protein.

PMID- 22848064
TI  - An MBoC favorite: ARF is required for maintenance of yeast Golgi and endosome
      structure and function.

PMID- 22848066
TI  - How should we train the upper limbs?

PMID- 22848065
TI  - A simple guide to biochemical approaches for analyzing protein-lipid
      interactions.
AB  - Eukaryotic cells contain many different membrane compartments with characteristic
      shapes, lipid compositions, and dynamics. A large fraction of cytoplasmic
      proteins associate with these membrane compartments. Such protein-lipid
      interactions, which regulate the subcellular localizations and activities of
      peripheral membrane proteins, are fundamentally important for a variety of cell
      biological processes ranging from cytoskeletal dynamics and membrane trafficking
      to intracellular signaling. Reciprocally, many membrane-associated proteins can
      modulate the shape, lipid composition, and dynamics of cellular membranes.
      Determining the exact mechanisms by which these proteins interact with membranes
      will be essential to understanding their biological functions. In this Technical
      Perspective, we provide a brief introduction to selected biochemical methods that
      can be applied to study protein-lipid interactions. We also discuss how important
      it is to choose proper lipid composition, type of model membrane, and biochemical
      assay to obtain reliable and informative data from the lipid-interaction
      mechanism of a protein of interest.

PMID- 22848067
TI  - Outcomes associated with a negotiated asthma treatment plan.
AB  - Negotiated treatment plans are increasingly recommended in asthma clinical care.
      However, limited data are available to indicate whether this more patient-engaged
      process results in improved health outcomes. The aim of this study was to
      determine the associations between the presence of a negotiated treatment plan
      and the outcomes related to adherence to the medical regimen, symptom control,
      and health care use. The focus of the study was on women, the subgroup of adult
      patients, who are most vulnerable for negative asthma outcomes. Data were
      collected by telephone interview and medical record review from 808 women
      diagnosed with asthma at baseline, first year, and second year follow-up.
      Associations were examined between the presence of a negotiated treatment plan at
      baseline and subsequent asthma outcomes. Women with a negotiated treatment plan
      reported more adherent to prescribed asthma medicines (odds ratio (OR) = 2.41,
      95% confidence interval (CI) = (1.82, 3.19)) and those with a plan and using oral
      steroids at baseline had less oral steroid use at follow-up (OR = 0.21, 95% CI =
      (0.05, 0.93)). Women with a negotiated plan also had more days (17%, 95% CI = (8,
      27)) and nights (31%, 95% CI = (16, 48)) with symptoms than those without such a
      plan. No differences in hospitalizations, emergency department visits, or urgent
      physician office visits were noted between the groups. Patients with higher
      education levels were more likely to have a negotiated treatment plan. Negotiated
      treatment plans appear to have achieved greater adherence to prescribed asthma
      medicines and less need for oral steroids but were not related to fewer symptoms
      of asthma or reductions in urgent health care use. Additional strategies may be
      needed to reduce symptom and health services utilization outcomes.

PMID- 22848068
TI  - Chronic obstructive pulmonary disease and comorbidities through the eyes of the
      patient.
AB  - Patient's attitudes and illness beliefs have shown to be of great importance in
      chronic obstructive pulmonary disease (COPD). As former qualitative research has
      mainly focused on patients with end-stage COPD, who are recruited within hospital
      or pulmonary rehabilitation settings, and excluding patients with disabling
      comorbidities, this study specifically aims to explore the perspectives of
      patients with COPD and comorbidities in primary care. This study was designed as
      a qualitative, explorative study using open patient interviews. The study was
      conducted at three primary care practices, East Flanders, Belgium. A total number
      of seven patients, diagnosed with COPD and given a minimum score of 2 on the
      Charlson Comorbidity Index were included. In-depth interviews were recorded and
      transcribed verbatim. Thematic analysis was deductive using NVivo software.
      Researchers' triangulation was performed. Participants show high adaptation
      capabilities and report quite positively about their functional status, with an
      emphasis on social participation and partnership. Knowledge of the causes and
      consequences of COPD appears rather limited, and participants predominantly show
      an external locus of control in relation to the reported factors influencing the
      disease and strategies for self-management. Patients with COPD with comorbidity
      integrate their illness and symptoms into their lives. However, a lack of
      knowledge and education may leave them more anxious and more dependent on health
      care than necessary. Our results indicate that health care workers should adopt a
      positive approach toward patient's functioning and empower and inform their
      patients. We believe that chronic care for patients with COPD should provide
      personalized rehabilitation taking into account individual patient
      characteristics and self-management and coping attitudes. We believe that there
      is a generic core to be identified, which can tackle both COPD and comorbidities.
      Further research is mandatory to develop these generic programs focusing on
      patients with complicated needs. Primary care can provide the setting for
      exploration.

PMID- 22848069
TI  - Excessive wave reflections on admission predict post-discharge events in patients
      hospitalized due to acute heart failure.
AB  - AIMS: The role of wave reflections in the pathogenesis of acute heart failure
      syndrome (AHFS) remains unclear. The present study investigated the long-term
      prognostic values of the carotid augmentation index (cAI), carotid augmented
      pressure (cAP), amplitude of the reflected pressure wave from a decomposed
      carotid pressure wave (Pb), and carotid pulse pressure (PP) on admission in
      patients hospitalized due to AHFS. METHODS AND RESULTS: A total of 120 patients
      (72 +/- 14 years, 83.3% men) hospitalized due to AHFS (55.8% with systolic heart
      failure) were enrolled. Measures of cAI, cAP, Pb, carotid PP, and carotid-femoral
      pulse wave velocity (cf-PWV) by tonometry and thoracic fluid content (TFC) by
      impedance cardiography were obtained within 24 h of admission. N-terminal pro
      brain natriuretic peptide (NT-proBNP) levels were determined before discharge.
      Patients were followed up for a median of 601 days, accruing 66 adverse events
      including re-hospitalization for heart failure, non-fatal myocardial infarction,
      non-fatal stroke, and death. In univariate Cox analysis, all measures
      significantly predicted post-discharge events (all P < 0.05). In multivariate
      analysis, cAP [hazard ratio per SD and 95% confidence interval: 1.32 (1.051
      1.67), P = 0.017], Pb [1.44 (1.13-1.84), P = 0.004] and carotid PP [1.35 (1.05
      1.73), P = 0.019], but not cAI, TFC, or cf-PWV, significantly independently
      predicted events with adjustments for age, estimated glomerular filtration rate,
      haemoglobin, and NT-proBNP. CONCLUSION: On-admission measures of wave reflection
      magnitude, including cAP, Pb, and carotid PP, may be useful for predicting long
      term outcomes in AHFS patients. The results support a major role for wave
      reflection in the pathogenesis of AHFS.

PMID- 22848070
TI  - Deciphering the relationship between mating system and the molecular evolution of
      the pheromone and receptor genes in Neurospora.
AB  - Here, we present a study of the molecular evolution of the pheromone receptor
      genes (pre-1 and pre-2) in Neurospora taxa with different mating systems. We
      focus on comparisons between heterothallic and homothallic taxa, reproducing
      sexually by outcrossing and by intrahaploid selfing, respectively. Our general
      aim was to use a phylogenetic framework to investigate whether the evolutionary
      trajectory of the pheromone and receptor genes in Neurospora differs between
      heterothallic and homothallic taxa, and among the homothallic lineages/clades
      previously indicated to represent independent switches from heterothallism to
      homothallism in the evolutionary history of the genus. We complemented molecular
      evolution analyses with an expression study of the pre genes and their upstream
      regulators, the mating-type (mat) genes, in homothallic taxa. Our analyses
      suggest that the pheromone receptor gene pre-1 is functionally conserved in both
      heterothallic and homothallic taxa. Moreover, we found evidence of positive
      selection for a small fraction of codons in the cytoplasmic signal-transducing C
      terminal region of the protein PRE-1. Distribution of positively selected codons
      differs between heterothallic and homothallic groups, suggesting functional
      divergence associated with mating system. The gene pre-2 was shown to evolve
      under high selective constraints, with no strong evidence for positive selection.
      Although our data suggest that both pre-1 and pre-2 are overall functional in
      homothallic taxa, individual taxa display frame-shift mutations causing premature
      stop codons, which might indicate loss of function. Transcriptional patterns of
      pre and mat genes in six homothallic taxa, selected to represent six different
      switches from heterothallism to homothallism, do not support a universal pattern
      of regulation of these genes during reproductive tissue development. Taken
      together, our analyses suggest that the pheromone receptor genes pre-1 and pre-2
      are in general functional in homothallic Neurospora taxa, in contrast with the
      situation for the mat genes that are generally degenerate in these taxa.

PMID- 22848071
TI  - Novel incentive-based approaches to adherence.
AB  - BACKGROUND: Adherence to medications for chronic conditions is often very low,
      limiting the benefit to patients, even when the medications are effective and
      have favorable side effect profiles. PURPOSE: This article reviews some of the
      prior work on treatment adherence, introduces novel concepts from behavioral
      economics that can be used to design interventions to improve adherence, and
      proposes new approaches for clinical trials. METHODS: Relevant experience of the
      authors and insights from the literature were combined to identify key issues and
      propose methodological improvements. Specific examples regarding adherence to
      warfarin are provided. RESULTS: Several new approaches to trial design can be
      effectively applied in the context of medication adherence. These include
      tailored intervention strategies and sequential multiple assignment randomized
      trial (SMART) designs. LIMITATIONS: While we have proposed to use these new
      approaches for ongoing studies of adherence in behavioral health, practical
      experience with their application is still somewhat limited. CONCLUSIONS:
      Behavioral economics offer a variety of concepts that, when used in the design of
      interventions to improve adherence, may be more successful than traditional
      approaches. New clinical trial designs can also be adopted to improve the
      efficiency of studies that assess these approaches.

PMID- 22848072
TI  - Using audit information to adjust parameter estimates for data errors in clinical
      trials.
AB  - BACKGROUND: Audits are often performed to assess the quality of clinical trial
      data, but beyond detecting fraud or sloppiness, the audit data are generally
      ignored. In an earlier study, using data from a nonrandomized study, Shepherd and
      Yu developed statistical methods to incorporate audit results into study
      estimates and demonstrated that audit data could be used to eliminate bias.
      PURPOSE: In this article, we examine the usefulness of audit-based error
      correction methods in clinical trial settings where a continuous outcome is of
      primary interest. METHODS: We demonstrate the bias of multiple linear regression
      estimates in general settings with an outcome that may have errors and a set of
      covariates for which some may have errors and others, including treatment
      assignment, are recorded correctly for all subjects. We study this bias under
      different assumptions, including independence between treatment assignment,
      covariates, and data errors (conceivable in a double-blinded randomized trial)
      and independence between treatment assignment and covariates but not data errors
      (possible in an unblinded randomized trial). We review moment-based estimators to
      incorporate the audit data and propose new multiple imputation estimators. The
      performance of estimators is studied in simulations. RESULTS: When treatment is
      randomized and unrelated to data errors, estimates of the treatment effect using
      the original error-prone data (i.e., ignoring the audit results) are unbiased. In
      this setting, both moment and multiple imputation estimators incorporating audit
      data are more variable than standard analyses using the original data. In
      contrast, in settings where treatment is randomized but correlated with data
      errors and in settings where treatment is not randomized, standard treatment
      effect estimates will be biased. And in all settings, parameter estimates for the
      original, error-prone covariates will be biased. The treatment and covariate
      effect estimates can be corrected by incorporating audit data using either the
      multiple imputation or moment-based approaches. Bias, precision, and coverage of
      confidence intervals improve as the audit size increases. LIMITATIONS: The extent
      of bias and the performance of methods depend on the extent and nature of the
      error as well as the size of the audit. This study only considers methods for the
      linear model. Settings much different than those considered here need further
      study. CONCLUSIONS: In randomized trials with continuous outcomes and treatment
      assignment independent of data errors, standard analyses of treatment effects
      will be unbiased and are recommended. However, if treatment assignment is
      correlated with data errors or other covariates, naive analyses may be biased. In
      these settings, and when covariate effects are of interest, approaches for
      incorporating audit results should be considered.

PMID- 22848073
TI  - Reconnecting to the endpoint of atrial fibrillation ablation: should we mind the
      gaps?

PMID- 22848074
TI  - Efficacy and safety of nitroglycerin for preventing venous spasm during contrast
      guided axillary vein puncture for pacemaker or defibrillator leads implantation.
AB  - AIMS: We investigated the efficacy and safety of nitroglycerin for preventing
      venous spasm during contrast-guided axillary vein puncture for pacemaker or
      defibrillator leads implantation. METHODS AND RESULTS: A total of 40 consecutive
      patients referred for contrast-guided axillary vein puncture for pacemaker or
      defibrillator implantations were included in the study. Patients were randomly
      assigned to control group and nitroglycerin group. Patients in the nitroglycerin
      group were given 200 ug (2 mL) nitroglycerin via ipsilateral peripheral vein
      about 3 min before puncture. The degree of venous spasm was evaluated by the
      reduction in lumen calibre of the axillary vein after puncture. Mild venous spasm
      and severe venous spasm were defined as a reduction in lumen calibre of 50-90%
      and >= 90%, respectively. The mean degree of venous spasm of axillary vein was
      lower in the nitroglycerin group than in the control group (23.0 +/- 22.3 vs.
      45.5 +/- 33.6%, P = 0.018). The incidence of mild or severe venous spasm was
      lower in the nitroglycerin group than in the control group (3/20 vs. 11/20, P =
      0.019). In the nitroglycerin group, the systolic blood pressure had a significant
      decrease after puncture (129.5 +/- 23.7 vs. 143.0 +/- 24.1 mmHg, P = 0.003).
      There was no hypotension and other adverse reaction of nitroglycerin in the
      nitroglycerin group. CONCLUSION: Intravenous nitroglycerin is effective and safe
      for preventing venous spasm during contrast-guided axillary vein puncture for
      pacemaker or defibrillator leads implantation.

PMID- 22848075
TI  - Occurrence of phrenic nerve stimulation in cardiac resynchronization therapy
      patients: the role of left ventricular lead type and placement site.
AB  - AIMS: Unwanted phrenic nerve stimulation (PNS) has been reported in ~1 in 4
      patients undergoing left ventricular (LV) pacing. The occurrence of PNS over mid
      term follow-up and the significance of PNS are less certain. METHODS AND RESULTS:
      Data from 1307 patients enrolled in pre-market studies of LV leads manufactured
      by Medtronic (models 4193 and 4195 unipolar, 4194, 4196, 4296, and 4396 bipolar)
      were pooled. Left ventricular lead location was recorded at implant using a
      common classification scheme. Phrenic nerve stimulation symptoms were either
      spontaneously reported or identified at scheduled follow-up visits. A PNS-related
      complication was defined as PNS resulting in invasive intervention or the
      termination of LV pacing. Average follow-up was 14.9 months (range 0.0-46.6).
      Phrenic nerve stimulation symptoms occurred in 169 patients (12.9%). Phrenic
      nerve stimulation-related complications occurred in 21 of 1307 patients (1.6%);
      16 of 738 (2.2%) in the unipolar lead studies, and 5 of 569 (0.9%) in the bipolar
      lead studies (P = 0.08). Phrenic nerve stimulation was more frequent at middle
      lateral/posterior, and apical LV sites (139/1010) vs. basal
      posterior/lateral/anterior, and middle-anterior sites (20/297; P= 0.01). As
      compared with an anterior LV lead position, a lateral LV pacing site was
      associated with over a four-fold higher risk of PNS (P= 0.005) and an apical LV
      pacing site was associated with over six-fold higher risk of PNS (P= 0.001).
      CONCLUSION: Phrenic nerve stimulation occurred in 13% of patients undergoing LV
      lead placement and was more common at mid-lateral/posterior, and LV apical sites.
      Most cases (123/139; 88%) of PNS were mitigated via electrical reprogramming,
      without the need for invasive intervention.

PMID- 22848076
TI  - Clinical markers of organ dysfunction associated with increased 1-year mortality
      post-implantable cardioverter defibrillator implantation.
AB  - AIMS: Guidelines from the ESC and ACC/AHA recommend implantable cardioverter
      defibrillators (ICDs) be implanted in clinically indicated patients with a
      reasonable expectation of >1 year survival. Our study aimed to assess if selected
      clinical markers of organ dysfunction were associated with increased 1-year
      mortality despite ICD therapy. METHODS AND RESULTS: We retrospectively studied
      283 patients with de novo ICDs implanted for primary or secondary prevention in
      ischaemic heart disease and dilated cardiomyopathy. We investigated the
      association of the following clinical markers of organ dysfunction with 1 year
      mortality: liver dysfunction (aspartate transaminase/alanine transaminase >= 3*
      upper limit of normal or prothrombin time/international normalized ratio >= 1.5
      in the absence of anticoagulation), respiratory dysfunction (recent mechanical
      ventilation within 3 months prior to ICD implant), renal dysfunction (creatinine
      >=150 umol/L or glomerular filtration rate <= 30 mL/min/1.73 m(2)), anaemia (Hb
      <= 100 g/L), and prior cerebral vascular injury. With no organ dysfunction, 1
      year mortality was 1.9%. In the presence of a single organ dysfunction, mortality
      was increased to 14.3%. With two or more markers of organ dysfunction mortality
      was 38.1% at 1 year (log-rank test P < 0.001). CONCLUSIONS: Clinical markers of
      liver dysfunction, recent mechanical ventilation, and renal impairment were
      independently associated with increased 1 year mortality. Presence of more than
      one clinical marker of organ dysfunction was associated with significantly
      increased risk of mortality in our study.

PMID- 22848077
TI  - High incidence of implantable cardioverter defibrillator malfunctions during
      radiation therapy: neutrons as a probable cause of soft errors.
AB  - AIMS: To investigate the behaviour of the implantable cardioverter defibrillator
      (ICD) function during actual radiotherapy sessions. METHODS AND RESULTS: Fifteen
      patients with an ICD underwent 17 radiation treatments for cancer [cumulative
      dose to the tumour was between 16 Gray (Gy) and 70 Gy; photon beams with maximum
      energies between 6 megaelectronvolt (MeV) and 18 MeV were employed]. During every
      session, the ICD was programmed to a monitoring mode to prevent inappropriate
      therapy delivery. Afterwards, the ICDs were interrogated to ensure proper
      function. Calculated radiation dose at the ICD site was <1 Gy in all patients. In
      5 out of 17 radiation treatments (29%) the ICDs showed 6 malfunctions (35%). We
      noticed four disturbances in the memory data or device resets during radiation
      treatment and one case of inappropriate ventricular fibrillation detection due to
      external noise. In one case a late device data error was observed. All
      malfunctions occurred at 10 and 18 MeV beam energies. CONCLUSION: Despite the
      fact that all recommended precautions were taken to minimize the damage to the
      ICDs during radiotherapy and the calculated dose to the ICDs was <1 Gy, in 29% of
      the treatments a malfunction occurred. We observed a possible correlation between
      the beam energy and the malfunctions. This correlation may be due to an
      interaction between neutrons produced in the head of the linear accelerator at
      beam energies >=10 MeV, and boron-10 which is present in the integrated circuit.

PMID- 22848078
TI  - Regulation of the sodium pump during cardiomyocyte adaptation to pregnancy.
AB  - Regulation of the sodium pump during normal pregnancy and its effect on the
      function of cardiomyocytes is poorly understood. Our objective was to evaluate
      the possible implication of the Na(+)-K(+)-ATPase, the sodium pump which controls
      cellular ionic and metabolic homeostasis, in the adaptations of cardiomyocytes to
      normal pregnancy. We have used Western blots and patch-clamp measurements to
      identify changes in the sodium pump proteins. Confocal microscopy was applied to
      estimate intracellular sodium concentration. Time-resolved spectroscopy was
      employed to measure mitochondrial NAD(P)H fluorescence and estimate oxidative
      metabolic state. Optical microscopy was adopted to study the contractility
      responses of cardiomyocytes. Cells from non-pregnant and pregnant rats (1 day
      prior parturition) were studied. Our results showed lower protein expression of
      the alpha1 Na(+)-K(+)-ATPase isoform in cardiomyocytes in pregnant rats,
      decreased sodium pump membrane current and elevated steady-state sodium
      concentration. In addition, ouabain, the inhibitor of the sodium pump capable of
      increasing cardiomyocyte contractility in non-pregnant rats in a concentration
      dependent manner, failed to affect cell contractions in pregnant rats. We also
      noted modified responsiveness of the mitochondrial metabolic state to ouabain in
      cardiac cells. The gathered data confirmed that in pregnant rats, the sodium pump
      protein content and transmembrane flux are decreased, while the sensitivity of
      cardiomyocyte contractility and the sensitivity of mitochondrial metabolic redox
      state to ouabain are modified, pointing to regulation of the Na(+)-K(+)-ATPase
      during cardiac cell adaptations to normal pregnancy.

PMID- 22848080
TI  - Sustained postexercise vasodilatation and histamine receptor activation following
      small muscle-mass exercise in humans.
AB  - A sustained postexercise vasodilatation, which is histamine receptor mediated,
      has been observed following single bouts of whole-body exercise, but the
      mechanisms that regulate activation of histamine receptors following exercise are
      undefined. Exploration of vasodilatation after small muscle-mass dynamic or
      resistance exercise could provide novel insight into the pathways responsible for
      histamine receptor activation. We hypothesized that there would be a
      vasodilatation of the previously exercised limb following small muscle-mass
      dynamic and resistance exercise, which would be mediated by histamine receptors.
      We studied men and women before and after single-leg dynamic (n = 9) or
      resistance knee-extension exercise (n = 12) on control and blockade days
      (combined oral H(1) and H(2) receptor antagonism with fexofenadine and
      ranitidine). We measured arterial blood pressure (automated brachial
      oscillometry) and femoral artery blood flow (Doppler ultrasound). Dynamic
      exercise elevated leg vascular conductance in the active leg by 27.2 +/- 8.4% at
      60 min postexercise (P < 0.05 versus pre-exercise), but did not alter conductance
      in the rested leg (change, 4.6 +/- 3.5%; P = 0.8 versus pre-exercise). The rise
      in conductance was abolished on the blockade day (change, 3.7 +/- 5.1%; P = 0.8
      versus pre-exercise, P = 0.2 versus control). Resistance exercise did not produce
      a sustained vasodilatation (change, -4.3 +/- 4.7% at 60 min postexercise; P = 0.7
      versus pre-exercise). These data indicate that histamine receptors are activated
      following dynamic, but not resistance, exercise. Furthermore, these data suggest
      that local factors associated with aerobic exercise, and not systemic factors or
      factors associated with high muscle force, are responsible for activation of
      histamine receptors in the previously exercised muscle.

PMID- 22848079
TI  - Nuclear factor-kappaB signalling and transcriptional regulation in skeletal
      muscle atrophy.
AB  - The nuclear factor-kappaB (NF-kappaB) signalling pathway is a necessary component
      of adult skeletal muscle atrophy resulting from systemic illnesses or disuse.
      Studies showing a role for the NF-kappaB pathway in muscle disuse include
      unloading, denervation and immobilization, and studies showing a role for NF
      kappaB in systemic illnesses include cancer, chronic heart failure and acute
      septic lung injury. Muscle atrophy due to most of these triggers is associated
      with activation of NF-kappaB transcriptional activity. With the exception of
      muscle unloading, however, there is a paucity of data on the NF-kappaB
      transcription factors that regulate muscle atrophy, and little is known about
      which genes are targeted by NF-kappaB transcription factors during atrophy.
      Interestingly, in some cases it appears that the amelioration of muscle atrophy
      by genetic inhibition of NF-kappaB signalling proteins is due to effects that are
      independent of the downstream NF-kappaB transcription factors. These questions
      are prime areas for investigation if we are to understand a key component of
      muscle wasting in adult skeletal muscle.

PMID- 22848081
TI  - Mechanism of macrophage migration inhibitory factor-induced decrease of T-type
      Ca(2+) channel current in atrium-derived cells.
AB  - The T-type Ca(2+) current (I(Ca,T)) plays an important role in the pathogenesis
      of atrial fibrillation (AF). The present study sought to investigate the role of
      macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, in the
      regulation of T-type Ca(2+) channels (TCCs) in atrial myocytes. We used the whole
      cell voltage-clamp technique and biochemical assays to study the regulation and
      expression of I(Ca,T) in atrial myocytes. Gene levels of the alpha1G and alpha1H
      subunit of TCCs were decreased in human atrial tissue of patients with AF. In
      cultured atrium-derived myocytes (HL-1 cells), mouse recombinant MIF (20 or 40
      nm, 24 h) suppressed peak I(Ca,T) in a concentration-dependent manner, impaired
      the voltage-dependent activation of I(Ca,T) and downregulated TCC alpha1G and
      alpha1H mRNA. The Src inhibitors genistein and PP1 significantly enhanced
      I(Ca,T). The reduction of I(Ca,T) and TCC subunit mRNA induced by recombinant MIF
      could be reversed by genistein and PP1. The TCC alpha1G associated with Src in HL
      1 cells and mouse cardiomycytes. Macrophage migration inhibitory factor is
      involved in the pathogenesis of AF, probably by decreasing the T-type calcium
      current in atrium-derived myocytes through impairment of channel function and
      activation of c-Src kinases, representing a potential pathogenic mechanism in
      atrial fibrillation.

PMID- 22848082
TI  - Cigarette smoke induces endoplasmic reticulum stress response and proteasomal
      dysfunction in human alveolar epithelial cells.
AB  - Cigarette smoking is the major risk factor for chronic obstructive pulmonary
      disease. Cigarette smoke (CS) causes oxidative stress and severe damage to
      proteins in the lungs. One of the main systems to protect cells from the
      accumulation of damaged proteins is the ubiquitin-proteasome pathway. In the
      present study, we aimed to find out whether exposure of alveolar epithelial cells
      to CS induces an endoplasmic reticulum (ER) stress response by accumulation of
      damaged proteins that are inefficiently degraded by the proteasomes. The
      hypothesis was tested in a human alveolar epithelial cell line (A549) exposed to
      gas-phase CS. Exposure to gas-phase CS for 5 min caused an increase in the amount
      of ubiquitin-protein conjugates within 4 h. Cigarette smoke exposure also induced
      the ER stress response marker eIF2alpha, followed by a significant reduction of
      nascent protein synthesis and increase in the level of free intracellular amino
      acids. Moreover, CS exposure significantly reduced all three proteasomal
      activities (caspase-, trypsin- and chymotrypsin-like activity) within 4 h, which
      was still present after 24 h. It can be concluded that gas-phase CS induces ER
      stress in A549 alveolar epithelial cells, leading to inadequate protein turnover
      caused by an accumulation of damaged proteins, reduction in nascent protein
      synthesis and inhibition of the proteasome. We suggest that prolonged ER stress
      may lead to excessive cell death with disruption of the epithelial barrier,
      contributing to development of chronic obstructive pulmonary disease.

PMID- 22848083
TI  - The Nlrp3 inflammasome promotes myocardial dysfunction in structural
      cardiomyopathy through interleukin-1beta.
AB  - Heart failure is associated with a low-grade and chronic cardiac inflammation
      that impairs function; however, the mechanisms by which this sterile inflammation
      occurs in structural heart disease remain poorly defined. Cardiac-specific
      heterozygous overexpression of the calcineurin transgene (CNTg) in mice results
      in cardiac hypertrophy, inflammation, apoptosis and ventricular dilatation. We
      hypothesized that activation of the Nlrp3 inflammasome, an intracellular danger
      sensing pathway required for processing the pro-inflammatory cytokine interleukin
      1beta (IL-1beta), may contribute to myocardial dysfunction and disease
      progression. Here we report that Nlrp3 mRNA was increased in CNTg mice compared
      with wild-type. Consistent with inflammasome activation, CNTg animals had
      increased conversion of pro-caspase-1 to cleaved and activated forms, as well as
      markedly increased serum IL-1beta. Blockade of IL-1beta signalling via chronic IL
      1 receptor antagonist therapy reduced cardiac inflammation and myocyte pathology
      in CNTg mice, resulting in improved systolic performance. Furthermore, genetic
      ablation of Nlrp3 in CNTg mice reduced pro-inflammatory cytokine maturation and
      cardiac inflammation, as well as improving systolic performance. These findings
      indicate that activation of the Nlrp3 inflammasome in CNTg mice promotes
      myocardial inflammation and systolic dysfunction through the production of pro
      inflammatory IL-1beta. Blockade of IL-1beta signalling with the IL-1 receptor
      antagonist reverses these phenotypes and offers a possible therapeutic approach
      in the management of heart failure.

PMID- 22848084
TI  - The wonders of the Wanderer.
AB  - Vagus is Latin for wandering, and the vagus nerve fully deserves this name due to
      its extensive distribution through the body. Indeed, one of the lines of the song
      that accompanied the 2012 G. L. Brown Prize Lecture exaggerates this diversity,
      'My function's almost anythin', and vagus is my name'. Alteration of vagal
      activity was first investigated in the 1880s as a treatment for epilepsy, and
      vagus nerve stimulation is now an approved treatment for refractory epilepsy and
      depression in the USA, despite an incomplete understanding of the mechanisms
      involved. Vagus nerve stimulation could be beneficial in many other conditions,
      including heart failure, tinnitus, chronic hiccups, Alzheimer's disease and
      inflammatory diseases. Inhibition of vagal activity could also be beneficial in
      some conditions, e.g. reducing activation of vagal respiratory afferents to treat
      chronic cough. This review discusses evidence underlying some current and
      potential therapeutic applications of vagal modulation, illustrating the wonders
      of the Wanderer.

PMID- 22848085
TI  - Contribution of blood viscosity in the assessment of flow-mediated dilation and
      arterial stiffness.
AB  - Flow-mediated dilation (FMD) is a non-invasive index of endothelial function. In
      an attempt to standardize FMD for shear stimulus, shear rate (velocity/diameter),
      rather than shear stress (viscosity*velocity/diameter), is commonly used as a
      surrogate measure, although it is limited by individual differences in blood
      viscosity. The purpose of this study was to determine the contribution of whole
      blood viscosity to FMD and other key measures of vascular function. Blood
      viscosity, FMD, carotid artery compliance, and carotid-femoral pulse wave
      velocity (cfPWV) were measured in 98 apparently healthy adults varying widely in
      age (18-63 years). Whole blood viscosity was not significantly correlated with
      FMD, cfPWV, or carotid artery compliance. Shear rate was a stronger correlate
      with FMD than shear stress that takes blood viscosity into account (r = 0.43 vs
      0.28). No significant differences were observed between whole blood viscosity and
      traditional risk factors for cardiovascular disease. Age was positively
      correlated with cfPWV (r = 0.65, p < 0.001) and negatively correlated with FMD (r
      = -0.24, p < 0.05) and carotid artery compliance (r = -0.45, p < 0.01).
      Controlling for viscosity did not reduce the strength of these relations. These
      results indicate that whole blood viscosity does not significantly impact
      measures of vascular function and suggests that the common practice to use shear
      rate, rather than shear stress, in the adjustment of FMD is valid.

PMID- 22848086
TI  - Peripheral pulmonary artery stenosis masquerading as pulmonary hypertension: a
      diagnostic and therapeutic challenge.
AB  - Isolated peripheral pulmonary artery stenosis presenting in adulthood is an
      uncommon cause of right ventricular hypertension and may be misdiagnosed as
      primary or thromboembolic pulmonary hypertension. Treatment consists of balloon
      angioplasty and stenting of the affected vessels, although the procedure can be
      complicated by reperfusion pulmonary edema.

PMID- 22848089
TI  - The diversification of terpene emissions in Mediterranean oaks: lessons from a
      study of Quercus suber, Quercus canariensis and its hybrid Quercus afares.
AB  - Interspecific gene flow is common in oaks. In the Mediterranean, this process
      produced geographical differentiations and new species, which may have
      contributed to the diversification of the production of volatile terpenes in the
      oak species of this region. The endemic North African deciduous oak Quercus
      afares (Pomel) is considered to be a stabilized hybrid between the evergreen
      Quercus suber (L.) and the deciduous Quercus canariensis (Willd.), presumably
      being monoterpene and isoprene emitters, respectively. In a common garden
      experiment, we examined the terpene emission capacities, terpene synthase (TPS)
      activities and nuclear genetic markers in 52 trees of these three oak species.
      All but one of the Q. suber and Q. canariensis trees were found to be genetically
      pure, whereas most Q. afares trees possessed a mixed genotype with a predominance
      of Q. suber alleles. Analysis of the foliar terpene emissions and TPS activities
      revealed that all the Q. canariensis trees strongly produced isoprene while all
      the Q. suber trees were strong monoterpene producers. Quercus afares trees
      produced monoterpenes as well but at more variable and significantly lower rates,
      and with a monoterpene pattern different than that observed in Q. suber. Among 17
      individuals tested, one Q. afares tree emitted only an insignificant amount of
      terpenes. No mixed isoprene/monoterpene emitter was detected. Our results suggest
      that the capacity and pattern of volatile terpene production in Algerian Q.
      afares populations have strongly diverged from those of its parental species and
      became quantitatively and qualitatively reduced, including the complete
      suppression of isoprene production.

PMID- 22848090
TI  - Chlorophyll alpha fluorescence analysis along a vertical gradient of the crown in
      a poplar (Oxford clone) subjected to ozone and water stress.
AB  - An experiment in open-top chambers was carried out in summer 2008 at Curno
      (Northern Italy) in order to study the effects of ozone and mild water stress on
      poplar cuttings (Oxford clone). In this experiment direct fluorescence parameters
      (JIP-test) were measured in leaves from different sections of the crown (L:
      lower; M: medium; U: upper parts of the crown). The parameters considered were
      calculated at the different steps of the fluorescence transient, and include
      maximum quantum yield efficiency in the dark-adapted state (F(v)/F(M)); the L
      band, at 100 ? s, that expresses the stability of the tripartite system reaction
      centre-harvesting light complex-core antenna; the K-band, at 300 ? s, that
      expresses the efficiency of the oxygen-evolving complex; the J-phase, at 2 ms,
      that expresses the efficiency with which a trapped exciton can move an electron
      into the electron transport chain from Q(A)(-) to the intersystem electron
      acceptors; the IP-phase, which expresses the efficiency of electron transport
      around the photosystem 1 (PSI) to reduce the final acceptors of the electron
      transport chain, i.e., ferredoxin and NADP; and finally the performance index
      total (PItot) for energy conservation from photons absorbed by PSII to the
      reduction flux of PSI end acceptors. The main results are: (i) different dynamics
      were observed between leaves in the lower section, whose PItot decreased over
      time, and those in the upper sections in which it increased, with a dynamic
      connected to the leaf age; (ii) ozone depressed all the considered fluorescence
      parameters in basal leaves of well-watered plants, while it had little or no
      damaging effect on medium-level or upper-section leaves; (iii) PItot and IP-phase
      increased in upper leaves of plants subjected to ozone stress, as well as the net
      photosynthesis; (iv) water stress increased PItot of leaves in all levels of the
      crown. The results suggest that ozone-damaged poplar plants compensate, at least
      partially, for the loss of photosynthesis with higher photosynthetic rates in
      young leaves (in the upper section of the crown), more efficient to fix carbon.

PMID- 22848088
TI  - An extreme case of plant-insect codiversification: figs and fig-pollinating
      wasps.
AB  - It is thought that speciation in phytophagous insects is often due to
      colonization of novel host plants, because radiations of plant and insect
      lineages are typically asynchronous. Recent phylogenetic comparisons have
      supported this model of diversification for both insect herbivores and
      specialized pollinators. An exceptional case where contemporaneous plant-insect
      diversification might be expected is the obligate mutualism between fig trees
      (Ficus species, Moraceae) and their pollinating wasps (Agaonidae, Hymenoptera).
      The ubiquity and ecological significance of this mutualism in tropical and
      subtropical ecosystems has long intrigued biologists, but the systematic
      challenge posed by >750 interacting species pairs has hindered progress toward
      understanding its evolutionary history. In particular, taxon sampling and
      analytical tools have been insufficient for large-scale cophylogenetic analyses.
      Here, we sampled nearly 200 interacting pairs of fig and wasp species from across
      the globe. Two supermatrices were assembled: on an average, wasps had sequences
      from 77% of 6 genes (5.6 kb), figs had sequences from 60% of 5 genes (5.5 kb),
      and overall 850 new DNA sequences were generated for this study. We also
      developed a new analytical tool, Jane 2, for event-based phylogenetic
      reconciliation analysis of very large data sets. Separate Bayesian phylogenetic
      analyses for figs and fig wasps under relaxed molecular clock assumptions
      indicate Cretaceous diversification of crown groups and contemporaneous
      divergence for nearly half of all fig and pollinator lineages. Event-based
      cophylogenetic analyses further support the codiversification hypothesis.
      Biogeographic analyses indicate that the present-day distribution of fig and
      pollinator lineages is consistent with a Eurasian origin and subsequent
      dispersal, rather than with Gondwanan vicariance. Overall, our findings indicate
      that the fig-pollinator mutualism represents an extreme case among plant-insect
      interactions of coordinated dispersal and long-term codiversification.
      [Biogeography; coevolution; cospeciation; host switching; long-branch attraction;
      phylogeny.].

PMID- 22848091
TI  - PKCdelta regulates death receptor 5 expression induced by PS-341 through ATF4
      ATF3/CHOP axis in human lung cancer cells.
AB  - PS-341 (bortezomib), a proteasome inhibitor, has been approved for the treatment
      of multiple myeloma. Our previous work has shown that PS-341 induces death
      receptor 5 (DR5)-dependent apoptosis and enhances the TNF-related apoptosis
      inducing ligand-induced apoptosis in human non-small cell lung cancer cells.
      However, the definite mechanism remains undefined. In the present study, we
      reveal that PKCdelta and RSK2 mediate PS-341-induced DR5 upregulation, involving
      coactivation of endoplasmic reticulum (ER) stress. We discovered that PS-341
      activated ER stress through elevating the expression of BiP, p-eIF2alpha,
      IRE1alpha, ATF4, ATF3, and CCAAT/enhancer-binding protein homologous protein
      (CHOP). Further study showed that DR5 upregulation was dependent on ATF4, ATF3,
      and CHOP expression. Silencing either one of the ATF4, ATF3, and CHOP expression
      decreased DR5 upregulation and subsequent apoptosis. We determined that ATF4
      regulated ATF3 and CHOP expression. Thereafter, ATF3 and CHOP formed a complex
      and regulated DR5 expression. In addition, we discovered that the phosphorylation
      of extracellular signal-regulated kinase (ERK) 1/2 and RSK2 were elevated after
      PS-341 treatment and inhibition of their phosphorylation using MAP-ERK kinase 1/2
      inhibitor decreased the DR5 level, indicating that ERK/RSK2 signaling is involved
      in DR5 upregulation. Furthermore, we detected the cleavage of PKCdelta, and the
      blockage of PKCdelta expression cut down DR5 upregulation and apoptosis.
      Importantly, knockdown of PKCdelta expression decreased the induction of ER
      stress and the phosphorylation of ERK1/2 and RSK2, suggesting that PKCdelta
      regulates DR5 expression through ERK/RSK2 signaling and ATF4-CHOP/ATF3 axis.
      Collectively, we show that PS-341 induces PKCdelta-dependent DR5 expression
      through activation of ERK/RSK2 and ER stress signaling pathway.

PMID- 22848092
TI  - REST is a novel prognostic factor and therapeutic target for medulloblastoma.
AB  - Medulloblastoma is a malignant pediatric brain tumor. Current treatment following
      patient stratification into standard and high-risk groups using clinical features
      has improved survival. However, a subset of patients with standard risk features
      have unanticipated aggressive disease, underscoring the need for a better
      understanding of tumor biology and the development of novel treatments. Poor
      differentiation, a hallmark of medulloblastomas is associated with elevated
      expression levels of the repressor of neuronal differentiation called repressor
      element 1-silencing transcription factor (REST). Here, we assessed whether
      elevated REST expression levels had prognostic significance and whether its
      pharmacologic manipulation would promote neurogenesis and block tumor cell
      growth. REST levels in patient tumors were measured by immunohistochemistry and
      stratified into negative, low/moderate- (+/++/+++), and high-REST (+++++) groups.
      Kaplan-Meier curves revealed that patients with high-REST tumors had worse
      overall and event-free survival compared with patients with REST-negative or REST
      low tumors. Because histone deacetylases (HDAC) are required for REST-dependent
      repression of neurogenesis, we evaluated a panel of HDAC inhibitors (HDACI) for
      their effects on growth and differentiation of established and primary REST
      positive cell lines. MS-275, trichostatin-A (TSA), valproic acid (VPA), and
      suberoylanilide hydroxamic acid (SAHA) upregulated expression of the REST-target
      neuronal differentiation gene, Syn1, suggesting a potential effect of these
      HDACIs on REST function. Interestingly, VPA and TSA substantially increased
      histone acetylation at the REST promoter and activated its transcription, whereas
      SAHA unexpectedly promoted its proteasomal degradation. A REST-dependent decrease
      in cell growth was also observed following SAHA treatment. Thus, our studies
      suggest that HDACIs may have therapeutic potential for patients with REST
      positive tumors. This warrants further investigation.

PMID- 22848093
TI  - Targeting subcellular localization through the polo-box domain: non-ATP
      competitive inhibitors recapitulate a PLK1 phenotype.
AB  - The polo-box domain (PBD) has critical roles in the mitotic functions of polo
      like kinase 1 (PLK1). The replacement with partial ligand alternative through
      computational enrichment (REPLACE) strategy to develop inhibitors of protein
      protein interactions has identified alternatives for the N-terminal tripeptide of
      a Cdc25C substrate. In addition, a peptide structure-activity relationship
      described key determinants and novel information useful for drug design. Fragment
      ligated inhibitory peptides (FLIP) were generated with comparable affinity to
      peptide PBD inhibitors and possessed antiproliferative phenotypes in cells
      consistent with the observed decrease in PLK1 centrosomal localization. These
      FLIPs showed evidence of enhanced PLK1 inhibition in cells relative to peptides
      and induced monopolar and multipolar spindles, which stands in contrast to
      previously reported small-molecule PBD inhibitors that display phenotypes only
      partially representative of PLK1 knockdown. Progress obtained applying REPLACE
      validates this approach for identifying fragment alternatives for determinants of
      the Cdc25C-binding motif and extends its applicability of the strategy for
      discovering protein-protein interaction inhibitors. In addition, the described
      PBD inhibitors retain high specificity for PLK1 over PLK3 and therefore show
      promise as isotype selective, non-ATP competitive kinase inhibitors that provide
      new impetus for the development of PLK1-selective antitumor therapeutics.

PMID- 22848095
TI  - Endocytic trafficking towards the vacuole plays a key role in the auxin receptor
      SCF(TIR)-independent mechanism of lateral root formation in A. thaliana.
AB  - Plants' developmental plasticity plays a pivotal role in responding to
      environmental conditions. One of the most plastic plant organs is the root
      system. Different environmental stimuli such as nutrients and water deficiency
      may induce lateral root formation to compensate for a low level of water and/or
      nutrients. It has been shown that the hormone auxin tunes lateral root
      development and components for its signaling pathway have been identified. Using
      chemical biology, we discovered an Arabidopsis thaliana lateral root formation
      mechanism that is independent of the auxin receptor SCF(TIR). The bioactive
      compound Sortin2 increased lateral root occurrence by acting upstream from the
      morphological marker of lateral root primordium formation, the mitotic activity.
      The compound did not display auxin activity. At the cellular level, Sortin2
      accelerated endosomal trafficking, resulting in increased trafficking of plasma
      membrane recycling proteins to the vacuole. Sortin2 affected Late
      endosome/PVC/MVB trafficking and morphology. Combining Sortin2 with well-known
      drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is
      pivotal for Sortin2-induced SCF(TIR)-independent lateral root initiation. Our
      results revealed a distinctive role for endosomal trafficking in the promotion of
      lateral root formation via a process that does not rely on the auxin receptor
      complex SCF(TIR).

PMID- 22848096
TI  - Reductions in artemisinin-based combination therapy consumption after the
      nationwide scale up of routine malaria rapid diagnostic testing in Zambia.
AB  - The National Malaria Control Center of Zambia introduced rapid diagnostic tests
      (RDTs) to detect Plasmodium falciparum as a pilot in some districts in 2005 and
      2006; scale up at a national level was achieved in 2009. Data on RDT use, drug
      consumption, and diagnostic results were collected in three Zambian health
      districts to determine the impact RDTs had on malaria case management over the
      period 2004-2009. Reductions were seen in malaria diagnosis and antimalarial drug
      prescription (66.1 treatments per facility-month (95% confidence interval [CI] =
      44.7-87.4) versus 26.6 treatments per facility-month (95% CI = 11.8-41.4)) pre-
      and post-RDT introduction. Results varied between districts, with significant
      reductions in low transmission areas but none in high areas. Rapid diagnostic
      tests may contribute to rationalization of treatment of febrile illness and
      reduce antimalarial drug consumption in Africa; however, their impact may be
      greater in lower transmission areas. National scale data will be necessary to
      confirm these findings.

PMID- 22848094
TI  - Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade,
      for the treatment of malignant peripheral nerve sheath tumors.
AB  - There is a critical need for efficacious therapeutic strategies to improve the
      outcome of patients afflicted by malignant peripheral nerve sheath tumors
      (MPNST). Multiple lines of evidence suggest a role for deregulated
      phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an
      attractive target for therapeutic manipulation. On the basis of previous
      observations obtained from in vitro experimentation, here we aimed to assess the
      effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of
      XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer
      clinical trials, was tested in two human MPNST xenograft models (STS26T and
      MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765
      abrogated human MPNST local and metastatic growth in severe combined
      immunodeficient mice. Notably, this therapeutic approach failed to induce
      apoptosis in MPNST cells but rather resulted in marked productive autophagy.
      Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic
      resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell
      death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic
      regimen of MPNST xenografts after pretreatment with XL765 resulted in superior
      antitumor effects as compared with either agent alone. Together, preclinical
      studies described here expand our previous findings and suggest that PI3K/mTOR
      inhibition alone and (most importantly) in combination with autophagy blockade
      may comprise a novel and efficacious therapy for patients harboring MPNST.

PMID- 22848098
TI  - Validation of the efficacy of a solar-thermal powered autoclave system for off
      grid medical instrument wet sterilization.
AB  - This work describes the efficacy of a solar-thermal powered autoclave used for
      the wet sterilization of medical instruments in off-grid settings where
      electrical power is not readily available. Twenty-seven trials of the solar
      thermal powered system were run using an unmodified non-electric autoclave loaded
      with a simulated bundle of medical instruments and biological test agents.
      Results showed that in 100% of the trials the autoclave achieved temperatures in
      excess of 121 degrees C for 30 minutes, indicator tape displayed visible
      reactions to steam sterilization, and biological tests showed that microbial
      agents had been eliminated, in compliance with the Centers for Disease Control
      and Prevention requirements for efficacious wet sterilization.

PMID- 22848097
TI  - Etiology of anemia among infants, school-aged children, and young non-pregnant
      women in different settings of South-Central Cote d'Ivoire.
AB  - Anemia affects one-quarter of the world's population, but its etiology remains
      poorly understood. We determined the prevalence of anemia and studied underlying
      risk factors in infants (6-23 months), young school-aged children (6-8 years),
      and young non-pregnant women (15-25 years) in south-central Cote d'Ivoire. Blood,
      stool, and urine samples were subjected to standardized, quality-controlled
      methods. We found high prevalence of anemia, malaria, inflammation, and
      deficiencies of iron, riboflavin, and vitamin A but low prevalence and
      intensities of soil-transmitted helminth and schistosome infections. Multivariate
      regression analysis revealed significant associations between anemia and
      Plasmodium falciparum for infants, inflammation for school-aged children, and
      cellular iron deficiency for both school-aged children and non-pregnant women.
      Women with riboflavin deficiency had significantly lower odds of anemia. Our
      findings call for interventions to protect infants from malaria, improved intake
      of dietary iron, better access to health care, and health education.

PMID- 22848099
TI  - Human antibody response to Aedes aegypti saliva in an urban population in
      Bolivia: a new biomarker of exposure to Dengue vector bites.
AB  - Aedes mosquitoes are important vectors of re-emerging diseases in developing
      countries, and increasing exposure to Aedes in the developed world is currently a
      source of concern. Given the limitations of current entomologic methods, there is
      a need for a new effective way for evaluating Aedes exposure. Our objective was
      to evaluate specific antibody responses to Aedes aegypti saliva as a biomarker
      for vector exposure in a dengue-endemic urban area. IgG responses to saliva were
      strong in young children and steadily waned with age. Specific IgG levels were
      significantly higher in persons living in sites with higher Ae. aegypti density,
      as measured by using entomologic parameters. Logistic regression showed a
      significant correlation between IgG to saliva and exposure level, independently
      of either age or sex. These results suggest that antibody responses to saliva
      could be used to monitor human exposure to Aedes bites.

PMID- 22848100
TI  - Genetic variation of CTNNB1 gene is associated with susceptibility and prognosis
      of gastric cancer in a Chinese population.
AB  - Gastric cancer is the second leading cause of cancer-related death worldwide with
      a low 5-year survival (S5y) after initial diagnosis. Although aberrant Wnt/beta
      catenin (CTNNB1) signaling has been observed in multiple human cancers, there is
      no information on the role of CTNNB1 polymorphisms in gastric cancer risk and
      S5y. We performed a genetic association study to analyse the correlation between
      the five tagged SNPs (tSNPs) (rs4135385, rs1798808, rs1880481, rs11564465 and
      rs2293303) of CTNNB1 and gastric cancer risk and survival. A total of 944
      patients with complete follow-up information and 848 cancer-free controls were
      enrolled in this study. The rs1880481 polymorphism was correlated with decreased
      risk of gastric cancer [AC/AA vs. CC: adjusted odds ratio (OR) = 0.76, 95%
      confidence interval (CI) = 0.63-0.91], whereas the three other SNPs showed
      opposite effect (AG/AA vs. GG: adjusted OR = 1.31, 95% CI = 1.08-1.57 for
      rs4135385; GG vs. AA/AG: 2.09, 1.02-4.28 for rs11564475; TT vs. CC/CT: 4.87, 2.72
      8.71 for rs2293303). We further investigated if these tSNPs were related to the
      S5y of gastric cancer, and the results displayed that only the SNP rs4135385
      AG/AA genotypes were significantly associated with a favorable gastric cancer
      survival compared with the GG genotype [adjusted hazard ratio (HR) = 0.80, 95% CI
      = 0.66-0.97], and the association was more prominent among patients with non
      cardia gastric cancer (NCGC) than those with cardia gastric cancer (CGC) (Log
      rank P = 0.007 for NCGC and 0.417 for CGC). Our results indicated that the
      genetic variants of CTNNB1 could be used as predictors of gastric cancer
      susceptibility and prognosis.

PMID- 22848101
TI  - A distant cis acting intronic element induces site-selective RNA editing.
AB  - Transcripts have been found to be site selectively edited from adenosine-to
      inosine (A-to-I) in the mammalian brain, mostly in genes involved in
      neurotransmission. While A-to-I editing occurs at double-stranded structures,
      other structural requirements are largely unknown. We have investigated the
      requirements for editing at the I/M site in the Gabra-3 transcript of the GABA(A)
      receptor. We identify an evolutionarily conserved intronic duplex, 150 nt
      downstream of the exonic hairpin where the I/M site resides, which is required
      for its editing. This is the first time a distant RNA structure has been shown to
      be important for A-to-I editing. We demonstrate that the element also can induce
      editing in related but normally not edited RNA sequences. In human, thousands of
      genes are edited in duplexes formed by inverted repeats in non-coding regions. It
      is likely that numerous such duplexes can induce editing of coding regions
      throughout the transcriptome.

PMID- 22848102
TI  - Structural and functional analyses of the interaction of archaeal RNA polymerase
      with DNA.
AB  - Multi-subunit RNA polymerases (RNAPs) in all three domains of life share a common
      ancestry. The composition of the archaeal RNAP (aRNAP) is not identical between
      phyla and species, with subunits Rpo8 and Rpo13 found in restricted subsets of
      archaea. While Rpo8 has an ortholog, Rpb8, in the nuclear eukaryal RNAPs, Rpo13
      lacks clear eukaryal orthologs. Here, we report crystal structures of the DNA
      bound and free form of the aRNAP from Sulfolobus shibatae. Together with
      biochemical and biophysical analyses, these data show that Rpo13 C-terminus binds
      non-specifically to double-stranded DNA. These interactions map on our RNAP-DNA
      binary complex on the downstream DNA at the far end of the DNA entry channel. Our
      findings thus support Rpo13 as a RNAP-DNA stabilization factor, a role
      reminiscent of eukaryotic general transcriptional factors. The data further yield
      insight into the mechanisms and evolution of RNAP-DNA interaction.

PMID- 22848104
TI  - A small RNA response at DNA ends in Drosophila.
AB  - Small RNAs have been implicated in numerous cellular processes, including effects
      on chromatin structure and the repression of transposons. We describe the
      generation of a small RNA response at DNA ends in Drosophila that is analogous to
      the recently reported double-strand break (DSB)-induced RNAs or Dicer- and Drosha
      dependent small RNAs in Arabidopsis and vertebrates. Active transcription in the
      vicinity of the break amplifies this small RNA response, demonstrating that the
      normal messenger RNA contributes to the endogenous small interfering RNAs
      precursor. The double-stranded RNA precursor forms with an antisense transcript
      that initiates at the DNA break. Breaks are thus sites of transcription
      initiation, a novel aspect of the cellular DSB response. This response is
      specific to a double-strand break since nicked DNA structures do not trigger
      small RNA production. The small RNAs are generated independently of the exact end
      structure (blunt, 3'- or 5'-overhang), can repress homologous sequences in trans
      and may therefore--in addition to putative roles in repair--exert a quality
      control function by clearing potentially truncated messages from genes in the
      vicinity of the break.

PMID- 22848105
TI  - Benchmarking spliced alignment programs including Spaln2, an extended version of
      Spaln that incorporates additional species-specific features.
AB  - Spliced alignment plays a central role in the precise identification of
      eukaryotic gene structures. Even though many spliced alignment programs have been
      developed, recent rapid progress in DNA sequencing technologies demands further
      improvements in software tools. Benchmarking algorithms under various conditions
      is an indispensable task for the development of better software; however, there
      is a dire lack of appropriate datasets usable for benchmarking spliced alignment
      programs. In this study, we have constructed two types of datasets: simulated
      sequence datasets and actual cross-species datasets. The datasets are designed to
      correspond to various real situations, i.e. divergent eukaryotic species,
      different types of reference sequences, and the wide divergence between query and
      target sequences. In addition, we have developed an extended version of our
      program Spaln, which incorporates two additional features to the scoring scheme
      of the original version, and examined this extended version, Spaln2, together
      with the original Spaln and other representative aligners based on our benchmark
      datasets. Although the effects of the modifications are not individually
      striking, Spaln2 is consistently most accurate and reasonably fast in most
      practical cases, especially for plants and fungi and for increasingly divergent
      pairs of target and query sequences.

PMID- 22848103
TI  - DNA of a circular minichromosome linearized by restriction enzymes or other
      reagents is resistant to further cleavage: an influence of chromatin topology on
      the accessibility of DNA.
AB  - The accessibility of DNA in chromatin is an essential factor in regulating its
      activities. We studied the accessibility of the DNA in a ~170 kb circular
      minichromosome to DNA-cleaving reagents using pulsed-field gel electrophoresis
      and fibre-fluorescence in situ hybridization on combed DNA molecules. Only one of
      several potential sites in the minichromosome DNA was accessible to restriction
      enzymes in permeabilized cells, and in growing cells only a single site at an
      essentially random position was cut by poisoned topoisomerase II,
      neocarzinostatin and gamma-radiation, which have multiple potential cleavage
      sites; further sites were then inaccessible in the linearized minichromosomes.
      Sequential exposure to combinations of these reagents also resulted in cleavage
      at only a single site. Minichromosome DNA containing single-strand breaks created
      by a nicking endonuclease to relax any unconstrained superhelicity was also cut
      at only a single position by a restriction enzyme. Further sites became
      accessible after >=95% of histones H2A, H2B and H1, and most non-histone proteins
      were extracted. These observations suggest that a global rearrangement of the
      three-dimensional packing and interactions of nucleosomes occurs when a circular
      minichromosome is linearized and results in its DNA becoming inaccessible to
      probes.

PMID- 22848106
TI  - Biochemical and structural characterization of the glycosylase domain of MBD4
      bound to thymine and 5-hydroxymethyuracil-containing DNA.
AB  - Active DNA demethylation in mammals occurs via hydroxylation of 5-methylcytosine
      to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family of
      proteins (TETs). 5hmC residues in DNA can be further oxidized by TETs to 5
      carboxylcytosines and/or deaminated by the Activation Induced
      Deaminase/Apolipoprotein B mRNA-editing enzyme complex family proteins to 5
      hydromethyluracil (5hmU). Excision and replacement of these intermediates is
      initiated by DNA glycosylases such as thymine-DNA glycosylase (TDG), methyl
      binding domain protein 4 (MBD4) and single-strand specific monofunctional uracil
      DNA glycosylase 1 in the base excision repair pathway. Here, we report detailed
      biochemical and structural characterization of human MBD4 which contains mismatch
      specific TDG activity. Full-length as well as catalytic domain (residues 426-580)
      of human MBD4 (MBD4(cat)) can remove 5hmU when opposite to G with good
      efficiency. Here, we also report six crystal structures of human MBD4(cat): an
      unliganded form and five binary complexes with duplex DNA containing a T*G,
      5hmU*G or AP*G (apurinic/apyrimidinic) mismatch at the target base pair. These
      structures reveal that MBD4(cat) uses a base flipping mechanism to specifically
      recognize thymine and 5hmU. The recognition mechanism of flipped-out 5hmU bases
      in MBD4(cat) active site supports the potential role of MBD4, together with TDG,
      in maintenance of genome stability and active DNA demethylation in mammals.

PMID- 22848107
TI  - Structure and cleavage activity of the tetrameric MspJI DNA modification
      dependent restriction endonuclease.
AB  - The MspJI modification-dependent restriction endonuclease recognizes 5
      methylcytosine or 5-hydroxymethylcytosine in the context of CNN(G/A) and cleaves
      both strands at fixed distances (N(12)/N(16)) away from the modified cytosine at
      the 3'-side. We determined the crystal structure of MspJI of Mycobacterium sp.
      JLS at 2.05-A resolution. Each protein monomer harbors two domains: an N-terminal
      DNA-binding domain and a C-terminal endonuclease. The N-terminal domain is
      structurally similar to that of the eukaryotic SET and RING-associated domain,
      which is known to bind to a hemi-methylated CpG dinucleotide. Four protein
      monomers are found in the crystallographic asymmetric unit. Analytical gel
      filtration and ultracentrifugation measurements confirm that the protein exists
      as a tetramer in solution. Two monomers form a back-to-back dimer mediated by
      their C-terminal endonuclease domains. Two back-to-back dimers interact to
      generate a tetramer with two double-stranded DNA cleavage modules. Each cleavage
      module contains two active sites facing each other, enabling double-strand DNA
      cuts. Biochemical, mutagenesis and structural characterization suggest three
      different monomers of the tetramer may be involved respectively in binding the
      modified cytosine, making the first proximal N(12) cleavage in the same strand
      and then the second distal N(16) cleavage in the opposite strand. Both cleavage
      events require binding of at least a second recognition site either in cis or in
      trans.

PMID- 22848109
TI  - Intradialytic hypotension: a case for going slow and looking carefully.

PMID- 22848108
TI  - Silencing of Parkinson's disease-associated genes with artificial mirtron mimics
      of miR-1224.
AB  - Mirtrons are a recently described category of microRNA (miRNA) relying on
      splicing rather than processing by the microprocessor complex to generate pre
      miRNA precursors of the RNA interference (RNAi) pathway. Their discovery and
      subsequent verification provides important information about a distinct class of
      miRNA and inherent advantages that could be exploited to silence genes of
      interest. These include micro-processor-independent biogenesis, pol-II-dependent
      transcription, accurate species generation and the delivery of multiple
      artificial mirtrons as introns within a single host transcript. Here we
      determined the sequence motifs required for correct processing of the mmu-miR
      1224 mirtron and incorporated these into artificial mirtrons targeting
      Parkinson's disease-associated LRRK2 and alpha-synuclein genes. By incorporating
      these rules associated with processing and splicing, artificial mirtrons could be
      designed and made to silence complementary targets either at the mRNA or protein
      level. We further demonstrate with a LRRK2 targeting artificial mirtron that
      neuronal-specific silencing can be directed under the control of the human
      synapsin promoter. Finally, multiple mirtrons were co-delivered within a single
      host transcript, an eGFP reporter, to allow simultaneous targeting of two or more
      targets in a combinatorial approach. Thus, the unique characteristics of
      artificial mirtrons make this an attractive approach for future RNAi
      applications.

PMID- 22848110
TI  - FGF-23 in children with CKD: a new player in the development of CKD-mineral and
      bone disorder.
AB  - Disturbances in mineral and bone metabolism in children with chronic kidney
      disease (CKD) lead to specific abnormalities of skeletal homeostasis called CKD
      mineral and bone disorder (CKD-MBD). These disturbances should be diagnosed and
      managed appropriately to prevent bone deformities and disturbed growth. Changes
      in the vitamin D and parathyroid hormone (PTH), and the subsequent alterations in
      calcium (Ca) and phosphate (P) homeostasis are considered responsible for the
      development of CKD-MBD. Recently, a phosphaturic hormone, the fibroblast growth
      factor-23 (FGF-23), has been reported as a key regulator of P and vitamin D
      metabolism. A number of recent studies in paediatric populations have documented
      that the FGF-23 levels are increased early in CKD, before any abnormalities in
      serum Ca, P or PTH are apparent. The elevated FGF-23 levels result in a negative
      P balance to maintain P homeostasis, inducing phosphaturia, independently of PTH,
      and suppressing vitamin D synthesis. Therefore, the bone-kidney-parathyroid
      endocrine axis mediated by FGF-23 should be a novel therapeutic target in
      clinical practice, even in early stages of CKD in children.

PMID- 22848111
TI  - Are amblyopia treatments really all equal? Is that even the right question?
AB  - A series of Pediatric Eye Disease Investigator Group amblyopia treatment studies
      have concluded that the difference between patching and atropine penalization is
      inconsequential, and that there is no statistically significant difference
      between various amounts of prescribed patching. These results, representing mean
      behavior of groups of amblyopia patients, suggest that a broader range of initial
      treatments are appropriate than many previously believed; however, it is less
      clear how this informs treatment in individual cases.

PMID- 22848112
TI  - Medial rectus surgery for convergence excess esotropia with an accommodative
      component: a comparison of augmented recession, slanted recession, and recession
      with posterior fixation.
AB  - Richard G. Scobee was an internationally renowned strabismologist whose life was
      short yet very productive. The first section of this paper describes his life and
      contributions to strabismology and orthoptics. The second section of this paper
      reports the results of our strabismological study. INTRODUCTION AND PURPOSE: Many
      different surgical procedures exist for the treatment of children or adults with
      convergence excess esotropia. We report on our results of augmented recession,
      slanted recession, and recession with posterior fixation of the medial rectus
      muscle in such situations. We also report on the incidence of induced vertical
      deviations. METHODS: Using a retrospective chart review of 800 patients, we
      excluded patients with confounding strabismus conditions and pharmacological
      treatments leaving 131 patients included in the study. Slanted reinsertion of
      medial rectus (twenty-seven patients); posterior fixation with recession of
      medial rectus (twenty-two patients); augmented medial rectus recession (fifty
      eight patients); nonaugmented recession of medial rectus (seventy-three
      patients). The distance near disparity postoperatively was evaluated using a life
      table analysis in which all patients were grouped according to the length of time
      postoperatively. Induced vertical deviation was evaluated at least 6 months
      postoperatively. RESULTS: At all time periods postoperatively, the patients with
      slanted recessions showed the greatest reduction in distance near disparity and
      that reduction was the most stable over time. At 12- 14 months postoperatively,
      the range in reduction measured 7.9- 11(Delta) among all three procedures. At 15-
      18 months postoperatively, the range in reduction measured 16.9- 19.3(Delta)
      diopters among the three procedures. At greater than 6 months postoperatively,
      the slanted and augmented recession groups showed up to 1(Delta) of right
      hypertropia and the posterior fixation and nonaugmented groups showed up to
      0.6(Delta) of left hypertropia. CONCLUSIONS: All three medial rectus procedures
      used in our retrospective study (slanted recession, augmented recession,
      recession with posterior fixation) reduced the distance near disparity. The
      greatest and most stable reduction at all time periods postoperatively occurred
      with the slanted recession. The induced vertical deviation is small in all
      procedures and is acceptable at 1(Delta) or less. The augmented and slanted
      recessions are easier to perform than the posterior fixation with recession. We
      recommend that the slanted reinsertion of the medial rectus recession be
      considered as a viable option in the surgical correction of esotropia with a
      distance near disparity.

PMID- 22848113
TI  - Where the wild things are: when esotropia misbehaves.
AB  - Esotropia is the most common form of strabismus seen in clinic. Accommodation is
      known to be an important precipitating factor, and its management is usually not
      complex. In this paper, I have reviewed a dozen circumstances in which the
      presentation was complicated. For some patients, the cause of fleeting symptoms
      was elusive and had to be determined through careful sensory and motor testing.
      In others, the presentation was indicative of serious underlying pathology that
      warranted further investigation. Lastly, restrictive conditions may be
      erroneously thought to be neurological, and some of these are also discussed. The
      patients presented include the following problems: fixation switch diplopia,
      consecutive esotropia unmasking superior oblique palsy, over-corrected myopia,
      acute nonaccommodative esotropia, comitant esotropia with underlying cerebellar
      tumor, sixth nerve palsy due to pontine tumor or cavernous pathology, and thyroid
      strabismus mimicking sixth nerve palsy.

PMID- 22848114
TI  - Positive angle kappa: a possible sign of aniridia.
AB  - INTRODUCTION AND PURPOSE: Aniridia is a panocular disorder with variable
      expressivity, caused by PAX6 mutations. Foveal hypoplasia and nystagmus occur in
      both aniridia and albinism. Individuals with albinism have a moderately positive
      angle kappa. This study evaluates the angle kappa in individuals with aniridia.
      PATIENTS AND METHOD: We performed a retrospective chart review of recorded angle
      kappa for individuals with aniridia. In addition, we prospectively examined the
      monocular corneal light reflex in each eye of patients with congenital aniridia
      and central fixation. We recorded other ocular characteristics and the results of
      gene testing. Patients with eccentric fixation or corneal surgery were excluded,
      as were patients with retinal abnormalities that might have influenced the angle
      kappa. RESULTS: We included sixteen individuals with congenital aniridia and
      found that all had a positive angle kappa. Two patients underwent pattern visual
      evoked potential (VEP) testing with monocular stimulation and were found to have
      a reversal of polarity, indicating misrouting of the retino-striate fibers.
      CONCLUSION: The phenotype of aniridia is variable. However, a positive angle
      kappa may be considered to be a frequent clinical feature of aniridia.

PMID- 22848115
TI  - A new method for quantifying ocular dominance using the balancing technique.
AB  - INTRODUCTION AND PURPOSE: To develop a chart for the clinical setting that can
      quantify ocular dominance by using the modified balancing technique, a method
      based on binocular rivalry. METHODS: In 100 healthy young volunteers, rightward
      tilted and leftward-tilted square-wave gratings were presented to the right and
      left eye, respectively. A newly designed chart employing balancing techniques
      based on binocular rivalry was used in conjunction with a viewer. Target contrast
      in the nondominant eyes was fixed at 100%, while in the dominant eyes it was
      varied from 100% to 10% during ten steps that used a square-wave grating of 2
      cycles per degree and which were 4 degrees  in size. By varying the contrast of
      the dominant eye, a "reversal point," which is where the exclusive visibility
      time or the conscious perception frequency of the nondominant eye exceeds the
      dominant eye, is revealed. This can be used to assess the magnitude of the ocular
      dominance. RESULTS: Ocular dominance magnitude results indicated there was a good
      correlation between the modified and original balancing techniques. The modified
      balancing technique also showed high measurement repeatability. CONCLUSIONS: A
      chart that uses the modified balancing technique for ocular dominance
      examinations can be used as a simple test to quantify ocular dominance within
      clinical settings.

PMID- 22848116
TI  - Vision screening across the world.
AB  - INTRODUCTION: Pediatric vision screening is a global need. The International
      Orthoptic Association (IOA), comprised of fifteen full member countries and five
      associate member countries, is an excellent source of information to determine
      the current state of international vision screening efforts globally. METHODS: An
      e-mail survey was sent to representatives of member countries of the IOA.
      RESULTS: Of the eighteen surveys returned, 89% of countries have pediatric vision
      screening programs, 44% have a national program, 56% are government funded, and
      28% are obligatory. CONCLUSION: This survey sheds light on the state of
      international pediatric vision screening. Countries may use this information to
      help develop new methods and improve existing ones in order to enhance vision
      screening globally.

PMID- 22848117
TI  - Visual acuity assessment of children with special needs.
AB  - INTRODUCTION AND PURPOSE: A number of studies have evaluated visual acuity (VA)
      of special needs children, but no analyses of the parents' perception of VA
      testing or the utilization of VA test results by pediatric ophthalmologists have
      been reported. PATIENTS AND METHODS: Special needs children referred for an
      initial VA test (Teller Acuity Cards) during a 2-year period were enrolled (n =
      309). Within the overall cohort, twenty consecutive parents whose child attended
      during a 6-week period completed a Parent Questionnaire before and after VA
      testing. Also, 58 parents of infants with cortical visual impairment (CVI)
      completed the Parental Stress Index-Short Form (PSI-SF) before VA testing and 3
      months later. Referring pediatric ophthalmologists (n = 12) completed a Physician
      Questionnaire. RESULTS: VA testing was associated with parents reporting
      increased knowledge scores and decreased concerns about their children's vision
      on the Parent Questionnaire. VA testing was also associated with reduced Total
      and Parental Distress subscale scores on the PSI-SF by parents of infants with
      CVI. Ophthalmologists reported that VA results were useful in diagnosis and
      clinical management and provided new information to parents, Early Childhood
      Intervention programs, schools, and social agencies. CONCLUSION: VA testing is of
      benefit in children with special needs to both their parents and
      ophthalmologists, providing quantitative information about visual impairment and
      reducing stress experienced by parents.

PMID- 22848118
TI  - Franciscus Cornelis Donders (1818-1889): Dutch biologist, physiologist, and
      ophthalmologist.

PMID- 22848120
TI  - Increased consumption of healthcare services a certain future.

PMID- 22848121
TI  - The future of orthoptics.

PMID- 22848122
TI  - This year's issue.

PMID- 22848123
TI  - The absence of alternative oxidase AOX1A results in altered response of
      photosynthetic carbon assimilation to increasing CO(2) in Arabidopsis thaliana.
AB  - In higher plants, the mitochondrial electron transport chain has non
      phosphorylating alternative pathways that include the alternative terminal
      oxidase (AOX). This alternative pathway has been suggested to act as a sink for
      dissipating excess reducing power, minimizing oxidative stress and possibly
      optimizing photosynthesis in response to changing conditions. The expression
      patterns of the AOX genes have been well characterized under different growth
      conditions, particularly in response to light and temperature stress.
      Additionally, it has been suggested that mitochondrial electron transport is
      important for avoiding chloroplast over-reduction and balancing energy
      partitioning among photosynthesis, photorespiration and respiration. Nonetheless,
      the role AOX plays in optimizing photosynthetic carbon metabolism is unclear.
      Therefore, the response of photosynthesis to the disruption of AOX was
      investigated in the Arabidopsis thaliana T-DNA mutant aox1a (SALK_084897). Gas
      exchange analysis revealed a lower net CO(2) assimilation rate (A) at high CO(2)
      concentrations in the aox1a mutant compared to wild type. This decrease in A was
      accompanied by a lower maximum electron transport rate and quantum yield of PSII,
      and higher excitation pressure on PSII and non-photochemical quenching. The aox1a
      mutant also exhibited a lower estimated rate of ribulose 1,5-bisphosphate
      regeneration, and the ribulose 1,5-bisphosphate content was lower at high CO(2)
      concentrations, suggesting an ATP limitation of the Calvin-Benson cycle.
      Additionally, the activity of the malate-oxaloacetate shuttle was lower in the
      mutant compared to wild type. These results indicate that AOX is important for
      optimizing rates of photosynthetic CO(2) assimilation in response to rising CO(2)
      concentration by balancing the NAD(P)H/ATP ratio and rates of ribulose 1,5
      bisphosphate regeneration within the chloroplast.

PMID- 22848124
TI  - A PixD--PapB chimeric protein reveals the function of the BLUF domain C-terminal
      alpha-helices for light signal transduction.
AB  - Blue light-using flavin (BLUF) proteins form a subfamily of blue light
      photoreceptors, are found in many bacteria and algae, and are further classified
      according to their structures. For one type of BLUF-containing protein, e.g.
      PixD, the central axes of its two C-terminal alpha-helices are perpendicular to
      the beta-sheet of its N-terminal BLUF domain. For another type, e.g. PapB, the
      central axes of its two C-terminal alpha-helices are parallel to its BLUF domain
      beta-sheet. However, the functional significance of the different orientations
      with respect to phototransduction is not clear. For the study reported herein, we
      constructed a chimeric protein, Pix0522, containing the core of the PixD BLUF
      domain and the C-terminal region of PapB, including the two alpha-helices, and
      characterized its biochemical and spectroscopic properties. Fourier transform
      infrared spectroscopy detected similar light-induced conformational changes in
      the C-terminal alpha-helices of Pix0522 and PapB. Pix0522 interacts with and
      activates the PapB-interacting enzyme, PapA, demonstrating the functionality of
      Pix0522. These results provide direct evidence that the BLUF C-terminal alpha
      helices function as an intermediary that accepts the flavin-sensed blue light
      signal and transmits it downstream during phototransduction.

PMID- 22848127
TI  - Segmentation, Inference and Classification of Partially Overlapping
      Nanoparticles.
AB  - This paper presents a method that enables automated morphology analysis of
      partially overlapping nanoparticles in electron micrographs. In the undertaking
      of morphology analysis, three tasks appear necessary: separate individual
      particles from an agglomerate of overlapping nano-objects; infer the particle's
      missing contours; and ultimately, classify the particles by shape based on their
      complete contours. Our specific method adopts a two-stage approach: the first
      stage executes the task of particle separation, and the second stage conducts
      simultaneously the tasks of contour inference and shape classification. For the
      first stage, a modified ultimate erosion process is developed for decomposing a
      mixture of particles into markers, and then, an edge-to-marker association method
      is proposed to identify the set of evidences that eventually delineate individual
      objects. We also provided theoretical justification regarding the separation
      capability of the first stage. In the second stage, the set of evidences become
      inputs to a Gaussian mixture model on B-splines, the solution of which leads to
      the joint learning of the missing contour and the particle shape. Using twelve
      real electron micrographs of overlapping nanoparticles, we compare the proposed
      method with seven state-of-the-art methods. The results show the superiority of
      the proposed method in terms of particle recognition rate. 

PMID- 22848125
TI  - Psychological maltreatment.
AB  - Psychological or emotional maltreatment of children may be the most challenging
      and prevalent form of child abuse and neglect. Caregiver behaviors include acts
      of omission (ignoring need for social interactions) or commission (spurning,
      terrorizing); may be verbal or nonverbal, active or passive, and with or without
      intent to harm; and negatively affect the child's cognitive, social, emotional,
      and/or physical development. Psychological maltreatment has been linked with
      disorders of attachment, developmental and educational problems, socialization
      problems, disruptive behavior, and later psychopathology. Although no evidence
      based interventions that can prevent psychological maltreatment have been
      identified to date, it is possible that interventions shown to be effective in
      reducing overall types of child maltreatment, such as the Nurse Family
      Partnership, may have a role to play. Furthermore, prevention before occurrence
      will require both the use of universal interventions aimed at promoting the type
      of parenting that is now recognized to be necessary for optimal child
      development, alongside the use of targeted interventions directed at improving
      parental sensitivity to a child's cues during infancy and later parent-child
      interactions. Intervention should, first and foremost, focus on a thorough
      assessment and ensuring the child's safety. Potentially effective treatments
      include cognitive behavioral parenting programs and other psychotherapeutic
      interventions. The high prevalence of psychological abuse in advanced Western
      societies, along with the serious consequences, point to the importance of
      effective management. Pediatricians should be alert to the occurrence of
      psychological maltreatment and identify ways to support families who have risk
      indicators for, or evidence of, this problem.

PMID- 22848128
TI  - Babytalk: understanding and generating simple image descriptions.
AB  - We present a system to automatically generate natural language descriptions from
      images. This system consists of two parts. The first part, content planning,
      smooths the output of computer vision-based detection and recognition algorithms
      with statistics mined from large pools of visually descriptive text to determine
      the best content words to use to describe an image. The second step, surface
      realization, chooses words to construct natural language sentences based on the
      predicted content and general statistics from natural language. We present
      multiple approaches for the surface realization step and evaluate each using
      automatic measures of similarity to human generated reference descriptions. We
      also collect forced choice human evaluations between descriptions from the
      proposed generation system and descriptions from competing approaches. The
      proposed system is very effective at producing relevant sentences for images. It
      also generates descriptions that are notably more true to the specific image
      content than previous work.

PMID- 22848131
TI  - Incremental fusion of Structure-from-Motion and GPS using constrained bundle
      adjustments.
AB  - Two problems occur when bundle adjustment (BA) is applied on long image
      sequences: large calculation time and drift (or error accumulation). In recent
      work, the calculation time is reduced by local BAs applied in an incremental
      scheme. The drift may be reduced by fusion of GPS and Structure-from-Motion. An
      existing fusion method is BA minimizing a weighted sum of image and GPS errors.
      This paper introduces two constrained BAs for fusion which enforce an upper bound
      for the reprojection error. These BAs are alternatives to the existing fusion BA
      which does not guarantee a small reprojection error and requires a weight as
      input. Then, the three fusion BAs are integrated in an incremental Structure-from
      Motion method based on local BA. Last, we will compare the fusion results on long
      monocular image sequences and low cost GPS.

PMID- 22848130
TI  - Fast cost-volume filtering for visual correspondence and beyond.
AB  - Many computer vision tasks can be formulated as labeling problems. The desired
      solution is often a spatially smooth labeling where label transitions are aligned
      with color edges of the input image. We show that such solutions can be
      efficiently achieved by smoothing the label costs with a very fast edge
      preserving filter. In this paper, we propose a generic and simple framework
      comprising three steps: 1) constructing a cost volume, 2) fast cost volume
      filtering, and 3) Winner-Takes-All label selection. Our main contribution is to
      show that with such a simple framework state-of-the-art results can be achieved
      for several computer vision applications. In particular, we achieve 1) disparity
      maps in real time whose quality exceeds those of all other fast (local)
      approaches on the Middlebury stereo benchmark, and 2) optical flow fields which
      contain very fine structures as well as large displacements. To demonstrate
      robustness, the few parameters of our framework are set to nearly identical
      values for both applications. Also, competitive results for interactive image
      segmentation are presented. With this work, we hope to inspire other researchers
      to leverage this framework to other application areas.

PMID- 22848132
TI  - Wang-Landau Monte Carlo-based tracking methods for abrupt motions.
AB  - We propose a novel tracking algorithm based on the Wang-Landau Monte Carlo (WLMC)
      sampling method for dealing with abrupt motions efficiently. Abrupt motions cause
      conventional tracking methods to fail because they violate the motion smoothness
      constraint. To address this problem, we introduce the Wang-Landau sampling method
      and integrate it into a Markov Chain Monte Carlo (MCMC)-based tracking framework.
      By employing the novel density-of-states term estimated by the Wang-Landau
      sampling method into the acceptance ratio of MCMC, our WLMC-based tracking method
      alleviates the motion smoothness constraint and robustly tracks the abrupt
      motions. Meanwhile, the marginal likelihood term of the acceptance ratio
      preserves the accuracy in tracking smooth motions. The method is then extended to
      obtain good performance in terms of scalability, even on a high-dimensional state
      space. Hence, it covers drastic changes in not only position but also scale of a
      target. To achieve this, we modify our method by combining it with the N-fold way
      algorithm and present the N-Fold Wang-Landau (NFWL)-based tracking method. The N
      fold way algorithm helps estimate the density-of-states with a smaller number of
      samples. Experimental results demonstrate that our approach efficiently samples
      the states of the target, even in a whole state space, without loss of time, and
      tracks the target accurately and robustly when position and scale are changing
      severely.

PMID- 22848133
TI  - Spring level sets: a deformable model representation to provide interoperability
      between meshes and level sets.
AB  - A new type of deformable model is presented that merges meshes and level sets
      into one representation to provide interoperability between methods designed for
      either. This includes the ability to circumvent the CFL time step restriction for
      methods that require large step sizes. The key idea is to couple a constellation
      of disconnected triangular surface elements (springls) with a level set that
      tracks the moving constellation. The target application for Spring Level Sets
      (SpringLS) is to implement comprehensive imaging pipelines that require a mixture
      of deformable model representations to achieve the best performance. We
      demonstrate how to implement key components of a comprehensive imaging pipeline
      with SpringLS, including image segmentation, registration, tracking, and
      atlasing.

PMID- 22848134
TI  - An efficient alignment algorithm for searching simple pseudoknots over long
      genomic sequence.
AB  - Structural alignment has been shown to be an effective computational method to
      identify structural noncoding RNA(ncRNA) candidates as ncRNAs are known to be
      conserved in secondary structures. However, the complexity of the structural
      alignment algorithms becomes higher when the structure has pseudoknots. Even for
      the simplest type of pseudoknots (simple pseudoknots), the fastest algorithm runs
      in O(mn3) time, where m, n are the length of the query ncRNA (with known
      structure) and the length of the target sequence (with unknown structure),
      respectively. In practice, we are usually given a long DNA sequence and we try to
      locate regions in the sequence for possible candidates of a particular ncRNA.
      Thus, we need to run the structural alignment algorithm on every possible region
      in the long sequence. For example, finding candidates for a known ncRNA of length
      100 on a sequence of length 50,000, it takes more than one day. In this paper, we
      provide an efficient algorithm to solve the problem for simple pseudoknots and it
      is shown to be 10 times faster. The speedup stems from an effective pruning
      strategy consisting of the computation of a lower bound score for the optimal
      alignment and an estimation of the maximum score that a candidate can achieve to
      decide whether to prune the current candidate or not.

PMID- 22848135
TI  - Improving protein-protein interaction pair ranking with an integrated global
      association score.
AB  - Protein-protein interaction (PPI) database curation requires text-mining systems
      that can recognize and normalize interactor genes and return a ranked list of PPI
      pairs for each article. The order of PPI pairs in this list is essential for ease
      of curation. Most of the current PPI pair ranking approaches rely on association
      analysis between the two genes in the pair. However, we propose that ranking an
      extracted PPI pair by considering both the association between the paired genes
      and each of those genes' global associations with all other genes mentioned in
      the paper can provide a more reliable ranked list. In this work, we present a
      composite interaction score that considers not only the association score between
      two interactors (pair association score) but also their global association
      scores. We test three representative data fusion algorithms to estimate this
      global association score-two Borda-Fuse models and one linear combination model
      (LCM). The three estimation methods are evaluated using the data set of the
      BioCreative II.5 Interaction Pair Task (IPT) in terms of area under the
      interpolated precision/recall curve (AUC iP/R). Our experimental results indicate
      that using LCM to estimate the global association score can boost the AUC iP/R
      score from 0.0175 to 0.2396, outperforming the best BioCreative II.5 IPT system.

PMID- 22848136
TI  - Multiscale modeling and analysis of planar cell polarity in the Drosophila wing.
AB  - Modeling across multiple scales is a current challenge in Systems Biology,
      especially when applied to multicellular organisms. In this paper, we present an
      approach to model at different spatial scales, using the new concept of
      Hierarchically Colored Petri Nets (HCPN). We apply HCPN to model a tissue
      comprising multiple cells hexagonally packed in a honeycomb formation in order to
      describe the phenomenon of Planar Cell Polarity (PCP) signaling in Drosophila
      wing. We have constructed a family of related models, permitting different
      hypotheses to be explored regarding the mechanisms underlying PCP. In addition
      our models include the effect of well-studied genetic mutations. We have applied
      a set of analytical techniques including clustering and model checking over time
      series of primary and secondary data. Our models support the interpretation of
      biological observations reported in the literature.

PMID- 22848137
TI  - A fast and practical approach to genotype phasing and imputation on a pedigree
      with erroneous and incomplete information.
AB  - The MINIMUM-RECOMBINANT HAPLOTYPE CONFIGURATION problem (MRHC) has been highly
      successful in providing a sound combinatorial formulation for the important
      problem of genotype phasing on pedigrees. Despite several algorithmic advances
      that have improved the efficiency, its applicability to real data sets has been
      limited since it does not take into account some important phenomena such as
      mutations, genotyping errors, and missing data. In this work, we propose the
      MINIMUM-RECOMBINANT HAPLOTYPE CONFIGURATION WITH BOUNDED ERRORS problem (MRHCE),
      which extends the original MRHC formulation by incorporating the two most common
      characteristics of real data: errors and missing genotypes (including untyped
      individuals). We describe a practical algorithm for MRHCE that is based on a
      reduction to the well-known Satisfiability problem (SAT) and exploits recent
      advances in the constraint programming literature. An experimental analysis
      demonstrates the biological soundness of the phasing model and the effectiveness
      (on both accuracy and performance) of the algorithm under several scenarios. The
      analysis on real data and the comparison with state-of-the-art programs reveals
      that our approach couples better scalability to large and complex pedigrees with
      the explicit inclusion of genotyping errors into the model.

PMID- 22848138
TI  - Rough-fuzzy clustering for grouping functionally similar genes from microarray
      data.
AB  - Gene expression data clustering is one of the important tasks of functional
      genomics as it provides a powerful tool for studying functional relationships of
      genes in a biological process. Identifying coexpressed groups of genes represents
      the basic challenge in gene clustering problem. In this regard, a gene clustering
      algorithm, termed as robust rough-fuzzy c-means, is proposed judiciously
      integrating the merits of rough sets and fuzzy sets. While the concept of lower
      and upper approximations of rough sets deals with uncertainty, vagueness, and
      incompleteness in cluster definition, the integration of probabilistic and
      possibilistic memberships of fuzzy sets enables efficient handling of overlapping
      partitions in noisy environment. The concept of possibilistic lower bound and
      probabilistic boundary of a cluster, introduced in robust rough-fuzzy c-means,
      enables efficient selection of gene clusters. An efficient method is proposed to
      select initial prototypes of different gene clusters, which enables the proposed
      c-means algorithm to converge to an optimum or near optimum solutions and helps
      to discover coexpressed gene clusters. The effectiveness of the algorithm, along
      with a comparison with other algorithms, is demonstrated both qualitatively and
      quantitatively on 14 yeast microarray data sets.

PMID- 22848139
TI  - Computational reconstruction of transcriptional relationships from ChIP-chip
      data.
AB  - Eukaryotic gene transcription is a complex process, which requires the
      orchestrated recruitment of a large number of proteins, such as sequence-specific
      DNA binding factors, chromatin remodelers and modifiers, and general
      transcription machinery, to regulatory regions. Previous works have shown that
      these regulatory proteins favor specific organizational theme along promoters.
      Details about how they cooperatively regulate transcriptional process, however,
      remain unclear. We developed a method to reconstruct a Bayesian network (BN)
      model representing functional relationships among various transcriptional
      components. The positive/negative influence between these components was measured
      from protein binding and nucleosome occupancy data and embedded into the model.
      Application on S.cerevisiae ChIP-Chip data showed that the proposed method can
      recover confirmed relationships, such as Isw1-Pol II, TFIIH-Pol II, TFIIB-TBP,
      Pol II-H3K36Me3, H3K4Me3-H3K14Ac, etc. Moreover, it can distinguish colocating
      components from functionally related ones. Novel relationships, e.g., ones
      between Mediator and chromatin remodeling complexes (CRCs), and the combinatorial
      regulation of Pol II recruitment and activity by CRCs and general transcription
      factors (GTFs), were also suggested. CONCLUSION: protein binding events during
      transcription positively influence each other. Among contributing components,
      GTFs and CRCs play pivotal roles in transcriptional regulation. These findings
      provide insights into the regulatory mechanism.

PMID- 22848141
TI  - Punctal stenosis: definition, diagnosis, and treatment.
AB  - Acquired punctal stenosis is a condition in which the external opening of the
      lacrimal canaliculus is narrowed or occluded. This condition is a rare cause of
      symptomatic epiphora, but its incidence may be higher in patients with chronic
      blepharitis, in those treated with various topical medications, including
      antihypertensive agents, and especially in patients treated with taxanes for
      cancer. The purpose of this review is to cover the medical literature, focusing
      in particular on definition, incidence, risk factors, etiology and treatment
      options.

PMID- 22848140
TI  - Transconjunctival 25-gauge pars plana vitrectomy and internal limiting membrane
      peeling for chronic macular edema.
AB  - BACKGROUND: The purpose of this study was to investigate the visual and anatomic
      outcomes in patients with chronic macular edema who underwent 25-gauge pars plana
      vitrectomy with internal limiting membrane peeling. METHODS: This study was a
      retrospective chart review of 24 eyes from 21 patients who underwent 25-gauge
      pars plana vitrectomy and indocyanine green-assisted internal limiting membrane
      peeling for chronic macular edema. Preoperative and postoperative spectral-domain
      optical coherence tomography (OCT) was examined for macular thickness and macular
      volume. Outcomes and variables were analyzed using the two-tailed t-test and
      Spearman's rank correlation coefficient. RESULTS: Twenty-four eyes from 11 men
      and 10 women of mean age 69 (range 55-84) years were included. Four patients
      (17%) had chronic macular edema from uveitis, four (17%) from retinal vein
      occlusion, and 16 (67%) from diabetes. Mean visual acuity was 20/103
      preoperatively and 20/87 postoperatively (P = 0.55). Sixty-three percent of the
      eyes had improved vision (47% better than 20/40), 21% maintained the same vision,
      and 17% had worse vision. Forty-seven percent of improved eyes and 30% of total
      eyes gained more than two lines of visual acuity (range -9 to +7 lines). Mean
      macular thickness was 455 MUm preoperatively and 396 MUm postoperatively (P =
      0.29). Mean macular volume was 7.9 mm(3) preoperatively and 7.5 mm(3)
      postoperatively (P = 0.51). The strongest predictor of postoperative visual
      acuity was initial visual acuity (r = 0.673, P = 0.0003). CONCLUSION: Even though
      a majority of patients had improved vision and decreased macular thickening after
      25-gauge pars plana vitrectomy with internal limiting membrane peeling for
      chronic macular edema of various etiologies, the difference in visual acuity or
      macular thickening did not reach statistical significance.

PMID- 22848142
TI  - Comparative study of trabeculectomy using single sutures versus releasable
      sutures.
AB  - BACKGROUND: The purpose of this study was to compare the outcomes of
      trabeculectomy using single sutures or releasable sutures. METHODS: This
      retrospective study analyzed the medical records of 61 patients who had undergone
      trabeculectomy using single sutures (n = 33, 54.1%) or releasable sutures (n =
      28, 45.9%). The scleral flap was secured with a mean 3.9 (range 3-5) single
      sutures in 33 patients and with three releasable sutures in 28 patients. Primary
      outcomes were the success rate, based on intraocular pressure and medication
      usage, and the frequency of complications and post-surgical interventions. The
      criteria used to determine complete success were, first, intraocular pressure <
      18 mmHg and, second, <=21 mmHg and >=20% intraocular pressure reduction without
      glaucoma medication. RESULTS: All patients had an intraocular pressure <= 21
      mmHg; 87.5% in the single suture group and 92.6% in the releasable suture group
      had an intraocular pressure < 18 mmHg at 24 months. There was a highly
      significant reduction in intraocular pressure to baseline values in both groups
      at the last visit. Applying the first criterion, complete success was achieved in
      57.6% of patients with single sutures and 71.4% with releasable sutures, and
      based on the second criterion, 66.7% and 71.4%, respectively. No significant
      difference was found between the groups with regard to intraocular pressure, or
      success or complication rates. CONCLUSION: The results of trabeculectomy using
      single sutures or releasable sutures are equivalent. Therefore, the choice of
      suture technique should be based on individual patient requirements and surgeon
      experience.

PMID- 22848143
TI  - Long-term follow-up of choroidal neovascularization secondary to angioid streaks:
      case series and literature review.
AB  - BACKGROUND: The purpose of this paper is to report the clinical course of
      choroidal neovascularization (CNV) secondary to angioid streaks and the outcomes
      in response to different treatment modalities. METHODS: This was a case series of
      two consecutive patients (four eyes) with CNV secondary to angioid streaks.
      Visual acuity, ophthalmological examination, color photographs, fluorescein
      angiography, and optical coherence tomography were used to assess the outcomes of
      treatment. RESULTS: Two eyes were treated with photodynamic therapy for subfoveal
      choroidal neovascular membrane, one eye underwent thermal laser photocoagulation
      for extrafoveal CNV followed by intravitreal bevacizumab for subfoveal CNV, and
      one eye underwent intravitreal bevacizumab for subfoveal CNV. The follow-up
      period was 4-6 years. The final visual acuities of all eyes were 20/300 or worse
      with large submacular fibrosis. CONCLUSION: CNV secondary to angioid streaks in
      these two patients had a poor prognosis despite undergoing different types of
      treatment. Poor outcome was likely related to frequent recurrence and newly
      developed CNV, which remained a clinical concern in these cases.

PMID- 22848145
TI  - Comparison of central corneal thickness measurements using ultrasound pachymetry,
      ultrasound biomicroscopy, and the Artemis-2 VHF scanner in normal eyes.
AB  - PURPOSE: To compare the precision of central corneal thickness (CCT) measurements
      taken with the handheld ultrasound pachymeter (USP), ultrasound biomicroscopy
      (UBM), and the Artemis-2 very high frequency ultrasound scanner (VHFUS) on normal
      subjects. DESIGN: Prospective study. METHODS: One eye from each of 61 normal
      subjects was randomly selected for this study. The measurements of the CCT were
      taken with the USP, VHFUS, and UBM. Results were compared statistically using
      repeated-measures analysis of variance (ANOVA), Pearson's correlation
      coefficient, and limits of agreement. RESULTS: The average CCT (+/- standard
      deviation) was 530.1 +/- 30.5 MUm, 554.9 +/- 31.7 MUm, and 559.5 +/- 30.7 MUm for
      UBM, VHFUS, and USP respectively. The intraobserver repeatability analyses of
      variance are not significant for USP, UBM, and VHFUS. P-values were 0.17, 0.19,
      and 0.37 respectively. Repeated-measures ANOVA showed a significant difference
      between the three different methods of measuring CCT (P = 0.0001). The ANOVA test
      revealed no statistically significant difference between USP and VHFUS (P >
      0.05), yet statistical significant differences with UBM versus USP and UBM versus
      VHFUS (P < 0.001). There were high correlations between the three instruments (P
      < 0.0001). The mean differences (and upper/lower limits of agreement) for CCT
      measurements were 29.4 +/- 14.3 (2.7/56), 4.6 +/- 8.6 (-14.7/23.8), and -24.8 +/-
      13.1 (-50.4/0.8) for USP versus UBM, USP versus VHFUS, and UBM versus VHFUS,
      respectively. CONCLUSION: The UBM produces CCT measurements that vary
      significantly from those returned by the USP and the VHFUS, suggesting that the
      UBM may not be used interchangeably with either equipment for monitoring the CCT
      in the clinical setting.

PMID- 22848146
TI  - The effect of phacoemulsification on late bleb failure or intraocular pressure in
      patients with glaucoma: a systematic review.
AB  - The purpose of our systematic review is to document the adverse events that
      follow phacoemulsification in eyes with trabeculectomy due to glaucoma and to
      determine whether phacoemulsification jeopardizes the survival of the
      trabeculectomy. Our research was based on English- and non-English-language
      articles obtained using the Medline, Embase, Web of Science and Scopus databases.
      Additional studies were identified by searching bibliographies in the British
      Library and abstracts presented at the Association for Research in Vision and
      Ophthalmology annual meetings. Search terms included randomized controlled trial,
      controlled clinical trial, random allocation, double-blind method, matched
      studies and trabeculectomy failure, glaucoma-filtering operation failure, bleb
      failure and cataract surgery or phacoemulsification. Only prospective or
      retrospective matched studies testing the survival of a trabeculectomy alone
      versus clear corneal phacoemulsification after a trabeculectomy in patients with
      glaucoma were included. Data were independently extracted by two authors using
      predefined data fields. PubMed yielded 152 results, Scopus 235, Embase 222, and
      Web of Science (science citation index) 216. We read the abstracts of all the
      trials, and after reading the full text of 31 studies, we decided that 13 studies
      should be comprehensively evaluated. Current evidence does not allow us to draw
      safe conclusions on the scientific question so far.

PMID- 22848147
TI  - Comparison of timolol 0.5% + brimonidine 0.2% + dorzolamide 2% versus timolol
      0.5% + brimonidine 0.2% in a Mexican population with primary open-angle glaucoma
      or ocular hypertension.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of
      two fixed combinations, ie, timolol 0.5% + brimonidine 0.2% + dorzolamide 2%
      (TBD) versus timolol 0.5% + brimonidine 0.2% (TB) in patients with primary open
      angle glaucoma or ocular hypertension. METHODS: We performed a 3-month,
      randomized, double-blind study in patients with primary open-angle glaucoma or
      ocular hypertension and an intraocular pressure of 21-30 mmHg. Patients were
      randomly assigned to receive one drop of TBD or TB twice a day. The primary
      efficacy endpoint was change in intraocular pressure after 3 months of treatment.
      Safety measures were assessed by the presence of adverse events. RESULTS: Mean
      baseline intraocular pressure was similar at 8 am and 4 pm in the treatment
      groups (TBD 22.3 +/- 0.9 mmHg, TB 22.4 +/- 1.8 mmHg, P = 0.558; TBD 19.02 +/-
      1.3, TB 19.08 +/- 1.2, P = 0.536, respectively). At the end of the study, the
      mean intraocular pressure was significantly lower in the TBD group at both 8 am
      (16.19 +/- 2.0 mmHg versus 18.35 +/- 1.4 mmHg, P = 0.000) and 4 pm (14.74 +/- 2.4
      mmHg versus 16.77 +/- 1.4 mmHg, P = 0.000). CONCLUSION: Fixed-combination TBD was
      more effective than fixed-combination TB for reducing IOP in patients with
      primary open-angle glaucoma.

PMID- 22848148
TI  - Effect of biologic therapy on radiological progression in rheumatoid arthritis:
      what does it add to methotrexate?
AB  - There have been substantial advances in the treatment of rheumatoid arthritis in
      recent years. Traditional disease-modifying antirheumatic drugs (DMARDs) have
      been shown to have small effects on the progression of radiographic damage. This
      quantitative overview summarizes the evidence for biologic DMARDs and
      radiographic damage either alone or in combination with methotrexate. Two
      outcomes were used (standardized mean difference and odds of progression). A
      total of 21 trials were identified of which 18 had useable data. For biologic
      monotherapy, tocilizumab, adalimumab, and etanercept were significantly better
      than methotrexate, with tocilizumab ranking first in both outcomes while
      golimumab was ineffective in both outcomes. For a biologic in combination with
      methotrexate compared with methotrexate alone, most therapies studied
      (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab)
      were effective at slowing X-ray progression using either outcome, with infliximab
      ranking first in both outcomes. The exceptions to this were golimumab (no effect
      on standardized mean difference) and abatacept (no effect on odds of
      progression). This effect was additional to methotrexate; thus, the overall
      benefit is moderate to large in magnitude, which is clearly of major clinical
      significance for sufferers of rheumatoid arthritis and supports the use of
      biologic DMARDs in those with a poor disease prognosis.

PMID- 22848150
TI  - Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis
      patients and previous TNFalpha blocker failure.
AB  - PURPOSE: To assess the efficacy of one course of rituximab (two 1-g doses)
      compared to an alternative tumor necrosis factor-alpha (TNFalpha) blocker in
      rheumatoid arthritis patients who had experienced one previous TNFalpha blocker
      failure (eg, etanercept, adalimumab, or infliximab). PATIENTS AND METHODS: The
      efficacy of both treatments was studied in this retrospective, multicenter,
      noninterventional cohort study with 196 patients. All patients had active
      rheumatoid arthritis defined by a Disease Activity Score-28 of >=3.2 despite
      having TNFalpha blocker therapy, and were followed over 6.6 months on average
      after switching to rituximab versus a second TNFalpha blocker (ie, switching to
      etanercept, adalimumab, or infliximab) at baseline. RESULTS: At baseline, both
      cohorts showed similar demographic and disease-related characteristics (including
      Disease Activity Score-28). At the end of observation, mean Disease Activity
      Score-28 was significantly lower after treatment with rituximab than with a
      second TNFalpha blocker (-1.64 [95% confidence interval: -1.92; -1.36] versus 
      1.19 [95% confidence interval: -1.42; -0.96], P = 0.013). This difference between
      the two groups was even more pronounced when patients were seropositive for
      rheumatoid factor (-1.66 versus -1.17, P = 0.018) and anti-cyclic citrullinated
      peptide antibodies (-1.75 versus -1.06, P = 0.002). More rituximab-treated
      patients achieved good European League Against Rheumatism response than TNFalpha
      blocker-treated patients (30% versus 15%), and less patients were nonresponders
      (22% versus 35%) according to European League Against Rheumatism criteria (P =
      0.022, chi-squared test). CONCLUSION: Treatment with rituximab was more effective
      than a second TNFalpha blocker therapy in rheumatoid arthritis patients after
      failure of the first TNFalpha blocker. It was found that anti-cyclic
      citrullinated peptide antibodies may be a useful predictive biomarker for
      response to rituximab in patients with TNFalpha blocker treatment failure.

PMID- 22848151
TI  - Psychometric properties of the Specific Thalassemia Quality of Life Instrument
      for adults.
AB  - BACKGROUND: No specific questionnaire has been developed to assess the health
      related quality of life of thalassemia patients. Thus, the main objective of this
      study was to develop, according to psychometric standards, a self-administered
      Specific Thalassemia Quality of Life Instrument (STQOLI) for adult patients.
      METHODS: First, a qualitative phase was conducted to generate items and identify
      domains using the critical analysis incident technique and a literature review. A
      list of easily comprehensible, non-redundant items was defined using the Delphi
      technique and a pilot study on ten thalassemia patients. This phase involved both
      patients and experts. The second step was a quantitative validation phase
      comprising a study of 128 thalassemia patients in a single hospital. It was
      designed to select items, identify dimensions, and measure reliability and
      internal and concurrent validity. The psychometric and scaling properties of the
      proposed 41-item Specific Thalassemia Quality of Life Instrument were then
      assessed among patients recruited from the Thalassemia Unit at the General
      Hospital of Nikaia, Greece. RESULTS: The final questionnaire had 41 items
      comprising four main domains and one global item about general health. The
      factorial structure was satisfactory (loading > 0.40 on each factor of the four
      domains for all items). Interscale correlations ranged from 0.06 to 0.78,
      Cronbach's alpha-coefficients were 0.78 for the psychosocial domain, 0.77 for the
      chelation domain, 0.72 for the transfusion domain, 0.81 for the disease and
      symptoms domain, and 0.840 for the total score of the questionnaire. CONCLUSION:
      The 41-item Specific Thalassemia Quality of Life Instrument seems to be a valid
      tool for assessing health-related quality of life for patients with thalassemia.
      More research is needed to explore the universal properties of the questionnaire.

PMID- 22848152
TI  - Diagnosis of airway obstruction in the elderly: contribution of the SARA study.
AB  - BACKGROUND: The choice between lower limit of normal or fixed value of forced
      expiratory volume in one second/forced vital capacity ratio (FEV(1)/FVC) < 0.70
      as the criterion for confirming airway obstruction is an open issue. In this
      study, we compared the criteria of lower limit of normal and fixed FEV(1)/FVC for
      diagnosis of airway obstruction, with a focus on healthy elderly people. METHODS:
      We selected 367 healthy nonsmoking subjects aged 65-93 years from 1971
      participants in the population-based SARA (Salute Respiratoria nell'Anziano,
      Italian for "Respiratory Health in the Elderly") study, analyzed their
      spirometric data, and tested the relationship between spirometric indices and
      anthropometric variables. The lower limit of normal for FEV(1)/FVC was calculated
      as the fifth percentile of the normal distribution for selected subjects.
      RESULTS: While FEV(1) and FVC decreased significantly with aging, the
      relationship between FEV(1)/FVC and age was not statistically significant in men
      or women. The lower limit of normal for FEV(1)/FVC was 0.65 in men and 0.67 in
      women. Fifty-five participants (15%) had FEV(1)/FVC < 0.70 and would have been
      inappropriately classified as obstructed according to the Global Initiative for
      Obstructive Lung Disease, American Thoracic Society/European Respiratory Society,
      and Canadian guidelines on chronic obstructive pulmonary disease. By applying
      different FEV(1)/FVC thresholds for the different age groups, as previously
      proposed in the literature, (0.70 for <70 years, 0.65 for 70-80 years, and 0.60
      for >80 years) the percentage of patients classified as obstructed decreased to
      6%. No subjects older than 80 years had an FEV(1)/FVC < 0.60. CONCLUSION: The
      present results confirm the inadequacy of FEV(1)/FVC < 0.70 as a diagnostic
      criterion for airway obstruction after the age of 65 years. FEV(1)/FVC < 0.65 and
      <0.67 (for men and women, respectively) could identify subjects with airway
      obstruction in such a population. Further reduction of the threshold after 80
      years is not justified.

PMID- 22848153
TI  - Clinical trial of community nurse mentoring to improve self-management in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) impacts on quality of
      life and is characterized by exacerbations, which increase health care
      utilization. Developing self-management behaviors of people with COPD is an
      attractive strategy to reduce exacerbations. METHODS: We investigated the effect
      of a program to increase self-management behaviors delivered by community health
      nurses, compared with usual care, on health-related quality of life and health
      care utilization in people with COPD following hospitalization. Participants were
      recruited during an admission to hospital and allocated according to domicile.
      The mentor role was to develop self-management strategies collaboratively over
      the 12-month study duration. Outcomes included quality of life and health care
      utilization. RESULTS: Linear mixed models analyses found a significant benefit in
      the physical functioning and general health components of the short-form SF-36
      questionnaire for the mentored arm, with the average difference between
      interventions being 5.60 and 4.14, respectively, over 12 months. Survival
      analysis using a combined endpoint of time to next acute exacerbation requiring
      rehospitalization or death found a significant benefit favoring the mentored
      group (P = 0.037). CONCLUSION: A mentoring program designed to improve self
      management behaviors in people with COPD following hospitalization increased some
      quality of life domains and improved important clinical outcomes.

PMID- 22848154
TI  - Efficacy of indacaterol 75 MUg versus fixed-dose combinations of formoterol
      budesonide or salmeterol-fluticasone for COPD: a network meta-analysis.
AB  - BACKGROUND: The purpose of this study was to update our network meta-analysis in
      order to compare the efficacy of indacaterol 75 MUg with that of a fixed-dose
      combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination
      salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive
      pulmonary disease (COPD) based on evidence identified previously in addition to
      two new randomized clinical trials. METHODS: Fifteen randomized, placebo
      controlled clinical trials including COPD patients were evaluated: indacaterol 75
      MUg once daily (n = 2 studies), indacaterol 150 MUg once daily (n = 5),
      indacaterol 300 MUg once daily (n = 4), FOR/BUD 9/160 MUg twice daily (n = 2),
      FOR/BUD 9/320 MUg twice daily (n = 2), SAL/FP 50/500 MUg twice daily (n = 4), and
      SAL/FP 50/250 MUg twice daily (n = 1). All trials were analyzed simultaneously
      using a Bayesian network meta-analysis and relative treatment effects between all
      regimens were obtained. Treatment-by-covariate interactions were included where
      possible to improve the similarity of the trials. Outcomes of interest were
      trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea
      index at 12 weeks. RESULTS: Based on the results without adjustment for
      covariates, indacaterol 75 MUg resulted in a greater improvement in FEV(1) at 12
      weeks compared with FOR/BUD 9/160 MUg (difference in change from baseline 0.09 L
      [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 MUg (0.07 L [0.03-0.11]) and
      was comparable with SAL/FP 50/250 MUg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 MUg
      (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only
      for indacaterol 75 MUg versus SAL/FP 50/500 MUg (-0.49 points [-1.87-0.89]).
      CONCLUSION: Based on results of a network meta-analysis with and without
      covariates, indacaterol 75 MUg is expected to be at least as efficacious as
      FOR/BUD (9/320 MUg and 9/160 MUg) and comparable with SAL/FP (50/250 MUg and
      50/500 MUg) in terms of lung function. In terms of breathlessness (transitional
      dyspnea index) at 12 weeks, the results are inconclusive given the limited data.

PMID- 22848155
TI  - The importance of knowing the home conditions of patients receiving long-term
      oxygen therapy.
AB  - PURPOSE: Long-term oxygen therapy (LTOT) is one of the main treatments for
      patients with chronic obstructive pulmonary disease. Patients receiving LTOT may
      have less than optimal home conditions and this may interfere with treatment. The
      objective of this study was, through home visits, to identify the characteristics
      of patients receiving LTOT and to develop knowledge regarding the home
      environments of these patients. METHODS: Ninety-seven patients with a mean age of
      69 plus or minus 10.5 years were evaluated. This study was a cross-sectional
      descriptive analysis. Data were collected during an initial home visit, using a
      questionnaire standardized for the study. The results were analyzed
      retrospectively. RESULTS: Seventy-five percent of the patients had chronic
      obstructive pulmonary disease, and 11% were active smokers. The patients' mean
      pulse oximetry values were 85.9% plus or minus 4.7% on room air and 92% plus or
      minus 3.9% on the prescribed flow of oxygen. Most of the patients did not use the
      treatment as prescribed and most used a humidifier. The extension hose had a mean
      length of 5 plus or minus 3.9 m (range, 1.5-16 m). In the year prior to the
      visit, 26% of the patients received emergency medical care because of respiratory
      problems. Few patients reported engaging in leisure activities. CONCLUSION: The
      home visit allowed us to identify problems and interventions that could improve
      the way LTOT is used. The most common interventions related to smoking cessation,
      concentrator maintenance and cleaning, use of a humidifier, and adjustments of
      the length of the connector hose. Therefore, the home visit is a very important
      tool in providing comprehensive care to patients receiving LTOT, especially those
      who show lack of adequate progress and those who show uncertainty about the
      treatment method.

PMID- 22848149
TI  - The effect of erythropoietin on normal and neoplastic cells.
AB  - Erythropoietin (Epo) is an essential hormone that binds and activates the Epo
      receptor (EpoR) resident on the surface of erythroid progenitor cells, thereby
      promoting erythropoiesis. Recombinant human erythropoietin has been used
      successfully for over 20 years to treat anemia in millions of patients. In
      addition to erythropoiesis, Epo has also been reported to have other effects,
      such as tissue protection and promotion of tumor cell growth or survival. This
      became of significant concern in 2003, when some clinical trials in cancer
      patients reported increased tumor progression and worse survival outcomes in
      patients treated with erythropoiesis-stimulating agents (ESAs). One of the
      potential mechanisms proffered to explain the observed safety issues was that
      functional EpoR was expressed in tumors and/or endothelial cells, and that ESAs
      directly stimulated tumor growth and/or antagonized tumor ablative therapies.
      Since then, numerous groups have performed further research evaluating this
      potential mechanism with conflicting data and conclusions. Here, we review the
      biology of endogenous Epo and EpoR expression and function in erythropoiesis, and
      evaluate the evidence pertaining to the expression of EpoR on normal
      nonhematopoietic and tumor cells.

PMID- 22848156
TI  - Clinical diaries in COPD: compliance and utility in predicting acute
      exacerbations.
AB  - BACKGROUND: Daily diaries are often used to collect data on disease activity, but
      are burdensome and compliance may be poor. Their use in chronic obstructive
      pulmonary disease (COPD) and impact on the prevention and treatment of
      exacerbations is poorly researched. METHODS: We investigated diary-keeping in
      COPD and ascertained items that best predicted emergency attendances for
      exacerbations. Participants in the active limb of a clinical trial in COPD kept
      daily diaries rating breathlessness, cough, sputum, physical activity, and use of
      reliever medication. RESULTS: Data on 55 participants, 67% of whom were female,
      showed that overall compliance with diary-keeping was 62%. Participants educated
      to primary school level only had lower compliance (P = 0.05). Twenty patients had
      at least one emergency attendance, in whom the relative risk of an acute
      exacerbation for an increase in item score rose from six days prior to
      hospitalization, most sharply in the last two days. Even for optimal combinations
      of items, the positive predictive value was poor, the best combination being
      cough, activity level, and inhaler use. CONCLUSION: Good compliance can be
      achieved using daily diaries in COPD, although this is worse in those with a poor
      educational level. Diary-keeping is not accurate in predicting acute
      exacerbations, but could be substantially simplified without loss of efficiency.

PMID- 22848157
TI  - Design, rationale, and baseline demographics of SEARCH I: a prospective cluster
      randomized study.
AB  - Questionnaires are available to identify patients at risk for several chronic
      diseases, including COPD, but are infrequently utilized in primary care. COPD is
      often underdiagnosed, while at the same time the US Preventive Services Task
      Force recommends against spirometric screening for COPD in asymptomatic adults.
      Use of a symptom-based questionnaire and subsequent handheld spirometric device
      depending on the answers to the questionnaire is a promising approach to identify
      patients at risk for COPD. Screening, Evaluating and Assessing Rate CHanges of
      diagnosing respiratory conditions in primary care 1 (SEARCH I) was a prospective
      cluster-randomized study in 168 US primary care practices evaluating the effect
      of the COPD-Population Screener (COPD-PSTM) questionnaire. The effect of this
      questionnaire alone or sequentially with the handheld copd-6(TM) device was
      evaluated on new diagnoses of COPD and on respiratory diagnostic practice
      patterns (including referrals for pulmonary function testing, referrals to
      pulmonologists, new diagnoses of COPD, and new respiratory medication
      prescriptions). Participating practices entered a total of 9704 consecutive
      consenting subjects aged >= 40 years attending primary care clinics. Study arm
      results were compared for new COPD diagnosis rates between usual care and (1)
      COPD-PS plus copd-6 and (2) COPD-PS alone. A cluster-randomization design allowed
      comparison of the intervention effects at the practice level instead of
      individuals being the subjects of the intervention. Regional principal
      investigators controlled the flow of study information to sub-investigators at
      participating practices to reduce observation bias (Hawthorne effect). The
      results of SEARCH I, to be published subsequently, will provide insight into the
      real world utility of the COPD-PS as well as two-stage COPD case finding with
      COPD-PS and copd-6.

PMID- 22848158
TI  - Development of an MRI-visible nonviral vector for siRNA delivery targeting
      gastric cancer.
AB  - An antibody-directed nonviral vector, polyethylene glycol-grafted
      polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles
      and a gastric cancer-associated CD44v6 single-chain variable fragment
      (scFv(CD44v6),-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting
      and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering
      RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and
      scFv(CD44v6)-PEG-g-PEI-SPION was carried out, including siRNA condensation
      capacity, cell viability, and transfection efficiency. Both the targeting and
      nontargeting nanocarriers were effective for transferring siRNA in vitro. The
      cellular uptake and distribution of nanoparticles complexed with siRNA was
      analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the
      gastric cancer-targeting effect was verified in vivo by MRI and histology
      analysis. These results indicate that scFv(CD44v6)-PEG-g-PEI-SPION is a promising
      nonviral vector for gastric cancer gene therapy and diagnosis.

PMID- 22848159
TI  - Nanocalcium-deficient hydroxyapatite-poly (e-caprolactone)-polyethylene glycol
      poly (e-caprolactone) composite scaffolds.
AB  - A bioactive composite of nano calcium-deficient apatite (n-CDAP) with an atom
      molar ratio of calcium to phosphate (Ca/P) of 1.50 and poly(E-caprolactone)
      poly(ethylene glycol)-poly(E-caprolactone) (PCL-PEG-PCL) was synthesized, and a
      composite scaffold was fabricated. The composite scaffolds with 40 wt% n-CDAP
      contained well interconnected macropores around 400 MUm, and exhibited a porosity
      of 75%. The weight-loss ratio of the n-CDAP/PCL-PEG-PCL was significantly greater
      than nano hydroxyapatite (n-HA, Ca/P = 1.67)/PCL-PEG-PCL composite scaffolds
      during soaking into phosphate-buffered saline (pH 7.4) for 70 days, indicating
      that n-CDAP-based composite had good degradability compared with n-HA. The
      viability ratio of MG-63 cells was significantly higher on n-CDAP than n-HA-based
      composite scaffolds at 3 and 5 days. In addition, the alkaline phosphatase
      activity of the MG-63 cells cultured on n-CDAP was higher than n-HA-based
      composite scaffolds at 7 days. Histological evaluation showed that the
      introduction of n-CDAP into PCL-PEG-PCL enhanced the efficiency of new bone
      formation when the composite scaffolds were implanted into rabbit bone defects.
      The results suggested that the n-CDAP-based composite exhibits good
      biocompatibility, biodegradation, and osteogenesis in vivo.

PMID- 22848161
TI  - Influences of surface coatings and components of FePt nanoparticles on the
      suppression of glioma cell proliferation.
AB  - Malignant gliomas are primary brain tumors with high rates of morbidity and
      mortality; they are the fourth most common cause of cancer death. Novel
      diagnostic and therapeutic techniques based on nanomaterials provide promising
      options in the treatment of malignant gliomas. In order to evaluate the potential
      of FePt nanoparticles (NPs) for malignant glioma therapy, FePt NPs with different
      surface coatings and components were tunably synthesized using oleic
      acid/oleylamine (OA/OA) and cysteines (Cys) as the capping agents, respectively.
      The samples were characterized using X-ray diffraction, transmission electron
      microscopy (TEM), X-ray photon spectroscopy, Fourier transform infrared
      spectroscopy, atomic absorption spectrum, and zeta potential. The influence of
      the surface coatings and components of the FePt NPs on the proliferation of
      glioma cells was assessed through MTT assay and TEM observation using three
      typical glioma cell lines (glioma U251 cells, astrocytoma U87 cells, and
      neuroglioma H4 cells) as in vitro models. The results showed that the
      proliferation of glioma cells was significantly suppressed by lipophilic FePt
      OA/OA NPs in a time- and/or dose-dependent manner, while no or low cytotoxic
      effects were detected in the case of hydrophilic FePt-Cys NPs. The IC50 value of
      FePt-OA/OA NPs on the three glioma cell lines was approximately 5-10 MUg mL-1
      after 24 hours' incubation. Although the cellular uptake of FePt NPs was
      confirmed regardless of the surface coatings and components of the FePt NPs, the
      suppression of FePt NPs on glioma cell proliferation was dominantly determined by
      their surface coatings rather than their components. Therefore, these results
      demonstrate that, through engineering of the surface coating, FePt NPs can
      potentially be developed as novel therapeutic agents for malignant gliomas.

PMID- 22848160
TI  - Neurological disorders and therapeutics targeted to surmount the blood-brain
      barrier.
AB  - We are now in an aging population, so neurological disorders, particularly the
      neurodegenerative diseases, are becoming more prevalent in society. As per the
      epidemiological studies, Europe alone suffers 35% of the burden, indicating an
      alarming rate of disease progression. Further, treatment for these disorders is a
      challenging area due to the presence of the tightly regulated blood-brain barrier
      and its unique ability to protect the brain from xenobiotics. Conventional
      therapeutics, although effective, remain critically below levels of optimum
      therapeutic efficacy. Hence, methods to overcome the blood-brain barrier are
      currently a focus of research. Nanotechnological applications are gaining
      paramount importance in addressing this question, and yielding some promising
      results. This review addresses the pathophysiology of the more common
      neurological disorders and novel drug candidates, along with targeted
      nanoparticle applications for brain delivery.

PMID- 22848162
TI  - Solid lipid nanoparticles modified with stearic acid-octaarginine for oral
      administration of insulin.
AB  - The aim of this study was to design and characterize solid lipid nanoparticles
      (SLNs) modified with stearic acid-octaarginine (SA-R8) as carriers for oral
      administration of insulin (SA-R8-Ins-SLNs). The SLNs were prepared by spontaneous
      emulsion solvent diffusion methods. The mean particle size, zeta potential, drug
      loading, and encapsulation efficiency of the SA-R8-Ins-SLNs were 162 nm, 29.87
      mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed
      dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA
      R8. Morphological studies of SA-R8-Ins-SLNs using transmission electron
      microscopy showed that they were spherical. In vitro, a degradation experiment by
      enzymes showed that SLNs and SA-R8 could partially protect insulin from
      proteolysis. Compared to the insulin solution, the SA-R8-Ins-SLNs increased the
      Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a
      significant hypoglycemic effect in diabetic rats over controls was obtained, with
      a SA-R8-Ins-SLN pharmacological availability value of 13.86 +/- 0.79. These
      results demonstrate that SA-R8-modified SLNs promote the oral absorption of
      insulin.

PMID- 22848163
TI  - Engineered hepatitis B virus surface antigen L protein particles for in vivo
      active targeting of splenic dendritic cells.
AB  - Dendritic cells (DCs) are key regulators of adaptive T-cell responses. By
      capturing exogenous antigens and presenting antigen-derived peptides via major
      histocompatibility complex molecules to naive T cells, DCs induce antigen
      specific immune responses in vivo. In order to induce effective host immune
      responses, active delivery of exogenous antigens to DCs is considered important
      for future vaccine development. We recently generated bionanocapsules (BNCs)
      consisting of hepatitis B virus surface antigens that mediate stringent in vivo
      cell targeting and efficient endosomal escape, and after the fusion with
      liposomes (LP) containing therapeutic materials, the BNC-LP complexes deliver
      them to human liver-derived tissues in vivo. BNCs were further modified to
      present the immunoglobulin G (IgG) Fc-interacting domain (Z domain) derived from
      Staphylococcus aureus protein A in tandem. When mixed with IgGs, modified BNCs
      (ZZ-BNCs) displayed the IgG Fv regions outwardly for efficient binding to
      antigens in an oriented-immobilization manner. Due to the affinity of the
      displayed IgGs, the IgG-ZZ-BNC complexes accumulated in specific cells and
      tissues in vitro and in vivo. After mixing ZZ-BNCs with antibodies against DCs,
      we used immunocytochemistry to examine which antibodies delivered ZZ-BNCs to
      mouse splenic DCs following intravenous injection of the ZZ-BNCs. ZZ-BNCs
      displaying anti-CD11c monoclonal antibodies (alpha-CD11c-ZZ-BNCs) were found to
      accumulate with approximately 62% of splenic DCs, and reside within some of them.
      After the fusion with liposomes containing antigens, the alpha-CD11c-ZZ-BNCs
      could elicit the respective antibodies more efficiently than other nontargeting
      control vaccines, suggesting that this DC-specific nanocarrier is promising for
      future vaccines.

PMID- 22848164
TI  - Controlled-release formulation of antihistamine based on cetirizine zinc-layered
      hydroxide nanocomposites and its effect on histamine release from basophilic
      leukemia (RBL-2H3) cells.
AB  - A controlled-release formulation of an antihistamine, cetirizine, was synthesized
      using zinc-layered hydroxide as the host and cetirizine as the guest. The
      resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN,"
      had a basal spacing of 33.9 A, averaged from six harmonics observed from X-ray
      diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between
      the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform
      infrared spectroscopy studies indicated that the intercalation takes place
      without major change in the structure of the guest and that the thermal stability
      of the guest in the nanocomposites is markedly enhanced. The loading of the guest
      in the nanocomposites was estimated to be about 49.4% (w/w). The release study
      showed that about 96% of the guest could be released in 80 hours by phosphate
      buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was
      found that release was governed by pseudo-second order kinetics. Release of
      histamine from rat basophilic leukemia cells was found to be more sensitive to
      the intercalated cetirizine in the CETN compared with its free counterpart, with
      inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay
      toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670
      MUg/mL, respectively.

PMID- 22848165
TI  - Magnetic responsive hydroxyapatite composite scaffolds construction for bone
      defect reparation.
AB  - INTRODUCTION: In recent years, interest in magnetic biomimetic scaffolds for
      tissue engineering has increased considerably. A type of magnetic scaffold
      composed of magnetic nanoparticles (MNPs) and hydroxyapatite (HA) for bone repair
      has been developed by our research group. AIM AND METHODS: In this study, to
      investigate the influence of the MNP content (in the scaffolds) on the cell
      behaviors and the interactions between the magnetic scaffold and the exterior
      magnetic field, a series of MNP-HA magnetic scaffolds with different MNP contents
      (from 0.2% to 2%) were fabricated by immersing HA scaffold into MNP colloid. ROS
      17/2.8 and MC3T3-E1 cells were cultured on the scaffolds in vitro, with and
      without an exterior magnetic field, respectively. The cell adhesion,
      proliferation and differentiation were evaluated via scanning electron
      microscopy; confocal laser scanning microscopy; and 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase, and bone gla protein
      activity tests. RESULTS: The results demonstrated the positive influence of the
      magnetic scaffolds on cell adhesion, proliferation, and differentiation. Further,
      a higher amount of MNPs on the magnetic scaffolds led to more significant
      stimulation. CONCLUSION: The magnetic scaffold can respond to the exterior
      magnetic field and engender some synergistic effect to intensify the stimulating
      effect of a magnetic field to the proliferation and differentiation of cells.

PMID- 22848166
TI  - Facile hydrothermal preparation of titanium dioxide decorated reduced graphene
      oxide nanocomposite.
AB  - A simple single-stage approach, based on the hydrothermal technique, has been
      introduced to synthesize reduced graphene oxide/titanium dioxide nanocomposites.
      The titanium dioxide nanoparticles are formed at the same time as the graphene
      oxide is reduced to graphene. The triethanolamine used in the process has two
      roles. It acts as a reducing agent for the graphene oxide as well as a capping
      agent, allowing the formation of titanium dioxide nanoparticles with a narrow
      size distribution (~20 nm). Transmission electron micrographs show that the
      nanoparticles are uniformly distributed on the reduced graphene oxide nanosheet.
      Thermogravimetric analysis shows the nanocomposites have an enhanced thermal
      stability over the original components. The potential applications for this
      technology were demonstrated by the use of a reduced graphene oxide/titanium
      dioxide nanocomposite-modified glassy carbon electrode, which enhanced the
      electrochemical performance compared to a conventional glassy carbon electrode
      when interacting with mercury(II) ions in potassium chloride electrolyte.

PMID- 22848167
TI  - A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity
      and biodistribution.
AB  - PURPOSE: A lipid-based, nanomicelle-loaded docetaxel (M-DOC) was designed and
      characterized. Optical imaging was employed to evaluate the pharmacokinetics and
      antitumor efficacy of docetaxel in vivo. MATERIALS AND METHODS: The M-DOC was
      prepared using the emulsion-diffusion method. Transmission electron microscopy
      and dynamic light scattering were used to assess the morphology and particle size
      of the M-DOC. Critical micelle concentrations, their stability under
      physiological conditions, and their encapsulation efficiency - as measured by
      high-performance liquid chromatography - were assessed. Pharmacological features
      were evaluated in two different animal models by comparing M-DOC treatments with
      docetaxel injections (I-DOC). Bioluminescence imaging was used to assess
      antitumor activity and docetaxel distribution in vivo, using nude mice injected
      with luciferase-expressing MDA-MB-231 human breast tumor cells. In addition,
      animals injected with B16 melanoma cells were used to measure survival time and
      docetaxel distribution. RESULTS: The M-DOC was prepared as round, uniform spheres
      with an effective diameter of 20.8 nm. The critical micelle concentration of the
      original emulsion was 0.06%. Satisfactory encapsulation efficiency (87.6% +/-
      3.0%) and 12-hour stability were achieved. Xenograft results demonstrated that
      the M-DOC was more effective in inhibiting tumor growth, without significantly
      changing body weight. Survival was prolonged by 12.6% in the M-DOC group. Tumor
      growth inhibitory rates in the M-DOC and I-DOC groups were 91.2% and 57.8% in
      volume and 71.8% and 44.9% in weight, respectively. Optical bioluminescence
      imaging of tumor growths yielded similar results. Area under the curve((0-6
      hour)) levels of docetaxel in blood and tumors were significantly higher in the M
      DOC group (15.9 +/- 3.2 MUg/mL(-1), 601.1 +/- 194.5 MUg/g(-1)) than in the I-DOC
      group (7.2 +/- 1.7 MUg/mL(-1), 357.8 +/- 86.2 MUg/g(-1)). The fluorescent dye 1,1
      dioctadecyl-3,3,3,3'-tetramethylindotricarbocyanine iodide mimicked M-DOC in
      optical imaging, and accumulated more in tumors in comparison with I-DOC.
      CONCLUSION: These results suggest that the lipid-based nanomicelle system was
      effective in inhibiting tumor growth, with little toxicity. Moreover, we have
      developed a noninvasive optical imaging method for antitumor drug evaluation,
      which merits further analysis for potential clinical applications.

PMID- 22848168
TI  - Intracellular delivery mechanism and brain delivery kinetics of biodegradable
      cationic bovine serum albumin-conjugated polymersomes.
AB  - BACKGROUND: A novel brain drug delivery system using cationic bovine serum
      albumin (CBSA)-conjugated biodegradable polymersomes (CBSA-PO) was prepared, and
      its intracellular delivery mechanism and brain delivery kinetics were evaluated.
      METHODS AND RESULTS: Biodegradable poly(ethylene glycol)-poly(E-caprolactone)
      (PEG-PCL) was used to prepare the polymersomes, and thiolated CBSA was conjugated
      with the surface of the polymersome. Transmission electron microscopy and dynamic
      light scattering showed that the CBSA-PO had a round and vesicle-like shape, with
      a mean diameter of around 100 nm. Coupling of CBSA with polymersomes was
      confirmed by X-ray photoelectron spectroscopy. Uptake of CBSA-PO by bEnd.3 cells
      was significantly higher than that of unconjugated polymersomes, but was
      inhibited by low temperature, free CBSA, and poly-L-lysine, indicating that
      endocytosis was energy-driven and absorptive-mediated. Cell viability assays
      confirmed the good safety profile of biodegradable CBSA-PO. Pharmacokinetic
      results demonstrated that the polymersomes had long circulation times, and CBSA
      conjugation on the polymersomes significantly increased the blood-brain barrier
      permeability surface area product by 3.6-fold and the percentage of injected dose
      per gram brain (% ID/g brain) by 2.1-fold. Capillary depletion experiments showed
      that CBSA-PO was distributed into the brain parenchyma in a time-dependent
      manner, with few polymersomes detected, indicating that conjugation of
      polymersomes with CBSA significantly improved their transcytosis across the brain
      blood barrier. CONCLUSION: These results suggest that CBSA-PO is a promising drug
      brain delivery carrier with low toxicity.

PMID- 22848169
TI  - Self-illuminating quantum dots for highly sensitive in vivo real-time luminescent
      mapping of sentinel lymph nodes.
AB  - Quantum dots (QDs) show promise as novel nanomaterials for sentinel lymph node
      (SLN) mapping through their use in noninvasive in vivo fluorescence imaging, and
      they have provided remarkable results. However, in vivo fluorescence imaging has
      limitations mainly reflected in the strong autofluorescence and low deepness of
      tissue penetration associated with this technique. Here, we report on the use of
      self-illuminating 3-mercaptopropionic acid-capped CdTe/CdS QDs for mouse axillary
      SLN mapping by bioluminescence resonance energy transfer, which was found to
      overcome these limitations [corrected]. We used CdTe/CdS QDs synthesized in
      aqueous solution to conjugate a mutant of the bioluminescent protein, Renilla
      reniformis luciferase. The nanobioconjugates obtained had an average hydrodynamic
      diameter of 19 nm, and their luminescence catalyzed by the substrate
      (coelenterazine) could penetrate into at least 20 mm of hairless pigskin, which
      could be observed using an in vivo imaging system equipped with a 700 nm emission
      filter. Conversely, the fluorescence of the nanobioconjugates penetrated no more
      than 10 mm of pigskin and was observed with a strong background. When 80 MUL of
      the nanobioconjugates (containing about 0.5 MUmol/L of QDs) and 5 MUL of
      coelenterazine (1 MUg/MUL) were intradermally injected into a mouse paw, the
      axillary SLN could be imaged in real time without external excitation, and little
      background interference was detected. Furthermore, the decayed luminescence of QD
      Luc8 in SLNs could be recovered after being intradermally reinjected with the
      coelenterazine. Our data showed that using self-illuminating QDs, as opposed to
      fluorescence QDs, has greatly enhanced sensitivity in SLN mapping, and that the
      SLN could be identified synchronously by the luminescence and fluorescence of the
      self-illuminating QDs.

PMID- 22848171
TI  - Influence of microenvironment on cell adhesion, polarization, and migration.

PMID- 22848170
TI  - Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug
      carriers.
AB  - A targeted drug delivery system is the need of the hour. Guiding magnetic iron
      oxide nanoparticles with the help of an external magnetic field to its target is
      the principle behind the development of superparamagnetic iron oxide
      nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small
      synthetic gamma-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core
      ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated
      with certain biocompatible polymers, such as dextran or polyethylene glycol,
      which provide chemical handles for the conjugation of therapeutic agents and also
      improve their blood distribution profile. The current research on SPIONs is
      opening up wide horizons for their use as diagnostic agents in magnetic resonance
      imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by
      coupling with functionalized SPIONs to their targeted site is one of the most
      pursued areas of research in the development of cancer treatment strategies.
      SPIONs have also demonstrated their efficiency as nonviral gene vectors that
      facilitate the introduction of plasmids into the nucleus at rates multifold those
      of routinely available standard technologies. SPION-induced hyperthermia has also
      been utilized for localized killing of cancerous cells. Despite their potential
      biomedical application, alteration in gene expression profiles, disturbance in
      iron homeostasis, oxidative stress, and altered cellular responses are some SPION
      related toxicological aspects which require due consideration. This review
      provides a comprehensive understanding of SPIONs with regard to their method of
      preparation, their utility as drug delivery vehicles, and some concerns which
      need to be resolved before they can be moved from bench top to bedside.

PMID- 22848172
TI  - Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells.
AB  - BACKGROUND: The neurotrophic receptor tyrosine kinase B (TrkB) has diverse
      signaling roles in neurons and tumor cells. Accordingly, its suppressive
      targeting is of interest in neuroblastoma and other tumors, whereas its role in
      improving survival is focused in neurons. Here we describe targeting of TrkB
      binding peptide-conjugated liposomes (PCL) to the TrkB-expressing mouse
      macrophage-like cell line RAW264, and to all-trans-retinoic acid-treated neuron
      like TrkB+ SH-SY5Y human neuroblastoma cells. METHODS: Binding and
      internalization of PCL was monitored by flow cytometry and confocal fluorescence
      microscopy. RESULTS: Internalization of TrkB-targeted PCL by RAW264 cells was
      enhanced and faster when compared with PCL having the corresponding scrambled
      peptide. Likewise, binding and augmented uptake were confirmed for TrkB+ SH-SY5Y
      cells, with targeted PCL appearing in the cytoplasm after 20 minutes of
      incubation. CONCLUSION: We demonstrate here the feasibility of targeting
      liposomes to TrkB-expressing cells by 18-mer peptides, promoting cellular uptake
      (at least partly into endosomes) via receptor-mediated pathways.

PMID- 22848173
TI  - Antitumor activity of folate-targeted, paclitaxel-loaded polymeric micelles on a
      human esophageal EC9706 cancer cell line.
AB  - BACKGROUND: Esophageal cancer is recognized as one of the most refractory
      pernicious diseases. In addition, it is an aggressive malignancy with a
      propensity for local progression and distant dissemination. Because of the poor
      long-term prognosis for patients with esophageal cancer, increasing attention has
      focused on the integration of targeted agents into current therapeutics.
      Nevertheless, there have been few studies reported concerning the therapeutic
      efficacy of paclitaxel-conjugated polymeric micelles in human esophageal cancer
      in vivo. Therefore, the aim of this research was to investigate the tumor
      inhibition effect of composite micelles containing folic acid and paclitaxel on
      the human esophageal EC9706 cancer cell line. METHODS AND RESULTS: Intravenous
      administration of folate-targeted, paclitaxel-loaded micelles was demonstrated to
      be more efficient in inhibiting subcutaneous xenograft tumors and extending the
      survival rate of tumor-bearing nude mice than free paclitaxel and plain
      paclitaxel micelles at an equivalent paclitaxel dose of 20 mg/kg, which was
      further backed up by flow cytometry, TUNEL, and expression of apoptosis-related
      proteins, including Bax, Bcl2, and caspase 3 in this study. CONCLUSION: The
      folate-mediated paclitaxel-loaded polymeric micelle is a promising agent for the
      treatment of human esophageal cancer.

PMID- 22848175
TI  - Oleanolic acid liposomes with polyethylene glycol modification: promising
      antitumor drug delivery.
AB  - BACKGROUND: Oleanolic acid is a pentacyclic triterpene present in many fruits and
      vegetables, and has received much attention on account of its biological
      properties. However, its poor solubility and low bioavailability limit its use.
      The objective of this study was to encapsulate oleanolic acid into nanoliposomes
      using the modified ethanol injection method. METHODS: The liposomes contain a
      hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a
      protective hydrophilic polyethylene glycol (PEG) coating. During the preparation
      process, the formulations described were investigated by designing 34 orthogonal
      experiments as well as considering the effects of different physical
      characteristics. The four factors were the ratios of drug to soybean
      phosphatidylcholine (w/w), cholesterol (w/w), PEG-2000 (w/w), and temperature of
      phosphate-buffered saline at three different levels. We identified the optimized
      formulation which showed the most satisfactory lipid stability and particle
      formation. The morphology of the liposomes obtained was determined by
      transmission electron microscopy and atomic force microscopy. The existence of
      PEG in the liposome component was validated by Fourier transform infrared
      spectrum analysis. RESULTS: The PEGylated liposomes dispersed individually and
      had diameters of around 110-200 nm. Encapsulation efficiency was more than 85%,
      as calculated by high-performance liquid chromatography and Sephadex(r) gel
      filtration. Furthermore, when compared with native oleanolic acid, the liposomal
      formulations showed better stability in vitro. Finally, the cytotoxicity of the
      oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay.
      CONCLUSION: These results suggest that PEGylated liposomes would serve as a
      potent delivery vehicle for oleanolic acid in future cancer therapy.

PMID- 22848176
TI  - Size-dependent antimicrobial properties of CuO nanoparticles against Gram
      positive and -negative bacterial strains.
AB  - BACKGROUND: CuO is one of the most important transition metal oxides due to its
      captivating properties. It is used in various technological applications such as
      high critical temperature superconductors, gas sensors, in photoconductive
      applications, and so on. Recently, it has been used as an antimicrobial agent
      against various bacterial species. Here we synthesized different sized CuO
      nanoparticles and explored the size-dependent antibacterial activity of each CuO
      nanoparticles preparation. METHODS: CuO nanoparticles were synthesized using a
      gel combustion method. In this approach, cupric nitrate trihydrate and citric
      acid were dissolved in distilled water with a molar ratio of 1:1. The resulting
      solution was stirred at 100 degrees C, until gel was formed. The gel was allowed
      to burn at 200 degrees C to obtain amorphous powder, which was further annealed
      at different temperatures to obtain different size CuO nanoparticles. We then
      tested the antibacterial properties using well diffusion, minimum inhibitory
      concentration, and minimum bactericidal concentration methods. RESULTS: XRD
      spectra confirmed the formation of single phase CuO nanoparticles. Crystallite
      size was found to increase with an increase in annealing temperature due to
      atomic diffusion. A minimum crystallite size of 20 nm was observed in the case of
      CuO nanoparticles annealed at 400 degrees C. Transmission electron microscopy
      results corroborate well with XRD results. All CuO nanoparticles exhibited
      inhibitory effects against both Gram-positive and -negative bacteria. The size of
      the particles was correlated with its antibacterial activity. CONCLUSION: The
      antibacterial activity of CuO nanoparticles was found to be size-dependent. In
      addition, the highly stable minimum-sized monodispersed copper oxide
      nanoparticles synthesized during this study demonstrated a significant increase
      in antibacterial activities against both Gram-positive and -negative bacterial
      strains.

PMID- 22848174
TI  - Cellular interaction of folic acid conjugated superparamagnetic iron oxide
      nanoparticles and its use as contrast agent for targeted magnetic imaging of
      tumor cells.
AB  - The purpose of the study was to develop tumor specific, water dispersible
      superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy
      as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs
      capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water
      dispersible, biocompatible having narrow range of size dispersity (8-10 nm), and
      relatively high T2 relaxivity (R2 = 222L . mmol-1 . sec-1). The targeting
      efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was
      evaluated in a folic acid receptor overexpressing and negative tumor cell lines.
      Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher
      intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs
      were seen as clustered inside the various stages of endocytic pathways without
      damaging cellular organelles and possible mechanism for their entry is via
      receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better
      T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess
      high colloidal stability with excellent sensitivity of imaging and can be a
      useful MRI contrast agent for the detection of cancer.

PMID- 22848177
TI  - Enhanced oral bioavailability of docetaxel by lecithin nanoparticles:
      preparation, in vitro, and in vivo evaluation.
AB  - The aim of this research work was to investigate the potential of lecithin
      nanoparticles (LNs) in improving the oral bioavailability of docetaxel. Docetaxel
      loaded LNs (DTX-LNs) were prepared from oil-in-water emulsions and characterized
      in terms of morphology, size, zeta potential, and encapsulation efficiency. The
      in vitro release of docetaxel from the nanoparticles was studied by using
      dialysis bag method. Caco-2 cell monolayer was used for the in vitro permeation
      study of DTX-LNs. Bioavailability studies were conducted in rats and different
      pharmacokinetic parameters were evaluated after oral administration of DTX-LNs.
      The results showed that DTX-LNs had a mean diameter of 360 +/- 8 nm and exhibited
      spherical shape with smooth surface under transmission electron microscopy. The
      DTX-LNs showed a sustained-release profile, with about 80% of docetaxel released
      within 72 hours. The apical to basolateral transport of docetaxel across the Caco
      2 cell monolayer from the DTX-LNs was 2.14 times compared to that of the
      docetaxel solution (0.15 * 10-5 +/- 0.016 * 10-5 cm/second versus 0.07 * 10-5 +/-
      0.003 * 10-5 cm/second). The oral bioavailability of the DTX-LNs was 3.65 times
      that of docetaxel solution (8.75% versus 2.40%). These results indicate that DTX
      LNs were valuable as an oral drug delivery system to enhance the absorption of
      docetaxel.

PMID- 22848179
TI  - Evaluation of the genotoxicity of cellulose nanofibers.
AB  - BACKGROUND: Agricultural products and by products provide the primary materials
      for a variety of technological applications in diverse industrial sectors. Agro
      industrial wastes, such as cotton and curaua fibers, are used to prepare
      nanofibers for use in thermoplastic films, where they are combined with polymeric
      matrices, and in biomedical applications such as tissue engineering, amongst
      other applications. The development of products containing nanofibers offers a
      promising alternative for the use of agricultural products, adding value to the
      chains of production. However, the emergence of new nanotechnological products
      demands that their risks to human health and the environment be evaluated. This
      has resulted in the creation of the new area of nanotoxicology, which addresses
      the toxicological aspects of these materials. PURPOSE AND METHODS: Contributing
      to these developments, the present work involved a genotoxicological study of
      different nanofibers, employing chromosomal aberration and comet assays, as well
      as cytogenetic and molecular analyses, to obtain preliminary information
      concerning nanofiber safety. The methodology consisted of exposure of Allium cepa
      roots, and animal cell cultures (lymphocytes and fibroblasts), to different types
      of nanofibers. Negative controls, without nanofibers present in the medium, were
      used for comparison. RESULTS: The nanofibers induced different responses
      according to the cell type used. In plant cells, the most genotoxic nanofibers
      were those derived from green, white, and brown cotton, and curaua, while
      genotoxicity in animal cells was observed using nanofibers from brown cotton and
      curaua. An important finding was that ruby cotton nanofibers did not cause any
      significant DNA breaks in the cell types employed. CONCLUSION: This work
      demonstrates the feasibility of determining the genotoxic potential of nanofibers
      derived from plant cellulose to obtain information vital both for the future
      usage of these materials in agribusiness and for an understanding of their
      environmental impacts.

PMID- 22848178
TI  - A physical model for the size-dependent cellular uptake of nanoparticles modified
      with cationic surfactants.
AB  - BACKGROUND: The aim of this work was to improve oral bioavailability. The uptake
      of a series of quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB)
      modified nanoparticles (with uniform sizes ranging from 50 nm to 300 nm) into
      heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) and human
      colon adenocarcinoma cells (HT-29) was investigated. METHODS: Coumarin-6 (C6)
      loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared with DMAB
      using the emulsion solvent diffusion method. The physicochemical properties and
      cellular uptake of these nanoparticles were studied. Deserno's model was applied
      to explain the experimental observations. RESULTS: The results showed that the
      surface modification of PLGA nanoparticles with DMAB notably improved the
      cellular uptake. The cellular uptake was size-dependent and had an optimal
      particle size of 100 nm. The experimental data was integrated numerically, and
      was in agreement with the theoretical model. CONCLUSION: These results indicated
      that the interactions between the charged nanoparticles and the cells resulted
      from various forces (eg, electrostatic forces, hydrophobic forces, bending and
      stretching forces, and limited receptor-mediated endocytosis), and the uptake of
      the nanoparticles occurred as a result of competition.

PMID- 22848180
TI  - Study on antibacterial alginate-stabilized copper nanoparticles by FT-IR and 2D
      IR correlation spectroscopy.
AB  - BACKGROUND: The objective of this study was to clarify the intermolecular
      interaction between antibacterial copper nanoparticles (Cu NPs) and sodium
      alginate (NaAlg) by Fourier transform infrared spectroscopy (FT-IR) and to
      process the spectra applying two-dimensional infrared (2D-IR) correlation
      analysis. To our knowledge, the addition of NaAlg as a stabilizer of copper
      nanoparticles has not been previously reported. It is expected that the obtained
      results will provide valuable additional information on: (1) the influence of
      reducing agent ratio on the formation of copper nanoparticles in order to design
      functional nanomaterials with increased antibacterial activity, and (2)
      structural changes related to the incorporation of Cu NPs into the polymer
      matrix. METHODS: Cu NPs were prepared by microwave heating using ascorbic acid as
      reducing agent and NaAlg as stabilizing agent. The characterization of
      synthesized Cu NPs by ultraviolet visible spectroscopy, transmission electron
      microscopy (TEM), electron diffraction analysis, X-ray diffraction (XRD), and
      semiquantitative analysis of the weight percentage composition indicated that the
      average particle sizes of Cu NPs are about 3-10 nm, they are spherical in shape,
      and consist of zerovalent Cu and Cu2O. Also, crystallite size and relative
      particle size of stabilized Cu NPs were calculated by XRD using Scherrer's
      formula and FT from the X-ray diffraction data. Thermogravimetric analysis,
      differential thermal analysis, differential scanning calorimetry (DSC), FT-IR,
      second-derivative spectra, and 2D-IR correlation analysis were applied to
      studying the stabilization mechanism of Cu NPs by NaAlg molecules. The minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of
      stabilized Cu NPs against five bacterial strains (Staphylococccus aureus ATCC
      6538P, Escherichia coli ATCC 25922 and O157: H7, and Salmonella enterica serovar
      Typhimurium ATCC 13311 and 14028) were evaluated with macrodilution, agar
      dilution plate count, and well-diffusion methods. RESULTS: On the basis of the
      semiquantitative analysis, there was a direct correlation between the reducing
      agent ratio and the percentage of zerovalent Cu. This was confirmed with the
      statistical analysis of population of Cu NPs from TEM micrographs. At lower
      reducing agent ratios, two phases coexist (Cu2O and zerovalent Cu) due to
      incomplete reduction of copper ions by the reducing agent; however, at higher
      reducing agent ratios, the Cu NPs consist mainly of zerovalent Cu. Crystallite
      size and relative particle size of stabilized Cu NPs showed considerable
      differences in results and tendencies in respect to TEM analysis. However, the
      relative particle size values obtained from FT of XRD data agreed well with the
      histograms from the TEM observations. From FT results, the relative particle size
      and reducing agent ratio of stabilized Cu NPs showed an inverse correlation. The
      incomplete reduction of copper ions at lower reducing agent ratios was also
      confirmed by DSC studies. FT-IR and 2D-IR correlation spectra analysis suggested
      the first event involved in the stabilization of Cu NPs is their electrostatic
      interaction with -C=O of carboxylate groups of NaAlg, followed by the interaction
      with the available O-C-O-, and finally with the -OH groups. Bacterial
      susceptibility to stabilized nanoparticles was found to vary depending on the
      bacterial strains. The lowest MIC and MBC of stabilized Cu NPs ranged between 2
      mg/L and 8 mg/L for all studied strains. Disk-diffusion studies with both E. coli
      strains revealed greater effectiveness of the stabilized Cu NPs compared to the
      positive controls (cloxacillin, amoxicillin, and nitrofurantoin). S. aureus
      showed the highest sensitivity to stabilized Cu NPs compared to the other studied
      strains. CONCLUSION: Cu NPs were successfully synthesized via chemical reduction
      assisted with microwave heating. Average particle size, polydispersity, and phase
      composition of Cu NPs depended mainly on the reducing agent ratio. Likewise,
      thermal stability and antibacterial activity of stabilized Cu NPs were affected
      by their phase composition. Because of the carboxylate groups in polymer chains,
      the structural changes of stabilized Cu NPs are different from those of NaAlg.
      NaAlg acted as a size controller and stabilizing agent of Cu NPs, due to their
      ability to bind strongly to the metal surface. Our study on the stabilizing agent
      dependent structural changes of stabilized NPs is helpful for wide application of
      NaAlg as an important biopolymer.

PMID- 22848182
TI  - Longitudinal course of deficient emotional self-regulation CBCL profile in youth
      with ADHD: prospective controlled study.
AB  - BACKGROUND: While symptoms of deficient emotional self-regulation (DESR) have
      been long associated with attention-deficit/hyperactivity disorder (ADHD), there
      has been limited investigation of this aspect of the clinical picture of the
      disorder. The main aim of this study was to examine the predictive utility of
      DESR in moderating the course of ADHD children into adolescence. METHODS:
      Subjects comprised 177 children with and 204 children without ADHD followed for
      an average of 4 years (aged 6-18 years at baseline, 54% male). Subjects were
      assessed with structured diagnostic interviews and measures of psychosocial
      functioning. DESR was defined by the presence (n = 79) or absence (n = 98) of
      Child Behavior Checklist (CBCL)-DESR profile (score >= 180 < 210 total of
      Attention, Aggression, and Anxious/Depressed subscales) at the baseline
      assessment. RESULTS: Of subjects with DESR at baseline, 57% had DESR at follow
      up. Persistent ADHD was significantly associated with DESR at follow-up (chi(2)
      ((1)) = 15.37, P < 0.001). At follow-up, ADHD + DESR subjects had significantly
      more comorbidities (z = 2.55, P = 0.01), a higher prevalence of oppositional
      defiant disorder (z = 3.01, P = 0.003), and more impaired CBCL social problems t
      score (t((227)) = 2.41, P = 0.02) versus ADHD subjects. CONCLUSION: This work
      suggests that a positive CBCL-DESR profile predicts subsequent psychopathology
      and functional impairments in children with ADHD suggesting that it has the
      potential to help identify children with ADHD at high risk for compromised
      outcomes.

PMID- 22848181
TI  - Wollastonite nanofiber-doped self-setting calcium phosphate bioactive cement for
      bone tissue regeneration.
AB  - The purpose of this study was to synthesize a self-setting bioactive cement by
      incorporation of wollastonite nanofibers (WNFs) into calcium phosphate cement
      (CPC). The composition, morphology, setting time, compressive strength,
      hydrophilicity, and degradation of WNF-doped CPC (wnf-CPC) were investigated.
      Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray
      diffraction, and inductively coupled plasma atomic emission spectroscopy were
      utilized. Additionally, methyl-thiazolyl-tetrazolium bromide assay, scanning
      electron microscopy, inductively coupled plasma atomic emission spectroscopy, and
      histological evaluation were used to study the cell and tissue responses to wnf
      CPC, both in vitro and in vivo. The results confirmed that the addition of WNFs
      into CPC had no obvious effect on the setting time or the compressive strength of
      wnf-CPC, provided the WNF amount was not more than 10 wt%. However, the
      hydrophilicity and degradability of wnf-CPC were significantly improved by the
      addition of WNFs - this was because of the change of microstructure caused by the
      WNFs. The preferred dissolution of WNFs caused the formation of microporosity in
      wnf-CPC when soaked in tris hydrochloride solution. The microporosity enlarged
      the surface area of the wnf-CPC and so promoted degradation of the wnf-CPC when
      in contact with liquid. In addition, MG-63 cell attachment and proliferation on
      the wnf-CPC were superior to that on the CPC, indicating that incorporation of
      WNFs into CPC improved the biological properties for wnf-CPC. Following the
      implantation of wnf-CPC into bone defects of rabbits, histological evaluation
      showed that wnf-CPC enhanced the efficiency of new bone formation in comparison
      with CPC, indicating excellent biocompatibility and osteogenesis of wnf-CPC. In
      conclusion, wnf-CPC exhibited promising prospects in bone regeneration.

PMID- 22848183
TI  - Copy number variants in a sample of patients with psychotic disorders: is
      standard screening relevant for actual clinical practice?
AB  - With the introduction of new genetic techniques such as genome-wide array
      comparative genomic hybridization, studies on the putative genetic etiology of
      schizophrenia have focused on the detection of copy number variants (CNVs), ie,
      microdeletions and/or microduplications, that are estimated to be present in up
      to 3% of patients with schizophrenia. In this study, out of a sample of 100
      patients with psychotic disorders, 80 were investigated by array for the presence
      of CNVs. The assessment of the severity of psychiatric symptoms was performed
      using standardized instruments and ICD-10 was applied for diagnostic
      classification. In three patients, a submicroscopic CNV was demonstrated, one
      with a loss in 1q21.1 and two with a gain in 1p13.3 and 7q11.2, respectively. The
      association between these or other CNVs and schizophrenia or schizophrenia-like
      psychoses and their clinical implications still remain equivocal. While the CNV
      affected genes may enhance the vulnerability for psychiatric disorders via
      effects on neuronal architecture, these insights have not resulted in major
      changes in clinical practice as yet. Therefore, genome-wide array analysis should
      presently be restricted to those patients in whom psychotic symptoms are paired
      with other signs, particularly dysmorphisms and intellectual impairment.

PMID- 22848184
TI  - Effects of once-daily extended release quetiapine fumarate on patient-reported
      outcomes in patients with generalized anxiety disorder.
AB  - BACKGROUND: We evaluated the effects of once-daily extended-release quetiapine
      fumarate (quetiapine XR) on patient-reported outcomes in generalized anxiety
      disorder (GAD). METHODS: This is a report of a pooled analysis from three acute 8
      week, randomized, placebocontrolled, fixed-dose (50, 150, 300 mg/day) studies and
      a 52-week maintenance flexible dose (50-300 mg/day) study of quetiapine XR
      monotherapy in patients with GAD. Quality of Life Enjoyment and Satisfaction
      Questionnaire Short Form (Q-LES-Q-SF) percent maximum total scores (items 1-14),
      item 15 ("satisfaction with medication"), item 16 ("overall life satisfaction"),
      and Pittsburgh Sleep Quality Index (PSQI) global scores are reported. Sheehan
      Disability Scale (SDS) total scores were also assessed (maintenance study only).
      RESULTS: The acute studies showed significant improvements at week 8 in Q-LES-Q
      SF percent maximum total score with quetiapine XR 150 mg/day (P < 0.001) and item
      16 with quetiapine XR 50 (P < 0.05) and 150 mg/day (P < 0.001) versus placebo;
      PSQI global scores significantly improved with quetiapine XR 50, 150, and 300
      mg/day versus placebo (P < 0.001). The maintenance study showed significant
      benefits versus placebo with quetiapine XR 50-300 mg/day in Q-LES-Q-SF percent
      total score, item 15 and item 16 scores, PSQI global score, and SDS total score.
      CONCLUSION: Quetiapine XR 150 mg/day (acute studies) and 50-300 mg/day
      (maintenance study) improved quality of life, overall functioning, and sleep
      quality in patients with GAD.

PMID- 22848185
TI  - Pattern sensitivity: a missed part of the diagnosis.
AB  - RATIONALE: Pattern sensitivity can be diagnosed by presenting a series of visual
      patterns to the subject in the electroencephalography (EEG) laboratory; however,
      testing for pattern sensitivity is not routinely done during EEG recording. This
      work aimed to highlight the incidence of pattern sensitivity among patients
      referred for routine EEG recording during a 1-year period, identifying the cause
      of referral, diagnosis, and the characteristics of pattern-sensitive patients.
      METHODS: All patients aged 4 years and older who were referred for routine EEG
      during a 12-month period and had no motor or visual impairment were enrolled in
      the study. Intermittent photic stimulation and pattern sensitivity were tested
      for each case. Pattern sensitivity was tested by scanning three different
      rhythmically moving patterns at reading distance with the patient seated in an
      illuminated room. A pattern evoking a paroxysmal response was reintroduced after
      exposure to a blank white card to confirm the findings. RESULTS: Two hundred
      twenty-eight patients were studied; twelve patients (5.26%) had pattern
      sensitivity and their ages ranged from 5 to 12 years. Eight of these patients
      (66.7%) were referred for seizure disorders, two were referred with the diagnosis
      of migraine, one with headache and poor scholastic performance and one with
      recurrent attacks of dizziness for investigation. Seven of the twelve patients
      (58.3%) had a previous EEG done without testing for pattern sensitivity. Five
      patients (41.6%) had positive family history for epilepsy, three (25%) for
      migraine, and two (16.6%) for migraine and epilepsy. Two patients (16.6%) had
      pattern sensitivity without photosensitivity. Pattern stimulation provoked
      epileptiform discharges in eight patients (66.6%), focal discharges in one, and
      unilateral build-up of posterior discharge in three. CONCLUSION: Diagnosis of
      pattern sensitivity is often missed as it is not routinely tested for during EEG
      recording. The result of the study challenges the concept of a consistent
      association between photosensitivity and pattern sensitivity; it also raises
      questions about the incidence of pattern sensitivity among children who do not
      suffer from epilepsy and in particular those with migraine, headache and
      scholastic difficulties. Further studies are therefore needed to clarify the
      phenotypic spectrum of this EEG trait.

PMID- 22848187
TI  - Regression calibration with heteroscedastic error variance.
AB  - The problem of covariate measurement error with heteroscedastic measurement error
      variance is considered. Standard regression calibration assumes that the
      measurement error has a homoscedastic measurement error variance. An estimator is
      proposed to correct regression coefficients for covariate measurement error with
      heteroscedastic variance. Point and interval estimates are derived. Validation
      data containing the gold standard must be available. This estimator is a closed
      form correction of the uncorrected primary regression coefficients, which may be
      of logistic or Cox proportional hazards model form, and is closely related to the
      version of regression calibration developed by Rosner et al. (1990). The primary
      regression model can include multiple covariates measured without error. The use
      of these estimators is illustrated in two data sets, one taken from occupational
      epidemiology (the ACE study) and one taken from nutritional epidemiology (the
      Nurses' Health Study). In both cases, although there was evidence of moderate
      heteroscedasticity, there was little difference in estimation or inference using
      this new procedure compared to standard regression calibration. It is shown
      theoretically that unless the relative risk is large or measurement error severe,
      standard regression calibration approximations will typically be adequate, even
      with moderate heteroscedasticity in the measurement error model variance. In a
      detailed simulation study, standard regression calibration performed either as
      well as or better than the new estimator. When the disease is rare and the errors
      normally distributed, or when measurement error is moderate, standard regression
      calibration remains the method of choice.

PMID- 22848188
TI  - A tutorial on methods to estimating clinically and policy-meaningful measures of
      treatment effects in prospective observational studies: a review.
AB  - In randomized controlled trials (RCTs), treatment assignment is unconfounded with
      baseline covariates, allowing outcomes to be directly compared between treatment
      arms. When outcomes are binary, the effect of treatment can be summarized using
      relative risks, absolute risk reductions and the number needed to treat (NNT).
      When outcomes are time-to-event in nature, the effect of treatment on the
      absolute reduction of the risk of an event occurring within a specified duration
      of follow-up and the associated NNT can be estimated. In observational studies of
      the effect of treatments on health outcomes, treatment is frequently confounded
      with baseline covariates. Regression adjustment is commonly used to estimate the
      adjusted effect of treatment on outcomes. We highlight several limitations of
      measures of treatment effect that are directly obtained from regression models.
      We illustrate how both regression-based approaches and propensity-score based
      approaches allow one to estimate the same measures of treatment effect as those
      that are commonly reported in RCTs. The CONSORT statement recommends that both
      relative and absolute measures of treatment effects be reported for RCTs with
      dichotomous outcomes. The methods described in this paper will allow for similar
      reporting in observational studies.

PMID- 22848190
TI  - Fitting a bivariate measurement error model for episodically consumed dietary
      components.
AB  - There has been great public health interest in estimating usual, i.e., long-term
      average, intake of episodically consumed dietary components that are not consumed
      daily by everyone, e.g., fish, red meat and whole grains. Short-term measurements
      of episodically consumed dietary components have zero-inflated skewed
      distributions. So-called two-part models have been developed for such data in
      order to correct for measurement error due to within-person variation and to
      estimate the distribution of usual intake of the dietary component in the
      univariate case. However, there is arguably much greater public health interest
      in the usual intake of an episodically consumed dietary component adjusted for
      energy (caloric) intake, e.g., ounces of whole grains per 1000 kilo-calories,
      which reflects usual dietary composition and adjusts for different total amounts
      of caloric intake. Because of this public health interest, it is important to
      have models to fit such data, and it is important that the model-fitting methods
      can be applied to all episodically consumed dietary components.We have recently
      developed a nonlinear mixed effects model (Kipnis, et al., 2010), and have fit it
      by maximum likelihood using nonlinear mixed effects programs and methodology (the
      SAS NLMIXED procedure). Maximum likelihood fitting of such a nonlinear mixed
      model is generally slow because of 3-dimensional adaptive Gaussian quadrature,
      and there are times when the programs either fail to converge or converge to
      models with a singular covariance matrix. For these reasons, we develop a Monte
      Carlo (MCMC) computation of fitting this model, which allows for both frequentist
      and Bayesian inference. There are technical challenges to developing this
      solution because one of the covariance matrices in the model is patterned. Our
      main application is to the National Institutes of Health (NIH)-AARP Diet and
      Health Study, where we illustrate our methods for modeling the energy-adjusted
      usual intake of fish and whole grains. We demonstrate numerically that our
      methods lead to increased speed of computation, converge to reasonable solutions,
      and have the flexibility to be used in either a frequentist or a Bayesian manner.

PMID- 22848189
TI  - Simultaneous Bayesian inference for linear, nonlinear and semiparametric mixed
      effects models with skew-normality and measurement errors in covariates.
AB  - In recent years, various mixed-effects models have been suggested for estimating
      viral decay rates in HIV dynamic models for complex longitudinal data. Among
      those models are linear mixed-effects (LME), nonlinear mixed-effects (NLME), and
      semiparametric nonlinear mixed-effects (SNLME) models. However, a critical
      question is whether these models produce coherent estimates of viral decay rates,
      and if not, which model is appropriate and should be used in practice. In
      addition, one often assumes that a model random error is normally distributed,
      but the normality assumption may be unrealistic, particularly if the data exhibit
      skewness. Moreover, some covariates such as CD4 cell count may be often measured
      with substantial errors. This paper addresses these issues simultaneously by
      jointly modeling the response variable with skewness and a covariate process with
      measurement errors using a Bayesian approach to investigate how estimated
      parameters are changed or different under these three models. A real data set
      from an AIDS clinical trial study was used to illustrate the proposed models and
      methods. It was found that there was a significant incongruity in the estimated
      decay rates in viral loads based on the three mixed-effects models, suggesting
      that the decay rates estimated by using Bayesian LME or NLME joint models should
      be interpreted differently from those estimated by using Bayesian SNLME joint
      models. The findings also suggest that the Bayesian SNLME joint model is
      preferred to other models because an arbitrary data truncation is not necessary;
      and it is also shown that the models with a skew-normal distribution and/or
      measurement errors in covariate may achieve reliable results when the data
      exhibit skewness.

PMID- 22848191
TI  - Spatio-temporal activity patterns of odor-induced synchronized potentials
      revealed by voltage-sensitive dye imaging and intracellular recording in the
      antennal lobe of the cockroach.
AB  - In animals, odor qualities are represented as both spatial activity patterns of
      glomeruli and temporal patterns of synchronized oscillatory signals in the
      primary olfactory centers. By optical imaging of a voltage-sensitive dye (VSD)
      and intracellular recording from secondary olfactory interneurons, we examined
      possible neural correlates of the spatial and temporal odor representations in
      the primary olfactory center, the antennal lobe (AL), of the cockroach
      Periplaneta americana. Voltage-sensitive dye imaging revealed that all used
      odorants induced odor-specific temporal patterns of depolarizing potentials in
      specific combinations of anterior glomeruli of the AL. The depolarizing
      potentials evoked by different odorants were temporally synchronized across
      glomeruli and were termed "synchronized potentials." These observations suggest
      that odor qualities are represented by spatio-temporal activity patterns of the
      synchronized potentials across glomeruli. We also performed intracellular
      recordings and stainings from secondary olfactory interneurons, namely projection
      neurons and local interneurons. We analyzed the temporal structures of enanthic
      acid-induced action potentials of secondary olfactory interneurons using
      simultaneous paired intracellular recording from two given neurons. Our results
      indicated that the multiple local interneurons synchronously fired in response to
      the olfactory stimulus. In addition, all stained enanthic acid-responsive
      projection neurons exhibited dendritic arborizations within the glomeruli where
      the synchronized potentials were evoked. Since multiple local interneurons are
      known to synapse to a projection neuron in each glomerulus in the cockroach AL,
      converging inputs from local interneurons to the projection neurons appear to
      contribute the odorant specific spatio-temporal activity patterns of the
      synchronized potentials.

PMID- 22848192
TI  - Decoding the invisible forces of social connections.
AB  - By its 20th anniversary, social neuroscience has witnessed an incredible rise in
      the number of studies demonstrating the effects of perceived social isolation
      (e.g., loneliness, ostracism), and inversely, the beneficial effects of social
      bonding (e.g., love, desire, attachment) on social perception, cognition, and
      behavior and on mental and physical health. The current review underscores the
      importance of two factors in this literature: (1) where an individual falls along
      the continuum of isolation/bonding from feelings of rejection and neglect to
      feelings of strong, stable, trusted social bonds, and (2) whether gauging an
      individual's general feeling of social isolation/bonding or the specific feeling
      of isolation/bonding toward the person with whom the individual is interacting.
      Evidence shows that these factors are related to brain and cognition, including
      embodied social cognition-a system integrating past self-related actions from
      which simulation mechanisms can be used to access other people's minds and
      anticipate their actions. The neurophysiological mechanisms underlying
      sensorimotor mapping between interacting individuals offers an empirical
      opportunity to investigate the interpersonal forces that operate on individuals
      at a distance. This multilevel integrative approach provides a valuable tool for
      investigating the brain networks responsible for understanding acute and chronic
      social disorders.

PMID- 22848193
TI  - Coding of saliency by ensemble bursting in the amygdala of primates.
AB  - Salient parts of a visual scene attract longer and earlier fixations of the eyes.
      Saliency is driven by bottom-up (image dependent) factors and top-down factors
      such as behavioral relevance, goals, and expertise. It is currently assumed that
      a saliency map defining eye fixation priorities is stored in neural structures
      that remain to be determined. Lesion studies support a role for the amygdala in
      detecting saliency. Here we show that neurons in the amygdala of primates fire
      differentially when the eyes approach to or fixate behaviorally relevant parts of
      visual scenes. Ensemble bursting in the amygdala accurately predicts main
      fixations during the free-viewing of natural images. However, fixation prediction
      is significantly better for faces-where a bottom-up computational saliency model
      fails-compared to unfamiliar objects and landscapes. On this basis we propose the
      amygdala as a locus for a saliency map and ensemble bursting as a saliency coding
      mechanism.

PMID- 22848194
TI  - The emerging role of norepinephrine in cognitive dysfunctions of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder,
      affecting 1% of the population over age 60. In those patients cognitive
      dysfunction is a persistent issue that impairs quality of life and productivity.
      Neuropathological studies demonstrate significant damage in brain regions outside
      the nigral dopamine (DA) system, including early degeneration of locus coeruleus
      norepinephrine (LC-NE) neurons, yet discussion of PD and treatment focus has
      remained dopaminergic-based. Motor symptoms benefit from DA replacement for many
      years, but other symptoms including several cognitive deficits continue unabated.
      Recent interest in non-DA substrates of PD highlights early involvement of LC-NE
      neurons and provides evidence for a prodromal phase, with cognitive disturbance,
      even in sporadic PD. We outline insights from basic research in LC-NE function to
      clinical and pathological evidence highlighting a role for NE in PD cognitive
      dysfunction. We propose that loss of LC-NE regulation, particularly in higher
      cortical regions, critically underlies certain cognitive dysfunctions in early
      PD. As a major unmet need for patients, research and use of NE drugs in PD may
      provide significant benefits for cognitive processing.

PMID- 22848195
TI  - Activity in the lateral occipital cortex between 200 and 300 ms distinguishes
      between physically identical seen and unseen stimuli.
AB  - There is converging evidence that electrophysiological responses over posterior
      cortical regions in the 200-300 ms range distinguish between physically identical
      stimuli that reach consciousness or remain unseen. Here, we attempt at
      determining the sources of this awareness-related activity using magneto
      encephalographic (MEG). Fourteen subjects were presented with faint colored
      gratings at threshold for contrast and reported on each trial whether the grating
      was seen or unseen. Subjects were primed with a color cue that could be congruent
      or incongruent with the color of the grating, to probe to what extent two co
      localized features (color and orientation) would be bound in consciousness. The
      contrast between neural responses to seen and unseen physically identical
      gratings revealed a sustained posterior difference between 190 and 350 ms,
      thereby replicating prior studies. We further show that the main sources of the
      awareness-related activity were localized bilaterally on the lateral convexity of
      the occipito-temporal region, in the Lateral Occipital (LO) complex, as well as
      in the right posterior infero-temporal region. No activity differentiating seen
      and unseen trials could be observed in frontal or parietal regions in this
      latency range, even at lower threshold. Color congruency did not improve
      grating's detection, and the awareness-related activity was independent from
      color congruency. However, at the neural level, color congruency was processed
      differently in grating-present and grating-absent trials. The pattern of results
      suggests the existence of a neural process of color congruency engaging left
      parietal regions that is affected by the mere presence of another feature,
      whether this feature reaches consciousness or not. Altogether, our results reveal
      an occipital source of visual awareness insensitive to color congruency, and a
      simultaneous parietal source not engaged in visual awareness, but sensitive to
      the manipulation of co-localized features.

PMID- 22848196
TI  - The hippocampus and exploration: dynamically evolving behavior and neural
      representations.
AB  - We develop a normative statistical approach to exploratory behavior called
      information foraging. Information foraging highlights the specific processes that
      contribute to active, rather than passive, exploration and learning. We
      hypothesize that the hippocampus plays a critical role in active exploration
      through directed information foraging by supporting a set of processes that allow
      an individual to determine where to sample. By examining these processes, we show
      how information directed information foraging provides a formal theoretical
      explanation for the common hippocampal substrates of constructive memory,
      vicarious trial and error behavior, schema-based facilitation of memory
      performance, and memory consolidation.

PMID- 22848197
TI  - Visual and spatial modulation of tactile extinction: behavioural and
      electrophysiological evidence.
AB  - Crossing the hands over the midline reduces left tactile extinction to double
      simultaneous stimulation in right-brain-damaged patients, suggesting that spatial
      attentional biases toward the ipsilesional (right) side of space contribute to
      the patients' contralesional (left) deficit. We investigated (1) whether the
      position of the left hand, and its vision, affected processing speed of tactile
      stimuli, and (2) the electrophysiological underpinnings of the effect of hand
      position. (1) Four right-brain-damaged patients with spatial neglect and
      contralesional left tactile extinction or somatosensory deficits, and eight
      neurologically unimpaired participants, performed a speeded detection task on
      single taps delivered on their left index finger. In patients, placing the left
      hand in the right (heteronymous) hemi-space resulted in faster reaction times
      (RTs) to tactile stimuli, compared to placing that hand in the left (homonymous)
      hemi-space, particularly when the hand was visible. By contrast, in controls
      placing the left hand in the heteronymous hemi-space increased RTs. (2)
      Somatosensory event-related potentials (ERPs) were recorded from one patient and
      two controls in response to the stimulation of the left hand, placed in the two
      spatial positions. In the patient, the somatosensory P70, N140, and N250
      components were enhanced when the left hand was placed in the heteronymous hemi
      space, whereas in controls these components were not modulated by hand position.
      The novel findings are that in patients placing the left hand in the right,
      ipsilesional hemi-space yields a temporal advantage in processing tactile
      stimuli, and this effect may rely on a modulation of stimulus processing taking
      place as early as in the primary somatosensory cortex, as indexed by evoked
      potentials. Furthermore, vision enhances tactile processing specifically when the
      left hand is placed in the hemi-space toward which the patients' attentional
      biases are pathologically directed, namely rightwards.

PMID- 22848198
TI  - When unconscious rewards boost cognitive task performance inefficiently: the role
      of consciousness in integrating value and attainability information.
AB  - Research has shown that high vs. low value rewards improve cognitive task
      performance independent of whether they are perceived consciously or
      unconsciously. However, efficient performance in response to high value rewards
      also depends on whether or not rewards are attainable. This raises the question
      of whether unconscious reward processing enables people to take into account such
      attainability information. Building on a theoretical framework according to which
      conscious reward processing is required to enable higher level cognitive
      processing, the present research tested the hypothesis that conscious but not
      unconscious reward processing enables integration of reward value with
      attainability information. In two behavioral experiments, participants were
      exposed to mask high and low value coins serving as rewards on a working memory
      (WM) task. The likelihood for conscious processing was manipulated by presenting
      the coins relatively briefly (17 ms) or long and clearly visible (300 ms).
      Crucially, rewards were expected to be attainable or unattainable. Requirements
      to integrate reward value with attainability information varied across
      experiments. Results showed that when integration of value and attainability was
      required (Experiment 1), long reward presentation led to efficient performance,
      i.e., selectively improved performance for high value attainable rewards. In
      contrast, in the short presentation condition, performance was increased for high
      value rewards even when these were unattainable. This difference between the
      effects of long and short presentation time disappeared when integration of value
      and attainability information was not required (Experiment 2). Together these
      findings suggest that unconsciously processed reward information is not
      integrated with attainability expectancies, causing inefficient effort
      investment. These findings are discussed in terms of a unique role of
      consciousness in efficient allocation of effort to cognitive control processes.

PMID- 22848199
TI  - Transformation-invariant visual representations in self-organizing spiking neural
      networks.
AB  - The ventral visual pathway achieves object and face recognition by building
      transformation-invariant representations from elementary visual features. In
      previous computer simulation studies with rate-coded neural networks, the
      development of transformation-invariant representations has been demonstrated
      using either of two biologically plausible learning mechanisms, Trace learning
      and Continuous Transformation (CT) learning. However, it has not previously been
      investigated how transformation-invariant representations may be learned in a
      more biologically accurate spiking neural network. A key issue is how the
      synaptic connection strengths in such a spiking network might self-organize
      through Spike-Time Dependent Plasticity (STDP) where the change in synaptic
      strength is dependent on the relative times of the spikes emitted by the
      presynaptic and postsynaptic neurons rather than simply correlated activity
      driving changes in synaptic efficacy. Here we present simulations with
      conductance-based integrate-and-fire (IF) neurons using a STDP learning rule to
      address these gaps in our understanding. It is demonstrated that with the
      appropriate selection of model parameters and training regime, the spiking
      network model can utilize either Trace-like or CT-like learning mechanisms to
      achieve transform-invariant representations.

PMID- 22848200
TI  - Learning view invariant recognition with partially occluded objects.
AB  - This paper investigates how a neural network model of the ventral visual pathway,
      VisNet, can form separate view invariant representations of a number of objects
      seen rotating together. In particular, in the current work one of the rotating
      objects is always partially occluded by the other objects present during
      training. A key challenge for the model is to link together the separate partial
      views of the occluded object into a single view invariant representation of that
      object. We show how this can be achieved by Continuous Transformation (CT)
      learning, which relies on spatial similarity between successive views of each
      object. After training, the network had developed cells in the output layer which
      had learned to respond invariantly to particular objects over most or all views,
      with each cell responding to only one object. All objects, including the
      partially occluded object, were individually represented by a unique subset of
      output cells.

PMID- 22848201
TI  - The interplay of prefrontal and sensorimotor cortices during inhibitory control
      of learned motor behavior.
AB  - In the present study inhibitory cortical mechanisms have been investigated during
      execution and inhibition of learned motor programs by means of multi-channel
      functional near infrared spectroscopy (fNIRS). fNIRS is an emerging non-invasive
      optical technique for the in vivo assessment of cerebral oxygenation, concretely
      changes of oxygenated [oxy-Hb], and deoxygenated [deoxy-Hb] hemoglobin. Eleven
      healthy subjects executed or inhibited previous learned finger and foot movements
      indicated by a visual cue. The execution of finger/foot movements caused a
      typical activation pattern namely an increase of [oxy-Hb] and a decrease of
      [deoxy-Hb] whereas the inhibition of finger/foot movements caused a decrease of
      [oxy-Hb] and an increase of [deoxy-Hb] in the hand or foot representation area
      (left or medial somatosensory and primary motor cortex). Additionally an increase
      of [oxy-Hb] and a decrease of [deoxy-Hb] in the medial area of the anterior
      prefrontal cortex (APFC) during the inhibition of finger/foot movements were
      found. The results showed, that inhibition/execution of learned motor programs
      depends on an interplay of focal increases and decreases of neural activity in
      prefrontal and sensorimotor areas regardless of the effector. As far as we know,
      this is the first study investigating inhibitory processes of finger/foot
      movements by means of multi-channel fNIRS.

PMID- 22848203
TI  - High resolution, high capacity, spatial specificity in perceptual learning.
AB  - Research of perceptual learning has received significant interest due to findings
      that training on perceptual tasks can yield learning effects that are specific to
      the stimulus features of that task. However, recent studies have demonstrated
      that while training a single stimulus at a single location can yield a high
      degree of stimulus specificity, training multiple features, or at multiple
      locations can reveal a broad transfer of learning to untrained features or
      stimulus locations. We devised a high resolution, high capacity, perceptual
      learning procedure with the goal of testing whether spatial specificity can be
      found in cases where observers are highly trained to discriminate stimuli in many
      different locations in the visual field. We found a surprising degree of location
      specific learning, where performance was significantly better when target stimuli
      were presented at 1 of the 24 trained locations compared to when they were placed
      in 1 of the 12 untrained locations. This result is particularly impressive given
      that untrained locations were within a couple degrees of visual angle of those
      that were trained. Given the large number of trained locations, the fact that the
      trained and untrained locations were interspersed, and the high-degree of spatial
      precision of the learning, we suggest that these results are difficult to account
      for using attention or decision strategies and instead suggest that learning may
      have taken place for each location separately in retinotopically organized visual
      cortex.

PMID- 22848202
TI  - Cigarette smoking and brain regulation of energy homeostasis.
AB  - Cigarette smoking is an addictive behavior, and is the primary cause of
      cardiovascular and pulmonary disease, and cancer (among other diseases).
      Cigarette smoke contains thousands of components that may affect caloric intake
      and energy expenditure, although nicotine is the major addictive substance
      present, and has the best described actions. Nicotine exposure from cigarette
      smoke can change brain feeding regulation to reduce appetite via both energy
      homeostatic and reward mechanisms, causing a negative energy state which is
      characterized by reduced energy intake and increased energy expenditure that are
      linked to low body weight. These findings have led to the public perception that
      smoking is associated with weight loss. However, its effects at reducing
      abdominal fat mass (a predisposing factor for glucose intolerance and insulin
      resistance) are marginal, and its promotion of lean body mass loss in animal
      studies suggests a limited potential for treatment in obesity. Smoking during
      pregnancy puts pressure on the mother's metabolic system and is a significant
      contributor to adverse pregnancy outcomes. Smoking is a predictor of future risk
      for respiratory dysfunction, social behavioral problems, cardiovascular disease,
      obesity, and type-2 diabetes. Catch-up growth is normally observed in children
      exposed to intrauterine smoke, which has been linked to subsequent childhood
      obesity. Nicotine can have a profound impact on the developing fetal brain, via
      its ability to rapidly and fully pass the placenta. In animal studies this has
      been linked with abnormal hypothalamic gene expression of appetite regulators
      such as downregulation of NPY and POMC in the arcuate nucleus of the
      hypothalamus. Maternal smoking or nicotine replacement leads to unhealthy eating
      habits (such as junk food addiction) and other behavioral disorders in the
      offspring.

PMID- 22848204
TI  - Inverse MDS: Inferring Dissimilarity Structure from Multiple Item Arrangements.
AB  - The pairwise dissimilarities of a set of items can be intuitively visualized by a
      2D arrangement of the items, in which the distances reflect the dissimilarities.
      Such an arrangement can be obtained by multidimensional scaling (MDS). We propose
      a method for the inverse process: inferring the pairwise dissimilarities from
      multiple 2D arrangements of items. Perceptual dissimilarities are classically
      measured using pairwise dissimilarity judgments. However, alternative methods
      including free sorting and 2D arrangements have previously been proposed. The
      present proposal is novel (a) in that the dissimilarity matrix is estimated by
      "inverse MDS" based on multiple arrangements of item subsets, and (b) in that the
      subsets are designed by an adaptive algorithm that aims to provide optimal
      evidence for the dissimilarity estimates. The subject arranges the items
      (represented as icons on a computer screen) by means of mouse drag-and-drop
      operations. The multi-arrangement method can be construed as a generalization of
      simpler methods: It reduces to pairwise dissimilarity judgments if each
      arrangement contains only two items, and to free sorting if the items are
      categorically arranged into discrete piles. Multi-arrangement combines the
      advantages of these methods. It is efficient (because the subject communicates
      many dissimilarity judgments with each mouse drag), psychologically attractive
      (because dissimilarities are judged in context), and can characterize continuous
      high-dimensional dissimilarity structures. We present two procedures for
      estimating the dissimilarity matrix: a simple weighted-aligned-average of the
      partial dissimilarity matrices and a computationally intensive algorithm, which
      estimates the dissimilarity matrix by iteratively minimizing the error of MDS
      predictions of the subject's arrangements. The Matlab code for interactive
      arrangement and dissimilarity estimation is available from the authors upon
      request.

PMID- 22848205
TI  - Time dependency of psychotherapeutic exchanges: the contribution of the theory of
      dynamic systems in analyzing process.
AB  - This paper provides a general framework for the use of Theory of Dynamic Systems
      (TDS) in the field of psychotherapy research. Psychotherapy is inherently
      dynamic, namely a function of time. Consequently, the improvement of construct
      validity and clinical relevance of psychotherapy process research require the
      development of models of investigation allowing dynamic mappings of clinical
      exchange. Thus, TDS becomes a significant theoretical and methodological
      reference. The paper focuses two topics. First, the main concepts of TDS are
      briefly introduced together with a basic typology of approaches developed within
      this domain. Second, we propose a repertoire of investigation strategies that can
      be used to capture the dynamic nature of clinical exchange. In this way we intend
      to highlight the feasibility and utility of strategies of analysis informed by
      TDS.

PMID- 22848206
TI  - Metabolic Regulation of "Ca. Methylacidiphilum Fumariolicum" SolV Cells Grown
      Under Different Nitrogen and Oxygen Limitations.
AB  - Aerobic methanotrophic bacteria can use methane as their sole energy source. The
      discovery of "Ca. Methylacidiphilum fumariolicum" strain SolV and other
      verrucomicrobial methanotrophs has revealed that the ability of bacteria to
      oxidize CH(4) is much more diverse than has previously been assumed in terms of
      ecology, phylogeny, and physiology. A remarkable characteristic of the methane
      oxidizing Verrucomicrobia is their extremely acidophilic phenotype, growing even
      below pH 1. In this study we used RNA-Seq to analyze the metabolic regulation of
      "Ca. M. fumariolicum" SolV cells growing at MU(max) in batch culture or under
      nitrogen fixing or oxygen limited conditions in chemostats, all at pH 2. The
      analysis showed that two of the three pmoCAB operons each encoding particulate
      methane monoxygenases were differentially expressed, probably regulated by the
      available oxygen. The hydrogen produced during N(2) fixation is apparently
      recycled as demonstrated by the upregulation of the genes encoding a Ni/Fe
      dependent hydrogenase. These hydrogenase genes were also upregulated under low
      oxygen conditions. Handling of nitrosative stress was shown by the expression of
      the nitric oxide reductase encoding genes norB and norC under all conditions
      tested, the upregulation of nitrite reductase nirK under oxygen limitation and of
      hydroxylamine oxidoreductase hao in the presence of ammonium. Unraveling the gene
      regulation of carbon and nitrogen metabolism helps to understand the underlying
      physiological adaptations of strain SolV in view of the harsh conditions of its
      natural ecosystem.

PMID- 22848207
TI  - The Fas/CD95 Receptor Regulates the Death of Autoreactive B Cells and the
      Selection of Antigen-Specific B Cells.
AB  - Cell death receptors have crucial roles in the regulation of immune responses.
      Here we review recent in vivo data confirming that the Fas death receptor
      (TNFSR6) on B cells is important for the regulation of autoimmunity since the
      impairment of only Fas function on B cells results in uncontrolled autoantibody
      production and autoimmunity. Fas plays a role in the elimination of the non
      specific and autoreactive B cells in germinal center, while during the selection
      of antigen-specific B cells different escape signals ensure the resistance to Fas
      mediated apoptosis. Antigen-specific survival such as BCR or MHCII signal or
      coreceptors (CD19) cooperating with BCR inhibits the formation of death inducing
      signaling complex. Antigen-specific survival can be reinforced by antigen
      independent signals of IL-4 or CD40 overproducing the anti-apoptotic members of
      the Bcl-2 family proteins.

PMID- 22848208
TI  - Peroxisome Proliferator Activated Receptor-alpha Agonist Slows the Progression of
      Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory
      Markers in Angiotensin II Infused Mice.
AB  - The anti-inflammatory properties of PPAR-alpha plays an important role in
      attenuating hypertension. The current study determines the anti-hypertensive and
      anti-inflammatory role of PPAR-alpha agonist during a slow-pressor dose of Ang II
      (400 ng/kg/min). Ten to twelve week old male PPAR-alpha KO mice and their WT
      controls were implanted with telemetry devices and infused with Ang II for 12
      days. On day 12 of Ang II infusion, MAP was elevated in PPAR-alpha KO mice
      compared to WT (161 +/- 4 mmHg versus 145 +/- 4 mmHg) and fenofibrate (145
      mg/kg/day) reduced MAP in WT + Ang II mice (134 +/- 7 mmHg). Plasma IL-6 levels
      were higher in PPAR-alpha KO mice on day 12 of Ang II infusion (30 +/- 4 versus 8
      +/- 2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10 +/
      3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J
      expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II
      mice. Our results demonstrate that activation of PPAR-alpha attenuates Ang II
      induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation
      of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of
      ICAM-1 and COX-2.

PMID- 22848210
TI  - Bifidobacterium animalis ssp. lactis 420 Protects against Indomethacin-Induced
      Gastric Permeability in Rats.
AB  - Gastrointestinal (GI) adverse effects such as erosion and increased permeability
      are common during the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Our
      objective was to assess whether Bifidobacterium animalis ssp. lactis 420 protects
      against NSAID-induced GI side effects in a rat model. A total of 120 male Wistar
      rats were allocated into groups designated as control, NSAID, and probiotic. The
      NSAID and probiotic groups were challenged with indomethacin (10 mg/kg(-1);
      single dose). The probiotic group was also supplemented daily with 10(10) CFU of
      B. lactis 420 for seven days prior to the indomethacin administration. The
      control group rats received no indomethacin or probiotic. The permeability of the
      rat intestine was analysed using carbohydrate probes and the visual damage of the
      rat stomach mucosa was graded according to severity. B. lactis 420 significantly
      reduced the indomethacin-induced increase in stomach permeability. However, the
      protective effect on the visual mucosal damage was not significant. The incidence
      of severe NSAID-induced lesions was, nevertheless, reduced from 50% to 33% with
      the probiotic treatment. To conclude, the B. lactis 420 supplementation protected
      the rats from an NSAID-induced increase in stomach permeability and may reduce
      the formation of more serious GI mucosal damage and/or enhance the recovery rate
      of the stomach mucosa.

PMID- 22848211
TI  - Polysaccharides of St. John's Wort Herb Stimulate NHDF Proliferation and NEHK
      Differentiation via Influence on Extracellular Structures and Signal Pathways.
AB  - St. John's Wort herb extracts often contain undesirable or volitional
      polysaccharides. As polysaccharides exhibit structure-dependent biological
      functions in the present study water-soluble polysaccharides were extracted from
      herb material, fractionated by anion exchange chromatography into four main
      polysaccharide fractions (denominated as Hp1, Hp2, Hp3 and Hp4) and characterized
      by HPAEC-PAD, CE, IR and GC-MS. Biological activity on human skin keratinocytes
      and fibroblasts was assessed by investigation of their effect on proliferation,
      metabolism, cytotoxicity, apoptosis and differentiation. The underlying
      mechanisms were investigated in gene expression studies. Polysaccharide fraction
      Hp1 was mainly composed of beta-D-glucose. Hp2, Hp3 and Hp4 contained pectic
      structures and arabinogalactan proteins varying in composition and quantity.
      Polysaccharides of Hp1 induced the keratinocyte differentiation by inhibiting the
      gene expression of the epidermal growth factor and insulin receptor. While the
      collagen secretion of fibroblasts was stimulated by each polysaccharide fraction
      only Hp1 stimulated the synthesis. The fibroblast proliferation was reduced by
      Hp1 and increased by Hp4. This effect was related to the influence on genes that
      referred to oxidative stress, metabolism, transcription processes and
      extracellular proteins. In conclusion polysaccharides have been shown as
      biologically active ingredients of aqueous St. John's Wort extracts with a
      relation between their structural characteristics and function.

PMID- 22848209
TI  - PPARG Epigenetic Deregulation and Its Role in Colorectal Tumorigenesis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) plays critical roles
      in lipid storage, glucose metabolism, energy homeostasis, adipocyte
      differentiation, inflammation, and cancer. Its function in colon carcinogenesis
      has largely been debated; accumulating evidence, however, supports a role as
      tumor suppressor through modulation of crucial pathways in cell differentiation,
      apoptosis, and metastatic dissemination. Epigenetics adds a further layer of
      complexity to gene regulation in several biological processes. In cancer, the
      relationship with epigenetic modifications has provided important insights into
      the underlying molecular mechanisms. These studies have highlighted how
      epigenetic modifications influence PPARG gene expression in colorectal
      tumorigenesis. In this paper, we take a comprehensive look at the current
      understanding of the relationship between PPARgamma and cancer development. The
      role that epigenetic mechanisms play is also addressed disclosing novel
      crosstalks between PPARG signaling and the epigenetic machinery and suggesting
      how this dysregulation may contribute to colon cancer development.

PMID- 22848212
TI  - Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP
      Regulated Differential Expression of NFkappaB and AP-1.
AB  - Background. There are no reported data to explain how Salmonella suppress nitrite
      ion production in macrophages or whether this phenomenon is unique to typhoidal
      or non-typhoidal serovars. The aims of this study were, therefore, to investigate
      these phenomena. Methods. We measured survival of S. typhimurium 14028 and its
      phoP mutant in murine J774 macrophages, cultured with or without interferon
      gamma. We compared expression of inducible nitric oxide synthase (iNOS) mRNA and
      protein, and nitrite ion production and also examined binding of nuclear factor
      kappaB (NFkappaB) and activator protein 1 (AP-1) to macrophage DNA. Results. S.
      typhimurium 14028 inhibited binding of NFkappaB and AP-1 to DNA in murine J774. A
      macrophages via an intact phoP regulon. This correlated with increased survival
      and reduced iNOS expression. Suppression of NFkappaB activity was ameliorated in
      macrophages cultured with IFN-gamma and this correlated with increased expression
      of iNOS mRNA and nitrite ion production, although IFN-gamma had no effect on AP
      1/DNA interaction. We show, that with one exception, suppression of iNOS is
      unique to typhoidal serovars. Conclusion. S. typhimurium inhibit NFkappaB and AP
      1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion
      production and is principally associated with typhoidal serovars.

PMID- 22848213
TI  - pH-Dependent Interaction between C-Peptide and Phospholipid Bicelles.
AB  - C-peptide is the connecting peptide between the A and B chains of insulin in
      proinsulin. In this paper, we investigate the interaction between C-peptide and
      phospholipid bicelles, by circular dichroism and nuclear magnetic resonance
      spectroscopy, and in particular the pH dependence of this interaction. The
      results demonstrate that C-peptide is largely unstructured independent of pH, but
      that a weak structural induction towards a short stretch of beta-sheet is induced
      at low pH, corresponding to the isoelectric point of the peptide. Furthermore, it
      is demonstrated that C-peptide associates with neutral phospholipid bicelles as
      well as acidic phospholipid bicelles at this low pH. C-peptide does not undergo a
      large structural rearrangement as a consequence of lipid interaction, which
      indicates that the folding and binding are uncoupled. In vivo, local variations
      in environment, including pH, may cause C-peptide to associate with lipids, which
      may affect the aggregation state of the peptide.

PMID- 22848214
TI  - Inhibitory effects of arginine on the aggregation of bovine insulin.
AB  - Static and dynamic light scattering were used to investigate the effects of L
      arginine, commonly used to inhibit protein aggregation, on the initial
      aggregation kinetics of solutions of bovine insulin in 20% acetic acid and 0.1 M
      NaCl as a model system for amyloidosis. Measurements were made as a function of
      insulin concentration (0.5-2.0 mM), quench temperature (60-85 degrees C), and
      arginine concentration (10-500 mM). Aggregation kinetics under all conditions had
      a lag phase, whose duration decreased with increasing temperature and with
      increasing insulin concentration but which increased by up to a factor of 8 with
      increasing added arginine. Further, the initial growth rate after the lag phase
      also slowed by up to a factor of about 20 in the presence of increasing
      concentrations of arginine. From the temperature dependence of the lag phase
      duration, we find that the nucleation activation energy doubles from 17 +/- 5 to
      36 +/- 3 kcal/mol in the presence of 500 mM arginine.

PMID- 22848216
TI  - Estimation of Insulin Resistance in Mexican Adults by the [(13)C]Glucose Breath
      Test Corrected for Endogenous Total CO(2) Production.
AB  - Objective. To evaluate the efficacy of the [(13)C]glucose breath test for
      measuring insulin resistance in Mexican adults with different glycemic states.
      Research Design and Methods. Fifty-eight adults underwent a [(13)C]glucose breath
      test with simultaneous measurement of total CO(2) production by indirect
      calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose
      and 25 mg of [(13)C]glucose. HOMA was used as a marker of insulin resistance.
      Results. We found an inverse correlation between HOMA and the breath test
      delta(13)CO(2) (0/00), r = -0.41 (P = 0.001). After adjusting for total CO(2)
      production, correlations between HOMA and fasting glucose were less strong but
      remained significant. An ROC curve was constructed using delta(13)CO(2) (0/00)
      and HOMA values; the cut-off point was 9.990/00 delta(13)CO(2), corresponding to
      a sensitivity of 80.0 (95% CI: 51.9, 95.7) and a specificity of 67.4 (95% CI:
      51.5, 80.9). Conclusions. The [(13)C]glucose breath test is a simple noninvasive
      procedure but was not sufficiently robust for an accurate diagnosis of insulin
      resistance. Our findings suggest that the test might be helpful in identifying
      individuals who are not IR, which in turn may contribute to improved diabetes
      prevention.

PMID- 22848215
TI  - Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism
      Status: A Spanish Population-Based Study (Di@bet.es Study).
AB  - Objective. To evaluate the association between diabetes mellitus and health
      related quality of life (HRQOL) controlled for several sociodemographic and
      anthropometric variables, in a representative sample of the Spanish population.
      Methods. A population-based, cross-sectional, and cluster sampling study, with
      the entire Spanish population as the target population. Five thousand and forty
      seven participants (2162/2885 men/women) answered the HRQOL short form 12
      questionnaire (SF-12). The physical (PCS-12) and the mental component summary
      (MCS-12) scores were assessed. Subjects were divided into four groups according
      to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM),
      and known diabetes (KDM). Logistic regression analyses were conducted. Results.
      Mean PCS-12/MCS-12 values were 50.9 +/- 8.5/ 47.6 +/- 10.2, respectively. Men had
      higher scores than women in both PCS-12 (51.8 +/- 7.2 versus 50.3 +/- 9.2; P <
      0.001) and MCS-12 (50.2 +/- 8.5 versus 45.5 +/- 10.8; P < 0.001). Increasing age
      and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and
      MCS-12 scores were associated with a higher level of glucose metabolism
      abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS
      12 score was associated with altered glucose levels in men (P < 0.001 for trend).
      The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for
      a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men
      with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001),
      respectively. Conclusion. Current study indicates that increasing levels of
      altered carbohydrate metabolism are accompanied by a trend towards decreasing
      quality of life, mainly in women, in a representative sample of Spanish
      population.

PMID- 22848217
TI  - Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast
      PET.
AB  - Positron emission tomography (PET), with or without integrated computed
      tomography (CT), using 18F-fluorodeoxyglucose (FDG) is based on the principle of
      elevated glucose metabolism in malignant tumors, and its use in breast cancer
      patients is frequently being investigated. It has been shown useful for
      classification, staging, and response monitoring, both in primary and recurrent
      disease. However, because of the partial volume effect and limited resolution of
      most whole-body PET scanners, sensitivity for the visualization of small tumors
      is generally low. To improve the detection and quantification of primary breast
      tumors with FDG PET, several dedicated breast PET devices have been developed. In
      this nonsystematic review, we shortly summarize the value of whole-body PET/CT in
      breast cancer and provide an overview of currently available dedicated breast
      PETs.

PMID- 22848218
TI  - Can a Gleason 6 or Less Microfocus of Prostate Cancer in One Biopsy and Prostate
      Specific Antigen Level <10 ng/mL Be Defined as the Archetype of Low-Risk Prostate
      Disease?
AB  - Prostate cancer (PC) remains a cause of death worldwide. Here we investigate
      whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less,
      <=5% occupancy) and the PSA <10 ng/mL can define the archetype of low-risk
      prostate disease. 4500 consecutive patients were enrolled. Among them, 134
      patients with a single micro-focus of PC were followed up, and the parameters
      influencing the biochemical relapse (BR) were analysed. Out of 134 patients, 94
      had clinically significant disease, specifically in 74.26% of the patients with
      PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were
      found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the
      patients. Cox regression evidenced a correlation between the BR and Gleason grade
      at the retropubic radical prostatectomy (RRP), capsular invasion, and the
      presence of positive surgical margins. Multivariate regression analysis showed a
      statistically significant correlation between the presence of surgical margins at
      the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA
      serum level <10 ng/mL, clinically significant disease was found in 74.26%
      patients and only positive surgical margins are useful for predicting the BR.

PMID- 22848219
TI  - MicroRNAs in Human Malignant Gliomas.
AB  - MicroRNA (miRNA) is a new class of small noncoding RNA molecules that regulate a
      wide spectrum of gene expression in a posttranscriptional manner. MiRNAs play
      crucial roles in tumorigenesis, angiogenesis, invasion, and apoptosis for various
      types of tumor. Recent studies have identified dysregulation of specific miRNAs
      in malignant gliomas. Global expression profiling of miRNAs has revealed several
      miRNAs clinically implicated in human glioblastomas. Some miRNAs are clearly
      associated with clinical outcome and chemo- and radio-therapy resistance in these
      tumors. Furthermore, miRNAs also regulate specific signaling pathways, including
      the critical core pathways in glioblastoma. As a result, miRNAs have the
      potential to affect the responses to molecular-targeted therapies. More recent
      studies have revealed that miRNAs might be associated with cancer stem cell
      properties, affecting tumor maintenance and progression. Recent investigation
      have revealed that miRNAs are not only biological markers with diagnostic
      implications, but also one of the most promising treatment targets in human
      glioblastoma. Herein, we summarized the novel insights of miRNAs into human
      malignant gliomas.

PMID- 22848220
TI  - Stem cells as a tool for breast imaging.
AB  - Stem cells are a scientific field of interest due to their therapeutic potential.
      There are different groups, depending on the differentiation state. We can find
      lonely stem cells, but generally they distribute in niches. Stem cells don't
      survive forever. They are affected for senescence. Cancer stem cells are best
      defined functionally, as a subpopulation of tumor cells that can enrich for
      tumorigenic property and can regenerate heterogeneity of the original tumor.
      Circulating tumor cells are cells that have detached from a primary tumor and
      circulate in the bloodstream. They may constitute seeds for subsequent growth of
      additional tumors (metastasis) in different tissues. Advances in molecular
      imaging have allowed a deeper understanding of the in vivo behavior of stem cells
      and have proven to be indispensable in preclinical and clinical studies. One of
      the first imaging modalities for monitoring pluripotent stem cells in vivo,
      magnetic resonance imaging (MRI) offers high spatial and temporal resolution to
      obtain detailed morphological and functional information. Advantages of
      radioscintigraphic techniques include their picomolar sensitivity, good tissue
      penetration, and translation to clinical applications. Radionuclide imaging is
      the sole direct labeling technique used thus far in human studies, involving both
      autologous bone marrow derived and peripheral stem cells.

PMID- 22848221
TI  - Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in
      Leukemic NOD/SCID Mouse In Vivo.
AB  - We recently reported that chronic myelogenous leukemia (CML) cells converted into
      myofibroblasts to create a microenvironment for proliferation of CML cells in
      vitro. To analyze a biological contribution of CML-derived myofibroblasts in
      vivo, we observed the characters of leukemic nonobese diabetes/severe combined
      immunodeficiency (NOD/SCID) mouse. Bone marrow nonadherent mononuclear cells as
      well as human CD45-positive cells obtained from CML patients were injected to the
      irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated
      in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML
      derived myofibroblasts composed with the bone marrow-stroma, which produced
      significant amounts of human vascular endothelial growth factor A. When the
      parental CML cells were cultured with myofibroblasts separated from CML cell
      engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly.
      These observations indicate that CML cells make an adequate microenvironment for
      their own proliferation in vivo.

PMID- 22848222
TI  - Do Breast Cancer Patients Tested in the Oncology Care Setting Share BRCA Mutation
      Results with Family Members and Health Care Providers?
AB  - BRCA genetic test results provide important information to manage cancer risk for
      patients and their families. Little is known on the communication of genetic test
      results by mutation status with family members and physicians in the oncology
      care setting. As part of a longitudinal study evaluating the impact of genetic
      counseling and testing among recently diagnosed breast cancer patients, we
      collected patients' self-reported patterns of disclosure. Descriptive statistics
      characterized the sample and determined the prevalence of disclosure of BRCA test
      results to family members and physicians. Of 100 patients who completed the
      baseline and the 6-month followup survey, 77 reported pursuing testing. The
      majority shared test results with female first-degree relatives; fewer did with
      males. Participants were more likely to share results with oncologists compared
      to surgeons, primary care physicians, or other specialty physicians. These
      findings suggest that while breast cancer patients may communicate results to at
      risk female family members and their medical oncologist, they may need education
      and support to facilitate communication to other first-degree relatives and
      providers.

PMID- 22848223
TI  - Schneider membrane elevation in presence of sinus septa: anatomic features and
      surgical management.
AB  - Maxillary sinus floor elevation via a lateral approach is a predictable technique
      to increase bone volume of the edentulous posterior maxilla and consequently for
      dental implants placement. The sinus floor is elevated and it can be augmented
      with either autologous or xenogeneic bone grafts following an opening bone window
      created on the facial buccal wall. Maxillary septa are walls of cortical bone
      within the maxillary sinus. The septa shape has been described as an inverted
      gothic arch arising from the inferior or lateral walls of the sinus and may even
      divide the sinus into two or more cavities. Some authors have reported a higher
      prevalence of septa in atrophic edentulous areas than in nonatrophic ones.
      Radiographic identification of these structures is important in order to perform
      the right design of the lateral window during sinus lift. Aim of this
      investigation is to highlight the correct steps for doing sinus lift surgery in
      presence of those anatomic variations. Clinicians should always perform clinical
      and radiographic diagnosis in order to avoid complications related to the sinus
      lift surgery.

PMID- 22848226
TI  - Disseminated exfoliative dermatitis associated with all-transretinoic Acid in the
      treatment of acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a biologically and clinically separate type
      of acute myeloid leukemia characterized by a translocation involving the retinoic
      acid receptor-alpha (RARa) locus on chromosome 17, the great majority of which is
      t(15; 17)(q24.1; q21.1) (Collins (1998), Melnick and Licht (1999), and Grimwade
      (1999)). Retinoic acid is a critical ligand in the differentiation pathway of
      multiple tissues, mediated through binding to an RAR. All-trans retinoic acid
      (ATRA) is a subgroup of the retinoid family, which induces complete remission
      (CR) in APL by causing differentiation and apoptosis in immature malignant
      promyelocytes rather than inducing cell death by cytotoxicity (Warrell et al.
      (1993), Liu et al. (2000), and Cassinat et al. (2001)). ATRA-associated toxicity
      consisting of headache, fever, weakness, fatigue, dry skin, dermatitis,
      gastrointestinal disorders, and hypertriglyceridemia has been shown to be mild
      (Kurzrock et al. (1993)). Herein, we describe a patient with APL that developed
      an erythematous reaction of the whole body followed by desquamation and
      exfoliation during ATRA therapy.

PMID- 22848225
TI  - Is lifelong knee joint force from work, home, and sport related to knee
      osteoarthritis?
AB  - Purpose. To investigate the association of cumulative lifetime knee joint force
      on the risk of self-reported medically-diagnosed knee osteoarthritis (OA).
      Methods. Exposure data on lifetime physical activity type (occupational,
      household, sport/recreation) and dose (frequency, intensity, duration) were
      collected from 4,269 Canadian men and women as part of the Physical Activity and
      Joint Heath cohort study. Subjects were ranked in terms of the "cumulative peak
      force index", a measure of lifetime mechanical knee force. Multivariable logistic
      regression was conducted to obtain adjusted effects for mean lifetime knee force
      on the risk of knee OA. Results. High levels of total lifetime, occupational and
      household-related force were associated with an increased in risk of OA, with
      odds ratio's ranging from approximately 1.3 to 2. Joint injury, high BMI and
      older age were related to risk of knee OA, consistent with previous studies.
      Conclusions. A newly developed measure of lifetime mechanical knee force from
      physical activity was employed to estimate the risk of self-reported, medically
      diagnosed knee OA. While there are limitations, this paper suggests that high
      levels of total lifetime force (all domains combined), and occupational force in
      men and household force in women were risk factors for knee OA.

PMID- 22848224
TI  - Microbial translocation in chronic liver diseases.
AB  - The intestinal microflora is not only involved in the digestion of nutrients, but
      also in local immunity, forming a barrier against pathogenic microorganisms. The
      derangement of the gut microflora may lead to microbial translocation, defined as
      the passage of viable microorganisms or bacterial products (i.e., LPS,
      lipopeptides) from the intestinal lumen to the mesenteric lymph nodes and other
      extraintestinal sites. The most recent evidence suggests that microbial
      translocation (MT) may occur not only in cirrhosis, but also in the early stage
      of several liver diseases, including alcoholic hepatopathy and nonalcoholic fatty
      liver disease. Different mechanisms, such as small intestinal bacterial
      overgrowth, increased permeability of intestinal mucosa, and impaired immunity,
      may favor MT. Furthermore, MT has been implicated in the pathogenesis of the
      complications of cirrhosis, which are a significant cause of morbidity and
      mortality in cirrhotic subjects. Therapeutic strategies aiming at modulating the
      gut microflora and reducing MT have focused on antibiotic-based options, such as
      selective intestinal decontamination, and nonantibiotic-based options, such as
      prokinetics and probiotics. In particular, probiotics may represent an attractive
      strategy, even though the promising results of experimental models and limited
      clinical studies need to be confirmed in larger randomized trials.

PMID- 22848227
TI  - Ion channel activities in neural stem cells of the neuroepithelium.
AB  - During the embryonic development of the central nervous system, neuroepithelial
      cells act as neural stem cells. They undergo interkinetic nuclear movements along
      their apico-basal axis during the cell cycle. The neuroepithelial cell shows
      robust increases in the nucleoplasmic [Ca(2+)] in response to G protein-coupled
      receptor activation in S-phase, during which the nucleus is located in the basal
      region of the neuroepithelial cell. This response is caused by Ca(2+) release
      from intracellular Ca(2+) stores, which are comprised of the endoplasmic
      reticulum and the nuclear envelope. The Ca(2+) release leads to the activation of
      Ca(2+) entry from the extracellular space, which is called capacitative, or store
      operated Ca(2+) entry. These movements of Ca(2+) are essential for DNA synthesis
      during S-phase. Spontaneous Ca(2+) oscillations also occur synchronously across
      the cells. This synchronization is mediated by voltage fluctuations in the
      membrane potential of the nuclear envelope due to Ca(2+) release and the counter
      movement of K(+) ions; the voltage fluctuation induces alternating current (AC),
      which is transmitted via capacitative electrical coupling to the neighboring
      cells. The membrane potential across the plasma membrane is stabilized through
      gap junction coupling by lowering the input resistance. Thus, stored Ca(2+) ions
      are a key player in the maintenance of the cellular activity of neuroepithelial
      cells.

PMID- 22848228
TI  - Development of a vascularized skin construct using adipose-derived stem cells
      from debrided burned skin.
AB  - Large body surface area burns pose significant therapeutic challenges.
      Clinically, the extent and depth of burn injury may mandate the use of allograft
      for temporary wound coverage while autografts are serially harvested from the
      same donor areas. The paucity of donor sites in patients with burns involving
      large surface areas highlights the need for better skin substitutes that can
      achieve early and complete coverage and retain normal skin durability with
      minimal donor requirements. We have isolated autologous stem cells from the
      adipose layer of surgically debrided burned skin (dsASCs), using a point-of-care
      stem cell isolation device. These cells, in a collagen-polyethylene glycol fibrin
      based bilayer hydrogel, differentiate into an epithelial layer, a vascularized
      dermal layer, and a hypodermal layer. All-trans-retinoic acid and fenofibrate
      were used to differentiate dsASCs into epithelial-like cells. Immunocytochemical
      analysis showed a matrix- and time-dependent change in the expression of stromal,
      vascular, and epithelial cell markers. These results indicate that stem cells
      isolated from debrided skin can be used as a single autologous cell source to
      develop a vascularized skin construct without culture expansion or addition of
      exogenous growth factors. This technique may provide an alternative approach for
      cutaneous coverage after extensive burn injuries.

PMID- 22848229
TI  - Comparison of the Triage Micro Parasite Panel and Microscopy for the Detection of
      Entamoeba histolytica/Entamoeba dispar, Giardia lamblia, and Cryptosporidium
      parvum in Stool Samples Collected in Kenya.
AB  - Entamoeba histolytica,  Giardia lamblia, and Cryptosporidium parvum are three of
      the most important parasitic causes of acute diarrhea worldwide. Laboratory
      diagnosis of these parasites is usually done by ova and parasite examination (O&P
      examination) via microscopy. The sensitivity and specificity of O&P examination
      varies among laboratories and can be labor intensive and time consuming. The
      Triage Micro Parasite Panel (BioSite, San Diego, California) is an enzyme
      immunoassay kit that can detect E. histolytica/E. dispar, G. lamblia, and C.
      parvum simultaneously using fresh or frozen stool. The present study evaluated
      the Triage Micro Parasite Panel in detecting E. histolytica/E. dispar, G.
      lamblia, and C. parvum compared to O&P examination in 266 stool samples collected
      at medical facilities in Kenya. The sensitivity and specificity results for the
      Triage Micro Parasite Panel were: for E. histolytica/E. dispar: 100%, 100%, G.
      lamblia: 100%, 100% and C. parvum: 73%, 100%. There was no evidence of cross
      reactivity using the kit with other parasites identified in the stool specimens.
      These results indicate that the Triage Micro Parasite Panel is a highly sensitive
      kit that can be used for screening purposes in large scale studies or outbreak
      investigations or as a possible alternative to O&P examination.

PMID- 22848230
TI  - Life situation and identity among single older home-living people: a
      phenomenological-hermeneutic study.
AB  - Being able to continue living in their own home as long as possible is the
      general preference for many older people, and this is also in line with the
      public policy in the Nordic countries. The aim of this study was to elucidate the
      meaning of self-care and health for perception of life situation and identity
      among single-living older individuals in rural areas in southern Norway. Eleven
      older persons with a mean age of 78 years were interviewed and encouraged to
      narrate their self-care and health experiences. The interviews were audio taped,
      transcribed verbatim and analysed using a phenomenological-hermeneutic method
      inspired by the philosophy of Ricoeur. The findings are presented as a naive
      reading, an inductive structural analysis characterized by two main themes; i.e.,
      "being able to do" and "being able to be", and a comprehensive interpretation.
      The life situation of the interviewed single-living older individuals in rural
      areas in southern Norway was interpreted as inevitable, appropriate and
      meaningful. Their identity was constituted by their freedom and self-chosen
      actions in their personal contexts. The overall impression was that independence
      and the ability to control and govern their own life in accordance with needs and
      preferences were ultimate goals for the study participants.

PMID- 22848231
TI  - The relationship between tuberculosis and influenza death during the influenza
      (H1N1) pandemic from 1918-19.
AB  - The epidemiological mechanisms behind the W-shaped age-specific influenza
      mortality during the Spanish influenza (H1N1) pandemic 1918-19 have yet to be
      fully clarified. The present study aimed to develop a formal hypothesis:
      tuberculosis (TB) was associated with the W-shaped influenza mortality from 1918
      19. Three pieces of epidemiological information were assessed: (i) the epidemic
      records containing the age-specific numbers of cases and deaths of influenza from
      1918-19, (ii) an outbreak record of influenza in a Swiss TB sanatorium during the
      pandemic, and (iii) the age-dependent TB mortality over time in the early 20th
      century. Analyzing the data (i), we found that the W-shaped pattern was not only
      seen in mortality but also in the age-specific case fatality ratio, suggesting
      the presence of underlying age-specific risk factor(s) of influenza death among
      young adults. From the data (ii), TB was shown to be associated with influenza
      death (P = 0.09), and there was no influenza death among non-TB controls. The
      data (iii) were analyzed by employing the age-period-cohort model, revealing
      harvesting effect in the period function of TB mortality shortly after the 1918
      19 pandemic. These findings suggest that it is worthwhile to further explore the
      role of TB in characterizing the age-specific risk of influenza death.

PMID- 22848232
TI  - The emerging role of CXCL10 in cancer (Review).
AB  - The chemokine interferon-gamma inducible protein 10 kDa (CXCL10) is a member of
      the CXC chemokine family which binds to the CXCR3 receptor to exert its
      biological effects. CXCL10 is involved in chemotaxis, induction of apoptosis,
      regulation of cell growth and mediation of angiostatic effects. CXCL10 is
      associated with a variety of human diseases including infectious diseases,
      chronic inflammation, immune dysfuntion, tumor development, metastasis and
      dissemination. More importantly, CXCL10 has been identified as a major biological
      marker mediating disease severity and may be utilized as a prognostic indicator
      for various diseases. In this review, we focus on current research elucidating
      the emerging role of CXCL10 in the pathogenesis of cancer. Understanding the role
      of CXCL10 in disease initiation and progression may provide the basis for
      developing CXCL10 as a potential biomarker and therapeutic target for related
      human malignancies.

PMID- 22848233
TI  - The role of components of the chromatin modification machinery in carcinogenesis
      of clear cell carcinoma of the ovary (Review).
AB  - Recent data have provided information regarding the profiles of clear cell
      carcinoma of the ovary (CCC) with adenine-thymine rich interactive domain 1A
      (ARID1A) mutations. The purpose of this review was to summarize current knowledge
      regarding the molecular mechanisms involved in CCC tumorigenesis and to describe
      the central role played by the aberrant chromatin remodeling. The present article
      reviews the English-language literature for biochemical studies on the ARID1A
      mutation and chromatin remodeling in CCC. ARID1A is responsible for directing the
      SWI/SNF complex to target promoters and regulates the transcription of certain
      genes by altering the chromatin structure around those genes. The mutation
      spectrum of ARID1A was enriched for C to T transitions. CCC and clear cell renal
      cell carcinoma (ccRCC) resemble each other pathogenetically. Dysfunction of the
      ARID1A protein, which occurs with VHL mutations in ccRCC, is responsible for loss
      of the assembly of the ARID1A-mediated histone H2B complex. Therefore, ARID1A
      acts as a chromatin remodeling modifier, which stimulates cell signaling that can
      lead to cell cycle arrest and cell death in the event of DNA damage. The
      dysfunction of ARID1A may result in susceptibility to CCC carcinogenesis through
      a defect in the repair or replication of damaged DNA.

PMID- 22848235
TI  - Involvement of WRN helicase in immortalization and tumorigenesis by the telomeric
      crisis pathway (Review).
AB  - The repeated replication of cells shortens telomeres, culminating in their
      instability, after which most cells cease to replicate and die. However, a small
      fraction of the cells become immortalized by maintaining telomeres with activated
      telomerase activity. It has been proposed that WRN helicase encoded by the WRN
      gene, the causative gene of Werner syndrome (WS), is required for immortalization
      by the telomeric crisis pathway (TCP) in a system that uses lymphoblastoid cell
      lines transformed by the Epstein-Barr virus. Taken together, these
      characteristics indicate that WRN helicase is also required for the
      immortalization of epithelial cells by TCP and consequent carcinogenesis,
      suggesting that the tumorigenesis of epithelial cells by TCP is suppressed in WS
      lacking the WRN helicase function. Notably, in WS the pathway of alternative
      lengthening of telomeres without activation of telomerase activity has been
      suggested to be involved in immortalization and tumorigenesis. This factor is
      consistent with the abundance of non-epithelial cancers in WS in that the ratio
      of epithelial to non-epithelial cancers is approximately 1:1 in WS patients
      compared to 10:1 in the general population. A hypothetical scheme showing the
      role of WRN helicase in immortalization by means of the supposed 'breakage-fusion
      bridge cycle' of chromosomes at telomeric crisis is described.

PMID- 22848236
TI  - MicroRNA profiling of gastric cancer patients from formalin-fixed paraffin
      embedded samples.
AB  - MicroRNA (miRNA) is a small non-coding RNA that targets specific mRNA. Recent
      progress in the extraction of RNA from formalin-fixed paraffin-embedded (FFPE)
      tissues has facilitated miRNA profiling using samples stored in laboratories
      worldwide. In the present study, miRNA profiling of gastric cancer patients is
      determined using FFPE samples. First, criteria were established for determining
      evaluable RNA from the FFPE samples. miRNA profiling was then undertaken using
      miRNA oligo chips with 885 featured genes. The FFPE samples were obtained from 47
      gastric cancer patients who underwent operations between 1997 and 2007. Results
      showed that out of 47 paired samples, 37 pairs (78.8%) were evaluable by our
      criteria. A total of 30 miRNAs were significantly up-regulated and 11 miRNAs were
      down-regulated in gastric cancer compared with those in normal gastric tissue.
      Among these, 14 miRNAs, including miR-21, were identified as prognostic factors
      of gastric cancer patients. Furthermore, miR-34a was selected as an independent
      prognostic factor. In conclusion, we identified miRNAs that are associated with
      the prognosis of gastric cancer patients. miRNA profiling using FFPE samples is a
      useful and promising method of evaluation for samples stored in laboratories
      worldwide, and can generate extremely valuable clinical data.

PMID- 22848237
TI  - A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission
      tomography/computed tomography (PET/CT) one year after the detection of
      metastatic brain tumor.
AB  - Cancer of unknown primary origin (CUP) is an aggressive disease with a poor
      prognosis. Metastatic brain tumors occur in approximately 15% of all cancer
      patients. F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography
      (PET) combined with computed tomography (PET/CT) contributes to the evaluation of
      cancer staging, although the benefits of PET/CT for detection of CUP origins has
      yet to be determined. In this study, we present a 37-year-old man with a brain
      tumor detected by magnetic resonance imaging. Surgical biopsy indicated a
      metastatic undifferentiated carcinoma, while clinical examination and a CT scan
      did not detect any abnormalities, with the exception of brain metastases. PET/CT
      did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake
      in a small nodular lesion in the right lung 1 year following the detection of
      brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the
      body. Right upper lobectomy and dissection of mediastinal lymph nodes were
      performed. The pathological diagnosis was poorly differentiated adenocarcinoma,
      which was similar to the brain metastatic lesion, and there was no lymph node
      metastasis. This case revealed an extremely rare lung cancer with primary lesions
      demonstrated by PET/CT 1 year after the detection of brain metastasis. This case
      reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively
      impacting on the identification of small primary tumor foci.

PMID- 22848234
TI  - Protease-activated receptors in cancer: A systematic review.
AB  - The traditional view of the role of proteases in tumor growth, progression and
      metastasis has significantly changed. Apart from their contribution to cancer
      progression, it is evident that a subclass of proteases, such as thrombin, serves
      as signal molecules controlling cell functions through the protease-activated
      receptors (PARs). Among the four types of PAR (PAR1-4; cloned and named in order
      of their discovery), PAR1, PAR3 and PAR4 are activated by thrombin, unlike PAR2,
      which is activated by trypsin-like serine proteases. Thrombin has been proven to
      be a significant factor in both the behavior of cancer in its involvement in
      hemostasis and blood coagulation. Thrombin is a key supporter of various cellular
      effects relevant to tumor growth and metastasis, as well as a potent activator of
      angiogenesis, which is essential for the growth and development of all solid
      tumor types. This review presents an overview of the role of PAR-mediated
      thrombin in angiogenesis and cancer, focusing on the ability of PAR1- and PAR4
      mediated thrombin to affect tumorigenesis and angiogenesis.

PMID- 22848238
TI  - Basal cell carcinoma arising within a seborrheic keratosis with respect to
      immunohistochemical characteristics.
AB  - Malignant tumor occurring within seborrheic keratosis (SK), which is one of the
      most common benign cutaneous tumors, is extremely rare. We report a case of basal
      cell carcinoma (BCC) arising within SK. Additionally, this is the first study to
      describe the immunohistochemical characteristics of this type of carcinoma. An 89
      year-old Japanese woman presented with a persistent scaly plaque in the right
      auricle of her ear. Histopathological study revealed a superficial type of BCC
      arising within SK. Immunohistochemical studies showed that cytokeratin 17 (CK17),
      CK19, SOX9 and p53 protein were expressed in BCC, but not in SK. BCC is
      considered to originate from the follicular germinative cells, and the outer root
      sheath may be the possible origin. SK is also thought to be a benign skin
      appendage neoplasm showing follicular differentiation, especially follicular
      infundibula. Therefore, previous reports speculated that there was a pathogenic
      relationship between SK and BCC, with respect to a common follicular origin.
      However, the immunohistochemical characteristics of this study suggest that BCC
      does not arise directly from SK, but instead, that SK is the nidus of the
      carcinoma, resulting in the abutment of SK with BCC. Furthermore, the results of
      the present case suggest that immunohistochemical surveillance of the expression
      of CK17, CK19 and SOX9 and p53 protein is useful in differentiating minute BCC
      from the non-neoplastic hair buds.

PMID- 22848239
TI  - Establishment of primary mouse lung adenocarcinoma cell culture.
AB  - Lung cancer is the most common malignant disease worldwide and is the leading
      cause of death from cancer. Primary cultures derived from lung cancer are
      essential for understanding abnormal growth function in lung epithelia. In this
      study, 2 out of 5 primary lung adenocarcinoma cultures derived from DNA repair
      deficient mice were established and characterised using electron microscopy and
      immunostaining. Results of the tumourigenicity tests confirmed that these primary
      cells are tumourigenic. In conclusion, an effective primary culture method
      provides a tool for clinical antitumour drug testing.

PMID- 22848240
TI  - Retroperitoneal primary mucinous adenocarcinoma: A case report.
AB  - Retroperitoneal primary mucinous adenocarcinoma (RPMA) is extremely rare and the
      histogenesis of this tumor remains unclear. There is no consensus on the
      appropriate treatment for RPMA. Surgical resection is standard for the treatment
      of RPMA, whereas the benefits of chemotherapy with regard to this tumor remain to
      be established. This case report concerns a 21-year-old female individual with
      RPMA. The patient initially presented with chronic lower back pain and weight
      loss. Additionally, carcinoembryonic antigen (CEA) levels were found to be
      elevated. A computed tomography scan revealed a mass in the abdominal cavity.
      Consequently, laparotomy was performed, which revealed a well-defined tumor in
      the right retroperitoneum. Chemotherapy as a monotherapy was not considered as a
      viable treatment option. Therefore, the patient was initially administered a
      combined treatement of oxaliplatin and 5-fluorouracil. This treatment was then
      changed to paclitaxel and 5-fluorouracil. Findings showed a decrease in the CEA
      serum levels, indicating that this combination treatment may be efficacious in
      the treatment of RPMA since local recurrence following surgical resection was
      well controlled with chemotherapy.

PMID- 22848241
TI  - Screening the pathogenic genes and pathways related to DMBA (7,12
      dimethylbenz[a]anthracene)-induced transformation of hamster oral mucosa from
      precancerous lesions to squamous cell carcinoma.
AB  - This study aimed to screen the pathogenic genes and pathways that relate to the
      transformation of hamster buccal mucosa from precancerous lesions to squamous
      cell carcinoma by whole genome microarray and bioinformatics analysis. A DMBA
      (7,12-dimethylbenz[a]anthracene)-induced hamster model of a precancerous lesion
      and squamous cell carcinoma was established. The differentially expressed genes
      were detected using an Agilent whole rat genome microarray, which contains 41,000
      genes/ESTs. Gene ontology (GO) functional classification and pathway analyses
      were performed, and a subset of differentially expressed genes were validated
      using RT-PCR. The results showed that during the transformation of hamster buccal
      mucosa from the precancerous lesion to squamous cell carcinoma, a total of 1,981
      genes were differentially expressed, of which 1,037 were up-regulated and 944
      were down-regulated. GO analysis revealed that the differentially expressed genes
      are mainly involved in 14 functional groups including those of metabolism and
      cell structure. Additionally, 9 significantly altered pathways were identified.
      Among the 1,861 known differentially expressed genes, 14 genes including Casp3,
      CCL5 and CXCL12 were enriched in the 9 altered pathways. The up-regulation of
      SPARC and down-regulation of Casp3 were confirmed by RT-PCR. In conclusion, a
      total of 1,981 differentially expressed genes and 9 significantly altered
      pathways were identified in the transformation of hamster buccal mucosa from
      precancerous lesions to squamous cell carcinoma. A total of 14 pathway-enriched
      genes including Casp3, CCL5 and CXCL12 may play critical roles in the alteration
      of cellular pathways leading to the transformation of buccal mucosa from
      precancerous lesions to squamous cell carcinoma. Future studies focusing on these
      genes and pathways are required in order to gain a better understanding and
      provide effective prevention and treatment of oral squamous cell carcinoma.

PMID- 22848242
TI  - Rapamycin synergizes with low-dose oxaliplatin in the HCT116 colon cancer cell
      line by inducing enhanced apoptosis.
AB  - The present study aimed to examine the combined effects of oxaliplatin (L-OHP)
      and rapamycin (RAPA) in the HCT116 colon cancer cell line. The growth inhibitory
      effect was evaluated by MTT assay as a monotherapy or combination therapy. IC(50)
      values were determined using CalcuSyn 2.0 software. To determine the interaction
      of the drugs, the combination index (CI) was calculated using the Chou-Talalay
      method. Apoptosis was investigated using flow cytometry and Western blotting.
      Acridine orange staining was employed to observe morphological changes. The
      results showed the IC(50) values of L-OHP and RAPA to be 8.35+/-0.78 MUM (r=0.99)
      and 223.44+/-38.10 nM (r=0.94), respectively. CI was <=1 when L-OHP was used at
      doses ranging from 1 to 5 MUM plus RAPA at a dose of 10 nM, suggesting
      synergistic or additive effects. CI was >=1 when 100 nM RAPA was used in
      combination with low-dose L-OHP, showing additive to antagonistic effects. The
      combination of L-OHP (1 MUM) and RAPA (10 nM) induced 19.76% Annexin V-positive
      cells, which was found to be higher than L-OHP (11.45%, p<0.01) or RAPA (6.89%,
      p<0.01) alone. The cleaved PARP protein expression levels were highest after 48 h
      of combination treatment. Acridine orange staining showed typical bright red
      Acidic vesicular organelles in the RAPA group, whereas the green condensed
      chromatin in the apoptotic bodies was found in both the L-OHP and combination
      groups. In conclusion, at a cytostatic concentration, RAPA was found to
      potentiate the anti-tumor effects of low-dose L-OHP in the HCT116 colon cancer
      cell by inducing enhanced apoptosis.

PMID- 22848243
TI  - Extranodal follicular dendritic cell sarcoma in mesentery: A case report.
AB  - Extranodal follicular dendritic cell (FDC) sarcomas are not a common phenomenon.
      Due to the scarcity of the identified cases reported in the literature, FDC is
      probably under-recognized and commonly misdiagnosed. The diagnosis of FDC
      sarcomas is based on node-based spindle cell lesions, and the expression of CD21,
      CD35 and clusterin. The most commonly involved extranodal sites include the oral
      cavity, tonsil, gastrointestinal tract and liver. With the aid of
      immunohistochemical analysis and the two most reliable FDC markers, CD21 and
      CD35, the diagnostic accuracy has improved. When FDC sarcoma is suspected
      histologically, immunohistochemical stains for FDC differentiation should be
      performed to avoid potential misdiagnosis. This case report concerns the
      evaluation of a 43-year-old male Chinese patient with a large extranodal FDC
      sarcoma (20*18*9 cm) in the mesentery with elevated serum CA125 (76.9 U/ml). The
      diagnosis and treatment of this disease are also discussed.

PMID- 22848244
TI  - A functional polymorphism of TGFBR2 is associated with risk of breast cancer with
      ER(+), PR(+), ER(+)PR(+) and HER2(-) expression in women.
AB  - Little is known about the correlation between TGFBR2 G-875A and breast cancer
      risk. Moreover, the associations of the expression of estrogen receptor (ER),
      progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) in
      breast cancer tissues with the TGFB1 C-509T, T+29C and TGFBR2 G-875A
      polymorphisms remain to be determined. In this study, we genotyped for TGFB1 C
      509T, T+29C and TGFBR2 G-875A in fresh surgically resected tissues (n=82) and
      archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer,
      as well as peripheral blood samples from 178 cancer-free female individuals.
      Evaluation of ER, PR and HER2 expression was performed using immunohistochemical
      staining. Logistic regression analysis was carried out to determine the risk of
      breast cancer by calculating the odds ratios (ORs) and their 95% confidence
      intervals (CIs). As a result, no difference was observed in the TGFB1 C-509T,
      T+29C genotype and allele frequencies between patients and controls. However, the
      frequency of the TGFBR2 -875A allele was marginally higher in cancer-free female
      individuals than that of women with breast cancer (24.2 vs. 17.9%, P=0.05).
      Notably, when stratification was performed by ER, PR and HER2 expression, the
      TGFBR2 -875A allele was found to correlate significantly to a decreased risk of
      breast cancer with ER(+) (OR=0.57, 95% CI 0.35-0.92), PR(+) (OR=0.54, 95% CI 0.34
      0.88), ER(+)PR(+) (OR=0.55, 95% CI 0.33-0.92) and HER2(-) (OR=0.55, 95% CI 0.34
      0.88) under a dominant genetic model. In conclusion, this is the first study to
      suggest that the TGFBR2 -875A allele modifies predisposition to breast cancer
      with an expression of ER(+), PR(+), ER(+)PR(+) and HER2(-).

PMID- 22848245
TI  - CD38 expression as response of hematopoietic system to cancer.
AB  - Erythrocyte and lymphocyte NAD(+) glycohydrolase levels were previously found to
      be elevated in cancer patients. These results were confirmed in an animal model.
      The administration of live Ehrlich ascites tumor cells to BALB/c mice led to
      increases in erythrocyte and lymphocyte NAD(+) glycohydrolase, along with tumor
      development. Serum samples, ascites fluid from mice with developed tumors, serum
      samples from cancer patients and Ehrlich cell supernatants had a similar
      stimulatory effect when administered to mice or when incubated with peripheric
      lymphocytes in culture. These increases were accompanied by the appearance of an
      anti-CD38 reactive band of 45 kDa in SDS-PAGE/Western blot analyses of
      erythrocyte ghost and lymphocyte membrane proteins. The results, supported by
      flow cytometry data, support previous clinical findings that an enhancement in
      CD38 expression occurs in the hematopoietic system during proliferative
      processes. Moreover, they suggest that CD38 expression is triggered at least in
      part by a certain cytokine(s) secreted by cancer cells. Finally, the results
      emphasize the prospective use of CD38 expression as a marker of tumor development
      and progression.

PMID- 22848246
TI  - Tumor suppressor and T-regulatory functions of Foxp3 are mediated through
      separate signaling pathways.
AB  - Foxp3 is a nuclear transcription factor that is both a tumor suppressor factor
      and regulator of T-regulatory cell (Treg) function, and is a potential
      therapeutic target in both autoimmunity and cancer. In order to distinguish
      molecular pathways responsible for these separate Foxp3 functions, deletion
      mutants of Foxp3 proteins were transduced and analyzed for cytotoxic activity in
      human cancer cell lines Skov3, MDA-MB-231, MCF-7 and Jurkat. Human Foxp3 cDNA
      mutants were amplified and ligated to produce plasmids for direct cell
      transfection. Constructs were produced and confirmed by DNA sequencing.
      Lipofectamine 2000 was used for plasmid transfection. Foxp3 cells were then
      examined. The results of our experiments reveal retention of tumor suppressor
      function in the absence of NFAT binding and transcriptional activation required
      for Treg function. Our results have significant implications for the design of
      autoimmune and cancer therapies that target Foxp3 and Treg cells.

PMID- 22848247
TI  - High-dose 3-dimensional conformal radiotherapy with concomitant vinorelbine plus
      carboplatin in patients with non-small cell lung cancer: A feasibility study.
AB  - The aim of this study was to evaluate the feasibility of high-dose 3-dimensional
      conformal radiotherapy (3DCRT) (70 Gy) with concomitant vinorelbine (NVB) plus
      carboplatin (CBP) chemotherapy in patients with non-small cell lung cancer
      (NSCLC). Patients with advanced NSCLC were treated with 3-dimensional conformal
      radiotherapy in conventional fractionation: 2 Gy/fraction, 1 fraction/day, 5
      fractions/week; total dose 70 Gy. The radiotherapy planning of every case had met
      the following conditions: the percentage of total lung volume receiving 20 Gy
      (V20) <=30% and the percentage of total lung volume receiving 30 Gy (V30) <=20%.
      Chemotherapy was commenced on the first day of radiotherapy: NVB 25 mg/m(2), day
      1 and day 8, CBP at AUC of 5 mg/ml(-1).min(-1), day 8, repeated for 28 days, two
      concomitant cycles during radiotherapy, and not more than 4 cycles following
      radiotherapy. A total of 37 patients were recruited and each of them completed
      the entire radiation procedure. No Grade V toxicity was observed within the
      group. The hematological toxicity rates were: Grade III/IV neutropenia was
      observed in 18.9% (7/37) of cases, Grade III/IV thrombocytopenia in 8.1% (3/37)
      of cases, but no cases of Grade III/IV anemia were noted. For non-hematological
      toxicities the rates were: Grade III radiation pneumonitis, 8.1% (3/37) of cases;
      Grade III radiation esophagitis, 13.5% (5/37); but no cases of Grade IV/V non
      hematological toxicities. High-dose 3DCRT also achieved a favorable efficacy: the
      complete response (CR) rate was 13.5% (5/37) and the partial response (PR) rate
      was 64.9% (24/37). The total response (CR+PR) rate was 78.4% (29/37). The median
      survival time was 12 months and the 1-year overall survival rate was 45.1%. Given
      that 35% of patients in the study had stage IV disease, the survival results were
      comparable with other similar studies. In conclusion, in our small-sample
      exploratory study, the high-dose regimen of 70 Gy using 3DCRT with concomitant
      NVB plus CBP was feasible for patients with NSCLC. Further evaluation of this
      regimen is ongoing in a prospective controlled phase II trial.

PMID- 22848248
TI  - Surgical resection using retroperitoneal approach for solitary fibrous tumor in
      the pelvis.
AB  - This report concerns a case of solitary fibrous tumor (SFT) for which surgical
      resection was performed using a retroperitoneal approach. A 41-year-old man was
      referred to our hospital with urinary retention. Abdominal ultrasound sonography
      (US) and computed tomography (CT) showed a hypervascular mass lesion in the
      pelvis. Transrectal biopsy showed SFT. Surgical resection was carried out using a
      retroperitoneal approach and preserving the neural network related to urinary and
      erectile functions. Based on immunohistochemical findings, the tumor was
      diagnosed to be malignant SFT in the pelvic cavity. Urinary function improved
      post-operation. There was no change to IIEF-5 and it continued to function well.
      The patient showed no sign of recurrence 12 months after surgery and required no
      additional therapy.

PMID- 22848249
TI  - Three-gene signature predicts disease progression of non-muscle invasive bladder
      cancer.
AB  - The clinical grades and staging methods currently employed for bladder cancer
      (BC) are inadequate for assessing treatment outcomes for non-muscle invasive
      bladder cancer (NMIBC). We have developed a clinically applicable quantitative
      real-time PCR (qPCR) gene signature to predict the progression of NMIBC. Three
      genes not previously described for BC were selected from our published
      progression-related gene classifier data set. Data were drawn from a previous
      study population and from new cases. Primary NMIBC tissue specimens (n=193) were
      analyzed by qPCR. Risk scores were then used to rank specimens into high- and low
      risk signature groups based on their gene expression. The Kaplan-Meier method and
      a multivariate Cox regression model were used to identify the prognostic value of
      the three-gene signature for both recurrence and progression. The Kaplan-Meier
      estimates revealed significant differences in time-to-recurrence and progression
      between low- and high-risk signatures (log-rank test, p=0.011 and p<0.001,
      respectively). The multivariate Cox regression analysis showed that the three
      gene risk signature is an independent predictor of bladder tumor progression
      (hazard ratio, 4.268; 95% CI, 1.542-11.814; p=0.005). In conclusion, our three
      gene signature was found to be closely associated with progression among patients
      with NMIBC.

PMID- 22848250
TI  - Inhibitory effect of vitamin D-binding protein-derived macrophage activating
      factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived
      carcinoma cell line.
AB  - This study investigated the inhibitory effect of vitamin D-binding protein
      derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth,
      using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch
      carcinogenesis model, as well as the cytocidal effect of activated macrophages
      against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma.
      DMBA application induced squamous cell carcinoma in all 15 hamsters of the
      control group at approximately 10 weeks, and all 15 hamsters died of tumor burden
      within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration
      did not develop tumors and the remaining 12 hamsters showed a significant delay
      of tumor development for approximately 3.5 weeks. The growth of tumors formed was
      significantly suppressed and none of the hamsters died within the 20 weeks during
      which they were observed. When GcMAF administration was stopped at the 13th week
      of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor
      growth was promoted, but none of the mice died within the 20-week period. On the
      other hand, when GcMAF administration was commenced after the 13th week in 5 out
      of the 15 hamsters in the control group, tumor growth was slightly suppressed and
      all 15 hamsters died of tumor burden. However, the mean survival time was
      significantly extended. GcMAF treatment activated peritoneal macrophages in vitro
      and in vivo, and these activated macrophages exhibited a marked cytocidal effect
      on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was
      enhanced by the addition of tumor-bearing hamster serum. These findings indicated
      that GcMAF possesses an inhibitory effect on tumor development and growth in a
      DMBA-induced hamster cheek pouch carcinogenesis model.

PMID- 22848251
TI  - Detection of cathepsin B, cathepsin L, cystatin C, urokinase plasminogen
      activator and urokinase plasminogen activator receptor in the sera of lung cancer
      patients.
AB  - The present study aimed to determine the levels of cathepsin B (cath B),
      cathepsin L (cath L), cystatin C, urokinase plasminogen activator (u-PA) and
      urokinase plasminogen activator receptor (u-PAR) in the sera of patients with
      lung cancer compared to healthy controls using ELISA. Concomitantly, the
      relationship between the components and clinicopathological prognosis was
      analyzed. The study included 30 healthy volunteers and 105 lung cancer patients.
      Blood samples were collected and cath B, cath L, cystatin C, u-PA and u-PAR
      measurements were made using ELISA. Results showed that the levels of cath B,
      cath L, cystatin C, u-PA and u-PAR were significantly higher in the patient group
      compared to the healthy controls. The significance was marked for cath B and mild
      for u-PAR in correlation with lymph node metastasis. There was no significance
      for other parameters. Notably, patients with a combination of high cystatin C and
      high cath B levels had significantly lower survival probability as compared to
      those with cystatin C(+)/cath B(-) or with cystatin C(-)/cath B(-). Similarly,
      patients with a combination of high u-PA and u-PAR experienced significantly
      shorter survival. Furthermore, the univariate analysis revealed that cath B, u
      PAR, lymph node metastases, stage and grade were related to survival. However,
      findings of the multivariate Cox analysis indicated that the sera levels of cath
      B, u-PAR and lymph node metastases may serve as independent prognostic variables
      in patients with lung cancer.

PMID- 22848252
TI  - Prevalence of human papillomavirus in university young women.
AB  - Cervical cancer is the second most prevalent female cancer worldwide. The
      majority of cases appear between the age of 30 and 50. Human papillomavirus (HPV)
      plays a central role in cervical cancer with 99.7% of HPV DNA identified in
      invasive cervical carcinomas. The prevalence of the HPV infection varies
      substantially among countries and according to age and lifestyle. HPV is a common
      sexually transmitted infection among males and females with a 70% higher
      incidence in sexually active females. This study aimed to determine the
      prevalence of human papillomavirus in young university women by analyzing the
      correlation between Papanicolaou (PAP)-stained cervical tests and HPV detection
      by genotyping, as well as other risk factors. A total of 200 women aged between
      18 and 25 years were enrolled in this study, which took place between September
      2008 and May 2009 at the Universidad de Tarapaca, Arica, Chile. Results of the
      PAP smears showed that 97.5% of cells had normal characteristics, although an
      inflammatory pattern was noted. The prevalence of generic HPV infection was 3.5%
      when testing for HPV DNA using the polymerase chain reaction (PCR) method. An
      analysis of the genotype of infected female individuals indicated that high-risk
      HPV types, such as HPV 16 and 31 were present in 42.84 and 14.29% of females,
      respectively, and low-risk types such as HPV 6, in 14.29%. Only one sample with
      differentiated non-HPV (14.29%) was found. A 95% correlation between PAP-stained
      cervical tests and the method of testing for HPV was observed. Using the PCR
      method, it was found that of the 195 negative PAP smears, 5 were positive for HPV
      and two of the samples that were positive for ASC-US were also positive. A
      significantly increased (P<0.05) HPV infection risk was observed in the 18-21 age
      group with a higher prevalence (71.40%) when compared to the 22-25 age group
      (28.6%). A significant (P<0.042) difference was found between smoking and HPV
      infection. In conclusion, a significant (P<0.05) correlation was found between
      PAP and PCR methods for HPV testing in young university women. A significant
      correlation between smoking and HPV was detected, whereas no difference was noted
      with other parameters.

PMID- 22848253
TI  - Expression and significance of p53 and mdm2 in atypical intestinal metaplasia and
      gastric carcinoma.
AB  - Subtypes of intestinal metaplasia may have different manifestations in the
      carcinogenesis of gastric mucosa. The present study aimed to investigate
      expression of murine double minute gene 2 (mdm2) in atypical intestinal
      metaplasia (AIM) and its relationship to gastric carcinoma. Intestinal metaplasia
      (IM) specimens were obtained from 58 cases. Using a novel classification of IM,
      the specimens were classified according to morphological changes exhibited in the
      gastric mucosa; specifically, atypical intestinal metaplasia (AIM) and simple
      intestinal metaplasia (SIM). The gatric carcinoma specimens were then compared
      with types I, II and III IM based on different substances present in the mucous.
      Envision immunohistochemical technique was applied to the detection of the
      expression of p53 and mdm2 in 58 IM and 30 gastric carcinoma cases. Expression of
      both p53 and mdm2 proteins was found to be higher in gastric carcinomas (p53,
      56.67%, 17/30 and mdm2, 53.33%, 16/30) and AIM (p53, 51.85%, 14/27 and mdm2,
      51.85%, 14/27) as compared to SIM (p53, 25.81%, 8/31 and mdm2, 19.35%, 6/31)
      (P<0.05). A similar pattern of expression of mdm2 protein was found in type I
      (36.84%, 7/19), type II (38.46%, 10/26) and type III (23.08%, 3/13) IM and
      gastric carcinoma (53.33%, 16/30). p53 expression was higher in gastric carcinoma
      (56.67%) compared to type I IM (26.32%) (P<0.05). However, no differences were
      evident among type II (42.31%, 11/26), type III (46.15%, 6/13) IM and gastric
      carcinoma. AIM may reveal the precancerous nature of gastric carcinoma more
      clearly than SIM or the conventional IM subtypes. Additionally, AIM may be
      involved as a preneoplastic lesion and therefore be an effective indicator in the
      clinical follow-up of gastric carcinoma patients.

PMID- 22848254
TI  - Growth inhibition and enhanced chemosensitivity induced by down-regulation of
      Aurora-A in human renal cell carcinoma Caki-2 cells using short hairpin RNA.
AB  - The objective of this study was to investigate the inhibitory effects of Aurora-A
      expression on the growth and chemosensitivity of Caki-2 cells in human renal cell
      carcinoma (RCC). Caki-2 cells were established, in which an expression vector
      containing short hairpin RNA (shRNA) targeting Aurora-A was introduced (Caki-2/sh
      A). The growth and sensitivity of chemotherapeutic agents in Caki-2/sh-A cells
      were compared to those in Caki-2 cells transfected with control vector alone
      (Caki-2/C). The expression levels of both Aurora-A mRNA and protein in Caki-2/sh
      A cells were less than 10% of those in Caki-2/C cells. The in vitro growth of
      Caki-2/sh-A cells was significantly inferior to that of Caki-2/C cells, and the
      proportion of Caki-2/sh-A cells in the G2-M phase was significantly greater
      compared to that of Caki-2/C cells. In addition, the expression level of Bax in
      Caki-2/sh-A cells was significantly higher as compared to that in Caki-2/C cells,
      while phosphorylated Akt in Caki-2/sh-A cells was markedly down-regulated
      compared to that in Caki-2/C cells. Among several chemotherapeutic agents
      examined, the most significant difference between Caki-2/sh-A and Caki-2/C cells
      was observed in the sensitivity to docetaxel. Thus, the IC(50) value of docetaxel
      in Caki-2/sh-A cells was decreased by approximately 90% compared to that in Caki
      2/C cells. Treatment of Caki-2/sh-A cells, but not Caki-2/C ones, with 5 nM
      docetaxel resulted in the induction of apoptotic cell death accompanying the
      induction of p53. The findings suggest that the suppression of Aurora-A
      expression using shRNA is a useful therapeutic strategy against RCC through
      growth inhibition as well as enhanced chemosensitivity.

PMID- 22848256
TI  - Aberrant methylation of secreted protein, acidic and rich in cysteine in human
      laryngeal and hypopharyngeal carcinoma.
AB  - Secreted protein, acidic and rich in cysteine (SPARC) has been found to be
      involved in various stages of tumor progression such as migration, invasion,
      extracellular matrix deposition and angiogenesis. To obtain an insight into the
      role of SPARC in the progression of laryngeal and hypopharyngeal carcinoma, we
      investigated SPARC transcription levels and promoter methylation in carcinoma
      cell lines and primary tumors. Reverse transcription-PCR showed that SPARC was
      silenced in laryngeal and hypopharyngeal carcinoma cell lines, in which aberrant
      promoter methylation was detected. Hypermethylation of SPARC was detected in
      56.1% (23/41) of laryngeal carcinoma and 70.0% (7/10) of hypopharyngeal carcinoma
      biopsies, but only in 11.1% (1/9) of normal epithelial specimens by a methylation
      specific PCR assay. Bisulphite genomic sequencing indicated that CpG sites in the
      SPARC promoter were heavily methylated in cell lines and primary tumors.
      Moreover, pharmacological demethylation treatment rescued SPARC expression with 5
      aza-2'-deoxycytidine (5-aza-dC) in the laryngeal carcinoma cell lines. SPARC
      promoter hypermethylation was significantly correlated with lymph node metastasis
      (p<0.01). Our findings suggest that hypermethylation of SPARC is a frequent and
      tumor-specific event in laryngeal and hypopharyngeal carcinomas and may serve as
      a biomolecular marker for diagnosis and prognosis.

PMID- 22848255
TI  - EPAS1 mRNA in plasma from colorectal cancer patients is associated with poor
      outcome in advanced stages.
AB  - The presence of free nucleic acids in plasma has been detected in cancer patients
      and is associated with poor prognosis. In the present study, the mRNA levels of
      three genes (EPAS1, KIAA0101 and UBE2D3) in plasma from colorectal cancer
      patients were analyzed. These genes were selected from a previous study of
      genomic profiles, discriminating between healthy controls and colorectal cancer
      patients. mRNA levels were analyzed by real-time PCR in the plasma of 154
      patients with colorectal cancer. The association of plasma mRNA levels with
      clinicopathological parameters and patient survival were analyzed. High levels of
      EPAS1 in the plasma were associated with patients aged over 50 years, relapse of
      disease and patient mortality. When patients were divided into two groups, early
      (I and II) and advanced (III and IV) stages, an association was observed between
      high levels of EPAS1 mRNA and worse disease-free and overall survival in advanced
      stages. The expression of KIAA0101 and UBE2D3 was not associated with poor
      prognosis. Thus, our results suggest that EPAS1 mRNA levels may be an indicator
      of poor prognosis in colorectal cancer patients at advanced stages, obtained by a
      non-invasive method.

PMID- 22848257
TI  - Survival of untreated advanced colorectal cancer patients.
AB  - Colorectal cancer has specific biological characteristics that distinguish it
      from other malignancies. One such characteristic is its slow growth in patients
      in advanced stages. For the past 15 years, no effective systemic treatment has
      been available in clinical practice. The present study involved a retrospective
      evaluation of patients with advanced colorectal cancer in order to assess the
      median and overall survival of patients. Concurrently, the study aimed to
      describe the biological characteristics of this slow-growing disease and the
      quality of life of the patients. The key characteristic of this patient group was
      the lack of any systemic treatment. The study included 40 patients (25 male and
      15 female, median age 67 years) who were evaluated between 1993 and 1996. Only
      supportive treatment was provided. One patient underwent 2 cycles of
      chemotherapy. Liver surgery was unsuccessfully performed on 3 patients. Two
      patients underwent radiofrequency once and 2 had intra-arterial treatment, also
      once. The results showed the median survival of patients to be 24 months (range
      16-42). One-year survival was found to be 65% while the 2-year survival was found
      to be 25%. A satisfactory quality of life was also observed. In conclusion,
      colorectal cancer is a slow-going malignancy, as indicated by the long-term
      survival of patients and the biological characteristics of the tumor.

PMID- 22848258
TI  - The neutrophil/lymphocyte ratio is an independent prognostic indicator in
      patients with bone metastasis.
AB  - Patients with the most common advanced human cancers such as lung, breast,
      uterus, and cancers of the digestive system almost always develop bone
      metastases, with painful and untreatable consequences. This study aimed to
      determine the prognostic implications of the neutrophil/lymphocyte (N/L) ratio in
      the peripheral blood of patients with malignant bone metastasis. Study
      participants were identified from a prospective cohort of cancer patients with
      bone metastasis. Data for the N/L ratios were obtained from clinical and
      pathological records and were analyzed together with other known prognostic
      factors in the multivariate and univariate analyses. The results showed the
      average N/L ratio of all 497 patients to be 4.25+/-2.44 (range 0.54-45.50 years).
      Multivariate analysis revealed that tumor type and a high N/L ratio were
      significantly associated with poor prognosis. For the high N/L ratio group, the
      estimated hazard ratio of death was 1.348 [95% confidence interval (CI), 1.062
      1.712] compared with the low N/L ratio group. The average N/L ratio of the 225
      patients in the surgery group was 2.79+/-2.46 (range 0.77-22.75 years).
      Multivariate analysis revealed that a preoperatively high N/L ratio (P=0.013;
      HR=2.945; 95% CI, 1.256-6.906) was significantly associated with poor prognosis
      after bone metastasis in the surgery group. In conclusion, the N/L ratio was
      confirmed to be an independent prognostic factor in patients with bone
      metastasis. Thus, the N/L ratio may serve as a clinically accessible and useful
      biomarker for patient survival.

PMID- 22848259
TI  - Sinomenine inhibits proliferation of SGC-7901 gastric adenocarcinoma cells via
      suppression of cyclooxygenase-2 expression.
AB  - Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal
      plant Sinomenium acutum. Results of studies have shown that the anti
      inflammatory, immunosuppressive and anti-arthritic effects of SIN are partially
      attributed to the inhibition of cyclooxygenase-2 (COX-2) expression. COX-2
      overexpression is associated with enhanced proliferation and angiogenesis of
      gastric cancer (GC). SGC-7901 cells were treated with different concentrations of
      SIN in order to observe its effect on the proliferation of human gastric
      adenocarcinoma cells and to explore the potential underlying molecular mechanism
      via the detection of COX-2 expression. Celecoxib was used as the positive
      control. Morphological alterations of the cells were observed microscopically.
      Cell proliferation was evaluated using MTT assay. COX-2 expression was detected
      using semi-quantitative RT-PCR and Western blotting. The results showed that SIN
      inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent
      manner. In the presence of SIN or celecoxib, SGC-7901 cells became round and
      detached morphologically, indicating cell apoptosis. The expression of COX-2 was
      inhibited by SIN in a dose-dependent manner at both the mRNA and protein levels.
      Our findings indicate that the protective effects of SIN are mediated through the
      inhibition of COX-2 expression. These findings suggest a novel therapy to treat
      inflammation-mediated gastric adenocarcinomata.

PMID- 22848260
TI  - Comparative evaluation of surgical stress of laparoscopically assisted vaginal
      radical hysterectomy and lymphadenectomy and laparotomy for early-stage cervical
      cancer.
AB  - The aim of this study was to objectively evaluate the benefits of
      laparoscopically assisted vaginal radical hysterectomy and lymphadenectomy for
      early-stage cervical cancer. Clinical data were prospectively collected from
      patients with IA-IIB cervical cancer who underwent laparoscopically assisted
      vaginal radical hysterectomy (n1=33) and laparotomy (n2=30). Peripheral blood
      samples were obtained prior to surgery and at 1 and 2 h into the operation, as
      well as on days 1, 4 and 7 following surgery to measure serum interleukin-6, C
      reaction protein and cortisol. Results showed that there was no conversion to
      laparotomy in the laparoscopy group. The average blood loss was 317.23+/-217.20
      ml (laparoscopy group) and 872.58+/-693.16 ml (laparotomy group). No significant
      difference was found in the number of resected pelvic lymph nodes (19.74+/-7.43
      in the laparoscopy group and 20.35+/-6.62 in the laparotomy group). At days 1 and
      7 after surgery, the serum IL-6 level was significantly different in the
      laparoscopy and laparotomy groups (day 1: laparoscopy group 17.14+/-16.53 pg/ml
      and laparotomy group 34.32+/-20.97 pg/ml, p=0.001; day 7: laparoscopy group 6.7+/
      7.21 pg/ml and laparotomy group 17.54+/-16.47 pg/ml, p=0.001). The serum CRP
      level was significantly different at days 1 and 7 after the operation (day 1:
      laparoscopy group 7024.72+/-949.12 ng/ml and laparotomy group 7586.61+/-869.42
      ng/ml, p=0.018; day 7: laparoscopy group 4357.71+/-2108.85 ng/ml and laparotomy
      group 6967.96+/-995.02 ng/ml, p<0.001). A significant difference was noted in the
      serum cortisol level at day 4 after the operation (122.29+/-65.17 ng/ml in the
      laparoscopy group and 186.76+/-68.61 ng/ml in the laparotomy group, p<0.001). In
      conclusion, the differences in clinical data and the various parameters pertinent
      to surgical stress evaluated in this study suggest that laparoscopic surgery for
      cervical cancer causes less postoperative stress than conventional open surgery.

PMID- 22848261
TI  - Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered
      CD20-specific T cells.
AB  - Adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell
      receptors is a promising approach to lymphoma therapy. However, modification of
      the cellular signaling pathways in target tumor cells by treatment with
      engineered CD20-specific T cells has yet to be fully elucidated. In this study,
      the non-Hodgkin's lymphoma Raji cell line was co-cultured with T cells that were
      genetically modified with anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene.
      The cytolytic activity of engineered CD20-specific T cells and IL-10 secretion
      was quantitated by Cytotoxicity and ELISA assays, respectively. The engineered
      CD20-specific T cells and Raji cells were sorted using flow cytomety for the
      Western blot analysis. Treatment of Raji cells with T cells genetically modified
      with anti-CD20scFvFc/CD28/CD3zeta chimera (compared to anti-CD20scFvFc) yielded a
      higher cytotoxicity against Raji cells in vitro. Additionally, we found that
      engineered CD20-specific T cells caused a decrease in IL-10 secretion and
      inhibition of phosphor-STAT3 and Bcl-2 expression in Raji cells, possibly through
      the down-regulation of p38 MAPK and NF-kappaB activity. These results indicate
      that the treatment of Raji cells with engineered CD20-specific T cells inhibited
      the cellular p38 MAPK signaling pathways, which enhanced its antitumor activities
      against CD20-positive tumor cells.

PMID- 22848262
TI  - The role of miR-26 in tumors and normal tissues (Review).
AB  - miR-26, a functional miRNA, has received much attention from researchers in
      recent years. miRNAs may play crucial roles in numerous biological processes such
      as cell proliferation, apoptosis, tumorigenesis at different stages of non-tumor
      diseases, growth and development of normal tissues, and other biological
      processes. The expression of miR-26 has been found to be specific to different
      biological processes. Furthermore, its expression is frequently abnormal in
      tumors, indicating that miR-26 may play significant roles in tumor formation.
      Various reports exist regarding miR-26 involvement in non-tumor diseases, as well
      as the process of growth and development of normal tissues. In this review, we
      report findings of recent studies on the expression of miR-26 in different types
      of diseases and the process of growth and development and its predicted target
      genes in different tissue types. In conclusion, it is useful for researchers to
      understand the role of miR-26 in different biological processes.

PMID- 22848264
TI  - Pharmacokinetic and pharmacodynamic profiles of subcutaneous administration of
      continuous erythropoietin receptor activator in lung cancer patients with anemia
      induced by chemotherapy.
AB  - Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative
      erythropoiesis-stimulating agent with unique erythropoietin receptor activity and
      a prolonged half-life. C.E.R.A. is currently in development for the correction of
      anemia and stable hemoglobin (Hb) control at extended administration intervals in
      patients with cancer who are receiving chemotherapy. The purpose of this
      pharmacological study was to evaluate the pharmacokinetic (PK), pharmacodynamic
      (PD) and safety profiles of C.E.R.A. administered subcutaneously once every 3
      weeks (Q3W) in lung cancer patients with anemia induced by chemotherapy. This
      open-label, multicenter study recruited 46 patients. Entry Hb levels were not
      more than 11.0 g/dl. Five dose levels of C.E.R.A. (2.1, 4.2, 6.3, 9 and 12
      MUg/kg) were tested in sequential cohorts of 8-11 patients for 12 weeks. The mean
      values for C.E.R.A half-life ranged from 143 to 247 h. The maximum serum
      concentration (C(max)) following the first administration of C.E.R.A. increased
      in proportion to the dose. The increase of Hb levels occurred in a dose-dependent
      manner. No serious adverse events reported as being related to C.E.R.A. were
      observed during the study period. Thrombovascular events were not observed in any
      patient. Anti-C.E.R.A antibodies were not detected in any patient. Thus, this
      pharmacological study confirmed the long half-life of C.E.R.A., thereby
      supporting subcutaneous administration of C.E.R.A. at the Q3W interval. PK and PD
      parameters demonstrated dose-proportionality over the range of doses tested in
      this study. Additionally, C.E.R.A. was generally well tolerated.

PMID- 22848263
TI  - Fascin expression in dendritic cells and tumor epithelium in thymoma and thymic
      carcinoma.
AB  - The majority of thymomas are histologically characterized by tumor-infiltrating
      lymphocytes. Mature dendritic cells (DCs) are known to assemble lymphocytes
      through antigen presentation to T lymphocytes. Fascin, a 55-kDa actin-binding
      protein and a known marker for mature DCs, regulates filaments necessary for the
      formation of filopodia in cell migration. Moreover, fascin expression in various
      epithelial neoplasms has recently been reported to be associated with invasion of
      tumor cells and clinically aggressive manifestations. In the present study, we
      investigated fascin expression immunohistochemically in tissues of thymomas and
      thymic carcinomas surgically resected at our institute. A total of 34 thymomas
      and 5 thymic carcinomas were included. The amount and immunohistochemical
      intensity of both fascin(+) DCs and tumor epithelium were counted and assessed,
      and the clinicopathological data were also scored. Statistical analyses revealed
      that the amount of fascin(+) DCs with the formation of clusters was associated
      with lymphocyte-rich variants (p=0.002) and cortical differentiation (p=0.037) of
      thymoma with complication from myasthenia gravis (p=0.002). The quantity of
      fascin(+) epithelium was associated with a strong intensity of fascin in
      infiltrating DCs (p=0.002) with the formation of clusters (p=0.002) and favorable
      prognosis, as assessed by the Masaoka staging system (p=0.001). The amount of
      infiltrating DCs (p=0.024) and fascin(+) epithelium were lower in thymic
      carcinoma. It was concluded that fascin(+) epithelium may induce tumor immunity
      through the surveillance activity of fascin(+) DCs in thymic neoplasms, thus
      improving prognosis.

PMID- 22848265
TI  - Expression of hepatocyte markers in mass-forming peripheral and periductal
      infiltrating hilar intrahepatic cholangiocarcinomas.
AB  - In this study, the expression of hepatocyte markers, including alpha-fetoprotein
      (AFP), HepPar-1 antigen and arginase-1, was examined immunohistochemically in 14
      mass-forming peripheral intrahepatic cholangiocarcinomas (ICCs) that arose from
      the peripheral portion of the biliary tree, and in 14 periductal-infiltrating
      hilar ICCs that arose from intrahepatic large bile ducts. Only 2 (14.3%) of the
      14 hilar ICCs and 2 (14.3%) of the 14 peripheral ICCs expressed AFP or HepPar-1
      antigen. Conversely, arginase-1 was expressed in 8 (57.1%) and 11 (78.6%) of the
      hilar and peripheral ICCs, respectively, and 4 (28.6%) hilar ICCs and 7 (50%)
      peripheral ICCs expressed arginase-1 in more than 10% of the cancer cells. The
      expression of arginase-1 did not differ between peripheral ICCs showing major
      histology of poorly differentiated adenocarcinoma and those showing other major
      histologies, including well-or moderately differentiated tubular adenocarcinoma
      or papillary adenocarcinoma. Results of the present study showed that common
      hepatocyte markers, including AFP and HepPar-1 antigen, are rarely but definitely
      expressed in hilar and peripheral ICCs, and that a third hepatocyte marker,
      arginase-1, is expressed at a high rate in both hilar and peripheral ICCs,
      irrespective of their histology. These results indicate that care should be taken
      when using arginase-1 as a hepatocyte marker for distinguishing between a poorly
      differentiated hepatocellular carcinoma and a mass-forming peripheral ICC showing
      the histology of poorly differentiated adenocarcinoma.

PMID- 22848266
TI  - Matrix metalloproteinase 3 is a stromal marker for chicken ovarian cancer.
AB  - Matrix metalloproteinases (MMPs) are involved in the degradation of the
      extracellular matrix and basement membranes. Due to this, MMPs have been thought
      to promote invasion and metastasis of cancer cells and angiogenesis in tumors.
      Even though the chicken is a useful animal model for studying human ovarian
      cancer, no reports exist of the MMP expression pattern in chicken ovarian cancer.
      Therefore, we investigated the expression pattern of MMPs in chicken ovarian
      cancer. Results of RT-PCR and quantitative RT-PCR analyses showed MMP3 to be over
      expressed in cancerous hen ovaries. In situ hybridization analysis of cancerous
      chicken ovaries showed that MMP3 mRNA was predominantly localized in the stroma,
      which is similar to MMP3 expression in human cancers. The results suggest that
      the expression pattern of MMP3 mRNA in chicken ovarian cancer is similar to that
      in various types of human cancer. Moreover, MMP3 potentially plays a significant
      role in developing ovarian cancer in chickens. The cell type-specific expression
      of MMP3 makes this gene a unique marker for ovarian cancer in chickens.

PMID- 22848267
TI  - Differential efficacy of docetaxel according to non-small cell lung cancer
      histology and the therapeutic effect of epidermal growth factor receptor tyrosine
      kinase inhibitors.
AB  - The active mutation of epidermal growth factor receptor (EGFR) and clinical
      characteristics are significant biomarkers for chemotherapy selection in non
      small cell lung cancer (NSCLC). Although docetaxel is a key agent in second-line
      therapy for NSCLC, predictive biomarkers for assessing its efficacy have yet to
      be determined. To assess the clinical efficacy of docetaxel in second-line
      therapy for NSCLC according to NSCLC histology and the therapeutic effect of EGFR
      tyrosine kinase inhibitors (EGFR-TKIs), we retrospectively reviewed 454 NSCLC
      patients treated with docetaxel between April 2002 and April 2009. In total, 239
      patients with advanced NSCLC treated with docetaxel as second-line therapy
      following failure of platinum-based chemotherapy were analyzed in this study. A
      total of 59 (25%) patients had squamous cell carcinoma. The overall response rate
      and median progression-free survival time in the squamous cell group were
      significantly inferior to those in the non-squamous cell group (p=0.031 and
      p=0.005, respectively). Following the failure of docetaxel, 91 non-squamous
      patients were treated with EGFR-TKIs. The patients that achieved clinical benefit
      from EGFR-TKIs (n=32) demonstrated a significantly better response rate and
      longer progression-free survival compared to the other group (p<0.001 and
      p=0.027, respectively). In the univariate and multivariate analysis, the
      favorable therapeutic effect of EGFR-TKIs had an independent effect on
      progression- free survival (HR 1.484, p=0.0464). In conclusion, this
      retrospective study suggests that non-squamous histology and favorable
      therapeutic effect from EGFR-TKIs are useful markers for predicting the efficacy
      of docetaxel in second-line therapy for NSCLC.

PMID- 22848268
TI  - CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer.
AB  - Stem cells are thought to contribute to tissue regeneration as well as
      carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC) has
      shown distinct characteristics compared with those of sporadic CRC. The aim of
      this study was to evaluate the expression of stem cell markers CD133, OCT4 and
      NANOG in UC-CRC and the inflamed colonic epithelium of UC patients. Total RNAs of
      UC-CRC (n=6), inflamed colonic epithelium (n=24), sporadic CRC (n=37) and
      adjacent normal colonic epithelium (n=37) were isolated from formalin-fixed,
      paraffin-embedded specimens using microdissection techniques in order to purify
      colonic epithelial cells. Relative mRNA levels of CD133 (PROM), OCT4 (POU5F1) and
      NANOG were measured using real-time reverse transcription polymerase chain
      reaction. Three stem cell markers were also investigated immunohistochemically.
      PROM, POU5F1 and NANOG levels were found to be significantly lower in UC-CRC than
      in inflamed colonic epithelium of UC patients. By contrast, sporadic CRC showed a
      significantly higher expression of PROM, POU5F1 and NANOG compared with adjacent
      normal colonic epithelium. POU5F1 and NANOG levels were significantly lower in UC
      CRC than in sporadic CRC. PROM and NANOG levels in inflamed colonic epithelium
      were significantly higher among younger UC patients (P<0.05). Longer disease
      duration was significantly associated with lower PROM expression (P=0.0117). No
      significant difference was found in PROM levels between UC-CRC and inflamed
      colonic epithelium in patients with longer disease duration. UC-CRC showed
      different expression profiles of stem cell markers compared with sporadic CRC.
      Decreases in PROM expression of inflamed colonic epithelium may identify UC
      patients at high risk for the development of UC-CRC.

PMID- 22848269
TI  - Gastric cavernous hemangioma: A rare case with upper gastrointestinal bleeding.
AB  - Upper gastrointestinal bleeding caused by a gastric hemangioma is a relatively
      rare occurrence. We report the case of a 65-year-old woman who suffered a sudden
      onset of hematemesis. Endoscopy revealed a 4*3 cm mass located in the gastric
      fundus. Abdominal contrast-enhanced CT revealed the shadow of enhancing linear
      blood vessels located in the gastric fundus. Based on her clinical appearance and
      the laboratory results, the patient was diagnosed with gastric hemangioma. In the
      laparotomy, a proximal gastrectomy was performed. The final diagnosis of
      cavernous hemangioma arising from the gastric fundus was confirmed by
      postoperative pathological examination.

PMID- 22848270
TI  - Trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from
      parous MMTV-erbB-2 transgenic mice.
AB  - erbB-2 is amplified or overexpressed in approximately 30% of human breast
      cancers, and has been associated with poor prognosis and therapeutic resistance.
      Previous studies have suggested that erbB-2 overexpression in transgenic mice
      induces genomic instability; however, the patterns of genetic lesions vary with
      individual model systems. The development of mammary tumors in multiparous murine
      mammary tumor virus (MMTV)-erbB-2 transgenic mice is accelerated due to hormonal
      interactions which induce the overexpression of MMTV-mediated erbB-2. However,
      whether or not accelerated tumor development is associated with modified
      cytogenetic patterns remains to be determined. In this study, chromosomal changes
      were characterized in mammary tumor cells derived from multiparous MMTV-erbB-2
      transgenic mice, and compared with tumor cells derived from control virgin mice.
      Immunohistochemistry and Western blotting were used to detect erbB-2
      overexpression in mammary tissues. Each of the five tumors from the multiparous
      MMTV-erbB-2 transgenic mice was found to exhibit a marked chromosomal imbalance,
      compared with only one tumor with aberrant chromosomes among the five tumors from
      the control virgin mice. In particular, trisomy 5 and loss of the X chromosome
      were recurrent cytogenetic lesions in tumors from the parous mice, which is a
      novel pattern compared with previous studies. The elevated number of genetic
      lesions in tumors from parous mice, which were characterized by enhanced erbB-2
      overexpression and increased receptor tyrosine kinase activation in the mammary
      glands, suggest a causal role for erbB-2 in the genomic instability present in
      these tumors. These data advance our understanding of erbB-2-mediated
      pathogenesis and underscore the role of cytogenetic alteration in this process.

PMID- 22848271
TI  - Fusion between cancer cells and myofibroblasts is involved in osteosarcoma.
AB  - Communication between cancer cells and the microenvironment appears to be an
      important determinant of disease prognosis. However, the detailed mechanisms of
      the interactions between cancer cells and surrounding cells have yet to be
      clarified. Recent studies on cell fusion have indicated this interaction to be
      one of the driving forces in cancer progression. Fibroblasts constitute a
      significant component of the carcinoma stromal compartment. Many of these
      fibroblasts are thought to differentiate into myofibroblasts, which are
      characterized by a positive expression of alpha-smooth muscle actin. Expression
      of alpha-smooth muscle actin in osteosarcoma was evaluated, and was observed to
      be excessive in the multinucleated osteoclast-like giant cells in osteosarcoma
      tissue, indicating the possibility of cell fusion between cancer cells and
      myofibroblasts. In order to test the above hypothesis, we first transformed the
      primary mouse embryonic fibroblast cells into activated myofibroblast cells.
      Osteosarcoma cells were then co-cultured with mouse myofibroblast cells, and cell
      fusion was investigated using species-specific chromosomal markers. Expression of
      alpha-smooth muscle actin was successfully induced in primary mouse embryonic
      fibroblast cells. Cells fused spontaneously with a fusion rate of approximately 1
      2% and fusion between more than two cells was also observed. Our study
      demonstrated that fusion between cancer cells and myofibroblasts may contribute
      to the observed multinucleated giant cells in osteosarcoma. We posit that cell
      fusion is a novel mechanism for the interaction between cancer cells and the
      microenvironment.

PMID- 22848272
TI  - Evidence for PTEN-independent Akt activation and Akt-independent p27(Kip1)
      expression in advanced bladder cancer.
AB  - In the treatment of advanced bladder cancer (BC), attention has recently focused
      on small molecule therapy concerning EGFR and the downstream Akt signalling
      pathway. Cellular deregulation processes are poorly understood, and biological
      determinants for the selection of therapy and monitoring are currently not
      available. The proteins PTEN, p-Akt and p27(Kip1) are suggested to be potentially
      significant biomarkers of Akt signalling. In this study, we investigated the
      expression of these proteins in advanced BC. PTEN, p-Akt and p27(Kip1) expression
      was determined immunohistochemically in 86 T2-4 BC specimens using a tissue
      microarray technique. Staining was documented with regard to intensity, cellular
      frequency and a multiplied staining score. Staining characteristics of the three
      proteins were correlated by regression analysis with the parameters of tumour
      stage and grade. A positive correlation was observed in the expression scores of
      PTEN and p-Akt, p-Akt and p27(Kip1) as well as PTEN and p27(Kip1) (p<0.02 for all
      combinations). The positive correlation between PTEN and p-Akt resulted mainly
      due to the strong correlation of PTEN intensity with p-Akt (p=0.0003 and p=0.0006
      to p-Akt frequency and intensity, respectively). A positive correlation between p
      Akt and p27(Kip1) was noted for p-Akt frequency as well as intensity (p<0.05 for
      all combinations). The positive correlation between PTEN and p27(Kip1) resulted
      due to the correlation of PTEN intensity alone with p27(Kip1) (p<0.03 for
      p27(Kip1) frequency and intensity), whereas no significance was noted for PTEN
      frequency. No correlation was found between T or G and expression of the
      proteins. However, activation of Akt in BC is known to occur independently of
      PTEN protein loss and appears not to cause a decrease of p27(Kip1). However, a
      direct regulatory impact of PTEN on p27(Kip1) was found. PTEN intensity, rather
      than frequency, appears to be a superior biomarker. These results may provide
      information to support research into protein profiling-predicted targeted therapy
      for BC. Correlations to benign urothelium, superficial BC specimens and follow-up
      data remain to be investigated.

PMID- 22848274
TI  - Elevated microRNA-126 is associated with high vascular endothelial growth factor
      receptor 2 expression levels and high microvessel density in colorectal cancer.
AB  - MicroRNAs (miRNAs) are involved in a number of biological processes, including
      tumour biology. Pre-clinical studies have shown that miRNA-126 regulates
      signalling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2)
      and, consequently, angiogenesis. The aim of this study was to analyse the
      possible relationship between miRNA-126, VEGFR-2 and angiogenesis in tumour
      tissue from patients with colorectal cancer (CRC). Tumour tissue was obtained
      from 81 patients. The miRNA-126 and VEGFR-2 gene expression levels were analysed
      by PCR and the protein concentrations of VEGFR-2 were analysed by ELISA.
      Angiogenesis, visualised by the endothelial cell marker CD105 combined with
      caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD)
      technique. In situ hybridisation was performed for miRNA-126. Tumours were
      classified as low or high miRNA-126-expressing using the median as the cut-off.
      The median gene expression levels of VEGFR-2 were significantly lower in the
      tumours expressing low levels of miRNA-126, 0.30 (95% CI, 0.24-0.36), compared to
      those expressing high levels of miRNA-126, 0.48 (95% CI, 0.28-0.60), p=0.02. A
      positive association was observed with VEGFR-2 protein concentrations, p=0.06.
      The median MVD was significantly lower in the tumours expressing low levels of
      miRNA-126, 5.8 (95% CI, 5.33-6.67), compared to those expressing high levels, 8.0
      (95% CI, 6.33-9.00), p<0.01. miRNA-126 was detected in endothelial cells by in
      situ hybridisation analysis. These results suggest that high levels of miRNA-126
      in CRC are associated with high VEGFR-2 mRNA and protein levels and a higher
      density of newly formed microvessels. However, further studies should be
      conducted to analyse the clinical value of miRNA-126 in CRC.

PMID- 22848273
TI  - High-level expression of stem cell marker CD133 in clear cell renal cell
      carcinoma with favorable prognosis.
AB  - The cancer stem cell (CSC) model suggests that high levels of CSCs within a tumor
      are associated with poor prognosis. The aim of this study was to investigate the
      expression of the stem cell marker CD133 in clear cell renal cell carcinoma
      (ccRCC), and its prognostic significance. The expression of CD133 was examined in
      140 cases of ccRCC using immunohistochemistry. Ki-67 and Oct-4 were double
      immunostained with CD133 to evaluate the proliferative activity and the stemness
      of CD133-expressing cells, respectively. CD133 expression was observed in 45
      cases (32.1%) and high levels of expression were found to be associated with a
      macro-/microcystic pattern, non-sarcomatoid changes and non-metastatic disease.
      The Ki-67 labeling index tended to be lower in CD133-expressing ccRCCs compared
      to non-expressing tumors. CD133-expressing tumor cells rarely expressed Oct-4. A
      high degree of CD133 expression was observed in ccRCC with more differentiated
      morphology and non-metastatic disease, suggesting that CD133 is a favorable
      prognostic marker. These results also indicate that CD133 as a single marker may
      not be sufficient for CSC identification in ccRCC and, therefore, more specific
      CSC markers should be developed.

PMID- 22848275
TI  - Primary retroperitoneal malignant melanoma: A case report.
AB  - Primary malignant melanoma occurring at an extra cutaneous site is rare. A case
      of primary malignant melanoma located in the retroperitoneum of an 18-year-old
      female is presented in this study. Histopathological examination of the tissue
      biopsies at laparotomy with immunohistochemical stains confirmed a diagnosis of
      malignant melanoma. Further extensive clinical and radiological investigations
      proved the retroperitoneum to be the primary site.

PMID- 22848276
TI  - Acquisition of selective antitumoral effects of recombinant adeno-associated
      virus by genetically inserting tumor-targeting peptides into capsid proteins.
AB  - Recombinant adeno-associated virus serotype 5 (rAAV5) is considered to be a
      promising gene transfer vehicle. However, preferential gene delivery to the tumor
      remains a requirement for cancer treatment. We generated rAAV5 mutants bearing
      tumor marker-binding peptides and analyzed their properties as viral vectors, as
      well as their transduction efficiencies and preferential antitumoral potencies.
      All of the mutants were successfully produced. Transduction analyses showed that
      rAAV5 mutants harboring tumor-homing peptides, including RGD and TnC, transduced
      human cancer cells expressing corresponding receptors on their surfaces. RGDS
      peptides and TnC antibodies significantly suppressed transduction by rAAV5-RGD
      and rAAV5-TnC. Cytotoxicity was evident upon transfer of HSV-TK to cells by re
      targeted rAAV5. These results provide evidence that rAAV5 vectors, genetically
      armed with tumor-targeting ligands, preferentially infect human cancer cells
      harboring the corresponding receptors, thereby inducing antitumoral effects.
      Further optimization of rAAV5 mutant viruses should thus facilitate practical
      exploitation of these vectors for gene-based cancer treatment.

PMID- 22848277
TI  - RNAi targeting of hTERT gene expression induces apoptosis and inhibits the
      proliferation of lung cancer cells.
AB  - The present study aimed to investigate the effects of RNAi-mediated reduction in
      human telomerase reverse transcriptase (hTERT) expression on apoptosis and lung
      cancer cell proliferation. A number of cell lines, including 95D, were used.
      hTERT mRNA levels were detected, and the RNA concentration was calculated. MTT
      assay was used to detect the inhibition of cell proliferation. The siRNA with the
      highest suppression rate, siRNA-1, was transfected into 95D cells at three
      different concentrations (50, 80 and 100 nmol/l). The levels of hTERT mRNA in
      cells transfected with 50 nmol/l siRNA-1 were not significantly different from
      those of the negative control-transfected cells (P>0.05), whereas both 80 and 100
      nmol/l siRNA-1 showed significant reductions in hTERT mRNA compared to the
      negative control cells (P<0.01). hTERT levels in the 80- and 100-nmol/l groups
      were not significantly different (P>0.05). Compared with the control cells, cells
      transfected with 50, 80 or 100 nmol/l siRNA-1 showed higher fractions of
      apoptotic cells 48 h post-transfection (P<0.01), although the apoptotic fraction
      in cells transfected with 50 nmol/l siRNA-1 was not significantly different
      compared to that in cells transfected with negative control siRNAs (P>0.05).
      Moreover, the 80- and 100-nmol/l-transfected cells showed significantly increased
      apoptotic indices (P<0.01). MTT results indicated a time-dependent inhibition of
      siRNA-1- transfected cell proliferation starting at 12 h and lasting through 48 h
      post-transfection; the inhibition was attenuated by 72 h post-transfection. The
      high levels of hTERT mRNA in all human lung cancer cell lines tested suggest that
      telomerase plays a role in lung carcinogenesis, and this hypothesis was
      strengthened by the data showing that the siRNA-mediated reduction in hTERT mRNA
      caused apoptosis and an inhibition of the proliferation of lung cancer cells.

PMID- 22848278
TI  - Elevated expression of solute carrier family 22 member 18 increases the
      sensitivity of U251 glioma cells to BCNU.
AB  - Previous studies showed that solute carrier family 22 member 18 (SLC22A18) is
      involved in tumorigenesis. The aim of this study was to examine the role of
      SLC22A18 in glioma cells. Glioma U251 cells were transfected with the human
      SLC22A18 gene. Transfection of the empty vector pcDNA3.1 was used as a negative
      control. Sensitivity to BCNU was measured by Annexin V staining. The expression
      of caspase-3 and bcl-2 was determined by immunohistochemistry. The transfection
      was confirmed by PCR, RT-PCR and Western blotting. Augmented apoptotic cell death
      was observed in the SLC22A18-transfected cells, compared to the non-transfected
      cells or cells with the empty vector. Caspase-3 expression increased in U251
      SLC22A18 cells, whereas the bcl-2 expression decreased. These results indicated
      that SLC22A18 has a pro-apoptotic function in glioma cells.

PMID- 22848279
TI  - Vascular endothelial growth factor-A and changes in a tumor-bearing mouse model
      with Lewis lung cancer.
AB  - Vascular endothelial growth factor-A (VEGF-A) affects tumor growth and metastasis
      through stimulation of angiogenesis. The purpose of this study was to describe
      features of Lewis lung cancer (LLC) in mice and compare the serum VEGF-A levels
      with those of normal control mice. Two groups of mice were compared: one was
      subcutaneously injected with LLC cells (n=16) and the other served as the normal
      control (n=6). The serum VEGF-A levels were measured by ELISA prior to
      inoculation, and at 7, 21 and 35 days post-inoculation. The tumor weight and the
      metastatic condition were evaluated on day 35. Changes in body weight and serum
      VEGF-A concentration over a period of time were compared between the groups using
      generalized estimating equations. The relationship between the primary tumor and
      the metastatic condition was analyzed using the Spearman's rank correlation test.
      The survival rate was 56.3% on day 35 post-tumor inoculation. No difference was
      found between the groups with regard to gastrocnemius muscle weight on day 35
      post-inoculation [0.1315+/-0.0066 g vs. 0.1308+/-0.0069 g (normal control)]. In
      tumor-bearing mice, the weight gain at sacrifice was less (0.24+/-0.45 vs. 1.93+/
      0.47 g, P=0.01), the final mean tumor volume and weight were 4264.69+/-1038.32
      mm(3) and 3.70+/-0.83 g, the number of nodules in the lungs and livers was 6.33
      (range 0-20) and 2.22 (range 0-11), respectively, and the serum VEGF-A levels
      were significantly higher than those of control mice. In conclusion, lower body
      weight gain, metastasis in the liver and lungs, and elevated VEGF-A levels are
      features of LLC in mice.

PMID- 22848280
TI  - Expression of GLUT1 is associated with increasing grade of malignancy in non
      invasive and invasive urothelial carcinomas of the bladder.
AB  - Glucose Transporter 1 (GLUT1) belongs to the expanding mammalian facilitative
      glucose transporter family. Elevated GLUT1 protein expression has been observed
      in the majority of urothelial carcinomas, with various effects on
      clinicopathological parameters. Whereas malignant cells have an accelerated
      metabolism with increased energy requirements, the membranous expression of GLUTs
      is amplified. GLUT1 protein expression was evaluated in urothelial tumours of
      increasing grade of malignancy, supplemented by a tumour proliferation analysis.
      Particular attention was paid to non-invasive precursors of urothelial carcinoma.
      A total of 105 paraffin-embedded samples were classified (normal urothelium,
      low/high-grade papillary carcinoma, carcinoma in situ and invasive carcinoma).
      Grading and staging were conducted using the 1998 ISUP/2004 WHO criteria. The
      staining intensity of GLUT1 was assessed with a standard immunoreactive score
      (IRS). The Ki-67 index was assessed by counting positive nuclei in representative
      urothelial hot spots. Results showed that an increased GLUT1-IRS and mean count
      of Ki-67-positive cells were significantly associated with an increased grade of
      malignancy (p<0.0001), particularly in non-invasive tumours. GLUT1-IRS was
      significantly associated with a Ki-67-labelled proliferative fraction (p<0.0001).
      No significant association regarding tumour grade or stage was observed within
      the invasive carcinoma group. GLUT1 protein expression was found to be strongly
      correlated with increased malignant potential, particularly in non-invasive
      urothelial carcinomas. The increase of GLUT1 expression may reflect a preinvasive
      metabolic switch in terms of enhanced cell metabolism concomitant to known
      genetic alterations. A further increase in invasive carcinomas may be related to
      hypoxic conditions.

PMID- 22848281
TI  - IGF-IR in patients with advanced colorectal cancer in correlation with certain
      clinico-morphological factors: Initial report.
AB  - The insulin-like growth factor (IGF) system comprises two types of peptides (IGF
      I and IGF-II), two types of receptors (IGF-IR and IGF-IIR) and six IGF-binding
      proteins (BP). This system is mainly responsible for the growth and division of
      cells in the body, regulation of the cell cycle and prevention of apoptosis. The
      expression of IGF-IR was assessed in the cells of resected primary colorectal
      tumours in 88 patients (age, 36-87 years; mean 64.78; males, 48 and females, 40)
      treated surgically at the Second Department of General and Gastroenterological
      Surgery, Medical University of Bialystok, Poland, in relation to various clinico
      morphological factors. The post-operative material was analysed to find the
      histological type, location of lesions, lymph node involvement staging, distant
      metastases (pTNM classification), staging in Dukes' classification and the
      histopathological differentiation grade. The expression of IGF-IR in colorectal
      cancer cells was assessed using an immunohistochemical method. The findings were
      subjected to statistical analysis (Chi-square test, multivariation test and Mann
      Whitney U test). A positive IGF-IR expression (in at least 10% of cancer cells)
      was observed in 44 patients. The mean immunoreactive cell count for IGF-IR in all
      of the tumours studied was 30.79%. The current study showed no correlation of IGF
      IR expression in colorectal cancer cells with characteristics such as age and
      gender of patients, tumour location, type, histological differentiation or
      histopathological advancement. Immunohistological determination of IGF-IR
      expression in advanced colorectal cancer cells revealed controversial scores.
      Evaluation should be confirmed by using other methods and enhanced to include
      adenomas and early colorectal cancers.

PMID- 22848282
TI  - Effect of magnetic fluid hyperthermia on lung cancer nodules in a murine model.
AB  - The purpose of the present study was to investigate the therapeutic effect of
      magnetic fluid hyperthermia (MFH) induced by an alternating magnetic field (AMF)
      on human carcinoma A549 xenograft in nude mice. An animal model of human lung
      cancer was established by subcutaneous injection of human lung cancer A549 cells
      in BALB/c nude mice. The xenograft mice were randomly divided into four groups
      and each group was treated with an injection of a different concentration of
      magnetic fluid: control, low-dose (67.5 mg/ml), medium-dose (90.0 mg/ml) and high
      dose group (112.5 mg/ml), respectively. Following the injection (24 h), the tumor
      was heated in an AMF for 30 min. Tumor volumes were then measured every week. The
      therapeutic effect was assessed by measuring the tumor volume and weight.
      Pathological examination was performed with a light and electronic microscope
      following treatment. The temperature at the surface of the tumor in the low-,
      medium- and high-dose groups increased to 41.3, 44.5 and 46.8 degrees C,
      respectively. The tumor grew significantly slower in the medium- and high-dose
      groups (both p<0.05) compared to the control group. Cytoclasis and apoptosis were
      detected under light and electron microscopy. In conclusion, MFH induced by AMF
      inhibited tumor growth and promoted apoptosis of human carcinoma A549 cells in a
      xenograft mice model.

PMID- 22848283
TI  - Effect of temozolomide on the U-118 glioma cell line.
AB  - Glioblastomas (GBM) are the most lethal subtype of astrocytomas, with a mean
      patient survival rate of 12 months after diagnosis. The gold standard treatment
      of GBM, which includes surgery followed by the combination of radiotherapy and
      chemotherapy with temozolomide (TMZ), increases the survival rate to 14.6 months.
      The success of TMZ appears to be limited by the occurrence of chemoresistance
      that allows glioma cells to escape from death signaling pathways. However, the
      mechanism of TMZ action is yet to be clarified although some controversial
      results have been reported. Therefore, our aim was to evaluate the occurrence of
      apoptosis and autophagy in glioma cells treated with TMZ and to correlate TMZ
      action with the survival pathways Pi3K/Akt and ERK1/2 MAP kinase. Cell
      proliferation was evaluated by incorporation of bromodeoxyuridine. Apoptosis was
      studied by flow cytometry as well as by fluorescence confocal microscopy in order
      to evaluate the sub G0/G1 percentage of cells and chromatin condensation. The
      expression of the autophagy-associated protein, LC3, as well as Akt and ERK1/2
      was performed by Western blotting. In TMZ-treated GBM cells the expression of
      LC3, the autophagy-associated protein was increased and only a reduced percentage
      of cells underwent apoptosis. In addition, we showed that the phosphorylation
      status of Pi3K/Akt and ERK1/2 MAP kinase was maintained during the treatment with
      TMZ, suggesting that glioma cells escape from TMZ-induced cell death due to these
      signaling pathways. The chemoresistance of U-118 cells to TMZ was partially
      eradicated when cells were simultaneously treated with specific inhibitors of
      Pi3K/Akt and ERK1/2 MAP kinase signaling pathways and TMZ. Therefore, we
      hypothesized that in order to induce glioma cell death it is essential to
      evaluate the activation of the survival pathways and establish a combined therapy
      using TMZ and inhibitors of those signaling pathways.

PMID- 22848284
TI  - Expression of VEGF and MMP-9 and MRI imaging changes in cerebral glioma.
AB  - The purpose of the present study was to investigate the association of vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9)
      expression with the histopathological grading of tumors in cerebral glioma. A
      total of 45 patients with pathologically confirmed cerebral glioma were divided
      into two groups: a low-grade group (grades I and II, 21 cases) and a high-grade
      group (grades III and IV, 24 cases). Immunohistochemical staining of tumor
      samples showed the percentages of tumors expressing VEGF and MMP-9 in the high
      grade group to be 95.83 and 75%, respectively, significantly higher than those of
      the low-grade group (66.67 and 23.81%, P<0.05 and P<0.01, respectively). The
      magnetic resonance imaging (MRI) results indicated that the peripheral edema
      index (EI), enhancement percentage (EP), and the maximum diameter of the tumor in
      the high-grade group were significantly higher than those in the low-grade group
      (P<0.05, P<0.01, and P<0.05). Moreover, the expression of VEGF and MMP-9 was
      positively correlated with EI, EP and the maximum diameter of the tumor (P<0.05).
      Therefore, VEGF and MMP-9 expression were correlated to the invasion of glioma.
      The association of their expression levels with EI, EP and the maximum tumor
      diameter indicates that these markers may be used to estimate tumor malignancy
      for future clinical diagnosis and treatment.

PMID- 22848285
TI  - Overexpression of 14-3-3sigma counteracts tumorigenicity by positively regulating
      p73 in vivo.
AB  - 14-3-3sigma, one of the 14-3-3 family members, was initially identified as a
      human mammary epithelium-specific marker 1. The expression of 14-3-3sigma is
      directly regulated by p53. It has been demonstrated that 14-3-3sigma stabilizes
      p53 and enhances its transcriptional activity through the interaction with p53,
      suggesting that 14-3-3sigma has a positive feedback effect on p53. Our previous
      study showed that 14-3-3sigma is a direct transcriptional target of p73 and
      enhances the p73-mediated transcriptional as well as pro-apoptotic activity in
      vitro. In the present study, we explored the tumor-suppressive effect of 14-3
      3sigma by establishing a breast cancer xenograft nude mouse model with an
      inducible expression of 14-3-3sigma or with an inducible expression of p53/p73
      plus 14-3-3sigma with ADR treatment. Tumor formation was then assayed. Moreover,
      66 primary breast cancer specimens and paired tumor-free breast specimens
      obtained from the female patients were examined. Results showed that the
      expression of p73 and 14-3-3sigma in breast cancer specimens was significantly
      lower than the tumor-free breast specimens and that 14-3-3sigma expression was
      positively correlated with the expression of p73. Furthermore, overexpression of
      14-3-3sigma counteracts tumorigenicity by positively regulating p73 in p53
      mutated or -deficient cancers in vivo. Therefore, our results may lead to the use
      of 14-3-3sigma in the therapeutic application for the p53-mutated and p73
      expressed breast cancer patients.

PMID- 22848286
TI  - The prognostic importance of cathepsin D and E-cadherin in early breast cancer: A
      single-institution experience.
AB  - Molecular tools have increasingly been used for decision-making in patients with
      early breast cancer (EBC). Nevertheless, simple tools such as
      immunohistochemistry may still be required in particular cases to complement
      traditional and molecular prognosticators. In this study, the prognostic
      significance of three well-known immunohistochemical biomarkers, cathepsin D, E
      cadherin and Ki67, was studied in 270 patients with EBC, followed by a median
      time of 126 months in a single institution. Histological examination was
      performed to confirm the histopathological diagnosis and select specimens. The
      specimens were evaluated using immunohistochemistry and survival curves were
      plotted. Results revealed the following patient characteristics: node-negative/1
      3 lymph nodes in 228 (86%) patients, hormone receptor-positive in 217 (80%);
      triple-negative in 31 (11%), and Her2-overexpression in 23 (9%) patients. Breast
      cancer-related events occurred in 37 patients (14%). A total of 217 patients
      (80%) survived. Receiver operating characteristic analysis for breast cancer
      specific survival showed an area under curve for the clinicopathological model of
      0.75 (95% CI, 0.64-0.86), 0.79 (95% CI, 0.68-0.90) for the three-biomarker model,
      and 0.82 (95% CI, 0.72-0.92) for the E-cadherin and cathepsin D only model. We
      propose that a simple prognostic model based on combined scores of E-cadherin and
      cathepsin D may aid treatment decisions in patients with EBC.

PMID- 22848287
TI  - The prolyl isomerase Pin1 is overexpressed in human esophageal cancer.
AB  - Peptidyl-prolyl isomerase Pin1 specifically catalyzes the cis/trans-isomerization
      of proline in the target sequence of phosphorylated Ser/Thr-Pro in over 50
      critical regulatory proteins. Pin1 is abnormally overexpressed in a range of
      human cancers, including lung, breast, colon and prostate cancers. However, few
      reports of Pin1 overexpression are currently available in clinical samples.
      Therefore, we examined the expression of Pin1 and p53 in non-pathological human
      tissues and esophageal cancer tissues. In esophageal cancer tissues, Pin1 and p53
      immunoreactivity was detected in cancer cells in 67 and 58% of cases,
      respectively. Moreover, Pin1 and p53 immunoreactivity was significantly
      correlated with lymph node-positive disease and more advanced cancer stage. The
      results demonstrated that high expression levels of Pin1 correlated with high
      levels of p53. Therefore, Pin1 is suggested to play key roles in the regulation
      of esophageal cancer.

PMID- 22848288
TI  - Expression of stromal cell-derived factor-1alpha is an independent risk factor
      for lymph node metastasis in early gastric cancer.
AB  - Lymph node metastasis is considered to be a significant prognostic factor for
      early gastric cancer (EGC). However, no real consensus exists on which patient
      and/or tumor characteristics are associated with lymph node metastasis. We
      investigated whether stromal cell-derived factor (SDF)-1alpha expression
      correlates with lymph node metastasis in patients with EGC by
      immunohistochemically examining the expression of SDF-1alpha in 138 archival
      tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were
      grouped into SDF-1alpha-positive and SDF-1alpha-negative groups, respectively. No
      significant differences existed with respect to age, gender, tumor location,
      proportion of tumors >20 mm in size, macroscopic type, depth of invasion or
      histology between the SDF-1alpha-positive and -negative groups. However, the SDF
      1alpha-positive group was significantly correlated with lymphovascular invasion
      and lymph node metastasis. Results of the univariate analyses indicated that
      lymphovascular invasion, undifferentiated histology and SDF-1alpha positivity
      were statistically significant risk factors affecting lymph node metastasis in
      patients with EGC. Multivariate analyses showed that lymphovascular invasion
      [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009],
      undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF
      1alpha positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent
      risk factors predicting lymph node metastasis in EGC. In conclusion, these
      results suggest that SDF-1alpha expression in tumor cells is a predictive marker
      of lymph node metastasis in EGC.

PMID- 22848289
TI  - Impaired nuclear export of tumor-derived c-terminal truncated cyclin D1 mutant in
      ESCC cancer.
AB  - Cyclin D1 is a significant regulator of the G1- to S-phase transition and is
      often aberrant in human tumors of various origins. Although cancer-derived cyclin
      D1 mutants are potent oncogenes in vitro and in vivo, the mechanisms by which
      they contribute to neoplasia remaind to be elucidated. We previously identified a
      cyclin D1 mutation (Delta266-295) in esophageal cancer with deleted codons from
      266 to 295 of wild-type cyclin D1, the critical COOH-terminal regulatory
      sequences necessary for cyclin D1 nuclear export. In the present study, this
      cancer-derived cyclin D1-Delta266-295 was shown to be a constitutively nuclear
      cyclin D1 protein with a significantly increased oncogenic potential. Moreover,
      the cancer-derived cyclin D1-Delta266-295 mutant was found to retain its ability
      to bind to and activate CDK4, which in turn phosphorylates and inactivates the
      pRb protein and promotes cell cycle progression. In comparison to wild-type
      cyclin D1a, D1-Delta266-295 exhibited enforced nuclear accumulation. In addition,
      the transient transfection and ectopic expression of this nuclear localized D1
      Delta266-295 up-regulated endogenous Notch1 expression, indicating that the
      mutant retained its ability as a transcriptional regulator. Furthermore, data
      from the flow cytometry assay showed that D1-Delta266-295 fractionally increased
      >4N cell accumulation, and further analysis suggested the retriggering of DNA
      replication relevant to its inhibition of Cdt1 proteolysis. Therefore, the
      inappropriate nuclear localization of this cyclin D1 mutant may interfere with
      DNA replication in cultured cells, thereby contributing to genomic instability.

PMID- 22848290
TI  - Effects of TRPM8 on the proliferation and angiogenesis of prostate cancer PC-3
      cells in vivo.
AB  - Prostate cancer is a significant health concern. In the early stages, prostate
      cancer cells depend on androgens for growth and survival, hence androgen-ablation
      therapy at this time may be effective in causing tumor regression. However,
      treatment options for advanced hormone-refractory prostate cancers are still
      relatively inefficient. This study aimed to investigate the possible effects of
      TRPM8 on the proliferation and angiogenesis of androgen-independent cancer PC-3
      cells in vivo. Thirty male nude mice were divided into three groups: the PC-3, PC
      3-vector and PC-3-TRPM8 groups. PC-3, PC-3-vector and PC-3-TRPM8 cells were
      respectively inoculated in the right flank to establish a transplanted tumor
      model. The mice were treated daily for four weeks and each group was examined by
      histology and immunohistochemical staining for CD34, FAK and PCNA. A CD34 marked
      microvascular density (MVD) test was performed. Western blot analysis was used to
      detect the VEGF protein expression level. Compared to the PC-3 and PC-3-vector
      groups, the PC-3-TRPM8 group revealed a decrease in tumor volume (P=0.000 and
      P=0.000, respectively), MVD (P=0.045 and P=0.041, respectively), VEGF (P=0.000
      and P=0.000, respectively), FAK and PCNA. The correlation between MVD and VEGF
      was positive (r=0.419; P=0.021). These data show that the overexpression of TRPM8
      had a negative effect on the proliferation and angiogenesis progression of PC-3
      cells in vivo.

PMID- 22848292
TI  - Role of inflammation in oral carcinogenesis (Part I): Histological grading of
      malignancy using a binary system.
AB  - The aim of the present study was to assess the suppressant role of the
      inflammatory infiltrate in oral carcinogenesis through the immunohistochemical
      expression of CD8 and FOXP3 and to discuss how representative this expression
      proved, as well as other parameters considered to be of prognostic value. A total
      of 20 cases of oral epithelial dysplasia and 40 cases of oral squamous cell
      carcinoma were selected. The criteria suggested by the World Health Organization
      were used for the histological grading of dysplasia. For carcinoma, a binary
      method was developed for the present study using parameters such as type of
      invasion, maturity, presence of epithelial masses and dysmorphism of the masses.
      Immunohistochemical analysis was performed for assessment of the expression of
      anti-CD8 and anti-FOXP3 in cases of dysplasia and carcinoma. Although the
      inflammatory infiltrate was more intense in the majority of carcinomas, it
      exercised a protective role in the dysplasia cases, as CD8 expression was
      significantly greater. Although a correlation was found between CD8 and the
      intensity of the inflammatory infiltrate in the carcinoma cases, CD8 demonstrated
      >5% expression in only 32.5% of the cases, compared to 80% of the dysplasia
      cases. Thus, we suggest that the inflammatory infiltrate should not be used as a
      parameter in routine examinations, as it plays different roles in the various
      stages of carcinogenesis. The histological grading system for malignancy employed
      in the present study is indicated for the assessment of oral squamous cell
      carcinoma.

PMID- 22848291
TI  - Expression of PPARgamma and PTEN in human colorectal cancer: An
      immunohistochemical study using tissue microarray methodology.
AB  - Although aberrations of peroxisome proliferator-activated receptor gamma
      (PPARgamma) and phosphatase and tensin homolog (PTEN) expression have been
      identified in several other cancer types, certain previous studies have revealed
      that PPARgamma is abundant in normal and malignant tissue in the colon. The
      question of whether aberrant PTEN is involved in the initial stage or is a later
      event during colorectal carcinogenesis remains controversial. Relatively few
      studies have focused on the correlation of expression of PPARgamma and PTEN in
      various tissues. In the present study, paraffin-embedded blocks from 139 patients
      with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were
      selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130
      and 54 cores, respectively. Expression of PPARgamma and PTEN was examined using
      immunohistochemical staining on TMAs. There were no significant differences in
      the expression of PPARgamma (P=0.055) and PTEN (P=0.100) between the colorectal
      cancers, adenomas and paracancerous mucosas. However, correlations of PPARgamma
      expression with clinical stage (P=0.004) and PTEN expression with histological
      grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC
      specimens. Although the differences in PPARgamma and PTEN protein expression in
      human colorectal cancer may not be considered as early diagnostic markers, our
      results indicate that CRCs with a low expression or deletion of PTEN may progress
      towards invasion and even metastasis; thus, PTEN may have potential as a
      prognostic marker in human CRC.

PMID- 22848293
TI  - Mutations of the epidermal growth factor receptor gene in NSCLC patients.
AB  - Mutations of the epidermal growth factor receptor (EGFR) in patients with non
      small cell lung cancer (NSCLC) were identified by re-sequencing all exons of this
      gene to evaluate the frequencies of EGFR gene mutation and identify rare or novel
      EGFR mutations. A total of 55 NSCLC samples from 55 patients were included in the
      study. Genomic DNA was extracted and exons 1-28 of the EGFR gene were sequenced
      to identify mutations. The cDNA of the EGFR gene with P848L and T790M double
      mutants was constructed by introducing point mutations into the wild-type EGFR
      vector using a site-directed mutagenesis kit. Among the 55 patients with NSCLC, 8
      patients carried mutations of the EGFR gene. Notably, of the mutation-harboring
      patients with a pathological type of adenocarcinoma, 6 were non-smokers. The in
      vitro study demonstrated that the P848L mutant had a similar response to that of
      the wild-type EGFR after gefitinib treatment, and the P848L and T790M double
      mutant exhibited high resistance to gefitinib. These EGFR mutations
      preferentially occurred in lung adenocarcinoma patients, most of whom were non
      smokers. In the in vitro study, P848L mutant EGFR had a similar response as the
      wild-type EGFR to gefitinib treatment, suggesting that lung cancer patients with
      a rare mutation of EGFR, such as the P848L mutation, do not respond to gefitinib
      treatment.

PMID- 22848294
TI  - Long-term efficacy of oral alendronate therapy in an elderly patient with
      polyostotic fibrous dysplasia: A case report.
AB  - Polyostotic fibrous dysplasia (PFD) is a high- turnover bone disease that
      frequently entails chronic bone pain, pathological fractures and severe
      deformities. Recently, bisphosphonates have shown effective antiresorptive
      properties in the treatment of children or adults with PFD. We report on a 79
      year-old female with PFD, who had severe lower limb deformity and chronic bone
      pain in multiple sites of her extremities for more than 55 years. The patient
      experienced significant decrease in bone pain and bone turnover markers following
      long-term (8.5 years) treatment with a low-dose oral alendronate treatment (5
      mg/day). To the best of our knowledge, this is the first report of a long-term
      follow-up of a postmenopausal elderly patient with long-standing symptomatic PFD
      following continuous low-dose oral alendronate therapy. This case report
      indicates that long-term daily administration of low-dose alendronate alone is a
      potential treatment option for elderly patients with PFD, particularly those with
      long-standing bone pain.

PMID- 22848295
TI  - Consumption of vitamin B6 reduces colonic damage and protein expression of HSP70
      and HO-1, the anti-tumor targets, in rats exposed to 1,2-dimethylhydrazine.
AB  - Mounting evidence indicates that vitamin B6 is a protective factor for colon
      cancer. Elevations in colonic damage, cell proliferation and heat shock proteins
      (HSPs, molecular chaperones) have been suggested to be associated with colon
      carcinogenesis. This study was performed to examine the effect of dietary levels
      of vitamin B6 (1, 7 or 35 mg pyridoxine HCl/kg diet) for 22 weeks on colon
      damage, epithelial cell proliferation and expression of HSPs in rats exposed to
      1,2-dimethylhydrazine (DMH). Supplemental vitamin B6 with a low vitamin B6 diet
      (1 mg pyridoxine HCl/kg diet) significantly reduced fecal activity of intestinal
      alkaline phosphatase (an index of intestinal damage) and the colonic epithelium
      PCNA labeling index (a marker of cell proliferation). Analysis using ELISA
      indicated that supplemental vitamin B6 significantly lowered protein levels of
      colonic HSP70 and heme oxygenase-1, HSP32 (HO-1). However, real-time RT-PCR
      analysis revealed that the mRNA levels of these HSPs were not decreased by
      supplemental vitamin B6, suggesting that the lowering effect of vitamin B6 on the
      colon protein expression of the HSPs is mediated by mechanisms not involving
      altered gene expression. This study provided evidence that dietary supplemental
      vitamin B6 suppresses colon damage, epithelial cell proliferation and protein
      expression of HSP70 and HO-1, the targets for anti-tumor agents, in rats exposed
      to DMH.

PMID- 22848296
TI  - A possible predictive marker of progression for hepatocellular carcinoma.
AB  - The correlation between decreased levels of selenium and increased DNA damage and
      oxidative stress shows the significance of this trace element. A number of
      studies have provided evidence for lower serum, plasma and tissue levels of
      selenium in patients with various diseases and types of cancer. In this study,
      liver selenium concentrations were measured in tissue samples of patients with
      hepatocellular carcinoma (HCC) by atomic absorption spectrometry. The results
      showed that the selenium concentrations decreased when the malignant grade
      increased. Furthermore, a significant correlation was found between selenium
      levels and human selenium binding protein-1 (SELENBP1) down-regulation in the
      liver. Therefore, we suggest that the evaluation of selenium and SELENBP1
      concentrations can be used for improving the prognosis of HCC.

PMID- 22848297
TI  - A phase II study of mitomycin-C and S-1 as third-line chemotherapy in patients
      with advanced colorectal cancer.
AB  - This study was conducted to evaluate the efficacy and safety of the combination
      of mitomycin-C (MMC) and S-1 as third-line chemotherapy for patients with
      advanced colorectal cancer (CRC) showing resistance to irinotecan- and
      oxaliplatin-containing regimens. Patients were recruited into the study from
      January 2009 and 10 patients were enrolled for 10 months. However, since no
      patients had shown a response by 10 months, the study was terminated early
      according to the protocol. MMC 7 mg/m(2) was administered intravenously on day 1
      every 6 weeks in the first 4 cycles. S-1 was administered twice daily at 35
      mg/m(2), within 1 h of meals on days 1-14. Following a rest for 7 days, S-1 was
      administered again on days 22-35, followed by a 7-day rest. A total of 14 cycles
      were delivered for 10 patients. All 10 patients were assessable for response. A
      total of 3 patients (30%) had stable disease and the remaining 7 showed disease
      progression. With a median follow-up of 7 months, the median overall survival was
      10.5 months. Grade 3-4 myelotoxicities included neutropenia in two patients,
      anemia in two and thrombocytopenia in one. Grade 1-2 nausea and vomiting
      developed in 5 patients. One patient experienced grade 3 diarrhea. Grade 1-2 hand
      foot syndrome occurred in 4 patients. In conclusion, the combination of MMC and S
      1 as third-line chemotherapy in patients with advanced CRC appears to be well
      tolerated but has poor activity.

PMID- 22848298
TI  - hTERT methylation is necessary but not sufficient for telomerase activity in
      colorectal cells.
AB  - Colorectal cancers exhibit a high telomerase activity, usually correlated with
      the hypermethylation of the promoter of its hTERT catalytic subunit. Although
      telomerase is not expressed in normal tissue, certain proliferative somatic cells
      such as intestinal crypt cells have demonstrated telomerase activity. The aim of
      this study was to determine whether a correlation exists between telomerase
      activity, levels of hTERT methylation and telomere length in tumoral and normal
      colorectal tissues. Tumor, transitional and normal tissues were obtained from 11
      patients with a colorectal cancer. After bisulfite modification of genomic DNA,
      hTERT promoter methylation was analyzed by methylation-sensitive single-strand
      conformation analysis (MS-SSCA). Telomerase activity and telomere length were
      measured by a fluorescent-telomeric repeat amplification protocol assay and by
      Southern blotting, respectively. A significant increase of hTERT methylation and
      telomerase activity, and a reduction of the mean telomere length were observed in
      the tumor tissues compared to the transitional and normal mucosa. In the
      transitional and normal mucosa, telomerase activity was significantly lower than
      that in tumor tissues, even with high levels of hTERT methylation. Nevertheless,
      hTERT promoter methylation was not linearly correlated to telomerase activity.
      These data indicate that hTERT promoter methylation is a necessary event for
      hTERT expression, as is telomerase activity. However, methylation is not
      sufficient for hTERT activation, particularly in normal colorectal cells.

PMID- 22848299
TI  - Correlation of macrophage migration inhibitory factor gene polymorphism with the
      risk of early-stage cervical cancer and lymphatic metastasis.
AB  - Associations of functional single nucleotide polymorphisms in MIF-173G/C with
      early stage cervical cancer were investigated in a hospital-based case-control
      study on 250 patients with cervical cancer prior to surgery (including 49 cases
      with and 201 cases without lymphatic metastasis) and 147 healthy controls. The
      polymorphism was assessed using restriction fragment length polymorphism
      polymerase chain reaction, and the MIF serum concentration was examined using the
      enzyme-linked immunosorbent assay to analyze the correlation between the
      polymorphism and the MIF serum concentration. Carriers of the variant C allele in
      MIF-173 were at a significantly higher risk of cervical cancer compared to
      carriers of the wild-type allele (aOR=1.508; 95% CI, 1.128-2.016, p=0.05). The GC
      and CC genotypes may be the causative factors for cervical cancer (aOR=1.851; 95%
      CI, 1.132-3.027, p=0.013). Individuals with the GC+CC genotype and C allele at
      the MIF-173G/C site were at a significantly higher risk of cervical cancer and
      lymphatic metastasis. The risk of lymphatic metastasis in early stage cervical
      cancer was increased more than 1.6 times in patients with the CC and GC genotypes
      compared with those with the GG genotype. The genotype distribution and allele
      frequency of MIF-173G/C were statistically significant in the well-, moderately
      and poorly differentiated groups (P<0.05). Compared to the GG genotype and G
      allele, patients with GC and CC genotypes and C allele exhibited a lower degree
      of differentiation and a higher degree of malignancy. A significant difference
      was observed in MIF serum concentrations among the various subgroups (P<0.05).
      The early cervical cancer, lymphatic metastasis and poorly differentiated groups
      exhibited higher MIF levels in serum. Moreover, patients with the CC genotype
      exhibited higher MIF serum concentration, which could increase the risk of early
      stage cervical cancer and lymphatic metastasis. The results presented in this
      study provide the first evidence that the genetic polymorphism MIF-173 is
      associated with cervical cancer in humans. Detection of MIF serum concentration
      and genotyping may be used as biomarkers for early diagnosis and therapy for
      cervical cancer.

PMID- 22848300
TI  - Comparative expression of matrix metalloproteinases in low-grade mucoepidermoid
      carcinoma and typical lung cancer.
AB  - The molecular profile of low-grade mucoepidermoid carcinomas remains to be
      clarified. In the present study, matrix metalloproteinase (MMP) expression was
      compared in low-grade mucoepidermoid carcinoma (MEC) and typical lung cancer. The
      expression of MMP-2, MMP-7 and MMP-9 was detected by immunohistochemistry in a
      cohort of 110 patients (34 with low-grade MEC and 76 with matched typical lung
      cancers). A positive MMP-2 expression was found to be 35.29 vs. 65.79% in low
      grade MEC and typical NSCLCs (p=0.003); a positive MMP-7 expression was 41.18 vs.
      55.26% (p=0.172); and a positive MMP-9 expression was 35.29 vs. 57.89% (p=0.028).
      In conclusion, the expression of MMP-2 and MMP-9 in low-grade MEC is lower than
      that in typical lung carcinomas.

PMID- 22848301
TI  - Runx3 expression in lymph nodes with metastasis is associated with the outcome of
      gastric cancer patients.
AB  - Accumulating evidence shows that runt-related transcription factor 3 (Runx3) is a
      putative tumor suppressor in various types of cancer, the lower levels of which
      are associated with a less favorable cancer outcome. However, these studies were
      restricted to primary cancer lesions. Lymph node metastasis (LNM) is a
      significant factor in determining the prognosis of patients with gastric cancer
      and is a frequent target of chemotherapy. In the present study, we investigated
      the expression of Runx3 in the lymph nodes (LNs) of stomach carcinoma and the
      association of Runx3 expression with the prognosis of patients. The expression of
      Runx3 in LNs with and without metastasis was detected by reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blotting. The positive rate of
      Runx3 mRNA in LNM specimens was significantly lower (28.4%, 21 out of 74)
      compared to that of the non-metastatic samples (33.3%, 9 out of 27, P<0.05).
      Similar findings were obtained by Western blotting. Univariate analysis revealed
      that the loss of Runx3 expression in LNs was not only associated with poor
      clinicopathological factors, such as LNM, distant organ metastasis, later
      clinicopathological stages and deep infiltration, but also with a lower 5-year
      survival rate and poorer prognosis. These results strongly suggest a potential
      diagnostic value of Runx3 expression in LNs and multiple pathways contributing to
      the outcome of patients with gastric cancer.

PMID- 22848302
TI  - Estradiol induces JNK-dependent apoptosis in glioblastoma cells.
AB  - Estrogens exert multiple regulatory actions on cellular events in a variety of
      tissues including the brain. In the present study, the signaling mechanisms of
      the concentration-dependent effects of 17-beta-estradiol (estradiol) on
      glioblastoma cells were investigated. Cell viability was evaluated by the trypan
      blue exclusion assay. Cell growth and kinase activities were evaluated by
      immunocytochemistry and Western blotting. The results showed that high
      concentrations of estradiol inhibit growth and induce apoptosis in C6 rat glioma
      and T98G human glioblastoma cells. The blockade of the c-jun NH(2)-terminal
      kinase (JNK) signaling pathway prevented these effects of estradiol, indicating
      the critical role of the JNK/c-jun signaling cascade in glioblastoma cell growth
      inhibition and cell death in response to high concentrations of estradiol.
      Collectively, these findings highlight the potential of new discoveries in
      sensitizing estrogen-sensitive tumors to chemotherapeutic drugs, and may lead to
      the development of new JNK-based effective therapies.

PMID- 22848303
TI  - Novel BRCA1 deleterious mutation (c.1949_1950delTA) in a woman of Senegalese
      descent with triple-negative early-onset breast cancer.
AB  - Limited information exists regarding BRCA1 and BRCA2 genetic testing and genetic
      diversity in BRCA1 and BRCA2 in sub-Saharan African populations. We report a
      novel mutation that consists of a deletion of 2 bp (c.1949_1950delTA) in the exon
      11 of the BRCA1 gene. This is a frameshift mutation that causes the disruption of
      the translational reading frame resulting in a premature stop codon downstream in
      the BRCA1 protein. The mutation was present in a Senegalese woman with a triple
      negative breast tumor and a family history of breast cancer.

PMID- 22848304
TI  - HSulf-1 suppresses cell growth and down-regulates Hedgehog signaling in human
      gastric cancer cells.
AB  - Gastric cancer is the second most lethal cancer worldwide. Despite the current
      surgical and adjuvant therapies, 5-year survival remains less than 20-25% in the
      US, Europe and China. Therefore, there is an urgent need to identify new
      therapeutic targets for treating this malignant disease. Accumulating evidence
      has supported that aberrant activation of the Hedgehog signaling pathway plays a
      crucial role in tumorigenesis and progression of gastric cancer. Human sulfatase
      1 (HSulf-1) is a recently identified enzyme that desulfates cell surface heparan
      sulfate proteoglycans (HSPGs), which is critical for Hedgehog signal transduction
      under a highly sulfated state. HSulf-1 has recently emerged as a tumor suppressor
      gene in certain types of cancer, including ovarian, breast, myeloma and
      hepatocellular carcinoma; however, its role in gastric cancer remains to be
      elucidated. Therefore, we established HSulf-1-expressing monoclonal MKN28 gastric
      cancer cells to investigate its function in gastric cancer. Expression of HSulf-1
      significantly suppressed cellular proliferation and growth in MKN28 gastric
      cancer cells. Notably, HSulf-1 inhibits Gli-mediated transcription and down
      regulates the expression of Hedgehog target genes, including GLI1, PTCH1/2, HHIP,
      CCND1, C-MYC and BCL-2. Collectively, the study provides evidence that HSulf-1
      may function as a tumor suppressor in gastric cancer. It suppresses gastric
      cancer cell proliferation, possibly through abrogating the Hedgehog signaling
      pathway. The study provides new mechanistic insight into HSulf-1- mediated tumor
      suppression, and supports the use of HSulf-1 as a potential new therapeutic
      target in treating gastric cancer.

PMID- 22848305
TI  - Association of insulin-like growth factor-1 with thyroid nodules.
AB  - The aim of the present study was to investigate the relationship between insulin
      like growth factor-1 (IGF-1) and thyroid nodules. A total of 56 patients with
      thyroid nodules confirmed by physical examination and ultrasound screening were
      randomly selected. The patients were divided into three groups by radionuclide
      scan: the hot nodule group (group 1, n=18); the cold and solid nodule group
      (group 2, n=18); and the cold and cystic nodule group (group 3, n=20). Cystic
      fluid samples from patients with cystic cold thyroid nodules were defined as
      group 4. A control group of 18 healthy adults matched for age, gender and body
      mass index (group 0) was also included. For all participants, levels of the
      thyroid hormones, TT3, TT4, TSH and IGF-1, were determined by radioimmunoassay.
      The measurement data were expressed as the mean +/- standard deviation (SD). The
      analysis of variance was performed by the t-test and the correlation analysis was
      performed by linear regression. The serum levels of IGF-1 in the solid cold
      nodule group were significantly higher than those in the hot nodule group
      (P<0.05). Serum levels of IGF-1 in the cystic cold nodule group were
      significantly lower than those in the control group (P<0.05). The serum IGF-1
      levels in the cystic fluid were significantly lower than those in the cystic cold
      nodule (P<0.05) and the control groups (P<0.05). Additionally, the mean serum IGF
      1 level in patients with thyroid adenoma was significantly higher than that in
      the control group (P<0.05). The serum IGF-1 level may not be involved in the
      pathogenesis of hot thyroid nodules and cold and cystic thyroid nodules; however,
      it may play a significant role in the pathogenesis of certain solid cold thyroid
      nodules.

PMID- 22848307
TI  - Emetine regulates the alternative splicing of caspase 9 in tumor cells.
AB  - Exons 3 to 6 in the caspase 9 gene undergo alternative splicing in which the
      larger caspase 9 splice variant promotes apoptosis, in contrast to the dominant
      negative anti-apoptotic splice variant, the smaller caspase 9b. In this study,
      the regulation of the alternative splicing of caspase 9 pre-mRNA was examined in
      response to Emetine. Treatment of C33A cells, breast cancer MCF-7 cells and MCF
      7/Adr cells with Emetine dihydrochloride upregulated the level of smaller caspase
      9b mRNA and concomitantly decreased the mRNA level of larger caspase 9 in a dose-
      and time-dependent manner, indicating that Emetine desensitizes C33A, MCF-7 and
      MCF-7/Adr to cell death. In contrast, treatment of PC3 cells, a prostate cancer
      cell line, manifested an opposite effect: a greater production of the larger
      caspase 9 mRNA with a concomitant decrease of caspase 9b mRNA. Pretreatment with
      calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase
      2A (PP2A) blocked Emetine-induced alternative splicing in cells, in contrast to
      okadaic acid, a specific inhibitor of PP2A, demonstrating a PP1-mediated
      mechanism. These results suggest that the various splicing patterns of the
      caspase 9 gene that are regulated by chemotherapy reagents may contribute to the
      resistance or sensitization of the tumors to other cell death inducers.

PMID- 22848306
TI  - Oridonin-induced apoptosis in SW620 human colorectal adenocarcinoma cells.
AB  - Oridonin, a diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, inhibited
      the growth of human tumor cell lines SW620 (colon), MCF-7 (breast) and K562 (bone
      marrow), and induced significant levels of apoptosis in SW620. Morphological
      changes indicative of cell apoptosis were observed after the cells were exposed
      to oridonin for 24 h. Growth inhibition was associated with G1 phase arrest, and
      with time- and dose-dependent increases in caspase-3 activity. We therefore
      conclude that oridonin inhibits the proliferation of SW620 cells by induction of
      apoptosis via the activation of caspase-3. Our data suggest that oridonin may
      have significant potential as an anti-colorectal adenocarcinoma agent.

PMID- 22848308
TI  - Effects of S-1 as a second-line chemotherapy for patients with relapsed
      pancreatic cancer.
AB  - Adjuvant chemotherapy with gemcitabine is the standard treatment in Japan for
      patients who have undergone resection of pancreatic cancer. However, few reports
      have described suitable regimens for patients who present cancer relapse
      following adjuvant chemotherapy. In the present study, we retrospectively
      evaluated the efficacy and safety of S-1, an oral fluoropyrimidine derivative, as
      a second-line chemotherapy for patients who had suffered relapse of pancreatic
      cancer following adjuvant chemotherapy with gemcitabine. A total of 51 patients
      with pancreatic cancer suffered relapse after curative resection and subsequent
      adjuvant chemotherapy with gemcitabine at our institution. A group of 26 of these
      patients were administered S-1 orally twice daily after meals at a dose of 80
      mg/m(2) for body surface areas for 14 consecutive days, followed by a 7-day rest
      (S-1 group). The remaining 25 patients received no additional anticancer drugs
      other than continuation of gemcitabine (GEM/BSC group). During a median follow-up
      period of 35 months, a significant difference was observed in overall survival
      (OAS) between the S-1 group and the control group (median OAS, 20.9 vs. 13.7
      months; p=0.0157, log-rank test). Furthermore, there was a significant inter
      group difference in survival after relapse (SAR) (median SAR, 11.4 vs. 6.20
      months; p=0.0025, log-rank test). No increase in grade 3/4 hematological and non
      hematological toxicity was observed in the S-1 group. In conclusion, second-line
      chemotherapy using a combination of S-1 and adjuvant chemotherapy with
      gemcitabine may be an efficient and beneficial strategy for patients with
      relapsed pancreatic cancer.

PMID- 22848309
TI  - Expression of MMP-3 and TIMP-3 in gastric cancer tissue and its clinical
      significance.
AB  - The present study aimed to investigate the expression of matrix metalloproteinase
      3 (MMP-3) and the tissue inhibitor of metalloproteinase-3 (TIMP-3) in gastric
      cancer tissue, as well as to analyze the correlation between their expression and
      the occurrence of gastric cancer. Immunohistochemistry was used to determine the
      expression of MMP-3 and TIMP-3 in the gastric cancer tissue from 18 patients with
      early-stage gastric cancer (early-stage group) and 26 patients with advanced
      stage gastric cancer (advanced-stage group). Transmission electron microscopy
      (TEM) was used to observe the lymphocytes and tumor cells in gastric cancer
      tissue. The results showed that the expression of TIMP-3 was significantly
      higher, whereas that of MMP-3 and MMP-3/TIMP-3 was lower in gastric cancer tissue
      of the early-stage group than in that of the advanced-stage group (P<0.05). The
      TEM images revealed increased lymphocytes and inconspicuous tumor cells
      penetrating the basement membrane in gastric cancer tissue of the early-stage
      group, and decreased lymphocytes and obvious tumor cells penetrating the basement
      membrane in the advanced-stage group. In conclusion, MMP-3 and TIMP-3 may be used
      as indices for the invasion and metastasis of gastric cancer and possess marked
      clinical significance in the prognostic judgment of gastric cancer.

PMID- 22848310
TI  - The rare case of giant cell tumor occuring in the axial skeleton after 15 years
      of follow-up: Case report.
AB  - The majority of giant cell tumors (GCTs) occur in the ends of the long bones. The
      presence of more than one GCT in the axial skeleton is rare. A GCT is capable of
      remaining clinically latent following treatment and becoming active a number of
      years later. We report an extremely rare case of GCT occurring in the axial
      skeleton, involving the sacrum, thoracic spine and parieto-occipital skull in
      more than 15 years of follow-up.

PMID- 22848311
TI  - Different expression of alternative lengthening of telomere (ALT)-associated
      proteins/mRNAs in osteosarcoma cell lines.
AB  - Tumors, including osteosarcoma (OS), are capable of evading senescence and cell
      death, which is caused by telomere loss with cell division. Alternative
      lengthening of telomeres (ALT) is considered as the main telomere maintenance
      mechanism in OS. In this study, we investigated the expression of ALT-associated
      proteins and mRNAs in human OS cell lines. Western blotting was used to detect
      the protein expression in OS cell lines, while the expression of mRNA was
      determined by reverse-transcriptase PCR and quantitative real-time PCR analysis.
      Whole-genome expression arrays were used to analyze the expression of all the
      mRNAs involved in telomere maintenance mechanisms (TMMs) including human
      telomerase reverse transcriptase, promyelocytic leukemia proteins and other
      related proteins. OS and normal cell lines do not express telomerase reverse
      transcriptase (hTERT) as a key subunit of telomerase, although they show varying
      levels of ALT-associated proteins and mRNAs such as PML, Rad52, MRE11 and FEN1 by
      Western blotting and quantitative real-time PCR analysis. A number of mRNAs that
      play essential roles in ALT are expressed more in OS cell lines than in the
      osteoblast cell line, as shown by whole-genome expression arrays. In conclusion,
      OS cell lines maintain their telomere length primarily through the ALT mechanism.
      There are numerous other proteins that regulate this process in OS; therefore,
      anti-ALT therapy may be a more effective method to treat OS than anti-telomerase
      therapy.

PMID- 22848312
TI  - Rare case of dystrophia myotonica with mega cisterna magna.
AB  - Myotonic dystrophy is also known as dystrophia myotonica (DM). The condition is
      composed of at least two clinical disorders with overlapping phenotypes and
      distinct molecular genetic defects: myotonic dystrophy type 1, the classic
      disease originally described by Steinert, and myotonic dystrophy type 2, also
      called proximal myotonic myopathy (PROMM). Mega cisterna magna is thought to be
      an anatomic variant with no clinical significance. We report a rare case of type
      1 dystrophia myotonica in combination with mega cisterna magna.

PMID- 22848313
TI  - Self-medication patterns among medical students in South India.
AB  - BACKGROUND: Self-medication results in wastage of resources, increases resistance
      of pathogens and generally causes serious health hazards such as adverse drug
      reactions, prolonged suffering and drug dependence. This study was undertaken to
      determine the reasons for self-medication and the pattern of self-medication
      among medical students. METHOD: This cross-sectional descriptive study was
      conducted at the K.S. Hegde Medical Academy, Mangalore. The participants were
      medical students from first to final year. Medical students were selected through
      convenience sampling. The data was collected using a pre-tested semi-structured
      questionnaire. The data was analysed using SPSS version 16 and the results
      expressed as proportions. RESULTS: A total of 200 students, 121 (60.5%) female
      and 79 (39.5%) male, were included in the study. Of the medical students
      surveyed, self-medication was reported among 92%. The respondents who used self
      medication found it to be time- saving in providing relief from minor ailments.
      The most common ailments for which self-medication were used were: the common
      cold (69%), fever (63%) and headache (60%). The students consulted their
      textbooks (39%) and seniors or classmates (38%) for the medications. Antipyretics
      (71%), analgesics (65%), antihistamines (37%) and antibiotics (34%) were the most
      common self- medicated drugs. Of the respondents, 33% were unaware of the adverse
      effects of the medication and 5% had experienced adverse reactions. The majority
      (64%) of students advised medications to others, more often to family and
      friends. CONCLUSION: The prevalence of self-medication among medical students is
      high, facilitated by the easy availability of drugs and information from
      textbooks or seniors. A significant number of students are unaware of the adverse
      effects of the medication that they themselves take and suggest to others.
      Therefore, potential problems of self-medication should be emphasised to the
      students.

PMID- 22848314
TI  - The effect of smoking on the ocular surface and the precorneal tear film.
AB  - BACKGROUND: Smoking, both active and passive, creates a plethora of health
      related problems, which primarily affect the cardiovascular and respiratory
      systems. There is very little evidence on the effects of tobacco smoke on the
      eye, especially regarding anterior ocular surface related pathology. This study
      was undertaken to determine the effects of smoking on the ocular surface and the
      tear film in smokers. METHODS: A total of 51 (102 eyes) smokers and 50 (100 eyes)
      age-and gender-matched healthy non-smokers were included in this study. The
      ocular surface was evaluated by measuring tear film break-up time, surface
      staining with fluorescein, and corneal and conjunctival sensitivities, and by
      completing the Schirmer's II test. Data was analysed using Statistical Package
      for Social Sciences (SPSS) version 11.5. A p value less than 0.05 was considered
      statistically significant. RESULTS: The smoker group had significantly lower tear
      film break-up time, and corneal and conjunctival sensitivity than the nonsmoker
      group. Punctate staining was significantly higher in the smoker group than the
      non-smoker group. There was no statistically significant difference in Schirmer's
      II test results between the smoker and non-smoker group. CONCLUSION: Smoking
      caused adverse effects on the precorneal tear film and there was strong
      association between smoking and tear film instability. Although a causative
      relationship could not be determined, there is a need for further longitudinal
      studies.

PMID- 22848315
TI  - Flexible bronchoscopic removal of a three piece foreign body from a child's
      bronchus.
AB  - Foreign body aspiration can be a life-threatening event especially in young
      children because they have smaller diameters of airway lumen, moreover, the delay
      in the diagnosis and subsequent therapeutic intervention can further increase the
      risk of morbidity.(1, 2) A retained foreign body can result in inflammatory
      response and granulation tissue formation around the object which make the
      foreign body removal difficult.(3) In such situations surgical intervention is
      usually needed but with interventional pulmonology modalities we can restrict the
      need for surgery.(4) Rigid bronchoscopy under general anaesthesia is the gold
      standard of diagnosis and management of foreign body aspiration.(1) However,
      nowadays flexible bronchoscopy is more widely available and most pulmonary
      physicians are trained in its use so it can be used to remove such foreign
      bodies. We hereby report a case of a neglected foreign body which remained in the
      bronchus of a child for 11 days, successfully removed by flexible bronchoscopy.

PMID- 22848316
TI  - Is there a potential role for protein-conjugate pneumococcal vaccine in older
      adults?
AB  - Longstanding controversy over the efficacy of 23-valent pneumococcal
      polysaccharide vaccine (PPV23) led to a recommendation by the Joint Committee on
      Vaccination and Immunisation (JCVI) of the United Kingdom in March 2011, to
      discontinue routine use of PPV23 in older adults.(1) Following careful review of
      the evidence and feedback from stakeholders, the JCVI decided to retain the
      original policy of uniform vaccination of adults >65 years of age, while keeping
      the subject under continued review. In the United States, the Advisory Committee
      on Immunization Practices (ACIP) which is also concerned about the efficacy of
      PPV23 is currently considering a different strategy, i.e. adding 13-valent
      pneumococcal protein-conjugate vaccine (PCV13) for recommended use in adults,
      following recent Food and Drug Administration (FDA) approval for this purpose in
      adults over 50 years of age. It is therefore timely to review the options for
      prevention of pneumococcal disease in adults.

PMID- 22848317
TI  - Hamstrings tendon graft preparation for anterior cruciate ligament reconstruction
      using the WhipKnotTM soft tissue cinch technique.
AB  - BACKGROUND: Appropriate graft tension and secure graft incorporation in bone
      tunnels are essential for successful anterior cruciate ligament (ACL)
      reconstruction using hamstrings tendon autografts. The WhipKnotTM soft tissue
      cinch, introduced by Smith and Nephew in 2004, is an alternative option to the
      commonly used whipstitch technique during preparation of the hamstring autograft
      in ACL reconstruction. AIMS: To investigate the effectiveness of the WhipKnotTM
      soft tissue cinch and technique during the preparation of the tendon graft for
      ACL reconstruction. METHOD: A total of 33 ACL reconstruction operations performed
      between February 2011 and December 2011 were included in this study. These were
      performed by a single senior surgeon who used the WhipknotTM technique for the
      preparation of each graft. Four were used for each operation; two for each end of
      the harvested hamstrings tendons, including semitendinosus and gracilis tendons
      respectively. RESULTS: In total, 132 WhipKnots were used during the knee
      operations. Use of the WhipKnotTM technique resulted in successful graft
      preparations, tensioning and effective graft placement in the tibial and femoral
      tunnels in almost all instances. Only one case of WhipKnotTM failure (slippage)
      was recorded. CONCLUSION: These results indicate that the WhipknotTM technique is
      a safe, reliable and practical option for the preparation of the hamstrings
      autografts.

PMID- 22848318
TI  - Evaluation of free i-applications for tertiary level gross anatomy education.
AB  - BACKGROUND: The use of electronic resources in education, including i-
      applications used on portable handheld devices, is increasing. Apple(r) handheld
      devices are popular, with free applications the most prevalent download form.
      Many gross anatomy i- applications are available, however no information on the
      quality of free anatomy products is available. Rating such products could
      therefore guide product recommendations. AIM: To evaluate the quality and range
      of free iPod(r) applications that are applicable for tertiary level gross anatomy
      education. METHODS: A search of the iTunes(r) Application Store with keywords
      anatomy, free, medical, functional, clinical, gross, and human was performed,
      with inclusion based on free applications containing human gross anatomy usable
      for tertiary education purposes. Application specification was noted; each was
      trialled independently and rated for usability, specification, academic level,
      and quality (image and programme). RESULTS: Sixty-three applications were
      identified and eleven met inclusion criteria. Two provided gross anatomy of the
      entire body, nine examined specific regions or systems. Five were judged
      introductory in academic level, five intermediate, and one advanced. One
      application was rated low quality, and four excellent. None were considered
      difficult to use (six easy, five medium). Application size ranged between 1.2MB
      and 229MB (mean 27MB). CONCLUSIONS: There are few free i-applications for
      learning gross anatomy and most concentrate on individual body systems, with the
      academic level and usability of all products well rated. Results suggest some
      free I- applications could be suitable adjuncts for gross anatomy education at
      both an undergraduate and graduate level.

PMID- 22848319
TI  - Prevalence of depression in students of a medical college in New Delhi: A cross
      sectional study.
AB  - BACKGROUND: Medical education is associated with various pressures and stresses
      which can lead to depression. This study was undertaken to discover the
      prevalence of depression in medical students and various factors contributing to
      depression. METHOD: This is a cross-sectional, questionnaire-based study. Using
      stratified random sampling, 237 students were selected according to year of
      study. Patient Health Questionnaire (PHQ-9), based on PRIME-MD Today, was used to
      make a provisional diagnosis of depression. RESULTS: The overall prevalence of
      provisionally diagnosed depressive and major depressive disorder using PHQ-9 was
      21.5% and 7.6%, respectively. Year of study and academic performance of students
      had a statistically significant association with depression. Other factors,
      including gender, self-reported past history of depression, family history of
      psychiatric disorders, type of social support, family structure, number of
      siblings and education of parents were not found to have any significant
      association with prevalence of depression in the study. It was also observed that
      students were reluctant to seek help for depressive symptoms.

PMID- 22848320
TI  - Scale construction utilising the Rasch unidimensional measurement model: A
      measurement of adolescent attitudes towards abortion.
AB  - BACKGROUND: Measurement scales seeking to quantify latent traits like attitudes,
      are often developed using traditional psychometric approaches. Application of the
      Rasch unidimensional measurement model may complement or replace these
      techniques, as the model can be used to construct scales and check their
      psychometric properties. If data fit the model, then a scale with invariant
      measurement properties, including interval-level scores, will have been
      developed. AIMS: This paper highlights the unique properties of the Rasch model.
      Items developed to measure adolescent attitudes towards abortion are used to
      exemplify the process. METHOD: Ten attitude and intention items relating to
      abortion were answered by 406 adolescents aged 12 to 19 years, as part of the
      "Teen Relationships Study". The sampling framework captured a range of sexual and
      pregnancy experiences. Items were assessed for fit to the Rasch model including
      checks for Differential Item Functioning (DIF) by gender, sexual experience or
      pregnancy experience. RESULTS: Rasch analysis of the original dataset initially
      demonstrated that some items did not fit the model. Rescoring of one item (B5)
      and removal of another (L31) resulted in fit, as shown by a non-significant item
      trait interaction total chi-square and a mean log residual fit statistic for
      items of -0.05 (SD=1.43). No DIF existed for the revised scale. However, items
      did not distinguish as well amongst persons with the most intense attitudes as
      they did for other persons. A person separation index of 0.82 indicated good
      reliability. CONCLUSION: Application of the Rasch model produced a valid and
      reliable scale measuring adolescent attitudes towards abortion, with stable
      measurement properties. The Rasch process provided an extensive range of
      diagnostic information concerning item and person fit, enabling changes to be
      made to scale items. This example shows the value of the Rasch model in
      developing scales for both social science and health disciplines.

PMID- 22848321
TI  - Internet usage and openness to internet-delivered health information among
      Australian adults aged over 50 years.
AB  - BACKGROUND: The cost of healthcare in Australia's ageing population is ever
      increasing. In an attempt to reduce these rising costs, the internet has been
      suggested as a possible means of disseminating health-related information and
      promoting preventive health behaviours. OBJECTIVE: Our objective was to determine
      the proportion of Australians aged 50-74 years who have internet access, and the
      characteristics of internet usage, current online health information seeking
      behaviour, and the willingness to receive unsolicited health information via the
      Internet. METHOD: A random sample of N=25,511 urban older Australians aged 50 to
      74 years received a questionnaire via mail and were asked to complete questions
      concerning variables related to internet usage. N=8,762 returned a competed
      questionnaire. RESULTS: Eighty-two per cent of respondents reported having
      internet access, mainly at home (94%), and the majority actively use this
      technology (93%). Younger people and those of higher socio-economic status and
      higher education were more likely to have access (p<.001). Approximately 61%
      reported actively seeking health-related information online but only 32%
      expressed a willingness to receive unsolicited health information via the
      internet. Females were more likely to currently search for health-related
      information than males but were less likely to be open to receiving unsolicited
      health information (both p<.001). CONCLUSION: According to the data it appears
      the majority of urban Australians aged over 50 have access to the internet at
      some location and 60% of them use the internet for health-related purposes. The
      data also suggests, however, that delivering health information via the internet
      alone would disadvantage those who are older, less educated, and less financially
      well-off.

PMID- 22848322
TI  - Adverse drug reaction reporting in a pharmacovigilance centre of Nepal.
AB  - BACKGROUND: Pharmacovigilance is the "science and activities relating to the
      detection, assessment, understanding and prevention of adverse effects or any
      other drug related problems". Nepal joined the international pharmacovigilance
      programme as a full member in 2007. KIST Medical College, Lalitpur, Nepal joined
      the national programme as a regional centre from mid-July 2008. Currently, the
      pattern and scope of adverse drug reactions (ADRs) in Nepal remains unexplored.
      AIMS: To observe and analyse the pattern of ADRs at KIST Medical College,
      Lalitpur, Nepal. METHOD: A retrospective analysis of all ADRs reported to the
      centre from mid July 2008 to July 2011 was performed. Data was analysed for ADR
      severity, causality, and preventability. RESULTS: A total of 113 ADR reports were
      obtained from various clinical departments. The maximum number of reactions was
      due to antimicrobials, followed by anti-hypertensives and NSAIDs. CONCLUSION:
      Antimicrobials were the commonest group of drugs causing ADRs and the most
      commonly seen ADR was maculopapular rash followed by diarrhea and vomiting.

PMID- 22848323
TI  - Umbilical endometriosis mimicking as papilloma to general surgeons: A case
      report.
AB  - INTRODUCTION: Cutaneous or umbilical endometriosis is a rare entity that is often
      overlooked because of chronic abdominal pain. We present a case of umbilical
      hernia that presented to the general surgeons due to chronic abdominal pain and
      nodule in the umbilicus, which was clinically diagnosed as umbilical papilloma.
      CASE PRESENTATION: A 48-year old multiparous Caucasian woman presented with
      painful nodule in the umbilicus for two and half years. The nodule was excised
      and the histopathological diagnosis was umbilicus endometriosis. CONCLUSION:
      Umbilical endometriosis is a very rare disease but should be considered as a
      differential diagnosis in women presenting with umbilical swelling.

PMID- 22848325
TI  - Doctors - paradoxes and possibilities.

PMID- 22848324
TI  - Milk sharing and formula feeding: Infant feeding risks in comparative
      perspective?
AB  - The advent of Internet forums that facilitate peer-to-peer human milk sharing has
      resulted in health authorities stating that sharing human milk is dangerous.
      There are risks associated with all forms of infant feeding, including
      breastfeeding and the use of manufactured infant formulas. However, health
      authorities do not warn against using formula or breastfeeding; they provide
      guidance on how to manage risk. Cultural distaste for sharing human milk, not
      evidenced-based research, supports these official warnings. Regulating bodies
      should conduct research and disseminate information about how to mitigate
      possible risks of sharing human milk, rather than proscribe the practice
      outright.

PMID- 22848326
TI  - Schmidt's syndrome - Case report.
AB  - When immune dysfunction affects two or more endocrine glands and other non
      endocrine immune disorders are present, the polyglandular autoimmune (PGA)
      syndromes should be considered. The PGA syndromes are classified as two main
      types: PGA type I and PGA type II. We are reporting this case in which a patient
      had primary adrenal insufficiency, autoimmune hypothyroidism and insulin
      dependent diabetes mellitus and was diagnosed as "Schmidt's syndrome" (PGA type
      II). This syndrome is a very rare autoimmune disorder and difficult to diagnose
      because the symptoms of this syndrome depends on the gland which gets involved
      first. Our patient was treated and improved with corticosteroid, thyroxine and
      insulin therapy.

PMID- 22848327
TI  - Diabetic mastopathy.
AB  - Diabetic mastopathy is the occurrence of lymphocytic mastitis and stromal
      fibrosis in men as well as women having long-standing diabetes. Clinical and
      radiological appearance can raise a suspicion of malignancy and result in
      unnecessary biopsy. As these lesions are known to recur; failure to recognise
      them can have devastating results. A case of diabetic mastopathy is therefore
      presented for the knowledge and benefit of all so that unnecessary surgery can be
      avoided.

PMID- 22848328
TI  - Efficacy of fresh Aloe vera gel against multi-drug resistant bacteria in infected
      leg ulcers.
AB  - BACKGROUND: Infected leg ulcers are major health problems resulting in morbidity
      and disability and are usually chronic and refractory to antimicrobial treatment.
      AIMS: The present study is aimed at determining the bacteria involved in leg
      ulcers and their resistance patterns to commonly used antibiotics as well as to
      determine whether Aloe Vera has antibacterial activity against multi-drug
      resistant organisms and promotes wound healing. METHOD: A total of 30 cases with
      leg ulcers infected with multi-drug resistant organisms were treated with topical
      aloe vera gel and 30 age and sex-matched controls were treated with topical
      antibiotics. Culture and sensitivity was done from the wounds on alternate days
      and the ulcer was clinically and microbiologically assessed after 10 days. The
      results were compiled and statistically analysed. RESULTS: Cultures of the study
      group who were using aloe vera dressings showed no growth by the fifth day in 10
      (33.3%) cases, seventh day in another 16 (53.3%) and ninth day in two of the
      remaining four cases (6.7%) while in two (6.7%) cases there was no decrease in
      the bacterial count. This means that of the 30 cases, 28 showed no growth by the
      end of 11 days while two cases showed no decrease in bacterial count. Growth of
      bacteria in study group is decreased from 100% (30 cases) to 6.7% (2 cases) by
      day 11 with P<0.001. Cultures of the control group did not show any decrease in
      the bacterial growth by day 11. CONCLUSION: Aloe vera gel preparation is cheap
      and was effective even against multi-drug resistant organisms as compared to the
      routinely used topical anti-microbial agents.

PMID- 22848329
TI  - National programme on prevention and control of diabetes in India: Need to focus.

PMID- 22848330
TI  - The health of women treated for breast cancer: A challenge in primary care.
AB  - At least one in a hundred consultations in general practice in Australia involves
      women being treated for breast cancer. The challenges presented during these
      consultations test the quality of primary care. Firstly, women are reported to
      prefer to discuss their breast cancer-related problems with a specialist even
      though research suggests that patients generally prefer to consult with a general
      practitioner (GP). The extent to which these patients will have maintained or
      return to their previous level of functioning will be a reflection on the quality
      of primary care, as some breast cancer-related health issues may persist beyond
      the time period when they are undergoing specialist review. Further, psychosocial
      matters, sexuality and relationships may require repeated review and perhaps
      consultations involving family members and would therefore be better addressed by
      a GP. An increasingly urgent need exists to review how best to support people who
      are successfully treated for life limiting illnesses, such as breast cancer.

PMID- 22848331
TI  - Ileal volvulus and its association with carcinoid tumours.
AB  - Small bowel volvulus is a rare cause of bowel obstruction in the Western World.
      It is often divided into primary and secondary causes. This report presents a
      case of secondary ileal volvulus with underlying carcinoid tumour.

PMID- 22848332
TI  - The business of doctoring.

PMID- 22848333
TI  - Infertility: Why can't we classify this inability as disability?
AB  - Disability is a complex phenomenon. It reflects an interaction between features
      of a person's body and features of the society in which he or she lives.
      International Classification of Functioning, Disability and Health (ICF), lays
      stress on the functional as well as the structural problem of a person. All the
      definitions of disability also include the disorders of the reproductive and
      endocrine system. So infertility and impotency should also be included in the
      category of disability. It affects the participation in areas of life and can
      have a disabling affect on an individual. Like any other disability the couple
      has to adapt and integrate infertility in their sense of self thus infertility
      comes as a major life crisis. Medically, infertility, in most cases, is
      considered to be the result of a physical impairment or a genetic abnormality.
      Socially, couples are incapable of their reproductive or parental roles. On
      social level, infertility in most cultures remains associated with social stigma
      and taboo just like the social model of disability. Couples who are unable to
      reproduce may be looked down upon due to social stigmatisation. Infertility can
      lead to divorces and separation leading to a broken family life. Without
      labelling infertility as a disability, it is difficult for the people to access
      services and welfare benefits offered by the government. Infertility treatments
      are highly sophisticated so they are very expensive and are even not covered by
      insurance and government aid.In the light of all this it becomes imperative to
      categorise infertility as disability.

PMID- 22848334
TI  - Hybrid matrix grafts to favor tissue regeneration in rabbit femur bone lesions.
AB  - At present, typical approaches employed to repair fractures and other bone
      lesions tend to use matrix grafts to promote tissue regeneration. These grafts
      act as templates, which promote cellular adhesion, growth and proliferation,
      osteoconduction, and even osteoinduction, which commonly results in de novo
      osteogenesis. The present work aimed to study the bone-repairing ability of
      hybrid matrixes (HM) prepared with polyvinyl alcohol (PVA) and bioactive glass in
      an experimental rabbit model. The HM were prepared by combining 30% bioactive
      glass (nominal composition of 58% SiO2 -33 % CaO - 9% P2O5) and 70% PVA. New
      Zealand rabbits were randomly divided into the control group (C group) and two
      groups with bone lesions, in which one received a matrix implant HM (Implant
      group), while the other did not (no Implant group). Clinical monitoring showed no
      altered parameters from either the Implant or the no Implant groups as compared
      to the control group, for the variables of diet grades, day and night
      temperatures and hemograms. In the Implant group, radiologic and tomographic
      studies showed implanted areas with clean edges in femoral non-articular
      direction, and radio-dense images that suggest incipient integration. Minimum
      signs of phlogosis could be observed, whereas no signs of rejection at this
      imaging level could be identified. Histological analysis showed evidence of osteo
      integration, with the formation of a trabecular bone within the implant.
      Together, these results show that implants of hybrid matrixes of bioactive glass
      are capable of promoting bone regeneration.

PMID- 22848335
TI  - Practical Guidance on How to Handle Levodopa/Carbidopa Intestinal Gel Therapy of
      Advanced PD in a Movement Disorder Clinic.
AB  - Continuous dopaminergic delivery is recognized for the capacity to ameliorate
      symptoms in Parkinson's disease (PD). In advanced PD the short comings of orally
      administered Levodopa/Carbidopa include fluctuations resulting in unstable effect
      and dyskinesia. Levodopa/Carbidopa intestinal gel, LCIG, (Duodopa(r), Abbott
      Laboratories) is delivered continuously through a percutaneous endoscopic
      gastrostomy with the inner tube placed in the duodenum by means of a device (CADD
      legacy Duodopa pump (CE 0473)). The therapy implies continuous dopaminergic
      delivery directly to the duodenum and is therefore unaffected by gastric emptying
      and represents a major adjuvant in the treatment of advanced PD with significant
      improvement in motor and non-motor symptoms. The aim of this paper is to suggest
      the prerequisites for a LCIG clinic and propose a feasible set-up and lean
      organization of a movement disorder clinic. Secondly, the paper proposes
      practical handling of patients in LCIG treatment for advanced PD based on
      experience and initiation of LCIG treatment and follow-up in forty patients.

PMID- 22848336
TI  - Basic research on a cylindrical implant made of shape-memory alloy for the
      treatment of long bone fracture.
AB  - The internal fixing materials made from shape-memory alloys (SMAs) have recently
      been reported for long bone fracture. We present a new internal fixation
      technique using a cylindrical SMAs implant in a rat femoral fracture healing. The
      implant was designed in a shape to circumferentially fix the fractured bone using
      resilient SMA claws. To evaluate the fixing ability of the implant, three-point
      bending and rotation tests were performed. Fifteen female Wister rats were
      treated surgically as an experimental model. All rats were killed at 16 weeks
      postoperatively, and the radiological and histological evaluations were
      performed. In biomechanical test, the good fixation ability of the implant was
      demonstrated. In animal model, no cases of postoperative infection or death were
      encountered and postoperative gait was stable in all cases. Radiological
      examination at 16 weeks postoperatively demonstrated the implant firmly fixed to
      the fractured part, endosteal healing, and no callus formation in all cases. In
      Histological evaluation, bone union in all cases was characterized by
      endochondral ossification from within the medullary cavity. In conclusion, our
      cylindrical SMA implant provided good fixation in biomechanical tests, and
      achieved bone union in all 15 rats. If a larger size is designed in the future,
      our implant will be a clinically applicable, useful fixing material for fracture
      of the human long bones.

PMID- 22848337
TI  - Sonication of intramedullary nails: clinically-related infection and
      contamination.
AB  - BACKGROUND AND AIM: Sonication is currently considered the best procedure for
      microbiological diagnosis of implant-related osteoarticular infection, but
      studies in nail-related infections are lacking. The study aim was to evaluate
      implant sonication after intramedullary nail explantation, and relate it to
      microbiological cultures and clinical outcome. PATIENTS AND METHODS: A study was
      performed in two University Hospitals from the same city. Thirty-one patients
      with implanted nails were prospectively included, whether with clinical infection
      (8 cases) or without (23 cases). Retrieved nails underwent sonication according a
      previously published protocol. The clinical and microbiological outcome patient
      was related to the presence of microorganisms in the retrieved implant. RESULTS:
      Positive results appeared in 15/31 patients (9 with polymicrobial infections)
      almost doubling those clinically infected cases. The most commonly isolated
      organisms were Staphylococcus epidermidis (19.2 %) and Staphylococcus aureus
      (15.4 %). A significant relationship was found between the presence of positive
      cultures and previous local superficial infection (p=0.019). The presence of
      usual pathogens was significantly related to clinical infection (p=0.005) or
      local superficial infection (p=0.032). All patients with positive cultures showed
      pain diminution or absence of pain after nail removal (15/15), but this only
      occurred in 8 (out of 16) patients with negative cultures. CONCLUSIONS: In
      patients with previously diagnosed infection or local superficial infection,
      study of the hardware is mandatory. In cases where pain or patient discomfort is
      observed, nail sonication can help diagnose the implant colonization with
      potential pathogens that might require specific treatment to improve the final
      outcome.

PMID- 22848338
TI  - Digital Management of a Hysteroscopy Surgery Using Parts of the SNOMED Medical
      Model.
AB  - This work describes a hysteroscopy surgery management application that was
      designed based on the medical information standard SNOMED. We describe how the
      application fulfils the needs of this procedure and the way in which existing
      handwritten medical information is effectively transmitted to the application's
      database.

PMID- 22848339
TI  - Identification of miRNA signatures during the differentiation of hESCs into
      retinal pigment epithelial cells.
AB  - Retinal pigment epithelium (RPE) cells can be obtained through in vitro
      differentiation of both embryonic stem cells (ESCs) and induced pluripotent stem
      cells (iPSCs). We have previously identified 87 signature genes relevant to RPE
      cell differentiation and function through transcriptome analysis of both human
      ESC- and iPSC-derived RPE as well as normal fetal RPE. Here, we profile miRNA
      expression through small RNA-seq in human ESCs and their RPE derivatives. Much
      like conclusions drawn from our previous transcriptome analysis, we find that the
      overall miRNA landscape in RPE is distinct from ESCs and other differentiated
      somatic tissues. We also profile miRNA expression during intermediate stages of
      RPE differentiation and identified unique subsets of miRNAs that are gradually up
      or down-regulated, suggesting that dynamic regulation of these miRNAs is
      associated with the RPE differentiation process. Indeed, the down-regulation of a
      subset of miRNAs during RPE differentiation is associated with up-regulation of
      RPE-specific genes, such as RPE65, which is exclusively expressed in RPE. We
      conclude that miRNA signatures can be used to classify different degrees of in
      vitro differentiation of RPE from human pluripotent stem cells. We suggest that
      RPE-specific miRNAs likely contribute to the functional maturation of RPE in
      vitro, similar to the regulation of RPE-specific mRNA expression.

PMID- 22848340
TI  - A new mother-child play activity program to decrease parenting stress and improve
      child cognitive abilities: a cluster randomized controlled trial.
AB  - BACKGROUND: We propose a new play activity intervention program for mothers and
      children. Our interdisciplinary program integrates four fields of child-related
      sciences: neuroscience, preschool pedagogy, developmental psychology, and child
      and maternal psychiatry. To determine the effect of this intervention on child
      and mother psychosocial problems related to parenting stress and on the
      children's cognitive abilities, we performed a cluster randomized controlled
      trial. METHODOLOGY/PRINCIPAL FINDINGS: Participants were 238 pairs of mothers and
      typically developing preschool children (ages 4-6 years old) from Wakakusa
      kindergarten in Japan. The pairs were asked to play at home for about 10 min a
      day, 5 days a week for 3 months. Participants were randomly assigned to the
      intervention or control group by class unit. The Parenting Stress Index (PSI)
      (for mothers), the Goodenough Draw-a-Man intelligence test (DAM), and the new S-S
      intelligence test (NS-SIT) (for children) were administered prior to and 3 months
      after the intervention period. Pre-post changes in test scores were compared
      between the groups using a linear mixed-effects model analysis. The primary
      outcomes were the Total score on the child domain of the PSI (for child
      psychosocial problems related to parenting stress), Total score on the parent
      domain of the PSI (for maternal psychosocial problems related to parenting
      stress), and the score on the DAM (for child cognitive abilities). The results of
      the PSI suggested that the program may reduce parenting stress. The results of
      the cognitive tests suggested that the program may improve the children's fluid
      intelligence, working memory, and processing speed. CONCLUSIONS/SIGNIFICANCE: Our
      intervention program may ameliorate the children's psychosocial problems related
      to parenting stress and increase their cognitive abilities. TRIAL REGISTRATION:
      UMIN Clinical Trials Registry UMIN000002265.

PMID- 22848341
TI  - CXCL12/CXCR4 axis triggers the activation of EGF receptor and ERK signaling
      pathway in CsA-induced proliferation of human trophoblast cells.
AB  - INTRODUCTION: Our previous study has demonstrated Cyclosporin A (CsA) promotes
      the proliferation of human trophoblast cells. Therefore, we further investigate
      the intracellular signaling pathway involved in the CsA-induced proliferation of
      human trophoblast cells. METHODS: Enzyme-linked immunosorbent assay (ELISA) was
      performed to evaluate the regulation of CsA on CXCL12 secretion in human
      trophoblast cells. Immunofluorescence analysis and western blotting analysis were
      used to investigate the role of CXCL12/CXCR4 axis in the CsA-induced epidermal
      growth factor receptor (EGFR) phosphorylation in human trophoblast cells. 5-Bromo
      2'-deoxyuridine (BrdU) cell proliferation assay was performed to analyze the
      involvement of EGFR and its downstream extracellular signal-regulated protein
      kinase (ERK) signaling pathway in the CsA-induced proliferation of human
      trophoblast cells. RESULTS: Low concentration of CsA promoted the secretion of
      CXCL12, and recombinant human CXCL12 promoted the phosphorylation of EGFR in
      primary human trophoblast cells and choriocarcinoma cell line JEG-3. The
      inhibition of CXCL12 or CXCR4 by either neutralizing antibodies or small
      interfering RNA (siRNA) could completely block the CsA-induced EGFR
      phosphorylation. The CsA-induced proliferation of human trophoblast cells was
      effectively abrogated by the EGFR inhibitor AG1478 as well as the ERK inhibitor
      U0126, but not by the PI3K/PKB inhibitor LY294002. CsA promoted the activation of
      ERK in JEG-3 cells, which was markedly abrogated in the presence of CXCL12 siRNA,
      or CXCR4 siRNA, or AG1478. CONCLUSIONS: CsA may promote EGFR activation via
      CXCL12/CXCR4 axis, and EGFR downstream ERK signaling pathway may be involved in
      the CsA-induced proliferation of human trophoblast cells.

PMID- 22848342
TI  - Personal decision-making criteria related to seasonal and pandemic A(H1N1)
      influenza-vaccination acceptance among French healthcare workers.
AB  - BACKGROUND: Influenza-vaccination rates among healthcare workers (HCW) remain low
      worldwide, even during the 2009 A(H1N1) pandemic. In France, this vaccination is
      free but administered on a voluntary basis. We investigated the factors
      influencing HCW influenza vaccination. METHODS: In June-July 2010, HCW from wards
      of five French hospitals completed a cross-sectional survey. A multifaceted
      campaign aimed at improving vaccination coverage in this hospital group was
      conducted before and during the 2009 pandemic. Using an anonymous self
      administered questionnaire, we assessed the relationships between seasonal (SIV)
      and pandemic (PIV) influenza vaccinations, and sociodemographic and professional
      characteristics, previous and current vaccination statuses, and 33 statements
      investigating 10 sociocognitive domains. The sociocognitive domains describing
      HCWs' SIV and PIV profiles were analyzed using the classification-and-regression
      tree method. RESULTS: Of the HCWs responding to our survey, 1480 were paramedical
      and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21%
      and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations). Older
      age, prior SIV, working in emergency departments or intensive care units, being a
      medical HCW and the hospital they worked in were associated with both
      vaccinations; while work shift was associated only with PIV. Sociocognitive
      domains associated with both vaccinations were self-perception of benefits and
      health motivation for all HCW. For medical HCW, being a role model was an
      additional domain associated with SIV and PIV. CONCLUSIONS: Both vaccination
      rates remained low. Vaccination mainly depended on self-determined factors and
      for medical HCW, being a role model.

PMID- 22848343
TI  - Lipid content and composition during the oocyte development of two gorgonian
      coral species in relation to low temperature preservation.
AB  - Our previous studies have suggested that chilling sensitivity of coral oocytes
      may relate to their relatively high lipid intracellular content and lipid
      composition. The distribution of lipids during the oocyte development was
      determined here for the first time in two gorgonian species (Junceella juncea and
      Junceella fragilis). The main lipid classes in the two gorgonian oocytes were
      total lipid, wax ester, triacylglycerol, total fatty acid,
      phosphatidylethanolamine and phosphatidylcholine. The results indicated that
      early stage oocytes of J. juncea and J. fragilis were found to have increased
      lipid content than late stage oocytes. The content of wax ester was significantly
      higher in the early stage oocytes of two gorgonian corals (51.0+/-2.5 and 41.7+/
      2.9 ug/mm(3)/oocyte) than those of late stage oocytes (24.0+/-1.4 and 30.4+/-1.2
      ug/mm(3)/oocyte, respectively). A substantial amount of phosphatidylethanolamine
      and total fatty acid was detected at each stage of oocyte development in two
      gorgonian ranges from 107 to 42 ug/mm(3)/oocyte and 106 to 48 ug/mm(3)/oocyte,
      whilst low levels of phosphatidylcholine were found in two gorgonian oocytes. The
      levels of total lipid in the late stage oocytes of J. juncea were significantly
      higher than those of J. fragilis. The observed differences may partially be
      related to different habitat preferences as higher lipid levels in J. juncea, a
      deeper-water coral species exposed to lower temperature seawater, might relate to
      adjustments of cell membranes in order to increase membrane fluidity.

PMID- 22848345
TI  - Relative accuracy of cervical and anal cytology for detection of high grade
      lesions by colposcope guided biopsy: a cut-point meta-analytic comparison.
AB  - BACKGROUND: We recently reported, using a receiver operating characteristic area
      metric, the first meta-analytic comparison of the relative accuracy of cervical
      and anal cytology in detecting moderate or severe histopathologic lesions by
      magnification directed punch biopsy. The aim of the present research was to meta
      analytically examine cut-point specific operating characteristics (sensitivity,
      specificity) of cervical and anal cytology in detecting high grade squamous
      intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy.
      METHODOLOGY/PRINCIPAL FINDINGS: The primary eligibility requirement was
      availability of tabulated cytology (normal, atypical cells of unclear
      significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical
      squamous cells cannot rule out high grade [ASC-H]) and biopsy (<HSIL, >= HSIL)
      counts. Meta-analysis and meta-regression of diagnostic accuracy was performed
      with examination of study quality criteria and heterogeneity. Thirty-three
      cervical and 11 anal publications were eligible between 1990 and 2010. Meta
      analytically cut-point analysis showed that using a cut-point of ASCUS the
      sensitivity in both settings is similar while anal cytology is less specific than
      cervical cytology (specificity [95% confidence interval] 0.33 [0.20-0.49] vs.
      0.53[0.40-0.66], p = 0.04) for the detection of HSIL histopathology by colposcope
      directed punch biopsy. CONCLUSIONS/SIGNIFICANCE: Using a cytology cut-point of
      HSIL or ASC-H, anal cytology is less sensitive but comparably specific to
      cervical cytology. However, using a cut-point of ASCUS, differences in accuracy
      were of borderline significance.

PMID- 22848344
TI  - Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric
      autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.
AB  - Recent research in autism spectrum disorder (ASD) has aroused interest in
      anterior cingulate cortex and in the neurometabolite glutamate. We report two
      studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we
      acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS)
      in 8 children with ASD and 10 typically developing controls who were well matched
      for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we
      found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2%
      (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a
      larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched
      for age, gender, and IQ using proton magnetic resonance spectroscopic imaging
      ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition.
      Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr
      (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%,
      p<0.01) in the ASD sample were elevated above control. These two independent
      studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC
      in ASD, with possible right-lateralization. The hyperglutamatergic state may
      reflect an imbalance of excitation over inhibition in the brain as proposed in
      recent neurodevelopmental models of ASD.

PMID- 22848346
TI  - Microbial diversity of genital ulcer disease in men enrolled in a randomized
      trial of male circumcision in Kisumu, Kenya.
AB  - BACKGROUND: Medical male circumcision (MMC) reduces the risk of genital ulcer
      disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually
      transmissible agent was not identified in 50-60% of GUD specimens by polymerase
      chain reaction (PCR) assay. We sought to better define the etiology of GUD in men
      participating in the Kenyan trial and examine how MMC affects GUD etiology.
      METHODS: We defined GUD of unknown etiology as negative for HSV (type 1 and type
      2), T. pallidum, and H. ducreyi by PCR, and negative for HSV-2 and T. pallidum by
      serology. We identified bacterial microbiota in a subset of 59 GUD specimens
      using multitag pyrosequencing of the 16S rRNA gene, and compared results by
      unknown vs. STI-associated etiology. Statistical analysis employed Bray-Curtis
      similarity measure of bacterial community by etiology, hierarchical clustering
      and logistic regression. RESULTS: In 59 GUD specimens from 59 men, 23 (39%) had
      unknown etiology. Bacterial diversity was greater in GUD of unknown than STI
      etiology (p = 0.01). Fusobacteria (Fusobacterium spp. and Sneathia spp.) were
      more commonly detected in men with GUD of unknown etiology [adjusted OR = 5.67;
      95% CI: 1.63-19.8] as were Oxobacter spp. and Anaerovorax spp. [adjusted OR =
      3.12; 95% CI: 0.83-11.7]. Sequences from these four anaerobic bacterial taxa were
      more often detected in uncircumcised men than circumcised men (p<0.05).
      CONCLUSIONS: Anaerobic bacteria are more common in genital ulcers of
      uncircumcised men. The specific anaerobic bacteria associated with GUD of unknown
      etiology have cytotoxic properties that can exacerbate epithelial disruptions
      leading to ulcer-like appearance. MMC may reduce GUD through a reduction in these
      anaerobic bacteria.

PMID- 22848347
TI  - Social inequalities and mortality in Europe--results from a large multi-national
      cohort.
AB  - BACKGROUND: Socio-economic inequalities in mortality are observed at the country
      level in both North America and Europe. The purpose of this work is to
      investigate the contribution of specific risk factors to social inequalities in
      cause-specific mortality using a large multi-country cohort of Europeans.
      METHODS: A total of 3,456,689 person/years follow-up of the European Prospective
      Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of
      subjects coming from 9 European countries was recorded as proxy for socio
      economic status (SES). Cox proportional hazard model's with a step-wise inclusion
      of explanatory variables were used to explore the association between SES and
      mortality; a Relative Index of Inequality (RII) was calculated as measure of
      relative inequality. RESULTS: Total mortality among men with the highest
      education level is reduced by 43% compared to men with the lowest (HR 0.57, 95%
      C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk
      reduction was attenuated by 7% in men and 3% in women by the introduction of
      smoking and to a lesser extent (2% in men and 3% in women) by introducing body
      mass index and additional explanatory variables (alcohol consumption, leisure
      physical activity, fruit and vegetable intake) (3% in men and 5% in women).
      Social inequalities were highly statistically significant for all causes of death
      examined in men. In women, social inequalities were less strong, but
      statistically significant for all causes of death except for cancer-related
      mortality and injuries. DISCUSSION: In this European study, substantial social
      inequalities in mortality among European men and women which cannot be fully
      explained away by accounting for known common risk factors for chronic diseases
      are reported.

PMID- 22848349
TI  - Design and construction of "synthetic species".
AB  - Synthetic biology is an area of biological research that combines science and
      engineering. Here, I merge the principles of synthetic biology and regulatory
      evolution to create a new species with a minimal set of known elements. Using
      preexisting transgenes and recessive mutations of Drosophila melanogaster, a
      transgenic population arises with small eyes and a different venation pattern
      that fulfils the criteria of a new species according to Mayr's Biological Species
      Concept. The population described here is the first transgenic organism that
      cannot hybridize with the original wild type population but remains fertile when
      crossed with other identical transgenic animals. I therefore propose the term
      "synthetic species" to distinguish it from "natural species", not only because it
      has been created by genetic manipulation, but also because it may never be able
      to survive outside the laboratory environment. The use of genetic engineering to
      design artificial species barriers could help us understand natural speciation
      and may have practical applications. For instance, the transition from transgenic
      organisms towards synthetic species could constitute a safety mechanism to avoid
      the hybridization of genetically modified animals with wild type populations,
      preserving biodiversity.

PMID- 22848348
TI  - Epicutaneous exposure to staphylococcal superantigen enterotoxin B enhances
      allergic lung inflammation via an IL-17A dependent mechanism.
AB  - Atopic dermatitis (AD) is the initial step of the atopic march: the progression
      from AD to allergic rhinitis and asthma. There is a close association between
      skin barrier abnormalities and the development of AD and the atopic march. One of
      cardinal features of AD is that the lesional skin of the majority of AD patients
      is chronically colonized with Staphylococcus aureus with half isolates producing
      superantigen enterotoxin B (SEB). Although diverse roles of SEB in the
      pathogenesis and severity of AD have been recognized, whether SEB contributes to
      the dermal inflammation that drives lung inflammation and airway
      hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S.
      aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic
      march through an IL-17A dependent mechanism. When mice epicutaneously (EC)
      sensitized with allergen Ova, addition of topical SEB led to not only augmented
      systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune
      environment. The ability of SEB in enhancing Th17/IL-17 was mediated through
      stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6
      production. Epicutaneous sensitization of mice with a combination of Ova and SEB
      significantly enhanced Ova-induced AHR and granulocytic lung inflammation than
      Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on
      augmenting lung inflammation and AHR were markedly diminished. These findings
      suggest that chronic heavy colonization of enterotoxin producing S. aureus in the
      skin of patients with atopic dermatitis may have an important role in the
      development of atopic march via an IL-17A dependent mechanism.

PMID- 22848351
TI  - Reproductive characteristics of a Populus euphratica population and prospects for
      its restoration in China.
AB  - Populus euphratica is a dominant tree in riparian ecosystems in arid areas of
      northwest China, but it fails to regenerate in these systems. This study
      evaluates causes for the failure of sexual and asexual regeneration of this
      species in the wild. P. euphratica disperses as many as 85743 seeds/m(2) during
      summer, and the seeds germinate to 92.0% in distilled water and to 60.8% on silt.
      However, very few seeds (3.6%) can germinate on unflooded soil. The seed-rain
      season is prolonged by temporal variability in seed dispersal among individuals,
      which ensures that seedling emergence can occur during favorable conditions
      (i.e., floods and rainfall). As a result of water shortage and river channeling
      due to water usage and altered river flows, there are no safe sites on river
      banks for seed germination, which has led to the failure of P. euphratica to
      regenerate from seed. Root suckers of P. euphratica were present in 86% of the
      forest gaps investigated. However, extensive grazing has destroyed many of them
      and thus has reduced this form of regeneration. This research suggests that human
      activities are resulting in the failure of P. euphratica to regenerate. Changes
      in land management such as reduced use of concrete canals in Populus forests
      and/or reduced sheep grazing in these areas may promote their regeneration.

PMID- 22848350
TI  - Iodine-131 dose dependent gene expression in thyroid cancers and corresponding
      normal tissues following the Chernobyl accident.
AB  - The strong and consistent relationship between irradiation at a young age and
      subsequent thyroid cancer provides an excellent model for studying radiation
      carcinogenesis in humans. We thus evaluated differential gene expression in
      thyroid tissue in relation to iodine-131 (I-131) doses received from the
      Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed
      between 1998 and 2008 in the Ukrainian-American cohort with individual I-131
      thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and
      normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality
      control criteria. We first hybridized 32 randomly allocated RNA specimen pairs
      (T/N) on 64 whole genome microarrays (Agilent, 4*44 K). Associations of
      differential gene expression (log(2)(T/N)) with dose were assessed using Kruskall
      Wallis and trend tests in linear mixed regression models. While none of the genes
      withstood correction for the false discovery rate, we selected 75 genes with a
      priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the
      remaining 31 RNA specimen pairs (T/N). The qRT-PCR data were analyzed using
      linear mixed regression models that included radiation dose as a categorical or
      ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12,
      FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493) were confirmed to have a
      statistically significant differential dose-expression relationship. Our study is
      among the first to provide direct human data on long term differential gene
      expression in relation to individual I-131 doses and to identify a set of genes
      potentially important in radiation carcinogenesis.

PMID- 22848352
TI  - Investigating the global dispersal of chickens in prehistory using ancient
      mitochondrial DNA signatures.
AB  - Data from morphology, linguistics, history, and archaeology have all been used to
      trace the dispersal of chickens from Asian domestication centers to their current
      global distribution. Each provides a unique perspective which can aid in the
      reconstruction of prehistory. This study expands on previous investigations by
      adding a temporal component from ancient DNA and, in some cases, direct dating of
      bones of individual chickens from a variety of sites in Europe, the Pacific, and
      the Americas. The results from the ancient DNA analyses of forty-eight
      archaeologically derived chicken bones provide support for archaeological
      hypotheses about the prehistoric human transport of chickens. Haplogroup E mtDNA
      signatures have been amplified from directly dated samples originating in Europe
      at 1000 B.P. and in the Pacific at 3000 B.P. indicating multiple prehistoric
      dispersals from a single Asian centre. These two dispersal pathways converged in
      the Americas where chickens were introduced both by Polynesians and later by
      Europeans. The results of this study also highlight the inappropriate application
      of the small stretch of D-loop, traditionally amplified for use in phylogenetic
      studies, to understanding discrete episodes of chicken translocation in the past.
      The results of this study lead to the proposal of four hypotheses which will
      require further scrutiny and rigorous future testing.

PMID- 22848353
TI  - Analysis of domain-swapped oligomers reveals local sequence preferences and
      structural imprints at the linker regions and swapped interfaces.
AB  - BACKGROUND: 3D domain swapping is an oligomerization process in which structural
      elements get exchanged between subunits. This mechanism grasped interest of many
      researchers due to its association with neurodegenerative diseases like
      Alzheimer's disease, spongiform encephalopathy etc. Despite the biomedical
      relevance, very little is known about understanding this mechanism. The quest for
      ruling principles behind this curious phenomenon that could enable early
      prediction provided an impetus for our bioinformatics studies. METHODOLOGY: A
      novel method, HIDE, has been developed to find non-domain-swapped homologues and
      to identify hinge from domain-swapped oligomers. Non-domain-swapped homologues
      were identified from the protein structural databank for majority of the domain
      swapped entries and hinge boundaries could be recognised automatically by means
      of successive superposition techniques. Different sequence and structural
      features in domain-swapped proteins and related proteins have also been analysed.
      CONCLUSIONS: The HIDE algorithm was able to identify hinge region in 83% cases.
      Sequence and structural analyses of hinge and interfaces reveal amino acid
      preferences and specific conformations of residues at hinge regions, while
      comparing the domain-swapped and non-domain-swapped states. Interactions differ
      significantly between regular dimeric interfaces and interface formed at the site
      of domain-swapped examples. Such preferences of residues, conformations and
      interactions could be of predictive value.

PMID- 22848354
TI  - Tobacco use or body mass--do they predict tuberculosis mortality in Mumbai,
      India? Results from a population-based cohort study.
AB  - Tobacco use and under-nutrition are major public health concerns and tuberculosis
      is a major cause of morbidity and mortality in India. Using a cohort of 148,173
      persons (recruited 1991-1997 and followed-up 1997-2003) the joint effects of
      tobacco use and BMI on tuberculosis mortality was studied. Tobacco use in any
      form and low-BMI had joint effect on tuberculosis mortality and the interaction
      effect was synergistic in men and antagonistic in women. Self-reported
      tuberculosis was associated with increased risk of tuberculosis mortality. In
      contrast, no such association was observed for self-reported diabetes persons.
      The risk pattern remained unchanged even after excluding tuberculosis deaths
      occurred within 1(st) two years of follow-up. This study highlights importance of
      age consideration of individual while excluding early deaths. Around 27% male
      tuberculosis deaths were attributable to their being underweight and smoker,
      while 22% male and 37% female deaths were attributable to their being underweight
      and smokeless tobacco user.

PMID- 22848355
TI  - Evolution of heterogeneity (I2) estimates and their 95% confidence intervals in
      large meta-analyses.
AB  - BACKGROUND: Assessment of heterogeneity is essential in systematic reviews and
      meta-analyses of clinical trials. The most commonly used heterogeneity measure,
      I(2), provides an estimate of the proportion of variability in a meta-analysis
      that is explained by differences between the included trials rather than by
      sampling error. Recent studies have raised concerns about the reliability of I(2)
      estimates, due to their dependence on the precision of included trials and time
      dependent biases. Authors have also advocated use of 95% confidence intervals
      (CIs) to express the uncertainty associated with I(2) estimates. However, no
      previous studies have explored how many trials and events are required to ensure
      stable and reliable I(2) estimates, or how 95% CIs perform as evidence
      accumulates. METHODOLOGY/PRINCIPAL FINDINGS: To assess the stability and
      reliability of I(2) estimates and their 95% CIs, in relation to the cumulative
      number of trials and events in meta-analysis, we looked at 16 large Cochrane meta
      analyses--each including a sufficient number of trials and events to reliably
      estimate I(2)--and monitored the I(2) estimates and their 95% CIs for each year
      of publication. In 10 of the 16 meta-analyses, the I(2) estimates fluctuated more
      than 40% over time. The median number of events and trials required before the
      cumulative I(2) estimates stayed within +/-20% of the final I(2) estimate was 467
      and 11. No major fluctuations were observed after 500 events and 14 trials. The
      95% confidence intervals provided good coverage over time.
      CONCLUSIONS/SIGNIFICANCE: I(2) estimates need to be interpreted with caution when
      the meta-analysis only includes a limited number of events or trials. Confidence
      intervals for I(2) estimates provide good coverage as evidence accumulates, and
      are thus valuable for reflecting the uncertainty associated with estimating I(2).

PMID- 22848357
TI  - Comparing trawl and creel fishing for Norway lobster (Nephrops norvegicus):
      biological and economic considerations.
AB  - This study compares the fishing activity and landings of the trawl and creel
      fisheries for Norway lobster (Nephrops norvegicus (L.)) off the Portuguese coast,
      and evaluates the financial viability of two vessels typical of each fleet.
      Crustacean trawlers are part of an industrial fleet that, besides Nephrops,
      targets deep water shrimps. Creels are used by a multi-gear, multi-target
      artisanal fleet, fishing only in areas unavailable to trawlers and, when catching
      Nephrops, set specifically to target this species. Trawlers have in recent years
      contributed with 85% of the landings in weight, but only 74% in value (2005-2009
      average). Despite smaller landings, the Nephrops creel fishery provides
      individuals of larger size and in better condition, thereby obtaining higher unit
      prices. Economic viability was also higher for the creel vessel, with trawling
      being only viable if major costs (such as labor and fuel) are covered by the
      revenue from other target species (e.g., the rose shrimp). At present, Nephrops
      populations on the South and SW coast are subject to intense fishing and to a
      recovery plan. The possibility of reallocation of some of the fishing effort
      directed at Nephrops from trawlers to creels is discussed in terms of the
      conservation of the resource and economic return.

PMID- 22848356
TI  - Interleukin-10 haplotype may predict survival and relapse in resected non-small
      cell lung cancer.
AB  - IL-10 is associated with tumor malignancy via immune escape. We hypothesized that
      IL-10 haplotypes categorized by IL-10 promoter polymorphisms at -1082A>G, 
      819C>T, and -592C>A might influence IL-10 expression and give rise to non-small
      cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected
      adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by
      direct sequencing and polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10
      mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on
      overall survival (OS) and relapse free survival (RFS) were determined by Kaplan
      Meier and multivariate Cox regression analysis. The results showed that IL-10
      mRNA levels were significantly higher in tumors with the non-ATA haplotype than
      with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had
      shorter OS and RFS periods than did patients with the ATA haplotype. This may be
      associated with the observation that the number of tumor-infiltrating lymphocytes
      was decreased in the tumors with higher levels of IL-10. Consistently, T cells
      from the peripheral blood of the patients with non-ATA haplotype were more
      susceptible to apoptosis and less cytotoxic to tumor cells, compared to those
      from the patients with ATA haplotype. The results suggest that IL-10 can promote
      tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL
      10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict
      survival and relapse in resected NSCLC, helping clinicians to make appropriate
      decisions on treatment of the patients.

PMID- 22848358
TI  - Hypercholesterolemia is associated with the apolipoprotein C-III (APOC3) genotype
      in children receiving HAART: an eight-year retrospective study.
AB  - Polymorphisms in apolipoprotein genes have shown to be predictors of plasma lipid
      levels in adult cohorts receiving highly active antiretroviral therapy (HAART).
      Our objective was to confirm the association between the APOC3 genotype and
      plasma lipid levels in an HIV-1-infected pediatric cohort exposed to HAART. A
      total of 130 HIV-1-infected children/adolescents that attended a reference center
      in Argentina were selected for an 8-year longitudinal study with retrospective
      data collection. Longitudinal measurements of plasma triglycerides, total
      cholesterol, HDL-C and LDL-C were analyzed under linear or generalized linear
      mixed models. The contribution of the APOC3 genotype at sites -482, -455 and 3238
      to plasma lipid levels prediction was tested after adjusting for potential
      confounders. Four major APOC3 haplotypes were observed for sites -482/-455/3238,
      with estimated frequencies of 0.60 (C/T/C), 0.14 (T/C/C), 0.11 (C/C/C), and 0.11
      (T/C/G). The APOC3 genotype showed a significant effect only for the prediction
      of total cholesterol levels (p<0.0001). However, the magnitude of the differences
      observed was dependent on the drug combination (p = 0.0007) and the drug exposure
      duration at the time of the plasma lipid measurement (p = 0.0002). A lower risk
      of hypercholesterolemia was predicted for double and triple heterozygous
      individuals, mainly at the first few months after the initiation of Ritonavir
      boosted protease inhibitor-based regimens. We report for the first time a
      significant contribution of the genotype to total cholesterol levels in a
      pediatric cohort under HAART. The genetic determination of APOC3 might have an
      impact on a large portion of HIV-1-infected children at the time of choosing the
      treatment regimens or on the counter-measures against the adverse effects of
      drugs.

PMID- 22848359
TI  - Detection of metabolic fluxes of O and H atoms into intracellular water in
      mammalian cells.
AB  - Metabolic processes result in the release and exchange of H and O atoms from
      organic material as well as some inorganic salts and gases. These fluxes of H and
      O atoms into intracellular water result in an isotopic gradient that can be
      measured experimentally. Using isotope ratio mass spectroscopy, we revealed that
      slightly over 50% of the H and O atoms in the intracellular water of
      exponentially-growing cultured Rat-1 fibroblasts were isotopically distinct from
      growth medium water. We then employed infrared spectromicroscopy to detect in
      real time the flux of H atoms in these same cells. Importantly, both of these
      techniques indicate that the H and O fluxes are dependent on metabolic processes;
      cells that are in lag phase or are quiescent exhibit a much smaller flux. In
      addition, water extracted from the muscle tissue of rats contained a population
      of H and O atoms that were isotopically distinct from body water, consistent with
      the results obtained using the cultured Rat-1 fibroblasts. Together these data
      demonstrate that metabolic processes produce fluxes of H and O atoms into
      intracellular water, and that these fluxes can be detected and measured in both
      cultured mammalian cells and in mammalian tissue.

PMID- 22848360
TI  - Application of the community oral health indicator by non-dental personnel and
      its contribution to oral healthcare.
AB  - OBJECTIVE: To validate the Community Oral Health Indicator-COHI by non-dental
      personnel. METHODS: Risk assessment is an essential component in the decision
      making process. Therefore, the COHI, an instrument to evaluate population oral
      health situation in a simple manner, was created. Community Health Agents (CHA)
      were trained to use the COHI (variables as number of teeth, presence of cavities,
      residual dental roots, oral lesions, etc.), while dentists for the COHI and DMFT.
      60 individuals were examined, by CHA and DS, with these indicators in order to
      validate the use of COHI by non-dental personnel. RESULTS: Dental and soft
      tissues problems were well spread among those individuals. People with and
      without soft tissue damage, as well as with and without use and/or need for
      prostheses were found in the sample, proving it to be a heterogeneous population
      for the evaluated factors and representing the real population. The results of
      examinations performed by dentists using the COHI and DMF-T/dmf-t presented
      strong agreement when comparing the two instruments. When COHI and DMFT were
      compared, the results showed a concordance of 0.86 for the number of present
      teeth, and 0.85 for the number of residual roots. Likewise, when analyzing the
      data comparing the use of the COHI by DS and CHA a high agreement level,
      specificity and sensitivity was found. CONCLUSION: The COHI has shown to be
      useful for detecting problems in oral health. Therefore, COHI may be used, after
      training, by non-dental personnel, contributing to the planning and organization
      of the community dental assistance.

PMID- 22848361
TI  - Water-pipe smoking and metabolic syndrome: a population-based study.
AB  - Water-pipe (WP) smoking has significantly increased in the last decade worldwide.
      Compelling evidence suggests that the toxicants in WP smoke are similar to that
      of cigarette smoke. The WP smoking in a single session could have acute harmful
      health effects even worse than cigarette smoking. However, there is no evidence
      as such on long term WP smoking and its impact on chronic health conditions
      particularly cardiovascular and metabolic conditions. Therefore, we conducted
      this study to investigate the relationship between WP smoking and metabolic
      syndrome (MetS). This was a cross-sectional study carried out in Punjab province
      of Pakistan using the baseline data of a population-based study--Urban Rural
      Chronic Diseases Study (URCDS). Information was collected by trained nurses
      regarding the socio-demographic profile, lifestyle factors including WP smoking,
      current and past illnesses. A blood sample was obtained for measurement of
      complete blood count, lipid profile and fasting glucose level. MetS was
      ascertained by using the International Diabetic Federation's criteria. We carried
      out multiple logistic regressions to investigate the association between WP
      smoking and MetS. Final sample included 2,032 individuals--of those 325 (16.0%)
      were current WP smokers. Age adjusted-prevalence of MetS was significantly higher
      among current WP smokers (33.1%) compared with non-smokers (14.8%). Water-pipe
      smokers were three times more likely to have MetS (OR 3.21, 95% CI 2.38-4.33)
      compared with non-smokers after adjustment for age, sex and social class. WP
      smokers were significantly more likely to have hypertriglyceridemia (OR 1.63, 95%
      CI 1.25-2.10), hyperglycaemia (OR 1.82, 95% CI 1.37-2.41), Hypertension (OR 1.95,
      95% CI 1.51-2.51) and abdominal obesity (OR 1.93, 95% CI 1.52-2.45). However,
      there were no significant differences in HDL level between WP smokers and non
      smokers. This study suggests that WP smoking has a significant positive (harmful)
      relationship with MetS and its components.

PMID- 22848362
TI  - Weight cycling enhances adipose tissue inflammatory responses in male mice.
AB  - BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed
      to dysregulated production, release of cytokines and adipokines and to
      dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional
      interventions such as dieting are often accompanied by repeated bouts of weight
      loss and regain, a phenomenon known as weight cycling (WC). METHODS: In this work
      we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate
      metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two
      or three consecutive times by alternation of a high-fat (HF) diet with standard
      chow (SC). RESULTS: The body mass (BM) grew up in each cycle of HF feeding, and
      decreased after each cycle of SC feeding. The alterations observed in the animals
      feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum
      and adipose tissue expression of adipokines were not recuperated after WC.
      Moreover, the longer the HF feeding was (two, four and six months), more severe
      the adiposity was. After three consecutive WC, less marked was the BM reduction
      during SC feeding, while more severe was the BM increase during HF feeding.
      CONCLUSION: In conclusion, the results of the present study showed that both the
      HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with
      repercussion in blood lipids, homeostasis of glucose-insulin and adipokine
      levels. The simple reduction of the BM during a WC is not able to recover the
      high levels of adipokines in the serum and adipose tissue as well as the pro
      inflammatory cytokines enhanced during a cycle of HF diet. These findings are
      significant because a milieu with altered adipokines in association with WC
      potentially aggravates the chronic inflammation attributed to dysregulated
      production and release of adipokines in mice.

PMID- 22848363
TI  - Genomic characterization of a novel virus of the family Tymoviridae isolated from
      mosquitoes.
AB  - BACKGROUND: The family Tymoviridae comprises three plant virus genera, including
      Tymovirus, Marafivirus, and Maculavirus, which are found in most parts of the
      world and cause severe agricultural losses. We describe a putatively novel member
      of the family Tymoviridae, which is isolated from mosquitoes (Culex spp.),
      referred to as CuTLV. METHODS AND RESULTS: The CuTLV was isolated by cell
      culture, which replicates and causes cytopathic effects in Aedes albopictus C6/36
      cells, but not in mammalian BHK-21 or Vero cells. The complete 6471 nucleotide
      sequence of CuTLV was determined. The genome of CuTLV is predicted to contain
      three open reading frames (ORFs). The largest ORF1 is 5307 nucleotides (nt) in
      length and encodes a putative polypeptide of 1769 amino acids (aa), which
      contains the conserved motifs for the methyltransferase (MTR), Tymovirus
      endopeptidase (PRO), helicase (HEL), and RNA-dependent RNA polymerase (RdRp) of
      the replication-associated proteins (RPs) of positive-stranded RNA viruses. In
      contrast, the ORF1 sequence does not contain the so-called "tymobox" or
      "marafibox", the conserved subgenomic RNA promoter present in all tymoviruses or
      marafiviruses, respectively. ORF2 and ORF3 putatively encode a 248-aa coat
      protein (CP) and a proline-rich 149-aa polypeptide. The whole genomic nucleotide
      identity of CuTLV with other members of family Tymoviridae ranged from 46.2%
      (ChiYMV) to 52.4% (GFkV). Phylogenetic analysis based on the putative RP and CP
      genes of CuTLV demonstrated that the virus is most closely related to viruses in
      the genus Maculavirus. CONCLUSIONS: The CuTLV is a novel virus related to members
      of the family Tymoviridae, with molecular characters that are distinct from those
      of tymoviruses, marafiviruses, and other maculaviruses or macula-like viruses.
      This is the first report of the isolation of a Tymoviridae-like virus from
      mosquitoes. Further investigations are required to clarify the origin,
      replication strategy, and the public health or agricultural importance of the
      CuTLV.

PMID- 22848365
TI  - Between order and disorder: a 'weak law' on recent electoral behavior among urban
      voters?
AB  - A new viewpoint on electoral involvement is proposed from the study of the
      statistics of the proportions of abstentionists, blank and null, and votes
      according to list of choices, in a large number of national elections in
      different countries. Considering 11 countries without compulsory voting (Austria,
      Canada, Czech Republic, France, Germany, Italy, Mexico, Poland, Romania, Spain,
      and Switzerland), a stylized fact emerges for the most populated cities when one
      computes the entropy associated to the three ratios, which we call the entropy of
      civic involvement of the electorate. The distribution of this entropy (over all
      elections and countries) appears to be sharply peaked near a common value. This
      almost common value is typically shared since the 1970s by electorates of the
      most populated municipalities, and this despite the wide disparities between
      voting systems and types of elections. Performing different statistical analyses,
      we notably show that this stylized fact reveals particular correlations between
      the blank/null votes and abstentionists ratios. We suggest that the existence of
      this hidden regularity, which we propose to coin as a 'weak law on recent
      electoral behavior among urban voters', reveals an emerging collective behavioral
      norm characteristic of urban citizen voting behavior in modern democracies.
      Analyzing exceptions to the rule provides insights into the conditions under
      which this normative behavior can be expected to occur.

PMID- 22848364
TI  - Heritability estimates of body size in fetal life and early childhood.
AB  - BACKGROUND: The objective was to estimate the heritability for height and weight
      during fetal life and early childhood in two independent studies, one including
      parent and singleton offsprings and one of mono- and dizygotic twins. METHODS:
      This study was embedded in the Generation R Study (n = 3407, singletons) and the
      Netherlands Twin Register (n = 33694, twins). For the heritability estimates in
      Generation R, regression models as proposed by Galton were used. In the Twin
      Register we used genetic structural equation modelling. Parental height and
      weight were measured and fetal growth characteristics (femur length and estimated
      fetal weight) were measured by ultrasounds in 2(nd) and 3(rd) trimester
      (Generation R only). Height and weight were assessed at multiple time-points from
      birth to 36 months in both studies. RESULTS: Heritability estimates for length
      increased from 2(nd) to 3(rd) trimester from 13% to 28%. At birth, heritability
      estimates for length in singletons and twins were both 26% and 27%, respectively,
      and at 36 months, the estimates for height were 63% and 72%, respectively.
      Heritability estimates for fetal weight increased from 2(nd) to 3(rd) trimester
      from 17% to 27%. For birth weight, heritability estimates were 26% in singletons
      and 29% in twins. At 36 months, the estimate for twins was 71% and higher than
      for singletons (42%). CONCLUSIONS: Heritability estimates for height and weight
      increase from second trimester to infancy. This increase in heritability is
      observed in singletons and twins. Longer follow-up studies are needed to examine
      how the heritability develops in later childhood and puberty.

PMID- 22848366
TI  - Correlation of HER2, p95HER2 and HER3 expression and treatment outcome of
      lapatinib plus capecitabine in her2-positive metastatic breast cancer.
AB  - BACKGROUND: Lapatinib plus capecitabine is an effective treatment option for
      trastuzumab-refractory HER2-positive metastatic breast cancer. We have
      investigated the correlation between quantitative measures of HER2, p95HER2, and
      HER3 and treatment outcomes using lapatinib and capecitabine. METHODS: Total HER2
      (H2T), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin
      fixed paraffin-embedded samples using the VeraTag assays. Patients received
      lapatinib and capecitabine treatment following trastuzumab failure according to
      the Lapatinib Expanded Access Program. The association between the protein
      expression levels and clinical outcomes was analyzed. RESULTS: A total of 52
      patients were evaluable. H2T level was significantly higher in responders (median
      93.49 in partial response, 47.66 in stable disease, and 17.27 in progressive
      disease; p = 0.020). Longer time-to-progression (TTP) was observed in patients
      with high H2T [p = 0.018, median 5.2 months in high (>14.95) vs. 1.8 in low
      (<14.95)] and high H3T [p = 0.017, median 5.0 months in high (>0.605) vs. 2.2 in
      low (<0.605)]. Patients having both high H2T and high H3T had significantly
      longer TTP [adjusted hazard ratio (HR) 0.38 (95% CI 0.20-0.73), p = 0.004] and
      overall survival [adjusted HR 0.46 (95% CI 0.24-0.89), p = 0.020]. No significant
      association between p95 and response or survival was observed. CONCLUSIONS: These
      data suggest a correlation between high HER2 and high HER3 expression and
      treatment outcome, while no significant difference was observed between clinical
      outcome and p95 expression level in this cohort of HER2-positive, trastuzumab
      refractory metastatic breast cancer patients treated with lapatinib and
      capecitabine.

PMID- 22848367
TI  - Spawning of bluefin tuna in the Black Sea: historical evidence, environmental
      constraints and population plasticity.
AB  - The lucrative and highly migratory Atlantic bluefin tuna, Thunnus thynnus
      (Linnaeus 1758; Scombridae), used to be distributed widely throughout the north
      Atlantic Ocean, Mediterranean Sea and Black Sea. Its migrations have supported
      sustainable fisheries and impacted local cultures since antiquity, but its
      biogeographic range has contracted since the 1950s. Most recently, the species
      disappeared from the Black Sea in the late 1980s and has not yet recovered.
      Reasons for the Black Sea disappearance, and the species-wide range contraction,
      are unclear. However bluefin tuna formerly foraged and possibly spawned in the
      Black Sea. Loss of a locally-reproducing population would represent a decline in
      population richness, and an increase in species vulnerability to perturbations
      such as exploitation and environmental change. Here we identify the main genetic
      and phenotypic adaptations that the population must have (had) in order to
      reproduce successfully in the specific hydrographic (estuarine) conditions of the
      Black Sea. By comparing hydrographic conditions in spawning areas of the three
      species of bluefin tunas, and applying a mechanistic model of egg buoyancy and
      sinking rate, we show that reproduction in the Black Sea must have required
      specific adaptations of egg buoyancy, fertilisation and development for
      reproductive success. Such adaptations by local populations of marine fish
      species spawning in estuarine areas are common as is evident from a meta-analysis
      of egg buoyancy data from 16 species of fish. We conclude that these adaptations
      would have been necessary for successful local reproduction by bluefin tuna in
      the Black Sea, and that a locally-adapted reproducing population may have
      disappeared. Recovery of bluefin tuna in the Black Sea, either for spawning or
      foraging, will occur fastest if any remaining locally adapted individuals are
      allowed to survive, and by conservation and recovery of depleted Mediterranean
      populations which could through time re-establish local Black Sea spawning and
      foraging.

PMID- 22848368
TI  - The two-component signal transduction system ArlRS regulates Staphylococcus
      epidermidis biofilm formation in an ica-dependent manner.
AB  - Due to its ability to form biofilms on medical devices, Staphylococcus
      epidermidis has emerged as a major pathogen of nosocomial infections. In this
      study, we investigated the role of the two-component signal transduction system
      ArlRS in regulating S. epidermidis biofilm formation. An ArlRS-deficient mutant,
      WW06, was constructed using S. epidermidis strain 1457 as a parental strain.
      Although the growth curve of WW06 was similar to that of SE1457, the mutant
      strain was unable to form biofilms in vitro. In a rabbit subcutaneous infection
      model, sterile disks made of polymeric materials were implanted subcutaneously
      followed with inoculation of WW06 or SE1457. The viable bacteria cells of WW06
      recovered from biofilms on the embedded disks were much lower than that of
      SE1457. Complementation of arlRS genes expression from plasmid in WW06 restored
      biofilm-forming phenotype both in vivo and in vitro. WW06 maintained the ability
      to undergo initial attachment. Transcription levels of several genes involved in
      biofilm formation, including icaADBC, sigB, and sarA, were decreased in WW06,
      compared to SE1457; and icaR expression was increased in WW06, detected by real
      time reverse-transcription PCR. The biofilm-forming phenotype was restored by
      overexpressing icaADBC in WW06 but not by overexpressing sigB, indicating that
      ArlRS regulates biofilm formation through the regulation of icaADBC. Gel shift
      assay showed that ArlR can bind to the promoter region of the ica operon. In
      conclusion, ArlRS regulates S. epidermidis biofilm formation in an ica-dependent
      manner, distinct from its role in S. aureus.

PMID- 22848369
TI  - Concordance of gene expression and functional correlation patterns across the NCI
      60 cell lines and the Cancer Genome Atlas glioblastoma samples.
AB  - BACKGROUND: The NCI-60 is a panel of 60 diverse human cancer cell lines used by
      the U.S. National Cancer Institute to screen compounds for anticancer activity.
      We recently clustered genes based on correlation of expression profiles across
      the NCI-60. Many of the resulting clusters were characterized by cancer
      associated biological functions. The set of curated glioblastoma (GBM) gene
      expression data from the Cancer Genome Atlas (TCGA) initiative has recently
      become available. Thus, we are now able to determine which of the processes are
      robustly shared by both the immortalized cell lines and clinical cancers.
      RESULTS: Our central observation is that some sets of highly correlated genes in
      the NCI-60 expression data are also highly correlated in the GBM expression data.
      Furthermore, a "double fishing" strategy identified many sets of genes that show
      Pearson correlation >=0.60 in both the NCI-60 and the GBM data sets relative to a
      given "bait" gene. The number of such gene sets far exceeds the number expected
      by chance. CONCLUSION: Many of the gene-gene correlations found in the NCI-60 do
      not reflect just the conditions of cell lines in culture; rather, they reflect
      processes and gene networks that also function in vivo. A number of gene network
      correlations co-occur in the NCI-60 and GBM data sets, but there are others that
      occur only in NCI-60 or only in GBM. In sum, this analysis provides an additional
      perspective on both the utility and the limitations of the NCI-60 in furthering
      our understanding of cancers in vivo.

PMID- 22848370
TI  - Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma
      cells having wild type or null p53.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood. It
      accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of
      treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural
      compound, can trigger apoptosis in many cancer types. We now show that p53 is
      dispensable for Noscapine-induced cell death in neuroblastoma cell lines,
      proapoptotic response to this promising chemopreventive agent is mediated by
      suppression of survivin protein expression. The Noscapine treatment increased
      levels of total and Ser(15)-phosphorylated p53 protein in SK-SY5Y cells, but the
      proapoptotic response to this agent was maintained even after knockdown of the
      p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in
      a marked decrease in protein and mRNA level of survivin as early as 12 hours
      after treatment. Ectopic expression of survivin conferred statistically
      significant protection against Noscapine-mediated cytoplasmic histone-associated
      apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly
      but statistically significantly augmented by RNA interference of survivin in both
      cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated
      with activation of caspase-3 and cleavage of PARP. In conclusion, the present
      study provides novel insight into the molecular circuitry of Noscapine-induced
      apoptosis to indicate suppression of survivin expression as a critical mediator
      of this process.

PMID- 22848371
TI  - Hox gene expression leads to differential hind leg development between honeybee
      castes.
AB  - Beyond the physiological and behavioural, differences in appendage morphology
      between the workers and queens of Apis mellifera are pre-eminent. The hind legs
      of workers, which are highly specialized pollinators, deserve special attention.
      The hind tibia of worker has an expanded bristle-free region used for carrying
      pollen and propolis, the corbicula. In queens this structure is absent. Although
      the morphological differences are well characterized, the genetic inputs driving
      the development of this alternative morphology remain unknown. Leg phenotype
      determination takes place between the fourth and fifth larval instar and herein
      we show that the morphogenesis is completed at brown-eyed pupa. Using results
      from the hybridization of whole genome-based oligonucleotide arrays with RNA
      samples from hind leg imaginal discs of pre-pupal honeybees of both castes we
      present a list of 200 differentially expressed genes. Notably, there are castes
      preferentially expressed cuticular protein genes and members of the P450 family.
      We also provide results of qPCR analyses determining the developmental
      transcription profiles of eight selected genes, including abdominal-A, distal
      less and ultrabithorax (Ubx), whose roles in leg development have been previously
      demonstrated in other insect models. Ubx expression in workers hind leg is
      approximately 25 times higher than in queens. Finally, immunohistochemistry
      assays show that Ubx localization during hind leg development resembles the
      bristles localization in the tibia/basitarsus of the adult legs in both castes.
      Our data strongly indicate that the development of the hind legs diphenism
      characteristic of this corbiculate species is driven by a set of caste
      preferentially expressed genes, such as those encoding cuticular protein genes,
      P450 and Hox proteins, in response to the naturally different diets offered to
      honeybees during the larval period.

PMID- 22848372
TI  - Vascular disrupting agent drug classes differ in effects on the cytoskeleton.
AB  - Vascular disrupting agents (VDAs), anti-cancer drugs that target established
      tumor blood vessels, fall into two main classes: microtubule targeting drugs,
      exemplified by combretastatin A4 (CA4), and flavonoids, exemplified by 5,6
      dimethylxanthenone-4-acetic acid (DMXAA). Both classes increase permeability of
      tumor vasculature in mouse models, and DMXAA in particular can cause massive
      tumor necrosis. The molecular target of CA4 is clearly microtubules. The
      molecular target(s) of DMXAA remains unclear. It is thought to promote
      inflammatory signaling in leukocytes, and has been assumed to not target
      microtubules, though it is not clear from the literature how carefully this
      assumption has been tested. An earlier flavone analog, flavone acetic acid, was
      reported to promote mitotic arrest suggesting flavones might possess anti
      microtubule activity, and endothelial cells are sensitive to even mild disruption
      of microtubules. We carefully investigated whether DMXAA directly affects the
      microtubule or actin cytoskeletons of endothelial cells by comparing effects of
      CA4 and DMXAA on human umbilical vein endothelial cells (HUVEC) using time-lapse
      imaging and assays for cytoskeleton integrity. CA4 caused retraction of the cell
      margin, mitotic arrest and microtubule depolymerization, while DMXAA, up to 500
      uM, showed none of these effects. DMXAA also had no effect on pure tubulin
      nucleation and polymerization, unlike CA4. We conclude that DMXAA exhibits no
      direct anti-microtubule action and thus cleanly differs from CA4 in its mechanism
      of action at the molecular level.

PMID- 22848373
TI  - A new module in neural differentiation control: two microRNAs upregulated by
      retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.
AB  - The transcription factor ID2 is an important repressor of neural differentiation
      strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are
      increasingly involved in differentiation control and cancer development. Here we
      show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9
      and miR-103--restrain ID2 expression by directly targeting the coding sequence
      and 3' untranslated region of the ID2 encoding messenger RNA, respectively.
      Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma
      cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR
      103 in neuroblastoma cells reduces proliferation and promotes differentiation, as
      it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot
      be targeted by either miRNA prevents retinoic acid-induced differentiation more
      efficient than wild-type ID2. These findings reveal a new regulatory module
      involving two microRNAs upregulated during neural differentiation that directly
      target expression of the key differentiation inhibitor ID2, suggesting that its
      alteration may be involved in neural cancer development.

PMID- 22848374
TI  - Helminth antigens enable CpG-activated dendritic cells to inhibit the symptoms of
      collagen-induced arthritis through Foxp3+ regulatory T cells.
AB  - Dendritic cells (DC) have the potential to control the outcome of autoimmunity by
      modulating the immune response. In this study, we tested the ability of Fasciola
      hepatica total extract (TE) to induce tolerogenic properties in CpG-ODN (CpG)
      maturated DC, to then evaluate the therapeutic potential of these cells to
      diminish the inflammatory response in collagen induced arthritis (CIA). DBA/1J
      mice were injected with TE plus CpG treated DC (T/C-DC) pulsed with bovine
      collagen II (CII) between two immunizations with CII and clinical scores CIA were
      determined. The levels of CII-specific IgG2 and IgG1 in sera, the histological
      analyses in the joints, the cytokine profile in the draining lymph node (DLN)
      cells and in the joints, and the number, and functionality of CD4+CD25+Foxp3+ T
      cells (Treg) were evaluated. Vaccination of mice with CII pulsed T/C-DC
      diminished the severity and incidence of CIA symptoms and the production of the
      inflammatory cytokine, while induced the production of anti-inflammatory
      cytokines. The therapeutic effect was mediated by Treg cells, since the adoptive
      transfer of CD4+CD25+ T cells, inhibited the inflammatory symptoms in CIA. The in
      vitro blockage of TGF-beta in cultures of DLN cells plus CII pulsed T/C-DC
      inhibited the expansion of Treg cells. Vaccination with CII pulsed T/C-DC seems
      to be a very efficient approach to diminish exacerbated immune response in CIA,
      by inducing the development of Treg cells, and it is therefore an interesting
      candidate for a cell-based therapy for rheumatoid arthritis (RA).

PMID- 22848375
TI  - Serratia odorifera a midgut inhabitant of Aedes aegypti mosquito enhances its
      susceptibility to dengue-2 virus.
AB  - Mosquito midgut plays a crucial role in its vector susceptibility and pathogen
      interaction. Identification of the sustainable microflora of the midgut
      environment can therefore help in evaluating its contribution in mosquito
      pathogen interaction and in turn vector competence. To understand the bacterial
      diversity in the midgut of Aedes aegypti mosquitoes, we conducted a screening
      study of the gut microbes of these mosquitoes which were either collected from
      fields or reared in the laboratory "culture-dependent" approach. This work
      demonstrated that the microbial flora of larvae and adult Ae. aegypti midgut is
      complex and is dominated by gram negative proteobacteria. Serratia odorifera was
      found to be stably associated in the midguts of field collected and laboratory
      reared larvae and adult females. The potential influence of this sustainable gut
      microbe on DENV-2 susceptibility of this vector was evaluated by co-feeding S.
      odorifera with DENV-2 to adult Ae. aegypti females (free of gut flora). The
      observations revealed that the viral susceptibility of these Aedes females
      enhanced significantly as compared to solely dengue-2 fed and another gut
      inhabitant, Microbacterium oxydans co-fed females. Based on the results of this
      study we proposed that the enhancement in the DENV-2 susceptibility of Ae.
      aegypti females was due to blocking of prohibitin molecule present on the midgut
      surface of these females by the polypeptide of gut inhabitant S. odorifera.

PMID- 22848376
TI  - Streptococcus pyogenes SpyCEP influences host-pathogen interactions during
      infection in a murine air pouch model.
AB  - Streptococcus pyogenes is a major human pathogen worldwide, responsible for both
      local and systemic infections. These bacteria express the subtilisin-like
      protease SpyCEP which cleaves human IL-8 and related chemokines. We show that
      localization of SpyCEP is growth-phase and strain dependent. Significant shedding
      was observed only in a strain naturally overexpressing SpyCEP, and shedding was
      not dependent on SpyCEP autoproteolytic activity. Surface-bound SpyCEP in two
      different strains was capable of cleaving IL-8. To investigate SpyCEP action in
      vivo, we adapted the mouse air pouch model of infection for parallel
      quantification of bacterial growth, host immune cell recruitment and chemokine
      levels in situ. In response to infection, the predominant cells recruited were
      neutrophils, monocytes and eosinophils. Concomitantly, the chemokines KC, LIX,
      and MIP-2 in situ were drastically increased in mice infected with the SpyCEP
      knockout strain, and growth of this mutant strain was reduced compared to the
      wild type. SpyCEP has been described as a potential vaccine candidate against S.
      pyogenes, and we showed that surface-associated SpyCEP was recognized by specific
      antibodies. In vitro, such antibodies also counteracted the inhibitory effects of
      SpyCEP on chemokine mediated PMN recruitment. Thus, alpha-SpyCEP antibodies may
      benefit the host both directly by enabling opsonophagocytosis, and indirectly, by
      neutralizing an important virulence factor. The animal model we employed shows
      promise for broad application in the study of bacterial pathogenesis.

PMID- 22848377
TI  - Expression analysis of macrodactyly identifies pleiotrophin upregulation.
AB  - Macrodactyly is a rare family of congenital disorders characterized by the
      diffuse enlargement of 1 or more digits. Multiple tissue types within the
      affected digits are involved, but skeletal patterning and gross morphological
      features are preserved. Not all tissues are equally involved and there is marked
      heterogeneity with respect to clinical phenotype. The molecular mechanisms
      responsible for these growth disturbances offer unique insight into normal limb
      growth and development, in general. To date, no genes or loci have been
      implicated in the development of macrodactyly. In this study, we performed the
      first transcriptional profiling of macrodactyly tissue. We found that
      pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly
      samples. The mitogenic functions of PTN correlate closely with the clinical
      characteristics of macrodactyly. PTN thus represents a promising target for
      further investigation into the etiology of overgrowth phenotypes.

PMID- 22848379
TI  - Sensitization of human pancreatic cancer cells harboring mutated K-ras to
      apoptosis.
AB  - Pancreatic cancer is a devastating human malignancy and gain of functional
      mutations in K-ras oncogene is observed in 75%-90% of the patients. Studies have
      shown that oncogenic ras is not only able to promote cell growth or survival, but
      also apoptosis, depending upon circumstances. Using pancreatic cancer cell lines
      with or without expressing mutated K-ras, we demonstrated that the inhibition of
      endogenous PKC activity sensitized human pancreatic cancer cells (MIA and PANC-1)
      expressing mutated K-ras to apoptosis, which had no apoptotic effect on BxPC-3
      pancreatic cancer cells that contain a normal Ras as well as human lung
      epithelial BAES-2B cells. In this apoptotic process, the level of ROS was
      increased and PUMA was upregulated in a p73-dependent fashion in MIA and PANC-1
      cells. Subsequently, caspase-3 was cleaved. A full induction of apoptosis
      required the activation of both ROS- and p73-mediated pathways. The data suggest
      that PKC is a crucial factor that copes with aberrant K-ras to maintain the
      homeostasis of the pancreatic cancer cells harboring mutated K-ras. However, the
      suppression or loss of PKC disrupts the balance and initiates an apoptotic
      crisis, in which ROS and p73 appear the potential, key targets.

PMID- 22848378
TI  - Higher memory responses in HIV-infected and kidney transplanted patients than in
      healthy subjects following priming with the pandemic vaccine.
AB  - BACKGROUND: Memory responses require immune competence. We assessed the influence
      of priming with AS03-adjuvanted pandemic vaccine (Pandemrix(r)) on memory
      responses of HIV patients, kidney recipients (SOT) and healthy controls (HC).
      METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective
      study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1
      (HC) or 2 (patients) doses of Pandemrix(r), and were boosted with the 2010/2011
      seasonal influenza vaccine. Geometric mean titres and seroprotection rates were
      measured 12 months after priming and 4 weeks after boosting. Primary and memory
      responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51)
      followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%,
      HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming.
      Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in
      SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than
      in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced
      persisting and memory responses, mainly influenced by residual antibody titers.
      Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2
      seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher
      titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS:
      Priming with 2 doses of Pandemrix(r) elicited persistent antibody responses and
      even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients
      than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory
      responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01022905.

PMID- 22848380
TI  - Genomic assessment of human cumulus cell marker genes as predictors of oocyte
      developmental competence: impact of various experimental factors.
AB  - BACKGROUND: Single embryo transfer (SET) is the most successful way to reduce the
      frequency of multiple pregnancies following in vitro fertilisation. However,
      selecting the embryo for SET with the highest chances of pregnancy remains a
      difficult challenge since morphological and kinetics criteria provide poor
      prediction of both developmental and implantation ability. Partly through the
      expression of specific genes, the oocyte-cumulus interaction helps the oocyte to
      acquire its developmental competence. Our aim was therefore to identify at the
      level of cumulus cells (CCs) genes related to oocyte developmental competence.
      METHODOLOGY/PRINCIPAL FINDINGS: 197 individual CCs were collected from 106
      patients undergoing an intra-cytoplasmic sperm injection procedure. Gene
      expression of CCs was studied using microarray according to the nuclear maturity
      of the oocyte (immature vs. mature oocyte) and to the developmental competence of
      the oocyte (ability to reach the blastocyst stage after fertilisation).
      Microarray study was followed by a meta-analysis of the behaviour of these genes
      in other datasets available in Gene Expression Omnibus which showed the
      consistency of this list of genes. Finally, 8 genes were selected according to
      oocyte developmental competence from the 308 differentially expressed genes
      (p<0.0001) for further validation by quantitative PCR (qPCR). Three of these 8
      selected genes were validated as potential biomarkers (PLIN2, RGS2 and ANG).
      Experimental factors such as inter-patient and qPCR series variability were then
      assessed using the Generalised Linear Mixed Model procedure, and only the
      expression level of RGS2 was confirmed to be related to oocyte developmental
      competence. The link between biomarkers and pregnancy was finally evaluated and
      level of RGS2 expression was also correlated with clinical pregnancy.
      CONCLUSION/SIGNIFICANCE: RGS2, known as a regulator of G protein signalling, was
      the only gene among our 8 selected candidates biomarkers of oocyte competence to
      cover many factors of variability, including inter-patient factors and
      experimental conditions.

PMID- 22848381
TI  - Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial
      mesenchymal transition.
AB  - BACKGROUND: Metastasis is the major cause of cancer related death and targeting
      the process of metastasis has been proposed as a strategy to combat cancer.
      Therefore, to develop candidate drugs that target the process of metastasis is
      very important. In the preliminary studies, we found that schisandrin B (Sch B),
      a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could
      suppress cancer metastasis. METHODOLOGY: BALB/c mice were inoculated
      subcutaneously or injected via tail vein with murine breast cancer 4T1 cells.
      Mice were divided into Sch B-treated and control groups. The primary tumor
      growth, local invasion, lung and bone metastasis, and survival time were
      monitored. Tumor biopsies were examined immuno- and histo-pathologically. The
      inhibitory activity of Sch B on TGF-beta induced epithelial-mesenchymal
      transition (EMT) of 4T1 and primary human breast cancer cells was assayed.
      PRINCIPAL FINDINGS: Sch B significantly suppressed the spontaneous lung and bone
      metastasis of 4T1 cells inoculated s.c. without significant effect on primary
      tumor growth and significantly extended the survival time of these mice. Sch B
      did not inhibit lung metastasis of 4T1 cells that were injected via tail vein.
      Delayed start of treatment with Sch B in mice with pre-existing tumors did not
      reduce lung metastasis. These results suggested that Sch B acted at the step of
      local invasion. Histopathological evidences demonstrated that the primary tumors
      in Sch B group were significantly less locally invasive than control tumors. In
      vitro assays demonstrated that Sch B could inhibit TGF-beta induced EMT of 4T1
      cells and of primary human breast cancer cells. CONCLUSIONS: Sch B significantly
      suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT,
      suggesting its potential application in targeting the process of cancer
      metastasis.

PMID- 22848382
TI  - Hunter-gatherer energetics and human obesity.
AB  - Western lifestyles differ markedly from those of our hunter-gatherer ancestors,
      and these differences in diet and activity level are often implicated in the
      global obesity pandemic. However, few physiological data for hunter-gatherer
      populations are available to test these models of obesity. In this study, we used
      the doubly-labeled water method to measure total daily energy expenditure
      (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy
      each day than their Western counterparts. As expected, physical activity level,
      PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average
      daily energy expenditure of traditional Hadza foragers was no different than that
      of Westerners after controlling for body size. The metabolic cost of walking
      (kcal kg(-1) m(-1)) and resting (kcal kg(-1) s(-1)) were also similar among Hadza
      and Western groups. The similarity in metabolic rates across a broad range of
      cultures challenges current models of obesity suggesting that Western lifestyles
      lead to decreased energy expenditure. We hypothesize that human daily energy
      expenditure may be an evolved physiological trait largely independent of cultural
      differences.

PMID- 22848383
TI  - Mining GO annotations for improving annotation consistency.
AB  - Despite the structure and objectivity provided by the Gene Ontology (GO), the
      annotation of proteins is a complex task that is subject to errors and
      inconsistencies. Electronically inferred annotations in particular are widely
      considered unreliable. However, given that manual curation of all GO annotations
      is unfeasible, it is imperative to improve the quality of electronically inferred
      annotations. In this work, we analyze the full GO molecular function annotation
      of UniProtKB proteins, and discuss some of the issues that affect their quality,
      focusing particularly on the lack of annotation consistency. Based on our
      analysis, we estimate that 64% of the UniProtKB proteins are incompletely
      annotated, and that inconsistent annotations affect 83% of the protein functions
      and at least 23% of the proteins. Additionally, we present and evaluate a data
      mining algorithm, based on the association rule learning methodology, for
      identifying implicit relationships between molecular function terms. The goal of
      this algorithm is to assist GO curators in updating GO and correcting and
      preventing inconsistent annotations. Our algorithm predicted 501 relationships
      with an estimated precision of 94%, whereas the basic association rule learning
      methodology predicted 12,352 relationships with a precision below 9%.

PMID- 22848384
TI  - How do children solve Aesop's Fable?
AB  - Studies on members of the crow family using the "Aesop's Fable" paradigm have
      revealed remarkable abilities in these birds, and suggested a mechanism by which
      associative learning and folk physics may interact when learning new problems. In
      the present study, children between 4 and 10 years of age were tested on the same
      tasks as the birds. Overall the performance of the children between 5-7-years was
      similar to that of the birds, while children from 8-years were able to succeed in
      all tasks from the first trial. However the pattern of performance across tasks
      suggested that different learning mechanisms might be being employed by children
      than by adult birds. Specifically, it is possible that in children, unlike
      corvids, performance is not affected by counter-intuitive mechanism cues.

PMID- 22848385
TI  - The A2b adenosine receptor modulates glucose homeostasis and obesity.
AB  - BACKGROUND: High fat diet and its induced changes in glucose homeostasis,
      inflammation and obesity continue to be an epidemic in developed countries. The
      A2b adenosine receptor (A2bAR) is known to regulate inflammation. We used a diet
      induced obesity murine knockout model to investigate the role of this receptor in
      mediating metabolic homeostasis, and correlated our findings in obese patient
      samples. METHODOLOGY/PRINCIPAL FINDINGS: Administration of high fat, high
      cholesterol diet (HFD) for sixteen weeks vastly upregulated the expression of the
      A2bAR in control mice, while A2bAR knockout (KO) mice under this diet developed
      greater obesity and hallmarks of type 2 diabetes (T2D), assessed by delayed
      glucose clearance and augmented insulin levels compared to matching control mice.
      We identified a novel link between the expression of A2bAR, insulin receptor
      substrate 2 (IRS-2), and insulin signaling, determined by Western blotting for
      IRS-2 and tissue Akt phosphorylation. The latter is impaired in tissues of A2bAR
      KO mice, along with a greater inflammatory state. Additional mechanisms involved
      include A2bAR regulation of SREBP-1 expression, a repressor of IRS-2.
      Importantly, pharmacological activation of the A2bAR by injection of the A2bAR
      ligand BAY 60-6583 for four weeks post HFD restores IRS-2 levels, and ameliorates
      T2D. Finally, in obese human subjects A2bAR expression correlates strongly with
      IRS-2 expression. CONCLUSIONS/SIGNIFICANCE: Our study identified the A2bAR as a
      significant regulator of HFD-induced hallmarks of T2D, thereby pointing to its
      therapeutic potential.

PMID- 22848386
TI  - Fast recruitment of recurrent inhibition in the cat visual cortex.
AB  - Neurons of the same column in L4 of the cat visual cortex are likely to share the
      same sensory input from the same region of the visual field. Using visually
      guided patch clamp recordings we investigated the biophysical properties of the
      synapses of neighboring layer 4 neurons. We recorded synaptic connections between
      all types of excitatory and inhibitory neurons in L4. The E-E, E-I, and I-E
      connections had moderate CVs and failure rates. However, E-I connections had
      larger amplitudes, faster rise-times, and shorter latencies. Identification of
      the sites of putative synaptic contacts together with compartmental simulations
      on 3D reconstructed cells, suggested that E-I synapses tended to be located on
      proximal dendritic branches, which would explain their larger EPSP amplitudes and
      faster kinetics. Excitatory and inhibitory synapses were located at the same
      distance on distal dendrites of excitatory neurons. We hypothesize that this co
      localization and the fast recruitment of local inhibition provides an efficient
      means of modulating excitation in a precisely timed way.

PMID- 22848387
TI  - Low serum urate levels are associated to female gender in multiple sclerosis
      patients.
AB  - BACKGROUND: Urate is a natural antioxidant and may prevent CNS tissue damage and
      the clinical manifestations of experimental autoimmune encephalitis. Results from
      clinical studies are conflicting and the contribution of urate to the
      pathogenesis of Multiple Sclerosis (MS) remains uncertain. OBJECTIVE: To evaluate
      serum urate levels in MS patients and their relationships with clinical,
      demographic and MRI variables. METHODS: Levels of non-fasting serum uric acid and
      creatinine were determined by an automated enzymatic assay and glomerular
      filtration rate was assessed in 245 MS patients, in 252 age/sex-matched
      neurological controls (NC) and in 59 Healthy controls (HC). RESULTS: Median serum
      urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and
      NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all
      groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower
      compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02),
      whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5
      mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically
      isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL),
      compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients
      with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR <=2:
      3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females
      than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female
      sex (beta: -0.53; p<0.00001) was the most significant determinant of serum urate
      concentrations in MS patients on multivariate regression analysis. CONCLUSIONS:
      Our findings suggest that low urate levels could be of significance in
      predominantly inflammatory phases of MS even at the early stage and mainly in
      females.

PMID- 22848388
TI  - Retinal ganglion cell loss is accompanied by antibody depositions and increased
      levels of microglia after immunization with retinal antigens.
AB  - BACKGROUND: Antibodies against retinal and optic nerve antigens are detectable in
      glaucoma patients. Recent studies using a model of experimental autoimmune
      glaucoma demonstrated that immunization with certain ocular antigens causes an
      immun-mediated retinal ganglion cell loss in rats. METHODOLOGY/PRINCIPAL
      FINDINGS: Rats immunized with a retinal ganglion cell layer homogenate (RGA) had
      a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a
      lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The
      autoreactive antibody development against retina and optic nerve was examined
      throughout the study. The levels of autoreactive antibodies continuously
      increased up to 6 weeks (retina: p = 0.004; optic nerve: p = 0.000003).
      Additionally, antibody deposits were detected in the retina (p = 0.02). After 6
      weeks a reactive gliosis (GFAP density: RGA: 174.7+/-41.9; CO: 137.6+/-36.8, p =
      0.0006; %GFAP(+) area: RGA: 8.5+/-3.4; CO: 5.9+/-3.6, p = 0.006) as well as
      elevated level of Iba1(+) microglia cells (p = 0.003) was observed in retinas of
      RGA animals. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that these antibodies
      play a substantial role in mechanisms leading to retinal ganglion cell death.
      This seems to lead to glia cell activation as well as the invasion of microglia,
      which might be associated with debris clearance.

PMID- 22848389
TI  - An effort to use human-based exome capture methods to analyze chimpanzee and
      macaque exomes.
AB  - Non-human primates have emerged as an important resource for the study of human
      disease and evolution. The characterization of genomic variation between and
      within non-human primate species could advance the development of genetically
      defined non-human primate disease models. However, non-human primate specific
      reagents that would expedite such research, such as exon-capture tools, are
      lacking. We evaluated the efficiency of using a human exome capture design for
      the selective enrichment of exonic regions of non-human primates. We compared the
      exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight
      Japanese macaques. Over 91% of the target regions were captured in the non-human
      primate samples, although the specificity of the capture decreased as
      evolutionary divergence from humans increased. Both intra-specific and inter
      specific DNA variants were identified; Sanger-based resequencing validated 85.4%
      of 41 randomly selected SNPs. Among the short indels identified, a majority
      (54.6%-77.3%) of the variants resulted in a change of 3 base pairs, consistent
      with expectations for a selection against frame shift mutations. Taken together,
      these findings indicate that use of a human design exon-capture array can provide
      efficient enrichment of non-human primate gene regions. Accordingly, use of the
      human exon-capture methods provides an attractive, cost-effective approach for
      the comparative analysis of non-human primate genomes, including gene-based DNA
      variant discovery.

PMID- 22848390
TI  - Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic
      preconditioning and is associated with decreased Il-6/STAT3 signaling.
AB  - OBJECTIVE: Recent studies indicate that the innate immune system is not only
      triggered by exogenous pathogens and pollutants, but also by endogenous danger
      signals released during ischemia and necrosis. As triggers for the innate immune
      NLRP3 inflammasome protein complex appear to overlap with those for cardiac
      ischemia-reperfusion (I/R) and ischemic preconditioning (IPC), we explored the
      possibility that the NLRP3 inflammasome is involved in IPC and acute I/R injury
      of the heart. PRINCIPAL FINDINGS: Baseline cardiac performance and acute I/R
      injury were investigated in isolated, Langendorff-perfused hearts from wild-type
      (WT), ASC(-/-) and NLRP3(-/-) mice. Deletion of NLRP3 inflammasome components
      ASC(-/-) or NLRP3(-/-) did not affect baseline performance. The deletions
      exacerbated I/R-induced mechanical dysfunction, but were without effect on I/R
      induced cell death. When subjected to IPC, WT and ASC(-/-) hearts were protected
      against I/R injury (improved function and less cell death). However, IPC did not
      protect NLRP3(-/-) hearts against I/R injury. NLRP3(-/-) hearts had significantly
      decreased cardiac IL-6 levels with a trend towards lower IL-1beta levels at end
      reperfusion, suggesting abrogation of IPC through diminished IL-6 and/or IL-1beta
      signaling. Subsequent experiments showed that neutralising IL-6 using an antibody
      against IL-6 abrogated IPC in WT hearts. However, inhibition of the IL-1r
      receptor with the IL-1 receptor inhibitor Anakinra (100 mg/L) did not abrogate
      IPC in WT hearts. Analysis of survival kinases after IPC demonstrated decreased
      STAT3 expression in NLRP3(-/-) hearts when compared to WT hearts. CONCLUSIONS:
      The data suggest that the innate immune NLRP3 protein, in an NLRP3-inflammasome
      independent fashion, is an integral component of IPC in the isolated heart,
      possibly through an IL-6/STAT3 dependent mechanism.

PMID- 22848391
TI  - Modulation of intestinal inflammation by yeasts and cell wall extracts: strain
      dependence and unexpected anti-inflammatory role of glucan fractions.
AB  - Yeasts and their glycan components can have a beneficial or adverse effect on
      intestinal inflammation. Previous research has shown that the presence of
      Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and
      colonization by Candida albicans. The aim of this study was to identify dietary
      yeasts, which have comparable effects to the anti-C. albicans and anti
      inflammatory properties of Sb and to assess the capabilities of yeast cell wall
      components to modulate intestinal inflammation. Mice received a single oral
      challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS)
      for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb,
      Sc1 to Sc4), as well as mannoprotein (MP) and beta-glucan crude fractions
      prepared from Sc2 and highly purified beta-glucans prepared from C. albicans were
      used in this curative model, starting 3 days after C. albicans challenge. Mice
      were assessed for the clinical, histological and inflammatory responses related
      to DSS administration. Strain Sc1-1 gave the same level of protection against C.
      albicans as Sb when assessed by mortality, clinical scores, colonization levels,
      reduction of TNFalpha and increase in IL-10 transcription. When Sc1-1 was
      compared with the other S. cerevisiae strains, the preparation process had a
      strong influence on biological activity. Interestingly, some S. cerevisiae
      strains dramatically increased mortality and clinical scores. Strain Sc4 and MP
      fraction favoured C. albicans colonization and inflammation, whereas beta-glucan
      fraction was protective against both. Surprisingly, purified beta-glucans from C.
      albicans had the same protective effect. Thus, some yeasts appear to be strong
      modulators of intestinal inflammation. These effects are dependent on the strain,
      species, preparation process and cell wall fraction. It was striking that beta
      glucan fractions or pure beta-glucans from C. albicans displayed the most potent
      anti-inflammatory effect in the DSS model.

PMID- 22848392
TI  - Downregulation of the NHE3-binding PDZ-adaptor protein PDZK1 expression during
      cytokine-induced inflammation in interleukin-10-deficient mice.
AB  - BACKGROUND: Impaired salt and water absorption is an important feature in the
      pathogenesis of diarrhea in inflammatory bowel disease (IBD). We analyzed the
      expression of proinflammatory cytokines in the infiltrating immune cells and the
      function and expression of the Na(+)/H(+) exchanger isoform 3 (NHE3) and its
      regulatory PDZ-adaptor proteins NHERF1, NHERF2, and PDZK1 in the colon of
      interleukin-10-deficient (IL-10(-/-)) mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene
      and protein expression were analyzed by real-time reverse transcription
      polymerase chain reaction (qRT-PCR), in situ RT-PCR, and immunohistochemistry.
      NHE3 activity was measured fluorometrically in apical enterocytes within isolated
      colonic crypts. Mice developed chronic colitis characterized by a typical immune
      cell infiltration composed of T-lymphocytes and macrophages, with high levels of
      gene and protein expression of the proinflammatory cytokines interleukin-1beta
      and tumor necrosis factor-alpha. In parallel, inducible nitric oxide synthase
      expression was increased while procaspase 3 expression was unaffected. Interferon
      gamma expression remained low. Although acid-activated NHE3 activity was
      significantly decreased, the inflammatory process did not affect its gene and
      protein expression or its abundance and localization in the apical membrane.
      However, expression of the PDZ-adaptor proteins NHERF2 and PDZK1 was
      downregulated. NHERF1 expression was unchanged. In a comparative analysis we
      observed the PDZK1 downregulation also in the DSS (dextran sulphate sodium) model
      of colitis. CONCLUSIONS/SIGNIFICANCE: The impairment of the absorptive function
      of the inflamed colon in the IL-10(-/-) mouse, in spite of unaltered NHE3
      expression and localization, is accompanied by the downregulation of the NHE3
      regulatory PDZ adaptors NHERF2 and PDZK1. We propose that the downregulation of
      PDZ-adaptor proteins may be an important factor leading to NHE3 dysfunction and
      diarrhea in the course of the cytokine-mediated inflammatory process in these
      animal models of IBD.

PMID- 22848393
TI  - Risks associated with high-dose Lactobacillus rhamnosus in an Escherichia coli
      model of piglet diarrhoea: intestinal microbiota and immune imbalances.
AB  - Probiotic could be a promising alternative to antibiotics for the prevention of
      enteric infections; however, further information on the dose effects is required.
      In this study, weanling piglets were orally administered low- or high-dose
      Lactobacillus rhamnosus ACTT 7469 (10(10) CFU/d or 10(12) CFU/d) for 1 week
      before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal
      and gastrointestinal microbiota were recorded; gene expression in the intestines
      was assessed by real-time PCR; serum tumour necrosis factor-alpha (TNF-alpha)
      concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA
      and immunohistochemistry, respectively. Unexpectedly, high-dose administration
      increased the incidence of diarrhoea before F4(+)ETEC challenge, despite the fact
      that both doses ameliorated F4(+)ETEC-induced diarrhoea with increased
      Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding
      in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and
      Bifidobacterium counts in the colonic contents, and the high-dose piglets also
      had lower Lactobacillius and Bacteroides counts in the ileal contents. An
      increase in the concentration of serum TNF-alpha induced by F4(+)ETEC was
      observed, but the increase was delayed by L. rhamnosus. In piglets exposed to
      F4(+)ETEC, jejunal TLR4 expression increased at the mRNA and protein levels,
      while jejunal interleukin (IL)-8 and ileal porcine beta-defensins 2 (pBD2) mRNA
      expression increased; however, these increases were attenuated by administration
      of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like
      receptor NOD1 and TNF-alpha mRNA was upregulated in the low-dose piglets after
      F4(+)ETEC challenge, but not in the high-dose piglets. These findings indicate
      that pretreatment with a low dose of L. rhamnosus might be more effective than a
      high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus
      pretreatment may negate the preventative effects, thus decreasing the
      prophylactic benefits against potential enteric pathogens. Our data suggest a
      safe threshold for preventative use of probiotics in clinical practice.

PMID- 22848394
TI  - Dynamics of PLCgamma and Src family kinase 1 interactions during nuclear envelope
      formation revealed by FRET-FLIM.
AB  - The nuclear envelope (NE) breaks down and reforms during each mitotic cycle. A
      similar process happens to the sperm NE following fertilisation. The formation of
      the NE in both these circumstances involves endoplasmic reticulum membranes
      enveloping the chromatin, but PLCgamma-dependent membrane fusion events are also
      essential. Here we demonstrate the activation of PLCgamma by a Src family kinase
      (SFK1) during NE assembly. We show by time-resolved FRET for the first time the
      direct in vivo interaction and temporal regulation of PLCgamma and SFK1 in sea
      urchins. As a prerequisite for protein activation, there is a rapid
      phosphorylation of PLCgamma on its Y783 residue in response to GTP in vitro. This
      phosphorylation is dependent upon SFK activity; thus Y783 phosphorylation and NE
      assembly are susceptible to SFK inhibition. Y783 phosphorylation is also observed
      on the surface of the male pronucleus (MPN) in vivo during NE formation. Together
      the corroborative in vivo and in vitro data demonstrate the phosphorylation and
      activation of PLCgamma by SFK1 during NE assembly. We discuss the potential
      generality of such a mechanism.

PMID- 22848395
TI  - Repeat tracking of individual songbirds reveals consistent migration timing but
      flexibility in route.
AB  - Tracking repeat migratory journeys of individual animals is required to assess
      phenotypic plasticity of individual migration behaviour in space and time. We
      used light-level geolocators to track the long-distance journeys of migratory
      songbirds (wood thrush, Hylocichla mustelina), and, for the first time, repeat
      journeys of individuals. We compare between- and within-individual variation in
      migration to examine flexibility of timing and route in spring and autumn. Date
      of departure from wintering sites in Central America, along with sex and age
      factors, explained most of the variation (71%) in arrival date at North American
      breeding sites. Spring migration showed high within-individual repeatability in
      timing, but not in route. In particular, spring departure dates of individuals
      were highly repeatable, with a mean difference between years of just 3 days.
      Autumn migration timing and routes were not repeatable. Our results provide novel
      evidence of low phenotypic plasticity in timing of spring migration, which may
      limit the ability of individuals to adjust migration schedules in response to
      climate change.

PMID- 22848396
TI  - Identification of quiescent, stem-like cells in the distal female reproductive
      tract.
AB  - In fertile women, the endometrium undergoes regular cycles of tissue build-up and
      regression. It is likely that uterine stem cells are involved in this remarkable
      turn over. The main goal of our current investigations was to identify slow
      cycling (quiescent) endometrial stem cells by means of a pulse-chase approach to
      selectively earmark, prospectively isolate, and characterize label-retaining
      cells (LRCs). To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP) in
      a Tet-inducible fashion were administered doxycycline (pulse) which was
      thereafter withdrawn from the drinking water (chase). Over time, dividing cells
      progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP
      expression. We evaluated H2B-GFP retaining cells at different chase time points
      and identified long-term (LT; >12 weeks) LRCs. The LT-LRCs are negative for
      estrogen receptor-alpha and express low levels of progesterone receptors. LRCs
      sorted by FACS are able to form spheroids capable of self-renewal and
      differentiation. Upon serum stimulation spheroid cells are induced to
      differentiate and form glandular structures which express markers of mature
      mullerian epithelial cells. Overall, the results indicate that quiescent cells
      located in the distal oviduct have stem-like properties and can differentiate
      into distinct cell lineages specific of endometrium, proximal and distal oviduct.
      Future lineage-tracing studies will elucidate the role played by these cells in
      homeostasis, tissue injury and cancer of the female reproductive tract in the
      mouse and eventually in man.

PMID- 22848397
TI  - Solution structure of the LIM-homeodomain transcription factor complex Lhx3/Ldb1
      and the effects of a pituitary mutation on key Lhx3 interactions.
AB  - Lhx3 is a LIM-homeodomain (LIM-HD) transcription factor that regulates neural
      cell subtype specification and pituitary development in vertebrates, and
      mutations in this protein cause combined pituitary hormone deficiency syndrome
      (CPHDS). The recently published structures of Lhx3 in complex with each of two
      key protein partners, Isl1 and Ldb1, provide an opportunity to understand the
      effect of mutations and posttranslational modifications on key protein-protein
      interactions. Here, we use small-angle X-ray scattering of an Ldb1-Lhx3 complex
      to confirm that in solution the protein is well represented by our previously
      determined NMR structure as an ensemble of conformers each comprising two well
      defined halves (each made up of LIM domain from Lhx3 and the corresponding
      binding motif in Ldb1) with some flexibility between the two halves. NMR analysis
      of an Lhx3 mutant that causes CPHDS, Lhx3(Y114C), shows that the mutation does
      not alter the zinc-ligation properties of Lhx3, but appears to cause a structural
      rearrangement of the hydrophobic core of the LIM2 domain of Lhx3 that
      destabilises the domain and/or reduces the affinity of Lhx3 for both Ldb1 and
      Isl1. Thus the mutation would affect the formation of Lhx3-containing
      transcription factor complexes, particularly in the pituitary gland where these
      complexes are required for the production of multiple pituitary cell types and
      hormones.

PMID- 22848399
TI  - Cultural differences in investing in others and in the future: why measuring
      trust is not enough.
AB  - Standard measures of generalized trust in others are often taken to provide
      reliable indicators of economic attitudes in different countries. Here we
      compared three highly distinct groups, in Kenya, China and the US, in terms of
      more specific attitudes, [a] people's willingness to invest in the future, [b]
      their willingness to invest in others, and [c] their trust in institutions.
      Results suggest that these measures capture deep differences in economic
      attitudes that are not detected by standard measures of generalized trust.

PMID- 22848398
TI  - Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets
      of T-cell lymphoblastic leukemia (T-ALL).
AB  - Homeobox genes encode transcription factors impacting key developmental processes
      including embryogenesis, organogenesis, and cell differentiation. Reflecting
      their tight transcriptional control, homeobox genes are often embedded in large
      non-coding, cis-regulatory regions, containing tissue specific elements. In T
      cell acute lymphoblastic leukemia (T-ALL) homeobox genes are frequently
      deregulated by chromosomal aberrations, notably translocations adding T-cell
      specific activatory elements. NKX3-1 is a prostate specific homeobox gene
      activated in T-ALL patients expressing oncogenic TAL1 or displaying immature T
      cell characteristics. After investigating regulation of NKX3-1 in primary cells
      and cell lines, we report its ectopic expression in T-ALL cells independent of
      chromosomal rearrangements. Using siRNAs and expression profiling, we exploited
      NKX3-1 positive T-ALL cell lines as tools to investigate aberrant activatory
      mechanisms. Our data confirmed NKX3-1 activation by TAL1/GATA3/LMO and identified
      LYL1 as an alternative activator in immature T-ALL cells devoid of GATA3.
      Moreover, we showed that NKX3-1 is directly activated by early T-cell homeodomain
      factor MSX2. These activators were regulated by MLL and/or by IL7-, BMP4- and
      IGF2-signalling. Finally, we demonstrated homeobox gene SIX6 as a direct leukemic
      target of NKX3-1 in T-ALL. In conclusion, we identified three major mechanisms of
      NKX3-1 regulation in T-ALL cell lines which are represented by activators TAL1,
      LYL1 and MSX2, corresponding to particular T-ALL subtypes described in patients.
      These results may contribute to the understanding of leukemic transcriptional
      networks underlying disturbed T-cell differentiation in T-ALL.

PMID- 22848400
TI  - Therapeutic inhibition of pro-inflammatory signaling and toxicity to
      staphylococcal enterotoxin B by a synthetic dimeric BB-loop mimetic of MyD88.
AB  - Staphylococcal enterotoxin B (SEB) exposure triggers an exaggerated pro
      inflammatory cytokine response that often leads to toxic shock syndrome (TSS)
      associated with organ failure and death. MyD88 mediates pro-inflammatory cytokine
      signaling induced by SEB exposure and MyD88(-/-) mice are resistant to SEB
      intoxication, suggesting that MyD88 may be a potential target for therapeutic
      intervention. We targeted the BB loop region of the Toll/IL-1 receptor (TIR)
      domain of MyD88 to develop small-molecule therapeutics. Here, we report that a
      synthetic compound (EM-163), mimic to dimeric form of BB-loop of MyD88 attenuated
      tumor necrosis factor (TNF)- alpha, interferon (IFN)-gamma, interleukin (IL)
      1beta, IL-2 and IL-6 production in human primary cells, whether administered pre-
      or post-SEB exposure. Results from a direct binding assay, and from MyD88 co
      transfection/co-immunoprecipitation experiments, suggest that EM-163 inhibits TIR
      TIR domain interaction. Additional results indicate that EM-163 prevents MyD88
      from mediating downstream signaling. In an NF-kB-driven reporter assay of
      lipopolysaccharide-stimulated MyD88 signaling, EM-163 demonstrated a dose
      dependent inhibition of reporter activity as well as TNF-alpha and IL-1beta
      production. Importantly, administration of EM-163 pre- or post exposure to a
      lethal dose of SEB abrogated pro-inflammatory cytokine responses and protected
      mice from toxic shock-induced death. Taken together, our results suggest that EM
      163 exhibits a potential for therapeutic use against SEB intoxication.

PMID- 22848401
TI  - Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity
      with non-communicable diseases in sputum producing adult inpatients.
AB  - BACKGROUND: A high burden of tuberculosis (TB) occurs in sub-Saharan African
      countries and many cases of active TB and drug-resistant TB remain undiagnosed.
      Tertiary care hospitals provide an opportunity to study TB co-morbidity with non
      communicable and other communicable diseases (NCDs/CDs). We evaluated the burden
      of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients,
      regardless of their primary admission diagnosis, in a tertiary referral centre.
      METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study, newly admitted adult
      inpatients able to produce sputum at the University Teaching Hospital, Lusaka,
      Zambia, were screened for pulmonary TB using fluorescent smear microscopy and
      automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co
      morbidity with NCDs and CDs was determined. Sputum was analysed from 900
      inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB
      suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of
      patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%)
      NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI:
      1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed
      cases of MDR-TB, 5 of which were unsuspected. CONCLUSIONS/SIGNIFICANCE: A large
      burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs
      and other CDs. Pro-active sputum screening of all inpatients in tertiary referral
      centres in high TB endemic countries is recommended. The scale of the problem of
      undiagnosed MDR-TB in inpatients requires further study.

PMID- 22848402
TI  - Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal
      amino acid motif.
AB  - Hsp90 is an essential chaperone that is necessary for the folding, stability and
      activity of numerous proteins. In this study, we demonstrate that free radicals
      formed during oxidative stress conditions can cleave Hsp90. This cleavage occurs
      through a Fenton reaction which requires the presence of redox-active iron. As a
      result of the cleavage, we observed a disruption of the chaperoning function of
      Hsp90 and the degradation of its client proteins, for example, Bcr-Abl, RIP, c
      Raf, NEMO and hTert. Formation of Hsp90 protein radicals on exposure to oxidative
      stress was confirmed by immuno-spin trapping. Using a proteomic analysis, we
      determined that the cleavage occurs in a conserved motif of the N-terminal
      nucleotide binding site, between Ile-126 and Gly-127 in Hsp90beta, and between
      Ile-131 and Gly-132 in Hsp90alpha. Given the importance of Hsp90 in diverse
      biological functions, these findings shed new light on how oxidative stress can
      affect cellular homeostasis.

PMID- 22848403
TI  - Retroactive signaling in short signaling pathways.
AB  - In biochemical signaling pathways without explicit feedback connections, the core
      signal transduction is usually described as a one-way communication, going from
      upstream to downstream in a feedforward chain or network of covalent modification
      cycles. In this paper we explore the possibility of a new type of signaling
      called retroactive signaling, offered by the recently demonstrated property of
      retroactivity in signaling cascades. The possibility of retroactive signaling is
      analysed in the simplest case of the stationary states of a bicyclic cascade of
      signaling cycles. In this case, we work out the conditions for which variables of
      the upstream cycle are affected by a change of the total amount of protein in the
      downstream cycle, or by a variation of the phosphatase deactivating the same
      protein. Particularly, we predict the characteristic ranges of the downstream
      protein, or of the downstream phosphatase, for which a retroactive effect can be
      observed on the upstream cycle variables. Next, we extend the possibility of
      retroactive signaling in short but nonlinear signaling pathways involving a few
      covalent modification cycles.

PMID- 22848404
TI  - Prediction of carbohydrate binding sites on protein surfaces with 3-dimensional
      probability density distributions of interacting atoms.
AB  - Non-covalent protein-carbohydrate interactions mediate molecular targeting in
      many biological processes. Prediction of non-covalent carbohydrate binding sites
      on protein surfaces not only provides insights into the functions of the query
      proteins; information on key carbohydrate-binding residues could suggest site
      directed mutagenesis experiments, design therapeutics targeting carbohydrate
      binding proteins, and provide guidance in engineering protein-carbohydrate
      interactions. In this work, we show that non-covalent carbohydrate binding sites
      on protein surfaces can be predicted with relatively high accuracy when the query
      protein structures are known. The prediction capabilities were based on a novel
      encoding scheme of the three-dimensional probability density maps describing the
      distributions of 36 non-covalent interacting atom types around protein surfaces.
      One machine learning model was trained for each of the 30 protein atom types. The
      machine learning algorithms predicted tentative carbohydrate binding sites on
      query proteins by recognizing the characteristic interacting atom distribution
      patterns specific for carbohydrate binding sites from known protein structures.
      The prediction results for all protein atom types were integrated into surface
      patches as tentative carbohydrate binding sites based on normalized prediction
      confidence level. The prediction capabilities of the predictors were benchmarked
      by a 10-fold cross validation on 497 non-redundant proteins with known
      carbohydrate binding sites. The predictors were further tested on an independent
      test set with 108 proteins. The residue-based Matthews correlation coefficient
      (MCC) for the independent test was 0.45, with prediction precision and
      sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound
      carbohydrate-binding protein structures for which the structures were determined
      in the absence of the carbohydrate ligands were predicted with the trained
      predictors. The overall prediction MCC was 0.49. Independent tests on anti
      carbohydrate antibodies showed that the carbohydrate antigen binding sites were
      predicted with comparable accuracy. These results demonstrate that the predictors
      are among the best in carbohydrate binding site predictions to date.

PMID- 22848405
TI  - Comparison of apolipoprotein (apoB/apoA-I) and lipoprotein (total
      cholesterol/HDL) ratio determinants. Focus on obesity, diet and alcohol intake.
AB  - The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been
      suggested to be a powerful and more accurate predictor of future cardiovascular
      disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle
      can directly influence dyslipidemia, it is of interest to identify modifiable
      factors that are associated with high levels of the apolipoprotein ratio and if
      they can have a different association with a more traditional indicator of
      cardiovascular risk such as total cholesterol/HDL. The relationship between
      obesity and dyslipidemia is established and it is of interest to determine which
      factors can modify this association. This study investigated the cross-sectional
      association of obesity, diet and lifestyle factors with apoB/apoA-I and total
      cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537
      women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios
      were highly correlated, particularly in women, and obesity was strongly
      associated with both. Additionally, age, cigarette smoking and alcohol intake
      were important determinants of these ratios. Alcohol was the only dietary factor
      that appreciably attenuated the association between obesity and each of the
      ratios, with a stronger attenuation in women. Other dietary intake and lifestyle
      related factors such as smoking status and physical activity had a lower effect
      on this association. Because the apolipoprotein and lipoprotein ratios share
      similar diet and lifestyle determinants as well as being highly correlated, we
      conclude that either of these ratios may be a sufficient indicator of
      dyslipidemia.

PMID- 22848406
TI  - The frames of reference of the motor-visual aftereffect.
AB  - Repeatedly performing similar motor acts produces short-term adaptive changes in
      the agent's motor system. One striking use-dependent effect is the motor-to
      visual aftereffect (MVA), a short-lasting negative bias in the conceptual
      categorization of visually-presented training-related motor behavior. The MVA is
      considered the behavioral counterpart of the adaptation of visuomotor neurons
      that code for congruent executed and observed motor acts. Here we characterize
      which features of the motor training generate the MVA, along 3 main dimensions:
      a) the relative role of motor acts vs. the semantics of the task-set; b) the role
      of muscular-specific vs. goal-specific training and c) the spatial frame of
      reference with respect to the whole body. Participants were asked to repeatedly
      push or pull some small objects in a bowl as we varied different components of
      adapting actions across three experiments. The results show that a) the semantic
      value of the instructions given to the participant have no role in generating the
      MVA, which depends only on the motor meaning of the training act; b) both
      intrinsic body movements and extrinsic action goals contribute simultaneously to
      the genesis of the MVA and c) changes in the relative position of the acting hand
      compared to the observed hand, when they do not involve changes to the movement
      performed or to the action meaning, do not have an effect on the MVA. In these
      series of experiments we confirm that recent motor experiences produce measurable
      changes in how humans see each others' actions. The MVA is an exquisite motor
      effect generated by two distinct motor sub-systems, one operating in an
      intrinsic, muscular specific, frame of reference and the other operating in an
      extrinsic motor space.

PMID- 22848408
TI  - Scheduled daily mating induces circadian anticipatory activity rhythms in the
      male rat.
AB  - Daily schedules of limited access to food, palatable high calorie snacks, water
      and salt can induce circadian rhythms of anticipatory locomotor activity in rats
      and mice. All of these stimuli are rewarding, but whether anticipation can be
      induced by neural correlates of reward independent of metabolic perturbations
      associated with manipulations of food and hydration is unclear. Three experiments
      were conducted to determine whether mating, a non-ingestive behavior that is
      potently rewarding, can induce circadian anticipatory activity rhythms in male
      rats provided scheduled daily access to steroid-primed estrous female rats. In
      Experiment 1, rats anticipated access to estrous females in the mid-light period,
      but also exhibited post-coital eating and running. In Experiment 2, post-coital
      eating and running were prevented and only a minority of rats exhibited
      anticipation. Rats allowed to see and smell estrous females showed no
      anticipation. In both experiments, all rats exhibited sustained behavioral
      arousal and multiple mounts and intromissions during every session, but
      ejaculated only every 2-3 days. In Experiment 3, the rats were given more time
      with individual females, late at night for 28 days, and then in the midday for 28
      days. Ejaculation rates increased and anticipation was robust to night sessions
      and significant although weaker to day sessions. The anticipation rhythm
      persisted during 3 days of constant dark without mating. During anticipation of
      nocturnal mating, the rats exhibited a significant preference for a tube to the
      mating cage over a tube to a locked cage with mating cage litter. This apparent
      place preference was absent during anticipation of midday mating, which may
      reflect a daily rhythm of sexual reward. The results establish mating as a reward
      stimulus capable of inducing circadian rhythms of anticipatory behavior in the
      male rat, and reveal a critical role for ejaculation, a modulatory role for time
      of day, and a potential confound role for uncontrolled food intake.

PMID- 22848409
TI  - Intergenerational predictors of birth weight in the Philippines: correlations
      with mother's and father's birth weight and test of maternal constraint.
AB  - BACKGROUND: Birth weight (BW) predicts many health outcomes, but the relative
      contributions of genes and environmental factors to BW remain uncertain. Some
      studies report stronger mother-offspring than father-offspring BW correlations,
      with attenuated father-offspring BW correlations when the mother is stunted.
      These findings have been interpreted as evidence that maternal genetic or
      environmental factors play an important role in determining birth size, with
      small maternal size constraining paternal genetic contributions to offspring BW.
      Here we evaluate mother-offspring and father-offspring birth weight (BW)
      associations and evaluate whether maternal stunting constrains genetic
      contributions to offspring birth size. METHODS/PRINCIPAL FINDINGS: Data include
      BW of offspring (n = 1,101) born to female members (n = 382) and spouses of male
      members (n = 275) of a birth cohort (born 1983-84) in Metropolitan Cebu,
      Philippines. Regression was used to relate parental and offspring BW adjusting
      for confounders. Resampling testing was used to evaluate whether false paternity
      could explain any evidence for excess matrilineal inheritance. In a pooled model
      adjusting for maternal height and confounders, parental BW was a borderline
      significantly stronger predictor of offspring BW in mothers compared to fathers
      (sex of parent interaction p = 0.068). In separate multivariate models, each kg
      in mother's and father's BW predicted a 271+/-53 g (p<0.00001) and 132+/-55 g (p
      = 0.017) increase in offspring BW, respectively. Resampling statistics suggested
      that false paternity rates of >25% and likely 50% would be needed to explain
      these differences. There was no interaction between maternal stature and maternal
      BW (interaction p = 0.520) or paternal BW (p = 0.545). CONCLUSIONS/SIGNIFICANCE:
      Each kg change in mother's BW predicted twice the change in offspring BW as
      predicted by a change in father's BW, consistent with an intergenerational
      maternal effect on offspring BW. Evidence for excess matrilineal BW heritability
      at all levels of maternal stature points to indirect genetic, mitochondrial, or
      epigenetic maternal contributions to offspring fetal growth.

PMID- 22848407
TI  - Do premenopausal women with major depression have low bone mineral density? A 36
      month prospective study.
AB  - BACKGROUND: An inverse relationship between major depressive disorder (MDD) and
      bone mineral density (BMD) has been suggested, but prospective evaluation in
      premenopausal women is lacking. METHODS: Participants of this prospective study
      were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls
      (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck,
      total hip, mid-distal radius, trochanter, and Ward's triangle, as well as serum
      intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic
      hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6,
      12, 24, and 36 months. 25-hydroxyvitamin D was measured at baseline. RESULTS: At
      baseline, BMD tended to be lower in women with MDD compared to controls and BMD
      remained stable over time in both groups. At baseline, 6, 12, and 24 months
      intact PTH levels were significantly higher in women with MDD vs. controls. At
      baseline, ionized calcium and 25-hydroxyvitamin D levels were significantly lower
      in women with MDD compared to controls. At baseline and 12 months, bone-specific
      alkaline phosphatase, a marker of bone formation, was significantly higher in
      women with MDD vs. controls. Plasma ACTH was also higher in women with MDD at
      baseline and 6 months. Serum osteocalcin, urinary N-telopeptide, serum cortisol,
      and urinary free cortisol levels were not different between the two groups
      throughout the study. CONCLUSION: Women with MDD tended to have lower BMD than
      controls over time. Larger and longer studies are necessary to extend these
      observations with the possibility of prophylactic therapy for osteoporosis. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT 00006180.

PMID- 22848410
TI  - Testing the effectiveness of an international conservation agreement: marketplace
      forensics and CITES caviar trade regulation.
AB  - BACKGROUND: The international wildlife trade is a key threat to biodiversity.
      Temporal genetic marketplace monitoring can determine if wildlife trade
      regulation efforts such as the Convention on International Trade in Endangered
      Species (CITES) are succeeding. Protected under CITES effective 1997, sturgeons
      and paddlefishes, the producers of black caviar, are flagship CITES species.
      METHODOLOGY/PRINCIPAL FINDINGS: We test whether CITES has limited the amount of
      fraudulent black caviar reaching the marketplace. Using mitochondrial DNA-based
      methods, we compare mislabeling in caviar and meat purchased in the New York City
      area pre and post CITES listing. Our recent sampling of this market reveals a
      decrease in mislabeled caviar (2006-2008; 10%; n = 90) compared to pre-CITES
      implementation (1995-1996; 19%; n = 95). Mislabeled caviar was found only in
      online purchase (n = 49 online/41 retail). CONCLUSIONS/SIGNIFICANCE: Stricter
      controls on importing and exporting as per CITES policies may be having a
      positive conservation effect by limiting the amount of fraudulent caviar reaching
      the marketplace. Sturgeons and paddlefishes remain a conservation priority,
      however, due to continued overfishing and habitat degradation. Other marine and
      aquatic species stand to benefit from the international trade regulation that can
      result from CITES listing.

PMID- 22848411
TI  - Numerous clones resistant to Phytophthora palmivora in the "Guiana" genetic group
      of Theobroma cacao L.
AB  - Cocoa black pod rot, a disease caused by Stramenopiles of the genus Phytophthora,
      and particularly by the pan-tropical species P. palmivora, causes serious
      production losses worldwide. In order to reduce the impact of these pests and
      diseases, preference is given to genetic control using resistant varieties and,
      to that end, breeders seek sources of resistance in wild cocoa trees. For
      instance, surveys of spontaneous cocoa trees in French Guiana between 1985 and
      1995 led to the collection of abundant plant material forming a particular
      genetic group (the "Guiana" group). Following numerous one-off studies
      demonstrating the merits of this group as a source of resistance to Phytophthora,
      this article presents the results of a comprehensive study assessing the
      resistance of 186 "Guiana" clones in relation to the Guianan strain (GY 27) of P.
      palmivora. This study, undertaken in French Guiana, using an efficient
      methodology (ten series of tests and a statistical test adapted to the ordinal
      nature of the data) confirmed that the "Guiana" genetic group does indeed
      constitute an important source of resistance to P. palmivora, though with some
      variations depending on the demes of origin. Numerous clones (59) proved to be as
      resistant as the SCAVINA 6 resistance control, whilst nine were statistically
      more resistant. The "Resistant" and "Moderately Resistant" Guianan clones
      totalled 108 (58% of the total tested). Some of the clones more resistant than
      SCAVINA 6 could be incorporated into numerous cocoa breeding programmes,
      particularly those that also display other notable qualities. The same applies
      for numerous other clones equivalent to SCAVINA 6, especially the "elite"' clones
      GU 134-B, GU 139-A and GU 285-A.

PMID- 22848412
TI  - Genetic markers enhance coronary risk prediction in men: the MORGAM prospective
      cohorts.
AB  - BACKGROUND: More accurate coronary heart disease (CHD) prediction, specifically
      in middle-aged men, is needed to reduce the burden of disease more effectively.
      We hypothesised that a multilocus genetic risk score could refine CHD prediction
      beyond classic risk scores and obtain more precise risk estimates using a
      prospective cohort design. METHODS: Using data from nine prospective European
      cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy
      men at baseline, and used Cox proportional hazards models to examine associations
      between CHD and risk scores based on genetic variants representing 13 genomic
      regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred.
      Genetic risk scores were validated in men with at least 10 years of follow-up
      (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two
      haplotypes, with effect estimates from previous genome-wide association studies.
      GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated
      from these prospective cohorts using 10-fold cross-validation. Scores were added
      to a model adjusted for classic risk factors comprising the Framingham risk score
      and 10-year risks were derived. RESULTS: Both scores improved net
      reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%,
      p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement
      1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases)
      improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net
      reclassification improvement remained significant for both scores when family
      history of CHD was added to the baseline model for this male subgroup improving
      prediction of early onset CHD events. CONCLUSIONS: Genetic risk scores add
      precision to risk estimates for CHD and improve prediction beyond classic risk
      factors, particularly for middle aged men.

PMID- 22848413
TI  - Heat loss may explain bill size differences between birds occupying different
      habitats.
AB  - BACKGROUND: Research on variation in bill morphology has focused on the role of
      diet. Bills have other functions, however, including a role in heat and water
      balance. The role of the bill in heat loss may be particularly important in birds
      where water is limiting. Song sparrows localized in coastal dunes and salt marsh
      edge (Melospiza melodia atlantica) are similar in size to, but have bills with a
      17% greater surface area than, those that live in mesic habitats (M. m. melodia),
      a pattern shared with other coastal sparrows. We tested the hypotheses that
      sparrows can use their bills to dissipate "dry" heat, and that heat loss from the
      bill is higher in M. m. atlantica than M. m. melodia, which would indicate a role
      of heat loss and water conservation in selection for bill size.
      METHODOLOGY/PRINCIPAL FINDINGS: Bill, tarsus, and body surface temperatures were
      measured using thermal imaging of sparrows exposed to temperatures from 15-37
      degrees C and combined with surface area and physical modeling to estimate the
      contribution of each body part to total heat loss. Song sparrow bills averaged 5
      10 degrees C hotter than ambient. The bill of M. m atlantica dissipated up to 33%
      more heat and 38% greater proportion of total heat than that of M. m. melodia.
      This could potentially reduce water loss requirements by approximately 7.7%.
      CONCLUSIONS/SIGNIFICANCE: This >30% higher heat loss in the bill of M. m.
      atlantica is independent of evaporative water loss and thus could play an
      important role in the water balance of sparrows occupying the hot and exposed
      dune/salt marsh environments during the summer. Heat loss capacity and water
      conservation could play an important role in the selection for bill size
      differences between bird populations and should be considered along with trophic
      adaptations when studying variation in bill size.

PMID- 22848414
TI  - IKAROS deletions dictate a unique gene expression signature in patients with
      adult B-cell acute lymphoblastic leukemia.
AB  - BACKGROUND: Deletions of IKAROS (IKZF1) frequently occur in B-cell precursor
      acute lymphoblastic leukemia (B-ALL) but the mechanisms by which they influence
      pathogenesis are unclear. To address this issue, a cohort of 144 adult B-ALL
      patients (106 BCR-ABL1-positive and 38 B-ALL negative for known molecular
      rearrangements) was screened for IKZF1 deletions by single nucleotide
      polymorphism (SNP) arrays; a sub-cohort of these patients (44%) was then analyzed
      for gene expression profiling. PRINCIPAL FINDINGS: Total or partial deletions of
      IKZF1 were more frequent in BCR-ABL1-positive than in BCR-ABL1-negative B-ALL
      cases (75% vs 58%, respectively, p = 0.04). Comparison of the gene expression
      signatures of patients carrying IKZF1 deletion vs those without showed a unique
      signature featured by down-regulation of B-cell lineage and DNA repair genes and
      up-regulation of genes involved in cell cycle, JAK-STAT signalling and stem cell
      self-renewal. Through chromatin immunoprecipitation and luciferase reporter
      assays we corroborated these findings both in vivo and in vitro, showing that
      Ikaros deleted isoforms lacked the ability to directly regulate a large group of
      the genes in the signature, such as IGLL1, BLK, EBF1, MSH2, BUB3, ETV6, YES1,
      CDKN1A (p21), CDKN2C (p18) and MCL1. CONCLUSIONS: Here we identified and
      validated for the first time molecular pathways specifically controlled by IKZF1,
      shedding light into IKZF1 role in B-ALL pathogenesis.

PMID- 22848415
TI  - Sickness absence following coronary revascularisation. A national study of women
      and men of working age in Sweden 1994-2006.
AB  - BACKGROUND: Evidence based and gender specific knowledge about sickness absence
      following coronary revascularisation is lacking. The objective was to investigate
      sickness absence after a first coronary artery bypass grafting (CABG) or
      percutaneous coronary intervention (PCI) among women and men in a national
      Swedish study. MATERIALS AND METHODS: All patients 30-63 years of age, who
      underwent a first CABG (n = 22,985, 16% women) or PCI (40,891, 22% women) in
      Sweden between 1994 and 2006 were included. Information on sickness absence, co
      morbidity, and other patient characteristics was obtained from national
      registers. Long-term sickness absence (LTSA) was defined as >180 and >90 sick
      leave days in the first sick-leave spell following CABG and PCI, respectively.
      Prevalence ratio (PR) and 95% confidence interval (CI) of LTSA were calculated.
      FINDINGS: LTSA followed the interventions in 41% and 36% for CABG and PCI
      patients, respectively. Women had more often LTSA compared with men, (CABG PR =
      1.23: 95% CI 1.19-1.28 and PCI PR = 1.19; 95% CI 1.16-1.23). A history of
      sickness absence the year before the intervention increased the risk for LTSA
      after the intervention in both genders. Among women, older age, or being self
      employed or unemployed was associated with a lower risk for LTSA. Among men
      previous cardiovascular disease, diabetes and low socio-economic position
      increased the risk. During the observation period, there was no change in
      sickness absence rates among PCI patients but an increase among CABG patients
      adjusting for patient characteristics. CONCLUSION: This national study covering a
      13-year period shows that long-term sickness absence following coronary
      revascularisation is common in Sweden, especially among women, and is associated
      with socio-economic position, co-morbidity, and sickness absence during the year
      before the intervention. Gender specific scientific knowledge about use and
      effects of sickness absence following coronary revascularisation is warranted for
      the patients, the treating physicians, the healthcare sector, and the society.

PMID- 22848416
TI  - Prediction of expected years of life using whole-genome markers.
AB  - Genetic factors are believed to account for 25% of the interindividual
      differences in Years of Life (YL) among humans. However, the genetic loci that
      have thus far been found to be associated with YL explain a very small proportion
      of the expected genetic variation in this trait, perhaps reflecting the
      complexity of the trait and the limitations of traditional association studies
      when applied to traits affected by a large number of small-effect genes. Using
      data from the Framingham Heart Study and statistical methods borrowed largely
      from the field of animal genetics (whole-genome prediction, WGP), we developed a
      WGP model for the study of YL and evaluated the extent to which thousands of
      genetic variants across the genome examined simultaneously can be used to predict
      interindividual differences in YL. We find that a sizable proportion of
      differences in YL--which were unexplained by age at entry, sex, smoking and BMI-
      can be accounted for and predicted using WGP methods. The contribution of genomic
      information to prediction accuracy was even higher than that of smoking and body
      mass index (BMI) combined; two predictors that are considered among the most
      important life-shortening factors. We evaluated the impacts of familial
      relationships and population structure (as described by the first two marker
      derived principal components) and concluded that in our dataset population
      structure explained partially, but not fully the gains in prediction accuracy
      obtained with WGP. Further inspection of prediction accuracies by age at death
      indicated that most of the gains in predictive ability achieved with WGP were due
      to the increased accuracy of prediction of early mortality, perhaps reflecting
      the ability of WGP to capture differences in genetic risk to deadly diseases such
      as cancer, which are most often responsible for early mortality in our sample.

PMID- 22848417
TI  - Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development
      through MITF, BCL2 and cyclin D2.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play central roles
      in diverse pathological processes. In this study, we investigated the effect of
      microRNA-182 (miR-182) on the development of posterior uveal melanomas.
      Initially, we demonstrated that miR-182 expression was dependent on p53 induction
      in uveal melanoma cells. Interestingly, transient transfection of miR-182 into
      cultured uveal melanoma cells led to a significant decrease in cell growth,
      migration, and invasiveness. Cells transfected with miR-182 demonstrated cell
      cycle G1 arrest and increased apoptotic activity. Using bioinformatics, we
      identified three potential targets of miR-182, namely MITF, BCL2 and cyclin D2.
      miR-182 was shown to have activity on mRNA expression by targeting the 3'
      untranslated region of MITF, BCL2 and cyclin D2. Subsequent Western blot analysis
      confirmed the downregulation of MITF, BCL2 and cyclin D2 protein expression. The
      expression of oncogene c-Met and its downstream Akt and ERK1/2 pathways was also
      downregulated by miR-182. Concordant with the findings that miR-182 was decreased
      in uveal melanoma tissue samples, overexpression of miR-182 also suppressed the
      in vivo growth of uveal melanoma cells. Our results demonstrated that miR-182, a
      p53 dependent miRNA, suppressed the expression of MITF, BCL2, cyclin D2 and
      functioned as a potent tumor suppressor in uveal melanoma cells.

PMID- 22848419
TI  - Cumulative cultural evolution and demography.
AB  - The idea that demographic change may spur or slow down technological change has
      become widely accepted among evolutionary archaeologists and anthropologists. Two
      models have been particularly influential in promoting this idea: a mathematical
      model by Joseph Henrich, developed to explain the Tasmanian loss of culture
      during the Holocene; and an agent-based adaptation thereof, devised by Powell et
      al. to explain the emergence of modern behaviour in the Late Pleistocene.
      However, the models in question make rather strong assumptions about the
      distribution of skills among social learners and about the selectivity of social
      learning strategies. Here I examine the behaviour of these models under more
      conservative and, on empirical and theoretical grounds, equally reasonable
      assumptions. I show that, some qualifications notwithstanding, Henrich's model
      largely withstands my robustness tests. The model of Powell et al., in contrast,
      does not--a finding that warrants a fair amount of skepticism towards Powell et
      al.'s explanation of the Upper Paleolithic transition. More generally, my
      evaluation of the accounts of Henrich and of Powell et al. helpfully clarify
      which inferences their popular models do and not support.

PMID- 22848418
TI  - Microarray analysis of the intestinal host response in Giardia duodenalis
      assemblage E infected calves.
AB  - Despite Giardia duodenalis being one of the most commonly found intestinal
      pathogens in humans and animals, little is known about the host-parasite
      interactions in its natural hosts. Therefore, the objective of this study was to
      investigate the intestinal response in calves following a G. duodenalis
      infection, using a bovine high-density oligo microarray to analyze global gene
      expression in the small intestine. The resulting microarray data suggested a
      decrease in inflammation, immune response, and immune cell migration in infected
      animals. These findings were examined in more detail by histological analyses
      combined with quantitative real-time PCR on a panel of cytokines. The
      transcription levels of IL-6, IL-8, IL-13, IL-17, and IFN-gamma showed a trend of
      being downregulated in the jejunum of infected animals compared to the negative
      controls. No immune cell recruitment could be seen after infection, and no
      intestinal pathologies, such as villus shortening or increased levels of
      apoptosis. Possible regulators of this intestinal response are the nuclear
      peroxisome proliferator-activated receptors alpha (PPARalpha), and gamma
      (PPARgamma) and the enzyme adenosine deaminase (ADA), all for which an
      upregulated expression was found in the microarray and qRT-PCR analyses.

PMID- 22848420
TI  - Upregulation of the coagulation factor VII gene during glucose deprivation is
      mediated by activating transcription factor 4.
AB  - BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes
      is necessary for hemostasis. Stressful conditions trigger adaptive cellular
      responses and delay processing of most proteins, potentially affecting plasma
      levels of proteins secreted exclusively by hepatocytes. We examined the effect of
      glucose deprivation on expression of coagulation proteins by the human hepatoma
      cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation
      factor VII, which is required for initiation of blood coagulation, was elevated
      by glucose deprivation, while expression of other coagulation proteins decreased.
      Realtime PCR and ELISA demonstrated that the relative percentage expression +/-
      SD of steady-state F7 mRNA and secreted factor VII antigen were significantly
      increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3%
      respectively, p<0.001) at 24 hr of treatment. The integrated stress response was
      induced, as indicated by upregulation of transcription factor ATF4 and of
      additional stress-responsive genes. Small interfering RNAs directed against ATF4
      potently reduced basal F7 expression, and prevented F7 upregulation by glucose
      deprivation. The response of the endogenous F7 gene was replicated in reporter
      gene assays, which further indicated that ATF4 effects were mediated via
      interaction with an amino acid response element in the F7 promoter.
      CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7
      expression in a mechanism reliant on prior ATF4 upregulation primarily due to
      increased transcription from the ATF4 gene. Of five coagulation protein genes
      examined, only F7 was upregulated, suggesting that its functions may be important
      in a systemic response to glucose deprivation stress.

PMID- 22848421
TI  - PKC-dependent human monocyte adhesion requires AMPK and Syk activation.
AB  - PKC plays a pivotal role in mediating monocyte adhesion; however, the underlying
      mechanisms of PKC-mediated cell adhesion are still unclear. In this study, we
      elucidated the signaling network of phorbol ester PMA-stimulated human monocyte
      adhesion. Our results with pharmacological inhibitors suggested the involvement
      of AMPK, Syk, Src and ERK in PKC-dependent adhesion of THP-1 monocytes to culture
      plates. Biochemical analysis further confirmed the ability of PMA to activate
      these kinases, as well as the involvement of AMPK-Syk-Src signaling in this
      event. Direct protein interaction between AMPK and Syk, which requires the kinase
      domain of AMPK and linker region of Syk, was observed following PMA stimulation.
      Notably, we identified Syk as a novel downstream target of AMPK; AICAR can induce
      Syk phosphorylation at Ser178 and activation of this kinase. However, activation
      of AMPK alone, either by stimulation with AICAR or by overexpression, is not
      sufficient to induce monocyte adhesion. Studies further demonstrated that PKC
      mediated ERK signaling independent of AMPK activation is also involved in cell
      adhesion. Moreover, AMPK, Syk, Src and ERK signaling were also required for PMA
      to induce THP-1 cell adhesion to endothelial cells as well as to induce adhesion
      response of human primary monocytes. Taken together, we propose a bifurcated
      kinase signaling pathway involved in PMA-mediated adhesion of monocytes. PKC can
      activate LKB1/AMPK, leading to phosphorylation and activation of Syk, and
      subsequent activation of Src and FAK. In addition, PKC-dependent ERK activation
      induces a coordinated signal for cytoskeleton rearrangement and cell adhesion.
      For the first time we demonstrate Syk as a novel substrate target of AMPK, and
      shed new light on the role of AMPK in monocyte adhesion, in addition to its well
      identified functions in energy homeostasis.

PMID- 22848422
TI  - Tenofovir use and renal insufficiency among pregnant and general adult population
      of HIV-infected, ART-naive individuals in Lilongwe, Malawi.
AB  - BACKGROUND: The Malawian government recently changed its prevention of mother-to
      child transmission (PMTCT) regimen and plans to change its first-line
      antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a
      fixed-dose combination tablet. Implementation could be challenging if baseline
      creatinine clearance (CrCl) screening were required to assess renal function
      prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among
      HIV-infected, ART-naive individuals. METHODOLOGY: Data on HIV-infected, ART-naive
      adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi
      were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was
      derived from the Cockroft-Gault equation. Multivariable logistic regression
      modeled the association of age, body mass index (BMI), hemoglobin, CD4 cell count
      <350 cells/mm(3), gender, and pregnancy with CrCl<50 ml/min. RESULTS: The
      analysis included 3508 patients with values for creatinine clearance. Most
      subjects were female (90.6%) with a median age of 26 years (IQR 22-29). The
      median CD4 cell count was 444 (IQR 298.0-561.0), and 85.2% percent of women in
      our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%). A BMI
      less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45-32.09)) was
      associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR
      = 0.69, 95% CI = 0.56-0.86) and non-pregnant females (OR = 0.21, 95% CI = 0.04
      0.97) was protective against CrCl<50 ml/min. DISCUSSION: Our findings indicate
      few patients would be excluded from a TDF-based antiretroviral regimen,
      suggesting baseline creatinine clearance assessment may not be necessary for
      implementation. However, in ART settings individuals with low BMI or anemia could
      potentially be at increased risk for lower CrCl.

PMID- 22848425
TI  - Toll-like signaling and the cytokine IL-6 regulate histone deacetylase dependent
      neuronal survival.
AB  - Histone deacetylase (HDAC) proteins have a role in promoting neuronal survival in
      vitro, but the mechanism underlying this function has not been identified. Here
      we provide evidence that components of the neuronal microenvironment, including
      non-neuronal cells and defined culture media, can mitigate midbrain neuronal cell
      death induced by HDAC inhibitor treatment. Using microarrays we further
      identified gene expression changes taking place in non-neuronal cells as a result
      of HDAC inhibition. This analysis demonstrated that HDAC inhibitor treatment
      results in the down-regulation of immunity related signaling factors, in
      particular the Toll-like receptors (TLR). TLR signaling is active in cultured
      midbrain cells, yet blocking TLR receptors is not sufficient to cause neuronal
      cell death. In contrast, selective activation of this pathway using TLR ligands
      can modestly block the effects of HDAC inhibition. Furthermore, we observed that
      the negative effects of HDAC inhibitor treatment on neuronal survival could be
      more substantially blocked by the cytokine Interleukin-6 (IL-6), which is a major
      downstream target of TLR signaling. These data suggest that HDACs function to
      promote neuronal survival by activating a TLR and IL-6 dependent pathway.

PMID- 22848423
TI  - A molecular switch driving inactivation in the cardiac K+ channel HERG.
AB  - K(+) channels control transmembrane action potentials by gating open or closed in
      response to external stimuli. Inactivation gating, involving a conformational
      change at the K(+) selectivity filter, has recently been recognized as a major
      K(+) channel regulatory mechanism. In the K(+) channel hERG, inactivation
      controls the length of the human cardiac action potential. Mutations impairing
      hERG inactivation cause life-threatening cardiac arrhythmia, which also occur as
      undesired side effects of drugs. In this paper, we report atomistic molecular
      dynamics simulations, complemented by mutational and electrophysiological
      studies, which suggest that the selectivity filter adopts a collapsed
      conformation in the inactivated state of hERG. The selectivity filter is gated by
      an intricate hydrogen bond network around residues S620 and N629. Mutations of
      this hydrogen bond network are shown to cause inactivation deficiency in
      electrophysiological measurements. In addition, drug-related conformational
      changes around the central cavity and pore helix provide a functional mechanism
      for newly discovered hERG activators.

PMID- 22848424
TI  - Infections with avian pathogenic and fecal Escherichia coli strains display
      similar lung histopathology and macrophage apoptosis.
AB  - The purpose of this study was to compare histopathological changes in the lungs
      of chickens infected with avian pathogenic (APEC) and avian fecal (A(fecal))
      Escherichia coli strains, and to analyze how the interaction of the bacteria with
      avian macrophages relates to the outcome of the infection. Chickens were infected
      intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non
      pathogenic A(fecal) strain, IMT5104. The pathogenicity of the strains was
      assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post
      infection (p.i.). Lungs were examined for histopathological changes at 12, 18,
      and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE),
      terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of
      apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17
      and IMT5104 did not cause systemic infections and the extents of lung
      colonization were two orders of magnitude lower than for the septicemic strains
      MT78 and IMT5155, yet all four strains caused the same extent of inflammation in
      the lungs. The inflammation was localized; there were some congested areas next
      to unaffected areas. Only the inflamed regions became labeled with anti-O2
      antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in
      the inflamed regions only, and before any necrotic foci could be seen. The TUNEL
      positive cells were very likely dying heterophils, as evidenced by the purulent
      inflammation. Some of the dying cells observed in avian lungs in situ may also be
      macrophages, since all four avian E. coli induced caspase 3/7 activation in
      monolayers of HD11 avian macrophages. In summary, both pathogenic and non
      pathogenic fecal strains of avian E. coli produce focal infections in the avian
      lung, and these are accompanied by inflammation and cell death in the infected
      areas.

PMID- 22848426
TI  - Variability of prefrontal neuronal discharges before and after training in a
      working memory task.
AB  - Variability of neural discharges can be revealing about the computations and
      network properties of neuronal populations during the performance of cognitive
      tasks. We sought to quantify neuronal variability in the prefrontal cortex of
      naive monkeys that were only required to fixate, and to examine how this measure
      was altered by learning and execution of a working memory task. We therefore
      performed analysis of a large database of recordings in the same animals, using
      the same stimuli, before and after training. Our results indicate that the Fano
      Factor, a measure of variability, differs across neurons depending on their
      functional properties both before and after learning. Fano Factor generally
      decreased after learning the task. Variability was modulated by task events and
      displayed lowest values during the stimulus presentation. Nonetheless, the
      decrease in variability after training was present even prior to the presentation
      of any stimuli, in the fixation period. The greatest decreases were observed
      comparing populations of neurons that exhibited elevated firing rate during the
      trial events. Our results offer insights on how properties of the prefrontal
      network are affected by performance of a cognitive task.

PMID- 22848427
TI  - IsoWeb: a bayesian isotope mixing model for diet analysis of the whole food web.
AB  - Quantitative description of food webs provides fundamental information for the
      understanding of population, community, and ecosystem dynamics. Recently, stable
      isotope mixing models have been widely used to quantify dietary proportions of
      different food resources to a focal consumer. Here we propose a novel mixing
      model (IsoWeb) that estimates diet proportions of all consumers in a food web
      based on stable isotope information. IsoWeb requires a topological description of
      a food web, and stable isotope signatures of all consumers and resources in the
      web. A merit of IsoWeb is that it takes into account variation in trophic
      enrichment factors among different consumer-resource links. Sensitivity analysis
      using realistic hypothetical food webs suggests that IsoWeb is applicable to a
      wide variety of food webs differing in the number of species, connectance, sample
      size, and data variability. Sensitivity analysis based on real topological webs
      showed that IsoWeb can allow for a certain level of topological uncertainty in
      target food webs, including erroneously assuming false links, omission of
      existent links and species, and trophic aggregation into trophospecies. Moreover,
      using an illustrative application to a real food web, we demonstrated that IsoWeb
      can compare the plausibility of different candidate topologies for a focal web.
      These results suggest that IsoWeb provides a powerful tool to analyze food-web
      structure from stable isotope data. We provide R and BUGS codes to aid efficient
      applications of IsoWeb.

PMID- 22848428
TI  - Structural origins for the loss of catalytic activities of bifunctional human
      LTA4H revealed through molecular dynamics simulations.
AB  - Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting
      enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a
      proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is
      a bi-functional enzyme that also exhibits aminopeptidase activity with a
      preference over arginyl tripeptides. Various mutations including E271Q, R563A,
      and K565A have completely or partially abolished both the functions of this
      enzyme. The crystal structures with these mutations have not shown any structural
      changes to address the loss of functions. Molecular dynamics simulations of LTA4
      and tripeptide complex structures with functional mutations were performed to
      investigate the structural and conformation changes that scripts the observed
      differences in catalytic functions. The observed protein-ligand hydrogen bonds
      and distances between the important catalytic components have correlated well
      with the experimental results. This study also confirms based on the structural
      observation that E271 is very important for both the functions as it holds the
      catalytic metal ion at its location for the catalysis and it also acts as N
      terminal recognition residue during peptide binding. The comparison of binding
      modes of substrates revealed the structural changes explaining the importance of
      R563 and K565 residues and the required alignment of substrate at the active
      site. The results of this study provide valuable information to be utilized in
      designing potent hLTA4H inhibitors as anti-inflammatory agents.

PMID- 22848429
TI  - Zoledronate inhibits ischemia-induced neovascularization by impairing the
      mobilization and function of endothelial progenitor cells.
AB  - BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are
      commonly used to treat postmenopausal osteoporosis and malignant osteolytic
      processes. Studies have shown that bone marrow-derived endothelial progenitor
      cells (EPCs) play a significant role in postnatal neovascularization. Whether the
      nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced
      neovascularization by modulating EPC functions remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically
      induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate
      (low-dose: 30 MUg/kg; high-dose: 100 MUg/kg). Doppler perfusion imaging
      demonstrated that the ischemic limb/normal side blood perfusion ratio was
      significantly lower in wild-type mice treated with low-dose zoledronate and in
      mice treated with high-dose zoledronate than in controls 4 weeks after ischemic
      surgery (control vs. low-dose vs. high-dose: 87+/-7% vs. *61+/-18% vs. **49+/
      17%, *p<0.01, **p<0.005 compared to control). Capillary densities were also
      significantly lower in mice treated with low-dose zoledronate and in mice treated
      with high-dose zoledronate than in control mice. Flow cytometry analysis showed
      impaired mobilization of EPC-like cells (Sca-1(+)/Flk-1(+)) after surgical
      induction of ischemia in mice treated with zoledronate but normal levels of
      mobilization in mice treated with vehicle. In addition, ischemic tissue from mice
      that received zoledronate treatment exhibited significantly lower levels of the
      active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated
      eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle.
      Results of the in vitro studies showed that incubation with zoledronate inhibited
      the viability, migration, and tube-forming capacities of EPC.
      CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced
      neovascularization by impairing EPC mobilization and angiogenic functions. These
      findings suggest that administration of zoledronate should be withheld in
      patients with ischemic events such as acute limb ischemia.

PMID- 22848430
TI  - The uncoordinated-5 homolog B receptor affects hepatic ischemia reperfusion
      injury.
AB  - Recent evidence has demonstrated additional roles for the neuronal guidance
      protein receptor UNC5B outside the nervous system. Given the fact that ischemia
      reperfusion injury (IRI) of the liver is a common source of liver dysfunction and
      the role of UNC5B during an acute inflammatory response we investigated the role
      of UNC5B on acute hepatic IRI. We report here that UNC5B(+/-) mice display
      reduced hepatic IRI and neutrophil (PMN) infiltration compared to WT controls.
      This correlated with serum levels of lactate dehydrogenase (LDH), aspartate-
      (AST) and alanine- (ALT) aminotransferase, the presence of PMN within ischemic
      hepatic tissue, and serum levels of inflammatory cytokines. Moreover, injection
      of an anti-UNC5B antibody resulted in a significant reduction of hepatic IR
      injury. This was associated with reduced parameters of liver injury (LDH, ALT,
      AST) and accumulation of PMN within the injured hepatic tissue. In conclusion our
      studies demonstrate a significant role for UNC5B in the development of hepatic
      IRI and identified UNC5B as a potential drug target to prevent liver dysfunction
      in the future.

PMID- 22848432
TI  - Micro and macro-habitat associations in saproxylic beetles: implications for
      biodiversity management.
AB  - Restoration of habitats is critically important in preventing full realization of
      the extinction debt owed as a result of anthropogenic habitat destruction.
      Although much emphasis has been placed on macrohabitats, suitable microhabitats
      are also vital for the survival of most species. The aim of this large-scale
      field experiment was to evaluate the relative importance of manipulated
      microhabitats, i.e., dead wood substrates of spruce (snags, and logs that were
      burned, inoculated with wood fungi or shaded) and macrohabitats, i.e., stand
      types (clear-cuts, mature managed forests, and forest reserves) for species
      richness, abundance and assemblage composition of all saproxylic and red-listed
      saproxylic beetles. Beetles were collected in emergence traps in 30 forest stands
      in 2001, 2003, 2004 and 2006. More individuals emerged from snags and untreated
      logs than from burned and shaded logs, but species richness did not differ among
      substrates. Assemblage composition differed among substrates for both all
      saproxylics and red-listed saproxylic species, mainly attributed to different
      assemblage composition on snags. This suggests that the practise of leaving snags
      for conservation purposes should be complemented with log supplementation. Clear
      cuts supported fewer species and different assemblages from mature managed
      forests and reserves. Neither abundance, nor species richness or assemblage
      composition differed between reserves and mature managed forests. This suggests
      that managed stands subjected to selective cutting, not clear-felling, maintain
      sufficient old growth characteristics and continuity to maintain more or less
      intact assemblages of saproxylic beetles. Thus, alternative management methods,
      e.g., continuity forestry should be considered for some of these stands to
      maintain continuity and conservation values. Furthermore, the significantly
      higher estimated abundance per ha of red-listed beetles in reserves underlines
      the importance of reserves for maintaining viable populations of rare red-listed
      species and as source areas for saproxylic species in boreal forest landscapes.

PMID- 22848431
TI  - Pax7 lineage contributions to the mammalian neural crest.
AB  - BACKGROUND: Neural crest cells are vertebrate-specific multipotent cells that
      contribute to a variety of tissues including the peripheral nervous system,
      melanocytes, and craniofacial bones and cartilage. Abnormal development of the
      neural crest is associated with several human maladies including cleft/lip
      palate, aggressive cancers such as melanoma and neuroblastoma, and rare
      syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss
      and pigment defects. We previously identified the transcription factor Pax7 as an
      early marker, and required component for neural crest development in chick
      embryos. In mammals, Pax7 is also thought to play a role in neural crest
      development, yet the precise contribution of Pax7 progenitors to the neural crest
      lineage has not been determined. METHODOLOGY/PRINCIPAL FINDINGS: Here we use
      Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in
      neural crest derivates. We find that Pax7 descendants contribute to multiple
      tissues including the cranial, cardiac and trunk neural crest, which in the
      cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the
      Pax3 lineage, is additionally detected in some non-neural crest tissues,
      including a subset of the epithelial cells in specific organs.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate a previously unappreciated
      widespread distribution of Pax7 descendants within and beyond the neural crest.
      They shed light regarding the regionally distinct phenotypes observed in Pax3 and
      Pax7 mutants, and provide a unique perspective into the potential roles of Pax7
      during disease and development.

PMID- 22848433
TI  - Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by
      kynurenic acid in adult hippocampal interneurons.
AB  - Kynurenic acid (KYNA), a classical ionotropic glutamate receptor antagonist is
      also purported to block the alpha7-subtype nicotinic acetylcholine receptor
      (alpha7* nAChR). Although many published studies cite this potential effect, few
      have studied it directly. In this study, the alpha7*-selective agonist, choline,
      was pressure-applied to interneurons in hippocampal subregions, CA1 stratum
      radiatum and hilus of acute brain hippocampal slices from adolescent to adult
      mice and adolescent rats. Stable alpha7* mediated whole-cell currents were
      measured using voltage-clamp at physiological temperatures. The effects of bath
      applied KYNA on spontaneous glutamatergic excitatory postsynaptic potentials
      (sEPSC) as well as choline-evoked alpha7* currents were determined. In mouse
      hilar interneurons, KYNA totally blocked sEPSC whole-cell currents in a rapid and
      reversible manner, but had no effect on choline-evoked alpha7* whole-cell
      currents. To determine if this lack of KYNA effect on alpha7* function was due to
      regional and/or species differences in alpha7* nAChRs, the effects of KYNA on
      choline-evoked alpha7* whole-cell currents in mouse and rat stratum radiatum
      interneurons were tested. KYNA had no effect on either mouse or rat stratum
      radiatum interneuron choline-evoked alpha7* whole-cell currents. Finally, to test
      whether the lack of effect of KYNA was due to unlikely slow kinetics of KYNA
      interactions with alpha7* nAChRs, recordings of a7*-mediated currents were made
      from slices that were prepared and stored in the presence of 1 mM KYNA (>90
      minutes exposure). Under these conditions, KYNA had no measurable effect on
      alpha7* nAChR function. The results show that despite KYNA-mediated blockade of
      glutamatergic sEPSCs, two types of hippocampal interneurons that express choline
      evoked alpha7* nAChR currents fail to show any degree of modulation by KYNA. Our
      results indicate that under our experimental conditions, which produced complete
      KYNA-mediated blockade of sEPSCs, claims of KYNA effects on choline-evoked
      alpha7* nAChR function should be made with caution.

PMID- 22848434
TI  - Fbxw7 controls angiogenesis by regulating endothelial Notch activity.
AB  - Notch signaling controls fundamental aspects of angiogenic blood vessel growth
      including the selection of sprouting tip cells, endothelial proliferation and
      arterial differentiation. The E3 ubiquitin ligase Fbxw7 is part of the SCF
      protein complex responsible for the polyubiquitination and thereby proteasomal
      degradation of substrates such as Notch, c-Myc and c-Jun. Here, we show that
      Fbxw7 is a critical regulator of angiogenesis in the mouse retina and the
      zebrafish embryonic trunk, which we attribute to its role in the degradation of
      active Notch. Growth of retinal blood vessel was impaired and the Notch ligand
      Dll4, which is also a Notch target, upregulated in inducible and endothelial cell
      specific Fbxw7(iECKO) mutant mice. The stability of the cleaved and active Notch
      intracellular domain was increased after siRNA knockdown of the E3 ligase in
      cultured human endothelial cells. Injection of fbxw7 morpholinos interfered with
      the sprouting of zebrafish intersegmental vessels (ISVs). Arguing strongly that
      Notch and not other Fbxw7 substrates are primarily responsible for these
      phenotypes, the genetic inactivation of Notch pathway components reversed the
      impaired ISV growth in the zebrafish embryo as well as sprouting and
      proliferation in the mouse retina. Our findings establish that Fbxw7 is a potent
      positive regulator of angiogenesis that limits the activity of Notch in the
      endothelium of the growing vasculature.

PMID- 22848435
TI  - Multi-criteria optimization of regulation in metabolic networks.
AB  - Determining the regulation of metabolic networks at genome scale is a hard task.
      It has been hypothesized that biochemical pathways and metabolic networks might
      have undergone an evolutionary process of optimization with respect to several
      criteria over time. In this contribution, a multi-criteria approach has been used
      to optimize parameters for the allosteric regulation of enzymes in a model of a
      metabolic substrate-cycle. This has been carried out by calculating the Pareto
      set of optimal solutions according to two objectives: the proper direction of
      flux in a metabolic cycle and the energetic cost of applying the set of
      parameters. Different Pareto fronts have been calculated for eight different
      "environments" (specific time courses of end product concentrations). For each
      resulting front the so-called knee point is identified, which can be considered a
      preferred trade-off solution. Interestingly, the optimal control parameters
      corresponding to each of these points also lead to optimal behaviour in all the
      other environments. By calculating the average of the different parameter sets
      for the knee solutions more frequently found, a final and optimal consensus set
      of parameters can be obtained, which is an indication on the existence of a
      universal regulation mechanism for this system.The implications from such a
      universal regulatory switch are discussed in the framework of large metabolic
      networks.

PMID- 22848436
TI  - Molecular and microscopic analysis of bacteria and viruses in exhaled breath
      collected using a simple impaction and condensing method.
AB  - Exhaled breath condensate (EBC) is increasingly being used as a non-invasive
      method for disease diagnosis and environmental exposure assessment. By using
      hydrophobic surface, ice, and droplet scavenging, a simple impaction and
      condensing based collection method is reported here. Human subjects were
      recruited to exhale toward the device for 1, 2, 3, and 4 min. The exhaled breath
      quickly formed into tiny droplets on the hydrophobic surface, which were
      subsequently scavenged into a 10 uL rolling deionized water droplet. The
      collected EBC was further analyzed using culturing, DNA stain, Scanning Electron
      Microscope (SEM), polymerase chain reaction (PCR) and colorimetry (VITEK 2) for
      bacteria and viruses.Experimental data revealed that bacteria and viruses in EBC
      can be rapidly collected using the method developed here, with an observed
      efficiency of 100 uL EBC within 1 min. Culturing, DNA stain, SEM, and qPCR
      methods all detected high bacterial concentrations up to 7000 CFU/m(3) in exhaled
      breath, including both viable and dead cells of various types. Sphingomonas
      paucimobilis and Kocuria variants were found dominant in EBC samples using VITEK
      2 system. SEM images revealed that most bacteria in exhaled breath are detected
      in the size range of 0.5-1.0 um, which is able to enable them to remain airborne
      for a longer time, thus presenting a risk for airborne transmission of potential
      diseases. Using qPCR, influenza A H3N2 viruses were also detected in one EBC
      sample. Different from other devices restricted solely to condensation, the
      developed method can be easily achieved both by impaction and condensation in a
      laboratory and could impact current practice of EBC collection. Nonetheless, the
      reported work is a proof-of-concept demonstration, and its performance in non
      invasive disease diagnosis such as bacterimia and virus infections needs to be
      further validated including effects of its influencing matrix.

PMID- 22848438
TI  - Insight into role of selection in the evolution of polyglutamine tracts in
      humans.
AB  - Glutamine tandem repeats are common in eukaryotic proteins. Although some studies
      have proposed that replication slippage plays an important role in shaping these
      repeats, the role of natural selection in glutamine tandem repeat evolution is
      somewhat unclear. In this study, we identified all of the glutamine tandem
      repeats containing four or more glutamines in human proteins and then estimated
      the nonsynonymous (d(N)) and synonymous (d(S)) substitution rates for the regions
      flanking the glutamine tandem repeats and the proteins containing them. The
      results indicated that most of the proteins containing polyglutamine (polyQ)
      tracts of four or more glutamines have undergone purifying selection, and that
      the purifying selection for the regions flanking the repeats is weaker.
      Additionally, we observed that the conserved repeats were under stronger
      selection constraints than the nonconserved repeats. Interestingly, we found that
      there was a higher level of purifying selection for the regions flanking the
      polyQ tracts encoded by pure CAG codons compared with those encoded by mixed
      codons. Based on our findings, we propose that selection has played a more
      important role than was previously speculated in constraining the expansion of
      polyQ tracts encoded by pure codons.

PMID- 22848437
TI  - Trace amounts of furan-2-carboxylic acids determine the quality of solid agar
      plates for bacterial culture.
AB  - BACKGROUND: Many investigators have recognised that a significant proportion of
      environmental bacteria exist in a viable but non-culturable state on agar plates,
      and some researchers have also noticed that some of such bacteria clearly recover
      their growth on matrices other than agar. However, the reason why agar is
      unsuitable for the growth of some bacteria has not been addressed.
      METHODOLOGY/PRINCIPAL FINDINGS: According to the guide of a bioassay for swarming
      inhibition, we identified 5-hydroxymethylfuran-2-carboxylic acid (5-HMFA) and
      furan-2-carboxylic acid (FA) as factors that inhibit bacterial swarming and
      likely inhibit extracellular polysaccharide production on agar. The furan-2
      carboxylic acids 5-HMFA and FA effectively inhibited the swarming and swimming of
      several environmental bacteria at concentrations of 1.8 and 2.3 ug L(-1) (13 and
      21 nmol L(-1)), respectively, which are equivalent to the concentrations of these
      compounds in 0.3% agar. On Luria-Bertani (LB) plates containing 1.0% agar that
      had been previously washed with MeOH, a mixture of 5-HMFA and FA in amounts
      equivalent to their original concentrations in the unwashed agar repressed the
      swarming of Escherichia coli K12 strain W3110, a representative swarming
      bacterium. CONCLUSIONS/SIGNIFICANCE: Agar that contains trace amounts of 5-HMFA
      and FA inhibits the proliferation of some slow-growing or difficult-to-culture
      bacteria on the plates, but it is useful for single colony isolation due to the
      ease of identification of swarmable bacteria as the non-swarmed colonies.

PMID- 22848439
TI  - Mapping MKP-3/FOXO1 interaction and evaluating the effect on gluconeogenesis.
AB  - BACKGROUND: MAP kinase phosphatase 3 (MKP-3) is known to attenuate the ERK
      signaling pathway. It has been recently demonstrated that MKP-3 is also a player
      in promoting hepatic glucose output in obese state by interacting and activating
      FOXO1. Reduction of hepatic MKP-3 expression is sufficient to reduce blood
      glucose levels in both diet-induced and genetically obese mice.
      METHODOLOGY/PRINCIPAL FINDINGS: In current study, the mechanism of MKP-3/FOXO1
      interaction and the effects on transcription of gluconeogenic gene and glucose
      output was investigated in Fao hepatoma cells by using mutated MKP-3 and FOXO1
      adenoviral constructs. The results indicate that MKP-3 phosphatase activity is
      not required for MKP-3/FOXO1 interaction but is essential for FOXO1 nuclear
      translocation and MKP-3 promoted gluconeogenesis. Compared to GFP control (1+/
      0.38), MKP-3 increased G6Pase gene expression by 242% (3.42+/-0.62) while
      inactive MKP-3 does not change G6Pase expression (0.98+/-0.17). The residues 200
      260 of MKP-3 and the residues 360-456 of FOXO1 are essential for mediating MKP
      3/FOXO1 interaction. Interestingly, ERK phosphorylation deficient but not Akt
      phosphorylation deficient FOXO1 mutant lost interaction with MKP-3. Furthermore,
      in vivo experiments showed that Akt phosphorylation resistant FOXO1 3A mutant is
      sufficient to rescue the hypoglycemia caused by MKP-3 knock down in the liver of
      lean mice (from 141+/-6.78 to 209+/-14.64 mg/dL). CONCLUSIONS/SIGNIFICANCE: 1)
      Critical residues mediating MKP-3/FOXO1 interaction have been identified; 2) ERK
      phosphorylation deficient FOXO1 mutant is as potent as Akt phosphorylation
      deficient FOXO1 mutant in activating transcription of gluconeogenic genes; 3)
      Constitutively active FOXO1 can rescue the hypoglycemic effect caused by reduced
      hepatic MKP-3 expression in vivo.

PMID- 22848440
TI  - Gallstone disease is associated with more severe liver damage in patients with
      non-alcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD)
      are both highly prevalent in the general population and associated with obesity
      and insulin resistance. We aimed to evaluate the prevalence of GD in a cross
      sectional study of NAFLD patients and to define whether the presence of GD is
      associated with diabetes and predicts more severe liver disease.
      METHODOLOGY/PRINCIPAL FINDINGS: We merged databases of four Liver Units,
      comprising 524 consecutive biopsy-proven NAFLD (373 males) observed between
      January 2003 and June 2010. GD was diagnosed in 108 (20%), and 313 cases (60%)
      were classified by liver biopsy as nonalcoholic steatohepatitis (NASH). The GD
      subgroup was characterized by a significantly higher prevalence of females,
      prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher
      BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively
      increased with advancing fibrosis and with the severity of necroinflammatory
      activity (p for trend  = 0.0001 and  = 0.01, respectively), without differences
      in the severity of steatosis. At multivariate analysis GD was associated with
      female gender (OR 1.37, 95% CI 1.04-1.8), age (OR 1.027, 95% CI1.003-1.05),
      fasting glucose (OR 1.21, 95% CI 1.10-1.33) and NASH (OR 1.40,95% CI 1.06-1.89),
      whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97
      0.99). When subjects with cirrhosis were excluded from analysis, the association
      between GD and fasting glucose, female gender, and NASH was maintained.
      CONCLUSION: Patients with NAFLD have a high prevalence of GD, which characterizes
      subjects with altered glucose regulation and more advanced liver disease.

PMID- 22848441
TI  - Evaluation of persistence of resistant variants with ultra-deep pyrosequencing in
      chronic hepatitis C patients treated with telaprevir.
AB  - BACKGROUND & AIMS: Telaprevir, a hepatitis C virus NS3/4A protease inhibitor has
      significantly improved sustained viral response rates when given in combination
      with pegylated interferon alfa-2a and ribavirin, compared with current standard
      of care in hepatitis C virus genotype 1 infected patients. In patients with a
      failed sustained response, the emergence of drug-resistant variants during
      treatment has been reported. It is unclear to what extent these variants persist
      in untreated patients. The aim of this study was to assess using ultra-deep
      pyrosequencing, whether after 4 years follow-up, the frequency of resistant
      variants is increased compared to pre-treatment frequencies following 14 days of
      telaprevir treatment. METHODS: Fifteen patients from 2 previous telaprevir phase
      1 clinical studies (VX04-950-101 and VX05-950-103) were included. These patients
      all received telaprevir monotherapy for 14 days, and 2 patients subsequently
      received standard of care. Variants at previously well-characterized NS3 protease
      positions V36, T54, R155 and A156 were assessed at baseline and after a follow-up
      of 4+/-1.2 years by ultra-deep pyrosequencing. The prevalence of resistant
      variants at follow-up was compared to baseline. RESULTS: Resistance associated
      mutations were detectable at low frequency at baseline. In general, prevalence of
      resistance mutations at follow-up was not increased compared to baseline. Only
      one patient had a small, but statistically significant, increase in the number of
      V36M and T54S variants 4 years after telaprevir-dosing. CONCLUSION: In patients
      treated for 14 days with telaprevir monotherapy, ultra-deep pyrosequencing
      indicates that long-term persistence of resistant variants is rare.

PMID- 22848442
TI  - N-carbamylglutamate enhances pregnancy outcome in rats through activation of the
      PI3K/PKB/mTOR signaling pathway.
AB  - Administration of N-carbamylglutamate (NCG), an analogue of endogenous N-acetyl
      glutamate (an activator of arginine synthesis) has been shown to enhance neonatal
      growth by increasing circulating arginine levels. However, the effect of NCG on
      pregnancy remains unknown. This study examined the effects of NCG on pregnancy
      outcome and evaluated potential mechanisms involved. Reproductive performance,
      embryo implantation, and concentration of amino acids in serum and uterine
      flushing, were determined in rats fed control or NCG supplemented diets. Ishikawa
      cells and JAR cells were used to examine the mechanism by which NCG affects
      embryo implantation. Dietary NCG supplementation increased serum levels of
      arginine, onithine, and proline, as well as uterine levels of arginine,
      glutamine, glutamate, and proline. Additionally, it stimulated LIF expression,
      and enhanced the activation of signal transduction and activator of transcription
      3 (Stat3), protein kinase B (PKB), and 70-kDa ribosomal protein S6 kinase (S6K1)
      during the periimplantation period, resulting in an increase in litter size but
      not birth weight. In uterine Ishikawa cells, LIF expression was also enhanced by
      treatment with arginine and its metabolites. In trophoblast JAR cells, treatment
      with arginine and its metabolites enhanced Stat3, PKB, and S6K1 activation and
      facilitated cellular adhesion activity. These effects were abolished by
      pretreatment with inhibitors of phosphatidylinositol 3-kinase (wortmannin) and
      mammalian target of rapamycin (rapamycin). The results demonstrate that NCG
      supplementation enhances pregnancy outcome and have important implications for
      the pregnancy outcome of mammalian species.

PMID- 22848443
TI  - Prediction and analysis of the protein interactome in Pseudomonas aeruginosa to
      enable network-based drug target selection.
AB  - Pseudomonas aeruginosa (PA) is a ubiquitous opportunistic pathogen that is
      capable of causing highly problematic, chronic infections in cystic fibrosis and
      chronic obstructive pulmonary disease patients. With the increased prevalence of
      multi-drug resistant PA, the conventional "one gene, one drug, one disease"
      paradigm is losing effectiveness. Network pharmacology, on the other hand, may
      hold the promise of discovering new drug targets to treat a variety of PA
      infections. However, given the urgent need for novel drug target discovery, a PA
      protein-protein interaction (PPI) network of high accuracy and coverage, has not
      yet been constructed. In this study, we predicted a genome-scale PPI network of
      PA by integrating various genomic features of PA proteins/genes by a machine
      learning-based approach. A total of 54,107 interactions covering 4,181 proteins
      in PA were predicted. A high-confidence network combining predicted high
      confidence interactions, a reference set and verified interactions that consist
      of 3,343 proteins and 19,416 potential interactions was further assembled and
      analyzed. The predicted interactome network from this study is the first large
      scale PPI network in PA with significant coverage and high accuracy. Subsequent
      analysis, including validations based on existing small-scale PPI data and the
      network structure comparison with other model organisms, shows the validity of
      the predicted PPI network. Potential drug targets were identified and prioritized
      based on their essentiality and topological importance in the high-confidence
      network. Host-pathogen protein interactions between human and PA were further
      extracted and analyzed. In addition, case studies were performed on protein
      interactions regarding anti-sigma factor MucA, negative periplasmic alginate
      regulator MucB, and the transcriptional regulator RhlR. A web server to access
      the predicted PPI dataset is available at http://research.cchmc.org/PPIdatabase/.

PMID- 22848444
TI  - Mycobacterium tuberculosis infection interferes with HIV vaccination in mice.
AB  - Tuberculosis (TB) has emerged as the most prominent bacterial disease found in
      human immunodeficiency virus (HIV)-positive individuals worldwide. Due to high
      prevalence of asymptomatic Mycobacterium tuberculosis (Mtb) infections, the
      future HIV vaccine in areas highly endemic for TB will often be administrated to
      individuals with an ongoing Mtb infection. The impact of concurrent Mtb infection
      on the immunogenicity of a HIV vaccine candidate, MultiHIV DNA/protein, was
      investigated in mice. We found that, depending on the vaccination route, mice
      infected with Mtb before the administration of the HIV vaccine showed impairment
      in both the magnitude and the quality of antibody and T cell responses to the
      vaccine components p24Gag and gp160Env. Mice infected with Mtb prior to
      intranasal HIV vaccination exhibited reduced p24Gag-specific serum IgG and IgA,
      and suppressed gp160Env-specific serum IgG as compared to respective titers in
      uninfected HIV-vaccinated controls. Importantly, in Mtb-infected mice that were
      HIV-vaccinated by the intramuscular route the virus neutralizing activity in
      serum was significantly decreased, relative to uninfected counterparts. In
      addition mice concurrently infected with Mtb had fewer p24Gag-specific IFN-gamma
      expressing T cells and multifunctional T cells in their spleens. These results
      suggest that Mtb infection might interfere with the outcome of prospective HIV
      vaccination in humans.

PMID- 22848445
TI  - High prevalence of anti-HCV antibodies in two metropolitan emergency departments
      in Germany: a prospective screening analysis of 28,809 patients.
AB  - BACKGROUND AND AIMS: The prevalence of hepatitis C virus (HCV) antibodies in
      Germany has been estimated to be in the range of 0.4-0.63%. Screening for HCV is
      recommended in patients with elevated ALT levels or significant risk factors for
      HCV transmission only. However, 15-30% of patients report no risk factors and ALT
      levels can be normal in up to 20-30% of patients with chronic HCV infection. The
      aim of this study was to assess the HCV seroprevalence in patients visiting two
      tertiary care emergency departments in Berlin and Frankfurt, respectively.
      METHODS: Between May 2008 and March 2010, a total of 28,809 consecutive patients
      were screened for the presence of anti-HCV antibodies. Anti-HCV positive sera
      were subsequently tested for HCV-RNA. RESULTS: The overall HCV seroprevalence was
      2.6% (95% CI: 2.4-2.8; 2.4% in Berlin and 3.5% in Frankfurt). HCV-RNA was
      detectable in 68% of anti-HCV positive cases. Thus, the prevalence of chronic HCV
      infection in the overall study population was 1.6% (95% CI 1.5-1.8). The most
      commonly reported risk factor was former/current injection drug use (IDU; 31.2%)
      and those with IDU as the main risk factor were significantly younger than
      patients without IDU (p<0.001) and the male-to-female ratio was 72% (121 vs. 46
      patients; p<0.001). Finally, 18.8% of contacted HCV-RNA positive patients had not
      been diagnosed previously. CONCLUSIONS: The HCV seroprevalence was more than four
      times higher compared to current estimates and almost one fifth of contacted HCV
      RNA positive patients had not been diagnosed previously.

PMID- 22848446
TI  - Persistence, spatial distribution and implications for progression detection of
      blind parts of the visual field in glaucoma: a clinical cohort study.
AB  - BACKGROUND: Visual field testing is an essential part of glaucoma care. It is
      hampered by variability related to the disease itself, response errors and
      fatigue. In glaucoma, blind parts of the visual field contribute to the diagnosis
      but--once established--not to progression detection; they only increase testing
      time. The aims of this study were to describe the persistence and spatial
      distribution of blind test locations in standard automated perimetry in glaucoma
      and to explore how the omission of presumed blind test locations would affect
      progression detection. METHODOLOGY/PRINCIPAL FINDINGS: Data from 221 eyes of 221
      patients from a cohort study with the Humphrey Field Analyzer with 30-2 grid were
      used. Patients were stratified according to baseline mean deviation (MD) in six
      strata of 5 dB width each. For one, two, three and four consecutive <0 dB
      sensitivities in the same test location in a series of baseline tests, the median
      probabilities to observe <0 dB again in the concerning test location in a follow
      up test were 76, 86, 88 and 90%, respectively. For <10 dB, the probabilities were
      88, 95, 97 and 98%, respectively. Median (interquartile range) percentages of
      test locations with three consecutive <0 dB sensitivities were 0(0-0), 0(0-2),
      4(0-9), 17(8-27), 27(20-40) and 60(50-70)% for the six MD strata. Similar
      percentages were found for a subset of test locations within 10 degree
      eccentricity (P>0.1 for all strata). Omitting test locations with three
      consecutive <0 dB sensitivities at baseline did not affect the performance of the
      MD-based Nonparametric Progression Analysis progression detection algorithm.
      CONCLUSIONS/SIGNIFICANCE: Test locations that have been shown to be reproducibly
      blind tend to display a reasonable blindness persistence and do no longer
      contribute to progression detection. There is no clinically useful universal MD
      cut-off value beyond which testing can be limited to 10 degree eccentricity.

PMID- 22848447
TI  - Rainforest pharmacopeia in Madagascar provides high value for current local and
      prospective global uses.
AB  - Botanical diversity provides value to humans through carbon sequestration, air
      and water purification, and the provisioning of wild foods and ethnomedicines.
      Here we calculate the value of botanical ethnomedicines in a rainforest region of
      Madagascar, the Makira Protected Area, using a substitution method that combines
      replacement costs and choice modeling. The Makira watershed may comprise
      approximately 0.8% of global botanical diversity and possesses enormous value
      both in its ability to provision botanical ethnomedicines to local people and as
      a source of potentially novel pharmaceutical drugs for society as a whole.
      Approximately 241 locally-recognized species are used as ethnomedicines,
      including 113 agricultural or weed species. We equated each ethnomedicinal
      treatment to the monetary value of a comparable pharmaceutical treatment adjusted
      by personal preferences in perceived efficacy (rather than from known or assumed
      medicinal equivalency). The benefit value of these botanical ethnomedicines per
      individual is $5.40-7.90 per year when using the value of highly subsidized
      Malagasy pharmaceuticals and $100.60-287.40 when using the value of American
      pharmaceuticals. Using local pharmaceuticals as substitutes, the value per
      household is $30.24-44.30 per year, equivalent to 43-63% of median annual
      household income, demonstrating their local importance. Using the value of
      American pharmaceuticals, the amount is equivalent to 22-63% of the median annual
      health care expenditures for American adults under 45 in 2006. The potential for
      developing novel biomedicines from the Makira watershed's unique flora ranges in
      untapped benefit value from $0.3-5.7 billion for American pharmaceutical
      companies, non-inclusive of the importance of providing novel medicines and
      improved healthcare to society. This study provides evidence of the tremendous
      current local and prospective global value of botanical ethnomedicines and
      furthers arguments for the conservation of tropical forests for sustainable use.

PMID- 22848448
TI  - Genetic transformation and analysis of rice OsAPx2 gene in Medicago sativa.
AB  - The OsAPx2 gene from rice was cloned to produce PBI121::OsAPx2 dual-expression
      plants, of which expression level would be increasing under stressful conditions.
      The enzyme ascorbate peroxidase (APX) in the leaves and roots of the plants
      increased with increasing exposure time to different sodium chloride (NaCl) and
      hydrogen peroxide (H(2)O(2))concentrations, as indicated by protein gel blot
      analysis. The increased enzyme yield improved the ability of the plants to resist
      the stress treatments. The OsAPx2 gene was localized in the cytoplasm of
      epidermal onion cells as indicated by the instantaneous expression of green
      fluorescence. An 80% regeneration rate was observed in Medicago sativa L. plants
      transformed with the OsAPx2 gene using Agrobacterium tumefaciens, as indicated by
      specific primer PCR. The OsAPx2 gene was expressed at the mRNA level and the
      individual M. sativa (T#1,T#2,T#5) were obtained through assaying the generation
      of positive T2 using RNA gel blot analysis. When the seeds of the wild type (WT)
      and the T2 (T#1,T#5) were incubated in culture containing MS with NaCl for 7
      days, the results as shown of following: the root length of transgenic plant was
      longer than WT plants, the H(2)O(2) content in roots of WT was more than of
      transgenic plants, the APX activity under stresses increased by 2.89 times
      compared with the WT, the malondialdehyde (MDA) content of the WT was higher than
      the transgenic plants, the leaves of the WT turned yellow, but those of the
      transgenic plants remained green and remained healthy. The chlorophyll content in
      the WT leaves was less than in the transgenic plants, after soaking in solutions
      of H(2)O(2), sodium sulfite (Na(2)SO(3)), and sodium bicarbonate (NaHCO(3)).
      Therefore, the OsAPx2 gene overexpression in transgenic M. sativa improves the
      removal of H(2)O(2) and the salt-resistance compared with WT plants. A novel
      strain of M. sativa carrying a salt-resistance gene was obtained.

PMID- 22848449
TI  - NEMO inhibits programmed necrosis in an NFkappaB-independent manner by
      restraining RIP1.
AB  - TNF can trigger two opposing responses: cell survival and cell death. TNFR1
      activates caspases that orchestrate apoptosis but some cell types switch to a
      necrotic death when treated with caspase inhibitors. Several genes that are
      required to orchestrate cell death by programmed necrosis have been identified,
      such as the kinase RIP1, but very little is known about the inhibitory signals
      that keep this necrotic cell death pathway in check. We demonstrate that T cells
      lacking the regulatory subunit of IKK, NFkappaB essential modifier (NEMO), are
      hypersensitive to programmed necrosis when stimulated with TNF in the presence of
      caspase inhibitors. Surprisingly, this pro-survival activity of NEMO is
      independent of NFkappaB-mediated gene transcription. Instead, NEMO inhibits
      necrosis by binding to ubiquitinated RIP1 to restrain RIP1 from engaging the
      necrotic death pathway. In the absence of NEMO, or if ubiquitination of RIP1 is
      blocked, necrosis ensues when caspases are blocked. These results indicate that
      recruitment of NEMO to ubiquitinated RIP1 is a key step in the TNFR1 signaling
      pathway that determines whether RIP1 triggers a necrotic death response.

PMID- 22848450
TI  - Detecting the immune system response of a 500 year-old Inca mummy.
AB  - Disease detection in historical samples currently relies on DNA extraction and
      amplification, or immunoassays. These techniques only establish pathogen presence
      rather than active disease. We report the first use of shotgun proteomics to
      detect the protein expression profile of buccal swabs and cloth samples from two
      500-year-old Andean mummies. The profile of one of the mummies is consistent with
      immune system response to severe pulmonary bacterial infection at the time of
      death. Presence of a probably pathogenic Mycobacterium sp. in one buccal swab was
      confirmed by DNA amplification, sequencing, and phylogenetic analyses. Our study
      provides positive evidence of active pathogenic infection in an ancient sample
      for the first time. The protocol introduced here is less susceptible to
      contamination than DNA-based or immunoassay-based studies. In scarce forensic
      samples, shotgun proteomics narrows the range of pathogens to detect using DNA
      assays, reducing cost. This analytical technique can be broadly applied for
      detecting infection in ancient samples to answer questions on the historical
      ecology of specific pathogens, as well as in medico-legal cases when active
      pathogenic infection is suspected.

PMID- 22848451
TI  - Rapid identification of ESKAPE bacterial strains using an autonomous microfluidic
      device.
AB  - This article describes Bacteria ID Chips ('BacChips'): an inexpensive, portable,
      and autonomous microfluidic platform for identifying pathogenic strains of
      bacteria. BacChips consist of a set of microchambers and channels molded in the
      elastomeric polymer, poly(dimethylsiloxane) (PDMS). Each microchamber is
      preloaded with mono-, di-, or trisaccharides and dried. Pressing the layer of
      PDMS into contact with a glass coverslip forms the device; the footprint of the
      device in this article is ~6 cm(2). After assembly, BacChips are degased under
      large negative pressure and are stored in vacuum-sealed plastic bags. To use the
      device, the bag is opened, a sample containing bacteria is introduced at the
      inlet of the device, and the degased PDMS draws the sample into the central
      channel and chambers. After the liquid at the inlet is consumed, air is drawn
      into the BacChip via the inlet and provides a physical barrier that separates the
      liquid samples in adjacent microchambers. A pH indicator is admixed with the
      samples prior to their loading, enabling the metabolism of the dissolved
      saccharides in the microchambers to be visualized. Importantly, BacChips operate
      without external equipment or instruments. By visually detecting the growth of
      bacteria using ambient light after ~4 h, we demonstrate that BacChips with ten
      microchambers containing different saccharides can reproducibly detect the ESKAPE
      panel of pathogens, including strains of: Enterococcus faecalis, Enteroccocus
      faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,
      Pseudomonas aeruginosa, Enterobacter aerogenes, and Enterobacter cloacae. This
      article describes a BacChip for point-of-care detection of ESKAPE pathogens and a
      starting point for designing multiplexed assays that identify bacterial strains
      from clinical samples and simultaneously determine their susceptibility to
      antibiotics.

PMID- 22848452
TI  - Validation of exposure visualization and audible distance emission for navigated
      temporal bone drilling in phantoms.
AB  - BACKGROUND: A neuronavigation interface with extended function as compared with
      current systems was developed to aid during temporal bone surgery. The interface,
      named EVADE, updates the prior anatomical image and visualizes the bone drilling
      process virtually in real-time without need for intra-operative imaging.
      Furthermore, EVADE continuously calculates the distance from the drill tip to
      segmented temporal bone critical structures (e.g. the sigmoid sinus and facial
      nerve) and produces audiovisual warnings if the surgeon drills in too close
      vicinity. The aim of this study was to evaluate the accuracy and surgical utility
      of EVADE in physical phantoms. METHODOLOGY/PRINCIPAL FINDINGS: We performed 228
      measurements assessing the position accuracy of tracking a navigated drill in the
      operating theatre. A mean target registration error of 1.33+/-0.61 mm with a
      maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal
      bone phantoms, once using EVADE, and once using a standard neuronavigation
      interface. While using standard neuronavigation the surgeons damaged three
      modeled temporal bone critical structures. No structure was hit by surgeons
      utilizing EVADE. Surgeons felt better orientated and thought they had improved
      tumor exposure with EVADE. Furthermore, we compared the distances between surface
      meshes of the virtual drill cavities created by EVADE to actual drill cavities:
      average maximum errors of 2.54+/-0.49 mm and -2.70+/-0.48 mm were found.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate that EVADE gives accurate
      feedback which reduces risks of harming modeled critical structures compared to a
      standard neuronavigation interface during temporal bone phantom drilling.

PMID- 22848453
TI  - Functional anatomy of the masking level difference, an fMRI study.
AB  - INTRODUCTION: Masking level differences (MLDs) are differences in the hearing
      threshold for the detection of a signal presented in a noise background, where
      either the phase of the signal or noise is reversed between ears. We use N0/Npi
      to denote noise presented in-phase/out-of-phase between ears and S0/Spi to denote
      a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the
      noise/signal combinations N0Spi and NpiS0 is typically 10-20 dB better than for
      N0S0. All combinations have the same spectrum, level, and duration of both the
      signal and the noise. METHODS: Ten participants (5 female), age: 22-43, with
      N0Spi-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI
      sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400
      600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle)
      were used to create the stimuli. Brain maps of statistically significant regions
      were formed from a second-level analysis using SPM5. RESULTS: The contrast NpiS0-
      N0Spi had significant regions of activation in the right pulvinar, corpus
      callosum, and insula bilaterally. The left inferior frontal gyrus had significant
      activation for contrasts N0Spi-N0S0 and NpiS0-N0S0. The contrast N0S0-N0Spi
      revealed a region in the right insula, and the contrast N0S0-NpiS0 had a region
      of significance in the left insula. CONCLUSION: Our results extend the view that
      the thalamus acts as a gating mechanism to enable dichotic listening, and suggest
      that MLD processing is accomplished through thalamic communication with the
      insula, which communicate across the corpus callosum to either enhance or
      diminish the binaural signal (depending on the MLD condition). The audibility
      improvement of the signal with both MLD conditions is likely reflected by
      activation in the left inferior frontal gyrus, a late stage in the what/where
      model of auditory processing.

PMID- 22848454
TI  - Alternative splicing of the N-terminal cytosolic and transmembrane domains of
      P2X7 controls gating of the ion channel by ADP-ribosylation.
AB  - P2X7 is a homotrimeric ion channel with two transmembrane domains and a large
      extracellular ATP-binding domain. It plays a key role in the response of immune
      cells to danger signals released from cells at sites of inflammation. Gating of
      murine P2X7 can be induced by the soluble ligand ATP, as well as by NAD(+)
      dependent ADP-ribosylation of arginine 125, a posttranslational protein
      modification catalyzed by the toxin-related ecto-enzymes ART2.1 and ART2.2. R125
      is located at the edge of the ligand-binding crevice. Recently, an alternative
      splice variant of P2X7, designated P2X7(k), was discovered that differs from the
      previously described variant P2X7(a) in the N-terminal 42 amino acid residues
      composing the first cytosolic domain and most of the Tm1 domain. Here we compare
      the two splice variants of murine P2X7 with respect to their sensitivities to
      gating by ADP-ribosylation in transfected HEK cells. Our results show that the
      P2X7(k) variant is sensitive to activation by ADP-ribosylation whereas the
      P2X7(a) variant is insensitive, despite higher cell surface expression levels.
      Interestingly, a single point mutation (R276K) renders the P2X7(a) variant
      sensitive to activation by ADP-ribosylation. Residue 276 is located at the
      interface of neighboring subunits approximately halfway between the ADP
      ribosylation site and the transmembrane domains. Moreover, we show that naive and
      regulatory T cells preferentially express the more sensitive P2X7(k) variant,
      while macrophages preferentially express the P2X7(a) variant. Our results
      indicate that differential splicing of alternative exons encoding the N-terminal
      cytosolic and transmembrane domains of P2X7 control the sensitivity of different
      immune cells to extracellular NAD(+) and ATP.

PMID- 22848455
TI  - Assemblage of a semi-arid annual plant community: abiotic and biotic filters act
      hierarchically.
AB  - The study of species coexistence and community assembly has been a hot topic in
      ecology for decades. Disentangling the hierarchical role of abiotic and biotic
      filters is crucial to understand community assembly processes. The most critical
      environmental factor in semi-arid environments is known to be water availability,
      and perennials are usually described as nurses that create milder local
      conditions and expand the niche range of several species. We aimed to broaden
      this view by jointly evaluating how biological soil crusts (BSCs), water
      availability, perennial species (presence/absence of Stipa tenacissima) and plant
      plant interactions shape a semi-arid annual plant community. The presence and
      cover of annual species was monitored during three years of contrasting climate.
      Water stress acted as the primary filter determining the species pool available
      for plant community assembly. Stipa and BSCs acted as secondary filters by
      modulating the effects of water availability. At extremely harsh environmental
      conditions, Stipa exerted a negative effect on the annual plant community, while
      at more benign conditions it increased annual community richness. Biological soil
      crusts exerted a contradictory effect depending on climate and on the presence of
      Stipa, favoring annuals in the most adverse conditions but showing repulsion at
      higher water availability conditions. Finally, interactions among co-occurring
      annuals shaped species richness and diversity of the final annual plant assembly.
      This study sheds light on the processes determining the assembly of annual
      communities and highlights the importance of Biological Soil Crusts and of
      interactions among annual plants on the final outcome of the species assembly.

PMID- 22848456
TI  - Neurogranin targets calmodulin and lowers the threshold for the induction of long
      term potentiation.
AB  - Calcium entry and the subsequent activation of CaMKII trigger synaptic plasticity
      in many brain regions. The induction of long-term potentiation (LTP) in the CA1
      region of the hippocampus requires a relatively high amount of calcium
      calmodulin. This requirement is usually explained, based on in vitro and
      theoretical studies, by the low affinity of CaMKII for calmodulin. An untested
      hypothesis, however, is that calmodulin is not randomly distributed within the
      spine and its targeting within the spine regulates LTP. We have previously shown
      that overexpression of neurogranin enhances synaptic strength in a calmodulin
      dependent manner. Here, using post-embedding immunogold labeling, we show that
      calmodulin is not randomly distributed, but spatially organized in the spine.
      Moreover, neurogranin regulates calmodulin distribution such that its
      overexpression concentrates calmodulin closer to the plasma membrane, where a
      high level of CaMKII immunogold labeling is also found. Interestingly, the
      targeting of calmodulin by neurogranin results in lowering the threshold for LTP
      induction. These findings highlight the significance of calmodulin targeting
      within the spine in synaptic plasticity.

PMID- 22848457
TI  - Trypanosoma cruzi IV causing outbreaks of acute Chagas disease and infections by
      different haplotypes in the Western Brazilian Amazonia.
AB  - BACKGROUND: Chagas disease is an emergent tropical disease in the Brazilian
      Amazon Region, with an increasing number of cases in recent decades. In this
      region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a
      reservoir of parasites that might be associated with specific molecular,
      epidemiological and clinical traits, has been little explored. The objective of
      this work is to genetically characterize stocks of T. cruzi from human cases,
      triatomines and reservoir mammals in the State of Amazonas, in the Western
      Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 96 T. cruzi samples
      from four municipalities in distant locations of the State of Amazonas. Molecular
      characterization of isolated parasites from cultures in LIT medium or directly
      from vectors or whole human blood was performed by PCR of the non-transcribed
      spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and
      sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene, and
      by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites
      from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks
      was triggered by several haplotypes of the same DTU. TcIV also occurred in
      isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and
      nuclear phylogenies is likely to be indicative of historical genetic exchange
      events resulting in mitochondrial introgression between TcIII and TcIV DTUs from
      Western Brazilian Amazon. TcI predominated among triatomines and was the unique
      DTU infecting marsupials. CONCLUSION/SIGNIFICANCE: DTU TcIV, rarely associated
      with human Chagas disease in other areas of the Amazon basin, is the major strain
      responsible for the human infections in the Western Brazilian Amazon, occurring
      in outbreaks as single or mixed infections by different haplotypes.

PMID- 22848458
TI  - The "most wanted" taxa from the human microbiome for whole genome sequencing.
AB  - The goal of the Human Microbiome Project (HMP) is to generate a comprehensive
      catalog of human-associated microorganisms including reference genomes
      representing the most common species. Toward this goal, the HMP has characterized
      the microbial communities at 18 body habitats in a cohort of over 200 healthy
      volunteers using 16S rRNA gene (16S) sequencing and has generated nearly 1,000
      reference genomes from human-associated microorganisms. To determine how well
      current reference genome collections capture the diversity observed among the
      healthy microbiome and to guide isolation and future sequencing of microbiome
      members, we compared the HMP's 16S data sets to several reference 16S collections
      to create a 'most wanted' list of taxa for sequencing. Our analysis revealed that
      the diversity of commonly occurring taxa within the HMP cohort microbiome is
      relatively modest, few novel taxa are represented by these OTUs and many common
      taxa among HMP volunteers recur across different populations of healthy humans.
      Taken together, these results suggest that it should be possible to perform whole
      genome sequencing on a large fraction of the human microbiome, including the
      'most wanted', and that these sequences should serve to support microbiome
      studies across multiple cohorts. Also, in stark contrast to other taxa, the 'most
      wanted' organisms are poorly represented among culture collections suggesting
      that novel culture- and single-cell-based methods will be required to isolate
      these organisms for sequencing.

PMID- 22848459
TI  - Atomic-level structure characterization of an ultrafast folding mini-protein
      denatured state.
AB  - Atomic-level analyses of non-native protein ensembles constitute an important
      aspect of protein folding studies to reach a more complete understanding of how
      proteins attain their native form exhibiting biological activity. Previously,
      formation of hydrophobic clusters in the 6 M urea-denatured state of an ultrafast
      folding mini-protein known as TC5b from both photo-CIDNP NOE transfer studies and
      FCS measurements was observed. Here, we elucidate the structural properties of
      this mini-protein denatured in 6 M urea performing (15)N NMR relaxation studies
      together with a thorough NOE analysis. Even though our results demonstrate that
      no elements of secondary structure persist in the denatured state, the
      heterogeneous distribution of R(2) rate constants together with observing
      pronounced heteronuclear NOEs along the peptide backbone reveals specific regions
      of urea-denatured TC5b exhibiting a high degree of structural rigidity more
      frequently observed for native proteins. The data are complemented with studies
      on two TC5b point mutants to verify the importance of hydrophobic interactions
      for fast folding. Our results corroborate earlier findings of a hydrophobic
      cluster present in urea-denatured TC5b comprising both native and non-native
      contacts underscoring their importance for ultra rapid folding. The data assist
      in finding ways of interpreting the effects of pre-existing native and/or non
      native interactions on the ultrafast folding of proteins; a fact, which might
      have to be considered when defining the starting conditions for molecular
      dynamics simulation studies of protein folding.

PMID- 22848460
TI  - Genome-wide characterization of genetic variation in the unicellular, green alga
      Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii is a model system for studying cilia, photosynthesis,
      and other core features of eukaryotes, and is also an emerging source of
      biofuels. Despite its importance to basic and applied biological research, the
      level and pattern of genetic variation in this haploid green alga has yet to be
      characterized on a genome-wide scale. To improve understanding of C.
      reinhardtii's genetic variability, we generated low coverage whole genome
      resequencing data for nearly all of the available isolates of this species, which
      were sampled from a number of sites in North America over the past ~70 years.
      Based on the analysis of more than 62,000 single nucleotide polymorphisms, we
      identified two groups of isolates that represent geographical subpopulations of
      the species. We also found that measurements of genetic diversity were highly
      variable throughout the genome, in part due to technical factors. We studied the
      level and pattern of linkage disequilibrium (LD), and observed one chromosome
      that exhibits elevated LD. Furthermore, we detected widespread evidence of
      recombination across the genome, which implies that outcrossing occurs in natural
      populations of this species. In summary, our study provides multiple insights
      into the sequence diversity of C. reinhardtii that will be useful to future
      studies of natural genetic variation in this organism.

PMID- 22848461
TI  - Asian dust storm elevates children's respiratory health risks: a spatiotemporal
      analysis of children's clinic visits across Taipei (Taiwan).
AB  - Concerns have been raised about the adverse impact of Asian dust storms (ADS) on
      human health; however, few studies have examined the effect of these events on
      children's health. Using databases from the Taiwan National Health Insurance and
      Taiwan Environmental Protection Agency, this study investigates the documented
      daily visits of children to respiratory clinics during and after ADS that
      occurred from 1997 to 2007 among 12 districts across Taipei City by applying a
      Bayesian structural additive regressive model controlled for spatial and temporal
      patterns. This study finds that the significantly impact of elevated children's
      respiratory clinic visits happened after ADS. Five of the seven lagged days had
      increasing percentages of relative rate, which was consecutively elevated from a
      2-day to a 5-day lag by 0.63%~2.19% for preschool children (i.e., 0~6 years of
      age) and 0.72%~3.17% for school children (i.e., 7~14 years of age). The spatial
      pattern of clinic visits indicated that geographical heterogeneity was possibly
      associated with the clinic's location and accessibility. Moreover, day-of-week
      effects were elevated on Monday, Friday, and Saturday. We concluded that ADS may
      significantly increase the risks of respiratory diseases consecutively in the
      week after exposure, especially in school children.

PMID- 22848463
TI  - The redder the better: wing color predicts flight performance in monarch
      butterflies.
AB  - The distinctive orange and black wings of monarchs (Danaus plexippus) have long
      been known to advertise their bitter taste and toxicity to potential predators.
      Recent work also showed that both the orange and black coloration of this species
      can vary in response to individual-level and environmental factors. Here we
      examine the relationship between wing color and flight performance in captive
      reared monarchs using a tethered flight mill apparatus to quantify butterfly
      flight speed, duration and distance. In three different experiments (totaling 121
      individuals) we used image analysis to measure body size and four wing traits
      among newly-emerged butterflies prior to flight trials: wing area, aspect ratio
      (length/width), melanism, and orange hue. Results showed that monarchs with
      darker orange (approaching red) wings flew longer distances than those with
      lighter orange wings in analyses that controlled for sex and other morphometric
      traits. This finding is consistent with past work showing that among wild
      monarchs, those sampled during the fall migration are darker in hue (redder) than
      non-migratory monarchs. Together, these results suggest that pigment deposition
      onto wing scales during metamorphosis could be linked with traits that influence
      flight, such as thorax muscle size, energy storage or metabolism. Our results
      reinforce an association between wing color and flight performance in insects
      that is suggested by past studies of wing melansim and seasonal polyphenism, and
      provide an important starting point for work focused on mechanistic links between
      insect movement and color.

PMID- 22848462
TI  - Scale-free behaviour of amino acid pair interactions in folded proteins.
AB  - The protein structure is a cumulative result of interactions between amino acid
      residues interacting with each other through space and/or chemical bonds. Despite
      the large number of high resolution protein structures, the "protein structure
      code" has not been fully identified. Our manuscript presents a novel approach to
      protein structure analysis in order to identify rules for spatial packing of
      amino acid pairs in proteins. We have investigated 8706 high resolution non
      redundant protein chains and quantified amino acid pair interactions in terms of
      solvent accessibility, spatial and sequence distance, secondary structure, and
      sequence length. The number of pairs found in a particular environment is stored
      in a cell in an 8 dimensional data tensor. When plotting the cell population
      against the number of cells that have the same population size, a scale free
      organization is found. When analyzing which amino acid paired residues
      contributed to the cells with a population above 50, pairs of Ala, Ile, Leu and
      Val dominate the results. This result is statistically highly significant. We
      postulate that such pairs form "structural stability points" in the protein
      structure. Our data shows that they are in buried alpha-helices or beta-strands,
      in a spatial distance of 3.8-4.3A and in a sequence distance >4 residues. We
      speculate that the scale free organization of the amino acid pair interactions in
      the 8D protein structure combined with the clear dominance of pairs of Ala, Ile,
      Leu and Val is important for understanding the very nature of the protein
      structure formation. Our observations suggest that protein structures should be
      considered as having a higher dimensional organization.

PMID- 22848464
TI  - Adaptation in sound localization processing induced by interaural time difference
      in amplitude envelope at high frequencies.
AB  - BACKGROUND: When a second sound follows a long first sound, its location appears
      to be perceived away from the first one (the localization/lateralization
      aftereffect). This aftereffect has often been considered to reflect an efficient
      neural coding of sound locations in the auditory system. To understand
      determinants of the localization aftereffect, the current study examined whether
      it is induced by an interaural temporal difference (ITD) in the amplitude
      envelope of high frequency transposed tones (over 2 kHz), which is known to
      function as a sound localization cue. METHODOLOGY/PRINCIPAL FINDINGS: In
      Experiment 1, participants were required to adjust the position of a pointer to
      the perceived location of test stimuli before and after adaptation. Test and
      adapter stimuli were amplitude modulated (AM) sounds presented at high
      frequencies and their positional differences were manipulated solely by the
      envelope ITD. Results showed that the adapter's ITD systematically affected the
      perceived position of test sounds to the directions expected from the
      localization/lateralization aftereffect when the adapter was presented at +/-600
      us ITD; a corresponding significant effect was not observed for a 0 us ITD
      adapter. In Experiment 2, the observed adapter effect was confirmed using a
      forced-choice task. It was also found that adaptation to the AM sounds at high
      frequencies did not significantly change the perceived position of pure-tone test
      stimuli in the low frequency region (128 and 256 Hz). CONCLUSIONS/SIGNIFICANCE:
      The findings in the current study indicate that ITD in the envelope at high
      frequencies induces the localization aftereffect. This suggests that ITD in the
      high frequency region is involved in adaptive plasticity of auditory localization
      processing.

PMID- 22848465
TI  - Receptor activator of NF-kappaB and podocytes: towards a function of a novel
      receptor-ligand pair in the survival response of podocyte injury.
AB  - BACKGROUND: Glomerulosclerosis correlates with reduction in podocyte number that
      occurs through mechanisms which include apoptosis. Podocyte injury or podocyte
      loss in the renal glomerulus has been proposed as the crucial mechanism in the
      development of glomerulosclerosis. However, the mechanism by which podocytes
      respond to injury is poorly understood. TNF and TNF receptor superfamilies are
      important in the pathogenesis of podocyte injury and apoptosis. The ligand of
      receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB
      (RANK) are members of the TNF and receptor superfamilies. We investigated whether
      RANK-RANKL is a receptor-ligand complex for podocytes responding to injury.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, RANKL and RANK were examined in
      human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis
      (PAN). Compared with controls, RANK and RANKL were increased in both human
      podocyte diseases and the rat PAN model; double immunofluorescence staining
      revealed that RANK protein expression was mainly attributed to podocytes.
      Immunoelectron microscopy showed that RANK was localized predominantly at the top
      of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK
      was upregulated in mouse podocytes in vitro after injury induced by puromycin
      aminonucleoside (PA). Knockdown of RANK expression by small interference RNA
      (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited
      significantly the apoptosis of podocytes induced by PA. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest the increase in RANK-RANKL expression is a response to
      podocyte injury, and RANK-RANKL may be a novel receptor-ligand complex for the
      survival response during podocyte injury.

PMID- 22848466
TI  - Fibroblast EXT1-levels influence tumor cell proliferation and migration in
      composite spheroids.
AB  - BACKGROUND: Stromal fibroblasts are important determinants of tumor cell
      behavior. They act to condition the tumor microenvironment, influence tumor
      growth, support tumor angiogenesis and affect tumor metastasis. Heparan sulfate
      proteoglycans, present both on tumor and stromal cells, interact with a large
      number of ligands including growth factors, their receptors, and structural
      components of the extracellular matrix. Being ubiquitously expressed in the tumor
      microenvironment heparan sulfate proteoglycans are candidates for playing central
      roles in tumor-stroma interactions. The objective of this work was to investigate
      the role of heparan sulfate expressed by stromal fibroblasts in modulating the
      growth of tumor cells and in controlling the interstitial fluid pressure in a 3-D
      model. METHODOLOGY/PRINCIPAL FINDINGS: We generated spheroids composed of
      fibroblasts alone, or composite spheroids, composed of fibroblasts and tumor
      cells. Here we show that stromal fibroblasts with a mutation in the heparan
      sulfate elongating enzyme Ext1 and thus a low heparan sulfate content, formed
      composite fibroblast/tumor cell spheroids with a significant lower interstitial
      fluid pressure than corresponding wild-type fibroblast/tumor cell composite
      spheroids. Furthermore, immunohistochemistry of composite spheroids revealed that
      the cells segregated, so that after 6 days in culture, the wild-type fibroblasts
      formed an inner core and the tumor cells an outer layer of cells. For composite
      spheroids containing Ext1-mutated fibroblasts this segregation was less obvious,
      indicating impaired cell migration. Analysis of tumor cells expressing the
      firefly luciferase gene revealed that the changes in tumor cell migration in
      mutant fibroblast/tumor cell composite spheroids coincided with a lower
      proliferation rate. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration
      that stromal Ext1-levels modulate tumor cell proliferation and affect the
      interstitial fluid pressure in a 3-D spheroid model. Learning how structural
      changes in stromal heparan sulfate influence tumor cells is essential for our
      understanding how non-malignant cells of the tumor microenvironment influence
      tumor cell progression.

PMID- 22848467
TI  - Regime shifts and weakened environmental gradients in open oak and pine
      ecosystems.
AB  - Fire suppression allows tree species that are intolerant of fire stress to
      increase their distribution, potentially resulting in disruption of historical
      species-environmental relationships. To measure changes between historical
      General Land Office surveys (1815 to 1850) and current USDA Forest Inventory and
      Assessment surveys (2004 to 2008), we compared composition, distribution, and
      site factors of 21 tree species or species groups in the Missouri Ozarks. We used
      24 environmental variables and random forests as a classification method to model
      distributions. Eastern redcedar, elms, maples, and other fire-sensitive species
      have increased in dominance in oak forests, with concurrent reductions by oak
      species; specific changes varied by ecological subsection. Ordinations displayed
      loss of separation between formerly distinctive oak and fire-sensitive tree
      species groups. Distribution maps showed decreased presence of disturbance
      dependent oak and pine species and increased presence of fire-sensitive species
      that generally expanded from subsections protected from fire along rivers to
      upland areas, except for eastern redcedar, which expanded into these subsections.
      Large scale differences in spatial gradients between past and present communities
      paralleled reduced influence of local topographic gradients in the varied relief
      of the Missouri Ozarks, as fire-sensitive species have moved to higher, drier,
      and sunnier sites away from riverine corridors. Due to changes in land use,
      landscapes in the Missouri Ozarks, eastern United States, and world-wide are
      changing from open oak and pine-dominated ecosystems to novel oak-mixed species
      forests, although at fine scales, forests are becoming more diverse in tree
      species today. Fire suppression weakened the influence by environmental gradients
      over species dominance, allowing succession from disturbance-dependent oaks to an
      alternative state of fire-sensitive species. Current and future research and
      conservation that rely on historical relationships and ecological principles
      based on disturbance across the landscape will need to incorporate modern
      interactions among species for resources into management plans and projections.

PMID- 22848469
TI  - Oligomeric forms of insulin amyloid aggregation disrupt outgrowth and complexity
      of neuron-like PC12 cells.
AB  - Formation of protein amyloid fibrils consists of a series of intermediates
      including oligomeric aggregates, proto-fibrillar structures, and finally mature
      fibrils. Recent studies show higher toxicity for oligomeric and proto-fibrillar
      intermediates of protein relative to their mature fibrils. Here the kinetic of
      the insulin amyloid fibrillation was evaluated using a variety of techniques
      including ThT fluorescence, Congo red absorbance, circular dichroism, and atomic
      force microscopy (AFM). The solution surface tension changes were attributed to
      hydrophobic changes in insulin structure and were detected by Du Nouy Ring
      method. Determination of the surface tension of insulin oligomeric, proto
      fibrillar and fibrillar forms indicated that the hydrophobicity of solution is
      enhanced by the formation of the oligomeric forms of insulin compared to other
      forms. In order to investigate the toxicity of the different forms of insulin we
      monitored morphological alterations of the differentiated neuron-like PC12 cells
      following incubation with native, oligomeric aggregates, proto-fibrillar, and
      fibrillar forms of insulin. The cell body area, average neurite length, neurite
      width, number of primary neurites, and percent of bipolar cells and node/primary
      neurite ratios were used to assess the growth and complexity of PC12 cells
      exposed to different forms of insulin. We observed that the oligomeric form of
      insulin impaired the growth and complexity of PC12 cells compared to other forms.
      Together our data suggest that the lower surface tension of oligomers and their
      perturbation affects the morphology of PC12 cells, mainly due to their enhanced
      hydrophobicity and detergent-like structures.

PMID- 22848468
TI  - Contact sensitizers induce skin inflammation via ROS production and hyaluronic
      acid degradation.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) represents a severe health problem
      with increasing worldwide prevalence. It is a T cell-mediated skin disease
      induced by protein-reactive organic and inorganic chemicals. A key feature of
      contact allergens is their ability to trigger an innate immune response that
      leads to skin inflammation. Previous evidence from the mouse contact
      hypersensitivity (CHS) model suggests a role for endogenous activators of innate
      immune signaling. Here, we analyzed the role of contact sensitizer induced ROS
      production and concomitant changes in hyaluronic acid metabolism on CHS
      responses. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vitro and in vivo ROS
      production using fluorescent ROS detection reagents. HA fragmentation was
      determined by gel electrophoresis. The influence of blocking ROS production and
      HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was
      analyzed in the murine CHS model. Here, we demonstrate that organic contact
      sensitizers induce production of reactive oxygen species (ROS) and a concomitant
      breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro
      inflammatory low molecular weight fragments in the skin. Importantly, inhibition
      of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well
      as elicitation of CHS. CONCLUSIONS/SIGNIFICANCE: These data identify an indirect
      mechanism of contact sensitizer induced innate inflammatory signaling involving
      the breakdown of the ECM and generation of endogenous danger signals. Our
      findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors
      in prevention and treatment of ACD.

PMID- 22848470
TI  - Human bocaviruses are not significantly associated with gastroenteritis: results
      of retesting archive DNA from a case control study in the UK.
AB  - Gastroenteritis is a common illness causing considerable morbidity and mortality
      worldwide. Despite improvements in detection methods, a significant diagnostic
      gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory
      infections, have also frequently been detected in stool samples in cases of
      gastroenteritis, and a tentative association between HBoVs, and in particular
      type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study
      was to determine the role of HBoVs in gastroenteritis, using archived DNA samples
      from the case-control Infectious Intestinal Disease Study (IID). DNA extracted
      from stool samples from 2,256 cases and 2,124 controls were tested for the
      presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV
      assay, and positive samples were then tested in genotype 1 to 3-specific assays.
      HBoV was detected in 7.4% but no significantly different prevalence was observed
      between cases and controls. In the genotype-specific assays 106 of the 324 HBoV
      positive samples were genotyped, with HBoV-1 predominantly found in controls
      whilst HBoV-2 was more frequently associated with cases of gastroenteritis
      (p<0.01). A significant proportion of HBoV positives could not be typed using the
      type specific assays, 67% of the total positives, and this was most likely due to
      low viral loads being present in the samples. However, the distribution of the
      untyped HBoV strains was no different between cases and controls. In conclusion,
      HBoVs, including HBoV-2 do not appear to be a significant cause of
      gastroenteritis in the UK population.

PMID- 22848471
TI  - Sensing the underground--ultrastructure and function of sensory organs in root
      feeding Melolontha melolontha (Coleoptera: Scarabaeinae) larvae.
AB  - INTRODUCTION: Below ground orientation in insects relies mainly on olfaction and
      taste. The economic impact of plant root feeding scarab beetle larvae gave rise
      to numerous phylogenetic and ecological studies. Detailed knowledge of the
      sensory capacities of these larvae is nevertheless lacking. Here, we present an
      atlas of the sensory organs on larval head appendages of Melolontha melolontha.
      Our ultrastructural and electrophysiological investigations allow annotation of
      functions to various sensory structures. RESULTS: Three out of 17 ascertained
      sensillum types have olfactory, and 7 gustatory function. These sensillum types
      are unevenly distributed between antennae and palps. The most prominent
      chemosensory organs are antennal pore plates that in total are innervated by
      approximately one thousand olfactory sensory neurons grouped into functional
      units of three-to-four. In contrast, only two olfactory sensory neurons innervate
      one sensillum basiconicum on each of the palps. Gustatory sensilla chaetica
      dominate the apices of all head appendages, while only the palps bear thermo
      /hygroreceptors. Electrophysiological responses to CO(2), an attractant for many
      root feeders, are exclusively observed in the antennae. Out of 54 relevant
      volatile compounds, various alcohols, acids, amines, esters, aldehydes, ketones
      and monoterpenes elicit responses in antennae and palps. All head appendages are
      characterized by distinct olfactory response profiles that are even enantiomer
      specific for some compounds. CONCLUSIONS: Chemosensory capacities in M.
      melolontha larvae are as highly developed as in many adult insects. We interpret
      the functional sensory units underneath the antennal pore plates as cryptic
      sensilla placodea and suggest that these perceive a broad range of secondary
      plant metabolites together with CO(2). Responses to olfactory stimulation of the
      labial and maxillary palps indicate that typical contact chemo-sensilla have a
      dual gustatory and olfactory function.

PMID- 22848472
TI  - Differential DNA methylation in purified human blood cells: implications for cell
      lineage and studies on disease susceptibility.
AB  - Methylation of cytosines at CpG sites is a common epigenetic DNA modification
      that can be measured by a large number of methods, now even in a genome-wide
      manner for hundreds of thousands of sites. The application of DNA methylation
      analysis is becoming widely popular in complex disorders, for example, to
      understand part of the "missing heritability". The DNA samples most readily
      available for methylation studies are derived from whole blood. However, blood
      consists of many functionally and developmentally distinct cell populations in
      varying proportions. We studied whether such variation might affect the
      interpretation of methylation studies based on whole blood DNA. We found in
      healthy male blood donors there is important variation in the methylation
      profiles of whole blood, mononuclear cells, granulocytes, and cells from seven
      selected purified lineages. CpG methylation between mononuclear cells and
      granulocytes differed for 22% of the 8252 probes covering the selected 343 genes
      implicated in immune-related disorders by genome-wide association studies, and at
      least one probe was differentially methylated for 85% of the genes, indicating
      that whole blood methylation results might be unintelligible. For individual
      genes, even if the overall methylation patterns might appear similar, a few CpG
      sites in the regulatory regions may have opposite methylation patterns (i.e.,
      hypo/hyper) in the main blood cell types. We conclude that interpretation of
      whole blood methylation profiles should be performed with great caution and for
      any differences implicated in a disorder, the differences resulting from varying
      proportions of white blood cell types should be considered.

PMID- 22848473
TI  - Prevalence of diabetes and pre-diabetes and associated risk factors among
      tuberculosis patients in India.
AB  - BACKGROUND: Diabetes mellitus (DM) is recognised as an important risk factor to
      tuberculosis (TB). India has high TB burden, along with rising DM prevalence.
      There are inadequate data on prevalence of DM and pre-diabetes among TB cases in
      India. Aim was to determine diabetes prevalence among a cohort of TB cases
      registered under Revised National Tuberculosis Control Program in selected TB
      units in Tamil Nadu, India, and assess pattern of diabetes management amongst
      known cases. METHODS: 827 among the eligible patients (n = 904) underwent HbA1c
      and anthropometric measurements. OGTT was done for patients without previous
      history of DM and diagnosis was based on WHO criteria. Details of current
      treatment regimen of TB and DM and DM complications, if any, were recorded. A
      pretested questionnaire was used to collect information on sociodemographics,
      habitual risk factors, and type of TB. FINDINGS: DM prevalence was 25.3% (95% CI
      22.6-28.5) and that of pre-diabetes 24.5% (95% CI 20.4-27.6). Risk factors
      associated with DM among TB patients were age (31-35, 36-40, 41-45, 46-50, >50
      years vs <30 years) [OR (95% CI) 6.75 (2.36-19.3); 10.46 (3.95-27.7); 18.63 (6.58
      52.7); 11.05 (4.31-28.4); 24.7 (9.73-62.7) (p<0.001)], positive family history of
      DM [3.08 (1.73-5.5) (p<0.001)], sedentary occupation [1.69 (1.10-2.59) (p =
      0.016)], and BMI (18.5-22.9, 23-24.9 and >=25 kg/m(2) vs <18.5 kg/m(2)) [2.03
      (1.32-3.12) (p = 0.001); 0.87 (0.31-2.43) (p = 0.78); 1.44 (0.54-3.8) (p =
      0.47)]; for pre-diabetes, risk factors were age (36-40, 41-45, 46-50, >50 years
      vs <30 years) [2.24 (1.1-4.55) (p = 0.026); 6.96 (3.3-14.7); 3.44 (1.83-6.48);
      4.3 (2.25-8.2) (p<0.001)], waist circumference [<90 vs. >=90 cm (men), <80 vs.
      >=80 cm (women)] [3.05 (1.35-6.9) (p = 0.007)], smoking [1.92 (1.12-3.28) (p =
      0.017)] and monthly income (5000-10,000 INR vs <5000 INR) [0.59 (0.37-0.94) (p =
      0.026)]. DM risk was higher among pulmonary TB [3.06 (1.69-5.52) (p<0.001)],
      especially sputum positive, than non-pulmonary TB. INTERPRETATION: Nearly 50% of
      TB patients had either diabetes or pre-diabetes.

PMID- 22848474
TI  - Correlation between multi-drug resistance-associated membrane transport in clonal
      cancer cells and the cell cycle phase.
AB  - Multidrug resistance driven by ABC membrane transporters is one of the major
      reasons for treatment failure in human malignancy. Some limited evidence has
      previously been reported on the cell cycle dependence of ABC transporter
      expression. However, it has never been demonstrated that the functional activity
      of these transporters correlates with the cell cycle position. Here, we studied
      the rate of intrinsic ABC transport in different phases of the cell cycle in
      cultured MCF-7 breast cancer cells. The rate was characterized in terms of the
      efflux kinetics from cells loaded with an ABC transporter substrate. As averaging
      the kinetics over a cell population could lead to errors, we studied kinetics of
      ABC transport at the single-cell level. We found that the rate of ABC transport
      in MCF-7 cells could be described by Michaelis-Menten kinetics with two classical
      parameters, V(max) and K(M). Each of these parameters showed similar unimodal
      distributions with different positions of maxima for cell subpopulations in the
      2c and 4c states. Compared to the 2c cells, the 4c cells exhibited greater V(max)
      values, indicating a higher activity of transport. They also exhibited a greater
      V(max)/K(M) ratio, indicating a higher efficiency of transport. Our findings
      suggest that cell cycle-related modulation of MDR may need to be taken into
      account when designing chemotherapy regimens which include cytostatic agents.

PMID- 22848475
TI  - Identifying controlling nodes in neuronal networks in different scales.
AB  - Recent studies have detected hubs in neuronal networks using degree, betweenness
      centrality, motif and synchronization and revealed the importance of hubs in
      their structural and functional roles. In addition, the analysis of complex
      networks in different scales are widely used in physics community. This can
      provide detailed insights into the intrinsic properties of networks. In this
      study, we focus on the identification of controlling regions in cortical networks
      of cats' brain in microscopic, mesoscopic and macroscopic scales, based on single
      objective evolutionary computation methods. The problem is investigated by
      considering two measures of controllability separately. The impact of the number
      of driver nodes on controllability is revealed and the properties of controlling
      nodes are shown in a statistical way. Our results show that the statistical
      properties of the controlling nodes display a concave or convex shape with an
      increase of the allowed number of controlling nodes, revealing a transition in
      choosing driver nodes from the areas with a large degree to the areas with a low
      degree. Interestingly, the community Auditory in cats' brain, which has sparse
      connections with other communities, plays an important role in controlling the
      neuronal networks.

PMID- 22848476
TI  - Gene expression from bronchoscopy obtained tumour samples as a predictor of
      outcome in advanced inoperable lung cancer.
AB  - BACKGROUND: Several studies have shown the prognostic and predictive potential of
      molecular markers in combined therapy for lung cancer. Most of them referred,
      however, to operable early stage NSCLC. The aim of the present study is to
      correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer
      specimens with clinical outcome of advanced lung cancer. METHODS: Bronchoscopy
      cancer specimens were taken from 123 patients with radiological diagnosis of
      advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell
      cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell
      neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group
      was heterogeneous with respect to clinical stage, performance of the patients and
      treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine,
      with Universal Probe Library (Roche) fluorescent probes. The genes selected for
      the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1,
      and CDKN1B. RESULTS: More than 50 ng of RNA (the amount considered sufficient for
      the analysis) was isolated in 82 out of 112 lung cancer specimens (73%),
      including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The
      highest Cohen's kappa coefficient for discrimination between small cell, squamous
      cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (kappa = 0.177, p =
      0.0041). A multivariate Cox regression model has shown a significant impact of
      clinical stage (p<0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p =
      0.03, RR = 2.11) expression on overall survival in a group of 60 patients with
      NSCLC. CONCLUSION: These results show the feasibility of multiple gene expression
      analysis in bronchoscopy obtained cancer specimens as prognostic markers in
      radiotherapy and chemotherapy for advanced lung cancer. A limiting factor was
      relatively high proportion of samples from which sufficient amount of RNA could
      not be isolated.

PMID- 22848477
TI  - Obesity or overweight is associated with worse pathological response to
      neoadjuvant chemotherapy among Chinese women with breast cancer.
AB  - BACKGROUND: To evaluate the relationship between body mass index (BMI) and
      response to neoadjuvant chemotherapy (NCT) for breast cancer among Chinese women.
      PATIENTS AND METHODS: A total of 307 eligible patients were assigned to receive
      four cycles of paclitaxel and carboplatin before standard surgery for breast
      cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were
      categorized as obese, overweight, normal weight, or underweight based on BMI
      according to World Health Organization (WHO) criteria. Pathological complete
      response (pCR) was defined as no invasive cancer in the breast or axillary
      tissue. A logistic regression and the Chi-squared test were used for detecting
      the predictors of pCR and determining the relationship between BMI category and
      pCR rate in the subgroup analysis with respect to other variables. RESULTS:
      Categorical BMI, estrogen receptor (ER), and progesterone receptor (PR) status
      were independent predictors of pCR according to the multivariate analysis.
      Patients with BMI>=25 were less likely to achieve a pCR to NCT compared with
      patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis). In
      the subgroup analysis, the predictive value of BMI for pCR to NCT was
      significantly shown in post-menopausal patients (p = 0.004) and hormonal receptor
      status-negative patients (p = 0.038). The incidence of treatment-induced toxicity
      was similar among the different BMI categories. CONCLUSION: Higher BMI was
      associated with worse pCR to NCT. Further approaches to investigating the
      mechanism of this influence of BMI on treatment response and a more appropriate
      schedule for calculating NCT dose for high-BMI-patients should be considered.

PMID- 22848478
TI  - Protection against enterovirus 71 with neutralizing epitope incorporation within
      adenovirus type 3 hexon.
AB  - Enterovirus 71 (EV71) is responsible for hand, foot and mouth disease with high
      mortality among children. Various neutralizing B cell epitopes of EV71 have been
      identified as potential vaccine candidates. Capsid-incorporation of antigens into
      adenovirus (Ad) has been developed for a novel vaccine approach. We constructed
      Ad3-based EV71 vaccine vectors by incorporating a neutralizing epitope SP70
      containing 15 amino acids derived from capsid protein VP1 of EV71 within the
      different surface-exposed domains of the capsid protein hexon of Ad3EGFP, a
      recombinant adenovirus type 3 (Ad3) expressing enhanced green fluorescence
      protein. Thermostability and growth kinetic assays suggested that the SP70
      epitope incorporation into hypervariable region (HVR1, HVR2, or HVR7) of the
      hexon did not affect Ad fitness. The SP70 epitopes were thought to be exposed on
      all hexon-modified intact virion surfaces. Repeated administration of BALB/c mice
      with the modified Ads resulted in boosting of the anti-SP70 humoral immune
      response. Importantly, the modified Ads immunization of mother mice conferred
      protection in vivo to neonatal mice against the lethal EV71 challenge, and the
      modified Ads-immunized mice serum also conferred passive protection against the
      lethal challenge in newborn mice. Compared with the recombinant GST-fused SP70
      protein immunization, immunization with the Ads containing SP70 in HVR1 or HVR2
      elicited higher SP70-specific IgG titers, higher neutralization titers, and
      conferred more effective protection to neonatal mice. Thus, this study provides
      valuable information for hexon-modified Ad3 vector development as a promising
      EV71 vaccine candidate and as an epitope-delivering vehicle for other pathogens.

PMID- 22848479
TI  - Occurrence of natural vertical transmission of dengue-2 and dengue-3 viruses in
      Aedes aegypti and Aedes albopictus in Fortaleza, Ceara, Brazil.
AB  - BACKGROUND: Aedes aegypti and Aedes albopictus perform an important role in the
      transmission of the dengue virus to human populations, particularly in the
      tropical and subtropical regions of the world. Despite a lack of understanding in
      relation to the maintenance of the dengue virus in nature during interepidemic
      periods, the vertical transmission of the dengue virus in populations of A.
      aegypti and A. albopictus appears to be of significance in relation to the urban
      scenario of Fortaleza. METHODS: From March 2007 to July 2009 collections of
      larvae and pupae of Aedes spp were carried out in 40 neighborhoods of Fortaleza.
      The collections yielded 3,417 (91%) A. aegypti mosquitoes and 336 (9%) A.
      albopictus mosquitoes. Only pools containing females, randomly chosen, were
      submitted to the following tests indirect immunofluorescence (virus isolation),
      RT-PCR/nested-PCR and nucleotide sequencing at the C-prM junction of the dengue
      virus genome. RESULTS: The tests on pool 34 (35 A. albopictus mosquitoes)
      revealed with presence of DENV-3, pool 35 (50 A. aegypti mosquitoes) was found to
      be infected with DENV-2, while pool 49 (41 A. albopictus mosquitoes) revealed the
      simultaneous presence of DENV-2 and DENV-3. Based on the results obtained, there
      was a minimum infection rate of 0.5 for A. aegypti and 9.4 for A. albopictus. The
      fragments of 192 bp and 152 bp related to DENV-3, obtained from pools 34 and 49,
      was registered in GenBank with the access codes HM130699 and JF261696,
      respectively. CONCLUSIONS: This study recorded the first natural evidence of the
      vertical transmission of the dengue virus in populations of A. aegypti and A.
      albopictus collected in Fortaleza, Ceara State, Brazil, opening a discuss on the
      epidemiological significance of this mechanism of viral transmission in the local
      scenario, particularly with respect to the maintenance of these viruses in nature
      during interepidemic periods.

PMID- 22848480
TI  - Sequencing of seven haloarchaeal genomes reveals patterns of genomic flux.
AB  - We report the sequencing of seven genomes from two haloarchaeal genera, Haloferax
      and Haloarcula. Ease of cultivation and the existence of well-developed genetic
      and biochemical tools for several diverse haloarchaeal species make haloarchaea a
      model group for the study of archaeal biology. The unique physiological
      properties of these organisms also make them good candidates for novel enzyme
      discovery for biotechnological applications. Seven genomes were sequenced to
      ~20*coverage and assembled to an average of 50 contigs (range 5 scaffolds-168
      contigs). Comparisons of protein-coding gene compliments revealed large-scale
      differences in COG functional group enrichment between these genera. Analysis of
      genes encoding machinery for DNA metabolism reveals genera-specific expansions of
      the general transcription factor TATA binding protein as well as a history of
      extensive duplication and horizontal transfer of the proliferating cell nuclear
      antigen. Insights gained from this study emphasize the importance of haloarchaea
      for investigation of archaeal biology.

PMID- 22848481
TI  - Similar evolution of cellular HIV-1 DNA level in darunavir/ritonavir monotherapy
      versus triple therapy in MONOI-ANRS136 trial over 96 weeks.
AB  - BACKGROUND: A higher proportion of intermittent viremia (to have a HIV-1 RNA
      viral load>50 copies/mL not confirmed) was reported in the boosted protease
      inhibitor monotherapy arm in some studies including MONOI trial, and that could
      have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA
      level is an interesting marker which reflects the size of cellular HIV reservoir.
      Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir
      monotherapy versus a triple standard combination on the HIV-1 blood reservoir and
      factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.
      METHODOLOGY/PRINCIPAL FINDINGS: This sub-study is focused on 160 patients (79
      patients in monotherapy arm and 81 in tritherapy arm) for whom blood cells were
      available both at baseline and at week 96 (W96). Baseline HIV-1 plasma DNA was
      associated with CD4 nadir, pre therapeutic HIV-1 RNA viral load and baseline HIV
      1 RNA measured by ultrasensitive assay. A similar median delta HIV-DNA was
      observed between D0 and W96 in both arms; 0.35 log copies/10(6) leucocytes in
      monotherapy arm versus 0.51 log copies/10(6) leucocytes in tritherapy arm.
      CONCLUSION/SIGNIFICANCE: Despite a higher proportion of intermittent viremia in
      monotherapy arm, a similar evolution of cellular HIV-1 DNA level was observed
      between mono and triple therapy arm. TRIAL REGISTRATION: ClinicalTrials. gov
      NCT00421551.

PMID- 22848482
TI  - Genipin inhibits mitochondrial uncoupling protein 2 expression and ameliorates
      podocyte injury in diabetic mice.
AB  - Diabetic nephropathy (DN) is one of the most common causes of end stage renal
      disease (ESRD) in China, which requires renal replacement therapy. Recent
      investigations have suggested an essential role of podocyte injury in the initial
      stage of DN. This study investigated the potential therapeutic role of genipin,
      an active extract from a traditional Chinese medicine, on progression of DN in
      diabetic mice induced by intraperitoneally injection of streptozocin (STZ). In
      diabetic mice, orally administration of genipin postponed the progression of DN,
      as demonstrated by ameliorating body weight loss and urine albumin leakage,
      attenuating glomerular basement membrane thickness, restoring the podocyte
      expression of podocin and WT1 in diabetic mice. The protective role of genipin on
      DN is probably through suppressing the up-regulation of mitochondrial uncoupling
      protein 2 (UCP2) in diabetic kidneys. Meanwhile, through inhibiting the up
      regulation of UCP2, genipin restores podocin and WT1 expression in cultured
      podocytes and attenuates glucose-induced albumin leakage through podocytes
      monolayer. Therefore, these results revealed that genipin inhibited UCP2
      expression and ameliorated podocyte injury in DN mice.

PMID- 22848483
TI  - Fluid flow along venous adventitia in rabbits: is it a potential drainage system
      complementary to vascular circulations?
AB  - BACKGROUND: Our previous research and other studies with radiotracers showed
      evidence of a centripetal drainage pathway, separate from blood or lymphatic
      vessels, that can be visualized when a small amount of low molecular weight
      tracer is injected subcutaneously into a given region on skin of humans. In order
      to further characterize this interesting biological phenomenon, animal
      experiments are designed to elucidate histological and physiologic
      characteristics of these visualized pathways. METHODS: Multiple tracers are
      injected subcutaneously into an acupuncture point of KI3 to visualize centripetal
      pathways by magnetic resonance imaging or fluorescein photography in 85 healthy
      rabbits. The pathways are compared with venography and indirect lymphangiography.
      Fluid flow through the pathways is observed by methods of altering their hydrated
      state, hydrolyzing by different collagenases, and histology is elucidated by
      optical, fluorescein and electron microscopy. RESULTS: Histological and magnetic
      imaging examinations of these visualized pathways show they consist of perivenous
      loose connective tissues. As evidenced by examinations of tracers' uptake, they
      appear to function as a draining pathway for free interstitial fluid. Fluorescein
      sodium from KI3 is found in the pathways of hind limbs and segments of the small
      intestines, partial pulmonary veins and results in pericardial effusion,
      suggesting systematical involvement of this perivenous pathway. The hydraulic
      conductivity of these pathways can be compromised by the collapse of their fiber
      rich beds hydrolyzed by either of collagenase type I, III, IV or V. CONCLUSIONS:
      The identification of pathways comprising perivenous loose connective tissues
      with a high hydraulic conductivity draining interstitial fluid in hind limbs of a
      mammal suggests a potential drainage system complementary to vascular
      circulations. These findings may provide new insights into a systematically
      distributed collagenous connective tissue with a circulatory function and their
      potential relevance to the nature of acupuncture meridians.

PMID- 22848484
TI  - The heterogeneous HLA genetic makeup of the Swiss population.
AB  - This study aims at investigating the HLA molecular variation across Switzerland
      in order to determine possible regional differences, which would be highly
      relevant to several purposes: optimizing donor recruitment strategies in
      hematopoietic stem cell transplantation (HSCT), providing reliable reference data
      in HLA and disease association studies, and understanding the population genetic
      background(s) of this culturally heterogeneous country. HLA molecular data of
      more than 20,000 HSCT donors from 9-13 recruitment centers of the whole country
      were analyzed. Allele and haplotype frequencies were estimated by using new
      computer tools adapted to the heterogeneity and ambiguity of the data. Non
      parametric and resampling statistical tests were performed to assess Hardy
      Weinberg equilibrium, selective neutrality and linkage disequilibrium among
      different loci, both in each recruitment center and in the whole national
      registry. Genetic variation was explored through genetic distance and
      hierarchical analysis of variance taking into account both geographic and
      linguistic subdivisions in Switzerland. The results indicate a heterogeneous
      genetic makeup of the Swiss population: first, allele frequencies estimated on
      the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by
      contrast with the results obtained for individual centers; second, a pronounced
      differentiation is observed for Ticino, Graubunden, and, to a lesser extent,
      Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally,
      although cultural (linguistic) boundaries do not represent a main genetic
      differentiation factor in Switzerland, the genetic relatedness between population
      from south-eastern Switzerland and Italy agrees with historical and linguistic
      data. Overall, this study justifies the maintenance of a decentralized donor
      recruitment structure in Switzerland allowing increasing the genetic diversity of
      the national--and hence global--donor registry. It also indicates that HLA data
      of local donor recruitment centers can be used as reference data in both
      epidemiological and population genetic studies focusing on the genetic history of
      present European populations.

PMID- 22848485
TI  - Sampling site matters when counting lymphocyte subpopulations.
AB  - Clinical and scientific work routinely relies on antecubital venipunctures for
      hematological, immunological or other analyses on blood. This study tested the
      hypothesis that antecubital veins can be considered to be a good proxy for other
      sampling sites. Using a hematocytometer and a flow cytometer, we analyzed the
      cell counts from samples coming from the radial artery, the dorsal hand veins and
      the antecubital veins from 18 volunteers. Most surprisingly, we identified the
      greatest difference not to exist between arterial and venous circulation, but
      between the distal (radial artery & dorsal hand veins) and proximal (antecubital
      veins) sampling sites. Naive T cells had a higher cell count distally compared to
      proximally and the reverse was true for effector memory T cells. Despite these
      differences there were high correlations between the different sampling sites,
      which partially supports our initial hypothesis. Our findings are crucial for the
      future design and interpretation of immunological research, and for clinical
      practice. Furthermore, our results suggest a role for interval lymph nodes in the
      trafficking of lymphocytes.

PMID- 22848486
TI  - Autophagy and apoptosis act as partners to induce germ cell death after heat
      stress in mice.
AB  - Testicular heating suppresses spermatogenesis which is marked by germ cell loss
      via apoptotic pathways. Recently, it is reported that autophagy also can be
      induced by heat treatment in somatic cells. In this study, the status of
      autophagy in germ cells after heat treatment, as well as the partnership between
      autophagy and apoptosis in these cells was investigated. The results demonstrated
      that besides initiating apoptotic pathways, heat also induced autophagic pathways
      in germ cells. Exposure of germ cells to hyperthermia resulted in several
      specific features of the autophagic process, including autophagosome formation
      and the conversion of LC3-I to LC3-II. Furthermore, the ubiquitin-like protein
      conjugation system was implicated as being likely responsible for heat-induced
      autophagy in germ cells since all genes involving this system were found to be
      expressed in the testes. In addition, the upstream protein in this system, Atg7
      (Autophagy-related gene 7), was found to be expressed in all types of
      spermatogenic cells, and its expression level was positively correlated with the
      level of autophagy in germ cells. As a result, Atg7 was selected as the
      investigative target to further analyze the role of autophagy in heat-induced
      germ cell death. It was shown that down expression of Atg7 protein resulted in
      the notable decrease in the level of autophagy in heat-treated germ cells, and
      this down-regulation of autophagy caused by Atg7 knockdown further reduced the
      apoptotic rate of germ cells. These results suggest that autophagy plays a
      positive role in the process of germ cell apoptosis after heat treatment. In
      conclusion, this study demonstrates that heat triggers autophagy and apoptosis in
      germ cells. These two mechanisms might act as partners, not antagonist, to induce
      cell death and lead to eventual destruction of spermatogenesis.

PMID- 22848487
TI  - Automated screening of microtubule growth dynamics identifies MARK2 as a
      regulator of leading edge microtubules downstream of Rac1 in migrating cells.
AB  - Polarized microtubule (MT) growth in the leading edge is critical to directed
      cell migration, and is mediated by Rac1 GTPase. To find downstream targets of
      Rac1 that affect MT assembly dynamics, we performed an RNAi screen of 23 MT
      binding and regulatory factors and identified RNAi treatments that suppressed
      changes in MT dynamics induced by constitutively activated Rac1. By analyzing
      fluorescent EB3 dynamics with automated tracking, we found that RNAi treatments
      targeting p150(glued), APC2, spastin, EB1, Op18, or MARK2 blocked Rac1-mediated
      MT growth in lamellipodia. MARK2 was the only protein whose RNAi targeting
      additionally suppressed Rac1 effects on MT orientation in lamellipodia, and thus
      became the focus of further study. We show that GFP-MARK2 rescued effects of
      MARK2 depletion on MT growth lifetime and orientation, and GFP-MARK2 localized in
      lamellipodia in a Rac1-activity-dependent manner. In a wound-edge motility assay,
      MARK2-depleted cells failed to polarize their centrosomes or exhibit oriented MT
      growth in the leading edge, and displayed defects in directional cell migration.
      Thus, automated image analysis of MT assembly dynamics identified MARK2 as a
      target regulated downstream of Rac1 that promotes oriented MT growth in the
      leading edge to mediate directed cell migration.

PMID- 22848488
TI  - Existence of prophenoloxidase in wing discs: a source of plasma prophenoloxidase
      in the silkworm, Bombyx mori.
AB  - In insects, hemocytes are considered as the only source of plasma
      prophenoloxidase (PPO). PPO also exists in the hemocytes of the hematopoietic
      organ that is connected to the wing disc of Bombyx mori. It is unknown whether
      there are other cells or tissues that can produce PPO and release it into the
      hemolymph besides circulating hemocytes. In this study, we use the silkworm as a
      model to explore this possibility. Through tissue staining and biochemical
      assays, we found that wing discs contain PPO that can be released into the
      culture medium in vitro. An in situ assay showed that some cells in the cavity of
      wing discs have PPO1 and PPO2 mRNA. We conclude that the hematopoietic organ may
      wrongly release hemocytes into wing discs since they are connected through many
      tubes as repost in previous paper. In wing discs, the infiltrating hemocytes
      produce and release PPO probably through cell lysis and the PPO is later
      transported into hemolymph. Therefore, this might be another source of plasma PPO
      in the silkworm: some infiltrated hemocytes sourced from the hematopoietic organ
      release PPO via wing discs.

PMID- 22848489
TI  - Input-dependent wave attenuation in a critically-balanced model of cortex.
AB  - A number of studies have suggested that many properties of brain activity can be
      understood in terms of critical systems. However it is still not known how the
      long-range susceptibilities characteristic of criticality arise in the living
      brain from its local connectivity structures. Here we prove that a dynamically
      critically-poised model of cortex acquires an infinitely-long ranged
      susceptibility in the absence of input. When an input is presented, the
      susceptibility attenuates exponentially as a function of distance, with an
      increasing spatial attenuation constant (i.e., decreasing range) the larger the
      input. This is in direct agreement with recent results that show that waves of
      local field potential activity evoked by single spikes in primary visual cortex
      of cat and macaque attenuate with a characteristic length that also increases
      with decreasing contrast of the visual stimulus. A susceptibility that changes
      spatial range with input strength can be thought to implement an input-dependent
      spatial integration: when the input is large, no additional evidence is needed in
      addition to the local input; when the input is weak, evidence needs to be
      integrated over a larger spatial domain to achieve a decision. Such input
      strength-dependent strategies have been demonstrated in visual processing. Our
      results suggest that input-strength dependent spatial integration may be a
      natural feature of a critically-balanced cortical network.

PMID- 22848490
TI  - Low concentration of silver nanoparticles not only enhances the activity of
      horseradish peroxidase but alter the structure also.
AB  - Chemical synthesis of Ag-NPs was carried out using reduction method. The
      reduction mechanistic approach of silver ions was found to be a basic clue for
      the formation of the Ag-NPs. The nanoparticles were characterized by UV-vis, FT
      IR and TEM analysis. We had designed some experiments in support of our
      hypothesis, "low concentrations of novel nanoparticles (silver and gold)
      increases the activity of plant peroxidases and alter their structure also", we
      had used Ag-NPs and HRP as models. The immobilization/interaction experiment had
      demonstrated the specific concentration range of the Ag-NPs and within this
      range, an increase in HRP activity was reported. At 0.08 mM concentration of Ag
      NPs, 50% increase in the activity yield was found. The U.V-vis spectra had
      demonstrated the increase in the absorbance of HRP within the reported
      concentration range (0.06-0.12 mM). Above and below this concentration range
      there was a decrease in the activity of HRP. The results that we had found from
      the fluorescence spectra were also in favor of our hypothesis. There was a
      maximum increase in ellipticity and alpha-helix contents in the presence of 0.08
      mM concentration of Ag-NPs, demonstrated by circular dichroism (CD) spectra.
      Finally, incubation of a plant peroxidase, HRP with Ag-NPs, within the reported
      concentration range not only enhances the activity but also alter the structure.

PMID- 22848491
TI  - Genome-wide histone acetylation is altered in a transgenic mouse model of
      Huntington's disease.
AB  - In Huntington's disease (HD; MIM ID #143100), a fatal neurodegenerative disorder,
      transcriptional dysregulation is a key pathogenic feature. Histone modifications
      are altered in multiple cellular and animal models of HD suggesting a potential
      mechanism for the observed changes in transcriptional levels. In particular,
      previous work has suggested an important link between decreased histone
      acetylation, particularly acetylated histone H3 (AcH3; H3K9K14ac), and
      downregulated gene expression. However, the question remains whether changes in
      histone modifications correlate with transcriptional abnormalities across the
      entire transcriptome. Using chromatin immunoprecipitation paired with microarray
      hybridization (ChIP-chip), we interrogated AcH3-gene interactions genome-wide in
      striata of 12-week old wild-type (WT) and transgenic (TG) R6/2 mice, an HD mouse
      model, and correlated these interactions with gene expression levels. At the
      level of the individual gene, we found decreases in the number of sites occupied
      by AcH3 in the TG striatum. In addition, the total number of genes bound by AcH3
      was decreased. Surprisingly, the loss of AcH3 binding sites occurred within the
      coding regions of the genes rather than at the promoter region. We also found
      that the presence of AcH3 at any location within a gene strongly correlated with
      the presence of its transcript in both WT and TG striatum. In the TG striatum,
      treatment with histone deacetylase (HDAC) inhibitors increased global AcH3 levels
      with concomitant increases in transcript levels; however, AcH3 binding at select
      gene loci increased only slightly. This study demonstrates that histone H3
      acetylation at lysine residues 9 and 14 and active gene expression are intimately
      tied in the rodent brain, and that this fundamental relationship remains
      unchanged in an HD mouse model despite genome-wide decreases in histone H3
      acetylation.

PMID- 22848492
TI  - Endometrial stromal cells of women with recurrent miscarriage fail to
      discriminate between high- and low-quality human embryos.
AB  - BACKGROUND: The aetiology of recurrent miscarriage (RM) remains largely
      unexplained. Women with RM have a shorter time to pregnancy interval than
      normally fertile women, which may be due to more frequent implantation of non
      viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of
      women with RM discriminate less effectively between high-and low-quality human
      embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of
      normally fertile women. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of
      decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM
      and 6 fertile controls. Cell-free migration zones were created and the effect of
      the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5
      blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88
      trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18
      hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile
      or RM women was similar. In the presence of a low-quality embryo in the zone, the
      migration of H-EnSCs of control women was inhibited compared to the basal
      migration in the absence of an embryo (P<0.05) and compared to the migration in
      the presence of high-quality embryo (p<0.01). Interestingly, the migratory
      response H-EnSCs of women with RM did not differ between high- and low-quality
      embryos. Furthermore, in the presence of a spheroid their migration was enhanced
      compared to the H-EnSCs of controls (p<0.001). CONCLUSIONS: H-EnSCs of fertile
      women discriminate between high- and low-quality embryos whereas H-EnSCs of women
      with RM fail to do so. H-EnSCs of RM women have a higher migratory response to
      trophoblast spheroids. Future studies will focus on the mechanisms by which low
      quality embryos inhibit the migration of H-EnSCs and how this is deregulated in
      women with RM.

PMID- 22848493
TI  - qPMS7: a fast algorithm for finding (l, d)-motifs in DNA and protein sequences.
AB  - Detection of rare events happening in a set of DNA/protein sequences could lead
      to new biological discoveries. One kind of such rare events is the presence of
      patterns called motifs in DNA/protein sequences. Finding motifs is a challenging
      problem since the general version of motif search has been proven to be
      intractable. Motifs discovery is an important problem in biology. For example, it
      is useful in the detection of transcription factor binding sites and
      transcriptional regulatory elements that are very crucial in understanding gene
      function, human disease, drug design, etc. Many versions of the motif search
      problem have been proposed in the literature. One such is the (l, d)-motif search
      (or Planted Motif Search (PMS)). A generalized version of the PMS problem,
      namely, Quorum Planted Motif Search (qPMS), is shown to accurately model motifs
      in real data. However, solving the qPMS problem is an extremely difficult task
      because a special case of it, the PMS Problem, is already NP-hard, which means
      that any algorithm solving it can be expected to take exponential time in the
      worse case scenario. In this paper, we propose a novel algorithm named qPMS7 that
      tackles the qPMS problem on real data as well as challenging instances.
      Experimental results show that our Algorithm qPMS7 is on an average 5 times
      faster than the state-of-art algorithm. The executable program of Algorithm qPMS7
      is freely available on the web at http://pms.engr.uconn.edu/downloads/qPMS7.zip.
      Our online motif discovery tools that use Algorithm qPMS7 are freely available at
      http://pms.engr.uconn.edu or http://motifsearch.com.

PMID- 22848494
TI  - Mapping the mutual information network of enzymatic families in the protein
      structure to unveil functional features.
AB  - Amino acids committed to a particular function correlate tightly along evolution
      and tend to form clusters in the 3D structure of the protein. Consequently, a
      protein can be seen as a network of co-evolving clusters of residues. The goal of
      this work is two-fold: first, we have combined mutual information and structural
      data to describe the amino acid networks within a protein and their interactions.
      Second, we have investigated how this information can be used to improve methods
      of prediction of functional residues by reducing the search space. As a main
      result, we found that clusters of co-evolving residues related to the catalytic
      site of an enzyme have distinguishable topological properties in the network. We
      also observed that these clusters usually evolve independently, which could be
      related to a fail-safe mechanism. Finally, we discovered a significant enrichment
      of functional residues (e.g. metal binding, susceptibility to detrimental
      mutations) in the clusters, which could be the foundation of new prediction
      tools.

PMID- 22848495
TI  - First Epigravettian ceramic figurines from Europe (Vela Spila, Croatia).
AB  - Recent finds of 36 ceramic artifacts from the archaeological site of Vela Spila,
      Croatia, offer the first evidence of ceramic figurative art in late Upper
      Palaeolithic Europe, c. 17,500-15,000 years before present (BP). The size and
      diversity of this artistic ceramic assemblage indicate the emergence of a social
      tradition, rather than more ephemeral experimentation with a new material. Vela
      Spila ceramics offer compelling technological and stylistic comparisons with the
      only other evidence of a developed Palaeolithic ceramic tradition found at the
      sites of Pavlov I and Dolni Vestonice I, in the Czech Republic, c. 31,000-27,000
      cal BP. Because of the 10,000-year gap between the two assemblages, the Vela
      Spila ceramics are interpreted as evidence of an independent invention of this
      technology. Consequently, these artifacts provide evidence of a new social
      context in which ceramics developed and were used to make art in the Upper
      Palaeolithic.

PMID- 22848496
TI  - Identification of Bartonella Trw host-specific receptor on erythrocytes.
AB  - Each Bartonella species appears to be highly adapted to one or a limited number
      of reservoir hosts, in which it establishes long-lasting intraerythrocytic
      bacteremia as the hallmark of infection. Recently, we identified Trw as the
      bacterial system involved in recognition of erythrocytes according to their
      animal origin. The T4SS Trw is characterized by a multiprotein complex that spans
      the inner and outer bacterial membranes, and possesses a hypothetical pilus
      structure. TrwJ, I, H and trwL are present in variable copy numbers in different
      species and the multiple copies of trwL and trwJ in the Bartonella trw locus are
      considered to encode variant forms of surface-exposed pilus components. We
      therefore aimed to identify which of the candidate Trw pilus components were
      located on the bacterial surface and involved in adhesion to erythrocytes,
      together with their erythrocytic receptor. Using different technologies (electron
      microscopy, phage display, invasion inhibition assay, far western blot), we found
      that only TrwJ1 and TrwJ2 were expressed and localized at the cell surface of B.
      birtlesii and had the ability to bind to mouse erythrocytes, and that their
      receptor was band3, one of the major outer-membrane glycoproteins of
      erythrocytes, (anion exchanger). According to these results, we propose that the
      interaction between TrwJ1, TrwJ2 and band 3 leads to the critical host-specific
      adherence of Bartonella to its host cells, erythrocytes.

PMID- 22848497
TI  - Multiplex detection of B-type natriuretic peptide, cardiac troponin I and C
      reactive protein with photonic suspension array.
AB  - A novel photonic suspension array has been developed for multiplex immunoassay.
      The carriers of this array were silica colloidal crystal beads (SCCBs). The codes
      of these carriers have characteristic reflection peaks originating from their
      structural periodicity; therefore they do not suffer from fading, bleaching,
      quenching or chemical instability. In addition, the fluorescence background of
      SCCBs is negligible because no fluorescence materials or dyes are involved. With
      a sandwich method, the proposed suspension array was used for simultaneous
      multiplex detection of heart failure (HF) and coronary heart disease (CAD)
      biomarkers in one test tube. The results showed that the three biomarkers:
      cardiac troponin I (cTnI), C-reactive protein (CRP) and B-type natriuretic
      peptide (BNP) could be assayed in the ranges of 0.1-500 ng/ml, 1-500 mg/L and
      0.02-50 ng/ml with detection limits of 0.01 ng/ml, 0.36 mg/L and 0.004 ng/ml at
      3sigma, respectively. There were no significant differences between the photonic
      suspension array and traditional parallel single-analyte test. This novel method
      demonstrated acceptable accuracy, high detection sensitivity and reproducibility
      and excellent storage stability. This technique provides a new strategy for low
      cost, automated, and simultaneous multiplex immunoassays of bio-markers.

PMID- 22848498
TI  - Temporal separation of aggregation and ubiquitination during early inclusion
      formation in transgenic mice carrying the Huntington's disease mutation.
AB  - Abnormal insoluble ubiqitinated protein aggregates are found in the brains of
      Huntington's disease (HD) patients and in mice transgenic for the HTT mutation.
      Here, we describe the earliest stages of visible NII formation in brains of R6/2
      mice killed between 2 and 6 weeks of age. We found that huntingtin-positive
      aggregates formed rapidly (within 24-48 hours) in a spatiotemporal manner similar
      to that we described previously for ubiquitinated inclusions. However, in most
      neurons, aggregates are not ubiquitinated when they first form. It has always
      been assumed that mutant huntingtin is recognised as 'foreign' and consequently
      ubiquitinated and targeted for degradation by the ubiquitin-proteasome system
      pathway. Our data, however, suggest that aggregation and ubiquitination are
      separate processes, and that mutant huntingtin fragment is not recognized as
      'abnormal' by the ubiquitin-proteasome system before aggregation. Rather, mutant
      Htt appears to aggregate before it is ubiquitinated, and then either aggregated
      huntingtin is ubiquitinated or ubiquitinated proteins are recruited into
      aggregates. Our findings have significant implications for the role of the
      ubiquitin-proteasome system in the formation of aggregates, as they suggest that
      this system is not involved until after the first aggregates form.

PMID- 22848499
TI  - Integrative gene expression profiling reveals G6PD-mediated resistance to RNA
      directed nucleoside analogues in B-cell neoplasms.
AB  - The nucleoside analogues 8-amino-adenosine and 8-chloro-adenosine have been
      investigated in the context of B-lineage lymphoid malignancies by our
      laboratories due to the selective cytotoxicity they exhibit toward multiple
      myeloma (MM), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL)
      cell lines and primary cells. Encouraging pharmacokinetic and pharmacodynamic
      properties of 8-chloro-adenosine being documented in an ongoing Phase I trial in
      CLL provide additional impetus for the study of these promising drugs. In order
      to foster a deeper understanding of the commonalities between their mechanisms of
      action and gain insight into specific patient cohorts positioned to achieve
      maximal benefit from treatment, we devised a novel two-tiered chemoinformatic
      screen to identify molecular determinants of responsiveness to these compounds.
      This screen entailed: 1) the elucidation of gene expression patterns highly
      associated with the anti-tumor activity of 8-chloro-adenosine in the NCI-60 cell
      line panel, 2) characterization of altered transcript abundances between paired
      MM and MCL cell lines exhibiting differential susceptibility to 8-amino
      adenosine, and 3) integration of the resulting datasets. This approach generated
      a signature of seven unique genes including G6PD which encodes the rate
      determining enzyme of the pentose phosphate pathway (PPP), glucose-6-phosphate
      dehydrogenase. Bioinformatic analysis of primary cell gene expression data
      demonstrated that G6PD is frequently overexpressed in MM and CLL, highlighting
      the potential clinical implications of this finding. Utilizing the paired
      sensitive and resistant MM and MCL cell lines as a model system, we go on to
      demonstrate through loss-of-function and gain-of-function studies that elevated
      G6PD expression is necessary to maintain resistance to 8-amino- and 8-chloro
      adenosine but insufficient to induce de novo resistance in sensitive cells. Taken
      together, these results indicate that G6PD activity antagonizes the cytotoxicity
      of 8-substituted adenosine analogues and suggests that administration of these
      agents to patients with B-cell malignancies exhibiting normal levels of G6PD
      expression may be particularly efficacious.

PMID- 22848500
TI  - Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes.
AB  - BACKGROUND: Obesity and type 2 diabetes (T2DM) are associated with increased
      circulating free fatty acids and triacylglycerols. However, very little is known
      about specific molecular lipid species associated with these diseases. In order
      to gain further insight into this, we performed plasma lipidomic analysis in a
      rodent model of obesity and insulin resistance as well as in lean, obese and
      obese individuals with T2DM. METHODOLOGY/PRINCIPAL FINDINGS: Lipidomic analysis
      using liquid chromatography coupled to mass spectrometry revealed marked changes
      in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol
      and diacylglycerol species were elevated along with of a number of sphingolipids,
      a particularly interesting finding was the high fat diet (HFD)-induced reduction
      in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose
      tissue play an important role in metabolism, we next determined whether the HFD
      altered LPCs in these tissues. In contrast to our findings in plasma, only very
      modest changes in tissue LPCs were noted. To determine when the change in plasma
      LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of
      HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring
      within the first week. Consistent with our rodent model, data from our small
      human cohort showed a reduction in a number of LPC species in obese and obese
      individuals with T2DM. Interestingly, no differences were found between the obese
      otherwise healthy individuals and the obese T2DM patients. CONCLUSION:
      Irrespective of species, our lipidomic profiling revealed a generalized decrease
      in circulating LPC species in states of obesity. Moreover, our data indicate that
      diet and adiposity, rather than insulin resistance or diabetes per se, play an
      important role in altering the plasma LPC profile.

PMID- 22848501
TI  - Development of a small D-enantiomeric Alzheimer's amyloid-beta binding peptide
      ligand for future in vivo imaging applications.
AB  - Alzheimer's disease (AD) is a devastating disease affecting predominantly the
      aging population. One of the characteristic pathological hallmarks of AD are
      neuritic plaques, consisting of amyloid-beta peptide (Abeta). While there has
      been some advancement in diagnostic classification of AD patients according to
      their clinical severity, no fully reliable method for pre-symptomatic diagnosis
      of AD is available. To enable such early diagnosis, which will allow the
      initiation of treatments early in the disease progress, neuroimaging tools are
      under development, making use of Abeta-binding ligands that can visualize amyloid
      plaques in the living brain. Here we investigate the properties of a newly
      designed series of D-enantiomeric peptides which are derivatives of ACI-80,
      formerly called D1, which was developed to specifically bind aggregated Abeta1
      42. We describe ACI-80 derivatives with increased stability and Abeta binding
      properties, which were characterized using surface plasmon resonance and enzyme
      linked immunosorbent assays. The specific interactions of the lead compounds with
      amyloid plaques were validated by ex vivo immunochemistry in transgenic mouse
      models of AD. The novel compounds showed increased binding affinity and are
      promising candidates for further development into in vivo imaging compounds.

PMID- 22848502
TI  - Micronutrient requirements for growth and hydrocarbon production in the oil
      producing green alga Botryococcus braunii (Chlorophyta).
AB  - The requirements of micronutrients for biomass and hydrocarbon production in
      Botryococcus braunii UTEX 572 were studied using response surface methodology.
      The concentrations of four micronutrients (iron, manganese, molybdenum, and
      nickel) were manipulated to achieve the best performance of B. braunii in
      laboratory conditions. The responses of algal biomass and hydrocarbon to the
      concentration variations of the four micronutrients were estimated by a second
      order quadratic regression model. Genetic algorithm calculations showed that the
      optimal level of micronutrients for algal biomass were 0.266 uM iron, 0.707 uM
      manganese, 0.624 uM molybdenum and 3.38 uM nickel. The maximum hydrocarbon
      content could be achieved when the culture media contained 10.43 uM iron, 6.53 uM
      manganese, 0.012 uM molybdenum and 1.73 uM nickel. The validation through an
      independent test in a photobioreactor suggests that the modified media with
      optimised concentrations of trace elements can increase algal biomass by 34.5%
      and hydrocarbon by 27.4%. This study indicates that micronutrients play
      significant roles in regulating algal growth and hydrocarbon production, and the
      response surface methodology can be used to optimise the composition of culture
      medium in algal culture.

PMID- 22848503
TI  - Using the one-lung method to link p38 to pro-inflammatory gene expression during
      overventilation in C57BL/6 and BALB/c mice.
AB  - INTRODUCTION: The mechanisms of ventilator-induced lung injury (VILI), including
      the role of MAP kinases, are frequently studied in different mouse strains. A
      useful model for such studies is the isolated perfused mouse lung. As a further
      development we present the one-lung method that permits to continue perfusion and
      ventilation of the right lung after removal of the left lung. This method was
      used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory
      signaling events in two widely used mouse strains (C57BL/6, BALB/c) and to
      further define the role of p38 in VILI. METHODS: Lungs were perfused and
      ventilated for 30 min under control conditions before they were randomized to low
      (8 cm H(2)O) or high (25 cm H(2)O) pressure ventilation (HPV) for 210 min, with
      the left lung being removed after 180 min. In the left lung we measured the
      phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene
      expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg.
      RESULTS: Lung mechanics and kinase activation were similar in both mouse strains.
      HPV increased all genes (except Tnf in BALB/c) and all mediators in both strains.
      The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c
      mice. Backward regression of the kinase data at t = 180 min with the gene and
      protein expression data at t = 240 min suggested that p38 controls HPV-induced
      gene expression, but not protein production. This hypothesis was confirmed in
      experiments with the p38-kinase inhibitor SB203580. CONCLUSIONS: The one-lung
      method is useful for mechanistic studies in the lungs. While C57BL/6 show
      diminished pro-inflammatory responses during HPV, lung mechanics and
      mechanotransduction processes appear to be similar in both mouse strains.
      Finally, the one-lung method allowed us to link p38 to gene expression during
      VILI.

PMID- 22848504
TI  - Antisense oligonucleotide against hTERT (Cantide) inhibits tumor growth in an
      orthotopic primary hepatic lymphoma mouse model.
AB  - BACKGROUND: Human xenograft models, resulting from orthotopic transplantation
      (implantation into the anatomically correct site) of histologically intact tissue
      into animals, are important for investigating local tumor growth, vascular and
      lymphatic invasion at the primary tumor site and metastasis.
      METHODOLOGY/PRINCIPAL FINDINGS: We used surgical orthotopic transplantation to
      establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We
      performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and
      characterized the tumor cells. The maintenance of PHL characteristics were
      supported by immunohistochemical and cytogenetic analysis. We also report the
      antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide
      against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose
      dependent inhibition of tumor weight and serum LDH activity in the orthotopically
      transplanted animals by Cantide. Importantly, survival was prolonged in Cantide
      treated HLBL-0102 tumor-bearing mice when compared to mock-treated mice.
      CONCLUSIONS/SIGNIFICANCE: Our study provided the basis for the development of a
      clinical trial protocol to treat PHL.

PMID- 22848505
TI  - Wind and wildlife in the Northern Great Plains: identifying low-impact areas for
      wind development.
AB  - Wind energy offers the potential to reduce carbon emissions while increasing
      energy independence and bolstering economic development. However, wind energy has
      a larger land footprint per Gigawatt (GW) than most other forms of energy
      production and has known and predicted adverse effects on wildlife. The Northern
      Great Plains (NGP) is home both to some of the world's best wind resources and to
      remaining temperate grasslands, the most converted and least protected ecological
      system on the planet. Thus, appropriate siting and mitigation of wind development
      is particularly important in this region. Steering energy development to
      disturbed lands with low wildlife value rather than placing new developments
      within large and intact habitats would reduce impacts to wildlife. Goals for wind
      energy development in the NGP are roughly 30 GW of nameplate capacity by 2030.
      Our analyses demonstrate that there are large areas where wind development would
      likely have few additional impacts on wildlife. We estimate there are ~1,056 GW
      of potential wind energy available across the NGP on areas likely to have low
      impact for biodiversity, over 35 times development goals. New policies and
      approaches will be required to guide wind energy development to low-impact areas.

PMID- 22848506
TI  - TNF-overexpression in Borna disease virus-infected mouse brains triggers
      inflammatory reaction and epileptic seizures.
AB  - Proinflammatory state of the brain increases the risk for seizure development.
      Neonatal Borna disease virus (BDV)-infection of mice with neuronal overexpression
      of tumor necrosis factor-alpha (TNF) was used to investigate the complex
      relationship between enhanced cytokine levels, neurotropic virus infection and
      reaction pattern of brain cells focusing on its role for seizure induction. Viral
      antigen and glial markers were visualized by immunohistochemistry. Different
      levels of TNF in the CNS were provided by the use of heterozygous and homozygous
      TNF overexpressing mice. Transgenic TNF, total TNF (native and transgenic), TNF
      receptor (TNFR1, TNFR2), IL-1 and N-methyl-D-aspartate (NMDA)-receptor subunit 2B
      (NR2B) mRNA values were measured by real time RT-PCR. BDV-infection of TNF
      transgenic mice resulted in non-purulent meningoencephalitis accompanied by
      epileptic seizures with a higher frequency in homozygous animals. This correlated
      with lower weight gain, stronger degree and progression of encephalitis and
      early, strong microglia activation in the TNF-transgenic mice, most obviously in
      homozygous animals. Activation of astroglia could be more intense and associated
      with an unusual hypertrophy in the transgenic mice. BDV-antigen distribution and
      infectivity in the CNS was comparable in TNF-transgenic and wild-type animals.
      Transgenic TNF mRNA-expression was restricted to forebrain regions as the
      transgene construct comprised the promoter of NMDA-receptor subunit2B and induced
      up-regulation of native TNF mRNA. Total TNF mRNA levels did not increase
      significantly after BDV-infection in the brain of transgenic mice but TNFR1,
      TNFR2 and IL-1 mRNA values, mainly in the TNF overexpressing brain areas. NR2B
      mRNA levels were not influenced by transgene expression or BDV-infection.
      Neuronal TNF-overexpression combined with BDV-infection leads to cytokine up
      regulation, CNS inflammation and glial cell activation and confirmed the
      presensitizing effect of elevated cytokine levels for the development of
      spontaneous epileptic seizures when exposed to additional infectious noxi.

PMID- 22848507
TI  - Reproductive resilience to food shortage in a small heterothermic primate.
AB  - The massive energetic costs entailed by reproduction in most mammalian females
      may increase the vulnerability of reproductive success to food shortage.
      Unexpected events of unfavorable climatic conditions are expected to rise in
      frequency and intensity as climate changes. The extent to which physiological
      flexibility allows organisms to maintain reproductive output constant despite
      energetic bottlenecks has been poorly investigated. In mammals, reproductive
      resilience is predicted to be maximal during early stages of reproduction, due to
      the moderate energetic costs of ovulation and gestation relative to lactation. We
      experimentally tested the consequences of chronic-moderate and short-acute food
      shortages on the reproductive output of a small seasonally breeding primate, the
      grey mouse lemur (Microcebus murinus) under thermo-neutral conditions. These two
      food treatments were respectively designed to simulate the energetic constraints
      imposed by a lean year (40% caloric restriction over eight months) or by a
      sudden, severe climatic event occurring shortly before reproduction (80% caloric
      restriction over a month). Grey mouse lemurs evolved under the harsh,
      unpredictable climate of the dry forest of Madagascar and should thus display
      great potential for physiological adjustments to energetic bottlenecks. We
      assessed the resilience of the early stages of reproduction (mating success,
      fertility, and gestation) to these contrasted food treatments, and on the later
      stages (lactation and offspring growth) in response to the chronic food shortage
      only. Food deprived mouse lemurs managed to maintain constant most reproductive
      parameters, including oestrus timing, estrogenization level at oestrus, mating
      success, litter size, and litter mass as well as their overall number of
      surviving offspring at weaning. However, offspring growth was delayed in food
      restricted mothers. These results suggest that heterothermic, fattening-prone
      mammals display important reproductive resilience to energetic bottlenecks. More
      generally, species living in variable and unpredictable habitats may have evolved
      a flexible reproductive physiology that helps buffer environmental fluctuations.

PMID- 22848508
TI  - Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their
      interaction with obesity.
AB  - Obesity is a multifactorial disease caused by the interaction between genotype
      and environment, and it is considered to be a type of addictive alteration. The
      A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive
      disorders, with obesity and with the performance in executive functions. The 7
      repeat allele of the DRD4 gene has likewise been associated with the performance
      in executive functions, as well as with addictive behaviors and impulsivity.
      Participants were included in the obesity group (N = 42) if their body mass index
      (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was
      below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All
      subjects underwent neuropsychological assessment. Eating behavior traits were
      evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on
      almost all the executive variables, but no significant 'DRD4 7R-allele status'
      effects were observed for any of the executive variables analyzed. There was a
      significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on
      LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score.
      Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele
      of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of
      executive functions.

PMID- 22848509
TI  - Expression and stability of foreign epitopes introduced into 3A nonstructural
      protein of foot-and-mouth disease virus.
AB  - Foot-and-mouth disease virus (FMDV) is an aphthovirus that belongs to the
      Picornaviridae family and causes one of the most important animal diseases
      worldwide. The capacity of other picornaviruses to express foreign antigens has
      been extensively reported, however, little is known about FMDV. To explore the
      potential of FMDV as a viral vector, an 11-amino-acid (aa) HSV epitope and an 8
      aa FLAG epitope were introduced into the C-terminal different regions of 3A
      protein of FMDV full-length infectious cDNA clone. Recombinant viruses expressing
      the HSV or FLAG epitope were successfully rescued after transfection of both
      modified constructs. Immunofluorescence assay, Western blot and sequence analysis
      showed that the recombinant viruses stably maintained the foreign epitopes even
      after 11 serial passages in BHK-21 cells. The 3A-tagged viruses shared similar
      plaque phenotypes and replication kinetics to those of the parental virus. In
      addition, mice experimentally infected with the epitope-tagged viruses could
      induce tag-specific antibodies. Our results demonstrate that FMDV can be used
      effectively as a viral vector for the delivery of foreign tags.

PMID- 22848510
TI  - A new approach of personality and psychiatric disorders: a short version of the
      Affective Neuroscience Personality Scales.
AB  - BACKGROUND: The Affective Neuroscience Personality Scales (ANPS) is an instrument
      designed to assess endophenotypes related to activity in the core emotional
      systems that have emerged from affective neuroscience research. It
      operationalizes six emotional endophenotypes with empirical evidence derived from
      ethology, neural analyses and pharmacology: PLAYFULNESS/joy, SEEKING/interest,
      CARING/nurturance, ANGER/rage, FEAR/anxiety, and SADNESS/separation distress. We
      aimed to provide a short version of this questionnaire (ANPS-S).
      METHODOLOGY/PRINCIPAL FINDINGS: We used a sample of 830 young French adults which
      was randomly split into two subsamples. The first subsample was used to select
      the items for the short scales. The second subsample and an additional sample of
      431 Canadian adults served to evaluate the psychometric properties of the short
      instrument. The ANPS-S was similar to the long version regarding
      intercorrelations between the scales and gender differences. The ANPS-S had
      satisfactory psychometric properties, including factorial structure,
      unidimensionality of all scales, and internal consistency. The scores from the
      short version were highly correlated with the scores from the long version.
      CONCLUSIONS/SIGNIFICANCE: The short ANPS proves to be a promising instrument to
      assess endophenotypes for psychiatrically relevant science.

PMID- 22848511
TI  - Is an idea different from cake: can you have it and eat it, too? A violation of
      permanence in information consumption.
AB  - One of the basic features of information is permanence. This feature states that
      the consumption of information by one consumer does not affect the availability
      of that information to other consumers. We present examples in two studies
      indicating that both laymen and experts of information exchange may be motivated
      to make choices that violate the permanence feature in accepting (Study 1) and
      offering (Study 2) information. When they possess, but have not yet consumed
      information, people may suffer from the appearance of wastefulness. This apparent
      wastefulness may provide a potential explanation for the observed violation of
      the permanence feature. Our findings indicate that, as the material age evolves
      into the information age, information-exchange behavior has not evolved
      significantly away from material-exchange behavior.

PMID- 22848512
TI  - Percutaneous disc decompression with nucleoplasty-volumetry of the nucleus
      pulposus using ultrahigh-field MRI.
AB  - PURPOSE: To evaluate changes in nucleus pulposus volume as a potential parameter
      for the effects of disc decompression. METHODS: Fifty-two discs (T8 to L1) were
      extracted from 26 pigs and separated into thoracic (T8 to T11) and thoracolumbar
      discs (T12 to L1). The discs were imaged using 7.1 Tesla ultrahigh-field magnetic
      resonance imaging (MRI) with acquisition of axial T2-weighted turbo spin-echo
      sequences for determination of baseline and postinterventional nucleus pulposus
      volumes. Volumes were calculated using OsiriX(r) (http://www.osirix-viewer.com).
      After randomization, one group was treated with nucleoplasty, while the placebo
      group was treated with an identical procedure but without coblation current. The
      readers analyzing the MR images were blinded to the kind of procedure performed.
      Baseline and postinterventional volumes were compared between the nucleoplasty
      and placebo group. RESULTS: Average preinterventional nucleus volume was 0.799
      (SD: 0.212) ml. Postinterventional volume reduction in the nucleoplasty group was
      significant at 0.052 (SD: 0.035) ml or 6.30% (p<0.0001) (thoracic discs) and
      0.082 (SD: 0.042) ml or 7.25% (p = 0.0078) (thoracolumbar discs). Nucleoplasty
      achieved volume reductions of 0.114 (SD: 0.054) ml or 14.72% (thoracic) and 0.093
      (SD: 0.081) ml or 11.61% (thoracolumbar) compared with the placebo group.
      CONCLUSIONS: Nucleoplasty significantly reduces thoracic and thoracolumbar
      nucleus pulposus volumes in porcine discs.

PMID- 22848513
TI  - Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma
      (ESCC) in Eastern Chinese populations.
AB  - BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an
      important role in regulating DNA excision repair; its functional single
      nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute
      to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control
      study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer
      free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs,
      rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk
      of ESCC using unconditional logistic regression models. We also calculated false
      positive report probabilities (FPRPs) for significant findings. We found that
      compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were
      associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI =
      0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was
      not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in
      further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These
      findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in
      Eastern Chinese populations, but the effect was weak and needs further validation
      by larger population-based case-control studies.

PMID- 22848514
TI  - Effect of adjuvants on responses to skin immunization by microneedles coated with
      influenza subunit vaccine.
AB  - Recent studies have demonstrated the effectiveness of vaccine delivery to the
      skin by vaccine-coated microneedles; however there is little information on the
      effects of adjuvants using this approach for vaccination. Here we investigate the
      use of TLR ligands as adjuvants with skin-based delivery of influenza subunit
      vaccine. BALB/c mice received 1 ug of monovalent H1N1 subunit vaccine alone or
      with 1 ug of imiquimod or poly(I:C) individually or in combination via coated
      microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit
      influenza vaccine induced similar antigen-specific immune responses compared to
      vaccine alone when delivered to the skin by microneedles. However, imiquimod
      adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased
      hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced
      induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine
      induced a robust IFN-gamma cellular response. These responses correlated with
      improved protection compared to influenza subunit vaccine alone, as well as
      reduced viral replication and production of pro-inflammatory cytokines in the
      lungs. The finding that microneedle delivery of imiquimod with influenza subunit
      vaccine induces improved immune responses compared to vaccine alone supports the
      use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

PMID- 22848515
TI  - Functional characterization of a novel outer membrane porin KpnO, regulated by
      PhoBR two-component system in Klebsiella pneumoniae NTUH-K2044.
AB  - BACKGROUND: The diffusion of antibiotics through the outer membrane is primarily
      affected by the porin super family, changes contribute to antibiotic resistance.
      Recently we demonstrated that the CpxAR two-component signaling system alters the
      expression of an uncharacterized porin OmpC(KP), to mediate antimicrobial
      resistance in K. pneumoniae. PRINCIPAL FINDINGS: In this study, functional
      characterization of the putative porin OmpC(KP) (denoted kpnO) with respect to
      antimicrobial susceptibility and virulence was evaluated by generating an
      isogenic mutant, DeltakpnO in a clinical isolate of K. pneumoniae. Estimation of
      uronic acid content confirmed that DeltakpnO produced ~2.0 fold lesser capsular
      polysaccharide than the wild-type. The DeltakpnO displayed higher sensitivity to
      hyper osmotic and bile conditions. Disruption of kpnO increased the
      susceptibility of K. pneumoniae to oxidative and nitrostative stress by ~1.6 fold
      and >7 fold respectively. The loss of the Klebsiella porin led to an increase in
      the minimum inhibitory concentration of tetracycline (3-fold), nalidixic acid (4
      fold), tobramycin (4-fold), streptomycin (10-fold), and spectinomycin (10-fold),
      which could be restored following complementation. The single deletion of kpnO
      reduced the survival of the pathogen by 50% when exposed to disinfectants. In
      Caenorhabditis elegans model, the kpnO mutant exhibited significantly (P<0.01)
      lower virulence. To dissect the role of PhoBR signaling system in regulating the
      expression of the kpnO, a phoB(KP) isogenic mutant was constructed. The phoB(KP)
      mutant exhibited impaired gastrointestinal stress response and decreased
      antimicrobial susceptibility. The mRNA levels of kpnO were found to be 4-fold
      less in phoB(KP) mutant compared to wild type. A regulatory role of PhoB(KP) for
      the expression of kpnO was further supported by the specific binding of PhoB(KP)
      to the putative promoter of kpnO. CONCLUSIONS AND SIGNIFICANCE: Loss of PhoBR
      regulated porin KpnO resulted in increased antimicrobial resistance, increased
      susceptibility to gastrointestinal stress, and reduced virulence in K. pneumoniae
      NTUH-K2044.

PMID- 22848516
TI  - Tracking the emergence of a new breed using 49,034 SNP in sheep.
AB  - Domestic animals are unique in that they have been organised into managed
      populations called breeds. The strength of genetic divergence between breeds may
      vary dependent on the age of the breed, the scenario under which it emerged and
      the strength of reproductive isolation it has from other breeds. In this study,
      we investigated the Gulf Coast Native breed of sheep to determine if it contains
      lines of animals that are sufficiently divergent to be considered separate
      breeds. Allele sharing and principal component analysis (PCA) using nearly 50,000
      SNP loci revealed a clear genetic division that corresponded with membership of
      either the Florida or Louisiana Native lines. Subsequent analysis aimed to
      determine if the strength of the divergence exceeded that found between
      recognised breed pairs. Genotypes from 14 breeds sampled from Europe and Asia
      were used to obtain estimates of pair-wise population divergence measured as
      F(ST). The divergence separating the Florida and Louisiana Native (F(ST) = 6.2%)
      was approximately 50% higher than the average divergence separating breeds
      developed within the same region of Europe (F(ST) = 4.2%). This strongly
      indicated that the two Gulf Coast Native lines are sufficiently different to be
      considered separate breeds. PCA using small SNP sets successfully distinguished
      between the Florida and Louisiana Native animals, suggesting that allele
      frequency differences have accumulated across the genome. This is consistent with
      a population history involving geographic separation and genetic drift.
      Suggestive evidence was detected for divergence at the poll locus on sheep
      chromosome 10; however drift at neutral markers has been the largest contributor
      to the genetic separation observed. These results document the emergence of
      populations that can be considered separate breeds, with practical consequences
      for bio-conservation priorities, animal registration and the establishment of
      separate breed societies.

PMID- 22848518
TI  - Cell wall ingrowths in nematode induced syncytia require UGD2 and UGD3.
AB  - The cyst nematode Heterodera schachtii infects roots of Arabidopsis plants and
      establishes feeding sites called syncytia, which are the only nutrient source for
      nematodes. Development of syncytia is accompanied by changes in cell wall
      structures including the development of cell wall ingrowths. UDP-glucuronic acid
      is a precursor of several cell wall polysaccharides and can be produced by UDP
      glucose dehydrogenase through oxidation of UDP-glucose. Four genes in Arabidopsis
      encode this enzyme. Promoter::GUS analysis revealed that UGD2 and UGD3 were
      expressed in syncytia as early as 1 dpi while expression of UGD1 and UGD4 could
      only be detected starting at 2 dpi. Infection assays showed no differences
      between Deltaugd1 and Deltaugd4 single mutants and wild type plants concerning
      numbers of males and females and the size of syncytia and cysts. On single
      mutants of Deltaugd2 and Deltaugd3, however, less and smaller females, and
      smaller syncytia formed compared to wild type plants. The double mutant
      DeltaDeltaugd23 had a stronger effect than the single mutants. These data
      indicate that UGD2 and UGD3 but not UGD1 and UGD4 are important for syncytium
      development. We therefore studied the ultrastructure of syncytia in the
      DeltaDeltaugd23 double mutant. Syncytia contained an electron translucent
      cytoplasm with degenerated cellular organelles and numerous small vacuoles
      instead of the dense cytoplasm as in syncytia developing in wild type roots.
      Typical cell wall ingrowths were missing in the DeltaDeltaugd23 double mutant.
      Therefore we conclude that UGD2 and UGD3 are needed for the production of cell
      wall ingrowths in syncytia and that their lack leads to a reduced host
      suitability for H. schachtii resulting in smaller syncytia, lower number of
      developing nematodes, and smaller females.

PMID- 22848517
TI  - Diminished behavioral and neural sensitivity to sound modulation is associated
      with moderate developmental hearing loss.
AB  - The acoustic rearing environment can alter central auditory coding properties,
      yet altered neural coding is seldom linked with specific deficits to adult
      perceptual skills. To test whether developmental hearing loss resulted in
      comparable changes to perception and sensory coding, we examined behavioral and
      neural detection thresholds for sinusoidally amplitude modulated (sAM) stimuli.
      Behavioral sAM detection thresholds for slow (5 Hz) modulations were
      significantly worse for animals reared with bilateral conductive hearing loss
      (CHL), as compared to controls. This difference could not be attributed to
      hearing thresholds, proficiency at the task, or proxies for attention. Detection
      thresholds across the groups did not differ for fast (100 Hz) modulations, a
      result paralleling that seen in humans. Neural responses to sAM stimuli were
      recorded in single auditory cortex neurons from separate groups of awake animals.
      Neurometric analyses indicated equivalent thresholds for the most sensitive
      neurons, but a significantly poorer detection threshold for slow modulations
      across the population of CHL neurons as compared to controls. The magnitude of
      the neural deficit matched that of the behavioral differences, suggesting that a
      reduction of sensory information can account for limitations to perceptual
      skills.

PMID- 22848519
TI  - Sequence and copy number analyses of HEXB gene in patients affected by Sandhoff
      disease: functional characterization of 9 novel sequence variants.
AB  - Sandhoff disease (SD) is a lysosomal disorder caused by mutations in the HEXB
      gene. To date, 43 mutations of HEXB have been described, including 3 large
      deletions. Here, we have characterized 14 unrelated SD patients and developed a
      Multiplex Ligation-dependent Probe Amplification (MLPA) assay to investigate the
      presence of large HEXB deletions. Overall, we identified 16 alleles, 9 of which
      were novel, including 4 sequence variation leading to aminoacid changes [c.626C>T
      (p.T209I), c.634C>A (p.H212N), c.926G>T (p.C309F), c.1451G>A (p.G484E)] 3
      intronic mutations (c.1082+5G>A, c.1242+1G>A, c.1169+5G>A), 1 nonsense mutation
      c.146C>A (p.S49X) and 1 small in-frame deletion c.1260_1265delAGTTGA
      (p.V421_E422del). Using the new MLPA assay, 2 previously described deletions were
      identified. In vitro expression studies showed that proteins bearing aminoacid
      changes p.T209I and p.G484E presented a very low or absent activity, while
      proteins bearing the p.H212N and p.C309F changes retained a significant residual
      activity. The detrimental effect of the 3 novel intronic mutations on the HEXB
      mRNA processing was demonstrated using a minigene assay. Unprecedentedly,
      minigene studies revealed the presence of a novel alternative spliced HEXB mRNA
      variant also present in normal cells. In conclusion, we provided new insights
      into the molecular basis of SD and validated an MLPA assay for detecting large
      HEXB deletions.

PMID- 22848520
TI  - Leptin counteracts the hypoxia-induced inhibition of spontaneously firing
      hippocampal neurons: a microelectrode array study.
AB  - Besides regulating energy balance and reducing body-weight, the adipokine leptin
      has been recently shown to be neuroprotective and antiapoptotic by promoting
      neuronal survival after excitotoxic and oxidative insults. Here, we investigated
      the firing properties of mouse hippocampal neurons and the effects of leptin
      pretreatment on hypoxic damage (2 hours, 3% O(2)). Experiments were carried out
      by means of the microelectrode array (MEA) technology, monitoring hippocampal
      neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions,
      hippocampal neurons were spontaneously firing, either with prevailing isolated
      and randomly distributed spikes (11 DIV), or with patterns characterized by
      synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the
      spontaneous activity of hippocampal neurons, reducing their firing frequency by
      54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing
      activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic
      neurons and contrasted the hypoxia-induced depressive action, either by limiting
      the firing frequency reduction (at both ages) or by increasing it to 126% (in
      younger neurons). In order to find out whether leptin exerts its effect by
      activating large conductance Ca(2+)-activated K(+) channels (BK), as shown on rat
      hippocampal neurons, we applied the BK channel blocker paxilline (1 uM). Our data
      show that paxilline reversed the effects of leptin, both on normoxic and hypoxic
      neurons, suggesting that the adipokine counteracts hypoxia through BK channels
      activation in mouse hippocampal neurons.

PMID- 22848521
TI  - The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent
      coupling.
AB  - Connexin36 (Cx36) plays an important role in insulin secretion by controlling the
      intercellular synchronization of Ca(2+) transients induced during stimulation.
      The lack of drugs acting on Cx36 channels is a major limitation in further
      unraveling the molecular mechanism underlying this effect. To screen for such
      drugs, we have developed an assay allowing for a semi-automatic, fluorimetric
      quantification of Ca(2+) transients in large populations of MIN6 cells. Here, we
      show that (1) compared to control cells, MIN6 cells with reduced Cx36 expression
      or function showed decreased synchrony of glucose-induced Ca(2+) oscillations;
      (2) glibenclamide, a sulphonylurea which promotes Cx36 junctions and coupling,
      increased the number of synchronous MIN6 cells, whereas quinine, an antimalarial
      drug which inhibits Cx36-dependent coupling, decreased this proportion; (3)
      several drugs were identified that altered the intercellular Ca(2+)
      synchronization, cell coupling and distribution of Cx36; (4) some of them also
      affected insulin content. The data indicate that the intercellular
      synchronization of Ca(2+) oscillations provides a reliable and non-invasive
      measurement of Cx36-dependent coupling, which is useful to identify novel drugs
      affecting the function of beta-cells, neurons, and neuron-related cells that
      express Cx36.

PMID- 22848522
TI  - Bait effects in sampling coral reef fish assemblages with stereo-BRUVs.
AB  - Baited underwater video techniques are increasingly being utilised for assessing
      and monitoring demersal fishes because they are: 1) non extractive, 2) can be
      used to sample across multiple habitats and depths, 3) are cost effective, 4)
      sample a broader range of species than many other techniques, 5) and with greater
      statistical power. However, an examination of the literature demonstrates that a
      range of different bait types are being used. The use of different types of bait
      can create an additional source of variability in sampling programs. Coral reef
      fish assemblages at the Houtman Abrolhos Islands, Western Australia, were sampled
      using baited remote underwater stereo-video systems. One-hour stereo-video
      recordings were collected for four different bait treatments (pilchards, cat
      food, falafel mix and no bait (control)) from sites inside and outside a targeted
      fishery closure (TFC). In total, 5209 individuals from 132 fish species belonging
      to 41 families were recorded. There were significant differences in the fish
      assemblage structure and composition between baited and non-baited treatments
      (P<0.001), while no difference was observed with species richness. Samples baited
      with cat food and pilchards contained similar ingredients and were found to
      record similar components of the fish assemblage. There were no significant
      differences in the fish assemblages in areas open or closed to fishing,
      regardless of the bait used. Investigation of five targeted species indicated
      that the response to different types of bait was species-specific. For example,
      the relative abundance of Pagrus auratus was found to increase in areas protected
      from fishing, but only in samples baited with pilchards and cat food. The results
      indicate that the use of bait in conjunction with stereo-BRUVs is advantageous.
      On balance, the use of pilchards as a standardised bait for stereo-BRUVs
      deployments is justified for use along the mid-west coast of Western Australia.

PMID- 22848523
TI  - The effect on human balance of standing with toe-extension.
AB  - BACKGROUND: Postural balance is vital for safely carrying out many daily
      activities, such as locomotion. The purpose of this study was to determine how
      changes in normal standing (NS) and standing with toe-extension (SWT) impact
      postural control during quiet standing. Furthermore, the research aimed to
      examine the extent to which the effect of these factors differed between genders.
      METHODOLOGY/PRINCIPAL FINDINGS: Thirty healthy young adults (age = 21.2+/-1.3 y;
      height = 1.63+/-0.07 m; mass = 56.0+/-9.3 kg) with no prior lower limb injuries
      participated in the study. A postural stability test using the Biodex Balance
      System was used for both NS and SWT conditions. The three measurements from the
      BBS were Overall Stability Index (OSI), Medial-Lateral Stability Index (MLSI) and
      Anterior-Posterior Stability Index (APSI). No significant difference was found
      between NS and SWT in the OSI, MLSI or APSI (F(2, 28) = 3.357, p = 0.077). The
      main difference between the stability index scores was significant (F(2, 28) =
      275.1, p<0.001). The Bonferroni post-hoc test showed significant differences
      between the OSI and MLSI (p<0.001); the OSI and APSI (p<0.001); and the MLSI and
      the APSI (p<0.001). Significant differences were found during NS (p<0.001), for
      the MLSI when compared with the APSI, but this was not found during the SWT
      condition. Additionally, no gender effects were proven to exist that altered
      postural sway during quiet standing. CONCLUSIONS/SIGNIFICANCE: This study reveals
      significant interaction between the stability indices measured; OSI, APSI and
      MLSI in both NS and SWT. Standing with toe extended does not have a significant
      impact on an individual's ability to control their balance during normal quiet
      standing. However, the findings revealed that the sway tendency in the medial
      lateral direction might serve as a factor in an individual's ability to regain
      balance.

PMID- 22848524
TI  - Identification of pathway deregulation--gene expression based analysis of
      consistent signal transduction.
AB  - Signaling pathways belong to a complex system of communication that governs
      cellular processes. They represent signal transduction from an extracellular
      stimulus via a receptor to intracellular mediators, as well as intracellular
      interactions. Perturbations in signaling cascade often lead to detrimental
      changes in cell function and cause many diseases, including cancer.
      Identification of deregulated pathways may advance the understanding of complex
      diseases and lead to improvement of therapeutic strategies. We propose Analysis
      of Consistent Signal Transduction (ACST), a novel method for analysis of
      signaling pathways. Our method incorporates information regarding pathway
      topology, as well as data on the position of every gene in each pathway. To
      preserve gene-gene interactions we use a subject-sampling permutation model to
      assess the significance of pathway perturbations. We applied our approach to nine
      independent datasets of global gene expression profiling. The results of ACST, as
      well as three other methods used to analyze signaling pathways, are presented in
      the context of biological significance and repeatability among similar, yet
      independent, datasets. We demonstrate the usefulness of using information of
      pathway structure as well as genes' functions in the analysis of signaling
      pathways. We also show that ACST leads to biologically meaningful results and
      high repeatability.

PMID- 22848525
TI  - Peptidomics of the agriculturally damaging larval stage of the cabbage root fly
      Delia radicum (Diptera: Anthomyiidae).
AB  - The larvae of the cabbage root fly induce serious damage to cultivated crops of
      the family Brassicaceae. We here report the biochemical characterisation of
      neuropeptides from the central nervous system and neurohemal organs, as well as
      regulatory peptides from enteroendocrine midgut cells of the cabbage maggot. By
      LC-MALDI-TOF/TOF and chemical labelling with 4-sulfophenyl isothiocyanate, 38
      peptides could be identified, representing major insect peptide families:
      allatostatin A, allatostatin C, FMRFamide-like peptides, kinin, CAPA peptides,
      pyrokinins, sNPF, myosuppressin, corazonin, SIFamide, sulfakinins, tachykinins,
      NPLP1-peptides, adipokinetic hormone and CCHamide 1. We also report a new peptide
      (Yamide) which appears to be homolog to an amidated eclosion hormone-associated
      peptide in several Drosophila species. Immunocytochemical characterisation of the
      distribution of several classes of peptide-immunoreactive neurons and
      enteroendocrine cells shows a very similar but not identical peptide distribution
      to Drosophila. Since peptides regulate many vital physiological and behavioural
      processes such as moulting or feeding, our data may initiate the pharmacological
      testing and development of new specific peptide-based protection methods against
      the cabbage root fly and its larva.

PMID- 22848526
TI  - Comparison between EQ-5D and SF-6D utility in rural residents of Jiangsu
      Province, China.
AB  - BACKGROUND: The SF-6D and EQ-5D are widely used generic index measures as health
      related quality of life. We assessed within-subject agreement between SF-6D and
      EQ-5D utilities with different preference weights, and their validities in
      measuring Chinese rural residents, before and after standardization scores.
      METHODOLOGY/PRINCIPAL FINDINGS: Rural residents over 18 years old were
      interviewed using EQ-5D and SF-6D in Jiangsu Province, China. EQ-5D utility
      scoring algorithms were used from three conversion tables from the United
      Kingdom, Japan, and the United States. Validities, Sensitivity and agreement
      between instruments were computed and compared. Factors affecting utility
      difference were explored with multiple liner regression models. Scores with
      standardization intervals of 0-1 in the two instruments were analyzed by the use
      of the above methods again. In 929 respondents, relative efficiency statistic and
      receiver operating characteristic curves analysis showed SF-6D to be the more
      efficient, followed by the EQ-5D model in Japan weights. Bland-Altman plot
      analysis showed paired SF-6D/EQ-5D in UK weights had better agreement. Though
      some risk factors were found, multiple liner regression demonstrated most
      coefficients were weaker than 0.2, and all R(2) values were less than 0.06.
      Standardization did not significantly influence these results except scores'
      value. CONCLUSIONS/SIGNIFICANCE: SF-6D and next EQ-5D in Japan weights could be
      used for Chinese rural residents. Further research with larger sample size of
      population is needed to establish and determine the feasibility of
      standardization score.

PMID- 22848527
TI  - Learning-related neuronal activation in the zebra finch song system nucleus HVC
      in response to the bird's own song.
AB  - Like many other songbird species, male zebra finches learn their song from a
      tutor early in life. Song learning in birds has strong parallels with speech
      acquisition in human infants at both the behavioral and neural levels. Forebrain
      nuclei in the 'song system' are important for the sensorimotor acquisition and
      production of song, while caudomedial pallial brain regions outside the song
      system are thought to contain the neural substrate of tutor song memory. Here, we
      exposed three groups of adult zebra finch males to either tutor song, to their
      own song, or to novel conspecific song. Expression of the immediate early gene
      protein product Zenk was measured in the song system nuclei HVC, robust nucleus
      of the arcopallium (RA) and Area X. There were no significant differences in
      overall Zenk expression between the three groups. However, Zenk expression in the
      HVC was significantly positively correlated with the strength of song learning
      only in the group that was exposed to the bird's own song, not in the other two
      groups. These results suggest that the song system nucleus HVC may contain a
      neural representation of a memory of the bird's own song. Such a representation
      may be formed during juvenile song learning and guide the bird's vocal output.

PMID- 22848528
TI  - Precipitation of calcium, magnesium, strontium and barium in tissues of four
      Acacia species (Leguminosae: Mimosoideae).
AB  - Precipitation of calcium in plants is common. There are abundant studies on the
      uptake and content of magnesium, strontium and barium, which have similar
      chemical properties to calcium, in comparison with those of calcium in plants,
      but studies on co-precipitation of these elements with calcium in plants are
      rare. In this study, we compared morphologies, distributional patterns, and
      elemental compositions of crystals in tissues of four Acacia species grown in the
      field as well as in the glasshouse. A comparison was also made of field-grown
      plants and glasshouse-grown plants, and of phyllodes of different ages for each
      species. Crystals of various morphologies and distributional patterns were
      observed in the four Acacia species studied. Magnesium, strontium and barium were
      precipitated together with calcium, mainly in phyllodes of the four Acacia
      species, and sometimes in branchlets and primary roots. These elements were most
      likely precipitated in forms of oxalate and sulfate in various tissues, including
      epidermis, mesophyll, parenchyma, sclerenchyma (fibre cells), pith, pith ray and
      cortex. In most cases, precipitation of calcium, magnesium, strontium and barium
      was biologically induced, and elements precipitated differed between soil types,
      plant species, and tissues within an individual plant; the precipitation was also
      related to tissue age. Formation of crystals containing these elements might play
      a role in regulating and detoxifying these elements in plants, and protecting the
      plants against herbivory.

PMID- 22848529
TI  - Germ cell development in the scleractinian coral Euphyllia ancora (Cnidaria,
      Anthozoa).
AB  - Sexual reproduction of scleractinian coral is among the most important means of
      establishing coral populations. However, thus far, little is known about the
      mechanisms underlying coral gametogenesis. To better understand coral germ cell
      development, we performed a histological analysis of gametogenesis in Euphyllia
      ancora and characterized the coral homolog of the Drosophila germline marker gene
      vasa. The histological analysis revealed that E. ancora gametogenesis occurs in
      the mesenterial mesoglea between the mesenterial filaments and the retractor
      muscle bands. The development of germ cells takes approximately one year in
      females and half a year in males. Staining of tissue sections with an antibody
      against E. ancora Vasa (Eavas) revealed anti-Eavas immunoreactivity in the
      oogonia, early oocyte, and developing oocyte, but only faint or undetectable
      reactivity in developing oocytes that were >150 um in diameters. In males, Eavas
      could be detected in the spermatogonia and primary spermatocytes but was only
      faintly detectable in the secondary spermatocytes, spermatids, and sperms.
      Furthermore, a reverse transcription-polymerase chain reaction analysis and
      Western blotting analysis of unfertilized mature eggs proved the presence of
      Eavas transcripts and proteins, suggesting that Eavas may be a maternal factor.
      Vasa may represent a germ cell marker for corals, and would allow us to
      distinguish germ cells from somatic cells in coral bodies that have no distinct
      organs.

PMID- 22848530
TI  - Establishment of induced pluripotent stem cells from centenarians for
      neurodegenerative disease research.
AB  - Induced pluripotent stem cell (iPSC) technology can be used to model human
      disorders, create cell-based models of human diseases, including
      neurodegenerative diseases, and in establishing therapeutic strategies. To detect
      subtle cellular abnormalities associated with common late-onset disease in iPSCs,
      valid control iPSCs derived from healthy donors free of serious late-onset
      diseases are necessary. Here, we report the generation of iPSCs from fibroblasts
      obtained immediately postmortem from centenarian donors (106- and 109-years-old)
      who were extremely healthy until an advanced age. The iPSCs were generated using
      a conventional method involving OCT4, SOX2, KLF4, and c-MYC, and then
      differentiated into neuronal cells using a neurosphere method. The expression of
      molecules that play critical roles in late-onset neurodegenerative diseases by
      neurons differentiated from the centenarian-iPSCs was compared to that of neurons
      differentiated from iPSCs derived from familial Alzheimer's disease and familial
      Parkinson's disease (PARK4: triplication of the alpha synuclein gene) patients.
      The results indicated that our series of iPSCs would be useful in
      neurodegeneration research. The iPSCs we describe, which were derived from donors
      with exceptional longevity who were presumed to have no serious disease risk
      factors, would be useful in longevity research and as valid super-controls for
      use in studies of various late-onset diseases.

PMID- 22848531
TI  - Serum 25-hydroxyvitamin D3 and D2 and non-clinical psychotic experiences in
      childhood.
AB  - OBJECTIVE: Non-clinical psychotic experiences are common and distressing. It has
      been hypothesized that early life vitamin D deficiency may be a risk factor for
      psychosis-related outcomes, but it is not known if circulating concentrations of
      25-hydroxyvitamin D (25(OH)D) during childhood are associated with psychosis
      related outcomes or whether the two different forms of 25(OH)D, (25(OH)D(3) and
      25(OH)D(2), have similar associations with psychosis-related outcomes. METHODS:
      We investigated the association between serum 25(OH)D(3) and 25(OH)D(2)
      concentrations and psychotic experiences in a prospective birth cohort study.
      Serum 25(OH)D(3) and 25(OH)D(2) concentrations were measured at mean age 9.8
      years and psychotic experiences assessed at mean age 12.8 years by a psychologist
      (N = 3182). RESULTS: Higher 25(OH)D(3) concentrations were associated with lower
      risk of definite psychotic experiences (adjusted odds ratio: OR (95% confidence
      interval: CI) 0.85 (0.75-0.95)). Higher concentrations of 25(OH)D(2) were
      associated with higher risk of suspected and definite psychotic experiences
      (adjusted odds ratio: OR (95% confidence interval: CI) 1.26 (1.11, 1.43)). Higher
      25(OD)D(2) concentrations were also weakly associated with definite psychotic
      experiences (adjusted OR (95% CI) 1.17 (0.96, 1.43), though with wide confidence
      intervals including the null value. CONCLUSIONS: Our findings of an inverse
      association of 25(OH)D(3) with definite psychotic experiences is consistent with
      the hypothesis that vitamin D may protect against psychosis-related outcomes.

PMID- 22848532
TI  - Postglacial colonization of the Qinling Mountains: phylogeography of the swelled
      vent frog (Feirana quadranus).
AB  - BACKGROUND: The influence of Pleistocene climatic fluctuations on intraspecific
      diversification in the Qinling-Daba Mountains of East Asia remains poorly
      investigated. We tested hypotheses concerning refugia during the last glacial
      maximum (LGM) in this region by examining the phylogeography of the swelled vent
      frog (Feirana quadranus; Dicroglossidae, Anura, Amphibia). METHODOLOGY/PRINCIPAL
      FINDINGS: We obtained complete mitochondrial ND2 gene sequences of 224
      individuals from 34 populations of Feirana quadranus for phylogeographic
      analyses. Additionally, we obtained nuclear tyrosinase gene sequences of 68 F.
      quadranus, one F. kangxianensis and three F. taihangnica samples to test for
      mitochondrial introgression among them. Phylogenetic analyses based on all genes
      revealed no introgression among them. Phylogenetic analyses based on ND2 datasets
      revealed that F. quadranus was comprised of six lineages which were separated by
      deep valleys; the sole exception is that the Main Qinling and Micang-Western
      Qinling lineages overlap in distribution. Analyses of population structure
      indicated restricted gene flow among lineages. Coalescent simulations and
      divergence dating indicated that the basal diversification within F. quadranus
      may be associated with the dramatic uplifts of the Tibetan Plateau during the
      Pliocene. Coalescent simulations indicated that Wuling, Daba, and Western Qinling
      Micang-Longmen Mountains were refugia for F. quadranus during the LGM.
      Demographic analyses indicated that the Daba lineage experienced population size
      increase prior to the LGM but the Main Qinling and the Micang-Western Qinling
      lineages expanded in population size and range after the LGM, and the other
      lineages almost have stable population size or slight slow population size
      decline. CONCLUSIONS/SIGNIFICANCE: The Qinling-Daba Mountains hosted three
      refugia for F. quadranus during the LGM. Populations that originated in the Daba
      Mountains colonized the Main Qinling Mountains after the LGM. Recent sharp
      expansion of the Micang-Western Qinling and Main Qinling lineages probably
      contribute to their present-day secondary contact.

PMID- 22848533
TI  - Survival, growth and reproduction of non-native Nile tilapia II: fundamental
      niche projections and invasion potential in the northern Gulf of Mexico.
AB  - Understanding the fundamental niche of invasive species facilitates our ability
      to predict both dispersal patterns and invasion success and therefore provides
      the basis for better-informed conservation and management policies. Here we focus
      on Nile tilapia (Oreochromis niloticus Linnaeus, 1758), one of the most widely
      cultured fish worldwide and a species that has escaped local aquaculture
      facilities to become established in a coastal-draining river in Mississippi
      (northern Gulf of Mexico). Using empirical physiological data, logistic
      regression models were developed to predict the probabilities of Nile tilapia
      survival, growth, and reproduction at different combinations of temperature (14
      and 30 degrees C) and salinity (0-60, by increments of 10). These predictive
      models were combined with kriged seasonal salinity data derived from multiple
      long-term data sets to project the species' fundamental niche in Mississippi
      coastal waters during normal salinity years (averaged across all years) and
      salinity patterns in extremely wet and dry years (which might emerge more
      frequently under scenarios of climate change). The derived fundamental niche
      projections showed that during the summer, Nile tilapia is capable of surviving
      throughout Mississippi's coastal waters but growth and reproduction were limited
      to river mouths (or upriver). Overwinter survival was also limited to river
      mouths. The areas where Nile tilapia could survive, grow, and reproduce increased
      during extremely wet years (2-368%) and decreased during extremely dry years (86
      92%) in the summer with a similar pattern holding for overwinter survival. These
      results indicate that Nile tilapia is capable of 1) using saline waters to gain
      access to other watersheds throughout the region and 2) establishing populations
      in nearshore, low-salinity waters, particularly in the western portion of coastal
      Mississippi.

PMID- 22848534
TI  - Protective role of p70S6K in intestinal ischemia/reperfusion injury in mice.
AB  - The mTOR signaling pathway plays a crucial role in the regulation of cell growth,
      proliferation, survival and in directing immune responses. As the intestinal
      epithelium displays rapid cell growth and differentiation and is an important
      immune regulatory organ, we hypothesized that mTOR may play an important role in
      the protection against intestinal ischemia reperfusion (I/R)-induced injury. To
      better understand the molecular mechanisms by which the mTOR pathway is altered
      by intestinal I/R, p70S6K, the major effector of the mTOR pathway, was
      investigated along with the effects of rapamycin, a specific inhibitor of mTOR
      and an immunosuppressant agent used clinically in transplant patients. In vitro
      experiments using an intestinal epithelial cell line and hypoxia/reoxygenation
      demonstrated that overexpression of p70S6K promoted cell growth and migration,
      and decreased cell apoptosis. Inhibition of p70S6K by rapamycin reversed these
      protective effects. In a mouse model of gut I/R, an increase of p70S6K activity
      was found by 5 min and remained elevated after 6 h of reperfusion. Inhibition of
      p70S6K by rapamycin worsened gut injury, promoted inflammation, and enhanced
      intestinal permeability. Importantly, rapamycin treated animals had a
      significantly increased mortality. These novel results demonstrate a key role of
      p70S6K in protection against I/R injury in the intestine and suggest a potential
      danger in using mTOR inhibitors in patients at risk for gut hypoperfusion.

PMID- 22848536
TI  - The use of expert opinion to assess the risk of emergence or re-emergence of
      infectious diseases in Canada associated with climate change.
AB  - Global climate change is predicted to lead to an increase in infectious disease
      outbreaks. Reliable surveillance for diseases that are most likely to emerge is
      required, and given limited resources, policy decision makers need rational
      methods with which to prioritise pathogen threats. Here expert opinion was
      collected to determine what criteria could be used to prioritise diseases
      according to the likelihood of emergence in response to climate change and
      according to their impact. We identified a total of 40 criteria that might be
      used for this purpose in the Canadian context. The opinion of 64 experts from
      academic, government and independent backgrounds was collected to determine the
      importance of the criteria. A weight was calculated for each criterion based on
      the expert opinion. The five that were considered most influential on disease
      emergence or impact were: potential economic impact, severity of disease in the
      general human population, human case fatality rate, the type of climate that the
      pathogen can tolerate and the current climatic conditions in Canada. There was
      effective consensus about the influence of some criteria among participants,
      while for others there was considerable variation. The specific climate criteria
      that were most likely to influence disease emergence were: an annual increase in
      temperature, an increase in summer temperature, an increase in summer
      precipitation and to a lesser extent an increase in winter temperature. These
      climate variables were considered to be most influential on vector-borne diseases
      and on food and water-borne diseases. Opinion about the influence of climate on
      air-borne diseases and diseases spread by direct/indirect contact were more
      variable. The impact of emerging diseases on the human population was deemed more
      important than the impact on animal populations.

PMID- 22848535
TI  - Prevalence and clonal distribution of pcpA, psrP and Pilus-1 among pediatric
      isolates of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths
      globally. The objective of this study was to determine the distribution and
      clonal type variability of three potential vaccine antigens: Pneumococcal serine
      rich repeat protein (PsrP), Pilus-1, and Pneumococcal choline binding protein A
      (PcpA) among pneumococcal isolates from children with invasive pneumococcal
      disease and healthy nasopharyngeal carriers. We studied by Real-Time PCR a total
      of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates
      among children (total = 547 strains) collected in Barcelona, Spain, from January
      2004 to July 2010. pcpA, psrP and pilus-1 were detected in 92.8%, 51.7% and 14.4%
      of invasive isolates and in 92.1%, 48.3% and 18% of carrier isolates,
      respectively. Within individual serotypes the prevalence of psrP and pilus-1 was
      highly dependent on the clonal type. pcpA was highly prevalent in all strains
      with the exception of those belonging to serotype 3 (33.3% in serotype 3 isolates
      vs. 95.1% in other serotypes; P<.001). psrP was significantly more frequent in
      those serotypes that are less apt to be detected in carriage than in disease;
      58.7% vs. 39.1% P<.001. Antibiotic resistance was associated with the presence of
      pilus-1 and showed a negative correlation with psrP. These results indicate that
      PcpA, and subsequently Psrp and Pilus-1 together might be good candidates to be
      used in a next-generation of multivalent pneumococcal protein vaccine.

PMID- 22848537
TI  - Matrix metalloproteinase-2 promotes alphavbeta3 integrin-mediated adhesion and
      migration of human melanoma cells by cleaving fibronectin.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is a key regulator in the
      migration of tumor cells. alphavbeta3 integrin has been reported to play a
      critical role in cell adhesion and regulate the migration of tumor cells by
      promoting MMP-2 activation. However, little is known about the effects of MMP-2
      on alphavbeta3 integrin activity and alphavbeta3 integrin-mediated adhesion and
      migration of tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: Human melanoma cells
      were seeded using an agarose drop model and/or subjected to in vitro analysis
      using immunofluorescence, adhesion, migration and invasion assays to investigate
      the relationship between active MMP-2 and alphavbeta3 integrin during the
      adhesion and migration of the tumor cells. We found that MMP-2 was localized at
      the leading edge of spreading cells before alphavbeta3 integrin. alphavbeta3
      integrin-mediated adhesion and migration of the tumor cells were inhibited by a
      MMP-2 inhibitor. MMP-2 cleaved fibronectin into small fragments, which promoted
      the adhesion and migration of the tumor cells. CONCLUSION/SIGNIFICANCE: MMP-2
      cleaves fibronectin into small fragments to enhance the adhesion and migration of
      human melanoma cells mediated by alphavbeta3 integrin. These results indicate
      that MMP-2 may guide the direction of the tumor cell migration.

PMID- 22848538
TI  - Inflammation drives dysbiosis and bacterial invasion in murine models of ileal
      Crohn's disease.
AB  - BACKGROUND AND AIMS: Understanding the interplay between genetic susceptibility,
      the microbiome, the environment and the immune system in Crohn's Disease (CD) is
      essential for developing optimal therapeutic strategies. We sought to examine the
      dynamics of the relationship between inflammation, the ileal microbiome, and host
      genetics in murine models of ileitis. METHODS: We induced ileal inflammation of
      graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris,
      low dose indomethacin (LDI; 0.1 mg/mouse), or high dose indomethacin (HDI; 1
      mg/mouse). The composition and spatial distribution of the mucosal microbiome was
      evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization.
      Mucosal E. coli were enumerated by quantitative PCR, and characterized by
      phylogroup, genotype and pathotype. RESULTS: Moderate to severe ileitis induced
      by T. gondii (day 8) and HDI caused a consistent shift from >95% gram +
      Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced
      microbial diversity and mucosal invasion by adherent and invasive E. coli,
      mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial
      invasion did not develop in mice with mild ileitis induced by Giardia muris.
      Superimposition of genetic susceptibility and T. Gondii infection revealed
      greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/
      ), and reduced dysbiosis in ileitis-resistant CCR2(-/-) mice. Abrogating
      inflammation with the CD therapeutic anti-TNF-alpha-mAb tempered dysbiosis and
      bacterial invasion. CONCLUSIONS: Acute ileitis induces dysbiosis and
      proliferation of mucosally invasive E. coli, irrespective of trigger and
      genotype. The identification of CCR2 as a target for therapeutic intervention,
      and discovery that host genotype and therapeutic blockade of inflammation impact
      the threshold and extent of ileal dysbiosis are of high relevance to developing
      effective therapies for CD.

PMID- 22848539
TI  - The role of anchor-tipped larval hairs in the organization of ant colonies.
AB  - The spatial organization within a social insect colony is a key component of
      colony life. It influences individual interaction rates, resource distribution,
      and division of labor within the nest. Yet studies of social insect behavior are
      most often carried out in artificial constructions, which may change worker
      behavior and colony organization. We observed how workers of the ant Pheidole
      rhea organized brood in nests with deep chambers and textured walls that were
      designed to mimic their natural constructions more closely. Instead of clumping
      larvae into piles on the chamber floor, workers suspended fourth-instar larvae
      from the vertical walls and ceiling of each chamber while young larvae and pupae
      were clumped at the base. Fourth-instar larvae possess five rows of anchor-tipped
      hairs on their dorsal side, and we predicted that these hairs functioned to
      attach larvae to the nest walls. We gave larvae "haircuts," where only the anchor
      tipped hairs were removed, and then tested their ability to adhere to a textured
      surface raised to an angle of 90 degrees  and then 120 degrees  with respect to
      the horizontal plane. Larvae whose hairs had been clipped came unattached in
      almost all trials, while larvae whose hairs remained intact stayed attached. This
      confirmed that anchor-tipped hairs functioned to attach larvae to the walls of
      the nest. The presence of anchor-tipped hairs is widespread and has been
      documented in at least 22 genera from the ant subfamily Myrmicinae, including
      species that occur in a variety of environments and represent a broad range of
      nesting habits. Based on our results, it is likely that many species exhibit this
      larval hanging behavior, and this could impact colony characteristics such as
      spatial organization and the care of developing larvae by nurse workers.

PMID- 22848540
TI  - LRP5 regulates development of lung microvessels and alveoli through the
      angiopoietin-Tie2 pathway.
AB  - Angiogenesis is crucial for lung development. Although there has been
      considerable exploration, the mechanism by which lung vascular and alveolar
      formation is controlled is still not completely understood. Here we show that low
      density lipoprotein receptor-related protein 5 (LRP5), a component of the Wnt
      ligand-receptor complex, regulates angiogenesis and alveolar formation in the
      lung by modulating expression of the angiopoietin (Ang) receptor, Tie2, in
      vascular endothelial cells (ECs). Vascular development in whole mouse lungs and
      in cultured ECs is controlled by LRP5 signaling, which is, in turn, governed by a
      balance between the activities of the antagonistic Tie2 ligands, Ang1 and Ang2.
      Under physiological conditions when Ang1 is dominant, LRP5 knockdown decreases
      Tie2 expression and thereby, inhibits vascular and alveolar development in the
      lung. Conversely, when Ang2 dominates under hyperoxia treatment in neonatal mice,
      high LRP5 and Tie2 expression suppress angiogenesis and lung development. These
      findings suggest that the LRP5-Tie2-Ang signaling axis plays a central role in
      control of both angiogenesis and alveolarization during postnatal lung
      development, and that deregulation of this signaling mechanism might lead to
      developmental abnormalities of the lung, such as are observed in bronchopulmonary
      dysplasia (BPD).

PMID- 22848541
TI  - On the origin of tremor in Parkinson's disease.
AB  - The exact origin of tremor in Parkinson's disease remains unknown. We explain why
      the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor
      generator and consider a conductance-based model of subthalamo-pallidal circuits
      embedded into a simplified representation of the basal ganglia-thalamo-cortical
      circuit to investigate the dynamics of this loop. We show how variation of the
      strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical
      loop (representing the decreasing dopamine level in Parkinson's disease) leads to
      the occurrence of tremor-like burst firing. These tremor-like oscillations are
      suppressed when the connections are modulated back to represent a higher dopamine
      level (as it would be the case in dopaminergic therapy), as well as when the
      basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative
      anti-parkinsonian surgeries). Thus, the proposed model provides an explanation
      for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The
      strengthening of the loop leads to tremor oscillations, while the weakening or
      disconnection of the loop suppresses them. The loop origin of parkinsonian tremor
      also suggests that new tremor-suppression therapies may have anatomical targets
      in different cortical and subcortical areas as long as they are within the basal
      ganglia-thalamo-cortical loop.

PMID- 22848542
TI  - Exercise training improves exercise capacity and quality of life in patients with
      inoperable or residual chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Aim of this prospective study was to evaluate the effects of exercise
      training in patients with inoperable or residual chronic thromboembolic pulmonary
      hypertension (CTEPH). METHODS: Thirty-five consecutive patients with invasively
      confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61+/-15 years,
      mean pulmonary artery pressure, 63+/-20 mmHg; primary inoperable n = 33,
      persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable
      disease-targeted medication received exercise training in-hospital for 3 weeks
      and continued at home for 15 weeks. Medication remained unchanged during the
      study period. Efficacy parameters have been evaluated at baseline, after 3 and 15
      weeks by blinded-observers. Survival rate has been evaluated in a follow-up
      period of median 36.4 months (interquartile range 26.6-46.6 months). RESULTS: All
      patients tolerated exercise training without severe adverse events. Patients
      significantly improved the mean distance walked in 6 minutes compared to baseline
      by 61+/-54 meters after 3 weeks (p<0.001) and by 71+/-70 meters after 15 weeks (p
      = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen
      consumption and maximal workload. NT-proBNP improved significantly after 3 weeks
      of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year
      survival rate was 94% and the 3-year-survival 86% respectively. CONCLUSION:
      Training as add-on to medical therapy may be effective in patients with CTEPH to
      improve work capacity, quality of life and further prognostic relevant parameters
      and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric
      randomized controlled studies are needed to confirm these promising results.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01398345.

PMID- 22848543
TI  - Electric field detection in sawfish and shovelnose rays.
AB  - In the aquatic environment, living organisms emit weak dipole electric fields,
      which spread in the surrounding water. Elasmobranchs detect these dipole electric
      fields with their highly sensitive electroreceptors, the ampullae of Lorenzini.
      Freshwater sawfish, Pristis microdon, and two species of shovelnose rays,
      Glaucostegus typus and Aptychotrema rostrata were tested for their reactions
      towards weak artificial electric dipole fields. The comparison of sawfishes and
      shovelnose rays sheds light on the evolution and function of the elongated
      rostrum ('saw') of sawfish, as both groups evolved from a shovelnose ray-like
      ancestor. Electric stimuli were presented both on the substrate (to mimic benthic
      prey) and suspended in the water column (to mimic free-swimming prey). Analysis
      of around 480 behavioural sequences shows that all three species are highly
      sensitive towards weak electric dipole fields, and initiate behavioural responses
      at median field strengths between 5.15 and 79.6 nV cm(-1). The response
      behaviours used by sawfish and shovelnose rays depended on the location of the
      dipoles. The elongation of the sawfish's rostrum clearly expanded their
      electroreceptive search area into the water column and enables them to target
      free-swimming prey.

PMID- 22848544
TI  - The potential of avian H1N1 influenza A viruses to replicate and cause disease in
      mammalian models.
AB  - H1N1 viruses in which all gene segments are of avian origin are the most frequent
      cause of influenza pandemics in humans; therefore, we examined the disease
      causing potential of 31 avian H1N1 isolates of American lineage in DBA/2J mice.
      Thirty of 31 isolates were very virulent, causing respiratory tract infection; 22
      of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic
      2009 H1N1 viruses. Preliminary studies in BALB/cJ mice and ferrets showed that 1
      of 4 isolates tested was more pathogenic than the pandemic 2009 H1N1 viruses in
      BALB/cJ mice, and 1 of 2 strains transmitted both by direct and respiratory
      droplet contact in ferrets. Preliminary studies of other avian subtypes (H2, H3,
      H4, H6, H10, H12) in DBA/2J mice showed lower pathogenicity than the avian H1N1
      viruses. These findings suggest that avian H1N1 influenza viruses are unique
      among influenza A viruses in their potential to infect mammals.

PMID- 22848545
TI  - The obesity-related peptide leptin sensitizes cardiac mitochondria to calcium
      induced permeability transition pore opening and apoptosis.
AB  - The obesity-related 16 kDa peptide leptin is synthesized primarily in white
      adipocytes although its production has been reported in other tissues including
      the heart. There is emerging evidence that leptin may contribute to cardiac
      pathology especially that related to myocardial remodelling and heart failure. In
      view of the importance of mitochondria to these processes, the goal of the
      present study is to determine the effect of leptin on mitochondria permeability
      transition pore opening and the potential consequence in terms of development of
      apoptosis. Experiments were performed using neonatal rat ventricular myocytes
      exposed to 3.1 nM (50 ng/ml) leptin for 24 hours. Mitochondrial transition pore
      opening was analyzed as the capacity of mitochondria to retain the dye calcein-AM
      in presence of 200 uM CaCl2. Leptin significantly increased pore opening although
      the effect was markedly more pronounced in digitonin-permeabilized myocytes in
      the presence of calcium with both effects prevented by the transition pore
      inhibitor sanglifehrin A. These effects were associated with increased apoptosis
      as evidenced by increased TUNEL staining and caspase 3 activity, both of which
      were prevented by the transition pore inhibitor sanglifehrin A. Leptin enhanced
      Stat3 activation whereas a Stat 3 inhibitor peptide prevented leptin-induced
      mitochondrial transition pore opening as well as the hypertrophic and pro
      apoptotic effects of the peptide. Inhibition of the RhoA/ROCK pathway prevented
      the hypertrophic response to leptin but had no effect on increased pore opening
      following leptin administration. We conclude that leptin can enhance calcium
      mediated, Stat3-dependent pro-apoptotic effects as a result of increased
      mitochondrial transition pore opening and independently of its hypertrophic
      actions. Leptin may therefore contribute to mitochondrial dysfunction and the
      development of apoptosis in the diseased myocardium particularly under conditions
      of excessive intracellular calcium accumulation.

PMID- 22848546
TI  - Promoter strength driving TetR determines the regulatory properties of Tet
      controlled expression systems.
AB  - Bacteria frequently rely on transcription repressors and activators to alter gene
      expression patterns in response to changes in the surrounding environment. Tet
      repressor (TetR) is a paradigm transcription factor that senses the environmental
      state by binding small molecule effectors, the tetracyclines. However, recently
      isolated peptides that act as inducers of TetR after having been fused to the C
      terminus of a carrier protein, suggest that TetR can also regulate gene
      expression in a signal-transduction pathway. For this shift in regulatory
      mechanism to be successful, induction of TetR must be sensitive enough to respond
      to an inducing protein expressed at its endogenous level. To determine this
      regulatory parameter, a synthetic Tet-regulated system was introduced into the
      human pathogen Salmonella enterica serovar Typhimurium and tested for
      inducibility by a peptide. Reporter gene expression was detected if the peptide
      containing carrier protein Thioredoxin 1 was strongly overproduced, but not if it
      was expressed at a level similar to the physiological level of Thioredoxin 1.
      This was attributed to high steady-state amounts of TetR which was expressed by
      the promoter of the chloramphenicol acetyl transferase gene (P(cat)). Reducing
      P(cat) strength either by directed or by random mutagenesis of its -10 element
      concomitantly reduced the intracellular amounts of TetR. Sensitive and
      quantitative induction of TetR by an inducing peptide, when it was fused to
      Thioredoxin 1 at its native locus in the genome, was only obtained with weak
      P(cat) promoter variants containing GC-rich -10 elements. A second important
      observation was that reducing the TetR steady-state level did not impair
      repression. This permits flexible adjustment of an inducible system's sensitivity
      simply by altering the expression level of the transcription factor. These two
      new layers of expression control will improve the quality and, thus, the
      applicability of the Tet and other regulatory systems.

PMID- 22848547
TI  - Retigeric acid B attenuates the virulence of Candida albicans via inhibiting
      adenylyl cyclase activity targeted by enhanced farnesol production.
AB  - Candida albicans, the most prevalent fungal pathogen, undergoes yeast-to-hyphal
      switch which has long been identified as a key fungal virulence factor. We showed
      here that the lichen-derived small molecule retigeric acid B (RAB) acted as an
      inhibitor that significantly inhibited the filamentation of C. albicans, leading
      to the prolonged survival of nematodes infected by C. albicans. Quantitative real
      time PCR analysis and intracellular cAMP measurement revealed RAB regulated the
      Ras1-cAMP-Efg1 pathway by reducing cAMP level to inhibit the hyphae formation.
      Confocal microscopic observation showed RAB induced the expression of Dpp3,
      synthesizing more farnesol, which was confirmed by gas chromatography-mass
      spectroscopy detection. An adenylyl cyclase activity assay demonstrated RAB could
      repress the activity of Cdc35 through stimulating farnesol synthesis, thus
      causing a decrease in cAMP synthesis, leading to retarded yeast-to-hyphal
      transition. Moreover, reduced levels of intracellular cAMP resulted in the
      inhibition of downstream adhesins. Together, these findings indicate that RAB
      stimulates farnesol production that directly inhibits the Cdc35 activity,
      reducing the synthesis of cAMP and thereby causing the disruption of the
      morphologic transition and attenuating the virulence of C. albicans. Our work
      illustrates the underlying mechanism of RAB-dependent inhibition of the yeast-to
      hyphal switch and provides a potential application in treating the infection of
      C. albicans.

PMID- 22848548
TI  - Influence of Mabs on PrP(Sc) formation using in vitro and cell-free systems.
AB  - PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the
      abnormal isoform. This process requires contact between the two proteins and
      implies that there may be critical contact sites that are important for
      conversion. We hypothesized that antibodies binding to either PrP(c)or PrP(Sc)
      would hinder or prevent the formation of the PrP(C)-PrP(Sc) complex and thus slow
      down or prevent the conversion process. Two systems were used to analyze the
      effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells
      persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein
      misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed,
      and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). The
      two systems yielded similar results, in most cases, and demonstrate that PrP
      specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)
      PrP(Sc) conversion process. Based on the numerous and varied Mabs analyzed, the
      inhibitory effect does not appear to be epitope specific, related to PrP(C)
      conformation, or to cell membrane localization, but is influenced by the targeted
      PrP region (amino vs carboxy).

PMID- 22848549
TI  - DMH1, a novel BMP small molecule inhibitor, increases cardiomyocyte progenitors
      and promotes cardiac differentiation in mouse embryonic stem cells.
AB  - The possibility of using cell-based therapeutics to treat cardiac failure has
      generated significant interest since the initial introduction of stem cell-based
      technologies. However, the methods to quickly and robustly direct stem cell
      differentiation towards cardiac cell types have been limited by a reliance on
      recombinant growth factors to provide necessary biological cues. We report here
      the use of dorsomorphin homologue 1 (DMH1), a second-generation small molecule
      BMP inhibitor based on dorsomorphin, to efficiently induce beating cardiomyocyte
      formation in mouse embryonic stem cells (ESCs) and to specifically upregulate
      canonical transcriptional markers associated with cardiac development. DMH1
      differs significantly from its predecessor by its ability to enrich for pro
      cardiac progenitor cells that respond to late-stage Wnt inhibition using XAV939
      and produce secondary beating cardiomyocytes. Our study demonstrates the utility
      of small molecules to complement existing in vitro cardiac differentiation
      protocols and highlights the role of transient BMP inhibition in
      cardiomyogenesis.

PMID- 22848550
TI  - Correlation between in vivo biofilm formation and virulence gene expression in
      Escherichia coli O104:H4.
AB  - The emergence of novel pathogens poses a major public health threat causing
      widespread epidemics in susceptible populations. The Escherichia coli O104:H4
      strain implicated in a 2011 outbreak in northern Germany caused the highest
      frequency of hemolytic uremic syndrome (HUS) and death ever recorded in a single
      E. coli outbreak. Therefore, it has been suggested that this strain is more
      virulent than other pathogenic E. coli (e.g., E. coli O157:H7). The E. coli
      O104:H4 outbreak strain possesses multiple virulence factors from both Shiga
      toxin (Stx)-producing E. coli (STEC) and enteroaggregative E. coli (EAEC), though
      the mechanism of pathogenesis is not known. Here, we demonstrate that E. coli
      O104:H4 produces a stable biofilm in vitro and that in vivo virulence gene
      expression is highest when E. coli O104:H4 overexpresses genes required for
      aggregation and exopolysaccharide production, a characteristic of bacterial cells
      residing within an established biofilm. Interrupting exopolysaccharide production
      and biofilm formation may therefore represent effective strategies for combating
      future E. coli O104:H4 infections.

PMID- 22848551
TI  - Disruption of arterial perivascular drainage of amyloid-beta from the brains of
      mice expressing the human APOE epsilon4 allele.
AB  - Failure of elimination of amyloid-beta (Abeta) from the brain and vasculature
      appears to be a key factor in the etiology of sporadic Alzheimer's disease (AD)
      and cerebral amyloid angiopathy (CAA). In addition to age, possession of an
      apolipoprotein E (APOE) epsilon4 allele is a strong risk factor for the
      development of sporadic AD. The present study tested the hypothesis that
      possession of the APOE epsilon4 allele is associated with disruption of
      perivascular drainage of Abeta from the brain and with changes in cerebrovascular
      basement membrane protein levels. Targeted replacement (TR) mice expressing the
      human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral
      injections of human Abeta(40). Abeta(40) aggregated in peri-arterial drainage
      pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Abeta
      deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3
      mice, at both 3- and 16-months of age, suggesting that clearance of Abeta was
      disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot
      analysis of vascular basement membrane proteins demonstrated significantly raised
      levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type
      mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between
      wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study
      suggest that APOE4 may increase the risk for AD through disruption and impedance
      of perivascular drainage of soluble Abeta from the brain. This effect may be
      mediated, in part, by changes in age-related expression of basement membrane
      proteins in the cerebral vasculature.

PMID- 22848553
TI  - Genome-wide linkage and association analysis identifies major gene loci for
      guttural pouch tympany in Arabian and German warmblood horses.
AB  - Equine guttural pouch tympany (GPT) is a hereditary condition affecting foals in
      their first months of life. Complex segregation analyses in Arabian and German
      warmblood horses showed the involvement of a major gene as very likely. Genome
      wide linkage and association analyses including a high density marker set of
      single nucleotide polymorphisms (SNPs) were performed to map the genomic region
      harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German
      warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non
      parametric multipoint linkage analyses showed genome-wide significance on horse
      chromosomes (ECA) 3 for German warmblood at 16-26 Mb and 34-55 Mb and for Arabian
      on ECA15 at 64-65 Mb. Genome-wide association analyses confirmed the linked
      regions for both breeds. In Arabian, genome-wide association was detected at 64
      Mb within the region with the highest linkage peak on ECA15. For German
      warmblood, signals for genome-wide association were close to the peak region of
      linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide
      association was 0.12 for the Arabian. In conclusion, the refinement of the
      regions with the Illumina equine SNP50 beadchip is an important step to unravel
      the responsible mutations for GPT.

PMID- 22848552
TI  - Zidovudine exposure in HIV-1 infected Tanzanian women increases mitochondrial DNA
      levels in placenta and umbilical cords.
AB  - BACKGROUND: Zidovudine (AZT) constitutes part of the recommended regimens for
      prevention and treatment of HIV-1 infection. At the same time, AZT as well as HIV
      1 infection itself may induce mitochondrial damage. In this study, we analyzed
      the impact of prenatal AZT-exposure on mitochondrial alterations in HIV-infected
      women and their infants. METHODS: Mitochondrial DNA (mtDNA) levels in placentas
      of HIV-1 infected Tanzanian women with and without prenatal AZT exposure, and in
      the umbilical cords of their AZT-exposed/unexposed infants were quantified using
      real-time PCR. Furthermore, we checked for the most common mitochondrial deletion
      in humans, the 4977 base pair deletion (dmtDNA4977) as a marker for mitochondrial
      stress. RESULTS: 83 women fulfilled the inclusion criteria. 30 women had been
      treated with AZT (median duration 56 days; IQR 43-70 days) while 53 women had not
      taken AZT during pregnancy. Baseline maternal characteristics in the two groups
      were similar. The median mtDNA levels in placentas and umbilical cords of women
      (311 copies/cell) and infants (190 copies/cell) exposed to AZT were significantly
      higher than in AZT-unexposed women (187 copies/cell; p = 0.021) and infants (127
      copies/cell; p = 0.037). The dmtDNA4977 was found in placentas of one woman of
      each group and in 3 umbilical cords of AZT-unexposed infants but not in umbilical
      cords of AZT-exposed infants. CONCLUSIONS: Antenatal AZT intake did not increase
      the risk for the common mitochondrial deletion dmtDNA4977. Our data suggests that
      AZT exposure elevates mtDNA levels in placentas and umbilical cords possibly by
      positively influencing the course of maternal HIV-1 infection.

PMID- 22848554
TI  - Body iron stores and heme-iron intake in relation to risk of type 2 diabetes: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Emerging evidence from biological and epidemiological
      studies has suggested that body iron stores and heme-iron intake may be related
      to the risk of type 2 diabetes (T2D). We aimed to examine the association of body
      iron stores and heme-iron intake with T2D risk by conducting a systematic review
      and meta-analysis of previously published studies. RESEARCH DESIGN AND METHODS:
      Systematic review and subsequent meta-analysis were conducted by searching
      MEDLINE database up to June 22, 2012 to identify studies that analyzed the
      association of body iron stores or dietary heme-iron intake with T2D risk. The
      meta-analysis was performed using the effect estimates and 95% confidence
      intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity
      among studies was examined using the I(2) and Q statistic. RESULTS: The meta
      analysis included 16 high-quality studies: 12 studies analyzed ferritin levels
      (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246
      T2D patients and 179,689 controls). The combined relative risk (RR) comparing the
      highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15-2.39) for
      prospective studies, 2.29 (95% CI: 1.48-3.54) for cross-sectional studies with
      heterogeneity (Q = 14.84, p = 0.01, I(2) = 66.3%; Q = 44.16, p<0.001, I(2) =
      88.7%). The combined RR comparing the highest and lowest category of heme-iron
      intake was 1.31 (95% CI: 1.21-1.43) with heterogeneity (Q = 1.39, p = 0.71, I(2)
      = 0%). No publication bias was found. Additional 15 studies that were of good
      quality, had significant results, and analyzed the association between body iron
      stores and T2D risk were qualitatively included in the systematic review.
      CONCLUSIONS: The meta-analysis and systematic review suggest that increased
      ferritin levels and heme-iron intake are both associated with higher risk of T2D.

PMID- 22848555
TI  - A homeostatic model of neuronal firing governed by feedback signals from the
      extracellular matrix.
AB  - Molecules of the extracellular matrix (ECM) can modulate the efficacy of synaptic
      transmission and neuronal excitability. These mechanisms are crucial for the
      homeostatic regulation of neuronal firing over extended timescales. In this
      study, we introduce a simple mathematical model of neuronal spiking balanced by
      the influence of the ECM. We consider a neuron receiving random synaptic input in
      the form of Poisson spike trains and the ECM, which is modeled by a
      phenomenological variable involved in two feedback mechanisms. One feedback
      mechanism scales the values of the input synaptic conductance to compensate for
      changes in firing rate. The second feedback accounts for slow fluctuations of the
      excitation threshold and depends on the ECM concentration. We show that the ECM
      mediated feedback acts as a robust mechanism to provide a homeostatic adjustment
      of the average firing rate. Interestingly, the activation of feedback mechanisms
      may lead to a bistability in which two different stable levels of average firing
      rates can coexist in a spiking network. We discuss the mechanisms of the
      bistability and how they may be related to memory function.

PMID- 22848556
TI  - Monitoring of human cytomegalovirus and virus-specific T-cell response in young
      patients receiving allogeneic hematopoietic stem cell transplantation.
AB  - In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, outcome
      of human cytomegalovirus (HCMV) infection results from balance between viral
      load/replication and pathogen-specific T-cell response. Using a cut-off of 30,000
      HCMV DNA copies/ml blood for pre-emptive therapy and cut-offs of 1 and 3 virus
      specific CD4(+) and CD8(+) T cells/ul blood for T-cell protection, we conducted
      in 131 young patients a prospective 3-year study aimed at verifying whether
      achievement of such immunological cut-offs protects from HCMV disease. In the
      first three months after transplantation, 55/89 (62%) HCMV-seropositive patients
      had infection and 36/55 (65%) were treated pre-emptively, whereas only 7/42 (17%)
      HCMV-seronegative patients developed infection and 3/7 (43%) were treated. After
      12 months, 76 HCMV-seropositive and 9 HCMV-seronegative patients (cumulative
      incidence: 90% and 21%, respectively) displayed protective HCMV-specific
      immunity. Eighty of these 85 (95%) patients showed spontaneous control of HCMV
      infection without additional treatment. Five patients after reaching protective T
      cell levels needed pre-emptive therapy, because they developed graft-versus-host
      disease (GvHD). HSCT recipients reconstituting protective levels of HCMV-specific
      T-cells in the absence of GvHD are no longer at risk for HCMV disease, at least
      within 3 years after transplantation. The decision to treat HCMV infection in
      young HSCT recipients may be taken by combining virological and immunological
      findings.

PMID- 22848557
TI  - Adenovirus-36 is associated with obesity in children and adults in Sweden as
      determined by rapid ELISA.
AB  - BACKGROUND: Experimental and natural human adenovirus-36 (Adv36) infection of
      multiple animal species results in obesity through increasing adipogenesis and
      lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum
      neutralization assay has previously been associated with obesity in children and
      adults living in the USA, South Korea and Italy, whereas no association with
      adult obesity was detected in Belgium/The Netherlands nor among USA military
      personnel. Adv36 infection has also been shown to reduce blood lipid levels,
      increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to
      associate with improved glycemic control in non-diabetic individuals. PRINCIPAL
      FINDINGS: Using a novel ELISA, 1946 clinically well-characterized individuals
      including 424 children and 1522 non-diabetic adults, and 89 anonymous blood
      donors, residing in central Sweden representing the population in Stockholm area,
      were studied for the presence of antibodies against Adv36 in serum. The
      prevalence of Adv36 positivity in lean individuals increased from ~7% in 1992
      1998 to 15-20% in 2002-2009, which paralleled the increase in obesity prevalence.
      We found that Adv36-positive serology was associated with pediatric obesity and
      with severe obesity in females compared to lean and overweight/mildly obese
      individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover,
      Adv36 positivity was less common among females and males on antilipid
      pharmacological treatment or with high blood triglyceride level. Insulin
      sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36
      positive obese females and males, although it was not statistically significant
      (p = 0.08). CONCLUSION: Using a novel ELISA we show that Adv36 infection is
      associated with pediatric obesity, severe obesity in adult females and lower risk
      of high blood lipid levels in non-diabetic Swedish individuals.

PMID- 22848558
TI  - Hypobaric intermittent hypoxia attenuates hypoxia-induced depressor response.
AB  - BACKGROUND: Hypobaric intermittent hypoxia (HIH) produces many favorable effects
      in the cardiovascular system such as anti-hypertensive effect. In this study, we
      showed that HIH significantly attenuated a depressor response induced by acute
      hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley rats received HIH in a
      hypobaric chamber simulating an altitude of 5000 m. The artery blood pressure
      (ABP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded
      in anesthetized control rats and rats received HIH. The baseline ABP, HR and RSNA
      were not different between HIH and control rats. Acute hypoxia-induced decrease
      in ABP was significantly attenuated in HIH rat compared with control rats.
      However, acute hypoxia-induced increases in HR and RSNA were greater in HIH rat
      than in control rats. After removal of bilateral ascending depressor nerves,
      acute hypoxia-induced depressor and sympathoexcitatory responses were comparable
      in control and HIH rats. Furthermore, acute hypoxia-induced depressor and
      sympathoexcitatory responses did not differ between control and HIH groups after
      blocking ATP-dependent K(+) channels by glibenclamide. The baroreflex function
      evaluated by intravenous injection of phenylephrine and sodium nitroprusside was
      markedly augmented in HIH rats compared with control rats. The pressor and
      sympathoexcitatory responses evoked by intravenous injection of cyanide potassium
      were also significantly greater in HIH rats than in control rats.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest that HIH suppresses acute hypoxia
      induced depressor response through enhancement of baroreflex and chemoreflex
      function, which involves activation of ATP-dependent K(+) channels. This study
      provides new information and underlying mechanism on the beneficiary effect of
      HIH on maintaining cardiovascular homeostasis.

PMID- 22848559
TI  - Diffuse coevolution between two Epicephala species (Gracillariidae) and two
      Breynia species (Phyllanthaceae).
AB  - The diffuse coevolution between two moth species (Epicephala lativalvaris and E.
      mirivalvata) and two plant species (Breynia fruticosa and B. rostrata) is
      reported based on field observations and indoor experiments conducted in Hainan
      and Fujian, China. Study results showed that the two Epicephala species jointly
      pollinated the two Breynia species, which led to a unique obligate pollination
      mutualism of two-to-two species specificity. A single Epicephala larva
      exclusively fed on seeds of host plants and developed to maturity by consuming
      all six seeds of each fruit, whereas a fraction of intact fruits were left to
      ensure the reproduction of plants within the whole population. Larvae of the two
      Epicephala species are competitive for resources; the population of E.
      mirivalvata is much smaller than that of E. lativalvaris, which has resulted from
      the differences in the female ovipositor structures and oviposition mode. The
      life history of Epicephala species highly coincides with the phenology of Breynia
      plants, and different phenology of B. fruticosa resulted in the different life
      history of the two Epicephala species in Hainan and Fujian. The natural
      hybridization of two host plants, possibly induced by the alternate pollination
      of two Epicephala species, is briefly discussed.

PMID- 22848560
TI  - Proteomics of protein secretion by Aggregatibacter actinomycetemcomitans.
AB  - The extracellular proteome (secretome) of periodontitis-associated bacteria may
      constitute a major link between periodontitis and systemic diseases. To obtain an
      overview of the virulence potential of Aggregatibacter actinomycetemcomitans, an
      oral and systemic human pathogen implicated in aggressive periodontitis, we used
      a combined LC-MS/MS and bioinformatics approach to characterize the secretome and
      protein secretion pathways of the rough-colony serotype a strain D7S. LC-MS/MS
      revealed 179 proteins secreted during biofilm growth. Further to confirming the
      release of established virulence factors (e.g. cytolethal distending toxin [CDT],
      and leukotoxin [LtxA]), we identified additional putative virulence determinants
      in the secretome. These included DegQ, fHbp, LppC, Macrophage infectivity protein
      (MIP), NlpB, Pcp, PotD, TolB, and TolC. This finding indicates that the number of
      extracellular virulence-related proteins is much larger than previously
      demonstrated, which was also supported by in silico analysis of the strain D7S
      genome. Moreover, our LC-MS/MS and in silico data revealed that at least Type I,
      II, and V secretion are actively used to excrete proteins directly into the
      extracellular space, or via two-step pathways involving the Sec/Tat systems for
      transport across the inner membrane, and outer membrane factors, secretins and
      auto-transporters, respectively for delivery across the outer membrane. Taken
      together, our results provide a molecular basis for further elucidating the role
      of A. actinomycetemcomitans in periodontal and systemic diseases.

PMID- 22848561
TI  - Bisphenol A binds to the local anesthetic receptor site to block the human
      cardiac sodium channel.
AB  - Bisphenol A (BPA) has attracted considerable public attention as it leaches from
      plastic used in food containers, is detectable in human fluids and recent
      epidemiologic studies link BPA exposure with diseases including cardiovascular
      disorders. As heart-toxicity may derive from modified cardiac electrophysiology,
      we investigated the interaction between BPA and hNav1.5, the predominant voltage
      gated sodium channel subtype expressed in the human heart. Electrophysiology
      studies of heterologously-expressed hNav1.5 determined that BPA blocks the
      channel with a K(d) of 25.4+/-1.3 uM. By comparing the effects of BPA and the
      local anesthetic mexiletine on wild type hNav1.5 and the F1760A mutant, we
      demonstrate that both compounds share an overlapping binding site. With a key
      binding determinant thus identified, an homology model of hNav1.5 was generated
      based on the recently-reported crystal structure of the bacterial voltage-gated
      sodium channel NavAb. Docking predictions position both ligands in a cavity
      delimited by F1760 and contiguous with the DIII-IV pore fenestration. Steered
      molecular dynamics simulations used to assess routes of ligand ingress indicate
      that the DIII-IV pore fenestration is a viable access pathway. Therefore BPA
      block of the human heart sodium channel involves the local anesthetic receptor
      and both BPA and mexiletine may enter the closed-state pore via membrane-located
      side fenestrations.

PMID- 22848562
TI  - Induction of heme oxygenase-1 inhibits cell death in crotonaldehyde-stimulated
      HepG2 cells via the PKC-delta-p38-Nrf2 pathway.
AB  - BACKGROUND: Crotonaldehyde, an alpha, beta-unsaturated aldehyde present in
      cigarette smoke, is an environmental pollutant and a product of lipid
      peroxidation. It also produces adverse effects to humans and is considered as a
      risk factor for various diseases. Heme oxygenase-1 (HO-1) plays important roles
      in protecting cells against oxidative stress as a prime cellular defense
      mechanism. However, HO-1 may be associated with cell proliferation and resistance
      to apoptosis in cancer cells. The aim of this study was to examine the effects of
      HO-1 induction on cell survival in crotonaldehyde-stimulated human hepatocellular
      carcinoma (HepG2) cells. METHODS: To investigate the signaling pathway involved
      in crotonaldehyde-induced HO-1 expression, we compared levels of inhibition
      efficiency of specific inhibitors and specific small interfering RNAs (siRNAs) of
      several kinases. The cell-cycle and cell death was measured by FACS and terminal
      dUTP nick-end labeling (TUNEL) staining. RESULTS: Treatment with crotonaldehyde
      caused a significant increase in nuclear translocation of NF-E2 related factor
      (Nrf2). Treatment with inhibitors of the protein kinase C-delta (PKC-delta) and
      p38 pathways resulted in obvious blockage of crotonaldehyde-induced HO-1
      expression. Furthermore, treatment with HO-1 siRNA and the specific HO-1
      inhibitor zinc-protoporphyrin produced an increase in the G(0)/G(1) phase of the
      cell cycle in crotonaldehyde-stimulated HepG2 cells. CONCLUSIONS: Taken together,
      the results support an anti-apoptotic role for HO-1 in crotonaldehyde-stimulated
      human hepatocellular carcinoma cells and provide a mechanism by which induction
      of HO-1 expression via PKC-delta-p38 MAPK-Nrf2 pathway may promote tumor
      resistance to oxidative stress.

PMID- 22848563
TI  - Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian
      multiple sclerosis associated alleles.
AB  - Vitamin D response elements (VDREs) have been found in the promoter region of the
      MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D
      availability VDREs are incapable of inducing *15:01 expression allowing in early
      life autoreactive T-cells to escape central thymic deletion. The Italian island
      of Sardinia exhibits a very high frequency of MS and high solar radiation
      exposure. We test the contribution of VDREs analysing the promoter region of the
      MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated
      *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and
      112 healthy subjects). Sequencing of the DRB1 promoter region revealed a
      homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in
      heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous
      VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated
      and canonical VDREs was assessed for its potential to modulate levels of DRB1
      gene expression using an in vitro transactivation assay after stimulation with
      active vitamin D metabolite. Vitamin D failed to increase promoter activity of
      the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and
      *03:01 alleles carrying the canonical VDRE sequence showed significantly
      increased transcriptional activity. The ability of VDR to bind the mutant VDRE in
      the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE
      sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic
      mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added.
      Conversely, the Sardinian mutated VDRE sample showed very low affinity for the
      RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter
      region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in
      Sardinian patients.

PMID- 22848564
TI  - Pyridoxal 5'-phosphate is a slow tight binding inhibitor of E. coli pyridoxal
      kinase.
AB  - Pyridoxal 5'-phosphate (PLP) is a cofactor for dozens of B(6) requiring enzymes.
      PLP reacts with apo-B(6) enzymes by forming an aldimine linkage with the epsilon
      amino group of an active site lysine residue, thus yielding the catalytically
      active holo-B(6) enzyme. During protein turnover, the PLP is salvaged by first
      converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal
      kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since
      its reactive 4'-aldehyde moiety forms covalent adducts with other compounds and
      non-B(6) proteins containing thiol or amino groups. The regulation of PLP
      homeostasis in the cell is thus an important, yet unresolved issue. In this
      report, using site-directed mutagenesis, kinetic, spectroscopic and
      chromatographic studies we show that pyridoxal kinase from E. coli forms a
      complex with the product PLP to form an inactive enzyme complex. Evidence is
      presented that, in the inhibited complex, PLP has formed an aldimine bond with an
      active site lysine residue during catalytic turnover. The rate of dissociation of
      PLP from the complex is very slow, being only partially released after a 2-hour
      incubation with PLP phosphatase. Interestingly, the inactive pyridoxal kinase*PLP
      complex can be partially reactivated by transferring the tightly bound PLP to an
      apo-B(6) enzyme. These results open new perspectives on the mechanism of
      regulation and role of pyridoxal kinase in the Escherichia coli cell.

PMID- 22848565
TI  - Quantitative ex-vivo micro-computed tomographic imaging of blood vessels and
      necrotic regions within tumors.
AB  - Techniques for visualizing and quantifying the microvasculature of tumors are
      essential not only for studying angiogenic processes but also for monitoring the
      effects of anti-angiogenic treatments. Given the relatively limited information
      that can be gleaned from conventional 2-D histological analyses, there has been
      considerable interest in methods that enable the 3-D assessment of the
      vasculature. To this end, we employed a polymerizing intravascular contrast
      medium (Microfil) and micro-computed tomography (micro-CT) in combination with a
      maximal spheres direct 3-D analysis method to visualize and quantify ex-vivo
      vessel structural features, and to define regions of hypoperfusion within tumors
      that would be indicative of necrosis. Employing these techniques we quantified
      the effects of a vascular disrupting agent on the tumor vasculature. The methods
      described herein for quantifying whole tumor vascularity represent a significant
      advance in the 3-D study of tumor angiogenesis and evaluation of novel
      therapeutics, and will also find potential application in other fields where
      quantification of blood vessel structure and necrosis are important outcome
      parameters.

PMID- 22848566
TI  - Long-chain acylcarnitines regulate the hERG channel.
AB  - BACKGROUND AND PURPOSE: In some pathological conditions carnitine concentration
      is high while in others it is low. In both cases,cardiac arrhythmias can occur
      and lead to sudden cardiac death. It has been proposed that in ischaemia,
      acylcarnitine (acyl-CAR), but not carnitine, is involved in arrhythmias through
      modulation of ionic currents. We studied the effects of acyl-CARs on hERG,
      K(IR)2.1 and K(v)7.1/minK channels (channels responsible for I(KR), I(K1) and
      I(KS) respectively). EXPERIMENTAL APPROACH: HEK293 cells stably expressing hERG,
      K(IR)2.1 or Kv7.1/minK were studied using the patch clamp technique. Free
      carnitine (CAR) and acyl-CAR derivatives from medium- (C8 and C10) and long-chain
      (C16 and C18:1) fatty acids were applied intra- and extracellularly at different
      concentrations. For studies on hERG, C16 and C18:1 free fatty acid were also
      used. KEY RESULTS: Extracellular long-chain (LCAC), but not medium-chain, acyl
      CAR,induced an increase of I(hERG) amplitude associated with a dose-dependent
      speeding of deactivation kinetics. They had no effect on K(IR)2.1 or Kv7.1/minK
      currents.Computer simulations of these effects were consistent with changes in
      action potential profile. CONCLUSIONS AND APPLICATIONS: Extracellular LCAC
      tonically regulates I(hERG) amplitude and kinetics under physiological
      conditions. This modulation may contribute to the changes in action potential
      duration that precede cardiac arrhythmias in ischaemia, diabetes and primary
      systemic carnitine deficiency.

PMID- 22848567
TI  - Promoter-specific expression and imprint status of marsupial IGF2.
AB  - In mice and humans, IGF2 has multiple promoters to maintain its complex tissue-
      and developmental stage-specific imprinting and expression. IGF2 is also
      imprinted in marsupials, but little is known about its promoter region. In this
      study, three IGF2 transcripts were isolated from placental and liver samples of
      the tammar wallaby, Macropus eugenii. Each transcript contained a unique 5'
      untranslated region, orthologous to the non-coding exons derived from promoters
      P1-P3 in the human and mouse IGF2 locus. The expression of tammar IGF2 was
      predominantly from the P2 promoter, similar to humans. Expression of IGF2 was
      higher in pouch young than in the adult and imprinting was highly tissue and
      developmental-stage specific. Interestingly, while IGF2 was expressed throughout
      the placenta, imprinting seemed to be restricted to the vascular, trilaminar
      region. In addition, IGF2 was monoallelically expressed in the adult mammary
      gland while in the liver it switched from monoalleleic expression in the pouch
      young to biallelic in the adult. These data suggest a complex mode of IGF2
      regulation in marsupials as seen in eutherian mammals. The conservation of the
      IGF2 promoters suggests they originated before the divergence of marsupials and
      eutherians, and have been selectively maintained for at least 160 million years.

PMID- 22848568
TI  - New strategies for echocardiographic evaluation of left ventricular function in a
      mouse model of long-term myocardial infarction.
AB  - BACKGROUND: The aim of this article is to present an optimized acquisition and
      analysis protocol for the echocardiographic evaluation of left ventricle (LV)
      remodeling in a mouse model of myocardial infarction (MI). METHODOLOGY: 13 female
      DBA/2J mice underwent permanent occlusion of the left anterior descending (LAD)
      coronary artery leading to MI. Mice echocardiography was performed using a Vevo
      770 (Visualsonics, Canada) before infarction, and 7, 14, 30, 60, 90 and 120 days
      after LAD ligation. LV systolic function was evaluated using different
      parameters, including the fractional area change (FAC%) computed in four high
      temporal resolution B-mode short axis images taken at different ventricular
      levels, and in one parasternal long axis. Pulsed wave and tissue Doppler modes
      were used to evaluate the diastolic function and Tei Index for global cardiac
      function. The echocardiographic measurements of infarct size were validated
      histologically using collagen deposition labeled by Sirius red staining. All data
      was analyzed using Shapiro-Wilk and Student's t-tests. PRINCIPAL FINDINGS: Our
      results reveal LV dilation resulting in marked remodeling an severe systolic
      dysfunction, starting seven days after MI (LV internal apical diameter, basal =
      2.82+/-0.24, 7d = 3.49+/-0.42; p<0.001. End-diastolic area, basal = 18.98+/-1.81,
      7d = 22.04+/-2.11; p<0.001). A strong statistically significant negative
      correlation exists between the infarct size and long-axis FAC% (r = -0.946; R(2)
      = 0.90; p<0.05). Moreover, the measured Tei Index values confirmed significant
      post-infarction impairment of the global cardiac function (basal = 0.46+/-0.07,
      7d = 0.55+/-0.08, 14 d = 0.57+/-0.06, 30 d = 0.54+/-0.06, 60 d = 0.54+/-0.07, 90
      d = 0.57+/-0.08; p<0.01). CONCLUSIONS/SIGNIFICANCE: In summary, we have performed
      a complete characterization of LV post-infarction remodeling in a DBA/2J mouse
      model of MI, using parameters adapted to the particular characteristics of the
      model In the future, this well characterized model will be used in both
      investigative and pharmacological studies that require accurate quantitative
      monitoring of cardiac recovery after myocardial infarction.

PMID- 22848569
TI  - The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1
      CRF01_AE infection.
AB  - INTRODUCTION: The design of a globally effective vaccine rests on the
      identification of epitopes capable of eliciting effective cytotoxic T lymphocyte
      (CTL) responses across multiple HIV clades in different populations. This study
      aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or
      clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.
      MATERIALS AND METHODS: 14 peptides based on consensus HIV-1 CRF01_AE amino acid
      sequences were designed for use in IFN-gamma ELISpot assays and (51)Cr release
      assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders
      carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico
      epitope-HLA prediction was performed. RESULTS: 29/66 (43.9%) patients recognized
      at least one peptide. In total 79 responses were seen against all 14 peptides.
      28/79 (35.4%) of the responses were in patients with HLA alleles previously
      reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in
      individuals with HLA alleles previously reported to restrict epitopes of HIV
      clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not
      associated with HLA alleles previously known to restrict HIV epitopes. In silico
      epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%)
      were associated with HLA-C alleles. We further confirmed a novel HLA restriction
      of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by
      HLA-B*40:01 with a standard (51)Cr release assay. DISCUSSION: CTL recognition
      sites in HIV-1 Gag were similar among different clades but the HLA restriction
      differed in Thai patients. This disparity in HLA restriction along different
      populations illustrated the importance of clade- and population-specific HLA
      analysis prior to CTL vaccine design.

PMID- 22848570
TI  - Proteochemometric modeling of the bioactivity spectra of HIV-1 protease
      inhibitors by introducing protein-ligand interaction fingerprint.
AB  - HIV-1 protease is one of the main therapeutic targets in HIV. However, a major
      problem in treatment of HIV is the rapid emergence of drug-resistant strains. It
      should be particularly helpful to clinical therapy of AIDS if one method can be
      used to predict antivirus capability of compounds for different variants. In our
      study, proteochemometric (PCM) models were created to study the bioactivity
      spectra of 92 chemical compounds with 47 unique HIV-1 protease variants. In
      contrast to other PCM models, which used Multiplication of Ligands and Proteins
      Descriptors (MLPD) as cross-term, one new cross-term, i.e. Protein-Ligand
      Interaction Fingerprint (PLIF) was introduced in our modeling. With different
      combinations of ligand descriptors, protein descriptors and cross-terms, nine PCM
      models were obtained, and six of them achieved good predictive abilities
      (Q(2)(test)>0.7). These results showed that the performance of PCM models could
      be improved when ligand and protein descriptors were complemented by the newly
      introduced cross-term PLIF. Compared with the conventional cross-term MLPD, the
      newly introduced PLIF had a better predictive ability. Furthermore, our best
      model (GD & P & PLIF: Q(2)(test) = 0.8271) could select out those inhibitors
      which have a broad antiviral activity. As a conclusion, our study indicates that
      proteochemometric modeling with PLIF as cross-term is a potential useful way to
      solve the HIV-1 drug-resistant problem.

PMID- 22848571
TI  - Incidence and predictors of adolescent's early sexual debut after three decades
      of HIV interventions in Tanzania: a time to debut analysis.
AB  - PURPOSE: To determine the incidence and predictors of adolescent's early sexual
      debut after three decades of HIV interventions in Tanzania. METHODS: In a cross
      section study of adolescents aged 16-19 residing in Morogoro Municipality,
      information on socio-demographic, parental-and-peer communication, and sexual
      behaviors were collected. Cox-regression analysis was used to examine predictors
      of time to sexual debut. RESULTS: A total of 316 adolescents with mean age of
      17.5+/-0.9 were recruited. Half (48.7%) of adolescent were sexually active with
      mean age at sexual debut of 14.6+/-2.3. Of these, 57.8% had sex before their
      15(th) birthday with incidence of early sexual debut of 17.4/1000 person-years at
      risk. Adolescent family characteristics, peer pressure, alcohol use, parental and
      peer communication were key predictors of early sexual debut. CONCLUSION:
      Parental and peer communication strategies works calling for efforts to increase
      its scope to reach all adolescents alongside promoting family stability and
      reducing adolescent alcohol consumption.

PMID- 22848572
TI  - Development of a novel in silico docking simulation model for the fine HIV-1
      cytotoxic T lymphocyte epitope mapping.
AB  - INTRODUCTION: Class I HLA's polymorphism has hampered CTL epitope mapping with
      laborious experiments. Objectives are 1) to evaluate the novel in silico model in
      predicting previously reported epitopes in comparison with existing program, and
      2) to apply the model to predict optimal epitopes with HLA using experimental
      results. MATERIALS AND METHODS: We have developed a novel in silico epitope
      prediction method, based on HLA crystal structure and a peptide docking
      simulation model, calculating the peptide-HLA binding affinity at four amino acid
      residues in each terminal. It was applied to predict 52 HIV best-defined CTL
      epitopes from 15-mer overlapping peptides, and its predictive ability was
      compared with the HLA binding motif-based program of HLArestrictor. It was then
      used to predict HIV-1 Gag optimal epitopes from previous ELISpot results.
      RESULTS: 43/52 (82.7%) epitopes were detected by the novel model, whereas 37
      (71.2%) by HLArestrictor. We also found a significant reduction in epitope
      detection rates for longer epitopes in HLArestrictor (p = 0.027), but not in the
      novel model. Improved epitope prediction was also found by introducing both
      models, especially in specificity (p<0.001). Eight peptides were predicted as
      novel, immunodominant epitopes in both models. DISCUSSION: This novel model can
      predict optimal CTL epitopes, which were not detected by an existing program.
      This model is potentially useful not only for narrowing down optimal epitopes,
      but predicting rare HLA alleles with less information. By introducing different
      principal models, epitope prediction will be more precise.

PMID- 22848573
TI  - Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor
      density in cultured pregnant human myometrial smooth muscle cells.
AB  - Epidemiological studies and interventional clinical trials indicate that
      consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as
      docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms
      are not well understood, prostaglandins (PG) of the 2-series are known to play a
      role in the initiation and progress of labor. In animal studies, modest DHA
      provision has been shown to reduce placental and uterine PGE(2) and PGF(2alpha),
      matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase
      activity. However, modulation of PG biosynthesis may not account for all the
      effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent
      mechanism of LC PUFA action using cultured pregnant human myometrial smooth
      muscle cells. Our goal was to characterize the effect of LC PUFA treatment on
      oxytocin signaling, a potent uterotonic hormone involved in labor. The addition
      of 10 uM-100 uM DHA or arachidonic acid (AA) to the culture media for 48 h
      resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA
      and AA significantly inhibited phosphatidylinositol turnover and [Ca(2+)](i)
      mobilization with oxytocin stimulation compared to bovine serum albumin control
      and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor
      membrane concentration without altering binding affinity or rate of receptor
      internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation
      of oxytocin signaling and provide new insight into additional mechanisms
      pertaining to reports of dietary fish and fish oil consumption prolonging
      gestation.

PMID- 22848574
TI  - Viral reverse transcriptases show selective high affinity binding to DNA-DNA
      primer-templates that resemble the polypurine tract.
AB  - Previous results using a SELEX (Systematic Evolution of Ligands by Exponential
      Enrichment)-based approach that selected DNA primer-template duplexes binding
      with high affinity to HIV reverse transcriptase (RT) showed that primers
      mimicking the 3' end, and in particular the six nt terminal G tract, of the RNA
      polypurine tract (PPT; HIV PPT: 5'-AAAAGAAAAGGGGGG-3') were preferentially
      selected. In this report, two viral (Moloney murine leukemia virus (MuLV) and
      avian myeloblastosis virus (AMV)) and one retrotransposon (Ty3) RTs were used for
      selection. Like HIV RT, both viral RTs selected duplexes with primer strands
      mimicking the G tract at the PPT 3' end (AMV PPT: 5'-AGGGAGGGGGA-3'; MuLV PPT: 5'
      AGAAAAAGGGGGG-3'). In contrast, Ty3, whose PPT lacks a G tract (5'-GAGAGAGAGGAA
      3') showed no selective binding to any duplex sequences. Experiments were also
      conducted with DNA duplexes (termed DNA PPTs) mimicking the RNA PPT-DNA duplex of
      each virus and a control duplex with a random DNA sequence. Retroviral RTs bound
      with high affinity to all viral DNA PPT constructs, with HIV and MuLV RTs showing
      comparable binding to the counterpart DNA PPT duplexes and reduced affinity to
      the AMV DNA PPT. AMV RT showed similar behavior with a modest preference for its
      own DNA PPT. Ty3 RT showed no preferential binding for its own or any other DNA
      PPT and viral RTs bound the Ty3 DNA PPT with relatively low affinity. In
      contrast, binding affinity of HIV RT to duplexes containing the HIV RNA PPT was
      less dependent on the G tract, which is known to be pivotal for efficient
      extension. We hypothesize that the G tract on the RNA PPT helps shift the binding
      orientation of RT to the 3' end of the PPT where extension can occur.

PMID- 22848575
TI  - Ocean acidification refugia of the Florida Reef Tract.
AB  - Ocean acidification (OA) is expected to reduce the calcification rates of marine
      organisms, yet we have little understanding of how OA will manifest within
      dynamic, real-world systems. Natural CO(2), alkalinity, and salinity gradients
      can significantly alter local carbonate chemistry, and thereby create a range of
      susceptibility for different ecosystems to OA. As such, there is a need to
      characterize this natural variability of seawater carbonate chemistry, especially
      within coastal ecosystems. Since 2009, carbonate chemistry data have been
      collected on the Florida Reef Tract (FRT). During periods of heightened
      productivity, there is a net uptake of total CO(2) (TCO(2)) which increases
      aragonite saturation state (Omega(arag)) values on inshore patch reefs of the
      upper FRT. These waters can exhibit greater Omega(arag) than what has been
      modeled for the tropical surface ocean during preindustrial times, with mean (+/-
      std. error) Omega(arag)-values in spring = 4.69 (+/-0.101). Conversely,
      Omega(arag)-values on offshore reefs generally represent oceanic carbonate
      chemistries consistent with present day tropical surface ocean conditions. This
      gradient is opposite from what has been reported for other reef environments. We
      hypothesize this pattern is caused by the photosynthetic uptake of TCO(2) mainly
      by seagrasses and, to a lesser extent, macroalgae in the inshore waters of the
      FRT. These inshore reef habitats are therefore potential acidification refugia
      that are defined not only in a spatial sense, but also in time; coinciding with
      seasonal productivity dynamics. Coral reefs located within or immediately
      downstream of seagrass beds may find refuge from OA.

PMID- 22848576
TI  - Low-dose alcohol consumption protects against transient focal cerebral ischemia
      in mice: possible role of PPARgamma.
AB  - BACKGROUND: We examined the influence of low-dose alcohol consumption on cerebral
      ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying
      the neuroprotective effect of low-dose alcohol consumption. METHODOLOGY/PRINCIPAL
      FINDINGS: C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8
      weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome
      proliferator-activated receptor gamma (PPARgamma)-selective agonist, or GW9662 (3
      mg/kg/day), a selective PPARgamma antagonist, for 2 weeks. The mice were
      subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes.
      Brain injury, DNA fragmentation and nuclear PPARgamma protein/activity were
      evaluated at 24 hours of reperfusion. We found that the brain injury and DNA
      fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed
      mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but
      didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened
      the brain injury in alcohol-fed mice, but didn't alter the brain injury in
      nonalcohol-fed mice. Nuclear PPARgamma protein/activity at peri-infarct and the
      contralateral corresponding areas of the parietal cortex was greater in alcohol
      fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic
      (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure
      on nuclear PPARgamma protein/activity and the influence of low-dose alcohol
      exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced
      apoptosis. We found that low-dose alcohol exposure increased nuclear PPARgamma
      protein/activity and protected against the OGD/reoxygenation-induced apoptosis.
      The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced
      apoptosis was abolished by GW9662. CONCLUSIONS/SIGNIFICANCE: Our findings suggest
      that chronic consumption of low-dose alcohol protects the brain against I/R
      injury. The neuroprotective effect of low-dose alcohol consumption may be related
      to an upregulated PPARgamma.

PMID- 22848577
TI  - Elucidation of xenobiotic metabolism pathways in human skin and human skin models
      by proteomic profiling.
AB  - BACKGROUND: Human skin has the capacity to metabolise foreign chemicals
      (xenobiotics), but knowledge of the various enzymes involved is incomplete. A
      broad-based unbiased proteomics approach was used to describe the profile of
      xenobiotic metabolising enzymes present in human skin and hence indicate
      principal routes of metabolism of xenobiotic compounds. Several in vitro models
      of human skin have been developed for the purpose of safety assessment of
      chemicals. The suitability of these epidermal models for studies involving
      biotransformation was assessed by comparing their profiles of xenobiotic
      metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS:
      Label-free proteomic analysis of whole human skin (10 donors) was applied and
      analysed using custom-built PROTSIFT software. The results showed the presence of
      enzymes with a capacity for the metabolism of alcohols through dehydrogenation,
      aldehydes through dehydrogenation and oxidation, amines through oxidation,
      carbonyls through reduction, epoxides and carboxylesters through hydrolysis and,
      of many compounds, by conjugation to glutathione. Whereas protein levels of these
      enzymes in skin were mostly just 4-10 fold lower than those in liver and
      sufficient to support metabolism, the levels of cytochrome P450 enzymes were at
      least 300-fold lower indicating they play no significant role. Four epidermal
      models of human skin had profiles very similar to one another and these
      overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The
      proteomics profiling approach was successful in producing a comprehensive
      analysis of the biotransformation characteristics of whole human skin and various
      in vitro skin models. The results show that skin contains a range of defined
      enzymes capable of metabolising different classes of chemicals. The degree of
      similarity of the profiles of the in vitro models indicates their suitability for
      epidermal toxicity testing. Overall, these results provide a rational basis for
      explaining the fate of xenobiotics in skin and will aid chemical safety testing
      programmes.

PMID- 22848578
TI  - Investigating the production of foreign membrane proteins in tobacco
      chloroplasts: expression of an algal plastid terminal oxidase.
AB  - Chloroplast transformation provides an inexpensive, easily scalable production
      platform for expression of recombinant proteins in plants. However, this
      technology has been largely limited to the production of soluble proteins. Here
      we have tested the ability of tobacco chloroplasts to express a membrane protein,
      namely plastid terminal oxidase 1 from the green alga Chlamydomonas reinhardtii
      (Cr-PTOX1), which is predicted to function as a plastoquinol oxidase. A
      homoplastomic plant containing a codon-optimised version of the nuclear gene
      encoding PTOX1, driven by the 16S rRNA promoter and 5'UTR of gene 10 from phage
      T7, was generated using a particle delivery system. Accumulation of Cr-PTOX1 was
      shown by immunoblotting and expression in an enzymatically active form was
      confirmed by using chlorophyll fluorescence to measure changes in the redox state
      of the plastoquinone pool in leaves. Growth of Cr-PTOX1 expressing plants was,
      however, more sensitive to high light than WT. Overall our results confirm the
      feasibility of using plastid transformation as a means of expressing foreign
      membrane proteins in the chloroplast.

PMID- 22848579
TI  - Photoperiodic influences on ultradian rhythms of male Siberian hamsters.
AB  - Seasonal changes in mammalian physiology and behavior are proximately controlled
      by the annual variation in day length. Long summer and short winter day lengths
      markedly alter the amplitude of endogenous circadian rhythms and may affect
      ultradian oscillations, but the threshold photoperiods for inducing these changes
      are not known. We assessed the effects of short and intermediate day lengths and
      changes in reproductive physiology on circadian and ultradian rhythms of
      locomotor activity in Siberian hamsters. Males were maintained in a long
      photoperiod from birth (15 h light/day; 15 L) and transferred in adulthood to 1
      of 7 experimental photoperiods ranging from 14 L to 9 L. Decreases in circadian
      rhythm (CR) robustness, mesor and amplitude were evident in photoperiods <=14 L,
      as were delays in the timing of CR acrophase and expansion of nocturnal activity
      duration. Nocturnal ultradian rhythms (URs) were comparably prevalent in all day
      lengths, but 15 L markedly inhibited the expression of light-phase URs. The
      period (tau'), amplitude and complexity of URs increased in day lengths <=13 L.
      Among hamsters that failed to undergo gonadal regression in short day lengths
      (nonresponders), tau' of the dark-phase UR was longer than in photoresponsive
      hamsters; in 13 L the incidence and amplitude of light-phase URs were greater in
      hamsters that did not undergo testicular regression. Day lengths as long as 14 L
      were sufficient to trigger changes in the waveform of CRs without affecting UR
      waveform. The transition from a long- to a short-day ultradian phenotype occurred
      for most UR components at day lengths of 12 L-13 L, thereby establishing
      different thresholds for CR and UR responses to day length. At the UR-threshold
      photoperiod of 13 L, differences in gonadal status were largely without effect on
      most UR parameters.

PMID- 22848582
TI  - Pest-suppression potential of midwestern landscapes under contrasting bioenergy
      scenarios.
AB  - Biomass crops grown on marginal soils are expected to fuel an emerging bioenergy
      industry in the United States. Bioenergy crop choice and position in the
      landscape could have important impacts on a range of ecosystem services,
      including natural pest-suppression (biocontrol services) provided by predatory
      arthropods. In this study we use predation rates of three sentinel crop pests to
      develop a biocontrol index (BCI) summarizing pest-suppression potential in corn
      and perennial grass-based bioenergy crops in southern Wisconsin, lower Michigan,
      and northern Illinois. We show that BCI is higher in perennial grasslands than in
      corn, and increases with the amount of perennial grassland in the surrounding
      landscape. We develop an empirical model for predicting BCI from information on
      energy crop and landscape characteristics, and use the model in a qualitative
      assessment of changes in biocontrol services for annual croplands on prime
      agricultural soils under two contrasting bioenergy scenarios. Our analysis
      suggests that the expansion of annual energy crops onto 1.2 million ha of
      existing perennial grasslands on marginal soils could reduce BCI between -10 and 
      64% for nearly half of the annual cropland in the region. In contrast,
      replacement of the 1.1 million ha of existing annual crops on marginal land with
      perennial energy crops could increase BCI by 13 to 205% on over half of the
      annual cropland in the region. Through comparisons with other independent
      studies, we find that our biocontrol index is negatively related to insecticide
      use across the Midwest, suggesting that strategically positioned, perennial
      bioenergy crops could reduce insect damage and insecticide use on neighboring
      food and forage crops. We suggest that properly validated environmental indices
      can be used in decision support systems to facilitate integrated assessments of
      the environmental and economic impacts of different bioenergy policies.

PMID- 22848580
TI  - Burkholderia cenocepacia type VI secretion system mediates escape of type II
      secreted proteins into the cytoplasm of infected macrophages.
AB  - Burkholderia cenocepacia is an opportunistic pathogen that survives
      intracellularly in macrophages and causes serious respiratory infections in
      patients with cystic fibrosis. We have previously shown that bacterial survival
      occurs in bacteria-containing membrane vacuoles (BcCVs) resembling arrested
      autophagosomes. Intracellular bacteria stimulate IL-1beta secretion in a caspase
      1-dependent manner and induce dramatic changes to the actin cytoskeleton and the
      assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion
      system (T6SS) is required for these phenotypes but surprisingly it is not
      required for the maturation arrest of the BcCV. Here, we show that macrophages
      infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1beta
      secretion and pyroptosis. Moreover, IL-1beta secretion by B. cenocepacia-infected
      macrophages is suppressed in deletion mutants unable to produce functional Type
      VI, Type IV, and Type 2 secretion systems (SS). We provide evidence that the T6SS
      mediates the disruption of the BcCV membrane, which allows the escape of proteins
      secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the
      activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and
      ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for
      efficient IL-1beta secretion in a T6SS dependent manner. ZmpA and ZmpB are also
      required for the maturation arrest of the BcCVs and bacterial intra-macrophage
      survival in a T6SS-independent fashion. Our results uncover a novel mechanism for
      inflammasome activation that involves cooperation between two bacterial secretory
      pathways, and an unanticipated role for T2SS-secreted proteins in intracellular
      bacterial survival.

PMID- 22848581
TI  - Assessment of roles for calreticulin in the cross-presentation of soluble and
      bead-associated antigens.
AB  - Antigen cross-presentation involves the uptake and processing of exogenously
      derived antigens and their assembly with major histocompatibility complex (MHC)
      class I molecules. Antigen presenting cells (APC) load peptides derived from the
      exogenous antigens onto MHC class I molecules for presentation to CD8 T cells.
      Calreticulin has been suggested to mediate and enhance antigen cross-presentation
      of soluble and cell-derived antigens. In this study, we examined roles for
      calreticulin in cross-presentation of ovalbumin using a number of models. Our
      findings indicate that calreticulin does not enhance in vitro cross-presentation
      of an ovalbumin-derived peptide, or of fused or bead-associated ovalbumin.
      Additionally, in vivo, calreticulin fusion or co-conjugation does not enhance the
      efficiency of CD8 T cell activation by soluble or bead-associated ovalbumin
      either in wild type mice or in mice lacking Toll-like receptor 4 (TLR4).
      Furthermore, we detect no significant differences in cross-presentation
      efficiencies of glycosylated vs. non-glycosylated forms of ovalbumin. Together,
      these results point to the redundancies in pathways for uptake of soluble and
      bead-associated antigens.

PMID- 22848583
TI  - Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: a
      comparative study of experiments in silico and with cells.
AB  - Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of
      drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid
      bilayers predicted the existence of three regimes of action of DMSO: membrane
      loosening, pore formation and bilayer collapse. We show here that these modes of
      action are also reproduced in the presence of cholesterol in the bilayer, and we
      provide a description at the atomic detail of the DMSO-mediated process of pore
      formation in cholesterol-containing lipid membranes. We also successfully explore
      the applicability of DMSO to promote plasma membrane permeability to water,
      calcium ions (Ca(2+)) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes.
      The experimental results on cells in culture can be easily explained according to
      the three expected regimes: in the presence of low doses of DMSO, the membrane of
      the cells exhibits undulations but no permeability increase can be detected,
      while at intermediate DMSO concentrations cells are permeabilized to water and
      calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be
      associated to the MD-predicted consequences of the effects of the DMSO at low and
      intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization
      is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced
      membrane-destructuring effects described in the MD simulations.

PMID- 22848584
TI  - Psyllium supplementation in adolescents improves fat distribution & lipid
      profile: a randomized, participant-blinded, placebo-controlled, crossover trial.
AB  - AIMS: We aimed to assess the effects of psyllium supplementation on insulin
      sensitivity and other parameters of the metabolic syndrome in an at risk
      adolescent population. METHODS: This study encompassed a participant-blinded,
      randomized, placebo-controlled, crossover trial. Subjects were 47 healthy
      adolescent males aged 15-16 years, recruited from secondary schools in lower
      socio-economic areas with high rates of obesity. Participants received 6 g/day of
      psyllium or placebo for 6 weeks, with a two-week washout before crossing over.
      Fasting lipid profiles, ambulatory blood pressure, auxological data, body
      composition, activity levels, and three-day food records were collected at
      baseline and after each 6-week intervention. Insulin sensitivity was measured by
      the Matsuda method using glucose and insulin values from an oral glucose
      tolerance test. RESULTS: 45 subjects completed the study, and compliance was very
      high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of
      subjects were overweight or obese. 28% had decreased insulin sensitivity, but
      none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction
      in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%)
      reduction in LDL cholesterol (p = 0.042). No associated adverse events were
      recorded. CONCLUSIONS: Dietary supplementation with 6 g/day of psyllium over 6
      weeks improves fat distribution and lipid profile (parameters of the metabolic
      syndrome) in an at risk population of adolescent males. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry ACTRN12609000888268.

PMID- 22848586
TI  - Appearance matters: neural correlates of food choice and packaging aesthetics.
AB  - Neuro-imaging holds great potential for predicting choice behavior from brain
      responses. In this study we used both traditional mass-univariate and state-of
      the-art multivariate pattern analysis to establish which brain regions respond to
      preferred packages and to what extent neural activation patterns can predict
      realistic low-involvement consumer choices. More specifically, this was assessed
      in the context of package-induced binary food choices. Mass-univariate analyses
      showed that several regions, among which the bilateral striatum, were more
      strongly activated in response to preferred food packages. Food choices could be
      predicted with an accuracy of up to 61.2% by activation patterns in brain regions
      previously found to be involved in healthy food choices (superior frontal gyrus)
      and visual processing (middle occipital gyrus). In conclusion, this study shows
      that mass-univariate analysis can detect small package-induced differences in
      product preference and that MVPA can successfully predict realistic low
      involvement consumer choices from functional MRI data.

PMID- 22848585
TI  - Increased angiogenesis and improved left ventricular function after
      transplantation of myoblasts lacking the MyoD gene into infarcted myocardium.
AB  - Skeletal myoblast transplantation has therapeutic potential for repairing damaged
      heart. However, the optimal conditions for this transplantation are still
      unclear. Recently, we demonstrated that satellite cell-derived myoblasts lacking
      the MyoD gene (MyoD(-/-)), a master transcription factor for skeletal muscle
      myogenesis, display increased survival and engraftment compared to wild-type
      controls following transplantation into murine skeletal muscle. In this study, we
      compare cell survival between wild-type and MyoD(-/-) myoblasts after
      transplantation into infarcted heart. We demonstrate that MyoD(-/-) myoblasts
      display greater resistance to hypoxia, engraft with higher efficacy, and show a
      larger improvement in ejection fraction than wild-type controls. Following
      transplantation, the majority of MyoD(-/-) and wild-type myoblasts form skeletal
      muscle fibers while cardiomyocytes do not. Importantly, the transplantation of
      MyoD(-/-) myoblasts induces a high degree of angiogenesis in the area of injury.
      DNA microarray data demonstrate that paracrine angiogenic factors, such as
      stromal cell-derived factor-1 (SDF-1) and placental growth factor (PlGF), are up
      regulated in MyoD(-/-) myoblasts. In addition, over-expression and gene knockdown
      experiments demonstrate that MyoD negatively regulates gene expression of these
      angiogenic factors. These results indicate that MyoD(-/-) myoblasts impart
      beneficial effects after transplantation into an infarcted heart, potentially due
      to the secretion of paracrine angiogenic factors and enhanced angiogenesis in the
      area of injury. Therefore, our data provide evidence that a genetically
      engineered myoblast cell type with suppressed MyoD function is useful for
      therapeutic stem cell transplantation.

PMID- 22848587
TI  - Serum level of CC-chemokine ligand 18 is increased in patients with non-small
      cell lung cancer and correlates with survival time in adenocarcinomas.
AB  - CC-chemokine ligand 18 (CCL18) is mainly expressed by alternatively activated
      macrophages and DCs and plays an important role in lung fibrosis, arthritis and
      other diseases. Here CCL18 was measured in sera of 31 healthy volunteers and 170
      patients with lung cancer and correlated these data with histology, tumor stage
      and clinical parameters. Mean CCL18 serum level of the patients with non-small
      cell lung cancer was 150(857) ng/ml vs. 32(61) ng/ml in the healthy control
      group. Patient groups differ significantly according their histology
      (adenocarcinoma 143(528) ng/ml vs squamous cell carcinoma 187(857) ng/ml,
      p<0.02). In addition, we found a significant difference between patients with
      lower versus higher T-stage (p<0.003). Receiver operating characteristic (ROC)
      analyses revealed a cutoff point of 83 ng/ml (area under the curve (AUC): 0.968;
      p<0.0001) to discriminate between healthy controls and non-small-cell lung cancer
      patients. ROC analyses to discriminate between patients, who died because of
      cancer related death and those who died for other reasons did not lead to a valid
      AUC. To stratify the tumor patients, a criterion value plot was performed leading
      to a point of equal sensitivity and specificity (54%) of 162 ng/ml. Patients with
      a CCL18 serum level higher than 160 ng/ml had a mean survival time of 623 days.
      In contrast, those in patients with a baseline level between 83 ng/ml and 160
      ng/ml the mean survival time was 984 days (p<0.005). Survival-analysis revealed
      in adenocarcinoma a mean survival of 1152 days in the group below 83 ng/ml. In
      the median group the mean survival time was 788 days and in the group with the
      highest levels the mean survival time was 388 days (p<0.001). In contrast, we
      found no correlation between the FEV1 and the CCL18 baseline level. In
      conclusion, in patients suffering from adenocarcinoma increased serum CCL18
      levels predict a diminished survival time.

PMID- 22848588
TI  - A BCAM0223 mutant of Burkholderia cenocepacia is deficient in hemagglutination,
      serum resistance, adhesion to epithelial cells and virulence.
AB  - Burkholderia cepacia complex (Bcc) bacteria are a problematic group of
      microorganisms causing severe infections in patients with Cystic Fibrosis. In
      early stages of infection, Bcc bacteria must be able to adhere to and colonize
      the respiratory epithelium. Although this is not fully understood, this primary
      stage of infection is believed to be in part mediated by a specific type of
      adhesins, named trimeric autotransporter adhesins (TAAs). These homotrimeric
      proteins exist on the surface of many gram negative pathogens and often mediate a
      number of critical functions, including biofilm formation, serum resistance and
      adherence to an invasion of host cells. We have previously identified in the
      genome of the epidemic clinical isolate B. cenocepacia J2315, a novel cluster of
      genes putatively encoding three TAAs (BCAM0219, BCAM0223 and BCAM0224). In this
      study, the genomic organization of the TAA cluster has been determined. To
      further address the direct role of the putative TAA BCAM0223 in B. cenocepacia
      pathogenicity, an isogenic mutant was constructed via insertional inactivation.
      The BCAM0223::Tp mutant is deficient in hemagglutination, affected in adherence
      to vitronectin and in biofilm formation and showed attenuated virulence in the
      Galleria mellonella model of infection. Moreover, the BCAM0223::Tp mutant also
      showed a significant reduction in its resistance to human serum as well as in
      adherence, but not in invasion of, cultured human bronchial epithelial cells.
      Altogether these results demonstrate that the BCAM0223 protein is a
      multifunctional virulence factor that may contribute to the pathogenicity of B.
      cenocepacia.

PMID- 22848589
TI  - Diversity and relationships of eggplants from three geographically distant
      secondary centers of diversity.
AB  - Eggplant (Solanum melongena L.) was domesticated in the Indo-Birmanian region,
      which is also the primary center of diversity for this crop. From there eggplant
      spread to other regions, and diversity accumulated in several secondary centers
      of diversity. We have assessed the diversity and relationships of 52 accessions
      of eggplant from three geographically distant secondary centers of diversity
      (China, Spain, and Sri Lanka) using 28 morphological descriptors and 12 highly
      polymorphic genomic SSRs. A wide variation was found for most morphological
      traits, and significant differences among the three centers of diversity were
      detected for 22 of these traits. The PCA analysis showed that eggplants from the
      three origins were morphologically differentiated, and accessions from each of
      the three secondary centers of diversity presented a typical combination of
      morphological characteristics. In this respect, discriminant analysis showed that
      accessions could be correctly classified to their origin using only six traits.
      The SSR characterization identified 110 alleles and allowed obtaining a unique
      genetic fingerprint for each accession. Many alleles were found to be private to
      each origin, but no universal alleles were found for any of the origins. The PCA
      analysis showed that the genetic differentiation among origins was less clear
      than for morphological traits, although the analysis of the population structure
      shows that accessions mostly group according to the origin, but also provides
      evidence of migration among the three secondary centers of diversity. The genetic
      diversity (H(T)) within each origin was high, ranging between H(T) = 0.5400 (Sri
      Lanka) and H(T) = 0.4943 (China), while the standardized genetic differentiation
      (G'(ST)) among origins was moderate (G'(ST) = 0.2657). The correlation between
      morphological and SSR distances was non-significant (r = 0.044), indicating that
      both data are complementary for the conservation of germplasm and breeding of
      eggplant. These results are relevant for the management of genetic resources,
      breeding programmes, and evolutionary studies of eggplant.

PMID- 22848590
TI  - One species, three Pleistocene evolutionary histories: phylogeography of the
      Italian crested newt, Triturus carnifex.
AB  - Phylogeographic patterns of temperate species from the Mediterranean peninsulas
      have been investigated intensively. Nevertheless, as more phylogeographies become
      available, either unique patterns or new lines of concordance continue to emerge,
      providing new insights on the evolution of regional biotas. Here, we investigated
      the phylogeography and evolutionary history of the Italian crested newt, Triturus
      carnifex, through phylogenetic, molecular dating and population structure
      analyses of two mitochondrial gene fragments (ND2 and ND4; overall 1273 bp). We
      found three main mtDNA lineages having parapatric distribution and estimated
      divergence times between Late Pliocene and Early Pleistocene. One lineage (S) was
      widespread south of the northern Apennine chain and was further geographically
      structured into five sublineages, likely of Middle Pleistocene origin. The second
      lineage (C) was widespread throughout the Padano-Venetian plain and did not show
      a clear phylogeographic structure. The third lineage (N) was observed in only two
      populations located on western Croatia/Slovenia. Results of analysis of molecular
      variance suggested that partitioning populations according to the geographic
      distribution of these lineages and sublineages explains 76% of the observed
      genetic variation. The phylogeographic structure observed within T. carnifex and
      divergence time estimates among its lineages, suggest that responses to
      Pleistocene environmental changes in this single species have been as diverse as
      those found previously among several codistributed temperate species combined.
      Consistent with the landscape heterogeneity, physiographic features, and
      palaeogeographical evolution of its distribution range, these responses encompass
      multiple refugia along the Apennine chain, lowland refugia in large peri-coastal
      plains, and a 'cryptic' northern refugium.

PMID- 22848591
TI  - PDHK-2 deficiency is associated with attenuation of lipase-mediated fat
      consumption for the increased survival of Caenorhabditis elegans dauers.
AB  - In Caenorhabditis elegans, slow fat consumption has been suggested to contribute
      to the extension of the survival rate during nutritionally adverse conditions.
      Here, we investigated the potential role of pyruvate dehydrogenase kinase (PDHK)
      2, the C. elegans homolog of mammalian PDK, effects on fat metabolism under
      nutritional conditions. PDHK-2 was expressed at low levels under well-fed
      conditions but was highly induced during long-term starvation and in the dauer
      state. This increase in pdhk-2 expression was regulated by both DAF-16 and NHR
      49. Dauer-specific induction of PDHK-2 was abolished upon entry into the post
      dauer stage. Interestingly, in the long-term dauer state, stored fat levels were
      higher in daf-2(e1370);pdhk-2 double mutants than in daf-2(e1370), suggesting a
      positive relationship between PDHK-2 activity and fat consumption. PDHK-2
      deficiency has been shown to lead to greater preservation of residual fats, which
      would be predicted to contribute to survival during the dauer state. A test of
      this prediction showed that the survival rates of daf-2(e1370);pdhk-2(tm3075) and
      daf-2(e1370);pdhk-2(tm3086) double mutants were higher than that of daf-2(e1370),
      suggesting that loss of either the ATP-binding domain (tm3075) or branched chain
      keto-acid dehydrogenase kinase domain (tm3086) of PDHK-2 leads to reduced fat
      consumption and thus favors increased dauer survival. This attenuated fat
      consumption in the long-term dauer state of C. elegans daf-2 (e1370);pdhk-2
      mutants was associated with concomitant down-regulation of the lipases ATGL
      (adipose triglyceride lipase), HSL (hormone-sensitive lipase), and C07E3.9
      (phospholipase). In contrast, PDHK-2 overexpression in wild-type starved worms
      induced lipase expression and promoted abnormal dauer formation. Thus, we propose
      that PDHK-2 serves as a molecular bridge, connecting fat metabolism and survival
      under nutritionally adverse conditions in C. elegans.

PMID- 22848592
TI  - Acute pain therapy in postanesthesia care unit directed by skin conductance: a
      randomized controlled trial.
AB  - BACKGROUND: After surgery, effective and well-directed acute pain therapy is a
      necessary and integral part of the overall treatment plan. Generally, the
      assessment of pain intensity depends on a patient's self-evaluation using scoring
      systems such as numeric rating scales (NRS, 0 to 10). Recently, a "Pain Monitor"
      was commercially provided which is based on measurements of fluctuations of skin
      conductance (NFSC). In this randomized, controlled, single-blind trial, possible
      benefits of this certain device were studied. METHODS: Postoperative patients (n
      = 44) were randomly assigned to a test or a control group during their stay in
      the postanesthesia care unit (PACU). All patients were treated and monitored
      according to internal hospital standards. Whereas all patients systematically
      evaluated their pain each 15 min, test group patients were additionally addressed
      when NFSC exceeded a predefined level. In cases of NRS>=5 during a routine
      elevation or in between, pain relief was achieved by standard procedures
      irrespective of group allocation. RESULTS: During their stay in PACU, both test
      and control groups experienced a significant decrease in NRS as a consequence of
      pain therapy. No significant differences in mean NRS or in NFSC values were found
      between the test and control groups. No correlation was observed between NRS and
      NFSC. CONCLUSION: Postoperative patients experience diverse stressors, such as
      anxiety, disorientation, shivering, sickness and pain. Although the application
      of continuous pain monitoring would be meaningful in this clinical setting, the
      tested device failed to distinguish pain from other stressors in postoperative
      adult patients. TRIAL REGISTRATION: German Clinical Trials Register DRKS00000755.

PMID- 22848593
TI  - Specificity responses of grasshoppers in temperate grasslands to diel asymmetric
      warming.
AB  - BACKGROUND: Global warming is characterized by not only an increase in the daily
      mean temperature, but also a diel asymmetric pattern. However, most of the
      current studies on climate change have only concerned with the mean values of the
      warming trend. Although many studies have been conducted concerning the responses
      of insects to climate change, studies that address the issue of diel asymmetric
      warming under field conditions are not found in the literature.
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a field climate manipulative
      experiment and investigated developmental and demographic responses to diel
      asymmetric warming in three grasshopper species (an early-season species
      Dasyhippus barbipes, a mid-season species Oedaleus asiaticus, and a late-season
      species Chorthippus fallax). It was found that warming generally advanced the
      development of eggs and nymphs, but had no apparent impacts on the hatching rate
      of eggs, the emergence rate of nymphs and the survival and fecundity of adults in
      all the three species. Nighttime warming was more effective in advancing egg
      development than the daytime warming. The emergence time of adults was
      differentially advanced by warming in the three species; it was advanced by 5.64
      days in C. fallax, 3.55 days in O. asiaticus, and 1.96 days in D. barbipes. This
      phenological advancement was associated with increases in the effective GDDs
      accumulation. CONCLUSIONS/SIGNIFICANCE: Results in this study indicate that the
      responses of the three grasshopper species to warming are influenced by several
      factors, including species traits, developmental stage, and the thermal
      sensitivity of the species. Moreover, species with diapausing eggs are less
      responsive to changes in temperature regimes, suggesting that development of
      diapausing eggs is a protective mechanism in early-season grasshopper for
      avoiding the risk of pre-winter hatching. Our results highlight the need to
      consider the complex relationships between climate change and specificity
      responses of invertebrates.

PMID- 22848594
TI  - Antagonism pattern detection between microRNA and target expression in Ewing's
      sarcoma.
AB  - MicroRNAs (miRNAs) have emerged as fundamental regulators that silence gene
      expression at the post-transcriptional and translational levels. The
      identification of their targets is a major challenge to elucidate the regulated
      biological processes. The overall effect of miRNA is reflected on target mRNA
      expression, suggesting the design of new investigative methods based on high
      throughput experimental data such as miRNA and transcriptome profiles. We propose
      a novel statistical measure of non-linear dependence between miRNA and mRNA
      expression, in order to infer miRNA-target interactions. This approach, which we
      name antagonism pattern detection, is based on the statistical recognition of a
      triangular-shaped pattern in miRNA-target expression profiles. This pattern is
      observed in miRNA-target expression measurements since their simultaneously
      elevated expression is statistically under-represented in the case of miRNA
      silencing effect. The proposed method enables miRNA target prediction to strongly
      rely on cellular context and physiological conditions reflected by expression
      data. The procedure has been assessed on synthetic datasets and tested on a set
      of real positive controls. Then it has been applied to analyze expression data
      from Ewing's sarcoma patients. The antagonism relationship is evaluated as a good
      indicator of real miRNA-target biological interaction. The predicted targets are
      consistently enriched for miRNA binding site motifs in their 3'UTR. Moreover, we
      reveal sets of predicted targets for each miRNA sharing important biological
      function. The procedure allows us to infer crucial miRNA regulators and their
      potential targets in Ewing's sarcoma disease. It can be considered as a valid
      statistical approach to discover new insights in the miRNA regulatory mechanisms.

PMID- 22848596
TI  - ExoU activates NF-kappaB and increases IL-8/KC secretion during Pseudomonas
      aeruginosa infection.
AB  - ExoU, a Pseudomonas aeruginosa cytotoxin injected into host cytosol by type III
      secretion system, exhibits a potent proinflammatory activity that leads to a
      marked recruitment of neutrophils to infected tissues. To evaluate the mechanisms
      that account for neutrophil infiltration, we investigated the effect of ExoU on
      IL-8 secretion and NF-kappaB activation. We demonstrate that ExoU increases IL-8
      mRNA and protein levels in P. aeruginosa-infected epithelial and endothelial cell
      lines. Also, ExoU induces the nuclear translocation of p65/p50 NF-kappaB
      transactivator heterodimer as well as NF-kappaB-dependent transcriptional
      activity. ChIP assays clearly revealed that ExoU promotes p65 binding to NF
      kappaB site in IL-8 promoter and the treatment of cultures with the NF-kappaB
      inhibitor Bay 11-7082 led to a significant reduction in IL-8 mRNA levels and
      protein secretion induced by ExoU. These results were corroborated in a murine
      model of pneumonia that revealed a significant reduction in KC secretion and
      neutrophil infiltration in bronchoalveolar lavage when mice were treated with Bay
      11-7082 before infection with an ExoU-producing strain. In conclusion, our data
      demonstrate that ExoU activates NF-kappaB, stimulating IL-8 expression and
      secretion during P. aeruginosa infection, and unveils a new mechanism triggered
      by this important virulence factor to interfere in host signaling pathways.

PMID- 22848595
TI  - Growth of mouse oocytes to maturity from premeiotic germ cells in vitro.
AB  - In the present study, we established an in vitro culture system suitable for
      generating fertilizable oocytes from premeiotic mouse female germ cells. These
      results were achieved after first establishing an in vitro culture system
      allowing immature oocytes from 12-14 day-old mice to reach meiotic maturation
      through culture onto preantral granulosa cell (PAGC) monolayers in the presence
      of Activin A (ActA). To generate mature oocytes from premeiotic germ cells,
      pieces of ovaries from 12.5 days post coitum (dpc) embryos were cultured in
      medium supplemented with ActA for 28 days and the oocytes formed within the
      explants were isolated and cocultured onto PAGC monolayers in the presence of
      ActA for 6-7 days. The oocytes were then subjected to a final meiotic maturation
      assay to evaluate their capability to undergo germinal vesicle break down (GVBD)
      and reach the metaphase II (MII) stage. We found that during the first 28 days of
      culture, a significant number of oocytes within the ovarian explants reached
      nearly full growth and formed preantral follicle-like structures with the
      surrounding somatic cells. GSH level and Cx37 expression in the oocytes within
      the explants were indicative of proper developmental conditions. Moreover, the
      imprinting of Igf2r and Peg3 genes in these oocytes was correctly established.
      Further culture onto PAGCs in the presence of ActA allowed about 16% of the
      oocytes to undergo GVBD, among which 17% reached the MII stage during the final
      16-18 hr maturation culture. These MII oocytes showed normal spindle and
      chromosome assembly and a correct ERK1/2 activity. About 35% of the in vitro
      matured oocytes were fertilized and 53.44% of them were able to reach the 2-cell
      stage. Finally, around 7% of the 2-cell embryos developed to the
      morula/blastocyst stage.

PMID- 22848597
TI  - beta,beta-Dimethylacrylshikonin induces mitochondria dependent apoptosis through
      ERK pathway in human gastric cancer SGC-7901 cells.
AB  - beta,beta-Dimethylacrylshikonin, one of the active components in the root
      extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study,
      we discussed the molecular mechanisms of beta,beta-dimethylacrylshikonin in the
      apoptosis of SGC-7901 cells. beta,beta-Dimethylacrylshikonin reduced the cell
      viability of SGC-7901 cells in a dose- and time-dependent manner and induced cell
      apoptosis. beta,beta-Dimethylacrylshikonin treatment in SGC-7901 cells down
      regulated the expression of XIAP, cIAP-2, and Bcl-2 and up-regulated the
      expression of Bak and Bax and caused the loss of mitochondrial membrane potential
      and release of cytochrome c. Additionally, beta,beta-dimethylacrylshikonin
      treatment led to activation of caspases-9, 8 and 3, and cleavage of poly (ADP
      ribose) polymerase (PARP), which was abolished by pretreatment with the pan
      caspase inhibitor Z-VAD-FMK. beta,beta-Dimethylacrylshikonin induced
      phosphorylation of extracellular signal-regulated kinase (ERK) in SGC-7901 cells.
      U0126, a specific MEK inhibitor, blocked the ERK activation by beta,beta
      dimethylacrylshikonin and abrogated beta,beta-dimethylacrylshikonin -induced
      apoptosis. Our results demonstrated that beta,beta-dimethylacrylshikonin
      inhibited growth of gastric cancer SGC-7901 cells by inducing ERK signaling
      pathway, and provided a clue for preclinical and clinical evaluation of beta,beta
      dimethylacrylshikonin for gastric cancer therapy.

PMID- 22848598
TI  - Tip60 HAT activity mediates APP induced lethality and apoptotic cell death in the
      CNS of a Drosophila Alzheimer's disease model.
AB  - Histone acetylation of chromatin promotes dynamic transcriptional responses in
      neurons that influence neuroplasticity critical for cognitive ability. It has
      been demonstrated that Tip60 histone acetyltransferase (HAT) activity is involved
      in the transcriptional regulation of genes enriched for neuronal function as well
      as the control of synaptic plasticity. Accordingly, Tip60 has been implicated in
      the neurodegenerative disorder Alzheimer's disease (AD) via transcriptional
      regulatory complex formation with the AD linked amyloid precursor protein (APP)
      intracellular domain (AICD). As such, inappropriate complex formation may
      contribute to AD-linked neurodegeneration by misregulation of target genes
      involved in neurogenesis; however, a direct and causative epigenetic based role
      for Tip60 HAT activity in this process during neuronal development in vivo
      remains unclear. Here, we demonstrate that nervous system specific loss of Tip60
      HAT activity enhances APP mediated lethality and neuronal apoptotic cell death in
      the central nervous system (CNS) of a transgenic AD fly model while remarkably,
      overexpression of Tip60 diminishes these defects. Notably, all of these effects
      are dependent upon the C-terminus of APP that is required for transcriptional
      regulatory complex formation with Tip60. Importantly, we show that the expression
      of certain AD linked Tip60 gene targets critical for regulating apoptotic
      pathways are modified in the presence of APP. Our results are the first to
      demonstrate a functional interaction between Tip60 and APP in mediating nervous
      system development and apoptotic neuronal cell death in the CNS of an AD fly
      model in vivo, and support a novel neuroprotective role for Tip60 HAT activity in
      AD neurodegenerative pathology.

PMID- 22848599
TI  - Amniocentesis, maternal psychopathology and prenatal representations of
      attachment: a prospective comparative study.
AB  - BACKGROUND: The aim of the study was to characterize the maternal dimensions of
      anxiety, depression and prenatal attachment in women undergoing an amniocentesis.
      METHODOLOGY/PRINCIPAL FINDINGS: A prospective observational study was conducted.
      Women were referred to early amniocentesis for increased nuchal translucency,
      elevated biochemical markers or advanced maternal age. All participants had 3
      prenatal (16-18, 20-24, 30-34 weeks of gestation) and one postnatal (30-45 days)
      interviews reviewing for demographic, medical, and psychiatric information (STAI
      State-Trait Anxiety Inventory; EPDS: Edinburgh Postnatal Depression Scale; IRMAG:
      Interview of Maternal Representations of Attachment during pregnancy). We
      investigated 232 pregnant women who undergone an amniocentesis compared with 160
      pregnant controls. Following the procedure, the amniocentesis group experienced
      transiently significantly higher levels of state-anxiety on the STAI (44.6 vs.
      39.3) and depression as measured by the EPDS (9.4 vs. 6.3) than the controls.
      Overall in both groups, the maternal representations of attachment were well
      integrated and balanced, but the amniocentesis group experienced significantly
      more mother-directed representations. CONCLUSIONS/SIGNIFICANCE: Amniocentesis is
      associated with higher affective adaptive reactions that tend to normalize during
      the pregnancy, with overall preserved maternal fetal representations of
      attachment.

PMID- 22848600
TI  - Lowered risk of nasopharyngeal carcinoma and intake of plant vitamin, fresh fish,
      green tea and coffee: a case-control study in Taiwan.
AB  - BACKGROUND: A case-control study was conducted to evaluate the role of adult diet
      on nasopharyngeal carcinoma (NPC) in Taiwan. METHODS: A total of 375 incident NPC
      cases and 327 controls matched to the cases on sex, age, and residence were
      recruited between July 1991 and December 1994. A structured questionnaire
      inquiring complete dietary history, socio-demographic characteristics, and other
      potential confounding factors was used in the personal interview. Unconditional
      logistic regression analysis was used to estimate multivariate-adjusted odds
      ratio (OR(adj)) with 95% confidence interval (CI) after accounting for known risk
      factors. RESULTS: Fresh fish (OR(adj), 0.56; 95% CI, 0.38-0.83 for the highest
      vs. lowest tertile of intake), green tea (OR(adj), 0.61; 95% CI, 0.40-0.91 for
      drinking >=1 times/week vs. never) and coffee (OR(adj), 0.56; 95% CI, 0.37-0.85
      for drinking >=0.5 times/week vs. never) were inversely associated with the NPC
      risk. No association with NPC risk was observed for the intake of meats, salted
      fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources
      was associated with a decreased NPC risk (OR(adj), 0.62; 95% CI, 0.41-0.94 for
      the highest vs. lowest tertile). CONCLUSION: The study findings suggest that
      certain adult dietary patterns might protect against the development of NPC.

PMID- 22848601
TI  - Foxi2 is an animally localized maternal mRNA in Xenopus, and an activator of the
      zygotic ectoderm activator Foxi1e.
AB  - Foxi1e is a zygotic transcription factor that is essential for the expression of
      early ectodermal genes. It is expressed in a highly specific pattern, only in the
      deep cell layers of the animal hemisphere, and in a mosaic pattern in which
      expressing cells are interspersed with non-expressing cells. Previous work has
      shown that several signals in the blastula control this expression pattern,
      including nodals, the TGFbeta family member Vg1, and Notch. However, these are
      all inhibitory, which raises the question of what activates Foxi1e. In this work,
      we show that a related Forkhead family protein, Foxi2, is a maternal activator of
      Foxi1e. Foxi2 mRNA is maternally encoded, and highly enriched in animal
      hemisphere cells of the blastula. ChIP assays show that it acts directly on
      upstream regulatory elements of Foxi1e. Its effect is specific, since animal
      cells depleted of Foxi2 are able to respond normally to mesoderm inducing signals
      from vegetal cells. Foxi2 thus acts as a link between the oocyte and the early
      pathway to ectoderm, in a similar fashion to the vegetally localized VegT acts to
      initiate endoderm and mesoderm formation.

PMID- 22848602
TI  - Encoding of physics concepts: concreteness and presentation modality reflected by
      human brain dynamics.
AB  - Previous research into working memory has focused on activations in different
      brain areas accompanying either different presentation modalities (verbal vs. non
      verbal) or concreteness (abstract vs. concrete) of non-science concepts. Less
      research has been conducted investigating how scientific concepts are learned and
      further processed in working memory. To bridge this gap, the present study
      investigated human brain dynamics associated with encoding of physics concepts,
      taking both presentation modality and concreteness into account. Results of this
      study revealed greater theta and low-beta synchronization in the anterior
      cingulate cortex (ACC) during encoding of concrete pictures as compared to the
      encoding of both high and low imageable words. In visual brain areas, greater
      theta activity accompanying stimulus onsets was observed for words as compared to
      pictures while stronger alpha suppression was observed in responses to pictures
      as compared to words. In general, the EEG oscillation patterns for encoding words
      of different levels of abstractness were comparable but differed significantly
      from encoding of pictures. These results provide insights into the effects of
      modality of presentation on human encoding of scientific concepts and thus might
      help in developing new ways to better teach scientific concepts in class.

PMID- 22848603
TI  - Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental
      atherosclerotic heart disease.
AB  - BACKGROUND: Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune
      modulating lipid mediators involved in inflammatory diseases, in particular
      asthma. Here, we investigated whether cys-LT signaling, in the context of
      atherosclerotic heart disease, compromises the myocardial microcirculation and
      its response to hypoxic stress. To this end, we examined Apoe(-/-) mice fed a
      hypercholesterolemic diet and analysed the expression of key enzymes of the cys
      LT pathway and their receptors (CysLT1/CysLT2) in normal and hypoxic myocardium
      as well as the potential contribution of cys-LT signaling to the acute myocardial
      response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from
      Apoe(-/-) mice demonstrated signs of chronic inflammation with fibrosis,
      increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J
      control mice. In addition, we found increased leukotriene C(4) synthase (LTC(4)S)
      and CysLT1 expression in the myocardium of Apoe(-/-) mice. Acute bouts of hypoxia
      further induced LTC(4)S expression, increased LTC(4)S enzyme activity and CysLT1
      expression, and were associated with increased extension of hypoxic areas within
      the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a
      selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress
      reduced myocardial hypoxic areas in Apoe(-/-) mice to levels equal to those
      observed under normoxic conditions. In human heart biopsies from 14 patients with
      chronic coronary artery disease mRNA expression levels of LTC(4)S and CysLT1 were
      increased in chronic ischemic compared to non-ischemic myocardium, constituting a
      molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest
      that CysLT1 antagonists may have protective effects on the hypoxic heart, and
      improve the oxygen supply to areas of myocardial ischemia, for instance during
      episodes of sleep apnea.

PMID- 22848604
TI  - A quorum sensing-disrupting brominated thiophenone with a promising therapeutic
      potential to treat luminescent vibriosis.
AB  - Vibrio harveyi is amongst the most important bacterial pathogens in aquaculture.
      Novel methods to control this pathogen are needed since many strains have
      acquired resistance to antibiotics. We previously showed that quorum sensing
      disrupting furanones are able to protect brine shrimp larvae against vibriosis.
      However, a major problem of these compounds is that they are toxic toward higher
      organisms and therefore, they are not safe to be used in aquaculture. The
      synthesis of brominated thiophenones, sulphur analogues of the quorum sensing
      disrupting furanones, has recently been reported. In the present study, we report
      that these compounds block quorum sensing in V. harveyi at concentrations in the
      low micromolar range. Bioluminescence experiments with V. harveyi quorum sensing
      mutants and a fluorescence anisotropy assay indicated that the compounds disrupt
      quorum sensing in this bacterium by decreasing the ability of the quorum sensing
      master regulator LuxR to bind to its target promoter DNA. In vivo challenge tests
      with gnotobiotic brine shrimp larvae showed that thiophenone compound TF310, (Z)
      4-((5-(bromomethylene)-2-oxo-2,5-dihydrothiophen-3-yl)methoxy)-4-oxobutanoic
      acid, completely protected the larvae from V. harveyi BB120 when dosed to the
      culture water at 2.5 uM or more, whereas severe toxicity was only observed at 250
      uM. This makes TF310 showing the highest therapeutic index of all quorum sensing
      disrupting compounds tested thus far in our brine shrimp model system.

PMID- 22848605
TI  - Self-love or other-love? Explicit other-preference but implicit self-preference.
AB  - Do humans prefer the self even over their favorite other person? This question
      has pervaded philosophy and social-behavioral sciences. Psychology's distinction
      between explicit and implicit preferences calls for a two-tiered solution. Our
      evolutionarily-based Dissociative Self-Preference Model offers two hypotheses.
      Other-preferences prevail at an explicit level, because they convey caring for
      others, which strengthens interpersonal bonds--a major evolutionary advantage.
      Self-preferences, however, prevail at an implicit level, because they facilitate
      self-serving automatic behavior, which favors the self in life-or-die situations
      also a major evolutionary advantage. We examined the data of 1,519 participants,
      who completed an explicit measure and one of five implicit measures of
      preferences for self versus favorite other. The results were consistent with the
      Dissociative Self-Preference Model. Explicitly, participants preferred their
      favorite other over the self. Implicitly, however, they preferred the self over
      their favorite other (be it their child, romantic partner, or best friend).
      Results are discussed in relation to evolutionary theorizing on self-deception.

PMID- 22848606
TI  - Different transcriptional response to Xanthomonas citri subsp. citri between
      kumquat and sweet orange with contrasting canker tolerance.
AB  - Citrus canker disease caused by Xanthomonas citri subsp. citri (Xcc) is one of
      the most devastating biotic stresses affecting the citrus industry. Meiwa kumquat
      (Fortunella crassifolia) is canker-resistant, while Newhall navel orange (Citrus
      sinensis Osbeck) is canker-sensitive. To understand the molecular mechanisms
      underlying the differences in responses to Xcc, transcriptomic profiles of these
      two genotypes following Xcc attack were compared by using the Affymetrix citrus
      genome GeneChip. A total of 794 and 1324 differentially expressed genes (DEGs)
      were identified as canker-responsive genes in Meiwa and Newhall, respectively. Of
      these, 230 genes were expressed in common between both genotypes, while 564 and
      1094 genes were only significantly expressed in either Meiwa or Newhall. Gene
      ontology (GO) annotation and Singular Enrichment Analysis (SEA) of the DEGs
      showed that genes related to the cell wall and polysaccharide metabolism were
      induced for basic defense in both Meiwa and Newhall, such as chitinase, glucanase
      and thaumatin-like protein. Moreover, apart from inducing basic defense, Meiwa
      showed specially upregulated expression of several genes involved in the response
      to biotic stimulus, defense response, and cation binding as comparing with
      Newhall. And in Newhall, abundant photosynthesis-related genes were significantly
      down-regulated, which may be in order to ensure the basic defense. This study
      revealed different molecular responses to canker disease in Meiwa and Newhall,
      affording insight into the response to canker and providing valuable information
      for the identification of potential genes for engineering canker tolerance in the
      future.

PMID- 22848607
TI  - Diagnostic features of emotional expressions are processed preferentially.
AB  - Diagnostic features of emotional expressions are differentially distributed
      across the face. The current study examined whether these diagnostic features are
      preferentially attended to even when they are irrelevant for the task at hand or
      when faces appear at different locations in the visual field. To this aim,
      fearful, happy and neutral faces were presented to healthy individuals in two
      experiments while measuring eye movements. In Experiment 1, participants had to
      accomplish an emotion classification, a gender discrimination or a passive
      viewing task. To differentiate fast, potentially reflexive, eye movements from a
      more elaborate scanning of faces, stimuli were either presented for 150 or 2000
      ms. In Experiment 2, similar faces were presented at different spatial positions
      to rule out the possibility that eye movements only reflect a general bias for
      certain visual field locations. In both experiments, participants fixated the eye
      region much longer than any other region in the face. Furthermore, the eye region
      was attended to more pronouncedly when fearful or neutral faces were shown
      whereas more attention was directed toward the mouth of happy facial expressions.
      Since these results were similar across the other experimental manipulations,
      they indicate that diagnostic features of emotional expressions are
      preferentially processed irrespective of task demands and spatial locations.
      Saliency analyses revealed that a computational model of bottom-up visual
      attention could not explain these results. Furthermore, as these gaze preferences
      were evident very early after stimulus onset and occurred even when saccades did
      not allow for extracting further information from these stimuli, they may reflect
      a preattentive mechanism that automatically detects relevant facial features in
      the visual field and facilitates the orientation of attention towards them. This
      mechanism might crucially depend on amygdala functioning and it is potentially
      impaired in a number of clinical conditions such as autism or social anxiety
      disorders.

PMID- 22848608
TI  - Subthalamic nucleus electrical stimulation modulates calcium activity of nigral
      astrocytes.
AB  - BACKGROUND: The substantia nigra pars reticulata (SNr) is a major output nucleus
      of the basal ganglia, delivering inhibitory efferents to the relay nuclei of the
      thalamus. Pathological hyperactivity of SNr neurons is known to be responsible
      for some motor disorders e.g. in Parkinson's disease. One way to restore this
      pathological activity is to electrically stimulate one of the SNr input, the
      excitatory subthalamic nucleus (STN), which has emerged as an effective treatment
      for parkinsonian patients. The neuronal network and signal processing of the
      basal ganglia are well known but, paradoxically, the role of astrocytes in the
      regulation of SNr activity has never been studied. PRINCIPAL FINDINGS: In this
      work, we developed a rat brain slice model to study the influence of spontaneous
      and induced excitability of afferent nuclei on SNr astrocytes calcium activity.
      Astrocytes represent the main cellular population in the SNr and display
      spontaneous calcium activities in basal conditions. Half of this activity is
      autonomous (i.e. independent of synaptic activity) while the other half is
      dependent on spontaneous glutamate and GABA release, probably controlled by the
      pace-maker activity of the pallido-nigral and subthalamo-nigral loops.
      Modification of the activity of the loops by STN electrical stimulation disrupted
      this astrocytic calcium excitability through an increase of glutamate and GABA
      releases. Astrocytic AMPA, mGlu and GABA(A) receptors were involved in this
      effect. SIGNIFICANCE: Astrocytes are now viewed as active components of neural
      networks but their role depends on the brain structure concerned. In the SNr,
      evoked activity prevails and autonomous calcium activity is lower than in the
      cortex or hippocampus. Our data therefore reflect a specific role of SNr
      astrocytes in sensing the STN-GPe-SNr loops activity and suggest that SNr
      astrocytes could potentially feedback on SNr neuronal activity. These findings
      have major implications given the position of SNr in the basal ganglia network.

PMID- 22848609
TI  - Elevated IKKalpha accelerates the differentiation of human neuronal progenitor
      cells and induces MeCP2-dependent BDNF expression.
AB  - The IkappaB kinase alpha (IKKalpha) is implicated in the differentiation of
      epithelial and immune cells. We examined whether IKKalpha also plays a role in
      the differentiation and maturation of embryonic human neuronal progenitor cells
      (NPCs). We find that expression of an extra copy of IKKalpha (IKKalpha+) blocks
      self-renewal and accelerates the differentiation of NPCs. This coincides with
      reduced expression of the Repressor Element Silencing Transcription Factor/Neuron
      Restrictive Silencing Factor (REST/NRSF), which is a prominent inhibitor of
      neurogenesis, and subsequent induction of the pro-differentiation non-coding RNA,
      miR-124a. However, the effects of IKKalpha on REST/NRSF and miR-124a expression
      are likely to be indirect. IKKalpha+ neurons display extensive neurite outgrowth
      and accumulate protein markers of neuronal maturation such as SCG10/stathmin-2,
      postsynaptic density 95 (PSD95), syntaxin, and methyl-CpG binding protein 2
      (MeCP2). Interestingly, IKKalpha associates with MeCP2 in the nuclei of human
      neurons and can phosphorylate MeCP2 in vitro. Using chromatin immunoprecipitation
      assays, we find that IKKalpha is recruited to the exon-IV brain-derived
      neurotrophic factor (BDNF) promoter, which is a well-characterized target of
      MeCP2 activity. Moreover, IKKalpha induces the transcription of BDNF and
      knockdown expression of MeCP2 interferes with this event. These studies highlight
      a role for IKKalpha in accelerating the differentiation of human NPCs and
      identify IKKalpha as a potential regulator of MeCP2 function and BDNF expression.

PMID- 22848610
TI  - Returning to paid employment after stroke: the Psychosocial Outcomes In StrokE
      (POISE) cohort study.
AB  - OBJECTIVES: To determine which early modifiable factors are associated with
      younger stroke survivors' ability to return to paid work in a cohort study with
      12-months of follow-up conducted in 20 stroke units in the Stroke Services NSW
      clinical network. PARTICIPANTS: Were aged >17 and <65 years, recent (within 28
      days) stroke, able to speak English sufficiently to respond to study questions,
      and able to provide written informed consent. Participants with language or
      cognitive impairment were eligible to participate if their proxy provided consent
      and completed assessments on the participants' behalf. The main outcome measure
      was return to paid work during the 12 months following stroke. RESULTS: Of 441
      consented participants (average age 52 years, 68% male, 83% with ischemic
      stroke), 218 were in paid full-time and 53 in paid part-time work immediately
      before their stroke, of whom 202 (75%) returned to paid part- or full-time work
      within 12 months. Being male, female without a prior activity restricting
      illness, younger, independent in activities of daily living (ADL) at 28 days
      after stroke, and having private health insurance was associated with return to
      paid work, following adjustment for other illnesses and a history of depression
      before stroke (C statistic 0.81). Work stress and post stroke depression showed
      no such independent association. CONCLUSIONS: Given that independence in ADL is
      the strongest predictor of return to paid work within 12 months of stroke, these
      data reinforce the importance of reducing stroke-related disability and
      increasing independence for younger stroke survivors. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry ANZCTRN 12608000459325.

PMID- 22848611
TI  - A novel murine model of inflammatory bowel disease and inflammation-associated
      colon cancer with ulcerative colitis-like features.
AB  - Mutations that increase susceptibility to inflammatory bowel disease (IBD) have
      been identified in a number of genes in both humans and mice, but the factors
      that govern how these mutations contribute to IBD pathogenesis and result in
      phenotypic presentation as ulcerative colitis (UC) or Crohn disease (CD) are not
      well understood. In this study, mice deficient in both TNF and IL-10 (T/I mice)
      were found to spontaneously develop severe colitis soon after weaning, without
      the need for exogenous triggers. Colitis in T/I mice had clinical and histologic
      features similar to human UC, including a markedly increased risk of developing
      inflammation-associated colon cancer. Importantly, development of spontaneous
      colitis in these mice was prevented by antibiotic treatment. Consistent with the
      known role of Th17-driven inflammation in response to bacteria, T/I mice had
      elevated serumTh17-type cytokines when they developed spontaneous colitis and
      after systemic bacterial challenge via NSAID-induced degradation of the mucosal
      barrier. Although TNF production has been widely considered to be be pathogenic
      in IBD, these data indicate that the ability to produce normal levels of TNF
      actually protects against the spontaneous development of colitis in response to
      intestinal colonization by bacteria. The T/I mouse model will be useful for
      developing new rationally-based therapies to prevent and/or treat IBD and
      inflammation-associated colon cancer and may further provide important insights
      into the pathogenesis of UC in humans.

PMID- 22848612
TI  - In vitro expanded stem cells from the developing retina fail to generate
      photoreceptors but differentiate into myelinating oligodendrocytes.
AB  - Cell transplantation to treat retinal degenerative diseases represents an option
      for the replacement of lost photoreceptor cells. In vitro expandable cells
      isolated from the developing mammalian retina have been suggested as a potential
      source for the generation of high numbers of donor photoreceptors. In this study
      we used standardized culture conditions based on the presence of the mitogens FGF
      2 and EGF to generate high numbers of cells in vitro from the developing mouse
      retina. These presumptive 'retinal stem cells' ('RSCs') can be propagated as
      monolayer cultures over multiple passages, express markers of undifferentiated
      neural cells, and generate neuronal and glial cell types upon withdrawal of
      mitogens in vitro or following transplantation into the adult mouse retina. The
      proportion of neuronal differentiation can be significantly increased by stepwise
      removal of mitogens and inhibition of the notch signaling pathway. However,
      'RSCs', by contrast to their primary counterparts in vivo, i.e. retinal
      progenitor cells, loose the expression of retina-specific progenitor markers like
      Rax and Chx10 after passaging and fail to differentiate into photoreceptors both
      in vitro or after intraretinal transplantation. Notably, 'RSCs' can be induced to
      differentiate into myelinating oligodendrocytes, a cell type not generated by
      primary retinal progenitor cells. Based on these findings we conclude that 'RSCs'
      expanded in high concentrations of FGF-2 and EGF loose their retinal identity and
      acquire features of in vitro expandable neural stem-like cells making them an
      inappropriate cell source for strategies aimed at replacing photoreceptor cells
      in the degenerated retina.

PMID- 22848613
TI  - Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet
      syndrome.
AB  - BACKGROUND: Dravet syndrome is a severe form of epilepsy. Majority of patients
      have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A
      recent study has demonstrated that 16% of SCN1A-negative patients have a mutation
      in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account
      for only a very small proportion of families. TSPYL4 is a novel candidate gene
      within the locus 6q16.3-q22.31 identified by linkage study. OBJECTIVE: The
      present study examined the mutations in epileptic Chinese children with emphasis
      on Dravet syndrome. METHODS: A hundred children with severe epilepsy were divided
      into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A
      mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and
      patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and
      TSPYL4 mutations. RESULTS: Eighteen patients (9 males, 9 females) were diagnosed
      to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including
      truncating (7), splice site (2) and missense mutations (6). The truncating/splice
      site mutations were associated with moderate to severe degree of intellectual
      disability (p<0.05). During the progression of disease, 73% (11/15) had features
      fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15)
      had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was
      identified in one SCN1A-negative female patient with Dravet syndrome and a known
      PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also
      inherited a TSPYL4 p.G60R variant. CONCLUSION: A high percentage of SCN1A
      mutations was identified in our Chinese cohort of Dravet syndrome patients but
      none in the rest of patients. We demonstrated that truncating/splice site
      mutations were linked to moderate to severe intellectual disability in these
      patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4
      missense variant were identified in a patient with Dravet syndrome.

PMID- 22848614
TI  - Y-chromosome analysis in individuals bearing the Basarab name of the first
      dynasty of Wallachian kings.
AB  - Vlad III The Impaler, also known as Dracula, descended from the dynasty of
      Basarab, the first rulers of independent Wallachia, in present Romania. Whether
      this dynasty is of Cuman (an admixed Turkic people that reached Wallachia from
      the East in the 11(th) century) or of local Romanian (Vlach) origin is debated
      among historians. Earlier studies have demonstrated the value of investigating
      the Y chromosome of men bearing a historical name, in order to identify their
      genetic origin. We sampled 29 Romanian men carrying the surname Basarab, in
      addition to four Romanian populations (from counties Dolj, N = 38; Mehedinti, N =
      11; Cluj, N = 50; and Brasov, N = 50), and compared the data with the surrounding
      populations. We typed 131 SNPs and 19 STRs in the non-recombinant part of the Y
      chromosome in all the individuals. We computed a PCA to situate the Basarab
      individuals in the context of Romania and its neighboring populations. Different
      Y-chromosome haplogroups were found within the individuals bearing the Basarab
      name. All haplogroups are common in Romania and other Central and Eastern
      European populations. In a PCA, the Basarab group clusters within other Romanian
      populations. We found several clusters of Basarab individuals having a common
      ancestor within the period of the last 600 years. The diversity of haplogroups
      found shows that not all individuals carrying the surname Basarab can be direct
      biological descendants of the Basarab dynasty. The absence of Eastern Asian
      lineages in the Basarab men can be interpreted as a lack of evidence for a Cuman
      origin of the Basarab dynasty, although it cannot be positively ruled out. It can
      be therefore concluded that the Basarab dynasty was successful in spreading its
      name beyond the spread of its genes.

PMID- 22848615
TI  - Investigating the scope of resident patient care handoffs within neurosurgery.
AB  - INTRODUCTION: Handoffs are defined as verbal and written communications during
      patient care transitions. With the passage of recent ACMGE work hour rules
      further limiting the hours interns can spend in the hospital, many fear that more
      handoffs will occur, putting patient safety at risk. The issue of handoffs has
      not been studied in the neurosurgical literature. METHODS: A validated, 20
      question online-survey was sent to neurosurgical residents in all 98 accredited
      U.S. neurosurgery programs. Survey results were analyzed using tabulations.
      RESULTS: 449 surveys were completed yielding a 56% response rate. 63% of
      neurosurgical residents surveyed had not received formal instruction in what
      constitutes an effective handoff; 24% believe there is high to moderate
      variability among their co-residents in terms of the quality of the handoff
      provided; 55% experience three or more interruptions during handoffs on average.
      90% of neurosurgical residents surveyed say that handoff most often occurs in a
      quiet, private area and 56% report a high level of comfort for knowing the
      potential acute, critical issues affecting a patient when receiving a handoff.
      CONCLUSIONS: There needs to be more focused education devoted to learning
      effective patient-care handoffs in neurosurgical training programs. Increasingly,
      handing off a patient adequately and safely is becoming a required skill of
      residency.

PMID- 22848616
TI  - Nanoscale strain-hardening of keratin fibres.
AB  - Mammalian appendages such as hair, quill and wool have a unique structure
      composed of a cuticle, a cortex and a medulla. The cortex, responsible for the
      mechanical properties of the fibers, is an assemblage of spindle-shaped
      keratinized cells bound together by a lipid/protein sandwich called the cell
      membrane complex. Each cell is itself an assembly of macrofibrils around 300 nm
      in diameter that are paracrystalline arrays of keratin intermediate filaments
      embedded in a sulfur-rich protein matrix. Each macrofibril is also attached to
      its neighbors by a cell membrane complex. In this study, we combined atomic force
      microscopy based nano-indentation with peak-force imaging to study the
      nanomechanical properties of macrofibrils perpendicular to their axis. For
      indentation depths in the 200 to 500 nm range we observed a decrease of the
      dynamic elastic modulus at 1 Hz with increasing depth. This yielded an estimate
      of 1.6GPa for the lateral modulus at 1 Hz of porcupine quill's macrofibrils.
      Using the same data we also estimated the dynamic elastic modulus at 1 Hz of the
      cell membrane complex surrounding each macrofibril, i.e., 13GPa. A similar
      estimate was obtained independently through elastic maps of the macrofibrils
      surface obtained in peak-force mode at 1 kHz. Furthermore, the macrofibrillar
      texture of the cortical cells was clearly identified on the elasticity maps, with
      the boundaries between macrofibrils being 40-50% stiffer than the macrofibrils
      themselves. Elasticity maps after indentation also revealed a local increase in
      dynamic elastic modulus over time indicative of a relaxation induced strain
      hardening that could be explained in term of a alpha-helix to beta-sheet
      transition within the macrofibrils.

PMID- 22848617
TI  - Requirement for a uroplakin 3a-like protein in the development of zebrafish
      pronephric tubule epithelial cell function, morphogenesis, and polarity.
AB  - Uroplakin (UP)3a is critical for urinary tract development and function; however,
      its role in these processes is unknown. We examined the function of the UP3a-like
      protein Upk3l, which was expressed at the apical surfaces of the epithelial cells
      that line the pronephric tubules (PTs) of the zebrafish pronephros. Embryos
      treated with upk3l-targeted morpholinos showed decreased pronephros function,
      which was attributed to defects in PT epithelial cell morphogenesis and
      polarization including: loss of an apical brush border and associated phospho-ERM
      proteins, apical redistribution of the basolateral Na(+)/K(+)-ATPase, and altered
      or diminished expression of the apical polarity complex proteins Prkcz (atypical
      protein kinase C zeta) and Pard3 (Par3). Upk3l missing its C-terminal cytoplasmic
      domain or containing mutations in conserved tyrosine or proline residues did not
      rescue, or only partially rescued the effects of Upk3l depletion. Our studies
      indicate that Upk3l promotes epithelial polarization and morphogenesis, likely by
      forming or stimulating interactions with cytoplasmic signaling or polarity
      proteins, and that defects in this process may underlie the pathology observed in
      UP3a knockout mice or patients with renal abnormalities that result from altered
      UP3a expression.

PMID- 22848618
TI  - PGC-1alpha is dispensable for exercise-induced mitochondrial biogenesis in
      skeletal muscle.
AB  - Exercise confers numerous health benefits, many of which are thought to stem from
      exercise-induced mitochondrial biogenesis (EIMB) in skeletal muscle. The
      transcriptional coactivator PGC-1alpha, a potent regulator of metabolism in
      numerous tissues, is widely believed to be required for EIMB. We show here that
      this is not the case. Mice engineered to lack PGC-1alpha specifically in skeletal
      muscle (Myo-PGC-1alphaKO mice) retained intact EIMB. The exercise capacity of
      these mice was comparable to littermate controls. Induction of metabolic genes
      after 2 weeks of in-cage voluntary wheel running was intact. Electron microscopy
      revealed no gross abnormalities in mitochondria, and the mitochondrial biogenic
      response to endurance exercise was as robust in Myo-PGC-1alphaKO mice as in
      wildtype mice. The induction of enzymatic activity of the electron transport
      chain by exercise was likewise unperturbed in Myo-PGC-1alphaKO mice. These data
      demonstrate that PGC-1alpha is dispensable for exercise-induced mitochondrial
      biogenesis in skeletal muscle, in sharp contrast to the prevalent assumption in
      the field.

PMID- 22848619
TI  - Salvage liver transplantation for patients with recurrent hepatocellular
      carcinoma after curative resection.
AB  - OBJECTIVE: To summarize the experience with salvage liver transplantation (SLT)
      for patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic
      resection in a single center. METHODS: A total of 376 adult patients with HCC
      underwent orthotopic liver transplantation (OLT) at Organ Transplantation Center,
      the First Affiliated Hospital of Sun Yat-sen University, between 2004 and 2008.
      Among these patients, 36 underwent SLT after primary liver curative resection due
      to intrahepatic recurrence. During the same period, one hundred and forty-seven
      patients with HCC within Milan criteria underwent primary OLT (PLTW group), the
      intra-operative and post-operative parameters were compared between these two
      groups. Furthermore, we compared tumor recurrence and patient survival of
      patients with SLT to 156 patients with HCC beyond Milan criteria (PLTB group).
      Cox Hazard regression was made to identify the risk factors for tumor recurrence.
      RESULTS: The median interval between initial liver resection and SLT was 35
      months (1-63 months). The intraoperative blood loss (P<0.05) and transfusion
      volume (P<0.05) were larger in the SLT group than in the PLTW group. The
      operation time was longer in the SLT group (P<0.05). The post-operative
      complications incidence, tumor recurrence rate, patients' survival rate, and
      tumor-free survival rate were comparable between these two groups (all P>0.05).
      When compared to those patients with HCC beyond Milan criteria undergoing primary
      OLT, patients undergoing SLT achieved a better survival and a lower tumor
      recurrence. Cox Proportional Hazards model showed that vascular invasion,
      including macrovascular and microvascular invasion, as well as AFP level >400
      IU/L were risk factors for tumor recurrence after LT. CONCLUSIONS: In comparison
      with primary OLT, although SLT is associated with increased operation
      difficulties, it provides a good option for patients with HCC recurrence after
      curative resection.

PMID- 22848620
TI  - Prenatal stress and peripubertal stimulation of the endocannabinoid system
      differentially regulate emotional responses and brain metabolism in mice.
AB  - The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal
      axis mediate individual responses to emotionally salient stimuli. Their altered
      developmental adjustment may relate to the emergence of emotional disturbances.
      Although environmental influences regulate the individual phenotype throughout
      the entire lifespan, their effects may result particularly persistent during
      plastic developmental stages (e.g. prenatal life and adolescence). Here, we
      investigated whether prenatal stress--in the form of gestational exposure to
      corticosterone supplemented in the maternal drinking water (100 mg/l) during the
      last week of pregnancy--combined with a pharmacological stimulation of the ECS
      during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration-
      0.4 mg/kg--between postnatal days 29-38), influenced adult mouse emotional
      behaviour and brain metabolism measured through in vivo quantitative magnetic
      resonance spectroscopy. Compared to control mice, URB597-treated subjects showed,
      in the short-term, reduced locomotion and, in the long term, reduced motivation
      to execute operant responses to obtain palatable rewards paralleled by reduced
      levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to
      prenatal corticosterone showed increased behavioural anxiety and reduced
      locomotion in the elevated zero maze, and altered brain metabolism (increased
      glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl
      Aspartate in the hypothalamus). Present data further corroborate the view that
      prenatal stress and pharmacological ECS stimulation during adolescence
      persistently regulate emotional responses in adulthood. Yet, whilst we
      hypothesized these factors to be interactive in nature, we observed that the
      consequences of prenatal corticosterone administration were independent from
      those of ECS drug-induced stimulation during adolescence.

PMID- 22848621
TI  - Glutamatergic and GABAergic metabolism in mouse brain under chronic nicotine
      exposure: implications for addiction.
AB  - BACKGROUND AND PURPOSE: The effects of nicotine on cerebral metabolism and its
      influence on smoking behavior is poorly understood. An understanding of the
      chronic effects of nicotine on excitatory and inhibitory metabolic demand, and
      corresponding neurotransmission may provide clues for designing strategies for
      the optimal smoking cessation intervention. The objective of the current study
      was to investigate neuronal and astroglial metabolism in mice exposed to nicotine
      (0.5 and 2.0 mg/kg, s.c.) three times in a day for 4 weeks. EXPERIMENTAL
      APPROACH/PRINCIPAL FINDINGS: Metabolic measurements were carried out by co
      infusing [U-(13)C(6)]glucose and [2-(13)C]acetate, and monitoring (13)C labeling
      of amino acids in brain tissue extract using (1)H-[(13)C] and (13)C-[(1)H]-NMR
      spectroscopy. Concentration of (13)C-labeled glutamate-C4 was increased
      significantly from glucose and acetate with chronic nicotine treatment indicating
      an increase in glucose oxidation by glutamatergic neurons in all brain regions
      and glutamate-glutamine neurotransmitter cycle in cortical and subcortical
      regions. However, chronic nicotine treatment led to increased labeling of GABA-C2
      from glucose only in the cortical region. Further, increased labeling of
      glutamine-C4 from [2-(13)C]acetate is suggestive of increased astroglial activity
      in subcortical and cerebellum regions of brain with chronic nicotine treatment.
      CONCLUSIONS AND SIGNIFICANCE: Chronic nicotine exposure enhanced excitatory
      activity in the majority of brain regions while inhibitory and astroglial
      functions were enhanced only in selected brain regions.

PMID- 22848622
TI  - Analysis of autophagy genes in microalgae: Chlorella as a potential model to
      study mechanism of autophagy.
AB  - BACKGROUND: Microalgae, with the ability to mitigate CO(2) emission and produce
      carbohydrates and lipids, are considered one of the most promising resources for
      producing bioenergy. Recently, we discovered that autophagy plays a critical role
      in the metabolism of photosynthetic system and lipids production. So far, more
      than 30-autophagy related (ATG) genes in all subtypes of autophagy have been
      identified. However, compared with yeast and mammals, in silico and experimental
      research of autophagy pathways in microalgae remained limited and fragmentary.
      PRINCIPAL FINDINGS: In this article, we performed a genome-wide analysis of ATG
      genes in 7 microalgae species and explored their distributions, domain structures
      and evolution. Eighteen "core autophagy machinery" proteins, four mammalian
      specific ATG proteins and more than 30 additional proteins (including "receptor
      adaptor" complexes) in all subtypes of autophagy were analyzed. Data revealed
      that receptor proteins in cytoplasm-to-vacuole targeting and mitophagy seem to be
      absent in microalgae. However, most of the "core autophagy machinery" and
      mammalian-specific proteins are conserved among microalgae, except for the ATG9
      cycling system in Chlamydomonas reinhardtii and the second ubiquitin-like protein
      conjugation complex in several algal species. The catalytic and binding residues
      in ATG3, ATG5, ATG7, ATG8, ATG10 and ATG12 are also conserved and the
      phylogenetic tree of ATG8 coincides well with the phylogenies. Chlorella contains
      the entire set of the core autophagy machinery. In addition, RT-PCR analysis
      verified that all crucial ATG genes tested are expressed during autophagy in both
      Chlorella and Chlamydomonas reinhardtii. Finally, we discovered that addition of
      3-Methyladenine (a PI3K specific inhibitor) could suppress the formation of
      autophagic vacuoles in Chlorella. CONCLUSIONS: Taken together, Chlorella may
      represent a potential model organism to investigate autophagy pathways in
      photosynthetic eukaryotes. The study will not only promote understanding of the
      general features of autophagic pathways, but also benefit the production of
      Chlorella-derived biofuel with future commercial applications.

PMID- 22848623
TI  - Failure of long-term memory formation in juvenile snails is determined by
      acetylation status of histone H3 and can be improved by NaB treatment.
AB  - BACKGROUND: Animals' capacities for different forms of learning do not mature
      simultaneously during ontogenesis but the molecular mechanisms behind the delayed
      development of specific types of memory are not fully understood. Mollusks are
      considered to be among the best models to study memory formation at the molecular
      level. Chromatin remodeling in developmental processes, as well as in long-term
      memory formation, was recently shown to play a major role. Histone acetylation is
      a key process in the chromatin remodeling and is regulated through the signaling
      cascades, for example MAPK/ERK. Previously, we found that MAPK/ERK is a key
      pathway in the formation of the food aversion reflex in Helix. Pretreatment with
      upstream ERK kinase inhibitor PD98059 prevented food avoidance learning in adult
      Helix. In contrast to adult snails, juveniles possess immature plasticity
      mechanisms of the avoidance reflex until the age of 2-3 months while the MAPK/ERK
      cascade is not activated after aversive learning. In the present study, we
      focused on the potential MAPK/ERK target--histone H3. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we found that a significant increase in histone H3 acetylation
      occurs in adult animals after learning, whereas no corresponding increase was
      observed in juveniles. The acetylation of histone H3 is regulated by ERK kinase,
      since the upstream ERK kinase inhibitor PD98059 prevented the increase of histone
      H3 acetylation upon learning. We found that the injection of histone deacetylase
      inhibitor sodium butyrate (NaB) prior to training led to induction in histone H3
      acetylation and significantly ameliorated long-term memory formation in juvenile
      snails. CONCLUSIONS/SIGNIFICANCE: Thus, MAPK/ERK-dependent histone H3 acetylation
      plays an essential role in the formation of food aversion in Helix. Dysfunction
      of the MAPK/ERK dependent histone H3 acetylation might determine the deficiency
      of avoidance behavior and long-term plasticity in juvenile animals. Stimulation
      of histone H3 acetylation in juvenile animals by NaB promoted avoidance
      plasticity.

PMID- 22848624
TI  - Pollutant dehalogenation capability may depend on the trophic evolutionary
      history of the organism: PBDEs in freshwater food webs.
AB  - Organohalogen compounds are some of the most notorious persistent pollutants
      disturbing the Earth biosphere. Although human-made, these chemicals are not
      completely alien to living systems. A large number of natural organohalogens,
      part of the secondary metabolism, are involved in chemical trophic interactions.
      Surprisingly, the relationship between organisms' trophic position and synthetic
      organohalogen biotransformation capability has not been investigated. We studied
      the case for polybromodiphenyl ethers (PBDE), a group of flame-retardants of
      widespread use in the recent years, in aquatic food webs from remote mountain
      lakes. These relatively simple ecosystems only receive pollution by atmospheric
      transport. A large predominance of the PBDE congener currently in use in Europe,
      BDE-209, largely dominated the PBDE composition of the basal resources of the
      food web. In contrast, primary consumers (herbivores and detritivores) showed a
      low proportion of BDE-209, and dominance of several less brominated congeners
      (e.g. BDE-100, BDE47). Secondary consumers (predators) showed large
      biomagnification of BDE-209 compare to other congeners. Finally, top predator
      fish characterized by low total PBDE concentrations. Examination of the bromine
      stable isotopic composition indicates that primary consumers showed higher PBDE
      biotransformation capability than secondary consumers. We suggest that the
      evolutionary response of primary consumers to feeding deterrents would have pre
      adapted them for PBDE biotransformation. The observed few exceptions, some insect
      taxa, can be interpreted in the light of the trophic history of the evolutionary
      lineage of the organisms. Bromine isotopic composition in fish indicates that low
      PBDE values are due to not only biotransformation but also to some other process
      likely related to transport. Our finding illustrates that organohalogen compounds
      may strongly disturb ecosystems even at low concentrations, since the species
      lacking or having scarce biotransformation capability may be selectively more
      exposed to these halogenated hydrophobic semi-volatile organic pollutants due to
      their high bioaccumulation potential.

PMID- 22848625
TI  - Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR
      inhibition.
AB  - mTOR inhibitors are used clinically to treat renal cancer but are not curative.
      Here we show that autophagy is a resistance mechanism of human renal cell
      carcinoma (RCC) cell lines to mTOR inhibitors. RCC cell lines have high basal
      autophagy that is required for survival to mTOR inhibition. In RCC4 cells,
      inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases
      (RIPKs) and this is blocked by autophagy inhibition, which induces RIPK- and ROS
      dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of
      mitochondria is required for cell survival since mTOR inhibition turns off Nrf2
      antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an
      imbalance between ROS production and defense, causing necroptosis that may
      enhance cancer treatment efficacy.

PMID- 22848626
TI  - Silibinin inhibits HIV-1 infection by reducing cellular activation and
      proliferation.
AB  - Purified silymarin-derived natural products from the milk thistle plant (Silybum
      marianum) block hepatitis C virus (HCV) infection and inhibit T cell
      proliferation in vitro. An intravenous formulation of silibinin (SIL), a major
      component of silymarin, displays anti-HCV effects in humans and also inhibits T
      cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in
      TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided
      with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+
      cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4
      and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by
      cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the
      activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest
      that SIL attenuated cellular functions involved in T-cell activation,
      proliferation, and HIV-1 infection. Silymarin-derived compounds provide
      cytoprotection by suppressing virus infection, immune activation, and
      inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV
      co-infected subjects.

PMID- 22848627
TI  - Involvement of host stroma cells and tissue fibrosis in pancreatic tumor
      development in transgenic mice.
AB  - INTRODUCTION: Stroma cells and extracellular matrix (ECM) components provide the
      pivotal microenvironment for tumor development. The study aimed to evaluate the
      importance of the pancreatic stroma for tumor development. METHODS: Pancreatic
      tumor cells were implanted subcutaneously into green fluorescent protein
      transgenic mice, and stroma cells invading the tumors were identified through
      immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved
      with halofuginone, an inhibitor of TGFbeta/Smad3 signaling, alone or in
      combination with chemotherapy. The origin of tumor ECM was evaluated with species
      specific collagen I antibodies and in situ hybridization of collagen alpha1(I)
      gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen
      injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell
      infiltration and reduction of tumor ECM levels by halofuginone inhibited
      development of tumors derived from mouse and human pancreatic cancer cells.
      Halofuginone reduced the number only of stroma myofibroblasts expressing both
      contractile and collagen biosynthesis markers. Both stroma myofibroblasts and
      tumor cells generated ECM that contributes to tumor growth. Combination of
      treatments that inhibit stroma cell infiltration, cause apoptosis of
      myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that
      increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more
      efficacious than either treatment alone. More tumors developed in fibrotic than
      in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor
      development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma
      cells for tumor development presents potential new therapy targets, suggesting
      combination therapy against stroma and neoplastic cells as a treatment of choice.

PMID- 22848629
TI  - Effects of maternal basking and food quantity during gestation provide evidence
      for the selective advantage of matrotrophy in a viviparous lizard.
AB  - The evolution of matrotrophy (i.e., direct supply of nutrients by the mother
      during gestation) may be associated with high maternal energy availability during
      gestation. However, we lack knowledge about the selective advantages of
      matrotrophic viviparity (live-bearing) in reptiles. In reptiles, the interaction
      between body temperature and food intake affect maternal net energy gain. In the
      present study, we examined the effects of basking and food availability (2 by 2
      factorial design) during gestation on offspring phenotype in a matrotrophic
      viviparous lizard (Pseudemoia entrecasteauxii). Subsequently, we investigated if
      the maternal effects were context-dependent using offspring growth rate as an
      indicator of the adaptive significance of matrotrophy. Offspring were exposed
      either to the same thermal conditions as their mothers experienced or to thermal
      conditions different from those experienced by their mothers. We provide the
      first evidence that an interaction between maternal thermal and maternal food
      conditions during gestation strongly affects offspring phenotype, including date
      of birth, body size and performance ability, which affect offspring fitness.
      Offspring growth rate was dependent on offspring thermal conditions, but was not
      influenced by maternal effects or offspring sex. Matrotrophic viviparity provided
      gravid females with the means to enhance offspring fitness through greater
      energetic input to offspring when conditions allowed it (i.e., extended basking
      opportunity with high food availability). Therefore, we suggest that selective
      advantages of matrotrophic viviparity in P. entrecasteauxii may be associated
      with high maternal energy availability during gestation.

PMID- 22848628
TI  - Inhibition of sphingosine kinase-2 suppresses inflammation and attenuates graft
      injury after liver transplantation in rats.
AB  - Inflammation mediates/promotes graft injury after liver transplantation (LT).
      This study investigated the roles of sphingosine kinase-2 (SK2) in inflammation
      after LT. Liver grafts were stored in UW solution with and without ABC294640 (100
      uM), a selective inhibitor of SK2, before implantation. Hepatic sphingosine-1
      phosphate (S1P) levels increased ~4-fold after LT, which was blunted by 40% by
      ABC294640. Hepatic toll-like receptor-4 (TLR4) expression and nuclear factor
      kappaB (NF-kappaB) p65 subunit phosphorylation elevated substantially after
      transplantation. The pro-inflammatory cytokines/chemokines tumor necrosis factor
      alpha, interleukin-1beta and C-X-C motif chemokine 10 mRNAs increased 5.9-fold,
      6.1-fold and 16-fold, respectively following transplantation, while intrahepatic
      adhesion molecule-1 increased 5.7-fold and monocytes/macrophage and neutrophil
      infiltration and expansion of residential macrophage population increased 7.8
      13.4 fold, indicating enhanced inflammation. CD4+ T cell infiltration and
      interferon-gamma production also increased. ABC294640 blunted TLR4 expression by
      60%, NF-kappaB activation by 84%, proinflammatory cytokine/chemokine production
      by 45-72%, adhesion molecule expression by 54% and infiltration of
      monocytes/macrophages and neutrophils by 62-67%. ABC294640 also largely blocked
      CD4+ T cell infiltration and interferon-gamma production. Focal necrosis and
      apoptosis occurred after transplantation with serum alanine aminotransferase
      (ALT) reaching ~6000 U/L and serum total bilirubin elevating to ~1.5 mg/dL.
      Inhibition of SK2 by ABC294640 blunted necrosis by 57%, apoptosis by 74%, ALT
      release by ~68%, and hyperbilirubinemia by 74%. Most importantly, ABC294640 also
      increased survival from ~25% to ~85%. In conclusion, SK2 plays an important role
      in hepatic inflammation responses and graft injury after cold
      storage/transplantation and represents a new therapeutic target for liver graft
      failure.

PMID- 22848631
TI  - Fluctuating helical asymmetry and morphology of snails (Gastropoda) in divergent
      microhabitats at 'Evolution Canyons I and II,' Israel.
AB  - BACKGROUND: Developmental instability of shelled gastropods is measured as
      deviations from a perfect equiangular (logarithmic) spiral. We studied six
      species of gastropods at 'Evolution Canyons I and II' in Carmel and the Galilee
      Mountains, Israel, respectively. The xeric, south-facing, 'African' slopes and
      the mesic, north-facing, 'European' slopes have dramatically different
      microclimates and plant communities. Moreover, 'Evolution Canyon II' receives
      more rainfall than 'Evolution Canyon I.' METHODOLOGY/PRINCIPAL FINDINGS: We
      examined fluctuating asymmetry, rate of whorl expansion, shell height, and number
      of rotations of the body suture in six species of terrestrial snails from the two
      'Evolution Canyons.' The xeric 'African' slope should be more stressful to land
      snails than the 'European' slope, and 'Evolution Canyon I' should be more
      stressful than 'Evolution Canyon II.' Only Eopolita protensa jebusitica showed
      marginally significant differences in fluctuating helical asymmetry between the
      two slopes. Contrary to expectations, asymmetry was marginally greater on the
      'European' slope. Shells of Levantina spiriplana caesareana at 'Evolution Canyon
      I,' were smaller and more asymmetric than those at 'Evolution Canyon II.'
      Moreover, shell height and number of rotations of the suture were greater on the
      north-facing slopes of both canyons. CONCLUSIONS/SIGNIFICANCE: Our data is
      consistent with a trade-off between drought resistance and thermoregulation in
      snails; Levantina was significantly smaller on the 'African' slope, for
      increasing surface area and thermoregulation, while Eopolita was larger on the
      'African' slope, for reducing water evaporation. In addition, 'Evolution Canyon
      I' was more stressful than Evolution Canyon II' for Levantina.

PMID- 22848630
TI  - Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels
      during carcinogenic process in human colorectal tract.
AB  - BACKGROUND: Inflammatory reactions, known to promote tumor growth and invasion,
      have been found associated with colorectal carcinoma (CRC). Macrophages are the
      chief component of the inflammatory infiltration that occurs early in the
      progression from non-invasive to malignant tumor, with a switch from the pro
      inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are
      additional sources of inflammation-related molecules. The study aimed to
      evaluate, during colorectal carcinogenesis from benign to malignant phases: i)
      the trend of serum levels of IL-8, IL-6, TGFbeta1, VEGF and MMPs; ii) the
      parallel trend of CRP serum levels; iii) derangement of the principal TGFbeta1
      receptors (TGFbeta1RI/RII) in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS: 96
      patients with colon adenomas or CRC at different stages of progression, and 17
      controls, were recruited. Serum IL-8, IL-6, TGFbeta1, VEGF, MMPs and CRP levels
      were analyzed before endoscopy or surgery. TGFbeta1 receptors were evaluated in
      adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels
      of IL-8 in adenocarcinoma patients were increased from stage II, when also the
      enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two
      serum markers was found significantly correlated. Trend of serum CRP was also
      very similar to that of IL-8 and MMP-9, but just below statistical significance.
      TGFbeta1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no
      significant variations. In tissue specimens, TGFbeta1 receptors were already
      absent in about 50% of adenomas, and this percentage of missing receptors
      markedly increased in CRC stages III and IV. CONCLUSIONS: Combined quantification
      of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of
      inflammation-related processes during malignant phase of colorectal
      carcinogenesis, since these molecules remain within normal range in colorectal
      adenoma bearing patients, while consistently increase in the blood of CRC
      patients, even if from stage II only.

PMID- 22848632
TI  - Two-component systems are involved in the regulation of botulinum neurotoxin
      synthesis in Clostridium botulinum type A strain Hall.
AB  - Clostridium botulinum synthesizes a potent neurotoxin (BoNT) which associates
      with non-toxic proteins (ANTPs) to form complexes of various sizes. The bont and
      antp genes are clustered in two operons. In C. botulinum type A, bont/A and antp
      genes are expressed during the end of the exponential growth phase and the
      beginning of the stationary phase under the control of an alternative sigma
      factor encoded by botR/A, which is located between the two operons. In the genome
      of C. botulinum type A strain Hall, 30 gene pairs predicted to encode two
      component systems (TCSs) and 9 orphan regulatory genes have been identified.
      Therefore, 34 Hall isogenic antisense strains on predicted regulatory genes (29
      TCSs and 5 orphan regulatory genes) have been obtained by a mRNA antisense
      procedure. Two TCS isogenic antisense strains showed more rapid growth kinetics
      and reduced BoNT/A production than the control strain, as well as increased
      bacterial lysis and impairment of the bacterial cell wall structure. Three other
      TCS isogenic antisense strains induced a low level of BoNT/A and ANTP production.
      Interestingly, reduced expression of bont/A and antp genes was shown to be
      independent of botR/A. These results indicate that BoNT/A synthesis is under the
      control of a complex network of regulation including directly at least three
      TCSs.

PMID- 22848633
TI  - Histone methylation analysis and pathway predictions in chickens after MDV
      infection.
AB  - Marek's disease (MD) is a lymphoproliferative disease in chicken induced by
      Marek's disease virus (MDV). Although studies have focused on the genetic
      differences between the resistant and susceptible chicken, less is known about
      the role of epigenetic factors in MD. In this study, genome-wide histone
      modifications in the non-MHC-associated resistant and susceptible chicken lines
      were examined. We found that tri-methylation at histone H3 Lys4 (H3K4me3)
      enrichment is positively correlated with the expression of protein coding genes
      as well as microRNA (miRNA) genes, whereas tri-methylation at histone H3 Lys27
      (H3K27me3) exhibits a negative correlation. By identifying line-specific histone
      modifications in MDV infection, we found unique H3K4me3 islands in the resistant
      chicken activated genes, which are related to immune response and cell adhesion.
      Interestingly, we also found some miRNAs from unique H3K27me3 patterns in the
      susceptible chickens that targeted genes involved in 5-hydroxytryptamine (5-HT)
      receptor and adrenergic receptor pathways. In conclusion, dynamic line-specific
      histone modifications in response to MDV infection suggested that intrinsic
      epigenetic mechanisms may play a role in MD-resistance and -susceptibility.

PMID- 22848634
TI  - Hyperactivity in anorexia nervosa: warming up not just burning-off calories.
AB  - Excessive physical activity is a common feature in Anorexia Nervosa (AN) that
      interferes with the recovery process. Animal models have demonstrated that
      ambient temperature modulates physical activity in semi-starved animals. The aim
      of the present study was to assess the effect of ambient temperature on physical
      activity in AN patients in the acute phase of the illness. Thirty-seven patients
      with AN wore an accelerometer to measure physical activity within the first week
      of contacting a specialized eating disorder center. Standardized measures of
      anxiety, depression and eating disorder psychopathology were assessed.
      Corresponding daily values for ambient temperature were obtained from local
      meteorological stations. Ambient temperature was negatively correlated with
      physical activity (p = -.405) and was the only variable that accounted for a
      significant portion of the variance in physical activity (p = .034). Consistent
      with recent research with an analogous animal model of the disorder, our findings
      suggest that ambient temperature is a critical factor contributing to the
      expression of excessive physical activity levels in AN. Keeping patients warm may
      prove to be a beneficial treatment option for this symptom.

PMID- 22848635
TI  - Expressional changes in cerebrovascular receptors after experimental transient
      forebrain ischemia.
AB  - BACKGROUND: Global ischemic stroke is one of the most prominent consequences of
      cardiac arrest, since the diminished blood flow to the brain results in cell
      damage and sometimes permanently impaired neurological function. The post-arrest
      period is often characterised by cerebral hypoperfusion due to subacute
      hemodynamic disturbances, the pathophysiology of which are poorly understood. In
      two other types of stroke, focal ischemic stroke and subarachnoid hemorrhage, it
      has earlier been demonstrated that the expression of certain vasoconstrictor
      receptors is increased in cerebral arteries several days after the insult, a
      phenomenon that leads to increased contraction of cerebral arteries, reduced
      perfusion of the affected area and worsened ischemic damage. Based on these
      findings, the aim of the present study was to investigate if transient global
      cerebral ischemia is associated with upregulation of vasoconstrictive endothelin
      and 5-hydroxytryptamine receptors in cerebral arteries. Experimental transient
      forebrain ischemia of varying durations was induced in male wistar rats, followed
      by reperfusion for 48 hours. Neurological function was assessed daily by three
      different tests and cerebrovascular expression and contractile function of
      endothelin and 5-hydroxytryptamine receptors were evaluated by wire myography,
      immunohistochemistry and western blotting. RESULTS: Transient forebrain ischemia
      induced neurological deficits as well as functional upregulation of
      vasoconstrictive ET(B) and 5-HT(1B) receptors in cerebral arteries supplying mid-
      and forebrain regions. No receptor upregulation was seen in arteries supplying
      the hindbrain. Immunohistochemical stainings and western blotting demonstrated
      expressional upregulation of these receptor subtypes in the mid- and forebrain
      arteries and confirmed that the receptors were located in the smooth muscle layer
      of the cerebral arteries. CONCLUSIONS: This study reveals a new
      pathophysiological aspect of global ischemic stroke, namely expressional
      upregulation of vasoconstrictor receptors in cerebral arteries two days after the
      insult, which might contribute to cerebral hypoperfusion and delayed neuronal
      damage after cardiac arrest.

PMID- 22848636
TI  - Association between single nucleotide polymorphisms in ERCC4 and risk of squamous
      cell carcinoma of the head and neck.
AB  - BACKGROUND: Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays
      an important role in nucleotide excision repair and participates in removal of
      DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide
      polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer
      susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: In this case-control study, we
      evaluated associations of four selected potentially functional SNPs in ERCC4 with
      risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non
      Hispanic white patients with SCCHN and 1,046 cancer-free matched controls. We
      found that the variant GG genotype of rs2276466 was significantly associated with
      a decreased risk of SCCHN (OR = 0.69, 95% CI 0.50-0.96), and that the variant TT
      genotype of rs3136038 showed a borderline significant decreased risk with SCCHN
      (OR = 0.76, 95% CI: 0.58-1.01) in the recessive model. Such protective effects
      were more evident in oropharyngeal cancer (OR = 0.61, 95% CI: 0.40-0.92 for
      rs2276466; OR = 0.69, 95% CI: 0.48-0.98 for rs3136038). No significant
      associations were found for the other two SNPs (rs1800067 and rs1799798). In
      addition, individuals with the rs2276466 GG or with the rs3136038 TT genotypes
      had higher levels of ERCC4 mRNA expression than those with the corresponding wild
      type genotypes in 90 Epstein-Barr virus-transformed lymphoblastoid cell lines
      derived from Caucasians. CONCLUSIONS: These results suggest that these two SNPs
      (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN
      susceptibility. However, our findings need to be replicated in further large
      epidemiological and functional studies.

PMID- 22848637
TI  - Identifying responsive modules by mathematical programming: an application to
      budding yeast cell cycle.
AB  - High-throughput biological data offer an unprecedented opportunity to fully
      characterize biological processes. However, how to extract meaningful biological
      information from these datasets is a significant challenge. Recently, pathway
      based analysis has gained much progress in identifying biomarkers for some
      phenotypes. Nevertheless, these so-called pathway-based methods are mainly
      individual-gene-based or molecule-complex-based analyses. In this paper, we
      developed a novel module-based method to reveal causal or dependent relations
      between network modules and biological phenotypes by integrating both gene
      expression data and protein-protein interaction network. Specifically, we first
      formulated the identification problem of the responsive modules underlying
      biological phenotypes as a mathematical programming model by exploiting phenotype
      difference, which can also be viewed as a multi-classification problem. Then, we
      applied it to study cell-cycle process of budding yeast from microarray data
      based on our biological experiments, and identified important phenotype- and
      transition-based responsive modules for different stages of cell-cycle process.
      The resulting responsive modules provide new insight into the regulation
      mechanisms of cell-cycle process from a network viewpoint. Moreover, the
      identification of transition modules provides a new way to study dynamical
      processes at a functional module level. In particular, we found that the
      dysfunction of a well-known module and two new modules may directly result in
      cell cycle arresting at S phase. In addition to our biological experiments, the
      identified responsive modules were also validated by two independent datasets on
      budding yeast cell cycle.

PMID- 22848638
TI  - Minocycline inhibits alkali burn-induced corneal neovascularization in mice.
AB  - The purpose of this study was to investigate the effects of minocycline on alkali
      burn-induced corneal neovascularization (CNV). A total of 105 mice treated with
      alkali burns were randomly divided into three groups to receive intraperitoneal
      injections of either phosphate buffered saline (PBS) or minocycline twice a day
      (60 mg/kg or 30 mg/kg) for 14 consecutive days. The area of CNV and corneal
      epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day
      14, a histopathological examination was performed to assess morphological change
      and the infiltration of polymorphonuclear neutrophils (PMNs). The mRNA expression
      levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs),
      basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMPs),
      interleukin-1alpha, 1beta, 6 (IL-1alpha, IL-1beta, IL-6) were analyzed using real
      time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9
      proteins was determined by gelatin zymography. In addition, enzyme-linked
      immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL
      1beta and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly
      enhanced the recovery of the corneal epithelial defects more than PBS did. There
      were significant decreases of corneal neovascularization in the group of high
      dosage minocycline compared with the control group at all checkpoints. On day 14,
      the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2,
      bFGF, IL-1beta, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of
      VEGFR2, MMP-2, -9, IL-1beta, IL-6 in the corneas were down-regulated with the use
      of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal
      injection of minocycline (60 mg/kg b.i.d.) can significantly inhibit alkali burn
      induced corneal neovascularization in mice, possibly by accelerating corneal
      wound healing and by reducing the production of angiogenic factors, inflammatory
      cytokines and MMPs.

PMID- 22848639
TI  - Effects of exogenous cholecystokinin octapeptide on acquisition of naloxone
      precipitated withdrawal induced conditioned place aversion in rats.
AB  - Cholecystokinin octapeptide (CCK-8), a gut-brain peptide, regulates a variety of
      physiological behavioral processes. Previously, we reported that exogenous CCK-8
      attenuated morphine-induced conditioned place preference, but the possible
      effects of CCK-8 on aversively motivated drug seeking remained unclear. To
      investigate the effects of endogenous and exogenous CCK on negative components of
      morphine withdrawal, we evaluated the effects of CCK receptor antagonists and CCK
      8 on the naloxone-precipitated withdrawal-induced conditioned place aversion
      (CPA). The results showed that CCK2 receptor antagonist (LY-288,513, 10 ug,
      i.c.v.), but not CCK1 receptor antagonist (L-364,718, 10 ug, i.c.v.), inhibited
      the acquisition of CPA when given prior to naloxone (0.3 mg/kg) administration in
      morphine-dependent rats. Similarly, CCK-8 (0.1-1 ug, i.c.v.) significantly
      attenuated naloxone-precipitated withdrawal-induced CPA, and this inhibitory
      function was blocked by co-injection with L-364,718. Microinjection of L-364,718,
      LY-288,513 or CCK-8 to saline pretreated rats produced neither a conditioned
      preference nor aversion, and the induction of CPA by CCK-8 itself after morphine
      pretreatments was not significant. Our study identifies a different role of CCK1
      and CCK2 receptors in negative affective components of morphine abstinence and an
      inhibitory effect of exogenous CCK-8 on naloxone-precipitated withdrawal-induced
      CPA via CCK1 receptor.

PMID- 22848640
TI  - Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor
      degradation.
AB  - Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of
      hepatic low-density lipoprotein receptor (LDLR). Deletion of PCSK9, and loss-of
      function mutants in humans result in lower levels of circulating LDL-cholesterol
      and a strong protection against coronary heart disease. Accordingly, the quest
      for PCSK9 inhibitors has major clinical implications. We have previously
      identified annexin A2 (AnxA2) as an endogenous binding partner and functional
      inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition
      and lipid metabolism in vivo. Plasma analyses of AnxA2(-/-) mice revealed: i) a
      ~1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or
      HDLs, and ii) a ~2-fold increase in circulating PCSK9 levels. Western blotting
      and immunohistochemistry of AnxA2(-/-) tissues revealed that the LDLR was
      decreased by ~50% in extrahepatic tissues, such as adrenals and colon. We also
      show that AnxA2-derived synthetic peptides block the PCSK9=LDLR interaction in
      vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR
      protein levels in vivo. These results suggest that AnxA2 acts as an endogenous
      regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we
      identified an AnxA2 coding polymorphism, V98L, that correlates with lower
      circulating levels of PCSK9 thereby extending our results on the physiological
      role of AnxA2 in humans.

PMID- 22848641
TI  - 454 Transcriptome sequencing suggests a role for two-component signalling in
      cellularization and differentiation of barley endosperm transfer cells.
AB  - BACKGROUND: Cell specification and differentiation in the endosperm of cereals
      starts at the maternal-filial boundary and generates the endosperm transfer cells
      (ETCs). Besides the importance in assimilate transfer, ETCs are proposed to play
      an essential role in the regulation of endosperm differentiation by affecting
      development of proximate endosperm tissues. We attempted to identify signalling
      elements involved in early endosperm differentiation by using a combination of
      laser-assisted microdissection and 454 transcriptome sequencing. PRINCIPAL
      FINDINGS: 454 sequencing of the differentiating ETC region from the syncytial
      state until functionality in transfer processes captured a high proportion of
      novel transcripts which are not available in existing barley EST databases.
      Intriguingly, the ETC-transcriptome showed a high abundance of elements of the
      two-component signalling (TCS) system suggesting an outstanding role in ETC
      differentiation. All components and subfamilies of the TCS, including distinct
      kinds of membrane-bound receptors, have been identified to be expressed in ETCs.
      The TCS system represents an ancient signal transduction system firstly
      discovered in bacteria and has previously been shown to be co-opted by
      eukaryotes, like fungi and plants, whereas in animals and humans this signalling
      route does not exist. Transcript profiling of TCS elements by qRT-PCR suggested
      pivotal roles for specific phosphorelays activated in a coordinated time flow
      during ETC cellularization and differentiation. ETC-specificity of
      transcriptionally activated TCS phosphorelays was assessed for early
      differentiation and cellularization contrasting to an extension of expression to
      other grain tissues at the beginning of ETC maturation. Features of candidate
      genes of distinct phosphorelays and transcriptional activation of genes
      putatively implicated in hormone signalling pathways hint at a crosstalk of
      hormonal influences, putatively ABA and ethylene, and TCS signalling.
      SIGNIFICANCE: Our findings suggest an integral function for the TCS in ETC
      differentiation possibly coupled to sequent hormonal regulation by ABA and
      ethylene.

PMID- 22848642
TI  - Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK
      cells cytotoxicity by up-regulating expression of SOCS3.
AB  - BACKGROUND: Decidual stromal cells (DSCs) are of particular importance due to
      their pleiotropic functions during pregnancy. Although previous research has
      demonstrated that DSCs participated in the regulation of immune cells during
      pregnancy, the crosstalk between DSCs and NK cells has not been fully elucidated.
      To address this issue, we investigated the effect of DSCs on perforin expression
      in CD56(+) NK cells and explored the underlying mechanism. METHODOLOGY/PRINCIPAL
      FINDINGS: Flow cytometry analysis showed perforin production in NK cells was
      attenuated by DSC media, and it was further suppressed by media from DSCs
      pretreated with lipopolysaccharide (LPS). However, the expression of granzyme A
      and apoptosis of NK cells were not influenced by DSC media. ELISA assays to
      detect cytokine production indicated that monocyte chemoattractant protein-1 (MCP
      1) in the supernatant of DSCs conditioned culture significantly increased after
      LPS stimulation. The inhibitory effect of DSC media on perforin was abolished by
      the administration of anti-MCP-1 neutralizing antibody. Notably, reduced perforin
      expression attenuated the cytotoxic potential of CD56(+) NK cells to K562 cells.
      Moreover, Suppressor of cytokine signaling 3 (SOCS3) expression in NK cells was
      enhanced by treatment with MCP-1, as measured by RT-PCR and western blot.
      Interestingly, MCP-1-induced perforin expression was partly abolished by the
      siRNA induced SOCS3 knockdown. Western blot analysis suggested that both NF
      kappaB and ERK/MAPKs pathway were involved in the LPS-induced upregulation of MCP
      1 in DSCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that LPS induces
      upregulation of MCP-1 in DSCs, which may play a critical role in inhibiting the
      cytotoxicity of NK cells partly by promoting SOCS3 expression. These findings
      suggest that the crosstalk between DSCs and NK cells may be crucial to maintain
      pregnancy homeostasis.

PMID- 22848643
TI  - Allocentric or craniocentric representation of acoustic space: an
      electrotomography study using mismatch negativity.
AB  - The world around us appears stable in spite of our constantly moving head, eyes,
      and body. How this is achieved by our brain is hardly understood and even less so
      in the auditory domain. Using electroencephalography and the so-called mismatch
      negativity, we investigated whether auditory space is encoded in an allocentric
      (referenced to the environment) or craniocentric representation (referenced to
      the head). Fourteen subjects were presented with noise bursts from loudspeakers
      in an anechoic environment. Occasionally, subjects were cued to rotate their
      heads and a deviant sound burst occurred, that deviated from the preceding
      standard stimulus either in terms of an allocentric or craniocentric frame of
      reference. We observed a significant mismatch negativity, i.e., a more negative
      response to deviants with reference to standard stimuli from about 136 to 188 ms
      after stimulus onset in the craniocentric deviant condition only. Distributed
      source modeling with sLORETA revealed an involvement of lateral superior temporal
      gyrus and inferior parietal lobule in the underlying neural processes. These
      findings suggested a craniocentric, rather than allocentric, representation of
      auditory space at the level of the mismatch negativity.

PMID- 22848645
TI  - Armament imbalances: match and mismatch in plant-pollinator traits of highly
      specialized long-spurred orchids.
AB  - BACKGROUND: Some species of long-spurred orchids achieve pollination by a close
      association with long-tongued hawkmoths. Among them, several Habenaria species
      present specialized mechanisms, where pollination success depends on the
      attachment of pollinaria onto the heads of hawkmoths with very long proboscises.
      However, in the Neotropical region such moths are less abundant than their
      shorter-tongued relatives and are also prone to population fluctuations. Both
      factors may give rise to differences in pollinator-mediated selection on floral
      traits through time and space. METHODOLOGY/PRINCIPAL FINDINGS: We characterized
      hawkmoth assemblages and estimated phenotypic selection gradients on orchid spur
      lengths in populations of three South American Habenaria species. We examined the
      match between hawkmoth proboscis and flower spur lengths to determine whether
      pollinators may act as selective agents on flower morphology. We found
      significant directional selection on spur length only in Habenaria gourlieana,
      where most pollinators had proboscises longer than the mean of orchid spur
      length. CONCLUSIONS/SIGNIFICANCE: Phenotypic selection is dependent on the mutual
      match between pollinator and flower morphologies. However, our findings indicate
      that pollinator-mediated selection may vary through time and space according to
      local variations in pollinator assemblages.

PMID- 22848644
TI  - Longitudinal deformation-based morphometry reveals spatio-temporal dynamics of
      brain volume changes in patients with corticobasal syndrome.
AB  - BACKGROUND/OBJECTIVE: Corticobasal syndrome (CBS) is a rare neurodegenerative
      disorder characterized by a progressive and asymmetric manifestation of cortical
      and basal-ganglia symptoms of different origin. The spatio-temporal dynamics of
      cerebral atrophy in CBS is barely known. This study aimed to longitudinally
      quantify the individual dynamics of brain volume changes in patients with CBS as
      compared to healthy controls. METHODS: We used deformation-field-based
      morphometry (DFM) to study volumetric changes of each individual brain in short
      intervals of a few months. DFM enabled the quantitative analysis of local volume
      changes without predefining regions of interest in MR images of 6 patients with
      CBS and 11 matched healthy controls. A total of 64 whole brain 3D-MR-scans were
      acquired two to eight times over periods of 14 to 26 months. Based on repeated
      registrations of MR observations to the initial scan, maps of local volume ratio
      changes were computed. RESULTS: Compared to controls patients showed significant
      and increasing volume loss over time in premotor and primary-motor-cortices,
      somatosensory area 3a, superior parietal areas BA 5/7, and corticospinal tract.
      Furthermore, significant and asymmetric atrophy was identified in the caudate
      nucleus head, putamen, pallidum, motor-thalamus and substantia nigra. Temporal
      lobe was affected in those patients who presented progressive cognitive
      impairment. CONCLUSIONS: The analysis revealed localized, pathological changes in
      brains of patients with CBS, which differed significantly from those occurring
      during aging in healthy controls. As compared to age- and sex-matched controls,
      brains of CBS patients showed a common degenerating neural network comprising the
      motor circuit with basal ganglia and motor thalamic nuclei as well as the
      premotor and primary-motor-cortex.

PMID- 22848646
TI  - Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes
      to preeclampsia in humans and mice.
AB  - Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome characterized by
      excessive maternal immune system activation, inflammation, and endothelial
      dysfunction. Toll-like receptor (TLR) 3 activation by double-stranded RNA (dsRNA)
      and TLR7/8 activation by single-stranded RNA (ssRNA) expressed by viruses and/or
      released from necrotic cells initiates a pro-inflammatory immune response;
      however it is unknown whether viral/endogenous RNA is a key initiating signal
      that contributes to the development of PE. We hypothesized that TLR3/7/8
      activation will be evident in placentas of women with PE, and sufficient to
      induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of
      TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to
      normotensive women. Treatment of human trophoblasts with the TLR3 agonist
      polyinosine-polycytidylic acid (poly I:C), the TLR7-specific agonist imiquimod (R
      837), or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels.
      Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent
      hypertension, endothelial dysfunction, splenomegaly, and placental inflammation.
      These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a
      key role in the development of PE.

PMID- 22848647
TI  - Pasture names with Romance and Slavic roots facilitate dissection of Y chromosome
      variation in an exclusively German-speaking alpine region.
AB  - The small alpine district of East Tyrol (Austria) has an exceptional demographic
      history. It was contemporaneously inhabited by members of the Romance, the Slavic
      and the Germanic language groups for centuries. Since the Late Middle Ages,
      however, the population of the principally agrarian-oriented area is solely
      Germanic speaking. Historic facts about East Tyrol's colonization are rare, but
      spatial density-distribution analysis based on the etymology of place-names has
      facilitated accurate spatial mapping of the various language groups' former
      settlement regions. To test for present-day Y chromosome population substructure,
      molecular genetic data were compared to the information attained by the
      linguistic analysis of pasture names. The linguistic data were used for
      subdividing East Tyrol into two regions of former Romance (A) and Slavic (B)
      settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y
      chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y
      SNPs). Analysis of the probands' surnames revealed no evidence for spatial
      genetic structuring. Also, spatial autocorrelation analysis did not indicate
      significant correlation between genetic (Y-STR haplotypes) and geographic
      distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but
      constituted one of the most frequent haplogroups in region B. The R-M343 (R1b)
      clade showed a marked and complementary frequency distribution pattern in these
      two regions. To further test East Tyrol's modern Y-chromosomal landscape for
      geographic patterning attributable to the early history of settlement in this
      alpine area, principal coordinates analysis was performed. The Y-STR haplotypes
      from region A clearly clustered with those of Romance reference populations and
      the samples from region B matched best with Germanic speaking reference
      populations. The combined use of onomastic and molecular genetic data revealed
      and mapped the marked structuring of the distribution of Y chromosomes in an
      alpine region that has been culturally homogeneous for centuries.

PMID- 22848648
TI  - Fungal farming in a non-social beetle.
AB  - Culturing of microbes for food production, called cultivation mutualism, has been
      well-documented from eusocial and subsocial insects such as ants, termites and
      ambrosia beetles, but poorly described from solitary, non-social insects. Here we
      report a fungal farming in a non-social lizard beetle Doubledaya bucculenta
      (Coleoptera: Erotylidae: Languriinae), which entails development of a special
      female structure for fungal storage/inoculation, so-called mycangium, and also
      obligate dependence of the insect on the fungal associate. Adult females of D.
      bucculenta bore a hole on a recently-dead bamboo culm with their specialized
      mandibles, lay an egg into the internode cavity, and plug the hole with bamboo
      fibres. We found that the inner wall of the bamboo internode harboring a larva is
      always covered with a white fungal layer. A specific Saccharomycetes yeast,
      Wickerhamomyces anomalus ( = Pichia anomala), was consistently isolated from the
      inner wall of the bamboo internodes and also from the body surface of the larvae.
      Histological examination of the ovipositor of adult females revealed an
      exoskeletal pocket on the eighth abdominal segment. The putative mycangium
      contained yeast cells, and W. anomalus was repeatedly detected from the symbiotic
      organ. When first instar larvae were placed on culture media inoculated with W.
      anomalus, they grew and developed normally to adulthood. By contrast, first
      instar larvae placed on either sterile culture media or autoclaved strips of
      bamboo inner wall exhibited arrested growth at the second instar, and addition of
      W. anomalus to the media resumed growth and development of the larvae. These
      results strongly suggest a mutualistic nature of the D. bucculenta-W. anomalus
      association with morphological specialization and physiological dependence. Based
      on these results, we compare the fungal farming of D. bucculenta with those of
      social and subsocial insects, and discuss ecological factors relevant to the
      evolution of fungal farming in a non-social insect.

PMID- 22848649
TI  - Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2
      influenza viruses.
AB  - H3N2 influenza viruses have now circulated in the human population for 43 years
      since the pandemic of 1968, accumulating sequence changes in the hemagglutinin
      (HA) and neuraminidase (NA) that are believed to be predominantly due to
      selection for escape from antibodies. Examination of mutations that persist and
      accumulate led to identification of antigenically significant mutations that are
      contained in five antigenic sites (A-E) mapped on to the H3 HA. In early H3N2
      isolates, antigenic site A appeared to be dominant while in the 1990s site B
      seemed more important. To obtain experimental evidence for dominance of antigenic
      sites on modern H3 HAs, we have measured antibodies in plasma of human subjects
      who received the 2006-07 trivalent subunit influenza vaccine (H3 component
      A/Wisconsin/67/05) or the 2008-09 formulation (H3 component A/Uruguay/716/07).
      Plasmas were tested against expressed HA of Wisconsin-like influenza
      A/Oklahoma/309/06 and site-directed mutants in antigenic site A (NNES121-124ITEG,
      N126T, N133D, TSSS135-138GSNA, K140I, RSNNS142-146PGSG), and antigenic site B
      (HL156-157KS, KFK158-160GST, NDQI189-192QEQT, A196V). "Native ELISA" analysis and
      escape mutant selection with two human monoclonal antibodies demonstrated that
      antibody E05 binds to antigenic site A and 1_C02 binds to site B. We find that
      most individuals, after vaccination in seasons 2006-07 and/or 2008-09, showed
      dominance of antigenic site B recognition over antigenic site A. A minority
      showed dominance of site A in 2006 but these were reduced in 2008 when the
      vaccine virus had a site A mutation. A better understanding of immunodominance
      may allow prediction of future antigenic drift and assist in vaccine strain
      selection.

PMID- 22848650
TI  - A smell that causes seizure.
AB  - In mammals, odorants are detected by a large family of receptors that are each
      expressed in just a small subset of olfactory sensory neurons (OSNs). Here we
      describe a strain of transgenic mice engineered to express an octanal receptor in
      almost all OSNs. Remarkably, octanal triggered a striking and involuntary
      phenotype in these animals, with passive exposure regularly inducing seizures.
      Octanal exposure invariably resulted in widespread activation of OSNs but
      interestingly seizures only occurred in 30-40% of trials. We hypothesized that
      this reflects the need for the olfactory system to filter strong but slowly
      changing backgrounds from salient signals. Therefore we used an olfactometer to
      control octanal delivery and demonstrated suppression of responses whenever this
      odorant is delivered slowly. By contrast, rapid exposure of the mice to octanal
      induced seizure in every trial. Our results expose new details of olfactory
      processing and provide a robust and non-invasive platform for studying epilepsy.

PMID- 22848651
TI  - Empirical validation of pooled whole genome population re-sequencing in
      Drosophila melanogaster.
AB  - The sequencing of pooled non-barcoded individuals is an inexpensive and efficient
      means of assessing genome-wide population allele frequencies, yet its accuracy
      has not been thoroughly tested. We assessed the accuracy of this approach on
      whole, complex eukaryotic genomes by resequencing pools of largely isogenic,
      individually sequenced Drosophila melanogaster strains. We called SNPs in the
      pooled data and estimated false positive and false negative rates using the SNPs
      called in individual strain as a reference. We also estimated allele frequency of
      the SNPs using "pooled" data and compared them with "true" frequencies taken from
      the estimates in the individual strains. We demonstrate that pooled sequencing
      provides a faithful estimate of population allele frequency with the error well
      approximated by binomial sampling, and is a reliable means of novel SNP discovery
      with low false positive rates. However, a sufficient number of strains should be
      used in the pooling because variation in the amount of DNA derived from
      individual strains is a substantial source of noise when the number of pooled
      strains is low. Our results and analysis confirm that pooled sequencing is a very
      powerful and cost-effective technique for assessing of patterns of sequence
      variation in populations on genome-wide scales, and is applicable to any dataset
      where sequencing individuals or individual cells is impossible, difficult, time
      consuming, or expensive.

PMID- 22848652
TI  - Genes associated with retinitis pigmentosa and allied diseases are frequently
      mutated in the general population.
AB  - BACKGROUND: Retinitis pigmentosa and other hereditary retinal degenerations (HRD)
      are rare genetic diseases leading to progressive blindness. Recessive HRD are
      caused by mutations in more than 100 different genes. Laws of population genetics
      predict that, on a purely theoretical ground, such a high number of genes should
      translate into an extremely elevated frequency of unaffected carriers of
      mutations. In this study we estimate the proportion of these individuals within
      the general population, via the analyses of data from whole-genome sequencing.
      METHODOLOGY/PRINCIPAL FINDINGS: We screened complete and high-quality genome
      sequences from 46 control individuals from various world populations for HRD
      mutations, using bioinformatic tools developed in-house. All mutations detected
      in silico were validated by Sanger sequencing. We identified clear-cut, null
      recessive HRD mutations in 10 out of the 46 unaffected individuals analyzed
      (~22%). CONCLUSIONS/SIGNIFICANCE: Based on our data, approximately one in 4-5
      individuals from the general population may be a carrier of null mutations that
      are responsible for HRD. This would be the highest mutation carrier frequency so
      far measured for a class of Mendelian disorders, especially considering that
      missenses and other forms of pathogenic changes were not included in our
      assessment. Among other things, our results indicate that the risk for a
      consanguineous couple of generating a child with a blinding disease is
      particularly high, compared to other genetic conditions.

PMID- 22848653
TI  - Phylodynamics of HIV-1 subtype C epidemic in east Africa.
AB  - The HIV-1 subtype C accounts for an important fraction of HIV infections in east
      Africa, but little is known about the genetic characteristics and evolutionary
      history of this epidemic. Here we reconstruct the origin and spatiotemporal
      dynamics of the major HIV-1 subtype C clades circulating in east Africa. A large
      number (n = 1,981) of subtype C pol sequences were retrieved from public
      databases to explore relationships between strains from the east, southern and
      central African regions. Maximum-likelihood phylogenetic analysis of those
      sequences revealed that most (>70%) strains from east Africa segregated in a
      single regional-specific monophyletic group, here called C(EA). A second major
      Ethiopian subtype C lineage and a large collection of minor Kenyan and Tanzanian
      subtype C clades of southern African origin were also detected. A bayesian
      coalescent-based method was then used to reconstruct evolutionary parameters and
      migration pathways of the C(EA) African lineage. This analysis indicates that the
      C(EA) clade most probably originated in Burundi around the early 1960s, and later
      spread to Ethiopia, Kenya, Tanzania and Uganda, giving rise to major country
      specific monophyletic sub-clusters between the early 1970s and early 1980s. The
      results presented here demonstrate that a substantial proportion of subtype C
      infections in east Africa resulted from dissemination of a single HIV local
      variant, probably originated in Burundi during the 1960s. Burundi was the most
      important hub of dissemination of that subtype C clade in east Africa, fueling
      the origin of new local epidemics in Ethiopia, Kenya, Tanzania and Uganda.
      Subtype C lineages of southern African origin have also been introduced in east
      Africa, but seem to have had a much more restricted spread.

PMID- 22848654
TI  - NR2C in the thalamic reticular nucleus; effects of the NR2C knockout.
AB  - NMDAR antagonists can evoke delta frequency bursting in the nucleus reticularis
      of the thalamus (nRT). The mechanism of this oscillation was determined;
      antagonist blocks an NR2C-like conductance that has low Mg block at resting
      potential and thus can contribute a resting inward current in response to ambient
      glutamate. Block of this current hyperpolarizes the cell, deinactivating T-type
      Ca channels and thus triggering delta frequency bursting. The basis for assuming
      a NR2C-like conductance was that (1) transcripts for NR2C are abundant in the
      thalamus and (2) the current-voltage curve of the synaptically evoked NMDAR
      current has the low rectification characteristic of NR2C. In the current study,
      we have sought to determine whether the channels that generate the NMDAR current
      are NR2C-like or are actually comprised of receptors containing NR2C. We studied
      the current-voltage curve of synaptically evoked NMDAR current in the nRT of NR2C
      knockout mice. In wild-type mice, the current was weakly voltage dependent, as
      previously observed in rats. This weak rectification was absent in NR2C KO mice.
      In contrast, NR2C KO had no effect on the strongly rectifying NMDAR current in
      pyramidal cells of the prefrontal cortex. These results demonstrate that the low
      rectification normally observed in the nRT is due to NR2C.

PMID- 22848655
TI  - Crystal structure of the Sema-PSI extracellular domain of human RON receptor
      tyrosine kinase.
AB  - Human RON (Recepteur d'Origine Nantais) receptor tyrosine kinase is a cell
      surface receptor for Macrophage Stimulating Protein (MSP). RON mediates signal
      transduction pathways that regulate cell adhesion, invasion, motility and
      apoptosis processes. Elevated levels of RON and its alternatively spliced
      variants are implicated in the progression and metastasis of tumor cells. The
      binding of MSP alpha/beta heterodimer to the extracellular region of RON receptor
      induces receptor dimerization and activation by autophosphorylation of the
      intracellular kinase domains. The ectodomain of RON, containing the ligand
      recognition and dimerization domains, is composed of a semaphorin (Sema), Plexins
      Semaphorins-Integrins domain (PSI), and four Immunoglobulins-Plexins
      Transcription factor (IPT) domains. High affinity association between MSP and RON
      is mediated by the interaction between MSP beta-chain and RON Sema, although RON
      activation requires intact RON and MSP proteins. Here, we report the structure of
      RON Sema-PSI domains at 1.85 A resolution. RON Sema domain adopts a seven-bladed
      beta-propeller fold, followed by disulfide bond rich, cysteine-knot PSI motif.
      Comparison with the homologous Met receptor tyrosine kinase reveals that RON Sema
      PSI contains distinguishing secondary structural features. These define the
      receptors' exclusive selectivity towards their respective ligands, RON for MSP
      and Met for HGF. The RON Sema-PSI crystal packing generates a homodimer with
      interface formed by the Sema domain. Mapping of the dimer interface using the RON
      homology to Met, MSP homology to Hepatocyte Growth Factor (HGF), and the
      structure of the Met/HGF complex shows the dimer interface overlapping with the
      putative MSPbeta binding site. The crystallographically determined RON Sema-PSI
      homodimer may represent the dimer assembly that occurs during ligand-independent
      receptor activation and/or the inhibition of the constitutive activity of
      RONDelta160 splice variant by the soluble RON splice variant, RONDelta85.

PMID- 22848656
TI  - Reduced intestinal tumorigenesis in APCmin mice lacking melanin-concentrating
      hormone.
AB  - BACKGROUND: Melanin-concentrating hormone (MCH) is an evolutionary conserved
      hypothalamic neuropeptide that in mammals primarily regulates appetite and energy
      balance. We have recently identified a novel role for MCH in intestinal
      inflammation by demonstrating attenuated experimental colitis in MCH deficient
      mice or wild type mice treated with an anti-MCH antibody. Therefore, targeting
      MCH has been proposed for the treatment of inflammatory bowel disease. Given the
      link between chronic intestinal inflammation and colorectal cancer, in the
      present study we sought to investigate whether blocking MCH might have effects on
      intestinal tumorigenesis that are independent of inflammation. METHODOLOGY: Tumor
      development was evaluated in MCH-deficient mice crossed to the APCmin mice which
      develop spontaneously intestinal adenomas. A different cohort of MCH-/- and
      MCH+/+ mice in the APCmin background was treated with dextran sodium sulphate
      (DSS) to induce inflammation-dependent colorectal tumors. In Caco2 human
      colorectal adenocarcinoma cells, the role of MCH on cell survival, proliferation
      and apoptosis was investigated. RESULTS: APCmin mice lacking MCH developed fewer,
      smaller and less dysplastic tumors in the intestine and colon which at the
      molecular level are characterized by attenuated activation of the wnt/beta
      catenin signaling pathway and increased apoptotic indices. Form a mechanistic
      point of view, MCH increased the survival of colonic adenocarcinoma Caco2 cells
      via inhibiting apoptosis, consistent with the mouse studies. CONCLUSION: In
      addition to modulating inflammation, MCH was found to promote intestinal
      tumorigenesis at least in part by inhibiting epithelial cell apoptosis. Thereby,
      blocking MCH as a therapeutic approach is expected to decrease the risk for
      colorectal cancer.

PMID- 22848657
TI  - Thermotaxis of human sperm cells in extraordinarily shallow temperature gradients
      over a wide range.
AB  - On the basis of the finding that capacitated (ready to fertilize) rabbit and
      human spermatozoa swim towards warmer temperatures by directing their movement
      along a temperature gradient, sperm thermotaxis has been proposed to be one of
      the processes guiding these spermatozoa to the fertilization site. Although the
      molecular mechanism underlying sperm thermotaxis is gradually being revealed,
      basic questions related to this process are still open. Here, employing human
      spermatozoa, we addressed the questions of how wide the temperature range of
      thermotaxis is, whether this range includes an optimal temperature or whether
      spermatozoa generally prefer swimming towards warmer temperatures, whether or not
      they can sense and respond to descending temperature gradients, and what the
      minimal temperature gradient is to which they can thermotactically respond. We
      found that human spermatozoa can respond thermotactically within a wide
      temperature range (at least 29-41 degrees C), that within this range they
      preferentially accumulate in warmer temperatures rather than at a single
      specific, preferred temperature, that they can respond to both ascending and
      descending temperature gradients, and that they can sense and thermotactically
      respond to temperature gradients as low as <0.014 degrees C/mm. This temperature
      gradient is astonishingly low because it means that as a spermatozoon swims
      through its entire body length (46 um) it can sense and respond to a temperature
      difference of <0.0006 degrees C. The significance of this surprisingly high
      temperature sensitivity is discussed.

PMID- 22848658
TI  - Haploinsufficiency for translation elongation factor eEF1A2 in aged mouse muscle
      and neurons is compatible with normal function.
AB  - Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons.
      Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype "wasted"
      (wst). Mice homozygous for the wasted mutation die of muscle wasting and
      neurodegeneration at four weeks post-natal. Although the mutation is said to be
      recessive, aged heterozygous mice have never been examined in detail; a number of
      other mouse models of motor neuron degeneration have recently been shown to have
      similar, albeit less severe, phenotypic abnormalities in the heterozygous state.
      We therefore examined the effects of ageing on a cohort of heterozygous +/wst
      mice and control mice, in order to establish whether a presumed 50% reduction in
      eEF1A2 expression was compatible with normal function. We evaluated the grip
      strength assay as a way of distinguishing between wasted and wild-type mice at 3
      4 weeks, and then performed the same assay in older +/wst and wild-type mice. We
      also used rotarod performance and immunohistochemistry of spinal cord sections to
      evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed
      no deficit in neuromuscular function or signs of spinal cord pathology, in spite
      of the low levels of eEF1A2.

PMID- 22848659
TI  - Dynamic expression of the translational machinery during Bacillus subtilis life
      cycle at a single cell level.
AB  - The ability of bacteria to responsively regulate the expression of translation
      components is crucial for rapid adaptation to fluctuating environments. Utilizing
      Bacillus subtilis (B. subtilis) as a model organism, we followed the dynamics of
      the translational machinery at a single cell resolution during growth and
      differentiation. By comprehensive monitoring the activity of the major rrn
      promoters and ribosomal protein production, we revealed diverse dynamics between
      cells grown in rich and poor medium, with the most prominent dissimilarities
      exhibited during deep stationary phase. Further, the variability pattern of
      translational activity varied among the cells, being affected by nutrient
      availability. We have monitored for the first time translational dynamics during
      the developmental process of sporulation within the two distinct cellular
      compartments of forespore and mother-cell. Our study uncovers a transient
      forespore specific increase in expression of translational components. Finally,
      the contribution of each rrn promoter throughout the bacterium life cycle was
      found to be relatively constant, implying that differential expression is not the
      main purpose for the existence of multiple rrn genes. Instead, we propose that
      coordination of the rrn operons serves as a strategy to rapidly fine tune
      translational activities in a synchronized fashion to achieve an optimal
      translation level for a given condition.

PMID- 22848660
TI  - Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three
      somatic mutations near the KCNJ5 potassium channel selectivity filter.
AB  - BACKGROUND: Aldosterone producing lesions are a common cause of hypertension, but
      genetic alterations for tumorigenesis have been unclear. Recently, either of two
      recurrent somatic missense mutations (G151R or L168R) was found in the potassium
      channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the
      channel selectivity filter and result in Na(+) conductance and cell
      depolarization, stimulating aldosterone production and cell proliferation.
      Because a similar mutation occurs in a mendelian form of primary aldosteronism,
      these mutations appear to be sufficient for cell proliferation and aldosterone
      production. The prevalence and spectrum of KCNJ5 mutations in different entities
      of adrenocortical lesions remain to be defined. MATERIALS AND METHODS: The coding
      region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA
      sequencing in 351 aldosterone producing lesions, from patients with primary
      aldosteronism and 130 other adrenocortical lesions. The specimens had been
      collected from 10 different worldwide referral centers. RESULTS: G151R or L168R
      somatic mutations were identified in 47% of aldosterone producing adenomas, each
      with similar frequency. A previously unreported somatic mutation near the
      selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations
      were also found in 40% of aldosterone producing adenomas associated with marked
      hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations
      were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were
      overrepresented in aldosterone producing adenomas from female compared to male
      patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than
      those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5
      mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005).
      DISCUSSION: Either of two somatic KCNJ5 mutations are highly prevalent and
      specific for aldosterone producing lesions. These findings provide new insight
      into the pathogenesis of primary aldosteronism.

PMID- 22848661
TI  - Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.
AB  - Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits
      varying combinations of sensorineural hearing loss and pigmentation defects. Four
      subtypes are clinically defined based on the presence or absence of additional
      symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10
      genes; however, 70% of WS2 cases remain unexplained at the molecular level,
      suggesting that other genes might be involved and/or that mutations within the
      known genes escaped previous screenings. The recent identification of a deletion
      encompassing three of the SOX10 regulatory elements in a patient presenting with
      another WS subtype, WS4, defined by its association with Hirschsprung disease,
      led us to search for deletions and point mutations within the MITF and SOX10
      regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations
      were identified: one in close proximity to the MITF distal enhancer (MDE) and one
      within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic
      effect of these variations, suggesting that mutations within regulatory elements
      of WS genes are not a major cause of this neurocristopathy.

PMID- 22848662
TI  - Polymorphisms on 8q24 are associated with lung cancer risk and survival in Han
      Chinese.
AB  - Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung
      cancer. Polymorphisms in this region are associated with risk of different
      cancers. To investigate the relationship between three single nucleotide
      polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung
      cancer risk, we conducted an association study in two Han Chinese populations:
      one population was from Zhejiang Province (576 case patients and 576 control
      subjects), whereas the other was from Fujian Province (576 case patients and 576
      control subjects). We found that rs6983267 was significantly associated with an
      increased risk of lung cancer in both populations. Compared with the TT genotype,
      the GG genotype was associated with a significant 1.555-fold increased risk of
      lung cancer [95% confidence interval (CI) 1.218-1.986, P = 4.0*10(-4)]. This
      effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI
      1.605-3.488, P = 1.4*10(-5)]. Analyses stratified by histology revealed that
      rs6983267 GG genotype was most associated with patients with other histological
      types (OR = 3.012, 95% CI 1.675-5.417, P = 2.3*10(-4)). The AA genotype of
      rs1447295 was associated with increased risk for adenocarcinoma compared with the
      CC genotype (OR = 2.260, 95% CI 1.174-4.353, P = 0.015). Furthermore, the GG
      genotype of rs6983267 was associated with worse survival in the Zhejiang
      population (hazard ratio (HR) = 1.646, 95% CI 1.099-2.464, P = 0.016). No
      association was observed for rs16901979. These results suggest that genetic
      variations on 8q24 may play significant roles in the development and progression
      of lung cancer.

PMID- 22848663
TI  - Hepatitis B virus X protein upregulates mTOR signaling through IKKbeta to
      increase cell proliferation and VEGF production in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), a major cause of cancer-related death in
      Southeast Asia, is frequently associated with hepatitis B virus (HBV) infection.
      HBV X protein (HBx), encoded by a viral non-structural gene, is a multifunctional
      regulator in HBV-associated tumor development. We investigated novel signaling
      pathways underlying HBx-induced liver tumorigenesis and found that the signaling
      pathway involving IkappaB kinase beta (IKKbeta), tuberous sclerosis complex 1
      (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase
      (S6K1), was upregulated when HBx was overexpressed in hepatoma cells. HBx-induced
      S6K1 activation was reversed by IKKbeta inhibitor Bay 11-7082 or silencing
      IKKbeta expression using siRNA. HBx upregulated cell proliferation and vascular
      endothelial growth factor (VEGF) production, and these HBx-upregulated phenotypes
      were abolished by treatment with IKKbeta inhibitor Bay 11-7082 or mTOR inhibitor
      rapamycin. The association of HBx-modulated IKKbeta/mTOR/S6K1 signaling with
      liver tumorigenesis was verified in a HBx transgenic mouse model in which
      pIKKbeta, pS6K1, and VEGF expression was found to be higher in cancerous than non
      cancerous liver tissues. Furthermore, we also found that pIKKbeta levels were
      strongly correlated with pTSC1 and pS6K1 levels in HBV-associated hepatoma tissue
      specimens taken from 95 patients, and that higher pIKKbeta, pTSC1, and pS6K1
      levels were correlated with a poor prognosis in these patients. Taken together,
      our findings demonstrate that HBx deregulates TSC1/mTOR signaling through
      IKKbeta, which is crucially linked to HBV-associated HCC development.

PMID- 22848664
TI  - Genome-wide transcriptional response of the archaeon Thermococcus gammatolerans
      to cadmium.
AB  - Thermococcus gammatolerans, the most radioresistant archaeon known to date, is an
      anaerobic and hyperthermophilic sulfur-reducing organism living in deep-sea
      hydrothermal vents. Knowledge of mechanisms underlying archaeal metal tolerance
      in such metal-rich ecosystem is still poorly documented. We showed that T.
      gammatolerans exhibits high resistance to cadmium (Cd), cobalt (Co) and zinc
      (Zn), a weaker tolerance to nickel (Ni), copper (Cu) and arsenate (AsO(4)) and
      that cells exposed to 1 mM Cd exhibit a cellular Cd concentration of 67 uM. A
      time-dependent transcriptomic analysis using microarrays was performed at a non
      toxic (100 uM) and a toxic (1 mM) Cd dose. The reliability of microarray data was
      strengthened by real time RT-PCR validations. Altogether, 114 Cd responsive genes
      were revealed and a substantial subset of genes is related to metal homeostasis,
      drug detoxification, re-oxidization of cofactors and ATP production. This first
      genome-wide expression profiling study of archaeal cells challenged with Cd
      showed that T. gammatolerans withstands induced stress through pathways observed
      in both prokaryotes and eukaryotes but also through new and original strategies.
      T. gammatolerans cells challenged with 1 mM Cd basically promote: 1) the
      induction of several transporter/permease encoding genes, probably to detoxify
      the cell; 2) the upregulation of Fe transporters encoding genes to likely
      compensate Cd damages in iron-containing proteins; 3) the induction of membrane
      bound hydrogenase (Mbh) and membrane-bound hydrogenlyase (Mhy2) subunits encoding
      genes involved in recycling reduced cofactors and/or in proton translocation for
      energy production. By contrast to other organisms, redox homeostasis genes appear
      constitutively expressed and only a few genes encoding DNA repair proteins are
      regulated. We compared the expression of 27 Cd responsive genes in other stress
      conditions (Zn, Ni, heat shock, gamma-rays), and showed that the Cd
      transcriptional pattern is comparable to other metal stress transcriptional
      responses (Cd, Zn, Ni) but not to a general stress response.

PMID- 22848665
TI  - Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6
      cys proteins: P12 and P41.
AB  - The genomes of Plasmodium parasites that cause malaria in humans, other primates,
      birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein
      family members reside on the surface at each extracellular life cycle stage and
      those on the surface of liver infective and sexual stages have been shown to play
      important roles in hepatocyte growth and fertilization respectively. However, 6
      cys proteins associated with the blood-stage forms of the parasite have no known
      function. Here we investigate the biochemical nature and function of two blood
      stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to
      afflict humans. We show that native P12 and P41 form a stable heterodimer on the
      infective merozoite surface and are secreted following invasion, but could find
      no evidence that this complex mediates erythrocyte-receptor binding. That P12 and
      P41 do not appear to have a major role as adhesins to erythrocyte receptors was
      supported by the observation that antisera to these proteins did not
      substantially inhibit erythrocyte invasion. To investigate other functional roles
      for these proteins their genes were successfully disrupted in P. falciparum,
      however P12 and P41 knockout parasites grew at normal rates in vitro and
      displayed no other obvious phenotypic changes. It now appears likely that these
      blood-stage 6-cys proteins operate as a pair and play redundant roles either in
      erythrocyte invasion or in host-immune interactions.

PMID- 22848666
TI  - Identification of the substrate recognition and transport pathway in a eukaryotic
      member of the nucleobase-ascorbate transporter (NAT) family.
AB  - Using the crystal structure of the uracil transporter UraA of Escherichia coli,
      we constructed a 3D model of the Aspergillus nidulans uric acid-xanthine/H(+)
      symporter UapA, which is a prototype member of the Nucleobase-Ascorbate
      Transporter (NAT) family. The model consists of 14 transmembrane segments (TMSs)
      divided into a core and a gate domain, the later being distinctly different from
      that of UraA. By implementing Molecular Mechanics (MM) simulations and
      quantitative structure-activity relationship (SAR) approaches, we propose a model
      for the xanthine-UapA complex where the substrate binding site is formed by the
      polar side chains of residues E356 (TMS8) and Q408 (TMS10) and the backbones of
      A407 (TMS10) and F155 (TMS3). In addition, our model shows several polar
      interactions between TMS1-TMS10, TMS1-TMS3, TMS8-TMS10, which seem critical for
      UapA transport activity. Using extensive docking calculations we identify a
      cytoplasm-facing substrate trajectory (D360, A363, G411, T416, R417, V463 and
      A469) connecting the proposed substrate binding site with the cytoplasm, as well
      as, a possible outward-facing gate leading towards the substrate major binding
      site. Most importantly, re-evaluation of the plethora of available and analysis
      of a number of herein constructed UapA mutations strongly supports the UapA
      structural model. Furthermore, modeling and docking approaches with mammalian NAT
      homologues provided a molecular rationale on how specificity in this family of
      carriers might be determined, and further support the importance of selectivity
      gates acting independently from the major central substrate binding site.

PMID- 22848667
TI  - IL-21 regulates the differentiation of a human gammadelta T cell subset equipped
      with B cell helper activity.
AB  - Vgamma9Vdelta2 T lymphocytes recognize nonpeptidic antigens without presentation
      by MHC molecules and display pleiotropic features. Here we report that coculture
      of Vgamma9Vdelta2 cells with phosphoantigen and IL-21 leads to selective
      expression of the transcription repressor Bcl-6 and polarization toward a
      lymphocyte subset displaying features of follicular B-helper T (T(FH)) cells.
      T(FH)-like Vgamma9Vdelta2 cells have a predominant central memory (CD27(+)CD45RA(
      )) phenotype and express ICOS, CD40L and CXCR5. Upon antigen activation, they
      secrete IL-4, IL-10 and CXCL13, and provide B-cell help for antibody production
      in vitro. Our findings delineate a subset of human Vgamma9Vdelta2 lymphocytes,
      which, upon interaction with IL-21-producing CD4 T(FH) cells and B cells in
      secondary lymphoid organs, is implicated in the production of high affinity
      antibodies against microbial pathogens.

PMID- 22848668
TI  - Tumor associated macrophage * cancer cell hybrids may acquire cancer stem cell
      properties in breast cancer.
AB  - Breast cancer is one of the most frequently diagnosed cancers among women, and
      metastasis makes it lethal. Tumor-associated macrophages (TAMs) that acquire an
      alternatively activated macrophage (M2) phenotype may promote metastasis.
      However, the underlying mechanisms are still elusive. Here, we examined how TAMs
      interact with breast cancer cells to promote metastasis. Immunohistochemistry was
      used to examine the expression of the M2-specific antigen CD163 in paraffin
      embedded mammary carcinoma blocks to explore fusion events in breast cancer
      patients. U937 cells were used as a substitute for human monocytes, and these
      cells differentiated into M2 macrophages following phorbol 12-myristate 13
      acetate (PMA) and M-CSF stimulation. M2 macrophages and the breast cancer cell
      lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol.
      Hybrids were isolated by fluorescence-activated cell sorting, and the relevant
      cell biological properties were compared with their parental counterparts. Breast
      cancer stem cell (BCSC)-related markers were quantified by immunofluorescence
      staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor
      initiating and metastatic capacities of the hybrids and their parental
      counterparts were assessed in NOD/SCID mice. We found that the CD163 expression
      rate in breast cancer tissues varied significantly and correlated with estrogen
      receptor status (p<0.05). The fusion efficiency of either breast cancer cell line
      with M2 macrophages ranged from 1.81 to 6.47% in the presence of PEG, and no
      significant difference was observed between the breast cancer cell lines used
      (p>0.05). Characterization of the fusion hybrids revealed a more aggressive
      phenotype, including increased migration, invasion and tumorigenicity, but
      reduced proliferative ability, compared with the parental lines. The hybrids also
      gained a CD44(+)CD24(-/low) phenotype and over-expressed epithelial-mesenchymal
      transition-associated genes. These results indicate that TAMs may promote breast
      cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

PMID- 22848669
TI  - Studies on the roles of clathrin-mediated membrane trafficking and zinc
      transporter Cis4 in the transport of GPI-anchored proteins in fission yeast.
AB  - We previously identified Cis4, a zinc transporter belonging to the cation
      diffusion facilitator protein family, and we demonstrated that Cis4 is implicated
      in Golgi membrane trafficking in fission yeast. Here, we identified three
      glycosylphosphatidylinositol (GPI)-anchored proteins, namely Ecm33, Aah3, and
      Gaz2, as multicopy suppressors of the MgCl(2)-sensitive phenotype of cis4-1
      mutant. The phenotypes of ecm33, aah3 and gaz2 deletion cells were distinct from
      each other, and Cis4 overexpression suppressed Deltaecm33 phenotypes but did not
      suppress Deltaaah3 defects. Notably, green fluorescent protein-tagged Ecm33,
      which was observed at the cell surface in wild-type cells, mostly localized as
      intracellular dots that are presumed to be the Golgi and endosomes in membrane
      trafficking mutants, including Deltaapm1, ypt3-i5, and chc1-1 mutants.
      Interestingly, all these membrane-trafficking mutants showed hypersensitivity to
      BE49385A, an inhibitor of Its8 that is involved in GPI-anchored protein
      synthesis. Taken together, these results suggest that GPI-anchored proteins are
      transported through a clathrin-mediated post-Golgi membrane trafficking pathway
      and that zinc transporter Cis4 may play roles in membrane trafficking of GPI
      anchored proteins in fission yeast.

PMID- 22848670
TI  - ATP hydrolyzing salivary enzymes of caterpillars suppress plant defenses.
AB  - The oral secretions of herbivores are important recognition cues that can be used
      by plants to mediate induced defenses. In this study, a degradation of adenosine
      5'-triphosphate (ATP) in tomato leaves was detected after treatment with
      Helicoverpa zea saliva. Correspondingly, a high level of ATPase activity in
      saliva was detected and three ATP hydrolyzing enzymes: apyrase, ATP synthase and
      ATPase 13A1 were identified in salivary glands. To determine the functions of
      these proteins in mediating defenses, they were cloned from H. zea and expressed
      in Escherichia coli. By applying the purified expressed apyrase, ATP synthase or
      ATPase 13A1 to wounded tomato leaves, it was determined that these ATP
      hydrolyzing enzymes suppressed the defensive genes regulated by the jasmonic acid
      and ethylene pathways in tomato plant. Suppression of glandular trichome
      production was also observed after treatment. Blood-feeding arthropods employ 5'
      nucleotidase family of apyrases to circumvent host responses and the H. zea
      apyrase, is also a member of this family. The comparatively high degree of
      sequence similarity of the H. zea salivary apyrase with mosquito apyrases
      suggests a broader evolutionary role for salivary apyrases than previously
      envisioned.

PMID- 22848671
TI  - Association of eleven common, low-penetrance colorectal cancer susceptibility
      genetic variants at six risk loci with clinical outcome.
AB  - BACKGROUND: Low-penetrance genetic variants have been increasingly recognized to
      influence the risk of tumor development. Risk variants for colorectal cancer
      (CRC) have been mapped to chromosome positions 8q23.3, 8q24, 9p24.1, 10p14,
      11q23, 14q22.2, 15q13, 16q22.1, 18q21, 19q13.1 and 20p12.3. In particular, the
      8q24 single nucleotide polymorphism (SNP), rs6983267, has reproducibly been
      associated with the risk of developing CRC. As the CRC risk SNPs may also
      influence disease outcome, thus in this study, we evaluated whether they
      influence patient survival. METHODOLOGY/PRINCIPAL FINDINGS: DNA samples from 583
      CRC patients enrolled in the prospective, North Carolina Cancer Care Outcomes
      Research and Surveillance Consortium Study (NC CanCORS) were genotyped for 11 CRC
      susceptibility SNPs at 6 CRC risk loci. Relationships between genotypes and
      patient survival were examined using Cox regression analysis. In multivariate
      analysis, patients homozygous for the CRC risk allele of rs7013278 or rs7014346
      (both at 8 q24) were only nominally significant for poorer overall survival
      compared to patients homozygous for the protective allele (hazard ratio = 2.20
      and 1.96, respectively; P<0.05). None of these associations, however, remained
      statistically significant after correction for multiple testing. The other nine
      susceptibility SNPs tested were not significantly associated with survival.
      CONCLUSIONS/SIGNIFICANCE: We did not find evidence of association of CRC risk
      variants with patient survival.

PMID- 22848673
TI  - Stimulus-entrained oscillatory activity propagates as waves from area 18 to 17 in
      cat visual cortex.
AB  - Previous studies in cat visual cortex reported that area 18 can actively drive
      neurons in area 17 through cortico-cortical projections. However, the dynamics of
      such cortico-cortical interaction remains unclear. Here we used multielectrode
      arrays to examine the spatiotemporal pattern of neuronal activity in cat visual
      cortex across the 17/18 border. We found that full-field contrast reversal
      gratings evoked oscillatory wave activity propagating from area 18 to 17. The
      wave direction was independent of the grating orientation, and could not be
      accounted for by the spatial distribution of receptive field latencies,
      suggesting that the waves are largely mediated by intrinsic connections in the
      cortex. Different from the evoked waves, spontaneous waves propagated along both
      directions across the 17/18 border. Together, our results suggest that visual
      stimulation may enhance the flow of information from area 18 to 17.

PMID- 22848672
TI  - A conserved non-reproductive GnRH system in chordates.
AB  - Gonadotropin-releasing hormone (GnRH) is a neuroendocrine peptide that plays a
      central role in the vertebrate hypothalamo-pituitary axis. The roles of GnRH in
      the control of vertebrate reproductive functions have been established, while its
      non-reproductive function has been suggested but less well understood. Here we
      show that the tunicate Ciona intestinalis has in its non-reproductive larval
      stage a prominent GnRH system spanning the entire length of the nervous system.
      Tunicate GnRH receptors are phylogenetically closest to vertebrate GnRH
      receptors, yet functional analysis of the receptors revealed that these simple
      chordates have evolved a unique GnRH system with multiple ligands and receptor
      heterodimerization enabling complex regulation. One of the gnrh genes is
      conspicuously expressed in the motor ganglion and nerve cord, which are
      homologous structures to the hindbrain and spinal cord of vertebrates.
      Correspondingly, GnRH receptor genes were found to be expressed in the tail
      muscle and notochord of embryos, both of which are phylotypic axial structures
      along the nerve cord. Our findings suggest a novel non-reproductive role of GnRH
      in tunicates. Furthermore, we present evidence that GnRH-producing cells are
      present in the hindbrain and spinal cord of the medaka, Oryzias latipes, thereby
      suggesting the deep evolutionary origin of a non-reproductive GnRH system in
      chordates.

PMID- 22848674
TI  - Comprehensive mutation analysis in colorectal flat adenomas.
AB  - BACKGROUND: Flat adenomas are a subgroup of colorectal adenomas that have been
      associated with a distinct biology and a more aggressive clinical behavior
      compared to their polypoid counterparts. In the present study, we aimed to
      compare the mutation spectrum of 14 cancer genes, between these two phenotypes.
      METHODS: A consecutive series of 106 flat and 93 polypoid adenomas was analyzed
      retrospectively for frequently occurring mutations in "hot spot" regions of KRAS,
      BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (beta-catenin),
      EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high
      throughput genotyping technique. Additionally, APC was analyzed using direct
      sequencing. RESULTS: APC mutations were more frequent in polypoid adenomas
      compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations
      in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both
      phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST
      G) no differences were observed for any of the investigated genes. CONCLUSION:
      The lower APC mutation rate in flat adenomas compared to polypoid adenomas
      suggests that disruption of the Wnt-pathway may occur via different mechanisms in
      these two phenotypes. Furthermore, in contrast to previous observations our
      results in this large well-defined sample set indicate that there is no
      significant association between the different morphological phenotypes and
      mutations in key genes of the RAS-RAF-MAPK pathway.

PMID- 22848675
TI  - Prospective validation of ELF test in comparison with Fibroscan and FibroTest to
      predict liver fibrosis in Asian subjects with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Liver stiffness measurement (LSM) and FibroTest (FT) are
      frequently used as non-invasive alternatives for fibrosis staging to liver
      biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis
      (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of
      procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have
      not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB)
      patients. METHODS: Between June 2010 and November 2011, we prospectively enrolled
      170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The
      Batts system was used to assess fibrosis stages. RESULTS: Areas under receiver
      operating characteristic curves (AUROCs) to predict significant fibrosis (F>=2),
      advanced fibrosis (F>=3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for
      ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881
      for FT. AUROCs to predict F>=2 were similar between each other, whereas LSM and
      FT had better AUROCs than ELF for predicting F>=3 (both p<0.05), and LSM
      predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to
      maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F>=2,
      F>=3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to
      diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients,
      respectively, were correctly classified according to histological results.
      CONCLUSIONS: ELF demonstrated considerable diagnostic value in fibrosis staging
      in Asian CHB patients, especially in predicting F>=2. However, LSM consistently
      provided better performance for predicting F>=3 and F4.

PMID- 22848676
TI  - DNase SISPA-next generation sequencing confirms Schmallenberg virus in Belgian
      field samples and identifies genetic variation in Europe.
AB  - In 2011, a novel Orthobunyavirus was identified in cattle and sheep in Germany
      and The Netherlands. This virus was named Schmallenberg virus (SBV). Later,
      presence of the virus was confirmed using real time RT-PCR in cases of congenital
      malformations of bovines and ovines in several European countries, including
      Belgium. In the absence of specific sequencing protocols for this novel virus we
      confirmed its presence in RT-qPCR positive field samples using DNase SISPA-next
      generation sequencing (NGS), a virus discovery method based on random
      amplification and next generation sequencing. An in vitro transcribed RNA was
      used to construct a standard curve allowing the quantification of viral RNA in
      the field samples. Two field samples of aborted lambs containing 7.66 and 7.64
      log(10) RNA copies per uL total RNA allowed unambiguous identification of SBV.
      One sample yielded 192 SBV reads covering about 81% of the L segment, 56% of the
      M segment and 13% of the S segment. The other sample resulted in 8 reads
      distributed over the L and M segments. Three weak positive field samples (one
      from an aborted calf, two from aborted lambs) containing virus quantities
      equivalent to 4.27-4.89 log(10) RNA copies per uL did not allow identification
      using DNase SISPA-NGS. This partial sequence information was compared to the
      whole genome sequence of SBV isolated from bovines in Germany, identifying
      several sequence differences. The applied viral discovery method allowed the
      confirmation of SBV in RT-qPCR positive brain samples. However, the failure to
      confirm SBV in weak PCR-positive samples illustrates the importance of the
      selection of properly targeted and fresh field samples in any virus discovery
      method. The partial sequences derived from the field samples showed several
      differences compared to the sequences from bovines in Germany, indicating
      sequence divergence within the epidemic.

PMID- 22848678
TI  - HILI inhibits TGF-beta signaling by interacting with Hsp90 and promoting TbetaR
      degradation.
AB  - PIWIL2, called HILI in humans, is a member of the PIWI subfamily. This subfamily
      has highly conserved PAZ and Piwi domains and is implicated in several critical
      functions, including embryonic development, stem-cell self-renewal, RNA
      silencing, and translational control. However, the underlying molecular mechanism
      remains largely unknown. Transforming growth factor-beta (TGF-beta) is a secreted
      multifunctional protein that controls several developmental processes and the
      pathogenesis of many diseases. TGF-beta signaling is activated by phosphorylation
      of transmembrane serine/threonine kinase receptors, TGF-beta type II (TbetaRII),
      and type I (TbetaRI), which are stabilized by Hsp90 via specific interactions
      with this molecular chaperone. Here, we present evidence that HILI suppresses TGF
      beta signaling by physically associating with Hsp90 in human embryonic kidney
      cells (HEK-293). Our research shows that HILI mediates the loss of TGF-beta
      induced Smad2/3 phosphorylation. We also demonstrate that HILI interacts with
      Hsp90 to prevent formation of Hsp90-TbetaR heteromeric complexes, and improves
      ubiquitination and degradation of TbetaRs dependent on the ubiquitin E3 ligase
      Smurf2. This work reveals a critical negative regulation level of TGF-beta
      signaling mediated by HILI (human PIWIL2) by its ability to interact with Hsp90
      and promote TbetaR degradation.

PMID- 22848677
TI  - Complement receptors 1 and 2 in murine antibody responses to IgM-complexed and
      uncomplexed sheep erythrocytes.
AB  - Early complement components are important for normal antibody responses. In this
      process, complement receptors 1 and 2 (CR1/2), expressed on B cells and
      follicular dendritic cells (FDCs) in mice, play a central role. Complement
      activating IgM administered with the antigen it is specific for, enhances the
      antibody response to this antigen. Here, bone marrow chimeras between Cr2(-/-)
      and wildtype mice were used to analyze whether FDCs or B cells must express CR1/2
      for antibody responses to sheep erythrocytes (SRBC), either administered alone or
      together with specific IgM. For robust IgG anti-SRBC responses, CR1/2 must be
      expressed on FDCs. Occasionally, weak antibody responses were seen when only B
      cells expressed CR1/2, probably reflecting extrafollicular antibody production
      enabled by co-crosslinking of CR2/CD19/CD81 and the BCR. When SRBC alone was
      administered to mice with CR1/2(+) FDCs, B cells from wildtype and Cr2(-/-) mice
      produced equal amounts of antibodies. Most likely antigen is then deposited on
      FDCs in a way that optimizes engagement of the B cell receptor, making CR2
      facilitated signaling to the B cell superfluous. SRBC bound to IgM will have more
      C3 fragments, the ligands for CR1/2, on their surface than SRBC administered
      alone. Specific IgM, forming a complex with SRBC, enhances antibody responses in
      two ways when FDCs express CR1/2. One is dependent on CR1/2(+) B cells and
      probably acts via increased transport of IgM-SRBC-complement complexes bound to
      CR1/2 on marginal zone B cells. The other is independent on CR1/2(+) B cells and
      the likely mechanism is that IgM-SRBC-complement complexes bind better to FDCs
      than SRBC administered alone. These observations suggest that the immune system
      uses three different CR1/2-mediated effector functions to generate optimal
      antibody responses: capture by FDCs (playing a dominant role), transport by
      marginal zone B cells and enhanced B cell signaling.

PMID- 22848679
TI  - NMR structure of Hsp12, a protein induced by and required for dietary restriction
      induced lifespan extension in yeast.
AB  - Dietary restriction (DR) extends lifespan in yeast, worms, flies and mammals,
      suggesting that it may act via conserved processes. However, the downstream
      mechanisms by which DR increases lifespan remain unclear. We used a gel based
      proteomic strategy to identify proteins whose expression was induced by DR in
      yeast and thus may correlate with longevity. One protein up-regulated by DR was
      Hsp12, a small heat shock protein induced by various manipulations known to
      retard ageing. Lifespan extension by growth on 0.5% glucose (DR) was abolished in
      an hsp12Delta strain, indicating that Hsp12 is essential for the longevity effect
      of DR. In contrast, deletion of HSP12 had no effect on growth under DR conditions
      or a variety of environmental stresses, indicating that the effect of Hsp12 on
      lifespan is not due to increased general stress resistance. Unlike other small
      heat shock proteins, recombinant Hsp12 displayed negligible in vitro molecular
      chaperone activity, suggesting that its cellular function does not involve
      preventing protein aggregation. NMR analysis indicated that Hsp12 is monomeric
      and intrinsically unfolded in solution, but switches to a 4-helical conformation
      upon binding to membrane-mimetic SDS micelles. The structure of micelle-bound
      Hsp12 reported here is consistent with its recently proposed function as a
      membrane-stabilising 'lipid chaperone'. Taken together, our data suggest that DR
      induced Hsp12 expression contributes to lifespan extension, possibly via membrane
      alterations.

PMID- 22848680
TI  - Shared human-chimpanzee pattern of perinatal femoral shaft morphology and its
      implications for the evolution of hominin locomotor adaptations.
AB  - BACKGROUND: Acquisition of bipedality is a hallmark of human evolution. How
      bipedality evolved from great ape-like locomotor behaviors, however, is still
      highly debated. This is mainly because it is difficult to infer locomotor
      function, and even more so locomotor kinematics, from fossil hominin long bones.
      Structure-function relationships are complex, as long bone morphology reflects
      phyletic history, developmental programs, and loading history during an
      individual's lifetime. Here we discriminate between these factors by
      investigating the morphology of long bones in fetal and neonate great apes and
      humans, before the onset of locomotion. METHODOLOGY/PRINCIPAL FINDINGS:
      Comparative morphometric analysis of the femoral diaphysis indicates that its
      morphology reflects phyletic relationships between hominoid taxa to a greater
      extent than taxon-specific locomotor adaptations. Diaphyseal morphology in humans
      and chimpanzees exhibits several shared-derived features, despite substantial
      differences in locomotor adaptations. Orangutan and gorilla morphologies are
      largely similar, and likely represent the primitive hominoid state.
      CONCLUSIONS/SIGNIFICANCE: These findings are compatible with two possible
      evolutionary scenarios. Diaphyseal morphology may reflect retained adaptive
      traits of ancestral taxa, hence human-chimpanzee shared-derived features may be
      indicative of the locomotor behavior of our last common ancestor. Alternatively,
      diaphyseal morphology might reflect evolution by genetic drift (neutral
      evolution) rather than selection, and might thus be more informative about
      phyletic relationships between taxa than about locomotor adaptations. Both
      scenarios are consistent with the hypothesis that knuckle-walking in chimpanzees
      and gorillas resulted from convergent evolution, and that the evolution of human
      bipedality is unrelated to extant great ape locomotor specializations.

PMID- 22848681
TI  - Association of polymorphism in pri-microRNAs-371-372-373 with the occurrence of
      hepatocellular carcinoma in hepatitis B virus infected patients.
AB  - BACKGROUND: Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same
      pri-miRNA transcript, are reported to be upregulated in hepatocellular carcinoma
      (HCC) and to be related to the regulation of hepatitis B virus (HBV) infection.
      Our study investigated whether pri-miRNAs-371-373 polymorphisms are associated
      with the risk of HCC occurrence and HBV clearance. METHODS: Genetic variations
      were identified through direct DNA sequencing using TaqMan assay. Three sequence
      variants of pri-miRNAs-371-373 were identified. Genetic associations of those
      with HCC occurrence and HBV clearance among patients with HBV infection were
      analyzed using logistic regression analyses with adjustment for age and gender (n
      = 1439). RESULTS: For the occurrence of HCC, polymorphism rs3859501C>A acted as a
      protective factor both in chronic carriers (OR = 0.75, P = 0.005 in a codominant
      model; OR = 0.71, P = 0.02 in a dominant model; OR = 0.66, P = 0.03 in recessive
      model) and liver cirrhosis patients (OR = 0.69, P = 0.001 in a codominant model;
      OR = 0.60, P = 0.003 in a dominant model; OR = 0.63, P = 0.03 in a recessive
      model). The pri-miRNAs-371-373_ht2 [C-A-C] also showed a protective effect on HCC
      occurrence both in the chronic carrier and liver cirrhosis groups (P<0.05 in
      both). However, there was no significant association between pri-miRNAs-371-373
      polymorphisms and HBV clearance. CONCLUSIONS: In conclusion, among chronic
      carriers and liver cirrhosis patients, the A allele of rs3859501 and the
      haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes
      and haplotypes. Further studies into the roles of rs3859501 and pri-miRNAs-371
      373_ht2 haplotype in hepatocarcinogenesis are needed.

PMID- 22848682
TI  - Acyl chains of phospholipase D transphosphatidylation products in Arabidopsis
      cells: a study using multiple reaction monitoring mass spectrometry.
AB  - BACKGROUND: Phospholipases D (PLD) are major components of signalling pathways in
      plant responses to some stresses and hormones. The product of PLD activity is
      phosphatidic acid (PA). PAs with different acyl chains do not have the same
      protein targets, so to understand the signalling role of PLD it is essential to
      analyze the composition of its PA products in the presence and absence of an
      elicitor. METHODOLOGY/PRINCIPAL FINDINGS: Potential PLD substrates and products
      were studied in Arabidopsis thaliana suspension cells treated with or without the
      hormone salicylic acid (SA). As PA can be produced by enzymes other than PLD, we
      analyzed phosphatidylbutanol (PBut), which is specifically produced by PLD in the
      presence of n-butanol. The acyl chain compositions of PBut and the major
      glycerophospholipids were determined by multiple reaction monitoring (MRM) mass
      spectrometry. PBut profiles of untreated cells or cells treated with SA show an
      over-representation of 160/18:2- and 16:0/18:3-species compared to those of
      phosphatidylcholine and phosphatidylethanolamine either from bulk lipid extracts
      or from purified membrane fractions. When microsomal PLDs were used in in vitro
      assays, the resulting PBut profile matched exactly that of the substrate
      provided. Therefore there is a mismatch between the acyl chain compositions of
      putative substrates and the in vivo products of PLDs that is unlikely to reflect
      any selectivity of PLDs for the acyl chains of substrates. CONCLUSIONS: MRM mass
      spectrometry is a reliable technique to analyze PLD products. Our results suggest
      that PLD action in response to SA is not due to the production of a stress
      specific molecular species, but that the level of PLD products per se is
      important. The over-representation of 160/18:2- and 16:0/18:3-species in PLD
      products when compared to putative substrates might be related to a regulatory
      role of the heterogeneous distribution of glycerophospholipids in membrane sub
      domains.

PMID- 22848683
TI  - Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased
      activation by glargine but not by its metabolites M1 and M2.
AB  - BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin
      does not permit optimal control of glycemia. Fast and slow acting insulin
      analogues have been developed, but they may have adverse properties, such as
      increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors
      (IR/IGF1R), present in most tissues, have been proposed to transmit biological
      effects close to those of IGF1R. However, the study of hybrid receptors is
      difficult because of the presence of IR and IGF1R homodimers. Our objective was
      to perform the first study on the pharmacological properties of the five marketed
      insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of
      insulin analogues on IR/IGF1R hybrids, we used our previously developed
      Bioluminescence Resonance Energy Transfer (BRET) assay that permits specific
      analysis of the pharmacological properties of hybrid receptors. Moreover, we have
      developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol
      3 phosphate (PIP(3)) production in living cells. Using this assay, we performed a
      detailed pharmacological analysis of PIP(3) production induced by IGF1, insulin
      and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells.
      RESULTS: Among the five insulin analogues tested, only glargine stimulated
      IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close
      to that of IGF1. Glargine more efficiently stimulated PIP(3) production in MCF-7
      cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine
      metabolites M1 and M2 showed lower potency for hybrid receptors stimulation,
      PIP(3) production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7
      cells, compared to insulin. CONCLUSION: Glargine, possibly acting through
      IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2
      display lower potency than insulin for the stimulation of proliferative/anti
      apoptotic pathways in MCF-7 cells.

PMID- 22848685
TI  - The halo effect: suppression of pink bollworm on non-Bt cotton by Bt cotton in
      China.
AB  - In some previously reported cases, transgenic crops producing insecticidal
      proteins from Bacillus thuringiensis (Bt) have suppressed insect pests not only
      in fields planted with such crops, but also regionally on host plants that do not
      produce Bt toxins. Here we used 16 years of field data to determine if Bt cotton
      caused this "halo effect" against pink bollworm (Pectinophora gossypiella) in six
      provinces of the Yangtze River Valley of China. In this region, the percentage of
      cotton hectares planted with Bt cotton increased from 9% in 2000 to 94% in 2009
      and 2010. We found that Bt cotton significantly decreased the population density
      of pink bollworm on non-Bt cotton, with net decreases of 91% for eggs and 95% for
      larvae on non-Bt cotton after 11 years of Bt cotton use. Insecticide sprays
      targeting pink bollworm and cotton bollworm (Helicoverpa armigera) decreased by
      69%. Previously reported evidence of the early stages of evolution of pink
      bollworm resistance to Bt cotton in China has raised concerns that if unchecked,
      such resistance could eventually diminish or eliminate the benefits of Bt cotton.
      The results reported here suggest that it might be possible to find a percentage
      of Bt cotton lower than the current level that causes sufficient regional pest
      suppression and reduces the risk of resistance.

PMID- 22848684
TI  - Identification of a novel small RNA modulating Francisella tularensis
      pathogenicity.
AB  - Francisella tularensis is a highly virulent bacterium responsible for the
      zoonotic disease tularemia. It is a facultative intracellular pathogen that
      replicates in the cytoplasm of host cells, particularly in macrophages. Here we
      show that F. tularensis live vaccine strain (LVS) expresses a novel small RNA
      (sRNA), which modulates the virulence capacities of the bacterium. When this
      sRNA, designated FtrC (for Francisella tularensis RNA C), is expressed at high
      levels, F. tularensis replicates in macrophages less efficiently than the wild
      type parent strain. Similarly, high expression of FtrC reduces the number of
      viable bacteria recovered from the spleen and liver of infected mice. Our data
      demonstrate that expression of gene FTL_1293 is regulated by FtrC. Furthermore,
      we show by in vitro gel shift assays that FtrC interacts specifically with
      FTL_1293 mRNA and that this happens independently of the RNA chaperone Hfq.
      Remarkably, FtrC interacts only with full-length FTL_1293 mRNA. These results,
      combined with a bioinformatic analysis, indicate that FtrC interacts with the
      central region of the mRNA and hence does not act by sterically hindering access
      of the ribosome to the mRNA. We further show that gene FTL_1293 is not required
      for F. tularensis virulence in vitro or in vivo, which indicates that another
      unidentified FtrC target modulates the virulence capacity of the bacterium.

PMID- 22848686
TI  - The odyssey of Hsp60 from tumor cells to other destinations includes plasma
      membrane-associated stages and Golgi and exosomal protein-trafficking modalities.
AB  - BACKGROUND: In a previous work we showed for the first time that human tumor
      cells secrete Hsp60 via exosomes, which are considered immunologically active
      microvesicles involved in tumor progression. This finding raised questions
      concerning the route followed by Hsp60 to reach the exosomes, its location in
      them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the
      Golgi. We addressed these issues in the work presented here. PRINCIPAL FINDINGS:
      We found that Hsp60 localizes in the tumor cell plasma membrane, is associated
      with lipid rafts, and ends up in the exosomal membrane. We also found evidence
      that Hsp60 localizes in the Golgi apparatus and its secretion is prevented by an
      inhibitor of this organelle. CONCLUSIONS/SIGNIFICANCE: We propose a multistage
      process for the translocation of Hsp60 from the inside to the outside of the cell
      that includes a combination of protein traffic pathways and, ultimately, presence
      of the chaperonin in the circulating blood. The new information presented should
      help in designing future strategies for research and for developing diagnostic
      monitoring means useful in clinical oncology.

PMID- 22848687
TI  - Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure
      and hypertension in Chinese population.
AB  - Dysregulation of the complement system has been linked to pathogenesis of
      hypertension. However, whether genetic changes of complement factor H (CFH) and
      its related genes are associated with hypertension is unknown. We genotyped three
      SNPs in the CFH gene cluster that are closely linked to age-related macular
      degeneration, namely rs1061170 (Y402H), rs2274700 (A473A) and rs7542235 (CFHR1
      3Delta), and tested for their associations with blood pressure and hypertension
      risk in a population-based cohort including 3,210 unrelated Chinese Hans (50-70
      years of age) from Beijing and Shanghai. We found that rs2274700 (A473A) and
      rs7542235 (CFHR1-3Delta) were both significantly associated with diastolic blood
      pressure (DBP) (beta = 0.632-1.431, P<=0.038) and systolic blood pressure (SBP)
      (beta = 1.567-4.445, P<=0.008), and rs2274700 (A473A) was associated with
      hypertension risk (OR [95%CI]: 1.175 [1.005-1.373], P = 0.048). Notably, the
      associations of rs2274700 (A473A) with DBP (P = 2.1*10(-3)), SBP (P = 8*10(-5))
      and hypertension risk (P = 7.9*10(-3)) were significant only in the individuals
      with low CRP levels (<2.0 mg/l), but not in those with CRP levels >=2.0 mg/l
      (P>=0.0807) (P for interaction <=0.0467). However, no significant association
      between rs1061170 (Y402H) and blood pressure or hypertension risk was observed
      (P>=0.259). In conclusion, our results suggest that genetic variations in CFH and
      its related genes may contribute to hypertension risk in Chinese Hans.

PMID- 22848688
TI  - Dysregulation of Th17 cells during the early post-transplant period in patients
      under calcineurin inhibitor based immunosuppression.
AB  - Accumulating evidence suggests that Th17 cells play a role in the development of
      chronic allograft injury in transplantation of various organs. However, the
      influence of current immunosuppressants on Th17-associated immune responses has
      not been fully investigated. We prospectively investigated the changes in Th17
      cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3
      months after KT in 26 patients and we investigated the suppressive effect of
      tacrolimus on Th17 in vitro. In the early posttransplant period, the percentage
      of Th17 cells and the proportion of IL-17-producing cells in the effector memory
      T cells (TEM) were significantly increased at 3 months after transplantation
      compared with before transplantation (P<0.05), whereas Th1/Th2 cells and TEM
      cells were significantly decreased. The degree of increase in Th17 during the
      early posttransplant period was significantly associated with allograft function
      at 1 year after transplantation (r = 0.4, P<0.05). In vitro, tacrolimus
      suppressed Th1 and Th2 cells in a concentration-dependent manner, but did not
      suppress Th17 cells even at high concentration. This suggests that current
      immunosuppression based on tacrolimus is inadequate to suppress Th17 cells in
      KTRs, and dysregulation of Th17 may be associated with the progression of CAD.

PMID- 22848689
TI  - PAK1 kinase promotes cell motility and invasiveness through CRK-II serine
      phosphorylation in non-small cell lung cancer cells.
AB  - The role of c-Crk (CRK) in promoting metastasis is well described however the
      role of CRK phosphorylation and the corresponding signaling events are not well
      explained. We have observed CRK-II serine 41 phosphorylation is inversely
      correlated with p120-catenin and E-cadherin expressions in non-small cell lung
      cancer (NSCLC) cells. Therefore, we investigated the role of CRK-II serine 41
      phosphorylation in the down-regulation of p120-catenin, cell motility and cell
      invasiveness in NSCLC cells. For this purpose, we expressed phosphomimetic and
      phosphodeficient CRK-II serine 41 mutants in NSCLC cells. NSCLC cells expressing
      phosphomimetic CRK-II seine 41 mutant showed lower p120-catenin level while CRK
      II seine 41 phosphodeficient mutant expression resulted in higher p120-catenin.
      In addition, A549 cells expressing CRK-II serine 41 phosphomimetic mutant
      demonstrated more aggressive behavior in wound healing and invasion assays and,
      on the contrary, expression of phosphodeficient CRK-II serine 41 mutant in A549
      cells resulted in reduced cell motility and invasiveness. We also provide
      evidence that PAK1 mediates CRK-II serine 41 phosphorylation. RNAi mediated
      silencing of PAK1 increased p120-catenin level in A549 and H157 cells.
      Furthermore, PAK1 silencing decreased cell motility and invasiveness in A549
      cells. These effects were abrogated in A549 cells expressing phosphomimetic CRK
      II serine 41. In summary, these data provide evidence for the role of PAK1 in the
      promotion of cell motility, cell invasiveness and the down regulation of p120
      catenin through CRK serine 41 phosphorylation in NSCLC cells.

PMID- 22848691
TI  - Which is a more accurate predictor in colorectal survival analysis? Nine data
      mining algorithms vs. the TNM staging system.
AB  - OBJECTIVE: Over the past decades, many studies have used data mining technology
      to predict the 5-year survival rate of colorectal cancer, but there have been few
      reports that compared multiple data mining algorithms to the TNM classification
      of malignant tumors (TNM) staging system using a dataset in which the training
      and testing data were from different sources. Here we compared nine data mining
      algorithms to the TNM staging system for colorectal survival analysis. METHODS:
      Two different datasets were used: 1) the National Cancer Institute's
      Surveillance, Epidemiology, and End Results dataset; and 2) the dataset from a
      single Chinese institution. An optimization and prediction system based on nine
      data mining algorithms as well as two variable selection methods was implemented.
      The TNM staging system was based on the 7(th) edition of the American Joint
      Committee on Cancer TNM staging system. RESULTS: When the training and testing
      data were from the same sources, all algorithms had slight advantages over the
      TNM staging system in predictive accuracy. When the data were from different
      sources, only four algorithms (logistic regression, general regression neural
      network, bayesian networks, and Naive Bayes) had slight advantages over the TNM
      staging system. Also, there was no significant differences among all the
      algorithms (p>0.05). CONCLUSIONS: The TNM staging system is simple and practical
      at present, and data mining methods are not accurate enough to replace the TNM
      staging system for colorectal cancer survival prediction. Furthermore, there were
      no significant differences in the predictive accuracy of all the algorithms when
      the data were from different sources. Building a larger dataset that includes
      more variables may be important for furthering predictive accuracy.

PMID- 22848690
TI  - Impact of loading phase, initial response and CFH genotype on the long-term
      outcome of treatment for neovascular age-related macular degeneration.
AB  - OBJECTIVE: Factors influencing the outcome of anti-VEGF treatment in neovascular
      AMD are still investigated. We analyzed the impact of a loading phase, the
      significance of an initial response for the long-term and the effect of the CFH
      polymorphism (p.His402Tyr) on treatment outcome. METHODS: Patients treated with
      ranibizumab for neovascular AMD were analyzed over a period of 24 months by
      assessing effects of loading phase, initial response and genotype of CFH
      rs1061170 (c.1204C>T, p.His402Tyr). RESULTS: 204 eyes were included. A change of
      +5.0 [-1;+11] letters and +1.5 [-5.5;+9.5] was observed with a median of 4 [3];
      [7] and 10 [7]; [14] ranibizumab injections during 12 and 24 months,
      respectively. Loading phase was no significant predictor for treatment as VA
      outcome in eyes with and without loading phase was similar (p = 0.846 and p =
      0.729) at 12 and 24 months. In contrast, initial response was a significant
      predictor for improving vision of 5 or more letters at 12 (p = 0.001; OR = 6.75)
      and 24 months (p = 0.01; OR = 4.66). Furthermore, the CT genotype at CFH
      rs1061170 was identified as a significant predictor for a favorable VA outcome at
      12 and 24 months (OR = 6.75, p = 0.001 and OR = 4.66, p = 0.01). CONCLUSIONS: Our
      data suggest that clinical decisions regarding treatment may be guided by
      observing patients' initial response as well as their genotype of SNP rs1061170,
      while the criterion of loading phase may not bear the customary value.

PMID- 22848692
TI  - Altered regional homogeneity in the development of minimal hepatic
      encephalopathy: a resting-state functional MRI study.
AB  - BACKGROUND: Little is known about how spontaneous brain activity progresses from
      non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this
      study was to evaluate the evolution pattern of spontaneous brain activities in
      cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo)
      method. METHODOLOGY/PRINCIPAL FINDINGS: Resting-state fMRI data were acquired in
      47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age
      and sex-matched healthy controls. The Kendall's coefficient of concordance (KCC)
      was used to measure the regional homogeneity. The regional homogeneity maps were
      compared with ANOVA tests among MHE, non-HE, and healthy control groups and t
      tests between each pair in a voxel-wise way. Correlation analyses were performed
      to explore the relationships between regional ReHo values and Child-Pugh scores,
      number connection test type A (NCT-A), digit symbol test (DST) scores, venous
      blood ammonia levels. Compared with healthy controls, both MHE and non-HE
      patients showed decreased ReHo in the bilateral frontal, parietal and temporal
      lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE
      patients showed decreased ReHo in the bilateral precuneus, cuneus and
      supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively
      correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST
      scores positively correlated with ReHo values in the cuneus, precuneus and
      lingual gyrus, and negatively correlated with ReHo values in the bilateral
      caudate (P<0.05, AlphaSim corrected). CONCLUSIONS/SIGNIFICANCE: Diffused abnormal
      homogeneity of baseline brain activity was nonspecific for MHE, and only the
      progressively decreased ReHo in the SMA and the cuneus, especially for the
      latter, might be associated with the development of MHE. The ReHo analysis may be
      potentially valuable for detecting the development from non-HE to MHE.

PMID- 22848693
TI  - Algivore or phototroph? Plakobranchus ocellatus (Gastropoda) continuously
      acquires kleptoplasts and nutrition from multiple algal species in nature.
AB  - The sea slug Plakobranchus ocellatus (Sacoglossa, Gastropoda) retains
      photosynthetically active chloroplasts from ingested algae (functional
      kleptoplasts) in the epithelial cells of its digestive gland for up to 10 months.
      While its feeding behavior has not been observed in natural habitats, two
      hypotheses have been proposed: 1) adult P. ocellatus uses kleptoplasts to obtain
      photosynthates and nutritionally behaves as a photoautotroph without replenishing
      the kleptoplasts; or 2) it behaves as a mixotroph (photoautotroph and herbivorous
      consumer) and replenishes kleptoplasts continually or periodically. To address
      the question of which hypothesis is more likely, we examined the source algae for
      kleptoplasts and temporal changes in kleptoplast composition and nutritional
      contribution. By characterizing the temporal diversity of P. ocellatus
      kleptoplasts using rbcL sequences, we found that P. ocellatus harvests
      kleptoplasts from at least 8 different siphonous green algal species, that
      kleptoplasts from more than one species are present in each individual sea slug,
      and that the kleptoplast composition differs temporally. These results suggest
      that wild P. ocellatus often feed on multiple species of siphonous algae from
      which they continually obtain fresh chloroplasts. By estimating the trophic
      position of wild and starved P. ocellatus using the stable nitrogen isotopic
      composition of amino acids, we showed that despite the abundance of kleptoplasts,
      their photosynthates do not contribute greatly to the nutrition of wild P.
      ocellatus, but that kleptoplast photosynthates form a significant source of
      nutrition for starved sea slugs. The herbivorous nature of wild P. ocellatus is
      consistent with insights from molecular analyses indicating that kleptoplasts are
      frequently replenished from ingested algae, leading to the conclusion that
      natural populations of P. ocellatus do not rely on photosynthesis but mainly on
      the digestion of ingested algae.

PMID- 22848694
TI  - Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion
      injury.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (I/R) plays an important role in
      critical illnesses. Gut flora participate in the pathogenesis of the injury. This
      study is aimed at unraveling colonic microbiota alteration pattern and
      identifying specific bacterial species that differ significantly as well as
      observing colonic epithelium change in the same injury model during the
      reperfusion time course. METHODOLOGY/PRINCIPAL FINDINGS: Denaturing gradient gel
      electrophoresis (DGGE) was used to monitor the colonic microbiota of control rats
      and experimental rats that underwent 0.5 hour ischemia and 1, 3, 6, 12, 24, and
      72 hours following reperfusion respectively. The microbiota similarity, bacterial
      diversity and species that characterized the dysbiosis were estimated based on
      the DGGE profiles using a combination of statistical approaches. The interested
      bacterial species in the gel were cut and sequenced and were subsequently
      quantified and confirmed with real-time PCR. Meanwhile, the epithelial barrier
      was checked by microscopy and D-lactate analysis. Colonic flora changed early and
      differed significantly at 6 hours after reperfusion and then started to recover.
      The shifts were characterized by the increase of Escherichia coli and Prevotella
      oralis, and Lactobacilli proliferation together with epithelia healing.
      CONCLUSION/SIGNIFICANCE: This study shows for the first time that intestinal
      ischemia-reperfusion results in colonic flora dysbiosis that follows epithelia
      damage, and identifies the bacterial species that contribute most.

PMID- 22848695
TI  - The Mph1 helicase can promote telomere uncapping and premature senescence in
      budding yeast.
AB  - Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining
      (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are
      refractory to repair events in order to prevent chromosome end fusions and
      genomic instability. In some rare instances telomeres engage in Break-Induced
      Replication (BIR), a type of HR, in order to maintain telomere length in the
      absence of the enzyme telomerase. Here we have investigated how the yeast
      helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that
      overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to
      proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits
      NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At
      telomeres Mph1 is able to promote telomere uncapping and the accumulation of
      ssDNA, which results in premature senescence in the absence of telomerase. We
      propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ)
      at telomeres by remodeling them into a nuclease-sensitive structure, which
      promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put
      forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but
      promotes senescence in cells with dysfunctional telomeres by increasing the
      levels of ssDNA.

PMID- 22848696
TI  - Stavudine toxicity in adult longer-term ART patients in Blantyre, Malawi.
AB  - BACKGROUND: Stavudine is an effective and inexpensive antiretroviral drug, but no
      longer recommended by WHO for first-line antiretroviral regimens in resource
      limited settings due to toxicity concerns. Because of the high cost of
      alternative drugs, it has not been feasible to replace stavudine in most adults
      in the Malawi ART programme. We aimed to provide policy makers with a detailed
      picture of stavudine toxicities in Malawians on longer-term ART, in order to
      facilitate prioritization of stavudine replacement among other measures to
      improve the quality of ART programmes. METHODS: Prospective cohort of Malawian
      adults who had just completed one year of stavudine containing ART in an urban
      clinic, studying peripheral neuropathy, lipodystrophy, diabetes mellitus, high
      lactate syndromes, pancreatitis and dyslipidemia during 12 months follow up.
      Stavudine dosage was 30 mg irrespective of weight. Cox regression was used to
      determine associations with incident toxicities. RESULTS: 253 patients were
      enrolled, median age 36 years, 62.5% females. Prevalence rates (95%-confidence
      interval) of toxicities after one year on stavudine were: peripheral neuropathy
      21.3% (16.5-26.9), lipodystrophy 14.7% (2.4-8.1), high lactate syndromes 0.0% (0
      1.4), diabetes mellitus 0.8% (0-2.8), pancreatitis 0.0% (0-1.5). Incidence rates
      per 100 person-years (95%-confidence interval) during the second year on
      stavudine were: peripheral neuropathy 19.8 (14.3-26.6), lipodystrophy 11.4 (7.5
      16.3), high lactate syndromes 2.1 (0.7-4.9), diabetes mellitus 0.4 (0.0-1.4),
      pancreatitis 0.0 (0.0-0.2). Prevalence of hypercholesterolemia and
      hypertriglyceridemia increased from 12.1% to 21.1% and from 29.5% to 37.6%
      respectively between 12 and 24 months. 5.5% stopped stavudine, 1.3% died and 4.0%
      defaulted during follow up. Higher age was an independent risk factor for
      incident peripheral neuropathy and lipodystrophy. CONCLUSION: Stavudine
      associated toxicities continued to accumulate during the second year of ART,
      especially peripheral neuropathy and lipodystrophy and more so at increasing age.
      Our findings support investments for replacing stavudine in first-line regimens
      in sub-Saharan Africa.

PMID- 22848697
TI  - Association of adenovirus 36 infection with obesity and metabolic markers in
      humans: a meta-analysis of observational studies.
AB  - BACKGROUND: Several studies have shown that Adenovirus 36 (Ad36) influences the
      risk of obesity in humans. Clarifying the relationship between Ad36 infection and
      obesity could lead to more effective approaches for the management of obesity.
      The objective of this study was to conduct a meta-analysis to confirm the
      influence of Ad36 infection on obesity and metabolic markers.
      METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE and the Cochrane Library for
      pertinent articles (including their references) published between 1951 and April
      22, 2012. Only English language reports of original observational studies were
      included in this meta-analysis. Data extraction was performed independently by
      two reviewers. Weighted mean differences (WMDs) and pooled odds ratios (ORs) with
      95% confidence intervals (95% CIs) were calculated using the random effects
      model. Of 237 potentially relevant studies, 10 cross-sectional studies (n =
      2,870) conformed to the selection criteria. Pooled analysis showed that the WMD
      for BMI of Ad36 infection compared with non-infection was 3.19 (95% CI 1.44-4.93;
      P<0.001). Sensitivity analysis restricted to studies of adults yielded a similar
      result of 3.18 (95% CI 0.78-5.57; P = 0.009). The increased risk of obesity
      associated with Ad36 infection was also significant (OR: 1.9; 95% CI: 1.01-3.56;
      P = 0.047). No significant differences were found in relation to total
      cholesterol (P = 0.83), triglycerides (P = 0.64), HDL (P = 0.69), blood glucose
      (P = 0.08), waist circumstance (P = 0.09), and systolic blood pressure (P =
      0.25). CONCLUSION/SIGNIFICANCE: Ad36 infection was associated with the risk of
      obesity and weight gain, but was not associated with abnormal metabolic markers
      including waist circumstance. It suggests that Ad36 infection is more associated
      with accumulation of subcutaneous fat than that of visceral fat. The relationship
      between Ad36 and obesity should be assessed by further studies, including well
      designed prospective studies, to gain a better understanding of whether Ad36
      plays a role in the etiology of human obesity.

PMID- 22848699
TI  - Detritus quality controls macrophyte decomposition under different nutrient
      concentrations in a eutrophic shallow lake, North China.
AB  - Macrophyte decomposition is important for carbon and nutrient cycling in lake
      ecosystems. Currently, little is known about how this process responds to
      detritus quality and water nutrient conditions in eutrophic shallow lakes in
      which incomplete decomposition of detritus accelerates the lake
      terrestrialization process. In this study, we investigated the effects of
      detritus quality and water nutrient concentrations on macrophyte decomposition in
      Lake Baiyangdian, China, by analyzing the decomposition of three major aquatic
      plants at three sites with different pollution intensities (low, medium, and high
      pollution sites). Detritus quality refers to detritus nutrient contents as well
      as C:N, C:P, and N:P mass ratios in this study. Effects of detritus mixtures were
      tested by combining pairs of representative macrophytes at ratios of 75:25, 50:50
      and 25:75 (mass basis). The results indicate that the influence of species types
      on decomposition was stronger than that of site conditions. Correlation analysis
      showed that mass losses at the end of the experimental period were significantly
      controlled by initial detritus chemistry, especially by the initial phosphorus
      (P) content, carbon to nitrogen (C:N), and carbon to phosphorus (C:P) mass ratios
      in the detritus. The decomposition processes were also influenced by water
      chemistry. The NO(3)-N and NH(4)-N concentrations in the lake water retarded
      detritus mass loss at the low and high pollution sites, respectively. Net P
      mineralization in detritus was observed at all sites and detritus P release at
      the high pollution site was slower than at the other two sites. Nonadditive
      effects of mixtures tended to be species specific due to the different nutrient
      contents in each species. Results suggest that the nonadditive effects varied
      significantly among different sites, indicating that interactions between the
      detritus quality in species mixtures and site water chemistry may be another
      driver controlling decomposition in eutrophic shallow lakes.

PMID- 22848698
TI  - Next-generation sequencing of the porcine skeletal muscle transcriptome for
      computational prediction of microRNA gene targets.
AB  - BACKGROUND: MicroRNA are a class of small RNAs that regulate gene expression by
      inhibiting translation of protein encoding transcripts through targeting of a
      microRNA-protein complex by base-pairing of the microRNA sequence to cognate
      recognition sequences in the 3' untranslated region (UTR) of the mRNA. Target
      identification for a given microRNA sequence is generally accomplished by
      informatics analysis of predicted mRNA sequences present in the genome or in
      databases of transcript sequence for the tissue of interest. However, gene models
      for porcine skeletal muscle transcripts in current databases, specifically
      complete sequence of the 3' UTR, are inadequate for this exercise.
      METHODOLOGY/PRINCIPAL FINDINGS: To provide data necessary to identify gene
      targets for microRNA in porcine skeletal muscle, normalized cDNA libraries were
      sequenced using Roche 454 GS-FLX pyrosequencing and de novo assembly of
      transcripts enriched in the 3' UTR was performed using the MIRA sequence assembly
      program. Over 725 million bases of sequence were generated, which assembled into
      18,202 contigs. Sequence reads were mapped to a 3' UTR database containing
      porcine sequences. The 3' UTR that mapped to the database were examined to
      predict targets for previously identified microRNA that had been separately
      sequenced from the same porcine muscle sample used to generate the cDNA
      libraries. For genes with microRNA-targeted 3' UTR, KEGG pathways were
      computationally determined in order to identify potential functional effects of
      these microRNA-targeted transcripts. CONCLUSIONS: Through next-generation
      sequencing of transcripts expressed in skeletal muscle, mapping reads to a 3' UTR
      database, and prediction of microRNA target sites in the 3' UTR, our results
      identified genes expressed in porcine skeletal muscle and predicted the microRNA
      that target these genes. Additionally, identification of pathways regulated by
      these microRNA-targeted genes provides us with a set of genes that can be further
      evaluated for their potential role in skeletal muscle development and growth.

PMID- 22848700
TI  - Schistosoma japonicum UDP-glucose 4-epimerase protein is located on the tegument
      and induces moderate protection against challenge infection.
AB  - Schistosomiasis is an important global public health problem, as millions of
      people are at risk of acquiring this infection. An ideal method for sustainable
      control of schistosomiasis is using a vaccine alone or in combination with drugs.
      In the present study, we cloned the SjGALE gene and generated the expression
      product in E. coli. The expression level of SjGALE during different developmental
      stages of S. japonicum was evaluated by real-time RT-PCR and western blotting.
      Immunolocalization indicated that the protein was mainly located on the tegument
      of the parasite. Infection of rSjGALE-immunized mice demonstrated a 34% and 49%
      reduction of the mean worm burden and liver egg burden, respectively, in two
      independent experiments, indicating immune protection. The liver egg count from
      each female adult worm was significantly reduced by 63% in the two trials. The
      cytokine profile and IgG isotype analysis demonstrated the induction of a Th1
      immune profile in response to immunization with this protein, further suggesting
      protection against infection. In conclusion, these findings indicated that SjGALE
      is a potential vaccine against S. japonicum.

PMID- 22848701
TI  - The importance of 1H-nuclear magnetic resonance spectroscopy for reference
      standard validation in analytical sciences.
AB  - This paper highlights the importance of recording at least a (1)H nuclear
      magnetic resonance (NMR) spectrum to verify identity of standards used in
      analyses of organic materials irrespective of source. We show the importance of
      this approach with an example of a quantitative high-performance liquid
      chromatography (HPLC) study undertaken with green tea extracts that required the
      use of several polyphenols as standards. In the course of the study one of these
      standards [(-)-epigallocatechin, EGC], although having the physical appearance
      and appropriate HPLC chromatographic behavior of EGC, proved by (1)H-NMR to be a
      completely different class of molecule. For us, this raised significant questions
      concerning validity of many published pieces of research that used quantitative
      HPLC methods without first performing rigorous validation of the employed
      standards prior to their use. This paper clearly illustrates the importance of
      validation of all standards used in analysis of organic materials by recording at
      least a (1)H-NMR spectrum of them prior to their use.

PMID- 22848702
TI  - Medulloblastoma exosome proteomics yield functional roles for extracellular
      vesicles.
AB  - Medulloblastomas are the most prevalent malignant pediatric brain tumors.
      Survival for these patients has remained largely the same for approximately 20
      years, and our therapies for these cancers cause significant health, cognitive,
      behavioral and developmental sequelae for those who survive the tumor and their
      treatments. We obviously need a better understanding of the biology of these
      tumors, particularly with regard to their migratory/invasive behaviors, their
      proliferative propensity, and their abilities to deflect immune responses.
      Exosomes, virus-sized membrane vesicles released extracellularly from cells after
      formation in, and transit thru, the endosomal pathway, may play roles in
      medulloblastoma pathogenesis but are as yet unstudied in this disease. Here we
      characterized exosomes from a medulloblastoma cell line with biochemical and
      proteomic analyses, and included characterization of patient serum exosomes.
      Further scrutiny of the proteomic data suggested functional properties of the
      exosomes that are relevant to medulloblastoma tumor biology, including their
      roles as proliferation stimulants, their activities as attractants for tumor cell
      migration, and their immune modulatory impacts on lymphocytes. Aspects of this
      held true for exosomes from other medulloblastoma cell lines as well.
      Additionally, pathway analyses suggested a possible role for the transcription
      factor hepatocyte nuclear factor 4 alpha (HNF4A); however, inhibition of the
      protein's activity actually increased D283MED cell proliferation/clonogenecity,
      suggesting that HNF4A may act as a tumor suppressor in this cell line. Our work
      demonstrates that relevant functional properties of exosomes may be derived from
      appropriate proteomic analyses, which translate into mechanisms of tumor
      pathophysiology harbored in these extracellular vesicles.

PMID- 22848703
TI  - Fc-epsilon-RI, the high affinity IgE-receptor, is robustly expressed in the upper
      gastrointestinal tract and modulated by mucosal inflammation.
AB  - BACKGROUND: The role of the high affinity IgE receptor, FcepsilonRI, in IgE
      mediated immune responses of the gastrointestinal (GI) mucosa is poorly
      understood. Currently, a detailed characterization of FcepsilonRI expression
      throughout the human gut is lacking. The aim of this study was to define the
      expression pattern of FcepsilonRI in the GI tract. METHODS/PRINCIPAL FINDINGS: We
      compared FcepsilonRI expression in children with gastritis/esophagitis (n = 10),
      celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal
      mucosa (n = 5). The alpha-subunit of FcepsilonRI (FcepsilonRIalpha), detected by
      immunohistochemistry, was found on cells infiltrating the mucosa of the
      esophagus, the stomach, and the duodenum, but was rarely detected in more distal
      sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus,
      stomach, duodenum, colon, and rectum biopsies revealed that FcepsilonRIalpha and 
      beta expression levels decreased towards the distal intestine. mRNA transcripts
      of the common Fc-receptor-gamma chain were present in the entire GI mucosa.
      Double-immunofluorescence staining of esophageal specimens confirmed that
      FcepsilonRIalpha was expressed on intraepithelial mast cells and Langerhans
      cells. The mRNA expression levels of the alpha, beta, and gamma subunits of
      FcepsilonRI did not correlate with total serum IgE but were associated with
      mucosal inflammation. CONCLUSION/SIGNIFICANCE: Our data define the upper GI tract
      as the main site for IgE-mediated immune activation via FcepsilonRI. Tissue mRNA
      levels of FcepsilonRIalpha are regulated by inflammatory conditions rather than
      serum IgE, indicating that FcepsilonRI might also play a role in pathologies
      other than allergy.

PMID- 22848705
TI  - Assessing the risk that Phytophthora melonis can develop a point mutation
      (V1109L) in CesA3 conferring resistance to carboxylic acid amide fungicides.
AB  - The risk that the plant pathogen Phytophthora melonis develops resistance to
      carboxylic acid amide (CAA) fungicides was determined by measuring baseline
      sensitivities of field isolates, generating resistant mutants, and measuring the
      fitness of the resistant mutants. The baseline sensitivities of 80 isolates to
      flumorph, dimethomorph and iprovalicarb were described by unimodal curves, with
      mean EC(50) values of 0.986 (+/-0.245), 0.284 (+/-0.060) and 0.327 (+/-0.068)
      ug/ml, respectively. Seven isolates with different genetic background (as
      indicated by RAPD markers) were selected to generate CAA-resistance. Fifty-five
      resistant mutants were obtained from three out of seven isolates by spontaneous
      selection and UV-mutagenesis with frequencies of 1*10(-7) and 1*10(-6),
      respectively. CAA-resistance was stable for all mutants. The resistance factors
      of these mutants ranged from 7 to 601. The compound fitness index (CFI  = 
      mycelial growth * zoospore production * pathogenicity) was often lower for the
      CAA-resistant isolates than for wild-type isolates, suggesting that the risk of
      P. melonis developing resistance to CAA fungicides is low to moderate. Among the
      CAA-resistant isolates, a negative correlation between EC(50) values was found
      for iprovalicarb vs. flumorph and for iprovalicarb vs. dimethomorph. Comparison
      of the full-length cellulose synthase 3 (CesA3) between wild-type and CAA
      resistant isolates revealed only one point mutation at codon position 1109: a
      valine residue (codon GTG in wild-type isolates) was converted to leucine (codon
      CTG in resistant mutants). This represents a novel point mutation with respect to
      mutations in CesA3 conferring resistance to CAA fungicides. Based on this
      mutation, an efficient allelic-specific PCR (AS-PCR) method was developed for
      rapid detection of CAA-resistance in P. melonis populations.

PMID- 22848704
TI  - Probiotic bacteria regulate intestinal epithelial permeability in experimental
      ileitis by a TNF-dependent mechanism.
AB  - BACKGROUND: We previously showed that the probiotic mixture, VSL#3, prevents the
      onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with
      stimulation of epithelial-derived TNF. The aim of this study was to determine the
      mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to
      further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis.
      METHODS: Permeability was evaluated in SAMP mice prior to the onset of
      inflammation and during established disease by measuring transepithelial
      electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3
      conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins
      were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII
      expression measured in freshly isolated intestinal epithelial cells (IEC) from
      SAMP and control AKR mice. RESULTS: Culture with either VSL#3-CM or TNF resulted
      in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP
      with established disease, while addition of anti-TNF abrogated these effects.
      Modulation of the TJ proteins, claudin-2 and occludin, occurred with a
      significant decrease in claudin-2 and increase in occludin following stimulation
      with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea
      incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA
      expression decreased in young, and was elevated in inflamed, SAMP versus AKR
      mice. CONCLUSIONS: Our data demonstrate that the previously established efficacy
      of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic
      effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2
      and occludin, and overall improvement of intestinal permeability.

PMID- 22848706
TI  - To eat and not be eaten: modelling resources and safety in multi-species animal
      groups.
AB  - Using mixed-species bird flocks as an example, we model the payoffs for two types
      of species from participating in multi-species animal groups. Salliers feed on
      mobile prey, are good sentinels and do not affect prey capture rates of gleaners;
      gleaners feed on prey on substrates and can enhance the prey capture rate of
      salliers by flushing prey, but are poor sentinels. These functional types are
      known from various animal taxa that form multi-species associations. We model
      costs and benefits of joining groups for a wide range of group compositions under
      varying abundances of two types of prey-prey on substrates and mobile prey. Our
      model predicts that gleaners and salliers show a conflict of interest in multi
      species groups, because gleaners benefit from increasing numbers of salliers in
      the group, whereas salliers benefit from increasing gleaner numbers. The model
      also predicts that the limits to size and variability in composition of multi
      species groups are driven by the relative abundance of different types of prey,
      independent of predation pressure. Our model emphasises resources as a primary
      driver of temporal and spatial group dynamics, rather than reproductive activity
      or predation per se, which have hitherto been thought to explain patterns of
      multi-species group formation and cohesion. The qualitative predictions of the
      model are supported by empirical patterns from both terrestrial and marine multi
      species groups, suggesting that similar mechanisms might underlie group dynamics
      in a range of taxa. The model also makes novel predictions about group dynamics
      that can be tested using variation across space and time.

PMID- 22848707
TI  - Epstein-Barr virus immortalization of human B-cells leads to stabilization of
      hypoxia-induced factor 1 alpha, congruent with the Warburg effect.
AB  - BACKGROUND: Epstein-Barr virus (EBV) encodes six nuclear transformation
      associated proteins that induce extensive changes in cellular gene expression and
      signaling and induce B-cell transformation. The role of HIF1A in EBV-induced B
      cell immortalization has not been previously studied. METHODS AND FINDINGS: Using
      Western blotting and Q-PCR, we found that HIF1A protein is stabilized in EBV
      transformed lymphoblastoid cells. Western blotting, GST pulldown assays, and
      immunoprecipitation showed that EBV-encoded nuclear antigens EBNA-5 and EBNA-3
      bind to prolylhydroxylases 1 and 2, respectively, thus inhibiting HIF1A
      hydroxylation and degradation. Immunostaining and Q-PCR showed that the
      stabilized HIF1A translocates to the nucleus, forms a heterodimer with ARNT, and
      transactivates several genes involved in aerobic glycolysis. Using biochemical
      assays and Q-PCR, we also found that lymphoblastoid cells produce high levels of
      lactate, lactate dehydrogenase and pyruvate. CONCLUSIONS: Our data suggest that
      activation of the aerobic glycolytic pathway, corresponding to the Warburg
      effect, occurs in EBV-transformed lymphoblastoid cells, in contrast to mitogen
      activated B-cells.

PMID- 22848708
TI  - Ischemia/reperfusion-induced MKP-3 impairs endothelial NO formation via
      inactivation of ERK1/2 pathway.
AB  - Mitogen-activated protein kinase phosphatases (MKPs) are a family of dual
      specificity phosphatases. Endothelial cells express multiple MKP family members,
      such as MKP-3. However, the effects of MKP-3 on endothelial biological processes
      have not yet been fully elucidated. Here, we address the association between MKP
      3 and endothelial Nitric oxide (NO) formation under ischemia/reperfusion (IS/RP)
      condition. Human umbilical vein endothelial cells (HUVECs) were subjected to
      IS/RP treatment. The MKP-3 expression and NO formation were examined. IS/RP
      induced endothelial MKP-3 expression and inhibited eNOS expression and NO
      formation, accompanied by an increase of endothelial apoptosis. The siRNA
      experiments showed that MKP-3 was an important mediator in impairing eNOS
      expression and NO production in endothelial cells. Transfection of HUVECs with
      constitutively active ERK plasmids suggested that the above mentioned effect of
      MKP-3 was via inactivation of ERK1/2 pathway. Furthermore, impairment of eNOS
      expression was restored by treatment of histone deacetylase (HDAC) inhibitor and
      related to histone deacetylation and recruitment of HDAC1 to the eNOS promoter.
      Finally, Salvianolic acid A (SalA) markedly attenuated induction of MKP-3 and
      inhibition of eNOS expression and NO formation under endothelial IS/RP condition.
      Overall, these results for the first time demonstrated that IS/RP inhibited eNOS
      expression by inactivation of ERK1/2 and recruitment of HDAC1 to the gene
      promoter, leading to decreased NO formation through a MKP-3-dependent mechanism
      in endothelial cells, and SalA has therapeutic significance in protecting
      endothelial cells from impaired NO formation in response to IS/RP.

PMID- 22848709
TI  - Bone and energy metabolism parameters in professional cyclists during the Giro
      d'Italia 3-weeks stage race.
AB  - Cycling is a not weight-bearing activity and is known to induce bone resorption.
      Stage races are really strenuous endurance performances affecting the energy
      homeostasis. The recently highlighted link, in the co-regulation of bone and
      energy metabolism, demonstrates a central role for the equilibrium between
      carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to
      understand the acute physiological responses to a cycling stage race in terms of
      bone turnover and energy metabolism and the possible co-regulative mechanisms
      underlying their relationship. We studied nine professional cyclists engaged in
      2011 Giro d'Italia stage race. Pre-analytical and analytical phases tightly
      followed academic and anti-doping authority's recommendations. Bone and energy
      metabolism markers (bone alkaline phosphatase, tartrate-resistant acid
      phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin)
      and related hormones (cortisol and testosterone) were measured, by Sandwich
      Enzyme Immunoassays, at days -1 (pre-race), 12 and 22 during the race. The power
      output and the energy expenditure (mean and accumulated) were derived and
      correlated with the biochemical indexes. During the race, bone metabolism showed
      that an unbalance in behalf of resorption, which is enhanced, occurred along with
      a relative increase in the concentration of the undercarboxylated form of
      osteocalcin that was indirectly related to the enhanced energy expenditure,
      through adipokines modifications, with leptin decrease (high energy consumption)
      and adiponectin increase (optimization of energy expenditure). The exertion due
      to heavy effort induced a decrease of cortisol, while testosterone levels
      resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism
      is pushed towards resorption. A possible relationship between the bone and the
      energy metabolisms is suggested by the relative correlations among absolute and
      relative concentrations trends of undercarboxylated OC, adipokines
      concentrations, BMI, fat mass (%), power output and the derived energy
      expenditure.

PMID- 22848711
TI  - Genotypic homogeneity of multidrug resistant S. Typhimurium infecting distinct
      adult and childhood susceptibility groups in Blantyre, Malawi.
AB  - Nontyphoidal Salmonella (NTS) serovars are a common cause of bacteraemia in young
      children and HIV-infected adults in Malawi and elsewhere in sub-Saharan Africa.
      These patient populations provide diverse host-immune environments that have the
      potential to drive bacterial adaptation and evolution. We therefore investigated
      the diversity of 27 multidrug resistant (MDR) Salmonella Typhimurium strains
      isolated over 6 years (2002-2008) from HIV-infected adults and children and HIV
      uninfected children. Sequence reads from whole-genome sequencing of these
      isolates using the Illumina GA platform were mapped to the genome of the
      laboratory strain S. Typhimurium SL1344 excluding homoplastic regions that
      contained prophage and insertion elements. A phylogenetic tree generated from
      single nucleotide polymorphisms showed that all 27 strains clustered with the
      prototypical MDR strain D23580. There was no clustering of strains based on host
      HIV status or age, suggesting that these susceptible populations acquire S.
      Typhimurium from common sources or that isolates are transmitted freely between
      these populations. However, 7/14 of the most recent isolates (2006/2008) formed a
      distinct clade that branched off 22 SNPs away from the cluster containing earlier
      isolates. These data suggest that the MDR bacterial population is not static, but
      is undergoing microevolution which might result in further epidemiology change.

PMID- 22848710
TI  - The aromatase gene (CYP19A1) variants and circulating hepatocyte growth factor in
      postmenopausal women.
AB  - BACKGROUND: Estrogen and androgen have been linked to the regulation of
      circulating hepatocyte growth factor (HGF), an adipose tissue-derived cytokine.
      It is possible that the CYP19A1 gene which alters sex hormones production may
      influence HGF levels. We examined the association between the CYP19A1 gene
      variants and plasma HGF concentrations. DESIGN: We evaluated 45 common and
      putative functional variants of CYP19A1 and circulating levels of HGF among 260
      postmenopausal women who later developed colorectal cancer from the Women's
      Health Initiative Observational Cohort. As the distribution of HGF levels was
      highly skewed, we transformed HGF concentrations for all women into a log-,
      ranked-, or normal score-scale value. Multiple linear regression with adjustment
      for age was used to evaluate the associations. RESULTS: We observed an
      association between the rs7172156, rs1008805, rs6493494, rs749292, and rs11636639
      variants and HGF levels in ranked and normal score scales (corrected p values
      <=0.02), although the association of these 5 SNPs with log-scale HGF was not
      significant (corrected p values >=0.16). The associations remained unchanged
      after additional adjustment for hormone therapy use and estradiol levels. These 5
      SNPs, which were in linkage disequilibrium (pairwise D'>=97%, r(2)>=56%),
      constituted a block with 2 common haplotypes accounting for 82% frequency. The
      most common haplotype, TCCCA, was associated with lower ranked- or normal score
      transformed HGF levels (corrected p values <=0.001), whereas the second most
      common haplotype, CTTCA, was associated with higher ranked- or normal score
      transformed HGF levels (corrected p values <=0.02). CONCLUSION: Our findings of a
      potential association between the CYP19A1 variants and circulating HGF levels
      warrant confirmation in studies with larger sample size.

PMID- 22848712
TI  - Cognitive dysfunction in early multiple sclerosis: altered centrality derived
      from resting-state functional connectivity using magneto-encephalography.
AB  - BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) is frequent. Insight
      into underlying mechanisms would help to develop therapeutic strategies.
      OBJECTIVE: To explore the relationship of cognitive performance to patterns of
      nodal centrality derived from magneto-encephalography (MEG). METHODS: 34 early
      relapsing-remitting MS patients (median EDSS 2.0) and 28 age- and gender-matched
      healthy controls (HC) had a MEG, a neuropsychological assessment and structural
      MRI. Resting-state functional connectivity was determined by the synchronization
      likelihood. Eigenvector Centrality (EC) was used to quantify for each sensor its
      connectivity and importance within the network. A cognition-score was calculated,
      and normalized grey and white matter volumes were determined. EC was compared per
      sensor and frequency band between groups using permutation testing, and related
      to cognition. RESULTS: Patients had lower grey and white matter volumes than HC,
      male patients lower cognitive performance than female patients. In HC, EC
      distribution showed highest nodal centrality over bi-parietal sensors ("hubs").
      In patients, nodal centrality was even higher bi-parietally (theta-band) but
      markedly lower left temporally (upper alpha- and beta-band). Lower cognitive
      performance correlated to decreased nodal centrality over left temporal (lower
      alpha-band) and right temporal (beta-band) sensors, and to increased nodal
      centrality over right parieto-temporal sensors (beta-band). Network changes were
      most pronounced in male patients. CONCLUSIONS: Partial functional disconnection
      of the temporal regions was associated with cognitive dysfunction in MS;
      increased centrality in parietal hubs may reflect a shift from temporal to
      possibly less efficient parietal processing. To better understand patterns and
      dynamics of these network changes, longitudinal studies are warranted, also
      addressing the influence of gender.

PMID- 22848713
TI  - IFN-gamma signaling to astrocytes protects from autoimmune mediated neurological
      disability.
AB  - Demyelination and axonal degeneration are determinants of progressive
      neurological disability in patients with multiple sclerosis (MS). Cells resident
      within the central nervous system (CNS) are active participants in development,
      progression and subsequent control of autoimmune disease; however, their
      individual contributions are not well understood. Astrocytes, the most abundant
      CNS cell type, are highly sensitive to environmental cues and are implicated in
      both detrimental and protective outcomes during autoimmune demyelination.
      Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice
      expressing signaling defective dominant-negative interferon gamma (IFN-gamma)
      receptors on astrocytes to determine the influence of inflammation on astrocyte
      activity. Inhibition of IFN-gamma signaling to astrocytes did not influence
      disease incidence, onset, initial progression of symptoms, blood brain barrier
      (BBB) integrity or the composition of the acute CNS inflammatory response.
      Nevertheless, increased demyelination at peak acute disease in the absence of IFN
      gamma signaling to astrocytes correlated with sustained clinical symptoms.
      Following peak disease, diminished clinical remission, increased mortality and
      sustained astrocyte activation within the gray matter demonstrate a critical role
      of IFN-gamma signaling to astrocytes in neuroprotection. Diminished disease
      remission was associated with escalating demyelination, axonal degeneration and
      sustained inflammation. The CNS infiltrating leukocyte composition was not
      altered; however, decreased IL-10 and IL-27 correlated with sustained disease.
      These data indicate that astrocytes play a critical role in limiting CNS
      autoimmune disease dependent upon a neuroprotective signaling pathway mediated by
      engagement of IFN-gamma receptors.

PMID- 22848714
TI  - Higher rates of Clostridium difficile infection among smokers.
AB  - OBJECTIVES: Cigarette smoking has been shown to be related to inflammatory bowel
      disease. We investigated whether smoking affected the probability of developing
      Clostridium difficile infection (CDI). METHODS: We conducted a longitudinal study
      of 16,781 older individuals from the nationally representative Health and
      Retirement Study. Data were linked to files from the Centers for Medicare and
      Medicaid Services. RESULTS: Overall, the rate of CDI in older individuals was
      220.6 per 100,000 person-years (95% CI 193.3, 248.0). Rates of CDI were
      281.6/100,000 person-years in current smokers, 229.0/100,000 in former smokers
      and 189.1/100,000 person-years in never smokers. The odds of CDI were 33% greater
      in former smokers (95% CI: 8%, 65%) and 80% greater in current smokers (95% CI:
      33%, 145%) when compared to never smokers. When the number of CDI-related visits
      was evaluated, current smokers had a 75% increased rate of CDI compared to never
      smokers (95% CI: 15%, 167%). CONCLUSIONS: Smoking is associated with developing a
      Clostridium difficile infection. Current smokers have the highest risk, followed
      by former smokers, when compared to rates of infection in never smokers.

PMID- 22848715
TI  - Ribavirin exerts differential effects on functions of Cd4+ Th1, Th2, and
      regulatory T cell clones in hepatitis C.
AB  - Ribavirin improves outcomes of therapy in chronic hepatitis C but its mode of
      action has still remained unclear. Since ribavirin has been proposed to modulate
      the host's T cell responses, we studied its direct effects on CD4(+) T cell
      clones with diverse functional polarization which had been generated from
      patients with chronic hepatitis C. We analysed in vitro proliferation ([(3)H]
      thymidine uptake) and cytokine responses (IL-10, IFN-gamma) at varying
      concentrations of ribavirin (0-10 ug/ml) in 8, 9 and 7 CD4(+) TH1, TH2 and
      regulatory T cell (Treg) clones, respectively. In co-culture experiments, we
      further determined effects of ribarivin on inhibition of TH1 and TH2 effector
      cells by Treg clones. All clones had been generated from peripheral blood of
      patients with chronic hepatitis C in the presence of HCV core protein. Ribavirin
      enhanced proliferation of T effector cells and increased production of IFN-gamma
      in TH1 clones, but had only little effect on IL-10 secretion in TH2 clones.
      However, ribavirin markedly inhibited IL-10 release in Treg clones in a dose
      dependent fashion. These Treg clones suppressed proliferation of T effector
      clones by their IL-10 secretion, and in co-culture assays ribavirin reversed Treg
      mediated suppression of T effector cells. Our in vitro data suggest that--in
      addition to its immunostimulatory effects on TH1 cells--ribavirin can inhibit
      functions of HCV-specific Tregs and thus reverses Treg-mediated suppression of T
      effector cells in chronic hepatitis C.

PMID- 22848716
TI  - Kinetic and dynamic computational model-based characterization of new proteins in
      mice: application to interferon alpha linked to apolipoprotein A-I.
AB  - Interferon alpha linked to apolipoprotein A-I has been recently proposed as an
      improved interferon-based therapy. In the present study, we aimed to develop a
      computational model to gain further insight into the in vivo behaviour of this
      new fusion protein. In order to facilitate in vivo evaluation of interferon and
      the fusion protein without altering their biological properties, green
      fluorescent protein was incorporated into their structures. Kinetic and dynamic
      behaviour of both compounds was successfully described after plasmid hydrodynamic
      administration and in situ synthesis of the studied proteins. Results from the
      modelling exercise showed that apolipoprotein A-I conferred a modified kinetic
      behaviour, varying molecule distribution and prolonging half-life without
      altering liver dynamic performance. However, differences in the gene expression
      activity were observed at brain level between both compounds. Those differences
      could be explained by modifications in the dynamic, but also in the
      biodistribution properties, which would be worth evaluating in future
      experiments. Therefore, the modelling approach provided a global comprehension of
      a complex system and allowed us to compare the in vivo behaviour of both
      compounds and to identify critical aspects that might be important to understand
      the system better and suggests a need for new model-based experiments.

PMID- 22848717
TI  - Influence of GABA(A) receptor alpha subunit isoforms on the benzodiazepine
      binding site.
AB  - Classical benzodiazepines, such as diazepam, interact with
      alpha(x)beta(2)gamma(2) GABA(A) receptors, x = 1, 2, 3, 5 and modulate their
      function. Modulation of different receptor isoforms probably results in selective
      behavioural effects as sedation and anxiolysis. Knowledge of differences in the
      structure of the binding pocket in different receptor isoforms is of interest for
      the generation of isoform-specific ligands. We studied here the interaction of
      the covalently reacting diazepam analogue 3-NCS with
      alpha(1)S204Cbeta(2)gamma(2), alpha(1)S205Cbeta(2)gamma(2) and
      alpha(1)T206Cbeta(2)gamma(2) and with receptors containing the homologous
      mutations in alpha(2)beta(2)gamma(2), alpha(3)beta(2)gamma(2),
      alpha(5)beta(1/2)gamma(2) and alpha(6)beta(2)gamma(2). The interaction was
      studied using radioactive ligand binding and at the functional level using
      electrophysiological techniques. Both strategies gave overlapping results. Our
      data allow conclusions about the relative apposition of
      alpha(1)S204Cbeta(2)gamma(2), alpha(1)S205Cbeta(2)gamma(2) and
      alpha(1)T206Cbeta(2)gamma(2) and homologous positions in alpha(2), alpha(3),
      alpha(5) and alpha(6) with C-atom adjacent to the keto-group in diazepam.
      Together with similar data on the C-atom carrying Cl in diazepam, they indicate
      that the architecture of the binding site for benzodiazepines differs in each
      GABA(A) receptor isoform alpha(1)beta(2)gamma(2), alpha(2)beta(2)gamma(2),
      alpha(3)beta(2)gamma(2), alpha(5)beta(1/2)gamma(2) and alpha(6)beta(2)gamma(2).

PMID- 22848718
TI  - A modular toolset for recombination transgenesis and neurogenetic analysis of
      Drosophila.
AB  - Transgenic Drosophila have contributed extensively to our understanding of
      nervous system development, physiology and behavior in addition to being valuable
      models of human neurological disease. Here, we have generated a novel series of
      modular transgenic vectors designed to optimize and accelerate the production and
      analysis of transgenes in Drosophila. We constructed a novel vector backbone,
      pBID, that allows both phiC31 targeted transgene integration and incorporates
      insulator sequences to ensure specific and uniform transgene expression. Upon
      this framework, we have built a series of constructs that are either backwards
      compatible with existing restriction enzyme based vectors or utilize Gateway
      recombination technology for high-throughput cloning. These vectors allow for
      endogenous promoter or Gal4 targeted expression of transgenic proteins with or
      without fluorescent protein or epitope tags. In addition, we have generated
      constructs that facilitate transgenic splice isoform specific RNA inhibition of
      gene expression. We demonstrate the utility of these constructs to analyze
      proteins involved in nervous system development, physiology and neurodegenerative
      disease. We expect that these reagents will facilitate the proficiency and
      sophistication of Drosophila genetic analysis in both the nervous system and
      other tissues.

PMID- 22848719
TI  - Synergy between vancomycin and nafcillin against Staphylococcus aureus in an in
      vitro pharmacokinetic/pharmacodynamic model.
AB  - INTRODUCTION: Continued pressure from glycopeptide use has led to non-susceptible
      strains of Staphylococcus aureus including heterogeneously vancomycin
      intermediate S. aureus (hVISA). Infections with hVISA are associated with poor
      patient outcomes, thus incentivizing novel treatments. Evidence suggests that
      vancomycin and anti-staphylococcal penicillin susceptibility are inversely
      related which indicates that the use of this combination may be particularly
      useful against methicillin-resistant S. aureus with reduced susceptibility to
      vancomycin, such as hVISA. The aim of this study was to evaluate the potential
      for synergy between vancomycin and nafcillin against hVISA. METHODS: Twenty-five
      hVISA strains were evaluated for vancomycin and nafcillin minimum inhibitory
      concentration (MIC) by broth microdilution in duplicate. Potential for synergy
      was assessed by time-kill at 1/2x MIC in triplicate. Five strains were chosen,
      representing the range nafcillin MIC's available in the cohort -4, 16, 64, 128,
      and 256 ug/mL, and were run in an in vitro pharmacokinetic/pharmacodynamic
      (PK/PD) model in duplicate over 72 hours to evaluate the potential of the
      combination with simulated human pharmacokinetics. In addition, 4 fully
      glycopeptide susceptible strains of S. aureus including 2 methicillin-susceptible
      (MSSA) and 2 methicillin-resistant (MRSA) were run in the PK/PD model for
      comparison. RESULTS: In the time-kill, 92% of strains (23 of 25) displayed
      synergy with the combination of vancomycin and nafcillin. In the PK/PD model, all
      five strains of hVISA showed an improvement in overall activity (P<=0.004) and
      organism burden at 72 hours (P<=0.001) with the combination compared to either
      drug alone. The combination was also successful against both MRSA and MSSA in
      overall activity (P<=0.009) and organism burden at 72 hours (P<=0.016), though
      the magnitude of the effect was diminished against MSSA. CONCLUSIONS: The
      combination of vancomycin and nafcillin significantly improved antibacterial
      activity against hVISA, MRSA, and MSSA compared to either drug alone.

PMID- 22848721
TI  - Analysis of monensin sensitivity in Toxoplasma gondii reveals autophagy as a
      mechanism for drug induced death.
AB  - Understanding the mechanisms by which anti-parasitic drugs alter the physiology
      and ultimately kill is an important area of investigation. Development of novel
      parasitic drugs, as well as the continued utilization of existing drugs in the
      face of resistant parasite populations, requires such knowledge. Here we show
      that the anti-coccidial drug monensin kills Toxoplasma gondii by inducing
      autophagy in the parasites, a novel mechanism of cell death in response to an
      antimicrobial drug. Monensin treatment results autophagy, as shown by
      translocation of ATG8 to autophagosomes, as well as causing marked morphological
      changes in the parasites' mitochondria. Use of the autophagy inhibitor 3
      methyladenine blocks autophagy and mitochondrial alterations, and enhances
      parasite survival, in monensin-exposed parasites, although it does not block
      other monensin-induced effects on the parasites, such as late S-phase cell cycle
      arrest. Monensin does not induce autophagy in a parasite strain deficient in the
      mitochondrial DNA repair enzyme TgMSH-1 an enzyme that mediates monensin-induced
      late S-phase arrest. TgMSH-1 therefore either mediates cell cycle arrest and
      autophagy independently, or autophagy occurs downstream of cell cycle arrest in a
      manner analogous to apoptosis of cells arrested in G(2) of the cell cycle.
      Overall, our results point to autophagy as a potentially important mode of cell
      death of protozoan parasites in response to antimicrobial drugs and indicate that
      disruption of the autophagy pathway could result in drug resistance.

PMID- 22848720
TI  - Local loperamide injection reduces mechanosensitivity of rat cutaneous,
      nociceptive C-fibers.
AB  - Loperamide reverses signs of mechanical hypersensitivity in an animal model of
      neuropathic pain suggesting that peripheral opioid receptors may be suitable
      targets for the treatment of neuropathic pain. Since little is known about
      loperamide effects on the responsiveness of primary afferent nerve fibers, in
      vivo electrophysiological recordings from unmyelinated afferents innervating the
      glabrous skin of the hind paw were performed in rats with an L5 spinal nerve
      lesion or sham surgery. Mechanical threshold and responsiveness to suprathreshold
      stimulation were tested before and after loperamide (1.25, 2.5 and 5 ug in 10 ul)
      or vehicle injection into the cutaneous receptive field. Loperamide dose
      dependently decreased mechanosensitivity in unmyelinated afferents of nerve
      injured and sham animals, and this effect was not blocked by naloxone
      pretreatment. We then investigated loperamide effects on nerve conduction by
      recording compound action potentials in vitro during incubation of the sciatic
      nerve with increasing loperamide concentrations. Loperamide dose-dependently
      decreased compound action potentials of myelinated and unmyelinated fibers (ED50
      = 8 and 4 ug/10 ul, respectively). This blockade was not prevented by pre
      incubation with naloxone. These results suggest that loperamide reversal of
      behavioral signs of neuropathic pain may be mediated, at least in part, by
      mechanisms independent of opioid receptors, most probably by local anesthetic
      actions.

PMID- 22848722
TI  - Uptake of voluntary counselling and testing among young people participating in
      an HIV prevention trial: comparison of opt-out and opt-in strategies.
AB  - BACKGROUND: HIV voluntary counselling and testing (VCT) is an integral component
      of HIV prevention and treatment programmes. However, testing coverage in sub
      Saharan Africa is still low, particularly among young people. As treatment
      becomes more widely available, strategies to expand VCT coverage are critically
      important. We compare VCT uptake using two delivery strategies (opt-in and opt
      out) within the MEMA kwa Vijana trial in 20 communities in northwest Tanzania.
      METHODS: We analysed data from 12,590 young persons (median (IQR) age 22 years
      (20-23)) to assess the effect of delivery strategy on VCT uptake. Ten communities
      used an opt-in approach and 10 used opt-out, balanced across intervention and
      control. Conditional logistic regression was used to examine factors associated
      with uptake within each strategy. RESULTS: VCT uptake was significantly higher
      with the opt-out approach (90.9% vs 60.5%, prevalence ratio = 1.51, CI = 1.41
      1.62). Among females, uptake in the opt-out approach was associated with
      decreased knowledge of HIV acquisition, sex with a casual partner, and being HSV
      2 seronegative; among males, uptake was associated with lower education and
      increasing lifetime partners. In contrast, uptake using the opt-in approach
      varied by ethnic group, religion and marital status, and increased with
      increasing knowledge of STI acquisition (males) or pregnancy prevention
      (females). CONCLUSION: VCT uptake among young people was extremely high when
      offered an opt-out strategy. Sociodemographic and knowledge factors affected
      uptake in different ways depending on delivery strategy. Increased knowledge may
      increase young persons' self-efficacy, which may have a different impact on
      testing uptake, depending on the approach used.

PMID- 22848723
TI  - Squaring the circle. Social and environmental implications of pre-pottery
      neolithic building technology at Tell Qarassa (South Syria).
AB  - We present the results of the microstratigraphic, phytolith and wood charcoal
      study of the remains of a 10.5 ka roof. The roof is part of a building excavated
      at Tell Qarassa (South Syria), assigned to the Pre-Pottery Neolithic B period
      (PPNB). The Pre-Pottery Neolithic (PPN) period in the Levant coincides with the
      emergence of farming. This fundamental change in subsistence strategy implied the
      shift from mobile to settled aggregated life, and from tents and huts to hard
      buildings. As settled life spread across the Levant, a generalised transition
      from round to square buildings occurred, that is a trademark of the PPNB period.
      The study of these buildings is fundamental for the understanding of the ever
      stronger reciprocal socio-ecological relationship humans developed with the local
      environment since the introduction of sedentism and domestication. Descriptions
      of buildings in PPN archaeological contexts are usually restricted to the
      macroscopic observation of wooden elements (posts and beams) and mineral
      components (daub, plaster and stone elements). Reconstructions of microscopic and
      organic components are frequently based on ethnographic analogy. The direct study
      of macroscopic and microscopic, organic and mineral, building components
      performed at Tell Qarassa provides new insights on building conception,
      maintenance, use and destruction. These elements reflect new emerging paradigms
      in the relationship between Neolithic societies and the environment. A square
      building was possibly covered here with a radial roof, providing a glance into a
      topologic shift in the conception and understanding of volumes, from round-based
      to square-based geometries. Macroscopic and microscopic roof components indicate
      buildings were conceived for year-round residence rather than seasonal mobility.
      This implied performing maintenance and restoration of partially damaged
      buildings, as well as their adaptation to seasonal variability.

PMID- 22848724
TI  - CB1 receptor autoradiographic characterization of the individual differences in
      approach and avoidance motivation.
AB  - Typically, approach behaviour is displayed in the context of moving towards a
      desired goal, while avoidance behaviour is displayed in the context of moving
      away from threatening or novel stimuli. In the current research, we detected
      three sub-populations of C57BL/6J mice that spontaneously responded with
      avoiding, balancing or approaching behaviours in the presence of the same
      conflicting stimuli. While the balancing animals reacted with balanced responses
      between approach and avoidance, the avoiding or approaching animals exhibited
      inhibitory or advance responses towards one of the conflicting inputs,
      respectively. Individual differences in approach and avoidance motivation might
      be modulated by the normal variance in the level of functioning of different
      systems, such as endocannabinoid system (ECS). The present research was aimed at
      analysing the ECS involvement on approach and avoidance behavioural processes. To
      this aim, in the three selected sub-populations of mice that exhibited avoiding
      or balancing or approaching responses in an approach/avoidance Y-maze we analysed
      density and functionality of CB(1) receptors as well as enzyme fatty acid amide
      hydrolase activity in different brain regions, including the networks
      functionally responsible for emotional and motivational control. The main finding
      of the present study demonstrates that in both approaching and avoiding animals
      higher CB(1) receptor density in the amygdaloidal centro-medial nuclei and in the
      hypothalamic ventro-medial nucleus was found when compared with the CB(1)
      receptor density exhibited by the balancing animals. The characterization of the
      individual differences to respond in a motivationally based manner is relevant to
      clarify how the individual differences in ECS activity are associated with
      differences in motivational and affective functioning.

PMID- 22848725
TI  - Mannose-binding lectin deficiency is associated with myocardial infarction: the
      HUNT2 study in Norway.
AB  - OBJECTIVES: Mannose-binding lectin (MBL) and ficolins activate the complement
      cascade, which is involved in atherogenesis. Based on a pilot study, we
      hypothesized that functional polymorphisms in the MBL gene (MBL2) leading to
      dysfunctional protein are related to development of myocardial infarction (MI).
      The aim of the present study was to study polymorphisms in MBL2 and ficolin genes
      in relation to the risk of MI. METHODS AND RESULTS: Using the population-based
      HUNT Study in Norway, 57,133 persons were followed up for a first-time MI from
      1995-1997 until the end of 2008. The 370 youngest MI patients were matched by age
      (range 29-62 years) and gender to 370 controls. A younger population was selected
      because disease in this group might be less dependent on non-genetic risk
      factors. The study size was based on power calculation. Polymorphisms in MBL2 and
      in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by
      pyrosequencing and related to the risk of MI, estimated as odds ratios (OR).
      Functional haplotypes were analyzed and stringent alpha levels of significance
      were set by permutation testing. Variant MBL2 haplotypes causing MBL deficiency
      were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29-3.24).
      Adjustments for conventional cardiovascular risk factors did not substantially
      influence the association. The ficolins were not associated with MI risk.
      CONCLUSION: In a young to middle aged and relatively healthy Caucasian
      population, MBL2 variants related to functional MBL deficiency were associated
      with a doubling of the risk for MI, independent of conventional risk factors.
      This supports that MBL deficiency may lead to increased atherosclerosis or
      development of vulnerable plaques.

PMID- 22848726
TI  - The cellular immune response of the pea aphid to foreign intrusion and symbiotic
      challenge.
AB  - Recent studies suggest that the pea aphid (Acyrthosiphon pisum) has low immune
      defenses. However, its immune components are largely undescribed, and notably,
      extensive characterization of circulating cells has been missing. Here, we report
      characterization of five cell categories in hemolymph of adults of the LL01 pea
      aphid clone, devoid of secondary symbionts (SS): prohemocytes, plasmatocytes,
      granulocytes, spherulocytes and wax cells. Circulating lipid-filed wax cells are
      rare; they otherwise localize at the basis of the cornicles. Spherulocytes, that
      are likely sub-cuticular sessile cells, are involved in the coagulation process.
      Prohemocytes have features of precursor cells. Plasmatocytes and granulocytes,
      the only adherent cells, can form a layer in vivo around inserted foreign objects
      and phagocytize latex beads or Escherichia coli bacteria injected into aphid
      hemolymph. Using digital image analysis, we estimated that the hemolymph from one
      LL01 aphid contains about 600 adherent cells, 35% being granulocytes. Among aphid
      YR2 lines differing only in their SS content, similar results to LL01 were
      observed for YR2-Amp (without SS) and YR2-Ss (with Serratia symbiotica), while
      YR2-Hd (with Hamiltonella defensa) and YR2(Ri) (with Regiella insecticola) had
      strikingly lower adherent hemocyte numbers and granulocyte proportions. The
      effect of the presence of SS on A. pisum cellular immunity is thus symbiont
      dependent. Interestingly, Buchnera aphidicola (the aphid primary symbiont) and
      all SS, whether naturally present, released during hemolymph collection, or
      artificially injected, were internalized by adherent hemocytes. Inside hemocytes,
      SS were observed in phagocytic vesicles, most often in phagolysosomes. Our
      results thus raise the question whether aphid symbionts in hemolymph are taken up
      and destroyed by hemocytes, or actively promote their own internalization, for
      instance as a way of being transmitted to the next generation. Altogether, we
      demonstrate here a strong interaction between aphid symbionts and immune cells,
      depending upon the symbiont, highlighting the link between immunity and
      symbiosis.

PMID- 22848727
TI  - Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans
      and D. rerio.
AB  - The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a
      growing number of neurodegenerative diseases, including amyotrophic lateral
      sclerosis (ALS) and related dementia, but little is known about the neurotoxic
      mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models
      expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Delta or R521H) that
      reflect certain aspects of ALS including motor neuron degeneration, axonal
      deficits, and progressive paralysis. To explore the potential of our humanized
      transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant
      TDP-43 and FUS neuronal toxicity, we tested three compounds with potential
      neuroprotective properties: lithium chloride, methylene blue and riluzole. We
      identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in
      both our models. Our results indicate that methylene blue can rescue toxic
      phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction
      and oxidative stress.

PMID- 22848728
TI  - DNA polymorphisms and biocontrol of Bacillus antagonistic to citrus bacterial
      canker with indication of the interference of phyllosphere biofilms.
AB  - Citrus bacterial canker caused by Xanthomonas axonopodis pv. citri is a
      devastating disease resulting in significant crop losses in various citrus
      cultivars worldwide. A biocontrol agent has not been recommended for this
      disease. To explore the potential of bacilli native to Taiwan to control this
      disease, Bacillus species with a broad spectrum of antagonistic activity against
      various phytopathogens were isolated from plant potting mixes, organic compost
      and the rhizosphere soil. Seven strains TKS1-1, OF3-16, SP4-17, HSP1, WG6-14,
      TLB7-7, and WP8-12 showing superior antagonistic activity were chosen for
      biopesticide development. The genetic identity based on 16S rDNA sequences
      indicated that all seven native strains were close relatives of the B. subtilis
      group and appeared to be discrete from the B. cereus group. DNA polymorphisms in
      strains WG6-14, SP4-17, TKS1-1, and WP8-12, as revealed by repetitive sequence
      based PCR with the BOXA1R primers were similar to each other, but different from
      those of the respective Bacillus type strains. However, molecular typing of the
      strains using either tDNA-intergenic spacer regions or 16S-23S intergenic
      transcribed spacer regions was unable to differentiate the strains at the species
      level. Strains TKS1-1 and WG6-14 attenuated symptom development of citrus
      bacterial canker, which was found to be correlated with a reduction in
      colonization and biofilm formation by X. axonopodis pv. citri on leaf surfaces.
      The application of a Bacillus strain TKS1-1 endospore formulation to the leaf
      surfaces of citrus reduced the incidence of citrus bacterial canker and could
      prevent development of the disease.

PMID- 22848729
TI  - Dengue fever occurrence and vector detection by larval survey, ovitrap and
      MosquiTRAP: a space-time clusters analysis.
AB  - The use of vector surveillance tools for preventing dengue disease requires fine
      assessment of risk, in order to improve vector control activities. Nevertheless,
      the thresholds between vector detection and dengue fever occurrence are currently
      not well established. In Belo Horizonte (Minas Gerais, Brazil), dengue has been
      endemic for several years. From January 2007 to June 2008, the dengue vector
      Aedes (Stegomyia) aegypti was monitored by ovitrap, the sticky-trap MosquiTRAPTM
      and larval surveys in an study area in Belo Horizonte. Using a space-time scan
      for clusters detection implemented in SaTScan software, the vector presence
      recorded by the different monitoring methods was evaluated. Clusters of vectors
      and dengue fever were detected. It was verified that ovitrap and MosquiTRAP
      vector detection methods predicted dengue occurrence better than larval survey,
      both spatially and temporally. MosquiTRAP and ovitrap presented similar results
      of space-time intersections to dengue fever clusters. Nevertheless ovitrap
      clusters presented longer duration periods than MosquiTRAP ones, less acuratelly
      signalizing the dengue risk areas, since the detection of vector clusters during
      most of the study period was not necessarily correlated to dengue fever
      occurrence. It was verified that ovitrap clusters occurred more than 200 days
      (values ranged from 97.0+/-35.35 to 283.0+/-168.4 days) before dengue fever
      clusters, whereas MosquiTRAP clusters preceded dengue fever clusters by
      approximately 80 days (values ranged from 65.5+/-58.7 to 94.0+/-14. 3 days), the
      former showing to be more temporally precise. Thus, in the present cluster
      analysis study MosquiTRAP presented superior results for signaling dengue
      transmission risks both geographically and temporally. Since early detection is
      crucial for planning and deploying effective preventions, MosquiTRAP showed to be
      a reliable tool and this method provides groundwork for the development of even
      more precise tools.

PMID- 22848730
TI  - Inhibition of E2F1/CDK1 pathway attenuates neuronal apoptosis in vitro and
      confers neuroprotection after spinal cord injury in vivo.
AB  - Apoptosis of post-mitotic neurons plays a significant role in secondary tissue
      damage following traumatic spinal cord injury (SCI). Activation of E2F1-dependent
      transcription promotes expression of pro-apoptotic factors, including CDK1; this
      signal transduction pathway is believed to represent an important mechanism for
      the physiological or pathological neuronal cell death. However, a specific role
      for this pathway in neuronal apoptosis induced by SCI has not yet been reported.
      Here we demonstrate up-regulation of the E2F1/CDK1 pathway that is associated
      with neuronal apoptosis following impact SCI in rats. Expression of E2F1 and CDK1
      were robustly up-regulated as early as 15 min after injury and sustained until 3
      days post-injury. CDK1 activity and E2F1 downstream targets bim and c-Myb were
      significantly increased after SCI. Activation of E2F1/CDK1 signaling also was
      associated with death of neurons in vitro; this was attenuated by shRNA knockdown
      or pharmacological inhibition of the E2F1/CDK1 pathway. CR8, a novel and potent
      CDK1 inhibitor, blocked apoptosis of primary cortical neurons at low-micromolar
      concentrations. Moreover, SCI-induced up-regulation of E2F1/CDK1 and associated
      neuronal apoptosis was significantly attenuated by systemic injection of CR8 (1
      mg/kg, i.p.) at 5 min after injury. CR8 significantly decreased posttraumatic
      elevation of biochemical markers of apoptosis, such as products of caspase-3 and
      alpha-fodrin cleavage, as well as neuronal cell death, as indicated by TUNEL
      staining. Importantly, CR8 treatment also increased the number of surviving
      neurons at 5 weeks after injury. Together, these findings indicate that
      activation of the E2F1/CDK1 pathway contributes to the pathophysiology of SCI and
      that selective inhibition of this signaling cascade may represent an attractive
      therapeutic strategy.

PMID- 22848731
TI  - An NQO1-initiated and p53-independent apoptotic pathway determines the anti-tumor
      effect of tanshinone IIA against non-small cell lung cancer.
AB  - NQO1 is an emerging and promising therapeutic target in cancer therapy. This
      study was to determine whether the anti-tumor effect of tanshinone IIA (TSA) is
      NQO1 dependent and to elucidate the underlying apoptotic cell death pathways.
      NQO1(+) A549 cells and isogenically matched NQO1 transfected and negative H596
      cells were used to test the properties and mechanisms of TSA induced cell death.
      The in vivo anti-tumor efficacy and the tissue distribution properties of TSA
      were tested in tumor xenografted nude mice. We observed that TSA induced an
      excessive generation of ROS, DNA damage, and dramatic apoptotic cell death in
      NQO1(+) A549 cells and H596-NQO1 cells, but not in NQO1(-) H596 cells. Inhibition
      or silence of NQO1 as well as the antioxidant NAC markedly reversed TSA induced
      apoptotic effects. TSA treatment significantly retarded the tumor growth of A549
      tumor xenografts, which was significantly antagonized by dicoumarol co-treatment
      in spite of the increased and prolonged TSA accumulations in tumor tissues. TSA
      activated a ROS triggered, p53 independent and caspase dependent mitochondria
      apoptotic cell death pathway that is characterized with increased ratio of Bax to
      Bcl-xl, mitochondrial membrane potential disruption, cytochrome c release, and
      subsequent caspase activation and PARP-1 cleavage. The results of these findings
      suggest that TSA is a highly specific NQO1 target agent and is promising in
      developing as an effective drug in the therapy of NQO1 positive NSCLC.

PMID- 22848732
TI  - Non-invasive evaluation of cystic fibrosis related liver disease in adults with
      ARFI, transient elastography and different fibrosis scores.
AB  - BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is present in up to 30%
      of cystic fibrosis patients and can result in progressive liver failure.
      Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver
      fibrosis display an interesting diagnostic approach for CFLD detection. AIM: We
      evaluated transient elastography (TE), acoustic radiation force impulse imaging
      (ARFI), and fibrosis indices for CFLD detection. METHODS: TE and ARFI were
      performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI),
      and Forns' score were calculated. Healthy probands and patients with alcoholic
      liver cirrhosis served as controls. RESULTS: Fourteen CF patients met CFLD
      criteria, six had liver cirrhosis. Elastography acquisition was successful in
      >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar
      to CF patients without liver involvement. Cases with liver cirrhosis differed
      significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE:
      7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than
      individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002).
      APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815;
      sensitivity 85.7%, specificity 70.7%). CONCLUSIONS: ARFI, TE, and laboratory
      based fibrosis indices correlate with each other and reliably detect CFLD related
      liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in
      adults are lower than in alcoholic cirrhosis.

PMID- 22848733
TI  - Potential distribution of the Australian native Chloris truncata based on
      modelling both the successful and failed global introductions.
AB  - Our aim was to model the current and future potential global distribution of
      Chloris truncata (windmill grass) based on the plant's biology, soil requirements
      and colonisation success. The growth response of C. truncata to constant
      temperatures and soil moisture levels were measured and estimated respectively,
      to develop parameters for a CLIMEX bioclimatic model of potential distribution.
      The native distribution in eastern Australia and naturalised distribution in
      Western Australia was also used to inform the model. Associations with soil types
      were assessed within the suitable bioclimatic region in Australia. The global
      projection of the model was tested against the distribution of soil types and the
      known successful and failed global introductions. The verified model was then
      projected to future conditions due to climate change. Optimal temperature for
      plant development was 28 degrees C and the plant required 970 degree-days above a
      threshold of 10 degrees C. Early collection records indicate that the species is
      native to Queensland, New South Wales and Victoria. The plant has been introduced
      elsewhere in Australia and throughout the world as a wool contaminant and as a
      potential pasture species, but some of the recorded establishments have failed to
      persist. The CLIMEX model projected to the world reflected effectively both the
      successful and failed distributions. The inclusion of soil associations improved
      the explanation of the observed distribution in Australia, but did not improve
      the ability to determine the potential distribution elsewhere, due to lack of
      similarity of soil types between continents. The addition of a climate change
      projection showed decreased suitability for this species in Australia, but
      increased suitability for other parts of the world, including regions where the
      plant previously failed to establish.

PMID- 22848734
TI  - Discovery of novel dsRNA viral sequences by in silico cloning and implications
      for viral diversity, host range and evolution.
AB  - Genome sequence of viruses can contribute greatly to the study of viral
      evolution, diversity and the interaction between viruses and hosts. Traditional
      molecular cloning methods for obtaining RNA viral genomes are time-consuming and
      often difficult because many viruses occur in extremely low titers. DsRNA viruses
      in the families, Partitiviridae, Totiviridae, Endornaviridae, Chrysoviridae, and
      other related unclassified dsRNA viruses are generally associated with
      symptomless or persistent infections of their hosts. These characteristics
      indicate that samples or materials derived from eukaryotic organisms used to
      construct cDNA libraries and EST sequencing might carry these viruses, which were
      not easily detected by the researchers. Therefore, the EST databases may include
      numerous unknown viral sequences. In this study, we performed in silico cloning,
      a procedure for obtaining full or partial cDNA sequence of a gene by
      bioinformatics analysis, using known dsRNA viral sequences as queries to search
      against NCBI Expressed Sequence Tag (EST) database. From this analysis, we
      obtained 119 novel virus-like sequences related to members of the families,
      Endornaviridae, Chrysoviridae, Partitiviridae, and Totiviridae. Many of them were
      identified in cDNA libraries of eukaryotic lineages, which were not known to be
      hosts for these viruses. Furthermore, comprehensive phylogenetic analysis of
      these newly discovered virus-like sequences with known dsRNA viruses revealed
      that these dsRNA viruses may have co-evolved with respective host supergroups
      over a long evolutionary time while potential horizontal transmissions of viruses
      between different host supergroups also is possible. We also found that some of
      the plant partitiviruses may have originated from fungal viruses by horizontal
      transmissions. These findings extend our knowledge of the diversity and possible
      host range of dsRNA viruses and offer insight into the origin and evolution of
      relevant viruses with their hosts.

PMID- 22848735
TI  - A comprehensive evaluation of PCR primers to amplify the nifH gene of
      nitrogenase.
AB  - The nifH gene is the most widely sequenced marker gene used to identify nitrogen
      fixing Bacteria and Archaea. Numerous PCR primers have been designed to amplify
      nifH, but a comprehensive evaluation of nifH PCR primers has not been performed.
      We performed an in silico analysis of the specificity and coverage of 51
      universal and 35 group-specific nifH primers by using an aligned database of
      23,847 nifH sequences. We found that there are 15 universal nifH primers that
      target 90% or more of nitrogen fixers, but that there are also 23 nifH primers
      that target less than 50% of nifH sequences. The nifH primers we evaluated vary
      in their phylogenetic bias and their ability to recover sequences from commonly
      sampled environments. In addition, many of these primers will amplify genes that
      do not mediate nitrogen fixation, and thus it would be advisable for researchers
      to screen their sequencing results for the presence of non-target genes before
      analysis. Universal primers that performed well in silico were tested empirically
      with soil samples and with genomic DNA from a phylogenetically diverse set of
      nitrogen-fixing strains. This analysis will be of great utility to those engaged
      in molecular analysis of nifH genes from isolates and environmental samples.

PMID- 22848736
TI  - Analyzing multi-locus plant barcoding datasets with a composition vector method
      based on adjustable weighted distance.
AB  - BACKGROUND: The composition vector (CV) method has been proved to be a reliable
      and fast alignment-free method to analyze large COI barcoding data. In this
      study, we modify this method for analyzing multi-gene datasets for plant DNA
      barcoding. The modified method includes an adjustable-weighted algorithm for the
      vector distance according to the ratio in sequence length of the candidate genes
      for each pair of taxa. METHODOLOGY/PRINCIPAL FINDINGS: Three datasets, matK+rbcL
      dataset with 2,083 sequences, matK+rbcL dataset with 397 sequences and
      matK+rbcL+trnH-psbA dataset with 397 sequences, were tested. We showed that the
      success rates of grouping sequences at the genus/species level based on this
      modified CV approach are always higher than those based on the traditional K2P/NJ
      method. For the matK+rbcL datasets, the modified CV approach outperformed the K2P
      NJ approach by 7.9% in both the 2,083-sequence and 397-sequence datasets, and for
      the matK+rbcL+trnH-psbA dataset, the CV approach outperformed the traditional
      approach by 16.7%. CONCLUSIONS: We conclude that the modified CV approach is an
      efficient method for analyzing large multi-gene datasets for plant DNA barcoding.
      Source code, implemented in C++ and supported on MS Windows, is freely available
      for download at
      http://math.xtu.edu.cn/myphp/math/research/source/Barcode_source_codes.zip.

PMID- 22848737
TI  - A surgical model of permanent and transient middle cerebral artery stroke in the
      sheep.
AB  - BACKGROUND: Animal models are essential to study the pathophysiological changes
      associated with focal occlusive stroke and to investigate novel therapies.
      Currently used rodent models have yielded little clinical success, however large
      animal models may provide a more suitable alternative to improve clinical
      translation. We sought to develop a model of acute proximal middle cerebral
      artery (MCA) ischemic stroke in sheep, including both permanent occlusion and
      transient occlusion with reperfusion. MATERIALS AND METHODS: 18 adult male and
      female Merino sheep were randomly allocated to one of three groups (n = 6/gp): 1)
      sham surgery; 2) permanent proximal MCA occlusion (MCAO); or 3) temporary MCAO
      with aneurysm clip. All animals had invasive arterial blood pressure,
      intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel
      occlusion or sham surgery animals were killed by perfusion fixation. Brains were
      processed for histopathological examination and infarct area determination. 6
      further animals were randomized to either permanent (n = 3) or temporary MCAO (n
      = 3) and then had magnetic resonance imaging (MRI) at 4 h after MCAO. RESULTS:
      Evidence of ischemic injury in an MCA distribution was seen in all stroke
      animals. The ischemic lesion area was significantly larger after permanent
      (28.8%) compared with temporary MCAO (14.6%). Sham animals demonstrated no
      evidence of ischemic injury. There was a significant reduction in brain tissue
      oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins
      after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the
      permanent MCAO animals with a diffusion deficit involving the whole right MCA
      territory, whereas temporary MCAO animals demonstrated MRA evidence of flow
      within the right MCA and smaller predominantly cortical diffusion deficits.
      CONCLUSIONS: Proximal MCAO can be achieved in an ovine model of stroke via a
      surgical approach. Permanent occlusion creates larger infarct volumes, however
      aneurysm clip application allows for reperfusion.

PMID- 22848738
TI  - A novel HIV vaccine adjuvanted by IC31 induces robust and persistent humoral and
      cellular immunity.
AB  - The HIV vaccine strategy that, to date, generated immune protection consisted of
      a prime-boost regimen using a canarypox vector and an HIV envelope protein with
      alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV
      vaccine trials designed to generate antibody responses failed, we hypothesized
      that generation of T cell responses would result in improved protection. Thus, we
      tested the immunogenicity of a similar envelope-based vaccine using a mouse
      model, with two modifications: a clade C CN54gp140 HIV envelope protein was
      adjuvanted by the TLR9 agonist IC31(r), and the viral vector was the vaccinia
      strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31(r) facilitated
      immunoglobulin isotype switching, leading to the production of Env-specific
      IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted
      in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with
      IC31(r) and alum followed by NYVAC-CN54 boost resulted in the formation and
      persistence of central and effector memory populations in the spleen and an
      effector memory population in the gut. Our data suggest that this regimen is
      promising and could improve the protection rate by eliciting strong and long
      lasting humoral and cellular immune responses.

PMID- 22848739
TI  - Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC
      revealed by next generation sequencing: potential clinical implications.
AB  - Microdeletions at exon 19 are the most frequent genetic alterations affecting the
      Epidermal Growth Factor Receptor (EGFR) gene in non-small cell lung cancer
      (NSCLC) and they are strongly associated with response to treatment with tyrosine
      kinase inhibitors. A series of 116 NSCLC DNA samples investigated by Sanger
      Sequencing (SS), including 106 samples carrying exon 19 EGFR deletions and 10
      without deletions (control samples), were subjected to deep next generation
      sequencing (NGS). All samples with deletions at SS showed deletions with NGS. No
      deletions were seen in control cases. In 93 (88%) cases, deletions detected by
      NGS were exactly corresponding to those identified by SS. In 13 cases (12%) NGS
      resolved deletions not accurately characterized by SS. In 21 (20%) cases the NGS
      showed presence of complex (double/multiple) frameshift deletions producing a net
      in-frame change. In 5 of these cases the SS could not define the exact sequence
      of mutant alleles, in the other 16 cases the results obtained by SS were
      conventionally considered as deletions plus insertions. Different interpretative
      hypotheses for complex mutations are discussed. In 46 (43%) tumors deep NGS
      showed, for the first time to our knowledge, subpopulations of DNA molecules
      carrying EGFR deletions different from the main one. Each of these subpopulations
      accounted for 0.1% to 17% of the genomic DNA in the different tumors
      investigated. Our findings suggest that a region in exon 19 is highly unstable in
      a large proportion of patients carrying EGFR deletions. As a corollary to this
      study, NGS data were compared with those obtained by immunohistochemistry using
      the 6B6 anti-mutant EGFR antibody. The immunoreaction was E746-A750del specific.
      In conclusion, NGS analysis of EGFR exon 19 in NSCLCs allowed us to formulate a
      new interpretative hypothesis for complex mutations and revealed the presence of
      subpopulations of deletions with potential pathogenetic and clinical impact.

PMID- 22848740
TI  - FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own
      expression based on cellular AMP levels via a positive autoregulatory loop.
AB  - FOXO3 is a transcription factor involved in the regulation of multiple
      physiological processes including cell cycle arrest, apoptosis, oxidative stress
      response and energy metabolism. Although much is known about its post
      translational modification, the transcriptional regulation of FOXO3, as well as
      the cross-talk between transcription and post-translational events, is still
      poorly understood. In the present study, we show that FOXO3 is an immediate early
      glucocorticoid receptor (GR) target, whose transcription is even further enhanced
      by conditions that mimic metabolic stress. Induction of FOXO3 transcription by GR
      binding steroids was reversed by concomitant treatment with the GR antagonist RU
      486, but further enhanced by stimuli that activate the AMP-activated protein
      kinase (AMPK). Analysis of genomic DNA and chromatin immunoprecipitation, as well
      as luciferase reporter assays, revealed two functional glucocorticoid responsive
      elements within the FOXO3 promoter. Furthermore, we provide functional evidence
      for a phosphorylation switch that explains how glucocorticoids induce
      transcriptional activation of the gene but subsequently inactivate the
      corresponding protein by site-specific phosphorylation. Only when AMPK is
      stimulated, pre-existing FOXO3 becomes reverted toward an active form. Energy
      deprived conditions thus activate FOXO3 on two different levels, namely
      transcriptional and post-translational. In that way, FOXO3 acts as a metabolic
      stress sensor that coordinates expression of LKB1, the master upstream kinase
      involved in metabolic sensing, depending on the energy status of the cell.
      Additionally, we show that FOXO3 binds and activates its own promoter via a
      positive autoregulatory feedback loop. In conclusion, our data explain how
      catabolic glucocorticoid hormones and high intracellular AMP levels cooperate in
      inducing FOXO3 transcription and in activating the corresponding protein.

PMID- 22848742
TI  - Regulation of lean mass, bone mass, and exercise tolerance by the central
      melanocortin system.
AB  - Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant
      of body weight in mice and humans, where loss of function mutations lead to
      significant obesity. Humans with mutations in the MC4R experience an increase in
      lean mass. However, the simultaneous accrual of fat mass in such individuals may
      contribute to this effect via mechanical loading. We therefore examined the
      relationship of fat mass and lean mass in mice lacking the type-4 melanocortin
      receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body
      mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice
      possess more lean body mass than diet-induced obese (DIO) wild type mice with
      equivalent fat mass. To examine potential sources of the increased lean mass in
      MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters
      increase with age in MC4RKO mice, which likely contributes to increases in lean
      body mass. We functionally characterized the increased lean mass in MC4RKO mice
      by examining their capacity for treadmill running. MC4R deficiency results in a
      decrease in exercise performance. No changes in the ratio of oxidative to
      glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly
      reduced heart rate, which may underlie their impaired exercise performance. The
      reduced exercise capacity we report in the MC4RKO mouse has potential clinical
      ramifications, as efforts to control body weight in humans with melanocortin
      deficiency may be ineffective due to poor tolerance for physical activity.

PMID- 22848741
TI  - NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T
      cells.
AB  - Pattern recognition receptors (PRR), like Toll-like receptors (TLR) and NOD-like
      receptors (NLR), are involved in the detection of microbial infections and tissue
      damage by cells of the innate immune system. Recently, we and others have
      demonstrated that TLR2 can additionally function as a costimulatory receptor on
      CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is
      expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic
      ligand for NOD1, has a direct impact on both murine and human CD8 T cells,
      increasing proliferation and effector functions of cells activated via their T
      cell receptor (TCR). This effect is dependent on the adaptor molecule RIP2 and is
      associated with an increased activation of the NF-kappaB, JNK and p38 signaling
      pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with
      TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our
      results indicate that NOD1 might function as an alternative costimulatory
      receptor in CD8 T cells. Our study provides new insights into the function of NLR
      in T cells and extends to NOD1 the recent concept that PRR stimulation can
      directly control T cell functions.

PMID- 22848744
TI  - Protection against high-dose highly pathogenic mucosal SIV challenge at very low
      serum neutralizing titers of the antibody-like molecule CD4-IgG2.
AB  - Passive transfer studies using monoclonal or polyclonal antibodies in the macaque
      model have been valuable for determining conditions for antibody protection
      against immunodeficiency virus challenge. Most studies have employed hybrid
      simian/human immunodeficiency virus (SHIV) challenge in conjunction with
      neutralizing human monoclonal antibodies. Passive protection against SIV,
      particularly the pathogenic prototype virus SIVmac239, has been little studied
      because of the paucity of neutralizing antibodies to this virus. Here, we show
      that the antibody-like molecule CD4-IgG2 potently neutralizes SIVmac239 in vitro.
      When administered by an osmotic pump to maintain concentrations given the short
      half-life of CD4-IgG2 in macaques, the molecule provided sterilizing
      immunity/protection against high-dose mucosal viral challenge to a high
      proportion of animals (5/7 at a 200 mg dose CD4-IgG2 and 3/6 at a 20 mg dose) at
      serum concentrations below 1.5 ug/ml. The neutralizing titers of such sera were
      predicted to be very low and indeed sera at a 1:4 dilution produced no
      neutralization in a pseudovirus assay. Macaque anti-human CD4 titers did develop
      weakly at later time points in some animals but were not associated with the
      level of protection against viral challenge. The results show that, although
      SIVmac239 is considered a highly pathogenic virus for which vaccine-induced T
      cell responses in particular have provided limited benefit against high dose
      challenge, the antibody-like CD4-IgG2 molecule at surprisingly low serum
      concentration affords sterilizing immunity/protection to a majority of animals.

PMID- 22848743
TI  - Fluorescent in situ folding control for rapid optimization of cell-free membrane
      protein synthesis.
AB  - Cell-free synthesis is an open and powerful tool for high-yield protein
      production in small reaction volumes predestined for high-throughput structural
      and functional analysis. Membrane proteins require addition of detergents for
      solubilization, liposomes, or nanodiscs. Hence, the number of parameters to be
      tested is significantly higher than with soluble proteins. Optimization is
      commonly done with respect to protein yield, yet without knowledge of the protein
      folding status. This approach contains a large inherent risk of ending up with
      non-functional protein. We show that fluorophore formation in C-terminal fusions
      with green fluorescent protein (GFP) indicates the folding state of a membrane
      protein in situ, i.e. within the cell-free reaction mixture, as confirmed by
      circular dichroism (CD), proteoliposome reconstitution and functional assays.
      Quantification of protein yield and in-gel fluorescence intensity imply
      suitability of the method for membrane proteins of bacterial, protozoan, plant,
      and mammalian origin, representing vacuolar and plasma membrane localization, as
      well as intra- and extracellular positioning of the C-terminus. We conclude that
      GFP-fusions provide an extension to cell-free protein synthesis systems
      eliminating the need for experimental folding control and, thus, enabling rapid
      optimization towards membrane protein quality.

PMID- 22848745
TI  - Yersinia pestis intracellular parasitism of macrophages from hosts exhibiting
      high and low severity of plague.
AB  - BACKGROUND: Yersinia pestis causes severe disease in natural rodent hosts, but
      mild to inapparent disease in certain rodent predators such as dogs. Y. pestis
      initiates infection in susceptible hosts by parasitizing and multiplying
      intracellularly in local macrophages prior to systemic dissemination. Thus, we
      hypothesize that Y. pestis disease severity may depend on the degree to which
      intracellular Y. pestis overcomes the initial host macrophage imposed stress.
      METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, the progression of in
      vitro infection by Y. pestis KIM62053.1+ of mouse splenic and RAW264.7 tissue
      culture macrophages and dog peripheral blood-derived and DH82 tissue culture
      macrophages was studied using microscopy and various parameters of infection. The
      study showed that during the early stage of infection, intracellular Y. pestis
      assumed filamentous cellular morphology with multiple copies of the genome per
      bacterium in both mouse and dog macrophages. Later, in mouse macrophages, the
      infection elicited spacious vacuolar extension of Yersinia containing vacuoles
      (YCV), and the filamentous Y. pestis reverted to coccobacillary morphology with
      genomic equivalents approximately equaling colony forming units. In contrast, Y.
      pestis infected dog macrophages did not show noticeable extension of YCV, and
      intracellular Y. pestis retained the filamentous cellular morphology for the
      entire experiment in DH82 cells or were killed by blood-derived macrophages. In
      addition, during the later stage of infection, Y. pestis infected mouse
      macrophages exhibited cell lysis whereas dog macrophages did not.
      CONCLUSION/SIGNIFICANCE: Overall, these results support our hypothesis that Y.
      pestis in mouse macrophages can overcome the initial intracellular stress
      necessary for subsequent systemic infection. However, in dogs, failure of Y.
      pestis to overcome macrophage imposed stress may result in mild or in apparent
      disease in dogs.

PMID- 22848746
TI  - Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and
      exhibit exaggerated responses to Toll-like receptor ligands.
AB  - The leading cause of pregnancy-associated mortality and morbidity is pre
      eclampsia (PE). Although information regarding the etiology of this disease is
      scant, its pathophysiology is characterized by abnormal placentation, endothelial
      dysfunction as well as an exaggerated inflammatory response. Clinical evidence
      also indicates that the abundance of many immune cells at the feto-maternal
      interface and in the circulation of PE patients is abnormal, when compared with
      normal pregnant (NP) controls. In addition, the phenotype and function of some of
      these cells is altered. To further characterize the systemic effects of PE on
      circulating cells, we analyzed monocytic subpopulations in NP and PE patients by
      flow cytometry. We found that non-classical CD14(low)CD16(+) monocytes are
      significantly increased in women with PE and they display irregular expression of
      several chemokine receptors and antigen presentation molecules. The most striking
      phenotypic difference among the cell surface molecules was the marked
      upregulation of TLR4 expression, where both CD14(high)CD16(+) and
      CD14(low)CD16(+) monocytes demonstrated higher levels than their NP counterparts.
      Stimulation of PE monocytes with TLR ligands resulted in profound secretion of
      various cytokines in comparison with NP controls. These data suggest that PE
      monocytes are hyper-responsive to TLR ligands and this may contribute to
      exacerbation of the disease.

PMID- 22848747
TI  - Visual versus automated evaluation of chest computed tomography for the presence
      of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Incidental CT findings may provide an opportunity for early detection
      of chronic obstructive pulmonary disease (COPD), which may prove important in CT
      based lung cancer screening setting. We aimed to determine the diagnostic
      performance of human observers to visually evaluate COPD presence on CT images,
      in comparison to automated evaluation using quantitative CT measures. METHODS:
      This study was approved by the Dutch Ministry of Health and the institutional
      review board. All participants provided written informed consent. We studied 266
      heavy smokers enrolled in a lung cancer screening trial. All subjects underwent
      volumetric inspiratory and expiratory chest computed tomography (CT). Pulmonary
      function testing was used as the reference standard for COPD. We evaluated the
      diagnostic performance of eight observers and one automated model based on
      quantitative CT measures. RESULTS: The prevalence of COPD in the study population
      was 44% (118/266), of whom 62% (73/118) had mild disease. The diagnostic accuracy
      was 74.1% in the automated evaluation, and ranged between 58.3% and 74.3% for the
      visual evaluation of CT images. The positive predictive value was 74.3% in the
      automated evaluation, and ranged between 52.9% and 74.7% for the visual
      evaluation. Interobserver variation was substantial, even within the subgroup of
      experienced observers. Agreement within observers yielded kappa values between
      0.28 and 0.68, regardless of the level of expertise. The agreement between the
      observers and the automated CT model showed kappa values of 0.12-0.35.
      CONCLUSIONS: Visual evaluation of COPD presence on chest CT images provides at
      best modest accuracy and is associated with substantial interobserver variation.
      Automated evaluation of COPD subjects using quantitative CT measures appears
      superior to visual evaluation by human observers.

PMID- 22848748
TI  - The association between cold spells and pediatric outpatient visits for asthma in
      Shanghai, China.
AB  - BACKGROUND: Asthma is a serious global health problem. However, few studies have
      investigated the relationship between cold spells and pediatric outpatient visits
      for asthma. OBJECTIVE: To examine the association between cold spells and
      pediatric outpatient visits for asthma in Shanghai, China. METHODS: We collected
      daily data on pediatric outpatient visits for asthma, mean temperature, relative
      humidity, and ozone from Shanghai between 1 January 2007 and 31 December 2009. We
      defined cold spells as four or more consecutive days with temperature below the
      5(th) percentile of temperature during 2007-2009. We used a Poisson regression
      model to examine the impact of temperature on pediatric outpatient visits for
      asthma in cold seasons during 2007 and 2009. We examined the effect of cold
      spells on asthma compared with non-cold spell days. RESULTS: There was a
      significant relationship between cold temperatures and pediatric outpatient
      visits for asthma. The cold effects on children's asthma were observed at
      different lags. The lower the temperatures, the higher the risk for asthma
      attacks among children. CONCLUSION: Cold temperatures, particularly cold spells,
      significantly increase the risk of pediatric outpatient visits for asthma. The
      findings suggest that asthma children need to be better protected from cold
      effects in winter.

PMID- 22848749
TI  - Fluorine-19 magnetic resonance angiography of the mouse.
AB  - PURPOSE: To implement and characterize a fluorine-19 ((19)F) magnetic resonance
      imaging (MRI) technique and to test the hypothesis that the (19)F MRI signal in
      steady state after intravenous injection of a perfluoro-15-crown-5 ether (PCE)
      emulsion may be exploited for angiography in a pre-clinical in vivo animal study.
      MATERIALS AND METHODS: In vitro at 9.4T, the detection limit of the PCE emulsion
      at a scan time of 10 min/slice was determined, after which the T(1) and T(2) of
      PCE in venous blood were measured. Permission from the local animal use committee
      was obtained for all animal experiments. 12 ul/g of PCE emulsion was
      intravenously injected in 11 mice. Gradient echo (1)H and (19)F images were
      obtained at identical anatomical levels. Signal-to-noise (SNR) and contrast-to
      noise (CNR) ratios were determined for 33 vessels in both the (19)F and (1)H
      images, which was followed by vessel tracking to determine the vessel conspicuity
      for both modalities. RESULTS: In vitro, the detection limit was ~400 uM, while
      the (19)F T(1) and T(2) were 1350+/-40 and 25+/-2 ms. The (19)F MR angiograms
      selectively visualized the vasculature (and the liver parenchyma over time) while
      precisely coregistering with the (1)H images. Due to the lower SNR of (19)F
      compared to (1)H (17+/-8 vs. 83+/-49, p<0.001), the (19)F CNR was also lower at
      15+/-8 vs. 52+/-35 (p<0.001). Vessel tracking demonstrated a significantly higher
      vessel sharpness in the (19)F images (66+/-11 vs. 56+/-12, p = 0.002).
      CONCLUSION: (19)F magnetic resonance angiography of intravenously administered
      perfluorocarbon emulsions is feasible for a selective and exclusive visualization
      of the vasculature in vivo.

PMID- 22848750
TI  - Flowering time modulation by a vacuolar SNARE via FLOWERING LOCUS C in
      Arabidopsis thaliana.
AB  - The transition of plant growth from vegetative to reproductive phases is one of
      the most important and dramatic events during the plant life cycle. In
      Arabidopsis thaliana, flowering promotion involves at least four genetically
      defined regulatory pathways, including the photoperiod-dependent, vernalization
      dependent, gibberellin-dependent, and autonomous promotion pathways. Among these
      regulatory pathways, the vernalization-dependent and autonomous pathways are
      integrated by the expression of FLOWERING LOCUS C (FLC), a negative regulator of
      flowering; however, the upstream regulation of this locus has not been fully
      understood. The SYP22 gene encodes a vacuolar SNARE protein that acts in vacuolar
      and endocytic trafficking pathways. Loss of SYP22 function was reported to lead
      to late flowering in A. thaliana plants, but the mechanism has remained
      completely unknown. In this study, we demonstrated that the late flowering
      phenotype of syp22 was due to elevated expression of FLC caused by impairment of
      the autonomous pathway. In addition, we investigated the DOC1/BIG pathway, which
      is also suggested to regulate vacuolar/endosomal trafficking. We found that
      elevated levels of FLC transcripts accumulated in the doc1-1 mutant, and that
      syp22 phenotypes were exaggerated with a double syp22 doc1-1 mutation. We further
      demonstrated that the elevated expression of FLC was suppressed by ara6-1, a
      mutation in the gene encoding plant-unique Rab GTPase involved in endosomal
      trafficking. Our results indicated that vacuolar and/or endocytic trafficking is
      involved in the FLC regulation of flowering time in A. thaliana.

PMID- 22848752
TI  - Single-cell pulsed-field gel electrophoresis to detect the early stage of DNA
      fragmentation in human sperm nuclei.
AB  - Single-cell pulsed-field gel electrophoresis (SCPFGE) with dual electrode pairs
      was developed to detect the early stage of DNA fragmentation in human sperm. The
      motile sperm were purified by the commonly used density-gradient centrifugation
      technique and subsequent swim-up. The sperm were embedded in a thin film of
      agarose containing bovine trypsin (20 ug/mL) and were then lysed. Prior to
      SCPFGE, proteolysis of DNA-binding components, such as protamine and the nuclear
      matrix was essential to separate the long chain fibers from the fibrous and
      granular fragments derived from a single nucleus. The overall electrophoretic
      profiles elucidated the course of DNA fragmentation. A few large fibrous
      fragments were observed at the beginning of the process, however, as the
      fragmentation advanced, the long chain fibers decreased and shortened, and,
      conversely, the granular fragments increased until finally almost all the DNA was
      shredded. Although the ejaculate contained sperm with heterogeneous stages, the
      purified motile sperm exhibited several dozens of uniformly elongated fibers
      arising from the tangled DNA at the origin, whereas a part of these fibers gave
      rise to fibrous fragments beyond the tip of the elongated fibers, and their
      numbers and sizes varied among the sperm. Conventional intra-cytoplasmic sperm
      injection (ICSI) usually depends on intra-operative light microscopic observation
      to select a sperm for injection. The present results revealed that sperm motility
      could not give full assurance of DNA integrity. SCPFGE is likely to serve an
      important role in the preoperative differential diagnosis to determine the
      competence of the sperm population provided for injection.

PMID- 22848751
TI  - Characterization of Danio rerio Mn2+-dependent ADP-ribose/CDP-alcohol
      diphosphatase, the structural prototype of the ADPRibase-Mn-like protein family.
AB  - The ADPRibase-Mn-like protein family, that belongs to the metallo-dependent
      phosphatase superfamily, has different functional and structural prototypes. The
      functional one is the Mn(2+)-dependent ADP-ribose/CDP-alcohol diphosphatase from
      Rattus norvegicus, which is essentially inactive with Mg(2+) and active with low
      micromolar Mn(2+) in the hydrolysis of the phosphoanhydride linkages of ADP
      ribose, CDP-alcohols and cyclic ADP-ribose (cADPR) in order of decreasing
      efficiency. The structural prototype of the family is a Danio rerio protein with
      a known crystallographic structure but functionally uncharacterized. To estimate
      the structure-function correlation with the same protein, the activities of
      zebrafish ADPRibase-Mn were studied. Differences between zebrafish and rat
      enzymes are highlighted. The former showed a complex activity dependence on
      Mn(2+), significant (~25%) Mg(2+)-dependent activity, but was almost inactive on
      cADPR (150-fold less efficient than the rat counterpart). The low cADPR hydrolase
      activity agreed with the zebrafish genome lacking genes coding for proteins with
      significant homology with cADPR-forming enzymes. Substrate-docking to zebrafish
      wild-type protein, and characterization of the ADPRibase-Mn H97A mutant pointed
      to a role of His-97 in catalysis by orientation, and to a bidentate water
      bridging the dinuclear metal center as the potential nucleophile. Finally, three
      structural elements that delimit the active site entrance in the zebrafish
      protein were identified as unique to the ADPRibase-Mn-like family within the
      metallo-dependent phosphatase superfamily.

PMID- 22848753
TI  - Age-specific sex-related differences in infections: a statistical analysis of
      national surveillance data in Japan.
AB  - BACKGROUND: To prevent and control infectious diseases, it is important to
      understand how sex and age influence morbidity rates, but consistent clear
      descriptions of differences in the reported incidence of infectious diseases in
      terms of sex and age are sparse. METHODS AND FINDINGS: Data from the Japanese
      surveillance system for infectious diseases from 2000 to 2009 were used in the
      analysis of seven viral and four bacterial infectious diseases with relatively
      large impact on the Japanese community. The male-to-female morbidity (MFM) ratios
      in different age groups were estimated to compare incidence rates of symptomatic
      reported infection between the sexes at different ages. MFM ratios were >1 for
      five viral infections out of seven in childhood, i.e. male children were more
      frequently reported as infected than females with pharyngoconjunctival fever,
      herpangina, hand-foot-and-mouth disease, mumps, and varicella. More males were
      also reported to be infected with erythema infectiosum and exanthema subitum, but
      only in children 1 year of age. By contrast, in adulthood the MFM ratios
      decreased to <1 for all of the viral infections above except varicella, i.e.
      adult women were more frequently reported to be infected than men. Sex- and age
      related differences in reported morbidity were also documented for bacterial
      infections. Reported morbidity for enterohemorrhagic Escherichia coli infection
      was higher in adult females and females were reportedly more infected with
      mycoplasma pneumonia than males in all age groups up to 70 years. CONCLUSIONS:
      Sex-related differences in reported morbidity for viral and bacterial infections
      were documented among different age groups. Changes in MFM ratios with age may
      reflect differences between the sexes in underlying development processes,
      including those affecting the immune, endocrine, and reproductive systems, or
      differences in reporting rates.

PMID- 22848754
TI  - The unique karyotype of Henochilus wheatlandii, a critically endangered fish
      living in a fast-developing region in Minas Gerais State, Brazil.
AB  - Henochilus wheatlandii, the only species of this genus, is critically endangered
      and was considered extinct for over a century. The rediscovery of this fish in
      1996 made it possible to study its phylogenetic relationships with other species
      in the subfamily Bryconinae. The aim of this study was to characterise the
      karyotype of H. wheatlandii. Standard staining, C-positive heterochromatin and
      nucleolar organiser region (NOR) banding, chromomycin A(3) staining, and
      fluorescent in situ hybridisation (FISH) using 5S rDNA and 18S rDNA probes were
      conducted on nineteen specimens collected in the Santo Antonio River, a sub-basin
      of the Doce River in Ferros municipality, Minas Gerais State, Brazil. Henochilus
      wheatlandii shared the same diploid number and chromosome morphology as other
      species of Bryconinae. However, its heterochromatin distribution patterns, NOR
      localisation, and FISH patterns revealed a cytogenetic profile unique among
      Neotropical Bryconinae, emphasizing the evolutionary uniqueness of this
      threatened species.

PMID- 22848755
TI  - Connexin45 is expressed in vascular smooth muscle but its function remains
      elusive.
AB  - Connexins (Cx) form gap junctions and allow the coordination of cellular
      behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and
      specifically Cx40 serves important functions in endothelial cells. In contrast,
      expression and physiological functions of Cx45 is unclear although its expression
      has been suggested in vascular smooth muscle (VSM). Therefore, we studied
      expression and function of Cx45 in vessels using different mice models allowing
      to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was
      achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin
      promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced
      green fluorescence protein (EGFP) in these mice. Conduction of vasomotor
      responses was studied in cremasteric arterioles using intravital microscopy and
      arterial pressure was measured telemetrically. Cx45 is transcriptionally
      expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient
      mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre).
      Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice
      carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations
      evoked by the endothelium-dependent agonist acetylcholine were not different
      between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed
      Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated
      endothelium-independent constrictions (K(+)) and dilations (adenosine) declined
      similarly with distance in both genotypes indicating an intact VSM conduction
      pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not
      different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during
      day or night. We conclude that Cx45 is physiologically expressed in VSM, but not
      in EC in murine arterioles. However, Cx45 is dispensable for the conduction of
      vasomotor responses along these arterioles. Possibly, other Cx functionally
      replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion
      does not seem to alter arterial pressure in freely moving mice.

PMID- 22848756
TI  - Application of flow cytometry to determine differential redistribution of
      cytochrome c and Smac/DIABLO from mitochondria during cell death signaling.
AB  - Mitochondrially mediated apoptosis is characterized by redistribution of proteins
      from mitochondria to cytoplasm following permeabilization of the outer
      mitochondrial membrane. We applied flow cytometry to quantify simultaneously the
      redistribution of two apoptogenic proteins, cytochrome c (cyt c) and Smac/DIABLO
      (Smac). Mammalian cells were treated with digitonin that selectively
      permeabilizes the plasma membrane. Following fixation, treated cells were infused
      successively with primary and secondary antibodies (the latter fluorescently
      tagged) enabling independent detection of cyt c and Smac. Digitonin-treated cells
      that retain cyt c or Smac in mitochondria generate strong fluorescence signals in
      flow cytometry. Cells in which cyt c or Smac have transited the outer
      mitochondrial membrane show greatly reduced fluorescence because the proteins are
      lost from the digitonin-permeabilized cells. Quantitative flow cytometry revealed
      that in 143B TK(-) cells treated with staurosporine, cyt c and Smac exit
      mitochondria asymmetrically, with cyt c redistribution preceding that of Smac.
      However, in HeLa cells likewise treated, cyt c and Smac exit mitochondria
      concurrently. Under other conditions of apoptotic induction, for example, 143B
      TK(-) cells treated with MT-21 (an apoptotic inducer that binds to the
      mitochondrial adenine nucleotide transporter), redistribution of Smac precedes
      that of cyt c. The various patterns of redistribution of these proteins were
      confirmed by immunocytochemical analysis and confocal microscopy. We conclude
      that flow cytometry can be employed effectively to quantify simultaneously the
      redistribution of cyt c and Smac from mitochondria to the cytosol. Moreover,
      differential redistribution of cyt c and Smac occurs under various conditions,
      thereby reflecting constraints on availability of these proteins to exit
      mitochondria after permeabilization of the outer membrane.

PMID- 22848757
TI  - Reduced neural synchrony in patients with restless legs syndrome during a visual
      oddball task.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor neurological disorder
      characterized by an irresistible urge to move the legs. It has been reported that
      RLS patients show cognitive deficits, presumably due to hyperactivity causing
      loss of attention, or malfunctions in the frontal region resulting from sleep
      deprivation. However, the mechanism underlying cognitive deficits in RLS patients
      is mostly unknown. As an effort to clarifying this, we investigated the
      differences in neural activity and phase synchrony between healthy controls and
      RLS patients during cognitive task performances. METHODOLOGY/PRINCIPAL FINDINGS:
      Seventeen female drug-naive RLS patients were enrolled in the study, and an age
      matched group of thirteen healthy female volunteers served as controls.
      Multichannel event-related potentials (ERPs) were recorded from RLS patients and
      normal controls while performing a visual oddball task. In addition to
      conventional analyses of ERP waveforms and spectra, interregional gamma-band
      phase synchrony (GBPS) was investigated to observe the differences in
      interregional neural synchronies between normal and RLS patient groups. Strong
      GBPS was observed primarily between anterior and posterior regions along the
      midline for both groups. Along with significant reduction and delay of P300 ERP
      and induced gamma-band activity (GBA), the GBPS was considerably decreased in RLS
      patients compared to normal subjects, especially at frontal region. CONCLUSIONS:
      Overall, our results support that cognitive dysfunction in RLS patients is
      associated with reduced interregional neural synchrony as well as alterations in
      local neural activity.

PMID- 22848758
TI  - XMRV induces cell migration, cytokine expression and tumor angiogenesis: are
      22Rv1 cells a suitable prostate cancer model?
AB  - 22Rv1 is a common prostate cancer cell line used in xenograft mouse experiments
      as well as in vitro cell culture assays to study aspects of prostate cancer
      tumorigenesis. Recently, this cell line was shown to harbor multiple copies of a
      gammaretrovirus, called XMRV, integrated in its genome. While the original
      prostate cancer xenograft CWR22 is free of any retrovirus, subsequently generated
      cell lines 22Rv1 and CWR-R1, carry this virus and additionally shed infectious
      gammaretroviral particles in their supernatant. Although XMRV most likely was
      generated by recombination events in cell culture this virus has been
      demonstrated to infect human cells in vitro and 22Rv1 as well as CWR-R1 cells are
      now considered biosafety 2 reagents. Here, we demonstrate that 22Rv1 cells with
      reduced retroviral transcription show reduced tumor angiogenesis and increased
      necrosis of the primary tumor derived from xenografted cells in scid mice when
      compared to the parental cell line. The presence of XMRV transcripts
      significantly increases secretion of osteopontin (OPN), CXCL14, IL13 and TIMP2 in
      22Rv1 cells. Furthermore, these data are supported by in vitro cell invasion and
      differentiation assays. Collectively, our data suggest that the presence of XMRV
      transcripts at least partially contributes to 22Rv1 characteristics observed in
      vitro and in vivo with regard to migration, invasion and tumor angiogenesis. We
      propose that data received with 22Rv1 cells or equivalent cells carrying
      xenotropic gammaretroviruses should be carefully controlled including other
      prostate cancer cell lines tested for viral sequences.

PMID- 22848759
TI  - The neural bases of social intention understanding: the role of interaction
      goals.
AB  - Decoding others' intentions is a crucial aspect of social cognition. Neuroimaging
      studies suggest that inferring immediate goals engages the neural system for
      action understanding (i.e. mirror system), while the decoding of long-term
      intentions requires the system subserving the attribution of mental states (i.e.
      mentalizing). A controversial issue, stimulated by recent inconsistent results,
      concerns whether the two systems are concurrently vs. exclusively involved in
      intention understanding. This issue is particularly relevant in the case of
      social interactions, whose processing has been mostly, but not uncontroversially,
      associated with the mentalizing system. We tested the alternative hypothesis that
      the relative contribution of the two systems in intention understanding may also
      depend on the shared goal of interacting agents. To this purpose, 27 participants
      observed social interactions differing in their cooperative vs. affective shared
      goal during functional-Magnetic-Resonance-Imaging. The processing of both types
      of interactions activated the right temporo-parietal junction involved in
      mentalizing on action goals. Additionally, whole-brain and regions-of-interest
      analyses showed that the action understanding system (inferior prefrontal
      parietal cortex) was more strongly activated by cooperative interactions, while
      the mentalizing-proper system (medial prefrontal cortex) was more strongly
      engaged by affective interactions. These differences were modulated by individual
      differences in empathizing. Both systems can thus be involved in understanding
      social intentions, with a relative weighting depending on the specific shared
      goal of the interaction.

PMID- 22848760
TI  - Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter
      in mitochondrial respiration and oxidative phosphorylation. In genomic DNA,
      NAD(+) also represents the sole substrate for the nuclear repair enzyme, poly(ADP
      ribose) polymerase (PARP) and the sirtuin family of NAD-dependent histone
      deacetylases. Age associated increases in oxidative nuclear damage have been
      associated with PARP-mediated NAD(+) depletion and loss of SIRT1 activity in
      rodents. In this study, we further investigated whether these same associations
      were present in aging human tissue. Human pelvic skin samples were obtained from
      consenting patients aged between 15-77 and newborn babies (0-1 year old) (n = 49)
      previously scheduled for an unrelated surgical procedure. DNA damage correlated
      strongly with age in both males (p = 0.029; r = 0.490) and females (p = 0.003; r
      = 0.600) whereas lipid oxidation (MDA) levels increased with age in males (p =
      0.004; r = 0.623) but not females (p = 0.3734; r = 0.200). PARP activity
      significantly increased with age in males (p<0.0001; r = 0.768) and inversely
      correlated with tissue NAD(+) levels (p = 0.0003; r = -0.639). These associations
      were less evident in females. A strong negative correlation was observed between
      NAD(+) levels and age in both males (p = 0.001; r = -0.706) and females (p =
      0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p
      = 0.007; r = -0.612) but not in females. Strong positive correlations were also
      observed between lipid peroxidation and DNA damage (p<0.0001; r = 0.4962), and
      PARP activity and NAD(+) levels (p = 0.0213; r = 0.5241) in post pubescent males.
      This study provides quantitative evidence in support of the hypothesis that
      hyperactivation of PARP due to an accumulation of oxidative damage to DNA during
      aging may be responsible for increased NAD(+) catabolism in human tissue. The
      resulting NAD(+) depletion may play a major role in the aging process, by
      limiting energy production, DNA repair and genomic signalling.

PMID- 22848761
TI  - Diagnostic potential of the NMDA receptor peptide assay for acute ischemic
      stroke.
AB  - BACKGROUND: The acute assessment of patients with suspected ischemic stroke
      remains challenging. The use of brain biomarker assays may improve the early
      diagnosis of ischemic stroke. The main goal of the study was to evaluate whether
      the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate
      (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics
      and persons with vascular risk factors/healthy controls. A possible correlation
      between biomarker values and lesion sizes was investigated as the secondary
      objective. METHODS AND FINDINGS: A total of 192 patients with suspected stroke
      who presented within 72 h of symptom onset were prospectively enrolled. The final
      diagnosis was determined based on clinical observations and radiological
      findings. Additionally gender- and age-matched healthy controls (n = 52) and
      persons with controlled vascular risk factors (n = 48) were recruited to compare
      NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP)
      ELISA for NR2 peptide within 30 min and results for different groups compared
      using univariate and multivariate statistical analyses. There was a clinical
      diagnosis of IS in 101 of 192 (53%) and non-stroke in 91 (47%) subjects. The non
      stroke group included presented with acute stroke symptoms who had no stroke (n =
      71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in
      patients with IS that peaked at 12 h following symptom onset. When the biomarker
      cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92% and a
      specificity of 96% to detect IS. A moderate correlation (r(s) = 0.73) between NR2
      peptide values and acute ischemic cortical lesions (<200 mL) was found.
      CONCLUSIONS: This study suggests that the NR2 peptide may be a brain specific
      biomarker to diagnose acute IS and may allow the differentiation of IS from
      stroke mimics and controls. Additional larger scale clinical validation studies
      are required.

PMID- 22848762
TI  - Seroprevalence and risk factors for Coxiella burnetii (Q fever) seropositivity in
      dairy goat farmers' households in The Netherlands, 2009-2010.
AB  - Community Q fever epidemics occurred in The Netherlands in 2007-2009, with dairy
      goat and dairy sheep farms as the implicated source. The aim of the study was to
      determine the seroprevalence and risk factors for seropositivity in dairy goat
      farmers and their household members living or working on these farms. Sera of 268
      people living or working on 111 dairy goat farms were tested for Coxiella
      burnetii IgG and IgM antibodies using immunofluorescence assay. Seroprevalences
      in farmers, spouses and children (12-17 years) were 73.5%, 66.7%, and 57.1%,
      respectively. Risk factors for seropositivity were: performing three or more
      daily goat-related tasks, farm location in the two southern provinces of the
      country, proximity to bulk milk-positive farms, distance from the nearest stable
      to residence of 10 meters or less, presence of cats and multiple goat breeds in
      the stable, covering stable air spaces and staff not wearing farm boots. Goat
      farmers have a high risk to acquire this occupational infection. Clinicians
      should consider Q fever in this population presenting with compatible symptoms to
      allow timely diagnosis and treatment to prevent severe sequelae. Based on the
      risk factors identified, strengthening general biosecurity measures is
      recommended such as consistently wearing boots and protective clothing by farm
      staff to avoid indirect transmission and avoiding access of companion animals in
      the goat stable. Furthermore, it provides an evidence base for continuation of
      the current vaccination policy for small ruminants, preventing spread from
      contaminated farms to other farms in the vicinity. Finally, vaccination of
      seronegative farmers and household members could be considered.

PMID- 22848763
TI  - Drosophila heat shock response requires the JNK pathway and phosphorylation of
      mixed lineage kinase at a conserved serine-proline motif.
AB  - Defining context specific requirements for proteins and pathways is a major
      challenge in the study of signal transduction. For example, the stress-activated
      protein kinase (SAPK) pathways are comprised of families of closely related
      transducers that are activated in a variety of tissues and contexts during
      development and organismal homeostasis. Consequently, redundant and pleiotropic
      effects have hampered a complete understanding of the individual contributions of
      transducers in distinct contexts. Here, we report on the function of a context
      specific regulatory phosphorylation site, PXSP, in the Drosophila mixed lineage
      kinase protein, Slpr, a mitogen-activated protein kinase kinase kinase (MAP3K) in
      the Jun Kinase (JNK) pathway. Genetic analysis of the function of non
      phosphorylatable (PXAP) and phosphomimetic mutant (PXEP) Slpr transgenes in
      several distinct contexts revealed minimal effects in JNK-dependent tissue
      closure processes but differential requirements in heat stress response. In
      particular, PXAP expression resulted in sensitivity of adults to sustained heat
      shock, like p38 and JNK pathway mutants. In contrast, PXEP overexpression
      conferred some resistance. Indeed, phosphorylation of the PXSP motif is enriched
      under heat shock conditions and requires in part, the p38 kinases for the
      enrichment. These data suggest that coordination of signaling between p38 and
      Slpr serves to maintain JNK signaling during heat stress. In sum, we demonstrate
      a novel role for JNK signaling in the heat shock response in flies and identify a
      posttranslational modification on Slpr, at a conserved site among MAP3K mixed
      lineage kinase family members, which bolsters stress resistance with negligible
      effects on JNK-dependent developmental processes.

PMID- 22848764
TI  - Research questions and priorities for tuberculosis: a survey of published
      systematic reviews and meta-analyses.
AB  - BACKGROUND: Systematic reviews are increasingly informing policies in
      tuberculosis (TB) care and control. They may also be a source of questions for
      future research. As part of the process of developing the International Roadmap
      for TB Research, we did a systematic review of published systematic reviews on
      TB, to identify research priorities that are most frequently suggested in
      reviews. METHODOLOGY/PRINCIPAL FINDINGS: We searched EMBASE, MEDLINE, Web of
      Science, and the Cochrane Library for systematic reviews and meta-analyses on any
      aspect of TB published between 2005 and 2010. One reviewer extracted data and a
      second reviewer independently extracted data from a random subset of included
      studies. In total, 137 systematic reviews, with 141 research questions, were
      included in this review. We used the UK Health Research Classification System
      (HRCS) to help us classify the research questions and priorities. The three most
      common research topics were in the area of detection, screening and diagnosis of
      TB (32.6%), development and evaluation of treatments and therapeutic
      interventions (23.4%), and TB aetiology and risk factors (19.9%). The research
      priorities determined were mainly focused on the discovery and evaluation of
      bacteriological TB tests and drug-resistant TB tests and immunological tests.
      Other important topics of future research were genetic susceptibility linked to
      TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments
      for TB, drug-resistant TB and HIV/TB were also frequently proposed research
      topics. CONCLUSIONS: Systematic reviews are a good source of key research
      priorities. Findings from our survey have informed the development of the
      International Roadmap for TB Research by the TB Research Movement.

PMID- 22848765
TI  - Partnering parasites: evidence of synergism between heavy Schistosoma haematobium
      and Plasmodium species infections in Kenyan children.
AB  - BACKGROUND: Residents of resource-poor tropical countries carry heavy burdens of
      concurrent parasitic infections, leading to high rates of morbidity and
      mortality. This study was undertaken to help identify the social and
      environmental determinants of multiple parasite infection in one such community.
      METHODOLOGY/PRINCIPAL FINDINGS: Residents of Kingwede, Kenya aged 8 years and
      older were tested for presence and intensity of S. haematobium and Plasmodium
      spp. infections in a cross-sectional, household-based, community survey. Using
      General Estimating Equation (GEE) models, social and environmental determinants
      associated with patterns of co-infection were identified, with age being one of
      the most important factors. Children had 9.3 times the odds of co-infection
      compared to adults (95%CI=5.3-16.3). Even after controlling for age, socio
      economic position, and other correlates of co-infection, intense concomitant
      infections with the two parasites were found to cluster in a subset of
      individuals: the odds of heavy vs. light S. haematobium infection increased with
      increasing Plasmodium infection intensity suggesting the importance of unmeasured
      biological factors in determining intensity of co-infection.
      CONCLUSIONS/SIGNIFICANCE: Children in this community are more likely to be
      infected with multiple parasites than are adults and should therefore be targeted
      for prevention and control interventions. More importantly, heavy infections with
      multiple parasite species appear to cluster within a subset of individuals.
      Further studies focusing on these most vulnerable people are warranted.

PMID- 22848766
TI  - Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini:
      a randomized, single-blinded dose-comparison trial.
AB  - BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance
      in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control
      but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren
      were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis
      viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of
      infections were determined by a rigorous diagnostic effort (3 stool specimens,
      each examined with triplicate Kato-Katz) before and 28-30 days after treatment.
      Ninety children with full baseline data were randomized to receive PZQ: the 40
      mg/kg standard single dose (n = 45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg,
      4 hours apart; n = 45). Adverse events were assessed at 3 and 24 hours
      posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi
      and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were
      75.0% (95% confidence interval (CI): 56.6-88.5%) and 80.8% (95% CI: 60.6-93.4%)
      for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60). O. viverrini cure rates
      were significantly different at 71.4% (95% CI: 53.4-84.4%) and 96.6% (95% CI: not
      defined), respectively (P = 0.009). Egg reduction rates (ERRs) against O.
      viverrini were very high for both doses (>99%), but slightly lower for S. mekongi
      at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort.
      O. viverrini cure rates would have been overestimated and no statistical
      difference between doses found if efficacy was based on a minimum sampling effort
      (single Kato-Katz before and after treatment). Adverse events were common (96%),
      mainly mild with no significant differences between the two treatment groups.
      CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more
      efficacious than 40 mg/kg against O. viverrini but not against S. mekongi
      infections, while ERRs were similar for both doses. TRIAL REGISTRATION:
      Controlled-Trials.com ISRCTN57714676.

PMID- 22848767
TI  - In-silico investigation of antitrypanosomal phytochemicals from Nigerian
      medicinal plants.
AB  - BACKGROUND: Human African trypanosomiasis (HAT), a parasitic protozoal disease,
      is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging
      disease and currently threatens millions of people in sub-Saharan Africa. Many
      affected people live in remote areas with limited access to health services and,
      therefore, rely on traditional herbal medicines for treatment. METHODS: A
      molecular docking study has been carried out on phytochemical agents that have
      been previously isolated and characterized from Nigerian medicinal plants, either
      known to be used ethnopharmacologically to treat parasitic infections or known to
      have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species
      of medicinal plants were investigated using in-silico molecular docking with
      validated Trypanosoma brucei protein targets that were available from the Protein
      Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1),
      dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B
      (TbCatB), heat shock protein 90 (TbHSP90), sterol 14alpha-demethylase (TbCYP51),
      nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2
      deoxyribosyltransferase (TbNDRT), UDP-galactose 4' epimerase (TbUDPGE), and
      ornithine decarboxylase (TbODC). RESULTS: This study revealed that triterpenoid
      and steroid ligands were largely selective for sterol 14alpha-demethylase;
      anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine
      reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred
      docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids
      showed notable docking energies with UDP-galactose 4' epimerase (TbUDPGE).
      Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended
      to be promiscuous docking agents, giving strong docking energies with most
      proteins. CONCLUSIONS: This in-silico molecular docking study has identified
      potential biomolecular targets of phytochemical components of antitrypanosomal
      plants and has determined which phytochemical classes and structural manifolds
      likely target trypanosomal enzymes. The results could provide the framework for
      synthetic modification of bioactive phytochemicals, de novo synthesis of
      structural motifs, and lead to further phytochemical investigations.

PMID- 22848768
TI  - Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and
      immunomodulatory effects over IFN-alpha in HTLV-1-associated myelopathy.
AB  - BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of
      randomized double-blind controlled clinical trials. Moderate yet similar clinical
      benefit has been demonstrated for IFN-alpha and high-dose ascorbic acid (AA)
      monotherapy in a large open clinical trial. However, there is a lack of in vivo
      and in vitro studies exploring and comparing the effects of high-dose AA and IFN
      alpha treatment in the context of HAM/TSP. Therefore, we performed the first
      comparative analysis of the ex vivo and in vitro molecular and cellular
      mechanisms of action of IFN-alpha and high-dose AA in HAM/TSP. PRINCIPAL
      FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17
      cytokines, we demonstrate that high-dose AA displays differential and superior
      antiproliferative and immunomodulatory effects over IFN-alpha in HAM/TSP PBMCs ex
      vivo. In addition, high-dose AA, but not IFN-alpha, induced cell death in both
      HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data
      combined with pathway analysis of MT-2 cells revealed AA-induced regulation of
      genes associated with cell death, including miR-155. Since miR-155 has recently
      been demonstrated to up-regulate IFN-gamma, this microRNA might represent a novel
      therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis,
      another neuroinflammatory disease. On the other hand, IFN-alpha selectively up
      regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN
      alpha, high-dose AA treatment has superior ex vivo and in vitro cell death
      inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects.
      Differential pathway activation by both drugs opens up avenues for targeted
      treatment in specific patient subsets.

PMID- 22848769
TI  - Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey
      model of second stage human African trypanosomiasis.
AB  - Novel drugs to treat human African trypanosomiasis (HAT) are still urgently
      needed despite the recent addition of nifurtimox-eflornithine combination therapy
      (NECT) to WHO Model Lists of Essential Medicines against second stage HAT, where
      parasites have invaded the central nervous system (CNS). The pharmacology of a
      potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino)
      phenyl]-furan-2-yl}-nicotinamidine (DB844), was evaluated in a vervet monkey
      model of second stage HAT, following promising results in mice. DB844 was
      administered orally to vervet monkeys, beginning 28 days post infection (DPI)
      with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted
      to the active metabolite 6-[5-(4-phenylamidinophenyl)-furanyl-2-yl]-nicotinamide
      (DB820), exhibiting plasma C(max) values of 430 and 190 nM for DB844 and DB820,
      respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood
      trypanosome counts was observed within 24 h of the third dose and, at the end of
      treatment evaluation performed four days post the last drug dose, trypanosomes
      were not detected in the blood or cerebrospinal fluid of any monkey. However,
      some animals relapsed during the 300 days of post treatment monitoring, resulting
      in a cure rate of 3/8 (37.5%) and 3/7 (42.9%) for the 5 mg/kg*10 days and the 6
      mg/kg*14 days dose regimens respectively. These DB844 efficacy data were an
      improvement compared with pentamidine and pafuramidine both of which were
      previously shown to be non-curative in this model of CNS stage HAT. These data
      show that synthesis of novel diamidines with improved activity against CNS-stage
      HAT was possible.

PMID- 22848770
TI  - Adenovirus delivered short hairpin RNA targeting a conserved site in the 5' non
      translated region inhibits all four serotypes of dengue viruses.
AB  - BACKGROUND: Dengue is a mosquito-borne viral disease caused by four closely
      related serotypes of Dengue viruses (DENVs). This disease whose symptoms range
      from mild fever to potentially fatal haemorrhagic fever and hypovolemic shock,
      threatens nearly half the global population. There is neither a preventive
      vaccine nor an effective antiviral therapy against dengue disease. The difference
      between severe and mild disease appears to be dependent on the viral load. Early
      diagnosis may enable timely therapeutic intervention to blunt disease severity by
      reducing the viral load. Harnessing the therapeutic potential of RNA interference
      (RNAi) to attenuate DENV replication may offer one approach to dengue therapy.
      METHODOLOGY/PRINCIPAL FINDINGS: We screened the non-translated regions (NTRs) of
      the RNA genomes of representative members of the four DENV serotypes for putative
      siRNA targets mapping to known transcription/translation regulatory elements. We
      identified a target site in the 5' NTR that maps to the 5' upstream AUG region, a
      highly conserved cis-acting element essential for viral replication. We used a
      replication-defective human adenovirus type 5 (AdV5) vector to deliver a short
      hairpin RNA (shRNA) targeting this site into cells. We show that this shRNA
      matures to the cognate siRNA and is able to inhibit effectively antigen
      secretion, viral RNA replication and infectious virus production by all four DENV
      serotypes. CONCLUSION/SIGNIFICANCE: The data demonstrate the feasibility of using
      AdV5-mediated delivery of shRNAs targeting conserved sites in the viral genome to
      achieve inhibition of all four DENV serotypes. This paves the way towards
      exploration of RNAi as a possible therapeutic strategy to curtail DENV infection.

PMID- 22848771
TI  - Leishmania major infection in humanized mice induces systemic infection and
      provokes a nonprotective human immune response.
AB  - BACKGROUND: Leishmania (L.) species are the causative agent of leishmaniasis. Due
      to the lack of efficient vaccine candidates, drug therapies are the only option
      to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic
      interventions show high toxicity in addition to an increased risk of
      dissemination of drug-resistant parasites. An appropriate laboratory animal based
      model is still missing which allows testing of new drug strategies in the context
      of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice
      were infected subcutaneously with stationary phase promastigote L. major into the
      footpad. The human immune response against the pathogen and the parasite host
      interactions were analyzed. In addition we proved the versatility of this new
      model to conduct drug research studies by the inclusion of orally given
      Miltefosine. We show that inflammatory human macrophages get infected with
      Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific
      human-derived T cell response is initiated. However, the human immune system is
      not able to prevent systemic infection. Thus, we treated the mice with
      Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in
      a reduction of the parasite load in distinct organs. Comparable to some
      Miltefosine treated patients, humanized mice developed severe side effects, which
      are not detectable in the classical murine model of experimental leishmaniasis.
      CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major
      infection in humanized mice, characterizes the disease development, the induction
      of human adaptive and innate immune response including cytokine production and
      the efficiency of Miltefosine treatment in these animals. In summary, humanized
      mice might be beneficial for future preclinical chemotherapeutic studies in
      systemic (visceral) leishmaniasis allowing the investigation of human immune
      response, side effects of the drug due to cytokine production of activated humane
      immune cells and the efficiency of the treatment to eliminate also not
      replicating ("hiding") parasites.

PMID- 22848772
TI  - Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC)
      oral cholera vaccine in pregnancy.
AB  - INTRODUCTION: Mass vaccinations are a main strategy in the deployment of oral
      cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the
      absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine.
      Balancing this concern is the known higher risk of cholera and of complications
      of pregnancy should cholera occur in these women, as well as the lack of expected
      adverse events from a killed oral bacterial vaccine. METHODOLOGY/PRINCIPAL
      FINDINGS: From January to February 2009, a mass rBS-WC vaccination campaign of
      persons over two years of age was conducted in an urban and a rural area
      (population 51,151) in Zanzibar. Pregnant women were advised not to participate
      in the campaign. More than nine months after the last dose of the vaccine was
      administered, we visited all women between 15 and 50 years of age living in the
      study area. The outcome of pregnancies that were inadvertently exposed to at
      least one oral cholera vaccine dose and those that were not exposed was
      evaluated. 13,736 (94%) of the target women in the study site were interviewed.
      1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when
      foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151
      mothers had not been vaccinated; the remaining 196 (17%) mothers had received at
      least one dose of the oral cholera vaccine. There were no statistically
      significant differences in the odds ratios for birth outcomes among the exposed
      and unexposed pregnancies. CONCLUSIONS/SIGNIFICANCE: We found no statistically
      significant evidence of a harmful effect of gestational exposure to the rBS-WC
      vaccine. These findings, along with the absence of a rational basis for expecting
      a risk from this killed oral bacterial vaccine, are reassuring but the study had
      insufficient power to detect infrequent events. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00709410.

PMID- 22848773
TI  - Maternal geohelminth infections are associated with an increased susceptibility
      to geohelminth infection in children: a case-control study.
AB  - BACKGROUND: Children of mothers infected with soil-transmitted helminths (STH)
      may have an increased susceptibility to STH infection. METHODS AND FINDINGS: We
      did a case-control study nested in a birth cohort in Ecuador. Data from 1,004
      children aged 7 months to 3 years were analyzed. Cases were defined as children
      with Ascaris lumbricoides and/or Trichuris trichiura, controls without. Exposure
      was defined as maternal infection with A. lumbricoides and/or T. trichiura,
      detected during the third trimester of pregnancy. The analysis was restricted to
      households with a documented infection to control for infection risk. Children of
      mothers with STH infections had a greater risk of infection compared to children
      of uninfected mothers (adjusted OR 2.61, 95% CI: 1.88-3.63, p<0.001). This effect
      was particularly strong in children of mothers with both STH infections (adjusted
      OR: 5.91, 95% CI: 3.55-9.81, p<0.001). Newborns of infected mothers had greater
      levels of plasma IL-10 than those of uninfected mothers (p=0.033), and there was
      evidence that cord blood IL-10 was increased among newborns who became infected
      later in childhood (p=0.060). CONCLUSION: Our data suggest that maternal STH
      infections increase susceptibility to infection during early childhood, an effect
      that was associated with elevated IL-10 in cord plasma.

PMID- 22848774
TI  - Wolbachia induces density-dependent inhibition to dengue virus in mosquito cells.
AB  - Wolbachia is a maternal transmitted endosymbiotic bacterium that is estimated to
      infect up to 65% of insect species. The ability of Wolbachia to both induce viral
      interference and spread into mosquito vector population makes it possible to
      develop Wolbachia as a biological control agent for dengue control. While
      Wolbachia induces resistance to dengue virus in the transinfected Aedes aegypti
      mosquitoes, a similar effect was not observed in Aedes albopictus, which
      naturally carries Wolbachia infection but still serves as a dengue vector. In
      order to understand the mechanism of this lack of Wolbachia-mediated viral
      interference, we used both Ae. albopictus cell line (Aa23) and mosquitoes to
      characterize the impact of Wolbachia on dengue infection. A serial of sub-lethal
      doses of antibiotic treatment was used to partially remove Wolbachia in Aa23
      cells and generate cell cultures with Wolbachia at different densities. We show
      that there is a strong negative linear correlation between the genome copy of
      Wolbachia and dengue virus with a dengue infection completely removed when
      Wolbacha density reaches a certain level. We then compared Wolbachia density
      between transinfected Ae. aegypti and naturally infected Ae. albopictus. The
      results show that Wolbachia density in midgut, fatbody and salivary gland of Ae.
      albopictus is 80-, 18-, and 24-fold less than that of Ae. aegypti, respectively.
      We provide evidence that Wolbachia density in somatic tissues of Ae. albopictus
      is too low to induce resistance to dengue virus. Our results will aid in
      understanding the mechanism of Wolbachia-mediated pathogen interference and
      developing novel methods to block disease transmission by mosquitoes carrying
      native Wolbachia infections.

PMID- 22848775
TI  - Previous multiple abdominal surgeries: a valid contraindication to abdominal free
      flap breast reconstruction?
AB  - PRESENTED IN PART AT THE FOLLOWING ACADEMIC MEETINGS: 57th Meeting of the Italian
      Society of Plastic, Reconstructive and Aesthetic Surgery, September 24-27, 2008,
      Naples, Italy.45th Congress of the European Society for Surgical Research (ESSR),
      June 9-12, 2010, Geneva, Switzerland.British Association of Plastic
      Reconstructive and Aesthetic Surgeons Summer Scientific Meeting, June 30-July 2,
      2010, Sheffield Hallam University, Sheffield, UK. BACKGROUND: Patients with
      previous multiple abdominal surgeries are often denied abdominal free flap breast
      reconstruction because of concerns about flap viability and abdominal wall
      integrity. We therefore studied their flap and donor site outcomes and compared
      them to patients with no previous abdominal surgery to find out whether this is a
      valid contraindication to the use of abdominal tissue. PATIENTS AND METHODS:
      Twenty patients with multiple previous abdominal operations who underwent
      abdominal free flap breast reconstruction by a single surgeon (C.M.M., 2000-2009)
      were identified and retrospectively compared with a cohort of similar patients
      without previous abdominal surgery (sequential allocation control group, n = 20).
      RESULTS: The index and control groups were comparable in age, body mass index,
      comorbidities, previous chemotherapy, and RT exposure. The index patients had a
      mean age of 54 years (r, 42-63) and an average body mass index of 27.5 kg/m(2)
      (r, 22-38). The main previous surgeries were Caesarean sections (19),
      hysterectomies (8), and cholecystectomies (6). They underwent immediate (n = 9)
      or delayed (n = 11) reconstructions either unilaterally (n = 18) or bilaterally
      (n = 2) and comprising 9 muscle-sparing free transverse rectus abdominis muscle
      and 13 deep inferior epigastric perforator flaps. All flaps were successful, and
      there were no significant differences in flap and donor site outcomes between the
      2 groups after an average follow up of 26 months (r, 10-36). CONCLUSION: Multiple
      previous abdominal surgeries did not predispose to increased flap or donor site
      morbidity. On the basis of our experience, we have proposed some recommendations
      for successful abdominal free flap breast reconstruction in patients with
      previous multiple scars. Careful preoperative planning and the use of some
      intraoperative adaptations can allow abdominal free flap breast reconstruction to
      be reliably undertaken in such patients.

PMID- 22848776
TI  - CASE REPORT Use of a Hydroconductive Dressing to Treat a Traumatic Avulsive
      Injury of the Face.
AB  - INTRODUCTION AND OBJECTIVE: Traumatic avulsive injuries present complex
      therapeutic decisions. Radical and repeated debridement of all foreign material,
      necrotic tissue, bacteria, and deleterious chemicals followed by control of the
      bacterial bioburden and wound closure has been the gold standard. However, when
      such injuries occur in the face, the treatment requires modification. Specialized
      structures, nerves, and a maximum amount of tissue must be preserved. Topical
      antimicrobials may lead to dessication and further injury to tissue. Therefore,
      alternative treatments must be considered. Recently, a hydroconductive dressing
      has been demonstrated to decrease edema by removing excess exudate, to remove
      debris and necrotic tissue, and to decrease bacteria and deleterious cytokines in
      wounds. METHODS: Regular dressings were done between 1 and 3 days by dedicated
      personnel, using a hydroconductive dressing. Following an initial conservative
      debridement and reconstruction while attempting to preserve as much of the normal
      structure as possible, the wounds were dressed with a hydroconductive dressing.
      RESULTS: Using only selective conservative debridement following bony
      reconstruction and repeated hydroconductive dressing changes, this severe injury
      healed with preservation of the important facial features. No further extensive
      surgical procedures were required. On discharge, the patient was able to function
      well with a reasonably good aesthetic result. She was subsequently lost to follow
      up. CONCLUSION: This case report demonstrates that a hydroconductive dressing can
      be useful for traumatic avulsive injuries.

PMID- 22848777
TI  - Accidental inclusions following blast injury in esthetical zones: ablation by a
      hydrosurgery system.
AB  - In case of blast injuries, traumatic tattoos can result from accidental
      inclusions of intradermal pigmented particles. To avoid these tattoos, especially
      in esthetical areas like the head and neck region and the hands, the primary goal
      in our treatment is to remove all particles and foreign bodies. Superficial
      foreign bodies can easily be removed by brushes or dermabrasion. Deeper lesions
      are a challenge for plastic surgeons, because they are not so easily removed.
      Ablation by a water jet surgical tool, the Versajet-system (Smith & Nephew Inc,
      Andover, MA), enables the removal of nearly all particles and foreign bodies,
      which sustained a blast injury of the face or the hands. Aim of this paper is to
      describe the method of using this hydrosurgery system in blast injuries in
      esthetical zones and its advantages by presenting cases of two patients of us.

PMID- 22848778
TI  - A malignant neoplasm imitating a subcutaneous cyst.

PMID- 22848779
TI  - Investigation of effects and mechanisms of total flavonoids of Astragalus and
      calycosin on human erythroleukemia cells.
AB  - Flavonoids are found in most parts of plants and have been shown to have multiple
      biological activities such as anticancer, anti-inflammation, antibacteria,
      antivirus, and immune-stimulation. Existing data showed that the total flavonoids
      of Astragalus (TFA) can provide biological system with resistance to injury and
      can possess antimutagenic, atherosclerotic inhibition, and other biological
      effects. This study investigated the effects of TFA and calycosin (a compound
      isolated from TFA), on apoptosis induction, and cell cycle of human
      erythroleukemia cell line K562 by an array of techniques, including proliferation
      (MTT), PI staining, Annexin V/PI double staining, and RT-PCR. The experimental
      data showed that TFA and calycosin could inhibit the proliferation of K562 cells.
      The 50% inhibiting concentrations of TFA and calycosin were 98.63 MUg/mL and
      130.32 MUg/mL, respectively. However, TFA and calycosin could not induce
      apoptosis in K562 cells, but could increase the number of the cells in the
      G(0)/G(1) phase. The level of cyclin D1 mRNA in K562 cells decreased after the
      treatment with TFA and calycosin. This study provides new insights into the
      functional mechanism of total flavonoids of Astragalus and calycosin on human
      erythroleukemia cells.

PMID- 22848780
TI  - Bicarbonate plays a critical role in the generation of cytotoxicity during SIN-1
      decomposition in culture medium.
AB  - 3-Morpholinosydnonimine (SIN-1) is used as a donor of peroxynitrite (ONOO(-)) in
      various studies. We demonstrated, however, that, the cell-culture medium remains
      cytotoxic to PC12 cells even after almost complete SIN-1 decomposition,
      suggesting that reaction product(s) in the medium, rather than ONOO(-), exert
      cytotoxic effects. Here, we clarified that significant cytotoxicity persists
      after SIN-1 decomposes in bicarbonate, a component of the culture medium, but not
      in NaOH. Cytotoxic SIN-1-decomposed bicarbonate, which lacks both oxidizing and
      nitrosating activities, degrades to innocuous state over time. The extent of SIN
      1 cytotoxicity, irrespective of its fresh or decomposed state, appears to depend
      on the total number of initial SIN-1 molecules per cell, rather than its
      concentration, and involves oxidative/nitrosative stress-related cell damage.
      These results suggest that, despite its low abundance, the bicarbonate-dependent
      cytotoxic substance that accumulates in the medium during SIN-1 breakdown is the
      cytotoxic entity of SIN-1.

PMID- 22848781
TI  - Low-frequency fatigue as an indicator of eccentric exercise-induced muscle
      injury: the role of vitamin E.
AB  - This study investigates whether vitamin E can attenuate eccentric exercise
      induced soleus muscle injury as indicated by the amelioration of in situ
      isometric force decline following a low-frequency fatigue protocol (stimulation
      at 4 Hz for 5 min) and the ability of the muscle to recover 3 min after the
      termination of the fatigue protocol. Adult male Wistar rats were divided into
      vitamin E-supplemented or placebo-supplemented groups studied at rest,
      immediately post-exercise or 48 h post-exercise. Daily dl-alpha-tocopheryl
      acetate intraperitoneal injections of 100 mg/kg body mass for 5 consecutive days
      prior to exercise doubled its plasma levels. Fatigue index and recovery index
      expressed as a percentage of the initial tension. FI at 0 h post- and 48 h post
      exercise respectively was 88% +/- 4.2% and 89% +/- 6.8% in the vitamin E groups
      versus 76% +/- 3% and 80% +/- 11% in the placebo groups. RI was 99% +/- 3.4% and
      100% +/- 6% in the vitamin E groups versus 82% +/- 3.1% and 84% +/- 5.9% in the
      placebo groups. Complementally to the traditionally recorded maximal force, low
      frequency fatigue measures may be beneficial for assessing injury-induced
      decrease in muscle functionality.

PMID- 22848782
TI  - The role of hydrogen peroxide in environmental adaptation of oral microbial
      communities.
AB  - Oral streptococci are able to produce growth-inhibiting amounts of hydrogen
      peroxide (H(2)O(2)) as byproduct of aerobic metabolism. Several recent studies
      showed that the produced H(2)O(2) is not a simple byproduct of metabolism but
      functions in several aspects of oral bacterial biofilm ecology. First, the
      release of DNA from cells is closely associated to the production of H(2)O(2) in
      Streptococcus sanguinis and Streptococcus gordonii. Extracellular DNA is crucial
      for biofilm development and stabilization and can also serve as source for
      horizontal gene transfer between oral streptococci. Second, due to the growth
      inhibiting nature of H(2)O(2), H(2)O(2) compatible species associate with the
      producers. H(2)O(2) production therefore might help in structuring the initial
      biofilm development. On the other hand, the oral environment harbors salivary
      peroxidases that are potent in H(2)O(2) scavenging. Therefore, the effects of
      biofilm intrinsic H(2)O(2) production might be locally confined. However, taking
      into account that 80% of initial oral biofilm constituents are streptococci, the
      influence of H(2)O(2) on biofilm development and environmental adaptation might
      be under appreciated in current research.

PMID- 22848784
TI  - Comment on "Cytokines and oxidative stress status following a handball game in
      elite male players".

PMID- 22848783
TI  - Oxidative stress and epilepsy: literature review.
AB  - BACKGROUNDS: The production of free radicals has a role in the regulation of
      biological function, cellular damage, and the pathogenesis of central nervous
      system conditions. Epilepsy is a highly prevalent serious brain disorder, and
      oxidative stress is regarded as a possible mechanism involved in epileptogenesis.
      Experimental studies suggest that oxidative stress is a contributing factor to
      the onset and evolution of epilepsy. OBJECTIVE: A review was conducted to
      investigate the link between oxidative stress and seizures, and oxidative stress
      and age as risk factors for epilepsy. The role of oxidative stress in seizure
      induction and propagation is also discussed. RESULTS/CONCLUSIONS: Oxidative
      stress and mitochondrial dysfunction are involved in neuronal death and seizures.
      There is evidence that suggests that antioxidant therapy may reduce lesions
      induced by oxidative free radicals in some animal seizure models. Studies have
      demonstrated that mitochondrial dysfunction is associated with chronic oxidative
      stress and may have an essential role in the epileptogenesis process; however,
      few studies have shown an established link between oxidative stress, seizures,
      and age.

PMID- 22848786
TI  - Is there diversity among UGT1A1 polymorphism in Japan?
AB  - AIM: To investigate into the diversity of UGT1A1 polymorphism across three
      different districts in Japan and highlight genetic differences among the
      population in Japan. METHODS: We enrolled 50 healthy volunteers from each of the
      Yamaguchi (western part of Japan), Kochi (southern part of Japan) and Akita
      (northern part of Japan) prefectures. Blood samples (7 mL) were collected from
      each participant and stored in EDTA for subsequent genotyping by fragment size
      analysis, direct sequencing and TaqMan assay of UGT1A1*28, UGT1A7*3/UGT1A9*22 and
      UGT1A1*93/UGT1A1*6/UGT1A1*27/UGT1A1*60/UGT1A7 (-57), respectively. RESULTS: The
      only statistically significant differences in allele polymorphisms among the
      group examined were for UGT1A1*6. The Akita population showed more UGT1A1*6
      heterozygosity (P = 0.0496). CONCLUSION: Our study revealed no regional diversity
      among UGT1A1, UGT1A7 or UGT1A9 polymorphisms in Japan.

PMID- 22848785
TI  - Interaction between overtraining and the interindividual variability may (not)
      trigger muscle oxidative stress and cardiomyocyte apoptosis in rats.
AB  - Severe endurance training (overtraining) may cause underperformance related to
      muscle oxidative stress and cardiomyocyte alterations. Currently, such
      relationship has not been empirically established. In this study, Wistar rats (n
      = 19) underwent eight weeks of daily exercise sessions followed by three
      overtraining weeks in which the daily frequency of exercise sessions increased.
      After the 11th training week, eight rats exhibited a reduction of 38% in
      performance (nonfunctional overreaching group (NFOR)), whereas eleven rats
      exhibited an increase of 18% in performance (functional overreaching group
      (FOR)). The red gastrocnemius of NFOR presented significantly lower citrate
      synthase activity compared to FOR, but similar to that of the control. The
      activity of mitochondrial complex IV in NFOR was lower than that of the control
      and FOR. This impaired mitochondrial adaptation in NFOR was associated with
      increased antioxidant enzyme activities and increased lipid peroxidation (in
      muscle and plasma) relative to FOR and control. Cardiomyocyte apoptosis was
      higher in NFOR. Plasma creatine kinase levels were unchanged. We observed that
      some rats that presented evidence of muscle oxidative stress are also subject to
      cardiomyocyte apoptosis under endurance overtraining. Blood lipid peroxides may
      be a suitable biomarker for muscle oxidative stress that is unrelated to severe
      muscle damage.

PMID- 22848787
TI  - Phenotypic traits of Phragmites australis clones are not related to ploidy level
      and distribution range.
AB  - BACKGROUND AND AIMS: Phragmites australis is a wetland grass with high genetic
      variability, augmented by its cosmopolitan distribution, clonal growth form and
      large variation in chromosome numbers. Different ploidy levels and ecotypes
      differ in morphology and ecophysiological traits, and may possess different
      levels of phenotypic variation. The aim of this study was to quantify the natural
      variation in ecophysiological characteristics of P. australis, and to explore
      whether differences in ecophysiological traits can be related to ploidy levels or
      to the geographic origin of the clones. METHODOLOGY: Fifteen clones of P.
      australis from Europe and Asia/Australia, representing five ploidy levels (4x,
      6x, 8x, 10x and 12x), were grown in a common garden design for 119 days. Plant
      growth and light-saturated rate of photosynthesis (P(max)), stomatal conductance
      (g(s)), water use efficiency (WUE) and concentrations of photosynthetic pigments
      and mineral ions in the leaves were measured. PRINCIPAL RESULTS: The growth of
      the plants and most ecophysiological parameters differed significantly between
      clones. The mean maximum shoot height varied from 0.9 to 1.86 m, P(max) from 9.7
      to 27 umol m(-2) s(-1), g(s) from 0.22 to 1.41 mol m(-2) s(-1) and WUE from 13 to
      47 umol mol(-1). The concentrations of chlorophylls did not vary significantly
      between clones, but the chlorophyll a/b ratio and the concentrations of total
      carotenoids did. The observed differences were not explained either by the ploidy
      level per se or by the geographic origin or phylogenetic relationships of the
      clones. CONCLUSIONS: Phylogeographic relationships in P. australis on a global
      scale do not mirror the environment where the adaptations have evolved, and high
      phenotypic variation among and within clones complicates comparative studies.
      Future studies aimed at explaining differences in plant behaviour between P.
      australis populations should be careful in the selection of target genotypes
      and/or populations, and should avoid generalizing their findings beyond the
      genotypes and/or populations studied.

PMID- 22848788
TI  - Beam-assisted large elongation of in situ formed Li2O nanowires.
AB  - As an important component of the solid electrolyte interface in lithium ion
      batteries and an effective blanket breeding material in fusion reactor, the
      mechanical property of Li(2)O is of great interest but is not well understood.
      Here we show that the polycrystalline Li(2)O nanowires were formed in situ by
      touching and pulling lithium hydroxide under electron beam (e-beam) illumination.
      The Li(2)O nanowires sustained an enhanced elongation (from 80% to 176%) under
      low dose e-beam irradiation near room temperature as compared with that (from 51%
      to 57%) without e-beam irradiation. The extremely high deformability could be
      understood by the fast Li(2)O diffusion under e-beam irradiation and tensile
      stress condition. The large elongation without e-beam irradiation implies that
      nano-structured Li(2)O is ductile near room temperature.

PMID- 22848789
TI  - Iron biofortification in rice by the introduction of multiple genes involved in
      iron nutrition.
AB  - To address the problem of iron-deficiency anemia, one of the most prevalent human
      micronutrient deficiencies globally, iron-biofortified rice was produced using
      three transgenic approaches: by enhancing iron storage in grains via expression
      of the iron storage protein ferritin using endosperm-specific promoters,
      enhancing iron translocation through overproduction of the natural metal chelator
      nicotianamine, and enhancing iron flux into the endosperm by means of iron(II)
      nicotianamine transporter OsYSL2 expression under the control of an endosperm
      specific promoter and sucrose transporter promoter. Our results indicate that the
      iron concentration in greenhouse-grown T(2) polished seeds was sixfold higher and
      that in paddy field-grown T(3) polished seeds was 4.4-fold higher than that in
      non-transgenic seeds, with no defect in yield. Moreover, the transgenic seeds
      accumulated zinc up to 1.6-times in the field. Our results demonstrate that
      introduction of multiple iron homeostasis genes is more effective for iron
      biofortification than the single introduction of individual genes.

PMID- 22848790
TI  - A synthetic small molecule for rapid induction of multiple pluripotency genes in
      mouse embryonic fibroblasts.
AB  - Cellular reprogramming involves profound alterations in genome-wide gene
      expression that is precisely controlled by a hypothetical epigenetic code. Small
      molecules have been shown to artificially induce epigenetic modifications in a
      sequence independent manner. Recently, we showed that specific DNA binding
      hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin
      modifying histone deacetylase inhibitors like SAHA to epigenetically activate
      certain pluripotent genes in mouse fibroblasts. In our steadfast progress to
      improve the efficiency of SAHA-PIPs, we identified a novel compound termed, delta
      that could dramatically induce the endogenous expression of Oct-3/4 and Nanog.
      Genome-wide gene analysis suggests that in just 24 h and at nM concentration,
      delta induced multiple pluripotency-associated genes including Rex1 and Cdh1 by
      more than ten-fold. delta treated MEFs also rapidly overcame the rate-limiting
      step of epithelial transition in cellular reprogramming by switching "[Formula:
      see text]" the complex transcriptional gene network.

PMID- 22848792
TI  - Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis
      Patients Colonised with Pseudomonas aeruginosa Using Multiple Combination
      Bactericidal Testing.
AB  - Early infection is a recognised complication after lung transplantation in
      patients with cystic fibrosis (CF). Our centre uses multiple combination
      bactericidal testing (MCBT) when determining appropriate peritransplant
      prophylactic regimens. To evaluate our strategy, we compared the incidence of
      posttransplant infection in patients whose peritransplant antimicrobial regimens
      were determined using MCBT versus standard sensitivity testing. Patients with CF
      who were infected with Pseudomonas aeruginosa and underwent lung transplantations
      between 2000 and 2010 were included. Data was collected from clinical records and
      our microbiology database. Microorganisms cultured were mapped against antibiotic
      resistance, method of sensitivity testing, and antibiotics administered
      peritransplant. 129 patients were identified (mean age 28, male : female, 63 :
      66). Fifty patients (38.8%) had antibiotics determined by MCBT. Two patients in
      the MCBT group developed septicaemia, 13 in the conventional group (P <= 0.05, 2
      tailed Fisher's test). Sepsis was attributable to P. aeruginosa in one patient
      from the MCBT group and seven patients in the conventional group (P = 0.15). P.
      aeruginosa was recovered from the posttransplant pleural fluid of one patient who
      received MCBT-guided prophylaxis, six patients in the conventional group (P =
      0.25). Patients given antibiotics based on MCBT had significantly lower rates of
      septicaemia and lower rates of empyema.

PMID- 22848791
TI  - Hippocampal protection in mice with an attenuated inflammatory monocyte response
      to acute CNS picornavirus infection.
AB  - Neuronal injury during acute viral infection of the brain is associated with the
      development of persistent cognitive deficits and seizures in humans. In C57BL/6
      mice acutely infected with the Theiler's murine encephalomyelitis virus,
      hippocampal CA1 neurons are injured by a rapid innate immune response, resulting
      in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice
      exhibit essentially complete hippocampal and memory preservation. Analysis of
      brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated
      inflammatory monocyte response as compared to B6 mice. Bone marrow
      transplantation experiments isolated the attenuation to the SJL immune system.
      Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts
      converted these mice to a hippocampal damage phenotype and induced a cognitive
      deficit marked by failure to recognize a novel object. These findings show that
      inflammatory monocytes are the critical cellular mediator of hippocampal injury
      during acute picornavirus infection of the brain.

PMID- 22848793
TI  - Pilot study of the delivery of microcollimated pars plana external beam radiation
      in porcine eyes: 270-day analysis.
AB  - Objective. To determine the dose response and toxicity threshold of micro
      collimated X-rays delivered to porcine maculae by a stereotactic radiosurgical
      system after 270 days. Methods. Twelve eyes of six Yucatan mini-swine were
      randomized to receive up to 90 Gy to the retina, using an office-based trans-pars
      plana delivery system. To determine the safety profile of this radiation
      delivery, ophthalmic examination, fundus photography, fluorescein angiography
      (FA), and spectral domain optical coherence tomography (SD-OCT) were obtained at
      multiple time points up to 270 days post treatment. Results. No abnormalities
      were noted on external examination. Cataracts were noted in 4 of 12 eyes. Dose
      and time-dependent changes were noted on fundus examination, FA, ICG and SD-OCT.
      No significant abnormalities were seen in the control, 16 Gy or 24 Gy groups
      using any modality. Histopathology revealed a dose response effect with no
      discernable lesions in the 16 Gy group. Conclusion. The X-ray delivery system
      precisely targets the porcine retina in vivo with little effect on surrounding
      structures. No ophthalmic or intracranial adverse effects were noted at
      clinically relevant doses at 270 days following radiation delivery.

PMID- 22848794
TI  - In Vitro Activities of Kissorphin, a Novel Hexapeptide KiSS-1 Derivative, in
      Neuronal Cells.
AB  - The primary products of the metastasis-suppressor KiSS-1 gene are the kisspeptin
      (KP) peptides that stimulate gonadotrophin-releasing-hormone (GnRH) release via
      GPR-54 receptor activation. Recent studies have suggested that the KP-10 peptide
      also activates neuropeptide FF (NPFF) receptors. The aim of the current study was
      to determine the activities of the KiSS-1 derivative kissorphin (KSO), which
      contains the first six amino acids of the KP-10 peptide, is C-terminally
      amidated, and shares amino acid similarities with the biologically active NPFF 3
      8 sequence. The KSO peptide inhibited forskolin-stimulated cyclic adenosine
      monophosphate (cAMP) production in ND7/23 neuroblastoma cells via an action that
      could be inhibited by the NPFF receptor antagonist RF9. Release of GnRH by LA-N-1
      neuroblastoma cells was not altered by the KSO peptide. In ND7/23 neuroblastoma
      cells, the KSO peptide was able to reduce forskolin neuroprotection against
      H(2)O(2) toxicity. The KSO peptide was also able to prevent prostaglandin E2
      induced apoptosis in rat cortical neurons. The NPFF receptor antagonist RF9 could
      inhibit these actions of the KSO peptide in oxidative stress and apoptosis
      models. In conclusion, the kissorphin peptide, comprising the amino acid sequence
      Tyr-Asn-Trp-Asn-Ser-Phe-NH(2), has NPFF-like biological activity without showing
      any GnRH releasing activity and inhibits forskolin-activated cAMP release.

PMID- 22848796
TI  - Convenient and scalable synthesis of fmoc-protected Peptide nucleic Acid
      backbone.
AB  - The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a
      scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then
      alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an
      Fmoc group. The synthesis was performed starting with 50 g of Boc anhydride to
      give 31 g of product in 32% overall yield. The Fmoc-protected PNA backbone is a
      key intermediate in the synthesis of nucleobase-modified PNA monomers. Thus,
      improved access to this molecule is anticipated to facilitate future
      investigations into the chemical properties and applications of nucleobase
      modified PNA.

PMID- 22848795
TI  - Ways of coping and biomarkers of an increased atherothrombotic cardiovascular
      disease risk in elderly individuals.
AB  - Objective. To investigate the relationship between coping and atherothrombotic
      biomarkers of an increased cardiovascular disease (CVD) risk in the elderly.
      Methods. We studied 136 elderly caregiving and noncaregiving men and women who
      completed the Ways of Coping Checklist to assess problem-focused coping, seeking
      social support (SSS), blamed self, wishful thinking, and avoidance coping. They
      had circulating levels of 12 biomarkers measured. We also probed for potential
      mediator and moderator variables (chronic stress, affect, health behavior,
      autonomic activity) for the relation between coping and biomarkers. Results.
      After controlling for demographic and CVD risk factors, greater use of SSS was
      associated with elevated levels of serum amyloid A (P = 0.001), C-reactive
      protein (CRP) (P = 0.002), vascular cellular adhesion molecule (VCAM)-1 (P =
      0.021), and D-dimer (P = 0.032). There were several moderator effects. For
      instance, greater use of SSS was associated with elevated VCAM-1 (P < 0.001) and
      CRP (P = 0.001) levels in subjects with low levels of perceived social support
      and positive affect, respectively. The other coping styles were not significantly
      associated with any biomarker. Conclusions. Greater use of SSS might compromise
      cardiovascular health through atherothrombotic mechanisms, including elevated
      inflammation (i.e., serum amyloid A, CRP, VCAM-1) and coagulation (i.e., D-dimer)
      activity. Moderating variables need to be considered in this relationship.

PMID- 22848797
TI  - Barriers to physical activity in East harlem, new york.
AB  - Background. East Harlem is an epicenter of the intertwining epidemics of obesity
      and diabetes in New York. Physical activity is thought to prevent and control a
      number of chronic illnesses, including diabetes, both independently and through
      weight control. Using data from a survey collected on adult (age 18+) residents
      of East Harlem, this study evaluated whether perceptions of safety and community
      identified barriers were associated with lower levels of physical activity in a
      diverse sample. Methods. We surveyed 300 adults in a 2-census tract area of East
      Harlem and took measurements of height and weight. Physical activity was measured
      in two ways: respondents were classified as having met the weekly recommended
      target of 2.5 hours of moderate physical activity (walking) per week (or not) and
      reporting having engaged in at least one recreational physical activity (or not).
      Perceived barriers were assessed through five items developed by a community
      advisory board and perceptions of neighborhood safety were measured through an
      adapted 7-item scale. Two multivariate logistic regression models with perceived
      barriers and concerns about neighborhood safety were modeled separately as
      predictors of engaging in recommended levels of exercise and recreational
      physical activity, controlling for respondent weight and sociodemographic
      characteristics. Results. The most commonly reported perceived barriers to
      physical activity identified by nearly half of the sample were being too tired or
      having little energy followed by pain with exertion and lack of time.
      Multivariate regression found that individuals who endorsed a greater number of
      perceived barriers were less likely to report having met their weekly recommended
      levels of physical activity and less likely to engage in recreational physical
      activity controlling for covariates. Concerns about neighborhood safety, though
      prevalent, were not associated with physical activity levels. Conclusions.
      Although safety concerns were prevalent in this low-income, minority community,
      it was individual barriers that correlated with lower physical activity levels.

PMID- 22848798
TI  - Adult BMI Change and Risk of Colon Cancer in Postmenopausal Women.
AB  - Purpose. We recently reported an association of adult BMI change with colon
      cancer risk. Here, we sought to further explore this association with respect to
      postmenopausal HRT use in a larger study population. Methods. We included 1,457
      postmenopausal women participating in an ongoing population-based case-control
      study of colon cancer. Results. We confirmed a previously reported association of
      adulthood weight gain and increased risk of colon cancer: compared to those with
      <5 kg/m(2) change of BMI, women who reported moderate (5-10 kg/m(2)) and large
      (>10 kg/m(2)) BMI changes since their 20s had OR estimates of 1.54 (95% CI = 1.09
      2.19) and 1.45 (95% CI = 0.90-2.33), respectively (P for trend = 0.05).
      Stratified analyses showed that this association was limited to HRT nonusers: ORs
      were 1.77 (95% CI = 1.02-3.05) and 2.21 (95% CI = 1.09-4.45), respectively (P for
      trend = 0.03), for BMI changes occurring between the 20s decade and time of
      recruitment among non-users. Similar associations were observed for BMI changes
      since the 30s decade. There was no association among HRT users. Conclusion. Our
      results suggest early adulthood weight gain increases colon cancer risk in
      postmenopausal women who do not use HRT.

PMID- 22848799
TI  - A systematic review of clinical diagnostic systems used in the diagnosis of
      tuberculosis in children.
AB  - Background. Tuberculosis (TB) is difficult to diagnose in children due to lack of
      a gold standard, especially in resource-limited settings. Scoring systems and
      diagnostic criteria are often used to assist in diagnosis; however their
      validity, especially in areas with high HIV prevalence, remains unclear. Methods.
      We searched online bibliographic databases, including MEDLINE and EMBASE. We
      selected all studies involving scoring systems or diagnostic criteria used to aid
      in the diagnosis of tuberculosis in children and extracted data from these
      studies. Results. The search yielded 2261 titles, of which 40 met selection
      criteria. Eighteen studies used point-based scoring systems. Eighteen studies
      used diagnostic criteria. Validation of these scoring systems yielded varying
      sensitivities as gold standards used ranged widely. Four studies evaluated and
      compared multiple scoring criteria. Ten studies selected for pulmonary
      tuberculosis. Five studies specifically evaluated the use of scoring systems in
      HIV-positive children, generally finding the specificity to be lower.
      Conclusions. Though scoring systems and diagnostic criteria remain widely used in
      the diagnosis of tuberculosis in children, validation has been difficult due to
      lack of an established and accessible gold standard. Estimates of sensitivity and
      specificity vary widely, especially in populations with high HIV co-infection.

PMID- 22848800
TI  - Age Differences among Female Sex Workers in the Philippines: Sexual Risk
      Negotiations and Perceived Manager Advice.
AB  - Consistent condom use among high risk groups such as female sex workers (FSWs)
      remains low. Adolescent female sex workers are especially at higher risk for
      HIV/STI infections. However, few published studies have compared the sexual risk
      negotiations among adolescent, emerging adult, and older age groups or the extent
      a manager's advice about condom use is associated with an FSW's age. Of 1,388
      female bar/spa workers surveyed in the southern Philippines, 791 FSW who traded
      sex in the past 6 months were included in multivariable logistic regression
      models. The oldest FSWs (aged 36-48) compared to adolescent FSWs (aged 14-17)
      were 3.3 times more likely to negotiate condoms when clients refused condom use.
      However, adolescent FSWs received more advice from their managers to convince
      clients to use condoms or else to refuse sex, compared to older FSWs. Both
      adolescent and the oldest FSWs had elevated sexually transmitted infections
      (STIs) and inconsistent condom use compared to other groups. Having a condom rule
      at the establishment was positively associated with condom negotiation. Factors
      such as age, the advice managers give to their workers, and the influence of a
      condom use rule at the establishment need to be considered when delivering
      HIV/STI prevention interventions.

PMID- 22848801
TI  - The prevalence of dyslipidemia in patients with spinal cord lesion in Thailand.
AB  - Objective. To assess the prevalence of dyslipidemia in 90 patients with spinal
      cord lesion (SCL) of duration greater than 2 years. The study was carried out
      from November 2007 to September 2008. Methods. Clinical history, physical
      examination, and lipid profiles were recorded and analyzed. Dyslipidemia was
      assessed using guidelines from the National Cholesterol Education Project Adult
      Treatment Panel III (ATP III). Results. The prevalence of dyslipidemia in at
      least one lipid parameter was 76.7%. The most frequent finding was low HDL-C
      (58.9%). Hypertriglyceridemia, hypercholesterolemia and high LDL-C were found in
      28.9%, 26.7% and 21.1% of patients, respectively. The factors sex = male and age
      >=45 years were associated with high LDL-C (P < 0.05 and P < 0.01). Patients who
      exercised less than 30 minutes per day had associated hypercholesterolemia (P <
      0.01), hypertriglyceridemia (P < 0.01), and higher LDL-C (P < 0.05). Patients
      with BMI >=23 kg/m(2) had associated hypercholesterolemia and high LDL-C. Age was
      a significant determinant of high LDL-C. BMI was the most powerful and
      significant determinant of hypercholesterolemia and high LDL-C. Conclusion. SCL
      patients should have a regular lipid checkup, especially those patients having
      the following risk factors: males, age >=45 years, BMI >=23 kg/m(2) and exercise
      duration <30 minutes per day.

PMID- 22848802
TI  - Brief group intervention using emotional freedom techniques for depression in
      college students: a randomized controlled trial.
AB  - Two hundred thirty-eight first-year college students were assessed using the Beck
      Depression Inventory (BDI). Thirty students meeting the BDI criteria for moderate
      to severe depression were randomly assigned to either a treatment or control
      group. The treatment group received four 90-minute group sessions of EFT
      (Emotional Freedom Techniques), a novel treatment that combines exposure,
      cognitive reprocessing, and somatic stimulation. The control group received no
      treatment. Posttests were conducted 3 weeks later on those that completed all
      requirements (N = 18). The EFT group (n = 9) had significantly more depression at
      baseline than the control group (n = 9) (EFT BDI mean = 23.44, SD = 2.1 versus
      control BDI mean = 20.33, SD = 2.1). After controlling for baseline BDI score,
      the EFT group had significantly less depression than the control group at
      posttest, with a mean score in the "nondepressed" range (P = .001; EFT BDI mean =
      6.08, SE = 1.8 versus control BDI mean = 18.04, SE = 1.8). Cohen's d was 2.28,
      indicating a very strong effect size. These results are consistent with those
      noted in other studies of EFT that included an assessment for depression and
      indicate the clinical usefulness of EFT as a brief, cost-effective, and
      efficacious treatment.

PMID- 22848803
TI  - Oncologic safety of skin-sparing and nipple-sparing mastectomy: a discussion and
      review of the literature.
AB  - Breast conservation therapy has been the cornerstone of the surgical treatment of
      breast cancer for the last 20 years; however, recently, the use of mastectomy has
      been increasing. Mastectomy is one of the most frequently performed breast
      operations, and with novel surgical techniques, preservation of the skin envelope
      and/or the nipple-areolar complex is commonly performed. The goal of this paper
      is to review the literature on skin-sparing mastectomy and nipple-sparing
      mastectomy and to evaluate the oncologic safety of these techniques. In addition,
      this paper will discuss the oncologic importance of margin status and type of
      mastectomy as it pertains to risk of local recurrence and relative need for
      adjuvant therapy.

PMID- 22848804
TI  - Preceptorship and mentorship.

PMID- 22848805
TI  - Minimal invasive percutaneous fixation of thoracic and lumbar spine fractures.
AB  - We studied 122 patients with 163 fractures of the thoracic and lumbar spine
      undergoing the surgical treatment by percutaneous transpedicular fixation and
      stabilization with minimally invasive technique. Patient followup ranged from 6
      to 72 months (mean 38 months), and the patients were assessed by clinical and
      radiographic evaluation. The results show that percutaneous transpedicular
      fixation and stabilization with minimally invasive technique is an adequate and
      satisfactory procedure to be used in specific type of the thoracolumbar and
      lumbar spine fractures.

PMID- 22848806
TI  - Treatment of inverted nipple with subareolar abscess: usefulness of high
      resolution MRI for preoperative evaluation.
AB  - Background. Inverted nipples with subareolar abscesses can recur due to
      insufficient resection. It is important to provide reliable curative treatment
      after determination of the extent of resection by preoperative imaging
      evaluation. Methods. Ten patients were treated for inverted nipples with
      subareolar abscess. Sonography and high-resolution MRI were used as preoperative
      imaging modalities. The endpoints of preoperative imaging evaluation were defined
      as the identification of the abscess site, isolated fistula site, and extent of
      inflammation. Results. In all patients, sonography confirmed the presence of
      abscesses but their locations could not be identified. Sonography could not
      confirm the presence of isolated fistula or inflammation. In contrast, high
      resolution MRI not only confirmed the presence of abscesses but also revealed
      their positional relationships with the nipples. In addition, high-resolution MRI
      confirmed the presence of isolated fistulas and inflammation as well as revealed
      their positional relationships with the nipples. In all patients, no recurrence
      was observed, and satisfactory surgical results were obtained. Conclusion. High
      resolution MRI is useful in determination of the extent of resection of
      subareolar abscess associated with inverted nipple.

PMID- 22848807
TI  - Actual situation of thromboembolic prophylaxis in obesity surgery: data of
      quality assurance in bariatric surgery in Germany.
AB  - Background. Evidence-based data on optimal approach for prophylaxis of deep
      venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is
      discussed. Using antithrombotic prophylaxis weight adjusted the risk of VTE and
      its complications have to be balanced with the increased bleeding risk. Methods.
      Since 2005 the current situation for bariatric surgery has been examined by
      quality assurance study in Germany. As a prospective multicenter observational
      study, data on the type, regimen, and time course of VTE prophylaxis were
      documented. The incidences of clinically diagnosed VTE or PE were derived during
      the in-hospital course and follow up. Results. Overall, 11,835 bariatric
      procedures were performed between January 2005 and December 2010. Most performed
      procedures were 2730 gastric banding (GB); 4901 Roux-en-Y-gastric bypass (RYGBP)
      procedures, and 3026 sleeve gastrectomies (SG). Study collective includes 72.5%
      (mean BMI 48.1 kg/m(2)) female and 27.5% (mean BMI 50.5 kg/m(2)) male patients.
      Incidence of VTE was 0.06% and of PE 0.08%. Conclusion. VTE prophylaxis regimen
      depends on BMI and the type of procedure. Despite the low incidence of VTE and PE
      there is a lack of evidence. Therefore, prospective randomized studies are
      necessary to determine the optimal VTE prophylaxis for bariatric surgical
      patients.

PMID- 22848808
TI  - Pouched rats' detection of tuberculosis in human sputum: comparison to culturing
      and polymerase chain reaction.
AB  - Setting. Tanzania. Objective. To compare microscopy as conducted in direct
      observation of treatment, short course centers to pouched rats as detectors of
      Mycobacterium tuberculosis. Design. Ten pouched rats were trained to detect
      tuberculosis in sputum using operant conditioning techniques. The rats evaluated
      910 samples previously evaluated by smear microscopy. All samples were also
      evaluated through culturing and multiplex polymerase chain reaction was performed
      on culture growths to classify the bacteria. Results. The patientwise sensitivity
      of microscopy was 58.0%, and the patient-wise specificity was 97.3%. Used as a
      group of 10 with a cutoff (defined as the number of rat indications to classify a
      sample as positive for Mycobacterium tuberculosis) of 1, the rats increased new
      case detection by 46.8% relative to microscopy alone. The average samplewise
      sensitivity of the individual rats was 68.4% (range 61.1-73.8%), and the mean
      specificity was 87.3% (range 84.7-90.3%). Conclusion. These results suggest that
      pouched rats are a valuable adjunct to, and may be a viable substitute for,
      sputum smear microscopy as a tuberculosis diagnostic in resource-poor countries.

PMID- 22848809
TI  - Comparative Analysis between SPECT Myocardial Perfusion Imaging and CT Coronary
      Angiography for Diagnosis of Coronary Artery Disease.
AB  - The study aims to discuss the relationship and difference between myocardial
      perfusion imaging (MPI) using SPECT and CT coronary angiography (CTCA) for
      diagnosis of coronary artery disease (CAD). Five hundred and four cases
      undergoing MPI and CTCA were comparatively analyzed, including fifty six patients
      undergoing invasive coronary angiography in the same period. Among patients with
      negative MPI results, negative or positive CTCA occupied 84.7% or 15.3%,
      respectively. Among patients with positive MPI, positive or negative CTCA
      occupied 67.2% or 32.8%, respectively. Among patients with negative CTCA,
      negative or positive MPI occupied 94.4% or 5.6%, respectively. Among patients
      with positive CTCA, positive or negative MPI occupied 40.2% or 59.8%,
      respectively. Negative predictive value was relatively higher than the positive
      predictive value for positive CTCA eliminating or predicting abnormal
      haemodynamics. And there was no significant difference for sensitivity,
      specificity, and accuracy of MPI or CTCA in diagnosing CAD. Both MPI and CTCA
      have good diagnostic performance for CAD. They provide different and
      complementary information for diagnosis and evaluation of CAD, namely, detection
      of ischemia versus detection of atherosclerosis, which are quite different but
      have a definite internal link for each other.

PMID- 22848812
TI  - Elimination of the actin-binding domain in kelch-like 1 protein induces T-type
      calcium channel modulation only in the presence of action potential waveforms.
AB  - The Kelch-like 1 protein (KLHL1) is a neuronal actin-binding protein that
      modulates calcium channel function. It increases the current density of Ca(v)3.2
      (alpha(1H)) calcium channels via direct interaction with alpha(1H) and actin-F,
      resulting in biophysical changes in Ca(v)3.2 currents and an increase in
      recycling endosomal activity with subsequent increased alpha(1H) channel number
      at the plasma membrane. Interestingly, removal of the actin-binding Kelch motif
      (DeltaKelch) prevents the increase in Ca(v)3.2 current density seen with wild
      type KLHL1 when tested with normal square pulse protocols but does not preclude
      the effect when tested using action potential waveforms (AP). Here, we dissected
      the kinetic properties of the AP waveform that confer the mutant Kelch the
      ability to interact with Ca(v)3.2 and induce an increase in calcium influx. We
      modified the action potential waveform by altering the slopes of repolarization
      and/or recovery from hyperpolarization or by changing the duration of the
      depolarization plateau or the hyperpolarization phase and tested the modulation
      of Ca(v)3.2 by the mutant DeltaKelch. Our results show that the recovery phase
      from hyperpolarization phase determines the conformational changes that allow the
      alpha(1H) subunit to properly interact with mutant KLHL1 lacking its actin
      binding Kelch domains, leading to increased Ca influx.

PMID- 22848811
TI  - Receptor tyrosine kinases: molecular switches regulating CNS axon regeneration.
AB  - The poor or lack of injured adult central nervous system (CNS) axon regeneration
      results in devastating consequences and poor functional recovery. The interplay
      between the intrinsic and extrinsic factors contributes to robust inhibition of
      axon regeneration of injured CNS neurons. The insufficient or lack of trophic
      support for injured neurons is considered as one of the major obstacles
      contributing to their failure to survive and regrow their axons after injury. In
      the CNS, many of the signalling pathways associated with neuronal survival and
      axon regeneration are regulated by several classes of receptor tyrosine kinases
      (RTK) that respond to a variety of ligands. This paper highlights and summarises
      the most relevant recent findings pertinent to different classes of the RTK
      family of molecules, with a particular focus on elucidating their role in CNS
      axon regeneration.

PMID- 22848810
TI  - Regulation of adherens junction dynamics by phosphorylation switches.
AB  - Adherens junctions connect the actin cytoskeleton of neighboring cells through
      transmembrane cadherin receptors and a network of adaptor proteins. The
      interactions between these adaptors and cadherin as well as the activity of actin
      regulators localized to adherens junctions are tightly controlled to facilitate
      cell junction assembly or disassembly in response to changes in external or
      internal forces and/or signaling. Phosphorylation of tyrosine, serine, or
      threonine residues acts as a switch on the majority of adherens junction
      proteins, turning "on" or "off" their interactions with other proteins and/or
      their enzymatic activity. Here, we provide an overview of the kinases and
      phosphatases regulating phosphorylation of adherens junction proteins and bring
      examples of phosphorylation events leading to the assembly or disassembly of
      adherens junctions, highlighting the important role of phosphorylation switches
      in regulating their dynamics.

PMID- 22848813
TI  - The phosphorylation-dependent regulation of mitochondrial proteins in stress
      responses.
AB  - To maintain cellular homeostasis, cells are equipped with precise systems that
      trigger the appropriate stress responses. Mitochondria not only provide cellular
      energy but also integrate stress response signaling pathways, including those
      regulating cell death. Several lines of evidence suggest that the mitochondrial
      proteins that function in this process, such as Bcl-2 family proteins in
      apoptosis and phosphoglycerate mutase family member 5 (PGAM5) in necroptosis, are
      regulated by several kinases. It has also been suggested that the phosphorylation
      dependent regulation of mitochondrial fission machinery, dynamin-related protein
      1 (Drp1), facilitates appropriate cellular stress responses. However,
      mitochondria themselves are also damaged by various stresses. To avoid the
      deleterious effects exerted by damaged mitochondria, cells remove these
      mitochondria in a selective autophagic degradation process called mitophagy.
      Interestingly, several kinases, such as PTEN-induced putative kinase 1 (PINK1) in
      mammals and stress-responsive mitogen-activated protein (MAP) kinases in yeast,
      have recently been shown to be involved in mitophagy. In this paper, we focus on
      the phosphorylation-dependent regulation of mitochondrial proteins and discuss
      the roles of this regulation in the mitochondrial and cellular stress responses.

PMID- 22848815
TI  - Significant Differences in Markers of Oxidant Injury between Idiopathic and
      Bronchopulmonary-Dysplasia-Associated Pulmonary Hypertension in Children.
AB  - While oxidant stress is elevated in adult forms of pulmonary hypertension (PH),
      levels of oxidant stress in pediatric PH are unknown. The objective of this study
      is to measure F(2)-isoprostanes, a marker of oxidant stress, in children with
      idiopathic pulmonary hypertension (IPH) and PH due to bronchopulmonary dysplasia
      (BPD). We hypothesized that F(2)-isoprostanes in pediatric IPH and PH associated
      with BPD will be higher than in controls. Plasma F(2)-isoprostanes were measured
      in pediatric PH patients during clinically indicated cardiac catheterization and
      compared with controls. F(2)-Isoprostane levels were compared between IPH, PH due
      to BD, and controls. Five patients with IPH, 12 with PH due to BPD, and 20
      control subjects were studied. Patients with IPH had statistically higher
      isoprostanes than controls 62 pg/mL (37-210) versus 20 pg/mL (16-27), P < 0.01).
      The patients with PH and BPD had significantly lower isoprostanes than controls
      15 pg/mL (8-17) versus 20 pg/ml (16-27), P < 0.02. F(2)-isoprostanes are elevated
      in children with IPH compared to both controls and patients with PH secondary to
      BPD. Furthermore, F(2)-isoprostanes in PH secondary to BPD are lower than control
      levels. These findings suggest that IPH and PH secondary to BPD have distinct
      mechanisms of disease pathogenesis.

PMID- 22848816
TI  - Clinical outcomes of stereotactic body radiotherapy for patients with lung tumors
      in the state of oligo-recurrence.
AB  - We retrospectively evaluated the clinical outcomes of patients with
      oligometastatic lung tumors who underwent stereotactic body radiotherapy (SBRT).
      Twenty-two patients with one or two oligometastatic lung tumors were treated with
      SBRT at our institution between 1999 and 2009. With a median follow-up period of
      25 months from the date of SBRT to the detection of oligometastatic lung tumors,
      the patients' 3- and 5-year overall survival (OS) and progression-free survival
      (PFS) rates were 72% and 54%, respectively. The median disease-free interval
      (DFI) between the treatment of the primary site and SBRT to oligometastatic lung
      tumors was 41 months. The OS of patients with a DFI >= 36 months was
      significantly longer than that of the patients with a DFI < 36 months by the log
      rank test (P = 0.02). For patients with a DFI >= 36 months, the 3- and 5-year OS
      rates were both 88%, compared to 50% for the patients with a DFI < 36 months. The
      primary tumor of all patients was locally controlled when SBRT to oligometastatic
      lung tumors was performed, and thus they were in the state of "oligo-recurrence."
      Patients with oligometastatic lung lesions treated by SBRT had good prognoses.
      This was especially true of the patients with a long DFI and in the state of
      "oligo-recurrence."

PMID- 22848814
TI  - Etiopathogenetic mechanisms of pulmonary hypertension in sleep-related breathing
      disorders.
AB  - Obstructive sleep apnea syndrome is a common disorder with significant health
      consequences and is on the rise in consonance with the obesity pandemic. In view
      of the association between sleep-disordered breathing and pulmonary hypertension
      as depicted by multiple studies, current clinical practice guidelines categorize
      obstructive sleep apnea as a risk factor for pulmonary hypertension and recommend
      an assessment for sleep disordered breathing in evaluating patients with
      pulmonary hypertension. The dysregulatory mechanisms associated with hypoxemic
      episodes observed in sleep related breathing disorders contribute to the onset of
      pulmonary hypertension and identification of these potentially treatable factors
      might help in the reduction of overall cardiovascular mortality.

PMID- 22848817
TI  - Pulmonary hypertension in pregnancy: critical care management.
AB  - Pulmonary hypertension is common in critical care settings and in presence of
      right ventricular failure is challenging to manage. Pulmonary hypertension in
      pregnant patients carries a high mortality rates between 30-56%. In the past
      decade, new treatments for pulmonary hypertension have emerged. Their application
      in pregnant women with pulmonary hypertension may hold promise in reducing
      morbidity and mortality. Signs and symptoms of pulmonary hypertension are
      nonspecific in pregnant women. Imaging workup may have undesirable radiation
      exposure. Pulmonary artery catheter remains the gold standard for diagnosing
      pulmonary hypertension, although its use in the intensive care unit for other
      conditions has slowly fallen out of favor. Goal-directed bedside echocardiogram
      and lung ultrasonography provide attractive alternatives. Basic principles of
      managing pulmonary hypertension with right ventricular failure are maintaining
      right ventricular function and reducing pulmonary vascular resistance. Fluid
      resuscitation and various vasopressors are used with caution. Pulmonary
      hypertension-targeted therapies have been utilized in pregnant women with
      understanding of their safety profile. Mainstay therapy for pulmonary embolism is
      anticoagulation, and the treatment for amniotic fluid embolism remains supportive
      care. Multidisciplinary team approach is crucial to achieving successful outcomes
      in these difficult cases.

PMID- 22848818
TI  - The effect of ventilation, age, and asthmatic condition on ultrafine particle
      deposition in children.
AB  - Ultrafine particles (UFPs) contribute to health risks associated with air
      pollution, especially respiratory disease in children. Nonetheless, experimental
      data on UFP deposition in asthmatic children has been minimal. In this study, the
      effect of ventilation, developing respiratory physiology, and asthmatic condition
      on the deposition efficiency of ultrafine particles in children was explored.
      Deposited fractions of UFP (10-200 nm) were determined in 9 asthmatic children, 8
      nonasthmatic children, and 5 nonasthmatic adults. Deposition efficiencies in
      adults served as reference of fully developed respiratory physiologies. A
      validated deposition model was employed as an auxiliary tool to assess the
      independent effect of varying ventilation on deposition. Asthmatic conditions
      were confirmed via pre-and post-bronchodilator spirometry. Subjects were exposed
      to a hygroscopic aerosol with number geometric mean diameter of 27-31 nm,
      geometric standard deviation of 1.8-2.0, and concentration of 1.2 * 10(6)
      particles cm(-3). Exposure was through a silicone mouthpiece. Total deposited
      fraction (TDF) and normalized deposition rate were 50% and 32% higher in children
      than in adults. Accounting for tidal volume and age variation, TDF was 21% higher
      in asthmatic than in non-asthmatic children. The higher health risks of air
      pollution exposure observed in children and asthmatics might be augmented by
      their susceptibility to higher dosages of UFP.

PMID- 22848819
TI  - Mechanisms of perinatal brain injury.

PMID- 22848820
TI  - Magnetic resonance imaging in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative
      disorder which is incurable to date. As there are many ongoing studies with
      therapeutic candidates, it is of major interest to develop biomarkers not only to
      facilitate early diagnosis but also as a monitoring tool to predict disease
      progression and to enable correct randomization of patients in clinical trials.
      Magnetic resonance imaging (MRI) has made substantial progress over the last
      three decades and is a practical, noninvasive method to gain insights into the
      pathology of the disease. Disease-specific MRI changes therefore represent
      potential biomarkers for ALS. In this paper we give an overview of structural and
      functional MRI alterations in ALS with the focus on task-free resting-state
      investigations to detect cortical network failures.

PMID- 22848822
TI  - The radiology fellowship application and selection process in the United States:
      experiences and perceptions from both sides.
AB  - Objective. Our purpose was to investigate radiology fellowship directors' and
      recent fellows' experiences and perceptions with regard to the fellowship
      application and selection process and to compare these experiences and
      perceptions. Materials and Methods. Institutional review board approval was
      obtained. We conducted an online survey of the memberships of three radiology
      subspecialty societies between October 2009 and December 2009 to learn about
      radiologists' views regarding various aspects of radiology fellowships. Results.
      In the process of selecting fellows, program directors and recent fellows
      consider performance during the radiology residency and the quality or prestige
      of the residency program as the most important objective factors, and the
      personal interview, letters of recommendation, and personality as the most
      important subjective factors. 25% of the program directors were in the match, and
      41% of the recent fellows were in the match. Most (48%) of program directors
      favored a match, but most (56%) of the recent fellows disfavored participating in
      a match. Both program directors and recent fellows expressed satisfaction with
      the fellowship application and selection process. Conclusion. There was no
      majority support for a fellowship match among program directors and recent
      fellows and less support among recent fellows. Recent fellows appear more
      satisfied with the current selection and application process than program
      directors.

PMID- 22848821
TI  - Preoperative evaluation with FMRI of patients with intracranial gliomas.
AB  - Introduction. Aggressive surgical resection constitutes the optimal treatment for
      intracranial gliomas. However, the proximity of a tumor to eloquent areas
      requires exact knowledge of its anatomic relationships to functional cortex. The
      purpose of our study was to evaluate fMRI's accuracy by comparing it to
      intraoperative cortical stimulation (DCS) mapping. Material and Methods. Eighty
      seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and
      intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI
      and DCS were considered concordant if the identified cortical centers were less
      than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer
      scores were recorded. A postoperative MRI was obtained for assessing the extent
      of resection. Results. The areas of interest were identified by fMRI and DCS in
      all participants. The concordance between fMRI and DCS was 91.9% regarding
      sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data
      analysis showed that patients with better functional condition demonstrated
      higher concordance rates, while there also was a weak association between tumor
      grade and concordance rate. The mean extent of tumor resection was 96.7%.
      Conclusions. Functional MRI is a highly accurate preoperative methodology for
      sensory-motor mapping. However, in language mapping, DCS remains necessary for
      accurate localization.

PMID- 22848823
TI  - Prevalence of chronic kidney disease and its association with risk factors in
      disadvantageous population.
AB  - The prevalence of kidney disease, particularly diabetic and hypertensive kidney
      disease is increasing rapidly specially in the disadvantageous group of
      population throughout the world. A cross sectional survey was carried out at
      certain selected slum areas of Mirpur in Dhaka city of Bangladesh over the period
      from July 2003 to June 2005, and a total of participants ranging from 15 to 65
      years were studied. The analysis discovered that 4.1% of the participants were
      diabetic, 11.6% were hypertensive, and 7.7% had proteinuria. Based on MDRD
      equation, 13.1% of the participants were detected as having chronic kidney
      disease (CKD) while with Cockcroft-Gault equation 16% had CKD. Accordingly, the
      difference between the two equations was not significant. Association of
      sociodemographic factors with CKD was not significant except age more than 40
      years and marital status. The association between CKD and risk factors like
      proteinuria, obese and overweight, use of tobacco, diabetes mellitus, and
      hypertension was highly significant. Combined prevalence of DM, hypertension, and
      proteinuria among CKD group was also demonstrated to be significantly higher
      (3.8% with Cockcroft-Gault equation and 5.3% with MDRD equation) than that of
      normal population. The survey data revealed that CKD and its risk factors like DM
      and hypertension are alarmingly high in disadvantageous population and adding
      further pressure to the existing burden of CKD.

PMID- 22848824
TI  - Duplex ultrasound evaluation of hemodialysis access: a detailed protocol.
AB  - A detailed protocol for the performance and interpretation of duplex ultrasound
      evaluation of hemodialysis access is described.

PMID- 22848825
TI  - The Continuing Evolution of HIV-1 Therapy: Identification and Development of
      Novel Antiretroviral Agents Targeting Viral and Cellular Targets.
AB  - During the past three decades, over thirty-five anti-HIV-1 therapies have been
      developed for use in humans and the progression from monotherapeutic treatment
      regimens to today's highly active combination antiretroviral therapies has had a
      dramatic impact on disease progression in HIV-1-infected individuals. In spite of
      the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse
      transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still
      have a variety of problems which require continued development efforts to improve
      efficacy and reduce toxicity, while making drugs that can be used throughout both
      the developed and developing world, in pediatric populations, and in pregnant
      women. Highly active antiretroviral therapies (HAARTs) have significantly delayed
      the progression to AIDS, and in the developed world HIV-1-infected individuals
      might be expected to live normal life spans while on lifelong therapies. However,
      the difficult treatment regimens, the presence of class-specific drug toxicities,
      and the emergence of drug-resistant virus isolates highlight the fact that
      improvements in our therapeutic regimens and the identification of new and novel
      viral and cellular targets for therapy are still necessary. Antiretroviral
      therapeutic strategies and targets continue to be explored, and the development
      of increasingly potent molecules within existing classes of drugs and the
      development of novel strategies are ongoing.

PMID- 22848826
TI  - Factors Important to the Prioritization and Development of Successful Topical
      Microbicides for HIV-1.
AB  - Significant advancements in topical microbicide development have occurred since
      the prevention strategy was first described as a means to inhibit the sexual
      transmission of HIV-1. The lack of clinical efficacy of the first generation
      microbicide products has focused development attention on specific antiretroviral
      agents, and these agents have proven partially successful in human clinical
      trials. With greater understanding of vaginal and rectal virus infection,
      replication, and dissemination, better microbicide products and delivery
      strategies should result in products with enhanced potency. However, a variety of
      development gaps exist which relate to product dosing, formulation and delivery,
      and pharmacokinetics and pharmacodynamics which must be better understood in
      order to prioritize microbicide products for clinical development. In vitro, ex
      vivo, and in vivo models must be optimized with regard to these development gaps
      in order to put the right product at the right place, at the right time, and at
      the right concentration for effective inhibition of virus transmission. As the
      microbicide field continues to evolve, we must harness the knowledge gained from
      unsuccessful and successful clinical trials and development programs to
      continuously enhance our preclinical development algorithms.

PMID- 22848827
TI  - Physical Activity among Veterans and Nonveterans with Diabetes.
AB  - Engaging in regular physical activity (PA), with or without a corresponding
      decrease in weight, is associated with improved health outcomes. The purpose of
      this study was to quantify the extent to which PA differed between veterans and
      nonveterans and to determine how diabetes and age influenced this association.
      Data from the 2009 Behavioral Risk Factor Surveillance System were used in this
      study. Respondents were classified as having diabetes if they reported ever being
      diagnosed with diabetes except during pregnancy. Respondents who reported ever
      serving on active military duty were classified as veterans. Based on self
      report, we calculated the average minutes per week of moderate, vigorous, and
      total activity. After adjusting for sex, race and ethnicity, household income,
      education level, body mass index (BMI), and recent health checkup, veteran status
      was associated with a small but significantly larger amount of average weekly
      moderate PA (2.2 minutes, P = 0.0058) but not average weekly vigorous PA (-0.02
      minutes, P = 0.98). Diabetes and prediabetes were associated with significantly
      lower mean levels of both moderate and vigorous intensity PA, as was increasing
      age. Consistent with prior research, veterans engaged in more PA than
      nonveterans. The association between diabetes, age, and physical activity did not
      differ by veteran status.

PMID- 22848829
TI  - Preventive treatments of iron deficiency anaemia in pregnancy: a review of their
      effectiveness and implications for health system strengthening.
AB  - OBJECTIVES: We conducted a review of effectiveness of preventive treatments of
      iron deficiency anaemia in pregnancy in developing countries and highlighted
      their constraints as well as interventions required to strengthen the health
      services. Methods. Literature from Pubmed (MEDLINE), AJOL, Google Scholar, and
      Cochrane database was reviewed. RESULTS: Evidence-based preventive treatment
      options for iron deficiency anaemia in pregnancy include prophylaxis iron
      supplements and food fortification with iron. Evidence abounds on their
      effectiveness in reducing the prevalence of iron deficiency anaemia in pregnancy.
      However, these prospects are threatened by side effects of iron supplements, low
      utilization of maternal health service in developing countries, partial
      implementation of preventive treatments, and weak infrastructure and political
      commitment to implement mass fortification of local staple foods by national
      governments. CONCLUSION: Sustainability of effectiveness of preventive treatments
      of iron deficiency anaemia in pregnancy could be achieved if the identified
      threats are adequately addressed.

PMID- 22848828
TI  - Effect of atypical antipsychotics on fetal growth: is the placenta involved?
AB  - There is currently considerable uncertainty regarding prescribing practices for
      pregnant women with severe and persistent psychiatric disorders. The physician
      and the mother have to balance the risks of untreated psychiatric illness against
      the potential fetal toxicity associated with pharmacological exposure. This is
      especially true for women taking atypical antipsychotics. Although these drugs
      have limited evidence for teratological risk, there are reports of altered fetal
      growth, both increased and decreased, with maternal atypical antipsychotic use.
      These effects may be mediated through changes in the maternal metabolism which in
      turn impacts placental function. However, the presence of receptors targeted by
      atypical antipsychotics in cell lineages present in the placenta suggests that
      these drugs can also have direct effects on placental function and development.
      The signaling pathways involved in linking the effects of atypical antipsychotics
      to placental dysfunction, ultimately resulting in altered fetal growth, remain
      elusive. This paper focuses on some possible pathways which may link atypical
      antipsychotics to placental dysfunction.

PMID- 22848830
TI  - Impact of oxidative stress in fetal programming.
AB  - Intrauterine stress induces increased risk of adult disease through fetal
      programming mechanisms. Oxidative stress can be generated by several conditions,
      such as, prenatal hypoxia, maternal under- and overnutrition, and excessive
      glucocorticoid exposure. The role of oxidant molecules as signaling factors in
      fetal programming via epigenetic mechanisms is discussed. By linking oxidative
      stress with dysregulation of specific target genes, we may be able to develop
      therapeutic strategies that protect against organ dysfunction in the programmed
      offspring.

PMID- 22848832
TI  - Thyroid dysfunction and autoantibodies association with hypertensive disorders
      during pregnancy.
AB  - BACKGROUND: Thyroid dysfunction and autoimmunity are relatively common in
      reproductive age and have been associated with adverse health outcomes for both
      mother and child, including hypertensive disorders during pregnancy. Objective.
      To survey the relation between thyroid dysfunction and autoimmunity and incidence
      and severity of pregnancy-induced hypertensive disorders. METHOD: In this case
      control study 48 hypertensive patients in 4 subgroups (gestational hypertension,
      mild preeclampsia, severe preeclampsia, eclampsia) and 50 normotensive ones were
      studied. The samples were nulliparous and matched based on age and gestational
      age and none of them had previous history of hypertensive or thyroid disorders
      and other underlying systemic diseases or took medication that might affect
      thyroid function. Their venous blood samples were collected using
      electrochemiluminescence and ELISA method and thyroid hormones and TSH and
      autoantibodies were measured. RESULTS: Hypertensive patients had significant
      lower T3 concentration compared with normotensive ones with mean T3 values 152.5
      +/- 48.93 ng/dL, 175.36 +/- 58.07 ng/dL respectively. Anti-TPO concentration is
      higher in control group 6.07 +/- 9.02 IU/mL compared with 2.27 +/- 2.94 IU/mL in
      cases. CONCLUSION: The severity of preeclampsia and eclampsia was not associated
      with thyroid function tests. The only significant value was low T3 level among
      pregnancy, induced hypertensive patients.

PMID- 22848831
TI  - Preeclampsia 2012.
AB  - Preeclampsia is a common complication of pregnancy associated with high maternal
      morbidity and mortality and intrauterine fetal growth restriction. There is
      extensive evidence that the reduction of uteroplacental blood flow in this
      syndrome results from the toxic combination of hypoxia, imbalance of angiogenic
      and antiangiogenic factors, inflammation, and deranged immunity. Women treated
      for preeclampsia also have an increased risk for cardiovascular and renal
      disease. At present it is unclear if the increased cardiovascular and renal
      disease risks are due to residual and or progressive effects of endothelial
      damage from the preeclampsia or from shared risk factors between preeclampsia and
      cardiac disease. Moreover, it appears that endothelin-1 signaling may play a
      central role in the hypertension associated with preeclampsia. In this paper, we
      discuss emerging data on the pathogenesis of preeclampsia and review therapeutic
      options.

PMID- 22848833
TI  - Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced
      Myocardial Superoxide Production and Cardiac Remodeling.
AB  - Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular
      remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived
      cardioprotective factor, although its effect on cardiac superoxide generation has
      not been investigated in vivo. This study tested the hypothesis that suppression
      of superoxide production contributes to the cardioprotective action of CNP.
      Angiotensin II (Ang II) or saline was continuously infused subcutaneously into
      mice using an osmotic minipump. Simultaneously with the initiation of Ang II
      treatment, mice were infused with CNP (0.05 MUg/kg/min) or vehicle for 2 weeks.
      The heart weight to tibial length ratio was significantly increased by Ang II in
      vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac
      hypertrophy without affecting systolic blood pressure. Echocardiography showed
      that CNP attenuated Ang II-induced increase in wall thickness, left ventricular
      dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced
      increases in cardiomyocyte size and interstitial fibrosis and suppressed
      hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II
      induced cardiac superoxide production. These changes were accompanied by
      suppression of NOX4 gene expression. Our data indicate that treatment with CNP
      attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile
      dysfunction which were accompanied by reduced cardiac superoxide production.

PMID- 22848834
TI  - Anti-inflammatory effects of epoxyeicosatrienoic acids.
AB  - Epoxyeicosatrienoic acids (EETs) are generated by the activity of both selective
      and also more general cytochrome p450 (CYP) enzymes on arachidonic acid and
      inactivated largely by soluble epoxide hydrolase (sEH), which converts them to
      their corresponding dihydroxyeicosatrienoic acids (DHETs). EETs have been shown
      to have a diverse range of effects on the vasculature including relaxation of
      vascular tone, cellular proliferation, and angiogenesis as well as the migration
      of smooth muscle cells. This paper will highlight the growing evidence that EETs
      also mediate a number of anti-inflammatory effects in the cardiovascular system.
      In particular, numerous studies have demonstrated that potentiation of EET
      activity using different methods can inhibit inflammatory gene expression and
      signalling pathways in endothelial cells and monocytes and in models of
      cardiovascular diseases. The mechanisms by which EETs mediate their effects are
      largely unknown but may include direct binding to peroxisome proliferator
      activated receptors (PPARs), G-protein coupled receptors (GPCRs), or transient
      receptor potential (TRP) channels, which initiate anti-inflammatory signalling
      cascades.

PMID- 22848835
TI  - Self-Paced Walking within a Diverse Topographical Environment Elicits an
      Appropriate Training Stimulus for Cardiac Rehabilitation Patients.
AB  - Purpose. To assess the effect of a self-paced walking intervention within a
      topographically varied outdoor environment on physiological and perceptual
      markers in cardiac rehabilitation (CR) patients. Methods. Sixteen phase II CR
      patients completed twelve self-paced one-mile walking sessions over a four-week
      period within a community-based CR programme. Walking velocity, heart rate (HR),
      and ratings of perceived exertion (RPE) were reported at eight stages throughout
      the self-paced walks. Results. The study showed a significant increase in walking
      velocity from week 1 (~4.5 km/h) to week 4 (~5.1 km/h) of the self-paced walking
      programme (P < .05). A significantly higher HR was also observed in week 4 (111
      +/- 13 b.min(-1); ~69% of maximal HR) compared to week 1 (106 +/- 14 b.min(-1);
      ~65% of maximal HR, P < .001). There were no changes in the average RPE across
      the course of the 4-week self-paced walking programme (P > .05). Conclusion. A
      self-paced walking programme may elicit an appropriate training stimulus for CR
      patients when exercising within a diverse topographical environment. Participants
      completed a one-mile walk within a shorter period of time and at a higher
      physiological intensity than that elicited at the onset of the programme, despite
      no observed changes in participants' subjective perception of exertion.

PMID- 22848836
TI  - Traumatic brain injury in sports: a review.
AB  - Traumatic brain injury (TBI) is a clinical diagnosis of neurological dysfunction
      following head trauma, typically presenting with acute symptoms of some degree of
      cognitive impairment. There are an estimated 1.7 to 3.8 million TBIs each year in
      the United States, approximately 10 percent of which are due to sports and
      recreational activities. Most brain injuries are self-limited with symptom
      resolution within one week, however, a growing amount of data is now establishing
      significant sequelae from even minor impacts such as headaches, prolonged
      cognitive impairments, or even death. Appropriate diagnosis and treatment
      according to standardized guidelines are crucial when treating athletes who may
      be subjected to future head trauma, possibly increasing their likelihood of long
      term impairments.

PMID- 22848837
TI  - Manual wheelchair use: bouts of mobility in everyday life.
AB  - Background. This study aimed to describe how people move about in manual
      wheelchairs (MWCs) during everyday life by evaluating bouts of mobility or
      continuous periods of movement. Methods. A convenience sample of 28 MWC users was
      recruited. Participants' everyday mobility was measured using a wheel-mounted
      accelerometer and seat occupancy switch for 1-2 weeks. Bouts of mobility were
      recorded and characterized. Results. Across 29,200 bouts, the median bout lasted
      21 seconds and traveled 8.6 m at 0.43 m/s. 85% of recorded bouts lasted less than
      1 minute and traveled less than 30 meters. Participants' daily wheelchair
      activity included 90 bouts and 1.6 km over 54 minutes. Average daily occupancy
      time was 11 hours during which participants wheeled 10 bouts/hour and spent 10%
      of their time wheeling. Spearman-Brown Prophecy analysis suggested that 7 days
      were sufficient to achieve a reliability of 0.8 for all bout variables.
      Conclusions. Short, slow bouts dominate wheelchair usage in a natural
      environment. Therefore, clinical evaluations and biomechanical research should
      reflect this by concentrating on initiating movement, maneuvering wheelchairs,
      and stopping. Bouts of mobility provide greater depth to our understanding of
      wheelchair use and are a more stable metric (day-to-day) than distance or time
      wheeled.

PMID- 22848838
TI  - Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected
      Lesions: A Retrospective Chart Review.
AB  - This study examined whether patient-identified melanomas were more advanced than
      dermatologist-identified tumors at routine clinic visits, and whether a personal
      or family history of skin cancer was associated with patterns of detection. A
      retrospective chart review was performed on melanoma patients (N = 201) in a
      private dermatology clinic. Variables included age, gender, pattern of detection
      (i.e., patient or a board certified dermatologist), personal or family history of
      skin cancer, skin type, and previous sun exposure, as well as tumor location and
      severity. Dermatologist-diagnosed melanomas were less invasive (P < 0.0005), and
      more likely present on the chest, back, and legs (P < 0.01). Conversely, patient
      identified lesions were more likely to occur on the face, neck and scalp, be
      associated with younger patients, and a family history of melanoma, but not other
      types of skin cancer (P < 0.01). In a post-hoc analysis examining these factors
      as predictors of tumor invasiveness, only diagnostic source was significant.
      Specifically, dermatologist-identified tumors were significantly less invasive
      than patient-identified tumors. Although age, family history, and tumor location
      played roles in the early detection of melanomas, the most important factor was
      diagnostic source. Thus, board-certified dermatologists play a key role in the
      early detection of malignant melanoma.

PMID- 22848839
TI  - The phospholipid profile of mycoplasmas.
AB  - The de novo synthesized polar lipids of Mycoplasma species are rather simple,
      comprising primarily of the acidic glycerophospholipids PG and CL. In addition,
      when grown in a medium containing serum, significant amounts of PC and SPM are
      incorporated into the mycoplasma cell membrane although these lipids are very
      uncommon in wall-covered bacteria. The exogenous lipids are either incorporated
      unchanged or the PC incorporated is modified by a deacylation-acylation enzymatic
      cycle to form disaturated PC. Although their small genome, in some Mycoplasma
      species, other genes involved in lipid biosynthesis were detected, resulting in
      the synthesis of a variety of glycolipis, phosphoglycolipids and ether lipids. We
      suggest that analyses and comparisons of mycoplasma polar lipids may serve as a
      novel and useful tool for classification. Nonetheless, to evaluate the importance
      of polar lipids in mycoplasma, further systematic and extensive studies on more
      Mycoplasma species are needed. While studies are needed to elucidate the role of
      lipids in the mechanisms governing the interaction of mycoplasmas with host
      eukaryotic cells, the finding that a terminal phosphocholine containing
      glycolipids of M. fermentans serves both as a major immune determinants and as a
      trigger of the inflammatory responses, and the findings that the fusogenicity of
      M. fermentans with host cells is markedly stimulated by lyso-ether lipids, are
      important steps toward understanding the molecular mechanisms of M. fermentans
      pathogenicity.

PMID- 22848841
TI  - HOMA-AD in Assessing Insulin Resistance in Lean Noncirrhotic HCV Outpatients.
AB  - Introduction. There is an association between HCV and insulin resistance (IR),
      which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin
      (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose
      of this study was to evaluate IR in an HCV sample and controls, in order to
      compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients
      aged <60 years who met the criteria of nondiabetic, nonobese, noncirrhotic, and
      nonalcohol abusers were included and compared to 29 controls. Fasting glucose,
      insulin, adiponectin, and lipid profiles were determined. IR was estimated by
      HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but
      the HCV patients were older. The median insulin level was higher in the HCV group
      (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR
      (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of
      IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin
      levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent
      even in low-risk HCV outpatients. Adiponectin is not influenced by the presence
      of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.

PMID- 22848840
TI  - Hypofractionated proton boost combined with external beam radiotherapy for
      treatment of localized prostate cancer.
AB  - Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam
      radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients
      with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the
      patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium
      followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%,
      and 74% for low-, intermediate-, and high-risk patients, respectively. The
      toxicity evaluation was supported by a patient-reported questionnaire before
      every consultant visit. Cumulative probability and actuarial prevalence of
      genitourinary (GU) and gastrointestinal (GI) toxicities are presented according
      to the RTOG classification. N-ADT did not influence curability. Mild pretreatment
      GU-symptoms were found to be a strong predictive factor for GU-toxicity
      attributable to treatment. The actuarial prevalence declined over 3 to 5 years
      for both GU and GI toxicities, indicating slow resolution of epithelial damage to
      the genitourinary and gastrointestinal tract. Bladder toxicities rather than
      gastrointestinal toxicities seem to be dose limiting. More than 5-year followup
      is necessary to reveal any sign of true progressive late side effects of the
      given treatment. Hypofractionated proton-boost combined with EBRT is associated
      with excellent curability of localized PC and acceptable frequencies of treatment
      toxicity.

PMID- 22848842
TI  - Nurses' role in caring for women experiencing intimate partner violence in the
      sri lankan context.
AB  - Intimate partner violence has short- and long-term physical and mental health
      consequences. As the largest healthcare workforce globally, nurses are well
      positioned to care for abused women. However, their role in this regard has not
      been researched in some countries. This paper is based on a qualitative study
      that explored how Sri Lankan nurses perceive their role in caring for women who
      have experienced partner violence. Interviews with 30 nurses who worked in
      diverse clinical and geographical settings in Sri Lanka revealed that nurses'
      role involved: identifying abuse, taking care of patients' physical needs,
      attending to their safety, providing support and advice, and making referrals.
      Barriers to providing care included lack of knowledge; heavy workload; language
      barriers; threats to personal safety; nurses' status within the healthcare
      hierarchy; and lack of communication and collaboration between various
      stakeholder groups within the healthcare system. Nurses also identified a lack of
      appropriate services and support within hospitals and in the community. The
      findings reveal an urgent need for the healthcare system to respond to nurses'
      educational and training needs and help them function autonomously within
      multidisciplinary teams when caring for abused women. The findings also point to
      a need to address institutional barriers including the lack of appropriate
      services for abused women.

PMID- 22848843
TI  - Gemcitabine Plus Carboplatin in Patients with Advanced Hepatocellular Carcinoma:
      Results of a Phase II Study.
AB  - Objectives. Assessment of gemcitabine/carboplatin combination in patients with
      advanced-stage hepatocellular carcinoma (HCC) in a phase II trial for safety and
      efficacy. Methods. Forty patients with previously untreated advanced-stage HCC
      were prospectively enrolled and subjected to gemcitabine/carboplatin regimen
      which consisted of gemcitabine 1000 mg/m(2) on days 1 and 8, and carboplatin AUC
      6 on day 1. The treatment was repeated every 3 weeks until disease progression or
      limiting toxicity. Results. Forty patients were assessable for efficacy and
      toxicity. In all, 276 treatment cycles were administered. No toxic deaths
      occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of
      patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%).
      Grade 3 carboplatin-induced neurotoxicity was observed in 3 (9%) patients. ORR
      was 23% (95% CI, 0.10-0.29) with 9 partial responses and disease stabilization
      was observed in 46% (95% CI, 0.22-0.42) of patients, giving a disease control
      rate of 69%. Median progression-free and overall survival times were,
      respectively, 5 months (95% CI: 3-8 months) and 8 months (95% CI: 6-18 months).
      Conclusion. The gemcitabine/carboplatin regimen seems to be effective, well
      tolerated, and active in advanced HCC.

PMID- 22848844
TI  - From abnormal hippocampal synaptic plasticity in down syndrome mouse models to
      cognitive disability in down syndrome.
AB  - Down syndrome (DS) is caused by the overexpression of genes on triplicated
      regions of human chromosome 21 (Hsa21). While the resulting physiological and
      behavioral phenotypes vary in their penetrance and severity, all individuals with
      DS have variable but significant levels of cognitive disability. At the core of
      cognitive processes is the phenomenon of synaptic plasticity, a functional change
      in the strength at points of communication between neurons. A wide variety of
      evidence from studies on DS individuals and mouse models of DS indicates that
      synaptic plasticity is adversely affected in human trisomy 21 and mouse segmental
      trisomy 16, respectively, an outcome that almost certainly extensively
      contributes to the cognitive impairments associated with DS. In this review, we
      will highlight some of the neurophysiological changes that we believe reduce the
      ability of trisomic neurons to undergo neuroplasticity-related adaptations. We
      will focus primarily on hippocampal networks which appear to be particularly
      impacted in DS and where consequently the majority of cellular and neuronal
      network research has been performed using DS animal models, in particular the
      Ts65Dn mouse. Finally, we will postulate on how altered plasticity may contribute
      to the DS cognitive disability.

PMID- 22848845
TI  - Age-related deficits of dual-task walking: a review.
AB  - This review summarizes our present knowledge about elderly people's problems with
      walking. We highlight the plastic changes in the brain that allow a partial
      compensation of these age-related deficits and discuss the associated costs and
      limitations. Experimental evidence for the crucial role of executive functions
      and working memory is presented, leading us to the hypothesis that it is
      difficult for seniors to coordinate two streams of visual information, one
      related to navigation through visually defined space, and the other to a visually
      demanding second task. This hypothesis predicts that interventions aimed at the
      efficiency of visuovisual coordination in the elderly will ameliorate their
      deficits in dual-task walking.

PMID- 22848846
TI  - Molecular and cellular alterations in Down syndrome: toward the identification of
      targets for therapeutics.
AB  - Down syndrome is a complex disease that has challenged molecular and cellular
      research for more than 50 years. Understanding the molecular bases of
      morphological, cellular, and functional alterations resulting from the presence
      of an additional complete chromosome 21 would aid in targeting specific genes and
      pathways for rescuing some phenotypes. Recently, progress has been made by
      characterization of brain alterations in mouse models of Down syndrome. This
      review will highlight the main molecular and cellular findings recently described
      for these models, particularly with respect to their relationship to Down
      syndrome phenotypes.

PMID- 22848847
TI  - Astrocytes and developmental plasticity in fragile X.
AB  - A growing body of research indicates a pivotal role for astrocytes at the
      developing synapse. In particular, astrocytes are dynamically involved in
      governing synapse structure, function, and plasticity. In the postnatal brain,
      their appearance at synapses coincides with periods of developmental plasticity
      when neural circuits are refined and established. Alterations in the partnership
      between astrocytes and neurons have now emerged as important mechanisms that
      underlie neuropathology. With overall synaptic function standing as a prominent
      link to the expression of the disease phenotype in a number of neurodevelopmental
      disorders and knowing that astrocytes influence synapse development and function,
      this paper highlights the current knowledge of astrocyte biology with a focus on
      their involvement in fragile X syndrome.

PMID- 22848848
TI  - Synaptic plasticity and learning in animal models of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is caused by a mutation of either the Tsc1 or
      Tsc2 gene. As these genes work in concert to negatively regulate the mammalian
      target of rapamycin (mTOR) kinase which is involved in protein translation,
      mutations of these genes lead to a disinhibited mTOR activity. Both the clinical
      appearance of this condition including tumors, cognitive decline, and epileptic
      seizures and the molecular understanding of the mTOR signaling pathway, not only
      involved in cell growth, but also in neuronal functioning, have inspired numerous
      studies on learning behavior as well as on synaptic plasticity which is the key
      molecular mechanism of information storage in the brain. A couple of interesting
      animal models have been established, and the data obtained in these animals will
      be discussed. A special focus will be laid on differences among these models,
      which may be in part due to different background strains, but also may indicate
      pathophysiological variation in different mutations.

PMID- 22848849
TI  - Enriched and deprived sensory experience induces structural changes and rewires
      connectivity during the postnatal development of the brain.
AB  - During postnatal development, sensory experience modulates cortical development,
      inducing numerous changes in all of the components of the cortex. Most of the
      cortical changes thus induced occur during the critical period, when the
      functional and structural properties of cortical neurons are particularly
      susceptible to alterations. Although the time course for experience-mediated
      sensory development is specific for each system, postnatal development acts as a
      whole, and if one cortical area is deprived of its normal sensory inputs during
      early stages, it will be reorganized by the nondeprived senses in a process of
      cross-modal plasticity that not only increases performance in the remaining
      senses when one is deprived, but also rewires the brain allowing the deprived
      cortex to process inputs from other senses and cortices, maintaining the modular
      configuration. This paper summarizes our current understanding of sensory systems
      development, focused specially in the visual system. It delineates sensory
      enhancement and sensory deprivation effects at both physiological and anatomical
      levels and describes the use of enriched environment as a tool to rewire loss of
      brain areas to enhance other active senses. Finally, strategies to apply
      restorative features in human-deprived senses are studied, discussing the
      beneficial and detrimental effects of cross-modal plasticity in prostheses and
      sensory substitution devices implantation.

PMID- 22848850
TI  - Mouse brain PSA-NCAM levels are altered by graded-controlled cortical impact
      injury.
AB  - Traumatic brain injury (TBI) is a worldwide endemic that results in unacceptably
      high morbidity and mortality. Secondary injury processes following primary injury
      are composed of intricate interactions between assorted molecules that ultimately
      dictate the degree of longer-term neurological deficits. One comparatively
      unexplored molecule that may contribute to exacerbation of injury or enhancement
      of recovery is the posttranslationally modified polysialic acid form of neural
      cell adhesion molecule, PSA-NCAM. This molecule is a critical modulator of
      central nervous system plasticity and reorganization after injury. In this study,
      we used controlled cortical impact (CCI) to produce moderate or severe TBI in the
      mouse. Immunoblotting and immunohistochemical analysis were used to track the
      early (2, 24, and 48 hour) and late (1 and 3 week) time course and location of
      changes in the levels of PSA-NCAM after TBI. Variable and heterogeneous short-
      and long-term increases or decreases in expression were found. In general,
      alterations in PSA-NCAM levels were seen in the cerebral cortex immediately after
      injury, and these reductions persisted in brain regions distal to the primary
      injury site, especially after severe injury. This information provides a starting
      point to dissect the role of PSA-NCAM in TBI-related pathology and recovery.

PMID- 22848852
TI  - Homeostatic plasticity in the nervous system.

PMID- 22848851
TI  - Adult-onset fluoxetine treatment does not improve behavioral impairments and may
      have adverse effects on the Ts65Dn mouse model of Down syndrome.
AB  - Down syndrome is caused by triplication of chromosome 21 and is associated with
      neurocognitive phenotypes ranging from severe intellectual disability to various
      patterns of more selective neuropsychological deficits, including memory
      impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic
      neurotransmission results in local over-inhibition of hippocampal circuits, which
      dampens hippocampal synaptic plasticity and contributes to cognitive impairments.
      Treatments with several GABA(A) receptor antagonists result in increased
      plasticity and improved memory deficits in Ts65Dn mice. These GABA(A) receptor
      antagonists are, however, not suitable for clinical applications. The selective
      serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed
      antidepressant that can also enhance plasticity in the adult rodent brain by
      lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4
      week oral fluoxetine treatment restores spatial learning and memory impairments
      in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of
      Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine
      treated Ts65Dn mice, raising the possibility of a drug * genotype interaction
      with respect to these adverse treatment outcomes. Future studies should re
      address this in larger animal cohorts and determine if fluoxetine treatment is
      associated with adverse treatment effects in individuals with Down syndrome.

PMID- 22848853
TI  - Review of Pharmacological Properties and Chemical Constituents of Pimpinella
      anisum.
AB  - Pimpinella anisum (anise), belonging to Umbelliferae family, is an aromatic plant
      which has been used In Iranian traditional medicine (especially its fruits) as
      carminative, aromatic, disinfectant, and galactagogue. Because the wide
      traditional usage of Pimpinella anisum for treatment of diseases, in this review
      published scientific reports about the composition and pharmacological properties
      of this plant were collected with electronic literature search of GoogleScholar,
      PubMed, Sciencedirect, Scopus, and SID from 1970 to 2011. So far, different
      studies were performed on aniseeds and various properties such as antimicrobial,
      antifungal, antiviral, antioxidant, muscle relaxant, analgesic and anticonvulsant
      activity as well as different effects on gastrointestinal system have been
      reported of aniseeds. It can also reduce morphine dependence and has beneficial
      effects on dysmenorrhea and menopausal hot flashes in women. In diabetic
      patients, aniseeds showed hypoglycemic and hypolipidemic effect and reduce lipid
      peroxidation. The most important compounds of aniseeds essential oil were trans
      anetole, estragole, gamma-hymachalen, para-anisaldehyde and methyl cavicol. Due
      to broad spectrum of pharmacological effects, and very few clinical studies of
      Pimpinella anisum, more clinical trials are recommended to evaluate the
      beneficial effects of this plant in human models and synthesis of new drugs from
      the active ingredients of this plant in future.

PMID- 22848854
TI  - Nonextraction treatment of severe crowding with the aid of corticotomy-assisted
      orthodontics.
AB  - THIS PAPER ILLUSTRATES THE COMBINED NONEXTRACTION ORTHODONTIC TREATMENT WITH THE
      CORTICOTOMY TECHNIQUE IN AN ADULT PATIENT (AGE: 25 years and 3 months) with
      severely crowded arches to accelerate tooth movement and shorten the treatment
      time. Both her upper lateral incisors were congenitally absent and both upper
      central incisors' roots were short. Initial fixed orthodontic appliances
      (bidimensional) were bonded and one week later buccal and lingual corticotomy
      with alveolar augmentation procedure in the maxilla and mandible was performed.
      Orthodontic activation to level and align and unravel the crowding was performed
      every two weeks. The total treatment time was 8 months with no adverse effects
      observed at the end of active treatment. The addition of the decortication
      procedure to the conventional orthodontic therapy decreased the duration of
      treatment significantly. Successful alignment of both arches with ideal overbite
      and overjet as well as adequate occlusion was achieved.

PMID- 22848855
TI  - Q Fever with unusual exposure history: a classic presentation of a commonly
      misdiagnosed disease.
AB  - We describe the case of a man presumptively diagnosed and treated for Rocky
      Mountain spotted fever following exposure to multiple ticks while riding horses.
      The laboratory testing of acute and convalescent serum specimens led to
      laboratory confirmation of acute Q fever as the etiology. This case represents a
      potential tickborne transmission of Coxiella burnetii and highlights the
      importance of considering Q fever as a possible diagnosis following tick
      exposures.

PMID- 22848856
TI  - Occult Breast Cancer due to Multiple Calcified Hamartomas in a Patient with
      Cowden Syndrome.
AB  - Cowden syndrome (CS) is an autosomal dominant disorder characterized by presence
      of multiple hamartomas, and other benign and malignant abnormalities of the
      breasts, skin, thyroid, endometrium, gastrointestinal tract, and central nervous
      system. Hamartomas are benign, developmentally disorganized tumors that can
      develop in any of the above mentioned organs. The presence of massive
      calcifications in the breasts in very young women is an indication to perform a
      breast MRI to exclude a neoplasm since, like in the current case report, presence
      of breast calcifications may obscure a neoplasm. Although fibrocystic disease and
      cooccurrence of fibrocystic disease and breast cancer are much more common than
      CS, the presence of massive calcifications in the breasts of very young women
      should elicit the possibility of an underlying genetic disease. Furthermore,
      breast cancer and macrocephaly are considered major criteria for the diagnosis of
      CS and the combination of both is enough to establish the clinical diagnosis of
      this entity. Fibrocystic disease of the breasts and multinodular goiter are minor
      criteria. Family history is also important for the diagnosis of (any) hereditary
      disease.

PMID- 22848857
TI  - Nephron-sparing surgery for adenocarcinoma in a renal allograft.
AB  - The incidence of malignant tumors in recipients of renal allografts is higher
      than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of
      the tumors in transplanted patients; of them, only 10% are found in transplanted
      kidneys. Transplantectomy has always been the usual treatment. However, during
      the last years, nephron-sparing surgery of the allograft is more frequently done
      in well-selected cases, and therefore dialysis can be avoided. We report the case
      of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm
      tumor in the lower pole of the renal allograft. The patient underwent partial
      nephrectomy successfully. Six years after surgery, there is no evidence of
      recurrence of the disease and the patient maintains an adequate renal function.

PMID- 22848858
TI  - Japanese Alzheimer's disease and other complex disorders diagnosis based on
      mitochondrial SNP haplogroups.
AB  - This paper first explains how the relations between Japanese Alzheimer's disease
      (AD) patients and their mitochondrial SNP frequencies at individual mtDNA
      positions examined using the radial basis function (RBF) network and a method
      based on RBF network predictions and that Japanese AD patients are associated
      with the haplogroups G2a and N9b1. It then describes a method for the initial
      diagnosis of Alzheimer's disease that is based on the mtSNP haplogroups of the AD
      patients. The method examines the relations between someone's mtDNA mutations and
      the mtSNPs of AD patients. As the mtSNP haplogroups thus obtained indicate which
      nucleotides of mtDNA loci are changed in the Alzheimer's patients, a person's
      probability of becoming an AD patient can be predicted by comparing those mtDNA
      mutations with that person's mtDNA mutations. The proposed method can also be
      used to diagnose diseases such as Parkinson's disease and type 2 diabetes and to
      identify people likely to become centenarians.

PMID- 22848859
TI  - Mild cognitive impairment: beyond memory dysfunction.

PMID- 22848860
TI  - Thyroid cancer: molecular aspects and new therapeutic strategies.
AB  - Despite that thyroid cancer accounts for over 90% of tumors that arise from the
      endocrine system, these tumors barely represent 2% of solid tumors in adults.
      Many entities are grouped under the general term of thyroid cancer, and they
      differ in histological features as well as molecular and clinical behavior. Thus,
      the prognosis for patients with thyroid cancer ranges from a survival rate of
      >97% at 5 years, in the case of differentiated thyroid tumors sensitive to
      radioactive iodine, to a 4-month median survival for anaplastic tumors. The high
      vascularity in these tumors and the important role that oncogenic mutations may
      have in the RAS/RAF/MEK pathway and oncogenicity (as suggested by activating
      mutations and rearrangements of the RET gene) have led to the development of
      multitarget inhibitors in different histological subgroups of patients. The
      correct molecular characterization of patients with thyroid cancer is thought to
      be a key aspect for the future clinical management of these patients.

PMID- 22848861
TI  - Subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine
      combination preserves plasma cholesterol, renal antioxidant status, and organ
      weights in rats.
AB  - Recent instances of breakdowns of malaria control programs and the constant
      emergence of drug-resistant parasites to monotherapies have shored up the use of
      artemisinin-based combination therapy (ACT) as the malaria therapy of choice. We
      evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate
      amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats.
      Sixteen albino rats were grouped into three. Group A (n = 5) served as the
      control. Groups B (n = 6) and C (n = 5) were administered, twice daily, oral
      therapeutic doses of artemether-lumefantrine (1.14/6.86 mg/kg/d) and artesunate
      amodiaquine (2.86/8.58 mg/kg/d), respectively, for seven days. From our results,
      ACTs did not significantly (P > 0.05) alter catalase, superoxide dismutase,
      glutathione S-transferase, myeloperoxidase, and total glutathione levels when
      compared with the control. Plasma total cholesterol levels also decreased
      insignificantly (P > 0.05). Organ-system weights were not significantly (P >
      0.05) different from control rats. Artesunate-amodiaquine, but not artemether
      lumefantrine, significantly increased (P < 0.05) lactate dehydrogenase activity
      and also afforded a 27.2% decrease in heart weight when compared with control.
      Also, both ACTs increased (P < 0.05) lipid peroxidation. Overall, artesunate
      amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ
      weights in vivo. However, caution is required above therapeutic indications or in
      chronic doses as this may predispose to renal oxidative stress.

PMID- 22848862
TI  - Retrospective Case-Control Study of Apolipoprotein J/Clusterin Protein Expression
      in Early Liveborn Neonatal Deaths with and without Pontosubicular Necrosis.
AB  - Aims. Our objective was to examine Apo J protein expression in a total of 27
      early liveborn neonatal deaths (less than 7 days of age) selected from the
      Scottish Perinatal Study (gestation of 25-42 weeks) comparing a group with
      histological pontosubicular necrosis (PSN) (n = 12) to a control group lacking
      PSN (n = 15). Methods. Using immunohistochemistry we evaluated postmortem pons
      and hippocampus from patients with PSN versus controls. Results. In the group
      with PSN, 11/12 (92%) cases showed positive Apo J neurones in the
      hippocampus/pons compared with 6/15 (40%) cases without PSN (P = 0.014, odds
      ratio 27.5, 95% confidence interval 2.881-262.48, using exact logistic
      regression)-independent of gestation, presence or absence of clinical asphyxia,
      duration of labour, or postnatal age. Clinical asphyxia was present in 10/15
      (67%) without PSN compared with 11/12 (92%) with PSN. Neuronal Apo J positivity
      was present in 15/21 (71%) of clinically asphyxiated cases compared with 2/6
      (33%) of the cases with no evidence of clinical asphyxia (P = 0.154, odds ratio
      5, 95% confidence interval 0.71 to 34.94). Conclusions. Apo J neuronal protein
      expression is significantly increased in cases with PSN compared to cases without
      PSN-independent of gestation, presence of clinical asphyxia, duration of labour,
      or postnatal age.

PMID- 22848863
TI  - Malignant mixed mullerian tumor: an immunohistochemical study.
AB  - Malignant mixed Mullerian tumor (MMMT) is an uncommon aggressive neoplasm
      composed of both malignant epithelial and mesenchymal components. In this study,
      immunohistochemical stains of germ cell markers, including SALL4, OCT3/4,
      glypican-3, and alpha-fetal protein (AFP), and CDX2 were performed in a series of
      MMMTs. SALL4 nuclear immunoreactivity was detected in 6 out of 19 cases (33%).
      The staining extent ranged from focal to extensive. The staining intensity was
      usually intermediate to strong (the score ranged from 1.5 to 3, and average score
      was 2.3 +/- 0.5 in the positive cases). In addition, glypican-3 cytoplasmic
      reactivity was detected in 14 out of 16 cases (88%) with a mean score of 1.8 +/-
      0.7 (score ranging from 1 to 3). In contrast, OCT3/4 was only positive in 1 out
      of 19 cases and AFP in 2 out of 18 cases (11%). In summary, SALL4 and glypican-3
      were frequently expressed in a subset of MMMTs. Their roles in the pathogenesis
      and biology of MMMT are yet to be determined. MMMT should be included in the
      differential diagnosis when a tumor is positive for SALL4 and/or glypican-3.

PMID- 22848865
TI  - Motor rehabilitation after stroke.

PMID- 22848864
TI  - A Q-Methodology Study of Patients' Subjective Experiences of TIA.
AB  - Background. An expanding body of research has focused on a range of consequences
      of TIA. However, no work has been conducted on the patient's subjective
      experience of TIA. Aim. To capture patients' first-hand experiences of TIA.
      Method. Using Q-methodology which employs both qualitative and quantitative
      approaches, 39 statements relating to the clinical, physical, affective, and
      psychological impact of TIA were distilled from the literature and from patient
      narratives. Consistent with conventional Q-methodology, a purposive sample of
      twentythree post-TIA patients sorted these statements into a normally-distributed
      39-cell grid, according to the extent to which each represented their experience
      of TIA. Results. Casewise factoranalysis was conducted on the sorted statements.
      Eight factors emerged which were labelled: lack of knowledge/awareness of TIA;
      life impact; anxiety; interpersonal impact; depression; physical consequences;
      cognitive avoidance/denial; constructive optimism. Conclusions. Five of the eight
      factors confirmed existing research on the impact of TIA, but three new issues
      emerged: deep-seated anxiety, denial and constructive optimism. The emerging
      perspectives highlight areas to target in the management of TIA and could inform
      health education messages, patient information, individualised caremanagement,
      and enhancement of coping strategies. With development, the findings could be
      used as a basis for psychometric risk assessment of TIA patients.

PMID- 22848866
TI  - Intravenous thrombolytic treatment in the oldest old.
AB  - Background and Purpose. Intravenous thrombolysis using tissue plasminogen
      activator is safe and probably effective in patients >80 years old. Nevertheless,
      its safety has not been specifically addressed for the oldest old patients (>=85
      years old, OO). We assessed the safety and effectiveness of thrombolysis in this
      group of age. Methods. A prospective registry of patients treated with
      intravenous thrombolysis. Patients were divided in two groups (<85 years and the
      OO). Demographic data, stroke aetiology and baseline National Institute Health
      Stroke Scale (NIHSS) score were recorded. The primary outcome measures were the
      percentage of symptomatic intracranial haemorrhage (SICH) and functional outcome
      at 3 months (modified Rankin Scale, mRS). Results. A total of 1,505 patients were
      registered. 106 patients were OO [median 88, range 85-101]. Female sex,
      hypertension, elevated blood pressure at admission, cardioembolic strokes and
      higher basal NIHSS score were more frequent in the OO. SICH transformation rates
      were similar (3.1% versus 3.7%, P = 1.00). The probability of independence at 3
      months (mRS 0-2) was lower in the OO (40.2% versus 58.7%, P = 0.001) but not
      after adjustment for confounding factors (adjusted OR, 0.82; 95% CI, 0.50 to
      1.37; P = 0.455). Three-month mortality was higher in the OO (28.0% versus 11.5%,
      P < 0.001). Conclusion. Intravenous thrombolysis for stroke in OO patients did
      not increase the risk of SICH although mortality was higher in this group.

PMID- 22848867
TI  - Ultrasound determination of gestational age using placental thickness in female
      dogs: an experimental study.
AB  - Objective. To verify if the placental thickness allows determining the
      gestational age, evaluating the correlation between the referred gestational age
      with the studied one, and the accuracy of the placental thickness measurement
      (biometry) with fetal morphologic parameters in bitches. Methods. The placental
      thickness of 336 bitches of diverse breeds was evaluated. Bitches were divided in
      three groups by body weight: small, medium, and big large size. The gestations
      pregnancies were evaluated by ultrasound from the third week of gestation. An
      analysis was performed between the mean values of the gestational age obtained of
      placental thickness by adjustment of curves and the reported gestational age.
      Student's t-test was applied to compare the mean of reported and placental
      thickness gestational age. Significance was defined as P < 0.05. Results. A
      positive and statistically significant correlation exists between the placental
      thickness and gestational age. The expression that presents the best correlation
      coefficient and explanation was thickness of placenta = 0.021x gestational age 
      0.314. Conclusion. It is possible to determine the gestational age in relation to
      the placental thickness measured by ultrasound in bitches with a satisfactory
      accuracy in relation to fetal morphologic parameters as gestational vesicle,
      ribs, or kidneys.

PMID- 22848868
TI  - Tuberculosis in humans and cattle in jigawa state, Nigeria: risk factors
      analysis.
AB  - A cross-sectional study was conducted from September 2008 to March 2009 to
      identify risk factors for BTB in cattle and humans in Jigawa State, Nigeria. A
      total of 855 cattle belonging to 17 households were subjected to comparative
      intradermal tuberculin test (CITT) while interviewer-administered questionnaire
      was used to obtains information on the risk factors. Twenty-two (22) respondent
      (5%) amongst the families sampled had TB or clinical signs suggestive of TB,
      while 9 (2%) had reactor cattle in their herds; However, no statistically
      significant association (P >= 0.05) was observed between reactor cattle and human
      TB cases in the households. The habit of milk and meat consumption was found to
      be affected by occupation and location of the household residence. None of these
      risk factors (food consumption, living with livestock in the same house, and
      presence of BTB-positive cattle) were found to be statistically significant.

PMID- 22848870
TI  - The use of amberlite adsorbents for green chromatography determination of
      volatile organic compounds in air.
AB  - Passive samplers have been widely used for volatile organic compounds
      determination. Following the green chemistry tendency of the direct determination
      of adsorbed compounds in membrane-based devices through using head space direct
      chromatography analysis, this work has evaluated the use of Amberlite XAD-2, XAD
      4, and XAD-16 adsorbents as a filling material for passive samplers. Direct
      analysis of the membranes by HS-GC-MS involves a solvent-free method avoiding any
      sample treatment. For exposed membranes, recoveries ranged from 10% to 203%,
      depending on the compound and adsorbent used. The limit of the detection values
      ranged from 1 to 140 ng per sampler. Acceptable precision and sensitivity levels
      were obtained for the XAD resins assayed.

PMID- 22848869
TI  - Progress in Oral Vaccination against Tuberculosis in Its Main Wildlife Reservoir
      in Iberia, the Eurasian Wild Boar.
AB  - Eurasian wild boar (Sus scrofa) is the main wildlife reservoir for tuberculosis
      (TB) in Iberia. This review summarizes the current knowledge on wild boar
      vaccination including aspects of bait design, delivery and field deployment
      success; wild boar response to vaccination with Bacillus Calmette-Guerin (BCG)
      and inactivated Mycobacterium bovis; and wild boar vaccination biosafety issues
      as well as prospects on future research. Oral vaccination with BCG in captive
      wild boar has shown to be safe with significant levels of protection against
      challenge with virulent M. bovis. An oral vaccination with a new heat-killed M.
      bovis vaccine conferred a protection similar to BCG. The study of host-pathogen
      interactions identified biomarkers of resistance/susceptibility to tuberculosis
      in wild boar such as complement component 3 (C3) and methylmalonyl coenzyme A
      mutase (MUT) that were used for vaccine development. Finally, specific delivery
      systems were developed for bait-containing vaccines to target different age
      groups. Ongoing research includes laboratory experiments combining live and heat
      killed vaccines and the first field trial for TB control in wild boar.

PMID- 22848872
TI  - The splicing mutant of the human tumor suppressor protein DFNA5 induces
      programmed cell death when expressed in the yeast Saccharomyces cerevisiae.
AB  - DFNA5 was first identified as a gene responsible for autosomal dominant deafness.
      Different mutations were found, but they all resulted in exon 8 skipping during
      splicing and premature termination of the protein. Later, it became clear that
      the protein also has a tumor suppression function and that it can induce
      apoptosis. Epigenetic silencing of the DFNA5 gene is associated with different
      types of cancers, including gastric and colorectal cancers as well as breast
      tumors. We introduced the wild-type and mutant DFNA5 allele in the yeast
      Saccharomyces cerevisiae. The expression of the wild-type protein was well
      tolerated by the yeast cells, although the protein was subject of degradation and
      often deposited in distinct foci when cells entered the diauxic shift. In
      contrast, cells had problems to cope with mutant DFNA5 and despite an apparent
      compensatory reduction in expression levels, the mutant protein still triggered a
      marked growth defect, which in part can be ascribed to its interaction with
      mitochondria. Consistently, cells with mutant DFNA5 displayed significantly
      increased levels of ROS and signs of programmed cell death. The latter occurred
      independently of the yeast caspase, Mca1, but involved the mitochondrial fission
      protein, Fis1, the voltage-dependent anion channel protein, Por1 and the
      mitochondrial adenine nucleotide translocators, Aac1 and Aac3. Recent data
      proposed DFNA5 toxicity to be associated to a globular domain encoded by exon 2
      6. We confirmed these data by showing that expression of solely this domain
      confers a strong growth phenotype. In addition, we identified a point mutant in
      this domain that completely abrogated its cytotoxicity in yeast as well as human
      Human Embryonic Kidney 293T cells (HEK293T). Combined, our data underscore that
      the yeast system offers a valuable tool to further dissect the apoptotic
      properties of DFNA5.

PMID- 22848871
TI  - How does ionizing irradiation contribute to the induction of anti-tumor immunity?
AB  - Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack
      tumors. It induces a stop of cancer cell proliferation and finally leads to tumor
      cell death. During the last years it has become more and more evident that
      besides a timely and locally restricted radiation-induced immune suppression, a
      specific immune activation against the tumor and its metastases is achievable by
      rendering the tumor cells visible for immune attack. The immune system is
      involved in tumor control and we here outline how RT induces anti-inflammation
      when applied in low doses and contributes in higher doses to the induction of
      anti-tumor immunity. We especially focus on how local irradiation induces
      abscopal effects. The latter are partly mediated by a systemic activation of the
      immune system against the individual tumor cells. Dendritic cells are the key
      players in the initiation and regulation of adaptive anti-tumor immune responses.
      They have to take up tumor antigens and consecutively present tumor peptides in
      the presence of appropriate co-stimulation. We review how combinations of RT with
      further immune stimulators such as AnnexinA5 and hyperthermia foster the
      dendritic cell-mediated induction of anti-tumor immune responses and present
      reasonable combination schemes of standard tumor therapies with immune therapies.
      It can be concluded that RT leads to targeted killing of the tumor cells and
      additionally induces non-targeted systemic immune effects. Multimodal tumor
      treatments should therefore tend to induce immunogenic tumor cell death forms
      within a tumor microenvironment that stimulates immune cells.

PMID- 22848874
TI  - On crestal/marginal bone loss around dental implants.

PMID- 22848873
TI  - On widening the stream.

PMID- 22848875
TI  - Biological aging of implant surfaces and their restoration with ultraviolet light
      treatment: a novel understanding of osseointegration.
AB  - The topographic and physicochemical features of implant surfaces influence the
      process of osseointegration. The biologic properties of implant surfaces have
      been considered to remain stable over time, ie, the capability of
      osseointegration of implant surfaces presumably does not change over time after
      manufacturing. However, recent reports have demonstrated that titanium surfaces
      undergo a progressive change in their biologic characteristics over time,
      resulting in a significant decrease in osseointegration capability. In comparison
      to newly prepared titanium surfaces, 4-week-old titanium surfaces (ie, stored for
      4 weeks after processing) required more than twice as much healing time to
      achieve a similar strength of osseointegration. The boneimplant contact
      percentage for the 4-week-old surfaces was less than 60%, as opposed to more than
      90% for the new surfaces. In vitro, the 4-week-old surfaces showed only 20% to
      50% of the levels of recruitment, attachment, settlement, and proliferation of
      osteogenic cells versus new surfaces. On the other hand, a series of recent
      papers reported the generation of highly cell-attractive and osteoconductive
      titanium surfaces by ultraviolet (UV) light treatment. The phenomenon, defined as
      photofunctionalization, caused a fourfold acceleration in the process of
      osseointegration and resulted in nearly 100% bone-implant contact. Remarkably
      enhanced behavior and response of osteogenic cells around UV-treated surfaces
      exceeded the levels observed for the newly prepared surfaces. These studies
      indicated that UV treatment reverses the time-dependent biologic degradation of
      titanium and even enhances the surface beyond its innate potential. The present
      paper summarizes the findings about the aging-like time-dependent biologic
      degradation of titanium surfaces as well as about the discovery of UV
      photofunctionalization as a solution for this phenomenon. It also provides a
      novel understanding of osseointegration and calls for immediate attention to a
      new avenue of exploration in the science and therapeutics of implant dentistry.

PMID- 22848876
TI  - Comparison of point-of-care methods for preparation of platelet concentrate
      (platelet-rich plasma).
AB  - PURPOSE: This study analyzed the concentrations of platelets and growth factors
      in platelet-rich plasma (PRP), which are likely to depend on the method used for
      its production. MATERIALS AND METHODS: The cellular composition and growth factor
      content of platelet concentrates (platelet-rich plasma) produced by six different
      procedures were quantitatively analyzed and compared. Platelet and leukocyte
      counts were determined on an automatic cell counter, and analysis of growth
      factors was performed using enzyme-linked immunosorbent assay. RESULTS: The
      principal differences between the analyzed PRP production methods (blood bank
      method of intermittent flow centrifuge system/platelet apheresis and by the five
      point-of-care methods) and the resulting platelet concentrates were evaluated
      with regard to resulting platelet, leukocyte, and growth factor levels. The
      platelet counts in both whole blood and PRP were generally higher in women than
      in men; no differences were observed with regard to age. Statistical analysis of
      platelet-derived growth factor AB (PDGF-AB) and transforming growth factor beta1
      (TGF-beta1) showed no differences with regard to age or gender. Platelet counts
      and TGF-beta1 concentration correlated closely, as did platelet counts and PDGF
      AB levels. There were only rare correlations between leukocyte counts and PDGF-AB
      levels, but comparison of leukocyte counts and PDGF-AB levels demonstrated
      certain parallel tendencies. CONCLUSIONS: TGF-beta1 levels derive in substantial
      part from platelets and emphasize the role of leukocytes, in addition to that of
      platelets, as a source of growth factors in PRP. All methods of producing PRP
      showed high variability in platelet counts and growth factor levels. The highest
      growth factor levels were found in the PRP prepared using the Platelet
      Concentrate Collection System manufactured by Biomet 3i.

PMID- 22848877
TI  - Three-dimensional evaluation of bone changes following ridge preservation
      procedures.
AB  - PURPOSE: To evaluate three-dimensionally the bone change following ridge
      preservation procedures (RPP) using computed tomography (CT). MATERIALS AND
      METHODS: Subjects in need of implant therapy were enrolled in the study. The
      teeth were extracted, and sockets underwent RPP with a bioactive glass (Inion
      BioRestore, Inion Oy). The patients were scanned with CT within 1 week and 3
      months after surgery. Horizontal and vertical radiographic measurements were
      performed on superimposed CT scans to evaluate bone changes in the alveolar sites
      during the 3-month period. RESULTS: Thirteen subjects participated, and 32 teeth
      were extracted and treated with grafting. Alveolar sites treated with RPP
      demonstrated a preservation of about 77% of the original width dimensions, with a
      mean loss of 1.8 +/- 1.1 mm in width. Moreover, it was observed that the vertical
      loss of buccal bone was 2.7 +/- 1.1 mm, while the loss of lingual bone was 1.9 +/
      1.2 mm. CONCLUSIONS: The CT evaluation was helpful to assess that the bone loss
      in width was less than the vertical bone loss of both walls 3 months after RPP.

PMID- 22848878
TI  - Alkali and heat treatment of titanium implant material for bioactivity.
AB  - PURPOSE: This study was conducted to evaluate alkali- and heat-treated titanium
      implant material. MATERIALS AND METHODS: Ninety-eight square plates of
      commercially pure titanium were divided into three groups. Group 1 plates were
      left untreated, and groups 2 and 3 were subjected to anodization and alkali
      treatment for 24 and 48 hours, respectively. Treated specimens were then
      subdivided into three equal subgroups (a, b, and c), which were heat treated for
      1 hour at temperatures of 500 degrees C, 700 degrees C, and 800 degrees C,
      respectively. Changes in the crystalline structure were analyzed using x-ray
      diffractometry. Surface roughness was measured using a surface roughness tester.
      Selected specimens were immersed in a specially prepared simulated body fluid for
      10 days. Calcium and phosphorous deposition on the specimens was detected using
      energy dispersive x-ray analysis. RESULTS: Increasing the alkali treatment period
      and heat treatment temperature positively affected surface roughness and
      formation of a bioactive sodium titanium oxide (sodium titanate) layer on the
      titanium surface, especially after heat treatment at 800 degrees C. There was a
      significantly higher calcium deposition on specimens of group 3 in comparison
      with those of groups 1 and 2. The results of pH and ion concentration changes of
      the used simulated body fluid confirmed the results of energy dispersive x-ray
      analysis. CONCLUSION: Alkali and heat treatment of titanium implant materials
      created better treatment conditions for obtaining a bioactive implant material.

PMID- 22848879
TI  - Zirconia implant abutments: microstructural analysis.
AB  - PURPOSE: Yttria-stabilized zirconia (ZrO2-Y2O3) ceramics have received increasing
      attention in recent years because of their stress-induced tetragonal-to
      monoclinic (martensitic) transformation. This unique process acts as a toughening
      mechanism, imparting strength and toughness to the ceramic alloy. This property,
      along with well-documented biocompatibility, is now being exploited in an
      increasing number of medical applications, including implant dentistry. To
      prevent clinical problems and predict their behavior and physical limitations, a
      characterization of the ceramic elements used in dental restorations is
      essential. The aim of the present study is to characterize the crystal structure,
      elemental composition, and micr ostructure of asreceived ZiReal Post (Biomet 3i)
      zirconium oxide abutments, as well as specimens coated with a first layer of a
      low-fusing fluoroapatite ceramic. MATERIALS AND METHODS: Zirconium oxide
      abutments, both as-received and porcelain-coated, were studied using the
      following techniques: x-ray diffraction, x-ray fluorescence, energy dispersive x
      ray spectroscopy, optical microscopy, and scanning and transmission electron
      microscopy. RESULTS: X-ray analyses detected only the presence of Zr, O, Y, and
      hafnium (Hf), in an amount of 3% to 4% molecular weight Y2O3-ZrO2. X-ray
      diffraction measurements showed that the ceramic abutment crystallizes mainly in
      the tetragonal phase, with some residual monoclinic phase. The microstructure is
      characterized by a rather homogenous grain distribution, formed by equiaxed and
      fine grains with a mean size of 0.30 MUm. CONCLUSIONS: Compositional and
      diffraction results are consistent with polycrystalline yttria-stabilized
      tetragonal zirconia. The material is susceptible to undergoing the stress-induced
      transformation toughening mechanism because of the very fine grain size. Except
      for machining ring marks, the surfaces exhibit an excellent finishing quality. No
      structural modifications were observed in the fluoroapatite ceramic-coated
      abutments because of the relatively low temperatures used for ceramization
      compared with the phase transformation temperatures used for zirconia.

PMID- 22848880
TI  - Influence of methodologic aspects on the results of implant-abutment interface
      microleakage tests: a critical review of in vitro studies.
AB  - PURPOSE: This study sought to evaluate the influence of methodologic aspects on
      variations in the findings of in vitro microleakage studies of the implant
      abutment interface. MATERIALS AND METHODS: The MEDLINE, EMBASE, and Cochrane
      Library databases were consulted for in vitro studies published between 1990 and
      August 2011. Date from the studies that met the inclusion and exclusion criteria
      were arranged in tables and subjected to descriptive analysis. RESULTS: Twenty
      one studies were found to be eligible for the analysis after application of the
      inclusion/exclusion criteria. Sixteen studies used bacteria (76.2%), one used a
      bacterial toxin (4.76%), one used saliva (4.76%), two employed dyes (9.52%), and
      one used a combination of dyes and bacteria (4.76%). Eight studies evaluated
      microleakage from the inner portion of the implant to the external portion
      (38.1%) and nine examined the reverse (42.85%), while four studies investigated
      the relationship between them (19.05%). The volume inoculated inside the implants
      ranged from 0.1 to 5.0 mL. The bacterial concentrations used in the tests ranged
      from 2.41 x 106 to 8 x 108 colony-forming units/mL. Oral bacterial flora;
      mixtures of bacteria, toluidine blue, and gentian violet; and lipopolysaccharide
      of Salmonella enterica bacterial toxins were used. The monitoring period of test
      results ranged from 24 hours to 11 weeks for bacteria, 5 minutes to 7 days for
      dye, and 7 days for bacterial toxins. In four studies, microleakage was
      correlated with the size of the implant-abutment microgap. The external-hexagon
      implant configuration showed the greatest microleakage, followed by internal
      trilobe, internal-hexagon, and internal-taper configurations. CONCLUSION: The
      lack of standardization hinderd comparisons of the studies and could explain the
      divergent results. It is suggested for future studies that special emphasis be
      placed upon inoculation and analysis of the specific volume for each system,
      lower concentrations of inoculated bacterial suspensions, and shorter follow-up
      time when using bacteria.

PMID- 22848881
TI  - Surface alterations of several dental materials by a novel ultrasonic scaler tip.
AB  - PURPOSE: To assess the effects of a recently developed ultrasonic scaler tip,
      composed mainly of copper, on the surfaces of several dental materials. MATERIALS
      AND METHODS: Representative samples of dental materials, including titanium, type
      II gold, cobalt-chromium alloy, zirconia, and porcelain, were prepared. Three
      ultrasonic scaler tips of conventional metal (CM), carbon composite (CC), and
      copper alloy (CA) were prepared. To simulate ultrasonic scaling in an oral
      environment, 30 g of force was applied using a double-pan balance, and the scaler
      tip was allowed to move horizontally 5 mm for three consecutive cycles of 20
      seconds each. The power of the scaler tip was set to intermediate according to
      the manufacturer's advice. The surface morphology of each dental material was
      examined using scanning electron microscopy and confocal laser scanning
      microscopy. Statistical analysis was performed through one-way analysis of
      variance and post hoc Scheffe test. All values were considered significant when P
      < .05. RESULTS: Surface alterations of titanium, type II gold, and cobalt
      chromium alloy by the CM tip were much greater than those caused by the CC and CA
      tips. No alterations were created on the zirconia surface by the CM, CC, or CA
      tips. On the porcelain surface, surface roughness (Ra) induced by the CM tip was
      1.86 and 1.72 times higher than that produced by the CC and CA tips, respectively
      (P < .001). CONCLUSIONS: Within the limitations of this study, the surface
      alterations induced by CC and CA tips on the surfaces of dental materials were
      comparable. Therefore, this novel ultrasonic copper alloy scaler tip may possibly
      be used for the maintenance of implant prostheses.

PMID- 22848882
TI  - Microbial community composition on modified dental implant surfaces: an in vivo
      study.
AB  - PURPOSE: The aim of the present in vivo study was to examine alterations of the
      microbial community structure in biofilms on different dental implant surfaces
      over the time. MATERIALS AND METHODS: Zirconium nitride-coated glass (ZrN-glass)
      and ZrN-coated polished titanium (ZrN-Ti) disks were used as substrates and
      polished titanium (Ti-pol) was used as a control. The specimens were mounted on
      removable intraoral splints in one adult. After 24 hours and 14 days of intraoral
      exposure, the microbial biofilms were analyzed by generating 16S rRNA gene clone
      libraries. RESULTS: ZrN coating of a Ti surface altered the microbial composition
      early on (24 hours), with a tendency to augment Lactobacillus-related phylotypes
      later. Long-term exposure (14 days) of dental implant surfaces to microbes
      resulted in a significantly different composition of the biofilm on all three
      tested surfaces. CONCLUSIONS: This preliminary study showed that a ZrN-Ti disk
      surface harbors a significantly different microbial composition from a polished
      Ti surface. Further improvement of ZrN physical vapor deposition coatings might
      help to influence the adhesion of bacteria that are less pathogenic, thereby
      reducing the risk of peri-implantitis.

PMID- 22848883
TI  - The effect of screw length on fracture load and abutment strain in dental
      implants with external abutment connections.
AB  - PURPOSE: One of the most common types of failure in dental implants is fracture
      of the abutment screw, after which the remnant is usually not easily removed. The
      purpose of this study was to investigate the effect of abutment screw length on
      the amount of screw resistance load and strain after loading. MATERIALS AND
      METHODS: Twenty-one implants and straight abutments were prepared. The implants
      were placed in acrylic resin blocks at an angle of 30 degrees relative to the
      long axis. The abutment screws were prepared and classified into seven groups
      based on length (n = 3 abutments per group). The implants and abutments were
      joined with a torque of 30 Ncm. Strain gauges were attached to the abutments, and
      the implant-abutment assemblies were compressed. Curves of strain over time, peak
      load, and load at fracture were measured. Linear models of the variables over the
      abutment screw length were analyzed. RESULTS: The break and peak loads were
      significantly associated with abutment screw length. However, all measured break
      and peak loads were greater than the maximal occlusal force. There were no
      significant changes in peak or break strain values associated with screw length
      (P > .05). CONCLUSIONS: Clinically, fractured abutment screws may be replaced by
      shorter abutment screws without removal of the broken screw remnant.

PMID- 22848884
TI  - An in vitro model to evaluate the accuracy of guided surgery systems.
AB  - PURPOSE: An in vitro model was developed and tested to evaluate the precision of
      guided implant systems. The accuracy of dental implants placed with a flapless
      technique was analyzed using a stereolithographic template in vitro. Differences
      between the virtual and actual positions of the implants were measured. MATERIALS
      AND METHODS: Six polyurethane mandibles with artificial silicone gums were
      fabricated, and each was fitted with an individual computed tomography (CT)
      guide. Stereolithographic guides were created using computer-aided
      design/computer-assisted manufacturing technology and virtual planning software.
      All stereolithographic guides had four holes for stabilization pins and three
      holes for cylindric implants. After implant placement, the mandibles were
      subjected to another CT scan to compare the actual implant positions with the
      planned positions. The pre- and postimplantation CT images were superimposed
      using digital processing image software to evaluate the linear and angular
      deviations between the virtual planning data and the surgical results. RESULTS:
      The mean angular discrepancy between the virtual and actual positions of the 18
      placed implants was 2.16 +/- 0.92 degrees. Among the placed implants, 66.7% were
      situated a mean of 0.38 +/- 0.03 mm apical to the planned vertical position, and
      33.3% were situated 0.39 +/- 0.03 mm coronal to the planned position.
      CONCLUSIONS: Within the limitations of the present study, this tool showed
      promising accuracy in virtual implant placement.

PMID- 22848885
TI  - An in vitro comparison of joint stability of implant-supported fixed prosthetic
      suprastructures retained with different prosthetic screws and levels of fit under
      masticatory simulation conditions.
AB  - PURPOSE: This study sought to determine an optimal postinsertion retorque
      protocol to maintain implantsuprastructure joint stability after being subjected
      to a 1-year in vitro masticatory simulation. MATERIALS AND METHODS: Ten
      mandibular implant-supported dentures were manufactured and 20 epoxy resin models
      were obtained for two fit levels: passive fit and misfit. Eight groups (n = 20)
      were created on the basis of vertical fit (passive or misfit) and prosthetic
      screw material (titanium or gold). The single-screw test was performed and the
      vertical misfit was quantified using an optical microscope. Loosening torque was
      measured after simulations of two types of clinical use: (1) 6 months of use,
      torque loosening, retightening, another 6 months of use, and loosening torque;
      and (2) 1 year of use followed by loosening torque. Data were analyzed by means
      of two-way analysis of variance and the Tukey test. RESULTS: The factors of
      cycling time and condition use (fit level and screw type), as well the
      interaction between these factors, significantly influenced the loosening torque
      (P < .05). After 6 months and another 6 months of clinical use simulation,
      titanium screws showed higher loosening torque values than did gold screws for
      the same fit level (P < .05). After 1 year of clinical use simulation, titanium
      and gold screws in passively fit dentures showed higher loosening torque values
      than they did in misfit dentures (P < .05). The titanium screws presented a
      decrease in the loosening torque after 1 year in misfit dentures. CONCLUSIONS:
      The stability of titanium screws was higher than that of gold screws after 6
      months of simulation because of their lower plastic deformation. When the cycling
      time was analyzed, titanium screws were less stable after 1 year of simulation
      because of loss of torque in the presence of misfit.

PMID- 22848886
TI  - Influence of preparation mode and depth on the fracture strength of zirconia
      ceramic abutments restored with lithium disilicate crowns.
AB  - PURPOSE: Zirconia implant abutments offer enhanced esthetics and promote biologic
      sealing; however, the effect of laboratory or intraoral preparation on the
      mechanical stability of zirconia has not been investigated. The purpose of the
      study was to evaluate the influence of the preparation mode and depth on the
      fracture strength of zirconia abutments restored with lithium disilicate crowns.
      MATERIALS AND METHODS: To replace a maxillary central incisor (11.0 mm in height
      and 8.0 mm in width), 35 lithium disilicate crowns were cemented onto zirconia
      abutments on 4.5-  degrees  - 15-mm titanium implants. Lithium disilicate implant
      crowns were divided into five study groups (n = 7) according to the abutment
      preparation mode (milling by the manufacturer or milling by the Celay System
      [Mikrona] [P]) and preparation depth (0.5 mm [A], 0.7 mm [B], or 0.9 mm [C]). All
      groups were subjected to quasi-static loading (S) at 135 degrees to the implant
      axis in a universal testing machine. RESULTS: Mean fracture strengths were: group
      SA, 384 +/- 84 N (control); group SB, 294 +/- 95 N; group SPB, 332 +/- 80 N;
      group SC, 332 +/- 52; group SPC, 381 +/- 101 N. All specimens presented a typical
      fracture mode within the implant/abutment internal connection. Multiple
      regression analysis revealed that preparation depth up to 0.7 mm statistically
      influenced the fracture strength (P = .034), whereas the preparation mode did not
      seem to play an important role (P = .175). CONCLUSION: Regardless of preparation
      mode, circumferential preparation of zirconia abutments might negatively affect
      the fracture strength of adhesively cemented single implant lithium disilicate
      crowns.

PMID- 22848887
TI  - The effect of enamel matrix derivative on spreading, proliferation, and
      differentiation of osteoblasts cultured on zirconia.
AB  - PURPOSE: This study investigated the effect of enamel matrix derivative (EMD) on
      spreading, proliferation, and differentiation of osteoblasts cultured on zirconia
      disks with smooth and rough surfaces. MATERIALS AND METHODS: EMD was added to the
      culture medium or coated on zirconia disks that had machined (smooth) or
      sandblasted (rough) surfaces. The effects of EMD on cell proliferation of MC3T3
      E1 osteoblastic cells were examined using a hemocytometer. Osteoblastic
      differentiation was examined by histologic analysis of alkaline phosphatase (ALP)
      activity and the degree of mineralization. ALP activity was also measured
      quantitatively. Scanning electron microscopic analysis was performed to observe
      cell morphology. Enzyme-linked immunosorbent assay of osteocalcin and reverse
      transcriptase polymerase chain reaction of osteocalcin, osteopontin, and type 1
      collagen were performed to investigate the expression of osteoblast-related
      genes. RESULTS: The addition of EMD to the medium enhanced the spreading,
      proliferation, and differentiation of osteoblasts cultured on zirconia. However,
      when it was coated on zirconia, EMD reduced osteoblastic spreading and adhesion
      in the early stage of culture, although it enhanced proliferation and
      differentiation of osteoblasts in later stages. A promotive effect of EMD on
      osteocalcin mRNA expression, mineralization, and ALP activity of osteoblasts
      cultured on the rough surface was observed. CONCLUSIONS: EMD may contribute to
      treatment with zirconia implants via its promotion of osteoblastic proliferation
      and activity. However, the procedure for application of EMD may be a crucial
      factor for the outcome of implants.

PMID- 22848888
TI  - Cement application techniques in luting implant-supported crowns: a quantitative
      and qualitative survey.
AB  - PURPOSE: To investigate different techniques used by dentists when luting an
      implant-supported crown and to evaluate the application of cement quantitatively
      and qualitatively. MATERIALS AND METHODS: Participants were given a bag
      containing cement sachet, mixing pad, spatula, a variety of application
      instruments, and a polycarbonate crown form. The participants were instructed
      with a standardized audio-video presentation to proportion the cement, mix it,
      and apply it to the intaglio of the crown as they would if they were to cement it
      onto an implant abutment in a clinical situation. The crowns were weighed, first
      unfilled and then again once the applied cement had set. The mean weights of
      fully-loaded crowns (n = 10) were used as a control group. The patterns of cement
      loading were recorded. The weights of collected cement-loaded crowns were
      compared to those of the control group and analyzed statistically. RESULTS: Four
      hundred and one dentists in several different geographic locations were surveyed.
      Three distinct cement loading patterns were observed: gross application (GA),
      brush-on application (BA), and margin application (MA). The mean weights for each
      cement loading pattern were 242.2 mg for the GA group, 59.9 mg for the BA group,
      and 59.0 mg for the MA group. The weight of cement in the GA group was
      significantly higher than that in the other groups. No statistically significant
      difference between groups BA and MA was seen. CONCLUSIONS: The diversity of the
      cement loading patterns disclosed in this study indicates that there is a lack of
      uniformity and precision in methods and a lack of consensus in the dental
      community regarding the appropriate quantity of cement and placement method for a
      cement-retained implant crown.

PMID- 22848889
TI  - Quality assessment of prospective case series of dental implant surgery and
      prosthodontics published between 2004 and 2008: a systematic review.
AB  - PURPOSE: The aim of this systematic review was to assess the methodologic and
      statistical quality of prospective case series of treatment interventions of
      dental implant surgery and prosthodontics published between 2004 and 2008.
      MATERIALS AND METHODS: Prospective case series were identified following detailed
      searches of the Medline, EMBASE, and CINAHL databases. Identified studies were
      independently assessed by two nonblinded reviewers for 10 key methodologic and
      statistical domains. Information was collected using a customized data collection
      sheet. RESULTS: The initial search yielded 1,484 studies. Following application
      of inclusion criteria, 31 prospective case series reports that did not present
      the same patient material were identified for this review. Interexaminer
      agreement was assessed for all domains (median kappa score, 0.84). All
      disagreements were resolved by discussion. The source of funding was unclear in
      20 studies (65%). Treatment protocol was adequately described in 21 studies
      (68%), and eligibility criteria were adequately reported in 24 studies (77%).
      Only two studies (6.5%) tested the intraexaminer/interexaminer reliability of at
      least one outcome of interest. Inferential statistical analysis was presented in
      21 studies. However, this analysis was only considered appropriate in 12 studies
      (57%). Confidence intervals were reported in four studies (13%). CONCLUSIONS:
      Prospective case series of treatment interventions of dental implant surgery and
      Prosthodontics are poorly analyzed and rarely test the reliability of outcome
      measures. These particular studies have limited external validity and appear to
      provide little unbiased evidence to support clinical decision-making.

PMID- 22848890
TI  - Assessment of potential orthodontic mini-implant insertion sites based on
      anatomical hard tissue parameters: a systematic review.
AB  - PURPOSE: To estimate the applicability of potential sites for insertion of
      orthodontic mini-implants (OMIs) by a systematic review of studies that used
      computed tomography (CT) or cone beam CT to evaluate anatomical bone quality and
      quantity parameters, such as bone thickness, available space, and bone density.
      MATERIALS AND METHODS: Medline and the Cochrane Database of Systematic Reviews
      were searched to identify all relevant papers. Several key words were used, such
      as computerized/computed tomography, mini-implants, and OMIs. The anatomical
      variables that were assigned in each article to a specific site suggesting it as
      the ideal or best alternative were assessed separately and evaluated with a
      scoring system. RESULTS: Twenty-two articles were included in the study. The most
      favorable areas for OMI insertion in the maxilla are proposed between the first
      and second molars buccally and palatally. The best area in the mandible is also
      between the first and second molars, both buccally and lingually. In the palate,
      the paramedian area 3 to 6 mm posterior to and 2 to 9 mm lateral to the incisive
      foramen was identified as the best site for OMI placement. CONCLUSIONS: Despite
      the heterogeneity of the studies, there was considerable agreement regarding the
      optimal site for OMI insertion among most studies that investigated anatomical
      hard tissue parameters based on CT or CBCT data. In this respect, the posterior
      area from the second premolar to the second molar is the best option for OMI
      placement in alveolar bone.

PMID- 22848891
TI  - Correlation between dental implant insertion torque and mandibular alveolar bone
      density in osteopenic and osteoporotic subjects.
AB  - PURPOSE: Osteoporotic patients require particular attention during implant
      placement, and insertion torque (IT) has been established as a simple and
      noninvasive method to assess local bone quality and primary implant stability.
      This study aimed to test the hypothesis that IT was not significantly correlated
      with bone density, as assessed with computed tomography, in a group of osteopenic
      and osteoporotic patients. In addition, the hypothesis that IT was not
      significantly correlated with implant length was tested. MATERIALS AND METHODS:
      Fifty-three completely edentulous patients with compromised bone mineral density
      (osteoporotic or osteopenic) who required treatment with complete maxillary
      dentures and complete mandibular implantsupported overdentures participated in
      the study. Each patient received two screw-shaped self-tapping implants
      (Branemark Mark III TiUnite) at the mandibular canine regions. The IT of each
      implant during placement was recorded. The Pearson correlation between IT and
      implant site bone density (Hounsfield unit) obtained from presurgical computed
      tomographic scans was analyzed. The relationship between IT and implant length
      was also studied. RESULTS: IT was significantly correlated to implant site bone
      density but not to implant length. CONCLUSION: IT can be a viable and practical
      means to assess mandibular bone quality in patients with compromised general bone
      density.

PMID- 22848892
TI  - Biomechanical implant treatment complications: a systematic review of clinical
      studies of implants with at least 1 year of functional loading.
AB  - PURPOSE: The aim of this article is to discuss the current literature available
      on the etiology and management of biomechanical complications of dental implant
      treatment. MATERIALS AND METHODS: An electronic search of the PubMed database for
      English-language articles published before May 31, 2011, was performed based on a
      focus question: "How can biomechanical implant treatment complications be managed
      and identified?" The key words used were "dental implant," "etiology,"
      "management," "excessive occlusal forces," "occlusal forces," "occlusion,"
      "parafunctional habits," "biomechanical failure," "biomechanical complications,"
      and "occlusal overloading." Clinical trials with a minimum of 10 implants
      followed for at least 1 year after functional loading were included. RESULTS: The
      initial electronic search identified 2,087 publications, most of which were
      eliminated, as they were animal studies, finite element analyses, bench-top
      studies, case reports, and literature reviews. After the titles, abstracts, and
      full text of 39 potentially eligible publications were reviewed, 15 studies were
      found to fulfill the inclusion criteria. CONCLUSION: Occlusal overloading was
      thought to be the primary etiologic factor in biomechanical implant treatment
      complications, which commonly included marginal bone loss, fracture of
      resin/ceramic veneers and porcelain, retention device or denture base fracture of
      implant-supported overdentures, loosening or fracture of abutment screws, and
      even implant failure. Occlusal overloading was positively associated with
      parafunctional habits such as bruxism. An appreciation of the intricacy of
      implant occlusion would allow clinicians to take a more preventive approach when
      performing implant treatment planning, as avoidance of implant overloading helps
      to ensure the long-term stability of implant-supported prostheses.

PMID- 22848893
TI  - The buccal fat pad flap: an option to prevent and treat complications regarding
      complex zygomatic implant surgery. Preliminary report.
AB  - PURPOSE: To evaluate the use of the buccal fat pad flap (BFPF) technique as an
      option to prevent complications in the treatment of patients with atrophic
      maxillae rehabilitated after complex zygomatic implant surgery. MATERIALS AND
      METHODS: A retrospective study was made of completely edentulous patients
      submitted to zygomatic implant surgery between May 2005 and November 2007.
      Patients with severely atrophic maxillae received conventional and zygomatic
      implants and were followed after the implants were loaded. Preoperative
      evaluation included panoramic radiography and computed tomographic scans of the
      maxilla to identify the anatomic conditions and presence of pathology. RESULTS:
      Eight male patients with a mean age of 57 years and atrophic maxillae were
      rehabilitated with zygomatic implants placed using the BFPF technique. The BFPF
      technique was used in complex situations, including oroantral communication
      associated sites, areas that had lost the sinus wall, and extrasinus implant
      placement. A total of 16 conventional implants, 4 long (21-mm) tilted implants,
      and 22 zygomatic implants was placed. The patients were rehabilitated with fixed
      prostheses and were followed for a minimum of 15 months. None of the conventional
      implants failed and none of the zygomatic implants failed or presented with soft
      tissue complications. CONCLUSION: The BFPF presented a high success rate,
      demonstrating that it is a viable and predictable treatment option to prevent and
      treat soft tissue complications in complex zygomatic implant surgery.

PMID- 22848894
TI  - Clinical evaluation of satisfaction in patients rehabilitated with an immediately
      loaded implant-supported prosthesis: a controlled prospective study.
AB  - PURPOSE: The purpose of this controlled prospective study was to compare the
      satisfaction of patients rehabilitated with an immediately loaded implant
      supported prosthesis and patients rehabilitated with a conventional denture in
      the mandible. MATERIALS AND METHODS: Selected mandibular partially or totally
      edentulous patients were included in this prospective study. Patients' mandibles
      were completely rehabilitated with immediately loaded implants supporting a screw
      retained full-arch prosthesis (test group) or with a conventional denture
      (control group). The Satisfaction Profile (SAT-P), which investigates a number of
      psychologic aspects related to the function and esthetics of the stomatognathic
      apparatus, was administered to each patient 1 month before and 3 months after
      provisional prosthetic rehabilitation. The questionnaire comprised four different
      SAT-P items: quality of eating, eating behavior, mood, and self-confidence. A
      visual analog scale was used to elicit patient responses. SAT-P item scores were
      analyzed statistically by means of the Student t test and the chi-square test (or
      the Mann-Whitney nonparametric test), with P < .05 considered significant.
      RESULTS: Forty-one patients were consecutively treated with 205 immediately
      loaded implants supporting a screw-retained full-arch prosthesis (test group); 38
      patients were consecutively treated with a conventional denture (control group).
      Statistically significant differences were observed between the test and control
      groups for all four SAT-P items. The test group reported greater satisfaction for
      all items versus the control group. In both groups, the differences between pre-
      and postrehabilitation values were statistically significant. CONCLUSIONS: Each
      patient was satisfied with their treatment outcomes, but patients who received an
      implant-supported prosthesis were more satisfied than the patients who received a
      conventional denture. The results suggest that a screw-retained full-arch
      prosthesis on immediately loaded implants is a predictable means of enhancing
      patient satisfaction.

PMID- 22848895
TI  - The use of a piezoelectric ultrasonic osteotome for internal sinus elevation: a
      retrospective analysis of clinical results.
AB  - PURPOSE: To explore the possibility and evaluate the clinical outcome of
      accomplishing maxillary internal sinus floor augmentation through the use of a
      piezoelectric osteotome in conjunction with dental implant placement and to
      discuss this technique. MATERIALS AND METHODS: Patients attending the outpatient
      clinic of the Department of Dental Implantology, Hospital of Stomatology, Tongji
      University, between July 2007 and September 2009, who had insufficient bone
      volume to harbor endosseous implants at least 8 mm long in the lateral/posterior
      maxilla because of sinus pneumatization were enrolled in the study. Sinus
      augmentations were accomplished with a piezoelectric osteotome, followed by
      implant placement, either immediately or delayed (6 months after augmentation, if
      the residual ridge height was less than 4 mm). RESULTS: Thirty patients with 36
      maxillary molar sites with insufficient alveolar bone height as a result of
      pneumatization of the sinus were included in this study. The residual vertical
      bone height ranged from 2 to 8 mm. Twenty-eight implants were placed into 24
      patients immediately after sinus augmentation. Another eight implants were placed
      into 6 patients 6 months after sinus augmentation. Only one sinus membrane
      perforated (failure rate: 2.78%). Only one implant was lost during the
      observation period. No other implant mobility or rapid bone loss was seen during
      a follow-up period of 5 to 27 months. CONCLUSIONS: Application of a piezoelectric
      osteotome for internal sinus elevation simplified manipulation of the membrane
      and greatly reduced the chance of perforation. The pressure gradient between
      sinus and implant cavity was helpful in accomplishing this technique.

PMID- 22848896
TI  - Inward-inclined implant platform for the amplified platform-switching concept: 18
      month follow-up report of a prospective randomized matched-pair controlled trial.
AB  - PURPOSE: This prospective randomized matched-pair controlled trial aimed to
      evaluate marginal bone levels and soft tissue alterations at implants restored
      according to the platform-switching concept with a new inward-inclined platform
      and compare them with external-hexagon implants. MATERIALS AND METHODS:
      Traditional external-hexagon (control group) implants and inward-inclined
      platform implants (test group), all with the same implant body geometry and 13 mm
      in length, were inserted in a standardized manner in the posterior maxillae of 40
      patients. Radiographic bone levels were measured by two independent examiners
      after 6, 12, and 18 months of prosthetic loading. Buccal soft tissue height was
      measured at the time of abutment connection and 18 months later. RESULTS: After
      18 months of loading, all 80 implants were clinically osseointegrated in the 40
      participating patients. Radiographic evaluation showed mean bone losses of 0.5 +/
      0.1 mm (range, 0.3 to 0.7 mm) and 1.6 +/- 0.3 mm (range, 1.1 to 2.2 mm) for test
      and control implants, respectively. Soft tissue height showed a significant mean
      decrease of 2.4 mm in the control group, compared to 0.6 mm around the test
      implants. CONCLUSIONS: After 18 months, significantly greater bone loss was
      observed at implants restored according to the conventional external-hexagon
      protocol compared to the platform-switching concept. In addition, decreased soft
      tissue height was associated with the external-hexagon implants versus the
      platform-switched implants.

PMID- 22848897
TI  - Clinical outcomes of single dental implants with external connections: results
      after 2 to 13 years.
AB  - PURPOSE: The aim of this retrospective study was to evaluate the long-term
      survival rates and the frequency of complications associated with single implants
      and their associated restorations. MATERIALS AND METHODS: A retrospective cohort
      study was performed in patients who received dental implants between 1997 and
      2007. The cohort included patients who had a single implant restored with a
      cemented or screwed restoration that had been in function for more than 2 years.
      The cumulative implant survival rates and peri-implant conditions (marginal bone
      loss, pocket depth, and plaque, gingival, and bleeding indices), as well as
      prosthodontic maintenance requirements, were evaluated. Descriptive statistics,
      the chi-square test, and regression models were used. RESULTS: Seventy-three
      implants were placed in 44 patients (32 women, 12 men; mean age, 48 years). All
      implants were available for follow-up after 2 to 13 years (mean follow-up, 60
      months). The overall cumulative 5-year survival rates for implants were 95.9%,
      and most of the prostheses (98.6%) remained functional throughout the observation
      period. The overall frequency of complications was 29.6% (4.3% inflammatory,
      22.5% prosthetic, 2.8% operative). The average peri-implant marginal bone loss
      was 1.8 mm. Peri-implant soft tissue conditions such as plaque and bleeding
      indices and pocket depths were also satisfactory. However, the presence of
      inflammation was significantly associated with pocket depth and gingival
      keratinized mucosa. The need to retighten loose abutment screws (21%) was the
      most frequent prosthodontic maintenance performed. However, all loose abutment
      screws occurred in prostheses retained with titanium screws, and 92.9% of the
      prostheses had a UCLA-type abutment. CONCLUSION: The implants and the associated
      prosthetic constructions used in this study showed excellent survival rates.
      However, there was a high frequency of prosthetic complications associated with
      titanium screws and UCLA cast abutments. Other prosthetic components may have
      yielded different results.

PMID- 22848898
TI  - A randomized controlled clinical trial comparing the effects of three loading
      protocols on dental implant stability.
AB  - PURPOSE: The primary goal of this stratified randomized controlled trial (SRCT)
      was to compare the stability of dental implants placed under three different
      loading regimens during the first 16 weeks of healing following implant
      placement. Implants were loaded immediately, early (6 weeks), or with
      conventional/delayed timing (12 weeks). Secondary outcomes were to compare
      marginal bone adaptation for 3 years after placement. MATERIALS AND METHODS:
      Single posterior implant sites in the maxilla or mandible were examined. The
      insertion torque value was the primary determinant of load assignment. Resonance
      frequency analysis was performed at follow-up appointments for the first 16 weeks
      (with results provided as implant stability quotients [ISQs]). Marginal bone
      levels were assessed via radiographs. RESULTS: Forty patients each received a
      single 4.0-mm diameter dental implant between 2004 and 2007. One implant failure
      occurred in Lekholm and Zarb type 4 bone with insertion torque value (ITV) of <
      8.1 Ncm; the cumulative success rate was 97.5%. All implants, when classified by
      bone and loading type, increased in stability over time, with a minor reduction
      of 1.3 ISQ units seen at 4 weeks in the immediate loading group. The mean
      marginal bone loss over 3 years was 0.22 mm. The mean ITVs at implant placement
      for bone types 1 and 2 (grouped together), 3, and 4 were 32, 17, and 10,
      respectively, and were significantly different (P < .05). CONCLUSIONS: ITV was a
      good objective measure of bone type. Using an ITV of 20 Ncm as the determinant
      for immediate loading and an ITV of 10 Ncm or greater as the determinant for
      early loading provided long-term success for this implant and led to no negative
      changes in tissue response. All bone type groups and loading groups showed no
      reduction in stability during the first 4 months of healing.

PMID- 22848899
TI  - Peri-implant bone remodeling around an extraction socket: predictions of bone
      maintenance by finite element method.
AB  - PURPOSE: The aim of this study was to investigate peri-implant bone remodeling as
      a response to biomechanical factors, including implant size and contour,
      magnitude of occlusal load, and properties of osteogenic bone grafts through the
      use of a computational algorithm. MATERIALS AND METHODS: A bone-remodeling
      algorithm was incorporated into the finite element method, where bone remodeling
      takes place as a result of the biomechanical alteration caused by dental implant
      placement and continues until the difference between the homeostatic state and
      the altered state is minimized. The site-specific homeostatic state was based on
      a model consisting of a natural tooth. Three long (11-mm) implants and two short
      (5-mm) implants were investigated. A three-dimensional segment of the mandible
      was constructed from a computed tomographic image of the premolar region, and an
      extraction socket was filled with bone graft. RESULTS: Generally, the extent of
      bone loss in the cortical region was greater and denser bone developed at both
      the implant crest and apex with increased occlusal loads. The areas between
      implant threads were prone to bone resorption. Bone graft materials that were
      relatively stiff and that had high equilibrium stimulus values appeared to cause
      increased bone loss. CONCLUSIONS: Short implants are better for conserving the
      mechanotransductive signaling environment of the natural tooth than long
      implants. Also, short implants are predicted to lead to less interfacial bone
      loss at high loads over the long term, while long implants are associated with a
      more consistent level of bone loss for different amounts of loading. It is also
      predicted that in the long term, bone grafts with relatively low elastic modulus
      lead to lower levels of interfacial bone loss.

PMID- 22848900
TI  - Biomechanical effect of a zirconia dental implant-crown system: a three
      dimensional finite element analysis.
AB  - PURPOSE: The objective of this study was to analyze and compare the stresses in
      two different bone-implant interface conditions in anisotropic three-dimensional
      finite element models (FEMs) of an osseointegrated implant of either commercially
      pure titanium or yttrium-partially stabilized zirconia (Y-PSZ) in combination
      with different superstructures (gold alloy or Y-PSZ crown) in the posterior
      maxilla. MATERIALS AND METHODS: Three-dimensional FEMs were created of a first
      molar section of the maxilla into which was embedded an implant, connected to an
      abutment and superstructure, using commercial software. Two versions of the FEM
      were constructed; these allowed varying assignment of properties (either a bonded
      and or a contact interface), so that all experimental variables could be
      investigated in eight groups. Compact and cancellous bone were modeled as fully
      orthotropic and transversely isotropic, respectively. Oblique (200-N vertical and
      40-N horizontal) occlusal loading was applied at the central and distal fossae of
      the crown. RESULTS: Maximum von Mises and compressive stresses in the compact
      bone in the two interfaces were lower in the zirconia implant groups than in the
      titanium implant groups. A similar pattern of stress distribution in cancellous
      bone was observed, not only on the palatal side of the platform but also in the
      apical area of both types of implants. CONCLUSION: The biomechanical parameters
      of the new zirconia implant generated a performance similar to that of the
      titanium implant in terms of displacement, stresses on the implant, and the bone
      implant interface; therefore, it may be a viable alternative, especially for
      esthetic regions.

PMID- 22848901
TI  - Shedding light on the laser wavelength effect in Raman analysis of skin
      epidermises.
AB  - Confocal Raman microspectroscopy is a promising technique which enables measuring
      the molecular composition of the skin layers, non-destructively and without
      extrinsic markers. The Raman approach is increasingly used in skin research but
      with various experimental conditions. In addition to the different skin types,
      one of the varying parameters is the wavelength of laser excitation. This
      parameter contributes strongly in the skin Raman response. The present work aimed
      to evaluate this effect for 3 different wavelengths, 532, 633 and 785 nm, on pig
      ear skin models. The Raman signal was assessed in the spectral fingerprint
      region. According to the Raman response for stability, repeatability, variability
      and fluorescence contribution, the 785 nm excitation wavelength was shown to be
      the most suitable for epidermis depth profiling in the fingerprint region.

PMID- 22848902
TI  - [How should German statutory health insurance-accredited physicians handle non
      covered individual health services? Deficits and recommendations from patients'
      point of view].
AB  - BACKGROUND AND OBJECTIVE: German statutory health insurance-registered physicians
      increasingly offer individual health services (IHS). Within a mixed methods
      study, focus groups were conducted to describe deficits and recommendations from
      patients' point of view about how physicians should handle IHS. PATIENTS AND
      METHODS: Seven semi-structured focus groups (alltogether 50 participants) were
      conducted, stratified for region, gender and school education and homogenised for
      age and health status. The discussions were recorded, transcribed and content
      analysed (thematic coding). RESULTS: Across all focus groups patients wished in
      depth advise, neutral information, transparent dissociation of IHS from services
      of statutory health insurances (SHI), appropriate time for consideration and
      information, consultations for a second opinion and transparent billing of all
      medical services. There was no consensus about who should initiate IHS and who
      should develop and disseminate information on IHS. Members of SHI wish for
      information on SHI services and transparent information developed by neutral
      parties. DISCUSSION: The handling of IHS needs to be regulated urgently. Based on
      the integration of quantitative and qualitative data we infer patient-centred
      conclusions and recommendations for SHI-accredited physicians.

PMID- 22848904
TI  - The impact of the time interval between two successive deliveries in an obstetric
      unit in terms of the mode of each delivery and the rate of perinatal mortality.
AB  - OBJECTIVE: To analyze the relationship of the time interval between two
      deliveries, done by one obstetric team, on the delivery mode of the subsequent
      birth; to define the length of this interval; and to evaluate this time interval
      as a risk factor for increased perinatal mortality in a population-based cohort.
      METHODS: All singleton deliveries at >= 24 weeks' gestation in Lower Saxony,
      Germany, between 2001 and 2005 (a total of 317,663 deliveries including 402 cases
      of perinatal mortality) were analyzed. The mode of the previous and the
      subsequent delivery, the time interval between the two deliveries, the time of
      birth, the hospital volume, and the existence of an affiliated neonatal ward were
      investigated. RESULTS: When the first vaginal delivery was <45 min, there was a
      reduced probability that the subsequent birth would be a cesarean section. In
      case of a previous cesarean section, the cesarean rate of the following birth was
      influenced up to 165 min. In a multivariate analysis, vaginal deliveries
      following an earlier vaginal birth and occurring within <45 min were associated
      with increased perinatal mortality. Repeated cesarean sections within <165 min
      were associated with increased perinatal mortality when occurring at night or on
      weekends. CONCLUSION: A short time interval between two deliveries in an
      obstetric unit constitutes an independent risk factor for perinatal mortality.

PMID- 22848903
TI  - Mitochondrial dynamics in heart failure.
AB  - Mitochondria have been widely studied for their critical role in cellular
      metabolism, energy production, and cell death. New developments in research on
      mitochondria derived from studies in yeast have led to the discovery of entirely
      new mitochondrial processes that have implications for mitochondrial function in
      heart failure. Recent studies have identified that maintaining normal
      mitochondrial morphology and function depends on the dynamic balance of
      mitochondrial fusion and fission (division). Mitochondrial fusion and fission are
      constant ongoing processes, which are essential for the maintenance of normal
      mitochondrial function. Studies in heart failure have been limited but suggest a
      possible reduction in mitochondrial fusion. As mitochondrial fusion and fission
      have important links to apoptosis, a key mechanism of loss of cardiac myocytes in
      heart failure, there are many implications for both heart failure research and
      treatment.

PMID- 22848905
TI  - WAPM Working Group on Nutrition: potential chronobiotic role of human milk in
      sleep regulation.
AB  - BACKGROUND: Organization of the sleep states and a normal sleep pattern in the
      neonatal period and early infancy is essential for brain development and
      plasticity. The establishment of a consolidated circadian sleep-wake cycle occurs
      between 1 and 4 months of life in term infants. This period may be even longer
      for preterm infants who are exposed to relentless interventions in neonatal
      intensive care units. The sleep should be respected and protected. OBJECTIVE AND
      METHODS: Human milk (HM) contains bioactive sleep-promoting components, and
      recent evidence shows that some of these components show circadian oscillations.
      This article reviews the existing evidence regarding the role of these HM
      components on sleep. This topic is prefaced with a brief information about the
      basic concepts concerning sleep. Consecutively, chronobiotic and chrononutrition
      concepts are introduced. RESULTS: Melatonin, tryptophan, nucleosides/nucleotides,
      and vitamin B12 are components of HM that have sleep-promoting characteristics.
      The sleep-inducing effects of these components are well-established in animal and
      adult human studies. Interestingly, melatonin, tryptophan, and 5'-adenosine
      monophosphate and 5'-guanosine monophosphate nucleotides in HM have been shown to
      exhibit also circadian oscillations. Although 5'-uridine monophosphate does not
      have a circadian rhythm, its levels increase during the night. CONCLUSION: HM has
      a potential to function as a "synchronizer," helping the infant to consolidate a
      circadian sleep-wake cycle, thanks to its several bioactive components with
      chronobiotic characteristics. Research is warranted to address gaps in this
      field, such as the association between the circadian oscillations of the sleep
      promoting factors in HM and the quantity/quality of infant sleep.

PMID- 22848906
TI  - What is in a name?

PMID- 22848907
TI  - New ICD-10-CM system requires greater specificity in nuclear medicine
      documentation.

PMID- 22848909
TI  - ICANL report.

PMID- 22848908
TI  - Message from the president.

PMID- 22848910
TI  - Directory of accredited nuclear medicine technology programs.

PMID- 22848911
TI  - NCOR report.

PMID- 22848912
TI  - Keeping it simple.
AB  - Recently I got a lift home with a friend, who is a keen skier. Her kids were in
      the back seat and her 5-year-old son announced abruptly that he knew every town
      from Castlemaine to Mount Hotham, and would I like to hear them? I marvelled as
      he proceeded carefully through the list, starting with Harcourt and ending with
      Harrietville and Hotham Village. A few times he paused briefly as he assembled
      the image of the main street of each town in his mind. My friend laughed, 'Do you
      think we've been to the snow too many times?!'

PMID- 22848913
TI  - HIV--a cause of pyrexia of unknown origin.

PMID- 22848914
TI  - Cardiac stress testing.

PMID- 22848915
TI  - Feeding in the first year of life.

PMID- 22848916
TI  - Referrals to A&E--changes over 5 years.
AB  - In July 2008, using 2003 to 2007 data from BEACH (Bettering the Evaluation and
      Care of Health), we published an article in this journal about patients attending
      general practice who were referred to hospital accident and emergency departments
      (A&E).(1) The precise referral rate at that time was 1.85 per 1000 encounters
      (95% CI: 1.70-1.99). A new analysis using recent data shows that in 2008 to 2011
      the general practice referral rate to A&E was significantly higher: 2.70 per 1000
      encounters (95% CI: 2.48-2.92).

PMID- 22848917
TI  - [Histoplasmosis in Latin America].

PMID- 22848918
TI  - When the self is contested ground.

PMID- 22848919
TI  - Strings attached.

PMID- 22848920
TI  - [Report of the European Respiratory Society 2007 Congress].

PMID- 22848921
TI  - Case study. The disasters of March 11th. Commentary.

PMID- 22848922
TI  - Case study. The disasters of March 11th. Commentary.

PMID- 22848923
TI  - Case study. The disasters of March 11th. Commentary.

PMID- 22848924
TI  - [Restructuring the medical system].

PMID- 22848925
TI  - [Forefront of the clinic and research of pulmonary MAC disease].

PMID- 22848926
TI  - Evaluation of serum resistin levels in periodontal health and disease and effects
      of non surgical periodontal therapy on its levels.
AB  - BACKGROUND: Resistin and adiponectin are the adipokines secreted by adipocytes
      and various inflammatory cells. These adipokines are known to play an important
      role in insulin resistance. The aim of this study was to determine the serum
      resistin levels in periodontal health and disease and also, to determine the
      effect of nonsurgical periodontal therapy on its levels. METHODS: A total of 40
      patients (20 Males and 20 Females; age range 20-50 years) participated in the
      study. Subjects were categorized as healthy (group 1; Controls) and chronic
      periodontitis (group 2; Study) groups based on their periodontal status.
      Periodontal parameters (Plaque index (PI), Gingival index (GI), Bleeding index
      (BI), Probing pocket depth (PPD), Clinical attachment loss (CAL)) together with
      serum resistin levels were assessed at baseline and between 6-8 weeks following
      nonsurgical periodontal therapy for subjects in group 2 and only at baseline in
      group 1. Sera were tested in duplicate (single run), and the results were
      averaged. RESULTS: Study group showed higher (1.89 +/- 1.83 ng/ml) serum resistin
      levels, compared to control group (1.35 +/- 0.70 ng/ml). However, this difference
      was not statistically significant (P = 0.227). Also, resistin levels decreased
      following nonsurgical periodontal therapy but, this decrease failed to show any
      statistical significance, with pretreatment levels being 1.89 +/- 1.83 ng/ml and
      post treatment levels being 1.59 +/- 1.01 ng/ml (P = 0.386). CONCLUSION:
      Observations of the present study revealed that there was not much difference in
      the serum resistin levels between the cases and the controls. Also the decrease
      in the resistin levels following nonsurgical periodontal therapy did not show any
      statistical significance.

PMID- 22848927
TI  - [Russian scientific and practical conference "Complex aproaches to
      standartization of diagnostic and therapy of mental disorders"].

PMID- 22848928
TI  - Going vertical. Dignity's play for U.S. HealthWorks illustrates push for
      integrated care.

PMID- 22848930
TI  - Held responsible.

PMID- 22848929
TI  - 'Larger is better'.

PMID- 22848931
TI  - Suspense for AHLA. Despite late news, reform law a popular subject.

PMID- 22848932
TI  - More than they bargained for. IRS guidance on tax-exempt rules too prescriptive,
      hospitals say.

PMID- 22848934
TI  - Chasing history. A glimpse inside the newsroom.

PMID- 22848933
TI  - Cost control is key: HFMA.

PMID- 22848935
TI  - Achieving more with wireless. California's El Camino Hospital uses built-in
      infrastructure and a variety of technologies to improve quality of care, patient
      experience.

PMID- 22848936
TI  - Caring about culture.

PMID- 22848937
TI  - Maintaining skin integrity bariatric patients.
AB  - The skin is the largest organ in the body, accounting for 16% of total body
      weight. Individuals who are obese face particular dermatological challenges, and
      health professionals working in the community setting should be alert to these
      risks. Skin assessment should be undertaken by a competent practitioner within a
      holistic framework. If assessment and treatment is not undertaken in a timely
      manner there is risk of tissue damage with associated cost and care implications.
      This article discusses aspects of skin care that apply particularly to bariatric
      patients, and draws on best practice guidance from the literature to help nurses
      ensure that the patient is appropriately managed in relation to their skin care,
      wound treatment and body dynamics.

PMID- 22848939
TI  - Getting the patient's perspective helps improve outcomes.

PMID- 22848938
TI  - Leading service improvement in changing times.
AB  - Leadership within community nursing needs to be embraced and red to ensure it is
      inherent within the profession, not just adopted by a few. As healthcare
      organisations continue to change and develop to meet new political agendas,
      meeting the needs of patients and associated improvements to service will be
      shaped by those who are willing to take ideas forward. This article looks at ways
      all community nurses can develop their leadership skills in order to affect
      change.

PMID- 22848940
TI  - Community supports used by older people post hospital discharge.
AB  - Community support in the post-discharge period is of importance, as difficulties
      managing at home can lead to readmission to hospital (Strunin et. al, 2007;
      Arbaje et al, 2009). There is evidence that support from family in the community
      is perceived to be the best option by older people (McCann and Evans 2002;
      Themessl-Huber et. al, 2007). However, during the transition from hospital to
      home gaps may occur in the continuity of support, with the potential for poor
      outcomes. Knowledge about how older people interact with supports in their
      communities is therefore important to inform health and social care policy and
      provision. This article presents the results of a southern Irish study to examine
      the use of informal and formal supports and services by older people in the post
      discharge period. Recommendations for practice and further research are included.

PMID- 22848941
TI  - Meeting the needs of patients with chronic pain.

PMID- 22848942
TI  - Timely symptom management at end of life using 'just in case' boxes.
AB  - This article discusses the successful implementation of anticipatory prescribing
      using 'just in case' boxes (JICB) in primary care across the Grampian region and
      a subsequent follow up survey one year later. The implementation approach used
      local educational sessions to primary care clinicians. The survey was distributed
      to 65 primary care bases to gauge awareness and use of the JICB and thoughts
      about how the box was used. An estimate of prescription costs was undertaken
      using stock balance forms. The response rate was 89%. All respondents had heard
      about the JICB and most had used a JICB. There were 37 positive comments about
      the benefits to patients, 15 comments about the process and 11 negative comments,
      often about possible drug wastage. The cost of a prescription was estimated at
      pounds 22.12. The findings have informed our ongoing educational programme and
      build on the strong links that exist between primary care and the specialist
      palliative care service.

PMID- 22848944
TI  - Antimicrobial resistance needs action.

PMID- 22848943
TI  - Consent to care: assessing patient decision-making capacity.
AB  - Decision-making capacity has been described as the 'key to autonomy'. A person
      who is capable of making a decision about their health care must have that
      decision respected by a district nurse, as to proceed against the person's wishes
      would amount to the tort of trespass to the person and, in some cases, a criminal
      assault. It is essential, therefore, that district nurses are able to assess the
      decision-making capacity of their patients.

PMID- 22848945
TI  - Training bodies need nurse representation.

PMID- 22848946
TI  - Campaign to improve fundamental care wins backing from across U.K.

PMID- 22848947
TI  - Nurse education needs could be sidelined by new training boards.

PMID- 22848948
TI  - Nurses prepare for extra workload during doctors' day of action.

PMID- 22848949
TI  - Research reveals lack of financial support for top-up qualifications.

PMID- 22848950
TI  - Nursing initiative aims to deliver improvements despite the cuts.

PMID- 22848951
TI  - Be a guiding light.
AB  - Stephen Wright launches a four-part series on leadership by considering the
      qualities that make an inspirational clinical leader. Those at ease with
      themselves reconcile the qualities of head and heart, hard and soft, and are
      adept at making the system work for patients.

PMID- 22848952
TI  - 'This house believes that caring can and should be measured'.
AB  - The case for and against the measurement of care is explored by four nursing
      academics. Supporters of the idea say measurement is essential so that nurses can
      benchmark improvements and gain a better insight into the quality of care. Their
      opponents say caring is a 'moral art' or so 'irredeemably vague' it is futile to
      try measuring it.

PMID- 22848953
TI  - A champion idea?
AB  - The Scottish government aims to have 300 dementia champions in place by 2013. The
      champions--to be drawn from health and social, care staff--undergo training to
      enable them to lead improvements in care. The scheme has its critics, but
      supporters insist that champions are making a big difference to patient care.

PMID- 22848954
TI  - Educational responses to unethical healthcare practice.
AB  - The aim of this article is to explore explanations for unethical healthcare
      practice and identify educational responses. The meaning of unethical practice is
      outlined and causes of it are suggested, primarily relating to individual
      perpetrators and organisational culture or climate. Empirical and theoretical
      literature is reviewed and research findings are discussed. Individual resilience
      and the ethical climate of healthcare organisations are considered as responses
      to unethical practice. Role modelling is explored, acknowledging the role of
      effective leadership.

PMID- 22848955
TI  - Importance of hand hygiene during invasive procedures.
AB  - Invasive devices, such as urinary catheters and peripheral and central venous
      catheters, can form part of essential patient care and may provide life-saving
      support and treatment. However, the invasive nature of these devices and the
      vulnerability of patients can increase the risk of acquiring a healthcare
      associated infection (HCAI). This article highlights the importance of best
      practice in relation to insertion and management of invasive devices,
      incorporating hand hygiene, to reduce the risk of HCAI. Although the information
      can be applied to invasive devices in general, the focus is on urinary catheters.

PMID- 22848956
TI  - Optimising palliative and end of life care in hospital.
AB  - The acute hospital setting is increasingly regarded as an important area for the
      delivery of palliative care. A significant number of patients with advanced, life
      limiting illness have a range of palliative care needs, some of which can be met
      by ward staff, but others may require additional, specialist input. Several
      factors have the potential to limit the palliative care patients in hospital
      receive, not least of these being disagreement about when and how the transition
      to palliative care should take place. In practice, however, palliative care can
      readily be delivered in conjunction with active disease management.

PMID- 22848957
TI  - Liver transplantation.

PMID- 22848958
TI  - Equality control.

PMID- 22848959
TI  - Work in progress.

PMID- 22848960
TI  - Failure is an option.

PMID- 22848961
TI  - Performance-related pay proposals to be explored at national meeting.

PMID- 22848962
TI  - Trust transforms ward culture after adopting Care campaign.

PMID- 22848963
TI  - Changes to regulatory framework could raise registrants' fees further.

PMID- 22848964
TI  - Hospital staff are urged to act on signs of patient deterioration.

PMID- 22848965
TI  - Greater support for clinicians will improve care, RCN fellows agree.

PMID- 22848966
TI  - From heart failure to success.
AB  - A cardiovascular disease service in Merseyside is keeping patients out of
      hospital and providing them with faster and more effective care. The key to the
      service's success is the integration of formerly fragmented services. The model
      is popular with nurses, who no longer work in isolation and are supported to
      provide holistic care.

PMID- 22848967
TI  - Why spirituality is essential for nurses.
AB  - This article presents the case for 'engaged spirituality' as the key to improving
      nurses' ability to cope under pressure and remain compassionate towards patients.
      The authors argue that it is not a luxury addition to care, but just as important
      as skills and resources. A seven-point manifesto for spirituality in nursing sets
      out the place for spirituality in health care, and calls for changes in education
      and training to allow all nurses to see themselves and patients as one.

PMID- 22848968
TI  - No place like home.
AB  - Employers nursing experts accept the need to care for more people in their own
      homes, avoiding inappropriate and expensive hospital admissions. But the
      investment needed to make this happen safely is lacking.

PMID- 22848969
TI  - Identifying, analysing and solving problems in practice.
AB  - When a problem is identified in practice, it is important to clarify exactly what
      it is and establish the cause before seeking a solution. This solution-seeking
      process should include input from those directly involved in the problematic
      situation, to enable individuals to contribute their perspective, appreciate why
      any change in practice is necessary and what will be achieved by the change. This
      article describes some approaches to identifying and analysing problems in
      practice so that effective solutions can be devised. It includes a case study and
      examples of how the Five Whys analysis, fishbone diagram, problem tree analysis,
      and Seven-S Model can be used to analyse a problem.

PMID- 22848970
TI  - Acne vulgaris in patients with skin of colour: special considerations.
AB  - There is a paucity of nursing literature in the UK about the management of skin
      diseases in patients with skin of colour. Acne vulgaris is a common condition
      affecting all skin types. However, there may be histological and clinical
      differences in patients with skin of colour. This article describes the
      management of acne in patients with skin of colour, including potential sequelae
      that may be triggered by the condition and its treatment. The aetiology of acne
      will be briefly outlined and management of mild, moderate and severe forms of the
      condition wiII be discussed, highlighting considerations and subtleties when
      prescribing.

PMID- 22848971
TI  - Travellers' diarrhoea: causes, prevention and treatment.
AB  - This article describes the prevention and treatment of travellers' diarrhoea, the
      leading cause of illness in people travelling abroad. The most common cause of
      travellers' diarrhoea worldwide is bacterial pathogens, which account for up to
      80% of cases. Exercising caution over dietary selection and personal hygiene is
      the most common method used for reducing the risk of acquiring travellers'
      diarrhoea. Antibiotics, probiotics, prebiotics and bismuth subsalicylate have all
      been indicated for the prevention of this distressing condition. Treatments
      include antimotility agents, oral rehydration salts and antibiotics.

PMID- 22848973
TI  - Working the magic.

PMID- 22848974
TI  - Communicate with clarity.

PMID- 22848972
TI  - Breast cancer.

PMID- 22848975
TI  - Things can only get better.

PMID- 22848977
TI  - Utilization of a massive transfusion protocol during liver lobe resection: a case
      report.
AB  - The literature shows substantial data that acute coagulopathy and hemorrhage
      without rigorous resuscitative efforts has a high morbidity and mortality. The
      utilization of protocols for a massive transfusion and resuscitation can lead to
      improved outcomes in morbidity and mortality. Protocols for massive transfusion
      allow for improved access to blood components and delivery systems, improved
      timing of administration, and a transfusion ratio of red blood cells to fresh
      frozen plasma and to platelets that has been shown to decrease the overall
      transfusion requirements. Research and evidence from the armed services has shown
      remarkable improvements in morbidity and mortality when a massive transfusion
      protocol is implemented in the care of traumatically injured soldiers. The use
      and continued review of these military data appear to have a substantial impact
      on how the civilian healthcare system addresses massive transfusion and
      resuscitation in the critically injured and hemorrhagic patient.

PMID- 22848976
TI  - Methylene blue to treat vasoplegia due to a severe protamine reaction: a case
      report.
AB  - Protamine sulfate is used during coronary artery bypass graft surgery to reverse
      the anticoagulating effects of heparin. Vasoplegic syndrome is a state of
      endothelial dysregulation that produces profound vasodilatation that is
      refractory to vasopressors. This syndrome leads to systemic hypoperfusion and may
      progress to death. Up to 27% of patients after cardiac bypass may experience
      vasoplegia. Symptoms of vasoplegia may also be present in many different clinical
      settings. This case report describes a 57-year-old woman who after cardiac bypass
      experienced a severe protamine reaction with profound hypotension, which was
      unresponsive to volume resuscitation and vasopressor therapy. A dramatic increase
      in blood pressure resulted almost immediately after administration of methylene
      blue. This patient had no prior risk factors for a protamine reaction other than
      her current cardiac surgery. A review of the pathophysiologic characteristics
      associated with vasoplegia and the pharmacodynamics of methylene blue will
      potentially enable anesthesia providers to utilize this lifesaving drug when
      needed.

PMID- 22848978
TI  - Implementation of an evidence-based extubation checklist to reduce extubation
      failure in patients with trauma: a pilot study.
AB  - This prospective, case-controlled observational study assessed whether an
      evidence-based extubation checklist would increase anesthesia providers'
      documentation of standardized extubation criteria and reduce the occurrence of
      preventable extubation failures in the early postoperative period. The sample
      consisted of 622 ASA Physical Status I to IV patients, aged 10 to 100 years but
      primarily adults, who underwent elective and emergency surgeries at a university
      based adult trauma teaching hospital. Before the study, all anesthesia and
      postanesthesia care unit staff received an in-service on adherence to an evidence
      based extubation checklist, followed by implementation of the checklist for 12
      weeks. Demographic data, anesthesia flow sheets, provider notes, and quality
      assurance records were reviewed to determine utilization of the checklist before
      extubation and to ascertain those patients who required reintubation. Following
      use of the extubation checklist, documentation of patient readiness for
      extubation increased from 54% to 92.5%, and extubation failures decreased from
      2.5 per month to 7.2 per month. This study confirmed that extubation failure
      occurred less frequently when the extubation checklist was used (P = .001, Fisher
      exact test). Study results indicate that an extubation checklist may positively
      influence provider documentation of evidence-based criteria for extubation and
      can reduce the occurrence of preventable extubation failures.

PMID- 22848979
TI  - Skin electrical resistance does not change following infraclavicular block.
AB  - Peripheral nerve blocks are common and effective means for anesthesia for limb
      surgery. The evaluation of the success of a peripheral blockade is based on the
      loss of sensation, with no objective means of detecting a successful block. The
      autonomic innervation to the upper extremity, which controls both the vascular
      tone and the activity of sweat glands, is supplied by nerve fibers accompanying
      the somatic nerve fibers. Previous studies have shown changes in both skin
      temperature and electrical resistance of the skin following brachial plexus
      block. We studied 20 patients undergoing hand surgery under infraclavicular
      brachial plexus block. The electrical resistance of the skin on the palmar aspect
      of the forearm was continuously recorded on the block arm and on the
      contralateral arm using a commercial skin resistance monitor. No statistically
      significant change in the electrical resistance of the skin was observed during
      20 minutes after placement of the block. These results strongly suggest that the
      electrical resistance of the skin cannot be used to predict a successful
      infraclavicular block.

PMID- 22848980
TI  - High-fidelity simulation for continuing education in nurse anesthesia.
AB  - Simulation represents a true paradigm shift in teaching and learning that has
      revolutionized healthcare education. However, few continuing education
      opportunities for anesthesia providers exist using simulation of any type. This
      article explores the usefulness of high-fidelity simulation (HFS) as a valuable
      tool for continuing education and reports the results of a needs assessment
      conducted among 22 practicing nurse anesthetists. The questions related to their
      exposure to HFS and asked them to rank their experience with 11 anesthesia
      events. Next, respondents were asked to rank a similar list of anesthesia events
      that would be useful for continuing education using simulation. Of participants,
      71% ranked advanced cardiac life support scenarios, anesthesia machine mishaps,
      and malignant hyperthermia as highly effective choices for using HFS. Eighty-one
      percent of participants identified that they envision simulation as a valuable
      tool to assess competency, but respondents had mixed written responses when asked
      if simulation should be used for recertification. This needs assessment
      represents a beginning, grassroots attempt to establish nurse anesthetists'
      perceptions related to using HFS as a tool for continuing education.

PMID- 22848981
TI  - Anesthesia for the adult patient with an unrepaired congenital cyanotic heart
      defect: a case report.
AB  - Adult congenital heart disease, previously considered a rare comorbidity, is
      increasingly becoming a reality for today's anesthesia providers. Improvements in
      prenatal diagnosis, sophisticated surgical techniques and equipment, advances in
      pediatric critical care, enhanced efficacy of cardiovascular pharmacologic
      agents, and an overall increase in postrepair survival rates have resulted in an
      estimated population of approximately 800,000 adults with congenital heart
      disease. Despite successful surgical repair or palliation, these individuals
      present the anesthesia provider with a multitude of challenges. Individualized
      care of these fragile patients should be approached with a keen understanding of
      the patient's underlying cardiac anomaly. This case report chronicles the
      anesthetic care of a 36-year-old woman presenting for left-sided ureteroscopy
      with laser lithotripsy and stent placement. Her medical history was remarkable
      for the presence of complex congenital heart disease consisting of multiple
      anomalies: a double-outlet right ventricle, transposition of the great arteries,
      pulmonary stenosis, atrial septal defect, and a hypoplastic left ventricle with
      concomitant mitral valve atresia. General anesthesia was successfully
      administered, with meticulous attention given to maintenance of systemic vascular
      resistance to minimize shunting, oxygenation, administration of preprocedure
      antibiotics, and judicious replacement of intravenous fluids via air-filtered
      tubing.

PMID- 22848982
TI  - Shared experiences of CRNAs who were on duty in New Orleans during Hurricane
      Katrina.
AB  - The purpose of this focused ethnography was to describe the shared experiences of
      certified registered nurse anesthetists (CRNAs) who were on duty in New Orleans,
      Louisiana, during Hurricane Katrina as well as to elucidate the psychosocial
      impact the storm had on them. Ten CRNAs participated in 1 of 3 focus groups that
      were audio recorded. The audio recordings were transcribed and analyzed using
      qualitative data analysis computer software (NVivo 8, QSR International,
      Melbourne, Australia). Six major themes emerged from the study: caught off guard;
      sense of duty; uncertainty/powerlessness/frustration; group identity and
      cohesiveness; anger; and life-changing event. The themes represented how the
      CRNAs appraised and coped with the stressful events surrounding Hurricane
      Katrina. The psychosocial impact of Hurricane Katrina on the CRNAs resulted
      mainly in short-term sleep disturbances and increased drinking. Only 2 CRNAs
      expressed long-term psychosocial effects from the storm. The results of this
      study should be used to guide policies regarding disaster activation of CRNAs, to
      educate CRNAs on preparing for disaster duty, and to provide a framework for
      future disaster studies regarding CRNAs.

PMID- 22848983
TI  - A Preventive intervention for rising intraocular pressure: development of the
      Molloy/Bridgeport anesthesia associates observation scale.
AB  - There is increasing interest in monitoring intraocular pressure (IOP) during
      surgery in steep Trendelenburg position because of reported incidents of
      postoperative visual loss (POVL). A review of 17 patients with POVLs showed
      findings of eyelid edema, chemosis, and ecchymosis. The aim of this study was to
      link IOP tonometry measurement to an observation scale enabling caregivers to
      determine when to institute preventive measures to optimize ocular perfusion. The
      study design was a prospective repeated-measures correlation regression model.
      Visual assessment of presence of eyelid edema or chemosis and baseline IOP values
      determined the probability of when an IOP greater than 40 mm Hg (critical
      threshold) was reached. Both IOP and Molloy/Bridgeport Anesthesia Associates
      Observation Scale measures were recorded at start of surgery, 30-minute
      intervals, and end of surgery. Associations between IOP and facial observations
      were analyzed via multiple logistic regression. Significant predictors of IOP
      greater than 40 mm Hg were determined to be presence of chemosis and baseline IOP
      and significantly correlated to increasing IOP. The receiver operating
      characteristic curve-area under the curve score was 0.86 (standard error +/-
      0.03). Caregivers can use this observation scale to assess the need and timing
      for IOP-normalizing interventions and possibly to prevent POVL.

PMID- 22848984
TI  - Update for nurse anesthetists evidence-based anesthesia: The use of preprocedural
      ultrasonography during labor to facilitate placement of an epidural catheter.
AB  - Placement of an epidural catheter in parturients can be challenging because the
      anatomic changes of pregnancy may make it difficult to palpate an ideal insertion
      point or detect loss of resistance. Preprocedural ultrasonography (U/S-P) is
      reported to facilitate placement of epidural catheters in parturients. U/S-P
      provides information on the ideal insertion point, angle of needle insertion, and
      estimated depth to the epidural space. The purposes of this course are to
      describe the technique, systematically review the literature, and discuss
      techniques for integrating U/S-P into practice. It provides evidence
      demonstrating that U/S-P is a useful adjunct for placement of epidural catheters
      in obstetrical patients, especially patients with presumed "difficult backs" or
      obesity.

PMID- 22848985
TI  - Challenging times call for creative measures.

PMID- 22848986
TI  - MGMA encourages HHS to revise the proposed health plan identifier introduced to
      ease administrative burdens.

PMID- 22848987
TI  - CMS introduces enhancements to PECOS and Medicare enrollment policy changes.

PMID- 22848988
TI  - Using automated intelligence to increase reimbursement rates. A discussion with
      Mary Lois Moss, practice manager, Regional Hematology and Oncology, P.A.

PMID- 22848989
TI  - Unintended consequences:. a Goldilocks story.

PMID- 22848990
TI  - Physician-led quality program yields lifesaving results.

PMID- 22848991
TI  - In a twitter about social media? Patients assume you're already online.
      Association members share learnings from web efforts.

PMID- 22848992
TI  - Preventive medicine pays: new coverage rules for wellness counseling.

PMID- 22848993
TI  - Transforming into a patient-centered medical home: a case study.

PMID- 22848994
TI  - MGMA-ACMPE award winners say the honor has a lifelong impact.
AB  - Past MGMA-ACMPE award recipients describe receiving these industry awards as
      inspirational Wha and an honor--and say the experience prompts expceen them to
      continually reach for excellence.

PMID- 22848995
TI  - Finances top challenge charts for association members. Exclusive findings from
      annual Medical Practice Today: what members have to say research.
AB  - Learn which issues--out of a list of 52--are most applicable and intense foryou
      and your colleagues in this year's "Medical Practice Today: What members have to
      say" research. To help you find solutions for those issues, we have paired the
      top 10 challenges (identified by our applicability-weighted index) with MGMA
      ACMPE resources on pages 52 and 53.

PMID- 22848996
TI  - Reading between the lines: how applicable and intense are industry challenges?
      MGMA-ACMPE analyzes member data.

PMID- 22848997
TI  - The sciences of subjectivity.
AB  - In historical and ethnographic studies of the making of scientific knowledge,
      there has been a long-standing fascination with deflating certain stories about
      objectivity. Among the resources used to achieve that deflation have been the
      notions of subjectivity, which has been treated more as a trouble for objectivity
      than as a knowledge-making mode open to systematic study. I describe notions of
      subjectivity implicated in that inattention; I trace potentially constructive
      links between contemporary science studies and resources in 18th-century
      philosophical aesthetics; I draw notice to available engagements with the mode of
      subjectivity known as taste, and, especially, gustation and olfaction; and I
      suggest ways in which we might study the achievement of intersubjectivity in
      these domains.

PMID- 22848998
TI  - When humans are the exception: cross-species databases at the interface of
      biological and clinical research.
AB  - Cross-species comparison has long been regarded as a stepping-stone for medical
      research, enabling the discovery and testing of prospective treatments before
      they undergo clinical trial on humans. Post-genomic medicine has made cross
      species comparison crucial in another respect: the 'community databases'
      developed to collect and disseminate data on model organisms are now often used
      as a template for the dissemination of data on humans and as a tool for comparing
      results of medical significance across the human-animal boundary. This paper
      identifies and discusses four key problems encountered by database curators when
      integrating human and non-human data within the same database: (1) picking
      criteria for what counts as reliable evidence, (2) selecting metadata, (3)
      standardising and describing research materials and (4) choosing nomenclature to
      classify data. An analysis of these hurdles reveals epistemic disagreement and
      controversies underlying cross-species comparisons, which in turn highlight
      important differences in the experimental cultures of biologists and clinicians
      trying to make sense of these data. By considering database development through
      the eyes of curators, this study casts new light on the complex conjunctions of
      biological and clinical practice, model organisms and human subjects, and
      material and virtual sources of evidence--thus emphasizing the fragmented,
      localized and inherently translational nature of biomedicine.

PMID- 22848999
TI  - Credibility battles in the autism litigation.
AB  - That vaccines do not cause autism is now a widely accepted proposition, though a
      few dissenters remain. An 8-year court process in the US federal vaccine injury
      compensation court ended in 2010 with rulings that autism was not an adverse
      reaction to vaccination. There were two sets of trials: one against the measles
      mumps-rubella (MMR) vaccine and one against the mercury-based preservative
      thimerosal. The MMR story is more widely known because of publicity surrounding
      the main proponent of an MMR-autism link, British doctor Andrew Wakefield, but
      the story of thimerosal in court is largely untold. This study examines the
      credibility battles and boundary work in the two cases, illuminating the
      sustaining world of alternative science that supported the parents, lawyers,
      researchers, and expert witnesses against vaccines. After the loss in court, the
      families and their advocates transformed their scientific arguments into an
      indictment of procedural injustice in the vaccine court. I argue that the very
      efforts designed to produce legitimacy in this type of lopsided dispute will be
      counter-mobilized as evidence of injustice, helping us understand why settling a
      scientific controversy in court does not necessarily mean changing anyone's mind.

PMID- 22849000
TI  - Pharmaceutical prospects: biopharming and the geography of technological
      expectations.
AB  - The paper explores the role of imagined geographies in the shaping of new
      technologies. I argue that the role of place in future-oriented visions of
      technoscience is a neglected topic in studies of the social shaping of
      technology. The paper proposes an approach that combines the sociology of
      expectations with the geography of science. It focuses on the interplay between
      envisaged and current geographies to highlight the recursive dynamics of place
      and imagination. To illustrate this approach, the paper discusses the example of
      biopharming, the production of biopharmaceuticals using genetically modified
      crops. I argue that expectations for biopharming bear the imprint of place, or
      rather of the places in which they are imagined, as well as those they imagine,
      and ultimately those they produce. I use this example to suggest how social
      studies of science and technology can usefully investigate the spaces, places and
      scales of technological development.

PMID- 22849001
TI  - The matilda effect in science: awards and prizes in the US, 1990s and 2000s.
AB  - Science is stratified, with an unequal distribution of research facilities and
      rewards among scientists. Awards and prizes, which are critical for shaping
      scientific career trajectories, play a role in this stratification when they
      differentially enhance the status of scientists who already have large
      reputations: the 'Matthew Effect'. Contrary to the Mertonian norm of universalism
      -the expectation that the personal attributes of scientists do not affect
      evaluations of their scientific claims and contributions--in practice, a great
      deal of evidence suggests that the scientific efforts and achievements of women
      do not receive the same recognition as do those of men: the 'Matilda Effect'.
      Awards in science, technology, engineering and medical (STEM) fields are not
      immune to these biases. We outline the research on gender bias in evaluations of
      research and analyze data from 13 STEM disciplinary societies. While women's
      receipt of professional awards and prizes has increased in the past two decades,
      men continue to win a higher proportion of awards for scholarly research than
      expected based on their representation in the nomination pool. The results
      support the powerful twin influences of implicit bias and committee chairs as
      contributing factors. The analysis sheds light on the relationship of external
      social factors to women's science careers and helps to explain why women are
      severely underrepresented as winners of science awards. The ghettoization of
      women's accomplishments into a category of 'women-only' awards also is discussed.

PMID- 22849002
TI  - Can't a mother sing the blues? Postpartum depression and the construction of
      motherhood in late 20th-century America.
AB  - Popular depictions of 20th-century American motherhood have typically emphasized
      the joy and fulfillment that a new mother can expect to experience on her child's
      arrival. But starting in the 1950s, discussions of the "baby blues" began to
      appear in the popular press. How did articles about the baby blues, and then
      postpartum depression, challenge these rosy depictions? In this article, we
      examine portrayals of postpartum distress in popular magazines and advice books
      during the second half of the 20th century to examine how the unsettling pairing
      of distress and motherhood was culturally negotiated in these decades. We show
      that these portrayals revealed a persistent reluctance to situate motherhood
      itself as the cause of serious emotional distress and a consistent focus on
      changing mothers to adapt to their role rather than changing the parameters of
      the role itself. Regardless of whether these messages actually helped or hindered
      new mothers themselves, we suggest that they reflected the rarely challenged
      assumption that motherhood and distress should not mix.

PMID- 22849003
TI  - Delsartean hypnosis for girls' bodies and minds: Annie Payson Call and the Lasell
      Seminary nerve training controversy.
AB  - In the summer of 1890, news that two students at Lasell Seminary for Young Women
      in Auburndale, MA had suffered a complete nervous collapse as a result of being
      hypnotized by an instructor in a nerve training class caused a brief but sharp
      national sensation regarding hypnotism and nerve training in girls' education.
      The instructor, Annie Payson Call, denied practicing hypnotism, and the
      seminary's principal defended both Call and the "mind concentration" course she
      taught at Lasell. Call's approach to nerve training blended Delsartean relaxation
      exercises, New Thought psychology, and self-hypnotic techniques into a
      therapeutic regimen which can be termed "Delsartean hypnosis." Developed further
      in her 1891 popular self-help handbook, Power Through Repose, Call's variety of
      Delsartean hypnosis was incorporated into the procedures of proponents of
      suggestive therapeutics, and it served as a model for subsequent relaxation
      training programs in the early- and mid-20th century.

PMID- 22849004
TI  - "Be the love of god rather than talk about it": ministers study psychology.
AB  - After World War II, American ministers successfully drew on training in
      psychology to nurture their spiritual and vocational development. Contrary to
      what critics of a therapeutic ethos in American culture have asserted, this
      social history of ministers shows that their adoption of psychological modes of
      thinking was neither atomizing nor secularizing. Rather, it helped them become
      better people and better ministers. It nurtured their faith as well as their
      social connections. Thus, I argue against critics who have feared the civically
      enervating effects of psychological outlooks in American society.

PMID- 22849005
TI  - Philip G. Zimbardo on his career and the Stanford Prison Experiment's 40th
      anniversary. Interview by Scott Drury, Scott A. Hutchens, Duane E. Shuttlesworth,
      and Carole L. White.
AB  - We interviewed Philip G. Zimbardo on April 19, 2011, in anticipation of the 40th
      anniversary of the Stanford Prison Experiment in August 2011. While Zimbardo's
      name is mentioned often in tandem with the experiment, he has distinguished
      himself in many other areas within psychology before and after the experiment,
      beginning with an accomplished early career at New York University in which he
      took interest in social psychology research on deindividuation. We discussed the
      Stanford Prison Experiment in the greater context of his varied and illustrious
      career, including recent pioneering work on heroism, the establishment of The
      Shyness Clinic at Stanford University, and the iconic Discovering Psychology
      series. We also addressed his adroit and candid approach to the experiment itself
      over the years.

PMID- 22849006
TI  - Visual illusions and ethnocentrism: exemplars for teaching cross-cultural
      concepts.
AB  - This article discusses the origins of cross-cultural interest in two concepts
      fundamental to psychology students' views of the world: simple visual illusions
      and ethnocentrism. Although students encounter these ideas in introductory
      psychology, textbooks rarely describe the nature or origin of cross-cultural
      knowledge about them. The article presents a brief account of the history of
      these concepts and relates them to contemporary notions of psychology and
      culture. Using visual perception and ethnocentrism as examples, the article
      suggests the importance of teaching that different people see the world in
      different ways and the role of that lesson in a future demanding increased cross
      cultural understanding.

PMID- 22849007
TI  - The wonder of their voices: The 1946 Holocaust interviews of David Boder (New
      York: Oxford, 2010).
AB  - Writing a study of psychologist David Boder's 1946 displaced persons (DP)
      interview project gave me a chance to further document the substantial early
      response to the Holocaust. This was clearly one important piece of my study, and
      one that was eminently straightforward. Yet much of the research on Boder's
      project at the point in time that I carried it out was elliptical, partly because
      the primary interview materials were coming to light at an astonishing pace,
      partly because the archive collections were virtually untapped, and partly
      because of the misconception of Boder and his interview project itself.

PMID- 22849008
TI  - Gender, ethnicity, and career trajectories: a comment on Woodward (2010).
AB  - Woodward (2010) argued that Maria Rickers-Ovsiankina, Eugenia Hanfmann, and
      Tamara Dembo constituted a group of Jewish emigre psychologists who received
      substantial help in America from a "Jewish network" of patronage. This comment
      focuses on the historiographic problems and pitfalls of essentialized ethnic
      identification. There was no evidence that Maria Rickers-Ovsiankina was a Jew or
      that Eugenia Hanffman, raised Russian Orthodox, identified herself as a Jew, in
      contrast to Tamara Dembo, who did so. We argue that these women were part of an
      active network of Gestaltists, topologists, and Society for the Psychological
      Study of Social Issues leaders, and that any help that they received may be
      explained by the shared theoretical and disciplinary outlook of these groups as
      opposed to a "Jewish network."

PMID- 22849009
TI  - Introduction: how can we afford to die?

PMID- 22849010
TI  - End-of-life care in United States: current reality and future promise--a policy
      review.
AB  - Data collection and analysis of that data are vital to developing effective
      outcome measures when it comes to improvements in the cost and quality of
      delivered health care. The present state of end-of-life care in the United States
      is evaluated, focusing on statistics of disparities in access to and type of care
      provided across the country. Although only a few portions of the Patient
      Protection and Affordable Care Act deal with end-of-life care reform, the
      multiple innovative efforts occurring at state and local levels are proving very
      effective in improving end-of-life care. Possible improvements and obstacles to
      those improvements, and the involvement of the profession of nursing are
      highlighted. The focus of this investigation is to determine if the evidence
      supports the following imperative: that the money spent for end-of-life care be
      spent in a manner that benefits the patient and complements his or her wishes.

PMID- 22849011
TI  - Economic and legal issues in end-of-life care: An Interview with Michael Ash and
      Stephen Arons. Interview by Joanne Spetz.

PMID- 22849012
TI  - Nurses leading the response to the crisis of palliative care for vulnerable
      populations.
AB  - All nurses are prepared to be generalists in palliative care. Within the
      discipline there are nurses who seek advanced educational preparation and develop
      clinical expertise in palliative care nursing. These are our leaders in
      palliative care nursing who can exert influence in all health care settings to
      support nurses providing palliative care. It is nurses and advanced practice
      nurses in partnership who are capable of developing and advocating for palliative
      care across settings. The focus of care is the person, not the diagnosis or the
      setting. The viewpoint that "all nursing care is palliative care" can transform
      health care with nurses taking the lead.

PMID- 22849013
TI  - Death is not an option, how you die is--reflections from a career in oncology
      nursing.
AB  - With a combined career of over 60 years in oncology nursing, the authors reflect
      on the critical elements in the question, "How can we afford to die?" Three high
      profile patient scenarios in three different decades promised to improve use of
      advance directives but did not. Recent societal events, including the debates
      about health care reform, have brought attention again to end-of-life issues and
      care. Quickly approaching a "perfect storm" of an aging population, an
      inefficient and costly illness-oriented health care system, and health care
      profession shortages, the United States will not be able to afford delivering
      futile interventions. Nurses, who are consistently seen as the most trusted
      professionals, must take action in strategies the authors present.

PMID- 22849014
TI  - Palliative care: a paradigm of care responsive to the demands for health care
      reform in America.
AB  - Palliative care is poised to become a universally available approach to health
      care which addresses both the needs of patients and families experiencing
      serious, progressive, and life-threatening illness, and also the costs of
      delivering such needed services. Palliative care and hospice are part of a
      continuum of care with palliative care provided at any time during the illness
      trajectory, while hospice care is offered at the end of life. Within the context
      of health care reform, we believe palliative care addresses critical economic
      imperatives while enhancing quality of life even as death approaches. As leaders
      in health care, advance practice nurses, specifically, and the nursing community
      in general are best positioned with the knowledge, expertise, and commitment to
      advance the specialty of palliative care and lead the way in the reform of
      America's health care system.

PMID- 22849015
TI  - End-of-life care in nursing homes: the high cost of staff turnover.
AB  - Nursing home staff turnover results in high cost--both economic and personal--and
      has a negative impact on the quality of care provided to residents at the end of
      life. Reducing staff turnover in nursing homes would benefit both the cost to the
      U.S. health care system, and, most importantly, the care residents receive in the
      vulnerable period leading to death. There is rising pressure on nursing homes to
      improve their palliative and end-of-life care practices and reduce transfers to
      hospital for situations and conditions that can be safely managed on site.
      Nursing care staff deserve an investment in the specific training necessary for
      them to give the highest quality care to dying residents. This training should be
      multifaceted and include the physiological, psychological, spiritual,
      interpersonal, and cultural (including ethnic) aspects of dying. Empowerment with
      these necessary knowledge, skills, and attitudes will not only result in better
      care for residents but likely also will reduce the burnout and frustration staff
      experience in caring for residents near death.

PMID- 22849016
TI  - Staffing for end of life: challenges and opportunities.
AB  - What would staffing look like if we committed to end-of-life experiences that
      were designed to honor the needs of the person dying, their loved ones, and the
      needs of the nurses and care team involved in the dying experience? When we think
      about the experience of death in a health care setting, it is essential we look
      at the needs of both patients and caregivers. Attending to the needs of patients
      and their families facing death, even if well defined, can be difficult to design
      into staffing plans and budgets in a way that would not put an organization at
      further financial risk. If we are going to commit to staffing practices that
      honor dying, in all it's dimensions and for all who are potentially impacted, we
      will most likely have to step outside traditional thinking to find answers.

PMID- 22849017
TI  - Community discussions: a vision for cutting the costs of end-of-life care.
AB  - Palliative care involvement with patients with advanced disease has demonstrated
      significant cost savings at end of life (EOL). These financial benefits are
      largely due to improved EOL decision making. Assisting patients and families to
      examine their values and determine their preferences makes it possible to match
      patient goals with appropriate care. Often, comfort-oriented care is favored,
      avoiding the costs of medically aggressive, often futile, technology-driven
      interventions. Community-based EOL care discussions would demonstrate increased
      cost reductions while facilitating significant patient and family satisfaction
      with care.

PMID- 22849018
TI  - Courage, leadership, and end-of-life care: when courage counts.
AB  - As leaders, we must feel a sense of moral obligation to implement evidence about
      end-of-life care in our practice setting. Nurse leaders can help patients and
      families orchestrate a beautiful experience that is an alternative to futile,
      expensive end-of-life care. Preparation is key in helping staff provide the best
      level of care. A plan built around the best care for patients can integrate with
      many diverse positions and people. Courageous nurse leaders are well adapted to
      maneuvering through political traps and advocating for patients and their
      families. Everyone benefits personally and financially, including our communities
      and nation, when courageous leaders advocate successfully for effective end-of
      life care.

PMID- 22849019
TI  - 'Affordable' death in the United States: an action plan based on lessons learned
      from the Nursing Economic$ special issue.
AB  - An eight-point action plan is proposed for lowering costs associated with end-of
      life health care in the United States, as well as improving the quality of life
      experienced by patients and their families. This action plan was derived from an
      analysis of the six articles presented in this special issue of Nursing
      Economic$. The two major features of this action plan are: (a) expansion of
      hospice and palliative care, as well as (b) increased use of advance directives.
      Additionally, as pre-conditions for the effective operation of this action plan,
      the political, cultural, and legislative contexts that merit attention are
      discussed. Finally, arguments as to the desirability, feasibility, and
      sustainability of this action plan are offered.

PMID- 22849021
TI  - 'Intelligent or' taps technology for patient and material logistics.

PMID- 22849020
TI  - The Final frontier.

PMID- 22849022
TI  - Time busters: a lean team tackles OR turnover.

PMID- 22849023
TI  - Restructuring circulator nurse role aids turnover.

PMID- 22849024
TI  - Visual cues help to improve the turnover process.

PMID- 22849025
TI  - RTLS yields new data for managing patient logistics.

PMID- 22849026
TI  - Thinking about wireless systems? Consider these tips from an expert.

PMID- 22849027
TI  - Workflow support in new Johns Hopkins ORs.

PMID- 22849028
TI  - Tackling perioperative supply chain as a system.

PMID- 22849029
TI  - Medicare rules allow broader use of nonphysicians.

PMID- 22849030
TI  - CMS expert offers advice on ASC quality reporting.

PMID- 22849031
TI  - Aristotle's biological works as scientific literature.
AB  - This contribution deals with the question of where and why in his biological
      writings Aristotle uses dialogical elements, examining which dialogical
      structures can be found and what the meaning of the dialogical structures is in
      respect of the argumentative strategies used in literature. This discursive style
      has to be seen in relation to the importance of the dialectical method which was
      practiced in the Platonic Academy and on which Aristotle reflected in his Topics.
      For Aristotle the dialectical method also becomes the method of the investigator
      researching for himself. But more than that one can see the reason for the
      dialogical structures in Aristotle's writings in his attempt to combine the way
      of acquiring knowledge with the way of presenting knowledge. It can thus be said
      that at the moment in which the dialectical procedure is translated into the
      medium of writing, a fact-oriented presentation is also an addressee-oriented
      representation. Nowadays we are more accustomed to a technical literature which,
      after completing the first step of the deduction of knowledge, presents the
      results in a systematic and hierarchical way in its literary representation; in
      such technical literature, normally an individual's thought process is not set
      out in writing. Admittedly, with the application of the dialectical method and
      with the attempt to set down one's own thought process in the medium of writing,
      other elements also come in.

PMID- 22849032
TI  - And to end on a poetic note: Galen's authorial strategies in the pharmacological
      books.
AB  - This paper examines the authorial strategies deployed by Galen in his two main
      pharmacological treatises devoted to compound remedies: Composition of Medicines
      according to Types and Composition of Medicines according to Places. Some of
      Galen's methods of self assertion (use of the first person; writing of prefaces)
      are conventional. Others have not received much attention from scholars. Thus,
      here, I examine Galen's borrowing of his sources' 'I'; his use of the phrase 'in
      these words'; and his recourse to Damocrates' verse to conclude pharmacological
      books. I argue that Galen's authorial persona is very different from that of the
      modern author as defined by Roland Barthes. Galen imitates and impersonates his
      pharmacological sources. This re-enactment becomes a way to gain experience
      (peira) of remedies and guarantees their efficacy.

PMID- 22849033
TI  - Gender and philosophy of science: The case of Mary Hesse.
AB  - This article is composed of two intertwining narratives. The first is a
      discussion of the concept of gender in relation to philosopher of science Mary
      Hesse's theoretical contributions and academic experiences. The second narrative
      takes issue with the gender concept at a more general level and particularly to
      discuss its strengths and limits. The article alternates between a discussion of
      different claims from gender theorists and a presentation of Mary Hesse's
      academic experiences. I conclude that although the gender concept has, until now,
      only been used in an asymmetrical sense, i.e., negatively linked to women's
      careers and positively to men's, it will not necessarily be identically used in
      the future. Both empirical findings and conceptual changes may make room for a
      more differentiated understanding of gender.

PMID- 22849035
TI  - A mindfulness course decreases burnout and improves well-being among healthcare
      providers.
AB  - OBJECTIVE: Healthcare providers are under increasing stress and work-related
      burnout has become common. Mindfulness-based interventions have a potential role
      in decreasing stress and burnout. The purpose of this study was to determine if a
      continuing education course based on mindfulness-based stress reduction could
      decrease burnout and improve mental well-being among healthcare providers, from
      different professions. DESIGN: This was a pre-post observational study conducted
      in a university medical center. A total of 93 healthcare providers, including
      physicians from multiple specialties, nurses, psychologists, and social workers
      who practiced in both university and community settings, participated. The
      intervention was a continuing education course based on mindfulness-based stress
      reduction that met 2.5 hours a week for 8 weeks plus a 7-hour retreat. The
      classes included training in four types of formal mindfulness practices,
      including the body scan, mindful movement, walking meditation and sitting
      meditation, as well as discussion focusing on the application of mindfulness at
      work. The course was offered 11 times over 6 years. The main outcome measures
      were work-related burnout as measured by the Maslach Burnout Inventory and self
      perceived mental and physical well-being as measured by the SF-12v2. RESULTS:
      Maslach Burnout Inventory scores improved significantly from before to after the
      course for both physicians and other healthcare providers for the Emotional
      Exhaustion (p < 0.03), Depersonalization (p < 0.04), and Personal Accomplishment
      (p < 0.001) scales. Mental well-being measured by the SF12v2 also improved
      significantly (p < 0.001). There were no significant changes in the SF12v2
      physical health scores. CONCLUSION: A continuing education course based on
      mindfulness-based stress reduction was associated with significant improvements
      in burnout scores and mental well-being for a broad range of healthcare
      providers.

PMID- 22849034
TI  - Feasibility of nurse-led antidepressant medication management of depression in an
      HIV clinic in Tanzania.
AB  - OBJECTIVE: Sub-Saharan Africa has the highest HIV prevalence worldwide and
      depression is highly prevalent among those infected. The negative impact of
      depression on HIV outcomes highlights the need to identify and treat it in this
      population. A model for doing this in lower-resourced settings involves task
      shifting depression treatment to primary care; however, HIV-infected individuals
      are often treated in a parallel HIV specialty setting. We adapted a model of task
      shifting, measurement-based care (MBC), for an HIV clinic setting and tested its
      feasibility in Tanzania. MBC involves measuring depressive symptoms at meaningful
      intervals and adjusting antidepressant medication treatment based on the measure
      of illness. METHOD: Twenty adults presenting for care at an outpatient HIV clinic
      in Tanzania were enrolled and followed by a nurse care manager who measured
      depressive symptoms at baseline and every 4 weeks for 12 weeks. An algorithm
      based decision-support tool was utilized by the care manager to recommend
      individualized antidepressant medication doses to participants' HIV providers at
      each visit. RESULTS: Retention was high and fidelity of the care manager to the
      MBC protocol was exceptional. Follow through of antidepressant prescription
      dosing recommendations by the prescriber was low. Limited availability of
      antidepressants was also noted. Despite challenges, baseline depression scores
      decreased over the 12-week period. CONCLUSIONS: Overall, the model of algorithm
      based nursing support of prescription decisions was feasible. Future studies
      should address implementation issues of medication supply and dosing. Further
      task-shifting to relatively more abundant and lower-skilled health workers, such
      as nurses' aides, warrants examination.

PMID- 22849036
TI  - Brief psychotherapy for depression: a systematic review and meta-analysis.
AB  - OBJECTIVE: Because evidence-based psychotherapies of 12 to 20 sessions can be
      perceived as too lengthy and time intensive for the treatment of depression in
      primary care, a number of studies have examined abbreviated psychotherapy
      protocols. The purpose of this study was to conduct a systematic review and meta
      analysis to determine the efficacy of brief psychotherapy (i.e., < or =8
      sessions) for depression. METHODS: We used combined literature searches in
      PubMed, EMBASE, PsycINFO, and an Internet-accessible database of clinical trials
      of psychotherapy to conduct two systematic searches: one for existing systematic
      reviews and another for randomized controlled trials (RCTs). Included studies
      examined evidence-based psychotherapy(s) of eight or fewer sessions, focused on
      adults with depression, contained an acceptable control condition, were published
      in English, and used validated measures of depressive symptoms. RESULTS: We
      retained 2 systematic reviews and 15 RCTs evaluating cognitive behavioral
      therapy, problem-solving therapy, and mindfulness-based cognitive therapy. The
      systematic reviews found brief psychotherapies to be more efficacious than
      control, with effect sizes ranging from -0.33 to -0.25. Our meta-analysis found
      six to eight sessions of cognitive behavioral therapy to be more efficacious than
      control (ES -0.42, 95% CI -0.74 to -0.10, 12 = 56%). A sensitivity analysis
      controlled for statistical heterogeneity but showed smaller treatment effects (ES
      -0.24, 95% CI -0.42 to -0.06, 12 = 0%). CONCLUSIONS: Depression can be
      efficaciously treated with six to eight sessions of psychotherapy, particularly
      cognitive behavioral therapy and problem-solving therapy. Access to non
      pharmacologic treatments for depression could be improved by training healthcare
      providers to deliver brief psychotherapies.

PMID- 22849037
TI  - Reliability of self-reported tobacco use in bipolar disorder: an exploratory
      study of euthymic patients visiting a tertiary care hospital in India.
AB  - BACKGROUND: Unlike schizophrenia, only a little attention has been paid to
      tobacco dependence in patients with bipolar disorder despite a similarly high
      prevalence and predisposition to health risks. The euthymic phase is especially
      suitable for tobacco screening by the treating psychiatrist. However, the
      validity of self-report for tobacco use in this patient population remains
      undetermined. AIM: The current study aims to assess the validity of self-reported
      tobacco use in euthymic bipolar disorder. METHOD: The psychiatric out-patients
      with DSM-IV TR diagnosis of bipolar type-I in remission who were males, > or =18
      years, and euthymic as established by current scores of <7 on HAM-D and <4 on
      YMRS. Patients were specifically asked for the recent use of tobacco in any form.
      Ten ml urine sample was obtained after informed consent and subjected to a
      quantitative cotinine estimation by direct enzyme-linked immunosorbent assay.
      RESULTS: A total of 100 patients were screened, of which 79 were finally
      included. The self-report for recent tobacco use showed only a moderate
      concordance with urinary cotinine (k = 0.518) and cotinine-creatinine ratio (k =
      0.492). Over 15% patients had denied the use of tobacco, but tested positive on
      urinary cotinine assessment. The sensitivity of self-report was 73.3% compared to
      urinary cotinine. The denial among users was 26.7% and denial among those with
      negative self-report was 30.8%. CONCLUSION: Mental health professionals should be
      vigilant for detection of tobacco dependence among remitted bipolar patients, who
      may not be so forthcoming about their tobacco use.

PMID- 22849039
TI  - The prevalence of 22 self-harm behaviors in a consecutive sample of
      obstetrics/gynecology outpatients.
AB  - BACKGROUND: While a number of previous studies have examined limited forms of
      self-harm behavior, such as suicidal ideation/attempts/completions, or one
      specific behavior such as cutting or burning oneself(most frequently in
      psychiatric populations), few studies have examined the lifetime prevalence of
      multiple self-harm behaviors in a single non-psychiatric population and no study
      has done so among obstetrics/gynecology outpatients. METHOD: Using a cross
      sectional consecutive sample of 370 women presenting to an obstetrics/gynecology
      outpatient clinic and a self-report survey methodology, we examined the lifetime
      prevalence of 22 self-harm behaviors. RESULTS: In this sample, the most
      frequently self-reported self-harm behaviors were: engaged in emotionally abusive
      relationships (24.7%), abused alcohol (22.0%), been promiscuous (21.0%),
      attempted suicide (18.3%), and tortured self with self-defeating thoughts
      (16.7%). Four of these preceding behaviors were also the most commonly reported 5
      of 22 behaviors in 3 previous studies of self-harm behavior in different clinical
      populations. CONCLUSIONS: It appears that the most frequently reported lifetime
      self-harm behaviors are relatively common across various non-psychiatric clinical
      populations of adults, albeit in different proportions, with some exceptions
      (i.e., suicide attempts in the present sample).

PMID- 22849038
TI  - The association between childhood adversity and components of metabolic syndrome
      in adults with mood disorders: results from the international mood disorders
      collaborative project.
AB  - OBJECTIVE: We sought to determine whether a reported history of childhood
      adversity is associated with components of the National Cholesterol Education
      Program Adult Treatment Panel III (NCEP-ATP-III)-defined metabolic syndrome in
      adults with mood disorders. METHOD: This was a cross-sectional analysis of adult
      outpatients (N = 373; n = 230 female, n = 143 male; mean age [SD] = 42.86
      [14.43]) from the International Mood Disorders Collaborative Project (University
      of Toronto and Cleveland Clinic) with DSM-IV-defined major depressive disorder
      and bipolar I/II disorder. Childhood adversity was measured with the Klein Trauma
      & Abuse-Neglect self-report scale. The groups with and without childhood
      adversity were compared to determine possible differences in the rates of
      metabolic syndrome and its components. Logistic and linear regressions adjusted
      for age, sex, education, employment status, and smoking were used to evaluate the
      association between childhood adversity and components of metabolic syndrome.
      RESULTS: For the full sample, 83 subjects (22.25%) met criteria for metabolic
      syndrome. Individuals reporting a history of any childhood adversity had higher
      systolic and diastolic blood pressure (systolic: p = 0.040; diastolic: p =
      0.038). Among subjects with a history of sexual abuse, a significant proportion
      met criteria for obesity (45.28% vs. 32.88%; p = 0.010); a trend toward
      overweight was found for subjects with a history of physical abuse (76.32% vs.
      63.33%; p = 0.074), although this relationship did not remain significant after
      adjusting for potential confounders. There was no statistically significant
      difference in the overall rate of dyslipidemia and/or metabolic syndrome between
      subjects with and without childhood adversity. CONCLUSION: The results herein
      provide preliminary evidence suggesting that childhood adversity is associated
      with metabolic syndrome components in individuals with mood disorders.

PMID- 22849041
TI  - Clarity at last. Providers welcome justices' long-awaited ACA ruling, will focus
      now on implementing law.

PMID- 22849040
TI  - Brain event-related potentials associated with psychiatric symptoms in
      amphetamine-type stimulant dependent patients.
AB  - OBJECTIVE: To explore the correlation between brain event-related potentials
      (ERPs) and psychiatric symptoms in patients with amphetamine-type stimulants
      (ATS) dependence. METHOD: Using Galileo Sirius 32-channels digital-evoked
      potential system, we measured the auditory P300 ERP in 40 ATS dependence subjects
      and 30 normal controls, respectively. Symptom Checklist 90 (SCL-90) was used to
      rate the psychiatric symptoms in the subjects. RESULTS: In ATS dependence
      subjects, the latency of N2, latency of P3, and inter-peak latency of P2-N2 were
      significantly longer than those in controls, respectively (P < 0.05). The
      amplitude of P300 in ATS dependence subjects was significantly lower than that in
      controls (P < 0.01). Besides, significantly lower amplitude of P3 and longer
      latency of P3 were found in ATS dependence subjects suffering from psychiatric
      symptoms than those without psychotic symptoms (P < 0.05). Furthermore, in ATS
      dependence subjects, the latency of N2 was negatively correlated with the scores
      of anxiety factor (r = -0.366) and paranoid ideation factor of SCL-90; the
      latency of P3 negatively correlated with the scores of psychoticism (r = -0.430)
      and somatization (r = -0.397) factor; also, the amplitude of P3 was negatively
      correlated with the score ofpsychoticism factor (r = -0.486). CONCLUSIONS: These
      findings suggest cognitive dysfunction may be one of results of ATS dependence.

PMID- 22849042
TI  - Market bump. Stocks for hospitals up, some insurers down.

PMID- 22849044
TI  - It's about time. Court's ruling caps a century of reform struggle and policy
      twists.

PMID- 22849043
TI  - Ahead of the game. ACOs already in place gain momentum.

PMID- 22849045
TI  - Here's to better health, security. Entire healthcare community must work together
      to ensure top-quality care.

PMID- 22849046
TI  - Prevention prevails. Widespread routine care will help minimize severity of
      illness costs.

PMID- 22849047
TI  - Meeting the challenges. Ruling means full attention can be turned to building
      exchanges, enrollment.

PMID- 22849048
TI  - Affordability is key. Attention must be paid to law's provisions that threaten to
      increase costs.

PMID- 22849049
TI  - The next set of challenges. Now it's time to move on to issues involving
      efficiency, sustainability.

PMID- 22849050
TI  - Transparent effect. The ACA will now help to offer clarity on pricing and
      payment.

PMID- 22849051
TI  - Hollow magnetic nanoparticles: synthesis and applications in biomedicine.
AB  - Magnetic hollow particles (MHP) are widely used in biomedicine field due to their
      biocompatibility, low-toxicity, low-density and the large fraction void space in
      the MHP, which have been successfully used to encapsulate and control drugs
      release, and magnetic resonance imaging (MRI). This review focuses on all kinds
      of MHP preparation method, compares the advantages and disadvantages in the
      process of synthesis, and introduces especially the special formation mechanisms
      such as the Kirkendall effect and Ostwald ripening. Both the compatible interior
      space and good magnetism of magnetic hollow structures enable them promising and
      unique candidates as biomedicine vehicles. Particularly, the progress of MHP
      widely used in the biomedical engineering applications containing drug delivery
      and magnetic resonance imaging are described. The main problems and the
      directions in the future researches are pointed out.

PMID- 22849052
TI  - Purification and separation of single-walled carbon nanotubes (SWCNTs).
AB  - Purification or separation of single-walled carbon nanotubes (SWCNTs) is one of
      the most fundamental steps before they are used for research and technological
      applications. Based on the difference of their physical and chemical properties,
      separation of carbon nanotubes (CNTs) can be categorized into three groups:
      length separation, metallic and semiconducting tubes separation and chirality
      separation. In this review, we first briefly review the purification of CNTs and
      then focus on the different methods for the separation of CNTs.

PMID- 22849053
TI  - Preparation and biomedical applications of core-shell silica/magnetic
      nanoparticle composites.
AB  - Core-shell structured silica/magnetic nanoparticle composites have recently been
      subjected to extensive research since the shells could offer protection to the
      cores and introduce new properties to the hybrid structures, which endue them
      with great application potentials in various fields. Several approaches have been
      studied for the synthesis of SiO2 coated on magnetic nanoparticles. These
      approaches include Stober process, microemulsion, sodium silicate and
      tetraethoxysilane hydrolysis, aerosol pyrolysis, layer-by-layer strategy, polymer
      templating and sonochemical deposition. This review is focused on describing
      state-of-the-art synthetic routes and methods for the preparation of
      silica/magnetic nanoparticle composites. Furthermore, we also introduce main
      applications of these nanoparticle composites in biomedical scopes and address
      some challenges in the synthesis of high-quality magnetic nanoparticles.

PMID- 22849054
TI  - Nanomagnets La0.8Pb0.2(Fe0.8Co0.2)O3 assembled with a bonded surface graphene
      oxide: sensitive for sensing small gas molecules.
AB  - Nanocrystallites La0.8Pb0.2(Fe0.8Co0.2)O3 (LPFC) when bonded through a surface
      layer (carbon) in small ensembles display surface sensitive magnetism useful for
      biological probes, electrodes, and toxic gas sensors. A simple dispersion and
      hydrolysis of the salts in ethylene glycol (EG) in water is explored to form
      ensembles of the nanocrystallites (NCs) by combustion of a liquid precursor gel
      slowly in microwave at 70-80 dgrees C (apparent) in a closed container in air. In
      a dilute sample, the EG molecules mediate hydrolyzed species to configure in
      small groups in process to form a gel. Proposed models describe how a residual
      carbon bridges a stable bonded layer of a graphene-oxide-like hybrid structure on
      the LPFC-NCs in attenuating the magnetic structure. SEM images, measured from a
      pelletized sample which was used to study the gas sensing features in terms of
      the electrical resistance, describe plate shaped NCs, typically 30-60 nm widths,
      60-180 nm lengths and -50 m2/g surface area (after heating at -750 degrees C).
      These NCs are arranged in ensembles (200-900 nm size). As per the X-ray
      diffraction, the plates (a Pnma orthorhombic structure) bear only small strain 
      0.0023 N/m2 and oxygen vacancies. The phonon and electronic bands from a bonded
      surface layer disappear when it is etched out slowly by heating above 550 degrees
      C in air. The surface layer actively promotes selective H2 gas sensor properties.

PMID- 22849055
TI  - Anchoring gold nanoparticles on graphene nanosheets functionalized with cationic
      polyelectrolyte: a novel catalyst for 4-nitrophenol reduction.
AB  - In this paper, a stable aqueous dispersion of graphene nanosheets (GNs) has been
      prepared by chemical reduction of graphene oxide (GO) with hydrazine hydrate in
      the presence of poly [(2-ethyldimethylammonioethyl methacrylate ethyl sulfate)-co
      (1-vinylpyrrolidone)] (PQ11). Taking advantages of the fact that PQ11 is a
      positively charged polymer exhibiting reducing ability, we further demonstrated
      the subsequent decoration of GN with gold nanoparticals (AuNPs) by in-situ
      chemical reduction of HAuCl4. It was found that such nanocomposites exhibit good
      catalytic activity toward 4-nitrophenol (4-NP) reduction and the GN supports also
      enhance the catalytic activity via a synergistic effect.

PMID- 22849056
TI  - Functionalized gold nanoparticles self-assemblies with efficient nonlinear
      optical properties.
AB  - Satellite-patterns aggregate structures of gold nanoparticles were fabricated by
      the inducing pi-pi stacking interactions. The self-assembly process of satellite
      patterns was tuned by the controlling ligand exchange on the surface of spherical
      gold nanoparticles, which provide a novel concept and an efficient method for
      controlling self-assembly of gold nanoparticles. With increasing the porphyrin
      alkanethiol ratio (r) of gold nanoparticles, the self-assembly induces to form
      the larger satellite-structures. The study indicates that exchange process of
      tetra-n-octylammonium bromide molecules and porphyrin alkanethiol molecules
      results in the formation of satellite-pattern structures with topological
      features. Nonlinear optical properties of porphyrin alkanethiol capped gold
      nanoparticles of toluene solution were measured using the Z-scan technique, and
      its third-order nonlinear optical susceptibility (chi(3)) is calculated as 0.9 x
      10(-13) esu, presented the third-order nonlinear optical properties. The well
      ordered assembly of gold nanoparticles exhibits controlled the third-order
      nonlinear optical properties, which can be enhanced with the increasing of the
      porphyrin alkanethiol ratio in systems.

PMID- 22849057
TI  - The effect of photo-irradiation on the optical properties of thiol-capped CdTe
      quantum dots.
AB  - In this report, the effect of photo-irradiation on the optical properties of
      thioglycolic acid (TGA) capped CdTe QDs was investigated. The photo-irradiation
      led to an increase in the photoluminescence (PL) efficiency of TGA-capped CdTe
      QDs with a low quantum yield under both the open air and nitrogen atmosphere. The
      photo-irradiation caused a blue-shift of PL peak under the open air and almost no
      change of PL peak position under the nitrogen atmosphere. The XPS study revealed
      the oxidation of the unpassivated surface of the Te atoms which mainly
      contributed to the observed optical property changes for CdTe QDs photo
      irradiated under the open air. While for the CdTe QDs photo-irradiated under the
      nitrogen atmosphere, the decomposition of TGA led to the release of sulphur which
      formed a CdS shell on the CdTe core, resulting in an enhanced PL efficiency.

PMID- 22849058
TI  - Sensitive and selective detection of mercury (II) based on the aggregation of
      gold nanoparticles stabilized by riboflavin.
AB  - Gold nanoparticles (AuNPs) can be stabilized by riboflavin against tris buffer
      induced aggregation. However, in the presence of mercury (II) (Hg2+), riboflavin
      can be released from the AuNPs surface and the riboflavin-Hg2+ complex formed,
      leading to the aggregation of AuNPs in tris buffer. The aggregation extent
      depends on the concentration of Hg2+. Based on the aggregation extent, a simple
      and sensitive method of determining Hg2+ is developed. The method enables the
      detection of Hg2+ over the concentration range of 0.02-0.8 microM, with a
      detection limit (3sigma) of 14 nM, and shows excellent selectivity for Hg2+ over
      other metal ions (Cu2+, Co2+, Cd2+, Pb2+, Mg2+, Zn2+, Ag+, Ce3+, Ca2+, Al3+, K+).
      More importantly, the method avoids complicated surface modifications and tedious
      separation processes.

PMID- 22849059
TI  - Facile synthesis and luminescence characteristics of high-quality CdS: Eu/ZnS
      core/shell nanocrystals with biocompatibility.
AB  - In this paper, we report a facile method to synthesize high quality CdS: Eu
      nanocrystals (NCs) and CdS: Eu/ZnS NCs with strong photoluminescence (PL). The
      influence of various experimental variables including the concentration of Eu3+
      ions, the reaction time and the reaction temperature were investigated
      systematically. In addition, the PL properties of CdS: Eu NCs exhibited pH
      sensitive. Under the acid condition, pH value of the CdS: Eu NCs solution played
      an important role in determining PL emission intensity. However, under the
      alkaline condition, the obtained CdS: Eu NCs exhibited a tunable PL emission
      wavelength (from 490 nm to 610 nm) when pH value was adjusted from pH 7 to 10.
      After coating with ZnS shell, the CdS: Eu/ZnS NCs showed enhanced PL intensity
      compare with one of the CdS: Eu NCs. The CdS: Eu NCs and CdS: Eu/ZnS NCs were
      characterized by X-ray diffraction (XRD) and high-resolution transmission
      electron microscopy (HRTEM). In addition, the biocompatibility of these NCs was
      measured by hemolytic test, which indicated that CdS: Eu/ZnS NCs were more
      biocompatible than CdS: Eu NCs at the same conditions. It can be expected that
      CdS: Eu/ZnS NCs are promising biolabeling materials.

PMID- 22849060
TI  - Surface-enhanced Raman scattering on gold nanotrenches and nanoholes.
AB  - Dependent effects on edge-to-edge distance and incidence polarization in surface
      enhanced Raman Scattering (SERS) were studied in detection of 4-mercaptopyridine
      (4-MPy) molecules absorbed on gold nanotrenches and nanoholes. The gold
      nanostructures with controllable size and period were fabricated using electron
      beam lithography. Large SERS enhancement in detection of 4-MPy molecules on both
      nanostructred substrates was observed. The SERS enhancement increased
      exponentially with decrease of edge-to-edge distance for both the nanotrenches
      and nanoholes while keeping the sizes of the nanotrenches and nanoholes
      unchanged. Investigation of polarization dependence showed that the SERS
      enhancement of nanotrenches was much more sensitive to the incidence
      polarizations than that of nanoholes.

PMID- 22849061
TI  - Electrochemical fabrication of titania nanotube arrays with tunning nature of
      dimethyl sulfoxide and its application for hydrogen sensing.
AB  - In the present work, tuning effects of dimethyl sulphoxide (DMSO) on the length,
      wall thickness, dimension and morphology of titania nanotube arrays fabricated by
      anodization was investigated. DMSO presented in both ethylene glycol and glycerol
      electrolytes provided excellent tunability in length, wall thickness and diameter
      of the produced TiO2 nanotube arrays by systematically varying the DMSO
      concentration. At the DMSO concentration of 12 wt% in ethylene glycol, the
      nanotube length could be up to 13.0 microm at 20 V for 8 h anodization. The TiO2
      nanotube arrays produced in DMSO containing ethylene glycol or glycerol
      electrolytes displayed a high sensitivity to hydrogen at room temperature
      compared to the absence of DMSO. The further enhancement of resistance response
      could be achieved by coating a Pt and Pd layer on the surface of TiO2 nanotube
      arrays. The presented work provided a simple way to control formation of TiO2
      nanotube arrays through the tuning effects of DMSO in ethylene glycol or glycerol
      electrolytes.

PMID- 22849062
TI  - Continuous sorting of microparticles using dielectrophoresis.
AB  - Sorting of particles such as cells is a critical process for many biomedical
      applications, and it is challenging to integrate it into an analytical
      microdevice. We report an effective and flexible dielectrophoresis (DEP)-based
      microfluidic device for continuous sorting of multiple particles in a
      microchannel. The particle sorter is composed of two components-a DEP focusing
      unit and a Movable DEP Trap (MDT). The trap is formed by an array of
      microelectrodes at the bottom of the channel and a transparent electrode plate
      placed at the top. The location of the trap is dependent on the configuration of
      voltages on the array and therefore is addressable. Flowing particles are first
      directed and focused into a single particle stream by the focusing unit. The
      streamed particles are then sorted into different fractions using the movable
      trap by rapidly switching the applied voltage. The performance of the sorter is
      demonstrated by successfully sorting microparticles in a continuous flow. The
      proposed DEP-based microfluidic sorter can be implemented in applications such as
      sample preparation and cell sorting for subsequent analytical processing, where
      sorting of particles is needed.

PMID- 22849063
TI  - Microwave absorption of gamma'-Fe2.6 Ni1.4N nanoparticles derived from nitriding
      counterpart precursor.
AB  - Gamma-Fe2.6Ni1.4 nanoparticles were prepared by the arc-discharge method as the
      precursor and its nitride counterpart of gamma'-Fe2.6Ni14N nanoparticles was
      synthesized directly through a thermal ammonolysis reaction at the temperature of
      673 K for two hours. The resultant product was identified as a homogeneous
      ternary nitride with nearly spherical shape and average size of about 60.0 nm.
      The electromagnetic characteristics of gamma'-Fe2.6Ni1.4N derivant and gamma
      Fe2.6Ni1.4 precursor have been studied in the frequency range of 2-18 GHz.
      Compared with the precursor, gamma'-Fe2.6Ni1.4N nanoparticles exhibits an
      enhanced electromagnetic absorption property resulted from the increased
      dielectric loss by nitriding process. The optimal reflection loss (RL) of gamma'
      Fe2.6Ni1.4N nanoparticles/paraffin composite can reach -39.9 dB at 5.2 GHz in a
      thickness of 2.29 mm, and the frequency band corresponding RL < -10 dB is over
      2.6-18 GHz in the thickness range of 0.78-4.20 mm.

PMID- 22849064
TI  - Synthesis, magnetic properties and catalytic activity of hierarchical cobalt
      microflowers.
AB  - A simple one pot synthesis method for the silver catalyzed growth of pure
      hexagonal close packed cobalt by the reduction of cobalt salt using hydrazine
      hydrate in the presence of triethanolamine (TEA), diethanolamine (DEA) and
      ethylene glycol (EG) as capping agents at 90 degrees C within 10 min has been
      reported. Scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM) images of the product prepared in the presence of capping agents show the
      formation of the well defined porous flowery architecture originating from the
      interlinked 2D wavy nanoflakes. When the same reaction is performed in the
      absence of any capping agent, the agglomeration of the flakes of cobalt with
      irregular spherical morphology is observed. The effect of the reaction conditions
      on the size and the shape of the products have also been studied. Vibration
      sample magnetometer (VSM) shows, that the products are ferromagnetic in nature
      irrespective of the capping agents used and possess high value of coercivity,
      when prepared in the absence of any capping agent. These cobalt microflowers have
      also been proved as an alternative to the other available expensive catalysts
      (Au, Ag, Pt) in the room temperature production of p-aminophenol for its
      applications in pharmaceutical, photographic and plastic industries.

PMID- 22849065
TI  - Enhanced performance of TiO2 nanoparticle and aerogel composite electrode for dye
      sensitized solar cell.
AB  - To evaluate the effects of specific surface area to the photocurrent conversion
      efficiency of dye-sensitized solar cell (DSC), we adopted TiO2 aerogel
      (TA)/nanoparticle (TP) composite as a photoelectrode. We prepared three types of
      photoelectrodes, TPs, TAs, and TATPs (1:1 TAs and TPs composite photoelectrode).
      The performance of TATP composite electrode was compared with that of TP and TAs.
      TATPs showed the improved cell efficiency, more than 0.5%, compared with a
      reference TPs below 15 micrometer thickness. Although the introduction of TAs
      increases the specific surface area for the dye adsorption, DSC composed of only
      TAs does not show the best efficiency result due to the crack generation. In
      conclusion, to produce the best photocurrent conversion efficiency, the high
      specific surface area of TiO2 photoelectrode for high dye adsorption should be
      balanced with proper control of the good electron transfer path.

PMID- 22849066
TI  - Free-standing graphene oxide-poly(vinyl alcohol) membranes self-assembled at
      liquid/air interface.
AB  - Graphene-based composites are appealing as a new class of materials that hold
      great promise for many applications. In this paper, highly ordered, homogeneous
      graphene oxide-poly(vinyl alcohol) (GO-PVA) with different content of PVA
      membranes and reduced graphene oxide-poly(vinyl alcohol) (RGO-PVA) membrane at
      75% loading of PVA in the presence of hydrazine hydrate solution are prepared by
      the self-assemble process at liquid/air interface. The as-prepared membranes were
      investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction
      (XRD), thermal gravimetric analysis (TGA), transmission electron microscopy
      (TEM), Ultraviolet-visible (UV-vis) spectroscopy and four-probe resistance
      measurements. It was shown that the free-standing GO-PVA and RGO-PVA membranes
      are thickness controlled and area adjustable. The GO-PVA membranes have excellent
      transparent. The electrical conductivity of RGO-PVA membranes was up to 0.6 S/m
      by the chemical reduction of hydrazine hydrate. The membranes would be promising
      for practical applications in future nanotechnology.

PMID- 22849067
TI  - Hierarchical structured TiO2 photoanodes for dye-sensitized solar cells.
AB  - A novel approach has been developed to fabricate hills-like hierarchical
      structured TiO2 photoanodes for dye-sensitized solar cells (DSSCs). The
      appropriately aggregated TiO2 clusters in the photoanode layer could cause
      stronger light scattering and higher dye loading that increases the efficiency of
      photovoltaic device. For detailed light-harvesting study, different molecular
      weights of polyvinyl alcohol (PVA) were used as binders for TiO2 nanoparticles (P
      25 Degussa) aggregation. A series of TiO2 films with dissimilar morphology, the
      reflection of TiO2 films, absorbance of attached dye, amount of dye loading, and
      performance of fabricated DSSC devices, were measured and investigated. An
      optimized device had energy conversion efficiency of 4.47% having a higher dye
      loading and good light harvesting, achieving a 23% increase of short-circuit
      current J(sc) in DSSCs.

PMID- 22849068
TI  - Self-assembled diphenylalanine nanowires for cellular studies and sensor
      applications.
AB  - In this paper we present a series of experiments showing that vertical self
      assembled diphenylalanine peptide nanowires (PNWs) are a suitable candidate
      material for cellular biosensing. We grew HeLa and PC12 cells onto PNW modified
      gold surfaces and observed no hindrance of cell growth caused by the peptide
      nanostructures; furthermore we studied the properties of PNWs by investigating
      their influence on the electrochemical behavior of gold electrodes. The PNWs were
      functionalized with polypyrrole (PPy) by chemical polymerization, therefore
      creating conducting peptide/polymer nanowire structures vertically attached to a
      metal electrode. The electroactivity of such structures was characterized by
      cyclic voltammetry. The PNW/PPy modified electrodes were finally used as
      amperometric dopamine sensors, yielding a detection limit of 3,1 microM.

PMID- 22849069
TI  - Chemical functionalization of nanodiamond by amino groups: an X-ray photoelectron
      spectroscopy study.
AB  - The development of chemical functionalization techniques for diamond
      nanocrystallites opens up ways with a view to altering their solubility in
      different solvents, improve interfacial adhesion of nanodiamonds with a composite
      matrix in new materials, and provide new possibilities for the modification of
      the electronic properties of nanodiamond crystallites. In this work, we present
      results on the chemical functionalization of nanodiamonds by amino groups using
      ammonia as a nitrogenation agent. Nanodiamond material used was formed by the
      detonation technique with average crystallite sizes of 4-5 nm. The final
      materials and intermediates products were characterized by Fourier transform
      infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Chemical
      functionalization of nanodiamonds by amino groups could enable the preparation of
      new nylon nano-composite materials. Presence of surface amino groups could alter
      pH of nanodiamond colloids towards basic values and improve colloidal stability
      of nanodiamond suspensions at pH close to 7. This could enable syntheses of new
      drug delivery systems based on nanodiamonds.

PMID- 22849070
TI  - Modification of fullerene nanocolumn structure by accelerated C60 ions.
AB  - Crystalline C60 and amorphous graphite-like films of nanocolumn arrays fabricated
      by glancing angle deposition of C60 fullerene at substrate temperatures of -425 K
      were studied by transmission electron microscopy (TEM) and atomic-force
      microscopy (AFM). Characteristic dimension of columns is 200-400 nm. We used co
      deposition of C60 molecules and accelerated C60 ions to modify the structure and
      properties of nanocolumn arrays. Influence of incidence angle for C60 ions on
      formation of film morphology was revealed. Raman spectrum analysis showed that
      amorphous carbon nanocolumns consist of nanographite areas with average size of 
      1.5 nm. The films have high conductivity (close to graphite) and have no
      mechanical stresses. The carbon films were applied in all-solid-state
      rechargeable thin-film battery as an anode layer. The nanocolumn amorphous carbon
      film as anode electrode showed the discharge capacity of about 50 microAh cm(
      2)microm(-1) and good cycling ability over 100 times in full cell system.

PMID- 22849071
TI  - Growth mechanism and elemental distribution of beta-Ga2O3 crystalline nanowires
      synthesized by cobalt-assisted chemical vapor deposition.
AB  - Long beta-Ga2O3 crystalline nanowires are synthesized on patterned silicon
      substrates using chemical vapor deposition technique. Advanced electron
      microscopy indicates that the as-grown beta-Ga2O3 nanowires are consisted of poly
      crystalline (Co, Ga)O tips and straight crystalline beta-Ga2O3 stems. The
      catalytic cobalt not only locates at the nanowire tips but diffuses into beta
      Ga2O3 nanowire stems several ten nanometers. A solid diffusion growth mechanism
      is proposed based on the spatial elemental distribution along the beta-Ga2O3
      nanowires at nanoscale.

PMID- 22849072
TI  - Surfactant-induced defects and photoluminescence of Co doped SnO2 nanorods.
AB  - The microstructure and defect evolution of Co-doped SnO2 nanostructures have been
      mediated by the surfactant via a hydrothermal method. The microstructure is
      characterized by X-ray diffraction and Raman spectra in detail. It is found that
      the density of structural defects considerably increases with the increase of the
      surfactant amount used in the preparation process. Meanwhile, the orange emission
      enhances dramatically. The growth process and defect evolution have been
      investigated by the following time-dependent experiments. Due to the existence of
      hollow scrolls in the growth, the mesocrystal lamellar attachment and the rolling
      process are proposed for the possible growth mechanism. In the synthetic process,
      surfactant cations, which are incorporated into the network of the self-assembled
      structure, strongly interact with tin hydroxyl anions. After removing the
      surfactants by calcination, the vacancies create in the corresponding locations,
      which promote the orange emission. Our finding opens a new way to control SnO2
      defects and strength the optical emission.

PMID- 22849073
TI  - Analysis and optimization of silver nanoparticles laser synthesis with emission
      spectroscopy of induced plasma.
AB  - Emission spectroscopy of the laser induced plasma is used to characterize the
      laser synthesis of silver nanoparticles in water via attributing the
      thermodynamic parameters of the plasma plume to qualitative features of the
      synthesized nanoparticles. In this approach, effects of the pulse energy and
      frequency of a pulsedNd:YAGlaser on nanoparticles synthesis yield and size
      distribution is studied by an analysis on the behavior of electron temperature
      and total density of the plasma dominant species (neutral Ag atoms; AgI).
      Variation of these thermodynamic parameters obtained from the time-integrated
      emission spectroscopy of the induced plasma was found to be in a closed
      correlation with the mentioned characteristics of the synthesized nanoparticles.
      Assessment of the qualitative features of nanoparticles was performed by
      evaluating the particles concentration in liquid, optical absorption spectroscopy
      and transmission electron microscopy. Finally, the optimum operating conditions
      for the synthesis of silver nanoparticles in pure water is determined by
      summarizing the results of emission spectroscopy observations attributed to the
      mentioned characteristics of synthesized nanoparticles.

PMID- 22849074
TI  - Growth parameter dependent structural and optical properties of ZnO
      nanostructures on Si substrate by a two-zone thermal CVD.
AB  - We investigated the effect of growth parameters on the structural and optical
      properties of the ZnO nanostructures (NSs) grown on Au-coated Si substrate by a
      two-zone thermal chemical vapor deposition. The morphologies of ZnO NSs were
      controlled by various growth parameters, such as growth temperature, O2 flow
      rate, and working pressure, for different thicknesses of Au layer. The nanorod
      like ZnO NSs were formed at 915 degrees C and the growth of two-dimensional
      structures, i.e., nanosheets, was enhanced with the increase of growth
      temperature up to 965 degrees C. It was found that the low working pressure
      contributed to improvement in vertical alignment and uniformity of ZnO NSs. The
      Zn/O atomic % ratio, which plays a key role in the growth mechanism of ZnO NSs,
      was changed by the growth parameters. The Zn/O atomic % ratio was increased with
      increasing the growth temperature, while it was decreased with increasing the
      working pressure. Under proper O2 flow rate, the ZnO nanorods with good
      crystallinity were fabricated with a Zn/O atomic % ratio of -0.9. For various
      growth parameters, the photoluminescence emission was slightly shifted with the
      ultraviolet emission related to the near band edge transition.

PMID- 22849075
TI  - In-situ fabrication of AAO template without oxide barrier layer and its
      applications.
AB  - Porous anodic aluminum oxide (AAO) film is the most widely used template in
      combination with electrodeposition (ED) method to fabricate one-dimensional
      nanostructures such as nanowires, nanotubes and nanorods. However, the existing
      oxide barrier layer after the anodization blocks the application of AAO template
      in synthesis of nanostructures via direct electrodeposition. In this paper, AAO
      template without oxide barrier layer was successfully fabricated by stepwise
      voltage decrement; influence of two types of stepwise voltage decrement on the
      removal of oxide barrier layer was introduced. Field Emission Scanning Electron
      Microscopy (FESEM) images indicated that stepwise voltage decrement could make
      the oxide layer thin effectively. Meanwhile, highly ordered gold nanowire arrays
      were fabricated by using direct electrodeposition method based on AAO template
      with the second anodization process with stepwise voltage decrement of 1 V/min,
      FESEM image showed that as-prepared gold nanowires are uniform in diameter and
      the diameter is in accordance with the diameter of AAO template pores. XRD
      pattern revealed that gold nanowires were indexed as face-centered cubic phase.

PMID- 22849076
TI  - Deposition of ZnO nanoparticles on calcite and studies on their optical
      properties and photocatalytic activity.
AB  - ZnO nanoparticles have been deposited on calcite via a simple chemical method and
      their optical properties and photocatalytic activity have been investigated. The
      ZnO nanoparticles were deposited on calcite by pre-treatment of the calcite
      surface with zinc acetate followed by ZnO deposition. Pre-treatment of the
      calcite was found to be necessary for the uniform deposition of ZnO
      nanoparticles. Various deposition parameters such as concentration of the
      reagents and deposition time were investigated. Diffuse reflectance spectroscopy
      studies indicate that the ZnO nanoparticles on calcite exhibit quantum size
      effect. Room temperature photoluminescence spectra of the samples show the near
      band edge emission due to ZnO nanoparticles and also the emission due to defect
      centers. Photocatalytic degradation of Rhodamine-B was carried out using the ZnO
      nanoparticles deposited calcite and the performance is comparable with that of
      free ZnO nanoparticles.

PMID- 22849077
TI  - Gamma-radiation synthesis of nano/micrometer-scale single-crystalline large gold
      plates.
AB  - An original solution phase approach was developed for the synthesis of single
      crystal Au nanoprims with anisotropic structure of triangular, hexagonal and
      truncated triangular, nanometre or micrometer scale, and nanometer thickness. It
      has been confirmed that the Fe3O4 magnetite nanoparticles and (3-aminopropyl)
      triethoxysilane (APTES) coated on the magnetite nanoparticles play important
      roles in the formation of Au nanoplates. Significantly, such Au nanoplates
      exhibit remarkable optical properties, both the dipole plasmon resonance and the
      quadrupole plasmon resonance were observed. And the selected area electron
      diffraction (SAED) pattern shows the nanoplates obtained were single crystals
      with (111) plans as two basal surfaces. The growth of gold nanoplates in the
      solution with time had been monitored by microscopic and spectroscopic techniques
      to allow the detection of several key intermediates in the growth process. To our
      knowledge, this is the first report on the production of large planar gold
      nanostructures with gamma irradiation in combination of another nanocomposite
      materials (APTES-Fe3O4).

PMID- 22849078
TI  - Facile sonochemical synthesis of hierarchical porous CuO nanotablets.
AB  - Hierarchical semiconductor CuO nanotablets with pores have been fabricated on a
      large scale by a facile and one-pot sonochemical process using the copper acetate
      and ammonia aqueous solution as precursor in the absence of surfactants or
      additives. The as-synthesized products were characterized by X-ray diffraction
      (XRD), field emission scanning electron microscope (FESEM), transmission electron
      microscope (TEM), high resolution transmission electron microscope (HRTEM),
      selected area electron diffraction (SAED), and N2 physisorption. The results
      reveal that porous tablet-shaped CuO nanostructures composed of nanoribbons
      possess a monoclinc phase CuO with the average diameters about 200 nm and around
      50 nm in thickness. The Brunnauer-Emmett-Teller (BET) specific surface area and
      the single point adsorption total pore volume were measured to be 26.8 m2/g and
      0.083 cm3/g, respectively. The band-gap energies were estimated to be 2.52 eV
      from a UV-vis absorption spectrum, which showed the quantum size effects of the
      nanosized semiconductors. A possible mechanism for porous CuO nanotablets was
      discussed.

PMID- 22849080
TI  - Chirality-dependent anisotropic elastic properties of a monolayer graphene
      nanosheet.
AB  - An analytical approach is presented to predict the elastic properties of a
      monolayer graphene nanosheet based on interatomic potential energy and continuum
      mechanics. The elastic extension and torsional springs are utilized to simulate
      the stretching and angle variation of carbon-carbon bond, respectively. The
      constitutive equation of the graphene nanosheet is derived by using the strain
      energy density, and the analytical formulations for nonzero elastic constants are
      obtained. The in-plane elastic properties of the monolayer graphene nanosheet are
      proved to be anisotropic. In addition, Young's moduli, Poisson's ratios and shear
      modulus of the monolayer graphene nanosheet are calculated according to the force
      constants derived from Morse potential and AMBER force field, respectively, and
      they were proved to be chirality-dependent. The comparison with experimental
      results shows a very agreement.

PMID- 22849079
TI  - Temperature and pressure-mediated structural transition of ZnS nanoparticles.
AB  - We demonstrate that the structural transition of ZnS nanoparticles from
      sphalerite to wurtzite is influenced by high pressures and temperatures. Under
      the pressure of 1 GPa, the structural transition of ZnS nanoparticles commences
      at 250 degrees C, much lower than that 400-500 degrees C for ZnS nanoparticles
      under normal pressures. With the increase of the annealing temperature, the
      transition is enhanced then inhibited with a maximum transition fraction of 14%
      at 300 degrees C and disappears at 500 degrees C. At the annealing temperature of
      300 degrees C, the structural transition of ZnS nanoparticles keeps almost
      invariable with the increase of the pressure from 0.6 GPa to 1 GPa. The mechanism
      for the phenomenon is discussed.

PMID- 22849081
TI  - Synergy derived by combining graphene and carbon nanotubes as nanofillers in
      composites.
AB  - Both one-dimensional carbon nanotubes as well as two-dimensional graphene sheets
      have been extensively investigated as nanofillers in composites. However there
      are very few reports on their combined use in composite materials. Here we report
      the mechanical properties including Young's modulus, tensile strength and fatigue
      properties of an epoxy polymer reinforced with various combinations of graphene
      and carbon nanotube fillers- i.e., nanotubes alone, graphene alone and a mixture
      of graphene and nanotubes. We find that at low nanofillers loadings (< 0.1%
      weight), the graphene fillers performed better than both singlewalled as well as
      multiwalled carbon nanotubes. However, interestingly it was the combination of
      carbon nanotubes with graphene that yielded the greatest improvement in
      mechanical properties. Optical microscopy of thin micro-tomed slices of the
      composites indicated that in the presence of the nanotubes the graphene sheets
      appear to have aggregated into chains forming a network structure. Such long
      range ordering of the nanofillers is very unusual in a nanocomposite system and
      is likely responsible for the enhanced mechanical properties.

PMID- 22849082
TI  - Visible light photoelectrochemical performance of W-loaded TiO2 nanotube arrays:
      structural properties.
AB  - Well aligned TiO2 nanotubes were successfully synthesized by anodization of Ti
      foil at 60 V in a fluorinated bath comprised of ethylene glycol with 5 wt% of
      NH4F and 5 wt% of H2O2. In order to enhance the visible light absorption and
      photoelectrochemical response of pure TiO2 nanotube arrays, a mixed oxide system
      (W-TiO2) was investigated. W-TiO2 nanotube arrays were prepared using radio
      frequency (RF) sputtering to incorporate the W into the lattice of TiO2 nanotube
      arrays. The W atoms occupy the substitutional position within the vacancies of
      TiO2 nanotube arrays. The as-anodized TiO2 is amorphous in nature while the
      annealed TiO2 is anatase phase. The mixed oxide (W-TiO2) system in suitable TiO2
      phase plays important roles in efficient electron transfers due to the reduction
      in electron-hole recombination. In this article, the effect of the sputtered W
      into the as-anodized/annealed TiO2 nanotube arrays on the photoelectrochemical
      response was presented.

PMID- 22849083
TI  - Size effects on the stabilization and growth of tetragonal ZrO2 crystallites in a
      nanotubular structure.
AB  - The size effects on the stabilization of ZrO2 polymorphs in nanoscale and the
      growth behavior of their crystallites in 1-D nanotubular structures were
      investigated. Polycrystalline nanotubular structures of ZrO2 with tetragonal
      nanocrystallites were fabricated using nanoporous polycarbonate (PC) templates
      and atomic layer deposition (ALD). The as-prepared ZrO2 nanotubes showed
      polycrystalline structures of stabilized tetragonal polymorphs at room
      temperature. The wall thickness of the ZrO2 nanotubes was well controlled by the
      number of ALD cycles. Faster growth of the tetragonal nanocrystallites was
      observed in the nanotubes with a 50 nm outer diameter, than those of 200 nm. The
      Gibbs-Thompson relation can be used to explain the observed nanosize effects on
      the growth of the tetragonal ZrO2 nanocrystallites.

PMID- 22849084
TI  - Surface patterning of glass via electrostatic imprinting using a platinum mold.
AB  - Electrostatic imprinting is a highly suitable process for patterning large area
      and high efficiency glasses because it enables glass patterning at low
      temperatures with low pressures. Because high DC voltage bias is applied to the
      mold and glass during the thermal imprinting, the mold materials should have
      electrical conductivity, appropriate glass adhesion properties, and excellent
      thermal and electrochemical stability. In this study, thin Pt/Ni molds were
      fabricated via Si micromachining and electroforming techniques and were then used
      in the electrostatic imprint process in order to evaluate their feasibility as
      molds. Under the investigated process conditions, the pattern transfer to glass
      was accomplished without noticeable degradation of the mold. Furthermore, the
      process parameter effects on replication fidelity and potential defects were
      investigated.

PMID- 22849085
TI  - Interface analysis of embedded chip resistor device package and its effect on
      drop shock reliability.
AB  - In this study, the drop reliability of an embedded passive package is
      investigated under JESD22-B111 condition. Chip resistors were buried in a PCB
      board, and it was electrically interconnected by electroless and electrolytic
      copper plating on a tin pad of a chip resistor without intermetallic phase.
      However tin, nickel, and copper formed a complex intermetallic phase, such as
      (Cu, Ni)6Sn5, (Cu, Ni)3Sn, and (Ni, Cu)3Sn2, at the via interface and via wall
      after reflow and aging. Since the amount of the tin layer was small compared with
      the solder joint, excessive intermetallic layer growth was not observed during
      thermal aging. Drop failures are always initiated at the IMC interface, and as
      aging time increases Cu-Sn-Ni IMC phases are transformed continuously due to Cu
      diffusion. We studied the intermetallic formation of the Cu via interface and
      simulated the stress distribution of drop shock by using material properties and
      board structure of embedded passive boards. The drop simulation was conducted
      according to the JEDEC standard. It was revealed that the crack starting point
      related to failure fracture changed due to intermetallic phase transformation
      along the via interface, and the position where failure occurs experimentally
      agrees well with our simulation results.

PMID- 22849086
TI  - Chemical-mechanical planarization aided dimple etching for self alignment.
AB  - Through silicon via (TSV) technology is becoming a mainstream method of building
      3-dimensional integrated circuits (3D IC). In particular, TSV Cu CMP is a
      critical process to remove excess Cu and makes a planar surface which requires a
      removal rate higher than 5 microm/min and a dishing lower than 0.3 microm. This
      paper focuses on the development of a new self-alignment method using dimples on
      the TSV Cu back surface. We tried to find an application potential of a bump
      dimple structure for self alignment using a pretest tool of a solder ball array
      structure. Chemical-mechanical planarization (CMP) aided dimple etching is
      carefully studied as a key solution for deep and uniform dimple formation. The
      experiment shows that CMP is an excellent process to generate a clean oxide
      surface and a clear dishing on the Cu TSV, resulting in a seed for etching.
      Finally, etching realizes a uniform dimple depth of 7 microm to 9 microm in spite
      of changes of via diameter from 10 microm to 50 microm after only 15 sec etching.

PMID- 22849087
TI  - Effect of lightly doped drain structure on P-channel metal induced lateral
      crystallization thin film transistors.
AB  - A Lightly Doped Drain (LDD) structure is known to be very effective in preventing
      hot electrons in modern NMOS transistors. In this work, the lightly doped region
      was formed in poly TFT by using a separate LDD mask aligned to a gate mask. The
      misalignment can be calculated to be about 1.5 microm, and depending on the
      location of the V(d) application between the source and drain, an LDD or Lightly
      Doped Source (LDS) structure can be realized on the same TFT. In this way, we can
      make a perfect comparison between these two structures. It turned out that the
      LDD is mainly responsible for the low leakage current, and no more than 0.5
      microm of the lightly doped region is necessary to lower the leakage current down
      to less than 5 x 10(-11) amps at V(d) = 10 volts. Typically, the on-current of
      MILC TFT is more than 10(-4) amps, but 2.5 microm LDS decreases it to below 10(
      7) amps.

PMID- 22849088
TI  - A study on green organic light-emitting diodes with high electron mobility in
      hole block and electron transport layers.
AB  - The electron mobility and hole blocking ability of BPhen, BCP, and ET137 were
      investigated by fabricating an electron only device and hole only device,
      respectively. Although it was observed that ET137 has the highest electron
      mobility, the device with ET137 as electron transporting layer was unable to
      obtain high efficiency alone and it was necessary to use a hole blocking layer
      because of the poor hole blocking ability due to the high-lying HOMO energy
      level. We fabricated green-emitting phosphorescent devices with various hole
      blocking layers and electron transporting layers. It was demonstrated that the
      high electron mobility of the electron transporting layer and hole blocking layer
      leads to high efficiency in organic light-emitting diodes. The device with BPhen
      and ET137 as hole blocking layer and electron transporting layer, respectively,
      showed the best efficiency properties. The maximum values of luminous efficiency,
      power efficiency, and quantum efficiency were 41.1 cd/A, 26.9 Im/W and 12.4%,
      respectively.

PMID- 22849089
TI  - Inverted polymer solar cells with an ultrathin lithium fluoride buffer layer.
AB  - An ultrathin lithium fluoride (LiF) buffer layer was applied to inverted polymer
      solar cells with P3HT [poly(3-hexylthiophene)]:PCBM [[6,6]-phenyl C61-butyric
      acid methyl ester] blend films. By inserting the LiF layer between the
      transparent electrode and the P3HT:PCBM blend film, all parameters, including the
      short-circuit current, the open-circuit voltage and the fill factor, were
      enhanced compared to those of a reference cell without the LiF layer. The power
      conversion efficiency of the device with the LiF layer was thereby improved by
      more than 300% relative to the reference cell.

PMID- 22849090
TI  - Thermal resistance of light emitting diode PCB with thermal vias.
AB  - Light emitting diodes (LEDs) are already familiar for use as lighting sources in
      various electronic devices and displays. LEDs have many advantages such as long
      life, low power consumption, and high reliability. In the future, as an
      alternative to fluorescent lighting, LEDs are certain to receive much attention.
      However, in components related to advanced LED packages or modules there has been
      an issue regarding the heat from the LED chip. The LED chip is still being
      developed for use in high-power devices which generate more heat. In this study,
      we investigate the variation of thermal resistance in LED modules embedded with
      thermal vias. Through the analysis of thermal resistance with various test
      vehicles, we obtained the concrete relationship between thermal resistance and
      the thermal via structure.

PMID- 22849091
TI  - Modified polyvinyl alcohol layer with hydrophobic surface for the passivation of
      pentacene thin-film transistor.
AB  - We modified the surface of a polyvinyl alcohol (PVA) layer by self assembly
      monolayer technique using a fluorine substituted silane compound (1H,1H,2H,2H
      perfluorooctyl-trichlorosilane: FTS) to protect a pentacene thin-film transistor
      (TFT) from O2 and H2O. Surface modified PVA showed very low surface energy with
      water contact angle of 106.2 degrees. Surface treatment of PVA layer on pentacene
      TFT device was done in toluene solvent and we did not observe any damage to the
      PVA layer or pentacene TFT devices during surface modification process. Pentacene
      TFT with surface modified PVA passivation layer exhibited very stable TFT
      operation with almost no field effect mobility drop or threshold voltage shift up
      to 400 hrs. The performance of unpassivated OTFTs exponentially degraded and
      almost failed in 290 hrs. We propose that modified PVA layer can be used as a
      good passivation layer for oxygen and water in OTFT.

PMID- 22849092
TI  - Electrochemical migration characteristics of screen-printed silver patterns on FR
      4 substrate.
AB  - We evaluated the electrical reliability of screen-printed silver (Ag) patterns
      sintered at various temperatures under variable bias voltages. Comb-type patterns
      were screen-printed onto a flame resistance-4 substrate using a commercial Ag
      nanopaste (24 nm in diameter, 73 wt% of Ag nanoparticles). The printed patterns
      were then sintered for 30 min in air at various temperatures ranging from 100
      degrees C to 200 degrees C. The microstructures and thickness profiles of the
      sintered conductive patterns were identified with a field emission scanning
      electron microscope and a 3-D surface profiler, respectively. In this study, the
      phenomenon of electrochemical migration was investigated with a water drop test
      with deionized water. These results showed that the time required by dendrites to
      bridge from a cathode to an anode was affected by the sintering temperature and
      applied voltage; when the sintering temperature was 200 degrees C, the time to
      achieve a short circuit was nearly four times that of the sample sintered at 100
      degrees C, and while the applied voltage increased from 3 V to 9 V, the time to
      reach a short circuit decreased, on average, by 11%.

PMID- 22849094
TI  - Spectroscopic ellipsometry analysis of amorphous silicon thin films for Si
      nanocrystals.
AB  - Hydrogenated amorphous and nano-crocrystalline silicon thin films were grown by
      very-high-frequency plasma-enhanced chemical vapor deposition (VHF-PECVD, 60
      MHz). In this paper, we report the defects of nano-crystallites embedded in an
      amorphous matrix of hydrogenated silicon alloy (a-Si:H) thin film as investigated
      by spectroscopic ellipsometry (SE). The peak intensity and position of the
      imaginary part of the dielectric constant (epsilon2) as a function of the energy
      show various material states, including a-Si:H (3.5 eV) and nc-Si (4.2 eV), along
      with the absorption coefficient, thickness, optical gap, and the characteristics
      of the defects. The ratio of the characteristic Raman features, the TA/LO and
      LA/LO ratio, is related to the defect states in the films. It was correlated to
      the SE data. Following this, we look into the systematic change in the
      crystallinity of the film from the SE results. Quantized crystallinity values
      from the SE data show good agreement by more than 88.75% with the crystallinity
      information obtained through Raman spectroscopy.

PMID- 22849093
TI  - An efficient ray tracing algorithm for the simulation of light trapping effects
      in Si solar cells with textured surfaces.
AB  - Optimizing the design of the surface texture is an essential aspect of Si solar
      cell technology as it can maximize the light trapping efficiency of the cells.
      The proper simulation tools can provide efficient means of designing and
      analyzing the effects of the texture patterns on light confinement in an active
      medium. In this work, a newly devised algorithm termed Slab-Outline, based on a
      ray tracing technique, is reported. The details of the intersection searching
      logic adopted in Slab-Outline algorithm are also discussed. The efficiency of the
      logic was tested by comparing the computing time between the current algorithm
      and the Constructive Solid Geometry algorithm, and its superiority in computing
      speed was proved. The validity of the new algorithm was verified by comparing the
      simulated reflectance spectra with the measured spectra from a textured Si
      surface.

PMID- 22849095
TI  - Formation of silicon sheet on a rotating substrate.
AB  - A spin casting process to fabricate polycrystalline silicon sheets for use as
      solar cell wafers is presented and the parameters that control the sheet
      thickness are investigated. The computational model for the spin casting is
      proposed in order to understand the melt flow and solidification behaviors in the
      mold. The effect of the rotating speed of the mold and substrate morphology on
      the silicon sheets is studied via computer simulations, and the simulation
      results are compared with the experimental results. The numerical study of the
      fluidity and solidification behavior of the silicon predicted that the formation
      of rectangular sheets via spin casting is feasible, and the subsequent experiment
      confirmed this prediction. Using a square mold, rectangular silicon sheets can be
      produced under appropriate experimental conditions. Microstructural analyses
      verified the presence of long columnar structures on the sheets.

PMID- 22849096
TI  - Extreme pressure properties of multi-component oil-based nanofluids.
AB  - Multi-component oil-based nanofluids were prepared by dispersing two different
      carbons and silver nanoparticles in lubricating oil; then, their tribological
      properties were investigated using a four-ball tribotester and FZG machine. Each
      nanofluid demonstrated excellent wear resistance or extreme pressure (EP)
      properties, but not both properties simultaneously. Therefore, a new concept of a
      mixed nanofluid was developed to satisfy the wear and EP properties. The multi
      component mixed nanofluids containing graphite and Ag nanoparticles not only
      demonstrated enhanced load carrying and anti-wear properties, but also reduced
      the electric power consumption by more than 4.8% compared with the base oil in
      the FZG test.

PMID- 22849097
TI  - Growth of spin-capable multi-walled carbon nanotubes and flexible transparent
      sheet films.
AB  - Iron-catalyzed spin-capable multi-walled carbon nanotubes (MWCNTs) were grown on
      a SiO2 wafer by chemical vapor deposition, which was carried out at 780 degrees C
      using C2H2 and H2 gases. We fabricated a flexible transparent film using the spun
      MWCNTs. The MWCNT sheets were produced by being continuously pulled out from well
      aligned MWCNTs grown on a substrate. The MWCNT sheet films were manufactured by
      simply carrying out direct coating on a flexible film or glass. The thickness of
      the sheet film decreased remarkably when alcohol was sprayed on the surface of
      the sheet. The alcohol spraying increased the transmittance and decreased the
      electrical resistance of the MWCNT sheet films. The sheets obtained after alcohol
      spraying had a resistance of -699 omega and a transmittance of 81%-85%. The MWCNT
      sheet films were heated by applying direct current. The transparent heaters
      showed a rapid thermal response and uniform distribution of temperature. In
      addition, we tested the field emission of the sheet films. The sheet films showed
      a turn-on voltage of -1.45 V/microm during field emission.

PMID- 22849098
TI  - Co-sedimentation of TiO2 nanoparticles and polymer beads to fabricate macroporous
      TiO2 photoelectrodes.
AB  - Dye-sensitized solar cells based on highly porous nanocrystalline TiO2 films have
      drawn considerable attention due to their high conversion efficiency and low
      production cost. TiO2 nanocrystalline electrodes have been investigated
      extensively as a key material. In this study, we discuss dye-sensitized solar
      cells based on macroporous TiO2 films using a highly-dispersed aqueous solution
      of TiO2 nanoparticles and polymeric particles. After drying this solution on the
      conducting glass substrate, the sacrificial polymer particles were removed
      selectively by thermal sintering at high temperatures over 400 degrees C or
      chemical treatment at the low temperature of 150 degrees C. This method provides
      the flexible control of TiO2 fractions or pore size or fabrication temperature.
      Also highly-dispersed TiO2 particles with a high crystallinity would provide a
      promising solution on low-temperature process for flexible DSSCs.

PMID- 22849099
TI  - Low-power and controllable memory window in Pt/Pr0.7Ca0.3MnO3/yttria-stabilized
      zirconia/W resistive random-access memory devices.
AB  - Yttria-stabilized zirconia (YSZ) layers of various thicknesses were designed and
      introduced before Pr0.7Ca0.3MnO3 (PCMO) film was deposited on W bottom electrodes
      with a submicron via-hole structure. By changing the thickness of the YSZ barrier
      layer (3, 5, 9, and 13 nm), a tunable memory window can be realized while low
      power consumption (P(max) < 4 microW) is maintained. Resistive switching (RS) in
      a Pt/PCMO/YSZ/W stack with a thin YSZ layer can be ascribed to an
      oxidation/reduction reaction caused by a ring-type PCMO/W contact, while RS with
      a thick YSZ layer may be related to oxygen migration across the YSZ layer between
      the PCMO film and the W bottom electrode and the increase (decrease) of the
      effective tunnel barrier height of the YSZ layer. Excellent RS behavior
      characteristics, such as a large R(HRS)/R(LRS) ratio (> 10(3)), die-to-die
      uniformity, sweeping endurance, and a retention time of more than 10(3) s, can be
      obtained by optimizing the thickness of YSZ layer.

PMID- 22849100
TI  - Extreme ultra-violet resists development concepts and performances.
AB  - Recently published experimental results indicate that current extreme ultra
      violet lithography (EUVL) patterning process seems to be very hard to meet the
      device manufacturing specification goals, such as resolution, line-width
      roughness, and sensitivity (RLS) simultaneously. To overcome trade-off
      limitations between RLS performances of resist, we have approached the problem in
      several ways. Regarding materials, to make a uniform resist film we applied
      living radical polymerization and purification to obtain evenly interacting
      polymer chains. To obtain perfectly miscible resist components, such as polymer,
      photo acid generator (PAG) and quencher, we have optimized their structures to
      have similar polarity range. Acid diffusivity factors are also controlled by the
      resist components properties, including polymer T(g) and photo-acid polarity. In
      EUVL process, we applied surfactant rinse process to reduce line-width roughness
      and pattern collapse. In this paper, we discuss the performance of our EUV
      according to our material development concepts, that is, resist film homogeneity
      and acid diffusion control in order to meet the device manufacturing
      specification goals, such as resolution, line-width roughness (LWR), and
      sensitivity.

PMID- 22849101
TI  - Ductile fracture mechanism of low-temperature In-48Sn alloy joint under high
      strain rate loading.
AB  - The failure behaviors of In-48Sn solder ball joints under various strain rate
      loadings were investigated with both experimental and finite element modeling
      study. The bonding force of In-48Sn solder on an Ni plated Cu pad increased with
      increasing shear speed, mainly due to the high strain-rate sensitivity of the
      solder alloy. In contrast to the cases of Sn-based Pb-free solder joints, the
      transition of the fracture mode from a ductile mode to a brittle mode was not
      observed in this solder joint system due to the soft nature of the In-48Sn alloy.
      This result is discussed in terms of the relationship between the strain-rate of
      the solder alloy, the work-hardening effect and the resulting stress
      concentration at the interfacial regions.

PMID- 22849102
TI  - Size-dependent electrical conductivity of indium zinc oxide deposited by RF
      magnetron sputtering.
AB  - We investigated the size-dependent electrical conductivities of indium zinc oxide
      stripes with different widths from 50 nm to 4 microm and with the same thickness
      of 50 nm deposited by RF magnetron sputtering. The size of the indium zinc oxide
      stripes was controlled by e-beam lithography. The distance of the two Ti/Au Ohmic
      electrodes along the indium zinc oxide stripes was kept constant at 25 microm.
      The electrical conductivity decreased as the size of the indium zinc oxide
      stripes decreased below a critical width (80 nm). The activation energy, derived
      from the electric conductivity versus temperature measurement, was dependent on
      the dimensions of indium zinc oxide stripes. These results can be understood as
      stemming from surface charge trapping from the absorption of oxygen and/or water
      vapor, which leads to an increase in the energy difference between the conduction
      energy band and the Fermi energy.

PMID- 22849103
TI  - All solution processed organic thin film transistor-backplane with printing
      technology for electrophoretic display.
AB  - In this study, solution processes were developed for backplane using an organic
      thin film transistor (OTFT) as a driving device for an electrophoretic display
      (EPD) panel. The processes covered not only the key device of OTFTs but also
      interlayer and pixel electrodes. The various materials and printing processes
      were adopted to achieve the requirements of devices and functioning layers. The
      performance of OTFT of the backplane was sufficient to drive EPD sheet by
      producing a mobility of 0.12 cm2/v x sec and on/off current ratio of 10(5).

PMID- 22849104
TI  - Effect of curing temperature on nano-silver paste ink for organic thin-film
      transistors.
AB  - Silver (Ag) metal electrode having 20 microm channel length was printed by
      reverse offset printing (ROP) using nano-silver paste ink for the source/drain of
      organic thin-film transistors (OTFT). Specific resistance and surface roughness
      of printed Ag electrodes with increasing curing temperature were investigated,
      and surface morphology and grain growth mechanism were systematically verified
      using a scanning electron microscope (SEM) and atomic force microscope (AFM) in
      order to obtain an optimized ROP Ag electrode. The Ag electrode was applied to
      fabricate top-gate/bottom-contact poly(3-hexylthiophene) OTFT devices, which
      showed reproducible OTFT characteristics such as the field-effect mobility,
      threshold voltage, and an on/off-current ratio of -10(-3) cm2/Vs, 0.36 V, and 
      10(2), respectively.

PMID- 22849105
TI  - Fabrication of color electronic paper display by using the charged particles.
AB  - We fabricated a color electronic paper display (EPD) by using the charged
      particles. The display has 160 (xRGBW) x 480 array of pixels and four inch
      diagonal viewing area. Color filter technology was applied for coloration of the
      EPD. The fabrication process was as follows. First, ITO electrodes were patterned
      on top and bottom substrates. Ribs were formed to define pixels on the bottom
      substrate, and color filters were deposited on the ITO of top substrate. The
      charged particles were put into the pixel arrays defined by the ribs. Finally,
      the top substrate having the color filters was assembled on the bottom substrate.
      The resolution was 160 (xRGBW) x 480 with 4 x 4 inch area. The color gamut was
      about 2.49%, and the response time was 0.25 msec at 90 V. The contrast ratio was
      2.36. The color EPD successfully demonstrated to display some images.

PMID- 22849106
TI  - Diphenylamino-fluorenylethylene derivatives for highly efficient blue organic
      light-emitting diodes.
AB  - Highly efficient blue organic light-emitting diodes (OLEDs) were developed using
      diphenylamino-fluorenylethylene derivatives. In particular, OLEDs using compound
      3 as a dopant in the emitting layer showed a maximum luminance of 12940 cd/m2 at
      10 V; a luminous efficiency of 12.68 cd/A at 20 mA/cm2; a power efficiency of
      5.24 Im/W at 20 mA/cm2, and CIE(x,y) coordinates of 0.181, 0.295 at 10 V.
      Furthermore, a deep blue OLED using dopant 2 with CIE coordinates of (0.154,
      0.129) exhibited a maximum luminance of 5315 cd/m2 at 10 V; a luminous efficiency
      of 4.11 cd/A at 20 mA/cm2, and a power efficiency of 1.66 Im/W at 20 mA/cm2.

PMID- 22849107
TI  - Electrochemical and thermal behaviour of Li[Li(x)(Ni0.3Co0.1Mn0.6)1 - x]O2 (x =
      0.09, 0.11) cathode Materials for lithium rechargeable batteries.
AB  - High rate capable Mn-rich layered Li[Li(x)(Ni0.3Co0.1Mn0.6)1-x]O2 (x = 0.09,
      0.11) cathode materials that are fully charged are investigated with respect to
      stability. Differential scanning calorimetry is used to determine the thermal
      stability of cathode material compositions together with PVdF binder and a
      conductive agent by heating from 30 degrees C to 400 degrees C at 10 degrees
      C/min. In the Li[Li(x)(Ni0.3Co0.1Mn0.6)1-x]O2 (x = 0.09, x = 0.11) cathode
      materials, the exothermic reaction started at 100 degrees C. Due to thermal
      runway, a sharp peak was observed at 279.25 degrees C for the material of x =
      0.09 with exothermic heat generation of 168.4 J/g. For the Mn-rich cathode
      material, where x = 0.11, two relatively smaller peaks appeared at 250.72 degrees
      C and 268.60 degrees C with heat evolution of 71.49 J/g and 93.67 J/g,
      respectively. These layered cathode materials are thermally stable. The x = 0.09
      composition shows huge heat flow occurrence when compared to the x = 0.11. It is
      concluded from a heat generation analysis that the two Mn-rich cathode materials
      are thermally stable for lithium rechargeable batteries.

PMID- 22849108
TI  - Effect of carrier injection stress in thin film solar cells by impedance
      spectroscopy.
AB  - In amorphous silicon solar cells, degradation is directly related to V(oc), FF
      and cell performance. The dependence of the stability of thin film amorphous
      silicon solar cells is studied in terms of the volume fraction of B2H6 in the p
      layer. When the volume fraction of B2H6 is increased by an order of magnitude,
      the doping-induced defects tend to increase quite rapidly. Low-doped p-type a
      SiO(x) layers had better initial properties but rapidly degraded. Heavily doped p
      type a-SiO(x) layers had lower initial properties but displayed better stability.
      The improvement in stability is explained in conjunction with the capacitance and
      resistance values of impedance spectroscopy. When the B2H6 gas flow rate is
      increased, the cell is degraded showing a capacitance decay decrease from 51.75%
      to less than 18.18%. In addition, the increase in the resistance decreased from
      90.90% to 11.73%.

PMID- 22849109
TI  - Thermal modeling and measurement of junctions in photovoltaic packages.
AB  - This study reports the direct thermal observation of the junction temperature and
      determination of the thermal resistance in a commercial solar cell package under
      actual operating conditions. A thermal transient method was the key method that
      was utilized for the thermal characterization of the device. Sunlight directed
      into the solar cell package was found to increase significantly the heat
      generation inside the solar cell package. It was shown that the operation of the
      solar cell package with sunlight of 1 sun resulted in a junction temperature of
      about 113 degrees C. The simulation data were in good agreement with the measured
      values. Detailed thermal performance of the solar cell package was projected
      using a Computational Fluid Dynamics (CFD) method under various operating
      conditions. Thermal resistance was determined under various operating conditions.

PMID- 22849110
TI  - Novel phenothiazine-based organic dyes with a heteroleptic dual-electron-acceptor
      for dye-sensitized solar cells.
AB  - We designed a novel organic dye with a heteroleptic dual-electron acceptor
      (cyanocrylic acid and rhodanine-acetic acid) on each side of a phenothiazine
      based organic dye as a photosensitizer for dye-sensitized solar cells (DSSCs).
      Density functional theory (DFT) and time-dependent density functional theory
      (TDDFT) calculations were used to estimate the photovoltaic properties of the
      dyes, with the findings showing that the organic dyes when used in the
      heteroleptic dual-electron-acceptor type resulted in higher performance than
      their single electron-acceptor and homoleptic dual-electron-acceptor counterparts
      due to the higher molar extinction coefficients and the orientation of the
      adsorbed dye. It was attributed to relatively broad and intense absorption
      spectra in the visible region with the rhodanine-acetic acid moiety and abundant
      electronic coupling with TiO2 of the cyanoacrylic acid anchoring group.

PMID- 22849111
TI  - Enhanced light harvesting from Forst-type resonance energy transfer in the quasi
      solid state dye-sensitized solar cells.
AB  - The demonstrated Forst-type resonance energy transfer (FRET) is demonstrated in
      quasi-solid type dye-sensitized solar cells between organic fluorescence
      materials as an energy donor doped in polymeric gel electrolyte and a ruthenium
      complex as an energy acceptor on the surface of TiO2. Strong spectral overlap of
      emission/absorption of the energy donor and acceptor is required to obtain high
      FRET efficiency. The judicious choice of the energy donor allows the enhancement
      of the light harvesting characters of the energy acceptor (N3) in quasi-solid dye
      sensitized solar cells which increases the power conversion efficiency by 25%
      compare to that of a pristine cell. The optimized cell architecture fabricated
      with the quasi-solid type electrolyte containing fluorescence materials shows a
      maximum efficiency of 5.08% with a short-circuit current density (J(sc)) of 12.63
      mA/cm2, and an open-circuit voltage (V(oc)) of 0.70 V under illumination of
      simulated solar light (AM 1.5, 100 mW/cm2).

PMID- 22849112
TI  - Enhanced electron lifetime on nitrogen-doped TiO2 films for dye-sensitized solar
      cells.
AB  - Nitrogen-doped TiO2 crystallites were prepared via the hydrolysis of TiCl4 using
      an ammonia medium in an aqueous solution for DSSC photoelectrodes. The optimized
      photoelectrode for the DSSC was prepared with 9.4 nm sized N-doped TiO2 crystal
      (BET; 200 m2/g), which provides a relatively high short circuit current and
      energy conversion efficiency in the DSSC. The photovoltaic performance of the N
      doped TiO2 electrode was confirmed using incident photon-to-current efficient
      spectra, impedance analyses, and Bode-phase plots which proved that the N-doped
      TiO2 electrode has a significantly enhanced electron lifetime compared with that
      of the P25 electrode.

PMID- 22849113
TI  - Effects of substrate heating on the photovoltaic characteristics of dye
      sensitized solar cells during two-step Ti film deposition by RF magnetron
      sputtering.
AB  - Nanoporous Ti metal film electrodes for use as photoanodes in dye-sensitized
      solar cells (DSSCs) were deposited directly on the nanoporous TiO2 layer using
      the two-step RF magnetron sputtering technique. The Ti film electrode replaces
      the transparent conducting oxide (TCO) layer. The effect of substrate heating
      during the deposition of the Ti film was studied to improve the porosity and
      columnar array of the film pores and the resulting cell efficiency. The porous Ti
      layer (-41 microm) with low sheet resistance (-1.7 omega/sq) was obtained by
      deposition at 250 degrees C. The porous Ti layer collects electrons from the TiO2
      layer and allows the diffusion of I-/I3(-) through the holes. The DSSC efficiency
      (eta) using porous Ti layers with highly columnar structures was measured with
      the highest conversion efficiency of -5.77%; the other photovoltaic properties
      were ff: 0.76, V(oc): 0.72 V, and J(sc): 10.6 mA/cm2.

PMID- 22849114
TI  - Controlled growth of ZnO nanomaterials via hydrothermal method: effect of buffer
      layer.
AB  - We report a facile solution-based method for the controlled growth of ZnO
      nanomaterials on an AIN/Si substrate. A ZnO buffer layer was coated on the
      substrate before growing the ZnO nano-materials. The shape of the ZnO
      nanomaterials changed from nanosheet to nanorod as the thickness of the ZnO
      buffer layer increased. Doping of the buffer layer with Ga decreased the average
      grain size of the ZnO buffer layer, which resulted in the growth of longer and
      thinner ZnO nanorods on the buffer layer. The UV sensing results of the ZnO
      nanorod-based device revealed that the aspect ratio of the ZnO nanorods is
      crucial for enhancing the performance of the device.

PMID- 22849115
TI  - Preparation of nano-sized graphite-supported CuO and Cu-Sn as active materials in
      lithium ion batteries.
AB  - Nano-sized Cu-Sn and Cu oxide particles supported on ball-milled graphite were
      synthesized, and their electrochemical characteristics for use as anode active
      materials in lithium-ion batteries were investigated. The samples were also
      characterized via FE-SEM, XRD, and TGA. Most of the Cu oxides on BMG were
      monoclinic CuO crystals, whereas the Cu-Sn particles were composed of hexagonal
      Cu3Sn and tetragonal SnO2 crystals. These particles may contribute to an increase
      in the reversible capacity of lithium ion batteries.

PMID- 22849116
TI  - Study on the characteristics of amorphous low-K thin film for solar cells.
AB  - The most practical solar cells are silicon based crystal silicon solar cells.
      Phosphorus oxychloride for n+ type doping was diffused on a p+ Si, SiC and poly
      Si using N2 carrier gas by low pressure chemical vapor deposition. The series
      resistances on various p type silicon substrates were researched. An n(+)-p+
      junction was fabricated by thermal diffusion of phosphorus oxychloride into a p+
      Si wafer. For the rear metallization, Al was deposited using screen printing and
      SiOC film was used instead of SiO2 film as a passivation material for the metal
      layer. SiOC film was made by the capacitive coupled plasma chemical vapor
      deposition. When the Fourier transform infrared spectra of SiOC film shows
      organic properties including a strong peak of the Si-CH3 bond, the efficiency was
      increased, because of the reduction of the recombination at the back surface.

PMID- 22849117
TI  - Electro-optical properties of nano-thickness polymer film.
AB  - We report the electro-optical (E/O) characteristics of the Langmuir-Blodgett film
      of poly(vinylidene fluoride with trifluoroethylene) copolymers. The structural
      origin of E/O response of nano LB films was discussed with the result of
      temperature dependent E/O response at a temperature range from 20 to 100 degrees
      C. Thermal hysteresis of E/O response and the ferroelectric-paraelectric phase
      transition were observed at a 20 monomolecular layers Langmuir-Blodgett films.

PMID- 22849118
TI  - Optical performance of extreme ultraviolet lithography mask with an indium tin
      oxide absorber.
AB  - In this study, we propose a new extreme ultraviolet (EUV) binary mask with an
      indium tin oxide (ITO) absorber. The optical constant of ITO film at 13.5 nm
      wavelength in the EUV regime was determined by means of X-ray reflectivity
      measurements and the chemical composition was determined using Rutherford
      backscattering spectrometry. The reflectance of a binary mask with an ITO
      absorber layer at various thicknesses was also measured to investigate the
      optical performance in the EUV regime. It was found that the extinction
      coefficient of ITO film is higher than that of a typical absorber layer, TaN, and
      that the reflectance of the ITO absorber in the binary mask at a wavelength of
      13.5 nm is reduced to 0.62% at a thickness of 45 nm. Therefore, it is expected
      that the ITO film can be employed as a thin absorber of a binary mask to reduce
      the geometrical shadow effect in extreme ultraviolet lithography.

PMID- 22849119
TI  - Highly selective etching of SnO2 absorber in binary mask structure for extreme
      ultra-violet lithography.
AB  - Among the core EUVL (extreme ultra-violet lithography) technologies for nanoscale
      patterning below the 30 nm node for Si chip manufacturing, new materials and
      fabrication processes for high-performance EUVL masks are of considerable
      importance due to the use of new reflective optics. In this work, the selective
      etching of SnO2 (tin oxide) as a new absorber material, with high EUV absorbance
      due to its large extinction coefficient, for the binary mask structure of SnO2
      (absorber layer)/Ru (capping/etch stop layer)/Mo-Si multilayer (reflective
      layer)/Si (substrate), was investigated. Because infinitely high selectivity of
      the SnO2 layer to the Ru ESL is required due to the ultrathin nature of the Ru
      layer, various etch parameters were assessed in the inductively coupled Cl2/Ar
      plasmas in order to find the process window required for infinitely high etch
      selectivity of the SnO2 layer. The results showed that the gas flow ratio and
      V(dc) value play an important role in determining the process window for the
      infinitely high etch selectivity of SnO2 to Ru ESL. The high EUV-absorbance SnO2
      layer, patternable by a dry process, allows a smaller absorber thickness, which
      can mitigate the geometric shadowing effects observed for high-performance binary
      EUVL masks.

PMID- 22849120
TI  - Characteristics of tin oxide-based thin film transistors prepared by DC magnetron
      sputtering.
AB  - Here we demonstrate the fabrication of SnO(x) thin-film transistors (TFTs), where
      SnO(x) thin films are deposited as an active channel layer by DC magnetron
      sputtering. We analyzed the effects of the oxygen partial pressure ratio and post
      deposition heat treatment (PDHT) on the characteristics of the SnO(x) thin films.
      We found improved performance of the TFTs obtained by using interface
      modification with the optimized deposition condition of SnO(x) thin films. These
      results are helpful for fabricating oxide-TFTs, including simple binary oxide
      semiconductors, as an active channel layer.

PMID- 22849121
TI  - Effect of rapid thermal annealing on the electrical, optical and structural
      properties of ZnO-doped In2O3 films grown by linear facing target sputtering.
AB  - We investigated the effect of rapid thermal annealing on the electrical, optical,
      and structural properties of ZnO-doped In2O3 (ZIO) films grown at different Ar/O2
      flow ratios (15/0 and 15/1 sccm) by using linear facing target sputtering. It was
      found that the ZIO films grown at different Ar/O2, flow ratios showed different
      electrical and optical behavior with increasing rapid thermal annealing
      temperature. Synchrotron X-ray scattering examination showed that the different
      electrical and optical properties of the ZIO films could be attributed to the
      difference in preferred orientation with an increase in rapid thermal annealing
      temperature.

PMID- 22849122
TI  - Microstructure and dielectric characteristics of high-k tetragonal ZrO2 films
      with various thicknesses processed by sol-gel method.
AB  - High-k ZrO2/Si films were fabricated by a sol-gel method and the effects of the
      thickness of ZrO2 on the phase formation, interface chemical structure, and
      dielectric performance were studied. The 0.1 M precursor sol was prepared by
      using Zr acetylacetonate, coated, dried on Si substrates, and finally annealed at
      500 degrees C. The thickness of ZrO2 was varied in the range from 7 to 51 nm by
      repeating the coating and drying sequences. The deposited ZrO2 was amorphous for
      the sample with a thickness of -7 nm, but tetragonal (t-) phases appeared as the
      thickness increased. As the thickness increased, the flat-band voltage and
      hysteresis width in the capacitance-voltage curves increased. The sol-gel
      deposited ZrO2 dielectrics showed a high k value (-33) due to the formation of
      the t-phase, while retaining gate leakage current levels of less than -4.0 x 10(
      5) A/cm2 at 1 MV/cm.

PMID- 22849123
TI  - Low-voltage-driven pentacene thin-film transistors with cross-linked poly(4
      vinylphenol)/high-k Bi55b3O15 hybrid dielectric for phototransistor.
AB  - This paper describes the fabrication of pentacene thin-film transistors (TFTs)
      with an organic/inorganic hybrid gate dielectric, consisting of cross-linked
      poly(4-vinylphenol) (PVP) and Bi5Nb3O15. A 300-nm-thick Bi5Nb3O15 dielectric
      film, grown at room temperature, exhibits a high dielectric constant (high-k)
      value of 40 but has an undesirable interface with organic semiconductors (OSC).
      To form better interfaces with OSC, a cross-linked PVP dielectric was stacked on
      the Bi5Nb3O15 dielectric. It is shown that, with the introduction of a hybrid
      dielectric, our devices not only can be operated at a low voltage (- -5 V) but
      also have improved electrical characteristics and photoresponse, including a
      field-effect mobility of 0.72 cm2/V x s, current sub-threshold slopes of 0.29
      V/decade, and a photoresponse of 4.84 at a gate bias V(G) = 0 V under 100 mW/cm2
      AM 1.5 illumination.

PMID- 22849124
TI  - Pixel-isolation walls of liquid crystal display based on prepolymer containing
      vinyl cinnamate.
AB  - Pixel-isolated liquid crystal (PILC) mode investigated in this work is obtained
      by phase separation induced by the anisotropic photoreaction of a prepolymer
      containing a vinyl cinnamate monomer. It was found that the incorporation of the
      cinnamate monomer was an efficient method for the control of the interfacial
      properties between LC and polymer walls. Polarization-selective photo-curing of
      the prepolymer containing a cinnamate monomer was closely related with the liquid
      crystal orientation at the polymer wall boundary resulting in electro-optical
      performance improvement.

PMID- 22849125
TI  - Sub 50 nm nano-patterns with carbon based spin-on organic hardmask.
AB  - Carbon based spin-on organic hardmask (C-SOH) was used as an imprint resin to
      fabricate sub 50 nm sized patterns. Imprinting of C-SOH was done with a
      polyurethaneacrylate (PUA) stamp. Patternability and etch resistance of the C-SOH
      resin was compared to poly(methyl methacrylate) (PMMA). C-SOH can be patterned at
      the nanosize using imprint lithography and exhibits superior etch resistance,
      especially for F-based plasmas. Due to the poor etch resistance of imprint resin
      such as PMMA, it is seldom used as an etch mask to form nano-structures by
      etching the Si3N4 layer. However, such a nano-structure was able to be formed by
      etching the Si3N4 layer using C-SOH as an etch mask.

PMID- 22849126
TI  - Strong ligand field effects of blue phosphorescent Ir(III) complexes with
      phenylpyrazole and phosphines.
AB  - In the paper, we describe new Ir complexes for achieving efficient blue
      phosphorescence. New blue-emitting mixed-ligand Ir complexes comprising one
      cyclometalating, two phosphines trans to each other such as Ir(dppz)(PPh3)2(H)(L)
      (Ll= Cl, NCMe+, CN), [dppz = 3,5-Diphenylpyrazole] were synthesized and studied
      to tune the phosphorescence wavelength to the deep blue region and to enhance the
      luminescence efficiencies. To gain insight into the factors responsible for the
      emission color change and the variation of luminescence efficiency, we
      investigate the electron-withdrawing capabilities of ancillary ligands using DFT
      and TD-DFT calculations on the ground and excited states of the complexes. To
      achieve deep blue emission and increase the emission efficiency, (1) we
      substitute the phenyl group on the 3-position of the pyrazole ring that lowers
      the triplet energy enough that the quenching channel is not thermally accessible
      and (2) change the ancillary ligands coordinated to iridium atom to phosphine and
      cyano groups known as very strong field ligands. Their inclusion in the
      coordination sphere can increase the HOMO-LUMO gap to achieve the hypsochromic
      shift in emission color and lower the HOMO and LUMO energy level, which causes a
      large d-orbital energy splitting and avoids the quenching effect to improve the
      luminescence efficiency. The maximum emission spectra of Ir(dppz)(PPh3)2(H)(CI)
      and Ir(dppz)(PPh3)2(H)(CN) were in the ranges of 439, 432 nm, respectively.

PMID- 22849127
TI  - Improvement of the tool life of a micro-end mill using nano-sized SiC/Ni
      electroplating method.
AB  - High mechanical properties of a tungsten carbide micro-end-mill tool was achieved
      by extending its tool life by electroplating nano-sized SiC particles (< 100 nm)
      that had a hardness similar to diamond in a nickel-based material. The co
      electroplating method on the surface of the micro-end-mill tool was applied using
      SiC particles and Ni particles. Organic additives (saccharin and ammonium
      chloride) were added in a Watts bath to improve the nickel matrix density in the
      electroplating bath and to smooth the surface of the co-electroplating. The
      morphology of the coated nano-sized SiC particles and the composition were
      measured using Scanning Electron Microscope and Energy Dispersive Spectrometer.
      As the Ni/SiC co-electroplating layer was applied, the hardness and friction
      coefficient improved by 50%. Nano-sized SiC particles with 7 wt% were deposited
      on the surface of the micro-end mill while the Ni matrix was smoothed by adding
      organic additives. The tool life of the Ni/SiC co-electroplating coating on the
      micro-end mill was at least 25% longer than that of the existing micro-end mills
      without Ni/SiC co-electroplating. Thus, nano-sized SiC/Ni coating by
      electroplating significantly improves the mechanical properties of tungsten
      carbide micro-end mills.

PMID- 22849128
TI  - Efficiency enhancement in a-plane InGaN/GaN light emitters with carbon nanotubes.
AB  - This study investigates the coupling modes of a-plane InGaN/GaN mutiquantum wells
      (MQWs) with single-walled carbon nanotubes (SWCNTs). The enhancement of light
      emissions at resonance photon energies can be explained by the surface plasmon
      coupling of the MQW-SWCNT hybrid structure. The photoluminescence (PL)
      enhancement ratios of the indigo (2.90 eV) emission from MQWs with SWCNTs reveal
      three coupling modes at 2.50 eV, 2.97 eV, and 3.42 eV. In addition, the trend of
      the PL intensity ratios and efficiencies corresponds to that of the PL
      enhancement ratios. The PL efficiencies for the green (2.46 eV) and indigo (2.90
      eV) emissions of SWCNT-coated MQWs are 32% and 110% better than the corresponding
      values of uncoated MQWs, respectively. The results show that the MQW-SWCNT hybrid
      structure has the potential to be applied in high-efficiency light emitters in
      the visible and ultraviolet range.

PMID- 22849129
TI  - Dry-spray deposition of TiO2 for a flexible dye-sensitized solar cell (DSSC)
      using a nanoparticle deposition system (NPDS).
AB  - TiO2 powders were deposited on indium tin oxide (ITO) coated polyethylene
      terephthalate (PET) substrates for application to the photoelectrode of a dye
      sensitized solar cell (DSSC). In the conventional DSSC manufacturing process, a
      semiconductor oxide such as TiO2 powder requires a sintering process at higher
      temperature than the glass transition temperature (T(g)) of polymers, and thus
      utilization of flexible polymer substrates in DSSC research has been constrained.
      To overcome this restriction related to sintering, we used a nanoparticle
      deposition system (NPDS) that could produce a thin coating layer through a dry
      spray method under atmospheric pressure at room temperature. The powder was
      sprayed through a slit-type nozzle having a 0.4 x 10 mm2 rectangular outlet. In
      order to determine the deposited TiO2 thickness, five kinds of TiO2 layered
      specimens were prepared, where the specimens have single and double layer
      structures. Deposited powders on the ITO coated PET substrates were observed
      using FE-SEM and a scan profiler The thicker TiO2 photoelectrode with a DSSC
      having a double layer structure showed higher energy efficiency than the single
      layer case. The highest fabricated flexible DSSC displayed a short circuit
      current density J(sc) = 1.99 mA cm(-2), open circuit voltage V(oc) = 0.71 V, and
      energy efficiency eta = 0.94%. These results demonstrate the possibility of
      utilizing the dry-spray method to fabricate a TiO2 layer on flexible polymer
      substrates at room temperature under atmospheric pressure.

PMID- 22849130
TI  - Organic photosensitizers with a heteroleptic dual donor for dye-sensitized solar
      cells.
AB  - Using DFT and TDDFT calculations, we investigated the substitution effect in the
      electronic and optical properties of dye sensitizers with a dual donor composed
      of triphenylamine and/or indoline moieties. Due to replacement with the dual
      donor moieties, the HOMO levels were split into HOMO and HOMO - 1 levels, and the
      bandgaps between the HOMO and LUMO levels decreased, leading to the creation of
      bathochromically extended absorption spectra. Nearly degenerated splitting of the
      HOMO levels resulted from the similarity of the electronic structure between the
      HOMO and the HOMO - 1 levels, delocalized over both dual-donor moieties, when
      replacing the dual donors. It was shown that the additional electron-donating
      group creates an additional absorption band and causes a cascading two-electron
      process aiding the charge separation process. Owing to a more panchromatic
      attribute, easier energy transfer and feasible retardation of the recombination
      between the injected electrons and the electrolyte, it is expected that dyeTI
      will show better performance than the other dyes (dyeT dyeTT and dyeIT) as
      denoted here in terms of the conversion efficiency of dye-sensitized solar cells
      (DSSCs). This work presents the probable benefits of dye sensitizers with dual
      donor moieties and provides insight into the development of more efficient dye
      sensitizers for DSSCs through modification of the Frontier molecular orbitals.

PMID- 22849131
TI  - Characterization of transparent conductive ITO, ITiO, and FTO films for
      application in photoelectrochemical cells.
AB  - Transparent conductive In(2-x)Sn(x)O3 (ITO) and In(2-x)Ti(x)O3 (ITiO) films were
      prepared via RF magnetron sputtering on soda-lime glass substrates at 300 degrees
      C and investigated with respect to their photoelectric conversion performance
      compared with the commercial F:SnO2 (FTO) glass. The near infrared ray
      transmittance of ITiO was highest for wavelengths over 1000 nm compared with
      those of ITO and FTO. Photoelectrochemical cells (PECs) were fabricated using
      ITiO film, ITO film, and FTO glass. The photoelectric conversion efficiency (eta)
      of the PECs samples using ITiO was 5.64%, whereas 2.73% was obtained from the PEC
      samples with ITO, both at 100 mW/cm2 light intensity. The impedance measurement
      was also used to explain the electrochemical performance of the PECs with various
      TCO glasses.

PMID- 22849132
TI  - Enhanced electron transport in mesoporous TiO2 films modified by sol-gel necking
      for dye-sensitized solar cells.
AB  - Mesoporous TiO2 films modified via sol-gel necking were fabricated by dispersing
      Ti tetra-isopropoxide (TTIP; 8 to 16 wt% over TiO2) with TiO2 nanoparticles in
      isopropyl alcohol. The dye-sensitized solar cells (DSSCs) with 13 wt% TTIP
      modified TiO2 film exhibited significantly improved overall energy conversion
      efficiency, despite having less adsorbed dye when compared with DSSCs with
      untreated and TiCl4 post-treated TiO2 films. The improvement can be attributed to
      the sol-gel necking (or interconnection) between the nanoparticles which leads to
      a much faster electron transport and a suppression of the recombination (or back
      electron transfer) between the TiO2 and electrolyte.

PMID- 22849133
TI  - Fabrication of nano silica dispersed permalloy composite coating.
AB  - In aqueous solution, the agglomeration of silica nanopowder is a major problem
      which causes poor uniformity of electroplated surfaces. Silica surface is
      susceptible to moisture due to the hydroxyl group on its surface which causes the
      silica nanopowder to become agglomerated. In this study, silica nanoparticle
      dispersion in the electroplated layer is reported. From zeta potential analysis,
      silica nanopowder has a negatively charged surface in an alkaline bath. Silica
      nanopowder is less agglomerated in an alkaline bath than in an acidic bath due to
      the surface charge. Additives change the surface morphologies of the
      electroplated layer as well as the silica nanopowder contents. Comparing an
      alkaline bath and an acidic bath, the advantage of an additive to the
      electroplated layer is only observed in an alkaline bath. Types of sonicators and
      sonication periods are also surveyed for silica nanopowder dispersion. Sonication
      time can be reduced by a horn-type sonicator, and longer sonication time
      guaranteed better silica nanopowder dispersion.

PMID- 22849134
TI  - Macrodispersion of multi-walled carbon nanotubes for conductive films.
AB  - Understanding of the effect of the multi-walled carbon nanotube (MWCNT)
      dispersion process on physical properties of MWCNT film is crucial in process
      optimization of MWCNT film-based products. In the present work, the electrical
      conduction property of MWCNT films according to various conditions in MWCNT
      dispersion is investigated. Spectroscopic analysis of dispersed MWCNTs show that
      the electrical resistance of the MWCNT conductive film is affected by an increase
      in the electrical contacts between adjacent CNTs due to CNT debundling and
      physical damage caused by ultrasonic processing. Based on the two conflicting
      parameters, dispersion guidelines for highly conductive MWCNT film are presented.

PMID- 22849135
TI  - Directed self-assembly lithography and its application based on simulation
      approach.
AB  - The directed self-assembly (DSA) technology of block copolymers is a candidate
      for next-generation lithography. The computation model of this lithography can
      assist in overcoming its challenges. In this paper, a template-assisted self
      assembly (DSA graphoepitaxy) is modeled and simulated in a molecular scale to
      reduce the process complexity. For a full simulation, the template fabrication
      and DSA process are modeled and simulated to evaluate the impact of the process
      parameters on the pattern profile. Simulation results similar to the experimental
      results allow the prediction of the self-assembled patterns of the confined block
      polymers.

PMID- 22849136
TI  - Fabrication of a polyurethane acrylate/polyimide-based polymer mold for a hot
      embossing process.
AB  - A high-thermal-resistance polymer-based flexible imprint mold was developed to be
      used in a hot embossing process. This mold was readily replicated in a UV curing
      imprint process and can be used as a mold for hot embossing and thermally curing
      imprint processes. The nano-sized pattern of this mold was not degraded by
      soaking at 350 degrees C for 10 min and the pattern fidelity was maintained after
      10 separate cyclic heating tests between 0 degrees C and 350 degrees C. The
      substrate of this flexible mold was PI film, and a UV-cured polyurethane acrylate
      (PUA) layer was used to form the nano-scale patterns. The durability of this
      polymeric mold was tested by repetitive hot embossing processes. Nano-scale
      patterns of the mold were readily transferred to a PMMA layer coated onto a Si
      substrate by hot embossing lithography at 180 degrees C. After 10 cycles of hot
      embossing processes, no damage or degradation was observed in the flexible
      polymer mold. Using this polymer mold, patterns as small as 50 nm were
      successfully transferred to a Si substrate. Due to the flexibility of the polymer
      mold, nano-scale patterns were successfully transferred to a non-flat acryl
      substrate by hot embossing lithography.

PMID- 22849137
TI  - Current stress induced electrical instability in transparent zinc tin oxide thin
      film transistors.
AB  - Transparent zinc tin oxide thin-film transistors (ZTO-TFTs) [Zn:Sn = 4:1-2:1]
      have been fabricated so as to estimate the electrical instability under constant
      current stress. The relative intensity of the drain current noise power spectra
      density has been shown to have a typical 1/f-noise character, and it is implied
      that the mobility fluctuation in ZTO-TFT [Zn:Sn = 4:1] can be enhanced by a short
      range ordering in amorphous Zn-Sn-oxide, causing a larger shift of the threshold
      voltage (deltaV(th)).

PMID- 22849138
TI  - Characteristics of a-IGZO/ITO hybrid layer deposited by magnetron sputtering.
AB  - Transparent a-IGZO (In-Ga-Zn-O) films have been actively studied for use in the
      fabrication of high-quality TFTs. In this study, a-IGZO films and a-IGZO/ITO
      double layers were deposited by DC magnetron sputtering under various oxygen flow
      rates. The a-IGZO films showed an amorphous structure up to 500 degrees C. The
      deposition rate of these films decreased with an increase in the amount of oxygen
      gas. The amount of indium atoms in the film was confirmed to be 11.4% higher than
      the target. The resistivity of double layer follows the rules for parallel DC
      circuits The maximum Hall mobility of the a-IGZO/ITO double layers was found to
      be 37.42 cm2/V x N s. The electrical properties of the double layers were
      strongly dependent on their thickness ratio. The IGZO/ITO double layer was
      subjected to compressive stress, while the ITO/IGZO double layer was subjected to
      tensile stress. The bending tolerance was found to depend on the a-IGZO
      thickness.

PMID- 22849139
TI  - Synthesis of Ga-doped ZnO nanorods using an aqueous solution method for a
      piezoelectric nanogenerator.
AB  - Mechanical energy is a potential energy source for self-powered electronic
      devices. Due to their unique semiconducting and piezoelectric properties,
      wurtzite-structured nanomaterials have been considered as potential candidates
      for piezoelectric nanogenerators that convert mechanical energy into electricity.
      In the present work, we report on the growth of Ga-doped ZnO (GZO) nanorods and
      investigate the performance of nanogenerators fabricated from undoped ZnO (UZO)
      nanorods, low Ga-doped ZnO (LGZO) nanorods, and high Ga-doped ZnO (HGZO)
      nanorods. A nanogenerator integrated with LGZO nanorods exhibited a current
      density of 1.2 microA/cm2, an enhancement over the 0.4 microA/cm2 and 0.7
      microA/cm2 current densities of nanogenerators integrated with UZO and HGZO
      nanorods, respectively.

PMID- 22849140
TI  - Study of sintering behavior of vapor forms of 1-octanethiol coated copper
      nanoparticles for application to ink-jet printing technology.
AB  - Sub-50 nm copper nanoparticles coated with sub-5 nm 1-octanethiol layer for
      oxidation inhibition were examined to confirm the 1-octanethiol removal
      temperature as the sub-50 nm copper nanoparticles are sintered. As a result, 1
      octanethiol Self-Assembled Multi-layers (SAMs) on sub-50 nm copper nanoparticles
      were successfully removed before sintering of copper nanoparticles so that a high
      density of copper line could be obtained. Finally, the line resistivity was
      measured and compared to verify the effect of sintering in different atmospheres.
      As a result, electrical resistivity of the copper pattern sintered in hydrogen
      atmosphere was measured at 6.96 x 10(-6) ohm-cm whereas that of the copper
      pattern sintered in mixed gas atmosphere was measured at 2.62 x 10(-5) ohm-cm.
      Thus, sintering of copper patterns was successfully done to show low electrical
      resistivity values. Moreover, removal of 1-octanethiol coating after sintering
      process was confirmed using X-ray photoelectron spectroscopy (XPS) analysis. By
      showing no sulfur content, XPS results indicate that 1-octanethiol is completely
      removed. Therefore, the vapor form of 1-octanethiol coating layers can be safely
      used as an oxidation inhibition layer for low temperature sintering processes and
      ink-jet applications.

PMID- 22849141
TI  - Enhanced luminescence of Cu-In-S nanocrystals by surface modification.
AB  - We have synthesized highly luminescent Cu-In-S nanocrystals by heating the
      mixture of metal carboxylates and alkylthiol under inert atmosphere. We modified
      the surface of CIS nanocrystals with zinc carboxylate and subsequent injection of
      alkylthiol. As a result of the surface modification, highly luminescent CIS@ZnS
      core/shell nanocrystals were synthesized. The luminescence quantum yield (QY) of
      best CIS@ZnS nanocrystals was above 50%, which is more than 10 times higher than
      the initial QY of CIS nanocrystals before surface modification (QY = 3%).
      Detailed study on the luminescence mechanism implies that etching of the surface
      of nanocrystals by dissociated carboxylate group (CH3COO-) and formation of
      epitaxial shell by Zn with sulfur from alkylthiol efficiently removed the surface
      defects which are major non-radiative recombination sites in semiconductor
      nanocrystals. In this study, we developed a novel surface modification route for
      monodispersed highly luminescent Cu-In-S nanocrystals with less toxic and highly
      stable precursors.

PMID- 22849142
TI  - Structural chemistry of M2Si5N8:Eu2+ (M = Ca, Sr, Ba) phosphor via structural
      refinement.
AB  - Structural refinement using X-ray powder diffraction data and geometry energy
      calculations using quantum mechanics were used to investigate the preferential
      substitution sites and the amount of Eu2+ ions in the host lattice of alkaline
      earth elements co-doped M2Si5N8:Eu2+ (M = Ca, Sr, and Ba), which is a red color
      emitting nitride phosphor prepared via a carbothermal reaction method. Of the
      possible preferential sites, the preferential site proposed by the structural
      refinement results, in which the Eu2+ ions might preferentially occupy nine
      coordinated sites with nitrogen in M2Si5N8:Eu2+, was confirmed via geometry
      energy calculations using a first-principle based on the density-functional
      theory. The final converged weighted R factor (R(wp)) and the goodness-of-fit
      indicator [S(= R(wp)/R(e))] were 9.51% and 1.77, respectively. Each occupancy of
      Eu2+ ions for the two non-equivalent M sites, M(1) and M(2), was 0.10(2) and
      0.04(2), respectively. The final refined model described the crystal structure in
      a space group Pmn2, (No. 31) with Z = 2, a = 5.7424(1) angstroms, b = 6.8837(1)
      angstroms, c = 9.3586(1) angstroms, and alpha(= beta= gamma)= 90 degrees.

PMID- 22849143
TI  - Light extraction from organic light emitting diodes using chemically etched glass
      substrates.
AB  - We have manufactured highly efficient OLED devices fabricated on chemically
      etched glass substrates. The external quantum efficiency of the OLED devices with
      the etched glass substrates was increased by 5-27% in comparison with the
      reference flat glass substrate. Surface morphology, such as indented patterns,
      significantly affected the external luminance efficiency. A clean surface and the
      presence of smooth bent edges of indented patterns were found to be important for
      improving the external luminous efficacy.

PMID- 22849144
TI  - Efficient deep-blue organic light-emitting diodes using double-emitting layer.
AB  - Efficient deep-blue organic light-emitting diodes were demonstrated using 1,4
      tetranaphthalene doped in double-emitting layers (D-EMLs) consisting of 2-methyl
      9,10-di(2-naphthyl)anthracene and 4'-(dinaphthalen-2-yl)-1,1'-binaphthyl as blue
      hosts. The device with D-EML exhibits good confinement of holes and electrons, as
      well as a broad recombination zone. The optimized device showed a peak current
      efficiency of 3.67 cd/A, a peak external quantum efficiency of 3.97%, and
      Commission Internationale de L'Eclairage coordinates of (0.16, 0.10).

PMID- 22849145
TI  - Highly efficient red phosphorescent organic light-emitting devices using
      iridium(III) complexes based on 2-(biphenyl-3-yl)quinoline derived ligands.
AB  - Red phosphorescent emitters were synthesized based on Ir(III) phenylquinoline
      complexes for applications to OLEDs. Ir(III) complexes 1-3 were based on 2
      (biphenyl-3-yl)-quinoline units connected to various phenyl groups such as 5
      phenyl, 5-(4-fluorophenyl), and 6-phenyl groups. The EL efficiencies were quite
      sensitive to the structural features of the dopants in the emitting layers. In
      particular, a high-efficiency red OLED was fabricated using complex 1 as the
      dopant in the emitting layer. This OLED showed a maximum luminance, luminous
      efficiency, power efficiency, external quantum efficiency and CIE(x,y)
      coordinates of 21,600 cd/m2 at 16 V, 11.80 cd/A at 20 mA/cm2, 3.57 Im/W at 20
      mA/cm2, 10.90% at 20 mA/cm2, and (x = 0.63, y = 0.32) at 12 V, respectively.

PMID- 22849146
TI  - Investigation of hole transport layer in relation to the properties of organic
      solar cells.
AB  - Organic solar cells based on a blend of copper phthalocyanine and bulk fullerene
      are fabricated with a double hole transport layer system. The double hole
      transport layer was composed of poly3,4
      ethylenedioxythiophene:polystyrenesulfonate, and copper phthalocyanine and
      inserted between the anode and active layer. The double hole transport layer
      system utilizes advantages of both layer. The poly3,4
      ethylenedioxythiophene:polystyrenesulfonate layer modifies the surface morphology
      of the ITO anode and the copper phthalocyanine layer enhances hole transport. In
      order to enhance the conductivity of the modification layer, the optimal amount
      of glycerol is doped into poly3,4-ethylenedioxythiophene:polystyrenesulfonate.
      Furthermore, the photovoltaic characteristics are further improved. Insertion of
      the double hole transport layer with a 4 nm-thick copper phthalocyanine layer
      resulted in open circuit voltage, short current, and power conversion efficiency
      as high as 0.46 V, 8.8 mA/cm2 and 1.37%, respectively.

PMID- 22849147
TI  - Nano-scale texturing of borosilicate glasses using CF4-based plasma discharge for
      application in thin film solar cells.
AB  - Random plasma treatment techniques were used as a texturing method to reduce the
      surface reflection of glass substrates in thin film solar cells. Various gas
      mixtures were used for the plasma discharge in an effort to examine the texturing
      mechanism. Using a plasma treatment comprising CF4/O2 and CF4/Ar with a gas flow
      ratio of 1 to 2, the surface reflectance could be decreased to 6.83% and 6.82%,
      respectively. The surface treatment was very effective with the use of a low RF
      power of 50 W and an optimal time of 5 min. It is considered that the optical
      characteristics of the glass substrate are highly correlated to its surface
      morphology which can be produced not only through nano-scale chemical reactions
      with radicals but also through ion flux bombardment.

PMID- 22849148
TI  - Photovoltaic performance of dye-sensitized solar cell low temperature growth of
      ZnO nanorods using chemical bath deposition.
AB  - Nanostructured ZnO photoelectrodes were synthesized on fluorine-doped tin oxide
      (FTO) glass substrates that were spin-coated with a sol-gel based ZnO seed layer
      via a chemical bath deposition (CBD) method at varying times of 1, 2, 4, and 8 h.
      Then, TiO2 nanoparticulate electrodes were prepared on ZnO nanorods using the
      doctor blade technique. The uniformly grown ZnO nanorod layer had a length of
      approximately 710 nm on the FTO glass substrate with wurtzite structures which
      was confirmed through X-ray diffraction patterns. The length and diameter of the
      ZnO nanorods increased with an increase in the deposition time. The DSSCs
      fabricated with TiO2 nanoparticulate/grown ZnO nanorods and grown for 8 h showed
      the maximum efficiency (5.51%) with a short circuit current density (J(sc)) of
      12.21 mA/cm2 and an open circuit voltage (V(oc)) of 0.70 at 100 mW/cm2 light
      intensity.

PMID- 22849149
TI  - Behavior of the impurity-rich phase in metallurgical grade silicon during
      fractional melting.
AB  - A new fractional melting (FM) process that uses centrifugal force to separate the
      liquid from the cake (liquid + solid) was developed for refining metallurgical
      grade Si. The behavior of the solute and the refining mechanism during the FM
      process were studied using scanning electron microscopy (SEM) and electron probe
      microanalysis (EPMA). During the FM, the solutes migrated very quickly and
      aggregated at seemingly disordered locations, where they subsequently melted
      before the silicon bulk matrix melted.

PMID- 22849150
TI  - Fabrication of dye-sensitized solar cell (DSSC) using different particle sizes of
      TiO2 deposited via nano-particle deposition system (NPDS).
AB  - TiO2 layers were fabricated using a nano-particle deposition system (NPDS) on
      transparent conductive oxide (TCO) glass for dye sensitized solar cells (DSSCs).
      Conventionally, TiO2 paste for working electrodes has been fabricated using paste
      type methods. The fabricated paste composed of a mixture of nano-sized TiO2
      powders, binders and solutions is then painted on TCO glass. After drying, the
      TiO2 layer on TCO glass is sintered to make a path for electron transfer. TiO2
      layers formed by this paste type method require numerous steps, which can be time
      consuming. In this study, TiO2 powders were sprayed directly on TCO glass using
      NPDS in order to simplify the fabrication steps. To improve porosity and produce
      scattering layers, commercial nanocrystalline TiO, powders with different sizes
      were alternately deposited. Moreover, powders with different sizes were mixed and
      deposited on the TCO glass. The results indicate that the DSSCs with a TiO2 layer
      composed of different particle sizes had better cell performance than the cells
      assembled with single-sized TiO2 particles. Therefore, this study shows that a
      dry TiO2 coating process is possible for DSSC fabrication to improve its cell
      efficiencies, and this method can easily be applied on flexible substrates since
      NPDS is a room-temperature deposition process.

PMID- 22849151
TI  - Improved photovoltaic properties of fluorene-thiophene-based copolymers by an
      electron-transporting triazole unit in the main chain.
AB  - An electron-transporting triazole (Tz) unit was introduced into the fluorene
      thiophene-based copolymer backbone via a Suzuki coupling reaction. The resulting
      copolymer, poly[9,9'-dioctyl-fluorene-co-5, 5-(4', 7'-di-2-thienyl-2', 1',3'
      benzothiadiazole)-co-(4-(4-butyl-phenyl)-3, 5-diphenyl-4H-1,2,4]triazole)]
      (PF3TBTz), was soluble in common organic solvents and can be easily used as the
      active layer in organic photovoltaic cells (OPVs). By the introduction of the
      triazole unit, the OPV performance was nearly doubled from 0.62% (PF3TB) to 1.25%
      (PF3TBTz) under the same conditions. The higher performance can be explained by
      the improved surface morphology, resulting in better charge photogeneration and
      higher short circuit current (J(sc)) value in PF3TBTz in comparison with PF3TB.
      The possibility of the use of triazole units in OPV applications are described
      herein.

PMID- 22849152
TI  - Investigation of crystallization behavior of CIG-Se bi-layer thin films.
AB  - Copper indium gallium diselenide (CIGSe) thin film was fabricated via a thermal
      treatment of GIG-Se bi-layer thin films. A CIG layer was prepared first, by a
      chemical solution deposition (CSD) process. The Se layer was deposited separately
      on the CIG layer by evaporation. The GIG-Se bi-layer then underwent a thermal
      treatment to cause a reaction between the two layers. In order to investigate the
      mechanism of CIG-Se bi-layer crystallization, the thermal treatment temperature
      was varied. The properties of the prepared CIGSe2 thin films were analyzed using
      X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive
      spectrometry (EDS), and UV-visible spectrophotometry.

PMID- 22849153
TI  - Thermoelectric properties of Bi2Te3-PbTe pseudo binary near the eutectic
      composition.
AB  - (Bi2Te3)(1-x)(PbTe)(x) binary systems near eutectic composition were prepared by
      melting of elemental metals and a sequential water quenching process and their
      microstructures and thermoelectric properties were investigated. Multiple phases
      such as Bi2Te3, BiPbTe and PbTe were observed due to phase separation when the
      composition x was higher than the eutectic point. Also the electrical conduction
      type of the alloys converted from p-type to n-type in the phase separated alloys.
      The lattice thermal conductivities in the phase-separated alloys are lower than
      those in alloys without phase separation, attributable to increased boundary
      scattering.

PMID- 22849154
TI  - Highly ordered large-area colloid templates for nanostructured TiO2 thin film gas
      sensors.
AB  - We report a novel process that uses highly ordered colloidal templating to
      fabricate nanostructured TiO2 thin film gas sensors. An O2 plasma treatment is
      used to decrease the contact angle of a water droplet on a SiO2/Si substrate from
      46 degrees to 3 degrees. The formation of this hydrophilic surface enhances the
      adhesion of polystyrene microspheres to the substrate during the spin coating of
      the colloidal solution, leading to a large-area colloid template of closely
      packed monolayer microspheres on the substrates. Embossed TiO2 thin film gas
      sensors fabricated through highly ordered colloidal templating using O2 plasma
      exhibit substantially enhanced gas sensing performance as compared to those
      without surface treatments prior to colloidal templating.

PMID- 22849155
TI  - Helix-coiled gold nanowires for molecular sensing.
AB  - Helix-coiled gold nanowires were fabricated by a templating route using unique
      composite templates consisting of anodic aluminum oxide (AAO) nanotubular
      membrane and confined mesoporous silica therein. A different degree of
      confinement energy induces a different degree of helix curvature of confined
      porous silica nanochannels in an AAO, which works as a hard template for the
      electrochemical deposition of gold, thereby rationally enabling a different
      degree of helix curvature of gold nano-replicas. From surface-enhanced Raman
      scattering experiments, we first found that helix-coiled gold nanowires show more
      distinctly enhanced molecule sensing efficiency than those from simple smooth
      gold nanowires, and gold nanowires with the narrower lateral width show more
      enhanced molecule sensing efficiency than those of thicker width helix nanowires.

PMID- 22849156
TI  - Effect of gold immersion time on the electrochemical migration property of
      electroless nickel/immersion gold surface finishing.
AB  - In this study, the electrochemical performance of an electroless nickel/immersion
      gold (ENIG) surface finish was evaluated as a function of the Au immersion time
      by the water immersion migration test. As the Au plating time increased, the
      electroless nickel phosphorous (EN-P) changed from amorphous to crystalline and
      then increased in crystallinity. X-ray diffraction (XRD) was used to evaluate the
      crystallinity of the plating layer. The electrical resistance of the electrodes
      was tracked as the sample was immersed in water with a 5 V bias. The
      microstructures of the electrodes after the electrochemical migration test were
      observed by using secondary electron microscopy (SEM) and energy dispersive
      spectroscopy (EDS). As the Au immersion time increased, the EN-P's crystallinity
      and Au thickness increased. This enhanced the electrochemical migration
      protection of the surface finish layer.

PMID- 22849157
TI  - Novel method to evaluate moisture permeation of the metal barrier coating on
      polymer substrate.
AB  - Water is detrimental to the performance of organic light-emitting devices and
      organic solar cells. A novel weight gain test (WGT) was introduced and
      demonstrated to measure the low permeation of water vapor through a metallic
      barrier coating on a polymer substrate. By using the WGT, the values of
      solubility, diffusivity and permeability for a sample are obtained with a simple
      experimental setup and diffusion equation. The WGT method has potential for the
      measurement of water-vapor permeation properties for samples with good barrier
      properties and irregular shape.

PMID- 22849158
TI  - Analysis of the electron transport properties in dye-sensitized solar cells using
      highly ordered TiO2 nanotubes and TiO2 nanoparticles.
AB  - This study uses TiO2 nanoparticles and highly ordered anatase TiO2 nanotubes
      (AOTnt) as thin film photoanodes for dye-sensitized solar cells (DSSCs). DSSCs
      are assembled by single-layer and double-layer films of photoanodes and their
      electron transfer performance is compared. TiO2 nanoparticles were fabricated by
      the sol-gel method, and AOTnts were grown on titanium foil. This study uses TiO2
      nanoparticles or AOTnts to prepare single-layer photoanodes and TiO2
      nanoparticles coated on an AOTnt film to fabricate double-layer photoanodes.
      These three different photoanodes are soaked in dye and assembled into DSSCs, and
      their open-loop voltage recession, electrochemical impedance, lifetime, life
      cycle, and effective diffusion coefficient are measured. Electron transfer
      efficiency of the photoanodes and light harvesting efficiency are further
      analyzed. The results show that the electron transfer efficiency, open-loop
      voltage recession, lifetime, life cycle, and effective diffusion coefficient of
      the DSSCs assembled using double-layer photoanodes (AOTnt-TiO2) are superior to
      those of single-layer photoanodes (TiO2 or AOTnt).

PMID- 22849159
TI  - Effects of a PbTiO3 insertion layer on the morphological and electromechanical
      characteristics of sol-gel-driven 0.2PZN-0.8PZT piezoelectric films for energy
      harvesters.
AB  - This study investigated the morphological and electromechanical characteristics
      of 0.2PZN-0.8PZT films fabricated using a PbTiO3 layer. Crack-free 1-microm-thick
      films with a pure perovskite phase were obtained on Pt/Ti/SiO2/Si substrates
      using a modified sol-gel deposition method. A highly dense and smooth morphology
      and a high piezoelectric coefficient (d33) of 230 pC/N were observed in a 0.2PZN
      0.8PZT film with a PbTiO3 insertion layer after annealing at 750 degrees C. The
      as-produced sol-gel-driven 0.2PZN-0.8PZT thin films are attractive for
      application to piezoelectrically operated microelectronic actuators, sensors, or
      energy harvesters due to their low facility cost, smooth surface, and excellent
      electromechanical characteristics.

PMID- 22849160
TI  - Electrochemical properties of solid polymer electrolytes prepared by the
      hard/soft acid base principle.
AB  - In order to improve the electrochemical properties including ionic conductivity
      of SPEs (solid polymer electrolytes), understanding of the interaction between
      the polymer and salt in the SPE is important. In this study, four types of
      polymer matrices and four types of salts were used according to the hard/soft
      acid base (HSAB) principle. The results of impedance measurement reveal that the
      ionic conductivities are affected by the HSAB principle at low salt
      concentration. With increasing salt content, however, the SPEs are influenced by
      the ion hopping property of salt rather than by the solubility of the polymer
      with salt. In contrast, the PPS-based SPE shows different characteristics because
      it is prepared as a slurry phase at high salt content.

PMID- 22849161
TI  - Electrochemical performance of poly(vinyl alcohol)-based solid polymer
      electrolyte for lithium polymer batteries.
AB  - Solid polymer electrolytes (SPEs) are an excellent alternative to liquid
      electrolytes due to their non-volatility, low toxicity, and high energy density.
      In this study, a SPE having the ion transport mechanism decoupled from segmental
      motion of a polymer based on poly(vinyl alcohol) (PVA) containing the salt
      lithium trifluoromethane sulfonate (LiCF3SO3, LiTf) has been prepared to overcome
      the low ionic conductivity of traditional SPEs at room temperature. PVA has a
      high glass transition temperature (358 K) and good mechanical properties, and
      despite being atactic, it can crystallize, especially if highly hydrolyzed. From
      an ac impedance analysis, it was found that the ionic conductivity of the PVA
      based SPE increased with increasing salt concentration. In particular, a dramatic
      increase was observed between 40 and 50 wt% of salt. The ionic conduction
      mechanism of the PVA-based SPE is proposed based on intensive study using FT-IR
      spectroscopic measurements, XRD and AFM. Through measurements of linear sweep
      voltammetry (LSV) and cyclic voltammetry (CV), it is also found that the SPE with
      PVA and LiCF3SO3 has good electrochemical stability.

PMID- 22849162
TI  - Synthesis and electrochemical properties of polyaniline nanofibers by interfacial
      polymerization.
AB  - Polyaniline nanofibers were prepared by interfacial polymerization with different
      organic solvents such as chloroform and carbon tetrachloride. Field emission
      scanning electron microscopy and transmission electron microscopy were used to
      study the morphological properties of polyaniline nanofibers. Chemical
      characterization was carried out using Fourier transform infrared spectroscopy,
      UV-Vis spectroscopy, and X-ray diffraction spectroscopy and surface area was
      measured using BET isotherm. Polyaniline nanofibers doped with lithium
      hexafluorophosphate were prepared and their electrochemical properties were
      evaluated.

PMID- 22849163
TI  - Nanocrystalline indium tin oxide fabricated via sol-gel combustion for
      electrochemical luminescence cells.
AB  - Nanoporous indium tin oxide (ITO) was synthesized via a sol-gel combustion hybrid
      method using Ketjenblack as a fuel. The effects of the sol-gel combustion
      conditions on the structures and morphology of the ITO particles were studied.
      The size of the nanoporous powder was found to be 20-30 nm in diameter. The layer
      of the nanoporous ITO electrode (-10 microm thickness) with large surface area (
      360 m2/g) was fabricated for an electrochemical luminescence (ECL) cell. At 4 V
      bias, the ECL efficiency of the cell consisting of the nanoporous ITO layer was
      approximately 1050 cd/m2, which is significantly higher than the cell using only
      the FTO electrode (450 cd/m2). The nanoporous ITO layer was effective in
      increasing the ECL intensities.

PMID- 22849164
TI  - Interface modification of cathode electrode using dimmethyldicyanoquinonediimine
      as a charge transfer layer in organic photovoltaic cell.
AB  - Various metals for the cathode electrode of organic electronic devices have been
      used in order to improve carrier injection and contact resistance etc. However,
      metal electrodes have some disadvantages such as rough surfaces, inadequate
      interfacial durability and unsuitable work functions. In the present work, we
      have fabricated an organic photovoltaic cell consisting of
      ITO/PEDOT:PSS/P3HT:PCBM/DMDCNQI/Al. The dimmethyldicyanoquinonediimine (DMDCNQI)
      compound was used as an organic n-type charge transfer complex between the
      cathode electrode and an organic active layer to improve contact resistance and
      electron transport ability. The prepared device shows a high short-circuit
      current density of 10.39 mA/cm2 and a maximum power conversion efficiency of
      3.10%.

PMID- 22849165
TI  - Fullerene C60 coated silicon nanowires as anode materials for lithium secondary
      batteries.
AB  - A Fullerene C60 film was introduced as a coating layer for silicon nanowires (Si
      NWs) by a plasma assisted thermal evaporation technique. The morphology and
      structural characteristics of the materials were studied by scanning electron
      microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). SEM observations
      showed that the shape of the nanowire structure was maintained after the C60
      coating and the XPS analysis confirmed the presence of the carbon coating layer.
      The electrochemical characteristics of C60 coated Si NWs as anode materials were
      examined by charge-discharge tests and electrochemical impedance measurements.
      With the C60 film coating, Si NW electrodes exhibited a higher initial coulombic
      efficiency of 77% and a higher specific capacity of 2020 mA h g(-1) after the
      30th cycle at a current density of 100 microA cm(-2) with cut-off voltage between
      0-1.5 V. These improved electrochemical characteristics are attributed to the
      presence of the C60 coating layer which suppresses side reaction with the
      electrolyte and maintains the structural integrity of the Si NW electrodes during
      cycle tests.

PMID- 22849166
TI  - Top-down processed silicon nanowires for thermoelectric applications.
AB  - 50 nm wide n-type silicon nanowires have been manufactured by using a top-down
      process in order to investigate the thermoelectric properties of silicon
      nanowire. Nanowire test structures with platinum heaters and temperature sensors
      were fabricated. The extracted temperature coefficient of resistance (TCR) of the
      temperature sensors was 786.6 PPM/K. Also, the extracted Seebeck coefficient and
      power factor of the 50 nm wide phosphorus doped n-type silicon nanowires were 
      118 miroV/K and 2.16 mW x K(-2) x m(-1).

PMID- 22849167
TI  - Synthesis of lead-free (K, Na)(Nb, Ta)O3 nanopowders using a sol-gel process.
AB  - Lead-free (K0.5Na0.5)(Nb0.7Ta0.3)O3 piezoelectric material was successfully
      synthesized via a sol-gel process. Crystalline (K0.5Na0.5)(Nb0.7Ta0.3)O3
      nanopowders were obtained after heat treatment at 700 degrees C. The particle
      size was estimated to be 87nm +/- 23 nm. The transmission electron microscopy
      images showed that individual nanoparticles were single crystalline and had a
      pseudo-cubic structure with a lattice parameter of -3.96 angstroms. Both X-ray
      diffraction and scanning electron microscopy studies consistently showed that the
      crystallization of the (K0.5Na0.5)(Nb0.7Ta0.3)O3 occurred slightly above 500
      degrees C. The samples have an appropriate stoichiometry as found via energy
      dispersive X-ray spectroscopy. The demonstration of the synthesis of
      (K0.5Na0.5)(Nb0.7Ta0.3)O3 via a sol-gel process as presented in this paper can
      provide an important foundation for the development of a synthetic route towards
      (K0.5Na0.5)(Nb0.7Ta0.3)O3 doped with various other elements for high performance
      piezoelectric devices.

PMID- 22849168
TI  - Characterizations of Ga-doped ZnO nanowires depending on growth temperature and
      target-substrate distance in hot-walled pulsed laser deposition.
AB  - Using a hot-walled pulsed laser deposition (HW-PLD), nanowires (NWs) comprising 3
      weight% Ga-doped ZnO (3GZO) have been successfully grown on a sapphire substrate.
      The structural and optical properties of 3GZO nanostructures have also been
      systematically investigated with respect to the target-substrate (T-S) distance
      and the growth temperature. The morphology transformations of nanostructures such
      as nano-horns, NWs, and clusters are strongly affected by growth temperatures due
      to different thermal energy. Also, the morphologies of nanostructures--including
      length, diameter, and density--are strongly affected by the T-S distance,
      illustrating a close correlation between the growth kinetics and the position in
      the plume formed by the particles from the GZO target. Also, the exciton that is
      bound to the neutral donor (D(0)X) peak of the 3GZO nanostructures is found at
      the low temperature PL spectra, indicating successful Ga-doping into ZnO NWs.

PMID- 22849169
TI  - Synthesis of Co3O4 nanowire arrays supported on Ni foam for removal of volatile
      organic compounds.
AB  - Crystalline Co3O4 nanowire arrays freely supported on Ni foam are successfully
      synthesized using a template-free method. The effects of reaction time,
      concentration of reactants, and temperature on the morphology of the nanowires
      are studied. The results indicate that uniform Co3O4 nanowires could be
      synthesized at 90 degrees C, and a transformation of the samples' morphology from
      nanoparticles to nanowires to microrods is observed by controlling the
      concentration of the reactants. The well-ordered nanowires synthesized under the
      selected reaction conditions are composed of spinel Co3O4 with diameters of 500
      580 nm and lengths of 6-8 microm. These nanowires show good catalytic activity
      for the ozone catalytic oxidation of toluene.

PMID- 22849170
TI  - Fabrication of p-type silicon nanowire arrays with a high aspect ratio using
      electrochemical and alkaline etching.
AB  - We report on the fabrication of silicon nanostructures with a high aspect ratio
      that were created using a combination of electrochemical etching and alkaline
      etching. With this technique, we were able to fabricate nano- and/or micro-wire
      structures that are perfectly periodic over large areas of 3.14 cm2. After porous
      silicon was created by electrochemical etching, the effect of post-alkaline
      etching was investigated to determine how changes in the etching time, solution
      concentration and temperature of the etchant influenced the silicon morphology.
      As a result, periodic silicon wire arrays with good vertical alignment were
      obtained, and these arrays had a width of less than 500 nm and/or a high aspect
      ratio of more than 20.

PMID- 22849171
TI  - Enhanced thermal properties of graphene oxide-incorporated polymeric
      microspheres.
AB  - Polystyrene (PS) microspheres coated with graphene oxide (GO) were prepared and
      the variation of their thermal properties according to the GO loading was
      examined. The GO content in the PS-GO nanocomposites was controlled by the GO
      dispersions at various concentrations. The GO was coated onto the surface of the
      PS microspheres through the strong ionic interaction between polyvinylpyrrolidone
      and the GO sheet. The thermal properties of the GO incorporated PS microspheres
      were affected by the GO, which disturbed the chain activity and exhibited
      effective heat shielding. It also delayed the permeation of oxygen and hindered
      the escape of volatile degradation products from the PS-GO nanocomposites. In
      addition, the thermal degradation temperature of the nanocomposites was increased
      above 15 degrees C and their T(g) was also increased above 4.0 degrees C. PS-GO
      exhibited higher thermal conductivity (0.173 W/mK) than that of pure PS (0.117
      W/mK).

PMID- 22849172
TI  - Improvement of wafer-level Cu-to-Cu bonding quality using wet chemical
      pretreatment.
AB  - We have evaluated the effect of wet chemical treatment on the interfacial bonding
      strength of Cu-to-Cu direct bonding. The oxide on a Cu-deposited wafer can be
      removed by a solution made of hydrofluoric acid and sulfuric acid (HF/H2SO4) or
      diluted hydrochloric acid (HCl/H2O), which can also improve the bonding quality
      of Cu-to-Cu bonds. Two 4-inch Cu-deposited wafers were bonded at 250 degrees C
      via the thermo-compression method. The interfacial adhesion energy of Cu-to-Cu
      bonding was quantitatively measured by the four-point bending method. After
      chemical pretreatment for 30 seconds with HF/H2SO4 and HCl:H2O solutions, the
      measured interfacial adhesion energies were 4.91 J/m2 and 5.51 J/m2,
      respectively. Microstructural examination of the Cu bonding interfaces showed
      that the interfacial bonding quality of Cu-to-Cu bonds improved under proper wet
      chemical etching conditions. Wafer-level cleaning by wet chemical treatment of
      the Cu surface was found to be a very effective way to improve the bonding
      quality of Cu bonds, even at bonding temperatures lower than 300 degrees C.

PMID- 22849173
TI  - Electroplating characteristics of eutectic Sn-Cu ions for micro-solder bump on a
      Si chip.
AB  - The fabrication of fine bumps on a Si chip is an important issue due to the trend
      of smaller sized and multi-functioning electronics. In this study, a Sn-Cu near
      eutectic solder bump was fabricated by electroplating. A Si wafer was used as a
      substrate, while layers of the Under Bump Metallization (UBM) of Al/Cu/Ni/Au
      (400/300/400/20 nm in each) were coated onto the Si wafer by electron beam
      evaporation. The bumps on the UBM were plated by a direct current, and the bump
      size was 20 x 20 x 10 microm with a 50 microm pitch. Characteristics of the
      electroplated bumps were examined by XRD, EDS and EPMA. A polarization curve was
      established to find a potential range of electrodeposition of Sn-Cu. By plating
      with a reduction current density of 1 A/dm2 for 23 min, a near eutectic Sn-Cu
      bump was obtained. The bump height increased in current density, namely from 2.25
      microm at 0.5 A/dm2 to 6.58 microm at 2 A/dm2 from 10 min of plating. In the
      electroplated state, a beta-Sn and Sn-Cu intermetallic compound (IMC) coexisted
      in the bumps. Cu3Sn and Ni3Sn4 IMCs were discovered by XRD analysis along the
      interface between the bump and the UBM.

PMID- 22849174
TI  - Atomic layer deposition of SiO2 thin films using tetrakis(ethylamino)silane and
      ozone.
AB  - We examined the atomic layer deposition (ALD) of silicon dioxide thin films on a
      silicon wafer by alternating exposures to tetrakis(ethylamino)silane
      [Si(NHC2H5)4] and O3. The growth kinetics of silicon oxide films was examined at
      substrate temperatures ranging from 325 to 514 degrees C. The deposition was
      governed by a self-limiting surface reaction, and the growth rate at 478 degrees
      C was saturated at 0.17 nm/cycle for Si(NHC2H5)4 exposures of 2 x 10(6) L (1 L =
      10(-6) Torr x s). The films deposited at 365-404 degrees C exhibited a higher
      deposition rate of 0.20-0.21 nm/cycle. However, they contained impurities, such
      as carbon and nitrogen, and showed poor film qualities. The concentration of
      impurities decreased with increasing substrate temperature. It was found that the
      films deposited in the high-temperature regime (478-514 degrees C) showed
      excellent physical and electrical properties equivalent to those of LPCVD films.

PMID- 22849175
TI  - In-situ electrical conductivity measurement of oxidation of tin nanocluster film.
AB  - An in-situ electrical conductivity measurement of thin films of tin oxide
      nanoclusters for nano-devices was performed during metal cluster deposition and
      subsequent oxidation. From the current observation, the percolation threshold and
      the oxidation process are suggested. During baking at 200 degrees C, tin
      nanoclusters were transformed into low-conductivity stannous oxide and then into
      high-conductivity stannic oxide. From electron micrographs, it is suggested that
      the baking procedure is responsible for changing the oxide state and/or the
      crystallinity of the individual nanoclusters rather than changing the morphology
      of the film.

PMID- 22849176
TI  - Synthesis, characterization, and electrical properties of regioregular alkyl
      substituted PEDOTt.
AB  - The regioregular hexyl-substituted poly(3,4-ethylenedioxy-2-thiophenylthiophene)
      (PEDOTt), structurally alternating copolymer of EDOT and thiophene, was
      synthesized via the Grignard Metathesis (GRIM) using catalytic amounts of
      Ni(dppp)Cl2. The products were characterized by 1H NMR spectroscopy, UV-vis
      spectroscopy and XRD. The alkyl-substituted conjugated polymer showed an
      enhancement of solubility in common organic solvents. Based on XRD data, the
      regioregular hexyl-substituted poly(3,4-ethylenedioxy-2-thiophenylthiophene)
      (PEDOTt) shows better crystallinity than the regiorandom hexyl-substituted PEDOTt
      owing to self-ordering. In addition, regioregular hexyl-PEDOTt has a conductivity
      of 0.788 S/cm by iodine doping.

PMID- 22849177
TI  - Effects of in-plane magnetization orientation on magnetic and electronic
      properties in a Bcc Co (001)/rock salt MgO (001)/Bcc Co (001) magnetic tunnel
      junction system: ab initio calculations.
AB  - Ab initio calculations were performed on a fully epitaxial bcc Co (001)/rock salt
      MgO (001)/bcc Co (001) magnetic tunnel junction system for two cases where the
      magnetization is parallel to bcc Co [100] and to bcc Co [110]. Structural
      optimization reveals that the two cases are equivalent systems and that the Co
      electrodes contract in the z-direction whereas the MgO insulating barrier
      expands. The magnetic moments of each monolayer vary slightly in each case;
      furthermore, only the magnetic moment at the surface of the Co atom shows any
      enhancement (12%). The layer decomposed density of states profiles reveals that
      the bonding character of the junction interface is derived mainly from the 2p-3d
      hybridization of the MgO and Co interfacial atoms.

PMID- 22849178
TI  - Fabrication and characterization of white polymer light emitting diodes using
      PFO:MDMO-PPV.
AB  - White polymer light emitting diodes (WPLEDs) with a glass/ITO/PEDOT:PSS/PFO:MDMO
      PPV/ TPBI/LIF/Al structure were fabricated in order to investigate the optimum
      doping concentration of the emission materials. PEDOT:PSS was introduced as the
      hole transport material. The PFO and MDMO-PPV were used as the light emitting
      host and the guest materials, respectively. The PFO:MDMO-PPV mixed solution was
      spin-coated onto the PEDOT:PSS/ITO substrate. TPBI, LiF and Al were deposited by
      thermal evaporation as the hole blocking, electron injection, and cathode
      materials, respectively. As a result, the current density and luminance of the
      WPLED with the 20.0 wt% MDMO-PPV concentration in the PFO host material were
      found to be about 365 mA/cm2 and 4315 cd/m2, respectively. The maximum external
      quantum efficiency (EQE) of the same sample was found to be 11.26%, which may be
      ascribed to the efficient energy transfer from the PFO host to the MDMO-PPV guest
      material.

PMID- 22849179
TI  - Flexible white organic light-emitting devices with a porous red polymer layer and
      a blue small molecular layer utilizing a phase separation of blended polymer.
AB  - Flexible white organic light-emitting devices (WOLEDs) with an emitting layer
      consisting of a porous red poly(2-methoxy-5-(2'-ethyl-hexyloxy)-1,4
      phenylenevinylene) (MEH-PPV) polymer layer and a blue 4,4'-bis(2,2'
      diphenylvinyl)-1,1'-biphenyl (DPVBi) small molecular layer were fabricated on
      polyethylene terephthalate substrates. The current density of the flexible WOLEDs
      fabricated with a blend layer formed with a higher spincoating speed was
      significantly higher than that of a device fabricated with a lower spincoating
      speed, due to the higher pore density. The ratio between the red and the blue
      color peak intensities of the electroluminescence spectra for the flexible WOLEDs
      with a porous red MEH-PPV polymer layer and a blue DPVBi small molecular layer
      was controlled by the spincoating speed of the blend layer.

PMID- 22849180
TI  - Electroreduction of H2O2 by Co3O4 and NiCo2O4 nanowires and beta-Ni(OH)2
      nanoplates grown on Ni foam.
AB  - Nanowires (Co3O4 and NiCo2O4) and nanoplates (beta-Ni(OH)2) grown on Ni foam are
      successfully prepared by a template-free method and used as cathode electrodes
      for the electroreduction of H2O2, in an alkaline medium. Catalytic performance is
      investigated via cyclic voltammetry and chronoamperometry. The Co3O4 and NiCo2O4
      nanowire electrodes exhibit much better catalytic activity, stability, and mass
      transfer properties for H2O2 electroreduction than pressed Co3O4 and NiCo2O4
      nanoparticle/carbon/PTFE electrodes. A current density of 101.8 mA cm(-2) and
      122.7 mA cm(-2) are respectively achieved on Co3O4 and NiCo2O4 nanowire
      electrodes at -0.4 V in 0.4 mol/L H2O2, and 3.0 mol/L NaOH solution at room
      temperature.

PMID- 22849181
TI  - Fire-through Ag contact formation for crystalline Si solar cells using single
      step inkjet printing.
AB  - Inkjet-printed Ag metallization is a promising method of forming front-side
      contacts on Si solar cells due to its non-contact printing nature and fine grid
      resolution. However, conventional Ag inks are unable to punch through the SiN(x)
      anti-reflection coating (ARC) layer on emitter Si surfaces. In this study, a
      novel formulation of Ag ink is examined for the formation of fire-through
      contacts on a SiN(x)-coated Si substrate using the single-step printing of Ag
      ink, followed by rapid thermal annealing at 800 degrees C. In order to formulate
      Ag inks with fire-through contact formation capabilities, a liquid etching agent
      was first formulated by dissolving metal nitrates in an organic solvent and then
      mixing the resulting solution with a commercial Ag nanoparticle ink at various
      volume ratios. During the firing process, the dissolved metal nitrates decomposed
      into metal oxides and acted in a similar manner to the glass frit contained in Ag
      pastes for screen-printed Ag metallization. The newly formulated ink with a 1 wt%
      loading ratio of metal oxides to Ag formed finely distributed Ag crystallites on
      the Si substrate after firing at 800 degrees C for 1 min.

PMID- 22849182
TI  - High-temperature thermoelectric properties of Na(Co0.91, Ni0.09)2O4 fabricated by
      solution combustion method for power generation.
AB  - High-quality nano-sized Na(Co0.91Ni0.09)2O4 powders, i.e., 27 nm in average size,
      were synthesized by the solution combustion route. The magnitude of the
      electrical conductivity, the Seebeck coefficient, and the power factor for
      Na(Co0.91Ni0.09)2O4 depended strongly on the fuel used and followed the order of
      aspartic acid > glutamic acid > alanine > glycine. The order of the
      thermoelectric characteristics was consistent with that of the density of
      Na(Co0.91Ni0.09)2O4. The maximal power factor (1.06 x 10(-3) Wm(-1) K(-2)) was
      achieved for aspartic acid-processed Na(Co0.91 Ni0.09)2O4 twice-sintered at 800
      degrees C. We believe that the solution combustion route was highly effective for
      fabricating high-efficiency thermoelectric materials.

PMID- 22849183
TI  - Growth and thermoelectric properties of multilayer thin film of bismuth telluride
      and indium selenide via rf magnetron sputtering.
AB  - A bismuth telluride (BT)/indium selenide (IS) multilayer film was deposited at
      room temperature by rf magnetron sputtering on a sapphire substrate in order to
      investigate how the multilayered structure affects the microstructure and
      thermoelectric properties. The effect of annealing at different temperatures was
      also studied. The results were compared with those from a BT film with the same
      thickness. A TEM study showed that the interface between the BT and IS layers
      became vague as the annealing temperature increased, and the BT layer
      crystallized while the IS layer did not. The presence of thin IS layers can help
      to limit the evaporation of Te from the BT/IS multilayer film, thus increasing
      the amount of Bi2Te3 phase in the multilayer film as compared with that of the BT
      film. An abrupt increase in the Seebeck coefficient of the multilayer film was
      observed when annealed at 300 degrees C, and the resistivity of the annealed
      multilayer film was high compared to that of the BT film. This result can also be
      explained by the proposed role of the IS layer, which limits the evaporation of
      Te at high temperature. The highest power factor of -3.9 x 10(-6) W/K2 cm was
      obtained at room temperature from the multilayer film annealed at 300 degrees C.

PMID- 22849184
TI  - Thermoelectric properties of Bi2Te3-In2Se3 composite thin films prepared by co
      sputtering.
AB  - Bi2Te3-In2Se3 films were prepared by co-sputtering followed by annealing, and
      their structural and thermoelectric properties were investigated. The immiscible
      nature of the two alloys results in precipitation of the second phase, thus
      leading to structures with self-assembled dots that are a few nanometers in
      scale. HAADF-STEM and HRTEM were used to confirm that In2Se3 nanodots that were a
      few nanometers in size did indeed form in the Bi2Te3 thin film. It was found that
      the incorporation of these nanodots can reduce the thermal conductivity of the
      thin film.

PMID- 22849185
TI  - Fabrication of copper nanoparticles in a thick polyimide film cured by rapid
      thermal annealing.
AB  - We investigated the imidization of a polyimide (PI) and the formation of Cu
      nanoparticles in a PI film by curinga precursor of PI (polyamic acid (PAA)
      dissolved in n-methyl-2-pyrrolidinone) in a reducing atmosphere in the rapid
      thermal annealing (RTA) system. A Cu film was deposited onto the SiO2/Si
      substrate, and the PAA was spin-coated onto the Cu film. After the PAA reacted
      with the Cu film, soft-baking was performed to evaporate the solvent. Finally,
      the PAA was imidized to PI at 450 degrees C by curing in a reducing atmosphere
      with the RTA. Fourier transform infrared spectroscopy showed that the PAA was
      successfully imidized by the RTA. X-ray diffraction patterns revealed that Cu
      nanoparticles formed by RTA curing at 450 degrees C for 5 minutes in a reducing
      atmosphere, and transmission electron microscopy showed that Cu nanoparticles
      about 6.5 nm in size were uniformly dispersed in the PI film. Curing by RTA is an
      attractive method because it takes only a few minutes.

PMID- 22849186
TI  - Electrochemical preparation of ionic liquid-stabilized palladium nanoparticles.
AB  - We have successfully synthesized ionic liquid (IL)-stabilized palladium (Pd)
      nanoparticles (NPs) by electrochemical reduction. The particle size was
      controlled by adjusting the current density. Transmission electron microscopic
      (TEM) images showed that the average diameters of the Pd NPs were 2.4, 3.2, and
      3.5 nm, depending on the synthetic conditions. Particle size increased as the
      current density and the length of the alkyl chain in the cation decreased. X-ray
      diffraction of the resulting NPs indicated that the particles had a crystalline
      structure. Overall, the results show that NPs can be finely tuned according to
      the kinds of ILs employed, as well as by electrochemical reduction.

PMID- 22849187
TI  - Crystallization of Au-Si/glass thin film: a real-time synchrotron X-ray
      scattering study.
AB  - The crystallization of amorphous, Si-rich, Au28Si72/glass thin film was studied
      in real-time synchrotron X-ray scattering experiments. The amorphous film
      crystallizes first into Au and Si phases at a low temperature of 206 degrees C.
      At annealing temperatures above eutectic temperature (T(E) = 360 degrees C), the
      Au phase melts while the Si phase rapidly grows further. The crystallized
      Au28Si72 thin film has nanowire-type grains with 1000-nm-length and 10-nm
      diameter. We confirm that the Au liquid phase contributes to the low-temperature
      crystallization of the Si solid phase for Si-nanowire growth.

PMID- 22849188
TI  - Ge oxidation in the remaining cores of Si(1-x)Ge(x) nanowires after prolonged
      oxidation.
AB  - For this investigation of the Ge behavior of condensed Si(1-y)Ge(y) (y > x) cores
      during the oxidation of Si(1-x)Ge(x) nanowires, Si(1-x)Ge(x) nanowires were grown
      in a tube furnace by the vapor-liquid-solid method and thermally oxidized. The
      test results were characterized using several techniques of transmission electron
      microscopy. The two types of Ge condensation are related to the diameter and Ge
      content of the nanowires. The consumption of Si atoms in prolonged oxidation
      caused the condensed SiGe cores to become Ge-only cores; and the continuous
      oxidation resulted in the oxidation of the Ge cores. The oxidation of Ge atoms
      was confirmed by scanning transmission electron microscopy.

PMID- 22849189
TI  - Tensile properties and thermal shock reliability of Sn-Ag-Cu solder joint with
      indium addition.
AB  - The thermal shock reliability and tensile properties of a newly developed
      quaternary Sn-1.2Ag-0.5Cu-0.4In (wt%) solder alloy were investigated and compared
      to those of ternary Sn-Ag-Cu based Pb-free solder alloys. It was revealed that
      the Sn-1.2Ag-0.5Cu-0.4In solder alloy shows better thermal shock reliability
      compared to the Sn-1.0Ag-0.5Cu and Sn-3.0Ag-0.5Cu solder alloys. The quaternary
      alloy has higher strength than Sn-1.0Ag-0.5Cu alloy, and higher elongation than
      Sn-3.0Ag-0.5Cu alloy. It was also revealed that the addition of indium promotes
      the formation of Ag3(Sn, In) phase in the solder joint during reflow process.

PMID- 22849190
TI  - A growth mechanism of porous film formed on Al in 0.6 M oxalic acid electrolyte.
AB  - Understanding of mechanism of porous film formation is of fundamental importance
      for anodizing in general because, the onset of pore initiation terminates the
      barrier film growth process over the macroscopic metal surface. Several
      mechanisms have been proposed to explain pore formation. They include direct
      injection of aluminum ions into electrolyte and a field-assisted dissolution
      mechanism. High-resolution scanning electron microscopy of anodized surfaces and
      direct TEM of ion beam thinned films and ultrarmicrotomed film sections have been
      employed to gain further insight into the mechanism of initial porous film growth
      in 0.6 M oxalic acid. From detailed examination of the behavior of the xenon
      tagged layer in the film during pore initiation and development in oxalic acid,
      the film structure of the barrier layer is found to be unstable during pore
      initiation and the instability of the film structure is possibly related to the
      field-assisted structure modification process.

PMID- 22849191
TI  - Effects of NH3 plasma pre-treatment of Ta substrate on atomic layer deposition of
      Cu thin film.
AB  - Cu has replaced Al as an interconnection material in ultra-large integrated
      circuits, reducing resistance capacitance delay and yielding higher electro
      migration reliability. However, as the feature size decreases, it becomes more
      difficult to produce reliable Cu wiring. In this work, the Plasma Enhanced Atomic
      Layer Deposition (PEALD) of Cu seed layers deposited on Ta substrates (both with
      and without NH3 plasma pretreatment) was investigated. The Cu seed layers
      deposited on NH3 plasma-pretreated Ta substrates were found to have favorable
      properties compared to films deposited without plasma pretreatment because of an
      increase in the surface energy and of the Ta substrate, which resulted in
      improved surface wetting.

PMID- 22849192
TI  - Properties of ZnO thin films co-doped with hydrogen and fluorine.
AB  - ZnO films co-doped with fluorine and hydrogen were prepared on Corning glass by
      radio frequency magnetron sputtering of ZnO targets with varying amounts of ZnF2
      in H2/Ar gas mixtures of varying H2 content. The ZnO films' electrical, optical,
      and structural properties in combination with their compositional properties were
      investigated. A small addition of H2 to the sputtering gas caused a drastic
      increase of Hall mobility with a marginal increase in carrier concentration,
      indicating an effective passivation of grain boundaries due to hydrogenation. For
      further increase of H2 in sputter gas, the Hall mobility remained at a relatively
      constant level while the carrier concentration increased steadily. Most of the
      ZnO films co-doped with fluorine and hydrogen showed average transmittance higher
      than 83% in the 400-800 nm range, while the average absorption coefficients were
      lower than 600 cm(-1), implying very low absorption loss in these films. It was
      discovered that the fabrication of ZnO films with a Hall mobility higher than 40
      cm2/Vs and a very low absorption loss in the visible range is possible by co
      doping hydrogen and fluorine.

PMID- 22849193
TI  - Effect of precursor ratio on the structural properties of ZnO thin films
      deposited by low pressure MOCVD.
AB  - The effect of precursor ratio (H2O/DEZ) on the texture orientation, surface
      morphology, optical transparency and electrical resistivity of ZnO thin films
      deposited by MOCVD was investigated. Deposition temperature and pressure were
      fixed at 120 degrees C and 0.67 torr, respectively. The precursor ratio was
      varied between 0.1 and 4. It was found that the texture orientation changed from
      (0002) to (1120) with increase of the precursor ratio. (1120) textured film shows
      well facetted tetrapod like rough surface morphology, which scatters the incident
      light very effectively. The electrical resistivity was in the range of about 0.1
      omega cm in the undoped state, which was found to decrease with increase of the
      film thickness and decrease of the precursor ratio.

PMID- 22849194
TI  - Electrical and optical properties of amorphous (In, Sn)-Ga-Zn-O thin film.
AB  - Films of amorphous In(1-x)Sn(x)GaZnO(delta) (a-ISGZO) (x = 0.0-1.0) were pulsed
      laser deposited at a temperature range of room temperature to 300 degrees C, and
      in order to systematically investigate the effect of replacing In with Sn on the
      properties of amorphous In-Ga-Zn-O (a-IGZO), the electrical and optical
      properties were measured. The amount of Sn in the deposited film, which was
      determined by X-ray photoelectron spectroscopy, was very close to the composition
      of the targets used. Hall mobility and carrier concentration decreased, and
      resistivity increased as the amount of Sn in the film increased. It was observed
      that the increase of Sn concentration in films was accompanied by the decrease of
      oxygen vacancy concentration, which led to the decrease of carrier concentration.
      The electrical mobility was decreased as the amount of Sn increased, which can be
      attributed to the increased number of subgap states, which was determined by the
      UV/VNIS spectrophotometer. Optical transparencies of all samples were larger than
      80% in the visible light range. Band gap values were also found to increase as
      the amount of Sn increased.

PMID- 22849195
TI  - Magnesium-doped zinc oxide electrochemically grown on fluorine-doped tin oxide
      substrate.
AB  - Nanostructures of magnesium (Mg) doped Zinc oxide (ZnO) were successfully
      deposited on conducting fluorine-doped tin oxide (FTO) coated glass plates by
      cathodic electrochemical deposition method at different potentials and
      temperature conditions. The deposited samples were characterized by XRD and SEM
      techniques to confirm their structures, morphologies and optical properties.
      These measurements show that Mg doped ZnO has a wurtzite structure and that the
      strongest intensity of the (002) peak is found at 60 degrees C and -1.0 V.
      Tunable transmittance of Mg doped ZnO has a band gap energy from 3.45 eV to 3.82
      eV, which is the direct evidence of doping.

PMID- 22849196
TI  - Electrical stress effect on the leakage current of metal-induced laterally
      crystallized p-channel poly-Si TFTs.
AB  - A p-type polycrystalline silicon thin-film transistor (TFT) was fabricated using
      the metal-induced lateral crystallization (MILC) technique at 550 degrees C. To
      reduce the leakage current in the MILC TFT, electrical stress (ES), newly
      developed in this work, was applied prior to the I(D)-V(G) measurements. It was
      found that ES is effective only when the TFT is under off-state. The stress gate
      voltage is related to the leakage current at high gate voltages and the electric
      field between the source and the drain to the leakage current at low gate
      voltages. The leakage current of the MILC TFT could be lowered to 10(-11) A for
      width/length ratios of 1/2 measured at the drain voltage of 3 V. A new plausible
      model has been suggested to explain the ES effect on the leakage current behavior
      in low-temperature polycrystalline silicon TFTs.

PMID- 22849197
TI  - Polymeric white organic light-emitting diodes with two emission layers.
AB  - A white light-emitting diode was fabricated by preparing multilayer emitting
      films with an inserted buffer layer. The device structures are
      ITO/PEDOT:PSS/Emissive layer/LiF/Al. The emissive layer comprises a yellow
      emitting layer of Poly[9,9-dioctylfluorenyl-2,7-diyl]-co-1,4-benzo-(2,1,3)
      thiadiazole (F8BT), a blue-emitting layer of Poly[9,9-di-(2'-ethylhexyl)fluorenyl
      2,7-diyl] (BEHF) and PEDOT:PSS as a buffer layer between the emission layers. The
      solution processed multi-layer polymer light-emitting diodes (PLED) were prepared
      by introduction of a water-soluble buffer layer between organic solvent soluble
      layers. We present white organic light-emitting diodes (WOLEDs) that has bilayer
      emission zones. This device exhibits a brightness of 280 cd/m2 and emission
      efficiency of 1.18 cd/A at 12.6 V. The device with a doped PEDOT:PSS layer and a
      thicker blue-emission layer exhibits CIE color coordinates of (0.30, 0.34), which
      is close to the white coordinates of (0.33, 0.33) used by the standard CIE color
      coordinates.

PMID- 22849198
TI  - Effect of ITO surface treatment on organic light emitting diodes.
AB  - Performance of organic light emitting diodes with structure of
      ITO/NPB/NPB:Ir(piq)3/Alq3/Al was studied by inserting MoO3 hole injection layer
      (HIL) and using differently cleaned indium tin oxides (ITOs). High luminance and
      quantum efficiencies were obtained using HIL and highly cleaned ITO. High power
      efficiency was obtained using HIL and conventionally cleaned ITO, while low
      driving voltage was obtained using highly cleaned ITO without HIL.

PMID- 22849199
TI  - Al2O3/TiO2 multilayer passivation layers grown at low temperature for flexible
      organic devices.
AB  - In this study, the permeability of passivation layers consisting of aluminum
      oxide (Al2O3) and titanium oxide (TiO2) was examined. The films were deposited on
      poly(ether sulfone) (PES) substrates via electron cyclotron resonance atomic
      layer deposition (ECR-ALD) at various deposition temperatures. The optimum plasma
      power and deposition temperature were investigated through measurements of the
      refractive index and packing density of the Al2O3 and TiO2 films. A buffer
      layer/multilayer structure was proposed in this study to improve the passivation
      barrier performance. A low water vapor transmission rate (WVTR) of approximately
      5 x 10(-3) g/m2 x day was achieved with two Al2O3/TiO2 stacks with thicknesses of
      40 nm deposited at 80 degrees C. Based on the Arrhenius rate equation, the
      activation energy of water vapor transmission through different passivation
      structures was examined. The activation energies of Al2O3, Al2O3/TiO2, and two
      Al2O3/TiO2 stacks with thicknesses of 40 nm were 51.8, 63.9, and 74.7 kJ/mol,
      respectively.

PMID- 22849200
TI  - C.T. Jackson's 30 November 1845 letter to J.-B.A.L.L. Elie de Beaumont: "What a
      beautiful exemplification of chemical laws..."!

PMID- 22849201
TI  - P. Prithvi Raj, MD, FFARCS: regional anesthesia pioneer.
AB  - At a time when regional anesthesia was a curious alternative, Dr. Raj developed
      techniques to improve the success of the blocks and make regional analgesia more
      acceptable to the average anesthesiologist. His abundant research and numerous
      articles, books, lectures and demonstrations on regional anesthesia and pain
      management have established him as a world leader in the field. He has described
      new blocks and new techniques of doing old blocks. He has described the mechanism
      of action of intravenous regional analgesia. He has improved education and
      training by opening pain centers across the country, each of which has offered
      pain fellowship opportunities. He has founded societies dedicated to research and
      education in regional analgesia and pain management. Regional anesthesia and pain
      management will forever be linked with the name of Dr. Prithvi Raj. University of
      Texas Southwestern Medical Center is proud to have been a part of his early
      development.

PMID- 22849202
TI  - Eponyms in the operating room: careers of six European physicians.

PMID- 22849203
TI  - Analgesia and anesthesia in pre-colonial Africa.

PMID- 22849204
TI  - Royal Operations.

PMID- 22849205
TI  - The history of anesthesia in Roermond 1940-1945--a city in a war zone.
AB  - The Second World War brought much grief to the world. Roermond was at the
      forefront of the war for a period of five months. Before the war, in this part of
      The Netherlands, physicians were more attuned to scientific development taking
      place in Germany than in the United Kingdom. It wasn't until after the war that
      anesthesiology developed as a separate specialty. The impression that the
      hospital records give is that anesthesia was practiced at a far higher level than
      we had always assumed, using a wide variety of drugs and techniques, in spite of
      the fact that there were no professional anesthesiologists at the time. That high
      level was maintained throughout the war in spite of all the hardships.

PMID- 22849207
TI  - An American in Paris in 1846 and 1847: F.W. Fisher (1821-1877).

PMID- 22849206
TI  - C.T. Jackson's 15 October 1846 letter to J.-B.A.L. Elie de Beaumont: Jackson's
      thoughts on Ether Day's Eve?
AB  - As did the previous letter on 30 November 1845 from Charles T. Jackson to J.
      B.A.L. Elie de Beaumont, this 15 October 1846 missive underscores the cordial
      professional relationship between the two geologists. Remarkably, in this "Ether
      Day's Eve" letter, Jackson never reveals whether he had any clue that W.T.G.
      Morton would be publicly demonstrating ether anesthesia for surgery the next
      morning. More importantly, since Elie de Beaumont would play a future pivotal
      role in assigning initial credit for "discovering anesthesia" to his geological
      colleague Jackson, rather than to Morton, letters such as these from November of
      1845 and October of 1846 can only raise more questions about the impartiality of
      Elie de Beaumont.

PMID- 22849208
TI  - Methamphetamine for Hitler's Germany: 1937 to 1945.
AB  - Methamphetamine was synthesized in Germany in 1937 and commercially released in
      1938. It became a popular stimulant for tired night workers and a recreational
      drug for young people until mid-1941 when it became a controlled substance. It
      was abused by the armed forces during World War II when it was distributed by
      some commanding officers (occasionally over the objections of the units'
      physicians) to prevent or treat the fatigue of exhausted troops and thus allow
      them to survive, despite the strict restrictions issued by the Army Inspectorate.
      There is no evidence for the claim that the use of Pervitin was encouraged by the
      Nazi government to create a "superman." In fact the Health Leader L. Conti
      strongly discouraged its use.

PMID- 22849209
TI  - From Amsterdam to Leeds: the travels of the Dutch liquid.

PMID- 22849210
TI  - The origins of the modern pain clinic at the Mayo Clinic.
AB  - In the 1970s the practice of pain management evolved from the isolated
      anesthesiologist practicing pain "on the side" to a multi-disciplinary model. The
      impetus behind this change remains obscure. To understand how this national trend
      occurred locally and to examine national institutional challenges which should be
      reflected at the Mayo Clinic that stimulated the establishment of a modern
      academic pain practice, we interviewed appropriate staff members and reviewed
      relevant departmental meeting notes. Following the 1959 departure of Dr. John
      Lundy from Mayo, Dr. Robert Jones became the primary practitioner of pain
      procedures in addition to his anesthesiology practice. In 1973, close to his
      retirement, Jones wrote a letter to the department chairman, Dr. Richard Theye,
      expressing frustration because this divided practice hindered patient care,
      education, and research opportunities. In 1974 Dr. Lee Nauss joined Mayo upon
      residency completion at Virginia Mason where he received training in regional
      anesthesia and met Dr. John Bonica. Nauss introduced epidural steroid injections,
      which became in such great demand that other anesthesiologists needed to cover
      his rooms. Within two months, Theye asked Nauss to create a stand-alone pain
      clinic. Nauss recruited Dr. Tony Wang and opened the clinic that year. This pain
      clinic increased patient access, improved resident education, allowed for the
      establishment of a fellowship program, and produced ground-breaking research
      (e.g., the human administration of intrathecal morphine). The establishment of
      the pain clinic addressed the deficiencies of a mixed pain and anesthesia
      practice. The pain specialist could now focus attention on and provide better
      access for pain patients, keep current with clinical practice, engage in
      research, and educate future pain specialists.

PMID- 22849211
TI  - The University of Oklahoma: The first independent academic anesthesia department?

PMID- 22849212
TI  - Who was the first to administer general anesthesia in Japan?

PMID- 22849214
TI  - [Urban reform and social hygiene in Santiago de Chile. The liberal techno
      utopianism of Benjamin Vicuna Mackenna (1872-1875)].
AB  - This paper analyzes the main features of the urban reforms by Benjamin Vicuna
      Mackenna in Santiago de Chile between 1872 and 1875. We pay special attention to
      the origin of the objectives of modernization, closely related to the political
      agenda of Latin American elites to create an urban culture (civilization). We
      also analyze the strategies of social defence that these reforms implied. The
      influence of French positivism and the Haussmann project in Paris was very
      important in the Vicuna Mackenna project and its model of a segregated city: the
      "European city" itself,--bourgeois, civilized and hygienic--, which should be
      protected, and the 'African township",--lower-class feral and unhygienic--, whose
      population must be regenerated and colonized.

PMID- 22849213
TI  - P. A. Wilhite and the discovery of ether anesthesia.

PMID- 22849215
TI  - [The hygiene education project of Belisario Penna. 1900-1930].
AB  - This paper aims to present and analyze the hygiene education project of Belisario
      Penna (1868-1939). This physician took part in the public health movement that
      sought, through reforms in public health policy and education, to change the
      conditions that made Brazil a country of the poor, sick and illiterate. We
      describe the main ideas expressed by Penna in the period between 1900 and 1930.
      For this purpose, we use his archive as a privileged source of this physician,
      one of the leading intellectuals of the time.

PMID- 22849216
TI  - [Tierra del Fuego: the scientific-political construction of exclusion and counter
      image of the ideal city dweller].
AB  - Due to its late incorporation into the national State, the social, economic and
      political setting of the Argentine province Tierra del Fuego differed from that
      of the rest of the national territory. In the construction of dependent
      otherness, objectifications and representations were imposed by state-related and
      non-state-related institutions, among other agencies. In this context, the
      Salesian mission of La Candelaria and Ushuaia's Jail for recidivists stand out as
      spaces in which biopolitics was concretised. The native population and criminals
      in Tierra del Fuego were those to be subjugated. The thesis of the extinction of
      the Indian and the simultaneous exaltation of the criminal as the subject of
      progress identified the scientific and political mechanisms by which the
      exclusion of certain social groups (Tierra del Fuego's indigenous population) and
      the inclusion of others (criminals) were regulated.

PMID- 22849217
TI  - [Buenos Aires, between Eros and Thanatos. Prostitution as dysgenic threat (1930
      1955)].
AB  - This paper explores the medical-legal discourse around female prostitution that
      was articulated in Buenos Aires during the first decades of the 20th century. It
      focuses on the use of different ideological resources and on the policies and
      laws that were introduced to gain control over the sex trade and describes
      parallelisms between prostitution, disease and crime. In fact, the capital of
      Argentina was internationally known as a centre of prostitution and white slave
      trafficking, and Jewish participation in these activities allowed the
      consolidation of xenophobic theories. Medicine and law, among other disciplines,
      made important inputs into a simplified approach to this problem.

PMID- 22849218
TI  - [Rome: capital of an empire under the banner of political biology (1936-1942)].
AB  - This paper analyzes the symbolic conformation of Rome and Romanism as important
      factors in the affirmation of the power of fascism, especially after the
      proclamation of the Empire in 1936. Within this framework, it explores the role
      of science in legitimizing the direct correlation of this symbolic universe with
      a praxis that exalted racial superiority inherited from Ancient Rome. It
      investigates the links between the eugenic discourse and the exercise of power
      behind the "biology policy", including fascist organicism and racism. In fact,
      Rome was the essence of an empire that was reborn after fifteen centuries and,
      between its historical legacy and the new scenarios created by fascism for
      disciplining the population, Romanism had to condense all of the merits of the
      race, encouraging military conquests and promoting responsibility for maintaining
      racial purity and avoiding "unwanted miscegenation" with conquered peoples. The
      idea of Romanism also encouraged a continuation of the persecution of Jews
      started in Germany. Hence, science ratified a widespread idea of the Romanization
      as a crusade to impose a force, exaggerated on racial grounds, which integrated
      confidence in environmental factors with a crude biological determinism.

PMID- 22849219
TI  - [Incurable disease in Spain during the 19th century. The Hospital para Hombres
      Incurables Nuestra Senora del Carmen].
AB  - This paper examines the State's assumption of medical care for patients with
      "permanent needs" in 19th century Spain. These patients were the incurably ill,
      the chronically ill and the elderly. This process is contextualized within the
      liberal reforms of the Spanish healthcare system in the reign of Isabel 11 (1833
      1868). The goal of these reforms was the creation and consolidation of a national
      health system that would gradually replace the religious health charities.
      Healthcare reform became necessary due to the increase in migration that started
      in the 1830's and intensified in the 1850's. Traditional care networks formed by
      the family, local community and religious charities were no longer available to
      those who had left their village or town. In addition, many religious charities
      were bankrupted by the seizure of their properties in a programme of
      confiscation. Similar healthcare reform processes were taking place in the United
      Kingdom, France and Germany, among other European countries, and involved
      significant changes in the lives of patients, who became strictly controlled and
      medicalised. My aim was to identify changes in the patients' experience of
      illness through a case study of the living conditions of inmates at the Nuestra
      Senora del Carmen Hospital for Incurable Men, based in Madrid from 1852 to 1949.
      This was one of the institutions devoted to caring for patients with "permanent
      needs" and was under the direct control of the General State Administration.

PMID- 22849220
TI  - [Demographic and epidemiological quantification in Balearic hygienism, 1850
      1930].
AB  - At the end of the 19th century, social medicine promoted the use of
      quantification as a means to evaluate the health status of populations. In
      Majorca, hygienists such as the physicians Enric Fajarnes, Bernat Riera, Antoni
      Mayol and Emili Darder and the civil engineer Eusebi Estada sought a better
      understanding of health status by considering the population growth, the
      demographic and epidemiological profile and the influence of weather on
      mortality. These calculations showed that the Balearic population had a good
      health status in comparison to the population of mainland Spain, although less so
      in the international context. These results were explained by the benevolence of
      the insular climate, a factor that would also guarantee the success of the public
      health reforms proposed.

PMID- 22849221
TI  - [Classifications, agreements and negotiations: bases for the first international
      statistics on mental diseases (Paris 1889)].
AB  - This article discusses the construction of the first international classification
      of mental diseases, specifically created to allow a unified statistics on the
      mentally ill. This classification was discussed and approved at the International
      Congress of Mental Medicine held in Paris in August 1889, in response to a
      request made by the Society of Mental Medicine of Belgium four years earlier. A
      careful reading of this report helps us to understand the role of the
      classification and statistics of pathologies in the field of psychiatric
      medicine. This offers an historical perspective on an issue that remains
      problematic and allows analysis of the time when psychiatric classifications were
      first articulated and subjected to comparative statistical study.

PMID- 22849222
TI  - [An analysis of the first law on contraception in Argentina. The Responsible
      Procreation Programme in the province of La Pampa].
AB  - The passage of a Law requires previous negotiation processes that consider the
      background, arguments, support and the appropriate terminology for approaching
      the issue. The legal domain is a discursive field in which a dual struggle
      develops: to establish designations and to introduce that which the law
      establishes into everyday practice. Hence, conflictive processes are unleashed in
      which social agents are confronted by political parties, by institutions and by
      their own political and subjective identities. This article analyses the
      development of the "1363 Law", which was passed in November 1991 in the
      legislature of La Pampa province (Argentina). This Law created a provincial
      programme for responsible procreation, the first provincial legislation on
      contraception to be established. Although reproduction also involves males,
      special account is taken of speeches referring to females, given that the culture
      superimposes maternity on the female identity and references are therefore
      weighted towards the condition of women. We use the particularity of this case
      and its analytical potential in order to understand others, using as empirical
      material the parliamentary debate and interviews with the author of the Law and
      with key informants. We address the following questions: What was the national
      and provincial context in which the Law on responsible procreation was framed?
      What were the strategies adopted to achieve it? How was contraception articulated
      within the Peronist worldview of women? What meanings did the term "responsible
      procreation" bring into play? Finally, we present a brief assessment of the law's
      application.

PMID- 22849223
TI  - [Madness, public opinion, and mental medicine in the beginning of contemporary
      Spain].

PMID- 22849224
TI  - Opening the border. Steward-Landmark deal signals change in attitude toward for
      profit chains.
AB  - Steward CEO Dr. Ralph de la Torre, left, has had his eye on struggling Landmark
      Medical Center in a neighboring state for a while. But it took action from Rhode
      Island lawmakers for the deal to happen. "There are a number of financially
      distressed hospitals in Rhode Island that should have every option available to
      them as they look for different ways to access capital", Steward said after the
      legislation became law.

PMID- 22849225
TI  - Splitting off. Challenge against ACA wasn't always so clear.

PMID- 22849226
TI  - Rebates on the way. Insurers didn't meet 80-20 standard: Sebelius.

PMID- 22849227
TI  - Pressure builds on Accretive. Congress amps up inquiry amid new allegations.

PMID- 22849228
TI  - Engaging research. First PCORI grants focus on involving patients and families.

PMID- 22849229
TI  - Contraception clash. CHA's opposition may impact reform policy.

PMID- 22849230
TI  - It doesn't compute. Complex, entrenched problems in healthcare continue to defy
      solutions.

PMID- 22849231
TI  - From volume to value. Payment model experiments a bold, significant step to
      transforming industry.

PMID- 22849232
TI  - Value shopping. Employers, payers and patients are looking beyond quality
      measures in their provider comparisons.

PMID- 22849233
TI  - Bundles of quality.

PMID- 22849234
TI  - Aid for first responders.

PMID- 22849235
TI  - Ready for moving day.

PMID- 22849237
TI  - [Merchandising of camphor mothballs in the Meiji era].

PMID- 22849236
TI  - Effects of short-term exposure to air pollution on hospital admissions of young
      children for acute lower respiratory infections in Ho Chi Minh City, Vietnam.
AB  - There is emerging evidence, largely from studies in Europe and North America,
      that economic deprivation increases the magnitude of morbidity and mortality
      related to air pollution. Two major reasons why this may be true are that the
      poor experience higher levels of exposure to air pollution, and they are more
      vulnerable to its effects--in other words, due to poorer nutrition, less access
      to medical care, and other factors, they experience more health impact per unit
      of exposure. The relations among health, air pollution, and poverty are likely to
      have important implications for public health and social policy, especially in
      areas such as the developing countries of Asia where air pollution levels are
      high and many live in poverty. The aims of this study were to estimate the effect
      of exposure to air pollution on hospital admissions of young children for acute
      lower respiratory infection (ALRI*) and to explore whether such effects differed
      between poor children and other children. ALRI, which comprises pneumonia and
      bronchiolitis, is the largest single cause of mortality among young children
      worldwide and is responsible for a substantial burden of disease among young
      children in developing countries. To the best of our knowledge, this is the first
      study of the health effects of air pollution in Ho Chi Minh City (HCMC), Vietnam.
      For these reasons, the results of this study have the potential to make an
      important contribution to the growing literature on the health effects of air
      pollution in Asia. The study focused on the short-term effects of daily average
      exposure to air pollutants on hospital admissions of children less than 5 years
      of age for ALRI, defined as pneumonia or bronchiolitis, in HCMC during 2003,
      2004, and 2005. Admissions data were obtained from computerized records of
      Children's Hospital 1 and Children's Hospital 2 (CH1 and CH2) in HCMC. Nearly all
      children hospitalized for respiratory illnesses in the city are admitted to one
      of these two pediatric hospitals. Daily citywide 24-hour average concentrations
      of particulate matter (PM) < or =10 microm in aerodynamic diameter (PM10),
      nitrogen dioxide (NO2), and sulfur dioxide (SO2) and 8-hour maximum average
      concentrations of ozone (O3) were estimated from the HCMC Environmental
      Protection Agency (HEPA) ambient air quality monitoring network. Daily
      meteorologic information including temperature and relative humidity were
      collected from KTTV NB, the Southern Regional Hydro-Meteorological Center. An
      individual-level indicator of socioeconomic position (SEP) was based on the
      degree to which the patient was exempt from payment according to hospital
      financial records. A group-level indicator of SEP was based on estimates of
      poverty prevalence in the districts of HCMC in 2004, obtained from a poverty
      mapping project of the Institute of Economic Research in HCMC, in collaboration
      with the General Statistics Office of Vietnam and the World Bank. Poverty
      prevalence was defined using the poverty line set by the People's Committee of
      HCMC of 6 million Vietnamese dong (VND) annual income. Quartiles of district
      level poverty prevalence were created based on poverty prevalence estimates for
      each district. Analyses were conducted using both time-series and case-crossover
      approaches. In the absence of measurement error, confounding, and other sources
      of bias, the two approaches were expected to provide estimates that differed only
      with regard to precision. For the time-series analyses, the unit of observation
      was daily counts of hospital admissions for ALRI. Poisson regression with
      smoothing functions for meteorologic variables and variables for seasonal and
      long-term trends was used. Case-crossover analyses were conducted using time
      stratified selection of controls. Control days were every 7th day from the date
      of admission within the same month as admission. Large seasonal differences were
      observed in pollutant levels and hospital admission patterns during the
      investigation period for HCMC. Of the 15,717 ALRI admissions occurring within the
      study period, 60% occurred in the rainy season (May through October), with a peak
      in these admissions during July and August of each year. Average daily
      concentrations for PM10, O3, NO2, and SO2 were 73, 75, 22, and 22 microg/m3,
      respectively, with higher pollutant concentrations observed in the dry season
      (November through April) compared with the rainy season. As the time between
      onset of illness and hospital admission was thought to range from 1 to 6 days, it
      was not possible to specify a priori a single-day lag. We assessed results for
      single-day lags from lag 0 to lag 10, but emphasize results for an average of lag
      1-6, since this best reflects the case reference period. Results were robust to
      differences in temperature lags with lag 0 and the average lag (1-6 days);
      results for lag 0 for temperature are presented. Results differed markedly when
      analyses were stratified by season, rather than simply adjusted for season. ALRI
      admissions were generally positively associated with ambient levels of PM10, NO2,
      and SO2 during the dry season (November-April), but not the rainy season (May
      October). Positive associations between O3 and ALRI admissions were not observed
      in either season. We do not believe that exposure to air pollution could reduce
      the risk of ALRI in the rainy season and infer that these results could be driven
      by residual confounding present within the rainy season. The much lower
      correlation between NO2 and PM10 levels during the rainy season provides further
      evidence that these pollutants may not be accurate indicators of exposure to air
      pollution from combustion processes in the rainy season. Results were generally
      consistent across time-series and case-crossover analyses. In the dry season,
      risks for ALRI hospital admissions with average pollutant lag (1-6 days) were
      highest for NO2 and SO2 in the single-pollutant case-crossover analyses, with
      excess risks of 8.50% (95% CI, 0.80-16.79) and 5.85% (95% CI, 0.44-11.55)
      observed, respectively. NO2 and SO2 effects remained higher than PM10 effects in
      both the single-pollutant and two-pollutant models. The two-pollutant model
      indicated that NO2 confounded the PM10 and SO2 effects. For example, PM10 was
      weakly associated with an excess risk in the dry season of 1.25% (95% CI, -0.55
      to 3.09); after adjusting for SO2 and O3, the risk estimate was reduced but
      remained elevated, with much wider confidence intervals; after adjusting for NO2,
      an excess risk was no longer observed. Though the effects seem to be driven by
      NO2, the statistical limitations of adequately addressing collinearity, given the
      high correlation between PM10 and NO2 (r = 0.78), limited our ability to clearly
      distinguish between PM10 and NO2 effects. In the rainy season, negative
      associations between PM10 and ALRI admissions were observed. No association with
      O3 was observed in the single-pollutant model, but O3 exposure was negatively
      associated with ALRI admissions in the two-pollutant model. There was little
      evidence of an association between NO2 and ALRI admissions. The single-pollutant
      estimate from the case-crossover analysis suggested a negative association
      between NO2 and ALRI admissions, but this effect was no longer apparent after
      adjustment for other pollutants. Although associations between SO2 and ALRI
      admissions were not observed in the rainy season, point estimates for the case
      crossover analyses suggested negative associations, while time-series (Poisson
      regression) analyses suggested positive associations--an exception to the general
      consistency between case-crossover and time-series results. Results were robust
      to differences in seasonal classification. Inclusion of rainfall as a continuous
      variable and the seasonal reclassification of selected series of data did not
      influence results. No clear evidence of station-specific effects could be
      observed, since results for the different monitoring stations had overlapping
      confidence intervals. In the dry season, increased concentrations of NO2 and SO2
      were associated with increased hospital admissions of young children for ALRI in
      HCMC. PM10 could also be associated with increased hospital admissions in the dry
      season, but the high correlation of 0.78 between PM10 and NO2 levels limits our
      ability to distinguish between PM10 and NO2 effects. Nevertheless, the results
      support the presence of an association between combustion-source pollution and
      increased ALRI admissions. There also appears to be evidence of uncontrolled
      negative confounding within the rainy season, with higher incidence of ALRI and
      lower pollutant concentrations overall. Exploratory analyses made using limited
      historical and regional data on monthly prevalence of respiratory syncytial virus
      (RSV) suggest that an unmeasured, time-varying confounder (RSV, in this case)
      could have, in an observational study like this one, created enough bias to
      reverse the observed effect estimates of pollutants in the rainy season. In
      addition, with virtually no RSV incidence in the dry season, these findings also
      lend some credibility to the notion that RSV could influence results primarily in
      the rainy season. Analyses were not able to identify differential effects by
      individual-level indicators of SEP, mainly due to the small number of children
      classified as poor based on information in the hospitals' financial records.
      Analyses assessing differences in effect by district-level indicator of SEP did
      not indicate a clear trend in risk across SEP quartiles, but there did appear to
      be a slightly higher risk among the residents of districts with the highest
      quartile of SEP. As these are the districts within the urban center of HCMC,
      results could be indicative of increased exposures for residents living within
      the city center. (ABSTRACT TRUNCATED)

PMID- 22849238
TI  - [Historical consideration of the outbreaks induced by adverse drug reactions in
      Japan and the necessary preventive schemes depending on the accurate use of drug
      informatics].

PMID- 22849239
TI  - [The etymological study of mudan and shaoyao in Chinese herbal medicine (Part 1).
      A Comparative Study of mudan and Ardisia spp].
AB  - In China, present-day, the tree peony is not only being used in traditional
      medicine, but has also been extolled to a status equivalent to that of a national
      flower. This plant is now called mudan in the Chinese language, although it seems
      disputable what plant mudan originally referred to. Particularly, the botanical
      accounts on mudan in the Newly Revised Canon of Materia Medica (Xinxiu Bencao)
      contain some discrepancies regarding the actual features of the tree peony. The
      primary investigation of this issue has already been published, and reached the
      conclusion that mudan used to refer to Ardisia spp. However, further
      verifications looking at different aspects are required. This paper intends to
      show that mudan and Ardisia ssp. have shared drug properties and usages as listed
      in various Chinese medical texts. These consistencies certify that mudan can
      possibly be replaced with Ardisia ssp., when we utilize the pre-Tang dynasty's
      prescriptions. In addition, there is further significant evidence for the notion
      that mudan used to refer to Ardisia ssp.

PMID- 22849240
TI  - [Historical study on traditional Chinese formulations and crude drugs used for
      gouty arthritis].
AB  - Rates of gouty arthritis with hyperuricemia have increased recently as it has
      become a lifestyle-related disease. We reviewed historical treatments for pain
      due to gouty arthritis in traditional Chinese medical books, with special
      interest in pathological causes, including dietary and drinking habits, as well
      as the frequency of crude drugs used in historical prescriptions. From the
      present historical survey, we showed that six traditional terms may be equivalent
      to modern gouty arthritis and that the "Manbyokaishun," a formulary edited in the
      16th century in China, included medical information for gouty arthritis.
      Furthermore, the 46 prescriptions, including Sokeikakketsuto, mentioned in the
      "Manbyokaishun," were selected as likely treatments for gouty arthritis. The most
      common crude drugs in the 46 prescriptions were aconite root, angelica root,
      cinnamon bark, peony root and saposhnikovia root. The inhibitory activity of
      these crude drugs extracts against xanthine oxidase was investigated. Angelica
      root and saposhnikovia root showed more potent inhibitory activity (20% at 250
      microg/mL) than aconite root (16%), notopterygium rhizome (15%) and cinnamon bark
      (12%).

PMID- 22849241
TI  - [Analytical chemistry in works of Maria Sklodowska-Curie].
AB  - Maria Sklodowska-Curie--a Nobel Prize winner in chemistry--the elements of
      learning of chemistry gained just by a dint of work of more than ten months in
      Warsaw in the Institute of Industry and Agriculture Museum. The Nobel Prize
      concerned a contribution to the progress of chemistry through the discovery of
      radium and polonium, separation of radium and study of properties of this amazing
      element. It was awarded for an extremely arduous work, during which the chemical
      reactions being the principles of analytical chemistry were realized. Unlike to a
      typical analytical procedure, an initial attempt here was the thousands of
      kilograms of uranium ore: pitchblende. The final effect was small amounts of new
      elements: polonium and radium. Both the knowledge and the intuition of the
      researcher let her have a triumph. The difficulties she experienced because the
      properties of the searched chemical elements could only be evaluated thanks to
      the knowledge on other chemical elements. A significant achievement was the
      determination of the samples by means of radioactivity measurement, which gave
      rise to radiochemical analytical methods. An extreme analytical precision was
      demanded in multiple processes of fractional crystallization and precipitation
      which finally led to the calculation of the atomic mass of radium.

PMID- 22849242
TI  - [Maria Sklodowska-Curie and Piotr Curie an epoch-makingin year 1898].
AB  - For many reasons the year 1898 was unusual for Maria Sklodowska-Curie and her
      husband. After defining the subject of the doctoral thesis and choosing Henri
      Becqerel as thesis supervisor, Maria started intensive experimental work. In the
      allotted room called storeroom, in conditions that were far too inadequate, they
      managed to put up a unique measuring equipment composed of instruments whose
      originator was Pierre Curie. In the ionization chamber and in the piezoelectric
      quartz charges formed, whose mutual neutralization was shown by the quadrant
      electrometer. Ionization current, which was measured quantitatively, was
      proportional to the radiation of the sample. Studying many elements, their
      compounds and minerals enabled Maria to state that uranium is not the only
      element endowed with the power of radiation; the second one turned out to be
      thorium. Anomaly detected in the radiation of uranium minerals made it possible
      for Maria to draw an extremely important conclusion: radioactive uranium and
      thorium are not the only elements endowed with such an attribute. Pitchblende,
      which was studied by the Curie couple, had to contain also other radioactive
      substances. Gustave Bemont also participated in the chemical analysis of the
      uranium ore and it is worth reminding that he was involved in the discovery of
      polonium and uranium. The phenomenon of radioactivity couldn't have been
      explained if it was not for the sources of strong radioactivity. Those sources
      undoubtedly could have been the discovered elements but their scanty content in
      the uranium ore made their isolation very difficult and laborious. Access to
      industrial remains after procession of pitchblende from Jachymov (Sankt
      Joachimstahl), obtained owing to the mediation of Eduard Suess, provided the
      source of this raw material. From it, in a shack also called le hangar, the Curie
      couple isolated the first samples of the radium salt. This element, later
      extracted by discoverers on a grand scale and handed over in a various forms to
      researchers and institutions, became a foundation of physics and chemistry of
      radioactive elements.

PMID- 22849243
TI  - [Maria Sklodowska-Curie--her chemistry at the centenary of the second Nobel
      Prize].
AB  - The article presents from the perspective of one hundred years the work of Maria
      Curie-Sklodowska, which in many cases was ahead of the state of knowledge of the
      time. It opened new horizons and for this reason we made many digressions. The
      fact of awarding her the Nobel Prize twice is a sensation enough to present the
      values of careful activity of the Nobel Prize Committee that emphasizes the
      importance of Maria's achievements. A significant element of Maria Sklodowska
      Curie's achievements was still mysterious character of the radiation in her time,
      and only chemical approach made it possible to organise the phenomena and explain
      the origin of the radiation. The essence of the research was an arduous
      separation of components following the track of growing radiation of successive
      fractions of preparations. This research was a start of the technology of
      educement of dispersed elements in great mass of materials. We underline the
      paramount role of the chemical research Maria Sklodowska conducted while still in
      Warsaw in the laboratories of the Museum of Industry and Agriculture under the
      guidance of an excellent chemist Jozef Jerzy Boguski. Her research in Paris was
      the origin of the semi-commercial scale in chemistry and setting aside a special
      shed outside the university building was the beginning of the institutes that now
      function beyond universities and are key element of scientific and technical
      progress. Technology of splitting developed by Maria Sklodowska-Curie was applied
      also by other radiochemists, e.g. By Otto Hahn. Lively movement in radiochemistry
      of her lifetime resulted in Maria's disputes with e.g. German chemist Marckwald,
      who questioned the originality of polonium. The scientific disputes like this one
      Maria won triumphantly although in several others she had to accept opponents'
      argument, as in the case of radon. Her experiments were planned with utmost
      rationality as it was with the rejection of the hypothesis saying that
      radioactivity was transferred from the outer space or from the sun. A great part
      of Maria Sklodowska-Curie's work was connected with biology which was
      demonstrated by describing in mathematical terms, for the first time in the
      history of radiobiology, nonexistent at that time, of the phenomenon of
      inactivation of bacteria by ionizing radiation. We emphasize difficult conditions
      for the health of the radiochemists of the time but we don't find any proof that
      there was any influence of ionizing radiation on Maria's health. She must have
      absorbed much greater doses of radiation during her heroic work in the mobile
      radiological surgery at the front of the 1st World War. We don't think it's
      appropriate to speculate rashly about contamination with alpha emitters.
      Unfortunately, due to her family's protest it was impossible to collect samples
      of remains before their relocation to the Pantheon in Paris.

PMID- 22849244
TI  - [The development of radiation technologies since Maria Sklodowska-Curie].
AB  - The article was written on the occasion of the 100. anniversary of the Nobel
      Prize in Chemistry awarded to Maria Sklodowska-Curie. The United Nations General
      Assembly honoured this event by announcing the year 2011 the International Year
      of Chemistry. Maria Sklodowska-Curie was i.a. the initiator of radiation
      chemistry, a branch of science analyzing the chemical effects that matter shows
      when exposed to ionizing radiation. The development of this branch resulted in
      radiation technologies' applications in many fields of industry, medicine,
      agriculture, protection of the environment, space research and science. Our point
      of departure was the article Sur l'etude des courbes de probabilite relatives a
      l'action des rayons X sur les bacilles that Maria Sklodowska-Curie published in
      1929 in the Bulletin of the Academie des sciences. In this study, she presented-
      for the first time ever--the curves of the so called radiation inactivation, i.e.
      the relationship between the bacteria life expectancy and the dose of radiation
      absorbed by it. From the today's point of view, it can be stated that the
      researcher laid the foundations of the methods of radiation sterilization and
      material processing by means of radiation. In this context, we recall the history
      of the first accelerator installation devised and built in 1968 at the Institute
      of Nuclear Chemistry and Technology in Warsaw. Basing on experiences with the
      linear electron accelerator, the LAE 13/9 was completed in 1992 as the so far
      only Polish industrial installation for radiation sterilization of medical
      products and transplants as well as for food irradiation.

PMID- 22849245
TI  - [Early career of Michael Sendivogius].
AB  - One of the most influential alchemical authors of the early modern period was
      Michael Sendivogius whose early life is shrouded in mystery. He may be labelled
      the most famous Polish scientific writer between Copernicus and Marie Sklodowska
      Curie, but because of the difficulties involved in researching the biography of
      any alchemist, there has been relatively little interest in him among Polish
      historians. The early work of Roman Bugaj (author of the still fundamental
      monograph) and Wlodzimierz Hubicki (who made his research available to the
      international community) has been continued only by the English-born Zbigniew
      Szydlo and the author of this article. The roots of many legends about
      Sendivogius were three mid-17th century short biographies, none of which is
      trustworthy, so it is crucial to verify the received myth and the version
      constructed in the 1960's and 1970's with primary sources and evidence from the
      recent "new historiography of alchemy". The present article examines them in the
      light of newly discovered sources and reinterpretation of the old ones. The
      genealogy of the Sedzimir family is discussed at length to show that Sendivogius
      most probably was not its member but only a pretender in order to assume (or
      prove) the status of a nobleman. Several possible hypotheses about his origins
      are presented. He is known to have studied at three universities (Leipzig, Vienna
      and Altdorf) but authors of early panegyrics dedicated to Sendivogius list more
      universities which he may have attended. The most interesting is that of
      Cambridge, listed as the first one, because practically no Poles or Czechs went
      there at the time. Finally, his marriage to Veronica Stiebar, a wealthy widow of
      a Franconian knightly family, and her interesting family relationships (links to
      Erasmus, Camerarius, Paracelsus and the original Doctor Faustus) are discussed.
      The period covered is that before Sendivogius moved to Prague in about 1597,
      having already been a courtier of Rudolf II since early 1594.

PMID- 22849246
TI  - Unearthing Benny the Bulldozer: the culture of clearance in postwar children's
      books.

PMID- 22849247
TI  - Veterinary medicine as portrayed on postcards.

PMID- 22849248
TI  - "A plea for the prostate": doctors, prostate dysfunction, and male sexuality in
      late 19th- and early 20th-century Canada.
AB  - Historical examinations of medical discourse concerning male sexuality have
      focused on the perceived linkage between masturbation and sexual neurasthenia.
      However, more tangible conditions such as prostatic hypertrophy were also linked
      to the sexual misconduct of young and old men. This paper examines both the
      medical discourse concerning prostatic hypertrophy and how the development of
      treatment was influenced by contemporary concerns with both sexuality and
      masculinity. It argues that mainstream doctors moved away from the Victorian
      preoccupation with the dangers of illicit sexuality and increasingly regarded the
      restoration of sexual function as being in the best interests of their patients.
      This view was particularly evident in their quest for an operative method that
      would cure prostatic hypertrophy while preserving potency.

PMID- 22849249
TI  - [Ethical aspirations and the reality of medical practice at the end of the Ancien
      Regime].
AB  - At the end of the 18th century, economic survival was difficult for physicians.
      The medical market was crowded and to build (and seduce) a clientele, they had to
      pay particular attention to their appearance. Being well dressed and travelling
      by horse or in a carriage was necessary to demonstrate that they had a good
      reputation and were a "good" doctor. However, this still did not guarantee
      financial security for the doctor and his family. In an era when medical fees
      were only just beginning to be discussed, it was difficult to know how to bill
      patients and how to get paid. At the same time, the first texts on medical ethics
      appeared, insisting on modesty, authenticity, delicacy, and sincerity. In this
      article, by exploring personal archives and printed moral prescriptions, I will
      suggest that there were tensions between the everyday difficulties of medical
      practice and the recommendations on medical ethics, tensions that had
      consequences for the patient-doctor relationship.

PMID- 22849250
TI  - Sairey Gamps, feminine nurses and greedy monopolists: discourses of gender and
      professional identity in the Lancet and the British Medical Journal, 1886-1902.
AB  - The British debate over midwife registration in the late 19th and early 20th
      centuries was highly gendered. Focusing on the period between the 1886 Medical
      Act and the 1902 Midwives Act, this article uses the content from the Lancet and
      the British Medical Journal, the two main general medical publications of the
      time, to explore the complex ways that gender works through other categories such
      as class and race to create professional identity. Specifically this article
      demonstrates how man-midwives used gendered language to help create identities
      for themselves, female midwives, and other rivals in order to legitimize their
      own professional identity and practice and to delegitimize the professional
      identities of their competition.

PMID- 22849251
TI  - "The blood fights on in other veins": Norman Bethune and the transfusion of
      cadaver blood in the Spanish Civil War.
AB  - During the Spanish Civil War, Dr. Norman Bethune instituted a research laboratory
      to determine whether the blood from cadavers could be transfused into wounded
      soldiers and civilians at the front. Dr. Herman J. Muller joined him in this
      effort carrying out extensive experimentation into the technique and practice of
      such transfusions. At the same time, Bethune was in frequent contact with Dr.
      Reginald Saxton who later publicly advocated that the Spanish government should
      organize a large-scale supply of cadaver blood to the front-line hospitals.
      Recent evidence suggests that Saxton carried out cadaveric transfusions to an
      extent not previously recognized.

PMID- 22849252
TI  - Feminization of Canadian medicine: voices from the second wave.
AB  - In 2009 a Globe and Mail pundit claimed that the current doctor shortage stems
      from increasing numbers of women in medicine. This opinion is widely held,
      despite articulate opposition from medical deans who characterized it as a new
      variant of the old "sexist blame game" (CMAJ 2008). In this ambivalent climate,
      we interviewed 10 women who entered the Canadian profession between 1945 and
      1960, when strict limits on female students were established in most schools.
      Using semi-structured, in-person and telephone interviews, we found that they
      worked as much as their male colleagues. Several also raised three to five
      children; and negotiation of the domestic sphere usually fell to them. Most
      worked past age 65, and two are still working well into their eighties. Our
      findings will be set in the context of the existing literature on women in
      medicine. We will also examine the results of surveys on physicians' working
      hours, in which all specialties show a decline, including those that have not
      been feminized. We conclude that the women who entered the profession between
      1945 and 1960 did not contribute to the current doctor shortage.

PMID- 22849253
TI  - "The older staff, myself included, we were pretty institutionalized ourselves":
      authority and insight in practitioner narratives of psychiatric
      deinstitutionalization in Prairie Canada.
AB  - In the early 1960s, Canada's provinces began radically to reduce the in-patient
      populations of their psychiatric services. This was part of a wider project of
      trans-institutionalization through which vulnerable people and those who cared
      for them were shifted across institutional contexts within Canada's evolving
      welfare state apparatus. This article draws on interviews with Psychiatric Nurses
      who worked through the transformative mental health reforms of the 1960s and
      1970s, and it makes a case for practitioner history. Practitioner narratives
      offer a window on the vital tensions between the manifest and the latent
      functions of welfare institutions, between the impulse to support and the impulse
      to control, and between paternalism and respect for the rights of the mentally
      ill. It draws upon the authority of practitioners who, retrospectively, have
      gained insight into their involvement with prior regimes of caring and control
      and have come to discern institutional logics previously so hegemonic as to have
      been largely invisible to them.

PMID- 22849254
TI  - The social integration of the mentally ill in Quebec prior to the Bedard Report
      of 1962.
AB  - This article on the first initiatives of social integration of the mentally ill,
      using the example of Saint-Jean-de-Dieu Hospital, explores the implementation of
      dehopsitalization (the transition between hospital and community care) in the
      early decades of the 20th century. Our study is part of the recent
      historiographical stream that offers a reinterpretation of the period just prior
      to the Quiet Revolution in Quebec. We aim to contribute to this research by
      showing that the policies, strategies, and practices of the Sisters of Providence
      and the psychiatrists of Saint-Jean-de-Dieu already comprised a
      deinstitutionalization system that was reintegrating patients into their families
      as early as the 1910s--half a century before the first wave of
      deinstitutionalization of the 1960s was orchestrated by the authors of the Bedard
      Report.

PMID- 22849255
TI  - "He is still unwanted": women's assertions of authority over abortion in letters
      to the Royal Commission on the Status of Women in Canada.
AB  - Throughout the 1960s, the public abortion debate was dominated by men. While
      women's voices were not absent, they are harder to locate. This article
      highlights one forum in which women eloquently expressed their feelings about
      abortion. In submissions to the Royal Commission on the Status of Women in
      Canada, women demonstrated their "right" to speak on the issue in many ways,
      including by sharing their experiences as mothers or with unplanned and unwanted
      pregnancies; referencing their professional lives, especially in care giving
      fields; and drawing moral authority from or opposing religious beliefs. This
      article analyzes women's efforts to convey their authority to speak to the
      legality of abortion, highlighting a component of the 1960s abortion law reform
      discussion often overlooked.

PMID- 22849256
TI  - No consensus. Healthcare systems slam NQF over support of readmissions measure.
AB  - A recent decision by the National Quality Forum endorsing a measure on
      readmissions has a group of large hospitals and systems crying foul and
      criticizing the group's process. "It's very rare that we don't have overwhelming
      support for measures when they're endorsed because there are so many
      opportunities to have issues raised and resolved along the way... This is an
      unusual case," says Dr. Helen Burstin, left, of the NQF.

PMID- 22849257
TI  - Expecting a bounce. Spending projected to soar as ACA takes effect.

PMID- 22849258
TI  - 'Model legislation'. States, ALEC take reform into their own hands.

PMID- 22849259
TI  - Pain and profit. The healthcare industry thrives, but many Americans struggle.

PMID- 22849260
TI  - Not secular. Tradition and law dictate special status for Catholic healthcare.

PMID- 22849261
TI  - Bonus round. Compensation climbs for association execs, and the Supreme Court
      could fuel the trend regardless of its verdict.

PMID- 22849262
TI  - Equipping EMS. New technologies help improve patient care, ease burden on
      staffers.

PMID- 22849263
TI  - Antimicrobial resistance in animal and public health. Preface.

PMID- 22849264
TI  - Antimicrobial resistance in animal and public health: introduction and
      classification of antimicrobial agents.
AB  - Bacteria have a remarkable ability to adapt, evolve and survive by developing
      resistance to therapeutic compounds. This ability is also shared by other
      pathogenic agents such as viruses, fungi, and parasites. Even when focusing on
      bacterial resistance only, this phenomenon is quite complex to analyse due to the
      diversity of animal species, the diversity of rearing environment, the number of
      antimicrobial classes available and the diversity of pathogenic bacteria
      involved. This introductory paper includes developments on the place of antiviral
      compounds in veterinary medicine and a classification of antimicrobials used in
      food-producing animals.

PMID- 22849265
TI  - Antimicrobial resistance: a complex issue.
AB  - The discovery of antibiotics represented a turning point in human history.
      However, by the late 1950s infections that were difficult to treat, involving
      resistant bacteria, were being reported. Nowadays, multiresistant strains have
      become a major concern for public and animal health. Antimicrobial resistance is
      a complex issue, linked to the ability of bacteria to adapt quickly to their
      environment. Antibiotics, and antimicrobial-resistant bacteria and determinants,
      existed before the discovery and use of antibiotics by humans. Resistance to
      antimicrobial agents is a tool that allows bacteria to survive in the
      environment, and to develop. Resistance genes can be transferred between bacteria
      by horizontal transfer involving three mechanisms: conjugation, transduction and
      transformation. Resistant bacteria can emerge in any location when the
      appropriate conditions develop. Antibiotics represent a powerful selector for
      antimicrobial resistance in bacteria. Reducing the use of antimicrobial drugs is
      one way to control antimicrobial resistance; however, a full set of measures
      needs to be implemented to achieve this aim.

PMID- 22849266
TI  - Susceptibility testing methods, resistance and breakpoints: what do these terms
      really mean?
AB  - The Clinical and Laboratory Standards Institute and the European Committee on
      Antimicrobial Susceptibility Testing can be considered the major international
      contributors to antimicrobial susceptibility testing. In this review, the author
      considers the differences between the respective organisations, examines the
      terminology used in antimicrobial susceptibility testing and argues for an urgent
      need to harmonise these definitions. While this may seem somewhat surprising, the
      terminology used to define resistance does differ. In this context, attention is
      given to the trend for 'resistance' to be defined by the epidemiological cut-off
      value, rather than by the long-established clinical breakpoint. The author goes
      on to discuss susceptibility testing methodologies and present an approach to
      setting clinical breakpoints.

PMID- 22849267
TI  - Antimicrobial agents targeting bacterial cell walls and cell membranes.
AB  - Antimicrobial agents that target the bacterial cell wall or cell membrane have
      been used effectively for the past 70 years. Among the agents that inhibit
      bacterial cell wall synthesis, the beta-lactam antibiotics have emerged into
      broad-spectrum agents that inhibit most pathogenic bacteria, but are now being
      threatened by the rapid spread of drug-inactivating beta-lactamases.
      Glycopeptides still retain high activity against staphylococci, but resistance
      among the enterococci has become a major problem. Recently, fosfomycin has been
      used in the treatment of multidrug-resistant Gram-negative bacteria. Daptomycin,
      which targets both membrane function and peptidoglycan synthesis, is especially
      effective in treating staphylococcal infections. The polymyxin antibiotics that
      target cell membranes are being used more frequently to treat multidrug-resistant
      Gram-negative infections. The ionophore antibiotics, used in veterinary medicine,
      target membranes in many microbial and animal species. Although increasing
      resistance is a continuing concern, these classes of bactericidal agents can
      provide highly effective antibiotics.

PMID- 22849268
TI  - Antibiotics that affect the ribosome.
AB  - The ribosome is a major bacterial target for antibiotics. Drugs inhibit ribosome
      function either by interfering in messenger RNA translation or by blocking the
      formation of peptide bonds at the peptidyl transferase centre. These effects are
      the consequence of the binding of drugs to the ribosomal subunits. Various
      mechanisms, including enzymatic detoxification, target alteration (ribosomal
      [r]RNAs and ribosomal proteins) and reduced accumulation (impermeability and
      efflux) are involved in bacterial resistance to protein synthesis inhibitors. The
      fact that some positions in rRNA participate in the binding of antibiotics
      belonging to distinct families explains why bacteria have developed mechanisms
      that can lead to cross-resistance.

PMID- 22849269
TI  - Antimicrobials that affect the synthesis and conformation of nucleic acids.
AB  - Several antimicrobials act by inhibiting the synthesis of nucleic acids
      (rifamycins, sulfamides, diaminopyridines), modifying their conformation
      (quinolones, coumarins) or causing irreversible lesions (nitroimidazoles,
      nitrofurans). The resistance mechanisms are: a reduction in intracytoplasmic
      accumulation, modification of the target or the production of a new low-affinity
      target and, more rarely, enzyme inactivation. Although the mechanisms affecting
      the targets are specific to each family and can lead to high-level resistance,
      the reduced permeability of the membrane and the increased efflux are non
      specific and result in low-level cross-resistance between several families. The
      genetic mediation is usually chromosomal for rifamycins and quinolones, although
      plasmid-mediated resistant genes have been observed. On the other hand, for
      sulfamides and trimethoprim, plasmid-borne genes are frequent. Resistance to
      nitroimidazoles and nitrofurans is still not widely understood.

PMID- 22849270
TI  - Cross-resistance between biocides and antimicrobials: an emerging question.
AB  - The widespread use of biocides, and their resulting dissemination in the
      environment, can contribute to adaptations in bacteria leading to the development
      of low-level susceptibility to antibacterial agents. The mechanisms of resistance
      in bacteria are similar for both antimicrobials and biocides, and exposure to
      biocides can result in cross-resistance to antibacterial agents. Resistance
      mechanisms altering the activity of biocide and antibiotic molecules are
      discussed with regard to regulation and mode of action in the light of laboratory
      studies of induced resistance. It is clear that in order to preserve their
      activity and avoid the development of possible cross-resistance, prudent use of
      antibacterial agents is to be strongly recommended, not only in clinical settings
      but also in veterinary and agricultural and other applications.

PMID- 22849271
TI  - Surveillance and monitoring of antimicrobial resistance and antibiotic
      consumption in humans and animals.
AB  - Surveillance and monitoring studies of antimicrobial resistance in bacteria of
      human and animal origin and antimicrobial consumption in humans and animals have
      been conducted in various countries throughout the world. In the veterinary
      field, in particular, programmes have been installed which target bacteria of
      zoonotic, foodborne and/or veterinary relevance. Each year, the European
      Surveillance of Veterinary Antimicrobial Consumption project summarises and
      evaluates antimicrobial consumption in ambulatory and hospital care in many
      European countries. In contrast, antimicrobial consumption data in veterinary
      medicine are available from only a few countries and the type of information that
      is collected or reported varies. To address this challenge, the European
      Surveillance of Veterinary Antimicrobial Consumption project was launched by the
      European Medicines Agency in September 2009 and has just published its first
      report. This comparison of the different studies for surveillance and monitoring
      of antimicrobial resistance and antimicrobial consumption in humans and animals
      shows the need to improve harmonisation.

PMID- 22849272
TI  - Human use of antimicrobial agents.
AB  - Antibiotics have increased life expectancy. Self-medication, even over the
      Internet, occurs in many countries where antibiotics are classified as
      prescription-only medicines. Collateral damage caused by antibiotic use includes
      resistance, which could be reduced if the inappropriate use of antibiotics that
      takes place globally, especially in low-income countries, could be prevented.
      Surveillance of antimicrobial resistance can recognise trends in resistance
      patterns and novel resistances. Surveillance of antimicrobial consumption can
      identify and target practice areas for quality improvement, both in the community
      and in healthcare institutions. Antimicrobial stewardship initiatives and
      infection control programmes play an important role in decreasing inappropriate
      use and halting dissemination of resistance. Education of professionals and the
      public should focus on changing behaviour rather than exclusively increasing
      knowledge, as the latter could have a paradoxical effect by increasing demand and
      prescription. Behaviour change should target all prescribers, including
      veterinarians, since microbes know no boundaries between animals and humans and
      are capable of exchanging resistance genes.

PMID- 22849273
TI  - Antimicrobial stewardship: lessons from human healthcare.
AB  - This paper focuses on antimicrobial stewardshipin human healthcare, and some
      concepts possibly transferable to veterinary medicine. Antimicrobial stewardship
      is a multidisciplinary effort to reduce antimicrobial resistance in human
      pathogens, when future drug development is dwindling. These strategies encourage
      healthcare staff to use antimicrobials prudently and, when needed, for as short a
      duration and with as narrow a spectrum as possible. Various methods are involved
      in stewardship within the healthcare setting, often implemented simultaneously,
      which sometimes makes evaluation of specific measures difficult. All healthcare
      workers must accept responsibility for stewardship, although the role of
      infectious diseases physicians, microbiologists, pharmacists and infection
      control practitioners is crucial, as are appropriate surveillance systems and
      information technology. Support from management and government is also
      beneficial. Considering the frequent use of antimicrobials in animals, it would
      seem sensible to apply a similarly critical approach to conserve the efficacy of
      the antimicrobials still available, now and in the future.

PMID- 22849274
TI  - Use of antimicrobial agents in livestock.
AB  - Antimicrobial agents, especially antibacterial agents, are used throughout the
      world, across a diverse array of extensive and intensive livestock production
      systems, to protect the health and welfare of livestock and to improve their
      performance. While some agents that are used in livestock belong to classes that
      have no counterpart in human medicine, this is not the case for the most widely
      used agents: the tetracyclines, penicillins, macrolides and sulphonamides. Many
      bacterial diseases of livestock cause devastating losses of animal life and
      productivity. As a result, their keepers can lose their livelihoods and see a
      dramatic reduction in income, so there is often a great sense of urgency to treat
      affected animals early. However, there are a large number of bacterial pathogens
      that cause disease and it is frequently difficult to reach a conclusive diagnosis
      prior to instituting treatment. There are many ways in which existing uses of
      antimicrobial agents can be improved, amongst the most important are increased
      utilisation of veterinary professional services, the introduction of enhanced
      infection control measures, improved point-of-care diagnostic tests, and the
      application of physiologically based population pharmacokinetic-pharmacodynamic
      modelling.

PMID- 22849275
TI  - Use of antimicrobial agents in aquaculture.
AB  - The aquaculture industry has grown dramatically, and plays an important role in
      the world's food supply chain. Antimicrobial resistance in bacteria associated
      with food animals receives much attention, and drug use in aquaculture is also an
      important issue. There are many differences between aquatic and terrestrial
      management systems, such as the methods used for administration of drugs. Unique
      problems are related to the application of drugs in aquatic environments.
      Residual drugs in fish products can affect people who consume them, and
      antimicrobials released into aquatic environments can select for resistant
      bacteria. Moreover, these antimicrobial-resistant bacteria, or their resistance
      genes, can be transferred to humans. To decrease the risks associated with the
      use of antimicrobials, various regulations have been developed. In addition, it
      is necessary to prevent bacterial diseases in aquatic animals by vaccination, to
      improve culture systems, and to monitor the amount of antimicrobial drugs used
      and the prevalence of antimicrobial-resistant bacteria.

PMID- 22849276
TI  - Use of antibiotics in plant agriculture.
AB  - Antibiotics are essential for control of bacterial diseases of plants, especially
      fire blight of pear and apple and bacterial spot of peach. Streptomycin is used
      in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is
      limited to only a few countries. Springtime antibiotic sprays suppress pathogen
      growth on flowers and leaf surfaces before infection; after infection,
      antibiotics are ineffective. Antibiotics are applied when disease risk is high,
      and consequently the majority of orchards are not treated annually. In 2009 in
      the United States, 16,465 kg (active ingredient) was applied to orchards, which
      is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are
      active on plants for less than a week, and significant residues have not been
      found on harvested fruit. Antibiotics have been indispensable for crop protection
      in the United States for more than 50 years without reports of adverse effects on
      human health or persistent impacts on the environment.

PMID- 22849277
TI  - Clinical impact of antimicrobial resistance in humans.
AB  - The dramatic rise in the number and spread of resistant bacterial species
      continues. This involves not only bacteria that cause infections in the
      healthcare sector but also those that originate in the community. Antibiotic
      resistance rates are rising in almost all bacterial species, including those that
      are the most common bacterial pathogens in people (Escherichia coli and
      Staphylococcus aureus). Serious infections caused by resistant bacteria do not
      respond well to therapy and these infections are often associated with worse
      outcomes, including increased rates of complications, additional expense, higher
      associated mortality rates and prolonged hospital stays.

PMID- 22849278
TI  - Clinical impact of antimicrobial resistance in animals.
AB  - It is almost impossible to imagine veterinary medicine today without the use of
      antimicrobials. Shortly after their discovery, antimicrobials found their way
      into the veterinary world. They have brought many benefits for the health and
      welfare of both animals and people, such as the lessening of pain and suffering,
      reduction in shedding of (zoonotic) bacteria and the containment of potentially
      large-scale epidemics. Indirectly, they also contribute to food security,
      protection of livelihoods and animal resources, and poverty alleviation. Given
      the broad range of animal species under veterinary care and the enormous variety
      of infectious agents, a complete range of antimicrobials is needed in veterinary
      medicine. Losing products, either through the occurrence of resistance or through
      a prohibition on their use, will have serious consequences for the health and
      welfare of all animals. It will also seriously affect people who depend on these
      animals. It is a great challenge to everyone involved to stop the growing trend
      of antimicrobial resistance and to safeguard the effectiveness of antimicrobials
      for the future. Transparent and responsible use of antimicrobials, together with
      continuous monitoring and surveillance of the occurrence of resistance, are key
      elements of any strategy. The current situation also urges us to re-think
      unsustainable practices and to work on the development of alternatives, in the
      interests of the health and welfare of both animals and people.

PMID- 22849279
TI  - Evidence for the circulation of antimicrobial-resistant strains and genes in
      nature and especially between humans and animals.
AB  - The concern over antibiotic-resistant bacteria producing human infections that
      are difficult to treat has led to a proliferation of studies in recent years
      investigating resistance in livestock, food products, the environment and people,
      as well as in the mechanisms of transfer of the genetic elements of resistance
      between bacteria, and the routes, or risk pathways, by which the spread of
      resistance might occur. The possibility of transfer of resistant genetic elements
      between bacteria in mixed populations adds many additional and complex potential
      routes of spread. There is now considerable evidence that transfer of
      antimicrobial resistance from food-producing animals to humans directly via the
      food chain is a likely route of spread. The application of animal wastes to
      farmland and subsequent leaching into watercourses has also been shown to lead to
      many potential, but less well-documented, pathways for spread. Often, however,
      where contamination of water sources, processed foods, and other environmental
      sites is concerned, specific routes of circulation are unclear and may well
      involve human sources of contamination. Examination of water sources in
      particular may be difficult due to dilution and their natural flow. Also, as meat
      is comparatively easy to examine, and is frequently suspected of being a source
      of spread, there is some bias in favour of studying this vehicle. Such
      complexities mean that, with the evidence currently available, it is not possible
      to prioritise the importance of potential risk pathways and circulation routes.

PMID- 22849280
TI  - The transfer of antibiotic resistance from food to humans: facts, implications
      and future directions.
AB  - The food chain, from production to the consumer's kitchen, can be an important
      contributor to the development, persistence and dissemination of antibiotic
      resistant (ART) microbes, including both ART foodborne pathogens and commensal
      bacteria. Many factors in the food chain, such as the antimicrobial compounds
      used and how they were used, microbial co-selection, fitness and persistence
      mechanisms, host lifestyle, and food treatment conditions, influence the
      antibiotic resistance (AR) cycle. Targeted mitigation strategies, such as those
      used in the dairy processing industry, can be effective in reducing the AR gene
      pool.

PMID- 22849281
TI  - Quantitative human health risk assessments of antimicrobial use in animals and
      selection of resistance: a review of publicly available reports.
AB  - Quantitative risk assessments have been conducted to estimate the probability and
      magnitude of adverse human health effects from antimicrobial use in food animals
      through selection for antimicrobial resistance in bacteria. The majority focused
      on licensed antimicrobials under regulatory scrutiny, including growth promoters
      and agents of critical importance to human health. Most used models to attribute
      fractions of surveillance-derived estimates of antimicrobial-resistant infections
      in humans to antimicrobial use in animals. Risk estimates ranged from a few
      additional illnesses per million at risk, to many thousands. Although useful,
      published quantitative risk assessments have been unable to comprehensively
      address important aspects of antimicrobial resistance, including multiple
      exposure pathways, interrelationships among bacteria, co-selection, and
      cumulative effects of antimicrobial use in multiple species and countries.
      However, quantitative risk assessment shows promise for synthesis and analysis of
      scientific data. Work is required to develop methodology and train more risk
      analysts. An international forum is needed to pool expertise, review existing
      risk assessments and disseminate the results to risk managers throughout the
      world.

PMID- 22849282
TI  - Containment of antimicrobial resistance due to use of antimicrobial agents in
      animals intended for food: WHO perspective.
AB  - The use of antimicrobial agents in humans and food-producing animals has
      important consequences for human and animal health, as it can lead to the
      development of resistant bacteria (pathogens and/or commensals with resistance
      genes). Moreover, resistant bacteria in animals can be transferred to people-
      usually through the consumption of food, but also through direct contact with
      food-producing animals or through environmental spread. Ultimately, this can
      result in human infections with bacteria that are resistant to antimicrobial
      agents and that can therefore be difficult or impossible to cure. Of special
      concern is resistance to antimicrobial agents classified by the World Health
      Organization (WHO) as critically important for human medicine, such as
      fluoroquinolones, third- and fourth-generation cephalosporins, and macrolides.
      WHO encourages the agricultural, food, veterinary and health sectors to work
      together to eliminate the burden of antimicrobial resistance arising from the use
      of antimicrobial agents in food-producing animals. Joint efforts should be made
      to reduce the inappropriate use of antimicrobial agents (e.g. the use of
      antimicrobials as growth promoters) and limit the spread of bacteria resistant to
      antimicrobial agents. WHO will continueto address this issue in conjunction with
      the Food and Agriculture Organization of the United Nations, the World
      Organisation for Animal Health, the animal health/production industry and other
      important stakeholders. It will also continue to enhance the capacity of its
      Member States (through training courses and sentinel studies), particularly
      developing countries, to conduct integrated surveillance of antimicrobial use and
      resistance, to carry out risk assessments to support the selection of risk
      management options and to implement strategies for the containment of
      antimicrobial resistance.

PMID- 22849283
TI  - Responsibilities of regulatory agencies in the marketing of antimicrobials.
AB  - The regulatory agencies' main responsibility regarding the marketing of
      veterinary medicinal products is to ensure that the products have a marketing
      authorisation with specific conditions of use adequate to ensure the quality,
      safety and efficacy of the product under consideration. In addition, control and
      surveillance systems are necessary to allow monitoring of the product after it
      has been authorised. In respectto antimicrobials, specific consideration must be
      given to minimising resistance development and retaining the effectiveness of
      these drugs for the treatment of humans and animals. Surveillance programmes
      should be in place to follow trends in resistance development, as well as in the
      consumption of veterinary antimicrobials, in order to provide for science-based
      policy recommendations regarding public and animal health.

PMID- 22849284
TI  - Antimicrobial resistance and the guidelines of the International Cooperation on
      Harmonisation of Technical Requirements for Registration of Veterinary Medicinal
      Products (VICH).
AB  - The International Cooperation on Harmonisation of Technical Requirements for
      Registration of Veterinary Medicinal Products (VICH) is an international
      tripartite cooperation programme that brings together regulatory authorities and
      industry representatives from the European Union, Japan and the United States,
      with Australia, New Zealand and Canada as observers. VICH aims to improve
      international coordination and cooperation to achieve greater harmonisation of
      the requirements for veterinary product registration in the regions concerned.
      VICH develops harmonised data requirements, i.e., standards for the scientific
      studies on quality, safety and efficacy that are required to obtain a marketing
      authorisation for a veterinary medicinal product. It does this by publishing
      guidelines that provide uniform and consistent guidance for sponsors to follow in
      developing data for application dossiers as well as for post-marketing safety
      monitoring of veterinary medicinal products. Of the 49 VICH guidelines that have
      been developed so far, two guidelines in particular address issues related to
      antimicrobial resistance.

PMID- 22849285
TI  - Impact assessment of risk management interventions.
AB  - Much effort has been invested in the development and implementation of
      international recommendations to manage the risk of foodborne antimicrobial
      resistance, and monitoring programmes to measure bacterial antimicrobial
      resistance and antimicrobial product volumes. A variety of approaches have been
      recommended for various stakeholders in the food animal and food production
      sectors. Interestingly, much less consideration has been given to the
      establishment of success criteria for the individual interventions and even less
      for the cumulative effects, when all interventions are considered together as
      consecutive 'hurdles' along the food chain. The author explores the outcome and
      unforeseen consequences of these various interventions and appropriate methods
      that could provide data to assess their impact, as well as key learning
      experiences that should lead to refinements of such interventions in the future.

PMID- 22849286
TI  - Antimicrobial resistance and the activities of the Codex Alimentarius Commission.
AB  - The Codex Alimentarius Commission has been working on the subject of
      antimicrobial resistance, mainly through the activities of the Committee on
      Residues of Veterinary Drugs in Foods and the ad hoc Intergovernmental Task Force
      on Antimicrobial Resistance. Principal texts developed by Codex include the 'Code
      of Practice to Minimize and Contain Antimicrobial Resistance (CAC/RCP 61-2005)
      and 'Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance' (CAC/GL
      77-2011). The successful containment of antimicrobial resistance requires the
      collaboration of a wide range of stakeholders, working together to protect
      consumer health by ensuring the safety of food products of animal origin.

PMID- 22849287
TI  - Antimicrobial resistance and the standards of the World Organisation for Animal
      Health.
AB  - Antimicrobial resistance and the use of antimicrobial agents in veterinary
      medicine are complex issues that are currently a source of major international
      concern. It is therefore essential for the World Organisation for Animal Health
      (OIE) to consider this issue, while at the same time continuing to address the
      problem of zoonotic diseases. That is why the OIE has included objectives for
      veterinary drugs, especially antimicrobials, in its Strategic Plan. The OIE plays
      an active part in discussions on this subject in conjunction with other
      international organisations working in this field, such as the Food and
      Agriculture Organization of the United Nations (FAO) and the World Health
      Organization (WHO). Furthermore, the OIE has adopted guidelines both for defining
      harmonised methodologies for antimicrobial resistance surveillance and monitoring
      and for helping countries to conduct a risk analysis tailored to their situation
      and to take appropriate management measures. The OIE has included this issue in
      its programme of assistance to countries by offering them structural enhancement
      tools: the Tool for the Evaluation of Performance of Veterinary Services (O1E PVS
      Tool), PVS Gap Analysis, veterinary legislation support, and training for
      veterinary national focal points, with the aid of its Collaborating Centres for
      veterinary medicinal products. Only by mobilising all countries to improve the
      quality of antimicrobials, to introduce antimicrobial resistance surveillance and
      to implement measures for the responsible and prudent use of antimicrobials, will
      it be possible to halt the spread of antimicrobial resistance.

PMID- 22849288
TI  - Prudent use guidelines: a review of existing veterinary guidelines.
AB  - The World Organisation for Animal Health (OIE) TerrestrialAnimal Health Code
      considers the prudent use of antimicrobial agents in veterinary medicine to
      comprise a series of practical measures and recommendations which confer benefits
      to animal and public health while preserving and maintaining the therapeutic
      efficacy of antimicrobials. This paper reviews some of the main veterinary
      prudent use guidelines which have been published in English and the
      responsibilities of those involved at all levels in the administration of
      antimicrobials to animals, including national regulatory authorities. The OIE
      guidelines are considered comprehensive and cover all of those levels, from
      regulatory authorities to veterinarians and food producers. Guidelines produced
      by national authorities, professional veterinary associations or farming
      associations and which are targeted at particular individuals, for example
      veterinarians or food animal producers, will, obviously, restrict their coverage
      to those aspects considered relevant for their target audience.

PMID- 22849289
TI  - Robot-assisted reconstructive surgery for ureteral malignancy: analysis of
      efficacy and oncologic outcomes.
AB  - BACKGROUND AND PURPOSE: There have been previous reports of the use of robotic
      technology for the surgical treatment of ureteral neoplasms such as transitional
      cell carcinoma. These have lacked long-term follow-up, been isolated cases, or
      focused on only the distal ureter. This investigation examines a series of mid
      and distal ureteral neoplasms managed with surgeon controlled robotic techniques
      at a tertiary care medical center. We present perioperative data and long-term
      follow-up, with emphasis on oncologic outcomes. PATIENTS AND METHODS: This series
      includes six consecutive patients who have undergone robot-assisted surgical
      extirpation of mid and distal ureteral malignancies since 2008. Four patients
      underwent robot-assisted distal ureterectomy with ureteroneocystostomy, and two
      underwent midureter segmental excision with ureteroureterostomy. Patient
      demographics, intraoperative data, final pathology results, and oncologic follow
      up were reviewed retrospectively. RESULTS: Total mean operative time was 268.5
      minutes, including the cystoscopy and change of position component of the
      procedure; mean estimated blood loss was 72.5 mL, and the mean length of stay was
      1.8 days. All four patients who underwent distal ureterectomy also had excisions
      of the ipsilateral bladder cuff-three needed a psoas hitch to facilitate the
      ureteroneocystostomy. Final pathology results revealed four cases of transitional
      cell carcinoma, one case of ureteral carcinoma in situ, and one case of non
      Hodgkin diffuse-type B-cell lymphoma. The only complication was a small hydrocele
      in one patient. All patients underwent standard surveillance protocol, with a
      recurrence in the bladder developing in one patient. Ureteral obstruction did not
      develop in any patient postoperatively. Mean length of follow-up was 33 months.
      CONCLUSIONS: Robot-assisted surgery is well suited for the complex reconstruction
      of the mid and distal ureter after excision of low-grade malignant lesions. This
      series demonstrates that this surgical approach offers excellent intermediate
      term oncologic outcomes with preservation of ipsilateral renal function. We
      believe that robotic surgery may be considered as a first-line option for the
      minimally invasive excision and reconstruction of low-grade, localized ureteral
      malignancy in selected patients at centers with experienced teams.

PMID- 22849290
TI  - Single molecule tracking studies of flow-aligned mesoporous silica monoliths:
      aging-time dependence of pore order.
AB  - Single molecule tracking (SMT) methods are employed to characterize the in-plane
      alignment and order of cylindrical mesopores in flow-aligned surfactant-templated
      silica monoliths prepared within glass microfluidic channels. The majority of dye
      molecules observed in wide-field fluorescence videos of these samples exhibit one
      dimensional (1D) diffusive motions. Orthogonal regression analysis of these
      motions provides a measure of the mesopore orientation distribution function,
      which in turn is used to quantify the mesopore order via a two-dimensional
      orientational order parameter, <P>. Mesopore organization is explored as a
      function of aging time between sol preparation and filling of the microfluidic
      channels. Channels filled well before gelation of the sol are shown to
      incorporate large monodomains having average pore alignment within a few degrees
      of the flow direction. These monodomains extend over several millimeters and
      yield aging-time-independent <P> values larger than ~0.80. In contrast, channels
      filled near the time of sol gelation yield monoliths with misaligned pores that
      are also more disordered, having <P> ~ 0.35. The SMT results are compared to
      those from small-angle X-ray scattering anisotropy experiments; these data are
      consistent across the range of samples investigated. A model describing the aging
      time dependence of sol organization is presented. These studies demonstrate that
      well-aligned mesoporous silica monoliths can be obtained by simple flow alignment
      procedures but that short sol aging times are required in order to achieve
      optimum pore organization.

PMID- 22849292
TI  - Copper(I)-catalyzed amination of aryl halides in liquid ammonia.
AB  - The amination of aryl halides in liquid ammonia (LNH(3)) is catalyzed by a
      copper(I) salt/ascorbate system to yield primary aromatic amines in good to
      excellent yields. The low concentrations of catalyst required and the ease of
      product isolation suggest that this process has potential industrial
      applications. Commonly used ligands for analogous metal-catalyzed reactions are
      not effective. The rate of amination of iodobenzene in liquid ammonia is first
      order in copper(I) catalyst concentration. The small Hammett rho = 0.49 for the
      amination of 4-substituted iodobenzenes in liquid ammonia at 25  degrees C
      indicates that the C-I bond is not significantly broken in the transition state
      structure and that there is a small generation of negative charge in the aryl
      ring, which is compatible with the oxidative addition of the copper ion being
      rate limiting.

PMID- 22849291
TI  - Ultrasound enhanced matrix metalloproteinase-9 triggered release of contents from
      echogenic liposomes.
AB  - The extracellular enzyme matrix metalloproteinase-9 (MMP-9) is overexpressed in
      atherosclerotic plaques and in metastatic cancers. The enzyme is responsible for
      rupture of the plaques and for the invasion and metastasis of a large number of
      cancers. The ability of ultrasonic excitation to induce thermal and mechanical
      effects has been used to release drugs from different carriers. However, the
      majority of these studies were performed with low frequency ultrasound (LFUS) at
      kilohertz frequencies. Clinical usage of LFUS excitations will be limited due to
      harmful biological effects. Herein, we report our results on the release of
      encapsulated contents from substrate lipopeptide incorporated echogenic liposomes
      triggered by recombinant human MMP-9. The contents release was further enhanced
      by the application of diagnostic frequency (3 MHz) ultrasound. The echogenic
      liposomes were successfully imaged employing a medical ultrasound transducer (4
      15 MHz). The conditioned cell culture media from cancer cells (secreting MMP-9)
      released the encapsulated dye from the liposomes (30-50%), and this release is
      also increased (50-80%) by applying diagnostic frequency ultrasound (3 MHz) for 3
      min. With further developments, these liposomes have the potential to serve as
      multimodal carriers for triggered release and simultaneous ultrasound imaging.

PMID- 22849293
TI  - Epigallocatechin-3-gallate modulates antioxidant and DNA repair-related proteins
      in exocrine glands of a primary Sjogren's syndrome mouse model prior to disease
      onset.
AB  - The autoimmune disorder primary Sjogren's syndrome (SS) is associated with
      xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic
      and environmental factors. A major potential contributor is oxidative stress
      associated with damage to cellular components, including DNA. We reported
      previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG)
      normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a
      key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes.
      The current study examined levels of the antioxidant enzymes peroxiredoxin 6
      (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn
      H2 mice, a model for primary SS, and determined the effect of EGCG on their
      expression. PCNA elevation was detected in the submandibular gland and pancreas
      by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior
      to overt onset of symptoms. This early PCNA elevation was followed by a decline
      of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of
      PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar
      patterns were observed in the pancreas, even though these mice do not develop
      diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular
      dysfunction associated with SS-like autoimmune disease, accompanied subsequently
      by decreased PRDX6 antioxidant enzyme levels that could further contribute to
      oxidative stress, and these changes precede inflammatory cell infiltration.
      Importantly, EGCG consumption normalizes the expression of these biomarkers in
      this model. These observations could lead to early diagnosis and intervention of
      autoimmune disorders.

PMID- 22849294
TI  - Transient sulcal hyperintensities on fluid-attenuated inversion recovery in
      migraine with aura: transient sulcal hyperintensities in migraine.
AB  - Migraine has been found to be associated with patent foramen ovale. However, in
      practice, it is difficult to show that microemboli via patent foramen ovale can
      induce a migraine attack. Our patient showed transient sulcal hyperintensities on
      fluid-attenuated inversion recovery images during a migraine attack. This
      supports the hypothesis that microemboli via right-to-left shunt may induce
      migraine attacks through transient occlusion of microcirculation.

PMID- 22849296
TI  - Effect of microparticulated wheat bran on the physical properties of bread.
AB  - Wheat bran and flour mixtures were used in a bread formulation to improve its
      quality characteristics. Wheat bran was microparticulated using a jet mill, and
      this microparticulated wheat bran (MWB) was substituted for a portion of wheat
      flour. As the MWB content increased, water-holding capacity, hardness and
      springiness increased while the swelling property decreased slightly. The
      hardness of bread containing MWB was lower than that made with commercial whole
      wheat flour (WWF). Bread containing 7% MWB had a higher specific volume (8.3%)
      than that of WWF bread. Enthalpy of dough decreased with increasing MWB content,
      and peak viscosity and breakdown decreased with increasing setback. Inner crust
      structures of bread containing MWB showed a slight reduction in gelatinization
      and gluten development in comparison with wheat bread. These results indicate
      that MWB could be used as a diet-enriching bread ingredient while maintaining
      bread quality.

PMID- 22849295
TI  - Folate status of gut microbiome affects Caenorhabditis elegans lifespan.
AB  - In a paper in BMC Biology Virk et al. show that Caenorhabditis elegans lifespan
      is extended in response to a diet of folate-deficient Escherichia coli. The
      deficiencies in folate biosynthesis were due to an aroD mutation, or treatment of
      E. coli with sulfa drugs, which are mimics of the folate precursor para
      aminobenzoic acid. This study suggests that pharmacological manipulation of the
      gut microbiome folate status may be a viable approach to slow animal aging, and
      raises questions about folate supplementation.

PMID- 22849297
TI  - Expression and characterization of recombinant interleukin-21 receptor and its
      targeting single-chain variable fragment antibodies selected from a human phage
      display library.
AB  - Interleukin-21 receptor (IL-21R) is widely expressed in lymphocytes, and plays an
      important role in immunological cell proliferation and cytokine production. The
      present study aims to express a recombinant extracellular domain of human IL-21R
      (rhIL-21R-ECD) with high yield, and to screen the anti-IL-21R single-chain
      variable fragments (scFvs) from a synthetic human phage display library. The rhIL
      21R-ECD, being expressed mainly as insoluble inclusion bodies in Escherichia coli
      BL21 (DE3), was purified and refolded. ELISA analysis showed that the refolded
      rhIL-21R-ECD bound to its ligand IL-21 in a concentration-dependent manner. Using
      a phage display technique, anti-IL-21R scFvs were screened from a naive human
      phage display library by biopanning. After four rounds of panning, positive
      clones were isolated, sequenced, and characterized. The clone with highest
      activity was designated as C2. Flow cytometry analysis showed that the scFv C2
      could recognize IL-21R on Jurkat cells. Furthermore, proliferation assay revealed
      a concentration-dependent inhibitory effect of C2 on the Jurkat cell, with fifty
      percent inhibitory concentration (IC(50)) of 78 nM. A human scFv antibody C2 with
      a high binding specificity to IL-21R was isolated and characterized. The antibody
      showed a concentration-dependent inhibitory effect on Jurkat cell proliferation.

PMID- 22849298
TI  - Estimating ancestry and heterozygosity of hybrids using molecular markers.
AB  - BACKGROUND: Hybridization, genetic mixture of distinct populations, gives rise to
      myriad recombinant genotypes. Characterizing the genomic composition of hybrids
      is critical for studies of hybrid zone dynamics, inheritance of traits, and
      consequences of hybridization for evolution and conservation. Hybrid genomes are
      often summarized either by an estimate of the proportion of alleles coming from
      each ancestral population or classification into discrete categories like F1, F2,
      backcross, or merely "hybrid" vs. "pure". In most cases, it is not realistic to
      classify individuals into the restricted set of classes produced in the first two
      generations of admixture. However, the continuous ancestry index misses an
      important dimension of the genotype. Joint consideration of ancestry together
      with interclass heterozygosity (proportion of loci with alleles from both
      ancestral populations) captures all of the information in the discrete
      classification without the unrealistic assumption that only two generations of
      admixture have transpired. METHODS: I describe a maximum likelihood method for
      joint estimation of ancestry and interclass heterozygosity. I present two worked
      examples illustrating the value of the approach for describing variation among
      hybrid populations and evaluating the validity of the assumption underlying
      discrete classification. RESULTS: Naively classifying natural hybrids into the
      standard six line cross categories can be misleading, and false classification
      can be a serious problem for datasets with few molecular markers. My analysis
      underscores previous work showing that many (50 or more) ancestry informative
      markers are needed to avoid erroneous classification. CONCLUSION: Although
      classification of hybrids might often be misleading, valuable inferences can be
      obtained by focusing directly on distributions of ancestry and heterozygosity.
      Estimating and visualizing the joint distribution of ancestry and interclass
      heterozygosity is an effective way to compare the genetic structure of hybrid
      populations and these estimates can be used in classic quantitative genetic
      methods for assessing additive, dominant, and epistatic genetic effects on hybrid
      phenotypes and fitness. The methods are implemented in a freely available package
      "HIest" for the R statistical software ( http://cran.r
      project.org/web/packages/HIest/index.html).

PMID- 22849300
TI  - Sedative load and functional outcomes in community-dwelling older Australian men:
      the CHAMP study.
AB  - The aim of this cross-sectional study was to investigate the association between
      sedative load and functional outcomes in community-dwelling older Australian men.
      A total of 1696 males aged >= 70 years, enrolled in the Concord Health and Ageing
      in Men Project, were studied. Participants underwent assessments during 2005
      2007. Sedative load was computed using a published model. Outcomes included
      activities of daily living (ADL), instrumental activities of daily living (IADL),
      physical performance measures and a clinical diagnosis of cognitive impairment.
      Of the participants, 15.3% took medications with sedative properties. After
      adjusting for age, education, depressive symptoms and comorbidities, participants
      who took one medication with sedation as a prominent side effect (sedative load =
      1) had odds ratio (OR) of 2.15 (95% confidence interval, CI: 1.20-3.85) for ADL
      disability, compared with participants with sedative load = 0. Participants who
      took at least one primary sedative or two medications with sedation as a
      prominent side effect (sedative load >= 2) had an OR of 1.55 (95% CI: 1.02-2.35)
      for IADL disability, compared with participants with sedative load = 0. The mean
      6-m walking speed (P = 0.001) and grip strength (P = 0.003) were significantly
      different between sedative load groups in unadjusted models only. No association
      between sedative load and poorer performance on balance and chair stands tests or
      cognitive impairment was observed. Participants with sedative load of one were
      more likely to report ADL disability, whereas participants with sedative load of
      >=2 were more likely to report IADL disability. Higher sedative load was not
      associated with poorer physical performance or cognitive impairment in older
      Australian men.

PMID- 22849299
TI  - Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E
      deficient mice.
AB  - BACKGROUND: Stem/progenitor cell-based therapy has successfully been used as a
      novel therapeutic strategy for vascular diseases triggered by endothelial
      dysfunction. The aim of this study was to investigate the effects of mononuclear
      cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the
      apolipoprotein E knockout (apoE-/-) mouse. METHODS: Spleen-derived MNCs were
      isolated from green fluorescent protein (GFP)-transgenic mice for cell treatment.
      A cuff-induced thrombus model was produced by placing a nonconstrictive silastic
      collar around the left common carotid artery in 20-week-old female apoE-/- mice.
      After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff
      MNC) or vehicle (Cuff-Vehicle) and were compared with sham-operated animals
      (Sham). RESULTS: The histological analysis showed that the MNC treatment reverted
      occlusive thrombus formation compared to the vehicle and the vessel lumen area to
      that observed in the Sham group (MNC, 50 +/- 4; Vehicle, 20 +/- 4; Sham, 55 +/- 2
      x103 MUm2; p < 0.01). The animals that underwent the carotid cuff placement
      developed compensatory vessel enlargement, which was reduced by the MNC therapy.
      In addition, the treatment was able to reduce superoxide anion production, which
      likely contributed to the reduced apoptosis that was observed. Lastly, the
      immunofluorescence analysis revealed the presence of endothelial progenitor cells
      (EPCs) in the carotid endothelia of the apoE-/- mice. CONCLUSION: In situ short
      term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid
      arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of
      oxidative stress and decreased apoptosis.

PMID- 22849301
TI  - Muscle- and task-dependent responses to concurrent physical and mental workload
      during intermittent static work.
AB  - Many workers experience combined physical and mental demands in their jobs, yet
      the contribution of these demands to the development of musculoskeletal disorders
      is unclear. The purpose of this study was to investigate muscle- and task
      dependent responses to concurrent demands during intermittent static work. Twenty
      four participants performed shoulder, wrist, and torso exertions at three levels
      of physical workload (PWL) in the absence (control) and presence (concurrent) of
      a mental arithmetic task. Compared to the control, concurrent demand conditions
      resulted in decreased muscle activity (4-9% decrease), increased cardiovascular
      load (2-4% increase), and impaired motor co-ordination (9-24% increase in force
      fluctuation). Furthermore, these outcomes were more prominent at higher PWL
      levels and within postural (shoulder and torso) muscles. Mental task performance
      exhibited greater interference with the physical task at low and high PWL levels.
      Thus, it may be important to consider these muscle- and task-specific
      interactions of concurrent demands during job design to address worker health and
      performance issues. PRACTITIONER SUMMARY: Occupational tasks place both physical
      and mental demands on workers. These demands can adversely affect physiological
      responses and performance, and are muscle- and task-dependent. Findings from this
      research may facilitate the development of ergonomics interventions, such as task
      redesign and tool/workstation design, that may help reduce risk of workplace
      injuries.

PMID- 22849302
TI  - Oxidative alkenylation of aromatic esters by ruthenium-catalyzed twofold C-H bond
      cleavages.
AB  - Cationic ruthenium(II) complexes enabled catalytic twofold C-H bond
      functionalizations with weakly coordinating aromatic esters in a highly chemo-,
      site- and diastereo-selective as well as site selective fashion. The oxidative
      Fujiwara-Moritani-type alkenylation provided step-economical access to diversely
      substituted styrenes and proved viable in an aerobic manner. Mechanistic studies
      were indicative of a reversible acetate-assisted cycloruthenation step.

PMID- 22849303
TI  - Control of regioselectivity and stereoselectivity in (4 + 3) cycloadditions of
      chiral oxyallyls with unsymmetrically disubstituted furans.
AB  - The regioselectivities and stereoselectivities of ZnCl2-catalyzed (4 + 3)
      cycloadditions between chiral oxazolidinone-substituted oxyallyls and
      unsymmetrical disubstituted furans have been determined. The substitution pattern
      on the furan is found to provide a valuable tool for controlling the
      stereochemistry (endo-I or endo-II) of the 7-membered cycloadduct. While
      cycloadditions with monosubstituted furans usually favor endo-I products, from
      addition of the furan to the more crowded face of the oxyallyl, cycloadditions
      with 2,3- and 2,5-disubstituted furans instead favor the endo-II stereochemistry.
      Density functional theory calculations are performed to account for the
      selectivities. For monosubstituted furans, the crowded transition state leading
      to the endo-I cycloadduct is stabilized by an edge-to-face interaction between
      the furan and the oxazolidinone 4-Ph group, but this stabilization is overcome by
      steric clashing if the furan bears a 2-CO2R group or is 2,3-disubstituted.

PMID- 22849304
TI  - Lesions of hypothalamic mammillary body desynchronise milk-ejection bursts of rat
      bilateral supraoptic oxytocin neurones.
AB  - Successful milk ejection depends on a bolus release of oxytocin, which results
      from the synchronised burst firing of magnocellular oxytocin neurones in several
      hypothalamic nuclei. Despite extensive studies of the mechanism underlying the
      burst synchrony of oxytocin neurones in the same nucleus, brain regions
      controlling burst synchronisation among different nuclei remain elusive. We
      hypothesised that some structures in the ventroposterior hypothalamus may
      function as the major component of neural circuits controlling burst
      synchronisation of bilateral oxytocin neurones. To test this hypothesis, we
      recorded burst firing of bilateral oxytocin neurones in the two supraoptic nuclei
      after microsurgical disconnection of different hypothalamic regions in
      anaesthetised lactating rats. The results obtained showed that the
      interhemispheric section of the caudal part of the hypothalamus but not the
      rostral hypothalamus resulted in burst desynchronisation. The difference in burst
      onset time between paired bursts of bilateral oxytocin neurones was 129.2 +/-
      34.7 s, which is significantly (P < 0.01) longer than that of sham-lesioned
      controls (0.24 +/- 0.02 s). Hypothalamic lesions leading to the desynchronisation
      involved the mammillary body, supramammillary nucleus and tuberomammillary
      nucleus in the ventroposterior hypothalamus. Consistently, electrolytic lesion of
      the median part of this mammillary body region also desynchronised the burst of
      bilateral oxytocin neurones and disrupted milk ejections. These results indicate
      that the mammillary body region is critically involved in the burst
      synchronisation of bilateral oxytocin neurones during suckling and possibly
      functions as the major component of a putative synchronisation centre.

PMID- 22849305
TI  - Induction of microRNA-214-5p in human and rodent liver fibrosis.
AB  - BACKGROUND: miRNAs are non-coding RNAs that regulate gene expression in a wide
      range of biological contexts, including a variety of diseases. The present study
      clarified the role of miR-214-5p in hepatic fibrogenesis using human clinical
      tissue samples, livers from rodent models, and cultured hepatic stellate cells.
      METHODS: The expression of miR-214-5p and genes that are involved in liver
      fibrosis were analyzed in hepatitis C virus-infected human livers, rodent
      fibrotic livers, a human stellate cell line (LX-2), and the cells from intact
      mouse livers using real-time PCR. The effect of miR-214-5p overexpression in LX-2
      cells on cell function was investigated. Twist-1 expression in the liver tissues
      of mouse models and primary-cultured stellate cells was also analyzed. RESULTS:
      miR-214-5p was upregulated in human and mouse livers in a fibrosis progression
      dependent manner. miR-214-5p expression increased during the culture-dependent
      activation of mouse primary stellate cells and was significantly higher in
      stellate cells than in hepatocytes. The overexpression of miR-214-5p in LX-2
      cells increased the expression of fibrosis-related genes, such as matrix
      metalloproteinase (MMP)-2, MMP-9, alpha-smooth muscle actin, and transforming
      growth factor (TGF)-beta1. TGF-beta stimulation induced miR-214-5p in LX-2 cells.
      Twist-1 was increased in fibrotic mouse livers and induced during mouse stellate
      cell activation. CONCLUSION: miR-214-5p may play crucial roles in the activation
      of stellate cells and the progression of liver fibrosis. Twist-1 may regulate miR
      214-5p expression in the liver, particularly in stellate cells.

PMID- 22849306
TI  - Prevalence of disturbed bowel functions and its association with disturbed
      bladder and sexual functions in the male population.
AB  - BACKGROUND AND AIM: Chronic constipation is usually associated with young women,
      and urinary and sexual dysfunction has been reported as co-morbidity. Elderly men
      also appear to suffer from chronic constipation, as well as lower urinary tract
      symptoms and erectile dysfunction, but their association as co-morbidity has not
      been studied in the community. The aim of the present study was to determine the
      prevalence of bowel symptoms in our community with particular reference to the
      association with urinary and sexual dysfunction in the male population. METHODS:
      A population-based cross-sectional survey involving 2276 subjects (1143 male,
      1133 female) representative of the Singapore population demographics was
      conducted to evaluate the prevalence of chronic bowel disturbances, lower urinary
      tract symptoms (LUTS), and erectile dysfunction (ED). RESULTS: The prevalence of
      chronic constipation was 25.1% overall, with the highest in men aged >= 70 years
      (35.8%) followed by women aged 20-29 years (30.5%). The commonest symptoms
      reported in chronic constipation were hard stool (95.1%), straining (90.9%) and
      incomplete evacuation (53.8%). Bloating was often experienced by 25.5% of the
      community, among whom 61.1% had some form of bowel disturbance. In men aged >= 30
      years, LUTS (7.8% v 3.1%) and ED (60.5% v 48.6%) were more common in men with
      than without chronic constipation; constipation was an independent predictor of
      ED. CONCLUSIONS: In this Asian urban community, chronic constipation was more
      common than previously suspected, and urinary and erectile dysfunction were found
      to be co-morbidity in men.

PMID- 22849307
TI  - Necrosis is not induced by gadolinium neutron capture in glioblastoma multiforme
      cells.
AB  - PURPOSE: A comparative study of the effects of different radiation modalities on
      cell death was performed. MATERIALS AND METHODS: Radiation modalities included
      gamma-rays, fast neutrons, a mixed energy neutron beam called the modified
      enhanced thermal neutron beam and the mixed beam including Auger electron
      irradiation by gadolinium neutron capture. U87 (human brain tumor cells) cell
      survival curve data were modeled to predict how cells died. Transmission electron
      microscopy (TEM) images were assembled into a morphology of cell death (MCD)
      database and used to determine the fraction of necrotic or autophagic cells.
      RESULTS: Linear energy transfer (LET) differences for the different radiation
      modalities were revealed by modeling. All radiation modalities induced autophagy
      but only fast neutrons induced significant levels of necrosis. No necrosis, above
      control levels, was found in cells irradiated with mixed beam irradiation
      including Auger electrons. The number of autophagosomes increased with increasing
      time after exposure to all radiation modalities indicating progression of
      autophagy but only cells irradiated with the mixed beam plus Auger electrons
      exhibited extreme autophagy. CONCLUSIONS: Mixed neutron beam irradiation plus
      Auger electron irradiation from gadolinium neutron capture is a moderately high
      LET modality that kills U87 cells without the induction of necrosis and with
      progression of autophagy to an extreme state.

PMID- 22849308
TI  - The effect of weight-based volume loading on the inferior vena cava in fasting
      subjects: a prospective randomized double-blinded trial.
AB  - OBJECTIVES: Inferior vena cava ultrasound (IVC-US) assessment has been proposed
      as a noninvasive method of assessing volume status. Current literature is divided
      on its ability to do so. The primary objective was to compare IVC-US changes in
      healthy fasting subjects randomized to either 10 or 30 mL/kg of intravenous (IV)
      fluid administration versus a control group that received only 2 mL/kg. METHODS:
      This was a prospective randomized double-blinded trial set in emergency
      department (ED) clinical care rooms. Volunteer subjects with no history of
      cardiac disease or hypertension fasted for 12 hours. Subjects were randomly
      assigned to receive IV 0.9% saline bolus of 2 (control group), 10, or 30 mL/kg
      over 30 minutes. IVC-US was performed before and 15 minutes after each fluid
      bolus. RESULTS: Forty-two fasting subjects were enrolled. Analysis of variance
      (ANOVA) comparison showed that IVC-US was unable to detect any significant
      difference between the control group and those given either 10 or 30 mL/kg fluid,
      whether using maximum or minimum IVC diameter or caval index (IVC-CI). The groups
      receiving 10 and 30 mL/kg each had a statistically significant change in IVC-CI;
      however, the 30 mL/kg group had no significant change in either of the mean IVC
      diameters. CONCLUSIONS: Overall, there were statistically significant differences
      in mean IVC-US measurements before and after fluid loading, but not between
      groups. Fasting asymptomatic subjects had a wide intersubject variation in both
      baseline IVC-US measurements and fluid-related changes. The degree of IVC-US
      change in association with graded acute volume loading was not predictably
      proportional between our subjects.

PMID- 22849309
TI  - Infection rate of Eperythrozoon spp. in Chinese population: a systematic review
      and meta-analysis since the first Chinese case reported in 1991.
AB  - BACKGROUND: Eperythrozoonosis is an important animal health problem worldwide, it
      not only has a major impact on the economic viability, but also makes a
      significant impact on public health issues. The present systemic review intends
      to collate all relevant published data to assess the burden of Eperythrozoon
      infection in Chinese population and discuss the implications of these findings
      for public health policy. METHODS: A meta-analysis was conducted to review the
      published studies that reported Eperythrozoon spp. in Chinese population.
      Inclusion criteria comprised of the use of microscopic venous blood smear
      examination for Eperythrozoon detection and a detailed description of sampling
      techniques. RESULTS: Twenty-four cross-sectional studies with 52,433 participants
      and 14,951 positive cases, within the range of China mainland, were included in
      the present analysis. The infection rate of Eperythrozoon varied from 0 to 97.29%
      with geographical and seasonal variations, people with mild infection intensity
      contributed the major part (68.93%). The infection rates were highest in the
      children and adolescents group, significantly increased risk of Eperythrozoon
      infection was found among herdsmen. CONCLUSIONS: The current study raises
      awareness about the human eperythrozoonosis in China, which is a newly emerging
      zoonosis. The majority of Eperythrozoon infection intensity was asymptomatic mild
      infection. The infection rate of Eperythrozoon in Chinese population varied by
      geographical region, season, age and occupation. These factors need to be
      considered when conducting health education campaigns and comparing the
      surveillance results from different studies.

PMID- 22849310
TI  - The Devon Active Villages Evaluation (DAVE) trial: study protocol of a stepped
      wedge cluster randomised trial of a community-level physical activity
      intervention in rural southwest England.
AB  - BACKGROUND: Although physical inactivity has been linked with numerous chronic
      health conditions and overall mortality, the majority of English adults report
      doing insufficient physical activity. To increase population physical activity
      levels, researchers have called for more community-level interventions. To
      evaluate these complex public health interventions, innovative study designs are
      required. This study protocol describes Devon Active Villages, a community-level
      intervention providing physical activity opportunities to 128 rural villages in
      southwest England, and the methods used to evaluate its effectiveness in
      increasing physical activity levels. METHODS/DESIGN: A stepped wedge cluster
      randomised trial will be used to evaluate whether Devon Active Villages leads to
      increased physical activity levels in rural communities. Community engagement
      will help tailor activity programmes for each village; communities will then be
      supported for a further twelve months. The intervention will be delivered over
      four periods, each lasting twelve weeks. Data collection consists of a postal
      survey of a random sample of adults aged 18 years and over, at baseline and after
      each of the four intervention periods. The questionnaire includes questions on
      participant demographics, physical activity behaviour, local environment
      characteristics, awareness of local activity programmes, and psychosocial
      factors. Based on detecting an increase in the proportion of people who meet
      physical activity guidelines (from 25% to 30%), at least ten respondents are
      needed from each of the 128 villages at each stage (80% power at the 5% level of
      significance). Anticipating a 20% response rate, 6,400 questionnaires will be
      sent out at each stage (i.e., 50 surveys to each village). Using data from all
      five periods, a comparison of study outcomes between intervention and control
      arms will be performed, allowing for time period (as a fixed effect) and the
      random effect induced by correlation of outcomes (clustering) within villages.
      DISCUSSION: This paper describes the use of a stepped wedge cluster randomised
      trial to evaluate a complex, community-level physical activity intervention in an
      under-studied population of adults in rural communities in southwest England. The
      study addresses gaps in the current literature by providing new insights into
      physical activity levels in this population. TRIAL REGISTRATION NUMBER: Current
      Controlled Trials ISRCTN37321160.

PMID- 22849311
TI  - Green leafy porridges: how good are they in controlling glycaemic response?
AB  - Green leafy porridges made with leaf water extracts, rice and coconut milk are
      common Sri Lankan dietary remedies for diabetes. Though water and ethanolic
      extracts of most leaves elicit hypoglycaemic effects, data are not available on
      the efficacy when leaf extracts are incorporated into porridges. Thus, an effort
      was made to evaluate the proximate compositions and glycaemic index (GI) of some
      commonly consumed green leafy porridges. The GI of rice porridge and coconut milk
      porridge were measured to evaluate the effect of other ingredients other than the
      leaf extracts. Rice was the main contributor to carbohydrate (56-68% on dry
      weight) and water was the main component in porridges (89-93%). Fat and total
      dietary fibre contents ranged between 2.5-27% and 5-10%, respectively. The GI of
      all porridges was low (GI <= 55), except Cassia auriculata which had a high GI of
      77 +/- 12. The GIs of coconut milk, Aerva lanata, Hemidesmus indicus, Scoparia
      dulcis, Asparagus racemosus, Cephalandra indica, Cardiospermum halicacabum,
      Murraya koenigii and Aegle marmelos were 31 +/- 5, 32 +/- 5, 40 +/- 8, 39 +/- 8,
      37 +/- 4, 49 +/- 8, 46 +/- 8, 44 +/- 8 and 50 +/- 8, respectively. All porridges
      had a low or medium glycaemic loads ( <= 19). However, peak blood glucose
      reductions of >= 25% were observed in all leafy and coconut milk porridges,
      except in C. auriculata and Atlantia zeylanica, when compared with the glucose
      control. Therefore, green leafy porridges, except Cassia, can be recommended as
      breakfast meals for diabetics due to their low GI, peak blood glucose reduction
      and presence of other nutrients in green leaves.

PMID- 22849312
TI  - Influence of whole-body vibration on biodistribution of the radiopharmaceutical
      [99mTc]methylene diphosphonate in Wistar rats.
AB  - PURPOSE: The radionuclide bone scan is the basis of skeletal nuclear medicine
      imaging. Bone scintigraphy is a highly sensitive method for indicating disease in
      bone. Mechanical stimulation in the manner of whole-body vibration (WBV) appears
      beneficial to the maintenance and/or enhancement of skeletal mass in individuals.
      The aim of this work was to evaluate the effect of WBV on the biodistribution of
      the radiopharmaceutical [99mTc]methylene diphosphonate (99mTc-MDP) in Wistar
      rats. MATERIALS AND METHODS: In the biodistribution analysis, animals were
      anesthetized with sodium thiopental, the radiopharmaceutical (99m)Tc-MDP was
      administered via ocular plexus and after 10 min the animals were submitted to
      vibration of 20 Hz (1 min) in an oscillatory platform. Following, the animals
      were sacrificed, the organs were isolated, the radioactivity determined in a well
      counter, and the percentages of radioactivity per gram (%ATI/g) in the organs
      were calculated. An unpaired t-test following Welch test (p < 0.05) was done for
      statistical analysis of the results. RESULTS: The biodistribution was
      significantly (p < 0.05) decreased in kidney, bone, lung, stomach, prostate and
      bowel. CONCLUSION: The analysis of the results indicates that the vibration could
      produce metabolic alterations with influence in the uptake of the
      radiopharmaceutical 99mTc-MDP in bone, stomach, bowel, prostate, kidney and
      bladder.

PMID- 22849313
TI  - Injury prevention and safety promotion course in a Russian Master of Public
      Health programme.
AB  - The Global Burden of Disease Studies describe and emphasise injury as a major and
      increasing component in the panorama of global ill health. Russia has the one of
      the highest injury rates in Europe. When a Master in Public Health programme was
      planned and started in 2007 in Arkhangelsk, Russia, under the auspices of
      University of Tromso, Norway, a course on Injury Prevention and Safety Promotion
      was included. A take-over programme (training-the-trainers) was implemented
      within the course. The present paper describes the course content, the students
      and their background, the training-the-trainers programme, the evaluation
      procedure and its results. So far, 53 students have passed the course, 77% being
      female. The majority of students were medical doctors (51%), psychologists (11%),
      pedagogues (9%), dentists (6%) and nurses (6%). The take-over programme has
      functioned well by gradually using students of excellence as teachers. In 2012,
      the take-over programme is completed and only Russians teach. Evaluation by
      students of the course content, organisation and pedagogic approach was useful
      for improvements.

PMID- 22849314
TI  - Keratinocyte growth factor (KGF) delays the onset of collagen-induced arthritis.
AB  - BACKGROUND: Keratinocyte growth factor (KGF) is a member of the fibroblast growth
      factor family. KGF protects the oral and intestinal mucosa against damage induced
      by irradiation or chemotherapy. Previous studies have found the expression of KGF
      in chondrocytes and suggested that KGF promotes the wound healing process in
      injured cartilage. KGF also has important effects on the immune system such as
      the regeneration of thymus tissue and the formation of regulatory T cells
      (T(reg)) in the periphery. AIM: Here we investigated the effect of KGF on
      collagen type II induced arthritis (CIA) and anti-collagen antibody induced
      arthritis (CAIA) in order to discriminate between immunoregulatory effect and
      direct protective effect on chondrocytes. METHODS: CIA was induced by
      immunization with CII and CAIA by treatment of mice with a cocktail of four
      different anti-CII antibodies. The effect of KGF on the thymus and spleen was
      analyzed by FACS and by immunohistochemistry. RESULTS: We have found that KGF
      treatment delayed the onset of CIA but had no effect on CAIA. Our results show
      that KGF treatment leads both to an outflow of naive T cells from the thymus and
      to a statistically significant increase in the percentage of CD4(+)Foxp3(+)
      T(regs) in the periphery. CONCLUSIONS: We suggest that the effect of KGF on CIA
      depends on immunoregulatory mechanisms. KGF may delay the aging of the cellular
      immune system and thus improve the resilience of the immune system against
      autoimmune reactions.

PMID- 22849315
TI  - Safety and efficacy of removable inferior vena cava filters in anticoagulated
      patients undergoing percutaneous nephrostolithotomy.
AB  - BACKGROUND AND PURPOSE: Increasing numbers of patients are receiving a diagnosis
      of thrombophilic conditions necessitating chronic anticoagulation therapy. The
      best management approach for such patients needing percutaneous
      nephrostolithotomy (PCNL) has not been established. Discontinuing anticoagulation
      therapy before PCNL is needed to prevent hemorrhage, placing some of these
      patients at risk for thromboembolic events. We describe the use of removable
      inferior vena cava filters (RIVCF) in patients undergoing PCNL who are at risk
      for a venous thromboembolic event. PATIENTS AND METHODS: A retrospective study of
      outcomes of PCNL with RIVCF placement was conducted. RESULTS: Four patients
      underwent PCNL with RIVCF placement on the same day of the procedure. The mean
      age was 49 years (range 35-69 years). PCNL was performed on a total of six renal
      units with a mean of 2.2 (range 1-3) operations per renal unit. Five of six (83%)
      renal units were rendered stone free. There were no complications associated with
      either the PCNL or RIVCF placement. No patient had a thromboembolic event or
      received blood products. Two of the four patients underwent successful removal of
      the RIVCF, and one elected to keep the device in place. The device could not be
      extracted in the other patient. The average length that the filters were in place
      was 52.5 days. Patients resumed anticoagulation therapy shortly after RIVCF
      removal. CONCLUSION: RIVCF placement is a safe and effective method of preventing
      venous thromboembolic complications in thrombophilic patients needing PCNL.
      Patients should be informed, however, that RIVCF removal is not always possible.

PMID- 22849316
TI  - A biomechanical and subjective assessment and comparison of three ambulance cot
      design configurations.
AB  - Effects of ambulance cot design features (handle design and leg folding
      mechanism) were evaluated. Experienced ambulance workers performed tasks
      simulating loading and unloading a cot to and from an ambulance, and a cot
      raising task. Muscle activity, ratings of perceived exertion, and performance
      style were significantly affected by cot condition (p < 0.05). Erector Spinae
      activity was significantly less when using Cot-2's stretcher-style handles.
      Shoulder muscle activity was significantly less when using Cot-2's loop handle.
      During loading and unloading, operators allowed the cot to support its own weight
      most often with Cot-2's stretcher-style handles. Preference for Cot-2 (either
      handles) over Cot-1 (with loop handle) was consistent across tasks. Handle
      effects were influenced by operator stature; taller participants received more
      benefit from Cot-2's stretcher-style handles; shoulder muscles' demands were
      greater for shorter participants due to handle location. Providing handle options
      and automatic leg folding/unfolding operation can reduce cot operator's effort
      and physical strain.    Practitioner Summary: Paramedics frequently incur
      musculoskeletal injuries associated with patient-handling tasks. A controlled
      experiment was conducted to assess effects of ambulance cot design features on
      physical stress of operators, as seen through muscle activity and operator's
      perceptions. Differences between cots were found, signalling that intentional
      design can reduce operator's physical stress.

PMID- 22849318
TI  - Fatty acid content of serum lipid fractions and blood lipids in normolipidaemic
      volunteers fed two types of cheese having different fat compositions: a pilot
      study.
AB  - The aim of this randomised, double-blind, crossover study in normolipidaemic
      volunteers was to investigate the effect of consumption of an experimental cheese
      (from cows fed a grass and maize silage-based diet with 5% of linseed oil added)
      or a control cheese (without linseed oil) on both plasma lipids and fatty acid
      content of serum lipid fractions. A lower content of medium-chain saturated fatty
      acids as well as a higher content of stearic acid and polyunsaturated fatty acids
      were found in the experimental cheese; its consumption was successful in limiting
      the enhanced blood concentration of atherogenic fatty acids, without affecting
      fatty acid content of serum lipid fractions. These results indicate that dairy
      products could be considered as key foods for fat modifications with the
      objective of optimizing their nutritional quality.

PMID- 22849319
TI  - Evaluation of the Effect of Photoselective Vaporization of the Prostate on Sexual
      Function in a Prospective Study: A Single Center Experience of 150 Patients.
AB  - Abstract   Background and Purpose: Photoselective vaporization of the prostate
      (PVP) has emerged as a minimally invasive alternative to transurethral resection
      of the prostate for treatment of benign prostate hyperplasia (BPH) with lower
      urinary tract symptoms (LUTS). Very few prospective studies have addressed the
      effect of PVP on sexual function. We performed this prospective study to assess
      the short-term effect of PVP on erectile function in patients who present with
      LUTS secondary to BPH.   Patients and Methods: There were 150 consecutive
      patients who presented with LUTS secondary to BPH who underwent PVP and who were
      enrolled prospectively in this study. Patients were categorized in two groups:
      Group A, International Index of Erectile Function (IIEF) >=19; group B, IIEF <19.
      PVP was performed by using an 80 W GreenLight laser. Patients preoperative,
      perioperative, and follow-up data were recorded. Erectile function was assessed
      preoperatively and postoperatively at 1, 3, 6, and 12 months using IIEF-5. In
      follow-up, Ultrasonography of the kidneys, ureters, and bladder for residual
      prostate and postvoid residual urine, uroflowmetry, kidney function tests, and
      urine culture were performed at each visit. Cystoscopy was performed at 3 months.
      Data were analyzed statistically.   Results: The two patient groups were
      comparable in their preoperative and perioperative data. Both groups showed
      improvement in International Prostate Symptom Score, maximum flow rate, quality
      of life, and decrease in postvoid residual urine at 1, 3, 6, and 12 months with
      no statistical significance. IIEF-5 scores in Group A, however, were 21.1, 19.2,
      17.1, 16.2, and 16.1, respectively, at preoperative, postoperative month 1, 3, 6,
      and 12, respectively (P=0.02). IIEF-5 scores in Group B were 13.2, 12.1, 11.3,
      11.2, and 10.9, respectively, at preoperative, postoperative month 1, 3, 6, and
      12, respectively (P=0.45).   Conclusions: In patients with normal preoperative
      erectile function, PVP resulted in significant decrease in EF up to follow-up of
      1 year. In patients with preoperative ED, however, PVP did not significantly
      decrease EF.

PMID- 22849320
TI  - Effects of aircraft cabin noise on passenger comfort.
AB  - The effects of cabin noise on subjective comfort assessments were systematically
      investigated in order to reveal optimisation potentials for an improved passenger
      noise acceptance. Two aircraft simulation studies were conducted. An acoustic
      laboratory test facility provided with loudspeaker systems for realistic sound
      presentations and an aircraft cabin simulator (Dornier Do 728) with a high degree
      of ecological validity were used. Subjects were exposed to nine different noise
      patterns (three noise levels ranging from 66 to 78 dB(A) combined with three
      different frequency spectra). Regression analysis demonstrated a significant
      increase of passengers' acceptance with lower noise levels and significant
      effects of different frequency spectra determined by seat position in the
      aircraft cabin (front, middle, rear). Acoustic cabin design should therefore
      consider measures beyond noise level reduction altering noise characteristics to
      improve passengers' comfort and well-being in the aircraft cabin. PRACTITIONER
      SUMMARY: To improve passenger comfort in the aircraft with respect to cabin
      noise, passengers' reactions to specific noise conditions were systematically
      investigated. Two laboratory studies showed significant dose-response
      relationships between sound pressure level and subjective comfort ratings which
      differed due to the noise at specific seat positions in the aircraft.

PMID- 22849321
TI  - Measuring compliance with Viet Nam's mandatory motorcycle helmet legislation.
AB  - The objective of this roadside observational study was to monitor helmet wearing
      among motorcycle riders and passengers in three provinces (Yen Bai, Da Nang and
      Binh Duong) in the Socialist Republic of Viet Nam, before and after a mandatory
      helmet law took effect on 15 December 2007. A total of 665,428 motorcycle riders
      and passengers were observed between November 2007 and February 2011 at 45
      randomly selected sites covering the entire road network. Across all locations
      and time periods, correct helmet wearing averaged 40.1% before the law and 92.5%
      after; however, there were significant differences between time points and
      locations. The Viet Nam Government's decision to require all motorcycle riders
      and passengers to wear helmets has been thoroughly implemented nation wide and
      the results show that high wearing has been sustained. Further study is required
      on how high helmet wearing has and will translate into a reduction in motorcycle
      head injuries; however, Viet Nam's motorcycle helmet legislation should be seen
      as an important policy example for other low- and middle-income countries with a
      high utilization of motorcycles for personal transport.

PMID- 22849322
TI  - Low number of memory B cells in the salivary glands of patients with primary
      Sjogren's syndrome.
AB  - We have previously shown that patients with primary Sjogren's Syndrome (pSS) show
      a significant reduction of autoantigen specific CD27(+) memory B cells and an
      abnormally elevated level of autoantibody producing plasma cells in peripheral
      blood (PB) compared to controls. Because both memory B cells and plasma cells
      have been detected in salivary glands (SG) of pSS patients, we aimed to study the
      B cell pattern in SG biopsies. Double immunohistochemical staining of CD20 and
      CD27 was carried out on paraffin-embedded SG tissue from 10 pSS patients to
      distinguish CD20(+)/CD27(+) memory B cells, and identify the CD20(+) glandular B
      cell zones (BCZ). Given that plasma blasts and plasma cells are CD27(++) and
      CD20(- ), additional CD138 single staining of serial sections allowed the
      distinction of CD27(++)/CD138(- ) plasma blasts located within the BCZ from
      CD27(++)/CD138(+) plasma cells that were found mostly on the periphery of the BCZ
      and also observed interstitially. Both BCZ and the memory B cell populations were
      then quantified. Contrary to what has been reported earlier through
      immunoflourescent staining of memory B cells in SG tissue, we have shown that
      there is a low number of memory B cells located within the glandular BCZ. Plasma
      blasts and plasma cells, however, were more abundant in the SG. Together our
      findings suggest that these low numbers of memory B cells in both PB and SG of
      pSS patients may be the result of activation of these cells into plasma cells at
      the site of inflammation.

PMID- 22849323
TI  - The involvement of serum serotonin levels producing radiation-induced bystander
      effects for an in vivo assay with fractionated high dose-rate (HDR)
      brachytherapy.
AB  - PURPOSE: The primary goal of this investigation was to observe whether measurable
      levels of bystander factor(s) can be detected in esophageal carcinoma patients'
      urine samples taken after undergoing high dose rate (HDR) intraluminal
      brachytherapy (ILBT). However, a small pilot study was developed to evaluate
      whether serotonin [5-Hydroxytryptamine (5-HT)] serum levels play an active role
      in the mechanisms of radiation-induced bystander effects (RIBE) at high doses.
      MATERIALS AND METHODS: In the present study, a colony-forming in vivo assay was
      developed and used for the detection of non-targeted effects. Samples of urine
      were collected from five esophageal carcinoma patients undergoing fractionated
      HDR-ILBT. To observe whether 5-HT modulates the bystander effect at higher doses,
      different batches of foetal bovine serum (FBS) and 5-HT were tested on the same
      urine samples before and after brachytherapy. RESULTS: Some of our data suggests
      statistically significant evidence for serotonin playing an active role as a
      signalling molecule at higher doses when patients underwent HDR-ILBT. CONCLUSION:
      However, a more thorough investigation, with a larger sample size, is warranted
      before serotonin can be known to play a role in bystander effects at this
      particular dose range and treatment regime.

PMID- 22849324
TI  - Surgical outcomes in steroid refractory acute severe ulcerative colitis: the
      impact of rescue therapy.
AB  - AIM: The advent of rescue medical therapy (cyclosporin or infliximab) and
      laparoscopic surgery has shifted the paradigm in managing steroid refractory
      acute severe ulcerative colitis (ASUC). We investigated prospectively the impact
      of rescue therapy on timing and postoperative complications of urgent colectomy
      and subsequent restorative surgery for steroid refractory ASUC. METHOD: All
      consecutive presentations of steroid refractory ASUC at the Royal Brisbane
      Hospital (1996-2009) were entered in the study. Data collated included
      demographics, clinical and laboratory parameters on admission, medical therapy
      and operative and postoperative details. Steroid refractory ASUC patients
      undergoing immediate colectomy were compared with those failing rescue therapy
      and requiring same admission colectomy. RESULTS: Of 108 steroid refractory ASUC
      presentations, 19 (18%) received intravenous steroids only and proceeded directly
      to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30
      (34%) failing to respond and proceeding to colectomy. There was no significant
      difference in the median time from admission to colectomy for rescue therapy
      compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication
      rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent
      restorative procedure was significantly longer for patients who failed rescue
      therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following
      pouch surgery were significantly higher in patients who failed rescue therapy
      (32%vs 0%, P = 0.01). CONCLUSION: Rescue therapy in steroid refractory ASUC is
      not related to delay in urgent colectomy or increased post-colectomy
      complications.

PMID- 22849325
TI  - Multiple microRNAs induced by Cdx1 suppress Cdx2 in human colorectal tumour
      cells.
AB  - The mammalian transcriptional factors, Cdx1 and Cdx2 (Cdx is caudal-type
      homeobox) are paralogues and critical for the cellular differentiation of
      intestinal or colorectal epithelia. It has been reported previously that in Cdx1
      transgenic or knockout mice, endogenous Cdx2 levels are inversely correlated with
      Cdx1 levels. Recently, we found that exogenous Cdx1 expression can suppress Cdx2
      in a human colorectal tumour cell line, SW480, although the underlying molecular
      mechanisms were unclear. In the present study, we show that several microRNAs
      induced by exogenous Cdx1 expression directly bind to the CDX2 mRNA 3'UTR
      (untranslated region) to destabilize these transcripts, finally leading to their
      degradation. Using microarray analysis, we found that several miRNAs that were
      computationally predicted to target CDX2 mRNAs are up-regulated by exogenous Cdx1
      expression in SW480 cells. Among these molecules, we identified miR-9, miR-16 and
      miR-22 as having the potential to suppress Cdx2 through the binding of the 3'UTR
      to its transcript. Importantly, simultaneous mutations of both the miR-9- and miR
      16-binding sites in the CDX2 3'UTR were shown to be sufficient to block Cdx2
      suppression. The results of the present study suggest a unique feature of miRNAs
      in which they contribute to homoeostasis by limiting the levels of transcription
      factors belonging to the same gene family.

PMID- 22849326
TI  - Structures and phase transitions of CePd3+xGa8-x: new variants of the BaHg11
      structure type.
AB  - New distorted variants of the cubic BaHg11 structure type have been synthesized
      in Ga flux. Multiple phases of CePd3+xGa8-x, which include an orthorhombic Pmmn
      structure (x = 3.21(2)), a rhombohedral R3m structure (x = 3.13(4)), and a cubic
      Fm3m superstructure (x = 2.69(6)), form preferentially depending on reaction
      cooling rate and isolation temperature. Differential thermal analysis and in situ
      temperature-dependent powder X-ray diffraction patterns show a reversible phase
      transition at approximately 640  degrees C between the low temperature
      orthorhombic and rhombohedral structures and the high temperature cubic
      superstructure. Single crystal X-ray diffraction experiments indicate that the
      general structure of BaHg11, including the intersecting planes of a kagome-type
      arrangement of Ce atoms, is only slightly distorted in the low temperature
      phases. A combination of Kondo, crystal electric field, and magnetic frustration
      effects may be present, resulting in low temperature anomalies in magnetic
      susceptibility, electrical resistivity, and heat capacity measurements. In
      addition to CePd3+xGa8-x, the rare earth analogues REPd3+xGa8-x, RE = La, Nd, Sm,
      Tm, and Yb, were successfully synthesized and also crystallize in one of the
      lower symmetry space groups.

PMID- 22849327
TI  - Age-dependent trade-offs between immunity and male, but not female, reproduction.
AB  - Immune function is costly and must be traded off against other life-history
      traits, such as gamete production. Studies of immune trade-offs typically focus
      on adult individuals, yet the juvenile stage can be a highly protracted period
      when reproductive resources are acquired and immune challenges are ubiquitous.
      Trade-offs during development are likely to be important, yet no studies have
      considered changes in adult responses to immune challenges imposed at different
      stages of juvenile development. By manipulating the timing of a bacterial immune
      challenge to the larvae of the cotton bollworm moth, we examined potential trade
      offs between investment into immunity at different stages of juvenile development
      (early or late) and subsequent adult reproductive investment into sperm or egg
      production. Our data reveal an age-dependent trade-off between juvenile immune
      function and adult male reproductive investment. Activation of the immune
      response during late development resulted in a reduced allocation of resources to
      eupyrene (fertilizing) sperm production. Immune activation from the injection
      procedure itself (irrespective of whether individuals were injected with an
      immune elicitor or a control solution) also caused reproductive trade-offs; males
      injected early in development produced fewer apyrene (nonfertilizing) sperm.
      Contrary to many other studies, our study demonstrates these immune trade-offs
      under ad libitum nutritional conditions. No trade-offs were observed between
      female immune activation and adult reproductive investment. We suggest the
      differences in trade-offs observed between male sperm types and the absence of
      reproductive trade-offs in females may be the result of ontogenetic differences
      in gamete production in this species. Our data reveal developmental windows when
      trade-offs between immune function and gametic investment are made, and highlight
      the importance of considering multiple developmental periods when making
      inferences regarding the fundamental trade-offs expected between immune function
      and reproduction.

PMID- 22849328
TI  - Homoepitaxial branching: an unusual polymorph of zinc oxide derived from seeded
      solution growth.
AB  - The development of hydrothermal synthesis has greatly promoted bottom-up
      nanoscience for the rational growth of diverse zinc oxide (ZnO) nanostructures.
      In comparison with normal ZnO nanowires, ZnO nanostructures with a larger surface
      area, for instance, branched nanowires, are more attractive in the application
      fields of catalysis, sensing, dye-sensitized solar cells etc. So far the ZnO
      branched nanowires achieved by either one-step or multistep growth always present
      a boundary-governed nonepitaxial branch/stem interface. In this report, seeded
      growth of single-crystalline ZnO hexabranched nanostructures was achieved by
      selecting polyethylene glycol (PEG) as capping agent based on a low-temperature,
      laterally epitaxial solution growth strategy. We investigated the generality of
      this PEG-assisted growth process using different ZnO seed layers including
      continuous film, patterned dots, and vertically aligned nanowire arrays. It was
      revealed that PEG is a distinctive c-direction inhibitor responsible for the
      lateral growth and subsequent branching of ZnO due to its nonionic and nonacidic
      feature and weak reactivity in the solution system. All the obtained branched
      nanostructures are of single crystallinity in nature, which is methodologically
      determined by the homoepitaxial growth mode. This PEG-assisted process is
      versatile for diameter tuning and branch formation of ZnO nanowires by secondary
      growth. Our proof-of-concept experiments demonstrated that the ZnO hexabranched
      nanostructures presented superior photocatalytic efficiency for dye degradation
      relative to the normal ZnO nanowires.

PMID- 22849330
TI  - Distribution of the Vasotocin Subtype Four Receptor (VT4R) in the Anterior
      Pituitary Gland of the Chicken, Gallus gallus, and its Possible Role in the Avian
      Stress Response.
AB  - The neurohormone arginine vasotocin (AVT) in non mammalian vertebrates is
      homologous to arginine vasopressin (AVP) in mammals. Its actions are mediated via
      G protein-coupled receptors that belong to the vasotocin/mesotocin family.
      Because of the known regulatory effects of nonapeptide hormones on anterior
      pituitary functions, receptor subtypes in that family have been proposed to be
      located in anterior pituitary cells. Recently, an avian vasotocin receptor
      subtype designated VT4R has been cloned, which shares 69% sequence homology with
      a human vasopressin receptor, the V1aR. In the present study, a polyclonal
      antibody to the VT4R was developed and validated to confirm its specificity to
      the VT4R. The antibody was used to test the hypothesis that the VT4R is present
      in the avian anterior pituitary and is specifically associated with certain cell
      types, where its expression is modulated by acute stress. Western blotting of
      membrane protein extracts from pituitary tissue, the use of HeLa cells
      transfected with the VT4R and peptide competition assays all confirmed the
      specificity of the antibody to the VT4R. Dual-labelling immunofluorescence
      microscopy was utilised to identify pituitary cell types that contained
      immunoreactive VT4R. The receptor was found to be widely distributed throughout
      the cephalic lobe but not in the caudal lobe of the anterior pituitary.
      Immunoreactive VT4R was associated with corticotrophs. Approximately 89% of
      immunolabelled corticotrophs were shown to contain the VT4R. The immunoreactive
      VT4R was not found in gonadotrophs, somatotrophs or lactotrophs. To determine a
      possible functional role of the VT4R and previously characterised VT2R, gene
      expression levels in the anterior pituitary were determined after acute
      immobilisation stress by quantitative reverse transcriptase-polymerase chain
      reaction. The results showed a significant increase in plasma corticosterone
      levels (three- to four-fold), a significant reduction of VT4R mRNA and an
      increase of VT2R mRNA (P < 0.05) in acutely immobilised chicks compared to
      controls. The data suggest a role of the VT4R in the avian stress response.

PMID- 22849331
TI  - Dose response of Gabapentin Enacarbil versus placebo in subjects with moderate-to
      severe primary restless legs syndrome: an integrated analysis of three 12-week
      studies.
AB  - BACKGROUND: The efficacy and tolerability of gabapentin enacarbil (Horizant(r);
      GlaxoSmithKline, Brentford, UK) has been demonstrated in several restless legs
      syndrome (RLS) phase II and phase III clinical studies at various doses from 600
      mg to 2400 mg. OBJECTIVE: The objective of this study was to evaluate key
      efficacy and safety outcomes in subjects with RLS treated with once-daily
      gabapentin enacarbil 600 mg, 1200 mg, 1800 mg and 2400 mg, providing supportive
      evidence of the efficacy of gabapentin enacarbil 600 mg compared with higher
      doses and placebo. STUDY DESIGN: Integrated post hoc analysis of three 12-week,
      randomized, double-blind, placebo-controlled trials in subjects with RLS.
      SETTING: The three studies were carried out at multiple centres in the US.
      PATIENTS: In total, 760 subjects were included in the pooled analysis (placebo, n
      = 245; gabapentin enacarbil 600 mg, n = 163; gabapentin enacarbil 1200 mg, n =
      269; gabapentin enacarbil 1800 mg, n = 38; gabapentin enacarbil 2400 mg, n = 45).
      INTERVENTION: In all studies, gabapentin enacarbil or placebo was administered
      once daily at approximately 5 p.m. with food. Gabapentin enacarbil was initiated
      at a dose of 600 mg with subsequent titration in 600 mg increments every 3 days
      up to the randomized dose. MAIN OUTCOME MEASURE: The efficacy endpoints analysed
      for the purpose of this integrated analysis were change from baseline in
      International Restless Legs Scale (IRLS) total score and the proportion of
      responders (subjects rated as 'much' or 'very much' improved) on the investigator
      rated Clinical Global Impression-Improvement (CGI-I) scale. Safety endpoints
      assessed were the incidence of treatment-emergent adverse events (AEs) and
      serious AEs. RESULTS: Gabapentin enacarbil 600 mg significantly improved IRLS
      total score compared with placebo (adjusted mean [standard error] change in IRLS
      total score from baseline to week 12 last observation carried forward: -13.6
      [0.71] vs -9.3 [0.55]; adjusted mean treatment difference: -4.3; 95% CI -6.01, 
      2.52; p < 0.0001). A significantly higher proportion of subjects was rated as
      responders on the investigator-rated CGI-I scale with gabapentin enacarbil 600 mg
      compared with placebo (70.2% vs 42.2%; adjusted odds ratio 3.1; 95% CI 1.96,
      4.89; p < 0.0001). Similar treatment benefits were seen with both efficacy
      endpoints for the three higher doses. The AEs reported most frequently were
      somnolence and dizziness; there was a dose-response relationship to these AEs. No
      new or unexpected safety issues were identified by this integrated analysis.
      CONCLUSION: The lowest dose of gabapentin enacarbil evaluated (600 mg)
      significantly improved RLS symptoms compared with placebo. The safety profile was
      consistent with that described previously in the literature.

PMID- 22849329
TI  - Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging
      model.
AB  - BACKGROUND: Gut microbes influence animal health and thus, are potential targets
      for interventions that slow aging. Live E. coli provides the nematode worm
      Caenorhabditis elegans with vital micronutrients, such as folates that cannot be
      synthesized by animals. However, the microbe also limits C. elegans lifespan.
      Understanding these interactions may shed light on how intestinal microbes
      influence mammalian aging. RESULTS: Serendipitously, we isolated an E. coli
      mutant that slows C. elegans aging. We identified the disrupted gene to be aroD,
      which is required to synthesize aromatic compounds in the microbe. Adding back
      aromatic compounds to the media revealed that the increased C. elegans lifespan
      was caused by decreased availability of para-aminobenzoic acid, a precursor to
      folate. Consistent with this result, inhibition of folate synthesis by
      sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans
      lifespan. As expected, these treatments caused a decrease in bacterial and worm
      folate levels, as measured by mass spectrometry of intact folates. The folate
      cycle is essential for cellular biosynthesis. However, bacterial proliferation
      and C. elegans growth and reproduction were unaffected under the conditions that
      increased lifespan. CONCLUSIONS: In this animal:microbe system, folates are in
      excess of that required for biosynthesis. This study suggests that microbial
      folate synthesis is a pharmacologically accessible target to slow animal aging
      without detrimental effects.

PMID- 22849332
TI  - Rationalization of paclitaxel insensitivity of yeast beta-tubulin and human
      betaIII-tubulin isotype using principal component analysis.
AB  - BACKGROUND: The chemotherapeutic agent paclitaxel arrests cell division by
      binding to the hetero-dimeric protein tubulin. Subtle differences in tubulin
      sequences, across eukaryotes and among beta-tubulin isotypes, can have profound
      impact on paclitaxel-tubulin binding. To capture the experimentally observed
      paclitaxel-resistance of human betaIII tubulin isotype and yeast beta-tubulin,
      within a common theoretical framework, we have performed structural principal
      component analyses of beta-tubulin sequences across eukaryotes. RESULTS: The
      paclitaxel-resistance of human betaIII tubulin isotype and yeast beta-tubulin
      uniquely mapped on to the lowest two principal components, defining the
      paclitaxel-binding site residues of beta-tubulin. The molecular mechanisms behind
      paclitaxel-resistance, mediated through key residues, were identified from
      structural consequences of characteristic mutations that confer paclitaxel
      resistance. Specifically, Ala277 in betaIII isotype was shown to be crucial for
      paclitaxel-resistance. CONCLUSIONS: The present analysis captures the origin of
      two apparently unrelated events, paclitaxel-insensitivity of yeast tubulin and
      human betaIII tubulin isotype, through two common collective sequence vectors.

PMID- 22849333
TI  - Reduced rhinovirus-specific antibodies are associated with acute exacerbations of
      chronic obstructive pulmonary disease requiring hospitalisation.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD)
      are often linked to respiratory infections. However, it is unknown if COPD
      patients who experience frequent exacerbations have impaired humoral immunity.
      The aim of this study was to determine if antibodies specific for common
      respiratory pathogens are associated with AECOPD. METHODS: Plasma was obtained
      from COPD patients when clinically stable. AECOPD requiring hospitalisation were
      recorded. IgG1 antibodies to H. Influenzae outer membrane protein 6 (P6),
      pneumococcal surface protein C (PspC) and the VP1 viral capsid protein of
      rhinovirus were measured. RESULTS: COPD patients who had an AECOPD (n = 32) had
      significantly lower anti-VP1 IgG1 antibody levels when stable compared to COPD
      patients who did not have an AECOPD (n = 28, p = 0.024). Furthermore, the number
      of hospitalisations was inversely proportional to anti-VP1 antibody levels (r = 
      0.331, p = 0.011). In contrast, antibodies specific for P6 and PspC were present
      at similar concentrations between groups. Plasma IL-21, a cytokine important for
      B-cell development and antibody synthesis, was also lower in COPD patients who
      had an AECOPD, than in stable COPD patients (p = 0.046). CONCLUSION: Deficient
      humoral immunity specific for rhinoviruses is associated with AECOPD requiring
      hospitalisation, and may partly explain why some COPD patients have an increased
      exacerbation risk following respiratory viral infections.

PMID- 22849334
TI  - Genome-wide SNP discovery in walnut with an AGSNP pipeline updated for SNP
      discovery in allogamous organisms.
AB  - BACKGROUND: A genome-wide set of single nucleotide polymorphisms (SNPs) is a
      valuable resource in genetic research and breeding and is usually developed by re
      sequencing a genome. If a genome sequence is not available, an alternative
      strategy must be used. We previously reported the development of a pipeline
      (AGSNP) for genome-wide SNP discovery in coding sequences and other single-copy
      DNA without a complete genome sequence in self-pollinating (autogamous) plants.
      Here we updated this pipeline for SNP discovery in outcrossing (allogamous)
      species and demonstrated its efficacy in SNP discovery in walnut (Juglans regia
      L.). RESULTS: The first step in the original implementation of the AGSNP pipeline
      was the construction of a reference sequence and the identification of single
      copy sequences in it. To identify single-copy sequences, multiple genome
      equivalents of short SOLiD reads of another individual were mapped to shallow
      genome coverage of long Sanger or Roche 454 reads making up the reference
      sequence. The relative depth of SOLiD reads was used to filter out repeated
      sequences from single-copy sequences in the reference sequence. The second step
      was a search for SNPs between SOLiD reads and the reference sequence.
      Polymorphism within the mapped SOLiD reads would have precluded SNP discovery;
      hence both individuals had to be homozygous. The AGSNP pipeline was updated here
      for using SOLiD or other type of short reads of a heterozygous individual for
      these two principal steps. A total of 32.6X walnut genome equivalents of SOLiD
      reads of vegetatively propagated walnut scion cultivar 'Chandler' were mapped to
      48,661 'Chandler' bacterial artificial chromosome (BAC) end sequences (BESs)
      produced by Sanger sequencing during the construction of a walnut physical map. A
      total of 22,799 putative SNPs were initially identified. A total of 6,000
      Infinium II type SNPs evenly distributed along the walnut physical map were
      selected for the construction of an Infinium BeadChip, which was used to genotype
      a walnut mapping population having 'Chandler' as one of the parents. Genotyping
      results were used to adjust the filtering parameters of the updated AGSNP
      pipeline. With the adjusted filtering criteria, 69.6% of SNPs discovered with the
      updated pipeline were real and could be mapped on the walnut genetic map. A total
      of 13,439 SNPs were discovered by BES re-sequencing. BESs harboring SNPs were in
      677 FPC contigs covering 98% of the physical map of the walnut genome.
      CONCLUSION: The updated AGSNP pipeline is a versatile SNP discovery tool for a
      high-throughput, genome-wide SNP discovery in both autogamous and allogamous
      species. With this pipeline, a large set of SNPs were identified in a single
      walnut cultivar.

PMID- 22849335
TI  - Patients with organic acidaemias have an altered thiol status.
AB  - AIM: To study whether patients with organic acidaemias have altered glutathione
      (GSH) levels and thiol redox status. Previously, organic acidaemias have been
      associated with mitochondrial dysfunction and oxidative stress, suggesting an
      increased need for antioxidant protection. Furthermore, dietary protein
      restriction may impair GSH synthesis in these diseases. METHODS: In children with
      organic acidaemias, cysteine (CYSH) and GSH concentrations in plasma and
      erythrocytes as well as erythrocyte GSH peroxidase, GSH reductase, GSH S
      transferase and glucose-6-phosphate dehydrogenase activities were studied. In
      addition, GSH and CYSH concentrations were measured in human fibroblasts exposed
      to organic acids. RESULTS: Patients with organic acidaemias had lower plasma GSH
      concentration than their controls. A greater fraction of GSH and CYSH in the
      patients' plasma was oxidized, suggesting decreased GSH synthesis and increased
      consumption. CONCLUSION: Patients with organic acidaemias may have a relative GSH
      deficiency. With further research, these results could also have therapeutic
      implications.

PMID- 22849336
TI  - Determining optimal medical image compression: psychometric and image distortion
      analysis.
AB  - BACKGROUND: Storage issues and bandwidth over networks have led to a need to
      optimally compress medical imaging files while leaving clinical image quality
      uncompromised. METHODS: To determine the range of clinically acceptable medical
      image compression across multiple modalities (CT, MR, and XR), we performed
      psychometric analysis of image distortion thresholds using physician readers and
      also performed subtraction analysis of medical image distortion by varying
      degrees of compression. RESULTS: When physician readers were asked to determine
      the threshold of compression beyond which images were clinically compromised, the
      mean image distortion threshold was a JPEG Q value of 23.1 +/- 7.0. In Receiver
      Operator Characteristics (ROC) plot analysis, compressed images could not be
      reliably distinguished from original images at any compression level between Q =
      50 and Q = 95. Below this range, some readers were able to discriminate the
      compressed and original images, but high sensitivity and specificity for this
      discrimination was only encountered at the lowest JPEG Q value tested (Q = 5).
      Analysis of directly measured magnitude of image distortion from subtracted image
      pairs showed that the relationship between JPEG Q value and degree of image
      distortion underwent an upward inflection in the region of the two thresholds
      determined psychometrically (approximately Q = 25 to Q = 50), with 75 % of the
      image distortion occurring between Q = 50 and Q = 1. CONCLUSION: It is possible
      to apply lossy JPEG compression to medical images without compromise of clinical
      image quality. Modest degrees of compression, with a JPEG Q value of 50 or higher
      (corresponding approximately to a compression ratio of 15:1 or less), can be
      applied to medical images while leaving the images indistinguishable from the
      original.

PMID- 22849337
TI  - Randomized, controlled trial of carvedilol versus nadolol plus isosorbide
      mononitrate for the prevention of variceal rebleeding.
AB  - BACKGROUND AND AIM: Carvedilol has been shown to be more effective than
      propranolol in decreasing portal pressure. Sufficient data from controlled trials
      remains limited. This trial compared the relative safety and efficacy between
      carvedilol and nadolol plus isosorbide mononitrate in preventing variceal
      rebleeding. METHODS: After successful control of acute esophageal variceal
      bleeding, eligible patients were randomized to the carvedilol group, 61 patients,
      using carvedilol 6.25-12.5 mg daily or the N + I group, 60 patients, using
      nadolol 40-80 mg plus isorsorbide-5-mononitrate 20 mg daily. The end points were
      rebleeding from varices, adverse events or death. RESULTS: After a median follow
      up of 30 months, recurrent upper gastrointestinal bleeding developed in 37
      patients (61%) in the carvedilol group and 37 patients (62%) in the N + I group
      (P = 0.90). Recurrent bleeding from esophageal varices occurred in 31 patients
      (51%) in the carvedilol group and in 26 patients (43%) in the N + I group (P =
      0.46). Recurrent bleeding from gastric varices occurred in two patients (3%) in
      the carvedilol group and in eight patients (13%) in the N + I group (P = 0.05).
      Severe adverse events occurred in one patient in the carvedilol group and 17
      patients in the N + I group (P < 0.0001). Fifteen patients of the carvedilol
      group and 17 patients in the N + I group died (P = 0.83). Two patients in the
      carvedilol group and three patients in the N + I group died of variceal bleeding.
      CONCLUSIONS: Carvedilol was as effective as nadolol plus isorsorbide-5 
      mononitrate mononitrate in the prevention of gastroesophageal variceal rebleeding
      with fewer severe adverse events and similar survival.

PMID- 22849338
TI  - Uptake of ricinB-quantum dot nanoparticles by a macropinocytosis-like mechanism.
AB  - BACKGROUND: There is a huge effort in developing ligand-mediated targeting of
      nanoparticles to diseased cells and tissue. The plant toxin ricin has been shown
      to enter cells by utilizing both dynamin-dependent and -independent endocytic
      pathways. Thus, it is a representative ligand for addressing the important issue
      of whether even a relatively small ligand-nanoparticle conjugate can gain access
      to the same endocytic pathways as the free ligand. RESULTS: Here we present a
      systematic study concerning the internalization mechanism of ricinB:Quantum dot
      (QD) nanoparticle conjugates in HeLa cells. Contrary to uptake of ricin itself,
      we found that internalization of ricinB:QDs was inhibited in HeLa cells
      expressing dominant-negative dynamin. Both clathrin-, Rho-dependent uptake as
      well as a specific form of macropinocytosis involve dynamin. However, the
      ricinB:QD uptake was not affected by siRNA-mediated knockdown of clathrin or
      inhibition of Rho-dependent uptake caused by treating cells with the Clostridium
      C3 transferase. RicinB:QD uptake was significantly reduced by cholesterol
      depletion with methyl-beta-cyclodextrin and by inhibitors of actin polymerization
      such as cytochalasin D. Finally, we found that uptake of ricinB:QDs was blocked
      by the amiloride analog EIPA, an inhibitor of macropinocytosis. Upon entry, the
      ricinB:QDs co-localized with dextran, a marker for fluid-phase uptake. Thus,
      internalization of ricinB:QDs in HeLa cells critically relies on a dynamin
      dependent macropinocytosis-like mechanism. CONCLUSIONS: Our results demonstrate
      that internalization of a ligand-nanoparticle conjugate can be dependent on other
      endocytic mechanisms than those used by the free ligand, highlighting the
      challenges of using ligand-mediated targeting of nanoparticles-based drug
      delivery vehicles to cells of diseased tissues.

PMID- 22849340
TI  - Estimation of free-energy differences from computed work distributions: an
      application of Jarzynski's equality.
AB  - Equilibrium free-energy differences can be computed from nonequilibrium molecular
      dynamics (MD) simulations using Jarzynski's equality (Jarzynski, C. Phys. Rev.
      Lett.1997, 78, 2690) by combining a large set of independent trajectories (path
      ensemble). Here we present the multistep trajectory combination (MSTC) method to
      compute free-energy differences, which by combining trajectories significantly
      reduces the number of trajectories necessary to generate a representative path
      ensemble. This method generates well-sampled work distributions, even for large
      systems, by combining parts of a relatively small number of trajectories carried
      out in steps. To assess the efficiency of the MSTC method, we derived analytical
      expressions and used them to compute the bias and the variance of the free-energy
      estimates along with numerically calculated values. We show that the MSTC method
      significantly reduces both the bias and variance of the free-energy estimates
      compared to the estimates obtained using single-step trajectories. In addition,
      because in the MSTC method the process is divided into steps, it is feasible to
      compute the reverse transition. By combining the forward and reverse processes,
      the free-energy difference can be computed using the Crooks' fluctuation theorem
      (Crooks, G. E. J. Stat. Phys.1998, 90, 1481 and Crooks, G. E. Phys. Rev. E 2000,
      61, 2361) or Bennett's acceptance ratio (Bennett, C. H. J. Comput. Phys. 1976,
      22, 245), which further reduces the bias and variance of the estimates.

PMID- 22849339
TI  - Comparison of traditional cardiovascular risk models and coronary atherosclerotic
      plaque as detected by computed tomography for prediction of acute coronary
      syndrome in patients with acute chest pain.
AB  - OBJECTIVES: The objective was to determine the association of four clinical risk
      scores and coronary plaque burden as detected by computed tomography (CT) with
      the outcome of acute coronary syndrome (ACS) in patients with acute chest pain.
      The hypothesis was that the combination of risk scores and plaque burden improved
      the discriminatory capacity for the diagnosis of ACS. METHODS: The study was a
      subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted
      Tomography (ROMICAT) trial-a prospective observational cohort study. The authors
      enrolled patients presenting to the emergency department (ED) with a chief
      complaint of acute chest pain, inconclusive initial evaluation (negative
      biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary
      artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row
      cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers,
      and subsequent diagnostic testing, such as exercise treadmill testing, nuclear
      stress perfusion imaging, and/or invasive coronary angiography), as deemed
      clinically appropriate. The clinical providers were blinded to CT results. The
      chest pain score was calculated and the results were dichotomized to >=10 (high
      risk) and <10 (low-risk). Three risk scores were calculated, Goldman, Sanchis,
      and Thrombolysis in Myocardial Infarction (TIMI), and each patient was assigned
      to a low-, intermediate-, or high-risk category. Because of the low number of
      subjects in the high-risk group, the intermediate- and high-risk groups were
      combined into one. CT images were evaluated for the presence of plaque in 17
      coronary segments. Plaque burden was stratified into none, intermediate, and high
      (zero, one to four, and more than four segments with plaque). An outcome panel of
      two physicians (blinded to CT findings) established the primary outcome of ACS
      (defined as either an acute myocardial infarction or unstable angina) during the
      index hospitalization (from the presentation to the ED to the discharge from the
      hospital). Logistic regression modeling was performed to examine the association
      of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted
      models were individually fitted for the coronary plaque burden and for Goldman,
      Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested
      whether the association between risk scores and ACS persisted after controlling
      for the coronary plaque burden. The prognostic discriminatory capacity of the
      risk scores and plaque burden for ACS was assessed using c-statistics. The
      differences in area under the receiver-operating characteristic curve (AUC) and c
      statistics were tested by performing the -2 log likelihood ratio test of nested
      models. A p value <0.05 was considered statistically significant. RESULTS: Among
      368 subjects, 31 (8%) subjects were diagnosed with ACS. Goldman (AUC = 0.61),
      Sanchis (AUC = 0.71), and TIMI (AUC = 0.63) had modest discriminatory capacity
      for the diagnosis of ACS. Plaque burden was the strongest predictor of ACS (AUC =
      0.86; p < 0.05 for all comparisons with individual risk scores). The combination
      of plaque burden and risk scores improved prediction of ACS (plaque + Goldman AUC
      = 0.88, plaque + Sanchis AUC = 0.90, plaque + TIMI AUC = 0.88; p < 0.01 for all
      comparisons with coronary plaque burden alone). CONCLUSIONS: Risk scores
      (Goldman, Sanchis, TIMI) have modest discriminatory capacity and coronary plaque
      burden has good discriminatory capacity for the diagnosis of ACS in patients with
      acute chest pain. The combined information of risk scores and plaque burden
      significantly improves the discriminatory capacity for the diagnosis of ACS.

PMID- 22849341
TI  - Simulation-based training for bedside assistants can benefit experienced robotic
      prostatectomy teams.
AB  - PURPOSE: We designed a three-phase bedside assistant training course for those
      involved with robot-assisted radical prostatectomy (RARP). We also examined
      whether an experienced RARP team (>1000 cases) would perceive benefit from this
      three-phase bedside assistant training course. MATERIALS AND METHODS: The 13 RARP
      bedside assistants were identified at our institution (three surgical
      technicians, two surgical assistants, four resident trainees, and four physician
      assistants). The course consisted of three phases that were taught at three
      separate morning sessions. Phase 1 focused on robot functionality. Phase 2
      consisted of a step-by-step video session that focused on the assistant's role in
      each RARP step. Phase 3 involved three hands-on laparoscopic drills that were to
      be completed in a predetermined period. Pre- and postcourse questionnaires
      assessed learner knowledge pertaining to RARP. RESULTS: All 13 learners completed
      the three-phase training course. Nine of 13 learners thought this course would be
      beneficial, although, 9 of 13 already thought that they were good RARP assistants
      before the course. Ten of 13 learners were able to complete the hands-on drills
      in the predetermined periods. On completion of the course, every learner thought
      the course was beneficial and that it should be repeated annually. Twelve of 13
      thought that the course made them a better assistant and that their intra
      abdominal spatial orientation was greatly improved. Seven of the learners thought
      the hands-on drills were the most beneficial portion of the course, while the
      other six found the step-by-step lecture the most beneficial. CONCLUSIONS: A
      three-phase hands-on RARP bedside assistant training course is beneficial to and
      desired by an experienced RARP team at least annually.

PMID- 22849342
TI  - Large-scale transcriptome characterization and mass discovery of SNPs in globe
      artichoke and its related taxa.
AB  - Cynara cardunculus (2n = 2* = 34) is a member of the Asteraceae family that
      contributes significantly to the agricultural economy of the Mediterranean basin.
      The species includes two cultivated varieties, globe artichoke and cardoon, which
      are grown mainly for food. Cynara cardunculus is an orphan crop species whose
      genome/transcriptome has been relatively unexplored, especially in comparison to
      other Asteraceae crops. Hence, there is a significant need to improve its genomic
      resources through the identification of novel genes and sequence-based markers,
      to design new breeding schemes aimed at increasing quality and crop productivity.
      We report the outcome of cDNA sequencing and assembly for eleven accessions of C.
      cardunculus. Sequencing of three mapping parental genotypes using Roche 454
      Titanium technology generated 1.7 * 106 reads, which were assembled into 38,726
      reference transcripts covering 32 Mbp. Putative enzyme-encoding genes were
      annotated using the KEGG-database. Transcription factors and candidate resistance
      genes were surveyed as well. Paired-end sequencing was done for cDNA libraries of
      eight other representative C. cardunculus accessions on an Illumina Genome
      Analyzer IIx, generating 46 * 106 reads. Alignment of the IGA and 454 reads to
      reference transcripts led to the identification of 195,400 SNPs with a Bayesian
      probability exceeding 95%; a validation rate of 90% was obtained by Sanger
      sequencing of a subset of contigs. These results demonstrate that the integration
      of data from different NGS platforms enables large-scale transcriptome
      characterization, along with massive SNP discovery. This information will
      contribute to the dissection of key agricultural traits in C. cardunculus and
      facilitate the implementation of marker-assisted selection programs.

PMID- 22849343
TI  - Nevada's Infant at Work Program.

PMID- 22849344
TI  - Use of the Tower of London - Drexel University, Second Edition (TOLDX) in adults
      with traumatic brain injury.
AB  - The Tower of London - Drexel University, Second Edition (TOL(DX)) was
      investigated in order to determine the efficacy of using this instrument in
      evaluating the impact of traumatic brain injury on cognitive functioning in
      adults. Performance on the TOL(DX) was compared among 56 individuals with
      complicated mild to severe traumatic brain injury ("sTBI"), 68 individuals with
      uncomplicated, mild traumatic brain injury ("mTBI"), and 124 demographically
      matched, healthy controls. Both TBI groups performed worse than controls on
      TOL(DX) measures of executive time (ET) and number of moves used (TMS), but only
      patients with sTBI were more likely to be impaired on TMS (i.e., performing at
      least 1.5 SD below the mean). Poorer performance on TMS was associated with
      increasing length of coma. Although poor sensitivity of this measure limits its
      use in isolation, the TOL(DX) may provide a complementary measurement of aspects
      of problem-solving deficit in TBI that may not be captured by other tests.

PMID- 22849345
TI  - Regression-based norms improve the sensitivity of the National MS Society
      Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS).
AB  - The National Multiple Sclerosis Society Consensus Neuropsychological Battery for
      Pediatric Multiple Sclerosis (NBPMS) was designed to detect cognitive impairment
      in children and adolescents with multiple sclerosis. One weakness of the battery
      is the reliance on published manual-based normative samples varying in size and
      quality. These primary sources base interpretation on discrete age bands, a
      practice which may be particularly problematic during periods of rapid
      development in childhood and adolescence. A further impediment to valid NBPMS
      interpretation is the lack of control for demographic factors other than age. We
      endeavored to develop regression-based norms for the NBPMS by gathering a
      demographically balanced sample of 102 healthy control children and using their
      performance to derive normalization, controlling for multiple demographic
      variables (i.e., age, age(2), gender, parent education). The regression-based
      normative equations were applied to the performance of 51 children with MS. For
      many of the major test scores, the regression-based norms more readily detected
      impairment. As in the case of adult MS, these results indicate that regression
      based norms offer interpretive benefits over their manual-based counterparts.

PMID- 22849348
TI  - Effects of rotation frequency and task order on localised muscle fatigue and
      performance during repetitive static shoulder exertions.
AB  - Though widely considered to reduce physical exposures and increase exposure
      variation, there is limited evidence that rotating between tasks is effective in
      reducing the risk of work-related musculoskeletal disorders (WMSDs). The purpose
      of this study was to assess the effects of rotation, specifically focusing on
      rotation frequency and task order, on muscle fatigue and performance when
      rotating between tasks that load the same muscle group. Twelve participants
      completed six experimental sessions during which repetitive static shoulder
      abduction tasks were performed at two exertion levels for one hour either with or
      without rotation. Compared to only performing a higher or lower exertion task,
      rotating between the two tasks decreased and increased fatigue, respectively.
      Increasing rotation frequency adversely affected task performance, and task order
      had a minor effect on muscle fatigue. These rotation parameters may be important
      considerations when implementing rotation in the workplace. PRACTITIONER SUMMARY:
      Rotation is widely used and assumed to reduce the risk of WMSDs, yet little
      research supports that it is effective in doing so. Results here show that
      specific aspects of a rotation scheme may influence muscle fatigue and task
      performance, though further research is needed under more realistic task
      conditions.

PMID- 22849347
TI  - Crystal structure of the human NKX2.5 homeodomain in complex with DNA target.
AB  - NKX2.5 is a homeodomain containing transcription factor regulating cardiac
      formation and function, and its mutations are linked to congenital heart disease.
      Here we provide the first report of the crystal structure of the NKX2.5
      homeodomain in complex with double-stranded DNA of its endogenous target,
      locating within the proximal promoter -242 site of the atrial natriuretic factor
      gene. The crystal structure, determined at 1.8 A resolution, demonstrates that
      NKX2.5 homeodomains occupy both DNA binding sites separated by five nucleotides
      without physical interaction between themselves. The two homeodomains show
      identical conformation despite the differences in the DNA sequences they bind,
      and no significant bending of the DNA was observed. Tyr54, absolutely conserved
      in NK2 family proteins, mediates sequence-specific interaction with the TAAG
      motif. This high resolution crystal structure of NKX2.5 protein provides a
      detailed picture of protein and DNA interactions, which allows us to predict DNA
      binding of mutants identified in human patients.

PMID- 22849349
TI  - Protein kinase Cepsilon activity induces anti-inflammatory and anti-apoptotic
      genes via an ERK1/2- and NF-kappaB-dependent pathway to enhance vascular
      protection.
AB  - Vascular endothelial injury predisposes to endothelial dysfunction and
      atherogenesis. We have investigated the hypothesis that PKCepsilon (protein
      kinase Cepsilon) is an important upstream regulator of cytoprotective pathways in
      vascular ECs (endothelial cells). Depletion of PKCepsilon in human ECs reduced
      expression of the cytoprotective genes A1, A20 and Bcl-2. Conversely,
      constitutively active PKCepsilon expressed in human ECs increased mRNA and
      protein levels of these cytoprotective genes, with up-regulation dependent upon
      ERK1/2 (extracellular-signal-regulated kinase 1/2) activation. Furthermore,
      inhibition of NF-kappaB (nuclear factor kappaB) by the pharmacological antagonist
      BAY 11-7085 or an IkappaB (inhibitor of NF-kappaB) SuperRepressor prevented
      cytoprotective gene induction. Activation of PKCepsilon enhanced p65 NF-kappaB
      DNA binding and elevated NF-kappaB transcriptional activity. Importantly,
      although NF-kappaB activation by PKCepsilon induced cytoprotective genes, it did
      not up-regulate pro-inflammatory NF-kappaB targets [E-selectin, VCAM-1 (vascular
      cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1)].
      Indeed, PKCepsilon exhibited cytoprotective and anti-inflammatory actions,
      including inhibition of TNFalpha (tumour necrosis factor alpha)-induced JNK (c
      Jun N-terminal kinase) phosphorylation and ICAM-1 up-regulation, a response
      attenuated by depletion of A20. Thus we conclude that PKCepsilon plays an
      essential role in endothelial homoeostasis, acting as an upstream co-ordinator of
      gene expression through activation of ERK1/2, inhibition of JNK and diversion of
      the NF-kappaB pathway to cytoprotective gene induction, and propose that
      PKCepsilon represents a novel therapeutic target for endothelial dysfunction.

PMID- 22849350
TI  - Haematological values in homozygous sickle cell disease in steady state and
      haemoglobin phenotypes AA controls in Lagos, Nigeria.
AB  - BACKGROUND: Sickle cell disease is a genetic abnormality involving the
      haemoglobin. Although, it is primarily a red cell disorders, the white blood
      cells and platelets are also affected by the mutation. The consequent haemoglobin
      S causes polymerization of haemoglobin resulting in haemolysis and anaemia. This
      study aims to provide baseline haematological values in sickle cell disease
      patients in steady state and compare the deviation from haemoglobin phenotype AA
      control values. METHODS: A case-control study was conducted amongst homozygous
      sickle cell patients attending the sickle cell clinics of Lagos State University
      Teaching Hospital Ikeja and haemoglobin phenotype AA controls. About 4.5mls of
      blood sample was collected from each participant for full blood count analysis.
      All blood samples were screened for HIV and haemoglobin phenotypes confirmed
      using cellulose acetate haemoglobin electrophoresis at pH 8.6. RESULTS: A total
      of 103 cases and 98 controls were enrolled. The overall mean haemoglobin
      concentration for cases was 7.93 +/- 1.47 g/dl, packed cell volume 24.44 +/-
      4.68%, mean cell volume 81.52 +/- 7.89 fl, and mean cell haemoglobin 26.50 +/-
      3.20 pg. While for controls, mean haemoglobin concentration was 13.83 +/- 1.32
      g/dl, packed cell volume 43.07 +/- 3.95%, mean cell volume 86.90 +/- 4.69 fl, and
      mean cell haemoglobin 28.50 +/- 1.34 pg. The overall mean white blood cell counts
      for the cases was 10.27 +/- 3.94 *103/MUl and platelet counts of 412.71 +/-
      145.09*103/MUl. While white blood cell count for the controls was 5.67 +/-
      1.59*103/MUl and platelet counts of 222.82 +/- 57.62*103/MUl. CONCLUSION:
      Homozygous sickle cell disease patients have lower values of red cell parameters,
      but higher values of white cell and platelets counts compared to haemoglobin
      phenotype AA controls.

PMID- 22849351
TI  - Management of acne scarring, part II: a comparative review of non-laser-based,
      minimally invasive approaches.
AB  - Acne scarring is a commonly encountered yet extremely challenging problem to
      treat for the dermatologist. As acne scarring can lead to significant
      psychological distress and low self-esteem, it is of utmost importance to have
      effective and satisfying treatments in the physician's armamentarium. However,
      many treatments are unsatisfying, leading to patient disappointment and
      frustration. Although early treatment of acne lesions and inflammation with
      isotretinoin is beneficial in preventing acne scarring, many patients still
      present with troubling noticeable scars. Despite the advances in pharmacology and
      technology, scar treatment still remains suboptimal and is tainted with several
      adverse effects. However, some treatments can provide benefits. This review
      article exhaustively discusses and analyzes the various minimally invasive
      approaches to the treatment of acne scarring with an emphasis on pharmacologic
      agents, such as isotretinoin for atrophic acne scars and corticosteroids and
      chemotherapeutic drugs for hypertrophic scars. Intralesional injections of
      corticosteroids are efficacious in reducing keloid scar formation in addition to
      preventing recurrence following surgical excision. In-office and minimally
      invasive procedural management, including chemical peels, dermabrasion, tissue
      augmentation, and punch excision is also discussed. Superficial chemical peels
      are efficacious in treating atrophic scars with relatively few adverse effects
      and complications. Although dermabrasion is used less often with the advent of
      laser resurfacing, this technique remains as a viable option for those with
      atrophic scars. Post-inflammatory hyperpigmentation can be managed successfully
      with topical agents such as azelaic acid and hydroquinone. The efficacy of
      various treatment modalities is highlighted with a focus on choosing the correct
      modalities for specific scar types.

PMID- 22849352
TI  - Ipilimumab: a guide to its use in advanced melanoma.
AB  - Ipilimumab (YervoyTM), a recombinant monoclonal antibody targeted at cytotoxic T
      lymphocyte-associated antigen 4, is approved for the treatment of advanced
      melanoma. In a placebo-controlled trial in previously treated patients with
      advanced melanoma, ipilimumab, without or with an investigational glycoprotein
      (gp) 100 peptide vaccine, was associated with significantly longer median overall
      survival than gp100 peptide vaccine monotherapy. The risk of death relative to
      the gp100 peptide vaccine was reduced by 34% with ipilimumab monotherapy and by
      32% with ipilimumab plus gp100 peptide vaccine. Overall survival did not differ
      significantly between treatment with ipilimumab monotherapy and ipilimumab plus
      gp100 peptide vaccine. Novel immune-related events that are not typical of other
      anticancer agents, most commonly dermatologic and gastrointestinal disorders, can
      occur with ipilimumab, necessitating specific monitoring and management
      protocols.

PMID- 22849353
TI  - Fermentation responses and in vitro radical scavenging activities of Fagopyrum
      esculentum.
AB  - In this study, the impact of fermentation of Fagopyrum esculentum (buckwheat) by
      Lactobacillus delbrueckii subsp. lactis was investigated. The interaction between
      starter culture and buckwheat dough matrix was evaluated with respect to
      microbial count, final pH, organic acids, total phenolic content and antioxidant
      potential. An increase of one log cycle from 8.76 to 9.92 log CFU(Colony Forming
      Unit)/g was observed during fermentation. Lactic acid content increased up to
      1350 MUg/g within 24 h of fermentation. The most significant result of this study
      was an observed increase in the total phenolic content of the dough, from 2.73 to
      7.64 mg GAE(Gallic Acid Equivalence)/g. Antioxidant potential of fermented
      buckwheat also showed an increased percentage of 2,2-diphenyl-2-picrylhydrazyl
      scavenging activity from 44.32% to 88.98% and ferric reducing antioxidant power
      potential increased from 14.43 to 25.68 MUM Fe(II)/g after 72 h of fermentation.
      We conclude that lactic acid fermentation of buckwheat dough has a potential to
      be a functional food, with enhanced antioxidant activity.

PMID- 22849354
TI  - The role of  tocilizumab  in the management of rheumatoid arthritis.
AB  - INTRODUCTION: The introduction of biological treatments has improved the outlook
      for patients diagnosed with rheumatoid arthritis. There are now a range of
      different agents, targeting various pathways involved in the inflammatory
      process. Tocilizumab , a fully humanised anti-interleukin-6 receptor monoclonal
      antibody is licensed for the treatment of rheumatoid arthritis and systemic
      juvenile idiopathic arthritis. AREAS COVERED: This article reviews and appraises
      the available evidence regarding the efficacy and safety of tocilizumab in
      rheumatoid arthritis, as identified in PubMed and Embase searches. EXPERT
      OPINION: Clinical trial data suggest that tocilizumab has similar efficacy both
      clinically and in reducing structural progression to that seen with the TNF
      inhibitors. Patients who might be particularly suitable for tocilizumab are those
      who have failed multiple TNF inhibitors, those with a high inflammatory response
      as part of their disease and those unable to tolerate methotrexate, given the
      good responses seen with monotherapy.

PMID- 22849355
TI  - Environmental species sorting dominates forest-bird community assembly across
      scales.
AB  - Environmental species sorting and dispersal are seen as key factors in community
      assembly, but their relative importance and scale dependence remain uncertain, as
      the extent to which communities are consistently assembled throughout their
      biomes. To address these issues, we analysed bird metacommunity structure in a
      1200-km(2)  forested landscape (Istranca Forests) in Turkish Thrace at the margin
      of the Western Palaearctic (WP) temperate-forest biome. First, we used spatial
      regressions and Mantel tests to assess the relative importance of environmental
      and spatial factors as drivers of local species richness and composition within
      the metacommunity. Second, we analysed species' abundance-occupancy relationship
      across the metacommunity and used null models to assess whether occupancy is
      determined by species' environmental niches. Third, we used generalized linear
      models to test for links between species' metacommunity-wide occupancy and their
      broader WP regional populations and assessed whether these links are consistent
      with environmental species sorting. There was strong environmental control on
      local species richness and composition patterns within the metacommunity, but non
      environmental spatial factors had also an important joint role. Null model
      analyses on randomized communities showed that species' occupancy across the
      metacommunity was strongly determined by species' environmental niches, with
      occupancy being related to niche position marginality. Species' metacommunity
      wide occupancy correlated with their local abundance as well as with their range
      size and total abundance for the whole WP, suggesting that the same assembly
      mechanisms act consistently across local to regional scales. A species
      specialization index that was estimated by bird species' habitat use across
      France, incorporating both niche position and breadth, was significantly related
      to species' occupancy and abundance at both metacommunity and WP regional scales.
      Hence, the same niche-related assembly mechanisms appear to act consistently
      across the WP region. Overall, our results suggest that the structure of the
      Istranca Forest' bird metacommunity was predominantly controlled by environmental
      species sorting in a manner consistent with the broader WP region. However,
      variability in local community structure was also linked to purely spatial
      factors, albeit more weakly.

PMID- 22849357
TI  - Leadership matters.

PMID- 22849356
TI  - Peroxisome proliferator-activated receptors gamma/mitochondrial uncoupling
      protein 2 signaling protects against seizure-induced neuronal cell death in the
      hippocampus following experimental status epilepticus.
AB  - BACKGROUND: Status epilepticus induces subcellular changes that may lead to
      neuronal cell death in the hippocampus. However, the mechanism of seizure-induced
      neuronal cell death remains unclear. The mitochondrial uncoupling protein 2
      (UCP2) is expressed in selected regions of the brain and is emerged as an
      endogenous neuroprotective molecule in many neurological disorders. We evaluated
      the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal
      cell death under experimental status epilepticus. METHODS: In Sprague-Dawley
      rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3
      subfield to induce prolonged bilateral seizure activity. Oxidized protein level,
      translocation of Bcl-2, Bax and cytochrome c between cytosol and mitochondria,
      and expression of peroxisome proliferator-activated receptors gamma (PPARgamma)
      and UCP2 were examined in the hippocampal CA3 subfield following KA-induced
      status epilepticus. The effects of microinjection bilaterally into CA3 area of a
      PPARgamma agonist, rosiglitazone or a PPARgamma antagonist, GW9662 on UCP2
      expression, induced superoxide anion (O(.2)(-)) production, oxidized protein
      level, mitochondrial respiratory chain enzyme activities, translocation of Bcl-2,
      Bax and cytochrome c, and DNA fragmentation in bilateral CA3 subfields were
      examined. RESULTS: Increased oxidized proteins and mitochondrial or cytosol
      translocation of Bax or cytochrome c in the hippocampal CA3 subfield was observed
      3-48 h after experimental status epilepticus. Expression of PPARgamma and UCP2
      increased 12-48 h after KA-induced status epilepticus. Pretreatment with
      rosiglitazone increased UCP2 expression, reduced protein oxidation, O(.2)(-)
      overproduction and dysfunction of mitochondrial Complex I, hindered the
      translocation of Bax and cytochrome c, and reduced DNA fragmentation in the CA3
      subfield. Pretreatment with GW9662 produced opposite effects. CONCLUSIONS:
      Activation of PPARgamma upregulated mitochondrial UCP2 expression, which
      decreased overproduction of reactive oxygen species, improved mitochondrial
      Complex I dysfunction, inhibited mitochondrial translocation of Bax and prevented
      cytosolic release of cytochrome c by stabilizing the mitochondrial transmembrane
      potential, leading to amelioration of apoptotic neuronal cell death in the
      hippocampus following status epilepticus.

PMID- 22849358
TI  - Plasmon inducing effects for enhanced photoelectrochemical water splitting: X-ray
      absorption approach to electronic structures.
AB  - Artificial photosynthesis using semiconductors has been investigated for more
      than three decades for the purpose of transferring solar energy into chemical
      fuels. Numerous studies have revealed that the introduction of plasmonic
      materials into photochemical reaction can substantially enhance the photo
      response to the solar splitting of water. Until recently, few systematic studies
      have provided clear evidence concerning how plasmon excitation and which factor
      dominates the solar splitting of water in photovoltaic devices. This work
      demonstrates the effects of plasmons upon an Au nanostructure-ZnO nanorods array
      as a photoanode. Several strategies have been successfully adopted to reveal the
      mutually independent contributions of various plasmonic effects under solar
      irradiation. These have clarified that the coupling of hot electrons that are
      formed by plasmons and the electromagnetic field can effectively increase the
      probability of a photochemical reaction in the splitting of water. These findings
      support a new approach to investigating localized plasmon-induced effects and
      charge separation in photoelectrochemical processes, and solar water splitting
      was used herein as platform to explore mechanisms of enhancement of surface
      plasmon resonance.

PMID- 22849359
TI  - A new approach to determining pharmacologic adulteration of herbal weight loss
      products.
AB  - Pharmaceutical adulterants are commonly found in herbal weight loss products, and
      analytical techniques for detecting these adulterants have become increasingly
      important to the public health community. Previously we reported a novel
      analytical method for the determination of adulterants in herbal formulations by
      capillary electrophoresis with contactless conductivity detection. The current
      study refines this previously described technique by testing if anxiolytics,
      diuretics, and laxatives interfered with the detection of anorectics and
      antidepressants. A survey of herbal weight loss products sold by compounding
      pharmacies in Brazil were analysed to determine the presence of pharmaceutical
      adulterants. A total of 106 herbal products, collected from 73 pharmacies in nine
      Brazilian states, were analysed for amfepramone, sibutramine, fenproporex,
      fluoxetine, paroxetine, sertraline and bupropion using the new analytical method.
      The method permitted the rapid and selective screening for the seven adulterants.
      Of the 106 weight loss products sampled, four (3.8%) were found to be adulterated
      by fenproporex or sibutramine. The adulterated samples were compounded by four
      different pharmacies located in three different Brazilian states. The novel
      capillary electrophoresis method we developed may be a useful tool for public
      health organisations tasked with analysing herbal weight loss products.

PMID- 22849361
TI  - Systematic benchmark of substructure search in molecular graphs - From Ullmann to
      VF2.
AB  - BACKGROUND: Searching for substructures in molecules belongs to the most
      elementary tasks in cheminformatics and is nowadays part of virtually every
      cheminformatics software. The underlying algorithms, used over several decades,
      are designed for the application to general graphs. Applied on molecular graphs,
      little effort has been spend on characterizing their performance. Therefore, it
      is not clear how current substructure search algorithms behave on such special
      graphs. One of the main reasons why such an evaluation was not performed in the
      past was the absence of appropriate data sets. RESULTS: In this paper, we present
      a systematic evaluation of Ullmann's and the VF2 subgraph isomorphism algorithms
      on molecular data. The benchmark set consists of a collection of 1235 SMARTS
      substructure expressions and selected molecules from the ZINC database. The
      benchmark evaluates substructures search times for complete database scans as
      well as individual substructure-molecule pairs. In detail, we focus on the
      influence of substructure formulation and size, the impact of molecule size, and
      the ability of both algorithms to be used on multiple cores. CONCLUSIONS: The
      results show a clear superiority of the VF2 algorithm in all test scenarios. In
      general, both algorithms solve most instances in less than one millisecond, which
      we consider to be acceptable. Still, in direct comparison, the VF2 is most often
      several folds faster than Ullmann's algorithm. Additionally, Ullmann's algorithm
      shows a surprising number of run time outliers.

PMID- 22849360
TI  - Dose-dependent effects of small-molecule antagonists on the genomic landscape of
      androgen receptor binding.
AB  - BACKGROUND: The androgen receptor plays a critical role throughout the
      progression of prostate cancer and is an important drug target for this disease.
      While chromatin immunoprecipitation coupled with massively parallel sequencing
      (ChIP-Seq) is becoming an essential tool for studying transcription and chromatin
      modification factors, it has rarely been employed in the context of drug
      discovery. RESULTS: Here we report changes in the genome-wide AR binding
      landscape due to dose-dependent inhibition by drug-like small molecules using
      ChIP-Seq. Integration of sequence analysis, transcriptome profiling, cell
      viability assays and xenograft tumor growth inhibition studies enabled us to
      establish a direct cistrome-activity relationship for two novel potent AR
      antagonists. By selectively occupying the strongest binding sites, AR signaling
      remains active even when androgen levels are low, as is characteristic of first
      line androgen ablation therapy. Coupled cistrome and transcriptome profiling upon
      small molecule antagonism led to the identification of a core set of AR direct
      effector genes that are most likely to mediate the activities of targeted agents:
      unbiased pathway mapping revealed that AR is a key modulator of steroid
      metabolism by forming a tightly controlled feedback loop with other nuclear
      receptor family members and this oncogenic effect can be relieved by antagonist
      treatment. Furthermore, we found that AR also has an extensive role in negative
      gene regulation, with estrogen (related) receptor likely mediating its function
      as a transcriptional repressor. CONCLUSIONS: Our study provides a global and
      dynamic view of AR's regulatory program upon antagonism, which may serve as a
      molecular basis for deciphering and developing AR therapeutics.

PMID- 22849362
TI  - Imaging and measuring single-molecule interaction between a carbohydrate-binding
      module and natural plant cell wall cellulose.
AB  - The affinitive interaction between a carbohydrate-binding module (CBM3a) and
      natural crystalline cellulose was visualized and measured at the single-molecule
      level. Noncontact high resolution imaging by atomic force microscopy (AFM) was
      used to follow the binding process, in real time, of CBM3a-functionalized 6 nm
      gold nanoparticles (GNPs) to the cell wall polymers on poplar stem sections. The
      GNP-CBM3a complexes were found to bind to the cellulose surface, closely aligning
      along the cellulose fibril axis. The binding details were further confirmed and
      studied by single-molecule recognition imaging and AFM single-molecule dynamic
      force spectroscopy (SMDFS) using a CBM3a-functionalized AFM tip. The unbinding
      force was measured to be 44.96 +/- 18.80 pN under a loading rate of 67.2 nN/s.
      This research provides a radical method for the study of single-molecule affinity
      between CBM and cellulose that is critical to the engineering of novel
      cellulolytic enzymes.

PMID- 22849363
TI  - Skin-to-skin care in neonatal intensive care units in the Nordic countries: a
      survey of attitudes and practices.
AB  - AIM: To investigate the application of skin-to-skin care (SSC) in the Nordic
      countries, the existence of guidelines for SSC and the attitudes of neonatal
      staff towards SSC. METHODS: One questionnaire was distributed at unit level and
      one at staff level in all Nordic neonatal intensive care units (n = 109).
      RESULTS: The unit questionnaire was answered by 95 (87%) units and the staff
      questionnaire by 1446 staff members (72%). All units offered SSC to various
      degrees, but guidelines only existed at 47% of them. Units in Denmark, Norway and
      Sweden seemed to use SSC earlier, longer and in more medically complicated
      situations than units in Finland and Iceland. Seventy-seven per cent of the units
      had private rooms where parents and infants could stay together, still the
      physical environment of the units limited the use of SSC. Medical risks were
      considered the main barrier for further implementation of SSC, while general
      development and early interaction were the most frequently mentioned benefits.
      CONCLUSION: Skin-to-skin care is implemented in all Nordic neonatal units, but
      offered to various degrees, to various populations and to varying extents.
      Danish, Norwegian and Swedish units are offering SSC more extensively than units
      in Finland and Iceland.

PMID- 22849364
TI  - Flexgrepps--flexible greedy peptide pool search: computation of near-optimal sets
      of degenerate polypeptides for antigenic screening.
AB  - Although synthesizing and utilizing individual peptides and DNA primers has
      become relatively inexpensive, massively parallel probing and next-generation
      sequencing approaches have dramatically increased the number of molecules that
      can be subjected to screening; this, in turn, requires vast numbers of peptides
      and therefore results in significant expenses. To alleviate this issue, pools of
      related molecules are often used to downselect prior to testing individual
      sequences. A computational selection process to create pools of related sequences
      at large scale has not been reported for peptides. In the case of PCR primers,
      there have been successful attempts to address this problem by designing
      degenerate primers that can be produced at the same cost as conventional, unique
      primers and then be used to amplify several different genomic regions. We present
      an algorithm, "FlexGrePPS" (Flexible Greedy Peptide Pool Search), that can create
      a near-optimal set of peptide pools. This approach is also applicable to
      nucleotide sequences and outperforms most DNA primer selection programs. For the
      proteomic compression with FlexGrePPS, the main body of our work presented here,
      we demonstrate the feasibility of the computation of an exhaustive cover of
      pathogenic proteomes with degenerate peptides that lend themselves to antigenic
      screening. Furthermore, we present preliminary data that demonstrate the
      experimental utility of highly degenerate peptides for antigenic screening.
      FlexGrePPS provides a near-optimal solution for proteomic compression and there
      are no programs available for comparison. We also demonstrate computational
      performance of our GreedyPrime implementation, which is a modified version of
      FlexGrePPS applicable to the design of degenerate primers and is comparable to
      existing programs for the design of degenerate primers. Specifically, we focus on
      the comparisons with PAMPS and DPS-DIP, software tools that have recently been
      shown to be superior to other methods. FlexGrePPS forms the foundation of a novel
      antigenic screening methodology that is based on the representation of an entire
      proteome by near-optimal degenerate peptide pools. Our preliminary wet lab data
      indicate that the approach will likely prove successful in comprehensive wet lab
      studies, and hence will dramatically reduce the expenses for antigenic screening
      and make whole proteome screening feasible. Although FlexGrePPS was designed for
      computational performance in order to handle vast data sets, there is the very
      surprising finding that even for small data sets the primer design version of
      FlexGrePPS, GreedyPrime, offers similar or even superior results for MP-DPD and
      most MDPD instances when compared to existing methods; despite the much longer
      run times, other approaches did not fare significantly better in reducing the
      original data sets to degenerate primers. The FlexGrePPS and GreedyPrime programs
      are available at no charge under the GNU LGPL license at
      http://sourceforge.net/projects/flexgrepps/.

PMID- 22849365
TI  - A between-class overlapping filter-based method for transcriptome data analysis.
AB  - Feature selection algorithms play a crucial role in identifying and discovering
      important genes for cancer classification. Feature selection algorithms can be
      broadly categorized into two main groups: filter-based methods and wrapper-based
      methods. Filter-based methods have been quite popular in the literature due to
      their many advantages, including computational efficiency, simplistic
      architecture, and an intuitively simple means of discovering biological and
      clinical aspects. However, these methods have limitations, and the classification
      accuracy of the selected genes is less accurate. In this paper, we propose a set
      of univariate filter-based methods using a between-class overlapping criterion.
      The proposed techniques have been compared with many other univariate filter
      based methods using an acute leukemia dataset. The following properties have been
      examined: classification accuracy of the selected individual genes and the gene
      subsets; redundancy check among selected genes using ridge regression and LASSO
      methods; similarity and sensitivity analyses; functional analysis; and, stability
      analysis. A comprehensive experiment shows promising results for our proposed
      techniques. The univariate filter based methods using between-class overlapping
      criterion are accurate and robust, have biological significance, and are
      computationally efficient and easy to implement. Therefore, they are well suited
      for biological and clinical discoveries.

PMID- 22849366
TI  - Entropy-based cluster validation and estimation of the number of clusters in gene
      expression data.
AB  - Many external and internal validity measures have been proposed in order to
      estimate the number of clusters in gene expression data but as a rule they do not
      consider the analysis of the stability of the groupings produced by a clustering
      algorithm. Based on the approach assessing the predictive power or stability of a
      partitioning, we propose the new measure of cluster validation and the selection
      procedure to determine the suitable number of clusters. The validity measure is
      based on the estimation of the "clearness" of the consensus matrix, which is the
      result of a resampling clustering scheme or consensus clustering. According to
      the proposed selection procedure the stable clustering result is determined with
      the reference to the validity measure for the null hypothesis encoding for the
      absence of clusters. The final number of clusters is selected by analyzing the
      distance between the validity plots for initial and permutated data sets. We
      applied the selection procedure to estimate the clustering results on several
      datasets. As a result the proposed procedure produced an accurate and robust
      estimate of the number of clusters, which are in agreement with the biological
      knowledge and gold standards of cluster quality.

PMID- 22849367
TI  - Inferring the regulatory interaction models of transcription factors in
      transcriptional regulatory networks.
AB  - Living cells are realized by complex gene expression programs that are moderated
      by regulatory proteins called transcription factors (TFs). The TFs control the
      differential expression of target genes in the context of transcriptional
      regulatory networks (TRNs), either individually or in groups. Deciphering the
      mechanisms of how the TFs control the differential expression of a target gene in
      a TRN is challenging, especially when multiple TFs collaboratively participate in
      the transcriptional regulation. To unravel the roles of the TFs in the regulatory
      networks, we model the underlying regulatory interactions in terms of the TF
      target interactions' directions (activation or repression) and their
      corresponding logical roles (necessary and/or sufficient). We design a set of
      constraints that relate gene expression patterns to regulatory interaction
      models, and develop TRIM (Transcriptional Regulatory Interaction Model
      Inference), a new hidden Markov model, to infer the models of TF-target
      interactions in large-scale TRNs of complex organisms. Besides, by training TRIM
      with wild-type time-series gene expression data, the activation timepoints of
      each regulatory module can be obtained. To demonstrate the advantages of TRIM, we
      applied it on yeast TRN to infer the TF-target interaction models for individual
      TFs as well as pairs of TFs in collaborative regulatory modules. By comparing
      with TF knockout and other gene expression data, we were able to show that the
      performance of TRIM is clearly higher than DREM (the best existing algorithm). In
      addition, on an individual Arabidopsis binding network, we showed that the target
      genes' expression correlations can be significantly improved by incorporating the
      TF-target regulatory interaction models inferred by TRIM into the expression data
      analysis, which may introduce new knowledge in transcriptional dynamics and
      bioactivation.

PMID- 22849368
TI  - Constructing a minimum phylogenetic network from a dense triplet set.
AB  - For a given set L of species and a set T of triplets on L, we seek to construct a
      phylogenetic network which is consistent with T i.e. which represents all
      triplets of T. The level of a network is defined as the maximum number of hybrid
      vertices in its biconnected components. When T is dense, there exist polynomial
      time algorithms to construct level-0,1 and 2 networks (Aho et al., 1981; Jansson,
      Nguyen and Sung, 2006; Jansson and Sung, 2006; Iersel et al., 2009). For higher
      levels, partial answers were obtained in the paper by Iersel and Kelk (2008),
      with a polynomial time algorithm for simple networks. In this paper, we detail
      the first complete answer for the general case, solving a problem proposed in
      Jansson and Sung (2006) and Iersel et al. (2009). For any k fixed, it is possible
      to construct a level-k network having the minimum number of hybrid vertices and
      consistent with T, if there is any, in time O(T(k+1)n([4k/3]+1)).

PMID- 22849369
TI  - Metagenomic taxonomic classification using extreme learning machines.
AB  - Next-generation sequencing technologies have allowed researchers to determine the
      collective genomes of microbial communities co-existing within diverse ecological
      environments. Varying species abundance, length and complexities within different
      communities, coupled with discovery of new species makes the problem of taxonomic
      assignment to short DNA sequence reads extremely challenging. We have developed a
      new sequence composition-based taxonomic classifier using extreme learning
      machines referred to as TAC-ELM for metagenomic analysis. TAC-ELM uses the
      framework of extreme learning machines to quickly and accurately learn the
      weights for a neural network model. The input features consist of GC content and
      oligonucleotides. TAC-ELM is evaluated on two metagenomic benchmarks with
      sequence read lengths reflecting the traditional and current sequencing
      technologies. Our empirical results indicate the strength of the developed
      approach, which outperforms state-of-the-art taxonomic classifiers in terms of
      accuracy and implementation complexity. We also perform experiments that evaluate
      the pervasive case within metagenome analysis, where a species may not have been
      previously sequenced or discovered and will not exist in the reference genome
      databases. TAC-ELM was also combined with BLAST to show improved classification
      results. Code and Supplementary Results:  http://www.cs.gmu.edu/~mlbio/TAC-ELM 
      (BSD License).

PMID- 22849370
TI  - A decade after the first full human genome sequencing: when will we understand
      our own genome?
AB  - The contrast between the pomp of celebrating the first full human genome
      sequencing in 2000 and the cautious tone of recollections a decade thereafter
      could hardly be greater. The promises with regard to medical cures and
      biotechnology applications have been realized not even nearly to the
      expectations. Understanding the human genomes means knowing the genes' and
      proteins' functions and their interconnectedness via biomolecular mechanisms.
      This articles estimates how long will it take to achieve this goal if we
      extrapolate from the previous decade (indeed, a century!) and the possible
      disruptive trends in science, technology and society that may accelerate the pace
      of progress dramatically.

PMID- 22849371
TI  - Electronic state spectroscopy of 1,4-pentadiene as studied by VUV photoabsorption
      spectroscopy and ab initio calculations.
AB  - We present high resolution VUV photoabsorption spectra of 1,4-pentadiene,
      C(5)H(8), over the wavelength range 115-247 nm (10.8-5.0 eV). These spectra
      reveal several new features not previously reported in the literature. These
      measurements are complemented by the first ab initio calculations for the three
      most abundant conformational isomers of 1,4-pentadiene, C(5)H(8), which we then
      use in the assignment of valence and Rydberg transitions. Calculations of the two
      lowest energy ionic states of 1,4-pentadiene are also presented and compared with
      the experimental data available in the literature. The measured absolute
      photoabsorption cross sections have been used to calculate the photolysis
      lifetime of 1,4-pentadiene in the upper stratosphere (20-50 km).

PMID- 22849372
TI  - Intratracheally administered titanium dioxide or carbon black nanoparticles do
      not aggravate elastase-induced pulmonary emphysema in rats.
AB  - BACKGROUND: Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs)
      have biological effects that could aggravate pulmonary emphysema. The aim of this
      study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats
      could induce and/or aggravate elastase-induced emphysema, and to investigate the
      underlying molecular mechanisms. METHODS: On day 1, Sprague-Dawley rats were
      intratracheally instilled with 25 U kg-1 pancreatic porcine elastase or saline.
      On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and
      500 MUg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals
      were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity,
      histological analysis of inflammation and emphysema, and lung mRNA expression of
      heme oxygenase-1 (HO-1), interleukin-1beta (IL-1beta), macrophage inflammatory
      protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1,
      and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed
      at the protein level by immunohistochemistry. RESULTS: TiO2 NPs per se did not
      modify the parameters investigated, but CB NPs increased
      perivascular/peribronchial infiltration, and macrophage MMP-12 expression,
      without inducing emphysema. Elastase administration increased BAL cellularity,
      histological inflammation, HO-1, IL-1beta and macrophage MMP-12 expression and
      induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to
      elastase, but exposure to CB NPs aggravated elastase-induced histological
      inflammation without aggravating emphysema. CONCLUSIONS: TiO2 and CB NPs did not
      aggravate elastase-induced emphysema. However, CB NPs induced histological
      inflammation and MMP-12 mRNA and protein expression in macrophages.

PMID- 22849373
TI  - Synergistic photothermal ablative effects of functionalizing carbon nanotubes
      with a POSS-PCU nanocomposite polymer.
AB  - BACKGROUND: The application of nanotechnology in biology and medicine represents
      a significant paradigm shift in the approach to the treatment of cancer. Evidence
      suggests that when exposed to near-infrared radiation (NIR), carbon nanotubes
      (CNTs) dissipate a substantial amount of heat energy. We have developed a novel
      nanocomposite polymer, polyhedral oligomeric silsesquioxane poly (carbonate-urea)
      urethane (POSS-PCU). POSS-PCU displays excellent biocompatibility and has been
      used in making artificial organs as well as protective coatings for medical
      devices. RESULTS: Functionalizing (or "coating") CNTs with POSS-PCU confers
      biocompatibility and increase the amount of heat energy generated, by enhancing
      dispersion. Here we demonstrate that POSS-PCU-functionalized multi-walled CNTs
      (MWNTs) act synergistically together when exposed to NIR to thermally ablate
      cancer cells. CONCLUSION: Given that POSS-PCU has already been used in human in
      first-in-man studies as trachea, lacrimal duct, bypass graft and other organs,
      our long-term goal is to take POSS-PCU coated CNTs to clinical studies to address
      the treatment of cancer by optimizing its therapeutic index and increasing its
      specificity via antibody conjugation.

PMID- 22849375
TI  - Breastfeeding among inner-city women: from intention before delivery to
      breastfeeding at hospital discharge.
AB  - OBJECTIVE: This study assessed the degree to which women's intention to
      breastfeed prior to delivery translates to actual breastfeeding at hospital
      discharge and to investigate predictors of breastfeeding in a minority inner-city
      population. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study
      of consecutive mother-infant dyads born July-September 2010 and discharged from
      the nursery at an academic community hospital in Philadelphia. RESULTS: The
      demographics of the 578 women who participated included a mean age of 25.3 years
      (SD 6.1), 61% African American and 18% Latina, 85% covered by Medicaid, and a
      mean postpartum hospital stay of 2.3 days. Overall, 60% expressed an intention to
      breastfeed prior to delivery (exclusively or with formula), but only 50% were
      breastfeeding at discharge. Of those who intended to breastfeed (exclusively or
      with formula), 75% were breastfeeding at discharge. Of those who intended to
      breastfeed exclusively, 40% were doing so at discharge. Of those who intended to
      bottle feed, 11% were breastfeeding at discharge. In multivariable analysis,
      older mothers and those with lower parity were more likely to breastfeed at
      discharge and also to breastfeed exclusively, controlling for ethnicity, parity,
      insurance, pregravida body mass index, score on the Edinburgh Postpartum
      Depression Scale, type of delivery, infant birth weight and gestational age.
      CONCLUSIONS: In a minority inner-city population, only three in four women who
      intended to breastfeed prior to delivery were breastfeeding at hospital
      discharge. However, one in 10 women previously not intending to breastfeed did
      so. Strategies are needed to promote and strengthen women's intention to
      breastfeed and to help women's breastfeeding outcomes meet their intentions.

PMID- 22849374
TI  - Applying 6-methylisoxanthopterin-enhanced fluorescence to examine protein-DNA
      interactions in the picomolar range.
AB  - Incorporation of fluorescent nucleoside analogues into duplex DNA usually leads
      to a reduction in quantum yield, which significantly limits their potential use
      and application. We have identified two pentamer DNA sequences containing 6
      methylisoxanthopterin (6-MI) (ATFAA and AAFTA, where F is 6-MI) that exhibit
      significant enhancement of fluorescence upon formation of duplex DNA with quantum
      yields close to that of monomeric 6-MI. The enhanced fluorescence dramatically
      increases the utility and sensitivity of the probe and is used to study protein
      DNA interactions of nanomolar specificity in this work. The increased sensitivity
      of 6-MI allows anisotropy binding measurements to be performed at DNA
      concentrations of 1 nM and fluorescence intensity measurements at 50 pM DNA. The
      ATFAA sequence was incorporated into DNA constructs to measure the binding
      affinity of four different protein-DNA interactions that exhibit sequence
      specific and non-sequence-specific recognition. In all cases, the K(d) values
      obtained were consistent with previously reported values measured by other
      methods. Time-resolved and steady-state fluorescence measurements demonstrate
      that 6-MI fluorescence is very sensitive to local distortion and reports on
      different degrees of protein-induced perturbations with single-base resolution,
      where the largest changes occur at the site of protein binding.

PMID- 22849376
TI  - Association of ALOX5AP gene single nucleotide polymorphisms and cerebral
      infarction in the Han population of northern China.
AB  - BACKGROUND: To explore the association of ALOX5AP single nucleotide polymorphisms
      (SNPs) and haplotype with the occurrence of cerebral infarction in the Han
      population of northern China. METHODS: Blood samples were collected from 236
      patients of Han ancestry with a history of cerebral infarction and 219 healthy
      subjects of Han ancestry with no history of cerebral infarction or cardiovascular
      disease. Applied Biosystems((r)) TaqMan((r)) SNP Genotyping Assays for SNP
      genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles
      (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and
      rs4147064). RESULTS: One SNP allele (A) of rs4073259 was significantly associated
      with development of cerebral infarction (P = 0.049). In comparison to control
      groups, haplotype rs9315050&rs9551963 AAAC [OR (95% CI) = 1.53 (1.02-2.29)], and
      genotypes rs4147064 CT [OR (95% CI) = 1.872 (1.082-3.241)], and rs9551963 AC [OR
      (95% CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in
      patients with hypertension. Genotype rs9579646 GG [OR (95% CI) = 2.926 (1.18
      7.251)] increased the risk of, while rs4073259 GG [OR (95% CI) = 0.381 (0.157
      0.922)] decreased the risk of cerebral infarction in patients with diabetes.
      CONCLUSION: These results suggest the ALOX5AP SNP A allele in rs4073259 and
      genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC
      were associated with an increased risk of ischemic stroke in the Han population,
      while rs4073259 GG was associated with a decreased risk.

PMID- 22849377
TI  - Localisation and role of activin receptor-interacting protein 1 in mouse brain.
AB  - Activin A, a stimulator of follicle-stimulating hormone secretion from the
      pituitary, acts as a neurotrophic and neuroprotective factor in the central
      nervous system. Activin receptor-interacting protein 1 (ARIP1) has been
      identified as a cytoplasmic protein that interacts with the type II receptor of
      activin (ActRII). However, the distribution pattern and function of ARIP1 are not
      well characterised in the brain. In the present study, we confirmed the existence
      of mRNA and protein of ARIP1 in the mouse brain, and found that ARIP1 was mainly
      localised at the hippocampus and hypothalamus in the cerebrum, granular layers in
      the cerebellum (especially in Purkinje cells of the cerebellum) and choroid
      epithelial cells by immunohistochemical staining. Furthermore, in contrast to the
      significant increase of activin A mRNA, ARIP1 mRNA and protein expression
      decreased in the mechanically lesioned brain of the mouse. Using neuroblastoma
      derived Neuro-2a cells to investigate the function of ARIP1, we found that
      overexpression of ARIP1 down-regulated the activin A-induced signal transduction
      and significantly decreased the voltage-gated Na(+)  current (I(Na) ). These data
      indicate that ARIP1 is a key molecule for the regulation of the action of activin
      in neurones, and also that decreased ARIP1 expression in the lesioned brain may
      be beneficial to the neurotrophic and neuroprotective roles of activin A in
      recovery after brain injury.

PMID- 22849378
TI  - Farnesyl diphosphate synthase, the target for nitrogen-containing bisphosphonate
      drugs, is a peroxisomal enzyme in the model system Dictyostelium discoideum.
AB  - NBP (nitrogen-containing bisphosphonate) drugs protect against excessive
      osteoclast-mediated bone resorption. After binding to bone mineral, they are
      taken up selectively by the osteoclasts and inhibit the essential enzyme FDPS
      (farnesyl diphosphate synthase). NBPs inhibit also growth of amoebae of
      Dictyostelium discoideum in which their target is again FDPS. A fusion protein
      between FDPS and GFP (green fluorescent protein) was found, in D. discoideum, to
      localize to peroxisomes and to confer resistance to the NBP alendronate. GFP was
      also directed to peroxisomes by a fragment of FDPS comprising amino acids 1-22.
      This contains a sequence of nine amino acids that closely resembles the
      nonapeptide PTS2 (peroxisomal targeting signal type 2): there is only a single
      amino acid mismatch between the two sequences. Mutation analysis confirmed that
      the atypical PTS2 directs FDPS into peroxisomes. Furthermore, expression of the
      D. discoideum FDPS-GFP fusion protein in strains of Saccharomyces cerevisiae
      defective in peroxisomal protein import demonstrated that import of FDPS into
      peroxisomes was blocked in a strain lacking the PTS2-dependent import pathway.
      The peroxisomal location of FDPS in D. discoideum indicates that NBPs have to
      cross the peroxisomal membrane before they can bind to their target.

PMID- 22849379
TI  - A cost-effectiveness analysis of dexamethasone versus prednisone in pediatric
      acute asthma exacerbations.
AB  - OBJECTIVES: The objective was to evaluate the cost-effectiveness of dexamethasone
      versus prednisone for the treatment of pediatric asthma exacerbations in the
      emergency department (ED). METHODS: This was a cost-effectiveness analysis using
      a decision analysis model to compare two oral steroid options for pediatric
      asthma patients: 5 days of oral prednisone and 2 days of oral dexamethasone (with
      two dispensing possibilities: either a prescription for the second dose or the
      second dose dispensed at the time of ED discharge). Using estimates from
      published studies for rates of prescription filling, compliance, and steroid
      efficacy, the projected rates of ED relapse visits, hospitalizations within 7 to
      10 days of the sentinel ED visit, direct costs, and indirect costs between the
      two arms were compared. RESULTS: The rate of return to the ED per 100 patients
      within 7 to 10 days of the sentinel ED visit for the prednisone arm was 12, for
      the dexamethasone/prescription arm was 10, and for the dexamethasone/dispense arm
      was 8. Rates of hospitalization per 100 patients were 2.8, 2.4, and 1.9,
      respectively. Direct costs per 100 patients for each arm were $20,500, $17,200,
      and $13,900, respectively. Including indirect costs related to missed parental
      work, total costs per 100 patients were $22,000, $18,500, and $15,000,
      respectively. Total cost savings per 100 patients for the
      dexamethasone/prescription arm compared to the prednisone arm was $3,500 and for
      the dexamethasone/dispense arm compared to the prednisone arm was $7,000.
      CONCLUSIONS: This decision analysis model illustrates that use of 2 days of
      dexamethasone instead of 5 days of prednisone at the time of ED visit for asthma
      leads to a decreased number of ED visits and hospital admissions within 7 to 10
      days of the sentinel ED visit and provides cost savings.

PMID- 22849380
TI  - Combined platelet count with sCD163 and genetic variants optimizes esophageal
      varices prediction in cirrhotic patients.
AB  - BACKGROUND AND AIM: Endoscopic screening for esophageal varices (EVs) is
      expensive and invasive. Besides traditional noninvasive markers, we explore
      additional candidate markers including portal hypertension serum marker-soluble
      CD136 (sCD163) and genetic variants of splanchnic vasodilatation and
      revascularization pathways for prediction of EVs in cirrhotic patients. METHODS:
      A total of 951 cirrhotic patients without history of variceal bleeding and an
      independent validation cirrhotic cohort were enrolled to evaluate the association
      between the presence of EVs and patients' clinical and genetic characteristics.
      RESULTS: Cirrhotic patients with EVs had higher serum sCD163 and heme oxygenase-1
      (HO-1) level, which was positively correlated with the number of risk alleles of
      HO-1 (S, A), vascular endothelial growth factor (VEGF [G, T]) and VEGF receptor-2
      (VEGFR2 [Ile]) genes, than those without EVs. Multivariate analysis showed that
      EVs in cirrhotic patients was predicted by low platelet count, high sCD163 level,
      splenomegaly, HO-1 AS and the VEGF GT risk haplotypes. Additive effects in
      relation to predict EVs were observed in the simultaneous presence of HO-1 AS and
      VEGF GT risk haplotypes. Combining low platelet count with high sCD163/risk
      haplotypes significantly increased the predictability of EVs. Furthermore,
      cirrhotic patients carrying both HO-1 AS and VEGF GT risk haplotypes had lower
      probability of being free of EVs bleeding compared to patients without above risk
      haplotypes. CONCLUSIONS: This study suggested that high sCD163 levels and genetic
      risk variants are additional markers that can be combined with low platelet count
      to optimize assessment of EVs and bleeding in cirrhotic patients.

PMID- 22849381
TI  - Re: laparoscopic anatrophic nephrolithotomy: developments of the technique in the
      era of minimally invasive surgery (from: Giedelman C, Arriaga J, Carmona O, et
      al. J Endourol 2012;26:444-450).

PMID- 22849382
TI  - The immunology of traumatic brain injury: a prime target for Alzheimer's disease
      prevention.
AB  - A global health problem, traumatic brain injury (TBI) is especially prevalent in
      the current era of ongoing world military conflicts. Its pathological hallmark is
      one or more primary injury foci, followed by a spread to initially normal brain
      areas via cascades of inflammatory cytokines and chemokines resulting in an
      amplification of the original tissue injury by microglia and other central
      nervous system immune cells. In some cases this may predispose individuals to
      later development of Alzheimer's disease (AD). The inflammatory-based progression
      of TBI has been shown to be active in humans for up to 17 years post TBI.
      Unfortunately, all neuroprotective drug trials have failed, and specific
      treatments remain less than efficacious. These poor results might be explained by
      too much of a scientific focus on neurons without addressing the functions of
      microglia in the brain, which are at the center of proinflammatory cytokine
      generation. To address this issue, we provide a survey of the TBI-related brain
      immunological mechanisms that may promote progression to AD. We discuss these
      immune and microglia-based inflammatory mechanisms involved in the progression of
      post-trauma brain damage to AD. Flavonoid-based strategies to oppose the antigen
      presenting cell-like inflammatory phenotype of microglia will also be reviewed.
      The goal is to provide a rationale for investigations of inflammatory response
      following TBI which may represent a pathological link to AD. In the end, a better
      understanding of neuroinflammation could open therapeutic avenues for abrogation
      of secondary cell death and behavioral symptoms that may mediate the progression
      of TBI to later AD.

PMID- 22849384
TI  - Exposure to predator odor and resulting anxiety enhances the expression of the
      alpha2 delta subunit of voltage-sensitive calcium channels in the amygdala.
AB  - The alpha2 delta subunit of voltage-sensitive calcium channels (VSCCs) is the
      molecular target of pregabalin and gabapentin, two drugs marked for the treatment
      of focal epilepsy, neuropathic pain, and anxiety disorders. Expression of the
      alpha2 delta subunit is up-regulated in the dorsal horns of the spinal cord in
      models of neuropathic pain, suggesting that plastic changes in the alpha2 delta
      subunit are associated with pathological states. Here, we examined the expression
      of the alpha2 delta-1 subunit in the amygdala, hippocampus, and frontal cortex in
      the trimethyltiazoline (TMT) mouse model of innate anxiety. TMT is a volatile
      molecule present in the feces of the rodent predator, red fox. Mice that show a
      high defensive behavior during TMT exposure developed anxiety-like behavior in
      the following 72 h, as shown by the light-dark test. Anxiety was associated with
      an increased expression of the alpha2 delta-1 subunit of VSCCs in the amygdaloid
      complex at all times following TMT exposure (4, 24, and 72 h). No changes in the
      alpha2 delta-1 protein levels were seen in the hippocampus and frontal cortex of
      mice exposed to TMT. Pregabalin (30 mg/kg, i.p.) reduced anxiety-like behavior in
      TMT-exposed mice, but not in control mice. These data offer the first
      demonstration that the alpha2 delta-1 subunit of VSCCs undergoes plastic changes
      in a model of innate anxiety, and supports the use of pregabalin as a disease
      dependent drug in the treatment of anxiety disorders.

PMID- 22849383
TI  - Induced and natural regulatory T cells in human cancer.
AB  - INTRODUCTION: Evidence suggests that FOXP3(+)CD25(high)CD4(+) regulatory T cells
      (Treg) which accumulate in cancer may have beneficial or unfavorable effects on
      prognosis. The presence in tumor-associated inflammatory infiltrates of two
      subsets of Treg with distinct phenotypic and functional profiles might explain
      these conflicting observations. AREAS COVERED: Human inducible (i) Treg arising
      by tumor-driven conversion of conventional CD4(+) T cells are highly suppressive,
      therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting
      tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral
      tolerance, control cancer-associated inflammation, which favors tumor
      progression. This division of labor between nTreg and iTreg is not absolute, and
      overlap may be common. Nevertheless, iTreg play a critical and major role in
      cancer and cancer therapy. The tumor microenvironment determines the type,
      frequency and suppression levels of accumulating Treg. EXPERT OPINION: In cancer,
      a selective removal or silencing of iTreg and not of nTreg should be a
      therapeutic goal. However, the implementation of this challenging strategy
      requires further studies of cellular and molecular crosstalk among immune cells
      in the tumor microenvironment.

PMID- 22849385
TI  - Concentration and temperature dependences of polyglutamine aggregation by
      multiscale coarse-graining molecular dynamics simulations.
AB  - The solvent-free multiscale coarse-graining model of polyglutamine was employed
      to study polyglutamine aggregation at different concentrations and temperatures
      by means of molecular dynamics simulation. The heterogeneity order parameter
      (HOP) was used to quantify the polyglutamine aggregation. Our simulation results
      demonstrate that polyglutamine aggregation is sensitive to concentration and
      temperature changes. In equilibrium states, polyglutamine molecules fluctuate
      between aggregating tightly and distributing uniformly. The degree of aggregation
      monotonically increases with decreasing temperature, but the fluctuation of HOP
      reaches its maximum at an intermediate temperature. With increasing
      concentration, the distribution of polyglutamines first changes from more uniform
      to more nonuniform and then changes back to be more uniform, and the HOP has the
      widest distribution at the turning point. Simulations with different system sizes
      indicate that the finite-size effect is trivial and do not change the conclusions
      drawn for the polyglutamine system. In addition, the composition of the potential
      energies has been analyzed to confirm that the nonbonded interactions dominate
      the aggregation of polyglutamines. These results can be thermodynamically
      understood by considering the competition between the system entropy and
      molecular interactions, and a statistical model based on HOP has been developed
      to explain the microscopic mechanism of polyglutamine aggregation. 

PMID- 22849386
TI  - Selective synthesis and device applications of semiconducting single-walled
      carbon nanotubes using isopropyl alcohol as feedstock.
AB  - The development of guided chemical vapor deposition (CVD) growth of single-walled
      carbon nanotubes provides a great platform for wafer-scale integration of aligned
      nanotubes into circuits and functional electronic systems. However, the
      coexistence of metallic and semiconducting nanotubes is still a major obstacle
      for the development of carbon-nanotube-based nanoelectronics. To address this
      problem, we have developed a method to obtain predominantly semiconducting
      nanotubes from direct CVD growth. By using isopropyl alcohol (IPA) as the carbon
      feedstock, a semiconducting nanotube purity of above 90% is achieved, which is
      unambiguously confirmed by both electrical and micro-Raman measurements. Mass
      spectrometric study was performed to elucidate the underlying chemical mechanism.
      Furthermore, high performance thin-film transistors with an on/off ratio above
      10(4) and mobility up to 116 cm(2)/(V.s) have been achieved using the IPA
      synthesized nanotube networks grown on silicon substrate. The method reported in
      this contribution is easy to operate and the results are highly reproducible.
      Therefore, such semiconducting predominated single-walled carbon nanotubes could
      serve as an important building block for future practical and scalable carbon
      nanotube electronics.

PMID- 22849387
TI  - Improving epidemic response: building bridges between the US and China.

PMID- 22849388
TI  - Fetal central nervous system injury in third trimester stillbirth: a
      clinicopathologic study of 63 cases.
AB  - We report the neuropathologic findings and clinicopathologic associations in 63
      3rd trimester singleton stillborn fetuses. All were >= 28 weeks estimated
      gestational age (EGA) with complete autopsies, including placental examination.
      Fetuses with chromosomal abnormalities, major congenital anomalies, and
      intrapartum demise were excluded. The cases were divided into those with
      abruption (n  =  12) and those with unexplained fetal demise (n  =  51). The
      latter group was then subdivided by gestational age with 3 subgroups (preterm 28
      to < 32 weeks EGA (n  =  16), preterm 32 to <37 weeks EGA (n  =  13), and term 37
      41 weeks EGA (n  =  22). Each group was further subdivided as appropriate-for
      gestational age/large-for-gestational age (AGA/LGA) or small-for-gestational age
      (SGA). Placental lesions were also evaluated and correlated with brain lesions.
      Established or recent injury involving gray or white matter was seen in 88% of
      the fetuses with unexplained demise versus 42% with abruption (P  =  0.001). The
      most common form of brain injury was established gray matter damage, seen in 65%
      of the fetuses with unexplained demise versus 25% with abruption (P  =  0.021),
      the most common pattern being established pontosubicular neuronal necrosis plus
      established neuronal necrosis in other sites. There was no significant difference
      in the frequency of brain injury between the SGA fetuses and AGA/LGA fetuses or
      between the unexplained stillbirth preterm and term subgroups, and there was no
      unequivocal correlation between placental lesions and brain lesions. Brain
      injury, most frequently established gray matter damage, is seen in the majority
      of stillborn infants with unexplained demise, indicating that the brain injury
      predates the period immediately before death.

PMID- 22849389
TI  - Sometimes when you hear hoof beats, it could be a zebra: consider the diagnosis
      of Fabry disease.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder that results
      from a deficiency of the enzyme alpha-galactosidase A. Fabry disease is present
      in 4-5% of men with unexplained left ventricular hypertrophy or cryptogenic
      stroke. As enzyme replacement therapy is now more widely available, it is
      important to recognise the signs and symptoms of the disease and establish the
      diagnosis so that early treatment can be started before irreversible organ damage
      occurs. CASE PRESENTATION: A previously fit and well 32-year-old Caucasian male
      presented with multisystem dysfunction including renal impairment. Although he
      had no suggestive symptoms, a diagnosis of Fabry disease was first established on
      a native renal biopsy. This was confirmed by enzymatic testing and subsequent
      genetic analysis that revealed a potentially new pathogenic variant. CONCLUSIONS:
      This case highlights the importance both of Fabry disease as a differential
      diagnosis in patients with renal impairment in the context of multi-system
      disease and also of adequate tissue sampling for electron microscopy when
      performing native renal biopsies.

PMID- 22849390
TI  - A Bayesian network approach to the database search problem in criminal
      proceedings.
AB  - BACKGROUND: The 'database search problem', that is, the strengthening of a case 
      in terms of probative value - against an individual who is found as a result of
      a database search, has been approached during the last two decades with
      substantial mathematical analyses, accompanied by lively debate and centrally
      opposing conclusions. This represents a challenging obstacle in teaching but also
      hinders a balanced and coherent discussion of the topic within the wider
      scientific and legal community. This paper revisits and tracks the associated
      mathematical analyses in terms of Bayesian networks. Their derivation and
      discussion for capturing probabilistic arguments that explain the database search
      problem are outlined in detail. The resulting Bayesian networks offer a distinct
      view on the main debated issues, along with further clarity. METHODS: As a
      general framework for representing and analyzing formal arguments in
      probabilistic reasoning about uncertain target propositions (that is, whether or
      not a given individual is the source of a crime stain), this paper relies on
      graphical probability models, in particular, Bayesian networks. This graphical
      probability modeling approach is used to capture, within a single model, a series
      of key variables, such as the number of individuals in a database, the size of
      the population of potential crime stain sources, and the rarity of the
      corresponding analytical characteristics in a relevant population. RESULTS: This
      paper demonstrates the feasibility of deriving Bayesian network structures for
      analyzing, representing, and tracking the database search problem. The output of
      the proposed models can be shown to agree with existing but exclusively formulaic
      approaches. CONCLUSIONS: The proposed Bayesian networks allow one to capture and
      analyze the currently most well-supported but reputedly counter-intuitive and
      difficult solution to the database search problem in a way that goes beyond the
      traditional, purely formulaic expressions. The method's graphical environment,
      along with its computational and probabilistic architectures, represents a rich
      package that offers analysts and discussants with additional modes of
      interaction, concise representation, and coherent communication.

PMID- 22849391
TI  - A creative approach to the development of an agenda for knowledge utilization:
      outputs from the 11th international knowledge utilization colloquium (KU 11).
AB  - A group of researchers and practitioners interested in advancing knowledge
      utilization met as a colloquium in Belfast (KU 11) and used a "world cafe"
      approach to exploit the social capital and shared understanding built up over
      previous events to consider the research and practice agenda. We considered three
      key areas of relevance to knowledge use: (1) understanding the nature of research
      use, influence and impact; (2) blended and collaborative approaches to knowledge
      production and use; and (3) supporting sustainability and spread of evidence
      informed innovations. The approach enabled the development of artifacts that
      reflected the three areas and these were analyzed using a creative hermeneutic
      approach. The themes that emerged and which are outlined in this commentary are
      not mutually exclusive. There was much overlap in the discussions and therefore
      of the themes, reflecting the complex nature of knowledge translation work. The
      agenda that has emerged from KU 11 also reflects the participatory and creative
      approach in which the meeting was structured and focused, and therefore
      emphasizes the processual, relational and contingent nature of some of the
      challenges we face. The past 20 years has seen an explosion in activity around
      understanding KU, and we have learned much about the difficulties. Whilst the
      agenda for the next decade may be becoming clearer, colloquia such as KU 11,
      using creative and engaging approaches, have a key role to play in dissecting,
      articulating and sharing that agenda. In this way, we also build an ever
      expanding international community that is dedicated to working towards increasing
      the chances of success for better patient care.

PMID- 22849392
TI  - A review of the health and economic implications of patent protection, with a
      specific focus on Thailand.
AB  - BACKGROUND: Although it has been two decades since the Thai Patent Act was
      amended to comply with the Agreement on Trade-Related Aspects of Intellectual
      Property Rights (TRIPS), there has been little emphasis given to assessing the
      implications of this amendment. The purpose of this review is to summarize the
      health and economic impact of patent protection, with a focus on the experience
      of Thailand. METHODS: A review of national and international empirical evidence
      on the health and economic implications of patents from 1980 to 2009 was
      undertaken. RESULTS: The findings illustrate the role of patent protection in
      four areas: price, present access, future access, and international trade and
      investment. Forty-three empirical studies were found, three of which were from
      Thai databases. Patenting does increase price, although the size of effect
      differs according to the methodology and country. Although weakening patent
      rights could increase present access, evidence suggests that strengthening
      patenting may benefit future access; although this is based on complex
      assumptions and estimations. Moreover, while patent protection appears to have a
      positive impact on trade flow, the implication for foreign direct investment
      (FDI) is equivocal. CONCLUSIONS: Empirical studies in Thailand, and other similar
      countries, are rare, compromising the robustness and generalizability of
      conclusions. However, evidence does suggest that patenting presents a significant
      inter-temporal challenge in balancing aspects of current versus future access to
      technologies. This underlines the urgent need to prioritize health research
      resources to assess the wider implications of patent protection.

PMID- 22849393
TI  - Electrostatic spin control in InAs/InP nanowire quantum dots.
AB  - Very robust voltage-controlled spin transitions in few-electron quantum dots are
      demonstrated. Two lateral-gate electrodes patterned on opposite sides of an
      InAs/InP nanowire are used to apply a transverse electric field and tune orbital
      energy separation down to level-pair degeneracy. Transport measurements in this
      regime allow us to demonstrate the breakdown of the standard alternate up/down
      spin filling scheme and unambiguously show singlet-triplet spin transitions. The
      strong confinement of the present devices leads to a large energy gain for the
      observed anomalous spin configurations that exceeds 4 meV. As a consequence, this
      behavior is well visible even at temperatures exceeding T = 20 K.

PMID- 22849394
TI  - Sensitive determination of cadmium in brown rice and spinach by flame atomic
      absorption spectrometry with solid-phase extraction.
AB  - A sensitive flame atomic absorption spectrometry (FAAS) method was developed for
      the determination of cadmium (Cd) in brown rice and spinach. The method involves
      extraction with 1 M hydrochloric acid (HCl), followed by a selective pre
      concentration by solid-phase extraction (SPE). The pH of the loading sample
      solution was adjusted to 4.0 for the brown rice and to 5.0 for the spinach. The
      masking agents, tartrate and citrate, were required for the spinach before pH
      adjustment. The SPE step achieved a 20-fold enrichment of the sample solution.
      The limits of quantification (LOQs) were 0.0054 mg kg-1 for the brown rice and
      0.0022 mg kg-1 for the spinach, being more sensitive than those of AOAC Official
      method 999.10. A single-laboratory validation was performed by testing spiked
      samples at 0.04 and 0.08 mg kg-1 for the brown rice, and 0.02 and 0.04 mg kg-1
      for the spinach. The average recoveries were 93.3-96.9% with relative standard
      deviations (RSDs) of 4.1-8.2% for brown rice, and 90.5-91.9% with RSDs of 5.8
      10.0% for spinach.

PMID- 22849395
TI  - Children younger than 7 years with type 1 diabetes are less physically active
      than healthy controls.
AB  - AIM: To examine if children younger than 7 years with type 1 diabetes are less
      physically active and spend more time sedentary than healthy children. METHODS:
      Using a repeated measures case-control study design, physical activity (PA) was
      measured by continuous combined accelerometer and heart rate registration for 7
      days at two time points during 1 year (autumn and spring). PA data were expressed
      as time spent sedentary, in moderate and vigorous intensity PA and total PA.
      Differences between groups and gender were analysed with mixed linear regression
      models. In this study there were 24 children (12 girls) with type 1 diabetes
      mellitus and 26 (14 girls) healthy controls, all younger than 7 years at
      inclusion. RESULTS: Children with diabetes were less active overall (p = 0.010)
      and spent 16 min less in moderate-to-vigorous PA (p = 0.006). The difference in
      sedentary time (21 min less) between groups was not significant (p = 0.21).
      Overall PA (12.1 counts/min per day, p = 0.004) and time in moderate and vigorous
      PA (16.0 min/day, p = 0.002) was significantly higher in boys than in girls. A
      significant effect of age was observed. CONCLUSION: Physical activity is
      significantly reduced in young children with type 1 diabetes.

PMID- 22849397
TI  - Oxidative coupling of indoles with ethyl 2-(disubstituted amino)acetates: an
      approach to achieve indolylglycine derivatives.
AB  - An efficient method for the synthesis of indolylglycine derivatives is described.
      The oxidative coupling reactions of ethyl 2-(disubstituted amino)acetates with
      indoles proceeded smoothly in the presence of meta-chloroperoxybenzoic acid
      (mCPBA) under ambient conditions to produce indolylglycine derivatives in
      satisfactory to excellent yields.

PMID- 22849396
TI  - Beyond differential expression: the quest for causal mutations and effector
      molecules.
AB  - High throughput gene expression technologies are a popular choice for researchers
      seeking molecular or systems-level explanations of biological phenomena.
      Nevertheless, there has been a groundswell of opinion that these approaches have
      not lived up to the hype because the interpretation of the data has lagged behind
      its generation. In our view a major problem has been an over-reliance on isolated
      lists of differentially expressed (DE) genes which - by simply comparing genes to
      themselves - have the pitfall of taking molecular information out of context.
      Numerous scientists have emphasised the need for better context. This can be
      achieved through holistic measurements of differential connectivity in addition
      to, or in replacement, of DE. However, many scientists continue to use isolated
      lists of DE genes as the major source of input data for common readily available
      analytical tools. Focussing this opinion article on our own research in skeletal
      muscle, we outline our resolutions to these problems - particularly a universally
      powerful way of quantifying differential connectivity. With a well designed
      experiment, it is now possible to use gene expression to identify causal
      mutations and the other major effector molecules with whom they cooperate,
      irrespective of whether they themselves are DE. We explain why, for various
      reasons, no other currently available experimental techniques or quantitative
      analyses are capable of reaching these conclusions.

PMID- 22849398
TI  - Factors influencing the length of the incision and the operating time for total
      thyroidectomy.
AB  - BACKGROUND: The incision used for thyroid surgery has become shorter over time,
      from the classical 10 cm long Kocher incision to the shortest 15 mm access
      achieved with Minimally Invasive Video-Assisted Thyroidectomy. This rather large
      interval encompasses many different possible technical choices, even if we just
      consider open surgery.The aim of the study was to assess the correlation between
      incision length and operation duration with a set of biometric and clinical
      factors and establish a rationale for the decision on the length of incision in
      open surgery. METHODS: Ninety-seven consecutive patients scheduled for total
      thyroidectomy were prospectively evaluated. All operations were performed by the
      same team and the surgeon decided the length of the incision according to his
      personal judgement. Patients who had previously undergone neck surgery were
      excluded. RESULTS: The length of the incision was strongly correlated with
      gender, thyroid volume, neck circumference and clinical diagnosis and weakly
      correlated with the body mass index. Operation duration was only weakly
      correlated with gender and neck circumference. Multiple linear regression
      revealed that the set of factors assessed explained almost 60 % of the variance
      in incision length but only 20 % of the variance in operation duration. When
      patients were classified according to the distribution of their thyroid volume,
      cases within one standard deviation of the mean did not show a significant
      difference in terms of operation duration with incisions of various lengths.
      CONCLUSIONS: Although thyroid volume was a major factor in driving the decision
      with respect to the length of the incision, our study shows that it had only
      minor effect on the duration of the operation. Many more open thyroidectomies
      could therefore be safely performed with shorter incisions, especially in women.
      Duration of the operation is probably more closely linked to the inherent
      technical difficulty of each case.

PMID- 22849399
TI  - Pragmatics in action: indirect requests engage theory of mind areas and the
      cortical motor network.
AB  - Research from the past decade has shown that understanding the meaning of words
      and utterances (i.e., abstracted symbols) engages the same systems we used to
      perceive and interact with the physical world in a content-specific manner. For
      example, understanding the word "grasp" elicits activation in the cortical motor
      network, that is, part of the neural substrate involved in planned and executing
      a grasping action. In the embodied literature, cortical motor activation during
      language comprehension is thought to reflect motor simulation underlying
      conceptual knowledge [note that outside the embodied framework, other
      explanations for the link between action and language are offered, e.g., Mahon,
      B. Z., & Caramazza, A. A critical look at the embodied cognition hypothesis and a
      new proposal for grouding conceptual content. Journal of Physiology, 102, 59-70,
      2008; Hagoort, P. On Broca, brain, and binding: A new framework. Trends in
      Cognitive Sciences, 9, 416-423, 2005]. Previous research has supported the view
      that the coupling between language and action is flexible, and reading an action
      related word form is not sufficient for cortical motor activation [Van Dam, W.
      O., van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied
      lexical-semantic representations. Human Brain Mapping, doi: 10.1002/hbm.21365,
      2011]. The current study goes one step further by addressing the necessity of
      action-related word forms for motor activation during language comprehension.
      Subjects listened to indirect requests (IRs) for action during an fMRI session.
      IRs for action are speech acts in which access to an action concept is required,
      although it is not explicitly encoded in the language. For example, the utterance
      "It is hot here!" in a room with a window is likely to be interpreted as a
      request to open the window. However, the same utterance in a desert will be
      interpreted as a statement. The results indicate (1) that comprehension of IR
      sentences activates cortical motor areas reliably more than comprehension of
      sentences devoid of any implicit motor information. This is true despite the fact
      that IR sentences contain no lexical reference to action. (2) Comprehension of IR
      sentences also reliably activates substantial portions of the theory of mind
      network, known to be involved in making inferences about mental states of others.
      The implications of these findings for embodied theories of language are
      discussed.

PMID- 22849400
TI  - Working memory capacity and visual-verbal cognitive load modulate auditory
      sensory gating in the brainstem: toward a unified view of attention.
AB  - Two fundamental research questions have driven attention research in the past:
      One concerns whether selection of relevant information among competing,
      irrelevant, information takes place at an early or at a late processing stage;
      the other concerns whether the capacity of attention is limited by a central,
      domain-general pool of resources or by independent, modality-specific pools. In
      this article, we contribute to these debates by showing that the auditory-evoked
      brainstem response (an early stage of auditory processing) to task-irrelevant
      sound decreases as a function of central working memory load (manipulated with a
      visual-verbal version of the n-back task). Furthermore, individual differences in
      central/domain-general working memory capacity modulated the magnitude of the
      auditory-evoked brainstem response, but only in the high working memory load
      condition. The results support a unified view of attention whereby the capacity
      of a late/central mechanism (working memory) modulates early precortical sensory
      processing.

PMID- 22849401
TI  - The contribution of primary and secondary somatosensory cortices to the
      representation of body parts and body sides: an fMRI adaptation study.
AB  - Although the somatosensory homunculus is a classically used description of the
      way somatosensory inputs are processed in the brain, the actual contributions of
      primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of
      touch remain poorly understood. We studied adaptation of the fMRI BOLD response
      in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the
      finger tips of the index and middle fingers. The first stimulus (adaptor) was
      delivered either to the index or to the middle finger of the right or left hand,
      and the second stimulus (test) was always administered to the left index finger.
      The overall BOLD response evoked by the stimulation was primarily contralateral
      in SI and was more bilateral in SII. However, our fMRI adaptation approach also
      revealed that both somatosensory cortices were sensitive to ipsilateral as well
      as to contralateral inputs. SI and SII adapted more after subsequent stimulation
      of homologous as compared with nonhomologous fingers, showing a distinction
      between different fingers. Most importantly, for both somatosensory cortices,
      this finger-specific adaptation occurred irrespective of whether the tactile
      stimulus was delivered to the same or to different hands. This result implies
      integration of contralateral and ipsilateral somatosensory inputs in SI as well
      as in SII. Our findings suggest that SI is more than a simple relay for sensory
      information and that both SI and SII contribute to the spatial coding of touch by
      discriminating between body parts (fingers) and by integrating the somatosensory
      input from the two sides of the body (hands).

PMID- 22849402
TI  - Process and domain specificity in regions engaged for face processing: an fMRI
      study of perceptual differentiation.
AB  - The degree to which face-specific brain regions are specialized for different
      kinds of perceptual processing is debated. This study parametrically varied
      demands on featural, first-order configural, or second-order configural
      processing of faces and houses in a perceptual matching task to determine the
      extent to which the process of perceptual differentiation was selective for faces
      regardless of processing type (domain-specific account), specialized for specific
      types of perceptual processing regardless of category (process-specific account),
      engaged in category-optimized processing (i.e., configural face processing or
      featural house processing), or reflected generalized perceptual differentiation
      (i.e., differentiation that crosses category and processing type boundaries).
      ROIs were identified in a separate localizer run or with a similarity regressor
      in the face-matching runs. The predominant principle accounting for fMRI signal
      modulation in most regions was generalized perceptual differentiation. Nearly all
      regions showed perceptual differentiation for both faces and houses for more than
      one processing type, even if the region was identified as face-preferential in
      the localizer run. Consistent with process specificity, some regions showed
      perceptual differentiation for first-order processing of faces and houses (right
      fusiform face area and occipito-temporal cortex and right lateral occipital
      complex), but not for featural or second-order processing. Somewhat consistent
      with domain specificity, the right inferior frontal gyrus showed perceptual
      differentiation only for faces in the featural matching task. The present
      findings demonstrate that the majority of regions involved in perceptual
      differentiation of faces are also involved in differentiation of other visually
      homogenous categories.

PMID- 22849404
TI  - Inhibition of return impairs phosphene detection.
AB  - Efficient visual exploration requires the ability to select possible target
      locations via spatial attention and to deselect previously inspected locations
      via inhibition of return (IOR). Although a great deal is known about the effects
      of spatial attention on processing in visual cortex, much less is known about the
      effects of IOR on early visual areas. One possibility is that IOR acts in an
      opposite way to spatial attention, such that, whereas spatial attention enhances
      target related neural signals in visual cortex, IOR suppress target-related
      signals. Using a novel dual-coil TMS protocol, we found that IOR reduced the
      probability of detecting a TMS-induced phosphene in extrastriate cortex (V5).
      Specifically, a nonpredictive spatial precue presented 500 or 800 msec before
      stimulation significantly reduced the probability of detecting a phosphene when
      the precue appeared contralaterally to the site of stimulation (i.e.,
      ipsilaterally to the potential location of the phosphene), compared with
      ipsilaterally or centrally presented cues. This result demonstrates that IOR
      facilitates visual exploration by directly affecting the strength of target
      related signals in extrastriate visual cortex. This result is consistent with
      neurophysiological models of attention, which postulate that IOR modulates
      perception by biasing competition between sensory representations.

PMID- 22849403
TI  - The effect of aging on the neural correlates of phonological word retrieval.
AB  - Age has a differential effect on cognition, with word retrieval being one of the
      cognitive domains most affected by aging. This study examined the functional and
      structural neural correlates of phonological word retrieval in younger and older
      adults using word and picture rhyme judgment tasks. Although the behavioral
      performance in the fMRI task was similar for the two age groups, the older adults
      had increased activation in the right pars triangularis across tasks and in the
      right pars orbitalis for the word task only. Increased activation together with
      preserved performance in the older participants would suggest that increased
      activation was related to compensatory processing. We validated this hypothesis
      by showing that right pars triangularis activation during correct rhyme judgments
      was highest in participants who made overall more errors, therefore being most
      error-prone. Our findings demonstrate that the effect of aging differ in adjacent
      but distinct right inferior frontal regions. The differential effect of age on
      word and picture tasks also provides new clues to the level of processing that is
      most affected by age in speech production tasks. Specifically, we suggest that
      right inferior frontal activation in older participants is needed to inhibit
      errors.

PMID- 22849405
TI  - Neurodynamics of cognitive set shifting in monkey frontal cortex and its causal
      impact on behavioral flexibility.
AB  - Flexible behavior depends on the ability to shift an internal cognitive set as
      soon as external demand changes. According to neuropsychological studies in human
      and nonhuman primates, selective lesion to the PFC impairs flexible behavioral
      shifting. Our previous fMRI study demonstrated that the prefrontal regions showed
      transient activation related to set shifting in humans and monkeys. To
      investigate the underlying neural processing, we recorded single-unit activities
      while monkeys performed a cognitive-set-shifting task, which required shifting
      between shape-matching and color-matching behaviors. We identified a group of
      neurons in the inferior arcuate region that exhibited selective activity when the
      monkeys were required to shift their cognitive set. These shift-related neurons
      were localized in the focal area along the posterior bank of the inferior arcuate
      sulcus. Reversible inactivation of this area ipsilateral to the response hand
      with a small volume of muscimol (even with 0.5 MUl) selectively impaired the
      performance of behavioral shifting. Moreover, this selective behavioral
      impairment strongly correlated with the dose of muscimol. These results
      demonstrated localized neural processing for cognitive set shifting and its
      causal role for behavioral flexibility in primates.

PMID- 22849407
TI  - Hsp90 rescues PTK6 from proteasomal degradation in breast cancer cells.
AB  - PTK6 [protein tyrosine kinase 6; also known as Brk (breast tumour kinase)] is a
      non-receptor tyrosine kinase, closely related to Src, but evolutionarily
      distinct, that is up-regulated in various cancers, including breast cancer. Hsp90
      (heat-shock protein 90) was identified as a PTK6-interacting protein in HEK
      (human embryonic kidney)-293 cells overexpressing PTK6. Hsp90 interacted with the
      PTK6 tyrosine kinase catalytic domain, but catalytic activity was not required
      for the interaction. Geldanamycin, an Hsp90 inhibitor, significantly decreased
      the PTK6 protein level through proteasome-dependent degradation, but did not
      affect the level of Src. Geldanamycin treatment also decreased phosphorylation of
      PTK6 substrates due to reduced amounts of PTK6. Moreover, overexpression of CHIP
      [C-terminus of Hsc70 (heat-shock cognate 70)-interacting protein], a chaperone
      dependent E3 ligase, enhanced proteosomal degradation of PTK6. Geldanamycin
      increased the interaction of PTK6 with CHIP, but decreased the interaction of
      PTK6 with Hsp90. We also found that endogenous PTK6 associated with Hsp90 and
      geldanamycin decreased expression of endogenous PTK6 in breast carcinoma cells.
      Finally, we report that silencing endogenous CHIP expression in breast carcinoma
      cells inhibited geldanamycin-induced PTK6 reduction. These results demonstrate
      that Hsp90 plays an essential role in regulating PTK6 stability and suggest that
      Hsp90 inhibitors may be useful as therapeutic drugs for PTK6-positive cancers,
      including breast cancer.

PMID- 22849406
TI  - Characterization of the interactions of mammalian RNA polymerase I associated
      proteins PAF53 and PAF49.
AB  - Masami Muramatsu's laboratory demonstrated the critical role of RNA polymerase I
      (Pol I)-associated factor PAF53 in mammalian rRNA transcription. They have also
      identified a second polymerase associated factor, PAF49. Both PAF49 and PAF53
      copurify with that fraction of the RNA polymerase I molecules that can function
      in transcription initiation in vitro. PAF49 and PAF53 are the mammalian
      homologues of two subunits of yeast RNA polymerase I, A34.5 and A49, that form a
      TFIIF-related subcomplex in yeast RNA polymerase I. In light of those
      publications, we investigated the interactions between various deletion and
      substitution mutants of mammalian PAF49 and PAF53 with the purpose of identifying
      those domains of the mammalian proteins that interact. Comparison of our results
      with structural studies on yeast A34.5 and A49 demonstrates that the yeast and
      mammalian proteins may in fact share structural similarities. In fact, the
      deletion mutagenesis data confirmed and extended the structural studies. For
      example, amino acids 41-86 of PAF49 were sufficient to provide the basis for
      heterodimerization. In silico structural analysis predicted that this region
      could assume a structure similar to the homologous region of yeast A34.5. Those
      similarities are insufficient, by themselves, for the proteins to form
      interspecific heterodimers. However, substitution of amino acids 52-98 of yeast
      A34.5 with amino acids 41-86 of mammalian PAF49 resulted in a protein that could
      heterodimerize with mouse PAF53.

PMID- 22849408
TI  - Phytochrome B inhibits binding of phytochrome-interacting factors to their target
      promoters.
AB  - Phytochromes are red and far-red light receptors in plants that mediate critical
      responses to light throughout the lifecycle. They achieve this in part by
      targeting negatively acting bHLH transcription factors called phytochrome
      interacting factors (PIFs) for degradation within the nucleus. However, it is not
      known whether protein degradation is the primary mechanism by which phytochromes
      inhibit these repressors of photomorphogenesis. Here, we use chromatin
      immunoprecipitation to show that phyB inhibits the regulatory activity of PIF1
      and PIF3 by releasing them from their DNA targets. The N-terminal fragment of
      phyB (NG-GUS-NLS; NGB) also inhibits binding of PIF3 to its target promoters.
      However, unlike full-length phyB, NGB does not promote PIF3 degradation,
      establishing the activity of NGB reflects its ability to inhibit PIF binding to
      DNA. We further show that Pfr forms of both full-length phyB and NGB inhibit DNA
      binding of PIF1 and PIF3 in vitro. Taken together, our results indicate that phyB
      inhibition of PIF function involves two separate processes: sequestration and
      protein degradation.

PMID- 22849409
TI  - Preoperative use of romiplostim in thrombocytopenic patients with chronic
      hepatitis C and liver cirrhosis.
AB  - BACKGROUND AND AIM: Patients infected with hepatitis C virus (HCV) often develop
      chronic liver disease, liver cirrhosis and concurrent thrombocytopenia, which
      manifests as decreased platelet counts and bleeding complications. Romiplostim, a
      thrombopoietin mimetic peptibody that stimulates the thrombopoietin receptor, has
      been used as a treatment for primary immune thrombocytopenia. We monitored the
      efficacy of preoperative romiplostim over 90 days in 35 male patients with
      chronic hepatitis C, liver cirrhosis and thrombocytopenia secondary to HCV
      infection. METHODS: Romiplostim was administered at 2 MUg/kg Q1W for a maximum of
      one month with a target platelet count of 70 * 10(9)/L as a prerequisite for
      planned surgeries. Bone marrow aspirate was collected at baseline and at the end
      of the study, along with liver and kidney function assessments. A complete blood
      count was performed every third day throughout the study period. RESULTS: A rapid
      response to romiplostim therapy was observed, with 33/35 patients achieving
      platelet counts >= 70 * 10(9)/L and thereby eligible for surgery. An initial mean
      platelet count of 31 * 10(9)/L increased to a maximum peak range of 73-240 *
      10(9)/L, occurring between days 18 and 39. The reticulin bone marrow grade
      remained negative in all patients. Surgical interventions were associated with no
      postoperative bleeding or thrombotic complications. CONCLUSIONS: Preoperative
      romiplostim administration may represent a viable alternative to increase
      platelet counts to a level acceptable for elective surgical interventions in
      patients with chronic liver disease and severe thrombocytopenia secondary to HCV
      infection who are unresponsive to standard therapy. Further studies in larger
      numbers of patients and over a longer period of time are warranted.

PMID- 22849410
TI  - Characterization of the electron- and photon-driven plasmonic excitations of
      metal nanorods.
AB  - A computational analysis of the electron- and photon-driven surface-plasmon
      resonances of monomer and dimer metal nanorods is presented to elucidate the
      differences and similarities between the two excitation mechanisms in a system
      with well-understood optical properties. By correlating the nanostructure's
      simulated electron energy-loss spectrum and loss-probability maps with its
      induced polarization and scattered electric field we discern how certain plasmon
      modes are selectively excited and how they funnel energy from the excitation
      source into the near- and far-field. Using a fully retarded electron-scattering
      theory capable of describing arbitrary three-dimensional nanoparticle geometries,
      aggregation schemes, and material compositions, we find that electron energy-loss
      spectroscopy (EELS) is able to indirectly probe the same electromagnetic hot
      spots that are generated by an optical excitation source. Comparison with recent
      experiment is made to verify our findings.

PMID- 22849411
TI  - Predictors of eyewitness identification decisions from video lineups in England:
      a field study.
AB  - Eyewitness identification decisions from 1,039 real lineups in England were
      analysed. Identification procedures have undergone dramatic change in the United
      Kingdom over recent years. Video lineups are now standard procedure, in which
      each lineup member is seen sequentially. The whole lineup is seen twice before
      the witness can make a decision, and the witness can request additional viewings
      of the lineup. A key aim of this paper was to investigate the association between
      repeated viewing and eyewitness decisions. Repeated viewing was strongly
      associated with increased filler identification rates, suggesting that witnesses
      who requested additional viewings were more willing to guess. In addition,
      several other factors were associated with lineup outcomes, including the age
      difference between the suspect and the witness, the type of crime committed, and
      delay. Overall, the suspect identification rate was 39%, the filler
      identification rate was 26% and the lineup rejection rate was 35%.

PMID- 22849412
TI  - If anything else comes to mind...better keep it to yourself? Delayed recall is
      discrediting--unjustifiably.
AB  - Inconsistencies in eyewitness accounts are perceived as indicative of inaccuracy
      and reduce the witnesses' credibility. Reminiscence, the delayed recall of
      previously not recalled information, is generally interpreted as a type of
      inconsistency. Even though it does not necessarily involve the falsity of the
      statements, reminiscence presents a counterintuitive instance with mostly unknown
      reliability. Two studies empirically assessed the accuracy of reminiscent items
      after retention intervals of up to 1 week and contrasted them with peoples'
      beliefs regarding their accuracy. In line with an implicit assumption of memory
      fading with the passage of time, delayed recall of previously unmentioned details
      was judged to be unreliable. In contrast, actual accuracy of reminiscent details
      was consistently high and even comparable to immediate recollections. Although
      participants generally underestimated accuracy, it was most pronounced in the
      case of reminiscence. The findings are discussed within the context of
      contemporary legal practice, such as jury instructions.

PMID- 22849413
TI  - You have the right to understand: the deleterious effect of stress on suspects'
      ability to comprehend Miranda.
AB  - Miranda v. Arizona (384 U.S. 436, 1966) required that suspects be explicitly
      warned of the right to avoid self-incrimination and the right to legal
      representation. This research was designed to examine whether stress, induced via
      an accusation of wrong-doing, undermined or enhanced suspects' ability to
      comprehend their Miranda rights. Participants were randomly assigned to either be
      accused (n = 15) or not accused (n = 15) of having cheated on an experimental
      task in a two-cell between-subjects experimental design. Results supported the
      hypothesis that stress undermines suspects' ability to comprehend their Miranda
      rights. Participants who were accused of cheating exhibited significantly lower
      levels of Miranda comprehension than participants who were not accused of
      cheating. The theoretical processes responsible for these effects and the
      implications of the findings for police interrogation are discussed.

PMID- 22849414
TI  - Mental sets in conduct problem youth with psychopathic features: entity versus
      incremental theories of intelligence.
AB  - The purpose of the current study was to examine the effect of a motivational
      intervention on conduct problem youth with psychopathic features. Specifically,
      the current study examined conduct problem youths' mental set (or theory)
      regarding intelligence (entity vs. incremental) upon task performance. We
      assessed 36 juvenile offenders with psychopathic features and tested whether
      providing them with two different messages regarding intelligence would affect
      their functioning on a task related to academic performance. The study employed a
      MANOVA design with two motivational conditions and three outcomes including
      fluency, flexibility, and originality. Results showed that youth with
      psychopathic features who were given a message that intelligence grows over time,
      were more fluent and flexible than youth who were informed that intelligence is
      static. There were no significant differences between the groups in terms of
      originality. The implications of these findings are discussed including the
      possible benefits of interventions for adolescent offenders with conduct problems
      and psychopathic features.

PMID- 22849415
TI  - Blind consent? A social psychological investigation of non-readership of click
      through agreements.
AB  - Across two studies we aimed to measure empirically the extent of non-readership
      of click-through agreements (CTAs), identify the dominant beliefs about CTAs
      contributing to non-readership, and experimentally manipulate these beliefs to
      decrease automatic non-reading behavior and enhance contract efficiency. In our
      initial questionnaire study (Study 1), as predicted, the vast majority of
      participants reported not reading CTAs and the most prevalent beliefs about CTAs
      contributing to non-readership included: they are too long and time-consuming,
      they are all the same, they give one no choice but to agree, they are irrelevant,
      and vendors are generally reputable. Manipulating these beliefs on a simulated
      music website (Study 2) revealed an increase in readership. In addition, CTA
      comprehension and CTA rejection rates were both increased significantly by
      manipulating the length of the CTA. These results demonstrate support for the
      influence of widely held beliefs about CTAs on contract readership, provide
      evidence against the common "limited cognition" perspective on non-readership,
      and suggest that presenting CTAs in a short, readable format can increase CTA
      readership and comprehension as well as shopping of CTA terms.

PMID- 22849416
TI  - Blind lineup administration as a prophylactic against the postidentification
      feedback effect.
AB  - Confidence and other testimony-relevant judgments may be distorted when witnesses
      are given confirming postidentification feedback, and double-blind procedures
      wherein the lineup administrator does not know the identity of the suspect-are a
      commonly proposed, but untested, remedy for this effect. In the current study,
      mock witnesses viewed a staged crime video followed by a target-present or target
      absent lineup where the administrator was or was not presumed to know the
      identity of the suspect. After making an identification decision, witnesses were
      or were not given realistic, but nonidentification-specific, feedback, and then
      confidence and other judgments were assessed. A significant interaction was found
      between blind condition and feedback such that feedback inflated confidence and
      other judgments in presumed nonblind conditions only; feedback had no effect on
      participants in presumed blind conditions. As predicted by the selective cue
      integration framework-a theoretical model suggested to explain the interaction
      between presumed blind administration and feedback-this interaction was
      significant only for inaccurate participants. These results suggest that blind
      administration may serve as a prophylactic against the negative effects of
      postidentification feedback. In addition, the effectiveness of our subtle
      feedback in influencing judgments suggests that lineup administrators should take
      care not to provide any feedback to eyewitnesses.

PMID- 22849417
TI  - Online solicitation offenders are different from child pornography offenders and
      lower risk contact sexual offenders.
AB  - The current study compared 38 lower risk (based on actuarial risk assessments)
      men convicted of contact sexual offenses against children, 38 child pornography
      offenders, and 70 solicitation offenders (also known as luring or traveler
      offenders). Solicitation and child pornography offenders were better educated
      than contact offenders but did not differ on other sociodemographic variables. In
      comparison to child pornography offenders, solicitation offenders had lower
      capacity for relationship stability and lower levels of sex drive/preoccupation
      and deviant sexual preference. Solicitation offenders were also more problematic
      than lower risk contact offenders on sex drive/preoccupation and capacity for
      relationship stability and had greater self-reported use of child pornography.
      Differences between groups on two actuarial risk measures, the Static-99 and the
      VASOR, were inconsistent. This study suggests that solicitation offenders differ
      in meaningful ways from lower risk contact offenders and child pornography
      offenders and, consequently, in risk, treatment, and supervision needs.

PMID- 22849418
TI  - Short and long-term prediction of recidivism using the youth level of
      service/case management inventory in a sample of serious young offenders.
AB  - The present investigation examined the predictive accuracy of the Youth Level of
      Service/Case Management Inventory (YLS/CMI) for youth and adult recidivism in a
      Canadian sample of 167 youths (93 males, 74 females) charged with serious
      offenses who received psychological services from a community mental health
      outpatient clinic. Youths were followed for an average of 7 years in the
      community, and predictive accuracy was examined for several recidivism outcomes
      as a function of gender, ethnicity, and developmental age group. YLS/CMI total
      scores significantly predicted all recidivism categories in the overall sample
      (area under the curve values ranged from 0.66 to 0.77) although the instrument as
      a whole, and its criminogenic needs, demonstrated somewhat stronger and more
      consistent predictive accuracy for youth outcomes. The YLS/CMI also demonstrated
      significant predictive accuracy within demographic subgroups. The implications of
      these findings are discussed in terms of the use of risk-need assessment tools in
      providing clinical assessment, treatment, and case management services to diverse
      young offender groups.

PMID- 22849419
TI  - Subgroup differences and implications for contemporary risk-need assessment with
      juvenile offenders.
AB  - Risk-need assessment is widely accepted as best practice with juvenile offenders
      and is underpinned by a healthy research literature on risk assessment
      inventories. Previous studies have found both similarities and differences on
      risk measures when gender and racial/ethnic subgroups have been compared.
      Differential validity has been examined, but differential prediction has been
      overlooked. The current study undertook gender and ethnic comparisons for a large
      sample (n = 3568) of community-based juvenile offenders who were evaluated using
      the Australian Adaptation of the Youth Level of Service/Case Management Inventory
      (YLS/CMI-AA). Analyses showed various gender and ethnic differences at the item
      level, across domain scores and on the total inventory score, but not for
      validity indices. However, 1-year reoffending rates for youth in three
      classification categories (low, moderate, high) varied by gender and ethnicity.
      The findings were related to contemporary understandings of the risk factors for
      offending and the dynamics of crime for gender/ethnic subgroups. It is argued
      that in spite of these subgroup differences, a generic inventory such as the
      YLS/CMI-AA can be used fairly with various subgroups. Recommendations for how
      this could be accomplished are provided.

PMID- 22849420
TI  - Community violence to prison assault: a test of the behavioral continuity
      hypothesis.
AB  - This large-scale study (N = 23,277) investigated the relationship between
      criminal history in the community and serious or assaultive prison misconduct,
      while controlling for the effects of inmate characteristics, general criminality,
      and custody level. Community violence variables included the rate of prior
      violent crime arrests and the types of prior violent crime, as well as a range of
      specific violent crimes of conviction. Behavioral continuity from community to
      prison was neither simple nor intuitively discernible, depending on the type,
      recency, and pattern of community criminality. Application of logistic regression
      models revealed that the omnibus measure of the rate of prior violent arrests was
      not related to either serious or assaultive prison misconduct. Prior arrests for
      assault and current convictions for robbery and/or assault, but not prior or
      current homicides, were associated with an increased risk for prison violence.
      Current conviction for a sexual assault had the strongest inverse relationship to
      prison violence, while prior arrests for sexual assault showed no relationship to
      prison violence. A more "nuanced" approach in assigning risk ratings based on
      prior criminal history and seriousness of offense is recommended.

PMID- 22849421
TI  - Institutional delivery service utilization and associated factors among mothers
      who gave birth in the last 12 months in Sekela District, north west of Ethiopia:
      a community-based cross sectional study.
AB  - BACKGROUND: Reduction of maternal mortality is a global priority particularly in
      developing countries including Ethiopia where maternal mortality ratio is one of
      the highest in the world. The key to reducing maternal mortality ratio and
      improving maternal health is increasing attendance by skilled health personnel
      throughout pregnancy and delivery. However, delivery service is significantly
      lower in Amhara Regional State, Ethiopia. Therefore, this study aimed to assess
      factors affecting institutional delivery service utilization among mothers who
      gave birth in the last 12 months in Sekela District, Amhara Region, Ethiopia.
      METHODS: Community-based cross-sectional study was conducted among mothers with
      birth in the last 12 months during August, 2010. Multistage sampling technique
      was used to select 371 participants. A pre tested and structured questionnaire
      was used to collect data. Bivariate and multivariate data analysis was performed
      using SPSS version 16.0 software. RESULTS: The study indicated that 12.1% of the
      mothers delivered in health facilities. Of 87.9% mothers who gave birth at home,
      80.0% of them were assisted by family members and relatives. The common reasons
      for home delivery were closer attention from family members and relatives
      (60.9%), home delivery is usual practice (57.7%), unexpected labour (33.4%), not
      being sick or no problem at the time of delivery (21.6%) and family influence
      (14.4%). Being urban resident (AOR [95% CI] = 4.6 [1.91, 10.9]), ANC visit during
      last pregnancy (AOR [95% CI] = 4.26 [1.1, 16.4]), maternal education level (AOR
      [95%CI] =11.98 [3.36, 41.4]) and knowledge of mothers on pregnancy and delivery
      services (AOR [95% CI] = 2.97[1.1, 8.6]) had significant associations with
      institutional delivery service utilization. CONCLUSIONS: Very low institutional
      delivery service utilization was observed in the study area. Majority of the
      births at home were assisted by family members and relatives. ANC visit and lack
      of knowledge on pregnancy and delivery services were found to be associated with
      delivery service utilization. Strategies with focus on increasing ANC uptake and
      building knowledge of the mothers and their partners would help to increase
      utilization of the service. Training and assigning skilled attendants at Health
      Posta level to provide skilled home delivery would improve utilization of the
      service.

PMID- 22849422
TI  - Bromobenzene flame retardants in the Great Lakes atmosphere.
AB  - Seven bromobenzene flame retardants were measured in vapor-phase samples
      collected at five sites, all near the shores of the North American Great Lakes
      during 2008-2009, inclusive. The target compounds were hexabromobenzene (HBB),
      pentabromobenzene (PBBz), pentabromotoluene (PBT), pentabromobenzylacrylate
      (PBBA), pentabromobenzyl bromide (PBBB), tetrabromo-p-xylene (pTBX), and
      pentabromoethyl benzene (PBEB). Detection frequencies were, on average, higher
      than 50% for all of the compounds, with the exception of PBBA, which was detected
      only in 22% of all the samples. Considering all the sampling sites together, HBB
      showed the highest average concentration (4.6 +/- 1.0 pg/m(3)), followed by PBBB
      (3.3 +/- 0.5 pg/m(3)) and PBEB (1.0 +/- 0.1 pg/m(3)). The concentrations of these
      compounds were generally significantly correlated with one another, with the
      exception of PBBA, which was correlated only to PBBB. The atmospheric
      concentrations of PBT, pTBX, PBBB, and PBBA tracked local human population
      density, suggesting that these compounds are or were used in a variety of
      commercial products. Unexpectedly, the concentration of PBEB was highest at the
      remote site of Eagle Harbor in northern Michigan, whereas that of HBB was highest
      at Sturgeon Point, ~25 km southwest of Buffalo, New York. The lack of dependence
      of these two compounds' concentrations on human population suggests local point
      sources.

PMID- 22849423
TI  - Update on gene and stem cell therapy approaches for spinal muscular atrophy.
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) is the leading genetic cause of
      pediatric death to which at present there is no effective therapeutic. The
      genetic defect is well characterized as a mutation in exon 7 of the survival of
      motor neuron (SMN) gene. The current gene therapy approach focuses on two main
      methodologies, the replacement of SMN1 or augmentation of SMN2 readthrough. The
      most promising of the current work focuses on the delivery of SMN via AAV9
      vectors via intravenous delivery. AREAS COVERED: In the review the authors
      examine the current research in the field of stem cell and gene therapy
      approaches for SMA. Also focusing on delivery methods, timing of administration
      and general caveats that must be considered with translational work for SMA.
      EXPERT OPINION: Gene therapy currently offers the most promising avenue of
      research for a successful therapeutic for SMA. There are many important practical
      and ethical considerations which must be carefully considered when dealing with
      clinical trial in infants such as the invasiveness of the surgery, the correct
      patient cohort and the potential risks.

PMID- 22849424
TI  - Dietary total antioxidant capacity and the occurrence of metabolic syndrome and
      its components after a 3-year follow-up in adults: Tehran Lipid and Glucose
      Study.
AB  - BACKGROUND: There is growing evidence that dietary antioxidants could have
      favorable effects on the attenuation and prevention of metabolic disorders. In
      the current study we investigated the association of dietary total antioxidant
      capacity (TAC) and metabolic syndrome (MetS) components and the occurrence of the
      MetS during a 3-year follow-up. METHODS: This longitudinal study was conducted in
      the framework of Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011,
      on 1983 adults, aged 19-70 y. The usual intakes of participant were measured
      using a validated semi-quantitative food frequency questionnaire and dietary TAC
      was estimated at baseline. The MetS components were assessed at baseline and 3
      years later. Multiple logistic regression models were used to estimate the
      occurrence of the MetS and its components according to dietary TAC quartile
      categories. RESULTS: The mean age of participants was 40.4 +/- 13.0 y, and mean
      BMI was 27.03 +/- 4.9 kg/m2 at baseline. After adjustment for potential
      confounding variables, TAC was associated with MetS components at baseline.
      Participant with highest TAC score had lower weight and abdominal fat gain during
      the 3 year follow-up. The chance of having the MetS, abdominal obesity and
      hypertension after 3 years decreased across the increasing dietary TAC quartile
      (P for trend < 0.01). Dietary TAC more than 1080 MUmolTE/100 g of food, resulted
      in a 38% decrease in the risk of central obesity (OR = 0.62, 95% CI = 0.38-0.99).
      CONCLUSION: We demonstrated that higher dietary antioxidant intakes have
      favorable effects on metabolic disorders and, more interestingly, prevent
      subsequent weight and abdominal fat gain during a 3-year follow-up.

PMID- 22849425
TI  - Epineurial adipocytes are dispensable for Schwann cell myelination.
AB  - Previous clinical observations and data from mouse models with defects in lipid
      metabolism suggested that epineurial adipocytes may play a role in peripheral
      nervous system myelination. We have used adipocyte-specific Lpin1 knockout mice
      to characterize the consequences of the presence of impaired epineurial
      adipocytes on the myelinating peripheral nerve. Our data revealed that the
      capacity of Schwann cells to establish myelin, and the functional properties of
      peripheral nerves, were not affected by compromised epineurial adipocytes in
      adipocyte-specific Lpin1 knockout mice. To evaluate the possibility that Lpin1
      negative adipocytes are still able to support endoneurial Schwann cells, we also
      characterized sciatic nerves from mice carrying epiblast-specific deletion of
      peroxisome proliferator-activated receptor gamma, which develop general
      lipoatrophy. Interestingly, even the complete loss of adipocytes in the
      epineurium of peroxisome proliferator-activated receptor gamma knockout mice did
      not lead to detectable defects in Schwann cell myelination. However, probably as
      a consequence of their hyperglycemia, these mice have reduced nerve conduction
      velocity, thus mimicking the phenotype observed under diabetic condition.
      Together, our data indicate that while adipocytes, as regulators of lipid and
      glucose homeostasis, play a role in nerve function, their presence in epineurium
      is not essential for establishment or maintenance of proper myelin.

PMID- 22849426
TI  - Synthetic studies on furanosteroids: construction of the viridin core structure
      via Diels-Alder/retro-Diels-Alder and vinylogous Mukaiyama aldol-type reaction.
AB  - The synthesis of the viridin class of furanosteroids core skeleton from the
      readily available 2,3-dihydro-4-hydroxyinden-1-one (6) is described. Our strategy
      was broken down into three parts: (1) Synthesis of functionalized alkyne oxazoles
      of type 5; (2) intramolecular Diels-Alder/retro-Diels-Alder reaction of 5
      followed by tautomerization and elaboration of R to give silylated
      furanonaphthols 4 bearing an aldehyde side chain; and (3) annulation of ring A by
      intramolecular vinylogous Mukaiyama aldol-type cyclization. Two major challenges
      were faced in the last step: (i) furanonaphthol derivatives bearing a beta
      hydroxyaldehyde functionality (R(1) = OH) suffered from dehydration to the E
      enal, which is geometrically incapable of cyclization, and (ii) the functionality
      at C17 had a strong influence on the conversion of 4 to 3, as exemplified by the
      failure of the free ketone (X = O) or its derivatives (X = H, OH; X = H, OAc) to
      cyclize. In the end, success was realized with the analogous C17-norketone (X =
      H, H).

PMID- 22849428
TI  - Iloperidone, asenapine and lurasidone: a primer on their current status.
AB  - INTRODUCTION: Three newer atypical antipsychotic drugs were FDA-approved in 2009
      and 2010 in the following order: iloperidone, asenapine and lurasidone. The three
      drugs are indicated for the treatment of acute schizophrenia. Asenapine is also
      approved for treatment of manic or mixed episodes associated with bipolar I
      disorder, for the maintenance treatment of schizophrenia and as an adjunctive
      therapy with lithium or valproate for the acute treatment of manic or mixed
      episodes associated with bipolar I disorder in adults. AREAS COVERED: This review
      compares and contrasts the current preclinical, clinical, safety and tolerability
      profiles of the three newer drugs, as reported in published preclinical and
      clinical studies, product labels, poster presentations and press releases. EXPERT
      OPINION: Preclinical studies have reported that the three drugs have variable
      affinities for a wide range of neurotransmitter receptors, and are active in
      animal models predictive of antipsychotic activity. Asenapine is the first
      antipsychotic to be administered sublingually, whereas iloperidone requires
      titration to minimize orthostatic hypotension. Asenapine and lurasidone are
      associated with dose-related akathisia, whereas iloperidone is not. The three
      drugs appear to have relatively benign metabolic profiles. The availability of
      the three novel antipsychotics should provide additional options for improved
      treatment of schizophrenia and other psychotic disorders.

PMID- 22849430
TI  - Statistical methods for identifying differentially expressed genes in RNA-Seq
      experiments.
AB  - RNA sequencing (RNA-Seq) is rapidly replacing microarrays for profiling gene
      expression with much improved accuracy and sensitivity. One of the most common
      questions in a typical gene profiling experiment is how to identify a set of
      transcripts that are differentially expressed between different experimental
      conditions. Some of the statistical methods developed for microarray data
      analysis can be applied to RNA-Seq data with or without modifications. Recently
      several additional methods have been developed specifically for RNA-Seq data
      sets. This review attempts to give an in-depth review of these statistical
      methods, with the goal of providing a comprehensive guide when choosing
      appropriate metrics for RNA-Seq statistical analyses.

PMID- 22849431
TI  - Microheterogeneity in native and cation-exchanged Nafion membranes.
AB  - 2-(4'-Pyridyl)benzimidazole (4PBI) has been used to investigate the
      microheterogeneity of water nanochannels of Nafion membranes at two different
      hydration levels. Native as well as cation-exchanged Nafion membranes are found
      to protonate one of the two monoprotonated forms of 4PBI selectively. In native
      membranes and in those in which H(3)O(+) ions are replaced by (CH(3))(4)N(+)
      ions, the pyridyl nitrogen is protonated preferentially. In Na(+)-exchanged
      membranes, however, the benzimidazole nitrogen is protonated selectively. Unlike
      other fluorescent probes used in earlier studies, 4PBI can differentiate between
      the two different cation-exchanged membranes at lower as well as higher hydration
      levels.

PMID- 22849427
TI  - Neurometabolite effects of response to quetiapine and placebo in adolescents with
      bipolar depression.
AB  - OBJECTIVE: Mood stabilizers have been reported to affect brain concentrations of
      myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of
      quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and
      potential predictors of response to QUET in adolescents with bipolar depression.
      METHODS: Twenty-six adolescents with bipolar depression participated in an 8-week
      placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline
      and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and
      4T at two sites, with 8 cm(3) voxels placed in the right and left dorsolateral
      prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used
      to calculate absolute concentrations of NAA and mI. RESULTS: Twenty-six subjects
      had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these
      subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo
      (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS]
      score). Although baseline ACC mI did not predict responder status, responders had
      significantly lower posttreatment ACC mI values than did nonresponders (3.27+/
      .71 vs. 4.23+/-.70; p=0.004). There were no significant differences in the
      changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group
      (ACC: -0.55+/-1.3 vs.+0.25+/-1.5, p=0.23; right-DLPFC: -0.55+/-1.3 vs. 0.33+/
      0.89, p=0.13; left-DLPFC: -0.04+/-0.91 vs.+0.29+/-0.61, p=0.41). CONCLUSION: We
      found that posttreatment, not baseline, ACC mI levels were associated with
      response to QUET in adolescents with bipolar depression. There were no
      differences in NAA concentration changes between the QUET and PBO groups. Larger
      studies including different brain regions would help to clarify the effects of
      QUET on neurochemistry in patients with bipolar disorder.

PMID- 22849432
TI  - Hole surface trapping in CdSe nanocrystals: dynamics, rate fluctuations, and
      implications for blinking.
AB  - Carrier trapping is one of the main sources of performance degradation in
      nanocrystal-based devices. Yet the dynamics of this process is still unclear. We
      present a comprehensive investigation into the efficiency of hole transfer to a
      variety of trap sites located on the surface of the core or the shell or at the
      core/shell interface in CdSe nanocrystals with both organic and inorganic
      passivation, using the atomistic semiempirical pseudopotential approach. We
      separate the contribution of coupling strength and energetics in different
      systems and trap configurations, obtaining useful general guidelines for trapping
      rate engineering. We find that trapping can be extremely efficient in core-only
      systems, with trapping times orders of magnitude faster than radiative
      recombination. The presence of an inorganic shell can instead bring the trapping
      rates well below the typical radiative recombination rates observed in these
      systems.

PMID- 22849434
TI  - Physicians in private practice: reasons for being a social franchise member.
AB  - BACKGROUND: Evidence is emerging on the cost-effectiveness, quality and health
      coverage of social franchises. But little is known about the motivations of
      providers to join or remain within a social franchise network, or the impact that
      franchise membership has on client volumes or revenue earnings. METHODS: (i)
      Uncontrolled facility based of a random sample of 230 franchise members to assess
      self-reported motivations; (ii) A 24 month prospective cohort study of 3 cohorts
      of physicians who had been in the franchise for 4 years, 2 years and new members
      to track monthly case load and revenue generated. RESULTS: The most common
      reasons for joining the franchise were access to high quality and cheap drugs
      (96.1%) and feelings of social responsibility, (95.2%). The effects of joining
      the franchise on the volume of family planning services is shown in the 2009
      cohort where the average monthly service volume increased from 18.5 per physician
      to 70.6 per physician during their first 2 years in the franchise, (p<0.01).
      These gains are sustained during the 3rd and 4th year of franchise membership, as
      the 2007 cohort reported increases of monthly average family planning service
      volume from 71.2 per physician to 102.8 per physician (p<0.01). The net income of
      cohort 2009 increased significantly (p=0.024) during their first two years in the
      franchise. The results for cohorts 2007 and 2005 also show a generalized trend in
      increasing income. CONCLUSIONS: The findings show how franchise membership
      impacts the volume of franchise and non-franchised services. The increases in
      client volumes translated directly into increases in earnings among the franchise
      members, an unanticipated effect for providers who joined in order to better
      serve the poor. This finding has implications for the social franchise business
      model that relies upon subsidized medical products to reduce financial barriers
      for the poor. The increases in out of pocket payments for health care services
      that were not price controlled by the franchise is a concern. As the field of
      social franchises continues to mature its business models towards more
      sustainable and cost recovery management practices, attention should be given
      towards avoiding commercialization of services.

PMID- 22849433
TI  - Selective extracellular vesicle-mediated export of an overlapping set of
      microRNAs from multiple cell types.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small RNA molecules that regulate
      expression of specific mRNA targets. They can be released from cells, often
      encapsulated within extracellular vesicles (EVs), and therefore have the
      potential to mediate intercellular communication. It has been suggested that
      certain miRNAs may be selectively exported, although the mechanism has yet to be
      identified. Manipulation of the miRNA content of EVs will be important for future
      therapeutic applications. We therefore wished to assess which endogenous miRNAs
      are enriched in EVs and how effectively an overexpressed miRNA would be exported.
      RESULTS: Small RNA libraries from HEK293T cells and vesicles before or after
      transfection with a vector for miR-146a overexpression were analysed by deep
      sequencing. A subset of miRNAs was found to be enriched in EVs; pathway analysis
      of their predicted target genes suggests a potential role in regulation of
      endocytosis. RT-qPCR in additional cell types and analysis of publicly available
      data revealed that many of these miRNAs tend to be widely preferentially
      exported. Whilst overexpressed miR-146a was highly enriched both in transfected
      cells and their EVs, the cellular:EV ratios of endogenous miRNAs were not grossly
      altered. MiR-451 was consistently the most highly exported miRNA in many
      different cell types. Intriguingly, Argonaute2 (Ago2) is required for miR-451
      maturation and knock out of Ago2 has been shown to decrease expression of other
      preferentially exported miRNAs (eg miR-150 and miR-142-3p). CONCLUSION: The
      global expression data provided by deep sequencing confirms that specific miRNAs
      are enriched in EVs released by HEK293T cells. Observation of similar patterns in
      a range of cell types suggests that a common mechanism for selective miRNA export
      may exist.

PMID- 22849435
TI  - Mapping the N-glycome of human von Willebrand factor.
AB  - vWF (von Willebrand factor) is a key component for maintenance of normal
      haemostasis, acting as the carrier protein of the coagulant Factor VIII and
      mediating platelet adhesion at sites of vascular injury. There is ample evidence
      that vWF glycan moieties are crucial determinants of its expression and function.
      Of particular clinical interest, ABH antigens influence vWF plasma levels
      according to the blood group of individuals, although the molecular mechanism
      underlying this phenomenon remains incompletely understood. The present paper
      reports analyses of the human plasma vWF N-glycan population using advanced MS.
      Glycomics analyses revealed approximately 100 distinct N-glycan compositions and
      identified a variety of structural features, including lactosaminic extensions,
      ABH antigens and sulfated antennae, as well as bisecting and terminal GlcNAc
      residues. We estimate that some 300 N-glycan structures are carried by human vWF.
      Glycoproteomics analyses mapped ten of the consensus sites known to carry N
      glycans. Glycan populations were found to be distinct, although many structural
      features were shared across all sites. Notably, the H antigen is not restricted
      to particular N-glycosylation sites. Also, the Asn(2635) site, previously
      designated as unoccupied, was found to be highly glycosylated. The delineation of
      such varied glycan populations in conjunction with current models explaining vWF
      activity will facilitate research aimed at providing a better understanding of
      the influence of glycosylation on vWF function.

PMID- 22849436
TI  - Biodiversity inventories and conservation of the marine fishes of Bootless Bay,
      Papua New Guinea.
AB  - BACKGROUND: The effective management and conservation of biodiversity is
      predicated on clearly defined conservation targets. Species number is frequently
      used as a metric for conservation prioritization and monitoring changes in
      ecosystem health. We conducted a series of synoptic surveys focusing on the
      fishes of the Bootless Bay region of Papua New Guinea to generate a checklist of
      fishes of the region. Bootless Bay lies directly south of Port Moresby, the
      capital of Papua New Guinea, and experiences the highest human population density
      of any marine area in the country. Our checklist will set a baseline against
      which future environmental changes can be tracked. RESULTS: We generated a
      checklist of 488 fish species in 72 families found in Bootless Bay during a two
      week sampling effort. Using incident-based methods of species estimation, we
      extrapolate there to be approximately 940 fish species in Bootless Bay, one of
      the lowest reported numbers in Papua New Guinea. CONCLUSIONS: Our data suggest
      that the Bootless Bay ecosystem of Papua New Guinea, while diverse in absolute
      terms, has lower fish biodiversity compared to other shallow marine areas within
      the country. These differences in faunal diversity are most likely a combination
      of unequal sampling effort as well as biophysical factors within Bootless Bay
      compounded by historical and/or contemporary anthropogenic disturbances.

PMID- 22849437
TI  - Forgiveness, depressive symptoms, and communication at the end of life: a study
      with family members of hospice patients.
AB  - INTRODUCTION: Forgiveness has begun to receive empirical attention in end-of-life
      contexts, but primarily among patients. This study examined forgiveness issues
      and communication priorities among family members of hospice patients. METHODS:
      Surveys were distributed to family members of home-care patients in a large not
      for-profit hospice in the Great Lakes region of the United States. Family members
      wrote what they would like to say to patients before they died. They also rated
      the importance of several expressions (love, gratitude, giving and seeking
      forgiveness, saying farewell) and the extent to which they had already expressed
      these messages. Participants rated their depressive symptoms and the quantity of
      unresolved offenses committed by themselves and the patient. RESULTS: Of 147
      surveys returned by participants, 142 were usable. In comparison with forgiveness
      related communications, expressions of love, gratitude, and farewell were more
      consistently rated important; yet many participants rated forgiveness (giving and
      seeking) as extremely important. If forgiveness was rated important but had not
      been fully expressed, participants reported more depressive symptoms (p<0.05).
      Also, unresolved offenses (by participants or patients) correlated positively
      with depressive symptoms (p<0.05). CONCLUSION: Although not as commonly endorsed
      as expressions of love and gratitude, forgiveness-related communications are seen
      as extremely important by many family members of hospice patients. If family
      members see forgiveness (granting or seeking) as important but have not completed
      the process, these unresolved issues are associated with depressive symptoms.
      This study suggests that unresolved offenses and forgiveness issues warrant
      assessment and clinical attention within families receiving hospice care.

PMID- 22849438
TI  - Screen time is more strongly associated than physical activity with overweight
      and obesity in 9- to 16-year-old Australians.
AB  - BACKGROUND: Both reduced moderate-to-vigorous physical activity (MVPA) and
      increased screen time have been implicated in the aetiology of childhood
      overweight/obesity. This study aimed to determine which behaviour had the
      stronger association with overweight/obesity. METHOD: 2200 randomly selected 9-
      to 16-year-old Australians provided four 24-h use-of-time recalls. Participants
      were classified into weight status categories and as high or low physical active,
      and high or low screen time according to Australian guidelines (>=60 min MVPA;
      <=120 min recreational screen time daily). Multivariate logistic regression was
      used to calculate the odds ratios (OR) for overweight/obesity for each screen
      time and MVPA category. RESULTS: Increased likelihood of overweight or obese was
      often associated with high screen time (ORs, 2.13-2.55 for boys and 1.47-1.72 for
      girls), but only sometimes and less strongly associated with low MVPA (ORs, 0.49
      2.55 for boys and 1.06-1.47 for girls). Analyses conducted for combined screen
      time and MVPA categories showed screen time to be a stronger indicator of weight
      status than physical activity, especially in boys. CONCLUSION: Overweight and
      obesity were more strongly associated with screen time than physical activity.
      Screen time may be an important target for interventions aimed at reducing
      childhood overweight and obesity.

PMID- 22849439
TI  - Hypoglycaemic effect of Melothria heterophylla in streptozotocin-induced diabetic
      rats.
AB  - CONTEXT: In the Indian traditional system of medicine, Melothria heterophylla
      (Lour.) Cogn., (Cucurbitaceae) is prescribed for the treatment of diabetes
      mellitus. OBJECTIVE: In the present study, the antidiabetic effect of ethanol
      extract of Melothria heterophylla (EEMH), and its active isolated constituents
      were investigated in streptozotocin (STZ)-induced diabetic Swiss albino rats.
      METHOD: Successive Soxhlet extraction of the dried total aerial parts with
      petroleum ether for defatting and then with ethanol (95%) to obtain ethanol
      extract, which was concentrated under reduced pressure. Hyperglycemia was induced
      in rats by STZ (50 mg/kg, body weight). Twenty-four hours after STZ induction,
      respective groups of diabetic rats received EEMH (200 and 400 mg/kg, body
      weight), gallic acid (GA) (2 and 4 mg/kg, body weight), and rutin (RU) (2 and 4
      mg/kg, body weight), respectively, orally daily for 15 days. Glibenclamide (0.5
      mg/kg, orally) served as reference. Blood glucose levels and change in body
      weight were measured on every 5(th) day during 15 days of treatment. Biochemical
      parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic
      pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and serum insulin, were
      measured. RESULTS: EEMH and its active constituents significantly (p < 0.01)
      normalized blood glucose levels and serum biochemical parameters as compared to
      those of STZ controls. Both GA (4 mg/kg) and RU (4 mg/kg) exhibited maximum
      glucose lowering effect (69.1 and 66.7%, respectively) in diabetic rats compared
      to the other dose (2 mg/kg) at the end of the study. EEMH, gallic acid and RU
      also showed significant increase in serum insulin, and body weight of STZ-induced
      diabetic rats. CONCLUSION: Therefore, ethanol extract of Melothria heterophylla,
      GA and RU demonstrated remarkable antidiabetic activity in STZ-induced diabetic
      rats.

PMID- 22849440
TI  - A range-wide genetic bottleneck overwhelms contemporary landscape factors and
      local abundance in shaping genetic patterns of an alpine butterfly (Lepidoptera:
      Pieridae: Colias behrii).
AB  - Spatial and environmental heterogeneity are major factors in structuring species
      distributions in alpine landscapes. These landscapes have also been affected by
      glacial advances and retreats, causing alpine taxa to undergo range shifts and
      demographic changes. These nonequilibrium population dynamics have the potential
      to obscure the effects of environmental factors on the distribution of genetic
      variation. Here, we investigate how demographic change and environmental factors
      influence genetic variation in the alpine butterfly Colias behrii. Data from 14
      microsatellite loci provide evidence of bottlenecks in all population samples. We
      test several alternative models of demography using approximate Bayesian
      computation (ABC), with the results favouring a model in which a recent
      bottleneck precedes rapid population growth. Applying independent calibrations to
      microsatellite loci and a nuclear gene, we estimate that this bottleneck affected
      both northern and southern populations 531-281 years ago, coinciding with a
      period of global cooling. Using regression approaches, we attempt to separate the
      effects of population structure, geographical distance and landscape on patterns
      of population genetic differentiation. Only 40% of the variation in F(ST) is
      explained by these models, with geographical distance and least-cost distance
      among meadow patches selected as the best predictors. Various measures of genetic
      diversity within populations are also decoupled from estimates of local abundance
      and habitat patch characteristics. Our results demonstrate that demographic
      change can have a disproportionate influence on genetic diversity in alpine
      species, contrasting with other studies that suggest landscape features control
      contemporary demographic processes in high-elevation environments.

PMID- 22849441
TI  - Triple-phase abdominal computed tomography for detecting spontaneous
      portopulmonary shunts in cirrhotic patients.
AB  - BACKGROUND AND AIM: Data on prevalence of portopulmonary shunts (PPS) are quite
      limited. Most studies have used cineportography or echocardiography for
      diagnosis. Only few recent case reports have reported the use of computed
      tomography (CT) for identification of PPS. This study tried to determine the
      prevalence of PPS in patients with cirrhosis using contrast-enhanced CT of the
      abdomen, and to determine their association with demographic and clinical
      characteristics. METHODS: A total of 150 subjects with cirrhosis who had
      previously undergone triple-phase CT were analyzed. PPS was diagnosed when at
      least one esophageal varix met all of the following criteria: (i) it could be
      followed cephalad into the chest to the level of the inferior pulmonary vein or
      left atrium; (ii) it abutted the wall of either of these structures; (iii) it had
      luminal continuity with one of these structures; and (iv) it was no longer seen
      one slice above the level of contact. RESULTS: Of 150 subjects, 18 were excluded
      for incomplete data. The prevalence of PPS was found to be 26/132 (19.7%). Of
      these, 14 (53.8%) patients had PPS draining into the left atrium and 12 (46.2%)
      had those draining into one of the pulmonary veins. Presence of PPS was
      associated with the presence of varices at endoscopy, ascites, thrombocytopenia
      and splenomegaly. CONCLUSION: In our study, the largest study on PPS to date, the
      prevalence of PPS in cirrhotic patients using triple phase CT was found to be
      19.7%. CT may be a useful technique to study PPS and their clinical implications.

PMID- 22849442
TI  - Mechanisms involved in cellular ceramide homeostasis.
AB  - Sphingolipids are ubiquitous and critical components of biological membranes.
      Their biosynthesis starts with soluble precursors in the endoplasmic reticulum
      and culminates in the Golgi complex and plasma membrane. Ceramides are important
      intermediates in the biosynthesis of sphingolipids, such as sphingomyelin, and
      their overload in the membranes is injurious to cells. The major product of
      ceramide metabolism is sphingomyelin. We observed that sphingomyelin synthase
      (SMS) 1 or SMS2 deficiencies significantly decreased plasma and liver
      sphingomyelin levels. However, SMS2 but not SMS1 deficiency increased plasma
      ceramides. Surprisingly, SMS1 deficiency significantly increased glucosylceramide
      and ganglioside GM3, but SMS2 deficiency did not. To explain these unexpected
      findings about modest to no significant changes in ceramides and increases in
      other sphingolipids after the ablation of SMS1, we hypothesize that cells have
      evolved several organelle specific mechanisms to maintain ceramide homeostasis.
      First, ceramides in the endoplasmic reticulum membranes are controlled by its
      export to Golgi by protein mediated transfer. Second, in the Golgi, ceramide
      levels are modulated by their enzymatic conversion to different sphingolipids
      such as sphingomyelin, and glucosylceramides. Additionally, these sphingolipids
      can become part of triglyceride-rich apolipoprotein B-containing lipoproteins and
      be secreted. Third, in the plasma membrane ceramide levels are maintained by
      ceramide/sphingomyelin cycle, delivery to lysosomes, and efflux to extracellular
      plasma acceptors. All these pathways might have evolved to ensure steady cellular
      ceramide levels.

PMID- 22849493
TI  - Endoscopic biliary sphincterotomy dilation.

PMID- 22849492
TI  - Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F
      actin.
AB  - The Abl family nonreceptor tyrosine kinase Arg/Abl2 interacts with cortactin, an
      Arp2/3 complex activator, to promote actin-driven cell edge protrusion. Both Arg
      and cortactin bind directly to filamentous actin (F-actin). While protein-protein
      interactions between Arg and cortactin have well-characterized downstream effects
      on the actin cytoskeleton, it is unclear whether and how Arg and cortactin affect
      each other's actin binding properties. We employ actin cosedimentation assays to
      show that Arg increases the stoichiometry of binding of cortactin to F-actin at
      saturation. Using a series of Arg deletion mutants and fragments, we demonstrate
      that the Arg C-terminal calponin homology domain is necessary and sufficient to
      increase the stoichiometry of binding of cortactin to F-actin. We also show that
      interactions between Arg and cortactin are required for optimal affinity between
      cortactin and the actin filament. Our data suggest a mechanism for Arg-dependent
      stimulation of binding of cortactin to F-actin, which may facilitate the
      recruitment of cortactin to sites of local actin network assembly.

PMID- 22849494
TI  - Missed opportunities in early diagnosis of symptomatic colorectal cancer.
AB  - OBJECTIVE: delays in diagnosis of symptomatic colorectal cancer are a reality in
      our context. This study aims at identifying missed diagnostic opportunities,
      describing events, clinical clues and most common mistakes, and quantifying
      delays. MATERIAL AND METHODS: an observational descriptive study was performed in
      order to review all case histories. Two experts reviewed the case histories of
      all the patients from the 4th Catchment Area of Asturias diagnosed with
      colorectal cancer in 2009. All data were analysed using bivariate and
      multivariate logistic regression. RESULTS: full information on 119 patients out
      of 143 patients was collected. 34.45% had a clinical missed opportunity 
      confidence interval (CI) 95%: 30.92-39.68-. Outcomes show an average of 2.41
      missed opportunities and 2.61 diagnostic clinical clues per patient. The number
      of patients with missed opportunities was significantly higher. The total amount
      of co-morbidities was higher in patients with missed opportunities (2.7). This
      was the main determinant. The main diagnostic key was iron-deficiency anaemia
      (46.3%). It produced the longest delay (300 days). Not having requested
      diagnostic tests was the most common mistake (43.3%). Having at least one missed
      opportunity entailed an average delay of 235.8 days between the first visit to
      the office and the referral to a consultant. CONCLUSIONS: in clinical practice,
      missed opportunities to start a diagnostic assessment in patients with
      presumptive diagnosis of colorectal cancer are common. The most significant
      clinical clue and the one generating the longest delay is iron-deficiency
      anaemia. The diagnostic delay is important and is caused mainly by not
      identifying symptoms.

PMID- 22849495
TI  - Protective ileostomy: complications and mortality associated with its closure.
AB  - INTRODUCTION: diverting loop ileostomies are widely used in colorectal surgery to
      protect low rectal anastomoses. However, they may have various complications,
      among which are those associated with the subsequent stoma closure. The present
      study analyses our experience in a series of patients undergoing closure of loop
      ileostomies. METHOD: retrospective study of all the patients undergoing ileostomy
      closure at our hospital between 2006-2010. There were 89 patients: 56 males (63%)
      and 33 females (37%) with a mean age of 55 (38-71) years. The most common
      indication for ileostomy was protection of a low rectal anastomosis, 81 patients
      (91%). The waiting time until stoma closure, type and frequency of the
      complications, length of hospital stay and mortality rate are analysed. RESULTS:
      waiting time before surgery was 8 (1-25) months. Forty-one patients (45,9%)
      developed some type of complication, three were reoperated (3.37%) and one
      patient died (1.12%). The most important complications were intestinal
      obstruction (32.6%), diarrhoea(6%), surgical wound infection (6%),
      enterocutaneous fistula (4.5%), rectorrhagia (3.4%) and anastomotic leak (1.12%).
      The mean length of patient stay was 7.54 (2-23) days. CONCLUSIONS: protective
      ostomies in low rectal anastomoses have proved to be the only preventive measure
      for reducing the morbidity and mortality rates for anastomotic leakage. However,
      creation means subsequent closure, which must not be considered a minor procedure
      but an operation with possibly significant complications, including death, as has
      been shown in publications on the subject and in our own series.

PMID- 22849496
TI  - Safety and efficacy of large balloon sphincteroplasty in a third care hospital.
AB  - BACKGROUND AND AIMS: large balloon sphincteroplasty (LBS) associated with
      sphincterotomy (ES) has gained acceptance as a useful tool in extracting
      difficult bile duct stones. Our purpose was to evaluate the efficacy and safety
      of LBS with balloons > or = 10 mm in clinical practice setting. PATIENTS AND
      METHODS: unicentre prospective study in a tertiary care hospital. All patients
      who underwent LBS associated with ES between July 2007 and March 2011 were
      included prospectively in a database recording clinical aspects, procedure data,
      outcome and complications.Success is the main outcome defined as complete stone
      removal documented by absence of any filling defect during a final occlusion
      cholangiogram and absence of clinical or radiological findings after the ERCP
      consistent with remaining stones. Complications as pancreatitis, cholangitis,
      post-ERCP bleeding, perforation and others were also measured. RESULTS: one
      hundred twenty procedures were made in 109 patients with balloons ranging from 10
      to 20 mm. Success rate was 91% in the first attempt and 96.7% after two
      procedures. Mechanical lithotripsy was only needed in one case (0.8%).
      Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk
      patients. CONCLUSION: large balloon sphincteroplasty associated to sphincterotomy
      in clinical practice is a very effective and safe technique.

PMID- 22849497
TI  - Patterns of extension of gastrointestinal stromal tumors (GIST) treated with
      imatinib (Gleevec(r)) by 18F-FDG PET/CT.
AB  - BACKGROUND AND AIM: currently it is recognized the usefulness of 18F-FDG PET in
      assessing response to therapy with imatinib (Gleevec(r)) in the gastrointestinal
      tract sarcomas (GIST). To facilitate the follow-up of these studies is important
      to know the patterns of metastatic spread. The aim of this paper is to describe
      patterns observed in the 18F-FDG PET/CT. METHOD: retrospective study included 29
      patients who underwent 18F-FDG PET/CT after being diagnosed with unresectable or
      metastatic GIST. In total, 87 PET/CT studies were performed (1-6 controls per
      patient) with a mean time of follow-up 6-36 months. We analyzed the location of
      the lesions evidenced in PET, CT and fusion. Images were evaluated visually and
      semiquantitatively (SUV). In cases in which has been considered necessary,
      additional images have been undertaken: PET delayed imaging, intravenous contrast
      CT and inspiratory chest CT. RESULTS: the most common primary site was the
      stomach (41%), small bowel (35%), and rectum (24%). Significant changes in the
      location of metastatic disease between pre-treatment and the monitoring were
      observed, with the appearance of more extra-abdominal disease. CONCLUSIONS:
      individualization of protocol studies and interpretation of PET, CT and fused
      images were required for evaluation of treatment response to imatinib. Hybrid 18F
      FDG PET/CT provides an accurate determination of the extent of GIST. While the
      most common metastatic site is the liver and peritoneum, in the following cases
      are common extra-abdominal disease.

PMID- 22849498
TI  - Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored
      therapeutic regimen".
AB  - The Montreal Definition and Classification divides Gastroesophageal Reflux
      Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage)
      and extraesophageal syndromes (with acid established association and proposed
      association). In typical GERD symptoms, an 8-week treatment with PPIs is
      satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly
      variable, as they also rely on an appropriate clinical diagnosis of the disease;
      endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety
      (50-70% prevalence) has a different symptomatic response rate, as gastric acid is
      not the sole etiology of symptoms. The possible explanations of treatment failure
      include treatment adherence, PPI metabolism alterations and characteristics, and
      inadequate diagnosis. Refractory symptoms are related to gastric content
      neutralization by the chronic use of PPIs.Extraesophageal manifestations are
      associated with other pathophysiological mechanisms where an autonomic nervous
      system disturbance gives rise to symptoms. In these clinical entities, the
      relationship between symptoms and acid needs to be established in order to
      determine the use of PPIs, or consider other drugs. In other words, so as to
      "custom-tailor the best-fitting therapy" we need to answer the questions for
      whom, for what, how and for how long. Finally, PPI safety and tolerability are
      factors to be considered in elderly patients requiring chronic PPI use, who
      usually have chronic concomitant illnesses.

PMID- 22849499
TI  - Unusual image of lanthanum carbonate in the abdominal radiograph.

PMID- 22849500
TI  - Telangiectasia affected Vater's papilla in Osler Rendu syndrome.

PMID- 22849501
TI  - Gallbladder leiomyoma in absence of immune system disorders: an unusual
      diagnosis.
AB  - Mesenchymal neoplasms of the gallbladder are rare and in particular leiomyomas of
      the gallbladder have been rarely reported, all of them in patients with immune
      system disorders.This is the first report in Spanish of a 23-year-old female
      patient with a gallbladder leiomyoma without associated immunodeficiency. The
      patient lacks a previous history of uterine leiomyoma or any other form of
      neoplasm. She refers several episodes of epygastralgia. A hydatic cyst led to an
      initial diagnosis and the gallbladder was removed by means of simple
      cholecystectomy. The abnormal macroscopic aspect of the sample prompted
      intraoperative biopsy which revealed a benign gallbladder angiomyoma. Subsequent
      immunohistochemical analysis of the resected sample yielded the diagnosis of
      intramural endocavitary leiomyoma negative for EBV and C-kit / CD-117. The
      patient has good general condition and remains asymptomatic 15 months after
      surgery.

PMID- 22849502
TI  - [Information for patients. Pancreatic cancer].

PMID- 22849503
TI  - Megaesophagus and emetic syndrome as first clinical manifestations of
      scleroderma.

PMID- 22849504
TI  - Iliac-appendiceal fistula. An unusual cause of gastrointestinal bleeding.

PMID- 22849505
TI  - Biliary parasite (Ascaris) as a cause of acute pancreatitis. Ultrasound
      diagnosis.

PMID- 22849506
TI  - First severe complication described after Longo hemorrhoidopexy.

PMID- 22849507
TI  - Laparoscopic surgery of an enterovesical fistula of tuberculous origin (terminal
      ileum and sigmoid colon).

PMID- 22849508
TI  - Acute appendicitis by Enterobius vermicularis, an unusual etiology in children.

PMID- 22849510
TI  - Pharmacokinetics and pharmacodynamics of edivoxetine (LY2216684), a
      norepinephrine reuptake inhibitor, in pediatric patients with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Edivoxetine (LY2216684) is a selective and potent norepinephrine
      reuptake inhibitor (NERI). The pharmacokinetics (PK) and pharmacodynamics (PD) of
      edivoxetine were assessed in children and adolescent patients with attention
      deficit/hyperactivity disorder (ADHD) following single and once-daily oral doses
      of edivoxetine. METHODS: During a phase 1 open-label safety, tolerability, and PK
      study, pediatric patients were administered edivoxetine at target doses of 0.05,
      0.1, 0.2 and 0.3 mg/kg, and blood samples were collected to determine plasma
      concentrations of edivoxetine for PK assessments and plasma 3,4
      dihydroxyphenylglycol (DHPG) concentrations for PD assessments. Edivoxetine
      plasma concentrations were measured using liquid chromatography with tandem mass
      spectrometric detection, and DHPG was measured using liquid chromatography with
      electrochemical detection. RESULTS: Edivoxetine PK was comparable between
      children and adolescents. The time to maximum concentration (t(max)) of
      edivoxetine was ~2 hours, which was followed by a mono-exponential decline in
      plasma concentrations with a terminal elimination half-life (t(1/2)) of ~6 hours.
      Dose-dependent increases in area under the edivoxetine plasma concentration
      versus time curve from zero to infinity (AUC(0-infinity)) and maximum plasma
      concentration (C(max)) were observed, and there was no discernable difference in
      the apparent clearance (CL/F) or the apparent volume of distribution at steady
      state (V(ss)/F) across the dose range. In adolescents, edivoxetine caused a
      maximum decrease in plasma DHPG concentrations from baseline of ~28%, most
      notably within 8 hours of edivoxetine administration. CONCLUSION: This initial
      study in pediatric patients with ADHD provides new information on the PK profile
      of edivoxetine, and exposures that decrease plasma DHPG consistent with the
      mechanism of action of a NERI. The PK and PD data inform edivoxetine pharmacology
      and can be used to develop comprehensive population PK and/or PK-PD models to
      guide dosing strategies.

PMID- 22849509
TI  - Can father inclusive practice reduce paternal postnatal anxiety? A repeated
      measures cohort study using the Hospital Anxiety and Depression Scale.
AB  - BACKGROUND: Perinatal research on anxiety and depression has primarily focused on
      mothers. We have limited knowledge of fathers' anxiety during the perinatal
      period yet there is evidence that the parenting capacity of a person can be
      compromised by anxiety and depression. The purpose of this paper is to identify
      the impact of a father inclusive intervention on perinatal anxiety and
      depression. The prime focus of the intervention was to provide education and
      support to fathers of breastfeeding partners with the aim of increasing both
      initiation and duration of breastfeeding. METHODS: A repeated measures cohort
      study was conducted during a RCT that was implemented across eight public
      maternity hospitals in Perth, Western Australia between May 2008 and June 2009. A
      baseline questionnaire which included the Hospital Anxiety and Depression Scale
      (HADS) was administered to all participants on the first night of their hospital
      based antenatal education program and was repeated at six weeks postnatal. SPSS
      version 17 was used for reporting descriptive results. RESULTS: The mean anxiety
      levels at baseline for the fathers in the intervention group (n=289) and control
      group (n=244) were 4.58 and 4.22 respectively. At 6 weeks postnatal (only matched
      pairs), intervention and control group were 3.93 and 3.79. More intervention
      group fathers self-rated less anxiety compared to the fathers in the control
      group from baseline to post test (p=0.048). Depression scores for intervention
      fathers at baseline (mean=1.09) and at six weeks (mean=1.09) were very similar to
      fathers in the control group at baseline (mean=1.11) and at six weeks (mean=1.07)
      with no significant changes. CONCLUSIONS: Both intervention and control group
      fathers experienced some anxiety prior to the birth of their baby, but this was
      rapidly reduced at six weeks. Paternal anxiety is common to new fathers and
      providing them with information and strategies for problem-solving can increase
      their knowledge and potentially lower the risk of postnatal anxiety. TRIAL
      REGISTRATION: (Australian New Zealand Clinical Trials Registry
      ACTRN12609000667213).

PMID- 22849511
TI  - The safety of switching between therapeutic proteins.
AB  - INTRODUCTION: The approval of several biosimilars in the past years has prompted
      discussion on potential safety risks associated with switching to and from these
      products. It has been suggested that switching may lead to safety concerns.
      However, data is limited on the clinical effects of switching. AREAS COVERED: In
      this review we provide an overview of data related to switching between human
      recombinant growth hormones, erythropoietins and granulocyte colony stimulating
      agents. We reviewed data from clinical trials, pharmacovigilance databases and an
      overview of the literature on the frequency of switching between these products.
      The review covers both switching between innovator products within the same
      product class and switching to and from biosimilars. EXPERT OPINION: Data on the
      frequency of switching in clinical practice is scarce, but it seems most frequent
      for erythropoietins. We have found no evidence from clinical trial data or post
      marketing surveillance data that switching to and from different
      biopharmaceuticals leads to safety concerns.

PMID- 22849513
TI  - A tandem segmental duplication (TSD) in green revolution gene Rht-D1b region
      underlies plant height variation.
AB  - * Rht-D1c (Rht10) carried by Chinese wheat (Triticum aestivum) line Aibian 1 is
      an allele at the Rht-D1 locus. Among the Rht-1 alleles, little is known about Rht
      D1c although it determines an extreme dwarf phenotype in wheat. * Here, we cloned
      and functionally characterized Rht-D1c using a combination of Southern blotting,
      target region sequencing, gene expression analysis and transgenic experiments. *
      We found that the Rht-D1c allele was generated through a tandem segmental
      duplication (TSD) of a > 1 Mb region, resulting in two copies of the Rht-D1b. Two
      copies of Rht-D1b in the TSD were three-fold more effective in reducing plant
      height than a single copy, and transformation with a segment containing the
      tandemly duplicated copy of Rht-D1b resulted in the same level of reduction of
      plant height as the original copy in Aibian 1. * Our results suggest that changes
      in gene copy number are one of the important sources of genetic diversity and
      some of these changes could be directly associated with important traits in
      crops.

PMID- 22849515
TI  - Discovery and validation of gene classifiers for endocrine-disrupting chemicals
      in zebrafish (danio rerio).
AB  - BACKGROUND: Development and application of transcriptomics-based gene classifiers
      for ecotoxicological applications lag far behind those of biomedical sciences.
      Many such classifiers discovered thus far lack vigorous statistical and
      experimental validations. A combination of genetic algorithm/support vector
      machines and genetic algorithm/K nearest neighbors was used in this study to
      search for classifiers of endocrine-disrupting chemicals (EDCs) in zebrafish.
      Searches were conducted on both tissue-specific and tissue-combined datasets,
      either across the entire transcriptome or within individual transcription factor
      (TF) networks previously linked to EDC effects. Candidate classifiers were
      evaluated by gene set enrichment analysis (GSEA) on both the original training
      data and a dedicated validation dataset. RESULTS: Multi-tissue dataset yielded no
      classifiers. Among the 19 chemical-tissue conditions evaluated, the transcriptome
      wide searches yielded classifiers for six of them, each having approximately 20
      to 30 gene features unique to a condition. Searches within individual TF networks
      produced classifiers for 15 chemical-tissue conditions, each containing 100 or
      fewer top-ranked gene features pooled from those of multiple TF networks and also
      unique to each condition. For the training dataset, 10 out of 11 classifiers
      successfully identified the gene expression profiles (GEPs) of their targeted
      chemical-tissue conditions by GSEA. For the validation dataset, classifiers for
      prochloraz-ovary and flutamide-ovary also correctly identified the GEPs of
      corresponding conditions while no classifier could predict the GEP from
      prochloraz-brain. CONCLUSIONS: The discrepancies in the performance of these
      classifiers were attributed in part to varying data complexity among the
      conditions, as measured to some degree by Fisher's discriminant ratio statistic.
      This variation in data complexity could likely be compensated by adjusting sample
      size for individual chemical-tissue conditions, thus suggesting a need for a
      preliminary survey of transcriptomic responses before launching a full scale
      classifier discovery effort. Classifier discovery based on individual TF networks
      could yield more mechanistically-oriented biomarkers. GSEA proved to be a
      flexible and effective tool for application of gene classifiers but a similar and
      more refined algorithm, connectivity mapping, should also be explored. The
      distribution characteristics of classifiers across tissues, chemicals, and TF
      networks suggested a differential biological impact among the EDCs on zebrafish
      transcriptome involving some basic cellular functions.

PMID- 22849512
TI  - Are neighbourhood social capital and availability of sports facilities related to
      sports participation among Dutch adolescents?
AB  - BACKGROUND: The aim of this study is to explore whether availability of sports
      facilities, parks, and neighbourhood social capital (NSC) and their interaction
      are associated with leisure time sports participation among Dutch adolescents.
      METHODS: Cross-sectional analyses were conducted on complete data from the last
      wave of the YouRAction evaluation trial. Adolescents (n = 852) completed a
      questionnaire asking for sports participation, perceived NSC and demographics.
      Ecometric methods were used to aggregate perceived NSC to zip code level.
      Availability of sports facilities and parks was assessed by means of geographic
      information systems within the zip-code area and within a 1600 meter buffer.
      Multilevel logistic regression analyses, with neighborhood and individual as
      levels, were conducted to examine associations between physical and social
      environmental factors and leisure time sports participation. Simple slopes
      analysis was conducted to decompose interaction effects. RESULTS: NSC was
      significantly associated with sports participation (OR: 3.51 (95%CI: 1.18;10.41))
      after adjustment for potential confounders. Availability of sports facilities and
      availability of parks were not associated with sports participation. A
      significant interaction between NSC and density of parks within the neighbourhood
      area (OR: 1.22 (90%CI: 1.01;1.34)) was found. Decomposition of the interaction
      term showed that adolescents were most likely to engage in leisure time sports
      when both availability of parks and NSC were highest. CONCLUSIONS: The results of
      this study indicate that leisure time sports participation is associated with
      levels of NSC, but not with availability of parks or sports facilities. In
      addition, NSC and availability of parks in the zip code area interacted in such a
      way that leisure time sports participation is most likely among adolescents
      living in zip code areas with higher levels of NSC, and higher availability of
      parks. Hence, availability of parks appears only to be important for leisure time
      sports participation when NSC is high.

PMID- 22849516
TI  - Combinational therapies for HIV: a focus on EVG/COBI/FTC/TDF.
AB  - INTRODUCTION: The co-formulation of
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
      (EVG/COBI/FTC/TDF) is a new, investigational, once-daily (q.d.) drug, currently
      undergoing Phase II and III clinical trials. Next to the nucleotide/nucleoside
      reverse transcriptase inhibitors FTC and TDF, it contains EVG, the second member
      of the HIV-1 integrase strand transfer inhibitor class, together with its
      pharmacokinetic booster COBI. AREAS COVERED: In this article, the authors review
      EVG/COBI/FTC/TDF, in addition to discussing the single-tablet regimens (STRs)
      containing EFV/FTC/TDF or RPV/FTC/TDF, and the investigational combination pill
      containing dolutegravir, lamivudine and abacavir (DTG/3TC/ABC, 572-Trii pill). A
      Medline review was conducted of Phase II and III trials, as well as a review of
      abstracts from major HIV and infectious disease conferences from 2010 to 2012,
      involving EVG/COBI/FTC/TDF. EXPERT OPINION: Next to the combination of
      EFV/FTC/TDF or RPV/FTC/TDF, the co-formulation of EVG/COBI/FTC/TDF offers a new,
      q.d., single-tablet alternative in treatment-naive HIV patients. EVG/COBI/FTC/TDF
      combines a high efficacy with a good tolerability profile. The effect on the
      renal function and virologic failure with the development of resistance to two or
      more compounds present in EVG/COBI/FTC/TDF, requires further monitoring. STRs
      certainly bring the standard for HIV treatment and drug development to a higher
      level.

PMID- 22849517
TI  - An engineered ClyA nanopore detects folded target proteins by selective external
      association and pore entry.
AB  - Nanopores have been used in label-free single-molecule studies, including
      investigations of chemical reactions, nucleic acid analysis, and applications in
      sensing. Biological nanopores generally perform better than artificial nanopores
      as sensors, but they have disadvantages including a fixed diameter. Here we
      introduce a biological nanopore ClyA that is wide enough to sample and
      distinguish large analyte proteins, which enter the pore lumen. Remarkably, human
      and bovine thrombins, despite 86% sequence identity, elicit characteristic ionic
      current blockades, which at -50 mV differ in their main current levels by 26 +/-
      1 pA. The use of DNA aptamers or hirudin as ligands further distinguished the
      protein analytes. Finally, we constructed ClyA nanopores decorated with
      covalently attached aptamers. These nanopores selectively captured and
      internalized cognate protein analytes but excluded noncognate analytes, in a
      process that resembles transport by nuclear pores.

PMID- 22849518
TI  - Usefulness of antibody index assessment in cerebrospinal fluid from patients
      negative for total-IgG oligoclonal bands.
AB  - BACKGROUND: Testing for cerebrospinal fluid (CSF)-restricted oligoclonal bands
      (OCB) by isoelectric focusing is used to detect intrathecally produced total IgG.
      By contrast, antibody indices (AI) are assessed to test for intrathecally
      produced antigen-specific IgG. A number of previous cases reports have suggested
      that AI testing might be more sensitive than OCB testing in detecting intrathecal
      IgG synthesis. FINDINGS: Here we report on 21 patients with positive AI for
      either herpes simplex virus, varicella zoster virus, cytomegalovirus, measles
      virus, rubella virus, or Borrelia burgdorferi in the absence of total-IgG OCB
      and, accordingly, in the presence of a normal total-IgG CSF/serum ratio.
      CONCLUSION: Our findings indicate that AI testing should not generally be omitted
      in OCB-negative patients and provide a rationale for systematic and prospective
      studies on the comparative sensitivity and specificity of AI and total-IgG OCB
      testing in infectious and other diseases of the CNS.

PMID- 22849519
TI  - Anticancer activities of the extract from Longkong (Lansium domesticum) young
      fruits.
AB  - "Longkong"(Lansium domesticum Corr., Family: Meliaceae) is a fruit found in the
      south of Thailand. This plant has been used in traditional medicines. OBJECTIVES:
      To investigate the antiproliferative activities and the phytoconstituents of
      Longkong extracts. MATERIALS AND METHODS: Cytotoxicity and apoptotic activity of
      48 extracts were tested using the SRB assay and acridine orange (AO)/ethidium
      bromide (EB) staining, respectively. The extracts which gave the highest
      anticancer activity were selected to prepare the semipurified extracts and
      analysis for the constituents by gas chromatography-mass spectrometry (GC/MS).
      RESULTS: The highest percentage yield (59.38%) was from the cold water extract of
      Longkong ripe fruits (RFWC). The highest total phenolic and flavonoid contents
      were observed in cold and hot methanol extract of Longkong stalks (STMC and
      STMH). The hot and cold chloroform young Longkong fruit extracts (YFCH and YFCC)
      exhibited a cytotoxic effect (IC(50) < 1 mg/mL) against cancer cells. For
      apoptotic induction, YFCH demonstrated the highest activity against KB of 13.84
      +/- 4.21% at 0.5 mg/mL which was 0.88 and 1.35 times of cisplatin and 5-FU,
      respectively, while apoptotic cells in HT-29 were 8.68 +/- 1.85% at 5 mg/mL,
      which was 0.61 and 1.43 times of cisplatin and 5-FU, respectively. YFCC showed
      the highest apoptotic effect against KB cells at 10.70 +/- 2.15% at 0.5 mg/mL,
      which was 0.68 and 1.07 times of cisplatin and 5-FU, respectively. The major
      phytoconstituents in YFCH were hexadecanoic acid (11.53%) and ethyl oleate
      (10.58%). DISCUSSION AND CONCLUSION: The crude extracts of Longkong showed
      anticancer activities and may provide new lead compounds for the development of
      anticancer products.

PMID- 22849520
TI  - Improved annotation of a plant pathogen genome Xanthomonas oryzae pv. oryzae
      PXO99A.
AB  - Many bacterial genomes have been sequenced and stored in public databases now, of
      which Reference Sequence (RefSeq) is the most widely used one. However, the
      annotation in RefSeq is still unsatisfactory. The present analysis is focused on
      the re-annotation of an important plant pathogen genome Xanthomonas oryzae pv.
      oryzae PXO99A (Xoo PXO99A), which is the causal agent of bacterial blight on
      rice. Based on the parameters of 28 nucleotide frequencies and support vector
      machine algorithm, 41 originally annotated hypothetical genes were recognized as
      noncoding sequences, which were further supported by principal component analysis
      and other evidence. Ten of them were tested with reverse transcription-polymerase
      chain reaction experiments (RT-PCR), and all of them were confirmed to be
      noncoding sequences. Furthermore, 197 potential new genes not annotated in RefSeq
      were both recognized by two ab initio gene finding programs. Most of them only
      have sequence similarities with part of the known genes in other species, so they
      are unlikely to be protein-coding genes. Twelve potential new genes have high
      full-length sequence similarities with function-known genes, which are very
      likely to be true protein-coding genes. All the 12 potential genes were tested
      with RT-PCR, and 11 of them (92%) were successfully amplified in cDNA template.
      The RT-PCR experiments confirm that our theoretical prediction has high accuracy.
      The improvement of Xoo PXO99A annotation is helpful for the research of
      lifestyle, metabolism, and pathogenicity of this important plant pathogen. The
      improved annotation can be obtained from  http://211.69.128.148/Xoo .

PMID- 22849521
TI  - Ultrastructural changes of smooth muscles in varicocele veins.
AB  - BACKGROUND: Varicocele is a dilatation of the pampiniform venous plexus and
      internal spermatic veins. It affects about 15-20% of male population and can
      cause infertility. OBJECTIVE: To describe the most significant ultrastructural
      changes of the smooth muscle cells in grade 3 varicocele veins. METHODS: The
      authors analyzed 2- to 3-cm tracts of pampiniform venous plexus from 20 patients
      who underwent varicocelectomy for left varicocele. Light microscopic examination
      was performed with Van Gieson's stain. Ultrastructural examination was done using
      scanning and transmission electron microscopy. RESULTS: Light microscopic
      examination revealed irregularity and separation of medial smooth muscle cells by
      abundant collagen fibers in varicocele veins. On scanning electron microscopy,
      the medial layer of varicocele veins showed hypertrophy, irregularity, and
      separation of the outer longitudinal smooth muscle cells and deposition of
      numerous fatty globules in between muscle fibers. Transmission electron
      microscopy showed marked indentation and chromatin condensation of the nucleus,
      presence of clear vacuoles and myelin figures in the cytoplasm and plasmalemmal
      projections and formation of ghost bodies. Furthermore, smooth muscle cells were
      found to have pseudopodia-like projections around adjacent elastic and collagen
      fibers. CONCLUSIONS: The degenerative changes observed in smooth muscle cells and
      presence of abundant collagen fibers in the medial layer may contribute to the
      development of the varicocele of pampiniform venous plexus. Further molecular
      studies are required to shed more light for the underlying mechanism.

PMID- 22849522
TI  - Light and electron microscopic features of synovium in patients with psoriatic
      arthritis.
AB  - INTRODUCTION: Few ultrastructural studies have been reported in psoriatic
      arthritis (PsA). The authors report a series of synovial biopsies with emphasis
      on patients with early disease to look for distinctive light (LM) and electron
      microscopic (EM) features of possible importance. METHODS: The authors examined
      synovial biopsies obtained primarily by needle biopsy from 13 PsA patients using
      LM and/or EM. Sections from 12 patients were evaluated by LM for vascularity,
      synovial lining thickness, fibrin deposition, and inflammation via a semi
      quantitative scale. Nine EM specimens were descriptively analyzed. Clinical,
      synovial fluid (SF), and radiographic characteristics were recorded. RESULTS:
      Patients were mostly male, with mean disease duration before biopsy of 2.19 +/-
      2.60 years; 7 patients had arthritis for less than 1 year. All patients had
      peripheral arthritis, 2 had axial involvement. SFs disclosed predominance of
      polymorphonuclear leukocytes. LM demonstrated proliferation of synovial lining
      cells, lymphocyte and plasma cell infiltration, as well as dramatic clusters of
      small vessels in the superficial synovium. EMs showed more detailed vascular
      changes, including small, subendothelial, electron-dense deposits and scattered
      microparticles in vessel lumens and walls. CONCLUSIONS: Prominent vascularity is
      confirmed as an important feature of some PsA. Vascular changes and other
      features, including the first EM demonstration of microparticles in PsA
      (identified as potent factors in other inflammatory joint diseases), are
      potential targets for therapy.

PMID- 22849523
TI  - Alpers syndrome: an unusual etiology of failure to thrive.

PMID- 22849524
TI  - Injury of peripheral muscles in smokers with chronic obstructive pulmonary
      disease.
AB  - Muscle injury has clinical relevance in diseased individuals because it is
      associated with muscle dysfunction in terms of decreased strength and/or
      endurance. This study was aimed at answering three questions: whether the
      presence of chronic obstructive pulmonary disease (COPD) is associated with
      peripheral muscle injury; whether muscle injury is associated with some of the
      relevant functional impairment in the muscles; and whether muscle injury can be
      solely justified by deconditioning. Twenty-one male COPD patients were eligible
      for the study. Seven healthy volunteers recruited from the general population
      were included as controls. Function of the quadriceps muscle was assessed through
      specific single-leg exercise (strength and endurance). Cellular (light
      microscopy) and subcellular (electron microscopy) techniques were used to
      evaluate muscle injury on biopsies from the vastus lateralis muscle. Signs of
      injury were found in muscles from both control and COPD patients, not only in
      cases showing severe airflow obstruction but also in the mild or moderate stages
      of the disease. Current smoking and presence of COPD were significantly
      associated with increased injury of the muscle as assessed by light and electron
      microscopy techniques. The authors conclude that peripheral muscle injury is
      evident in mild, moderate, and severe stages of COPD even in the absence of
      respiratory failure, hypercapnia, chronic steroid treatment, low body weight, or
      some coexisting disease. These findings support the theory that systemic factors
      with deleterious effect are acting on peripheral muscles of smokers with COPD,
      increasing the susceptibility of the muscle fibers to membrane and sarcomere
      injury.

PMID- 22849525
TI  - Ultrastructural changes in platelet membranes due to cigarette smoking.
AB  - It is estimated that 1.3 billion people currently smoke cigarettes or other
      tobacco products. Smoking is becoming an epidemic worldwide and is a major risk
      factor for atherosclerosis and heart disease. Research has shown that smoking
      causes changes in platelet membrane fluidity and Na(+)/K(+)ATPase activity. The
      aim of the current research is to determine if these changes in membrane fluidity
      are ultrastructurally visible. Thirty-five experimental and control subjects were
      selected for the study. Smokers had smoked on average 2 cigarettes per day for 5
      10 years. Smears of platelet-rich plasma were prepared for scanning electron
      microscopy and viewed with a Zeiss ULTRA plus FEG-SEM with InLens capabilities.
      Platelet surface morphology was viewed at 1 kV and micrographs were taken at
      80,000-200,000* machine magnification. A difference in the globular nature of the
      platelet membrane of smokers was visible; additionally, it seemed as if surface
      pseudopodia were more pronounced than in healthy individuals. No apoptotic or
      necrotic platelet morphology was noted. Research has noted changed membrane
      fluidity and the study concludes by suggesting that this is visible
      ultrastructurally. Therefore, changes in membrane fluidity are structurally
      visible and translate into a more globular and bulbous appearance of the membrane
      surface.

PMID- 22849526
TI  - Not only melatonin but also caffeic acid phenethyl ester protects kidneys against
      aging-related oxidative damage in Sprague Dawley rats.
AB  - Microscopic features and antioxidant status of kidneys of young, old, and caffeic
      acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats
      were evaluated. Aging-related tubular and glomerular changes were evident. The
      most prominent tubular alterations were massive vacuole formation, mitochondrial
      degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level
      was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001),
      and glutathione peroxidase (GPx) activities (p < .05), and total glutathione
      (GSH) level were decreased in old animals. Melatonin significantly reduced tissue
      MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx
      activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also
      significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p <
      .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean
      tissue MDA levels of melatonin and CAPE-administered rats were even lower than
      those of young rats (p < .05). In conclusion, tubular and glomerular structures
      and tissue antioxidant enzyme activities were very well preserved in CAPE and
      melatonin-administered rats.

PMID- 22849527
TI  - From pluripotent stem cells to multifunctional cordocytic phenotypes in the human
      brain: an ultrastructural study.
AB  - Light microscopy and transmission electron microscopy were used to investigate
      surgical cases in a variety of pathological conditions (thromboses, tumors,
      cerebrovascular malformations, Moyamoya disease) to identify and characterize
      different phenotypes belonging to a new interstitial cell recently described
      ultrastructurally in the brain and here named "cordocyte." Also, this work is an
      attempt to identify and characterize precursor/stem cells for cordocytic lineage
      in the perivascular areas, within perivascular nerves and pia mater (now
      considered a cordocytic-vascular tissue). Unexpected relationships and functions
      emerge from observations concerning these phenotypes, almost ubiquitous, but not
      yet fully studied in the brain.

PMID- 22849528
TI  - A quantitative ultrastructural study of circulating (monocytic) cells interacting
      with endothelial cells in high oxygen-injured and spontaneously re-forming (FVB)
      mouse lung capillaries.
AB  - The present study demonstrates the fine structure of blood-borne (monocytic)
      circulating cells (CCs), and their interaction with endothelial cells, in a mouse
      model of lung capillary injury and repair. Quantitative analysis highlights the
      diversity of CC profiles entering the lung, where they form contact and
      adhesion/fusion sites to endothelial plasmalemmal membranes, and to complexes of
      endothelial/basement membrane remnants, as capillary networks reorganize over
      time. Temporal patterns of CC influx and efflux in the lung, changing CC
      phenotypes, and the range of CC interactions with endothelium, underscore the
      potential for a complex angiogenic/immunogenic response, as capillary networks
      stabilize and undergo expansion and growth.

PMID- 22849529
TI  - Ultrastructural features of NUT midline carcinoma.
AB  - Midline carcinomas associated with the nuclear protein in testis (NUT) gene
      rearrangement are rare, aggressive tumors that have been diagnosed most commonly
      in the head, neck, mediastinum, and upper aerodigestive tract. The
      ultrastructural features associated with this tumor have thus far received only
      brief comment and have never been illustrated. The authors provide a more
      extensive description and illustrate the electron microscopic findings in a
      typical case of NUT midline carcinoma, confirmed by cytogenetic and fluorescence
      in situ hybridization studies. This tumor was composed of cells displaying large,
      irregularly shaped nuclei with prominent compact nucleoli and abundant cytoplasm
      containing prominent bundles of tonofilaments, occasional clusters of pleomorphic
      granules, small numbers of lipid inclusions, and rare glycogen deposits. The
      cells exhibited stubby microvillous projections, were intermittently enveloped by
      basal lamina, and were interjoined by numerous well-formed desmosomal-type
      junctions and occasional junctional complexes. The authors propose that this
      constellation of ultrastructural features can prove helpful in discriminating NUT
      midline carcinoma from similar appearing entities.

PMID- 22849530
TI  - Emerging role of IEX-1 in tumor pathogenesis and prognosis.

PMID- 22849534
TI  - Photogeneration of benzhydryl cations by near-UV laser flash photolysis of
      pyridinium salts.
AB  - Laser flash irradiation of substituted N-benzhydryl pyridinium salts yields
      benzhydryl cations (diarylcarbenium ions) and/or benzhydryl radicals
      (diarylmethyl radicals). The use of 3,4,5-triamino-substituted pyridines as
      photoleaving groups allowed us to employ the third harmonic of a Nd/YAG laser
      (355 nm) for the photogeneration of benzhydryl cations. In this way, benzhydryl
      cations can also be photogenerated in the presence of aromatic compounds and in
      solvents which are opaque at the wavelength of the quadrupled Nd/YAG laser (266
      nm). To demonstrate the scope and limitations of this method, the rate constants
      for the bimolecular reactions of benzhydryl cations with several substituted
      pyridines were determined in acetonitrile and with water in acetone. The obtained
      data agree with results obtained by stopped-flow UV-vis spectroscopic
      measurements. The rate constants for the reaction of the 4,4'-bis[methyl(2,2,2
      trifluoroethyl)amino]benzhydrylium ion with 4-(dimethylamino)pyridine were also
      determined in dimethyl sulfoxide, N,N-dimethylformamide, and acetone. From the
      second-order rate constants, we derived the nucleophilicity parameters N and s(N)
      for the substituted pyridines, as defined by the linear free energy relationship,
      log k(2) = s(N)(N + E).

PMID- 22849533
TI  - The effects of aripiprazole on electrocardiography in children with pervasive
      developmental disorders.
AB  - OBJECTIVES: Psychotropic medications, including the atypical antipsychotics, have
      historically been scrutinized for cardiac effects and risk of sudden death.
      Aripiprazole is an atypical antipsychotic approved for pediatric use in
      schizophrenia, bipolar I disorder, and autistic disorder. Adult studies have
      evaluated aripiprazole's effects on electrocardiograms, but no pediatric studies
      have been published to date. METHODS: Electrocardiographic data were collected
      from children and adolescents participating in a 14-week, prospective, open-label
      study (n=25) of aripiprazole for irritability in pervasive developmental disorder
      not otherwise specified and Asperger's disorder. A 12-lead electrocardiogram was
      obtained at the baseline and end point visits. The electrocardiograms were
      evaluated for abnormal findings, and the PR, QRS, QT(c), and RR intervals were
      recorded. The QT interval was corrected using Bazett's, United States Food and
      Drug Administration (FDA) Pharmacology Division, and Fridericia's formulas.
      RESULTS: Twenty-four subjects received both baseline and posttreatment
      electrocardiograms. The mean age was 8.6 years (range 5-17 years). The average
      final aripiprazole dose was 7.8 mg/day (range 2.5-15 mg/day). There were no
      significant differences noted with the PR, QRS, RR, and QT(c) intervals after
      aripiprazole therapy. Also, there was no significant correlation between the dose
      given and the percent change in the QT(c). No post-treatment QT(c) exceeded 440
      ms. CONCLUSIONS: To our knowledge, this is the first systematic evaluation of the
      cardiac effects of aripiprazole in children and adolescents. The results are
      consistent with previously published literature in adults that aripiprazole has
      no significant cardiac effects and can be deemed a low risk for causing sudden
      death. It will be important to confirm these findings in a randomized controlled
      trial.

PMID- 22849532
TI  - A parapatric propensity for breeding precludes the completion of speciation in
      common teal (Anas crecca, sensu lato).
AB  - Speciation is a process in which genetic drift and selection cause divergence
      over time. However, there is no rule dictating the time required for speciation,
      and even low levels of gene flow hinder divergence, so that taxa may be poised at
      the threshold of speciation for long periods of evolutionary time. We sequenced
      mitochondrial DNA (mtDNA) and eight nuclear introns (nuDNA) to estimate genomic
      levels of differentiation and gene flow between the Eurasian common teal (Anas
      crecca crecca) and the North American green-winged teal (Anas crecca
      carolinensis). These ducks come into contact in Beringia (north-eastern Asia and
      north-western North America) and have probably done so, perhaps cyclically, since
      the Pliocene-Pleistocene transition, ~2.6 Ma, when they apparently began
      diverging. They have diagnosable differences in male plumage and are 6.9%
      divergent in the mtDNA control region, with only 1 of 58 crecca and 2 of 86
      carolinensis having haplotypes grouping with the other. Two nuclear loci were
      likewise strongly structured between these teal (Phi(st) >= 0.35), but six loci
      were undifferentiated or only weakly structured (Phi(st) = 0.0-0.06). Gene flow
      between crecca and carolinensis was ~1 individual per generation in both
      directions in mtDNA, but was asymmetrical in nuDNA, with ~1 and ~20 individuals
      per generation immigrating into crecca and carolinensis, respectively. This study
      illustrates that species delimitation using a single marker oversimplifies the
      complexity of the speciation process, and it suggests that even with divergent
      selection, moderate levels of gene flow may stall the speciation process short of
      completion.

PMID- 22849535
TI  - Peripancreatic vascular involvements of autoimmune pancreatitis.
AB  - BACKGROUND AND AIM: Although peripancreatic vascular lesions are occasionally
      encountered in autoimmune pancreatitis (AIP), there are few reports focusing on
      these involvements. We aimed to investigate the peripancreatic vascular
      involvements associated with AIP. METHODS: We retrospectively analyzed 54 AIP
      patients who met the International Consensus Diagnostic Criteria for AIP between
      July 2003 and October 2010. All of the 54 patients were subjected to multiphasic
      multidetector computed tomography, and the prevalence, location and prognosis of
      peripancreatic vascular involvements were investigated. RESULTS: Of the 54 AIP
      patients, 24 (44.4%) exhibited involvements in the form of peripancreatic
      vascular lesions (stenoses of the splenic vein in 22 and of the superior
      mesenteric-portal vein in 13, development of perigastric collateral circulation
      in 18, gastric varices with a red color sign in one and thrombosis inside the
      portal vein in one). Diffuse-type AIP was associated with a significantly higher
      prevalence of vascular involvements compared with focal-type AIP (P = 0.033). A
      total of 14 out of 16 patients who underwent corticosteroid treatment showed
      improvement in vascular lesions. One case followed up without corticosteroid
      treatment and presenting an obstruction of the splenic vein exhibited
      involvements in the form of an infarction and hemorrhagic cysts of the spleen and
      ultimately underwent distal pancreatectomy and splenectomy. CONCLUSIONS:
      Autoimmune pancreatitis patients show a high prevalence of peripancreatic
      vascular involvements. Thus, patients with vascular involvements are suitable
      candidates for steroid therapy with evaluation of its potential merits and
      demerits, even if they are asymptomatic.

PMID- 22849536
TI  - Effect of sweet orange aroma on experimental anxiety in humans.
AB  - OBJECTIVES: The objective of this study was to evaluate the potential anxiolytic
      effect of sweet orange (Citrus sinensis) aroma in healthy volunteers submitted to
      an anxiogenic situation. DESIGN: Forty (40) male volunteers were allocated to
      five different groups for the inhalation of sweet orange essential oil (test
      aroma: 2.5, 5, or 10 drops), tea tree essential oil (control aroma: 2.5 drops),
      or water (nonaromatic control: 2.5 drops). Immediately after inhalation, each
      volunteer was submitted to a model of anxiety, the video-monitored version of the
      Stroop Color-Word Test (SCWT). OUTCOME MEASURES: Psychologic parameters (state
      anxiety, subjective tension, tranquilization, and sedation) and physiologic
      parameters (heart rate and gastrocnemius electromyogram) were evaluated before
      the inhalation period and before, during, and after the SCWT. RESULTS: Unlike the
      control groups, the individuals exposed to the test aroma (2.5 and 10 drops)
      presented a lack of significant alterations (p>0.05) in state-anxiety, subjective
      tension and tranquillity levels throughout the anxiogenic situation, revealing an
      anxiolytic activity of sweet orange essential oil. Physiologic alterations along
      the test were not prevented in any treatment group, as has previously been
      observed for diazepam. CONCLUSIONS: Although more studies are needed to find out
      the clinical relevance of aromatherapy for anxiety disorders, the present results
      indicate an acute anxiolytic activity of sweet orange aroma, giving some
      scientific support to its use as a tranquilizer by aromatherapists.

PMID- 22849537
TI  - The severity of dental caries in adults aged 35 to 44 years residing in the
      metropolitan area of a large city in Brazil: a cross-sectional study.
AB  - BACKGROUND: In recent decades, studies in the field of public health have
      increasingly focused on social determinants that affect the health-illness
      process. The epidemiological perspective considers oral health to be a reflection
      of socioeconomic and environmental aspects, and it is particularly influenced by
      the social context. The aim of the present study was to assess the association
      between the severity of dental caries among adults aged 35 to 44 years and
      characteristics on the different levels at which the determinants of caries
      operate (individual, social structure and social context). METHODS: A home-based,
      cross-sectional field study was carried out involving a sample of 1,150 adults
      (35 to 44 years of age) residing in metropolitan Belo Horizonte, Brazil. The DMFT
      (decayed, missing, filled tooth) index (>=14) was used to determine the severity
      of dental caries. Bivariate and multivariate analyses were carried out using the
      Poisson regression model with the level of significance set at 5% (p < 0.05) and
      95% confidence intervals. RESULTS: The majority of the participants (68.5%) had
      high caries severity. The rate of high-severity caries in the group between 40
      and 44 years of age was 1.15-fold (CI: 1.04-1.26) greater than that among those
      aged 35 to 39 years. A greater prevalence of high caries severity was found among
      those who frequently visited the dentist (PR = 1.18; CI: 1.07-1.30), those with a
      lower income (PR = 1.11; CI: 1.01-1.23), those who reported that their
      neighborhood did not come together in the previous year to petition political
      leaders for benefits (PR = 1.16; CI: 1.05-1.28) and those who are unable to make
      decisions (without empowerment) (PR = 1.12; CI: 1.01-1.24). CONCLUSIONS: The
      present study revealed high dental caries severity in adults, which was
      associated with individual characteristics, health-related behavior and social
      structure and contextual variables. These findings underscore the importance of
      considering social determinants involved in the health-illness process when
      carrying out epidemiological studies on dental caries.

PMID- 22849538
TI  - Short-term N2 fixation kinetics in a moss-associated cyanobacteria.
AB  - N(2) fixation by moss-associated cyanobacteria plays an important role in the
      nitrogen cycling of terrestrial ecosystems. Recent studies have mainly focused on
      boreal ecosystems; little is known about such association in other ecosystems.
      Moss-associated cyanobacteria are subject to rapid changes (hourly or less) in
      environmental conditions that may affect N(2) fixation kinetics. Using a recently
      developed method (Acetylene Reduction Assays by Cavity ring-down laser Absorption
      Spectroscopy, ARACAS) with higher sensitivity and sampling frequency than the
      conventional method, we characterize short-term kinetics of N(2) fixation by
      cyanobacteria on moss carpets from warm and cold temperate forests. We report the
      identification of a heretofore unknown multispecies true-moss-cyanobacteria
      diazotrophic association. We demonstrate that short-term change in abiotic
      variables greatly influences N(2) fixation. We also show that difference in
      relative proportion of two epiphytic diazotrophs is consistent with divergent
      influences of temperature on their N(2) fixation kinetics. Further research is
      needed to determine whether this difference is consistent with a latitudinal
      trend.

PMID- 22849539
TI  - Light on the structural communication in Ras GTPases.
AB  - The graph theory was combined with fluctuation dynamics to investigate the
      structural communication in four small G proteins, Arf1, H-Ras, RhoA, and Sec4.
      The topology of small GTPases is such that it requires the presence of the
      nucleotide to acquire a persistent structural network. The majority of
      communication paths involves the nucleotide and does not exist in the unbound
      forms. The latter are almost devoid of high-frequency paths. Thus, small Ras
      GTPases acquire the ability to transfer signals in the presence of nucleotide,
      suggesting that it modifies the intrinsic dynamics of the protein through the
      establishment of regions of hyperlinked nodes with high occurrence of correlated
      motions. The analysis of communication paths in the inactive (S(GDP)) and active
      (S(GTP)) states of the four G proteins strengthened the separation of the Ras
      like domain into two dynamically distinct lobes, i.e. lobes 1 and 2,
      representing, respectively, the N-terminal and C-terminal halves of the domain.
      In the framework of this separation, interfunctional states and interfamily
      differences could be inferred. The structure network undergoes a reshaping
      depending on the bound nucleotide. Nucleotide-dependent divergences in structural
      communication reach the maximum in Arf1 and the minimum in RhoA. In Arf1, the
      nucleotide-dependent paths essentially express a communication between the G box
      4 (G4) and distal portions of lobe 1. In the S(GDP) state, the G4 communicates
      with the N-term, while, in the S(GTP) state, the G4 communicates with the switch
      II. Clear differences could be also found between Arf1 and the other three G
      proteins. In Arf1, the nucleotide tends to communicate with distal portions of
      lobe 1, whereas in H-Ras, RhoA, and Sec4 it tends to communicate with a cluster
      of aromatic/hydrophobic amino acids in lobe 2. These differences may be linked,
      at least in part, to the divergent membrane anchoring modes that would involve
      the N-term for the Arf family and the C-term for the Rab/Ras/Rho families.

PMID- 22849540
TI  - A glutathione-based system for defense against carbonyl stress in Haemophilus
      influenzae.
AB  - BACKGROUND: adhC from Haemophilus influenzae encodes a glutathione-dependent
      alcohol dehydrogenase that has previously been shown to be required for
      protection against killing by S-nitrosoglutathione (GSNO). This group of enzymes
      is known in other systems to be able to utilize substrates that form adducts with
      glutathione, such as aldehydes. RESULTS: Here, we show that expression of adhC is
      maximally induced under conditions of high oxygen tension as well as specifically
      with glucose as a carbon source. adhC could also be induced in response to
      formaldehyde but not GSNO. An adhC mutant was more susceptible than wild-type
      Haemophilus influenzae Rd KW20 to killing by various short chain aliphatic
      aldehydes, all of which can be generated endogenously during cell metabolism but
      are also produced by the host as part of the innate immune response. CONCLUSIONS:
      These results indicate that AdhC plays a role in defense against endogenously
      generated reactive carbonyl electrophiles in Haemophilus influenzae and may also
      play a role in defense against the host innate immune system.

PMID- 22849541
TI  - High concordance of parent and teacher attention-deficit/hyperactivity disorder
      ratings in medicated and unmedicated children with autism spectrum disorders.
AB  - OBJECTIVE: Parent and teacher ratings of core attention-deficit/hyperactivity
      disorder (ADHD) symptoms, as well as behavioral and emotional problems commonly
      comorbid with ADHD, were compared in children with autism spectrum disorders
      (ASD). METHOD: Participants were 86 children (66 boys; mean: age=9.3 years,
      intelligence quotient [IQ]=84) who met American Psychiatric Association
      Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria
      for an ASD on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism
      Diagnostic Observation Schedule (ADOS). Parent and teacher behavioral ratings
      were compared on the Conners' Parent and Teacher Rating Scales (CPRS-R; CTRS-R).
      The degree to which age, ASD subtype, severity of autistic symptomatology, and
      medication status mediated this relationship was also examined. RESULTS:
      Significant positive correlations between parent and teacher ratings suggest that
      a child's core ADHD symptoms-as well as closely related externalizing symptoms
      are perceived similarly by parents and teachers. With the exception of
      oppositional behavior, there was no significant effect of age, gender, ASD
      subtype, or autism severity on the relationship between parent and teacher
      ratings. In general, parents rated children as having more severe symptomatology
      than did teachers. Patterns of parent and teacher ratings were highly correlated,
      both for children who were receiving medication, and for children who were not.
      CONCLUSIONS: Parents and teachers perceived core symptoms of ADHD and closely
      related externalizing problems in a similar manner, but there is less agreement
      on ratings of internalizing problems (e.g., anxiety). The clinical implication of
      these findings is that both parents and teachers provide important behavioral
      information about children with ASD. However, when a clinician is unable to
      access teacher ratings (e.g., during school vacations), parent ratings can
      provide a reasonable estimate of the child's functioning in these domains in
      school. As such, parent ratings can be reliably used to make initial diagnostic
      and treatment decisions (e.g., medication treatment) regarding ADHD symptoms in
      children with ASDs.

PMID- 22849542
TI  - RNAi-mediated gene silencing in cancer therapy.
AB  - INTRODUCTION: This review presents the intriguing success of RNA interference
      (RNAi)-mediated gene silencing and its advantages and obstacles in cancer
      therapy. AREAS COVERED: RNAi has implications in metabolic disease, viral
      hepatitis, cardiovascular and cerebrovascular diseases, HIV, neurodegenerative
      disorders and cancer. RNAi can enhance the specificity and efficacy of
      therapeutic intervention for human diseases while at the same time reducing
      toxicity. The existing research related to gene therapy suggests encouraging
      prospects of a new high-efficiency and low-toxicity anti-tumor therapy. Although
      gene therapy is still in the experimental research phase, in the near future,
      this method will become an important means for the treatment of cancer therapies
      and it will be widely used in clinical practice. EXPERT OPINION: RNAi-based drug
      development is still in preclinical trial and several challenges limit the use of
      RNAi in the clinic. It is believed that further investigation of the mechanisms
      of RNAi-based therapies will help overcome these limitations and provide powerful
      weapons in the oncology clinic.

PMID- 22849543
TI  - LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is
      predictive for tumor cell spread and overall survival.
AB  - BACKGROUND: We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581) in
      primary ovarian tumors is predictive for the presence of disseminated tumor cells
      (DTC) in the bone marrow (BM). For therapy-monitoring, it would be highly
      desirable to establish a blood-based biomarker. Therefore, we quantified
      circulating DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery and
      after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal
      loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic
      significance of LOH. METHODS: cirDNA was fractionated into high- and low
      molecular-weight fraction (HMWF, LMWF) for LOH-profiling, utilizing PCR-based
      fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by
      immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. RESULTS: cirDNA
      levels in the HMWF before surgery were predictive for residual tumor load (p =
      0.017). After chemotherapy, we observed a significant decline of cirDNA in the
      LMWF (p = 0.0001) but not in the HMWF. LOH was prevalently detected in the LMWF
      with an overall frequency of 67%, only moderately ablating after chemotherapy
      (45%). Before surgery, LOH in the LMWF at marker D10S1765 and D13S218
      significantly correlated with tumor grading and FIGO stage (p = 0.033, p = 0.004,
      respectively). In both combined fractions, LOH at D6S1581 additionally associated
      with overall survival (OS) (p = 0.030). Moreover, solely LOH at D10S1765 in LMWF
      after therapy correlated with DTC in BM after therapy (p = 0.017). CONCLUSION: We
      demonstrate the applicability and necessity of DNA-fractionation prior to
      analyzing circulating LOH and identify LOH at D10S1765 and D6S1581 as novel blood
      based biomarkers for ovarian cancer, being relevant for therapy-monitoring.

PMID- 22849544
TI  - Amide derivatives of benzene-sulfonanilide, pharmaceutical composition thereof
      and method for cancer treatment using the same (US20120095092).
AB  - A series of sulfonamide derivatives incorporating an aromatic scaffold based on
      1,4-phenylene diamine was prepared by a succession of five reactions. The lead
      molecule of these compounds was nimesulide (4-nitro-2-phenoxymethane
      sulfoanilide), a cyclooxygenase (COX) inhibitor acting on both COX-1 and 2
      isoforms, with some selectivity for COX-2. The new compounds from the patent are
      claimed to act as efficient antitumor agents, against a multitude of tumor types,
      such as leukemia, non-small cell lung cancer, colon cancer, brain cancer,
      melanoma, ovarian cancer, etc., although no COX inhibition data or other
      rationale to explain their biological effects are provided. As these compounds
      incorporate a methanesulfonamide moiety it is not unexpected that they may also
      appreciably inhibit tumor-associated carbonic anhydrases (CAs), such as isoforms
      CA IX and XII.

PMID- 22849545
TI  - Prospective comparison between buffered 1% lidocaine-epinephrine and skin cooling
      in reducing the pain of local anesthetic infiltration.
AB  - BACKGROUND: Pain associated with the infiltration of local anesthesia is
      attributed to the acidity of the solution. Buffering with sodium bicarbonate has
      been used widely to reduce this affect. Growing evidence supports skin cooling
      (cryoanalgesia) as a measure to reduce infiltration pain. OBJECTIVE: To compare
      the effect of 1% lidocaine-epinephrine [1:100,000] buffered with sodium
      bicarbonate with skin cooling for 2 minutes with ice in reducing the pain of
      infiltration of anesthetic solution. METHODS AND MATERIALS: Sixty healthy
      volunteers were recruited for this prospective study. Each subject received an
      intradermal injection of buffered solution in one arm and injection of unbuffered
      solution after ice application in the other arm. Immediately after each
      injection, subjects rated pain of infiltration on a 100-mm visual analog scale.
      Pain scores were compared using the paired t-test. RESULTS: Sixty percent of
      subjects reported that pain of infiltration was greater after skin cooling than
      with buffered solution. Mean +/- standard deviation pain scores were 24.8 +/-
      21.7 for skin cooling and 21.1 +/- 20.8 for buffered solution; this difference
      was not statistically significant. CONCLUSION: There is no significant difference
      between buffered anesthetic solution (buffering) and skin cooling in reducing the
      pain of infiltration of 1% lidocaine - epinephrine.

PMID- 22849546
TI  - Ten-day sequential versus triple therapy for Helicobacter pylori eradication: a
      prospective, open-label, randomized trial.
AB  - BACKGROUND AND AIM: Increased resistance of Helicobacter pylori to antibiotics
      has increased the need to develop new first-line treatments for H. pylori. We
      have prospectively evaluated 10-day sequential versus conventional triple therapy
      in peptic ulcer patients. METHODS: One hundred and fifty-nine patients with
      peptic ulcer diseases were prospectively randomized to receive 10 days of
      lansoprazole, amoxicillin, and clarithromycin (conventional triple therapy) or 5
      days of lansoprazole and amoxicillin followed by 5 days of lansoprazole,
      clarithromycin, and metronidazole (sequential therapy). Post-treatment H. pylori
      status was determined by the (13) C-urea breath test. Eradication rates,
      antibiotic resistance rates by agar dilution method, drug compliance, and side
      effects were compared. RESULTS: The intention-to-treat eradication rates were
      75.9% (95% CI 66.5-85.3%, 60/79) in the sequential therapy group and 58.7% (95%
      CI 47.9-69.5%, 47/80) in the conventional triple therapy group (P = 0.01), while
      the per-protocol eradication rates were 86.8% (95% CI 78.7-94.8%, 59/68) and
      67.6% (95% CI 56.5-78.7%, 46/68) (P = 0.01), respectively. Compliance and side
      effects were similar in the two groups. Culture of H. pylori showed that 18.2%
      were resistant to clarithromycin, 41.9% to metronidazole. Dual resistance to both
      antibiotics was 9.6%. CONCLUSIONS: Although 10-day sequential therapy yielded a
      higher H. pylori eradication rate than 10-day conventional triple therapy, the
      sequential therapy protocol did not result in a sufficiently satisfactory
      eradication rate. This might be related to the higher antibiotics resistance rate
      especially to dual resistance. More effective regimens are needed to overcome
      antibiotic resistance in Korea.

PMID- 22849547
TI  - Acute oral toxicity of Polyalthia longifolia var. pendula leaf extract in Wistar
      albino rats.
AB  - CONTEXT: Polyalthia longifolia (Sonn.) Thw. var. pendula (Annonaceae), a tall
      evergreen tree, is cultivated all over India. The plant is used in traditional
      systems of medicine for the treatment of fever, skin diseases, and hypertension.
      OBJECTIVE: The present study evaluated the acute oral toxicity of Polyalthia
      longifolia var. pendula leaf extract in Wistar albino rats. MATERIAL AND METHODS:
      The parameters evaluated daily after oral drug administration of the extract
      (540, 1080, 2160 and 3240 mg/kg body weight) were mortality, signs of toxicity,
      feed and water consumption and body weight changes up to 14 days. The effect of
      different doses of the extract on organ weight, biochemical and hematological
      parameters were evaluated on the 15th day. RESULTS AND CONCLUSION: Methanol
      extract of Polyalthia longifolia leaf up to the dose level 3240 mg/kg body weight
      did not produce any toxic effects or deaths; the extract was well tolerated by
      the rats. It did not alter body weight, feed and water consumption. The organ
      weight, biochemical and hematological analysis did not show any dose-dependent
      changes in any of the parameters examined in animals of both sexes. The acute
      oral administration of the methanol extract of Polyalthia longifolia leaf was not
      toxic and safe in a single dose.

PMID- 22849548
TI  - Malachite green toxicity and effects on reproductive success in zebrafish Danio
      rerio.
AB  - Malachite green (MG) is frequently used to treat fish pathogens in zebrafish, but
      little is known about how MG may affect the physiological processes that are
      targets of research investigations. This study evaluated the effects of MG on
      reproductive success in zebrafish, Danio rerio, and the relative toxicity of MG
      oxalate and MG chloride salts. After 5-day exposure to a prophylactic
      concentration (0.065 mg/L) of MG oxalate, the percentage of spawning pairs
      significantly declined (57.5%+/-8.5 SE) and then returned to pre-exposure levels
      (89%+/-6.6 SE) within one week. Embryo and larval survival were not affected by
      exposure of parents to MG; however, when exposed directly, MG oxalate was more
      toxic than MG chloride in both life stages. The LC(50) for embryos was 0.067 MUM
      and 0.116 MUM for MG oxalate and MG chloride, respectively, and the LC(50) for
      larvae, 0.057 MUM and 0.103 MUM, respectively. Other than a transient reduction
      in the number of fish that spawned, MG treatment of broodstock did not impact
      reproductive success, which indicates that MG can be used prophylactically with
      minimal effects on reproduction. Based on acute toxicity, MG chloride should be
      preferred over MG oxalate.

PMID- 22849549
TI  - Complementary and alternative medicine in the undergraduate medical curriculum: a
      survey of Korean medical schools.
AB  - BACKGROUND: The current status of complementary and alternative medicine (CAM)
      education in Korean medical schools is still largely unknown, despite a growing
      need for a CAM component in medical education. The prevalence, scope, and
      diversity of CAM courses in Korean medical school education were evaluated.
      DESIGN: Participants included academic or curriculum deans and faculty at each of
      the 41 Korean medical schools. A mail survey was conducted from 2007 to 2010.
      Replies were received from all 41 schools. RESULTS: CAM was officially taught at
      35 schools (85.4%), and 32 schools (91.4%) provided academic credit for CAM
      courses. The most common courses were introduction to CAM or integrative medicine
      (88.6%), traditional Korean medicine (57.1%), homeopathy and naturopathy (31.4%),
      and acupuncture (28.6%). Educational formats included lectures by professors and
      lectures and/or demonstrations by practitioners. The value order of core
      competencies was attitude (40/41), knowledge (32/41), and skill (6/41). Reasons
      for not initiating a CAM curriculum were a non-evidence-based approach in
      assessing the efficacy of CAM, insufficiently reliable reference resources, and
      insufficient time to educate students in CAM. CONCLUSIONS: This survey reveals
      heterogeneity in the content, format, and requirements among CAM courses at
      Korean medical schools. Korean medical school students should be instructed in
      CAM with a more consistent educational approach to help patients who participate
      in or demand CAM.

PMID- 22849550
TI  - Superionic conductivity in lithium-rich anti-perovskites.
AB  - Lithium ion batteries have shown great promise in electrical energy storage with
      enhanced energy density, power capacity, charge-discharge rates, and cycling
      lifetimes. However common fluid electrolytes consisting of lithium salts
      dissolved in solvents are toxic, corrosive, or flammable. Solid electrolytes with
      superionic conductivity can avoid those shortcomings and work with a metallic
      lithium anode, thereby allowing much higher energy densities. Here we present a
      novel class of solid electrolytes with three-dimensional conducting pathways
      based on lithium-rich anti-perovskites (LiRAP) with ionic conductivity of sigma >
      10(-3) S/cm at room temperature and activation energy of 0.2-0.3 eV. As
      temperature approaches the melting point, the ionic conductivity of the anti
      perovskites increases to advanced superionic conductivity of sigma > 10(-2) S/cm
      and beyond. The new crystalline materials can be readily manipulated via
      chemical, electronic, and structural means to boost ionic transport and serve as
      high-performance solid electrolytes for superionic Li(+) conduction in
      electrochemistry applications.

PMID- 22849552
TI  - Organocatalytic synthesis of quinine-functionalized poly(carbonate)s.
AB  - The ring-opening polymerization of substituted cyclic carbonates with 1-(3,5-bis
      trifluoromethyl-phenyl)-3-cyclohexyl-thiourea (TU)/1,8-diazabicyclo[5.4.0]undec-7
      ene (DBU) organocatalysts afford highly functionalized oligocarbonates. The
      fluorescent alkaloid quinine can be readily incorporated into the oligocarbonates
      either by initiation from quinine or by ring-opening polymerization of a quinine
      functionalized cyclic carbonate (MTC-Q). Copolymerization of MTC-Q with a boc
      protected guanidinium cyclic carbonate affords, after deprotection, highly water
      soluble cationic copolymers functionalized with both quinine and pendant
      guanidinium groups. When multiple quinine groups are attached to the oligomers,
      they exhibit minimal fluorescence due to self-quenching. Upon hydrolysis, the
      fluorescence intensity increases, providing a potential strategy for monitoring
      the hydrolysis rates in real time.

PMID- 22849551
TI  - Demography and speciation history of the homoploid hybrid pine Pinus densata on
      the Tibetan Plateau.
AB  - Pinus densata is an ecologically successful homoploid hybrid that inhabits vast
      areas of heterogeneous terrain on the south-eastern Tibetan Plateau as a result
      of multiple waves of colonization. Its region of origin, route of colonization
      onto the plateau and the directions of introgression with its parental species
      have previously been defined, but little is known about the isolation and
      divergence history of its populations. In this study, we surveyed nucleotide
      polymorphism over eight nuclear loci in 19 representative populations of P.
      densata and its parental species. Using this information and coalescence
      simulations, we assessed the historical changes in its population size, gene flow
      and divergence in time and space. The results indicate a late Miocene origin for
      P. densata associated with the recent uplift of south-eastern Tibet. The
      subsequent differentiation between geographical regions of this species began in
      the late Pliocene and was induced by regional topographical changes and
      Pleistocene glaciations. The ancestral P. densata population had a large
      effective population size but the central and western populations were
      established by limited founders, suggesting that there were severe bottlenecks
      during the westward migration out of the ancestral hybrid zone. After separating
      from their ancestral populations, population expansion occurred in all
      geographical regions especially in the western range. Gene flow in P. densata was
      restricted to geographically neighbouring populations, resulting in significant
      differentiation between regional groups. The new information on the divergence
      and demographic history of P. densata reported herein enhances our understanding
      of its speciation process on the Tibetan Plateau.

PMID- 22849553
TI  - In vitro inhibitory effects of plant-based foods and their combinations on
      intestinal alpha-glucosidase and pancreatic alpha-amylase.
AB  - BACKGROUND: Plant-based foods have been used in traditional health systems to
      treat diabetes mellitus. The successful prevention of the onset of diabetes
      consists in controlling postprandial hyperglycemia by the inhibition of alpha
      glucosidase and pancreatic alpha-amylase activities, resulting in aggressive
      delay of carbohydrate digestion to absorbable monosaccharide. In this study, five
      plant-based foods were investigated for intestinal alpha-glucosidase and
      pancreatic alpha-amylase. The combined inhibitory effects of plant-based foods
      were also evaluated. Preliminary phytochemical analysis of plant-based foods was
      performed in order to determine the total phenolic and flavonoid content.
      METHODS: The dried plants of Hibiscus sabdariffa (Roselle), Chrysanthemum indicum
      (chrysanthemum), Morus alba (mulberry), Aegle marmelos (bael), and Clitoria
      ternatea (butterfly pea) were extracted with distilled water and dried using
      spray drying process. The dried extracts were determined for the total phenolic
      and flavonoid content by using Folin-Ciocateu's reagent and AlCl3 assay,
      respectively. The dried extract of plant-based food was further quantified with
      respect to intestinal alpha-glucosidase (maltase and sucrase) inhibition and
      pancreatic alpha-amylase inhibition by glucose oxidase method and
      dinitrosalicylic (DNS) reagent, respectively. RESULTS: The phytochemical analysis
      revealed that the total phenolic content of the dried extracts were in the range
      of 230.3-460.0 mg gallic acid equivalent/g dried extract. The dried extracts
      contained flavonoid in the range of 50.3-114.8 mg quercetin equivalent/g dried
      extract. It was noted that the IC50 values of chrysanthemum, mulberry and
      butterfly pea extracts were 4.24+/-0.12 mg/ml, 0.59+/-0.06 mg/ml, and 3.15+/-0.19
      mg/ml, respectively. In addition, the IC50 values of chrysanthemum, mulberry and
      butterfly pea extracts against intestinal sucrase were 3.85+/-0.41 mg/ml, 0.94+/
      0.11 mg/ml, and 4.41+/-0.15 mg/ml, respectively. Furthermore, the IC50 values of
      roselle and butterfly pea extracts against pancreatic alpha-amylase occurred at
      concentration of 3.52+/-0.15 mg/ml and 4.05+/-0.32 mg/ml, respectively. Combining
      roselle, chrysanthemum, and butterfly pea extracts with mulberry extract showed
      additive interaction on intestinal maltase inhibition. The results also
      demonstrated that the combination of chrysanthemum, mulberry, or bael extracts
      together with roselle extract produced synergistic inhibition, whereas roselle
      extract showed additive inhibition when combined with butterfly pea extract
      against pancreatic alpha-amylase. CONCLUSIONS: The present study presents data
      from five plant-based foods evaluating the intestinal alpha-glucosidase and
      pancreatic alpha-amylase inhibitory activities and their additive and synergistic
      interactions. These results could be useful for developing functional foods by
      combination of plant-based foods for treatment and prevention of diabetes
      mellitus.

PMID- 22849554
TI  - Bovine viral diarrhoea virus seroprevalence and vaccination usage in dairy and
      beef herds in the Republic of Ireland.
AB  - BACKGROUND: Bovine viral diarrhoea (BVD) is an infectious disease of cattle with
      a worldwide distribution. Herd-level prevalence varies among European Union (EU)
      member states, and prevalence information facilitates decision-making and
      monitoring of progress in control and eradication programmes. The primary
      objective of the present study was to address significant knowledge gaps
      regarding herd BVD seroprevalence (based on pooled sera) and control on Irish
      farms, including vaccine usage. METHODS: Preliminary validation of an indirect
      BVD antibody ELISA test (Svanova, Biotech AB, Uppsala, Sweden) using pooled sera
      was a novel and important aspect of the present study. Serum pools were
      constructed from serum samples of known seropositivity and pools were analysed
      using the same test in laboratory replicates. The output from this indirect ELISA
      was expressed as a percentage positivity (PP) value. Results were used to guide
      selection of a proposed cut-off (PCO) PP. This indirect ELISA was applied to
      randomly constructed within-herd serum pools, in a cross-sectional study of a
      stratified random sample of 1,171 Irish dairy and beef cow herds in 2009, for
      which vaccination status was determined by telephone survey. The herd-level
      prevalence of BVD in Ireland (percentage positive herds) was estimated in non
      vaccinating herds, where herds were classified positive when herd pool result
      exceeded PCO PP. Vaccinated herds were excluded because of the potential impact
      of vaccination on herd classification status. Comparison of herd-level
      classification was conducted in a subset of 111 non-vaccinating dairy herds using
      the same ELISA on bulk milk tank (BMT) samples. Associations between possible
      risk factors (herd size (quartiles)) and herd-level prevalence were determined
      using chi-squared analysis. RESULTS: Receiver Operating Characteristics Analysis
      of replicate results in the preliminary validation study yielded an optimal cut
      off PP (Proposed Cut-off percentage positivity - PCO PP) of 7.58%. This PCO PP
      gave a relative sensitivity (Se) and specificity (Sp) of 98.57% and 100%
      respectively, relative to the use of the ELISA on individual sera, and was chosen
      as the optimal cut-off since it resulted in maximization of the prevalence
      independent Youden's Index.The herd-level BVD prevalence in non-vaccinating herds
      was 98.7% (95% CI - 98.3-99.5%) in the cross-sectional study with no significant
      difference between dairy and beef herds (98.3% vs 98.8%, respectively, p =
      0.595).An agreement of 95.4% was found on Kappa analysis of herd serological
      classification when bulk milk and serum pool results were compared in non
      vaccinating herds. 19.2 percent of farmers used BVDV vaccine; 81% of vaccinated
      herds were dairy. A significant association was found between seroprevalence
      (quartiles) and herd size (quartiles) (p < 0.01), though no association was found
      between herd size (quartiles) and herd-level classification based on PCO (p =
      0.548). CONCLUSIONS: The results from this study indicate that the true herd
      level seroprevalence to Bovine Virus Diarrhoea (BVD) virus in Ireland is
      approaching 100%. The results of the present study will assist with national
      policy development, particularly with respect to the national BVD eradication
      programme which commenced recently.

PMID- 22849555
TI  - SymDex: increasing the efficiency of chemical fingerprint similarity searches for
      comparing large chemical libraries by using query set indexing.
AB  - The large sizes of today's chemical databases require efficient algorithms to
      perform similarity searches. It can be very time consuming to compare two large
      chemical databases. This paper seeks to build upon existing research efforts by
      describing a novel strategy for accelerating existing search algorithms for
      comparing large chemical collections. The quest for efficiency has focused on
      developing better indexing algorithms by creating heuristics for searching
      individual chemical against a chemical library by detecting and eliminating
      needless similarity calculations. For comparing two chemical collections, these
      algorithms simply execute searches for each chemical in the query set
      sequentially. The strategy presented in this paper achieves a speedup upon these
      algorithms by indexing the set of all query chemicals so redundant calculations
      that arise in the case of sequential searches are eliminated. We implement this
      novel algorithm by developing a similarity search program called Symmetric
      inDexing or SymDex. SymDex shows over a 232% maximum speedup compared to the
      state-of-the-art single query search algorithm over real data for various
      fingerprint lengths. Considerable speedup is even seen for batch searches where
      query set sizes are relatively small compared to typical database sizes. To the
      best of our knowledge, SymDex is the first search algorithm designed specifically
      for comparing chemical libraries. It can be adapted to most, if not all, existing
      indexing algorithms and shows potential for accelerating future similarity search
      algorithms for comparing chemical databases.

PMID- 22849556
TI  - Novel one-pot three-component coupling reaction with trimethylsilylmethyl
      phosphonate, acyl fluoride, and aldehyde through the Horner-Wadsworth-Emmons
      reaction.
AB  - A novel three-component coupling between trimethylsilylmethylphosphonate, acyl
      fluoride, and aldehyde has been developed. A sequential nucleophilic addition of
      lithio-trimethylsilylmethylphosphonate to the acyl fluoride and Horner-Wadsworth
      Emmons reaction of an aldehyde with the lithio-beta-ketophosphonate generated in
      situ by desilylation at the alpha-position of the alpha-silyl-beta
      ketophosphonate by fluoride took place cleanly in a one-pot operation. Various E-
      and Z-enones were obtained in high yields with high stereoselectivities by this
      one-pot procedure.

PMID- 22849557
TI  - Tissue-engineered allograft intervertebral disc transplantation for the treatment
      of degenerative disc disease: experimental study in a beagle model.
AB  - OBJECTIVES: To investigate whether the intervention of nucleus pulposus (NP)
      cells or human telomerase reverse transcriptase (hTERT) gene-transfected NP cells
      can prevent the degeneration process after allograft total disc transplantation.
      METHODS: Eighteen canine lumbar intervertebral discs were obtained from five
      canines and cryopreserved in liquid nitrogen. Canine nucleus pulposus cells were
      isolated and transduced with recombinant adeno-associated virus (rAAV)-hTERT. The
      cells were injected into the discs to construct a tissue-engineered allograft
      disc (group A). NP cells and DMEM/F12 were used for positive control (group B)
      and blank control (group C). 18 beagle dogs received the three groups of
      allograft intervertebral disc (IVD) composites implantation, respectively.
      Radiographic examinations were performed at 4, 8, and 12 weeks postimplantation.
      At 12 weeks after operation, all dogs were sacrificed and the lumbar spines were
      harvested for the biomechanical analysis, and then the allografts underwent
      histological analysis, ectogenic NP cell tracing, and hTERT mRNA analysis.
      RESULTS: Bony fusion between the intervertebral disc allograft and the adjacent
      host intervertebral body were observed in all animals. The disc height and T2
      signal intensity preservation in group A and B was better than group C. Magnetic
      resonance images (MRI) showed typical degenerative changes in group C. In group
      A, the normalized grayscale of the transplanted disc on MRI was significant
      higher compared with the controls at 12 weeks. A biomechanical test showed a poor
      stability preservation in group C compared to group A and B. PKH-26-positive
      cells were identified within the allograft discs in group A at 12 weeks,
      providing evidence of cell survival. Histological analysis showed the NP cell
      morphology, cell number, and distribution of the allograft discs was better
      preserved in group A and B compared to group C at a 12-week follow-up.
      CONCLUSION: The present study demonstrated that NP cells or hTERT-loaded NP cells
      intervention could effectively resist the degeneration of the allogenic
      transplanted intervertebral discs in a beagle model. The hTERT-loaded NP cells
      had a better antidegeneration effect on the transplanted disc than NP cells. This
      modified disc regeneration technique through NP cell injection or manipulation
      may have the potential to ensure the long-term function preservation of allograft
      disc transplantation.

PMID- 22849558
TI  - Partitioning of organic chemicals to storage lipids: elucidating the dependence
      on fatty acid composition and temperature.
AB  - Lipids serve as important compartments in partitioning of neutral organic
      chemicals into organisms. Storage lipids, made up of triglycerides with various
      fatty acids, are among the major classes of lipids. Here, we present experimental
      equilibrium partition data for diverse chemicals in fish oil, linseed oil, and
      goose fat at 37  degrees C. These data, in combination with data from the
      literature for olive oil and milk fat, show that the fatty acid composition of
      triglycerides has no significant influence on the partition coefficient. This
      result allows the derivation of a general predictive model for partitioning into
      storage lipids. We have collected storage lipid/water partition coefficients for
      247 compounds to calibrate polyparameter linear free energy relationships (pp
      LFERs) for 37  degrees C, which achieved a model fit with a root mean squared
      error of 0.20 log units. To extend the applicability of this model toward the
      aquatic food chain, we also measured fish oil partition data at 7  degrees C. The
      resulting enthalpies were used to calibrate an additional pp-LFER for the
      temperature dependence of storage lipid/water partitioning. This model allows us
      to estimate partition coefficients at desired temperatures that occur under
      typical ambient conditions.

PMID- 22849559
TI  - Peri-operative chemotherapy in the management of resectable colorectal cancer
      pulmonary metastases.
AB  - BACKGROUND: Surgery is often advocated in patients with resectable pulmonary
      metastases from colorectal cancer (CRC). Our study aims to evaluate peri
      operative chemotherapy in patients with metastastic CRC undergoing pulmonary
      metastasectomy. METHODS: Patients treated for CRC who underwent pulmonary
      metastasectomy by a single surgeon were identified. Outcome measures included
      survival, peri-operative complications, radiological and histological evidence of
      chemotherapy-induced lung toxicities. RESULTS: Between 1997 and 2009, 51 eligible
      patients were identified undergoing a total of 72 pulmonary resections. Thirty
      eight patients received peri-operative chemotherapy, of whom 9 received an
      additional biological agent. Five-year overall survival rate was 72% in the whole
      cohort - 74% and 68% in those who received peri-operative chemotherapy (CS) and
      those who underwent surgery alone (S) respectively. Five-year relapse free
      survival rate was 31% in the whole cohort - 38% and <=18% in CS and S groups
      respectively. Only 8% had disease progression during neoadjuvant chemotherapy.
      There were no post-operative deaths. Surgical complications occurred in only 4%
      of patients who received pre-operative chemotherapy. There was neither
      radiological nor histological evidence of lung toxicity in resected surgical
      specimens. CONCLUSIONS: Peri-operative chemotherapy can be safely delivered to
      CRC patients undergoing pulmonary metastasectomy. Survival in this selected group
      of patients was favourable.

PMID- 22849560
TI  - Gallic acid induces the apoptosis of human osteosarcoma cells in vitro and in
      vivo via the regulation of mitogen-activated protein kinase pathways.
AB  - To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human
      osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to
      cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors
      were established in nude BALB/c mice to evaluate the anticancer capacity of GA in
      vivo. The results showed that GA inhibited the proliferation and induced the
      apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38
      activation and the downregulation of c-Jun N-terminal kinase (JNK) and
      extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK
      inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas
      JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth
      inhibition. In vivo studies further showed that GA administration decreased
      xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis
      demonstrated the downregulation of PCNA and CD31 expression and upregulation of
      apoptosis in MNNG/HOS tumor tissues following GA treatment. This study
      demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by
      the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings
      suggest that GA could be a potent agent for osteosarcoma intervention.

PMID- 22849561
TI  - Sequence mining and transcript profiling to explore differentially expressed
      genes associated with lipid biosynthesis during soybean seed development.
AB  - BACKGROUND: Soybean (Glycine max L.) is one of the most important oil crops in
      the world. It is desirable to increase oil yields from soybean, and so this has
      been a major goal of oilseed engineering. However, it is still uncertain how many
      genes and which genes are involved in lipid biosynthesis. RESULTS: Here, we
      evaluated changes in gene expression over the course of seed development using
      Illumina (formerly Solexa) RNA-sequencing. Tissues at 15 days after flowering
      (DAF) served as the control, and a total of 11592, 16594, and 16255
      differentially expressed unigenes were identified at 35, 55, and 65 DAF,
      respectively. Gene Ontology analyses detected 113 co-expressed unigenes
      associated with lipid biosynthesis. Of these, 15 showed significant changes in
      expression levels (log2fold values >= 1) during seed development. Pathway
      analysis revealed 24 co-expressed transcripts involved in lipid biosynthesis and
      fatty acid biosynthesis pathways. We selected 12 differentially expressed genes
      and analyzed their expressions using qRT-PCR. The results were consistent with
      those obtained from Solexa sequencing. CONCLUSION: These results provide a
      comprehensive molecular biology background for research on soybean seed
      development, particularly with respect to the process of oil accumulation. All of
      the genes identified in our research have significance for breeding soybeans with
      increased oil contents.

PMID- 22849562
TI  - Statin use and the risk of bladder cancer: a population-based case-control study.
AB  - OBJECTIVE: The aim of this study was to investigate whether the use of statins is
      associated with bladder cancer risk. METHODS: The authors conducted a population
      based case-control study in Taiwan. Cases consisted of all patients who were aged
      50 years and older and had a first-time diagnosis of bladder cancer, for the
      period between 2004 and 2010. The controls were matched to cases by age, sex and
      index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were
      estimated by using multiple logistic regression. RESULTS: The authors examined
      325 bladder cancer cases and 1300 controls. The unadjusted ORs for any statin
      prescription was 0.94 (95% CI 0.70 - 1.28) and the adjusted OR was 0.88 (95% CI
      0.61 - 1.25). Compared with no use of statins, the adjusted ORs were 0.72 (95% CI
      0.40 - 1.28) for the group having been prescribed statins with cumulative defined
      daily dose (DDDs) below 56 DDDs, 0.81 (95% CI 0.46 - 1.43) for the group with
      cumulative dose between 56 DDDs and 196 DDDs, and 1.11 (95% CI 0.67 - 1.85) for
      the group with cumulative statin use of 196 DDDs or more. CONCLUSIONS: The
      present data do not provide evidence to support either beneficial or harmful
      associations between statin use and bladder cancer risk.

PMID- 22849565
TI  - Potential of Moringa oleifera root and Citrus sinensis fruit rind extracts in the
      treatment of ulcerative colitis in mice.
AB  - CONTEXT: The plant Moringa oleifera Lam (Moringaceae), commonly known as the
      drumstick tree, is an indigenous species in India. This species has been of
      interest to researchers because traditionally its roots are reported in the
      treatment of ulcerative colitis (UC). Traditionally it is reported that Citrus
      sinensis Linn (Rutaceae) fruit rind when combined with M. oleifera will increase
      the efficacy of the plant in the treatment of UC. OBJECTIVE: The present work was
      undertaken to determine the effectiveness of M. oleifera root alone and in
      combination with C. sinensis fruit rind in the treatment of UC. MATERIALS AND
      METHODS: Ethanol and aqueous extracts of M. oleifera roots (100 and 200 mg/kg,
      body weight) were screened alone and in equal combination with ethanol extract of
      C. sinensis fruit rind, i.e., 50 mg/kg each of C. sinensis and M. oleifera for
      their activity on acetic acid-induced UC in mice. RESULTS: Treatment with
      combination of extracts of M. oleifera root and C. sinensis fruit rind (50 mg/kg,
      each) showed less ulceration and hyperemia than individual extract (200 mg/kg) in
      histopathological observation. Acetic acid increased myeloperoxidase (MPO) level
      in blood and colon tissue to 342 U/mL and 384 U/mg, respectively. Combination of
      ethanol extract of M. oleifera root with C. sinensis fruit rind extract
      significantly (p<0.05) decreased MPO in blood and tissue to 278 U/mL and 291
      U/mg, respectively. MPO in blood and tissue in control group was 85 +/- 1.2 U/mL
      and 96 +/- 1.3 U/mg, respectively. Similarly this combination significantly
      reduced malondialdehyde (MDA) level in blood and tissue to 7.11 nmol/mL and 8.19
      nmol/mg, from 11.20 nmol/mL and 13.20 nmol/mg, respectively. MDA in blood and
      tissue in control group was 2.76 +/- 1.2 nmol/mL and 3.76 +/- 1.2 nmol/mg,
      respectively. DISCUSSION AND CONCLUSION: Results show that a combination of M.
      oleifera root extracts with C. sinensis fruit rind extract is effective in the
      treatment of UC and results are comparable with the standard drug prednisolone.

PMID- 22849563
TI  - Benefits of oral Polypodium Leucotomos extract in MM high-risk patients.
AB  - BACKGROUND: UV radiation and the presence of melanocytic nevi are the main risk
      factors of sporadic melanoma (MM). Protection of skin by an oral photoprotective
      agent would have substantial benefits. OBJECTIVE: We investigated the possible
      role of an oral Polypodium leucotomos (PL) extract to improve systemic
      photoprotection in patients at risk of skin cancer analyzing the ability to
      decrease UV-induced erythema. We also studied the interaction among MC1R
      polymorphisms and CDKN2A status with the minimal erythematous dose (MED) and
      their influence in the response after oral PL. METHODS: A total of 61 patients
      (25 with familial and/or multiple MM, 20 with sporadic MM and 16 with atypical
      mole syndrome without history of MM) were exposed to varying doses of artificial
      UVB radiation without and after oral administration of a total dose of 1080 mg of
      PL. RESULTS: Oral PL treatment significantly increased the MED mean in all group
      patients (0.123 to 0.161 J/cm(2) , p<0.05). Although not significant, we noticed
      a stronger effect of PL on the MED of patients with familial MM compared to those
      with MM (U=273, p=0.06). Among the patients with familial MM, those exhibiting a
      mutated CDKN2A and/or polymorphisms in MC1R had the bigger differences in
      response to treatment with PL. LIMITATIONS: Reduced number of patients. No
      control population. CONCLUSIONS: Administration of PL leads to a significant
      reduction of sensitivity to UVR (p<0.05) in all patients. Dark-eye patients and
      patients with higher UVR sensibility (lower basal MED) would be the most
      benefited from oral PL treatment.

PMID- 22849566
TI  - Trichoblastic carcinoma associated with multiple familial trichoepithelioma.

PMID- 22849567
TI  - Asymmetric adaptation to indolic and aliphatic glucosinolates in the B and Q
      sibling species of Bemisia tabaci (Hemiptera: Aleyrodidae).
AB  - The role glucosinolates play in defending plants against phloem feeders such as
      aphids and whiteflies is currently not clear as these herbivores may avoid
      bringing glucosinolates from the phloem sap into contact with myrosinase enzymes.
      Here, we investigated the effects of high levels of aliphatic and indolic
      glucosinolates on life history traits and detoxification gene expression in two
      sibling species, B and Q, of the whitefly Bemisia tabaci. High levels of
      aliphatic glucosinolates decreased the average oviposition rate of both species
      and reduced the survival and developmental rate of Q nymphs. High levels of
      indolic glucosinolates decreased the oviposition rate and survival of nymphal
      stages of the B species and the developmental rate of both species. Molecular
      analyses revealed two major asymmetries between the B and Q species. First,
      specific GST genes (BtGST1 and BtGST2) were significantly induced during exposure
      to indolic glucosinolates only in Q. This may reflect the genes putative
      involvement in indolic glucosinolates detoxification and explain the species'
      good performance on plants accumulating indolic glucosinolates. Second, the
      constitutive expression of eight of the 10 detoxification genes analysed was
      higher in the Q species than in the B species. Interestingly, four of these genes
      were induced in B in response to high levels of glucosinolates. It seems,
      therefore, that the B and Q species differ in their 'optimal defence strategy'. B
      utilizes inducible defences that are profitable if the probability of
      experiencing the stress is small and its severity is low, while Q invests
      significant resources in being always 'ready' for a challenge.

PMID- 22849568
TI  - A graphene-based sensor array for high-precision and adaptive target
      identification with ensemble aptamers.
AB  - In this work, we report a new concept of adaptive "ensemble aptamers"
      (ENSaptamers) that exploits the collective recognition abilities of a small set
      of rationally designed, nonspecific DNA sequences to identify molecular or
      cellular targets discriminatively. In contrast to in vitro-selected aptamers,
      which possess specific "lock-and-key" recognition, ENSaptamers rely on pattern
      recognition that mimics natural olfactory or gustatory systems. Nanographene
      oxide was employed to provide a low-background and highly reproducible
      fluorescent assay system. We demonstrate that this platform provides a highly
      discriminative and adaptive tool for high-precision identification of a wide
      range of targets for diagnostic and proteomic applications with a nearly
      unlimited supply of ENSaptamer receptors.

PMID- 22849569
TI  - Increased expression of the homologue of enhancer-of-split 1 protects neurons
      from beta amyloid neurotoxicity and hints at an alternative role for transforming
      growth factor beta1 as a neuroprotector.
AB  - INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by the deposition of beta-amyloid (Abeta) in the brain, which
      produces progressive neuronal loss and dementia. We recently demonstrated that
      the noxious effects of Abeta on cultured hippocampal neurons are in part provoked
      by the antagonism of nerve growth factor (NGF) signalling, which impairs the
      activation of nuclear factor kappaB (NF-kappaB) by impeding the tyrosine
      phosphorylation of I-kappaBalpha. As a result, the expression of the homologue of
      Enhancer-of split 1 (Hes1) gene is downregulated and ultimately, gamma
      aminobutyric acid (GABA)-ergic connectivity is lost. METHODS: Hes1 activity was
      promoted in cultured hippocampal neurons by overexpressing a Hes1-encoding
      plasmid or by upregulating this gene by activating NF-kappaB through different
      approaches (overexpressing either the I-kappaB kinasebeta, or p65/RelA/NF
      kappaB). Alternatively neurons were exposed to TGFbeta1. Dendrite patterning,
      GABAergic connectivity and cell survival were analyzed by immunofluorescence
      microscopy. Hes1 expression was determined by real-time PCR. NF-kappaB activation
      was measured using the dual-luciferase reporter assay. RESULTS: The expression of
      Hes1 abolished the effects of Abeta on dendritic patterning and GABAergic input,
      and it prevented the death of the cultured neurons. TGFbeta1, a known
      neuroprotector, could counteract the deleterious effects of Abeta by inducing NF
      kappaB activation following the serine phosphorylation of I-kappaBalpha. Indeed,
      the number of GABAergic terminals generated by inducing Hes1 expression was
      doubled. CONCLUSION: Our data define some of the mechanisms involved in Abeta
      mediated cell death and they point to potential means to counteract this noxious
      activity.

PMID- 22849570
TI  - Two synchronous periungual BCC treated with Mohs surgery. Nail polish related?
AB  - Basal cell carcinoma (BCC), the most frequent malignant skin tumor observed in
      Caucasian adults, especially males, occurs mainly in sun-exposed areas of the
      body. BCC in the periungual tissues, such as proximal nail fold, nail matrix,
      nail bed and hyponychium, is rarely reported. We report a patient with two
      synchronous BCC of the periungual tissue localized in the IV and V fingernail,
      effectively treated with Mohs micrographic surgery.

PMID- 22849571
TI  - Cascade carbopalladation reaction between alkynes and gem-dibromoolefins: facile
      access to monoannelated pentalenes.
AB  - A carbopalladation cascade reaction of easily accessible gem-dibromoolefins and
      alkynes furnishes monobenzo- and mononaphthopentalenes. The new chromophores
      accessed by this short route exhibit small HOMO-LUMO gaps and redox amphoteric
      behavior with tunable redox potentials.

PMID- 22849572
TI  - The Arabidopsis apyrase AtAPY1 is localized in the Golgi instead of the
      extracellular space.
AB  - BACKGROUND: The two highly similar Arabidopsis apyrases AtAPY1 and AtAPY2 were
      previously shown to be involved in plant growth and development, evidently by
      regulating extracellular ATP signals. The subcellular localization of AtAPY1 was
      investigated to corroborate an extracellular function. RESULTS: Transgenic
      Arabidopsis lines expressing AtAPY1 fused to the SNAP-(O(6)-alkylguanine-DNA
      alkyltransferase)-tag were used for indirect immunofluorescence and AtAPY1 was
      detected in punctate structures within the cell. The same signal pattern was
      found in seedlings stably overexpressing AtAPY1-GFP by indirect
      immunofluorescence and live imaging. In order to identify the nature of the
      AtAPY1-positive structures, AtAPY1-GFP expressing seedlings were treated with the
      endocytic marker stain FM4-64 (N-(3-triethylammoniumpropyl)-4-(p
      diethylaminophenyl-hexatrienyl)-pyridinium dibromide) and crossed with a
      transgenic line expressing the trans-Golgi marker Rab E1d. Neither FM4-64 nor Rab
      E1d co-localized with AtAPY1. However, live imaging of transgenic Arabidopsis
      lines expressing AtAPY1-GFP and either the fluorescent protein-tagged Golgi
      marker Membrin 12, Syntaxin of plants 32 or Golgi transport 1 protein homolog
      showed co-localization. The Golgi localization was confirmed by immunogold
      labeling of AtAPY1-GFP. There was no indication of extracellular AtAPY1 by
      indirect immunofluorescence using antibodies against SNAP and GFP, live imaging
      of AtAPY1-GFP and immunogold labeling of AtAPY1-GFP. Activity assays with AtAPY1
      GFP revealed GDP, UDP and IDP as substrates, but neither ATP nor ADP. To
      determine if AtAPY1 is a soluble or membrane protein, microsomal membranes were
      isolated and treated with various solubilizing agents. Only SDS and urea (not
      alkaline or high salt conditions) were able to release the AtAPY1 protein from
      microsomal membranes. CONCLUSIONS: AtAPY1 is an integral Golgi protein with the
      substrate specificity typical for Golgi apyrases. It is therefore not likely to
      regulate extracellular nucleotide signals as previously thought. We propose
      instead that AtAPY1 exerts its growth and developmental effects by possibly
      regulating glycosylation reactions in the Golgi.

PMID- 22849574
TI  - A platelet-rich plasma-based membrane as a periosteal substitute with enhanced
      osteogenic and angiogenic properties: a new concept for bone repair.
AB  - The periosteum plays a pivotal role during bone development and repair
      contributing to bone vascularization and osteoprogenitor cells source. We propose
      a periosteal substitute engineered using a platelet-rich plasma (PRP) membrane
      incorporating autologous bone marrow-derived mesenchymal stem cells (PRP/BMSC gel
      membrane) to be wrapped around an osteoconductive scaffold for regeneration of
      compromised bone defects. The PRP/BMSC gel membrane was optimized using different
      compositions for optimal release of vascular endothelial growth factor (VEGF) and
      platelet derived growth factor-BB (PDGF-BB). Survival and proliferation of cells
      in the PRP gel membrane with time were confirmed in addition to their osteogenic
      capacity. Furthermore, to evaluate the possible effects of the PRP/BMSC gel
      membrane on surrounding progenitor cells in the injury area, we found that the
      PRP gel membrane products could significantly induce the migration of human
      endothelial cells in vitro, and increased the expression of bone morphogenetic
      protein 2 in cultured BMSC. These cells also secreted significant amounts of
      soluble proangiogenic factors, such as PDGF-BB, VEGF, and interleukin-8 (IL-8).
      Finally, the functionality of the PRP/BMSC gel membrane periosteal substitute for
      bone regeneration was tested in vivo both in an ectopic mouse model as well as in
      a rabbit segmental bone defect model providing evidence of its capacity to
      biomimic a periosteal response enhancing bone regeneration.

PMID- 22849573
TI  - Protective effect of cactus cladode extract against cisplatin induced oxidative
      stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical
      composition.
AB  - BACKGROUND: Cis-Platinum (II) (cis-diammine dichloroplatinum; CDDP) is a potent
      antitumor compound widely used for the treatment of many malignancies. An
      important side-effect of CDDP is nephrotoxicity. The cytotoxic action of this
      drug is often thought to induce oxidative stress and be associated with its
      ability to bind DNA to form CDDP-DNA adducts and apoptosis in kidney cells. In
      this study, the protective effect of cactus cladode extract (CCE) against CDDP
      induced oxidative stress and genotoxicity were investigated in mice. We also
      looked for levels of malondialdehyde (MDA), catalase activity, superoxide
      dismutase (SOD) activity, chromosome aberrations (CA) test, SOS Chromotest,
      expressions of p53, bax and bcl2 in kidney and we also analyzed several
      parameters of renal function markers toxicity such as serum biochemical analysis.
      METHODS: Adult, healthy balb/c (20-25 g) male mice aged of 4-5 weeks were pre
      treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks.
      Control animals were treated 3 days a week for 4 weeks by intraperitonial
      administration of 100 MUg/Kg.b.w CDDP. Animals which treated by CDDP and CCE were
      divided into two groups: the first group was administrated CCE 2 hours before
      each treatment with CDDP 3 days a week for 4 weeks. The second group was
      administrated without pre-treatment with CCE but this extract was administrated
      24 hours after each treatment with CDDP 3 days a week for 4 weeks. RESULTS: Our
      results showed that CDDP induced significant alterations in all tested oxidative
      stress markers. In addition it induced CA in bone morrow cells, increased the
      expression of pro-apoptotic proteins p53 and bax and decreased the expression of
      anti-apoptotic protein bcl2 in kidney. On the other hand, CDDP significantly
      increased the levels of urea and creatinine and decreased the levels of albumin
      and total protein.The treatment of CCE before or after treatment with CDDP
      showed, (i) a total reduction of CDDP induced oxidative damage for all tested
      markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of
      chromosomal aberrations compared to the group treated with CDDP alone (iii)
      restriction of the effect of CDDP by differential modulation of the expression of
      p53 which is decreased as well as its associated genes such as bax and bcl2,
      (iiii) restriction of serums levels of creatinine, urea, albumin and total
      protein resuming its values towards near normal levels of control. CONCLUSION: We
      concluded that CCE is beneficial in CDDP-induced kidney dysfunction in mice via
      its anti-oxidant anti-genotoxic and anti-apoptotic properties against CDDP.

PMID- 22849575
TI  - Selective separation of water, methanol, and ethanol by a porous coordination
      polymer built with a flexible tetrahedral ligand.
AB  - A novel porous coordination polymer, Cu(II)(mtpm)Cl(2) [mtpm = tetrakis(m
      pyridyloxy methylene)methane], has been synthesized, and its crystal structure
      has been determined. Its adsorption isotherms for water, methanol, and ethanol
      are totally different from each other. It adsorbs water at low humidity and shows
      gate-open behavior for methanol, but it does not adsorb ethanol. This compound
      has the capacity to separate both methanol and water from bioethanol, which is a
      mixture of water, methanol, and ethanol.

PMID- 22849576
TI  - The chiral herbicide beflubutamid (I): Isolation of pure enantiomers by HPLC,
      herbicidal activity of enantiomers, and analysis by enantioselective GC-MS.
AB  - For many chiral pesticides, little information is available on the properties and
      fate of individual stereoisomers. A basic data set would, first of all, include
      stereoisomer-specific analytical methods and data on the biological activity of
      stereoisomers. The herbicide beflubutamid, which acts as an inhibitor of
      carotenoid biosynthesis, is currently marketed as racemate against dicotyledonous
      weeds in cereals. Here, we present analytical methods for enantiomer separation
      of beflubutamid and two metabolites based on chiral HPLC. These methods were used
      to assign the optical rotation and to prepare milligram quantities of the pure
      enantiomers for further characterization with respect to herbicidal activity. In
      addition, sensitive analytical methods were developed for enantiomer separation
      and quantification of beflubutamid and its metabolites at trace level, using
      chiral GC-MS. In miniaturized biotests with garden cress, (-)-beflubutamid showed
      at least 1000* higher herbicidal activity (EC50, 0.50 MUM) than (+)-beflubutamid,
      as determined by analysis of chlorophyll a in 5-day-old leaves. The agricultural
      use of enantiopure (-)-beflubutamid rather than the racemic compound may
      therefore be advantageous from an environmental perspective. In further biotests,
      the (+)-enantiomer of the phenoxybutanoic acid metabolite showed effects on root
      growth, possibly via an auxin-type mode of action, but at 100* higher
      concentrations than the structurally related herbicide (+)-mecoprop. 

PMID- 22849577
TI  - Elastin-like peptide amphiphiles form nanofibers with tunable length.
AB  - Peptide amphiphiles (PAs) self-assemble nanostructures with potential
      applications in drug delivery and tissue engineering. Some PAs share
      environmentally responsive behavior with their peptide components. Here we report
      a new type of PAs biologically inspired from human tropoelastin. Above a lower
      critical solution temperature (LCST), elastin-like polypeptides (ELPs) undergo a
      reversible inverse phase transition. Similar to other PAs, elastin-like PAs
      (ELPAs) assemble micelles with fiber-like nanostructures. Similar to ELPs, ELPAs
      have inverse phase transition behavior. Here we demonstrate control over the
      ELPAs fiber length and cellular uptake. In addition, we observed that both
      peptide assembly and nanofiber phase separation are accompanied by a distinctive
      secondary structure attributed primarily to a type-1 beta turn. We also
      demonstrate increased solubility of hydrophobic paclitaxel (PAX) in the presence
      of ELPAs. Due to their biodegradability, biocompatibility, and environmental
      responsiveness, elastin-inspired biopolymers are an emerging platform for drug
      and cell delivery; furthermore, the discovery of ELPAs may provide a new and
      useful approach to engineer these materials into stimuli-responsive gels and drug
      carriers.

PMID- 22849578
TI  - Preliminary study of the immunostimulating activity of an ayurvedic preparation,
      Kanakasava, on the splenic cells of BALB/c mice in vitro.
AB  - CONTEXT: Immunostimulant plays an important role to prevent infections when
      defensive capacity of body is impaired, commonly occur with aging, cancer,
      diabetes, and sepsis. Kanakasava (KNK) is a polyherbal ayurvedic preparation used
      since ancient times for the treatment of respiratory diseases and to improve
      immunity. OBJECTIVE: The present study evaluated the immunostimulating potential
      of KNK. MATERIALS AND METHODS: The immunostimulating activity of KNK was
      evaluated by measuring immunoglobulin M (IgM) production and splenocyte
      proliferation in vitro. BALB/c mice splenocytes were treated with 0, 0.25, 0.5,
      0.75, 1, 1.5, 2, 3, and 4% (v/v) of KNK, and the cells were subcultured at 37
      degrees C, humidified atmosphere containing 5% CO(2) for 120 h. The production of
      IgM in cultured supernatants were determined by an enzyme-linked immunosorbent
      assay (ELISA) and the proliferations of cells were measured by the 3-(4,5
      dimethylthiazol-2-y)-2,5-diphenylterazolium bromide (MTT) method. RESULTS AND
      DISCUSSION: KNK at the doses of 0.25, 0.5, 0.75, 1, and 1.5% (v/v) significantly
      augmented polyclonal IgM production (1.211, 1.260, 1.274, 1.180, and 1.028 ug/mL,
      respectively) compared to control (0.246 ug/mL). Similarly, the same doses
      stimulated the proliferation of splenocytes as well (Abs. 0.270, 0.281, 0.368,
      0.328, and 0.301, respectively, measured at 570 nm) compared to untreated cells
      (Abs. 0.137). The activity of KNK was not retarded by the treatment of cells with
      polymixin B. Thus, our results demonstrate that KNK possesses immunostimulating
      potential that acts through the induction of lymphocytes for proliferation and
      IgM production. CONCLUSION: KNK may be useful for strengthening immune responses
      in case of insufficient or impaired immunity.

PMID- 22849579
TI  - Sclerostin monoclonal antibodies on bone metabolism and fracture healing.
AB  - INTRODUCTION: The biological enhancement of fracture healing may prevent
      complications such as non-union and revision surgery. Sclerostin is produced by
      osteocytes and binds to the LRP5/6 receptor. This inhibits the Wnt signalling
      pathway and thereby reduces bone formation. AREAS COVERED: Targeted deletion of
      the sclerostin gene has been found to enhance bone formation and fracture healing
      in rodent models. A number of in vivo studies have investigated the effect of
      sclerostin antibody on bone density with promising results. It also has an
      ability to promote fracture healing, screw fixation and metaphyseal bone healing
      in vivo. Early clinical studies have also demonstrated that it can increase bone
      mineral density, whilst being safe and well tolerated by patients. EXPERT
      OPINION: The data support the further investigation of this agent for the
      promotion of fracture healing. We aim to review the current literature and
      present an update on the use of this agent to promote bone formation and healing.

PMID- 22849580
TI  - Impact of treatment with bevacizumab beyond disease progression: a randomized
      phase II study of docetaxel with or without bevacizumab after platinum-based
      chemotherapy plus bevacizumab in patients with advanced nonsquamous non-small
      cell lung cancer (WJOG 5910L).
AB  - BACKGROUND: Bevacizumab, a humanized antibody to vascular endothelial growth
      factor (VEGF), shows clinical activity against human cancer, with its addition to
      standard chemotherapy having been found to improve outcome in patients with
      advanced nonsquamous non-small cell lung cancer (NSCLC). However, there have been
      no evidence-based studies to support the continued use of bevacizumab beyond
      disease progression in such patients treated with the drug in first-line therapy.
      We have now designed a randomized phase II trial to examine the clinical benefit
      and safety of continued bevacizumab treatment in patients with advanced
      nonsquamous NSCLC whose disease has progressed after first-line treatment with
      bevacizumab plus a platinum-based doublet. METHODS/DESIGN: WJOG 5910L was
      designed as a multicenter, open-label, randomized, phase II trial by the West
      Japan Oncology Group of docetaxel (arm A) versus docetaxel plus bevacizumab (arm
      B) in patients with recurrent or metatstatic nonsquamous NSCLC whose disease has
      progressed after first-line treatment with bevacizumab plus a platinum-based
      doublet. Patients in arm A will receive docetaxel at 60 mg/m2 and those in arm B
      will receive docetaxel at 60 mg/m2 plus bevacizumab at 15 mg/kg, with each drug
      administered on day 1 every 21 days until progression or unacceptable toxicity.
      The primary endpoint of the study is progression-free survival, with secondary
      endpoints including response rate, overall survival, and safety, for patients
      treated in either arm. TRIAL REGISTRATION: UMIN (University Hospital Medical
      Information Network in Japan) 000004715.

PMID- 22849582
TI  - Identification of two stably expressed QTLs for fat content in rice (Oryza
      sativa).
AB  - Fat content (FC) is an important component of the nutritional quality of the rice
      (Oryza sativa L.) grain and a partial determinant of grain quality. Three FC QTLs
      were identified from an analysis of a set of rice 'Kasalath'/'Koshihikari'
      backcross inbred lines, which were grown in three independent environments. Two
      of these QTLs (qFC7.1 and qFC7.2) were located on chromosome 7, and they were
      detected in all three environments. The presence of qFC7.1 and qFC7.2 was further
      confirmed by testing a set of 'Kasalath' (donor) / 'Koshihikari' (recipient)
      chromosome segment substitution lines (CSSLs) across six environments. Both QTLs
      significantly increased grain FC and they might be involved in lipid metabolism.
      The two QTLs were stably expressed in a number of environments and populations,
      making them suitable candidates for the improvement of FC via marker assisted
      breeding.

PMID- 22849581
TI  - Polyanalgesic Consensus Conference--2012: recommendations to reduce morbidity and
      mortality in intrathecal drug delivery in the treatment of chronic pain.
AB  - INTRODUCTION: Targeted intrathecal drug infusion to treat moderate to severe
      chronic pain has become a standard part of treatment algorithms when more
      conservative options fail. This therapy is well established in the literature,
      has shown efficacy, and is an important tool for the treatment of both cancer and
      noncancer pain; however, it has become clear in recent years that intrathecal
      drug delivery is associated with risks for serious morbidity and mortality.
      METHODS: The Polyanalgesic Consensus Conference is a meeting of experienced
      implanting physicians who strive to improve care in those receiving implantable
      devices. Employing data generated through an extensive literature search combined
      with clinical experience, this work group formulated recommendations regarding
      awareness, education, and mitigation of the morbidity and mortality associated
      with intrathecal therapy to establish best practices for targeted intrathecal
      drug delivery systems. RESULTS: Best practices for improved patient care and
      outcomes with targeted intrathecal infusion are recommended to minimize the risk
      of morbidity and mortality. Areas of focus include respiratory depression,
      infection, granuloma, device-related complications, endocrinopathies, and human
      error. Specific guidance is given with each of these issues and the general use
      of the therapy. CONCLUSIONS: Targeted intrathecal drug delivery systems are
      associated with risks for morbidity and mortality that can be devastating. The
      panel has given guidance to treating physicians and healthcare providers to
      reduce the incidence of these problems and to improve outcomes when problems
      occur.

PMID- 22849583
TI  - Study of the total synthesis of (-)-exiguolide.
AB  - In this article, we disclose the various routes and strategies we had to explore
      before finally achieving the total synthesis of (-)-exiguolide ((-)-1). Two first
      types of approaches were set, both relying on the Trost's domino ene-yne
      coupling/oxa-Michael reaction that we choose for its ability to control the
      geometry of the methylacrylate-bearing tetrahydropyrane ring B. In our first
      approach, we expected to assemble the two main fragments (C14-C21 and C1-C13) by
      creating the C13-C14 bond through a palladium(0)-catalyzed cross-coupling, but
      this step failed, unfortunately. In the second approach, which was more linear,
      we created the C16-C17 bond through condensation of a lithium acetylide on a
      Weinreb amide, and we assembled the C1-C5 and C6-C21 subunits through Trost's
      domino ene-yne coupling/oxa-Michael reaction. These two approaches served us to
      design an ameliorated third strategy, which finally led to the total synthesis of
      (-)-exiguolide.

PMID- 22849584
TI  - Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway.
AB  - INTRODUCTION: This study was performed to evaluate the attenuation of
      osteoarthritic (OA) pathogenesis via disruption of the stromal cell-derived
      factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling with AMD3100
      in a guinea pig OA model. METHODS: OA chondrocytes and cartilage explants were
      incubated with SDF-1, siRNA CXCR4, or anti-CXCR4 antibody before treatment with
      SDF-1. Matrix metalloproteases (MMPs) mRNA and protein levels were measured with
      real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA), respectively. The 35 9-month-old male Hartley guinea pigs (0.88 kg
      +/- 0.21 kg) were divided into three groups: AMD-treated group (n = 13); OA group
      (n = 11); and sham group (n = 11). At 3 months after treatment, knee joints,
      synovial fluid, and serum were collected for histologic and biochemical analysis.
      The severity of cartilage damage was assessed by using the modified Mankin score.
      The levels of SDF-1, glycosaminoglycans (GAGs), MMP-1, MMP-13, and interleukin-1
      (IL-1beta) were quantified with ELISA. RESULTS: SDF-1 infiltrated cartilage and
      decreased proteoglycan staining. Increased glycosaminoglycans and MMP-13 activity
      were found in the culture media in response to SDF-1 treatment. Disrupting the
      interaction between SDF-1 and CXCR4 with siRNA CXCR4 or CXCR4 antibody attenuated
      the effect of SDF-1. Safranin-O staining revealed less cartilage damage in the
      AMD3100-treated animals with the lowest Mankin score compared with the control
      animals. The levels of SDF-1, GAG, MMP1, MMP-13, and IL-1beta were much lower in
      the synovial fluid of the AMD3100 group than in that of control group.
      CONCLUSIONS: The binding of SDF-1 to CXCR4 induces OA cartilage degeneration. The
      catabolic processes can be disrupted by pharmacologic blockade of SDF-1/CXCR4
      signaling. Together, these findings raise the possibility that disruption of the
      SDF-1/CXCR4 signaling can be used as a therapeutic approach to attenuate
      cartilage degeneration.

PMID- 22849586
TI  - Preschool children with high adherence to inhaled corticosteroids for asthma do
      not show behavioural problems.
AB  - AIM: To assess prevalence of behavioural problems in preschool children with
      asthma with electronically verified exposure to inhaled corticosteroids (ICS).
      METHODS: Cross-sectional study of 81 children 2-5 years of age using daily ICS
      for persistent asthma. During 3 months' follow-up, adherence to ICS treatment was
      recorded by an electronical logging device (Smartinhaler((r))). Parents completed
      the Child Behavior Checklist 1.5-5 years (CBCL 1.5-5) to assess behavioural
      problems; results were compared to a published reference group of healthy
      children. RESULTS: The median (interquartile range) adherence to ICS was 92 (78
      97) %. There was no difference in total CBCL score between children with asthma
      on ICS (mean, [SD] 32.10 [1.99]) and the reference group (33.30 [1.87], 95% CI
      for difference -6.62 to 4.22). Children with asthma were more likely to have
      somatic complaints (95% CI for difference 0.64 to 1.96) and less likely to have
      anxious/depressive symptoms (95% CI for difference -1.57 to -0.25) than the
      reference group. CBCL scores were not significantly related to the electronically
      measured adherence rates. CONCLUSIONS: Maintenance treatment with ICS, taken
      daily as prescribed, is not associated with an increased risk of behavioural
      problems in preschool children.

PMID- 22849587
TI  - The effect of crystalloid versus medium molecular weight colloid solution on post
      operative nausea and vomiting after ambulatory gynecological surgery - a
      prospective randomized trial.
AB  - BACKGROUND: Intravenous fluid is recommended in international guidelines to
      improve patient post-operative symptoms, particularly nausea and vomiting. The
      optimum fluid regimen has not been established. This prospective, randomized,
      blinded study was designed to determine if administration of equivolumes of a
      colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting
      in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery
      compared to a crystalloid solution (Hartmann's Solution). METHODS: 120 patients
      were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60)
      intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1
      per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti
      emetic use, dizziness, sore throat, headache and subjective general well being at
      30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing
      was performed on a subgroup. RESULTS: At 2 hours the proportion of patients
      experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were
      increased in the colloid compared to crystalloid group respectively (1.49 +/- 0.3
      vs 0.68 +/- 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was
      low and did not differ between the groups. Sore throat, dizziness, headache and
      general well being were not different between the groups. A comparable reduction
      on post-operative FVC and FEV-1 and PEFR was observed in both groups.
      CONCLUSIONS: Intra-operative administration of colloid increased the incidence of
      early postoperative nausea and has no advantage over crystalloid for symptom
      control after gynaecological laparoscopic surgery.

PMID- 22849589
TI  - Asymmetric flow field-flow fractionation with multiangle light scattering
      detection for characterization of cellulose nanocrystals.
AB  - Cellulose nanocrystals (CNCs) were analyzed by asymmetric flow field-flow
      fractionation (AF4) coupled with multiangle light scattering (MALS) detection.
      Small fractions were collected from the output of the AF4 apparatus for
      investigation by transmission electron microscopy (TEM). The influence of CNC
      injection amount, the number of passes through a high-pressure homogenizer, and
      different CNC sources on the elution behavior and particle size distribution was
      investigated. The AF4-MALS results on crystal length were compared with those
      from TEM. Peak distortion and variation in elution profiles with the increase in
      sample load were observed. Good resolution was obtained when the injection mass
      varied from 20 to 40 MUg, corresponding to injections of 4-8 MUL at a starting
      concentration of ~5 MUg/MUL; concentrations during the separation process and at
      the detector were significantly lower. As the number of homogenization treatments
      increased, the peak shape became narrower and more symmetrical. This indicates a
      narrowed crystal length distribution, but regardless of source or homogenization
      treatment, no CNC preparation was as uniform as tobacco mosaic virus, a well
      known rigid rod model structure, whose length was found by AF4-MALS to be in
      agreement with literature values. CNCs derived from cotton contained longer
      crystals than those derived from microcrystalline cellulose, as shown by both AF4
      MALS and TEM techniques. An advantage of AF4-MALS compared to TEM is the ability
      to sample large numbers of rodlike particles, which is challenging and time
      consuming for TEM image analysis, especially without the presorting afforded by
      AF4. The good TMV results suggest a high degree of accuracy will pertain to the
      CNC size distribution measurements.

PMID- 22849588
TI  - Organosulfates as tracers for secondary organic aerosol (SOA) formation from 2
      methyl-3-buten-2-ol (MBO) in the atmosphere.
AB  - 2-Methyl-3-buten-2-ol (MBO) is an important biogenic volatile organic compound
      (BVOC) emitted by pine trees and a potential precursor of atmospheric secondary
      organic aerosol (SOA) in forested regions. In the present study, hydroxyl radical
      (OH)-initiated oxidation of MBO was examined in smog chambers under varied
      initial nitric oxide (NO) and aerosol acidity levels. Results indicate measurable
      SOA from MBO under low-NO conditions. Moreover, increasing aerosol acidity was
      found to enhance MBO SOA. Chemical characterization of laboratory-generated MBO
      SOA reveals that an organosulfate species (C(5)H(12)O(6)S, MW 200) formed and was
      substantially enhanced with elevated aerosol acidity. Ambient fine aerosol
      (PM(2.5)) samples collected from the BEARPEX campaign during 2007 and 2009, as
      well as from the BEACHON-RoMBAS campaign during 2011, were also analyzed. The MBO
      derived organosulfate characterized from laboratory-generated aerosol was
      observed in PM(2.5) collected from these campaigns, demonstrating that it is a
      molecular tracer for MBO-initiated SOA in the atmosphere. Furthermore, mass
      concentrations of the MBO-derived organosulfate are well correlated with MBO
      mixing ratio, temperature, and acidity in the field campaigns. Importantly, this
      compound accounted for an average of 0.25% and as high as 1% of the total organic
      aerosol mass during BEARPEX 2009. An epoxide intermediate generated under low-NO
      conditions is tentatively proposed to produce MBO SOA.

PMID- 22849590
TI  - Elongation of planar boron clusters by hydrogenation: boron analogues of
      polyenes.
AB  - Dihydrogenated boron clusters, H(2)B(n)(-) (n = 7-12), were produced and
      characterized using photoelectron spectroscopy and computational chemistry to
      have ladderlike structures terminated by a hydrogen atom on each end. The two
      rows of boron atoms in the dihydrides are bonded by delocalized three-, four-, or
      five-center sigma and pi bonds. The pi bonding patterns in these boron
      nanoladders bear similarities to those in conjugated alkenes: H(2)B(7)(-),
      H(2)B(8), and H(2)B(9)(-), each with two pi bonds, are similar to butadiene,
      while H(2)B(10)(2-), H(2)B(11)(-), and H(2)B(12), each with three pi bonds, are
      analogous to 1,3,5-hexatriene. The boron cluster dihydrides can thus be
      considered as polyene analogues, or "polyboroenes". Long polyboroenes with
      conjugated pi bonds (analogous to polyacetylenes), which may form a new class of
      molecular wires, should exist.

PMID- 22849591
TI  - Querying phenotype-genotype relationships on patient datasets using semantic web
      technology: the example of Cerebrotendinous xanthomatosis.
AB  - BACKGROUND: Semantic Web technology can considerably catalyze translational
      genetics and genomics research in medicine, where the interchange of information
      between basic research and clinical levels becomes crucial. This exchange
      involves mapping abstract phenotype descriptions from research resources, such as
      knowledge databases and catalogs, to unstructured datasets produced through
      experimental methods and clinical practice. This is especially true for the
      construction of mutation databases. This paper presents a way of harmonizing
      abstract phenotype descriptions with patient data from clinical practice, and
      querying this dataset about relationships between phenotypes and genetic
      variants, at different levels of abstraction. METHODS: Due to the current
      availability of ontological and terminological resources that have already
      reached some consensus in biomedicine, a reuse-based ontology engineering
      approach was followed. The proposed approach uses the Ontology Web Language (OWL)
      to represent the phenotype ontology and the patient model, the Semantic Web Rule
      Language (SWRL) to bridge the gap between phenotype descriptions and clinical
      data, and the Semantic Query Web Rule Language (SQWRL) to query relevant
      phenotype-genotype bidirectional relationships. The work tests the use of
      semantic web technology in the biomedical research domain named cerebrotendinous
      xanthomatosis (CTX), using a real dataset and ontologies. RESULTS: A framework to
      query relevant phenotype-genotype bidirectional relationships is provided.
      Phenotype descriptions and patient data were harmonized by defining 28 Horn-like
      rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were
      designed following the initial list of competency questions. As the approach is
      based on OWL, the semantic of the framework adapts the standard logical model of
      an open world assumption. CONCLUSIONS: This work demonstrates how semantic web
      technologies can be used to support flexible representation and computational
      inference mechanisms required to query patient datasets at different levels of
      abstraction. The open world assumption is especially good for describing only
      partially known phenotype-genotype relationships, in a way that is easily
      extensible. In future, this type of approach could offer researchers a valuable
      resource to infer new data from patient data for statistical analysis in
      translational research. In conclusion, phenotype description formalization and
      mapping to clinical data are two key elements for interchanging knowledge between
      basic and clinical research.

PMID- 22849592
TI  - Classification of congenital midline upper lip sinuses: a case report and review
      of the literature.
AB  - BACKGROUND: We recently encountered a case of a midline upper lip sinus, one of
      the rarest congenital lip sinuses. Several embryological hypotheses have been
      proposed regarding the etiology of this rare disease, but it remains obscure.
      METHODS: We reviewed all cases of upper lip sinus reported in the English
      language through 2011, and classified them into three types according to
      accompanying anomalies and the site of the fistula. RESULTS: Twenty-eight studies
      involving 31 cases were reviewed and classified. A type I sinus was a midline
      sinus without accompanying anomalies. There were 13 such cases, with a female
      predilection. Type II sinuses were midline sinuses with accompanying anomalies,
      and there were nine such cases. Type III sinuses were lateral sinuses with or
      without accompanying anomalies; there were nine cases. CONCLUSIONS: Our
      classification scheme is not only convenient for clinical application, but also
      reflects the embryological process responsible for congenital lip sinuses.

PMID- 22849585
TI  - Phylogeography of speciation: allopatric divergence and secondary contact between
      outcrossing and selfing Clarkia.
AB  - The origins of hybrid zones between parapatric taxa have been of particular
      interest for understanding the evolution of reproductive isolation and the
      geographic context of species divergence. One challenge has been to distinguish
      between allopatric divergence (followed by secondary contact) versus primary
      intergradation (parapatric speciation) as alternative divergence histories. Here,
      we use complementary phylogeographic and population genetic analyses to
      investigate the recent divergence of two subspecies of Clarkia xantiana and the
      formation of a hybrid zone within the narrow region of sympatry. We tested
      alternative phylogeographic models of divergence using approximate Bayesian
      computation (ABC) and found strong support for a secondary contact model and
      little support for a model allowing for gene flow throughout the divergence
      process (i.e. primary intergradation). Two independent methods for inferring the
      ancestral geography of each subspecies, one based on probabilistic character
      state reconstructions and the other on palaeo-distribution modelling, also
      support a model of divergence in allopatry and range expansion leading to
      secondary contact. The membership of individuals to genetic clusters suggests
      geographic substructure within each taxon where allopatric and sympatric samples
      are primarily found in separate clusters. We also observed coincidence and
      concordance of genetic clines across three types of molecular markers, which
      suggests that there is a strong barrier to gene flow. Taken together, our results
      provide evidence for allopatric divergence followed by range expansion leading to
      secondary contact. The location of refugial populations and the directionality of
      range expansion are consistent with expectations based on climate change since
      the last glacial maximum. Our approach also illustrates the utility of combining
      phylogeographic hypothesis testing with species distribution modelling and fine
      scale population genetic analyses for inferring the geography of the divergence
      process.

PMID- 22849594
TI  - We need champions, passionate champions.

PMID- 22849595
TI  - Special report: new frontiers for palliative care: center for medicare and
      medicaid innovation.

PMID- 22849596
TI  - Redefining the specialist palliative approach: clinical trials, a first year
      experience.

PMID- 22849597
TI  - Terminal cancer patients' informed consent for palliative care admission and
      their quality of life.

PMID- 22849599
TI  - Topical capsaicin for neuropathic pain #255.

PMID- 22849598
TI  - Minor children of palliative patients: a systematic review of psychosocial family
      interventions.
AB  - Although the whole family is affected by a parent's palliative disease,
      palliative care research does not yet routinely consider patients' minor
      children. Children's and adolescents' psychosocial functioning may be impaired
      during prolonged parental disease with poor prognosis. Therefore, more and more
      health care providers are establishing clinical initiatives for families of
      palliative patients with minor children. However, the number of these family
      interventions, as well as their theoretical and empirical backgrounds and
      evidence base, has yet to be determined. The purpose of this study was to
      systematically review structured and published interventions for this target
      group, as well as empirical studies on these interventions. The evidence base and
      impact of interventions on families were considered. Literature published between
      1980 and present focusing on psychosocial family-, child- or parent-centered
      interventions during palliative care was retrieved from PsycINFO(r), Embase,
      MEDLINE(r), CINAHL(r), and PSYNDEX databases. Five interventions met the
      inclusion criteria. Programs focused on different populations, had diverse
      empirical and theoretical backgrounds and features, and were evaluated by studies
      of varying methodological quality. This systematic review illustrates the lack of
      well designed and elaborated intervention concepts and evaluation studies in this
      field, highlighting the necessity of conceptual and methodological rigor to
      inform clinical practice on a sustainable basis in the future.

PMID- 22849600
TI  - Fever near the end of life #256.

PMID- 22849601
TI  - It takes the time that it takes.

PMID- 22849606
TI  - Hypothalamic glycogen synthase kinase 3beta has a central role in the regulation
      of food intake and glucose metabolism.
AB  - GSK3beta (glycogen synthase kinase 3beta) is a ubiquitous kinase that plays a key
      role in multiple intracellular signalling pathways, and increased GSK3beta
      activity is implicated in disorders ranging from cancer to Alzheimer's disease.
      In the present study, we provide the first evidence of increased hypothalamic
      signalling via GSK3beta in leptin-deficient Lep(ob/ob) mice and show that
      intracerebroventricular injection of a GSK3beta inhibitor acutely improves
      glucose tolerance in these mice. The beneficial effect of the GSK3beta inhibitor
      was dependent on hypothalamic signalling via PI3K (phosphoinositide 3-kinase), a
      key intracellular mediator of both leptin and insulin action. Conversely, neuron
      specific overexpression of GSK3beta in the mediobasal hypothalamus exacerbated
      the hyperphagia, obesity and impairment of glucose tolerance induced by a high
      fat diet, while having little effect in controls fed standard chow. These results
      demonstrate that increased hypothalamic GSK3beta signalling contributes to
      deleterious effects of leptin deficiency and exacerbates high-fat diet-induced
      weight gain and glucose intolerance.

PMID- 22849608
TI  - Repressed and silent suffering: consequences of childhood sexual abuse for
      women's health and well-being.
AB  - Research results indicate that psychological trauma in childhood caused by child
      sexual abuse can have serious and widespread consequences for health and well
      being. The purpose of this study was to examine the consequences of childhood
      sexual abuse for women's health and well-being. The research methodology was
      phenomenology. Seven women with a history of childhood sexual abuse were
      interviewed twice with 1-6 months interval. For all the women, the abuse started
      when they were between 4 and 5. All of them were repeatedly violated and
      traumatized ever since then and were even still being victimized at the time of
      the interviews. The main result of the study is that time does not heal all
      wounds. All the women described great repressed and silent suffering in all
      aspects of life, and the abuse is still seriously affecting them and their loved
      ones. As children, they had learning problems, experienced bullying and had
      unexplained physical symptoms. In adulthood, they have been suffering multiple
      physical and psychological symptoms: five of them have fibromyalgia; all of them
      have been suffering chronic and widespread pain; they have all been dealing with
      depression and difficulty with close connections, and they all have trouble
      trusting others. Because they were kids, they have been using the health service
      to a great extent but without adequate help. It is important for health
      professionals to know the symptoms and consequences of childhood sexual abuse to
      be able to respond to adult survivors in a supportive and caring way. More
      effective therapeutic measures have to be developed to decrease their suffering.

PMID- 22849607
TI  - A 12-week after-school physical activity programme improves endothelial cell
      function in overweight and obese children: a randomised controlled study.
AB  - BACKGROUND: Endothelial dysfunction is associated with childhood obesity and is
      closely linked to the amount and function of endothelial progenitor cells.
      However, it remains unclear whether endothelial progenitor cells increase with
      after-school exercise in overweight and obese children. The purpose of this study
      was to investigate the effects of an after-school exercise programme on
      endothelial cell function in overweight and obese children. METHODS: A total of
      29 overweight/obese children (12.2 +/- 0.1 years) were randomly divided into
      control (i.e. no after-school exercise, n = 14) and after-school exercise (n =
      15) groups. The 12-week after-school exercise intervention consisted of 3 days of
      combined aerobic and resistance exercise per week. Each 80-minute exercise
      programme included 10 minutes of warm-up and 10 minutes of cool-down after
      school. CD34(+) (a cell surface marker on hematopoietic stem cells), CD133(+) (a
      cell surface marker on hematopoietic progenitor cells) and CD34(+)/CD133(+)
      (considered as endothelial progenitor cells) were measured at baseline and after
      12 weeks using flow cytometry. RESULTS: Increased percentages of CD34(+),
      CD133(+) and CD34(+)/CD133(+) cells were observed in the after-school exercise
      group (p = 0.018; p = 0.001; p = 0.002, respectively) compared with the control
      group. Carotid intima-media thickness decreased after 12 weeks in the after
      school exercise group (p = 0.020) compared with the control group. CONCLUSIONS:
      This study provides preliminary evidence that a combined after-school exercise
      programme may represent an effective intervention strategy for improving vascular
      repair and endothelial cell function, leading to improved cardiovascular health
      in overweight and obese children. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN19037201.

PMID- 22849609
TI  - Willingness to accept and pay for implantable tinnitus treatments: a survey.
AB  - OBJECTIVES: At present, there is no cure for tinnitus. Neurostimulation
      techniques have shown great promise, but it is uncertain whether they will gain
      acceptance because of their invasive nature. We have previously demonstrated that
      pairing acoustic stimuli with vagus nerve stimulation (VNS) also has potential as
      a viable tinnitus treatment approach. METHODS: We conducted a survey on tinnitus
      sufferers that emphasized questions related to a willingness to pay for the
      treatment of tinnitus, including VNS. Four hundred thirty-nine individuals
      responded to an Internet survey modeled after a recent study by Tyler. RESULTS:
      The average age was about 47 years. Ninety-four percent reported that they had
      health insurance. Almost 40% had spent between $500 and $10,000 on tinnitus
      therapies. Almost three-fourths said that they would be willing to have a device
      implanted if it reduced tinnitus annoyance by half. About 70% of those with very
      loud tinnitus would be willing to have a temporary implant, and about 60% would
      be willing to have a permanent implant even if the device suppressed their
      tinnitus by only half of its annoyance. Only 10% of patients with SOFT tinnitus
      would be willing to have a permanent implant if the therapy suppressed their
      tinnitus by only half of its annoyance. CONCLUSIONS: We conclude that implanted
      devices, such as a VNS, will be an acceptable form of tinnitus treatment for many
      who suffer from tinnitus. The results of this survey indicate that VNS tone
      pairing would be an acceptable therapeutic solution for individuals with moderate
      to severe tinnitus and should be developed for the market.

PMID- 22849610
TI  - Individuals at risk for Alzheimer's disease show differential patterns of ERP
      brain activation during odor identification.
AB  - BACKGROUND: Studies suggest that older adults at risk of developing Alzheimer's
      disease may show olfactory processing deficits before other signs of dementia
      appear. METHODS: We studied 60 healthy non-demented individuals, half of whom
      were positive for the genetic risk factor the Apolipoprotein E epsilon4 allele,
      in three different age groups. Event-related potentials to visual and olfactory
      identification tasks were recorded and analyzed for latency and amplitude
      differences, and plotted via topographical maps. RESULTS: Varying patterns of
      brain activation were observed over the post-stimulus epoch for epsilon4- versus
      epsilon4+ individuals on topographical maps. Individuals with the epsilon4 allele
      demonstrated different ERP peak latencies during identification of olfactory but
      not visual stimuli. High correct ApoE classification rates were obtained
      utilizing the olfactory ERP. CONCLUSIONS: Olfactory ERPs demonstrate functional
      decline in individuals at risk for Alzheimer's disease at much earlier ages than
      previously observed, suggesting the potential for pre-clinical detection of AD at
      very early stages.

PMID- 22849611
TI  - The perception of positive and negative facial expressions in unilateral brain
      damaged patients: A meta-analysis.
AB  - How the brain is lateralised for emotion processing remains a key question in
      contemporary neuropsychological research. The right hemisphere hypothesis asserts
      that the right hemisphere dominates emotion processing, whereas the valence
      hypothesis holds that positive emotion is processed in the left hemisphere and
      negative emotion is controlled by the right hemisphere. A meta-analysis was
      conducted to assess unilateral brain-damaged individuals' performance on tasks of
      facial emotion perception according to valence. A systematic search of the
      literature identified seven articles that met the conservative selection criteria
      and could be included in a meta-analysis. A total of 12 meta-analyses of facial
      expression perception were constructed assessing identification and labelling
      tasks according to valence and the side of brain damage. The results demonstrated
      that both left and right hemisphere damage leads to impairments in emotion
      perception (identification and labelling) irrespective of valence. Importantly,
      right hemisphere damage prompted more pronounced emotion perception impairment
      than left hemisphere damage, across valence, suggesting right hemisphere
      dominance for emotion perception. Furthermore, right hemisphere damage was
      associated with a larger tendency for impaired perception of negative than
      positive emotion across identification and labelling tasks. Overall the findings
      support Adolphs, Jansari, and Tranel (2001) model whereby the right hemisphere
      preferentially processes negative facial expressions and both hemispheres process
      positive facial expressions. 

PMID- 22849612
TI  - Free haemoglobin in 'old' transfused blood - baddy or bystander?
AB  - In the previous issue of Critical Care, Vermeulen Windsant and colleagues
      demonstrate that transfusion of packed red cells is associated with a transient
      increase in plasma free haemoglobin and scavenging of nitric oxide in vitro. They
      also demonstrate that older units of blood have more free haemoglobin in their
      supernatants. Whether the administration of older stored blood results in adverse
      clinical outcomes is a topical clinical question. The present study proposes a
      mechanism for transfusion-related harm but also has implications for patients who
      have other sources of free haemoglobin in their circulation. 

PMID- 22849613
TI  - N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing
      mucin production with a high cholesterol diet in mice.
AB  - BACKGROUND AND AIM: The increasing prevalence of cholesterol gallstone (CG)
      disease has become an economic burden to the healthcare system. Ursodeoxycholic
      acid (UDCA) is the only established medical agent used to dissolve gallstones. In
      investigating novel therapeutics for CG, we assessed the preventive effects of n
      3 polyunsaturated fatty acids (n-3PUFA) on the formation of CG induced by feeding
      a lithogenic diet (LD) containing high cholesterol levels to mice. METHODS: Mice
      were divided into the following six groups: (A) regular diet (RD); (B) RD+n
      3PUFA; (C) LD; (D) LD+n-3PUFA; (E) LD+UDCA; (F) LD+n-3PUFA+UDCA. After RD/LD
      feeding for 2 weeks, n-3PUFA or UDCA was administered orally and the diet
      maintained for 8 weeks. The levels of phospholipids and cholesterol in bile, CG
      formation, gallbladder wall thickness, MUC gene expression in gallbladder were
      analyzed. RESULTS: No stone or sludge was evident in the RD groups (Groups A, B).
      Mice in the n-3PUFA treatment (Groups D, F) showed significantly lower stone
      formation than the other LD groups (Groups C, E). The combination treatment of n
      3PUFA and UDCA suppressed stone formation more than mono-therapy with n-3PUFA or
      UDCA. Bile phospholipid levels were significantly elevated in the Group F.
      Hypertrophy of the gallbladder wall was evident in mice fed LD. MUC 2, 5AC, 5B
      and 6 mRNA expression levels were significantly elevated in the LD-fed group, and
      this was suppressed by n-3PUFA with or without UDCA. CONCLUSIONS: N-3PUFA
      attenuated gallstone formation in mouse, through increasing the levels of bile
      phospholipids and suppressing bile mucin formation.

PMID- 22849614
TI  - Increase in subcutaneous adipose tissue and fat free mass in women with
      polycystic ovary syndrome is related to impaired insulin sensitivity.
AB  - OBJECTIVES: The present study was performed to search whether subcutaneous and
      whole body adipose tissue increase and they relate to measures of insulin
      sensitivity in women with polycystic ovary syndrome (PCOS). MATERIALS AND
      METHODS: 52 women with PCOS and 53 healthy controls, all with similar age and
      body mass index participated in the study. A skinfold caliper device was used to
      measure biceps, triceps, subscapular and suprailiac skinfold thickness (SFT). Mid
      upper arm circumference (MUAC) was measured using a tape measure. Body fat
      distributions were determined by bioelectrical impedance analysis. Insulin
      resistance score was computed with the HOMA formula. Plasma adiponectin was
      measured by EIA. RESULTS: SFT in all defined areas, MUAC, total body and trunk
      fat free mass, and HOMA score were higher in women with PCOS compared with
      healthy women, while adiponectin level was significantly lower. SFT values
      correlated positively with HOMA score, and negatively with blood adiponectin
      level. Regression analysis indicated, SFT in triceps and supscapular areas, trunk
      fat mass, trunk fat ratio, fat free mass and trunk fat free mass values as the
      most powerful predictors of HOMA score. CONCLUSIONS: The present study showed
      that SFT in different body regions and fat-free tissue mass are increased in
      women with PCOS, with a significant relation to impaired insulin sensitivity.

PMID- 22849615
TI  - Synthesis and study of 2-(pyrrolesulfonylmethyl)-N-arylimines: a new class of
      inhibitors for human glutathione transferase A1-1.
AB  - Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We
      report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting
      from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed
      two locations in the enzyme H binding site: the catalytic primary one
      accommodating shorter and longer derivatives and the secondary one, where shorter
      derivatives can occupy. Derivative 9, displaying the highest inhibition and
      bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were
      studied kinetically. Derivative 9 binds (K(i(9)) = 71 +/- 4 MUM) at the primary
      site competitively vs CDNB. Derivative 4 binds (K(i(4)) = 135 +/- 27 MUM) at the
      primary and secondary sites, allowing the binding of a second molecule (4 or
      CDNB) leading to formation of unreactive and reactive complexes, respectively.
      The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1,
      whereas its derivative 9 may serve as a lead structure.

PMID- 22849616
TI  - Strategies for the generation, validation and application of in silico ADMET
      models in lead generation and optimization.
AB  - INTRODUCTION: The most desirable chemical starting point in drug discovery is a
      hit or lead with a good overall profile, and where there may be issues; a clear
      SAR strategy should be identifiable to minimize the issue. Filtering based on
      drug-likeness concepts are a first step, but more accurate theoretical methods
      are needed to i) estimate the biological profile of molecule in question and ii)
      based on the underlying structure-activity relationships used by the model,
      estimate whether it is likely that the molecule in question can be altered to
      remove these liabilities. AREAS COVERED: In this paper, the authors discuss the
      generation of ADMET models and their practical use in decision making. They
      discuss the issues surrounding data collation, experimental errors, the model
      assessment and validation steps, as well as the different types of descriptors
      and statistical models that can be used. This is followed by a discussion on how
      the model accuracy will dictate when and where it can be used in the drug
      discovery process. The authors also discuss how models can be developed to more
      effectively enable multiple parameter optimization. EXPERT OPINION: Models can be
      applied in lead generation and lead optimization steps to i) rank order a
      collection of hits, ii) prioritize the experimental assays needed for different
      hit series, iii) assess the likelihood of resolving a problem that might be
      present in a particular series in lead optimization and iv) screen a virtual
      library based on a hit or lead series to assess the impact of diverse structural
      changes on the predicted properties.

PMID- 22849617
TI  - Directional control-response compatibility of joystick steered shuttle cars.
AB  - Shuttle cars are an unusual class of vehicle operated in underground coal mines,
      sometimes in close proximity to pedestrians and steering errors may have very
      serious consequences. A directional control-response incompatibility has
      previously been described in shuttle cars which are controlled using a steering
      wheel oriented perpendicular to the direction of travel. Some other shuttle car
      operators are seated perpendicular to the direction of travel and steer the car
      via a seat mounted joystick. A virtual simulation was utilised to determine
      whether the steering arrangement in these vehicles maintains directional control
      response compatibility. Twenty-four participants were randomly assigned to either
      a condition corresponding to this design (consistent direction), or a condition
      in which the directional steering response was reversed while driving in-bye
      (visual field compatible). Significantly less accurate steering performance was
      exhibited by the consistent direction group during the in-bye trials only.
      Shuttle cars which provide the joystick steering mechanism described here require
      operators to accommodate alternating compatible and incompatible directional
      control-response relationships with each change of car direction. PRACTITIONER
      SUMMARY: A virtual simulation of an underground coal shuttle car demonstrates
      that the design incorporates a directional control-response incompatibility when
      driving the vehicle in one direction. This design increases the probability of
      operator error, with potential adverse safety and productivity consequences.

PMID- 22849618
TI  - Nanostructured polyaniline-decorated Pt/C@PANI core-shell catalyst with enhanced
      durability and activity.
AB  - We have designed and synthesized a polyaniline (PANI)-decorated Pt/C@PANI core
      shell catalyst that shows enhanced catalyst activity and durability compared with
      nondecorated Pt/C. The experimental results demonstrate that the activity for the
      oxygen reduction reaction strongly depends on the thickness of the PANI shell and
      that the greatest enhancement in catalytic properties occurs at a thickness of 5
      nm, followed by 2.5, 0, and 14 nm. Pt/C@PANI also demonstrates significantly
      improved stability compared with that of the unmodified Pt/C catalyst. The high
      activity and stability of the Pt/C@PANI catalyst is ascribed to its novel PANI
      decorated core-shell structure, which induces both electron delocalization
      between the Pt d orbitals and the PANI pi-conjugated ligand and electron transfer
      from Pt to PANI. The stable PANI shell also protects the carbon support from
      direct exposure to the corrosive environment.

PMID- 22849619
TI  - One-step cyclization: synthesis of N-heteroalkyl-N'-tosylpiperazines.
AB  - Piperazine derivatives are important intermediates in organic synthesis and
      useful building blocks in pharmaceutical and fine chemical industries. Currently
      available synthetic routes for these heterocyclic compounds have limited scope
      owing to the harsh reaction conditions, low yields, and multistep process.
      Herein, we reported a practical method for synthesis of alkyl-, alcohol-, amine-,
      and ester-extended tosylpiperazines under mild conditions with moderate to high
      yields. This protocol exhibits potential applicability in the synthesis of
      pharmaceuticals and natural products because of the operational simplicity and
      the conveniently available reactants. On the basis of the experimental and
      theoretical results, a plausible mechanism of aliphatic nucleophilic substitution
      (S(N)) in the cyclization has been postulated and evidence for the formation of a
      six-membered ring has also been confirmed by means of density functional theory
      (DFT) calculations.

PMID- 22849620
TI  - Effects of a healthy food supply intervention in a military setting: positive
      changes in cereal, fat and sugar containing foods.
AB  - BACKGROUND: In Finland, all men are liable to military service and a clear
      majority completes service. The increasing prevalence of obesity also among
      soldiers concerns conscripts' food choices. Conscripts are served nutritionally
      planned regular main meals but individual choices take place in free-time eating.
      This study assesses the effects in conscripts' eating habits in an intervention
      targeting the supply of healthy foods available in the military setting. METHODS:
      Participants were 604 18-21-year old male conscripts of whom 242 belonged to
      Control Group and 362 to Intervention Group. Participants of Control Group were
      historical controls performing military service one year before Intervention
      Group. The intervention targeted selection, placement, and attractiveness of
      healthy foods in garrison refectories and soldier's home cafeterias, the two main
      food providers in the military. Dietary intake data was collected by self
      administered questionnaire at three time points: before/beginning of military
      service (T0), 8 weeks (T1) and 6 months (T2) of military service. Outcome
      measures were food consumption frequencies and four dietary indexes (Cereal
      Index, Fruit and Vegetable Index, Fat Index and Sugar Index) developed to
      characterize the diet. Changes between study groups in outcome variables and in
      time were analysed by repeated-measures analysis of covariance. RESULTS:
      Significant (p < 0.05) intervention effects and time-intervention interactions
      mostly in favor of Intervention Group were found. In Intervention Group, Cereal
      Index was significantly higher at T2 and the overall level of porridges and
      cereals was higher during follow-up when comparing to Control Group. Also, the
      overall levels of Fat Index, potato chips, soft drinks and desserts as well as
      sweet pastries at T1 were significantly lower in Intervention Group. At the same
      time, Fruit and Vegetable Index and the level of fruit and berries were lower in
      Intervention Group during follow-up. CONCLUSIONS: In the military setting,
      healthier food choices can be promoted by intervening on the main food
      environments by improving the supply of healthy foods. However, impacting on
      conscripts' individual selection as fruit and vegetable consumption is more
      challenging.

PMID- 22849621
TI  - Utilization of evidence-based treatment in elderly patients with chronic heart
      failure: using Korean Health Insurance claims database.
AB  - BACKGROUND: Chronic heart failure accounts for a great deal of the morbidity and
      mortality in the aging population. Evidence-based treatments include angiotensin
      2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I),
      beta-blockers, and aldosterone antagonists. Underutilization of these treatments
      in heart failure patients were frequently reported, which could lead to increase
      morbidity and mortality. The aim of this study was to evaluate the utilization of
      evidence-based treatments and their related factors for elderly patients with
      chronic heart failure. METHODS: This is retrospective observational study using
      the Korean National Health Insurance claims database. We identified prescription
      of evidence based treatment to elderly patients who had been hospitalized for
      chronic heart failure between January 1, 2005, and June 30, 2006. RESULTS: Among
      the 28,922 elderly patients with chronic heart failure, beta-blockers were
      prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total
      population. Multivariable logistic regression analyses revealed that the
      prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31-4.72),
      specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12-1.54),
      residence in urban (prevalent ratio, 1.37, 95% CI, 1.23-1.52) and admission to
      tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85-2.31) were important
      factors associated with treatment underutilization. Patients not given evidence
      based treatment were more likely to experience dementia, reside in rural areas,
      and have less-specialized healthcare providers and were less likely to have
      coexisting cardiovascular diseases or concomitant medications than patients in
      the evidence-based treatment group. CONCLUSIONS: Healthcare system factors, such
      as hospital type, healthcare provider factors, such as specialty, and patient
      factors, such as comorbid cardiovascular disease, systemic disease with
      concomitant medications, together influence the underutilization of evidence
      based pharmacologic treatment for patients with heart failure.

PMID- 22849624
TI  - Should you have a speakers' table?

PMID- 22849622
TI  - kappa-Casein-based hierarchical suprastructures and their use for selective
      temporal and spatial control over neuronal differentiation.
AB  - Functions are diversified by producing hierarchical structures from a single raw
      material. Biologically compatible milk protein of kappa-casein has been employed
      to fabricate higher-order suprastructures. In the presence of dithiothreitol and
      heat treatment, kappa-casein transforms into amyloid fibrils with distinctive
      morphology attributable to mechanism-based fibrillar polymorphism. As the fibrils
      elongate to yield high aspect ratio during high-temperature incubation, the
      resulting fibrils laterally associate into the liquid crystalline state by
      forming a two-dimensional fibrillar array. Following a desalting process, the
      fibrillar arrays turn into a three-dimensional matrix of hydrogel that could be
      selectively disintegrated by subsequent salt treatment. The hydrogel was
      demonstrated to be a matrix capable of exhibiting controlled release of bioactive
      substances like retinoic acid, which led to temporal and spatial control over the
      differentiation of neuronal cells. Therefore, the hierarchical suprastructure
      formation derived from the single protein of kappa-casein producing one
      dimensional protein nanofibrils, a two-dimensional liquid crystalline state and a
      three-dimensional hydrogel could be widely appreciated in various areas of
      nanobiotechnology including drug delivery and tissue engineering.

PMID- 22849625
TI  - Celebrations.

PMID- 22849626
TI  - Transforming continuing education across the health professions.
AB  - Transforming continuing education (CE) in the health professions requires a focus
      on competence and performance improvement by all health care professionals to
      ensure the public's trust. Measures of competence include individual, team, and
      systems-based performance meeting the growing expectations for quality care by
      consumers and the government. CE professionals have a critical role in meeting
      these new expectations for health care professionals as they pursue their
      continued professional development. This competence-based framework demands new
      knowledge, skills, and abilities for the CE health professional, including
      standardization and formalization of this field as an emerging profession.

PMID- 22849627
TI  - NICU perspectives on palliative care.
AB  - Few health care professionals have received palliative care training to comfort
      dying infants and their families. One institution's development of a palliative
      care program in the neonatal intensive care unit setting is discussed in this
      column.

PMID- 22849628
TI  - Developing and using multiple-choice tests in clinical settings.
AB  - Tests can be used to assess attitudes, knowledge, and comprehension of principles
      in clinical scenarios across a range of content areas. Multiple-choice tests,
      when well prepared, can be an efficient means of achieving these aims. They can
      also be used to introduce a topic or to assess prior knowledge for an in-service
      education session or workshop.

PMID- 22849630
TI  - Silver(I) ethynide coordination networks and clusters assembled with tert
      butylphosphonic acid.
AB  - Variation of the reaction conditions with AgC=CR (R = Ph, C(6)H(4)OCH(3)-4,
      (t)Bu), (t)BuPO(3)H(2), and AgX (X = NO(3), BF(4)) as starting materials afforded
      four new silver(I) ethynide complexes incorporating the tert-butylphosphonate
      ligand, namely, 3AgC=CPh.Ag(2)(t)BuPO(3).Ag(t)BuPO(3)H.2AgNO(3) (1),
      2AgC=CC(6)H(4)OCH(3)-4.Ag(2)(t)BuPO(3).2AgNO(3) (2),
      [{Ag(5)(NO(3)@Ag(18))Ag(5)}((t)BuC=C)(16)((t)BuPO(3))(4)(H(2)O)(3)][{Ag(5)(NO(3)@
      g(18))Ag(5)} ((t)BuC=C)(16)((t)BuPO(3))(4)(H(2)O)(4)].3SiF(6).4.5H(2)O.3.5MeOH
      (3), and
      [{Ag(8)(Cl@Ag(14))}((t)BuC=C)(14)((t)BuPO(3))(2)F(2)(H(2)O)(2)]BF(4).3.5H(2)O
      (4). Single-crystal X-ray analysis revealed that complexes 1 and 2 display
      different layer-type coordination networks, while 3 and 4 contain high-nuclearity
      silver(I) composite clusters enclosing nitrate and chloride template ions,
      respectively, that are supported by (t)BuPO(3)(2-) ligands.

PMID- 22849631
TI  - Hull split and damaged almond volatiles attract male and female navel orangeworm
      moths.
AB  - A blend of volatiles derived from the emissions of almonds at hull split and
      mechanically damaged almonds was compared to almond meal, the current monitoring
      standard for the insect pest navel orangeworm (NOW). Field trapping studies were
      performed to determine the blend's ability to attract adult NOW. The blend
      comprised racemic 1-octen-3-ol, ethyl benzoate, methyl salicylate, acetophenone,
      and racemic (E)-conophthorin. Ethyl acetate was used as a solvent with a blend
      component concentration of 100 mg/mL. The blend attracted both sexes of NOW when
      tested in five 2-week intervals spanning the first three flights of NOW in
      commercial almond orchards in the southern Central Valley of California. The
      blend demonstrated consistently higher capture rates for female NOW throughout
      the evaluation period, but unlike almond meal it significantly attracted males.
      Reported is a survey of the major and minor volatiles emitted from almonds at
      hull split, the key period of vulnerability to NOW infestation. Also reported is
      the attractancy of a formulated test blend based on the host plant volatile
      emissions, electroantennographic screening experiments, and field trapping
      studies. The results of this test blend highlight progress toward a host-plant
      based attractant for NOW, a major insect pest of California tree nuts that
      presently lacks an adequate monitoring tool.

PMID- 22849632
TI  - The FIFA Women's World Cup in Germany 2011--a practical example for tailoring an
      event-specific enhanced infectious disease surveillance system.
AB  - BACKGROUND: Mass gatherings require a decision from public health authorities on
      how to monitor infectious diseases during the event. The appropriate level of
      enhanced surveillance depends on parameters like the scale of the event
      (duration, spatial distribution, season), participants' origin, amount of public
      attention, and baseline disease activity in the host country. For the FIFA Men's
      World Cup 2006, Germany implemented enhanced surveillance. As the scale of the
      FIFA Women's World Cup (June 26 - July 17, 2011) was estimated to be
      substantially smaller in size, visitors and duration, it was not feasible to
      simply adopt the previously implemented measures. Our aim was therefore to
      develop a strategy to tailor an event-specific enhanced surveillance for this
      smaller-scale mass gathering. METHODS: Based on the enhanced surveillance
      measures during the Men's Cup, we conducted a needs assessment with the district
      health authorities in the 9 host cities in March 2011. Specific measures with a
      majority consent were implemented. After the event, we surveyed the 9 district
      and their corresponding 7 state health authorities to evaluate the implemented
      measures. RESULTS: All 9 district health authorities participated in the pre
      event needs assessment. The majority of sites consented to moving from weekly to
      daily (Monday-Friday) notification reporting of routine infectious diseases,
      receiving regular feedback on those notification reports and summaries of
      national/international World Cup-relevant epidemiological incidents, e.g.
      outbreaks in countries of participating teams. In addition, we decided to
      implement twice-weekly reports of "unusual events" at district and state level.
      This enhanced system would commence on the first day and continue to one day
      following the tournament. No World Cup-related infectious disease outbreaks were
      reported during this time period. Eight of 9 district and 6 of 8 state health
      authorities participated in the final evaluation. The majority perceived the
      implemented measures as adequate. CONCLUSIONS: Our approach to tailor an event
      specific enhanced surveillance concept worked well. Involvement of the
      participating stakeholders early-on in the planning phase secured ownership of
      and guaranteed support for the chosen strategy. The enhanced surveillance for
      this event resulted as a low-level surveillance. However, we included mechanisms
      for rapid upscaling if the situation would require adaptations.

PMID- 22849633
TI  - Convergent syntheses of 3,6-dihydroxydec-4-enolides.
AB  - The total syntheses of the 3,6-dihydroxydecanolide from Cordyceps militaris and
      the novel C-3 epimer are reported using a diastereoselective Nozaki-Hiyama-Kishi
      reaction in the key cyclization to generate the 6R stereocenter.

PMID- 22849634
TI  - Postsurgical alveolar bone graft patients: elaboration and application of a data
      gathering instrument for nutrition and nursing.
AB  - OBJECTIVES: To relate nutritional status with food acceptance by patients
      undergoing alveolar bone grafting and to elaborate an interdisciplinary
      instrument for data collection, involving nutrition and nursing teams.
      DESIGN/INTERVENTION: A prospective, longitudinal, and comparative study with a
      quantitative approach was conducted in a tertiary institutional hospital. The
      nutritional anthropometric evaluation was performed one day before surgery (M1)
      and at hospital discharge (M2), by measuring body mass index (BMI), triceps
      skinfold thickness (TST), subscapular skinfold thickness (SST), and arm muscle
      circumference (AMC). The interdisciplinary instrument for data collection was
      used. PATIENTS: The sample comprised 150 patients, aged 10 to 20 years, of both
      genders, who agreed to participate in this study. RESULTS: Most of patients were
      well-nourished during the study. There was correlation between BMI and Sigma TST
      + SST at M1 and M2 (P < .0001) and between BMI and AMC (P < .0001). Concerning
      food acceptance, 145 patients had adequate intake and 5 did not. Comparisons
      between the groups of patients revealed decreases in values for BMI, Sigma TST +
      SST, and AMC from -0.37, 0.0, and 0.3, respectively, at M1 to -0.71, -3.0, and
      0.0, respectively, at M2. BMI and AMC showed similar decreases in both groups.
      CONCLUSIONS: The interdisciplinary instrument was useful and appropriate for
      associating nutritional status with food acceptance, adding value for teamwork.

PMID- 22849635
TI  - Conservative management of severe open bite and feeding difficulties in patient
      with noonan syndrome.
AB  - Noonan syndrome is a multiple malformation disorder with an autosomal dominant
      inheritance pattern. Congenital heart defects, short stature, thoracic
      deformities, short neck with webbing, hypertelorism, malocclusions, and feeding
      difficulties are some of the commonly observed clinical features. We report on a
      case of a patient with Noonan syndrome, severe open bite, associated feeding
      difficulties, and strong gag reflex, discussing conservative management with
      myofunctional therapy. Myofunctional therapy has demonstrated a successful
      outcome, reestablishing masticatory function and routine dental home care after
      an 18-month follow-up.

PMID- 22849636
TI  - Comparison of two-dimensional and three-dimensional images for phenotypic
      assessment of craniofacial microsomia.
AB  - Background and Purpose :  Three-dimensional surface imaging is used in many
      craniofacial centers. However, few data exist to indicate whether such systems
      justify their cost. Craniofacial microsomia is associated with wide phenotypic
      variability and can affect most facial features. The purpose of this study is to
      compare three-dimensional versus two-dimensional images for classification of
      facial features in individuals with craniofacial microsomia. Methods :  We
      obtained a series of two-dimensional and three-dimensional images of 50
      participants, aged 0-20 years, diagnosed with craniofacial microsomia, microtia,
      or Goldenhar syndrome. Three clinicians classified the craniofacial features on
      each image, and ratings were compared by calculating kappa statistics. We also
      evaluated image quality using a 5-point Likert scale. Results :  Reliability
      estimates were high for most features using both two-dimensional and three
      dimensional image data. Our three-dimensional protocol did not allow for scoring
      of facial animation, occlusal cant, or tongue anomalies. Image quality scores for
      the mandible and soft tissue assessment were higher for three-dimensional images.
      Raters preferred two-dimensional photographs for assessment of the ear, ear
      canal, and eyes. Conclusions :  Both three-dimensional and two-dimensional images
      provide useful data for objective characterization of the craniofacial features
      affected in craniofacial microsomia. A series of two-dimensional images has
      relative advantages for assessment of some specific features, such as the ear,
      though three-dimensional images may have advantages for quantitative analysis and
      qualitative assessment of deformities of the jaw and soft tissue. These results
      should apply to any assessment of these features with or without a craniofacial
      microsomia diagnosis.

PMID- 22849637
TI  - Correction of the bilateral question mark ear deformity using double-opposing z
      plasty and a chondrocutaneous flap.
AB  - OBJECTIVE: To describe an alternative technique for correcting a rare and complex
      ear deformity. INTRODUCTION: The question mark ear deformity has been described
      as a congenital cleft between the helix and the lobule in addition to a prominent
      ear. Here we describe a novel technique using double-opposing Z-plasty and a
      chondrocutaneous flap to correct the deformity without significant reduction in
      auricle height or creation of a donor-site defect. METHODS: An anterior/posterior
      double-opposing Z-plasty and a superiorly based chondrocutaneous flap were
      designed at the level of the cleft. Flaps were raised full thickness, and
      Mustarde and Furnas sutures were placed to reduce the prominence. The flaps were
      then transposed and reapproximated. Of note, all anterior and posterior skin
      flaps were used in the repair to minimize diminution of ear height. Pre- and
      postoperative measurements and photographs of the ears were taken. RESULTS:
      Postoperatively, all flaps were viable, and there was no evidence of skin
      necrosis. The total length of the left ear was reduced by only 3 mm (53 to 50
      mm), and the right ear was reduced by 1 mm (52 to 51 mm). The patient's pain was
      successfully managed as an outpatient, and there were no infectious
      complications. The resultant scars healed aesthetically and are minimally
      visible. The patient and her parents are satisfied with the results. CONCLUSION:
      Our technique addresses all components of the question mark ear deformity and
      does not create a visible donor-site deformity.

PMID- 22849638
TI  - Morphometric evaluation of craniofacial and alveolar arch structures in
      anencephalic human fetuses: a cadaveric study.
AB  - Objective : The aim of the present study was to compare the morphometrics of the
      craniofacial and alveolar arch structures of anencephalic fetuses with those of
      normal human fetuses without anencephaly or any other anomaly. Design : Original
      article. Methods : Standard lateral and posteroanterior cephalometric radiographs
      of 23 anencephalic and 33 normal human fetuses aged between 21 and 40 weeks of
      gestation were compared. These fetuses were divided into three periods based on
      gestational age, and vertical, sagittal, transverse, and angular measurements
      were taken in the cranial base and facial regions. Moreover, intraoral
      measurements from the maxillary and mandibular arches were also made to determine
      the width and depth. Results : N-S and S-Ba lengths and the N-S-Ba angle,
      measured on lateral cephalometric radiographs, were statistically smaller in
      anencephalic fetuses (p < .05). The S-N-ANS, S-N-Pg, and ANS-N-Pg angles and the
      Go-Me length were significantly greater in anencephalic fetuses (p < .05).
      Maxillary length, ramus length, and anterior facial heights were similar in both
      groups. On posteroanterior radiographs, all parameters except bigonial distance
      were found to be smaller in the anencephalic fetuses (p < .05). Maxillary
      alveolar width was small among anencephalic fetuses in all three periods;
      whereas, the mandibular alveolar width was narrow only in the third period.
      Conclusion : Cranial and facial structures were affected morphometrically to
      various degrees in anencephalic cases. The most significant alterations in
      anencephalic cases were related to measurements in the transverse direction. This
      indicated that cephalic tissue influenced not only the cranial base but also all
      facial structures. 

PMID- 22849639
TI  - Anthropometric analysis of the maxillary bone and the alar base in unilateral
      cleft lip with secondary nasal deformity: classification of a piriform margin
      bony depression.
AB  - OBJECTIVES: This study was conducted to measure the soft tissue of the alar base
      and the piriform aperture area of the maxillary bone of unilateral cleft lips
      with secondary nasal deformities when secondary operation are necessary to
      classify the alar base depression and to provide a clinical reference for the
      second surgery. METHODS: Twenty-six patients with unilateral cleft lip with
      secondary nasal deformity were treated at the Department of Oral and
      Maxillofacial Surgery, School of Stomatology, China Medial University. Nose data
      were attained preoperatively and postoperatively. Correlations were made between
      the soft tissue and the bony depression and patient satisfaction with the nasi
      basis. Classifications were then made based on these data. RESULTS: When the
      distance discrepancy of the bilateral piriform aperture depression was less than
      4.5 mm, we obtained a fine appearance for the nose by repairing only the soft
      tissues. When it was more than 5 mm, we had to combine repair of the soft tissue
      with a bone graft or the restitution of the alveolar cleft. When the distance was
      between 4.5 mm and 5 mm, the surgeon considered both the wishes of the patient
      and the clinic's standard procedure. CONCLUSIONS: For patients with cleft lips
      and palates, the bony depression was not the only factor that resulted in
      postoperative alar depression. Anthropometry of the nose prior to surgery was
      important for choosing the methods that would yield satisfactory results.

PMID- 22849640
TI  - Dental arch relationships in Turkish patients with complete unilateral cleft lip
      and palate born between 1976 and 1990: a comparison with eurocleft.
AB  - OBJECTIVE: To compare the dental arch relationships of Turkish patients with
      complete unilateral cleft lip and palate (UCLP) with the results reported for
      participants in the Eurocleft study. PATIENTS: Study models of 109 patients with
      complete UCLP from five university clinics in Turkey were evaluated (clinic A =
      25 patients, clinic B = 23 patients, clinic C = 20 patients, clinic D = 21
      patients, and clinic E = 20 patients). The mean age of the patient cohort was
      nine years old (range = 8-11 years old), and the cohort was born between 1976 and
      1990. METHODS: The examiners rated the three-dimensional (3D) models using the
      GOSLON Yardstick. The scores were compared with those from the Eurocleft centers:
      E1(B), E2(E), E3(A), E4(F), E5(C), and E6(D). Intra- and interexaminer agreements
      were evaluated using weighted kappa statistics. RESULTS: The mean GOSLON scores
      for the Turkish clinics were as follows: clinic A = 3.16, clinic B = 3.13, clinic
      C = 3.25, clinic D = 3.67, and clinic E = 3.70. Scores for three of the Turkish
      clinics (A, B, and C) were significantly worse than the scores for the three best
      Eurocleft centers, E1(B), E2(E), and E3(A) (P < .001, P < .001, and P < .05,
      respectively). Scores for two of the Turkish clinics (D and E) were similar to
      those for Eurocleft center E6(D) but worse than the scores for the other
      Eurocleft centers (P < .01, P < .001, respectively). CONCLUSIONS: This was the
      first study in which three-dimensional models were used to derive scores to
      compare with those of the Eurocleft centers. According to the results of analysis
      of 109 3D models, 50.4 % of the patients in Turkey were classified as GOSLON
      score 4 and 5. This may have been attributable to poor surgical procedures, low
      volume surgeons, and the decentralized treatment approach in Turkey between 1985
      and 2000. Further research is needed to assess the situation in Turkey in more
      recent years.

PMID- 22849641
TI  - Parents' Perspectives of Cleft Lip and/or Palate Services: A Qualitative
      Interview.
AB  - The study aimed to explore in depth the perspectives of parents about their
      child's cleft services. Purposive and theoretical sampling produced a diverse
      sample of mothers and fathers with children aged 20 weeks to 21 years. Parents
      were recruited from a specialist cleft center in the U.K. Qualitative, in-depth,
      face-to-face interviews were carried out with 35 parents. Interviews were audio
      recorded, transcribed, and analyzed using grounded theory to identify salient
      data categories. Findings revealed that parents' positive views about services
      rested on their perceptions of cleft-care practitioners as competent and
      trustworthy, possessing highly developed communication skills and the ability to
      provide continuity of care to families. At the same time, some mothers and
      fathers identified unmet support needs relating to information delivery and
      content as well as the coordination of services across the treatment course. More
      individualized information about treatment was desired; in particular, some
      parents had incomplete information about their child's surgical procedures,
      associated risks, and postsurgical recovery. Parents wanted better coordination
      of services with regard to communication about surgical cancellations, a child's
      transition to adult services, and having a key professional to link with
      throughout their child's treatment course. Routine assessments to gauge parents'
      needs could be built into cleft-care pathways so that more individualized
      information and support might be delivered to families in more consistent ways
      over long-term treatment.

PMID- 22849643
TI  - In vitro reconstitution of RNA primer removal in Archaea reveals the existence of
      two pathways.
AB  - Using model DNA substrates and purified recombinant proteins from Pyrococcus
      abyssi, I have reconstituted the enzymatic reactions involved in RNA primer
      elimination in vitro. In my dual-labelled system, polymerase D performed
      efficient strand displacement DNA synthesis, generating 5'-RNA flaps which were
      subsequently released by Fen1, before ligation by Lig1. In this pathway, the
      initial cleavage event by RNase HII facilitated RNA primer removal of Okazaki
      fragments. In addition, I have shown that polymerase B was able to displace
      downstream DNA strands with a single ribonucleotide at the 5'-end, a product
      resulting from a single cut in the RNA initiator by RNase HII. After RNA
      elimination, the combined activities of strand displacement DNA synthesis by
      polymerase B and flap cleavage by Fen1 provided a nicked substrate for ligation
      by Lig1. The unique specificities of Okazaki fragment maturation enzymes and
      replicative DNA polymerases strongly support the existence of two pathways in the
      resolution of RNA fragments.

PMID- 22849642
TI  - Characteristics of U.S. emergency departments that offer routine human
      immunodeficiency virus screening.
AB  - OBJECTIVES: The association between emergency department (ED) characteristics, ED
      director's perceptions of preventive services, and the availability of human
      immunodeficiency virus (HIV) screening are unknown. The authors hypothesized
      that, after adjusting for ED operational and demographic characteristics,
      teaching hospital status would be associated with increased availability, and ED
      crowding and ED director agreement with barriers to screening would be associated
      with decreased availability. METHODS: This was a secondary, cross-sectional
      analysis on previously collected data from 2008 to 2009 regarding availability of
      ED preventive services. Data were obtained from a random sample of 277 EDs in
      which ED directors provided information on ED characteristics and availability of
      HIV screening and rated five barriers to providing preventive services. The
      association between the availability of HIV screening and teaching hospital and
      crowding status, ED volume, urban-rural location, ownership, geographic region,
      patient demographics, state HIV testing consent laws, and ED director opinions on
      barriers to providing preventive services were determined in univariate analyses
      and a multivariate logistic regression model. RESULTS: Nineteen percent of the
      sampled EDs offer HIV screening. Teaching hospitals offer HIV screening more
      frequently than nonteaching hospitals (38% vs. 18%; p = 0.03), but after
      adjusting for other characteristics in a multivariate model, this association was
      not significant (relative risk ratio [RR] = 2.07, 95% confidence interval [CI] =
      0.91 to 3.59). ED crowding also was not significantly associated with screening
      availability (RR = 0.66, 95% CI = 0.34 to 1.21). However, public ownership (RR =
      2.13, 95% CI = 1.28 to 3.14), 24-hour social work (RR = 1.87, 95% CI = 1.02 to
      2.99), uninsured population >=35% (RR = 2.48, 95% CI = 1.39 to 3.69), increased
      local nonwhite minority population percentage (RR = 1.14 per 10%, 95% CI = 1.02
      to 1.26), and state laws allowing opt-out consent for testing (RR = 1.76, 95% CI
      = 1.01 to 2.74) were associated with increased availability of screening in
      multivariable analysis. EDs whose directors were concerned about added costs were
      associated with decreased availability of screening (RR = 0.45, 95% CI = 0.23 to
      0.85). CONCLUSIONS: After adjusting for other ED operational and demographic
      characteristics, ED crowding and teaching hospital affiliation were not
      independently associated with the availability of HIV screening. EDs whose
      directors were concerned about the cost of preventive services were less likely
      to provide routine HIV screening. Addressing ED director's concerns about the
      added costs of ED preventive services, increasing social work availability, and
      implementing testing laws consistent with Centers for Disease Control and
      Prevention (CDC) recommendations may facilitate increased adoption of ED HIV
      screening.

PMID- 22849644
TI  - An ambiguous relationship--a qualitative meta-synthesis of hospitalized somatic
      patients' experience of interaction with fellow patients.
AB  - AIM: The aim of this study was to provide a clear view of the existing knowledge
      regarding patients' significance to fellow patients during hospitalization.
      METHOD: Sandelowski and Barroso's approach to qualitative meta-synthesis was
      selected and systematically used for collecting and assessing findings from
      qualitative studies. Data consisted of seven qualitative studies published as one
      book, four scientific articles and two doctoral theses from Scotland, UK, Norway
      and Denmark. The analysis and synthesis were conducted with inspiration from both
      Sandelowski and Barroso and Ian Dey's approach to qualitative data analysis.
      RESULTS: The qualitative meta-synthesis resulted in the heading An Ambiguous
      Relationship under which three core categories illustrate the hospitalized
      patients' different interaction roles. The core categories were as follows: (i)
      the fellow patient experienced as an enforced companion, (ii) the fellow patient
      experienced as an expert on illness and hospital life and (iii) the fellow
      patient experienced as a care provider. Each core category was elaborated through
      several subcategories. Social interaction among hospitalized patients embedded
      elements of both enforced and volunteered participation. Typically, the social
      interaction was experienced as giving and was referred to in positive terms but
      recurrently, the opposite was experienced too. The ambiguity of the relationship
      clearly emerged in all of the synthesized themes presented in this article.
      IMPLICATIONS FOR PRACTICE: Hospitalized patients experienced interaction with
      fellow patients to be of great significance. We suggest that knowledge of
      patients' interaction is to be included in the nursing education and that nurses
      reflect on how this knowledge may be implemented as a part of caring in nursing.

PMID- 22849645
TI  - Synthesis of novel 2'-spirocyclopropyl-5'- deoxyphosphonic acid furanosyl
      nucleoside analogues as potent antiviral agents.
AB  - Novel 5'-deoxyfuranosyl purine phosphonic acid analogues with 2 '-electropositive
      moiety, such as spirocyclopropanoid, were designed and synthesized from
      commercially available diethyl malonate. Condensation reaction successfully
      proceeded from a glycosyl donor 15 at low reaction temperature in Vorbruggen
      conditions to give desired phosphonate analogues 16b and 23b. The synthesized
      nucleotide analogues 19, 22, 26, and 29 were subjected to antiviral screening
      against HIV-1. Adenine phosphonic acid analogue 22 shows significant anti-HIV
      activity (EC(50) = 7.9 MUM).

PMID- 22849646
TI  - Stereocontrolled facile synthesis and biological evaluation of (3'S) and (3'R)-3'
      amino (and Azido)-3'-deoxy pyranonucleosides.
AB  - This article describes the synthesis of (3 'S) and (3 'R)-3 '-amino-3 '-deoxy
      pyranonucleosides and their precursors (3 'S) and (3 'R)-3 '-azido-3 '-deoxy
      pyranonucleosides. Azidation of 1,2:5,6-di-O-isopropylidene-3-O-toluenesulfonyl
      alpha-D-allofuranose followed by hydrolysis and subsequent acetylation afforded 3
      azido-3-deoxy-1,2,4,6-tetra-O-acetyl-D-glucopyranose, which upon coupling with
      the proper silylated bases, deacetylation, and catalytic hydrogenation, obtained
      the target 3 '-amino-3 '-deoxy-beta-D-glucopyranonucleosides. The desired 1-(3 '
      amino-3 '-deoxy-beta-D-allopyranosyl)5-fluorouracil was readily prepared from the
      suitable imidazylate sugar after azidation followed by a protection/deprotection
      sequence and reduction of the unprotected azido precursor. No antiviral activity
      was observed for the novel nucleosides. Moderate cytostatic activity was recorded
      for the 5-fluorouracil derivatives.

PMID- 22849647
TI  - A nucleotide dimer synthesis without protecting groups using montmorillonite as
      catalyst.
AB  - A synthesis has been developed providing nucleotide dimers comprising natural or
      unnatural nucleoside residues. A ribonucleoside 5'-phosphorimidazolide is added
      to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of
      protecting groups. Approximately 30% of the imidazolide is converted into each 2'
      5' dimer and 3'-5' dimer with the rest hydrolyzed to the 5'-monophosphate.
      Experiments with many combinations have suggested the limits to which this method
      may be applied, including heterochiral and chimeric syntheses. This greener
      chemistry has enabled the synthesis of dimers from activated nucleotides
      themselves, activated nucleotides with nucleosides, and activated nucleotides
      with nucleotide 5'-monophosphates.    [Supplemental materials are available for
      this article. Go to the publisher's online edition of Nucleosides, Nucleotides &
      Nucleic Acids to view the free supplemental files.].

PMID- 22849648
TI  - An efficient synthesis of pyrimidine specific 2'-deoxynucleoside-5'
      tetraphosphates.
AB  - An efficient chemical synthesis of pyrimidine specific 2'-deoxynucleoside-5'
      tetraphosphates, such as 2'-deoxycytidine-5'-tetraphosphate (dC4P) and thymidine
      5'-tetraphosphate (T4P) is described. The present three-step synthetic strategy
      involves monophosphorylation of 2'-deoxynucleoside using phosphorous oxychloride,
      conversion of 5'-monophosphate into the corresponding imidazolide salt, followed
      by reaction with tris[tributylammonium] triphosphate leading to the 2'
      deoxynucleoside-5'-tetraphosphate in good yields.

PMID- 22849649
TI  - Effective diagnosis of Alzheimer's disease by means of large margin-based
      methodology.
AB  - BACKGROUND: Functional brain images such as Single-Photon Emission Computed
      Tomography (SPECT) and Positron Emission Tomography (PET) have been widely used
      to guide the clinicians in the Alzheimer's Disease (AD) diagnosis. However, the
      subjectivity involved in their evaluation has favoured the development of
      Computer Aided Diagnosis (CAD) Systems. METHODS: It is proposed a novel
      combination of feature extraction techniques to improve the diagnosis of AD.
      Firstly, Regions of Interest (ROIs) are selected by means of a t-test carried out
      on 3D Normalised Mean Square Error (NMSE) features restricted to be located
      within a predefined brain activation mask. In order to address the small sample
      size problem, the dimension of the feature space was further reduced by: Large
      Margin Nearest Neighbours using a rectangular matrix (LMNN-RECT), Principal
      Component Analysis (PCA) or Partial Least Squares (PLS) (the two latter also
      analysed with a LMNN transformation). Regarding the classifiers, kernel Support
      Vector Machines (SVMs) and LMNN using Euclidean, Mahalanobis and Energy-based
      metrics were compared. RESULTS: Several experiments were conducted in order to
      evaluate the proposed LMNN-based feature extraction algorithms and its benefits
      as: i) linear transformation of the PLS or PCA reduced data, ii) feature
      reduction technique, and iii) classifier (with Euclidean, Mahalanobis or Energy
      based methodology). The system was evaluated by means of k-fold cross-validation
      yielding accuracy, sensitivity and specificity values of 92.78%, 91.07% and
      95.12% (for SPECT) and 90.67%, 88% and 93.33% (for PET), respectively, when a
      NMSE-PLS-LMNN feature extraction method was used in combination with a SVM
      classifier, thus outperforming recently reported baseline methods. CONCLUSIONS:
      All the proposed methods turned out to be a valid solution for the presented
      problem. One of the advances is the robustness of the LMNN algorithm that not
      only provides higher separation rate between the classes but it also makes (in
      combination with NMSE and PLS) this rate variation more stable. In addition,
      their generalization ability is another advance since several experiments were
      performed on two image modalities (SPECT and PET).

PMID- 22849650
TI  - Colonization pressure: a critical parameter in the epidemiology of antibiotic
      resistant bacteria.
AB  - The recognition of colonization pressure as an important risk factor for
      acquisition of antibiotic-resistant bacteria in the ICU, including Acinetobacter
      species, has major consequences for our understanding of risk factor analyses.
      Moreover, the importance of colonization pressure underpins the role of cross
      transmission in the dynamics of antibiotic-resistant bacteria in the ICU, which
      has major consequences for the evaluation of the effectiveness of infection
      control measures. 

PMID- 22849651
TI  - CRISPR transcript processing: a mechanism for generating a large number of small
      interfering RNAs.
AB  - BACKGROUND: CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic
      Repeats/CRISPR associated sequences) is a recently discovered prokaryotic defense
      system against foreign DNA, including viruses and plasmids. CRISPR cassette is
      transcribed as a continuous transcript (pre-crRNA), which is processed by Cas
      proteins into small RNA molecules (crRNAs) that are responsible for defense
      against invading viruses. Experiments in E. coli report that overexpression of
      cas genes generates a large number of crRNAs, from only few pre-crRNAs. RESULTS:
      We here develop a minimal model of CRISPR processing, which we parameterize based
      on available experimental data. From the model, we show that the system can
      generate a large amount of crRNAs, based on only a small decrease in the amount
      of pre-crRNAs. The relationship between the decrease of pre-crRNAs and the
      increase of crRNAs corresponds to strong linear amplification. Interestingly,
      this strong amplification crucially depends on fast non-specific degradation of
      pre-crRNA by an unidentified nuclease. We show that overexpression of cas genes
      above a certain level does not result in further increase of crRNA, but that this
      saturation can be relieved if the rate of CRISPR transcription is increased. We
      furthermore show that a small increase of CRISPR transcription rate can
      substantially decrease the extent of cas gene activation necessary to achieve a
      desired amount of crRNA. CONCLUSIONS: The simple mathematical model developed
      here is able to explain existing experimental observations on CRISPR transcript
      processing in Escherichia coli. The model shows that a competition between
      specific pre-crRNA processing and non-specific degradation determines the steady
      state levels of crRNA and is responsible for strong linear amplification of
      crRNAs when cas genes are overexpressed. The model further shows how
      disappearance of only a few pre-crRNA molecules normally present in the cell can
      lead to a large (two orders of magnitude) increase of crRNAs upon cas
      overexpression. A crucial ingredient of this large increase is fast non-specific
      degradation by an unspecified nuclease, which suggests that a yet unidentified
      nuclease(s) is a major control element of CRISPR response. Transcriptional
      regulation may be another important control mechanism, as it can either increase
      the amount of generated pre-crRNA, or alter the level of cas gene activity.

PMID- 22849652
TI  - Is startle a lateralised response in early infancy?
AB  - The aim of the study was to explore whether the acoustic startle response shows
      signs of early lateralisation. Using non-invasive startle measurements (Automated
      Infant Motor Movement Startle Seat and Facial Action Coding System), an analysis
      of response latencies and intensities on the right and left body sides was
      performed, investigating the presence of asymmetries on the whole-body startle
      and on the facial component of the startle motor pattern in a group of 5-month
      old infants. The findings suggest that the infant whole-body startle is a
      lateralised response, characterised by a right bias latency. This lateralisation
      could reflect an underlying lateralised organisation of the infant startle neural
      circuitry. On the other hand, the analysis of the facial component of the startle
      motor pattern did not reveal any significant asymmetry. The discrepancy found in
      the whole-body response and in the startle facial component will be discussed,
      reflecting on the limits of the adopted methodologies. The use of a high-speed
      camcorder might allow future research to analyse more in depth the startle fast
      face responses. 

PMID- 22849653
TI  - Rhodium(III)- and ruthenium(II)-catalyzed olefination of isoquinolones.
AB  - NH and N-protected isoquinolones undergo Rh(III)-catalyzed oxidative olefination
      at the 8-position. Complementary redox-neutral olefination of such isoquinolones
      using internal alkynes was achieved under ruthenium catalysis.

PMID- 22849654
TI  - High prevalence of pulmonary arterial hypertension in a cohort of asymptomatic
      HIV-infected patients.
AB  - HIV infection is considered a risk factor for the development of pulmonary
      arterial hypertension (PAH) and the estimated prevalence of PAH in developed
      countries is 0.5%. The aim of this study was to determine the prevalence of PAH
      in a cohort of HIV-infected patients and the related factors. We undertook an
      observational study of a consecutive cohort of asymptomatic HIV-infected
      patients. Data were recorded about factors of cardiovascular interest and factors
      related to HIV infection. All the patients underwent a transthoracic
      echocardiogram (Vivid S6, GE Healthcare). PAH was considered to be a pulmonary
      arterial systolic pressure (PASP) >40 mm Hg. The study included 194 patients
      (85.2% men) with a mean age of 47.0 years, 94% of whom were on antiretroviral
      therapy (ART). The mean CD4 lymphocyte count was 495/mm(3). The mean duration of
      HIV infection was 131.5 months, and 28.4% had experienced an AIDS event. PAH was
      present in five patients (2.6%) and 14 were in the gray zone (PASP of 36-40 mm
      Hg). These five patients were men, the route of transmission was homosexual, and
      they were all on ART. They were also older than the patients without PAH (57.7
      vs. 46.4 years, p=0.02) and had been on ART for longer (180.0 vs. 92.5 months;
      p=0.01). No association was found with any of the other parameters. The
      prevalence of PAH in this cohort of patients was greater than in other published
      series. The only associations found were with older age and longer ART time.

PMID- 22849655
TI  - beta-Carotene assay revisited. application to characterize and quantify
      antioxidant and prooxidant activities in a microplate.
AB  - The beta-carotene bleaching assay, a common method for evaluating antioxidant
      activity, has been widely criticized due to its low reproducibility, problematic
      quantification, complex reagent preparation, and interference of different
      factors (temperature, pH, solvents, and metals). In this work we have examined
      the effects of these factors and developed a highly reproducible procedure for
      microplate assay, evaluated the critical points of the method, and proposed a
      kinetic model for quantifying both antioxidant and prooxidant activities. The
      application of these tools produced very consistent results, which provide robust
      and meaningful criteria to compare in detail the characteristics of several well
      known commercial antioxidants, as well as several predictable prooxidants, and
      can be easily applied to natural extracts, food samples, and many other type of
      compounds. As an example, we have tested a set of commercial antioxidants and
      some typical lipophilic prooxidants. The activity of the tested antioxidants
      decreased in the following order: ethoxyquin ? alpha-tocopherol >
      butylhydroxyanisole > butylhydroxytoluene ? propyl gallate. On the other hand,
      hemoglobin and Fe(2+), Fe(3+), Co(2+), and Cu(2+) showed a strong prooxidant
      effect, and the activity was null in Cd(2+), Ni(2+), and Sr(2+), slightly
      antioxidant in Mg(2+), and strongly antioxidant in Zn(2+) and Mn(2+).

PMID- 22849656
TI  - NT, NPY and PGP 9.5 presence in myomeytrium and in fibroid  pseudocapsule and
      their possible impact on muscular physiology.
AB  - The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid,
      containing neuropeptides, probably involved in uterine scar healing. We studied
      neurotensin (NT), neuropeptide tyrosine (NPY), and protein gene product 9.5 (PGP
      9.5) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine
      fibroids on 67 no pregnant women by intracapsular myomectomy sparing the
      neurovascular bundle, sampling full thickness specimens of the pseudocapsule of
      uterine fibroids (PUF) and normal myometrium (NM) obtained from the fundus uteri
      (FU) and the uterine body (UB). The samples were sent for histological and
      immunofluorescent analyses and compared by morphometrical quantification. The
      Conventional Unit (C.U.) difference of NT, NPY, and PGP 9.5 nerve fibres was
      statistically analyzed. Our results showed that NT, NPY, and PGP 9.5 neurofibers
      are almost equally present in PUF as in NM of a no pregnant uterus. As all of
      these neuropeptides are present in the uterine muscle and can affect muscle
      contractility, uterine peristalsis and muscular healing. A myomectomy respecting
      the pseudocapsule neurofibers should facilitate smooth muscle scarring and
      promote restoration of normal uterine peristalsis with a possible positive
      influence on fertility.

PMID- 22849657
TI  - Diastolic dysfunction, prolonged QTc interval and pericardial effusion as
      predictors of mortality in acute pancreatitis.
AB  - BACKGROUND AND AIM: The cardiac changes in acute pancreatitis have been earlier
      studied but the data on their prognostic significance is limited. This study was
      done to determine electrocardiographic (ECG) and echocardiographic changes in
      acute pancreatitis and determine their prognostic significance. METHODS: Fifty
      two consecutive patients (mean age 36.5 +/- 11 years (44 males)) with acute
      pancreatitis and without prior cardiovascular comorbidites were prospectively
      enrolled and subjected to clinical, laboratory and radiological investigation.
      ECG and echocardiography was done at admission and during follow up. RESULTS:
      Seventeen patients (32.7%) had mild pancreatitis and 35 (67.3%) patients had
      severe pancreatitis. Sinus tachycardia was the most common ECG abnormality. QTc
      prolongation was seen in 30/52 (57.7%) patients. On echocardiography, no patient
      had systolic dysfunction but 31/52 (59.6%) patients had diastolic dysfunction.
      All 22 patients with QTc interval < 440 ms survived compared with 8/30 patients
      with QTc interval >= 440 ms who died (P = 0.01). All eight patients who died had
      evidence of diastolic dysfunction (100%). None of the patients without diastolic
      dysfunction succumbed to illness (P = 0.02). Pericardial effusion was present in
      6/52 (11.5%) patients. Of the eight patients who died, pericardial effusion was
      present in three (37.5%) patients and this frequency was significantly higher
      than that in patients who recovered (3/44 [6.8%]; P = 0.04). CONCLUSION:
      Electrocardiographic and echocardiographic changes are seen in more than 50% of
      patients with acute pancreatitis. Prolonged QTc interval, pericardial effusion
      and diastolic dysfunction are associated with higher mortality.

PMID- 22849658
TI  - The Global Lung Initiative 2012 reference values reflect contemporary
      Australasian spirometry.
AB  - We aimed to ascertain the fit of the European Respiratory Society Global Lung
      Initiative 2012 reference ranges to contemporary Australasian spirometric data. Z
      scores for spirometry from Caucasian subjects aged 4-80 years were calculated.
      The mean (SD) Z-scores were 0.23 (1.00) for forced expirtory volume in 1 s
      (FEV(1)), 0.23 (1.00) for forced vital capacity (FVC), -0.03 (0.87) for
      FEV(1)/FVC and 0.07 (0.95) for forced expiratory flows between 25% and 75% of
      FVC. These results support the use of the Global Lung Initiative 2012 reference
      ranges to interpret spirometry in Caucasian Australasians.

PMID- 22849660
TI  - Organometallic Ni pincer complexes for the electrocatalytic production of
      hydrogen.
AB  - Nonplatinum metals are needed to perform cost-effective water reduction
      electrocatalysis to enable technological implementation of a proposed hydrogen
      economy. We describe electrocatalytic proton reduction and H(2) production by two
      organometallic nickel complexes with tridentate pincer ligands. The kinetics of
      H(2) production from voltammetry is consistent with an overall third order rate
      law: the reaction is second order in acid and first order in catalyst. Hydrogen
      production with 90-95% Faradaic yields was confirmed by gas analysis, and UV-vis
      spectroscopy suggests that the ligand remains bound to the catalyst over the
      course of the reaction. A computational study provides mechanistic insights into
      the proposed catalytic cycle. Furthermore, two proposed intermediates in the
      proton reduction cycle were isolated in a representative system and show a
      catalytic response akin to the parent compound.

PMID- 22849659
TI  - Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports
      development of intestinal inflammation.
AB  - BACKGROUND: Mice lacking Foxp3+ regulatory T (Treg) cells develop severe tissue
      inflammation in lung, skin, and liver with premature death, whereas the intestine
      remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg
      for the activation of T cells and the development of intestinal inflammation.
      METHODS: Foxp3-GFP-DTR (human diphtheria toxin receptor) C57BL/6 mice allow
      elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin). The influence
      of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell
      transfer colitis model in Rag-/- C57BL/6 mice and the acute DSS-colitis model.
      RESULTS: Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to
      dramatic weight loss and death of mice by day 28. After 10 days of depletion of
      Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts
      of IFN-gamma, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from
      Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag
      /- C57BL/6 mice. However, administration of DTx between days 14 and 18 after T
      cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight
      loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg
      depletion consecutively increased inflammatory cytokine production. Further, the
      depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute
      dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T
      cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory
      cytokines. CONCLUSION: Intermittent depletion of Foxp3+ Treg aggravates
      intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for
      the balance at the mucosal surface of the intestine.

PMID- 22849661
TI  - Optimal MHC-II-restricted tumor antigen presentation to CD4+ T helper cells: the
      key issue for development of anti-tumor vaccines.
AB  - Present immunoprevention and immunotherapeutic approaches against cancer suffer
      from the limitation of being not "sterilizing" procedures, as very poor
      protection against the tumor is obtained. Thus newly conceived anti-tumor
      vaccination strategies are urgently needed. In this review we will focus on ways
      to provide optimal MHC class II-restricted tumor antigen presentation to CD4+ T
      helper cells as a crucial parameter to get optimal and protective adaptive immune
      response against tumor. Through the description of successful preventive or
      therapeutic experimental approaches to vaccinate the host against the tumor we
      will show that optimal activation of MHC class II-restricted tumor specific CD4+
      T helper cells can be achieved in various ways. Interestingly, the success in
      tumor eradication and/or growth arrest generated by classical therapies such as
      radiotherapy and chemotherapy in some instances can be re-interpreted on the
      basis of an adaptive immune response induced by providing suitable access of
      tumor-associated antigens to MHC class II molecules. Therefore, focussing on
      strategies to generate better and suitable MHC class II-restricted activation of
      tumor specific CD4+ T helper cells may have an important impact on fighting and
      defeating cancer.

PMID- 22849663
TI  - Bone grafting, corticotomy, and orthodontics: treatment of cleft alveolus in a
      chinese cohort.
AB  - Objective : A multimodal therapy was applied to solve a set of related problems
      including collapse of the posterior segment, high level gingival margin of
      canine, and resorption of grafted bone in a cohort of Chinese youngsters with
      cleft lip and palate. This study aimed to evaluate the benefits of this treatment
      procedure. Methods : Thirty patients with unilateral cleft lip and palate were
      included in this prospective study. All patients had previously undergone only
      cleft lip and palate repair and presented with alveolar cleft and an obvious step
      in the gingival margin between the canine tooth and the teeth beside it. A
      multimodal therapy that included bone grafting, corticotomy, and orthodontics was
      applied to solve these problems. Grafted bone volume, parallelism of the roots,
      root resorption, gingival margin, and mobility of the canine on the cleft side
      were established before surgery, 1 week after surgery, and after straightening of
      the canine. Results : Less than 25% of the grafted bone was reabsorbed in 25 of
      the 30 patients, while less than 50% was resorbed in the remaining five. The
      roots of the canines on the cleft side were mostly parallel to the adjacent
      teeth. Root resorption and mobility of the canines were slight. The difference in
      the gingival margin between the canines on the cleft side and the other side was
      small. Conclusions : Canines moved into the grafted bone safely and effectively,
      thus achieving a normal gingival margin and retaining grafted bone volume in one
      operation. 

PMID- 22849662
TI  - Prospective evaluation of a clinical practice guideline for diagnosis of
      appendicitis in children.
AB  - OBJECTIVES: The objective was to assess the performance of a clinical practice
      guideline for evaluation of possible appendicitis in children. The guideline
      incorporated risk stratification, staged imaging, and early surgical involvement
      in high-risk cases. METHODS: The authors prospectively evaluated the clinical
      guideline in one pediatric emergency department (ED) in a general teaching
      hospital. Patients were risk-stratified based on history, physical examination
      findings, and laboratory results. Imaging was ordered selectively based on risk
      category, with ultrasound (US) as the initial imaging modality. Computed
      tomography (CT) was ordered if the US was negative or indeterminate. Surgery was
      consulted before imaging in high-risk patients. RESULTS: A total of 475 patients
      were enrolled. Of those, 193 (41%) had appendicitis. No low-risk patient had
      appendicitis. Medium-risk patients had a 19% rate of appendicitis, and 83% of
      high-risk patients had appendicitis. Factors associated with an increased
      likelihood of appendicitis included decreased bowel sounds; rebound tenderness;
      and presence of psoas, obturator, or Rovsing's signs. Of the 475 patients, 276
      (58%) were managed without a CT scan. Seventy-one of the 193 (37%) patients with
      appendicitis went to the operating room without any imaging. The rate of missed
      appendicitis was 2%, and the rate of negative appendectomy was 1%. CONCLUSIONS:
      The clinical practice guideline performed well in a general teaching hospital.
      Rates of negative appendectomy and missed appendicitis were low and 58% of
      patients were managed without a CT scan.

PMID- 22849664
TI  - Measuring patient activation in The Netherlands: translation and validation of
      the American short form Patient Activation Measure (PAM13).
AB  - BACKGROUND: The American short form Patient Activation Measure (PAM) is a 13-item
      instrument which assesses patient (or consumer) self-reported knowledge, skills
      and confidence for self-management of one's health or chronic condition. In this
      study the PAM was translated into a Dutch version; psychometric properties of the
      Dutch version were established and the instrument was validated in a panel of
      chronically ill patients. METHODS: The translation was done according to WHO
      guidelines. The PAM 13-Dutch was sent to 4178 members of the Dutch National Panel
      of people with Chronic illness or Disability (NPCD) in April 2010 (study A) and
      again to a sub sample of this group (N = 973) in June 2010 (study B). Internal
      consistency, test-retest reliability and cross-validation with the SBSQ-D (a
      measure for Health literacy) were computed. The Dutch results were compared to
      similar Danish and American data. RESULTS: The psychometric properties of the PAM
      13-Dutch were generally good. The level of internal consistency is good (alpha =
      0.88) and item-rest correlations are moderate to strong. The Dutch mean PAM score
      (61.3) is comparable to the American (61.9) and lower than the Danish (64.2). The
      test-retest reliability was moderate. The association with Health literacy was
      weak to moderate. CONCLUSIONS: The PAM-13 Dutch is a reliable instrument to
      measure patient activation. More research is needed into the validity of the
      Patient Activation Measure, especially with respect to a more comprehensive
      measure of Health literacy.

PMID- 22849665
TI  - Reductive nitro-Mannich route for the synthesis of 1,2-diamine containing
      indolines and tetrahydroquinolines.
AB  - A one-pot, 1,4-hydride addition nitro-Mannich reaction between a set of
      nitroalkenes 3 and a wide range of N-p-methoxyphenyl-protected aldimines, derived
      from alkyl, aryl and heteroaryl aldehydes, followed by Zn/HCl reduction leads to
      stereochemically defined 1,2-diamines. These underwent palladium-catalyzed
      cyclization and depending upon the presence or not of the trifluoroacetamide
      protecting group gave either tetrahydroquinolines 18 or indolines 14 in high
      overall yield and diastereoselectivity (19 examples each). In each case, the more
      nucleophilic pendant amine cyclizes to give a benzofused saturated heterocyclic 5
      or 6-membered ring, with an additional vicinal amino stereocenter in each.

PMID- 22849666
TI  - Trunk postural demands of occupational activities of some merchant pregnant women
      in Benin, West Africa.
AB  - Strenuous physical work puts expectant mothers at risk of experiencing back pain
      during the gestational months. Pregnant women in Benin perform physically
      demanding occupational tasks that include the lifting and carriage of heavy loads
      on their heads for commercial activities. A large percentage of pregnant subjects
      (58%) reported having back pain episodes since the start of their pregnancy.
      However, the mean Oswestry score of the affected participants was relatively low
      with a mean score of 0.2 (SD: 0.12), on a scale form 0 to 1. An evaluation of the
      postural demands of the occupational activities of these women revealed that they
      performed on average 328 trunk flexions at angles exceeding 60 degrees , with 66
      of these flexions sustained for more than 4 s, during the average 7.9 h where
      trunk postures were recorded. They also spent on average 36% of the recording
      time at trunk flexion angles larger than 20 degrees . These results show that the
      merchant pregnant women in the Porto-Novo area in Benin are at great risk for
      developing back disorders during pregnancy. PRACTITIONER SUMMARY: Results will
      make a first contribution to the literature by identifying the stressful postures
      adopted during a typical day. The findings of this study can help in the
      development of preventative concepts and postural modification techniques to
      decrease the occurrence of back pain during pregnancy for women in Benin.

PMID- 22849667
TI  - Pharmacokinetic and clinical evaluation of esomeprazole and ASA for the
      prevention of gastroduodenal ulcers in cardiovascular patients.
AB  - INTRODUCTION: Low-dose aspirin (ASA, 75 - 325 mg/day) is widely used for the
      primary and secondary prevention of cardiovascular (CV) diseases. However, the
      value of primary prevention ASA is uncertain as the reduction in occlusive events
      needs to be weighed against the significant increase in major bleedings.
      Prevention with antisecretory drugs has been proposed to reduce the incidence of
      ASA-induced gastrointestinal (GI) bleedings, but non-adherence to gastro
      protection is of concern, as it significantly increases the risk of upper GI
      adverse events. Beside patients and physicians education, one approach to
      overcome non-adherence is the development of fixed-dose combination. AREA
      COVERED: This review explores the results of clinical studies on the influence of
      the combination esomeprazole (ESA) and ASA on pharmacokinetic (PK) parameters,
      and the role for such combination in prevention of CV events in patients at risk
      of gastric ulcers. EXPERT OPINION: Patients at risk of ASA-induced gastroduodenal
      ulcer might benefit from a fixed ASA and proton pump inhibitor (PPI) combination.
      PK and PD parameters suggest there is no significant interaction between these
      drugs. Nevertheless, attention must be paid on the appropriate use of such
      combination, that is, still balancing the risk:benefit ratio in a real-life
      setting, and any increase in the proportion of patients receiving ASA and PPI
      should be considered as a warning signal.

PMID- 22849670
TI  - Sectional anatomic and magnetic resonance imaging features of the head of
      juvenile loggerhead sea turtles (Caretta caretta).
AB  - OBJECTIVE: To compare anatomic features of cross-sectional specimens with those
      of MRI images of the heads of loggerhead sea turtles (Caretta caretta). ANIMALS:
      5 cadavers of juvenile female loggerhead sea turtles. PROCEDURES: Spin-echo T1
      weighted and T2-weighted MRI scans were obtained in sagittal, transverse, and
      dorsal planes with a 0.2-T magnet and head coil. Head specimens were grossly
      dissected and photographed. Anatomic features of the MRI images were compared
      with those of gross anatomic sections of the heads from 4 of these turtles.
      RESULTS: In the MRI images, anatomic details of the turtles' heads were
      identified by the characteristics of signal intensity of various tissues.
      Relevant anatomic structures were identified and labeled on the MRI images and
      corresponding anatomic sections. CONCLUSIONS AND CLINICAL RELEVANCE: The MRI
      images obtained through this study provided valid information on anatomic
      characteristics of the head in juvenile loggerhead sea turtles and should be
      useful for guiding clinical evaluation of this anatomic region in this species.

PMID- 22849668
TI  - Protective role of AT(2) and B(1) receptors in kinin B(2)-receptor-knockout mice
      with myocardial infarction.
AB  - AT(2)Rs [AngII (angiotensin II) type 2 receptors] contribute to the
      cardioprotective effects of angiotensin II receptor blockers, possibly via kinins
      acting on the B(1)R (B(1) receptor) and B(2)R (B(2) receptor). Recent studies
      have shown that a lack of B(2)R up-regulates B(1)R and AT(2)R; however, the
      pathophysiological relevance of such an event remains unclear. We hypothesized
      that up-regulation of AT(2)R and B(1)R compensates for the loss of B(2)R.
      Blockade of AT(2)R and/or B(1)R worsens cardiac remodelling and dysfunction
      following MI (myocardial infarction) in B(2)R(-/-) (B(2)-receptor-knockout mice).
      B(2)R(-/-) mice and WT (wild-type) controls were subjected to sham MI or MI and
      treated for 4 weeks with (i) vehicle, (ii) a B(1)R-ant (B(1)R antagonist; 300
      MUg/kg of body weight per day), (iii) an AT(2)R-ant [AT(2) receptor antagonist
      (PD123319); 20 mg/kg of body weight per day], or (iv) B(1)R-ant+AT(2)R-ant.
      B(2)R(-/-) mice had a greater MCSA (myocyte cross-sectional area) and ICF
      (interstitial collagen fraction) at baseline and after MI compared with WT
      controls. Cardiac function and increase in macrophage infiltration, TGFbeta(1)
      (transforming growth factor beta(1)) expression and ERK1/2 (extracellular-signal
      regulated kinase 1/2) phosphorylation post-MI were similar in both strains.
      Blockade of AT(2)R or B(1)R worsened cardiac remodelling, hypertrophy and
      dysfunction associated with increased inflammation and ERK1/2 phosphorylation and
      decreased NO excretion in B(2)R(-/-) mice, which were exacerbated by dual
      blockade of B(1)R and AT(2)R. No such effects were seen in WT mice. Our results
      suggest that, in the absence of B(2)R, both B(1)R and AT(2)R play important
      compensatory roles in preventing deterioration of cardiac function and
      remodelling post-MI possibly via suppression of inflammation, TGFbeta(1) and
      ERK1/2 signalling.

PMID- 22849671
TI  - Glycohistochemical characterization of histologically normal nasal mucosa and
      enzootic nasal tumor of sheep.
AB  - OBJECTIVE: To determine glycohistochemical characteristics of enzootic nasal
      tumors (ENTs) of sheep, compare results for ENT with those of histologically
      normal nasal mucosa of sheep, and identify the histologic origin of ENT. SAMPLE:
      ENT and nasal mucosa samples obtained from cadavers of 5 adult Lacaune sheep with
      ENT and 5 Lacaune sheep unaffected by ENT, respectively. PROCEDURES: Samples of
      ENT and nasal mucosa were collected from cadavers of sheep and sectioned.
      Conventional and lectin histochemical analyses were used to identify
      glycoconjugates in tissue sections on the basis of their principal chemical
      groups and principal terminal or internal oligosaccharidic glucidic residues,
      respectively. RESULTS: ENTs had papillary and tubular portions. Cells in the
      papillary portion of ENTs had secretion and surface glycoconjugates, which
      included sulfated glycosaminoglycans and neutral and sialilated glycoproteins.
      Cells in the tubular portion of ENTs had surface glycoconjugates, which included
      neutral and sialilated glycoproteins. Both portions of ENTs had C(4)-acetylated
      sialoderivatives that were not detected in sections of histologically normal
      nasal mucosa. CONCLUSIONS AND CLINICAL RELEVANCE: The papillary portion of ENTs
      in sheep may originate from respiratory glands and goblet cells. The tubular
      portion of ENTs in sheep may originate from olfactory glands. Presence of C(4)
      acetylated sialoderivatives in cells of ENTs could confer resistance against
      pathogens to those cells.

PMID- 22849672
TI  - Use of electrical stimulation to monitor lumbosacral epidural and intrathecal
      needle placement in rabbits.
AB  - OBJECTIVE: To determine the minimal electric threshold of neurostimulation
      dorsally and ventrally to the interarcuate ligament in the lumbosacral area
      necessary to cause muscle contraction of the hind limb or tail and determine
      whether a continuous electrical stimulation applied to an insulated needle during
      lumbosacral epidural needle placement could be used to distinguish the epidural
      from the intrathecal space in rabbits. ANIMALS: 24 New Zealand white rabbits.
      PROCEDURES: Rabbits received iohexol (0.2 mL/kg) either dorsally (group 1) or
      ventrally to the interarcuate ligament in the lumbosacral area (groups 2 and 3).
      Correct placement of the needle was determined by use of the loss of resistance
      to injection technique (group 2) or a continuous electrical stimulation (group 3)
      and confirmed by examination of the iohexol distribution pattern on radiographs.
      RESULTS: In all rabbits of group 1, iohexol was injected in the lumbosacral area,
      outside the epidural space. In groups 2 and 3, iohexol was injected
      intrathecally. No pure iohexol epidural migration of iohexol was observed. Mean
      +/- SD minimal electric threshold to elicit a motor response was 1.2 +/- 0.3 mA,
      0.3 +/- 0.1 mA, and 0.3 +/- 0.1 mA in groups 1, 2, and 3, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Neurostimulation was a useful technique to
      determine correct intrathecal needle placement in rabbits but failed to detect
      the lumbosacral epidural space when the common technique, used in dogs and cats
      for the lumbosacral epidural approach, was used.

PMID- 22849673
TI  - Pharmacokinetics after oral and intravenous administration of a single dose of
      tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).
AB  - OBJECTIVE: To determine pharmacokinetics after IV and oral administration of a
      single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona
      ventralis). ANIMALS: 9 healthy adult Hispaniolan Amazon parrots (3 males, 5
      females, and 1 of unknown sex). PROCEDURES: Tramadol (5 mg/kg, IV) was
      administered to the parrots. Blood samples were collected from -5 to 720 minutes
      after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg)
      was orally administered to parrots. Blood samples were collected from -5 to 1,440
      minutes after administration. Three formulations of oral suspension (crushed
      tablets in a commercially available suspension agent, crushed tablets in sterile
      water, and chemical-grade powder in sterile water) were evaluated. Plasma
      concentrations of tramadol and its major metabolites were measured via high
      performance liquid chromatography. RESULTS: Mean plasma tramadol concentrations
      were > 100 ng/mL for approximately 2 to 4 hours after IV administration of
      tramadol. Plasma concentrations after oral administration of tramadol at a dose
      of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration
      at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for
      approximately 6 hours after administration. Oral administration of the suspension
      consisting of the chemical-grade powder resulted in higher plasma tramadol
      concentrations than concentrations obtained after oral administration of the
      other 2 formulations; however, concentrations differed significantly only at 120
      and 240 minutes after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Oral
      administration of tramadol at a dose of 30 mg/kg resulted in plasma
      concentrations (> 100 ng/mL) that have been associated with analgesia in
      Hispaniolan Amazon parrots.

PMID- 22849674
TI  - Antinociceptive effects after oral administration of tramadol hydrochloride in
      Hispaniolan Amazon parrots (Amazona ventralis).
AB  - OBJECTIVE: To evaluate antinociceptive effects on thermal thresholds after oral
      administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona
      ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. PROCEDURES: 2
      crossover experiments were conducted. In the first experiment, 15 parrots
      received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control
      suspension) administered orally. In the second experiment, 11 parrots received 2
      treatments (tramadol hydrochloride [30 mg/kg] and a control suspension)
      administered orally. Baseline thermal foot withdrawal threshold was measured 1
      hour before drug or control suspension administration; thermal foot withdrawal
      threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both
      experiments) and also at 9 hours (second experiment only). RESULTS: For the first
      experiment, there were no overall effects of treatment, hour, period, or any
      interactions. For the second experiment, there was an overall effect of
      treatment, with a significant difference between tramadol hydrochloride and
      control suspension (mean change from baseline, 2.00 degrees  and -0.09 degrees C,
      respectively). There also was a significant change from baseline for tramadol
      hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9
      hours after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Tramadol at a
      dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon
      parrots. This dose was necessary for induction of significant and sustained
      analgesic effects, with duration of action up to 6 hours. Further studies with
      other types of noxious stimulation, dosages, and intervals are needed to fully
      evaluate the analgesic effects of tramadol hydrochloride in psittacines.

PMID- 22849675
TI  - Evaluation of intersegmental vertebral motion during performance of dynamic
      mobilization exercises in cervical lateral bending in horses.
AB  - OBJECTIVE: To identify differences in intersegmental bending angles in the
      cervical, thoracic, and lumbar portions of the vertebral column between the end
      positions during performance of 3 dynamic mobilization exercises in cervical
      lateral bending in horses. ANIMALS: 8 nonlame horses. PROCEDURES: Skin-fixed
      markers on the head, cervical transverse processes (C1-C6) and spinous processes
      (T6, T8, T10, T16, L2, L6, S2, and S4) were tracked with a motion analysis system
      with the horses standing in a neutral position and in 3 lateral bending positions
      to the left and right sides during chin-to-girth, chin-to-hip, and chin-to-tarsus
      mobilization exercises. Intersegmental angles for the end positions in the
      various exercises performed to the left and right sides were compared. RESULTS:
      The largest changes in intersegmental angles were at C6, especially for the chin
      to-hip and chin-to-tarsus mobilization exercises. These exercises were also
      associated with greater lateral bending from T6 to S2, compared with the chin-to
      girth mobilization or neutral standing position. The angle at C1 revealed
      considerable bending in the chin-to-girth position but not in the 2 more caudal
      positions. CONCLUSIONS AND CLINICAL RELEVANCE: The amount of bending in different
      parts of the cervical vertebral column differed among the dynamic mobilization
      exercises. As the horse's chin moved further caudally, bending in the caudal
      cervical and thoracolumbar regions increased, suggesting that the more caudal
      positions may be particularly effective for activating and strengthening the core
      musculature that is used to bend and stabilize the horse's back.

PMID- 22849676
TI  - Validation of an equine inertial measurement unit system in clinically normal
      horses during walking and trotting.
AB  - OBJECTIVE: To validate an equine inertial measurement unit (IMU) system rigidly
      attached to a hoof against a 3-D optical kinematics system in horses during
      walking and trotting. ANIMALS: 5 clinically normal horses. PROCEDURES: 5 swing
      phases of the hooves of the right forelimb and hind limb were collected via both
      3-D optical and IMU systems from 5 horses during walking and trotting. Linear and
      angular positions, velocities, and accelerations were compared between the 2
      systems. RESULTS: Of the 55 variables compared between the 2 systems, 25 had high
      correlations (r > 0.8) and 18 had moderate correlations (r > 0.5). Root mean
      squared errors were lowest in the sagittal plane and orientation (1.1 to 4.4 cm
      over a range of 1.5 to 1.9 m in the cranial-caudal direction and 2.5 degrees  to
      3.5 degrees  over a range of 88 degrees  to 110 degrees  rotating around the
      medial-lateral axis). There were more differences between the 2 systems during
      small changes in motion, such as in the medial-lateral and proximal-distal
      directions and in the angular measures around the cranial-caudal and proximal
      distal axes. CONCLUSIONS AND CLINICAL RELEVANCE: The equine IMU system may be
      appropriate for rigid attachment to a hoof of a horse and use in examination of
      linear and angular motion in the sagittal plane of the hoof during the swing
      phase while walking and trotting. Although promising in many respects, the IMU
      system cannot currently be considered clinically useful for lameness evaluation
      because of limitations in accuracy, attachment method, and lack of stance phase
      evaluation.

PMID- 22849677
TI  - Kinetic and kinematic analysis of the right hind limb during trotting on a
      treadmill in Labrador Retrievers presumed predisposed or not predisposed to
      cranial cruciate ligament disease.
AB  - OBJECTIVE: To identify gait characteristics during trotting on a treadmill in
      nonlame Labrador Retrievers presumed predisposed or not predisposed to cranial
      cruciate ligament disease (CCLD). ANIMALS: Clinically normal Labrador Retrievers
      presumed predisposed (n = 10) or not predisposed (7) to CCLD. PROCEDURES: The
      right hind limb of each dog was classified by use of a predictive score equation
      that combined tibial plateau angle and femoral anteversion angle as presumed
      predisposed (high score [> -1.5]) or not predisposed (low score [<= -1.5]) to
      CCLD. Tarsal joint, stifle joint, and hip joint kinematics, net moments, and
      powers were computed. RESULTS: The stifle joint was held at a greater degree of
      flexion in limbs presumed predisposed to CCLD (130.9 degrees  vs 139.3 degrees ).
      More power was generated by muscles acting on the stifle joint in the early
      stance phase of limbs presumed to be predisposed to CCLD (2.93 vs 1.64 W/kg). The
      tarsal joint did not reach the same degree of extension in limbs presumed
      predisposed to CCLD, compared with that in limbs presumed not predisposed to CCLD
      (179.0 degrees  vs 161.0 degrees ). Velocity, stance time, vertical and
      craniocaudal forces, angular velocities, and net joint muscle moments did not
      differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Gait mechanics of dogs
      with high (> -1.5) and low (<= -1.5) tibial plateau angle and femoral anteversion
      angle scores were characterized on a treadmill, which may help in the
      identification of dogs predisposed to CCLD.

PMID- 22849678
TI  - Influence of serotype, cell type, tissue composition, and time after inoculation
      on gene expression in recombinant adeno-associated viral vector-transduced equine
      joint tissues.
AB  - OBJECTIVE: To evaluate transduction efficiency of gene therapy for treatment of
      osteoarthritis in horses. SAMPLE: Cartilage and synovial tissues were aseptically
      collected from the stifle joints of 3 Thoroughbreds; horses were 3, 7, and 12
      years old and free from sepsis and long-term drug treatment and were euthanized
      for reasons unrelated to joint disease. PROCEDURES: Gene transfer experiments
      were performed with 8 recombinant adeno-associated viral vector (rAAV) serotypes
      in monolayer-cultured equine chondrocytes, synovial cells, and mesenchymal
      stromal cells and in cartilage and synovial tissues. RESULTS: Serotypes rAAV2/5
      and rAAV2/2 yielded the highest transduction efficiency in cultured cells 6 days
      after transduction. Synovial cells and mesenchymal stromal cells were more
      readily transduced than were chondrocytes. Serotype rAAV2/6.2 yielded the highest
      rate of gene expression in both cartilage and synovial tissues at 6 days after
      inoculation. However, at 30 and 60 days after inoculation, gene expression of
      serotypes rAAV2/2 and rAAV2/5 surpassed that of rAAV2/6.2 and all other
      serotypes. CONCLUSIONS AND CLINICAL RELEVANCE: Maximally expressing serotypes
      changed between 6 and 30 days in tissues; however, the most efficient serotypes
      for transduction of joint cells over time were also the most efficient serotypes
      for transduction of joint tissues. In addition, the low transduction efficiency
      of articular cartilage tissue was paralleled by a low transduction efficiency of
      isolated chondrocytes. This suggested that the typically low transduction
      efficiency of articular cartilage may be attributable in part to the low
      transduction efficiency of the chondrocytes and not solely a result of the dense
      cartilage matrix.

PMID- 22849679
TI  - Sex hormone regulation of collagen concentrations in cranial cruciate ligaments
      of sexually immature male rabbits.
AB  - OBJECTIVE: To investigate the effects of gonadectomy on collagen homeostasis in
      cranial cruciate ligaments of male rabbits. ANIMALS: 30 sexually immature (16
      week-old) male New Zealand White rabbits. PROCEDURES: Rabbits were randomly
      assigned to 5 groups of 6 rabbits each: sexually intact, placebo (control group);
      castrated, placebo; castrated, testosterone; castrated, dihydrotestosterone; and
      castrated, 17beta-estradiol (E(2)). Control rabbits underwent a sham operation,
      and all other rabbits underwent gonadectomy. At the time of gonadectomy, the
      placebo and sex hormones were administered via slow-release pellets implanted
      subcutaneously as assigned. After 21 days of hormone supplementation,
      measurements were obtained of serum testosterone and E(2) concentrations,
      ligament collagen characteristics, and androgen receptor, estrogen receoptor
      alpha, and matrix metalloproteinase expression. RESULTS: Following gonadectomy
      and hormone supplementation, the treatment groups differed in serum testosterone
      and E(2) concentrations to various degrees. Collagen concentrations were lower
      and fiber diameters higher in the absence of sex hormones, in association with
      the degrees of estrogen receptor a and androgen receptor expression. Although
      differences were detected among the groups in matrix metalloproteinase
      expression, these differences were not significant. CONCLUSIONS AND CLINICAL
      RELEVANCE: Sex hormones appeared to play a role in cranial cruciate ligament
      homeostasis in male rabbits. Physiologic changes triggered by the lack of sex
      hormones following gonadectomy in sexually immature rabbits may potentially
      predispose those rabbits to orthopedic injuries.

PMID- 22849680
TI  - Serum cobalamin, urine methylmalonic acid, and plasma total homocysteine
      concentrations in Border Collies and dogs of other breeds.
AB  - OBJECTIVE: To determine reference ranges for serum cobalamin (Cbl), urine
      methylmalonic acid (uMMA), and plasma total homocysteine (tHcys) concentrations
      and to compare values for healthy control dogs with values for Border Collies
      (BCs), a breed in which hereditary cobalamin deficiency has been identified.
      ANIMALS: 113 BCs, 35 healthy control dogs fed a typical diet, and 12 healthy dogs
      fed a bone and raw food diet exclusively. PROCEDURES: Urine and blood samples
      were obtained from each dog and Cbl, uMMA, and tHcys concentrations were
      determined. RESULTS: Reference ranges for Cbl (261 to 1,001 ng/L), uMMA (0 to 4.2
      mmol/mol of creatinine), and tHcys (4.3 to 18.4 MUmol/L) concentrations were
      determined. Four BCs had a Cbl concentration lower than the assay detection limit
      (150 ng/L); median uMMA and tHcys concentrations in these dogs were 4,064
      mmol/mol of creatinine and 51.5 MUmol/L, respectively. Clinical abnormalities
      included stunted growth, lethargy, anemia, and proteinuria. Abnormalities
      improved after administration of cobalamin. Of the 109 healthy BCs with Cbl and
      tHcys concentrations within reference ranges, 41 (37.6%) had a high uMMA
      concentration (range, 5 to 360 mmol/mol). Results for dogs fed raw food were
      similar to those for control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Hereditary
      cobalamin deficiency is a rare disease with various clinical signs. The finding
      of methylmalonic aciduria in healthy eucobalaminemic BCs and BCs with clinical
      signs of Cbl deficiency was surprising and indicated these dogs may have defects
      in intracellular processing of Cbl or intestinal Cbl malabsorption, respectively.
      Studies investigating Cbl absorption and metabolic pathways are warranted.

PMID- 22849681
TI  - Sonographic characteristics of presumptively normal main axillary and superficial
      cervical lymph nodes in dogs.
AB  - OBJECTIVE: To evaluate the B-mode and Doppler ultrasonographic appearance of
      presumptively normal main axillary and large superficial cervical lymph nodes
      (MALNs and SCLNs, respectively) in adult dogs. ANIMALS: 51 healthy adult dogs
      (data from 1 dog were not analyzed). PROCEDURES: For each dog, weight, distance
      from the cranial aspect of the first sternebra to the caudal aspect of the left
      ischiatic tuberosity, and thoracic height and width at the level of the xiphoid
      process were recorded. Via B-mode and Doppler ultrasonography, echogenic
      characteristics, size in relation to body size and weight, and vascular supply of
      the MALNs and the SCLNs were evaluated (1 SCLN in 1 dog was not
      ultrasonographically visible). RESULTS: Most MALNs were clearly margined,
      solitary, and ovoid; echopatterns were homogenous or cortical and hypo- to
      isoechoic, compared with surrounding soft tissues. Size measurements of MALNs
      correlated with dogs' body length, thoracic width and height, and body weight.
      Most SCLNs were clearly margined, fusiform, and hypoechoic (compared with
      surrounding soft tissues) with a cortical or homogenous echopattern. Size
      measurements of SCLNs correlated with dogs' body length, thoracic width and
      height, and body weight. In 50 of the 100 MALNs, an intranodal vascular supply
      was detected; in contrast, an intranodal vascular supply in SCLNs was detected
      infrequently. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that, in
      dogs, anatomically separate lymph nodes have different echogenic and vascular
      characteristics; body size (skeletal length, height, and width), along with body
      weight, were correlated with sizes of presumptively normal MALNs and SCLNs.

PMID- 22849682
TI  - Development of a quantitative multivariable radiographic method to evaluate
      anatomic changes associated with laminitis in the forefeet of donkeys.
AB  - OBJECTIVE: To establish and validate an objective method of radiographic
      diagnosis of anatomic changes in laminitic forefeet of donkeys on the basis of
      data from a comprehensive series of radiographic measurements. ANIMALS: 85
      donkeys with and 85 without forelimb laminitis for baseline data determination; a
      cohort of 44 donkeys with and 18 without forelimb laminitis was used for
      validation analyses. PROCEDURES: For each donkey, lateromedial radiographic views
      of 1 weight-bearing forelimb were obtained; images from 11 laminitic and 2
      nonlaminitic donkeys were excluded (motion artifact) from baseline data
      determination. Data from an a priori selection of 19 measurements of anatomic
      features of laminitic and nonlaminitic donkey feet were analyzed by use of a
      novel application of multivariate statistical techniques. The resultant
      diagnostic models were validated in a blinded manner with data from the separate
      cohort of laminitic and nonlaminitic donkeys. RESULTS: Data were modeled, and
      robust statistical rules were established for the diagnosis of anatomic changes
      within laminitic donkey forefeet. Component 1 scores <= -3.5 were indicative of
      extreme anatomic change, and scores from -2.0 to 0.0 denoted modest change.
      Nonlaminitic donkeys with a score from 0.5 to 1.0 should be considered as at risk
      for laminitis. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the
      radiographic procedures evaluated can be used for the identification, assessment,
      and monitoring of anatomic changes associated with laminitis. Screening
      assessments by use of this method may enable early detection of mild anatomic
      change and identification of at-risk donkeys.

PMID- 22849683
TI  - Gene expression in intestinal mucosal biopsy specimens obtained from dogs with
      chronic enteropathy.
AB  - OBJECTIVE: To characterize mucosal gene expression in dogs with chronic
      enteropathy (CE). ANIMALS: 18 dogs with CE and 6 healthy control dogs.
      PROCEDURES: Small intestinal mucosal biopsy specimens were endoscopically
      obtained from dogs. Disease severity in dogs with CE was determined via
      inflammatory bowel index scores and histologic grading of biopsy specimens. Total
      RNA was extracted from biopsy specimens and microchip array analysis (approx
      43,000 probe sets) and quantitative reverse transcriptase PCR assays were
      performed. RESULTS: 1,875 genes were differentially expressed between dogs with
      CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with
      CE, including neurotensin, fatty acid-binding protein 6, fatty acid synthase,
      aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8,
      whereas few genes were upregulated in dogs with CE, including genes encoding
      products involved in extracellular matrix degradation (matrix metallopeptidases
      1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome
      proliferator-activated receptor gamma, and S100 calcium-binding protein G), iron
      transport (solute carrier family 40 member 1), and immunity (CD96 and
      carcinoembryonic antigen-related cell adhesion molecule [CEACAM] 18). Dogs with
      CE and protein-losing enteropathy had the greatest number of differentially
      expressed genes. Results of quantitative reverse transcriptase PCR assay for
      select genes were similar to those for microchip array analysis. CONCLUSIONS AND
      CLINICAL RELEVANCE: Expression of genes encoding products regulating mucosal
      inflammation was altered in dogs with CE and varied with disease severity. Impact
      for Human Medicine-Molecular pathogenesis of CE in dogs may be similar to that in
      humans with inflammatory bowel disease.

PMID- 22849684
TI  - Evaluation of high-molecular weight adiponectin in horses.
AB  - OBJECTIVE: To characterize adiponectin protein complexes in lean and obese
      horses. ANIMALS: 26 lean horses and 18 obese horses. Procedures-Body condition
      score (BCS) and serum insulin activity were measured for each horse. Denaturing
      and native western blot analyses were used to evaluate adiponectin complexes in
      serum. A human ELISA kit was validated and used to quantify high-molecular weight
      (HMW) complexes. Correlations between variables were made, and HMW values were
      compared between groups. RESULTS: Adiponectin was present as a multimer
      consisting of HMW (> 720-kDa), low-molecular weight (180-kDa), and trimeric (90
      kDa) complexes in serum. All complexes were qualitatively reduced in obese horses
      versus lean horses, but the percentage of complexes < 250 kDa was higher in obese
      versus lean horses. High-molecular weight adiponectin concentration measured via
      ELISA was negatively correlated with serum insulin activity and BCS and was lower
      in obese horses (mean +/- SD, 3.6 +/- 3.9 MUg/mL), compared with lean horses (8.0
      +/- 4.6 MUg/mL). CONCLUSIONS AND CLINICAL RELEVANCE: HMW adiponectin is
      measurable via ELISA, and concentration is negatively correlated with BCS and
      serum insulin activity in horses. A greater understanding of the role of
      adiponectin in equine metabolism will provide insight into the pathophysiology of
      metabolic disease conditions.

PMID- 22849685
TI  - Developmental regulation of the activation of translation initiation factors of
      skeletal muscle in response to feeding in horses.
AB  - OBJECTIVE: To determine whether feeding-induced activation of translation
      initiation factors, specifically protein kinase B, ribosomal protein S6 kinase
      (S6K1), ribosomal protein S6 (rpS6), and eukaryotic initiation factor 4E binding
      protein 1, in horses is affected by age. ANIMALS: 6 yearlings, six 2-year-old
      horses, and 6 mature horses. PROCEDURES: After an 18-hour period of feed
      withholding, horses consumed a high-protein meal (2 g/kg) at time 0 and 30
      minutes (postprandial state) or continued to have feed withheld (postabsorptive
      state). Blood samples were collected for the duration of the experimental
      procedures and used to determine plasma concentrations of glucose, insulin, and
      amino acids. At 90 minutes, biopsy specimens were collected from a gluteal muscle
      and used to measure phosphorylation of translation initiation factors. RESULTS:
      Plasma glucose, insulin, and amino acid concentrations were elevated for the
      postprandial state, compared with results for the postabsorptive state,
      regardless of age. Phosphorylation of protein kinase B, S6K1, rpS6, and
      eukaryotic initiation factor 4E binding protein 1 was increased for the
      postprandial state. There was an effect of age with increased phosphorylation of
      S6K1 at Thr(389) and rpS6 at Ser(235/236) in the yearlings and mature horses,
      compared with results for the 2-year-old horses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Food consumption resulted in an increase in the activation of
      translation initiation factors, with the highest degree of responsiveness in the
      yearlings. This indicated that increased muscle accretion seen during growth
      could be a result of increased rates of muscle protein synthesis in response to a
      meal stimulus.

PMID- 22849686
TI  - Oncolysis of canine tumor cells by myxoma virus lacking the serp2 gene.
AB  - OBJECTIVE: To determine the oncolytic efficacy of an attenuated form of myxoma
      virus lacking the serp2 gene in canine tumor cells. SAMPLE: Primary cells were
      isolated from tumors that were surgically removed from dogs and from connective
      tissue obtained from the cadaver of a dog. Cells of various established cell
      lines from tumors and nontumorous tissues were obtained. PROCEDURES: Experiments
      were performed with cells in monolayer culture. Cell cultures were inoculated
      with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and
      measures of cytopathic effects, viral growth kinetics, and cell death and
      apoptosis were determined. RESULTS: Myxoma viruses replicated in cells of many of
      the primary and established canine tumor cell lines. Canine tumor cells in which
      expression of activated protein kinase B was upregulated were more permissive to
      myxoma virus infection than were cells in which expression of activated protein
      kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more
      cytopathic effects in canine tumor cells because of apoptosis than did wild-type
      myxoma viruses. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study
      indicated myxoma viruses lacking the serp2 gene may be useful for treatment of
      cancer in dogs. Impact for Human Medicine-Results of the present study may be
      useful for development of novel oncolytic treatments for tumors in humans.

PMID- 22849687
TI  - Effects of gemcitabine and gemcitabine in combination with carboplatin on five
      canine transitional cell carcinoma cell lines.
AB  - OBJECTIVE: To evaluate in vitro effects of gemcitabine alone and in combination
      with carboplatin on canine transitional cell carcinoma (TCC) cell lines. SAMPLE:
      In vitro cultures of 5 canine TCC cell lines. PROCEDURES: Cells were treated with
      gemcitabine, carboplatin, or a combination of both at various concentrations.
      Cell proliferation was assessed via a fluorescence-based microplate cell
      proliferation assay. Cell cycle was evaluated via propidium iodide staining, and
      apoptosis was assessed by measurement of caspase 3 and 7 enzymatic activity.
      Synergy between gemcitabine and carboplatin was quantified via combination index
      analyses. RESULTS: Treatment of 5 canine TCC cell lines with gemcitabine or
      carboplatin decreased cell proliferation, increased apoptosis, and induced cell
      cycle arrest. Cell cycle arrest and apoptosis were markedly increased when cell
      lines were treated with both gemcitabine and carboplatin simultaneously or
      sequentially. Order of administration during sequential treatment did not
      consistently affect cell proliferation results in TCC cell lines. When TCC cell
      lines were treated with gemcitabine and carboplatin in combination at
      therapeutically relevant concentrations (gemcitabine concentration, < 10MUM;
      carboplatin concentration, < 250MUM), a significant decrease in cell
      proliferation was observed, compared with cell proliferation following treatment
      with gemcitabine or carboplatin alone. In combination, the effects of gemcitabine
      and carboplatin were synergistic in 3 of 5 cell lines and additive in the other
      2. CONCLUSIONS AND CLINICAL RELEVANCE: Gemcitabine had antitumor effects on
      canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had
      synergistic activity at biologically achievable concentrations.

PMID- 22849688
TI  - Effect of omega-3 polyunsaturated fatty acids and body condition on serum
      concentrations of adipokines in healthy dogs.
AB  - OBJECTIVE: To determine associations between serum concentrations of omega-3
      polyunsaturated fatty acids or body condition and serum concentrations of
      adiponectin, leptin, insulin, glucose, or triglyceride in healthy dogs. ANIMALS:
      62 healthy adult client-owned dogs. PROCEDURES: Body condition score and
      percentage of body fat were determined. Blood samples were collected after food
      was withheld for 12 hours. Serum was harvested for total lipid determination,
      fatty acid analysis, and measurement of serum concentrations of adiponectin,
      leptin, insulin, glucose, and triglyceride. Associations between the outcome
      variables (adiponectin, leptin, insulin, glucose, and triglyceride
      concentrations) and each of several variables (age, sex, percentage of body fat,
      and concentrations of total lipid, alpha-linolenic acid, eicosapentaenoic acid,
      docosapentaenoic acid, and docosahexaenoic acid) were determined. RESULTS: Serum
      concentrations of docosapentaenoic acid were significantly positively associated
      with concentrations of adiponectin and leptin and negatively associated with
      concentrations of triglyceride. Serum concentrations of alpha-linolenic acid were
      significantly positively associated with concentrations of triglyceride. No
      significant associations were detected between serum concentrations of
      eicosapentaenoic acid or docosahexaenoic acid and any of the outcome variables.
      Percentage of body fat was significantly positively associated with
      concentrations of leptin, insulin, and triglyceride but was not significantly
      associated with adiponectin concentration. Age was positively associated with
      concentrations of leptin, insulin, and triglyceride and negatively associated
      with concentrations of adiponectin. Sex did not significantly affect serum
      concentrations for any of the outcome variables. CONCLUSIONS AND CLINICAL
      RELEVANCE: Docosapentaenoic acid may increase serum concentrations of adiponectin
      and leptin and decrease serum triglyceride concentration in healthy dogs.

PMID- 22849690
TI  - Effects of extracellular lactate on production of reactive oxygen species by
      equine polymorphonuclear leukocytes in vitro.
AB  - OBJECTIVE: To evaluate effects of extracellular lactate on viability, shape
      change, lactate metabolism, and reactive oxygen species (ROS) production in
      equine polymorphonuclear leukocytes (PMNs). SAMPLE: PMNs isolated from equine
      venous blood samples. PROCEDURES: PMNs were incubated with 0 to 300mM lactate for
      30 minutes before each experiment. Viability was assessed via trypan blue
      exclusion. Shape change was assessed via flow cytometry and light microscopy.
      Relative quantification of monocarboxylic acid transporter and lactate
      dehydrogenase lactate dehydrogenase (LDH) isotype mRNAs was performed with a real
      time PCR assay. Effects of lactate at a pH of 7.4 to 6.0 on ROS production in
      response to phorbol 12-myristate 13-acetate, opsonized zymosan, or N-formyl
      methionyl-leucyl-phenylalanine was assessed by luminol-dependent
      chemiluminescence. RESULTS: Lactate had no effect on viability of PMNs but did
      alter their size and density. Monocarboxylic acid transporter 1 and lactate
      dehydrogenase B mRNA values were not altered. Monocarboxylic acid transporter 4
      and lactate dehydrogenase A mRNA values were significantly decreased. Lactate
      incubation of cells significantly decreased PMN-derived luminol-dependent
      chemiluminescence and induced different sensitivities to stimulants (phorbol 12
      myristate 13-acetate, opsonized zymosan, and N-formyl-methionyl-leucyl
      phenylalanine). The response ratio to N-formyl-methionyl-leucyl-phenylalanine
      revealed that PMNs were primed by incubation with up to 50mM lactate,
      significantly increasing the production of ROS. Incubation with lactate and
      acidic pH caused a synergistic effect on ROS production. CONCLUSIONS AND CLINICAL
      RELEVANCE: Extracellular lactate potentially has a direct effect on the capacity
      to produce ROS by equine PMNs, which may be associated with alterations in innate
      immune functions within a short period after high-intensity exercise.

PMID- 22849689
TI  - Effects of intramuscular administration of tiletamine-zolazepam with and without
      sedative pretreatment on plasma and serum biochemical values and glucose
      tolerance test results in Japanese black bears (Ursus thibetanus japonicus).
AB  - OBJECTIVE: To establish a safe anesthetic protocol with little effect on blood
      biochemical values and IV glucose tolerance test (IVGTT) results in Japanese
      black bears (Ursus thibetanus japonicus). ANIMALS: 16 captive female Japanese
      black bears (5 to 17 years of age). PROCEDURES: Bears were randomly assigned to 4
      treatment groups (4 bears/group) in which various treatment combinations were
      administered via blow dart: tiletamine HCl and zolazepam HCl (9 mg/kg) alone
      (TZ), TZ (6 mg/kg) and acepromazine maleate (0.1 mg/kg), TZ (6 mg/kg) and
      butorphanol tartrate (0.3 mg/kg), or TZ (3 mg/kg) and medetomidine HCl (40
      MUg/kg). Glucose injection for the IVGTT was started 130 minutes after TZ
      administration. Blood samples were obtained before, at, and intermittently after
      glucose injection for measurement of biochemical variables as well as plasma
      glucose and serum insulin concentrations during the IVGTT. Rectal temperature,
      pulse rate, and respiratory rate were assessed every 15 minutes during the
      experiment. RESULTS: Induction and maintenance of anesthesia were safely achieved
      with little adverse effect on cardiopulmonary function when each of the 4
      anesthetic regimens was used, although mild hypothermia was induced. No
      difference was evident between treatment groups in blood biochemical values.
      Blood glucose and insulin concentration profiles during the IVGTT were similar
      among the bears given TZ, with or without acepromazine or butorphanol, but
      hyperglycemia and hypoinsulinemia developed in bears given TZ with medetomidine.
      CONCLUSIONS AND CLINICAL RELEVANCE: All 4 anesthetic regimens yielded chemical
      restraint without affecting clinical and biochemical values in bears, but
      medetomidine appeared to affect IVGTT results. For this reason, medetomidine
      should not be used when anesthetizing bears for IVGTTs.

PMID- 22849691
TI  - Refractive state following retinal reattachment and silicone oil tamponade in
      dogs.
AB  - OBJECTIVE: To evaluate the refractive error induced by intraocular administration
      of silicone oil (SiO) in dogs. ANIMALS: 47 client-owned dogs evaluated for
      blindness secondary to retinal detachment. PROCEDURES: -3-port pars plana
      vitrectomy with perfluoro-octane and SiO exchange (1,000- or 5,000-centistoke
      SiO) was performed in 1 or both eyes for all dogs (n = 63 eyes), depending on
      which eye or eyes were affected. Dogs were normotensive, had complete oil filling
      of the eyes, and were examined in a standing position for retinoscopic
      examination of both eyes (including healthy eyes). RESULTS: The mean refractive
      error for SiO-filled phakic and pseudophakic eyes was 2.67 and 3.24 D,
      respectively. The mean refractive error for SiO-filled aphakic eyes was 6.50 D.
      Dogs in which 5,000-centistoke SiO was used had consistently greater positive
      refractive errors (mean, 3.45 D), compared with dogs in which 1,000-centistoke
      SiO was used (mean, 2.10 D); however, the difference was nonsignificant. There
      was no significant linear relationship between refractive error and the number of
      days between surgery and retinoscopy. CONCLUSIONS AND CLINICAL RELEVANCE:
      Hyperopia was observed in all dogs that underwent SiO tamponade, regardless of
      lens status (phakic, pseudophakic, or aphakic). Aphakic eyes underwent a myopic
      shift when filled with SiO. Pseudophakic eyes appeared to be more hyperopic than
      phakic eyes when filled with SiO; however, additional investigation is needed to
      confirm the study findings.

PMID- 22849692
TI  - Isolation, characterization, and in vitro proliferation of canine mesenchymal
      stem cells derived from bone marrow, adipose tissue, muscle, and periosteum.
AB  - OBJECTIVE: To isolate and characterize mesenchymal stem cells (MSCs) from canine
      muscle and periosteum and compare proliferative capacities of bone marrow-,
      adipose tissue-, muscle-, and periosteum-derived MSCs (BMSCs, AMSCs, MMSCs, and
      PMSCs, respectively). SAMPLE: -7 canine cadavers. PROCEDURES: -MSCs were
      characterized on the basis of morphology, immunofluorescence of MSC-associated
      cell surface markers, and expression of pluripotency-associated transcription
      factors. Morphological and histochemical methods were used to evaluate
      differentiation of MSCs cultured in adipogenic, osteogenic, and chondrogenic
      media. Messenger ribonucleic acid expression of alkaline phosphatase, RUNX2,
      OSTERIX, and OSTEOPONTIN were evaluated as markers for osteogenic
      differentiation. Passage-1 MSCs were counted at 24, 48, 72, and 96 hours to
      determine tissue-specific MSC proliferative capacity. Mesenchymal stem cell yield
      per gram of tissue was calculated for confluent passage-1 MSCs. RESULTS: 
      Successful isolation of BMSCs, AMSCs, MMSCs, and PMSCs was determined on the
      basis of morphology; expression of CD44 and CD90; no expression of CD34 and CD45;
      mRNA expression of SOX2, OCT4, and NANOG; and adipogenic and osteogenic
      differentiation. Proliferative capacity was not significantly different among
      BMSCs, AMSCs, MMSCs, and PMSCs over a 4-day culture period. Periosteum provided a
      significantly higher MSC yield per gram of tissue once confluent in passage 1
      (mean +/- SD of 19,400,000 +/- 12,800,000 of PMSCs/g of periosteum obtained in a
      mean +/- SD of 13 +/- 1.64 days). CONCLUSIONS AND CLINICAL RELEVANCE: -Results
      indicated that canine muscle and periosteum may be sources of MSCs. Periosteum
      was a superior tissue source for MSC yield and may be useful in allogenic
      applications.

PMID- 22849693
TI  - Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium
      andersonii) orally administered to cattle.
AB  - OBJECTIVE: To determine the toxicokinetics of N
      (methylsuccinimido)anthranoyllycoctonine-type low larkspur alkaloids in beef
      cattle. ANIMALS: 5 Black Angus steers and 35 Swiss Webster mice. PROCEDURES: -Low
      larkspur (Delphinium andersonii) was collected, dried, ground, and administered
      to 5 steers via oral gavage to provide a dose of 12 mg of N-(methylsuccinimido)
      anthranoyllycoctonine alkaloids/kg. Steers were housed in metabolism crates for
      96 hours following larkspur administration; heart rate was monitored
      continuously, and blood samples were collected periodically for analysis of serum
      concentrations of 16-deacetylgeyerline, methyllycaconitine, geyerline, and
      nudicauline and assessment of kinetic parameters. The LD(50) of a total alkaloid
      extract from D andersonii was determined in Swiss Webster mice. RESULTS: -The
      alkaloids were quickly absorbed, with a maximum serum concentration achieved
      within 18 hours after administration. Geyerline and nudicauline coeluted as 1
      peak and were considered together for toxicokinetic analysis. Mean +/- SD
      elimination half-life was 18.4 +/- 4.4 hours, 15.6 +/- 1.5 hours, and 16.5 +/-
      5.1 hours for 16-deacetylgeyerline, methyllycaconitine, and geyerline and
      nudicauline, respectively. There were significant differences in maximum serum
      concentration, amount absorbed, and distribution half-life among the 4 alkaloids.
      The mouse LD(50) was 9.8 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: -Results
      suggested that clinical poisoning was likely to be most severe approximately 18
      hours after exposure. Cattle should be closely monitored for at least 36 hours
      after initial exposure. Additionally, a withdrawal time of approximately 7 days
      would be required to clear > 99% of the toxic alkaloids from the serum of cattle
      that have ingested low larkspur.

PMID- 22849694
TI  - Risk factors for onset of hypothermia in trauma victims: the HypoTraum study.
AB  - INTRODUCTION: Hypothermia is common in trauma victims and is associated with an
      increase in mortality. Its causes are not well understood. Our objective was to
      identify the factors influencing the onset of hypothermia during pre-hospital
      care of trauma victims. METHODS: This was a multicenter, prospective, open,
      observational study in a pre-hospital setting. RESULTS: A total of 448 patients
      were included. Hypothermia (<35  degrees C) on hospital arrival was present in
      64/448 patients (14%). Significant factors associated with the absence of
      hypothermia in a multivariate analysis were no intubation: Odds Ratio: 4.23 (95%
      confidence interval 1.62 to 1.02); RTS: 1.68 (1.29 to 2.20); mobile unit
      temperature: 1.20 (1.04 to 1.38); infusion fluid temperature: 1.17 (1.05 to
      1.30); patient not unclothed: 0.40 (0.18 to 0.90); and no head injury: 0.36 (0.16
      to 0.83). CONCLUSIONS: The key risk factor for the onset of hypothermia was the
      severity of injury but environmental conditions and the medical care provided by
      EMS were also significant factors. Changes in practice could help reduce the
      impact of factors such as infusion fluid temperature and mobile unit temperature.

PMID- 22849695
TI  - Ginsenoside Re ameliorates inflammation by inhibiting the binding of
      lipopolysaccharide to TLR4 on macrophages.
AB  - Ginseng (the root of  Panax ginseng  C.A. Meyer, family Araliaceae), which
      contains protopanaxadiol ginsenoside Rb1 and protopanaxatriol ginsenoside Re as
      main constituents, is frequently used to treat cancer, inflammation, and stress.
      In the preliminary study, protopanaxatriol ginsenoside Re inhibited NF-kappaB
      activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages.
      Therefore, we investigated its anti-inflammatory effect in peptidoglycan (PGN)-,
      LPS-, or tumor necrosis factor-alpha (TNF-alpha)-stimulated peritoneal
      macrophages and, in addition, in LPS-induced systemic inflammation and 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Ginsenoside Re
      inhibited IKK-beta phosphorylation and NF-kappaB activation, as well as the
      expression of proinflammatory cytokines, TNF-alpha and IL-1beta, in LPS
      stimulated peritoneal macrophages, but it did not inhibit them in TNF-alpha- or
      PG-stimulated peritoneal macrophages. Ginsenoside Re also inhibited IRAK-1
      phosphorylation induced by LPS, as well as IRAK-1 and IRAK-4 degradations in LPS
      stimulated peritoneal macrophages. Ginsenoside Re inhibited the binding of Alexa
      Fluor 488-conjugated LPS to TLR4 on peritoneal macrophages. Furthermore,
      ginsenoside Re inhibited the binding of LPS to TLR4 on peritoneal macrophages
      transiently transfected with MyD88 siRNAs. Orally administered ginsenoside Re
      significantly inhibited the expression of IL-1beta and TNF-alpha on LPS-induced
      systemic inflammation and TNBS-induced colitis in mice. Ginsenoside Re inhibited
      colon shortening and myeloperoxidase activity in TNBS-treated mice. Ginsenoside
      Re reversed the reduced expression of tight-junction-associated proteins ZO-1,
      claudin-1, and occludin. Ginsenoside Re (20 mg/kg) inhibited the activation of NF
      kappaB in TNBS-treated mice. On the basis of these findings, ginsenoside Re may
      ameliorate inflammation by inhibiting the binding of LPS to TLR4 on macrophages.

PMID- 22849696
TI  - Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric
      cancer: a case report.
AB  - BACKGROUND: Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely
      rare high-grade neoplasm with poor prognosis. For advanced LMS with distant
      metastasis, the decision as to the choice of the most appropriate therapeutic
      strategy, including chemotherapy and surgery, is difficult. Here, we present an
      unusual case of LMS of the sigmoid colon with liver metastases and gastric
      cancer. The survival of this patient was prolonged by a combined modality therapy
      involving chemotherapy and surgery. CASE PRESENTATION: A 66-year-old woman who
      had been diagnosed with advanced gastric cancer and multiple liver metastases was
      referred to our hospital. The initial treatment with docetaxel and S-1
      considerably reduced both the gastric cancer and liver tumors; consequently we
      performed surgical resection. Pathological examination revealed that no viable
      tumor cells remained in the stomach and chemotherapy resulted in complete
      remission of the gastric cancer. The liver tumors were immunohistochemically
      diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and
      the liver tumors were found to have recurred. The surgically resected sigmoid
      colon and liver tumors were all immunohistochemically diagnosed as LMS. These
      findings indicated that the multiple liver metastases arose from the LMS in the
      sigmoid colon, and that they were accompanied by advanced gastric cancer. We
      performed another surgical resection and administered chemotherapy to treat the
      recurring liver metastases. The patient survived for 4 years and 10 months after
      initial presentation at our hospital. CONCLUSION: Colonic LMS is rare and its
      joint occurrence with gastric cancer is extremely unusual. Although LMS is a high
      grade neoplasm, a multimodal therapeutic approach can increase patient survival
      time even when multiple liver metastases are present.

PMID- 22849697
TI  - Nickel-catalyzed amination of aryl sulfamates and carbamates using an air-stable
      precatalyst.
AB  - A facile nickel-catalyzed method to achieve the amination of synthetically useful
      aryl sulfamates and carbamates is reported. Contrary to most Ni-catalyzed
      amination reactions, this user-friendly approach relies on an air-stable Ni(II)
      precatalyst, which, when employed with a mild reducing agent, efficiently
      delivers aminated products in good to excellent yields. The scope of the method
      is broad with respect to both coupling partners and includes heterocyclic
      substrates.

PMID- 22849699
TI  - Regenerative treatment in spinal cord injury.
AB  - Spinal cord injury is a devastating, traumatic event, and experienced mainly
      among young people. Until the modern era, spinal cord injury was so rapidly fatal
      that no seriously injured persons would survive long enough for regeneration to
      occur. Treatment of spinal cord injury can be summarized as follows: prevent
      further cord injury, maintain blood flow, relieve spinal cord compression, and
      provide secure vertebral stabilization so as to allow mobilization and
      rehabilitation, none of which achieves functional recovery. Previous studies have
      focused on analyzing the pathogenesis of secondary injury that extends from the
      injury epicenter to the periphery, as well as the tissue damage and neural cell
      death associated with secondary injury. Now, there are hundreds of current
      experimental and clinical regenerative treatment studies. One of the most popular
      treatment method is cell transplantation in injured spinal cord. For this purpose
      bone marrow stromal cells, mononuclear stem cells, mesenchymal stem cells,
      embryonic stem cells, neural stem cells, and olfactory ensheathing cells can be
      used. As a result, cell transplantation has become a promising therapeutic option
      for spinal cord injury patients. In this paper we discuss the effectiveness of
      stem cell therapy in spinal cord injury.

PMID- 22849698
TI  - Perception of evidence-based practice and the professional environment of primary
      health care nurses in the Spanish context: a cross-sectional study.
AB  - BACKGROUND: The study of the factors that encourage evidence-based clinical
      practice, such as structure, environment and professional skills, has contributed
      to an improvement in quality of care. Nevertheless, most of this research has
      been carried out in a hospital context, neglecting the area of primary health
      care. The main aim of this work was to assess the factors that influence an
      evidence-based clinical practice among nursing professionals in Primary Health
      Care. METHODS: A multicentre cross-sectional study was designed, taking the 619
      Primary Care staff nurses at the Balearic Islands' Primary Health Care Service,
      as the study population. The methodology applied consisted on a self-administered
      survey using the instruments Evidence-Based Practice Questionnaire (EBPQ) and
      Nursing Work Index (NWI). RESULTS: Three hundred and seventy seven surveys were
      received (60.9% response rate). Self-assessment of skills and knowledge, obtained
      66.6% of the maximum score. The Knowledge/Skills factor obtained the best scores
      among the staff with shorter professional experience. There was a significant
      difference in the Attitude factor (p = 0.008) in favour of nurses with management
      functions, as opposed to clinical nurses.Multivariate analysis showed a
      significant positive relationship between NWI and level of evidence-based
      practice (p < 0,0001). CONCLUSIONS: Institutions ought to undertake serious
      reflection on the lack of skills of senior nurses about Evidence-Based Clinical
      Practice, even when they have more professional experience. Leadership emerge as
      a key role in the transferral of knowledge into clinical practice.

PMID- 22849700
TI  - Platelet rich plasma in xeno-free stem cell culture: the impact of platelet count
      and processing method.
AB  - BACKGROUND: Stem cell culture for regenerative medicine needs platelet rich
      plasma (PRP) as fetal bovine/calf serum (FBS/FCS) substitute. However, the
      various studies used various protocols in preparing and processing the PRP. This
      study aimed to compare and conclude the most effective and efficient protocol.
      METHODS: we searched in vitro studies that used human PRP as FBS/FCS substitute
      to culture human cells, and compared the various available protocols to identify
      the easiest and effective protocols for the preparation of PRP and the release of
      the growth factors (GFs) to support the highest cell growth in stem cell culture.
      RESULTS: ten studies fulfilled the selection criteria and were included in the
      analysis. DISCUSSION: Almost all studies on bone marrow mesenchymal stem cell (BM
      MSC) and adipose stem cell (AT-SC) showed that platelet lysate and/or activated
      platelet releasate were superior or at least the same as either FBS or FCS,
      except for one study that got different results on human AT-SC. Several studies
      showed that either 5% activated PRP (aPRP) or platelet lysate (PL) was sufficient
      to support cell growth, or even better when they were compared to 10% FBS, while
      higher concentrations were counterproductive. However, some studies showed that
      10% aPRP or PL was needed. The difference between studies was due to the
      difference in either the PRP preparation from blood and in the PRP processing to
      release the GFs, which yield various GF concentrations. CONCLUSION: In
      conclusion, studies are needed to reveal the optimal final platelet counts for
      the various PRP processing methods for various kinds of cells. The easiest PRP
      processing is freezing to -20 degrees C followed by thawing, or thrombin
      activation using a final concentration of 100U/mL.

PMID- 22849701
TI  - Potential for statins in the chemoprevention and management of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common, treatment-resistant malignancy with a
      complex molecular pathogenesis. Statins are a widely used class of cholesterol
      lowering drugs with potential anticancer activity. We reviewed the evidence for a
      role of statins in primary and secondary chemoprevention of HCC and slowing the
      course of otherwise incurable primary or recurrent disease. A literature search
      (key words: Statins, hepatocellular carcinoma) conducted to this end, retrieved
      119 references. Here we summarize the history, mechanism of action and
      cardiovascular use of statins and highlight that statins can affect several
      pathways implicated in the development of HCC. In vitro and animal studies
      provide strong evidence for a favorable effect of statins on HCC. However,
      evidence in humans is conflicting. We discuss in full detail the methodological
      strengths and pitfalls of published data including three cohort studies
      suggesting that the use of statins may protect from the development of HCC and of
      a single trial reporting increased survival in those with advanced HCC randomized
      to receive statins. A remarkably hepato-safe class of drugs acting on both
      hepatocyte and endothelial cells, statins also have potentially beneficial
      effects in lowering portal hypertension. In conclusion, there is strong
      experimental evidence that statins are beneficial in chemopreventing and slowing
      the growth of HCC. However, randomized controlled trials are necessary in order
      to investigate the role of statins in the chemoprevention of HCC and in slowing
      the course of otherwise incurable disease in humans.

PMID- 22849702
TI  - A noninvasive mucinous cystic neoplasm with intermediate-grade dysplasia of the
      pancreas and extensive squamous metaplasia: a case report with
      clinicopathological correlation.
AB  - Squamous metaplasia presenting in noninvasive mucinous cystic neoplasm (MCN) of
      the pancreas is extremely rare. We described a case of 39-year-old Chinese female
      with a 5-year history of a slow growing mass in the left upper abdomen and an 18
      month history of surgical incision exudation. The patient underwent
      cystojejunostomy, laparotomy and distal pancreatectomy consecutively because of
      the initial diagnosis of "pancreatic cyst". The histological section showed
      columnar mucin-producing epithelium formed small papillary projections and
      extensively visible squamous metaplasia. Therefore the diagnosis of "noninvasive
      MCN with intermediate-grade dysplasia of the pancreas and extensive squamous
      metaplasia" was made finally. The squamous component of the pancreas may be
      derived from pluripotent stem cells, and may be in association with
      cystojejunostomy. Virtual slides: The virtual slide(s) for this article can be
      found here http://www.diagnosticpathology.diagnomx.eu/vs/1322364365718540.

PMID- 22849704
TI  - An improved synthesis of m-hydroxymexiletine, a potent mexiletine metabolite.
AB  - m-Hydroxymexiletine (MHM), a minor metabolite of the class IB anti-arrhythmic
      drug mexiletine, is about two fold more potent than the parent compound on human
      cardiac voltage-gated sodium channels (hNav1.5), and equipotent to mexiletine on
      human skeletal-muscle voltage-gated sodium channels (hNav1.4). Herein, an
      alternative and simplified synthesis of this promising compound has been
      accomplished. This route, as well as being more efficient, has the advantage,
      over the first, to avoid the use of oxidizing agents, such as the meta
      chloroperoxybenzoic acid.

PMID- 22849703
TI  - Single breath-hold assessment of cardiac function using an accelerated 3D single
      breath-hold acquisition technique--comparison of an intravascular and
      extravascular contrast agent.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) is the current gold standard
      for the assessment of left ventricular (LV) function. Repeated breath-holds are
      needed for standard multi-slice 2D cine steady-state free precession sequences
      (M2D-SSFP). Accelerated single breath-hold techniques suffer from low contrast
      between blood pool and myocardium. In this study an intravascular contrast agent
      was prospectively compared to an extravascular contrast agent for the assessment
      of LV function using a single-breath-hold 3D-whole-heart cine SSFP sequence (3D
      SSFP). METHODS: LV function was assessed in fourteen patients on a 1.5 T MR
      scanner (Philips Healthcare) using 32-channel coil technology. Patients were
      investigated twice using a 3D-SSFP sequence (acquisition time 18-25 s) after
      Gadopentetate dimeglumine (GdD, day 1) and Gadofosveset trisodium (GdT, day 2)
      administration. Image acquisition was accelerated using sensitivity encoding in
      both phase encoding directions (4xSENSE). CNR and BMC were both measured between
      blood and myocardium. The CNR incorporated noise measurements, while the BMC
      represented the coeffiancy between the signal from blood and myocardium [1].
      Contrast to noise ratio (CNR), blood to myocardium contrast (BMC), image quality,
      LV functional parameters and intra-/interobserver variability were compared. A
      M2D-SSFP sequence was used as a reference standard on both days. RESULTS: All 3D
      SSFP sequences were successfully acquired within one breath-hold after GdD and
      GdT administration. CNR and BMC were significantly (p < 0.05) higher using GdT
      compared to GdD, resulting in an improved endocardial definition. Using 3D-SSFP
      with GdT, Bland-Altman plots showed a smaller bias (95% confidence interval LVEF:
      9.0 vs. 23.7) and regression analysis showed a stronger correlation to the
      reference standard (R2 = 0.92 vs. R2 = 0.71), compared to 3D-SSFP with GdD.
      CONCLUSIONS: A single-breath-hold 3D-whole-heart cine SSFP sequence in
      combination with 32-channel technology and an intravascular contrast agent allows
      for the accurate and fast assessment of LV function.

PMID- 22849705
TI  - Cytochrome P450 2A6 phenotyping based on dietary caffeine intake in a Japanese
      population of non-smokers.
AB  - Phenotyping of cytochrome P450 2A6 (CYP2A6) was determined by assessing urinary
      caffeine metabolites in a Japanese population with a high frequency of CYP2A6
      whole-gene deletion (CYP2A6*4). The levels of 1,7-dimethyluric acid (17U), 1
      methylxanthine (1X), and 1,7-dimethylxanthine (17X) were measured in non-smokers
      whose CYP2A6 and NAT2 genotypes had been determined. Low 17U/1X ratios were
      observed in accumulated overnight urine samples of subjects genotyped as
      CYP2A6*4/*4 after caffeine treatment. The individual 17U/1X ratios in spot urine
      samples were almost constant before and 2-8 h after caffeine treatment, with or
      without prior abstention from dietary caffeine. The average 17U/1X ratios
      obtained from subjects with CYP2A6 *4/ *4 or CYP2A6 *1/ *4 genotypes were
      significantly lower than those from subjects with wild-type CYP2A6 *1/ *1 under
      dietary caffeine consumption. The present results suggest that impaired CYP2A6
      function associated with CYP2A6 *4/ *4 could be determined using the 17U/1X
      ratios in spot urine samples under normal dietary caffeine consumption in
      Japanese non-smokers, without the need for additional caffeine administration or
      prior abstention from caffeine.

PMID- 22849706
TI  - Alternatives to lifting concrete masonry blocks onto rebar: biomechanical and
      perceptual evaluations.
AB  - This study examined the use of and barriers to H-block and high lift grouting,
      two alternatives to lifting concrete masonry blocks onto vertical rebar. Peak and
      cumulative shoulder motions were evaluated, as well as adoption barriers: H-block
      cost and stakeholder perceptions. Results indicated that using the alternatives
      significantly decreased peak shoulder flexion (p < 0.001). A case study indicated
      that building cost was higher with H-block, but the difference was less than 2%
      of the total cost. Contractors and specifiers reported important differences in
      perceptions, work norms, and material use and practices. For example, 48% of
      specifiers reported that use of high lift grouting was the contractor's choice,
      while 28% of contractors thought it must be specified. Use of H-block or high
      lift grouting should be considered as methods to reduce awkward upper extremity
      postures. Cost and stakeholders' other perceptions present barriers that are
      important considerations when developing diffusion strategies for these
      alternatives. PRACTITIONER SUMMARY: This study provides information from several
      perspectives about ergonomic controls for a high risk bricklaying task, which
      will benefit occupational safety experts, health professionals and ergonomists.
      It adds to the understanding of shoulder stresses, material cost and stakeholder
      perceptions that will contribute to developing effective diffusion strategies.

PMID- 22849708
TI  - Synthesis, crystal structure, transport, and magnetic properties of novel ternary
      copper phosphides, A2Cu6P5 (A = Sr, Eu) and EuCu4P3.
AB  - Three new ternary copper phosphides, Sr(2)Cu(6)P(5), Eu(2)Cu(6)P(5), and
      EuCu(4)P(3), have been synthesized from the elements in evacuated silica
      capsules. Eu(2)Cu(6)P(5) and Sr(2)Cu(6)P(5) adopt the Ca(2)Cu(6)P(5)-type
      structure, while EuCu(4)P(3) is isostructural to BaMg(4)Si(3) and still remains
      the only representative of this structure type among the ternary Cu pnictides.
      All three materials show metallic conductivity in the temperature range 2 K <= T
      <= 290 K, with no indication for superconductivity. For Eu(2)Cu(6)P(5) and
      EuCu(4)P(3), long-range magnetic order was observed, governed by 4f local moments
      on the Eu atoms with predominant ferromagnetic interactions. While Eu(2)Cu(6)P(5)
      shows a single ferromagnetic transition at T(C) = 34 K, the magnetic behavior of
      EuCu(4)P(3) is more complex, giving rise to three consecutive magnetic phase
      transitions at 70, 43, and 18 K.

PMID- 22849707
TI  - Neuroventilatory efficiency and extubation readiness in critically ill patients.
AB  - INTRODUCTION: Based on the hypothesis that failure of weaning from mechanical
      ventilation is caused by respiratory demand exceeding the capacity of the
      respiratory muscles, we evaluated whether extubation failure could be
      characterized by increased respiratory drive and impaired efficiency to generate
      inspiratory pressure and ventilation. METHODS: Airway pressure, flow, volume,
      breathing frequency, and diaphragm electrical activity were measured in a
      heterogeneous group of patients deemed ready for a spontaneous breathing trial.
      Efficiency to convert neuromuscular activity into inspiratory pressure was
      calculated as the ratio of negative airway pressure and diaphragm electrical
      activity during an inspiratory occlusion. Efficiency to convert neuromuscular
      activity into volume was calculated as the ratio of the tidal volume to diaphragm
      electrical activity. All variables were obtained during a 30-minute spontaneous
      breathing trial on continuous positive airway pressure (CPAP) of 5 cm H2O and
      compared between patients for whom extubation succeeded with those for whom
      either the spontaneous breathing trial failed or for those who passed, but then
      the extubation failed. RESULTS: Of 52 patients enrolled in the study, 35 (67.3%)
      were successfully extubated, and 17 (32.7%) were not. Patients for whom it failed
      had higher diaphragm electrical activity (48%; P < 0.001) and a lower efficiency
      to convert neuromuscular activity into inspiratory pressure and tidal volume (40%
      (P < 0.001) and 53% (P < 0.001)), respectively. Neuroventilatory efficiency
      demonstrated the greatest predictability for weaning success. CONCLUSIONS: This
      study shows that a mixed group of critically ill patients for whom weaning fails
      have increased neural respiratory drive and impaired ability to convert
      neuromuscular activity into tidal ventilation, in part because of diaphragm
      weakness. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01065428.

PMID- 22849710
TI  - Association between child restraint systems use and injury in motor vehicle
      crashes.
AB  - OBJECTIVES: The objective was to estimate the fatal and nonfatal injury risk
      associated with inappropriate or no use of child restraint systems (CRS) for
      children younger than 13 years of age involved in motor vehicle crashes (MVC) in
      the United States. METHODS: This was a cross-sectional study of children aged 0
      to 12 years involved in MVCs based on a nationally representative probability
      sample from 1996 to 2005 in the United States. A total of 7,633 children were
      included in the analysis, weighted to represent 3,798,830 children. Logistic
      regression models were used to examine the association between restraint use and
      fatal or nonfatal injury. RESULTS: In all age groups, failure to use a restraint
      increased the risk of fatal injury (odds ratio [OR] ranged from 9.81 to 23.79,
      all p < 0.05). In children aged 1 to 3 years, inappropriate use of a restraint
      was associated with fatal injury (OR = 6.28, 95% confidence interval [CI] = 2.40
      to 16.48). Restrained children aged 4 to 7 years in rear seats with seat belts
      only (OR = 0.33, 95% CI = 0.11 to 0.94) and infants in front seats using child
      safety seats (OR = 0.26, 95% CI = 0.07 to 0.99) were associated with decreased
      nonfatal but not fatal injury compared to children with the recommended use of
      CRS in the two age groups. CONCLUSIONS: Failure to use child restraints was
      associated with increased fatal injury. Our findings raise questions regarding
      current recommendations for specific CRS use in infants and children 4 to 7 years
      old. Further research is needed to identify the most effective CRS and seating
      location for children of each age.

PMID- 22849709
TI  - Prevalence of vasomotor, psychological, psychosomatic and sexual symptoms in
      perimenopausal and recently postmenopausal Greek women: association with
      demographic, life-style and hormonal factors.
AB  - AIM: To assess the prevalence of climacteric symptoms and their association with
      demographic, life-style and hormonal parameters in Greek peri- and recently
      postmenopausal women. METHODS: 1025 Greek women who were either perimenopausal or
      within their first 5 postmenopausal years participated in this cross-sectional
      observational study. Menopausal symptoms were assessed by the Greene Climacteric
      Scale and were tested for associations with demographic, anthropometric, life
      style and hormonal parameters. RESULTS: 29.8% Of the women reported moderate to
      severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3%
      psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since
      menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well
      as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r = -0.157; p < 0.01)
      correlated with the intensity of menopausal symptoms. In the multivariate
      analysis years since menopause and serum estradiol were the only significant
      predictors of menopausal symptoms (b = -0.158 and b = -0.198, p < 0.001,
      respectively), explaining though only 4.8% of the variance. CONCLUSION: One out
      of three Greek women has moderate to severe climacteric symptoms during the
      menopause transition or the first postmenopausal years. This frequency is
      comparable to other White populations. Menopausal age and endogenous estrogens
      are significant predictors of climacteric symptoms.

PMID- 22849711
TI  - Advances in childhood immunisation in South Africa: where to now? Programme
      managers' views and evidence from systematic reviews.
AB  - BACKGROUND: The Expanded Programme on Immunisation (EPI) is one of the most
      powerful and cost-effective public health programmes to improve child survival.
      We assessed challenges and enablers for the programme in South Africa, as we
      approach the 2015 deadline for the Millennium Development Goals. METHODS: Between
      September 2009 and September 2010 we requested national and provincial EPI
      managers in South Africa to identify key challenges facing EPI, and to propose
      appropriate solutions. We collated their responses and searched for systematic
      reviews on the effectiveness of the proposed solutions; in the Health Systems
      Evidence, Cochrane Library, and PubMed electronic databases. We screened the
      search outputs, selected systematic reviews, extracted data, and assessed the
      quality of included reviews (using AMSTAR) and the quality of the evidence (using
      GRADE) in duplicate; resolving disagreements by discussion and consensus.
      RESULTS: Challenges identified by EPI managers were linked to healthcare workers
      (insufficient knowledge of vaccines and immunisation), the public (anti
      immunisation rumours and reluctance from parents), and health system
      (insufficient financial and human resources). Strategies proposed by managers to
      overcome the challenges include training, supervision, and audit and feedback;
      strengthening advocacy and social mobilisation; and sustainable EPI funding
      schemes, respectively. The findings from reliable systematic reviews indicate
      that interactive educational meetings, audit and feedback, and supportive
      supervision improve healthcare worker performance. Structured and interactive
      communication tools probably increase parents' understanding of immunisation; and
      reminders and recall, use of community health workers, conditional cash
      transfers, and mass media interventions probably increase immunisation coverage.
      Finally, a national social health insurance scheme is a potential EPI financing
      mechanism; however, given the absence of high-quality evidence of effects, its
      implementation should be pilot-tested and the impacts and costs rigorously
      monitored. CONCLUSION: In line with the Millennium Development Goals, we have to
      ensure that our children's right to health, development and survival is
      respected, protected and promoted. EPI is central to this vision. We found
      numerous promising strategies for improving EPI performance in South Africa.
      However, their implementation would need to be tailored to local circumstances
      and accompanied by high-quality monitoring and evaluation. The strength of our
      approach comes from having a strong framework for interventions before looking
      for systematic reviews. Without a framework, we would have been driven by what
      reviews have been done and what is easily researchable; rather than the values
      and preferences of key immunisation stakeholders.

PMID- 22849712
TI  - Phenotypes of CCAAT/enhancer-binding protein beta deficiency: hyperdontia and
      elongated coronoid process.
AB  - OBJECTIVES: This investigation aimed to conduct a case-control study of
      mandibular morphology and dental anomalies to propose a relationship between
      mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein
      beta (CEBPB). MATERIALS AND METHODS: Skulls of CEBPB(-/-), CEBPB(+/-) and
      CEBPB(+/+) mice were inspected with micro-computed tomography. Mandibular
      morphology was assessed with a method of Euclidean distance matrix analysis.
      RESULTS: Elongation of the coronoid process was identified in CEBPB(+/-) (P <=
      0.046) and CEBPB(-/-) 12-month-olds (P <= 0.028) but not in 14-day-olds (P >=
      0.217) and 0-day-olds (P >= 0.189) of either genotype. Formation of supernumerary
      teeth in CEBPB(-/-) adult mice was demonstrated (chi(2) = 6.00, df = 1, P =
      0.014). CONCLUSIONS: CEBPB deficiency was related to elongation of the coronoid
      process and formation of supernumerary teeth. The mandibular and dental
      phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future
      investigations into the influence of CEBPB on mandibular and dental development
      are needed.

PMID- 22849713
TI  - Recent developments in production and biotechnological applications of cold
      active microbial proteases.
AB  - Microbial proteases that occupy a pivotal position with respect to their
      commercial applications are most important hydrolytic enzymes and have been
      studied extensively since the advent of enzymology. Cold-adapted microorganisms
      are potential source of cold-active proteases and they have been isolated from
      the cold regions. Although there are many microbial sources available for
      producing proteases, only few are recognized as commercial producer. Cold-active
      proteases along with their producing microbes are of commercial value and find
      multiple applications in various industrial and biotechnological sectors such as
      additives in detergents, additives in food industries, environmental
      bioremediations, biotransformation and molecular biology applications. Therefore,
      cold-active proteases are the enzymes of choice for many biotechnologists,
      microbiologists, biochemists, environmentalists and biochemical engineers. In the
      present review, we discuss some novel sources along with recent developments in
      production and biotechnological applications of cold-active microbial proteases.

PMID- 22849714
TI  - Trapping of methylglyoxal by curcumin in cell-free systems and in human umbilical
      vein endothelial cells.
AB  - Curcumin, the most active compound of curcuminoids, has been shown to inhibit
      formation of advanced glycation end products (AGEs) in streptozotocin-induced
      diabetic rats. However, little is known on whether curcumin may trap
      methylglyoxal (MGO), a major reactive dicarbonyl compound, to inhibit AGE
      formation. We found that one molecule of curcumin effectively trapped one
      molecule of MGO at a 1:3 ratio at 24 h of incubation under physiological
      conditions (pH 7.4, 37  degrees C). Curcumin decreased N(epsilon)
      (carboxymethyl)lysine (CML) expression in human umbilical vein endothelial cells.
      We further used two curcumin analogues, dimethoxycurcumin (DIMC) and ferulic
      acid, to investigate the possible MGO-trapping mechanism of curcumin. Results
      reveal that DIMC, but not ferulic acid, exhibited MGO-trapping capacity,
      indicating curcumin traps MGO at the electron-dense carbon atom (C10) between the
      two keto carbon groups. Thus, curcumin may prevent MGO-induced endothelial
      dysfunction by directly trapping MGO.

PMID- 22849715
TI  - The role of acid catalysis in the Baeyer-Villiger reaction. A theoretical study.
AB  - Quantum mechanical calculations at the B3LYP/6-311+G(d,p) level have examined the
      overall mechanism of the Baeyer-Villiger (BV) reaction with peroxyacetic acid. A
      series of reactions that include both the addition step and the subsequent alkyl
      group migration step included ketones, acetone, t-butyl methyl ketone,
      acetophenone, cyclohexyl methyl ketone, and cyclohexyl phenyl ketone. The
      combined data suggested that the first step for addition of the peroxyacetic acid
      oxidation catalyst to the ketone carbonyl to produce the Criegee or tetrahedral
      intermediate is rate-limiting and has activation barriers that range from 38 to
      41 kcal/mol without the aid of a catalyst. The rate of addition is markedly
      reduced by the catalytic action of a COOH functionality acting as a donor
      acceptor group affecting both its proton transfer to the ketone C?O oxygen in
      concert with transfer of the OOH proton to the carboxylic acid carbonyl. The
      second or alkyl group migration step has a much reduced activation barrier, and
      its rate is not markedly influenced by acid catalysis. The rate of both steps in
      the BV reaction is greatly influenced by the catalytic action of very strong
      acids.

PMID- 22849716
TI  - The influence of static magnetic field (50 mT) on development and motor behaviour
      of Tenebrio (Insecta, Coleoptera).
AB  - PURPOSE: There is considerable concern about potential effects associated with
      exposure to magnetic fields on organisms. Therefore, duration of pupa-adult
      development and motor behaviour of adults were analyzed in Tenebrio obscursus and
      T. molitor after exposure to static magnetic field (50 mT). MATERIAL AND METHODS:
      The experimental groups were: Control (kept 5 m from the magnets), groups which
      pupae and adults were placed closer to the North pole, or closer to the South
      pole of magnetic dipole. The pupae were exposed to the magnetic field until the
      moment of adult eclosion. The pupa-adult development dynamics were recorded
      daily. Subsequently, behaviour (distance travelled, average speed and immobility)
      of adults exposed to the magnetic field was monitored in a circular open field
      arena. RESULTS: Static magnetic field did not affect pupa-adult developmental
      dynamic of examined Tenebrio species. Exposure to magnetic field did not
      significantly change motor behaviour of T. obscurus adults. The changes in the
      motor behaviour of T. molitor induced by static magnetic field were opposite in
      two experimental groups developed closer to the North pole or closer to the South
      pole of magnetic dipole. CONCLUSION: Static magnetic field (50 mT) did not affect
      on pupa-adult development dynamic of two examined Tenebrio species, but modulated
      their motor behaviour.

PMID- 22849717
TI  - Diffusion-weighted MRI of bone marrow oedema, soft tissue oedema and synovitis in
      paediatric patients: feasibility and initial experience.
AB  - BACKGROUND: MRI has become the mainstay of diagnostic imaging in paediatric
      rheumatology for lesion detection, differential diagnosis and therapy
      surveillance. MR imaging of synovitis, in particular, is indispensable for early
      diagnosis and follow-up in arthritis patients. We used diffusion-weighted MRI
      (DWI) as a new imaging modality in comparison to standard MRI sequences to study
      bone marrow oedema, soft-tissue oedema and synovitis in paediatric patients.
      METHODS: A total of 52 patients (mean age 11 +/- 5 years) with bone marrow oedema
      (n = 31), soft-tissue oedema (n = 20) and synovitis (n = 15) were examined with
      transversal diffusion-weighted single-shot echoplanar imaging in addition to
      standard MR sequences (T2W TIRM, T1W pre- and post-contrast). Diffusion-weighted
      images were used for lesion detection and apparent diffusion coefficient (ADC,
      unit * 10-3 mm2/s) values were measured with ROI technique on ADC maps. RESULTS:
      In 50 of 52 patients, DWI delineated the lesion of interest corresponding to
      pathological signal increase on standard sequences. Mean ADC was 1.60 +/- 0.14
      (range 1.38 - 1.99) in osseous lesions, 1.72 +/- 0.31 (range 1.43 - 2.56) in soft
      tissue oedema and 2.82 +/- 0.24 (range 2.47 - 3.18) for joint effusion (ANOVA p <
      0.001). No significant difference in mean ADC was seen for inflammatory vs. non
      inflammatory lesions. Relative signal intensity of oedema was similar for DWI and
      T2W TIRM. DWI visualised synovial restricted diffusion with a mean ADC of 2.12 +/
      0.45 in 12 of 15 patients with synovitis. CONCLUSIONS: Diffusion-weighted MRI
      reliably visualises osseous and soft tissue oedema, as compared to standard
      sequences. DWI of synovitis is feasible in large joints and presents a novel
      approach to contrast-free imaging of synovitis. Whole-body DWI for chronic non
      bacterial osteomyelitis should be evaluated in future studies.

PMID- 22849718
TI  - Assessment of alternative genotyping strategies to maximize imputation accuracy
      at minimal cost.
AB  - BACKGROUND: Commercial breeding programs seek to maximise the rate of genetic
      gain while minimizing the costs of attaining that gain. Genomic information
      offers great potential to increase rates of genetic gain but it is expensive to
      generate. Low-cost genotyping strategies combined with genotype imputation offer
      dramatically reduced costs. However, both the costs and accuracy of imputation of
      these strategies are highly sensitive to several factors. The objective of this
      paper was to explore the cost and imputation accuracy of several alternative
      genotyping strategies in pedigreed populations. METHODS: Pedigree and genotype
      data from a commercial pig population were used. Several alternative genotyping
      strategies were explored. The strategies differed in the density of genotypes
      used for the ancestors and the individuals to be imputed. Parents, grandparents,
      and other relatives that were not descendants, were genotyped at high-density,
      low-density, or extremely low-density, and associated costs and imputation
      accuracies were evaluated. RESULTS: Imputation accuracy and cost were influenced
      by the alternative genotyping strategies. Given the mating ratios and the numbers
      of offspring produced by males and females, an optimized low-cost genotyping
      strategy for a commercial pig population could involve genotyping male parents at
      high-density, female parents at low-density (e.g. 3000 SNP), and selection
      candidates at very low-density (384 SNP). CONCLUSIONS: Among the selection
      candidates, 95.5% and 93.5% of the genotype variation contained in the high
      density SNP panels were recovered using a genotyping strategy that costs
      respectively, $24.74 and $20.58 per candidate.

PMID- 22849719
TI  - Indication for endoscopic treatment of ulcerative early gastric cancer according
      to depth of ulcer and morphological change.
AB  - BACKGROUND AND AIM: This study was conducted to determine the clinicopathologic
      factors affecting the stage of ulcerative early gastric cancer (EGC), focusing on
      the relationships between cancer stage and degree of endoscopic ulcer depth and
      morphologic changes. METHODS: Medical records of 183 cases of ulcerative EGC who
      had received endoscopic examination two or more times with a minimum interval of
      one week, and who underwent either curative surgery or endoscopic treatment were
      retrospectively reviewed. RESULTS: Change in ulcer morphology at follow-up
      endoscopy was observed in 84 cases (45.9%) with improvement and exacerbation of
      ulcer in 65 (35.5%) and 19 (13.8%) cases, respectively. The presence of type III
      ulcer (P < 0.01), and endoscopic findings suggesting submucosal cancer invasion
      (tumorous bank, fusion of converging folds, hardness or decreased flexibility) (P
      < 0.01), and incomplete ulcer healing (P = 0.036) were independently associated
      with a higher incidence of submucosal cancer invasion. The incidence of lymph
      node metastasis was 14.1%, and undifferentiated histology and presence of
      lymphovascular invasion were significantly associated with a higher incidence of
      lymph node metastasis (P = 0.018 and P = 0.005, respectively). CONCLUSIONS:
      Endoscopic resection with curative intent may be an acceptable option for EGC
      combined with endoscopic ulcer or ulcer scar, but should be restricted to cases
      showing significant improvement in the size and depth of ulcer at follow-up
      endoscopy, and which are not accompanied with deep ulcer more than the thickness
      of adjacent mucosal surface and prominent surrounding mucosal fold change. In
      addition, histologic criteria should meet the conditions of differentiated
      intramucosal cancer without lymphovascular invasion.

PMID- 22849720
TI  - Palladium-catalyzed cascade process consisting of isocyanide insertion and
      benzylic C(sp3)-H activation: concise synthesis of indole derivatives.
AB  - Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade
      process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It
      was found that slow addition of isocyanide is effective for reducing the amount
      of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation.
      The construction of the tetracyclic carbazole skeleton was also achieved by a Pd
      catalyzed domino reaction incorporating alkyne insertion.

PMID- 22849721
TI  - Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and
      SIRT5.
AB  - Carba-NAD is a synthetic compound identical to NAD except for one substitution,
      where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is
      replaced with a methylene group. Because it is inert in nicotinamide displacement
      reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming
      enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic
      targets for the treatment of metabolic diseases and cancers. We report an
      improved carba-NAD synthesis, including a pyrophosphate coupling method that
      proceeds in approximately 60% yield. We also disclose the X-ray crystal
      structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide
      substrate and carba-NAD. These X-ray crystal structures provide critical
      snapshots of the mechanism by which human sirtuins function as protein
      deacylation catalysts.

PMID- 22849722
TI  - Involvement of recently cultured group U2 bacterium in ruminal fiber digestion
      revealed by coculture with Fibrobacter succinogenes S85.
AB  - In a previous study, we reported the ecological significance of uncultured
      bacterial group U2 in the rumen. In this study, the involvement of a recently
      cultured group U2 bacterium, strain R-25, in fiber digestion was tested in
      coculture with the fibrolytic bacterium Fibrobacter succinogenes S85. Dry matter
      (DM) digestion, growth and metabolites were examined in culture using rice straw
      as the carbon source. Although strain R-25 did not digest rice straw in
      monoculture, coculture of strain R-25 and F. succinogenes S85 showed enhanced DM
      digestion compared with that for F. succinogenes S85 monoculture (36.9 +/- 0.6%
      vs. 32.8 +/- 1.3%, P < 0.05). Growth of strain R-25 and production of the main
      metabolites, d-lactate (strain R-25) and succinate (F. succinogenes S85), were
      enhanced in the coculture. Enzyme assay showed increased activities of
      carboxymethylcellulase and xylanase in coculture of strain R-25 and F.
      succinogenes S85. Triculture including strain R-25, F. succinogenes S85 and
      Selenomonas ruminantium S137 showed a further increase in DM digestion (41.8 +/-
      0.8%, P < 0.05) with a concomitant increase in propionate, produced from the
      conversion of d-lactate and succinate. These results suggest that the positive
      interaction between strains R-25 and F. succinogenes S85 causes increased rice
      straw digestion.

PMID- 22849723
TI  - Implementation of HybridArc treatment technique in preoperative radiotherapy of
      rectal cancer: dose patterns in target lesions and organs at risk as compared to
      helical Tomotherapy and RapidArc.
AB  - PURPOSE: HybridArc is a novel treatment technique blending aperture-enhanced
      optimized arcs with discrete IMRT-elements, allowing selection of arcs with a set
      of static IMRT-beams. This study compared this new technique to helical
      Tomotherapy, and RapidArc, in preoperative radiotherapy of rectal cancer.
      MATERIAL AND METHODS: Twelve rectal cancer patients treated consecutively with
      Tomotherapy Hi-Art II system were simulated with HybridArc and RapidArc.
      Treatment plans were designed to deliver homogeneous dose of 46.0Gy to mesorectum
      and draining lymph nodes, with a simultaneous-integrated-boost to the primary
      tumor up to a total dose of 55.2Gy. Planning objectives were 95% of prescribed
      dose to 95% of PTVs, while minimizing the volume of small bowel receiving more
      than 15Gy (V15) and the mean bladder dose. Dose gradient towards simultaneous
      integrated-boost (GI), calculated by dividing the volume receiving more then
      52.4Gy (95% of PTV55.2Gy)to the volume of PTV55.2Gy, was kept below 1.5. Mean
      beam-on time and amount of MUs were also analyzed. RESULTS: PTV swere adequately
      covered by all plans. Significant advantage was found for Tomotherapy in sparing
      small bowel (V15 = 112.7cm(3)SD73.4cm(3)) compared to RapidArc
      (133.4cm(3)SD75.3cm(3)) and HybridArc (143.7cm(3)SD74.4cm(3)) (p < 0.01). The
      mean bladder dose was better with RapidArc (20.6GySD2.2Gy) compared to HybridArc
      (24.2Gy SD4.3Gy) and Tomotherapy (23.0GySD4.7Gy) (p < 0.01). The mean beam-on
      time was significantly lower (p < 0.01) for HybridArc (2.7min SD0.8) and RapidArc
      (2.5min SD0.5) compared to Tomotherapy (11.0min SD0.7). The total amount of MUs
      was significantly (p < 0.01) lower for RapidArc (547SD44)compared to HybridArc
      (949 SD153). CONCLUSIONS: HybridArc is a feasible solution for preoperative RT
      with a simultaneous-integrated-boost in rectal cancer patients. It achieved
      similar PTV coverage with significant lower beam-on time, but less efficient in
      sparing small bowel and bladder compared to Tomotherapy and RapidArc. The added
      value of HybridArc is that the treatment modality can be implemented on every
      LINAC equipped with Dynamic-Conform-Arc and IMRT treatment techniques, while
      maintaining the same QA-schemes.

PMID- 22849724
TI  - Identification of a germicidal compound against picornavirus in bamboo
      pyroligneous acid.
AB  - The germicidal activity of pyroligneous acid (PA) against a picornavirus,
      encephalomyocarditis virus (EMCV), was analyzed, and the component responsible
      for its disinfectant activity was identified. Bamboo PA (BPA) inactivated EMCV,
      but neutralization of BPA abolished this activity. Using liquid-liquid phase
      extraction and silica gel column chromatography, the hydrophobic active fraction
      of BPA was separated and its 12 major components were identified. The active
      fraction was reconstructed by mixing synthetic chemicals at the determined
      concentrations, and a subtraction series of one chemical from the complete
      mixture was prepared. An in vitro virus assay demonstrated that phenol was the
      sole germicidal component, and acetic acid augmented the phenol's inactivating
      activity resulting in >5-log decrease in EMCV infectivity. Considering the low
      environmental risk of PA, these findings suggest that BPA is a potentially useful
      agent for preventing viral epidemics in agricultural and human environments.

PMID- 22849725
TI  - Discovery of the first thumb pocket 1 NS5B polymerase inhibitor (BILB 1941) with
      demonstrated antiviral activity in patients chronically infected with genotype 1
      hepatitis C virus (HCV).
AB  - Combinations of direct acting antivirals (DAAs) that have the potential to
      suppress emergence of resistant virus and that can be used in interferon-sparing
      regimens represent a preferred option for the treatment of chronic HCV infection.
      We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV
      NS5B polymerase that inhibit replication in replicon systems. Herein, we report
      the late-stage optimization of indole-based inhibitors, which began with the
      identification of a metabolic liability common to many previously reported
      inhibitors in this series. By use of parallel synthesis techniques, a sparse
      matrix of inhibitors was generated that provided a collection of inhibitors
      satisfying potency criteria and displaying improved in vitro ADME profiles.
      "Cassette" screening for oral absorption in rat provided a short list of
      potential development candidates. Further evaluation led to the discovery of the
      first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral
      activity in patients chronically infected with genotype 1 HCV.

PMID- 22849726
TI  - Contribution of interferon gamma release assays testing to the diagnosis of
      latent tuberculosis infection in HIV-infected patients: a comparison of
      QuantiFERON-TB Gold In Tube, T-SPOT.TB and tuberculin skin test.
AB  - BACKGROUND: Diagnosis and treatment of latent tuberculosis infection (LTBI) is
      the most effective strategy to control tuberculosis (TB) among patients with HIV
      infection. The tuberculin skin test (TST) was the only available method to
      identify LTBI. The aim of the present work was to evaluate the usefulness of the
      interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In
      Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of
      HIV-infected patients. METHODS: A prospective study was carried out in
      consecutive patients cared for in a single institution in Spain from January 2009
      to October 2010. IGRAs and TST were performed simultaneously. TST induration >= 5
      mm was considered positive. RESULTS: QFG, T-SPOT.TB and TST were performed in 373
      subjects. Median CD4 cell count was 470/MUl with a median nadir of 150/MUl. TST,
      QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively.
      Among 277 patients with neither past or current TB nor previous treatment for
      LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%)
      cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses
      of LTBI. When the results of both IGRAs were added, the number of diagnoses
      increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval
      [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of
      diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%-16.9%]
      [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/MUl and prior
      stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG
      and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 - 9.9; and aOR:
      3.3; 95% CI, 1.3 - 8.3, respectively). CONCLUSIONS: IGRAs were more sensitive
      than TST for diagnosis of M. tuberculosis infection in HIV-infected patients.
      Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI
      screening in this population.

PMID- 22849729
TI  - Intersection of surgical pathology and molecular diagnostics for targeted
      therapy: recommendation for synoptic reporting.

PMID- 22849727
TI  - Assessment of service quality of public antiretroviral treatment (ART) clinics in
      South Africa: a cross-sectional study.
AB  - BACKGROUND: In South Africa the ever increasing demand for antiretroviral
      treatment (ART) runs the risk of leading to sub-optimal care in public sector ART
      clinics that are overburdened and under resourced. This study assessed the
      quality of ART services to identify service areas that require improvement.
      METHODS: A cross-sectional study was carried out at 16 of 17 public ART clinics
      in the target area in greater Pretoria, South Africa. Trained participant
      observers presented as ART qualifying HIV positive patients that required a visit
      to assess treatment readiness. They evaluated each facility on five different
      occasions between June and November 2009, assessing the time it took to get an
      appointment, the services available and accessed, service quality and the
      duration of the visit. Services (reception area, clinician's consultation, HIV
      counselling, pharmacy, nutrition counselling and social worker's assessment) were
      assessed against performance standards that apply to all clinics. Service quality
      was expressed as scores for clinic performance (CPS) and service performance
      (SPS), defined as the percentage of performance standards met per clinic and
      service area. RESULTS: In most of the clinics (62.5%) participant observers were
      able to obtain an appointment within one week, although on the day of their visit
      essential services could not always be accessed. The median CPS of the assessed
      facilities was 68.5 with four clinics not meeting minimum standards (CPS > 60).
      The service areas that performed least well were the clinician's consultation
      (SPS 67.3) and HIV counselling (SPS 70.7). Most notably, clinicians performed a
      physical examination in only 41.1% of the visits and rarely did a complete TB
      symptom screening. Counsellors frequently failed to address prevention of HIV
      transmission. CONCLUSIONS: Overall public sector ART clinics in greater Pretoria
      were easily accessible and their services were of an acceptable quality. However,
      the time spent at the clinic to complete the services was found to be very long
      and there was considerable variation in adherence to performance standards within
      the services, particularly in respect of clinician's consultation and
      counselling. Clinic management needs to ensure efficient clinic organisation and
      to improve adherence to performance standards in key service areas.

PMID- 22849730
TI  - Life-long learning and self-assessment.
AB  - New Frontiers in Pathology is a unique educational event intended to meet the
      ongoing educational needs of practicing pathologists. Continuous medical
      education (CME) is required for maintenance of licensure by virtually all state
      licensing bodies. Satisfying CME requirements hinges on earning a minimum number
      of American Medical Association Physician Recognition Award category 1 credits
      through various activities, including courses like New Frontiers in Pathology
      that are accredited by the Accreditation Council for Continuing Medical
      Education. Self-assessment modules (SAMs) are a key component of the American
      Board of Pathology expectations for maintenance of board certification. Beginning
      in 2006, the American Board of Pathology granted only time-limited certificates
      as part of an American Board of Medical Specialties-wide process for maintenance
      of board certification. Maintenance of board certification has requirements in 4
      categories: professional standing, life-long learning and self-assessment,
      cognitive expertise, and evaluation of performance in practice. Life-long
      learning and self-assessment includes not only the traditional elements of CME
      but also the SAMs that are defined as educational products comprising self
      administered examinations with a predetermined minimum performance level and a
      mechanism for receiving feedback. New Frontiers in Pathology will offer SAMs, in
      addition to the American Medical Association Physician Recognition Award category
      1 credits, which it has been accredited to do since its inception, at its 2012
      conference scheduled for August 3 through August 5 at The Homestead Resort,
      Michigan's largest waterfront resort on beautiful Lake Michigan.

PMID- 22849731
TI  - The differential diagnosis of colitis in endoscopic biopsy specimens: a review
      article.
AB  - CONTEXT: A variety of inflammatory disorders may affect the colon, with widely
      differing clinical outcomes and management. These conditions encompass a spectrum
      of acute and chronic conditions. OBJECTIVE: Review the pathology of the major
      colitides and highlight the most diagnostically useful features. DATA SOURCES:
      Review of recent literature supplemented with personal experience in the field of
      gastrointestinal pathology. CONCLUSIONS: The etiologies associated with the
      various types of colitis are diverse and the range of histologic changes is
      somewhat limited. Nevertheless, the combination of clinical and endoscopic data
      coupled with histopathology allows for accurate classification in the majority of
      cases.

PMID- 22849732
TI  - Gastrointestinal lymphomas: entities and mimics.
AB  - The gastrointestinal tract is the most common extranodal site of lymphoma
      involvement. Although B-cell lymphomas are by far the most frequent type found in
      this location, gastrointestinal lymphomas are a diverse group of neoplasms, many
      of which are characterized by distinctive clinicopathologic settings. Diffuse
      large B-cell lymphoma and marginal-zone lymphoma of mucosa-associated lymphoid
      tissue are commonly encountered, but other less-common entities can pose
      diagnostic challenges, mimicking both benign, reactive conditions and each other.
      We describe several different lymphoma subtypes, with a focus on frequently
      encountered challenges in differential diagnosis.

PMID- 22849733
TI  - Transformation of indolent mantle cell lymphoma to pleomorphic mantle cell
      lymphoma: case report and review of clinical and morphologic variants.
AB  - We report a case of indolent mantle cell lymphoma with progression to pleomorphic
      mantle cell lymphoma 8 years after initial presentation. The first lymph node
      biopsy showed expanded mantle zones composed of uniformly small B lymphocytes. A
      cyclin D1 immunohistochemical stain was negative and the patient was observed.
      Eight years later, the patient developed symptomatic splenomegaly. Microscopic
      examination of the spleen revealed expanded mantle zones with an increased number
      of large cells with irregular nuclear contours. Immunohistochemistry for cyclin
      D1 was positive. A repeat cyclin D1 immunohistochemical staining performed on the
      initial lymph node biopsy was positive, indicating an inadequate initial study.
      Immunoglobulin heavy-chain gene rearrangement studies confirmed clonal identity.
      A revised diagnosis of indolent mantle cell lymphoma with progression to
      pleomorphic mantle cell lymphoma was rendered. The differential diagnosis of
      mantle cell lymphoma, including clinical and morphologic variants, is discussed.

PMID- 22849734
TI  - Primary cutaneous diffuse large B-cell lymphoma, leg type: diagnostic
      considerations.
AB  - CONTEXT: Primary cutaneous diffuse large B-cell lymphoma, leg type, may show
      features that overlap with other lymphomas. However, timely recognition of this
      entity can have important clinical and therapeutic implications. OBJECTIVE: To
      review the clinical, morphologic, and immunophenotypic characteristics of primary
      cutaneous diffuse large B-cell lymphoma, leg type, and juxtapose these features
      with other diagnostic considerations. In particular, other variants of primary
      cutaneous diffuse large B-cell lymphoma, as well as primary cutaneous follicle
      center lymphoma, will be reviewed. Additionally, systemic/extracutaneous
      lymphomas will be discussed, including diffuse large B-cell lymphoma, not
      otherwise specified, Epstein-Barr virus-positive diffuse large B-cell lymphoma of
      the elderly, and lymphomatoid granulomatosis. DATA SOURCES: Relevant literature
      will be reviewed and key differentiating findings will be highlighted.
      CONCLUSIONS: Although primary cutaneous diffuse large B-cell lymphoma, leg type,
      may show aspects that overlap with other lymphomas, it can be distinguished from
      other entities in the differential diagnosis.

PMID- 22849735
TI  - Diffuse malignant mesothelioma.
AB  - Diffuse malignant mesothelioma (DMM) is an uncommon cancer with great clinical
      significance because it currently remains an incurable disease, and most patients
      die within months after diagnosis. Although DMM incidence is leveling off or
      decreasing in developed countries because of the strict control of asbestos use,
      it is increasing in countries without adequate asbestos control. In some
      settings, benign, reactive mesothelial hyperplasias and organizing pleuritis can
      be difficult to differentiate from DMM and vice versa, and the variety of DMM's
      histopathologic features generates an extensive list of differential diagnoses
      with other malignancies, particularly, metastatic malignancies, which are more
      frequent in the pleura than are primary malignancies. These two issues are the
      topic of discussion in this review, along with a brief presentation of a case of
      DMM that presented in a 66-year-old man with recurrent, right pleural effusions,
      and in whom, diagnosis of DMM had not been suspected clinically,
      radiographically, surgically, grossly, or initially, on frozen section. It was
      not until focal invasion into the skeletal muscle was discovered on permanent
      sections that a diagnosis of DMM could be established.

PMID- 22849736
TI  - Hypersensitivity pneumonia: role of surgical lung biopsy.
AB  - Lung biopsy often plays a key role in identifying patients with hypersensitivity
      pneumonia, especially in the absence of a typical history. A 69-year-old woman
      with a 2-year history of unexplained dyspnea on exertion underwent surgical lung
      biopsy for diagnosis of diffuse lung disease thought to represent idiopathic
      pulmonary fibrosis. Her biopsy showed honeycomb change and fibroblast foci
      suggestive of usual interstitial pneumonia, but also showed areas of cellular
      interstitial pneumonia with chronic bronchiolitis and a pattern of granulomatous
      inflammation typical of hypersensitivity pneumonia. The classic features of
      hypersensitivity pneumonia in surgical lung biopsy are emphasized, including a
      bronchiolocentric cellular interstitial pneumonia, chronic bronchiolitis, and
      poorly formed nonnecrotizing granulomas. As illustrated in our patient, sometimes
      subtle histologic clues are key in separating hypersensitivity pneumonia from
      usual interstitial pneumonia and other forms of idiopathic interstitial
      pneumonia. Making the distinction is important given differences in treatment
      strategies and natural history.

PMID- 22849737
TI  - Metaplastic carcinomas of the breast: diagnostic challenges and new translational
      insights.
AB  - Comprising less than 1% of invasive carcinomas of the breast, metaplastic
      carcinomas are a heterogeneous group of malignant tumors in which part or all of
      the carcinomatous epithelium is transformed into a nonglandular (metaplastic)
      growth process. Metaplastic carcinomas with a low-grade spindle cell component
      resembling fibromatosis, as in our present case, are worthy of particular note
      because they are infrequent, difficult to recognize, and have a high risk of
      local recurrence. The differential diagnosis of metaplastic carcinomas depends on
      the degree of atypia observed in the tumor and includes exuberant scars,
      fibromatosis, nodular fasciitis, myofibroblastomas, pseudoangiomatous stromal
      hyperplasia, acute and chronic abscess with fat necrosis, malignant phyllodes
      tumor, and primary or metastatic sarcoma. Limited studies done on the molecular
      pathology of metaplastic carcinomas show that activation of the Wnt signaling
      pathway is common in these tumors and that approximately 70% of metaplastic
      carcinomas show EGFR gene amplification and overexpression. This may have
      treatment implications because they may lead to targeted treatment for patients
      with metaplastic carcinomas.

PMID- 22849738
TI  - Tenosynovial giant cell tumor: case report and review.
AB  - Tenosynovial giant cell tumors are a group of generally benign intra-articular
      and soft tissue tumors with common histologic features. They can be roughly
      divided into localized and diffuse types. Localized types include giant cell
      tumors of tendon sheath and localized pigmented villonodular synovitis, whereas
      diffuse types encompass conventional pigmented villonodular synovitis and diffuse
      type giant cell tumor. Localized tumors are generally indolent, whereas diffuse
      tumors are locally aggressive. Recent developments indicate that tenosynovial
      giant cell tumors are clonal neoplastic tumors driven by overexpression of CSF1.
      Herein, I report a case of intra-articular, localized tenosynovial giant cell
      tumor (or localized pigmented villonodular synovitis) and review the
      classification, histopathology, and recent developments regarding its
      pathogenesis.

PMID- 22849739
TI  - High-grade carcinomas involving the renal sinus: report of a case and review of
      the differential diagnosis and immunohistochemical expression.
AB  - We report the case of a high-grade carcinoma involving the kidney in a young male
      with renal vein thrombosis and review the differential diagnosis and
      immunohistochemical workup. High-grade neoplasms involving the renal sinus
      include collecting duct carcinomas (CDCs), renal medullary carcinomas (RMCs),
      invasive high-grade urothelial carcinoma (UC) of the upper urinary tract, clear
      cell renal cell carcinoma, and type 2 papillary renal cell carcinoma.
      Distinguishing UC from CDC and RMC is problematic in small biopsy samples. The
      diagnosis of CDC (a rare, aggressive subtype of renal cell carcinoma) is
      challenging and requires the exclusion of UC. Renal medullary carcinoma is
      characterized by an appropriate clinical setting and consistent loss of nuclear
      expression of integrase interactor 1 (INI-1). A panel consisting of p63, paired
      box gene 8 (PAX8), and INI-1 is most optimal in distinguishing UC from CDC and
      RMC. A subset of urothelial carcinoma of upper urinary tract may be positive with
      PAX8.

PMID- 22849740
TI  - Teratoid hepatoblastoma with abundant neuroendocrine and squamous differentiation
      with extensive parenchymal metastasis.
AB  - Teratoid hepatoblastoma is a rare histologic subtype accounting for 4% to 10% of
      all hepatoblastomas and is characterized by the presence of divergent
      differentiation, including squamous, mucinous, melanocytic, cartilaginous,
      osseous, skeletal muscle, and neural elements. It is postulated that the teratoid
      elements might derive from multipotential less-differentiated stem cells.
      Teratoid hepatoblastoma responds poorly to chemotherapy and therefore recognition
      of this variant has prognostic implications. We describe a 11/2-year-old child
      with teratoid hepatoblastoma characterized by unusual clinical and morphologic
      patterns including prominent neuroendocrine and squamous differentiation.

PMID- 22849741
TI  - Clear cell tumors of the central nervous system: a case-based review.
AB  - Clear cell tumors of the central nervous system (CNS) encompass a variety of
      tumor subtypes that are challenging to diagnose given their similar morphologic
      features. Here, I use a case-based approach to review the clinicopathologic and
      radiologic features to help guide the general pathologist in the diagnosis of
      clear cell tumors of the CNS. First, the reader is invited to study 6 images of
      different CNS tumors with clear cell morphology. Then, each case is expanded in
      light of clinical and radiologic data and includes a histopathologic description
      of the tumor. A brief discussion follows with up-to-date diagnostic tools.
      Finally, I propose an immunohistochemical algorithm to navigate through the
      complex features that characterize clear cell tumors of the CNS. This review aims
      to provide a comprehensive approach to diagnosing clear cell neoplasms of the CNS
      based on improved assessment of the clinicopathologic and radiologic features of
      each entity.

PMID- 22849742
TI  - External and internal influences on muscle pathology.
AB  - Three cases of different types of neuromuscular diseases demonstrate different
      muscle responses to external stress or intrinsic muscle abnormalities. The first
      muscle biopsy shows stenosis of its vessels causing acute muscle ischemia, stress
      from an external vascular disease. The muscle response is similar to the cellular
      necrosis seen in primary muscle diseases (myopathies), but the histologic pattern
      is more focal than most myopathies. The second muscle biopsy demonstrates the
      effects of external motor nerve injury or disease causing groups of muscle fibers
      to atrophy. If a nerve reinnervates the muscle, it changes the fiber types in
      distinct patterns. The third muscle biopsy shows an intrinsic muscle abnormality
      causes chronic failure of the muscle fibers to thrive and repeated attempts by
      the fibers to regenerate, stimulating other tissue repair processes, like
      fibrosis, to change the muscle. Depending on the etiologic factor, muscle will
      respond to internal and external influences in different manners.

PMID- 22849744
TI  - Differentiation of malignant melanoma from benign nevus using a novel genomic
      microarray with low specimen requirements.
AB  - CONTEXT: Histologic examination of clinically suspicious melanocytic lesions is
      very sensitive and specific for the detection of malignant melanoma. Yet, the
      malignant potential of a small percentage of melanocytic lesions remains
      histologically uncertain. Molecular testing offers the potential to detect the
      genetic alterations that lead to malignant behavior without overt histologic
      evidence of malignancy. OBJECTIVE: To differentiate benign melanocytic nevi from
      malignant melanoma and to predict the clinical course of melanocytic lesions with
      ambiguous histology using a novel genomic microarray. DESIGN: We applied a newly
      developed single-nucleotide polymorphism genomic microarray to formalin-fixed,
      paraffin-embedded melanocytic lesions to differentiate benign nevi (n  =  23)
      from malignant melanoma (n  =  30) and to predict the clinical course of a set of
      histologically ambiguous melanocytic lesions (n  =  11). RESULTS: For cases with
      unambiguous histology, there was excellent sensitivity and specificity for
      identifying malignant melanoma with this genomic microarray (89% sensitivity,
      100% specificity). For cases with ambiguous histology, the performance of this
      genomic microarray was less impressive. CONCLUSIONS: Without microdissection and
      with quantities of DNA one-tenth what is required for more commonly used
      microarrays, this microarray can differentiate between malignant melanoma and
      benign melanocytic nevi. For histologically ambiguous lesions, longer clinical
      follow-up is needed to confidently determine the sensitivity and specificity of
      this microarray. Some of the previous technical hurdles to the clinical
      application of genomic microarray technology are being overcome, and the
      advantages over targeted fluorescence in situ hybridization assays currently in
      clinical use are becoming apparent.

PMID- 22849743
TI  - Antibody-based detection of ERG rearrangements in prostate core biopsies,
      including diagnostically challenging cases: ERG staining in prostate core
      biopsies.
AB  - CONTEXT: Fusions of androgen-regulated genes and v-ets erythroblastosis virus E26
      oncogene homolog (avian) (ERG) occur in approximately 50% of prostate cancers,
      encoding a truncated ERG product. In prostatectomy specimens, ERG rearrangements
      are greater than 99% specific for prostate cancer or high-grade prostatic
      intraepithelial neoplasia adjacent to ERG-rearranged prostate cancer by
      fluorescence in situ hybridization and immunohistochemistry. OBJECTIVE: To
      evaluate ERG staining by immunohistochemistry on needle biopsies, including
      diagnostically challenging cases. DESIGN: Biopsies from a retrospective cohort (n
      =  111) enriched in cores requiring diagnostic immunohistochemistry and a
      prospective cohort from all cases during 3 months (n  =  311) were stained with
      an anti-ERG antibody (clone EPR3864). RESULTS: Among evaluable cores (n  =  418),
      ERG staining was confined to cancerous epithelium (71 of 160 cores; 44%), high
      grade prostatic intraepithelial neoplasia (12 of 68 cores; 18%), and atypical
      foci (3 of 28 cores; 11%), with staining in only 2 of 162 cores (1%) diagnosed as
      benign. The ERG was expressed in about 5 morphologically benign glands across 418
      cores and was uniformly expressed by all cancerous glands in 70 of 71 cores
      (99%). CONCLUSIONS: ERG staining is more prostate cancer-specific than alpha
      methylacyl-coenzyme A racemase, and staining in an atypical focus supports a
      diagnosis of cancer if high-grade prostatic intraepithelial neoplasia can be
      excluded. Thus, ERG staining shows utility in diagnostically challenging biopsies
      and may be useful in molecularly subtyping prostate cancer and in stratifying
      isolated high-grade prostatic intraepithelial neoplasia by risk of subsequent
      cancer.

PMID- 22849745
TI  - Intracellular human papillomavirus E6, E7 mRNA quantification predicts CIN 2+ in
      cervical biopsies better than Papanicolaou screening for women regardless of age.
AB  - CONTEXT: Cervical cancer screening in women younger than 30 years relies on
      cervical cytology because of the poor performance of human papillomavirus (HPV)
      DNA testing in this age group. OBJECTIVES: To determine the performance of in
      cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high
      grade cervical intraepithelial neoplasia in women younger than 30 years. DESIGN:
      We analyzed 3133 cytology specimens from a screening population of women aged 19
      75 years investigate HPV OncoTect as a triage/secondary screening test for
      atypical squamous cells of undetermined significance (ASCUS) and low-grade
      squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years.
      Test results were compared to histology in 246 cases. RESULTS: The sensitivity of
      E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and
      older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+
      lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology
      (>=ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women
      30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+
      in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and
      CIN 3+ in both groups of women compared to a specificity of abnormal cytology of
      <10% for CIN 2+ and CIN 3+ in both groups. CONCLUSIONS: HPV OncoTect demonstrates
      a performance that would be effective for ASCUS/LSIL triage in women including
      those younger than 30 years.

PMID- 22849746
TI  - Gastroblastoma in a 28-year-old man with nodal metastasis: proof of the malignant
      potential.
AB  - Gastroblastoma is a newly defined neoplasm of children and young adults with only
      4 reported cases to date. Morphologically, the tumor is a mixture of epithelial
      structures and stromal elements with minimal cytologic atypia. In these 4
      reported cases, there were no metastases or postresection recurrences. We report
      a case of gastroblastoma in a 28-year-old man with a histologic nodal metastasis
      and clinical distant metastases.

PMID- 22849747
TI  - Cerebellar liponeurocytoma.
AB  - Cerebellar liponeurocytoma is a rare neoplasm with distinctive morphologic
      features. It typically involves the cerebellar hemispheres of middle-aged to
      older adults. The tumor is composed of a uniform population of neurocytic cells
      possessing round to oval nuclei and pale to clear cytoplasm. A variable degree of
      lipidization of the tumor cells is present, lending a resemblance to mature
      adipose tissue. Immunohistochemistry serves to confirm the neurocytic
      differentiation of the tumor cells. In the 2007 revision of the World Health
      Organization classification of central nervous system tumors, cerebellar
      liponeurocytoma was reclassified as a grade II neoplasm to reflect a higher
      recurrence rate than was previously appreciated.

PMID- 22849748
TI  - Sex differences in alcohol misuse and estimated blood alcohol concentrations
      among emergency department patients: implications for brief interventions.
AB  - OBJECTIVES: The objective was to assess the relationship between alcohol use and
      misuse and patient sex among emergency department (ED) patients by comparing self
      reported estimates of quantity and frequency of alcohol use, estimated blood
      alcohol concentrations (eBACs) when typically drinking and during heavy episodic
      drinking (binging), and alcohol misuse severity, to understand sex differences in
      alcohol use and misuse for this population. METHODS: The authors surveyed a
      random sample of nonintoxicated, subcritically ill or injured, 18- to 64-year-old
      English- or Spanish-speaking patients on randomly selected dates and times at two
      EDs during July 2009 and August 2009. Participants self-administered a
      questionnaire about their self-reported alcohol use during a typical month within
      the past 12 months and the Alcohol Use Disorders Identification Test (AUDIT).
      Using the formulae by Matthews and Miller, sex-specific eBACs were calculated for
      participants according to their reported weight and the number of reported
      alcoholic drinks consumed on days when typically drinking and on days of heavy
      episodic (binge) drinking (five or more drinks/occasion for men, four or more
      drinks for women). Sex-specific alcohol misuse severity levels (low-risk,
      harmful, hazardous, and dependence) were calculated using AUDIT scores. Wilcoxon
      rank-sum and Pearson's chi-square tests were used to compare outcomes by sex.
      Negative binomial regression was used to assess the relationship between sex and
      the number of drinks consumed on a typical day, the number of days spent drinking
      and binging, and estimated AUDIT scores. Logistic regression was used to assess
      the outcome of the presence of binging according to sex. Multinomial logistic
      regression was used to compare by sex the percentage of days spent drinking and
      binging in 1 month, eBACs when typically drinking and when binging, and AUDIT at
      risk drinking levels. Incidence rate ratios (IRRs) and adjusted odds ratios
      (AORs) with 95% confidence intervals (CIs) were estimated. All models were
      adjusted for patient demographic characteristics. RESULTS: Of the 513
      participants, 52.1% were women, 55.8% were white non-Hispanic, and their median
      age was 34 years (interquartile range [IQR] = 25 to 46 years). Men reported
      greater mean alcohol consumption than women when typically drinking (4.3 vs. 3.3
      drinks/day; p < 0.001) and during heavy episodic drinking (8.6 vs. 5.3
      drinks/occasion; p < 0.001). Men spent more days drinking (IRR = 1.41, 95% CI =
      1.19 to 1.65) and engaging in heavy episodic drinking (IRR = 1.68, 95% CI = 1.31
      to 2.17) than women. Additionally, men were more likely to engage in heavy
      episodic drinking (AOR = 1.72, 95% CI = 1.16 to 2.56) than women. However, the
      mean eBACs for men and women were similar when typically drinking (0.05 vs. 0.06;
      p < 0.13) and during heavy episodic drinking (0.13 vs. 0.12; p < 0.13). Mean
      AUDIT scores were greater for men than women (7.5 vs. 5.3; p < 0.001), although
      alcohol misuse severity levels were similar between men and women (24.4% vs.
      26.6% for hazardous, 2.8% vs. 2.2% for harmful, and 6.5% vs. 3.4% for dependence;
      p < 0.38). CONCLUSIONS: Although men drink more than women, women have similar
      eBACs with comparable levels of alcohol misuse. Women may benefit from
      recognizing that they are reaching similar levels of intoxication compared to
      men. Addressing these differences and possible health implications in future ED
      brief interventions may induce changes in problematic alcohol use among women.

PMID- 22849749
TI  - Linkage analysis confirms heterogeneity of hereditary gingival fibromatosis.
AB  - OBJECTIVES: Hereditary Gingival Fibromatosis (HGF) is a rare benign fibrous
      lesion of the gingival tissues presumably caused by single gene defects. The aim
      of this study was to identify the genetic defect leading to HGF in an extended
      pedigree. MATERIALS AND METHODS: We report the clinical features and genetic
      analysis of a family affected by HGF. A total of 17 subjects were assessed
      clinically and had blood samples taken for DNA extraction. Multipoint parametric
      linkage analysis was performed to identify the possible chromosomal location
      responsible for HGF in this family. RESULTS: Presence of severe HGF associated
      with tooth impaction was confirmed for seven members of this three-generation
      family. Linkage analysis revealed that loci on chromosomes 7, 10, 13, 15, 16, 17,
      19 and 20 were linked to this trait. Previously found mutations in the SOS1 and
      GINGF loci were therefore excluded by this analysis. CONCLUSIONS: This study
      brings further evidence for genetic heterogeneity of HGF and points towards the
      existence of different, not-yet-identified genes linked to this condition.

PMID- 22849752
TI  - Tracing the sources of the different magnetic behavior in the two phases of the
      bistable (BDTA)2[Co(mnt)2] compound.
AB  - A complete computational study of the magnetic properties of the two known phases
      of the bistable (BDTA)(2)[Co(mnt)(2)] compound is presented. The origin of their
      different magnetic properties can be traced to a variation in the values of the g
      tensor, together with a hitherto unknown change in the J(AB) values and their
      magnetic topology.

PMID- 22849753
TI  - Parathyroid hormone is associated with biomarkers of insulin resistance and
      inflammation, independent of vitamin D status, in obese adolescents.
AB  - BACKGROUND: 25-Hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) have been
      shown to correlate with several markers of metabolic syndrome in adult
      populations. We evaluated the relationship between circulating intact parathyroid
      hormone (iPTH) and 25(OH)D and indices of metabolic syndrome in obese
      adolescents. METHODS: Body mass index (BMI), body composition, 25(OH)D, iPTH,
      fasting lipids, glucose, high-sensitivity C-reactive protein (hsCRP),
      glycosylated hemoglobin (HbA1c), insulin, and the homeostatic model assessment
      for insulin resistance (HOMA-IR) were evaluated in 133 obese adolescents.
      RESULTS: Vitamin D deficiency [25(OH)D <50 nmol/L] was present in 45.1% of all
      patients, with higher prevalence in African-American (AA) and Hispanic (H) than
      Caucasian (C) subgroups (63.9% and 56.4% vs. 25.9%; P<0.001). iPTH and 25(OH)D
      were inversely correlated (r=-0.75; P<0.0001), with AA displaying a higher iPTH:
      25(OH)D ratio than H and C subgroups (P<0.05). Whereas fat mass (FM) was
      negatively correlated with 25(OH)D (r=-0.30; p<0.001), it was positively
      correlated with iPTH levels (r=0.38; P<0.0001). Metabolic syndrome was identified
      in 57.9% of the cohort with higher iPTH, iPTH:25(OH)D ratio, but lower 25(OH)D
      than participants without metabolic syndrome (P<0.02). Whereas iPTH showed main
      effects for hsCRP (beta=0.24, t=2.61, P<0.05) and triglycerides:high-density
      lipoprotein cholesterol (TG:HDL-C) (beta=0.21, t=2.13, p<0.05), independent of
      serum 25(OH)D, it did not reveal a main effect for HOMA-IR. CONCLUSIONS:
      Metabolic syndrome is associated with a higher iPTH:25(OH)D ratio than those
      without metabolic syndrome, implying greater risk of cardiovascular morbidities
      among AA subjects than other ethnic groups. Furthermore, the serum iPTH level is
      a predictor of chronic inflammation and dyslipidemia, independent of 25(OH)D.

PMID- 22849751
TI  - Autism genetics: searching for specificity and convergence.
AB  - Advances in genetics and genomics have improved our understanding of autism
      spectrum disorders. As many genes have been implicated, we look to points of
      convergence among these genes across biological systems to better understand and
      treat these disorders. 

PMID- 22849755
TI  - Medial arcuate ligament: a new anatomic landmark facilitates the location of the
      renal artery in retroperitoneal laparoscopic renal surgery.
AB  - PURPOSE: The purpose of this study was to introduce a new method for locating the
      renal artery during retroperitoneal laparoscopic renal surgery. PATIENTS AND
      METHODS: The medial arcuate ligament (MAL) is a tendinous arch in the fascia
      under the diaphragm that arches across the psoas major muscle and is attached
      medially to the side of the first or the second lumbar vertebra. The renal artery
      arises at the level of the intervertebral disc between the L1 and L2 vertebrae.
      We evaluate the role of the MAL that serves as an anatomic landmark for locating
      the renal artery during retroperitoneal laparoscopic renal surgery. RESULTS:
      There is a reproducible consistent anatomic relationship between MAL and the
      renal artery in 210 cases of retroperitoneal laparoscopic renal surgery. Two main
      types of the MAL, the "narrow arch" and the "fascial band" types, can be
      observed. CONCLUSION: MAL can serve as an accurate and reproducible anatomic
      landmark for the identification of the renal artery during retroperitoneal
      laparoscopic renal surgery.

PMID- 22849754
TI  - Effect of survey instrument on participation in a follow-up study: a
      randomization study of a mailed questionnaire versus a computer-assisted
      telephone interview.
AB  - BACKGROUND: Many epidemiological and public health surveys report increasing
      difficulty obtaining high participation rates. We conducted a pilot follow-up
      study to determine whether a mailed or telephone survey would better facilitate
      data collection in a subset of respondents to an earlier telephone survey
      conducted as part of the National Birth Defects Prevention Study. METHODS: We
      randomly assigned 392 eligible mothers to receive a self-administered, mailed
      questionnaire (MQ) or a computer-assisted telephone interview (CATI) using
      similar recruitment protocols. If mothers gave permission to contact the fathers,
      fathers were recruited to complete the same instrument (MQ or CATI) as mothers.
      RESULTS: Mothers contacted for the MQ, within all demographic strata examined,
      were more likely to participate than those contacted for the CATI (86.6% vs.
      70.6%). The median response time for mothers completing the MQ was 17 days,
      compared to 29 days for mothers completing the CATI. Mothers completing the MQ
      also required fewer reminder calls or letters to finish participation versus
      those assigned to the CATI (median 3 versus 6), though they were less likely to
      give permission to contact the father (75.0% vs. 85.8%). Fathers contacted for
      the MQ, however, had higher participation compared to fathers contacted for the
      CATI (85.2% vs. 54.5%). Fathers recruited to the MQ also had a shorter response
      time (median 17 days) and required fewer reminder calls and letters (median 3
      reminders) than those completing the CATI (medians 28 days and 6 reminders).
      CONCLUSIONS: We concluded that offering a MQ substantially improved participation
      rates and reduced recruitment effort compared to a CATI in this study. While a
      CATI has the advantage of being able to clarify answers to complex questions or
      eligibility requirements, our experience suggests that a MQ might be a good
      survey option for some studies.

PMID- 22849756
TI  - Synthesis, characterization, and magnetic properties of monodisperse CeO2
      nanospheres prepared by PVP-assisted hydrothermal method.
AB  - Ferromagnetism was observed at room temperature in monodisperse CeO2 nanospheres
      synthesized by hydrothermal treatment of Ce(NO3)3.6H2O using polyvinylpyrrolidone
      as a surfactant. The structure and morphology of the products were characterized
      by X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy,
      high-resolution transmission electron microscopy, and field-emission scanning
      electron microscopy (FE-SEM). The optical properties of the nanospheres were
      determined using UV and visible spectroscopy and photoluminescence (PL). The
      valence states of Ce ions were also determined using X-ray absorption near edge
      spectroscopy. The XRD results indicated that the synthesized samples had a cubic
      structure with a crystallite size in the range of approximately 9 to 19 nm. FE
      SEM micrographs showed that the samples had a spherical morphology with a
      particle size in the range of approximately 100 to 250 nm. The samples also
      showed a strong UV absorption and room temperature PL. The emission might be due
      to charge transfer transitions from the 4f band to the valence band of the oxide.
      The magnetic properties of the samples were studied using a vibrating sample
      magnetometer. The samples exhibited room temperature ferromagnetism with a small
      magnetization of approximately 0.0026 to 0.016 emu/g at 10 kOe. Our results
      indicate that oxygen vacancies could be involved in the ferromagnetic exchange,
      and the possible mechanism of formation was discussed based on the experimental
      results.

PMID- 22849757
TI  - Firefighter's personal protective equipment and the chronotropic index.
AB  - The purpose of this study was to investigate the effects of personal protective
      equipment (PPE) on cardiovascular and metabolic responses during incremental
      exercise, and to determine if PPE affects the relationship between heart rate
      (HR) and oxygen uptake when expressed as the chronotropic index (CI). Ten male
      participants performed graded exercise tests under three conditions: control
      (CON), (PPE) and weighted vest (WV) (same weight as PPE). Time to exhaustion was
      significantly longer in the CON compared to the other conditions (p < 0.01).
      Submaximal oxygen uptake and HR were significantly lower in the CON compared to
      the PPE and WV conditions. The CI (CON, 32.2 +/- 4.5; PPE, 31.7 +/- 5.7; WV, 32.6
      +/- 4.9) was similar in all three conditions. This study has shown that
      additional weight and encapsulating clothing leads to elevations in HR and oxygen
      uptake compared to a control condition, however, the CI remains unaffected.
      PRACTITIONER SUMMARY: Firefighters wear personal protective equipment that is
      designed to protect the wearer; however it also imposes a physiological burden.
      It is known that work in firefighting PPE increases cardiovascular and metabolic
      strain. This study has shown that PPE does not alter the relationship between
      heart rate and oxygen uptake.

PMID- 22849758
TI  - Progesterone for hot flush and night sweat treatment--effectiveness for severe
      vasomotor symptoms and lack of withdrawal rebound.
AB  - A controlled trial recently showed that oral micronized progesterone
      (Progesterone, 300 mg at h.s. daily) was effective for vasomotor symptoms (VMS)
      in 133 healthy early postmenopausal women. Here, we present subgroup data in
      women with severe VMS (50 VMS of moderate-severe intensity/wk) and also 1-mo
      withdrawal study outcomes. Women with severe VMS (n = 46) resembled the full
      cohort but experienced 10 VMS/d of 3 of 4 intensity. On therapy, the progesterone
      VMS number (#) decreased significantly more than placebo # to 5.5/day (d) versus
      8/d (ANCOVA -2.0 95% CI: -3.5 to -0.4). Just after trial mid-point, a withdrawal
      substudy (D/C) was added--56 women were invited and 34 (61%) took part
      (progesterone 17; placebo 17). Those in the D/C cohort resembled the whole
      cohort. On stopping, VMS gradually increased--at D/C week 4, on progesterone, VMS
      daily # reached 78% and significantly less than baseline (-3.0 to -0.8) but
      placebo VMS # did not differ from run-in. In summary, progesterone is effective
      for severe VMS and does not cause a rebound increase in VMS when stopped. That
      progesterone may be used alone for severe VMS and unlike estrogen does not appear
      to cause a withdrawal rebound increases VMS treatment options.

PMID- 22849759
TI  - Investigation and management of hepatic incidentalomas.
AB  - With the widespread use of medical imaging has come the detection of incidental
      liver lesions that are, by and large, asymptomatic prior to their discovery.
      These lesions may become a source of anxiety and often require further
      investigation to reassure the patient of their usually benign nature. Use of
      contemporary hepatobiliary imaging and simple laboratory tests often allow a
      definite diagnosis to be made without resorting to exhaustive investigation or
      inappropriate surgery. The goal of this paper is to review the clinical features
      and imaging characteristics of common and important liver incidentalomas, their
      natural course, complications, and indications for surgical or other
      intervention.

PMID- 22849761
TI  - Nickel-catalyzed diastereoselective alkyl-alkyl Kumada coupling reactions.
AB  - A nickel pincer complex is found to catalyze alkyl-alkyl Kumada coupling
      reactions of 1,3- and 1,4-substituted cyclohexyl halides and tetrahydropyrans
      with an excellent diastereoselectivity. The mechanistic investigation of the
      coupling reactions provides evidence that the activation of alkyl halides is
      reversible.

PMID- 22849760
TI  - Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is recognized as the most potent microbial
      mediator presaging the threat of invasion of Gram-negative bacteria that
      implicated in the pathogenesis of sepsis and septic shock. This study was
      designed to examine the microRNA (miRNA) expression in whole blood from mice
      injected with intraperitoneal LPS. METHODS: C57BL/6 mice received intraperitoneal
      injections of varying concentrations (range, 10-1000 MUg) of LPS from different
      bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas
      aeruginosa, Salmonella enterica, and Serratia marcescens and were killed 2, 6,
      24, and 72 h after LPS injection. Whole blood samples were obtained and tissues,
      including lung, brain, liver, and spleen, were harvested for miRNA expression
      analysis using an miRNA array (Phalanx miRNA OneArray(r) 1.0). Upregulated
      expression of miRNA targets in the whole blood of C57BL/6 and Tlr4(-/-) mice
      injected with LPS was quantified using real-time RT-PCR and compared with that in
      the whole blood of C57BL/6 mice injected with lipoteichoic acid (LTA) from
      Staphylococcus aureus. RESULTS: Following LPS injection, a significant increase
      of 15 miRNAs was observed in the whole blood. Among them, only 3 miRNAs showed up
      regulated expression in the lung, but no miRNAs showed a high expression level in
      the other examined tissues. Upregulated expression of the miRNA targets (let-7d,
      miR-15b, miR-16, miR-25, miR-92a, miR-103, miR-107 and miR-451) following LPS
      injection on real-time RT-PCR was dose- and time-dependent. miRNA induction
      occurred after 2 h and persisted for at least 6 h. Exposure to LPS from different
      bacteria did not induce significantly different expression of these miRNA
      targets. Additionally, significantly lower expression levels of let-7d, miR-25,
      miR-92a, miR-103, and miR-107 were observed in whole blood of Tlr4(-/-) mice. In
      contrast, LTA exposure induced moderate expression of miR-451 but not of the
      other 7 miRNA targets. CONCLUSIONS: We identified a specific whole blood-derived
      miRNA signature in mice exposed to LPS, but not to LTA, from different gram
      negative bacteria. These whole blood-derived miRNAs are promising as biomarkers
      for LPS exposure.

PMID- 22849763
TI  - An iodocyclization approach to substituted 3-iodothiophenes.
AB  - A novel approach to 3-iodothiophenes by direct iodocyclization of alkynylthiol
      derivatives is presented. A variety of 1-mercapto-3-yn-2-ols 5 (readily available
      from alkynylation of the corresponding alpha-mercapto ketones or alpha-mercapto
      esters) were smoothly converted into the corresponding 3-iodothiophene
      derivatives 6 in good yields by reaction with molecular iodine in the presence of
      NaHCO(3) at room temperature in MeCN as the solvent.

PMID- 22849762
TI  - A double-blind randomised controlled trial of a natural oil-based emulsion
      (Moogoo Udder Cream(r)) containing allantoin versus aqueous cream for managing
      radiation-induced skin reactions in patients with cancer.
AB  - BACKGROUND: Radiation-induced skin reaction (RISR) is one of the most common and
      distressing side effects of radiotherapy in patients with cancer. It is featured
      with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning
      sensation. There is a lack of convincing evidence supporting any single practice
      in the prevention or management of RISR. METHODS/DESIGNS: This double-blinded
      randomised controlled trial aims to investigate the effects of a natural oil
      based emulsion containing allantoin (as known as Moogoo Udder Cream(r)) versus
      aqueous cream in reducing RISR, improving pain, itching and quality of life in
      this patient group. One group will receive Moogoo Udder Cream(r). Another group
      will receive aqueous cream. Outcome measures will be collected using patient self
      administered questionnaire, interviewer administered questionnaire and clinician
      assessment at commencement of radiotherapy, weekly during radiotherapy, and four
      weeks after the completion of radiotherapy. DISCUSSION: Despite advances of
      radiologic advances and supportive care, RISR are still not well managed. There
      is a lack of efficacious interventions in managing RISR. While anecdotal evidence
      suggests that Moogoo Udder Cream(r) may be effective in managing RISR, research
      is needed to substantiate this claim. This paper presents the design of a double
      blind randomised controlled trial that will evaluate the effects of Moogoo Udder
      Cream(r) versus aqueous cream for managing in RISR in patients with cancer. TRIAL
      REGISTRATION: ACTRN 12612000568819.

PMID- 22849764
TI  - Name that neurotransmitter: using music to teach psychopharmacology concepts.
AB  - The purpose of this article is to discuss the use of music (i.e., two original
      songs, "Neurotransmitter Twitter" and "Parkinson's Shuffle") to teach aspects of
      psychopharmacology to students in the course Psychiatric/Mental Health Nursing.
      Songs were incorporated in both the clinical and classroom settings. This
      innovative teaching method allowed students the opportunity to revisit the
      information through multiple exposures of the content for reinforcement and
      enhancement of student learning in a fun, creative approach. Brain-based research
      will be discussed, along with the process of development.

PMID- 22849765
TI  - Selecting concepts for a concept-based curriculum: application of a benchmark
      approach.
AB  - In response to a transformational movement in nursing education, faculty across
      the country are considering changes to curricula and approaches to teaching. As a
      result, an emerging trend in many nursing programs is the adoption of a concept
      based curriculum. As part of the curriculum development process, the selection of
      concepts, competencies, and exemplars on which to build courses and base content
      is needed. This article presents a benchmark approach used to validate and
      finalize concept selection among educators developing a concept-based curriculum
      for a statewide nursing consortium. These findings are intended to inform other
      nurse educators who are currently involved with or are considering this
      curriculum approach.

PMID- 22849766
TI  - Predictors of students' success in community college nursing programs.
AB  - Many conceptual models have been applied in the investigation of college
      retention of nursing students. We tested a model that specifies four general
      constructs as predictors of student success in nursing education-dispositional
      factors, career value factors, situational factors, and institutional factors.
      The purpose of this article is to describe predictors of nursing students'
      success, specifically: (a) What factors predict success of nursing students
      graduating from community colleges in California? and (b) What factors predict
      success of nursing students graduating on time from community colleges in
      California? The study design was correlational and descriptive in nature, with a
      convenience sample of six intervention colleges and six matched-pair control
      colleges. Results of the logistic regressions indicated on-time and any-time
      graduations were predicted by higher grade point averages in prenursing and
      science. Higher prenursing grades are positive predictors of graduation;
      improvements in performance prior to commencing nursing education should improve
      student success.

PMID- 22849767
TI  - Precepting and mentoring needs of nursing faculty and clinical instructors:
      fostering career development and community.
AB  - A descriptive survey was conducted to describe (a) perceptions of precepting and
      mentoring at early-, mid-, and late-career phases and (b) the organization's
      support of department members' precepting and mentoring needs. Participants were
      nursing faculty and clinical instructors at a midwestern public university. The
      Measure of Precepting and Mentoring was developed for this study. Findings
      indicate that clinical instructors experience greater precepting and mentoring
      satisfaction than faculty and distance-site department members experience a
      higher level of satisfaction than main-campus department members. Faculty
      expressed the most dissatisfaction for late-career mentoring and organizational
      culture and outcomes. From the qualitative data, three themes emerged: (a) a need
      for precepting and mentoring that changes with time, (b) a lack of an
      organizational precepting and mentoring philosophy and supporting mechanisms, and
      (c) the feeling of together but separate. A model of precepting and mentoring
      emerged from our study.

PMID- 22849768
TI  - Perceptions of healthcare professionals regarding the main challenges and
      barriers to effective hospital infection control in Mongolia: a qualitative
      study.
AB  - BACKGROUND: It is not fully understood why healthcare decision-makers of
      developing countries often give low priority to infection control and why they
      are unable to implement international guidelines. This study aimed to identify
      the main perceived challenges and barriers that hinder the effective
      implementation of infection control programmes in Mongolia. METHODS: In 2008,
      qualitative research involving 4 group and 55 individual interviews was conducted
      in the capital city of Mongolia and two provincial centres. RESULTS: A total of
      87 health professionals participated in the study, including policy and hospital
      level managers, doctors, nurses and infection control practitioners. Thematic
      analysis revealed a large number of perceived challenges and barriers to the
      formulation and implementation of infection control policy. These challenges and
      barriers were complex in nature and related to poor funding, suboptimal knowledge
      and attitudes, and inadequate management. The study results suggest that the
      availability of infection control policy and guidelines, and the provision of
      specific recommendations for low-resource settings, do not assure effective
      implementation of infection control programmes. CONCLUSIONS: The current
      infection control system in Mongolia is likely to remain ineffective unless the
      underlying barriers and challenges are adequately addressed. Multifaceted
      interventions with logistical, educational and management components that are
      specific to local circumstances need to be designed and implemented in Mongolia.
      The importance of international peer support is highlighted.

PMID- 22849769
TI  - Parents' perspectives on centralized cleft services for children: the development
      of a DCE questionnaire.
AB  - OBJECTIVE: Incorporating user's perspectives in healthcare delivery is important.
      Simple questionnaires may not capture these as well as a discrete choice
      experiment (DCE) which enables the exploration of users' trade-offs between
      different service attributes. Qualitative methods are increasingly used to
      improve a DCE's face validity, but few studies adequately describe them. This
      paper describes the qualitative investigations in the development of a DCE
      questionnaire to elicit parents' perspectives on centralized services for
      children with cleft lip and palate. METHODS: Semi-structured telephone interviews
      were conducted with 16 parents from across the UK, except Wales. Data analysis
      was carried out by the constant comparative method. RESULTS: Five attributes and
      their levels were inductively identified: usefulness and amount of information
      (four levels); staff attitude at cleft centres (two levels); continuity of care
      (two levels); personal costs of attending appointments (four levels); and cleft
      centres facilities (two levels). An unexpected finding was that parents' sense of
      responsibility towards their child made a 'willingness-to-travel' attribute
      unacceptable to them, but they were receptive to a 'willingness-to-pay'
      attribute. CONCLUSION: Using qualitative methods with service users in attribute
      development for a DCE helps to uncover issues that may not be apparent to
      researchers or health service staff.

PMID- 22849770
TI  - Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a
      new direct renin inhibitor, and its pharmacokinetic interaction with food and
      midazolam.
AB  - This study investigated the tolerability, safety, pharmacokinetics, and
      pharmacodynamics of ACT-178882, a new direct renin inhibitor, as well as its
      interaction with food and midazolam. Healthy male subjects received either single
      (10-1000 mg) or multiple doses (30-600 mg) administered once daily for 14 days of
      ACT-178882, placebo, or 20 mg enalapril in the fasted state. Following a 2-week
      washout, the single dose of 30 mg ACT-178882 was also administered in the fed
      state. In the multiple-ascending-dose part, subjects were dosed with midazolam on
      days -2, 2, and 12 to investigate interactions with CYP3A4. Dizziness and
      headache were the most frequently reported adverse events. No clinically relevant
      changes occurred for body weight, vital signs, clinical laboratory variables, and
      ECG although both enalapril and ACT-178882 tended to decrease systolic blood
      pressure. Following single doses of ACT-178882, t1/2 and tmax varied from 18.7 to
      24.7 h and from 3 to 5 h, respectively, and food had no significant effect.
      Steady-state conditions were achieved after 4-6 days of dosing and accumulation
      was minimal. ACT-178882 pharmacokinetics were dose proportional. ACT-178882 but
      not enalapril dose-dependently increased Cmax and area under the concentration
      time curve of midazolam. Single and multiple doses of ACT-178882 dose-dependently
      increased active renin and decreased plasma renin activity, whereas enalapril
      increased both variables. No effects on urinary excretion of creatinine,
      potassium, and the 6beta-hydroxycortisol/cortisol ratio were observed, whereas
      sodium and aldosterone excretion was decreased by both ACT-178882 and enalapril.
      The current results with ACT-178882 warrant further clinical investigation of
      this renin inhibitor in hypertensive patients.

PMID- 22849772
TI  - Exploratory investigation of new SHG materials based on galloborates.
AB  - Three new galloborates, namely, GaB(5)O(8)(OH)(2)(en)(2).H(2)O (1),
      LiGa(OH)(BO(3))(H(2)O) (2), and Rb(2)Ga(B(5)O(10))(H(2)O)(4) (3), have been
      synthesized by hydrothermal reactions. Compound 1 is the first example of a
      galloborate that contains an organic component. It crystallizes in space group
      P2(1)/c, and its crystal structure exhibits an infinite zigzag chain consisting
      of [B(5)O(8)(OH)(2)](3-) anions and GaO(2)N(4) octahedra interconnected via
      corner sharing. Compound 2 crystallizes in space group P31c with a layered
      structure composed of GaO(4), LiO(4), and BO(3) building units. Compound 3
      belongs to chiral space group C222(1); the basic building blocks of the structure
      are the [B(5)O(10)](5-) cluster anion and GaO(4) tetrahedron, which are
      interconnected to form a three-dimensional network with tunnels of Ga2B6 eight
      membered rings (8-MRs) which are filled by Rb(+) cations and lattice water
      molecules. Interestingly, Rb(2)Ga(B(5)O(10))(H(2)O)(4) displays a moderate second
      harmonic generation (SHG) response comparable to that of KH(2)PO(4) (KDP), and it
      is phase matchable. Band structure and optical property calculations for
      Rb(2)Ga(B(5)O(10))(H(2)O)(4) based on DFT methods were also performed.

PMID- 22849771
TI  - The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual
      parasites committed to sexual differentiation.
AB  - BACKGROUND: Malaria parasites undergo, in the vertebrate host, a developmental
      switch from asexual replication to sexual differentiation leading to the
      formation of gametocytes, the only form able to survive in the mosquito vector.
      Regulation of the onset of the sexual phase remains largely unknown and
      represents an important gap in the understanding of the parasite's complex
      biology. METHODS: The expression and function of the Nima-related kinase Pfnek-4
      during the early sexual development of the human malaria parasite Plasmodium
      falciparum were investigated, using three types of transgenic Plasmodium
      falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein
      under the control of its cognate pfnek-4 promoter; (ii) episomally expressing
      negative or positive selectable markers, yeast cytosine deaminase-uridyl
      phosphoribosyl transferase, or human dihydrofolate reductase, under the control
      of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite
      transfectants were analysed by fluorescence microscopy and flow cytometry. In
      vitro growth rate and gametocyte formation were determined by Giemsa-stained
      blood smears. RESULTS: The Pfnek-4-GFP protein was found to be expressed in stage
      II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites
      undergoing schizogony. Culture conditions stimulating gametocyte formation
      resulted in significant increase of this schizont subpopulation. Moreover, sorted
      asexual parasites expressing the Pfnek-4-GFP protein displayed elevated
      gametocyte formation when returned to in vitro culture in presence of fresh red
      blood cells, when compared to GFP- parasites from the same initial population.
      Negative selection of asexual parasites expressing pfnek-4 showed a marginal
      reduction in growth rate, whereas positive selection caused a marked reduction in
      parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4
      clones are not affected in their asexual growth and produced normal numbers of
      stage V gametocytes. CONCLUSIONS: The results indicate that Pfnek-4 is not
      strictly gametocyte-specific, and is expressed in a small subset of asexual
      parasites displaying high rate conversion to sexual development. Pfnek-4 is not
      required for erythrocytic schizogony and gametocytogenesis. This is the first
      study to report the use of a molecular marker for the sorting of sexually
      committed schizont stage P. falciparum parasites, which opens the way to
      molecular characterization of this pre-differentiated subpopulation.

PMID- 22849773
TI  - Investigation of poly(lactide) stereocomplexes: 3-armed poly(L-lactide) blended
      with linear and 3-armed enantiomers.
AB  - Stereocomplex poly(lactide)s (sc-PLAs) were obtained from solution blending of 3
      armed poly(L-lactide) (3PLLA) and linear poly(D-lactide) (PDLA) and between
      enantiomeric 3PLAs. Differential scanning calorimetry and wide-angle X-ray
      diffraction results indicated that racemic crystallites were preferentially
      produced in all the binary blends. The melting temperature and fusion enthalpy of
      racemic crystallites were remarkably different through varying the structure,
      constituent, and molecular weight of PLA. Through this investigation, higher
      melting temperatures were obtained in the middle molecular weight binary blends,
      and the highest melt temperature of racemic crystallites reached to 246  degrees
      C, it was the highest reported value until now. In similar molecular weight
      blends (or the linear PLA was similar to each branch of 3PLA enantiomers), with
      the composition of 3PLA increasing, the phase separation molecular weight
      decreased gradually (M(linear/linear blends) > M(linear/3-armed blends) > M(3
      armed/3-armed blends)). The structure distinction between 3PLA and linear PLA
      induced different thermal properties and phase behaviors of the 3PLLA/PDLA and
      3PLLA/3PDLA blends. The thermal properties of these mixtures and its variations
      provided basic data for their industrial applications.

PMID- 22849774
TI  - Identification of 4,5-dihydro-4-hydroxygeldanamycins as shunt products of
      geldanamycin biosynthesis.
AB  - Two new geldanamycin (GDM) analogues, (4S)-4,5-dihydro-4-hydroxygeldanamycin (1)
      and (4R)-4,5-dihydro-4-hydroxygeldanamycin (2), were identified from Streptomyces
      hygroscopicus 17997. Compounds 1 and 2 were not normal intermediates of GDM
      biosynthesis but shunt products of C-4,5 oxidation catalyzed by GdmP, a
      cytochrome P450 oxidase acting as a desaturase in GDM biosynthesis. Preliminary
      assays implied that, compared with GDM, 1 and 2 exhibited decreased cytotoxicity.

PMID- 22849775
TI  - Can we listen in a new way to those who listen to voices?

PMID- 22849776
TI  - Panoptic power and mental health nursing-space and surveillance in relation to
      staff, patients, and neutral places.
AB  - Mental health nurses use manifest and latent approaches for surveillance and
      observation of patients in the context of mental health care. Patient spaces in
      mental health organizations are subtly linked to these different means of
      surveillance. This article investigates these approaches, focusing in particular
      on the variety of spaces patients occupy and differences in the intensity of
      observation that can be carried out in them. The aim is to elaborate on space and
      surveillance in relation to the patients' and nurses' environment in psychiatric
      nursing care. Places where patients were observed were operationalized and
      categorized, yielding three spaces: those for patients, those for staff, and
      neutral areas. We demonstrate that different spaces produce different practices
      in relation to the exercise of panoptic power and that there is room for
      maneuvering and engaging in alternatives to "keeping an eye on patients" for
      nurses in mental health nursing. Some spaces offer asylum from panoptic
      observations and the viewing eyes of psychiatric nurses, but the majority of
      spaces in mental health nursing serve as a field of visibility within which the
      patient is constantly watched.

PMID- 22849777
TI  - Weight changes and characteristics of patients associated with weight gain during
      inpatient psychiatric treatment.
AB  - This study investigated weight changes and patient characteristics associated
      with weight gain in a public psychiatric hospital. A retrospective chart review
      was conducted on a multi-racial population admitted for psychiatric inpatient
      treatment. Patients gained an average of 5.41 pounds during psychiatric
      hospitalization. Patients with normal weight at admission were significantly more
      likely to gain weight compared to overweight or obese patients. Black patients
      showed the greatest weight gain, while Asian patients showed the smallest weight
      gain. This study suggests that it may be possible to identify specific
      demographic characteristics that warrant more intensive clinical evaluation,
      although additional research is necessary.

PMID- 22849778
TI  - Disordered eating among African American and African Caribbean women: the
      influence of intimate partner violence, depression, and PTSD.
AB  - We assessed the influence of intimate partner violence (IPV), depression and post
      traumatic stress disorder (PTSD) on disordered eating patterns (DE) among women
      of African descent through a comparative case-control study (N = 790) in
      Baltimore, MD, and St. Thomas and St. Croix, US Virgin Islands, from 2009-2011.
      IPV, depression and PTSD were independent risk factors in the full sample. The
      relationship between IPV and DE was partially mediated by depression. The
      influence of risk for lethality from violence was fully mediated by depression.
      IPV should be considered in research and treatment of DE and both IPV and DE
      should be assessed when the other or depression is detected.

PMID- 22849779
TI  - Personal characteristics predictive of depressive symptoms in Hispanics with
      heart failure.
AB  - Depression is a significant problem in heart failure (HF). The purposes of this
      study were to assess the prevalence of depressive symptoms in Hispanics with HF
      and to examine the personal characteristics predicting depressive symptoms at
      baseline and at 6-months follow-up in a telephone case management intervention.
      In this secondary data analysis based on 87 subjects, patient characteristics
      hypothesized to influence depressive symptoms included age, gender, education,
      living situation, co-morbidity, social support, New York Heart Association (NYHA)
      class, and acculturation. DSM-IV major depression was present in 39.1% (n = 35)
      of the participants at baseline and 1.1% (n = 1) at the 6-month follow-up. In
      regression analysis, factors associated with depressive symptoms at baseline were
      gender and NYHA class. At 6-month follow-up, acculturation, co-morbidity, and
      NYHA were significantly related to the presence of depressive symptoms.
      Depressive symptoms were highly prevalent in Hispanics with HF. Easily
      identifiable personal characteristics can be useful in designing interventions to
      reduce depression associated with HF.

PMID- 22849780
TI  - Teaching care and cooperation with relatives: video as a learning tool in mental
      health work.
AB  - Empathy is crucial for establishing caring relationships and cooperation with
      relatives of people with severe mental illness. This study describes the use of
      video as a learning tool in a post-bachelor program. A focus group of students
      attended a video session. Based on a phenomenological descriptive analysis, we
      found two major themes: (1) Insight and empathy and (2) Developing clinical
      competence. The first theme relates to increased insight into specific family
      situations, which resulted in new-found engagement and ideas for cooperation. The
      second theme relates to how this increased insight was crucial for re-evaluating
      one's own practice, attitudes, and limitations. This study indicates that the use
      of video develops sensitivity, attitudes, and empathy in a classroom setting.
      Enhanced general competence activates clinical knowledge through an improved
      awareness of relatives' perspectives.

PMID- 22849781
TI  - Evidence based practice: decreasing psychiatric revisits to the emergency
      department.
AB  - Inpatient psychiatric settings anticipate changes in reimbursement that will link
      payment rates to objective quality measures. Readmission rates are expected to be
      one of the quality measures. Inpatient areas are undertaking initiatives to
      decrease readmission rates in preparation for this change. The emphasis on
      avoiding readmission could cause an increase in emergency room revisit rates by
      psychiatric patients. In preparation for this potential impact, the mental health
      emergency service within the Emergency Department of a not-for-profit community
      based hospital implemented a proactive process improvement plan. The plan's goal
      was to insure that all patients' care was provided according to a defined
      standardize best practice process. Steps of the plan focused on (1) improving
      treatment providers' communications across the continuum of care, (2) enhancing
      communication between the mental health emergency department nurses and the on
      call psychiatrists, (3) developing on-line decisional support to enhance
      communication, and (4) providing providers with feedback on the impact of
      changes. Implementation of the improvement process decreased the mean psychiatric
      emergency revisit rate from 5.7% to 4.3% and decreased the variability in monthly
      rates from a range of 1.83%-9.53% to a range of 3.53%-5.56%.

PMID- 22849782
TI  - A multi-modal pilot intervention with violence-exposed mothers in a child
      psychiatric trauma-focused treatment program.
AB  - This multi-method pilot study implemented a relationally-based intervention with
      mothers of school-aged children receiving treatment for exposure to domestic
      violence. Grounded in psychodynamic and attachment theories, the short-term
      intervention consisted of targeted individual and group sessions. Quantitative as
      well as qualitative data were examined for trends and exemplars of important
      process outcomes. Improvements were evidenced in a number of key areas including
      psychiatric symptoms, isolation, defensive avoidance, coping skills,
      attributional style, and reflective functioning. Results converged to portray
      improved functioning in critical areas of dysfunction often displayed by these
      mothers.

PMID- 22849783
TI  - Women's body image: implications for mental health nursing interventions.
AB  - The aim of this concept analysis is to define women's body image in the context
      of mental health and to describe its antecedents and consequences. The analysis
      is grounded in a selective review delimited to literature about women's self
      perceived body image. The psychological, social, and spiritual effects of a
      negative body image will be explored. Implications for mental health clinicians
      and researchers will be presented.

PMID- 22849785
TI  - Health of working mothers and their children.

PMID- 22849786
TI  - Mandatory fortification of bread with iodised salt modestly improves iodine
      status in schoolchildren.
AB  - Iodine deficiency has re-emerged in many parts of the world including the UK,
      Australia and New Zealand (NZ). In 2009, the NZ government introduced the
      mandatory fortification of bread with iodised salt as a strategy to improve
      iodine intakes. The aim of the present study was to assess the impact of
      fortification on the iodine status of NZ schoolchildren. A school-based cluster
      survey was used to randomly select schools from two NZ cities. Children aged 8-10
      years were administered a general questionnaire, and asked to provide a casual
      urine and finger-prick blood sample. The median urinary iodine concentration
      (UIC) of the children (n 147) was 113 MUg/l, which falls between 100 and 199
      MUg/l indicating adequate iodine status; 12 % of children had a UIC < 50 MUg/l
      and 39 % had a UIC < 100 MUg/l. The median serum thyroxine concentration was 115
      nmol/l. The median serum thyroglobulin (Tg) concentration was 10.8 MUg/l and
      falls in the 10.0-19.9 MUg/l range indicative of mild iodine deficiency,
      suggesting that these children still had enlarged thyroid glands. When compared
      with the median UIC of 68 MUg/l reported in the 2002 NZ Children's Nutrition
      Survey, the UIC of children in the present study had increased, which is probably
      caused by the addition of iodised salt to bread. However, the elevated
      concentration of Tg in these children suggests that the increase in UIC is not
      sufficient to ensure that thyroid volume has normalised. The fortification of
      other staple foods, in addition to bread, should be considered to ensure good
      iodine status in NZ children.

PMID- 22849787
TI  - A mobile phone text message program to measure oral antibiotic use and provide
      feedback on adherence to patients discharged from the emergency department.
AB  - OBJECTIVES: Nonadherence to prescribed medications impairs therapeutic benefits.
      The authors measured the ability of an automated text messaging (short message
      service [SMS]) system to improve adherence to postdischarge antibiotic
      prescriptions. METHODS: This was a randomized controlled trial in an urban
      emergency department (ED) with an annual census of 65,000. A convenience sample
      of adult patients being discharged with a prescription for oral antibiotics was
      enrolled. Participants received either a daily SMS query about prescription
      pickup, and then dosage taken, with educational feedback based on their responses
      (intervention), or the usual printed discharge instructions (control). A
      standardized phone follow-up interview was used on the day after the intended
      completion date to determine antibiotic adherence: 1) the participant filled
      prescription within 24 hours of discharge and 2) no antibiotic pills were left on
      the day after intended completion of prescription. RESULTS: Of the 200 patients
      who agreed to participate, follow-up was completed in 144 (72%). From the 144,
      26% (95% confidence interval [CI] = 19% to 34%) failed to fill their discharge
      prescriptions during the first 24 hours, and 37% (95% CI = 29% to 45%) had pills
      left over, resulting in 49% (95% CI = 40% to 57%) nonadherent patients. There
      were no differences in adherence between intervention participants and controls
      (57% vs. 45%; p = 0.1). African American race, greater than twice-daily dosing,
      and self-identifying as expecting to have difficulty filling or taking
      antibiotics at baseline were associated with nonadherence. CONCLUSIONS: Almost
      one-half (49%) of our patients do not adhere to antibiotic prescriptions after ED
      discharge. Future work should improve the design and deployment of SMS
      interventions to optimize their effect on improving adherence to medication after
      ED discharge.

PMID- 22849788
TI  - Transplantation of endothelial progenitor cells ameliorates vascular dysfunction
      and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic
      model.
AB  - BACKGROUND AND AIM: In cirrhosis, sinusoidal endothelial cell injury results in
      increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity,
      leading to portal hypertension. However, the effects of transplanted endothelial
      progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We
      investigated whether EPC transplantation reduces portal hypertension. METHODS:
      Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4)
      ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were
      injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS
      (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were
      examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay
      (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were
      measured. RESULTS: Endothelial progenitor cell transplantation reduced liver
      fibrosis, alpha-smooth muscle actin-positive cells, caveolin expression, ET-1
      concentration and portal venous pressure. EPC transplantation increased hepatic
      blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS
      and isolectin B4 demonstrated that the livers of EPC-transplanted animals had
      markedly increased vascular density, suggesting reconstitution of sinusoidal
      blood vessels with endothelium. CONCLUSIONS: Transplantation of EPCs ameliorates
      vascular dysfunction and portal hypertension, suggesting this treatment may
      provide a new approach in the therapy of portal hypertension with liver
      cirrhosis.

PMID- 22849789
TI  - Comparison of 0.625-mm source computed tomographic images versus 5-mm thick
      reconstructed images in the evaluation for renal calculi in at-risk patients.
AB  - BACKGROUND AND PURPOSE: CT has become a well-established modality in the
      evaluation of urinary calculi. The advent of multidetector CT (MDCT) scanners and
      submillimeter thick slice acquisitions has yielded CT images with even greater
      resolution. MDCT scanners allow for source data slice acquisition with
      submillimeter slice thickness. These source images can then be reconstructed to
      thicker slices for more convenient interpretation of the CT scan. Previous
      authors have looked at the effect of slice thickness on detection of urinary
      calculi. We investigated whether the thin slice source images yielded detection
      of additional stones and the potential significance of detecting these additional
      stones. PATIENTS AND METHODS: Ninety-five consecutive patients who were referred
      to our outpatient imaging center for CT, with a clinical history placing them at
      risk for urinary calculi, were included in the study. RESULTS: In 49 (52%) of the
      95 patients, more calculi were visualized using the 0.625-mm thick images than
      with the 5-mm thick images. In 34 (69%) of these 49 patients, the additional
      findings were thought to be "clinically significant," while in the remaining 15
      (31%) patients, the additional findings were not thought to be clinically
      significant. In 46 (48%) of the 95 patients, there were no additional urinary
      calculi identified on the 0.625-mm thick images compared with that observed on 5
      mm thick images. CONCLUSION: The results from this study encourage reviewing the
      thin slice source images of MDCTs in patients at risk for urinary calculi,
      because important clinical decisions may hinge on the additional findings made on
      these images.

PMID- 22849790
TI  - Cancer awareness among adolescents in Britain: a cross-sectional study.
AB  - BACKGROUND: Little is known about adolescents' cancer awareness and help-seeking
      behaviour in Britain. This study assessed adolescents': awareness of cancer
      symptoms, common cancers, and the relationship between cancer and age;
      anticipated delay and perceived barriers to seeking medical advice; and examined
      variation by age, gender, ethnicity and whether individuals knew someone with
      cancer. METHODS: A survey was conducted using a modified paper version of the
      Cancer Awareness Measure (CAM). The sample included 478 adolescents (male: n =
      250, 52.3%) aged 11-17 years old (mean = 13.8, SD = 1.24) recruited from four
      British schools between August and October 2011. RESULTS: Adolescents' cancer
      awareness was low. Half of all adolescents did not know the most common childhood
      (51%) or teenage (49%) cancers and most (69%) believed cancer was unrelated to
      age. Awareness of cancer symptoms was significantly higher among older
      adolescents (aged 13-17 years) (p = 0.003) and those who knew someone with cancer
      (p < 0.001). Three-quarters (74%) of adolescents indicated they would seek help
      for a symptom they thought might be cancer within 3 days, and half (48%) within
      24 hours. The most endorsed barriers to help-seeking were 'worry about what the
      doctor might find' (72%), being 'too embarrassed' (56%), 'too scared' (54%) and
      'not feeling confident to talk about symptoms' (53%). Endorsement of these
      emotional barriers was significantly higher among females (p <= 0.001).
      CONCLUSION: There are certain groups of adolescents with poor cancer awareness.
      Cancer messages need to be targeted and tailored to particular groups to prevent
      the emergence of health inequalities in adulthood. Interventions to raise
      adolescents' cancer awareness have the potential for a life-long impact on
      encouraging early diagnosis and survival.

PMID- 22849791
TI  - Postmenopausal skin and estrogen.
AB  - The aging global population continues to drive increasing demand for
      cosmaceuticals and cosmetic surgery among older men and women. Since the
      discovery in the 1990s that estrogen receptors are present in skin cells and
      decline in number from the onset of menopause in women, researchers have explored
      a number of ways in which estrogen can improve skin condition. Skin is estrogen
      responsive, and several studies now exist to support the antiaging properties of
      estrogen replacement therapies in postmenopausal women. Both systemic and topical
      estrogens appear to have positive effects on hormonal aging, increasing skin
      collagen content, thickness, elasticity and hydration. Estrogen therapies may
      also improve wound healing and reduce the incidence of wound complications. This
      review explores the potential for targeted estrogen replacement as a therapeutic
      option for long-term skin management in postmenopausal women.

PMID- 22849792
TI  - Single-tube nested real-time PCR as a new highly sensitive approach to trace
      hazelnut.
AB  - Hazelnut is one of the most commonly consumed tree nuts, being largely used by
      the food industry in a wide variety of processed foods. However, it is a source
      of allergens capable of inducing mild to severe allergic reactions in sensitized
      individuals. Hence, the development of highly sensitive methodologies for
      hazelnut traceability is essential. In this work, we developed a novel technique
      for hazelnut detection based on a single-tube nested real-time PCR system. The
      system presents high specificity and sensitivity, enabling a relative limit of
      detection of 50 mg/kg of hazelnut in wheat material and an absolute limit of
      detection of 0.5 pg of hazelnut DNA (1 DNA copy). Its application to processed
      food samples was successfully achieved, detecting trace amounts of hazelnut in
      chocolate down to 60 mg/kg. These results highlight the adequacy of the technique
      for the specific detection and semiquantitation of hazelnut as potential hidden
      allergens in foods.

PMID- 22849793
TI  - Impact of central nervous system (CNS) prophylaxis on the incidence and risk
      factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in
      the rituximab era: a single centre experience and review of the literature.
AB  - Central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma
      (DLBCL) is controversial with even less evidence in the era of R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. We reviewed
      the impact of CNS prophylaxis in DLBCL patients treated with R-CHOP at a tertiary
      care centre over a 7-year period. CNS prophylaxis was recommended for 'higher
      risk' patients and consisted of intrathecal methotrexate and/or high-dose
      methotrexate. Of 214 patients 12.6% received CNS prophylaxis. With a median
      follow-up of 27 months, eight patients (3.7%) developed CNS relapse (75% isolated
      to the CNS and 62.5% as parenchymal brain disease) at a median time of 17 months.
      Patients who did not receive CNS prophylaxis had lower events (2.7%) than those
      who did (11.1%). Half of the CNS relapses occurred in testicular lymphoma
      patients, 75% of whom had received CNS prophylaxis. In multivariate analysis,
      testicular involvement was the only significant prognostic factor for CNS relapse
      (hazard ratio 33.5, P < 0.001). In conclusion, CNS relapse in DLBCL appears to
      present as a later, more isolated parenchymal event and at a lower rate in the
      rituximab era compared with historical data. R-CHOP may negate the need for CNS
      prophylaxis with the exception of testicular lymphoma.

PMID- 22849794
TI  - Heteropolyacid-catalyzed direct deoxygenation of propargyl and allyl alcohols.
AB  - The combination of H(3)[PW(12)O(40)].nH(2)O (1 mol %) and Et(3)SiH led to the
      direct catalytic deoxygenation of propargyl alcohols, in which proper solvent
      selection Cl(CH(2))(2)Cl vs CF(3)CH(2)OH was the key to obtaining better product
      yields. Under similar conditions, the deoxygenation of allyl alcohols proceeded
      to give thermodynamically stable alkenes with migration of the double bonds in
      good yields.

PMID- 22849795
TI  - The processing of lexical tones by young Chinese children.
AB  - The current study examined five- and seven-year-old Mandarin-speaking children's
      processing of lexical tones in relation to speech segments by varying onset and
      rime in an oddity task (onset+/-rime+/-). Results showed that children
      experienced more difficulty in lexical tone oddity judgment when rimes differed
      across monosyllables (e.g. onset+rime-) than when onsets differed (e.g. onset
      rime+). This finding suggests that vowels interfere more than consonants in
      lexical tone processing. Seven-year-olds consistently outperformed five-year
      olds, suggesting that the growth of metalinguistic awareness and literacy
      exposure may play a joint role in the development of lexical tone processing
      skills.

PMID- 22849796
TI  - The first years of the aberration-corrected electron microscopy century.
AB  - Aberration correction, after a 50 year incubation period of developing ideas and
      techniques while awaiting enabling technology, has transformed electron
      microscopy during the first dozen years of the 21st century. Some of the
      conditions that accompanied this transformation, the required complexity and its
      effect on the way microscopy is pursued, recent results that promise to change
      the field, and directions for the future are briefly described.

PMID- 22849797
TI  - Operation of TEAM I in a user environment at NCEM.
AB  - TEAM I is the final product of the Transmission Electron Aberration-corrected
      Microscope (TEAM) Project, a collaborative project funded by the Department of
      Energy with the goal of designing and building a platform for a next generation
      aberration-corrected electron microscope capable of image resolution of up to 50
      pm. The TEAM instrument incorporates a number of new technologies, including
      spherical- and chromatic-aberration correction, an all-piezo-electric sample
      stage and an active-pixel direct electron detector. This article describes the
      functionality of this advanced instrumentation, its response to changes in
      environment or operating conditions, and its stability during daily operation
      within the National Center for Electron Microscopy user facility.

PMID- 22849798
TI  - Challenges to quantitative multivariate statistical analysis of atomic-resolution
      X-ray spectral.
AB  - A new aberration-corrected scanning transmission electron microscope equipped
      with an array of Si-drift energy-dispersive X-ray spectrometers has been utilized
      to acquire spectral image data at atomic resolution. The resulting noisy data
      were subjected to multivariate statistical analysis to noise filter, remove an
      unwanted and partially overlapping non-sample-specific X-ray signal, and extract
      the relevant correlated X-ray signals (e.g., channels with L and K lines). As an
      example, the Y2Ti2O7 pyrochlore-structured oxide (assumed here to be ideal) was
      interrogated at the [011] projection. In addition to pure columns of Y and Ti, at
      this projection, there are also mixed 50-50 at. % Y-Ti columns. An attempt at
      atomic-resolution quantification is presented. The method proposed here is to
      subtract the non-column-specific signal from the elemental components and then
      quantify the data based upon an internally derived k-factor. However, a
      theoretical basis to predict this non-column-specific signal is needed to make
      this generally applicable.

PMID- 22849799
TI  - Ad hoc auto-tuning of aberrations using high-resolution STEM images by
      autocorrelation function.
AB  - A method for measurement of the aberration status from high-resolution dark-field
      images is developed using scanning transmission electron microscopy (STEM),
      called the Segmented Image Autocorrelation function Matrix (SIAM). The method
      employs an autocorrelation function from the segmented area in the defocused STEM
      images from an aligned crystalline specimen to measure the defocus and twofold
      astigmatism for the probe-forming system. The values measured using this method
      can be fed directly back to the instrument by changing the strength of the
      stigmator and the objective lens of the microscope. It is successfully
      demonstrated that the feedback system can automatically correct the defocus and
      twofold astigmatism of the microscope after several iterations using practical
      STEM images from an actual crystalline specimen.

PMID- 22849800
TI  - Introduction: modern imaging in biology and medicine: papers from the seventh
      omaha imaging symposium, april 2011.

PMID- 22849801
TI  - Distinguishing positional uncertainty from true mobility in single-molecule
      trajectories that exhibit multiple diffusive modes.
AB  - Although imperfect spatial localization in single-molecule object tracking
      experiments has long been recognized to induce apparent motion in an immobile
      population of molecules, this effect is often ignored or incorrectly analyzed for
      mobile molecules. In particular, apparent motion due to positional uncertainty is
      often incorrectly assigned as a distinct diffusive mode. Here we show that, due
      to both static and dynamic contributions, positional uncertainty does not
      introduce a new apparent diffusive mode into trajectories, but instead causes a
      systematic shift of each measured diffusion coefficient. This shift is relatively
      simple: a factor of sigma2/Deltat is added to each diffusion coefficient, where
      sigma is the positional uncertainty length scale and Deltat is the time interval
      between observations. Therefore, by calculating the apparent diffusion
      coefficients as a function of Deltat, it is straightforward to separate the true
      diffusion coefficients from the effective positional uncertainty. As a concrete
      demonstration, we apply this approach to the diffusion of the protein fibrinogen
      adsorbed to a hydrophobic surface, a system that exhibits three distinct modes of
      diffusion.

PMID- 22849802
TI  - Cross-section and staining-based techniques for investigating organic materials
      in painted and polychrome works of art: a review.
AB  - The article presents a review of the use of cross-section and staining techniques
      for investigating natural organic materials (mainly proteinaceous and oil-based
      binders/varnishes) in painted and polychrome artworks, considering the
      requirements of conservation practice and routine diagnostics. The reviewed
      literature calls attention to the importance of using cross sections to prepare
      samples for optical microscopy and to different properties of embedding resins;
      the most appropriate instrumental conditions for optical microscopy; and the
      advantages and disadvantages of the most common staining techniques. A few case
      studies were selected to illustrate the use of autofluorescence (intrinsic
      fluorescence) and induced fluorescence (using specific staining tests and
      fluorophore-labeled antibodies) for mapping and identifying organic paint
      materials in cross sections. New directions of research in cross-section analyses
      and fluorescence-based techniques for the identification and mapping of artistic
      materials are presented. The complementary use of different stains on the same
      cross section, further exploration of intrinsic and induced fluorescence of aged
      versus fresh materials, and applicability of cross-section observation and
      staining as complementary methods for assessing the effectiveness of restoration
      treatments, such as cleaning and consolidation, are discussed in the last section
      of the article.

PMID- 22849803
TI  - Scanning tunneling microscopy study of alpha,omega-dihexylsexithiophene adlayers
      on Au(111): a chiral separation induced by a surface.
AB  - The self-assembly of alpha,omega-dihexylsexithiophene molecules on an Au(111)
      surface was examined by using scanning tunneling microscopy at room temperature,
      revealing the internal molecular structures of the sexithiophene backbones and
      the hexyl side chains. The alpha,omega-dihexylsexithiophene formed a large and
      well-ordered monolayer in which the molecule lay flatly on the Au(111) surface
      and was separated into two chiral domains. A detailed observation reveals that
      the admolecules were packed in one lamellae with their molecular axis aligned
      along the main axis of the Au(111) substrate with their hexyl chains deviated
      from <110> direction of the Au(111) substrate by 12 +/- 0.5 degrees . In contrast
      to the behavior in the three-dimensional bulk structure, flat-lying adsorption
      introduced molecular chirality: right- and left-handed molecules separate into
      domains of two different orientations, which are mirror symmetric with respect to
      the <121> direction of the Au(111) substrate. Details of the adlayer structure
      and the chiral self-assembly were discussed here.

PMID- 22849804
TI  - Fabrication of anisotropic porous silica monoliths by means of magnetically
      controlled phase separation in sol-gel processes.
AB  - Sol-gel accompanied by phase separation is an established method for the
      preparation of porous silica monoliths with well-defined macroporosity, which
      find numerous applications. In this work, we demonstrate how the addition of
      (superpara)magnetic nanocolloids as templates to a system undergoing a sol-gel
      transition with phase separation leads to the creation of monoliths with a
      strongly anisotropic structure. It is known that magnetic nanocolloids respond to
      the application of an external magnetic field by self-assembling into columnar
      structures. The application of a magnetic field during the chemically driven
      spinodal decomposition induced by the sol-gel transition allows one to break the
      symmetry of the system and promote the growth of elongated needle-like silica
      domains incorporating the magnetic nanocolloids, aligned in the direction of the
      field. It is found that this microstructure imparts a strong mechanical
      anisotropy to the materials, with a ratio between the Young's modulus values
      measured in a direction parallel and perpendicular to the one of the field as
      high as 150, and an overall smaller average macropores size as compared to
      isotropic monoliths. The microstructure and properties of the porous monoliths
      can be controlled by changing both the system composition and the strength of the
      applied magnetic field. Our monoliths represent the first example of materials
      prepared by magnetically controlling a phase transition occurring via spinodal
      decomposition.

PMID- 22849805
TI  - Specificity of motor learning in simulator training of endoscopic-surgery skills.
AB  - The introduction of simulators for the practice of endoscopic-surgery sensori
      motor skills opens a wide range of design options. An obvious one is augmented
      visual information early in practice, in particular a direct view of the site
      instead of the endoscopic view. We studied the effects of such augmented visual
      information on the simulated ablation of tissue with straight, horizontal and
      parallel cuts. Direct view had an immediate beneficial effect on performance as
      compared with endoscopic-view practice. However, in subsequent tests with
      endoscopic view the benefits disappeared and turned into costs for some aspects
      of performance, e.g., duration. This finding highlights for a simulated surgical
      task that optimisation of practice by a performance criterion may not result in
      optimisation by a transfer criterion. PRACTITIONER SUMMARY: Endoscopic surgery
      represents a challenge for human sensori-motor skills, but new simulator-based
      training methods give leeway for optimisation. A candidate is augmented visual
      feedback, in particular a direct rather than endoscopic view of the site.
      However, performance becomes dependent on the augmented feedback so that the
      costs outweigh the benefits.

PMID- 22849806
TI  - Cervical and Oral Screening for HR-HPV types 16 and 18 among Sudanese Women
      Cervical Lesions.
AB  - OBJECTIVE: This study examined whether there is a positive correlation existed
      between cervical and oral High Risk-Human Papilloma Viruses (HR-HPV) types 16, 18
      infections in patients with clinically confirmed cervical lesions. METHODS: In
      this study 50 participants were included (40 were cases and 10 were controls).
      One hundred DNA materials (50 were cervical and 50 were oral epithelial tissues)
      were analyzed using HR-HPV subtypes 16 and 18 specific PCR probes. RESULTS: Of
      the 40 cases, HR-HPV 16, 18 were identified in 16/40 (40%), of the cervical
      tissues of whom 8/16 (50%) were positive for HPV 16; 6/16 (37.5%) were identified
      with HR-HPV 18, and 2/16 (12.5%) were detected with both HR-HPV subtypes. All of
      the clinically healthy cases were found negative. Only one oral tissue sample
      (case) was 1/40 (2.5%) was found positive for HPV subtype16. CONCLUSION: The
      frequency of infection with HR-HPV subtypes 16 and 18 is high among Sudanese
      women with cervical lesions and suggests a role of HR-HPV in the development of
      cervical cancer in Sudan. No correlation between cervical and oral HPV infection
      was noted. Further study with screening of large number of patients with cervical
      cancer is recommended for further clarification of these findings.

PMID- 22849807
TI  - Ultrasound biomicroscopy diagnosis of an axenfeld loop.
AB  - A 67-year-old man was referred for evaluation of a small mass on the sclera of
      the right eye. Ultrasound biomicroscopy of the mass suggested the diagnosis of
      Axenfeld loop.

PMID- 22849809
TI  - Exploring mathematics problems prepares children to learn from instruction.
AB  - Both exploration and explicit instruction are thought to benefit learning in many
      ways, but much less is known about how the two can be combined. We tested the
      hypothesis that engaging in exploratory activities prior to receiving explicit
      instruction better prepares children to learn from the instruction. Children (159
      second- to fourth-grade students) solved relatively unfamiliar mathematics
      problems (e.g., 3+5=4+?) before or after they were instructed on the concept of
      mathematical equivalence. Exploring problems before instruction improved
      understanding compared with a more conventional "instruct-then-practice"
      sequence. Prompts to self-explain did not improve learning more than extra
      practice. Microgenetic analyses revealed that problem exploration led children to
      more accurately gauge their competence, attempt a larger variety of strategies,
      and attend more to problem features-better preparing them to learn from
      instruction.

PMID- 22849808
TI  - Sex and gestational age effects on auditory brainstem responses in preterm and
      term infants.
AB  - BACKGROUND: Some studies find delayed development of the auditory brainstem in
      preterm infants, but others do not. AIM: To compare auditory brainstem responses
      (ABRs) in healthy preterm and term infants depending on sex and gestational age
      (GA). METHODS: Participants were 111 preterm (27-36weeks GA) and 92 term (37
      41weeks GA) infants. ABR tests were conducted at 6weeks (corrected age if
      preterm). RESULTS: There were no overall differences between term and preterm
      groups in ABRs. However, males showed longer latencies for waves III, V, and I
      III, III-V, and I-V intervals and smaller amplitudes for wave III and V than
      females in both preterm and term groups (all p values<=.01). A 3-way interaction
      between group, sex, and GA (p<.05) showed that preterm males with later GA had
      longer wave I-V interval, whereas term females with later GA showed shorter wave
      I-V interval. Growth velocity predicted wave I-V interval in preterm infants,
      controlling for other factors (male: p=.07, female: p<.05). CONCLUSION: ABRs in
      preterm and term infants were similar at 6weeks (corrected age if preterm), but
      males had less advanced ABRs than females. More rapid growth predicted less
      mature ABR in later GA preterm infants in this setting where they were unlikely
      to receive extra iron. The roles of GA, growth, and iron balance in ABR
      development warrant further study.

PMID- 22849810
TI  - The role of expectations in children's experience of novel events.
AB  - The expectations children bring to interactions, as well as the information they
      receive prior to them, may be important for children's experiences of new adults.
      In this study, 148 children (8-13 years old) reported on their expectations of
      adults, received one of three types of information about a new adult (positive,
      realistic, or control), and then "interacted" with a videotaped "controlling"
      adult. The effect of information type depended on children's age and prior
      expectations, with expectancy effects emerging in the context of positive
      information at the younger end of our age range and in the context of realistic
      information at the older end of our age range. Furthermore, the more expectations
      exceeded perceptions (i.e., the more disappointment), the lower children's
      rapport, affect, and prosocial intentions were and the more internal causal
      attributions they made. Results are discussed in terms of their theoretical and
      applied contributions.

PMID- 22849811
TI  - Luminescence properties of silicon-cellulose nanocomposite.
AB  - We have characterized the structure and luminescence properties for two
      component material composed of nanocrystalline cellulose and nanocrystalline
      (less to 100 nm) silicon powder. An efficient and stable photoluminescence of
      nanocomposite, resistant to the influence of gas-phase oxidants, has been found.
      The obtained material has electret-like properties and demonstrates the
      possibility of multiple-recharging in an electric field near 5.103 V/cm at
      temperatures ranging from -70 degrees C to 100 degrees C. The presence of the
      electric field, as well as ozone or low-temperature plasma treatment, does not
      change the luminescence spectrum due to quantum size properties of silicon
      nanoparticles. We believe that these particles may appear in two states: both
      embedded in a cellulose matrix and in the form of mechanical mixture.

PMID- 22849812
TI  - Anti-inflammatory effect of pachymic acid promotes odontoblastic differentiation
      via HO-1 in dental pulp cells.
AB  - OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation
      in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom
      Formitopsis niagra is examined to determine whether it affects pulpal
      inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND
      METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory
      character and odontoblast differentiation by pachymic acid were analyzed by
      Western blotting, alkaline phosphatase activity, and alizarin red S staining. To
      understand the mechanism of pachymic acid via HO-1 induction, the cells were
      treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced
      pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs
      treated with pachymic acid affected anti-inflammatory effect and induction of
      odontoblast differentiation through increasing HO-1 expression. In addition,
      pachymic acid has potent cytoprotection and mineralization under H2O2 treatment.
      Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF
      kappaB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2)
      translocation into nucleus. Overall, NF-kappaB and Nrf2 translocation were
      regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti
      inflammatory function and odontoblast differentiation via HO-1 pathway. These
      results suggested that pachymic acid may be applicable for prevention of oral
      inflammation or to improve dentin mineralization against several stresses.

PMID- 22849813
TI  - Bifunctional mixed-lanthanide cyano-bridged coordination polymers
      Ln(0.5)Ln'(0.5)(H2O)5[W(CN)8] (Ln/Ln' = Eu3+/Tb3+, Eu3+/Gd3+, Tb3+/Sm3+).
AB  - A new family of mixed-lanthanide cyano-bridged coordination polymers
      Ln(0.5)Ln'(0.5)(H(2)O)(5)[W(CN)(8)] (where Ln/Ln' = Eu(3+)/Tb(3+), Eu(3+)/Gd(3+),
      and Tb(3+)/Sm(3+)) containing two lanthanide and one transition metal ions were
      obtained and characterized by X-ray diffraction, photoluminescence spectroscopy,
      magnetic analyses, and theoretical computation. These compounds are isotypical
      and crystallize in the tetragonal system P4/nmm forming two-dimensional grid-like
      networks. They present a magnetic ordering at low temperature and display the red
      Eu(3+) ((5)D(0) -> (7)F(0-4)) and green Tb(3+) ((5)D(4) -> (7)F(6-2))
      characteristic photoluminescence. The Tb(0.5)Eu(0.5)(H(2)O)(5)[W(CN)(8)] compound
      presents therefore green and red emission and shows Tb(3+)-to-Eu(3+) energy
      transfer.

PMID- 22849815
TI  - Conceptual distance and word learning: patterns of acquisition in Samoan-English
      bilingual children.
AB  - This study investigated cross-linguistic influence in acquisition of a second
      lexicon, evaluating Samoan-English sequentially bilingual children (initial mean
      age 4 ; 9) during their first 18 months of school. Receptive and Expressive
      Vocabulary tasks evaluated acquisition of four word types: cognates, matched
      nouns, phrasal nouns and holonyms. Each word type had varying phonological and
      conceptual difference between Samoan (L1) and English (L2). Results highlighted
      conceptual distance between L1 and L2 as a key factor in L2 lexical acquisition.
      The children acquired L2 lexical items earlier if their conceptual representation
      was similar to that of L1. Words with greater conceptual distance between L1 and
      L2 emerged more slowly. This suggests that L1 knowledge influences L2 lexical
      consolidation for sequential bilinguals. Words that require a conceptual shift
      from L1 take longer to consolidate and strengthen within the L2 lexicon.

PMID- 22849814
TI  - Cardiovascular protection of magnolol: cell-type specificity and dose-related
      effects.
AB  - Magnolia officinalis has been widely used in traditional Chinese medicine.
      Magnolol, an active component isolated from Magnolia officinalis, is known to be
      a cardiovascular protector since 1994. The multiplex mechanisms of magnolol on
      cardiovascular protection depends on cell types and dosages, and will be reviewed
      and discussed in this article. Magnolol under low and moderate dosage possesses
      the ability to protect heart from ischemic/reperfusion injury, reduces
      atherosclerotic change, protects endothelial cell against apoptosis and inhibits
      neutrophil-endothelial adhesion. The moderate to high concentration of magnolol
      mainly acts on smooth muscle cells and platelets. Magnolol induces apoptosis in
      vascular smooth muscle cells at moderate concentration and inhibits proliferation
      at moderate and high concentration. High concentration of magnolol also abrogates
      platelet activation, aggregation and thrombus formation. Magnolol also serves as
      an smooth muscle relaxant only upon the high concentration. Oral intake of
      magnolol to reach the therapeutic level for cardiovascular protection is
      applicable, thus makes magnolol an agent of great potential for preventing
      cardiovascular diseases in high-risk patients.

PMID- 22849816
TI  - An innovative pre-ripening drying method to improve the quality of pasta filata
      cheeses.
AB  - In order to optimise the pre-ripening of pasta filata cheeses, two traditional
      Italian cheeses, Caciocavallo and Scamorza, were dried for different times at 15 
      degrees C, 50% relative humidity and airflow rate of 1000 m3/h, by using a pre
      ripening plant. During ripening, microbiological, chemical-physical and sensorial
      analyses were applied to the products in order to evaluate the impact of the
      innovative pre-ripening technique used on the cheese characteristics. The used
      plant led to commercial time saving and to the standardisation of the process,
      making it unaffected by the effects of temperature and humidity variations,
      common in small industries. The final products showed good chemical-physical and
      sensorial qualities and resulted in a higher microbiological safety, preserving
      their traditional characteristics.

PMID- 22849817
TI  - Early angiographic embolization is more effective than delayed angiographic
      embolization in patients with duodenal ulcer bleeding.
AB  - BACKGROUND AND AIM: Though angiographic embolization (AE) is a type of effective
      treatment modality for duodenal ulcer bleeding, the optimum time at which to
      perform the procedure, early or delayed, is unknown. The authors compared the
      prognosis of early AE (EAE) and delayed AE (DAE) in patients with duodenal ulcer
      bleeding. METHODS: A total of 54 patients with duodenal ulcer bleeding were
      evaluated with first-look endoscopy followed by AE. The patients were divided
      into two groups, the EAE group and DAE group, according to endoscopic attempts to
      stop the bleeding during the first-look endoscopy. RESULTS: The success rate of
      AE, rebleeding rate, and number of patients who underwent surgery was not
      significantly different between the EAE group and DAE group (91.3% vs 93.5%,
      21.7% vs 29.0% and 4.3% vs 16.1%, respectively; P > 0.05). With respect to death
      and intensive care unit (ICU) care rate, multivariate analysis showed more
      favorable results in the EAE group (0% vs 22.6%, P = 0.016 and 4.3% vs 57.4%, P =
      0.003, respectively). Multivariate analysis also showed that prolonged
      prothrombin time (PT) > 1.2 international normalized ratio and the endoscopic
      attempt were independent factors associated with ICU care. CONCLUSION: When the
      AE was performed early with correction for prolonged PT, the patients with
      duodenal ulcer bleeding had a more favorable prognosis.

PMID- 22849818
TI  - Beneficial immunostimulatory effect of short-term Chlorella supplementation:
      enhancement of natural killer cell activity and early inflammatory response
      (randomized, double-blinded, placebo-controlled trial).
AB  - BACKGROUND: In vitro and animal studies have demonstrated that Chlorella is a
      potent biological response modifier on immunity. However, there were no direct
      evidences for the effect of Chlorella supplementation on immune/inflammation
      response in healthy humans. METHODS: This study was designed for an 8-week
      randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or
      Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer
      (NK) cells and serum concentrations of interferon-gamma, interleukin-1beta and
      interleukin-12 were measured. RESULTS: After the 8-week, serum concentrations of
      interferon-gamma (p<0.05) and interleukin-1beta (p<0.001) significantly increased
      and that of interleukin-12 (p<0.1) tended to increase in the Chlorella group. The
      increments of these cytokines after the intervention were significantly bigger in
      the Chlorella group than those in the placebo group. In addition, NK cell
      activities (%) were significantly increased in Chlorella group, but not in
      Placebo group. The increments of NK cell activities (%) were also significantly
      bigger in the Chlorella group than the placebo group. Additionally, changed
      levels of NK cell activity were positively correlated with those of serum
      interleukin-1beta (r=0.280, p=0.047) and interferon-gamma (r=0.271, p<0.005).
      Signficantly positive correlations were also observed among the changed levels of
      serum cytokines; between interferon-gamma and interleukin-1beta (r=0.448,
      p<0.001), between interleukin-12 and interleukin-1beta (r=0.416, p=0.003) and
      between interleukin-12 and interferon-gamma (r=0.570, p<001). CONCLUSION: These
      results may suggest a beneficial immunostimulatory effect of short-term Chlorella
      supplementation which enhances the NK cell activity and produces interferon-gamma
      and interleukin-12 as well as interleukin-1beta, the Th-1 cell-induced cytokines
      in healthy people.

PMID- 22849819
TI  - Disagreement between emergency physician and inpatient physician diagnosis of
      infection in older adults admitted from the emergency department.
AB  - OBJECTIVES: Older adults with infection are at increased risk of misdiagnosis
      while they are patients in the emergency department (ED) due to the common
      presence of nonspecific signs and symptoms. The primary objective was to
      determine the proportion of admitted older adult patients thought by the
      emergency physician (EP) to be infected, as compared with the diagnostic
      impression of inpatient physicians. The secondary objective was to determine the
      agreement between EP and inpatient physician diagnosis of specific infection
      types. METHODS: The authors conducted a prospective, observational, convenience
      sampling of a cohort of ED patients >=65 years old admitted to the hospital with
      diagnoses of acute infection. EPs noted at least one suspected source of
      infection. Inpatient diagnosis of infection was determined by chart review of the
      inpatient chart. Outcomes included the presence of any infection and of specific
      infectious sources diagnosed within 48 hours of admission. EP and inpatient
      diagnoses were compared using proportions, positive and negative likelihood
      ratios (LR+ and LR-), and the phi coefficient. RESULTS: The study included 103
      patients diagnosed with a suspected infection by the EP. Nineteen patients
      (18.4%, 95% confidence interval [CI] = 11.5% to 27.3%) were not diagnosed with
      any infection by the inpatient physician. For specific infection sources, ED
      diagnosis of bloodstream infection often did not agree with the inpatient
      diagnosis. Sensitivity was 40.0% and specificity 78.4% with an LR+ of 1.85 and LR
      of 0.76. The phi coefficient was 0.15. EPs overdiagnosed pulmonary infection,
      with 72.1% specificity and an LR+ of 3.24. EP diagnosis had good accuracy for
      skin and soft tissue infection (sensitivity = 78.6% and specificity = 96.6%),
      with adequate LRs (LR+ of 23.3 and LR- of 0.22). Urinary tract infection (UTI)
      was underdiagnosed in the ED (sensitivity = 58.3%), but it is unclear if this is
      due to true ED underdiagnosis or due to overdiagnosis of UTI in the inpatient
      setting. CONCLUSIONS: In older patients admitted from the ED, the provisional ED
      diagnosis and the inpatient diagnosis of an acute infection often disagree. In
      this sample, 18% of older ED patients diagnosed with infection during an ED stay
      were not diagnosed as infected by the inpatient physician. Regarding infection
      types, EPs were poor at diagnosing bacteremia and overdiagnosed pulmonary
      infections. EP diagnosis of skin and soft tissue infection generally agreed with
      the inpatient physician. There was also disagreement regarding presence of UTI,
      but the true nature of this difference is unclear from the data obtained in this
      study.

PMID- 22849820
TI  - Oxidative stress as a therapeutic target in globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD, Krabbe Disease) is a lysosomal storage disease,
      resulting from the genetic deficiency of galactosylceramidase (GALC). This
      disease is marked by accumulation of the cytotoxic lipid psychosine (Psy).
      Psychosine is known to induce oxidative stress in cultured cells, and this stress
      can be ameliorated through co-treatment with the antioxidant N-acetyl cysteine
      (NAC). Oxidative stress has also been observed in vivo in the mouse model of GLD,
      the Twitcher mouse (Twi). We hypothesized that treating oxidative stress with
      NAC; either alone or in combination with bone marrow transplant (BMT) would
      improve the course of disease. All breeding cages were maintained on water
      containing NAC. Once born, the pups received IP boluses of NAC three times per
      week, and were maintained on NAC-containing water. A separate cohort of animals
      received the same regimen of NAC in addition to a BMT on post-natal days 2-3.
      Although NAC lowers the level of oxidized proteins in the brains of Twi mice, and
      dramatically improves immunohistochemical markers of disease, neither treatment
      results in any clinical improvements in the Twi mouse. Our data suggest that
      oxidative stress may be sufficiently down-stream in the pathogenic cascade
      initiated by Psy accumulation as to be difficult or impossible to treat with
      standard pharmacologic agents. It is possible that NAC may synergize with other
      therapies or combinations of therapies. A better understanding of the initiating
      effects of Psy toxicity and oxidative damage may uncover treatable therapeutic
      targets.

PMID- 22849822
TI  - Two-photon imaging of spinal cord cellular networks.
AB  - Two-photon microscopy enables high-resolution in vivo imaging of cellular
      morphology and activity, in particular of population activity in complex neuronal
      circuits. While two-photon imaging has been extensively used in a variety of
      brain regions in different species, in vivo application to the vertebrate spinal
      cord has lagged behind and only recently became feasible by adapting and refining
      the experimental preparations. A major experimental challenge for spinal cord
      imaging is adequate control of tissue movement, which meanwhile can be achieved
      by various means. One set of studies monitored structural dynamics of neuronal
      and glial cellular components in living animals using transgenic mice with
      specific expression of fluorescent proteins. Other studies employed in vivo
      calcium imaging for functional measurements of sensory-evoked responses in
      individual neurons of the dorsal horn circuitry, which at present is the only
      part of rodent spinal cord grey matter accessible for in vivo imaging. In a
      parallel approach, several research groups have applied two-photon imaging to
      sensorimotor circuits in the isolated spinal cord (in vitro) to provide
      complementary information and valuable new perspectives on the function of
      specific interneuron types in locomotor-related networks. In this review we
      summarize recent results from these types of high-resolution two-photon imaging
      studies in the spinal cord and provide experimental perspectives for improving
      and extending this approach in future applications.

PMID- 22849821
TI  - Genetic basis of human circadian rhythm disorders.
AB  - Circadian rhythm disorders constitute a group of phenotypes that usually present
      as altered sleep-wake schedules. Until a human genetics approach was applied to
      investigate these traits, the genetic components regulating human circadian
      rhythm and sleep behaviors remained mysterious. Steady advances in the last
      decade have dramatically improved our understanding of the genes involved in
      circadian rhythmicity and sleep regulation. Finding these genes presents new
      opportunities to use a wide range of approaches, including in vitro molecular
      studies and in vivo animal modeling, to elevate our understanding of how sleep
      and circadian rhythms are regulated and maintained. Ultimately, this knowledge
      will reveal how circadian and sleep disruption contribute to various ailments and
      shed light on how best to maintain and recover good health.

PMID- 22849823
TI  - Approach to polysubstituted 4-pyridones from N-aryl acetoacetamides via a N to C
      1,3-acyl migration mediated by sodium persulfate.
AB  - Mediated by sodium persulfate (Na(2)S(2)O(8)), a series of polysubstituted 4
      pyridones were synthesized via self-condensation of N-aryl acetoacetamides,
      during which a novel N to C 1,3-acyl migration should be involved. The structure
      of 4-pyridone was unequivocally confirmed by X-ray diffraction analysis. However,
      the self-condensation of N-benzyl acetoacetamides under the same condition gave
      polysubstituted 2-pyridones instead of 4-pyridones.

PMID- 22849824
TI  - A reaction-diffusion mechanism influences cell lineage progression as a basis for
      formation, regeneration, and stability of intestinal crypts.
AB  - BACKGROUND: Colon crypts, a single sheet of epithelia cells, consist of a
      periodic pattern of stem cells, transit-amplifying cells, and terminally
      differentiated cells that constantly renew and turnover. Experimental evidence
      suggests that Wnt signaling promotes and regulates stem cell division,
      differentiation, and possible cell migrations while intestinal BMP signaling
      inhibits stem cell self-renewal and repression in crypt formation. As more
      molecular details on Wnt and BMP in crypts are being discovered, little is still
      known about how complex interactions among Wnt, BMP, and different types of
      cells, and surrounding environments may lead to de novo formation of multiple
      crypts or how such interactions affect regeneration and stability of crypts.
      RESULTS: We present a mathematical model that contains Wnt and BMP, a cell
      lineage, and their feedback regulations to study formation, regeneration, and
      stability of multiple crypts. The computational explorations and linear stability
      analysis of the model suggest a reaction-diffusion mechanism, which exhibits a
      short-range activation of Wnt plus a long-range inhibition with modulation of BMP
      signals in a growing tissue of cell lineage, can account for spontaneous
      formation of multiple crypts with the spatial and temporal pattern observed in
      experiments. Through this mechanism, the model can recapitulate some distinctive
      and important experimental findings such as crypt regeneration and crypt
      multiplication. BMP is important in maintaining stability of crypts and loss of
      BMP usually leads to crypt multiplication with a fingering pattern. CONCLUSIONS:
      The study provides a mechanism for de novo formation of multiple intestinal
      crypts and demonstrates a synergetic role of Wnt and BMP in regeneration and
      stability of intestinal crypts. The proposed model presents a robust framework
      for studying spatial and temporal dynamics of cell lineages in growing tissues
      driven by multiple signaling molecules.

PMID- 22849825
TI  - Plant growth promoting potential and soil enzyme production of the most abundant
      Streptomyces spp. from wheat rhizosphere.
AB  - AIM: To evaluate the plant growth promotion (PGP) potential and soil enzyme
      production under solid state fermentation (SSF) by most abundant Streptomyces
      spp. isolated from the wheat rhizosphere and to evaluate their effect on plant
      growth parameters. METHODS AND RESULTS: Actinomycetes were isolated from wheat
      rhizosphere and screened for PGP activities. Three actinomycete isolates having
      significantly higher PGP activities (Streptomyces rochei IDWR19, Streptomyces
      carpinensis IDWR53, Streptomyces thermolilacinus IDWR81) were selected. The soil
      enzymes production potential of these isolates using soil extract and wheat straw
      under ssf was assessed. Utilization of soil extract as a fermentation medium for
      soil enzyme production by Actinomycetes has been reported first time in this
      study. Maximum chitinase (S. rochei IDWR19 12.2 U mg(-1) protein) and phytase
      activity (S. carpinensis IDWR53 5.2 U mg(-1) protein) was produced on 7th day of
      incubation, whereas maximum alkaline protease (S. rochei IDWR19 3.2 U mg(-1)
      protein) was produced on 6th day of incubation. For cellulase (S. rochei IDWR19
      7.4 U mg(-1) protein) and invertase (S. carpinensis IDWR53 451 U mg(-1) protein)
      maximum activity was observed on 4th as well as 5th day of incubation. On the
      basis of PGP activity and enzyme production, two actinomycete isolates (S. rochei
      IDWR19 and S. thermolilacinus IDRWR81) were selected for plant growth experiment.
      An increase of 12.2 and 24.5% in shoot length of plants inoculated with S. rochei
      IDWR19 and S. thermolilacinus IDWR81 was observed, respectively. A similar
      increase in biomass of 1.8- and 2.3-fold was also recorded for the two isolates,
      respectively. CONCLUSIONS: It could be concluded that Streptomyces sp. with high
      PGP activities and soil enzyme production capability significantly improved
      growth and development of wheat cv. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      abundant Actinomycetes obtained in this study (S. rochei IDWR19 and S.
      thermolilacinus IDWR81) are rhizosphere competent and effective strains.

PMID- 22849827
TI  - Multielemental determinations in chocolate drink powder using multivariate
      optimization and ICP OES.
AB  - In this work multivariate experiments were conducted to optimize the operating
      conditions for inductively coupled plasma optical emission spectrometry (ICP OES)
      for multielemental determinations in chocolate drink powder. The operating
      conditions were investigated using a 2(3) central composite design, where the
      variables studied were radio frequency power, nebulization flow rate, and
      auxiliary argon flow rate. The effects of these parameters on plasma robustness
      and on signal to background ratio (SBR) were considered in parallel, allowing the
      evaluation of robustness and detectability using few and fast experiments to
      select the best conditions for the determination of the analytes. In this case,
      the proposed experiments were applied to the optimization of a method aimed at
      the determination of Al, Ba, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Pb, V, and Zn
      in chocolate drink powder. The compromise conditions that allowed obtaining a
      robust and sensitive analytical method were radio frequency power of 1200 W,
      nebulization flow rate of 0.6 L/min, and auxiliary argon flow rate of 0.3 L/min.
      Using these conditions, recoveries between 95 and 105% and relative standard
      deviations lower than 5% were obtained for the majority of the analytes. The
      proposed method was successfully applied to the analysis of 15 samples of
      chocolate drink powder. The highest concentrations of metallic species were found
      in diet and light products.

PMID- 22849828
TI  - Monodisperse w/w/w double emulsion induced by phase separation.
AB  - We develop an approach to fabricate monodisperse water-in-water-in-water (w/w/w)
      double emulsion in microfluidic devices. A jet of aqueous solution containing two
      incompatible solutes, dextran and polyethylene glycol (PEG), is periodically
      perturbed into water-in-water (w/w) droplets. By extracting water out of the w/w
      droplet, the solute concentrations in the droplet phase increase; when the
      concentrations exceed the miscibility limit, the droplet phase separates into two
      immiscible phases. Consequently, PEG-rich droplets are formed within the single
      emulsion templates. These PEG-rich droplets subsequently coalesce with each
      other, resulting in transiently stable w/w/w double emulsions with a high degree
      of size uniformity. These double emulsions are free of organic solvents and thus
      are ideal for use as droplet-vessels in protein purification, as microreactors
      for biochemical reactions, and as templates for fabrication of biomaterials.

PMID- 22849826
TI  - Activation of PAR(2)  receptors sensitizes primary afferents and causes leukocyte
      rolling and adherence in the rat knee joint.
AB  - BACKGROUND AND PURPOSE: The PAR(2) receptors are involved in chronic arthritis by
      mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the
      rat knee joint. EXPERIMENTAL APPROACH: PAR(2) in rat knee joint dorsal root
      ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were
      demonstrated immunohistochemically. Electrophysiological recordings from knee
      joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of
      stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1
      100 nmol.100 MUL(-1) , via close intra-arterial injection). Fibre firing rate was
      recorded during joint rotations before and 15 min after administration of PAR(2)
      activating peptide or control peptide. Leukocyte kinetics in the synovial
      vasculature upon PAR(2) activation were followed by intravital microscopy for 60
      min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for
      transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) )
      receptors in the PAR(2) responses were assessed using the selective antagonists,
      SB366791 and RP67580 respectively. KEY RESULTS: PAR(2) were expressed in 59 +/-
      5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre
      firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 +/-
      43%, noxious; 90 +/- 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased
      leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre
      treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2)
      alone). CONCLUSIONS AND IMPLICATIONS: PAR(2) receptors play an acute inflammatory
      role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both
      PAR(2) -mediated neuronal sensitization and leukocyte trafficking.

PMID- 22849829
TI  - Environmental microbiology through the lens of high-throughput DNA sequencing:
      synopsis of current platforms and bioinformatics approaches.
AB  - The incursion of High-Throughput Sequencing (HTS) in environmental microbiology
      brings unique opportunities and challenges. HTS now allows a high-resolution
      exploration of the vast taxonomic and metabolic diversity present in the
      microbial world, which can provide an exceptional insight on global ecosystem
      functioning, ecological processes and evolution. This exploration has also
      economic potential, as we will have access to the evolutionary innovation present
      in microbial metabolisms, which could be used for biotechnological development.
      HTS is also challenging the research community, and the current bottleneck is
      present in the data analysis side. At the moment, researchers are in a sequence
      data deluge, with sequencing throughput advancing faster than the computer power
      needed for data analysis. However, new tools and approaches are being developed
      constantly and the whole process could be depicted as a fast co-evolution between
      sequencing technology, informatics and microbiologists. In this work, we examine
      the most popular and recently commercialized HTS platforms as well as
      bioinformatics methods for data handling and analysis used in microbial
      metagenomics. This non-exhaustive review is intended to serve as a broad state-of
      the-art guide to researchers expanding into this rapidly evolving field.

PMID- 22849830
TI  - Microbial 16S rRNA Ion Tag and community metagenome sequencing using the Ion
      Torrent (PGM) Platform.
AB  - Here we demonstrate a cost effective and scalable microbial ecology sequencing
      platform using the Ion Torrent Personal Genome Machine (PGM). We assessed both
      PCR amplified 16S rRNA and shotgun metagenomic approaches and generated 100,000+
      to 1,000,000+ reads using 'post-light' based sequencing technology within
      different sized semi-conductor chips. Further development of Golay barcoded Ion
      Tags allowed multiplex analyses of microbial communities with substantially
      reduced costs compared with platforms such as 454/GS-FLX. Using these protocols
      we assessed the bacterial and archaeal dynamics within covered anaerobic
      digesters used to treat piggery wastes. Analysis of these sequence data showed
      that these novel methanogenic waste treatment systems are dominated by bacterial
      taxa, in particular Clostridium, Synergistia and Bacteroides that were maintained
      as a stable community over extended time periods. Archaeal community dynamics
      were more stochastic with the key methanogenic taxa more difficult to resolve,
      principally due to the poor congruence seen between community structures
      generated either by nested PCR or metagenomic approaches for archaeal analyses.
      Our results show that for microbial community structure and function analyses,
      the PGM platform provides a low cost, scalable and high throughput solution for
      both Tag sequencing and metagenomic analyses.

PMID- 22849831
TI  - Loop-mediated isothermal amplification (LAMP) method based on two species
      specific primer sets for the rapid identification of Chinese Babesia bovis and B.
      bigemina.
AB  - Bovine babesiosis is a tick-transmitted hemoprotozoan disease that is mainly
      caused by Babesia bovis and/or Babesia bigemina and is characterized by
      significant morbidity and mortality worldwide. This disease is widespread in most
      parts of China. However, it is difficult to rapidly discriminate between the B.
      bovis and B. bigemina species. To detect and distinguish these species, a loop
      mediated isothermal amplification (LAMP) platform that targets specific sequences
      of the internal transcribed spacer (ITS) genes was developed. Specificity testing
      revealed that there was no cross-reaction with the other tick-borne parasites B.
      ovate, B. major, unnamed bovine Babesia, Theileria annulata, Theileria sinensis,
      Theileria sergenti, and Anaplasma marginale, or with bovine white blood cells.
      The sensitivity of the LAMP method was 0.1 pg DNA for both B. bovis and B.
      bigemina, which was superior to that of the classical PCR methods. This assay was
      evaluated for its diagnostic utility using blood samples collected from
      experimentally and naturally infected cattle in China. These findings indicate
      that the Babesia species-specific LAMP assay may have potential clinical
      application in the detection and differentiation of Babesia species, particularly
      in countries in which babesiosis is endemic.

PMID- 22849833
TI  - Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes.
AB  - Foregoing researches made on the N/OFQ system brought up a possible role for this
      system in cardiovascular regulation. In this study we examined how N/OFQ levels
      of the blood plasma changed in acute cardiovascular diseases. Three cardiac
      patient groups were created: enzyme positive acute coronary syndrome (EPACS, n =
      10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11).
      We compared the patients to healthy control subjects (n = 31). We found
      significantly lower N/OFQ levels in the EPACS [6.86 (6.21-7.38) pg/ml], ENACS
      [6.97 (6.87-7.01) pg/ml and IHD groups [7.58 (7.23-8.20) pg/ml] compared to the
      control group [8.86 (7.27-9.83) pg/ml]. A significant correlation was detected
      between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine
      kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in
      the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of
      acute cardiovascular disease, and the severity of symptoms has a significant
      negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ
      depression is in association with the level of ischemic stress and the following
      inflammatory response. Further investigations are needed to clarify the relevance
      and elucidate the exact effects of the ischemic stress on the N/OFQ system.

PMID- 22849834
TI  - Comparison of two depth of anaesthesia monitors during general anaesthesia:
      electrophysiological and clinical assessment.
AB  - Cerebral state monitor (CSM) is a recently developed anaesthesia depth monitor
      based on EEG measurement. Medline search confirmed that the accuracy of this
      monitor has already been compared with BIS monitoring; however, we did not find
      any studies comparing CSM monitor with AEP monitoring. Therefore, the aim of our
      study was to investigate the correlation between AAI using AEP monitor and CSI
      (cerebral state index) using CSM monitor. METHODS: Prospective, observational
      study involving 39 ASA I-III patients undergoing lumbar discuss hernia operation.
      Simultaneous registration of CSI and AAI was performed during general
      anaesthesia. The identical values were off-line analysed. Additionally in 20
      patients parallel registration of CSI and AAI was undertaken while anaesthesia
      was guided based on routine clinical signs. RESULTS: While analysing the data in
      the superficial, ideal and deep anaesthesia zones, we found that a relationship
      between CSI and AAI is weak. Our patients spent roughly the half of the clinical
      anaesthesia in the ideal zone based on the AAI index and less than 50% based on
      CSI. Almost one fifth of clinical anaesthesia based on AAI and nearly 40% based
      on CSI was spent in the deep anaesthesia zones. A superficial anaesthesia has
      been detected in 27% of time based on AAI and 17% based on CSI. CONCLUSIONS: CSI
      and AAI weakly correlated to each other. Depth of anaesthesia monitors may be
      useful in detecting patients who spend valuable time within the deep anaesthetic
      zone.

PMID- 22849835
TI  - Haemodynamic parameters and cognitive function during modeled acute volume loss.
AB  - PURPOSE: The purpose of the present study was to find a noninvasive way of
      detecting even smaller volume loss which is easier to carry out and possibly more
      precise than the currently used (mostly sphygmomanometer-based) methods.
      Haemodynamic and EEG measurements were carried out in simulated volume loss,
      involving blood donation and orthostatic challenges to assess adaptive responses
      and cognitive performance. Cognitive performance was assessed in an oddball task
      and changes of the evoked potential P300 were analyzed. Both haemodynamic and
      cognitive parameters were recorded in 'pre-donation' and 'post-donation'
      conditions for purposes of comparison. RESULTS: Cognitive performance (as
      reflected by P300 changes) was found to be a poor marker of volume loss.
      Difference between the two conditions in none of the parameters reached the level
      of statistical significance (defined as p < 0.05) RR mean, baroreceptor
      sensitivity and pulse pressure were rather sensitive to the relatively mild
      volume loss (p < 0.01 between pre- and post-conditions). CONCLUSION: Our study
      indicates that traditional sphygmomanometer based values can safely be replaced
      by values yielded by finger plethysmography, combined with brief orthostatic
      challenges and that P300 as a cognitive marker cannot be used to assess volume
      loss.

PMID- 22849836
TI  - Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in
      adult rats.
AB  - Prenatal irradiation is known to have aversive effects on the brain development,
      manifested in changes in some behavioural parameters in adult individuals. The
      aim of our work was to assess the effect of prenatal irradiation on different
      forms of behaviour and on hippocampal neurogenesis in rats. Pregnant female rats
      were irradiated with a dose of 1 Gy of gamma rays on the 16th day of gravidity.
      The progeny of irradiated and control animals aged 3 months were tested in Morris
      water maze (MWM), open field (OF) and in elevated plus maze test (PM). The
      prenatal irradiation negatively influenced the short-term spatial memory in MWM
      in female rats, although the long-term memory was not impaired. A statistically
      significant increase of basic locomotor activity in OF was observed in irradiated
      rats. The comfort behaviour was not altered. The results of PM showed an increase
      of anxiety in irradiated females. The level of hippocampal neurogenesis, assessed
      as the number of cells labelled with 5-bromo-2-deoxyuridine in the area of gyrus
      dentatus, was not statistically different in irradiated rats. Our results
      indicate, that prenatal irradiation with a low dose of gamma-rays can affect some
      innate and learned forms of behaviour in adult rats. We did not confirm a
      relation of behavioural changes to the changes of hippocampal neurogenesis.

PMID- 22849837
TI  - The sedative effects of hops (Humulus lupulus), a component of beer, on the
      activity/rest rhythm.
AB  - The hop (Humulus lupulus), a component of beer, is a sedative plant whose
      pharmacological activity is due principally to its bitter resins, especially to
      the alpha-acid component 2-methyl-3-buten-2-ol. The mechanism of action of the
      resin of hop consists of increasing the activity of the neurotransmitter gamma
      aminobutyric (GABA), inhibiting the central nervous system (CNS). OBJECTIVES: To
      analyze in an experimental model of diurnal animal the sedative effect of hop, a
      component of beer, on the activity/rest rhythm. METHODS: Experiments were
      performed with common quail (Coturnix coturnix) similar to humans in the sleep
      wake rhythm, isolated in 25 * 25 * 25 cm methacrylate cages, with food and water
      ad libitum, in a room with artificial ventilation (22 +/- 1  degrees C) and a
      lighting cycle of 12L/12D (n = 5). The doses administered, close to the content
      of non-alcoholic beer, were 1, 2 and 11 mg extract of hop as one capsule per day,
      at 18:00 h for one week. A control group received capsules only with a
      methylcellulose excipient and a basal group received no treatment. The
      chronobiological analysis of the animals' activity captured and logged by the
      software DAS24 was performed using the Ritme computer program (cosinor methods).
      RESULTS: With the dose of 2 mg, there was a statistically significant (p < 0.05)
      reduction of the arithmetic mean nocturnal activity (23 +/- 3.0) with respect to
      the basal (38.56 +/- 2.79), control (38.1 +/- 2.8) and other doses groups 1 mg
      (52.04 +/- 3.65) and 11 mg (47.47 +/- 5.88). This dose of 2 mg, similar to the
      concentration in beer, was more effective in reducing nocturnal activity than the
      other doses of 1 and 11 mg, as well as preserving the circadian activity/rest
      rhythm. CONCLUSION: The concentration of 2 mg of hop extract effectively
      decreased nocturnal activity in the circadian activity rhythm. On the basis of
      this investigation, administration of non-alcoholic beer would be recommended due
      to its hop content and consequent sedative action, which would be an aid to
      nocturnal sleep.

PMID- 22849838
TI  - Tianeptine's effects on spontaneous and Ca2+-induced uterine smooth muscle
      contraction.
AB  - Tianeptine is a novel anti-depressant with an efficacy equivalent to that of
      classical anti-depressants. Additional beneficial effects include
      neuroprotection, anti-stress and anti-ulcer properties whose molecular mechanisms
      are still not completely understood but may involve changes in the anti-oxidant
      defence system. Herein, we have studied the effects of tianeptine on both
      contractile activity of isolated rat uteri and components of the endogenous anti
      oxidative defence system. Tianeptine-induced dose-dependent inhibition of both
      spontaneous and Ca2+-induced contraction of uterine smooth muscle. The effect was
      more pronounced in the latter. Tianeptine treatment increased glutathione
      peroxidase (GSH-Px) and catalase (CAT) activities in spontaneous and Ca2+
      stimulated uteri. A significant decrease in glutathione-reductase (GR) activity
      in both spontaneous and Ca2+-induced uterine contractions after tianeptine
      treatment indicated a reduction in reduced glutathione and consequently a shift
      toward a more oxidised state in the treated uteri. In spontaneously contracting
      uteri, tianeptine caused a decrease in copper-zinc SOD (CuZnSOD) activity.
      Tianeptine's anti-depressant effects may be accomplished by triggering a cascade
      of cellular adaptations including inhibition of smooth muscle contractility and
      an adequate anti-oxidative protection response.

PMID- 22849839
TI  - Characterization of the autonomic innervation of mammary gland in lactating rats
      studied by retrograde transynaptic virus labeling and immunohistochemistry.
AB  - The aim of experiments was to characterize the neurons of the autonomic chain
      that innervates the nipple and the mammary gland of lactating rats using
      retrograde transynaptic virus labeling and neurotransmitter and neuropeptide
      immunohistochemistry. Two days after injection of green fluorescence protein
      labeled virus in two nipples and underlying mammary glands, labeling was observed
      in the ipsilateral paravertebral sympathetic trunk and the lateral horn. Three
      days after inoculation the labeling appeared in the brain stem and the
      hypothalamic paraventricular nucleus. Above the spinal cord the labeling was
      bilateral. A subpopulation of virus labeled cells in the paraventricular nuclei
      synthesized oxytocin. Labeled neurons in the lateral horn showed cholinergic
      immunoreactivity. These cholinergic neurons innervated the paravertebral ganglia
      where the virus labeled neurons were partially noradrenergic. The noradrenergic
      fibers in the mammary gland innervate the smooth muscle wall of vessels, but not
      the mammary gland in rats. The neurons in the lateral horn receive afferents from
      the brain stem, and paraventricular nucleus and these afferents are noradrenergic
      and oxytocinergic. New findings in our work: Some oxytocinergic fibers may
      descend to the neurons of the lateral horn which innervate noradrenergic neurons
      in the paravertebral sympathetic trunk, and in turn these noradrenergic neurons
      reach the vessels of the mammary gland.

PMID- 22849840
TI  - Characteristics of glucocorticoid synthesis-related factors in the adrenals of
      obese Zucker rats (short communication).
AB  - To understand the molecular mechanism of hyperglucocorticoidism in obese Zucker
      rats, this study investigated glucocorticoid synthesis-related factors and their
      transcription factors in the adrenals. glucocorticoid synthesis-related factors
      and their transcription factors in the adrenals. The serum corticosterone level
      after foot shock stress was higher in obese Zucker rats than in lean Zucker rats.
      after foot shock stress was higher in obese Zucker rats than in lean Zucker rats.
      In the adrenals from obese Zucker rats, the mRNA and protein levels of
      steroidogenic acute regulatory protein were higher than those from lean Zucker
      rats. rats. However, the mRNA level of steroidogenic factor-1(SF-1), an important
      transcription factor for these glucocorticoid synthesis-related factors, did not
      differ between lean and obese Zucker rats. glucocorticoid synthesis-related
      factors, did not differ between lean and obese Zucker rats. Focusing on leptin
      signal transduction, Akt phosphorylation, which was known to inhibit
      glucocorticoid secretion, decreased in the adrenals from obese Zucker rats. from
      obese Zucker rats. We found that the stress-induced glucocorticoid secretion and
      the glucocorticoid synthesis related factors in the adrenals were increased in
      obese Zucker rats. factors in the adrenals were increased in obese Zucker rats.
      The decrease of Akt phosphorylation in the adrenals might induce these increases
      in obese Zucker rats.adrenals might induce these increases in obese Zucker rats.

PMID- 22849841
TI  - Anorexic effect of peripheral cholecystokinin (CCK) varies with age and body
      composition (short communication).
AB  - Obesity of middle-aged mammals is followed at old age by anorexia and cachexia
      leading to sarcopenia. Complex age- and body composition-related alterations in
      the regulation of energy homeostasis may be assumed in the background. We aimed
      to test the possible contribution of age- and body composition-related changes of
      satiety responses to catabolic brain-gut-axis peptide cholecystokinin (CCK) to
      these alterations in energy balance during aging. Male Wistar rats (6-8
      animals/group) aged 2 months (juvenile), 3 months (young adult), 6 or 12 months
      (early or late middle-aged), and 24 months (old) were injected intraperitoneally
      with 5 MUg CCK-8 prior to re-feeding after 48-h food-deprivation. CCK suppressed
      re-feeding in young adult (26.8%), early middle-aged (35.5%), and old (31.4%)
      animals, but not in juvenile or late middle-aged rats (one-way ANOVA). CCK
      resistance of 12 months old rats was prevented by life-long calorie-restriction:
      CCK suppressed their re-feeding by 46.8%. Conversely, in highfat diet-induced
      obese 6 months old rats CCK failed to suppress re-feeding. In conclusion, age
      related changes in satiety responsiveness to CCK may contribute to the age
      related obesity of middle-aged as well as to the anorexia of old animals. CCK
      responsiveness is also influenced by body composition: calorie-restriction
      prevents the resistance to CCK, pre-existing obesity enhances it.

PMID- 22849842
TI  - In vitro suppression of lymphocyte activation in patients with seasonal allergic
      rhinitis and pollen-related asthma by cetirizine or azelastine in combination
      with ginkgolide B or astaxanthin.
AB  - Novel strategies are evaluated for management of allergic rhinitis and asthma in
      patients co-afflicted with both disorders. It is hypothesized that the platelet
      activating factor receptor antagonist ginkgolide B (GB) and the carotenoid
      antioxidant astaxanthin (ASX) interact with antihistamines cetirizine
      dihydrochloride (CTZ) and azelastine (AZE) to potentiate their ability to
      downregulate potentially pathological immune activation. Peripheral blood
      mononuclear cells from asthmatics and healthy subjects, cultured 24 hours with 50
      MUg/ml phytohemaglutinin (PHA) or PHA plus each drug are analyzed by flow
      cytometry for expression of CD25+ or HLA-DR+ by CD3+ (T cells). Results are
      reported as stimulation indices for CD3+CD25+ (SICD3+CD25+) and CD3+HLA-DR+
      (SICD3+HLADR+) cells in cultures treated with PHA alone, versus cultures treated
      with both PHA and drugs. Optimal suppression of activated cells was observed in
      cultures stimulated with ASX 10-6 M + CTZ 10-6 M (SICD3+CD25+, p = 0.016;
      SICD3+HLADR, p = 0.012); ASX 10-6 M + AZE 10-6 M (SICD3+CD25+, p = 0.012;
      SICD3+HLADR, p = 0.015); GB 10-6 M + CTZ 10-6 M (SICD3+CD25+, p = 0.024,
      SICD3+HLADR+, p = 0.019). Results demonstrate improved activity of antihistamines
      by 2 phytochemicals, suggesting dosing strategies for animal trials of ASX- or GB
      augmented formulations for seasonal allergic rhinitis and asthma.

PMID- 22849843
TI  - Effects of humoral factors on ventilation kinetics during recovery after impulse
      like exercise.
AB  - To clarify the ventilatory kinetics during recovery after impulse-like exercise,
      subjects performed one impulse-like exercise test (one-impulse) and a five-times
      repeated impulse-like exercises test (five-impulse). Duration and intensity of
      the impulse-like exercise were 20 sec and 400 watts (80 rpm), respectively.
      Although blood pH during recovery (until 10 min) was significantly lower in the
      five-impulse test than in the one-impulse test, ventilation (.VE) in the two
      tests was similar except during the first 30 sec of recovery, in which it was
      higher in the five-impulse test. In one-impulse, blood CO2 pressure (PCO2) was
      significantly increased at 1 min during recovery and then returned to the pre
      exercise level at 5 min during recovery. In the five-impulse test, PCO2 at 1 min
      during recovery was similar to the pre-exercise level, and then it decreased to a
      level lower than the pre-exercise level at 5 min during recovery. Accordingly,
      PCO2 during recovery (until 30 min) was significantly lower in the five-impulse
      than in one-impulse test..VE and pH during recovery showed a curvilinear
      relationship, and at the same pH, ventilation was higher in the one-impulse test.
      These results suggest that ventilatory kinetics during recovery after impulse
      like exercise is attributed partly to pH, but the stimulatory effect of lower pH
      is diminished by the inhibitory effect of lower PCO2.

PMID- 22849844
TI  - Trunk position influences joint activation pattern and physical performance
      during vertical jumping.
AB  - Eight well-trained males carried out squat jump and countermovement jump with
      large (SJL and CMJL) and with small (SJS and CMJS) range of motion to study the
      influence of trunk position on joint recruitment pattern and jumping height. The
      main criteria in SJS and CMJS were to maintain trunk in near vertical position
      during execution. Joint angles, activation time, time at maximum joint velocity
      for ankle joint, knee joint and hip joint, vertical propulsion time and jumping
      height were determined using film analysis. The joint activation followed
      proximal to distal pattern in CMJL, SJL and CMJS, but the pattern was reversed in
      SJS. The ratio of active state and vertical propulsion time was similar for all
      joints (63.1 and 72.8%) in CMJL, SJL and CMJS except in SJS where the ratio was
      significantly less for hip (46.9%) and knee (51.9%). The difference between CMJL
      and SJL in jumping height was 6.9 +/- 2.8 cm which is significantly less than
      that between CMJS and SJS (14.5 +/- 5.3 cm). We concluded that knee joint and hip
      joint muscles could not contribute to the positive work during the push-off phase
      when the range of motion is small, the trunk is vertical and the activation level
      of the muscles is low.

PMID- 22849845
TI  - Post-transplant diabetes mellitus - risk factors and effects on the function and
      morphology of the allograft.
AB  - The incidence of post-transplant diabetes mellitus and its effects on the kidney
      allograft function and morphology were assessed. Patients were divided into three
      groups according to their glucose metabolism. Risk factors for diabetes were
      first assessed, and then changes in renal function were checked. Morphological
      changes in the allografts were examined by protocol biopsies. The overall
      incidence of diabetes was 16%. The development of diabetes was influenced
      significantly by the body mass index, the body weight and the age of the
      recipient. The incidence of diabetes was 8.6% in patients on cyclosporine A
      therapy and 28.8% in those on tacrolimus (p < 0.05). As to the morphology of the
      kidney, a significantly higher proportion of the biopsies showed severe
      interstitial fibrosis/tubular atrophy (p = 0.0004) and subclinical acute
      rejection ( p = 0.001) in the diabetic group compared to the normal one. This
      clinical study has revealed that the adverse effect of diabetes on the allograft
      can be detected with protocol biopsy before the manifestation of a functional
      deterioration.

PMID- 22849846
TI  - Factors influencing skin autofluorescence of patients with peritoneal dialysis.
AB  - Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess
      tissue advanced glycation end products (AGE). In patients with end-stage renal
      disease and in those on hemodialysis AGE production is increased. Less is known
      about those treated with peritoneal dialysis (PD). In this study we tested if SAF
      is influenced by clinical and treatment characteristics in PD patients.This cross
      sectional study included 198 PD patients (of those, 128 were on traditional
      glucose-based solutions and 70 patients were partially switched to icodextrin
      based PD). SAF measurements were done with a specific AGE Reader device. The
      impact of patients' age, gender, current diabetes, duration of PD, cumulative
      glucose exposure, body mass index, smoking habits and use of icodextrin on SAF
      values were tested with multiple regression analysis.Our analysis revealed that
      patients' age, current diabetes and icodextrin use significantly increase
      patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD
      patients with diabetes and on icodextrin solution is increased. Further
      investigation is required whether this finding is due to the icodextrin itself or
      for a still unspecified clinical characteristic of PD population treated with
      icodextrin.

PMID- 22849847
TI  - Compromised bone healing following spacer removal in a rat femoral defect model.
AB  - PURPOSE: The clinical demand for bone grafting materials necessitated the
      development of animal models. Critical size defect model has been criticized
      recently, mainly for its inaccuracy. Our objective was to develop a dependable
      animal model that would provide compromised bone healing, and would allow the
      investigation of bone substitutes. METHODS: In the first group a critical size
      defect was created in the femur of adult male Wistar rats, and a non-critical
      defect in the remaining animals (Groups II, III and IV). The defect was left
      empty in group II, while in groups III and IV a spacer was interposed into the
      gap. Osteoblast activity was evaluated by NanoSPECT/CT imaging system. New bone
      formation and assessment of a union or non-union was observed by MUCT and
      histology. RESULTS: The interposition model proved to be highly reproducible and
      provided a bone defect with compromised bone healing. Significant bone
      regeneration processes were observed four weeks after removal of the spacer.
      CONCLUSION: Our results have shown that when early bone healing is inhibited by
      the physical interposition of a spacer, the regeneration process is compromised
      for a further 4 weeks and results in a bone defect during the time-course of the
      study.

PMID- 22849849
TI  - A long-term predictive validity study: can the CDI Short Form be used to predict
      language and early literacy skills four years later?
AB  - This longitudinal study examined the predictive validity of the MacArthur
      Communicative Developmental Inventories-Short Form (CDI-SF), a parent report
      questionnaire about children's language development (Fenson, Pethick, Renda, Cox,
      Dale & Reznick, 2000). Data were first gathered from parents on the CDI-SF
      vocabulary scores for seventy-six children (mean age=1 ; 10). Four years later
      (mean age=6 ; 1), children were assessed on language outcomes (expressive
      vocabulary, syntax, semantics and pragmatics) and code-related skills, including
      phonemic awareness, word recognition and decoding skills. Hierarchical regression
      analyses revealed that early expressive vocabulary accounted for 17% of the
      variance in picture vocabulary, 11% of the variance in syntax, and 7% of the
      variance in semantics, while not accounting for any variance in pragmatics in
      kindergarten. CDI-SF scores did not predict code-related skills in kindergarten.
      The importance of early vocabulary skills for later language development and CDI
      SF as a valuable research tool are discussed.

PMID- 22849851
TI  - Evaluation of mesoporous silicon thermal conductivity by electrothermal finite
      element simulation.
AB  - The aim of this work is to determine the thermal conductivity of mesoporous
      silicon (PoSi) by fitting the experimental results with simulated ones. The
      electrothermal response (resistance versus applied current) of differently
      designed test lines integrated onto PoSi/silicon substrates and the bulk were
      compared to the simulations. The PoSi thermal conductivity was the single
      parameter used to fit the experimental results. The obtained thermal conductivity
      values were compared with those determined from Raman scattering measurements,
      and a good agreement between both methods was found. This methodology can be used
      to easily determine the thermal conductivity value for various porous silicon
      morphologies.

PMID- 22849850
TI  - 25-Hydroxycholesterol enhances cytokine release and Toll-like receptor 3 response
      in airway epithelial cells.
AB  - BACKGROUND: 25-hydroxycholesterol (25-HC) is one of the oxysterols, which are
      oxidized derivatives of cholesterol, and has been reported to be involved in the
      pathogenesis of atherosclerosis and Alzheimer's disease. In lung, the possible
      involvement of 25-HC in airway diseases has been revealed. In the present study,
      we examined whether 25-HC affects the release of cytokines and also modulates the
      responses of toll-like receptor 3 (TLR3) in airway epithelial cells. METHODS: The
      effect of 25-HC on the release of cytokines from primary human bronchial
      epithelial cells after stimulation with or without polyinosine-polycytidylic acid
      [poly(I:C)], a ligand for TLR3, and the signal transduction were examined.
      RESULTS: 25-HC significantly potentiated the release of interleukin-8 (IL-8) and
      IL-6 from the cells. This effect was more potent compared with that of other
      oxysterols, 22-HC and 27-HC. GW3965 and TO901317, synthetic agonists of liver X
      receptors that are receptors for oxysterols, did not augment the IL-8 release. 25
      HC enhanced the nuclear factor-kappa B (NF-kappaB) DNA binding activity and
      translocation of phosphorylated c-Jun into the nucleus. The release of IL-8 was
      inhibited by the NF-kappaB inhibitor, caffeic acid phenethyl ester (CAPE), an
      inhibitor of nuclear factor kappa-B alpha (IkappaBalpha) inhibitor, BAY 11-7085,
      and an inhibitor of nuclear factor kappa-B kinase-2 (IKK-2) inhibitor, SC-514,
      but not by a c-Jun N-terminal kinase (JNK) inhibitory peptide, L-JNKi1. 25-HC
      significantly potentiated IL-8 release in poly(I:C)-treated cells and the
      augmentation was inhibited by CAPE, BAY 11-7085, and SC-514. Furthermore, 25-HC
      potentiated the translocation of interferon regulatory factor 3 into the nucleus
      and the release of interferon-beta (IFN-beta) in poly(I:C)-treated cells.
      CONCLUSIONS: These data demonstrated that 25-HC augments the release of IL-8 and
      IL-6 via NF-kappaB signalling pathway and enhances the release of IL-8 and IFN
      beta after stimulation of TLR3 in airway epithelial cells. 25-HC may be involved
      in the neutrophilic airway inflammation through the stimulant effect of IL-8 and
      IL-6 release and also potentiate the TLR3-mediated innate immunity in airway
      diseases.

PMID- 22849852
TI  - Fate of enterotoxigenic Staphylococcus aureus and staphylococcal enterotoxins in
      Feta and Galotyri cheeses.
AB  - In this study the fate of enterotoxigenic Staphylococcus aureus and
      staphylococcal enterotoxins in Feta and Galotyri cheeses were studied. Initially,
      the enterotoxigenic abilities of four Staph. aureus LHA, LHB, LHC and LHD strains
      isolated from raw ovine milk were examined in both BHI broth and ovine milk. In
      BHI broth, the Staph. aureus LHA, LHB, LHC and LHD strains were found toxigenic
      at 37  degrees C producing the staphylococcal enterotoxins (SEs) serotypes SEA,
      SEB, SEC and SED, respectively, whereas in ovine milk at 37  degrees C, Staph.
      aureus LHD was found to produce only SED, while no SE production was observed for
      the other examined strains. Thus, the fate of only Staph. aureus LHD and SED were
      examined in Feta and Galotyri cheeses. The cheeses were made from raw ovine toxic
      milk with preformed SED or raw ovine milk contaminated with high (ca 6 log
      cfu/ml) and low inocula (ca 3 log cfu/ml) of Staph. aureus LHD. Results showed
      that the pathogen was eliminated at slower rate in Galotyri cheese than in Feta
      cheese, for the high (5 d vs. 16 d) or the low (1 d vs. 12 d) inoculum trials. In
      both cheeses produced from the toxic milk, SED was detected during manufacturing
      and storage. SED was also detected in the curd (2 h), when Staph. aureus LHD
      populations had reached ca 7 log cfu/g, and up to the end of storage for the high
      inoculum trials of both cheeses. No SED was observed for the low inoculum trials
      of either cheese.

PMID- 22849853
TI  - Spatial variability in levels of benzene, formaldehyde, and total benzene,
      toluene, ethylbenzene and xylenes in New York City: a land-use regression study.
AB  - BACKGROUND: Hazardous air pollutant exposures are common in urban areas
      contributing to increased risk of cancer and other adverse health outcomes. While
      recent analyses indicate that New York City residents experience significantly
      higher cancer risks attributable to hazardous air pollutant exposures than the
      United States as a whole, limited data exist to assess intra-urban variability in
      air toxics exposures. METHODS: To assess intra-urban spatial variability in
      exposures to common hazardous air pollutants, street-level air sampling for
      volatile organic compounds and aldehydes was conducted at 70 sites throughout New
      York City during the spring of 2011. Land-use regression models were developed
      using a subset of 59 sites and validated against the remaining 11 sites to
      describe the relationship between concentrations of benzene, total BTEX (benzene,
      toluene, ethylbenzene, xylenes) and formaldehyde to indicators of local sources,
      adjusting for temporal variation. RESULTS: Total BTEX levels exhibited the most
      spatial variability, followed by benzene and formaldehyde (coefficient of
      variation of temporally adjusted measurements of 0.57, 0.35, 0.22, respectively).
      Total roadway length within 100 m, traffic signal density within 400 m of
      monitoring sites, and an indicator of temporal variation explained 65% of the
      total variability in benzene while 70% of the total variability in BTEX was
      accounted for by traffic signal density within 450 m, density of permitted
      solvent-use industries within 500 m, and an indicator of temporal variation.
      Measures of temporal variation, traffic signal density within 400 m, road length
      within 100 m, and interior building area within 100 m (indicator of heating fuel
      combustion) predicted 83% of the total variability of formaldehyde. The models
      built with the modeling subset were found to predict concentrations well,
      predicting 62% to 68% of monitored values at validation sites. CONCLUSIONS:
      Traffic and point source emissions cause substantial variation in street-level
      exposures to common toxic volatile organic compounds in New York City. Land-use
      regression models were successfully developed for benzene, formaldehyde, and
      total BTEX using spatial indicators of on-road vehicle emissions and emissions
      from stationary sources. These estimates will improve the understanding of health
      effects of individual pollutants in complex urban pollutant mixtures and inform
      local air quality improvement efforts that reduce disparities in exposure.

PMID- 22849854
TI  - Biomimetic semisynthesis of arglabin from parthenolide.
AB  - The semisynthesis of arglabin, an anticancer drug in clinical application, is
      developed from abundant natural product parthenolide via three steps. Each step
      in this sequence is highly stereoselective, and the substrate-dependent
      stereoselectivity in the epoxidation step can be explained by computational
      calculations. The success of chemical semisynthesis of arglabin suggests that the
      biosynthesis of arglabin might proceed in a similar pathway.

PMID- 22849855
TI  - Role of intervention for biliary and gastric/intestinal obstruction in gastric
      cancer with peritoneal metastasis.
AB  - BACKGROUND AND AIM: Gastrointestinal (GI) luminal obstruction or malignant
      biliary obstruction (MBO) is not a rare condition in gastric cancer patients with
      peritoneal metastasis. The role of endoscopic or percutaneous interventions is
      not fully elucidated in this setting. METHODS: A total of 123 patients with
      unresectable or recurrent gastric adenocarcinoma with peritoneal metastasis
      receiving intravenous and intraperitoneal paclitaxel combined with S-1 were
      retrospectively studied. Safety and efficacy of interventions for GI luminal
      obstruction and MBO were evaluated. RESULTS: A total of 27 patients (22%)
      underwent GI luminal and/or biliary interventions; GI luminal alone in 10,
      biliary alone in 10 and both in seven, with a technical success rate of 100%.
      Clinical success rate was 65% in self-expandable metallic stents (SEMS) placement
      for GI luminal obstruction. Eastern Cooperative Oncology Group (ECOG) performance
      status (PS) was prognostic of clinical success in GI luminal stenting (100% in PS
      of 1 vs 14% in PS of 2-3, P < 0.001). Biliary drainage (endoscopic SEMS placement
      in four and percutaneous transhepatic biliary drainage in 12) relieved
      obstructive jaundice in 94%. Six complications were observed: four after GI
      luminal stenting (two occlusion and one aspiration pneumonia) and two after
      biliary stenting (one cholangitis and one cholecystitis). Median survival after
      the initial intervention was 5.7 months. PS at interventions was prognostic of
      survival after interventions (12.3 months in PS of 1 vs 2.2 months in PS of 2 or
      3, P < 0.001). CONCLUSION: Endoscopic or percutaneous interventions for GI
      luminal obstruction or MBO were feasible and effective in gastric cancer patients
      with peritoneal dissemination receiving combination chemotherapy.

PMID- 22849856
TI  - Towards the use of non-psychoactive cannabinoids for prostate cancer.
AB  - The palliative effects of Cannabis sativa (marijuana), and its putative main
      active ingredient, Delta(9) -tetrahydrocannabinol (THC), which include appetite
      stimulation, attenuation of nausea and emesis associated with chemo- or
      radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer
      patients, are well-known. Because of the adverse psychoactive effects of THC,
      numerous recent preclinical studies have been focused on investigating other non
      psychoactive constituents of C. sativa, such as cannabidiol, for potential
      therapeutic use. In this issue of the British Journal of Pharmacology, De
      Petrocellis and colleagues present comprehensive evidence that plant-derived
      cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma
      viability in vitro. They also showed that the extract was active in vivo, either
      alone or when administered with drugs commonly used to treat prostate cancer (the
      anti-mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti-androgen
      bicalutamide (Casodex)) and explored the potential mechanisms behind these
      antineoplastic effects.

PMID- 22849858
TI  - Disseminated and circulating tumour cells and their role in breast cancer.
AB  - Metastatic spread of the primary tumour is responsible for the vast majority of
      cancer-related deaths. Detection of disseminated tumour cells in the bone marrow
      and circulating tumour cells in the peripheral blood is correlated with early
      metastatic relapse in breast cancer. Positive detection of disseminated tumour
      cells was associated with poor overall survival of patients. Current research has
      been focused on integrating minimal residual disease as a prognostic and
      predictive tool in the management of breast cancer. Detection of disseminated
      tumour cells/circulating tumour cells is not yet standardized in clinical
      practice because of using different enrichment and detection methods. Therefore,
      standardization of the used methods is necessary in the future. Previous achieved
      findings must be verified in larger prospective multicentre studies. Further
      characterization of disseminated tumour cells/circulating tumour cells will be
      essential for developing and monitoring the efficacy of new therapeutic concepts.
      The aim of this review was to provide a short survey of the metastatic cascade
      and cancer stem cell theory, and data on the molecular and functional
      characterization of disseminated tumour cells/circulating tumour cells. Finally,
      we discuss the potential clinical impact of disseminated tumour cells/circulating
      tumour cells and results of several recent studies.

PMID- 22849857
TI  - Phytochemical analysis and Enzyme Inhibition Assay of Aerva javanica for Ulcer.
AB  - BACKGROUND: Aerva javanica (Burm. f.) Juss. ex Schult. (Amaranthacea) is
      traditionally used for the treatment of wound healings, cough, diarrhoea, ulcer
      and hyperglycaemia. The current study was aimed to fractionate and isolate
      bioactive compounds and ultimately to evaluate their anti-ulcereogenic potential.
      RESULTS: In order to achieve these aims, the fractionation, purifications and
      then biological potential determination of the isolated compounds was carried
      out. For purification purpose, initially extraction of the plant material was
      done with aqueous MeOH in the order of increasing polarity by using solvent
      solvent extraction method. Phytochemical analysis revealed the presence of three
      compounds, 3-hydroxy-4 methoxybenzaldehyde (1), ursolic acid (2) and (E)-N-(4
      hydroxy-3-methoxyphenethyl)-3-(4-hydroxy-3-ethoxyphenyl) acryl amide (3).
      Inhibition of urease activity of various fractions revealed that ethyl acetate
      fraction showed significant activity (P <0.05) as compared to other fractions.
      (E)-N-(4-hydroxy-3-methoxyphenethyl)-3-(4-hydroxy-3-ethoxyphenyl) acryl amide (3)
      showed marked anti ulcer activity (P <0.05). CONCLUSION: These results suggested
      the mild potential of A. javanica against ulcer.

PMID- 22849859
TI  - Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor
      stimulates trans-differentiation of human non-endocrine pancreatic cells into
      insulin-producing cells.
AB  - Differentiation of pancreatic beta-cells is regulated by a wide range of
      signalling pathways. The aim of our current work was to evaluate the effect of
      the Jak/Stat signalling pathway on the differentiation of human non-endocrine
      pancreatic cells into insulin-producing cells. Activation of the Jak/Stat
      signalling pathway by leukaemia inhibitory factor (LIF) stimulated
      differentiation of C-peptide-negative human non-endocrine pancreatic cells into
      insulin-producing cells in 6.3 +/- 2.0 % cells (N = 5) and induced expression of
      pro-endocrine transcription factor neurogenin 3, Notch signalling pathway
      suppressor HES6 and stimulator of beta-cell neogenesis REG3A. The expression of
      the REG3A gene and increased rate of differentiation into insulin-producing cells
      (10.2 +/- 2.1 %) were further stimulated by a combination of LIF with
      nicotinamide and dexamethasone. Glucose-stimulated (5 vs. 20 mM) C-peptide
      secretion confirmed proper insulin secretory function of trans-differentiated
      insulin-producing cells (0.51 vs. 2.03 pmol C-peptide/MUg DNA, P < 0.05). Our
      results indicate that Jak/Stat signalling critically contributes to trans
      differentiation of non-endocrine pancreatic cells into functional insulin
      producing cells. The positive effect of the Jak/Stat signalling pathway on trans
      differentiation is mediated by the key genes that activate differentiation of
      pancreatic beta-cells.

PMID- 22849860
TI  - Xenogeneic protein-free cultivation of mesenchymal stromal cells - towards
      clinical applications.
AB  - We have studied a rapid cultivation method for human mesenchymal stromal cells
      based on CellGroTM medium and human serum, supplemented with insulin, ascorbic
      acid, dexamethasone, epidermal growth factor, platelet-derived growth factor BB,
      macrophage colony-stimulating factor and fibroblast growth factor 2. This study
      has shown that rapid expansion of human multipotent mesenchymal stromal cells
      using human serum could not be achieved without addition of growth factors.
      Furthermore, we have found that insulin and, quite probably, epidermal growth
      factor may be omitted from our formula without loss of colony-forming capacity or
      total cell yield. On the other hand, dexamethasone, ascorbic acid and fibroblast
      growth factor 2 were necessary for the growth and colony-forming capacity of
      multipotent mesenchymal stromal cells, while platelet-derived growth factor BB
      prevented their differentiation into adipogenic lineage. Moreover, multipotent
      mesenchymal stromal cells cultivated in our system expressed higher levels of
      bone morphogenetic protein 2, but not bone morphogenetic protein 7, than cells
      cultivated in alpha-MEM with foetal bovine serum. This shows that our system
      promotes differentiation of mesenchymal cells towards osteogenic and chondrogenic
      lineages, making them more suitable for bone and cartilage engineering than cells
      grown in conventional media. Furthermore, we have proved that these cells may be
      conveniently cultivated in a closed system, in vessels certified for clinical use
      (RoboFlaskTM), making the transfer of our cultivation technology to good clinical
      practice easier and more convenient.

PMID- 22849861
TI  - Expression of Wnt 3a, beta-catenin, cyclin D1 and PCNA in mouse dentate gyrus
      subgranular zone (SGZ): a possible role of Wnt pathway in SGZ neural stem cell
      proliferation.
AB  - In mammalian dentate gyrus subgranular zone, the addition of new neurons
      throughout adulthood is a remarkable form of structural plasticity. Yet, the
      molecular controls over subgranular zone neural stem cell proliferation,
      survival, and differentiation are poorly understood. In this study we analysed
      the expression of Wnt 3a, beta-catenin, cyclin D1 and proliferating cell nuclear
      antigen in mouse subgranular zone to elucidate the involvement of Wnt pathway in
      subgranular zone neural stem cell proliferation. We performed
      immunohistochemistry and RT-PCR for the above molecules on adult and postnatal
      developing hippocampal tissues of mice, respectively. RT-PCR analysis showed a
      gradual increase in expression of mRNA of Wnt 3a, beta-catenin, cyclin D1 and
      proliferating cell nuclear antigen as the postnatal hippocampus developed, and
      immunohistochemical analysis showed a highly positive immunoreactive expression
      for Wnt 3a, beta-catenin, cyclin D1 and proliferating cell nuclear antigen in the
      subgranular zone cells. Together, our data suggested that the Wnt pathway is
      activated in subgranular zone and could play an important role in regulating
      subgranular zone neural stem cell proliferation in mouse hippocampus.

PMID- 22849862
TI  - Genetic and functional analyses of MRAS and HNF1A genes in diabetes and diabetic
      nephropathy.
AB  - Evidence has recently indicated that the MRAS and HNF1A genetic polymorphisms are
      associated with coronary artery disease. The MRAS and HNF1A genes are located on
      chromosomes 3q and 12q within the regions where associations with diabetes and
      diabetic nephropathy occur. We thus performed genetic and functional analyses of
      these two genes to evaluate their impacts on diabetes and diabetic nephropathy.
      MRAS and HNF1A genetic polymorphisms were genotyped in 1399 Czech subjects
      including non-diabetic controls (339), type 1 (243) and type 2 (817) diabetic
      patients with and without diabetic nephropathy using TaqMan allelic
      discrimination. Gene expression levels in the kidneys of diabetic Goto-Kakizaki
      and Wistar rats were detected with real-time RT-PCR. Despite no significance in
      genetic analysis of diabetic subjects, SNP rs2259816 in the HNF1A gene tended to
      associate with diabetic nephropathy in type 1 diabetic patients. The hnf1a gene
      expression was significantly decreased in kidney tissues of Goto-Kakizaki rats
      compared to Wistar and insulin-treated Goto-Kakizaki rats. There was neither
      significant association in the MRAS genetic polymorphism with diabetic
      nephropathy nor variation of mras gene expression in the kidneys of Goto-Kakizaki
      and Wistar rats. Data from the present study have not proved any significant
      association of the MRAS and HNF1A genetic polymorphisms with diabetes and
      diabetic nephropathy in a cohort of Czech population. However, the functional
      analysis and the trend in genetic analysis suggest that the HNF1A gene may have
      primary genetic impact on the development of diabetic nephropathy.

PMID- 22849863
TI  - Limitations of macroscopic fluorescence imaging for the estimation of tumour
      growth in an orthotopic glioma mouse model.
AB  - Imaging methods based on light detection are being increasingly used for the non
      invasive assessment of tumour growth in animal models. In contrast with
      bioluminescence imaging, there are no studies assessing the use of macroscopic
      fluorescence imaging for the longitudinal monitoring of tumour growth in an
      orthotopic glioma mouse model. Glioma cells expressing the red-shifted
      fluorescent protein mKate2 were orthotopically implanted to NOD-rag mice and the
      tumour size estimated by macroscopic fluorescence imaging was compared to the
      tumour volume determined morphometrically. There was no significant correlation
      between the data obtained by non-invasive macroscopic fluorescence imaging and
      post mortem morphometry. In addition, the fluorescence imaging failed to detect a
      morphometrically verified difference in tumour volume between animals with
      tumours expressing a potential tumour suppressor gene and controls. The
      fluorescence signal was affected by the spatial pattern of tumour growth and
      substantially attenuated by the interfering brain tissue. Our results indicate
      that the fluorescence signal emitted by glioma cells reflected not only the
      tumour mass, but also its spatial distribution. Macroscopic planar FLI in an epi
      illumination mode and a conventional source of excitation light therefore appears
      to be more suitable for semi-quantitative assessment of the tumour growth
      especially in the case of superficially located tumours rather than for precise
      volume estimation of the xenografts located deep within the brain tissue.

PMID- 22849864
TI  - Computational study of adsorption and separation of CO2, CH4, and N2 by an rht
      type metal-organic framework.
AB  - In this work, a computational study is performed to evaluate the adsorption-based
      separation of CO(2) from flue gas (mixtures of CO(2) and N(2)) and natural gas
      (mixtures of CO(2) and CH(4)) using microporous metal organic framework Cu-TDPAT
      as a sorbent material. The results show that electrostatic interactions can
      greatly enhance the separation efficiency of this MOF for gas mixtures of
      different components. Furthermore, the study also suggests that Cu-TDPAT is a
      promising material for the separation of CO(2) from N(2) and CH(4), and its
      macroscopic separation behavior can be elucidated on a molecular level to give
      insight into the underlying mechanisms. On the basis of the single-component
      CO(2), N(2), and CH(4) isotherms, binary mixture adsorption (CO(2)/N(2) and
      CO(2)/CH(4)) and ternary mixture adsorption (CO(2)/N(2)/CH(4)) were predicted
      using the ideal adsorbed solution theory (IAST). The effect of H(2)O vapor on the
      CO(2) adsorption selectivity and capacity was also examined. The applicability of
      IAST to this system was validated by performing GCMC simulations for both single
      component and mixture adsorption processes.

PMID- 22849865
TI  - Human foreskin fibroblast produces interleukin-6 to support derivation and self
      renewal of mouse embryonic stem cells.
AB  - INTRODUCTION: Embryonic stem cells (ESCs) provide an attractive cell source for
      basic research and disease treatment. Currently, the common culture system for
      mouse ESC requires mouse embryonic fibroblast (MEF) as a feeder layer
      supplemented with leukemia inhibitory factor (LIF). The drawbacks associated with
      MEF and the cost of LIF have motivated exploration of new feeder cell types to
      maintain self-renewal of mouse ESCs without the need of exogenous LIF. However,
      why these feeder cells could maintain ESCs at the undifferentiated state
      independent of exogenous LIF is unclear. METHODS: We derived mouse ESC lines
      using human foreskin fibroblast (HFF) in the absence of exogenous LIF. We also
      examined the dependence of HFF on the JAK-Stat3 pathway to maintain ESC
      identities and explored the potential molecular basis for HFF to support self
      renewal of ESCs. RESULTS: HFF supported mouse ESC self-renewal superiorly to
      MEFs. Using the HFF system, multiple lines of mouse ESCs were successfully
      derived without addition of exogenous LIF and any small molecular inhibitors.
      These ESCs had capacities to self-renew for a long period of time and to
      differentiate into various cell types of the three germ layers both in vitro and
      in vivo. Moreover, the ESCs participated in embryonic development and contributed
      to germ cell lineages in the chimeric mouse. At a molecular level, HFF was
      dependent on the JAK-Stat3 pathway to maintain ESC self-renewal. The high level
      of interleukin-6 (IL-6) produced by HFF might be responsible for the exogenous
      LIF-independent effect. CONCLUSION: This study describes an efficient, convenient
      and economic system to establish and maintain mouse ESC lines, and provides
      insights into the functional difference in the support of ESC culture between MEF
      and HFF.

PMID- 22849866
TI  - Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced
      down-regulation of HSP70 and EGFR.
AB  - Curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are
      major forms of curcuminoids found in the rhizomes of turmeric. This study
      examined the effects of three curcuminoid analogues on prostate cancer cells. The
      results revealed that DMC demonstrated the most efficient cytotoxic effects on
      prostate cancer PC3 cells. DMC activated AMPK and in turn decreased the activity
      and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and
      acetyl-CoA carboxylase (ACC). AICAR, an AMPK activator, and DMC down-regulated
      heat shock protein (HSP) 70 and increased the activity of the pro-apoptotic
      effector, caspase-3. In addition, DMC sustained epidermal growth factor receptor
      (EGFR) activation by suppressing the phosphatases PP2a and SHP-2. DMC also
      increased the interaction between EGFR and Cbl and induced the tyrosine
      phosphorylation of Cbl. The results suggest that DMC may have antitumor effects
      on prostate cancer cells via AMPK-induced down-regulation of HSP70 and EGFR. 

PMID- 22849867
TI  - A story about a word: does narrative presentation promote learning of a spatial
      preposition in German two-year-olds?
AB  - We trained forty German-speaking children aged 1;8-2;0 in their comprehension of
      UNTER [UNDER]. The target word was presented within semantically organized input
      in the form of a 'narrative' to the experimental group and within 'unconnected
      speech' to the control group. We tested children's learning by asking them to
      perform an UNDER-relation before, immediately after, and again one day after the
      training using familiarized and unfamiliarized materials. Compared to controls,
      the experimental group learned better and retained more. Children with advanced
      expressive lexicons in particular were aided in generalizing to unfamiliarized
      materials by the narrative presentation. This study extends our understanding of
      how narrations scaffold young children's enrichment of nascent word knowledge.

PMID- 22849868
TI  - Integrated QSAR study for inhibitors of Hedgehog Signal Pathway against multiple
      cell lines:a collaborative filtering method.
AB  - BACKGROUND: The Hedgehog Signaling Pathway is one of signaling pathways that are
      very important to embryonic development. The participation of inhibitors in the
      Hedgehog Signal Pathway can control cell growth and death, and searching novel
      inhibitors to the functioning of the pathway are in a great demand. As the matter
      of fact, effective inhibitors could provide efficient therapies for a wide range
      of malignancies, and targeting such pathway in cells represents a promising new
      paradigm for cell growth and death control. Current research mainly focuses on
      the syntheses of the inhibitors of cyclopamine derivatives, which bind
      specifically to the Smo protein, and can be used for cancer therapy. While
      quantitatively structure-activity relationship (QSAR) studies have been performed
      for these compounds among different cell lines, none of them have achieved
      acceptable results in the prediction of activity values of new compounds. In this
      study, we proposed a novel collaborative QSAR model for inhibitors of the
      Hedgehog Signaling Pathway by integration the information from multiple cell
      lines. Such a model is expected to substantially improve the QSAR ability from
      single cell lines, and provide useful clues in developing clinically effective
      inhibitors and modifications of parent lead compounds for target on the Hedgehog
      Signaling Pathway. RESULTS: In this study, we have presented: (1) a collaborative
      QSAR model, which is used to integrate information among multiple cell lines to
      boost the QSAR results, rather than only a single cell line QSAR modeling. Our
      experiments have shown that the performance of our model is significantly better
      than single cell line QSAR methods; and (2) an efficient feature selection
      strategy under such collaborative environment, which can derive the commonly
      important features related to the entire given cell lines, while simultaneously
      showing their specific contributions to a specific cell-line. Based on feature
      selection results, we have proposed several possible chemical modifications to
      improve the inhibitor affinity towards multiple targets in the Hedgehog Signaling
      Pathway. CONCLUSIONS: Our model with the feature selection strategy presented
      here is efficient, robust, and flexible, and can be easily extended to model
      large-scale multiple cell line/QSAR data. The data and scripts for collaborative
      QSAR modeling are available in the Additional file 1.

PMID- 22849869
TI  - Two-stage model of nanocone formation on a surface of elementary semiconductors
      by laser radiation.
AB  - In this work, we study the mechanism of nanocone formation on a surface of
      elementary semiconductors by Nd:YAG laser radiation. Our previous investigations
      of SiGe and CdZnTe solid solutions have shown that nanocone formation mechanism
      is characterized by two stages. The first stage is characterized by formation of
      heterostructure, for example, Ge/Si heterostructure from SiGe solid solutions,
      and the second stage is characterized by formation of nanocones by mechanical
      plastic deformation of the compressed Ge layer on Si due to mismatch of Si and Ge
      crystalline lattices. The mechanism of nanocone formation for elementary
      semiconductors is not clear until now. Therefore, the main goal of our
      investigations is to study the stages of nanocone formation in elementary
      semiconductors. A new mechanism of p-n junction formation by laser radiation in
      the elementary semiconductor as a first stage of nanocone formation is proposed.
      We explain this effect by the following way: p-n junction is formed by generation
      and redistribution of intrinsic point defects in temperature gradient field - the
      thermogradient effect, which is caused by strongly absorbed laser radiation.
      According to the thermogradient effect, interstitial atoms drift towards the
      irradiated surface, but vacancies drift to the opposite direction - in the bulk
      of semiconductor. Since interstitials in Ge crystal are of n-type and vacancies
      are known to be of p-type, a n-p junction is formed. The mechanism is confirmed
      by the appearance of diode-like current-voltage characteristics after i-Ge
      irradiation crystal by laser radiation. The mechanism in Si is confirmed by
      conductivity type inversion and increased microhardness of Si crystal. The second
      stage of nanocone formation is laser heating up of top layer enriched by
      interstitial atoms with its further plastic deformation due to compressive stress
      caused by interstitials in the top layer and vacancies in the buried layer.

PMID- 22849870
TI  - Clinical signs, therapy and zoonotic risk of pet guinea pigs with
      dermatophytosis.
AB  - Systematic studies about pet guinea pigs with dermatophytosis are rare. The aim
      of this study was to evaluate clinical signs, therapy and zoonotic risk of pet
      guinea pigs with dermatophytosis. Questionnaires from both owners (n = 74) of pet
      guinea pigs with dermatophytosis and their veterinarians (n = 101) were analysed
      regarding clinical signs, therapy and data pertinent to zoonotic potential.
      Trichophyton (T.) mentagrophytes was found in 97% of cases. In the weeks
      preceding the onset of the clinical signs, a new guinea pig joined the household
      in 43% of cases. One third of the affected guinea pigs had lived in the household
      for less than 3 months. Predominant clinical signs were alopecia (83%), scaling
      (73%) and crusting (70%). The most commonly affected body site was the head
      (75%). In approximately one quarter of the cases humans showed clinical signs of
      dermatophytosis, in half the households, only children were affected. Skin
      lesions were seen most often on the face, the neck and the arms. Pet guinea pigs
      carrying dermatophytes must be considered a serious zoonotic risk for their
      owners, especially for children. A major risk factor for dermatophytosis seems to
      be a recent acquisition of a new guinea pig.

PMID- 22849872
TI  - Endocrine-metabolic pathophysiologic conditions and treatment approaches after
      kidney transplantation.
AB  - OBJECTIVE: To review pathophysiologic conditions and diagnostic and therapeutic
      approaches in the management of endocrine-metabolic disorders after kidney
      transplantation (KT). METHODS: We discuss the assessment of diabetes mellitus
      (DM), hyperlipidemia, hypertension, and disturbances of bone and mineral
      metabolism after KT. RESULTS: KT offers patients with end-stage kidney disease
      substantial improvement in life expectancy and quality of life. Despite
      amelioration of renal dysfunction, however, these patients are at risk for the
      deterioration of existing and the development of new endocrine pathologic
      conditions. Pretransplant DM and new-onset diabetes after transplantation are
      associated with worse patient and graft survival. Little is known about
      preventing new-onset diabetes after transplantation and managing DM shortly after
      KT. In addition to glycemic control in patients with diabetes, management of
      cardiovascular risk factors includes appropriate recognition and treatment of
      hypertension and dyslipidemia. After KT, patients are at considerable risk for
      derangements in calcium and vitamin D metabolism. Immunosuppressive medications
      may cause compromised glucose and lipid metabolism, which may, in turn,
      contribute to the progression of preexisting and the development of new
      posttransplant endocrinopathies. CONCLUSION: Clinical care of kidney transplant
      patients should include a comprehensive endocrine assessment before and after KT
      in close collaboration with transplant nephrology providers. A referral to an
      endocrinologist should be initiated early during the pretransplant stage, and
      collaborative management should be maintained in kidney transplant patients to
      improve clinical outcomes.

PMID- 22849873
TI  - Thyroid cancer diagnosis and therapy: introduction.

PMID- 22849874
TI  - Current guidelines for the management of thyroid nodules.

PMID- 22849875
TI  - Recurrent differentiated thyroid cancer.
AB  - OBJECTIVE: To discuss the risk of recurrence in patients with differentiated
      thyroid cancer and emphasize the importance of risk-group stratification.
      METHODS: Common risk factors associated with recurrent thyroid cancer are
      outlined, and appropriate management strategies are reviewed. RESULTS: The
      overall prognosis in patients with differentiated thyroid cancer is excellent.
      Factors associated with recurrent thyroid cancer include extrathyroidal extension
      of the primary tumor, bulky nodal metastatic lesions, macroscopic local invasion,
      and aggressive histologic subtypes. The locoregional recurrence and mortality are
      higher in patients with high-risk thyroid cancers. Patients initially presenting
      with locally aggressive and advanced thyroid cancer have a higher incidence of
      recurrent disease in the thyroid bed or nodal metastasis. These patients also
      have a high incidence of distant metastatic lesions. Locally recurrent thyroid
      cancer may be seen in more than 25% of patients with aggressive differentiated
      thyroid cancer. Recurrent disease in the thyroid bed can be a difficult problem
      to manage because of the proximity of the tumor to the recurrent laryngeal nerve,
      visceral structures in the central compartment, and occasional involvement of the
      trachea or larynx. External beam radiation therapy after surgical treatment may
      be important for better local control in the thyroid bed region, especially in
      patients with poorly differentiated histologic features. The role of additional
      radioiodine therapy remains undefined at this stage. CONCLUSION: Management of
      patients with recurrent thyroid cancer necessitates a true multidisciplinary
      approach. These patients require close follow-up, with cross-sectional imaging
      and positron emission tomographic scanning in selected individuals.

PMID- 22849876
TI  - Radioiodine remnant ablation: current indications and dosing regimens.
AB  - OBJECTIVE: To review and comment on current indications for radioiodine remnant
      ablation (RRA) in patients with differentiated thyroid cancer. METHODS: The
      stratification of patients as potential candidates for RRA, the benefits and
      risks of RRA, and the optimal preparation and administered doses of iodine 131
      for RRA are discussed. RESULTS: When RRA for patients with low- and intermediate
      risk differentiated thyroid cancer is being considered, the benefits-including
      survival, influence on morbidity and recurrence, and ease of monitoring-should be
      weighed against the potential risks. RRA should have limited use in many low-risk
      patients, particularly those with stage I disease who are young and have small
      primary tumors, no lymph node involvement, and no extranodal invasion.
      Measurement of serum thyroglobulin 6 to 8 weeks after thyroidectomy during
      levothyroxine suppression can be used for further stratification of risk in these
      patients. RRA should be used only selectively in low- to intermediate-risk
      patients and reserved primarily for older patients with large tumors, extensive
      lymph node involvement, and high-risk (tall cell, insular) subtypes of
      differentiated thyroid cancer. Most low-risk to intermediate-risk patients who do
      warrant RRA can be prepared with recombinant human thyroid-stimulating hormone
      and given the smallest dose possible (30 to 50 mCi of iodine 131) for successful
      remnant ablation. Single-photon emission computed tomography-computed tomographic
      imaging and dosimetry are new tools that can help in the management of many
      patients with thyroid cancer. CONCLUSION: Although a large database study has
      shown a trend of increased use of RRA after thyroidectomy between 1990 and 2008
      in the United States, recent studies and guidelines suggest a more limited use in
      patients with low-risk disease, which may change this trend.

PMID- 22849877
TI  - Overview of molecular biomarkers for enhancing the management of cytologically
      indeterminate thyroid nodules and thyroid cancer.
AB  - OBJECTIVE: To provide information on molecular biomarkers that can help assess
      cytologically indeterminate thyroid nodules. METHODS: Published studies on
      immunohistologic, somatic mutation, gene expression classifier, microRNA, and
      thyrotropin receptor messenger RNA biomarkers are reviewed, and commercially
      available molecular test panels are described. RESULTS: Thyroid nodules are
      common, and clinical guidelines delineate an algorithmic approach including serum
      thyroid-stimulating hormone measurement, diagnostic ultrasound examination, and,
      when appropriate, fine-needle aspiration (FNA) biopsy for determination of a
      benign versus malignant status. In clinical practice, approximately 20% of FNA
      derived cytology reports are classified as "indeterminate" or follicular nodules
      that do not fulfill either benign or malignant criteria. In this setting, the
      actual risk for malignancy of a cytologically indeterminate nodule ranges from
      approximately 15% to 34%. Research describing molecular biomarkers from thyroid
      cancer tissue has been applied to FNA-derived thyroid nodule material. There is
      also a serum molecular marker that has been reported with goals similar to those
      for the FNA-derived molecular markers: to enhance the preoperative diagnosis of
      thyroid cancer and reduce the large number of patients who have a diagnostic
      surgical procedure for benign thyroid nodules. CONCLUSION: Progress toward the
      foregoing goals has been made and continues to evolve with the recent appearance
      of molecular biomarker tests that can be selectively applied for further
      assessment of cytologically indeterminate thyroid nodules.

PMID- 22849878
TI  - Accuracy of self-mixed small quantities of insulin.

PMID- 22849880
TI  - Palladium-catalyzed direct arylation of 5-chloropyrazoles: a selective access to
      4-aryl pyrazoles.
AB  - The use of a temporary protection by a chloro group at C5 of pyrazoles allows the
      synthesis of the 4-arylated pyrazoles, which were previously inaccessible by
      palladium-catalyzed direct arylation, with complete regioselectivity and in high
      yields using in most cases as little as 0.5-0.1 mol % Pd(OAc)(2) as the catalyst
      with electron-deficient aryl bromides. Moreover, from 5-chloro-1,3
      dimethylpyrazole, sequential catalytic C4 arylation, dechlorination, catalytic C5
      arylation reactions allowed the synthesis of a 4,5-diarylated pyrazole
      derivative.

PMID- 22849881
TI  - Impact of hospital-acquired Clostridium difficile.
AB  - BACKGROUND AND AIM: To investigate the impact of hospital-acquired Clostridium
      difficile infection (CDI) on hospital costs and patient length of stay. METHODS:
      Data from the 2007-2008 New York State Department of Health's Statewide Planning
      and Research Cooperative System (SPARCS) database was analyzed using regression
      analysis and descriptive statistics. RESULTS: After analysis of 4 853 800 patient
      discharges, the incidence rate of hospital-acquired CDI was 0.8 cases per 1000
      discharges. The estimated marginal cost associated with each hospital infection
      was approximately $29 000. The estimated annual cost of CDI in New York State was
      approximately $55 million with nearly 23 000 additional hospital days.
      CONCLUSIONS: The development of hospital-acquired CDI is associated with a
      significant increase in hospital costs and patient length of stay. Extrapolation
      of these estimates to all US hospitals suggests this condition represents a major
      burden to the US healthcare system. Our findings may help hospitals understand
      the impact of these infections, as well as potential implications if deemed
      preventable by Centers for Medicare & Medicaid Services and/or private payers.
      Additionally, this information may benefit hospitals or health care systems
      transitioning to alternative payment models, such as episode-based payments or
      accountable care. Healthcare providers and hospitals would benefit from better
      understanding the impact and frequency of these infections in order to best
      target preventive strategies.

PMID- 22849883
TI  - Immobilization of magnetic nanoparticles onto conductive surfaces modified by
      diazonium chemistry.
AB  - Core-shell gamma-Fe(2)O(3)@SiO(2) nanoparticles (NPs) substituted by PEG and
      NH(2) groups may be immobilized on metal surfaces (glassy carbon or gold)
      substituted by 4-carboxyphenyl groups through electrostatic interactions. Such
      immobilization is evidenced by (i) IRRAS owing to the Si-O band, (ii) SEM images,
      which show that the surface coverage by the NPs is nearly 100%, and (iii) the NPs
      film thickness measured by ellipsometry or AFM, which corresponds to about one
      NPs monolayer. Such NPs film is permeable to redox probes, which allows us to
      propose electrochemical methods based on direct or local measurements as a way to
      inspect the NPs assembly steps through their ability to alter mass and charge
      transfer. This process also applies to patterned polystyrene surfaces, and
      selective immobilization of NPs substituted by amino groups was carried out onto
      submillimeter patterns obtained by local oxidation. Biological applications are
      then expected for hyperthermia activation of the NPs to trigger cellular death.
      Finally, some tests were performed to further derivatize the immobilized NPs onto
      surfaces through either a covalent bond or electrostatic interactions. Future
      work will be dedicated to the recovery of such Janus NPs from the substrate
      surface.

PMID- 22849882
TI  - Susceptibility of the individual caseins in reconstituted skim milk to cross
      linking by transglutaminase: influence of temperature, pH and mineral equilibria.
AB  - The susceptibility of total casein and the individual caseins in reconstituted
      skim milk to transglutaminase (TGase)-induced cross-linking was studied as a
      function of incubation temperature (5-40  degrees C), pH (5.0-7.0) and mineral
      addition. Within the ranges studied, the level of total casein cross-linked
      increased with increasing temperature, pH and concentration of added trisodium
      citrate, whereas adding calcium chloride had the opposite effect. These effects
      can be largely related to the effects of these parameters on TGase activity. In
      addition, the parameters were also found to influence the susceptibility of kappa
      casein, and to a lesser extent beta-casein, to cross-linking, whereas the
      susceptibility of alphas1-casein was not affected. The susceptibility of kappa
      casein to cross-linking increased with increasing temperature and calcium
      chloride addition, but decreased with increasing pH and citrate content, whereas
      the susceptibility of beta-casein to TGase-induced cross-linking decreased with
      increasing temperature, but was not affected by other parameters. These findings
      highlight the fact that selection of environmental conditions during cross
      linking can be applied to tailor the surface, and hence possibly colloidal
      stability, of casein micelles in TGase-treated milk.

PMID- 22849884
TI  - Psychiatric disorders in children attending a Nigerian primary care unit:
      functional impairment and risk factors.
AB  - BACKGROUND: There is dearth of data on the level of functional impairment and
      risk factors for psychiatric morbidity in children attending primary care
      services in developing countries like Nigeria. The risk factors for psychiatric
      morbidity and functional impairment in children attending the primary care unit
      of a teaching hospital in Ilorin, Nigeria was therefore investigated to obtain
      data that could be used in improving service provision by primary care
      physicians. METHODS: A cross-sectional two-stage design was employed for the
      study. The first stage involved administration of the Child Behavior
      Questionnaire (CBQ) to 350 children while the children's version of the schedule
      for affective disorders and schizophrenia was used for the second stage involving
      157 children, all high scorers on CBQ (score of >= 7) and 30% of low scorers
      (score < 7). Diagnosis of psychiatric disorders was based on DSM-IV criteria.In
      addition, the Children Global Assessment Scale was used to assess the functional
      status of the children (score of <= 70 indicates functional impairment) while the
      mothers' mental health status was assessed with the 12-item version of the
      General Health Questionnaire, a score of 3 or more on this instrument indicate
      presence of mental morbidity. RESULTS: It was observed that 11.4% of the children
      had diagnosable psychiatric disorders and 7.1% were functionally impaired; and
      those with psychiatric disorders were more functionally impaired than those
      without. Thus, significant negative correlation was noted between CBQ scores and
      CGAS (r = 0.53; p < 0.001). Following logistic regression, younger age of
      children, frequent hospital attendance and maternal parenting distress
      independently predicted psychiatric morbidity while child psychopathology and
      maternal parenting distress predicted functional impairment. CONCLUSIONS: Child
      psychiatric disorders are prevalent in the primary care unit studied. Many of the
      risk factors identified in the study population are modifiable. Collaborative
      efforts between psychiatrists and primary care physicians could therefore help to
      reduce level of risk and functional impairment and psychiatric morbidity among
      children attending the primary care unit studied. It could also help improve
      referral rates of difficult cases to the child and adolescent psychiatric unit of
      the hospital.

PMID- 22849885
TI  - [Subocclusive transvenous approach of dural arteriovenous fistula].
AB  - INTRODUCTION: Dural arteriovenous fistulae (DAVF) are usually acquired and when
      presented with cortical venous drainage are associated with high risk of
      hemorrhage. They can be treated by arterial or venous embolization, by surgery or
      by the combination of both techniques. Transvenous approach induces venous sinus
      thrombosis increasing the risk of venous stroke and/or hemorrhage. OBJECTIVE:
      Review of all the cases of transvenous embolization of lateral sinus
      arteriovenous fistulas treated in our department. Our main objective is to
      evaluate the clinical/imaging results of this treatment and the second goal is to
      discuss possible advantages of the subocclusive approach in the first session of
      transvenous treatment. RESULTS: The authors present six clinical cases of DAVF
      with the following clinical symptoms: visual disturbances (3); ear pulsatile
      bruit (3); headaches (2); subarachnoid hemorrhage (1); subjective hearing loss
      (1); optic disc edema (1); hemiparesis (1). Angiographic classification was:
      Cognard IIa, (3), IIab (2) e IV (1), all of the lateral sinus. The main afferent
      branches arised from: ipsilateral ECA (6); ipsilateral ICA (6); ipsilateral VA
      (6); contralateral ECA (5); contralateral VA (5); contralateral ICA (3);
      ipsilateral PCA (1). Transarterial approach was the first approach in all
      patients with satisfactory but transient results. It was always followed by
      transvenous embolization of the lateral sinus with GDC coils. Subocclusive
      approach was achieved in five patients with the persistence of some afferent
      arteries. Follow-up angiography in four of them showed "spontaneous" thrombosis
      of the lateral sinus with clinical and angiographic cure. Thrombosis occurred
      once during the initial transvenous procedure. There were no complications or new
      neurological signs or symptoms in any patient. CONCLUSIONS: Transvenous treatment
      of DAVF has led to technical and clinical success without procedure
      complications. We think that subocclusive approach of the venous sinus with coils
      can cause less hemodynamic changes with a slower thrombosis rate and less
      complications, unchanging the angiographic and clinical resolution.

PMID- 22849886
TI  - [Surgical treatment of vesicourethral reflux in paediatric population].
AB  - BACKGROUND: Early diagnosis and adequate follow-up are fundamental principals for
      the treatment of vesicourethral reflux in children. The treatment options in
      these cases remain an individual choice based on multiple factors. OBJECTIVE: To
      determine and compare the effectiveness of two different surgical techniques
      (endoscopic and conventional) used on vesicourethral reflux treatment.
      METHODOLOGY: Cohort study, based on the clinical files of children and
      adolescents submitted to surgical treatment of vesicourethral reflux, between the
      1st January of 2000 and 30th April 2006. The study included one year period of
      follow-up. Multiple variables with a presumable influence on the therapeutic
      option were analysed. In cases of surgical treatment, effectiveness and safety of
      the surgical technique where determined. RESULTS: Included 46 children and
      adolescents, in a total of 68 refluxive units. Thirty seven of all renal units,
      where submitted to endoscopic treatment: the success rate with one injection of
      Deflux(r) was 62% (IC 95% [0.46; 0.78]), increasing for 78% (IC 95% [0.65; 0.91])
      when the second injection was performed. Thirty seven renal units were submitted
      to open surgery: Cohen procedure in 21 patients and nefrourethrectomy in two
      cases. Excluding the nefrourethrectomy, the classical surgery had a success rate
      of 97% (IC 95% [0.91; 1]). The reason between probabilities of success,
      considering endoscopic surgery vs. conventional surgery was 0,8 (IC 95% [0.68;
      0.97]). Registered thirteen complications, most of them (85%) after conventional
      surgery. DISCUSSION: The high complication rates determined for conventional
      surgery could justify the frequent option for endoscopic surgery in small
      centres, despite its lower success rates. CONCLUSION: This study confirms that
      this therapeutic option establishes a good commitment between prophylaxis safety
      and classical surgery effectiveness.

PMID- 22849887
TI  - [Comparative study of transvaginal sonography and outpatient hysteroscopy for the
      detection of intrauterine diseases].
AB  - INTRODUCTION: Intrauterine diseases are common morbid disorders. Endometrial and
      endocervical polyps, myomas, synechiae, uterine malformations, endometrial
      hyperplasia and endometrial cancer are cited among intrauterine pathology. The
      investigations using transvaginal sonography and outpatient hysteroscopy had been
      a gold standard. Transvaginal sonography shows endometrial thickness and
      heterogeneous variations within the echogenecity of the endometrium uterine
      pathology. Transvaginal sonography is easy to apply for evaluation of
      intrauterine pathology and it has high sensitivity to diagnostic for intrauterine
      disorders. Hysteroscopy was used the gold standard control. It permitted the
      better identification of intrauterine pathology but the histologic examination
      has been used for definitive diagnostic. Difficulty apprenticeship this technique
      had very decrease your access. OBJECTIVES: To evaluate the efficiency of
      transvaginal ultrasonography and outpatient hysteroscopy in the diagnosis of
      intrauterine pathology. SUBJECTS AND METHODS: The study conducted was a
      retrospective diagnostic-type test. They involved a total of 469 women underwent
      diagnostic hysteroscopy in 2006 in Campinas University. Seventy-nine women were
      excluded due to lack of ultrasound results in their medical charts. One-hundred
      and forty-seven premenopausal women and two-hundred and forty-three
      postmenopausal women. For statistical analysis, the sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy. The gold
      standard of the ultrasonography was the hysteroscopy and the gold standard of the
      hysteroscopy was the endometrium biopsy. RESULTS: The mean age of postmenopausal
      women was 61 +/- 9.4 years. We observed 6.6% of endometrial hyperplasia and
      cancer and 54% of endometrial polyps. Ultrasonography had a sensitivity of 95.6%,
      a specificity of 7.4% and an accuracy of 53.7%, while hysteroscopy had a
      sensitivity of 95.7%, a specificity of 83% and an accuracy of 88.7%. The mean age
      of premenopausal women was 40 +/- 8.2 years. Endometrial cancer was not observed
      and two cases of endometrial hyperplasia were found. We observed 34% of
      endometrial polyps. Sensibility was 52.9%, specificity was 68.4% and the accuracy
      was 61.2% for polyps on ultrasonography while in hysteroscopy was 78.8%, 67.6%
      and 73.1% respectively. For myoma, sensitivity was 70.6% and 64.3%, specificity
      was 44.3% and 98.1% and accuracy was 63.3% and 91.2% in ultrasonography and
      hysteroscopy respectively. CONCLUSION: Hysteroscopy had better diagnostic
      accuracy than ultrasonography for the detection of intrauterine pathology.

PMID- 22849888
TI  - [Diabetic retinopathy and associated conditions, what relationship? A study in
      Portuguese patients with type 2 diabetes].
AB  - BACKGROUND AND AIMS: Diabetic retinopathy is the leading cause of blindness in
      adults in Western countries. There are few studies about this microvascular
      complication in the Portuguese population. The aim of the present study is to
      establish the relationship between diabetic retinopathy, risk factors and
      associated conditions, in a group of patients with type 2 diabetes mellitus.
      MATERIAL AND METHODS: We performed a descriptive, transversal and case-control
      study that included 874 patients - 437 with and 437 without diabetic retinopathy,
      respectively. Data were collected from electronic medical records, in the
      Portuguese Diabetes Association with a first consult of Diabetology. RESULTS: The
      group with retinopathy had significantly higher values of HbA1c, systolic blood
      pressure and years of diagnosis, compared with the group without retinopathy
      (p<0.05). Regarding the levels of HbA1c, both groups showed more than 70% of
      patients outside the target value (HbA1c>6.5%) but in the subgroup with
      retinopathy, the percentage of patients in these conditions was higher (91.3%)
      compared to control group (73.2%) (p<0.05). The prevalence of hypertension in the
      sample was 73%. It was found that the group with retinopathy had a significantly
      higher prevalence of hypertensive patients (79.6% versus 66.4%) (p<0.05). The
      prevalence of nephropathy was higher in the group with retinopathy (35.6% versus
      0.8%) (p<0.05). CONCLUSION: There is a positive correlation between retinopathy
      and hypertension, glycaemic control and nephropathy. Thus, it is extremely
      important to control blood pressure and to educate patients about the benefits of
      a good glycaemic level.

PMID- 22849890
TI  - [Retroperitoneal laparoscopic nephrectomy in children younger than nine years
      old: state of the art].
AB  - INTRODUCTION AND AIM: In Portugal, there is very few experience in pediatric
      retroperitoneoscopy. The authors present the first Portuguese series of
      retroperitoneal laparoscopic nephrectomies (RLN) in children younger than nine
      years-old, as well as a literature review about the theme. MATERIAL AND METHODS:
      Retrospective analysis of clinical charts of all children submitted to RLN
      between January 2009 and December 2009 in a Pediatric Surgery Department. The
      literature review was made searching related articles in Medline. RESULTS: Eight
      RLN were preformed. The medium age of the patients was 4,5 years-old (minimum =
      11 months, maximum = 8,6 years). The indications for surgery were: four
      multicystic kidneys, three reflux nephropathy, and one obstructive nephropathy.
      Four RLN were preformed on the left side. The medium operative time was 99
      minutes (minimum = 50 minutes, maximum = 180 minutes). There was a shortening of
      operative time as the surgical team got more experienced. There were no
      conversions to open surgery. Medium hospital stay was 1,5 days (minimum = 1 day,
      maximum = 2 days). There were no intra-operative and no post-operative
      complications. CONCLUSIONS: RLN is feasible in children younger than nine years
      old and should be considered standard treatment in pediatric population.

PMID- 22849889
TI  - [Lifestyles and self-rated health, in Portuguese elderly from rural and urban
      areas].
AB  - The perception of health status is essential for better planning in health, not
      only due to its role as a determinant of health, but also because it is related
      with the adoption of health-promoting behaviours. The aim of the present study
      was to explore the relationship between lifestyles and self-rated health, in
      Portuguese elderly, according to their residence in rural or urban areas. We
      evaluated 80 individuals from Rebordelo, Tras-os-Montes (rural area) and 383 from
      Porto (urban area), with 60 or more years and with four or less years of
      education. Data were collected by trained interviewers, through a structured
      questionnaire, to evaluate social, demographic, health and behavioural
      characteristics. Anthropometric measures were also obtained. Leisure-time
      physical activity, tobacco, alcohol and fruit and vegetable consumption were the
      lifestyles evaluated. To evaluate self-rated health, each person rated their
      health status, according to five options (excellent, very good, good, reasonable
      or poor), later grouped into two: poor versus the others. Odds ratio (OR) and 95%
      confidence intervals (95%CI) were calculated by unconditional logistic
      regression, after adjustment for sex and education. About 41% of the elderly from
      the rural area and 32% from the urban area rated their health status as poor. In
      multivariate analysis, in the rural area, poor self-rated health was inversely
      associated with the practice of leisure-time physical activity (OR = 0.22, 95%CI
      0.06-0.80). In urban area, alcohol consumption was associated with a lower
      probability of self-rating health as poor (considering not drinking as reference,
      >0-15 g alcohol/day: OR = 0.42, 95%CI 0.24-0.72; >15 g alcohol/day: OR = 0.60,
      95%CI 0.32-1.11). In the rural area, a positive association between fruit and
      vegetable consumption and poor self-rated health was found (>= 5 vs. <5
      portions/day: OR = 5.21, 95%CI 1.14-23.83), while in the urban area there was an
      inverse association (OR = 0.75, 95%CI 0.45-1.25). Poor Self-rated health was
      inversely associated with leisure-time physical activity in the rural area, and
      with the consumption of alcoholic beverages in the urban area. The consumption of
      fruit and vegetables was associated with self-rated health in both populations,
      but while in the rural area the consumption of 5 or more servings per day was
      associated with a poor perception of health, in the urban area this association
      was in the inverse direction.

PMID- 22849891
TI  - [Spinal muscular atrophy: descriptive analysis of a case series].
AB  - INTRODUCTION: Spinal Muscular atrophy (SMA) is a genetically determined specific
      neuromuscular disease, characterized by the deterioration of spinal a motor
      neurons, causing progressive muscular atrophy and weakening. It is genetically
      determined, with the absence or mutation of the survival motor neuron 1 (SMN1) as
      a hallmark. A similar copy of the SMN1, named SMN2, modulates the severity of the
      disease. Several types of the disease have been described along with several
      classification systems based either on the age at onset of symptoms or on the
      maximum function achieved. SMA leads to a vast group of secondary manifestations
      in various organ systems, particularly the respiratory, muscle-skeletal and
      gastrointestinal. GOAL: To study the population with the diagnosis of SMA
      (clinical and/or genetic) followed in the Physical Medicine and Rehabilitation
      outpatient clinic (PMR) of the Hospital de Dona Estefania (HDE) in Lisbon, from
      January 2007 to October 2009. METHODS: The authors conducted a retrospective
      study focusing on socio-demographic, clinical parameters, evolution and
      complications of the disease. RESULTS AND DISCUSSION: Twelve children were
      enrolled in the study, with age ranging from 0 months to 21 years, four diagnosed
      with SMA type III, seven with SMA type I and one with SMA II. An inverse relation
      was found between the severity of the course of illness and the age at onset and
      maximum motor function achieved. All patients sustained recurrent lower
      respiratory infections during the course of the disease. Respiratory
      insufficiency complicated by cardio-respiratory arrest was the cause of death in
      the deceased patients. The main musculoskeletal complication was the development
      of contractures in the main joints of the lower limbs, as well as scoliosis.
      Dysphagia was the main gastroenterological complication. CONCLUSION: The authors
      conclude that the lack of acquisition of motor developmental milestones is
      correlated to worse vital and functional prognosis.

PMID- 22849892
TI  - [Parotidectomy through periauricular incision].
AB  - BACKGROUND: Blair or modified Blair approaches that combine periauricular and
      cervical incisions are used in almost all parotid surgeries. The aim of this
      study was to evaluate the results of treatment of parotid surgical diseases using
      only periauricular incision. METHODS: 36 consecutive patients with parotid tumors
      were reviewed. Pleomorphic adenoma (17 cases) was the most common pathologic type
      followed by other benign tumors (9 cases), carcinoma (5 cases), parotid cyst (3
      cases) and chronic parotiditis (2 cases). All parotidectomies were performed
      through a periauricular incision. In presence of carcinoma, upper cervical
      lymphadenectomy was conducted through a transverse cervical incision. The wounds
      were closed with subcutaneous synthesis without skin suture. RESULTS: The parotid
      tumors were removed in all cases without complementary skin approach. The
      incisions had good esthetic result and almost imperceptible scars were verified
      after six months. The patients were very satisfied with the appearance of the
      operative scar. All patients complained hypostesia of the operative area during a
      period not longer than six months. Temporary postoperative facial weakness
      occurred after 28 operations and was permanent in three of patients operated upon
      for carcinoma. Transitory ear discomfort occurred in 22 patients. Two cases of
      local infection were recorded. All of these complications have been described
      previously by other authors using other incisions and are mostly due to removal
      of the gland. CONCLUSION: The results of the present study indicate that
      periauricular incision is a good and highly esthetic option for surgical approach
      of the parotid.

PMID- 22849893
TI  - [Transhiatal esophagectomy with gastric transposition for esophageal replacement
      in post-corrosive stricture in children].
AB  - BACKGROUND & PURPOSE: Despite potential advantages of gastric transposition there
      are some concerns about this surgical technique of esophageal substitution in
      children. In the current study the morbidity and functional outcome are surveyed
      in a series of patients undergoing gastric transposition due to extensive post
      corrosive esophageal strictures. METHODS: Retrospective analysis of children
      proposed for esophageal replacement from September 2003 through April 2007 after
      endoscopic dilations failure. Demographic and pathological features, intra and
      postoperative complications and clinical outcome were assessed. Continuous
      variables are expressed as median [range]. RESULTS: There were six children (age:
      4.3 [2.5;14.4] years) with esophageal structures secondary to corrosive alkali
      ingestion; five had been submitted to dilation (n = 8 [7;27]) and one had
      undergone gastrostomy. Esophagectomy without thoracotomy plus gastric
      transposition were uneventfully performed in all cases. There was no mortality.
      On postoperative course there was one hypertensive pneumothorax and one
      pneumonia. With a follow-up of 50 [38;80] months, two children experienced mild
      dysphagia that was promptly solved by one or two sessions of dilations of
      esophagogastric anastomosis; both weight and height were between 5th and 75th
      centiles; none presented gastrointestinal or recurrent respiratory symptoms,
      anemia or substitute dilation. CONCLUSION. Transhiatal esophagectomy with gastric
      transposition in posterior mediastinum presented low morbidity and excellent
      functional outcome with no impairment of growth or respiratory function, at least
      on short/medium term.

PMID- 22849895
TI  - [Motor coordination in premature and/or low birth weight children].
AB  - OBJECTIVE: Our evaluation pretends to evaluate the influence of prematurity /
      very low birthweight in motor coordination, in a group of premature children
      without clinical evidence of neurological injury. METHODS: We assessed 58 ex
      premature children born between 1997 and 2000 in Central's Portugal Region, of
      which 31 participated in the study. The whole-body coordination test was
      performed to assess motor performance. RESULTS: Our sample was composed of 31
      children, 14 males and 17 females, divided into two age groups: from 7 to 8 years
      and 9 to 10 years. The mean gestational age was 30 and 30.1 weeks respectively
      for the age groups from 7 to 8 years and 9 to 10 years. The birthweight was, on
      average, 1059 and 1169 g respectively for the group of 7 to 8 years and 9 to 10
      years. Based on the results of motor quotient we found 71% (22) of children with
      reduced motor ability, 23% (7) with impaired motor skills, and only 6% (2), with
      normal motor coordination. CONCLUSIONS: From our study there was no evidence that
      premature and low birthweight children, have worse motor coordination, that
      female children have better coordination than the male, and there was not
      evidence also that children practicing physical activity have better
      coordination.

PMID- 22849894
TI  - [What is the nutrition and lifestyle profile in oncology patient? Cross-sectional
      study].
AB  - BACKGROUND: Cancer aetiology is multifactorial and risk factors include: obesity,
      central adiposity, sedentarism, excessive or deficient intake of foods and/or
      nutrients with pro-carcinogenic effects vs protective ones. OBJECTIVES: To
      evaluate the pattern of nutritional status, life styles, physical activity and
      diet in a cohort of cancer patients. METHODS: This pilot cross-sectional study
      was conducted in 64 patients referred for radiotherapy at the Radiotherapy
      Department of the University Hospital of Santa Maria (CHLN). Evaluations were:
      waist circumference associated with potential cardio-metabolic risk, body
      composition by Tetrapolar Bioimpedance Analysis (XITRON(r)), Body Mass Index,
      dietary intake pattern with a short food frequency questionnaire, physical
      activity with Jackson questionnaire. RESULTS: The most frequent diagnosis were
      breast and colorectal cancers; 53% of patients were overweight/obese, and there
      was a significant correlation between this nutritional pattern and weight gain in
      comparison with usual weight (p<0.005). There were 78% of patients with a waist
      circumference above the maximum cut-off limit, indicating moderate/ high cardio
      metabolic risk, and most were female patients (87%). The great majority of
      patients (61%) had excessive fat mass highly above the maximum recommended cut
      off value, especially male patients (74%). The dietary pattern was poor in
      vegetables (55%) and excessive in meat and simple carbohydrates (78%); physical
      activity was low with a high prevalence of sedentarism. CONCLUSIONS: This
      population presented excessive body weight, excessive fat mass, high cardio
      metabolic risk, sedentarism and an unbalanced diet poor in protective
      foods/nutrients. This population's life styles and nutritional pattern, may be
      considered of risk in oncology disease. The elevated and growing incidence of
      cancer in Portugal, reinforces the need for further research in order to identify
      nutritional factors involved in the etiology/evolution and probably prognosis of
      cancer.

PMID- 22849896
TI  - [Abdominal compartment syndrome: survey on the awareness of Portuguese general
      surgeons].
AB  - The Abdominal Compartment Syndrome (ACS) is a clinical entity recognized for over
      a century, but only recently its risk criteria, monitorization and treatment have
      been defined by the World Society of the Abdominal Compartment Syndrome (WSACS).
      The general surgeon's involvement is vital since this syndrome is common in
      surgical patients and because its treatment may culminate in a laparostomy. 250
      questionnaires of 17 questions were distributed among general surgeons attending
      the XXVIII Portuguese Congress of Surgery. The data were analyzed using SPSS(r)
      v16. We received 36,4% (91) of the delivered questionnaires, most of which from
      male surgeons (63,7%), from central hospitals (75,8%), working 42 h per week
      (70.3%), whose average of age was 38 years. About half of the respondents
      received training in Intensive Care Units. All surgeons had already heard about
      measuring the Intra- abdominal Pressure (IAP), which was being performed at 89%
      of their hospitals. About 40% of surgeons only admitted intra-abdominal
      hypertension above 20 mmHg (only 22% indicated the correct value of 12 mmHg).
      36,3% of surgeons suggested that a decompressive laparostomy must be carried out
      for primary ACS if IAP greater then 20 mmHg with new organ failure; 36.3%
      favoured the "Vacuum-pack"-like system, and 56% only re-operate the patients "as
      needed". 48,4% of surgeons had already performed decompressive laparostomy, 66%
      of which had residence training in a ICU (p = 0,005). Respondents also pointed an
      average mortality related to ACS of 81% without laparostomy, and a reduction to
      38,5% after performing that procedure. Only 26% of the surgeons were aware of the
      WSACS consensus definitions and recommendations, of those, 83% had already
      performed a laparostomy (P<0,001). It can be concluded that, in spite of
      recognizing the ACS as a clinical entity, portuguese general surgeons are quite
      unaware of the WSACS definitions and treatment guidelines, urging the need for
      its divulgation.

PMID- 22849897
TI  - [Motivation and support provided on training: a longitudinal study of a cohort of
      family medicine residents].
AB  - BACKGROUND: Having as main goal the development of a culture of professional
      excellence, the Family Medicine residency currently intends to correspond to the
      principles of adult learning approach, in which motivation for practicing is
      essential. OBJECTIVES: (1) To analyze the variability of Family Medicine
      residentes professional motivation, throughout the residency training; (2) To
      characterize Family Medicine residents perception about the support provided on
      training, during the residency; (3) To analyze the variability of Family Medicine
      residents perception about the support provided by the supervisor, throughout the
      residency. METHOD: Observational, quantitative and longitudinal study (2005-2008)
      of Family Medicine residents who participated in a survey on professional
      motivation. At the beginning of the residency in 2005 (N = 109) in Portugal, they
      were submitted to three assessment moments (n = 69) by a postal survey using a
      questionnaire with 57 Likert scale items, representing motivational variables-
      professional project, professional commitment, initial motivation, intrinsic
      motivation, self-efficacy expectations, self-control expectations, assertiveness
      and perception of the support provided on training program. Descriptive
      statistics and analytic tests (ANOVA--GLM repeated measures) were used to study
      the variability of the cognitive dimensions (a = 0,05). RESULTS: Although
      motivated to Family Medicine practice (response rate = 47.8%, at the study
      entry), the physicians professional motivation variability along the residency
      has presented slightly positive, at the end of the study, but not statistically
      significant. The physicians of our cohort responded by assigning a relatively
      high average levels in almost all items of the scale support provided on training
      during the residency, and its variation showed a positive trend, at the end of
      the study. CONCLUSIONS: This study produced results of an important phenomenon on
      which there is no published information in Portugal. It provides substantial
      evidence on the progression of professional motivation of this physicians' cohort
      and on their perception about strategies used by the supervisor. The structuring
      of residency program may include individual strategies aimed to increase the
      Family Medicine residents' motivation, with benefits for their performance.

PMID- 22849898
TI  - [Continuous subcutaneous insulin infusion].
AB  - BACKGROUND: Continuous subcutaneous insulin infusion (CSII) and multiple daily
      injections (MDI) represent two strategies of intensive insulin therapy, obtaining
      a strict metabolic control. The importance of such rigorous metabolic control in
      reducing the frequency and severity of diabetes long-term complications was
      highlighted by the Diabetes Control and Complication Trial (DCCT). AIM: To review
      the experience in the use of ISCI at Hospital Sao Joao, comparing it with the
      therapeutic modality of MID, regarding metabolic control, weight and body mass
      index (BMI), microalbuminuria, frequency of adverse events, lipid profile and
      quality of life. METHODS: This retrospective, observational study included 25
      type 1 diabetic patients followed-up on Endocrinology outpatient at Hospital Sao
      Joao, receiving CSII for more than 3 months after they were treated with MDI also
      for a period exceeding 3 months. For both periods of treatment, clinical data
      were obtained on the quality of glycaemic control (assessed by the levels of
      glycated hemoglobin--A1c), lipid profile, weight and body mass index (BMI) and
      microalbuminuria. To evaluate the impact on quality of life we used the ADDQoL
      questionnaire. A questionnaire was also used to determine the frequency of
      adverse events (severe hypoglycemia and ketoacidosis). RESULTS: The sample of 25
      subjects with mean age of 33.35 +/- 9.59 years, with a duration of disease, on
      average, of 17.1 +/- 8.15 years and receiving ISCI for an average of 2.48 +/- 1
      08 years, obtained a decrease of 1.1% (p = 0.001) on the median value of A1c
      between 3 and 6 months of treatment when compared to MDI, reduction sustained
      throughout the analyzed period. The variation of the daily insulin requirements
      after pump placement was 12.75 units of insulin (p = 0.015), equivalent to a
      decrease of 0.20 units/kg (p = 0.023). The median of the distribution of BMI
      decreased 0.48 kg/m2 (p = 0.507) during CSII. The parameters of lipid profile and
      microalbuminuria showed no trend upward or downward after institution of CSII.
      The score obtained in the ADDQoL questionnaire was greater with CSII, the
      difference between the medians of the score distribution, before and after pump
      placement, was 0.056 (p = 0.92). There was a subjective perception of reduced
      frequency of adverse events with ISCI. CONCLUSION: The introduction of CSII
      allowed optimization of metabolic control, reduction of the daily insulin
      requirements and achievement of a higher level of satisfaction with no change in
      lipid profile, no weight gain and without increasing the frequency of adverse
      events.

PMID- 22849899
TI  - [Stress and satisfaction of mothers in neonatal intensive care].
AB  - INTRODUCTION: The admission and stay in a Neonatal Intensive Care Unit represents
      an anxious experience to parents, because of their frustrated expectations and
      the confrontation with the possibility of newborn's death. The aims of this study
      were to assess how mothers cope with physical characteristics of the context,
      with treatments and with the loss of the idealized parental role; to assess how
      mothers evaluate the medical and nurse staff performance; and to assess the
      degree of satisfaction with the Service. MATERIAL AND METHODS: A sample of 100
      mothers, whose newborns were admitted at the Neonatal Intensive Care Unit,was
      asked to fulfil a specific survey. RESULTS: In a general way, according to the
      mean of all stress subscales, the total experienced stress was moderate.
      Significant associations or differences between scholarity and stress were not
      found, as well as with mother's age. The loss of parental role was the most
      anxious factor for mothers. The satisfaction with medical team was inversely
      related to stress. Mothers were satisfied with nurse team performance.
      CONCLUSION: The loss of the idealized parental role is the most anxious
      experience for the mothers. The observed results highlight the need for the
      continuous change of the neonatal unit in a more warming environment for the
      mothers and their newborns.

PMID- 22849900
TI  - [New vaccines].
AB  - INTRODUCTION: Vaccines prevent more cases of diseases than any other medical
      treatment. However, information on new vaccines introduced in the market and not
      included in the National Vaccination Program (NVP) is often sparse, and their
      knowledge limited. OBJECTIVES: Evaluate general and specific knowledge of healthy
      children's parents on three vaccines not included in the NVP: pneumococcal
      (PCV7), varicella (Var) and rotavirus (RV). METHODS AND MATERIAL: Transversal
      descriptive study, in the format of a questionnaire applied randomly to parents
      of children that attended three Primary Care Centers of Portugal (Lisbon, Porto
      and Queluz), between March and April 2007. We analyzed sociodemographic
      parameters, level of knowledge (the existence and type of preventable disease by
      the three vaccines), its realization or intention of realization, and the
      availability of acquiring them by parents. Statistic analysis used Qui-Squares
      and T-Student tests (CI>95%), with p<0,05 considered statistically significant.
      RESULTS: We interviewed 187 children's parents with a median age of 13 months.
      Most (82%) had incomplete schooling and a mean monthly income of 1256?. In 83% of
      the interviews, the parents knew at least one of the vaccines: pneumococcal
      (72%), varicella (42%) and rotavirus (1,3%), and applying the same order, the
      type of disease each vaccine prevented: 118/135 (87%), 83/84 (99%) and 21/24
      (87,5%). In 80% of cases, health care professionals provided the information to
      parents: pediatrician (67) and primary care doctor (49). Most (96%) parents
      considered the PCV7 the most important vaccine. Of the children evaluated, 93%
      had the NVS actualized, additionally, 39% had the pneumococcal vaccine, 0,5%
      varicella and 3% rotavirus vaccine. Knowledge about the varicella and rotavirus
      was associated with a higher academic level of the parents (40 vs 46,p = 0,018; 8
      vs 16,p = 0,026) and the acquisition of the pneumococcal and rotavirus vaccine
      with a higher income (1506? vs 1144?; p = 0,04) and (2283? vs 1162?; p = 0,04).
      CONCLUSION: With exception of the PCV7 the remaining vaccines are still
      insufficiently known. It is up to health care professionals to disclose
      information and encourage families for vaccination.

PMID- 22849901
TI  - [Predictors of poststroke depression: a retrospective study in a rehabilitation
      unit].
AB  - INTRODUCTION: Stroke can significantly limit functionality, a fact often not
      correlated with the neurological deficit itself. The psychiatric complications
      have been identified as key factors in post-stroke. Depression has shown to be
      the most common complication and the one associated with a worse prognosis. There
      is still uncertainty as to its etiology and risk factors. In the most recent
      systematic review, some factors are recognized: stroke severity, the degree of
      disability and cognitive impairment. Establishment of other factors wasn't
      possible due to methodological issues. Thus, it is urgent to define new factors
      that facilitate a timely diagnosis, which may lessen the negative effects on the
      rehabilitation process. OBJECTIVES: To determine the incidence of post-stroke
      depression (PSD) and to study variables described in the literature as possible
      predictors of PSD: sex, age, type of stroke, laterality, vascular territory and
      presence of aphasia. The study of the type of aphasia was defined as secondary
      endpoint. METHODS: Retrospective longitudinal study involving all patients
      admitted to a PMR ward, with the diagnosis of stroke de novo, between 1/1/2009
      and 31/12/2009. Demographic and clinical data was collected from 74 patients'
      files. EXCLUSION CRITERIA: 'previous stroke', 'prior psychiatric illness with
      mood disturbance' and 'antidepressant medication at the time of stroke'. SPSS
      11.5 was used for statistical analysis. RESULTS: The incidence of PSD was 44.6%.
      Amongst possible predictor factors tested, only the presence of aphasia showed a
      significant association with depression (p = 0.02). There was no relation with
      the type of aphasia. The other predictors tested showed no statistically
      significant correlation. There seems to be a relationship between male sex and
      the PSD (p = 0.07), which did not reach significance with this sample size (n).
      CONCLUSIONS: This study establishes aphasia as a predictive factor of PSD and
      excludes the remaining variables. The high incidence of PSD in this particular
      population agrees with the existing studies, but a different study is needed to
      justify the value found. Further studies are needed, not only to increase
      knowledge of risk factors for PSD, as to improve the outcomes of rehabilitation
      programs.

PMID- 22849902
TI  - On the limit of viability extremely low gestational age at birth.
AB  - BACKGROUND: Survival is not an adequate measure of success when managing preterm
      infants < 24 weeks gestational age (GA). OBJECTIVE: To evaluate neonatal
      morbidity, survival rate and outcome of preterm infants < 24 weeks GA at birth,
      in our Neonatal Intensive Care Unit. MATERIAL AND METHODS: Retrospective chart
      review, 1996-2009. Collected data included neonatal morbidity and mortality,
      follow-up at the outpatient department regarding to medical problems and
      neurodevelopmental and behavioural outcomes. RESULTS: 53 preterm neonates (27
      male/ 26 female) were included; weight at birth: 630 g (360-870); gestational
      age: 23.5 wks (22-24); outborn: 9 (17%); any antenatal steroid: 57%. Neonatal
      morbidity included: hypotension 68%; respiratory distress syndrome: 98%;
      pneumothorax: 11%; patent ductus arteriosus: 42%; noso sepsis: 72%; necrotizing
      enterocolitis (>2A): 54%; intraventricular hemorrhage (III+IV): 34%; retinopathy
      of prematurity (>2): 20%; bronchopulmonary dysplasia: 71%. Mortality rate was 87%
      (n = 46). Antenatal steroids rate was 71% and 54%, for survivors and deceased
      newborns, respectively. Out of the seven (13% of total) survivors aged between 7
      months and 14 years old (two under 24 months), five (71%) present major sequelae
      at the follow-up, while two (29%) exhibit normal "border line" development.
      CONCLUSIONS: Based on these findings it seems that other characteristics of the
      infants and pregnancies, and not gestational age alone, should be considered
      before a decision is taken.

PMID- 22849903
TI  - [Incapacity paradox of very-old people].
AB  - INTRODUCTION: People aged 80 years and over are the segment of the population
      that grows faster, and it is expected that by the year 2050 this group will
      represent 3.4% of the total population of the world (UN, 2002). With advancing
      age, despite disability and age-related losses, some people succeed in evaluating
      their health more positively, especially when comparing with others. This paradox
      is one of the biggest contradictions in the literature that focus the very-old
      and suggests the existence of moderating influences in the relation between
      objective and subjective health. OBJECTIVE: Analyze the dynamic of the
      relationship between objective health and physical health with advancing age.
      METHOD: It was used a sample of 991 community-dwelling participants, 698 women
      (70.4%), with ages between 65 and 101 years (mean age 74.1, SD 6.5). The General
      Health Questionnaire and the Questionnaire on Health and Lifestyles were used for
      collecting data. Socio-demographic information was also collected. RESULTS:
      Comparative analyses showed significant differences in subjective, objective and
      mental health among age groups. The older group (n = 207) was more likely to have
      worse objective health, with greater levels of disability (ADL and IADL), more
      vision difficulties, and a better subjective health. Differences between age
      groups were more significant in the question about how they evaluate their health
      comparing with other people. CONCLUSION: Despite the impaired functional capacity
      and increased psychological distress, people with 80 and more years old don't
      have a worse physical health or a more pessimistic self-rated health, especially
      when comparing with others. These results show that older people seem to have
      capabilities that can be channeled and directed to provide their own health.
      Knowing the characteristics of this group, considered the "biological elite" of
      this generation, will help to identify measures to promote successful aging.

PMID- 22849904
TI  - [Extended-spectrum beta-lactamase producing bacilli in a paediatric hospital].
AB  - BACKGROUND: Enterobacteriaceae are a common cause of invasive disease in
      children. The production of extended-spectrum beta-lactamase (ESBL) by these
      bacteria and consequent resistance to several antibiotics has increased. The
      paediatric data are scarce. AIMS: To identify children infected with ESBL
      producing bacilli, determining their prevalence in health care related infection
      and community-acquired disease. To analyse demographic, clinical, laboratory,
      therapeutic and follow-up data. To identify potential risk factors for infection
      by ESBL-producing organisms. METHODOLOGY: A case-control study, conducted in a
      level III paediatric hospital, from July 2007 to December 2009. All patients were
      identified from the microbiology database. Children infected by ESBL-producing
      bacilli were compared with a group with infection by non-ESBL producers, selected
      in a systematic way, given the bacteria, product and date of isolation.
      Statistical data analysis was performed using SPSS(r) 17.1. RESULTS: The ESBL
      producing phenotype was detected in 0.5% of Escherichia coli and 16.4% of
      Klebsiella spp identified. These bacteria were isolated in 23 children: 7
      Escherichia coli (30.4%), 15 Klebsiella pneumoniae (65.2%) and 1 Klebsiella
      oxytoca (4.3%). The most common diagnosis was urinary tract infection (39%).
      Hospital admission was required in 70% of the cases versus 50% controls
      (p=0.141), with mean duration stay of 69 days for cases and 36 days for controls
      (p=0.235). The mean time between admission and infection was 32 days in both
      (p=0.978). Health care related infections were identified in 70% of cases versus
      25% of controls (p=0.001). Infections due to ESBL producing organisms occurred in
      the community setting particularly in the last year of the study (n=4). The
      presence of chronic disease (p=0.022) and previous hospitalization (p=0.025),
      antibiotic use (p=0.008) and invasive ventilation (p=0.002) were more common in
      infection caused by ESBL-producing bacteria. Surgery (p=0.175) and the presence
      of a central venous catheter (p=0.189) were not risk factors. In a multivariate
      analysis, only prior invasive ventilation was an independent risk factor for
      infection by ESBL-producing bacteria (p=0.002, OR=7). CONCLUSIONS: The ESBL
      producing phenotype was detected in 0.5% Escherichia coli and 16.4% Klebsiella
      spp identified; mainly in health care related infections. The presence of chronic
      disease and previous hospitalization, invasive ventilation and antibiotic intake
      were more common in infections caused by these bacteria. Prior invasive
      ventilation was an independent risk factor.

PMID- 22849905
TI  - [Escherichia coli bacteraemia in a pediatric emergency service (1995-2010)].
AB  - BACKGROUND: Some authors reported an increase in relative incidence of E. coli
      bacteraemia in recent years. E. coli has been the third most frequently isolated
      bacteria in blood cultures at our emergency service between 1995 and 2009. AIM:
      To analyse trends, clinical, laboratory and microbiological data of E. coli
      bacteraemia in a level 3 pediatric hospital, in the last 16 years. METHODS:
      Retrospective analysis of cases with positive blood cultures for E. coli between
      1995-2010. Nosocomial infections were excluded. RESULTS: E. coli was identified
      in 32 children (19 boys); 15 cases (47%) were diagnosed in the second half of the
      study. The median age was 1,5 months: 13 (41%) were neonates, 23 (72%) were less
      than three months of age and 29 (91%) were less than 12 months. Fever was the
      most common symptom, present in 29 children (91%). In the neonatal period the
      median leukocyte count was 12,2 x 103/mL and median C reactive protein was 13
      mg/dL. Beyond the first month of age, the median leukocyte count was 16,7 x
      103/mL and median C reactive protein was 10 mg/dL. The diagnosis were: acute
      pyelonephritis (57%), sepsis (13%), urosepsis and meningitis (9% each), occult
      bacteremia (6%), cholangitis and appendicitis (3% each). Eight of 21 acute
      pyelonephritis were diagnosed in the neonatal period. One child died (sepsis) and
      two had brain abscesses after meningitis. Resistances were: 24% to ampicillin,
      12% to amoxicillin+clavulanate, 18% to cefalotin, 0% to cefotaxime and
      aminoglycosides. Resistances were higher in the neonatal period. CONCLUSIONS: We
      did not see an increase of community-acquired E. coli bacteraemia over the last
      16 years in our hospital. Infections occurred mainly in the neonatal period and
      first three months of life and the most frequent diagnosis was acute
      pyelonephritis. Leukocytosis is not always present, particularly in the neonatal
      period. A quarter of the E. coli was resistant to ampicillin. The outcome was
      favorable in most children and one died of sepsis.

PMID- 22849906
TI  - [Conditions for neonatal resuscitation in Portuguese delivery rooms: a national
      survey (2009)].
AB  - INTRODUCTION: In Portugal, since 1989, the rates of maternal, perinatal and
      neonatal mortality present a significant decrease, after the implemented
      perinatal network. The continuous assessment of the existing conditions at the
      different levels of perinatal care is essential to identify deviations from
      normality and may allow the optimization of quality of care. OBJECTIVES: To
      obtain information on and to evaluate the conditions and practices of neonatal
      resuscitation at the Portuguese delivery rooms, in order to propose measures for
      improvement of neonatal care. MATERIAL AND METHODS: An electronic questionnaire
      was sent to 35 hospitals with maternity. The survey included questions regarding
      to human and material resources, characteristics of delivery room practices used
      in stabilization / resuscitation of the newborn, number of deliveries and number
      of newborns transferred after birth per year, as well as issues related with the
      collaboration of obstetric teams. RESULTS: Thirty centres (86%) answered the
      questionnaire, 16 of the respondents were level III maternities/hospitals. In
      eight (27%) centres a paediatrician is present at all deliveries, whereas in the
      remaining centres a paediatrician is available only for risk situations. The
      material unavailable in some centres include cardio-respiratory monitoring
      equipment, support device with pressure controlled ventilation, oxygen blender,
      ventilator, CPAP (continuous positive airway pressure), neonatal transport
      incubators and equipments for thoracocentesis and paracentesis. The criteria used
      for prophylactic surfactant and oxygen use are very different among the various
      centres. All centres reported transferring newborns after birth, either because
      of lack of differentiation of care or vacant beds. The centres with perinatal
      support reported less cooperation of the obstetric teams. CONCLUSIONS: The care
      of the newborn in the national delivery rooms can and should be improved. It is
      necessary to adapt the equipment and human resources to the needs of each centre.
      Protocols and practices such as oxygen and "prophylactic" surfactant must be
      updated, transport after birth must be reduced and the communication with the
      obstetric teams should be improved.

PMID- 22849907
TI  - [Lung abscess and thoracic empyema: retrospective analysis in an internal
      medicine department].
AB  - INTRODUCTION: Lung abscess is a collection of necrotic and suppurated tissue
      located at the pulmonary parenchyma. Empyema is defined as the presence of pus in
      the pleural space. OBJECTIVES: To study the clinical and microbiological
      characteristics, treatment and prognosis of patients with lung abscess and/or
      empyema admitted to an Internal Medicine ward. METHODS: A retrospective analysis
      of medical records was performed, including all patients admitted to an Internal
      Medicine ward for lung abscess or empyema, between 2000 and 2008. RESULTS: Thirty
      patients were included (22 males/ eight females), accounting for 0.18% of all
      patients admitted in this ward in the same period. Three patients had pulmonary
      abscess, 18 empyema, and nine both diseases. The average age was 68.5 years (31
      to 90). The most frequent complaints were dyspnoea (90%), fever (73.3%), cough
      (66.7%), weight loss (60%) and chest pain (53.3%). The most frequent associated
      disorders were stroke associated disability (46.7%), heart failure (43.3%) and
      arterial hypertension (33.3%). Thoracentesis was performed in all patients with
      empyema. In one patient with lung abscess an anaerobic microorganism was
      identified. In patients with empyema, cultures were positive in 61.1% of cases,
      with a slight predominance of methicillin-resistant Staphylococcus aureus (27.3%)
      and Prevotella intermedia (18.2%). In patients with both abscess and empyema,
      cultures of the abscess were positive in 44.4% and of the pleural fluid in 33.3%,
      with no predominant microorganism. Empiric antimicrobial therapy was started in
      all patients and later adapted to the antibiotic sensitivity test results.
      Surgery was performed in three patients. Seven patients (23.3%) died during
      admission. The average age of the patients who died was 81.3 years and of those
      who survived was 64.5 years. CONCLUSION: Lung abscess and empyema are infrequent
      diseases in an Internal Medicine ward, affect mostly males and have unspecific
      clinical manifestations. The chest X-ray, computed tomography (CT) and
      thoracentesis were the main diagnostic tests. Most cultures were negative.
      Medical treatment was the most frequent choice, with surgery being used in 10% of
      cases. Older age and multiple associated conditions were associated with a worse
      prognosis.

PMID- 22849908
TI  - [Quality of life, prevalence and profile of patient with malignant neoplasm: a
      case-control population-based study].
AB  - OBJECTIVE: this study had the aim to know the prevalence, profile and the quality
      of life (QoL) of patients with malignant neoplasm in a small Southern Brazilian
      county. Besides largely studied this study is justified due a lack of information
      in the Brazilian population. MATERIAL AND METHODS: This is a cross-sectional
      population-based and case-control study. The data were collected between May to
      August 2008 in all residences of the municipal district and, for each sick
      individual a sex and age matched control were selected. QoL was evaluated through
      WHOQOL-Bref. RESULTS: Fifty eight patients were identified with age between 11 to
      90 years (mean 62.9 +/- 16.5). The prevalence of individuals with malignant
      neoplasm was 1% in the municipal district and those had statistically worst QoL
      when compared with controls. CONCLUSION: This census performed in the district of
      Luzerna/ Brazil showed that 1% of the district population has cancer and the
      results indicate that that specific population has poorer QoL, independently of
      age and tumor kind.

PMID- 22849909
TI  - [Mental health of college students: experience of the university psychiatric
      outpatient clinic of Hospital de Sao Joao].
AB  - The mental health of college students has been raising major awareness, due to
      the increased prevalence and severity of psychiatric disorders in this
      population. Higher education is associated with significant stressors that
      contribute to the development of mental health disturbances, and most college
      students are in the high-risk age group for the emergence of symptoms of major
      psychiatric disorders. Early diagnosis and treatment of these disorders in
      college students are important areas of effort, since they pose a high impact at
      the educational, economic, and social levels. Thus, specifically planned mental
      health services play a major role in the management of this population, should be
      specialized and have easy accessibility. The purpose of this study is to describe
      and characterize the College Students' psychiatric outpatient clinic of the
      Department of Psychiatry, Hospital de Sao Joao.

PMID- 22849910
TI  - [Clinical and epidemiological characteristics of patients with central venous
      catheter colonized by yeasts].
AB  - Among others complications due central venous catheters (CVCs), the blood
      infection (BI) deserves particular attention. The purposes of this study were to
      analyze the clinical and epidemiological characteristics of adult patients using
      CVC; to know the yeast colonization index; and to link it to risk factors for BI.
      Yeasts were investigated in 156 CVCs removed from 91 patients of the Regional
      University Hospital of Maringa from February to August, 2008. Yeast colonization
      was detected in 10.89% of the catheters, which were removed from 15 patients,
      three of them had a fatal hospital yeast infection due to catheter. There was a
      preponderance of male subjects; median age was 66 years and the mean
      hospitalization time was 15 days, greater than that of the non-colonized (p =
      0.003). The mortality rate was significantly greater in this group than among
      those with non-colonized catheters (p = 0.01). Total parenteral nutrition and
      hemodialysis were the risk factors significantly more frequent in this group (p =
      0.002 and 0.001, respectively). The most frequently found yeast was Candida
      parapsilosis. Among the colonized catheters those of double-lumen for infusion
      predominated and the site of insertion was the right subclavian vein. In
      conclusion the colonization by yeasts rate of CVC was 10.89% and 20% of them
      resulted in infection. These results add to higher mortality in patients who CVC
      was colonized by yeasts deserve attention considering the increasing of the
      hospital fungal infections.

PMID- 22849911
TI  - [Bacille Calmette-Guerin adenitis: diagnostic and therapeutic guidelines].
AB  - Bacille Calmette-Guerin (BCG) vaccination is occasionally associated with
      lymphadenitis, called BCGitis, and only rarely can it occur in the setting of
      immunodeficiency. We report six cases of BCGitis admitted to our hospital (2005
      7) for surgical treatment: five were male, in all cases BCG was given at birth;
      median age at presentation was 5.5 months. Three children had spontaneous
      drainage, and one child had two lymph node regions involved (axillary and
      supraclavicular). Five required surgical drainage due to suppuration or
      persistence of lymphadenopathy. The patient with multiple lymph node involvement
      was treated with antimycobacterial therapy for suspected primary
      immunodeficiency, which was never confirmed. Immune function studies were normal
      in all cases. Average follow-up was 15 months. The therapeutical approach of
      suppurative lymphadenitis and the decision to investigate an underlying
      immunodeficiency is not consensual. We think that in the absence of disseminated
      disease an expectant attitude should be adopted.

PMID- 22849912
TI  - [Mushroom poisoning in Portugal].
AB  - The renewed interest in mycology has been reflected in growing use of wild
      mushrooms in culinary, driven by its nutritional, organoleptic and commercial
      value. However, the international scientific literature describes several
      syndromes of poisoning by mushrooms. We live, therefore, a paradigm conducive to
      an increase of mycetism, whose diagnosis requires a high level of suspicion and
      knowledge of clinical profiles. In Portugal, the real dimension of this problem
      is unknown. Although some mycetisms, such as the hepatotoxic syndrome, have high
      morbidity and mortality, their relative incidences are unknown. Add up to the
      shortage of international scientific literature, often outdated and inappropriate
      to clinical practice. In this context, this article provides an updated
      epidemiological and clinical perspective emphasizing a narrative and descriptive
      information on the forms of presentation, differential diagnosis and therapeutic
      approach, with the ultimate goal of the elaboration of a national diagram
      oriented approach to decision-making diagnosis. We analyzed all the clinical
      records of patients admitted into ten hospitals between 1990 and 2008, notified
      with the code 988.1 of GDH (acute poisoning by mushrooms). There were registered
      demographic data, way of presentation, time between ingestion and onset of
      symptoms, the annual distribution, clinical profile, clinical and analytical
      treatment performed and complications. We identified 93 cases of acute poisoning
      by mushrooms, with equal gender distribution and inclusion of individuals of all
      age groups (from 1 to 85 years), but with greater representation from 21 to 50
      years. There was a bimodal seasonal pattern, with a higher peak between September
      and December and a second in the spring. The hepatotoxic profile presentation
      corresponded to 63.4% and 31.7% of the cases to gastroenteritis syndrome. The
      mortality in cases of hepatotoxicity was 11.8%. The developmental profile of the
      rate of prothrombin time (PT), aspartate aminotransferase (AST) and bilirubin,
      was an important setting for diagnosis and prognosis. TGO increases early, always
      within 48 hours, having an essential role in the diagnosis of hepatotoxicity.
      Despite the late elevation of bilirubin, the cases of death revealed that there
      was an earlier increase, reaching higher values, which seems to have a prognostic
      value, to be evaluated with further studies. Finally, we propose a diagram of
      diagnostic performance, considerating the generalized lack of mycological
      diagnosis in Portugal, which emphasizes the need for a careful history, focused
      on quantifying the latency period.

PMID- 22849913
TI  - [Mental health of students of medicine: exploraty study in the Universidade da
      Beira Interior].
AB  - The objective of the present study was to investigate the relations between
      levels of mental health of medical students of the Universidade da Beira
      Interior, from a positive and negative point of view (psychological well-being
      and psychological distress) with sociodemographic factors, year of course and
      psychological support from an health professional. The cross-sectional and
      anonymous study consisted in an online application questionnaire, available
      between February and March of the year 2009, constituted of three sections: a)
      Socio-demographic data b) Mental Health Inventory (MHI) c) Psychological support.
      The results were analyzed on the statistical program SPSS version 17 for Windows
      and the significant results for p <0,05 had been considered. A total of 272
      (49.3%) students answered the questionnaire, of which 215 were female. The basic
      cycle had significant low differences in psychological well-being. The females
      and the third-year of course had large independent and significant negative
      effects on psychological well-being and psychological distress. This study shows
      that 8.6% of the students with levels of mental health below the mean are
      followed by health professionals and 6% do pharmaceutical treatment. About 10% of
      all students already had self-medicated for symptoms related with mental health
      and these had significantly low scores in global Mental Health Inventory. This
      research shows that symptoms of distress appear to be particular important in
      female students and in the 1st and 3rd years and it is necessary to understand
      the causes and the consequences of this situation. Targeted interventions that
      promote psychological well-being during the medical formation, teaching students
      to recognize and deal with symptoms of distress and help them to understand when
      they need aid may be an effective way of dealing with this problem.

PMID- 22849914
TI  - [Nonspecific chronic low back pain and function: a clinical study in a physical
      medicine and rehabilitation consultation].
AB  - OBJECTIVES: Nonspecific chronic low back pain (nCLBP) is a common pathology
      limiting function at different ages. Rehabilitation is not consensual and the
      efficiency is variable. The objective of this study is to describe pain severity
      and disability in activities of daily life (ADL) at the end of conventional
      physical therapy treatment (CPTT). DESIGN: This is a non-randomized cross
      sectional study with 32 consecutive patients, carried out in the central region
      of Portugal during a 6-month period. METHODS: We used the visual analogical scale
      (VAS) for pain and the Oswestry disability index (ODI). Patients self
      administered analgesics and non-steroid anti-inflammatory drugs (NSAIDs) on a
      daily basis, and filled in a form for their characteristics (gender, age and pain
      duration) in the first week after the CPTT. RESULTS: The VAS average value was
      48.7 (18.77) and the total ODI value was 19.6, with a "disability score" of 39%.
      ODI sub-items (intensity of pain 2.88 +- 1.01, lifting 2.78 +- 1.07, social life
      2.19 +-1.12, sitting 2.16 +- 1.00, standing 2.09 +- 1.30) were the most affected.
      Patients took analgesics for 10.6 (12.86) and NSAIDs for 5.2 days (8.99) in a
      month. CONCLUSION: There was a high perception of pain and disability after CPTT,
      which suggests the need to modify the therapeutic approach to achieve more
      effective pain relief and function.

PMID- 22849915
TI  - [Anticoagulation in elderly patients with atrial fibrillation: from the
      guidelines to the daily medical practice].
AB  - BACKGROUND: Atrial fibrillation (AF) is a common medical problem with increasing
      prevalence among the elderly. Warfarin is effective in the prevention of AF
      related-stroke but is often underutilized, especially in high-risk populations,
      like the elderly. OBJECTIVES: To determine, in a group of elderly patients with
      AF, if those treated in-line with the clinical recommendations differ from
      patients who were not, regarding morbidity and mortality and also to determine
      independent predictors of mortality. A second objective was to verify if the
      CHADS2 score is a good predictor of thromboembolic risk in the elderly.
      POPULATION AND METHODS: A total of 161 consecutive elderly patients with AF
      admitted in a single centre were evaluated. Clinical follow-up was available for
      88.4%, with a mean duration of 9 months. RESULTS: Mean age was 80.9 +/- 6.6
      years; 96.3% of the patients had permanent AF, with controlled ventricular rate
      in 56.4%. Previous stroke was verified in 30.4%. Only 37.3% had oral
      anticoagulation at hospital discharge, despite 87.6% had guideline
      recommendation. Cumulative mortality rate in follow-up was 48.4% and the
      thromboembolism rate was 8.1%. We verified that CHADS2 score was a good predictor
      of thromboembolic risk in this population (c-statistic=0.742). Clinical follow-up
      showed that patients treated according with the clinical recommendations were
      more likely to survive (33.33% vs 53.93%; p=0.048). Multivariate analysis showed
      that age >80 years, renal disease, neoplasm and neuropsychic disease as
      independent predictors of mortality (c-statistic=0.83). CONCLUSION: A gap of 50%
      existed between the guideline recommendations and actual practice. The use of
      risk stratification scores can help guide the decision to use anticoagulation in
      older patients with AF. Elderly patients treated according with the clinical
      recommendations had a better prognosis.

PMID- 22849916
TI  - [Bone marrow volunteer donors recruitment in northern Portugal].
AB  - Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat
      a variety of malignant and non-malignant diseases, particularly of the blood and
      immune system. However, as no more than 30% of patients will have HLA-identical
      sibling, much effort has been devoted to the establishment of bone marrow
      registries for HSCT. In 2010, there are more than 15 million bone marrow donors
      and cord blood units in the in the Bone Marrow Donors Worldwide (BMDW) database.
      Participants are 64 stem cell donor registries from 44 countries, and 44 cord
      blood banks from 26 countries. The North Center of Histocompatibility (CHN) is
      one of the three Histocompatibility Centers which made the Portuguese Registry of
      bone marrow donors--National Center of Bone Marrow, Stem Cells and Cord Blood
      Donors (CEDACE). The aim of this paper is to present the first 110000 donors
      recruited by the CHN to the CEDACE. In 2010, the recruited donors throw the CHN
      distribution by age are 14.6%, 38.7%, 37.8% and 8.9%, for the age groups [18;25],
      [25;35], [35;45] and = 45, respectively. The 110000 bone marrow donors recruited
      in the North of Portugal by the CHN are a contribution to the worldwide effort
      that is the BMDW. Young, preferably male donors, should be targeted as
      replacement of the donors who retire because of old age or for other reasons.
      Also, the quest for donors with the so-called unique phenotypes is a challenge
      for all registries. Portuguese areas which show particularly high levels of
      phenotype diversity or those in which alleles of haplotypes underrepresented in
      the registry are identified can and should be targeted for the optimization of
      recruitment strategies.

PMID- 22849917
TI  - [Prevalence and determinants of atypical presentation of acute coronary
      syndrome].
AB  - INTRODUCTION: Knowledge of the characteristics of patients with atypical
      presentation of acute coronary syndromes may contribute to increased sensitivity
      in diagnosis in a given population. The purpose of this study is to quantify the
      prevalence of atypical presentation, to identify its determinants, and to
      describe the presenting symptoms in cases of acute coronary syndrome at the
      emergency department of Hospital Sao Joao, Porto. POPULATION AND METHODS:
      Systematic sample of 288 emergency admissions with a confirmed diagnosis of acute
      coronary syndrome in 2007. Atypical presentation was defined as absence of chest
      pain and/or syncope. RESULTS: The prevalence of atypical presentation was 20.5%
      [95% confidence interval (CI): 16.0 to 25.5], with no important variation by
      gender. It increased with age and was more frequent in cases of ST-segment
      elevation myocardial infarction. In multivariate analysis, atypical presentation
      was associated with age [>70 versus <= 50 years, odds ratio (OR)=3.45; 95%CI:
      1.03-11.61] and it was about four times less likely in the presence of history of
      ischemic heart disease, hypertension, dyslipidemia and smoking. A history of
      heart failure was independently associated with a higher likelihood of acute
      coronary syndrome with atypical presentation (OR = 4.15, 95%CI 1.50-11.46). Among
      the 223 cases who had chest pain or discomfort, a growing, oppressive, prolonged
      (longer than 30 minutes), recurrent and episodic pain prevailed. Among other
      symptoms, dyspnea was the most frequently reported, either as the main symptom in
      cases of atypical presentation or concurrently with typical symptoms. DISCUSSION:
      Factors associated with atypical presentation are consistent with those described
      in other populations. Using routine clinical data allowed access to a large data
      base on a representative sample of patients admitted to the emergency department
      of a third-level hospital that serves a large part of the local urban population.
      In medical records, data are unstandardized and heterogeneous in validity and
      detail. CONCLUSIONS: One fifth of the episodes of acute coronary syndrome have
      atypical presentation, and this proportion is higher in older ages. Previous
      history of ischemic heart disease or its classical risk factors are associated
      with typical symptoms, while heart failure is associated with atypical
      presentation. Presentation in atypical cases is highly variable and does not
      allow the identification of a pattern that would justify lowering the threshold
      for suspicion of acute coronary syndrome.

PMID- 22849918
TI  - [Psychometric hepatic encephalopathy score normalization data for the Portuguese
      population].
AB  - INTRODUCTION: The Minimal Hepatic Encephalopathy (MHE) has been associated to
      changes in life quality and in the aptitude to drive vehicles, to the appearance
      of an explicit form of Hepatic Encephalopathy and to a worst prognosis, including
      a high mortality risk. In this context, the early detection of this condition
      will lead to the reduction of its consequences. The Psychometric Hepatic
      Encephalopathy Score (PHES) consists in five easily applicable and scored tasks
      including the Trail Making Test A and B, the Digit Symbol Test, the Serial
      Dotting Test and the Line Drawing Test. The use of the PHES is recommended by the
      International Society for Hepatic Encephalopathy and Nitrogen Metabolism, for the
      MHE diagnosis and monitorization, as long as local translations and normative
      data are available. The main objective of the present study is the PHES
      normalization for the Portuguese Population. SUBJECTS AND METHODS: The tasks that
      compose the PHES were applied to 115 healthy subjects from four districts of the
      north of Portugal. Variables like age, gender, education years and the profession
      type were study in relation to the obtained results through the use of Student's
      t test and Pearson's correlation. In order to build the normality tables the
      linear regression was used. RESULTS: Age and education years were the independent
      variables more related to the performance on the five tasks. CONCLUSION: The
      availability of the normality tables will allow the MEH diagnosis in Portuguese
      patients with hepatic cirrhosis using an objective and internationally
      recommended method.

PMID- 22849919
TI  - [Cardiovascular risk factors and childhood obesity].
AB  - BACKGROUND: Even in pediatric age, obesity is associated to cardiovascular risk
      factors such as dyslipidemia, high blood pressure and metabolic syndrome, which
      contribute to increased morbidity and mortality in adulthood. AIMS: characterize
      the prevalence of cardiovascular risk factors in obese children and adolescents
      followed in pediatric endocrinology. METHODS: retrospective analysis of cases
      followed between January 1997 and June 2008, with age between two and eighteen
      years. Data analyzed included demographic, epidemiological and clinical
      parameters. BMI z-score, blood pressure, lipid profile and insulinresistance were
      also studied. RESULTS: We evaluated 886 children with a mean age of 9.4 years (SD
      +/- 3.5), 53.6% female and 60% with android type obesity. The lipid profile was
      altered in 42.1% of children. Children with dyslipidemia were younger than
      children without dyslipidemia (9.4 +/- 3.33 vs 9.56 +/- 3.33, p-0.62) and were
      predominantly male (55.2% vs 41.1%, p<0.001). There was not a statistically
      significant difference in z-score between the two groups. High blood pressure was
      found in 32% of cases. In these cases, the mean z-score was significantly higher
      (2.4 +/- 0.54 vs 2.27 +/- 0.49; p-0.001). There was not a statistically
      significant difference in distribution according to age and gender. Metabolic
      syndrome criteria's were found in 5.6% of cases and two children with type two
      Diabetes Mellitus were registered. CONCLUSION: in the studied population we found
      a worrying number of obese children with risk factors for cardiovascular disease.
      In addition to short term complications, the risk of coronary disease and
      atherosclerosis in adulthood is high, so it is essential an early screening and
      surveillance program.

PMID- 22849920
TI  - [Pediatric inflammatory bowel disease: is it still increasing?].
AB  - INTRODUCTION: Crohn's disease (CD), Ulcerative Colitis (UC) and Indeterminate
      Colitis (IC), commonly known as Inflammatory Bowel Disease (IBD) represent a
      heterogeneous group of chronic diseases of unknown origin and varying course,
      diagnosed in pediatric age at 25 to 30% of cases. Epidemiological international
      studies studies show IBD incidence has increased exponentially in industrialized
      nations over the last 50 years. OBJECTIVES: Characterization of the pediatric
      population diagnosed with IBD, followed at medical consultation in
      Gastroenterology at Hospital de Dona Estefania (HDE). MATERIAL AND METHODS:
      Descriptive and retrospective study by consulting the medical files of patients
      diagnosed with IBD followed between 1987 and 2009 (23 years). Clinical,
      radiological and histological criteria were used to define IBD. The following
      variables were studied: sex, family history, race, characterization of IBD, age
      at diagnosis, time from onset of symptoms to diagnosis and clinical presentation.
      Four different periods of time were compared: 1987-1992, 1993-1998, 1999-2004 and
      2005-2009. RESULTS: 100 children were included (51 female), of which 59% are CD,
      38% UC and 3% IC. Family history of IBD was present in 7 cases, with no sex
      difference between UC and CD. During the period of time between 2005-2009, it was
      registered the highest number of new cases (55 total, mean: 11 cases / year) and
      between 1987-1992 the lowest (9, 1.5 cases / year). Time from onset of symptoms
      to diagnosis was highly variable, ranging from 9 months (1987-1992) to 4 months
      (2005-2009). Children's age at the time of diagnosis varied from 14 months to 17
      years, with a mean of 10.5 years. The most common symptoms at time of
      presentation were abdominal pain, diarrhea, and hematochezia. CONCLUSION: IBD are
      a heterogeneous group of diseases, not always easy to diagnose and difficult to
      classify as diagnostic criteria are not always uniform. The results show the
      number of IBD new cases has been rising during the last two decades, mainly CD,
      with no difference between gender. Time from onset of symptoms to diagnosis has
      been decreasing although age at time of diagnosis and clinical presentation has
      showed no difference in the last 20 years.

PMID- 22849921
TI  - [Importance of primary indications for fetal echocardiography proposed by the
      Portuguese Health Department].
AB  - BACKGROUND: Congenital heart disease is the most frequent congenital
      malformation, affecting about 5-8 newborn per thousand live births. Nowadays it
      is possible to do prenatal diagnosis of these conditions with fetal
      echocardiography (EcoF) but because health resources are limited this exam must
      be ordered according to the criteria established by the Portuguese Health
      Department. AIMS: Evaluate the importance of the referral criteria for fetal
      echocardiography attending to the cardiac anomalies identified. To determine
      prevalence and mortality rates in fetus with cardiac anomalies. METHODS:
      Retrospective analysis of the clinical records of 733 fetus to which was
      performed EcoF in the Prenatal Cardiology consultation of a tertiary center of
      Pediatric Cardiology, between 2006 and 2008. Were registered demographic data,
      referral motif, EcoF results and follow-up data. The referral motif was
      classified in two groups: (I) The "Risk Group"--which referral was consistent
      with the Health department indications and this included major causes (family,
      maternal, fetal) and minor causes (other situations), and the "No risk Group"
      (II)--which referral wasn't consistent with those indications. RESULTS: During
      this period were performed 871 fetal echocardiograms to 705 pregnant women. The
      median maternal age was 32 years (15-45 years) and mean gestational age was 26
      weeks (+/- 4 wk). The "Risk group" included 89.5% of the sample. Were identified
      52 cases (7%) with cardiac anomalies in fetal echocardiography: 42 structural
      anomalies, 8 rhythm anomalies and 2 pericardial effusions. These abnormalities
      were distributed as follows: "Risk Group"--family cause (3), maternal cause (3),
      fetal cause (39), minor cause (5) and "No Risk Group" (2). The "Risk Group" had
      more cardiac abnormalities (6.8% vs 0.3%) (p>0.05), specially the "fetal cause
      subgroup" (p<0.05). Were missed on follow up 10 positive cases, there was 3
      medical pregnancy interruptions and 3 children died. Eleven positive cases
      maintain follow-up on Pediatric Cardiology consultation. CONCLUSIONS: Most of the
      cases fulfilled the referral criteria established by the Health Department, but
      there was no statistically significant difference in the prevalence of fetal
      cardiac anomalies in pregnant women with and without risk factors. The fetal
      cause was the best related to the presence of cardiac disease. The prevalence of
      cardiac anomalies and the mortality rate may be underestimated in this sample due
      to the loss of positive cases in the follow-up.

PMID- 22849922
TI  - [Computer-based quality-of-life monitoring in head and neck cancer patients: a
      validation model using the EORTC-QLQ C30 and EORTC- H&N35 Portuguese PC-software
      version].
AB  - Quality of Life is a distinct and important emerging health focus, guiding
      practice and research. The routine Quality of Life evaluation in clinical,
      economic, and epidemiological studies and in medical practice promises a better
      Quality of Life and improved health resources optimization. The use of
      information technology and a Knowledge Management System related to Quality of
      Life assessment is essential to routine clinical evaluation and can define a
      clinical research methodology that is more efficient and better organized. In
      this paper, a Validation Model using the Quality of Life informatics platform is
      presented. Portuguese PC-software using European Organization for Research and
      Treatment of Cancer questionnaires (EORTC-QLQ C30 and EORTC-H&N35), is compared
      with the original paper-pen approach in the Quality of Life monitoring of head
      and neck cancer patients. The Quality of Life informatics platform was designed
      specifically for this study with a simple and intuitive interface that ensures
      confidentiality while providing Quality of Life evaluation for all cancer
      patients. For the Validation Model, the sample selection was random. Fifty-four
      head and neck cancer patients completed 216 questionnaires (108 using the
      informatics platform and 108 using the original paper-pen approach) with a one
      hour interval in between. Patient preferences and computer experience were
      registered. Quality of Life informatics platform showed high usability as a user
      friendly tool. This informatics platform allows data collection by auto-reply,
      database construction, and statistical data analysis and also facilitates the
      automatic listing of the questionnaires. When comparing the approaches (Wilcoxon
      test by item, percentile distribution and Cronbach's alpha), most of the
      responses were similar. Most of the patients (53.6%) reported a preference for
      the software version. The Quality of Life informatics platform has revealed to be
      a powerful and effective tool, allowing a real time analysis of Quality of Life
      data. Computer-based quality-of-life monitoring in head and neck cancer patients
      is essential to get clinically meaningful data that can support clinical
      decisions, identify potential needs, and support a stepped-care model. This
      represents a fundamental step for routine Quality of Life implementation in the
      Oncology Portuguese Institute (IPO-Porto), ORL and C&P department services
      clinical practice. Finally, we propose a diagram of diagnostic performance,
      considerating the generalized lack of mycological diagnosis in Portugal, which
      emphasizes the need for a careful history, focused on quantifying the latency
      period.

PMID- 22849923
TI  - [Family medicine approach to alcohol consumption: detection and brief
      interventions in primary health care].
AB  - AIMS: Evaluate if Brief Interventions are effective to reduce alcohol consumption
      of patients detected as risky consumers; Evaluate if the Physicians' training on
      Brief Interventions to approach alcohol consumption related problems (ARP)
      contributes to change their attitudes towards hazardous and harmful alcohol
      consumers. METHODS: The study had two distinct phases. One phase of
      characterization and assessment of SAAPPQ in a random sample of physicians in the
      District of Lisbon (Phase 1), and another phase with two components: 1) examine
      the perceived attitudes of FPs/GPs towards alcohol consumption of their patients
      before training and again nine months after training, when they were already
      using early identification and brief intervention (EIBI) in their clinical
      practice; 2) determine whether the clinical competences of the FPs/GPs had
      improved in detecting and intervening next to their patients with hazardous or
      harmful alcohol consumption, after the training in Brief Interventions. This
      detection was measured by the AUDIT questionnaire, applied again to the patients
      nine months after the first time (Phase 2). RESULTS AND CONCLUSIONS: Physicians
      in the experimental group at T2 felt more motivated, had higher self-esteem and
      were more satisfied than the control group. There was a positive development of
      the attitude of physicians from the first stage to the second stage, especially
      in the physicians of the experimental group. PATIENTS (T1)--In the sample of
      patients to whom AUDIT was applied, 60% were female and the mean age was 54
      years. It was observed that 21% of the patients had some risky alcohol
      consumption (AUDIT C). Patients (T1 and T2)--In the sample of patients with risk
      consumption, 62% were male and the mean age was 55 years old. Patients followed
      by a physician of the experimental group (compared to patients followed by a
      physician of the control group) had an increase of 54% in the success rate in
      reduction of, at least, one point on the AUDIT, from the first to the second
      stage of the study. In the first stage of the study, the consumption of alcohol
      (in grams) was homogeneous between groups and an average of 193 grams of alcohol
      consumption per week was observed. In the second instance of the study, the
      average alcohol consumption was 145 grams of alcohol per week. This decrease in
      consumption was observed mainly on patients followed by physicians of the
      experimental group. Relationship between physicians and patients--Results
      concerning the relationship between physicians and patients demonstrates that a
      better attitude of physicians in relation to ARP can influence the decrease in
      alcohol consumption of those patients (from the first to the second stage of the
      study).

PMID- 22849924
TI  - [Shaken Baby Syndrome: fact or fiction in Portugal?].
AB  - Shaken Baby Syndrome (SBS) is an unquestionable and current worldwide problem, as
      it is considered one of the most severe forms of child abuse, with significant
      morbidity and mortality among children under one year of age. In Portugal the
      actual incidence of SBS is still unknown and probably undervalued and
      underdiagnosed, but international literature reports incidences between 14 and
      40.5 per 100.000 children a year in several different countries. It is
      classically considered SBS to consist of shaking a child repeatedly and
      violently, inducing a cervical whiplash like movement. Due to the child's
      development stage, this external force of acceleration/deceleration acting on the
      head and cervical musculature may cause several lesions, specially subdural,
      subarachnoid and retinal hemorrhage, and sometimes even bone fractures. However,
      there is no unanimity concerning this trauma mechanism, especially on the
      requirement of direct trauma to the head leading to intracranial lesions, since a
      satisfactory biomechanical model to test it is still lacking. Its diagnosis is
      controversial, difficult and has important legal and family implications, always
      adding an emotional element to it, susceptible of withholding the necessary
      objectivity. In order to substantiate a strong suspicion it is thus mandatory to
      correlate the clinical history, the physical examination and all the diagnostic
      auxiliary exams. Consequences may range from mild to fatal, encompassing the
      child's psychological, cognitive, physical and sensory-motor development, on a
      short or long term basis. Nevertheless, from a global perspective, its prognosis
      is almost always poor. So, education and prevention assume primary importance in
      order to reduce incidence, morbidity and mortality of the SBS. Countries like the
      U.S.A, Scotland, France, Germany, Switzerland, Canada, Estonia and Japan have
      long been interested in studying this syndrome's trauma mechanism and incidence,
      as well as in the development of prevention campaigns and other forms of
      intervention, particularly through education. However, SBS is still greatly
      undisclosed in Portugal, since there are neither epidemiological studies nor
      educational campaigns (or other forms of intervention) on this subject. Thus, the
      aim of this study is to promote reflection and debate on the issue, displaying
      the relevance of studying it and investing in information and training in
      Portugal, in order to prevent and properly diagnose such cases in a timely
      fashion.

PMID- 22849925
TI  - Erectile dysfunction of vascular cause: statistical evaluation on the
      plurimetabolic syndrome's risk factors and their correlation with penile eco
      doppler rates.
AB  - INTRODUCTION: The Plurimetabolic Syndrome is a clustering of vascular risk
      factors (dyslipemia, abdominal perimeter, HTA and impaired glucose tolerance)
      with great importance in the development of cardiovascular disease (CVD) and
      diabetes (DM). CDV and DM are responsible for near 70% of the erectile
      dysfunction causes. Eco-doppler is the first line exam for the evaluation of
      cavernous arterial integrity. METHODS AND MATERIALS: A epidemiologic
      retrospective study and statistic evaluation of the risk factors was made from a
      population of 176 patients who were submitted to penile eco-doppler with a 12 MHz
      BK ultrasound. The procedure was done with 20 to 40 ug of prostaglandin E1 and by
      the some investigator. The criteria of ED of arterial origin were the peak
      systolic velocity (PSV) < 30 cm/seg and the resistance index (IR) < 0,75. For the
      ED of venous-occlusive origin was the peak diastolic velocity (PDV) > 10 cm/seg
      with normal PSV. The control group was the patients without risk factors and with
      normal eco-doppler values. RESULTS/CONCLUSION: The mean age was 49 (17-77) years
      old. The vascular diseases were present in 41% of the population. The venous
      occlusive correspond to 11% of the diagnosis of vascular diseases and 89% to
      arterial origin. The PSV and the IR become lower with the age and the PDV has no
      variation (Spearman correlation coefficient, p < 0,001). The PSV and the IR
      become lower when the risk factors are present and when there are more than one
      risk factor (Mann-Whitney test, p < 0,001). The PDV had no variation. We were not
      able to prove the risk grade of the vascular factors analysed in the PSV and the
      IR (Kruskal-Wallis test, p = 0,2048).

PMID- 22849926
TI  - [Dysmenorrhea in adolescents and young adults: prevalence, related factors and
      limitations in daily living].
AB  - OBJECTIVE: To determine the prevalence of dysmenorrhea, limitations in daily
      living and health care use due to menstrual pain. MATERIAL AND METHODS:
      Observational transversal study of 274 adolescents and young adults (age <= 26)
      who had menstruated in the six months prior to the study, assisted at a Primary
      Health Care Center. Data were obtained by a 24-item anonymous questionnaire,
      which included questions about socio-demographic variables, menstrual cycle,
      presence, duration, severity, treatment and limitations of dysmenorrhea. RESULTS:
      One hundred and seventy-two (62.8%) subjects experienced menstrual pain. Of
      these, 65.7% reported having limitations in their daily activities due to
      dysmenorrhea. The prevalence of limitations in daily living was influenced by the
      presence of additional symptoms (r=0.331; p <0.001), pain intensity (r=0.281; p
      <0.001) and pain duration (r=0.172; p=0.027). The most commonly mentioned
      limitation was anxiety/depression (42.5%). Fourteen of the subjects reported
      missing school or work due to dysmenorrhea. A total of 48 respondents sought
      medical help and 135 reported using therapeutic measures to ease their pain. The
      most common treatments reported for pain treatment included NSAID's (38.5%) and
      oral pills (37.0%). The existence of additional symptoms (r=0.247; p=0.001) and
      the intensity of pain (r=0.160; p=0.039) led to the search for health care.
      CONCLUSIONS: Dysmenorrhea is highly prevalent among this sample of adolescents
      and young adults and is related to absenteeism. Thus, health care providers
      should regularly screen for dysmenorrhea and offer appropriate treatment.

PMID- 22849928
TI  - [Meticilin resistant Staphylococcus aureus and liver abscess: a retrospective
      analysis of 117 patients].
AB  - INTRODUCTION: Liver abscesses are a clinical entity difficult to diagnose and
      treat; therefore, a high index of suspicion is usually important. The majority of
      pyogenic liver abscesses are polymicrobial, with enteric and anaerobic bacteria
      being the most common. Staphylococcus aureus are found in around 7% of the liver
      abscesses, as reviewed in literature. This infection usually results from
      hematogenous dissemination of bacteria that's infecting some other organ. There
      are no published series on this matter, only case-reports. OBJECTIVES AND
      METHODS: In order to investigate the physiopathology, diagnosis and natural
      history of liver abscesses, namely those caused by methicillin-resistant
      Staphylococcus aureus (MRSA), we conducted a retrospective review by studying the
      clinical files of the patients diagnosed with liver abscess/portal pyemia between
      January of 2004 and December of 2009, with a total of 117 patients. RESULTS:
      Fever and abdominal pain were the most common symptoms. Nearly all patients had a
      CT scan for diagnosis. Only 81.2% of patients had microbiological products
      collected. The most common pathogen isolated was Escherichia coli. MRSA was
      isolated in 7.6% of abscesses. Percutaneous drainage combined with antibiotic
      therapy was the most frequent treatment used. All MRSA isolated were susceptible
      to trimethoprim-sulfamethoxazole and vancomycin. The underlying conditions most
      frequently found were biliary diseases, followed by recent abdominal surgery,
      which in turn was the most frequent predisponent condition in MRSA liver
      abscesses. The total mortality rate was 17.9%. One patient died in the group of
      abscesses caused by MRSA. CONCLUSION: MRSA is an important pathogen in hospital
      acquired infections and intraabdominal infections are no exception. We find the
      association with post abdominal surgery very important. These findings have
      remarkable implications in therapeutics, prognosis and investigation.

PMID- 22849927
TI  - [Growth hormone treatment in childhood cancer survivors].
AB  - BACKGROUND: Growth hormone (GH) deficiency is one of the most frequent endocrine
      problems occurring in cancer survivors, particularly when there is a previous
      history of central nervous system (CNS) tumour and submission to radiotherapy
      (RT). MATERIAL AND METHODS: We retrospectively assessed pediatric cancer
      survivors with GH deficiency, submitted to GH treatment from 1988 to 2010 in a
      tertiary level hospital. We analised the following data: sex, age, oncologic
      diagnosis, oncologic treatment, auxology, Tanner puberty stage, final height,
      target height and other associated endocrine problems. We determined the height z
      score difference between the beginning and the end of GH treatment (for patients
      who ended treatment), and between the beginning of GH treatment and the last
      observation (for patients who are currently on treatment), which was defined as
      the dependent variable. SPSS(r) version 17.0 was used for statistical analysis.
      RESULTS: A sample of 18 patients was obtained, 12 male, with a median age of
      cancer diagnosis of six years old. The diagnostics were CNS tumors (n=15) and
      hematologic neoplasia (n=3). Cancer treatment modalities were craniospinal RT
      (n=9), cranial RT (n=4), chemotherapy (n=14) and CNS surgery (n=15). The median
      of time between cancer treatment and beginning of GH treatment was 4 years and 8
      months. Height z-score difference was positive in 12 patients. Statistical
      significant differences between medians and centiles of height z-score difference
      occurred in patients submitted to craniospinal RT (-0.08), cranial RT (0.59) and
      no RT (1.56) (p=0.003, IC 95%). The biggest differences between final height and
      target height (-10 and -11.5 cm) occurred in two patients submitted to
      craniospinal RT, with associated precocious puberty. CONCLUSIONS: Our results are
      consistent with previous studies, which point to a lesser efficacy of GH
      treatment when there is a past history of RT, namely craniospinal RT, and in
      association with precocious puberty.

PMID- 22849929
TI  - [Acute bronchiolitis: a prospective study].
AB  - INTRODUCTION: Bronchiolitis is the most common lower respiratory infection in
      children under 2 years old. Respiratory syncytial virus (RSV) is the most
      frequently involved etiologic agent. AIMS: To identify different viruses causing
      bronchiolitis and try to correlate them with demographic and clinical variables.
      To analyze diagnostic and therapeutic approache. METHODS: We conducted a
      prospective study, between November 2008 and March 2009 (5 months), including
      children < 2 years with bronchiolitis. Screening for RSV, parainfluenza 1-3 and
      adenovirus used immunofluorescence tests and screening for influenza A and B,
      human metapneumovirus (MPvh), human bocavirus (hBoV) and RSV used polymerase
      chain reaction (PCR) techniques. Data were analysed by using SPSS(r). RESULTS: We
      included 78 children with 8.5 months mean age (83% < 12 months), 60% were male.
      The average duration of the disease was 15+5 days. Were on antibiotics 19.2%,
      because of concomitant acute otitis media (10.2%) or bacterial pneumonia (9%).
      53% required hospital admission and the average length of stay was 7 days. Along
      hospitalization 95% of children required supplemental oxygen, 61% intravenous
      rehydration and 22% chest physiotherapy. Viral testing was positive in 59/75
      children: RSV (69.3%), BoVh (22.7%), MPVh (4%), parainfluenza 3 (27%) and
      influenza A (2.6%). Co-infection with two viruses was detected in 23% of
      children. In 88% of children with positive samples for BoVh it has been detected
      RSV infection simultaneously. Children with co-infection (RSV + BoVh) required
      more often hospitalization compared with children infected with RSV alone (80% vs
      60%, p=0.028), without significant differences in oxygen supplementation need and
      length of disease. CONCLUSIONS: RSV was the main etiologic agent and oxygen
      supplementation requirement justified the majority of hospitalizations. There was
      a high rate of co-infection with RSV and BoVh, but without longer disease. BoVh
      infection alone was uncommon.

PMID- 22849930
TI  - [Resilience in institutionalized children and adolescents].
AB  - INTRODUCTION: The concept of resilience refers to the possibility of individuals
      to develop positively when exposed to situations of adversity or stress. This is
      a complex process involving the interaction of vulnerability and protection
      factors. Researching resilience only makes sense when applied to populations
      considered at risk which, simultaneously, present adaptive attributes. That is
      what we find in Child and Adolescent Residential Institutions. There is a rising
      need of research in the area of institutionalized children. A better knowledge of
      these populations allows for the creation of more adapted and efficient
      prevention and promotion health programs. OBJECTIVES: To identify resilience
      factors and their association with psychopathology in children/ adolescents (C/A)
      of three residential institutions in Lisbon. METHOD: Data was collected from a
      sample of children/ adolescents, aged between 6 and 18, who had been
      institutionalized for at least a year, whose legal representatives had signed the
      "informed consent". The three Lisbon institutions were chosen by convenience.
      Children/ adolescents diagnosed with a Pervasive Developmental Disorder (DSM-IV
      TR) were excluded. The instruments used for assessment (Check-list for
      Characterization of the children/adolescents, Institution and Community, and
      Child Behavior Checklist) were completed by the care provider that better knows
      the children/adolescents. RESULTS AND CONCLUSIONS: There are resilience factors
      in those children and adolescents who present no psychopathology which are absent
      in those who have psychopathology. We identified factors that appear to have
      greater resilience preponderance for the protection of children/adolescents,
      namely "positive self-esteem," "talents recognized by others" and "cognitive
      skills". Males have more psychopathology, along with a smaller number of
      resilience factors than females.

PMID- 22849931
TI  - [Periodontal disease, tobacco and preterm delivery].
AB  - Preterm delivery is associated with high mortality and morbility perinatal, being
      the costs dispended by the family and the National Health System with preterm
      newborns extremely high. However, it has been difficult to reduce its incidence
      due to the various factors involved. There is scientific evidence which support
      the relationship between periodontal disease and preterm delivery. There is also
      evidence of tobacco as a risk factor for periodontal disease, even though the
      relationship with preterm delivery is not yet clear. The aims of our study were
      to evaluate, in women in a post-partum period, dental and periodontal status as
      well as the exposure to tobacco and to establish the relationship between these
      two factors with preterm delivery. We performed a case control study with 237
      parturient women from the Department of Obstetrics and Gynecology of Hospital S.
      Joao, E.P.E., during the first 48 hours after birth. A total of 86 gave birth at
      a gestational age under 37 weeks (case group ) and 151 gave birth to term
      newborns with birthweight equal or superior 2500 g (control group). The
      prevalence of some indicators of periodontal disease in the studied population
      was extremely high, namely gingival inflammation and gingival recession, and more
      of 30% had values of probing depth equal or higher than 4 mm significantly. Based
      on these periodontal indicators, only the presence of recession in more than two
      teeth seems to increase the risk of preterm delivery in fivefold (OR = 5,28;
      IC95%: 1,63-17,04). There is a statistically significant association between
      probing depth equal or higher than 4mm and smoking during pregnancy. This
      association might be relevant because 20% of preterm newborns mothers smoked
      during pregnancy and the proportion that stopped smoking during pregnancy in this
      group of mothers was almost half of the number of the control group. Therefore it
      is necessary to embody the information about this thematic in the health
      education, not only in pregnant women but in the general population, alerting for
      the smoking influence in periodontal disease, in pregnant women and in newborns.
      Interventions to help pregnant women to stop smoking should be included, not only
      in prenatal care guidelines used in hospitals, but also by dental medicine
      providers.

PMID- 22849932
TI  - [Empathy in the doctor-patient relationship as viewed by first-year medical
      students: data on validity and sensibility to change of the Jefferson Measure in
      Portugal].
AB  - BACKGROUND AND AIMS: Empathy is a key feature of the doctor-patient relationship.
      Several studies have shown a link between empathic relationships and clinical
      outcomes. However, reports of a decline in empathy over the course of
      undergraduate medical education and medical practice have raised concern among
      medical educators. Our study focuses on the exploration of the temporal stability
      of attitudes towards empathy in first-year medical students. We also aimed to
      characterise this sample regarding attitudes towards empathy and its associations
      with socio-demographic determinants, motives for entering Medicine and
      professional expectations. Finally, we wanted to contribute to the preliminary
      validation in Portugal of the Jefferson Scale of Physician Empathy, students'
      version (JSPE-S), following Hojat's definition of empathy as a predominantly
      cognitive concept. METHODS: We selected a non-randomized sample of 81 first-year
      medical students, in Lisbon. For the evaluation of the motives for choosing
      Medicine as a career, we adapted a questionnaire based on the items reported by
      Vaglum and associates. For self-report assessment of attitudes towards empathy,
      we used a Portuguese translation of the JSPE- -S. Finally, we analysed the
      evolution of empathy-related attitudes through a six-month period that included
      Medical Psychology teaching (given that the curriculum would be expected to raise
      empathy-driven attitudes and skills). RESULTS: The JSPE-S total score increased
      from baseline to follow-up assessments (p=0.001). At the baseline, we found a
      negative correlation between the "status/security" motivation index and the JSPE
      S "standing in patient shoes" component, while there was a positive correlation
      between the "people oriented" motivation index and the JSPE-S "compassionate
      care" factor. Psychometric properties were acceptable for both the JSPE-S and the
      motivation questionnaire. DISCUSSION: In general, our findings support the idea
      that empathy can be learnt in medical schools. This study also provides evidence
      for the validation of the JSPE-S and for the acceptability of an instrument
      assessing motivation for medical school, in Portugal. Albeit weak, the
      correlations between motivational factors and empathy components deserve further
      exploration in research.

PMID- 22849933
TI  - Epidemiology of perinatal depression in Portugal: categorical and dimensional
      approach.
AB  - The aim of the present study was to estimate depressive disorder and
      symptomatology prevalence and incidence in perinatal period in a population-based
      sample. Three-hundred and eighty six Portuguese women (mean age=30.08 years,
      SD=4.21) were interviewed with the Diagnostic Interview for Genetic Studies and
      completed Beck Depression Inventory-II/BDI-II and Postpartum Depression Screening
      Scale/PDSS, in pregnancy and postpartum. OPCRIT polydiagnostic system generated
      ICD-10 and DSM-IV diagnoses. One-month prevalence in pregnancy was of 2.3%/ICD-10
      and 1.3%/DSM-IV; in postpartum it was of 16.6% and 11.7%. Pregnancy incidence was
      of 0%/ICD-10 and .3%/DSM-IV and in postpartum of 7.5%/ ICD-10 and 4.9%/DSM-IV.
      Depression pregnancy point-prevalence found with BDI-II cutoffs ranged from 13.7%
      to 19.4% in pregnancy and from .8% to 13.0% in postpartum and with PDSS from
      14.2% to 17.9% in pregnancy and from 3.9% to 12.7% in postpartum. In the same
      sample, different diagnostic systems generated different prevalence and incidence
      rates. Higher prevalence rates were found using self-reported questionnaires. ICD
      10 generated higher prevalence and incidence rates than DSM-IV.

PMID- 22849934
TI  - [Clinical and therapeutic analysis of type 2 diabetics in Portuguese community
      pharmacies].
AB  - Diabetes is one of the most important chronic diseases in the world. This
      observational study was performed in 7 community pharmacies between October 2002
      and July 2003. OBJECTIVE: Analysis and characterization of demographic, clinical
      and therapeutic aspects of a type 2 diabetes group. METHODOLOGY: Systematic
      selection of 150 patients with questionnaire evaluation. Blood glucose levels,
      blood pressure, body mass index, family history of diabetes and drug intake were
      measured. The data were processed using SPSS. RESULTS: Almost all patients had
      glycemic metabolic decompensation. CONCLUSIONS: identification of therapeutic
      problems and formulation of two study hypotheses: statins could be beneficial to
      the metabolic control of type 2 diabetes. On the other hand oral intake of
      sulphonylureas in association with biguanides could be prejudicial.

PMID- 22849935
TI  - [Nutritional factors associated with dyslipidemia in users of service in primary
      health care].
AB  - BACKGROUND: Dyslipidemias are relevant to public health because are one of the
      major risk factors for Non-Communicable Diseases and Disorders, especially
      cardiovascular diseases. OBJECTIVE: Identify factors associated with
      dyslipidemias on users of Primary Health Care Center. METHODS: Users were
      assessed through the nutritional anamnesis (demographic data, consumption of
      foods and nutrients and morbidity) and anthropometry. Was performed descriptive
      analysis, t-Student, Chi-Square and Mann Whitney tests (p<0.05) and multivariate
      analysis employing the decision tree through CHAID algorithm. RESULTS: It was
      evaluated 105 users, 93.3% were female, mean 52.3 years (+/-13.6) and the
      prevalence of dyslipidemia was 29.8%. Dyslipidemic subjects had higher mean age
      (p=0.057), higher daily consumption of calories (p=0.013) and sugar (p=0.026),
      higher inadequate consumption of eggs (p=0.043) and lower percentage of adequacy
      monounsaturated fatty acids (MUFA) (p=0.007). In contrast, had higher proportion
      of adequacy of lipid (p=0.017), lower mean weight (p=0.044) and lower inadequate
      intake of fatty meat (p=0.005). Multivariate analysis showed that insufficient
      consumption of MUFA (p=0.005) and inadequate intake of lard (p=0.021) were the
      main variables which influenced the presence of dyslipidemia. CONCLUSIONS: The
      results show that important dietary changes for the prevention and control of
      dyslipidemia have not been implemented, demonstrating the importance of
      nutritional interventions aimed at to clarify new dietary strategies, such as
      reduce consumption of sugar and to maintain an adequate consumption of lipid
      fractions.

PMID- 22849936
TI  - [Teaching evidence-based public health to Portuguese medical students: results
      from a questionnaire to assess learning objectives and teaching methods].
AB  - BACKGROUND: The need to teach evidence-based public health to undergraduate
      medical students is clearly established. Following the Bologna reforms under way
      in many European universities and their medical schools, there is a recognised
      need to monitor teaching methods and their results (learning objectives). Within
      this framework, a new Public Health study unit was introduced in the fifth year
      of the Master in Medicine in a Portuguese Medical School (Instituto de Ciencias
      Biomedicas Abel Salazar), in 2007. METHODS: At the end of the final written exam,
      a specifically developed questionnaire was given to all students to be completed
      anonymously. The questionnaire covered the areas of learning objectives and
      teaching methods and formats. RESULTS: After an account of the contents and
      teaching methods used in the course unit, this paper will focus on the
      description and discussion of the results of a questionnaire, used in the
      academic years of 2008/2009 and 2009/2010. All students attending the final exams
      (n = 268) in these two years, succeeded in the study unit. From the 213 valid
      questionnaires it can be concluded that initially proposed learning objectives
      were successfully achieved. Moreover, final reported levels of competency were
      high for most objectives. The students preferred active teaching methods, such as
      group presentation and discussion, compared with passive approaches (eg classical
      lecture). DISCUSSION: This study has methodological limitations, most of which
      derive from the use of a self-completed questionnaire that has not been
      previously validated. Nevertheless, results seem to show the success of the study
      unit, pointing to needed studies in the future. Teaching evidence-based public
      health to undergraduate medical students can be further assessed in the future.

PMID- 22849937
TI  - [Seroprevalence survey of Toscana virus infection in Oporto region].
AB  - Toscana virus (TOSV) endemic in central Italy, has been documented in several
      European countries of the Mediterranean region. It is a neurotropic virus and in
      some of these countries studies to investigate seroprevalence have been done. In
      a recent etiologic study of meningitis we chose 106 of 308 samples to be tested
      for TOSV using a nested RT-PCR assay, and found six (5.6%) cases of meningitis by
      Toscana virus. AIM: To investigate the seroprevalence of antibodies against TOSV
      in a cohort of a population attended in our Hospital. MATERIAL AND METHODS: In
      serum samples collected for routine study we have investigated the presence of
      antibodies for TOSV. The study included samples of patients hospitalized and
      others observed in ambulatory and includes children and adults. Immunocompromised
      patients were excluded. The test was based on the-ELISA technique ((ENZYWELL),
      according to the manufacture instructions, being positive for a cut-off>1.2,
      negative if the cut-off <0.8 and doubtful if the cut-off >0.8 e <1.2. RESULTS:
      334 serum samples arbitrarily were used for seroprevalence study of antibodies to
      TOSV, 304 adults and 30 children. Positive results for anti-TOSV were obtained in
      13 (3.9%) samples; in other 21 the result was doubtful and in those cases it was
      not possible to repeat because we have only one pair of serum and in the
      remaining 300 the result was negative. The positive samples were all from adults,
      8 females and 5 males, 8 (62%) of them were older than 60 years. All children'
      samples were negative for TOSV antibodies. CONCLUSION: We documented a
      seroprevalence of 3.9% to TOSV, namely in adults older than 60 years. Our
      prevalence is lower when compared to other European countries, namely Spain (5
      22%).

PMID- 22849938
TI  - [Hepatitis C in drug addicts: access and treatment compliance].
AB  - Currently, hepatitis C is a serious public health problem. It is estimated that
      there are 180 million people with chronic infection by hepatitis C virus (HCV)
      worldwide and that the prevalence of this infection in the Portuguese population
      ranges between 1 and 1.5%. In Portugal, there are neither up-to-date guidelines
      for treatment, nor recommendations for the diagnosis and management of patients
      with HCV and, in particular, for the endovenous drug users. The present article
      gathers consensus information regarding clinical practice and suggests some
      guidelines to the management and treatment accessibility of drug addicted
      patients with chronic infection by HCV, in Portugal.

PMID- 22849939
TI  - [Self-perception in children with attention-deficit/hyperactivity disorder].
AB  - The Attention-Deficit/ Hyperactivity Disorder (ADHD) is a disorder reflected by
      significant deficits in multiple domains, interfering with the self-perception
      and self-esteem of children. However, international studies that assess the
      relationship between ADHD and self-perception have come to contradictory results,
      and, in Portugal, this is still a little investigated subject. The present work
      aims to assess the self-perception in different areas (scholastic competence,
      athletic competence, physical appearance, behaviour and social acceptance) in
      children with ADHD, comparing them with a control group. This study also tries to
      analyze whether the subtype of ADHD could interfere differently with the self
      perception. We studied 43 children who had a clinical diagnosis of ADHD and 59
      children without this diagnosis. Children with ADHD were divided into different
      subtypes in view of the revised Conners Scales (Portuguese version). The children
      completed the Self-Perception Profile for Children. From the analysis of averages
      comparison, it was found that the group of children with ADHD showed lower values
      in the different domains of self-perception, with a statistically significant
      difference in scholastic and behaviour self-perceptions. Regarding the different
      subtypes of ADHD, the results were not statistically significant, but indicated
      that children perceive themselves differently depending on the subtype. This
      discrepancy was most evident in scholastic competence where children
      predominantly inattentive considered themselves less able than the others. In
      this study, as in the international literature, children with ADHD have an
      scholastic and behavioural self-perception statistically inferior to other
      children of the same age, needing every possible support for a healthy emotional
      development.

PMID- 22849940
TI  - [Toscana virus in the Portuguese population: serosurvey and clinical cases].
AB  - Toscana virus (Phlebovirus genus, Bunyaviridae family) is a neurotropic virus
      which circulates in the Mediterranean Basin. Although Portugal has been the
      second country where its presence was reported, the existence of this virus in
      our country has been referred only sporadically, and there is a lack of knowledge
      regarding the prevalence of antibodies in the population. Thus, the objective of
      this study was to analyse the prevalence of antibodies anti-Toscana virus in the
      human population in our country. Sero-epidemiological investigations were
      performed with indirect immunofluorescence assay (IFA) and enzyme linked
      immunosorbent assay (ELISA) tests. The study population consisted of a control
      population (blood donors, n=150), a population considered at risk (n=236) and a
      population of individuals with symptoms and laboratory diagnostic request for
      vector-borne viruses. The latter population was divided into two groups: those
      individuals with neurological symptoms (n=165) and those without neurological
      symptoms (n=373). We tested sera from a total of 924 individuals. The
      seroprevalence of IgG antibodies in the control population was 2%. In the
      population considered at risk, the prevalence was 3.4%. In the population with
      central nervous system disease, we detected a seroprevalence of 4.2%. For the
      same type of antibodies and in subjects without central nervous system disease,
      the prevalence was 1.3%. Five cases of recent infection (3%) were detected in the
      population with neurological signs. Those infections have been acquired in the
      districts of Faro, Coimbra, Aveiro and Lisbon. The associated clinical diagnoses
      were meningitis, meningoencephalitis and rash. The observed seroprevalences were,
      in general, lower than reported in other endemic countries. Only 5 of the 29 sera
      which gave positive results by IFA and ELISA were confirmed by plaque reduction
      neutralization tests with the Italian strain ISS.Phl.3. This can indicate the
      presence of more than one Toscana virus serotype circulating in Portugal and
      emphasizes the need for more research about this etiological agent in our
      country.

PMID- 22849941
TI  - [Childhood obesity: a health care centre reality].
AB  - INTRODUCTION: Childhood obesity is an important public health issue, especially
      in developed countries, with a multifactorial nature. We purpose to evaluate the
      prevalence of overweight and obesity in a group of children and analyze related
      risk factors. MATERIAL: Study including 207 children aged 5-6 years old enrolled
      in Urban Extension of ACES Ave III - Famalicao. Data were collected from
      connector plugs school health and phone interview of parents. METHODS: Cross
      sectional observational study. Statistical analysis was performed using SPSS
      software and parametric tests were used to verify the statistical significance of
      data, considering statistical significance for p values <0.05. RESULTS: The
      overall prevalence of overweight was 46.9% and obesity 28.5%, and the majority
      were girls. Odds ratio revealed that obesity risk increased with birthweight
      (<2500 g: 1.28; 2500-3000 g: 1.84; 3000 g-3500 g: 1.83; 3500 g-4000 g: 2.00 ),
      the number of hours of sleep (<9 hours: 1.5, 9-10 hours: 1.75;> 10 hours: 1.89),
      the number of hours of television (<2 hours: 1.71; 2-4 hours: 1.81;> 4 hours:
      1.89) and intake of fruit juice as the main drink (not: 1.70; yes: 1.80). The
      obesity risk was higher when parents were overweight and obese (father/mother:
      normal-weight: 1.58 / 1.62; pre-obese: 1.93 / 2.10, obese: 1.86 / 1 79), lived in
      rural areas (urban: 1.67, rural: 1.75) and have basic education (father/mother:
      1st-4th class: 2.20 / 2.58, 5th 9th class: 1.80/ 1.69; 10th-12th class: 1.38 /
      1.65; university: 1.78 / 1.76). There was a association between the number of
      siblings and obesity (zero: 1.84; a: 1.68; two: 1.87; three: 1.75). The physical
      activity acted as a protective factor for obesity (practice: 1.74; not practice:
      1.78). CONCLUSIONS: The results of this study revealed the need for immediate
      implementation of measures involving health professionals, parents and educators.
      Knowledge of various risk factors allows for the adoption of preventive
      strategies to mitigate the impact of childhood obesity.

PMID- 22849942
TI  - [Prevalence of inappropriate urinary catheterization: a preventable risk factor].
AB  - Healthcare-associated infection is an issue with major socio-economic
      implications worldwide. Urinary Tract Infection is a Healthcare-Associated
      infection with a high influence on morbidity and personal impact for patients and
      their families, also has a great economic impact on institutions. The financial
      cost of each infection is difficult to estimate. Urinary catheterization is
      recognized as a main risk factor associated with urinary tract infection.
      However, their use is often essential in providing health care. The frequency
      with which catheters are placed and the duration of catheterization determines
      the magnitude of the risk of infection. If the presence of a urinary catheter is
      inappropriate, then that risk is an avoidable one. The purpose of this study was
      to quantify the presence of inappropriate urinary catheterization in a Medicine
      Department in a general hospital, which involved the analysis of all admitted
      patients to determine the presence of indwelling catheters, on two different
      days, and later by means of review of the medical records, to identify the cases
      that develop urinary tract infection. At the moment of the study there were 160
      inpatients and a bladder catheter was present in 20%. The prescription for
      catheterization was mainly (84,4%) a clinician one. Reason for the permanence of
      the urinary catheter without appropriate indication, was maybe the absence of an
      order to remove the catheter. In our study, we found that 25% of patients with a
      urinary catheter had no clear medical order for it on that day. Another result of
      the study showed that 12 individuals developed urinary tract infection. In this
      12 patients group, five cases had no proper order for a urinary catheter. It
      might be argued that five urinary tract infections were potentially preventable.
      These five potentially avoidable infections represent 41.7% of the urinary tract
      infections diagnosed. This is important data considering the need to improve the
      quality of care as well as all costs associated with the treatment of urinary
      tract infections.

PMID- 22849943
TI  - [The life quality of the people with tuberculosis in observed taking
      administration].
AB  - The World Health Organization assumed, since 1993, Tuberculosis, as a world
      emergency. The control of the disease is implemented by the strategy DOTS (Direct
      Observed Therapy Short Course) through standardized treatments, in administration
      of observed taking (TOD) in order to maximize the success of the treatment and to
      avoid the multi resistance. The monitorization of the problems lived by these
      patients is still little known. The present study is a descriptive and cross
      sectional study. The sample consisted of a 151 users of five Pneumologics
      Diagnostics Centres of the Oporto district (Portugal). The purposes of this study
      was to investigate the life quality of the people with Pulmonary Tuberculosis in
      administration of observed taking and its relation with the descriptive
      variables, socio-economic and clinic variables. The data was collected by: i) a
      bio and a clinical questionnaire, ii) the SF-36. The mean values of the life
      quality swing between 31.3 in the Vitality domain and 68.4 in the Physical Pain
      domain. The younger persons present better levels of life quality in Health in
      General and in the Performance Physical, occurring the inverse in the Social
      Performance. The data suggest a fragile life quality in what concerns the
      Vitality level (31.3), Mental Health (36.7) and Physic Performance (39.7). This
      study makes possible the future focus in the adjustment of the health services to
      the users' necessities, being able to optimize the approval to the treatment,
      increasing the therapeutic success, contributing this way to the disease control.

PMID- 22849944
TI  - [Gd-EOB-DTPA-enhanced magnetic resonance imaging: differentiation between focal
      nodular hyperplasia and hepatocellular adenoma].
AB  - Gadoxetic acid (Gd-EOB-DTPA) is a contrast media used in magnetic resonance
      imaging (MRI) for the detection and characterization of hepatic lesions. It shows
      combined properties of extracellular and biliary excretion, with 50% of the
      administered dose eliminated by the hepatobiliary pathway. One of its
      applications, therefore, is the characterization of focal hepatic lesions,
      including those of hepatocellular nature, such as focal nodular hyperplasia and
      hepatocellular adenoma. Patients with focal nodular hyperplasia (FNH) are usually
      asymptomatic and rarely reveal complications. In other hand, hepatocellular
      adenoma may suffer complications, such as intraperitoneal or intratumoral
      (sometimes massive) bleeding and the possible progression to malignancy.
      OBJECTIVES: To determine the value of MRI with Gd-EOB-DTPA in characterizing
      hepatic lesions, particularly in the differentiation between HNF and AHC.
      MATERIAL AND METHODS: A retrospective study was carried out by investigating
      cases of FNH and HCA referred for MR evaluation with Gd-EOB-DTPA in the
      Department of Radiology of the University Hospitals of Coimbra (HUC) between
      August 2009 and December 2010. We evaluated 32 patients, 24 with FNH and 8 AHC.
      The diagnosis was established by histology, follow-up or agreement between
      imaging methods. In order to evaluate the enhancement after contrast
      administration in the hepatobiliary phase, we calculated the values of Signal-to
      noise ratio (SNR), Contrast-to-noise ratio (CNS) and percentage of enhancement.
      Statistical analysis was performed with SPSS, version 18, and the tests were
      evaluated at a significance level of 5%. RESULTS: The SNR and CNR after contrast
      is significantly different for the two types of lesion (p <0.001 and p = 0.03,
      respectively), with higher values for both parameters in the group of focal
      nodular hyperplasia. As for the % of enhancement, there is a statistically
      significant difference between groups (p = 0.006), again with the FNH group
      presenting higher values. There are significant differences in both groups among
      the studies pre-and post-contrast for the CNR (FNH: p <0.001; adenoma: p =
      0.017), but for the SNR of the lesion the difference manifests in the HNF group
      (p <0,001); the CNR values increase in FNH and decrease in hepatocellular
      adenoma, while for the SNR of the lesion post-contrast values are higher than pre
      contrast, in both groups. CONCLUSIONS: Magnetic resonance imaging with
      hepatospecific contrast is a valuable method for characterization of benign
      hepatic lesions, helping to differentiate FNH from HCA, based on the different
      patterns of uptake and retention of Gd-EOB-DTPA.

PMID- 22849945
TI  - [Adherence to HAART, quality of life and psychopathological symptoms among
      HIV/AIDS infected patients].
AB  - OBJECTIVES: Patient adherence to highly active antiretroviral therapy (HAART) is
      essential to treatment success, and improved quality of life (QoL) and mental
      health have been recognized as important outcomes from the HIV treatment.
      However, very few published research studies have related these domains to HAART
      adherence. The purpose of this study was to examine the association between
      adherence to HAART, QoL and psychopathological symptoms in a sample of HIV
      infected patients, and to identify demographic, clinical and psychological
      predictors of non-adherence. METHODS: A cross-sectional study was conducted in
      the main services/departments of infectious diseases of Portuguese Hospitals. The
      sample consisted of 762 HIV-infected patients. The assessment protocol included
      the Portuguese versions of the WHOQOLHIV-Bref and the Brief Symptom Inventory
      (BSI). RESULTS: Of the 762 patients, 133 (17.5%) reported not to fully adhere to
      HIV medication. Non-adherent patients reported significantly lower QoL. Follow-up
      tests reported significant differences in four of six domains, with the exception
      of Social relationships and Spirituality domains. Regarding psychopathological
      symptoms, there was also a significant effect. Follow-up tests reported a
      significant difference only on psychoticism. In multivariate logistic regression,
      younger individuals, people diagnosed and on medication for longer time, with
      lower CD4+ T cell count, on symptomatic/AIDS stage and with higher scores on
      interpersonal sensitivity, anxiety and psychoticism were more likely to be non
      adherents. CONCLUSIONS: Future studies assessing HAART adherence should consider
      the interplay of demographic and HIV-related variables, as well as psychological
      status. Also, it may help to elicit those people who are at risk for non
      adherence, as well as poorer quality of life and mental health.

PMID- 22849946
TI  - [Multicystic dysplastic kidney. In defense of a conservative experience].
AB  - INTRODUCTION: Multicystic dysplastic kidney (MDK) is one of the most common
      congenital anomalies of the urinary tract and the main cystic renal disease in
      children. Our institution follow-up protocol of MDK uses, as has been performed
      more widely in the last two decades, a conservative attitude. OBJECTIVES: To
      characterize MDK cases followed in our Outpatient Clinic of Pediatric Nephrology,
      evaluate their progress and reflect on the protocol adopted. METHODS: 36 MDK
      patients observed between January 1995 and December 2009 were included in this
      retrospective study and followed-up. In 35 children the diagnosis was the result
      of prenatal ultrasound. All children underwent a systematic protocol, including
      conservative treatment (no surgery) and periodic clinical, laboratory and
      ultrasound evaluation. All children underwent a MAG3 renogram or a 99mTc-DMSA
      renal scintigraphy and a voiding cystourethrography, only repeated in cases of
      vesicoureteral reflux (VUR). RESULTS: Eighteen children (50%) are male. The
      median age of first visit was four weeks. The median of follow-up was 65 months.
      The MDK was in the left kidney in 20 children (56%). The median age of onset was
      10 and six weeks Contralateral nephro-urologic pathology was identified in 10
      cases (28%): seven children with VUR (grade >= IV in three), two with
      ureteropelvic junction obstruction (UPJO) and one with mild pelvic dilatation.
      There was involution of dysplastic kidney in 27 cases (75%), partial in 24 and
      total in three. The involution rate was higher in the first 36 months. There was
      a progressive compensatory hypertrophy of the contralateral kidney, with the
      highest rate in the first two years of life. There was resolution of VUR in five
      of the seven units reflux (three spontaneous and two after ureteral
      reimplantation). The two children with UPJO underwent surgery. There was no
      malignant degeneration and there was not carry out any nephrectomy of dysplastic
      kidney. Urinary infection occurred in nine children (25%), three of which have
      VUR and two with UPJO. There were no cases of hypertension or decreased
      glomerular filtration rate. CONCLUSIONS: The results of this study are generally
      consistent with other casuistics and confirm the fairness of a conservative
      attitude in the approach of children with MDK. This clinical approach is safe,
      with a minimum incidence of complications, with tendency to involution of
      dysplasic kidney being the rule.

PMID- 22849947
TI  - [Wertheim-Meigs operation for cervical cancer and complementary therapy: critical
      analysis of 5 years].
AB  - OBJECTIVES: Review and critical analysis of the Wertheim-Meigs Operations
      performed at our institution in the context of cervical cancer and to assess the
      proportion who underwent treatment with adjuvant radiotherapy (with or without
      chemotherapy) and the main indications. MATERIAL AND METHODS: Retrospective
      review of Wertheim-Meigs operations, conducted in the context of carcinoma of the
      cervix, between 01.01.2005 and 31.12.2010, through consultation with clinical
      processes. It was later performed a descriptive statistical analysis of the
      cases. RESULTS: During this period 119 Wertheim-Meigs Operations were performed.
      Four were excluded: two, for primary indication for adjuvant therapy due to
      histological subtype; two for the inability to exclude invasive disease
      preoperatively and the invasion was not confirmed after surgery. A total of 115
      cases were reviewed and analyzed, and of these 50 (43.5%) underwent complementary
      therapy, the main indication being the presence of lymphovascular invasion in 21
      cases (42% of cases submitted to complementary therapy ). CONCLUSIONS: The mean
      age of patients undergoing radical surgery is 49 years, with stage IB1 most often
      determining its performance. Complementary therapy was performed in 43.5% of
      cases, the main indication being lymphovascular invasion (42%) followed by lymph
      node invasion (16%). Internal audit to the Service is satisfactory, with 16.5%
      surgical complication rate and high technical performance.

PMID- 22849948
TI  - [Association between hyperuricemia and insulin resistance].
AB  - INTRODUCTION: An association between insulin resistance (IR) and cardiovascular
      risk factors has been widely described. However, the association between IR and
      hyperuricemia has been less studied. The objective of this study was to describe
      the prevalence of hyperuricemia in a community sample of Portuguese adults and
      evaluate its association with IR. METHODS: As part of a health and nutrition
      survey, 1370 community participants (852 women and 518 men) were evaluated. IR
      was calculated using the homeostasis model assessment index (HOMA) and IR was
      considered present when HOMA >= 1.85 (the lowest value of the upper quartile of
      HOMA distribution). Hyperuricemia was defined in women as uric acid >= 6.0 mg/dl
      and in men >= 7.0 mg/dl. Unconditional logistic regression models were computed
      and odds ratio (OR) and confidence intervals at 95% (95% CI) were adjusted for
      age, alcohol and tobacco consumption, creatinine levels, body mass index and
      menopausal status. RESULTS: The overall prevalence of hyperuricemia was 12.8%,
      9.9% in women and 17.8% in men (p < 0.001). After adjustment, individuals with
      hyperuricemia had a higher prevalence of IR (OR=1.84 95% CI 1.25-2.73). An
      increased prevalence of IR was associated with increasing levels of uric acid (p
      for trend <0.001). After gender stratification, only hyperuricemic men had a
      higher prevalence of IR (OR=2.17 95% CI 1.24-3.31). Men and women in the upper
      quartile of uric acid had a higher prevalence of IR (OR=2.51 95% CI 1.22-5.16
      and. OR=1.88 95% CI 1.06-3.31, respectively) and a significant trend of
      increasing prevalence of IR with increasing quartiles of uric acid was observed
      (p=0.015 in women and p=0.004 in men). CONCLUSION: Hyperuricaemic men had a
      higher prevalence of IR. Both men and women in the upper quartile of uric acid
      distribution showed positive associations with IR and an increased prevalence of
      IR with increasing quartiles of uric acid was observed.

PMID- 22849949
TI  - [Venous thromboembolism's risk assessment: rationale, objectives, and methodology
      -the ARTE study].
AB  - Venous thromboembolism is a frequent clinical condition with high impact on both
      morbidity and mortality. Venous thromboembolism risk is particularly high in
      hospitalized patients as well as in oncologic patients, being a factor of poor
      prognosis for the oncologic disease. Several clinical studies have shown the need
      to develop effective hospital strategies using a systematic and individualized
      assessment of venous thromboembolism risk, and additionally to optimize the
      institution of prophylaxis treatment and its proper use in the context of in
      hospital and outpatient management. The ARTE national study is a non
      interventional, multicentre, prospective study which is divided in two phases. In
      the first phase patients are followed in the hospital; in the second phase
      patients are followed in ambulatory context for a period of 6 months after
      discharge. Four thousand patients will be included, equally distributed over
      medical, surgical, oncologic and orthopaedic patients. Data will be collected
      from the patient's clinical files and through direct clinical evaluation of risk
      factors for venous thromboembolism, in the departments of medicine, oncology,
      surgery, and orthopaedics of the participating centres. The main objectives of
      the study are to assess the risk profile of venous thromboembolism of the study
      population using a risk assessment model adapted from the Caprini and Khorana et
      al models, and the validation of the score for the Portuguese population.
      Simultaneously, the secondary objectives are as follows: to determine the
      proportion of patients with venous thromboembolism risk, according to the risk
      assessment model, that are doing prophylaxis; to determine the duration of
      prophylaxis during the hospitalization; to determine the proportion of patients
      doing long-term prophylaxis, at the moment of the discharge; to determine the
      incidence of thromboembolic events (deep venous thrombosis; stroke; pulmonary
      thromboembolism; transient ischemic attack), haemorrhagic events (major and minor
      haemorrhages) and death at 6 months after discharge. Each patient will be
      contacted by telephone at 3 and 6 months after discharge, in order to assess the
      occurrence of thromboembolic and haemorrhagic events, as well as any readmission.
      This article describes the ARTE study's rationale, objectives, and methodology.

PMID- 22849950
TI  - [The Alvarado score validation in diagnosing acute appendicitis in children at
      Braga Hospital].
AB  - INTRODUCTION: Acute appendicitis (AA) is the leading cause of emergency abdominal
      surgery in children. The diagnosis is essentially clinical, but some
      methodologies, such as Alvarado score (AS), have been developed in order to avoid
      non-therapeutic laparotomy (15-30%). AS >= 5 or 6 is compatible with AA and is an
      indication for the patient to remain on observations, if AS >= 7 a laparotomy
      procedure may be indicated. OBJECTIVE: To validate the AS for the AA diagnosis of
      children admitted at Braga Hospital. METHODS: A validation study of diagnostic
      method (AS) using the histological examination as a gold standard. The study
      population consisted of 192 children (4-17 years) with abdominal pain that
      underwent appendectomy in the last 20 months (December 2008 to July 2010). It was
      determined the values of sensitivity (S), specificity (Sp), positive predictive
      value (PPV), negative predictive value (NPV), likelihood ratio (LR) and the ROC
      curve for three different cut-off points (SA =5, 6 and 7). RESULTS: We found that
      as the cut-off point of AS decreases progressively the sensitivity and
      specificity increases and reduces the VPN and VPP. Assuming a cut-off value of 5,
      only 18 children would be false negatives, instead of the 67 children if the cut
      off point was 7 points. The analysis of ROC curves demonstrated a greater area
      under the curve for a cut-off equal to or greater than 5 (AUC = 70%). DISCUSSION:
      We recommend using a cut-off value of 5 points, since only 18 children with AA
      were initially classified as appendicitis unlikely, this value would increase to
      67 patients for the SA value of >= 7. The AS is a valuable tool in screening
      children with abdominal pain for the diagnosis of AA. Nonetheless the diagnosis
      and final decision must be based on clinical and systematic reassessment of
      patients.

PMID- 22849951
TI  - [Job satisfaction among the professionals of AceS Baixo Vouga II].
AB  - Job satisfaction is a measure of quality of life at work and is related to
      emotional states. The interest for this theme is increasing and, in the last
      years, many studies have attempted to demonstrate its relation with professional
      performance. Primary care professionals are in the first line of the Servico
      Nacional de Saude (SNS). Therefore, it is necessary that they feel satisfaction
      with their jobs, in order to perform the tasks with the quality required. Several
      factors seem to have impact in the satisfaction of these professionals, such as
      payment, promotion, recognition from supervisors and peers, physical conditions
      at work and available resources, opportunities for personal development, among
      others. Insatisfaction may lead to absentism and in the limit to job quit. The
      main objective of this work is to study job satisfaction among the professionals
      working at the health centers of ACeS Baixo Vouga II, namely, the relationship
      between job characteristics and job satisfaction and between job characteristics
      and considering job quit as a serious option. All the professionals working in
      the four health centers were inquired. Results show that job characteristics are
      defined by six dimensions: leadership and supervision, task characteristics and
      autonomy, payment, personal and professional development and promotion, peers and
      relations inside the organization and work environment. Globally, payment and
      opportunities for personal and professional development and promotion are
      perceived at low level by all the professional groups. Results also show that
      there are differences by gender and professional groups regarding job
      satisfaction and the will to quit job. Considering the specificity of the tasks
      performed by these professionals, measures should be taken in order to improve
      job satisfaction in the Portuguese health centers.

PMID- 22849952
TI  - n-3 Fatty acids inhibit transcription of human IL-13: implications for
      development of T helper type 2 immune responses.
AB  - Fish oil supplementation during pregnancy has been associated with lower levels
      of cord blood IL-13, suggesting that the administration of n-3 fatty acids may
      attenuate the development of allergic disease. The present study aimed to
      investigate the mechanism by which n-3 fatty acid administration influences the
      production of IL-13. Pregnant BALB/c mice were fed nutritionally complete high
      fat diets (15 %, w/w) with an n-3 fatty acid-enriched (DHA 1 %, w/w) or control
      diet (0 % DHA) immediately following delivery. Pups were exposed during suckling
      and weaned to the maternal diet for the remainder of the study. The production of
      IL-13, IL-4, IL-10 and interferon-gamma from the splenocytes of ovalbumin (ova)
      sensitised animals was assessed following in vitro ova stimulation or
      unstimulated conditions. Human T helper type 2 (Th2) cells were mitogen
      stimulated in the presence or absence of DHA (10 MUM) and assessed for IL-13 and
      IL-4 expression using intracellular flow cytometry. The influence on
      transcriptional activation was studied using a human IL-13 promoter reporter
      construct and electromobility shift assay. Ova-activated splenocytes from DHA-fed
      mice produced less IL-13 (57.2 (se 21.7) pg/ml) and IL-4 (7.33 (SE 3.4) pg/ml)
      compared with cells from the animals fed the control diet (161.5 (SE 45.0), P<
      0.05; 33.2 (SE 11.8), P< 0.05). In vitro, DHA inhibited the expression of IL-13
      protein from human Th2 cells as well as transcriptional activation and binding of
      the transcription factors cyclic AMP response element binding and activating
      transcription factor 2 to the human IL-13 promoter. These data indicate the
      potential of n-3 fatty acids to attenuate IL-13 expression, and suggest that they
      may subsequently reduce allergic sensitisation and the development of allergic
      disease.

PMID- 22849953
TI  - Theory of mind performance in children correlates with functional specialization
      of a brain region for thinking about thoughts.
AB  - Thinking about other people's thoughts recruits a specific group of brain
      regions, including the temporo-parietal junctions (TPJ), precuneus (PC), and
      medial prefrontal cortex (MPFC). The same brain regions were recruited when
      children (N=20, 5-11 years) and adults (N=8) listened to descriptions of
      characters' mental states, compared to descriptions of physical events. Between
      ages 5 and 11 years, responses in the bilateral TPJ became increasingly specific
      to stories describing mental states as opposed to people's appearance and social
      relationships. Functional activity in the right TPJ was related to children's
      performance on a high level theory of mind task. These findings provide insights
      into the origin of neural mechanisms of theory of mind, and how behavioral and
      neural changes can be related in development.

PMID- 22849954
TI  - Older adults living with osteoarthritis: examining the relationship of age and
      gender to medicine use.
AB  - Osteoarthritis (OA) in older adults is a prevalent chronic condition associated
      with substantial pain and disability. Oral analgesic use is a central component
      of symptom management. Medication use in this population, however, is complex and
      must balance the need for symptom control with drug safety concerns. Our study
      focus was to illustrate and discuss the variability in the medications used to
      manage OA-related symptoms. We analysed data from a sample of community-dwelling
      persons aged 55 and older with hip or knee arthritis to examine social and
      medical factors associated with reported variation in OA drugs. A key finding is
      that drug types used by OA patients vary by age and gender, independent of
      disease, and medical and social context. Possible explanations related to patient
      and professional preferences are considered.

PMID- 22849955
TI  - Transcatheter aortic valve implantation (TAVI): risky and costly.

PMID- 22849957
TI  - Psychological distress and death from cardiovascular disease.

PMID- 22849956
TI  - Association between psychological distress and mortality: individual participant
      pooled analysis of 10 prospective cohort studies.
AB  - OBJECTIVE: To quantify the link between lower, subclinically symptomatic, levels
      of psychological distress and cause-specific mortality in a large scale,
      population based study. DESIGN: Individual participant meta-analysis of 10 large
      prospective cohort studies from the Health Survey for England. Baseline
      psychological distress measured by the 12 item General Health Questionnaire
      score, and mortality from death certification. PARTICIPANTS: 68,222 people from
      general population samples of adults aged 35 years and over, free of
      cardiovascular disease and cancer, and living in private households in England at
      study baseline. MAIN OUTCOME MEASURES: Death from all causes (n = 8365),
      cardiovascular disease including cerebrovascular disease (n = 3382), all cancers
      (n = 2552), and deaths from external causes (n = 386). Mean follow-up was 8.2
      years (standard deviation 3.5). RESULTS: We found a dose-response association
      between psychological distress across the full range of severity and an increased
      risk of mortality (age and sex adjusted hazard ratio for General Health
      Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to
      1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26;
      P<0.001 for trend). This association remained after adjustment for somatic
      comorbidity plus behavioural and socioeconomic factors. A similar association was
      found for cardiovascular disease deaths and deaths from external causes. Cancer
      death was only associated with psychological distress at higher levels.
      CONCLUSIONS: Psychological distress is associated with increased risk of
      mortality from several major causes in a dose-response pattern. Risk of mortality
      was raised even at lower levels of distress.

PMID- 22849958
TI  - A randomized clinical trial of living donor nephrectomy: a plea for a
      differentiated appraisal of mini-open muscle splitting incision and hand-assisted
      laparoscopic donor nephrectomy.
AB  - A randomized controlled trial was designed to compare various outcome variables
      of the retroperitoneal mini-open muscle splitting incision (MSI) technique and
      the transperitoneal hand-assisted laparoscopic technique (HAL) in performing
      living donor nephrectomies. Fifty living kidney donors were randomized to MSI or
      HAL. Primary endpoint was pain experience scored on a visual analogue scale
      (VAS). After MSI living donors indicated lower median (range) VAS scores at rest
      than HAL living donors on postoperative day 2.5 [10 (0-44) vs. 15 (0-70), P =
      0.043] and day 3 [7 (0-28) vs. 10 (0-91), P = 0.023] and lower VAS scores while
      coughing on postoperative day 3 [20 (0-73) vs. 42 (6-86), P = 0.001], day 7 [8 (0
      66) vs. 33 (3-76), P < 0.001] and day 14 [2 (0-17) vs. 12 (0-51), P = 0.009]. The
      MSI technique also resulted in reduced morphine requirement, better scores on
      three domains of the RAND-36, reduced costs and reduced CRP and IL-6 levels. The
      HAL technique was superior in operating time and postoperative decrease of
      hemoglobin level. The MSI technique is superior to the HAL technique in
      performing living donor nephrectomies with regard to postoperative pain
      experience. This study reopens the discussion of the way to go in performing the
      living donor nephrectomy.

PMID- 22849959
TI  - Microwave characterisation of carbon nanotube powders.
AB  - We have used a 3-GHz microwave host cavity to study the remarkable electronic
      properties of metallic, single-walled carbon nanotubes. Powder samples are placed
      in its magnetic field antinode, which induces microwave currents without the need
      for electrical contacts. Samples are shown to screen effectively the microwave
      magnetic field, implying an extremely low value of sheet resistance (< 10
      MUOmega) within the graphene sheets making up the curved nanotube walls.
      Associated microwave losses are large due to the large surface area, and also
      point to a similar, very small value of sheet resistance due to the inherent
      ballistic electron transport.

PMID- 22849961
TI  - Renal toxicity associated with antiretroviral therapy.
AB  - Renal disease is becoming an increasingly prevalent comorbidity in patients with
      human immunodeficiency virus (HIV) infection. The increase in life expectancy
      following the introduction of highly active antiretroviral therapy (HAART) and
      the long-term development of metabolic complications (such as diabetes and
      dyslipidaemia), hypertension, and vascular diseases can contribute to the
      increasing frequency in the recognition of renal impairment in HIV-infected
      patients. Some antiretroviral agents, and particularly tenofovir, have been
      associated with nephrotoxic drug effects, including decline in glomerular
      filtration rate, proximal tubular damage, and acute kidney injury. The occurrence
      of clinically evident renal toxicity in patients treated with HAART seems to be
      very low, but glomerular or tubular subclinical dysfunction may occur more
      frequently. Therefore, careful clinical and laboratory monitoring for the early
      recognition of renal abnormalities is recommended for all subjects receiving
      antiretroviral treatment. In this article, the current knowledge about the
      nephrotoxic effects of antiretroviral agents has been reviewed, and an algorithm
      for screening and management of HAART-related kidney disease is proposed in the
      light of the most recent clinical studies and international guidelines.

PMID- 22849960
TI  - A pilot, prospective, open-label simplification study to evaluate the safety,
      efficacy, and pharmacokinetics of once-daily lopinavir-ritonavir monotherapy in
      HIV-HCV coinfected patients: the MONOCO study.
AB  - BACKGROUND: A safe, effective, easy-to-dose antiretroviral therapy that minimizes
      hepatic complication risk is essential in optimizing HIV-HCV treatment.
      Nucleoside-sparing boosted protease inhibitor monotherapy may achieve this goal.
      METHODS: A prospective, open-label pilot simplification study of once-daily
      lopinavir/ritonavir (LPV/r) monotherapy in HIV-HCV coinfected patients was
      conducted in patients on HAART with undetectable HIV RNA for >=6 months. The
      primary outcome was maintenance of HIV RNA<50 copies/mL through week 48. HIV RNA,
      immune measures, metabolic markers, and pharmacokinetics were assessed. RESULTS:
      Twenty participants received once-daily LPV/r monotherapy. Mean baseline age was
      46.9 years and CD4 467 cells/L. By per protocol analysis, 71.4% (95% CI, 45.4
      88.3) remained on once-daily LPV/r monotherapy with virologic suppression at week
      48. Virologic breakthrough (HIV RNA>50 copies/mL on 2 consecutive measures)
      occurred in 7 patients (mean standard error [SE] time to breakthrough, 38.3 [4.8]
      weeks). Resuppression occurred with improved adherence in 2 participants and
      improved adherence plus addition of nucleosides in 2 others. LPV C min was <1
      mg/L in 8 patients and was associated with virologic breakthrough in 2 cases but
      with no development of resistance. No clinically significant changes in CD4,
      lipids, or glucose were noted. Three participants developed transient>=5-fold
      liver enzyme elevations. None of 9 severe adverse events were LPV/r- or liver
      related. Six discontinued participation for withdrawal of consent (n=1), poor
      adherence (n=3), or drug intolerance (n=2). CONCLUSIONS: Once-daily LPV/r
      monotherapy in HIV-HCV coinfected individuals offers a safe and effective
      approach to the management of the HIV infection, with a predictable
      pharmacokinetic profile.

PMID- 22849963
TI  - Alterations in cerebrospinal fluid chemokines are associated with maraviroc
      exposure and in vivo metabolites measurable by magnetic resonance spectroscopy.
AB  - BACKGROUND: Cerebrospinal (CSF) fluid biomarkers may be a useful tool for
      assessing the cerebral effects of antiretroviral therapy. OBJECTIVE: The aim of
      the study was to investigate the relationship between 4 CSF chemokines with
      maraviroc exposure and cerebral metabolite ratios (CMR) measured by magnetic
      resonance spectroscopy (1H-MRS) in HIV-infected individuals following maraviroc
      intensification. METHODS: CSF concentration of maraviroc and 4 chemokines (MCP-1,
      IP-10, MCP-4, and MIP-1beta), plasma concentration of maraviroc pre-CSF
      assessment, and right basal ganglia CMR were assessed in 12 male HIV-infected,
      neuro-asymptomatic adults after 14 days of antiretroviral therapy intensification
      with maraviroc 150 mg twice daily. The relationship between CSF analytes with
      both CMRs and plasma and CSF maraviroc concentrations were examined using
      Spearman correlation coefficient. RESULTS: Twelve subjects completed study
      procedures with baseline values as follows: mean (SD) age 42 (8) years, CD4+ cell
      count 503 (199) cells/uL, and plasma HIV RNA<50 copies/mL in most subjects. Mean
      (range, pg/mL) chemokine concentrations were IP-10, 1242 (190-8073); MCP-4, 6.52
      (1-18); MCP-1, 702 (201-1618); and MIP-1beta, 42 (5-153). IP-10, MCP-4, and MIP
      1beta were significantly associated with CMRs in the right basal ganglia with (1)
      lower concentrations of IP-10 correlating with higher N-acetyl aspartate to
      creatine ratios (NAA/Cr) and (2) higher concentrations of MCP-4 and MIP-1beta
      correlating with higher myoinositol to creatine (mI/Cr) ratios. There were no
      significant associations with MCP-1. Finally lower concentrations of IP-10 were
      significantly associated with higher maraviroc plasma trough concentration (r=
      0.629, P=.028) but not CSF concentration (r=-0.308, P=.331). CONCLUSION: We
      hypothesize that the relationship between IP-10, MCP-4, and MIP-1beta with
      maraviroc exposure and CMRs may be associated with a direct cerebral effect of
      maraviroc.

PMID- 22849962
TI  - Bone effects of rosiglitazone in HIV-infected patients with lipoatrophy.
AB  - OBJECTIVES: Thiazoledinediones increase limb fat in HIV+ patients with
      lipoatrophy. However, their use in the general population has been associated
      with bone loss and fracture. We sought to determine the effects of rosiglitazone
      on bone metabolism in HIV-infected patients. METHODS: HIV+ patients with
      lipoatrophy were randomized to rosiglitazone versus placebo for 48 weeks in a
      double-blind, placebo-controlled trial. Limb fat, bone mineral density (BMD),
      bone formation markers (procollagen type 1 amino-terminal propeptide [P1NP],
      osteocalcin [OC]) and bone resorption markers (C-terminal telopeptide of type I
      collagen [CTX]) were measured, along with receptor activator for nuclear factor
      kappa beta ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines.
      RESULTS: Seventy-one subjects were randomized to rosiglitazone or placebo: 17%
      female and 51% white. Total BMD did not change significantly in either group. In
      the rosiglitazone group, P1NP showed statistically significant decreases at 24
      and 48 weeks; however, changes compared to placebo were only significant at 24
      weeks. OC decreased significantly in the rosiglitazone group at 24 weeks, but
      there were no between-group differences. CTX, RANKL, or OPG did not change for
      either group. Multivariable regression within the rosiglitazone arm showed P1NP
      changes were inversely associated with limb fat changes, protease inhibitors, and
      tenofovir use. CONCLUSION: Rosiglitazone use was associated with decreased bone
      formation, but it did not alter bone resorption or total BMD. The increase in
      limb fat that accompanies rosiglitazone use appears to be associated with
      decreased osteoblast activity. Further studies are needed to determine the effect
      of thiazoledinediones on bone health in HIV-infected persons.

PMID- 22849965
TI  - Strategies for improving patient safety culture in hospitals: a systematic
      review.
AB  - PURPOSE: To determine the effectiveness of patient safety culture strategies to
      improve hospital patient safety climate. DATA SOURCES: Electronic search of the
      Cochrane Library, OVID Medline, Embase, CINAHL, proQuest and psychinfo databases,
      with manual searches of quality and safety websites, bibliographies of included
      articles and key journals. STUDY SELECTION: English language studies published
      between January 1996 and April 2011 that measured the effectiveness of patient
      safety culture strategies using a quantitative measure of patient safety climate
      in a hospital setting. Studies included were randomised controlled trials (RCTs),
      non-RCTs, controlled before and after studies, interrupted time series and
      historically controlled studies. DATA EXTRACTION: Data extraction and critical
      appraisal were conducted by two independent reviewers. Study design,
      intervention, level of application, setting, study participants, safety climate
      outcome measures and implementation lessons were extracted from each article.
      RESULTS OF DATA SYNTHESIS: Over 2000 articles were screened, with 21 studies
      meeting the inclusion criteria, one cluster RCT, seven controlled before and
      after studies, and 13 historically controlled studies. There was marked
      methodological heterogeneity amongst studies. Impacts of 11 different strategies
      were reported. There was some evidence to support that leadership walk rounds
      (p=0.02) and multi-faceted unit-based programmes (p < 0.05) may have a positive
      impact on patient safety climate. CONCLUSIONS: Despite strong face validity for a
      variety of patient safety culture strategies, there is limited evidence to
      support definitive impacts on patient safety climate outcomes. Organisations are
      advised to consider robust evaluation designs when implementing these potentially
      resource intensive strategies.

PMID- 22849966
TI  - A laboratory study on the effect of Paraiotonchium autumnale parasitism on the
      longevity of Musca autumnalis.
AB  - Paraiotonchium autumnale (Nickle) (Tylenchida: Iotonchiidae) causes parasitic
      sterilization in female Musca autumnalis DeGeer (Diptera: Muscidae). In addition
      to sterilization, P. autumnale causes physiological and behavioural changes
      within its host. However, there have been no records of reduced host lifespan in
      this system. Studies were conducted in 2009 and 2010 with wild M. autumnalis
      collected as larvae from cow dung pats from Browns Valley, California, USA. Field
      collected larvae were reared to adulthood and flies of the same eclosion dates
      were caged together, regardless of whether or not they were parasitized. Dead
      flies were collected daily, and parasitism status was confirmed by dissection.
      Due to the very different effects of P. autumnale-parasitism on male versus
      female face flies, flies were analysed separately by sex. Kaplan-Meier analysis
      revealed a non-significant difference in longevity between non-parasitized and
      parasitized flies for female and male flies in 2009. In 2010, however,
      significant differences (P < 0.05) were found between parasitized and non
      parasitized female and male flies. In 2010, the median time to death for non
      parasitized female flies was 20 days and 15 days for parasitized females. The
      2010 median survival time for non-parasitized male flies was 33 days and 15 days
      for parasitized males. This is a parasite-mediated cost to the host that has not
      been recorded previously. Based on our results and results from another published
      study we suggest that the potential for sterilizing parasites to alter host
      longevity is condition dependent.

PMID- 22849964
TI  - Efficacy of raltegravir versus efavirenz when combined with
      tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: week-192
      overall and subgroup analyses from STARTMRK.
AB  - We compared 4 years of antiretroviral therapy with tenofovir/emtricitabine and
      either raltegravir or efavirenz from the ongoing STARTMRK study of treatment
      naive HIV-infected patients. Through 192 weeks, raltegravir produced durable and
      consistent viral suppression and immune restoration compared with efavirenz
      irrespective of baseline demographic and prognostic factors, including in
      patients with high viral loads.

PMID- 22849967
TI  - A controlled before and after study to evaluate a patient and health professional
      partnership model towards effective medication reconciliation.
AB  - Preventable medication errors impact substantially on the Australian healthcare
      system. Where 'poor communication of medical information at transition points is
      responsible for as many as 50% of all medication errors', a leading contributor
      for this type of medication error is lack of consumer knowledge about medicines
      information. This study was aimed at designing and testing the effectiveness of a
      consumer-healthcare professional partnership model towards effective medication
      reconciliation. This model aims to empower consumers about their medicines
      information, so that they would contribute more effectively to medication
      reconciliation and thereby minimise medication errors occurring at transition
      points. Components of this model were informed by qualitative data gleaned from
      patient opinion surveys, focus group sessions involving nurses, doctors and
      pharmacists working at the hospital and results of a literature search of
      medication safety tools. Programme development was informed by health improvement
      approaches centred on a Plan-Do-Study-Act cycle. Evaluation for effectiveness was
      conducted within a framework of a controlled before and after study. RESULTS:
      revealed that there was a 1.4-fold increase in the reporting rate of pharmacists
      intervention. The study could not demonstrate that the designed intervention was
      effective in minimising near-misses. However, there is statistically
      insignificant reduction in errors for patients that were correctly exposed to the
      intervention. Anecdotal evidence suggests there is utility for a patient
      population keen to claim greater ownership of their medicines information.
      Further, we advocate that patient education about medicines and the establishment
      of a consumer-healthcare professional model occur prior to ward admission.

PMID- 22849968
TI  - Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi
      ethnic areas of England.
AB  - The aim of this study was to estimate the amount of childhood hepatitis B virus
      transmission in children born in the UK, a very low-prevalence country, that is
      preventable only by universal hepatitis B immunization of infants. Oral fluid
      specimens were collected from schoolchildren aged 7-11 years in four inner city
      multi-ethnic areas and tested for the presence of antibody to hepatitis B core
      antigen (anti-HBc). Those found positive or indeterminate were followed up with
      testing on serum to confirm their hepatitis B status. The overall prevalence of
      anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The
      estimated average annual incidence of hepatitis B was estimated to be 29.26/100
      000 children (95% CI 16.00-49.08). The total incidence that is preventable only
      by a universal infant immunization programme in the UK was estimated to be
      between 5.00 and 12.49/100 000. The study demonstrates that the extent of
      horizontal childhood hepatitis B virus transmission is low in children born in
      the UK and suggests that schools in the UK are an uncommon setting for the
      transmission of the virus. Targeted hepatitis B testing and immunization of
      migrants from intermediate- and high-prevalence countries is likely to be a more
      effective measure to reduce childhood transmission than a universal infant
      immunization programme.

PMID- 22849969
TI  - Enhanced behavioral response to serotonin-related agonists in postweaning protein
      malnourished mice.
AB  - We investigated whether postweaning protein malnutrition (PM) affects
      serotonergic systems. Mice were fed a PM diet or normal protein (control) diet
      from weaning (21 d of age). Twenty days later, we tested for behavioral effects
      of the selective serotonin (5-HT)(1A) receptor agonist 8-hydroxy-N,N-dipropyl-2
      aminoteralin (8-OH-DPAT) and the 5-HT releaser d-fenfluramine. The number of head
      weaving responses induced by 8-OH-DPAT or d-fenfluramine in the PM mice was
      significantly increased compared with the control diet group. The effects of 8-OH
      DPAT and d-fenfluramine were blocked by pretreatment with the selective 5-HT(1A)
      receptor antagonist WAY-100635 (0.01 mg/kg). However, postpubertal (56 d of age)
      mice fed with the PM diet did not show an enhancement of the 8-OH-DPAT-induced
      head weaving response. These results indicate the occurence of a supersensitivity
      of postsynaptic 5-HT(1A) receptor in the postweaning PM group. Moreover, they
      highlight the postweaning stage as a vulnerable period to malnutrition-induced
      alterations in central serotonergic systems.

PMID- 22849970
TI  - Beneficial effect of a weight-stable, low-fat/low-saturated fat/low-glycaemic
      index diet to reduce liver fat in older subjects.
AB  - Non-alcoholic fatty liver disease is associated with insulin resistance and
      dyslipidaemia and can progress to steatohepatitis and cirrhosis. We sought to
      determine whether dietary fat and saturated fat content alter liver fat in the
      absence of weight change in an older population. Liver fat was quantified by
      magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low
      fat/low-saturated fat/low-glycaemic index (LGI) (LSAT: 23 % fat/7 % saturated
      fat/GI < 55) or a high-fat/high-saturated fat/high-GI (HSAT: 43 % fat/24 %
      saturated fat/GI>70) diet in older subjects. In the present study, twenty
      subjects (seven males/thirteen females; age 69.3 (SEM 1.6) years, BMI 26.9 (SEM
      0.8) kg/m2) were randomised to the LSAT diet and fifteen subjects (six males/nine
      females; age 68.6 (SEM 1.8) years, BMI 28.1 (SEM 0.9) kg/m2) to the HSAT diet.
      Weight remained stable. Liver fat decreased significantly on the LSAT diet
      (median 2.2 (interquartile range (IQR) 3.1) to 1.7 (IQR 1.8) %, P= 0.002) but did
      not change on the HSAT diet (median 1.2 (IQR 4.1) to 1.6 (IQR 3.9) %). The LSAT
      diet lowered fasting glucose and total cholesterol, HDL-cholesterol and LDL
      cholesterol and raised TAG (P< 0.05), while the HSAT diet had no effect on
      glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol
      (P< 0.05). Fasting insulin and homeostasis model of insulin resistance did not
      change significantly on either diet, but the Matsuda index of insulin sensitivity
      improved on the LSAT diet (P< 0.05). Assignment to the LSAT v. HSAT diet was a
      predictor of changes in lipid parameters but not liver fat. We conclude that diet
      composition may be an important factor in the accumulation of liver fat, with a
      low-fat/low-saturated fat/LGI diet being beneficial.

PMID- 22849971
TI  - Socioeconomic and geographic disparities in health information seeking and
      Internet use in Puerto Rico.
AB  - BACKGROUND: Geographically isolated Hispanic populations, such as those living in
      Puerto Rico, may face unique barriers to health information access. However,
      little is known about health information access and health information-seeking
      behaviors of this population. OBJECTIVE: To examine differences in health and
      cancer information seeking among survey respondents who ever used the Internet
      and those who did not, and to explore sociodemographic and geographic trends.
      METHODS: Data for our analyses were from a special implementation of the Health
      Information National Trends Survey conducted in Puerto Rico in 2009. We collected
      data through random digit dialing, computer-assisted telephone interviews (N =
      639). The sample was drawn from the eight geographic regions of the Puerto Rico
      Department of Health. To account for complex survey design and perform weighted
      analyses to obtain population estimates, we analyzed the data using SUDAAN.
      Frequencies, cross-tabulation with chi-square, and logistic regression analyses
      were conducted. Geographic information system maps were developed to examine
      geographic distributions of Internet use and information seeking. RESULTS: Of 639
      participants, 142 (weighted percentage 32.7%) indicated that they had ever gone
      online to access the Internet or World Wide Web; this proportion was
      substantially lower than that of US mainland Hispanics who reported using the
      Internet (49%). While 101 of 142 (weighted percentage 59.6%) respondents who used
      the Web had ever sought health information, only 118 of 497 (weighted percentage
      20.0%) of those who did not use the Web had sought health information. The
      pattern was similar for cancer information: 76 of 142 respondents (weighted
      percentage 47.2%) who used the Web had ever sought cancer information compared
      with 105 of 497 (weighted percentage 18.8%) of those who had not used the Web.
      These results were slightly lower but generally consistent with US mainland
      Hispanics' health (50.9%) and cancer (26.4%) information seeking. Results of
      separate logistic regression models controlling for sociodemographic
      characteristics demonstrated that, compared with individuals who did not seek
      health or cancer information, those who did were over 5 times as likely to have
      used the Internet (odds ratio 5.11, P < .001). Those who sought cancer
      information were over twice as likely to have used the Internet (odds ratio 2.5,
      P < .05). The frequency of Internet use and health and cancer information seeking
      was higher in the San Juan metro region than in more rural areas. CONCLUSIONS:
      Our results contribute to the evidence base for health and cancer communication
      planning for Puerto Rico, and suggest that health education and outreach efforts
      should explore the use of available and trusted methods of dissemination such as
      radio and television, as well as community-based health care providers and
      organizations, to supplement and encourage use of the Internet as a source of
      health information.

PMID- 22849972
TI  - Increased expression of transthyretin in leptin-deficient ob/ob mice is not
      causative for their major phenotypic abnormalities.
AB  - The hormone leptin is a critical regulator of adipogenesis and energy metabolism.
      Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities,
      including not only obesity and insulin resistance, but also hypogonadism and high
      bone mass. By genome-wide expression analysis using hypothalamus RNA from wild
      type and ob/ob mice, we observed the increased expression of the gene for
      transthyretin (Ttr) in the latter, as confirmed by quantitative real-time
      polymerase chain reaction. Because Ttr encodes a carrier protein for retinol
      transport, and because we further found increased retinol levels in the serum of
      ob/ob mice, we investigated whether the additional absence of Ttr would influence
      the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were
      indistinguishable from ob/ob littermates in terms of body weight, as well as
      serum glucose, insulin and cholesterol levels. Although all of these parameters
      were identical to wild-type controls in Ttr-deficient mice, we found that the
      sole deletion of Ttr caused a significant increase of trabecular bone mass, bone
      marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly,
      all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in
      these mice did we observe a full penetrance of liver steatosis at 24 weeks of
      age. Taken together, our data demonstrate that the increased expression of Ttr in
      ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.

PMID- 22849974
TI  - Feasibility of real-time magnetic resonance imaging-guided electrophysiology
      studies in humans.
AB  - AIMS: Magnetic resonance imaging (MRI) in the context of electrophysiology (EP)
      studies facilitates visualization of complex three-dimensional anatomy and the
      underlying arrhythmogenic substrate, real-time passive visualization of
      catheters, atrial and ventricular function and complications, as well as lesion
      visualization during the ablation without radiation. In the following we report
      on our first experience of a real-time MRI-guided EP study demonstrating current
      possibilities and drawbacks. METHODS AND RESULTS: Five consecutive patients (one
      male, four female; mean age 66 +/- 11 years) with symptomatic arrhythmias, three
      patients with highly symptomatic typical atrial flutter, presented to our
      hospital for isthmus ablation, one patient for an EP study and one for slow
      pathway ablation in atrioventricular node re-entry tachychardia. The four
      ablations were performed successfully in a conventional EP laboratory and
      complete bidirectional isthmus block was confirmed in three patients with atrial
      flutter. After the procedure in the EP laboratory all five patients were
      transferred to a 1.5 T whole-body MRI scanner (Intera) for a diagnostic EP
      procedure. Two MRI compatible steerable diagnostic/ablation catheters (Vision)
      were inserted via the femoral sheaths and manipulated by an experienced
      electrophysiologist using a commercially available interactive real-time steady
      state free precession sequence (repetition time = 3 ms, echo time = 1 ms, flip
      angle = 35 degrees , slice thickness = 10 mm, frame rate = 8/s). All catheters
      could be placed successfully in the right atrium and ventricle, confirmed by
      intracardiac electrograms, using passive catheter tracking. Furthermore, simple
      programmed stimulation maneuvers were performed. During and after the procedure,
      no adverse effects were observed in any patients. CONCLUSION: To our knowledge,
      this is the first series of patients with real-time MRI-guided placement of
      multiple catheters with subsequent performance of stimulation maneuvers. Besides
      the mentioned benefits, this technology still encounters several limitations,
      which have to be solved before application in a routine clinical setting.
      Challenges arise from delineation of precise surface electrocardiogram recordings
      in the MRI setting along with intracardiac electrograms, easier handling and
      visualization of catheters, facilitation of immediate defibrillation in the MRI
      setting and implementation of an active catheter tracking system.

PMID- 22849973
TI  - Non-invasive risk stratification for sudden cardiac death by heart rate
      turbulence and microvolt T-wave alternans in patients after myocardial
      infarction.
AB  - AIMS: To evaluate the predictive value of heart rate turbulence (HRT) and
      microvolt T-wave alternans (mTWA) for sudden cardiac death (SCD) in patients
      after myocardial infarction (MI). METHODS AND RESULTS: We studied 111 patients
      with MI in the previous 60 days (median, 27 [9;84] months) before inclusion (84
      men, mean age 64.1 +/- 10.5 years, mean left ventricular ejection fraction 46.6
      +/- 12.2%). Heart rate turbulence and mTWA were evaluated using 24 h ambulatory
      electrocardiogram monitoring. The primary endpoint was SCD, and the secondary
      endpoint was all-cause mortality and non-sudden death from cardiovascular causes.
      During follow-up of 12 months, 15 SCD and 8 non-sudden cardiovascular deaths
      (including five fatal MI and three fatal strokes) occurred. Non-survivors had
      significantly higher mTWA values (83 [74;165] vs. 79 [78;94] mcV, P= 0.002),
      absolute turbulence onset (TO) values (0 [-0.005;0.01] vs. -0.01 [-0.013;-0.004],
      P= 0.004), and significantly lower absolute turbulence slope (TS) values (3.34
      [2.10;4.83], vs. 3.82 [4.48;7.27], P< 0.001) compared with survivors. In patients
      with SCD, mTWA, and TO were significantly higher (92 [72;213] vs. 74 [65;86] mcV,
      P= 0.004 and 0 [-0.001;0.01] vs. -0.01 [-0.03;0.01], P= 0.007, respectively) and
      TS values were significantly lower (2.14 [1.10;4.56] vs. 4.41 [2.1;7.18], P=
      0.005) than in patients with non-sudden death. All parameters were significantly
      worse in non-survivors than in survivors. We defined cut-off values for increased
      risk of SCD: for TO = -0.005, relative risk (RR) was 12.4 [95% confidence
      interval (CI) 2.6-38.2, P< 0.001; positive predictive value (PPV) 28.3%, negative
      predictive value (NPV) 96.9%], and for mTWA > 53.5 mcV at 100 b.p.m., RR was 5.01
      (95% CI 1.5-17.0, P= 0.005; PPV 24.4%, NPV 93.9%). Notably, mTWA > 18.5 mcV at
      05.00 AM significantly increased all-cause mortality [RR 7.5 (95% CI 1.4-38.7),
      P= 0.01; PPV 19.6%, NPV 90.8%]. CONCLUSION: In patients who died from
      cardiovascular causes, mTWA, and TO values were significantly higher and TS
      values were significantly lower than in survivors, and the subgroup with SCD was
      characterized by significantly increased mTWA and TO values and decreased TS
      values. mTWA > 53.5 mcV at 100 b.p.m. was an independent significant predictor of
      SCD and increased risk of SCD by five-fold.

PMID- 22849975
TI  - Novel approach for atrial fibrillation ablation during open-heart surgery using
      cryoballoon technology.
AB  - BACKGROUND: The role of cryoballoon pulmonary vein isolation for the treatment of
      atrial fibrillation (AF) is unclear. METHODS AND RESULTS: In a 61-year-old man
      with persistent AF and severe mitral valve regurgitation, surgical cryoballoon
      pulmonary vein isolation was performed during open-heart surgery, without
      complication. CONCLUSION: Surgical cryoballoon ablation is feasible and can
      effectively isolate PV.

PMID- 22849976
TI  - Fluorescence-guided resection of gliomas.
AB  - INTRODUCTION: Malignant gliomas remain associated with a poor prognosis despite
      both surgical treatment and radiochemotherapy.Previous studies have shown that
      complete resection of contrast-enhancing tumours is achieved in less than 20-30%
      of patients. 5-aminolevulinic acid (5-ALA) is a pro-drug that leads to
      accumulation of fluorescent protoporphyrins in malignant gliomas. The
      fluorescence can be visualized intraoperatively by use of a modified microscope.
      The Department of Neurosurgery at Aalborg Hospital has recently adopted this new
      technique as the first centre in Denmark. Our preliminary results are presented
      as a retrospective case series. MATERIAL AND METHODS: All patients who had
      undergone 5-ALA fluorescence-guided surgery due to suspected malignant glioma
      were included. Patients received a standard preoperative dose of Gliolan. All
      patients had a postoperative cerebral magnetic resonance imaging scan done within
      72 hours to determine their postoperative resection status. RESULTS: To date, 13
      patients have undergone fluorescence-guided surgery. Total resection was achieved
      in 54-70% of the patients depending on the inclusion criteria. Total or near
      total resection was achieved in 92% of patients. CONCLUSION: The small numbers in
      our case series do not allow for direct comparison to be made, but show that our
      results on postoperative resection status fall within the range reported in other
      studies on the efficacy of 5-ALA. The literature offers mounting evidence in
      support of the role of aggressive cytoreductive surgery in patients with
      malignant gliomas. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22849977
TI  - Nurse administered propofol sedation for pulmonary endoscopies requires a
      specific protocol.
AB  - INTRODUCTION: This study provides an evaluation and risk analysis of propofol
      sedation for endoscopic pulmonary procedures according to our unit's
      "gastroenterologic nurse-administered propofol sedation (NAPS) guideline".
      MATERIAL AND METHODS: The present study is a prospective descriptive study
      performed at the Endoscopy Unit, Gentofte Hospital, Copenhagen, from May to July
      2009. The study comprised at total of 51 consecutive patients who underwent 77
      endoscopic procedures. Only patients above the age of 16 years were eligible for
      treatment. The exclusion criteria were as follows: American Society of
      Anesthesiologists (ASA) class > 3, history of sedation-related complications,
      severe chronic obstructive pulmonary disease. Excluded were patients with a
      potentially difficult airway and ventricular retention. Data on the number and
      type of procedure, baseline characteristics, sedation time, propofol dose
      administered and adverse events were obtained from medical histories. RESULTS: A
      total of 23 cases of adverse events were recorded, including one event of
      hypotension and 22 events of hypoxaemia. Five patients needed assisted
      ventilation. The frequency of hypoxaemia in sessions involving bronchoscopy was
      17 of 26 (65%) compared with transoesophageal endoscopic ultrasound (EUS) (17 of
      45, 35%) and endoscopic bronchial ultrasound (EBUS) (three of six, 50%).
      Endoscopist assessment of working conditions was good and patient assessment of
      discomfort was low. No patients required endotracheal intubation and there was no
      mortality. CONCLUSION: This study supports the conclusion that propofol
      administered by nurses provides for good working conditions and satisfied
      patients. But our "NAPS for endoscopic gastroenterologic procedures" guideline
      was unsuited for endoscopic pulmonary procedures including EUS. FUNDING: This
      work was supported by the START research foundation at Gentofte Hospital. TRIAL
      REGISTRATION: not relevant.

PMID- 22849978
TI  - Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major
      regional differences.
AB  - INTRODUCTION: The traditional first-line treatment for patients with advanced
      ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is
      controversial as some authors report a potential benefit from the alternative
      treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery.
      The aim of this study was to investigate the use of NACT in Denmark in regard to
      increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV
      ovarian cancer patients treated in the five Danish tertiary referral centres in
      the 2005-2010-period were included. The study is based on validated data from The
      Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients
      1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were
      treated with NACT. In 2008-2010, this percentage had risen to 30% (p < 0.00001).
      Between the five referral centres, the use of NACT ranged from 6% to 41% in 2005
      2010 (p < 0.00001); from 1 % to 31% in 2005-2007 (p < 0.00001); from 10% to 48%
      in 2008-2010 (p < 0.00001) and from 9% to 48% in 2010 (p < 0.0008). Patients
      treated with NACT were significantly older, had inferior ASA scores and Eastern
      Cooperative Oncology Group performance status compared with the patients from the
      PDS group. There was no difference between treatments in regard to body mass
      index, stage IV disease or patients with no co-morbidity. CONCLUSION: The use of
      NACT as first-line treatment tripled from 2005-2010, but the regional variability
      was large which calls for a uniform agreement on treatment principles and
      evaluation. FUNDING: This study was financially supported by grants from The
      Copenhagen University Hospital Research Foundation, Manufacturer Einar Willumsens
      Memorial Trust, The Capital Region of Denmark Research Foundation, The Arvid
      Nilsson Foundation, The King Christian X Foundation, The Dagmar Marshall
      Foundation, The Danish Research Foundation, and The Hans and Nora Buchard
      Foundation. TRIAL REGISTRATION: not relevant.

PMID- 22849979
TI  - Same review quality in open versus blinded peer review in "Ugeskrift for Laeger".
AB  - INTRODUCTION: Research into the peer review process has previously been conducted
      in English-language journals. This study deals with a Danish general medical
      journal with a relatively small pool of both reviewers and readers. The aim of
      the study was to compare the quality of reviews produced by identifiable and
      anonymous reviewers, and further to characterize authors' and reviewers'
      attitudes towards different peer review systems. MATERIAL AND METHODS: The study
      was conducted as a blinded, randomised controlled trial. Each manuscript was
      reviewed by an identifiable and an anonymous reviewer. Review quality was
      subsequently assessed by two blinded editors, using the validated Review Quality
      Instrument. Reviewers' and authors' attitudes towards different peer review
      systems were characterized using questionnaires. RESULTS: The study included 364
      reviews. There was no statistically significant difference in quality between
      anonymous and identifiable reviewers' evaluations. 55% of the authors preferred
      the evaluation produced by the identifiable reviewer (p < 0.05). 26% of the
      identifiable reviewers found it unpleasant that authors knew their identities;
      43% of the anonymous reviewers found it reassuring that authors did not know
      their identities. Regarding reviewers' preferences for different peer review
      systems, 38% preferred a double-blinded, 34% preferred a single-blinded and 28%
      preferred an open system. For authors, the corresponding proportions were 43%,
      19% and 37%. CONCLUSION: Implementing open peer review will not affect review
      quality, but lack of anonymity may cause reviewers, already limited in number, to
      decline when asked to review. Even though this would be a serious implication for
      a national journal like the Ugeskrift for Laeger, the implementation of an open
      system should be discussed. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22849980
TI  - Inadequate follow-up after tracheostomy and intensive care.
AB  - INTRODUCTION: When patients are transferred from intensive care units (ICUs) to
      general wards with a tracheostomy in situ, there is a risk of suboptimal care and
      increased morbidity. The aim of this study was to elucidate the management of
      patients with a tracheostomy in situ at discharge from the ICU to the ward.
      MATERIAL AND METHODS: We performed an electronic questionnaire survey among heads
      of unit at registered Danish ICUs. RESULTS: A total of 34 out of 43 ICUs
      responded. 56% of the ICUs do not document individual plans for decannulation in
      the patient's chart. 91% of the ICUs do not perform daily follow-up of
      tracheotomised patients on the ward. No guidelines for decannulation on the ward
      were found, and only 6% have a guideline for accidental decannulation.
      Furthermore, as little as 47% of the ICUs report any formalized education or
      training of staff nurses in the management of tracheotomised patients.
      CONCLUSION: Guidelines relevant to patients discharged from Danish ICUs with a
      tracheal cannula in situ are scarce; few ICUs employ individualized plans for
      tracheostomy management and decannulation; there is largely no daily intensivist
      led post-ICU follow-up, and formal staff education in tracheostomy management on
      the ward is scarce. Altogether these factors create a potential for adverse
      events and increased morbidity in this high-risk, high-cost patient population.
      Possibly individualized plans for tracheotomised patients as well as intensivist
      led follow-up on the ward can improve patient outcome and safety and this should
      be confirmed in a future study. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22849981
TI  - Telephone hotline is an important part of overall patient management in upper
      gastrointestinal malignancies.
AB  - INTRODUCTION: As seven out of every ten patients with upper gastrointestinal
      malignancies (UGIM) are not eligible for curative treatment, life after diagnosis
      is characterised by a rapid deterioration and uncertainty. To accommodate these
      issues, we established a telephone hotline. MATERIAL AND METHODS: In a two-year
      period, all patients evaluated for UGIM were given the hotline phone number. The
      hotline was staffed by either a nurse or a secretary, and subsequently the
      specialist in charge of the patient would return the call. All calls were
      registered in a prospective database. The following data were recorded:
      diagnosis, time from call to return call, problem and solution to the problem.
      RESULTS: A total of 477 patients were included, and 172 (36%) patients used the
      Hotline a total of 254 times. Of the 254 calls, 210 (83%) were returned the same
      day. A total of 104 (41%) calls were made due to elaborative questions and 89% of
      these were solved over the phone. Dysphagia was the problem in 51 cases which
      gave rise to an endoscopy in 86% of cases. Pain was the problem in 35. Overall,
      of the 254 calls, 152 (60%) problems were solved over the phone. Furthermore, 75
      calls triggered a hospital visit and 27 calls led to the patient being referred
      for further examinations. CONCLUSION: The establishment of a telephone hotline
      was feasible and it was used by some patients. Most of the callers only made one
      call. Nearly all calls (96%) were returned the day after the initial call, at the
      latest. The problem pattern did not differ between disease groups apart from
      dysphagia in oesophageal cancer. We found that the hotline was an effective and
      inexpensive part of overall patient management. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 22849982
TI  - Individual and environmental risk factors for high blood lead concentrations in
      Danish indoor shooters.
AB  - INTRODUCTION: International studies have shown blood lead at levels causing
      health concern in recreational indoor shooters. We hypothesized that Danish
      recreational indoor shooters would also have a high level of blood lead, and that
      this could be explained by shooting characteristics and the physical environment
      at the shooting range. MATERIAL AND METHODS: This was an environmental case study
      of 58 male and female shooters from two indoor shooting ranges with assumed
      different ventilation and cleaning conditions. Information was obtained on
      general conditions including age, gender, tobacco and alcohol use, and shooting
      conditions: weapon type, number of shots fired, frequency of stays at the
      shooting range and hygiene habits. A venous blood sample was drawn to determine
      blood lead concentrations; 14 non-shooters were included as controls. RESULTS:
      Almost 60% of the shooters, hereof five out of 14 women, had a blood lead
      concentration above 0.48 micromol/l, a level causing long-term health concern.
      All controls had blood lead values below 0.17 micromol/l. Independent significant
      associations with blood lead concentrations above 0.48 micromol/l were found for
      shooting at a poorly ventilated range, use of heavy calibre weapons, number of
      shots and frequency of stays at the shooting range. CONCLUSION: A large
      proportion of Danish recreational indoor shooters had potentially harmful blood
      lead concentrations. Ventilation, amounts of shooting, use of heavy calibre
      weapons and stays at the shooting ranges were independently associated with
      increased blood lead. FUNDING: The technical check at the two ranges was
      performed by the Danish Technological Institute and costs were defrayed by the
      Danish Rifle Association. To pay for the analyses of blood lead, the study was
      supported by the The Else & Mogens Wedell-Wedellsborg Foundation. TRIAL
      REGISTRATION: The Danish Regional Capital Scientific Ethics Committee approved
      the study, protocol number  H-4-2010-130.

PMID- 22849983
TI  - Opinions among Danish knee surgeons about indications to perform total knee
      replacement showed considerable variation.
AB  - INTRODUCTION: During the past decade, the incidence of primary total knee
      replacement (TKA) surgery in Denmark has approximately doubled. This increase
      could be due to weakened indications to perform TKA surgery. We aimed to
      investigate variation in opinions about indications to perform TKA among Danish
      knee surgeons. MATERIAL AND METHODS: In October 2011, a survey among Danish knee
      surgeons was performed at the Annual Meeting of the Danish Orthopaedic Society. A
      questionnaire targeting knee surgeons' opinion on indications for primary TKA was
      distributed. Questions concerned opinions on aspects of pain, body mass index
      (BMI), exercise, function, age, clinical and radiographic findings, and specific
      patient cases. RESULTS: A total of 41 questionnaires were returned. Twenty-three
      knee surgeons performed > 100 TKAs annually. Opinions about the duration of knee
      pain and pain treatment, preoperative weight loss and exercise, excessive BMI as
      a contraindication, low age as a contraindication, and some of the specific
      patient cases demonstrated considerable variation. A statistically significantly
      higher proportion of high-volume versus low-volume knee surgeons did not find
      that BMI could be a contraindication to proceed with TKA surgery (p = 0.02).
      CONCLUSION: Opinions among knee surgeons about indications to perform TKA showed
      considerable variation. The majority of the variation observed is tolerable and
      may be explained by lack of evidence or diverging literature reports. However,
      variation in opinions regarding preoperative weight loss and exercise may warrant
      the introduction of further guidelines for involved care takers. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 22849984
TI  - Indications for knee arthroplasty have remained consistent over time.
AB  - INTRODUCTION: Between 2004 and 2009, the incidence of primary total knee
      arthroplasty (TKA) in Denmark has almost doubled. It has been speculated that
      this increase may be a result of patients being operated on weaker indications.
      The purpose of this study was to compare preoperative degrees of osteoarthritis
      and health-related quality of life (QoL) in patients receiving primary TKA in
      2004 and 2009. MATERIAL AND METHODS: We identified 154 and 369 primary TKAs
      inserted at our institution in 2004 and 2009, respectively. Patients had been
      invited to complete the Short Form (SF)-36 questionnaire preoperatively. Two
      groups of patients that were representative with regard to age and gender were
      randomly sampled and compared (n = 44 in 2004 versus n = 106 in 2009). The
      Kellgren-Lawrence (K-L) grade of osteoarthritis was assessed on preoperative
      radiographs in all patients. RESULTS: We found no statistically significant
      differences in gender distribution or mean age at surgery. We reached K-L grades
      of 3-4 in 52.4% and 49.6% in 2004 and 2009, respectively (p = 0.57). The
      preoperative mean SF-36 physical component scores were 32.6 and 33.7,
      respectively (p = 0.44). The preoperative mean SF-36 mental component scores were
      43.0 in 2004 and 49.3 (i.e. 6.3 points higher) in 2009 (p = 0.003). CONCLUSION:
      Preoperative degrees of osteoarthritis and physical health-related QoL did not
      change from 2004 to 2009. Thus, it seems that these components of operative
      indications have not weakened. The increased preoperative SF-36 mental component
      score of these patients may have had a positive effect on postoperative outcomes.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22849985
TI  - Organ dysfunction following regional and global ischemia/reperfusion.
      Intervention with postconditioning and adenocaine.
AB  - Cardiac arrest and acute myocardial infarction are leading causes of death in the
      middle-aged and elderly, whereas trauma primarily affects the younger segment of
      the population. The three conditions are all characterized by a period of reduced
      blood flow either regionally in the heart or globally, and treatment strategies
      target the restoration of normal blood flow. Paradoxically, reperfusion of
      ischemic tissue contributes to cellular injury in all three settings. Ischemic
      postconditioning initiated immediately at reperfusion was in 2003 introduced as a
      new potential treatment to limit injury following acute myocardial infarction.
      The aim of this dissertation was explore the mechanism of ischemic
      postconditioning during regional ischemia and test the effects of early
      pharmacological postconditioning using adenocaine in models of global I/R injury.
      In the first study, the mechanisms of postconditioning were explored. In a rat
      model of regional ischemia, it was demonstrated that postconditioning reduced
      infarct size. However when postconditioning was applied in already PMN-depleted
      rats, no further reduction in infarct size was observed. Furthermore, in a canine
      model of regional ischemia, postconditioning attenuated PMN superoxide
      production, implying that cardioprotection by postconditioning involves
      inhibition of PMNs. In the second study, treatment with adenocaine as
      pharmacological postconditioning during the immediate phase of cardiopulmonary
      resuscitation, attenuated early post-resuscitation myocardial dysfunction,
      augmented pulmonary and cardiac blood flow and reduced PMN superoxide production
      in a porcine model of cardiac arrest. In the third study, treatment with ALM/AL
      during the early phase of resuscitation was tested in a porcine model of
      hemorrhagic shock. Resuscitation with ALM/AL reduced fluid requirements during
      fluid resuscitation, transiently reduced whole body O2 consumption and improved
      cardiac and renal function. In conclusion, early intervention with either
      postconditioning or adenocaine attenuates I/R injury and organ dysfunction in
      animal models of acute myocardial infarction, cardiac arrest or hemorrhagic
      shock. Postconditioning and adenocaine may be promising new therapies for
      protection against I/R after acute myocardial infarction, cardiac arrest and
      hemorrhagic shock.

PMID- 22849986
TI  - Drug utilization and asthma control among young Danish adults with asthma.
      Analyses of trends and determinants.
AB  - This PhD thesis was performed during my employment at the Research Unit of
      General Practice in Odense, University of Southern Denmark. It comprises an
      overview of three papers, all published or submitted for publication in
      international peer-reviewed scientific journals. BACKGROUND: Observational
      studies have revealed inadequate use of inhaled corticosteroids (ICS) among
      asthmatics. However, only limited data exist on whether ICS usage has changed
      over time. In addition, improved knowledge is needed on factors associated with
      ICS use and asthma control in order to identify subjects at risk of being
      inadequately treated. AIMS: Among young adult Danish asthmatics we aimed:  To
      investigate trends in ICS use and factors associated with ICS use during 1997
      2006 (Study I).  To investigate associations between socioeconomic status
      (education and income) and ICS use, and whether these associations were
      consistent over time during 1997-2005 (Study II).  To investigate whether
      particular prescribing patterns of anti-asthmatic drugs were associated with
      clinically uncontrolled asthma (Study III). METHODS: Three studies were carried
      out among Danish users of anti-asthmatic drugs aged 18-44 years. Study I (N = 106
      757) and Study II (N = 97 665) were longitudinal studies based on repeated annual
      cross-sectional analyses on national register data. Study III (N = 357) was a
      cross-sectional study based on register and clinical data from a municipal cohort
      from Odense, Denmark. RESULTS: Study I: We observed an annual increase in one
      year prevalence of ICS use from 67% in 2001 to 77% in 2006, occurring
      concurrently with the introduction of fixed dose combination therapy with ICS and
      inhaled long-acting beta-2-agonists. Still some 20-30% of subjects with a massive
      annual IBA consumption were not prescribed ICS. Factors associated with ICS use
      were high annual use of inhaled beta-2-agonists (IBA), female gender, age 18-24
      years, use of leukotriene receptor antagonists, and use of drugs for rhinitis and
      specific immune therapy. Study II: High levels of education (OR 1.46, 95% CI 1.40
      1.51) and income (OR 1.10, 95% CI 1.06-1.14) were found to be positively
      associated with ICS use with the most pronounced impact among 35-44 year-olds.
      Higher education showed an almost constant association with ICS use each year
      throughout the entire observation period, but high income did not demonstrate any
      statistically significant association with ICS use before 2001 (OR 1.10, 95% CI
      1.02-1.18) with increasing ORs observed each year hereafter (OR 1.30, 95% CI 1.20
      1.40 in 2005). Study III: A total of 96 of the clinically assessed subjects
      (26.9%) had uncontrolled asthma. An increasing association between uncontrolled
      asthma and an increasing annual quantity of inhaled short-acting beta-2-agonists
      (SABA) usage was demonstrated. Due to a substantial overlap in levels of SABA use
      among controlled and uncontrolled asthmatics this association was not strong
      enough to allow conclusions on individual asthma patients. CONCLUSION: The
      results support previous findings by demonstrating a continuing inadequate use of
      ICS among young adult asthmatics with a consistent and high use of reliever
      therapy, which was associated with uncontrolled asthma. This apparent over
      reliance on reliever therapy and possible non-adherence to ICS may indicate
      inefficient guideline implementation among patients and physicians, leaving room
      for further improvement. The clear indications of a socioeconomic gradient in ICS
      use further emphasizes that knowledge of patient-related factors associated with
      asthma treatment and asthma control is imperative for health care professionals
      to be able to identify subjects deserving special attention.

PMID- 22849987
TI  - Barrett's esophagus. Diagnosis, follow-up and treatment.
AB  - Barrett's Esophagus (BE) is a premalignant condition in the esophagus. Esophageal
      adenocarcinomas have the fastest increase of incidence of all solid tumors in the
      western world. BE is defined as areas with macroscopic visible columnar
      epithelium and intestinal metaplasia oral of the anatomical gastroesophageal
      junction. The extent of the endoscopic findings is described by the Prague
      classification. The metaplasia is histologically confirmed by the presence of
      intestinal metaplasia. The diagnosis of BE can only be made by a combined
      macroscopic and microscopic examination. The histological description should
      include evaluation of dysplasia, and if present it should be classified as low or
      high grade dysplasia. All patients are offered relevant antireflux treatment with
      PPI or surgery. Ablation or mucosal resection of metaplastic epithelia with or
      without low grade dysplasia is experimental and it is not recommended outside
      controlled studies. Treatment of high grade dysplasia and carcinoma in situ is
      handled in departments treating esophageal cancer. Follow-up with endoscopy and
      biopsy can be offered. Follow-up endoscopy with biopsy can only be recommended
      after thorough information to the patients, as evidence for the value is scarce.

PMID- 22849988
TI  - [Diagnosis and management of cervical spondylosis].
AB  - Cervical spondylosis, which can present as radiculopathy and myelopathy, is
      common in people over the age of 50. Since evidence of radiological spondylotic
      change is frequently found in many asymptomatic adults, it is necessary to assess
      whether neurological symptoms result from cervical spondylosis or other
      neurological disorders. In order to avoid misdiagnosis, it is important to
      compare the levels of the lesions shown on imaging with the clinical findings.
      Differential diagnosis between amyotrophic lateral sclerosis and cervical
      spondylotic myelopathy is an issue of major clinical importance. Though the
      course of disease development and the ultimate prognosis for patients with
      cervical spondylosis is highly variable and extremely difficult to predict, many
      patients experience a relatively benign form of the disease.

PMID- 22849989
TI  - [An autopsy case of pandemic (H1N1) 2009 influenza virus-associated
      encephalopathy].
AB  - A 16-year-old male was admitted to our hospital because of fever, altered
      consciousness and subsequent tonic convulsions of upper and lower extremities. A
      head CT scan revealed evidence of diffuse brain edema. Novel influenza H1N1 viral
      RNA was detected in nasopharyngeal specimens by specific PCR examination.
      Oseltamivir, steroid pulse and intravenous immunoglobulin were administered
      without any effect. On day 3 after admission, the patient died of complications
      of DIC and multiple organ failure. Autopsy revealed neuropathological changes of
      the central nervous system, including congestion and marked edema of the brain.
      However, inflammatory cell infiltration in the meninges or brain parenchyma was
      not observed. Extensive disruption of astrocytic projections (clasmatodendrosis),
      which is indicative of acute encephalopathy, was detected by anti-glial
      fibrillary acidic protein (GFAP) immunostaining of brain tissue. This is the
      first autopsy case report of pandemic (H1N1) 2009 influenza virus-associated
      encephalopathy. The clinical course, laboratory profiles and pathological
      findings were similar to those of conventional seasonal influenza encephalopathy
      in children that are reported previously.

PMID- 22849990
TI  - [Remission of lymphomatosis cerebri induced by corticosteroid and high-doses
      intravenous methotrexate].
AB  - Lymphomatosis cerebri (LC) is a rare form of primary central nervous system
      lymphoma characterized by subacute progressive dementia and unsteady gait. MRI
      study of LC typically reveals diffuse leukoencephalopathy without contrast
      enhancement. The clinical presentation and MRI features of LC can resemble
      infectious, inflammatory, toxic or vascular leukoencephalopathy. Hence diagnosis
      of LC is easily mistaken for other, more common diseases. In this report, we
      present a case of a 55-year-old man presenting with subacute progressive dementia
      and ataxic gait. Brain MRI showed diffuse hyperintense lesions in the cerebral
      white matter of both hemispheres, left amygdala, brainstem and cerebellar
      peduncles on FLAIR image. No contrast-enhanced lesion was observed. Cerebrospinal
      fluid analysis showed elevated levels of soluble interleukin-2 receptor and beta2
      microglobulin. Based on MRI findings and 123I-IMP SPECT, stereotactic biopsy
      targeting white matter of the left medial temporal lobe was performed (day 0). On
      the day after the brain biopsy, corticosteroid therapy was initiated and improved
      the patient's cognitive function and gait disturbance. Pathological diagnosis of
      large B-cell lymphoma was obtained on day 9. High-dose intravenous methotrexate
      chemotherapy was started on day 14 and led to complete remission by day 52. This
      case highlighted the importance of brain biopsy for diagnosis of LC. This report
      raises a possibility that timely and proper treatment leads to a favorable
      outcome of LC that has been regarded as an intractable disease with poor
      prognosis.

PMID- 22849991
TI  - [A case of Sjogren syndrome with subacute combined degeneration-like posterior
      column lesion on cervical MRI].
AB  - We report a case of a 67 year-old man with bilateral sensory ataxia of the upper
      extremities. He was diagnosed as having ANCA-related angitis and Sjogren syndrome
      at age 60. On admission to our hospital at age 67, he presented with severe
      sensory ataxia in his upper extremities, while his lower extremity neurological
      symptoms were limited to the absence of tendon reflexes. Cervical MRI showed an
      increased T2 signal intensity in an area limited to the bilateral cuneate
      fasciculus. Serum levels of vitamin B12 and folic acid were normal. Plasma
      homocysteine, serum and urine methylmalonic acid were also normal. Eight-week
      intramuscular administration of vitamin B12 did not improve either his disorder
      or the MRI findings. His sensory ataxia might be attributed to Sjogren syndrome
      associated ganglionopathy at the cervical level, and the MRI findings might
      reflect centripetal Wallerian degeneration in the cuneate fasciculus. Gracilis
      fasciculus are well-known as vulnerable regions in Sjogren-associated myelopathy,
      whereas cervical myelopathy, limited to cuneate fascicules, can emerge as Sjogren
      associated disorders.

PMID- 22849992
TI  - [A case of dysferlinopathy asymptomatic for 10 years after an episode of
      transient muscle weakness].
AB  - We report a 28-year-old male with dysferlinopathy, who has remained asymptomatic
      for 10 years from a rhabdomyolysis-like episode. He had been in good health since
      birth, but felt difficulty in walking after a month and a half of manual labor at
      18 years old (at the year 2000). Rhabdomyolysis was suspected because of muscle
      weakness and elevated serum CK of 28,094U/L. He was hospitalized and his muscle
      weakness improved. He was referred to us, because his serum CK remained around
      2,000U/L. Histological analysis of muscle, when anti-dysferlin antibody was
      unavailable, was not informative but later analysis at the age of 23 using
      preserved specimen showed loss of dysferlin immunoreactivity. Subsequently, a
      missense mutation (c.2997G>T) and a deletion (c.3373delG) of the dysferlin gene,
      both of which are common in Miyoshi myopathy in Japanese, were identified. He
      continuously showed hyper-CKemia, but no apparent muscle weakness emerged for
      more than ten years. Reports on asymptomatic dysferlinopathy over such a long
      duration are rare. This case may suggest that genetic factors, environmental
      factors such as intensity of work-load, or both, might affect the clinical course
      of dysferlinopathy. Further follow-up is necessary.

PMID- 22849993
TI  - [Migraine with aura and recurrent vertigo attacks in a patient with hereditary
      hemorrhagic telangiectasia].
AB  - Hereditary hemorrhagic telangiectasia (HHT) is characterized by systemic vascular
      diseases mainly shown as arterio-visnous fistula (AVF). Here, we presented a 29
      year-old woman with HHT complicated with migraine with aura (MWA) and vertigo. At
      the age of twelve years, she developed migraine with visual aura. At that time,
      migraine attacks were seen three times a year. At the age of 29 years, she also
      developed speech disturbance as migraine aura. At the ages of 20 and 29 years,
      she repeatedly suffered from positional vertigo attacks for a month. Physical
      examination revealed dilation of the capillary vessels at tongue, soft palate,
      and nasal mucosa and AVFs were located in the upper cervical cord, parietal lobe,
      and bilateral lungs. These clinical findings were consistent with the diagnostic
      criteria of HHT. Embolization of pulmonary AVF decreased the frequency of
      migraine attacks during 2-year follow-up after the embolization. The frequency of
      migraine in patients with HHT is higher than that of general population as well
      as the prevalence of vertigo. Therefore, MWA and vertigo presented in the patient
      with HHT suggests that there is a common pathological mechanism of dysfunction of
      endothelial cells and R-L shunt, among HHT, MWA, and vertigo.

PMID- 22849994
TI  - [Myasthenia gravis complicated with optic neuritis showing anti-aquaporin 4
      antibody: a case report].
AB  - We report a 33-year-old woman with myasthenia gravis (MG) who developed optic
      neuritis after the treatment of MG for 22 years. At 10 years of age, she was
      diagnosed with generalized MG (MGFA V) and at 11 years, she underwent thymectomy.
      She had been treated successfully only with anti-cholinesterase inhibitors for 22
      years despite lasting high titer of anti-acetylcholine receptor antibody. She
      could manage everything in her life and had two children. At 33 years of age, she
      experienced acute visual loss in her left eye. Laboratory examination showed
      positive anti-acetylcholine receptor, antinuclear, anti-ssDNA, anti-dsDNA, anti
      SS-A, and anti-aquaporin 4 (AQP4) antibodies. Brain MRI showed an enlarged left
      optic nerve with enhancement by gadolinium. Three courses of steroid pulse
      therapy did not show any effect on her visual acuity. However, plasma exchange
      therapy mildly ameliorated her visual acuity. Her MG symptoms were not
      exacerbated during the course of the optic neuritis. Furthermore blephalopstosis
      caused by MG has disappeared completely after the treatment with steroid pulse
      and plasma exchange. This case had 23 years of immunosuppressive treatment free
      durations with stable condition. The cause of development of optic neuritis would
      be her predisposed tendency other than thymectomy or treatment with
      immunosuppressive therapies.

PMID- 22849995
TI  - [A case of Churg-Strauss syndrome presenting with lower cranial neuropathy].
AB  - We reported a 60 year-old man with Churg-Strauss syndrome (CSS). Three months
      later, he presented with dysarthria, dysphagia and severe headache. We detected
      glossopharyngeal and vagal nerve palsy, and made a diagnosis of cranial nerve
      involvement comorbid with CSS. Intravenous administration of methypredonisolone
      was effective for alleviating clinical signs and symptoms. Two months later, he
      complained of headache and facial numbness, but symptoms improved with an
      escalating dose of prednisolon. As compared to previously reported cases, our
      case was characteristic because of involvement of lower cranial nerve with CSS,
      which has been reported previously in only one case.

PMID- 22849996
TI  - [Osmotic substances might be harmful in cerebral venous thrombosis].

PMID- 22850020
TI  - Translating exome sequencing from research to clinical diagnostics.
AB  - In the relatively short time frame since the introduction of next generation
      sequencing, it has become a method of choice for complex genomic research
      studies. As a paradigm shifting technology, we are now witnessing its translation
      into clinical diagnostic laboratories for patient care. Multi-gene panels for a
      variety of disorders are now available in several clinical laboratories based on
      targeted gene enrichment followed by next generation sequencing. Genome wide
      interrogation of protein coding regions, or exome sequencing, has been
      successfully and increasingly applied in the research setting for the elucidation
      of candidate genes and causal variants in individuals and families with a
      diversity of rare and complex genetic disorders. Based on this progress, exome
      sequencing is also beginning a translational process into clinical practice.
      However, introducing exome sequencing as a diagnostic modality poses new
      technical and bioinformatics challenges for clinical laboratories. In this
      review, we present technical and bioinformatics aspects of exome sequencing,
      describe representative examples from the literature of how exome sequencing has
      been used for candidate gene discovery, and discuss considerations for its
      clinical translation.

PMID- 22850049
TI  - Quality assurance and quality control in the routine molecular diagnostic
      laboratory for infectious diseases.
AB  - Molecular diagnostics has become one of the dominant platforms in clinical
      laboratory medicine. Technological improvements, from automated sample
      preparation to real time amplification technology, provide the possibility to
      develop and run assays for a growing number of clinical questions. However,
      quality assurance and quality control issues have often remained underdeveloped
      but are still critical. To relate patient results to prior results or to absolute
      values in clinical practice guidelines, those results need to be comparable
      across time and methods. This may be achieved either by producing the identical
      value across methods and test versions or by using reliable and stable
      conversions. The establishment of international standards and reference materials
      is thus of paramount importance. This review focuses on general and specific
      issues relevant for quality assurance and quality control in the routine
      molecular diagnostics laboratory.

PMID- 22850050
TI  - Laboratory approaches for predicting and managing the risk of cardiovascular
      disease: postanalytical opportunities of lipid and lipoprotein testing.
AB  - Abstract Lipoprotein-related risk of cardiovascular disease (CVD) can be
      adequately predicted in subjects with elevated total cholesterol and low-density
      lipoprotein (LDL-)cholesterol using the available guidelines. However,
      individuals with dyslipidemia can have normal total- and LDL-cholesterol
      concentrations. Many statin-treated patients remain at high residual risk of CVD
      despite achieving LDL goals. The small dense LDL phenotype, frequently presenting
      with hypertriglyceridemia and low high-density lipoprotein (HDL-)cholesterol
      (lipid triad), may contribute to failure to identify and treat high-risk
      individuals. Therefore, calculated non-HDL-cholesterol is recommended as
      secondary therapeutic target to LDL-cholesterol in patients with
      hypertriglyceridemia and mixed dyslipidemia. On-treatment apolipoprotein B adds
      prognostic information to LDL- and non-HDL-cholesterol by indicating the total
      number of atherogenic lipoproteins, regardless of their cholesterol content. Risk
      may be higher than indicated in the risk estimation systems in additional
      subjects with elevated lipoprotein(a) and homocysteine concentrations. To improve
      the (post-)post-analytical phase of lipid tests, aiming for maximal health
      outcome effectiveness of test interpretation and utilization, laboratory
      professionals should deliver clinical added value services by providing readily
      interpreted and guideline-adjusted test reports, interpretative commenting,
      proactive reflex testing or recommending additional tests, and joining
      multidisciplinary cooperations in guideline development and cost/benefit studies.

PMID- 22850051
TI  - Pregnancy-associated plasma protein A: spotlight on kidney diseases.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is a biomarker routinely used in
      screening for Down syndrome in the first trimester of pregnancy. It is also
      present in very small amounts in men and non-pregnant women. PAPP-A is a key
      regulator of local insulin-like growth factor (IGF) bioavailability - IGFs are
      essential for normal body size during fetal development, but they are associated
      with aging and age-related diseases. Measurement of circulating PAPP-A can
      provide valuable information not only in pregnant women (chromosomal anomalies
      and adverse pregnancy outcomes) but also in patients with coronary artery disease
      (contribution to diagnosis, prognostic value) and in patients with kidney
      diseases. PAPP-A is associated with renal function and proteinuria, is increased
      mainly in dialysis patients and decreases after kidney transplantation. It is an
      independent mortality predictor of hemodialysis patients and indicator of adverse
      outcome of transplanted patients. PAPP-A levels can be influenced by various
      chemicals and drugs, among them mainly heparin. Various assays for PAPP-A exist
      and the type of assay used in a study should be considered. This article reviews
      the data summarizing basic information about PAPP-A with a particular focus on
      the significance of PAPP-A in renal diseases.

PMID- 22850052
TI  - Measurement of factor XIII activity in plasma.
AB  - Coagulation factor XIII (FXIII) is converted by thrombin and Ca(2+) into an
      active transglutaminase (FXIIIa) in the final phase of coagulation cascade. Its
      main function is the mechanical stabilization of fibrin clot and its protection
      from fibrinolysis by cross-linking of fibrin chains and alpha(2)-plasmin
      inhibitor to fibrin. In non-substituted patients FXIII deficiency is a severe
      hemorrhagic diathesis, not infrequently with fatal consequences. The main reason
      for using FXIII assays is the diagnosis of FXIII deficiency. The aim of this
      review is to provide a comprehensive critical evaluation of the methods reported
      for the determination of FXIII activity in the plasma. Such methods are based on
      two principles: 1) measurement of labeled amines incorporated by FXIIIa into a
      glutamine residue of a substrate protein, 2) monitoring ammonia released from a
      peptide bound glutamine residue by FXIIIa using NAD(P)H dependent glutamate
      dehydrogenase indicator reaction. The incorporation assays are sensitive, but
      cumbersome and time-consuming, they are difficult to standardize and cannot be
      automated. The ammonia release assays are less sensitive, but quick, well
      standardized, and can be automated; this type of assay is recommended for the
      screening of FXIII deficiency. The traditional clot solubility assay should not
      be used for this purpose.

PMID- 22850053
TI  - Update on multiple sclerosis, its diagnosis and treatments.
AB  - Multiple sclerosis (MS) is a central nervous system disorder, characterized by
      mononuclear cell inflammation, demyelination and often with extensive axonal
      injury. It was first described neuropathologically in the late 1800s. MS has an
      interesting geographical epidemiology, with a higher rate at latitudes further
      from the equator in both directions. Women outnumber males by about 2:1; this
      ratio has been increasing in recent years. Genome wide association studies have
      thus far identified over 50 genetic susceptibility loci, and these are rapidly
      expanding. Several environmental risk factors have been identified, including low
      serum vitamin D levels, exposure to Epstein-Barr virus and cigarette smoking. MS
      displays a heterogeneous disease course; most patients with the disease begin
      with a relapsing-remitting course, but often eventually develop steady disability
      progression. A small percentage of MS patients have a progressive course without
      clinical relapses. Several treatments are now available to decrease relapse rate
      and slow the accumulation of disability in patients with relapsing MS, but there
      is currently no effective treatment to slow the progressive forms of MS.

PMID- 22850054
TI  - Recommendations on prenatal screening and the connections to other diseases such
      as thyroid dysfunction.
AB  - The aim of general maternal-foetal care is to ensure an uncomplicated birth of a
      healthy baby to a healthy mother. There is a large range of screening tests used
      during pregnancy: for gestational diabetes, infection, rhesus-D status, thyroid
      dysfunction, as well as other tests. An important part of prenatal care is the
      screening of major aneuploidies, primarily for Down's syndrome. This screening is
      possible in either the first or second trimester, or in both. Management of this
      type of screening is very similar around the world. Hypothyroidism can affect the
      psychomotor development of the child. Thyroid-stimulating hormone (TSH),
      autoantibodies against thyroperoxidase (TPOAb), and free thyroxin (FT4) were
      determined within our group of 7530 pregnant women. Elevated concentrations of
      TSH were found in 5.1%, suppression was found in 2.9% and 11.5% were TPOAb
      positive. Either a familial or personal history of thyroid or autoimmune diseases
      was present in 58.3% of those women who tested positive on any thyroid test. At
      minimum, 40% of women TPOAb positive during pregnancy have some kind of thyroid
      disorders after delivery. These results support the efficacy of general thyroid
      function screening in early pregnancy, as well as the follow-up after delivery of
      those women who are positive.

PMID- 22850055
TI  - Implementation of standardization in clinical practice: not always an easy task.
AB  - As soon as a new reference measurement system is adopted, clinical validation of
      correctly calibrated commercial methods should take place. Tracing back the
      calibration of routine assays to a reference system can actually modify the
      relation of analyte results to existing reference intervals and decision limits
      and this may invalidate some of the clinical decision-making criteria currently
      used. To maintain the accumulated clinical experience, the quantitative
      relationship to the previous calibration system should be established and, if
      necessary, the clinical decision-making criteria should be adjusted accordingly.
      The implementation of standardization should take place in a concerted action of
      laboratorians, manufacturers, external quality assessment scheme organizers and
      clinicians. Dedicated meetings with manufacturers should be organized to discuss
      the process of assay recalibration and studies should be performed to obtain
      convincing evidence that the standardization works, improving result
      comparability. Another important issue relates to the surveillance of the
      performance of standardized assays through the organization of appropriate
      analytical internal and external quality controls. Last but not least,
      uncertainty of measurement that fits for this purpose must be defined across the
      entire traceability chain, starting with the available reference materials,
      extending through the manufacturers and their processes for assignment of
      calibrator values and ultimately to the final result reported to clinicians by
      laboratories.

PMID- 22850056
TI  - IFCC standardised HbA(1c): should the world be as one?
AB  - The central importance of HbA(1c) in monitoring glycaemic control was highlighted
      by the Diabetes Control and Complications Trial (DCCT) which showed that improved
      glycaemic control, as monitored by HbA(1c), delayed the onset of diabetic
      complications. Following this publication the issue of international
      standardisation of glycated haemoglobin (GHb) measurements became an important
      objective. The lack of international standardisation resulted in several
      countries developing National Standardisation Programmes. The International
      Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on
      HbA(1c) Standardisation has established a reference measurement procedure (HPLC
      MS or HPLC-CE) for HbA(1c) embracing the concept of metrological traceability.
      The reference method is anchored to a global network of 15 approved reference
      laboratories; this confers sustainability and a low level of uncertainty.
      Essential elements of a comprehensive reference measurement system additionally
      include the definition of the measurand and the unit of measurement. HbA(1c) is
      defined as haemoglobin (Hb) molecules having a stable adduct of glucose to the N
      terminal valine of the beta chain [Hb beta chain (Blood) - N-(1-deoxyfructos-1
      yl) Hb beta chain] and that mmol/mol be used as the unit of measurement. These
      developments will result in improvements in inter-method and inter-laboratory
      agreement. Additionally, global acceptance of standardisation based on
      metrologically sound principles will enable clinical goals and diagnostic
      guidelines to be developed that can be adopted by all countries.

PMID- 22850057
TI  - Reflective testing: adding value to laboratory testing.
AB  - Reflective testing is a procedure in which the laboratory specialist adds
      additional tests and/or comments to an original request, after inspection
      (reflection) of the results. It can be considered as an extension of the
      authorization process where laboratory tests are inspected before reporting to
      the physician. The laboratory specialist will inevitably find inconclusive
      results, and additional testing can contribute to make the appropriate diagnosis.
      Several studies have been published on the effects of reflective testing. Some
      studies focus on the opinion of the general practitioners or other clinicians,
      whereas other studies were intended to determine the patient's perspective.
      Overall, reflective testing was judged as a useful way to improve the process of
      diagnosing (and treating) patients. There is to date scarce high quality
      scientific evidence of the effectiveness of this procedure in terms of patient
      management. A randomized clinical trial investigating this aspect is however
      ongoing. Cost effectiveness of reflective testing still needs to be determined in
      the future. In conclusion, reflective testing can be seen as a new dimension in
      the service of the clinical chemistry laboratory to primary health care.
      Additional research is needed to deliver the scientific proof of the
      effectiveness of reflective testing for patient management.

PMID- 22850058
TI  - The recoveryELISA--a newly developed immunoassay for measurement of therapeutic
      antibodies and the target antigen during antibody therapy.
AB  - Therapeutic antibodies are an important part of Biopharmaceuticals. They are
      highly innovative and specific drugs. Additionally, they play a challenging role
      in new demands in diagnostics because they disturb conventional antibody-based
      tests, such as immunoassays. The recoveryELISA is a newly developed immunoassay
      technology for monitoring such therapeutic antibodies or comparable biologics
      during the therapy. The recoveryELISA determines three results in one test: the
      free level of antigen (if available in serum), the level of therapeutic antibody
      and the specific dose-response interaction. The free level of antigen is the
      amount that can be measured in the immunoassay, as it exists unmasked under assay
      conditions. The relationship between therapeutic antibody level and
      neutralization rate of target protein is shown by the so-called 'recovery curve'.
      The recoveryELISA is demonstrated with the example of Omalizumab/IgE.

PMID- 22850059
TI  - Exploring synergies between academia and vaccine manufacturers: a pilot study on
      how to rapidly produce vaccines to combat emerging pathogens.
AB  - BACKGROUND: In spring 2009, a new swine-origin influenza A (H1N1) virus emerged
      in Mexico. During the following weeks the virus spread worldwide, prompting the
      World Health Organization to declare the first influenza pandemic of the 21st
      century. Sustained human-to-human transmission and severe disease progression
      observed in some patients urged public health authorities to respond rapidly to
      the disease outbreak and vaccine manufacturers to develop pandemic influenza
      vaccines for mass distribution. With the onset of the pandemic we began to
      explore the potential of academic/industrial collaboration to accelerate the
      production of vaccines during an outbreak of an emerging virus by combining the
      use of an academic BSL-4 laboratory with the expertise of a commercial vaccine
      manufacturer. METHODS AND RESULTS: To obtain virus seed stocks used for the
      production of a vaccine to combat the pandemic H1N1 2009 influenza virus
      (H1N1pdm), we followed various strategies: (i) optimization of cell culture
      conditions for growth of wild-type H1N1pdm isolates; (ii) classical reassortment
      of H1N1pdm and standard influenza vaccine donor strain PR8; and (iii) generation
      of corresponding reassortant viruses using reverse genetics. To ensure a rapid
      transition to production, the entire potential seed stock development process was
      carried out in a certified canine kidney suspension cell line (MDCK 33016-PF)
      under Good Manufacturing Practice (GMP) conditions. CONCLUSIONS: The outcome of
      this study indicates that a combination of different experimental strategies is
      the best way to cope with the need to develop vaccines rapidly in the midst of an
      emerging pandemic.

PMID- 22850060
TI  - Estimating the number of one-step beneficial mutations.
AB  - Mutations that confer a selective advantage to an organism are the raw material
      upon which natural selection acts. The number of such mutations that are
      available is a central quantity of interest for understanding the tempo and
      trajectory of adaptive evolution. While this quantity is typically unknown, it
      can be estimated with varying levels of accuracy based on data obtained
      experimentally. We propose a method for estimating the number of beneficial
      mutations that accounts for the evolutionary forces that generate the data. Our
      model-based parametric approach is compared to an adjusted nonparametric
      abundance-based coverage estimator. We show that, in general, our estimator
      performs better. When the number of mutations is small, however, the performances
      of the two estimators are similar.

PMID- 22850061
TI  - How to analyze many contingency tables simultaneously in genetic association
      studies.
AB  - We study exact tests for (2 x 2) and (2 x 3) contingency tables, in particular
      exact chi-squared tests and exact tests of Fisher type. In practice, these tests
      are typically carried out without randomization, leading to reproducible results
      but not exhausting the significance level. We discuss that this can lead to
      methodological and practical issues in a multiple testing framework when many
      tables are simultaneously under consideration as in genetic association
      studies.Realized randomized p-values are proposed as a solution which is
      especially useful for data-adaptive (plug-in) procedures. These p-values allow to
      estimate the proportion of true null hypotheses much more accurately than their
      non-randomized counterparts. Moreover, we address the problem of positively
      correlated p-values for association by considering techniques to reduce
      multiplicity by estimating the "effective number of tests" from the correlation
      structure.An algorithm is provided that bundles all these aspects, efficient
      computer implementations are made available, a small-scale simulation study is
      presented and two real data examples are shown.

PMID- 22850062
TI  - Correction for founder effects in host-viral association studies via principal
      components.
AB  - Viruses such as HIV and Hepatitis C (HCV) replicate rapidly and with high
      transcription error rates, which may facilitate their escape from immune
      detection through the encoding of mutations at key positions within human
      leukocyte antigen (HLA)-specific peptides, thus impeding T-cell recognition.
      Large-scale population-based host-viral association studies are conducted as
      hypothesis-generating analyses which aim to determine the positions within the
      viral sequence at which host HLA immune pressure may have led to these viral
      escape mutations. When transmission of the virus to the host is HLA-associated,
      however, standard tests of association can be confounded by the viral relatedness
      of contemporarily circulating viral sequences, as viral sequences descended from
      a common ancestor may share inherited patterns of polymorphisms, termed 'founder
      effects'. Recognizing the correspondence between this problem and the confounding
      of case-control genome-wide association studies by population stratification, we
      adapt methods taken from that field to the analysis of host-viral associations.
      In particular, we consider methods based on principal components analysis within
      a logistic regression framework motivated by alternative formulations in the
      Frisch-Waugh-Lovell Theorem. We demonstrate via simulation their utility in
      detecting true host-viral associations whilst minimizing confounding by
      associations generated by founder effects. The proposed methods incorporate
      relatively robust, standard statistical procedures which can be easily
      implemented using widely available software, and provide alternatives to the more
      complex computer intensive methods often implemented in this area.

PMID- 22850063
TI  - An integrated hierarchical Bayesian model for multivariate eQTL mapping.
AB  - Recently, expression quantitative loci (eQTL) mapping studies, where expression
      levels of thousands of genes are viewed as quantitative traits, have been used to
      provide greater insight into the biology of gene regulation. Originally, eQTLs
      were detected by applying standard QTL detection tools (using a "one gene at-a
      time" approach), but this method ignores many possible interactions between
      genes. Several other methods have proposed to overcome these limitations, but
      each of them has some specific disadvantages. In this paper, we present an
      integrated hierarchical Bayesian model that jointly models all genes and SNPs to
      detect eQTLs. We propose a model (named iBMQ) that is specifically designed to
      handle a large number G of gene expressions, a large number S of regressors
      (genetic markers) and a small number n of individuals in what we call a ''large
      G, large S, small n'' paradigm. This method incorporates genotypic and gene
      expression data into a single model while 1) specifically coping with the high
      dimensionality of eQTL data (large number of genes), 2) borrowing strength from
      all gene expression data for the mapping procedures, and 3) controlling the
      number of false positives to a desirable level. To validate our model, we have
      performed simulation studies and showed that it outperforms other popular methods
      for eQTL detection, including QTLBIM, R-QTL, remMap and M-SPLS. Finally, we used
      our model to analyze a real expression dataset obtained in a panel of mice BXD
      Recombinant Inbred (RI) strains. Analysis of these data with iBMQ revealed the
      presence of multiple hotspots showing significant enrichment in genes belonging
      to one or more annotation categories.

PMID- 22850064
TI  - A novel and fast normalization method for high-density arrays.
AB  - BACKGROUND: Among the most commonly applied microarray normalization methods are
      intensity-dependent normalization methods such as lowess or loess algorithms.
      Their computational complexity makes them slow and thus less suitable for
      normalization of large datasets. Current implementations try to circumvent this
      problem by using a random subset of the data for normalization, but the impact of
      this modification has not been previously assessed. We developed a novel
      intensity-dependent normalization method for microarrays that is fast, simple and
      can include weighing of observations. RESULTS: Our normalization method is based
      on the P-spline scatterplot smoother using all data points for normalization. We
      show that using a random subset of the data for normalization should be avoided
      as unstable results can be produced. However, in certain cases normalization
      based on an invariant subset is desirable, for example, when groups of samples
      before and after intervention are compared. We show in the context of DNA
      methylation arrays that a constant weighted P-spline normalization yields a more
      reliable normalization curve than the one obtained by normalization on the
      invariant subset only. CONCLUSIONS: Our novel intensity-dependent normalization
      method is simpler and faster than current loess algorithms, and can be applied to
      one- and two-colour array data, similar to normalization based on loess.
      AVAILABILITY: An implementation of the method is currently available as an R
      package called TurboNorm from www.bioconductor.org.

PMID- 22850065
TI  - Incorporating the empirical null hypothesis into the Benjamini-Hochberg
      procedure.
AB  - For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has
      become a very popular method in applications. We show how the B-H procedure can
      be interpreted as a test based on the spacings corresponding to the p-value
      distributions. This interpretation leads to the incorporation of the empirical
      null hypothesis, a term coined by Efron (2004). We develop a mixture modelling
      approach for the empirical null hypothesis for the B-H procedure and demonstrate
      some theoretical results regarding both finite-sample as well as asymptotic
      control of the false discovery rate. The methodology is illustrated with
      application to two high-throughput datasets as well as to simulated data.

PMID- 22850066
TI  - Testing clonality of three and more tumors using their loss of heterozygosity
      profiles.
AB  - Cancer patients often develop multiple malignancies that may be either metastatic
      spread of a previous cancer (clonal tumors) or new primary cancers (independent
      tumors). If diagnosis cannot be easily made on the basis of the pathology review,
      the patterns of somatic mutations in the tumors can be compared. Previously we
      have developed statistical methods for testing clonality of two tumors using
      their loss of heterozygosity (LOH) profiles at several candidate markers. These
      methods can be applied to all possible pairs of tumors when multiple tumors are
      analyzed, but this strategy can lead to inconsistent results and loss of
      statistical power. In this work we will extend clonality tests to three and more
      malignancies from the same patient. A non-parametric test can be performed using
      any possible subset of tumors, with the subsequent adjustment for multiple
      testing. A parametric likelihood model is developed for 3 or 4 tumors, and it can
      be used to estimate the phylogenetic tree of tumors. The proposed tests are more
      powerful than combination of all possible pairwise tests.

PMID- 22850067
TI  - A non-homogeneous dynamic Bayesian network with sequentially coupled interaction
      parameters for applications in systems and synthetic biology.
AB  - An important and challenging problem in systems biology is the inference of gene
      regulatory networks from short non-stationary time series of transcriptional
      profiles. A popular approach that has been widely applied to this end is based on
      dynamic Bayesian networks (DBNs), although traditional homogeneous DBNs fail to
      model the non-stationarity and time-varying nature of the gene regulatory
      processes. Various authors have therefore recently proposed combining DBNs with
      multiple changepoint processes to obtain time varying dynamic Bayesian networks
      (TV-DBNs). However, TV-DBNs are not without problems. Gene expression time series
      are typically short, which leaves the model over-flexible, leading to over
      fitting or inflated inference uncertainty. In the present paper, we introduce a
      Bayesian regularization scheme that addresses this difficulty. Our approach is
      based on the rationale that changes in gene regulatory processes appear gradually
      during an organism's life cycle or in response to a changing environment, and we
      have integrated this notion in the prior distribution of the TV-DBN parameters.
      We have extensively tested our regularized TV-DBN model on synthetic data, in
      which we have simulated short non-homogeneous time series produced from a system
      subject to gradual change. We have then applied our method to real-world gene
      expression time series, measured during the life cycle of Drosophila
      melanogaster, under artificially generated constant light condition in
      Arabidopsis thaliana, and from a synthetically designed strain of Saccharomyces
      cerevisiae exposed to a changing environment.

PMID- 22850068
TI  - Effects of participation vs. observation of a simulation experience on testing
      outcomes: implications for logistical planning for a school of nursing.
AB  - The simulation program within our nursing curriculum covers a wide array of
      content areas and has been rated very highly by students and faculty. Due to this
      success, requests for increased simulation experiences have grown dramatically.
      The challenge lies, however, in logistically accommodating large student groups
      in finite periods of time. To overcome these constraints, an alternative plan was
      devised where half of the students actively participate in the simulation while
      their cohort observes. Both groups participate in the debriefing process.
      Findings revealed no significant differences (p=.97) between the simulation and
      observational groups on scoring of the test items related to this content (n=92).
      Over 70% reported the simulation experience as enjoyable, well-organized,
      clarified issues, increased knowledge and prepared them to work in a hospital.
      These findings indicate that the use of this alternate plan was effective for
      student learning and could therefore be incorporated into the simulation program
      design.

PMID- 22850069
TI  - Outcomes of modified formal online debating in graduate nursing education.
AB  - Formal debating is a process for argumentation with a long history of use in
      classroom settings to promote students' development of skills associated with
      influencing others. In an online, 14-week, MN nursing course, modified formal
      debate procedures and rules were used to address contemporary issues in nursing.
      A qualitative descriptive study of student's reflections about engaging in the
      debate process was conducted involving 24 of 48 students representing three
      sections of this course taught by three professors during the 2009-2010 academic
      year. On analysis, the data revealed five categories of outcomes: 1) Risk Taking;
      2) Defence of a Position; 3) Coverage of all Aspects; 4) Skill and Knowledge
      Transfer; and 5) Critical Thinking. Additionally, factors that influenced each of
      these outcomes are described. Study findings support the compelling benefits of
      debating in online learning environments using a format modified for use online.

PMID- 22850070
TI  - Glucosinolates: the phytochemicals of nutraceutical importance.
AB  - Glucosinolates (thioglucoside-N-hydroxysulphates) constitute a homogeneous class
      of naturally occurring thiosaccharidic compounds mainly found in the botanical
      order Brassicales. They can be hydrolyzed by myrosinase to produce D-glucose and
      various other degradation products like isothiocyanates (ITCs)-depending on the
      aglycon part. The exact function of glucosinolates (GLSs) in the plant is
      unclear, however their potent odour and taste suggests a role in herbivore and
      microbial defense. They are known for their fungicidal, bacteriocidal,
      nematocidal and allelopathic properties and have recently attracted intense
      research interest because of their cancer chemo-protective attributes. Iso
      thiocyanates, one of the hydrolyzed products, show best anti-carcinogenic
      activity.

PMID- 22850071
TI  - Efficacy of Baptisia tinctoria in the treatment of typhoid: its possible role in
      inducing antibody formation.
AB  - Typhoid is one of the most serious infectious bacterial diseases in third world
      countries. It is usually treated by traditional antibiotics but due to the
      appearance of antibiotic resistant strains physicians opt for phyto products and
      other alternative medicines for the treatment of typhoid. Baptisia, an extract
      from indigo plant root, has been proved to be highly effective ultradilute
      medicine for the treatment of typhoid; however, the mode of action of the
      ultradilute extract is uncertain. Due to the antigenic variations of Salmonella
      it seems to induce immuno system by activating both T and B cells by the
      formation of antibodies. This principle seems to be highly effective for the
      development of typhoid vaccine. The present studies found that Baptisia
      administration possibly caused a salmonella-like reaction in the body as this
      extract produces an endogenous antibody similar to salmonella reaction. Thus,
      this study suggests that Baptisia tinctoria extract can be used for the
      prevention and treatment of typhoid.

PMID- 22850072
TI  - Lycopene an adjunctive therapy for Helicobacter pylori eradication: a quasi
      control trial.
AB  - Although some herbal remedies in association with vitamin therapy have been
      investigated in eradicating HP, no research has been done to investigate the
      effects of lycopene it. Our aim was to understand if lycopene could be effective
      in eradication of HP. In this parallel group quasi-control trial, a total of 54
      patients whose diagnosis of HP had been confirmed by rapid urease test (RUT) were
      enrolled. Group 1 received the standard 4-drug therapy to eradicate HP
      (Metronidazole 500 mg/BD, Amoxicillin 1g/BD, Omeprazole 20mg/BD, and Bismuth 240
      mg/BD) and group 2 received the same regimen in association with Lycopene (30
      mg/daily). One month after the initiation of the treatment, the patients were
      evaluated for HP eradication by RUT. Although eradication rate was higher in the
      second group, bivariate analysis showed no significant statistical difference
      between the two groups. In contrast with other nutrients, it seems that Lycopene
      does not have any significant effects on eradicating HP in comparison with the
      standard antibiotic therapy. The prevalence of HP is in association with
      socioeconomic situation, so the patients in different studies should be paid more
      attention about their own life style. We recommend that more studies can be
      designed by considering control group and placebo administration.

PMID- 22850073
TI  - Statistical issues and limitations in personalized medicine research with
      clinical trials.
AB  - We discuss using clinical trial data to construct and evaluate rules that use
      baseline covariates to assign different treatments to different patients. Given
      such a candidate personalization rule, we first note that its performance can
      often be evaluated without actually applying the rule to subjects, and a class of
      estimators is characterized from a statistical efficiency standpoint. We also
      point out a recently noted reduction of the rule construction problem to a
      classification task and extend results in this direction. Together these facts
      suggest a natural form of cross-validation in which a personalized medicine rule
      can be constructed from clinical trial data using standard classification tools
      and then evaluated in a replicated trial. Because replication is often required
      by the FDA to provide evidence of safety and efficacy before pharmaceutical drugs
      can be marketed, there are abundant data with which to explore the potential
      benefits of more tailored therapy. We constructed and evaluated personalized
      medicine rules using simulations based on two active-controlled randomized
      clinical trials of antibacterial drugs for the treatment of skin and skin
      structure infections. Unfortunately we present negative results that did not
      suggest benefit from personalization. We discuss the implications of this finding
      and why statistical approaches to personalized medicine problems will often face
      difficult challenges.

PMID- 22850074
TI  - Measures of family resemblance for binary traits: likelihood based inference.
AB  - Detection and estimation of measures of familial aggregation is considered the
      first step to establish whether a certain disease has genetic component. Such
      measures are usually estimated from observational studies on siblings, parent
      offspring, extended pedigrees or twins. When the trait of interest is
      quantitative (e.g. Blood pressures, body mass index, blood glucose levels, etc.)
      efficient likelihood estimation of such measures is feasible under the assumption
      of multivariate normality of the distributions of the traits. In this case the
      intra-class and inter-class correlations are used to assess the similarities
      among family members. When the trail is measured on the binary scale, we
      establish a full likelihood inference on such measures among siblings, parents,
      and parent-offspring. We illustrate the methodology on nuclear family data where
      the trait is the presence or absence of hypertension.

PMID- 22850075
TI  - "Imagine a can opener"--the magic of principal stratum analysis.
AB  - Abstract     We extend Pearl's criticisms of principal stratification analysis as
      a method for interpreting and adjusting for intermediate variables in a causal
      analysis.  We argue that this can be meaningful only in those rare cases that
      involve strong functional dependence, and even then may not be appropriate.

PMID- 22850076
TI  - Testing the assumptions for the analysis of survival data arising from a
      prevalent cohort study with follow-up.
AB  - In a prevalent cohort study with follow-up subjects identified as prevalent cases
      are followed until failure (defined suitably) or censoring. When the dates of the
      initiating events of these prevalent cases are ascertainable, each observed datum
      point consists of a backward recurrence time and a possibly censored forward
      recurrence time. Their sum is well known to be the left truncated lifetime. It is
      common to term these left truncated lifetimes "length biased" if the initiating
      event times of all the incident cases (including those not observed through the
      prevalent sampling scheme) follow a stationary Poisson process. Statistical
      inference is then said to be carried out under stationarity. Whether or not
      stationarity holds, a further assumption needed for estimation of the incident
      survivor function is the independence of the lifetimes and their accompanying
      truncation times. That is, it must be assumed that survival does not depend on
      the calendar date of the initiating event. We show how this assumption may be
      checked under stationarity, even though only the backward recurrence times and
      their associated (possibly censored) forward recurrence times are observed. We
      prove that independence of the lifetimes and truncation times is equivalent to
      equality in distribution of the backward and forward recurrence times, and
      exploit this equivalence as a means of testing the former hypothesis. A
      simulation study is conducted to investigate the power and Type 1 error rate of
      our proposed tests, which include a bootstrap procedure that takes into account
      the pairwise dependence between the forward and backward recurrence times, as
      well as the potential censoring of only one of the members of each pair. We
      illustrate our methods using data from the Canadian Study of Health and Aging. We
      also point out an equivalence of the problem presented here to a non-standard
      changepoint problem.

PMID- 22850077
TI  - Targeted minimum loss based estimation of a causal effect on an outcome with
      known conditional bounds.
AB  - This paper presents a targeted minimum loss based estimator (TMLE) that
      incorporates known conditional bounds on a continuous outcome. Subject matter
      knowledge regarding the bounds of a continuous outcome within strata defined by a
      subset of covariates, X, translates into statistical knowledge that constrains
      the model space of the true joint distribution of the data. In settings where
      there is low Fisher Information in the data for estimating the desired parameter,
      as is common when X is high dimensional relative to sample size, incorporating
      this domain knowledge can improve the fit of the targeted outcome regression,
      thereby improving bias and variance of the parameter estimate. We show that TMLE,
      a substitution estimator defined as a mapping from a density to a (possibly d
      dimensional) real number, readily incorporates this global knowledge, resulting
      in improved finite sample performance.

PMID- 22850078
TI  - Comparison of single and split-dose flubendazole treatment for the nematode
      parasite Trichostrongylus tenuis in experimentally infected grey partridges
      Perdix perdix.
AB  - Different therapeutic regimes using flubendazole for the treatment of
      Trichostrongylus tenuis infection in experimentally infected grey partridges
      Perdix perdix were examined. Flubendazole dosages of 4, 8 and 20 mg/kg were
      administered orally as a single dose or split into 3 or 9 parts given over 9
      days. The efficacy against adult worms in the caeca improved with dose rate.
      Split doses were at least as effective as single doses, which removed up to 83%
      of adult T. tenuis. A dose of 20 mg/kg administered on a daily basis over 3 or 9
      days gave the best clearance of T. tenuis, resulting in a reduction of at least
      95% in worm burden.

PMID- 22850079
TI  - Casein glycomacropeptide in the diet may reduce Escherichia coli attachment to
      the intestinal mucosa and increase the intestinal lactobacilli of early weaned
      piglets after an enterotoxigenic E. coli K88 challenge.
AB  - Casein glycomacropeptide (CGMP), a glycoprotein originating during cheese
      manufacture, has shown promising effects by promoting the growth of some
      beneficial bacteria in vitro, although its activity has not been well explored.
      The present study was designed to evaluate the effects of CGMP against
      enterotoxigenic Escherichia coli (ETEC) K88 in vitro (Trial 1) and in vivo (Trial
      2). In Trial 1, increasing concentrations of CGMP (0, 0.5, 1.5 or 2.5 mg/ml) were
      tested regarding its ability to block the attachment of ETEC K88 to ileal mucosa
      tissues obtained from piglets. Increasing the concentration of CGMP resulted in a
      gradual decrease in ETEC K88 attachment to the epithelial surface. In Trial 2,
      seventy-two piglets were distributed in a 2 * 2 factorial combination including
      or omitting CGMP in the diet (control diet v. CGMP) and challenged or not with
      ETEC K88 (yes v. no). Inclusion of CGMP increased crude protein, ammonia and
      isoacid concentrations in colon digesta. CGMP also increased lactobacilli numbers
      in ileum and colon digesta, and reduced enterobacteria counts in mucosa scrapings
      and the percentage of villi with E. coli adherence measured by fluorescence in
      situ hybridisation. The inclusion of CGMP in the diets of challenged animals also
      prevented the increase of enterobacteria in ileal digesta. We can conclude that
      CGMP may improve gut health by diminishing the adhesion of ETEC K88 to the
      intestinal mucosa, by increasing the lactobacilli population in the intestine and
      by reducing the overgrowth of enterobacteria in the digestive tract of piglets
      after an ETEC K88 challenge.

PMID- 22850080
TI  - Psychological functioning and adherence to the recommended dose of physical
      activity in later life: results from a national health survey.
AB  - BACKGROUND: Official health organizations have established the dose of physical
      activity needed for preserving both physical and psychological health in old age.
      The objective of this study was to explore whether adherence to the recommended
      criterion of physical activity accounted for better psychological functioning in
      older adults in Israel. METHODS: A random sample of 1,663 (799 men) Israelis
      reported their physical activity routine, and based on official guidelines were
      divided into sufficiently active, insufficiently active, and inactive groups. The
      General Health Questionnaire (GHQ) was used for assessing mental health and the
      Mini-Mental State Examination (MMSE) for assessing cognitive functioning.
      RESULTS: Factor analysis performed on the GHQ yielded two factors - positive and
      negative. Logistic regressions for the GHQ factors and for the MMSE were
      conducted for explaining their variance, with demographic variables entered
      first, followed by health and then physical activity. The explained variance in
      the three steps was Cox and Snell R2 = 0.022, 0.023, 0.039 for the positive
      factor, 0.066, 0.093, 0.101 for the negative factor, and 0.204, 0.206, 0.209 for
      the MMSE. CONCLUSIONS: Adherence to the recommended dose of physical activity
      accounted for better psychological functioning beyond demographic and health
      variables; however, the additional explained variance was small. More specific
      guidelines of physical activity may elucidate a stronger relationship, but only
      randomized controlled trials can reveal cause-effect relationship between
      physical activity and psychological functioning. More studies are needed focusing
      on the positive factor of psychological functioning.

PMID- 22850081
TI  - A two-dimensional liquid-filled ionization chamber array prototype for small
      field verification: characterization and first clinical tests.
AB  - In this work we present the design, characterization and first clinical tests of
      an in-house developed two-dimensional liquid-filled ionization chamber prototype
      for the verification of small radiotherapy fields and treatments containing such
      small fields as in radiosurgery, which consists of 2 mm * 2 mm pixels arranged on
      a 16*8 rectangular grid. The ionization medium is isooctane. The characterization
      of the device included the study of depth, field-size and dose-rate dependences,
      which are sufficiently moderate for a good operation at therapy radiation levels.
      However, the detector presents an important anisotropic response, up to ? 12% for
      front versus near-lateral incidence, which can impact the verification of full
      treatments with different incidences. In such a case, an anisotropy correction
      factor can be applied. Output factors of small square fields measured with the
      device show a small systematic over-response, less than 1%, when compared to
      unshielded diode measurements. An IMRT radiosurgery treatment has been acquired
      with the liquid-filled ionization chamber device and compared with film dosimetry
      by using the gamma method, showing good agreement: over 99% passing rates for
      1.2% and 1.2 mm for an incidence-per-incidence analysis; 100% passing rates for
      tolerances 1.8% and 1.8 mm when the whole treatment is analysed and the
      anisotropy correction factor is applied. The point dose verification for each
      incidence of the treatment performed with the liquid-filled ionization chamber
      agrees within 1% with a CC01 ionization chamber. This prototype has shown the
      utility of this kind of technology for the verification of small
      fields/treatments. Currently, a larger device covering a 5 cm * 5 cm area is
      under development.

PMID- 22850082
TI  - Infant abusive head trauma incidence in Queensland, Australia.
AB  - This study describes the incidence of head injuries caused by abuse in an
      Australian infant sample. The frequency of abusive head trauma established by the
      study is comparable with that reported both internationally and for age-incidence
      peaks of alternate forms of childhood injury, highlighting the need for
      investment in prevention initiatives.

PMID- 22850083
TI  - On preventing all injuries.

PMID- 22850084
TI  - The challenges of implementing interlock best practices in a federal state: the
      Canadian experience.

PMID- 22850085
TI  - Child Safety Report Cards: inconsistency in policy adoption across 31 countries.
      Countries need to increase adoption of proven child safety policies to protect
      Europe's most vulnerable citizens and future society.

PMID- 22850086
TI  - New diploma in emergency medicine in France:  the students' perspective.
AB  - French emergency medicine (EM) has undergone rapid changes with the establishment
      of a diploma in emergency medicine (DES). We aimed to question medicine students
      on their knowledge of and apprehensions regarding this new DES. We conducted an
      email cross-sectional survey among second-cycle medical students before their
      choice of resident speciality. This included a demographic study and an
      evaluation of the willingness to choose emergency specialization. Two thousand
      and three fully completed questionnaires were analysed. Twenty-six per cent of
      the students (n=524) planned to choose emergency specialization and 54% of the
      students (n=1084) knew that emergency specialization would be proposed as a full
      speciality. Seventy-six per cent of students considered it tough to practice as
      an entire career. This study clearly shows that EM represents an attractive
      option for medical students. The establishment of DES represents a major step in
      the improvement of EM.

PMID- 22850087
TI  - Five-year trends in self-reported recreational drugs associated with presentation
      to a UK emergency department with suspected drug-related toxicity.
AB  - OBJECTIVE: User surveys show that there have been significant changes over the
      last decade in the recreational drugs that are available and being used. This
      study aims to determine whether there have been similar trends in the drug(s)
      used by individuals presenting to the emergency department (ED) with acute
      recreational drug toxicity. METHODS: Data on all poisoned patients presenting to
      our large inner-city ED are recorded prospectively on a dedicated clinical
      toxicology database. Presentations relating to the use of classical recreational
      drugs and/or novel psychoactive substances were identified retrospectively
      between 1 January 2006 and 31 December 2010. RESULTS: There was a significant
      increase between 2006 and 2010 in the number of individuals reporting the use of
      cocaine (119-222), gamma-hydroxybutyrate/gamma-butyrolactone (158-270), ketamine
      (58-81) and cannabis (18-68) and novel psychoactive substances (seven to 98). In
      particular, there was an increase in cathinones reported from none in 2006 to 82
      in 2010. Only 3,4-methylenedioxymethamphetamine (MDMA) was associated with a
      downward trend in reported use from 140 in 2006 to 103 in 2010. CONCLUSION: Data
      collection on the drug(s) used in individuals presenting to specialist clinical
      toxicology centres and/or sentinel EDs across Europe with acute recreational drug
      toxicity would help to determine the true pattern(s) of drug use and the acute
      harm associated with this use across Europe and trends over time.

PMID- 22850088
TI  - The relationship between trauma mechanism, fracture type, and treatment of
      midshaft clavicular fractures.
AB  - OBJECTIVE: The debate on whether midshaft clavicular fractures should preferably
      be treated operatively or nonoperatively still continues. Several patient-related
      factors may influence this treatment decision. A retrospective study was carried
      out to determine the relation between fracture type and trauma mechanism, age and
      sex, and the influence of these factors on the choice of primary treatment.
      METHODS: Data on the trauma mechanism and treatment of 232 adult patients, who
      presented with a midshaft clavicular fracture in two hospitals in the Netherlands
      during the years 2006-2009, were collected. The extent of clavicular shortening,
      displacement, and fracture type on the primary radiograph were scored. RESULTS:
      Traffic accidents are the main cause of midshaft clavicular fractures. After
      correction for age, no relation was found between the trauma mechanism and the
      fracture type. Older age correlated with more comminuted and displaced fractures.
      Extensive shortening (>20 mm) was identified as the main clinical indication for
      primary surgery, whereas displacement and fracture classification seemed less
      relevant. Operative treatment was increasingly favored from 5% in 2006 to 44% in
      2009, which could not be explained by an increase in more complex fractures or by
      age-related or trauma mechanism-related factors. CONCLUSION: Age has a major
      influence on the fracture type, whereas the trauma mechanism does not. The choice
      for the surgical treatment of midshaft clavicular fractures is primarily
      determined by the amount of axial shortening of the clavicle, rather than by the
      overall displacement or fracture type. Over the years, the choice of treatment
      seems to have been increasingly influenced by the patient's and surgeon's
      preferences.

PMID- 22850089
TI  - Ambulance personnel adherence to hygiene routines: still protecting ourselves but
      not the patient.
AB  - OBJECTIVES: It is well known that adherence to hygiene routines leads to
      increased quality of care and safety for patients and personnel in hospitals.
      However, there have been few studies describing hygiene in ambulances, despite
      the fact that many patients receive advanced medical care and treatment from
      ambulance services before arriving at an emergency department. Therefore, the
      purpose of this study was to describe the adherence of ambulance personnel to
      hygiene routines in the ambulances. METHODS: A participant observation study in
      the County of Varmland (Sweden) was conducted over 1 day in November 2010. Seven
      hygiene-related variables were collected during the observations: disinfection of
      hands before and after patient contact; correct use of gloves, gowns and short
      sleeved uniforms; no rings, watches, or bracelets; and short or tied back hair
      during patient care. RESULT: A total of 68 observed ambulance assignments were
      analyzed in terms of the adherence of personnel to hygiene routines. In 34% of
      the observed cases, hand rub was used before patient care and, in 72% of the
      observed cases, the ambulance personnel used hand rub after patient care. Correct
      adherence to the rule requiring use of a short-sleeved uniform was found in 28%
      of the observations. Correct adherence to the rule regarding short or tied back
      hair was found in 91% of the observations. CONCLUSION: The ambulance personnel
      were found to have relatively good adherence to some hygiene routines, but not
      all. The adherence by ambulance personnel to all of the seven observed variables
      was correct in only 3% of the assignments.

PMID- 22850090
TI  - Hyponatremia is the valuable manifestation for initiating diagnosis of
      hypopituitarism in elderly.
AB  - The present study was undertaken to determine clinical features of
      hypopituitarism in elderly subjects.  Thirty-one elderly patients with
      hypopituitarism were enrolled.  They were 19 males and 12 females, with the ages
      of 70.7+/-5.4 years ranging from 62 to 80 years.  High prevalence of hyponatremia
      (80.6%) and hypoglycemia (29.0%) was found, and it was totally different from
      that in hypopituitarism from general population.  There were two groups of
      hyponatremia derived from their clinical courses, namely, acute deterioration of
      hyponatremia and chronically persistent hyponatremia.  Analysis for deficient
      hormones clearly showed that ACTH deficiency was highly found in 30 of 31
      patients.  There was no difference in serum cortisol levels between the
      hyponatremic and normonatremic patients.  Despite hypoosmolality, plasma arginine
      vasopressin (AVP) was apparently high in the hyponatremic patients compared with
      in the normonatremic ones.  The present study indicates that hyponatremia is the
      valuable finding for initiating diagnosis of hypopituitarism, and that augmented
      release of AVP may be involved in developing hyponatremia in elderly patients
      with hypopituitarism.

PMID- 22850091
TI  - Video-assisted thoracoscopic thymectomy (VAT-T) with lateral thoracotomy for
      stage II and III thymoma.
AB  - Thymoma has malignant potential and is the most common anterior mediastinal
      tumor. Video-assisted thoracic surgery (VATS), which is less invasive surgical
      procedure, is a good option for resecting Masaoka stage I tumors. Whether VATS is
      appropriate, depends on the surgeon's judgment and accurate imaging diagnosis. We
      introduce a technique involving a combination of video-assisted thoracoscopic
      thymectomy (VAT-T) and lateral thoracotomy for stage II and some stage III
      thymomas that have locally invaded the lung and/or pericardium.

PMID- 22850092
TI  - Prosthetic valve endocarditis after double valve replacement with the Manouguian
      procedure.
AB  - Prosthetic valve endocarditis is a rare but severe complication after double
      mitral and aortic valve replacement. It is debated whether or not all prostheses
      should be replaced simultaneously, because of high operative mortality with redo
      double valve replacement. We report a case of prosthetic valve endocarditis after
      double mitral and aortic valve replacement with the Manouguian procedure. A 56
      year-old man had undergone double valve replacement 12 years prior and presented
      with high fever 2 months after dental treatment. Enterococcus faecalis was
      isolated from blood cultures twice. Transthoracic echocardiography showed
      perivalvular mitral regurgitation, but no vegetations or abscess. Transesophageal
      echocardiography revealed an abscess on the aortomitral continuity of the
      Manouguian patch. We removed all previous prostheses and performed redo aortic
      and mitral valve replacements with a repeat Manouguian procedure. The
      postoperative course was satisfactory. Precise preoperative evaluation by
      transesophageal echocardiography and radical removal of the infected prostheses
      resulted in successful treatment.

PMID- 22850093
TI  - Emergency repair of acute aortic dissection in a patient with relapsing
      polychondritis.
AB  - Relapsing polychondritis (RP) is a rare, inflammatory, multiorgan disorder
      affecting cartilaginous structure and other connective tissue. Cardiovascular
      complications occur in 10%-52% of patients. We report a case of emergency surgery
      for an acute aortic dissection in a patient with RP. A 45-year-old female who had
      been taking corticosteroids (10 mg/day) for 2 years for RP presented at another
      hospital with dyspnea and severe chest and back pain. Acute aortic dissection was
      diagnosed, and we performed emergency replacement of the ascending aorta. We
      could not control the bleeding from suture holes of the native aorta because the
      vessel was so fragile. Thus, we performed a delayed sternal closure. The day
      after surgery, bleeding had decreased, and we could close the chest wall.
      Infection was well controlled, and the patient suffered minimal additional
      complications. She was discharged to home by herself 29 days after surgery and
      returned to normal life.

PMID- 22850094
TI  - Paraesophageal hernia repair.
AB  - Paraesophageal hiatal hernia (PHH), accounting for only 5% of all hiatal hernias,
      may result in potentially life threatening complications such as obstruction,
      acute dilatation, perforation, or bleeding of the gastric mucosa. It is
      traditionally believed that PHH is an indication for surgery. The repair of
      paraesophageal hernia is technically challenging and controversial. The purpose
      of this article is to overview the current status of indication of surgery;
      operative techniques including hernia sac resection, esophageal lengthening
      procedure, crural repair, and additional antireflux procedure. RESULTS: All
      symptomatic patients should be surgically treated, when operation is possible. It
      seems reasonable that asymptomatic or minimally symptomatic patients do not
      necessarily require surgery and that a more selective approach should be used.
      The penetration rate is not high, laparoscopic approach is currently the standard
      care. The hernia sac should be excised and resected circumferentially. Collis
      Nissen procedure continues to be the method of choice also in the laparoscopic
      era, when lengthening procedure of the shortened esophagus is in consideration.
      Although symptomatic recurrence after suture closure of the crura is uncommon,
      primary repair is associated with a high rate of anatomic recurrence. Prosthetic
      mesh repair is reportedly associated with a recurrence rate as low as 5%, at the
      price of rare but serious complications such as erosion and fibrosis. Although
      scientific proof is lacking, fundoplication is the most common procedure to be
      added after crural repair.

PMID- 22850095
TI  - [The adoption of Jarde law modifies the legal framework of clinical research in
      France].
AB  - The Jarde law is adopted further to the Public Health Act No. 2004-806 which
      transposed into French law the Directive 2001/20/EC on clinical trials of
      medicinal products, made effective by the implementing Decree 2006-477 of April
      26, 2006. The main novelty introduced by the Jarde law is to unify all "research
      organized and practiced on human beings for the development of biological or
      medical knowledge" and to facilitate its effective conduct, without however
      excluding from the scope of the law routine care and non-interventional research.
      The favorable opinion of the French Ethical Research Committee (comite de
      protection des personnes or "CCP") will now be required before launching any
      research on human beings, after validation of the risk/benefit ratio of said
      research. Applicable requirements and procedures - including information and
      consent - are adapted to each category of clinical research. New provisions are
      adopted to address special situations, previously forgotten. Finally, if Ethics
      committees were up until now freely chosen, they will, in two years' time, be
      randomly assigned. Thus, the Jarde law amends substantially the legal framework
      of clinical research in France. The question is whether these new national
      provisions will be compatible with those from the next revision of the so called
      "clinical trials" directive 2001/20/EC. In any case, the Jarde law will only come
      into force when all required implementing measures have been adopted.

PMID- 22850096
TI  - [The investment of pharmaceutical industry in hospital clinical research: an
      estimate for france in 2010].
AB  - The objective of this study was to estimate the investment of pharmaceutical
      industry in hospital clinical research in France for 2010. The method consisted
      in combining data extracted from various sources about volumes of patients and
      unit costs per patient according to phase (I, II and II) and therapeutic domains.
      The numbers of French patients enrolled were estimated through an extraction of
      the National Institute of Health (NIH) database. Unit costs per patient were
      estimated from a sample of 54 clinical studies covering the most frequent
      combinations of phases and therapeutic domains and documented independently by 5
      international companies. We identified 1, 178 clinical studies ongoing in 2010,
      having included a total of about 73, 000 French patients. Among these studies,
      40.3% and 12.8% concerned Onco-Haematology and Rare Diseases respectively. The
      total annual investment from industry was estimated at 488 million euros,
      comprising 83.6 M? of medical honoraria (17%), 73 M? of hospital extra cost
      (15%), 99 M? of drug provision (20%) and 232 M? of internal cost for french
      affiliates (48%).

PMID- 22850097
TI  - [Anatomy of the CMRR and proposition of functioning].
AB  - OBJECTIVES: The main objective was to have a view of the functioning of the
      Centers Memory of Resources and Research (CMRR) to identify the difficulties
      which can interfere in the industrial clinical trials. The secondary objective
      was to make a proposal to optimize them. METHODOLOGY: Questionnaires were given
      in all CMRRs. RESULTS: One hundred thrity-five questionnaires were retrived (26
      centers answered on the 27 that exist). Some elements appeared as strong
      structural factors but some weaknesses were highlighted such as: insufficient
      staff, lack of dedicated areas, lack of communication, activities
      multiplications, functional unit (UF) subdivision. CONCLUSION-PROPOSITION: After
      a Strenghts-Weakness-Opportunities-Threats (SWOT) analysis, we kept 3 main axis
      to improve: information and formation diffusion, transdisciplinary meetings
      establishment, better mobilization of doctors for clinical trials. We think that
      a special "clinical trail" unit within each CMRR should be created. It will
      enhance the level, the competences and the reactivtity of each clinical trial
      center which will lead to better collaboration with big pharmaceutical companies.

PMID- 22850098
TI  - [Analysis of prescriptions associated to hormone replacement therapy in Midi
      Pyrenees region].
AB  - The aim of the present study was 1- to describe hormone replacement therapy (HRT)
      prescription in Midi-Pyrenees region (South West France) and 2- to compare the
      prescriptions of associated drugs to those of women who took HRT with
      prescriptions to women who did not take HRT. From 2004 to 2008, HRT prescription
      decreased for women aged 50 to 59 years in Midi-Pyrenees: 13.95% to 10.33%
      estradiol/progestin association consumers. During the first 6 months of 2008,
      20,161 women took the association estradiol/progestin. Transdermal/percutaneous
      forms of estradiol (71.21%) and natural progesterone were mainly prescribed. The
      number of different dispensed drugs was significantly higher in the HRT group:
      5.18 versus 2.82 in the control group (p < 0.0001). All classes were concerned
      except antineoplastic drugs and immunomodulators, drugs for diabetes and
      raloxifene which were more prescribed to controls. In the period of the study,
      7,035 patients took estrogen alone (25.87% of HRT consumers). The same phenomena
      were observed in this group. Women exposed to HRT in Midi-Pyrenees, great
      consumers of drugs, represent a population who require particular medical
      supervision, because of the risks of HRT and pathologies and/or numerous
      associated drugs.

PMID- 22850099
TI  - [National and regional market penetration rates of generic's high dosage
      buprenorphine: its evolution from 2006 to 2008, using reimbursed drug database].
AB  - OBJECTIVE: To assess the national market penetration rate (PR) of generic high
      dosage buprenorphine (HDB) in 2008 and its evolution since their marketing
      (2006), and making a point for each dosage and at regional level. METHODS:
      Retrospective study over data using national and regional health reimbursement
      database over three years (2006-2008). RESULTS: In 2008, the generic HDB's
      national MPR was 31%. The PR for each dosage were 45% for 0.4 mg, 36% for 2 mg
      and 19% for 8 mg. The (PR) based on Defined Daily Dose (DDD) was 23% in 2008, 15%
      in 2007 and 4% in 2006. In 2008, at the regional level, disparities were observed
      in the adjusted penetration rate from 15% in Ile de France to 39% in Champagne
      Ardennes Lorraine. CONCLUSION: The national PR of generic HDB has increased.
      There are differences in MPR in terms of dosage and area. However, this PR is
      still low (in 2008, 82% of the delivered drugs are generics).

PMID- 22850100
TI  - [Patient's medicine cabinet composition study of 207 families in France].
AB  - France is the first country in Europe for medicines' consumption. It is not
      possible to imagine a house without a medicine cabinet. There are very few data
      on this subject. The aim of our work was to study the composition of families'
      cabinets. On the first six month 2010, an investigation questionnaire was
      distributed in pharmacy community located Pyrenees-Atlantiques area.
      Questionnaires were given to all the patients coming to the chemist's. On 207
      questionnaires available, a medicines' cabinet hold 12.1 +/- 12.1 specialities
      name in average, 19.8 +/- 17.9 packing (most frequent: Classes V: miscelleanous
      and A medicines: digestive system and metabolism) and an average of 5.6 +/- 7.5
      expired packing (28.4% of the medicines stock). The present study highlights the
      important quantity of medicines found in the families' medicines cabinets. It
      underlines the important role of the pharmacist and family doctor for the
      patient's therapeutic education.

PMID- 22850101
TI  - [Level of evidence for therapeutic drug monitoring of ceftriaxone].
AB  - Ceftriaxone is a third generation cephalosporin with an original pharmacokinetics
      based on a long elimination half-life among cephalosporins, a high protein
      binding and a dual renal and biliary elimination. Also the pharmacokinetic
      parameters of ceftriaxone are highly variable in clinical situations such as
      severe renal insufficiency, liver and renal insufficiency, the elderly, the
      neonates less than 1 week of age and critically ill patients. In these clinical
      situations associated or not with high minimal inhibitory concentration (MIC)
      level, the relationship concentration-clinical outcome based on the ratio between
      trough plasma concentration and MIC can allow a dose adjustment. Consequently,
      therapeutic drug monitoring (TDM) of ceftriaxone could be possibly useful in
      these situations, whereas the necessity of TDM has still to be demonstrated to
      monitor toxicity.

PMID- 22850102
TI  - [Therapeutic drug monitoring of lacosamide].
AB  - Lacosamide is a third generation antiepileptic drug, available in France since
      2008. It is indicated in combination therapy for the treatment of inadequately
      controlled focal seizures, from the age of 16. The bioavailability of lacosamide
      is 100% and is unaffected by food intake; protein binding is low; it is
      metabolized by CYP2C19 into inactive O-desmethyl lacosamide. It does not inhibit
      or induce cytochromes; the elimination is renal with a half-life of approximately
      13 h. The relationship between dose and plasma concentration is established, but
      there does not appear to be any clear relationship between concentration and
      efficacy. However, the main side effects are concentration dependent. The
      potential for drug-drug interaction of lacosamide is low and variability between
      individuals is minimal. Accordingly, the level of evidence for the therapeutic
      drug monitoring has been estimated at "probably of no use".

PMID- 22850103
TI  - [Therapeutic drug monitoring of stiripentol].
AB  - Stiripentol is a third generation antiepileptic, marketed since 2007 under the
      name of Diacomit((r)). It is indicated, always in combination, in the treatment
      of severe myoclonic epilepsy in infancy or Dravet syndrome. Its pharmacokinetics
      is not linear. It is a potent inhibitor of CYP3A4, 1A2 and 2C19 and increases the
      plasma concentrations of many other antiepileptic drugs. Without this being
      considered as a validated therapeutic range, the trough plasma concentrations at
      steady-state, corresponding to the usual doses are between 10 and 15 mg/L. The
      concentration-efficacy relationship is not established, but there is some
      evidence for a concentration-related toxicity. However, because of its non-linear
      kinetics, stiripentol should be a good candidate for therapeutic drug monitoring
      (TDM). Nonetheless, the current level of evidence for the advantage of TDM is
      "remains to be estimated".

PMID- 22850104
TI  - [Therapeutic drug monitoring of rufinamide].
AB  - Rufinamide is a third-generation antiepileptic drug, available since early 2010
      in France. It is indicated in combination therapy in the Lennox-Gastaut syndrome
      from the age of 4. It has orphan drug status. The bioavailability of rufinamide
      is high, but decreases with the dose and increases with food intake. Rufinamide
      is not metabolized by cytochromes but hydrolyzed by a carboxylesterase in an
      inactive carboxylic derivative. Elimination is mainly renal. The half-life varies
      from 6 to 10h. Although established from relatively few studies, exposure
      efficacy and exposure toxicity relationships are argued. A plasma concentration
      of 15 mg/L, obtained with a standard regimen, reduces the number of seizures of
      25%. Few factors of intrinsic variability are described. There are few clinically
      significant pharmacokinetic interactions and they concern combinations with other
      antiepileptic drugs, especially valproate. Although there is no validated
      therapeutic range, the level of evidence for this therapeutic drug monitoring has
      been estimated at "possibly useful".

PMID- 22850105
TI  - [Diagnostic of pharmacodependence: comparison between patients and doctors
      approaches. Introduction].
AB  - The aim of our study is to evaluate the extent of agreement between
      pharmacodependence  to benzodiazepines, as diagnosed by doctors and as self
      evaluated by patients, using DSM-IV dependence criteria. Method. This is a
      prospective study. INCLUSION CRITERIA: prescription of a benzodiazepines or
      related substances. DATA COLLECTION: doctor questionnaire and patient
      questionnaire filled anonymously and independently. Main judgment criterion: rate
      of agreement between doctor diagnosis (is this patient dependent?), and patient
      evaluation (dependence is positive if at least 3 of the DSM-IV items are met).
      Results. One hundred and twenty-eight patients were included by 11 doctors: 89
      (69.5%) cases of agreement between doctor diagnosis and patient self evaluation
      and 39 (30.5%) cases of disagreement Discussion. There is an over assessment of
      dependence: doctors diagnose a dependence in 72% of the disagreement cases
      although there is none according to the self evaluation; the over assessment
      shows how difficult it is to evaluate dependence in general practice medicine.

PMID- 22850106
TI  - Reversal of vanadium-induced toxicity by combination therapy of tiferron and
      alpha-tocopherol in rat during pregnancy and their fetuses.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of tiferron (sodium 4,
      5-dihydroxybenzene-1, 3-disulfonate) per se and combination with alpha-tocopherol
      against vanadium induced developmental toxicity. Vanadium, as vanadyl sulphate
      pentahydrate, was evaluated for embryotoxic/fetotoxic effect in female albino
      rats (Sprague Dawley). METHODS: The compound was administered by gavage to
      pregnant animals at a dose of 15 mg/kg/day, p.o. on day 6-15 of pregnancy
      (organogenesis). Tiferron was given on day 16-18 as chelating agent. Cesarean
      sections were performed on day 19 of gestation. RESULTS: Maternal toxicity was
      observed, the level of sugar in the blood decreased, while we observed an
      increase in serum protein, serum alkaline phosphatase and serum transaminase
      activity. Level of lipid peroxidation showed enhances value in fetal and maternal
      liver. Vanadium induced inhibition in glycogen contents. Protein contents were
      decreased in vital organs where as increased in uterus and placenta. There was
      increased activity of acid phosphatase with the concomitant decline in alkaline
      phosphatase, adenosine triphosphatase and succnic dehydrogenase after vanadium
      intoxication. Toxicant caused severe alteration in histopathological observation
      of maternal and fetal liver, kidney, uterus and placenta proving its toxic
      consequences at cellular level. Tiferron along with alpha-tocopherol dramatically
      reversed alterations of all variables towards control rather than individual
      treatment. CONCLUSION: The combination therapy of tiferron and alpha-tocopherol
      played a beneficial role in reducing vanadium induced developmental toxicity.

PMID- 22850107
TI  - [Severe meprobamate poisoning: description of 146 cases in a French department].
AB  - Meprobamate poisoning are serious and sometimes fatal. Faced with a potential
      stop of marketing, we conducted a multicenter retrospective study to assess the
      severity criteria presented by patients admitted to the ICU for severe
      meprobamate poisoning, whether with alone form or in combination with
      aceprometazine. One hundred fourty-six patients have been enrolled between
      January 2005 and June 2011: 38 had a single meprobamate poisoning, 104 to
      meprobamate and aceprometazine and 4 to both forms. At admission, 88% of patients
      exhibited coma (Glasgow <= 7) and half of them a systolic blood pressure <= 90
      mmHg. Mortality rate was 3%. Our results did not find any significant between
      group difference, either in regard of clinical or biological severity criteria.
      These data argue for a cessation of marketing of all meprobamate-based
      specialities.

PMID- 22850110
TI  - Clinical and radiological features of Mycobacterium kansasii and other NTM
      infections.
AB  - BACKGROUND: Mycobacterium kansasii infection is one of the most common causes of
      nontuberculous mycobacterial lung disease in the world. However, it is not
      possible to differentiate completely between M. kansasii and other nontuberculous
      mycobacteria (NTM) because of a lack of direct comparative studies. This
      retrospective study sought to identify their clinical and radiological features
      systematically. METHODS: The sample included 98 consecutive patients with a
      culture-positive diagnosis of NTM infection, derived from the databases of the
      Laboratory of Microbiology of a tertiary medical center and two outpatient
      tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients
      fulfilled disease criteria for treatment. Data on patient background and clinical
      features were collected, and chest radiographs were evaluated. RESULTS: In the M.
      kansasii group, n = 27 (42%) were native-born Israelis compared to 9.4% (n = 3)
      of all other NTM groups (p = 0.0001). Similar rates of co-morbid diseases,
      including diabetes mellitus, heart disease, lung diseases, and malignancy were
      noted in both groups. Old TB was less common in the M. kansasii group compared to
      the other NTM (3.1% vs. 23.5%, p = 0.003). Clinical symptoms were significantly
      more common in patients with M. kansasii infection. On radiological study, M.
      kansasii infection was associated with more cavitations and unilaterality.
      Patients with M. kansasii infection had a higher likelihood of right upper lobe
      disease (p = 0.001). Pleural effusions and lymphadenopathy were found only in a
      few patients in each group. CONCLUSION: Major differences in the epidemiologic
      and clinical features of M. kansasii infection and other NTM have important
      diagnostic and clinical implications.

PMID- 22850108
TI  - [Hypomagnesaemia and hypocalcemia-induced by omeprazole].

PMID- 22850112
TI  - GLTSCR2 contributes to the death resistance and invasiveness of hypoxia-selected
      cancer cells.
AB  - Tumor hypoxia may be an indicator of poor survival in cancer patients. Thus, an
      understanding of the molecular mechanism responsible for hypoxic tumor selection
      is essential to gain further insight into tumor biology. Our aim in this study
      was to investigate whether hypoxia-responsive GLTSCR2 contributes to death
      resistance and increased invasiveness of hypoxia-selected glioblastoma cells. We
      found that repeated hypoxia downregulates p53-upstream regulator, GLTSCR2, which
      resulted in increased death resistance and invasive potential of glioblastoma
      cells. Restoration of GLTSCR2 expression suppressed the malignant potential of
      hypoxia-selected cells. Our results indicate that GLTSCR2 participates in hypoxia
      induced malignant potential.

PMID- 22850114
TI  - A687V EZH2 is a gain-of-function mutation found in lymphoma patients.
AB  - Heterozygous point mutations at Y641 and A677 in the EZH2 SET domain are
      prevalent in about 10-24% of Non-Hodgkin lymphomas (NHL). Previous studies
      indicate that these are gain-of-function mutations leading to the
      hypertrimethylation of H3K27. These EZH2 mutations may drive the proliferation of
      lymphoma and make EZH2 a molecular target for patients harboring these mutations.
      Here, another EZH2 SET domain point mutation, A687V, occurring in about 1-2% of
      lymphoma patients, is also shown to be a gain-of-function mutation that greatly
      enhances its ability to perform dimethylation relative to wild-type EZH2 and is
      equally proficient at catalyzing trimethylation. We propose that A687V EZH2 also
      leads to hypertrimethylation of H3K27 and may thus be a driver mutation in NHL.

PMID- 22850113
TI  - A reporter system that discriminates EF-hand-sensor motifs from signal-modulators
      at the single-motif level.
AB  - The T-protein is a single-polypeptide bi-functional enzyme composed of a
      chorismate mutase domain fused to a prephenate dehydrogenase domain (TyrA). We
      replaced the chorismate mutase domain with canonical or pseudo-Ca(2+)-binding
      motifs (EF-hand). Canonical-EF-hand-motifs differentiate from pseudo-EF-hand
      motifs by experimenting a Ca(2+)-dependent conformational change. The Ca(2+)-free
      EF-hand-TyrA fusion-proteins showed TyrA activity at the T-protein level.
      Canonical-EF-hand-TyrA fusions showed a Ca(2+)-dependent loss of TyrA activity,
      but a pseudo-EF-hand-TyrA fusion showed high TyrA activity level in excess-Ca(2+)
      conditions. Because TyrA activity exhibits robust changes in response to Ca(2+)
      dependent-EF-hand conformational alterations, TyrA could be a good Ca(2+)
      reporter enzyme. A chimeric canonical/pseudo-EF-hand strategy is proposed to
      confer pseudo-EF-hand motifs with a Ca(2+)-dependent conformational change.

PMID- 22850115
TI  - Sequence-function-stability relationships in proteins from datasets of
      functionally annotated variants: the case of TEM beta-lactamases.
AB  - A dataset of TEM lactamase variants with different substrate and inhibition
      profiles was compiled and analyzed. Trends show that loops are the main evolvable
      regions in these enzymes, gradually accumulating mutations to generate
      increasingly complex functions. Notably, many mutations present in evolved
      enzymes are also found in simpler variants, probably originating functional
      promiscuity. Following a function-stability tradeoff, the increase in functional
      complexity driven by accumulation of mutations fosters the incorporation of other
      stability-restoring substitutions, although our analysis suggests they might not
      be as "global" as generally accepted and seem instead specific to different
      networks of protein sites. Finally, we show how this dataset can be used to model
      functional changes in TEMs based on the physicochemical properties of the amino
      acids.

PMID- 22850116
TI  - Dual apoptotic DNA fragmentation system in the fly: Drep2 is a novel nuclease of
      which activity is inhibited by Drep3.
AB  - DNA fragmentation is the hallmark of apoptotic cells and mainly mediated by the
      DNA fragmentation factor DFF40(CAD)/DFF45(ICAD). DFF40 is a novel nuclease,
      whereas DFF45 is an inhibitor that can suppress the nuclease activity. Apoptotic
      DNA fragmentation in the fly is controlled by four DFF-related proteins, known as
      Drep1, 2, 3 and 4. However, the functions of Drep2 and Drep3 are totally unknown.
      Here, we found that Drep2 is a novel nuclease whose activity is inhibited by
      Drep3 through a tight interaction with the CIDE domain. Our results suggest that
      the fly has dual apoptotic DNA fragmentation systems: Drep1: Drep4 and Drep2:
      Drep3 complexes.

PMID- 22850117
TI  - Detection of rare reassortant G5P[6] rotavirus, Bulgaria.
AB  - During the ongoing rotavirus strain surveillance program conducted in Bulgaria,
      an unusual human rotavirus A (RVA) strain, RVA/Human/BG/BG620/2008/G5P[6], was
      identified among 2200 genotyped Bulgarian RVAs. This strain showed the following
      genomic configuration: G5-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analysis
      of the genes encoding the neutralization proteins and backbone genes identified a
      probable mixture of RVA genes of human and porcine origin. The VP1, VP6 and NSP2
      genes were more closely related to typical human rotavirus strains. The remaining
      eight genes were either closely related to typical porcine and unusual human
      porcine reassortant rotavirus strains or were equally distant from reference
      human and porcine strains. This study is the first to report an unusual rotavirus
      isolate with G5P[6] genotype in Europe which has most likely emerged from
      zoonotic transmission. The absence of porcine rotavirus sequence data from this
      area did not permit to assess if the suspected ancestral zoonotic porcine strain
      already had human rotavirus genes in its genome when transmitted from pig to
      human, or, the transmission was coupled or followed by gene reassortment
      event(s). Because our strain shared no neutralization antigens with rotavirus
      vaccines used for routine immunization in children, attention is needed to
      monitor if this G-P combination will be able to emerge in human populations. A
      better understanding of the ecology of rotavirus zoonoses requires simultaneous
      monitoring of rotavirus strains in humans and animals.

PMID- 22850118
TI  - The implementation and effectiveness of school-based nutrition promotion
      programmes using a health-promoting schools approach: a systematic review.
AB  - OBJECTIVE: To evaluate implementation and effectiveness of nutrition promotion
      programmes using the health-promoting schools (HPS) approach, to indicate areas
      where further research is needed and to make recommendations for practice in this
      field. DESIGN: The searched electronic databases included: CINAHL, Cochrane
      Library, Health Reference Center, Informit Search, MEDLINE, ProQuest, PsycINFO,
      PubMed, ScienceDirect, Scopus, Social Services Abstracts and Web of Science.
      Inclusion criteria were: (i) controlled or before-and-after studies evaluating a
      nutrition intervention and involving the HPS approach, either fully or in part;
      (ii) provision of information about components and delivery of the intervention;
      and (iii) report on all evaluated outcomes. SETTING: Schools. SUBJECTS: Students,
      parents and school staff. RESULTS: All included studies described intervention
      delivery and six reported on process evaluation. In intervention schools school
      environment and ethos were more supportive, appropriate curriculum was delivered
      and parents and/or the community were more engaged and involved. Students
      participated in interventions at differing levels, but the majority was satisfied
      with the intervention. The evidence indicates that nutrition promotion programmes
      using the HPS approach can increase participants' consumption of high-fibre
      foods, healthier snacks, water, milk, fruit and vegetables. It can also reduce
      participants' 'breakfast skipping', as well as reduce intakes of red food, low
      nutrient dense foods, fatty and cream foods, sweet drinks consumption and eating
      disorders. It can help to develop hygienic habits and improved food safety
      behaviours. CONCLUSIONS: More professional training for teachers in the HPS
      approach, further qualitative studies, longer intervention periods, improved
      follow-up evaluations and adequate funding are required for future school-based
      nutrition promotion programmes.

PMID- 22850120
TI  - Effectiveness of 1 dose of influenza A (H1N1) 2009 monovalent vaccines in
      preventing reverse-transcription polymerase chain reaction-confirmed H1N1
      infection among school-aged children in maine.
AB  - BACKGROUND: In late October 2009, school-located pandemic vaccination was
      initiated in Maine before or concurrent with 2009 pandemic influenza A (H1N1)
      virus (pH1N1) peak activity. METHODS: A case-control evaluation of 2009 H1N1
      vaccine effectiveness was conducted in schools in Cumberland County, Maine. A
      case was a child who had an acute respiratory illness during 2 November-18
      December 2009, and who tested positive for pH1N1 by real-time reverse
      transcription polymerase chain reaction (rRT-PCR). For each case, >= 4 event time
      matched controls were sampled among classmates present in school during the study
      period who did not have an influenza-like illness. Vaccine effectiveness was
      calculated as (1 - adjusted odds ratio [aOR])100%; aOR was estimated by using
      weighted logistic regression. RESULTS: After adjusting for a diagnosis of asthma,
      1 dose of 2009 H1N1 vaccine provided 69% protection (95% confidence interval
      (CI), 13-89) against rRT-PCR-confirmed H1N1 infection. Vaccine effectiveness
      estimates for live attenuated and inactivated vaccine were 81% (95% CI, -37 to
      97), and 58% (95% CI: -39 to 87), respectively. CONCLUSIONS: One dose of
      monovalent pandemic vaccine provided substantial protection against pH1N1
      infection among school-aged children.

PMID- 22850122
TI  - Clinical progress and risk factors for death in severe fever with
      thrombocytopenia syndrome patients.
AB  - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging
      infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate
      of 12%. The clinical factors for death in SFTS patients remain unclear. METHODS:
      Clinical features and laboratory parameters were dynamically collected for 11
      fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to
      evaluate the risk factors associated with death. RESULTS: Dynamic tracking of
      laboratory parameters revealed that during the initial fever stage, the viral
      load was comparable for the patients who survived as well as the ones that died.
      Then in the second stage when multi-organ dysfunction occurred, from 7-13 days
      after disease onset, the viral load decreased in survivors but it remained high
      in the patients that died. The key risk factors that contributed to patient death
      were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine
      kinase, and creatine kinase fraction, as well as the appearance of CNS (central
      nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular
      coagulation, and multi-organ failure. All clinical markers reverted to normal in
      the convalescent stage for SFTS patients who survived. CONCLUSIONS: We identified
      a period of 7-13 days after the onset of illness as the critical stage in SFTS
      progression. A sustained serum viral load may indicate that disease conditions
      will worsen and lead to death.

PMID- 22850119
TI  - Prevalence of and risk factors for anal human papillomavirus infection among
      young healthy women in Costa Rica.
AB  - BACKGROUND: Anal cancer is caused by human papillomavirus (HPV), yet little is
      known about anal HPV infection among healthy young women. METHODS: A total of
      2017 sexually active women in the control arm of an HPV-16/18 vaccine trial had a
      single anal specimen collected by a clinician at the 4-year study visit. Samples
      were tested for HPV by SPF(10) PCR/DEIA/LiPA(25), version 1. RESULTS: A total of
      4% of women had HPV-16, 22% had oncogenic HPV, and 31% had any HPV detected in an
      anal specimen. The prevalence of anal HPV was higher among women who reported
      anal intercourse, compared with those who did not (43.4% vs 28.4%; P< .001).
      Among women who reported anal intercourse, cervical HPV (adjusted odds ratio
      [aOR], 5.3 [95% confidence interval {CI}, 3.4-8.2]), number of sex partners (aOR,
      2.2 [95% CI, 1.1-4.6] for >= 4 partners), and number of anal intercourse partners
      (aOR, 1.9 [95% CI, 1.1-3.3] for >= 2 partners) were independent risk factors for
      anal HPV detection. Among women who reported no anal intercourse, cervical HPV
      (aOR, 4.7 [95% CI, 3.7-5.9]), number of sex partners (aOR, 2.4 [95% CI, 1.7-3.4]
      for >= 4 partners), and report of anal fissures (aOR, 2.3 [95% CI, 1.1-4.8]) were
      associated with an increased odds of anal HPV detection. CONCLUSION: Anal HPV is
      common among young women, even those who report no anal sex, and was associated
      with cervical HPV infection. Anal fissures in women who report never having had
      anal intercourse may facilitate HPV exposure. CLINICAL TRIALS REGISTRATION:
      NCT00128661.

PMID- 22850123
TI  - The food reaching test: a sensitive test of behavioral improvements by deep brain
      stimulation in MPTP-treated monkey.
AB  - We modified an objective behavioral test, namely the food reaching test (FRT),
      for quantitative assessment of motor performance improved by deep brain
      stimulation (DBS) of the subthalamic nucleus (STN) in the Parkinsonian monkeys.
      The symptomatic features and their severity in 3 monkeys treated with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated with a subjective monkey
      Parkinson's disease rating scale (PDRS). We then performed STN-DBS with the
      minimum current intensity that stopped the tremor. The time required for the
      monkeys to pick up all 5 pieces of potato (FRT time) was measured as a major
      index to evaluate bradykinesia. The success rate was adopted as another index for
      assessing overall motor impairments. Although both FRT time and PDRS score were
      similarly improved by STN-DBS, change of FRT time appeared more sensitive than
      that of PDRS scores. FRT is an easily trained behavioral test with high
      objectivity and sensitivity that can be applied for assessing motor performance
      in MPTP-treated monkeys during experiments in a restrained condition such as
      functional imaging of the brain.

PMID- 22850124
TI  - Quantitative analysis of rectal cancer by spectral domain optical coherence
      tomography.
AB  - To quantify OCT images of rectal tissue for clinic diagnosis, the scattering
      coefficient of the tissue is extracted by curve fitting the OCT signals to a
      confocal single model. A total of 1000 measurements (half and half of normal and
      malignant tissues) were obtained from 16 recta. The normal rectal tissue has a
      larger scattering coefficient ranging from 1.09 to 5.41 mm-1 with a mean value of
      2.29 mm-1 (std:+/-0.32), while the malignant group shows lower scattering
      property and the values ranging from 0.25 to 2.69 mm-1 with a mean value of 1.41
      mm-1 (std:+/-0.18). The peri-cancer of recta has also been investigated to
      distinguish the difference between normal and malignant rectal tissue. The
      results demonstrate that the quantitative analysis of the rectal tissue can be
      used as a promising diagnostic criterion of early rectal cancer, which has great
      value for clinical medical applications.

PMID- 22850126
TI  - Platelet count/spleen diameter ratio:  can it replace endoscopy for the screening
      of esophageal varices in cirrhotic patients?

PMID- 22850125
TI  - The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism
      in rodents possibly via inhibition of hypothalamic insulin signalling.
AB  - Secondary metabolites of herbs and spices are widely used as an alternative
      strategy in the therapy of various diseases. The polyphenols naringenin,
      quercetin and curcumin have been characterised as anti-diabetic agents.
      Conversely, in vitro, naringenin and quercetin are described to inhibit
      phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal
      control of whole body glucose homoeostasis. Using both in vitro and in vivo
      experiments, we tested whether the inhibitory effect on PI3K occurs in neurons
      and if it might affect whole body glucose homoeostasis. Quercetin was found to
      inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream
      target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In
      Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg
      administered orally) diminished insulin-induced phosphorylation of Akt (Ser473)
      in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In
      agreement with this finding, glucose tolerance in naringenin-treated hamsters
      (oral) and mice (oral and intracerebroventricular) was reduced compared with
      controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was
      ineffective. Circulating levels of insulin and insulin-like growth factor-binding
      protein were not affected by the polyphenols. Oral quercetin reduced the
      respiratory quotient, suggesting that glucose utilisation was impaired after
      treatment. These data demonstrate that low doses of naringenin and quercetin
      acutely and potently impair glucose homoeostasis. This effect may be mediated by
      inhibition of hypothalamic PI3K signalling. Whether chronic impairments in
      glucose homoeostasis occur after long-term application remains to be identified.

PMID- 22850121
TI  - Substitution of rifapentine for rifampin during intensive phase treatment of
      pulmonary tuberculosis: study 29 of the tuberculosis trials consortium.
AB  - BACKGROUND: Rifapentine administered 5 days per week has potent activity in mouse
      models of antituberculosis chemotherapy, but efficacy and safety data are limited
      in humans. We compared the antimicrobial activity and safety of rifapentine vs
      rifampin during the first 8 weeks of pulmonary tuberculosis treatment. METHODS:
      In total, 531 adults with sputum smear-positive pulmonary tuberculosis were
      randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5
      days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and
      ethambutol. Coprimary outcomes were negative sputum culture on liquid and on
      solid media at completion of intensive phase. RESULTS: Negative cultures on solid
      media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171
      of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95%
      confidence interval [CI]: -4.3, 10.5); negative cultures in liquid media occurred
      in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the
      rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4). Among 529 participants
      who received study therapy, 40 of 254 participants (15.7%) in the rifampin group
      and 40 of 275 participants (14.5%) in the rifapentine group prematurely
      discontinued treatment (P=.79). CONCLUSIONS: The rifapentine regimen was safe but
      not significantly more active than a standard rifampin regimen, by the surrogate
      endpoint of culture status at completion of intensive phase. Assessment of higher
      exposures to rifapentine for tuberculosis treatment is warranted. CLINICAL TRIALS
      REGISTRATION: NCT00694629.

PMID- 22850127
TI  - The genotype frequencies of IL28B polymorphisms (rs12979860, rs8099917) among
      Turkish patients with hepatitis C.

PMID- 22850128
TI  - Probiotics: should we be more definitive in terminology?

PMID- 22850130
TI  - Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl
      ester transfer protein in type 2 diabetes mellitus.
AB  - To address the effects of ezetimibe on high-density lipoprotein (HDL) metabolism,
      the HDL subclasses, cholesteryl ester transfer protein (CETP), and lecithin
      cholesterol acyltransferase (LCAT) were measured in patients with type 2 diabetes
      mellitus (T2DM).  Twenty-three hypercholesterolemic patients with T2DM were
      treated with 10 mg of ezetimibe daily for 12 weeks.  Plasma total cholesterol
      (TC), low-density lipoprotein (LDL)-cholesterol (C), HDL-C, HDL(2)-C, HDL(3)-C,
      CETP mass, and LCAT activity were measured.  HDL-C and HDL(2)-C increased by 5%
      (p<0.05) and 12% (p<0.01), respectively, in response to ezetimibe.  Of the 23
      patients, 21 had decreased CETP mass, which led to an average reduction of 20%
      (p<0.0001).  LCAT activity also decreased by 6% (p<0.01).  A significant positive
      correlation was found in the changes from baseline between HDL(2)-C and CETP
      mass, whereas a significant inverse relationship was observed between HDL(3)-C
      and CETP mass.  Furthermore, the change in HDL-C was positively correlated with
      the change in LCAT activity.  In conclusion, ezetimibe may affect HDL metabolism
      and reverse cholesterol transport, especially CETP, in T2DM.  These observations
      may provide some insights into how ezetimibe prevents atherosclerosis.

PMID- 22850132
TI  - A successful journey in occupational health nursing.

PMID- 22850131
TI  - Delay in the onset of puberty of intrauterine growth retarded female rats cannot
      be rescued with hypernutrition after birth.
AB  - Perinatal undernutrition is known to disturb reproductive development, in
      particular by delaying the onset of puberty in certain species.  Using a rat
      model, we studied whether hypernutrition after birth can rescue the delayed onset
      of puberty in intrauterine undernourished female rats.  Pregnant rats were
      divided into two groups: the maternal normal nutrition (mNN, n = 8) and maternal
      undernutrition (mUN, n = 9) groups.  In the mUN group, dams received 50% of the
      daily food intake of the mNN group from day 15 of pregnancy until delivery.  Pups
      from both the mNN and mUN dams were then separated into two groups, based on
      their postnatal feeding conditions: control-normal nutrition (control-NN),
      control-hypernutrition (control-HN), Intrauterine growth retardation (IUGR)
      normal nutrition (IUGR-NN), and IUGR-hypernutrition (IUGR-HN).  Litter sizes of
      the hypernutrition groups were controlled to five pups per dam, and normal
      nutrition groups to 12-13 pups per dam.  From postnatal day 30, pups were
      inspected daily for vaginal opening (VO).  The age of VO in the IUGR-NN group was
      35.7 +/- 2.4 days (mean +/- SD), which was significantly delayed compared to that
      of the control-NN group (33.8 +/- 0.8 days). The age of VO in the IUGR-HN group
      was 35.5 +/- 2.3 days, which was significantly delayed compared to that of the
      control-HN group (33.5 +/- 0.8 days).  Interestingly, the age of VO did not
      differ between the IUGR-NN and IUGR-HN groups.  In conclusion, maternal
      undernutrition delays puberty in female offspring, and this delay in puberty
      cannot be rescued with hypernutrition after birth.

PMID- 22850133
TI  - Scrubs and scuba gear--working on land and under the sea.
AB  - A nurse working at a remote island resort meets the diverse health and safety
      needs of employees and guests and combines her love of nursing with her love of
      scuba diving.

PMID- 22850134
TI  - Burnout among workers in a pediatric health care system.
AB  - Burnout among health care workers is recognized as an organizational risk
      contributing to absenteeism, presenteeism, excessive turnover, or illness, and
      may also manifest as decreased patient satisfaction. Pediatric health care may
      add stressors including worried parents of ill or dying children, child custody
      issues, child abuse, and workplace violence. The purpose of this study was to
      measure burnout among workers in a regional pediatric health care system and
      report whether burnout in a pediatric health care system is different from
      previously published data on human service workers. The Maslach Burnout Inventory
      Human Services Survey (MBI-HSS) and the Copenhagen Burnout Inventory (CBI) were
      used to measure burnout. Pediatric health care workers expressed significantly
      less burnout as compared to published MBI-HSS scores and client-related CBI
      scores. Personal burnout CBI scores were not different, but work-related CBI
      scores were significantly higher than normative scores.

PMID- 22850135
TI  - Musculoskeletal symptoms, work ability, and disability among nursing personnel.
AB  - Nursing personnel are at risk for developing musculoskeletal symptoms, which can
      result in persistent pain and inability to work. This study was designed to
      investigate the occurrence of musculoskeletal symptoms and their association with
      work role as well as to verify the relationship between pain intensity and
      disability among symptomatic individuals. Three hundred one nursing personnel, of
      whom 80.7% had musculoskeletal symptoms in at least one body part, participated
      in the study. The mean work ability score of symptomatic personnel was lower for
      physical demands. A significant difference between symptomatic and asymptomatic
      personnel was found for each demand measured by the Work Role Functioning
      Questionnaire, except social demand. Correlations were moderate but significant
      between pain intensity and disability. The results suggest that musculoskeletal
      symptoms interfere with work life.

PMID- 22850136
TI  - Building a health literate workplace.
AB  - Approximately 36% of America's adult population cannot perform daily activities
      that require basic reading, writing, and numeric skills. Individuals who are at
      risk for low health literacy have demographics and socioeconomic backgrounds
      similar to those of individuals considered vulnerable by the National
      Occupational Research Agenda (NORA). Improving health literacy is a public health
      priority. Occupational health nurses can play a major role in assisting employers
      to build a health literate organization while improving the health of their
      employees. This article discusses attributes of a health literate organization,
      including organizational commitment, infrastructure, policies and practices with
      a health literacy priority, and effective communication at all levels.

PMID- 22850138
TI  - Associations of dietary calcium intake and calcium supplementation with
      myocardial infarction, stroke, and overall cardiovascular mortality.
AB  - Calcium supplements have been associated with elevated risk of myocardial
      infarction, whereas dietary calcium intake has not.

PMID- 22850139
TI  - Perspectives on human microbiome research ethics.
AB  - Study of ethical, legal, and social implications (ELSI) of human microbiome
      research has been integral to the Human Microbiome Project (HMP). This study
      explores core ELSI issues that arose during the first phase of the HMP from the
      perspective of individuals involved in the research. We conducted semi-structured
      in-depth interviews with investigators and NIH employees ("investigators")
      involved in the HMP, and with individuals recruited to participate in the HMP
      Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report
      findings related to three major ELSI issues: informed consent, data sharing, and
      return of results. Our findings demonstrate that investigators and recruits were
      similarly sensitive to these issues yet generally comfortable with study design
      in light of current knowledge about the microbiome.

PMID- 22850140
TI  - Sham surgery trial controls: perspectives of patients and their relatives.
AB  - This study reports on qualitative research conducted in the UK with people with
      Parkinson's Disease and their relatives on the subject of "sham surgery." It
      explores attitudes toward sham surgery and reasoning about hypothetical
      participation in a sham-controlled trial. Results showed that attitudes toward
      sham surgery may not necessarily predict trial participation behavior. A small
      majority of interviewees deemed sham surgery ethically acceptable with certain
      provisos, but hypothetical participation was driven primarily by disease severity
      and a lack of standard treatment options, with a preference for receiving the
      real surgery over sham. Ethical implications for patient equipoise and the
      autonomy of patients' research participation decisions are discussed.

PMID- 22850141
TI  - Ethical issues in a stage 1 cognitive-behavioral therapy feasibility study and
      trial to reduce alcohol use among HIV-infected outpatients in western Kenya.
AB  - Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred
      the conduct of local behavioral therapy trials for these problems, but the
      ethical issues involved in these trials have not been fully examined. In this
      paper, we discuss ethical issues that emerged during the conduct of a behavioral
      intervention adaptation and trial using cognitive-behavioral therapy to reduce
      alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was
      performed within our multinational collaboration, the USAID-Academic Model
      Providing Access to Healthcare Partnership. We discuss relevant ethical
      considerations and how we addressed them.

PMID- 22850142
TI  - Human research ethics committees: examining their roles and practices.
AB  - Considerable time and resources are invested in the ethics review process. We
      present qualitative data on how human research ethics committee members and
      health researchers perceive the role and function of the committee. The findings
      are based on interviews with 34 Australian ethics committee members and 54 health
      researchers. Although all participants agreed that the primary role of the ethics
      committee was to protect participants, there was disagreement regarding the
      additional roles undertaken by committees. Of particular concern were the
      perceptions from some ethics committee members and researchers that ethics
      committees were working to protect the institution's interests, as well as being
      overprotective toward research participants. This has the potential to lead to
      poor relations and mistrust between ethics committees and researchers.

PMID- 22850143
TI  - Local IRBs vs. federal agencies: shifting dynamics, systems, and relationships.
AB  - How IRBs relate to federal agencies, and the implications of these relationships,
      have received little, if any, systematic study. I interviewed 46 IRB chairs,
      directors, administrators, and members, contacting the leadership of 60 U.S. IRBs
      (every fourth one in the list of the top 240 institutions by NIH funding),
      interviewing IRB leaders from 34 (response rate=55%). IRBs describe complex
      direct and indirect relationships with federal agencies that affect IRBs through
      audits, guidance documents, and other communications, and can generate problems
      and challenges. Researchers often blame IRBs for frustrations, but IRBs often
      serve as the "local face" of federal regulations and agencies and are "stuck in
      the middle." These data have critical implications for policy, practice, and
      research.

PMID- 22850144
TI  - Case-based ethics education: the impact of cause complexity and outcome
      favorability on ethicality.
AB  - Case-based learning has been used across multiple disciplines, including ethics
      education, as an effective instructional tool. However, the value of case-based
      learning in ethics education has varied widely regarding case quality. Case
      content may significantly impact the ability of case-based ethics education to
      promote knowledge acquisition and knowledge transfer to future situations
      requiring ethical decision-making. This study examined two critical areas of
      ethical case content--causes and outcomes. Complexity of described causes and
      outcome favorability were manipulated in two ethical cases used during an ethics
      education course. Results suggest that including information in case studies
      reflecting clear, simple key causes and negative outcomes results in better
      ethical sensemaking and ethical decision-making. Implications regarding case
      content and case-based ethics education are explored.

PMID- 22850145
TI  - Evaluation of the content and process of informed consent discussions for
      neonatal research.
AB  - Studies of informed consent for neonatal research suggest that there are gaps in
      parental understanding of key aspects of research. Few studies have examined
      parental understanding and investigator disclosure simultaneously. This pilot
      study evaluated the content and processes of 21 audio-recorded consent
      discussions with parents of eligible newborns, as well as parents' self-reported
      comprehension of research elements following these discussions. Gaps in both
      investigator disclosure and parental understanding were found. Nevertheless,
      parents reported comprehension of a greater number of research elements than were
      actually disclosed by investigators. Our preliminary results indicate the
      feasibility and potential utility of jointly examining parental understanding and
      investigator behavior to characterize consent for neonatal research. Directions
      for future research are suggested.

PMID- 22850146
TI  - Appealing to altruism is not enough: motivators for participating in health
      services research.
AB  - This pilot study sought to identify motivators and barriers to participating in a
      longitudinal survey; we interviewed patients and practitioners at a
      multidisciplinary primary care clinic where the proposed project would be based.
      While altruism motivates participation in medical research, we found that for
      many potential participants, the opportunity to benefit directly was the primary,
      and sometimes the only motive to participate or encourage participation in the
      research project. Patients often wanted direct feedback from their individual
      results, and they expected to provide consent before the results were forwarded
      to other parties such as their practitioners. Similarly, some practitioners were
      more likely to support the project if participation benefited patients directly.
      Other factors were also identified that influenced the acceptability and
      perceived risks and benefits of participating. More work is needed to understand
      these motivators and how patients might benefit directly from participating in
      health services research, especially when direct medical benefit is not possible.

PMID- 22850148
TI  - Educational advantage.
AB  - Emerging issues in human research challenge us to think outside of the box. The
      first three papers in this issue provide such challenges. New ethical issues
      arise in connection with research on the human microbiome, sham surgery, and the
      use of psychotherapy in research interventions in tribal cultures in Kenya.

PMID- 22850150
TI  - Noncompressible torso hemorrhage: a review with contemporary definitions and
      management strategies.
AB  - Trauma resulting in hemorrhage from vascular disruption within the torso is a
      challenging scenario, with a propensity to be lethal in the first hour following
      trauma. The term noncompressible torso hemorrhage (NCTH) was only recently coined
      as part of contemporary studies describing the epidemiology of wounding during
      the wars in Afghanistan and Iraq. This article provides a contemporary review of
      NCTH, including a unifying definition to promote future study as well as a
      description of resuscitative and operative management strategies to be used in
      this setting, and sets a course for research to improve mortality following this
      vexing injury pattern.

PMID- 22850149
TI  - Prehospital emergency trauma care and management.
AB  - Prehospital care of the trauma patient is continuing to evolve; however, the
      principles of airway maintenance, hemorrhage control, and appropriate
      resuscitative maneuvers remain central to the role of the emergency medical care
      provider. Recent changes in the regulations for research in emergency settings
      will allow randomized trials to proceed to test new devices, drugs, and
      resuscitative strategies in the prehospital environment. The creation of
      prehospital research networks will provide the appropriate infrastructure to
      greatly facilitate the development of new protocols and the execution of large
      scale randomized trials with the potential to change current prehospital
      practice.

PMID- 22850151
TI  - The evolution of damage control surgery.
AB  - The philosophy of damage control surgery has developed tremendously over the past
      10 years. It has expanded outside the original boundaries of the abdomen and has
      been applied to all aspects of trauma care, ranging from resuscitation to limb
      threatening vascular injuries. In recent years, the US military has taken the
      concept to a new level by initiating a damage control approach at the point of
      injury and continuing it through a transcontinental health care system. This
      article highlights many recent advances in damage control surgery and discusses
      proper patient selection and the risks associated with this management strategy.

PMID- 22850152
TI  - Towards hemostatic resuscitation: the changing understanding of acute traumatic
      biology, massive bleeding, and damage-control resuscitation.
AB  - During the past decade there has been a profound change in the understanding of
      postinjury coagulation. Concurrently, new data suggest that a resuscitative
      strategy to minimize large volumes of crystalloid while recreating whole is
      associated with reduced morbidity and mortality. This article outlines the
      history of resuscitation and transfusion practices in trauma, the changing
      understanding of coagulation and inflammation, and clinical data driving changes
      in resuscitative conduct. Finally, the current state of the science suggests
      future basic science and clinical investigation that will drive changes in
      transfusion and resuscitation in severely injured military personnel and civilian
      patients.

PMID- 22850153
TI  - Improving trauma care in the ICU: best practices, quality improvement
      initiatives, and organization.
AB  - Optimal care of critically ill trauma patients remains a challenge within modern
      medical systems. During the past decade, emerging technologies and organizational
      improvements have greatly advanced the care of these patients. The effective
      implementation of best practice initiatives has led to measurable improvement in
      outcomes while also reducing health care costs. Continued advances in the
      implementation of these initiatives and ICU organization are required, however,
      to insure that optimal care is provided to this unique patient population.

PMID- 22850154
TI  - Advanced technologies in trauma critical care management.
AB  - Care of critically injured patients has evolved over the 50 years since Shoemaker
      established one of the first trauma units at Cook County Hospital in 1962. Modern
      trauma intensive care units offer a high nurse-to-patient ratio, physicians and
      midlevel providers who manage the patients, and technologically advanced monitors
      and therapeutic devices designed to optimize the care of patients. This article
      describes advances that have transformed trauma critical care, including bedside
      ultrasonography, novel patient monitoring techniques, extracorporeal support, and
      negative pressure dressings. It also discusses how to evaluate the safety and
      efficacy of future advances in trauma critical care.

PMID- 22850155
TI  - Long-range critical care evacuation and reoperative surgery.
AB  - Long-range critical care aeromedical evacuation has significantly contributed to
      the unprecedented survival during recent military operations. With advances in
      critical care, patients with increased injury severity and overall complexity are
      routinely evacuated while resuscitation is ongoing. Additional specialty teams
      now provide advanced pulmonary rescue therapies for the most critically ill
      patients. As part of the continuum of trauma care, an overseas fixed facility
      provides follow-on emergency surgical critical care to optimize patient outcomes
      before final evacuation to the continental United States.

PMID- 22850156
TI  - Spectrum of traumatic brain injury from mild to severe.
AB  - Traumatic brain injury (TBI) involves significant damage of the brain parenchyma,
      and is the leading cause of morbidity and mortality after trauma. It is thus
      essential for all physicians involved in acute care medicine and surgery to have
      a thorough understanding of TBI. Management of the patient with TBI is a rapidly
      advancing field, characterized by an improved understanding of intracranial
      pathophysiology and decreasing overall mortality largely because of improved
      neurocritical and surgical care. This article summarizes the classification
      system, management approaches, and recent controversies in the care of mild,
      moderate, and severe TBI.

PMID- 22850157
TI  - Evolving changes in the management of burns and environmental injuries.
AB  - Burns and environmental injuries are common as primary or secondary problems in
      survivors of natural disasters, terrorist incidents, and combat operations. In
      recent years, intensive military medical experience has resulted in substantial
      progress in treatment of these important problems. This article reviews practical
      applications of this new knowledge.

PMID- 22850158
TI  - Management of complex extremity injuries: tourniquets, compartment syndrome
      detection, fasciotomy, and amputation care.
AB  - Historically, complex extremity injuries, otherwise known as mangled extremities,
      have been difficult management problems. This is especially true in multiply
      injured patients where many priorities exist and where amputation is considered a
      failure of limb salvage. Over the past decade, advances in the total management
      of complex extremity injuries, from the placement of life-saving and limb-saving
      tourniquets in the prehospital setting to the advancement of prosthetics and
      rehabilitation months to years later, have resulted in superb functional results
      regardless of whether limb salvage or amputation is undertaken.

PMID- 22850159
TI  - Verification and regionalization of trauma systems: the impact of these efforts
      on trauma care in the United States.
AB  - Efforts to develop trauma systems in the United States followed the publication
      of the landmark article, "Accidental Death and Disability: The Neglected Disease
      of Modern Society," by the National Academy of Sciences (1966) and have resulted
      in the implementation of a system of care for the seriously injured in most
      states and within the US military. In 2007, Hoyt and Coimbra published an article
      detailing the history, organization, and future directions of trauma systems
      within the United States. This article provides an update of the developments
      that have occurred in trauma systems in system verification and regionalization.

PMID- 22850160
TI  - Trauma system configurations in other countries: the Israeli model.
AB  - Israel is a small country with a unique trauma system that was developed from the
      experience gained in peace and in war. That trauma system was designed to fit the
      state's current health system, which is different from the European and American
      systems. This article describes the infrastructure of both prehospital and in
      hospital trauma management, as well as the main cornerstones of their
      development. The experience that was gained from multiple mass casualty incidents
      is discussed. The protocols of mass casualty management in the prehospital and in
      hospital setup are described.

PMID- 22850161
TI  - Research and analytics in combat trauma care: converting data and experience to
      practical guidelines.
AB  - Throughout history, wars have resulted in medical advancements, especially in
      trauma. Once clinical challenges are identified, they require documentation and
      analysis before changes to care are introduced. The wars in Afghanistan and Iraq
      led to the collection of clinically relevant data from the entire medical system
      into a formal trauma registry. Improvements in data collection and human research
      oversight have allowed more effective and efficient techniques to capture and
      analyze trauma data, which has enabled rapid development and dissemination of
      clinical practice guidelines in the midst of war. These data-driven experiences
      are influencing trauma practice patterns in the civilian community.

PMID- 22850162
TI  - Graduate medical education in trauma/critical care and acute care surgery:
      defining goals for a new workforce.
AB  - The increasing need for skilled emergency surgical providers, coupled with
      decreasing experience in emergency surgery among trainees, has led to significant
      shortages in the availability of such surgeons. In response to this crisis,
      surgical leaders have developed a comprehensive curriculum and a set of
      professional standards to guide the training of a new specialist: the acute care
      surgeon. This article reviews the development and goals for Fellowship training
      of this new specialty.

PMID- 22850163
TI  - Recent advances and future directions in trauma care.

PMID- 22850164
TI  - Recent advances and future directions in trauma care.

PMID- 22850165
TI  - Recent advances and future directions in trauma care.

PMID- 22850166
TI  - A qualitative study to identify reasons for discharges against medical advice in
      the cardiovascular setting.
AB  - BACKGROUND: Cardiovascular disease (CVD) is responsible for the largest number of
      discharges against medical advice (AMA). However, there is limited information
      regarding the reasons for discharges AMA in the CVD setting. OBJECTIVE: To
      identify reasons for discharges AMA among patients with CVD. DESIGN: Qualitative
      study using focus group interviews (FGIs). PARTICIPANTS: A convenience sample of
      patients with a CVD-related discharge diagnosis who left AMA and providers
      (physicians, nurses and social workers) whose patients have left AMA. PRIMARY AND
      SECONDARY OUTCOMES: To identify patients' reasons for discharges AMA as
      identified by patients and providers. To identify strategies to reduce discharges
      AMA. APPROACH: FGIs were grouped according to patients, physicians and
      nurses/social workers. A content analysis was performed independently by three
      coauthors to identify the nature and range of the participants' viewpoints on the
      reasons for discharges AMA. The content analysis involved specific categories of
      reasons as motivated by the Health Belief Model as well as reasons (ie, themes)
      that emerged from the interview data. RESULTS: 9 patients, 10 physicians and 23
      nurses/social workers were recruited for the FGIs. Patients and providers
      reported the same three reasons for discharges AMA: (1) patient's preference for
      their own doctor, (2) long wait time and (3) factors outside the hospital.
      Patients identified an unmet expectation to be involved in setting the treatment
      plan as a reason to leave AMA. Participants identified improved communication as
      a solution for reducing discharges AMA. CONCLUSIONS: Patients wanted more
      involvement in their care, exhibited a strong preference for their own primary
      physician, felt that they spent a long time waiting in the hospital and were
      motivated to leave AMA by factors outside the hospital. Providers identified
      similar reasons except the patients' desire for involvement. Additional research
      is needed to determine the applicability of results in broader patient and
      provider populations.

PMID- 22850167
TI  - Prevalence of anal incontinence among Norwegian women: a cross-sectional study.
AB  - OBJECTIVE: Anal incontinence (AI) is a symptom associated with age, bowel
      symptoms and obstetric injuries. Primary aim of the study was to establish the
      prevalence of AI among women and secondarily to evaluate the impact on daily life
      and conditions associated with AI. DESIGN: A cross-sectional study. SETTING:
      Participants attended research stations located in different parts of Nord
      Trondelag county, Norway. Data were collected through interviews, questionnaires
      and clinical examinations. PARTICIPANTS: In total, 40 955 community-dwelling
      women aged 30 years and older were invited. A total of 25 037 women participated,
      giving a participation rate of 61.1%. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Fecal incontinence and flatal incontinence was defined as involuntary loss of
      feces and flatus weekly or more, respectively. AI was defined as the involuntary
      loss of feces and/or flatus weekly or more. Urgency was defined as the inability
      to defer defecation for 15 min. Statistical methods included prevalence estimates
      and logistic regression analysis. RESULTS: Questions about AI were completed by
      20 391 (82.4%) women. Among the 20 391 women, AI was reported by 19.1% (95% CI
      18.6% to 19.7%) and fecal incontinence was reported by 3.0% (95% CI 2.8% to
      3.2%). Urgency was experienced by 2586 women (12.7%, 95% CI 12.2 to 13.1). Impact
      on daily life was stated by 794 (26.0%, 95% CI 24.4 to 27.5) women with AI. In
      bivariate age-adjusted analysis of AI, OR and CI for urgency (OR 3.19, 95% CI
      2.92 to 3.49) and diarrhoea (OR 3.81, 95% CI 3.32 to 4.38) revealed strongest
      associations with AI. CONCLUSIONS: AI affects one in five women older than 30
      years. Strongest associated symptoms are urgency and diarrhoea. TRIAL
      REGISTRATION NUMBER: The study was approved by the Regional Committee for Medical
      and Health Research Ethics (No. 2009/1214) and followed the Declaration of
      Helsinki.

PMID- 22850168
TI  - Relationship between anatomical and functional assessments of coronary artery
      stenosis.

PMID- 22850169
TI  - Methane production from glycolate excreting algae as a new concept in the
      production of biofuels.
AB  - It is the aim of the present work to introduce a new concept for methane
      production by the interaction of a glycolate-excreting alga (Chlamydomonas
      reinhardtii) and methanogenic microbes operating in separate compartments within
      one photobioreactor. This approach requires a minimum number of metabolic steps
      to convert light energy to methane thereby reducing the energetic and financial
      costs of biomass formation, harvest and refinement. In this feasibility study it
      is shown that the physiological limitations for sustained glycolate production
      can be circumvented by the use of C. reinhardtii mutants whose carbon
      concentrating mechanisms or glycolate dehydrogenase are suppressed. The results
      also demonstrate that methanogenic microbes are able to thrive on glycolate as
      single carbon source for a long time period, delivering biogas composed of
      CO(2)/methane with only very minor contamination.

PMID- 22850170
TI  - Static respiration indices to investigate compost stability: effect of sample
      weight and temperature and comparison with dynamic respiration indices.
AB  - Goal of this work was to study the effect of sample weight and temperature on the
      microbial respiration indices of a static microbial respiration test used to
      quantify compost stability. The static respiration tests (SRT) were performed at
      two different temperatures (20 degrees C and 35 degrees C) using five different
      sample weights (19, 38, 56, 75 and 94 dry g). Results showed that at 35 degrees
      C, as sample weight increased, the magnitude of the respiration indices reduced.
      In addition, the 35 degrees C temperature resulted in higher static respiration
      activity indices compared to that at the 20 degrees C for two sample weights. The
      static respiration tests led to 2-2.5 times lower oxygen-related indices compared
      to those calculated in dynamic respiration tests (DRT); the 7-day CO(2)
      cumulative generations were, however, almost similar for both types of tests.
      Respiratory quotients (RQs) were constantly between 0.8 to 1.2 during the SRT.

PMID- 22850171
TI  - Waste activated sludge hydrolysis during ultrasonication: two-step
      disintegration.
AB  - In order to clearly describe the hydrolysis of waste activated sludge (WAS)
      during ultrasonication by a 2-step disintegration process, concentrations of
      ribonucleic acid (RNA) and bound extracellular polymeric substance (EPS) were
      measured. Apparently, different decreasing patterns of RNA and EPS concentrations
      during WAS hydrolysis made it possible to distinguish the floc disintegration
      (FD) and cell lysis (CL). Initially, FD and CL appear to take simultaneously, but
      the dominant hydrolytic process is shifted from FD to CL after 10 min of
      ultrasonication. Additional kinetic analysis of WAS hydrolysis was also
      conducted. A five-fold greater hydrolysis rate constant of FD relative to that of
      CL was observed, reflecting the different strengths of floc and cells. Therefore,
      different rates of increased solubilization during WAS hydrolysis appear to
      account for the initial disintegration of the rather loose part (sludge floc) and
      the subsequent disintegration of the rigid part (microbial cells).

PMID- 22850172
TI  - Nickel ion removal from wastewater using the microbial electrolysis cell.
AB  - In this study, the microbial electrolysis cell (MEC) was examined for treatment
      of wastewater containing nickel ion (Ni(2+)). Effects of initial Ni(2+)
      concentrations in catholyte, pH values of catholyte, and applied voltages on MEC
      performance were determined. Results showed that the Ni(2+) removal efficiency
      with the MEC was three times higher than those with an electrolysis cell and a
      microbial fuel cell. Ni(2+) removal efficiencies decreased from 99 +/- 0.6% to 33
      +/- 4.2% with the initial Ni(2+) concentrations from 50 to 1000 mg/L, while the
      mass removal of Ni(2+) increased consistently with the initial concentrations.
      Ni(2+) removal efficiencies in the MEC increased from 51 +/- 4.6% to 67 +/- 5.3%
      with the applied voltages from 0.5 to 1.1 V. These results demonstrate that the
      MEC can be an alternative process to effectively remove Ni(2+) from wastewater.

PMID- 22850173
TI  - Co-fermentation of water hyacinth and beverage wastewater in powder and pellet
      form for hydrogen production.
AB  - Hydrogen (H2) production potential of water hyacinth (WH) and beverage wastewater
      (BW) mixture in powder and pellet form at various combination ratios were
      evaluated. Batch co-fermentation results showed peak biogas production of 105.5
      mL and H2 production of 55.6 mL at the combination ratio of 1.6 g WH and 2.4 g BW
      in pellet form. With the same ratio in pellet form, the maximum H2 production
      rate 542 mL H2/L-d, maximum specific H2 production rate 869 mL H2/g VSS-d and H2
      yield 13.65 mL/g feedstock were obtained, and were 88, 88 and 34% higher than its
      powder form. The predominant soluble metabolite was acetate in the concentration
      of 1059-2639 mg COD/L (40-79% of total metabolites) in most runs during co
      fermentation of mixed feedstock. Carbon-to-nitrogen ratio and the physical form
      of the combined feedstock are essential criteria for optimum H2 production. Co
      fermentation also alleviates the waste disposal problem of the industries.

PMID- 22850174
TI  - Production of biodiesel from plant oil hydrolysates using an Aspergillus oryzae
      whole-cell biocatalyst highly expressing Candida antarctica lipase B.
AB  - For enzymatic biodiesel production from plant oil hydrolysates, an Aspergillus
      oryzae whole-cell biocatalyst that expresses Candida antarctica lipase B (r-CALB)
      with high esterification activity was developed. Each of soybean and palm oils
      was hydrolyzed using Candida rugosa lipase, and the resultant hydrolysates were
      subjected to esterification where immobilized r-CALB was used as a catalyst. In
      esterification, r-CALB afforded a methyl ester content of more than 90% after 6 h
      with the addition of 1.5 M equivalents of methanol. Favorably, stepwise additions
      of methanol and a little water were unnecessary for maintaining the lipase
      stability of r-CALB during esterification. During long-term esterification in a
      rotator, r-CALB can be recycled for 20 cycles without a significant loss of
      lipase activity, resulting in a methyl ester content of more than 90% even after
      the 20th batch. Therefore, the presented reaction system using r-CALB shows
      promise for biodiesel production from plant oil hydrolysates.

PMID- 22850175
TI  - Low melting point pyridinium ionic liquid pretreatment for enhancing enzymatic
      saccharification of cellulosic biomass.
AB  - The potential of 1-hexylpyridinium chloride ([Hpy][Cl]), to pretreat cellulosic
      feedstocks was investigated using microcrystalline cellulose (Avicel) and Bagasse
      at 80  degrees C or 100  degrees C. Short [Hpy][Cl] pretreatments, <30 min, at
      lower temperature accelerate subsequent enzymatic saccharification of Avicel.
      Over 95% conversion of pretreated Avicel to glucose was attained after 24h
      enzymatic saccharification under optimal conditions, whereas regenerated Bagasse
      showed 1-3-fold higher conversion than untreated biomass. FT-IR analysis of both
      Avicel and Bagasse samples pretreated with [Hpy][Cl] or 1-ethyl-3
      methyimidazolium acetate ([Emim][OAc]) revealed that these ionic liquids behaved
      differently during pretreatment. [Hpy][Cl] pretreatment for an extended duration
      (180 min) released mono- and disaccharides without using cellulase enzymes,
      suggesting [Hpy][Cl] has capability for direct saccharification of cellulosic
      feedstocks. On the basis of the results obtained, [Hpy][Cl] pretreatment enhanced
      initial reaction rates in enzymatic saccharification by either crystalline
      polymorphic alteration of cellulose or partial degradation of the crystalline
      cellulosic fraction in biomass.

PMID- 22850176
TI  - Elementary sulfur in effluent from denitrifying sulfide removal process as
      adsorbent for zinc(II).
AB  - The denitrifying sulfide removal (DSR) process can simultaneously convert
      sulfide, nitrate and organic compounds into elementary sulfur (S(0)), di-nitrogen
      gas and carbon dioxide, respectively. However, the S(0) formed in the DSR process
      are micro-sized colloids with negatively charged surface, making isolation of
      S(0) colloids from other biological cells and metabolites difficult. This study
      proposed the use of S(0) in DSR effluent as a novel adsorbent for zinc removal
      from wastewaters. Batch and continuous tests were conducted for efficient zinc
      removal with S(0)-containing DSR effluent. At pH<7.5, removal rates of zinc(II)
      were increased with increasing pH. The formed S(0) colloids carried negative
      charge onto which zinc(II) ions could be adsorbed via electrostatic interactions.
      The zinc(II) adsorbed S(0) colloids further enhanced coagulation-sedimentation
      efficiency of suspended solids in DSR effluents. The DSR effluent presents a
      promising coagulant for zinc(II) containing wastewaters.

PMID- 22850177
TI  - New insights into gill ionocyte and ion transporter function in euryhaline and
      diadromous fish.
AB  - Teleost fishes are able to acclimatize to seawater by secreting excess NaCl by
      means of specialized "ionocytes" in the gill epithelium. Antibodies against
      Na(+)/K(+)-ATPase (NKA) have been used since 1996 as a marker for identifying
      branchial ionocytes. Immunohistochemistry of NKA by itself and in combination
      with Na(+)/K(+)/2Cl(-) cotransporter and CFTR Cl(-) channel provided convincing
      evidence that ionocytes are functional during seawater acclimation, and also
      revealed morphological variations in ionocytes among teleost species. Recent
      development of antibodies to freshwater- and seawater-specific isoforms of the
      NKA alpha-subunit has allowed functional distinction of ion absorptive and
      secretory ionocytes in Atlantic salmon. Cutaneous ionocytes of tilapia embryos
      serve as a model for branchial ionocytes, allowing identification of 4 types: two
      involved in ion uptake, one responsible for salt secretion and one with unknown
      function. Combining molecular genetics, advanced imaging techniques and
      immunohistochemistry will rapidly advance our understanding of both the unity and
      diversity of ionocyte function and regulation in fish osmoregulation.

PMID- 22850178
TI  - Risk factors for otolaryngological foreign bodies in Eastern Poland.
AB  - OBJECTIVE: To identify the sociodemographic characteristics and risk factors
      associated with suspected foreign bodies in the ear, nose, throat, airway, and
      esophagus among Polish children. STUDY DESIGN: Case series with chart review.
      Setting Tertiary care medical center. SUBJECTS AND METHODS: A retrospective
      analysis of the medical records of patients hospitalized for a suspected foreign
      body (FB) between 1998 and 2008 was conducted. Data regarding place of residence,
      presence of siblings, parents' educational status, seasonality, psychomotor
      development, age, and sex were collected and statistically analyzed. RESULTS: Of
      the 1011 patients with suspected foreign body insertion, 849 (84%) had a positive
      diagnosis. Of the confirmed foreign bodies, 96 were found in the tracheobronchial
      tree, 142 were found in the esophagus, and 611 were located in the external
      auditory canals, nasopharyngeal passage, tonsils, auricles, or lips.
      Sociodemographically, 596 of the children came from urban areas, with a
      preponderance of males (55%). Objects were removed more frequently in summer and
      autumn (60%). Children with siblings (53%) predominated. The majority of patients
      (52%) had parents with an elementary education. Food was the most frequent
      foreign body in children under 3 years of age. Patients with delayed psychomotor
      development constituted 1.6% of the analyzed population. CONCLUSIONS: Being male,
      1 to 3 years of age, belonging to an urban family with siblings, and having
      parents with an elementary education increased the risk of foreign body
      insertion. Training caregivers about proper nutrition and safety rules when
      playing with children can reduce the risk of accidents related to foreign body
      insertion.

PMID- 22850179
TI  - The digital divide in Internet-based patient education materials.
AB  - The ubiquity of the Internet has led to the widespread availability of health
      related information to the public, and the subsequent empowerment of patients has
      fundamentally altered the patient-physician relationship. Among several concerns
      of physicians is the possibility that patients may be misinformed by information
      obtained from the Internet. One opportunity for health care providers to address
      this problem exists within Internet-based patient education materials (IPEMs).
      According to recent research in Otolaryngology-Head and Neck Surgery, IPEMs found
      within professional otolaryngology websites are written at the 8th- to 18th-grade
      reading comprehension level, essentially unchanged over the past 3 years. This
      greatly exceeds the fourth- to sixth-grade reading level recommended by the
      National Institutes of Health. Benefits, strategies, and challenges to improving
      the readability of IPEMs are discussed.

PMID- 22850180
TI  - T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make
      different contributions to colitis in mice.
AB  - BACKGROUND & AIMS: T helper (Th) 17 cells that express the retinoid-related
      orphan receptor (ROR) gammat contribute to the development of colitis in mice,
      yet are found in normal and inflamed intestine. We investigated their development
      and functions in intestines of mice. METHODS: We analyzed intestinal Th17 cells
      in healthy and inflamed intestinal tissues of mice. We analyzed expression of
      lymphotoxin (LT)alpha by Th17 cells and lymphoid tissue inducer-like cells.
      RESULTS: LTalpha(-/-) and RORgammat(-/-) mice had significantly lower percentages
      of naturally occurring Th17 cells in the small intestine than wild-type mice.
      Numbers of CD3(-)CD4(+/-)interleukin-7Ralpha(+)c-kit(+)CCR6(+)NKp46(-) lymphoid
      tissue inducer-like cells that produce interleukin-17A were increased in LTalpha(
      /-) and LTalpha(-/-) * recombination activating gene (RAG)-2(-/-) mice, compared
      with wild-type mice, but were absent from RORgammat(-/-) mice. Parabiosis of wild
      type and LTalpha(-/-) mice and bone marrow transplant experiments revealed that
      LTalpha-dependent gut-associated lymphoid tissue structures are required for
      generation of naturally occurring Th17 cells. However, when wild-type or LTalpha(
      /-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTalpha(-/-)*RAG
      2(-/-) mice, all groups, irrespective of the presence or absence of LTalpha on
      the donor or recipient cells, developed colitis and generated Th1, Th17, and
      Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation,
      with colitogenic but not naturally occurring Th17 cells, developed intestinal
      inflammation. The presence of naturally occurring Th17 cells in the colons of
      mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T
      cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high)
      T cells. CONCLUSIONS: Gut-associated lymphoid tissue structures are required to
      generate naturally occurring Th17 cells that have regulatory activities in normal
      intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during
      inflammation.

PMID- 22850183
TI  - Malnutrition in systemic sclerosis.
AB  - SSc is a chronic multi-system disease with wide-reaching consequences.
      Gastrointestinal features are present in over 90% of cases and these, together
      with other disease manifestations, may lead to nutritional decline. This produces
      substantial morbidity, including reliance on enteral support and even parenteral
      nutrition-dependent intestinal failure. These complications carry an associated
      mortality. Up to 18% of patients with SSc are reported to be at high risk of
      malnutrition [as assessed by Malnutrition Universal Screening Tool (MUST)
      criteria], with risk increasing with disease severity. Little is known about this
      decline, its rate of progression and how it affects the individual. Few case
      series report on nutritional interventions. Most current interventions are based
      on experience in other diseases. The development of specialist knowledge of SSc
      related gastrointestinal disease management and nutritional screening and
      interventions is required. This paper reviews current knowledge relating to
      malnutrition and its management in SSc.

PMID- 22850182
TI  - Determinants of Dutch general practitioners' nutrition and physical activity
      guidance practices.
AB  - OBJECTIVE: General practitioners (GP) are uniquely placed to guide their patients
      on nutrition and physical activity. The aims of the present study were to assess:
      (i) the extent to which GP guide on nutrition and physical activity; (ii) the
      determinants that cause GP to give guidance on nutrition and physical activity;
      and (iii) the extent to which these guidance practices have the same
      determinants. DESIGN: Cross-sectional study, mail questionnaire. SETTING: Dutch
      general practice. SUBJECTS: Four hundred and seventy-two GP in practice for 5-30
      years. RESULTS: Our study showed that the majority of GP had similar practices
      for both nutrition and physical activity guidance. Fair associations were found
      between nutrition and physical activity guidance practices. More than half of the
      explained variance in the models of physical activity guidance practices was
      improved by the inclusion of nutrition guidance practices in the models.
      Moreover, GP reported higher frequencies of physical activity guidance practices
      than nutrition guidance practices. Nutrition guidance practices predicted the
      same physical activity guidance practices. CONCLUSIONS: The majority of GP had
      similar practices for nutrition and physical activity guidance. GP were more
      inclined to guide their patients on physical activity than on nutrition. Self
      efficacy was found to be a determinant in most models for guidance practices.
      Guidance practices proved to be a mix of prevention and treatment components.
      Consequently, we advise raising the selfefficacy of GP by training in medical
      school and in continuing medical education. We also recommend the combination of
      both nutrition and physical activity guidance in general practice.

PMID- 22850181
TI  - Role of complement and NK cells in antibody mediated rejection.
AB  - Despite extensive research on T cells and potent immunosuppressive regimens that
      target cellular mediated rejection, few regimens have been proved to be effective
      on antibody-mediated rejection (AMR), particularly in the chronic setting. C4d
      deposition in the graft has been proved to be a useful marker for AMR; however,
      there is an imperfect association between C4d and AMR. While complement has been
      considered as the main player in acute AMR, the effector mechanisms in chronic
      AMR are still debated. Recent studies support the role of NK cells and direct
      effects of antibody on endothelium cells in a mechanism suggesting the presence
      of a complement-independent pathway. Here, we review the history, currently
      available systems and progress in experimental animal research. Although there
      are consistent findings from human and animal research, transposing the
      experimental results from rodent to human has been hampered by the differences in
      endothelial functions between species. We briefly describe the findings from
      patients and compare them with results from animals, to propose a combined
      perspective.

PMID- 22850184
TI  - Genetic deletion of low-density lipoprotein receptor-related protein 5 increases
      cartilage degradation in instability-induced osteoarthritis.
AB  - OBJECTIVE: The wingless-type MMTV integration site family (WNT) signalling
      pathway plays an important role in embryonic joint and bone development and has
      been associated with osteoporosis and osteoarthritis (OA). Loss-of-function
      mutations in low-density lipoprotein receptor-related protein 5 (LRP5), a WNT co
      receptor, result in low bone mass. Lrp5(-)(/)(-) mice also have low bone mass
      phenotypes. Recently an OA-susceptibility locus containing the LRP5 gene was
      suggested. We investigated the effects of loss of Lrp5 in joint biology in three
      different mouse models of OA. METHODS: Total body bone mineral parameters were
      measured by dual-energy X-ray absorptiometry. Trabecular and cortical bone
      parameters of tibia and femur were assessed ex vivo by peripheral quantitative
      CT. Osteoarthritic changes were induced in Lrp5(-)(/)(-) and wild-type C57Bl/6J
      mice using the surgically induced destabilization of the medial meniscus model
      and the chemically induced papain and collagenase model. The severity of joint
      disease was investigated by histological analysis of the knee joints. RESULTS:
      Bone mineral density and weight were significantly decreased in Lrp5(-)(/)(-)
      C57Bl/6J mice compared with their wild-type littermates. Surgically induced
      destabilization of the knee joint resulted in significantly increased cartilage
      degradation in the medial tibia of Lrp5(-)(/)(-) mice compared with wild-type
      control mice. In the medial femur, a similar trend was found but did not reach
      statistical significance. In the papain- and collagenase-induced models, these
      differences were not observed. Inflammation scores were comparable between wild
      type and Lrp5(-)(/)(-) mice. CONCLUSION: These data show that loss of function of
      Lrp5 increases cartilage degradation in mild instability-induced OA models in
      mice. Low bone mass density could have contributed to this effect.

PMID- 22850185
TI  - Elevated interleukin-32 expression in granulomatosis with polyangiitis.
AB  - OBJECTIVE: To evaluate the role of IL-32 in granulomatosis with polyangiitis
      (GPA) patients and the relationship between IL-32 and disease activity, as PR3
      has the ability to bind and activate IL-32, which has been described as a novel
      cytokine that induces inflammatory cytokines. METHODS: We investigated the level
      of IL-32, PR3, TNF-alpha and IL-6 in GPA patients by using ELISA. Northern blot
      was used to analyse the level of IL-32 mRNA in leucocytes of GPA patients. The
      intracellular colocalization of IL-32 and PR3 in leucocytes was examined by IF
      staining. RESULTS: We observed that IL-32 and PR3 levels in GPA patients were
      increased significantly when compared with normal individuals and each was
      tightly associated (P < 0.001). Northern blot analysis revealed that the mRNA
      level of IL-32 was prominently elevated in leucocytes of GPA patients. The
      intracellular colocalization of IL-32 and PR3 in leucocytes from GPA patients vs
      normal individuals was verified by IF staining. CONCLUSION: IL-32 level was
      elevated in GPA patients but its level was changed by treatment response. IL-32
      could be an index in GPA and play a role in the aetiology of GPA.

PMID- 22850186
TI  - Excess mortality in women of reproductive age from low-income countries: a
      Swedish national register study.
AB  - BACKGROUND: Cause-of-death statistics is widely used to monitor the health of a
      population. African immigrants have, in several European studies, shown to be at
      an increased risk of maternal death, but few studies have investigated cause
      specific mortality rates in female immigrants. METHODS: In this national study,
      based on the Swedish Cause of Death Register, we studied 27,957 women of
      reproductive age (aged 15-49 years) who died between 1988 and 2007. Age
      standardized mortality rates per 100,000 person years and relative risks for
      death and underlying causes of death, grouped according to the International
      Statistical Classification of Diseases and Related Health Problems, 10th
      Revision, were calculated and compared between women born in Sweden and in low-,
      middle- and high-income countries. RESULTS: The total age-standardized mortality
      rate per 100,000 person years was significantly higher for women born in low
      income (84.4) and high-income countries (83.7), but lower for women born in
      middle-income countries (57.5), as compared with Swedish-born women (68.1). The
      relative risk of dying from infectious disease was 15.0 (95% confidence interval
      10.8-20.7) and diseases related to pregnancy was 6.6 (95% confidence interval 2.6
      16.5) for women born in low-income countries, as compared to Swedish-born women.
      CONCLUSIONS: Women born in low-income countries are at the highest risk of dying
      during reproductive age in Sweden, with the largest discrepancy in mortality
      rates seen for infectious diseases and diseases related to pregnancy, a cause of
      death pattern similar to the one in their countries of birth. The World Bank
      classification of economies may be a useful tool in migration research.

PMID- 22850187
TI  - Psychosocial stress during pregnancy is related to adverse birth outcomes:
      results from a large multi-ethnic community-based birth cohort.
AB  - BACKGROUND: Prevalence rates of psychosocial stress during pregnancy are
      substantial. Evidence for associations between psychosocial stress and birth
      outcomes is inconsistent. This study aims to identify and characterize different
      clusters of pregnant women, each with a distinct pattern of psychosocial stress,
      and investigate whether birth outcomes differ between these clusters. METHODS:
      Latent class analysis was performed on data of 7740 pregnant women (Amsterdam
      Born Children and their Development study). Included constructs were depressive
      symptoms, state anxiety, job strain, pregnancy-related anxiety and parenting
      stress. RESULTS: Five clusters of women with distinct patterns of psychosocial
      stress were objectively identified. Babies born from women in the cluster
      characterized as 'high depression and high anxiety, moderate job strain' (12%)
      had a lower birth weight, and those in the 'high depression and high anxiety, not
      employed' cluster (15%) had an increased risk of pre-term birth. CONCLUSIONS:
      Babies from pregnant women reporting both high levels of anxiety and depressive
      symptoms are at highest risk for adverse birth outcomes.

PMID- 22850188
TI  - Regional assessment of PAHs contamination in SE Brazil using brown mussels (Perna
      perna Linnaeus 1758).
AB  - Cultured and native brown mussels (Perna perna Linnaeus 1758) were used to
      evaluate the contamination by PAHs in the SE Brazilian coastal zone. Mean
      concentrations of total PAH (38 parental and alkylated compounds) and cluster
      analysis revealed that: (i) mussel farms (32.7-70.1 ng g(-1)) are located in
      uncontaminated areas; (ii) coastal rockyshore areas (89.7 +/- 25.8 ng g(-1)) have
      low level of contamination; and (iii) the Guanabara Bay (760.9 +/- 456.3 ng g(
      1)) is chronically contaminated by hydrocarbons, which is consistent with
      previous results. PAH profiles and diagnostic ratios suggested mixed petrogenic
      and pyrolitic sources for group (ii) and petrogenic sources for group (iii). The
      levels of PAH in the cultured and native mussels are below threshold values for
      safe food, even in Guanabara Bay, and thus in such cases other contaminants and
      pathogens should be considered in order to evaluate the quality of shellfish for
      human consumption.

PMID- 22850189
TI  - Integration of multi-technology on oil spill emergency preparedness.
AB  - This paper focuses on the integration of technologies including Case-Based
      Reasoning (CBR), Genetic Algorithm (GA) and Artificial Neural Network (ANN) for
      establishing emergency preparedness for oil spill accidents. In CBR, the Frame
      method is used to define case representation, and the HEOM (Heterogeneous
      Euclidean-Overlap Metric) is improved to define the similarity of case
      properties. In GA, we introduce an Improved Genetic Algorithm (IGA) that achieves
      case adaptation, in which technologies include the Multi-Parameter Cascade Code
      method, the Small Section method for generation of an initial population, the
      Multi-Factor Integrated Fitness Function, and Niche technology for genetic
      operations including selection, crossover, and mutation. In ANN, a modified back
      propagation algorithm is employed to train the algorithm to quickly improve
      system preparedness. Through the analysis of 32 fabricated oil spill cases, an
      oil spill emergency preparedness system based on the integration of CBR, GA and
      ANN is introduced. In particular, the development of ANN is presented and
      analyzed. The paper also discusses the efficacy of our integration approach.

PMID- 22850191
TI  - High intakes of protein and processed meat associate with increased incidence of
      type 2 diabetes.
AB  - Diets high in protein have shown positive effects on short-term weight reduction
      and glycaemic control. However, the understanding of how dietary macronutrient
      composition relates to long-term risk of type 2 diabetes is limited. The aim of
      the present study was to examine intakes of macronutrients, fibre and protein
      sources in relation to incident type 2 diabetes. In total, 27 140 individuals,
      aged 45-74 years, from the population-based Malmo Diet and Cancer cohort, were
      included. Dietary data were collected with a modified diet history method,
      including registration of cooked meals. During 12 years of follow-up, 1709
      incident type 2 diabetes cases were identified. High protein intake was
      associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for
      highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01).
      When protein consumption increased by 5 % of energy at the expense of
      carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33),
      increased diabetes risk was observed. Intakes in the highest quintiles of
      processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR
      1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased
      risk. Intake of fibre-rich bread and cereals was inversely associated with type 2
      diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion,
      results from the present large population-based prospective study indicate that
      high protein intake is associated with increased risk of type 2 diabetes.
      Replacing protein with carbohydrates may be favourable, especially if fibre-rich
      breads and cereals are chosen as carbohydrate sources.

PMID- 22850190
TI  - Evaluation of polymorphisms in the sulfonamide detoxification genes NAT2, CYB5A,
      and CYB5R3 in patients with sulfonamide hypersensitivity.
AB  - OBJECTIVE: To determine whether polymorphisms in the sulfonamide detoxification
      genes, CYB5A (encoding cytochrome b(5)), CYB5R3 (encoding cytochrome b(5)
      reductase), or NAT2 (encoding N-acetyltransferase 2) were over-represented in
      patients with delayed sulfonamide drug hypersensitivity, compared with control
      patients who tolerated a therapeutic course of trimethoprim-sulfamethoxazole
      without adverse event. METHODS: DNA from 99 nonimmunocompromised patients with
      sulfonamide hypersensitivity who were identified from the Personalized Medicine
      Research Project at the Marshfield Clinic, and from 99 age-matched, race-matched,
      and sex-matched drug-tolerant controls, were genotyped for four CYB5A and five
      CYB5R3 polymorphisms, and for all coding NAT2 SNPs. RESULTS: CYB5A and CYB5R3
      SNPs were found at low allele frequencies (<3-4%), which did not differ between
      hypersensitive and tolerant patients. NAT2 allele and haplotype frequencies, as
      well as inferred NAT2 phenotypes, also did not differ between groups (60 vs. 59%
      slow acetylators). Finally, no difference in NAT2 status was found in a subset of
      patients with more severe hypersensitivity signs (drug reaction with eosinophilia
      and systemic symptoms) compared with tolerant patients. CONCLUSION: We found no
      evidence of a substantial involvement of these nine CYB5A or CYB5R3 polymorphisms
      in sulfonamide hypersensitivity risk, although minor effects cannot be completely
      ruled out. Despite careful medical record review and full resequencing of the
      NAT2 coding region, we found no association of NAT2 coding alleles with
      sulfonamide hypersensitivity (predominantly cutaneous eruptions) in this adult
      Caucasian population.

PMID- 22850192
TI  - A prospective study comparing histology and enteric enzyme function of patients
      with extrahepatic portal vein obstruction before and after shunt surgery.
AB  - BACKGROUND: This was a prospective observational study carried out to objectively
      assess the effect of shunt surgery on intestinal morphology and function in
      patients with extrahepatic portal vein obstruction (EHPVO) and correlate it with
      growth improvement. PATIENTS AND METHODS: Twenty patients who were operated upon
      for EHPVO were divided into two groups for the purpose of analysis depending on
      the outcome of surgery: group A--patients who underwent successful shunt surgery
      (n=14) and group B--patients who underwent splenectomy with devascularization
      (n=1) and those with thrombosed shunts (n=5). The patient groups were created on
      the basis of the type and outcome of the surgery and not prospective
      stratification. Growth parameters, endoscopy findings, duodenal histology, brush
      border enzyme activity, urinary D-xylose levels, fecal steatocrit, fecal alpha-1
      antitrypsin, serum growth hormone and insulin-like growth factor-1 levels, and
      quality-of-life scores were assessed before surgery and at a mean of 24.9 weeks
      after surgery. RESULTS: There was no significant difference between the
      preoperative and postoperative duodenal histology. Preoperative brush border
      lactase activity was significantly lower than normal and did not change
      significantly after surgery. EHPVO did not affect intestinal absorption or
      permeability. Shunt surgery resulted in significantly improved z scores for
      height after surgery as well as quality of life. There was no significant growth
      hormone resistance. CONCLUSION: Our patients did not have any significant
      malabsorption or abnormality in small intestinal structure and function when
      compared with established normal levels. There was no significant change in the
      above parameters after shunt surgery, although an improvement in growth was
      observed. Thus, factors other than enteropathy or other lesser known enteral
      factors seem to be responsible for the growth retardation observed in EHPVO and
      its subsequent improvement after shunt surgery.

PMID- 22850193
TI  - Corticosteroid replacement therapy in hepatoadrenal syndrome:  case report with a
      review of the literature.
AB  - In liver cirrhosis, hepatoadrenal syndrome has been described recently as a
      progressive impairment in the adrenocortical reserve, with deficient production
      or action of glucocorticoids resulting in adrenal insufficiency. Data on the
      treatment of this syndrome are scarce. We report a case of a 60-year-old male
      patient referred to our hospital because of rectal bleeding and bilateral leg
      swelling. He complained of marked weakness, bilateral leg swelling, and shortness
      of breath with exertion for the last 2 months. Biochemistry and imaging indicated
      liver cirrhosis. Because of the weakness and persistent hypotension, we performed
      a low-dose synacthen test, which indicated adrenal insufficiency (baseline
      cortisol level 1.8 MUg/dl, increasing to 3.5 and 3.7 MUg/dl at 20 and 30 min,
      respectively). The patient's general condition improved promptly after
      corticosteroid supplementation.

PMID- 22850195
TI  - Adaptive servo-ventilation - pressurization and oxygenation -.

PMID- 22850194
TI  - Optimization-based reconstruction of sparse images from few-view projections.
AB  - In this work, we investigate optimization-based image reconstruction from few
      view (i.e. less than ten views) projections of sparse objects such as coronary
      artery specimens. Using optimization programs as a guide, we formulate constraint
      programs as reconstruction programs and develop algorithms to reconstruct images
      through solving the reconstruction programs. Characterization studies are carried
      out for elucidating the algorithm properties of 'convergence' (relative to
      designed solutions) and 'utility' (relative to desired solutions) by using
      simulated few-view data calculated from a discrete FORBILD coronary-artery
      phantom, and real few-view data acquired from a human coronary-artery specimen.
      Study results suggest that carefully designed reconstruction programs and
      algorithms can yield accurate reconstructions of sparse images from few-view
      projections.

PMID- 22850196
TI  - Quantitative proteomic profiling of the promastigotes and the intracellular
      amastigotes of Leishmania donovani isolates identifies novel proteins having a
      role in Leishmania differentiation and intracellular survival.
AB  - Protozoan parasites of the genus Leishmania are important human pathogens that
      cycle between an extracellular promastigote stage residing in the sandflies and
      an intracellular amastigote stage colonizing the phagolysosomal compartment of
      the mammalian macrophages. Here, we used the isobaric tagging method to quantify
      the global proteomic differences between the promastigotes and the intracellular
      amastigotes of three different Leishmania donovani clones derived from the THP-1
      human macrophage cell line. We identified a substantial number of differentially
      modulated proteins involved in nutrient acquisition and energy metabolism, cell
      motility and cytoskeleton, transport, cell signaling and stress response.
      Proteins involved in vesicular trafficking and endocytosis like the rab7 GTP
      binding protein, GTP-binding proteins of the Ras superfamily and developmentally
      regulated GTP-binding protein 1 revealed enhanced expression and also a putative
      dynein heavy chain protein was found to be up-regulated in the amastigotes and it
      probably has a role in cargo transport inside the vesicles. Significantly, in the
      amastigotes the expression of a protein involved in glucose transport was
      increased eight to fifteen-fold, whereas concentrations of several proteins
      associated with cell motility and cytoskeleton were reduced. Thus, the
      quantitative proteomic analysis of L. donovani isolates sheds light on some novel
      proteins that may have a role in Leishmania differentiation and intracellular
      survival.

PMID- 22850197
TI  - Filamin isoforms in molluscan smooth muscle.
AB  - The role of filamin in molluscan catch muscles is unknown. In this work three
      proteins isolated from the posterior adductor muscle of the sea mussel Mytilus
      galloprovincialis were identified by MALDI-TOF/TOF MS as homologous to mammalian
      filamin. They were named FLN-270, FLN-230 and FLN-105, according to their
      apparent molecular weight determined by SDS-PAGE: 270kDa, 230kDa and 105kDa,
      respectively. Both FLN-270 and FLN-230 contain the C-terminal dimerization domain
      and the N-terminal actin-binding domain typical of filamins. These findings,
      together with the data from peptide mass fingerprints, indicate that FLN-270 and
      FLN-230 are different isoforms of mussel filamin, with FLN-230 being the
      predominant isoform in the mussel catch muscle. De novo sequencing data revealed
      structural differences between both filamin isoforms at the rod 2 segment, the
      one responsible for the interaction of filamin with the most of its binding
      partners. FLN270 but not FLN230 was phosphorylated in vitro by cAMP-dependent
      protein kinase. As for the FLN-105, it would be an N-terminal proteolytic
      fragment generated from the FLN-270 isoform or a C-terminally truncated variant
      of filamin. On the other hand, a 45-kDa protein that copurifies with mussel catch
      muscle filamins was identified as the mussel calponin-like protein. The fact that
      this protein coelutes with the FLN-270 isoform from a gel filtration
      chromatography suggests a specific interaction between both proteins.

PMID- 22850198
TI  - Words or wisdom. Re: making the most out of six systematic sextant biopsies.

PMID- 22850199
TI  - Words of wisdom. Re: Complications After Prostate Biopsy: Data From SEER
      Medicare.

PMID- 22850200
TI  - Words of wisdom. Re: a prospective, randomized EORTC intergroup phase 3 study
      comparing the oncologic outcome of elective nephron-sparing surgery and radical
      nephrectomy for low-stage renal cell carcinoma.

PMID- 22850201
TI  - Words of wisdom. Re: Hospital volume, utilization, costs, and outcomes of robot
      assisted laparoscopic radical prostatectomy.

PMID- 22850202
TI  - Words of wisdom. Re: Vitamin E and the risk of prostate cancer. The Selenium and
      Vitamin E Cancer Prevention Trial (SELECT).

PMID- 22850203
TI  - Words of wisdom. Re: antioxidants for male subfertility.

PMID- 22850204
TI  - Adolescent neuregulin 1 heterozygous mice display enhanced behavioural
      sensitivity to methamphetamine.
AB  - Methamphetamine use triggers psychosis in genetically vulnerable individuals,
      however the exact nature of this genetic predisposition requires elucidation. In
      addition, adolescence may be a particular period of neurodevelopmental
      vulnerability to the actions of methamphetamine; interestingly, this period
      coincides with a higher likelihood of onset of schizophrenia and drug
      experimentation. In the current study we investigated whether adolescent mice
      heterozygous for the schizophrenia susceptibility gene neuregulin 1 (Nrg1 HET
      mice) exhibit altered behavioural responses to methamphetamine (0.6 or 2.4mg/kg)
      in schizophrenia-relevant paradigms. The responses measured were locomotor
      activity in the open field test and sensorimotor gating function in the prepulse
      inhibition of startle paradigm (PPI). Adolescent Nrg1 HET mice displayed a
      subtle, transient, novelty-induced baseline locomotor hyperactivity over days,
      and a selective PPI deficit at the prepulse intensity-interstimulus interval
      (ISI) combination of 82dB-64ms. Adolescent Nrg1 HET mice were more sensitive to
      the locomotor stimulatory effects of an acute, low-dose of methamphetamine
      (0.6mg/kg) relative to wild-type (WT) controls. The augmented response to acute
      methamphetamine observed in Nrg1 HET mice disappeared with repeated, daily dosing
      over 7days. Methamphetamine did not affect average PPI (total or across different
      prepulse intensities), however 0.6mg/kg methamphetamine triggered a PPI deficit
      selectively in Nrg1 HET mice but not WT mice at 82dB-256ms. Our results show that
      locomotor hyperactivity in Nrg1 HET mice, albeit subtle, can manifest much
      earlier than previously reported and that Nrg1 may confer vulnerability to the
      acute actions of methamphetamine, a drug known to trigger psychotic reactions in
      humans.

PMID- 22850205
TI  - Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in
      pharmacoresistant depression using either high-frequency left or low-frequency
      right prefrontal rTMS.
AB  - BACKGROUND: Functional neuroimaging studies have suggested similar mechanisms
      underlying antidepressant effects of distinct therapeutics. OBJECTIVE: This study
      aimed to determine and compare functional brain patterns underlying the
      antidepressant response of 2 distinct protocols of repetitive transcranial
      magnetic stimulation (rTMS). METHODS: 99mTc-ECD SPECT was performed before and
      after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed
      patients with major depression, using high frequency (10Hz) left-side stimulation
      in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients.
      Efficiency of rTMS response was defined as at least 50% reduction of the baseline
      Beck Depression Inventory score. We compared the whole-brain voxel-based brain
      SPECT changes in perfusion after rTMS, between responders and non-responders in
      the whole sample (p<0.005, uncorrected), and separately in the subgroup of
      patients with left- and right-stimulation. RESULTS: Before rTMS, the left- and
      right-prefrontal stimulation groups did not differ from clinical data and brain
      SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically
      equivalent in the two groups of patients. In the whole-group of responder
      patients, a perfusion decrease was found after rTMS, in comparison to non
      responders, within the left perirhinal cortex (BA35, BA36). This result was
      secondarily confirmed separately in the two subgroups, i.e. after either left
      stimulation (p=0.017) or right stimulation (p<0.001), without significant
      perfusion differences between these two subgroups. CONCLUSIONS: These data show
      that distinct successful rTMS protocols induce equivalent brain functional
      changes associated to antidepressive efficiency, consisting to a remote brain
      limbic activity decrease within the left perirhinal cortex. However, these
      results will have to be confirmed in a double-blind randomized trial using a sham
      control group.

PMID- 22850206
TI  - Efficacy of sitagliptin on blood glucose fluctuation in Japanese type 2 diabetic
      patients with basal-supported oral therapy.
AB  - We retrospectively investigated the effect of adding dipeptidyl peptidase-4 (DPP
      4) inhibitor and tapering sulfonylurea on blood glucose fluctuation in Asian
      patients with type 2 diabetes mellitus under basal-supported oral therapy (BOT). 
      We recruited twenty-two consecutive Japanese patients with type 2 diabetes
      mellitus who had blood glucose fluctuation under the combination therapy of
      insulin glargine and glimepiride and had sitagliptin initiated with glimepiride
      tapared.  Their hemoglobin A1c levels and mean blood glucose profiles of seven
      points in self-monitoring blood glucose (SMBG) were 7.4 +/- 0.6% and 8.6 +/- 2.0
      mmol/L, respectively.  Sitagliptin was initiated with the dose of 50 mg per day
      and titrated up to 100 mg per day when necessary.  Glimepiride was withdrawn if
      possible.  Blood glucose fluctuation was evaluated with SMBG by calculating M
      value, its range (the difference of maximum and minimum blood glucose levels),
      and its coefficient of variation (CV).  Two months after sitagliptin add-on, M
      value was decreased from 19 +/- 13 to 13 +/- 8 (p = 0.04).  Blood glucose range
      and CV were also improved from 9.6 +/- 2.9 mmol/L to 7.9 +/- 2.6 mmol/L (p =
      0.01), and from 33 +/- 8% to 29 +/- 8% (p < 0.01), respectively.  Hemoglobin A1c
      levels and mean blood glucose profiles were unchanged (p = 0.93 and 0.47).  In
      conclusion, blood glucose fluctuation was significantly improved two months after
      adding sitagliptin and tapering glimepiride in type 2 diabetic Japanese patients
      who were treated by BOT with insulin glargine and glimepiride.

PMID- 22850207
TI  - Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea.
AB  - Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia
      cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8alpha
      hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8alpha
      hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4
      9). The structures of the new compounds were determined by 1D and 2D NMR
      experiments and by comparison with the structure of compound 1, whose relative
      stereochemistry was determined by X-ray analysis. The isolated compounds were
      evaluated for their cancer chemopreventive potential based on their ability to
      inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-alpha)
      induced NF-kappaB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-alpha
      induced NF-kappaB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 MUM,
      respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity
      with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 MUM, respectively.

PMID- 22850208
TI  - Dipeptidyl peptidase-4 inhibitor with beta-amino amide scaffold: synthesis, SAR
      and biological evaluation.
AB  - Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective
      treatments for type 2 diabetes. Several series of beta-amino amide containing
      piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4.
      Finally compound 5m was selected for further evaluation.

PMID- 22850209
TI  - Important role of Maillard reaction in the protective effect of heat-processed
      ginsenoside Re-serine mixture against cisplatin-induced nephrotoxicity in LLC-PK1
      cells.
AB  - The aim of the present study was to verify the important role of Maillard
      reaction in the protective effect of heat-processed ginsenoside Re-serine mixture
      against oxidative stress-induced nephrotoxicity. The free radical-scavenging
      activity of ginsenoside Re-serine mixture was increased by heat-processing.
      Ginsenoside Re was transformed into less-polar ginsenosides such as Rg(2), Rg(6)
      and F(4) by heat-processing, and the glucose molecule at carbon-20 was separated.
      The improved-free radical-scavenging activity by heat-processing was mediated by
      the generation of antioxidant Maillard reaction products (MRPs) from the reaction
      of glucose with serine. Moreover, MRPs from ginsenoside Re-serine mixture showed
      protective effect against cisplatin-induced renal epithelial cell damage.

PMID- 22850210
TI  - Exploration of ring size in a series of cyclic vicinal diamines with sigma1
      receptor affinity.
AB  - Imidazolidine and 1,4-diazepane analogs of N-(2-benzofuranyl)methyl-N'-(4
      alkoxybenzyl)piperazines were prepared to explore the effect of ring contraction
      and expansion on sigma receptor affinity and subtype selectivity within a series
      of cyclic diamines. In vitro receptor binding assays revealed that all cyclic
      vicinal diamines possessed affinity and selectivity for sigma(1) receptors. The
      imidazolidines possessed nanomolar sigma(1) affinities (K(i)=6.45-53.5 nM), and
      relatively low levels of subtype selectivity (sigma(2)/sigma(1)=58-237). However,
      the piperazines and diazepanes achieved picomolar sigma(1) interactions, with
      K(i) ranges of 0.05-10.28 and 0.10-0.194 nM, respectively. Moreover, the
      piperazines and diazepanes showed excellent discrimination over the sigma(2)
      receptor, with sigma(1) selectivities of 143-16140 and 220-11542, respectively.

PMID- 22850211
TI  - Hybrid molecules of carvacrol and benzoyl urea/thiourea with potential
      applications in agriculture and medicine.
AB  - Benzoyl phenyl urea, a class of insect growth regulator's acts by inhibiting
      chitin synthesis. Carvacrol, a naturally occurring monoterpenoid is an effective
      antifungal agent. We have structurally modified carvacrol (2-methyl-5-[1
      methylethyl] phenol) by introducing benzoylphenyl urea linkage. Two series of
      benzoylcarvacryl thiourea (BCTU, 4a-f) and benzoylcarvacryl urea (BCU, 5a-f)
      derivatives were prepared and characterized by elemental analysis, IR, (1)H and
      (13)C NMR and Mass spectroscopy. Derivatives 4b, 4d, 4e, 4f and 5d, 5f showed
      comparable insecticidal activity with the standard BPU lufenuron against
      Dysdercus koenigii. BCTU derivatives 4c, 4e and BCU 5c showed good antifungal
      activity against phytopathogenic fungi viz. Magnaporthe grisae, Fusarium
      oxysporum, Dreschlera oryzae; food spoilage yeasts viz. Debaromyces hansenii,
      Pichia membranifaciens; and human pathogens viz. Candida albicans and
      Cryptococcus neoformans. Compounds 5d, 5e and 5f showed potent activity against
      human pathogens. Moderate and selective activity was observed for other
      compounds. All the synthesized compounds were non-haemolytic. These compounds
      have potential application in agriculture and medicine.

PMID- 22850212
TI  - Selected chromone derivatives as inhibitors of monoamine oxidase.
AB  - A previous study has shown that a series of C6-benzyloxy substituted chromones
      exhibit high binding affinities for human monoamine oxidase (MAO) B. In an
      attempt to discover additional chromones with potent and selective MAO-B
      inhibitory potencies and to further examine the structure-activity relationships
      of MAO-B inhibition by chromones, the series was expanded with homologues
      containing polar functional groups on C3 of the chromone ring. The results
      demonstrate that 6-[(3-bromobenzyl)oxy]chromones containing acidic and aldehydic
      functional groups on C3 act as potent reversible MAO-B inhibitors with IC(50)
      values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1
      benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the
      chromones also were potent MAO-B inhibitors with IC(50) values ranging from 4 to
      11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the
      chromone ring, however, exhibit MAO-B inhibition potencies that are several
      orders of magnitude weaker. High potency inhibitors of MAO-B may find application
      in the therapy of neurodegenerative disorders such as Parkinson's disease.

PMID- 22850213
TI  - Synthesis and in vitro evaluation of new chloroquine-chalcone hybrids against
      chloroquine-resistant strain of Plasmodium falciparum.
AB  - The control of malaria has been complicated with increasing resistance of
      malarial parasite against existing antimalarials. Herein, we report the synthesis
      of a new series of chloroquine-chalcone based hybrids (8-22) and their
      antimalarial efficacy against both chloroquine-susceptible (3D7) and chloroquine
      resistant (K1) strains of Plasmodium falciparum. Most of the compounds showed
      enhanced antimalarial activity as compared to chloroquine in chloroquine
      resistant (K1) strain of Plasmodium falciparum. Furthermore, to unfold the
      mechanism of action of these synthesized hybrid molecules, we carried out hemin
      dependent studies, in which three compounds were found to be active.

PMID- 22850215
TI  - Structural requirements for the antitubercular quaternized triflupromazine
      pharmacophore.
AB  - Quaternized triflupromazine derivatives (QTDs) must possess benzyl groups
      attached to the quaternary nitrogen in order to have significant antitubercular
      potency. Replacing the quaternary amine with a triazole abolishes antitubercular
      activity. A modest halogen substitution effect exists, with the 4-bromophenyl QTD
      3 having the best selectivity index (>21). All N-benzyl QTDs 1-4 similarly
      inhibit non-replicating, persistent Mycobacterium tuberculosis with MIC<8 MUM,
      and compounds 1-3 were all nontoxic to mammalian cells in vitro (IC(50)>128 MUM).

PMID- 22850214
TI  - Identification of selective tubulin inhibitors as potential anti-trypanosomal
      agents.
AB  - The potency of a series of sulfonamide tubulin inhibitors against the growth of
      Trypanosoma brucei (T. brucei), as well as human cancer and primary fibroblast
      cells were evaluated with the aim of determining whether compounds that
      selectively inhibit parasite proliferation could be identified. Several compounds
      showed excellent selectivity against T. brucei growth, and have the potential to
      be used for the treatment of Human African trypanosomiasis. A T. brucei tubulin
      protein homology model was built based on the crystal structure of the bovine
      tubulin. The colchicine-binding domain, which is also the binding site of the
      tested sulfonamide tubulin inhibitors, showed clear differences between the
      tubulin structures and presumably explained the selectivity of the compounds.

PMID- 22850216
TI  - Evaluation of siRNAs that contain internal variable-length spacer linkages.
AB  - The most widely accepted mechanism of RNAi-silencing involves the RNA-induced
      silencing complex (RISC) liberating the active antisense strand from the sense
      strand of an siRNA duplex to form an active RISC-antisense complex. This involves
      cleaving the sense strand between positions 9 and 10 from the 5' end of the
      strand prior to dissociation. Destabilizing modifications near the center of the
      duplex in some cases can enhance the efficacy of the resultant construct and may
      trigger an alternative mechanism through which the sense strand is removed. By
      introducing alkyl spacers of varying lengths near or within the sense strand's
      cleavage site, this study illustrates that siRNAs, in most cases, retained potent
      RNAi-silencing activity. Our results highlight that by substituting the scissile
      phosphodiester linkage on the sense strand with non-cleavable alkyl chains
      provides a novel and alternative method to destabilize the central region of
      siRNAs.

PMID- 22850217
TI  - The RNA-binding protein xCIRP2 is involved in apoptotic tail regression during
      metamorphosis in Xenopus laevis tadpoles.
AB  - Frog metamorphosis induced by thyroid hormone (TH) involves not only cell
      proliferation and differentiation in reconstituted organs such as limbs, but also
      apoptotic cell death in degenerated organs such as tails. However, the molecular
      mechanisms directing the TH-dependent cell fate determination remain unclear. We
      have previously identified from newts an RNA-binding protein (nRBP) acting as the
      regulator governing survival and death in germ cells during spermatogenesis. To
      investigate the molecular events leading the tail resorption during
      metamorphosis, we analyzed the expression, the functional role in apoptosis, and
      the regulation of xCIRP2, a frog homolog of nRBP, in tails of Xenopus laevis
      tadpoles. At the prometamorphic stage, xCIRP2 protein is expressed in fibroblast,
      epidermal, nerve, and muscular cells and localized in their cytoplasm. When
      spontaneous metamorphosis progressed, the level of xCIRP2 mRNA remained unchanged
      but the amount of the protein decreased. In organ cultures of tails at the
      prometamorphic stage, xCIRP2 protein decreased before their lengths shortened
      during TH-dependent metamorphosis. The inhibition of calpain or proteasome
      attenuated the TH-induced decrease of xCIRP2 protein in tails, impairing their
      regression. These results suggest that xCIRP2 protein is downregulated through
      calpain- and proteasome-mediated proteolysis in response to TH at the onset of
      metamorphosis, inducing apoptosis in tails and thereby degenerating them.

PMID- 22850218
TI  - Impact of folic acid fortification of flour on neural tube defects: a systematic
      review.
AB  - OBJECTIVE: To review the impact of folic acid fortification of flour on the
      prevalence of neural tube defects (NTD). DESIGN: Systematic review of the
      literature on MEDLINE via PubMed, Scopus, OvidSP and LILACS (Latin American and
      Caribbean Health Sciences Literature) reporting the impact of folic acid
      fortification of flour on the prevalence of NTD in 2000-2011. Focusing on
      Santiago of Chile's birth defects registry (1999-2009) and the monitoring of
      flour fortification, we analysed the prevalence (NTD cases/10 000 births) pre and
      post flour fortification and the percentile distribution of folic acid content in
      flour (2005-2009). We explored the potential association between median folic
      acid in flour (mg/kg) and the prevalence of NTD. SETTING: Chile, Argentina,
      Brazil, Canada, Costa Rica, Iran, Jordan, South Africa and the USA. SUBJECTS:
      Live births and stillbirths. RESULTS: Twenty-seven studies that met inclusion
      criteria were evaluated. Costa Rica showed a significant reduction in NTD (~60
      %). Prevalence in Chile decreased from 18.6 to 7.3/10 000 births from 1999 to
      2007 and showed a slight increase to 8.5 in 2008-2009, possibly due to changes in
      fortification limits. When we related the prevalence of NTD with levels of flour
      fortification, the lowest prevalence was observed at a folic acid level of 1.5
      mg/kg. CONCLUSIONS: Fortification of flour with folic acid has had a major impact
      on NTD in all countries where this has been reported. Chile showed a 55 %
      reduction in NTD prevalence between 1999 and 2009. There is a need to constantly
      monitor the levels of flour fortification to maximize benefits and prevent the
      potential risk of folic acid excess, moreover to be vigilant for any new adverse
      effects associated with excess.

PMID- 22850219
TI  - Type 1 (sub-retinal pigment epithelial) neovascularization in central serous
      chorioretinopathy masquerading as neovascular age-related macular degeneration.
AB  - PURPOSE: The purpose of this study was to describe clinical and multimodal
      imaging features of patients with Type 1 neovascularization who lack findings of
      age-related macular degeneration but instead have features consistent with long
      standing central serous chorioretinopathy (CSC). METHODS: Nonconsecutive,
      retrospective, observational case series. Two groups of patients were identified
      and analyzed. Group 1 included patients presenting with Type 1 neovascularization
      who at the time of diagnosis were found to have findings more consistent with
      long-standing CSC than age-related macular degeneration. Group 2 included
      patients with a known history of CSC who developed Type 1 neovascularization over
      their course of follow-up. Clinical histories and multimodal imaging findings
      (color and red-free photography, fundus autofluorescence imaging, fluorescein
      angiography, indocyanine green angiography, spectral domain optical coherence
      tomography, and enhanced depth imaging optical coherence tomography) were
      analyzed. RESULTS: Twenty-seven eyes of 22 patients were identified. Thirteen
      patients presented with Type 1 neovascularization thought to be secondary to CSC
      (Group 1), and 9 patients with CSC were observed to develop Type 1
      neovascularization over their course of follow-up (Group 2). Eight patients (36%)
      had polypoidal neovascular structures within their Type 1 neovascular lesions, of
      which 4 (18% of all patients) had bilateral Type 1 neovascularization. The mean
      age of patients was 61 years (range, 48-76 years), and the median age was 58.5
      years. Thirteen patients (59%) were men. For those patients in Group 2, the mean
      duration between diagnosis of CSC and detection of Type 1 neovascularization was
      139 months (range, 7-365 months). The mean subfoveal choroidal thickness was 354
      MUm (range, 186-666 MUm). CONCLUSION: Some patients presenting with Type 1
      neovascularization may have clinical and multimodal imaging findings more
      consistent with long-standing CSC than with age-related macular degeneration.
      These patients are more likely to be younger, men, have thicker choroids, and
      have a higher prevalence of polypoidal neovasculopathy than those patients with
      Type 1 neovascularization secondary to age-related macular degeneration. Proper
      identification of these patients may have implications for their natural course
      and management.

PMID- 22850220
TI  - Errors during the preparation of drug infusions: a randomized controlled trial.
AB  - BACKGROUND: We investigated the extent and frequency of dose errors and treatment
      delays made as a consequence of preparing drug infusions at the bedside, rather
      than using pre-filled syringes. METHODS: Forty-eight nurses with critical care
      experience volunteered to take part in this randomized, blinded, controlled study
      conducted in the simulation centre of an urban hospital. They assisted in the
      management of a simulated patient with septic shock. Vasopressor infusions were
      prepared either by diluting concentrated drugs from ampoules or were provided in
      syringes pre-filled beforehand by an intensive care unit resident. RESULTS: The
      time taken for the infusion to be started and the final concentration of the
      drugs were measured. We also measured the concentration of infusions prepared by
      a pharmacist and a pharmaceutical company. Nurses took 156 s to start infusions
      when using pre-filled syringes compared with 276 s when preparing them de novo, a
      mean delay of 106 s [95% confidence interval (CI) 73-140 s, P<0.0001]. One
      infusion prepared from ampoules contained one-fifth of the expected concentration
      of epinephrine; another contained none at all. Medication errors were 17.0 times
      less likely when pre-filled syringes were used (95% CI 5.2-55.5), and infusions
      prepared by pharmacy and industry were significantly more likely to contain the
      expected concentration (P<0.001 for norepinephrine and P=0.001 for epinephrine).
      CONCLUSIONS: Providing drug infusions in syringes pre-filled by pharmacists or
      pharmaceutical companies would reduce medication errors and treatment delays, and
      improve patient safety. However, this approach would have substantial financial
      implications for healthcare providers, especially in less developed countries.

PMID- 22850221
TI  - Do technical skills correlate with non-technical skills in crisis resource
      management: a simulation study.
AB  - BACKGROUND: Both technical skills (TS) and non-technical skills (NTS) are key to
      ensuring patient safety in acute care practice and effective crisis management.
      These skills are often taught and assessed separately. We hypothesized that TS
      and NTS are not independent of each other, and we aimed to evaluate the
      relationship between TS and NTS during a simulated intraoperative crisis
      scenario. METHODS: This study was a retrospective analysis of performances from a
      previously published work. After institutional ethics approval, 50
      anaesthesiology residents managed a simulated crisis scenario of an
      intraoperative cardiac arrest secondary to a malignant arrhythmia. We used a
      modified Delphi approach to design a TS checklist, specific for the management of
      a malignant arrhythmia requiring defibrillation. All scenarios were recorded.
      Each performance was analysed by four independent experts. For each performance,
      two experts independently rated the technical performance using the TS checklist,
      and two other experts independently rated NTS using the Anaesthetists' Non
      Technical Skills score. RESULTS: TS and NTS were significantly correlated to each
      other (r=0.45, P<0.05). CONCLUSIONS: During a simulated 5 min resuscitation
      requiring crisis resource management, our results indicate that TS and NTS are
      related to one another. This research provides the basis for future studies
      evaluating the nature of this relationship, the influence of NTS training on the
      performance of TS, and to determine whether NTS are generic and transferrable
      between crises that require different TS.

PMID- 22850222
TI  - Prediction of treatment outcomes in patients with chest wall sarcoma: evaluation
      with PET/CT.
AB  - OBJECTIVE: The aim of this study was to investigate the prognostic implications
      of (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed
      tomography in patients with chest wall sarcoma. METHODS: Positron emission
      tomography/computed tomography scans of 42 patients (mean age: 46 years) with
      chest wall sarcomas were analyzed. Pathologic confirmation was obtained by
      surgical specimens in all patients. Tumor grade assessed by Ki-67 (MIB-1)
      immunohistochemical analysis and expression of glucose transporter protein 1 were
      compared with a maximum standardized uptake value. Univariate and multivariate
      analyses were conducted for estimates of overall and event-free survivals.
      RESULTS: The median maximum standardized uptake value of the tumor was 10.2 and
      the median MIB-1 index of the tumor was 32.5%. Glucose transporter protein 1
      expression was found in 29 patients (69%). Univariate analyses revealed that
      surgery, chemotherapy, MIB-1 labeling index (cut-off 32.5%), MIB-1 grade, glucose
      transporter protein 1 expression and maximum standardized uptake value were
      possible predictors for overall and event-free survival. Multivariate analysis
      revealed that surgery (hazard ratio, 4.852; P = 0.017), maximum standardized
      uptake value (hazard ratio, 3.077; P = 0.037) and MIB-1 labeling index (hazard
      ratio, 6.549; P = 0.003) were independent predictors of event-free survival. In
      addition, surgery (hazard ratio, 4.092; P = 0.021) and maximum standardized
      uptake value (hazard ratio, 2.968; P = 0.027) were independent predictors of
      overall survival. CONCLUSIONS: (18)F-2-fluoro-2-deoxy-d-glucose positron emission
      tomography/computed tomography allows the prediction of prognosis after treatment
      in patients with chest wall sarcoma and may be useful in selecting high-risk
      patients for more risk-adapted treatments.

PMID- 22850223
TI  - Discrepancies between public perceptions and epidemiological facts regarding
      cancer prognosis and incidence in Japan: an Internet survey.
AB  - BACKGROUND: This study investigates discrepancies between Japanese public
      perceptions and epidemiological facts regarding cancer prognosis and lifetime
      incidence, as well as factors that correlate with public perceptions. METHODS: We
      conducted a cross-sectional Internet survey with 2369 Japanese survey registrants
      without a history of cancer. Survey registrants were selected so that
      distributions of gender, age and place of residence (prefecture) reflected 2010
      national census data as much as possible. The questionnaire included questions
      about their perceptions of 5-year survival rates for cancer in general and 19
      site-specific cancers, as well as their perceptions of cumulative lifetime cancer
      incidence rate among Japanese men and women. RESULTS: The distribution of
      respondent answers regarding the 5-year survival rate for cancer in general and
      19 site-specific cancers varied widely from epidemiological data. Multiple
      regression analyses revealed that in some cancers, respondents who were of older
      age, who were female and who had a family/friend with a cancer history were
      significantly more likely to provide higher estimates regarding the 5-year
      survival rates. Respondents who correctly estimated cumulative lifetime cancer
      incidence rates among Japanese men and women were 8.5 and 33.1%, respectively.
      Respondents who were young, who had a higher educational background and who had a
      family/friend with a cancer history were significantly more likely to provide
      higher estimates of cumulative lifetime cancer incidence rates. CONCLUSIONS: Our
      study revealed wide discrepancies between Japanese public perceptions and
      epidemiological facts for cancer prognosis and incidence. Accordingly, more
      efforts should be made to bridge the gap between incorrect perceptions and
      epidemiological facts.

PMID- 22850224
TI  - Low-power laser therapy for repairing acute and chronic-phase bone lesions.
AB  - To evaluate the therapeutic activity of low-power laser (InGaAlP: 670 nm/30 mW),
      at doses of 90 J/cm(2), on the process of acute and chronic-phase repair of bone
      lesions of Wistar rats. Sixty-three adult males were divided into nine groups
      subjected to bone injury, in order to form the following treatments: T1
      (control); T2 (acute-phase); T3 (chronic-phase) which were subdivided into three
      subgroups (n=7), analyzed on the 9th, 17th and 28th days post-surgery, after a
      period of daily treatment with laser. The animals with acute-phase treatment
      presented a more extensive endochondral ossification process. Laser-treated
      animals showed significant increases in serum alkaline phosphatase levels and had
      an effect on biomechanical property, resulting in a gradual increase in bone
      stiffness. Laser therapy aided the bone consolidation process and favored the
      physiopathologic mechanisms involved in bone tissue repair, and its effects were
      more prominent when treatment started during the acute phase of the injury.

PMID- 22850225
TI  - Rumen fermentation and microbial population in lactating dairy cows receiving
      diets containing oilseeds rich in C-18 fatty acids.
AB  - Sixteen Holstein rumen-cannulated primiparous milking dairy cows were fed a
      control diet (CN) based on maize silage and soyabean meal during a 4-week period
      before the start of a 21-d experiment with oilseeds containing high concentration
      of linoleic acid (LinolaTM) or linolenic acid (NuLinTM). Thereafter, four cows
      received ad libitum one of each of four dietary treatments comprising of CN,
      Linola (LN), NuLin (NL) and LN/NL (50/50 % combination). Each LN, NL and LN/NL
      treatment contained 6 % oil of DM. Rumen digesta samples were collected on days
      6, 11, 16 and 21 and milk samples on days 13, 15 and 17. There were no effects
      (P>0.05) of the oilseeds on pH and concentrations of NH3-N and total volatile
      fatty acids, while the acetate:propionate ratio was decreased (P< 0.05). The
      oilseeds also decreased (P< 0.05) protozoa and increased (P< 0.1) total
      cellulolytic bacteria in rumen fluid, especially when containing high dietary
      linoleic acid (P< 0.05). The milk protein concentration was increased (P< 0.1) by
      the dietary linoleic acid, which produced most beneficial results. It was
      concluded that supplements of linoleic acid in diets of ruminants might
      contribute to better digestion of dietary fibre and increased quality of milk.

PMID- 22850226
TI  - Simulated and measured dose response characteristics of detectors used for CT
      dosimetry.
AB  - A CT-SD16 semiconductor detector was calibrated in terms of the computed
      tomography (CT) air kerma index for the integration length L = 100 mm,
      C(K,PMMA,100), in the cylindrical CT head and body dosimetry phantoms using a
      DCT10 pencil ionization chamber as a reference instrument. Using IEC RQT 9 120-kV
      x-ray radiation quality and 25-62.5 mm nominal beam widths free in air, a
      C(K,PMMA,100)(DCT10)/C(K,PMMA,100)(CT-SD16) ratio of 0.97 was observed, while in
      the centre of 300 mm long CT head and body dosimetry phantoms,
      C(K,PMMA,100)(DCT10)/C(K,PMMA,100)(CT-SD16) ratios ranged from 1.02 to 1.09.
      Using IEC RQT 8-10 radiation qualities free in air, Monte Carlo simulated dose
      response characteristics of CT-SD16 and DCT10 were comparable with those obtained
      from the measurements. Simulations were also used to determine
      C(K,PMMA,100)(DCT10) in the centre of the CT head and body phantoms. At IEC RQT 9
      and 25-62.5 mm nominal beam widths, the relative values of the simulated dose
      agreed with the measured values within 2-10% for the head and body phantoms,
      respectively. A k(q) correction factor between dose measurements in the phantom
      and free in air was determined for the model of DCT10 and for the real detectors
      using measured C(K,PMMA,100) data. Simulations were performed using the EGSnrc
      CAVRZ code.

PMID- 22850227
TI  - Dose optimization for different medical imaging tasks from exposure index,
      exposure control factor, and MAS in digital radiography.
AB  - In radiographic examination, not all medical imaging tasks require the same level
      of image quality or diagnostic information. Criteria should be established for
      different imaging tasks to avoid excessive doses where there is no clear net
      benefit in the diagnosis or the image quality. An exposure index provided by
      manufacturers would be a useful tool for this purpose. This study aims to
      establish an optimum exposure index to be used as a guideline for clinical
      imaging tasks to minimize radiation exposure for chest digital radiography. A
      three-level classification of image quality (high, medium, and low) for chest
      imaging tasks was carried out. An anthropomorphic phantom was employed to
      establish minimum exposure index and exposure (mAs) for clinical imaging task
      type I (corresponding to high image quality). The exposures of medium and low
      quality images derived from it. Thirty patients were exposed consecutively with
      these optimized exposure factors, and clinical tasks were considered, while
      another 30 patients were exposed with the exposure factors routinely used in
      practice. Image quality was assessed objectively by a consensus panel. The
      optimized exposure provided a significant reduction of the mean exposure index
      from 1,556 to 1,207 (p < 0.0001) and mean patient's entrance surface dose from
      0.168 mGy to 0.092 mGy (p < 0.0001). The results show that a clinical-task
      determined radiographic procedure is more conducive to radiation protection of
      patients. In this study, the posteroanterior chest imaging examination was chosen
      as an example. This procedure can also apply to other body parts and views.

PMID- 22850228
TI  - The effectiveness of mitigation for reducing radon risk in single-family
      Minnesota homes.
AB  - Increased lung cancer incidence has been linked with long-term exposure to
      elevated residential radon. Experimental studies have shown that soil ventilation
      can be effective in reducing radon concentrations in single-family homes. Most
      radon mitigation systems in the U.S. are installed by private contractors. The
      long-term effectiveness of these systems is not well known, since few state radon
      programs regulate or independently confirm post-mitigation radon concentrations.
      The effectiveness of soil ventilation systems in Minnesota was measured for 140
      randomly selected clients of six professional mitigators. Homeowners reported pre
      mitigation radon screening concentrations that averaged 380 Bq m (10.3 pCi L).
      Long term post-mitigation radon measurements on the two lowest floors show that,
      even years after mitigation, 97% of these homes have concentrations below the 150
      Bq m U.S. Environmental Protection Agency action level. The average post
      mitigation radon in the houses was 30 Bq m, an average observed reduction of
      >90%. If that reduction was maintained over the lifetime of the 1.2 million
      Minnesotans who currently reside in single-family homes with living space radon
      above the EPA action level, approximately 50,000 lives could be extended for
      nearly two decades by preventing radon-related lung cancers.

PMID- 22850229
TI  - Determination of in vitro lung solubility and intake-to-dose conversion factor
      for tritiated lanthanum nickel aluminum alloy.
AB  - A sample of tritiated lanthanum nickel aluminum alloy (LaNi4.25Al0.75 or LANA.75)
      similar to that used at the Savannah River Site Tritium Facilities was analyzed
      to estimate the particle size distribution of this metal tritide powder and the
      rate at which this material dissolves in the human respiratory tract after it is
      inhaled. This information is used to calculate the committed effective dose
      received by a worker after inhaling the material. These doses, which were
      calculated using the same methodology given in the U.S. Department of Energy
      Tritium Handbook, are presented as inhalation intake-to-dose conversion factors
      (DCF). The DCF for this metal tritide was determined to be 9.4 * 10 Sv Bq, which
      is less than the DCF for tritiated water. Therefore, the radiation worker
      bioassay programs designed for tritiated water are adequate to monitor for
      intakes of this material.

PMID- 22850231
TI  - Cylindrical waveguide electromagnetic exposure system for biological studies with
      unrestrained mice at 1.9 GHz.
AB  - This paper presents the development of an in vivo exposure system for exposing
      small rodents. The system consists of four identical cylindrical waveguide
      chambers, each with a plastic cage for housing the animal. The chamber is fed by
      circularly polarized radiofrequency power in the 1.9 GHz cellular frequency band
      and is vertically mounted so that the long axis of the animal is co-planar with
      the rotating incident electric field. Power sensors were used along with
      directional or hybrid couplers and a digital voltmeter for data acquisition for
      real-time dose rate monitoring. The system was tested to evaluate its dose rate
      performance when a mouse phantom or a mouse cadaver was inside the cage. The dose
      rate was quantified in terms of whole-body-average (WBA) specific absorption rate
      (SAR) per input power using both measurement and computational methods. The
      exposures of the mouse phantom and cadaver were evaluated for various possible
      postures and positions. The measurement results showed that the highest WBA-SAR
      was 16.9 W kg per 1 W incident power when the cadaver was lying prone against the
      cage wall and the lowest WBA-SAR was 10.4 W kg per 1 W incident power when the
      cadaver was standing upright in the cage center. These results were found to be
      in good agreement with those obtained from the computational method.

PMID- 22850230
TI  - Electron paramagnetic resonance dosimetry for a large-scale radiation incident.
AB  - With possibilities for radiation terrorism and intensified concerns about nuclear
      accidents since the recent Fukushima Daiichi event, the potential exposure of
      large numbers of individuals to radiation that could lead to acute clinical
      effects has become a major concern. For the medical community to cope with such
      an event and avoid overwhelming the medical care system, it is essential to
      identify not only individuals who have received clinically significant exposures
      and need medical intervention but also those who do not need treatment. The
      ability of electron paramagnetic resonance to measure radiation-induced
      paramagnetic species, which persist in certain tissues (e.g., teeth, fingernails,
      toenails, bone, and hair), has led to this technique becoming a prominent method
      for screening significantly exposed individuals. Although the technical
      requirements needed to develop this method for effective application in a
      radiation event are daunting, remarkable progress has been made. In collaboration
      with General Electric and through funding committed by the Biomedical Advanced
      Research and Development Authority, electron paramagnetic resonance tooth
      dosimetry of the upper incisors is being developed to become a Food and Drug
      Administration-approved and manufacturable device designed to carry out triage
      for a threshold dose of 2 Gy. Significant progress has also been made in the
      development of electron paramagnetic resonance nail dosimetry based on
      measurements of nails in situ under point-of-care conditions, and in the near
      future this may become a second field-ready technique. Based on recent progress
      in measurements of nail clippings, it is anticipated that this technique may be
      implementable at remotely located laboratories to provide additional information
      when the measurements of dose on-site need to be supplemented. The authors
      conclude that electron paramagnetic resonance dosimetry is likely to be a useful
      part of triage for a large-scale radiation incident.

PMID- 22850232
TI  - Evaluation of tea as a matrix in a dual (3H/14C) performance testing program in
      Canada.
AB  - Urine is the most popular matrix used in performance testing programs (PTP) and
      inter-comparison programs (ICP) for bioassay. Because it comes from humans, there
      are concerns regarding its biosafety. For large programs, its collection can take
      several hours or days to complete. In addition, natural urine has an unpleasant
      smell, which tends to worsen with increasing storage time. In order to solve some
      of these problems, the Bioassay Section at the Radiation Protection Bureau in
      Health Canada has been investigating the use of tea in both PTP and ICP
      exercises. A method based on diluting tea steeps and scanning them in the UV-VIS
      range of the light spectrum to select appropriate concentrations as simulated
      urine for the programs has been published. So far, however, only single H and
      single C in tea have been studied. The results were found to be compatible and
      very successful under the S-106 standard of the Canadian Nuclear Safety
      Commission. This report is an extension of similar investigations and shows that
      tea samples spiked with both H and C (DUAL) are also compatible and produce
      excellent PTP results.

PMID- 22850233
TI  - Detection efficiency for measuring 241Am in axillary lymph nodes using different
      types and sizes of detectors.
AB  - The detection efficiency and interference susceptibility of four different types
      of low energy photon detectors, each with a unique geometric arrangement, were
      compared for direct measurement of Am deposited in the axillary lymph nodes.
      Although the most efficient detector was a single large 23,226 mm square phoswich
      detector, it was also the most susceptible to confounding depositions from
      activity deposited in adjacent organs. The array of two 2,800 mm high purity
      germanium detectors exhibited the highest efficiency per unit detector area with
      some resistance to confounding from activity deposited in the lungs. The array of
      two 4,560 mm NaI(Tl) detectors was the least susceptible to confounding and
      nearly as efficient per square millimeter as the high purity germanium detector
      array. Thus, selection of a detector system for in vivo measurement of activity
      deposited in the axillary lymph nodes should consider whether there is a
      likelihood for activity deposited in other organs, such as the lungs, skeleton,
      or liver, to create an interference that will confound the measurement result.

PMID- 22850234
TI  - Reevaluation of USTUR plutonium wound case 0262 using Bayesian methodology and
      new data.
AB  - Skin penetration by radionuclide contaminants serves as a route of entry into the
      body and may pose a serious health risk to humans depending on the magnitude of
      intake. The United States Transuranium and Uranium Registry whole body Case 0262
      was involved in a wound intake of plutonium at the Hanford Site. The registrant
      died about 33 years later. Results were initially reported in 2007 regarding the
      deposition and retention of plutonium in various tissues, including the wound
      site. However in 2009, an additional (previously unrecorded) sample of the wound
      tissue was located in the National Human Radiobiological Tissue Repository. The
      new sample was analyzed using inductively coupled plasma-mass spectrometry (ICP
      MS), and the results were used to calibrate the measurement of emitted Pu x-rays
      from the original wound tissue sample made in 2007. In the present study, the
      analysis of Pu absorption rates from the wound and axillary lymph node from the
      initial study is repeated using the additional wound activity data and ICP-MS
      calibration. This new analysis is carried out using the Weighted Likelihood Monte
      Carlo Sampling (WeLMoS) method and code, which applies Bayesian inference to
      calculate the posterior probability distribution of intake and wound absorption
      parameters directly from the observed data and the assumed biokinetic model
      structure. The resulting central estimates of empirical wound absorption
      parameters and their associated uncertainties are here compared with the
      empirical values recommended in NCRP Report No. 156 for plutonium and with the
      maximum likelihood point estimates derived in the initial study from the Case
      0262 data available at the time.

PMID- 22850235
TI  - Validity and use of the UV index: report from the UVI working group, Schloss
      Hohenkammer, Germany, 5-7 December 2011.
AB  - The adequacy of the UV Index (UVI), a simple measure of ambient solar ultraviolet
      (UV) radiation, has been questioned on the basis of recent scientific data on the
      importance of vitamin D for human health, the mutagenic capacity of radiation in
      the UVA wavelength, and limitations in the behavioral impact of the UVI as a
      public awareness tool. A working group convened by ICNIRP and WHO met to assess
      whether modifications of the UVI were warranted and to discuss ways of improving
      its effectiveness as a guide to healthy sun-protective behavior. A UV Index
      greater than 3 was confirmed as indicating ambient UV levels at which harmful sun
      exposure and sunburns could occur and hence as the threshold for promoting
      preventive messages. There is currently insufficient evidence about the
      quantitative relationship of sun exposure, vitamin D, and human health to include
      vitamin D considerations in sun protection recommendations. The role of UVA in
      sunlight-induced dermal immunosuppression and DNA damage was acknowledged, but
      the contribution of UVA to skin carcinogenesis could not be quantified precisely.
      As ambient UVA and UVB levels mostly vary in parallel in real life situations,
      any minor modification of the UVI weighting function with respect to UVA-induced
      skin cancer would not be expected to have a significant impact on the UV Index.
      Though it has been shown that the UV Index can raise awareness of the risk of UV
      radiation to some extent, the UVI does not appear to change attitudes to sun
      protection or behavior in the way it is presently used. Changes in the UVI itself
      were not warranted based on these findings, but rather research testing health
      behavior models, including the roles of self-efficacy and self-affirmation in
      relation to intention to use sun protection among different susceptible groups,
      should be carried out to develop more successful strategies toward improving sun
      protection behavior.

PMID- 22850236
TI  - The Fukushima nuclear crisis reemphasizes the need for improved risk
      communication and better use of social media.
AB  - The potential of social media has expanded far beyond the initial function of
      social communication among a network of friends. It has become an increasingly
      important tool in risk communication to allow the dissemination of timely and
      accurate information to global citizens to make more informed choices regarding a
      particular crisis. The Fukushima nuclear crisis is an example where the potential
      of social media was not fully tapped. This caused undue stress and distrust of
      authorities. While the use of social media in this crisis could have altered
      significantly the level of trust in authorities and others, two additional points
      should be considered. One point is the use of plain language versus scientific
      language in order to reach a wider audience. The other is an urgent need to
      improve public information especially in the event of a nuclear emergency and to
      enhance educational efforts and action by improving radiological protection
      communication from regulatory bodies and international agencies. These are points
      that also play a large role in the use of social media.

PMID- 22850237
TI  - An assessment of radon in groundwater in New York state.
AB  - A set of 317 samples collected from wells throughout New York State (excluding
      Long Island) from 2003 through 2008 was used to assess the distribution of radon
      gas in drinking water. Previous studies have documented high concentrations of
      radon in groundwater from granitic and metamorphic bedrock, but there have been
      only limited characterizations of radon in water from sedimentary rock and
      unconsolidated sand-and-gravel deposits in New York. Approximately 8% of the
      samples from bedrock wells exceed 89 Bq L (eight times the proposed regulatory
      limit), but only 2% of samples from sand-and-gravel wells exceed 44 Bq L.
      Specific metamorphic and sedimentary rock formations in New York are associated
      with the high radon concentrations, indicating that specific areas of New York
      could be targeted with efforts to reduce the risk of exposure to radon in
      groundwater. Additionally, radon in groundwater from the sand-and-gravel aquifers
      was found to be directly correlated to radon in indoor air when assessed by
      county.

PMID- 22850238
TI  - Swiss population exposure to radiation by interventional radiology in 2008.
AB  - The aim of this study was to investigate the radiation exposure of the Swiss
      population to interventional procedures. A nationwide survey was conducted in
      Switzerland. The annual effective dose per capita due to interventional
      procedures was found to be 0.14 mSv, corresponding to 12% of the total dose.
      Coronary angiography and percutaneous coronary interventions were found to be the
      most frequent and the most irradiating interventional procedures, accounting for
      52% of the total examination frequency and 64% of the dose delivered to the
      population. Switzerland stands at the same level as other countries in terms of
      effective dose per capita due to interventional radiology.

PMID- 22850239
TI  - Photon interaction parameters of dosimetric interest in bone.
AB  - The effective atomic numbers (Z(eff)) and electron densities (N(el)) of cortical
      and compact bone have been computed for total and partial photon interactions
      (photoelectric absorption, coherent scattering, incoherent scattering, pair
      production in a nuclear field, pair production in an electronic field, and sum of
      non-coherent scattering) by computing the molecular, atomic, and electronic cross
      section in the wide energy range of 1 keV-100 GeV using WinXCom. The variations
      of effective atomic number and electron density with energy are shown graphically
      for all photon interactions. The effective atomic numbers (ZPEA(eff)) for photon
      energy absorption are also calculated from mass energy absorption coefficients in
      the energy range 1 keV-20 MeV. The kerma values of bone relative to air are also
      computed. Additionally, computed tomography (CT) numbers of bone for photon
      interaction and energy absorption are also computed. The computed Z(eff) and
      N(el) may be useful in choosing a substitute composite material in place of bone.
      The estimated mass energy absorption coefficient may be used to evaluate dose and
      determine the surviving fraction (S) for bone. The usefulness of computed data in
      the simulation of tissue substitutes is also discussed.

PMID- 22850241
TI  - Health Physics Society Prospectus.

PMID- 22850243
TI  - The first aptamer-apheresis column specifically for clearing blood of beta1
      receptor autoantibodies.
AB  - BACKGROUND: Application of immunoapheresis to eliminate pathogenic autoantibodies
      targeting the second extracellular loop of the beta1-receptor (beta1-AABs) is
      currently investigated in patients with cardiomyopathy. Aptamers (single short
      DNA or RNA strands) are a new class of molecules that bind to a specific target
      molecule. This property qualifies aptamers for potential use in the apheresis
      technique. We recently identified an aptamer that specifically binds to beta1
      AABs, so in the present study we tested whether this aptamer could be used as a
      binder to prepare an apheresis column suitable for clearing beta1-AABs from rat's
      blood. METHODS AND RESULTS:  An apheresis column was designed containing the
      beta1-AAB-targeting-aptamer coupled to sepharose. As tested in vitro, this column
      (1) binds beta1-AABs highly specifically without marked interference with common
      IgGs, (2) has a capacity for clearing of approximately 1L of beta1-AAB-positive
      serum and (3) can be completely regenerated for subsequent use. Using the column
      for extracorporeal apheresis of spontaneously hypertensive rats (SHR) positive
      for both beta1-AABs and muscarinic 2-receptor autoantibodies (M2-AABs), only
      beta1-AABs were removed. In a follow-up of 9 weeks, recurrence of beta1-AABs in
      the blood of SHR could not be detected. CONCLUSIONS:  For the first time, a newly
      designed apheresis column with a beta1-AAB specific aptamer as a binder was
      successfully used to eliminate beta1-AABs from SHR blood. 

PMID- 22850244
TI  - Complex biphasic relationship between epicardial fat and ischemic heart disease.

PMID- 22850245
TI  - The use of the model species Arabidopsis halleri towards phytoextraction of
      cadmium polluted soils.
AB  - Phytoremediation consists in treating environmental pollutions through the use of
      plants and their associated microbes. Phytoremediation can be used for pollutant
      stabilization, extraction, degradation or volatilization. Cadmium is one of the
      most toxic trace metallic elements for living organisms and its accumulation in
      the environment is recognized as a worldwide concern. Plants suitable for
      efficient pollutant extraction from the soil should combine different
      characteristics like fast growth, high biomass, high tolerance and high
      accumulation capacities in harvestable parts. A rare class of plants called
      hyperaccumulators combines extremely high tolerance degrees and foliar
      accumulation of trace elements. With regard to cadmium, none of the Cd
      hyperaccumulators identified has met the criteria for efficient phytoextraction
      so far. By virtue of genetic engineering it is possible to transfer genes
      involved in Cd tolerance or accumulation in high biomass plants. Nevertheless,
      the genetic determinants of Cd hyperaccumulation are far from being understood.
      It is thus indispensable to acquire more knowledge about these processes. Among
      Cd hyperaccumulators, Arabidopsis halleri (some populations can hyperaccumulate
      Cd) is considered as a model species for the study of metal homeostasis and
      detoxification. This review will summarize our knowledge about Cd tolerance and
      accumulation acquired in A. halleri and how this knowledge may be used in
      phytoextraction.

PMID- 22850246
TI  - Cortical electrical stimulation with varied low frequencies promotes functional
      recovery and brain remodeling in a rat model of ischemia.
AB  - In this study, we investigated whether fully implantable CES with low current
      density and varying low-frequency burst impulse train enhances functional
      recovery and promotes brain remodeling in both the ipsilesional and
      contralesional cortex. Adult rats received occlusion of the right middle cerebral
      artery for 120min. One week after ischemia, electrodes were implanted to rats
      with CES lasting 2 weeks followed by 4-week observation period. After 2-week
      stimulation and 4-week observation period, body weight (BW) of the rats in CES
      group was higher than that in no stimulation (NS) group. Limb placement test,
      foot-fault test and beam walking test demonstrate that CES significantly enhanced
      functional recovery. Immunohistochemical study has shown that CES enhanced
      angiogenesis and dendritic sprouting, and suppressed inflammatory response in the
      ischemic cortex. CES also promoted dendritic sprouting and suppressed
      inflammatory response in the contralesional cortex. These results suggest the
      stimulation protocol is safe, and greatly improves functional recovery and brain
      remodeling in the 4 weeks following 2 weeks stimulation.

PMID- 22850248
TI  - Tympanometry in general practice: use, problems and solutions.
AB  - OBJECTIVES: The diagnosis in children with middle ear symptoms is often
      difficult. Tympanometry is recommended as a supplementary diagnostic tool with a
      high predictive value for fluid or no fluid in the middle ear. The aim of this
      study was to examine how tympanometry was used in Danish general practice in
      2009, to report common problems general practitioners (GPs) and GP nurses
      encounter in tympanometry and to evaluate the effect of a practical and
      theoretical course. METHODS: A 1-year registration of the use of tympanometry in
      the Danish National Health Service Register in two regions with 40% of all Danish
      GPs and a survey among 197 participants in a course on diagnosis of otitis media
      and tympanometry in children were used. The Danish National Health Insurance
      covers 100% of GPs because they administer reimbursement for their activities,
      including tympanometry. RESULTS: During the year 2009, 1433 GPs in 702 clinics
      were on the list. A total of 417 clinics performed 35 529 tympanometries. Some
      285 clinics (40.6%) did not perform tympanometry in 2009. The active clinics
      performed 42 tympanometries per GP. A 1-day course improved the knowledge and
      practical skills of the participating GPs and nurses. A majority (70%) stated in
      a self-reported questionnaire that tympanometry often provided important
      information, especially about middle ear fluid, and 48% reported that
      tympanometry several times during the past 2 weeks had changed their management
      of a middle ear problem. Few had not used their tympanometer during the 2 weeks
      preceding the survey. The response rate was 72%. CONCLUSIONS: The use of
      tympanometry is very skewed. A 6-hour course could improve GPs' care of patients
      with middle ear problems by using tympanometry.

PMID- 22850247
TI  - Robust behavioral effects of song playback in the absence of testosterone or
      corticosterone release.
AB  - Some species of songbirds elevate testosterone in response to territorial
      intrusions while others do not. The search for a general explanation for this
      interspecific variation in hormonal response to social challenges has been
      impeded by methodological differences among studies. We asked whether song
      playback alone is sufficient to bring about elevation in testosterone or
      corticosterone in the dark-eyed junco (Junco hyemalis), a species that has
      previously demonstrated significant testosterone elevation in response to a
      simulated territorial intrusion when song was accompanied by a live decoy. We
      studied two populations of juncos that differ in length of breeding season (6-8
      vs. 14-16 weeks), and conducted playbacks of high amplitude, long-range song. In
      one population, we also played low amplitude, short-range song, a highly potent
      elicitor of aggression in juncos and many songbirds. We observed strong
      aggressive responses to both types of song, but no detectable elevation of plasma
      testosterone or corticosterone in either population. We also measured rise in
      corticosterone in response to handling post-playback, and found full capacity to
      elevate corticosterone but no effect of song class (long-range or short-range) on
      elevation. Collectively, our data suggest that males can mount an aggressive
      response to playback without a change in testosterone or corticosterone, despite
      the ability to alter these hormones during other types of social interactions. We
      discuss the observed decoupling of circulating hormones and aggression in
      relation to mechanisms of behavior and the cues that may activate the HPA and HPG
      axes.

PMID- 22850249
TI  - Patients' views about the use of their personal information from general practice
      medical records in health research: a qualitative study in Ireland.
AB  - BACKGROUND: National policies are being developed, which may limit access to
      patients' records for health research. This could reduce the ability of health
      research to benefit society as a whole. It is important to develop an in-depth
      understanding of people's views across demographic groups to inform such policy
      development.  Aims. To explore patients' views about the use of their general
      practice records in health research with attention to gender and age.  Design of
      study. Qualitative study using focus groups. SETTING: Six General Practices in
      the west of Ireland. METHOD: Focus Group interviews with 35 people who were
      patients at the practices. RESULTS: Overall, participants were positively
      inclined towards the idea of information from their records (anonymous and
      identifiable) being used in research for the 'greater good' although there were
      some concerns about personal information being 'leaked'. Males emphasized risks
      in relation to employment and finances, whereas females emphasized risks in
      relation to social discomfort and embarrassment. Participants were supportive of
      consent models that enable patients to give prior ongoing consent for specific
      agreed 'levels' of data use, affording patients self-determination without the
      need for consent request on study-by-study basis. CONCLUSION: Overall male and
      female patients of different ages are supportive of the use of their general
      practice records in health research and of general practitioners as data
      protectors.

PMID- 22850250
TI  - Toll-Like Receptor 4 (TLR4) expression and stimulation in a model of
      intervertebral disc inflammation and degeneration.
AB  - STUDY DESIGN: We measured the expression and responses of Toll-Like Receptor 4
      (TLR4) activation in the intervertebral disc (IVD) in vitro and in vivo. We
      hypothesize that stimulation of the IVD with the TLR4 ligand lipopolysaccharide
      (LPS) results in upregulation of a coordinated set of proinflammatory mediators
      and inhibition of matrix expression, both consistent with a molecular profile of
      degeneration. OBJECTIVE: To characterize early inflammatory and morphological
      changes induced by TLR4 activation in the IVD. SUMMARY OF BACKGROUND DATA: TLR4
      is a pattern recognition receptor activated in innate immunity that has been
      implicated in disease mechanisms of inflammatory cartilaginous degeneration.
      However, no study to date has examined the expression and responses of TLR4 in
      the IVD. METHODS: IVD cells were stimulated with LPS in a dose-dependent manner,
      and inflammatory cytokine levels were measured by quantitative reverse
      transcription-polymerase chain reaction. Histological and inflammatory changes
      due to in vivo injection of LPS into the rat caudal IVD were measured by enzyme
      linked immunosorbent assay and immunoblotting. RESULTS: Baseline TLR4 expression
      in IVD tissue varied according to cell type. LPS stimulation resulted in
      significant increases in tumor necrosis factor alpha (TNF)-alpha, interleukin
      (IL)-1beta, IL-6, and nitric oxide levels and significant inhibition in aggrecan
      and collagen-2. Intradiscal injection of LPS was found to cause moderate
      degenerative changes in the IVD, with increases in tissue levels of IL-1beta, TNF
      alpha, high mobility group box 1 protein (HMGB1), and macrophage migration
      inhibitory factor (MIF). CONCLUSION: This study provides the first evidence that
      IVD cells express TLR4 and are responsive to TLR4 activation by upregulating a
      coordinated set of inflammatory cytokines. This study suggests that intradiscal
      injection of LPS offers a model for triggering inflammation of the IVD,
      demonstrating that inflammatory insults alone may potentially trigger
      degenerative changes of the IVD.

PMID- 22850251
TI  - Small molecules that regulate zymosan phagocytosis of macrophage through
      deactivation of Rho GTPases.
AB  - Phagocytosis and subsequent degradation of pathogens by macrophages play a
      pivotal role in host innate immune response to microbial infections. To find
      small molecule regulators for the investigation of complicated phagocytic
      process, we screened our in-house chemical library and found chemicals which
      inhibit phagocytosis of zymosan by macrophages. A representative compound 5a
      reduced phagocytosis of zymosan in both peritoneal macrophages and RAW264.7 cells
      in a dose-dependent manner. Treatment of 5a led to downregulate the key
      regulators of phagocytosis, Rac1, Rac2 and Cdc42, and slightly reduced
      phosphorylation of Akt by zymosan.

PMID- 22850253
TI  - Symptoms of heart disease or its treatment may increase Beck Depression Inventory
      Scores in hospitalized post-myocardial infarction patients.
AB  - OBJECTIVE: The Beck Depression Inventory (BDI) is one of the most commonly used
      self-report depression symptom questionnaires in medical settings. The revised
      BDI-II was developed in 1996, partially due to concerns about the influence of
      somatic symptoms from medical illness on BDI scores. The BDI, however, continues
      to be frequently used in medical settings. The objective of this study was to
      examine the degree to which somatic symptom items influence BDI scores among
      hospitalized post-myocardial infarction (MI) patients with major depressive
      disorder (MDD) compared to psychiatry outpatients with MDD matched on
      cognitive/affective scores, sex, and age. METHODS: Somatic scores of post-MI
      patients with MDD and matched psychiatry outpatients with MDD were compared using
      independent samples t-tests. RESULTS: A total of 579 post-MI patients with MDD
      (mean age=54.4 years, SD=9.9) and 579 psychiatry outpatients with MDD (mean
      age=51.2 years, SD=9.7) were matched on cognitive/affective scores, sex, and age.
      Somatic symptoms accounted for 47% of BDI total scores among post-MI patients
      (mean total=22.6, SD=8.8) versus 37% among psychiatry outpatients (mean
      total=19.2, SD=9.7). Somatic scores of post-MI patients were 3.4 points higher
      than for matched psychiatry outpatients (95% confidence interval 3.0 to 3.9;
      p<.001), a difference that is equivalent to 15% of total post-MI patient scores.
      CONCLUSION: BDI scores of hospitalized post-MI patients with MDD may, in part,
      reflect symptoms of the acute medical condition or its treatment, rather than
      depression. The BDI-II was designed to reduce the influence of somatic symptoms
      on total scores and may be preferable to the 'BDI among heart disease patients.

PMID- 22850254
TI  - The PHQ-9 versus the PHQ-8--is item 9 useful for assessing suicide risk in
      coronary artery disease patients? Data from the Heart and Soul Study.
AB  - OBJECTIVE: Item 9 of the Patient Health Questionnaire-9 (PHQ-9), which inquires
      about both passive thoughts of death and active ideas of self-harm, has been used
      to assess suicide risk. The objectives of this study were (1) to determine the
      proportion of patients who responded "yes" to Item 9 who endorsed active suicidal
      ideation in response to more direct questions from a structured clinical
      interview and (2) to compare the sensitivity and specificity for detecting cases
      of depression of the PHQ-9 and the PHQ-8, which does not include Item 9, as well
      as the correlation between the PHQ-8 and PHQ-9. METHODS: Coronary artery disease
      (CAD) outpatients were administered the PHQ-9 and the Computerized Diagnostic
      Interview Schedule (C-DIS). Item 9 responses were compared to suicidal ideation
      and intent in the last year based on the C-DIS. Scores on the PHQ-8 were obtained
      by eliminating Item 9 from the PHQ-9. Test characteristics of the PHQ-9 and PHQ-8
      were compared. RESULTS: Of 1022 patients, 110 (10.8%) endorsed Item 9. Of those,
      only 22 (19.8%) reported thoughts about committing suicide, and only 9 of those
      (8.1%) reported a suicide plan any time in the last year based on the C-DIS.
      Correlation between PHQ-9 and PHQ-8 scores was r=0.997. Sensitivity and
      specificity for the PHQ-9 (54%, 90%) and PHQ-8 (50%, 91%) to detect major
      depression were similar. CONCLUSION: Item 9 does not appear to be an accurate
      suicide screen. The PHQ-8 may be a better option than the PHQ-9 in CAD patients.

PMID- 22850252
TI  - Bidirectional alloreactivity: A proposed microchimerism-based solution to the
      NIMA paradox.
AB  - The NIMA paradox is the observation that in transplants of allogeneic kidneys or
      hematopoietic stem cells, siblings benefit from re-exposure to non-inherited
      maternal antigens (NIMA), whereas re-exposure to a transplant from mother
      herself, theoretically the ideal "NIMA" donor, does not yield clinical results
      superior to a father-donated allograft. Recent observations of bidirectional
      alloreactivity in kidney and cord blood transplantation offer a possible solution
      to this paradox. If correct, the proposed solution points the way to clinical
      applications of microchimerism in solid organ and hematopoetic transplants.

PMID- 22850255
TI  - Increased risk of hypertension in patients with major depressive disorder: a
      population-based study.
AB  - OBJECTIVE: We conducted this study to detect the prevalence, incidence, and risk
      factors of hypertension in Taiwanese patients with major depressive disorder
      (MDD). METHODS: The National Health Research Institute provided a database of
      1,000,000 random subjects for study. We obtained a random sample of 766,427
      subjects, aged >=18 years in 2005. Study subjects had at least one service claim
      during 2005 for either outpatient or inpatient care with a primary diagnosis of
      MDD or with a primary or secondary diagnosis of hypertension and combined with
      antihypertensive drug treatment were identified. We also compared the incidence
      of hypertension among patients with MDD and the general population from 2006
      through 2008. RESULTS: The 1-year prevalence of hypertension in patients with MDD
      was higher than that in the general population (21.21% vs. 13.28%, risk ratio,
      1.22; 95% confidence interval, 1.17-1.28). Compared with the general population,
      patients with MDD had a higher prevalence of hypertension in all age, sex,
      insurance amount, region, and urbanicity groups. The average annual incidence of
      hypertension in patients with MDD from 2006 to 2008 was higher than that in the
      general population (3.96% vs. 2.90%, risk ratio, 1.19; 95% confidence interval,
      1.08-1.31). Compared with the general population, patients with MDD had a higher
      incidence of hypertension in all age, and male groups. CONCLUSIONS: Patients with
      MDD had a higher prevalence and a higher incidence of hypertension than that in
      the general population. Age, male gender, and antipsychotic use were risk factors
      for hypertension among patients with MDD.

PMID- 22850257
TI  - Contributions of diabetic macro-vascular complications and hip fracture to
      depression onset in elderly patients with diabetes: an 8-year population-based
      follow-up study.
AB  - OBJECTIVE: To prospectively examine the roles of diabetic macro-vascular
      complications and hip fracture in association with depression onset in Taiwan's
      elderly diabetic population. METHODS: A representative sample of elderly diabetic
      patients (n=144,216) identified in 2000 were linked to National Health Insurance
      claims (2000-2007) to ascertain the diagnoses of depression in both outpatient
      and inpatient settings. The person-year approach with Poisson assumption was used
      to estimate the hazard rates. Using Cox proportional hazard regression model, we
      evaluated the relative risk of depression in relation to diabetic macro-vascular
      complications and hip fracture. The additive effects from the above medical
      conditions were also assessed. RESULTS: The 8-year cumulative risk of depression
      was 5.08%, representing an incidence density of 8.40 per 1000 patient-years.
      Hazard ratio (HR) with 95% confidence interval (CI) for the elderly diabetes
      associated with cardiovascular disease (CVD), hip fracture, and lower extremity
      amputation was 1.13 (1.04-1.23), 1.10 (0.91-1.34), and 1.25 (0.95-1.65),
      respectively. Additionally, we found that the more the complications or hip
      fracture, the higher the risk of depression onset in elderly diabetes.
      CONCLUSION: The increased number of diabetic macro-vascular complications and hip
      fracture is significantly associated with a higher risk of depression onset in
      elderly diabetes. Future studies should be conducted to assess the feasibility
      and cost-effectiveness of intensive depression screening program in elderly
      diabetes suffering from macro-vascular complications and hip fracture.

PMID- 22850256
TI  - Evidence for accelerated vascular aging in bipolar disorder.
AB  - OBJECTIVE: Persons with bipolar disorder face excess risk of cardiovascular
      disease, although the biobehavioral mechanisms and time course are unclear. We
      measured vascular stiffness in a cross-sectional sample of participants with
      bipolar disorder and compared results to published normative data to assess time
      course and relationship to behavioral risk factors. METHODS: 62 individuals with
      bipolar disorder (33+/-6.7years; 64% female) underwent non-invasive assessment of
      arterial stiffness through arterial applanation tonometry. Lifetime tobacco
      exposure was estimated on clinical interview. Physical activity was assessed
      using the long-version of the International Physical Activity Questionnaire
      (IPAQ). A food frequency questionnaire was used to compute Alternate Healthy
      Eating Index (AHEI), a measure of overall dietary quality. Medication histories
      were systematically abstracted from pharmacy records. RESULTS: Participants over
      the age of 32 (median split) had greater arterial stiffness than expected from
      age-based population norms for pulse wave velocity (PWV) (7.6 vs. 7.0m/s, p=.02)
      and estimated aortic augmentation pressure (AIx) (14.2 vs. 8.2%, p=.0002). The
      younger portion of the sample did not differ from population norms on these
      measures (PWV 6.3 vs. 6.4m/s, p=.45 and AIx 7.6 vs. 7.4%, p=.60). In the older
      half of the sample, physical activity was inversely associated with AIx and
      poorer diet marginally associated with PWV. These findings were independent of
      body mass index (BMI), which was strongly related to arterial stiffness.
      CONCLUSION: Risk for vascular disease may be acquired over the long-term course
      of affective illness. This risk appears to reflect maladaptive health behaviors,
      which may be amenable to intervention.

PMID- 22850258
TI  - PTSD and depression as predictors of physical health-related quality of life in
      tobacco-dependent veterans.
AB  - OBJECTIVE: Smoking, depression and PTSD are related to poor physical health
      outcomes and health-related quality of life (HRQoL). Previous studies examining
      the effects of quitting smoking on HRQoL have been mixed. This study aimed to
      examine the effects of PTSD, depressive symptoms and smoking cessation on HRQoL
      in a sample receiving treatment for PTSD. METHOD: This study utilized archival
      interview and self-report data from a clinical trial (VA Cooperative Study 519)
      that recruited tobacco dependent veterans with chronic PTSD (N=943). RESULTS:
      Analyses were conducted using hierarchical linear modeling and indicated that
      PTSD and depressive symptoms differentially affected the various physical health
      status domains. Additionally, quitting smoking was associated with better self
      perceived health status and social functioning. CONCLUSION: Our findings further
      explain the interrelationships of PTSD, depression, and smoking in the prediction
      of physical HRQoL and advocate the importance of integrated care.

PMID- 22850259
TI  - Course and predictors of posttraumatic stress among male train drivers after the
      experience of 'person under the train' incidents.
AB  - OBJECTIVE: The present prospective study aimed to identify the frequency and
      course of posttraumatic stress symptoms, anxiety, depression, and quality of life
      in train drivers after the experience of 'person under the train' incidents.
      Furthermore, associations between predictors of posttraumatic stress stratified
      by pre-, peri- and posttraumatic factors, psychological distress, quality of life
      (QoL), sense of coherence, lack of meaning in life, and post-trauma thoughts are
      analyzed. METHODS: Patients (100% male, mean age 48 years) were assessed at the
      beginning (n=73), at the end (n=71) and six months (n=49) after a four-week
      rehabilitation program and completed validated self-report questionnaires (e.g.
      Posttraumatic Diagnostic Scale, Hospital Anxiety and Depression Scale, Short-Form
      Health Survey). RESULTS: Train drivers experienced averagely 1.8 'person under
      the train' incidents (range 1-8); the majority (81%) was involved in a railway
      suicide. At the beginning of the rehabilitation, 44% of the patients were
      classified as having moderate to severe PTSD, and 14% as having severe PTSD.
      Posttraumatic stress decreased significantly over time (p=.003, eta2=.17). We
      found no significant differences in the course of posttraumatic stress, anxiety,
      depression, distress and QoL between patients who experienced one or more than
      one railway related accident or suicide. Anxiety, sense of guilt and sense of
      alienation emerged as the most important factors in predicting posttraumatic
      stress six months after rehabilitation (R2=0.55). CONCLUSION: Findings emphasize
      the importance of rehabilitation programs for train drivers after railway-related
      incidents. However, research is needed to develop effective rehabilitation
      interventions particularly tailored to this patient group.

PMID- 22850260
TI  - Statistical methods in randomised controlled trials for delirium.
AB  - OBJECTIVE: The analysis of clinical trials in delirium is typically complicated
      by treatment dropouts and by the fact that even untreated individuals may have a
      good prognosis. These features of delirium trials warrant special statistical
      attention; implications for each stage of a trial planning process are described.
      METHODS: Choice of outcome, patient sample, and data collection in delirium
      trials are discussed. Descriptions are given, together with examples, of time-to
      event, imputation-based, linear and nonlinear models for the analysis of
      randomised controlled trials for delirium. RESULTS: Imputation allows evaluation
      of the plausibility of individual recovery trajectories, but some simple
      imputations are found to be unsuitable for delirium research. Time-to-event and
      nonlinear models encourage a global perspective on analysis, which is often
      preferable to cross-sectional end-of-trial assessments. It is suggested that
      nonlinear random effects models for longitudinal trajectories are particularly
      suitable in a delirium context. CONCLUSION: It is hoped that the methods
      described, and nonlinear models in particular, will play a part in convincing
      analyses of future delirium research.

PMID- 22850261
TI  - Fatigue and tiredness in people with spinal cord injury.
AB  - OBJECTIVE: Fatigue is a common symptom in people with neurological injury such as
      spinal cord injury (SCI), though its nature and occurrence in people with SCI are
      not well understood. The objective of this research was to investigate fatigue
      and its relationship to factors such as mood states and self efficacy in adult
      people with SCI compared to able-bodied controls. METHODS: Participants included
      41 adults with SCI living in the community and 41 able-bodied controls matched
      for age and sex ratios and education. All participants first completed a
      comprehensive psychological assessment and were then asked to take part in a 2-3
      hour session composed of a regimen of cognitive tasks that required constant
      concentration and attention. Participants were assessed after completing this
      task. RESULTS: The SCI group was found to have significantly elevated levels of
      fatigue, as well as elevated depressive mood, anxiety and poor self-efficacy. The
      SCI group was also found to suffer excessive levels of tiredness as a consequence
      of the 2-3 hour task. Factors such as depressive mood and poor self-efficacy were
      shown to increase the risk of excessive tiredness. CONCLUSION: People with a
      neurological injury such as SCI have a high risk of having fatigue and are
      susceptible to experiencing excessive tiredness when performing extended tasks,
      and the presence of elevated depressive mood or poor expectations towards self
      management will increase this susceptibility. Implications for managing fatigue
      and improving social access in SCI populations are discussed.

PMID- 22850262
TI  - The effect of multimorbidity on health related functioning: temporary or
      persistent? Results from a longitudinal cohort study.
AB  - OBJECTIVE: Multimorbidity is known for its negative effects on health related
      functioning. It remains unclear if these effects are stable over time. The aim
      was to investigate if the relation between single morbidity/multimorbidity and
      health related functioning is temporary or persistent. METHODS: Data were
      collected as part of the Maastricht Aging Study (MAAS), a prospective study into
      the determinants of cognitive aging. Participants (n=1184), 24-81 years old, were
      recruited from a patient database in primary care (Registration Network Family
      Practices). Morbidity status (i.e. healthy, single morbidity or multimorbidity)
      and the Short Form Health Survey (SF-36) were both assessed at baseline, at 3-
      and 6-year follow-up. RESULTS: At baseline but not at 3- and 6-year follow-up,
      participants with single morbidity reported poorer physical functioning than
      their healthy counterparts. Multimorbidity was associated with poorer physical
      functioning at all measurements. Participants with multimorbidity showed a steep
      decrease in physical functioning between 3- and 6-year follow-up. Multimorbidity
      appeared to be unrelated to mental functioning. At baseline and at 3-year follow
      up, participants who had a change in morbidity status reported poorer physical
      functioning than their healthy counterparts. CONCLUSIONS: Poorer physical
      functioning that accompanies multimorbidity is persistent and may even increase
      over time. People, who acquire one or more diseases during the 3-year follow-up,
      already showed poorer physical functioning at baseline compared to people who
      remained healthy during these years. Post-hoc analyses, using the SCL-90 as an
      outcome measure, did show that multimorbidity was related to depressive and
      anxiety complaints. However, these complaints seem to decline over time.

PMID- 22850263
TI  - Predictors of mental and physical health in non-cirrhotic patients with viral
      hepatitis: a case control study.
AB  - OBJECTIVE: To identify independent predictors of mental and physical health in
      patients with viral hepatitis. METHODS: Hepatitis C (HCV) and hepatitis B (HBV)
      infected patients, and community control subjects with equal age and sex
      distribution were recruited. All subjects filled in personal characteristics
      questionnaire, Hospital Anxiety and Depression Scale (HADS), Iowa Fatigue Scale
      (IFS), and Medical Outcomes Survey Short Form-12 (SF-12). All patients had
      measurement of routine laboratory values, and some had recent liver biopsy.
      Regression analyses were used to identify predictors of physical and mental
      health. RESULTS: One hundred eighty nine subjects (162 males, 27 females, for
      each group N=63) with mean (+/-SD) age of 39+/-11years were included. Anxiety and
      depression were important predictors of SF-12 (and its subscales MCS and PCS) and
      IFS scores, whereas IFS scores independently predicted HADS, PCS, MCS, and SF-12
      scores. After controlling for confounders, HCV infection was independently
      associated with impairment of physical health. Moreover, creatinine showed an
      inverse strong relation with fatigue. Genotype 3a of HCV was independently
      associated with depressed and anxious states, whereas higher inflammation grade
      was significantly related to depression. Marital status, non-psychiatric
      comorbidities, and history of alcohol abuse also predicted health scores in the
      patients. Adjusted R(2)s for linear models were 0.571 to 0.709, whereas areas
      under the receiver operating characteristic (ROC) curve for logistic models were
      0.90 to 0.93. CONCLUSION: In viral hepatitis patients, besides mental and medical
      comorbidities, marital status, and alcohol abuse, HCV infection itself is
      associated with impaired physical and possibly mental health.

PMID- 22850264
TI  - Poor self-rated health is significantly associated with elevated C-reactive
      protein levels in women, but not in men, in the Japanese general population.
AB  - OBJECTIVE: Self-rated health (SRH) is associated with risk for mortality, but its
      biological basis is poorly understood. We examined the association between SRH
      and low-grade inflammation in a Japanese general population. METHODS: A total of
      5142 men and 11,114 women aged 40 to 69years were enrolled. SRH was assessed by a
      single question and classified into four categories: good, rather good, neither
      good nor poor, and poor. Serum high-sensitivity C-reactive protein (hsCRP) levels
      were measured by the latex-enhanced immunonephelometric method. Elevated CRP was
      defined as hsCRP level of 1.0mg/L or higher. The association between SRH and
      elevated CRP was evaluated by using logistic regression with adjustment for age,
      socioeconomic status (job status, education and marital status), health-related
      behaviors (smoking status, drinking status, exercise habits and sleep duration),
      and cardiovascular risk factors (body mass index, systolic blood pressure, total-
      and HDL-cholesterol, HbA1c and prevalent stroke and/or myocardial infarction).
      RESULTS: Compared to persons with good SRH, persons with poor SRH had
      significantly higher risk for elevated CRP: age-adjusted ORs (95% CIs) were 1.33
      (1.01-1.76) in men and 1.66 (1.36-2.02) in women. The significant association
      remained even after adjustment for socioeconomic status, health-related behaviors
      and cardiovascular risk factors in women, whereas the significance disappeared in
      men. CONCLUSION: Poor SRH is associated with low-grade inflammation in both
      sexes. In women, but not in men, the association is independent of potential
      confounders. These findings provide an insight into the biological background of
      SRH in a general population.

PMID- 22850265
TI  - The association between Type D personality and illness perceptions in colorectal
      cancer survivors: a study from the population-based PROFILES registry.
AB  - OBJECTIVE: To examine the association between Type D personality and illness
      perceptions among colorectal cancer survivors 1-10years post-diagnosis. METHODS:
      Data from two population-based surveys on colorectal cancer survivors was used.
      Patients diagnosed between 1998 and 2009, as registered in the Eindhoven Cancer
      Registry, received a questionnaire on Type D personality (DS14) and illness
      perceptions (B-IPQ); 81% (n=3977) responded. RESULTS: 750 (19%) patients had a
      Type D personality. They believe their illness has significantly more serious
      consequences, will last significantly longer, and experience significantly more
      symptoms that they attribute to their illness. Also, they are more concerned
      about their illness, and their disease more often influences them emotionally.
      Differences regarding 'consequences', 'concern' and 'emotional response' were
      also clinically relevant. The majority of patients stated that the cause of their
      disease was unknown (23.3%), hereditary (20.3%), lifestyle (15.1%), psychological
      distress (11.9%) or other (11.6%). Significant differences in perceptions on
      cause of disease between Type Ds and non-Type Ds were found for psychological
      distress (16.2 vs. 10.9%; p<0.01), randomness (1.7 vs. 5.3%; p<0.01) and unknown
      (18.8 vs. 24.4%; p<0.01). Multivariate analyses showed that Type D was negatively
      associated with 'coherence' and positively with 'consequences', 'timeline',
      'identity', 'concern', and 'emotional representation'. CONCLUSIONS: These results
      elucidate the associations between personality and illness perceptions,
      demonstrating their close interrelatedness. Our study may be helpful in further
      developing theoretical models regarding giving meaning to illness and the illness
      perceptions that the illness elicits. Future studies should investigate whether
      interventions can positively impact illness perceptions of Type D cancer
      patients.

PMID- 22850266
TI  - Re: Leisure activities and cognitive function in elderly community-dwelling
      individuals in Japan: A 5-year prospective cohort study. Hajime Iwasa, Yuko
      Yoshida, Ichiro Kai, Takao Suzuki, Hunkyung Kim, Hideyo Yoshida. Journal of
      Psychosomatic Research 72 (2012) 159-164.

PMID- 22850268
TI  - The efficacy and safety of 12 weeks of treatment with sertindole or olanzapine in
      patients with chronic schizophrenia who did not respond successfully to their
      previous treatments:  a randomized, double-blind, parallel-group, flexible-dose
      study.
AB  - The aim of this study was to evaluate the efficacy, safety, and tolerability of
      sertindole in comparison with olanzapine in patients with chronic schizophrenia
      who did not respond successfully to their previous treatments. Patients with
      schizophrenia who were at least moderately ill and had failed to respond to
      previous antipsychotic treatment were randomized to double-blind sertindole or
      olanzapine treatment. A total of 389 patients were treated, 196 with sertindole
      (mean dose=17 mg/day) and 193 with olanzapine (mean dose=16 mg/day). Both drugs
      improved all the efficacy scale scores including the Positive and Negative
      Syndrome Scale total score. Although sertindole failed to prove noninferiority to
      olanzapine in terms of reduction in PANSS total score with the last-observation
      carried-forward analysis, this can be attributed to the higher withdrawal rate in
      the sertindole group by day 16 by which sertindole was up-titrated to the
      effective dose. On excluding early withdrawals, the noninferiority criterion was
      fulfilled, as also in the observed-case analysis. They had similar safety
      profiles with respect to the total incidence of adverse events. The incidence of
      asymptomatic QT prolongation was higher in the sertindole group. Sertindole has
      an efficacy and safety profile that is comparable to that of olanzapine. The slow
      titration schedule and lack of sedating effect of sertindole should be considered
      when initiating treatment with this drug.

PMID- 22850269
TI  - Organ-specific proteomics analysis for identification of response mechanism in
      soybean seedlings under flooding stress.
AB  - Flooding is one of the severe environmental factors which impair growth and yield
      in soybean plant. To investigate the organ specific response mechanism of soybean
      under flooding stress, changes in protein species were analyzed using a
      proteomics approach. Two-day-old soybeans were subjected to flooding for 5 days.
      Proteins were extracted from root, hypocotyl and leaf, and separated by two
      dimensional polyacrylamide gel electrophoresis. In root, hypocotyl and leaf, 51,
      66 and 51 protein species were significantly changed, respectively, under
      flooding stress. In root, metabolism related proteins were increased; however
      these proteins were decreased in hypocotyl and leaf. In all 3 organs, cytoplasm
      localized proteins were decreased, and leaf chloroplastic proteins were also
      decreased. Isoflavone reductase was commonly decreased at protein level in all 3
      organs; however, mRNA of isoflavone reductase gene was up-regulated in leaf under
      flooding stress. Biophoton emission was increased in all 3 organs under flooding
      stress. The up-regulation of isoflavone reductase gene at transcript level; while
      decreased abundance at protein level indicated that flooding stress affected the
      mRNA translation to proteins. These results suggest that concurrence in
      expression of isoflavone reductase gene at mRNA and protein level along with
      imbalance in other disease/defense and metabolism related proteins might lead to
      impaired growth of root, hypocotyl and leaf of soybean seedlings under flooding
      stress.

PMID- 22850270
TI  - Comparative proteome analysis of acute myeloid leukemia with and without
      maturation.
AB  - Acute myeloid leukemia (AML) is a severe, rapidly progressing disease triggered
      by blocking granulocyte or monocyte differentiation and maturation. Because of
      its heterogeneity, AML is divided into a number of subtypes. Unfortunately, so
      far very few correlations have been found between AML classification and its
      clinical course or patient response to treatment. In addition, as yet only a few
      subtype-specific AML biomarkers have been discovered. To solve these problems
      here, we focused on two AML subtypes M1 and M2 that are especially difficult to
      differentiate. Using 2D electrophoresis and mass spectrometry, we analyzed the
      protein profiles of peripheral blood (PB) and/or bone marrow (BM) samples
      collected from 38 AML-M1/M2 patients and 17 healthy volunteers. Comparative
      analysis of AML-M1/M2 and control PB/BM cells revealed 25 proteins that
      accumulated differentially. Hierarchical clustering of proteomic results clearly
      divided the AML samples into 2 groups (M1 and M2). Annexin III, L-plastin and 6
      phosphogluconate dehydrogenase were found only in the M2 group. We also observed
      that the levels of annexin I and actin gamma 1 were correlated with resistance to
      treatment and the time of relapse. It appears that these five proteins can serve
      as potential AML biomarkers.

PMID- 22850271
TI  - Low microsatellite frequencies in neuron and brain expressed microRNAs.
AB  - The locations of microsatellites in mammalian genomes are restricted by purifying
      selection in a number of ways. For example, with the exception of some
      trinucleotide repeats they are excluded from protein coding regions of genomes
      because of their tendency to cause frameshift mutations. Here we investigate
      whether purifying selection might affect the types and frequencies of
      microsatellites in microRNA (miRNA). We concentrate on miRNAs expressed in
      neurons and the brain (NB-miRNAs) as microsatellites in these genes might give
      rise to similar effects as disease-causing repeats in protein coding genes. We
      show that in human miRNAs in general AG and AT microsatellites are reduced in
      frequency compared to AC repeats and that NB-miRNA genes contain significantly
      fewer microsatellites than expected from frequencies of microsatellites in other
      miRNA genes. NB-miRNAs show lower levels of sequence divergence in comparisons of
      human-macaque orthologues and more often have detectable orthologues in non-human
      mammals than non-NB-miRNAs. This suggests that microsatellites in miRNAs may
      indeed be constrained by purifying selection and that the strength of this
      selection may differ between NB-miRNAs and non-NB-miRNAs. We identify a number of
      ways in which the potential disruption of pre-miRNA secondary structure might
      result in purifying selection. However other, non-selective forces could also
      play a role in generating the biases observed in miRNA microsatellites.

PMID- 22850272
TI  - Metagenomic analysis of virulence-associated and antibiotic resistance genes of
      microbes in rumen of Indian buffalo (Bubalus bubalis).
AB  - A major research goal in rumen microbial ecology is to understand the
      relationship between community composition and its function, particularly
      involved in fermentation process is of a potential interest. The buffalo rumen
      microbiota impacts human food safety as well as animal health. Although the
      bacteria of bovine rumen have been well characterized, techniques have been
      lacking to correlate total community structure with gene function. We applied 454
      next generations sequencing technology to characterize general microbial
      diversity present in buffalo rumen metagenome and also identified the repertoire
      of microbial genes present, including genes associated with antibiotic resistance
      and bacterial virulence. Results suggest that over six percent (6.44%) of the
      sequences from our buffalo rumen pool sample could be categorized as virulence
      genes and genes associated with resistance to antibiotic and toxic compounds
      (RATC), which is a higher proportion of virulence genes reported from metagenome
      samples of chicken cecum (5.39%), cow rumen (4.43%) and Sargasso sea (2.95%).
      However, it was lower than the proportion found in cow milk (11.33%) cattle
      faeces (8.4%), Antarctic marine derived lake (8.45%), human fecal (7.7%) and farm
      soil (7.79%). The dynamic nature of metagenomic data, together with the large
      number of RATC classes observed in samples from widely different ecologies
      indicates that metagenomic data can be used to track potential targets and
      relative amounts of antibiotic resistance genes in individual animals. In
      addition, these data can be also used to generate antibiotic resistance gene
      profiles to facilitate an understanding of the ecology of the microbial
      communities in each habitat as well as the epidemiology of antibiotic resistant
      gene transport between and among habitats.

PMID- 22850273
TI  - BLyS expression and JNK activation may form a feedback loop to promote survival
      and proliferation of multiple myeloma cells.
AB  - B-Lymphocyte stimulator (BLyS), a member of tumor necrosis factor superfamily, is
      a potent co-activator of B cells in vitro, and in vivo induces B cell
      proliferation and immunoglobulin secretion. Multiple myeloma (MM) is an incurable
      malignancy of terminally differentiated B cells (plasma cells). Previous studies
      have well ascertained that BLyS plays an important contributory role in the
      pathogenesis and propagation of multiple myeloma by virtue of its ability to
      promote B cell survival, expansion, and differentiation. However, the
      intracellular signaling of BLyS in human MM cells remains undefined. This study
      was designed to see whether there was interaction between MAPK signaling pathway
      and BLyS expression. It was found that the active protein p-JNK was expressed in
      KM3, U266 and PBMCs of MM patients, and that the expression of BLyS could be
      changed by JNK pathway activator and inhibitor. In addition, recombinant BLyS
      activated JNK pathway, while BLyS siRNA treatment inhibited the activation of JNK
      pathway. The level of BLyS expression and the activation of JNK pathway were
      positively correlated. These findings suggest that JNK activation and BLyS
      expression in MM cells may form a positive feedback loop that promotes the
      survival and proliferation of MM cells, and these may shed some light on the
      pathogenesis and treatment of MM.

PMID- 22850274
TI  - Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis
      patients with nodules.
AB  - BACKGROUND: Immunohistochemical studies of the rheumatoid nodule (RN) suggest it
      is a Th1 granuloma, with focal vasculitis, yet the pathogenesis remains unclear
      and little is known about circulating cytokines in these patients. OBJECTIVE: We
      studied circulating cytokines in DMARD-naive RA patients to investigate
      associations with subcutaneous RN. METHODS: 149 DMARD-naive adults with early RA
      (symptom duration <= 2 years) were assessed using the Simplified Disease Activity
      Index (SDAI), and hand and feet radiographs were scored using the modified Larsen
      method. Circulating cytokines and growth factors representative of T-helper cell
      1(Th1) and Th2 cell, macrophages, and fibroblasts were measured using the Bio
      Plex(r) suspension array system. RESULTS: Of 149 patients, 34 (22.8%) had
      subcutaneous RN, and these patients had more severe disease with higher mean
      swollen joint counts (p=0.02), SDAI (p=0.04) and modified Larsen scores
      (p=0.004). There were no differences in Rheumatoid Factor or anti-cyclic
      citrullinated peptide antibody positivity between patients with RN and those
      without RN. Patients with RN showed significantly higher levels of circulating IL
      12 (p=0.02), IL-2 (p=0.048), and VEGF (p=0.033) levels, with a trend towards
      higher levels of IL-7 (p=0.056), IFN-gamma (p=0.059) and IL-8 (p=0.074) compared
      to those without RN. CONCLUSIONS: DMARD-naive early RA patients with RN had more
      severe disease than those without RN, and showed an exaggerated circulating Th1
      and macrophage cytokine profile.

PMID- 22850276
TI  - The effect of aging on the bioavailability of toluene sorbed to municipal solid
      waste components.
AB  - Past practice of co-disposing priority pollutants with municipal solid waste
      (MSW) has led to the placement of more than 150 MSW landfills in the US on the
      National Priorities List of Superfund. Interactions between organic contaminants
      and MSW constituents and the effects of these interactions on contaminant fate
      are poorly understood. The objective of this study was to evaluate the effects of
      sorbate-sorbent aging time and sorbent decomposition on toluene bioavailability
      and fate. The bioavailability of (14)C-toluene sorbed to individual MSW
      constituents [office paper, newsprint, model food and yard waste, high density
      polyethylene (HDPE), and poly(vinyl chloride) (PVC)] was evaluated after aging
      times of 1, 30, and 180 d. Biodegradable sorbents were tested in both fresh and
      anaerobically degraded forms to evaluate the effect of sorbent decomposition. At
      the termination of bioavailability tests, the distribution of (14)C that was not
      converted to (14)CO(2) was measured by sequential lipophilic solvent and base
      extractions of sorbents followed by combustion of extracted sorbents. Increasing
      the toluene-sorbent aging time reduced the rate of toluene biodegradation for all
      MSW components except for HDPE. (14)C remaining in sorbents at the completion of
      bioavailability tests was physically sequestered within and/or covalently bound
      to sorbent organic matter, and this fraction increased with increasing aging
      time. Up to 18.6% of (14)C was associated with humic matter (humic and fulvic
      acids, humin) at the completion of bioavailability tests.

PMID- 22850275
TI  - Brefeldin A, but not monensin, enables flow cytometric detection of interleukin-4
      within peripheral T cells responding to ex vivo stimulation with Chlamydia
      trachomatis.
AB  - Intracellular cytokine staining (ICS) assay optimization should include selection
      of suitable cytokine secretion inhibitors. Here, peripheral blood mononuclear
      cells (PBMC) from women with proven history of C. trachomatis genital tract
      infection were used to compare the ability of brefeldin A (BFA) and monensin (MN)
      to concurrently trap interferon-gamma (IFN-gamma), tumor necrosis factor (TNF),
      interleukin (IL)-4, and IL-17 within T cells responding to ex vivo stimulation
      with chlamydial antigen. While flow cytometric analyses showed similar
      intracellular levels of TNF, IFN-gamma, and IL-17 among T cells treated with BFA
      or both BFA and MN, markedly more IL-4 was found inside T cells treated with BFA
      compared to those that received MN or BFA and MN. The latter findings oppose
      current ICS recommendations informing that ICS results are unaffected by
      concomitant use of BFA and MN, and also suggests that MN may be an unsuitable
      cytokine secretion inhibitor for ICS assays designed to measure intracellular IL
      4 accumulation.

PMID- 22850277
TI  - Bioremediation of strontium (Sr) contaminated aquifer quartz sand based on
      carbonate precipitation induced by Sr resistant Halomonas sp.
AB  - Contamination of aquifers or sediments by radioactive strontium ((90)Sr) is a
      significant environmental problem. In the present study, microbially induced
      calcite precipitation (MICP) was evaluated for its potential to remediate
      strontium from aquifer quartz sand. A Sr resistant urease producing Halomonas sp.
      was characterized for its potential role in bioremediation. The bacterial strain
      removed 80% of Sr from soluble-exchangeable fraction of aquifer quartz sand. X
      ray diffraction detected calcite, vaterite and aragonite along with calcite
      strontianite (SrCO(3)) solid solution in bioremediated sample with indications
      that Sr was incorporated into the calcite. Scanning electron micrography coupled
      with energy-dispersive X-ray further confirmed MICP process in remediation. The
      study showed that MICP sequesters soluble strontium as biominerals and could play
      an important role in strontium bioremediation from both ecological and greener
      point of view.

PMID- 22850278
TI  - Investigating the significance of dissolved organic contaminants in aquatic
      environments: coupling passive sampling with in vitro bioassays.
AB  - We investigated the feasibility of coupling passive sampling and in vitro
      bioassay techniques for both chemical and ecotoxicological assessment of complex
      mixtures of organic contaminants in water. Silicone rubber passive sampling
      devices (SR-PSDs) were deployed for 8-9 weeks in four streams and an estuary of
      an agricultural catchment in North East (NE) Scotland. Extracts from the SR-PSDs
      were analysed for freely dissolved hydrophobic organic contaminants (HOCs) and
      screened for wide range of pesticides. The total concentrations of dissolved PAHs
      (?PAH(40), parent and branched) in the water column of the catchment varied from
      38 to 69 ng L(-1), whilst PCBs (?PCB(32)) ranged 0.02-0.06 ng L(-1). A number and
      level of pesticides and acid/urea herbicides of varying hydrophobicity (logK(OW)s
      ~2.25 to ~5.31) were also detected in the SR extracts, indicating their
      occurrence in the catchment. The acute toxicity and EROD induction potentials of
      SR extracts from the study sites were evaluated with rainbow trout liver
      (Oncorhynchus mykiss; RTL-W1) cell line. Acute cytotoxicity was not observed in
      cells following 48 h exposure to the SR extracts using neutral red uptake assay
      as endpoint. But, on a sublethal level, for every site, statistically significant
      EROD activity was observed to some degree following 72 h exposure to extracts,
      indicating the presence of compounds with dioxin-like effect that are
      bioavailable to aquatic organisms in the water bodies of the catchment.
      Importantly, only a small fraction of the EROD induction could be attributed to
      the PAHs and PCBs that were determined. This preliminary study demonstrates that
      the coupling of silicone rubber passive sampling techniques with in vitro
      bioassays is feasible and offers a cost effective early warning signal on water
      quality deterioration.

PMID- 22850279
TI  - Influence of the exposure way and the time of sacrifice on the effects induced by
      a single dose of pure Cylindrospermopsin on the activity and transcription of
      glutathione peroxidase and glutathione-S-transferase enzymes in Tilapia
      (Oreochromis niloticus).
AB  - Cylindrospermopsin is a cyanobacterial toxin frequently implicated in
      cyanobacterial blooms that is approaching an almost cosmopolitan distribution
      pattern. Moreover, the predominant extracellular availability of this cyanotoxin
      makes it particularly likely to be taken up by a variety of aquatic organisms
      including fish. Recently, Cylindrospermopsin has shown to alter the activity and
      gene expression of some of the glutathione related enzymes in tilapias
      (Oreochromis niloticus), but little is known about the influence of the route of
      exposure and the time of sacrifice after a single exposure to Cylindrospermopsin
      on these biomarkers. With this aim, tilapias were exposed by gavage or by
      intraperitoneal injection to a single dose of 200 MUg kg(-1) bw of pure
      Cylindrospermopsin and after 24h or 5d they were sacrificed. The activity and
      relative mRNA expression by real-time PCR of antioxidant enzymes glutathione
      peroxidase and soluble glutathione-S-transferases (sGST) and the sGST protein
      abundance by Western blot analysis were evaluated in liver and kidney. Results
      showed differential responses in dependence on the variables considered with a
      higher toxicity with the intraperitoneal exposure and with 5d as time of
      sacrifice.

PMID- 22850280
TI  - Dietary galacto-oligosaccharides and calcium: effects on energy intake, fat-pad
      weight and satiety-related, gastrointestinal hormones in rats.
AB  - Galacto-oligosaccharides (GOS) are carbohydrates that are fermented by colonic
      microbiota. The present study examined effects of a 3-week dietary enrichment
      with 6 % (w/w) GOS on parameters of energy balance in forty-three male Wistar
      rats. GOS was tested with two doses of calcium phosphate (30 and 100 mmol/kg),
      known to differently affect colonic fermentation. After 17 d, isoenergetic test
      meals were presented and plasma responses of ghrelin, glucagon-like peptide-1
      (GLP-1) and peptide YY (PYY) were measured. On day 21 (study termination)
      epididymal fat pads and caecum were weighed. Additionally, gastrointestinal
      mucosal samples and proximal colonic contents were analysed for gene expression
      (ghrelin, proglucagon and PYY) and fermentation metabolites (SCFA and lactate),
      respectively. GOS reduced energy intake most prominently during the first week,
      without provoking compensatory overeating later on (average intake reduction: 14
      %). The GOS-fed rats showed increased caecal and reduced fat-pad weight and
      increased gene expression of the satiety-related peptides, PYY (1.7-fold) and
      proglucagon (3.5-fold). Pre-meal baseline and post-meal plasma levels of PYY, but
      not of ghrelin or GLP-1, were higher in GOS-fed rats than in control rats. Ca
      enrichment resulted in higher energy intake (average 4.5 %). GOS diets increased
      lactic acid levels and slightly reduced butyric acid in proximal colonic
      contents. Ca abolished the GOS-related elevation of lactic acid, while increasing
      propionic acid levels, but did not inhibit GOS-related effects on energy intake,
      fat-pad weight or gene expression. These results indicate that dietary GOS
      stimulate a number of physiological mechanisms that can reduce energy intake,
      regardless of the calcium phosphate content of the diet.

PMID- 22850281
TI  - Clinical outcome after vertebral artery injury following blunt cervical spine
      trauma.
AB  - OBJECTIVE: Imaging after blunt cervical trauma is being used increasingly to
      screen patients for injury of the vertebral artery (VA). There are no guidelines
      for imaging of the VA for nonpenetrating cervical trauma. The purpose of this
      study was to determine the effect of VA injury on clinical outcome after blunt
      cervical trauma. METHODS: Sixty-six patients who underwent computed tomographic
      angiography (CTA) and magnetic resonance angiography (MRA) after blunt cervical
      trauma were reviewed. Medical records were reviewed for clinical status,
      including the presence of a neurologic deficit or pain related to spine or
      vascular injury. Any suggested brain injury was evaluated with diffusion-weighted
      MR imaging. Both clinical and radiographic data were analyzed to determine the
      incidence of VA abnormalities and their association with clinical outcome.
      RESULTS: VA abnormalities were present in 19.7% of cases. Two patients had
      symptomatic brain sequelae from VA injury. There was no significant association
      between VA abnormalities and the presence of symptoms and/or cervical spine
      fractures at presentation. The presence of a fracture and neurologic symptoms at
      presentation predicted a significantly worse outcome at a mean follow-up of 5
      months. However, the presence of VA abnormalities did not predict a worse
      clinical outcome. CONCLUSIONS: The clinical outcome of patients with blunt
      cervical trauma was not associated with the presence of VA abnormalities. Given
      the rare but potentially devastating consequences of a VA injury, however,
      screening may still be worthwhile.

PMID- 22850282
TI  - Trans-striatocapsular contralateral interhemispheric resection of anterior
      inferior basal ganglia cavernous malformation.
AB  - OBJECTIVE: To describe a technique to approach the anterior inferior basal
      ganglia. CASE DESCRIPTION: A 29-year-old man presented with several episodes of
      facial droop and a cavernous malformation anterior, inferior, and lateral to the
      head of the caudate nucleus. Several possible surgical approaches were
      considered, including a transsylvian approach and a contralateral
      interhemispheric approach. Ultimately, the patient underwent a contralateral
      interhemispheric trans-striatocapsular approach to the lesion and was discharged
      without neurologic deficit within 72 hours. CONCLUSION: The approach described
      here is a novel alternative to transsylvian or supracarotid approaches to the
      anterior inferior basal ganglia and in this patient provided a well-tolerated
      surgical corridor that allowed complete resection of his cavernoma. We discuss
      several advantages and disadvantages of the various approaches to the anterior
      inferior basal ganglia.

PMID- 22850283
TI  - Endoscopic resection of colloid cysts: use of a dual-instrument technique and an
      anterolateral approach.
AB  - OBJECTIVE: Endoscopic approaches are increasingly utilized to treat third
      ventricular colloid cysts but have been associated with lower rates of complete
      cyst wall resection. Our objective was to assess the results of colloid cyst
      resection via an anterolateral endoscopic approach with a dual-instrument
      technique, with an emphasis on completeness of cyst wall resection. METHODS: A
      retrospective review of the senior author's experience with 22 colloid cysts
      treated with endoscopic resection since 2004 was performed. Initial cyst size,
      completeness of resection, postoperative radiographic residual, recurrence at
      follow-up, need for reoperation, and neurologic morbidity were assessed. All
      cysts were approached from an anterolateral trajectory with two instruments
      working in concert through a single endoscope. RESULTS: Of 22 patients, near
      total resection was obtained in 95%. In 3 cases, a very small, radiographically
      occult residual was left. Complete cyst wall resection was therefore obtained in
      18 (82%). There were no cases of recurrence at follow-up in any patient. No
      patients required craniotomy or underwent re-resection. Fifteen of 16 (94%)
      patients with long-term clinical follow-up remained stable or improved.
      CONCLUSION: High rates of complete colloid cyst resection, with low morbidity,
      are possible with an anterolateral endoscopic approach with dual-instrument
      technique. These results support the findings of other endoscopists that show how
      technical modifications to traditional endoscopic approaches can produce
      favorable results.

PMID- 22850284
TI  - Stem cell factor is responsible for the rapid response in mature mast cell
      density in the acutely stressed heart.
AB  - In the abdominal aortocaval (AV) fistula model of heart failure, we have shown
      that the acute doubling of cardiac mature mast cell (MC) density involved the
      maturation, but not proliferation, of a resident population of immature cardiac
      MCs. An increase in stem cell factor (SCF) may be responsible for this MC
      maturation process. Thus, the purpose of this study was to determine if: 1)
      myocardial SCF levels are increased following the initiation of cardiac volume
      overload; 2) the incubation of left ventricular (LV) tissue slices with SCF
      results in an increase in mature MC density; and 3) chemical degranulation of
      mature cardiac MCs in LV tissue slices results in an increase in SCF and mature
      MC density via MC chymase. Male rats with either sham or AV fistula surgery were
      studied at 6h and 1 and 3 days post-surgery. LV slices from normal male rat
      hearts were incubated for 16h with media alone or media containing one of the
      following: 1) recombinant rat SCF (20 ng/ml) to determine the effects of SCF on
      MC maturation; 2) the MC secretagogue compound 48/80 (20 MUg/ml) to determine the
      effects of MC degranulation on SCF levels and mature MC density; 3) media
      containing compound 48/80 and anti-SCF (5 MUg/ml) to block the effects of SCF; 4)
      chymase (100 nM) to determine the effects of chymase on SCF; and 5) compound
      48/80 and chymostatin (chymase inhibitor, 10 MUM) to block the effects of MC
      chymase. In AV fistula animals, myocardial SCF was significantly elevated above
      that in the sham group at 6h and 1 day post fistula by 2 and 1.8 fold,
      respectively, and then returned to normal by 3 days; this increase slightly
      preceded significant increases in MC density. Incubation of LV slices with SCF
      resulted in a doubling of mature MC density and this was concomitant with a
      significant decrease in the number of immature mast cells. Incubation of LV
      slices with compound 48/80 increased media SCF levels and mature MC density and
      with anti-SCF and chymostatin prevented these compound 48/80-induced increases.
      Incubation with chymase increased media SCF levels and mature MC density. These
      findings indicate that activated mature cardiac mast cells are responsible, in a
      paracrine fashion, for the increase in mature MC density post AV fistula by
      rapidly increasing SCF levels via the release of chymase.

PMID- 22850285
TI  - Translation of Myocyte Enhancer Factor-2 is induced by hypertrophic stimuli in
      cardiomyocytes through a Calcineurin-dependent pathway.
AB  - The Myocyte Enhancer Factor-2 (MEF2) family of transcription factors regulates
      gene expression during cardiomyocyte differentiation and adaptation of the
      myocardium to stress. MEF2 activity is enhanced by increasing its transcription
      and by MAPK-dependent phosphorylation, and is reduced by binding to class-II
      Histone Deacetylases and by miR-1-mediated degradation of its transcript. Here we
      show that MEF2 protein abundance is regulated at the translational level,
      determining myocyte size, during hypertrophy. In order to reduce MEF2 protein
      expression, its silencing through RNA interference required serum deprivation
      and, even in this condition, MEF2 protein abundance recovered to basal levels in
      presence of phenylephrine. Hypertrophic agonist stimulation of neonatal
      ventricular cardiomyocytes increased Mef2 expression by enhancing its
      translation, without changing its transcription or blocking degradation of the
      protein. MEF2 abundance was increased by Calcineurin overexpression in vivo and
      was reduced by Calcineurin inhibition in vitro, without affecting Mef2 mRNA
      levels. Calcineurin activity influenced expression of Polypyrimidine Tract
      Protein (PTB), contributing to MEF2 translation. Thus, our results show a
      previously unrecognized but relevant level of MEF2 activity regulation through
      the control of its translation that involves Calcineurin and PTB.

PMID- 22850287
TI  - Circulating factor VII activating protease (FSAP) is associated with clinical
      outcome in acute coronary syndrome.
AB  - BACKGROUND: Factor VII activating protease (FSAP) is a circulating serine
      protease strongly expressed in unstable plaques and may serve as a marker of
      plaque destabilization. The aim of this study was to examine the relation between
      plasma concentrations of FSAP and clinical instability and outcome in coronary
      artery disease (CAD). METHODS AND RESULTS: Circulating FSAP concentration and
      activity, as well as FSAP mRNA expression in monocytes, were measured in 231
      sequential patients who underwent coronary angiography because of stable angina
      pectoris (n=50), unstable angina pectoris (n=43), or acute myocardial infarction
      (n=87). FSAP activity, but not FSAP antigen concentration, was elevated in
      patients with CAD compared with a control group. Elevated FSAP activity (>=1.035
      plasma equivalent units [PEU]/ml) indicated a significantly increased risk of
      death or non-fatal myocardial infarction during 1 year of follow-up as compared
      with patients with low activity of FSAP (odds ratio 1.895 [95% confidence
      interval 1.093-3.283]; P=0.023). Furthermore, there were no significant changes
      in the FSAP expression in monocytes from CAD and control subjects in the basal
      state but there were differences after stimulation with proinflammatory factors.
      CONCLUSIONS: Plasma FSAP activity was significantly increased in patients with
      acute coronary syndrome and may be involved in the pathogenesis of these
      conditions. High levels of FSAP activity were predictive of adverse events during
      follow-up, suggesting its potential role in risk stratification and clinical
      management of CAD patients.

PMID- 22850286
TI  - Myosin binding protein-C phosphorylation is the principal mediator of protein
      kinase A effects on thick filament structure in myocardium.
AB  - Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) is a regulator of
      pump function in healthy hearts. However, the mechanisms of regulation by cAMP
      dependent protein kinase (PKA)-mediated cMyBP-C phosphorylation have not been
      completely dissociated from other myofilament substrates for PKA, especially
      cardiac troponin I (cTnI). We have used synchrotron X-ray diffraction in skinned
      trabeculae to elucidate the roles of cMyBP-C and cTnI phosphorylation in
      myocardial inotropy and lusitropy. Myocardium in this study was isolated from
      four transgenic mouse lines in which the phosphorylation state of either cMyBP-C
      or cTnI was constitutively altered by site-specific mutagenesis. Analysis of peak
      intensities in X-ray diffraction patterns from trabeculae showed that cross
      bridges are displaced similarly from the thick filament and toward actin (1) when
      both cMyBP-C and cTnI are phosphorylated, (2) when only cMyBP-C is
      phosphorylated, and (3) when cMyBP-C phosphorylation is mimicked by replacement
      with negative charge in its PKA sites. These findings suggest that
      phosphorylation of cMyBP-C relieves a constraint on cross-bridges, thereby
      increasing the proximity of myosin to binding sites on actin. Measurements of
      Ca(2+)-activated force in myocardium defined distinct molecular effects due to
      phosphorylation of cMyBP-C or co-phosphorylation with cTnI. Echocardiography
      revealed that mimicking the charge of cMyBP-C phosphorylation protects hearts
      from hypertrophy and systolic dysfunction that develops with constitutive
      dephosphorylation or genetic ablation, underscoring the importance of cMyBP-C
      phosphorylation for proper pump function.

PMID- 22850288
TI  - Noninvasive ventilation in pulmonary edema complicating acute myocardial
      infarction.
AB  - BACKGROUND: Because it remains unclear whether noninvasive ventilation (NIV) is
      an effective therapy for cardiogenic pulmonary edema secondary to acute
      myocardial infarction (AMI), we retrospectively evaluated our experience with NIV
      in the treatment of pulmonary edema secondary to AMI and other cardiac
      conditions. METHODS AND RESULTS: The study group included 206 patients with
      cardiogenic pulmonary edema, divided into an AMI group (53 patients) and a non
      AMI group (153 patients). The weaning rate from NIV was similar in the AMI and
      non-AMI groups (90.6% vs. 90.8%, P=0.950). Heart rate, blood pressure, and
      respiratory rate decreased significantly 1h after initiation of NIV in both
      groups, and were maintained until weaning from NIV. The frequency of endotracheal
      intubation after weaning from NIV was higher in the AMI group than in the non-AMI
      group (7.5% vs. 0.7%, P=0.016), although the overall frequency of intubation was
      similar in both groups. The in-hospital mortality rate was similar in the AMI and
      non-AMI groups (13.1% vs. 9.8%, P=0.489). CONCLUSIONS: NIV effectively improved
      vital signs and oxygenation and lowered the intubation rate in patients with
      cardiogenic pulmonary edema of all etiologies, including AMI. The outcome in
      patients with AMI treated with NIV depends primarily on the severity of the
      course of AMI and not on the severity of acute respiratory failure.

PMID- 22850289
TI  - J-ROCKET AF trial increased expectation of lower-dose rivaroxaban made for Japan.

PMID- 22850290
TI  - Enhanced preclinical efficacy of tamoxifen developed as alginate
      cysteine/disulfide bond reduced albumin nanoparticles.
AB  - Tamoxifen (TMX) is the most common clinical choice for the treatment of advanced
      or metastatic estrogen-dependent breast cancer. However, research on new
      challenging therapies is necessary due to its undesirable side effects and the
      limitation of the treatment only to the oral route. In this study, the antitumor
      activity of TMX-loaded nanoparticles based on different mixtures of alginate
      cysteine and disulfide bond reduced bovine serum albumin was tested in vivo in
      MCF-7 nude mice xenograft model. These systems showed an enhancement of the TMX
      antitumor activity, since lower tumor evolutions and lower tumor growth rates
      were observed in mice treated with them. Moreover, histological and
      immunohistochemical studies revealed that treatments with TMX-loaded
      nanoparticles showed the most regressive and less proliferative tumor tissues.
      TMX biodistribution studies determined that TMX-loaded nanoparticles caused more
      accumulation of the drug into the tumor site with undetectable levels of TMX in
      plasma, reducing the possibility of delivering TMX to other not-targeted organs
      and, consequently, developing possible side effects. Thus, these TMX
      nanoparticulate systems are expected to provide a novel approach to the treatment
      of breast cancer in the future.

PMID- 22850292
TI  - Evaluating the effects of buffer conditions and extremolytes on thermostability
      of granulocyte colony-stimulating factor using high-throughput screening combined
      with design of experiments.
AB  - In this study, we combined a high-throughput screening method, differential
      scanning fluorimetry (DSF), with design of experiments (DoE) methodology to
      evaluate the effects of several formulation components on the thermostability of
      granulocyte colony stimulating factor (G-CSF). First we performed a primary
      buffer screening where we tested thermal stability of G-CSF in different buffers,
      pH values and buffer concentrations. The significance of each factor and the two
      way interactions between them were studied by multivariable regression analysis.
      pH was identified as most critical factor regarding thermal stability. The most
      stabilizing buffer, sodium glutamate, and sodium acetate were determined for
      further investigations. Second we tested the effect of 6 naturally occurring
      extremolytes (trehalose, sucrose, ectoine, hydroxyectoine, sorbitol, mannitol) on
      the thermal stability of G-CSF, using a central composite circumscribed design.
      At low pH (3.8) and low buffer concentration (5 mM) all extremolytes led to a
      significant increase in thermal stability except the addition of ectoine which
      resulted in a strong destabilization of G-CSF. Increasing pH and buffer
      concentration led to an increase in thermal stability with all investigated
      extremolytes. The described systematic approach allowed to create a ranking of
      stabilizing extremolytes at different buffer conditions.

PMID- 22850291
TI  - Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier
      improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin
      derivative.
AB  - Elastin-like polypeptide (ELP) is a macromolecular carrier with thermally
      responsive properties that can passively accumulate in solid tumors and
      additionally aggregate in tumor tissue when exposed to hyperthermia. In this
      study, ELP was conjugated to the anticancer drug doxorubicin (DOXO) and three
      different cell penetrating peptides (CPP) in order to inhibit tumor growth in
      mice compared to free doxorubicin. Fluorescence microscopy studies in MCF-7
      breast carcinoma cells demonstrated that the three different CPP-ELP-DOXO
      conjugates delivered doxorubicin to the cell nucleus. All CPP-ELP-DOXO conjugates
      showed cytotoxicity with IC(50) values in the range of 12-30 MUM at 42  degrees
      C, but the ELP carrier with SynB1 as the cell penetrating peptide had the lowest
      intrinsic cytotoxicity. Therefore, the antitumor efficacy of SynB1-ELP-DOXO was
      compared to doxorubicin under hyperthermic conditions. C57BL/6 female mice
      bearing syngeneic E0771 murine breast tumors were treated with either free
      doxorubicin or the SynB1-ELP-DOXO conjugate with or without focused hyperthermia
      on the tumor. Under hyperthermic conditions, tumor inhibition with SynB1-ELP-DOXO
      was 2-fold higher than under therapy with free doxorubicin at the equivalent
      dose, and is thus a promising lead candidate for optimizing thermally responsive
      drug polymer conjugates.

PMID- 22850293
TI  - Accelerated blood clearance of PEGylated liposomes containing doxorubicin upon
      repeated administration to dogs.
AB  - The accelerated blood clearance phenomenon involving anti-PEG IgM production has
      been recognized as an important issue for the design and development of PEGylated
      liposomes. Here, we show that empty PEGylated liposomes and Doxil, PEGylated
      liposomes containing doxorubicin, both caused anti-PEG IgM production and thereby
      a rapid clearance of the second and/or third dose of Doxil in Beagle dogs in a
      lipid-dose, inverse-dependent manner. It appears that the pharmacokinetic profile
      of the second and third administration of Doxil reflected the presence of anti
      PEG IgM circulating in the blood. Doxil plus an excess amount of empty PEGylated
      liposomes rather enhanced the production of anti-PEG IgM compared to Doxil of the
      same doxorubicin dose. During sequential administration, increasing the lipid
      dose of Doxil in each dose by the addition of empty PEGylated liposomes strongly
      attenuated the magnitude of the ABC phenomenon during the effectuation phase of a
      second and third dose of Doxil. Our results suggest that the pre-clinical study
      of anti-cancer drug-containing PEGylated liposomes with dogs must be carefully
      designed and performed with monitoring of the anti-PEG IgM and liposomal drugs
      circulating in the blood.

PMID- 22850294
TI  - A novel hybrid delivery system: polymer-oil nanostructured carrier for controlled
      delivery of highly lipophilic drug all-trans-retinoic acid (ATRA).
AB  - Many recently developed drugs encounter delivery issues due to their high
      lipophilicity and poor aqueous solubility. This study reports the development of
      a novel hybrid nanocarrier known as polymer-oil nanostructured carrier (PONC), in
      which highly lipophilic drugs such as all-trans-retinoic acid (ATRA) and
      indomethacin pre-solubilized in oil phase were dispersed in a polymeric matrix of
      poly(D,L-lactic-co-glycolic acid) (PLGA). In comparison to the standard PLGA only
      nanoparticles, PONC substantially increased the encapsulation efficiency of ATRA
      and indomethacin by up to 259% and 124%, respectively. Differential scanning
      calorimetry analysis revealed that the inclusion of oil introduced nanostructure
      into the polymeric matrix of the carrier. This feature facilitated more uniform
      distribution of the drug molecules which subsequently led to improved drug
      release kinetics with significantly reduced burst release effects (p<0.05). PONC
      was lyophilizable, remained physically stable when stored at low temperatures,
      and demonstrated low non-specific carrier toxicity. Delivery of ATRA by PONC also
      significantly improved its anticancer activity over the standard PLGA only
      nanoparticles (p<0.05). Our findings have therefore validated a promising
      delivery system that integrates the advantages of lipid-based (e.g. efficient
      encapsulation of highly lipophilic drugs) and polymeric colloidal carriers (e.g.
      uniform size, good stability), plus potential therapeutic benefits for delivery
      of poorly water-soluble anticancer drugs like ATRA.

PMID- 22850295
TI  - Evaluation of the effect of plant sterols on the intestinal processing of
      cholesterol using an in vitro lipolysis model.
AB  - An in vitro lipolysis model was utilized to study the effect of stigmastanol
      (lipophilic phytosterol) and disodium ascorbyl phytostanol phosphate (DAPP)
      (modified hydrophilic phytostanol) on intestinal processing of cholesterol to
      gain further understanding of their cholesterol lowering mechanism. Lipolysis
      results showed that stigmastanol, if given in powder alone, had no effect on
      cholesterol processing probably due to its poor solubility. Stigmastanol
      suspension formulation re-distributed cholesterol from aqueous phase to oil and
      sediment phases. The water soluble DAPP has changed cholesterol distribution even
      more significantly by transferring cholesterol from aqueous phase to sediment
      phase. Moreover, the results provided evidence that DAPP inhibited triglyceride
      digestion in vitro. Considering DAPP as a surfactant with the same lipophilic
      sterol ring as bile salt, its ability to inhibit triglyceride lipolysis may be
      due to its competition with bile salt for the substrate surface, thereby
      hindering the lipolysis of triglyceride and inhibiting cholesterol solubilization
      with the lipolysis products. It can be speculated that the cholesterol lowering
      mechanism of DAPP during intestinal digestion is related to its ability to act as
      a surfactant closely resembling bile salt.

PMID- 22850296
TI  - Sirolimus solid self-microemulsifying pellets: formulation development,
      characterization and bioavailability evaluation.
AB  - To enhance the dissolution and oral absorption of water insoluble drug sirolimus
      (SRL), self-microemulsifying pellets of SRL were developed and evaluated.
      Solubility test, self-emulsifying grading test, ternary phase diagrams and
      central composite design were adopted to screen and optimize the composition of
      liquid SRL-SMEDDS. The selected liquid SRL-SMEDDS formulations were prepared into
      pellets by extrusion-spheronization method and the optimal formulation of 1mg SRL
      SMEDDS pellets capsule (1.0, 22.4, 38.4, 19.2, 121.6, 30.4 and 8.0 mg of SRL,
      Labrafil M1944CS, Cremophor EL, Transcutol P, MCC, Lactose and CMS-Na,
      respectively) was finally determinated by the feasibility of the preparing
      process and redispersibility. The optimal SRL-SMEDDS pellets showed a significant
      quicker redispersion rate than the dissolution rate of commercial SRL tablets
      Rapamune in water. The droplet size and polydispersity index of the reconstituted
      microemulsion was almost unchanged after solidification, and pellet size and
      friability were all qualified. Visual observation and scanning electron
      microscopic analysis confirmed good appearance of the solid pellets. DSC, XRPD,
      and IR analysis confirmed that there was no crystalline sirolimus in the pellets.
      Pharmacokinetic study in beagle dogs showed the oral relative bioavailability of
      SRL-SMEDDS pellets to the commercial SRL tablets Rapamune was about 136.9%. In
      conclusion, the solid SMEDDS pellets might be an encouraging strategy to improve
      the oral absorption of SRL and the extrusion-spheronization method was a feasible
      technology for the solidification of liquid SMEDDS.

PMID- 22850297
TI  - Antithymocyte globulin induction in living donor renal transplant recipients:
      final report of the TAILOR registry.
AB  - BACKGROUND: The Thymoglobulin Antibody Immunosuppression in Living Donor
      Recipients registry was established to assess clinical experience with rabbit
      antithymocyte globulin (rATG; Thymoglobulin) in living donor renal transplant
      recipients. METHODS: From 2003 to 2008, US transplant centers prospectively
      entered information on patients who received rATG induction. In addition to
      standard United Network for Organ Sharing registry data elements, information was
      collected regarding immunosuppression, viral prophylaxis, acute rejection, and
      adverse events. RESULTS: Data on 2322 patients from 49 transplant centers were
      enrolled and met inclusion criteria for analysis. Patient and graft survival were
      99.3% and 99.0% at 6 months and 98.4% and 98.2% at 12 months as recorded in
      Thymoglobulin Antibody Immunosuppression in Living Donor Recipients registry and
      were 91.5% and 83.2% at 5 years by Kaplan-Meier estimates based on linked United
      Network for Organ Sharing registry records. Freedom from rejection was 93.6%
      through 5 years. Mean rATG cumulative dose was 5.29 mg/kg. More than one-third of
      patients (37.6%) were steroid-free at discharge, and nearly half of patients
      (48%) were steroid-free at 12 months. Before discharge, 3.2% experienced serious
      adverse events, with 11 events (0.005%) reported as possibly or probably related
      to rATG. Incidence of cytomegalovirus infection was 4.2% at 12 months, and 99.1%
      of patients were posttransplant lymphoproliferative disorder-free through 5
      years. CONCLUSIONS: rATG induction in living donor renal transplantation is safe
      and associated with a low incidence of acute rejection and posttransplantation
      complications.

PMID- 22850298
TI  - Depression in childhood and adolescence: a prospective study of six cases. 1983.

PMID- 22850299
TI  - Temperament: then and now.
AB  - One of many publications emanating from the New York Longitudinal Study (NYLS),
      the prospective study of Stella Chess, Alexander Thomas, and Mahin Hassibi of six
      cases of depression during childhood and adolescence, which appeared in the
      Journal of Nervous and Mental Disease in 1983, provides an opportunity to reflect
      on the climate in which the NYLS was conceived and conducted. Its methodology is
      reviewed, and principle findings are summarized. In the more than 50 years since
      the inception of the NYLS, the attention of temperament investigators has shifted
      from a focus on definition and measurement to the examination of relations
      between temperament and psychopathology, including the exploration of the
      neurocircuitry underlying different dimensions of temperament and their
      contributions to the etiology, pathogenesis, and treatment of axis I disorders in
      developing children.

PMID- 22850300
TI  - Generalized anxiety disorder: between neglect and an epidemic.
AB  - This article reviews the main issues associated with the concept and the
      diagnosis of generalized anxiety disorder (GAD) and examines the proposed DSM-5
      diagnostic criteria for GAD. The lack of specific features, which is the primary
      issue for GAD, will not be addressed in DSM-5. The hallmark of the condition will
      remain pathological worry, although it also characterizes other disorders.
      Likewise, the proposed behavioral diagnostic criteria lack specificity for GAD,
      and it is not clear how these will be assessed. The proposed changes will lower
      the diagnostic threshold for GAD in DSM-5. Although this will not necessarily
      lead to a better recognition of GAD and an improvement in the perception of its
      relevance and clinical utility, many currently subthreshold cases will qualify
      for this diagnosis. The likely inclusion of many such "false-positives" will
      result in an artificial increase in the prevalence of GAD and will have further
      negative consequences.

PMID- 22850302
TI  - Hopelessness, defeat, and entrapment in posttraumatic stress disorder: their
      association with suicidal behavior and severity of depression.
AB  - Research has shown an increased frequency of suicidal behaviors in those with
      PTSD, but few studies have investigated the factors that underlie the emergence
      of suicidal behavior in PTSD. Two theories of suicide, the Cry of Pain and the
      Schematic Appraisal Model of Suicide, propose that feelings of hopelessness,
      defeat, and entrapment are core components of suicidality. This study aimed to
      examine the association between suicidal behavior and hopelessness, defeat, and
      entrapment in trauma victims with and without a PTSD diagnosis. The results
      demonstrated that hopelessness, defeat, and entrapment were significantly
      positively associated with suicidal behavior in those with PTSD. Hopelessness and
      defeat were also significantly positively associated with suicidal behavior in
      trauma victims without PTSD. In those with PTSD, the relationship between
      suicidal behavior and hopelessness and entrapment remained significant after
      controlling for comorbid depression. The findings provide support for the
      contemporary theories of suicidality and have important clinical implications.

PMID- 22850301
TI  - Textual data in psychiatry: reasoning by analogy to quantitative principles.
AB  - Personal meaning in subjective experience is a key element in the treatment of
      persons with mental disorders. Open-response speech samples would appear to be
      suitable for studying this type of subjective experience, but there are still
      important challenges in using language as data. Scientific principles involved in
      sample size calculation, validity, and reliability may be applicable, by analogy,
      to data collected in the form of words. We describe a rationale for including
      computer-assisted techniques as one step of a qualitative analysis procedure that
      includes manual reading. Clarification of a framework for including language as
      data in psychiatric research may allow us to more effectively bridge biological
      and psychometric research with clinical practice, a setting where the patient's
      clinical "data" are, in large part, conveyed in words.

PMID- 22850303
TI  - Victimization and perpetration of intimate partner violence and substance use
      disorders in a nationally representative sample.
AB  - The aim of this study was to examine the relationship between perpetration and
      victimization of physical and sexual intimate partner violence (IPV) in the past
      year and substance use disorders (SUDs) in the past year, including alcohol,
      sedatives/tranquilizers, cocaine, cannabis, and nicotine stratified according to
      sex. Data were from the National Epidemiologic Survey on Alcohol and Related
      Conditions. A series of adjusted logistic regression models were conducted. Among
      men and women, all types of SUDs were associated with increased odds of IPV
      perpetration (odds ranging from 1.4 to 8.5 adjusting for sociodemographic
      variables). IPV victimization increased the odds of having all types of SUDs for
      male and female victims, with the exception of sedatives/tranquilizer
      abuse/dependence among women (odds ranging from 1.5 to 6.0 adjusting for
      sociodemographic variables). Substances that had the most robust relationship
      with perpetration and victimization of IPV included alcohol and cannabis, after
      adjusting for sociodemographic variables, mood disorders, anxiety disorders,
      personality disorders, and mutual violence.

PMID- 22850304
TI  - The Child Posttraumatic Stress Disorder Checklist in a sample of South African
      youth: establishing factorial validity.
AB  - To address the diverse health effects of posttraumatic stress disorder (PTSD) in
      youth, reliable and valid screening and diagnostic instruments that can be
      adapted to the specific context in which they are used, are required. Here, we
      assessed the psychometric properties (factorial validity, concurrent validity,
      and internal consistency) of the Child PTSD Checklist in treatment-seeking youth
      using secondary data. The scale demonstrated high internal consistency (Cronbach
      alpha = 0.93). Exploratory factor analysis revealed a three-factor structure
      (anxiety and avoidance, anger and dissociation, and depressive symptoms) that
      accounted for 41.9% of the total variance. Concurrent validity was fair between
      the Child PTSD Checklist and the diagnostic Kiddie Schedule for Affective
      Disorders and Schizophrenia, Present and Lifetime version when assessing for
      PTSD. The Child PTSD Checklist seems to be a promising tool for assessing PTSD in
      trauma-exposed youth in clinic settings. However, further studies are needed to
      address the checklist's broader utility.

PMID- 22850305
TI  - Shame, intimacy and self-definition: an assessment of the emotional foundation
      and intimate relationship consequences of an introjective personality
      orientation.
AB  - The current study sought to elaborate and test a theoretical proposition that
      introjective personality functioning, which has been implicated in various
      psychological difficulties (e.g., self-critical depression, obsessive-compulsive
      disorder), has an emotional foundation in the self-conscious emotion of shame and
      is supported by dissociation. Moreover, introjective functioning was predicted to
      be associated with reduced interpersonal intimacy. To test the model, a Web-based
      survey design using path analysis was used. Three hundred and fifteen university
      students were assessed with measures of self-conscious emotions (i.e., shame,
      guilt, and embarrassment), introjective (self-definition) and anaclitic
      (relational) personality style, pathological dissociation, and interpersonal
      intimacy. Introjective personality was found to be associated with increased
      shame and reduced interpersonal intimacy. However, the path between pathological
      dissociation and introjective functioning was not significant. The results are
      discussed with reference to the moderating influence of introjective functioning
      between shame and reduced interpersonal intimacy.

PMID- 22850306
TI  - Predictors of change in functional competence and functional behavior after
      functional adaptation skills training for schizophrenia.
AB  - Functional recovery is an important treatment target in schizophrenia. Although
      medication is effective at reducing positive symptoms of the disorder, these
      improvements do not translate to improved functioning. In this study,
      schizophrenia outpatients (N = 54) received the psychosocial treatment Functional
      Adaptation Skills Training. Hierarchical regression analyses determined whether
      baseline neurocognitive, symptom, course of illness, and demographic variables
      predicted improvement in performance-based measures of functional competence and
      case manager-rated real-world behavior after the intervention. Consistent with
      previous research, neurocognition emerged as a predictor of improved competence
      and behavior. Symptoms played a minor role in predicting change; however,
      institutionalization history seemed to be an important rate limiter for
      functional recovery. Correlations among change scores were modest, with evidence
      for concomitant changes in competence and performance. The predictors of change
      after psychosocial treatment vary by the domain (e.g., adaptive and
      interpersonal) of functioning and the level of assessment (e.g., competence and
      performance).

PMID- 22850307
TI  - The Quick Inventory of Depressive Symptomatology, clinician rated and self
      report: a psychometric assessment in Chinese Americans with major depressive
      disorder.
AB  - This study aimed to investigate the psychometric properties of the Chinese
      translations of the Quick Inventory of Depressive Symptomatology (QIDS(16)),
      including the Clinician-Rated (QIDS-C(16)), Self-report (QIDS-SR(16)), and
      Interactive Voice Response (QIDS-SR-IVR(16)) formats. Thirty depressed Chinese
      Americans were assessed with Chinese translations of the QIDS-SR(16), QIDS-SR
      IVR(16), and QIDS-C(16). Cronbach alpha estimates of internal scale consistency
      on the QIDS-SR(16), QIDS-SR-IVR(16), and QIDS-C(16) were 0.70, 0.74, and 0.79,
      respectively. Intercorrelations among the measures were QIDS-SR(16) and QIDS-SR
      IVR(16), r = 0.79; QIDS-SR(16) and QIDS-C(16), r = 0.61; and QIDS-SR-IVR(16) and
      QIDS-C(16), r = 0.69 (all p values < 0.01). The areas under the curve for the
      receiver operating characteristics of the QIDS-SR(16) and QIDS-SR-IVR(16) were
      0.78 (95% confidence interval, 0.61-0.95) and 0.81 (95% confidence interval, 0.65
      0.96), respectively. The respective screening sensitivities/specificities were
      0.73/0.74 and 0.86/0.58. The Chinese translations of the QIDS(16) have adequate
      psychometric properties and may be useful tools for depression screening.

PMID- 22850308
TI  - Sexual behavior, body image, and partnership in chronic illness: a comparison of
      Huntington's disease and multiple sclerosis.
AB  - Huntington's disease (HD) and multiple sclerosis (MS) are both chronic
      progressive illnesses posing a serious challenge to affected patients and
      families. Sexual dysfunction in HD as well as in MS is a very common problem,
      although it is unclear whether the dysfunction is caused by the chronic illness
      itself or by the sociopsychiatric burden related to the illness. Twenty-nine
      patients with HD and 27 patients with MS each participated in a semistructured
      interview and several standardized questionnaires concerning partnership, sexual
      function, and body image. The results display significant differences in both
      patient groups, displaying higher sexual desire and activity in HD patients, but
      MS patients also reported fewer sexual problems compared to the norming values.
      Conversely, the MS patients' relationships seemed to be stable despite
      subjectively perceived lower initiative on sexual activities. The results are
      discussed under the possible influences of the underlying organic changes and the
      psychosocial consequences of chronic progressive disorders.

PMID- 22850309
TI  - Can activation of coagulation and impairment of fibrinolysis in patients with
      anxiety and depression be reversed after improvement of psychiatric symptoms?
      Results of a pilot study.
AB  - Anxiety and depression are associated with an activation of coagulation and
      impairment of fibrinolysis. This study addresses the question whether these
      findings are reversed after psychotherapy and improvement of psychiatric
      symptoms. Three factors of coagulation and fibrinolysis as well as level of
      anxiety and depression were reassessed in 12 patients 1 to 3 years after
      intensive inpatient psychotherapy. The patients showed a substantial improvement
      of their severe anxiety disorder and comorbid depressive disorder.
      Simultaneously, we found a significant decrease in factor VII and plasminogen
      activator inhibitor. We conclude that reduction of severe anxiety and depression
      may be associated with a reversal of the procoagulant effect (activation of
      coagulation and impairment of fibrinolysis) of these psychological states.
      Because of the small sample size of this pilot study, further research is needed.

PMID- 22850310
TI  - Neurocognition and cognitive biases in schizophrenia.
AB  - Individuals with schizophrenia have been found to exhibit a number of information
      processing biases that may play a role in the development and exacerbation of
      symptoms and may impair overall functioning. However, little is known about the
      factors that are associated with these cognitive biases. Recently, researchers
      have begun to consider whether neurocognitive deficits, common in schizophrenia,
      may be risk factors for the development of cognitive biases. In the present
      study, we assessed neurocognition (verbal learning, delayed verbal recall memory,
      and verbal recognition memory) and cognitive biases (knowledge corruption and
      impaired cognitive insight) in 72 individuals with schizophrenia or
      schizoaffective disorder. As hypothesized, poorer delayed verbal recall memory
      was associated with increased knowledge corruption. Contrary to expectations,
      verbal learning and verbal memory were not associated with cognitive insight.
      These findings suggest that an inadequate recall memory system may put patients
      with schizophrenia at greater risk for cognitive distortions.

PMID- 22850311
TI  - Sex differences in shoplifting: results from a national sample.
AB  - This study presents the sex differences in sociodemographics and in psychiatric
      correlates of shoplifting in the United States. Data were drawn from the National
      Epidemiologic Survey on Alcohol and Related Conditions, a nationally
      representative sample of US adults. Shoplifting was associated with numerous
      psychiatric and addictive disorders with significant sex effects. Women with a
      lifetime history of shoplifting were significantly more likely than men with a
      lifetime history of shoplifting to have a lifetime diagnosis of alcohol abuse or
      dependence, nicotine dependence, cannabis, amphetamine, cocaine, or inhalant use
      disorder, and antisocial personality disorder, whereas men were significantly
      more likely than women to have a lifetime diagnosis of generalized anxiety
      disorder. The findings suggest that shoplifting could be better understood as a
      behavioral manifestation of a broader impaired impulse control spectrum in women.
      Shoplifting could be more a part of the externalizing spectrum disorders rather
      than the internalizing spectrum disorders in women compared to men.

PMID- 22850312
TI  - Are vascular factors linked to the development of hippocampal atrophy in
      Alzheimer's disease?
AB  - The hipppocampus is a brain structure located deep in the temporal lobe and is
      notable for its susceptibility to neurotoxic stimuli. It plays a vital role in
      governing learning and memory. It has been shown to be damaged by variety of
      factors, e.g., hypoxia, hypoperfusion, hypoglycemia, stress, and seizures, and
      the list of such factors keeps growing with time. Recently, the role of vascular
      factors in Alzheimer's disease in causing significant hippocampal damage has
      started emerging. Vascular factors are known to cause cerebral microlesions and
      contribute to many more brain pathologies. Though evidence supporting their
      effects on causing regional brain atrophy is mixed, several studies are
      indicating that medial temporal lobe may be particularly vulnerable to the damage
      caused by cardiovascular risk factors. Considering the association between
      neurodegeneration and vascular factors, a more rigorous scientific evaluation of
      the correlation between these two has been suggested.

PMID- 22850313
TI  - Cognitive function in small vessel disease: the additional value of diffusion
      tensor imaging to conventional magnetic resonance imaging: the RUN DMC study.
AB  - The structural integrity of the cerebral white matter, including that of the
      white matter lesions (WML) and of the surrounding normal appearing white matter
      (NAWM), can be assessed with diffusion tensor imaging (DTI), which is suggested
      to be of added value in the explanation of cognitive dysfunction in cerebral
      small vessel disease (SVD). We investigated the value of DTI of NAWM and WML in
      addition to conventional magnetic resonance imaging (MRI) parameters in the
      variance of cognitive performance in subjects with SVD. 499 individuals with SVD,
      50-85 years, without dementia, underwent MRI scanning, including a DTI sequence.
      Grey matter, white matter (WM), and WML volume, number of microbleeds, lacunar
      and territorial infracts, and mean diffusivity (MD) and fractional anisotropy
      (FA) in NAWM, WML, and total WM were related to cognitive performance in
      multivariate regression analyses, after adjustment for age, gender, and
      education. All MRI parameters together accounted for 1-6% of the variance in
      cognitive function on top of 22-36% already explained by age, gender, and level
      of education. Both mean MD and FA of the NAWM, WML, and total WM did not
      substantially contribute to the explained variance of cognitive function, to that
      already explained by conventional MRI parameters. When considered separately, the
      MD of the (NA)WM had the strongest association with cognitive performance. In
      conclusion, DTI of NAWM and WML has limited additional value to conventional MRI
      parameters in the etiological explanation of the variance in cognitive function
      among individuals with SVD.

PMID- 22850314
TI  - Low-level light therapy improves cortical metabolic capacity and memory
      retention.
AB  - Cerebral hypometabolism characterizes mild cognitive impairment and Alzheimer's
      disease. Low-level light therapy (LLLT) enhances the metabolic capacity of
      neurons in culture through photostimulation of cytochrome oxidase, the
      mitochondrial enzyme that catalyzes oxygen consumption in cellular respiration.
      Growing evidence supports that neuronal metabolic enhancement by LLLT positively
      impacts neuronal function in vitro and in vivo. Based on its effects on energy
      metabolism, it is proposed that LLLT will also affect the cerebral cortex in vivo
      and modulate higher-order cognitive functions such as memory. In vivo effects of
      LLLT on brain and behavior are poorly characterized. We tested the hypothesis
      that in vivo LLLT facilitates cortical oxygenation and metabolic energy capacity
      and thereby improves memory retention. Specifically, we tested this hypothesis in
      rats using fear extinction memory, a form of memory modulated by prefrontal
      cortex activation. Effects of LLLT on brain metabolism were determined through
      measurement of prefrontal cortex oxygen concentration with fluorescent quenching
      oximetry and by quantitative cytochrome oxidase histochemistry. Experiment 1
      verified that LLLT increased the rate of oxygen consumption in the prefrontal
      cortex in vivo. Experiment 2 showed that LLLT-treated rats had an enhanced
      extinction memory as compared to controls. Experiment 3 showed that LLLT reduced
      fear renewal and prevented the reemergence of extinguished conditioned fear
      responses. Experiment 4 showed that LLLT induced hormetic dose-response effects
      on the metabolic capacity of the prefrontal cortex. These data suggest that LLLT
      can enhance cortical metabolic capacity and retention of extinction memories, and
      implicate LLLT as a novel intervention to improve memory.

PMID- 22850315
TI  - The imbalance of vascular molecules in Alzheimer's disease.
AB  - The vascular system plays an integral role during Alzheimer's disease (AD). Both
      systemic circulatory changes and alterations directly within the brain
      vasculature have been suggested to contribute to both the onset and progression
      of neurological conditions such as AD. It is now well established that vascular
      risk factors including hypertension, diabetes, obesity, atherosclerosis,
      metabolic syndrome, and stroke significantly increase one's risk of later
      developing AD. Research within the last decade has begun to identify specific
      vascular molecules associated with such risk factors as well as elucidate the
      biological role they may play in the pathological processes linked to AD. This
      review aims to provide an overview of some of the key molecules within vascular
      cells and circulating in blood that have been identified to be altered in AD
      pathogenesis. In particular, the vascular-specific transcription factors MEOX2,
      MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and
      circulating molecules such as sLRP1, homocysteine, and albumin are discussed. I
      aim to clarify how these identified vascular molecules may help to predict,
      explain, and influence the incidence AD. A strong emphasis is placed on the
      concept that these molecules play overlapping roles in cardiovascular disease
      progression, neurovascular dysfunction, and amyloid-beta pathology. The studies
      reviewed here have identified vascular-based molecular targets in AD and thus
      provide new therapeutic avenues for the treatment of this devastating disease.

PMID- 22850316
TI  - Neuroangiogenesis: a vascular basis for Alzheimer's disease and cognitive decline
      during aging.
AB  - Angiogenesis directs development of the brain's microcirculation during antenatal
      and postnatal development, but its role later in life is less well recognized. I
      contend that during senescence a reduced cerebral capillary density accounts in
      part for the vascular cognitive impairment observed in many older persons and
      possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis
      is essential throughout adult life for maintaining the microcirculation of the
      cerebral cortex and elsewhere in the brain and that it commonly declines with old
      age. To support this hypothesis I have examined the neurological literature for
      relevant studies on cerebral capillary density and neuroangiogenesis throughout
      the three stages of life and in persons with senile dementias. Finally, I discuss
      therapeutic approaches employing angiogenic factors for treating vascular
      cognitive impairment and Alzheimer's disease.

PMID- 22850317
TI  - Negative effect of a low-carbohydrate, high-protein, high-fat diet on small
      peripheral artery reactivity in patients with increased cardiovascular risk.
AB  - Low-carbohydrate diets have become increasingly popular for weight loss. Although
      they may improve some metabolic markers, particularly in type 2 diabetes mellitus
      (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function
      remains unclear. The objective was to evaluate the relation between dietary
      macronutrient composition and the small artery reactive hyperaemia index (saRHI),
      a marker of small artery endothelial function, in a cohort of patients at
      increased cardiovascular (CV) risk. The present cross-sectional study included
      247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a
      novel low-carbohydrate diet score (LCDS). Physical examination, demographic,
      biochemical and anthropometry parameters were recorded, and the saRHI was
      measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 %
      carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the
      top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v.
      1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients
      with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 =
      1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis
      demonstrated that individuals in the highest LCDS quartile had a significantly
      negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95
      % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern
      characterised by a low amount of carbohydrate, but high amounts of protein and
      fat, is associated with a poorer small artery vascular reactivity in patients
      with increased CV risk.

PMID- 22850318
TI  - The effect of water loading on the urinary ratio of cortisone to cortisol in
      healthy subjects and a new approach to the evaluation of the ratio as an index
      for in vivo human 11beta-hydroxysteroid dehydrogenase 2 activity.
AB  - Factors that give rise to a large variation in the urinary ratio of free
      cortisone to cortisol (UFE/UFF) were investigated to accurately estimate 11beta
      hydroxysteroid dehydrogenase 2 (11beta-HSD2) activity in humans in vivo. A water
      loading test was first carried out in two healthy subjects to examine the effect
      of water intake or urine volume on the urinary ratio of free cortisone to
      cortisol (UFE/UFF). The ratio was found to increase by water loading. We also
      examined urinary concentrations and amounts of cortisol, cortisone, creatinine,
      Na(+), K(+), and Cl(-), and urine volume, as possible factors affecting the
      urinary ratio (UFE/UFF), in 60 urine samples obtained from 15 healthy volunteers.
      Among these factors tested, the urinary concentration of cortisol was most highly
      correlated with the UFE/UFF ratio (r=-0.858), indicating that the in vivo
      activity of 11beta-HSD2 (UFE/UFF) should fluctuate with the changes of the
      urinary concentration of cortisol. Based on the findings, we proposed a new
      estimation method of in vivo activity of 11beta-HSD2 in humans, using the UFE/UFF
      ratio correlated with the urinary concentration of cortisol (UFE/UFF-cortisol
      concentration). Taking into consideration the intra-individual variabilities in
      the urinary concentration of cortisol, there were no significant within-day
      variations in 11beta-HSD2 activity. The findings indicate that 11beta-HSD2
      activities can be accurately evaluated by simply measuring free cortisol and
      cortisone concentrations in spot urine samples. Furthermore, administrations of
      glycyrrhetinic acid in three healthy volunteers were performed to confirm the
      usefulness of the present assessment for the activity of 11beta-HSD2.

PMID- 22850319
TI  - Polyamine conjugates of stigmasterol.
AB  - Three new polyamine conjugates with stigmasterol [(3beta,22E)-stigmasta-5,22-dien
      3-ol] were synthesized and subjected to basic antimicrobial and cytotoxic tests.
      The conjugate derived from spermine, (3beta,22E)-stigmasta-5,22-dien-3-yl 4(12
      amino-4,9-diaza-dodecylamino)-4-oxobutanoate (5c), displayed considerable
      antimicrobial activity on Staphylococcus aureus at low concentration (50 MUg mL(
      1)). The cytotoxic activity was tested on cells of human T-lymfoblastic leukemia
      (IC(50)=35.8 +/- 10.3 MUM (5c) and IC(50)=35.9 +/- 5.7 MUM (5b)) and normal human
      fibroblasts (IC(50)=38.0 +/- 2.8 MUM (5c) and IC(50)=45.5 +/- 1.9 MUM (5b)).
      Conjugate 5a displayed no activity in both tests.

PMID- 22850321
TI  - Temozolomide-related idiosyncratic and other uncommon toxicities:  a systematic
      review.
AB  - Temozolomide (TMZ)-related idiosyncratic and other uncommon toxicities have been
      reported. To better characterize these toxicities and to identify any associated
      risk factors, we performed a systematic review. We searched the PubMed database,
      limited to the English language, published between 1999 and December 2011. We
      selected only those articles in which TMZ was temporally related and was the sole
      or main contributing chemotherapeutic drug to idiosyncratic drug reactions (IDRs)
      and other uncommon toxicities. Hematological IDRs are biopsy-proven aplastic
      anemia or grade V toxicity or grade IV toxicity with slow and incomplete
      hematological recovery. Seventy-three cases were identified, including 21
      hematological IDRs, 31 nonhematological IDRs and uncommon infections, and 21
      second primary cancers. With a caveat of publication and reporting bias, the
      following observations could be made. The hematological IDRs predominantly
      occurred in female patients (exact binomial two-tailed, P=0.0041) and most
      patients were receiving TMZ concomitantly with radiotherapy for glioma. The
      median duration of exposure to TMZ was 30 days and the median cumulative TMZ
      exposure was 2250 mg/m (range, 500-6900 mg/m). The sex predilection was not
      evident in nonhematological IDRs and other uncommon toxicities. TMZ-induced
      pneumonitis and cholestatic hepatitis are emerging as a nonhematological
      hypersensitive reaction and IDR, respectively. For TMZ-related myelodysplasia or
      leukemia, the cumulative dose of TMZ ranged from 1400 to 30 000 mg/m. The
      cumulative dose of TMZ was lower and latency was shorter with a previous exposure
      to other leukemogenic drugs, suggesting that TMZ may have augmented the
      leukemogenic potential of other drugs. Early appearance of profound
      myelosuppression during the course of TMZ and concurrent radiotherapy could be a
      hematological IDR, which warrants prompt investigations to exclude aplastic
      anemia. Myelodysplasia or leukemia developed after a median TMZ exposure of 15
      g/m.

PMID- 22850322
TI  - Reduced cortical call to arms differentiates psychopathy from antisocial
      personality disorder.
AB  - BACKGROUND: Psychopathy and antisocial personality disorder (ASPD) are both
      characterized by impulsive, externalizing behaviors. Researchers have argued,
      however, that psychopathy is distinguished from ASPD by the presence of
      interpersonal-affective features that reflect an underlying deficit in emotional
      sensitivity. No study to date has tested for differential relations of these
      disorders with the brain's natural orienting response to sudden aversive events.
      Method Electroencephalography was used to assess cortical reactivity to abrupt
      noise probes presented during the viewing of pleasant, neutral and unpleasant
      pictures in 140 incarcerated males diagnosed using the Psychopathy Checklist -
      Revised and DSM-IV criteria for ASPD. The primary dependent measure was the P3
      event-related potential response to the noise probes. RESULTS: Psychopaths showed
      significantly smaller amplitude of P3 response to noise probes across trials of
      all types compared with non-psychopaths. Follow-up analyses revealed that this
      overall reduction was attributable specifically to the affective-interpersonal
      features of psychopathy. By contrast, no group difference in general amplitude of
      probe P3 was evident for ASPD versus non-ASPD participants. CONCLUSIONS: The
      findings demonstrate a reduced cortical orienting response to abrupt aversive
      stimuli in participants exhibiting features of psychopathy that are distinct from
      ASPD. The specificity of the observed effect fits with the idea that these
      distinctive features of psychopathy reflect a deficit in defensive reactivity, or
      mobilization of the brain's defensive system, in the context of threat cues.

PMID- 22850323
TI  - Evaluation of the pharmacological function of ulinastatin in experimental
      animals.
AB  - Organ protection is a routine therapy in severe injuries. Our aim was to evaluate
      the beneficial effects of ulinastatin in experimental rats. Rats were randomly
      divided into a sham control, a model control and an ulinastatin-treated group.
      Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined.
      Serum amylase, serum aspartate aminotransaminase (AST), lactate dehydrogenase
      (LDH) and creatine kinase isoenzyme (CKMD) activities, interleukin-8 (IL-8),
      tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and cardiac troponin I
      (nTnl) levels were examined. Results showed that ulinastatin decreased MDA levels
      and ameliorated the down-regulation of SOD activity. In addition, ulinastatin
      pretreatment may decrease serum AST, LDH and CKMD activities, IL-8, TNF-alpha,
      and nTnl levels, and enhance NO level. Our results demonstrated that oxidative
      injury occurred after IR and that ulinastatin exhibits significant protective
      effects against these effects.

PMID- 22850324
TI  - Effects of vitamin D treatment on skeletal muscle histology and ultrastructural
      changes in a rodent model.
AB  - Vitamin D is well known for its role in maintaining calcium and phosphorus
      homeostasis and in promoting bone mineralization; however, more of its
      pleiotropic effects have been described recently. The aim of the present
      investigation was to study the effect of vitamin D treatment on skeletal muscles
      changes under different dietary conditions using an animal model. Four groups of
      C57BL/6J mice (n = 11 each) were maintained on either low fat diet (LFD) or high
      fat diet (HFD) with and without 1alpha,25-dihydroxyvitamin D3 (calcitriol) for 16
      weeks. Animal weigh was recorded at baseline and then regular intervals, and at
      the end of the study, skeletal muscle tissues were harvested for the evaluation
      of the histopathological and ultrastructural changes. When control C57BL/6J mice
      were fed high-fat diet for 12 weeks, body weight gain was significantly increased
      compared with mice fed a LFD. (30.2% vs. 8.4%, p < 0.01). There was a significant
      gradual decrease in the weight of HFD fed mice that were treated with vitamin D
      as compared with a steady increase in the weights of controls (6.8% vs. 28.7%, p
      < 0.01). While the LFD group showed some ultrastructural changes, HDF fed on mice
      showed great muscle structural abnormalities. The whole sarcosome along with its
      membrane and cristae were severely damaged with scattered myocytes in HFD group.
      Furthermore, the mitochondria appeared weak and were on the verge of
      degenerations. The bands were diminished with loss of connections among
      myofibrils. These changes were attenuated in the HFD group treated with vitamin D
      with tissues have regained their normal structural appearance. The current
      findings indicate an important effect of vitamin D on skeletal muscle histology
      under HFD conditions.

PMID- 22850325
TI  - Synthesis of new phosphorus-containing (co)polyesters using solid-liquid phase
      transfer catalysis and product characterization.
AB  - This paper is directed towards the development of safe, and thermally stable
      solid polymer electrolytes. Linear phosphorus-containing (co)polyesters are
      described, including their synthesis, thermal analysis, conductivity, and non
      flammability. Polycondensation of phenylphosphonic dichloride (PPD) with
      poly(ethylene glycol) (PEG 12000) with and without bisphenol A (BA) was carried
      out using solid-liquid phase transfer catalysis. Potassium phosphate is used as
      base. Yields in the range of 85.0-88.0%, and inherent viscosities in the range of
      0.32-0.58 dL/g were obtained. The polymers were characterized by gel permeation
      chromatography, FT-IR, (1)H- and (31)P-NMR spectroscopy and thermal analysis.
      Their flammability was investigated by measuring limiting oxygen index values.
      The polymers are flame retardants and begin to lose weight in the 190  degrees C
      231  degrees C range. Solid phosphorus- containing (co)polyesters were complexed
      with lithium triflate and the resulting ionic conductivity was determined.
      Conductivities in the range of 10(-7)-10(-8) S cm(-1) were obtained.

PMID- 22850326
TI  - The effects of bulking, viscous and gel-forming dietary fibres on satiation.
AB  - The objective was to determine the effects of dietary fibre with bulking, viscous
      and gel-forming properties on satiation, and to identify the underlying
      mechanisms. We conducted a randomised crossover study with 121 men and women.
      Subjects were healthy, non-restrained eaters, aged 18-50 years and with normal
      BMI (18.5-25 kg/m2). Test products were cookies containing either: no added fibre
      (control), cellulose (bulking, 5 g/100 g), guar gum (viscous, 1.25 g/100 g and
      2.5 g/100 g) or alginate (gel forming, 2.5 g/100 g and 5 g/100 g). Physico
      chemical properties of the test products were confirmed in simulated upper
      gastrointestinal conditions. In a cinema setting, ad libitum intake of the test
      products was measured concurrently with oral exposure time per cookie by video
      recording. In a separate study with ten subjects, 4 h gastric emptying rate of a
      fixed amount of test products was assessed by 13C breath tests. Ad libitum energy
      intake was 22 % lower for the product with 5 g/100 g alginate (3.1 (sd 1.6) MJ)
      compared to control (4.0 (sd 2.2) MJ, P< 0.001). Intake of the other four
      products did not differ from control. Oral exposure time for the product with 5
      g/100 g alginate (2.3 (sd 1.9) min) was 48 % longer than for control (1.6 (sd
      0.9) min, P= 0.01). Gastric emptying of the 5 g/100 g alginate product was faster
      compared to control (P< 0.05). We concluded that the addition of 5 g/100 g
      alginate (i.e. gel-forming fibre) to a low-fibre cookie results in earlier
      satiation. This effect might be due to an increased oral exposure time.

PMID- 22850327
TI  - More than words? Hypomanic personality traits, visual imagery and verbal thought
      in young adults.
AB  - The use of visual mental imagery has been proposed to be a risk factor for the
      development of bipolar disorder, due to its potential to amplify affective
      states. This study examined the relation between visual imagery (both trait usage
      and intrusive experiences of such imagery), intrusive verbal thought, and
      hypomania, as assessed by self-report questionnaires, in a sample of young adults
      (N=219). Regression analyses found (after controlling for anxiety, depression,
      and positive and negative affect) that levels of intrusive visual imagery
      predicted levels of hypomania, but that neither trait use of visual imagery nor
      intrusive verbal thought did. These results were consistent with the proposal
      that being a 'visualiser', as opposed to a 'verbaliser', is a risk factor for
      bipolar disorder, with the caveat that it is specifically intrusive experiences
      of imagery, rather than the tendency to utilize imagery per se, that acts as a
      risk factor.

PMID- 22850328
TI  - The characteristics of involuntary and voluntary autobiographical memories in
      depressed and never depressed individuals.
AB  - This study compares involuntary and voluntary autobiographical memories in
      depressed and never depressed individuals. Twenty depressed and twenty never
      depressed individuals completed a memory diary; recording their reactions to 10
      involuntary and 10 voluntary memories over 14-30 days. Psychiatric status
      (Structured Clinical Interview for DSM-IV, SCID-1), psychopathology, rumination
      and avoidance were assessed. For both groups, involuntary memories more
      frequently lead to strong reactions than voluntarily memories. For both modes of
      retrieval, depressed individuals reported more frequent negative reactions than
      never depressed individuals and rated memories as more central to identity with
      higher levels of rumination and avoidance. Depressed individuals retrieved both
      positive and negative memories during involuntary retrieval. These findings
      support the view that involuntary memory retrieval represents a basic mode of
      retrieval during healthy and disordered cognition, and that during depression,
      both involuntary and voluntary memories are central to identity and associated
      with rumination and avoidance.

PMID- 22850329
TI  - Sustained release of heparin on enlarged-pore and functionalized MCM-41.
AB  - Mesoporous silica MCM-41 and SBA-15 were chosen to study the adsorption and
      release of bulky biomolecule heparin, in order to develop new heparin controlled
      delivery system and expand the application of mesoporous materials in life
      science. To explore how the structure of support such as pore size and surface
      state affects the accommodation and release of heparin, we used decane as
      swelling agent to enlarge pores of MCM-41, introduced amino groups for improving
      the biocompatibility of support, and controllably retained templates in the as
      synthesized sample. The influence of modification on the structure of samples was
      investigated by XRD and N(2) adsorption-desorption, whereas their performance of
      adsorbing and releasing heparin was assessed with that of toluidine blue method.
      Both enlarged pore and organic modification significantly promoted the adsorption
      and prolonged the release of heparin in MCM-41, and the release was characterized
      with a three-stage release model. The mechanism of heparin release from
      mesoporous material was studied by fitting the release profiles to the
      theoretical equation. As expected, some mesoporous composites could release
      heparin in the long term with tuned dosage.

PMID- 22850330
TI  - Measuring up to our full potential: physical therapy at the EDGE of best clinical
      practice.

PMID- 22850331
TI  - Coordination tests in persons with acute central nervous system pathology: 
      assessment of interrater reliability and known-group validity.
AB  - BACKGROUND AND PURPOSE: Coordination testing is a standard part of the neurologic
      examination, yet the psychometric properties of many tests used by practitioners
      are unknown. This study investigated the interrater reliability and known-group
      validity of limb coordination tests in participants with acute central nervous
      system (CNS) pathology. METHODS: Twenty-five participants with CNS pathology
      completed 20 different limb coordination tests administered at bedside by a
      physical therapist. Examinations were videotaped and independently rated by a
      neurologist, a physical therapist, and a student physical therapist using a 5
      point ordinal scale. Nine tests were also timed. Results were analyzed for
      interrater reliability and the degree to which they differed between groups
      categorized as having or not having coordination deficits. RESULTS: Participants
      were individuals who had been diagnosed with either a CNS vascular lesion or
      intracranial tumor. Timed test scores had higher levels of agreement (mean
      intraclass correlation coefficient [ICC], 0.69-0.97) than ordinal scores (mean
      kappafree 0.56-0.91). Scores from 5 of the 9 timed measures and 8 of the 20
      ordinal measures differed between groups. DISCUSSION AND CONCLUSIONS: Eleven
      tests were scored reliably between raters (kappa > 0.60 or ICC > 0.75) and were
      performed differently between groups with and without coordination deficits (P <=
      0.05). These tests are recommended for use when examining patients with acute
      neurologic pathology from a vascular lesion or tumor. They are simple to perform
      and require only a stopwatch to complete. Future studies should explore the
      sensitivity and specificity of these tests in disease states and their
      correlation with functional measures.

PMID- 22850333
TI  - A group kickboxing program for balance, mobility, and quality of life in
      individuals with multiple sclerosis:  a pilot study.
AB  - BACKGROUND AND PURPOSE: Balance and mobility impairments are common in
      individuals with multiple sclerosis (MS). The primary purpose of this pilot study
      was to evaluate the feasibility of a 5-week group kickboxing program and to
      measure changes in balance, mobility, and quality of life in individuals with MS
      associated with this training. METHODS: This single-group repeated-measures study
      involved a convenience sample of 15 individuals with MS who had minimal to
      moderate levels of disability and were recruited from the community. Eleven
      participants completed all phases of testing and training. The intervention was a
      5-week group kickboxing program performed 3 times per week. Outcome measures were
      assessed 5 weeks prior to the intervention, 1 week prior to the intervention, and
      within 1 week of completing the intervention. Outcome measures include gait
      speed, Timed Up & Go test, Berg Balance Scale, Dynamic Gait Index, Mini-BESTest,
      Activities Specific Balance Confidence scale, and the Multiple Sclerosis Quality
      of Life Survey. RESULTS: There were significant improvements in gait speed, some
      clinical measures of balance, and balance confidence following the intervention
      but no changes were observed in health-related quality of life. There were no
      unanticipated adverse events and compliance was high. CONCLUSION: Group
      kickboxing appears to be a feasible exercise activity for individuals with MS
      that may lead to improvement in select measures of balance and mobility. However,
      the clinical relevance of these findings is yet to be determined. Further
      investigation of this novel intervention may be warranted.

PMID- 22850334
TI  - Life care planning projections for individuals with motor incomplete spinal cord
      injury before and after locomotor training intervention:  a case series.
AB  - BACKGROUND/PURPOSE: We present a retrospective case series of 2 individuals with
      motor-incomplete spinal cord injury (SCI) to examine differences in lifetime cost
      estimates before and after participation in an intensive locomotor training (LT)
      program. Sections of a life care plan (LCP) were used to determine the financial
      implications associated with equipment, home renovations, and transportation for
      patients who receive LT. An LCP is a viable method of quantifying outcomes
      following any therapeutic intervention. CASE DESCRIPTION: The LCP cases analyzed
      were a 61-year-old woman and a 41/2-year-old boy with motor-incomplete SCI and
      impairments classified by the American Spinal Injury Association Impairment Scale
      (AIS) as AIS D and AIS C, respectively. INTERVENTIONS: Each patient received an
      intensive outpatient LT program 3 to 5 days per week. The 61-year-old woman
      received 198 sessions over 57 weeks and the 41/2-year-old boy received 76
      sessions over 16 weeks. OUTCOMES: The equipment, home renovation, and
      transportation costs of an LCP were calculated before and after LT. Prior to the
      implementation of LT, the 61-year-old woman had estimated lifetime costs between
      $150,247.00 and $199,654.00. Following LT, the estimated costs decreased to
      between $2010.00 and $2446.00 (a decrease of $148,237.00 and $197,208.00).
      Similarly, the 4-year-old boy had estimated lifetime costs for equipment, home
      renovation, and transportation between $535,050.00 and $771,665.00 prior to LT.
      However, the estimated costs decreased to between $97,260.00 and $200,047.00 (a
      decrease of $437,790.00 and $571,618.00) following LT. DISCUSSION: The lifetime
      financial costs associated with equipment, home renovations, and transportation
      following a motor-incomplete SCI were decreased following an intensive LT program
      for the 2 cases presented in this article. The LCP, including costs of
      rehabilitation and long-term medical and personal care costs, may be an effective
      tool to discern cost benefit of rehabilitation interventions.

PMID- 22850337
TI  - Effect of short-duration adaptive servo-ventilation therapy on cardiac function
      in patients with heart failure.
AB  - BACKGROUND: The aim of this study was to investigate whether short-duration
      adaptive servo-ventilation (ASV) therapy improves cardiac function in heart
      failure (HF) patients. METHODS AND RESULTS: Consecutive HF patients (n=86) were
      divided into 3 groups: group A, ASV for a mean of >=4 h; group B, ASV for >=1 to
      <4 h per day; and group C, no ASV or ASV <1 h. The frequency of ASV use did not
      significantly differ between groups A (79.3+/-19.2%) and B (70.9+/-17.4%). After
      6 months, a significant increase in left ventricular ejection fraction (LVEF),
      significant decrease in plasma brain natriuretic peptide (BNP) and decrease in LV
      end-diastolic volume (LVEDV) were observed in groups A (LVEF, 5.0+/-8.1%; BNP, 
      24.9+/-33.7%; LVEDV, -6.2+/-10.1%) and B (LVEF, 3.5+/-5.5%; BNP, -16.5+/-24.6%;
      LVEDV, -5.1+/-8.2%) as compared with group C (LVEF, -1.5+/-6.0%, P=0.004,
      P=0.017; BNP, 2.8+/-10.2%, P=0.002, P=0.017; LVEDV, 0.8+/-9.1%, P=0.031,
      P=0.043). Significant correlation was seen between the total ASV time and changes
      of LVEF (r=0.369, P=0.002), BNP (r=-0.445, P<0.001), and LVEDV (r=-0.374,
      P=0.001). Admission rate was lower in groups A (4.1%) and B (7.1%) than in group
      C (25%, log-rank test; P=0.042, P=0.045). Multivariate analysis showed that the
      frequency of ASV use was a strong parameter for the improvement of LVEF
      (coefficient=0.284, standard error=0.035, P=0.019). CONCLUSIONS: Even a short
      duration of ASV therapy may improve cardiac function in HF patients.

PMID- 22850336
TI  - Relationship between perceived and measured changes in walking after stroke.
AB  - BACKGROUND AND PURPOSE: Examining participant-perceived change in walking
      provides insight into whether changes were meaningful for participants. This
      study examined the relationships between change scores in standardized walking
      outcomes and ratings of perceived change following exercise poststroke. METHODS:
      Self- and fast-paced gait speed and Six-Minute Walk Test (6MWT) distance were
      assessed in 22 participants (age 67 +/- 10.3 years, 1.8 +/- 0.9 years poststroke)
      before and after a 3-month exercise program. Perceived changes were evaluated
      using a 15-point Likert scale. Correlation analyses between measured and
      perceived changes were performed. Subgroups of low and high baseline scores were
      compared for differences in measured and perceived changes. RESULTS: Six-Minute
      Walk Test change was correlated with perceived change (rho = 0.52, P = 0.01),
      greater 6MWT change was demonstrated among participants who perceived improvement
      compared to those who did not (difference 34.4 m, 95% CI: 17.2-51.6, P = 0.04).
      After controlling for measured change, participants with low baseline 6MWT
      distances perceived less change than those who walked high distances at baseline
      (P = 0.006) even when relative change was equivalent. DISCUSSION AND CONCLUSIONS:
      A global rating scale using meaningful and context-specific questions was used to
      determine the relationship between measured and participant-perceived changes in
      6MWT distance. A meaningful difference in 6MWT change was observed between
      participants who did and those who did not perceive improvement. Individuals with
      lower baseline scores may require larger changes in walking distance to perceive
      that a change has occurred. This study contributes to a growing body of evidence
      about the relationships between perceived and measured changes in function and is
      a step in determining thresholds for perceived change in walking after stroke.

PMID- 22850338
TI  - Application of optical coherence tomography in percutaneous coronary
      intervention.
AB  - Optical coherence tomography (OCT) is a high resolution imaging technique that
      offers microscopic visualization of the coronary artery. The fast scanning speed
      and simple imaging procedure of new-generation frequency-domain OCT make this
      technology easy to use in the clinical setting. The OCT examination is useful for
      guidance and risk stratification of percutaneous coronary intervention (PCI). OCT
      derived thin-cap fibroatheroma, which is characterized by large lipid-core and
      thin fibrous cap <65 MUm, is a predictor of peri-PCI complications, such as
      angiographic no-reflow, microvascular obstruction, and post-PCI cardiac troponin
      I elevation. Stent malapposition, tissue protrusion, and stent edge dissection
      are assessed in more detail by OCT than with conventional intravascular imaging
      modalities. Neointimal coverage at strut level assessed by OCT could be a
      surrogate endpoint for quickly scrutinizing safety after drug-eluting stent
      implantation. The OCT findings of in-stent neoatherosclerosis, such as lipid-rich
      neointima, microvascular proliferation, and neointimal plaque rupture, are
      associated with very late stent failure, including thrombosis and restenosis.
      With its excellent ability to assess coronary atherosclerosis and to guide PCI,
      OCT provides new insights into interventional cardiology. 

PMID- 22850340
TI  - Acute toxicity, antinociceptive activity and indole alkaloids of aqueous extract
      from bark of Aspidosperma cuspa (Kunth) Blake.
AB  - ETNOPHARMACOLOGICAL RELEVANCE: Aspidosperma cuspa (Kunth) Blake (Apocynaceae) is
      popularly known as "amargosa" or "cuspa", and its bark is used in folk medicine
      primarily for pain. AIM OF THE STUDY: In the present study the acute toxicity,
      antinociceptive effect and alkaloids of the aqueous decoction extract of the
      Aspidosperma cuspa bark in mice was investigated. MATERIALS AND METHODS: Acute
      toxicity was tested using a variation of the method described by Lichfield and
      Wilcoxon. The antinociceptive activity was evaluated using the acetic acid
      induced writhing and tail-flick tests. The phytochemical analysis was performed.
      RESULTS AND CONCLUSION: Oral administration of the extract did not cause animal
      death (LD(50)>4 g/kg), and the histological analysis showed an absence of
      alterations in all organs examined. TD(50) of the extract was 0.5521 g/kg for
      male mice and 1.1565 g/kg for females. The aqueous extract at doses 276 mg/kg
      (p.o.) did not produce a significant inhibition of acetic acid-induced writhes,
      but showed a significant effect in tail-flick test. Naloxone, an opioid receptor
      antagonist, pretreatment inhibited significantly the antinociceptive activity of
      the extract. It is suggested that the aqueous decoction extract of the bark of
      Aspidosperma cuspa has an antinociceptive effect, and this may be mediated by
      opioid receptors. Three indole alkaloids (aspidocarpine, 11-methoxytubotaiwine
      and picraline) were isolated from the aqueous extract. The antinociceptive
      activity of the extract is presumed to be due to these compounds.

PMID- 22850339
TI  - Normal vascular function as a prerequisite for the absence of coronary
      calcification in patients free of cardiovascular disease and diabetes.
AB  - BACKGROUND: The absence of coronary artery calcium (CAC) is a marker of very low
      cardiovascular risk. Endothelial cells may have an effect on the initiation and
      propagation of arterial calcification. We aimed to identify the relationship
      between the absence of CAC and endothelial function in individuals without
      cardiovascular disease and diabetes. METHODS AND RESULTS: CAC was assessed using
      electron-beam computed tomography and the calcium score was then computed.
      Endothelial function was measured by assessing reactive hyperemia-induced
      vasodilation and expressed by the reactive hyperemia index (RHI). Of 82 patients,
      39 had non-detectable calcium (CAC score=0) and 43 had a CAC score >0. In the CAC
      score=0 group, the prevalence of normal endothelial function was 84.6%, compared
      to 48.8% in the CAC score >0 group, P=0.001. The absence of CAC was highly
      correlated with normal endothelial function (gamma=0.704, P<0.001). On average,
      endothelial function was significantly better in the CAC score=0 group than in
      the CAC score >0 group (RHI 2.2+/-0.6 vs. 1.8+/-0.5, P=0.002). In a multivariate
      logistic regression model, only normal endothelial function (odds ratio [OR]
      5.03, 95% confidence interval [CI] 1.55-16.27, P=0.007) and age (years) (OR 0.91,
      95% CI 0.86-0.96, P=0.002) were independently associated with the absence of CAC.
      CONCLUSIONS: Normal functional status of the vasculature may be important for the
      prevention of coronary calcification and may partly account for the low
      cardiovascular risk of absent CAC.

PMID- 22850341
TI  - Thermoelectric probe for the Rashba spin-orbit interaction strength in a two
      dimensional electron gas.
AB  - The thermoelectric coefficients of a two dimensional electron gas (2DEG) with the
      Rashba spin-orbit interaction (SOI) are presented here. In the absence of a
      magnetic field, thermoelectric coefficients are enhanced due to the Rashba SOI.
      In the presence of a magnetic field, the thermoelectric coefficients of spin-up
      and spin-down electrons oscillate with different frequencies and produces beating
      patterns in the components of the total thermoelectric power and the total
      thermal conductivity. We also provide analytical expressions for the
      thermoelectric coefficients to explain the formation of the beating pattern. We
      obtain a simple relation which determines the strength of the Rashba SOI if the
      magnetic fields corresponding to any two successive beat nodes are known from the
      experiment.

PMID- 22850345
TI  - Nausea and vomiting treatment after surgery: we still can do better.

PMID- 22850346
TI  - Case scenario:  perioperative administration of tocotrienols and green tea
      extract in a child with familial dysautonomia.

PMID- 22850344
TI  - Exploring the relationship between perceptual learning and top-down attentional
      control.
AB  - Here, we review the role of top-down attention in both the acquisition and the
      expression of perceptual learning, as well as the role of learning in more
      efficiently guiding attentional modulations. Although attention often mediates
      learning at the outset of training, many of the characteristic behavioral and
      neural changes associated with learning can be observed even when stimuli are
      task irrelevant and ignored. However, depending on task demands, attention can
      override the effects of perceptual learning, suggesting that even if top-down
      factors are not strictly necessary to observe learning, they play a critical role
      in determining how learning-related changes in behavior and neural activity are
      ultimately expressed. In turn, training may also act to optimize the
      effectiveness of top-down attentional control by improving the efficiency of
      sensory gain modulations, regulating intrinsic noise, and altering the read-out
      of sensory information.

PMID- 22850348
TI  - Creating defined gaseous environments to study the effects of hypoxia on C.
      elegans.
AB  - Oxygen is essential for all metazoans to survive, with one known exception.
      Decreased O(2) availability (hypoxia) can arise during states of disease, normal
      development or changes in environmental conditions. Understanding the cellular
      signaling pathways that are involved in the response to hypoxia could provide new
      insight into treatment strategies for diverse human pathologies, from stroke to
      cancer. This goal has been impeded, at least in part, by technical difficulties
      associated with controlled hypoxic exposure in genetically amenable model
      organisms. The nematode Caenorhabditis elegans is ideally suited as a model
      organism for the study of hypoxic response, as it is easy to culture and
      genetically manipulate. Moreover, it is possible to study cellular responses to
      specific hypoxic O(2) concentrations without confounding effects since C. elegans
      obtain O(2) (and other gasses) by diffusion, as opposed to a facilitated
      respiratory system. Factors known to be involved in the response to hypoxia are
      conserved in C. elegans. The actual response to hypoxia depends on the specific
      concentration of O(2) that is available. In C. elegans, exposure to moderate
      hypoxia elicits a transcriptional response mediated largely by hif-1, the highly
      conserved hypoxia-inducible transcription factor. C .elegans embryos require hif
      1 to survive in 5,000-20,000 ppm O(2). Hypoxia is a general term for "less than
      normal O(2)". Normoxia (normal O(2)) can also be difficult to define. We
      generally consider room air, which is 210,000 ppm O(2) to be normoxia. However,
      it has been shown that C. elegans has a behavioral preference for O(2)
      concentrations from 5-12% (50,000-120,000 ppm O(2)). In larvae and adults, hif-1
      acts to prevent hypoxia-induced diapause in 5,000 ppm O(2). However, hif-1 does
      not play a role in the response to lower concentrations of O(2) (anoxia,
      operational definition <10 ppm O(2)). In anoxia, C. elegans enters into a
      reversible state of suspended animation in which all microscopically observable
      activity ceases. The fact that different physiological responses occur in
      different conditions highlights the importance of having experimental control
      over the hypoxic concentration of O(2). Here, we present a method for the
      construction and implementation of environmental chambers that produce reliable
      and reproducible hypoxic conditions with defined concentrations of O(2). The
      continual flow method ensures rapid equilibration of the chamber and increases
      the stability of the system. Additionally, the transparency and accessibility of
      the chambers allow for direct visualization of animals being exposed to hypoxia.
      We further demonstrate an effective method of harvesting C. elegans samples
      rapidly after exposure to hypoxia, which is necessary to observe many of the
      rapidly-reversed changes that occur in hypoxia. This method provides a basic
      foundation that can be easily modified for individual laboratory needs, including
      different model systems and a variety of gasses.

PMID- 22850347
TI  - MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in
      schizophrenia patients with marijuana misuse.
AB  - BACKGROUND: Adolescent marijuana use is associated with increased risk for
      schizophrenia. We previously reported that marijuana misuse in conjunction with
      specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele
      carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia
      patients. In this study, we assessed the influence of another cannabinoid-related
      gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14-CNR1
      gene-gene interactions in conferring brain volume abnormalities among
      schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member
      of the MAPK family involved in diverse cellular processes, including CNR1-induced
      apoptosis. METHOD: We genotyped 235 schizophrenia patients on nine MAPK14 tag
      single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample
      had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain
      volumes across patients with versus without marijuana abuse/dependence were
      examined using ANCOVA. RESULTS: Of the MAPK14 tSNPs, only rs12199654 had
      significant genotype effects and genotype * marijuana misuse interaction effects
      on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had
      significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14
      rs12199654 on WM volume deficits remained significant even after controlling for
      the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14
      CNR1 diplotype and diplotype * marijuana interaction on WM brain volumes, with
      both genetic variants having additive contributions to WM volume deficits only in
      patients with marijuana misuse. CONCLUSIONS: Given that CNR1-induced apoptosis is
      preceded by increased MAPK phosphorylation, our study suggests that potential
      MAPK14-CNR1 gene-gene interactions may mediate brain morphometric features in
      schizophrenia patients with heavy marijuana use.

PMID- 22850350
TI  - Reducing total health burden from 2001 to 2009: an employer counter-trend success
      story and its implications for health care reform.
AB  - OBJECTIVES: To examine total health burden for an employer whose health-related
      focus is direct and indirect costs. To explore implications for the Final Rule
      for Accountable Care Organizations recently issued by the Centers for Medicare
      and Medicaid Services, whose focus includes direct but not indirect costs.
      METHODS: Used 42 claims and survey-based measures to track this employer's
      continental US workforce burden in the aggregate and by healthy and selected
      disease designations from 2001-2002 to 2008-2009. RESULTS: Starting from
      equivalent baselines, this employer's aggregate total direct costs decreased 16%
      (8.5% adjusted) whereas comparable US per capita expenditures rose 22.1%. Even
      larger decreases were recorded in total indirect costs. The healthy and disease
      designations replicated this pattern. Minimal employee cost shifting occurred.
      CONCLUSIONS: Attention to direct and indirect costs helped put this employer's
      health care investment on a markedly more sustainable path than comparable
      national cost trends. Fully tapping the applicable lessons this and other
      purchasers have learned will be facilitated by amending the Final Rule to include
      measures of indirect costs.

PMID- 22850349
TI  - Employer-mandated sleep apnea screening and diagnosis in commercial drivers.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) is common among commercial drivers
      and associated with health/safety risks, leading several trucking firms to
      mandate OSA screening. METHODS: A total of 19,371 commercial drivers were
      screened for OSA with an online questionnaire (Somni-Sage reg) through employer
      mandates. Questionnaire and polysomnography results were analyzed
      retrospectively. RESULTS: Screening categorized 5908 drivers (30%) as higher
      risk. To date, employers have sent 2103 higher-risk drivers for polysomnography,
      demonstrating that 68% of high-risk drivers tested had an apnea-hypopnea index
      (AHI) greater than 10 and 80% had an AHI of 5 or more. A conservative prevalence
      estimate for OSA (AHI > 10) was 21% among the drivers studied. CONCLUSIONS:
      Online screening followed by polysomnography for high-risk drivers demonstrates
      as many as 21% of commercial drivers may have OSA. Mandatory screening can have a
      high yield among commercial drivers.

PMID- 22850351
TI  - Induced sputum, exhaled NO, and breath condensate in occupational medicine.
AB  - OBJECTIVE: Studies of fractional exhaled NO (FeNO) or induced sputum are now well
      standardized and the exponential increase in publications about exhaled breath
      condensate reflects growing interest in a noninvasive diagnosis of pulmonary
      diseases in occupational medicine. METHODS: This review describes current
      techniques (FeNO, induced sputum, and exhaled breath condensate) for the study of
      inflammation and oxidative stress biomarkers. RESULTS: These biomarkers are FeNO,
      cytokines, H2O2, 8-isoprostane, malondialdehyde, and nitrogen oxides. These
      techniques also include the study of markers of the toxic burden in the lungs
      (heavy metals and mineral compounds) that are important in occupational health
      exposure assessment. CONCLUSIONS: In occupational medicine, the study of both
      volatile and nonvolatile respiratory biomarkers can be useful in medical
      surveillance of exposed workers, the early identification of respiratory
      diseases, or the monitoring of their development.

PMID- 22850352
TI  - Imputing at-work productivity loss using results of a randomized controlled trial
      comparing tapentadol extended release and oxycodone controlled release for
      osteoarthritis pain.
AB  - OBJECTIVE: : To determine the impact of tapentadol extended release (ER) versus
      placebo or oxycodone controlled release (CR) on the work productivity of adults
      with chronic moderate to severe knee osteoarthritis pain. METHODS: : Using
      clinical trial data on pain outcomes, a validated methodology imputed treatment
      group differences in at-work productivity and associated differences in
      productivity costs (assuming a $100,000 annual salary per participant). RESULTS:
      : Imputed improvements in at-work productivity were significantly greater for
      tapentadol ER compared with either placebo (mean, 1.96% vs 1.51%; P = 0.001) or
      oxycodone CR (mean, 1.96% vs 1.40%; P < 0.001). Mean net savings per participant
      were $450 (P < 0.01) for tapentadol ER versus placebo and $560 (P = 0.001) for
      tapentadol ER versus oxycodone CR. CONCLUSION: : Effective osteoarthritis pain
      treatment also may help employees to function better at work and reduce their
      employers' productivity costs.

PMID- 22850353
TI  - Barriers and facilitators to implementation of an occupational health guideline
      aimed at preventing weight gain among employees in the Netherlands.
AB  - OBJECTIVE: To assess barriers and facilitators to implementation of an
      occupational health guideline aimed at preventing weight gain. METHODS: Barriers
      and facilitators to implementation were assessed among 14 occupational physicians
      (OPs) and employers and analyzed following a systematic approach using Atlas.ti.
      RESULTS: Barriers and facilitators mentioned by OPs and employers were related to
      the sociopolitical context, organization, OP, and guideline. Recommendations
      include the formation of a linkage group, collaboration with other experts,
      formation of peer support groups, and communicating benefits of investments,
      expectations, and ethical considerations. Results of this study recommend
      incorporating these barriers and facilitators in the guideline, including
      strategies about how to overcome barriers and stimulate facilitators.
      CONCLUSIONS: The identified barriers and facilitators can be used to increase the
      chance of successful implementation of the final guideline into occupational
      health practices throughout the Netherlands.

PMID- 22850354
TI  - Bronchodilator activity of the selective muscarinic antagonist revatropate in
      horses with heaves.
AB  - Bronchodilators are frequently used to attenuate airway obstruction in equine
      heaves (or recurrent airway obstruction). This study evaluated the selective
      (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential
      advantages over non-specific antimuscarinic agents such as ipratropium. Protocol
      1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded,
      negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and
      2mg) controlled, dose escalation study, with six heaves horses. The lowest doses
      of revatropate and ipratropium induced a rapid (within 1h) and significant
      improvement in airway function. The highest doses of both drugs had no
      significant effect on gastrointestinal sound score or iris function, but resulted
      in tacky mucous membranes and reduced gastrointestinal sound score in some
      horses. In Protocol 2, a cross-over design comparing the duration of action of
      inhaled revatropate (1mg), ipratropium (0.3mg) and saline, some indices of airway
      function were improved for between 5 and 6h after revatropate administration, and
      for between 6 and 24h after ipratropium administration. Inhaled revatropate and
      ipratropium had similar effects on airway function, with no significant
      difference between their efficacies. Importantly, however, only revatropate
      significantly improved clinical scores of breathing effort, improving combined
      clinical score at the 1h time point and abdominal score at the 1-3h time points.
      No significant adverse events were observed in Protocol 2, although some horses
      had reduced gastrointestinal sound scores. Inhaled revatropate is therefore a
      safe and effective bronchodilator for treating airway obstruction in heaves.

PMID- 22850355
TI  - The compressibility of high purity YbB2.
AB  - The compressibility and phase stability of Y bB(2) are investigated under high
      pressure using high-resolution synchrotron x-ray diffraction in a diamond anvil
      cell. The bulk modules of high purity Y bB(2) is obtained as ~182 GPa using the
      Birch-Murnaghan equation of state. The patterns measured up to 20 GPa and the
      pressure dependence of normalized lattice parameters, a/a(0) and c/c(0), reveal
      that the compressibility of Y bB(2) is low and fairly isotropic, and this
      material can be classified as a hard material. X-ray photoemission studies
      demonstrate that Yb in Y bB(2) has a mostly trivalent valence state at room
      temperature. Moreover, sample preparation details provide a new insight into the
      high purity synthesis of Y bB(2) at ambient pressure and moderate temperatures.
      The presented structural and compressibility results are in agreement with the
      available theoretical and experimental data on binary rare-earth borides and can
      serve as a reliable reference for future studies.

PMID- 22850356
TI  - RCM: a novel association approach to search for coronary artery disease genetic
      related metabolites based on SNPs and metabolic network.
AB  - Integration of genetic and metabolic network holds promise for providing insight
      into human disease. Coronary artery disease (CAD) is strongly heritable, but the
      heritability of metabolic compounds has not been evaluated in human metabolic
      context. Here we performed a genetic-based computational approach within eight
      sub-cellular networks from Edinburgh Human Metabolic Network to identify
      significant genetic risk compounds (SGRCs) of CAD. Our results provide the
      evidence that the high heritabilities of SGRCs played an important role in CAD
      pathogenesis. Besides, SGRCs were discovered to be strongly associated with lipid
      metabolism. We also established a possible disease-causing reference table to
      decipher genetic associations of SGRCs with CAD. Comparing with traditional
      method, RCM experienced better performance in CAD genetic risk compounds'
      identification. These findings provided novel insights into CAD pathogenesis from
      a genetic perspective.

PMID- 22850357
TI  - Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese
      hypertensive patients aged 45-75 years.
AB  - We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma
      homocysteine (tHcy) >= 10 MUmol/l) and its major determinants in rural Chinese
      hypertensive patients. A cross-sectional investigation was carried out in
      Lianyungang of Jiangsu province, China. This analysis included 13 946
      hypertensive adults. The prevalence of hyperhomocysteinaemia was 51.6 % (42.7 %
      in women and 65.6 % in men). The OR of hyperhomocysteinaemia were 1.52 (95 % CI
      1.39, 1.67) and 2.32 (95 % CI 2.07, 2.61) for participants aged 55-65 and 65-75
      v. 45-55 years; 1.27 (95 % CI 1.18, 1.37) for participants with a BMI >= 25 v. <
      25 kg/m2; 1.14 (95 % CI 1.06, 1.23) for participants with v. without
      antihypertensive treatment; 1.09 (95 % CI 1.00, 1.18) for residents inland v.
      coastal; 0.89 (95 % CI 0.82, 0.97) and 0.83 (95 % CI 0.74, 0.92) for participants
      with moderate and high v. low physical activity levels; 1.54 (95 % CI 1.41, 1.68)
      and 2.47 (95 % CI 2.17, 2.81) for participants with a glomerular filtration rate
      60-90 and < 60 v. >= 90 ml/min per 1.73 m2; and 1.20 (95 % CI 1.07, 1.35) and
      3.81 (95 % CI 3.33, 4.36) for participants with CT and TT v. CC genotype at
      methylenetetrahydrofolate reductase 677C>T polymorphism, respectively.
      Furthermore, higher tHcy concentrations were observed in smokers of both sexes
      (men: geometric mean 12.1 (interquartile range (IQR) 9.2-14.5) v. 11.9 (IQR 9.
      14.) MUmol/l, P= 0.005; women: geometric mean 10.3 (IQR 8.3-13.0) v. 9.6 (IQR 7.8
      11.6) MUmol/l, P= 0.010), and only in males with hypertension grade 3 (v. grade 1
      or controlled blood pressure) (geometric mean 12.1 (IQR 9.2-14.4) v. 11.7 (IQR
      9.2-14.0), P= 0.016) and in male non-drinkers (yes v. no) (geometric mean 12.3
      (IQR 9.4-14.8) v. 11.7 (IQR 9.1-13.9), P= 0.014). In conclusion, there was a high
      prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly
      in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as
      folic acid supplementation and lifestyle change.

PMID- 22850358
TI  - Effect of intermittent preventive treatment for malaria during infancy on
      serological responses to measles and other vaccines used in the Expanded
      Programme on Immunization: results from five randomised controlled trials.
AB  - BACKGROUND: Intermittent preventive treatment for malaria during infancy (IPTi)
      is the administration of a full therapeutic course of antimalarial drugs to
      infants living in settings where malaria is endemic, at the time of routine
      vaccination in the first year of life. We investigated whether IPTi with
      sulfadoxine-pyrimethamine or other antimalarial drug combinations adversely
      affected serological responses to vaccines used in the Expanded Programme on
      Immunization (EPI). METHODS: The study was done in a subset of children enrolled
      in five randomised controlled trials in Navrongo, Ghana; Kilimanjaro, Tanzania;
      Manhica, Mozambique; Kisumu, Kenya; and Bungoma, Kenya. All infants presenting
      for the second dose of the diphtheria-tetanus-pertussis vaccination (given at 8
      10 weeks of age) were eligible, and analyses included all children who had
      received measles vaccination (at 9 months of age) and at least one dose of IPTi
      or placebo. Blood samples were collected before and after vaccination, and
      antibody titres were measured by plaque reduction neutralisation (measles, yellow
      fever), microneutralisation (polio serotypes 1 and 3), and ELISA (all other EPI
      antigens). Laboratory personnel were unaware of the randomisation groups. We
      compared the proportion of infants in the IPTi and placebo groups who did not
      attain protective antibody titres after vaccination, using a one-sided
      significance non-inferiority margin of 5% for measles (the primary endpoint) and
      10% for other EPI antigens. FINDINGS: Between September, 2000, and May, 2008,
      8416 children were enrolled in the five studies. Paired samples from 2368
      children from sites where sulfadoxine-pyrimethamine was compared with placebo
      were analysed for measles antibodies. 464 children with detectable measles
      antibody in their sample before vaccination were excluded, leaving 1904
      individuals (934 placebo and 970 sulfadoxine-pyrimethamine) in the study. IPTi
      with sulfadoxine-pyrimethamine did not have a clinically significant effect on
      immune responses to measles vaccine; 61 of 970 (6.3%) children who received IPTi
      did not develop a protective antibody response after measles vaccination compared
      with 60 of 934 (6.4%) who received placebo, a difference of -0.14% (95% CI -2.3
      to 2.1). When other antimalarial drugs were used for IPTi the results were much
      the same. Among 2396 children from whom serological response data for other EPI
      antigens were available, we identified no evidence of an adverse effect of IPTi
      with sulfadoxine-pyrimethamine or other antimalarial drugs on the proportion
      achieving protective antibody concentrations. INTERPRETATION: IPTi with
      sulfadoxine-pyrimethamine does not affect serological responses to EPI vaccines.
      This analysis, therefore, supports the WHO recommendation for coadministration of
      IPTi with sulfadoxine-pyrimethamine to infants at the time of the second and
      third doses of DTP and measles vaccination, in areas of sub-Saharan Africa with
      moderate to high malaria transmission and where malaria parasites are sensitive
      to these drugs. It also suggests that treatment of clinical malaria at or around
      the time of vaccination does not compromise vaccine responsiveness. FUNDING: Bill
      & Melinda Gates Foundation.

PMID- 22850359
TI  - Does IPTi decrease malaria morbidity but not mortality?

PMID- 22850360
TI  - Bi-hemispheric effects on corticospinal excitability induced by repeated sessions
      of imagery versus observation of actions.
AB  - PURPOSE: To investigate whether repeated sessions of motor imagery and action
      observation modulate corticospinal excitability (CE) over time, whether these
      processes are susceptible of any training effect and if such effect might be
      different for the dominant and non dominant hemisphere. METHODS: 11 subjects
      underwent three sessions, spaced 5-7 days, of single-pulse Transcranial Magnetic
      Stimulation (TMS) of right and left primary motor cortex. Subjects were asked to
      imagine or observe pinch-grip actions with either hand. Motor evoked potentials
      (MEPs) were recorded bilaterally from the First Dorsal Interosseus muscle (FDI),
      acting as main agonist during precision grip. RESULTS: Motor imagery consistently
      enhanced CE with respect to action observation, regardless of hemispheric
      lateralization and of separate testing sessions. However, motor imagery increased
      CE only when measured over the non-dominant hemisphere, during the third session
      with respect to the first one. The increase of CE induced by action observation
      in the first session was not further modified throughout the remaining two
      sessions, in either hemisphere. CONCLUSIONS: Results suggest that motor imagery
      is sustained by a cortical network susceptible to training effects only for the
      non-dominant hemisphere. Such an effect was lacking for action observation,
      likely because of the innateness of these mechanisms. Results might have
      implications for rehabilitative purposes.

PMID- 22850361
TI  - Implementation of the fifth link of the chain of survival concept for out-of
      hospital cardiac arrest.
AB  - BACKGROUND: The American Heart Association 2010 resuscitation guidelines
      recommended adding a fifth link (multidisciplinary postresuscitation care in a
      regional center) to the previous 4 in the chain of survival concept for out-of
      hospital cardiac arrest. Our study aimed to determine the effectiveness of this
      fifth link. METHODS AND RESULTS: This multicenter prospective cohort study
      involved all eligible out-of-hospital cardiac arrest patients in the Aizu region
      (n=1482, suburban/rural, Fukushima, Japan). Proportions of favorable neurological
      outcomes were evaluated before (January 2006-April 2008) and after (January 2009
      December 2010) the implementation of the fifth link. After implementation, all
      patients were transported directly from the field to the tertiary-level hospital
      or secondarily from an outlying hospital to the tertiary-level hospital after
      restoration of circulation. The tertiary hospital provided intensive
      postresuscitation care, including appropriate hemodynamic and respiratory
      management, therapeutic hypothermia, and percutaneous coronary intervention. One
      month survival with a favorable neurological outcome among all patients treated
      by emergency medical services providers improved significantly after
      implementation (4 of 770 [0.5%] versus 21 of 712 [3.0%]; P<0.001). The adjusted
      odds ratios of favorable neurological outcome were 0.9 (95% confidence interval,
      0.7-1.1) for early access to emergency medical care, 3.1 (95% confidence
      interval, 0.7-14.2) for bystander resuscitation, 14.7 (95% confidence interval,
      3.2-67.0) for early defibrillation, 1.0 (95% confidence interval, 1.0-1.1) for
      early advanced life support, and 7.8 (95% confidence interval, 1.6-39.0) for the
      fifth link. CONCLUSION: The proportion of out-of-hospital cardiac arrest patients
      with a favorable neurological outcome improved significantly after the
      implementation of the fifth link, which may be an independent predictor of
      outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.apps.who.int/trialsearch.
      Unique identifier: UMIN000001607.

PMID- 22850362
TI  - Women and coronary heart disease: a century after Herrick: understudied,
      underdiagnosed, and undertreated.

PMID- 22850363
TI  - Hot-air balloon explosion in the heart.

PMID- 22850364
TI  - Multiparametric cardiovascular magnetic resonance assessment of pacemaker-induced
      alterations in ventricular activation and function.

PMID- 22850365
TI  - Cardiology patient page. Warfarin management: international normalized ratio self
      testing and warfarin self-dosing.

PMID- 22850367
TI  - Letter by Moody et al regarding article "Prevalence and significance of
      alterations in cardiac structure and function in patients with heart failure and
      a preserved ejection fraction".

PMID- 22850368
TI  - Letter by Romanelli et al regarding article, "Prevalence and significance of
      alterations in cardiac structure and function in patients with heart failure and
      a preserved ejection fraction".

PMID- 22850369
TI  - Factors influencing the microbial safety of fresh produce: a review.
AB  - Increased consumption, larger scale production and more efficient distribution of
      fresh produce over the past two decades have contributed to an increase in the
      number of illness outbreaks caused by this commodity. Pathogen contamination of
      fresh produce may originate before or after harvest, but once contaminated
      produce is difficult to sanitize. The prospect that some pathogens invade the
      vascular system of plants and establish "sub-clinical" infection needs to be
      better understood to enable estimation of its influence upon risk of human
      illness. Conventional surface sanitation methods can reduce the microbial load,
      but cannot eliminate pathogens if present. Chlorine dioxide, electrolyzed water,
      UV light, cold atmospheric plasma, hydrogen peroxide, organic acids and acidified
      sodium chlorite show promise, but irradiation at 1 kGy in high oxygen atmospheres
      may prove to be the most effective means to assure elimination of both surface
      and internal contamination of produce by pathogens. Pathogens of greatest current
      concern are Salmonella (tomatoes, seed sprouts and spices) and Escherichia coli
      O157:H7 on leafy greens (spinach and lettuce). This review considers new
      information on illness outbreaks caused by produce, identifies factors which
      influence their frequency and size and examines intervention effectiveness.
      Research needed to increase our understanding of the factors influencing
      microbial safety of fresh produce is addressed.

PMID- 22850370
TI  - Controlled fermentation of kimchi using naturally occurring antimicrobial agents.
AB  - Kimchi is a traditional Korean fermented food. Since it ferments continuously
      during distribution and storage, the extension of shelf life by preventing over
      acidification is a major concern in the kimchi industry. One of the most
      frequently attempted ways to delay fermentation is to add naturally occurring
      antimicrobial agents. Many researchers have investigated ways to delay over
      acidification by adding minor ingredients, fruits or fruit seed extracts,
      extracts of medicinal herbs, culinary herbs and spices, and other miscellaneous
      substances to kimchi. The addition of naturally occurring antimicrobial agents
      may enhance the acceptability of kimchi to consumers over a longer period of time
      but may also have a disadvantage in that it may cause changes in sensory quality,
      especially if added in large amounts. To avoid undesirable sensory changes,
      application of hurdle technologies (i.e., multifactor preservative systems) which
      involve using combinations of low amounts of various naturally occurring
      antimicrobial agents as ingredients should be explored with the goal of
      controlling fermentation. If synergistic or additive antimicrobial effects can be
      achieved using small amounts of a combination of natural agents, changes in
      sensory qualities will be minimized, thereby prolonging shelf life. Research
      findings summarized in this review provide a basis for developing effective
      hurdle technologies using naturally occurring antimicrobial agents to extend
      shelf life of kimchi and perhaps other types of traditional fermented foods.

PMID- 22850371
TI  - Prevalent lactic acid bacteria in cider cellars and efficiency of Oenococcus oeni
      strains.
AB  - Malolactic fermentation (MLF) is an important step in cider production in order
      to allowing for improvement of microbiological stability and organoleptic
      characteristics of cider. Induction of this fermentation by using starter
      cultures enables a better control over this bioprocess, but although it is a
      common practice in winemaking, starters specifically focussed for cider MLF are
      not yet commercially available. Proper starter cultures need to present the
      ability to degrade l-malic acid conferring pleasing sensory characteristics while
      avoiding toxicological risks. In this work, lactic acid bacteria (LAB) were first
      isolated from MLF industrial cider samples, obtained in a cellar in the main
      cider-producing region of Spain, Asturias. Isolates, identified by molecular
      tools, belonged to the Lactobacillus brevis and Oenococcus oeni species. After a
      phylogenetic analysis, representative strains of both identified species were
      evaluated in order to determine their fermentation capacity, showing O. oeni the
      best behaviour in this cider fermentation, as previously demonstrated for wine in
      the literature. Consequently, and with the aim to test the influence at strain
      level, selection of O. oeni isolates as starters for cider fermentation has been
      undergone. In order to check the influence of geography over biodiversity, O.
      oeni strains from six different industrial cellars representing the distinct
      producing areas in the region (located in a ratio of 30 km) were analyzed by
      using a specific RAPD method. In this way, isolates were typed in five distinct
      groups, mainly corresponding to each producing area. All strains isolated from
      the same cellar showed the same RAPD profile revealing the significance of
      geographical origin in the indigenous cider LAB. Molecular tools were applied to
      reject those isolates exhibiting presence of genes related to organoleptic
      spoilage (exopolysaccharides and acrolein production) or food safety (biogenic
      amine production), as key selection criteria. Representative strains of each of
      the five O. oeni RAPD groups were tested as pure cultures to evaluate their
      technological utility for cider production. Experimental data of malic acid
      degradation and cell concentration obtained were fitted to previously selected
      kinetic models aimed to optimization and prediction of bioprocess performance.
      Four strains revealed as suitable potential starter cultures for conducting MLF
      in cider production.

PMID- 22850372
TI  - Application of bacteriocinogenic Enterococcus mundtii CRL35 and Enterococcus
      faecium ST88Ch in the control of Listeria monocytogenes in fresh Minas cheese.
AB  - Several strains of Enterococcus spp. are capable of producing bacteriocins with
      antimicrobial activity against important bacterial pathogens in dairy products.
      In this study, the bacteriocins produced by two Enterococcus strains
      (Enterococcus mundtii CRL35 and Enterococcus faecium ST88Ch), isolated from
      cheeses, were characterized and tested for their capability to control growth of
      Listeria monocytogenes 426 in experimentally contaminated fresh Minas cheese
      during refrigerated storage. Both strains were active against a variety of
      pathogenic and non-pathogenic microorganisms and bacteriocin absorption to
      various L. monocytogenes, Enterococcus faecalis ATCC 19443 and Lactobacillus
      sakei ATCC 15521 varied according to the strain and the testing conditions (pH,
      temperature, presence of salts and surfactants). Growth of L. monocytogenes 426
      was inhibited in cheeses containing E. mundtii CRL35 up to 12 days at 8  degrees
      C, evidencing a bacteriostatic effect. E. faecium ST88Ch was less effective, as
      the bacteriostatic affect occurred only after 6 days at 8  degrees C. In cheeses
      containing nisin (12.5 mg/kg), less than one log reduction was observed. This
      research underlines the potential application of E. mundtii CRL35 in the control
      of L. monocytogenes in Minas cheese.

PMID- 22850373
TI  - Adhesion of human pathogenic enteric viruses and surrogate viruses to inert and
      vegetal food surfaces.
AB  - Enteric viruses, particularly human Noroviruses (NoV) and hepatitis A virus
      (HAV), are key food-borne pathogens. The attachment of these pathogens to
      foodstuff and food-contact surfaces is an important mechanism in the human
      contamination process. Studies were done to investigate the nature of the
      physicochemical forces, such as hydrophobic and electrostatic ones, involved in
      the interaction virus/matrix but, at this day, only few data are available
      concerning surface properties of viruses and prediction of the adhesion capacity
      of one specific virus onto matrices is still very difficult. The purpose of this
      study was to propose a reference system, including a representative virus
      surrogate, able to predict as close as possible behaviour of pathogenic viruses
      in term of adhesion on inert (stainless steel and polypropylene) and food
      surfaces (lettuce leaves, strawberries and raspberries). The adhesion of human
      pathogenic enteric viruses, cultivable strain of HAV and non-cultivable strains
      of human NoV (genogroups I and II), have been quantified and compared to these of
      human enteric viruses surrogates, included the MNV-1 and three F-specific RNA
      bacteriophages (MS2, GA and Qbeta). A standardized approach was developed to
      assess and quantify viral adhesion on tested matrices after a contact time with
      each virus using real-time RT-PCR. Methods used for virus recovery were in
      accordance with the CEN recommendations, including a bovine Enterovirus type 1 as
      control to monitor the efficiency of the extraction process and amplification
      procedure from directly extracted or eluted samples. The adhesion of human
      pathogenic viruses, ranging from 0.1 to 2%, could be comparable for all matrices
      studied, except for NoV GII on soft fruits. Adhesion percentages obtained for the
      studied surrogate virus and phages were shown to be comparable to those of HAV
      and NoV on inert and lettuce surfaces. The MNV-1 appeared as the best candidate
      to simulate adhesion phenomena of all human pathogenic enteric viruses on all
      studied surfaces, while MS2 and GA bacteriophages could be a good alternative as
      model of viral adhesion on inert and lettuce surfaces. These results will be
      usable to design relevant experimental systems integrating adhesion behaviour of
      enteric viruses in the assessment of the efficiency of a technological or
      hygienic industrial process.

PMID- 22850374
TI  - Effectiveness of chitosan on the inactivation of enteric viral surrogates.
AB  - Chitosan is known to have bactericidal and antifungal activity. Although human
      noroviruses are the leading cause of non-bacterial gastroenteritis, information
      on the efficacy of chitosan against foodborne viruses is very limited. The
      objective of this work was to determine the effectiveness of different molecular
      weight chitosans against the cultivable human norovirus and enteric virus
      surrogates, feline calicivirus, FCV-F9, murine norovirus, MNV-1, and
      bacteriophages, MS2 and phiX174. Five purified chitosans (53, 222, 307, 421,
      ~1150 kDa) were dissolved in water, 1% acetic acid, or aqueous HCl pH = 4.3,
      sterilized by membrane filtration, and mixed with equal volume of virus to obtain
      a final concentration of 0.7% chitosan and 5 log(10) PFU/ml virus. Virus-chitosan
      suspensions were incubated for 3 h at 37  degrees C. Untreated viruses in PBS, in
      PBS with acetic acid, and in PBS with HCl were tested as controls. Each
      experiment was run in duplicate and replicated at least twice. Water-soluble
      chitosan (53 kDa) reduced phiX174, MS2, FCV-F9 and MNV-1 titers by 0.59, 2.44,
      3.36, and 0.34 log(10) PFU/ml respectively. Chitosans in acetic acid decreased
      phiX174 by 1.19-1.29, MS2 by 1.88-5.37, FCV-F9 by 2.27-2.94, and MNV-1 by 0.09
      0.28 log(10) PFU/ml, respectively. Increasing the MW of chitosan corresponded
      with an increasing antiviral effect on MS2, but did not appear to play a role for
      the other three tested viral surrogates. Overall, chitosan treatments showed the
      greatest reduction for FCV-F9, and MS2 followed by phiX174, and with no
      significant effect on MNV-1.

PMID- 22850375
TI  - Physiological adaptation of Escherichia coli after transfer onto refrigerated
      ground meat and other solid matrices: a molecular approach.
AB  - Bacteria on meat are subjected to specific living conditions that differ
      drastically from typical laboratory procedures in synthetic media. This study was
      undertaken to determine the behavior of bacteria when transferred from a rich
      liquid medium to solid matrices, as is the case during microbial process
      validation. Escherichia coli cultured in Brain-Heart Infusion (BHI) broth to
      different growth phases were inoculated in ground beef (GB) and stored at 5
      degrees C for 12 days or spread onto BHI agar and cooked meat medium (CMM), and
      incubated at 37 degrees C for several hours. We monitored cell densities and the
      expression of sigma factors and genes under their control over time. The initial
      growth phase of the inoculum influenced growth resumption after transfer onto BHI
      agar and CMM. Whatever the solid matrix, bacteria adapted to their new
      environment and did not perceive stress immediately after inoculation. During
      this period, the sigma(E) and sigma(H) regulons were not activated and rpoD mRNA
      levels adjusted quickly. The rpoS and gadA mRNA levels did not increase after
      inoculation on solid surfaces and displayed normal growth-dependent
      modifications. After transfer onto GB, dnaK and groEL gene expression was
      affected more by the low temperature than by the composition of a meat
      environment.

PMID- 22850376
TI  - Identification of lactic acid bacteria isolated during traditional fura
      processing in Ghana.
AB  - Fura is a millet-based spontaneously fermented dumpling produced and consumed in
      parts of West Africa, particularly Nigeria, Burkina Faso and Ghana. From eight
      traditional fura production sites in northern Ghana, 862 lactic acid bacteria
      were isolated and identified to species level using a combination of genotypic
      and phenotypic methods including (GTG)(5)-based PCR fingerprinting and 16S rRNA
      gene sequencing, multiplex PCR by means of recA gene sequence comparison,
      conventional morphological characteristics and carbohydrate fermentation
      profiling. During millet dough fermentation, pH decreased from 5.6-6.4 to 4.1-3.7
      and total lactic acid bacteria (LAB) counts increased from 4.4-5.3 to 7.9-9.2
      log(10) (cfu/g). The initial stages of the fermentation were characterized by co
      dominance of homo- and heterofermentative species of Pediococcus acidilactici,
      Weisella confusa, Lactobacillus fermentum, Lactobacillus reuteri, Lactobacillus
      salivarius, and Lactobacillus paraplantarum whereas L. fermentum was dominating
      at the end of the fermentation. L. fermentum was predominant in all fermentations
      (p < 0.05) and a high uniformity was observed among production sites regarding
      the dominance of L. fermentum. L. fermentum and W. confusa were isolated in all
      production sites and almost at all fermentation stages indicating that they are
      indigenous to traditional fura processing. The other LAB bacteria species which
      comprised a minor proportion of the total LAB occurred occasionally and in an
      irregular pattern among the production sites.

PMID- 22850377
TI  - Sporulation boundaries and spore formation kinetics of Bacillus spp. as a
      function of temperature, pH and a(w).
AB  - Sporulation niches in the food chain are considered as a source of hazard and are
      not clearly identified. Determining the sporulation environmental boundaries
      could contribute to identify potential sporulation niches. Spore formation was
      determined in a Sporulation Mineral Buffer. The effect of incubation temperature,
      pH and water activity on time to one spore per mL, maximum sporulation rate and
      final spore concentration was investigated for a Bacillus weihenstephanensis and
      a Bacillus licheniformis strain. Sporulation boundaries of B. weihenstephanensis
      and of B. licheniformis were similar to, or included within, the range of
      temperatures, pH and water activities supporting growth. For instance,
      sporulation boundaries of B. weihenstephanensis were evaluated at 5 degrees C, 35
      degrees C, pH 5.2 and a(w) 0.960 while growth boundaries were observed at 5
      degrees C, 37 degrees C, pH 4.9 and a(w) 0.950. Optimum spore formation was
      determined at 30 degrees C pH 7.2 for B. weihenstephanensis and at 45 degrees C
      pH 7.2 for B. licheniformis. Lower temperatures and pH delayed the sporulation
      process. For instance, the time to one spore per mL was tenfold longer when
      sporulation occurred at 10 degrees C and 20 degrees C, for each strain
      respectively, than at optimum sporulation temperature. The relative effect of
      temperature and pH on sporulation rates and on growth rates is similar. This work
      suggests that the influence of environmental factors on the quantitative changes
      in sporulation boundaries and rates was similar to their influence on changes in
      growth rate.

PMID- 22850378
TI  - Diversity of bacterial population of table olives assessed by PCR-DGGE analysis.
AB  - Nocellara Etnea and Geracese table olives are produced according to traditional
      process, in which lactic acid bacteria (LAB) and yeasts are the dominant
      microorganisms. With the aim to evaluate the effect of selected starter cultures
      on dynamics of bacterial population during fermentation and on growth/survival of
      Listeria spp. artificially inoculated into the olive brine, a polyphasic approach
      based on the combination of culturing and PCR-DGGE analysis was applied. Plating
      results showed a different concentration of the major bacterial groups considered
      among cultivars and the beneficial effect of LAB starters, which clearly
      inhibited Enterobacteriaceae. Moreover, results indicated that the brine
      conditions applied did not support the growth/survival of Listeria monocytogenes
      strain, artificially inoculated, highlighting the importance of selecting right
      fermentation parameters for assuring microbiological safety of the final
      products. Comparison of DGGE profile of Nocellara Etnea and Geracese table
      olives, displayed a great difference among cultivars, revealing a wide
      biodiversity within Lactobacillus population during Geracese olives fermentation.
      Based on cloning and sequencing of the most dominant amplicons, the presence,
      among others, of Lactobacillus paracollinoides and Lactobacillus coryniformis in
      Geracese table olives was revealed in table olives for the first time.

PMID- 22850379
TI  - Mycobiota and mycotoxin contamination of maize flours and popcorn kernels for
      human consumption commercialized in Spain.
AB  - Mycobiota and co-occurrence of aflatoxins, citrinin, ochratoxin A and zearalenone
      in 30 samples of maize flours and 30 of popcorn kernels purchased in Spain for
      human consumption were determined. The mycotoxin-producing ability of
      Aspergillus, Fusarium and Penicillium spp. was also studied. Total fungal counts
      of maize flours ranged from <10 to 8.4 * 10(4) CFU/g and predominant mycobiota
      belonged to Aspergillus spp. and Penicillium spp. In popcorn kernels samples the
      most frequent species were Aspergillus spp., Mucorales, Fusarium spp. and
      Penicillium spp. Aflatoxins were produced by Aspergillus flavus and Aspergillus
      parasiticus, citrinin by Penicillium citrinum and Penicillium verrucosum,
      ochratoxin A by Aspergillus niger and patulin by Aspergillus clavatus and
      Penicillium griseofulvum. Identification of all the mycotoxin-producing strains
      as well as some Aspergillus spp. difficult to identify using phenotypic
      characters only was also performed by molecular methods. Aflatoxins were detected
      in 14 maize flours and 2 popcorn kernels samples, while ochratoxin A was detected
      in 4 maize flours and 10 popcorn samples. Co-occurrence of aflatoxins and
      ochratoxin A was found in the 4 ochratoxin-positive maize flour samples. Citrinin
      and zearalenone were not detected. This is the first report of aflatoxins and
      ochratoxin A contamination in maize flours and popcorn kernels commercialized in
      Spain.

PMID- 22850380
TI  - Does proximity to neighbours affect germination of spores of non-proteolytic
      Clostridium botulinum?
AB  - It is recognised that inoculum size affects the rate and extent of bacterial
      spore germination. It has been proposed that this is due to spores interacting:
      molecules released from germinated spores trigger germination of dormant
      neighbours. This study investigated whether changes to the total number of spores
      in a system or proximity to other spores (local spore density) had a more
      significant effect on interaction between spores of non-proteolytic Clostridium
      botulinum strain Eklund 17B attached to defined areas of microscope slides. Both
      the number of spores attached to the slides and local spore density (number of
      spores per mm(2)) were varied by a factor of nine. Germination was observed
      microscopically at 15  degrees C for 8 h and the probability of, and time to,
      germination calculated from image analysis measurements. Statistical analysis
      revealed that the effect of total spore number on the probability of germination
      within 8 h was more significant than that of proximity to neighbours (local spore
      density); its influence on germination probability was approximately four-times
      greater. Total spore number had an even more significant affect on time to
      germination; it had a nine-fold greater influence than proximity to neighbours.
      The applied models provide a means to characterise, quantitatively, the effect of
      the total spore number on spore germination relative to the effect of proximity
      to neighbouring spores.

PMID- 22850381
TI  - Phenotypic and genetic characterization of antimicrobial resistance in Salmonella
      serovars isolated from retail meats in Alberta, Canada.
AB  - This study determined the prevalence of Salmonella serovars, antimicrobial
      resistance (AMR) and resistance genes in Salmonella isolated from retail meats
      purchased in Alberta, Canada. Samples were collected during one year period (May
      2007-April 2008) on weekly basis from 19 census divisions in Alberta. A total of
      564 samples including chicken (n = 206), turkey (n = 91), beef (n = 134) and pork
      (n = 133) were purchased. Salmonella were recovered from chicken (40%), turkey
      (27%) and pork (2%) samples and was not found in ground beef. A total of 21, 8,
      and 3 different serovars were recovered from chicken, turkey and pork meats,
      respectively. Salmonella Hadar was most common in chicken whereas S. Heidelberg
      was common in turkey meat. Overall 29% (32/110) of isolates were susceptible to
      tested antimicrobials and resistance to ciprofloxacin, amikacin and nalidixic
      acid was not found in any isolate. Multiresistance (>=2 antimicrobials) was found
      in 56% of isolates. Resistance to amoxicillin-clavulanic acid (AMC), ceftiofur
      (TIO), and ceftriaxone (CRO) was found in about 21% of chicken and 25% of turkey
      isolates. Resistance to either of tetracycline (TET), streptomycin (STR) or
      ampicillin (AMP) was unconditionally associated with S. Hadar but resistance to
      either of TET, AMP, AMC, TIO, CRO or cefoxitin was associated with S. Heidelberg.
      The strA/B (42% isolates), tet(A) (28% isolates), bla(CMY-2) (21% isolates) and
      bla(TEM) (17% isolates) were the most common resistance genes found. The bla(CMY
      2) and bla(TEM) genes were unconditionally associated with S. Heidelberg; tet(A)
      and strA/B with S. Hadar and tet(B) gene with S. Kentucky. The strA/B genes were
      not associated with S. Heidelberg. Our data suggests that the prevalence of
      Salmonella serovars varied by the meat type and that AMR and resistance genes
      varied by the Salmonella serovars.

PMID- 22850382
TI  - The prevalence, antimicrobial resistance and PFGE profiles of Laribacter
      hongkongensis in retail freshwater fish and edible frogs of southern China.
AB  - Laribacter hongkongensis is a novel emerging pathogen associated with human
      gastroenteritis. We aimed to investigate the prevalence, antimicrobial resistance
      and genotypic relationship of 199 L. hongkongensis isolates from 690 intestinal
      samples of fish and frogs. These samples were collected from retail markets in
      the city of Guangzhou in southern China from October 2008 to September 2009. L.
      hongkongensis was detected in from 80 (16.3%) out of 490 freshwater fish, and
      this number included 76 (32.3%) out of 235 grass carp and 4 (14.8%) out of 27
      bighead carp. A higher isolation rate of 59.5% (119 out of 200) was observed in
      edible frogs. The isolation rate was highest in the spring in comparison with
      other seasons. Notably, 63.8% of the isolates were resistant to at least one
      class of antimicrobial agents. Analysis by pulsed-field gel electrophoresis
      (PFGE) revealed that the isolates could be grouped into three clusters. Isolates
      from fish intestines were grouped into two clusters: cluster I and II. Isolates
      of frog-origin and several fish-origin isolates were grouped into cluster III.
      Two patient-derived strains could be classed into cluster III. Extensive genetic
      heterogeneity among the isolates was observed. The results indicate that L.
      hongkongensis isolates exhibits host tropism, extensive resistance to widely used
      antimicrobials and diverse biological evolution in an aquatic environment. The
      frog is more likely than the freshwater fish to be the potential source for human
      infection with L. hongkongensis.

PMID- 22850383
TI  - Tracing Campylobacter jejuni strains along the poultry meat production chain from
      farm to retail by pulsed-field gel electrophoresis, and the antimicrobial
      resistance of isolates.
AB  - In this study Campylobacter jejuni isolates were recovered from birds, carcasses
      and carcass portions from two broiler chicken flocks and from equipment used for
      carcass and meat processing along the production chain from farms to retail
      stores. Isolates were subjected to pulsed-field gel electrophoresis (PFGE) using
      SmaI and KpnI restriction enzymes and their antimicrobial susceptibilities were
      determined. C. jejuni was recovered from product and equipment used with both
      flocks at each point in the production chain. The prevalence of C. jejuni in
      poultry products at retail stores was 58.97% (flock 1) and 69.23% (flock 2). SmaI
      divided 122 C. jejuni strains from flock 1 and 106 from flock 2 into 17 and 13
      PFGE types, respectively. PFGE types H and F were present at all steps along the
      chain, from farms to retail products. Similarly, for both flocks PFGE type D was
      detected in crates, slaughterhouse and retail stores. Moreover, the PFGE types
      were highly diverse at the processing and retail steps. Most PFGE types were
      resistant to ciprofloxacin (95.45%) and tetracycline (81.82%); and multidrug
      resistant PFGE types were found in the final products. Our study showed that
      there were several points of cross-contamination of product along the chain, and
      a high diversity of PFGE types with antimicrobial resistance to ciprofloxacin and
      tetracycline in the retail products.

PMID- 22850384
TI  - Purification and characterization of a new bacteriocin active against
      Campylobacter produced by Lactobacillus salivarius SMXD51.
AB  - Strain SMXD51, isolated from chicken ceca and identified as Lactobacillus
      salivarius, produced a component that inhibits the growth of Gram-positive and
      Gram-negative bacteria and especially Campylobacter jejuni. The active peptide
      from the cell-free supernatant of Lb. salivarius SMXD51 was purified in three
      steps: (i) precipitation with 80% saturated ammonium sulfate, (ii) elution on a
      reversed phase SPE UPTI-CLEAN cartridge using different concentrations of
      acetonitrile, (iii) final purification by reversed phase HPLC on a C(18) column.
      The mode of action of this peptide of 5383.2 Da was identified as bactericidal,
      and its amino acid composition was established. This new bacteriocin SMXD51
      appears potentially very useful to reduce Campylobacter in poultry prior to
      processing.

PMID- 22850385
TI  - The first dairy product exclusively fermented by Propionibacterium
      freudenreichii: a new vector to study probiotic potentialities in vivo.
AB  - Dairy propionibacteria display probiotic properties which require high
      populations of live and metabolically active propionibacteria in the colon. In
      this context, the probiotic vector determines probiotic efficiency. Fermented
      dairy products protect propionibacteria against digestive stresses and generally
      contain a complex mixture of lactic and propionic acid bacteria. This does not
      allow the identification of dairy propionibacteria specific beneficial effects.
      The aim of this study was to develop a dairy product exclusively fermented by
      dairy propionibacteria. As they grow poorly in milk, we determined their
      nutritional requirements concerning carbon and nitrogen by supplementing milk
      ultrafiltrate (UF) with different concentrations of lactate and casein
      hydrolysate. Milk or UF supplemented with 50 mM lactate and 5 g L(-1) casein
      hydrolysate allowed growth of all dairy propionibacteria studied. In these new
      fermented dairy products, dairy propionibacteria remained viable and stress
      tolerant in vitro during minimum 15 days at 4  degrees C. The efficiency of milk
      fermented by the most tolerant Propionibacterium freudenreichii strain was
      evaluated in piglets. Viability and SCFA content in the colon evidenced survival
      and metabolic activity of P. freudenreichii. This work results in the design of a
      new food grade vector, which will allow preclinical and clinical trials.

PMID- 22850386
TI  - Effect of crust freezing applied alone and in combination with ultraviolet light
      on the survival of Campylobacter on raw chicken.
AB  - The application of crust freezing (CF) applied as a stand-alone treatment or in
      combination with ultraviolet (UV) light for reducing the level of artificially
      inoculated Campylobacter jejuni on raw chicken was investigated. CF air
      temperatures of -5, -15 and -27  degrees C (+/-3  degrees C) with freezing times
      of 70, 15 and 6 min, respectively, were used. The level of C. jejuni on chicken
      was also examined following subsequent refrigerated (0-4  degrees C) storage at 3
      and 7 days. All CF treatments resulted in significant reductions compared to
      untreated controls (P < 0.05). Although combining CF with UV also resulted in
      significant reductions for C. jejuni, the combined treatments were generally no
      more effective than treatment by CF alone. Overall, the color of chicken
      drumsticks was not affected by CF treatments (P >= 0.05). In general, CF resulted
      in increased drip loss (P < 0.05), which increased over storage time and was
      greater at higher CF temperatures. The current study indicates that CF has
      potential for reducing the levels of C. jejuni by between 0.5 and 1.5 log(10)
      CFU/g and impacts minimally on the color of treated skin.

PMID- 22850387
TI  - Phenotypic and transcriptomic analyses of Sigma L-dependent characteristics in
      Listeria monocytogenes EGD-e.
AB  - In this study the phenotypic and transcriptomic traits associated with the
      alternative sigma factor protein Sigma L in Listeria monocytogenes EGD-e were
      investigated. It was demonstrated that Sigma L is required for efficient growth
      in presence of stress associated with food preservative measures such as low
      temperature and organic acids. Furthermore, besides attenuation of swarming
      motility, the disruption of Sigma L in this bacterium also reduces resistance to
      a diverse range of toxic compounds, including some of the antibiotics used in
      listeriosis treatment. Genes under Sigma L-dependent transcriptional regulation
      were identified based on comparison of transcriptomes between exponentially
      growing cells of the EGD-e sigL null mutant and its parental strain cultivated
      under cold stress (3  degrees C) and optimized (37  degrees C) temperature
      conditions. Four hundred and forty genes under positive Sigma L-dependent
      transcriptional regulation were identified. The Sigma L regulon as revealed under
      these conditions comprises genes that code for proteins with diverse cellular
      functions including protein synthesis, nutrient transport, energy metabolism,
      cell envelope synthesis, and motility. The diverse range of transcriptome
      alterations induced by a sigL null mutation is thus consistent with the multiple
      phenotypic defects observed in the EGD-e DeltasigL mutant. These results
      demonstrate that Sigma L provides important global transcription regulatory
      functions in L. monocytogenes EGD-e. These promote execution of various cellular
      processes and stress adaptation responses thereby enabling this bacterium to
      overcome various food preservation measures as well as antibiotics and other
      toxic chemicals.

PMID- 22850388
TI  - ITS-based detection and quantification of Alternaria spp. in raw and processed
      vegetables by real-time quantitative PCR.
AB  - A TaqMan real-time polymerase chain reaction (PCR) method was developed for
      specific detection of Alternaria spp. in foodstuffs. The method uses Alternaria
      specific primers and probe targeting the internal transcribed spacer regions ITS1
      and ITS2 of the rRNA gene, and a positive amplification control based on 18S rRNA
      gene. The applicability of the real-time PCR protocol was assessed through
      analysis of 190 commercial food samples, including 80 fresh fruit and vegetable
      samples and 110 processed foodstuffs. The assay demonstrated the presence of
      Alternaria spp. DNA in 46 out of the 80 raw samples (57.5%) and in 66 out of the
      110 processed samples (60%), enabling quantitative detection of Alternaria spp.
      DNA at levels as low as 1 CFU/g. The estimated Alternaria counts obtained by real
      time PCR showed a good relationship (R(2) = 0.9006, P < 0.01) with the Alternaria
      counts obtained by plating on Potato Carrot Agar (PCA). The developed real-time
      PCR assay provides a useful tool for early detection of Alternaria spp. and could
      be applied as a quality and biosecurity marker of raw materials and final
      products in the fruits and vegetables processing industries.

PMID- 22850389
TI  - An integrative approach to identify Bacillus weihenstephanensis resistance
      biomarkers using gene expression quantification throughout acid inactivation.
AB  - The aim of this study was to define an integrative approach to identify
      resistance biomarkers using gene expression quantification and mathematical
      modelling. Mid-exponentially growing cells were transferred into acid conditions
      (BHI, pH 4.6) to obtain inactivation kinetics, performed in triplicate. The
      inactivation curve was fitted with a mixed Weibull model. This model allowed to
      differentiate two subpopulations with various acid resistances among the initial
      population. In parallel, differential gene expression was quantified by RT-qPCR.
      While narL was down-regulated throughout acid inactivation, sigB and katA were up
      regulated. sigB expression up-regulation peak was correlated to the less
      resistant subpopulation when katA up-regulation, was correlated to the more
      resistant subpopulation. Moreover, differences in population structure were
      highlighted between each replicate. The higher proportion of the more resistant
      subpopulation was linked to a higher katA gene expression. These results suggest
      that sigB and katA might be used as different types of biomarkers, for instance
      to track moderate and high acid-resistance, respectively. The use of this
      approach combining RT-qPCR and predictive modelling to track cellular biomarker
      variations appears as an interesting tool to take into account physiological cell
      responses into mathematical modelling, allowing an accurate prediction of
      microbial behaviour.

PMID- 22850390
TI  - Inactivation of Vibrio parahaemolyticus and Vibrio vulnificus in oysters by high
      hydrostatic pressure and mild heat.
AB  - Several recent outbreaks associated with oysters have heightened safety concerns
      of raw shellfish consumptions, with the majority being attributed to Vibrio spp.
      The objective of this study was to determine the effect of high-hydrostatic
      pressure (HHP) followed by mild heating on the inactivation of Vibrio
      parahaemolyticus and Vibrio vulnificus in live oysters. Inoculated oysters were
      randomly subjected to: a) pressurization at 200-300 MPa for 2 min at 21  degrees
      C, b) mild heat treatment at 40, 45 or 50  degrees C for up to 20 min and c)
      pressure treatment of 200-300 MPa for 2 min at 21  degrees C followed by heat
      treatment at 40-50  degrees C. Counts of V. parahaemolyticus and V. vulnificus
      were then determined using the most probable number (MPN) method. Pressurization
      at 200-300 MPa for 2 min resulted in various degrees of inactivation, from 1.2 to
      >7 log MPN/g reductions. Heat treatment at 40 and 45  degrees C for 20 min only
      reduced V. parahaemolyticus and V. vulnificus by 0.7-2.5 log MPN/g while at 50 
      degrees C for 15 min achieved >7 log MPN/g reduction. HHP and mild heat had
      synergistic effects. Combinations such as HHP at 250 MPa for 2 min followed by
      heat treatment at 45  degrees C for 15 min and HHP at 200 MPa for 2 min followed
      by heat treatment at 50  degrees C for 5 min reduced both V. parahaemolyticus and
      V. vulnificus to non-detectable levels by the MPN method (<3 MPN/g). HHP at >=275
      MPa for 2 min followed by heat treatment at 45  degrees C for 20 min and HHP at
      >=200 MPa for 2 min followed by heat treatment at 50  degrees C for 15 min
      completely eliminated both pathogens in oysters (negative enrichment results).
      This study demonstrated the efficiency of HHP followed by mild heat treatments on
      inactivation of V. parahaemolyticus and V. vulnificus and could help the industry
      to establish parameters for processing oysters.

PMID- 22850391
TI  - The efficacy of nisin can drastically vary when produced in situ in model
      cheeses.
AB  - Nisin, a bacteriocin produced by strains of Lactococcus lactis, has a broad
      inhibitory effect against Gram-positive bacteria. This study investigated the
      efficacy of nisin Z against Lactobacillus sakei when produced by a nisin
      producing strain L. lactis in model cheeses manufactured with ultrafiltrated
      milk. These cheeses, containing 0, 4 or 10% of gelatin in their dry matter, were
      inoculated with both strains. Measurement of Lb. sakei loss of viability was an
      indirect indicator of nisin in situ efficacy. After 24 h, the loss of viability
      of Lb. sakei was from 0.73 +/- 0.14 to 3.30 +/- 0.60 log(10) cfu g(-1) in the
      cheeses with 0 and 10% of gelatin, respectively, indicating a better in situ
      efficacy of nisin when gelatin was incorporated. However, the concentration of
      nisin produced by Lactococcus was similar (3.5 MUg g(-1)) in all model cheeses
      when measured using an enzyme-linked immune sorbent assay (ELISA). The growth of
      Lactococcus was slightly improved when gelatin was incorporated, leading to a
      higher lactate concentration, which is one of the factors explaining the
      increased nisin efficacy. These results reinforced previous observations that
      prediction of nisin efficacy in complex food systems remains difficult.

PMID- 22850392
TI  - Inactivation of Escherichia coli O157:H7, Salmonella typhimurium and Listeria
      monocytogenes in apple juice with gaseous ozone.
AB  - This research was initiated to assess the efficacy of gaseous ozone for
      inactivation Escherichia coli O157:H7, Salmonella typhimurium and Listeria
      monocytogenes in apple juice. Juice samples with solids content of 18, 36, and 72
      degrees Brix inoculated with a culture cocktail of three foodborne pathogens
      were treated with gaseous ozone at a flow rate of 3.0 L/min and an ozone
      generation rate of 0.10, 0.90, 3.51, and 5.57 g/h for 0.5, 1, 5, and 10 min,
      respectively. The inactivation kinetics of gaseous ozone on foodborne pathogens
      conformed to the Weibull model. The time required to achieve a 5 log reduction
      (t(5d)) was estimated using the parameters of the Weibull model. The t(5d)
      increased with increasing solids content of apple juice. The ozone generation
      rate did not impart a significant effect (p > 0.05) on t(5d). Gaseous ozone is
      effective at inactivating foodborne pathogens in apple juice but the efficacy is
      dependent on the solids content of the juice sample.

PMID- 22850393
TI  - A novel method for high-throughput data collection in predictive microbiology:
      optical density monitoring of colony growth as a function of time.
AB  - Recently, the focus of predictive food microbiology has shifted towards more
      mechanistically-inspired modelling. Together with this trend, the need for
      methods that allow rapid data collection at the (intra)cellular level, as well as
      the intermediate subpopulation/colony level, has emerged. Although several
      experimental techniques are currently available to study colony dynamics in/on
      solid media, their widespread implementation as high-throughput methods remains a
      challenge. In this research, a novel method is presented to study colony growth
      based on optical density measurements performed in microtiter plates. An area
      scan procedure was applied to monitor individual Escherichia coli colonies in 48
      well plates at 30  degrees C. Based on a fixed threshold value to separate the
      object (colony) from the background, the colony area was determined as a function
      of time. With this technique, expansion of the colony in radial direction could
      be monitored. Practical limitations (i.e., maximum achievable resolution and
      colony size) of the proposed method were investigated. A comparison was made with
      existing methods at the level of hardware requirements, data acquisition and data
      processing. Overall, the novel optical density method proved to be a flexible,
      high-throughput tool for monitoring (the mechanisms of) microbial colony growth
      in solid(like) systems.

PMID- 22850394
TI  - Prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in
      food samples associated with foodborne illness in Alberta, Canada from 2007 to
      2010.
AB  - Consumption of foods containing Staphylococcus aureus can cause severe gastro
      intestinal illness. Given the fact that over the past decade, Canada has seen
      increasing rates of methicillin-resistant S. aureus (MRSA) carriage and
      infection, the objective of this study was to investigate the impact of
      methicillin-susceptible S. aureus (MSSA) and MRSA on foodborne illness in
      Alberta, Canada. Between January 2007 and December 2010, there were 693 food
      samples associated with foodborne investigations submitted to the Alberta
      Provincial Laboratory for Public Health (ProvLab). These foods were screened for:
      Bacillus cereus, Clostridium perfringens, S. aureus, Aeromonas spp.,
      Campylobacter spp., Escherichia coli O157:H7, Salmonella, Shigella spp., and
      Yersinia spp. S. aureus was identified in 10.5% (73/693) of samples, and of
      these, 59% (43/73) were co-contaminated with at least one other organism on the
      screening panel. The S. aureus positive samples included 29 meat, 20 prepared
      foods containing meat, 11 prepared foods not containing meat, 10 dairy, and three
      produce. Methicillin-resistance was not detected in any isolates tested. These
      findings indicate that the presence of S. aureus in food associated with
      foodborne investigations is a cause for concern, and although MRSA was not found,
      the potential for outbreaks exists, and ongoing surveillance should be sustained.

PMID- 22850395
TI  - Bacterial spore inactivation at 45-65  degrees C using high pressure processing:
      study of Alicyclobacillus acidoterrestris in orange juice.
AB  - High pressure processing (HPP) is a new non-thermal technology commercially used
      to pasteurize fruit juices and extend shelf-life, while preserving delicate
      aromas/flavours and bioactive constituents. Given the spoilage incidents and
      economic losses due to Alicyclobacillus acidoterrestris in the fruit juice
      industry, the use of high pressure (200 MPa - 600 MPa) in combination with mild
      temperature (45  degrees C-65  degrees C) for 1-15 min, to inactivate these
      spores in orange juice were investigated. As expected, the higher the
      temperature, pressure and time, the larger was the A. acidoterrestris
      inactivation. The survival curves were described by the first order Bigelow
      model. For 200 MPa, D(45  degrees C) = 43.9 min, D(55  degrees C) = 28.8 min,
      D(65  degrees C) = 5.0 min and z-value = 21.3  degrees C. At 600 MPa, D(45 
      degrees C) = 12.9 min, D(55  degrees C) = 7.0 min, D(65  degrees C) = 3.4 min and
      z-value = 34.4  degrees C. Spores were inactivated at 45  degrees C and 600 MPa,
      and at 65  degrees C only 200 MPa was needed to achieve reduction in spore
      numbers. Results demonstrated that HPP allowed A. acidoterrestris spore
      inactivation at lower temperatures (45-65  degrees C) than conventional thermal
      processing (85-95  degrees C) without pressure, yielding a fresher and higher
      quality preserved food.

PMID- 22850396
TI  - The effects of thyme (Thymus vulgaris) and rosemary (Rosmarinus officinalis)
      essential oils on Brochothrix thermosphacta and on the shelf life of beef
      packaged in high-oxygen modified atmosphere.
AB  - The objective of the study was to determine the Minimal Inhibitory Concentration
      (MIC) of thyme (29.4% thymol, 21.6% p-cymene) and rosemary essential oils (27.6%
      1,8-cineole, 13.5% limonene, 13.0% beta-pinene) against Brochothrix thermosphacta
      and to establish the feasibility of their use as components of modified
      atmosphere during beef refrigerated storage. The minimum inhibitory concentration
      (MIC) of thyme oil against B. thermosphacta is 0.05% and that of rosemary oil
      0.5%. The MIC values are independent on strain and temperature of growth, however
      the bactericidal effects are strain dependent. The addition of any of oil at a
      concentration equal to 2MIC to the modified atmosphere (80% O(2)/20% CO(2)) does
      not significantly influence the microbial quality of meat. At the same time, such
      a concentration of the essential oils was considerably detrimental to the
      organoleptic factors.

PMID- 22850397
TI  - Toxin profile, antibiotic resistance, and phenotypic and molecular
      characterization of Bacillus cereus in Sunsik.
AB  - Sunsik, a ready-to-eat food in Korea, is comprised of various agricultural and
      marine products, and has been an important concern in Bacillus cereus food
      poisoning. The aim of this study was to investigate the toxin profiles, genotypic
      and phenotypic patterns as well as antibiotic resistance of B. cereus strains
      isolated from Sunsik. A subtyping method known as automated repetitive sequence
      based PCR system (DiversiLabTM) was used to assess the intraspecific biodiversity
      of these isolates. Thirty-five B. cereus strains were isolated from 100
      commercial Sunsik samples, all of which harbored at least 1 enterotoxin gene. The
      detection rates of nheABC, hblCDA, cytK, and entFM enterotoxin gene among all
      isolates were 97%, 86%, 77%, and 100%, respectively. Most strains also produced
      corresponding enterotoxins such as HBL (83%) and NHE (94%). One strain (2.9%)
      carried the emetic toxin genes, including ces and EM1, and was positive for the
      HEp-2 cell emetic toxin assay. Most strains were positive for various biochemical
      tests such as salicin hydrolysis (86%), starch fermentation (89%), hemolysis
      (89%), motility test (100%) and lecithinase hydrolysis (89%). All isolates were
      susceptible to most antibiotics although they were highly resistant to beta
      lactam antibiotics. By using the automated rep-PCR system, all isolates were
      successfully differentiated, indicating the diversity of B. cereus strains
      present in Sunsik.

PMID- 22850398
TI  - Pickering emulsions prepared by layered niobate K4Nb6O17 intercalated with
      organic cations and photocatalytic dye decomposition in the emulsions.
AB  - We investigated emulsions stabilized with particles of layered hexaniobate, known
      as a semiconductor photocatalyst, and photocatalytic degradation of dyes in the
      emulsions. Hydrophobicity of the niobate particles was adjusted with the
      intercalation of alkylammonium ions into the interlayer spaces to enable
      emulsification in a toluene-water system. After the modification of interlayer
      space with hexylammonium ions, the niobate stabilized water-in-oil (w/o)
      emulsions in a broad composition range. Optical microscopy showed that the
      niobate particles covered the surfaces of emulsion droplets and played a role of
      emulsifying agents. The niobate particles also enabled the generation of oil-in
      water (o/w) emulsions in a limited composition range. Modification with
      dodecylammonium ions, which turned the niobate particles more hydrophobic, only
      gave w/o emulsions, and the particles were located not only at the toluene-water
      interface but also inside the toluene continuous phase. On the other hand,
      interlayer modification with butylammonium ions led to the formation of o/w
      emulsions. When porphyrin dyes were added to the system, the cationic dye was
      adsorbed on niobate particles at the emulsion droplets whereas the lipophilic dye
      was dissolved in toluene. Upon UV irradiation, both of the dyes were degraded
      photocatalytically. When the cationic and lipophilic porphyrin molecules were
      simultaneously added to the emulsions, both of the dyes were photodecomposed
      nonselectively.

PMID- 22850399
TI  - Characterization of labile organic carbon in coastal wetland soils of the
      Mississippi River deltaic plain: relationships to carbon functionalities.
AB  - Adequate characterization of labile organic carbon (LOC) is essential to the
      understanding of C cycling in soil. There has been very little evaluation about
      the nature of LOC characterizations in coastal wetlands, where soils are
      constantly influenced by different redox fluctuations and salt water intrusions.
      In this study, we characterized and compared LOC fractions in coastal wetland
      soils of the Mississippi River deltaic plain using four different methods
      including 1) aerobically mineralizable C (AMC), 2) cold water extractable C
      (CWEC), 3) hot water extractable C (HWEC), and 4) salt extractable C (SEC), as
      well as acid hydrolysable C (AHC) which includes both labile and slowly
      degradable organic C. Molecular organic C functional groups of these wetland
      soils were characterized by (13)C solid-state nuclear magnetic resonance (NMR).
      The LOC and AHC increased with soil organic C (SOC) regardless of wetland soil
      type. The LOC estimates by four different methods were positively and
      significantly linearly related to each other (R(2)=0.62-0.84) and with AHC
      (R(2)=0.47-0.71). The various LOC fractions accounted for <=4.3% of SOC whereas
      AHC fraction represented 16-49% of SOC. AMC was influenced positively by O/N
      alkyl and carboxyl C but negatively by alkyl C, whereas CWEC and SEC fractions
      were influenced only positively by carboxyl C but negatively by alkyl C in SOC.
      On the other hand, HWEC fraction was found to be only influenced positively by
      carbonyl C, and AHC positively by O/N-alkyl and alkyl C but negatively by
      aromatic C groups in SOC. Overall these relations suggested different
      contributions of various molecular organic C moieties to LOC in these wetlands
      from those often found for upland soils. The presence of more than 50% non-acid
      hydrolysable C suggested the dominance of relatively stable SOC pool that would
      be sequestered in these Mississippi River deltaic plain coastal wetland soils.
      The results have important implications to the understanding of the liability and
      refractory character of SOC in these wetlands as recent studies suggest marsh SOC
      to be an important C source in fueling hypoxia in the northern Gulf of Mexico.

PMID- 22850400
TI  - Characterization of organic, metal and trace element PM2.5 species and derivation
      of freeway-based emission rates in Los Angeles, CA.
AB  - On-road particulate matter (PM) was collected during a sampling campaign in March
      April of 2011 on two major Los Angeles freeways, I-710 and Route 110. I-710 is a
      major route for heavy-duty vehicles (HDVs) traveling to and from the Ports of
      Long Beach and Los Angeles, while Route 110 has a much lower HDV fraction -3.9%
      versus 11.4%. Two sets of samples were collected for each roadway, each set
      representing approximately 50 degrees h of on-road sampling. Concurrent sampling
      at a fixed site at the University of Southern California's (USC) downtown Los
      Angeles campus provided estimates of urban background levels. Chemical analysis
      was performed for elemental carbon (EC), organic carbon (OC), polycyclic aromatic
      hydrocarbons (PAHs), hopanes and steranes, and metals and trace elements. Freeway
      based emission rates (ERs) - mass per kilometer of freeway per hour - were
      calculated using mass concentrations, fuel characteristics, and traffic flow
      rates. These ERs are presented such that freeways could be treated as a line
      source of emissions for use in predictive models of population exposure for
      nearby communities. This data could also be used to assess the exposure of
      commuters to traffic-related PM2.5 emissions. ERs are compared to data from a
      previous fixed-site roadside study of I-710 as well as to reconstructed values
      from a tunnel study. ERs were generally lower (or comparable) on the gasoline
      vehicle dominated freeway (Route 110) than the freeway with more diesel trucks (I
      710), with EC and pyrene being notably lower on Route 110, findings consistent
      with the Route 110's lower HDV fraction. We found EC emission rates decreased
      over time suggesting that efforts to reduce diesel emissions from HDVs at the
      Ports of Los Angeles and Long Beach have been successful. While ERs for most of
      the organic species were within the range of values reported by previous studies,
      the present study found much higher ERs for metals and trace elements. This
      suggests that the sampling methods employed in this campaign are more efficient
      at capturing particles from sources such as resuspended road dust and wear from
      tires and brakes, which are usually not included in traditional sampling
      methodologies for assessing vehicular emissions (e.g. dynamometer studies).

PMID- 22850401
TI  - An updated and conservative systematic review and meta-analysis of
      epidemiological evidence on psychotic experiences in children and adults: on the
      pathway from proneness to persistence to dimensional expression across mental
      disorders.
AB  - BACKGROUND: The psychosis-proneness-persistence-impairment model of psychotic
      disorder incorporates notions of both phenomenological and temporal continuity
      (persistence) of psychotic experiences (PE), but not structural continuity.
      Specific testable propositions of phenomenological continuity and persistence are
      identified. Method Propositions are tested by systematic reviews of the
      epidemiology of PE, persistence of PE and disorder outcomes, and meta-analyses
      (including Monte Carlo permutation sampling, MCPS) of reported rates and odds
      ratios (ORs). RESULTS: Estimates of the incidence and prevalence of PE obtained
      from 61 cohorts revealed a median annual incidence of 2.5% and a prevalence of
      7.2%. Meta-analysis of risk factors identified age, minority or migrant status,
      income, education, employment, marital status, alcohol use, cannabis use, stress,
      urbanicity and family history of mental illness as important predictors of PE.
      The mode of assessment accounted for significant variance in the observed rates.
      Across cohorts, the probability of persistence was very strongly related to the
      rate of PE at baseline. Of those who report PE, ~20% go on to experience
      persistent PE whereas for ~80%, PE remit over time. Of those with baseline PE,
      7.4% develop a psychotic disorder outcome. CONCLUSIONS: Compelling support is
      found for the phenomenological and temporal continuity between PE and psychotic
      disorder and for the fundamental proposition that this relationship is
      probabilistic. However, imprecision in epidemiological research design,
      measurement limitations and the epiphenomenological nature of PE invite further
      robust scrutiny of the continuity theory.

PMID- 22850402
TI  - Vasorelaxant effects of aqueous leaf extract of Tridax procumbens on aortic
      smooth muscle isolated from the rat.
AB  - Tridax procumbens is commonly used in traditional medicine in southern part of
      Nigeria for the treatment of hypertension. However, the mechanism of its
      antihypertensive properties remains unclear. Attempts were made to investigate
      the properties of direct actions of aqueous extract of the leaves of T.
      procumbens on mechanical responses of smooth muscles in aortic ring preparations
      isolated from the rat. Endothelium-intact aortic rings, isolated from the
      normotensive rats, had been pre-contracted with noradrenaline, and cumulative
      addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a
      concentration-dependent relaxation. Aqueous extract of T. procumbens also
      attenuated the contractile responses to KCl and shifted the concentration
      response curve to the right. The contractile responses to serotonin were also
      attenuated and the concentration-response curve was shifted to the right in the
      presence of the extract. The results of this study indicated that aqueous leaf
      extract of T. procumbens possesses vasodilatory effects on the aortic smooth
      muscles isolated from the rat. Based on these results, a possible mechanism
      involved in the relaxing actions of the extract on vascular smooth muscle was
      discussed. The results of this study may provide a scientific basis for the use
      of this extract to the treatment of hypertension in Nigerian traditional
      medicine.

PMID- 22850403
TI  - Local differences in electrogastrographic responses to the stress of the mirror
      drawing test (MDT) as determined by multichannel electrogastrography.
AB  - Electrogastrograms (EGGs) were recorded in human subjects (n=58) at 16 locations
      on the thoraco-abdominal surface before (at rest) and during the stress of the
      mirror drawing test (MDT) and after having a test meal. The power amplitude
      ratios and power content ratios of MDT to rest (MDT/rest) and postprandial state
      to rest (PPR/rest) were compared between gastric channels 5 and 8, and the
      infraumbilical channels 12, 13, 14, 15, and 16. Generally, the ratio of the 3-cpm
      group in channels 5 and 8 was lower than that of the infraumbilical channels 12
      16 during MDT. In contrast, the ratios were higher in the epigastric channels
      than in the infraumbilical channels after a test meal. Significant differences
      between the epigstric and infraumbilical channels were found in the comparisons
      of the power content ratios. The infraumbilical channels were facilitated and the
      epigastric channels inhibited during MDT. After eating a meal, in contrast, the
      postprandial epigastric 3-cpm EGGs were facilitated. The epigastric 3-cpm EGG
      activity reflects gastric myoelectric activity, while the infraumbilical 3-cpm
      activity reflects that of the colon. Therefore, it is suggested that the acute
      stress of the MDT generally inhibited the gastric EGG and facilitated the colonic
      EGG, indicating gastric inhibition and colonic facilitation. The topographic EGG
      maps of the power content ratios and the absolute power ratios visually confirmed
      these findings.

PMID- 22850404
TI  - Effect of sugammadex on bronchial smooth muscle function in rats.
AB  - Sugammadex can encapsulate the steroid-based neuromuscular blocker molecule and
      results in rapid reversal of neuromuscular blockade induced by rocuronium and
      vecuronium. However, several cases of bronchospasm after the administration of
      sugammadex have been reported. The current study was carried out to determine
      whether sugammadex directly affects smooth muscle function of the airways. The
      ring strips of left main bronchi were isolated from male Wistar rats and
      isometric forces were measured. In the isolated bronchial smooth muscle tissues,
      sugammadex (10-8-10-3 M) had no effect on baseline tension or the acetylcholine
      (ACh; 30 uM)-induced sustained contraction. Moreover, sugammadex did not affect
      bronchial smooth muscle responsiveness to ACh. These findings indicate that
      sugammadex itself does not affect contractile function in bronchial smooth muscle
      of the rat.

PMID- 22850405
TI  - Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood
      brain barriers by uptake1 and uptake2.
AB  - Uptake1 and uptake2 transporters are involved in the extracellular clearance of
      biogenic amine neurotransmitters at synaptic clefts. We looked for them at the
      blood-brain barrier (BBB) and blood-retina barriers (BRB), where they could be
      involved in regulating the neurotransmitter concentration and modulate/terminate
      receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1
      3/Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in
      the transport of xenobiotics. We used in situ carotid perfusion of prototypic
      substrates like [(3)H]-1-methyl-4-phenylpyridinium ([(3)H]-MPP(+)), [(3)H]
      histamine, [(3)H]-serotonin, and [(3)H]-dopamine, changes in ionic composition
      and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB
      and BRB. We showed that uptake1 and uptake2 are involved in the transport of
      [(3)H]-dopamine and [(3)H]-MPP(+) at the blood luminal BRB, but not at the BBB.
      These functional studies, together with quantitative RT-PCR and confocal imaging,
      suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4),
      uptake2, and Mate1 on both the luminal and abluminal sides. However, we found
      evidence for functional Net and Oct1 transporters at the luminal BRB. These
      heterogeneous transport properties of the brain and retina NVUs suggest that the
      BBB helps protect the brain against biogenic amine neurotransmitters in the
      plasma while the BRB has more of a metabolic/endocrine role.

PMID- 22850408
TI  - Understanding blood/material interactions: contributions from the Columbia
      University Biomaterials Seminar.
AB  - Meetings of the Columbia University Biomaterial Seminars held in the 1970s and
      80s are recounted from the personal perspectives of a participant and attendee.
      Important lessons regarding blood/foreign surface interactions that emanated from
      the seminars are reproduced along with a list of contemporary contributing
      members. These lessons continue to have broad relevance in furthering our
      understanding of the behavior of blood whenever it is used in artificial organ
      technology.

PMID- 22850406
TI  - Cerebral blood flow and metabolism of hyperperfusion after cerebral
      revascularization in patients with moyamoya disease.
AB  - In moyamoya disease (MMD), surgical revascularization may be complicated with
      postoperative hyperperfusion. We analyzed cerebral perfusion and metabolism using
      positron emission tomography (PET) or single-photon emission computed tomography
      (SPECT) before and after bypass surgery on 42 sides of 34 adult patients with
      MMD. In seven cases (16.7%) with symptomatic hyperperfusion, diagnosed by
      qualitative (123)I-iodoamphetamine (IMP) SPECT, a subsequent PET study during
      postoperative subacute stages revealed significantly increased cerebral blood
      flow (CBF) from 34.1 +/- 8.2 to 74.3 +/- 12.8 mL/100 g per minute (P<0.01), a
      persistent increase in cerebral blood volume (CBV) from 5.77 +/- 1.67 to 7.01 +/-
      1.44 mL/100 g and a significant decrease in oxygen extraction fraction (OEF) from
      0.61 +/- 0.09 to 0.40 +/- 0.08 (P<0.01). Mean absolute CBF values during
      symptomatic hyperperfusion were more than the normal control +2 standard
      deviations, the predefined criteria of PET. Interestingly, two patients with
      markedly increased cerebral metabolic rate of oxygen (CMRO(2)) at hyperperfusion
      were complicated with postoperative seizure. Among preoperative PET parameters,
      increased OEF was the only significant risk factor for symptomatic hyperperfusion
      (P<0.05). This study revealed that symptomatic hyperperfusion in MMD is
      characterized by temporary increases in CBF >100% over preoperative values caused
      by prolonged recovery of increased CBV.

PMID- 22850407
TI  - Blood-spinal cord barrier pericyte reductions contribute to increased capillary
      permeability.
AB  - The blood-spinal cord barrier (BSCB) regulates molecular exchange between blood
      and spinal cord. Pericytes are presumed to be important cellular constituents of
      the BSCB. However, the regional abundance and vascular functions of spinal cord
      pericytes have yet to be determined. Utilizing wild-type mice, we show that
      spinal cord pericyte capillary coverage and number compared with the brain
      regions are reduced most prominently in the anterior horn. Regional pericyte
      variations are highly correlated with: (1) increased capillary permeability to
      350 Da, 40,000 Da, and 150,000 Da, but not 2,000,000 Da fluorescent vascular
      tracers in cervical, thoracic, and lumbar regions and (2) diminished endothelial
      zonula occludens-1 (ZO-1) and occludin tight junction protein expression.
      Pericyte-deficient mutations (Pdgfrbeta(F7/F7) mice) resulted in additional
      pericyte reductions in spinal cord capillaries leading to overt BSCB disruption
      to serum proteins, accumulation in motor neurons of cyotoxic thrombin and fibrin
      and motor neuron loss. Barrier disruption in perciyte-deficient mice coincided
      with further reductions in ZO-1 and occludin. These data suggest that pericytes
      contribute to proper function of the BSCB at the capillary level. Regional
      reductions in spinal cord pericytes may provide a cellular basis for heightened
      spinal cord barrier capillary permeability and motor neuron loss.

PMID- 22850409
TI  - Size and phospholipid coating of lipid droplets in the diet of young mice modify
      body fat accumulation in adulthood.
AB  - BACKGROUND: In addition to contemporary lifestyle factors that contribute to the
      increased obesity prevalence worldwide, early nutrition is associated with
      sustained effects on later life obesity. We hypothesized that physical properties
      of dietary lipids contribute to this nutritional programming. We developed a
      concept infant formula (IMF) with large, phospholipid-coated lipid droplets
      (Nuturis; Danone Research, Paris, France) and investigated its programming effect
      on metabolic phenotype later in life. METHODS: Male C57Bl/6j mice were fed a
      control formula (Control IMF) or Nuturis (Concept IMF) diet between postnatal day
      (PN)16 and PN42. All mice were subsequently fed a Western-style diet (WSD) until
      PN126. Body composition was monitored repeatedly by dual-energy X-ray
      absorptiometry between PN42 and PN126. RESULTS: Concept IMF slightly increased
      lean body mass as compared with Control IMF at PN42 but did not affect fat mass.
      Upon 84 d of WSD feeding, the Concept IMF group showed reduced fat accumulation
      as compared with Control IMF. In addition, fasting plasma leptin, resistin,
      glucose, and lipids were significantly lower in the Concept IMF group.
      CONCLUSION: Large phospholipid-coated lipid droplets in young mice reduced fat
      accumulation and improved metabolic profile in adulthood. These data emphasize
      that physical properties of early dietary lipids contribute to metabolic
      programming.

PMID- 22850410
TI  - A clinicopathological analysis of 40 cases of ovarian Sertoli-Leydig cell tumors.
AB  - OBJECTIVE: To evaluate the clinicopathological features of ovarian Sertoli-Leydig
      cell tumors (SLCTs) and to explore the reasonable therapy. METHODS: A total of 40
      cases of SLCTs were retrospectively reviewed. RESULTS: The incidence of SLCTs was
      0.41%, with a median age of 28 years. All tumors were confined to one ovary. Four
      tumors were well differentiated, 14 were intermediately differentiated, 20 were
      poorly differentiated, and 2 were undefined; 2 cases had heterologous elements,
      and 3 had a retiform pattern. The patients were classified into 3 groups:
      androgen excess (25/40), estrogen excess (6/40), and no endocrine changes (9/40).
      The percentages of tumors >10 cm in diameter were 8.0%, 16.7% and 40.0%,
      respectively; the percentages of poor differentiation were 40.0%, 50.0% and
      77.8%, respectively; and the percentages of tumor rupture were 20.0%, 16.7% and
      66.7%, respectively. One patient underwent cystectomy, 27 underwent unilateral
      salpingo-oophorectomy, and 12 underwent total hysterectomy and bilateral salpingo
      oophorectomy. A total of 23 patients received postoperative chemotherapy. One
      patient died of diabetic nephropathy, and 3 were lost to follow up. The remaining
      36 were followed up from 12 to 377 (average 70.4) months. Two patients with stage
      Ic tumors of poor differentiation had a recurrence within 13 and 21 months, and
      both obtained complete remission after the second surgery and chemotherapy.
      CONCLUSIONS: The prognosis of SLCTs is good, although poorly differentiated
      tumors may recur. Conservative surgery is acceptable for young patients wishing
      to preserve fertility, and postoperative adjuvant chemotherapy and long-term
      follow up are recommended to those with high-risk factors.

PMID- 22850411
TI  - A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in
      early stage endometrioid endometrial cancer.
AB  - PURPOSE: To evaluate local control, survival and toxicity in patients with early
      stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose
      rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen.
      METHODS: We reviewed records of 414 patients with stage IA to stage II
      endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157
      patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal
      cylinder brachytherapy and constitute the study population. Dose was prescribed
      at the cylinder surface and delivered twice weekly in the post-operative setting.
      Local control and survival rates were calculated by the Kaplan-Meier method.
      RESULTS: All 157 patients completed the prescribed course of VB. Median follow-up
      time was 22.8 months (range, 1.5-76.5). Two patients developed vaginal
      recurrence, one in the periurethral region below the field and one in the fornix
      after treatment with a 2.5-cm cylinder. Three patients developed regional
      recurrence in the para-aortic region. Two patients developed distant metastasis
      (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%,
      locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year
      overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal,
      genitourinary or skin long-term toxicity was reported for any patient.
      CONCLUSION: Vaginal brachytherapy alone in early-stage endometrial cancer
      provides excellent results in terms of locoregional control and disease-free
      survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the
      cylinder surface was well-tolerated with minimal late toxicity.

PMID- 22850412
TI  - Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and
      intravaginal radiation for stage I-II papillary serous endometrial cancer.
AB  - OBJECTIVE: The purpose of this study is to report our single-institution
      experience with concurrent adjuvant intravaginal radiation (IVRT) and
      carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous
      carcinoma (UPSC). METHODS: From 10/2000 to 12/2009, 41 women with stage I-II UPSC
      underwent surgery followed by IVRT (median dose of 21 Gy in 3 fractions) and
      concurrent carboplatin (AUC=5-6) and paclitaxel (175 mg/m(2)) for six planned
      cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan-Meier method
      was used to estimate survival, and the log-rank test was used for comparisons.
      RESULTS: Median patient age was 67 years (51-80 years). Surgery included
      hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental
      biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in
      73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty
      five patients (85%) completed all planned treatment. With a median follow-up time
      of 58 months, the 5-year disease-free (DFS) and overall survival (OS) rates were
      85% (95%CI, 73-96%) and 90% (95%CI, 80-100%). The 5-year pelvic, para-aortic, and
      distant recurrence rates were 9%, 5%, and 10%, respectively. There were no
      vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were
      successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%;
      p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease.
      CONCLUSIONS: Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT
      provide excellent outcomes for early stage UPSC. Whether this regimen is superior
      to pelvic radiation will require confirmation from the ongoing randomized trial.

PMID- 22850413
TI  - How to improve cytoreductive surgery for advanced ovarian cancer and talk about
      it in a common language.

PMID- 22850414
TI  - In vitro amyloid aggregate forming ability of TGFBI mutants that cause corneal
      dystrophies.
AB  - PURPOSE: We investigated the in vitro amyloid aggregation ability of TGFBI
      (transforming growth factor beta-induced) mutants causing corneal dystrophies
      (CDs). METHODS: Peripheral blood samples were collected from 42 unrelated Chinese
      CD patients and 185 healthy subjects for mutation screening in all TGFBI coding
      exons and flanking introns. The expression vector pCMV6_TGFBI containing wild
      type, Arg-124, or Arg-555 mutations was transfected to HEK293 cells. Cell-free
      media was incubated with amyloid-beta (Abeta) (1-40) peptides with or without a
      chemical osmolyte, trimethylamine N-oxide (TMAO), for different time intervals.
      After ultracentrifugation, protein aggregates were analyzed by denatured gel
      electrophoresis. The effect of TMAO on chemical and morphological properties of
      Abeta aggregation was examined. RESULTS: TGFBI sequencing analysis showed
      c.Arg124Cys in all 6 lattice CD patients, c.Arg555Glu in all 11 granular CD type
      1 patients, and c.Arg124His in 22 of 25 granular CD type 2 patients. Double
      heterozygosity (c.307-308delCT and c.Arg124His) was detected in one GCD2 patient.
      After transfection, cell-free media containing Arg-124 TGFBIp led to Abeta
      aggregation within 12 hours, whereas wild-type and Arg-555 mutant displayed
      aggregation after 24 hours. Western blot and Congo red binding assays showed that
      TMAO dose-dependently suppressed Arg-124-induced Abeta aggregation. Transmission
      electron microscopy showed that TMAO reduced the fibrillar aggregates caused by
      Abeta and c.124R > H mutated TGFBIp. CONCLUSIONS: TGFBI sequence heterogeneity
      was observed in Chinese CD patients. TMAO reduced amyloid aggregation caused by
      Arg-124 mutants, which suggests a potential chemical-based treatment for CDs.

PMID- 22850416
TI  - Elastic properties of human lens zonules as a function of age in presbyopes.
AB  - PURPOSE: To investigate the elastic properties of human lens zonules as a
      function of age in presbyopes. METHODS: We studied 16 presbyopic human donor eyes
      (ages 47-97). Anterior eye sections with crystalline lens, zonules, ciliary body,
      and sclera were stretched radially. The stretching device consisted of a chamber
      filled with balanced salt solution and eight radial hooks to hold the anterior
      eye section. Radial stretching was created with a stepper motor connected to a
      digital outside micrometer for linear displacement and digital balance for force
      measurement. Three eye globes were used to test our methodology. For 13 eye
      globes, the spring constant, elastic modulus of the zonular system, and Young's
      modulus of the zonules were calculated. RESULTS: We found linear dependence for
      force-elongation and force-strain relationships at all ages. In young presbyopic
      eyes (ages 47-60), the Young's modulus of the zonules was 340 mN/mm(2), whereas
      in older eyes (ages 83-97) it was significantly lower at 270 mN/mm(2). However,
      the correlation coefficient between Young's modulus and age (47-97 years) was not
      significant with P = 0.063. CONCLUSIONS: The zonular system in presbyopic eyes
      was linear elastic, and the Young's modulus of the zonules decreased 20% from
      presbyopic age to late presbyopic age. However, there was no significant
      correlation between Young's modulus and age in presbyopes.

PMID- 22850415
TI  - Expression of angiogenesis-related factors in human corneas after cultivated oral
      mucosal epithelial transplantation.
AB  - PURPOSE: We analyzed the expression of angiogenesis-related factors in corneal
      tissues that had undergone previously autologous cultivated oral mucosal
      epithelial transplantation (COMET). METHODS: Six eyes from four chemically- and
      two thermally-injured patients with limbal stem cell deficiency who received
      COMET to promote wound healing were studied retrospectively. Immunoconfocal
      microscopy was performed on corneal specimens from the patients after COMET, as
      well on normal corneas, conjunctiva, and oral mucosa for keratin 8, fibroblast
      growth factor-2 (FGF-2), VEGF, collagen XVIII (endostatin), pigment epithelium
      derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), tissue
      inhibitor of metalloproteinase-3 (TIMP-3), thrombospondin-1 (TSP-1), and
      interleukin-1 receptor antagonist (IL-1ra). RESULTS: FGF-2, VEGF, endostatin,
      PEDF, and IL-1ra were detected in all the samples, with signals for FGF-2, VEGF,
      and IL-1ra localized to the full-thickness epithelial layer, as signals for
      endostatin limited to the basement membrane. Expression of PEDF varied in
      tissues, with a preferential expression in the suprabasal epithelial layer. FGF-2
      and IL-1ra were abundantly expressed in the basal epithelial layer in specimens
      with increased stratification. Signals for sFlt-1, TIMP-3, and TSP-1 were
      detected in normal corneal epithelium, and in a specimen containing corneal
      epithelium, but were negative in all other specimens. CONCLUSIONS: Expression of
      FGF-2, VEGF, PEDF, endostatin, and IL-1ra was similar in normal corneas,
      conjunctiva, oral mucosa, and corneas after COMET. Expression of sFlt-1, TIMP-3,
      and TSP-1 was limited to normal corneas and negative for other tissues. A lack of
      the aforementioned antiangiogenic factors may contribute to the peripheral
      corneal neovascularization seen after COMET.

PMID- 22850417
TI  - Individual differences in binocular coordination are uncovered by directly
      comparing monocular and binocular reading conditions.
AB  - PURPOSE: We evaluated systematically binocular coordination during a reading task
      by comparing binocular and monocular reading, and considering the potential
      effects of individual heterophoria and eye dominance. METHODS: A total of 13
      participants (aged 19-29 years, refractive errors -0.5 to 0.125 diopters [D])
      read single sentences in a haploscope while eye movements were measured with an
      EyeLinkII eyetracker. RESULTS: When reading monocularly, saccade amplitudes
      increased by 0.04 degrees and first fixation durations became longer by
      approximately 10 ms. Furthermore, saccade disconjugacies increased, and
      compensatory vergence drifts during fixation turned into a divergent drift
      relative to the viewing distance. The vergence angle adjusted for the actual
      viewing distance became less convergent during monocular reading by 0.5 degrees.
      Moreover, in participants who were almost orthophoric, only the first fixation
      duration became longer (by 20 ms) when the reading conditions changed from
      binocular to monocular. For exophoric participants, all parameters of binocular
      coordination changed, and first fixation duration decreased by 20 ms. When
      reading monocularly, no differences between the dominant right eye and the
      nondominant left eye were found. CONCLUSIONS: Because of obvious differences in
      binocular coordination between monocular and binocular reading, some vergence
      adjustments are driven actively by fusional processes. Furthermore, higher
      demands on these binocular fusional processes can be uncovered only by a detailed
      evaluation of monocular reading conditions.

PMID- 22850418
TI  - Survey of nutrition knowledge of physicians in Kuwait.
AB  - OBJECTIVE: The objective of the present study was to determine whether nutrition
      knowledge differs between male and female physicians working in Kuwait City,
      Kuwait. DESIGN: The study employed a cross-sectional analysis of physician's
      nutrition knowledge by using a sixteen-item multiple-choice questionnaire.
      SETTING: Governmental hospitals in Kuwait City, Kuwait. SUBJECTS: One hundred
      Kuwaiti physicians (fifty males; fifty females) working in Kuwait City, Kuwait.
      RESULTS: A response rate of 73% was achieved (forty males; thirty-three females).
      The mean percentage of correctly answered questions was 60 %. The male and female
      physicians averaged 56% and 65% of correct responses, respectively (P50?042).
      However, only for two questions did male and female physicians' scores differ
      significantly (P,0?05). The two age groups (,40 years; $40 years) had equal mean
      total correct scores (60 %, P50?935). Physicians' knowledge was greatest for
      topics that have received a great deal of media coverage in Kuwait. Most (70 %)
      of the physicians described their nutrition knowledge as 'moderate'. CONCLUSIONS:
      Physicians in Kuwait gave inaccurate information regarding common problems in
      Kuwaitis such as obesity, hypertension and osteoporosis. In view of the public's
      perception of the role of the physician in providing nutrition advice, it is
      imperative that nutrition and diet training be part of continuing medical
      education to bridge these deficiencies in physicians' knowledge.

PMID- 22850419
TI  - Neogenesis of lymphoid structures and antibody responses occur in human melanoma
      metastases.
AB  - Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid
      organs, is frequently observed in chronically inflamed tissues, during the course
      of autoimmune, infectious, and chronic graft rejection diseases, in which a
      sustained lymphocyte activation occurs in the presence of persistent antigenic
      stimuli. The presence of such ectopic lymphoid structures has also been reported
      in primary lung, breast, and germline cancers, but not yet in melanoma. In this
      study, we observed ectopic lymphoid structures, defined as lymphoid follicles
      comprising clusters of B lymphocytes and follicular dendritic cells (DC),
      associated with high endothelial venules (HEV) and clusters of T cells and mature
      DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles
      contained germinal centers. In contrast to metastatic lesions, primary melanomas
      did not host follicles, but many contained HEVs, suggesting an incomplete
      lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin
      genes in the B cells of microdissected follicles revealed clonal amplification,
      somatic mutation and isotype switching, indicating a local antigen-driven B-cell
      response. Surprisingly, IgA responses were observed despite the nonmucosal
      location of the follicles. Taken together, our findings show the existence of
      lymphoid neogenesis in melanoma and suggest that the presence of functional
      ectopic lymphoid structures in direct contact with the tumor makes the local
      development of antimelanoma B- and T-cell responses possible.

PMID- 22850420
TI  - Translation regulation as a therapeutic target in cancer.
AB  - Protein synthesis is a vital cellular process that regulates growth and
      metabolism. It is controlled via signaling networks in response to environmental
      changes, including the presence of nutrients, mitogens, or starvation. The
      phosphorylation state of proteins involved in translation initiation is a
      limiting factor that regulates the formation or activity of translational
      complexes. In cancer cells, hyperactivated signaling pathways influence
      translation, allowing uncontrolled growth and survival. In addition, several
      components of translation initiation have been found to be mutated,
      posttranslationally modified, or differentially expressed, and some act as
      oncogenes in cancer cells. Translational alterations can increase the overall
      rate of protein synthesis as well as activate regulatory mechanisms leading to
      the translation of specific messenger RNAs for proteins that promote cancer
      progression and survival. Many recent studies investigating such mechanisms have
      produced ideas for therapeutic intervention. This review describes altered
      mechanisms of protein synthesis in human cancers and discusses therapeutic
      approaches based on the targeting of translation.

PMID- 22850421
TI  - Reciprocal metabolic reprogramming through lactate shuttle coordinately
      influences tumor-stroma interplay.
AB  - Cancer-associated fibroblasts (CAF) engage in tumor progression by promoting the
      ability of cancer cells to undergo epithelial-mesenchymal transition (EMT), and
      also by enhancing stem cells traits and metastatic dissemination. Here we show
      that the reciprocal interplay between CAFs and prostate cancer cells goes beyond
      the engagement of EMT to include mutual metabolic reprogramming. Gene expression
      analysis of CAFs cultured ex vivo or human prostate fibroblasts obtained from
      benign prostate hyperplasia revealed that CAFs undergo Warburg metabolism and
      mitochondrial oxidative stress. This metabolic reprogramming toward a Warburg
      phenotype occurred as a result of contact with prostate cancer cells.
      Intercellular contact activated the stromal fibroblasts, triggering increased
      expression of glucose transporter GLUT1, lactate production, and extrusion of
      lactate by de novo expressed monocarboxylate transporter-4 (MCT4). Conversely,
      prostate cancer cells, upon contact with CAFs, were reprogrammed toward aerobic
      metabolism, with a decrease in GLUT1 expression and an increase in lactate upload
      via the lactate transporter MCT1. Metabolic reprogramming of both stromal and
      cancer cells was under strict control of the hypoxia-inducible factor 1 (HIF1),
      which drove redox- and SIRT3-dependent stabilization of HIF1 in normoxic
      conditions. Prostate cancer cells gradually became independent of glucose
      consumption, while developing a dependence on lactate upload to drive anabolic
      pathways and thereby cell growth. In agreement, pharmacologic inhibition of MCT1
      mediated lactate upload dramatically affected prostate cancer cell survival and
      tumor outgrowth. Hence, cancer cells allocate Warburg metabolism to their
      corrupted CAFs, exploiting their byproducts to grow in a low glucose environment,
      symbiotically adapting with stromal cells to glucose availability.

PMID- 22850423
TI  - The use of 'damage control orthopedics' techniques in children with segmental
      open femur fractures.
AB  - Femur fractures are common long bone injuries in children. Open femur fractures;
      however, are uncommon. Traditionally, long-term external fixation has been
      recommended for treatment of these fractures. Damage control orthopedics is a
      well-recognized concept in adult orthopedic trauma management. Little or no
      literature exists demonstrating the use of damage control orthopedics principles
      in children. These cases illustrate the utility of these techniques as a
      temporary bridge in the management of open, segmental pediatric femur fractures
      complicated by severe soft tissue injury and bone loss, which were managed
      definitively by submuscular bridge plates.

PMID- 22850422
TI  - Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS
      costimulation of Foxp3(+) T-regulatory cells.
AB  - Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death
      among women. Despite its immunogenicity, effective antitumor responses are
      limited, due, in part, to the presence of forkhead box protein 3-positive
      (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the
      mechanisms that regulate the accumulation and the suppressive function of these
      Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of
      Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to
      the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The
      expansion and the suppressive function of these cells were strictly dependent on
      ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC).
      Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity
      of tumor pDCs, and their number directly correlated with the numbers of pDCs in
      the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be
      strong predictors for disease progression in patients with ovarian cancer, with
      ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg
      cells. These findings suggest an essential role for pDCs and ICOS-L in
      immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor
      progression in ovarian cancer.

PMID- 22850425
TI  - Kinetic signatures of microRNA modes of action.
AB  - MicroRNAs (miRNAs) are key regulators of all important biological processes,
      including development, differentiation, and cancer. Although remarkable progress
      has been made in deciphering the mechanisms used by miRNAs to regulate
      translation, many contradictory findings have been published that stimulate
      active debate in this field. Here we contribute to this discussion in three ways.
      First, based on a comprehensive analysis of the existing literature, we
      hypothesize a model in which all proposed mechanisms of microRNA action coexist,
      and where the apparent mechanism that is detected in a given experiment is
      determined by the relative values of the intrinsic characteristics of the target
      mRNAs and associated biological processes. Among several coexisting miRNA
      mechanisms, the one that will effectively be measurable is that which acts on or
      changes the sensitive parameters of the translation process. Second, we have
      created a mathematical model that combines nine known mechanisms of miRNA action
      and estimated the model parameters from the literature. Third, based on the
      mathematical modeling, we have developed a computational tool for discriminating
      among different possible individual mechanisms of miRNA action based on
      translation kinetics data that can be experimentally measured (kinetic
      signatures). To confirm the discriminatory power of these kinetic signatures and
      to test our hypothesis, we have performed several computational experiments with
      the model in which we simulated the coexistence of several miRNA action
      mechanisms in the context of variable parameter values of the translation.

PMID- 22850427
TI  - Contribution of foods consumed away from home to energy intake in Brazilian urban
      areas: the 2008-9 Nationwide Dietary Survey.
AB  - The objectives of the present study were to estimate the dietary contribution of
      away-from-home food consumption, to describe the contribution of away-from-home
      foods to energy intake, and to investigate the association between eating away
      from home and total energy intake in Brazilian urban areas. In the first
      Brazilian Nationwide Dietary Survey, conducted in 2008-9, food records were
      collected from 25 753 individuals aged 10 years or older, living in urban areas
      of Brazil. Foods were grouped into thirty-three food groups, and the mean energy
      intake provided by away-from-home food consumption was estimated. Linear
      regression models were used to evaluate the association between away-from-home
      food consumption and total energy intake. All analyses considered the sample
      design effect. Of the total population, 43 % consumed at least one food item away
      from home. The mean energy intake from foods consumed away from home was 1408 kJ
      (337 kcal), averaging 18 % of total energy intake. Eating away from home was
      associated with increased total energy intake, except for men in the highest
      income level. The highest percentage of away-from-home energy sources was for
      food with a high content of energy, such as alcoholic beverages (59 %), baked and
      deep-fried snacks (54 %), pizza (42 %), soft drinks (40 %), sandwiches (40 %),
      and sweets and desserts (30 %). The consumption of foods away from home was
      related to a greater energy intake. The characterisation of away-from-home food
      habits is necessary in order to properly design strategies to promote healthy
      food consumption in the away-from-home environment.

PMID- 22850424
TI  - Stiffened yeast telomerase RNA supports RNP function in vitro and in vivo.
AB  - The 1157-nt Saccharomyces cerevisiae telomerase RNA, TLC1, in addition to
      providing a 16-nt template region for reverse transcription, has been proposed to
      act as a scaffold for protein subunits. Although accessory subunits of the
      telomerase ribonucleoprotein (RNP) complex function even when their binding sites
      are relocated on the yeast telomerase RNA, the physical nature of the RNA
      scaffold has not been directly analyzed. Here we explore the structure-function
      organization of the yeast telomerase RNP by extensively stiffening the three long
      arms of TLC1, which connect essential and important accessory protein subunits
      Ku, Est1, and Sm(7), to its central catalytic hub. This 956-nt triple-stiff-arm
      TLC1 (TSA-T) reconstitutes active telomerase with TERT (Est2) in vitro.
      Furthermore, TSA-T functions in vivo, even maintaining longer telomeres than TLC1
      on a per RNA basis. We also tested functional contributions of each stiffened arm
      within TSA-T and found that the stiffened Est1 and Ku arms contribute to telomere
      lengthening, while stiffening the terminal arm reduces telomere length and
      telomerase RNA abundance. The fact that yeast telomerase tolerates significant
      stiffening of its RNA subunit in vivo advances our understanding of the
      architectural and functional organization of this RNP and, more broadly, our
      conception of the world of lncRNPs.

PMID- 22850426
TI  - Alkaptonuria is a novel human secondary amyloidogenic disease.
AB  - Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of
      homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation
      that produces a HGA-melanin ochronotic pigment, of unknown composition. There is
      no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis.
      Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid
      presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland)
      and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was
      examined using immunofluorescence and their levels were evaluated in the
      patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to
      evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular
      tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co
      localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits
      assessed secondary type of amyloidosis. High levels of SAA and SAP were found in
      AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of
      patients' abdominal fat and salivary gland. AKU is the second pathology after
      Parkinson's disease where amyloid is associated with a form of melanin. Aberrant
      expression of proteins involved in amyloidogenesis has been found in AKU cells.
      Our findings on alkaptonuria as a novel type II AA amyloidosis open new important
      perspectives for its therapy, since methotrexate treatment proved to
      significantly reduce in vitro HGA-induced A-amyloid aggregates.

PMID- 22850428
TI  - Radical SAM enzymes and radical enzymology.

PMID- 22850429
TI  - The prevalence of celiac disease in the United States.
AB  - OBJECTIVES: The prevalence of celiac disease (CD) in the United States is
      unknown. We sought to estimate CD prevalence nationwide by using a nationally
      representative sample. METHODS: This study included 7,798 persons aged 6 years or
      older who participated in the National Health and Nutrition Examination Survey
      2009-2010. Serum samples from all participants were tested for immunoglobulin A
      (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for
      IgA endomysial antibodies. Information about prior diagnosis of CD and use of a
      gluten-free diet (GFD) was obtained by direct interview. CD was defined as having
      either double-positive serology (serologically diagnosed CD) or a reported
      diagnosis of CD by a doctor or other health-care professional and being on a GFD
      (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29
      of whom were unaware of their diagnosis. Median age was 45 years (interquartile
      range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence
      of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%),
      with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55
      participants reported following a GFD, which corresponded to a prevalence of
      0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United
      States was 0.71% (1 in 141), similar to that found in several European countries.
      However, most cases were undiagnosed. CD was rare among minority groups but
      affected 1% of non-Hispanic whites. Most persons who were following a GFD did not
      have a diagnosis of CD.

PMID- 22850430
TI  - Postoperative health-care utilization in Crohn's disease: the impact of
      specialist care.
AB  - OBJECTIVES: Crohn's disease (CD) patients frequently require surgery. We sought
      to characterize postoperative health-care utilization and its impact on outcomes.
      METHODS: We assembled a population-based cohort of CD patients who underwent
      first surgery in Ontario, Canada, between 1996 and 2009. We compared intra
      individual preoperative and postoperative health-care utilization and
      characterized utilization of early postoperative gastrointestinal care (EPGIC)
      and its impact on health outcomes. RESULTS: For the 2,943 CD patients who
      underwent surgery, the 5-year risk of recurrent surgery was 26%. In the 5th
      postoperative year, the average annual number of inflammatory bowel disease (IBD)
      related clinic visits, emergency department visits, endoscopy procedures,
      radiological procedures, and hospitalizations decreased by 62, 62, 82, 78, and
      89% compared with prior to surgery. Regional utilization of EPGIC varied between
      18 and 62% and correlated with the number of gastroenterologists within a
      regional local health integration network (rho=0.71; P=0.006). EPGIC was
      associated with reduced risk of late postoperative CD-related hospitalizations
      (at least 1 year after surgery; adjusted incidence ratio (IRR), 0.82; 95%
      confidence interval (CI): 0.72-0.94). Other predictors of late hospitalizations
      included having an emergency department visit within 6 months (adjusted IRR,
      2.60; 95% CI: 2.21-3.05), lower income, and higher comorbidity. Individuals
      residing in regions with high aggregate EPGIC utilization experienced lower rates
      of hospitalization compared with those in regions with low utilization (adjusted
      IRR, 0.83; 95% CI: 0.70-0.95). CONCLUSIONS: IBD-related health-care utilization
      decreased significantly up to 5 years following surgery. EPGIC may reduce late CD
      related hospitalizations following surgery.

PMID- 22850431
TI  - Immunochemical fecal occult blood testing is equally sensitive for proximal and
      distal advanced neoplasia.
AB  - OBJECTIVE: Fecal immunochemical testing (FIT) is increasingly used for colorectal
      cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in
      invitational population screening measured against colonoscopy. METHODS:
      Participants (50-75 years) in an invitational primary colonoscopy screening
      program were asked to complete one sample FIT before colonoscopy. We estimated
      FIT sensitivity, specificity, and predictive values in detecting CRC and advanced
      neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75
      (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with,
      respectively, 10, 15 and 20 MUg Hb/g feces. RESULTS: A total of 1,256
      participants underwent a FIT and screening colonoscopy. Advanced neoplasia was
      detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121
      (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had
      CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including
      1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29
      47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of
      93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and
      negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95%
      CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced
      neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were
      33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a
      positive test result. The sensitivity and specificity of FIT100 were for advanced
      neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI:
      36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced
      neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for
      proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75
      (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml. DISCUSSION: Nine
      out of ten screening participants with CRC and four out of ten with advanced
      neoplasia will be detected using one single FIT at low cutoff. Sensitivity in
      detecting proximal and distal advanced neoplasia is comparable.

PMID- 22850432
TI  - The integer quantum Hall effect of a square lattice with an array of point
      defects.
AB  - The electronic properties of a square lattice under an applied perpendicular
      magnetic field in the presence of impurities or vacancies are investigated by the
      tight-binding method including up to second nearest neighbor interactions. These
      imperfections result in new gaps and bands in the Hofstadter butterfly even when
      the second order interactions break the bipartite symmetry. In addition, the
      whole spectrum of the Hall conduction is obtained by the Kubo formula for the
      corresponding cases. The results are in accordance with the Thouless-Kohmoto
      Nightingale-den Nijs integers when the Fermi energy lies in an energy gap. We
      find that the states due to the vacancies or impurities with small hopping
      constants are highly localized and do not contribute to the Hall conduction.
      However, the impurities with high hopping constants result in new Hall plateaus
      with constant conduction of sigma(xy) =+/- e(2)/h, since high hopping constants
      increase the probability of an electron contributing to the conduction.

PMID- 22850433
TI  - p21 and Notch signalings in the persistently altered vagina induced by neonatal
      diethylstilbestrol exposure in mice.
AB  - Female reproductive organs show organ-specific morphological changes during
      estrous cycles. Perinatal exposure to natural and synthetic estrogens including
      diethylstilbestrol (DES) or estrogenic chemicals induces estrogen-independent
      persistent proliferation of vaginal epithelium in mice. To understand the
      underlying mechanism of the estrogen-independent persistent vaginal changes
      induced by perinatal DES exposure, we examined global gene expressions in the
      vaginae of ovariectomized adult mice exposed neonatally to DES using a
      microarray. The cell cycle-related gene, p21, a cyclin-dependent kinase
      inhibitor, showed upregulation in the vagina, and p21 protein was localized in
      the basal layer of the vaginal epithelium in mice exposed neonatally to DES and
      an estrogen receptor alpha agonist, propyl pyrazole triol (PPT). The expressions
      of Notch receptors and Notch ligands were unchanged; however, the mRNAs of hairy
      related basic helix-loop-helix (bHLH) transcription factor genes, Hes1, Hey1 and
      Heyl were persistently downregulated in the vagina, indicating estrogen
      independent epithelial cell proliferation in mice exposed neonatally to DES and
      PPT.

PMID- 22850434
TI  - Temperament, character and serotonin activity in the human brain: a positron
      emission tomography study based on a general population cohort.
AB  - BACKGROUND: The psychobiological model of personality by Cloninger and colleagues
      originally hypothesized that interindividual variability in the temperament
      dimension 'harm avoidance' (HA) is explained by differences in the activity of
      the brain serotonin system. We assessed brain serotonin transporter (5-HTT)
      density in vivo with positron emission tomography (PET) in healthy individuals
      with high or low HA scores using an 'oversampling' study design. Method Subjects
      consistently in either upper or lower quartiles for the HA trait were selected
      from a population-based cohort in Finland (n = 2075) with pre-existing
      Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of
      psychiatric and somatic disorders were included in the matched high- and low-HA
      groups. The main outcome measure was regional 5-HTT binding potential (BPND) in
      high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4
      methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was
      correlated with other TCI dimensions. RESULTS: 5-HTT BPND did not differ between
      high- and low-HA groups in the midbrain or any other brain region. This result
      remained the same even after adjusting for other relevant TCI dimensions. Higher
      5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'.
      CONCLUSIONS: This study does not support an association between the temperament
      dimension HA and serotonin transporter density in healthy subjects. However, we
      found a link between high serotonin transporter density and high 'self
      directedness' (ability to adapt and control one's behaviour to fit situations in
      accord with chosen goals and values). We suggest that biological factors are more
      important in explaining variability in character than previously thought.

PMID- 22850435
TI  - Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and
      related behavioural changes via cGMP/PKG dependent pathway.
AB  - Phosphodiesterase 2 (PDE2) is an enzyme responsible for hydrolysis of cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to
      restrict intracellular signalling of these second messenger molecules. This study
      investigated how PDE2 inhibitor Bay 60-7550 affects the dysregulated
      glucocorticoid signalling in neuronal cells and regulates depressive behaviours
      after chronic stress in mice. We found that exposure of hippocampal neurons to
      corticosterone resulted in time- and concentration-dependent increases in PDE2
      expression. These intriguing findings were confirmed in the hippocampal cell line
      HT-22. After corticosterone exposure for 24 h, HT-22 cells showed a concentration
      dependent increase in mRNA levels for PDE2 subtypes, PDE2A1 and 2A3, as well as
      for the total PDE2A protein expression. Bay 60-7550 was found to reverse the cell
      lesion induced by corticosterone (50 MUm). This neuroprotective effect was
      blocked by pretreatment with protein kinase G inhibitor KT5823, but not protein
      kinase A inhibitor H89, suggesting the involvement of cGMP-dependent signalling.
      Although Bay 60-7550 treatment for 24 h did not change the levels of
      phosphorylated mitogen-activated protein kinases ERK1/2 (pERK) and phosphorylated
      cAMP response element-binding protein (pCREB), it down-regulated pERK at 2 h and
      up-regulated a CREB co-activator, CREB-binding protein, at 24 h. Both of these
      effects were blocked by KT 5823. Furthermore, Bay 60-7550 reversed corticosterone
      induced down-regulation of brain-derived neurotrophic factor protein levels 24 h
      after corticosterone exposure. In behavioural testing, Bay 60-7550 produced
      antidepressant-like effects and reduced corticosterone levels in stressed mice,
      further supporting the involvement of a PDE2-dependent pathway in mediating Bay
      60-7550's effect during stress hormone insults.

PMID- 22850436
TI  - State background checks for gun purchase and firearm deaths: an exploratory
      study.
AB  - OBJECTIVE: This study examines the relationship between the types of background
      information check required by states prior to firearm purchases, and firearm
      homicide and suicide deaths. METHODS: Negative binomial models are used to
      analyze state-level data for homicides and suicides in the U.S. from 1996 to
      2005. Data on types of background information are retrieved from the Surveys of
      State Procedures Related to Firearm Sales, and the violent death data are from
      the WISQARS. Several other state level factors were controlled for. RESULTS: More
      background checks are associated with fewer homicide (IRR:0.93, 95% CI:0.91-0.96)
      and suicide (IRR:0.98, 95% CI:0.96-1.00) deaths. Firearm homicide deaths are
      lower when states have checks for restraining orders (IRR:0.87, 95% CI:0.79-0.95)
      and fugitive status (IRR:0.79, 95% CI:0.72-0.88). Firearm suicide deaths are
      lower when states have background checks for mental illness (IRR:0.96, 95%
      CI:0.92-0.99), fugitive status (IRR:0.95, 95% CI:0.90-0.99) and misdemeanors
      (IRR:0.95, 95% CI:0.92-1.00). It does not appear that reductions in firearm
      deaths are offset by increases in non-firearm violent deaths. CONCLUSIONS: More
      extensive background checks prior to gun purchase are mostly associated with
      reductions in firearm homicide and suicide deaths. Several study limitations are
      acknowledged, and further research is called for to ascertain causality.

PMID- 22850438
TI  - Pt nanoparticle-dispersed graphene-wrapped MWNT composites as oxygen reduction
      reaction electrocatalyst in proton exchange membrane fuel cell.
AB  - Chemical and electrical synergies between graphite oxide and multiwalled carbon
      nanotube (MWNT) for processing graphene wrapped-MWNT hybrids has been realized by
      chemical vapor deposition without any chemical functionalization. Potential of
      the hybrid composites have been demonstrated by employing them as electrocatalyst
      supports in proton exchange membrane fuel cells. The defects present in the
      polyelectrolyte, which have been wrapped over highly dispersed MWNT, act as
      anchoring sites for the homogeneous deposition of platinum nanoparticles. Single
      cell proton exchange membrane fuel cells show that the power density of the
      hybrid composite-based fuel cells is higher compared to the pure catalyst-support
      based fuel cells, because of enhanced electrochemical reactivity and good surface
      area of the nanocomposites.

PMID- 22850439
TI  - Photochemical dynamics of E-iPr-furylfulgide.
AB  - As an important theoretical step towards unraveling the mechanistic details of
      the photochemical switching processes in molecules of the fulgide type, we
      carried out a large-scale, full-dimensional computational study of the ring
      closure reaction of E-iPr-furylfulgide. Simulated static UV spectra and
      femtosecond transient spectra are in good agreement with their experimental
      counterparts. Using surface-hopping photodynamics simulations, we identify three
      major de-excitation pathways and their interplay. The dominant photochemical
      pathway (70% of the trajectories) allows for ring closure, while the two minor
      pathways involve E-Z double bond isomerization rather than cyclization. The
      relative abundance of the pathways is rationalized by arguments linking structure
      with dynamics. It should be emphasized, however, that the distinction into three
      pathways is only a simplified interpretational model, since the actual dynamical
      trajectories do not strictly follow these idealized pathways but often show mixed
      behaviour, evolving along two or three of them during the course of the
      simulation.

PMID- 22850437
TI  - NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor
      activation induced by d-amphetamine in animal models of schizophrenia.
AB  - The most widely validated animal models of the positive, negative and cognitive
      symptoms of schizophrenia involve administration of d-amphetamine or the open
      channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and
      ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII),
      an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate
      (NAAG) and reduces positive and negative behaviors induced by PCP in several of
      these models. NAAG is an agonist at the metabotropic glutamate receptor 3
      (mGluR3). Polymorphisms in this receptor have been associated with expression of
      schizophrenia. This study aimed to determine whether two different NAAG peptidase
      inhibitors are effective in dopamine models, whether their efficacy was
      eliminated in GCPII knockout mice and whether the efficacy of these inhibitors
      extended to MK-801-induced cognitive deficits as assessed using the novel object
      recognition test. ZJ43 blocked motor activation when given before or after d
      amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA),
      another potent NAAG peptidase inhibitor, also reduced motor activation induced by
      PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2
      PMPA also blocked MK-801-induced deficits in novel object recognition when given
      before, but not after, the acquisition trial. The group II mGluR antagonist
      LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2
      PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By
      bridging the dopamine and glutamate theories of schizophrenia with two
      structurally different NAAG peptidase inhibitors and demonstrating their efficacy
      in blocking MK-801-induced memory deficits, these data advance the concept that
      NAAG peptidase inhibition represents a potentially novel antipsychotic therapy.

PMID- 22850440
TI  - 'Diagnostic mode' improves adherence to the home blood pressure measurement
      schedule.
AB  - BACKGROUND: The accuracy of home blood pressure measurement (HBPM) depends on
      adherence to the measurement schedule. We investigated the number of deviations
      from the requested schedule using an HBPM device equipped with a diagnostic mode
      that only allows patients to take a fixed number of BP readings at preset times.
      METHODS: We randomized patients to measure their BP as recommended by the
      European Society of Hypertension guideline in either the usual mode or the
      diagnostic mode. RESULTS: A total of 135 patients were included, mean age 54.4 +/
      13.6 years, 57 (42.2%) men, with a mean systolic BP of 147.0 +/- 18.4 mmHg and a
      mean diastolic BP of 88.0 +/- 10.3 mmHg. In 66 patients, BP was measured in the
      diagnostic mode, whereas in 69 patients BP was measured in the usual mode. In the
      diagnostic mode, 40% of patients showed full adherence to the measurement
      schedule, compared with 23% of patients in the usual mode (P = 0.02). Unscheduled
      measurements were performed by 55% of patients measuring BP in the usual mode and
      none in the diagnostic mode. The number of patients who omitted readings was
      similar in the diagnostic and the usual mode (P = 0.9). Compared with scheduled
      readings only, 12% of patients measuring BP in the usual mode fell into a
      different BP category, whereas reclassification did not occur in patients using
      the diagnostic mode (P = 0.03). CONCLUSION: HBPM in the diagnostic mode almost
      doubled the number of patients with full adherence to the measurement schedule
      and eliminated the number of patients who were reclassified in a different BP
      category.

PMID- 22850441
TI  - A standardized phytopreparation from an Indian medicinal plant (Dalbergia sissoo)
      has antiresorptive and bone-forming effects on a postmenopausal osteoporosis
      model of rat.
AB  - OBJECTIVE: The aim of this study was to evaluate the skeletal effects of an
      extract made from the leaves and pods of Dalbergia sissoo (butanol-soluble
      standardized fraction [BSSF]) on ovariectomized rats, a model for postmenopausal
      osteopenia. METHODS: Adult Sprague-Dawley rats were ovariectomized and
      administered BSSF (50 and 100 mg/kg per day) or 17beta-estradiol orally for 12
      weeks. The sham-operated group and the ovariectomy + vehicle group served as
      controls. Bone microarchitecture, bone turnover markers (serum osteocalcin and C
      telopeptide fragment of collagen type I), biomechanical strength, new bone
      formation (based on mineral apposition rate and bone formation rate), and
      skeletal expressions of osteogenic and resorptive gene markers were studied.
      Uterine histomorphometry was used to assess estrogenicity. Bioactive marker
      compounds in BSSF were analyzed by high-performance liquid chromatography. One
      way analysis of variance was used to test the significance of effects. RESULTS:
      In comparison with ovariectomized rats treated with vehicle, BSSF treatment in
      ovariectomized rats resulted in an improved trabecular microarchitecture of the
      long bones, increased biomechanical strength parameters of the vertebra and
      femur, decreased bone turnover markers (osteocalcin and type I collagen) and
      expression of skeletal osteoclastogenic genes, and increased new bone formation
      and expression of osteogenic genes in the femur. Overall, the osteoprotective
      effects of BSSF were comparable to those of 17beta-estradiol. BSSF did not
      exhibit uterine estrogenicity. Analysis of marker compounds revealed the presence
      of osteogenic methoxyisoflavones, including caviunin 7-O-[beta-D-apiofuranosyl-(1
      >6)-beta-D-glucopyranoside] (a novel compound), biochanin A, and pratensin.
      CONCLUSIONS: Oral doses of BSSF in the preclinical setting are effective in
      preventing estrogen deficiency-induced bone loss by dual action: inhibition of
      bone resorption and stimulation of new bone formation.

PMID- 22850442
TI  - Low-dose rosuvastatin improves the functional and morphological markers of
      atherosclerosis in asymptomatic postmenopausal women with dyslipidemia.
AB  - OBJECTIVE: Several large-scale studies have shed light on the primary preventive
      efficacy of statins against atherosclerotic diseases in the course of treatment
      of dyslipidemia. However, this efficacy in the management of dyslipidemia in
      relatively low-risk patients, particularly in women, has not been clarified.
      Here, we investigated the efficacy of dyslipidemia treatment with a statin on
      three indices that are widely used to assess atherosclerosis in postmenopausal
      women: carotid intima-media thickness (CIMT), arterial stiffness index beta of
      the common carotid artery (carotid stiffness beta), and brachial artery pulse
      wave velocity (baPWV). METHODS: The study enrolled 51 postmenopausal women aged
      55 years or older with dyslipidemia. The participants were randomly divided into
      two treatment groups and received a single daily administration of 2.5 mg of
      rosuvastatin or no statin therapy as control. RESULTS: At baseline, the groups
      did not significantly differ with regard to the three indices. At the third and
      12th months of treatment, both carotid stiffness beta and baPWV values were
      significantly lower than those of the control group. As for CIMT, the value was
      significantly lower in the statin group than in the control group at 12 months of
      treatment. These changes were in conjunction with a significant decrease in low
      density lipoprotein cholesterol. Interestingly, changes in CIMT during the 12
      month period were significantly correlated with changes in high-sensitivity C
      reactive protein during the 3-month period independently of lipid profile.
      CONCLUSIONS: The potent statin improves baPWV and carotid stiffness beta, in
      addition to CIMT (surrogate markers of coronary artery disease), in
      postmenopausal women with low-risk dyslipidemia. Further studies to clarify the
      common mechanisms underlying the link between cholesterol-lowering therapy and
      atherosclerosis in postmenopausal women are required.

PMID- 22850444
TI  - Inhibition of NF-kappaB activation is associated with anti-inflammatory and anti
      apoptotic effects of Ginkgolide B in a mouse model of cerebral
      ischemia/reperfusion injury.
AB  - Ginkgolide B (GB) has potent neuroprotective effects against ischemia-induced
      brain injury in vivo and in vitro. However, the underlying mechanisms of GB's
      neuroprotection remain poorly understood. Excessive inflammation and apoptosis
      contribute to the pathogenesis of ischemic brain damage, and NF-kappaB is
      considered to be a key player in these processes. In the present study, we
      examined the detailed mechanisms underlying the inhibitory effects of GB on
      inflammatory and apoptotic responses induced by focal cerebral
      ischemia/reperfusion (I/R). Transient middle cerebral artery occlusion (tMCAO)
      model was produced by using an intraluminal filament technique in mice. GB (10,
      20 and 40 mg/kg) was administered intravenously (i.v.) 2h after MCAO. The results
      demonstrated that MCAO-induced cerebral injury was associated with an
      upregulation of p-IKK, p-IkappaB-alpha and degradation of IkappaB-alpha,
      indicating of NF-kappaB activation. Meanwhile activation of microglial and
      increases in levels of TNF-alpha, IL-1beta and iNOS were observed. Furthermore
      upregulation of the expression of NF-kappaB target gene p53 and p53 downstream
      gene Bax, but downregulation of Bcl-2 and activation of caspase-3 were found. GB
      treatment showed marked reduction in infarction volume, brain edema and
      neurological deficits. GB also inhibited I/R induced NF-kappaB, microglia
      activation and production of pro-inflammatory cytokines. We also demonstrated
      that GB reduced Bax protein levels and increased Bcl-2 protein levels in the post
      ischemic brains. These results suggest that GB's neuroprotection is attributable
      to its anti-inflammatory and anti-apoptotic effect through inhibition of NF
      kappaB.

PMID- 22850443
TI  - Bone resorption and fracture across the menopausal transition:  the Study of
      Women's Health Across the Nation.
AB  - OBJECTIVE: Bone turnover markers (BTMs) predict fracture in older women, whereas
      data on younger women are lacking. To test the hypothesis that BTMs measured
      before and after menopause predict fracture risk, we performed a cohort study of
      2,305 women. METHODS: Women attended up to nine clinic visits for an average of
      7.6 +/- 1.6 years; all were aged 42 to 52 years and were premenopausal or early
      perimenopausal at baseline. Incident fractures were self-reported. Serum
      osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were
      measured at baseline. NTX was measured at each annual follow-up. Interval
      censored survival models or generalized estimating equations were used to test
      whether baseline BTMs and changes in NTX, respectively, were associated with
      fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs.
      RESULTS: Women who experienced fractures (n = 184) had about a 10% higher
      baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per
      liter per nanomole of creatinine per liter; P = 0.001), but there was no
      difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density
      (BMD) measured premenopausally was associated with a higher fracture risk during
      menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than
      the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46;
      95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD
      (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61
      6.01), compared with women with lower NTX and higher BMD. Women whose NTX
      increased more than the median had a higher risk of fracture (odds ratio, 1.51;
      95% CI, 1.08-2.10). Women who had baseline NTX greater than the median
      experienced greater loss of spine and hip BMD. CONCLUSIONS: A higher urinary NTX
      excretion measured before menopause and across menopause is associated with a
      higher risk of fracture. Our results are consistent with the pathophysiology of
      transmenopausal changes in bone strength.

PMID- 22850445
TI  - Regulatory T cell defects in adult autoimmune hepatitis.

PMID- 22850446
TI  - Dendron-modified surfaces provide an ideal environment for stem-loop DNA probes.
AB  - Specificity and sensitivity are important factors affecting DNA microarrays. Stem
      loop DNA probes (SLPs) can be more specific in their recognition of target
      sequences than linear DNA probes, but unless they are carefully designed, surface
      interactions can disrupt the native stem-loop structure. In this study, we show
      how dendron-modified surfaces with well-defined, uniform spacing of aldehyde
      chemical functionalities offer an ideal substrate to immobilize SLPs and use them
      to detect nucleic acid targets. The mesospacing provided by the dendron-modified
      surfaces produces a solution-like environment that allows the SLPs to detect
      target nucleic acids at concentrations as low as 1pM in concentration.

PMID- 22850447
TI  - Identification and elimination of heterophilic antibody interference during
      antibody pair screening.
AB  - High background interference during the antibody pair screening process is
      inevitable. In this study, we found that the high background was associated with
      heterophilic antibody interference introduced by the application of ascites
      derived monoclonal antibodies when conducting large-scale antibody pair screening
      against different proteins. To eliminate antibody-associated heterophilic
      antibody interference, both blocking with mouse normal sera and antigen-mediated
      affinity chromatography were used, resulting in significant improvement in
      pairing performance and in antibody pair screening efficiency.

PMID- 22850448
TI  - Simvastatin reduces endothelial NOS: caveolin-1 ratio but not the phosphorylation
      status of eNOS in vivo.
AB  - In vivo evidence for the pleiotropic effects of simvastatin on the nitric oxide
      synthase system is limited. AIMS: To determine if simvastatin can affect the
      endothelial nitric oxide synthase cascade. METHODS: New Zealand white rabbits
      (n=15) were divided: Group 1 (control) was fed a normal rabbit diet; Group 2 (MC)
      received a normal rabbit diet with 1% methionine (M) plus 0.5% cholesterol (C)
      and 5% peanut oil (atherogenic diet); Group 3 received the same diet as the MC
      group plus 5 mg/kg/ day simvastatin (S) orally (MCS). After 4 weeks, the
      abdominal aorta was collected and analyzed. RESULTS: Total cholesterol (TC) and
      total homocysteine (tHcy) were not significantly different between MCS and MC.
      Endothelial function was only reduced in MC (p<0.05). Although eNOS significantly
      increased in MC and MCS (p<0.01), simvastatin treatment significantly reduced
      endothelial caveolin-1 by 35% (p=0.038), causing a 2.5-fold (p=0.026) increase in
      the eNOS: caveolin-1 ratio. The phosphorylation of eNOS at the threonine 495 site
      or serine 1177 site was not affected by diet or treatment; however, a positive
      correlation between the two phosphorylation sites was observed (r(2)= 0.5,
      p=0.01). CONCLUSION: in vivo pleiotropic effects of statin therapy include
      decreasing endothelial caveolin-1. Other therapies designed to affect eNOS
      phosphorylation in vivo might be useful in further preventing CVD.

PMID- 22850460
TI  - Magnetic Kronig-Penney-type graphene superlattices: finite energy Dirac points
      with anisotropic velocity renormalization.
AB  - We study the energy band structure of magnetic graphene superlattices with delta
      function magnetic barriers and zero average magnetic field. The dispersion
      relation obtained using the T-matrix approach shows the emergence of an infinite
      number of Dirac-like points at finite energies, while the original Dirac point is
      still located at the same place as that for pristine graphene. The carrier group
      velocity at the original Dirac point is isotropically renormalized, but at finite
      energy Dirac points it is generally anisotropic. An asymmetry in the width
      between the wells and the barriers of the periodic potential induces a shift of
      the original Dirac point in the zero-energy plane, keeping the velocity
      renormalization isotropic.

PMID- 22850461
TI  - Detection and phylogenetic analysis of hepatitis E viruses from mongooses in
      Okinawa, Japan.
AB  - Hepatitis E virus (HEV) infection has previously been reported in wild mongooses
      on Okinawa Island; to date however, only one HEV RNA sequence has been identified
      in a mongoose. Hence, this study was performed to detect HEV RNA in 209 wild
      mongooses on Okinawa Island. Six (2.9%) samples tested positive for HEV RNA.
      Phylogenetic analysis revealed that 6 HEV RNAs belonged to genotype 3 and were
      classified into groups A and B. In group B, mongoose-derived HEV sequences were
      very similar to mongoose HEV previously detected on Okinawa Island, as well as to
      those of a pig. This investigation emphasized the possibility that the mongoose
      is a reservoir animal for HEV on Okinawa Island.

PMID- 22850462
TI  - A multiple-instance learning framework for diabetic retinopathy screening.
AB  - A novel multiple-instance learning framework, for automated image classification,
      is presented in this paper. Given reference images marked by clinicians as
      relevant or irrelevant, the image classifier is trained to detect patterns, of
      arbitrary size, that only appear in relevant images. After training, similar
      patterns are sought in new images in order to classify them as either relevant or
      irrelevant images. Therefore, no manual segmentations are required. As a
      consequence, large image datasets are available for training. The proposed
      framework was applied to diabetic retinopathy screening in 2-D retinal image
      datasets: Messidor (1200 images) and e-ophtha, a dataset of 25,702 examination
      records from the Ophdiat screening network (107,799 images). In this application,
      an image (or an examination record) is relevant if the patient should be referred
      to an ophthalmologist. Trained on one half of Messidor, the classifier achieved
      high performance on the other half of Messidor (A(z)=0.881) and on e-ophtha
      (A(z)=0.761). We observed, in a subset of 273 manually segmented images from e
      ophtha, that all eight types of diabetic retinopathy lesions are detected.

PMID- 22850463
TI  - Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced
      neurotoxicity in rats.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder with a
      spectrum of cognitive, behavioral, and motor abnormalities. The mitochondrial
      toxin 3-nitropropionic acid (3-NP) effectively induces specific behavioral
      changes, primarily manifested as prepulse inhibition (PPI) deficit of acoustic
      startle stimuli, and selective striatal lesions in rats and primates mimicking
      those in HD. The implications of nitric oxide in a variety of neurodegenerative
      diseases attract attention to study the possible role of flavonoids in
      interaction with nitric oxide pathways involved in HD. The present study
      investigates the potential effect of hesperidin, a flavanone group member, on 3
      NP-induced behavioral, neurochemical, histopathological and cellular changes.
      Systemic administration of 3-NP to rats for 5 days (20 mg/kg) caused reduction of
      locomotor activity by days 2 and 5, 55% deficit of PPI response, elevation of
      cortical, striatal and hippocampal malondialdehyde (MDA) levels by 63%, 41% and
      56%, reduction of respective catalase activity by 50%. Immunohistochemical
      staining of cortices, striata and hippocampi showed patches of iNOS positive
      cells. Electron microscopic ultrastructural examination showed marked
      mitochondrial swelling, perivascular edema and shrunken nerve cells. Pretreatment
      with hesperidin (100 mg/kg) ahead of 3-NP prevented any changes of locomotor
      activity or PPI response, slightly increased cortical, striatal and hippocampal
      MDA levels by 10% and reduced respective catalase activity by 22%, 20% and 5%.
      Only few iNOS positive cells were detected in sections from rats pretreated with
      hesperidin which also reduced cellular abnormalities induced by 3-NP. This study
      suggests a potential neuroprotective role of hesperidin against 3-NP-induced
      Huntington's disease-like manifestations. Such neuroprotection can be referred to
      its antioxidant and anti-inflammatory activities.

PMID- 22850465
TI  - The rat as an animal model for fetoplacental development: a reappraisal of the
      post-implantation period.
AB  - Following implantation in rodents, the uterine stromal fibroblasts differentiate
      into densely packed decidual cells. This process, called decidualization, is well
      orchestrated and progresses both antimesometrially and mesometrially, creating
      two regions with distinctive cellular morphologies. In addition, subsequent
      placental development is dependent on the invasion of the trophoblast, the
      process intimately linked to the endometrial tissue remodelling and depending
      largely on the environment created by the decidua; this phenomenon is crucial for
      the establishment and maintenance of pregnancy. The key mechanisms underlying the
      maternal tissue remodelling and trophoblast invasion remain poorly understood.
      The rat, just like human beings, exhibits a highly invasive type of placental
      development, the haemochorial placentation. For obvious ethical reasons, the
      studies of endometrial tissue remodelling throughout pregnancy in humans are
      greatly limited. Although the rat differs somewhat from humans with regards to
      the implantation process, it is an appropriate model for studying the mechanisms
      of decidualization as well as subsequent remodelling of the uterine tissues and
      fetoplacental development. As decidual remodelling is very closely linked to
      placentation and the maternal-fetal interactions in the rat show several
      important similarities to human placentation, the morphological alterations
      occurring during the post-implantation period in the rat have been addressed in
      the present review.

PMID- 22850466
TI  - Effects of hexavalent chromium on reproductive functions of male adult rats.
AB  - Hexavalent chromium is an environmental contaminant which may be associated with
      reproductive abnormalities in male rats. In the present study, we examined the
      effect of hexavalent chromium on male reproductive function of rats. Male Wistar
      rats received a daily intraperitoneal injection of potassium dichromate (1 or 2
      mg/kg body weight) for fifteen consecutive days. A decrease in testis weight and
      an increase in seminal vesicles and prostate weights were demonstrated after
      chromium treatment. Moreover, a dose-dependent increase in blood and testis
      chromium levels as well as an increase in FSH and a decrease in LH and
      testosterone serum levels were detected in treated rats. Histological analysis
      revealed pronounced morphological alterations with enlarged intracellular spaces,
      tissue loosening and dramatic loss of gametes in the lumen of the seminiferous
      tubules of treated rats. In addition, a decreased sperm motility and number of
      epididymal spermatozoa together with an increased sperm abnormality rate was
      found in chromium-treated rats in comparison to controls. In rats receiving the
      higher chromium dose, histological images presented considerably increased areas
      filled with seminal vesicle and prostate secretions. The mucosal crypts of
      seminal vesicles and the typical invaginations of prostate were altered. The
      results suggest that subacute treatment of potassium dichromate promotes
      reproductive system toxicity and affects testicular function of adult male rats.

PMID- 22850464
TI  - Monoamine oxidase A and A/B knockout mice display autistic-like features.
AB  - Converging lines of evidence show that a sizable subset of autism-spectrum
      disorders (ASDs) is characterized by increased blood levels of serotonin (5
      hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena
      remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by
      monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate
      isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels,
      particularly during early developmental stages. Here we show that both mutant
      lines exhibit numerous behavioural hallmarks of ASDs, such as social and
      communication impairments, perseverative and stereotypical responses, behavioural
      inflexibility, as well as subtle tactile and motor deficits. Furthermore, both
      MAOA and A/B KO mice displayed neuropathological alterations reminiscent of
      typical ASD features, including reduced thickness of the corpus callosum,
      increased dendritic arborization of pyramidal neurons in the prefrontal cortex
      and disrupted microarchitecture of the cerebellum. The severity of repetitive
      responses and neuropathological aberrances was generally greater in MAOA/B KO
      animals. These findings suggest that the neurochemical imbalances induced by MAOA
      deficiency (either by itself or in conjunction with lack of MAOB) may result in
      an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B
      KO mice may afford valuable models to help elucidate the neurobiological bases of
      these disorders and related neurodevelopmental problems.

PMID- 22850467
TI  - Localization of orexin A and orexin B in the porcine uterus.
AB  - The presence of orexins and their receptors in gonads indicate that these
      hormones participate in the control of reproductive functions. The aim of the
      study was to compare the expression of the prepro-orexin (PPO) gene in porcine
      endometrium and myometrium and the intensity of OXA- and OXB-immunoreactivity in
      the following uterine structures: endometrial glandular and luminal epithelium
      and stroma as well as the myometrial longitudinal and circular muscles during the
      four stages (days 2-3, 10-12, 14-16, 17-19) of the estrous cycle. The highest
      expression of PPO mRNA was observed in the endometrium and the myometrium on days
      14-16 of the cycle. The expression of the PPO gene on days 2-3 was more
      pronounced in the myometrium than in the endometrium, whereas on days 17-19 the
      gene expression was markedly higher in the endometrium. The OXA signal intensity
      was highest on days 2-3 in the luminal epithelium and on days 2-3 and 10-12 in
      the stroma. In circular muscles of the myometrium, the highest immunoreactivity
      was found on days 2-3 and 10-12, while in longitudinal muscles on days 2-3. OXB
      immunoreactivity was highest on days 10-12 in longitudinal muscles, on days 17-19
      in glandular epithelium and stroma, and on days 10-12 and 14-16 in luminal
      epithelium. Our results suggest that orexin A and B are produced in the porcine
      uterus and that their release is dependent on the hormonal status of animals.

PMID- 22850468
TI  - Expression of peroxisome proliferator activated receptor (PPAR) genes in porcine
      endometrium exposed in vitro to IL-6 and INFgamma.
AB  - The aim of the present study was to examine the effects of interferon gamma
      (INFgamma) or interleukin 6 (IL-6) on gene expression of PPARs in the porcine
      endometrium on day 14 of the estrous cycle and pregnancy. Endometrial tissue (200
      210 mg), after 18 h of pre-incubation, was incubated for 6 or 12 h in the
      presence of INFgamma (5 or 50 ng/ml) or IL-6 (1 or 10 ng/ml). Gene expression was
      analyzed by quantitative real time RT-PCR. During the estrous cycle, neither
      INFgamma nor IL-6 affected PPARalpha and PPARbeta/delta transcript levels in the
      endometrium of the cyclic pigs incubated for 6 or 12 hours. The presence of
      INFgamma (5 ng/ml) significantly (p<0.05) increased PPARgamma1 gene expression in
      the tissue incubated for 12 h. During pregnancy, INFgamma (50 ng/ml)
      significantly (p<0.05) enhanced PPARalpha and PPARbeta/delta mRNA levels in the
      endometrium incubated for 6 h,  whereas IL-6 (1 or 10 ng/ml) did not change their
      expression at any incubation time. The effect of both cytokines on PPARgamma1
      transcript level differed and was dependent on the incubation time. We observed
      an inhibitory (after 6 h of incubation, p<0.0001) and a stimulatory (after 12 h
      of incubation, p<0.05) effect of INFgamma (5 ng/ml) or IL-6 (10 ng/ml) on
      PPARgamma1 gene expression. The present study indicates that INFgamma and IL-6
      modulate PPARs gene expression in the porcine endometrium during the estrous
      cycle and pregnancy. The effect depends on the reproductive status of animals and
      the length of in vitro incubation of endometrial tissue with the treatments.

PMID- 22850469
TI  - Effect of vitamin E on sperm number and testis histopathology of sodium arsenite
      treated rats.
AB  - The aims of this study were to investigate the adverse effects of sodium arsenite
      on the reproductive system of male rats as well as to examine whether vitamin E
      is able to ameliorate these effects. Adult rats were divided into four groups: 1/
      control, 2/ sodium arsenite (8 mg/kg/day), 3/ vitamin E (100 mg/kg/day), and 4/
      sodium arsenite +vitamin E group. Treatments were administered orally by gavage
      for eight weeks. After treatment, body and left testis weights were recorded and
      the testis was used for the histological analysis. Left cauda epididymis was used
      to count sperm number. Body and testis weight did not differ among the groups
      (p>0.05). A significant decrease (p<0.001) in sperm number and mean diameter of
      seminiferous tubules as well as a significant increase (p<0.001) in the mean
      diameter of seminiferous tubules' lumen were found in sodium arsenite group
      compared to those of controls. Sodium arsenite did not affect the morphology and
      diameter of spermatogonial nucleus (p>0.05). In the sodium arsenite + vitamin E
      group, vitamin E ameliorated (p<0.001) the adverse effects of sodium arsenite on
      sperm number as well as the diameters of tubule and lumen. In addition, the
      treatment of rats with vitamin E alone significantly (p<0.001) increased the
      diameter of seminiferous tubules and significantly (p<0.001) decreased
      seminiferous tubules' lumen compared to the control group. Vitamin E appeared to
      ameliorate the adverse effects of sodium arsenite on epididymal sperm number and
      some morphometrical parameters of the adult rat testis.

PMID- 22850470
TI  - Microarray profiling of secretory-phase endometrium from patients with recurrent
      miscarriage.
AB  - The aim of the present study was to identify differentially expressed genes and
      their related biological pathways in the secretory phase endometrium from
      patients with recurrent miscarriage (RM) and fertile subjects. Endometrial
      samples from RM and fertile patients were analyzed using the Affymetrix
      GeneChip(r) ST Array. The bioinformatic analysis using the Partek Genomic Suite
      revealed 346 genes (175 up-regulated and 171 down-regulated) that were
      differentially expressed in the endometrium of RM patients compared to the
      fertile subjects (fold change >=1.5, p<0.005). Validation step using quantitative
      real-time  polymerase chain reaction (qPCR) confirmed a similar expression
      pattern of four exemplary genes: one up-regulated gene (fibroblast growth factor
      9, FGF9) and three down-regulated genes: integrin beta3 (ITGB3), colony
      stimulating factor 1 (CSF1) and matrix-metalloproteinases 19 (MMP19). The Gene
      Set Enrichment Analysis (GSEA) and the Pathway Studio software have found 101
      signaling pathways (p<0.05) associated with the affected genes including the
      FGFR3 /signal transducer and activator of transcription (STAT) pathway and the
      CSF1R/STAT pathway. Cell adhesion, cell differentiation and angiogenesis were
      among biological processes indicated by this system. In conclusion, microarray
      technique is a useful tool to study gene expression in the secretory phase
      endometrium of RM patients. The differences in endometrial gene expressions
      between healthy and RM subjects contribute to an increase in our knowledge on
      molecular mechanisms of RM development and may improve the outcome of pregnancies
      in high-risk women with RM.

PMID- 22850471
TI  - Influence of the photoperiod on TGF-beta1 and p15 expression in hamster Leydig
      cells.
AB  - Adult hamsters exposed to short photoperiods show a marked atrophy of their
      internal reproductive organs, including a reduction in size, though not number of
      Leydig cells. Transforming growth factor-beta1 (TGF-beta1) is involved in the
      regulation of growth and proliferation of different cell types. The aim of the
      present study was to examine the influence of photoperiod on the protein and gene
      expression of TGF-beta1 and its receptors as well as gene expression of p15. The
      effect of TGF-beta1 on the expression of p15 in purified Leydig cells from
      regressed and non-regressed hamster testes was also tested. Protein and gene
      expression of TGF-beta1 was detected in both regressed and non-regressed testes.
      In contrast to the activin receptor-like kinase 1 (ALK-1), the TGF-beta1, the
      activin receptor-like kinase 5 (ALK-5) and the co-receptor endoglin all showed a
      greater basal expression in regressed than non-regressed hamster testes.
      Melatonin induced the TGF-beta1 mRNA expression in purified Leydig cells from non
      regressed testes. The p15 mRNA level was greater in regressed than non-regressed
      testes. A high dose of TGF-beta1 during a short incubation period increased the
      p15 mRNA level in Leydig cells from non-regressed testes. ALK-5 and mitogen
      activated protein kinase (MAPK) p38 might have played a role in this process. In
      regressed hamster testes, the p15 mRNA level increased due to a low dose of TGF
      beta1 after short incubation periods and to a high dose after longer incubation
      periods; in both instances, ALK-5, ERK 1/2 and p38 were involved. Collectively,
      these results suggest that the alterations in p15 expression, mediated by MAPK,
      are involved in the shift between the active and inactive states in hamster
      Leydig cells.

PMID- 22850472
TI  - Prognosis for clinical pregnancy and birth after transferring embryos derived
      from a cohort of incompletely mature oocytes at retrieval time.
AB  - The purpose of this retrospective study was to establish a prognosis for
      implantation, pregnancy and live birth rates in stimulated IVF cycles after
      transferring embryos derived from: 1/ retrieved immature oocytes that matured
      overnight in vitro (late mature group: LM); 2/ retrieved immature oocytes that
      matured overnight in vitro and were added to the embryos derived from retrieved
      mature oocytes (mixed embryos group: MX); and 3/ retrieved mature oocytes (mature
      group: M). The obtained implantation, clinical pregnancy and live birth rates for
      the LM group were: 5.6%, 11.4%, 11.4%; for the MX group were: 4.2%, 14.6%, 11.6%;
      and for the M group were: 14.6%, 45.2% and 33.3%, respectively. These
      measurements were significantly lower p<0.05 for the LM and MX groups in
      comparison to the M group. The number of oocytes retrieved and the number of
      embryos transferred were the lowest (p<0.001-0.05) for the LM group. It is
      concluded, that the retrieved immature oocytes are able to mature during
      overnight culture in vitro, be fertilized and provide developmentally competent
      embryos with the prognosis of 11% for the successful delivery.

PMID- 22850473
TI  - Quality and quantity of smelt (Osmerus eperlanus L.) sperm in relation to time
      after hormonal stimulation.
AB  - The effect of Ovaprim (salmon GnRH analogue and a dopamine antagonist) treatment
      on the quantity and quality of smelt (Osmerus eperlanus L.) sperm was studied in
      relation to time after hormonal stimulation. Sperm was obtained at 0, 24, 48 and
      72 h after treatment (n=13/each time point). Computer Assisted Sperm Analysis
      (CASA) was used to evaluate sperm motility parameters and histological analysis
      was used to examine the testis morphology. Only a small volume of semen (1-5 ul)
      was collected at the beginning of the experiment (time 0) but it dramatically
      increased 24 h after hormonal treatment. A further increase in semen volume was
      recorded 48 h after hormonal stimulation. CASA parameters, such as percentage of
      motile cells, progressive motility, curvilinear velocity, straightlinear
      velocity, straightness and amplitude of lateral head displacement of stripped
      sperm increased 48 h after hormonal treatment, which indicates high quality of
      sperm. No further increase in sperm quality was recorded at 72 h. Compared to
      stripped semen, testicular semen was characterized by a slightly lower quality.
      In addition, histological analysis indicated that 24 h after hormonal treatment,
      a high number of spermatozoa was released from the testis. Ovaprim-stimulated
      smelt became clearly darker than the control fish. In conclusion, our results
      suggest that smelt semen should be collected 48 h after hormonal stimulation to
      ensure high quality of semen. This time may vary depending on maturation status
      of testis.

PMID- 22850474
TI  - The ameliorative effects of Eurycoma longifolia Jack on testosterone-induced
      reproductive disorders in female rats.
AB  - The objective of this research was to study the ameliorative effects of a
      standardized quassinoid-rich extract (TAF 273) of Eurycoma longifolia root on
      some reproductive disorders in female rats. An irregular estrous cycle and
      ovarian cystic follicles were induced in 21-day-old females by the daily
      administration of testosterone (10 mg/kg, sc) for three weeks. The hormone
      treated rats exhibited persistent diestrous as well as ovaries containing cystic
      follicles. Upon treatment with TAF 273, fewer animals showed irregular estrous
      cycles and there was less follicular morphological damage. The reversal effect
      may be derived from the anti-estrogenic properties of the plant quassinoids.

PMID- 22850475
TI  - Threat bias in attention orienting: evidence of specificity in a large community
      based study.
AB  - BACKGROUND: Preliminary research implicates threat-related attention biases in
      paediatric anxiety disorders. However, major questions exist concerning
      diagnostic specificity, effects of symptom-severity levels, and threat-stimulus
      exposure durations in attention paradigms. This study examines these issues in a
      large, community school-based sample. Method A total of 2046 children (ages 6-12
      years) were assessed using the Development and Well Being Assessment (DAWBA),
      Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified
      based on presence or absence of 'fear-related' disorders, 'distress-related'
      disorders, and behavioural disorders. Two dot-probe tasks, which differed in
      stimulus exposure, assessed attention biases for happy-face and threat-face cues.
      The main analysis included 1774 children. RESULTS: For attention bias scores, a
      three-way interaction emerged among face-cue emotional valence, diagnostic group,
      and internalizing symptom severity (F = 2.87, p < 0.05). This interaction
      reflected different associations between internalizing symptom severity and
      threat-related attention bias across diagnostic groups. In children with no
      diagnosis (n = 1411, mean difference = 11.03, s.e. = 3.47, df = 1, p < 0.001) and
      those with distress-related disorders (n = 66, mean difference = 10.63, s.e. =
      5.24, df = 1, p < 0.05), high internalizing symptoms predicted vigilance towards
      threat. However, in children with fear-related disorders (n = 86, mean difference
      = -11.90, s.e. = 5.94, df = 1, p < 0.05), high internalizing symptoms predicted
      an opposite tendency, manifesting as greater bias away from threat. These
      associations did not emerge in the behaviour-disorder group (n = 211).
      CONCLUSIONS: The association between internalizing symptoms and biased orienting
      varies with the nature of developmental psychopathology. Both the form and
      severity of psychopathology moderates threat-related attention biases in
      children.

PMID- 22850476
TI  - Light level and duration of exposure determine the impact of self-luminous
      tablets on melatonin suppression.
AB  - Exposure to light from self-luminous displays may be linked to increased risk for
      sleep disorders because these devices emit optical radiation at short
      wavelengths, close to the peak sensitivity of melatonin suppression. Thirteen
      participants experienced three experimental conditions in a within-subjects
      design to investigate the impact of self-luminous tablet displays on nocturnal
      melatonin suppression: 1) tablets-only set to the highest brightness, 2) tablets
      viewed through clear-lens goggles equipped with blue light-emitting diodes that
      provided 40 lux of 470-nm light at the cornea, and 3) tablets viewed through
      orange-tinted glasses (dark control; optical radiation <525 nm ~ 0). Melatonin
      suppressions after 1-h and 2-h exposures to tablets viewed with the blue light
      were significantly greater than zero. Suppression levels after 1-h exposure to
      the tablets-only were not statistically different than zero; however, this
      difference reached significance after 2 h. Based on these results, display
      manufacturers can determine how their products will affect melatonin levels and
      use model predictions to tune the spectral power distribution of self-luminous
      devices to increase or to decrease stimulation to the circadian system.

PMID- 22850478
TI  - Ischaemic preconditioning and mitochondrial permeability transition: a long
      lasting relationship.

PMID- 22850479
TI  - New antithrombotic agents for the treatment of coronary artery disease: 
      overview.

PMID- 22850481
TI  - Bibliography-Editors' selection of current world literature.

PMID- 22850480
TI  - PAI-1 4G/5G gene polymorphism is associated with angiographic patency in ST
      elevation myocardial infarction patients treated with thrombolytic therapy.
AB  - BACKGROUND: In this study, we examined the relationship between PAI-1 4G/5G
      polymorphism and patency of the infarct-related artery after thrombolysis in
      patients with ST-elevation myocardial infarction (STEMI). METHODS: Acute STEMI
      patients who received thrombolytic therapy within first 12 h were included in our
      study. The PAI-1 4G/5G promoter region insertion/deletion polymorphism was
      studied from venous blood samples. Patients with the PAI-1 4G/5G gene
      polymorphism were included in group 1 and the others were included in group 2.
      Coronary angiography was performed in all patients in the first 24 h after
      receiving thrombolytic therapy. Thrombolysis in myocardial infarction (TIMI) 0-1
      flow in the infarct-related artery was considered as 'no flow', TIMI 2 flow as
      'slow flow', and TIMI 3 flow as 'normal flow'. RESULTS: A total of 61 patients
      were included in our study. Thirty patients (49.2%) were positive for the PAI-1
      4G/5G gene polymorphism, whereas 31 of them (50.8%) were in the control group.
      There were significantly more patients with 'no flow' (14 vs. 6; P=0.02) and less
      patients with 'normal flow' (8 vs. 19; P=0.02) in group 1. In addition, time to
      thrombolytic therapy (TTT) was maximum in the 'no flow' group and minimum in the
      'normal flow' group (P=0.005). In the logistic regression analysis, TTT (odds
      ratio: 0.9898; 95% confidence interval: 0.982-0.997; P=0.004) and the PAI-1 4G/5G
      gene polymorphism (odds ratio: 4.621; 95% confidence interval: 1.399-15.268;
      P<0.01) were found to be independently associated with post-thrombolytic 'no
      flow'. CONCLUSION: The PAI-1 4G/5G gene polymorphism and TTT are associated
      independently with 'no flow' after thrombolysis in patients with STEMI.

PMID- 22850482
TI  - New sensors for quantitative measurement of mitochondrial Zn(2+).
AB  - Zinc (Zn(2+)) homeostasis plays a vital role in cell function, and the
      dysregulation of intracellular Zn(2+) is associated with mitochondrial
      dysfunction. Few tools exist to quantitatively monitor the buffered, free Zn(2+)
      concentration in mitochondria of living cells ([Zn(2+)](mito)). We have validated
      three high dynamic range, ratiometric, genetically encoded, fluorescent Zn(2+)
      sensors that we have successfully used to precisely measure and monitor
      [Zn(2+)](mito) in several cell types. Using one of these sensors, called mito
      ZapCY1, we report observations that free Zn(2+) is buffered at concentrations
      about 3 orders of magnitude lower in mitochondria than in the cytosol and that
      HeLa cells expressing mito-ZapCY1 have an average [Zn(2+)](mito) of 0.14 pM,
      which differs significantly from other cell types. These optimized mitochondrial
      Zn(2+) sensors could improve our understanding of the relationship between Zn(2+)
      homeostasis and mitochondrial function.

PMID- 22850484
TI  - LRRK2 expression is enriched in the striosomal compartment of mouse striatum.
AB  - In spite of a clear genetic link between Parkinson's disease (PD) and mutations
      in LRRK2, cellular localization and physiological function of LRRK2 remain
      debated. Here we demonstrate the immunohistochemical localization of LRRK2 in
      adult mouse and early postnatal mouse brain development. Antibody specificity is
      verified by absence of specific staining in LRRK2 knockout mouse brain. Although
      LRRK2 is expressed in various mouse brain regions (i.e. cortex, thalamus,
      hippocampus, cerebellum), strongest expression is detected in striatum, whereas
      LRRK2 protein expression in substantia nigra pars compacta in contrast is low.
      LRRK2 is highly expressed in striatal medium spiny neurons (MSN) and few
      cholinergic interneurons. LRRK2 expression is undetectable in other interneurons,
      oligodendrocytes or astrocytes of the striatum. Interestingly, LRRK2 expression
      is associated with striosome specific markers (i.e. MOR1, RASGRP1). Analysis of
      LRRK2 expression during early postnatal development and in LRRK2 knockout mice,
      demonstrates that LRRK2 is not required for generation or maintenance of the
      striosome compartment. Comparing LRRK2-WT, LRRK2-R1441G transgenic and non
      transgenic mice, changes of LRRK2 expression in striosome/matrix compartments can
      be detected. The findings rule out a specific requirement of LRRK2 in striosome
      genesis but suggest a functional role for LRRK2 in striosomes.

PMID- 22850483
TI  - Limited regional cerebellar dysfunction induces focal dystonia in mice.
AB  - Dystonia is a complex neurological syndrome broadly characterized by involuntary
      twisting movements and abnormal postures. The anatomical distribution of the
      motor symptoms varies among dystonic patients and can range from focal, involving
      an isolated part of the body, to generalized, involving many body parts.
      Functional imaging studies of both focal and generalized dystonias in humans
      often implicate the cerebellum suggesting that similar pathological processes may
      underlie both. To test this, we exploited tools developed in mice to generate
      animals with gradients of cerebellar dysfunction. By using conditional genetics
      to regionally limit cerebellar dysfunction, we found that abnormalities
      restricted to Purkinje cells were sufficient to cause dystonia. In fact, the
      extent of cerebellar dysfunction determined the extent of abnormal movements.
      Dysfunction of the entire cerebellum caused abnormal postures of many body parts,
      resembling generalized dystonia. More limited regions of dysfunction that were
      created by electrical stimulation or conditional genetic manipulations produced
      abnormal movements in an isolated body part, resembling focal dystonia. Overall,
      these results suggest that focal and generalized dystonias may arise through
      similar mechanisms and therefore may be approached with similar therapeutic
      strategies. 

PMID- 22850485
TI  - Expression pattern and localization of alpha-synuclein in the human enteric
      nervous system.
AB  - BACKGROUND: Alpha-synuclein (alpha-syn) is abundantly expressed in the central
      nervous system and involved in the regulation of neurotransmission. Insoluble
      fibrils of phosphorylated alpha-synuclein (p-alpha-syn) have been implicated in
      several neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's
      disease). The aim of the study was to determine the gene expression pattern and
      localization of alpha-syn/p-alpha-syn in the human enteric nervous system (ENS).
      METHODS: Human colonic specimens (n=13, 15-83 years) were processed for alpha-syn
      and p-alpha-syn immunohistochemistry. Colocalization of alpha-syn was assessed by
      dual-labeling with pan-neuronal markers (PGP 9.5, HuC/D). For qPCR studies,
      tissue was obtained from full-thickness sections, tunica muscularis, submucosa,
      mucosa, and laser-microdissected (LMD) enteric ganglia. RESULTS: Highest alpha
      syn levels were detectable within the tunica muscularis and submucosa. Ganglia
      isolated by LMD showed high expression of alpha-syn mRNA. All myenteric and
      submucosal ganglia and nerve fibers were immunoreactive for alpha-syn. Dual
      labeling revealed colocalization of alpha-syn with both pan-neuronal markers. p
      alpha-syn immunoreactivity was consistently observed in specimens from adults
      with increasing age. CONCLUSIONS: alpha-syn is abundantly expressed in all nerve
      plexus of the human ENS including both neuronal somata and processes. The
      presence of p-alpha-syn within the ENS is a regular finding in adults with
      increasing age and may not be regarded as pathological correlate. The data
      provide a basis to unravel the functions of alpha-syn and to evaluate altered
      alpha-syn in enteric neuropathies and alpha-synucleinopathies of the CNS with
      gastrointestinal manifestations.

PMID- 22850486
TI  - Repetition suppression and effects of familiarity on blood oxygenation level
      dependent signal and gamma-band activity.
AB  - We used an identical repetition priming paradigm in functional MRI (fMRI) and
      magnetoencephalography (MEG) to investigate brain networks modulated by stimulus
      repetition and familiarity. In particular, pictures of familiar or unfamiliar
      objects were presented sequentially, with stimulus repetitions occurring within
      few trials. The results of both studies indicated close agreement between the
      pattern found in fMRI-BOLD (blood oxygenation level dependent) responses and in
      source localizations of induced gamma-band activity derived from MEG. In both
      studies, the brain regions that were significantly associated with repetition
      suppression in response to familiar visual objects encompassed bilaterally the
      medial and lateral occipital cortex, inferior occipitotemporal regions including
      the left fusiform cortex, as well as parietal areas. Modulations by stimulus
      familiarity occurred mainly within this network. Overall, we found noticeable
      correspondences between the results of fMRI-BOLD signals and MEG gamma-band
      activity, suggesting that both methods can be used in analogous ways to study the
      neural basis of repetition priming and object recognition.

PMID- 22850487
TI  - Orientation dependent oxygen exchange kinetics on single crystal SrTiO3 surfaces.
AB  - The perovskite SrTiO(3) is arguably one of the most important oxide systems in
      condensed matter research. In this study, we report measurement of the
      orientation dependence of oxygen exchange on SrTiO(3) single crystal surfaces by
      dynamic conductivity measurements under electrochemical perturbations. Activation
      energy for electrical conduction in the 923-1223 K range at an oxygen partial
      pressure of ~10(-11) Pa of (100), (111), and (110) single crystals was found to
      be 2.6 eV, 2.7 eV, and 3.1 eV, respectively. The equilibration kinetics show
      profound dependence on the surface orientation and are modelled using a
      heterogeneous relaxation process. All surfaces show similar cationic sub-lattice
      limited rate behavior with (111), (100), and (110) having the fastest,
      intermediate, and slowest rates, respectively. We discuss the orientation
      dependence and its relation to local atomic structure in light of previous
      experimental and theoretical studies.

PMID- 22850488
TI  - Residual complaints after neuralgic amyotrophy.
AB  - OBJECTIVE: To develop recommendations regarding outcome measures and topics to be
      addressed in rehabilitation for persons with neuralgic amyotrophy (NA), this
      study explored which functions and activities are related to persisting pain in
      NA and which questionnaires best capture these factors. DESIGN: A questionnaire
      based survey from 2 cross-sectional cohorts, one of patients visiting the
      neurology outpatient clinic and a cohort seen at a multidisciplinary plexus
      clinic. SETTING: Two tertiary referral clinics based in the Department of
      Neurology and Rehabilitation from a university medical center provided the data.
      PARTICIPANTS: A referred sample of patients (N=248) with either idiopathic or
      hereditary NA who fulfilled the criteria for this disorder, in whom the last
      episode of NA had been at least 6 months ago and included brachial plexus
      involvement. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Two custom
      clinical screening questionnaires were used as well as the Shoulder Rating
      Questionnaire-Dutch Language Version, the Shoulder Pain and Disability Index
      (SPADI), the Shoulder Disability Questionnaire (SDQ), and Overall Disability Sum
      Score. RESULTS: The survey confirms the high prevalence of persisting pain and
      impairments. More than half of the patients were restricted by pain, while in
      those without pain 60% experienced residual paresis. Correlations show an
      intimate relation between pain, scapular instability, problems with overhead
      activities, and increased fatigability. A standard physical therapy approach was
      ineffective or aggravated symptoms in more than 50%. CONCLUSIONS: Pain and
      fatigue are strongly correlated to persisting scapular instability and increased
      fatigability of the affected muscles in NA. Our results suggest that an
      integrated rehabilitation approach is needed in which all of these factors are
      addressed. We further recommend using the SPADI and SDQ in future studies to
      evaluate the natural course and treatment effects in NA.

PMID- 22850489
TI  - Effects of whole-body cryotherapy in the management of adhesive capsulitis of the
      shoulder.
AB  - OBJECTIVE: To compare 2 different treatment approaches, physical therapy
      modalities, and joint mobilization versus whole-body cryotherapy (WBC) combined
      with physical therapy modalities and joint mobilization, for symptoms of adhesive
      capsulitis (AC) of the shoulder. DESIGN: A randomized trial. SETTING: Hospital.
      PARTICIPANTS: Patients with AC of the shoulder (N=30). INTERVENTION: Patients
      were randomly assigned to 2 groups. The WBC group received physical therapy
      modalities, passive joint mobilization of the shoulder, and WBC, whereas the non
      WBC group received only physical therapy modalities and passive joint
      mobilization of the shoulder. MAIN OUTCOME MEASURES: Visual analog scale (VAS),
      active range of motion (ROM) of flexion, abduction, internal and external
      rotation of the shoulder, and the American Shoulder and Elbow Surgeons
      Standardized Shoulder Assessment Form (ASES) were measured before and after the
      intervention. RESULTS: A statistically significant difference between groups was
      found for the VAS, active ROM of flexion, abduction, internal rotation, and
      external rotation, and the ASES with greater improvements in the WBC group
      (Ps<.01). Overall, both groups showed a significant improvement in all outcome
      measures and ROM measures from pre to post at a level of P<.01. CONCLUSIONS:
      There is significant improvement with the addition of WBC to treatment
      interventions in this sample of patients.

PMID- 22850490
TI  - Helical folding in heterogeneous foldamers without inter-residual backbone
      hydrogen-bonding.
AB  - This communication describes a set of hybrid foldamers that do not feature inter
      residual, but intra-residual backbone hydrogen-bonding, yet adopt a
      preferentially folded conformation displaying right-handed helical architecture.
      Conformational ordering is apparently due to the combined conformational
      restrictions imposed by the conformationally restricted individual amino acid
      residues with which the oligomers are made of.

PMID- 22850491
TI  - Validation and the future of stimulation therapy of the primary motor cortex.
AB  - The use of electrical motor cortex stimulation (EMCS) for post-stroke pain was
      established in Japan and has spread globally. EMCS has been used for the
      treatment of neuropathic pain, Parkinson's syndrome, and recovery of motor
      paresis. Since 2000, repetitive transcranial magnetic stimulation (rTMS) has been
      developed for the treatment of various neurological disorders. rTMS is a non
      invasive method with almost no adverse effects. In the USA, rTMS of the left
      dorsolateral prefrontal cortex was approved for the treatment of major depression
      in 2008. rTMS of the primary motor cortex (M1) has been studied worldwide for the
      treatment of neuropathic pain, Parkinson's disease, motor paresis after stroke,
      and other neurological problems. New methods and devices for rTMS therapy are
      under development, and rTMS of the M1 is likely to be established as an effective
      therapy for some neurological disorders. The present review discusses EMCS and
      rTMS of the M1 concisely.

PMID- 22850492
TI  - Validation and perspectives of neuromodulation in Japan.
AB  - Neuromodulation in functional neurosurgery is closely related to the development
      and availability of devices such as implantable electric stimulators and pumps.
      All such devices used in Japan are developed and made in foreign countries, and
      no made-in-Japan device exists. Introduction and approval by the government took
      many years for most devices, during which time many patients had to continue to
      live in our medically conservative country. The history of neuromodulation is
      summarized in Japan and the problems surrounding neuromodulation pointed out.
      Everyone has to aware of such circumstances and make every effort to improve the
      internationally unusual situation of neuromodulation in Japan. Otherwise, Japan
      will become a medically isolated country in the near future.

PMID- 22850493
TI  - Neuromodulation using intrathecal baclofen therapy for spasticity and dystonia.
AB  - Intrathecal baclofen (ITB) therapy is a treatment for intractable spasticity due
      to a variety of causes. Continuous intrathecal administration of baclofen, an
      agonist of the inhibitory neurotransmitter gamma-aminobutyric acid, inhibits
      excitation of motor neurons at the spinal level and thus suppresses spasticity.
      This therapy was introduced clinically in the Europe and the United States in the
      1990s, and was finally approved by the Japanese Ministry of Health, Labour and
      Welfare in Japan in 2005. Clinical use has been permitted since 2006, and reports
      of therapeutic efficacy are now appearing in Japan. ITB therapy is a non
      destructive treatment that enables administration of baclofen from an implantable
      pump under the control of a programmer, and represents an outstanding treatment
      method offering both reversibility and adjustability. Indications for ITB therapy
      have been expanding in recent years to include not only spasticity, but also
      various causes dystonia. And ITB therapy can greatly improve activities of daily
      living and quality of life, and this treatment is attracting attention as a
      neuromodulatory therapy that also affects metabolic and respiratory functions and
      even state of consciousness. We here report the surgical methods and therapeutic
      outcomes for 22 patients who underwent ITB therapy for spastic and dystonic
      patients in our hospital, together with an investigation of the effects on
      metabolic and respiratory functions.

PMID- 22850494
TI  - Spinal cord stimulation for the treatment of abnormal posture and gait disorder
      in patients with Parkinson's disease.
AB  - Patients with advanced Parkinson's disease (PD) often present with axial
      symptoms, including abnormal posture, postural instability, and gait disorder.
      Although spinal cord stimulation (SCS) is effective for pain, little is known
      about the effect of SCS on motor function in PD patients. The present study
      investigated the effect of SCS on posture and gait in 15 PD patients, 5 men and
      10 women aged 63-79 years (mean 71.1 years), with low back pain and leg pain who
      received SCS. A visual analog scale (VAS) was used for pain evaluation pre- and
      postoperatively. The Unified Parkinson's Disease Rating Scale, Timed Up and Go
      tests, and Timed 10-Meter Walk tests were used to evaluate motor function and
      activities of daily living of patients. Preoperative mean VAS score was 8.9
      (range 7.8-10), which showed significant postoperative improvement at 3 months to
      mean VAS score of 2.0 (range 0-3.3). The improvements in VAS scores persisted at
      12 months after surgery with mean VAS score of 2.3 (range 0-4). Posture and
      postural stability motor subscores were improved at 3 months after SCS, and gait
      had significantly improved at 3 months and 1 year after surgery. Timed 10-Meter
      Walk tests also demonstrated that patient gait was significantly improved at 3
      months and 12 months after surgery. Most advanced stage PD patients suffer
      considerable pain that causes abnormal posture and gait disturbance. SCS is
      expected to lead to both amelioration of pain and improvement of motor function
      in such patients.

PMID- 22850495
TI  - Spinal cord stimulation for treatment of patients in the minimally conscious
      state.
AB  - Minimally conscious state (MCS) is characterized by inconsistent but clearly
      discernible behavioral evidence of consciousness, and can be distinguished from
      coma and the vegetative state (VS). Ten MCS patients were evaluated
      neurologically and electrophysiologically over 3 months after the onset of brain
      injury, and were treated by spinal cord stimulation (SCS). A flexible four
      contact, cylinder electrode was inserted into the epidural space of the cervical
      vertebrae, and placed at the C2-C4 levels. Stimulation was applied for 5 minutes
      every 30 minutes during the daytime at an intensity that produced motor twitches
      of the upper extremities. We used 5 Hz for SCS, considering that the induced
      muscle twitches can be a useful functional neurorehabilitation for MCS patients.
      Eight of the 10 MCS patients satisfied the electrophysiological inclusion
      criteria, which we proposed on the basis of the results of deep brain stimulation
      for the treatment of patients in the VS. Seven patients recovered from MCS
      following SCS therapy, and were able to carry out functional interactive
      communication and/or demonstrate the functional use of two different objects.
      Cervical SCS increased cerebral blood flow (CBF) diffusely in the brain, and CBF
      increased by 22.2% during the stimulation period compared with CBF before
      stimulation in MCS patients (p < 0.0001, paired t-test). Five-Hz cervical SCS
      could increase CBF and induce muscle twitches of the upper extremities. This SCS
      therapy method may be suitable for treating MCS.

PMID- 22850496
TI  - Cost-effectiveness analysis of intrathecal baclofen therapy in Japan.
AB  - Intrathecal baclofen (ITB) therapy was approved for health insurance coverage in
      2005 for the treatment of patients whose spasticity could not be adequately
      controlled by conventional therapy, and is currently being used to treat around
      300 patients nationwide in Japan. Various reports have examined the efficacy and
      safety of ITB therapy, but no report has evaluated the patient quality of life
      and medical costs in Japan. A cost-utility analysis of ITB was conducted by time
      period in six severely spastic patients admitted to our university hospital
      between 2005 and 2010 for ITB therapy. The average cost of ITB therapy per
      quality-adjusted life year (QALY; number of years survival in perfect health) 5
      years after surgery was 1,554,428 yen, below the 6 million yen willingness-to-pay
      threshold for 1 QALY. This study shows that ITB therapy in Japan is an
      outstanding treatment in medicoeconomic terms.

PMID- 22850497
TI  - Early cerebral circulatory disturbance in patients suffering subarachnoid
      hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed
      tomography and perfusion computed tomography study.
AB  - Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow
      (CBF), and results in delayed ischemia due to vasospasm, and early perfusion
      deficits before delayed cerebral vasospasm (CVS). The present study examined the
      severity of cerebral circulatory disturbance during the early phase before
      delayed CVS and whether it can be used to predict patient outcome. A total of 94
      patients with SAH underwent simultaneous xenon computed tomography (CT) and
      perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow
      (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion
      CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the
      Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe
      disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade
      II patients displayed significantly higher CBF and lower MTT than HH grade IV and
      V patients. HH grade III patients displayed significantly higher CBF and lower
      MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD)
      had significantly higher CBF and lower MTT than those with unfavorable outcome
      (SD, VS, or D). Discriminant analysis of these parameters could predict patient
      outcome with a probability of 74.5%. Higher HH grade on admission was associated
      with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation
      before the onset of delayed CVS might influence the clinical outcome of SAH.
      These parameters are helpful for evaluating the severity of SAH and predicting
      the outcomes of SAH patients.

PMID- 22850498
TI  - Subarachnoid hemorrhage caused by ruptured intracranial fusiform aneurysm
      associated with microscopic polyangiitis.
AB  - A 44-year-old woman with microscopic polyangiitis (MPA) presented with a ruptured
      cerebral aneurysm. She was admitted to our hospital for further examination of
      progressive renal failure. She was found lying on the ward floor. Computed
      tomography showed subarachnoid hemorrhage, and digital subtraction angiography
      revealed a saccular-like aneurysm arising from the right distal posterior
      inferior cerebellar artery (PICA) at the non-branching site. We performed neck
      clipping of the right distal PICA aneurysm, which recurred 5 days after the
      operation. Second angiography demonstrated a right distal PICA aneurysm just
      above the site of the clip. Therefore, we performed trapping of the affected
      lesion with emergent bypass of the contralateral occipital artery to the
      ipsilateral PICA. Her postoperative course was uneventful until she coughed up
      blood and had gross hematuria 3 days after the second surgery. Histological
      examination of a renal biopsy specimen revealed crescentic glomerulonephritis.
      MPA was diagnosed on the basis of the cardinal symptoms, including progressive
      glomerular nephritis and the lung abnormality, as well as the presence of
      myeloperoxidase-antineutrophil cytoplasmic antibodies. After intensive treatment,
      she was discharged for rehabilitation without neurological deficit. MPA commonly
      affects small-sized vessels mainly in the kidneys and lungs and may lead to
      crescentic glomerulonephritis and pulmonary hemorrhage. MPA is rarely associated
      with aneurysms of medium-sized muscular vessels. Cerebral aneurysm is extremely
      rare in patients with MPA, but rupture of an intracranial fusiform aneurysm can
      be lethal, so screening of the intracranial vessels should be performed by
      magnetic resonance imaging in patients with MPA.

PMID- 22850499
TI  - Subarachnoid hemorrhage caused by ruptured posterior inferior cerebellar artery
      aneurysm arising from the extracranial portion of an anomalous vertebral artery.
AB  - A 42-year-old woman presented with subarachnoid hemorrhage caused by a ruptured
      posterior inferior cerebellar artery aneurysm arising from the extracranial
      portion of an anomalous vertebral artery. We speculated that the aneurysm formed
      by dissection of the media because of its shape and location. Therefore, the
      aneurysm was isolated by trapping and excised, with occipital artery to posterior
      inferior cerebellar artery bypass. Histological examination showed a typical true
      aneurysm without evidence of dissection. This case suggests that an aneurysm of
      an anomalous artery is caused by hemodynamic stress and is a true aneurysm, not a
      dissection.

PMID- 22850500
TI  - Ruptured large basilar artery aneurysm associated with an arteriovenous
      malformation in hereditary hemorrhagic telangiectasia.
AB  - A 53-year-old woman presented with intracranial hemorrhage caused by a ruptured
      cerebral aneurysm. Digital subtraction angiography revealed a large aneurysm
      arising from the top of the basilar artery and a Spetzler-Martin grade 3
      arteriovenous malformation. Endovascular embolization of the aneurysm was
      completed with a slight neck remnant. Medical examination confirmed that she
      suffered from hereditary hemorrhagic telangiectasia (HHT). HHT is a rare
      autosomal dominant disorder characterized by multiple mucocutaneous
      telangiectasia and associated vascular malformations. This case suggests that the
      prognosis for HHT patients with treatable aneurysms should be as good as that of
      healthy individuals. Consequently, neurosurgeons should suspect underlying HHT in
      all patients with cerebral vascular malformations.

PMID- 22850501
TI  - Giant calcified thrombosed varices secondary to a pial arteriovenous fistula
      associated with hereditary hemorrhagic telangiectasia.
AB  - A 28-year-old woman presented with an unusual case of giant thrombosed varix with
      calcified walls that had mass effects secondary to a pial single-channel
      arteriovenous fistula (AVF) associated with hereditary hemorrhagic telangiectasia
      (HHT). She consulted our hospital for chronic headache. She had been diagnosed
      with HHT based on genetic testing when her 3-year-old son presented with
      subarachnoid hemorrhage due to spinal AVF. Imaging studies revealed pial single
      channel AVF with multiple varices. The varices in the right frontal lobe were
      over 6 cm in diameter and had laminar thromboses and calcified walls. Because of
      the mass effect, direct surgical flow disconnection was performed followed by
      removal of the varices using an internal decompression technique.
      Postoperatively, the patient was discharged with no neurological symptoms and no
      longer suffered chronic headache. Intracerebral varices are occasionally
      associated with high-flow AVF, and usually treated by interrupting the feeding
      arteries leaving the varices intact. This extremely rare case of intracerebral
      giant thrombosed varices with calcified wall and mass effect indicates that
      surgical removal of varices should be considered.

PMID- 22850502
TI  - Paravertebral arteriovenous fistula treated by endovascular coil embolization.
AB  - A 41-year-old man, without underlying health problems or traumatic episodes,
      presented with a rare paravertebral arteriovenous fistula (AVF) causing
      radiculopathy manifesting as gradually progressive right grip weakness, and right
      thumb, index, and middle finger numbness. Digital subtraction angiography
      revealed a high flow, single hole paravertebral AVF fed by the right
      thyrocervical trunk that drained into the epidural venous plexus. The patient
      underwent endovascular embolization of the AVF via the transarterial approach.
      The fistula was completely occluded by coil embolization. Postembolization,
      clinical symptoms improved and 6-month follow-up angiography showed no recurrence
      of the fistula. Paravertebral AVF is a rare vascular malformation occurring
      outside the dura mater, fed by dural or epidural branches, and draining primarily
      into the epidural venous plexus. Paravertebral AVF is usually asymptomatic
      because of a "reflux-impending mechanism" within the dural sleeves that prevents
      retrograde drainage into the perimedullary veins. However, in the present case,
      mechanical compression of the radicular nerve due to a dilated epidural venous
      plexus resulted in neurological symptoms. We conclude that endovascular surgery
      is an effective treatment strategy for paravertebral AVF.

PMID- 22850503
TI  - Rare variant of persistent primitive hypoglossal artery, arising from the
      external carotid artery.
AB  - A 63-year-old man presented with an extremely rare variant of persistent
      primitive hypoglossal artery (PHA), which was found incidentally during
      examination for a contralateral asymptomatic internal carotid artery (ICA)
      stenosis. This anastomotic vessel arose from the external carotid artery, not the
      ICA, and joined the vertebrobasilar artery through the hypoglossal canal.
      Persistent PHA is rare and the reported incidence is 0.027-0.26%. Recognition of
      the existence of this variant vessel and preservation during neuroradiologic
      intervention or surgery is important to prevent possible ischemic complications.

PMID- 22850504
TI  - Deterioration after surgical treatment of spinal dural arteriovenous fistula
      associated with spinal perimedullary fistula.
AB  - Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of vascular
      malformations of the spine and are defined as abnormal arteriovenous shunts
      within the dura. SDAVFs are considered to be acquired and should be distinguished
      from congenital intradural perimedullary arteriovenous fistulas (PMAVFs). A 32
      year-old female presented with both SDAVF and PMAVF, manifesting as a slowly
      progressive paraparesis over a 6-month period. Initial spinal angiography
      demonstrated an SDAVF in the sacral region and was terminated with incomplete
      demonstration of all segmental arteries. The fistula was obliterated by surgery
      and the patient showed transient postoperative improvement followed by delayed
      deterioration 2 months later. Magnetic resonance (MR) imaging showed many
      hypointense flow voids around the cord. The second angiography verified a PMAVF
      in the lumbar region and complete obliteration of the SDAVF. The fistula was
      closed by surgery and the patient improved slightly. Surgical results of SDAVFs
      are generally good. Therefore, if a patient fails to improve or deteriorates
      further after surgery with persistent perimedullary vessel abnormalities on MR
      imaging, the possibility of reopening of the fistula or the presence of another
      fistula should be considered and repeat angiography must be performed, especially
      if the initial angiography was incomplete.

PMID- 22850505
TI  - Watertight dural closure constructed with DuraSeal TM for bypass surgery.
AB  - Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is a
      common procedure for the treatment of cerebral ischemia and is useful for
      cerebral aneurysms and tumors. The STA has to pass through the dura and the dura
      cannot be sutured tightly around the STA to prevent vessel narrowing, so
      subcutaneous cerebrospinal fluid (CSF) collection is common. This study analyzed
      the feasibility of using a synthetic dural sealant in the STA-MCA anastomosis to
      establish watertight closure. Twenty-four patients underwent STA-MCA anastomosis
      for cerebral ischemia or cerebral aneurysm. After creation of a standard STA-MCA
      anastomosis, the dura was reapproximated closely, leaving a small defect around
      the STA. Then, DuraSeal(TM) was sprayed over the dural defect, and a negative
      pressure drain was positioned before closing the skin. Only two patients
      developed subcutaneous CSF collection, which was managed conservatively. The
      patency of the anastomosis was proven by magnetic resonance angiography in all
      cases, and no ischemic complication suggesting chemical spasm of the STA due to
      the sealant occurred. With DuraSeal(TM), watertight dural closure can be obtained
      easily and safely in bypass surgery.

PMID- 22850506
TI  - Direct-puncture embolization of scalp arteriovenous fistulae.
AB  - We present our experience of flow control with the aid of a circular compression
      device (CCD) for embolization of scalp arteriovenous fistulae (sAVFs). A 21-year
      old female presented with a pulsating scalp mass with sAVFs fed by the
      superficial temporal arteries. A CCD with a beveled circular handle and
      concentric hole was used to treat the condition. After the CCD was compressed
      over the area of the fistulae, the fistulae were punctured and blood
      regurgitation was assured. While maintaining flow stasis within the boundary of
      the CCD and loading heparinized dextrose-saline solution, a 50% mixture of N
      butyl-2-cyanoacrylate and Lipiodol was applied during the compression, which was
      sustained for 1-2 minutes. Finally, the sAVFs were almost completely occluded
      without complications. Our designed CCD was effective for flow control, and
      direct-puncture embolization of N-butyl-2-cyanoacrylate during flow control using
      the CCD was safe and effective for the treatment of sAVFs.

PMID- 22850507
TI  - A mutation in the PP2C phosphatase gene in a Staphylococcus aureus USA300
      clinical isolate with reduced susceptibility to vancomycin and daptomycin.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced
      susceptibility to vancomycin (MIC of 4 to 8 MUg/ml) are referred to as vancomycin
      intermediate S. aureus (VISA). In this study, we characterized two isogenic
      USA300 S. aureus isolates collected sequentially from a single patient with
      endocarditis where the S. aureus isolate changed from being susceptible to
      vancomycin (VSSA) (1 MUg/ml) to VISA (8 MUg/ml). In addition, the VISA isolate
      lost beta-lactamase activity and showed increased resistance to daptomycin and
      linezolid. The two strains did not differ in growth rate, but the VISA isolate
      had a thickened cell wall and was less autolytic. Transcriptome sequencing (RNA
      seq) analysis comparing the two isolates grown to late exponential phase showed
      significant differences in transcription of cell surface protein genes (spa, SBI
      [second immunoglobulin-binding protein of S. aureus], and fibrinogen-binding
      proteins), regulatory genes (agrBCA, RNAIII, sarT, and saeRS), and others. Using
      whole-genome shotgun resequencing, we identified 6 insertion/deletion mutations
      between the VSSA and VISA isolates. A protein phosphatase 2C (PP2C) family
      phosphatase had a 6-bp (nonframeshift) insertion mutation in a highly conserved
      metal binding domain. Complementation of the clinical VISA isolate with a wild
      type copy of the PP2C gene reduced the vancomycin and daptomycin MICs and
      increased autolytic activity, suggesting that this gene contributed to the
      reduced vancomycin susceptibility phenotype acquired in vivo. Creation of de novo
      mutants from the VSSA strain resulted in different mutations, demonstrating that
      reduced susceptibility to vancomycin in USA300 strains can occur via multiple
      routes, highlighting the complex nature of the VISA phenotype.

PMID- 22850509
TI  - Linezolid is superior to vancomycin in experimental pneumonia caused by
      Superantigen-Producing staphylococcus aureus in HLA class II transgenic mice.
AB  - Superantigens (SAg), the potent activators of the immune system, are important
      determinants of Staphylococcus aureus virulence and pathogenicity. Superior
      response to SAg in human leukocyte antigen (HLA)-DR3 transgenic mice rendered
      them more susceptible than C57BL/6 mice to pneumonia caused by SAg-producing
      strains of S. aureus. Linezolid, a bacterial protein synthesis inhibitor, was
      superior to vancomycin in inhibiting SAg production by S. aureus in vitro and
      conferred greater protection from pneumonia caused by SAg-producing
      staphylococci.

PMID- 22850510
TI  - Cobicistat boosts the intestinal absorption of transport substrates, including
      HIV protease inhibitors and GS-7340, in vitro.
AB  - The experimental pharmacoenhancer cobicistat (COBI), a potent mechanism-based
      inhibitor of cytochrome P450 3A enzymes, was found to inhibit the intestinal
      efflux transporters P-glycoprotein and breast cancer resistance protein.
      Consistent with its transporter inhibition, COBI significantly increased the
      absorptive flux of potential candidates for clinical coadministration, including
      the HIV protease inhibitors atazanavir and darunavir and the lymphoid cell- and
      tissue-targeted prodrug of the nucleotide analog tenofovir, GS-7340, through
      monolayers of Caco-2 cells in vitro.

PMID- 22850508
TI  - Identification of small molecules that antagonize diguanylate cyclase enzymes to
      inhibit biofilm formation.
AB  - Bacterial biofilm formation is responsible for numerous chronic infections,
      causing a severe health burden. Many of these infections cannot be resolved, as
      bacteria in biofilms are resistant to the host's immune defenses and antibiotic
      therapy. New strategies to treat biofilm-based infections are critically needed.
      Cyclic di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential
      for biofilm formation. As this signaling system is found only in bacteria, it is
      an attractive target for the development of new antibiofilm interventions. Here,
      we describe the results of a high-throughput screen to identify small-molecule
      inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c-di-GMP. We
      report seven small molecules that antagonize these enzymes and inhibit biofilm
      formation by Vibrio cholerae. Moreover, two of these compounds significantly
      reduce the total concentration of c-di-GMP in V. cholerae, one of which also
      inhibits biofilm formation by Pseudomonas aeruginosa in a continuous-flow system.
      These molecules represent the first compounds described that are able to inhibit
      DGC activity to prevent biofilm formation.

PMID- 22850511
TI  - Evaluation of an oral suspension of VP20621, spores of nontoxigenic Clostridium
      difficile strain M3, in healthy subjects.
AB  - VP20621, spores of nontoxigenic Clostridium difficile (NTCD) strain M3, is
      protective against challenge with toxigenic strains in hamsters. Human
      administration and colonization may prevent primary C. difficile infection (CDI)
      or recurrent CDI. Healthy adult subjects 18 to 45 years old or >=60 years old
      received single or multiple doses of an oral suspension of VP20621 (10(4), 10(6),
      or 10(8) spores) or placebo. Group 4 (>=60 years old) received oral vancomycin
      for 5 days, followed by 14 days of VP20621 or placebo. Subjects were monitored
      for safety and followed through day 28. Stool was cultured for C. difficile
      before, during, and after VP20621 administration. Isolates were tested for toxin
      by enzyme immunoassay, and VP20621 was confirmed by molecular typing. After
      single escalating doses, no subjects had C. difficile-positive stool cultures.
      VP20621 was found in the stool of all subjects given 10(8) spores twice a day.
      Following vancomycin administration, VP20621 was detected in the stool of all
      subjects given 10(4), 10(6), or 10(8) spores daily beginning on day 2 to 6.
      Recovered isolates were toxin negative and confirmed to be VP20621. There were no
      serious adverse events, and no subjects prematurely discontinued study drugs.
      Following vancomycin administration, 2 placebo subjects became colonized with
      toxigenic C. difficile and 3 placebo subjects became colonized with VP20621.
      Persistent colonization with VP20621 was detected in stools on days 21 to 28 in
      44% of subjects. VP20621 was well tolerated and able to colonize the
      gastrointestinal tracts of subjects pretreated with vancomycin. Further study of
      VP20621 to prevent CDI in patients is warranted.

PMID- 22850512
TI  - Consequences of delayed ciprofloxacin and doxycycline treatment regimens against
      Francisella tularensis airway infection.
AB  - This study examines the efficacy, bacterial load, and humoral response of
      extensively delayed ciprofloxacin or doxycycline treatments following airway
      exposure of mice to Francisella tularensis subsp. holarctica (strain LVS) or to
      the highly virulent F. tularensis subsp. tularensis (strain SchuS4). A delay in
      onset of both antibiotic treatments allowed the rescue of all LVS-infected
      animals. However, for animals infected with SchuS4, only ciprofloxacin was
      efficacious and prolongation of treatment rescued all animals.

PMID- 22850513
TI  - Effect on hepatitis C virus replication of combinations of direct-acting
      antivirals, including NS5A inhibitor daclatasvir.
AB  - Three hepatitis C virus (HCV) inhibitors, asunaprevir (ASV; BMS-650032),
      daclatasvir (DCV; BMS-790052), and BMS-791325, each targeting a different
      nonstructural protein of the virus (NS3, NS5A, and NS5B, respectively), have
      independently demonstrated encouraging preclinical profiles and are currently
      undergoing clinical evaluation. Since drug-resistant variants have rapidly
      developed in response to monotherapy with almost all direct-acting antiviral
      agents (DAAs) for HCV, the need for combination therapies to effectively
      eradicate the virus from infected patients is clear. These studies demonstrated
      the additive-synergistic effects on replicon inhibition and clearance of
      combining NS3 protease or NS5B RNA polymerase inhibitors with the first-in-class,
      NS5A replication complex inhibitor daclatasvir (DCV) and reveal new resistance
      pathways for combinations of two small-molecule inhibitors that differ from those
      that develop during monotherapy. The results suggest that under a specific
      selective pressure, a balance must be reached in the fitness costs of
      substitutions in one target gene when substitutions are also present in another
      target gene. Further synergies and additional novel resistance substitutions were
      observed during triple-combination treatment relative to dual-drug therapy,
      indicating that, in combination, HCV inhibitors can exert cross-target influences
      on resistance development. Enhanced synergies in replicon inhibition and a
      reduced frequency of resistance together lend strong support to the utility of
      combinations of DAAs for the treatment of HCV, and the identification of altered
      resistance profiles during combination treatment provides useful information for
      monitoring resistance in the clinic.

PMID- 22850514
TI  - Effect of systemic infection induced by Pseudomonas aeruginosa on the brain
      uptake of colistin in mice.
AB  - In view of reports of colistin-induced neurotoxicity in infected patients, the
      aim of this study was to assess whether the integrity of the blood-brain barrier
      (BBB) and the brain uptake of colistin are altered in the presence of systemic
      Pseudomonas aeruginosa infection. Bacteremia was confirmed 8 h after
      intramuscular administration of P. aeruginosa ATCC 27853 to Swiss Outbred mice,
      at which time a single subcutaneous dose of colistin sulfate (40 mg/kg of body
      weight) or an intravenous dose of [(14)C]sucrose (2 MUCi) was administered.
      Despite a substantial elevation in plasma levels of the proinflammatory cytokines
      tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 during
      bacterial infection, the brain uptake of colistin was similar between infected
      and noninfected mice with AUC(brain)/AUC(plasma) (where AUC(brain) is the area
      under the brain concentration-time curve and AUC(plasma) is the area under the
      plasma concentration-time curve) ratios of 0.023 and 0.024, respectively.
      Similarly, the brain-to-plasma ratios of [(14)C]sucrose were no different between
      infected and noninfected mice, consistent with a lack of effect of bacteremia on
      BBB integrity. To further correlate any relationship between BBB disruption and
      plasma levels of proinflammatory cytokines, BBB integrity, colistin brain uptake,
      and plasma proinflammatory cytokines were measured following the administration
      of Salmonella enterica lipopolysaccharide (LPS), an agent known to induce BBB
      disruption. Despite LPS inducing a 4-fold increase in colistin brain uptake and a
      significant (P < 0.05) 1.2-fold increase in [(14)C]sucrose BBB penetration,
      plasma cytokine levels were lower with LPS treatment relative to those obtained
      with bacterial infection with P. aeruginosa. This study demonstrates that the
      brain uptake of colistin is not increased in mice during P. aeruginosa-induced
      systemic bacteremia despite a significant increase in plasma levels of three
      proinflammatory cytokines.

PMID- 22850515
TI  - Therapeutic drug monitoring of posaconazole in allogeneic hematopoietic stem cell
      transplantation patients who develop gastrointestinal graft-versus-host disease.
AB  - Posaconazole (PCZ) is the latest triazole antifungal agent that has been approved
      for prophylaxis of invasive aspergillosis in high-risk immunocompromised
      patients, such as allogeneic hematopoietic stem cell transplantation patients,
      who develop graft-versus-host disease (GVHD). PCZ has high interindividual
      variability with regard to its plasma drug trough concentrations (C(min)).
      Moreover, the concentration-efficiency relationship remains to be better
      characterized in prophylaxis. To determine the variability factors in plasma drug
      concentrations, the PCZ C(min) and clinical parameters (localization of GVHD,
      presence of diarrhea, and diagnosis of invasive aspergillosis) were collected
      retrospectively in 29 consecutive allogeneic hematopoietic stem cell
      transplantation patients who developed GVHD and were receiving prophylactic PCZ
      (200 mg, 3 times/day, for >=7 days). Blood samples were analyzed at steady state
      to determine the PCZ C(min) by liquid chromatography-tandem mass spectrometry.
      The average PCZ C(min) was 1.28 +/- 0.82 mg/liter (mean +/- standard deviation; n
      = 292 dosages), with an intraindividual variability of 49% and an interindividual
      variability of 64%. Twenty percent of C(min)s were below 0.7 mg/liter, which is
      considered the threshold of efficacy by the Food and Drug Administration. The
      patients who had gastrointestinal (GI) GVHD experienced a 24% reduction in the
      posaconazole C(min), compared with those with other localizations of GVHD. This
      decrease reached 33% when patients presented with diarrhea due to GI GVHD or an
      infectious etiology. PCZ C(min)s were 26% lower when invasive aspergillosis was
      declared. These data demonstrate that GI disturbances affect drug concentrations.
      Thus, therapeutic monitoring of PCZ can be used to detect low drug
      concentrations, possibly resulting in a lack of efficacy of invasive
      aspergillosis prophylaxis.

PMID- 22850516
TI  - Comparative pharmacokinetics of continuous and conventional intrathecal
      amphotericin B in rabbits.
AB  - We previously reported a new effective therapy, continuous intrathecal
      amphotericin B (AMB), for the treatment of cryptococcal meningitis, which had
      fewer side effects and complications than conventional intrathecal AMB. In this
      study, the pharmacokinetics of continuous intrathecal administration and
      conventional intrathecal AMB were compared in rabbits, providing a
      pharmacokinetic basis for the use of continuous intrathecal AMB therapy. The AMB
      concentration in the cerebrospinal fluid (CSF), sampled via an inserted cisterna
      magna catheter, was determined by a liquid chromatography-tandem mass
      spectrometry assay. The results revealed significant pharmacokinetic differences
      between the two groups. In the continuous intrathecal group (0.15 mg/kg/24 h),
      the concentration of AMB peaked 7.01 MUg/ml at 4 h and then decreased to a stable
      level of 1.0 to 1.34 MUg/ml, with no neurological impairments, while in the
      conventional intrathecal group (0.015 mg/kg), the drug concentration reached a
      peak of 3.41 MUg/ml at 1 h and then decreased progressively, with fever and
      neurological impairments, including convulsion and paralysis. The pharmacokinetic
      results indicated that the continuous intrathecal AMB is a more effective and
      safe therapy than the conventional intrathecal AMB, with comparatively rational
      pharmacokinetics and fewer neurological impairments.

PMID- 22850517
TI  - Pharmacokinetics of amphotericin B colloidal dispersion in critically ill
      patients with cholestatic liver disease.
AB  - The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was
      assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and
      in 9 subjects with normal liver function treated with AMB colloidal dispersion
      (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of
      liberated AMB were elevated by CSLD only after the first dose, whereas its
      pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is
      probably adequate for patients with CSLD.

PMID- 22850518
TI  - Chemical inhibitors of the type three secretion system: disarming bacterial
      pathogens.
AB  - The recent and dramatic rise of antibiotic resistance among bacterial pathogens
      underlies the fear that standard treatments for infectious disease will soon be
      largely ineffective. Resistance has evolved against nearly every clinically used
      antibiotic, and in the near future, we may be hard-pressed to treat bacterial
      infections previously conquered by "magic bullet" drugs. While traditional
      antibiotics kill or slow bacterial growth, an important emerging strategy to
      combat pathogens seeks to block the ability of bacteria to harm the host by
      inhibiting bacterial virulence factors. One such virulence factor, the type three
      secretion system (T3SS), is found in over two dozen Gram-negative pathogens and
      functions by injecting effector proteins directly into the cytosol of host cells.
      Without T3SSs, many pathogenic bacteria are unable to cause disease, making the
      T3SS an attractive target for novel antimicrobial drugs. Interdisciplinary
      efforts between chemists and microbiologists have yielded several T3SS
      inhibitors, including the relatively well-studied salicylidene acylhydrazides.
      This review highlights the discovery and characterization of T3SS inhibitors in
      the primary literature over the past 10 years and discusses the future of these
      drugs as both research tools and a new class of therapeutic agents.

PMID- 22850519
TI  - Various pfcrt and pfmdr1 genotypes of Plasmodium falciparum cocirculate with P.
      malariae, P. ovale spp., and P. vivax in northern Angola.
AB  - Artemisinin-based combination therapy for malaria has become widely available
      across Africa. Populations of Plasmodium falciparum that were previously
      dominated by chloroquine (CQ)-resistant genotypes are now under different drug
      selection pressures. P. malariae, P. ovale curtisi, and P. ovale wallikeri are
      sympatric with P. falciparum across the continent and are frequently present as
      coinfections. The prevalence of human Plasmodium species was determined by PCR
      using DNA from blood spots collected during a cross-sectional survey in northern
      Angola. P. falciparum was genotyped at resistance-associated loci in pfcrt and
      pfmdr1 by real-time PCR or by direct sequencing of amplicons. Of the 3,316
      samples collected, 541 (16.3%) contained Plasmodium species infections; 477
      (88.2%) of these were P. falciparum alone, 6.5% were P. falciparum and P.
      malariae together, and 1.1% were P. vivax alone. The majority of the remainder
      (3.7%) harbored P. ovale curtisi or P. ovale wallikeri alone or in combination
      with other species. Of 430 P. falciparum isolates genotyped for pfcrt, 61.6%
      carried the wild-type allele CVMNK at codons 72 to 76, either alone or in
      combination with the resistant allele CVIET. No other pfcrt allele was found.
      Wild-type alleles dominated at codons 86, 184, 1034, 1042, and 1246 of the pfmdr1
      locus among the sequenced isolates. In contrast to previous studies, P.
      falciparum in the study area comprises an approximately equal mix of genotypes
      associated with CQ sensitivity and with CQ resistance, suggesting either lower
      drug pressure due to poor access to treatment in rural areas or a rapid impact of
      the policy change away from the use of standard monotherapies.

PMID- 22850520
TI  - In vitro activity of fluorescent dyes against asexual blood stages of Plasmodium
      falciparum.
AB  - Many successful antimicrobial drugs originate from synthetic dyes. This paper
      reports the in vitro activity of 14 fluorescent dyes against Plasmodium
      falciparum. Five of these dyes (Hoechst 33342, MitoRed, DiOC(6), SYTO 9, and
      rhodamine B) show activity at a low nanomolar concentration against two P.
      falciparum strains in the histidine-rich protein 2 drug sensitivity assay, while
      toxicity in HeLa cells is low. These dyes may be a starting point for developing
      new drugs against P. falciparum.

PMID- 22850521
TI  - Indotecan (LMP400) and AM13-55: two novel indenoisoquinolines show potential for
      treating visceral leishmaniasis.
AB  - Visceral leishmaniasis is an emerging neglected tropical disease (NTD) caused by
      the protozoan Leishmania infantum in the countries bordering the Mediterranean
      Basin. Currently there is no effective vaccine against this disease, and the
      therapeutic approach is based on toxic derivatives of Sb(V). Therefore, the
      discovery of new therapeutic targets and the development of drugs designed to
      inhibit them comprise an extremely important approach to fighting this disease.
      DNA topoisomerases (Top) have been identified as promising targets for therapy
      against leishmaniasis. These enzymes are involved in solving topological problems
      generated during replication, transcription, and recombination of DNA. Being
      unlike that of the mammalian host, type IB DNA topoisomerase (TopIB) from
      Leishmania spp. is a unique bisubunit protein, which makes it very interesting as
      a selective drug target. In the present investigation, we studied the effect of
      two TopIB poisons with indenoisoquinoline structure, indotecan and AM13-55, on a
      murine BALB/c model of infected splenocytes with L. infantum, comparing their
      effectiveness with that of the clinically tested leishmanicidal drug paromomycin.
      Both compounds have high selectivity indexes compared with uninfected
      splenocytes. SDS-KCl-precipitable DNA-protein complexes in Leishmania
      promastigotes and in vitro cleaving assays confirmed that these drugs are Top
      poisons. The inhibitory potency of both indenoisoquinolines on L. infantum
      recombinant TopIB was assessed in vitro, with results showing that indotecan was
      the most active compound, preventing the relaxation of supercoiled DNA.
      Experimental infections in susceptible BALB/c mice treated with 2.5 mg/kg body
      weight/day once every other day for a total of 15 days showed that indotecan
      cleared more than 80% of the parasite burden of the spleen and liver, indicating
      promising activity against visceral leishmaniasis.

PMID- 22850522
TI  - Comparative ex vivo activity of novel endoperoxides in multidrug-resistant
      plasmodium falciparum and P. vivax.
AB  - The declining efficacy of artemisinin derivatives against Plasmodium falciparum
      highlights the urgent need to identify alternative highly potent compounds for
      the treatment of malaria. In Papua Indonesia, where multidrug resistance has been
      documented against both P. falciparum and P. vivax malaria, comparative ex vivo
      antimalarial activity against Plasmodium isolates was assessed for the
      artemisinin derivatives artesunate (AS) and dihydroartemisinin (DHA), the
      synthetic peroxides OZ277 and OZ439, the semisynthetic 10-alkylaminoartemisinin
      derivatives artemisone and artemiside, and the conventional antimalarial drugs
      chloroquine (CQ), amodiaquine (AQ), and piperaquine (PIP). Ex vivo drug
      susceptibility was assessed in 46 field isolates (25 P. falciparum and 21 P.
      vivax). The novel endoperoxide compounds exhibited potent ex vivo activity
      against both species, but significant differences in intrinsic activity were
      observed. Compared to AS and its active metabolite DHA, all the novel compounds
      showed lower or equal 50% inhibitory concentrations (IC(50)s) in both species
      (median IC(50)s between 1.9 and 3.6 nM in P. falciparum and 0.7 and 4.6 nM in P.
      vivax). The antiplasmodial activity of novel endoperoxides showed different cross
      susceptibility patterns in the two Plasmodium species: whereas their ex vivo
      activity correlated positively with CQ, PIP, AS, and DHA in P. falciparum, the
      same was not apparent in P. vivax. The current study demonstrates for the first
      time potent activity of novel endoperoxides against drug-resistant P. vivax. The
      high activity against drug-resistant strains of both Plasmodium species confirms
      these compounds to be promising candidates for future artemisinin-based
      combination therapy (ACT) regimens in regions of coendemicity.

PMID- 22850523
TI  - Intracellular toxicity of proline-rich antimicrobial peptides shuttled into
      mammalian cells by the cell-penetrating peptide penetratin.
AB  - The health threat caused by multiresistant bacteria has continuously increased
      and recently peaked with pathogens resistant to all current drugs. This has
      triggered intense research efforts to develop novel compounds to overcome the
      resistance mechanisms. Thus, antimicrobial peptides (AMPs) have been intensively
      studied, especially the family of proline-rich AMPs (PrAMPs) that was
      successfully tested very recently in murine infection models. PrAMPs enter
      bacteria and inhibit chaperone DnaK. Here, we studied the toxicity of
      intracellular PrAMPs in HeLa and SH-SY5Y cells. As PrAMPs cannot enter most
      mammalian cells, we coupled the PrAMPs with penetratin (residues 43 to 58 in the
      antennapedia homeodomain) via a C-terminally added cysteine utilizing a thioether
      bridge. The resulting construct could transport the covalently linked PrAMP into
      mammalian cells. Penetratin ligation reduced the MIC for Gram-negative
      Escherichia coli only slightly (1 to 8 MUmol/liter) but increased the activity
      against the Gram-positive Micrococcus luteus up to 32-fold (MIC ~ 1 MUmol/liter),
      most likely due to more effective penetration through the bacterial membrane. In
      contrast to native PrAMPs, the penetratin-PrAMP constructs entered the mammalian
      cells, aligned around the nucleus, and associated with the Golgi apparatus. At
      higher concentrations, the constructs reduced the cell viability (50% inhibitory
      concentration [IC(50)] ~ 40 MUmol/liter) and changed the morphology of the cells.
      No toxic effects or morphological changes were observed at concentrations of 10
      MUmol/liter or below. Thus, the IC(50) values were around 5 to 40 times higher
      than the MIC values. In conclusion, PrAMPs are in general not toxic to mammalian
      cells, as they do not pass through the membrane. When shuttled into mammalian
      cells, however, PrAMPs are only slightly cross-reactive to mammalian chaperones
      or other intracellular mammalian proteins, providing a second layer of safety for
      in vivo applications, even if they can enter some human cells.

PMID- 22850524
TI  - Antibacterial activities of iron chelators against common nosocomial pathogens.
AB  - The activities of iron chelators (deferoxamine, deferiprone, Apo6619, and VK28)
      were evaluated against type strains of Acinetobacter baumannii, Pseudomonas
      aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli.
      Deferiprone, Apo6619, and VK28 each inhibited growth in standard and RPMI tissue
      culture medium, while deferoxamine had no effect. Additionally, time-kill assays
      revealed that VK28 had a bacteriostatic effect against S. aureus. Therefore,
      these newly developed iron chelators might provide a nontraditional approach for
      treatment of bacterial infections.

PMID- 22850525
TI  - Inhibition of human respiratory syncytial virus infectivity by a dendrimeric
      heparan sulfate-binding peptide.
AB  - Respiratory syncytial virus (RSV) interacts with cell surface heparan sulfate
      proteoglycans (HSPGs) to initiate infection. The interaction of RSV with HSPGs
      thus presents an attractive target for the development of novel inhibitors of RSV
      infection. In the present study, a minilibrary of linear, dimeric, and
      dendrimeric peptides containing clusters of basic amino acids was screened with
      the aim of identifying peptides able to bind HSPGs and thus block RSV attachment
      and infectivity. Of the compounds identified, the dendrimer SB105-A10 was the
      most potent inhibitor of RSV infectivity, with 50% inhibitory concentrations
      (IC(50)s) of 0.35 MUM and 0.25 MUM measured in Hep-2 and A549 cells,
      respectively. SB105-A10 was found to bind to both cell types via HSPGs,
      suggesting that its antiviral activity is indeed exerted by competing with RSV
      for binding to cell surface HSPGs. SB105-A10 prevented RSV infection when added
      before the viral inoculum, in line with its proposed HSPG-binding mechanism of
      action; moreover, antiviral activity was also exhibited when SB105-A10 was added
      postinfection, as it was able to reduce the cell-to-cell spread of the virus. The
      antiviral potential of SB105-A10 was further assessed using human-derived
      tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly
      differentiated model of the epithelial tissue of the human respiratory tract.
      SB105-A10 strongly reduced RSV infectivity in this model and exhibited no signs
      of cytotoxicity or proinflammatory effects. Together, these features render SB105
      A10 an attractive candidate for further development as a RSV inhibitor to be
      administered by aerosol delivery.

PMID- 22850526
TI  - Strong magnetic instability in correlated metallic Bi2Ir2O7.
AB  - We report an experimental/theoretical study of single-crystal Bi(2)Ir(2)O(7) that
      possesses a metallic state with strongly exchange-enhanced paramagnetism. The
      ground state of Bi(2)Ir(2)O(7) is characterized  by the following features: (1) a
      divergent low-temperature magnetic susceptibility that indicates no long-range
      order down to 50 mK; (2) strongly field-dependent coefficients of the low
      temperature T and T(3) terms of the specific heat; (3) a conspicuously large
      Wilson ratio R(W) ~ 53.5; and (4) unusual temperature and field dependences of
      the Hall resistivity that abruptly change below 80 K, without any clear
      correlation with the magnetic behavior. All these unconventional properties
      suggest the existence of an exotic ground state in Bi(2)Ir(2)O(7).

PMID- 22850527
TI  - Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia
      of childhood: a whole-exome sequencing gene-identification study.
AB  - BACKGROUND: Alternating hemiplegia of childhood (AHC) is a rare neurological
      disorder characterised by early-onset episodes of hemiplegia, dystonia, various
      paroxysmal symptoms, and developmental impairment. Almost all cases of AHC are
      sporadic but AHC concordance in monozygotic twins and dominant transmission in a
      family with a milder phenotype have been reported. Thus, we aimed to identify de
      novo mutations associated with this disease. METHODS: We recruited patients with
      clinically characterised AHC from paediatric neurology departments in Germany and
      with the aid of a parental support group between Sept, 2004, and May 18, 2012. We
      used whole-exome sequencing of three proband-parent trios to identify a disease
      associated gene and then tested whether mutations in the gene were also present
      in the remaining patients and their healthy parents. We analysed genotypes and
      characterised their associations with the phenotypic spectrum of the disease.
      FINDINGS: We studied 15 female and nine male patients with AHC who were aged 8-35
      years. ATP1A3 emerged as the disease-associated gene in AHC. Whole-exome
      sequencing showed three heterozygous de-novo missense mutations. Sequencing of
      the 21 remaining affected individuals identified disease-associated mutations in
      ATP1A3 in all patients, including six de-novo missense mutations and one de-novo
      splice-site mutation. Because ATP1A3 is also the gene associated with rapid-onset
      dystonia-parkinsonism (DYT12, OMIM 128235) we compared the genotypes and
      phenotypes of patients with AHC in our cohort with those of patients with rapid
      onset dystonia-parkinsonism reported in the scientific literature. We noted
      overlapping clinical features, such as abrupt onset of dystonic episodes often
      triggered by emotional stress, a rostrocaudal (face to arm to leg) gradient of
      involvement, and signs of brainstem dysfunction, as well as clearly
      differentiating clinical characteristics, such as episodic hemiplegia and
      quadriplegia. INTERPRETATION: Mutation analysis of the ATP1A3 gene in patients
      who met clinical criteria for AHC allows for definite genetic diagnosis and sound
      genetic counselling. AHC and rapid-onset dystonia-parkinsonism are allelic
      diseases related to mutations in ATP1A3 and form a phenotypical continuum of a
      dystonic movement disorder. FUNDING: Eva Luise and Horst Kohler Foundation for
      Humans with Rare Diseases.

PMID- 22850528
TI  - Comparative study of cardiac anatomic measurements obtained by echocardiography
      and dual-source computed tomography.
AB  - The aim of this study was to verify the accuracy of echocardiography by dual
      source computed tomography (DSCT). Seven normal beagles underwent DSCT and
      echocardiography. Echocardiographic measurements were obtained according to the
      American Society of Echocardiography guidelines. The DSCT images were
      reconstructed onto the same echocardiographic image plane by using a
      reconstruction program, and then anatomical measurements were obtained.
      Nonparametric analysis was used for verifying the significance of each of the
      measured parameters. The anatomical measurements obtained using echocardiography
      and DSCT were not significant (P>0.05), and the difference between the
      measurements obtained using both the methods were within 95% confidence intervals
      except those for interventricular septal thickness and left ventricular posterior
      wall thickness in end diastole. The reasons for these differences were considered
      to be the adjacent structures such as papillary muscles or chordae tendineae that
      may have influenced the echocardiographic findings, lower far-field image quality
      of echocardiography, low test-retest reproducibility of echocardiography, high
      quality images of DSCT minimizing the motion artifact and the retrospective ECG
      gating technique of DSCT that offered an adequate timing decision for the
      systolic and diastolic phase during cardiac movement. Although there were
      differences in the measurements of interventricular septal thickness and left
      ventricular posterior wall thickness in end diastole obtained using
      echocardiography and DSCT, we could conclude that echocardiographic measurement
      is as accurate and reliable as DSCT for cardiac anatomical assessment.

PMID- 22850530
TI  - Dipeptidyl peptidase 4 as a therapeutic target in ischemia/reperfusion injury.
AB  - Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than
      four decades ago as a serine protease that cleaves off N-terminal dipeptides from
      peptide substrates. The development of potent DPP4 inhibitors during the past two
      decades has led to the identification of DPP4 as a target in the treatment of
      type 2 diabetes. The favorable effect of DPP4 inhibitors is based on prevention
      of the in vivo inactivation of the incretin hormone, glucagon-like peptide-1 (GLP
      1) by DPP4. Apart from GLP-1, a number of other biologically active peptides are
      truncated by DPP4. For these peptides, the physiological relevance of their
      truncation has yet to be fully elucidated. Within the last 10years, DPP4
      inhibitors have been employed in several animal models of lung and heart disease,
      in which injury was induced by an ischemic insult followed by subsequent
      reperfusion. In this review, we present a state-of-the-art of the
      ischemia/reperfusion injury (IRI)-related pharmacological actions of DPP4
      substrates, including GLP-1, stromal cell-derived factor-1 alpha and vasoactive
      intestinal peptide. Furthermore, we discuss the large body of experimental work
      that now provides compelling evidence for the advantageous impact of DPP4
      targeting in IRI. However, possible risks as well as underlying mechanisms are
      yet to be elucidated before translating these promising treatment strategies into
      clinical practice.

PMID- 22850531
TI  - Polyvalent nucleic acid aptamers and modulation of their activity: a focus on the
      thrombin binding aptamer.
AB  - Nucleic acid-based aptamers can be selected from combinatorial libraries of
      synthetic oligonucleotides to bind, with affinity and specificity similar to
      antibodies, a wide range of biomedically relevant targets. Compared to protein
      therapeutics, aptamers exhibit significant advantages in terms of size, non
      immunogenicity and wide synthetic accessibility. Various chemical modifications
      have been introduced in the natural oligonucleotide backbone of aptamers in order
      to increase their half-life, as well as their pharmacological properties. Very
      effective alternative approaches, devised in order to improve both the aptamer
      activity and stability, were based on the design of polyvalent aptamers, able to
      establish multivalent interactions with the target: thus, multiple copies of an
      aptamer can be assembled on the same molecular- or nanomaterial-based scaffold.
      In the present review, the thrombin binding aptamers (TBAs) are analyzed as a
      model system to study multiple-aptamer constructs aimed at improving their
      anticoagulation activity in terms of binding to the target and stability to
      enzymatic degradation. Indeed - even if the large number of chemically modified
      TBAs investigated in the last 20 years has led to encouraging results - a
      significant progress has been obtained only recently with bivalent or engineered
      dendritic TBA aptamers, or assemblies of TBAs on nanoparticles and DNA
      nanostructures. Furthermore, the modulation of the aptamers activity by means of
      tailored drug-active reversal agents, especially in the field of anticoagulant
      aptamers, as well as the reversibility of the TBA activity through the use of
      antidotes, such as porphyrins, complementary oligonucleotides or of external
      stimuli, are discussed.

PMID- 22850532
TI  - Service users as collaborators in mental health research: less stick, more
      carrot.
AB  - Involving service users in research improves its quality and relevance. Many
      research organizations funding and supporting research now ask researchers about
      involvement as part of their application process. Some researchers are facing
      challenges in taking forward involvement as the research infrastructure is not
      always facilitative. Researchers need greater reward and recognition for carrying
      out good quality involvement to encourage more effective processes.

PMID- 22850529
TI  - Current nutraceuticals in the management of osteoarthritis: a review.
AB  - Osteoarthritis (OA) is a progressive degenerative joint disease that has a major
      impact on joint function and quality of life. Nutraceuticals and dietary
      supplements derived from herbs have long been used in traditional medicine and
      there is considerable evidence that nutraceuticals may play an important role in
      inflammation and joint destruction in OA. We review the biological effects of
      some medicinal fruits and herbs - pomegranate, green tea, cat's claw, devil's
      claw, ginger, Indian olibaum, turmeric and ananas - in an attempt to understand
      the pivotal molecular targets involved in inflammation and the joint destruction
      process and to summarize their toxicities and efficacy for OA management. So far
      there is insufficient reliable evidence on the effectiveness of ginger, turmeric
      and ananas. Pomegranate and green tea only have preclinical evidence of efficacy
      due to the lack of clinical data. In vivo and clinical studies are required to
      understand their targets and efficacy in OA. Limited in vitro and in vivo
      evidence is available for cat's claw and Indian olibaum. More extensive studies
      are required before long-term controlled trials of whole cat's claw and Indian
      olibaum extracts, or isolated active compounds, are carried out in patients with
      OA to determine their long-term efficacy and safety. Devil's claw has not been
      rigorously tested to determine its antiarthritic potential in in vitro and in
      vivo models. There is strong clinical evidence of the effectiveness of devil's
      claw in pain reduction. However, high-quality clinical trials are needed to
      determine its effectiveness. No serious side effects have been reported for any
      fruits and herbs. Overall, these studies identify and support the use of
      nutraceuticals to provide symptomatic relief to patients with OA and to be used
      as adjunct therapy for OA management. More high-quality trials are needed to
      provide definitive answers to questions related to their efficacy and safety for
      OA prevention and/or treatment.

PMID- 22850533
TI  - Effects of serum uric acid levels on coronary collateral circulation in patients
      with non-ST elevation acute coronary syndrome.
AB  - OBJECTIVES: The strong relationship between high level of serum uric acid (UA)
      and cardiovascular disease has been shown in many studies. In this study, we
      investigated whether serum UA levels affect coronary collateral circulation (CCC)
      in patients with non-ST elevation acute coronary syndrome. METHODS: The study
      population included 175 patients with non-ST elevation acute coronary syndrome.
      On the first day of admission to the hospital, blood samples were taken and UA
      levels were analyzed for all patients. Coronary angiography was performed on
      patients within 24-72 h. Rentrop collateral classification was performed.
      Patients were divided into two groups on the basis of UA levels: group I
      consisted of 102 patients (90 male, 12 female) with normal UA levels and group II
      consisted of 73 patients (59 male, 14 female) with elevated UA levels. RESULTS:
      Group 2 had a significantly higher rate of poorly developed CCC and a lower rate
      of well-developed CCC compared with group 1 (P=0.003 and 0.001, respectively).
      Patients with poor CCC had significantly higher serum UA levels compared with
      patients with well-developed CCC (6.5+/-1.1 vs. 5.5+/-1.7 mg/dl, P=0.028). Linear
      regression analyses showed that poor CCC development was significantly associated
      with serum UA levels (coefficient=0.22, P=0.005). CONCLUSION: Serum UA level on
      admission is associated with poor CCC development and may be a useful biomarker
      for stratification of risk in patients with non-ST elevation acute coronary
      syndrome.

PMID- 22850534
TI  - Solving the puzzle of Alzheimer disease.
AB  - Managing patients with dementia and Alzheimer disease can be a challenge. Often,
      families and caregivers ask clinicians about the latest treatments. This article
      summarizes the latest evidence-based practice related to pharmacologic and
      nonpharmacologic management of patients with Alzheimer disease.

PMID- 22850535
TI  - Myasthenia gravis: helping patients have better outcomes.
AB  - Myasthenia gravis (MG) is the most common primary disorder of neuromuscular
      transmission. MG can be treated as a chronic disease with medication, surgery,
      plasmapheresis, and I.V. immunoglobulin.

PMID- 22850536
TI  - Efficient expression of Human papillomavirus 16 E7 oncoprotein fused to C
      terminus of Tobacco mosaic virus (TMV) coat protein using molecular chaperones in
      Escherichia coli.
AB  - The Human papillomavirus 16 (HPV16) E7 oncoprotein is a promising candidate for
      development of anti-cancer therapeutic vaccine. We have prepared the expression
      construct carrying mutagenized E7 oncoprotein fused to the C-terminus of Tobacco
      mosaic virus (TMV) coat protein via 15 amino acids beta-sheet linker. The fusion
      protein was expressed in Escherichia coli MC 1061 cells. We have obtained high
      level expression, but most of the protein remained in insoluble inclusion bodies.
      To increase the ratio of soluble protein various molecular chaperones (TF, DnaK
      DnaJ-GrpE, GroEL-GroES) were used. The immunological reactivity of expressed
      recombinant protein was evaluated with anti-E7 and anti-TMV antibodies. The
      distribution of expressed product during ultracentrifugation on sucrose gradient
      was studied.

PMID- 22850537
TI  - Spot identification and quality control in cell-based microarrays.
AB  - Cell-based microarrays are being increasingly used as a tool for combinatorial
      and high throughput screening of cellular microenvironments. Analysis of
      microarrays requires several steps, including microarray imaging, identification
      of cell spots, quality control, and data exploration. While high content image
      analysis, cell counting, and cell pattern recognition methods are established,
      there is a need for new postprocessing and quality control methods for cell-based
      microarrays used to investigate combinatorial microenvironments. Previously,
      microarrayed cell spot identification and quality control were performed
      manually, leading to excessive processing time and potentially resulting in human
      bias. This work introduces an automated approach to identify cell-based
      microarray spots and spot quality control. The approach was used to analyze the
      adhesion of murine cardiac side population cells on combinatorial arrays of
      extracellular matrix proteins. Microarrays were imaged by automated fluorescence
      microscopy and cells were identified using open-source image analysis software
      (CellProfiler). From these images, clusters of cells making up single cell spots
      were reliably identified by analyzing the distances between cells using a density
      based clustering algorithm (OPTICS). Naive Bayesian classifiers trained on
      manually scored training sets identified good and poor quality spots using spot
      size, number of cells per spot, and cell location as quality control criteria.
      Combined, the approach identified 78% of high quality spots and 87% of poor
      quality spots. Full factorial analysis of the resulting microarray data revealed
      that collagen IV exhibited the highest positive effect on cell attachment. This
      data processing approach allows for fast and unbiased analysis of cell-based
      microarray data.

PMID- 22850539
TI  - Induction of the cellular microRNA-29c by influenza virus contributes to virus
      mediated apoptosis through repression of antiapoptotic factors BCL2L2.
AB  - Influenza A virus is a cytolytic virus that induces apoptosis in numerous cell
      types, which contributes to cellular and organ dysfunction. MicroRNAs (miRNAs)
      represent a family of small noncoding RNAs controlling tanslation and
      transcription of many genes. Recent studies have revealed that miR-29c is
      involved in a variety of biological processes, including apoptosis. However, its
      role in influenza A virus infection is not well understood. Here, we report that
      miR-29c is involved in apoptosis induced by influenza A virus infection. We found
      that several apoptosis-associated miRNAs were stimulated in influenza A virus
      infected A549 cells by miRNA array analysis. Within those, miR-29c was
      significantly up-regulated. In silico target prediction analysis revealed
      complementarity of miR-29c to the 3'-untranslated region (UTR) of BCL2L2 mRNA.
      Targeting of BCL2L2 3' UTR by miR-29c was determined by luciferase assay.
      Functional overexpression of miR-29c with miR-29c precursor inhibited BCL2L2
      protein expression. Transfection of miR-29c inhibitor abolished both suppression
      of BCL2L2 protein expression and A549 cells apoptosis induced by influenza A
      virus. Moreover, BCL2L2 overexpression rescued A549 cell death induced by
      influenza A virus infection. These findings indicate that miR-29c-mediated BCL2L2
      suppression is involved in influenza virus-induced cell death in A549 cells.

PMID- 22850540
TI  - Inhibition of the activation of hepatic stellate cells by arundic acid via the
      induction of cytoglobin.
AB  - BACKGROUND: The activation of hepatic stellate cells plays a central role in the
      development of liver fibrosis during chronic liver trauma. The aim of the present
      study was to identify a compound that inhibits the activation process of stellate
      cells. METHODS: Rat primary cultured stellate cells and a human stellate cell
      line (LX-2) were used. The effects of arundic acid on the expression of alpha
      smooth muscle actin, collagen 1alpha1, and cytoglobin were evaluated. RESULTS:
      Arundic acid (300 MUM) inhibited the activation of primary rat stellate cells, as
      determined by morphological transformation and alpha-smooth muscle actin
      expression, after both prophylactic and therapeutic treatment. The level of alpha
      smooth muscle actin mRNA showed a dose-dependent decrease in response to arundic
      acid, and 50 MUM arundic acid exhibited the maximum inhibition of collagen
      1alpha1 mRNA expression. In contrast, arundic acid triggered an unexpected
      increase in mRNA and protein levels of cytoglobin, the fourth globin in mammals
      expressed exclusively in hepatic stellate cells. The effect of arundic acid on
      the level of alpha-smooth muscle actin mRNA was abrogated in HSCs treated with
      cytoglobin siRNA. Arundic acid decreased the expression of collagen 1alpha1 mRNA
      in LX-2 cells. CONCLUSION: Arundic acid affects the activation process of hepatic
      stellate cells via the unexpected induction of cytoglobin.

PMID- 22850541
TI  - The mechanism of hexamethylenetetramine (HMT) formation in the solid state at low
      temperature.
AB  - There is convincing evidence that the formation of complex organic molecules
      occurred in a variety of environments. One possible scenario highlights the
      universe as a giant reactor for the synthesis of organic complex molecules, which
      is confirmed by numerous identifications of interstellar molecules. Among them,
      precursors of biomolecules are of particular significance due to their
      exobiological implications, and some current targets concern their search in the
      interstellar medium as well as understanding the mechanisms of their formation.
      Hexamethylenetetramine (HMT, C(6)H(12)N(4)) is one of these complex organic
      molecules and is of prime interest since its acid hydrolysis seems to form amino
      acids. In the present work, the mechanism for HMT formation at low temperature
      and pressure (i.e. resembling interstellar conditions) has been determined by
      combining experimental techniques and DFT calculations. Fourier transform infra
      red spectroscopy and mass spectrometry techniques have been used to follow
      experimentally the formation of HMT as well as its precursors from thermal
      reaction of NH(3):H(2)CO:HCOOH and CH(2)NH:HCOOH ice mixtures, from 20 K to 330
      K. DFT calculations have been used to compute the mechanistic steps through which
      HMT can be formed starting from the experimental reactants observed in solid
      phase. The fruitful interplay between theory and experiment has allowed
      establishing that the mechanism in the solid state at low temperature is
      different from the one proposed in liquid phase, in which a new intermediate
      (1,3,5-triazinane, C(3)H(9)N(3)) has been identified. In the meantime,
      aminomethanol has been unambiguously confirmed as the first intermediate whereas
      the hypothesis of methylenimine as the second is further strengthened.

PMID- 22850542
TI  - Interstrand disulfide crosslinking of DNA bases supports a double nucleotide
      unpairing mechanism for flap endonucleases.
AB  - Flap endonucleases (FENs) are proposed to select their target phosphate diester
      by unpairing the two terminal nucleotides of duplex. Interstrand disulfide
      crosslinks, introduced by oxidation of thiouracil and thioguanine bases,
      abolished the specificity of human FEN1 for hydrolysis one nucleotide into the 5'
      duplex.

PMID- 22850543
TI  - Physical activity level and risk of death: the severance cohort study.
AB  - BACKGROUND: Physical activity decreases deaths from cardiovascular disease and
      other causes; however, it is unclear whether physical activity is associated with
      cancer incidence and death in Asian populations. METHODS: Data from 59 636
      Koreans aged 30 to 93 years were collected using a questionnaire and medical
      examination at the Severance Hospital Health Promotion Center between 1994 and
      2004. Study participants were followed for a mean duration of 10.3 years.
      RESULTS: In the exercising group, the multivariate Cox proportional hazards model
      showed a lower risk of cancer death (hazard ratio [HR] = 0.72, 95% CI = 0.62
      0.85) in men but not in women. Those who exercised, as compared with those who
      did not, had lower risks of all-cause death (men: HR = 0.68, 95% CI = 0.60-0.76;
      women: HR = 0.65, 95% CI = 0.53-0.79) and noncancer death (men: 0.63, 0.53-0.75;
      women: 0.52, 0.39-0.69). Physical activity was inversely associated with risk of
      noncancer death among men and women. CONCLUSIONS: Physical activity was
      associated with lower risks of cancer death and noncancer death.

PMID- 22850544
TI  - Association between activities of daily living and mortality among
      institutionalized elderly adults in Japan.
AB  - BACKGROUND: We assessed the association between activities of daily living (ADL)
      and mortality among nursing home residents in Japan. METHODS: This 1-year
      prospective cohort study investigated 8902 elderly adults in 140 nursing homes.
      Baseline measurements included age, sex, height, weight, body mass index (BMI),
      ADL, and dementia level. ADL levels were obtained by caregivers, using the
      Barthel Index (BI), after which total BI scores were calculated (higher scores
      indicate less dependence). Information on dates of discharge and mortality was
      also obtained to calculate person-years. The Cox proportional hazards model was
      used to estimate hazard ratios (HRs). RESULTS: Mean age was 84.3 years, and mean
      total BI score was 38.5. The HRs of mortality adjusted for sex, age, BMI, and
      type of nursing home were 7.6 (95% CI: 3.3-17.8) for those with a BI score of 0
      (totally dependent), 3.9 (1.7-9.0) for those with a score of 1 to 10, 3.5 (1.4
      8.7) for those with a score of 11 to 40, 2.7 (1.4-5.1) for those with a score of
      41 to 70, and 1.3 (0.7-2.4) for those with a score of 71 to 99 (P for trend
      <0.001), as compared with those with a score of 100. Multivariate analysis
      revealed that BI, sex, age, and BMI were significantly associated with mortality
      rate. CONCLUSIONS: There was a clear inverse association between ADL level and
      mortality. In conjunction with other risk factors, ADL level might effectively
      predict short-term mortality in institutionalized elderly adults.

PMID- 22850545
TI  - Selected polymorphisms of base excision repair genes and pancreatic cancer risk
      in Japanese.
AB  - BACKGROUND: Although several reports have described a possible association
      between DNA repair genes and pancreatic cancer (PC) in smokers, this association
      has not been fully evaluated in an Asian population. We assessed the impact of
      genetic polymorphisms in the base excision repair (BER) pathway on PC risk among
      Japanese. METHODS: This case-control study compared the frequency of 5 single
      nucleotide polymorphisms (SNPs) of BER genes, namely rs1052133 in OGG1, rs1799782
      and rs25487 in XRCC1, rs1130409 in APE1, and rs1136410 in PARP1. SNPs were
      investigated using the TaqMan assay in 185 PC cases and 1465 controls.
      Associations of PC risk with genetic polymorphisms and gene-environment
      interaction were examined with an unconditional logistic regression model.
      Exposure to risk factors was assessed from the results of a self-administered
      questionnaire. We also performed haplotype-based analysis. RESULTS: We observed
      that the minor allele of rs25487 in XRCC1 was significantly associated with PC
      risk in the per-allele model (odds ratio = 1.29, CI = 1.01-1.65; trend P =
      0.043). Haplotype analysis of XRCC1 also showed a statistically significant
      association with PC risk. No statistically significant interaction between XRCC1
      polymorphisms and smoking status was seen. CONCLUSIONS: Our findings suggest that
      XRCC1 polymorphisms affect PC risk in Japanese.

PMID- 22850546
TI  - Validation of self-reported sleep against actigraphy.
AB  - BACKGROUND: Self-report remains the most practical and cost-effective method for
      epidemiologic sleep studies involving large population-based samples. Several
      validated questionnaires have been developed to assess sleep, but these tools are
      lengthy to administer and may be impractical for epidemiologic studies. We
      examined whether a 3-item sleep questionnaire, similar to those typically used in
      epidemiologic studies, closely corresponded with objective measures of sleep as
      assessed using actigraphy monitoring. METHODS: Eligible participants were Western
      Australian women aged 18 to 80 years. Participants completed a sleep
      questionnaire, wore a wrist actigraph for 7 nights, and completed a brief daily
      sleep log. Objective actigraphy measurements for 56 participants were summarized
      by mean and mode and compared with the subjective reports, using weighted kappa
      and delta. RESULTS: Data collected from the questionnaire showed poor agreement
      with objectively measured sleep, with kappas ranging from -0.19 to 0.14.
      CONCLUSIONS: Our results indicate that sleep questions typically used in
      epidemiologic studies do not closely correspond with objective measures of sleep
      as assessed using actigraphy. The findings have implications for studies that
      have used such sleep questions. A means of appropriately measuring sleep as a
      risk factor in epidemiologic studies remains to be determined.

PMID- 22850547
TI  - On the absence of a positive sound dispersion in the THz dynamics of glycerol: an
      inelastic x-ray scattering study.
AB  - The high frequency transport properties of glycerol are derived from inelastic x
      ray scattering spectra measured at different pressures and compared with
      ultrasound absorption data. As a result, the presence of two distinct relaxation
      processes is inferred: a slow one, occurring in the GHz window and having an
      essentially structural character, and a fast one, related instead to microscopic
      degrees of freedom. While the former originates a neat increase of the apparent,
      i.e. frequency-dependent, sound velocity, the latter induces no visible
      dispersive effects on the acoustic propagation. The observed behavior is likely
      paradigmatic of all glass formers near or below the melting and it is here
      discussed and explained in some detail.

PMID- 22850548
TI  - Neoadjuvant bevacizumab persistently inactivates VEGF at the time of surgery
      despite preoperative cessation.
AB  - BACKGROUND: When anti-VEGF (vascular endothelial growth factor) antibody
      bevacizumab is applied in neoadjuvant treatment of colorectal cancer patients
      with liver metastasis, 5-6 weeks between last bevacizumab dose and liver
      resection are currently recommended to avoid complications in wound and liver
      regeneration. In this context, we aimed to determine whether VEGF is inactivated
      by bevacizumab at the time of surgery. METHODS: Fifty colorectal cancer patients
      with liver metastases received neoadjuvant chemotherapy +/- bevacizumab
      supplementation. The last dose of bevacizumab was administered 6 weeks before
      surgery. Plasma, subcutaneous and intraabdominal wound fluid were analysed for
      VEGF content before and after liver resection (day 1-3). Immunoprecipitation was
      applied to determine the amount of bevacizumab-bound VEGF. RESULTS: Bevacizumab
      treated individuals showed no increase in perioperative complications. During the
      entire monitoring period, plasma VEGF was inactivated by bevacizumab. In wound
      fluid, VEGF was also completely bound by bevacizumab and was remarkably low
      compared with the control chemotherapy group. CONCLUSION: These data document
      that following a cessation time of 6 weeks, bevacizumab is fully active and
      blocks circulating and local VEGF at the time of liver resection. However,
      despite effective VEGF inactivation no increase in perioperative morbidity is
      recorded suggesting that VEGF activity is not essential in the immediate
      postoperative recovery period.

PMID- 22850549
TI  - A retrospective observational study examining the characteristics and outcomes of
      tumours diagnosed within and without of the English NHS Bowel Cancer Screening
      Programme.
AB  - BACKGROUND: Colorectal cancer is common in England and, with long-term survival
      relatively poor, improving outcomes is a priority. A major initiative to reduce
      mortality from the disease has been the introduction of the National Health
      Service (NHS) Bowel Cancer Screening Programme (BCSP). Combining data from the
      BCSP with that in the National Cancer Data Repository (NCDR) allows all tumours
      diagnosed in England to be categorised according to their involvement with the
      BCSP. This study sought to quantify the characteristics of the tumours diagnosed
      within and outside the BCSP and investigate its impact on outcomes. METHODS:
      Linkage of the NCDR and BCSP data allowed all tumours diagnosed between July 2006
      and December 2008 to be categorised into four groups; screen-detected tumours,
      screening-interval tumours, tumours diagnosed in non-participating invitees and
      tumours diagnosed in those never invited to participate. The characteristics,
      management and outcome of tumours in each category were compared. RESULTS: In
      all, 76 943 individuals were diagnosed with their first primary colorectal cancer
      during the study period. Of these 2213 (2.9%) were screen-detected, 623 (0.8%)
      were screening-interval cancers, 1760 (2.3%) were diagnosed in individuals in non
      participating invitees and 72 437 (94.1%) were diagnosed in individuals not
      invited to participate in the programme due to its ongoing roll-out over the time
      period studied. Screen-detected tumours were identified at earlier Dukes' stages,
      were more likely to be managed with curative intent and had significantly better
      outcomes than tumours in other categories. CONCLUSION: Screen-detected cancers
      had a significantly better prognosis than other tumours and this would suggest
      that the BCSP should reduce mortality from colorectal cancer in England.

PMID- 22850550
TI  - Single-visit approach of cervical cancer screening: see and treat in Indonesia.
AB  - BACKGROUND: We performed a cross-sectional study in Indonesia to evaluate the
      performance of a single-visit approach of cervical cancer screening, using visual
      inspection with acetic acid (VIA), histology and cryotherapy in low-resource
      settings. METHODS: Women having limited access to health-care facilities were
      screened by trained doctors using VIA. If the test was positive, biopsies were
      taken and when eligible, women were directly treated with cryotherapy. Follow-up
      was performed with VIA and cytology after 6 months. When cervical cancer was
      suspected or diagnosed, women were referred. The positivity rate, positive
      predictive value (PPV) and approximate specificity of the VIA test were
      calculated. The detection rate for cervical lesions was given. RESULTS: Screening
      results were completed in 22 040 women, of whom 92.7% had never been screened.
      Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect
      CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The
      approximate specificity was 98.1%, and the detection rate for CIN I or greater
      was 2.6%. CONCLUSION: The single-visit approach cervical cancer screening
      performed well, showing See and Treat is a promising way to reduce cervical
      cancer in Indonesia.

PMID- 22850551
TI  - Increased MET and HGF gene copy numbers are associated with trastuzumab failure
      in HER2-positive metastatic breast cancer.
AB  - BACKGROUND: To investigate whether copy number gain of MET or hepatocyte growth
      factor (HGF) affect trastuzumab sensitivity in HER2-positive metastatic breast
      cancer (MBC). METHODS: We analysed 130 HER2-positive MBC treated with trastuzumab
      based therapy. MET and HGF gene copy numbers (GCN) were assessed by fluorescence
      in situ hybridisation (FISH) in primary breast cancer samples. Receiver operating
      characteristic analysis was applied to find the best cutoff point for both MET
      and HGF GCN. RESULTS: MET FISH-positive cases (N=36, mean ?3.72) had a
      significantly higher trastuzumab failure rate (44.4% vs 16.0%; P=0.001) and a
      significantly shorter time to progression (5.7 vs 9.9 months; HR 1.74; P=0.006)
      than MET FISH-negative cases (N=94, mean <3.72). Hepatocyte growth factor GCN was
      evaluated in 84 cases (64.6%). Receiver operating characteristic analysis
      identified 33 HGF FISH-positive patients (mean HGF GCN ?3.01). HGF FISH-positive
      status was significantly associated with higher risk of failure (30.3% vs 7.8%;
      P=0.007) as compared with HGF FISH-negative cases (N=51, mean <3.01). MET and HGF
      FISH-positive status was highly correlated (P<0.001) and combination of both
      biomarkers did not increase predictive value of either considered separately.
      CONCLUSION: High GCNs of MET and HGF associate with an increased risk of
      trastuzumab-based therapy failure in HER2-positive MBC.

PMID- 22850552
TI  - Chronic preoperative pain and psychological robustness predict acute
      postoperative pain outcomes after surgery for breast cancer.
AB  - BACKGROUND: Few epidemiological studies have prospectively investigated
      preoperative and surgical risk factors for acute postoperative pain after surgery
      for breast cancer. We investigated demographic, psychological, pain-related and
      surgical risk factors in women undergoing resectional surgery for breast cancer.
      METHODS: Primary outcomes were pain severity, at rest (PAR) and movement-evoked
      pain (MEP), in the first postoperative week. RESULTS: In 338 women undergoing
      surgery, those with chronic preoperative pain were three times more likely to
      report moderate to severe MEP after breast cancer surgery (OR 3.18, 95% CI 1.45
      6.99). Increased psychological 'robustness', a composite variable representing
      positive affect and dispositional optimism, was associated with lower intensity
      acute postoperative PAR (OR 0.63, 95% CI 0.48-0.82) and MEP (OR 0.71, 95% CI 0.54
      0.93). Sentinel lymph node biopsy (SLNB) and intraoperative nerve division were
      associated with reduced postoperative pain. No relationship was found between
      preoperative neuropathic pain and acute pain outcomes; altered sensations and
      numbness postoperatively were more common after axillary sample or clearance
      compared with SLNB. CONCLUSION: Chronic preoperative pain, axillary surgery and
      psychological robustness significantly predicted acute pain outcomes after
      surgery for breast cancer. Preoperative identification and targeted intervention
      of subgroups at risk could enhance the recovery trajectory in cancer survivors.

PMID- 22850553
TI  - Phase II study of first-line sagopilone plus prednisone in patients with
      castration-resistant prostate cancer: a phase II study of the Department of
      Defense Prostate Cancer Clinical Trials Consortium.
AB  - BACKGROUND: Preclinical studies in prostate cancer (PC) models demonstrated the
      anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is
      the first study to investigate the activity and safety of sagopilone in patients
      with metastatic castration-resistant PC (CRPC). METHODS: Chemotherapy-naive
      patients with metastatic CRPC received sagopilone (one cycle: 16 mg m(-2)
      intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary
      efficacy evaluation was prostate-specific antigen (PSA) response rate (>=50% PSA
      reduction confirmed >=28 days apart). According to the Simon two-stage design,
      >=3 PSA responders were necessary within the first 13 evaluable patients for
      recruitment to continue until 46 evaluable patients were available. RESULTS: In
      all, 53 patients received >=2 study medication cycles, with high compliance. Mean
      individual dose was 15.1+/-1.4 mg m(-2) during initial six cycles, mean dose
      intensity 94+/-9%. The confirmed PSA response rate was 37%. Median overall
      progression-free survival was 6.4 months. The most commonly reported adverse
      events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and
      pain in the extremities (47.2%). Sagopilone was associated with very little
      haematological toxicity. CONCLUSION: This study shows that first-line sagopilone
      has noteworthy anti-tumour activity and a clinically significant level of
      neuropathy for patients with metastatic chemotherapy-naive CRPC.

PMID- 22850556
TI  - Modeling epileptic brain states using EEG spectral analysis and topographic
      mapping.
AB  - Changes in the spatio-temporal behavior of the brain electrical activity are
      believed to be associated to epileptic brain states. We propose a novel
      methodology to identify the different states of the epileptic brain, based on the
      topographic mapping of the time varying relative power of delta, theta, alpha,
      beta and gamma frequency sub-bands, estimated from EEG. Using normalized-cuts
      segmentation algorithm, points of interest are identified in the topographic
      mappings and their trajectories over time are used for finding out relations with
      epileptogenic propagations in the brain. These trajectories are used to train a
      Hidden Markov Model (HMM), which models the different epileptic brain states and
      the transition among them. Applied to 10 patients suffering from focal seizures,
      with a total of 30 seizures over 497.3h of data, the methodology shows good
      results (an average point-by-point accuracy of 89.31%) for the identification of
      the four brain states--interictal, preictal, ictal and postictal. The results
      suggest that the spatio-temporal dynamics captured by the proposed methodology
      are related to the epileptic brain states and transitions involved in focal
      seizures.

PMID- 22850554
TI  - PREDICT Plus: development and validation of a prognostic model for early breast
      cancer that includes HER2.
AB  - BACKGROUND: Predict (www.predict.nhs.uk) is an online, breast cancer
      prognostication and treatment benefit tool. The aim of this study was to
      incorporate the prognostic effect of HER2 status in a new version (Predict+), and
      to compare its performance with the original Predict and Adjuvant!. METHODS: The
      prognostic effect of HER2 status was based on an analysis of data from 10 179
      breast cancer patients from 14 studies in the Breast Cancer Association
      Consortium. The hazard ratio estimates were incorporated into Predict. The
      validation study was based on 1653 patients with early-stage invasive breast
      cancer identified from the British Columbia Breast Cancer Outcomes Unit.
      Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for
      Predict+, Predict and Adjuvant! were compared with observed outcomes. RESULTS:
      All three models performed well for both OS and BCSS. Both Predict models
      provided better BCSS estimates than Adjuvant!. In the subset of patients with
      HER2-positive tumours, Predict+ performed substantially better than the other two
      models for both OS and BCSS. CONCLUSION: Predict+ is the first clinical breast
      cancer prognostication tool that includes tumour HER2 status. Use of the model
      might lead to more accurate absolute treatment benefit predictions for individual
      patients.

PMID- 22850555
TI  - Dietary cadmium exposure and prostate cancer incidence: a population-based
      prospective cohort study.
AB  - BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a
      prostate carcinogen. Cadmium is widely dispersed into the environment and,
      consequently, food is contaminated. METHODS: A population-based cohort of 41 089
      Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to
      assess the association between food frequency questionnaire-based estimates of
      dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer
      (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for
      prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium
      exposure was 19 MUg per day+/-s.d. 3.7. Multivariable-adjusted dietary cadmium
      exposure was positively associated with overall prostate cancer, comparing
      extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24).
      For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for
      localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51)
      for fatal cases. No statistically significant difference was observed in the
      multivariable-adjusted risk estimates between tumour subtypes
      (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08)
      among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever
      smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure
      may have a role in prostate cancer development.

PMID- 22850557
TI  - Modulation of cortical excitability and interhemispheric inhibition prior to
      rhythmic unimanual contractions.
AB  - The objective of this study was to investigate premotor modulation of motor
      cortical excitability between rhythmic unimanual finger contractions. Applying
      TMS at rest prior to an anticipated contraction provides a measure of cortical
      excitability that reflects premotor modulatory drive and is uncontaminated by the
      alterations in spinal and cortical excitability that occur during muscle
      activation. We hypothesized that premotor structures contribute to unimanual
      movement through the modulation of intracortical and interhemispheric inhibitory
      circuits within the primary motor cortex and that this premotor modulation would
      be evident at rest between contractions. Thus, we used transcranial magnetic
      stimulation (TMS) to assess short interval intracortical inhibition (SICI) and
      interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned
      contraction of the right FDI in 10 participants (21.4+/-1.9 years). These
      measures of inhibition were made in three different states: (1) at complete rest
      (with no plan to contract), (2) at rest between rhythmic contractions, and (3)
      during low level contractions. Cortical excitability was enhanced prior to a
      contraction and during a contraction compared to at rest (F2,18=758.3, p<0.001).
      IHI was also increased prior to a contraction compared to at rest and during a
      contraction while SICI was only reduced during a contraction (F2,38=30.3,
      p<0.001).We used this pre-contraction protocol to investigate the cortical
      mechanisms of unimanual control. However, this protocol would be a useful tool to
      investigate any neuromuscular adaptation that may occur as a result of altered
      premotor modulation of cortical excitability, such as neuromuscular fatigue,
      training and movement disorders.

PMID- 22850558
TI  - Cluster-based spike detection algorithm adapts to interpatient and intrapatient
      variation in spike morphology.
AB  - Visual quantification of interictal epileptiform activity is time consuming and
      requires a high level of expert's vigilance. This is especially true for
      overnight recordings of patient suffering from epileptic encephalopathy with
      continuous spike and waves during slow-wave sleep (CSWS) as they can show tens of
      thousands of spikes. Automatic spike detection would be attractive for this
      condition, but available algorithms have methodological limitations related to
      variation in spike morphology both between patients and within a single
      recording. We propose a fully automated method of interictal spike detection that
      adapts to interpatient and intrapatient variation in spike morphology. The
      algorithm works in five steps. (1) Spikes are detected using parameters suitable
      for highly sensitive detection. (2) Detected spikes are separated into clusters.
      (3) The number of clusters is automatically adjusted. (4) Centroids are used as
      templates for more specific spike detections, therefore adapting to the types of
      spike morphology. (5) Detected spikes are summed. The algorithm was evaluated on
      EEG samples from 20 children suffering from epilepsy with CSWS. When compared to
      the manual scoring of 3 EEG experts (3 records), the algorithm demonstrated
      similar performance since sensitivity and selectivity were 0.3% higher and 0.4%
      lower, respectively. The algorithm showed little difference compared to the
      manual scoring of another expert for the spike-and-wave index evaluation in 17
      additional records (the mean absolute difference was 3.8%). This algorithm is
      therefore efficient for the count of interictal spikes and determination of a
      spike-and-wave index.

PMID- 22850559
TI  - A novel use of combined tyrosine hydroxylase and silver nucleolar staining to
      determine the effects of a unilateral intrastriatal 6-hydroxydopamine lesion in
      the substantia nigra: a stereological study.
AB  - Neurotoxic lesions of the nigrostriatal pathway model the deficits found in
      Parkinson's disease. This study used stereology and a novel staining method to
      examine the effects of a partial unilateral striatal 6-hydroxydopamine (6-OHDA)
      lesion on substantia nigra pars compacta (SNpc) dopamine neuron number and
      morphology in rats. Adult male Long-Evans rats were subjected to unilateral
      lesion of the SNpc by intrastriatal microinjection of 6-OHDA (12.5 MUg). Lesions
      were verified by d-amphetamine-stimulated rotation (2.5 mg/kg, sc) by force-plate
      rotometry 7 days post-surgery. Seven days after rotation testing, rats were
      euthanized, and brains were prepared for either histology (n=12) or determination
      of striatal dopamine content by HPLC-EC (n=20). Brains prepared for histology
      were stained for tyrosine hydroxylase (TH) combined with a silver nucleolar
      (AgNOR) stain using a modified protocol developed for stereological assessment.
      The AgNOR counterstain allowed for precise definition of the nucleolus of the
      cells, facilitating both counting and qualitative morphometry of TH-positive
      neurons. Stereological quantitation determined a 54% decrease in TH-positive
      neuron number (P<0.01), and a 14% decrease in neuron volume (P<0.05) on the
      lesioned side. Striatal dopamine concentration was decreased by 92% (P<0.01),
      suggesting that striatal dopamine analysis may overestimate the numbers of SNpc
      neurons lost. These findings demonstrate that combined use of TH and AgNOR
      staining provides improved characterization of 6-OHDA-induced pathology.
      Furthermore, the data suggest that decreased neuronal volume as well as number
      contributes to the functional deficits observed after unilateral intrastriatal 6
      OHDA lesion.

PMID- 22850560
TI  - Highly selective oximation of aldehydes by reusable heterogeneous sandwich-type
      polyoxometalate catalyst.
AB  - The selectivity of oximation of a variety of aliphatic aldehydes and polycyclic
      aromatic aldehydes as substrates has been greatly improved by applying a reusable
      heterogeneous sandwich-type polyoxometalate as catalyst under mild conditions.

PMID- 22850562
TI  - Diabetic peripheral neuropathy in Spontaneously Diabetic Torii-Lepr(fa) (SDT
      fatty) rats.
AB  - Spontaneously Diabetic Torii (SDT) rat is a hereditary model of diabetes.
      Although the SDT rat shows severe diabetic complications, the onset of
      hyperglycemia is late. SDT fatty rat, established by introducing the fa allele of
      the Zucker fatty rat to SDT rat, develops diabetes much faster than SDT rat. In
      the present study, diabetic peripheral neuropathy (DPN) was evaluated to show the
      further usefulness of this animal model. Motor nerve conduction velocity (MNCV)
      was delayed, and the number of sural nerve fibers was decreased in SDT fatty rat.
      Treatment of pioglitazone lowered blood glucose level and prevented delay of MNCV
      in SDT fatty rats. SDT fatty rat is a useful animal model for studies of DPN in
      type 2 diabetes.

PMID- 22850563
TI  - Drug-induced hepatitis following use of octreotide for long-term treatment of
      congenital hyperinsulinism.
AB  - Congenital hyperinsulinism (CHI) is a rare disorder of hypoglycaemia in children
      due to excessive and dysregulated insulin secretion. Octreotide, a somatostatin
      analogue, is used in the treatment of hypoglycaemia in Diazoxide unresponsive
      CHI, but is associated with side effects such as gastrointestinal dysmotility and
      rarely, necrotising enterocolitis. It would be important to recognise rare but
      serious side effects from Octreotide therapy, particularly with long-term use. In
      this report, we have described drug-induced hepatitis with moderately high doses
      of Octreotide in a child with diffuse CHI. While serum alanine transaminase
      levels rose significantly with Octreotide therapy (maximum dose 30 MUg/kg/day),
      hepatitis resolved following discontinuation of medical treatment. Liver enzymes
      should be monitored routinely in children with CHI using long-term Octreotide
      treatment, particularly with high doses. The presence of drug-induced hepatitis
      should prompt discontinuation of Octreotide treatment with likely subsequent
      resolution.

PMID- 22850564
TI  - Peripheral (limb) myokymic discharges in motor neuron disease.
AB  - We present the case of a 28-year-old gentleman who presented with weakness and
      wasting in the right arm. He complained about painful cramps in his left leg but
      there were no sensory, visual or swallowing problems. Neurological examination
      was significant for asymmetric weakness of both upper and lower limbs and deep
      tendon reflexes were asymmetrically brisk. Initial laboratory investigations, MRI
      brain and MRI spine were normal. Electromyography revealed active denervation and
      chronic neurogenic motor unit action potential. Myokymic discharges were noted in
      the left deltoid muscle.

PMID- 22850561
TI  - Bullied no more: when and how DNA shoves proteins around.
AB  - The predominant protein-centric perspective in protein-DNA-binding studies
      assumes that the protein drives the interaction. Research focuses on protein
      structural motifs, electrostatic surfaces and contact potentials, while DNA is
      often ignored as a passive polymer to be manipulated. Recent studies of DNA
      topology, the supercoiling, knotting, and linking of the helices, have shown that
      DNA has the capability to be an active participant in its transactions. DNA
      topology-induced structural and geometric changes can drive, or at least strongly
      influence, the interactions between protein and DNA. Deformations of the B-form
      structure arise from both the considerable elastic energy arising from
      supercoiling and from the electrostatic energy. Here, we discuss how these
      energies are harnessed for topology-driven, sequence-specific deformations that
      can allow DNA to direct its own metabolism.

PMID- 22850565
TI  - A long-term prospective population pharmacokinetic study on imatinib plasma
      concentrations in GIST patients.
AB  - PURPOSE: Imatinib minimal (trough) plasma concentrations after one month of
      treatment have shown a significant association with clinical benefit in patients
      with gastrointestinal stromal tumors (GIST). Considering that a retrospective
      pharmacokinetic analysis has also suggested that imatinib clearance increases
      over time in patients with soft tissue sarcoma and GIST, the primary aim of this
      study was to assess systemic exposure to imatinib at multiple time points in a
      long-term prospective population pharmacokinetic study. As imatinib is mainly
      metabolized in the liver, our secondary aim was to elucidate the potential
      effects of the volume of liver metastases on exposure to imatinib. EXPERIMENTAL
      DESIGN: Full pharmacokinetic blood sampling was conducted in 50 patients with
      GIST on the first day of imatinib treatment, and after one, six, and 12 months.
      In addition, on day 14, and monthly during imatinib treatment, trough samples
      were taken. Pharmacokinetic analysis was conducted using a compartmental model.
      Volume of liver metastases was assessed by computed tomographic (CT) imaging.
      RESULTS: After 90 days of treatment, a significant decrease in imatinib systemic
      exposure of 29.3% compared with baseline was observed (P < 0.01). For every 100
      cm(3) increase of metastatic volume, a predicted decrease of 3.8% in imatinib
      clearance was observed. CONCLUSIONS: This is the first prospective
      pharmacokinetic study in patients with GIST, showing a significant decrease of
      approximately 30% in imatinib exposure after long-term treatment. This means that
      future "trough level - clinical benefit" analyses should be time point specific.
      GIST liver involvement, however, has a marginal effect on imatinib clearance.

PMID- 22850566
TI  - The rectal cancer microRNAome--microRNA expression in rectal cancer and matched
      normal mucosa.
AB  - PURPOSE: miRNAs play a prominent role in a variety of physiologic and pathologic
      biologic processes, including cancer. For rectal cancers, only limited data are
      available on miRNA expression profiles, whereas the underlying genomic and
      transcriptomic aberrations have been firmly established. We therefore, aimed to
      comprehensively map the miRNA expression patterns of this disease. EXPERIMENTAL
      DESIGN: Tumor biopsies and corresponding matched mucosa samples were
      prospectively collected from 57 patients with locally advanced rectal cancers.
      Total RNA was extracted, and tumor and mucosa miRNA expression profiles were
      subsequently established for all patients. The expression of selected miRNAs was
      validated using semi-quantitative real-time PCR. RESULTS: Forty-nine miRNAs were
      significantly differentially expressed (log(2)-fold difference >0.5 and P <
      0.001) between rectal cancer and normal rectal mucosa. The predicted targets for
      these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR,
      insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these
      49 miRNAs seem to be rectal cancer-specific, and have not been previously
      reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144,
      miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338
      3p. Of clinical impact, miR-135b expression correlated significantly with disease
      free and cancer-specific survival in an independent multicenter cohort of 116
      patients. CONCLUSION: This comprehensive analysis of the rectal cancer miRNAome
      uncovered novel miRNAs and pathways associated with rectal cancer. This
      information contributes to a detailed view of this disease. Moreover, the
      identification and validation of miR-135b may help to identify novel molecular
      targets and pathways for therapeutic exploitation.

PMID- 22850567
TI  - ALKBH3 contributes to survival and angiogenesis of human urothelial carcinoma
      cells through NADPH oxidase and tweak/Fn14/VEGF signals.
AB  - PURPOSE: The role and function of a novel human AlkB homologue, ALKBH3, in human
      urothelial carcinoma development were examined. EXPERIMENTAL DESIGN: Biologic
      roles of ALKBH3 were examined by gene silencing analysis using in vitro and in
      vivo siRNA transfection. Immunohistochemical analyses of ALKBH3 and the related
      molecules using human bladder cancer samples were conducted to estimate the
      association with clinicopathologic or prognostic parameters. RESULTS: ALKBH3
      knockdown induced cell cycle arrest at the G1 phase through downregulation of
      NAD(P)H oxidase-2 (NOX-2)-mediated generation of reactive oxygen species (ROS).
      ALKBH3 knockdown reduced VEGF expression by reducing expression of tumor necrosis
      factor-like weak inducer of apoptosis (Tweak) and its receptor, fibroblast growth
      factor-inducible 14 (Fn14). Silencing of ALKBH3 or Tweak significantly suppressed
      invasion and angiogenesis of urothelial carcinoma in vivo as assessed both by a
      chorioallantoic membrane assay and in an orthotopic mouse model. Interestingly,
      not only urothelial carcinoma cells but also vascular endothelial cells within
      cancer foci expressed Fn14, which was strongly reduced by ALKBH3 and Tweak
      knockdown in vivo, suggesting that ALKBH3-dependent expression of Tweak
      stabilizes Fn14. Immunohistochemical examination showed high expression of
      ALKBH3, Tweak, and Fn14 in urothelial carcinoma, especially in high-grade,
      superficially, and deeply invasive carcinomas; moreover, Fn14-positive vessel
      counts within cancer foci were increased in invasive phenotypes. CONCLUSIONS:
      ALKBH3 contributes to development of urothelial carcinomas by accelerating their
      survival, angiogenesis, and invasion through NOX-2-ROS and Tweak/Fn14-VEGF
      signals.

PMID- 22850569
TI  - Long-term outcomes of 1,263 patients with mycosis fungoides and Sezary syndrome
      from 1982 to 2009.
AB  - PURPOSE: The purpose of this prospectively collected single center study cohort
      of 1,263 patients with mycosis fungoides (MF)/Sezary syndrome (SS) is to evaluate
      the significance of stage and risk of disease progression from initial
      presentation and to examine other prognostic factors. PATIENTS AND METHODS: The
      prognostic variables effecting overall survival (OS) were examined in a unique
      prospective cohort of 1,263 patients with MF and SS seen by one investigator at
      MD Anderson Cancer Center (Houston, TX) from 1982 to 2009. Kaplan-Meier estimates
      were used to determine median OS, progression-free survival (PFS), and disease
      specific survival (DSS). Cox proportional hazards regression model assessed
      prognostic factors. RESULTS: Mean age at diagnosis was 55.33 years. Early mycosis
      fungoides (stage IA-IIA) represented 71.5% (903 of 1,263) and advanced (stage IIB
      IVB) 28.5% (360 of 1,263) patients. Progression to a higher stage occurred in 147
      patients (11.6%) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from
      disease occurred in 102 of 1,263 (8.1%) patients. Median OS was 24.44 years, PFS
      was 16 years, and median DSS was not reached. OS and PFS were significantly
      better for early-stage patients with patches (T1a/T2a) than with patches/plaques
      (T1b/T2b). The PFS analyzed in 1,241 patients found that only 337 (27.2%) had
      disease progression or had died from disease. Risk factors associated with
      progression or deaths were advanced age, plaque stage, lactate dehydrogenase
      (LDH) level, and tumor area. CONCLUSIONS: Improved outcome of MF/SS, reflected by
      OS and PFS for all stages, may result from earlier diagnosis, new therapies, and
      aggressive treatment of infections.

PMID- 22850570
TI  - The FN400 is functionally distinct from the N400.
AB  - The FN400 refers to the early midfrontally-distributed difference between ERPs
      elicited by old and new items, which operates in a way consistent with a neural
      marker of familiarity-based recognition. Double dissociations between the FN400
      and a later ERP index of recollection provide some of the most compelling
      evidence in support of dual-process models to date. It has recently been claimed,
      however, that there is no evidence that the FN400 is functionally distinct from
      the N400 index of implicit semantic priming (Voss, J., and Federmeier, K., FN400
      potentials are functionally identical to N400 potentials and reflect semantic
      processing during recognition testing, Psychophysiology, 48, 532-546, 2011),
      challenging inferences made on the basis of this effect. We argue that the design
      employed to make this claim is flawed because it comprised a semantic priming
      manipulation embedded within a continuous recognition test which enabled
      recognition contrasts to be confounded by semantic processes in a number of ways.
      Here, ERPs were recorded from a design which avoided these confounds by employing
      a semantic priming paradigm which also served as the encoding phase for a
      surprise subsequent recognition test phase. An N400 effect elicited in the
      semantic priming task demonstrated the established centro-parietal maximum,
      whereas the difference between correctly responded to old and new ERPs in the
      recognition test was maximal over frontal sites in the same time window. When
      direct comparisons of the electrophysiological correlates of semantic priming and
      episodic recognition are recorded in a paradigm in which the two are not
      confounded, the FN400 reflects a qualitatively distinct effect from the N400.

PMID- 22850568
TI  - Oncogenic BRAF(V600E) promotes stromal cell-mediated immunosuppression via
      induction of interleukin-1 in melanoma.
AB  - PURPOSE: In this study, we assessed the specific role of BRAF(V600E) signaling in
      modulating the expression of immune regulatory genes in melanoma, in addition to
      analyzing downstream induction of immune suppression by primary human melanoma
      tumor-associated fibroblasts (TAF). EXPERIMENTAL DESIGN: Primary human
      melanocytes and melanoma cell lines were transduced to express WT or V600E forms
      of BRAF, followed by gene expression analysis. The BRAF(V600E) inhibitor
      vemurafenib was used to confirm targets in BRAF(V600E)-positive melanoma cell
      lines and in tumors from melanoma patients undergoing inhibitor treatment. TAF
      lines generated from melanoma patient biopsies were tested for their ability to
      inhibit the function of tumor antigen-specific T cells, before and following
      treatment with BRAF(V600E)-upregulated immune modulators. Transcriptional
      analysis of treated TAFs was conducted to identify potential mediators of T-cell
      suppression. RESULTS: Expression of BRAF(V600E) induced transcription of
      interleukin 1 alpha (IL-1alpha) and IL-1beta in melanocytes and melanoma cell
      lines. Further, vemurafenib reduced the expression of IL-1 protein in melanoma
      cell lines and most notably in human tumor biopsies from 11 of 12 melanoma
      patients undergoing inhibitor treatment. Treatment of melanoma-patient-derived
      TAFs with IL-1alpha/beta significantly enhanced their ability to suppress the
      proliferation and function of melanoma-specific cytotoxic T cells, and this
      inhibition was partially attributable to upregulation by IL-1 of COX-2 and the PD
      1 ligands PD-L1 and PD-L2 in TAFs. CONCLUSIONS: This study reveals a novel
      mechanism of immune suppression sensitive to BRAF(V600E) inhibition, and
      indicates that clinical blockade of IL-1 may benefit patients with BRAF wild-type
      tumors and potentially synergize with immunotherapeutic interventions.

PMID- 22850571
TI  - Feasibility of grey matter and white matter segmentation of the upper cervical
      cord in vivo: a pilot study with application to magnetisation transfer
      measurements.
AB  - Spinal cord pathology can be functionally very important in neurological disease.
      Pathological studies have demonstrated the involvement of spinal cord grey matter
      (GM) and white matter (WM) in several diseases, although the clinical relevance
      of abnormalities detected histopathologically is difficult to assess without a
      reliable way to assess cord GM and WM in vivo. In this study, the feasibility of
      GM and WM segmentation was investigated in the upper cervical spinal cord of 10
      healthy subjects, using high-resolution images acquired with a commercially
      available 3D gradient-echo pulse sequence at 3T. For each healthy subject, tissue
      specific (i.e. WM and GM) cross-sectional areas were segmented and total volumes
      calculated from a 15 mm section acquired at the level of C2-3 intervertebral disc
      and magnetisation transfer ratio (MTR) values within the extracted volumes were
      also determined, as an example of GM and WM quantitative measurements in the
      cervical cord. Mean (+/- SD) total cord cross-sectional area (TCA) and total cord
      volume (TCV) of the section studied across 10 healthy subjects were 86.9 (+/-
      7.7) mm(2) and 1302.8 (+/- 115) mm(3), respectively; mean (+/-SD) total GM cross
      sectional area (TGMA) and total GM volume (TGMV) were 14.6 (+/- 1.1) mm(2) and
      218.3 (+/- 16.8) mm(3), respectively; mean (+/- SD) GM volume fraction (GMVF) was
      0.17 (+/- 0.01); mean (+/- SD) MTR of the total WM volume (WM-MTR) was 51.4 (+/-
      1.5) and mean (+/- SD) MTR of the total GM volume (GM-MTR) was 49.7 (+/- 1.6).
      The mean scan-rescan, intra- and inter-observer % coefficient of variation for
      measuring the TCA were 0.7%, 0.5% and 0.5% and for measuring the TGMA were 6.5%,
      5.4% and 12.7%. The difference between WM-MTR and GM-MTR was found to be
      statistically significant (p=0.00006). This study has shown that GM and WM
      segmentation in the cervical cord is possible and the MR imaging protocol and
      analysis method presented here in healthy controls can be potentially extended to
      study the cervical cord in disease states, with the option to explore further
      quantitative measurements alongside MTR.

PMID- 22850572
TI  - Re-examine tumor-induced alterations in hemodynamic responses of BOLD fMRI:
      implications in presurgical brain mapping.
AB  - BACKGROUND: Blood oxygenation level dependent (BOLD) fMRI is used for presurgical
      functional mapping of brain tumor patients. Abnormal tumor blood supply may
      affect hemodynamic responses and BOLD fMRI signals. PURPOSE: To perform a
      multivariate and quantitative investigation of the effect of brain tumors on the
      hemodynamic responses and its impact on BOLD MRI signal time course, data
      analysis in order to better understand tumor-induced alterations in hemodynamic
      responses, and accurately mapping cortical regions in brain tumor patients.
      MATERIAL AND METHODS: BOLD fMRI data from 42 glioma patients who underwent
      presurgical mapping of the primary motor cortex (PMC) with a block designed
      finger tapping paradigm were analyzed, retrospectively. Cases were divided into
      high grade (n = 24) and low grade (n = 18) groups based on pathology. The tumor
      volume and distance to the activated PMCs were measured. BOLD signal time courses
      from selected regions of interest (ROIs) in the PMCs of tumor affected and
      contralateral unaffected hemispheres were obtained from each patient. Tumor
      induced changes of BOLD signal intensity and time to peak (TTP) of BOLD signal
      time courses were analyzed statistically. RESULTS: The BOLD signal intensity and
      TTP in the tumor-affected PMCs are altered when compared to that of the
      unaffected hemisphere. The average BOLD signal level is statistically significant
      lower in the affected PMCs. The average TTP in the affected PMCs is shorter in
      the high grade group, but longer in the low grade tumor group compared to the
      contralateral unaffected hemisphere. Degrees of alterations in BOLD signal time
      courses are related to both the distance to activated foci and tumor volume with
      the stronger effect in tumor distance to activated PMC. CONCLUSION: Alterations
      in BOLD signal time courses are strongly related to the tumor grade, the tumor
      volume, and the distance to the activated foci. Such alterations may impair
      accurate mapping of tumor-affected functional areas when using conventional fixed
      models.

PMID- 22850573
TI  - Evaluation of an improved method of simulating lung nodules in chest
      tomosynthesis.
AB  - BACKGROUND: Simulated pathology is a valuable complement to clinical images in
      studies aiming at evaluating an imaging technique. In order for a study using
      simulated pathology to be valid, it is important that the simulated pathology in
      a realistic way reflect the characteristics of real pathology. PURPOSE: To
      perform a thorough evaluation of a nodule simulation method for chest
      tomosynthesis, comparing the detection rate and appearance of the artificial
      nodules with those of real nodules in an observer performance experiment.
      MATERIAL AND METHODS: A cohort consisting of 64 patients, 38 patients with a
      total of 129 identified pulmonary nodules and 26 patients without identified
      pulmonary nodules, was used in the study. Simulated nodules, matching the real
      clinically found pulmonary nodules by size, attenuation, and location, were
      created and randomly inserted into the tomosynthesis section images of the
      patients. Three thoracic radiologists and one radiology resident reviewed the
      images in an observer performance study divided into two parts. The first part
      included nodule detection and the second part included rating of the visual
      appearance of the nodules. The results were evaluated using a modified receiver
      operating characteristic (ROC) analysis. RESULTS: The sensitivities for real and
      simulated nodules were comparable, as the area under the modified ROC curve (AUC)
      was close to 0.5 for all observers (range, 0.43-0.55). Even though the ratings of
      visual appearance for real and simulated nodules overlapped considerably, the
      statistical analysis revealed that the observers to were able to separate
      simulated nodules from real nodules (AUC values range 0.70-0.74). CONCLUSION: The
      simulation method can be used to create artificial lung nodules that have similar
      detectability as real nodules in chest tomosynthesis, although experienced
      thoracic radiologists may be able to distinguish them from real nodules.

PMID- 22850574
TI  - Long-term outcome of patients with persistent vascular obstruction on computed
      tomography pulmonary angiography 6 months after acute pulmonary embolism.
AB  - BACKGROUND: The incidence and clinical significance of pulmonary residual
      thrombosis 6 months after an acute pulmonary embolism (PE) are still not well
      known. PURPOSE: To evaluate the association between residual vascular obstruction
      and the risk of venous thromboembolism (VTE) recurrence or death. MATERIAL AND
      METHODS: Computed tomography pulmonary angiography (CTPA) was repeated in 97
      consecutive patients 6 months after an acute episode of hemodynamically stable
      pulmonary embolism. We assessed the long-term consequences of residual thrombosis
      on vital status and incidence of recurrent VTE. RESULTS: Six patients were lost
      for follow-up. The remaining 91 patients were classified according to the
      presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary
      vascular obstruction. After a mean +/- SD of 2.91 +/- 0.99 years, there were
      eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ
      in the incidence of death or VTE recurrence. CONCLUSION: Persistent pulmonary
      vascular obstruction on 6-month CTPA did not predict long-term adverse outcome
      events.

PMID- 22850575
TI  - Percutaneous unilateral placement of biliary covered metallic stent in patients
      with malignant hilar biliary obstruction and contralateral portal vein occlusion.
AB  - BACKGROUND: Unilateral biliary metallic stent placement in the lobe with patent
      portal vein seemed to be a safe and effective palliative treatment of patients
      with contralateral portal vein occlusion caused by advanced hilar malignancy,
      obviating bilateral stent placement in these patients, because the hepatic lobe
      with portal vein occlusion ceases to produce bile due to interruption of
      enterohepatic circulation. PURPOSE: To investigate the safety and efficacy of
      percutaneous unilateral expanded polytetrafluoroethylene (ePTFE)-covered stent
      placement in malignant hilar biliary obstruction with contralateral portal vein
      occlusion. MATERIAL AND METHODS: From February 2008 to March 2011, 24 consecutive
      patients with malignant hilar biliary obstruction and unilobar portal vein
      occlusion were enrolled in this prospective study. All patients were treated by
      percutaneous placement of ePTFE-covered stents. RESULTS: Stent deployment was
      technically successful in all patients. Two (8%) patients experienced minor self
      limiting hemobilia. No major complication was noted. Successful internal drainage
      was achieved in 22 (91.6%) patients. Mean serum bilirubin level, which was 12.5
      mg/dl +/- 8.4 before drainage, decreased significantly to 2.7 mg/dl +/- 3.4, 1
      month after stent placement (P < 0.001). Median survival was 191 days (95% CI, 94
      288 days) and cumulative stent patency rates at 1, 3, 6, 9, and 12 months were
      100%, 95%, 95%, 95%, and 71%, respectively. Two (8%) patients presented with
      stent occlusion due to sludge incrustation. Aside from two patients who had died
      within 30 days after stent placement, the other 22 patients demonstrated slight
      decrease in diameter of undrained lobe and did not experience cholangitis nor
      jaundice. CONCLUSION: Unilateral placement of ePTFE-covered stent in the lobe
      with patent portal vein seems to be a safe and effective method for palliative
      treatment of patients with contralateral portal vein occlusion. In addition,
      ePTFE-covered stent placement can prevent tumor ingrowth without functional
      occlusion of segmental bile ducts.

PMID- 22850576
TI  - Three-dimensional double-echo steady-state (3D-DESS) magnetic resonance imaging
      of the knee: establishment of flip angles for evaluation of cartilage at 1.5 T
      and 3.0 T.
AB  - BACKGROUND: The effect of flip angle (FA) on synovial fluid and cartilage signal
      and on image contrast using three-dimensional double-echo steady-state (3D-DESS)
      sequence have only been performed with 1.0-T but not with 1.5-T or 3.0-T
      scanners. PURPOSE: To identify the FA that gives the maximum synovial fluid and
      cartilage values, and to identify the FA at which maximum values of synovial
      fluid-cartilage contrast-to-noise ratio (CNR) in 3D-DESS sequences when 1.5-T and
      3.0-T scanners are used. MATERIAL AND METHODS: Using 3D-DESS with water
      excitation pulse, mid-sagittal plane images of the knees of 10 healthy volunteers
      (5 men, 5 women; age range, 21-42 years) were obtained with FA varying from 10
      degrees  to 90 degrees . Synovial fluid signals, cartilage signals, and
      background were measured at each FA, and the FA that gave the highest synovial
      fluid and cartilage values was obtained. Synovial fluid-cartilage CNR was also
      calculated, and the FA that gave the largest CNR was obtained. RESULTS: At 1.5 T,
      the maximum synovial fluid signal was at FA 90 degrees , and the maximum
      cartilage signal was at FA 30 degrees . Synovial fluid-cartilage CNR was highest
      at FA 90 degrees  (P < 0.05). At 3.0 T, the maximum synovial fluid signal was at
      FA 90 degrees , and the maximum cartilage signal was at FA 20 degrees . Synovial
      fluid-cartilage CNR was highest at FA 90 degrees  (P < 0.05). CONCLUSION: In
      order to improve the visibility of cartilage itself, FA settings of 30 degrees 
      at 1.5 T and 20 degrees  at 3.0 T are apparently ideal. For observing the
      cartilage surface, the most effective FA setting is 90 degrees  for both 1.5 T
      and 3.0 T.

PMID- 22850577
TI  - Clinical usefulness of the triaxial system in super-selective transcatheter
      arterial chemoembolization for hepatocellular carcinoma.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been widely
      performed for inoperable hepatocellular carcinoma (HCC). Super-selective TACE is
      preferable to non-selective therapy and it is important to advance the catheter
      tip as close to the tumor as possible in the feeding artery. A new microcatheter
      with a 1.9-Fr non-tapered tip has recently become available and this new
      microcatheter can be inserted into a 2.7-Fr. microcatheter. It is called the
      triple co-axial (triaxial) system. PURPOSE: To evaluate the clinical usefulness
      of super-selective TACE for HCC using the triaxial system. MATERIAL AND METHODS:
      We evaluated 63 HCCs that underwent super-selective TACE. Requirements for
      inclusion in this study were: (a) HCCs 3 cm or less in diameter; (b) TACE
      performed by a single operator; and (c) no additional treatment in the absence of
      local progression. All patients were followed for more than 1 year after TACE.
      The median follow-up period for surviving patients was 20 months (range, 17-31
      months). The conventional system was used in 35 HCCs (control group), and the
      triaxial system was used in 28 (triaxial group). We reviewed angiographies at
      TACE and follow-up CT, and then evaluated local tumor status in the two groups.
      RESULTS: Local tumor control rates at 3, 6, and 18 months were 64%, 36%, and 29%,
      respectively, in the triaxial group, and 40%, 14%, and 8.6%, respectively, in the
      control group (P = 0.0086). There were no major complications in either group.
      CONCLUSION: The triaxial system appears to be useful for super-selective TACE and
      may contribute to achieving higher local control rates for HCC.

PMID- 22850578
TI  - The smartest materials: the future of nanoelectronics in medicine.
AB  - Electronics have become central to many aspects of biomedicine, ranging from
      fundamental biophysical studies of excitable tissues to medical monitoring and
      electronic implants to restore limb movement. The development of new materials
      and approaches is needed to enable enhanced tissue integration, interrogation,
      and stimulation and other functionalities. Nanoscale materials offer many avenues
      for progress in this respect. New classes of molecular-scale bioelectronic
      interfaces can be constructed using either one-dimensional nanostructures, such
      as nanowires and nanotubes, or two-dimensional nanostructures, such as graphene.
      Nanodevices can create ultrasensitive sensors and can be designed with spatial
      resolution as fine as the subcellular regime. Structures on the nanoscale can
      enable the development of engineered tissues within which sensing elements are
      integrated as closely as the nervous system within native tissues. In addition,
      the close integration of nanomaterials with cells and tissues will also allow the
      development of in vitro platforms for basic research or diagnostics. Such lab-on
      a-chip systems could, for example, enable testing of the effects of candidate
      therapeutic molecules on intercellular, single-cell, and even intracellular
      physiology. Finally, advances in nanoelectronics can lead to extremely
      sophisticated smart materials with multifunctional capabilities, enabling the
      spectrum of biomedical possibilities from diagnostic studies to the creation of
      cyborgs.

PMID- 22850579
TI  - Protein degradation in bovine milk caused by Streptococcus agalactiae.
AB  - Streptococcus (Str.) agalactiae is a contagious mastitis bacterium, often
      associated with cases of subclinical mastitis. Different mastitis bacteria have
      been evaluated previously from a diagnostic point of view, but there is a lack of
      knowledge concerning their effect on milk composition. Protein composition is
      important in achieving optimal yield and texture when milk is processed to
      fermented products, such as cheese and yoghurt, and is thus of great economic
      value. The aim of this in vitro study was to evaluate protein degradation mainly
      caused by exogenous proteases originating from naturally occurring Str.
      agalactiae. The samples were incubated at 37 degrees C to imitate degradation
      caused by the bacteria in the udder. Protein degradation caused by different
      strains of Str. agalactiae was also investigated. Protein degradation was
      observed to occur when Str. agalactiae was added to milk, but there were
      variations between strains of the bacteria. Caseins, the most economically
      important proteins in milk, were degraded up to 75% in milk inoculated with Str.
      agalactiae in relation to sterile ultra-high temperature (UHT) milk, used as
      control milk. The major whey proteins, alpha-lactalbumin and beta-lactoglobulin,
      were degraded up to 21% in relation to the sterile control milk. These results
      suggest that different mastitis bacteria but also different strains of mastitis
      bacteria should be evaluated from a milk quality perspective to gain knowledge
      about their ability to degrade the economically important proteins in milk.

PMID- 22850580
TI  - Identification of Clostridium beijerinckii, Cl. butyricum, Cl. sporogenes, Cl.
      tyrobutyricum isolated from silage, raw milk and hard cheese by a multiplex PCR
      assay.
AB  - Late blowing, caused by the outgrowth of clostridial spores present in raw milk
      and originating from silage, can create considerable product loss, especially in
      the production of hard and semi-hard cheeses. The conventional method for the
      isolation of Clostridium spp. from cheeses with late-blowing symptoms is very
      complicated and the identification of isolates is problematic. The aim of this
      work was the development of a multiplex PCR method for the detection of the main
      dairy-related clostridia such as: Cl. beijerinckii, Cl. butyricum, Cl.
      sporogenes, Cl. tyrobutyricum. Samples derived from silage, raw milk and hard
      cheese were analysed by the most probable number (MPN) enumeration. Forty-four
      bacterial strains isolated from gas positive tubes were used to check the
      reliability of the multiplex PCR assay. The specificity of the primers was tested
      by individually analysing each primer pair and the primer pair combined in the
      multiplex PCR. It was interesting to note that the samples not identified by the
      multiplex PCR assay were amplified by V2-V3 16S rRNA primer pair and the
      sequencing revealed the aligned 16S rRNA sequences to be Paenibacillus and
      Bacillus spp. This new molecular assay provides a simple promising alternative to
      traditional microbiological methods for a rapid, sensitive detection of
      clostridia in dairy products.

PMID- 22850581
TI  - Pathogen-group specific association between CXCR1 polymorphisms and subclinical
      mastitis in dairy heifers.
AB  - The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous
      receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes
      (PMNL). Binding causes migration from blood to milk, activation and prolonged
      survival of PMNL, a crucial process in the innate immune defence of the bovine
      mammary gland against invading mastitis-causing pathogens. The main objective of
      this study was to screen the entire coding region of the CXCR1 gene for
      polymorphisms and to analyse their association with udder health of dairy
      heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20
      commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data
      on udder health was available including quarter bacteriological culture results
      and somatic cell count (SCC) in early lactation and composite milk SCC during
      first lactation. In total, 16 polymorphisms (including 8 missense mutations) were
      detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI:
      heifers with genotype AG were less likely to have an IMI due to major mastitis
      pathogens compared with heifers with genotype GG but did not have less IMI by
      coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was
      neither associated with quarter SCC in early lactation nor with composite SCC
      during lactation. Although mastitis susceptibility is influenced by many factors,
      some genetic polymorphisms potentially have major effects on udder health of
      heifers, as was shown here. These results trigger us to further study the
      relationship between CXCR1 polymorphisms and mastitis susceptibility in both
      observational and experimental trials.

PMID- 22850582
TI  - Influence of dry period length on reproductive performance and productivity of
      Lacaune dairy sheep under an intensive management system.
AB  - Intensive management is almost the only way to ensure dairy farm profitability.
      The dry period length (DPL) is a key factor in the productivity and health of
      dairy cows, but whether the same is true of dairy sheep is unclear. This study
      investigated the effects of DPL on the performance of Lacaune sheep under
      intensive management. We recorded 8136 lactations from 4220 ewes on one farm for
      the period 2005-2010, and data from a total of 6762 complete lactations 1-4 were
      included in the study. The length of the dry period following the current
      lactation was studied. The larger the total milk yield (MY) and daily milk yield
      (DMY), the shorter was the DPL before the next lactation. DPL correlated with MY
      (r=-0.384), DMY (r=-0.277) and the lambing-to-conception interval (LC; r=0.201,
      P<0.0001) in the global analysis of all lactations (lactations 1-4). The
      influence of previous-DPL (P-DPL), or the length of the period prior to the start
      of the next lactation, was studied for 4318 lactations. P-DPL was classified into
      five intervals: very short (P-DPL-XS), 1-30 d; short (P-DPL-S), 31-60 d; medium
      (P-DPL-M), 61-90 d; long (P-DPL-L), 91-120 d; and very long (P-DPL-XL), >120 d. P
      DPL positively correlated with lambing-to-next conception interval (LNC; r=0.095,
      P<0.0001) for lactations 1-4. LNC was significantly shorter for P-DPLs that were
      very short, short, or long (P-PDL-XS, 144.2+/-67.8 d; P-PDL-S, 149.1+/-57.2 d; P
      PDL-L, 152.0+/-53.7 d) than for groups with very long or medium P-PDLs (P-DPL-XL,
      161.5+/-62.9 d; P-DPL-M, 169.0+/-74.8 d; P<0.0001). Moreover, P-DPLs that were
      very short, long, or very long were associated with the lowest milk yields (P-PDL
      XS, 377+/-215 l; P-PDL-l, 370+/-168 l; P-PDL-XL, 396+/-196 l). These yields were
      significantly lower than the yields for short and medium P-DPLs (P-DPL-S, 432+/
      187 l; P-DPL-M, 436+/-191 l; P<0.0001) when averages of lactations 1-4 were
      analysed. These results indicate that lactations with larger MY are followed by a
      shorter dry period, and that a dry period of 30-90 d leads to larger yields in
      the next lactation. The best LNC was associated with the shortest Previous-DPL.
      Hence, 30-60 d should be the optimal dry period length for Lacaune sheep under
      intensive conditions.

PMID- 22850583
TI  - Ultrasonication and the quality of human milk: variation of power and time of
      exposure.
AB  - Donor human milk is pasteurized to prevent the potential risk of the transmission
      of pathogens to preterm infants. Currently, Holder pasteurization (human milk
      held at 62.5 degrees C for 30 min) is used in most human milk banks, but has the
      disadvantage that it results in excessive inactivation of important bioactive
      components. Power-ultrasound (20-100 kHz) is an emerging technology for the
      preservation of foods and could be an alternative method for the treatment of
      human milk. The aim of this study was to investigate the effect of different
      ultrasound settings on the elimination of Escherichia coli and the retention of
      bile salt stimulated lipase (BSSL) activity. Ultrasonication with a constant
      power decreased Esch. coli viability exponentially over time until the processing
      temperature increased to sub-pasteurization level to between 51.4 and 58.5
      degrees C, then a log10 1.3 decrease was observed (P<0.05). BSSL activity
      decreased to 91% until a temperature of 51.4 degrees C and then it decreased to
      8% between 51.4 and 64.9 degrees C. Ultrasonication with a constant energy and
      various power and exposure times showed the highest temperature (53.7 degrees C)
      when treated with the longest exposure time and lowest ultrasound-power (276 s at
      3.62 W) compared with 37.6 degrees C for 39 s at 25.64 W. The findings predict
      that the viability of Esch. coli could be reduced by log10 5 with a minimal loss
      of activity of BSSL by applying 13.8 kJ of energy in 12 ml of human milk using
      high ultrasound power over a short exposure time to ensure that the temperature
      remains below the critical level for protein denaturation. Alternatively, the use
      of lower power settings such as the 26 W used in the present studies would
      require a cooling system to ensure the human milk BSSL was protected against
      temperature denaturation.

PMID- 22850584
TI  - Additive and dominance effects of the alpha(s1)-casein locus on milk yield and
      composition traits in dairy goats.
AB  - The objective of this study was to evaluate the effects of the CSN1S1 locus
      polymorphism on 305-d records of milk, fat, protein, lactose and total solids
      yields, fat, protein, lactose and total solids contents in Mexican dairy goats. A
      total of 514 lactation records belonging to Alpine (n=60), Saanen (n=105) and
      Toggenburg (n=74) goats, born from 2003 to 2006 in three herds were used.
      Discrimination between alleles E, F, N, A* (CSN1S1 A, G, H, I, O1 and O2) and B*
      (CSN1S1 B1, B2, B3, B4, C and L) were made by amplification of fragments of the
      gene CSN1S1 and digestion with the restriction endonuclease XmnI. In order to
      estimate additive and dominance effects, data sets including (1) all genotypes,
      and (2) only homozygote genotypes, were analysed using linear mixed models. The
      allele A*, had significant additive effects for protein content (0.21+/-0.07%;
      P=0.002) and total solids content (0.66+/-0.23%; P=0.005) when compared with
      allele F. An unfavourable additive effect of allele A* on milk yield was found in
      the Alpine breed (-81.4+/-40.2; P=0.046) when compared with allele F. Favourable
      dominance effects were found for some genotypes (P<0.05) for milk yield (A*N and
      B*N), fat yield (A*N and B*E), protein yield (A*N and B*E), lactose yield (A*N)
      and total solids yield (A*N). Also, unfavourable dominance effects were found
      (P<0.05) for protein content (A*B* and A*N) and total solids content (A*B*, A*N,
      and A*F). Allele A* was the only one with a positive effect for protein content.
      Significant allele-year interaction effects were also observed. The presence of
      significant dominance effects, estimated between specific pairs of alleles,
      challenged the purely additive nature of the genetic effect at the CSN1S1 locus.
      Implications from use of CSN1S1 effects in goat breeding programmes are
      presented.

PMID- 22850585
TI  - Effect of mid-line or low-line milking systems on milking characteristics in
      goats.
AB  - Two experiments were carried out to compare mechanical milking in mid-level (ML)
      and low-level (LL) milkline in goats. The first trial used 40 intramammary
      infection (IMI)-free goats that had been milked in ML during a pre-experimental
      period of 4+/-1 weeks post partum. These animals were divided into two groups
      (n=20), randomly assigning each group to ML or LL milking for a 17-week
      experimental period. During this period, several strategies were applied to
      increase teat exposure to pathogens in both experimental groups. The IMI rate was
      the same in both experimental groups (30% of goats), although the majority of new
      infections appeared earlier in ML (weeks 1-5) than in LL (weeks 7-16). Teat-end
      vacuum range (maximum minus minimum vacuum) was higher in ML than in LL, but no
      significant differences were found in the remaining variables [milk production
      and composition, somatic cell count (SCC), frequency of liner slips+teatcups fall
      off]. In the second experiment, in a crossover design (54 goats in fourth month
      of lactation; 2 treatments, ML and LL, in 2 experimental periods each lasting 1
      week) it was observed that both the milk fractioning (reduced machine milk and
      increased machine stripping) and average machine milk flow worsened slightly in
      ML milking; in contrast, no differences were observed in total milking time or
      teat thickness changes after milking. It was concluded that the differences found
      between ML and LL are not sufficiently important to discourage breeders from
      using ML in goat milking.

PMID- 22850590
TI  - Simulation of phase boundaries using constrained cell models.
AB  - Despite impressive advances, precise simulation of fluid-fluid and fluid-solid
      phase transitions still remains a challenging task. The present work focuses on
      the determination of the phase diagram of a system of particles that interact
      through a pair potential, phi(r), which is of the form phi(r) =
      4epsilon[(sigma/r)(2n) - (sigma/r)(n)] with n = 12. The vapor-liquid phase
      diagram of this model is established from constant-pressure simulations and flat
      histogram techniques. The properties of the solid phase are obtained from
      constant-pressure simulations using constrained cell models. In the constrained
      cell model, the simulation volume is divided into Wigner-Seitz cells and each
      particle is confined to moving in a single cell. The constrained cell model is a
      limiting case of a more general cell model which is constructed by adding a
      homogeneous external field that controls the relative stability of the fluid and
      the solid phase. Fluid-solid coexistence at a reduced temperature of 2 is
      established from constant-pressure simulations of the generalized cell model. The
      previous fluid-solid coexistence point is used as a reference point in the
      determination of the fluid-solid phase boundary through a thermodynamic
      integration type of technique based on histogram reweighting. Since the
      attractive interaction is of short range, the vapor-liquid transition is
      metastable against crystallization. In the present work, the phase diagram of the
      corresponding constrained cell model is also determined. The latter is found to
      contain a stable vapor-liquid critical point and a triple point.

PMID- 22850586
TI  - In reply to Vergier et al: fluorescence in situ hybridization, a diagnostic aid
      in ambiguous melanocytic tumors: European study of 113 cases.

PMID- 22850591
TI  - Optimized synthesis and characterization of N-acylethanolamines and O
      acylethanolamines, important family of lipid-signalling molecules.
AB  - The endocannabinoid anandamide (N-arachidonoylethanolamine, AEA), a
      physiologically occurring bioactive compound on CB1 and CB2 receptors, has
      multiple physiological functions. Since the discovery of AEA additional non
      cannabinoid endogenous compounds such as N-palmitoylethanolamine (PEA), and N
      oleoylethanolamine (OEA) have been identified from mammalian tissues. Virodhamine
      (O-arachidonoylethanolamine, VA) is the only identified new member of the
      endocannabinoid family that is characterised by an ester linkage between acylic
      acid and ethanolamine instead of the amide linkage found in AEA and others non
      cannabinoid N-acylethanolamines. It has been reported, as a cautionary note for
      lipid analyses, that VA can be produced nonenzymatically from AEA (and vice
      versa) as consequence of O,N-acyl migrations. O,N-acyl migrations are well
      documented in synthetic organic chemistry literature, but are not well described
      or recognized with regard to methods in lipid isolation or lipid enzyme studies.
      We here report an economical and effective protocol for large scale synthesis and
      characterization of some N- and O-acylethanolamines that could be useful as
      reference standards in order to investigate their possible formation in
      biological membranes, with potentially interesting biological properties.

PMID- 22850592
TI  - Activation of n-3 polyunsaturated fatty acids as oxime esters: a novel approach
      for their exclusive incorporation into the primary alcoholic positions of the
      glycerol moiety by lipase.
AB  - A novel approach has been developed for activating the highly bioactive long
      chain n-3 polyunsaturated fatty acids EPA and DHA as oxime esters and
      incorporating them exclusively to the end-positions of glycerol and enantiopure 1
      O-alkylglycerols. The Candida antarctica lipase B was observed to display a
      superb regioselectivity when using the acetoxime esters of EPA and DHA as
      acyldonors under mild condition to keep acyl-migration side-reaction under
      complete control. Regiopure 1,3-diacylglycerols, 1-O-alkyl-3-acyl-sn-glycerols
      and their antipodes possessing EPA and DHA were afforded in very high purity and
      yields.

PMID- 22850593
TI  - The importance of dye chemistry and TiCl4 surface treatment in the behavior of
      Al2O3 recombination barrier layers deposited by atomic layer deposition in solid
      state dye-sensitized solar cells.
AB  - Atomic layer deposition (ALD) was used to fabricate Al(2)O(3) recombination
      barriers in solid-state dye-sensitized solar cells (ss-DSSCs) employing an
      organic hole transport material (HTM) for the first time. Al(2)O(3) recombination
      barriers of varying thickness were incorporated into efficient ss-DSSCs utilizing
      the Z907 dye adsorbed onto a 2 MUm-thick nanoporous TiO(2) active layer and the
      HTM spiro-OMeTAD. The impact of Al(2)O(3) barriers was also studied in devices
      employing different dyes, with increased active layer thicknesses, and with
      substrates that did not undergo the TiCl(4) surface treatment. In all instances,
      electron lifetimes (as determined by transient photovoltage measurements)
      increased and dark current was suppressed after Al(2)O(3) deposition. However,
      only when the TiCl(4) treatment was eliminated did device efficiency increase; in
      all other instances efficiency decreased due to a drop in short-circuit current.
      These results are attributed in the former case to the similar effects of
      Al(2)O(3) ALD and the TiCl(4) surface treatment whereas the insulating properties
      of Al(2)O(3) hinder charge injection and lead to current loss in TiCl(4)-treated
      devices. The impact of Al(2)O(3) barrier layers was unaffected by doubling the
      active layer thickness or using an alternative ruthenium dye, but a metal-free
      donor-pi-acceptor dye exhibited a much smaller decrease in current due to its
      higher excited state energy. We develop a model employing prior research on
      Al(2)O(3) growth and dye kinetics that successfully predicts the reduction in
      device current as a function of ALD cycles and is extendable to different dye
      barrier systems.

PMID- 22850594
TI  - Duration of exercise as a key determinant of improvement in insulin sensitivity
      in type 2 diabetes patients.
AB  - Exercise duration and intensity are important parameters in exercise prescription
      and play a major role in improving insulin sensitivity (including transient and
      persistent improvement effects following cessation of training) in patients with
      type 2 diabetes mellitus (T2DM). However, whether duration or intensity of
      exercise is the more important factor has yet to be established. Therefore, we
      aimed to determine whether exercise prescriptions differing in duration and
      intensity differ in their ability to aid T2DM patients to retain insulin
      sensitivity following the conclusion of a period of training. Sedentary T2DM
      patients (age 51.2 +/- 1.3 years) were assigned to either a low-intensity (50%
      VO(2peak), n = 27) or a high-intensity exercise group (75% VO(2peak), n = 28),
      and followed a 12-week exercise program of 5 sessions/week and 240 kcal/session.
      Insulin sensitivity (oral glucose tolerance test, ISI) was measured when subjects
      were sedentary and at 16-24 h and 15 days after the final training bout. The low
      intensity group spent more training time to training per exercise session than
      the high-intensity group (56.1 +/- 3.0 min/session vs. 34.3 +/- 2.4 min/session)
      (P < 0.01), but the total amount of energy expended was the same. ISI was
      increased in both groups 16-24 h after the final training session, but only the
      low-intensity group still had elevated ISI 15 days after the cessation of
      training. These findings suggest that in T2DM patients, the persistent training
      induced improvements in insulin sensitivity may be more dependent on exercise
      duration than exercise intensity in regimens with the same level of energy
      expenditure.

PMID- 22850595
TI  - Visceral adipose tissue volume estimated at imaging sites 5-6 cm above L4-L5 is
      optimal for predicting cardiovascular risk factors in obese Japanese men.
AB  - The association between visceral adipose tissue (VAT) with cardiovascular disease
      (CVD) has been clearly demonstrated.  Although typical VAT area at 4th and 5th
      lumbar vertebrae (L4-L5) is used to approximate VAT volume, growing evidence has
      suggested that this measurement site may not be ideal.  However, these findings
      for Asian people remain unclear.  Thus, we searched for the better VAT
      measurement sites associated with CVD risk factors in obese, Japanese men. 
      Eighty-two obese men were included in a cross-sectional study.  Among these
      participants, 37 men completed the 12-week intervention (90 min and 3 d/week)
      were used for addressing longitudinal association between the VAT measurement
      sites and CVD risk factors.  Consecutive MRI images (from 3 cm below L4-L5 to 20
      cm above L4-L5) were used to explore the relationship between each VAT area and
      CVD risk factors (total cholesterol, HDL cholesterol, triglycerides, glucose,
      insulin and blood pressure).  The images located only 5-9 cm above L4-L5 had
      significant correlations with HDL cholesterol and triglycerides, but L4-L5 site
      did not in the cross-sectional analysis.  In response to exercise, the image
      located 5 cm above L4-L5 showed the highest correlations with changes in total
      cholesterol (r = 0.46) and glucose (r = 0.36).  Also, the image located 6 cm
      above L4-L5 showed highest correlations with changes in triglycerides (r = 0.37)
      and insulin (r = 0.37).  Thus, the range of VAT images located 5-6 cm above L4-L5
      may be optimal for identifying CVD risk factors compared to a typical site of L4
      L5.

PMID- 22850596
TI  - Organic acid induced olefination reaction of lactones.
AB  - (Z)-Selective olefination of several lactones with ketene silyl acetals was
      achieved by the catalysis of carbon acids (C-H acids) having a bis(triflyl)methyl
      group as an acidic functionality; in particular, the triple carbon acid having
      three bis(triflyl)methyl groups in phloroglucinol shows an excellent catalytic
      performance.

PMID- 22850597
TI  - Berberine inhibits growth and induces G1 arrest and apoptosis in human
      cholangiocarcinoma QBC939 cells.
AB  - The chemotherapeutic approach using non-toxic natural products may be one of the
      strategies for the management of the cholangiocarcinoma. Here we report that in
      vitro treatment of human cholangiocarcinoma QBC939 cells with berberine, a
      naturally occurring isoquinoline alkaloid, decreased cell viability and induced
      cell death in a dose-dependent manner, which was associated with an increase in
      G1 arrest. Our western blot analysis showed that berberine-induced G1 cell cycle
      arrest was mediated through the increased expression of cyclin-dependent kinase
      inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in
      Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. In
      additional studies, treatment of QBC939 cells with different concentrations (10,
      40, 80 MUM) of berberine for 48 h resulted in a significant dose-dependent
      increase in apoptosis compared to the non-berberine-treated control, which was
      associated with an increased expression of pro-apoptotic protein Bax and
      decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Together, this
      study for the first time identified berberine as a chemotherapeutic agent against
      human cholangiocarcinoma cells QBC939 cells in vitro. Further in vivo studies are
      required to determine whether berberine could be an effective chemotherapeutic
      agent for the management of cholangiocarcinoma.

PMID- 22850598
TI  - Paclitaxel-induced endothelial dysfunction in living rats is prevented by
      nicorandil via reduction of oxidative stress.
AB  - Paclitaxel-eluting stents dramatically reduce rates of in-stent restenosis;
      however, paclitaxel is known to lead to endothelial dysfunction. Protective
      effects of nicorandil on paclitaxel-induced endothelial dysfunction by examining
      flow-mediated dilation (FMD) were investigated in anesthetized rats. After 7-day
      osmotic infusion of paclitaxel (5 mg/kg per day), FMD was measured by high
      resolution ultrasound in the femoral artery of living rats. Paclitaxel
      significantly reduced FMD (21.6% +/- 3.2% to 7.1% +/- 1.7%); this reduction was
      prevented by co-treatment with nicorandil (15 mg/kg per day), while paclitaxel
      did not affect nitroglycerin-induced vasodilation. Diazoxide and tempol, but not
      isosorbide dinitrate, had an effect similar to nicorandil in preventing
      paclitaxel-induced decrease in FMD. Nicorandil significantly prevented paclitaxel
      induced reduction in acetylcholine-induced vasodilation. On the underling
      mechanisms, paclitaxel increased reactive oxygen species (ROS) production
      (dihydrorhodamine 123, DCF fluorescence intensity) and NADPH oxidase (p47(phox),
      gp91(phox) mRNA) in arteries and human coronary artery endothelial cells
      (HCAECs), while paclitaxel reduced nitric oxide (NO) release (DAF-2 fluorescence
      intensity), but not endothelial NO synthase (eNOS) phosphorylation in HCAECs.
      Nicorandil prevented the increased ROS production in arteries and HCAECs, which
      was 5-hydroxydecanoate (5-HD)-sensitive but 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin
      1-one (ODQ)-resistant, without significant effect on the reduced NO release. In
      conclusion, nicorandil prevents paclitaxel-induced endothelial dysfunction, which
      may be brought by improved NO bioavailability due to the reduction of oxidative
      stress via K(ATP) channel activation.

PMID- 22850599
TI  - CFTR inhibitors for treating diarrheal disease.
AB  - Secretory diarrhea remains a major health challenge worldwide. Excessive fluid
      secretion in the intestine caused by enterotoxins results in activation of
      luminal Cl- channels on enterocytes. The cystic fibrosis transmembrane
      conductance regulator (CFTR) protein is the major cyclic adenosine monophosphate
      (cAMP)-regulated Cl- channel activated in cholera as well as in diarrheas caused
      by other bacterial enterotoxins. Small-molecule screens have yielded CFTR
      inhibitors with half-maximal inhibitory concentration (IC50) values as low as 4
      nmol/l. The data from proof-of-concept studies in animal models support the
      development of CFTR inhibitors for antidiarrheal therapy.

PMID- 22850600
TI  - Molecular targets for the treatment of fibrosing cholangiopathies.
AB  - Emerging pathophysiologic insights are leading to novel approaches to treating
      fibrosing cholangiopathies. The current treatment, using ursodeoxycholic acid
      (UDCA), may slow the progression of some chronic cholangiopathies but cannot heal
      them. Apart from immunosuppressive interventions aimed at minimizing immune
      mediated damage, the use of specific modifiers of hepatobiliary secretory and
      cytoprotective mechanisms may eventually give rise to a new class of disease
      modifying anti-cholangiofibrotic drugs.

PMID- 22850601
TI  - Predictive genetic testing for drug-induced liver injury: considerations of
      clinical utility.
AB  - Genetic predisposition to drug-induced liver injury may be due to variation in
      both pharmacokinetic and pharmacodynamic pathways. Recent genome-wide association
      studies have identified, in the human leukocyte antigen (HLA) alleles, strong
      genetic factors that predispose to liver injury on exposure to any of several
      drugs. Although the genetic associations have provided mechanistic insights, none
      has been developed as a predictive test. Further work in this area, in
      combination with other "-omics" technologies, is needed to develop tests that are
      both clinically useful and cost-effective.

PMID- 22850602
TI  - New pharmacotherapy for hepatitis C.
AB  - Chronic hepatitis C infection remains a major global public health burden
      associated with substantial morbidity and mortality. Recent advances in antiviral
      therapy with the US Food and Drug Administration (FDA) approval of the oral
      protease inhibitors boceprevir and telaprevir introduce a new era of treatment
      for hepatitis C based on directly acting antiviral agents, which are associated
      with significant improvements in viral eradication rates in combination with
      pegylated interferon plus ribavirin. Newer classes targeting the hepatitis C
      virus (HCV) protease, polymerase, NS5A, and other components of the viral genome
      demonstrate great promise to further enhance viral eradication with superior
      efficacy, improved tolerability, shorter duration of therapy, and diminished
      requirement for interferon. Current and future strategies for HCV pharmacotherapy
      are reviewed.

PMID- 22850603
TI  - Screening for problematic low back pain: STarT.

PMID- 22850605
TI  - A method to predict the ratio of the tracer conversion rate to the tracer back
      diffusion rate of an irreversible-type radiotracer in humans by preclinical
      evaluations.
AB  - OBJECTIVE: The aim of this study was to develop a method to predict a tracer's
      alpha-value in the human brain on the basis of animal data. The alpha-value is
      the ratio of the conversion rate and the back-diffusion rate (k3/k2) and is one
      of the critical kinetic features of the detection sensitivity of target molecule
      activity, such as enzyme activity, in the measurement of PET and single-photon
      emission computed tomography using an irreversible-type radiotracer. METHOD: The
      alpha-value in the rat brain was estimated by a simultaneous assay of the tracer
      uptake and the target biochemical activity using N-[C]-methylpiperidin-4-yl
      acetate ([C]MP4A) and N-[C]-methylpiperidin-4-yl propionate ([C]MP4P) as test
      tracers, both of which are metabolic trapping tracers for measurement of brain
      acetylcholinesterase. The alpha-value in humans was then extrapolated from the
      alpha-value in rats by considering the differences between the species. The
      predicted human alpha-values were compared with those obtained from the kinetic
      analyses of human PET studies using [C]MP4A and [C]MP4P. RESULT: The alpha-values
      in the human brain cortex were predicted to be 0.51+/-0.1 for MP4A and 0.25+/
      0.05 for MP4P. These results were close to values reported in other PET studies:
      0.48+/-0.1 to 0.73+/-0.2 for MP4A and 0.15+/-0.04 to 0.18+/-0.04 for MP4P.
      CONCLUSION: The alpha-value predicted by this method would be used for practical
      selection or development of irreversible-type radiotracers for human use.

PMID- 22850606
TI  - Impact of metoclopramide on image quality in myocardial perfusion imaging.
AB  - BACKGROUND: The effectiveness of metoclopramide in reducing gastrointestinal
      induced artifacts in myocardial perfusion imaging (MPI) is a subject of debate.
      We examined the significance of this pharmacological intervention in the quality
      of images obtained from MPI studies. PATIENTS AND METHODS: A total of 211
      suspected or known cases with coronary artery disease routinely referred to our
      nuclear medicine department for MPI were randomly assigned to group A and group
      B. Group A (N=125) comprised patients who received 10 mg of metoclopramide orally
      after the injection of the radiotracer [technetium-99m-labeled methoxyisobutyl
      isonitril (99mTc-MIBI)] 1 h before image acquisition, and group B (N=86)
      comprised patients who did not receive any pharmacological intervention and were
      considered the control group. All the scans in each group were assessed in the
      rest phase of a routine 2-day protocol. The single-photon emission computerized
      tomography (SPECT) images were visually evaluated in terms of extracardiac
      activities and their effects on image quality by three nuclear medicine
      physicians, who were blinded to the details of the protocol. RESULTS: Of the 125
      patients who had received metoclopramide, 16 (13%) had nonacceptable, 72 (57.6%)
      had acceptable (interpretable), and 37 (29.6%) had good image quality. The image
      quality in group B was nonacceptable in 10 (11.23%), acceptable in 48 (50.23%),
      and good in 28 (33.56%) patients. The overall interobserver agreement was good
      (kappa: 0.6-0.9, P<0.05) among the three readers. CONCLUSION: There was no
      statistically significant difference in terms of MPI-SPECT image quality between
      patients who received metoclopramide and those in the control group.
      Metoclopramide, therefore, did not exert a remarkable effect on the quality of
      our MPI scans.

PMID- 22850607
TI  - Developing a unified imaging approach for neuroendocrine tumours with the
      evolution of PET-CT with 68Ga-labelled somatostatin analogues: could this be
      tailored according to specific clinical context and individual patient
      requirement?

PMID- 22850604
TI  - Structure and mechanism of purine-binding riboswitches.
AB  - A riboswitch is a non-protein coding sequence capable of directly binding a small
      molecule effector without the assistance of accessory proteins to regulate
      expression of the mRNA in which it is embedded. Currently, over 20 different
      classes of riboswitches have been validated in bacteria with the promise of many
      more to come, making them an important means of regulating the genome in the
      bacterial kingdom. Strikingly, half of the known riboswitches recognize effector
      compounds that contain a purine or related moiety. In the last decade,
      significant progress has been made to determine how riboswitches specifically
      recognize these compounds against the background of many other similar cellular
      metabolites and transduce this signal into a regulatory response. Of the known
      riboswitches, the purine family containing guanine, adenine and 2'-deoxyguanosine
      binding classes are the most extensively studied, serving as a simple and useful
      paradigm for understanding how these regulatory RNAs function. This review
      provides a comprehensive summary of the current state of knowledge regarding the
      structure and mechanism of these riboswitches, as well as insights into how they
      might be exploited as therapeutic targets and novel biosensors.

PMID- 22850608
TI  - Remote long-term registrations of sleep-wake rhythms, core body temperature and
      activity in marmoset monkeys.
AB  - Initial studies in the day active marmoset monkey (Callithrix jacchus) indicate
      that the sleep-wake cycle of these non-human primates resembles that of humans
      and therefore conceivably represent an appropriate model for human sleep. The
      methods currently employed for sleep studies in marmosets are limited. The
      objective of this study was to employ and validate the use of specific remote
      monitoring system technologies that enable accurate long-term recordings of sleep
      wake rhythms and the closely related rhythms of core body temperature (CBT) and
      locomotor activity in unrestrained group-housed marmosets. Additionally, a pilot
      sleep deprivation (SD) study was performed to test the recording systems in an
      applied experimental setup. Our results show that marmosets typically exhibit a
      monophasic sleep pattern with cyclical alternations between NREM and REM sleep.
      CBT displays a pronounced daily rhythm and locomotor activity is primarily
      restricted to the light phase. SD caused an immediate increase in NREM sleep time
      and EEG slow-wave activity as well as a delayed REM sleep rebound that did not
      fully compensate for REM sleep that had been lost during SD. In conclusion, the
      combination of two innovative technical approaches allows for simultaneous
      measurements of CBT, sleep cycles and activity in multiple subjects. The
      employment of these systems represents a significant refinement in terms of
      animal welfare and will enable many future applications and longitudinal studies
      of circadian rhythms in marmosets.

PMID- 22850609
TI  - Evolution of three Pyrenophora cereal pathogens: recent divergence, speciation
      and evolution of non-coding DNA.
AB  - Three of the most important fungal pathogens of cereals are Pyrenophora tritici
      repentis, the cause of tan spot on wheat, and Pyrenophora teres f. teres and
      Pyrenophora teres f. maculata, the cause of spot form and net form of net blotch
      on barley, respectively. Orthologous intergenic regions were used to examine the
      genetic relationships and divergence times between these pathogens. Mean
      divergence times were calculated at 519 kya (+/-30) between P. teresf. teres and
      P. teresf. maculata, while P. tritici-repentis diverged from both Pyrenophora
      teresforms 8.04 Mya (+/-138 ky). Individual intergenic regions showed a
      consistent pattern of co-divergence of the P. teresforms from P. tritici
      repentis, with the pattern supported by phylogenetic analysis of conserved genes.
      Differences in calculated divergence times between individual intergenic regions
      suggested that they are not entirely under neutral selection, a phenomenon shared
      with higher Eukaryotes. P. tritici-repentis regions varied in divergence time
      approximately 5-12 Mya from the P. teres lineage, compared to the separation of
      wheat and barley some 12 Mya, while the P. teresf. teres and P. teresf. maculata
      intergenic region divergences correspond to the middle Pleistocene. The data
      suggest there is no correlation between the divergence of these pathogens the
      domestication of wheat and barley, and show P. teresf. teres and P. teresf.
      maculata are closely related but autonomous. The results are discussed in the
      context of speciation and the evolution of intergenic regions.

PMID- 22850610
TI  - Changes in advanced oxidation protein products, advanced glycation end products,
      and s-nitrosylated proteins, in patients affected by polycythemia vera and
      essential thrombocythemia.
AB  - OBJECTIVES: Oxidative stress has a clear pro tumoral effect in myeloproliferative
      neoplasms (MPDs). In this study, we analyzed oxidative stress in patients with
      essential thrombocythemia (ET) and polycythemia vera (PV). Design and methods We
      analyzed serum levels of advanced oxidation protein products (AOPPs) degradation,
      advanced glycation end products (AGEs), and protein nitrosylation in ET and PV
      patients. We also evaluated neutrophil gelatinase-associated lipocalin (NGAL)
      levels, an acute phase protein isolated in human neutrophils, the activation
      status of platelets and leukocytes, and the JAK2 (V617F) mutation status.
      RESULTS: AOPPs and s-nitrosylated proteins were significantly higher in PV and ET
      subjects as compared to healthy volunteers, while AGEs were higher in ET subjects
      with respect to controls. Moreover, in PV patients we found a correlation between
      s-nitrosylated proteins and Hb value. In ET patients AGEs were significantly
      higher in patients with thrombosis compared with those without thrombotic events.
      CONCLUSIONS: Our results suggest that oxidative stress could play a role in the
      physiopathology of MPDs and in the onset of myeloproliferative associated
      thrombotic risk.

PMID- 22850611
TI  - Serum carotenoids in relation to risk factors for development of atherosclerosis.
AB  - OBJECTIVE: To explore associations between serum carotenoids and risk factors for
      development of atherosclerosis. DESIGN AND METHODS: We studied 40 early
      atherosclerosis patients without clinical cardiovascular events and comparable
      healthy controls aged 45-68 years. Intima-media thickness (IMT) and arterial
      stiffness were simultaneously measured by carotid ultrasonography, and serum
      carotenoids and cytokines were determined by high-pressure liquid chromatograph
      (HPLC) and ELISA kits respectively. We evaluated the associations between serum
      carotenoids, early atherosclerosis and serum cytokines. RESULTS: Serum
      concentrations of lutein and zeaxanthin in early atherosclerosis patients were
      significantly lower than those of control subjects. PCA logistic analysis found
      that serum carotenoids were associated with decreased risk of atherosclerosis. In
      contrast, blood pressure, body mass index and serum triglyceride were positively
      related to the risk of atherosclerosis. Ridge regression analysis revealed that
      serum carotenoids were associated with inflammatory cytokines and apoE. More
      specifically, serum lutein was inversely associated with IL-6 (P<0.001) and
      positively associated IFN-gamma (P=0.002). In contrast, zeaxanthin had a
      significant negative association with VCAM-1 (P=0.001) and apoE (P=0.022)
      .Lycopene was inversely associated with VCAM-1(P=0.011) and LDL (P=0.046).
      CONCLUSIONS: The results suggested that early atherosclerosis patients had lower
      serum concentrations of lutein and zeaxanthin than healthy subjects. Serum
      carotenoids were associated with reduced risk of atherosclerosis. The
      associations between serum carotenoids and inflammatory cytokines may help to
      explain the possible protective effects of carotenoids on atherosclerosis.

PMID- 22850612
TI  - Urinary angiotensinogen as a novel early biomarker of intrarenal renin
      angiotensin system activation in experimental type 1 diabetes.
AB  - Urinary excretion of albumin (UAlb) is used clinically as a marker of diabetic
      nephropathy (DN). Although DN was thought to be a unidirectional process, recent
      studies demonstrated that a large proportion of patients diagnosed with DN
      reverted to normoalbuminuria. Moreover, despite the normoalbuminuria, one-third
      of them exhibited reduced renal function even during the microalbuminuric stage.
      This study was performed to investigate whether urinary angiotensinogen (UAGT)
      level may serve as a useful marker of the early stage of experimental type 1
      diabetes (T1DM). T1DM was induced by a single intraperitoneal injection of
      streptozotocin. Control mice were injected with citrate buffer. Two days after
      streptozotocin injection, half of the mice received continuous insulin treatment.
      Our data showed that UAlb excretion was increased 6 days after streptozotocin
      injection compared to controls, whereas UAGT excretion was increased at an
      earlier time point. These increases were reversed by insulin treatment. The UAGT
      to UAlb ratio was increased in diabetic mice compared to control mice.
      Furthermore, the increased AGT expression in the kidneys was observed in diabetic
      mice. These data suggest that UAGT might be useful as a novel early biomarker of
      activation of the renin-angiotensin system in experimental type 1 diabetes.

PMID- 22850613
TI  - Pharmacological stimulation of type 5 adenylyl cyclase stabilizes heart rate
      under both microgravity and hypergravity induced by parabolic flight.
AB  - We previously demonstrated that type 5 adenylyl cyclase (AC5) functions in
      autonomic regulation in the heart. Based on that work, we hypothesized that
      pharmacological modulation of AC5 activity could regulate the autonomic control
      of the heart rate under micro- and hypergravity. To test this hypothesis, we
      selected the approach of activating AC5 activity in mice with a selective AC5
      activator (NKH477) or inhibitor (vidarabine) and examining heart rate variability
      during parabolic flight. The standard deviation of normal R-R intervals, a marker
      of total autonomic variability, was significantly greater under micro- and
      hypergravity in the vidarabine group, while there were no significant changes in
      the NKH477 group, suggesting that autonomic regulation was unstable in the
      vidarabine group. The ratio of low frequency and high frequency (HF) in heart
      rate variability analysis, a marker of sympathetic activity, became significantly
      decreased under micro- and hypergravity in the NKH477 group, while there was no
      such decrease in the vidarabine group. Normalized HF, a marker of parasympathetic
      activity, became significantly greater under micro- and hypergravity in the
      NKH477 group. In contrast, there was no such increase in the vidarabine group.
      This study is the first to indicate that pharmacological modulation of AC5
      activity under micro- and hypergravity could be useful to regulate the autonomic
      control of the heart rate.

PMID- 22850614
TI  - Establishment of stable cell lines with high expression of heterodimers of human
      4F2hc and human amino acid transporter LAT1 or LAT2 and delineation of their
      differential interaction with alpha-alkyl moieties.
AB  - System L is a major transport system for cellular uptake of neutral amino acids.
      Among system L transporters, L-type amino acid transporter 1 (LAT1) is
      responsible for the nutrient uptake in cancer cells, whereas L-type amino acid
      transporter 2 (LAT2) is a transporter for non-cancer cells. In this study, we
      have established HEK293 cell lines stably expressing high levels of human LAT1
      and LAT2 forming heterodimers with native human 4F2hc of the cells. We have found
      that L-[(14)C]alanine is an appropriate substrate to examine the function of
      LAT2, whereas L-[(14)C]leucine is used for LAT1. By using L-[(14)C]alanine on
      LAT2, we have for the first time directly evaluated the function of human LAT2
      expressed in mammalian cells and obtained its reliable kinetics. Using alpha
      alkyl amino acids including alpha-methyl-alanine and alpha-ethyl-L-alanine, we
      have demonstrated that alpha-alkyl groups interfere with the interaction with
      LAT2. These cell lines with higher practical advantages would be useful for
      screening and analyzing compounds to develop LAT1-specific drugs that can be used
      for cancer diagnosis and therapeutics. The strategy that we took to establish the
      cell lines would also be applicable to the other heterodimeric transporters with
      important therapeutic implications.

PMID- 22850615
TI  - Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide
      induced inflammatory bone loss in an experimental model for periodontitis.
AB  - Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and
      maintains bone mass in estrogen-deficient ovariectomized mice. This study
      examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on
      lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin
      suppressed LPS-induced osteoclast formation and bone resorption and suppressed
      the receptor activator of NFkappaB ligand-induced osteoclastogenesis in RAW264.7
      macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse
      experimental model for periodontitis by inhibiting LPS-induced bone resorption.
      PMFs may therefore provide a new therapeutic approach for periodontal bone loss.

PMID- 22850616
TI  - Reductive functionalization of carbon dioxide to methyl acrylate at zerovalent
      tungsten.
AB  - Alkali metal reduction of tungsten tetrachloride in the presence of excess
      trimethylphosphite and ethylene affords moderate yields of trans
      tetrakis(trimethylphosphite)tungsten bis(ethylene). This easily prepared species
      bearing inexpensive ancillary ligands promotes the oxidative coupling of carbon
      dioxide and ethylene at ambient temperature to produce two isomeric
      tetrakis(trimethylphosphite)tungsten acrylate hydride complexes. These isomers
      vary by the kappa(2)-O,O and kappa(3)-C,C,O coordination mode of the acrylate
      ligand, and swiftly interconvert in solution as detected by 2D NMR spectroscopy.
      The CO(2)-derived acrylate fragment may be released from the tungsten
      coordination sphere by treatment with methyl iodide to afford modest quantities
      of free methyl acrylate.

PMID- 22850617
TI  - Quantification of Epstein-Barr virus DNA is helpful for evaluation of chronic
      active Epstein-Barr virus infection.
AB  - Chronic active Epstein-Barr virus infection (CAEBV) presents with chronic or
      recurrent infectious mononucleosis-like symptoms, such as low-grade fever, liver
      dysfunction, lymphadenopathy, and hepatosplenomegaly. Immunological methods are
      useful for the diagnosis of viral infections. However, CAEBV patients do not
      necessarily have high titers of Epstein-Barr virus (EBV)-specific antibodies.
      Hosts that are immunocompromised after hematopoietic stem cell transplantations
      sometimes suffer from systemic EBV-associated hemophagocytic lymphohistiocytosis
      (EBV-HLH) and EBV-positive lymphoma. Patients with EBV-associated diseases are
      often diagnosed by analyses of bone marrow. Cytomegalovirus (CMV) can cause
      serious pneumonia or retinitis in immunocompromised hosts. In order to
      noninvasively understand the clinical status of patients with EBV-associated
      diseases, we conducted real-time polymerase chain reaction (PCR) methods in their
      peripheral blood in order to quantify EBV and CMV DNA levels, which reflect viral
      activity. Here, we describe a 30-year-old Japanese female patient with CAEBV. The
      patient had repeated fever, fatigue, and liver dysfunction. The histopathological
      results of liver biopsies were positive for EBV-encoded RNA-1. Acute hepatitis
      was associated with the EBV infection. The whole-blood EBV DNA levels were high
      and above 1.0 * 107 copies/mL. After immunosuppressive and antiviral therapies,
      EBV DNA levels lowered. However, she had to receive bone marrow transplantation
      because of her EBV-HLH. As the number of lymphocytes increased in the post
      transplantation period, EBV DNA levels gradually increased again. The
      simultaneous detection of CMV DNA was more sensitive than the CMV antigenemia
      test that is often used to diagnose CMV infections. Unfortunately, the patient
      died due to a fungal infection. Observing EBV DNA levels closely with real-time
      quantitative PCR methods is helpful for evaluating the changes in the clinical
      course.

PMID- 22850618
TI  - Children's knowledge of hierarchical phrase structure: quantifier floating in
      Japanese.
AB  - The interpretation of floating quantifiers in Japanese requires knowledge of
      hierarchical phrase structure. However, the input to children is insufficient or
      even misleading, as our analysis indicates. This presents an intriguing question
      on learnability: do children interpret floating quantifiers based on a structure
      dependent rule which is not obvious in the input or do they employ a sentence
      comprehension strategy based on the available input? Two experiments examined
      four- to six-year-old Japanese-speaking children for their interpretations of
      floating quantifiers in SOV and OSV sentences. The results revealed that no child
      employed a comprehension strategy in terms of the linear ordering of
      constituents, and most five- and six-year-olds correctly interpreted floating
      quantifiers when word-order difficulty was reduced. These facts indicate that
      children's interpretation of floating quantifiers is structurally dependent on
      hierarchical phrase structure, suggesting that this knowledge is a part of
      children's grammar despite the insufficient input available to them.

PMID- 22850619
TI  - Selective sensitization of tumors to chemotherapy by marine-derived lipids: a
      review.
AB  - Despite great improvements, a significant proportion of cancer patients still
      die, mainly because of the development of metastases. At this stage, current
      treatments still rely heavily on conventional chemotherapy for most cancers. The
      efficacy of chemotherapy is dose-dependent, which is limited by toxicity to non
      tumor tissues, as a result of its poor tumor selectivity. To improve survival
      length and preserve quality of life, the challenge is to develop approaches aimed
      at increasing chemotherapy toxicity to tumor tissue while not affecting non-tumor
      tissues. Marine-derived lipids, docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA), have the potential to differentially sensitize tissues to
      chemotherapy. These lipids enhance the cytotoxicity of 15 anticancer drugs
      (antimetabolites, alkylating or intercalating agents, microtubule stabilizers,
      Abl tyrosine kinase inhibitor and arsenic trioxide) to a variety of cancer cell
      lines or tumors in animals, used as models for breast, prostate, colonic, lung,
      cervical, ovarian cancers, neuroblastomas, leukemia or lymphomas. However, DHA
      and EPA do not sensitize non-tumor tissues to anticancer drugs, which suggests
      that the effect of these lipids is tumor selective. Two phase II clinical trials
      already support these results, and randomized, phase III trials are ongoing. In
      this review, we discuss the double-faceted properties of these lipids, and then
      focus on their potential for transfer to the patient in the light of current
      therapeutic strategies. Should their beneficial effects be confirmed, the
      consequences could be considerable by opening up the prospect of systematic
      supplementation during cancer treatment, a significant shift in current cancer
      therapeutic paradigms.

PMID- 22850620
TI  - Direct correlation between work function of indium-tin-oxide electrodes and solar
      cell performance influenced by ultraviolet irradiation and air exposure.
AB  - We report on reversible changes of the work function (WF) values of indium-tin
      oxide (ITO) under prolonged ultraviolet (UV) and air exposure. The WF of ITO is
      reduced from 4.7 eV to 4.2 eV by photon absorption in ITO under UV illumination
      or an air mass 1.5 solar simulator (100 mW cm(-2)). Air or oxygen exposure is
      found to increase the WF of ITO (UV-exposed) to a value of 4.6 eV. These changes
      of ITO's WF lead to reversible variations of the performance of organic
      photovoltaic devices where ITO acts primarily as the electron collecting or hole
      collecting electrode. These variations can be reflected in the disappearance (or
      appearance) of an S-shaped kink in the J-V characteristics upon continuous UV or
      solar simulator illumination (or air exposure). This reversible phenomenon is
      ascribed to the adsorption and desorption of oxygen on the surface and grain
      boundaries of ITO. The use of surface modifiers to either decrease or increase
      the WF of ITO in organic photovoltaic devices with inverted and conventional
      geometries is also shown to be an effective route to stabilize the device
      performance under UV illumination.

PMID- 22850621
TI  - Management strategy for multifocal branch duct intraductal papillary mucinous
      neoplasms of the pancreas.
AB  - OBJECTIVES: Branch duct intraductal papillary mucinous neoplasms of the pancreas
      (BD-IPMNs) often are composed of multifocal lesions. We aimed to clarify the
      clinicopathologic features of multifocal BD-IPMNs. METHODS: Medical records of
      211 patients with BD-IPMNs (169 solitary and 42 multifocal) were retrospectively
      analyzed. We compared the pathological grade of resected IPMNs and the resulting
      clinical course between solitary and multifocal BD-IPMNs. RESULTS: Sixty-nine
      patients (54 with solitary and 15 with multifocal BD-IPMNs) underwent
      pancreatectomy, and of these patients, 62 exhibited at least 1 malignant
      predictor. There was no significant difference in the prevalence of malignancy in
      the resected BD-IPMNs between the 2 groups. In the remaining 142 patients who
      exhibited no malignant predictors, both groups demonstrated no differences in
      morphologic changes of BD-IPMNs. Seventeen distinct ductal carcinomas were
      identified in both groups, and there was no difference in the prevalence of
      ductal carcinoma between the 2 groups. Moreover, there was no significant
      difference in the disease-specific survival rate between the 2 groups.
      CONCLUSIONS: In patients with multifocal BD-IPMNs, resection is only warranted
      for lesions that exhibit malignancy predictors; moreover, closer attention to the
      potential presence or development of distinct ductal carcinoma in patients with
      multifocal and solitary BD-IPMNs is warranted.

PMID- 22850622
TI  - Expression of microRNAs in patients with pancreatic cancer and its prognostic
      significance.
AB  - OBJECTIVES: Investigation of expression profile of well-established microRNAs in
      pancreatic adenocarcinoma, and its correlation with clinicopathological factors.
      METHODS: Eighty-eight samples of ductal pancreatic adenocarcinoma and 98 control
      samples were analyzed by real-time polymerase chain reaction for miR-21, miR-31,
      miR-122, miR-145, miR-146a, miR-155, miR-210, and miR-222 expressions. The
      results were normalized and then statistically analyzed using nonparametric
      statistical tests. RESULTS: According to our results, miR-21, miR-155, miR-210,
      miR-221, and miR-222, were overexpressed in diseased tissues than in the control
      samples, whereas miR-31, miR-122, miR-145, and miR-146a were underexpressed.
      Additionally, the expressions of miR-21 and miR-155 were associated with tumor
      stage and poor prognosis. CONCLUSIONS: The tumorigenic role of miR-21 and miR-155
      was confirmed, whereas down-regulation of miR-31, miR-145, and miR-146a, in
      dispute with current literature, renders necessary the revision of use of
      microRNAs as biological markers.

PMID- 22850623
TI  - Anti-inflammatory role of cannabidiol and O-1602 in cerulein-induced acute
      pancreatitis in mice.
AB  - OBJECTIVES: The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the
      ligands of G protein-coupled receptor 55 (GPR55), on experimental acute
      pancreatitis (AP) were investigated. METHODS: Acute pancreatitis was induced in
      C57BL mice by intraperitoneal injection of 50 MUg/kg cerulein hourly, with a
      total of 6 times. Drugs (O-1602, 10 mg/kg, or CBD, 0.5 mg/kg) were given by
      intraperitoneal injection 2 times at 30 minutes before the first injection and
      immediately before the fifth cerulein injection. At 3 hours after the last
      injection, the blood, the lungs, and the pancreas were harvested for the
      pancreatic enzyme activity, myeloperoxidase activity, and pro-inflammatory
      cytokines measurement; and the expressions of GPR55 mRNA and protein in the
      pancreas were detected. RESULTS: Cannabidiol or O-1602 treatment significantly
      improved the pathological changes of mice with AP and decreased the enzyme
      activities, IL-6 and tumor necrosis factor alpha; levels, and the myeloperoxidase
      activities in plasma and in the organ tissues. G protein-coupled receptor 55 mRNA
      and protein expressed in the pancreatic tissue, and the expressions were
      decreased in the mice with AP, and either CBD or O-1602 attenuated these changes
      to a certain extent. CONCLUSION: Cannabidiol and O-1602 showed anti-inflammatory
      effects in mice with AP and improved the expression of GPR55 in the pancreatic
      tissue as well.

PMID- 22850624
TI  - Incidence, prognosis, and possible treatment strategies of peritoneal
      carcinomatosis of pancreatic origin: a population-based study.
AB  - OBJECTIVES: Peritoneal carcinomatosis (PC) is an important cause of morbidity and
      mortality among patients with pancreatic cancer. In an era where therapeutic
      options for PC of multiple origins are emerging, our aim was to provide
      population-based data on incidence, treatment, and prognosis of PC of pancreatic
      origin. METHODS: All patients with a condition diagnosed as nonendocrine
      pancreatic cancer between 1995 and 2009 in the area of the Eindhoven Cancer
      Registry were included. RESULTS: In total, 2924 patients had a diagnosis of
      pancreatic cancer of which 265 patients (9%) presented with synchronous PC. An
      increasing trend could be noted in patients treated with chemotherapy in more
      recent years (11% in 1995-1999 and 22% in 2005-2009; P = 0.060). Median survival
      in patients presenting with PC was only 6 weeks (95% confidence interval, 5-7
      weeks) and did not improve over time, contrasting improvements among patients
      with nonmetastasized disease (19-30 weeks) and patients with metastasized disease
      confined to the liver (8-12 weeks). CONCLUSION: Prognosis of patients with
      pancreatic cancer presenting with PC remains extremely poor. Treatment options
      are scarce and, given the magnitude of the problem, efforts should be undertaken
      to develop effective treatments in experimental and clinical studies.

PMID- 22850625
TI  - Noggin attenuates cerulein-induced acute pancreatitis and impaired autophagy.
AB  - OBJECTIVES: To investigate the role of bone morphogenetic protein (BMP) signaling
      in acute pancreatitis (AP) by administration of noggin, an endogenous BMP
      antagonist, in a cerulein-induced AP model. METHODS: Acute pancreatitis was
      induced by 9 hourly intraperitoneal injections of cerulein (50 MUg/kg). Control
      mice received phosphate-buffered saline injections. In a separate group, noggin
      (0.5 mg/kg) was given intraperitoneally at 1 hour before and 2, 4, and 6 hours
      after AP induction. The mice were euthanized at 1 hour after completion of AP
      induction. The blood samples and the pancreas were harvested for analysis.
      Isolated pancreatic acini from normal mice and AR42J cells were treated with BMP2
      and cerulein. AR42J cells were also treated with noggin. Phosphorylation of
      Smad1/5/8 was measured. RESULTS: Bone morphogenetic protein signaling was up
      regulated in AP mouse pancreas. Bone morphogenetic protein 2 and cerulein-induced
      phosphorylation of Smad1/5/8 in the acinar cells in vitro, which was blocked by
      noggin. Noggin administration in vivo attenuated AP induction, decreased vacuole
      formation in acinar cells, blocked LC3-II levels, and partially restored Beclin-1
      and lysosomal-associated membrane protein 2 levels. CONCLUSIONS: Bone
      morphogenetic protein signaling seems to promote AP induction and autophagy, as
      suggested by our study showing that noggin ameliorates AP and partially restores
      autophagic homeostasis.

PMID- 22850626
TI  - Longitudinal health-related quality of life assessment implications for prognosis
      in stage IV pancreatic cancer.
AB  - OBJECTIVES: We investigated whether changes in quality of life (QoL) during
      treatment could predict survival in stage IV pancreatic cancer. METHODS: Quality
      of life was evaluated at baseline and after 3 months of treatment using European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ-C30) in 186 patients with stage IV pancreatic cancer. Cox regression
      evaluated the prognostic significance of baseline and changes in QoL scores after
      adjusting for age, sex, and treatment history. RESULTS: One hundred twenty-one
      patients were males and 65 were females. One hundred twenty-seven patients'
      condition was newly diagnosed, whereas 59 were previously treated. The mean age
      at diagnosis was 55.1 years. Baseline QoL scale predictive of survival upon
      multivariate analysis was global health (hazard ratio, 0.88; 95% confidence
      interval, 0.81-0.95; P = 0.001). On multivariate analysis, QoL change variable
      that was significantly predictive of survival after 3 months of treatment was
      cognitive function (hazard ratio, 0.89; 95% confidence interval, 0.79-0.99; P =
      0.04). CONCLUSIONS: This study provides preliminary evidence to indicate that
      patients with stage IV pancreatic cancer who have a better global health at
      baseline as well as those whose cognitive function improves within 3 months of
      treatment have a significantly increased probability of survival.

PMID- 22850629
TI  - Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts:
      associations and gene-environment interactions with childhood/adolescent physical
      assault.
AB  - The complex etiology of suicidal behavior has frequently been investigated in
      relation to monoaminergic neurotransmission, but other neurosystems have shown
      alterations as well, involving excitatory glutamatergic and inhibitory gamma
      aminobutyric acid (GABA) molecular components, together with the modulating
      polyamines. Sufficiently powered and family-based association studies of
      glutamatergic and GABAergic genes with suicidal behavior are nonexistent, but
      several studies have been reported for polyamines. We therefore conducted, for
      the first time ever, an extensive family-based study of 113 candidate single
      nucleotide polymorphisms (SNPs) located in 24 glutamatergic and GABA genes, in
      addition to interrelated polyaminergic genes, on the outcome of severe suicide
      attempts (SAs). The family-based analysis (n=660 trios) was supplemented with
      gene-environment interaction (G * E), case-control (n=519 controls) and subgroup
      analyses. The main observations were the previously unreported association and
      linkage of SNPs rs2268115 and rs220557 in GRIN2B, as well as of SNPs rs1049500
      and rs2302614 in ODC1 (P<10(-2)). Furthermore, GRIN2B haplotypic associations
      were observed, in particular with a four-SNP AGGC haplotype (rs1805247-rs1806201
      rs1805482-rs2268115; P<10(-5)), and a third SNP rs7559979 in ODC1 showed G * E
      with serious childhood/adolescent physical assault (P<10(-4)). SA subjects were
      characterized by transdiagnostic trait anger and past year alcohol-drug use
      disorders, but not by alcohol-drug use at SA, depression, anxiety or psychosis
      diagnoses. We also discuss a first ever confirmatory observation of SNP rs6526342
      (polyaminergic SAT1) in SA, originally identified in completed suicides. The
      results suggest that specific genetic variants in a subset of glutamatergic
      (GRIN2B) and polyaminergic (ODC1) neurosystem genes may be of importance in
      certain suicidal subjects. 

PMID- 22850627
TI  - Latrepirdine improves cognition and arrests progression of neuropathology in an
      Alzheimer's mouse model.
AB  - Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has
      yielded mixed results in clinical trials of mild to moderate Alzheimer's disease,
      with a dramatically positive outcome in a Russian clinical trial that was
      unconfirmed in a replication trial in the United States. We sought to determine
      whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism
      is at least partially attributable to regulation of macroautophagy, a highly
      conserved protein catabolism pathway that is known to be impaired in brains of
      patients with Alzheimer's disease (AD). We utilized several mammalian cellular
      models to determine whether LAT regulates mammalian target of rapamycin (mTOR)
      and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT
      prior to behavior analysis in the cued and contextual fear conditioning paradigm,
      as well as immunohistological and biochemical analysis of AD-related
      neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced
      mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic
      mice was associated with improved learning behavior and with a reduction in
      accumulation of Abeta42 and alpha-synuclein. We conclude that LAT possesses pro
      autophagic properties in addition to the previously reported pro-neurogenic
      properties, both of which are potentially relevant to the treatment and/or
      prevention of neurodegenerative diseases. We suggest that elucidation of the
      molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and
      behavior might warranty the further study of LAT as a potentially viable lead
      compound that might yield more consistent clinical benefit following the
      optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive
      activities. 

PMID- 22850628
TI  - Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant
      associated with bipolar disorder.
AB  - Several genome-wide association studies for bipolar disorder (BD) have found a
      strong association of the Ankyrin 3 (ANK3) gene. This association spans numerous
      linked single-nucleotide polymorphisms (SNPs) in an ~250-kb genomic region
      overlapping ANK3. The associated region encompasses predicted regulatory elements
      as well as two of the six validated alternative first exons, which encode
      distinct protein domains at the N-terminus of the protein also known as Ankyrin
      G. Using RNA ligase-mediated rapid amplification of cDNA ends to identify novel
      transcripts in conjunction with a highly sensitive, exon-specific multiplexed
      mRNA expression assay, we detected differential regulation of distinct ANK3
      transcription start sites and coupling of specific 5' ends with 3' mRNA splicing
      events in postmortem human brain and human stem cell-derived neural progenitors
      and neurons. Furthermore, allelic variation at the BD-associated SNP rs1938526
      correlated with a significant difference in cerebellar expression of a brain
      specific ANK3 transcript. These findings suggest a brain-specific cis-regulatory
      transcriptional effect of ANK3 that may be relevant to BD pathophysiology.

PMID- 22850630
TI  - A nitroolefin functionalized BODIPY chemodosimeter for biothiols driven by an
      unexpected conjugated addition mechanism.
AB  - A weakly fluorescent nitroolefin functionalized BODIPY 1 was prepared and rapidly
      reacted with thiols through an unexpected conjugated addition to the azafulvene
      ring of BODIPY to generate highly fluorescent BODIPYs 4 and 5. This reaction was
      applied for the highly selective and sensitive detection of Cys in living cells.

PMID- 22850631
TI  - The importance of E-cadherin binding partners to evaluate the pathogenicity of E
      cadherin missense mutations associated to HDGC.
AB  - In hereditary diffuse gastric cancer (HDGC), CDH1 germline gene alterations are
      causative events in 30% of the cases. In 20% of HDGC families, CDH1 germline
      mutations are of the missense type and the mutation carriers constitute a problem
      in terms of genetic counseling and surveillance. To access the pathogenic
      relevance of missense mutations, we have previously developed an in vitro method
      to functionally characterize them. Pathogenic E-cadherin missense mutants fail to
      aggregate and become more invasive, in comparison with cells expressing the wild
      type (WT) protein. Herein, our aim was to develop a complementary method to
      unravel the pathogenic significance of E-cadherin missense mutations. We used
      cells stably expressing WT E-cadherin and seven HDGC-associated mutations (five
      intracellular and two extracellular) and studied by proximity ligation assays
      (PLA) how these mutants bind to fundamental regulators of E-cadherin function and
      trafficking. We focused our attention on the interaction with: p120, beta
      catenin, PIPKIgamma and Hakai. We showed that cytoplasmic E-cadherin mutations
      affect the interaction of one or more binding partners, compromising the E
      cadherin stability at the plasma membrane and likely affecting the adhesion
      complex competence. In the present work, we demonstrated that the study of the
      interplay between E-cadherin and its binding partners, using PLA, is an easy,
      rapid, quantitative and highly reproducible technique that can be applied in
      routine labs to verify the pathogenicity of E-cadherin missense mutants for HDGC
      diagnosis, especially those located in the intracellular domain of the protein.

PMID- 22850632
TI  - Protective effect of methotrexate in patients with rheumatoid arthritis and
      cardiovascular comorbidity.
AB  - Rheumatoid arthritis (RA) is associated with an increased risk of premature
      mortality, predominantly due to increased cardiovascular disease (CVD). Systemic
      inflammation has been established as one of the primary drivers of accelerated
      atherosclerosis in RA, though other traditional and disease-specific risk factors
      also contribute. There is evidence that methotrexate, considered a mainstay of
      therapy for RA, can ameliorate some of this excess CVD risk, an effect that has
      not been seen consistently with other disease-modifying antirheumatic drugs. The
      cardioprotective action of methotrexate may occur through reducing systemic
      inflammation and by directly affecting some of the cellular mechanisms that lead
      to atherosclerosis. On the basis of this evidence, there are ongoing trials of
      low-dose methotrexate in patients from the general population with CVD but who do
      not have RA. Methotrexate reduces the overall CVD burden in patients with RA.
      With earlier treatment of RA and earlier use of methotrexate it is possible that
      we may have the capability to radically change patients' long-term CVD risk.

PMID- 22850633
TI  - The practical application of chimerism analyses in allogeneic stem cell
      transplant recipients: blood chimerism is equivalent to marrow chimerism.
AB  - BACKGROUND: Chimerism defines the amount of donor versus recipient hematopoiesis
      following allogeneic stem cell transplant (SCT). PCR-based analyses of short
      tandem repeats (STRs) are commonly used and are accurate and applicable to
      allogeneic transplant recipients. These analyses are performed on blood and
      marrow aspirates, but it is unknown if analyses of both are required. We
      performed a retrospective analysis of 42 consecutive adult allogeneic SCT
      recipients at our institution to determine if both sample types are needed.
      METHODS: Chimerism status was determined by multiplex PCR and capillary
      electrophoresis of STRs. Analyses were performed at 30, 60, and 90days after SCT
      on both unfractionated blood and unfractionated marrow aspirate. RESULTS: PCR
      analyses of STRs for chimerism performed on unfractionated blood highly
      correlated with results obtained using unfractionated marrow aspirates at 30, 60,
      or 90days following transplant (p<0.0001 for each time point). Overall and
      relapse-free survival of patients experiencing full donor chimerism was not
      statistically different from patients demonstrating mixed chimerism at days 30,
      60, and 90 following SCT. CONCLUSIONS: PCR-based chimerism analyses on blood
      provide similar information as marrow aspirate analyses. These are unique results
      suggesting that chimerism analyses may be assessed on peripheral blood alone.

PMID- 22850634
TI  - Protective effects of N-(2-mercaptopropionyl)-glycine against ischemia
      reperfusion injury in hypertrophied hearts.
AB  - The beneficial effects of N-(2-mercaptopropionyl)-glycine (MPG) against ischemia
      reperfusion injury in normotensive animals have been previously studied. Our
      objective was to test the action of MPG during ischemia and reperfusion in hearts
      from spontaneously hypertensive rats (SHR). Isolated hearts from SHR and age
      matched normotensive rats Wistar Kyoto (WKY) were subjected to 50-min global
      ischemia (GI) and 2-hour reperfusion (R). In other hearts MPG 2mM was
      administered during 10 min before GI and the first 10 min of R. Infarct size (IS)
      was assessed by TTC staining technique and expressed as percentage of risk area.
      Postischemic recovery of myocardial function was assessed. Reduced glutathione
      (GSH), thiobarbituric acid reactive substances (TBARS) and SOD cytosolic activity
      - as estimators of oxidative stress and MnSOD cytosolic activity - as an index of
      (mPTP) opening were determined. In isolated mitochondria H(2)O(2)-induced mPTP
      opening was also measured. The treatment with MPG decreased infarct size,
      preserved GSH levels and decreased SOD and MnSOD cytosolic activities, TBARS
      concentration, and H(2)O(2) induced-mPTP opening in both rat strains. Our results
      show that in both hypertrophied and normal hearts an attenuation of mPTP opening
      via reduction of oxidative stress appears to be the predominant mechanism
      involved in the cardioprotection against reperfusion injury MPG-mediated.

PMID- 22850635
TI  - Synthesis of diamondoid lanthanide-polyoxometalate solids as tunable
      photoluminescent materials.
AB  - The reaction between polyoxometalate (POM)
      [TBA](12)[WZn{Zn(H(2)O)}(2)(ZnW(9)O(34))(2)] (TBA = tetrabutyl ammonium) and
      lanthanide (Ln) nitrate (Ln = La, Eu and Tb) in a mixed solvent of CH(3)CN and
      DMF yielded three noncentrosymmetric diamondoid Ln-POM solid materials,
      {[Ln(2)(DMF)(8)(H(2)O)(6)][ZnW(12)O(40)]}.4DMF (Ln-POM; Ln = La, Eu and Tb). In
      these compounds, the {ZnW(12)O(40)} unit, transferred from the metastable
      [WZn{Zn(H(2)O)}(2)(ZnW(9)O(34))(2)] cluster, acts as a tetradentate ligand to
      connect with four Ln nodes, while the Ln ion links up two {ZnW(12)O(40)} units.
      These compounds generated interesting luminescence emissions that are dependent
      on the Ln ions and their ratios. White light emission was obtained by a doped
      approach with a rational ratio of the Eu(3+) and Tb(3+) ions.

PMID- 22850636
TI  - Roles and applications of biomedical ontologies in experimental animal science.
AB  - A huge amount of experimental data from past studies has played a vital role in
      the development of new knowledge and technologies in biomedical science. The
      importance of computational technologies for the reuse of data, data integration,
      and knowledge discoveries has also increased, providing means of processing large
      amounts of data. In recent years, information technologies related to
      "ontologies" have played more significant roles in the standardization,
      integration, and knowledge representation of biomedical information. This review
      paper outlines the history of data integration in biomedical science and its
      recent trends in relation to the field of experimental animal science.

PMID- 22850637
TI  - Complex quantitative traits cracked by the mouse inter-subspecific consomic
      strains.
AB  - Mammalian quantitative traits that are observed at the whole-body level, such as
      body weight and length and blood biochemical parameters, are determined by the
      cooperative effects of multiple genetic and epigenetic factors as well as
      environmental factors. This complexity has hampered the genetic analysis of
      quantitative traits. To overcome this difficulty, we have established a full set
      of consomic mouse strains, also known as chromosome substitution strains, by
      replacing every chromosome of the classical inbred strain C57BL/6J with its
      counterpart from the Japanese wild-mouse-derived inbred strain MSM/Ms. The core
      components of the genomes of these two strains originated from different mouse
      subspecies. The inter-subspecific large-genome divergence and phenotypic
      differences between the two strains allowed the identification of genetic
      determinants for many quantitative traits by comprehensive phenotype screening.
      For some quantitative traits, the genetic determinants could be dissected into
      multiple chromosomes, thereby reflecting strain differences between C57BL/6J and
      MSM/Ms and their simple additive effects on the background of the consomic host
      strain. For other quantitative traits, the measured values of some consomic
      strains often far exceeded the range of the two parental strains, which suggests
      that nonadditive genetic interactions occur among multiple genes located on the
      substituted MSM/Ms chromosomes and the consomic host chromosomes. Thus, the inter
      subspecific consomic strains are unique tools that can be used to identify both
      additive and nonadditive genetic effects on quantitative complex traits.

PMID- 22850638
TI  - Experimental techniques for neuroscience research using common marmosets.
AB  - The common marmoset (Callithrix jacchus) is a species of New World monkeys.
      Because of its ease of maintenance and breeding in laboratories, use of the
      marmoset is growing rapidly in biomedical research. In neuroscience, the
      marmosets are attracting more attention, since they have the developed cerebral
      cortex which plays a key role in higher brain functions. In this review on
      neuroscience research using the marmoset, experimental techniques developed in
      our laboratory are summarized. We introduce artificial rearing of neonates,
      stereotaxic surgery, neuroanatomy including virtual microscopy based on the
      Internet technology, behavioral study using a large number of marmosets, and
      primary neuron culture study.

PMID- 22850639
TI  - Blood calcium levels in immature rats: influence of extracellular calcium
      concentration on myocardial calcium handling.
AB  - Calcium ions play an important role in several cell functions, from fertilization
      to cell death. The cytosolic Ca(2+) concentration is much lower than the
      extracellular concentration ([Ca(2+)](o)). The latter may markedly affect Ca(2+)
      fluxes across the cell membrane and thus the cellular Ca(2+) load. Thus, when
      working with preparations in vitro, it is important to keep [Ca(2+)](o) close to
      the in vivo value. In this study, we determined the calcemia in immature rats,
      for which values are currently unavailable, and investigated how
      supraphysiological [Ca(2+)](o) affects myocardial Ca(2+) handling. Blood ionized
      [Ca(2+)] was similar in neonatal (2-5 days old) and adults Wistar rats (1.28 +/-
      0.03 and 1.31 +/- 0.03 mmol/l; n=6 and 5, respectively, P>0.37), and lower than
      the [Ca(2+)](o) range often used in experiments with neonatal myocardial
      preparations. Cytosolic Ca(2+) transients, measured with indo-1 in neonatal
      ventricular myocytes, were enhanced by an increase in [Ca(2+)](o) from 1.2 to 2
      mM, which also increased the Ca(2+) content in the sarcoplasmic reticulum (SR),
      and changed the pattern of competition between the main transporters that remove
      Ca(2+) from the cytosol (SR Ca(2+)-ATPase and Na(+)/Ca(2+) exchanger). These
      observations stress the importance of using physiological [Ca(2+)](o) values for
      reliability of results. It is expected that the present calcemia data, reported
      for the first time in immature rats, may contribute to the refinement of in vitro
      experiments with neonatal rat preparations.

PMID- 22850640
TI  - Mucosal immune responses in W/W(v) and Sl/Sl(d) mutant mice.
AB  - In order to identify potential unanticipated side reactions and immune responses,
      the evaluation of candidate vaccines should include immunization of the murine
      model of the disease in question and mutant animals, as well as normal laboratory
      animals. We employed WBB6F(1)-W/W(v) and WBB6F(1)-Sl/Sl(d) mutant mice, which are
      genetically mast cell deficient and lack intestinal pacemaker activity due to a
      severe deficiency in interstitial cells of Cajal. Antigen-specific mucosal and
      systemic immune responses in the mutant and congenic normal mice were induced by
      intranasal or intragastric immunization with ovalbumin (OVA) plus cholera toxin
      as an adjuvant. It was found that the levels of the OVA-specific humoral immune
      response in the mucosal and systemic tissues of the mutant mice immunized
      intranasally were roughly equivalent to those of the congenic normal mice. In
      contrast, the specific humoral immune response in the intragastrically immunized
      mutant mice was greater than that observed in the congenic normal mice.
      Unexpectedly, the titers of OVA-specific IgA antibodies and total IgA antibodies
      in the fecal extracts of both intranasally and intragastrically immunized mutant
      mice were significantly lower than in those of the congenic normal mice. Although
      the detailed mechanisms leading to these differences remain unclear, the
      unexpected immune responses observed in the gastrointestinal tracts of the mice
      in this study may be related to an abnormality of gastrointestinal motility. Our
      data therefore suggest that studies using mutant mice and physiological
      assessments should be carried out during mucosal vaccine development.

PMID- 22850641
TI  - Establishment of an experimental mouse model of trauma-hemorrhagic shock.
AB  - This study established an experimental mouse model of trauma-hemorrhagic shock
      (THS). THS-induced mice (C57BL/6J, n=33) were subjected to femoral fracture,
      ischemia for 90 min, and resuscitation for 15 min. The sham-operated mice
      (C57BL/6J, n=33) underwent the same anesthetic and surgical procedures, but
      neither trauma-hemorrhage nor fluid resuscitation were performed. Mean arterial
      pressure (MAP) and microvascular tissue perfusion over the small intestine,
      liver, and left kidney were longitudinally measured in all mice. Blood was
      collected for analysis at baseline and 3, 6, 12, and 24 h post resuscitation, and
      the small intestine, liver, and left kidney were resected for hematoxylin and
      eosin staining 24 h post resuscitation. Compared with the sham group, MAP and
      microvascular tissue perfusion over the small intestine, liver, and left kidney
      were all significantly reduced in the THS group at the end of hemorrhage.
      Following resuscitation, no significant differences were observed between the
      groups. THS induction was associated with significantly increased plasma
      concentrations of Cr, AST, CPK, IL-6, IL-10, and TNF-alpha from the baseline
      values by two- to three-fold after the hemorrhage phase, and THS-induced mice
      demonstrated significantly increased histological injury scores. The rapid drop
      in MAP and microvascular tissue perfusion observed following THS induction, and
      the gradual recovery post resuscitation, reflects the successful establishment of
      a THS experimental mouse model.

PMID- 22850642
TI  - Bone marrow-engrafted cells after mice umbilical cord blood transplantation
      differentiate into osteoblastic cells in response to fracture and placement of
      titanium screws.
AB  - As the in vivo function of bone marrow-engrafted umbilical cord blood (UCB)
      derived mesenchymal cells (UCBCs) after UCB transplantation is unknown, we
      examined in vivo osteoblastic differentiation using mouse UCB transplantation and
      fracture models. UCBCs obtained from GFP transgenic mice were intravenously
      injected into irradiated C57BL/6 mice. After three months, the in vivo
      osteoblastic differentiation potential of bone marrow-engrafted UCBCs was
      examined histologically using a mouse fracture model. GFP-positive UCBCs were
      detected in the bone marrow of recipient mice. On day 7, UCBCs were observed in
      the fracture gap and surrounding the titanium screws of the fixation device. The
      UCBCs were also positive for alkaline phosphatase and von Kossa staining. By day
      14, UCBCs were observed around and within a formed intramedullary callus. The
      newly formed woven bone consisted of ALP- and von Kossa-positive cells. Our
      findings suggest that UCBCs contribute to the fracture healing process after bone
      marrow engraftment and that UCBC transplantation can fully reconstruct not only
      hematopoietic cells but also mesenchymal cell lineages.

PMID- 22850643
TI  - A novel Kit gene mutation in CF1 mice involved in the extracellular domain of the
      KIT protein.
AB  - We screened for natural mutations in Crl:CF1 closed colony mice using an ordinary
      backcrossing system. Five of 30 CF1 males carried novel genes that caused white
      spots on colored coats. Their backcross progenies showed a white spot phenotype.
      The white spot gene was mapped to approximately 39 cM on chromosome 5, where the
      Kit gene is known to reside. Allelism testing between this spot gene and the Kit
      gene was performed using two already known Kit alleles, Kit(W), and Kit(W-v). We
      demonstrated that the spot mutation was semidominant and a novel allele of the
      Kit gene, which was tentatively named Kit(W-Ham). No infertility or anemia was
      observed in Kit(W-Ham) homozygotes. However, a reduced number of germ cells and
      mast cells was observed in Kit(W-Ham)/Kit(W) and Kit(W-Ham)/Kit(W-v)
      transheterozygotes. Sequencing of the 21 exons of the Kit gene in the Kit(W-Ham)
      mutants revealed that a unique guanine-to-adenine (G-A) transition at nucleotide
      position 545 (c.545G>A) of exon 3 changes arginine (R) to glutamine (Q) at
      position 182 in the extracellular domain of the KIT protein (p.R182Q). This
      extracellular KIT domain is a binding site for stem cell factors (SCF). It was
      concluded that the Kit(W-Ham) mutant may serve as a new model of human
      piebaldism.

PMID- 22850644
TI  - Noninvasive monitoring of beta-cell mass and fetal beta-cell genesis in mice
      using bioluminescence imaging.
AB  - Bioluminescence imaging (BLI) has been applied in gene therapy and research to
      screen for transgene expression, progression of infection, tumor growth and
      metastasis, and transplantation. It enables real-time and relatively noninvasive
      localization and serial quantification of biological processes in experimental
      animals. In diabetes research, BLI has been employed for the quantification of
      beta-cell mass, monitoring of islet graft survival after transplantation, and
      detection of reporter gene expression. Here, we explore the use of BLI in a
      transgenic mouse expressing luciferase under the control of the mouse insulin 1
      promoter (MIP-Luc-VU). A previous report on MIP-Luc-VU mice showed luminescence
      intensities emitted from the islets correlated well with the number of islets in
      vitro and in vivo. In this study, we showed MIP-Luc-VU mice fed a high fat diet
      for 8 weeks gave rise to a greater bioluminescent signal than mice fed a regular
      diet for the same period of time. Conversely, there was a strong reduction in the
      signal observed in diabetic Mafa-deficient/Mafk-transgenic mutant mice and
      streptozotocin-treated mice, reflecting the loss of beta-cells. Furthermore, we
      were able to monitor fetal beta-cell genesis in MIP-Luc-VU mice during the late
      gestational stage in a noninvasive and repetitive manner. In summary, we show
      that bioluminescence imaging of mice expressing a beta-cell specific reporter
      allows detection of changes in beta-cell mass and visualization of fetal beta
      cell neogenesis in uteri.

PMID- 22850645
TI  - The effect of artificial rearing on gut microbiota in a mouse pup-in-a-cup model.
AB  - In this paper, the mouse pup-in-a-cup model was improved for younger mouse pups,
      and the effect of artificial rearing on gut microbiota development was evaluated.
      Intragastric cannulas were placed through the esophagus into 3-day-old C57BL/6J
      mice (n=48), and the mice were artificially reared (AR) with mouse milk
      substitute (MMS). Littermate pups (n=20) were maternally reared (MR) as controls.
      The feces of 3-day-old pups were analyzed by combining the PCR-denaturing
      gradient gel electrophoresis (DGGE) fingerprinting technique and sequencing of
      16s rRNA gene fragments. After 11 days of artificial rearing, 37 of 48 pups were
      still alive. There were no significant changes in the number of DGGE bands or the
      Shannon index between the two groups. However, several bands in the AR group were
      obviously different from those in the MR group in the DGGE profile. These results
      demonstrate that it is possible to implant intragastric cannulas into 3-day-old
      C57BL/6J mice pups. However, the variation in the gut microbiota composition is
      non-negligible, even though the AR pups grow well.

PMID- 22850646
TI  - Characteristics of Himalayan marmots and their response to an atherogenic diet.
AB  - The purpose of the present study was to characterize Himalayan marmot lipoprotein
      profiles and investigate their response to an atherogenic diet. Sixteen marmots
      were randomly divided into two groups. The control group was fed with a standard
      chow diet, and the other group was fed with a chow diet containing 0.3%
      cholesterol, 6.7% lard, and 3.3% corn oil (designated as HFCD) for 16 weeks. The
      plasma lipids were measured, and lipoprotein profiles were analyzed. With the
      chow diet, the major lipoproteins were high density lipoproteins. HFCD feeding
      increased not only plasma total cholesterol levels but also body weight compared
      with the control group (P<0.05). Plasma lipoprotein (a) was detected in marmots,
      and the plasma lipoprotein (a) levels were 4.5-fold higher after being fed HFCD
      for 16 weeks. However, atherosclerotic lesions were not found in the aorta of
      HFCD-fed marmots. This study suggested that marmots are HDL-rich mammals and
      resistant to HFCD-induced atherosclerosis.

PMID- 22850647
TI  - Data on Wistar Hannover rats from a general toxicity study.
AB  - The aim of this study was to collect data on chronological changes in clinical
      laboratory tests, pathological examinations, and hepatic drug-metabolizing
      enzymes from Wistar Hannover rats at 8, 10, 19, and 32 weeks of age. The serum
      triglyceride concentration and the serum LDL cholesterol level were higher in
      males than in females at all ages. In contrast, serum total protein and
      creatinine concentrations and cholinesterase activity were lower in males than in
      females. In addition, sex differences were confirmed in pituitary weight and
      hepatic CYP3A2 and CYP2C11 activities. In conclusion, the general toxicological
      data noted in clinical laboratory tests, pathological examinations, and hepatic
      drug-metabolizing enzymes relating to chronological changes and sex differences
      may be useful in assessing drug-related toxicity in this strain.

PMID- 22850648
TI  - The formation and stability of molybdenum-antimony and tungsten-antimony ternary
      oxides Sb2MO6, Sb2M2O9, Sb2Mo3O12 and Sb4MO9 in the gas phase (M = Mo, W).
      Quantum chemical and mass spectrometric studies.
AB  - The ternary oxides Sb(2)MO(6), Sb(2)M(2)O(9), Sb(4)MO(9) (M = Mo, W) and
      Sb(2)Mo(3)O(12) were detected in the gas phase by means of mass spectrometry
      (MS). These gaseous oxides are reported for the first time. Thermodynamic data
      was obtained experimentally and confirmed by quantum chemical (QC) calculations.
      In addition, structural data on these molecules was obtained. The ionisation
      potentials (IP) were also determined both experimentally and theoretically.

PMID- 22850649
TI  - Estimation of maximal oxygen uptake without exercise testing in Korean healthy
      adult workers.
AB  - Maximal oxygen uptake is generally accepted as the most valid and reliable index
      of cardiorespiratory fitness and functional aerobic capacity.  The exercise test
      for measuring maximal oxygen uptake is unsuitable for screening tests in public
      heath examinations, because of the potential risks of exercise exertion and time
      demands.  We designed this study to determine whether work-related physical
      activity is a potential predictor of maximal oxygen uptake, and to develop a
      maximal oxygen uptake equation using a non-exercise regression model for the
      cardiorespiratory fitness test in Korean adult workers.  Study subjects were
      adult workers of small-sized companies in Korea.  Subjects with history of
      disease such as hypertension, diabetes, asthma and angina were excluded.  In
      total, 217 adult subjects (113 men of 21-55 years old and 104 women of 20-64
      years old) were included.  Self-report questionnaire survey was conducted on
      study subjects, and maximal oxygen uptake of each subject was measured with the
      exercise test.  The statistical analysis was carried out to develop an equation
      for estimating maximal oxygen uptake.  The predictors for estimating maximal
      oxygen uptake included age, gender, body mass index, smoking, leisure-time
      physical activity and the factors representing work-related physical activity. 
      The work-related physical activity was identified to be a predictor of maximal
      oxygen uptake.  Moreover, the equation showed high validity according to the
      statistical analysis.  The equation for estimating maximal oxygen uptake
      developed in the present study could be used as a screening test for assessing
      cardiorespiratory fitness in Korean adult workers.

PMID- 22850650
TI  - Synthesis of 3,7-diiodo-2,6-di(thiophen-2-yl)benzo[1,2-b:4,5-b']difurans:
      functional building blocks for the design of new conjugated polymers.
AB  - 3,7-Diiodo-2,6-di(thiophen-2-yl)benzo[1,2-b:4,5-b']difurans are efficiently
      prepared by an iodine-promoted double cyclization. This new heterocyclic core is
      readily modified by the attachment of alkyl chains for improved solubility. The
      use of these compounds for the synthesis of new conjugated polymers is also
      reported.

PMID- 22850651
TI  - Our time to lead.
AB  - Case management has evolved from a grassroots method to assist patients and
      facilities to navigate changes in the healthcare system, to a fully fledged
      profession with core competencies, Standards of Practice, and an evidence-based
      peer review journal. With the latest healthcare reform, it is clear that case
      management leads to many initiatives: it is our time to lead.

PMID- 22850652
TI  - Government of Canada announces funding to support case managers in the health
      care sector.

PMID- 22850653
TI  - Improving pediatric patient outcomes: comparing two case management models.
AB  - PURPOSE OF THE STUDY: Case management (CM) is a growing and evolving profession.
      Outcomes-based research that identifies the role of CM is needed in health care
      today. Case management has been recognized as a way to help patients experience
      high-quality and cost-effective care. The purpose of this nonexperimental,
      retrospective research study was to examine two CM models and their effect on
      patient outcomes, including length of hospital stay and readmission to the
      hospital within 30 days of discharge with the same diagnosis. PRIMARY PRACTICE
      SETTING: The study was completed at two acute care pediatric hospitals in
      separate geographical regions of the country. METHODOLOGY AND SAMPLE: Two CM
      models were compared by conducting a retrospective patient chart review. Seven
      hundred pediatric patient charts were reviewed to determine whether the patient
      outcomes met patient outcomes of interest. All patients were diagnosed with
      asthma and were between the ages of 2 and 18 years. RESULTS: Analysis of data
      indicated that the length of hospital stay at Hospital A was significantly
      shorter than the length of hospital stay for patients admitted to Hospital B.
      However, hospital readmission rates within 30 days of discharge at Hospital A
      versus Hospital B indicated no significant difference. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: Further research that examines different CM models must
      account for variables such as complexity of disease process, age of patient on
      admission to the hospital, and relevance of discharge teaching.

PMID- 22850655
TI  - Case management programs for hospital readmission prevention.
AB  - PURPOSE/OBJECTIVES: This article examines the recent hospital emphasis on
      preventing hospital readmission. This article also identifies hospital programs
      that help prevent such readmissions by using a systematic approach to transitions
      of care. PRIMARY PRACTICE SETTING(S): Hospital case management departments.
      FINDINGS/CONCLUSIONS: A coordinated, patient-focused transition of care plan is a
      key element in preventing hospital readmissions. IMPLICATIONS FOR CASE MANAGEMENT
      PRACTICE: Leaders in hospital case management will have new demands placed on
      them to prevent patients from returning to the hospital after discharge. Leaders
      may choose to model demonstration programs, or they may implement unique
      strategies that support readmission prevention efforts.

PMID- 22850657
TI  - Effect of minimally invasive technique on return to work and narcotic use
      following transforaminal lumbar inter-body fusion: a review.
AB  - PURPOSE OF STUDY: Low back pain is one of the most prevalent and disabling
      musculoskeletal conditions affecting the working population in the United States.
      Informed, shared decision making among patients, clinicians, and case managers
      about treatment options for chronic low back pain-including the role of spinal
      fusion where medically necessary-can have a meaningful impact on return to work,
      normal function, and economic outcomes. Minimally invasive techniques for lumbar
      spinal fusion, including transforaminal lumbar interbody fusion (MIS TLIF) have
      recently been introduced with the goal of smaller operative wounds, less tissue
      trauma, and faster postoperative recovery when compared with open fusion.
      Although similar long-term clinical outcomes have been reported for MIS TLIF and
      open TLIF, the relative merits with respect to workplace productivity have not
      been comprehensively investigated. Time to return to work and narcotic
      independence after MIS TLIF and open TLIF are important parameters that may
      affect overall workplace productivity, and as such are the focus of this study.
      PRIMARY PRACTICE SETTING(S): This study was performed via a review of the
      literature. METHODOLOGY AND SAMPLE: We performed a systematic literature review
      to identify all published articles that reported on the postoperative outcomes of
      patients, as assessed by return to work or narcotic independence status or both,
      following MIS TLIF or open TLIF. A cumulative comparison was made for all
      included MIS TLIF versus open TLIF surgeries. RESULTS: Seventy-four published
      studies reported postoperative outcomes following MIS TLIF or open TLIF; only
      five (6.8%) studies directly described time to return to work or duration of
      narcotic use postoperatively or both, and were therefore included into the
      analysis of this review. Four studies in the published literature describe time
      to return to work following MIS TLIF or open TLIF, and two studies describe time
      to narcotic independence. Overall, the reviewed literature suggests that MIS TLIF
      may be associated with an accelerated time to narcotic independence and return to
      work versus open TLIF. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: There are
      limited data regarding time to return to work and duration of postoperative
      narcotic use following TLIF for low back pain. The available data appear to
      suggest that MIS TLIF may be associated with accelerated return to work and
      narcotic independence compared with open TLIF. Further analysis will be necessary
      to quantify the impact of MIS TLIF on workplace productivity and the indirect
      costs borne by patients and employers. Such information will be of value to case
      managers, disability managers, employers, patients, and clinicians aligned on
      reducing morbidity and hastening return to normal function.

PMID- 22850658
TI  - Culturally competent case managers establish rapport, connections in pursuit of
      patient outcomes.

PMID- 22850659
TI  - Dying to get home.

PMID- 22850660
TI  - Legal & regulatory issues.

PMID- 22850661
TI  - Hey coach, can you help me get back to work?

PMID- 22850662
TI  - Accessibility and the medical home:  resources and issues for case managers.

PMID- 22850663
TI  - Chiral phosphine-catalyzed asymmetric allylic alkylation of 3-substituted
      benzofuran-2(3H)-ones or oxindoles with Morita-Baylis-Hillman carbonates.
AB  - An efficient chiral phosphine-catalyzed asymmetric substitution reaction of MBH
      carbonates with 3-substituted benzofuran-2(3H)-ones or 3-substituted oxindoles
      has been described in this context, giving the corresponding allylic alkylation
      products bearing adjacent quaternary and tertiary stereogenic centers in high
      yields, moderate diastereoselectivities and high enantioselectivities under mild
      conditions.

PMID- 22850664
TI  - Youth Quality of Life Instrument-Research version (YQOL-R): psychometric
      properties in a community sample.
AB  - OBJECTIVE: To test some psychometric properties of the Brazilian-Portuguese
      version of the Youth Quality of Life Instrument-Research (YQOL-R) in a community
      sample of Brazilian adolescents. METHODS: This is a cross-sectional community
      study conducted in six schools of the catchment area of a family health unit.
      From an original population of 2,754 students from 10 to 17 years old, we
      randomly selected 419 to answer the Brazilian-Portuguese version of the YQOL-R.
      We tested reliability, known group differences (using anxiety symptoms and
      bullying involvement), and factor structure. RESULTS: The YQOL-R showed a good
      internal consistency and had an adequate and expected known group differences
      with both bullying and anxiety. The factor structure of the conceptual model was
      partially supported by our analysis. CONCLUSIONS: The Brazilian-Portuguese
      version of the YQOL-R showed sufficiently good psychometric properties. Further
      studies are needed in order to better investigate alternative configurations of
      the factor structure.

PMID- 22850665
TI  - Local Artemis dysfunction may be one molecular mechanism for androgenetic
      alopecia via telomere shortening.

PMID- 22850666
TI  - Critical sequences of phenomena in the progression of atherosclerotic lesions,
      with reference to the role of microvessels.
AB  - Atherosclerosis affects the inner layers of human arteries, and causes major
      problems by blocking, directly or indirectly, the flow of blood. This paper
      concerns the growth of atherosclerotic lesions (atherogenesis), in particular
      potential factors that may allow a form of 'positive feedback' that drives the
      development of lesions, and considers the role of microvessels. The lesions of
      atherosclerosis have previously been compared to, or thought of as, sites of
      inflammation, and involve the accumulation of cells, including large lipid
      containing macrophages, and extracellular elements. In tissues other than
      arteries inflammation may involve, amongst other phenomena, a resolution stage
      with the removal or departure of macrophages via lymphatics. However, the inner
      aspects of large arteries do not normally demonstrate lymphatics or other
      microvessels, and there is evidence from animal work that the lack of vessels
      effectively contributes to the development of atherosclerosis, as this limits the
      egress of macrophages and other elements. Conversely, in humans microvessels have
      been suggested to play a key role in the progress of atherosclerotic lesions. The
      importance of microvessels is herein considered, in particular the potentially
      paradoxical situation where as stated the lack of microvessels can be considered
      to allow atherosclerosis, but on the other hand these structures are involved in
      lesion development - the explanation can be seen to relate to the relatively
      short length of time which is assessable in animal models, compared to the
      lengthy period over which lesions appear to develop in humans. In addition,
      consideration is given to other factors, including haemodynamic factors related
      to the physical presence of lesions, which could lead to phenomena that can be
      regarded as a vicious cycle of events that lead to growth of the lesion.
      Specifically initial inflammation may lead to scarring and anatomical distortion,
      which through haemodynamic and physical factors leads to more damage, more
      inflammation and scarring, and so on.

PMID- 22850668
TI  - Ciguatoxins activate specific cold pain pathways to elicit burning pain from
      cooling.
AB  - Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most
      common form of ichthyosarcotoxism, which presents with peripheral sensory
      disturbances, including the pathognomonic symptom of cold allodynia which is
      characterized by intense stabbing and burning pain in response to mild cooling.
      We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by
      targeting specific unmyelinated and myelinated primary sensory neurons. These
      include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and
      tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously
      expressed TRPA1, but when co-expressed with Na(v) channels, sodium channel
      activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that
      is responsible for the development of cold allodynia, as evidenced by a large
      reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres
      and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional
      MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD
      (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1
      deficient mice, confirming an important role for TRPA1 in the pathogenesis of
      cold allodynia.

PMID- 22850669
TI  - Arabidopsis Argonaute MID domains use their nucleotide specificity loop to sort
      small RNAs.
AB  - The 5'-nucleotide of small RNAs associates directly with the MID domain of
      Argonaute (AGO) proteins. In humans, the identity of the 5'-base is sensed by the
      MID domain nucleotide specificity loop and regulates the integrity of miRNAs. In
      Arabidopsis thaliana, the 5'-nucleotide also controls sorting of small RNAs into
      the appropriate member of the AGO family; however, the structural basis for this
      mechanism is unknown. Here, we present crystal structures of the MID domain from
      three Arabidopsis AGOs, AtAGO1, AtAGO2 and AtAGO5, and characterize their
      interactions with nucleoside monophosphates (NMPs). In AtAGOs, the nucleotide
      specificity loop also senses the identity of the 5'-nucleotide but uses more
      diverse modes of recognition owing to the greater complexity of small RNAs found
      in plants. Binding analyses of these interactions reveal a strong correlation
      between their affinities and evolutionary conservation.

PMID- 22850670
TI  - Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans.
AB  - In recent years, the Piwi pathway has been shown to regulate the silencing of
      mobile genetic elements. However, we know little about how Piwi pathways impose
      silencing and even less about trans-generational stability of Piwi-induced
      silencing. We demonstrate that the Caenorhabditis elegans Piwi protein PRG-1 can
      initiate an extremely stable form of gene silencing on a transgenic, single-copy
      target. This type of silencing is faithfully maintained over tens of generations
      in the absence of a functional Piwi pathway. Interestingly, RNAi can also trigger
      permanent gene silencing of a single-copy transgene and the phenomenon will be
      collectively referred to as RNA-induced epigenetic silencing (RNAe). RNAe can act
      in trans and is dependent on endogenous RNAi factors. The involvement of factors
      known to act in nuclear RNAi and the fact that RNAe is accompanied by repressive
      chromatin marks indicate that RNAe includes a transcriptional silencing
      component. Our results demonstrate that, at least in C. elegans, the Piwi pathway
      can impose a state of gene silencing that borders on 'permanently silent'. Such a
      property may be more widely conserved among Piwi pathways in different animals.

PMID- 22850671
TI  - Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation
      and chemotaxis.
AB  - The CXC chemokine receptor 2 (CXCR2) on neutrophils, which recognizes chemokines
      produced at the site of infection, plays an important role in antimicrobial host
      defenses such as neutrophil activation and chemotaxis. Staphylococcus aureus is a
      successful human pathogen secreting a number of proteolytic enzymes, but their
      influence on the host immune system is not well understood. Here, we identify the
      cysteine protease Staphopain A as a chemokine receptor blocker. Neutrophils
      treated with Staphopain A are unresponsive to activation by all unique CXCR2
      chemokines due to cleavage of the N-terminal domain, which can be neutralized by
      specific protease inhibitors. Moreover, Staphopain A inhibits neutrophil
      migration towards CXCR2 chemokines. By comparing a methicillin-resistant S.
      aureus (MRSA) strain with an isogenic Staphopain A mutant, we demonstrate that
      Staphopain A is the only secreted protease with activity towards CXCR2. Although
      the inability to cleave murine CXCR2 limits in-vivo studies, our data indicate
      that Staphopain A is an important immunomodulatory protein that blocks neutrophil
      recruitment by specific cleavage of the N-terminal domain of human CXCR2.

PMID- 22850672
TI  - Regulation of mammalian transcription by Gdown1 through a novel steric crosstalk
      revealed by cryo-EM.
AB  - In mammals, a distinct RNA polymerase II form, RNAPII(G) contains a novel subunit
      Gdown1 (encoded by POLR2M), which represses gene activation, only to be reversed
      by the multisubunit Mediator co-activator. Here, we employed single-particle cryo
      electron microscopy (cryo-EM) to disclose the architectures of RNAPII(G), RNAPII
      and RNAPII in complex with the transcription initiation factor TFIIF, all to ~19
      A. Difference analysis mapped Gdown1 mostly to the RNAPII Rpb5 shelf-Rpb1 jaw,
      supported by antibody labelling experiments. These structural features correlate
      with the moderate increase in the efficiency of RNA chain elongation by RNAP
      II(G). In addition, our updated RNAPII-TFIIF map showed that TFIIF tethers
      multiple regions surrounding the DNA-binding cleft, in agreement with cross
      linking and biochemical mapping. Gdown1's binding sites overlap extensively with
      those of TFIIF, with Gdown1 sterically excluding TFIIF from RNAPII, herein
      demonstrated by competition assays using size exclusion chromatography. In
      summary, our work establishes a structural basis for Gdown1 impeding initiation
      at promoters, by obstruction of TFIIF, accounting for an additional dependent
      role of Mediator in activated transcription.

PMID- 22850673
TI  - Mouse Rif1 is a key regulator of the replication-timing programme in mammalian
      cells.
AB  - The eukaryotic genome is replicated according to a specific spatio-temporal
      programme. However, little is known about both its molecular control and
      biological significance. Here, we identify mouse Rif1 as a key player in the
      regulation of DNA replication timing. We show that Rif1 deficiency in primary
      cells results in an unprecedented global alteration of the temporal order of
      replication. This effect takes place already in the first S-phase after Rif1
      deletion and is neither accompanied by alterations in the transcriptional
      landscape nor by major changes in the biochemical identity of constitutive
      heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S
      transition and chromatin re-organization after DNA replication. Together, these
      data offer a novel insight into the global regulation and biological significance
      of the replication-timing programme in mammalian cells.

PMID- 22850674
TI  - Rif1 regulates the replication timing domains on the human genome.
AB  - DNA replication is spatially and temporally regulated during S-phase. DNA
      replication timing is established in early-G1-phase at a point referred to as
      timing decision point. However, how the genome-wide replication timing domains
      are established is unknown. Here, we show that Rif1 (Rap1-interacting-factor-1),
      originally identified as a telomere-binding factor in yeast, is a critical
      determinant of the replication timing programme in human cells. Depletion of Rif1
      results in specific loss of mid-S replication foci profiles, stimulation of
      initiation events in early-S-phase and changes in long-range replication timing
      domain structures. Analyses of replication timing show replication of sequences
      normally replicating early is delayed, whereas that normally replicating late is
      advanced, suggesting that replication timing regulation is abrogated in the
      absence of Rif1. Rif1 tightly binds to nuclear-insoluble structures at late-M-to
      early-G1 and regulates chromatin-loop sizes. Furthermore, Rif1 colocalizes
      specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S
      replication domains that are restrained from being activated at early-S-phase.
      Our results indicate that Rif1 plays crucial roles in determining the replication
      timing domain structures in human cells through regulating higher-order chromatin
      architecture.

PMID- 22850676
TI  - Orthostatic tolerance testing in a prospective cohort of adolescents with chronic
      fatigue syndrome and recovered controls following infectious mononucleosis.
AB  - Chronic fatigue syndrome (CFS) is a complex condition responsible for marked
      functional impairment. The authors recently reported that 6 months following
      acute infectious mononucleosis (IM), 13%, of adolescents met criteria for CFS.
      The authors' objective was to assess standing orthostatic tolerance (SOT) in
      adolescents with CFS and in controls 6 months following IM. In all, 36 of 39
      adolescents diagnosed with CFS 6 months following IM and 43 of 50 recovered
      controls had SOT testing (SOTT) performed. chi(2) Analysis was performed to study
      the relationships between SOTT and the diagnosis of CFS. Adolescents diagnosed
      with CFS and recovered controls did not differ significantly in age, weight, or
      body mass index. The authors found that 9 of 36 adolescents with CFS (25%) versus
      9 of 43 recovered controls (21%) had an abnormal SOTT, which was not a
      statistically significant difference. Adolescents who meet criteria for CFS 6
      months following IM do not have, as a group, more standing orthostatic
      intolerance than recovered controls.

PMID- 22850675
TI  - A stomatin dimer modulates the activity of acid-sensing ion channels.
AB  - Stomatin proteins oligomerize at membranes and have been implicated in ion
      channel regulation and membrane trafficking. To obtain mechanistic insights into
      their function, we determined three crystal structures of the conserved stomatin
      domain of mouse stomatin that assembles into a banana-shaped dimer. We show that
      dimerization is crucial for the repression of acid-sensing ion channel 3 (ASIC3)
      activity. A hydrophobic pocket at the inside of the concave surface is open in
      the presence of an internal peptide ligand and closes in the absence of this
      ligand, and we demonstrate a function of this pocket in the inhibition of ASIC3
      activity. In one crystal form, stomatin assembles via two conserved surfaces into
      a cylindrical oligomer, and these oligomerization surfaces are also essential for
      the inhibition of ASIC3-mediated currents. The assembly mode of stomatin
      uncovered in this study might serve as a model to understand oligomerization
      processes of related membrane-remodelling proteins, such as flotillin and
      prohibitin.

PMID- 22850677
TI  - Management of radicular pain in rheumatic disease: insight for the physician.
AB  - Rheumatologists are still relatively unaware of the causes, presentation,
      diagnosis and management of radicular pain. This is against a background of
      increasing evidence of the presence and importance of radicular problems in
      patients with rheumatological disorders. When they coexist in patients,
      differentiating between nociceptive and neuropathic pain is clinically important
      because these components require different pain management strategies.
      Consequently, it is essential that rheumatologists become skilled in identifying
      as well as managing both forms of pain. This review will serve to further
      increase awareness among rheumatologists of this important issue as well as
      discuss the practical aspects of managing these conditions. The evaluation of
      patients requires very careful history taking and full thorough neurological
      examination. Diagnostic testing is suggested mainly to confirm the diagnosis and
      aetiology in patients with persistent symptoms despite conservative treatment.
      Neuroimaging is recommended for patients with acute radicular pain with
      progressive neurological deficits or those with high suspicion of neoplasm or
      epidural abscess. If neuroimaging does not confirm diagnosis, electrophysiology
      studies may be helpful. The management of this condition is multifaceted and
      involves physicians and allied healthcare professionals as well as the patients
      who should be encouraged to participate in self-management programmes.
      Nociceptive and neuropathic pain often coexists in patients with rheumatic
      disease. There are challenges to making the diagnosis of radicular pain in these
      patients. The diagnosis is primarily clinical but pathophysiological issues,
      diversity in symptoms, the multiple mechanisms of action and difficulties in
      communication between patients and their doctors as well as variable response to
      therapy pose challenges to the effective management of these patients. Despite
      these difficulties and challenges, it is essential that rheumatologists
      familiarize themselves with the management of radicular pain in rheumatic
      diseases. The evaluation of patients requires very careful history taking, aided
      by the use of an appropriate screening tool and full, thorough neurological
      examination. In addition, investigations such as the use of imaging or
      electrophysiology studies when required may help to differentiate between the
      pain phenotypes.

PMID- 22850678
TI  - Terminal differentiation of cardiac and skeletal myocytes induces permissivity to
      AAV transduction by relieving inhibition imposed by DNA damage response proteins.
AB  - Gene therapy vectors based on the adeno-associated virus (AAV) are extremely
      efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and
      retina. The reason for their exquisite tropism for these cells has long remained
      elusive. Here, we show that upon terminal differentiation, cardiac and skeletal
      myocytes downregulate proteins of the DNA damage response (DDR) and that this
      markedly induces permissivity to AAV transduction. We observed that expression of
      members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV
      genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon
      myoblast differentiation in vitro; in both cases, withdrawal of the cells from
      the cell cycle coincided with increased AAV permissivity. Treatment of
      proliferating cells with short-interfering RNAs (siRNAs) against the MRN
      proteins, or with microRNA-24, which is normally upregulated upon terminal
      differentiation and negatively controls the Nbs1 levels, significantly increased
      permissivity to AAV transduction. Consistently, delivery of these small RNAs to
      the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte
      transduction. Collectively, these findings support the conclusion that cellular
      DDR proteins inhibit AAV transduction and that terminal cell differentiation
      relieves this restriction.

PMID- 22850679
TI  - Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene
      therapy improves survival of dogs with spontaneous bone cancer.
AB  - Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however,
      its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL
      gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to
      standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had
      greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation)
      compared to pretreatment biopsies or to tumors from dogs that did not receive Ad
      FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte
      infiltration scores >1 (in a 3-point scale), as well as in dogs that had
      apoptosis scores in the top 50th percentile (determined by cleaved caspase-3).
      Survival was no different than that expected from standard of care alone in dogs
      with inflammation scores <=1 or apoptosis scores in the bottom 50th percentile.
      Reduced Fas expression by tumor cells was associated with prognostically
      advantageous inflammation, and this was seen only in dogs that received Ad-FasL.
      Together, the data suggest that Ad-FasL gene therapy improves survival in a
      subset of large animals with naturally occurring tumors, and that at least in
      some tumor types like osteosarcoma, it is most effective when tumor cells fail to
      express Fas.

PMID- 22850680
TI  - Oral administration of recombinant adeno-associated virus-mediated bone
      morphogenetic protein-7 suppresses CCl(4)-induced hepatic fibrosis in mice.
AB  - Fibrogenesis and hepatocyte degeneration are the main pathological processes in
      chronic liver diseases. Transforming growth factor-beta1 (TGF-beta1) is the key
      profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is
      a potent antagonist of TGF-beta1 and an antifibrotic factor. In this study, we
      generated a recombinant adeno-associated virus carrying BMP-7 (AAV-BMP-7) and
      tested its ability to suppress carbon tetrachloride (CCl(4))-induced hepatic
      fibrosis when orally administered to mice. Our results show that the ectopic
      expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV-BMP-7
      administration led to the long-term elevation of serum BMP-7 concentrations and
      resulted in the drastic amelioration of CCl(4)-induced hepatic fibrosis in BALB/c
      mice. Immunostaining for alpha-smooth muscle actin (alpha-SMA) and desmin
      demonstrated that AAV-BMP-7 inhibited the activation of hepatic stellate cells
      (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7
      promoted hepatocyte proliferation, as confirmed by an increase in the amount of
      proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that
      received AAV-BMP-7. Our results clearly indicate that BMP-7 is capable of
      inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest
      that oral AAV-BMP-7 could be developed into a safe, simple, and effective therapy
      for hepatic fibrosis.

PMID- 22850681
TI  - Extended normal life after AAVrh10-mediated gene therapy in the mouse model of
      Krabbe disease.
AB  - Globoid cell leukodystrophy (GLD) or Krabbe disease is a neurodegenerative
      disorder caused by the deficiency of the lysosomal enzyme galactocerebrosidase
      (GALC). This deficiency results in accumulation of certain galactolipids
      including psychosine which is cytotoxic for myelin-producing cells. Treatment of
      human patients at this time is limited to hematopoietic stem cell transplantation
      (HSCT) that appears to slow the progression of the disease when performed in
      presymptomatic patients. In this study, adeno-associated virus (AAV) serotype
      rh10-(AAVrh10) expressing mouse GALC was used in treating twitcher (twi) mice,
      the mouse model of GLD. The combination of intracerebroventricular,
      intracerebellar, and intravenous (iv) injection of viral particles in neonate twi
      mice resulted in high GALC activity in brain and cerebellum and moderate to high
      GALC activity in spinal cord, sciatic nerve, and some peripheral organs.
      Successfully treated mice maintained their weight with no or very little
      twitching, living up to 8 months. The physical activities of the long-lived
      treated mice were comparable to wild type for most of their lives. Treated mice
      showed normal abilities to mate, to deliver pups, to nurse and to care for the
      newborns. This strategy alone or in combination with other therapeutic options
      may be applicable to treatment of human patients.

PMID- 22850684
TI  - Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat
      model by insulin administration.
AB  - Type 1 diabetes subjects are characterized by impaired direct pathway synthesis
      of hepatic glycogen that is unresponsive to insulin therapy. Since it is not
      known whether this is an irreversible defect of insulin-dependent diabetes,
      direct and indirect pathway glycogen fluxes were quantified in streptozotocin
      (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous
      or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied
      at 18 days post-STZ treatment. One group was administered I-SC and another I-IP
      as two daily injections of short-acting insulin at the start of each light and
      dark period for days 9-18. A third group did not receive any insulin, and a
      fourth group of nondiabetic rats was used as control. Glycogen synthesis via
      direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were
      determined over the nocturnal feeding period using deuterated water. Direct
      pathway was residual in STZ rats, and glucokinase activity was also reduced
      significantly from control levels. Insulin administration restored both net
      glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic
      control levels and improved the lipogenic pathway despite an inefficient
      normalization of the gluconeogenic pathway. We conclude that the reduced direct
      pathway flux is not an irreversible defect of insulin-dependent diabetes.

PMID- 22850683
TI  - Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during
      short-term fasting and nutrient excess.
AB  - We have suggested previously that Tribbles homolog 3 (TRIB3), a negative
      regulator of Akt activity in insulin-sensitive tissues, could mediate glucose
      induced insulin resistance in muscle under conditions of chronic hyperglycemia
      (Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin
      M, Garvey WT. Am J Physiol Endocrinol Metab 298: E565-E576, 2010). In the current
      study, we have assessed short-term physiological regulation of TRIB3 in skeletal
      muscle and adipose tissues by nutrient excess and fasting as well as TRIB3's
      ability to modulate glucose transport and mitochondrial oxidation. In Sprague
      Dawley rats, we found that short-term fasting enhanced insulin sensitivity
      concomitantly with decrements in TRIB3 mRNA (66%, P < 0.05) and protein (81%, P <
      0.05) in muscle and increments in TRIB3 mRNA (96%, P < 0.05) and protein (~10
      fold, P < 0.05) in adipose tissue compared with nonfasted controls. On the other
      hand, rats fed a Western diet for 7 days became insulin resistant concomitantly
      with increments in TRIB3 mRNA (155%, P < 0.05) and protein (69%, P = 0.0567) in
      muscle and a decrease in the mRNA (76%, P < 0.05) and protein (70%, P < 0.05) in
      adipose. In glucose transport and mitochondria oxidation studies using skeletal
      muscle cells, we found that stable TRIB3 overexpression impaired insulin
      stimulated glucose uptake without affecting basal glucose transport and increased
      both basal glucose oxidation and the maximal uncoupled oxygen consumption rate.
      With stable knockdown of TRIB3, basal and insulin-stimulated glucose transport
      rates were increased, whereas basal glucose oxidation and the maximal uncoupled
      oxygen consumption rate were decreased. In conclusion, TRIB3 impacts glucose
      uptake and oxidation oppositely in muscle and fat according to levels of nutrient
      availability. The above data for the first time implicate TRIB3 as a potent
      physiological regulator of insulin sensitivity and mitochondrial glucose
      oxidation under conditions of nutrient deprivation and excess.

PMID- 22850685
TI  - A switch in Sertoli cell responsiveness to FSH may be responsible for robust
      onset of germ cell differentiation during prepubartal testicular maturation in
      rats.
AB  - FSH and Testosterone (T) regulate spermatogenesis via testicular Sertoli cells
      (Sc), which bear receptors for these hormones. Despite sufficient circulating
      levels of FSH and T postnatally, predominant appearance of spermatogonia B and
      spermatocytes is not discernible until 11 and 18 days of postnatal age,
      respectively, in rat testes. In an attempt to explore the underlying causes, we
      cultured Sc from neonatal (5- and 9-day-old) and prepubertal (12- and 19-day-old)
      rat testes and compared the status of FSH receptor (FSH-R) and androgen receptor
      (AR) signaling. Protein and mRNA levels of FSH-R and AR remained uniform in
      cultured Sc from all age groups. Androgen binding ability of AR was similar, and
      T-induced nuclear localization of AR was discernible in Sc from all age groups.
      Binding of FSH to FSH-R, subsequent production of cAMP, and mRNA of stem cell
      factor (SCF) and glial cell line-derived neurotrophic factor (GDNF), known to be
      essential for the robust differentiation of repopulating spermatogonia, were
      significantly augmented in prepubertal Sc compared with those in neonatal Sc.
      However, treatment of neonatal Sc with cholera toxin or forskolin, which
      stimulate cAMP production bypassing FSH-R, demonstrated a concomitant rise in SCF
      and GDNF mRNA expression, which was similar to the FSH-mediated rise observed in
      prepubertal Sc. These observations suggested that, during prepubertal Sc
      maturation, the ability of FSH-R to respond to FSH is significantly augmented and
      is associated with the robust differentiation of repopulating spermatogonia, and
      such a switch in Sc from FSH-resistant to FSH-responsive mode during prepubertal
      development may underlie the initiation of robust spermatogenesis.

PMID- 22850686
TI  - Mechanisms of action of islet neogenesis-associated protein: comparison of the
      full-length recombinant protein and a bioactive peptide.
AB  - Islet neogenesis-associated protein (INGAP) was discovered in the partially duct
      obstructed hamster pancreas as a factor inducing formation of new duct-associated
      islets. A bioactive portion of INGAP, INGAP(104-118) peptide (INGAP-P), has been
      shown to have neogenic and insulin-potentiating activity in numerous studies,
      including recent phase 2 clinical trials that demonstrated improved glucose
      homeostasis in both type 1 and type 2 diabetic patients. Aiming to improve INGAP
      P efficacy and to understand its mechanism of action, we cloned the full-length
      protein (rINGAP) and compared the signaling events induced by the protein and the
      peptide in RIN-m5F cells that respond to INGAP with an increase in proliferation.
      Here, we show that, although both rINGAP and INGAP-P signal via the Ras/Raf/ERK
      pathway, rINGAP is at least 100 times more efficient on a molar basis than INGAP
      P. For either ligand, ERK1/2 activation appears to be pertussis toxin sensitive,
      suggesting involvement of a G protein-coupled receptor(s). However, there are
      clear differences between the peptide and the protein in interactions with the
      cell surface and in the downstream signaling. We demonstrate that fluorescent
      labeled rINGAP is characterized by clustering on the membrane and by slow
      internalization (<=5 h), whereas INGAP-P does not cluster and is internalized
      within minutes. Signaling by rINGAP appears to involve Src, in contrast to INGAP
      P, which appears to activate Akt in addition to the Ras/Raf/ERK1/2 pathway. Thus
      our data suggest that interactions of INGAP with the cell surface are important
      to consider for further development of INGAP as a pharmacotherapy for diabetes.

PMID- 22850687
TI  - An essential role of p27 downregulation in fenvalerate-induced cell growth in
      human uterine leiomyoma and smooth muscle cells.
AB  - Previously, we reported that fenvalerate (Fen) promotes proliferation of human
      uterine leiomyoma (UtLM) cells by enhancing progression of cells from G(0)-G(1)
      to S phase through molecular mechanisms independent of estrogen receptor-alpha
      and -beta. The cyclin-dependent kinase (CDK) inhibitor p27, which blocks G(1) to
      S phase transitions and is an important regulator of CDK2, is often decreased in
      hormonally regulated diseases, including uterine leiomyomas. Therefore, we were
      interested in whether Fen could regulate the expression of p27 and whether p27
      might play a role in Fen-induced cell proliferation. Expression of p27 in Fen
      treated UtLM and uterine smooth muscle cells (UtSMCs) was examined. We found that
      p27 mRNA was significantly downregulated and that protein levels were decreased
      in both cell types treated with 10 MUM Fen for 24 h compared with respective
      controls. Overexpression of p27 in UtLM cells and UtSMCs using an adenovirus
      doxycycline (Dox)-regulated Tet-off system abrogated the proliferative effects of
      Fen, as evidenced by decreased total cell numbers and BrdU incorporation. Fen
      treatment increased CDK2 mRNA expression levels; however, overexpression of p27
      also abolished this effect. In contrast, Dox treatment dramatically restored the
      above muted responses. Finally, we utilized siRNA to knock down p27 expression.
      After transfection, mRNA levels of p27 were downregulated in UtLM cells and
      UtSMCs and total cell numbers and BrdU incorporation increased significantly
      compared with nontransfected cells. Fen treatment in the presence of p27
      silencing enhanced the increased cell counts and BrdU labeling in UtLM cells and
      UtSMCs. Taken together, these results indicate that p27 downregulation is
      critical for Fen-induced cell proliferation.

PMID- 22850688
TI  - [Slow release versus immediate release oxcarbazepine in difficult-to-treat focal
      epilepsy: a multicenter, randomized, open, controlled, parallel group phase III
      study].
AB  - BACKGROUND: The aim of the study was an assessment of the tolerability and
      efficacy of slow release oxcarbazepine (OXC-MR) versus immediate release OXC (OXC
      IR) after forced titration in patients with focal epileptic seizures with and
      without secondary generalization who had previously not become seizure-free under
      OXC-IR with or without concomitant antiepileptic drugs. The primary study
      variable was to assess the maximum tolerated dosage with OXC-MR and OXC-IR.
      PATIENTS AND METHODS: This was designed as a multicenter, randomized, open,
      controlled, parallel group phase III study. After randomization patients received
      OXC-MR or OXC-IR for a study period of 26 days. The initial dosage of 900 mg,
      1,200 mg or 1,500 mg OXC was increased every 5 days by 300 mg up to a maximum
      daily dosage of 2,700 mg. In cases of intolerable adverse events dosage could be
      reduced by 150 mg 2 days after an increase. Adverse events and executive
      abilities were assessed with the questionnaire "Adverse Event Profile plus" and
      with the Epitrack(r) test protocol. Serum concentrations of OXC and its active
      metabolite were measured in a part of the patient group. RESULTS: The 71 patients
      (54% male, age: 19-70 years) enrolled in the study were randomized. The maximum
      mean daily OXC dosage at the end of the study period was 1,950 mg with OXC-MR and
      thus statistically significantly higher than in OXC-IR group (1,650 mg, p =
      0.022). The number of causally related adverse events was lower in the OXC-MR
      group (n = 104 versus n = 138 with OXC-IR) and CNS-related adverse events such as
      dizziness, tremor, somnolence and headache occurred significantly less often with
      OXC-MR (OXC-MR 65.7%, OXC-IR 88.9%, p = 0.01). Fluctuations of serum
      concentrations of the active metabolite were less pronounced under the OXC-MR
      regimen. CONCLUSIONS: Due to better tolerability OXC-MR allowed higher
      maintenance dosages to be reached than OXC-IR. In spite of a higher mean daily
      dosage adverse events and especially CNS-related adverse events occurred less
      often than with OXC-IR.

PMID- 22850689
TI  - Impaired colony-forming capacity of circulating endothelial progenitor cells in
      patients with emphysema.
AB  - Chronic obstructive pulmonary disease (COPD) is classified into emphysema and
      chronic bronchitis, which are thought to result from different pathophysiological
      pathways.  Smoking-induced lung parenchymal destruction and inadequate repair are
      involved in the pathogenesis of emphysema.  In addition, decreased expression of
      vascular endothelial growth factor and increased endothelial cell apoptosis in
      the lung may participate in emphysema pathogenesis.  As stem cells, circulating
      endothelial progenitor cells (EPCs) may play a key role in the maintenance of
      vascular integrity by replacing and repairing the damaged endothelial cells in
      the tissues.  To determine whether the lack of appropriate repair by circulating
      EPCs in cases of smoking-induced endothelial cell injury participates in
      emphysema pathogenesis, we determined the association between the colony-forming
      or migratory capacity of circulating EPCs and the presence of emphysema in 51
      patients with COPD.  The patients were divided into emphysema (n = 23) and non
      emphysema groups (n = 28) based on high-resolution computed tomography.  Twenty
      two smokers with normal lung function and 14 normal non-smokers served as
      controls.  Circulating EPCs isolated from patients with emphysema showed
      significantly lower colony-forming units (CFUs) than those from patients with non
      emphysema group, smokers with normal lung function, and normal non-smokers.  EPCs
      from patients with emphysema showed significantly lower migratory capacity than
      those from normal non-smoking controls (p < 0.05).  On multivariate analysis, the
      EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903
      0.987, p = 0.011).  Thus, impaired functions of circulating EPCs may contribute
      to the development of emphysema.

PMID- 22850690
TI  - Detection of blaKPC-2 in a carbapenem-resistant Kluyvera georgiana.

PMID- 22850691
TI  - High-resolution melting analysis for rapid characterization of qnr alleles in
      clinical isolates and detection of two novel alleles, qnrB25 and qnrB42.
AB  - OBJECTIVES: qnr genes are plasmid-mediated quinolone resistance genes. Five qnr
      families have been described with several alleles (7 alleles of qnrA, 53 alleles
      of qnrB, 1 allele of qnrC, 1 allele of qnrD and 6 alleles of qnrS). Their
      detection requires a PCR specific for each qnr family and further sequencing for
      allele characterization. METHODS: High-resolution melt curve analysis (HRMA) was
      coupled to multiplex and simplex real-time PCR assays for detection and
      characterization of qnrA, qnrB and qnrS alleles. The protocol was set using 27
      reference strains harbouring the most frequent alleles and was applied to 55
      clinical isolates unknown for qnr positivity. RESULTS: Out of the 27 reference
      strains tested, 21 alleles showed distinct profiles using HRMA: 6 qnrA, 12 qnrB
      and 3 qnrS. For the qnrB alleles showing similar profiles, we gathered them into
      four groups that were easily distinguished. For the alleles that we could not
      test, in silico analysis showed that they would be identified using the HRMA
      protocol set. Among the clinical isolates, 28 qnr-positive isolates were detected
      and the qnr allele was characterized as 8 qnrA1, 4 qnrB1, 5 qnrB2, 3 qnrB4, 1
      qnrB8, 1 qnrB5, 3 qnrS1 and 1 qnrS2, with concordant results with PCR sequencing.
      Two new qnrB alleles were detected and distinguished using HMRA. They were
      further designated as qnrB25 and qnrB42. CONCLUSIONS: We developed an HRMA assay
      for characterizing the qnr alleles in clinical isolates. This high-throughput
      method can be used to screen a large number of isolates. This method allowed the
      detection of new qnrB alleles.

PMID- 22850692
TI  - Indications and outcomes of antifungal therapy in French patients with
      haematological conditions or recipients of haematopoietic stem cell
      transplantation.
AB  - OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients
      with haematological conditions. We describe diagnoses, therapeutic management and
      outcomes in unselected consecutive patients from haematological facilities
      treated for suspected or documented IFD. METHODS: In this observational
      prospective study, children/adults with haematological conditions or
      haematopoietic stem cell transplantation (HSCT) were recruited upon start of non
      prophylactic systemic antifungal treatment in 37 French haematological facilities
      (December 2007 to December 2008). IFD episodes were classified according to the
      2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults
      and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68%
      neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59%
      probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven
      other IFD) and 20% classified as possible IFD. The remaining cases were assigned
      to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were
      classified as possible/probable/proven IFD by day 7. Treatment was thus initiated
      early in 59% of patients; liposomal amphotericin B and caspofungin were the most
      common single-agent therapies. The 12 week mortality was 18% for probable/proven
      aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9%
      for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes
      (log rank P = 0.016); it was dependent on age, complete remission of underlying
      haematological disease and mechanical ventilation. CONCLUSIONS: In this
      comprehensive sample of haematological patients receiving antifungal treatment,
      we observe a widespread resort to early therapy and a low mortality rate,
      including in patients with probable or proven IFD.

PMID- 22850693
TI  - Diversity of naturally occurring Ambler class B metallo-beta-lactamases in
      Erythrobacter spp.
AB  - OBJECTIVES: In silico analysis identified a metallo-beta-lactamase (MBL) in
      Erythrobacter litoralis HTCC2594, sharing 55% amino acid identity with NDM-1. The
      aim of this work was to characterize the chromosomally encoded MBLs from several
      Erythrobacter spp. that may represent potential reservoirs of acquired MBLs.
      METHODS: Erythrobacter citreus, Erythrobacter flavus, Erythrobacter longus,
      Erythrobacter aquimaris and Erythrobacter vulgaris were from the Pasteur
      Institute collection, France. DNA was extracted and used for shotgun cloning, and
      beta-lactamases were expressed in Escherichia coli. MICs for resulting E. coli
      recombinant strains were determined by Etest. The deduced amino acid sequences
      were analysed and compared with BLASTP. Enzymatic activity of bacterial extracts
      from recombinant E. coli strains was determined by UV spectrophotometry with
      imipenem (100 MUM) as substrate. RESULTS: Resulting E. coli recombinant strains
      harboured hypothetical MBL-encoding genes. MICs of beta-lactams showed decreased
      susceptibility to carbapenems only for E. coli (pFLA-1) and E. coli (pLON-1),
      expressing the MBL from E. flavus and E. longus, respectively. MBLs from
      different Erythrobacter spp. shared weak amino acid identity, ranging from 45%
      to75% identity. They differed greatly from that of E. litoralis HTCC2594 (and NDM
      1), sharing only 11%-23% identity. Enzymatic activity against imipenem was
      detectable but weak in all these recombinant E. coli strains, except E. coli
      (pFLA-1), in which specific activity was significantly higher. CONCLUSIONS:
      Several chromosomally located MBLs have been identified from Erythrobacter spp.
      They share weak amino acid identity and are very weakly related to other acquired
      MBLs (10%-23%).

PMID- 22850695
TI  - Multifunctionalized luminescent lanthanide complexes from nonadentate
      phosphonylated bis-pyrazolyl-pyridine ligands.
AB  - A series of lanthanide complexes has been prepared from ligands constructed from
      a bis-pyrazolyl-pyridine core bearing various chelating arms with anionic mixed
      carboxylate/phosphonate or phosphonate substituents. These ligands form
      particularly stable complexes with Eu(III) and Tb(III) which display outstanding
      spectroscopic properties, with excited state lifetimes ranging from 2.6 to 3.2 ms
      and quantum yields in the 16 to 48% range in water or phosphate buffer. The
      complexes are significantly more stable than those of analogous ligands bearing
      only carboxylate groups. Some of the new ligands have a central and flexible
      pendent link suitable for bio-labelling.

PMID- 22850694
TI  - Concomitant antibiotic and mercury resistance among gastrointestinal microflora
      of feral brook trout, Salvelinus fontinalis.
AB  - Twenty-nine bacterial isolates representing eight genera from the
      gastrointestinal tracts of feral brook trout Salvelinus fontinalis (Mitchell)
      demonstrated multiple maximal antibiotic resistances and concomitant broad
      spectrum mercury (Hg) resistance. Equivalent viable plate counts on tryptic soy
      agar supplemented with either 0 or 25 MUM HgCl(2) verified the ubiquity of
      mercury resistance in this microbial environment. Mercury levels in lake water
      samples measured 1.5 ng L(-1); mercury concentrations in fish filets ranged from
      81.8 to 1,080 ng g(-1) and correlated with fish length. The presence of similar
      antibiotic and Hg resistance patterns in multiple genera of gastrointestinal
      microflora supports a growing body of research that multiple selective genes can
      be transferred horizontally in the presence of an unrelated individual selective
      pressure. We present data that bioaccumulation of non-point source Hg pollution
      could be a selective pressure to accumulate both antibiotic and Hg resistant
      bacteria.

PMID- 22850696
TI  - Graphene electrochemistry: fundamental concepts through to prominent
      applications.
AB  - The use of graphene, a one atom thick individual planar carbon layer, has
      exploded in a plethora of scientific disciplines since it was reported to possess
      a range of unique and exclusive properties. Despite graphene being explored
      theoretically since the 1940s and known to exist since the 1960s, the recent
      burst of interest from a large proportion of scientists globally can be
      correlated with work by Geim and Novoselov in 2004/5, who reported the so-called
      "scotch tape method" for the production of graphene in addition to identifying
      its unique electronic properties which has escalated into graphene being reported
      to be superior in a superfluity of areas. Consequently, many are involved in the
      pursuit of producing new methodologies to fabricate pristine graphene on an
      industrial scale in order to meet the current world-wide appetite for graphene.
      One area which receives considerable interest is the field of electrochemistry,
      where graphene has been reported to be beneficial in various applications ranging
      from sensing through to energy storage and generation and carbon based molecular
      electronics. Electrochemistry is an interfacial technique which is dominated by
      processes that occur at the solid-liquid interface and thus with the correct
      understanding can be beneficially utilised to characterise the surface under
      investigation. In this tutorial review we overview fundamental concepts of
      Graphene Electrochemistry, making electrochemical characterisation accessible to
      those who are working on new methodologies to fabricate graphene, bridging the
      gap between materials scientists and electrochemists and also assisting those
      exploring graphene in electrochemical areas, or that wish to start to. An
      overview of the recent understanding of graphene modified electrodes is also
      provided, highlighting prominent applications reported in the current literature.

PMID- 22850697
TI  - Using a reference population yardstick to calibrate and compare genetic diversity
      reported in different studies: an example from the brown bear.
AB  - In species with large geographic ranges, genetic diversity of different
      populations may be well studied, but differences in loci and sample sizes can
      make the results of different studies difficult to compare. Yet, such comparisons
      are important for assessing the status of populations of conservation concern. We
      propose a simple approach of using a single well-studied reference population as
      a 'yardstick' to calibrate results of different studies to the same scale,
      enabling comparisons. We use a well-studied large carnivore, the brown bear
      (Ursus arctos), as a case study to demonstrate the approach. As a reference
      population, we genotyped 513 brown bears from Slovenia using 20 polymorphic
      microsatellite loci. We used this data set to calibrate and compare
      heterozygosity and allelic richness for 30 brown bear populations from 10
      different studies across the global distribution of the species. The simplicity
      of the reference population approach makes it useful for other species, enabling
      comparisons of genetic diversity estimates between previously incompatible
      studies and improving our understanding of how genetic diversity is distributed
      throughout a species range.

PMID- 22850698
TI  - Thyroid hormone responsive QTL and the evolution of paedomorphic salamanders.
AB  - The transformation of ancestral phenotypes into novel traits is poorly understood
      for many examples of evolutionary novelty. Ancestrally, salamanders have a
      biphasic life cycle with an aquatic larval stage, a brief and pronounced
      metamorphosis, followed by a terrestrial adult stage. Repeatedly during
      evolution, metamorphic timing has been delayed to exploit growth-permissive
      environments, resulting in paedomorphic salamanders that retain larval traits as
      adults. We used thyroid hormone (TH) to rescue metamorphic phenotypes in
      paedomorphic salamanders and then identified quantitative trait loci (QTL) for
      life history traits that are associated with amphibian life cycle evolution:
      metamorphic timing and adult body size. We demonstrate that paedomorphic tiger
      salamanders (Ambystoma tigrinum complex) carry alleles at three moderate effect
      QTL (met1-3) that vary in responsiveness to TH and additively affect metamorphic
      timing. Salamanders that delay metamorphosis attain significantly larger body
      sizes as adults and met2 explains a significant portion of this variation. Thus,
      substitution of alleles at TH-responsive loci suggests an adaptive pleiotropic
      basis for two key life-history traits in amphibians: body size and metamorphic
      timing. Our study demonstrates a likely pathway for the evolution of novel
      paedomorphic species from metamorphic ancestors via selection of TH-response
      alleles that delay metamorphic timing and increase adult body size.

PMID- 22850699
TI  - Spontaneous hybrids between native and exotic Rubus in the Western United States
      produce offspring both by apomixis and by sexual recombination.
AB  - Facultative asexual reproduction is a trait commonly found in invasive species.
      With a combination of sexual and asexual reproductive modes, such species may
      adapt to new environments via sexual recombination during range expansion, while
      at the same time having the benefits of asexuality such as the maintenance of
      fitness effects that depend upon heterozygosity. In the Western United States,
      native species of Rubus (Rosaceae) reproduce sexually whereas exotic naturalized
      Rubus species reproduce by pseudogamous apomixis. We hypothesized that new
      asexual lineages of Rubus could arise from hybridization in this range. To detect
      hybridization between native and exotic Rubus, we genotyped 579 individuals
      collected across California, Oregon and Washington with eight nuclear
      microsatellites and two chloroplast markers. Principal Coordinate Analysis and
      Bayesian clustering revealed a limited amount of hybridization of the native R.
      ursinus with the exotic R. armeniacus and R. pensilvanicus, as well as cultivated
      varieties. Genetic distances between these hybrids and their offspring indicated
      that both R. ursinus * R. armeniacus and R. ursinus * R. pensilvanicus produced a
      mix of apomictic and sexual seeds, with sexual seeds being more viable. Although
      neither of these hybrid types is currently considered invasive, they model the
      early stages of evolution of new invasive lineages, given the potential for fixed
      heterosis and the generation of novel genotypes. The hybrids also retain the
      ability to increase their fitness via sexual recombination and natural selection.
      Mixed reproductive systems such as those described here may be an important step
      in the evolution of asexual invasive species.

PMID- 22850700
TI  - Reversible 3-Li storage reactions of amorphous phosphorus as high capacity and
      cycling-stable anodes for Li-ion batteries.
AB  - An amorphous phosphorus/carbon nanocomposite demonstrates a reversible 3-Li
      storage capacity of 2355 mAh g(-1) with an excellent capacity retention of 90%
      over 100 cycles and a superior power capability with 62% of its capacity
      realizable at a very high rate of 8000 mA g(-1), possibly serving as a high
      capacity and high rate alternative anode for next-generation Li-ion batteries.

PMID- 22850701
TI  - Influence of arterial hypertension on colonic healing in rats.
AB  - PURPOSE: Evaluation of colonic healing in spontaneously hypertensive rats.
      METHODS: Fifty male, young and inbred rats were used. Twenty-five Wistar Kyoto
      rats (WKY) as control and twenty-five spontaneously hypertensive rats (SHR) as an
      experimental group. Colotomy and bowel suture at 2.5 cm from the peritoneal
      reflection were performed. All animals were allocated randomly into sub-groups
      for review at the third, seventh and fourteenth days after surgery. We evaluated
      the concentration of angiotensin II, the burst pressure, epithelialization, the
      organization of the tunics of the bowel wall, inflammatory response and collagen
      deposition. RESULTS: The burst pressure, epithelialization, organization of the
      tunics and collagen deposition was not significant between groups. The
      inflammatory reaction was more intense in the control group on the third
      postoperative day (p=0.023) as the experimental group on the remaining time.
      CONCLUSION: Systemic arterial hypertension in rats did not influence
      significantly the healing process of colonic anastomoses.

PMID- 22850702
TI  - Role of wild type p53 and double suicide genes in interventional therapy of liver
      cancer in rabbits.
AB  - PURPOSE: To investigate the feasibility of interventional lipiodol embolism and
      multigene therapy in combination with focal chemotherapy in the treatment of VX2
      liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm
      in diameter were randomly divided into five groups (n=9 per group). In Group 1,
      animals were treated with 0.9% sodium chloride. In Group 2, animals received
      lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene
      therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy.
      In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy.
      Ultrasonography and CT were performed before and at ten days after interventional
      therapy. RESULTS: The VX2 model of liver cancer was successfully established in
      rabbits and interventional therapy smoothly performed. At ten days after
      interventional therapy, significant difference in the tumor volume was noted
      among five groups (p<0.05) and different treatments could inhibit the cancer
      growth. The inhibition of cancer growth was the most evident in the Group 5.
      Factorial analysis revealed gene therapy with p53 or TK/CD and lipiodol embolism
      independently exert significantly inhibitory effect on cancer growth. In
      addition, the suppression on tumor growth rate was the most obvious in the Group
      5. CONCLUSIONS: Combination of gene therapy with lipiodol embolism can
      effectively inhibit the cancer growth and prolong the survival time. These
      findings demonstrate the effectiveness of multigene therapy in combination with
      lipiodol embolism in the treatment of liver cancer.

PMID- 22850703
TI  - Angiogenesis inhibition by green propolis and the angiogenic effect of L-lysine
      on bladder cancer in rats.
AB  - PURPOSE: To determine the effects of water-soluble derivative of green propolis
      in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl)
      nitrosamine (BBN). METHODS: Nine groups were established, where six of them
      (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14
      weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated
      respectively with water, L-lysine (300 mg/kg/day), celecoxib (30 mg/kg/day) and
      propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from
      the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by
      histological sections stained for the marker CD-31 and analyzed with specific
      software. RESULTS: The microvascular density in bladder carcinomas was lower
      (p<0.01) in rats receiving propolis than in controls given carcinogen only. On
      the other hand, the microvascular density of tumors in rats receiving carcinogen
      and L-lysine for 40 weeks from the beginning of carcinogen treatment was
      significantly higher (p<0.01) than in the corresponding controls. CONCLUSION:
      Water-soluble derivative of propolis inhibits angiogenesis in BBN-induced rat
      bladder cancer, while L-lysine treatment stimulates angiogenesis if initiated
      concurrently with BBN.

PMID- 22850704
TI  - Impact of flaxseed intake upon metabolic syndrome indicators in female Wistar
      rats.
AB  - PURPOSE: To evaluate whether the prolonged consumption of flaxseed minimize the
      factors that trigger MS in healthy rats. METHODS: Pregnant rats were divided
      immediately after delivery into two groups during the lactation period, a control
      group (CG) receiving casein-based diet with 17% of protein, and a Flaxseed group
      (FG) with casein-based diet plus 25% of flaxseed. At weaning, 12 offspring of
      each group continued to receive the same feed but with 10% of protein up to 200
      days old. RESULTS: FG showed a significant reduction in body weight (p=0.001),
      total cholesterol levels (p<0.0001), triglycerides (p=0.0001), and glucose
      (p=0.001). CONCLUSION: The flaxseed alters the indicators related to development
      of metabolic syndrome, because it has beneficial effects on lipids and glucose
      profiles and prevents the excess of body weight gain.

PMID- 22850705
TI  - Evaluation of oxidative stress in mice subjected to aerobic exercise.
AB  - PURPOSE: To evaluate the influence of aerobic exercise on oxidative stress in
      mice. METHODS: The study included twenty female mice Mus musculus-Swiss divided
      into two groups: sedentary control (GA) and exercise (GB), each containing ten
      animals. All animals underwent an adaptation period of seven days isolated in
      individual boxes. After this period, the animals in the exercise group (GB) were
      trained in angled running wheel with circumference of 25 cm assembled on an
      articulated axle during five minutes for three consecutive days. On the fourth
      day, they underwent an exercise program of one session lasting 45 minutes. The
      evaluation of oxidative stress was performed by determining the levels of
      malondialhyde derived of lipid peroxidation by the TBA method. The samples were
      read in a spectrophotometer at 535 nm. RESULTS: No significant difference was
      observed in the intergroup comparison of MDA levels in the tissues evaluated. A
      significant difference was observed in the intragroup comparison of MDA levels in
      the control group (p = 0.0201).The Tukeys' post hoc test indicated significantly
      lower values of MDA in the smooth muscle in relation to plasma. In the analysis
      of variance in the exercise group, a significant difference between tissues (p =
      0.0009), with significantly lower values in the smooth muscle in relation to
      plasma (p<0.001) and higher in striated muscle in relation to smooth muscle
      (p<0.05) was observed. CONCLUSION: There was no change in the analysis of
      oxidative stress in mice which were undergone a single session of aerobic
      exercise.

PMID- 22850706
TI  - Association of acepromazine with propofol in giant Amazon turtles Podocnemis
      expansa reared in captivity.
AB  - PURPOSE: To evaluate the effects of different concentrations of an anesthetic
      association in giant amazon turtles (Podocnemis expansa). METHODS: Twenty healthy
      P. expansa of both sexes weighing between 1.0 and 1.5kg commercially bred in the
      Araguaia River Valley, Goias, Brazil, were separated into two groups (G1 n=10 and
      G2 n=10). Each group received a respective protocol: P1= acepromazine (0.5 mg/kg
      IM) and propofol (5 mg/kg IV) and P2 = acepromazine (0.5 mg/kg IM) and propofol
      (10 mg/kg IV). The acepromazine was administered in the left thoracic member and
      the propofol in the cervical vertebral sinus. Assessments were made of the
      anesthetic parameters of locomotion, muscle relaxation, response to pain stimuli
      in the right thoracic and pelvic members and heartbeat. RESULTS: The anesthetic
      induction time was the same for both protocols (P1 and P2); however the P2
      effects were of a longer duration. CONCLUSION: The sedation achieved with both
      protocols (P1 and P2) were satisfactory for the biological sample collection,
      physical examinations and minor surgeries on this species.

PMID- 22850707
TI  - Surgical application of fascia lata as a pericardial substitute in rabbits.
AB  - PURPOSE: To use fascia lata instead of pericardium and observe the presence of
      adhesions. METHODS: Twenty rabbits were divided into two group of ten. In group
      A, a 1*1 cm segment of pericardium was excised and resutured. In group B excised
      pericardium was substituted for autologous fascia lata. RESULTS: In the
      comparison of microscopic adhesion rate between two groups A, B after eight
      weeks, there was no significant statistical difference. CONCLUSION: Fascia lata
      is safe and it can be substituted for pericardium especially in repeat sternotomy
      in repairing congenital heart defects to avoid heart injury.

PMID- 22850708
TI  - Effect of N-acetylcysteine on pulmonary cell death in a controlled hemorrhagic
      shock model in rats.
AB  - PURPOSE: To evaluate the effect of N-acetylcysteine (NAC) combined with fluid
      resuscitation on pulmonary cell death in rats induced with controlled hemorrhagic
      shock (HS). METHODS: Two arteries (MAP calculation and exsanguination) and one
      vein (treatments) were catheterized in 22 anesthetized rats. Two groups of male
      albino rats were induced with controlled HS at 35mmHg MAP for 60 min. After this
      period, the RL group was resuscitated with Ringer's lactate and the RL+NAC group
      was resuscitated with Ringer's lactate combined with 150mg/Kg NAC. The control
      group animals were cannulated only. The animals were euthanized after 120 min of
      fluid resuscitation. Lung tissue samples were collected to evaluate the
      following: histopathology, TUNEL and imunohistochemical expression of caspase 3.
      RESULTS: RL showed a greater number of cells stained by TUNEL than RL + NAC, but
      there was no change in caspase 3 expression in any group. CONCLUSION: N
      acetylcysteine associate to fluid resuscitation, after hemorrhagic shock,
      decreased cell death attenuating lung injury.

PMID- 22850709
TI  - Anatomical and functional evaluation of tympanoplasty using a transitory natural
      latex biomembrane implant from the rubber tree Hevea brasiliensis.
AB  - PURPOSE: To compare the role of transitory latex and sylastic(r) implants in
      tympanoplasty on the closure of tympanic perforations. METHODS: A randomized
      double-blind prospective study was conducted on 107 patients with chronic otitis
      media submitted to underlay tympanoplasty and divided at random into three
      groups: control with no transitory implant, latex membrane group, and sylastic(r)
      membrane group. RESULTS: Greater graft vascularization occurred in the latex
      membrane group (p<0.05). Good biocompatibility was obtained with the use of the
      latex and silicone implants, with no effect on the occurrence of infection,
      otorrhea or otorragy. CONCLUSION: The use of a transitory latex implant induced
      greater graft vascularization, with a biocompatible interaction with the tissue
      of the human tympanic membrane.

PMID- 22850710
TI  - Comparison of two methods of femoral tunnel preparation in single-bundle anterior
      cruciate ligament reconstruction: a prospective randomized study.
AB  - PURPOSE: To prospectively compare therapeutic effect of femoral tunnel
      preparation through the tibial tunnel and the anteromedial (AM) portal in single
      bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Between June
      2008 and October 2010, 76 patients underwent single-bundle ACL reconstruction by
      autogenous grafting of semitendinosus and gracilis tendon. All cases were
      randomly divided into two groups according to the method of femoral tunnel
      preparation: transtibial (TT) group (n=38) and anteromedial (AM) group (n=38).
      Lysholm knee score and the KT-1000 anterior laxity at 30 degrees  of pre-and post
      operation were assessed for two groups. RESULTS: Sixty-five patients (TT group,
      34; AM group, 31) were followed up for more than 12 months, with a follow-up rate
      of 86%. The Lysholm knee score and the KT-1000 anterior laxity 12 months after
      operation were significantly better than before reconstruction. The Lysholm knee
      score and the KT-1000 anterior laxity were not significantly different between
      the TT and AM groups after operation. CONCLUSION: Femoral tunnel preparation
      through tibial tunnel or the anteromedial portal in single-bundle anterior
      cruciate ligament reconstruction shows same therapeutic effects.

PMID- 22850711
TI  - Biliopancreatic diversion with duodenojejunal exclusion associated with truncal
      vagotomy: a new proposal for type 2 diabetes mellitus treatment.
AB  - PURPOSE: To evaluate the effectiveness of the biliopancreatic diversion surgery
      with duodenojejunal exclusion in combination with truncal vagotomy in type 2
      diabetes mellitus (T2DM) patients with overweight or class I or II obesity.
      METHODS: The study included ten patients with T2DM and class I or II obesity or
      overweight who were subjected to biliopancreatic diversion with duodenojejunal
      exclusion in combination with truncal vagotomy. The blood glucose levels during
      the pre- and postoperative periods were compared using the Friedman test. The
      significance level adopted was 5%. RESULTS: There were significant differences
      between preoperative and postoperative blood glucose levels at three months
      (p=0.01), six months (p=0.001) and 12 months (p=0.001). There was also a
      significant difference between one month postoperative blood glucose and six
      months postoperative blood glucose (p=0.01). Glycosylated hemoglobin levels
      decreased in 80% of patients, there was marked improvement in their lipid
      profiles, and the average BMI reduction was 7.0+/-1.5 kg/m2 at 12 months after
      the surgery. CONCLUSION: In patients with type 2 diabetes mellitus associated
      with class I/II obesity or overweight, performing biliopancreatic diversion with
      duodenojejunal exclusion in combination with truncal vagotomy resulted in
      glycemic control, reduction of excess weight, and improvement of lipid profile 12
      months after the surgery.

PMID- 22850712
TI  - Cryopreserved tracheal segments: a new tool for bench surgical training in
      thoracic surgery.
AB  - PURPOSE: To present a new low-cost high fidelity bench model of cryopreserved
      trachea that can be used to learn surgical skills from medical students to
      cardiothoracic surgery fellows. METHODS: Ten tracheas were harvested from ten non
      trachea related research dogs at the moment of euthanasia. Each trachea was
      trimmed in six or seven rings segments. They were cryopreserved and stored during
      60 days. The day programmed for surgical skills practice, they were thawed to
      room temperature. RESULTS: Forty segments have been used. After defrosting, all
      the segments kept their normal anatomic shape and structural integrity. Two
      incisions were made on every tracheal segment and sutured with running or
      separate stitches with 5-0 polypropilene. There were no complications such as
      cartilage ruptures, neither tears on the mucosae, the cartilages nor the
      membranous posterior membrane. CONCLUSIONS: The cryopreserved trachea is a high
      fidelity, practical, reproducible, portable, low-cost bench model. It allows
      cardiothoracic fellows to learn how to handle a trachea, as well as to perfect
      their surgical and suture abilities before applying them on a real patient's
      trachea.

PMID- 22850713
TI  - Review of experimental models for inducing hepatic cirrhosis by bile duct
      ligation and carbon tetrachloride injection.
AB  - PURPOSE: To present a review about a comparative study of bile duct ligation
      versus carbon tetrachloride Injection for inducing experimental liver cirrhosis.
      METHODS: This research was made through Medline/PubMed and SciELO web sites
      looking for papers on the content "induction of liver cirrhosis in rats". We have
      found 107 articles but only 30 were selected from 2004 to 2011. RESULTS: The most
      common methods used for inducing liver cirrhosis in the rat were administration
      of carbon tetrachloride (CCl4) and bile duct ligation (BDL). CCl4 has induced
      cirrhosis from 36 hours to 18 weeks after injection and BDL from seven days to
      four weeks after surgery. CONCLUSION: For a safer inducing cirrhosis method BDL
      is better than CCl4 because of the absence of toxicity for researches and shorter
      time for achieving it.

PMID- 22850714
TI  - Hypokalemic paralysis in a girl with dental and renal calculi. Distal renal
      tubular acidosis (RTA).

PMID- 22850716
TI  - Assessing journal influence: impacted wisdom.

PMID- 22850719
TI  - Chemoprotection in brain tumor patients: another success for stem cell gene
      therapy.

PMID- 22850720
TI  - T-cell therapy for viral infections following transplantation: why stop at three
      viruses?

PMID- 22850722
TI  - O4-alkyl-2'-deoxythymidine cross-linked DNA to probe recognition and repair by O6
      alkylguanine DNA alkyltransferases.
AB  - DNA duplexes containing a directly opposed O(4)-2'-deoxythymidine-alkyl-O(4)-2'
      deoxythymidine (O(4)-dT-alkyl-O(4)-dT) interstrand cross-link (ICL) have been
      prepared by the synthesis of cross-linked nucleoside dimers which were converted
      to phosphoramidites to produce site specific ICL. ICL duplexes containing alkyl
      chains of four and seven methylene groups were prepared and characterized by mass
      spectrometry and nuclease digests. Thermal denaturation experiments revealed four
      and seven methylene containing ICL increased the T(m) of the duplex with respect
      to the non-cross-linked control with an observed decrease in enthalpy based on
      thermodynamic analysis of the denaturation curves. Circular dichroism experiments
      on the ICL duplexes indicated minimal difference from B-form DNA structure. These
      ICL were used for DNA repair studies with O(6)-alkylguanine DNA alkyltransferase
      (AGT) proteins from human (hAGT) and E. coli (Ada-C and OGT), whose purpose is to
      remove O(6)-alkylguanine and in some cases O(4)-alkylthymine lesions. It has been
      previously shown that hAGT can repair O(6)-2'-deoxyguanosine-alkyl-O(6)-2'
      deoxyguanosine ICL. The O(4)-dT-alkyl-O(4)-dT ICL prepared in this study were
      found to evade repair by hAGT, OGT and Ada-C. Electromobility shift assay (EMSA)
      results indicated that the absence of any repair by hAGT was not a result of
      binding. OGT was the only AGT to show activity in the repair of oligonucleotides
      containing the mono-adducts O(4)-butyl-4-ol-2'-deoxythymidine and O(4)-heptyl-7
      ol-2'-deoxythymidine. Binding experiments conducted with hAGT demonstrated that
      the protein bound O(4)-alkylthymine lesions with similar affinities to O(6)
      methylguanine, which hAGT repairs efficiently, suggesting the lack of O(4)
      alkylthymine repair by hAGT is not a function of recognition.

PMID- 22850721
TI  - Harnessing a physiologic mechanism for siRNA delivery with mimetic lipoprotein
      particles.
AB  - Therapeutics based on RNA interference (RNAi) have emerged as a potential new
      class of drugs for treating human disease by silencing the target messenger RNA
      (mRNA), thereby reducing levels of the corresponding pathogenic protein. The
      major challenge for RNAi therapeutics is the development of safe delivery
      vehicles for small interfering RNAs (siRNAs). We previously showed that
      cholesterol-conjugated siRNAs (chol-siRNA) associate with plasma lipoprotein
      particles and distribute primarily to the liver after systemic administration to
      mice. We further demonstrated enhancement of silencing by administration of chol
      siRNA pre-associated with isolated high-density lipoprotein (HDL) or low-density
      lipoprotein (LDL). In this study, we investigated mimetic lipoprotein particle
      prepared from recombinant apolipoprotein A1 (apoA) and apolipoprotein E3 (apoE)
      as a delivery vehicle for chol-siRNAs. We show that apoE-containing particle (E
      lip) is highly effective in functional delivery of chol-siRNA to mouse liver. E
      lip delivery was found to be considerably more potent than apoA-containing
      particle (A-lip). Furthermore, E-lip-mediated delivery was not significantly
      affected by high endogenous levels of plasma LDL. These results demonstrate that
      E-lip has substantial potential as delivery vehicles for lipophilic conjugates of
      siRNAs.

PMID- 22850723
TI  - The discovery of CP violation in B-meson decays.
AB  - We present the KEK B-factory project, which discovered CP violation in B-meson
      decays and proved that the Kobayashi-Maskawa theory correctly explains CP
      violation in meson decays.

PMID- 22850725
TI  - Synthesis of neoproteoglycans using the transglycosylation reaction as a reverse
      reaction of endo-glycosidases.
AB  - A method for the synthesis of carbohydrate chains (glycosaminoglycans) and their
      coupling to peptides was investigated using proteoglycans. Glycosidases generally
      catalyze a hydrolytic reaction, but can also mediate the reverse reaction, which
      in this case is a transglycosylation. In the transglycosylation reaction of
      bovine testicular hyaluronidase, which is an endoglycosidase, glycosaminoglycans
      (hyaluronan and chondroitin sulfates) release disaccharide (uronic acid-N
      acetylhexosamine) moieties from non-reducing terminal sites, and then the
      liberated disaccharides are transferred immediately to the non-reducing termini
      of other glycosaminoglycan chains. Using such continuous reactions, it is
      possible to synthesize glycosaminoglycan chains according to a specific design.
      It then becomes possible to transfer glycosaminoglycan chains synthesized on a
      peptide to other peptides using the transglycosylation reaction of endo-beta
      xylosidase acting on the linkage region between a peptide and glycosaminoglycan
      chains of proteoglycans. We believe this approach will open a new field for the
      synthesis of homogeneous proteoglycans or their corresponding analogues.

PMID- 22850727
TI  - Stabilization of atmospheric carbon dioxide via zero emissions--an alternative
      way to a stable global environment. Part 1: examination of the traditional
      stabilization concept.
AB  - The concept of "stabilization" of atmospheric CO(2) concentration is re-examined
      in connection with climate-change mitigation strategies. A new "zero-emissions
      stabilization (Z-stabilization)" is proposed, where CO(2) emissions are reduced
      to zero at some time and thereafter the concentration is decreased by natural
      removal processes, eventually reaching an equilibrated stable state. Simplified
      climate experiments show that, under Z-stabilization, considerably larger
      emissions are permissible in the near future compared with traditional
      stabilization, with the same constraint on temperature rise. Over longer time
      scales, the concentration and temperature decrease close to their equilibrium
      values, much lower than those under traditional stabilization. The smaller
      temperature rise at final state is essential to avoid longer-term risk of sea
      level rise, a significant concern under traditional stabilization. Because of
      these advantages a Z-stabilization pathway can be a candidate of practical
      mitigation strategies as treated in Part 2.

PMID- 22850724
TI  - Guillain-Barre syndrome and anti-ganglioside antibodies: a clinician-scientist's
      journey.
AB  - Guillain-Barre syndrome (GBS) is the most frequent cause of acute flaccid
      paralysis. Having seen my first GBS patient in 1989, I have since then dedicated
      my time in research towards understanding the pathogenesis of GBS. Along with
      several colleagues, we identified IgG autoantibodies against ganglioside GM1 in
      two patients with GBS subsequent to Campylobacter jejuni enteritis. We proceeded
      to demonstrate molecular mimicry between GM1 and bacterial lipo-oligosaccharide
      of C. jejuni isolated from a patient with GBS. Our group then established a
      disease model for GBS by sensitization with GM1 or GM1-like lipo-oligosaccharide.
      With this, a new paradigm that carbohydrate mimicry can cause autoimmune
      disorders was demonstrated, making GBS the first proof of molecular mimicry in
      autoimmune disease. Patients with Fisher syndrome, characterized by
      ophthalmoplegia and ataxia, can develop the disease after an infection by C.
      jejuni. We showed that the genetic polymorphism of C. jejuni sialyltransferase,
      an enzyme essential to the biosynthesis of ganglioside-like lipo-oligosaccharides
      determines whether patients develop GBS or Fisher syndrome. This introduces
      another paradigm that microbial genetic polymorphism can determine the clinical
      phenotype of human autoimmune diseases. Similarities between the clinical
      presentation of Fisher syndrome and Bickerstaff brainstem encephalitis have
      caused debate as to whether they are in fact the same disease. We demonstrated
      that IgG anti-GQ1b antibodies were common to both, suggesting that they are part
      of the same disease spectrum. We followed this work by clarifying the nosological
      relationship between the various clinical presentations within the anti-GQ1b
      antibody syndrome. In this review, I wanted to share my journey from being a
      clinician to a clinician-scientist in the hopes of inspiring younger clinicians
      to follow a similar path.

PMID- 22850726
TI  - Unnatural base pair systems toward the expansion of the genetic alphabet in the
      central dogma.
AB  - Toward the expansion of the genetic alphabet of DNA, several artificial third
      base pairs (unnatural base pairs) have been created. Synthetic DNAs containing
      the unnatural base pairs can be amplified faithfully by PCR, along with the
      natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair
      systems now have high potential to open the door to next generation
      biotechnology. The creation of unnatural base pairs is a consequence of repeating
      "proof of concept" experiments. In the process, initially designed base pairs
      were modified to address their weak points. Some of them were artificially
      evolved to ones with higher efficiency and selectivity in polymerase reactions,
      while others were eliminated from the analysis. Here, we describe the process of
      unnatural base pair development, as well as the tests of their applications.

PMID- 22850728
TI  - Stabilization of atmospheric carbon dioxide via zero emissions--an alternative
      way to a stable global environment. Part 2: a practical zero-emissions scenario.
AB  - Following Part 1, a comparison of CO(2)-emissions pathways between "zero
      emissions stabilization (Z-stabilization)" and traditional stabilization is made
      under more realistic conditions that take into account the radiative forcings of
      other greenhouse gases and aerosols with the constraint that the temperature rise
      must not exceed 2  degrees C above the preindustrial level. It is shown that the
      findings in Part 1 on the merits of Z-stabilization hold under the more realistic
      conditions. The results clarify the scientific basis of the policy claim of 50%
      reduction of the world CO(2) emissions by 2050. Since the highest greenhouse gas
      (GHG) concentration and temperature occur only temporarily in Z-stabilization
      pathways, we may slightly relax the upper limit of the temperature rise. We can
      then search for a scenario with larger emissions in the 21st century; such a
      scenario may have potential for practical application. It is suggested that in
      this Z-stabilization pathway, larger emissions in the near future may be
      important from a socioeconomic viewpoint.

PMID- 22850731
TI  - A therapeutically viable photo-activated manganese-based CO-releasing molecule
      (photo-CO-RM).
AB  - A new class of photochemically-activated CO-releasing molecule (photo-CO-RM),
      based on a Mn(CO)(4)(C^N) system, is reported in this study. Three CO molecules
      are released per CO-RM molecule. Complex 3 is a fast releaser, thermally stable
      in the dark and a viable therapeutic agent.

PMID- 22850732
TI  - Recent advances on polyoxometalate-based molecular and composite materials.
AB  - Polyoxometalates (POMs) are a subset of metal oxides with unique physical and
      chemical properties, which can be reliably modified through various techniques
      and methods to develop sophisticated materials and devices. In parallel with the
      large number of new crystal structures reported in the literature, the
      application of these POMs towards multifunctional materials has attracted
      considerable attention. This critical review summarizes recent progress on POM
      based molecular and composite materials, and particularly highlights the emerging
      areas that are closely related to surface, electronic, energy, environment, life
      science, etc. (171 references).

PMID- 22850733
TI  - Investigation of cortical glutamate-glutamine and gamma-aminobutyric acid in
      obsessive-compulsive disorder by proton magnetic resonance spectroscopy.
AB  - Glutamatergic abnormalities in corticostriatal brain circuits are thought to
      underlie obsessive-compulsive disorder (OCD). Whether these abnormalities exist
      in adults with OCD is not clear. We used proton magnetic resonance spectroscopy
      (1H MRS) to test our hypothesis that unmedicated adults with OCD have reduced
      glutamate plus glutamine (Glx) levels in the medial prefrontal cortex (MPFC)
      compared with healthy controls. Levels of gamma-aminobutyric acid (GABA) were
      also explored. Twenty-four unmedicated adults with OCD and 22 matched healthy
      control subjects underwent 1H MRS scans at 3.0 T. Resonances of both Glx and GABA
      were obtained using the standard J-editing technique and assessed as ratios
      relative to voxel tissue water (W) in the MPFC (the region of interest) and the
      dorsolateral prefrontal cortex (DLPFC) to explore the regional specificity of any
      finding. In the MPFC, Glx/W did not differ by diagnostic group (p=0.98) or sex
      (p=0.57). However, GABA/W was decreased in OCD (2.16+/-0.46 * 10-3) compared with
      healthy controls (2.43+/-0.45 * 10-3, p=0.045); moreover, age of OCD onset was
      inversely correlated with MPFC GABA/W (r=-0.50, p=0.015). MPFC GABA/W was higher
      in females than in males. In the DLPFC, there were no main effects of diagnosis
      or gender on Glx/W or GABA/W. These data indicate that unmedicated adults with
      OCD do not have Glx abnormalities in a MPFC voxel that includes the pregenual
      anterior cingulate cortex. However, they may have decreased MPFC GABA levels. How
      GABA abnormalities might contribute to corticostriatal dysfunction in OCD
      deserves further study.

PMID- 22850734
TI  - Brain activation associated with attentional bias in smokers is modulated by a
      dopamine antagonist.
AB  - Attentional bias in substance-dependent individuals is the tendency to
      automatically direct the attention to substance-related cues in the environment.
      Attentional bias is known to be associated with clinical measures such as relapse
      or successful quitting in smokers. It has been suggested that attentional bias
      emerges as a consequence of dopaminergic activity evoked by substance-related
      cues. The current functional magnetic resonance imaging study employed a
      dopaminergic challenge in order to test whether brain activation associated with
      attentional bias in smokers could be modulated by a dopamine antagonist. A total
      of 25 smokers were compared with 24 controls. Participants were scanned twice
      while performing a pictorial attentional bias task. Haloperidol (2 mg), a
      selective D2/D3 dopamine antagonist, or placebo was orally administered 4 h
      before each scanning session in a double-blind randomized cross-over design.
      Imaging analyses were performed in a priori selected regions of interest. Results
      showed that smokers had enhanced brain activation compared with controls in the
      dorsal anterior cingulate cortex (dACC), right dorsolateral prefrontal cortex (r
      DLPFC), and left superior parietal lobe (I-SPL) after placebo. Group * medication
      interactions were found in the dACC and r-DLPFC, with no differences between
      groups in these regions after haloperidol. The current findings suggest that a
      pharmacologically induced reduction in dopamine normalizes brain activation
      associated with attentional bias in the dACC and DLPFC in smokers, probably
      because salience of these cues is no longer detected when dopamine activity is
      reduced.

PMID- 22850735
TI  - Impact of a microRNA MIR137 susceptibility variant on brain function in people at
      high genetic risk of schizophrenia or bipolar disorder.
AB  - A recent 'mega-analysis' combining genome-wide association study data from over
      40,000 individuals identified novel genetic loci associated with schizophrenia
      (SCZ) at genome-wide significance level. The strongest finding was a locus within
      an intron of a putative primary transcript for microRNA MIR137. In the current
      study, we examine the impact of variation at this locus (rs1625579, G/T; where T
      is the common and presumed risk allele) on brain activation during a sentence
      completion task that differentiates individuals with SCZ, bipolar disorder (BD),
      and their relatives from controls. We examined three groups of individuals
      performing a sentence completion paradigm: (i) individuals at high genetic risk
      of SCZ (n=44), (ii) individuals at high genetic risk of BD (n=90), and (iii)
      healthy controls (n=81) in order to test the hypothesis that genotype at
      rs1625579 would influence brain activation. Genotype groups were assigned as
      'RISK-' for GT and GG individuals, and 'RISK+' for TT homozygotes. The main
      effect of genotype was significantly greater activation in the RISK- individuals
      in the posterior right medial frontal gyrus, BA 6. There was also a significant
      genotype(*)group interaction in the left amygdala and left pre/postcentral gyrus.
      This was due to differences between the controls (where individuals with the RISK
      genotype showed greater activation than RISK+ subjects) and the SCZ high-risk
      group, where the opposite genotype effect was seen. These results suggest that
      the newly identified SCZ locus may influence brain activation in a manner that is
      partly dependent on the presence of existing genetic susceptibility for SCZ.

PMID- 22850736
TI  - White matter disruptions in adolescents exposed to childhood maltreatment and
      vulnerability to psychopathology.
AB  - Childhood maltreatment has been known to produce long-lasting impairments in
      behavioral, cognitive and social functioning, but their underlying mechanisms are
      not well-understood. A better understanding of their underlying mechanisms will
      aid in developing effective preventive interventions. Nineteen adolescent
      volunteers with no personal history of a psychiatric illness, but who were
      exposed to maltreatment during childhood, and 13 adolescent volunteers with no
      personal or family history of a psychiatric disorder (controls) underwent
      diffusion tensor imaging (DTI) studies. The participants were then followed
      longitudinally at 6-month intervals for up to 5 years to determine the onset of
      mood and substance use disorders. The associations among fractional anisotropy
      (FA) values obtained from the DTI scans at baseline and psychopathology at follow
      up were examined. At baseline, adolescents exposed to childhood maltreatment had
      significantly lower FA values in the left and right superior longitudinal
      fasciculi, right cingulum bundle projecting to the hippocampus, left inferior
      fronto-occipital fasciculus, and splenium of the corpus callosum compared with
      controls. Adolescents who developed major depressive disorder at follow-up had
      significantly lower FA values in the superior longitudinal fasciculi and the
      right cingulum-hippocampal projection compared with their counterparts who did
      not develop the illness. Adolescents who developed substance use disorder during
      follow-up had significantly lower FA values in the right cingulum-hippocampal
      projection than their counterparts without the disorder. These preliminary
      results suggest that white matter disruptions observed in adolescents exposed to
      childhood maltreatment may be associated with increased vulnerability to
      psychopathology, specifically depressive and substance use disorders.

PMID- 22850738
TI  - Comparisons of CYP2A6 genotype and enzyme activity between Swedes and Koreans.
AB  - The aim was to compare cytochrome P450 2A6 (CYP2A6) genotype and enzyme activity
      between Swedes and Koreans, and to investigate the influence of genotype, sex,
      age, cigarette smoking and oral contraceptive (OC) use on enzyme activity. The
      study involved 190 Swedes and 144 Koreans. Genotyping for CYP2A6*1B, *1*2, *4,
      *5, *7, *8, *9, *10, *18 and *19 alleles was done. Using caffeine as a probe, in
      vivo CYP2A6 activity was estimated by the 17U/17X urinary ratio. Multiple
      regression analysis indicated ethnicity (p=0.0001) and CYP2A6 genotype (p=0.006),
      but not sex, age, cigarette smoking or OC use as predictors of CYP2A6 activity.
      There were significant differences in CYP2A6 genotype distribution and enzyme
      activity between Swedes and Koreans. Functional CYP2A6 alleles and rapid
      genotypes were more frequent in Swedes, whereas the defective alleles and slow
      genotypes were more frequent in Koreans (p<=0.0001). Distribution of log 17U/17X
      was bimodal in Koreans but unimodal in Swedes with a common antimode at 0.01,
      classifying 3.16% of Swedes and 18.75% of Koreans as slow metabolizers. CYP2A6
      activity was higher in Swedes compared to Koreans (p<0.0001), even among carriers
      of rapid genotypes. We report major differences in CYP2A6 enzyme activity between
      Swedes and Koreans mainly due to CYP2A6 genetic variation but not exclusively.

PMID- 22850737
TI  - Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors
      in the balance of GABAergic and glutamatergic neurotransmission.
AB  - Biphasic effects of cannabinoids have been shown in processes such as feeding
      behavior, motor activity, motivational processes and anxiety responses. Using two
      different tests for the characterization of anxiety-related behavior (elevated
      plus-maze and holeboard), we first identified in wild-type C57BL/6N mice, two
      doses of the synthetic CB1 cannabinoid receptor agonist CP-55,940 with anxiolytic
      (1 MUg/kg) and anxiogenic properties (50 MUg/kg), respectively. To clarify the
      role of CB1 receptors in this biphasic effect, both doses were applied to two
      different conditional CB1 receptor knockout (KO) mouse lines, GABA-CB1-KO (CB1
      receptor inactivation in forebrain GABAergic neurons) and Glu-CB1-KO (CB1
      receptor inactivation in cortical glutamatergic neurons). We found that the
      anxiolytic-like effects of the low dose of cannabinoids are mediated via the CB1
      receptor on cortical glutamatergic terminals, because this anxiolytic-like
      response was abrogated only in Glu-CB1-KO mice. On the contrary, the CB1 receptor
      on the GABAergic terminals is required to induce an anxiogenic-like effect under
      a high-dose treatment because of the fact that this effect was abolished
      specifically in GABA-CB1-KO mice. These experiments were carried out in both
      sexes, and no differences occurred with the doses tested in the mutant mice.
      Interestingly, the positive allosteric modulation of GABA(B) receptor with GS
      39783 was found to largely abrogate the anxiogenic-like effect of the high dose
      of CP-55,940. Our results shed new light in further understanding the biphasic
      effects of cannabinoids at the molecular level and, importantly, pave the way for
      the development of novel anxiolytic cannabinoid drugs, which may have favorable
      effect profiles targeting the CB1 receptor on glutamatergic terminals.

PMID- 22850739
TI  - Genetic variations of NR1I3 and NR2B1 in Asian populations.
AB  - Several nuclear receptors are being increasingly recognized for their role as
      master xenosensors. Among them, CAR-RXRalpha heterodimer, as encoded by NR1I3 and
      NR2B1, responds to the presence of drug compounds and regulates the transcription
      of a wide array of genes involved in their disposition. To investigate the
      frequency distribution and linkage disequilibrium patterns of NR1I3 and NR2B1
      genetic variations, these genes were screened in 168 healthy local Asian
      subjects, namely Chinese, Malays, and Indians (n=56 subjects each). A total of 38
      and 88 SNPs were identified in NR1I3 and NR2B1, respectively. Among them, there
      were 13 and 43 novel SNPs present at low allelic frequencies (<10%) in NR1I3 and
      NR2B1, respectively. Notably, the genetic variations in the NR1I3 and NR2B1 genes
      were mainly confined to the introns whilst the exons were highly conserved across
      the ethnic populations. Indians harboured distinct frequency distributions from
      Chinese and Malays in both genes. Based on the linkage disequilibrium patterns of
      both genes, a number of tag-SNPs were selected for each population (n=8-13 for
      NR1I3; n=12-18 for NR2B1). In-silico prediction analyses revealed a number of
      possible functional SNPs. Our data would be valuable for future pharmacogenetic
      studies on the drug substrates of CAR-RXRalpha target genes.

PMID- 22850740
TI  - Clinical characteristics of children with lower respiratory tract infections are
      dependent on the carriage of specific pathogens in the nasopharynx.
AB  - A prospective clinical study was performed to correlate nasopharyngeal carriage
      of bacteria with the type of lower respiratory tract infections (LRTI) in
      hospitalised children. To determine bacterial load in nasopharyngeal aspirates
      (NPA) we used semiquantitative culturing and quantitative TaqMan-PCR for those
      pathogens difficult to culture. Specimens and clinical data were obtained from
      311 children between 0 and 16 years of age with LRTI during the period of 2006
      2008. The most common detected potentially pathogenic colonisers were Haemophilus
      influenzae (32.1 %), Moraxella catharralis (26.7 %), Staphylococcus aureus (17.7
      %) and Streptococcus pneumoniae (16.7 %). As expected S. aureus was the most
      common coloniser in children less than 4 months of age, whereas H. influenzae
      detection peaked in older children. Co-colonisation with other bacterial
      pathogens were more often observed in children with S. aureus (46 %) and S.
      pneumoniae (49 %) than in those with H. influenzae (30 %) or M. catharralis (27
      %). Children with S. aureus co-colonisation had higher levels of C-reactive
      protein, received antibiotics more frequently and stayed longer in hospital than
      those with S. aureus single colonisation. In contrast, children with H.
      influenzae, M. catharralis or S. pneumoniae colonisation suffered more often from
      pneumonia than children with S. aureus colonisation. Coloniser specific analysis
      of bacterial quantity revealed no significant reduction of the bacterial carriage
      from the first to the second NPA. No correlation of a high bacterial load and
      occurrence of pneumonia could be detected. In conclusion, clinical
      characteristics in children with LRTIs are associated with a specific bacterial
      set of colonisers detected in the nasopharynx rather than on their quantity.

PMID- 22850741
TI  - Clinical evaluation of new automated cytomegalovirus IgM and IgG assays for the
      Elecsys((r)) analyser platform.
AB  - Cytomegalovirus (CMV) is a leading cause of physical and neurological
      abnormalities in newborns. Hence, the diagnosis of CMV infection in pregnant
      women is necessary in order to allow appropriate management of their pregnancy.
      New assays have been developed for the Roche Elecsys(r) immunoassay platform that
      detect CMV-specific immunoglobulin (Ig)M and IgG, with the IgM assay designed to
      target IgM produced at the start of infection rather than IgM persisting later in
      infection. This study aimed to evaluate the performance of the new assays
      compared with other commercial kits widely distributed in laboratories. The
      performance of the Elecsys and comparator CMV IgM and IgG assays was assessed
      using 967 preselected patient samples characterised by CMV infection status, as
      well as being compared using 1,668 unselected clinical samples. The Elecsys CMV
      IgM and IgG assays performed consistently with comparator assays using the
      preselected samples. The Elecsys CMV IgM assay showed improved sensitivity
      compared with the Enzygnost(r) assay in primary infection (91.2 % vs. 79.4 %) and
      improved specificity over the Architect(r) assay in potentially cross-reacting
      samples (94.1 % vs. 82.4 %). The Elecsys IgM assay reported fewer positive
      results in the later stages of CMV infection compared with ETI-CYTOK-M ELISA,
      while the Elecsys IgG assay reported slightly fewer negative results in the early
      stages of infection compared with ETI-CYTOK-G ELISA. There was good agreement
      between Elecsys and comparator assays using unselected clinical samples (range
      90.4-99.4 %). The Elecsys CMV IgM and IgG assays compare well with routinely used
      assays and are suitable for clinical use.

PMID- 22850742
TI  - A chemically unlocked binary molecular switch.
AB  - A highly luminescent and sensitive terbium complex of a ligand comprising of a
      phthalimide group appended to a DO3A moiety is an active pH sensor that is
      conditional on its previous pH.

PMID- 22850743
TI  - Histone dosage regulates DNA damage sensitivity in a checkpoint-independent
      manner by the homologous recombination pathway.
AB  - In eukaryotes, multiple genes encode histone proteins that package genomic
      deoxyribonucleic acid (DNA) and regulate its accessibility. Because of their
      positive charge, 'free' (non-chromatin associated) histones can bind non
      specifically to the negatively charged DNA and affect its metabolism, including
      DNA repair. We have investigated the effect of altering histone dosage on DNA
      repair in budding yeast. An increase in histone gene dosage resulted in enhanced
      DNA damage sensitivity, whereas deletion of a H3-H4 gene pair resulted in reduced
      levels of free H3 and H4 concomitant with resistance to DNA damaging agents, even
      in mutants defective in the DNA damage checkpoint. Studies involving the repair
      of a HO endonuclease-mediated DNA double-strand break (DSB) at the MAT locus show
      enhanced repair efficiency by the homologous recombination (HR) pathway on a
      reduction in histone dosage. Cells with reduced histone dosage experience greater
      histone loss around a DSB, whereas the recruitment of HR factors is concomitantly
      enhanced. Further, free histones compete with the HR machinery for binding to DNA
      and associate with certain HR factors, potentially interfering with HR-mediated
      repair. Our findings may have important implications for DNA repair, genomic
      stability, carcinogenesis and aging in human cells that have dozens of histone
      genes.

PMID- 22850744
TI  - The histone demethylase PHF8 is essential for cytoskeleton dynamics.
AB  - PHF8 is a histone demethylase associated with X-linked mental retardation. It has
      been described as a transcriptional co-activator involved in cell cycle
      progression, but its physiological role is still poorly understood. Here we show
      that PHF8 controls the expression of genes involved in cell adhesion and
      cytoskeleton organization such as RhoA, Rac1 and GSK3beta. A lack of PHF8 not
      only results in a cell cycle delay but also in a disorganized actin cytoskeleton
      and impaired cell adhesion. Our data demonstrate that PHF8 directly regulates the
      expression of these genes by demethylating H4K20me1 at promoters. Moreover, c-Myc
      transcription factor cooperates with PHF8 to regulate the analysed promoters.
      Further analysis in neurons shows that depletion of PHF8 results in down
      regulation of cytoskeleton genes and leads to a deficient neurite outgrowth.
      Overall, our results suggest that the mental retardation phenotype associated
      with loss of function of PHF8 could be due to abnormal neuronal connections as a
      result of alterations in cytoskeleton function.

PMID- 22850745
TI  - Deoxycytidine kinase regulates the G2/M checkpoint through interaction with
      cyclin-dependent kinase 1 in response to DNA damage.
AB  - Deoxycytidine kinase (dCK) is a rate limiting enzyme critical for phosphorylation
      of endogenous deoxynucleosides for DNA synthesis and exogenous nucleoside
      analogues for anticancer and antiviral drug actions. dCK is activated in response
      to DNA damage; however, how it functions in the DNA damage response is largely
      unknown. Here, we report that dCK is required for the G2/M checkpoint in response
      to DNA damage induced by ionizing radiation (IR). We demonstrate that the ataxia
      telangiectasia-mutated (ATM) kinase phosphorylates dCK on Serine 74 to activate
      it in response to DNA damage. We further demonstrate that Serine 74
      phosphorylation is required for initiation of the G2/M checkpoint. Using mass
      spectrometry, we identified a protein complex associated with dCK in response to
      DNA damage. We demonstrate that dCK interacts with cyclin-dependent kinase 1
      (Cdk1) after IR and that the interaction inhibits Cdk1 activity both in vitro and
      in vivo. Together, our results highlight the novel function of dCK and provide
      molecular insights into the G2/M checkpoint regulation in response to DNA damage.

PMID- 22850749
TI  - Coordination chemistry strategies for dynamic helicates: time-programmable
      chirality switching with labile and inert metal helicates.
AB  - 'Chirality switching' is one of the most important chemical processes controlling
      many biological systems. DNAs and proteins often work as time-programmed
      functional helices, in which specific external stimuli alter the helical
      direction and tune the time scale of subsequent events. Although a variety of
      organic foldamers and their hybrids with natural helices have been developed, we
      highlight coordination chemistry strategies for development of structurally and
      functionally defined metal helicates. These metal helicates have characteristic
      coordination geometries, redox reactivities and spectroscopic/magnetic properties
      as well as complex chiralities. Several kinds of inert metal helicates maintain
      rigid helical structures and their stereoisomers are separable by optical
      resolution techniques, while labile metal helicates offer dynamic inversion of
      their helical structures via non-covalent interactions with external chemical
      signals. The latter particularly have dynamically ordered helical structures,
      which are controlled by the combinations of metal centres and chiral ligands.
      They further function as time-programmable switches of chirality-derived dynamic
      rotations, translations, stretching and shape flipping, which are useful
      applications in nanoscience and related technology.

PMID- 22850746
TI  - 2'-Deoxyriboguanylurea, the primary breakdown product of 5-aza-2'
      deoxyribocytidine, is a mutagen, an epimutagen, an inhibitor of DNA
      methyltransferases and an inducer of 5-azacytidine-type fragile sites.
AB  - 5-Aza-2'-deoxycytidine (5azaC-dR) has been employed as an inhibitor of DNA
      methylation, a chemotherapeutic agent, a clastogen, a mutagen, an inducer of
      fragile sites and a carcinogen. However, its effects are difficult to quantify
      because it rapidly breaks down in aqueous solution to the stable compound 2'
      deoxyriboguanylurea (GuaUre-dR). Here, we used a phosphoramidite that permits the
      introduction of GuaUre-dR at defined positions in synthetic oligodeoxynucleotides
      to demonstrate that it is a potent inhibitor of human DNA methyltransferase 1
      (hDNMT1) and the bacterial DNA methyltransferase (M.EcoRII) and that it is a
      mutagen that can form productive base pairs with either Guanine or Cytosine. Pure
      GuaUre-dR was found to be an effective demethylating agent and was able to induce
      5azaC-dR type fragile sites FRA1J and FRA9E in human cells. Moreover, we report
      that demethylation associated with C:G -> G:C transversion and C:G -> T:A
      transition mutations was observed in human cells exposed to pure GuaUre-dR. The
      data suggest that most of the effects attributed to 5azaC-dR are exhibited by its
      stable primary breakdown product.

PMID- 22850750
TI  - Targeted therapies: the toxic reality of new drugs.

PMID- 22850753
TI  - Cell signalling: Stuck in the middle of chemoresistance and metastasis.

PMID- 22850754
TI  - Urological cancer: Radical lessons learnt from the prostate cancer PIVOT trial.

PMID- 22850751
TI  - Overcoming implementation challenges of personalized cancer therapy.
AB  - Personalized cancer therapy is based on the precept that detailed molecular
      characterization of the patient's tumour and its microenvironment will enable
      tailored therapies to improve outcomes and decrease toxicity. The goal of
      personalized therapy is to target aberrations that drive tumour growth and
      survival, by administering the right drug combination for the right person. This
      is becoming increasingly achievable with advances in high-throughput technologies
      to characterize tumours and the expanding repertoire of molecularly targeted
      therapies. However, there are numerous challenges that need to be surpassed
      before delivering on the promise of personalized cancer therapy. These include
      tumour heterogeneity and molecular evolution, costs and potential morbidity of
      biopsies, lack of effective drugs against most genomic aberrations, technical
      limitations of molecular tests, and reimbursement and regulatory hurdles.
      Critically, the 'hype' surrounding personalized cancer therapy must be tempered
      with realistic expectations, which, today, encompass increased survival times for
      only a portion of patients.

PMID- 22850755
TI  - Haematological cancer: Redefining myeloma.

PMID- 22850752
TI  - Cancer prevention by targeting angiogenesis.
AB  - Healthy individuals can harbour microscopic tumours and dysplastic foci in
      different organs in an undetectable and asymptomatic state for many years. These
      lesions do not progress in the absence of angiogenesis or inflammation. Targeting
      both processes before clinical manifestation can prevent tumour growth and
      progression. Angioprevention is a chemoprevention approach that interrupts the
      formation of new blood vessels when tumour cell foci are in an indolent state.
      Many efficacious chemopreventive drugs function by preventing angiogenesis in the
      tumour microenvironment. Blocking the vascularization of incipient tumours should
      maintain a dormancy state such that neoplasia or cancer exist without disease.
      The current limitations of antiangiogenic cancer therapy may well be related to
      the use of antiangiogenic agents too late in the disease course. In this Review,
      we suggest mechanisms and strategies for using antiangiogenesis agents in a safe,
      preventive clinical angioprevention setting, proposing different levels of
      clinical angioprevention according to risk, and indicate potential drugs to be
      employed at these levels. Finally, angioprevention may go well beyond cancer in
      the prevention of a range of chronic disorders where angiogenesis is crucial,
      including different forms of inflammatory or autoimmune diseases, ocular
      disorders, and neurodegeneration.

PMID- 22850756
TI  - Experiences of adult stroke survivors and their parent carers: a qualitative
      study.
AB  - OBJECTIVE: To explore the experiences of adult stroke survivors and their parent
      carers. DESIGN: Qualitative methodology: interpretative phenomenological
      analysis. SETTING: Six residential areas across England and south Wales.
      PARTICIPANTS: Six adult stroke survivors (aged 27-46), six mothers (aged 59-76)
      and five fathers (aged 55-76). METHOD: Semi-structured interviews to explore the
      relationship and interactions between parent and survivor prior to and after a
      stroke, with opportunities to explore both positive and negative changes. All
      interviews were transcribed and analysed by a six step interpretative
      phenomenological analysis process. Survivors, mothers and fathers were analysed
      as three separate groups and the results were synthesised. RESULTS: Identical and
      interconnected themes emerged from the three groups, permitting synthesis into a
      single organising framework with four superordinate themes capturing the key
      issues for all three groups. The four superordinate themes were: 'emotional
      turmoil'; 'significance of parents'; 'negotiating independence versus dependence'
      and 'changed relationships'. CONCLUSIONS: Parents reported adjusting to caring
      with relative ease. Survivors did not adjust to being cared for with such ease
      and felt positioned in a child role. Balancing independence and dependence was a
      challenge for survivors and parents and is considered within a systemic theory
      framework. Implications for service developments and guidelines are considered.

PMID- 22850757
TI  - Can a six-week exercise intervention improve gross motor function for non
      ambulant children with cerebral palsy? A pilot randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of a six-week exercise intervention on gross
      motor function for non-ambulant children with cerebral palsy. DESIGN: A parallel
      arm randomized controlled trial. SETTING: Four special schools. PARTICIPANTS:
      Thirty-five children aged 8-17 with bilateral cerebral palsy; Gross Motor
      Function Classification System levels IV-V. METHOD: Participants were randomly
      allocated to a static bike group, a treadmill group or control group.
      Participants in the bike and treadmill groups received exercise training
      sessions, three times weekly for six weeks. The control group received their
      usual care. Blinded assessments were performed at baseline and six weeks and
      followed up at 12 and 18 weeks. OUTCOME MEASURES: Gross Motor Function Measures
      GMFM-66, GMFM-88D and GMFM-88E. RESULTS: At six weeks significant differences
      were found in GMFM-88D scores between the bike group and the control group, and
      the treadmill group and the control group (P < 0.05). The mean change (SD) in
      GMFM-88D score was 5.9 (6.8) for the bike group; 3.7 (4.4) for the treadmill
      group and 0.5 (1.9) for the control group. No significant differences were found
      for GMFM-66 or GMFM-88E scores between the bike group and control group, or the
      treadmill group and control group, although trends of improvement were observed
      for both exercise groups. The improvements observed declined during the follow-up
      period. CONCLUSION: This study provides preliminary evidence that exercising on a
      bike or treadmill may provide short-term improvements in gross motor function for
      non-ambulant children with cerebral palsy. This needs to be tested in a large
      scale randomized trial.

PMID- 22850758
TI  - Flow cytometry analysis of cancer cell death induced by the extract of Thai plant
      Ellipeiopsis cherrevensis.
AB  - The mechanism of cancer cell death induced by KP018, an ethanol extract of the
      Thai plant Ellipeiopsis cherrevensis, was examined in paclitaxel-resistant HepG2
      (PR-HepG2) and colon-26 cells using flow cytometry. In PR-HepG2 cells, KP018
      induced necrosis in a concentration-dependent manner. Necrosis of PR-HepG2 cells
      induced by KP018 as well as by hydrogen peroxide was suppressed by co-treatment
      of the cells with N-acetylcysteine. KP018 decreased the viability of colon-26
      cells with an IC50 value of 15.1 ug/mL, which was estimated by XTT assay. As
      observed in PR-HepG2 cells, KP018 induced necrosis and the necrosis was
      suppressed by N-acetylcysteine in colon-26 cells. In addition, using colon-26
      solid tumor-bearing mice, KP018 was found to suppress tumor growth without
      apparent toxicities under in vivo conditions. These results indicate that KP018
      induces necrosis rather than apoptosis in these cancer cells, and reactive oxygen
      species such as hydrogen peroxide would be involved in KP018-induced necrosis.
      KP018 may be a useful source to search for a new anticancer drug that can be used
      for the chemotherapy of multidrug-resistant tumors.

PMID- 22850759
TI  - The role of inter-segmental differences in P-glycoprotein expression and activity
      along the rat small intestine in causing the double-peak phenomenon of substrate
      plasma concentration.
AB  - Conflicting results have been reported on segmental differences in expression
      of P-glycoprotein (P-gp) along the small intestine of animals and humans. In this
      study, we investigated P-gp mRNA and protein levels within each of nine segments
      of rat small intestine. In addition, P-gp activity in each segment was evaluated
      in terms of permeability of rhodamine123 (Rho123), a typical P-gp substrate,
      using the serial intestinal non-everted sac method. The P-gp mRNA levels tended
      to increase from the duodenum to the ileum, with peaks in the upper and lower
      ileum, while P-gp protein level reached its maximum in the middle ileum. The
      activity of P-gp was also the highest in the middle ileum, and was highly
      correlated with P-gp protein level. The double-peaked plasma concentration
      profile that was observed following oral administration of Rho123 to rats could
      be well reproduced by an intestinal compartmental kinetic model incorporating
      inter-segmental differences of absorption and excretion rate constants. Our
      results suggest that the heterogeneous distribution of P-gp along the small
      intestine plays a key role in causing the double-peak of plasma concentration of
      P-gp substrates following oral administration to rats.

PMID- 22850760
TI  - Effects of grapefruit juice and SLCO1B1 388A>G polymorphism on the
      pharmacokinetics of pitavastatin.
AB  - Pitavastatin undergoes little hepatic metabolism but it is a substrate for uptake
      and efflux transporters, particularly OATP1B1 (gene SLCO1B1). A previous study in
      8 Japanese healthy subjects showed that co-administration with grapefruit juice
      (GFJ) resulted in a small increase in systemic exposure to pitavastatin. We
      examined whether common polymorphisms in SLCO1B1 might influence the
      pharmacokinetics of pitavastatin or the interaction with GFJ. Twelve Chinese
      healthy male volunteers took pitavastatin 2 mg orally with water or with GFJ on
      separate occasions and plasma concentrations of pitavastatin acid and lactone
      were measured over 48 h. GFJ increased the mean area under the plasma
      concentration-time curve (AUC0-48 h) for both pitavastatin acid and lactone by
      14% (p<0.05). Subjects with SLCO1B1 *1b/*1b haplotype (388GG-521TT) had 47% and
      44% higher systemic exposure for pitavastatin acid and lactone than the SLCO1B1
      *1a carriers (388AA/AG-521TT, p<0.05 and p=0.005, respectively). The SLCO1B1
      388A>G polymorphism, which increases transporter activity for some statins, was
      associated with higher plasma levels of pitavastatin acid and lactone in subjects
      with the homozygous variant indicating decreased hepatic uptake. Co
      administration of pitavastatin with GFJ resulted in a small but significant
      increase in plasma levels in healthy Chinese subjects.

PMID- 22850762
TI  - Retention of nisin activity at elevated pH in an organic acid complex and gold
      nanoparticle composite.
AB  - Biocompatible organic acids and citrate-stabilized gold nanoparticles were
      interacted with nisin to generate robust antimicrobial agents, which display
      archetypical nisin activity even at elevated pH.

PMID- 22850763
TI  - Synthetic approach to flavanones and flavones via ligand-free palladium(II)
      catalyzed conjugate addition of arylboronic acids to chromones.
AB  - The remarkable catalytic effects of Fe(OTf)(3) in the context of the Pd(ii)
      catalyzed conjugate addition of arylboronic acids to chromones were observed to
      yield a variety of flavanones under mild conditions. The addition of catalytic
      amounts of DDQ and KNO(2) to the reactions exclusively yielded flavone analogs.
      The reaction scope for the transformation was fairly broad, affording good yields
      of a wide range of flavanones and flavones, which are privileged structures in
      many biologically active compounds.

PMID- 22850764
TI  - Editorial: to resolve or not to resolve: annexin A1 pushes resolution on track.

PMID- 22850765
TI  - Editorial: protean effects of IL-10 include skin self-defense.

PMID- 22850767
TI  - Powering the future of molecular artificial photosynthesis with light-harvesting
      metallosupramolecular dye assemblies.
AB  - Chemical ingenuity will play a significant role in solving the greatest challenge
      currently facing society: providing clean and carbon neutral energy for all of
      humanity. Molecular artificial photosynthesis is an emerging technology based on
      principles learned from Nature where individual components perform the essential
      light-harvesting, charge-separation, and water splitting functions to store solar
      energy in the form of chemical bonds. This tutorial review focuses specifically
      on the application of metallosupramolecular self-assembly strategies to interface
      solar fuel catalysts with photosensitizers and construct light-harvesting
      antennae capable of achieving panchromatic absorption and directional energy
      concentration.

PMID- 22850768
TI  - Erosive wrist and hand arthritis: is it a rare manifestation of Behcet's disease?
AB  - It is believed that arthritis in Behcet's disease is usually non-erosive and non
      destructive. We report herein a 72-year-old female who presented with Behcet's
      disease and an erosive arthritis of the bilateral elbow, wrist, and
      metacarpophalangeal and proximal interphalangeal joints, radiologically mimicking
      rheumatoid arthritis. 

PMID- 22850770
TI  - DSM-5 and clinical trials in psychiatry: challenges to come?
AB  - The publication of the fifth version of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-5) in 2013 raises important questions for clinical trials
      and associated regulatory decisions on new drugs for psychiatric disorders.

PMID- 22850771
TI  - Overtaking the DILI Model-T.

PMID- 22850772
TI  - PDUFA V goes back to basics.

PMID- 22850775
TI  - Jane Reese-Coulbourne. Interviewed by Asher Mullard.

PMID- 22850776
TI  - Pasireotide.

PMID- 22850777
TI  - Autoimmune disease: Targeting IL-7 reverses type 1 diabetes.

PMID- 22850778
TI  - Metabolic disorders: New target for appetite control.

PMID- 22850779
TI  - Neurodegenerative disorders: Reversing Huntington's disease.

PMID- 22850780
TI  - Cancer: PD1 makes waves in anticancer immunotherapy.

PMID- 22850785
TI  - Anticancer drugs: Antitumour potential of catalytic DNA.

PMID- 22850786
TI  - Revisiting lab-on-a-chip technology for drug discovery.
AB  - The field of microfluidics or lab-on-a-chip technology aims to improve and extend
      the possibilities of bioassays, cell biology and biomedical research based on the
      idea of miniaturization. Microfluidic systems allow more accurate modelling of
      physiological situations for both fundamental research and drug development, and
      enable systematic high-volume testing for various aspects of drug discovery.
      Microfluidic systems are in development that not only model biological
      environments but also physically mimic biological tissues and organs; such
      'organs on a chip' could have an important role in expediting early stages of
      drug discovery and help reduce reliance on animal testing. This Review highlights
      the latest lab-on-a-chip technologies for drug discovery and discusses the
      potential for future developments in this field.

PMID- 22850788
TI  - Strong presence of the high grain protein content allele of NAM-B1 in
      Fennoscandian wheat.
AB  - Grain protein content in wheat has been shown to be affected by the NAM-B1 gene
      where the wildtype allele confers high levels of protein and micronutrients but
      can reduce yield. Two known non-functional alleles instead increase yield but
      lead to lower levels of protein and micronutrients. The wildtype allele in
      hexaploid bread wheat is so far mainly known from historical specimens and a few
      lines with an emmer wheat introgression. Here we report a screening for the
      wildtype allele in wheats of different origin. First, a worldwide core collection
      of 367 bread wheats with worldwide origin was screened and five accessions
      carrying the wildtype NAM-B1 allele were found. Several of these could be traced
      to a Fennoscandian origin and the wildtype allele was more frequent in spring
      wheat. These findings, together with the late maturation of spring wheat,
      suggested that the faster maturation caused by the wildtype allele might have
      preserved it in areas with a short growing season. Thus a second set consisting
      of 138 spring wheats of a northern origin was screened and as many as 33 % of the
      accessions had the wildtype allele, all of a Fennoscandian origin. The presence
      of the wildtype allele in landraces and cultivars is in agreement with the use of
      landraces in Fennoscandian wheat breeding. Last, 22 spelt wheats, a wheat type
      previously suggested to carry the wildtype allele, were screened and five
      wildtype accessions found. The wildtype NAM-B1 accessions found could be a
      suitable material for plant breeding efforts directed towards increasing the
      nutrient content of bread wheat.

PMID- 22850789
TI  - Temperature humidity index scenarios in the Mediterranean basin.
AB  - The study was undertaken to describe the temperature humidity index (THI)
      dynamics over the Mediterranean basin for the period 1971-2050. The THI combines
      temperature and humidity into a single value, and has been widely used to predict
      the effects of environmental warmth in farm animals. The analysis was based on
      daily outputs of the temperature and relative humidity from the Max Planck
      Institute data using the Intergovernmental Panel on Climate Change Special Report
      Emission Scenario A1B. Data revealed a gradual increase of both annual and
      seasonal THI during the period under investigation and a strong heterogeneity of
      the Mediterranean area. In particular, the analysis indicated that Spain,
      southern France and Italy should be expected to undergo the highest THI increase,
      which in the last decade under study (2041-2050) will range between 3 and 4
      units. However, only during summer months the area presents characteristics
      indicating risk of thermal (heat) stress for farm animals. In this regard,
      scenario maps relative to the summer season suggested an enlargement of the areas
      in the basin where summer THI values will likely cause thermal discomfort in farm
      animals. In conclusion, the study indicated that the Mediterranean basin is
      likely to undergo THI changes, which may aggravate the consequences of hot
      weather on animal welfare, performances, health and survival and may help
      farmers, nutritionists, veterinarians, and policy-makers to develop appropriate
      adaptation strategies to limit consequences of climate change for the livestock
      sector in the Mediterranean countries.

PMID- 22850790
TI  - Type II thioesterase gene (ECO-orf27) from Amycolatopsis orientalis influences
      production of the polyketide antibiotic, ECO-0501 (LW01).
AB  - ECO-orf27 associated with the cluster of ECO-0501 (LW01) from Amycolatopsis
      orientalis is deduced to encode a type II thioesterase. Disruption of ECO-orf27
      reduced LW01 production by 95 %. Complementation of the disrupted mutant with
      intact ECO-orf27 restored the production of LW01 suggesting that ECO-orf27 is
      crucial for LW01 biosynthesis. ECO-TE I, the gene encoding type I thioesterase
      from LW01 polyketide synthases, cannot complement ECO-orf27 deficient mutant
      distinguishing ECO-orf27 from type I thioesterase gene. Type II thioesterase gene
      pikAV from Streptomyces venezuelae could complement ECO-orf27 in A. orientalis
      indicating that the two genes are equivalent in their function. Overexpression of
      ECO-orf27 resulted in a 20 % increase in LW01 production providing an alternative
      approach for yield improvement.

PMID- 22850791
TI  - Plant beta-1,3-glucanases: their biological functions and transgenic expression
      against phytopathogenic fungi.
AB  - beta-1,3-Glucanases are abundant in plants and have been characterized from a
      wide range of species. They play key roles in cell division, trafficking of
      materials through plasmodesmata, in withstanding abiotic stresses and are
      involved in flower formation through to seed maturation. They also defend plants
      against fungal pathogens either alone or in association with chitinases and other
      antifungal proteins. They are grouped in the PR-2 family of pathogenesis-related
      (PR) proteins. Use of beta-1,3-glucanase genes as transgenes in combination with
      other antifungal genes is a plausible strategy to develop durable resistance in
      crop plants against fungal pathogens. These genes, sourced from alfalfa, barley,
      soybean, tobacco, and wheat have been co-expressed along with other antifungal
      proteins, such as chitinases, peroxidases, thaumatin-like proteins and alpha-1
      purothionin, in various crop plants with promising results that are discussed in
      this review.

PMID- 22850787
TI  - Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases.
AB  - Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers
      pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in
      autoinflammatory syndromes results in a rapid and sustained reduction in disease
      severity, including reversal of inflammation-mediated loss of sight, hearing and
      organ function. This approach can therefore be effective in treating common
      conditions such as post-infarction heart failure, and trials targeting a broad
      spectrum of new indications are underway. So far, three IL-1-targeted agents have
      been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor
      rilonacept and the neutralizing monoclonal anti-IL-1beta antibody canakinumab. In
      addition, a monoclonal antibody directed against the IL-1 receptor and a
      neutralizing anti-IL-1alpha antibody are in clinical trials.

PMID- 22850792
TI  - Modeling the association between particle constituents of air pollution and
      health outcomes.
AB  - There is increasing interest in evaluating the association between specific fine
      particle (particles with aerodynamic diameters less than 2.5 um; PM2.5)
      constituents and adverse health outcomes rather than focusing solely on the
      impact of total PM2.5. Because PM2.5 may be related to both constituent
      concentration and health outcomes, constituents that are more strongly correlated
      with PM2.5 may appear more closely related to adverse health outcomes than other
      constituents even if they are not inherently more toxic. Therefore, it is
      important to properly account for potential confounding by PM2.5 in these
      analyses. Usually, confounding is due to a factor that is distinct from the
      exposure and outcome. However, because constituents are a component of PM2.5,
      standard covariate adjustment is not appropriate. Similar considerations apply to
      source-apportioned concentrations and studies assessing either short-term or long
      term impacts of constituents. Using data on 18 constituents and data from 1,060
      patients admitted to a Boston medical center with ischemic stroke in 2003-2008,
      the authors illustrate several options for modeling the association between
      constituents and health outcomes that account for the impact of PM2.5. Although
      the different methods yield results with different interpretations, the relative
      rankings of the association between constituents and ischemic stroke were fairly
      consistent across models.

PMID- 22850793
TI  - Re: "credible mendelian randomization studies: approaches for evaluating the
      instrumental variable assumptions".

PMID- 22850794
TI  - Re: "credible mendelian randomization studies: approaches for evaluating the
      instrumental variable assumptions".

PMID- 22850795
TI  - Re: "dealing with missing outcome data in randomized trials and observational
      studies".

PMID- 22850796
TI  - Architectures, mechanisms and molecular evolution of natural product
      methyltransferases.
AB  - The addition of a methyl moiety to a small chemical is a common transformation in
      the biosynthesis of natural products across all three domains of life. These
      methylation reactions are most often catalysed by S-adenosyl-L-methionine (SAM)
      dependent methyltransferases (MTs). MTs are categorized based on the electron
      rich, methyl accepting atom, usually O, N, C, or S. SAM-dependent natural product
      MTs (NPMTs) are responsible for the modification of a wide array of structurally
      distinct substrates, including signalling and host defense compounds, pigments,
      prosthetic groups, cofactors, cell membrane and cell wall components, and
      xenobiotics. Most notably, methylation modulates the bioavailability,
      bioactivity, and reactivity of acceptor molecules, and thus exerts a central role
      on the functional output of many metabolic pathways. Our current understanding of
      the structural enzymology of NPMTs groups these phylogenetically diverse enzymes
      into two MT-superfamily fold classes (class I and class III). Structural biology
      has also shed light on the catalytic mechanisms and molecular bases for substrate
      specificity for over fifty NPMTs. These biophysical-based approaches have
      contributed to our understanding of NPMT evolution, demonstrating how a
      widespread protein fold evolved to accommodate chemically diverse methyl
      acceptors and to catalyse disparate mechanisms suited to the physiochemical
      properties of the target substrates. This evolutionary diversity suggests that
      NPMTs may serve as starting points for generating new biocatalysts.

PMID- 22850797
TI  - Medium-sized and strained heterocycles from non-catalysed and gold-catalysed
      conversions of beta-carbolines.
AB  - 2-Allyl-1-vinyl-beta-carbolines and dihydropyrrolo-beta-carbolines react with
      activated internal alkynes through novel rearrangement reactions leading to
      complex polycyclic structures. Favored reaction pathways depend on reaction
      conditions and on the presence of gold catalysts. In particular, upon reaction
      with 2 equiv. of the alkyne, new hexacyclic structures 10 are formed with total
      stereocontrol.

PMID- 22850798
TI  - Improving the quality of qualitative studies: do reporting guidelines have a
      place?

PMID- 22850799
TI  - Retraction.

PMID- 22850802
TI  - An aerobic walking programme versus muscle strengthening programme for chronic
      low back pain: a randomized controlled trial.
AB  - OBJECTIVE: To assess the effect of aerobic walking training as compared to active
      training, which includes muscle strengthening, on functional abilities among
      patients with chronic low back pain. DESIGN: Randomized controlled clinical trial
      with blind assessors. SETTING: Outpatient clinic. SUBJECTS: Fifty-two sedentary
      patients, aged 18-65 years with chronic low back pain. Patients who were post
      surgery, post trauma, with cardiovascular problems, and with oncological disease
      were excluded. INTERVENTION: Experimental 'walking' group: moderate intense
      treadmill walking; control 'exercise' group: specific low back exercise; both,
      twice a week for six weeks. MAIN MEASURES: Six-minute walking test, Fear
      Avoidance Belief Questionnaire, back and abdomen muscle endurance tests, Oswestry
      Disability Questionnaire, Low Back Pain Functional Scale (LBPFS). RESULTS:
      Significant improvements were noted in all outcome measures in both groups with
      non-significant difference between groups. The mean distance in metres covered
      during 6 minutes increased by 70.7 (95% confidence interval (CI) 12.3-127.7) in
      the 'walking' group and by 43.8 (95% CI 19.6-68.0) in the 'exercise' group. The
      trunk flexor endurance test showed significant improvement in both groups,
      increasing by 0.6 (95% CI 0.0-1.1) in the 'walking' group and by 1.1 (95% CI 0.3
      1.8) in the 'exercise' group. CONCLUSIONS: A six-week walk training programme was
      as effective as six weeks of specific strengthening exercises programme for the
      low back.

PMID- 22850801
TI  - Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood
      derived mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have the ability to migrate into tumors
      and therefore are potential vehicles for the therapy of malignant diseases. In
      this study, we investigated the use of umbilical cord blood mesenchymal stem
      cells (UCB-MSCs) as carriers for a constant source of transgenic LIGHT (TNFSF14)
      to target tumor cells in vivo. METHODS: Lentiviral vectors carrying LIGHT genes
      were constructed, producing viral particles with a titer of 2 * 10(8) TU/L.
      Fourteen days after UCB-MSCs transfected by LIGHT gene packaged lentivirus had
      been injected into mouse gastric cancer models, the expression levels of LIGHT
      mRNA and protein were detected by reverse transcription polymerase chain reaction
      (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Then the tumors'
      approximate volumes were measured. RESULTS: The treatment with MSC-LIGHT
      demonstrated a strong suppressive effect on tumor growth compared to treatment
      with MSC and NaCl (p < 0.001). Examination of pathological sections of the tumor
      tissues showed that the areas of tumor necrocis in the MSC-LIGHT group were
      larger than those in the MSC group. Moreover, we found that MSCs with LIGHT were
      able to significantly induce apoptosis of tumor cells. The expression levels of
      LIGHT mRNA and protein were significantly higher in the UCB-MSCs with the LIGHT
      gene than the levels in UCB-MSCs (p < 0.001). CONCLUSION: These results suggest
      that UCB-MSCs carrying the LIGHT gene have the potential to be used as effective
      delivery vehicles in the treatment of gastric cancers.

PMID- 22850803
TI  - Catalytic hyperbranched polymers as enzyme mimics; exploiting the principles of
      encapsulation and supramolecular chemistry.
AB  - Nature uses the principles of encapsulation and supramolecular chemistry to bind
      and orientate substrates within active catalytic sites. Over the years, synthetic
      chemistry has generated a number of small molecule active site mimics capable of
      catalysing reactions involving bound substrates. Another approach uses larger
      molecules that better represent an enzymes globular structure. These molecules
      mimic an enzymes structure by incorporating binding/catalytic sites within the
      globular structure of the polymer. As such, the electronic and steric properties
      around the binding/catalytic site(s) can be controlled and fine-tuned. One class
      of polymer that is particularly adept at mimicking the globular structure of
      enzymes are dendritic polymers. This review will concentrate on the use of
      hyperbranched polymers as synthetic enzyme mimics.

PMID- 22850804
TI  - Cancer prevention for global health: a report from the ASPO International Cancer
      Prevention Interest Group.
AB  - As cancer incidence and mortality rates increase in low- and middle-income
      countries, the need for cancer prevention and control research directed to these
      countries becomes increasingly important. The American Society of Preventive
      Oncology (ASPO) is a community of professionals in cancer prevention and control
      whose mission is to "foster the continuing development of investigators and the
      exchange and translation of scientific information to reduce the cancer burden."
      In the session presented at the ASPO 36th Annual Meeting in Washington, DC in
      March 2012, chaired by Drs. Frank Meyskens and Dejana Braithwaite, Dr. Paolo
      Boffetta discussed some of the achievements in global cancer prevention and
      suggested that future efforts focus on three major causes of cancer: tobacco-use,
      infections, and overweight/obesity. Dr. Timothy Rebbeck presented an overview of
      prostate cancer research in sub-Saharan Africa and highlighted how the complex
      nature of prostate cancer etiology and outcomes can be addressed through capacity
      building research partnerships. Cancer is an emerging public health challenge in
      developing countries because of the aging and expansion of the population and
      increased prevalence of cancer risk factors such as smoking, obesity, physical
      inactivity, and reproductive factors. There are opportunities to reduce the
      growing cancer burden through the development of research capacity and the
      application of resource-appropriate interventions.

PMID- 22850805
TI  - Serum prostate-specific antigen concentration and hemodilution among Chinese
      middle-aged obese men: a hematocrit-based equation for plasma volume estimation
      is induced.
AB  - BACKGROUND: A hematocrit (HCT)-based and a body surface area (BSA)-based
      equations were applied for plasma volume (PV) estimation, respectively, to
      confirm and quantify the hemodilution effect in prostate-specific antigen (PSA)
      screening among obese men. The agreement between the equations was additionally
      investigated. METHODS: A total of 1,444 men were retrospectively collected, with
      ages 40 to 65 years, PSA 0 to 4 ng/mL, and no prostate cancer. PSA mass was
      calculated as PSA concentration multiplied by PV. Multivariable linear regression
      models, theoretical models, and the Bland-Altman method were used. RESULTS: PSA
      concentration significantly decreased with increasing body mass index (BMI; beta
      = -0.011, P < 0.001); however, PSA mass estimated by HCT- (beta = 0.004, P =
      0.132) and BSA (beta = -0.003, P = 0.094)-based equations remained consistent. A
      screening PSA of 4.0 ng/mL in nonobese men was found to be corresponding to 3.32
      and 3.68 ng/mL in obese men extrapolated by PV on the basis of HCT and BSA,
      respectively. Moreover, the mean (95% confidence interval) difference of PV
      between the two equations was 0.33 (-0.06 to 0.73) L. CONCLUSIONS: The inverse
      relationship between PSA concentration and BMI might be explained by a
      hemodilution effect among obese men. There is significant variation in PV
      calculated by the two equations. IMPACT: A value between 3.32 and 3.68 ng/mL
      might be recommended for PSA screening in middle-aged obese Asian men.

PMID- 22850806
TI  - Do breast implants adversely affect prognosis among those subsequently diagnosed
      with breast cancer? Findings from an extended follow-up of a Canadian cohort.
AB  - BACKGROUND: Cosmetic breast implants may impair the ability to detect breast
      cancers. The aims of this study were to examine whether implants and implant
      characteristics are associated with more advanced breast tumors at diagnosis and
      poorer survival. METHODS: Study population includes all invasive breast cancer
      cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A
      total of 409 women with cosmetic breast implants and 444 women with other
      cosmetic surgery were diagnosed with breast cancer. These women were compared for
      stage at diagnosis using multinomial logistic regression models. Cox proportional
      hazards regression models were used for breast cancer-specific mortality
      analyses. Comparisons were also conducted according to implant characteristics.
      RESULTS: Compared with women with other cosmetic surgery, those with cosmetic
      breast implants had at later stage breast cancer diagnosis (OR of having stage
      III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81-5.10; P
      < 0.001). A nonstatistically significant increase in breast cancer-specific
      mortality rate for women with breast implants relative to surgical controls was
      observed (HR = 1.32, 95% CI: 0.94-1.83, P = 0.11). No statistically significant
      differences in stage and breast cancer mortality were observed according to
      implant characteristics. CONCLUSIONS: At diagnosis, breast cancers tended to be
      at more advanced stages among women with cosmetic breast implants. Breast cancer
      specific survival was lower in these women although the reduction did not reach
      statistical significance. IMPACT: Further investigations of the effect of breast
      implants on breast cancer prognosis are warranted.

PMID- 22850808
TI  - Revealing non-covalent interactions in solids: NCI plots revisited.
AB  - In this article, the NCI method [Johnson et al., J. Am. Chem. Soc., 2010, 132,
      6498] for plotting and analysing non-covalent interactions (NCI) is extended to
      periodic (solid-state) electron densities and implemented in the critic program.
      The new code uses self-consistent electron densities from a variety of electronic
      structure methods (pseudopotentials/plane-wave, FP-LAPW, local orbitals, etc.),
      and it can also build the promolecular density from the crystal geometry alone.
      As an example of the new code, intermolecular interactions in several molecular
      crystals are presented and analyzed. The connection with QTAIM studies is
      established and a reinterpretation of the NCI domains is given regarding the
      current knowledge of the field. The connection between NCI domains and
      intermolecular vibrations is made apparent, as well as the ability of the method
      to reveal the locality of bonding.

PMID- 22850807
TI  - Children and adolescents with ureteropelvic junction obstruction: is an
      additional voiding cystourethrogram necessary? Results of a multicenter study.
AB  - PURPOSE: The incidence of ureteropelvic junction obstruction (UPJO) and
      concomitant vesicoureteral reflux (VUR) ranges from 14 to 18 %. Therefore,
      different guidelines recommend a voiding cystourethrogram (VCUG) to identify
      cases of VUR early in the diagnostic process. Aim of this multicenter study was
      to reassess the incidence of concomitant VUR and the need for additional VCUG in
      a large cohort of patients with UPJO. Furthermore, we asked for clinical
      objectives that defined the need for VCUG with the intention of minimizing
      radiation exposure and the need for invasive diagnostic procedures. METHODS:
      Medical records for 266 patients (69 girls, 197 boys) with UPJO were analyzed
      retrospectively. Data were obtained on gender, clinical symptoms, results of pre-
      and postnatal ultrasound, VCUG and 99(m)Technetium-MAG3 (MAG3) scan. They were
      correlated with the incidence of concomitant VUR. RESULTS: One hundred and
      seventy-eight patients (67 %) underwent VCUG. Concomitant VUR was detected in 13
      patients. Dilating VUR (dVUR) was observed in 11 patients. In our study, the
      overall incidence of a concomitant VUR was 7.3 %. In cases of proven VUR, we
      observed a positive predictive value for female gender, ureteral dilatation,
      renal insufficiency, and recurrent urinary tract infections (UTI). But there was
      no correlation between concomitant VUR and the severity of hydronephrosis.
      CONCLUSIONS: Our data suggest that the low incidence of concomitant VUR in cases
      of UPJO does not justify the routine use of VCUG as a routine diagnostic tool.
      Especially, ureteral dilatation and recurrent UTI have a positive predictive
      value for concomitant VUR.

PMID- 22850809
TI  - Changes of growth, photosynthesis and alteration of leaf antioxidative defence
      system of tea [Camellia sinensis (L.) O. Kuntze] seedlings under aluminum stress.
AB  - Tea [Camellia sinensis (L.) O. Kuntze] is an aluminum (Al) hyperaccumulator plant
      and is commercially important due to its high content of antioxidants. Although
      Al induced growth is well-known for the plants growing in acid soil, yet the
      cause underlying the stimulatory effect of Al has not been fully understood. To
      investigate the possible role of Al in growth induction, we studied
      morphological, physiological as well as biochemical changes of tea plant under
      different Al concentrations (0-4,000 MUM). In hydroponics, Al (15 MUM), enhanced
      shoot and root growth, but at higher concentrations, it caused oxidative damage
      which culminated in a cascade of biochemical changes, Al content increased
      concurrently with the maturity of the leaf as well as stem tissues than their
      younger counterparts. Hematoxylin staining indicated that Al accumulation started
      after 6 h of exposure in the tips of young roots and accumulation was dose
      dependent. The physiological parameters such as pigments, photosynthetic rate,
      transpiration and stomatal conductance were declined due to Al toxicity.
      Alteration in activated oxygen metabolism was also evidenced by increasing lipid
      peroxidation, membrane injury, evolution of superoxide anions and accumulation of
      H(2)O(2). Contents of phenols initially exhibited an acceleration which gradually
      plummeted at higher levels whereas total sugar and starch contents decimated
      beyond 15 MUM of Al concentration. Activities of antioxidant defense enzymes were
      increased with the elevated concentration of Al. Expression of citrate synthase
      gene was up-regulated in the mature leaves, young as well as old roots
      simultaneously with increased concentration of Al in those parts; indicating the
      formation of Al-citrate complex. These results cooperatively specified that Al
      concentration at lower level promoted growth but turned out to be a stressor at
      elevated stages indicating the sensitivity of the cultivar (T-78) to Al.

PMID- 22850810
TI  - The evaluation of bone mineral density in patients with nonalcoholic fatty liver
      disease.
AB  - BACKGROUND AND AIM: Nonalcoholic fatty liver diseases (NAFLD) are a clinical
      spectrum of disorders, of which nonalcoholic steatohepatitis (NASH) is the most
      strongly associated with inflammation. Inflammation is a known risk factor for
      low bone mass in the body. The primary goal of the present study was to evaluate
      the association between bone mineral density and liver function in patients with
      NASH. MATERIALS AND METHODS: Consenting patients with a diagnosis of NAFLD were
      included in the study. Extent of fatty change was graded based on
      ultrasonographic appearance (Grade 1, mild; Grade 2, moderate; Grade 3, severe).
      Bone mineral density was measured using the dual-energy x-ray absorptiometry
      method. ALT and hs-CRP were considered as noninvasive marker of NASH. According
      to ALT levels, patients were divided into two subgroups. RESULTS: A total of 102
      patients with NAFLD and 54 healthy controls participated in the study. None of
      the patients with NAFLD had an abnormal bone mineral density. Furthermore, there
      was no difference between groups with regard to serum vitamin D levels. A
      subgroup analysis revealed that female patients with elevated serum ALT level had
      significantly lower bone mineral densities and higher hsCRP levels than female
      patients with normal ALT levels. The difference in vitamin D levels and body mass
      indices between the same subgroups was statistically insignificant. CONCLUSIONS:
      Simple steatosis of the liver does not affect bone mineral density. However, in a
      subgroup of patients with NAFLD, the presence of elevated serum ALT and hs-CRP
      levels, which are suggestive of NASH, was associated with lower bone mineral
      densities. Better understanding of the biological basis and the complex
      interactions between NAFLD and bone mass may help guide the clinical management
      of bone diseases associated with inflammation of the liver.

PMID- 22850811
TI  - Central venous to arterial pCO2 difference in cardiogenic shock.
AB  - In normal circumstances central venous to arterial pCO(2) difference is
      approximately 1 kPa (7.5 mmHg). In shock states it is usually increased. We
      sought to evaluate the agreement between admission central venous to arterial
      pCO(2) difference and mortality in patients with acute myocardial infarction and
      cardiogenic shock. We hypothesized that patients with higher central venous to
      arterial pCO(2) difference on admission would have higher mortality. We
      retrospectively included 30 patients with acute myocardial infarction and
      cardiogenic shock (mean age 67 +/- 10 years, 73 % men), of which 20 (67 %) died.
      Nonsignificant differences between survivors and nonsurvivors were observed in
      age, gender, admission mean blood pressure, heart rate, lactate, hemoglobin, peak
      troponin I, cardiopulmonary resuscitation, use of therapeutic hypothermia,
      vasopressors, inotropes, intraaortic balloon pump, and mechanical ventilation. A
      significant difference between survivors and nonsurvivors was observed in
      admission central venous to arterial pCO(2) difference (1.35 +/- 0.49 kPa vs.
      0.83 +/- 0.36 kPa, p = 0.003). In patients with admission central venous oxygen
      saturation over 70 %, we observed a significant difference in central venous to
      arterial pCO(2) difference between survivors and nonsurvivors (1.33 +/- 0.51 kPa
      vs. 0.7 +/- 0.3 kPa, p = 0.003) and a nonsignificant difference between survivors
      and nonsurvivors in patients with admission central venous oxygen saturation
      under 70 % (1.38 +/- 0.53 kPa vs. 1.25 +/- 0.33 kPa, p = 0.37). Patients with
      decreased central venous to arterial pCO(2) difference on admission seem to be at
      increased risk of dying even with admission central venous oxygen saturation over
      70 %.

PMID- 22850812
TI  - Neoadjuvant radiotherapy of head and neck carcinoma: an obstacle for plastic
      reconstruction?
AB  - Head and neck carcinomas often are at an advanced stage at the time of diagnosis
      and therefore frequently primarily hardly operable. A downstaging achieved by
      neoadjuvant radiotherapy can facilitate a radical tumor resection. Because of
      radiogenic tissue alterations like scarring and impairment of blood supply,
      elaborate operations, such as microsurgical reconstructions, are aggravated to a
      degree, and most surgeons consider them impossible. In this paper, we report our
      experiences with plastic-surgical reconstruction in patients with neoadjuvant
      pretreated head and neck carcinoma.In the last 6 years, eight patients with an
      advanced head and neck carcinoma were subjected to neoadjuvant radiotherapy
      followed by a radical tumor resection and reconstruction within the same session.
      Therefore, pedicled pectoralis flaps (in three patients), microvascular radialis
      flaps (two), lateral upper arm flaps (one), parascapular flaps (one), and a
      microsurgical anastomosed jejunal graft were used. The mean follow-up period was
      44.5 months.The surgical postoperative course was uneventful in 75 % of patients
      (six out of eight). An anastomosis venous thrombose in one patient and a wound
      dehiscence in another required revision. In the end, a satisfactory result could
      be achieved in all the patients.Sophisticated reconstructions in irritated
      patients with ENT carcinoma are challenging; therefore, efficient
      interdisciplinary cooperation can overcome this obstacle.

PMID- 22850815
TI  - Nitrofurantoin-induced life-threatening seizures.

PMID- 22850814
TI  - Subinvolution of placental bed vessels: case report and review of the literature.
AB  - Subinvolution of placental bed vessels, a well-recognized cause of postpartum and
      postabortal hemorrhage, is defined with prolonged or excessive uterine hemorrhage
      beginning after the delivery or abortion. Although physiological changes in
      uteroplacental parts of spiral arteries are well known, the sequence of events in
      involution of these vessels is not yet clearly understood. In this article we
      present two cases of subinvolution of placental bed vessels in which we were able
      to demonstrate the presence of extravillous trophoblast in and around the
      placental bed vessels. The disease is supposed to be the result of abnormal
      interaction between maternal uterine cells and fetal trophoblast.

PMID- 22850817
TI  - Technologies: Seeing ubiquitin chains.

PMID- 22850818
TI  - Cell signalling: A necrosome build-up.

PMID- 22850820
TI  - Regioselective synthesis of 2-(2-hydroxyaryl)pyridines from the reactions of
      benzynes with pyridine N-oxides.
AB  - By modifying the conditions from those in Larock's reported synthesis of 3-(2
      hydroxyaryl)pyridines from benzynes, and pyridine N-oxides, we altered the
      regioselectivity of the reaction toward an efficient synthesis of 2-substituted
      pyridines. The presence of ethyl propiolate altered the regioselectivity to
      afford 3-substituted pyridine products instead. We conducted appropriate control
      experiments that enable a full understanding of the mechanism.

PMID- 22850821
TI  - The definition of healthcare-associated pneumonia (HCAP) is insufficient for the
      medical environment in Japan: a comparison of HCAP and nursing and healthcare
      associated pneumonia (NHCAP).
AB  - Healthcare-associated pneumonia (HCAP) is a new concept of pneumonia, which was
      proposed in the ATS/IDSA guidelines. The guidelines explain that HCAP patients
      should be treated with broad-spectrum antimicrobial drugs directed at multidrug
      resistant pathogens. However, in Japan, there are many elderly people who
      received in-home care service. These patients seemed to be consistent with the
      concept of HCAP, but they did not meet the definition of HCAP. Therefore, the
      Japanese Respiratory Society modified the definition of HCAP according to the
      medical environmental in Japan. We retrospectively observed HCAP patients and
      nursing home and healthcare-associated pneumonia (NHCAP) patients who were
      hospitalized during 24 months at the Japanese Red Cross Nagasaki Genbaku Hospital
      (Nagasaki, Japan). Patient background, disease severity, identified pathogens,
      initial antibiotic regimens, and outcomes were compared. A total of 108 patients
      (77 HCAP and 31 NHCAP except HCAP patients) were evaluated. Of NHCAP except HCAP
      patients, 27 (87.1 %) were above 3 in the ECOG PS score. There were almost no
      significant differences between the two groups in characteristics, pneumonia
      severity, identified bacteria, initial antibiotic regimens, and response rate of
      initial antibiotic therapy. Although the in-hospital mortality of HCAP patients
      and NHCAP except HCAP patients was 9.1 % and 19.4 %, respectively, this
      difference did not reach statistical significance (P > 0.05). Our study suggested
      that, in the criteria of HCAP, some Japanese patients, who were consistent with
      the concept of HCAP, were classified as community-acquired pneumonia (CAP).
      Therefore, there is a need to change the definition of HCAP according to the
      medical environment in Japan.

PMID- 22850822
TI  - Suppression of inherent ferromagnetism in Pr-doped CeO2 nanocrystals.
AB  - Ce(1-x)Pr(x)O(2-delta) (0 <= x <= 0.4) nanocrystals were synthesized by self
      propagating method and thoroughly characterized using X-ray diffraction, Raman
      and X-ray photoelectron spectroscopy and magnetic measurements. Undoped CeO2
      nanocrystals exhibited intrinsic ferromagnetism at room temperature. Despite the
      increased concentration of oxygen vacancies in doped samples, our results showed
      that ferromagnetic ordering rapidly degrades with Pr doping. The suppression of
      ferromagnetism can be explained in terms of the different dopant valence state,
      the different nature of the vacancies formed in Pr-doped samples and their
      ability/disability to establish the ferromagnetic ordering.

PMID- 22850823
TI  - Electronic transport and mechanical stability of carboxyl linked single-molecule
      junctions.
AB  - We characterize electron transport across Au-molecule-Au junctions of
      heterogeneous carboxyl and methyl sulfide terminated saturated and conjugated
      molecules. Low-bias conductance measurements are performed using the scanning
      tunneling microscopy based break-junction technique in the presence of solvents
      and at room temperature. For a series of alkanes with 1-4 carbon atoms in the
      hydrocarbon chain, our results show an exponential decrease in conductance with
      increasing molecule length characterized by a decay constant of 0.9 +/- 0.1 per
      methylene group. Control measurements in pH 11 solutions and with COOMe
      terminations suggest that the carboxylic acid group binds through the formation
      of a COO(-)-Au bond. Simultaneous measurements of conductance and force across
      these junctions yield a rupture force of 0.6 +/- 0.1 nN, comparable to that
      required to rupture a Au-SMe bond. By establishing reliable, in situ junction
      formation, these experiments provide a new approach to probe electronic
      properties of carboxyl groups at the single molecule level.

PMID- 22850819
TI  - Mitochondria as sensors and regulators of calcium signalling.
AB  - During the past two decades calcium (Ca(2+)) accumulation in energized
      mitochondria has emerged as a biological process of utmost physiological
      relevance. Mitochondrial Ca(2+) uptake was shown to control intracellular Ca(2+)
      signalling, cell metabolism, cell survival and other cell-type specific functions
      by buffering cytosolic Ca(2+) levels and regulating mitochondrial effectors.
      Recently, the identity of mitochondrial Ca(2+) transporters has been revealed,
      opening new perspectives for investigation and molecular intervention.

PMID- 22850824
TI  - Syringomyelia in preterm children with posthemorrhagic occlusive hydrocephalus.
AB  - OBJECTIVE AND IMPORTANCE: Whereas posthemorrhagic hydrocephalus is well known
      after preterm birth, its association with syringomyelia has been reported only
      once. Here, we describe two additional patients showing this rare constellation.
      CLINICAL PRESENTATION: The children had been born after 27 and 28 completed weeks
      of gestation, respectively. Both had developed neonatal cerebral hemorrhages. At
      the age of 4 years, patient 1 presented with progressive ataxia leading to the
      diagnosis of internal hydrocephalus and extensive syringomyelia. In patient 2,
      progressive ventriculomegaly and syringomyelia were diagnosed at the age of 4
      weeks. INTERVENTION: In both children, ventriculoperitoneal shunting resulted in
      clinical improvement, decrease of the ventricular size, and regression of the
      syringomyelia. After surgery, patient 1 developed a subdural hematoma and patient
      2 parenchymatous cerebral hemorrhages. CONCLUSION: The combination of
      syringomyelia and posthemorrhagic hydrocephalus may be more frequent than
      commonly assumed. Therefore, neurological deterioration may mandate spinal MRI in
      addition to cerebral MRI. Syringomyelia seems to result from impaired ventricular
      cerebrospinal fluid drainage as it regresses after ventriculoperitoneal shunting.
      Bleeding may complicate the postsurgical relaxation of distended brain
      parenchyma.

PMID- 22850825
TI  - Relationship between enzyme properties and disease progression in Canavan
      disease.
AB  - Canavan disease (CD) is a fatal neurological disorder caused by defects in the
      gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase
      catalyzes the deacetylation of N-acetylaspartate to produce acetate required for
      fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads
      to the demyelination and disrupted brain development that is found in CD
      patients. Sixteen different clinical mutants of aspartoacylase have been cloned,
      expressed and purified to examine their properties and the relationship between
      enzyme properties and disease phenotype. In contrast to numerous cell culture
      studies that reported virtually complete loss of function, each of these purified
      mutant enzymes was found to have measureable catalytic activity. However, the
      activities of these mutants are diminished, by as little as three-fold to greater
      than 100-fold when compared to the native enzyme. Many of these mutated enzyme
      forms show decreased thermal stability and an increased propensity for
      denaturation upon exposure to urea, but only four of the 16 mutants examined
      showed both diminished thermal and diminished conformational stability.
      Significantly, each of these lower stability mutants are responsible for the more
      severe phenotypes of CD, while patients with milder forms of CD have
      aspartoacylase mutants with generally high catalytic activity and with either
      good thermal or good conformational stability. These results suggest that the
      loss of catalytic function and the accumulation of N-acetylaspartate in Canavan
      disease is at least partially a consequence of the decreased protein stability
      caused by these mutations.

PMID- 22850826
TI  - Cascade dearomatization of N-substituted tryptophols via Lewis acid-catalyzed
      Michael reactions.
AB  - Lewis acid-catalyzed cascade dearomatization of N-substituted tryptophols via
      Michael addition reaction was developed. The generality of the method has been
      demonstrated by the synthesis of versatile furoindoline derivatives with a
      quaternary carbon center in good yields.

PMID- 22850827
TI  - Retraction note: Abstracts of the 2010 International MASCC/ISOO Symposium.

PMID- 22850828
TI  - Adherence to recommendation for chemotherapy-induced nausea and vomiting
      prophylaxis: the proposal of a score.

PMID- 22850829
TI  - Neurogenetics: Driving Abeta into reverse.

PMID- 22850831
TI  - Glia: Oligodendrocyte transporters feed axons.

PMID- 22850830
TI  - The many paths to fear.
AB  - Fear is an emotion that has powerful effects on behaviour and physiology across
      animal species. It is accepted that the amygdala has a central role in processing
      fear. However, it is less widely appreciated that distinct amygdala outputs and
      downstream circuits are involved in different types of fear. Data show that fear
      of painful stimuli, predators and aggressive members of the same species are
      processed in independent neural circuits that involve the amygdala and downstream
      hypothalamic and brainstem circuits. Here, we discuss data supporting multiple
      fear pathways and the implications of this distributed system for understanding
      and treating fear.

PMID- 22850833
TI  - Complex biomedical systems: from basic science to translation.
AB  - The Department of Biomedical Engineering (BME) of the University of Southern
      California (BME@USC) has a longstanding tradition of advancing biomedicine
      through the development and application of novel engineering ideas. More than 80
      primary and affiliated faculty members conduct cutting-edge research in a wide
      variety of areas, such as neuroengineering, biosystems and biosignal analysis,
      medical devices (including biomicroelectromechanical systems (bioMEMS) and
      bionanotechnology), biomechanics, bioimaging, and imaging informatics. Currently,
      the department hosts six internationally recognized research centers: the
      Biomimetic MicroElectronic Systems Engineering Research Center (funded by the
      National Science Foundation), the Biomedical Simulations Resource [funded by the
      National Institutes of Health (NIH)], the Medical Ultrasonic Transducer Center
      (funded by NIH), the Center for Neural Engineering, the Center for Vision Science
      and Technology (funded by an NIH Bioengineering Research Partnership Grant), and
      the Center for Genomic and Phenomic Studies in Autism (funded by NIH). BME@USC
      ranks in the top tier of all U.S. BME departments in terms of research funding
      per faculty.

PMID- 22850832
TI  - [Management of spinal metastases, strategies and surgical indications].
AB  - The number of bone metastases increases with prolonged survival of primary tumors
      of kidney, breast, prostate and other tumors. The spine is the most frequent site
      of bone metastases. This leads to high number of patients where the decision has
      to be made what kind of treatment should be the best. Several scores have been
      developed to solve this problem. The decision has to include the biology of the
      metastatic disease according to primary tumor and dissemination of the disease,
      the general condition of the patient, the residual stability of the spine, the
      neurologic status and most important the quality of life of the patient.
      Treatment options range from conservative treatment up to en bloc resection of
      the metastatic lesion. Therefore, the strategy of treatment always has to be
      decided on an individual base.

PMID- 22850834
TI  - Linking engineering and medicine: fostering collaboration skills in
      interdisciplinary teams.
AB  - Biomedical engineering embodies the spirit of combining disciplines. The
      engineer's pragmatic approach to--and appetite for--solving problems is matched
      by a bounty of technical challenges generated in medical domains. From nanoscale
      diagnostics to the redesign of systems of health-care delivery, engineers have
      been connecting advances in basic and applied science with applications that have
      helped to improve medical care and outcomes. Increasingly, however, integrating
      these areas of knowledge and application is less individualistic and more of a
      team sport. Success increasingly relies on a direct focus on practicing and
      developing collaboration skills in interdisciplinary teams. Such an approach does
      not fit easily into individual-focused, discipline-based programs. Biomedical
      engineering has done its fair share of silo busting, but new approaches are
      needed to inspire interdisciplinary teams to form around challenges in particular
      areas. Health care offers a wide variety of complex challenges across an array of
      delivery settings that can call for new interdisciplinary approaches. This was
      recognized by the deans of the University of Southern California's (USC's)
      Medical and Engineering Schools when they began the planning process, leading to
      the creation of the Health, Technology, and Engineering (HTE@USC or HTE for
      short) program. "Health care and technology are changing rapidly, and future
      physicians and engineers need intellectual tools to stay ahead of this change,"
      says Carmen A. Puliafito, dean of the Keck School of Medicine. His goal is to
      train national leaders in the quest for devices and processes to improve health
      care.

PMID- 22850835
TI  - Engineering excellence in breakthrough biomedical technologies: bioengineering at
      the University of California, Riverside.
AB  - The Department of Bioengineering at the University of California, Riverside
      (UCR), was established in 2006 and is the youngest department in the Bourns
      College of Engineering. It is an interdisciplinary research engine that builds
      strength from highly recognized experts in biochemistry, biophysics, biology, and
      engineering, focusing on common critical themes. The range of faculty research
      interests is notable for its diversity, from the basic cell biology through cell
      function to the physiology of the whole organism, each directed at breakthroughs
      in biomedical devices for measurement and therapy. The department forges future
      leaders in bioengineering, mirroring the field in being energetic,
      interdisciplinary, and fast moving at the frontiers of biomedical discoveries.
      Our educational programs combine a solid foundation in bio logical sciences and
      engineering, diverse communication skills, and training in the most advanced
      quantitative bioengineering research. Bioengineering at UCR also includes the
      Bioengineering Interdepartmental Graduate (BIG) program. With its slogan Start
      Grow-Be-BIG, it is already recognized for its many accomplishments, including
      being third in the nation in 2011 for bioengineering students receiving National
      Science Foundation graduate research fellowships as well as being one of the most
      ethnically inclusive programs in the nation.

PMID- 22850836
TI  - UCSD's Institute of Engineering in Medicine: fostering collaboration through
      research and education.
AB  - The University of California, San Diego (UCSD) was established in 1961 as a new
      research university that emphasizes innovation, excellence, and interdisciplinary
      research and education. It has a School of Medicine (SOM) and the Jacobs School
      of Engineering (JSOE) in close proximity, and both schools have national rankings
      among the top 15. In 1991, with the support of the Whitaker Foundation, the
      Whitaker Institute of Biomedical Engineering was formed to foster collaborations
      in research and education. In 2008, the university extended the collaboration
      further by establishing the Institute of Engineering in Medicine (IEM), with the
      mission of accelerating the discoveries of novel science and technology to
      enhance health care through teamwork between engineering and medicine, and
      facilitating the translation of innovative technologies for delivery to the
      public through clinical application and commercialization.

PMID- 22850837
TI  - Accelerating medical innovation at USC: realizing the dream of Alfred E. Mann.
AB  - Alfred E. Mann's vision is to create organizations that will help medical
      innovations born in academic environments evolve into commercially fit solutions,
      without the risk of being abandoned under the financial pressures early stage
      start-ups often experience. In 1998, Mann worked with Stephen Sample, president
      of USC, to create the first AMI for Biomedical Engineering, an organization
      fueled by an endowment valued at approximately US$160 million today. Technology
      acceleration centers come in different flavors. AMI USC's recipe has evolved
      since its creation, with edits that incorporate lessons learned and improvements
      brought by its expanding network of talented resource people. Its 15-member
      staff, consisting of three-fourths industry professionals, includes seasoned
      generalists and specialists in medical technology commercialization. Although the
      support varies with each invention, some recurring ingredients weave into the AMI
      approach to accelerating medical innovation.

PMID- 22850838
TI  - Evolution of bioengineering at UCSD: opening new vistas.
AB  - Before this, the field of bioengineering refers to biomedical engineering of
      prosthetic devices in physiology. In addition to exciting applications of
      engineering principles, UCSD Department of Bioengineering began to extend the
      notion of engineering models of physiological systems to physiological processes.
      This led to a conceptual shift in the discipline and contributed to the areas of
      tissue and physiological process engineering. In 1988, Dr. Shu Chien and Richard
      Skalak joined UCSD to begin research and education on cellular and molecular
      bioengineering, especially, mechanobiology. Dr. Fung and Dr. Skalak initiated the
      new field of tissue engineering. These two decades of evolution of bioengineering
      and its growth across the country was spearheaded by the Whitaker Foundation,
      whose leitmotif was the building of bioand biomedical engineering across the
      country. We have garnered other accomplishments in the following fields:
      regenerative medicine; bioinspired artificial extracellular matrices; flexible
      bioelectronics and tatoos; cells show how to synchronize biological clocks; and
      systems medicine.

PMID- 22850839
TI  - The next generation of exoskeletons: lighter, cheaper devices are in the works.
AB  - Many researchers and engineers are busy in their laboratories working on devices
      that will bring mobility to people who have lost function in the lower body due
      to an accident, stroke, multiple sclerosis, or other disorders. "Several pretty
      sophisticated exoskeletons are already on the market now, and they are all
      similar to each other in terms of technologies, but we're not ready to replace
      the wheelchair yet," said exoskeleton developer Homayoon Kaz Kazerooni, Ph.D.,
      professor of mechanical engineering at the University of California (UC) at
      Berkeley. "Eventually, we will have devices that are used by individuals on a
      daily basis to replace wheelchairs but not with the existing technology. We're at
      the beginning of a much bigger era in exoskeletons."

PMID- 22850840
TI  - KCo(H2O)2BP2O8.0.48H2O and K0.17Ca0.42Co(H2O)2BP2O8.H2O: two cobalt
      borophosphates with helical ribbons and disordered (K,Ca)/H2O schemes.
AB  - The two title compounds, potassium diaquacobalt(II) borodiphosphate 0.48-hydrate
      and potassium-calcium(0.172/0.418) diaquacobalt(II) borodiphosphate monohydrate,
      were synthesized hydrothermally. They are new members of the borophosphate family
      characterized by (infinity)[BP(2)O(8)](3-) helices running along [001] and
      constructed of boron (Wyckoff position 6b, twofold axis) and phosphorus
      tetrahedra. The [CoBP(2)O(8)](-) anionic frameworks in the two materials are
      structurally similar and result from a connection in the ab plane between the
      CoO(4)(H(2)O)(2) coordination octahedra (6b position) and the helical ribbons.
      Nevertheless, the two structures differ in the disorder schemes of the K,Ca and
      H(2)O species. The alkali cations in the structure of the pure potassium compound
      are disordered over three independent positions, one of them located on a 6b
      site. Its framework is characterized by double occupation of the tunnels by water
      molecules located on twofold rotation axes (6b) and a fraction of alkali cations;
      its cell parameters, compared with those for the mixed K,Ca compound, show
      abnormal changes, presumably due to the disorder. For the K,Ca compound, the K
      and Ca cations are on twofold axes (6b) and the channels are occupied only by
      disordered solvent water molecules. This shows that it is possible, due to the
      flexibility of the helices, to replace the alkali and alkaline earth cations
      while retaining the crystal framework.

PMID- 22850841
TI  - Crystal and electronic structures of La2LiGe6-x (x = 0.21) and La2LiGe4Si2.
AB  - The synthesis and characterization of a new ternary dilanthanum lithium
      hexagermanide, La(2)LiGe(6-x) (x = 0.21), belonging to the Pr(2)LiGe(6) structure
      type, and a quaternary dilanthanum lithium tetragermanium disilicide,
      La(2)LiGe(4)Si(2), which crystallizes as an ordered variant of this type, are
      reported. In both structures, Li is on a site of mmm symmetry. All other atoms
      are on sites of m2m symmetry. These structures are new representatives of a
      homologous linear structure series based on structural fragments of the AlB(2),
      CaF(2) and ZrSi(2) structure types. The observed 17-vertex polyhedra are typical
      for La atoms and the environment of the Li atom is cubic. Two Ge atoms are
      enclosed in a tetragonal prism with one added atom (nine-vertex polyhedron). The
      trigonal prismatic coordination is typical for Ge or Si atoms. The metallic
      nature of the bonding is indicated by the interatomic distances and electronic
      structure calculations.

PMID- 22850842
TI  - (Acetylacetonato-kappa2O,O')[1-(4-bromophenyl-kappaC2)-3-methylimidazol-2-ylidene
      kappaC2]platinum(II).
AB  - The title platinum(II) complex, [Pt(C(10)H(8)BrN(2))(C(5)H(7)O(2))], has a
      bidentate cyclometallated phenylimidazolylidene ligand and an acetylacetonate
      spectator ligand, which form a distorted square-planar coordination environment
      around the Pt(II) centre. In the solid state, the molecules are oriented in a
      parallel fashion by intermolecular hydrogen bonding and pi-pi and C-H...pi
      interactions, while close Pt...Pt contacts are not observed. The structure is
      only the second example for this new class of compounds.

PMID- 22850843
TI  - A new potential NLO compound with a supramolecular layered structure:
      aqua(hexamethylenetetramine-kappaN)(iminodiacetato-kappa3O,N,O')copper(II).
AB  - In the noncentrosymmetric title compound,
      [Cu(C(4)H(5)NO(4))(C(6)H(12)N(4))(H(2)O)] or [Cu(IDA)(HMTA)(H(2)O)], where IDA is
      iminodiacetate and HMTA is hexamethylenetetramine, the asymmetric unit consists
      of a whole mononuclear neutral molecule, where the Cu(II) cation is coordinated
      by two carboxylate O atoms and one N atom from the IDA ligand, by one N atom from
      the HMTA ligand and by the O atom of the coordinated water molecule, giving rise
      to a CuN(2)O(3) distorted square-pyramidal coordination geometry. The IDA and
      HTMA ligands adopt terminal tri- and monocoordinated modes, respectively. All
      adjacent molecules within the ac plane are connected to each other via two pairs
      of O-H...O and one N-H...O hydrogen bond, forming a (4,4) supramolecular two
      dimensional network. In the unit cell, these layers stack alternately in an
      ...ABABAB... sequence along the b axis. The optical absorption properties of this
      compound have been studied on powder samples, which had previously been examined
      by powder X-ray diffraction.

PMID- 22850844
TI  - A one-dimensional heterometallic coordination polymer with a three-dimensional
      supramolecular framework: poly[MU2-aqua-diaqua(2,2'-bipyridyl)(MU5-2
      sulfonatobutanedioato)copper(II)sodium(I)].
AB  - The title compound, [CuNa(C(4)H(3)O(7)S)(C(10)H(8)N(2))(H(2)O)(3)](n), consists
      of one Cu(II) cation, one Na(I) cation, one 2-sulfonatobutanedioate trianion
      (SSC(3-)), one 2,2'-bipyridyl (bpy) ligand and three coordinated water molecules
      as the building unit. The coordination of the Cu(II) cation is composed of two
      pyridyl N atoms, one water O atom and two carboxylate O atoms in a distorted
      square-pyramidal coordination geometry with an axial elongation. The Na(I) cation
      is six-coordinated by three water molecules and three carboxylate O atoms from
      three SSC(3-) ligands in a distorted octahedral geometry. Two SSC(3-) ligands
      link two Cu(II) cations to form a Cu(2)(SSC)(2)(bpy)(2) macrocyclic unit lying
      across an inversion centre, which is further linked by Na(I) cations via Na-O
      bonds to give a one-dimensional chain. Interchain hydrogen bonds link these
      chains to form a two-dimensional layer, which is further extended into a three
      dimensional supramolecular framework through pi-pi stacking interactions. The
      thermal stability of the title compound has also been investigated.

PMID- 22850845
TI  - Alkaline earth metal salts of 1-naphthoic acid.
AB  - The structures of the Mg, Ca, Sr and Ba salts of 1-naphthoic acid are examined
      and compared with analogous structures of salts of benzoate derivatives. It is
      shown that catena-poly[[[diaquabis(1-naphthoato-kappaO)magnesium(II)]-MU-aqua]
      dihydrate], {[Mg(C(11)H(7)O(2))(2)(H(2)O)(3)].2H(2)O}(n), exists as a one
      dimensional coordination polymer that propagates only through Mg-OH(2)-Mg
      interactions along the crystallographic b direction. In contrast with related
      benzoate salts, the naphthalene systems are large enough to prevent inorganic
      chain-to-chain interactions, and thus species with inorganic channels rather than
      layers are formed. The Ca, Sr and Ba salts all have metal centres that lie on a
      twofold axis (Z' = 1/2) and all have the common name catena
      poly[[diaquametal(II)]-bis(MU-1-naphthoato)-kappa(3)O,O':O;kappa(3)O:O,O'],
      [M(C(11)H(7)O(2))(2)(H(2)O)(2)](n), where M = Ca, Sr or Ba. The Ca and Sr salts
      are essentially isostructural, and all three species form one-dimensional
      coordination polymers through a carboxylate group that forms three M-O bonds. The
      polymeric chains propagate via c-glide planes and through MOMO four-membered
      rings. Again, inorganic channel structures are formed rather than layered
      structures, and the three structures are similar to those found for Ca and Sr
      salicylates and other substituted benzoates.

PMID- 22850846
TI  - Poly[[(MU2-4,4'-bipyridine)(MU3-5-isonicotinamidoisophthalato)cobalt(II)]
      trihydrate].
AB  - In the title compound, {[Co(C(14)H(8)N(2)O(5))(C(10)H(8)N(2))].3H(2)O}(n), the
      Co(II) cation is five-coordinated with a slightly distorted trigonal-bipyramidal
      geometry, and the 5-isonicotinamidoisophthalate ligands link Co(II) atoms into a
      layered structure. These two-dimensional arrays are further pillared by rod-like
      4,4'-bipyridine ligands to give a three-dimensional framework with pcu (primitive
      cubic) topology. The magnetic and adsorption properties of the title compound are
      also discussed.

PMID- 22850847
TI  - Pseudosymmetry in a cyclopalladated compound.
AB  - The enantiomerically pure title complex, [SP-4-4]-(R)-[2-(1-aminoethyl)phenyl
      kappa(2)C(1),N]chlorido(quinoline-kappaN)palladium(II) acetone hemisolvate,
      [Pd(C(8)H(10)N)Cl(C(9)H(7)N)].0.5C(3)H(6)O, crystallizes with four molecules of
      the organopalladium complex and two molecules of acetone in the asymmetric unit.
      This corresponds to a discrete hydrogen-bonded aggregate and to the content of
      the unit cell in the space group P1. Pronounced pseudo-inversion symmetry relates
      pairs of these objects in the asymmetric unit.

PMID- 22850848
TI  - Tris[3,6-di-tert-butyl-1-(isoquinolin-1-yl)naphthalen-2-olato
      kappa2N,O]aluminium(III) toluene sesquisolvate.
AB  - The central Al(III) atom of the title compound,
      [Al(C(27)H(28)NO)(3)].1.5C(7)H(8), has octahedral geometry in which the three N
      atoms are arranged in a meridional fashion. One of the toluene solvent molecules
      is located on a general position, while the second is disordered around a centre
      of inversion. The ligand molecule has axial chirality, and two of the three
      ligands in the complex exhibit the same stereochemistry. The three independent
      chelate rings exhibit significantly different bite angles at the metal atom, with
      one [83.72 (8) degrees ] notably smaller than the other two [87.22 (8) and 87.13
      (8) degrees ]. Calculation of the solid angle covered by the ligands at the metal
      atom reveals that coverage is greatest for the ligand group with the shortest Al
      O bond distance.

PMID- 22850849
TI  - A novel one-dimensional silver cylinder stabilized by mixed 2-mercaptobenzoic
      acid and ethylenediamine ligands.
AB  - A novel infinite one-dimensional silver cylinder, namely poly[MU-ethylenediamine
      MU(5)-(2-sulfanidylbenzoato)-MU(4)-(2-sulfanidylbenzoato)-tetrasilver(I)],
      [Ag(4)(C(7)H(4)O(2)S)(2)(C(2)H(8)N(2))](n), has been synthesized by one-pot
      reaction of equivalent molar silver nitrate and 2-mercaptobenzoic acid (H(2)mba)
      in the presence of ethylenediamine (eda). One Ag atom is located in an AgS(2)NO
      four-coordinated tetrahedral geometry, two other Ag atoms are in an AgS(2)O three
      coordinated T-shaped geometry and the fourth Ag atom is in an AgSNO coordination
      environment. The two mba ligands show two different binding modes. The MU(2)-N:N'
      eda ligand, acting as a bridge, combines with mba ligands to extend the Ag(I)
      ions into a one-dimensional silver cylinder incorporating abundant Ag...Ag
      interactions ranging from 2.9298 (11) to 3.2165 (13) A. Interchain N-H...O
      hydrogen bonds extend the one-dimensional cylinder into an undulating two
      dimensional sheet, which is further packed into a three-dimensional
      supramolecular framework by van der Waals interactions; no pi-pi interactions
      were observed in the crystal structure.

PMID- 22850850
TI  - The first dinuclear cobalt complex bridged by acetylamidate ligands: di-MU
      acetylamido-kappa2O:N;kappa2N:O-di-MU-hydroxido-kappa4O:O-bis[bis(pyridine
      kappaN)cobalt(III)] bis(perchlorate) acetonitrile disolvate.
AB  - The title compound,
      [Co(2)(C(2)H(4)NO)(2)(OH)(2)(C(5)H(5)N)(4)](ClO(4))(2).2C(2)H(3)N, consists of
      two octahedral Co(III) centers arranged around an inversion point in which two
      cis hydroxide and two trans acetylamidate ligands link the two centers together,
      forming a dimeric cationic complex. Each Co(III) center has two cis pyridine
      ligands which coordinate in the same plane as the cis hydroxide ligands. Two
      acetonitrile solvent molecules and two perchlorate anions are hydrogen bonded to
      the H atoms on the bridging hydroxide and acetylamidate (N atom) ligands,
      respectively.

PMID- 22850851
TI  - Two (E)-2-({[4-(dialkylamino)phenyl]imino}methyl)-4-nitrophenols.
AB  - The slow evaporation of analytical NMR samples resulted in the formation of
      crystals of (E)-2-({[4-(dimethylamino)phenyl]imino}methyl)-4-nitrophenol,
      C(15)H(15)N(3)O(3), (I), and (E)-2-({[4-(diethylamino)phenyl]imino}methyl)-4
      nitrophenol, C(17)H(19)N(3)O(3), (II). Despite the small structural difference
      between these two N-salicylideneaniline derivatives, they show different space
      groups and diverse molecular packing. The molecules of both compounds are close
      to being planar due to an intramolecular O-H...N hydrogen bond. The 4-alkylamino
      substituted benzene ring is inclined at an angle of 13.44 (19) degrees  in (I)
      and 2.57 (8) degrees  in (II) with respect to the 4-nitro-substituted phenol
      ring. Only very weak intermolecular pi-pi stacking and C-H...O interactions were
      found in these structures.

PMID- 22850852
TI  - The effect of partial methylation of the glycine amino group on crystal structure
      in N,N-dimethylglycine and its hemihydrate.
AB  - N,N-Dimethylglycine, C(4)H(9)NO(2), and its hemihydrate, C(4)H(9)NO(2).0.5H(2)O,
      are discussed in order to follow the effect of the methylation of the glycine
      amino group (and thus its ability to form several hydrogen bonds) on crystal
      structure, in particular on the possibility of the formation of hydrogen-bonded
      'head-to-tail' chains, which are typical for the crystal structures of amino
      acids and essential for considering amino acid crystals as mimics of peptide
      chains. Both compounds crystallize in centrosymmetric space groups (Pbca and
      C2/c, respectively) and have two N,N-dimethylglycine zwitterions in the
      asymmetric unit. In the anhydrous compound, there are no head-to-tail chains but
      the zwitterions form R(4)(4)(20) ring motifs, which are not bonded to each other
      by any hydrogen bonds. In contrast, in the crystal structure of N,N
      dimethylglycinium hemihydrate, the zwitterions are linked to each other by N
      H...O hydrogen bonds into infinite C(2)(2)(10) head-to-tail chains, while the
      water molecules outside the chains provide additional hydrogen bonds to the
      carboxylate groups.

PMID- 22850853
TI  - Supramolecular networks in (9-fluoro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol and
      its 9-chloro analogue at 100 K.
AB  - The title compounds, (9-fluoro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol,
      C(11)H(8)FNO(3), (I), and (9-chloro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol,
      C(11)H(8)ClNO(3), (II), crystallize in the orthorhombic space group Pbca with Z'
      = 1 and the triclinic space group P-1 with Z' = 6, respectively. The simple
      replacement of F by Cl in the main molecular scaffold of (I) and (II) results in
      significant differences in the intermolecular interaction patterns and a
      corresponding change in the point-group symmetry from D(2h) to C(i) = S(2). These
      striking differences are manifested through the presence of C-H...F and the
      absence of O-H...O and C-H...O interactions in (I), and the absence of C-H...Cl
      and the presence of O-H...O and C-H...O interactions in (II). However, the
      geometry of the synthons formed by the O-H...N and O-H...X (X = F or Cl)
      interactions observed in the constitution of the supramolecular networks of both
      (I) and (II) remains similar. Also, C-H...O interactions are not preferred in the
      presence of F in (I), while they are much preferred in the presence of Cl in
      (II).

PMID- 22850854
TI  - (+/-)-2,2-Dimethyl-5-oxotetrahydrofuran-3-carboxylic acid (terebic acid): a
      racemic layered structure.
AB  - A racemic crystalline form of terebic acid, C(7)H(10)O(4), which is an important
      industrial chemical compound, is reported for the first time. The crystal
      structure is stabilized by O-H...O and C-H...O hydrogen bonds which form racemic
      double layers parallel to (001).

PMID- 22850855
TI  - Enantiomerically pure (1S,5R) and racemic 3-(1-benzothiophen-2-yl)-8
      azoniabicyclo[3.2.1]oct-2-ene acetate.
AB  - The title compound, C(15)H(16)NS(+).C(2)H(3)O(2)(-), has been crystallized as
      both a pure enantiomer (1S,5R) and a racemate. The racemate crystallizes in the
      space group Cc, with molecules of opposite handedness related to each other by
      the action of the c-glide. The enantiomer is essentially isostructural with the
      racemate, except that the glide symmetry is violated by interchange of CH and
      CH(2) groups within the seven-membered ring. The space-group symmetry is reduced
      to P1 with two molecules in the asymmetric unit. The enantiomer structure shows
      disorder of the thiophene ring for one of the molecules in the asymmetric unit.
      The major component of the disorder has the thiophene ring in the same position
      as in the racemate, but generates a higher-energy molecular conformation. The
      minor disorder component has different intermolecular interactions but retains a
      more stable molecular conformation.

PMID- 22850856
TI  - Structures of benzoxazine-fused triazoles as potential diuretic agents.
AB  - 6,8-Dinitro-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one,
      C(9)H(5)N(5)O(6), (I), a potential diuretic, and its acetylacetone derivative (E)
      2-(2-hydroxy-4-oxopent-2-en-3-yl)-6,8-dinitro-2,4-dihydro-1H
      benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one, C(14)H(11)N(5)O(8), (II), both
      crystallize from methanol but in centrosymmetric and noncentrosymmetric space
      groups, respectively. To the best of our knowledge, this is the first report of
      crystal structures of benzoxazine-triazole fused systems. The acetylacetone group
      in (II) exists as the keto-enol tautomer and is oriented perpendicular to the
      triazol-3-one ring. Of the two nitro groups present, one is rotated significantly
      less than the other in both structures. The oxazine ring adopts a screw-boat
      conformation in (II), whereas it is almost planar in (I). N-H...N and N-H...O
      hydrogen bonds form centrosymmetric dimers in (I), while C-H...O interactions
      associate the molecules into helical columns in (II).

PMID- 22850857
TI  - (1-{[2-(6-Methoxynaphthalen-1-yl)ethyl]amino}ethylidene)oxidanium bromide
      monohydrate.
AB  - The title salt, C(15)H(18)NO(2)(+).Br(-).H(2)O, is an analogue of the
      antidepressant drug agomelatine. The cation is protonated at the carbonyl O atom
      of its amide group. The side chain at the 1-position adopts an extended
      conformation, with all non-H atoms lying in the same plane as the naphthalene
      ring. This is in contrast with the crystal structures known for three agomelatine
      polymorphs, and also with two known cocrystals containing agomelatine. The
      structure displays three types of hydrogen bond, namely C=O-H...O, N-H...Br and O
      H...Br, which define a two-dimensional network parallel to the (100) plane. The
      naphthalene rings interdigitate in a 'zipper-like' fashion between these hydrogen
      bonded networks, forming an offset arrangement. Direct face-to-face pi-pi
      contacts between naphthalene rings are not present in the structure.

PMID- 22850858
TI  - The first 3':5'-cyclic nucleotide-amino acid complex: L-His-cIMP.
AB  - In the crystal structure of the L-His-cIMP complex, i.e. L-histidinium inosine
      3':5'-cyclic phosphate [systematic name: 5-(2-amino-2-carboxyethyl)-1H-imidazol-3
      ium 7-hydroxy-2-oxo-6-(6-oxo-6,9-dihydro-1H-purin-9-yl)-4a,6,7,7a-tetrahydro-4H
      1,3,5,2lambda(5)-furo[3,2-d][1,3,2lambda(5)]dioxaphosphinin-2-olate],
      C(6)H(10)N(3)O(2)(+).C(10)H(10)N(4)O(7)P(-), the Hoogsteen edge of the
      hypoxanthine (Hyp) base of cIMP and the Hyp face are engaged in specific amino
      acid-nucleotide (His...cIMP) recognition, i.e. by abutting edge-to-edge and by pi
      pi stacking, respectively. The Watson-Crick edge of Hyp and the cIMP phosphate
      group play a role in nonspecific His...cIMP contacts. The interactions between
      the cIMP anions (anti/C3'-endo/trans-gauche/chair conformers) are realized mainly
      between riboses and phosphate groups. The results for this L-His-cIMP complex,
      compared with those for the previously reported solvated L-His-IMP crystal
      structure, indicate a different nature of amino acid-nucleotide recognition and
      interactions upon the 3':5'-cyclization of the nucleotide phosphate group.

PMID- 22850859
TI  - A new polymorph of physcion.
AB  - The structure of the title compound, 7-methoxy-2-methyl-4,5-dihydroxyanthracene
      9,10-dione, C(16)H(12)O(5), was originally reported by Ulicky et al. [Acta Cryst.
      (1991). C47, 1879-1881] in the space group P2(1)2(1)2(1) [polymorph (Io)]. The
      new polymorph, (Im), crystallizes in the space group P2(1)/c. The molecular
      structures are closely similar, with both -OH groups forming intramolecular
      hydrogen bonds to one of the neighbouring quinone O atoms, thus slightly
      lengthening this C=O bond; the pattern of C-C bond lengths in the ring system is
      consistent with some contribution from a resonance form with a negative charge at
      the hydrogen-bonded quinone O atom and an aromatic region around its neighbouring
      C atoms. The packing of (Im) is simpler than the extensively crosslinked pattern
      of (Io), with molecular tapes connected by classical (but three-centre) and
      'weak' hydrogen bonds, parallel to [201].

PMID- 22850860
TI  - Cinerin C: a macrophyllin-type bicyclo[3.2.1]octane neolignan from Pleurothyrium
      cinereum (Lauraceae).
AB  - The structure of naturally-occurring cinerin C [systematic name:
      (7S,8R,3'R,4'S,5'R)-Delta(8')-4'-hydroxy-5,5',3'-trimethoxy-3,4-methylenedioxy
      2',3',4',5'-tetrahydro-2'-oxo-7.3',8.5'-neolignan], isolated from the ethanol
      extract of leaves of Pleurothyrium cinereum (Lauraceae), has previously been
      established by NMR and HRMS spectroscopy, and its absolute configuration
      established by circular dichroism measurements. For the first time, its crystal
      structure has now been established by single-crystal X-ray analysis, as the
      monohydrate, C(22)H(26)O(7).H(2)O. The bicyclooctane moiety comprises fused
      cyclopentane and cyclohexenone rings which are almost coplanar. An intermolecular
      O-H...O hydrogen bond links the 4'-OH and 5'-OCH(3) groups along the c axis.

PMID- 22850861
TI  - (1S)-1-Phenylethanaminium 4-{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H-[2,2'-biinden]
      2-yl]methyl}benzoate.
AB  - The title molecular salt, C(8)H(12)N(+).C(26)H(21)O(3)(-), contains a dimeric
      indane pharmacophore that demonstrates potent anti-inflammatory activity. The
      indane group of the anion exhibits some disorder about the alpha-C atom, which
      appears common to many structures containing this group. A model to account for
      the slight disorder was attempted, but this was deemed unsuccessful because
      applying bond-length constraints to all the bonds about the alpha-C atom led to
      instability in the refinement. The absolute configuration was determined
      crystallographically as S,S,S by anomalous dispersion methods with reference to
      both the Flack parameter and Bayesian statistics on Bijvoet differences. The
      configuration was also determined by an a priori knowledge of the absolute
      configuration of the (1S)-1-phenylethanaminium counter-ion. The molecules pack in
      the crystal structure to form an infinite two-dimensional hydrogen-bond network
      in the (100) plane of the unit cell.

PMID- 22850862
TI  - Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta
      analysis.
AB  - INTRODUCTION: To more precisely estimate the association between the tumor
      necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and
      systemic lupus erythematosus (SLE) risk, we surveyed studies on the association
      of the TNFSF4 rs2205960, rs1234315, rs844644, and rs844648 polymorphisms with
      SLE. METHODS: A literature-based search was conducted to identify all relevant
      studies. A total of eight independent studies were identified and subsequently
      reviewed in the meta-analysis. RESULTS: The meta-analysis showed an association
      between the TNFSF4 rs2205960 polymorphism and SLE in all subjects [ odds ratio
      (OR) 1.327, 95% confidence interval (CI) 1.227-1.436, P < 0.001]. In a subgroup
      analysis by ethnicity, a significantly increased risk for SLE was associated with
      TNFSF4 rs2205960 T allele among patients of European (OR 1.254, 95% CI 1.185
      1.328, P < 0.001) and Asian ethnicity (OR 1.425, 95% CI 1.352-1.501, P < 0.001).
      The meta-analysis of the rs1234315 polymorphism revealed no association between
      SLE and the rs1234315 T allele in all subjects (OR 1.167, 95% CI 0.874-1.558, P =
      0.296), but the results of the subgroup analysis revealed significant association
      in subjects of Asian ethnicity (OR 1.386, 95% CI 1.318-1.458, P < 0.001). No
      association was found between the rs844644 and rs844648 polymorphisms and SLE.
      CONCLUSION: The results of our meta-analysis suggest that the TNFSF4 rs2205960
      polymorphism may confer susceptibility to SLE in different populations and that
      the TNFSF4 rs1234315 polymorphism is associated with susceptibility to SLE in
      Asians.

PMID- 22850863
TI  - Influence of chemical functionalization on the CO2/N2 separation performance of
      porous graphene membranes.
AB  - The separation of CO2 from a mixture of CO2 and N2 using a porous graphene
      membrane was investigated using molecular dynamics (MD) simulations. The effects
      of chemical functionalization of the graphene sheet and pore rim on the gas
      separation performance of porous graphene membranes were examined. It was found
      that chemical functionalization of the graphene sheet can increase the absorption
      ability of CO2, while chemical functionalization of the pore rim can
      significantly improve the selectivity of CO2 over N2. The results show that the
      porous graphene membrane with all-N modified pore-16 exhibits a higher CO2
      selectivity over N2 (~11) due to the enhanced electrostatic interactions compared
      to the unmodified graphene membrane. This demonstrates the potential use of
      functionalized porous graphene as single-atom-thick membrane for CO2 and N2
      separation. We provide an effective way to improve the gas separation performance
      of porous graphene membranes, which may be useful for designing new concept
      membranes for other gases.

PMID- 22850866
TI  - Sarcopenia prevalence.

PMID- 22850867
TI  - Sarcopenia prevalence: reply to comment by Perez-Zepeda et al.

PMID- 22850865
TI  - Solution, surface, and single molecule platforms for the study of DNA-mediated
      charge transport.
AB  - The structural core of DNA, a continuous stack of aromatic heterocycles, the base
      pairs, which extends down the helical axis, gives rise to the fascinating
      electronic properties of this molecule that is so critical for life. Our
      laboratory and others have developed diverse experimental platforms to
      investigate the capacity of DNA to conduct charge, termed DNA-mediated charge
      transport (DNA CT). Here, we present an overview of DNA CT experiments in
      solution, on surfaces, and with single molecules that collectively provide a
      broad and consistent perspective on the essential characteristics of this
      chemistry. DNA CT can proceed over long molecular distances but is remarkably
      sensitive to perturbations in base pair stacking. We discuss how this foundation,
      built with data from diverse platforms, can be used both to inform a mechanistic
      description of DNA CT and to inspire the next platforms for its study: living
      organisms and molecular electronics.

PMID- 22850868
TI  - Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1
      producing cells.
AB  - BACKGROUND: Metformin is the most frequently prescribed drug for treatment of
      type 2 diabetes. It improves insulin resistance and glycemia by reducing hepatic
      gluconeogenesis. In addition, diabetic patients on metformin therapy have
      elevated levels of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and
      metformin has been shown to regulate the expression of the GLP-1R in the
      pancreas. METHODS: We have studied the direct long-term effects of metformin on
      apoptosis, and function of GLP-1-secreting L cells in vitro, using the murine
      GLUTag cell line as a model. The apoptosis of GLUTag cells was detected by DNA
      fragment assay and caspase-3 activity determination. GLP-1 secretion was
      determined using ELISA and the expression of proglucagon mRNA was assessed by
      reverse transcription polymerase chain reaction. The activation of intracellular
      messengers was determined using western blotting. RESULTS: Metformin
      significantly decreased lipotoxicity-induced apoptosis in conjunction with
      increased phosphorylated AMPK. Metformin also countered the JNK2 activation
      evoked by lipotoxicity. In addition, long-term metformin treatment stimulated GLP
      1 secretion. CONCLUSION: This study demonstrates that metformin protects against
      lipoapoptosis (possibly by blocking JNK2 activation), and enhances GLP-1
      secretion from GLP-1-producing cells in vitro. These direct effects of the drug
      might explain the elevated plasma GLP-1 levels seen in diabetic patients on
      chronic metformin therapy. The findings may also be harnessed to therapeutic
      advantage in efforts aiming at enhancing endogenous GLP-1 secretion in type 2
      diabetic patients.

PMID- 22850869
TI  - Entecavir and interferon-alpha sequential therapy in Japanese patients with
      hepatitis B e antigen-positive chronic hepatitis B.
AB  - BACKGROUND: The outcomes of sequential therapy with lamivudine followed by
      interferon have been unsatisfactory in Japanese patients with hepatitis B
      envelope antigen (HBeAg)-positive chronic hepatitis B. However, the efficacy of
      sequential therapy with entecavir and interferon remains unclear. METHODS: Twenty
      four HBeAg-positive patients (23 men and 1 woman; mean age 39 +/- 7 years)
      received entecavir 0.5 mg alone for 36-52 weeks, followed by entecavir plus
      interferon-alpha for 4 weeks, and lastly by interferon-alpha alone for 20 weeks.
      Twenty-three patients had genotype C infection, and one had genotype A infection.
      RESULTS: No entecavir-resistant mutant variants emerged in any patient. Hepatitis
      flare occurred in three patients during interferon-alpha treatment after the
      withdrawal of entecavir, but none had hepatic decompensation. Serum hepatitis B
      surface antigen levels did not change during or after therapy. Serum hepatitis B
      core-related antigen levels were significantly decreased at the start (P <
      0.0001) and at the end of interferon-alpha treatment (P < 0.0001), but returned
      to baseline levels after treatment. Twenty-four weeks after the completion of the
      sequential therapy, a sustained biochemical, virological, and serological
      response was achieved in 5 (21 %) patients. The proportion of patients in whom
      HBeAg was lost during entecavir treatment was significantly higher among those
      with a sustained response than among those with no response (P = 0.015).
      CONCLUSIONS: The rate of response to sequential therapy with entecavir and
      interferon-alpha in Japanese patients with HBeAg-positive chronic hepatitis B was
      not higher than the rate in previous studies of lamivudine followed by
      interferon.

PMID- 22850870
TI  - Microembolization and myonecrosis during elective percutaneous coronary
      interventions in diabetic patients: an intracoronary Doppler ultrasound study
      with 2-year clinical follow-up.
AB  - Elevation of cardiac troponin I (cTnI) is a well-known complication after
      percutaneous coronary interventions (PCI). The aims of this study were to
      quantify the extent of coronary microembolization during elective PCI, to
      identify predisposing anatomical and procedural factors, and to evaluate its
      impact on long-term outcome in diabetic patients with a high cardiovascular risk.
      48 patients (pts, median 66.7 years) with type 2 diabetes and coronary artery
      disease underwent elective PCI with stenting to treat single-vessel lesions. Real
      time microembolization during PCI ("HITS") was detected by an intracoronary
      Doppler guide wire. Peak levels of cTnI were measured within 24 h after PCI. Pts
      were followed for 2 years to record major cardiac events (MACE: death, myocardial
      infarction, revascularization of target and non-target vessels). In 47 patients
      microemboli were detected during PCI. Nineteen patients showed pathologic cTnI
      elevation (0.13-28.9, median 0.39 MUg/l). The amount of HITS correlated with cTnI
      levels (r = 0.43, p = 0.003), but not with other clinical or angiographic data.
      Within 2 years MACE were detected in 9 patients, who had significantly more
      microemboli (15.4 +/- 11.8 vs. 28.2 +/- 16.0 HITS; p = 0.009, OR 1.07; 95 % CI
      1.011-1.13) during PCI. HITS >23, but not cTnI elevation, predicted later MACE
      (ROC analysis, p = 0.025). A high amount of microembolization during elective PCI
      in diabetic patients appears to be an indicator of greater atherosclerotic burden
      and accelerated coronary artery disease progression, associated with acute
      biomarker elevation and adverse long-term outcomes.

PMID- 22850871
TI  - Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic
      mitochondrial pathway.
AB  - Rhein is a primary anthraquinone found in the roots of a traditional Chinese
      herb, rhubarb, and has been shown to have some anticancer effects. The aim of the
      present study was to investigate the effect of rhein on the apoptosis of the
      human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC
      7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 uM) for
      24, 48, or 72 h. Relative cell viability assessed by the MTT assay after
      treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and
      100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with
      TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining
      at 48 h after 100, 200 and 300 um rhein. The percentage of apoptotic cells was
      7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and
      -9 using real-time PCR. Treatment with 100 uM rhein for 48 h significantly
      increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related
      proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein
      treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein
      levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the
      expression of cytochrome c and apoptotic protease activating factor 1, two
      critical components involved in mitochondrial pathway-mediated apoptosis. We
      conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and
      this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial
      pathway.

PMID- 22850872
TI  - Antimicrobial peptides and nitric oxide production by neutrophils from
      periodontitis subjects.
AB  - Neutrophils play an important role in periodontitis by producing nitric oxide
      (NO) and antimicrobial peptides, molecules with microbicidal activity via oxygen
      dependent and -independent mechanisms, respectively. It is unknown whether
      variation in the production of antimicrobial peptides such as LL-37, human
      neutrophil peptides (HNP) 1-3, and NO by neutrophils influences the pathogenesis
      of periodontal diseases. We compared the production of these peptides and NO by
      lipopolysaccharide (LPS)-stimulated neutrophils isolated from healthy subjects
      and from patients with periodontitis. Peripheral blood neutrophils were cultured
      with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS), Porphyromonas
      gingivalis-LPS (Pg-LPS) and Escherichia coli-LPS (Ec-LPS). qRT-PCR was used to
      determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3
      and LL-37 proteins in the cell culture supernatants were also determined by
      ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated
      by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa
      LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from
      healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients
      stimulated with Aa-LPS. Neutrophils from periodontitis patients produced
      significantly higher LL-37 protein levels than neutrophils from healthy subjects
      when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3
      production. Neutrophils from periodontitis patients cultured or not with Pg-LPS
      and Ec-LPS produced significantly lower NO levels than neutrophils from healthy
      subjects. The significant differences in the production of LL-37 and NO between
      neutrophils from healthy and periodontitis subjects indicate that production of
      these molecules might influence individual susceptibility to important
      periodontal pathogens.

PMID- 22850873
TI  - Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic
      related, defensive responses in rats tested in the elevated T-maze.
AB  - The escape response to electrical or chemical stimulation of the dorsal
      periaqueductal gray matter (DPAG) has been associated with panic attacks. In
      order to explore the validity of the DPAG stimulation model for the study of
      panic disorder, we determined if the aversive consequences of the electrical or
      chemical stimulation of this midbrain area can be detected subsequently in the
      elevated T-maze. This animal model, derived from the elevated plus-maze, permits
      the measurement in the same rat of a generalized anxiety- and a panic-related
      defensive response, i.e., inhibitory avoidance and escape, respectively.
      Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was
      detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min
      after DPAG electrical stimulation (current generated by a sine-wave stimulator,
      frequency at 60 Hz) or after local microinjection of the GABA A receptor
      antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h
      before testing) or chemical stimulation of this midbrain area did not affect
      escape performance in the elevated T-maze or locomotion in an open-field. No
      change in the two behavioral tasks measured by the elevated T-maze was observed
      after repetitive (3 trials) electrical stimulation of the DPAG. The results
      indicate that activation of the DPAG caused a short-lived, but selective,
      increase in defensive behaviors associated with generalized anxiety.

PMID- 22850874
TI  - A tasty cultural event.

PMID- 22850875
TI  - Crystalline glucosamine sulfate in the management of knee osteoarthritis:
      efficacy, safety, and pharmacokinetic properties.
AB  - Glucosamine is an amino monosaccharide and a natural constituent of
      glycosaminoglycans in articular cartilage. When administered exogenously, it is
      used for the treatment of osteoarthritis as a prescription drug or a dietary
      supplement. The latter use is mainly supported by its perception as a cartilage
      building block, but it actually exerts specific pharmacologic effects, mainly
      decreasing interleukin 1-induced gene expression by inhibiting the cytokine
      intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB)
      activation in particular. As a whole, the use of glucosamine in the management of
      osteoarthritis is supported by the clinical trials performed with the original
      prescription product, that is, crystalline glucosamine sulfate. This is the
      stabilized form of glucosamine sulfate, while other formulations or different
      glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In
      particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg
      once daily have shown significant and clinically relevant improvement of pain and
      function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous
      administration for up to 3 years resulted in significant reduction in the
      progression of joint structure changes compared with placebo as assessed by
      measuring radiologic joint space narrowing (structure-modifying effect). The two
      effects combined may suggest a disease-modifying effect that was postulated based
      on an observed decrease in the risk of undergoing total joint replacement in the
      follow up of patients receiving the product for at least 12 months in the pivotal
      trials. The safety of the drug was good in clinical trials and in the
      postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is
      therefore recommended in the majority of clinical practice guidelines and was
      found to be cost effective in pharmacoeconomic analyses. Compared with other
      glucosamine formulations, salts, or dosage forms, the prescription product
      achieves higher plasma and synovial fluid concentrations that are above the
      threshold for a pharmacologically relevant effect, and may therefore justify its
      distinct therapeutic characteristics.

PMID- 22850876
TI  - Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV
      infections.
AB  - Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by
      increased susceptibility to specific human papillomaviruses, the
      betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin
      carcinomas in otherwise healthy individuals. Inactivating mutations in
      epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most,
      but not all, patients with autosomal recessive EV. We found that 2 young adult
      siblings presenting with T cell deficiency and various infectious diseases,
      including persistent EV-HPV infections, were homozygous for a mutation creating a
      stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an
      atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients'
      circulating T cells contained predominantly effector memory T cells, which
      displayed impaired TCR signaling. Additionally, very few circulating T cells
      expressed the beta7 integrin subunit, which homes T cells to specific tissues.
      Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally
      small numbers of circulating beta7-positive cells. Expression of the WT, but not
      of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T
      cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH
      deficiency leads to T cell defects and persistent EV-HPV infections, suggesting
      that T cells play a role in the pathogenesis of chronic EV-HPV infections.

PMID- 22850877
TI  - ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a
      expression.
AB  - Metastatic cancer is extremely difficult to treat, and the presence of metastases
      greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1
      transcriptional repressor promotes metastasis through downregulation of microRNAs
      (miRs) that are strong inducers of epithelial differentiation and inhibitors of
      stem cell factors. Given that each miR can target multiple genes with diverse
      functions, we posited that the prometastatic network controlled by ZEB1 extends
      beyond these processes. We tested this hypothesis using a mouse model of human
      lung adenocarcinoma metastasis driven by ZEB1, human lung carcinoma cells, and
      human breast carcinoma cells. Transcriptional profiling studies revealed that
      ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs,
      including miR-34a. Ectopic expression of miR-34a decreased tumor cell invasion
      and metastasis, inhibited the formation of promigratory cytoskeletal structures,
      suppressed activation of the RHO GTPase family, and regulated a gene expression
      signature enriched in cytoskeletal functions and predictive of outcome in human
      lung adenocarcinomas. We identified several miR-34a target genes, including
      Arhgap1, which encodes a RHO GTPase activating protein that was required for
      tumor cell invasion. These findings demonstrate that ZEB1 drives prometastatic
      actin cytoskeletal remodeling by downregulating miR-34a expression and provide a
      compelling rationale to develop miR-34a as a therapeutic agent in lung cancer
      patients.

PMID- 22850878
TI  - A botulinum toxin-derived targeted secretion inhibitor downregulates the GH/IGF1
      axis.
AB  - Botulinum neurotoxins (BoNTs) are zinc endopeptidases that block release of the
      neurotransmitter acetylcholine in neuromuscular synapses through cleavage of
      soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein receptor
      (SNARE) proteins, which promote fusion of synaptic vesicles to the plasma
      membrane. We designed and tested a BoNT-derived targeted secretion inhibitor
      (TSI) targeting pituitary somatotroph cells to suppress growth hormone (GH)
      secretion and treat acromegaly. This recombinant protein, called SXN101742,
      contains a modified GH-releasing hormone (GHRH) domain and the endopeptidase
      domain of botulinum toxin serotype D (GHRH-LHN/D, where HN/D indicates
      endopeptidase and translocation domain type D). In vitro, SXN101742 targeted the
      GHRH receptor and depleted a SNARE protein involved in GH exocytosis, vesicle
      associated membrane protein 2 (VAMP2). In vivo, administering SXN101742 to
      growing rats produced a dose-dependent inhibition of GH synthesis, storage, and
      secretion. Consequently, hepatic IGF1 production and resultant circulating IGF1
      levels were reduced. Accordingly, body weight, body length, organ weight, and
      bone mass acquisition were all decreased, reflecting the biological impact of
      SXN101742 on the GH/IGF1 axis. An inactivating 2-amino acid substitution within
      the zinc coordination site of the endopeptidase domain completely abolished
      SXN101742 inhibitory actions on GH and IGF1. Thus, genetically reengineered BoNTs
      can be targeted to nonneural cells to selectively inhibit hormone secretion,
      representing a new approach to treating hormonal excess.

PMID- 22850879
TI  - Targets of antibodies against Plasmodium falciparum-infected erythrocytes in
      malaria immunity.
AB  - Plasmodium falciparum is the major cause of malaria globally and is transmitted
      by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes
      (P. falciparum-IEs) express multiple polymorphic proteins known as variant
      surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein
      1 (PfEMP1). VSA-specific antibodies are associated with protection from
      symptomatic and severe malaria. However, the importance of the different VSA
      targets of immunity to malaria remains unclear, which has impeded an
      understanding of malaria immunity and vaccine development. In this study, we
      developed assays using transgenic P. falciparum with modified PfEMP1 expression
      to quantify serum antibodies to VSAs among individuals exposed to malaria. We
      found that the majority of the human antibody response to the IE targets PfEMP1.
      Furthermore, our longitudinal studies showed that individuals with PfEMP1
      specific antibodies had a significantly reduced risk of developing symptomatic
      malaria, whereas antibodies to other surface antigens were not associated with
      protective immunity. Using assays that measure antibody-mediated phagocytosis of
      IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the
      major target of these functional antibodies. Taken together, these data
      demonstrate that PfEMP1 is a key target of humoral immunity. These findings
      advance our understanding of the targets and mediators of human immunity to
      malaria and have major implications for malaria vaccine development.

PMID- 22850881
TI  - Take a deep breath: pulmonary research inspires.
AB  - The lung is a complex organ with multiple functions; in addition to facilitating
      gas exchange, it also serves as the first line of defense against inhaled
      environmental pathogens and toxins. Given these critical roles, disruption of
      normal cell function or cell-cell interactions can have devastating health
      consequences. The articles of this Review Series highlight recent progress in
      understanding the pathophysiology of several pulmonary diseases and suggest how
      these insights are leading to the development of new therapeutic strategies.

PMID- 22850880
TI  - Alarmins: awaiting a clinical response.
AB  - Alarmins are endogenous molecules that are constitutively available and released
      upon tissue damage and activate the immune system. Current evidence indicates
      that uncontrolled and excessive release of alarmins contributes to the
      dysregulated processes seen in many inflammatory and autoimmune conditions, as
      well as tumorigenesis and cancer spread. Conversely, alarmins have also been
      found to play a major role in the orchestration of tissue homeostasis, including
      repair and remodeling in the heart, skin, and nervous system. Here, we provide an
      update and overview on alarmins, highlighting the areas that may benefit from
      this clinical translation.

PMID- 22850882
TI  - Building and maintaining the epithelium of the lung.
AB  - Airspaces of the lung are lined by an epithelium whose cellular composition
      changes along the proximal-to-distal axis to meet local functional needs for
      mucociliary clearance, hydration, host defense, and gas exchange. Advances in
      cell isolation, in vitro culture techniques, and genetic manipulation of animal
      models have increased our understanding of the development and maintenance of the
      pulmonary epithelium. This review discusses basic cellular mechanisms that
      regulate establishment of the conducting airway and gas exchange systems as well
      as the functional maintenance of the epithelium during postnatal life.

PMID- 22850883
TI  - The acute respiratory distress syndrome.
AB  - The acute respiratory distress syndrome (ARDS) is an important cause of acute
      respiratory failure that is often associated with multiple organ failure. Several
      clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration
      of gastric contents, and major trauma. Physiologically, ARDS is characterized by
      increased permeability pulmonary edema, severe arterial hypoxemia, and impaired
      carbon dioxide excretion. Based on both experimental and clinical studies,
      progress has been made in understanding the mechanisms responsible for the
      pathogenesis and the resolution of lung injury, including the contribution of
      environmental and genetic factors. Improved survival has been achieved with the
      use of lung-protective ventilation. Future progress will depend on developing
      novel therapeutics that can facilitate and enhance lung repair.

PMID- 22850884
TI  - Asthma as a chronic disease of the innate and adaptive immune systems responding
      to viruses and allergens.
AB  - Research on the pathogenesis of asthma has traditionally concentrated on
      environmental stimuli, genetic susceptibilities, adaptive immune responses, and
      end-organ alterations (particularly in airway mucous cells and smooth muscle) as
      critical steps leading to disease. The focus of this cascade has been the
      response to allergic stimuli. An alternative scheme suggests that respiratory
      viruses and the consequent response of the innate immune system also drives the
      development of asthma as well as related inflammatory diseases. This conceptual
      shift raises the possibility that sentinel cells such as airway epithelial cells,
      DCs, NKT cells, innate lymphoid cells, and macrophages also represent critical
      components of asthma pathogenesis as well as new targets for therapeutic
      discovery. A particular challenge will be to understand and balance the innate as
      well as the adaptive immune responses to defend the host against acute infection
      as well as chronic inflammatory disease.

PMID- 22850885
TI  - Pathogenesis of chronic obstructive pulmonary disease.
AB  - The current epidemic of chronic obstructive pulmonary disease (COPD) has produced
      a worldwide health care burden, approaching that imposed by transmittable
      infectious diseases. COPD is a multidimensional disease, with varied intermediate
      and clinical phenotypes. This Review discusses the pathogenesis of COPD, with
      particular focus on emphysema, based on the concept that pulmonary injury
      involves stages of initiation (by exposure to cigarette smoke, pollutants, and
      infectious agents), progression, and consolidation. Tissue damage entails complex
      interactions among oxidative stress, inflammation, extracellular matrix
      proteolysis, and apoptotic and autophagic cell death. Lung damage by cigarette
      smoke ultimately leads to self-propagating processes, resulting in macromolecular
      and structural alterations - features similar to those seen in aging.

PMID- 22850887
TI  - Prevalence and risk factors of the female sexual dysfunction in a sample of
      infertile Iranian women.
AB  - BACKGROUND: Infertility has a major impact on women's quality of life and
      emotional well-being. The resulting interpersonal problems extend to women's
      sexual relationships, with a high proportion of infertile women reporting sexual
      problems. AIM: To determine the prevalence and identify the potential risk
      factors of female sexual dysfunction (FSD) among infertile Iranian women.
      METHODS: Using a cross-sectional study design including 12 infertility clinics in
      five Iranian cities, FSD was assessed in 604 infertile women using the culturally
      adapted, multidimensional Female Sexual Function Index (IV-FSFI). Depression,
      anxiety and health-related quality of life (HRQL) were also assessed for all
      infertile patients. Depression and anxiety were assessed with the Hospital
      Anxiety and Depression Scale (HADS) while HRQL was measured using the Short Form
      36 (SF-36). MAIN OUTCOME MEASURE: Prevalence of FSD in infertile women and
      associated factors. RESULTS: Infertile women reported significantly lower scores
      on the FSFI domains in comparison with healthy women. Risk factors for FSD as
      determined by multilevel analyses were older age and self-reported depression.
      Furthermore, secondary infertility, lower educational level and higher partner
      education put women at increased risk for FSD. CONCLUSIONS: Among infertile
      women, sexual dysfunctions seem to be prevalent higher than previously published
      in Iran. This finding may have implications on the clinical assessment of sexual
      function and the role of demographic and psychological factors in infertile
      women.

PMID- 22850886
TI  - Pulmonary fibrosis: patterns and perpetrators.
AB  - Pulmonary fibrosis occurs in a variety of clinical settings, constitutes a major
      cause of morbidity and mortality, and represents an enormous unmet medical need.
      However, the disease is heterogeneous, and the failure to accurately discern
      between forms of fibrosing lung diseases leads to inaccurate treatments.
      Pulmonary fibrosis occurring in the context of connective tissue diseases is
      often characterized by a distinct pattern of tissue pathology and may be amenable
      to immunosuppressive therapies. In contrast, idiopathic pulmonary fibrosis (IPF)
      is a progressive and lethal form of fibrosing lung disease that is recalcitrant
      to therapies that target the immune system. Although animal models of fibrosis
      imperfectly recapitulate IPF, they have yielded numerous targets for therapeutic
      intervention. Understanding the heterogeneity of these diseases and elucidating
      the final common pathways of fibrogenesis are critical for the development of
      efficacious therapies for severe fibrosing lung diseases.

PMID- 22850888
TI  - Successful management of mucinous ovarian cancer by conservative surgery in week
      6 of pregnancy: case report and literature review.
AB  - PURPOSE: The management of ovarian cancer during pregnancy is still a big
      challenge, mostly due to the reciprocal impacts between cancer and pregnancy. The
      objective of this article is to present a rare case of maternal ovarian
      adenocarcinoma and review published similar cases about this clinical condition.
      MATERIALS AND METHODS: Here we report a rare case of maternal ovarian
      adenocarcinoma detected during gestational week 6, with good pregnancy outcome
      treated with conservative surgery. RESULTS AND DISCUSSION: A case of maternal
      ovarian adenocarcinoma (stage I) was detected in week 6 of pregnancy receiving
      conservative surgery without chemotherapy. In week 39 of pregnancy, due to
      relapse of the cancer, the patient underwent excision of the isolated tumor, and
      gave birth to a healthy baby through cesarian section. After that, the patient
      received cytoreductive surgery associated with six chemotherapy. The patient was
      finally diagnosed as epithelial ovarian cancer stage IIIC, and had survived more
      than 5 years without relapse. The successful experience from this case suggested
      that pregnancy complicated with early ovarian cancer receiving conservative
      surgery could continue to pregnancy and the effect of cesarian section followed
      with cytoreductive surgery associated with six chemotherapy at full term was
      still satisfied.

PMID- 22850889
TI  - The effect of vacuum operator's experience on Apgar scores.
AB  - OBJECTIVE: To determine the effect of a vacuum operator's experience on Apgar
      scores. METHODS: A historical cohort study was conducted. All women who delivered
      by vacuum extraction between January 2003 and December 2007 at Songklanagarind
      Hospital were recruited. Vacuum operators were divided into two groups: staff
      doctors and residents. Comparisons of Apgar scores and rates of low Apgar scores
      (<=7) between the two groups were studied. A multivariate logistic regression
      analysis was used to control confounding variables for low Apgar scores. RESULTS:
      The percentages for the procedure performed by the staff doctors and residents
      were 76.9 and 23.1%. At 1 min, the rates of low Apgar scores in the staff and
      resident groups were 6.7 and 24.1% (p<0.001), and at 5 min, the rates of low
      Apgar scores were 0.6 and 5.2% (p<0.001). Multivariate logistic regression
      analysis showed that the operator's experience was an independent risk factor for
      low Apgar scores. The residents had a 2.9-fold increased risk of low Apgar scores
      at 1 min compared with the staff doctors (adjusted odds ratio 2.9; 95% confidence
      interval 1.7-6.8). In the resident group, the third year residents had the lowest
      risk of low Apgar scores. CONCLUSIONS: The vacuum operator's experience was an
      independent risk factor for low Apgar scores. Improvement of the residency
      training program is mandatory.

PMID- 22850890
TI  - Postpartum cervical prolapses preceded by precipitated labour.

PMID- 22850891
TI  - Chiral-Sc catalyzed asymmetric Michael addition/protonation of thiols with enones
      in water.
AB  - Asymmetric Michael reactions and enantioselective protonations between enones and
      thiols were catalyzed by a Sc(OTf)(3)-chiral 2,2'-bipyridine complex in water.
      The remarkable governing of the enantioselectivity for simple introduction of
      protons despite their abnormally high mobility in water may provide us with new
      synthetic opportunities as well as significant chemical advances.

PMID- 22850894
TI  - MRI in residual tumor size measurement in patient with breast cancer receiving
      neoadjuvant chemotherapy calls for caution.

PMID- 22850893
TI  - Transcriptional activation of breast cancer-associated gene 2 by estrogen
      receptor.
AB  - RNF115, or Breast Cancer-Associated Gene 2 (BCA2), encodes a RING-finger
      ubiquitin E3 ligase, expression of which was associated with estrogen receptor
      (ER)-positive status in human breast tumors. Although the BCA2 promoter contains
      several estrogen response element (ERE) half-sites, the role of ER in the
      regulation of BCA2 transcription has not been reported. The aim of this study is
      to investigate the molecular mechanism by which estrogen regulates BCA2
      transcription. BCA2 mRNA and protein levels were examined by RT-PCR and Western
      blot analysis, respectively, and localization was assessed by immunofluorescence.
      BCA2 promoter activity in response to E(2) was tested by a dual luciferase
      reporter assay and ER binding to the BCA2 promoter was examined by chromatin
      immunoprecipitation assay. We found that BCA2 mRNA and protein levels are
      regulated by estrogen in ER-positive MCF7 breast cancer cells and MDA MB 231
      cells stably transfected with ER. Estrogen treatment in hormonal depleted MCF7
      and MDA MB 231/ER stably transfected cells resulted in increased nuclear ER and
      cytoplasmic and nuclear BCA2 staining. Cycloheximide is not able to inhibit BCA2
      mRNA levels, suggesting potential BCA2 regulation at the transcriptional level.
      Anti-estrogens like tamoxifen and ICI 182 178 counteracted E(2)-induced BCA2
      protein and knockdown of ER by ER siRNA resulted in a significant decrease in
      BCA2 protein and a lower nuclear expression pattern. Estrogen treatment lead to a
      significant increase in BCA2 promoter response, associated with increased binding
      of ER to the ERE region of the BCA2 promoter. BCA2 is therefore a newly
      identified transcriptional target of estrogen receptor.

PMID- 22850895
TI  - Development of a five-plex flow cytometric immunoassay for the simultaneous
      detection of six coccidiostats in feed and eggs.
AB  - Coccidiostats are the only veterinary drugs still permitted to be used as feed
      additives to treat poultry for coccidiosis. To protect consumers, maximum levels
      for their presence in food and feed have been set by the European Union (EU). To
      monitor these coccidiostats, a rapid and inexpensive screening method would be a
      useful tool. The development of such a screening method, using a flow cytometry
      based immunoassay, is described. The assay uses five sets of colour-coded
      paramagnetic microspheres for the detection of six selected priority
      coccidiostats. Different coccidiostats, with and without carrier proteins, were
      covalently coupled onto different bead sets and tested in combination with
      polyclonal antisera and with a fluorescent-labelled secondary antibody. The five
      optimal combinations were selected for this multiplex and a simple-to-use sample
      extraction method was applied for screening blank and spiked eggs and feed
      samples. A very good correlation (r ranging from 0.995 to 0.999) was obtained
      with the responses obtained in two different flow cytometers (Luminex 100 and
      FLEXMAP 3D). The sensitivities obtained were in accordance with the levels set by
      the EU as the measured limits of detection for narasin/salinomycin, lasalocid,
      diclazuril, nicarbazin (4,4'-dinitrocarbanilide) and monensin in eggs were 0.01,
      0.1, 0.5, 53 and 0.1 MUg/kg and in feed 0.1, 0.2, 0.3, 9 and 1.5 MUg/kg,
      respectively.

PMID- 22850896
TI  - Parts per trillion level determination of endocrine-disrupting chlorinated
      compounds in river water and wastewater effluent by stir-bar-sorptive extraction
      followed by gas chromatography-triple quadrupole mass spectrometry.
AB  - A new analytical method using stir-bar-sorptive extraction (SBSE) followed by
      liquid desorption (LD) and gas chromatography with triple-quadrupole mass
      spectrometric detection (GC-QqQ-MS-MS) has been used for quantitative
      determination of 25 chlorinated endocrine-disrupting compounds (EDCs) in river
      water and wastewater. The experimental conditions affecting the SBSE-LD
      performance were studied and are discussed in detail. Results from systematic
      assay revealed that a 100-mL water sample, stir bars coated with 47 MUL PDMS, an
      extraction time of 14 h (at 900 rpm), 5 % MeOH as modifier and 10 % NaCl resulted
      in the best analytical recovery of all the target compounds studied. Use of 1:1
      ACN-MeOH as back-extraction solvent and two successive sonication steps, each for
      5 min, resulted in the best performance for monitoring EDCs in water matrices.
      The method detection limits for most of the target compounds were very good- <= 2
      ng L(-1) and <=10 ng L(-1) for river water and wastewater effluents respectively.
      Experimental recovery for all the compounds was >70 %, with the exception of
      simazine for which recovery from the matrix was 65 %. Signal enhancement observed
      for a few of the compounds in wastewater effluents was managed by use of matrix
      matched standards and different injection liners. The method was successfully
      used for analysis of river water samples from Henares River (Spain) and
      wastewater effluent samples from wastewater-treatment plants (WWTP). Eleven of
      the 25 compounds studied were detected in both river water and wastewater
      effluents. Terbutylazine and methoxychlor were detected in almost all the river
      water and effluent samples; amounts varied between 37-58.5 ng L(-1) and 15.2-46.8
      ng L(-1), respectively. This method was shown enable reliable, effective, and
      sensitive monitoring of chlorinated EDCs at nanogram levels in surface water and
      wastewater effluent.

PMID- 22850897
TI  - Characterization of perchlorate in a new frozen human urine standard reference
      material.
AB  - Perchlorate, an inorganic anion, has recently been recognized as an environmental
      contaminant by the US Environmental Protection Agency. Urine is the preferred
      matrix for assessment of human exposure to perchlorate. Although the measurement
      technique for perchlorate in urine was developed in 2005, the calibration and
      quality assurance aspects of the metrology infrastructure for perchlorate are
      still lacking in that there is no certified reference material (CRM) traceable to
      the International System of Units. To meet the quality assurance needs in
      biomonitoring measurements of perchlorate and the related anions that affect
      thyroid health, the National Institute of Standards and Technology (NIST), in
      collaboration with the Centers for Disease Control and Prevention (CDC),
      developed Standard Reference Material (SRM) 3668 Mercury, Perchlorate, and Iodide
      in Frozen Human Urine. SRM 3668 consists of perchlorate, nitrate, thiocyanate,
      iodine, and mercury in urine at two levels that represent the 50th and 95th
      percentiles, respectively, of the concentrations (with some adjustments) in the
      US population. It is the first CRM being certified for perchlorate. Measurements
      leading to the certification of perchlorate were made collaboratively at NIST and
      CDC using three methods based on liquid or ion chromatography tandem mass
      spectrometry. Potential sources of bias were analyzed, and results were compared
      for the three methods. Perchlorate in SRM 3668 Level I urine was certified to be
      2.70 +/- 0.21 MUg L(-1), and for SRM 3668 Level II urine, the certified value is
      13.47 +/- 0.96 MUg L(-1).

PMID- 22850899
TI  - Aerobic oxidation of beta-isophorone catalyzed by N-hydroxyphthalimide: the key
      features and mechanism elucidated.
AB  - Due to the insufficient understanding of the selective oxidation mechanism of
      alpha/beta-isophorones (alpha/beta-IP) to ketoisophorone (KIP), the key features
      in the beta-IP oxidation catalyzed by N-hydroxyphthalimide (NHPI) have been
      explored via theoretical calculations. beta-IP is more favourable to being
      activated by phthalimide-N-oxyl radical (PINO) and peroxyl radical (ROO) than
      alpha-IP owing to the different C-H strengths at their reactive sites, thereby
      exhibiting selective product distributions. It was found that NHPI accelerates
      beta-IP activation due to the higher reactivity of PINO than ROO and the
      equilibrium reaction between them, yielding considerable hydroperoxide (ROOH) and
      ROO. In addition, the ROOH decomposition is more favourable viaalpha-H
      abstraction by radicals than its self-dehydration and thermal dissociation. The
      strong exothermicity of this alpha-H abstraction, along with that from H
      abstraction by co-yielded hot HO, is in favor of the straightforward formation of
      KIP, simultaneously leading to the isomerization of a few beta-IP to alpha-IP and
      production of 4-hydroxyisophorone (HIP) and water. The proposed mechanisms,
      consistent with the experimental observations, allow for the deeper understanding
      and effective design of oxidation systems involving similar substrates or NHPI
      analogues that are of industrial importance.

PMID- 22850898
TI  - Basis of a FTIR spectroscopy methodology for automated evaluation of Akt kinase
      inhibitor on leukemic cell lines used as model.
AB  - The PI3K/Akt-signaling pathway, associated with cancer development and disease
      progression, is recognized to be an anti-tumor drug target that could present
      important therapeutic benefit. However, no targeted Akt medicines have been
      commercialized yet, reflecting that drug selection procedures requires
      significant improvement from early research to clinical trials. Thus, new methods
      permitting both the evaluation of cytotoxic and proliferation inhibition effect
      on cancer cells but also to provide a global fingerprint of the drug action
      mechanism of new Akt inhibitor candidates are of major interest. Because it can
      detect very subtle molecular changes and could provide a global fingerprint of
      drug effects on cells, Fourier-transform infrared (FTIR) spectroscopy appears to
      be a promising method to develop new time- and cost-saving tools for chemical
      library screening improvements. In this study, we combine FTIR spectroscopy,
      advanced chemometrics analysis and cross-validation by standard biological assays
      to establish a basis of a mid-throughput methodology for rapid and automated
      assessment of cell response to Akt inhibitors and quantitative evaluation of
      their anti-proliferative effects. Our results shows that our methodology is able
      (1) to detect cell response to an Akt inhibitor exposure even for very low doses,
      (2) to provide biochemical information of interest about its effects on the cell
      metabolism, lipidome, and proteome, (3) to predict accurately resulting cell
      proliferation inhibition rate. Thus, further based on a large spectral data base,
      our methodology could contribute to facilitate preliminary screening of chemical
      libraries and improving the selection procedure of drug candidates in laboratory
      routine.

PMID- 22850900
TI  - Smoke-free environments: age, sex, and educational disparity in 25 Argentinean
      cities.
AB  - BACKGROUND: There is scarce evidence of secondhand smoke (SHS) and disparity in
      developing countries. We evaluated the relationship between socio-demographic
      variables and secondhand smoke-related factors in Argentina. METHODS: We
      conducted a randomized telephone survey (2008/2009) in 25 Argentinean cities. We
      included a sample of 160 respondents per city stratified by sex and age. We used
      different generalized multivariate regression models with a confidence interval
      of 95 % for the five outcome variables. RESULTS: We sampled 4,000 respondents,
      52.2 % women, 36 % adolescents and young adults (15-29 years), 58 % >=12 years of
      education, and 72.6 % nonsmokers. Support to 100 % smoke-free environment
      legislation was higher in older than in younger respondents, OR = 1.5 (IC: 1.2
      2.0), and in people with higher education levels, OR = 1.2 (IC: 1.1-1.4).
      Exposure to SHS was significantly lower in men than in women at home and in
      public places, IRR = 0.7 (IC: 0.5-0.9) and IRR  = 0.8 (IC: 0.6-0.9),
      respectively. Older respondents reported lower exposure at home and in public
      places than adolescents and young adults, IRR = 0.6 (IC: 0.4-0.8) and IRR = 0.4
      (IC: 0.3-0.5), respectively. People with higher education levels had a higher
      level of exposure in indoor public places than less educated people, IRR = 1.1
      (IC: 1.1-1.2). Knowledge of respiratory disease in children caused by SHS
      exposure was lower in men than in women, RRR = 0.3 (IC: 0.1-0.6). Perceived
      compliance was higher in men than in women, OR = 1.4 (IC: 1.1-1.8) and in people
      with higher education levels, OR = 1.2 (IC: 1.1-1.4). Older and more educated
      respondents were more empowered than. younger and less educated people, OR = 1.5
      (IC: 1.2-1.9) and OR = 1.2 (IC: 1.1-1.3), respectively. Reference groups for each
      variable were age: 15-29; education: <=7 years; and sex: men. CONCLUSIONS: This
      is the first study to explore socio-demographic variables regarding secondhand
      smoke in our country. Women and younger people are more vulnerable to SHS-related
      factors in Argentina.

PMID- 22850901
TI  - Estimating prevalence of distant metastatic breast cancer: a means of filling a
      data gap.
AB  - PURPOSE: To develop and validate a method for estimating numbers of people with
      distant cancer metastases, for evidence-based service planning. METHODS:
      Estimates were made employing an illness-death model with distant metastatic
      cancer as the illness state- and site-specific mortality as an outcome, using
      MIAMOD software. To demonstrate the method, we estimated numbers of females alive
      in Australia following detection of distant metastatic breast cancer during 1980
      2004, using data on patient survival from an Australian population-based cancer
      registry. We validated these estimates by comparing them with direct prevalence
      counts. RESULTS: Relative survival at 10 years following detection of distant
      metastases was low (5-20 %), with better survival experienced by: (1) females
      where distant metastatic disease was detected at initial diagnosis rather than
      subsequently (e.g., at recurrence); (2) those diagnosed in more recent calendar
      years; and (3) younger age groups. For Australian females aged less than 85
      years, the modeled cumulative risk of detection of distant metastatic breast
      cancer (either at initial diagnosis or subsequently) declined over time, but
      numbers of cases with this history rose from 71 per 100,000 in 1980 to 84 per
      100,000 in 2004. The model indicated that there were approximately 3-4 prevalent
      distant metastatic breast cancer cases for every breast cancer death. Comparison
      of estimates with direct prevalence counts showed a reasonable level of
      agreement. CONCLUSIONS: The method is straightforward to apply and we recommend
      its use for breast and other cancers when registry data are insufficient for
      direct prevalence counts. This will provide estimates of numbers of people who
      would need ongoing medical surveillance and care following detection of distant
      metastases.

PMID- 22850902
TI  - Efficacy, safety and mechanism of action of modified-release prednisone in
      rheumatoid arthritis.
AB  - Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and
      disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about
      adverse effects are driving efforts to find 'safer' GC or GC analogues. One novel
      approach has been to change the timing of GC delivery, targeting the early hours
      of the morning to suppress the observed circadian peak in interleukin-6 (IL-6).
      The CAPRA-1 study has shown that this produces a clinically useful beneficial
      improvement in morning stiffness and mechanistic studies have shown that this
      correlates with a strong suppression of the IL-6 early morning peak. With no
      obvious additional adverse reactions, this improvement in the therapeutic ratio
      offers additional treatment options in RA, and perhaps in other inflammatory
      diseases that show circadian variation in symptoms.

PMID- 22850903
TI  - Does a digital regional nerve block improve the accuracy of noninvasive
      hemoglobin monitoring?
AB  - BACKGROUND: Blood hemoglobin (Hb) can be continuously monitored utilizing
      noninvasive spectrophotometric finger sensors (Masimo SpHb). SpHb is not a
      consistently accurate guide to transfusion decisions when compared with
      laboratory Co-Oximetry (tHb). We evaluated whether a finger digital nerve block
      (DNB) would increase perfusion and, thereby, improve the accuracy of SpHb.
      METHODS: Twenty adult patients undergoing spinal surgery received a DNB with
      lidocaine to the finger used for the monitoring of SpHb. SpHb-tHb differences
      were determined immediately following the DNB and approximately every hour
      thereafter. These differences were compared with those in our previously reported
      patients (N = 20) with no DNB. The SpHb-tHb difference was defined as "very
      accurate" if <0.5 g/dL and "inaccurate" if >2.0 g/dL. Perfusion index (PI) values
      at the time of each SpHb-tHb measurement were compared. RESULTS: There were 57
      and 78 data points in this and our previous study, respectively. The presence of
      a DNB resulted in 37 % of measurements having SpHb values in the "very accurate
      group" versus 12 % in patients without a DNB. When the PI value was >2.0, only 1
      of 57 DNB values was in the "inaccurate" group. The PI values were both higher
      and less variable in the patients who received a DNB. CONCLUSIONS: A DNB
      significantly increased the number of "very accurate" SpHb values and decreased
      the number of "inaccurate" values. We conclude that a DNB may facilitate the use
      of SpHb as a guide to transfusion decisions, particularly when the PI is >2.0.

PMID- 22850905
TI  - Pericardial cytokines in neoplastic, autoreactive, and viral pericarditis.
AB  - Pericardial cytokine patterns in various diseases are not well established. We
      have analyzed pericardial proinflammatory (interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha) and immunoregulatory cytokines (transforming growth factor
      (TGF)-beta1 and interferon (IFN)-gamma) in patients with pericarditis,
      myocarditis, and ischemic heart disease. Pericardial fluid was obtained in 30
      subsequent patients undergoing pericardiocentesis (Group 1: 60 % males, 52.4 +/-
      14.2 years) and in 21 patients during aortocoronary bypass surgery (Group 2: 42.9
      % males, age 67.2 +/- 7.4 years). After clinical, laboratory, echocardiography
      examination, fiberoptic pericardioscopy (Storz-AF1101Bl, Germany) and
      pericardial/epicardial biopsy Group 1 was subdivided to 40 % neoplastic, 36.6 %
      autoreactive, 10 % iatrogenic, and 13.3 % viral pericarditis. Samples were
      promptly aliquoted, frozen, and stored at -70  degrees C. The cytokines were
      estimated using quantikine enzyme amplified-sensitivity immuno-assays (R&D
      Systems, USA) and the results compared between neoplastic, viral, iatrogenic, and
      autoreactive pericarditis and surgical groups. IL-6 was significantly increased
      in PE versus serum in all forms of pericarditis (except in autoreactive) and
      increased in comparison with pericardial fluid of surgical patients. TNF-alpha
      was increased only in PE of patients with viral pericarditis in comparison with
      Group 2. TGF-beta1 was strikingly lower in the PE than in the serum of all
      pericarditis patients. However, TGF-beta1 levels in PE were significantly higher
      in Group 1 than in Group 2, except in viral pericarditis. IFN-gamma levels did
      not significantly differ between PE and serum or in comparison with Group 2. The
      cytokine pattern "high TNF-alpha/low TGF-beta1" was found in viral pericarditis
      and low IL-6 in autoreactive PE. Different etiologies of pericardial inflammation
      did not influence the IFN-gamma levels. IL-6 pericardial to serum ratio was
      significantly higher in autoreactive PE than in viral and neoplastic forms.
      However, TNF-alpha and IFN-gamma pericardial to serum ratios were significantly
      higher in viral than in autoreactive and neoplastic PE.

PMID- 22850906
TI  - Genetic factors regulating inflammation and DNA methylation associated with
      prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCa) displays a strong familiarity component and
      genetic factors; genes regulating inflammation may have a pivotal role in the
      disease. Epigenetic changes control chromosomal integrity, gene functions and
      ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT)
      contributes to S-adenosylmethionine level regulation and, by affecting DNA
      methylation, influences gene expression. The genotype and allele distribution of
      single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular
      endothelial growth factor (VEGF), interleukin (IL)-10, IL-1beta, alpha-1
      antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and
      the influence of GNMT SNP upon DNA methylation in a PCa case-control study have
      been investigated. METHODS: SNPs of VEGF (rs699947), ACT (rs1884082), IL-1beta
      (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or
      by real-time PCR methods. DNA methylation was assessed by an ELISA assay.
      RESULTS: Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T
      allele were higher in PCa. The concomitant presence of the AA genotype of VEGF,
      the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA
      methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest
      level of DNA methylation. CONCLUSIONS: SNPs in VEGF, IL-10 and GNMT genes might
      have a synergistic role in the development of PCa. The GNMT T allele may
      influence PCa risk by affecting DNA methylation and prostate gene expression. Our
      observations might help implement the screening of unaffected subjects with an
      increased susceptibility to develop PCa.

PMID- 22850907
TI  - Sphenoid sinus fungus ball.
AB  - The objective of this retrospective study is to present a large series of
      patients with sphenoid sinus fungus ball (SSFB) and describe clinical
      manifestations, diagnostic workup, surgical treatment, and eventual complications
      of this disease. We included patients operated on for this disease over a 14-year
      period. All patients benefited from mid-to-long-term follow-up. There were 28
      patients (18 females, 10 males, mean age 64 years). Main symptoms were posterior
      rhinorrhea and headache. Less common symptoms were alteration of vision or ocular
      mobility and cacosmia. Preoperative diagnosis was based on nasal endoscopy and CT
      scanning. MRI was performed in case of suspicion of a tumor, an intraorbital or
      intracranial invasion. Treatment consisted in endoscopic transnasal or
      transethmoidal sphenoidotomy with removal of the fungus ball. Specimens were sent
      to pathology and mycology to confirm diagnosis. Postoperative complications
      consisted of two cases of epistaxis and two other cases of bacterial
      superinfection of the operated sphenoid cavity. No recurrence of the fungus ball
      was seen after a mean follow-up of 13 months. To conclude, SSFB is a relatively
      uncommon entity, usually due to Aspergillus infection. Although not invasive, if
      left untreated, it can lead to long-term serious complications. Preoperative
      nasal endoscopic examination and CT scan are the standard tools for diagnosis.
      Endoscopic sphenoidotomy with removal of the fungus ball is the current treatment
      because it has proven effective and has a low morbidity and recurrence rate.

PMID- 22850909
TI  - Enantioselective synthesis of 8-epi-xanthatin and biological evaluation of
      xanthanolides and their derivatives.
AB  - An enantioselective synthesis of 8-epi-xanthatin (9) has been accomplished
      starting from the bicyclic lactone 3, which has been used for the synthesis of
      other xanthanolides, sundiversifolide (4) and diversifolide (5), through a
      synthetic route without the use of a selenium species. Additionally we have
      evaluated antimicrobial activities of five natural xanthanolides and their
      derivatives. Although the synthetic xanthanolides did not show any activity
      against methicillin-resistant Staphylococcus aureus (MRSA), some of the synthetic
      intermediates did exhibit moderate antimicrobial activities.

PMID- 22850910
TI  - [IgA nephropathy: histological analysis and clinicomorfological correlation in
      patients from Minas Gerais State].
AB  - INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulopathy.
      OBJECTIVE: Classify IgAN according to the new Oxford's classification. METHODS:
      We analyzed the renal biopsies from the Nephropathology Service of UFTM, among
      1996 to 2010, with a diagnosis of IgAN. We assessed gender, age, presence of
      hematuria, patterns/intensity of the lesions, deposition of IgA, IgG, IgM, Kappa,
      Lambda, C3, C1q and fibrinogen. Based on the histological alterations, the
      biopsies were characterized according to the Oxford Classification, and the
      clinicomorfological correlation was made. Significative results for p < 0,05.
      RESULTS: A total of 164 cases biopsies, predominantly male (53.7%) and adults
      (93.3%). We characterized the patients according Oxford Classification, there was
      a predominance of the pattern M0 (85,3%), S1 (53,1%), E0 (65,2%) e T0 (70,1%).
      About the clinicomorfological correlation, we observed more severe proteinuria
      comparing M1 to M0 (p < 0,008), low estimated GFR (p < 0,001) and more frequent
      hypertension (p < 0,001) comparing T0, T1 e T2. On immunofluorescence, there is a
      predominance of IgA (100% of cases), with co-deposition of C3 (99.37% of cases),
      Kappa (96.25%), Lambda (91.25%) and IgM (76.92%). Correlation was found between
      IgA intensity and C3, Kappa and Lambda. CONCLUSION: In this study, IgA
      nephropathy was predominant in males, the more frequent patterns were the M0, S1,
      E0 and T0, with more severe proteinuria and the enhance of mesangial
      hypercellularity, besides larger prevalence of hypertension/worse kidney function
      according the tubulo-interstitial injuries.

PMID- 22850911
TI  - [Adherence to pharmacological treatment in adult patients undergoing
      hemodialysis].
AB  - INTRODUCTION: Adherence to treatment in patients on hemodialysis is not a simple
      process. Strategies to promote adherence will meet the need for improvements in
      the process of orientation concerning the disease and its pharmacological
      treatment. OBJECTIVES: To identify compliance with pharmacological treatment of
      patients on hemodialysis and the main factors related to it we used the Adherence
      Scale. METHODS: Observational, descriptive and cross-sectional study. Interviews
      were conducted to collect socioeconomic, pharmacological data, as well as those
      regarding self-reported adherence to drug. RESULTS: Out of the 65 participants,
      55.4% showed non-compliance. The mean number of drugs used was 4.1 +/- 2.5 (self
      report) and 6.2 +/- 3.0 (prescription). Statistical analysis showed significant
      differences concerning compliance at different ages (> 60 years are more
      adherent). CONCLUSIONS: A significant proportion of patients have difficulty to
      comply with treatment and the main factor was forgetfulness. Regarding age,
      elderly patients are more adherent to treatment. The low level of knowledge about
      the used drugs may be one of the reasons for the lack of adherence, and the
      patient's orientation process by a team of multiprofessionals involved in
      assisting is a strategy to promote adherence.

PMID- 22850908
TI  - Do bisphosphonates cause femoral insufficiency fractures?
AB  - In recent years, several reports have suggested an association between the use of
      bisphosphonates and subtrochanteric insufficiency fractures. Research from animal
      studies and in some cases from histomorphometric data collected from patients
      provide evidence of a possible pathophysiological mechanism behind this
      phenomenon. Despite this, it has not yet been possible to confirm a causal
      relationship. The small number of cases, the lack of consistency in defining
      these atypical fractures, the absence of homogeneity between studies, and the
      fact that most data available are derived from retrospective observational
      studies, are some of the difficulties encountered in the evaluation of evidence.
      Despite the proven benefit of bisphosphonates at providing protection against
      osteoporotic fractures, caution should be used before continuing therapy for
      longer than 5 years.

PMID- 22850912
TI  - [Prevalence of diabetes mellitus in chronic renal failure patients under
      haemodialysis in Porto Alegre, Brazil].
AB  - INTRODUCTION: The most common cause of chronic renal failure (CRF) among patients
      who are starting on dialysis in developed countries is diabetes mellitus (DM),
      with growing rates approaching 50%. In Brazil, the available data indicate a
      lower prevalence, around 27%, even though it is also increasing. OBJECTIVES: To
      estimate the prevalence of DM in the adult population of patients on hemodialysis
      for CRF in Porto Alegre, Brazil. METHODS: Cross-sectional, descriptive,
      quantitative and analytical survey study on the prevalence of DM among the 1,288
      patients on hemodialysis (HD) in all the 15 clinics in the city from June to
      July, 2009. RESULTS: 488 diabetic patients were identified, a prevalence of
      37.9%, ranging from 21 - 75% in the different clinics of the city. CONCLUSIONS:
      The prevalence of DM among chronic HD patients in Porto Alegre is higher than
      what was previously published as a cause of CRF in the country, which indicates
      the possibility that this etiology of CRF may have been underestimated.

PMID- 22850913
TI  - [Acute kidney injury in hospitalized patients with decompensated heart failure].
AB  - INTRODUCTION: Acute kidney injury (AKI) occurs frequently in critical patients,
      but its clinical relevance has not been determined in decompensated heart failure
      (DHF). OBJECTIVES: To study the occurrence and prognostic value of AKI in
      patients with DHF and to compare the clinical and laboratory characteristics and
      in-hospital mortality with those without AKI. METHODS: Prospective study of 85
      patients hospitalized in intensive care unit (ICU) with DHF from March 2010 to
      February 2011. Diagnosis of heart failure (HF) was established using the Boston
      criteria (scale > 8) and additional tests, and AKI was defined using the AKIN
      classification. Patients data with and without AKI were compared using Student's
      t-test, chi-squared statistic and multiple logistic regression, considering
      statistically significant p < 0.05. RESULTS: Most patients were male (55%),
      valvular disease was the main etiology of HF (42.4%), and inadequate medication
      was the main cause of decompensation (22.4%). AKI occurred in 76.5% of patients
      (4.7% stage 1, 32.9% stage 2 and 38.8% stage 3). Patients were more anemic (p =
      0.01) and had over 60 years (p = 0.02) in the AKI-group when compared to control.
      All patients with chronic kidney failure developed AKI. The duration of ICU stay
      was longer for the AKI group (group AKI 8.8 +/- 6.6 days; group non-AKI 4 +/- 1.4
      days, p < 0.01). In-hospital mortality rate was higher in patients with AKI (p =
      0.04), especially in stage 3 (p < 0.01). The duration of ICU stay was an
      independent predictor of AKI (p = 0.02). Only AKI was considered as independent
      predictor of mortality in this group (p = 0,05). CONCLUSION: AKI is frequent in
      DHF, especially in advanced stages, in the elderly and patients with chronic
      kidney disease, and was associated with longer hospitalization and higher
      mortality rate.

PMID- 22850914
TI  - [Efect of short term glycemic control on microalbuminuria and glomerular
      filtration rate in type 2 diabetic patients with poor glycemic control].
AB  - INTRODUCTION: The intensive glucose control significantly reduces the risk of
      microvascular complications, including nephropathy. OBJECTIVES: We assess the
      impact of glycemic control through calculation of weekly mean glycemia (WMG) and
      glycemic variability (GV) on 24 hours ambulatory blood pressure (ABPM), urinary
      albumin excretion (UAE) and glomerular filtration rate (GFR). METHODS: 53
      patients with type 2 diabetes mellitus (DM2) were randomly divided into two
      groups to receive conventional or intensive treatment, which included weekly
      visits for medication adjustments and implementation of an educational plan for
      six weeks. RESULTS: We observed glycemic control (WMG < 150 mg/dL and VG < 50) in
      75% (n = 21) of the patients on the intervention treatment (IT) (n = 28), and in
      24% (n = 6) of the ones on the conventional treatment (CT) (n = 25) (p < 0.001).
      Considering patients of the two groups, 14 out of the 27 patients who achieved
      glycemic control showed initial mean systolic blood pressure (SBP) > 120 mmHg
      which was reduced from 138.4 +/- 10.1 to 127.8 +/- 11.6 mmHg (p = 0.023) at the
      end of week six. Reductions in SBP and diastolic BP (DBP) during wakefulness and
      sleep did not occur in the group (n = 17) without glycemic control and with SBP >
      120 mmHg. Initially, 15 patients had GFR > 120 mL/min, and after six weeks, only
      the subgroup that achieved glycemic control (n = 7) showed a reduction of 137.2
      +/- 16 to 122.2 +/- 25.2 mL/min (p = 0.02). At the beginning of the study,
      another fifteen patients presented with microalbuminuria. After six weeks,
      regardless of whether they achieved glycemic control or not, there was reduction
      in UAE, from 63.0 +/- 43.1 to 24.8 +/- 19.5 mg/g creatinine (p = 0.02).
      CONCLUSION: Thus short term glycemic control resulted in reductions of BP, GFR
      and the UAE in patients with DM2, which are beneficial for renal protection.

PMID- 22850915
TI  - Impact of training at ventilatory threshold on cardiopulmonary and functional
      capacity in overweight patients with chronic kidney disease.
AB  - INTRODUCTION: Chronic kidney disease (CKD) and obesity are both associated with
      reduced physical capacity. The potential benefit of aerobic training on physical
      capacity has been recognized. The exercise intensity can be established using
      different methods mostly subjective or indirect. Ventilatory threshold (VT) is a
      direct and objective method that allows prescribing exercise intensity according
      to individual capacity. OBJECTIVES: To evaluate the impact of aerobic training at
      VT intensity on cardiopulmonary and functional capacities in CKD patients with
      excess of body weight. METHODS: Ten CKD patients (eight men, 49.7 +/- 10.1 years;
      BMI 30.4 +/- 3.5 kg/m2, creatinine clearance 39.4 +/- 9.8 mL/min/1.73 m2)
      underwent training on a treadmill three times per week during 12 weeks.
      Cardiopulmonary capacity (ergoespirometry), functional capacity and clinical
      parameters were evaluated. RESULTS: At the end of 12 weeks, VO2PEAK increased by
      20%, and the speed at VO2PEAK increased by 16%. The training resulted in
      improvement in functional capacity tests, such as six-minute walk test (9.2%),
      two-minute step test (20.3%), arm curl test (16.3%), sit and stand test (35.7%),
      and time up and go test (15.3%). In addition, a decrease in systolic and
      diastolic blood pressures was observed despite no change in body weight, sodium
      intake and antihypertensive medication. CONCLUSION: Aerobic exercise performed at
      VT intensity improved cardipulmonary and functional capacities of overweight CKD
      patients. Additional benefit on blood pressure was observed. These results
      suggest that VT can be effectively applied for prescribing exercise intensity in
      this particular group of patients.

PMID- 22850916
TI  - Uremic pruritus in hemodialysis patients: treatment with desloratidine versus
      gabapentin.
AB  - INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective
      treatments are not readily available. Early evidence with antihistamines and
      gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side
      effects of gabapentin and desloratadine in patients with dialysis pruritus.
      METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on
      chronic hemodialysis with sustained pruritus over a period of at least 60 days.
      After a one-week run-in period, we assigned patients to three weeks of either
      gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one
      week washout period, each patient crossed-over to the alternate regimen for three
      more weeks. The primary endpoint of the study was the change in the visual
      analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two
      treatment blocks and were available for analysis. VAS scores decreased with both
      treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with
      desloratadine, p = 0.004), but only desloratadine reached statistical
      significance. There were no differences when comparing the final pruritus score
      with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation
      was common with gabapentin. Desloratadine was well tolerated. CONCLUSION:
      Desloratadine provides significant relief of uremic pruritus compared with no
      therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than
      gabapentin.

PMID- 22850917
TI  - [Prevalence of frailty in patients in chronic kidney disease on conservative
      treatment and on dialysis].
AB  - INTRODUCTION: Frailty is a physiological vulnerability status of the patient
      which is associated with the increased number of hospitalization and death.
      OBJECTIVES: To evaluate the prevalence of frailty and its associated factors in
      patients with chronic kidney disease (CKD) on conservative treatment (CT),
      hemodialysis (HD) and peritoneal dialysis (PD). METHODS: Frailty was assessed in
      146 patients (86 CT, 37 HD and 23 PD) and characterized as muscle weakness and
      exhaustion--by the physical aspect and vitality domains, respectively, evaluated
      in the SF-36 quality of life instrument; physical inactivity--if he or she
      answered "never" or "hardly ever" when asked about physical activity; and as
      unintentional weight loss (> 4.5 kg per year). Patients were divided into three
      groups: non-fragile (NF), pre-fragile (PF) and fragile (F). The demographic,
      clinical and laboratory data were extracted from patient charts. RESULTS: Frailty
      was diagnosed in 36% of patients on CT, 37.8% in HD and 47.8% in PD. It was
      characterized in 36.8% of patients aged between 20 and 40 years and 40.3% of
      those between 41 and 60 years. Frailty was significantly associated with the use
      of vitamin D (r = 0.16; p = 0.03), hemoglobin (r = -0.14; p = - 0.02) and intact
      parathyroid hormone (r = 0.16; p = 0.03). CONCLUSIONS: Frailty is common among
      patients with CKD on conservative treatment and dialysis, even in those who are
      not elderly. In the patients studied, the phenotype of frailty was associated
      with no usage of vitamin D, lower serum levels of hemoglobin and higher levels of
      parathyroid hormone.

PMID- 22850918
TI  - [Echocardiographic associations with renal function in hypertensive individuals
      treated at primary care level].
AB  - INTRODUCTION: Microalbuminuria (MA) and glomerular filtration rate (GFR) can be
      associated with cardiac complications hypertension (AH), which may lead to
      changes in the structure, function and left ventricular geometry. OBJECTIVES: To
      correlate changes of the GFR and MA with the parameters of the left ventricle
      (LV) assessed by echocardiography. METHODS: A cross-sectional study was carried
      out from February through July 2010 with 220 hypertensive patients treated at two
      Primary Care Outpatient Clinics in Sao Luis. Patients > 18 years of age of both
      sexes were included in the study. Sociodemographic data, GFR, MA on 24-hour
      urine, biochemistry and LV geometry and function were assessed. They were divided
      into two groups according to MA and GFR. RESULTS: The group AH and MA showed
      increased wall thickness and LV mass indexed for the body surface area (BSA) and
      relative wall thickness (RWT), lower lateral E' and septal waves, and higher mean
      E/e' ratio (p <0.05). The AH group with GFR < 60 mL/min/1,73 m2 showed increased
      wall thickness and LV mass indexed for BSA, lower lateral E 'and septal waves,
      and higher mean E/e' ratio (p < 0.05). The geometric pattern of LV concentric
      hypertrophy (LVH) was related to MA (p = 0.002). CONCLUSIONS: The MA was
      significantly associated with increased LV wall thickness and LV mass indexed for
      BSA, and also changes of diastolic function. Left ventricular concentric
      hypertrophy was related to MA. The GFR was also significantly associated with
      increased LV wall thickness and LV mass indexed for BSA suggesting changes of the
      diastolic function.

PMID- 22850919
TI  - [Nutritional status and food intake of continuous peritoneal dialysis patients
      with and without secondary hyperparathyroidism].
AB  - INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a common and early
      complication in chronic kidney disease (CKD) patients. Studies have suggested
      that high levels of parathyroid hormone (PTH) may have deleterious effects on the
      nutritional status of patients with CKD. Thus, the aim of this study was to
      compare the nutritional status of CKD patients in continuous peritoneal dialysis
      (CPD) with and without SHPT. OBJECTIVE: The aim of this study was to compare the
      nutritional status of CKD patients in continuous peritoneal dialysis (CPD) with
      and without SHPT. METHODS: 74 patients were evaluated, including adults and
      seniors, divided into two groups according to PTH levels. In group 1 (n = 18)
      levels of PTH higher than 300 pg/mL and in group 2 less than or equal to 300
      pg/mL. The nutritional status of patients was assessed by anthropometry,
      biochemical and subjective global assessment (SGA). Food intake was measured by
      food record for 3 days. We also collected clinical data, such as calcium and
      serum phosphorus, and the presence of inflammation was assessed by measuring C
      reactive protein ultra-sensitive (CRP US). RESULTS: The average age of the
      population studied was 54.97 +/- 17.06 years, with predominance of adult patients
      (58.1%) and females (56.8%). The time of CPD expressed in median was 17 months
      (7.75-33). Through ASG, it was shown a prevalence of 36.5% of the population
      undernourished. In the analysis of difference between the groups in relation to
      anthropometry, biochemical indicators and ASG as well as food intake, there were
      no differences between the groups. CONCLUSION: There were no differences in
      nutritional status and dietary intake between patients with and without SHPT.

PMID- 22850920
TI  - [Use of vaccines for prophylaxis of urinary tract infections].
AB  - The urinary tract is the most common site of bacterial infections. Urinary tract
      infections (UTIs) in women without urinary tract anatomic abnormalities require
      frequent and repeated use of antibiotics, increasing the prevalence of
      antimicrobial-resistant microorganisms. The possibility of an alternative
      approach, with the use of vaccines produced from inactivated bacteria or
      structural components of these microorganisms, is a reality. Confirming the
      results observed experimentally, controlled clinical studies of oral or vaginal
      immunotherapy have shown reductions in the number of episodes of recurrence,
      without significant side-effects. We reviewed the mechanisms of aggression and
      defense involved in the pathogenesis of UTIs in women with anatomically normal
      urinary tracts, the evolution of knowledge about the immunotherapy of UTIs, and
      the vaccines already available or under development for the treatment of this
      important clinical condition.

PMID- 22850921
TI  - [Crosstalk between bone and adipose tissue in chronic kidney disease].
AB  - Within the concept that hormones are regulated by a cycle of reciprocity, the
      fact that osteoblasts and adipocytes are developed from mesenchymal stem cells
      and that bone remodeling is regulated by leptin brings up the idea of possible
      bone participation in energy metabolism and vice-versa. Recent studies have shown
      that the differentiation and function of these bone cells are regulated by
      leptin, which seems to trigger a bimodal response, via sympathetic nervous
      system, and a local response, in which leptin acts on the bone. In fact, studies
      have shown complex interactions between bone, adipose tissue and brain. However,
      there are few studies on crosstalk in patients with chronic kidney disease (CKD).
      These patients have a tendency to decreased bone mineral density and high levels
      of leptin. Then, this article presented a review of potential involvement of
      adipose tissue and bone mass in patients with CKD.

PMID- 22850922
TI  - [Effects of aerobic exercise during haemodialysis in patients with chronic renal
      disease: a literature review].
AB  - INTRODUCTION: Patients with chronic kidney disease (CKD) have reduced physical
      and functional capacity when compared with the general population. Hemodialysis
      (HD) restricts patients activities, favoring a sedentary lifestyle and leading to
      functional limitations. HD patients are less active, present low exercise
      tolerance and have high physical deconditioning. Physical exercise programs have
      been proposed as a strategy not only to treat clinical symptoms, but also to
      reduce physical limitations and improve the quality of life of these patients.
      OBJECTIVES: The purpose of this study was to review the literature on the effects
      of physical exercise (aerobic exercise on a cycle ergometer for the lower limbs)
      on CKD undergoing HD. METHODS: The Medline, PubMed, Scielo, Embase and
      DirectScience databases were searched. RESULTS: Fourteen randomized controlled
      clinical trials were analyzed as regards the timing of the intervention during
      the HD session, exercise intensity and frequency, the duration of the
      intervention and the main results. CONCLUSION: The studies demonstrated that
      aerobic exercises performed during HD improve the aerobic capacity and physical
      conditioning, reduce fatigue and anxiety, improve muscle capillarization and
      resting blood pressure, increase exercise duration and improve urea clearance.

PMID- 22850923
TI  - [Nutcraker syndrome as a cause of recurrent hematuria in a young woman: a case
      report].
AB  - INTRODUCTION: The nutcracker syndrome is defined by the compression of the left
      renal vein between the aorta and superior mesenteric arteries, accompanied by a
      classic, but less specific, symptomatology. CASE REPORT: We reported a case of a
      37-year-old woman who had been investigated because of intermittent gross
      hematuria of unknown origin. Computed tomographic angiography revealed
      compression of the left renal vein as it ran between the superior mesenteric
      artery and the abdominal aorta, associated with significant dilation of the left
      ovarian vein. DISCUSSION: The nutcracker syndrome, caused by compression of the
      left renal vein by the aorta and superior mesenteric arteries, is probably more
      prevalent in women, and it is caused by specific situations, such as renal ptosis
      and paucity of retroperitoneal fat. Hematuria, a typical symptom, is due to
      rupture of the thin-walled septum separating the veins of the urinary collecting
      system. Imaging tests may help with the diagnosis. The best treatment is still
      elusive, but there are several surgical approaches, such as intravascular
      stenting, and also a conservative management. Diagnosis is usually delayed, and
      the syndrome should be included in the differential of hematuria of unknown
      origin.

PMID- 22850924
TI  - [Guidelines on bone mineral disorder in chronic kidney disease--addendum chapter
      2].

PMID- 22850926
TI  - Flexibility and swing effect on the adsorption of energy-related gases on ZIF-8:
      combined experimental and simulation study.
AB  - ZIF-8, a prototypical zeolitic porous coordination polymer, prepared via the self
      assembly of tetrahedral atoms (e.g. Zn and Co) and organic imidazolate linkers,
      presents large cavities which are interconnected by narrow windows that allow, in
      principle, molecular sieving. However, ZIF-8 shows flexibility due to the swing
      of the imidazolate linkers, which results in the adsorption of molecules which
      are too large to fit through the narrow window. In this work, we assess the
      impact of this flexibility, previously only observed for nitrogen, and the level
      of agreement between the experimental and simulated isotherms of different energy
      related gases on ZIF-8 (CO(2), CH(4) and alkanes). We combine experimental gas
      adsorption with GCMC simulations, using generic and adjusted force fields and DFT
      calculations with the Grimme dispersion correction. By solely adapting the UFF
      force field to reduce the Lennard-Jones parameter epsilon, we achieve excellent
      agreement between the simulated and experimental results not only for ZIF-8 but
      also for ZIF-20, where the transferability of the adapted force field is
      successfully tested. Regarding ZIF-8, we show that two different structural
      configurations are needed to properly describe the adsorption performance of this
      material, demonstrating that ZIF-8 is undergoing a structural change during gas
      adsorption. DFT calculations with the Grimme dispersion correction are consistent
      with the GCMC and experimental observations, illustrating the thermodynamics of
      the CH(4) adsorption sites and confirming the existence of a new adsorption site
      with a high binding energy within the 4-ring window of ZIF-8.

PMID- 22850925
TI  - Using prediction errors to drive saccade adaptation: the implicit double-step
      task.
AB  - A prediction-based error signal, neurally computed as the difference between
      predicted and observed movement outcomes, has been proposed as the driving force
      for motor learning. This suggests that the generation of predictive saccades to
      periodically paced targets-whose performance accuracy is actively maintained
      using this same error signal-invokes the motor-learning network. We examined
      whether a simple predictive-saccade task (implicit double-step adaptation, in
      which targets are gradually displaced outward to exaggerate normal hypometric
      movement errors) can stand in place of a traditional double-step saccade
      adaptation task to induce an increase in saccade gain. We find that the implicit
      double-step adaptation task can induce significant gain-increase adaptation (of
      comparable magnitude to that of the standard double-step task) in normal control
      subjects. Unlike control subjects, patients with impaired cerebella are unable to
      adapt their saccades in response to this paradigm; this implies that the
      cerebellum is crucial for processing prediction-based error signals for motor
      learning.

PMID- 22850927
TI  - Synthesis and preliminary biological evaluation of carba analogues from Neisseria
      meningitidis A capsular polysaccharide.
AB  - The Gram-negative encapsulated bacterium Neisseria meningitidis type A (MenA) is
      a major cause of meningitis in developing countries, especially in the sub
      Saharan region of Africa. The development and manufacture of an efficient
      glycoconjugate vaccine against MenA is greatly hampered by the poor hydrolytic
      stability of its capsular polysaccharide, consisting of (1->6)-linked 2-acetamido
      2-deoxy-alpha-d-mannopyranosyl phosphate repeating units. The replacement of the
      ring oxygen with a methylene group to get a carbocyclic analogue leads to the
      loss of the acetalic character of the phosphodiester and consequently to the
      enhancement of its chemical stability. Here we report the synthesis of oligomers
      (mono-, di- and trisaccharide) of carba-N-acetylmannosamine-1-O-phosphate as
      candidates for stabilized analogues of the corresponding fragments of MenA
      capsular polysaccharide. Each of the synthesized compounds contains a
      phosphodiester-linked aminopropyl spacer at its reducing end to allow for protein
      conjugation. The inhibition abilities of the synthetic molecules were
      investigated by a competitive ELISA assay, showing that only the carba
      disaccharide is recognized by a polyclonal anti-MenA serum with an affinity
      similar to a native MenA oligosaccharide with average polymerization degree of 3.

PMID- 22850929
TI  - Quantification of left ventricular volume and global function using a fast
      automated segmentation tool: validation in a clinical setting.
AB  - Real-time 3D echocardiography (RT3DE) has already been shown to be an accurate
      tool for left ventricular (LV) volume assessment. However, LV border detection in
      RT3DE remains a time-consuming task jeopardizing the application of this modality
      in routine practice. We have recently developed a 3D automated segmentation
      framework (BEAS) able to capture the LV morphology in real-time. The goal of this
      study was to assess the accuracy of this approach in extracting volumetric
      parameters in a clinical setting. 24 RT3DE exams were acquired in a group of
      healthy volunteers (# = 5) and diseased patients (# = 19), with LV
      volume/function within a range typically measured in a clinical setting. End
      diastolic and end-systolic volumes (EDV, ESV) were manually contoured by 3 expert
      sonographers from which the stroke volume and ejection fraction (SV, EF) were
      calculated. The values extracted with BEAS were compared to the average of the 3
      experts measurements using correlation and Bland-Altman statistics. Linear
      regression analysis showed a strong correlation between the automated algorithm
      and the reference values (R = 0.963, 0.947, 0.944 and 0.853 for EDV, ESV, SV and
      EF respectively). Bland-Altman analysis revealed a bias (limits of agreement) of
      2.59 (-25.39, 30.57) ml, -2.11 (-24.91, 20.69) ml, 4.70 (12.93, 22.34) ml and
      3.45 (-8.96, 15.87) %, for EDV, ESV, SV and EF respectively. Total analysis time
      using BEAS was 30.7 +/- 7.5 s. BEAS allows for a fast and accurate quantification
      of 3D cardiac volumes and global function with minimal user input. It may
      therefore contribute to the integration of 3D echocardiography in routine
      clinical practice.

PMID- 22850930
TI  - Capability of three-dimensional speckle tracking radial strain for identification
      of patients with cardiac sarcoidosis.
AB  - Since cardiac sarcoidosis (CS) leads to substantial morbidity and sudden death,
      early diagnosis and appropriate management are crucial for patients with CS.
      Echocardiography used to be considered a useful diagnostic tool for patients with
      CS, but CS may clinically present as dilated cardiomyopathy (DCM). Our objective
      was to investigate whether a novel three-dimensional (3-D) speckle-tracking
      strain can identify patients with CS more accurately. We studied 23 CS patients
      with an ejection fraction (EF) of 46 +/- 10 %, and 16 EF-matched patients with
      DCM (EF 45 +/- 11 %). Global radial (GRS), circumferential (GCS) and longitudinal
      (GLS) strain was assessed using 3-D speckle-tracking system. GRS of patients with
      CS was significantly lower than that of patients with DCM (18.5 +/- 8.4 vs. 28.5
      +/- 8.3 %, p < 0.01), but GCS and GLS in patients with CS and DCM were similar.
      GRS ? 21.1 could differentiate CS from DCM with a sensitivity of 70 %,
      specificity of 88 % and area under the curve of 0.79. An additional noteworthy
      findings was that, patients with CS showed more negative radial strain curves
      than did those with DCM (1.7 +/- 2.3 vs. 0.1 +/- 0.5, p < 0.01). In conclusion, 3
      D speckle-tracking radial strain shows good potential to distinguish CS from DCM.
      Our observations can thus be expected to have clinical implications for
      management of CS patients.

PMID- 22850931
TI  - Investigations on silver/polyaniline electrodes for electrochemical
      supercapacitors.
AB  - Polyaniline (PANI) and silver doped polyaniline (Ag/PANI) thin films were
      deposited on stainless steel substrates by a dip coating technique. To study the
      effect of doping concentration of Ag on the specific capacitance of PANI the
      concentration of Ag was varied from 0.3 to 1.2 weight percent. Fourier transform
      infrared and Fourier transform-Raman spectroscopy, and energy dispersion X-ray
      techniques were used for the phase identification and determination of the doping
      content in the PANI films, respectively. The surface morphology of the films was
      examined by Field Emission Scanning Electron Microscopy, which revealed a
      nanofiber like structure for PANI and nanofibers with bright spots of Ag
      particles for the Ag/PANI films. There was decrease in the room temperature
      electrical resistivity of the Ag/PANI films of the order of 10(2) with increasing
      Ag concentration. The supercapacitive behavior of the electrodes was tested in a
      three electrode system using 1.0 M H(2)SO(4) electrolyte. The specific
      capacitance increased from 285 F g(-1) (for PANI) to 512 F g(-1) for Ag/PANI at
      0.9 weight percent doping of Ag, owing to the synergic effect of PANI and silver
      nanoparticles. This work demonstrates a simple strategy of improving the specific
      capacitance of polymer electrodes and may also be easily adopted for other
      dopants.

PMID- 22850932
TI  - Anxiety, sensory over-responsivity, and gastrointestinal problems in children
      with autism spectrum disorders.
AB  - Children with autism spectrum disorders (ASD) experience high rates of anxiety,
      sensory processing problems, and gastrointestinal (GI) problems; however, the
      associations among these symptoms in children with ASD have not been previously
      examined. The current study examined bivariate and multivariate relations among
      anxiety, sensory over-responsivity, and chronic GI problems in a sample of 2,973
      children with ASD enrolled in the Autism Treatment Network (ages 2-17 years, 81.6
      % male). Twenty-four percent of the sample experienced at least one type of
      chronic GI problem (constipation, abdominal pain, bloating, diarrhea, and/or
      nausea lasting three or more months). Children with each type of GI problem had
      significantly higher rates of both anxiety and sensory over-responsivity. Sensory
      over-responsivity and anxiety were highly associated, and each provided unique
      contributions to the prediction of chronic GI problems in logistic regression
      analyses. The results indicate that anxiety, sensory over-responsivity and GI
      problems are possibly interrelated phenomenon for children with ASD, and may have
      common underlying mechanisms.

PMID- 22850933
TI  - Properties of noise in positron emission tomography images reconstructed with
      filtered-backprojection and row-action maximum likelihood algorithm.
AB  - Noise levels observed in positron emission tomography (PET) images complicate
      their geometric interpretation. Post-processing techniques aimed at noise
      reduction may be employed to overcome this problem. The detailed characteristics
      of the noise affecting PET images are, however, often not well known. Typically,
      it is assumed that overall the noise may be characterized as Gaussian. Other PET
      imaging-related studies have been specifically aimed at the reduction of noise
      represented by a Poisson or mixed Poisson + Gaussian model. The effectiveness of
      any approach to noise reduction greatly depends on a proper quantification of the
      characteristics of the noise present. This work examines the statistical
      properties of noise in PET images acquired with a GEMINI PET/CT scanner. Noise
      measurements have been performed with a cylindrical phantom injected with (11)C
      and well mixed to provide a uniform activity distribution. Images were acquired
      using standard clinical protocols and reconstructed with filtered-backprojection
      (FBP) and row-action maximum likelihood algorithm (RAMLA). Statistical properties
      of the acquired data were evaluated and compared to five noise models (Poisson,
      normal, negative binomial, log-normal, and gamma). Histograms of the experimental
      data were used to calculate cumulative distribution functions and produce maximum
      likelihood estimates for the parameters of the model distributions. Results
      obtained confirm the poor representation of both RAMLA- and FBP-reconstructed PET
      data by the Poisson distribution. We demonstrate that the noise in RAMLA
      reconstructed PET images is very well characterized by gamma distribution
      followed closely by normal distribution, while FBP produces comparable conformity
      with both normal and gamma statistics.

PMID- 22850934
TI  - Investigation of the variability in the assessment of digital chest X-ray image
      quality.
AB  - A large database of digital chest radiographs was developed over a 14-month
      period. Ten radiographic technologists and five radiologists independently
      evaluated a stratified subset of images from the database for quality
      deficiencies and decided whether each image should be rejected. The evaluation
      results showed that the radiographic technologists and radiologists agreed only
      moderately in their assessments. When compared against each other, radiologist
      and technologist reader groups were found to have even less agreement than the
      inter-reader agreement within each group. Radiologists were found to be more
      accepting of limited-quality studies than technologists. Evidence from the study
      suggests that the technologists weighted their reject decisions more heavily on
      objective technical attributes, while the radiologists weighted their decisions
      more heavily on diagnostic interpretability relative to the image indication. A
      suite of reject-detection algorithms was independently run on the images in the
      database. The algorithms detected 4 % of postero-anterior chest exams that were
      accepted by the technologist who originally captured the image but which would
      have been rejected by the technologist peer group. When algorithm results were
      made available to the technologists during the study, there was no improvement in
      inter-reader agreement in deciding whether to reject an image. The algorithm
      results do, however, provide new quality information that could be captured
      within a site-wide, reject-tracking database and leveraged as part of a site-wide
      QA program.

PMID- 22850935
TI  - What is needed to keep persons with multiple sclerosis vitamin D-sufficient
      throughout the year?
AB  - Vitamin D sufficiency has been associated with lower risk of multiple sclerosis
      and may also have a favorable effect on the course of the disease. The aim of
      this work was to identify predictors of serum 25-hydroxy vitamin D (25[OH]D)
      levels in persons with multiple sclerosis (MS) and to assess the effect of high
      dose vitamin D(3) supplementation on vitamin D status. A 96-week randomized
      controlled trial was performed to assess the effect of supplementation with
      20,000 IU of vitamin D(3) weekly on bone mineral density in 68 patients. We
      collected data on vitamin D intake and UV-exposure and repeatedly measured serum
      25(OH)D levels. Half of the participants had sufficient winter vitamin D levels
      at baseline (>= 50 nmol/l). Vitamin D status was predicted by sun exposure during
      the last 3 months and by ingested vitamin D from diet and supplements. In the
      placebo group, the proportion of the participants with sufficient levels
      increased from 55 % in winter to 92 % during the summer. In the intervention
      group, all participants had winter 25(OH)D levels above 50 nmol/l at the end of
      the study. MS patients who have no sun exposure and low dietary vitamin D intake
      during the winter months should be recommended to take vitamin D supplements to
      achieve serum 25(OH)D levels of at least 50 nmol/l.

PMID- 22850936
TI  - Cognitive and MRI correlates of orthostatic hypotension in Parkinson's disease.
AB  - Orthostatic hypotension (OH) is a frequent nonmotor feature of Parkinson's
      disease (PD), and its occurrence has been associated with cognitive impairment.
      The underlying mechanism could be mediated by development of cerebrovascular
      disease induced by chronic or episodic hypoperfusion, but the extent of brain
      vascular load in PD patients with OH has never been investigated. This study
      aimed to assess the relationship between OH and cognitive function in PD patients
      and to investigate the contribution of brain vascular lesions. Forty-eight PD
      patients underwent a tilt table test (TT) to assess supine and orthostatic blood
      pressure  as well as an extensive neuropsychological evaluation to evaluate
      cognitive function. Brain magnetic resonance imaging was acquired in 44/48
      patients and analyzed by a visual semiquantitative scale. Twenty-three patients
      presented OH at TT (13/23 were symptomatic), and 25 did not. There were no
      differences in motor severity or disease duration between patients with and
      without OH. In patients with OH we found significantly worse cognitive
      performance in specific tasks, such as sustained attention, visuospatial and
      verbal memory, compared with patients without OH. However, there were no
      differences in vascular burden between the two groups. Our study confirms that
      there is an association between OH and selective cognitive deficits in PD, but
      rebuts the hypothesis that this is underlined by the development of
      cerebrovascular disease.

PMID- 22850937
TI  - Globus pallidus and substantia nigra hypointensities on T2-weighted imaging in
      MELAS.

PMID- 22850939
TI  - Arabidopsis light-dependent NADPH: protochlorophyllide oxidoreductase A (PORA) is
      essential for normal plant growth and development: an addendum.
AB  - Recently the porA-1 null mutant of Arabidopsis thaliana has been identified,
      which contains an insertion of the Dissociation (Ds) element in the PORA gene
      (Paddock et al. in Plant Mol Biol 78:447-460, 2012). Light-grown porA-1 seedlings
      suffer from a drastically reduced chlorophyll content and a developmental arrest
      beyond the cotyledon stage, suggesting that PORA is not only transiently involved
      in initiating chlorophyll synthesis during illumination of etiolated seedlings
      but is also essential for normal growth and plant development. Here we report the
      presence of a second Ds element in this porA-1 mutant line that inactivates the
      Speechless gene required for stomata formation. Similar to porA-1, speechless
      seedlings are severely impaired in their development. Our results suggest that
      the lack of stomata in porA-1 may contribute to the dwarfed phenotype of the
      mutant and thus emphasizes the need to re-address the proposed role of PORA
      during plant development by studying a porA mutant that retains its stomata
      formation.

PMID- 22850943
TI  - Professor philip sambrook - obituary.

PMID- 22850940
TI  - Biomechanical evaluation of a low profile, anchored cervical interbody spacer
      device in the setting of progressive flexion-distraction injury of the cervical
      spine.
AB  - INTRODUCTION: Anterior cervical decompression and fusion is a well-established
      procedure for treatment of degenerative disc disease and cervical trauma
      including flexion-distraction injuries. Low-profile interbody devices
      incorporating fixation have been introduced to avoid potential issues associated
      with dissection and traditional instrumentation. While these devices have been
      assessed in traditional models, they have not been evaluated in the setting of
      traumatic spine injury. This study investigated the ability of these devices to
      stabilize the subaxial cervical spine in the presence of flexion-distraction
      injuries of increasing severity. METHODS: Thirteen human cadaveric subaxial
      cervical spines (C3-C7) were tested at C5-C6 in flexion-extension, lateral
      bending and axial rotation in the load-control mode under +/-1.5 Nm moments. Six
      spines were tested with locked screw configuration and seven with variable angle
      screw configuration. After testing the range of motion (ROM) with implanted
      device, progressive posterior destabilization was performed in 3 stages at C5-C6.
      RESULTS: The anchored spacer device with locked screw configuration significantly
      reduced C5-C6 flexion-extension (FE) motion from 14.8 +/- 4.2 to 3.9 +/- 1.8
      degrees , lateral bending (LB) from 10.3 +/- 2.0 to 1.6 +/- 0.8, and axial
      rotation (AR) from 11.0 +/- 2.4 to 2.5 +/- 0.8 compared with intact under (p <
      0.01). The anchored spacer device with variable angle screw configuration also
      significantly reduced C5-C6 FE motion from 10.7 +/- 1.7 to 5.5 +/- 2.5 degrees ,
      LB from 8.3 +/- 1.4 to 2.7 +/- 1.0, and AR from 8.8 +/- 2.7 to 4.6 +/- 1.3
      compared with intact (p < 0.01). The ROM of the C5-C6 segment with locked screw
      configuration and grade-3 F-D injury was significantly reduced from intact, with
      residual motions of 5.1 +/- 2.1 in FE, 2.0 +/- 1.1 in LB, and 3.3 +/- 1.4 in AR.
      Conversely, the ROM of the C5-C6 segment with variable-angle screw configuration
      and grade-3 F-D injury was not significantly reduced from intact, with residual
      motions of 8.7 +/- 4.5 in FE, 5.0 +/- 1.6 in LB, and 9.5 +/- 4.6 in AR.
      CONCLUSIONS: The locked screw spacer showed significantly reduced motion compared
      with the intact spine even in the setting of progressive flexion-distraction
      injury. The variable angle screw spacer did not sufficiently stabilize flexion
      distraction injuries. The resulting motion for both constructs was higher than
      that reported in previous studies using traditional plating. Locked screw spacers
      may be utilized with additional external immobilization while variable angle
      screw spacers should not be used in patients with flexion-distraction injuries.

PMID- 22850938
TI  - Connexin- and pannexin-based channels in normal skeletal muscles and their
      possible role in muscle atrophy.
AB  - Precursor cells of skeletal muscles express connexins 39, 43 and 45 and
      pannexin1. In these cells, most connexins form two types of membrane channels,
      gap junction channels and hemichannels, whereas pannexin1 forms only
      hemichannels. All these channels are low-resistance pathways permeable to ions
      and small molecules that coordinate developmental events. During late stages of
      skeletal muscle differentiation, myofibers become innervated and stop expressing
      connexins but still express pannexin1 hemichannels that are potential pathways
      for the ATP release required for potentiation of the contraction response. Adult
      injured muscles undergo regeneration, and connexins are reexpressed and form
      membrane channels. In vivo, connexin reexpression occurs in undifferentiated
      cells that form new myofibers, favoring the healing process of injured muscle.
      However, differentiated myofibers maintained in culture for 48 h or treated with
      proinflammatory cytokines for less than 3 h also reexpress connexins and only
      form functional hemichannels at the cell surface. We propose that opening of
      these hemichannels contributes to drastic changes in electrochemical gradients,
      including reduction of membrane potential, increases in intracellular free Ca(2+)
      concentration and release of diverse metabolites (e.g., NAD(+) and ATP) to the
      extracellular milieu, contributing to multiple metabolic and physiologic
      alterations that characterize muscles undergoing atrophy in several acquired and
      genetic human diseases. Consequently, inhibition of connexin hemichannels
      expressed by injured or denervated skeletal muscles might reduce or prevent
      deleterious changes triggered by conditions that promote muscle atrophy.

PMID- 22850941
TI  - Quantitative analysis of tetracycline-inducible expression of the green
      fluorescent protein gene in transgenic chickens.
AB  - The use of transgenic farm animals as "bioreactors" to address the growing demand
      for biopharmaceuticals, both in terms of increased quantity and greater number,
      represents a key development in the advancement of medical science. However, the
      potential for detrimental side-effects as a result of uncontrolled constitutive
      expression of foreign genes in transgenic animals is a well-recognized limitation
      of such systems. Previously, using a tetracycline-inducible expression system, we
      demonstrated the induction of expression of a transgene encoding green
      fluorescent protein (GFP) in transgenic chickens by feeding with doxycycline, a
      tetracycline derivative; expression of GFP reverted to pre-induction levels when
      the inducer was removed from the diet. As a proof of principle study, however,
      quantitative assessment of expression was not possible, as only one G0 and one G1
      transgenic chicken was obtained. In the current study, a sufficient number of G2
      and G3 transgenic chickens were obtained, and quantification analysis
      demonstrated up to a 20-fold induction of expression by doxycycline. In addition,
      stable transmission of the transgene without any apparent genetic modifications
      was observed through several generations. The use of an inducible expression
      system that can be regulated by dietary supplementation could help mitigate the
      physiological disruption that can occur in transgenic animals as a result of
      uncontrolled constitutive expression of a transgene. Importantly, these results
      also support the use of the retroviral system for generating transgenic animals
      with minimal risk in terms of biosafety.

PMID- 22850944
TI  - Modular electron donor group tuning of frontier energy levels in
      diarylaminofluorenone push-pull molecules.
AB  - Push-pull organic molecules composed of electron donor diarylamines at the 2- and
      2,7-positions of fluorenone exhibit intramolecular charge-transfer behaviour in
      static absorption and emission spectra. Electrochemical and spectral data
      combined in a modular electronic analysis model show how the donor HOMO and
      acceptor LUMO act as major determinants of the frontier molecular orbital energy
      levels.

PMID- 22850945
TI  - An evaluation of p16(INK4a) expression in cervical intraepithelial neoplasia
      specimens, including women with HIV-1.
AB  - Although several studies have evaluated the role of p16(INK4a) as a diagnostic
      marker of cervical intraepithelial neoplasia (CIN) and its association with
      disease progression, studies regarding the role of p16(INK4a) in human
      immunodeficiency virus (HIV)-infected patients remain scarce. The present study
      was designed to determine the potential utility of p16(INK4a) as a diagnostic
      marker for CIN and invasive cervical cancer in HIV-positive and negative cervical
      specimens. An immunohistochemical analysis of p16(INK4a) was performed in 326
      cervical tissue microarray specimens. Performance indicators were calculated and
      compared using receiving operating characteristics curve (ROC)/area under the
      curve. In HIV-1-negative women, the percentage of cells that was positive for
      p16(INK4a) expression was significantly correlated with the severity of CIN (p <
      0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of
      89%, a specificity of 81%, a positive predictive value of 91% and a negative
      predictive value of 78%. HIV-seropositive women exhibited decreased expression of
      p16(INK4a) in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031).
      The ROC data underscore the potential utility of p16(INK4a) under defined
      conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical
      cancer. HIV-1 infection, however, is associated with relatively reduced
      p16(INK4a) expression in CIN 2-3.

PMID- 22850946
TI  - Comparative evaluation of the microplate nitrate reductase assay and the
      rezasurin microtitre assay for the rapid detection of multidrug resistant
      Mycobacterium tuberculosis clinical isolates.
AB  - The microplate nitrate reductase assay (MNRA) and the rezasurin microtitre assay
      (REMA) were used for the susceptibility testing of 73 clinical isolates and the
      results were compared with those that were obtained using the Bactec 460 TB and
      Bactec MGIT 960 systems. The REMA and the MNRA were performed in 96-well plates.
      For the REMA, the concentrations of isoniazid (INH) and rifampicin (RIF) ranged
      from 1.0-0.01 ug/mL and 2.0-0.03 ug/mL, respectively. For the MNRA, the INH
      concentration was between 1.0-0.03 ug/mL and the RIF concentration was between
      2.0-0.06 ug/mL. For the MNRA, the sensitivity, specificity, positive predictive
      value, negative predictive value and INH/RIF agreement were 100/95.6, 97.6/100,
      96.8/100, 100/98 and 98.6/98.6, respectively, and for the REMA, they were
      100/91.3, 90.4/100, 88.5/100, 100/96.1 and 94.5/97.2, respectively. Our data
      suggest that these two rapid, low-cost methods may be inexpensive, alternative
      assays for the rapid detection of multidrug resistant tuberculosis in low-income
      countries.

PMID- 22850947
TI  - Terbinafine inhibits Cryptococcus neoformans growth and modulates fungal
      morphology.
AB  - Cryptococcus neoformans is an encapsulated fungus that causes cryptococcosis.
      Central nervous system infection is the most common clinical presentation
      followed by pulmonary, skin and eye manifestations. Cryptococcosis is primarily
      treated with amphotericin B (AMB), fluconazole (FLC) and itraconazole (ITC). In
      the present work, we evaluated the in vitro effect of terbinafine (TRB), an
      antifungal not commonly used to treat cryptococcosis. We specifically examined
      the effects of TRB, either alone or in conjunction with AMB, FLC and ITC, on
      clinical C. neoformans isolates, including some isolates resistant to AMB and
      ITC. Broth microdilution assays showed that TRB was the most effective drug in
      vitro. Antifungal combinations demonstrated synergism of TRB with AMB, FLC and
      ITC. The drug concentrations used for the combination formulations were as much
      as 32 and 16-fold lower than the minimum inhibitory concentration (MIC) values of
      FLC and AMB alone, respectively. In addition, calcofluor white staining revealed
      the presence of true septa in hyphae structures that were generated after drug
      treatment. Ultrastructural analyses demonstrated several alterations in response
      to drug treatment, such as cell wall alterations, plasma membrane detachment,
      presence of several cytoplasmic vacuoles and mitochondrial swelling. Therefore,
      we believe that the use of TRB alone or in combination with AMB and azoles should
      be explored as an alternative treatment for cryptococcosis patients who do not
      respond to standard therapies.

PMID- 22850948
TI  - Simulium (Chirostilbia) brunnescens (Diptera: Simuliidae) - new species from the
      Brazilian cerrado, Manso Dam, state of Mato Grosso, Brazil.
AB  - A new species of Simuliidae, Simulium (Chirostilbia) brunnescens, was discovered
      at Chapada dos Guimaraes, state of Mato Grosso, Brazil, and nearby municipalities
      (Paranatinga, Rosario do Oeste and Nobres). This species is described here based
      on the adults, pupae and larvae. This species is closely related to Simulium (C.)
      subpallidum Lutz, but could be differentiated in all stages: females, leg colour
      pattern and frontal dilatation size; males, gonostyle shape; pupae, number of
      gill filaments; larvae, body size and colour, postgenal cleft, ratio between
      antenna and stalk of labral fan.

PMID- 22850949
TI  - The significance of the amoebocyte-producing organ in Biomphalaria glabrata.
AB  - In molluscs, internal defence against microorganisms is performed by a single
      cell type, i.e., the haemocyte or amoebocyte. The origin of these cells in
      Biomphalaria glabrata was initially thought to be localised within the vasculo
      connective tissue. More recently, origin from a single organ, termed the
      amoebocyte-producing organ (APO), has been postulated based on the occurrence of
      hyperplasia and mitoses during Schistosoma mansoni infection. The present
      investigation represents a histological, immuno-histochemical and ultra
      structural study of the B. glabrata APO, whereby histological identification was
      facilitated by means of collecting epithelial basophilic cells. These cells were
      comprised of single-cell layers that cover a portion of the stroma, which
      contains many small, round cells and haemolymph sinuses, as well as a small area
      of the pericardial surface of the reno-pericardial region. On occasion, this
      epithelial component vaguely resembled the vertebrate juxtaglomerular apparatus,
      which reinforces its presumed relationship to the kidney. Both in normal and
      infected molluscs, mitoses were only occasionally found. The present quantitative
      studies failed to demonstrate the presence of APO cellular hyperplasia, either in
      normal or schistosome-infected B. glabrata. Conversely, several structural
      details from the APO region in B. glabrata were found to be consistent with the
      hypothesis that the APO is a filtration organ, i.e., it is more closely related
      to the kidney rather than the bone marrow, as has been suggested in the
      literature.

PMID- 22850950
TI  - A palaeoparasitological analysis of rodent coprolites from the Cueva Huenul 1
      archaeological site in Patagonia (Argentina).
AB  - The aim of the present study was to examine the parasite fauna present in rodent
      coprolites collected from Cueva Huenul 1 (CH1), northern Neuquen (Patagonia,
      Argentina), an archaeological site that provides stratified sequences of
      archaeological and palaeontological remains dating from the Late
      Pleistocene/Early Holocene Transition to the Late Holocene period. Twenty rodent
      coprolites collected from different sedimentary units from the site, with ages
      ranging from 13.844 +/- 75-1.416 +/- 37 years BP, were examined for parasites.
      Each coprolite was processed as a whole: rehydrated, homogenised, spontaneously
      sedimented and examined using light microscopy. The coprolites and the eggs of
      any parasites present were described, measured and photographed. In all, 158
      parasite eggs were found in 10 coprolites. The faeces were positive for
      Viscachataenia quadrata Denegri, Dopchiz, Elissondo & Beveridge and Monoecocestus
      sp. Beddard (Cestoda: Anoplocephalidae) and for Heteroxynema (Cavioxyura)
      viscaciae Sutton & Hugot (Nematoda: Oxyuridae). The coprolites examined were
      tentatively attributed to Lagidium viscacia Molina (Mammalia, Rodentia,
      Caviomorpha, Chinchillidae). The life cycles of these parasites are discussed.

PMID- 22850951
TI  - Delimitation of kala-azar risk areas in the district of Vaishali in Bihar (India)
      using a geo-environmental approach.
AB  - Remote sensing and geographical information technologies were used to
      discriminate areas of high and low risk for contracting kala-azar or visceral
      leishmaniasis. Satellite data were digitally processed to generate maps of land
      cover and spectral indices, such as the normalised difference vegetation index
      and wetness index. To map estimated vector abundance and indoor climate data,
      local polynomial interpolations were used based on the weightage values.
      Attribute layers were prepared based on illiteracy and the unemployed proportion
      of the population and associated with village boundaries. Pearson's correlation
      coefficient was used to estimate the relationship between environmental variables
      and disease incidence across the study area. The cell values for each input
      raster in the analysis were assigned values from the evaluation scale. Simple
      weighting/ratings based on the degree of favourable conditions for kala-azar
      transmission were used for all the variables, leading to geo-environmental risk
      model. Variables such as, land use/land cover, vegetation conditions, surface
      dampness, the indoor climate, illiteracy rates and the size of the unemployed
      population were considered for inclusion in the geo-environmental kala-azar risk
      model. The risk model was stratified into areas of "risk"and "non-risk"for the
      disease, based on calculation of risk indices. The described approach constitutes
      a promising tool for microlevel kala-azar surveillance and aids in directing
      control efforts.

PMID- 22850952
TI  - Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the
      Brazilian Amazon Basin: to treat or not to treat?
AB  - In this study, we determined whether the treatment of asymptomatic parasites
      carriers (APCs), which are frequently found in the riverside localities of the
      Brazilian Amazon that are highly endemic for malaria, would decrease the local
      malaria incidence by decreasing the overall pool of parasites available to infect
      mosquitoes. In one village, the treatment of the 19 Plasmodium falciparum
      infected APCs identified among the 270 residents led to a clear reduction (Z = 
      2.39, p = 0.017) in the incidence of clinical cases, suggesting that treatment of
      APCs is useful for controlling falciparum malaria. For vivax malaria, 120 APCs
      were identified among the 716 residents living in five villages. Comparing the
      monthly incidence of vivax malaria in two villages where the APCs were treated
      with the incidence in two villages where APCs were not treated yielded
      contradictory results and no clear differences in the incidence were observed (Z
      = -0.09, p = 0.933). Interestingly, a follow-up study showed that the frequency
      of clinical relapse in both the treated and untreated APCs was similar to the
      frequency seen in patients treated for primary clinical infections, thus
      indicating that vivax clinical immunity in the population is not species specific
      but only strain specific.

PMID- 22850953
TI  - Persistence of experimental Rocio virus infection in the golden hamster
      (Mesocricetus auratus).
AB  - Rocio virus (ROCV) is an encephalitic flavivirus endemic to Brazil. Experimental
      flavivirus infections have previously demonstrated a persistent infection and, in
      this study, we investigated the persistence of ROCV infection in golden hamsters
      (Mesocricetus auratus). The hamsters were infected intraperitoneally with 9.8
      LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time
      points over a 120-day period to collect of blood, urine and organ samples. The
      viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR).
      The specimens were used to infect Vero cells and ROCV antigens in the cells were
      detected by immunefluorescence assay. The levels of antibodies were determined by
      the haemagglutination inhibition technique. A histopathological examination was
      performed on the tissues by staining with haematoxylin-eosin and detecting viral
      antigens by immunohistochemistry (IHC). ROCV induced a strong immune response and
      was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero
      cells exposed to samples from the viscera, brain, blood, serum and urine and was
      detected by qRT-PCR in the brain, liver and blood for three months after
      infection. ROCV induced histopathological changes and the expression of viral
      antigens, which were detected by IHC in the liver, kidney, lung and brain up to
      four months after infection. These findings show that ROCV is pathogenic to
      golden hamsters and has the capacity to cause persistent infection in animals
      after intraperitoneal infection.

PMID- 22850954
TI  - Validation of a modified fluorimetric assay for the screening of trichomonacidal
      drugs.
AB  - A fluorimetric microassay that uses a redox dye to determine the viability of the
      flagellate Trichomonas vaginalis has been optimised to provide a more sensitive
      method to evaluate potential trichomonacidal compounds. Resazurin has been used
      in recent years to test drugs against different parasites, including
      trichomonadid protozoa; however, the reproducibility of these resazurin-based
      methods in our laboratory has been limited because the flagellate culture medium
      spontaneously reduces the resazurin. The objective of this work was to refine the
      fluorimetric microassay method previously developed by other research groups to
      reduce the fluorescence background generated by the media and increase the
      sensitivity of the screening assay. The experimental conditions, time of
      incubation, resazurin concentration and media used in the microtitre plates were
      adjusted. Different drug sensitivity studies against T. vaginalis were developed
      using the 5-nitroimidazole reference drugs, new 5-nitroindazolinones and 5
      nitroindazole synthetic derivatives. Haemocytometer count results were compared
      with the resazurin assay using a 10% solution of 3 mM resazurin dissolved in
      phosphate buffered saline with glucose (1 mg/mL). The fluorimetric assay and the
      haemocytometer counts resulted in similar percentages of trichomonacidal activity
      in all the experiments, demonstrating that the fluorimetric microtitre assay has
      the necessary accuracy for high-throughput screening of new drugs against T.
      vaginalis.

PMID- 22850955
TI  - A combined approach of VNTR and MLST analysis: improving molecular typing of
      Argentinean isolates of Leptospira interrogans.
AB  - Leptospirosis is an emerging infectious disease that has been identified as both
      a human and animal health problem worldwide. Regular outbreaks associated with
      specific risk factors have been reported in Argentina. However, there are no
      available data concerning the genetic population level for this pathogen.
      Therefore, the aim of this work was to describe the genetic diversity of
      Leptospira interrogans through the application of two molecular typing
      strategies: variable number of tandem repeats (VNTR) and multilocus sequence
      typing (MLST). For this purpose, seven reference strains and 18 non
      epidemiologically related isolates from diverse hosts and Argentinean regions
      were analysed. Among them, nine genotypes and seven sequence types (STs),
      including three unreported STs, were described using VNTR and MLST, respectively.
      eBURST analysis demonstrated that ST37 was the most frequent and founder genotype
      of a clonal complex (CCs) containing STN1 and STN3, suggesting the importance of
      studying the serovars belonging to this CC in Argentina. The data from maximum
      parsimony analysis, which combined both techniques, achieved intra-serovar
      discrimination, surmounted microscopic agglutination test discrepancies and
      increased the discriminatory power of each technique applied separately. This
      study is the first to combine both strategies for L. interrogans typing to
      generate a more comprehensive molecular genotyping of isolates from Argentina in
      a global context.

PMID- 22850956
TI  - Declining prevalence of hepatitis A virus antibodies among children from low
      socioeconomic groups reinforces the need for the implementation of hepatitis A
      vaccination in Brazil.
AB  - Age-related seroprevalence studies that have been conducted in Brazil have
      indicated a transition from a high to a medium endemicity of hepatitis A virus
      (HAV) infection in the population. However, most of these studies have focused on
      urban populations that experience lower incidence rates of HAV infection. In the
      current study, the prevalence of anti-HAV antibodies was investigated in children
      with a low socioeconomic status (SES) that live on the periphery of three capital
      cities in Brazil. A total of 1,162 dried blood spot samples were collected from
      individuals whose ages ranged from one-18 years and tested for anti-HAV
      antibodies. A large number of children under five years old (74.1-90%) were
      identified to be susceptible to HAV infection. The anti-HAV antibody prevalence
      reached >= 50% among those that were 10-14 years of age or older. The anti-HAV
      prevalence rates observed were characteristics of regions with intermediate level
      of hepatitis A endemicity. These data indicated that a large proportion of
      children with a low SES that live at the periphery of urban cities might be at
      risk of contracting an HAV infection. The hepatitis A vaccine that is currently
      offered in Brazil is only available for high-risk groups or at private clinics
      and is unaffordable for individuals with a lower SES. The results from this study
      suggest that the hepatitis A vaccine should be included in the Brazilian National
      Program for Immunisation.

PMID- 22850957
TI  - The biology of three Mexican-American species of Triatominae (Hemiptera:
      Reduviidae): Triatoma recurva, Triatoma protracta and Triatoma rubida.
AB  - The values of biological parameters related to hatching, lifespan, the number of
      blood meals between moults, mortality, time lapse before the beginning of
      feeding, feeding time and defecation delay for each instar of three Mexican
      American species of Triatominae, Triatoma recurva, Triatoma protracta (former
      subspecies protracta) and Triatoma rubida (former subspecies uhleri), were
      evaluated and compared. No significant (p > 0.05) differences were recorded among
      the three species with respect to the average time required to hatch. This time
      was approximately 19 days. The average egg-to-adult development time was
      significantly (p < 0.05) shorter for T. rubida. The number of blood meals at each
      nymphal instar varied from one-five for each species. The mortality rates were
      higher for the first-instar nymphs of the three species studied. The mean time
      lapse before the beginning of feeding was between 0.3-3 min for most nymphs of
      all instars of each species studied. The mean feeding time was the longest for T.
      recurva, followed by T. protracta. The defecation delay was less than 10 min for
      T. recurva and T. rubida. Given these results, only T. rubida should be
      considered an important potential vector of Trypanosoma cruzi transmission to
      humans in areas of Mexico where these species exist, whereas T. recurva and T.
      protracta would be of secondary importance.

PMID- 22850958
TI  - Development and validation of PCR-based assays for diagnosis of American
      cutaneous leishmaniasis and identification of the parasite species.
AB  - In this study, PCR assays targeting different Leishmania heat-shock protein 70
      gene (hsp70) regions, producing fragments ranging in size from 230-390 bp were
      developed and evaluated to determine their potential as a tool for the specific
      molecular diagnosis of cutaneous leishmaniasis (CL). A total of 70 Leishmania
      strains were analysed, including seven reference strains (RS) and 63 previously
      typed strains. Analysis of the RS indicated a specific region of 234 bp in the
      hsp70 gene as a valid target that was highly sensitive for detection of
      Leishmania species DNA with capacity of distinguishing all analyzed species,
      after polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). This PCR assay was compared with other PCR targets used for the molecular
      diagnosis of leishmaniasis: hsp70 (1400-bp region), internal transcribed spacer
      (ITS)1 and glucose-6-phosphate dehydrogenase (G6pd). A good agreement among the
      methods was observed concerning the Leishmania species identification. Moreover,
      to evaluate the potential for molecular diagnosis, we compared the PCR targets
      hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue
      fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and
      PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using
      hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated
      with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis
      protocol.

PMID- 22850959
TI  - Toxicity of non-pyrethroid insecticides against Triatoma infestans (Hemiptera:
      Reduviidae).
AB  - Triatoma infestans (Klug) is the main vector of Chagas disease, which is a public
      health concern in most Latin American countries. The prevention of Chagas disease
      is based on the chemical control of the vector using pyrethroid insecticides. In
      the last decade, different levels of deltamethrin resistance have been detected
      in certain areas of Argentina and Bolivia. Because of this, alternative non
      pyrethroid insecticides from different chemical groups were evaluated against two
      T. infestans populations, NFS and El Mala, with the objective of finding new
      insecticides to control resistant insect populations. Toxicity to different
      insecticides was evaluated in a deltamethrin-susceptible and a deltamethrin
      resistant population. Topical application of the insecticides fenitrothion and
      imidacloprid to first nymphs had lethal effects on both populations, producing
      50% lethal dose (LD50) values that ranged from 5.2-28 ng/insect. However,
      amitraz, flubendiamide, ivermectin, indoxacarb and spinosad showed no
      insecticidal activity in first instars at the applied doses (LD50 > 200
      ng/insect). Fenitrothion and imidacloprid were effective against both
      deltamethrin-susceptible and deltamethrin-resistant populations of T. infestans.
      Therefore, they may be considered alternative non-pyrethroid insecticides for the
      control of Chagas disease.

PMID- 22850960
TI  - Hepatitis C virus quantification in serum and saliva of HCV-infected patients.
AB  - The hepatitis C virus (HCV) can be detected in blood and other bodily fluids,
      such as saliva, semen and gastric juices. The aim of this study was to compare
      the HCV viral loads in the serum and saliva of infected patients. Twenty-nine
      patients with detectable HCV RNA in their serum and saliva were included in this
      study. The HCV viral loads were determined through quantitative real-time
      polymerase chain reactions. The median viral RNA levels were 5.78 log10 copies in
      the serum and 3.32 log10 copies in the saliva. We observed that the salivary HCV
      viral load was significantly lower than the viral load in the serum. Further
      studies are required to understand the role of saliva in the diagnosis,
      management and potential transmission of HCV.

PMID- 22850961
TI  - The high prevalence of Torque teno virus DNA in blood donors and haemodialysis
      patients in southern Brazil.
AB  - This study investigates the frequency of Torque teno virus (TTV) infection in 150
      blood donors and 77 patients requiring haemodialysis in southern Brazil. Plasma
      samples were screened for TTV DNA using polymerase chain reaction (PCR). The
      prevalences of TTV among blood donors and patients requiring haemodialysis were
      73.3% and 68.8%, respectively. The presence of TTV was correlated with age in the
      blood donors (p = 0.024). In haemodialysis patients, no association was found
      between TTV infection and the demographic parameters (age, sex and education),
      the duration of haemodialysis or a history of blood transfusion. This study is
      the first to evaluate the prevalence of TTV infection in Brazilian patients
      requiring haemodialysis.

PMID- 22850962
TI  - The first report of the qnrB19, qnrS1 and aac(6')-Ib-cr genes in urinary isolates
      of ciprofloxacin-resistant Escherichia coli in Brazil.
AB  - In this study, we investigated the presence of plasmid-mediated quinolone
      resistance (PMQR) genes among 101 ciprofloxacin-resistant urinary Escherichia
      coli isolates and searched for mutations in the quinolone-resistance-determining
      regions (QRDRs) of the DNA gyrase and topoisomerase IV genes in PMQR-carrying
      isolates. Eight isolates harboured the qnr and aac(6')-Ib-cr genes (3 qnrS1, 1
      qnrB19 and 4 aac(6')-Ib-cr). A mutational analysis of the QRDRs in qnr and
      aac(6')-Ib-cr-positive isolates revealed mutations in gyrA, parC and parE that
      might be associated with high levels of resistance to quinolones. No mutation was
      detected in gyrB. Rare gyrA, parC and parE mutations were detected outside of the
      QRDRs. This is the first report of qnrB19, qnrS1 and aac(6')-Ib-cr -carrying E.
      coli isolates in Brazil.

PMID- 22850963
TI  - Comparison of the Kato-Katz and Helmintex methods for the diagnosis of
      schistosomiasis in a low-intensity transmission focus in Bandeirantes, Parana,
      southern Brazil.
AB  - The diagnosis of schistosomiasis is problematic in low-intensity transmission
      areas because parasitological methods lack sensitivity and molecular methods are
      neither widely available nor extensively validated. Helmintex is a method for
      isolating eggs from large faecal samples. We report preliminary results of a
      comparative evaluation of the Helmintex and Kato-Katz (KK) methods for the
      diagnosis of schistosomiasis in a low-intensity transmission area in
      Bandeirantes, Parana, southern Brazil. Eggs were detected by both methods in
      seven patients, whereas only Helmintex yielded positive results in four
      individuals. The results confirm the previously demonstrated higher sensitivity
      of the Helmintex method compared with the KK method.

PMID- 22850964
TI  - Infections with human coronaviruses NL63 and OC43 among hospitalised and
      outpatient individuals in Sao Paulo, Brazil.
AB  - The incidence and clinical features of human coronaviruses (HCoVs) among
      Brazilian patients with respiratory illness are not well known. We investigated
      the prevalence of HCoVs among Brazilian outpatients and hospitalised patients
      with respiratory illnesses during 2009 and 2010. To identify the HCoVs,
      pancoronavirus and species-specific reverse-transcriptase polymerase chain
      reaction assays were performed. Five of 394 samples were positive for HCoVs
      (1.2%): 1/182 (0.5%) outpatients and 4/212 (1.8%) hospitalised patients. The OC43
      and NL63 HCoVs were identified. Two patients were admitted to the intensive care
      unit. Underlying chronic disease was reported in cases and one diabetic adult
      died. HCoVs can cause lower respiratory infections and hospitalisation. Patients
      with pre-existing conditions and respiratory infections should be evaluated for
      HCoV infections.

PMID- 22850965
TI  - Coxiella burnetii, the agent of Q fever in Brazil: its hidden role in
      seronegative arthritis and the importance of molecular diagnosis based on the
      repetitive element IS1111 associated with the transposase gene.
AB  - Coxiella burnetii is the agent of Q fever , an emergent worldwide zoonosis of
      wide clinical spectrum. Although C. burnetii infection is typically associated
      with acute infection, atypical pneumonia and flu-like symptoms, endocarditis,
      osteoarticular manifestations and severe disease are possible, especially when
      the patient has a suppressed immune system; however, these severe complications
      are typically neglected. This study reports the sequencing of the repetitive
      element IS1111 of the transposase gene of C. burnetii from blood and
      bronchoalveolar lavage (BAL) samples from a patient with severe pneumonia
      following methotrexate therapy, resulting in the molecular diagnosis of Q fever
      in a patient who had been diagnosed with active seronegative polyarthritis two
      years earlier. To the best of our knowledge, this represents the first documented
      case of the isolation of C. burnetii DNA from a BAL sample.

PMID- 22850966
TI  - A RT-PCR method for selective amplification and phenotypic characterization of
      all three serotypes of Sabin-related polioviruses from viral mixtures.
AB  - Outbreaks caused by vaccine-derived polioviruses are challenging the final
      eradication of paralytic poliomyelitis. Therefore, the surveillance of the acute
      flaccid paralysis cases based on poliovirus isolation and characterization
      remains an essential activity. Due to the use of trivalent oral poliovirus
      vaccine (OPV), mixtures containing more than one serotype of Sabin-related
      polioviruses are frequently isolated from clinical samples. Because each
      poliovirus isolate needs to be individually analyzed, we designed polymerase
      chain reaction primers that can selectively distinguish and amplify a genomic
      segment of the three Sabin-related poliovirus serotypes present in mixtures,
      thus, optimizing the diagnosis and providing prompt information to support
      epidemiologic actions.

PMID- 22850967
TI  - The use of an adequate mathematical model is crucial to evaluate vaccine
      effectiveness.

PMID- 22850968
TI  - Synthesis and antitumor activity of alpha-aminophosphonates containing
      thiazole[5,4-b]pyridine moiety.
AB  - A new procedure is developed for the synthesis of alpha-aminophosphonates
      containing thiazole[5,4-b]pyridine moiety from conveniently available starting
      materials. The target compounds were characterized by infrared, (1)H NMR, (13)C
      NMR, (31)P NMR, mass spectrometry and elemental analysis. The newly synthesized
      compounds were evaluated for their anticancer activities against PC-3, Bcap-37,
      H460 cells in vitro by the MTT method. Compounds 3b and 3f are highly effective
      against PC-3, Bcap-37 cells and good to H460 cells. Further study is necessary to
      find out the potential antitumor activities.

PMID- 22850969
TI  - Huge coronary fistula from the left anterior descending coronary artery to the
      right ventricle in a newborn: a rare congenital anomaly.
AB  - We present a case of a neonate with a huge congenital fistula from the left
      anterior descending coronary artery to the right ventricle and additional heart
      defects. The circumflex coronary artery was supplied by the right coronary
      artery. The fistula was closed surgically at both ends.

PMID- 22850970
TI  - Cor triatiratum dexter: a rare cause of isolated right atrial enlargement.
AB  - Cor triatriatum sinistrum (division of the left atrium) is a recognized clinical
      and surgical entity. Division of the right atrium, also known as cor triatriatum
      dexter, is an extremely rare congenital abnormality in which persistence of the
      right valve of the embryonic systemic sinus venosus divides the right atrium into
      two chambers. Typically, the right atrial partition is due to exaggerated fetal
      eustachian and thebesian valves, which together form an incomplete septum across
      the lower part of the atrium. This septum may range from a reticulum to a
      substantial sheet of tissue. Cor triatriatum dexter can be diagnosed at any age,
      especially if it is incidentally discovered. Usually, this anomaly is recorded at
      necropsy. This report describes the case of a divided right atrium evaluated for
      nonspecific symptoms and unexplained cardiomegaly with right atrial enlargement.

PMID- 22850972
TI  - Belief and affect: on the mental pre-cursors of health-related cognition and
      behaviour.
AB  - This paper will discuss the importance of concepts such as belief and affect to
      the theory and practice of health psychology, and the potential contribution of
      the revised conceptualisation of belief proposed in the target article will be
      considered. In the first half of the paper a number of important differences
      between the new approach and established empirical approaches to the study of
      beliefs will be highlighted. The second half of the paper will focus on the
      important relationship between affect and beliefs, one of the key issues
      addressed in the target paper. A number of recent theories linking affect and
      belief will be reviewed, and recent empirical research demonstrating the
      psychological mechanisms linking affect and belief will be discussed. In light of
      the considerable achievements of this line of inquiry, it is concluded that the
      proposed new approach and definition of belief does not as yet offer a preferable
      alternative to understanding the role of belief in health-related cognition and
      behaviour.

PMID- 22850971
TI  - Cardiac mass with calcification forming pulmonary atresia in utero; a case of
      fetal endocarditis.
AB  - Fetal intracardiac mass with calcification is very rare and not well reported.
      The authors treated a patient with a cardiac mass presumed to be infective
      endocarditis in the tricuspid valve and pulmonary valve positions with
      postcalcification echocardiographic shadow forming pulmonary atresia. Although
      postnatal consecutive blood cultures for bacterial and fungal pathogens tested
      negative, serial follow-up echocardiograms and surgical findings suggested
      infective endocarditis. This report describes a very rare case of presumed fetal
      infective endocarditis presenting as a calcified mass, which was successfully
      treated by partial resection without significant morbidity. 

PMID- 22850973
TI  - Qualitative findings in a long-term disordered eating prevention programme follow
      up with school-going girls.
AB  - The assessment of eating disorder prevention-programmes has mainly been addressed
      quantitatively excluding complexity that may improve prevention. We compared
      perceptions of eating, female and male aesthetic-models, media influences,
      prevention-programmes and emerging topics among 12 young females who received a
      media literacy programme (N = 4), media literacy plus nutrition awareness
      programme (N = 4) or were assigned to a control condition (N = 4). Interpretative
      Phenomenological Analysis highlighted ego-syntonic eating-patterns and signs of
      internalization of the thin ideal. Findings provide invaluable and rich
      information to improve future iterations of the programme.

PMID- 22850974
TI  - Belief, emotion, and health: toward an integrative account. Commentary on John
      Cromby's 'beyond belief'.
AB  - This commentary identifies in Cromby's formulation of belief the potentials for
      developing three innovative approaches to belief systems: emotion as meaning,
      cognition as dialogue, and an aesthetic model of meaning making based on Susanne
      Langer's integrative approach to feeling and form. It is argued that the
      semiotics of Charles Sanders Peirce can help to weave these threads into an
      integrative theory to shed some light on the connection between belief, emotion,
      and health.

PMID- 22850975
TI  - Skin explant cultures as a source of keratinocytes for cultivation.
AB  - Cultivated human keratinocytes can be used successfully in the treatment of burn
      patients, but efforts to heal burns and other wounds can be hampered by the very
      small skin biopsies available for cultivation of transplantable keratinocyte
      sheets. A small biopsy (and correspondingly small number of enzymatically
      isolated keratinocytes for use in classical cultivation techniques) can lead to a
      low yield of multilayer sheets for clinical application or unacceptably long
      cultivation times. One way of addressing this is to make use of skin remnants
      remaining after enzymatic digestion and culture cells migrating out of these skin
      explants. Sufficient numbers of explant-derived keratinocytes can be obtained to
      facilitate additional routine cultivation of these cells. Biopsy remnants can be
      used to initiate explant cultures repeatedly (we were able to re-use pieces of
      skin 10 times and still obtain useful numbers of keratinocytes) and this
      "passaging" yields substantially more cells for classical cultivation than would
      be available from conventional methodology alone, and in a comparable timeframe.
      Another advantage of this method is that it does not require additional biopsies
      to be procured from already-compromised patients and overcomes problems
      associated with contamination of skin samples with resistant hospital-acquired
      bacterial infections common during prolonged hospitalization.

PMID- 22850976
TI  - Phenolic constituents of the Chilean herbal tea Fabiana imbricata R. et P.
AB  - "Pichi" or "pichi romero" (Fabiana imbricata R. et. P., Solanaceae) is a Chilean
      plant used as a tea in the Andean regions of Chile and Argentina. A very simple
      and direct method was developed for the qualitative analysis of polyphenols in
      the tea by high-performance liquid chromatography (HPLC) with diode array
      detection and electrospray ionization tandem mass spectrometry. The phenolic
      constituents identified in the teas were chlorogenic acid (3-O-caffeoylquinic
      acid), p-hydroxyacetophenone, scopoletin and quercetin derivatives. The
      glycosides were mainly glucosides from p-hydroxyacetophenone and scopoletin while
      di- and tri-glycosides from quercetin were the main flavonoids. The content of
      the main phenolic compounds in the teas (g/100 g lyophilized infusion) was 0.8
      1.9 % for scopoletin, 0.4-6.2 % for p-hydroxyacetophenone and 2.1-4.3 % for
      rutin, respectively. The health-promoting properties reported for this herbal tea
      can be associated with the presence of several phenolics with known antioxidant,
      diuretic and antiinflammatory activity.

PMID- 22850977
TI  - Changing indications for penetrating keratoplasty in Homburg/Saar from 2001 to
      2010--histopathology of 1,200 corneal buttons.
AB  - BACKGROUND: To evaluate the trends in indications for penetrating keratoplasty
      (PKP) in Homburg/Saar between 2001 and 2010. METHODS: Retrospective review of
      1,200 corneal buttons which underwent PKP that were performed between 2001 and
      2010 at the Department of Ophthalmology of Saarland University Hospital, Germany.
      Indications were classified into eight different groups following histological
      analysis: keratoconus, Fuchs' dystrophy, bullous keratopathy, corneal scars,
      keratitis, regraft, corneal dystrophy other than Fuchs' dystrophy, and other
      diagnoses. Two different time periods (between 2001-2005 and between 2006-2010)
      were analyzed. RESULTS: Keratoconus (25.5 %) was the most common indication for
      PKP in our study, followed by Fuchs' dystrophy (21.2 %), bullous keratopathy
      (14.6 %), corneal scars (14.4 %), keratitis (13.0 %), regraft (7.0 %), non-Fuchs'
      dystrophies (2.1 %), and other diagnoses (2.3 %). Comparing the two different
      time periods, a trend of significantly increasing frequency of keratoconus and
      Fuchs' dystrophy, and a decreasing frequency of corneal scars, were found as
      indications for PKP in our study. CONCLUSIONS: Keratoconus was the leading
      indication for PKP in our series, and had a significantly increasing trend from
      2001-2005 to 2006-2010. The percentage of patients with Fuchs' dystrophy
      increased, and became the second most common indication for PKP, while the number
      of PKPs for corneal scars decreased during the last 5 years in our institution.

PMID- 22850978
TI  - Local delivery of alendronate eluting chitosan scaffold can effectively increase
      osteoblast functions and inhibit osteoclast differentiation.
AB  - The aim of this study was to investigate the effect of alendronate released from
      chitosan scaffolds on enhancement of osteoblast functions and inhibition of
      osteoclast differentiation in vitro. The surface and cell morphologies of
      chitosan scaffolds and alendronate-loaded chitosan scaffolds were characterized
      by variable pressure field emission scanning electron microscope (VP-FE-SEM).
      Alendronate was released in a sustained manner. For evaluating osteoblast
      functions in MG-63 cells, we investigated cell proliferation, alkaline
      phosphatase (ALP) activity, and calcium deposition. Furthermore, for evaluating
      inhibition of osteoclast differentiation in RAW 264.7 cells, we investigated
      tartrate-resistant acid phosphatase (TRAP) activity, TRAP staining, and gene
      expressions. The in vitro studies revealed that osteoblasts grown on alendronate
      loaded chitosan scaffold showed a significant increment in cell proliferation,
      ALP activity, and calcium deposition as compared to those grown on chitosan
      scaffolds. In addition, the in vitro study showed that osteoclast differentiation
      in RAW 264.7 cells cultured on alendronate-loaded chitosan scaffolds was greatly
      inhibited as compared to those cultured on chitosan scaffolds by the results of
      TRAP activity, TRAP staining, and gene expressions. Taken together, alendronate
      loaded chitosan scaffolds could achieve the dual functions of improvement in
      osteoblast functions and inhibition of osteoclast differentiation. Thus,
      alendronate-eluting chitosan substrates are promising materials for enhancing
      osteoblast functions and inhibiting osteoclast differentiation in orthopedic and
      dental fields.

PMID- 22850979
TI  - Regulation of atherosclerosis and associated risk factors by adenosine and
      adenosine receptors.
AB  - Adenosine is an endogenous metabolite that has an anti-inflammatory effect across
      the vasculature. Extracellular adenosine activates 4 G-protein coupled receptors
      (A1, A3, A2A, and A2B) whose expression varies in different cells and tissues,
      including the vasculature and blood cells. Higher levels of adenosine are
      generated during stress, inflammation, and upon tissue damage. Some of the
      adenosine receptors (AR), such as the A2BAR, are further up-regulated following
      such stresses. This review discusses the role of adenosine and adenosine
      receptors in the development of atherosclerosis and some of the risk factors
      associated with this pathology. These include adenosine receptor-regulated
      changes in atherosclerosis, blood pressure, thrombosis, and myocardial
      infarction. Potential therapeutic applications are reviewed, as well as reasons
      for phenotypic differences occasionally observed between receptor knockout and
      pharmacological inhibition via drug administration.

PMID- 22850981
TI  - Novel polyoxometalate hybrids consisting of copper-lanthanide
      heterometallic/lanthanide germanotungstate fragments.
AB  - Three organic-inorganic hybrid copper-lanthanide heterometallic
      germanotungstates, {[Cu(en)(2)(H(2)O)] [Cu(3)Eu(en)(3)(OH)(3)(H(2)O)(2)](alpha
      GeW(11)O(39))}(2).11H(2)O (1),
      {[Cu(en)(2)(H(2)O)][Cu(3)Tb(en)(3)(OH)(3)(H(2)O)(2)](alpha
      GeW(11)O(39))}(2).11H(2)O (2) and
      {[Cu(en)(2)(H(2)O)][Cu(3)Dy(en)(3)(OH)(3)(H(2)O)(2)](alpha
      GeW(11)O(39))}(2).10H(2)O (3) and three polyoxometalate hybrids built by
      lanthanide-containing germanotungstates and copper-ethylendiamine complexes,
      Na(2)H(6)[Cu(en)(2)(H(2)O)](8){Cu(en)(2)[La(alpha-GeW(11)O(39))(2)](2)}.18H(2)O
      (4),
      K(4)H(2)[Cu(en)(2)(H(2)O)(2)](5)[Cu(en)(2)(H(2)O)](2)[Cu(en)(2)](2){Cu(en)(2)[Pr(
      lpha-GeW(11)O(39))(2)](2)}.16H(2)O (5) and
      KNa(2)H(7)[enH(2)](3)[Cu(en)(2)(H(2)O)](2)[Cu(en)(2)](2){Cu(en)(2)[Er(alpha
      GeW(11)O(39))(2)](2)}.15H(2)O (6) (en = ethylenediamine) have been hydrothermally
      synthesized and structurally characterized by elemental analyses, inductively
      coupled plasma atomic emission spectrometry (ICP-AES) analyses, IR spectra,
      powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS) and
      single-crystal X-ray diffraction. 1-3 are essentially isomorphous and their main
      skeletons display the interesting dimeric motif
      {[Cu(3)Ln(en)(3)(OH)(3)(H(2)O)(2)](alpha-GeW(11)O(39))}(2)(4-), which is
      constructed from two {Cu(3)LnO(4)} cubane anchored monovacant [alpha
      GeW(11)O(39)](8-) fragments through two W-O-Ln-O-W linkers. The primary backbones
      of 4-6 exhibit the tetrameric architecture {Cu(en)(2)[Ln(alpha
      GeW(11)O(39))(2)](2)}(24-) built by two 1:2-type [Ln(alpha-GeW(11)O(39))(2)](13-)
      moieties and one [Cu(en)(2)](2+) bridge, albeit they are not isostructural. To
      our knowledge, 1-6 are rare polyoxometalate derivatives consisting of copper
      lanthanide heterometallic/lanthanide germanotungstate fragments. 1 exhibits
      antiferromagnetic coupling interactions within the {Cu(3)EuO(4)} cubane units,
      while 2 and 3 display dominant ferromagnetic interactions between the
      Tb(III)/Dy(III) and Cu(II) cations. The room-temperature solid-state
      photoluminescence properties of 1-3 have been investigated.

PMID- 22850980
TI  - Kruppel-like factors and vascular inflammation: implications for atherosclerosis.

PMID- 22850982
TI  - Oral atypical cellular blue nevus: an infiltrative melanocytic proliferation.
AB  - The atypical cellular blue nevus is an extremely rare nevomelanocytic lesion
      which lacks precise histologic characterization in the current literature. Given
      the potential for significant architectural and cytologic overlap with melanoma,
      further study, including molecular analysis, is needed. This is the first
      description of an atypical cellular blue nevus of the oral cavity.

PMID- 22850983
TI  - Acantholytic squamous cell carcinoma in upper aerodigestive tract:
      histopathology, immunohistochemical profile and epithelial mesenchymal transition
      phenotype change.
AB  - Acantholytic squamous cell carcinoma is a rare variant of squamous cell carcinoma
      in the mucosa of upper aerodigestive tract. Histomorphologically, acantholytic
      squamous cell carcinoma may lose the typical features of conventional squamous
      cell carcinoma and mimic other epithelial or mesenchymal malignancies due to
      advanced acantholysis and dyskeratosis. Because of its rarity, information of
      prognosis, pathologic features and immunohistochemical profiles is limited. We
      have studied clinicopathologic features and immunohistochemical profiles of four
      acantholytic squamous cell carcinoma cases arising from upper aerodigestive
      tract. Clinical results indicate an aggressive biologic behavior.
      Morphologically, all tumors revealed significant acantholysis with separation of
      tumor cells and intratumoral spaces. The tumor cells were highly pleomorphic and
      growth patterns were variable. In immunohistochemical studies, all tumor cells
      revealed positive reactions for AE1/AE3 and p63 supporting a squamous epithelial
      origin. In contrast to conventional aerodigestive squamous cell carcinoma,
      acantholytic squamous cell carcinoma showed significant reductions of
      cytokeratin19, E-cadherin and concomitant up-regulation of vimentin expression.
      Both morphologic features and immunohistochemical profiles indicate that
      acantholytic squamous cell carcinoma has acquired an epithelial mesenchymal
      transition phenotype. However, in contrast to other solid malignant tumors, the
      epithelial mesenchymal transition phenotype change in acantholytic squamous cell
      carcinoma is not limited to the invasive front of the peripheral tumor but,
      rather, diffusely involves entire neoplastic lesion. In addition, because
      cytokeratin 19 staining is attenuated, this would be an insensitive marker for
      following up and/or in detecting disseminated tumor cells in cases of
      acantholytic squamous cell carcinoma in upper aerodigestive tract.

PMID- 22850984
TI  - Synthesis of methyl ketones by metabolically engineered Escherichia coli.
AB  - Methyl ketones are a group of highly reduced platform chemicals with widespread
      applications in the fragrance, flavor and pharmacological industries. Current
      methods for the industrial production of methyl ketones include oxidation of
      hydrocarbons, but recent advances in the characterization of methyl ketone
      synthases from wild tomato have sparked interest towards the development of
      microbial platforms for the industrial production of methyl ketones. A functional
      methyl ketone biosynthetic pathway was constructed in Escherichia coli by over
      expressing two genes from Solanum habrochaites: shmks2, encoding a 3-ketoacyl-ACP
      thioesterase, and shmks1, encoding a beta-decarboxylase. These enzymes enabled
      methyl ketone synthesis from 3-ketoacyl-ACP, an intermediate in the fatty acid
      biosynthetic cycle. The production of 2-nonanone, 2-undecanone, and 2-tridecanone
      by MG1655 pTH-shmks2-shmks1 was initially detected by nuclear magnetic resonance
      and gas chromatography-mass spectrometry analyses at levels close to 6 mg/L. The
      deletion of major fermentative pathways leading to ethanol (adhE), lactate
      (ldhA), and acetate (pta, poxB) production allowed for the carbon flux to be
      redirected towards methyl ketone production, doubling total methyl ketone
      concentration. Variations in methyl ketone production observed under different
      working volumes in flask experiments led to a more detailed analysis of the
      effects of oxygen availability on methyl ketone concentration in order to
      determine optimal levels of oxygen. The methyl ketone concentration achieved with
      MG1655 ?adhE ?ldhA ?poxB ?pta pTrcHis2A-shmks2-shmks1, the best performer strain
      in this study, was approximately 500 mg/L, the highest reported for an engineered
      microorganism. Through the establishment of optimal operating conditions and by
      executing rational metabolic engineering strategies, we were able to increase
      methyl ketone concentrations by almost 75-fold from the initial confirmatory
      levels.

PMID- 22850985
TI  - Internal plug mesh without fixation in laparoscopic total extraperitoneal (TEP)
      repair of inguinal hernias: a pilot study.
AB  - PURPOSE: Mesh fixation is essential in laparoscopic total extraperitoneal (TEP)
      repair of inguinal hernia; however, fixation sometimes causes post-operative
      pain. This study investigated a novel method of laparoscopic TEP repair without
      mesh fixation. METHODS: This study reviewed data from about two-hundred and forty
      one laparoscopic TEP repairs on 219 patients, which were performed between
      December 2004 and October 2005. RESULTS: There were no statistically significant
      differences in the recurrence rate, seroma formation, and hospital stay. However,
      the mean operation time was shorter in the internal plug mesh group than the
      fixation group (p = 0.009), and post-operative pain only occurred in 4 cases in
      the internal plug mesh group in comparison to 29 cases in the mesh fixation group
      (p = 0.014). CONCLUSIONS: An internal plug mesh without fixation might reduce
      post-operative pain after laparoscopic TEP repair of an inguinal hernia. Internal
      plug mesh without fixation may be an alternative method in laparoscopic TEP
      repair, especially for those involving indirect hernias.

PMID- 22850986
TI  - Tissue engineering - nanomaterials in the musculoskeletal system.
AB  - The musculoskeletal tissues bone, cartilage and ligament/tendon are highly
      structured nanocomposites consisting of nanofibres embedded in a matrix of
      different composition. Thus, it was a logical step that during the hype of nano
      in the last decade, nanotechnology and nanomaterials became a hot topic in the
      field of musculoskeletal repair. Especially the fact that using nanomaterials
      would encompass a biomimetic approach, thus copying nature, was promising.
      However, it became evident that using nanomaterials in the repair of
      musculoskeletal tissues had a longer history than initially thought and its way
      was paved with failures, which are important to remember when applying current
      ideas. This current opinion paper summarises some fundamental aspects of
      nanomaterials to be used for musculoskeletal application and discusses where this
      field might move to in the near future.

PMID- 22850988
TI  - Impact of dams and irrigation schemes in Anopheline (Diptera: Culicidae)
      bionomics and malaria epidemiology.
AB  - Irrigation schemes and dams have posed a great concern on public health systems
      of several countries, mainly in the tropics. The focus of the present review is
      to elucidate the different ways how these human interventions may have an effect
      on population dynamics of anopheline mosquitoes and hence, how local malaria
      transmission patterns may be changed. We discuss different studies within the
      three main tropical and sub-tropical regions (namely Africa, Asia and the Pacific
      and the Americas). Factors such as pre-human impact malaria epidemiological
      patterns, control measures, demographic movements, human behaviour and local
      Anopheles bionomics would determine if the implementation of an irrigation scheme
      or a dam will have negative effects on human health. Some examples of successful
      implementation of control measures in such settings are presented. The use of
      Geographic Information System as a powerful tool to assist on the study and
      control of malaria in these scenarios is also highlighted.

PMID- 22850989
TI  - Antibody levels to hantavirus in inhabitants of western Santa Catarina State,
      Brazil.
AB  - Hantavirus cardiopulmonary syndrome (HCPS) is an infectious disease caused by
      hantaviruses of the family Bunyaviridae, and is transmitted by aerosols of
      excreta of infected rodents. The aim of the present study was to determine
      antibody levels to hantavirus in the population that lives at frontier of Brazil
      and Argentina. Participated of the study 405 individuals living in the
      municipalities of Bandeirante, Santa Helena, Princesa and Tunapolis, state of
      Santa Catarina, Brazil. IgG antibodies to hantavirus were analyzed in sera by an
      ELISA that uses a recombinant N protein of Araraquara hantavirus as antigen. The
      results were also confirmed by immunofluorescent test. Eight individuals showed
      antibodies to hantavirus (1.97% positivity), with serum titers ranging from 100
      to 800. Six seropositives were males, older than 30 years and farmers. Our
      results reinforce previous data on hantavirus circulation and human infections in
      the southern border of Brazil with Argentina.

PMID- 22850990
TI  - In vitro synergism of simvastatin and fluconazole against Candida species.
AB  - Systemic fungal infections are responsible for high mortality rates. Several
      species of fungi may be involved, but Candida spp. is the most prevalent.
      Simvastatin is used to lower cholesterol and also exhibits antifungal action. The
      aim of this study was to evaluate the synergistic action of simvastatin with
      fluconazole against strains of Candida spp. Susceptibility testing was performed
      according to protocol M27-A3, by broth microdilution method and the synergistic
      effect of simvastatin and fluconazole was calculated based on FICI (Fractional
      Inhibitory Concentration Index). Eleven strains were evaluated, and simvastatin
      showed a synergistic effect with fluconazole against 10 (91%) of the Candida spp.
      strains tested. Simvastatin may be a valuable drug in the treatment of systemic
      infections caused by Candida spp.

PMID- 22850991
TI  - High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the
      urine of HIV-infected patients without neurological symptoms in Sao Paulo,
      Brazil.
AB  - OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in
      HIV-infected patients without neurological symptoms. METHODS: Urine samples from
      HIV-infected patients without neurological symptoms were tested for JC virus and
      BK virus by PCR. Samples were screened for the presence of polyomavirus with sets
      of primers complementary to the early region of JCV and BKV genome (AgT). The
      presence of JC virus or BK virus were confirmed by two other PCR assays using
      sets of primers complementary to the VP1 gene of each virus. Analysis of the data
      was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates
      for categorical variables. RESULTS: A total of 75 patients were included in the
      study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75
      (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV
      DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in
      42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion
      of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results
      differ from the others available on the literature.

PMID- 22850993
TI  - "Quo vadis, life on earth".

PMID- 22850992
TI  - Genetic diversity and primary resistance among HIV-1-positive patients from
      Maringa, Parana, Brazil.
AB  - The objective of this study is to identify subtypes of Human Immunodeficiency
      Virus type 1 (HIV-1) and to analyze the presence of mutations associated to
      antiretroviral resistance in the protease (PR) and reverse transcriptase (RT)
      regions from 48 HIV-1 positive treatment naive patients from an outpatient clinic
      in Maringa, Parana, Brazil. Sequencing was conducted using PR, partial RT and
      group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA.
      Transmitted resistance was determined according to the Surveillance Drug
      Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of
      concatenated genetic segments classified sequences as subtype B 19/48 (39.6%),
      subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant
      forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F
      (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance
      were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary
      data may subsidize the monitoring of the HIV evolution in the region.

PMID- 22850994
TI  - Seventeen years of American cutaneous leishmaniasis in a Southern Brazilian
      municipality.
AB  - We reviewed the records of 151 patients diagnosed with American cutaneous
      leishmaniasis (ACL) from 1993 to 2009 in the municipality of Japura, Parana,
      Brazil. Gender, age, occupation, place of residence, location of lesions, type
      and number of lesions were analyzed. The prevalence rate of ACL was 11.5/10,000
      hab, of which 84.7% were male, 58.3% lived in rural area and 49.0% were farmers.
      The most frequent age group was between 30 to 39 years (26.6%). Skin lesions
      occurred in 92.7% of the patients with predominance in the lower limbs (23.9%)
      and 49.1% of the records did not include the number of lesions location due to
      incomplete filling. A single ulceration was present in 44.4%. Japura is an
      endemic area for ACL, requiring public actions and preventive education.

PMID- 22850995
TI  - Scientific authorships and collaboration network analysis on Chagas disease:
      papers indexed in PubMed (1940-2009).
AB  - Chagas disease is a chronic, tropical, parasitic disease, endemic throughout
      Latin America. The large-scale migration of populations has increased the
      geographic distribution of the disease and cases have been observed in many other
      countries around the world. To strengthen the critical mass of knowledge
      generated in different countries, it is essential to promote cooperative and
      translational research initiatives. We analyzed authorship of scientific
      documents on Chagas disease indexed in the Medline database from 1940 to 2009.
      Bibliometrics was used to analyze the evolution of collaboration patterns. A
      Social Network Analysis was carried out to identify the main research groups in
      the area by applying clustering methods. We then analyzed 13,989 papers produced
      by 21,350 authors. Collaboration among authors dramatically increased over the
      study period, reaching an average of 6.2 authors per paper in the last five-year
      period. Applying a threshold of collaboration of five or more papers signed in co
      authorship, we identified 148 consolidated research groups made up of 1,750
      authors. The Chagas disease network identified constitutes a "small world,"
      characterized by a high degree of clustering and a notably high number of
      Brazilian researchers.

PMID- 22850996
TI  - Optochiasmatic tuberculoma as the sole manifestation of late recurrent
      tuberculosis.
AB  - Brain tuberculomas account for 10-20% of space occupying brain lesions in
      developing countries. Most lesions are observed at time of tuberculosis diagnosis
      or soon after starting treatment. We herein describe a 32 year-old patient with a
      14-month history of headache and progressive visual loss. Her past medical
      history revealed pulmonary tuberculosis treated eight years before. A brain MRI
      showed a T1- and T2-weighted isointense contrast-enhancing lesion in the optic
      chiasm. A presumptive diagnosis of optochiasmatic tuberculoma was made and
      isoniazid, rifampin, pyrazinamide, and ethambutol were started. Despite
      treatment, the patient evolved to blindness. The prompt recognition of this
      condition is extremely important since the presence of optochiasmal enhancement
      is associated with blindness in patients with tuberculosis.

PMID- 22850997
TI  - Acute gouty arthritis as a manifestation of immune reconstitution inflammatory
      syndrome after initiation of antiretroviral therapy.
AB  - Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects
      initiating antiretroviral therapy most commonly involves new or worsening
      manifestations of previously subclinical or overt infectious diseases. Reports of
      non-infectious IRIS are much less common but represent important diagnostic and
      treatment challenges. We report on a 34-year-old HIV-infected male patient with
      no history of gout who developed acute gouty arthritis in a single joint one
      month after initiating highly active antiretroviral therapy.

PMID- 22850998
TI  - Analogies in medicine: anchovy paste in the liver.

PMID- 22850999
TI  - Trypanosoma cruzi: the supposed removal of the use of the xenodiagnosis and blood
      culture.

PMID- 22851000
TI  - Universal varicella vaccination needs to be high on the agenda in China.

PMID- 22851001
TI  - Dynamic ABCG2 expression in human embryonic stem cells provides the basis for
      stress response.
AB  - ABCG2 is a plasma membrane multidrug transporter with an established role in the
      cancer drug-resistance phenotype. This protein is expressed in a variety of
      tissues, including several types of stem cell. Although ABCG2 is not essential
      for life, knock-out mice were found to be hypersensitive to xenobiotics and had
      reduced levels of the side population of hematopoietic stem cells. Previously we
      have shown that ABCG2 is present in human embryonic stem cell (hESC) lines, with
      a heterogeneous expression pattern. In this study we examined this heterogeneity,
      and investigated whether it is related to stress responses in hESCs. We did not
      find any difference between expression of pluripotency markers in ABCG2-positive
      and negative hESCs; however, ABCG2-expressing cells had a higher growth rate
      after cell separation. We found that some harmful conditions (physical stress,
      drugs, and UV light exposure) are tolerated much better in the presence of ABCG2
      protein. This property can be explained by the transporter function which
      eliminates potential toxic metabolites accumulated during stress conditions. In
      contrast, mild oxidative stress in hESCs caused rapid internalization of ABCG2,
      indicating that some environmental factors may induce removal of this transporter
      from the plasma membrane. On the basis of these results we suggest that a dynamic
      balance of ABCG2 expression at the population level has the advantage of enabling
      prompt response to changes in the cellular environment. Such actively maintained
      heterogeneity might be of evolutionary benefit in protecting special cell types,
      including pluripotent stem cells.

PMID- 22851002
TI  - The role of G-domain orientation and nucleotide state on the Ras isoform-specific
      membrane interaction.
AB  - Ras proteins are proto-oncogenes that function as molecular switches linking
      extracellular stimuli with an overlapping but distinctive range of biological
      outcomes. Although modulatable interactions between the membrane and the Ras C
      terminal hypervariable region (HVR) harbouring the membrane anchor motifs enable
      signalling specificity to be determined by their location, it is becoming clear
      that the spatial orientation of different Ras proteins is also crucial for their
      functions. To reveal the orientation of the G-domain at membranes, we conducted
      an extensive study on different Ras isoforms anchored to model raft membranes.
      The results show that the G-domain mediates the Ras-membrane interaction by
      inducing different sets of preferred orientations in the active and inactive
      states with largely parallel orientation relative to the membrane of most of the
      helices. The distinct locations of the different isoforms, exposing them to
      different effectors and regulators, coupled with different G-domain-membrane
      orientation, suggests synergy between this type of recognition motif and the
      specificity conferred by the HVR, thereby validating the concept of isoform
      specificity in Ras.

PMID- 22851003
TI  - Score equivalence of electronic and paper versions of the Social Difficulties
      Inventory (SDI-21): a randomised crossover trial in cancer patients.
AB  - PURPOSE: The Social Difficulties Inventory (SDI-21) assesses everyday problems
      experienced by cancer patients, including difficulties with self-care, work and
      relationships. Early development and psychometric evaluation studies have
      validated the SDI-21 for computer administration. However, several recent studies
      have administered the SDI-21 on paper. We sought to test the score equivalence of
      electronic and paper versions of the SDI-21. METHODS: A randomised two-arm
      crossover trial in a sample of cancer patients with varied diagnoses. Patients
      completed electronic (via the internet) and paper versions of the SDI-21, with
      half randomly assigned to complete the electronic version first (n = 51) and half
      the paper version first (n = 60). Patients were asked to complete both versions
      at home, within 2 weeks. Analyses were performed for the SDI-21 summary score and
      three subscales. RESULTS: Score distributions and internal reliabilities for the
      paper and electronic versions were highly similar. There were no significant
      differences between mean summary or subscale scores for the two administration
      modes. All mean score differences (all <0.25 of a scale point) were well below
      the SDI-21's established minimally important differences, and all 95 % confidence
      intervals were narrow and included zero. Intraclass correlations between paper
      and electronic scores were uniformly high and significant (all >=0.85) and above
      the standard acceptable level of reliability. CONCLUSIONS: Paper and electronic
      versions of the SDI-21 can be considered equivalent and used interchangeably.
      This is important because, despite the growth of electronic formats, paper
      versions are currently still necessary to ensure inclusive use of the SDI-21 with
      representative samples.

PMID- 22851004
TI  - Inhibition of metastatic tumor formation in vivo by a bacteriophage display
      derived galectin-3 targeting peptide.
AB  - Galectin-3 (gal-3) is involved in the metastatic cascade and interacts with the
      cancer-associated carbohydrate, Thomsen-Freidenreich (TF) antigen during early
      stages of metastatic adhesion and tumor formation. Our laboratory previously
      utilized bacteriophage display to select a peptide, G3-C12, with high specificity
      and affinity for gal-3 that was able to inhibit cancer cell adhesion. We
      hypothesized that G3-C12 would inhibit TF/gal-3 and gal-3/gal-3 interactions in
      vitro and in vivo and would moderate early steps of the metastatic cascade
      leading to reduced carcinogenesis in vivo. To test this, adhesion of multiple
      breast carcinoma cell lines to purified gal-3 and a TF-mimic was measured in the
      presence/absence of G3-C12 resulting in an average reduction of cellular adhesion
      by 50 and 59 %, respectively. Sensitive optical imaging experiments were utilized
      to monitor the fate of intravenously injected MDA-MB-231 human breast carcinoma
      cells expressing luciferase into athymic nude mice in the presence/absence of G3
      C12 in vivo. Intravenous administration of G3-C12 reduced lung colonization of
      MDA-MB-231-luciferase cells within mice by 72 % when compared to saline, whereas,
      control peptide treatments resulted in no significant reduction of colonization.
      Histologic examination of excised lung tissue, at day 70, revealed that mice
      treated with G3-C12 possessed 4.63 +/- 3.07 tumors compared to 14.13 +/- 3.56
      tumors within mice treated with saline. Also, within both saline and control
      peptide treatment groups, 37 % of mouse lungs contained tumor thrombi, compared
      to 0 % within the G3-C12 treatment group. This study demonstrated that G3-C12
      significantly reduced metastatic cell deposition and consequent outgrowth within
      vasculature of mice.

PMID- 22851005
TI  - Lymphatics, lymph nodes and the immune system: barriers and gateways for cancer
      spread.
AB  - Metastasis to the regional lymph node is the most important prognostic indicator
      for the outcomes of patients with sold cancer. In general, it is well recognized
      that cancer development is genetically determined with progression from the
      microenvironment of the primary tumor site, oftentimes via the SLN gateway, to
      the distant sites. In about 20 % of the time, the cancer cells may spread
      directly through the blood vascular system to the distant sites. Thus, in
      general, cancer progression is consistent with Hellman's spectrum theory in that
      development of nodal and systemic metastasis from a localized cancer growth is a
      progressive process. Cancer proliferation within the tumor microenvironment may
      give rise to increased tumor heterogeneity, which is further complicated by its
      continuous change through its evolution within the host in a Darwinian sense. It
      is crucial to understand the molecular process of lymphangiogenesis and
      hemangiogenesis in the tumor microenvironment with respect to the initial steps
      of cancer cells entering into the lymphatic and vascular systems so that rational
      therapy can be developed to curb the process of specific routes of metastasis.
      This chapter elucidates the role of lymphatics, nodal metastasis and antitumor
      immunity. We present novel immune targets in nodal metastases, the importance of
      the lymph node as a pre-metastatic niche, and immune-related proteins as
      biomarkers of metastasis.

PMID- 22851006
TI  - Immune aspects of sepsis and hope for new therapeutics.
AB  - Marked alterations of the innate and adaptive immune response follow invasive
      infection and generalized inflammatory states. If left unchecked, this state of
      immune dysregulation contributes to a myriad of maladaptive cellular responses
      that culminate in multiple organ dysfunction, septic shock, and lethality. The
      molecular details of the cell-signaling networks that underlie the
      pathophysiology of systemic inflammation and sepsis are now increasingly well
      understood. While a vigorous and effective immune response to invasive pathogens
      is essential for microbial clearance and host survival, nonresolving, generalized
      inflammation can induce diffuse endovascular damage, increased capillary
      permeability, coagulopathy, and widespread tissue damage. Current evidence
      indicates that a state of relative immune suppression often accompanies sepsis
      and might provide novel therapeutic options in some patients. An expanding number
      of potential therapeutic options are now in clinical development to reestablish
      control and promote resolution over sepsis-induced systemic inflammation and
      organ dysfunction.

PMID- 22851007
TI  - Inhibition of the intracellular Ca(2+) transporter SERCA (Sarco-Endoplasmic
      Reticulum Ca(2+)-ATPase) by the natural polyphenol epigallocatechin-3-gallate.
AB  - The use of a microsomal preparation from skeletal muscle revealed that both
      Ca(2+) transport and Ca(2+)-dependent ATP hydrolysis linked to Sarco-Endoplasmic
      Reticulum Ca(2+)-ATPase are inhibited by epigallocatechin-3-gallate (EGCG). A
      half-maximal effect was achieved at approx. 12 MUM. The presence of the galloyl
      group was essential for the inhibitory effect of the catechin. The relative
      inhibition of the Ca(2+)-ATPase activity decreased when the Ca(2+) concentration
      was raised but not when the ATP concentration was elevated. Data on the catalytic
      cycle indicated inhibition of maximal Ca(2+) binding and a decrease in Ca(2+)
      binding affinity when measured in the absence of ATP. Moreover, the addition of
      ATP to samples in the presence of EGCG and Ca(2+) led to an early increase in
      phosphoenzyme followed by a time-dependent decay that was faster when the drug
      concentration was raised. However, phosphorylation following the addition of ATP
      plus Ca(2+) led to a slow rate of phosphoenzyme accumulation that was also
      dependent on EGCG concentration. The results are consistent with retention of the
      transporter conformation in the Ca(2+)-free state, thus impeding Ca(2+) binding
      and therefore the subsequent steps when ATP is added to trigger the Ca(2+)
      transport process. Furthermore, phosphorylation by inorganic phosphate in the
      absence of Ca(2+) was partially inhibited by EGCG, suggesting alteration of the
      native Ca(2+)-free conformation at the catalytic site.

PMID- 22851008
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is a subclinical myopathy, usually triggered by
      volatile anaesthetics and depolarising muscle relaxants. Clinical symptoms are
      variable, and the condition is sometimes difficult to identify. Nevertheless,
      rapid recognition and specific as well as symptomatic treatment are crucial to
      avoid a lethal outcome. Molecular genetic investigations have confirmed the
      skeletal muscle type ryanodine receptor to be the major MH locus with more than
      70% of MH families carrying a mutation in this gene. There is no screening method
      to test for MH, as current tests are invasive (open muscle biopsy) or restricted
      to MH families with known MH-associated mutations (molecular genetic testing).
      The prevalence of the MH trait is unknown, because the clinical penetrance after
      contact with triggering agents is very variable. More recently, MH mutations have
      been associated with rhabdomyolysis following statin therapy or with non
      pharmacological triggering, such as exertional heat stroke.

PMID- 22851009
TI  - Recombinant HCMV UL128 expression and functional identification of PBMC
      attracting activity in vitro.
AB  - Human cytomegalovirus (HCMV) has evolved several immune evasion strategies. One
      strategy is controlling the movement of peripheral blood mononuclear cells
      (PBMCs) by encoding homologues of chemokines. Our aim was to determine whether
      HCMV open reading frame (ORF) UL128 could encode a protein that attracts PBMCs
      like a beta-chemokine. The recombinant UL128 protein was synthesized by
      construction of a stably transfected CHO-UL128 cell line, and a chemotaxis assay
      showed that UL128 was able to attract PBMCs with a potency equal to that of MIP
      1alpha in vitro. We hypothesize that UL128 protein may act as a beta-chemokine
      homologue in viral pathogenesis.

PMID- 22851010
TI  - Isolation of two Chinese bovine enteroviruses and sequence analysis of their
      complete genomes.
AB  - In this study, RNA corresponding to bovine enterovirus (BEV) was detected in 24.6
      % of faecal samples (17/69) from diarrheic and healthy cattle in six different
      areas in China by an RT-PCR screening method. Furthermore, two cytopathic agents,
      designated as BHM26 and BJ50, were isolated from the bovine diarrheic fecal
      samples. During passage in MA104 cells, ultrathin sections of virus-infected
      monolayers were examined using a transmission electron microscope, and a large
      number of symmetrical virus crystals were seen in the cytoplasm, with monomorphic
      small viral particles of 27-30 nm in diameter. The full-length RNA genomes were
      7433 and 7416 nucleotides long, respectively, with a genome organization
      analogous to that of picornaviruses. Phylogenetic analysis of the VP1 and VP3
      capsid protein coding sequences suggested that the viruses BHM26 and BJ50 belong
      to genotype 2 of the BEV cluster B (BEV-B). In addition, sequence comparisons of
      the 5' and 3' UTRs and P1, P2 and P3 subgenomic regions of the two isolates
      suggested that there were intergenotypic recombination events occurring during
      evolution of the BHM26 and BJ50 isolates.

PMID- 22851012
TI  - Erratum to: Femoroacetabular impingement: a review of diagnosis and management.

PMID- 22851011
TI  - Gaze orientation interferes with mental numerical representation.
AB  - Number comparison tasks are characterized by distance and size effects. The
      distance effect reveals that the higher the distance is between two numbers, the
      easier their magnitude comparison is. Accordingly, people are thought to
      represent numbers on a spatial dimension, the mental number line, on which any
      given number corresponds to a location on the line. The size effect, instead,
      states that at any given distance, comparing two small numbers is easier than
      comparing two large numbers, thus suggesting that larger numbers are more vaguely
      represented than smaller ones. In the present work we first tested whether the
      participants were adopting a spatial strategy to solve a very simple numbers
      comparison task, by assessing the presence of the distance and the magnitude
      effect. Secondarily, we focused on the influence of gaze position on their
      performance. The present results provide evidence that gaze direction interferes
      with number comparisons, worsening the vague representation of larger numbers and
      further supporting the hypothesis of the overlapping between physical and mental
      spaces.

PMID- 22851013
TI  - Controlling autonomous underwater floating platforms using bacterial
      fermentation.
AB  - Biogenic gas has a wide range of energy applications from being used as a source
      for crude bio-oil components to direct ignition for heating. The current study
      describes the use of biogenic gases from Clostridium acetobutylicum for a new
      application-renewable ballast regeneration for autonomous underwater devices.
      Uninterrupted (continuous) and blocked flow (pressurization) experiments were
      performed to determine the overall biogas composition and total volume generated
      from a semirigid gelatinous matrix. For stopped flow experiments, C.
      acetobutylicum generated a maximum pressure of 55 psi over 48 h composed of 60 %
      hydrogen gas when inoculated in a 5 % agar (w/v) support with 5 % glucose (w/v)
      in the matrix. Typical pressures over 24 h at 318 K ranged from 10 to 33 psi.
      These blocked flow experiments show for the first time the use of microbial gas
      production as a way to repressurize gas cylinders. Continuous flow experiments
      successfully demonstrated how to deliver biogas to an open ballast control
      configuration for deployable underwater platforms. This study is a starting point
      for engineering and microbiology investigations of biogas which will advance the
      integration of biology within autonomous systems.

PMID- 22851014
TI  - Implementation of a transhydrogenase-like shunt to counter redox imbalance during
      xylose fermentation in Saccharomyces cerevisiae.
AB  - Three enzymes responsible for the transhydrogenase-like shunt, including malic
      enzyme (encoded by MAE1), malate dehydrogenase (MDH2), and pyruvate carboxylase
      (PYC2), were overexpressed to regulate the redox state in xylose-fermenting
      recombinant Saccharomyces cerevisiae. The YPH499XU/MAE1 strain was constructed by
      overexpressing native Mae1p in the YPH499XU strain expressing xylose reductase
      and xylitol dehydrogenase from Scheffersomyces stipitis, and native xylulokinase.
      Analysis of the xylose fermentation profile under semi-anaerobic conditions
      revealed that the ethanol yield in the YPH499XU/MAE1 strain (0.38 +/- 0.01 g g-1
      xylose consumed) was improved from that of the control strain (0.31 +/- 0.01 g g
      1 xylose consumed). Reduced xylitol production was also observed in
      YPH499XU/MAE1, suggesting that the redox balance was altered by Mae1p
      overexpression. Analysis of intracellular metabolites showed that the redox
      imbalance during xylose fermentation was partly relieved in the transformant. The
      specific ethanol production rate in the YPH499XU/MAE1-MDH2 strain was 1.25-fold
      higher than that of YPH499XU/MAE1 due to the additional overexpression of Mdh2p,
      whereas the ethanol yield was identical to that of YPH499XU/MAE1. The specific
      xylose consumption rate was drastically increased in the YPH499XU/MAE1-MDH2-PYC2
      strain. However, poor ethanol yield as well as increased production of xylitol
      was observed. These results demonstrate that the transhydrogenase function
      implemented in S. cerevisiae can regulate the redox state of yeast cells.

PMID- 22851015
TI  - Comparative characterization of recombinant ZZ protein-alkaline phosphatase and
      its application in enzyme immunoassays.
AB  - A functional fusion protein, which consists of an antibody and an enzyme that can
      be used in enzyme immunoassays, has been constructed. However, a quantitative
      comparison of the characteristics of fusion proteins and chemical conjugates of
      the parents, which are functionally produced in a uniform microbial system, has
      not been adequately achieved. In this study, a fusion protein between the ZZ
      protein and Escherichia coli alkaline phosphatase (AP) and the parental ZZ
      protein and AP for chemical conjugate was functionally produced in the same
      bacterial system. A detailed examination of the ZZ-AP fusion protein and the
      effect of the ZZ-AP chemical conjugate on IgG affinity and enzymatic activity
      were performed. Compared with the parents, the equilibrium dissociation constant
      of ZZ-AP conjugate decreased by 32 % and catalytic activity decreased by 24 %,
      whereas the ZZ-AP fusion retained full parental activities and exhibited an
      approximately tenfold higher sensitivity than that of ZZ-AP conjugate in enzyme
      linked immunosorbent assay. Thus, ZZ-AP fusion is a promising immunoreagent for
      IgG detection and a potential biolinker between antibodies and reporter enzymes
      (i.e., IgG-ZZ-AP fusion complex) in immunoassays.

PMID- 22851016
TI  - A novel transcriptional regulator, ClbR, controls the cellobiose- and cellulose
      responsive induction of cellulase and xylanase genes regulated by two distinct
      signaling pathways in Aspergillus aculeatus.
AB  - The cellobiose- and cellulose-responsive induction of the FIII-avicelase (cbhI),
      FII-carboxymethyl cellulase (cmc2), and FIa-xylanase (xynIa) genes is not
      regulated by XlnR in Aspergillus aculeatus, which suggests that this fungus
      possesses an unknown cellulase gene-activating pathway. To identify the
      regulatory factors involved in this pathway, we constructed a random insertional
      mutagenesis library using Agrobacterium tumefaciens-mediated transformation of A.
      aculeatus NCP2, which harbors a transcriptional fusion between the cbhI promoter
      (P ( CBHI )) and the orotidine 5'-phosphate decarboxylase gene (pyrG). Of the
      ~6,000 transformants screened, one 5-FOA-resistant transformant, S4-22, grew
      poorly on cellulose-containing media and exhibited reduced cellobiose-induced
      expression of cbhI. Southern blot analysis and nucleotide sequencing of the
      flanking regions of the T-DNA inserted in S4-22 indicated that the T-DNA was
      inserted within the coding region of a previously unreported Zn(II)(2)Cys(6)
      transcription factor, which we designated the cellobiose response regulator
      (ClbR). The disruption of the clbR gene resulted in a significant reduction in
      the expression of cbhI and cmc2 in response to cellobiose and cellulose.
      Interestingly, the cellulose-responsive induction of FI-carboxymethyl cellulase
      (cmc1) and FIb-xylanase (xynIb) genes that are under the control of XlnR, was
      also reduced in the clbR-deficient mutant, but there was no effect on the
      induction of these genes in response to D-xylose or L-arabinose. These data
      demonstrate that ClbR participates in both XlnR-dependent and XlnR-independent
      cellobiose- and cellulose-responsive induction signaling pathways in A.
      aculeatus.

PMID- 22851017
TI  - Priority pollutant degradation by the facultative methanotroph, Methylocystis
      strain SB2.
AB  - Methylocystis strain SB2, a facultative methanotroph capable of growth on multi
      carbon compounds, was screened for its ability to degrade the priority pollutants
      1,2-dichloroethane (1,2-DCA), 1,1,2-trichloroethane (1,1,2-TCA), and 1,1
      dichloroethylene (1,1-DCE), as well as cis-dichloroethylene (cis-DCE) when grown
      on methane or ethanol. Methylocystis strain SB2 degraded 1,2-DCA and 1,1,2-TCA
      when grown on either substrate and cis-DCE when grown on methane. Growth of
      Methylocystis strain SB2 on methane was inhibited in the presence of all
      compounds, while only 1,1-DCE and cis-DCE inhibited growth on ethanol. No
      degradation of any chlorinated hydrocarbon was observed in ethanol-grown cultures
      when particulate methane monooxygenase (pMMO) activity was inhibited with the
      addition of acetylene, indicating that competition for binding to the pMMO
      between the chlorinated hydrocarbons and methane limited both methanotrophic
      growth and pollutant degradation when this strain was grown on methane.
      Characterization of Methylocystis strain SB2 found no evidence of a high-affinity
      form of pMMO for methane, nor could this strain utilize 1,2-DCA or its putative
      oxidative products 2-chloroethanol or chloroactetic acid as sole growth
      substrates, suggesting that this strain lacks appropriate dehydrogenases for the
      conversion of 1,2-DCA to glyoxylate. As ethanol: (1) can be used as an
      alternative growth substrate for promoting pollutant degradation by Methylocystis
      strain SB2 as the pMMO is not required for its growth on ethanol and (2) has been
      used to enhance the mobility of chlorinated hydrocarbons in situ, it is proposed
      that ethanol can be used to enhance both pollutant transport and biodegradation
      by Methylocystis strain SB2.

PMID- 22851019
TI  - TeX4 (X = F, Cl, Br) as Lewis acids--complexes with soft thio- and seleno-ether
      ligands.
AB  - TeF(4) reacts with OPR(3) (R = Me or Ph) in anhydrous CH(2)Cl(2) to give the
      colourless, square based pyramidal 1 : 1 complexes [TeF(4)(OPR(3))] only, in
      which the OPR(3) is coordinated basally in the solid state, (R = Me: d(Te-O) =
      2.122(2) A; R = Ph: d(Te-O) = 2.1849(14) A). Variable temperature (19)F{(1)H},
      (31)P{(1)H} and (125)Te{(1)H} NMR spectroscopic studies strongly suggest this is
      the low temperature structure in solution, although the systems are dynamic. The
      much softer donor ligands SMe(2) and SeMe(2) show a lower affinity for TeF(4),
      although unstable, yellow products with spectroscopic features consistent with
      [TeF(4)(EMe(2))] are obtained by the reaction of TeF(4) in neat SMe(2) or via
      reaction in CH(2)Cl(2) with SeMe(2). TeX(4) (X = F, Cl or Br) causes oxidation
      and halogenation of TeMe(2) to form X(2)TeMe(2). The Br(2)TeMe(2) hydrolyses in
      trace moisture to form [BrMe(2)Te-O-TeMe(2)Br], the crystal structure of which
      has been determined. TeX(4) (X = Cl or Br) react with the selenoethers SeMe(2),
      MeSe(CH(2))(3)SeMe or o-C(6)H(4)(SeMe)(2) (X = Cl) in anhydrous CH(2)Cl(2) to
      give the distorted octahedral monomers trans-[TeX(4)(SeMe(2))(2)], cis
      [TeX(4){MeSe(CH(2))(3)SeMe}] and cis-[TeCl(4){o-C(6)H(4)(SeMe)(2)}], which have
      been characterised by IR, Raman and multinuclear NMR ((1)H, (77)Se{(1)H} and
      (125)Te{(1)H}) spectroscopy, and via X-ray structure determinations of
      representative examples. Tetrahydrothiophene (tht) can form both 1 : 1 and 1 : 2
      Te : L complexes. For X = Br, the former has been shown to be a Br-bridged dimer,
      [Br(3)(tht)Te(MU-Br)(2)TeBr(3)(tht)], by crystallography with the tht ligands
      anti, whereas the latter are trans-octahedral monomers. Like its selenoether
      analogue, MeS(CH(2))(3)SMe forms distorted octahedral cis-chelates,
      [TeX(4){MeS(CH(2))(3)SMe}], whereas the more rigid o-C(6)H(4)(SMe)(2)
      unexpectedly forms a zig-zag chain polymer in the solid state, [TeCl(4){o
      C(6)H(4)(SMe)(2)}](n), in which the dithioether adopts an extremely unusual
      bridging mode. This is in contrast to the chelating monomer, cis-[TeCl(4){o
      C(6)H(4)(SeMe)(2)}], formed with the analogous selenoether and may be attributed
      to small differences in the ligand chelate bite angles. The wider bite angle
      xylyl-linked bidentates, o-C(6)H(4)(CH(2)EMe(2))(2) behave differently; the
      thioether forms cis-chelated [TeX(4){o-C(6)H(4)(CH(2)SMe)(2)}] confirmed
      crystallographically, whereas the selenoether undergoes C-Se cleavage and
      rearrangement on treatment with TeX(4), forming the cyclic selenonium salts,
      [C(9)H(11)Se](2)[TeX(6)]. The tetrathiamacrocycle, [14]aneS(4) (1,4,8,11
      tetrathiacyclotetradecane), does not react cleanly with TeCl(4), but forms the
      very poorly soluble [TeCl(4)([14]aneS(4))](n), shown by crystallography to be a
      zig-zag polymer with exo-coordinated [14]aneS(4) units linked via alternate S
      atoms to a cis-TeCl(4) unit. Trends in the (125)Te{(1)H} NMR shifts for this
      series of Te(IV) halides chalcogenoether complexes are discussed.

PMID- 22851020
TI  - Which educational programs promote the success of international medical graduates
      in psychiatry training?

PMID- 22851018
TI  - Reductive whole-cell biotransformation with Corynebacterium glutamicum:
      improvement of NADPH generation from glucose by a cyclized pentose phosphate
      pathway using pfkA and gapA deletion mutants.
AB  - In this study, the potential of Corynebacterium glutamicum for reductive whole
      cell biotransformation is shown. The NADPH-dependent reduction of the prochiral
      methyl acetoacetate (MAA) to the chiral (R)-methyl 3-hydroxybutyrate (MHB) by an
      alcohol dehydrogenase from Lactobacillus brevis (Lbadh) was used as model
      reaction and glucose served as substrate for the regeneration of NADPH. Since
      NADPH is mainly formed in the oxidative branch of the pentose phosphate pathway
      (PPP), C. glutamicum was engineered to redirect carbon flux towards the PPP.
      Mutants lacking the genes for 6-phosphofructokinase (pfkA) or glyceraldehyde 3
      phosphate dehydrogenase (gapA) were constructed and analyzed with respect to
      growth, enzyme activities, and biotransformation performance. Both mutants showed
      strong growth defects in glucose minimal medium. For biotransformation of MAA to
      MHB using glucose as reductant, strains were transformed with an Lbadh expression
      plasmid. The wild type showed a specific MHB production rate of 3.1 mmol(MHB) h(
      1) g (cdw) (-1) and a yield of 2.7 mol(MHB) mol (glucose) (-1) . The ?pfkA mutant
      showed a similar MHB production rate, but reached a yield of 4.8 mol(MHB) mol
      (glucose) (-1) , approaching the maximal value of 6 mol(NADPH) mol (glucose) (-1)
      expected for a partially cyclized PPP. The specific biotransformation rate of the
      DeltagapA mutant was decreased by 62 % compared to the other strains, but the
      yield was increased to 7.9 mol(MHB) mol (glucose) (-1) , which to our knowledge
      is the highest one reported so far for this mode of NADPH regeneration. As one
      fourth of the glucose was converted to glycerol, the experimental yield was close
      to the theoretically maximal yield of 9 mol(NADPH) mol (glucose) (-1) .

PMID- 22851021
TI  - Acculturation, education, training, and workforce issues of IMGs: current status
      and future directions.

PMID- 22851022
TI  - Psychodynamic psychotherapy training as acculturative experience for
      international medical graduates: a commentary.

PMID- 22851023
TI  - Preparing international medical graduates for psychiatry residency: a multi-site
      needs assessment.
AB  - OBJECTIVE: Despite the growing number of international medical graduates (IMGs)
      training in medicine in Canada and the United States, IMG-specific challenges
      early in psychiatry residency have not been fully explored. Therefore, the
      authors conducted a needs-assessment survey to determine the needs of IMGs
      transitioning into psychiatry residency. METHOD: Using a 15-item online
      questionnaire, authors conducted a needs-assessment of IMG residents in five
      Canadian psychiatry residency programs. The survey examined IMGs' perceived
      difficulties with the transition into psychiatry residency, educational needs,
      and demographic data. Data were analyzed with descriptive statistics and Mann
      Whitney tests. RESULTS: IMGs identified the following difficulties with their
      transition into residency: understanding the healthcare system, medical
      documentation, and evidence-based medicine/mental health. Language barriers and
      social isolation were significant factors affecting the transition into residency
      for residents who did not speak English as their first language. Residents who
      lived in Canada 12 months or less had greater perceived difficulties in
      psychotherapy knowledge and adapting to the Canadian healthcare system; 88% of
      IMGs reported having little-or-no IMG-specific preparation for psychiatry
      residency from their psychiatry program; however, 69% reported that they would
      use IMG resources if offered; 63% felt that faculty in their program should
      undergo training to assist with IMG transition. CONCLUSION: Several perceived
      challenges, needs, and gaps in training were reported by IMGs in Canadian
      psychiatry residency programs. The results of this survey will be used to inform
      future curriculum development to facilitate IMG transition into psychiatry
      postgraduate training programs.

PMID- 22851024
TI  - Helping international medical graduates engage in effective feedback.
AB  - OBJECTIVE: Timely, specific, behaviorally-based feedback is a cornerstone of
      medical education. The authors review basic tenets of effective feedback delivery
      in the context of potential challenges faced by (non-United States) international
      medical graduates (IMGs). METHOD: The authors provide a brief summary of the
      elements of effective feedback, with illustrations of potential barriers for
      IMGs. RESULTS: Many IMGs were trained in a hierarchical system, where feedback
      was delivered publicly, in a manner associated with shame and embarrassment.
      These experiences, combined with the challenge of functioning in a second
      language and anxieties over exposing weaknesses, present some barriers that make
      it more difficult for them to participate in feedback inquiry, self-reflection,
      and reciprocal feedback. CONCLUSIONS: These challenges can be mitigated by
      acknowledging the anxieties that learners may have, fostering a learning culture
      that values feedback as an expected and important part of all learning, ensuring
      that all (learners and supervisors) are trained in feedback skills, and clear
      setting of expectations.

PMID- 22851026
TI  - Psychotherapy training for IMGs: attending to the "how to" and "what to" teach.
AB  - International Medical Graduates (IMGs) make up a significant portion of the
      United States and Canadian workforce, and are well represented in psychiatry
      residency training programs. A review of the literature indicates that before
      entering residency training, many IMGs have minimal exposure to the behavioral
      sciences and poor communication skills-training; significant issues for learning
      psychotherapy. Given the lack of clear direction in the literature, this article
      presents empirically-informed guidelines relevant to the training of
      International Medical Graduates in psychotherapy.

PMID- 22851027
TI  - The role of international medical graduate psychiatrists in the United States
      healthcare system.
AB  - OBJECTIVE: International medical graduates (IMGs) make up a substantial
      proportion of the United States physician workforce, including psychiatrists in
      practice. The purpose of this study was to describe, based on current data, the
      characteristics and qualities of IMG psychiatrists who provide patient care in
      the US. METHOD: Physician data from the Educational Commission for Foreign
      Medical Graduates, American Medical Association, and American Board of Medical
      Specialties were combined. Descriptive statistics provided an overview of the
      characteristics and qualities of IMG psychiatrists. The authors contrasted
      demographic and practice profiles of IMG and U.S. medical graduate (USMG)
      psychiatrists. RESULTS: International medical graduates make up almost one-third
      of the practicing psychiatrist workforce. Nearly one-quarter of these individuals
      attended medical school in India. Compared with USMG psychiatrists, IMG
      psychiatrists were more likely to be employed in a hospital and less likely to be
      Board-certified by the American Board of Psychiatry and Neurology. CONCLUSIONS:
      International medical graduate psychiatrists play an important role in the U.S.
      healthcare system. Given their numbers and their propensity to practice in
      settings and areas where USMGs do not, efforts to monitor their practice patterns
      and qualities, both cross-sectionally and longitudinally, are warranted.

PMID- 22851028
TI  - A roadmap for observership programs in psychiatry for international medical
      graduates.
AB  - OBJECTIVE: International medical graduates (IMGs) constitute a significant
      proportion of the psychiatric workforce in the United States. Observership
      programs serve an important role in preparing IMGs for U.S. residency positions;
      yet there are limited resources with information available on establishing these
      observerships, and none specific to psychiatry. In this article, authors present
      a roadmap for observership programs in psychiatry for IMGs. METHOD: This article
      draws on the experience of the IMG committee of the Group for Advancement of
      Psychiatry in establishing observership programs. RESULTS: Authors highlight the
      benefits of observership programs to IMGs, psychiatry departments, and the U.S.
      medical system as a whole. The different components of an observership program
      are presented, along with core competencies that need to be acquired. The authors
      discuss challenges that observership programs may encounter as well as
      recommendations for overcoming them. CONCLUSION: Observership programs provide a
      unique opportunity to integrate IMGs into the U.S. medical system. This article
      provides a framework for establishing such programs in a way that will optimize
      their benefits and avoid potential pitfalls.

PMID- 22851029
TI  - Systems-based aspects in the training of IMG or previously trained residents:
      comparison of psychiatry residency training in the United States, Canada, the
      United Kingdom, India, and Nigeria.
AB  - OBJECTIVES: International medical graduates (IMGs) account for a significant
      proportion of residents in psychiatric training in the United States. Many IMGs
      may have previously completed psychiatry residency training in other countries.
      Their experiences may improve our system. Authors compared and contrasted
      psychiatry residency training in the U.S. to that of Canada, the United Kingdom,
      India, and Nigeria. The study also highlights the systems-based features that may
      have an impact on the adaptation of IMGs (especially previously-trained) to U.S.
      psychiatry residency. METHODS: Individuals who are familiar with psychiatry
      residency training in the United States and were previously trained in other
      countries synthesized information available on websites, official documents, and
      previous literature, as well as their experiences with past training. RESULTS:
      Psychiatry residencies vary considerably in all five countries in terms of the
      duration of training, curriculum, clinical experience, psychotherapy training,
      research experience, supervision, and evaluation processes. Residency training in
      the U.S., Canada, and the U.K. is well-structured and has more psychotherapy
      training. The U.K. has enhanced exposure to community psychiatry. The U.K.,
      India, and Nigeria have increased emphasis on psychopathology. Training in India
      and Nigeria has a higher quantity of clinical work, less record-keeping, less
      emphasis on patient autonomy, and a mandatory prospective clinical research
      requirement. CONCLUSIONS: The provision of services and training is substantially
      influenced by national mental health policies, culture, and local traditions.
      Despite numerous commonalities, there are some differences in psychiatry training
      among all five countries. Awareness of these differences in education, systems,
      and interactions may help psychiatric educators to understand IMGs (especially
      those previously-trained) as they adapt to U.S. training.

PMID- 22851030
TI  - Psychiatric residents' attitudes toward and experiences with the clinical-skills
      verification process: a pilot study on U.S. and international medical graduates.
AB  - OBJECTIVE: The authors report on a pilot study of the experiences and perceptions
      of foreign international medical graduate (F-IMG), United States international
      medical graduate (US-IMG), and United States medical graduate (USMG) psychiatric
      residents with the newly mandated Clinical Skills Verification (CSV) process. The
      goal was to identify and suggest remedies to any problems with the implementation
      of CSV in order to facilitate its success as an evaluation tool with all the
      three groups of residents. METHOD: The authors designed a 51-item survey
      questionnaire to gather demographic data and information about three principal
      content areas: 1) views on the effectiveness of the program; 2) the assessment
      experience; and 3) evaluation and feedback. A link to the survey was e-mailed to
      the directors of nine general-psychiatry residency programs in the United States
      with a request to forward it to the residents. The data were collected from
      February 2010 through March 2010. RESULTS: Sixty-three general-psychiatry
      residents (51.2% of 123 eligible residents) from nine selected programs completed
      the entire survey. Both IMG and USMG residents felt that the CSV was helpful in
      improving their clinical skills. Both groups of IMG residents, in contrast to
      their USMG counterparts, wanted more supervised interviews and were more likely
      to experience feedback as excessively negative and critical. In comparison to
      USMGs and US-IMGs, F-IMGs were less comfortable conducting an observed interview.
      They also had had less exposure to and experience with the CSV processes before
      their residency. CONCLUSIONS: Most residents reported positive experiences with
      the CSV. The survey also revealed notable commonalities and differences between
      IMG and USMG residents in their experiences and perceptions of the CSV process,
      mostly related to their cultural and medical school backgrounds. Authors
      recommend that residency programs take definitive steps toward addressing the
      unique needs of these groups of residents.

PMID- 22851031
TI  - Identifying and addressing stresses in international medical graduates.
AB  - OBJECTIVES: International medical graduates (IMGs), by definition, move from the
      country in which they received their training to another country in which to
      train and/or settle down. This process of migration and subsequent adjustment can
      lead to a number of issues that affect personal functioning and response to the
      new country. METHOD: The authors carried out a literature review to ascertain
      which factors may cause stress and which factors may contribute to successful
      adjustment by the IMGs. RESULTS: The reasons for migration by IMGs can be
      political, educational, or economic. Each reason brings with it a series of
      difficulties, both for the individual and the society to which they move, as well
      as the society they leave behind. It is inevitable that acculturation and
      settling down will raise specific issues in the functioning of the IMGs.
      CONCLUSIONS: In this article, the authors highlight some of the factors related
      to migration by IMGs and make suggestions on how to support them and help reduce
      their stress.

PMID- 22851032
TI  - Implementing a global child mental health observership program in a children's
      hospital: lessons learned.

PMID- 22851033
TI  - Problem-based learning in child and adolescent psychiatry at Trinity College,
      Dublin, Ireland.

PMID- 22851034
TI  - "The Wizard of Oz:" a depiction of TBI-related neurobehavioral syndromes.

PMID- 22851035
TI  - A changing DSM: the perspective of a trainee.

PMID- 22851036
TI  - Telepsychiatry.

PMID- 22851037
TI  - Robust co-regulation of tyrosine phosphorylation sites on proteins reveals novel
      protein interactions.
AB  - Cell signaling networks propagate information from extracellular cues via dynamic
      modulation of protein-protein interactions in a context-dependent manner.
      Networks based on receptor tyrosine kinases (RTKs), for example, phosphorylate
      intracellular proteins in response to extracellular ligands, resulting in dynamic
      protein-protein interactions that drive phenotypic changes. Most commonly used
      methods for discovering these protein-protein interactions, however, are
      optimized for detecting stable, longer-lived complexes, rather than the type of
      transient interactions that are essential components of dynamic signaling
      networks such as those mediated by RTKs. Substrate phosphorylation downstream of
      RTK activation modifies substrate activity and induces phospho-specific binding
      interactions, resulting in the formation of large transient macromolecular
      signaling complexes. Since protein complex formation should follow the trajectory
      of events that drive it, we reasoned that mining phosphoproteomic datasets for
      highly similar dynamic behavior of measured phosphorylation sites on different
      proteins could be used to predict novel, transient protein-protein interactions
      that had not been previously identified. We applied this method to explore
      signaling events downstream of EGFR stimulation. Our computational analysis of
      robustly co-regulated phosphorylation sites, based on multiple clustering
      analysis of quantitative time-resolved mass-spectrometry phosphoproteomic data,
      not only identified known sitewise-specific recruitment of proteins to EGFR, but
      also predicted novel, a priori interactions. A particularly intriguing prediction
      of EGFR interaction with the cytoskeleton-associated protein PDLIM1 was verified
      within cells using co-immunoprecipitation and in situ proximity ligation assays.
      Our approach thus offers a new way to discover protein-protein interactions in a
      dynamic context- and phosphorylation site-specific manner.

PMID- 22851038
TI  - Keratin expression in breast cancers.
AB  - Cytokeratin (CK) immunohistochemistry can play an important role in breast
      carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs
      in a large cohort of breast cancers and assessed its correlation with other
      biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was
      observed in more than 90 % of all breast carcinomas in this study, confirming
      their efficacy in immunohistochemical identification of breast cancer. A
      combination of CK8 and CK7 gave the highest sensitivity for detection of a minute
      number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and
      CK20, correlated positively with high tumour grade. The expression of CK5/6 and
      CK14 in a significant number of high-grade tumours raised concern regarding the
      use of absence of their expression to identify breast carcinoma. For
      identification of the basal subtype, CK5/6 gave a higher detection rate than
      CK14. CK20 expression was found more frequently than reported in previous
      studies, might constitute an indicator of poor prognosis and may be associated
      with the molecular apocrine subtype. This study highlights the diagnostic and
      prognostic relevance of the unique CK expression patterns in breast cancer.

PMID- 22851039
TI  - Intestinal spirochetosis: an enigmatic disease.
AB  - INTRODUCTION: Intestinal spirochetosis (IS) is a condition in which colonic and
      appendiceal epithelial cells are colonized by one of two anaerobic spirochetes,
      either the Brachyspira aalborgi or Brachyspira pilosicoli. There is much debate
      in the literature as to whether IS is a pathogen or a commensal inhabitant. A
      recent case of IS at our institution prompted a retrospective database search and
      review of the literature. METHODS: A pathology database search for IS was
      performed at Carolinas Medical Center from 2003 through 2007. After patient
      identification, a retrospective review of the endoscopic record and the pathology
      report was performed. Pathology slides were reviewed for accuracy and special
      silver stains and/or immunostains were performed if needed. The following data
      were collected for each patient when available: age, gender, nationality, HIV
      status, and other co-morbid conditions when noted. We attempted to determine
      whether patients were treated for spirochetosis and if so, the treatment regimen
      used as well as the results. RESULTS: The database search detected 29 patients
      with biopsies showing IS. Three patients were subsequently removed due to
      incorrect identification. A total of 26 patients with an average age of 45 years
      were reviewed. The most common symptoms were abdominal pain, diarrhea, and rectal
      bleeding. Most patients did not exhibit inflammatory changes despite the presence
      of spirochetosis. Pathologic examination revealed a relative increase in intra
      epithelial lymphocytes in a subset of cases, a non-specific finding. Acute
      colitis or architectural distortion was not seen in any of the study cases. We
      were only able to obtain follow-up of two patients after treatment with
      metronidazole and both responded to therapy. CONCLUSIONS: To date, our study is
      the largest case series that includes both endoscopic and pathologic descriptions
      and confirms the "bland" nature of the condition. In <20 % of our patients
      inflammation was present microscopically and it did not correlate well with
      endoscopic appearance. Symptoms reported by our patients were similar to those
      reported in previous studies, although our lack of endoscopic changes was
      different from one previous paper. There is no established standard of care for
      the treatment of IS and our study, reflects the enigmatic nature of IS as a
      disease process. In the absence of rigorous literature, physicians will need to
      use a logical and pragmatic approach to the evaluation and treatment of IS.

PMID- 22851040
TI  - Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with
      ulcerative colitis.
AB  - BACKGROUND: Immune balances are important for many diseases including ulcerative
      colitis (UC). This study aimed to explore the role of the balance between CD8+
      CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC.
      METHODS: Sixteen patients with UC, 16 patients with irritable bowel syndrome
      (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and
      CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using
      flow cytometry and immunofluorescent, respectively. The cytokines of the two
      lymphocytes were detected by protein chips and ELISA. The expression of the
      signal transducers, the JAK3 and STAT6, as well the transcription factors, the
      NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry.
      RESULTS: For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together
      with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon
      tissue, were significantly lower than those in both IBS patients and healthy
      volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon
      tissue of the UC patients were significantly higher than the other two groups.
      The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC
      patients, were significantly lower when compared with the other two groups.
      Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3
      and NFATc2 in UC patients, were significantly higher than both IBS and control
      group. CONCLUSIONS: The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a
      vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is
      beneficial for patients with UC.

PMID- 22851041
TI  - Classification of menstrual bleeding disorders.
AB  - There exists a spectrum of potential causes of abnormal uterine bleeding (AUB) in
      nonpregnant reproductive-aged women. In some instances the abnormal bleeding may
      emanate from definable pathologic entities in the endometrial cavity such as
      polyps or submucous leiomyomas (fibroids), while in others, it may occur
      secondary to coagulopathies or disorders of local or systemic hemostasis. If the
      patient is subjected to a rigorous evaluation more than one potential contributor
      may be identified, a circumstance that challenges the clinician since entities
      such as polyps, leiomyomas, and adenomyosis may frequently be asymptomatic, even
      in women with AUB. The bench or clinical investigator may also be influenced by
      the existence of the multiplicity of potential causes that could confound the
      results of research. This paper describes FIGO's (Federation Internationale de
      Gynecologie et d'Obstetrique) new PALM-COEIN classification of causes of AUB in
      the reproductive years (Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia
      Coagulopathy, Ovulatory disorder, Endometrial, Iatrogenic, Not yet classified).
      This system is designed to assist clinicians in the evaluation of patients,
      investigators in the design and interpretation of research and faculty in the
      education of medical students and residents/trainees. Additionally, given the
      longstanding existence of a confusing array of conflicting definitions, the
      manuscript describes the FIGO standardized terminology for both normal
      menstruation and AUB symptoms.

PMID- 22851042
TI  - Epithelial cells, the "switchboard" of respiratory immune defense responses:
      effects of air pollutants.
AB  - "Epimmunome", a term introduced recently by Swamy and colleagues, describes all
      molecules and pathways used by epithelial cells (ECs) to instruct immune cells.
      Today, we know that ECs are among the first sites within the human body to be
      exposed to pathogens (such as influenza viruses) and that the release of
      chemokine and cytokines by ECs is influenced by inhaled agents. The role of the
      ECs as a switchboard to initiate and regulate immune responses is altered through
      air pollutant exposure, such as ozone, tobacco smoke and diesel exhaust
      emissions. The details of the interplay between ECs and immune cells are not yet
      fully understood and need to be investigated further. Co-culture models, cell
      specific genetically-modified mice and the analysis of human biopsies provide
      great tools to gain knowledge about potential mechanisms. Increasing our
      understanding about the role of ECs in respiratory immunity may yield novel
      therapeutic targets to modulate downstream diseases.

PMID- 22851045
TI  - Multimedia support for improving preoperative patient education: a randomized
      controlled trial using the example of radical prostatectomy.
AB  - BACKGROUND: Growing evidence supports the use of multimedia presentations for
      informing patients. Therefore, we supported preoperative education by adding a
      multimedia tool and examined the effects in a randomized controlled trial.
      METHODS: We randomized German-speaking patients scheduled for radical
      prostatectomy at our center to receive either a multimedia-supported (MME) or a
      standard education (SE). Outcomes were measured in a structured interview.
      Primary outcome was patient satisfaction. In addition, we applied validated
      instruments to determine anxiety and measures of decision-making. Results were
      given by mean and standard deviation. For comparison of groups we used t test and
      chi-square test. For an explorative analysis we applied multivariate logistic
      regression. RESULTS: We randomized 203 patients to receive MME (n=102) or SE
      (n=101). Complete satisfaction with preoperative education was more frequent in
      the MME group (69 vs 52%, p=.016) and patients after MME reported more questions
      (5.7 vs 4.2, p=.018). There was no difference concerning the duration of talks
      and the number of recalled risks. However, perceived knowledge was higher after
      MME (1.3 vs 1.6, p=.037). Anxiety and measures of decision-making were
      comparable. Patients judged the multimedia tool very positive, and 74% of the MME
      group thought that their preoperative education had been superior to SE.
      CONCLUSIONS: Multimedia support should be considered worthwhile for improving the
      informed consent process before surgery (www.germanctr.de; DRKS00000096).

PMID- 22851046
TI  - Clinical cancer genome and precision medicine.
AB  - Revolutionary sequencing technologies have changed biomedical research and life
      science exponentially. Revealing the whole landscape of causal somatic and
      inherited mutations underlying individual patient's cancer sample by whole-genome
      sequencing (WGS) and whole-exome sequencing (WES) can lead to not only a new
      mutations-based taxonomy of solid tumors (Stratton, Science 331:1553-1558, 2011).
      But also shapes a roadmap for precision medicine (Roychowdhury et al., Sci Transl
      Med 3:111ra121, 2011; Roukos, Expert Rev Mol Diagn 12:215-218, 2012; Mirnezami et
      al., N Engl J Med 366:489-491, 2012). This inevitable approach for personalized
      diagnostics in concert with free-falling genome sequencing costs raises now the
      question of applying next-generation sequencing (NGS) technology in the clinic.
      In the pragmatic clinical world and in contrast to innovative research, is NGS
      based clinical evidence sufficient for decision-making on tailoring the best
      available treatment to the individual cancer patient?

PMID- 22851043
TI  - Social context induces two unique patterns of c-Fos expression in adolescent and
      adult rats.
AB  - The study assessed possible age differences in brain activation patterns to low
      dose ethanol (.5 g/kg intraperitoneally) and the influence of social context on
      this activation. Early adolescent or young adult male Sprague-Dawley rats were
      placed either alone or with an unfamiliar partner of the same age and sex
      following saline or ethanol administration. c-Fos protein immunoreactivity was
      used to index neuronal activation in 15 regions of interest. Ethanol had little
      effect on c-Fos activation. In adolescents, social context activated an
      "autonomic" network including the basolateral and central amygdala, bed nucleus
      of the stria terminalis, lateral hypothalamus, and lateral septum. In contrast,
      when adult rats were alone, activation was evident in a "reward" network that
      included the substantia nigra, nucleus accumbens, anterior cingulate and
      orbitofrontal cortices, lateral parabrachial nucleus, and locus coeruleus.

PMID- 22851044
TI  - Genetics and the individualized prediction of fracture.
AB  - Recent genome-wide association studies have identified many genetic variants
      associated with fracture risk. These genetic variants are common in the general
      population but have very modest effect sizes. A remaining challenge is to
      translate these genetic variant discoveries to better predict the risk of
      fracture based on an individual's genetic profile (ie, individualized risk
      assessment). Empirical and simulation studies have shown that 1) the utility of a
      single genetic variant for fracture risk assessment is very limited; but 2) a
      profile of 50 genetic variants, each with odds ratio ranging from 1.02 to 1.15,
      can improve the accuracy of fracture prediction and classification beyond that
      obtained by conventional clinical risk factors. These results are consistent with
      the view that genetic profiling, when integrated in existing risk assessment
      models, can inform a more accurate prediction of fracture risk in an individual.

PMID- 22851047
TI  - Guidelines for extended lymphadenectomy in gastric cancer: a prospective
      comparative study.
AB  - AIMS: To assess the efficacy of extended lymph node dissection in gastric cancer
      and to identify factors affecting lymph node detection. METHODS: A prospective
      study of 126 gastric cancer patients was conducted. Patients eligible for
      curative resection received total gastrectomy and extended lymphadenectomy (D2)
      and paraaortic lymph node sampling as the standard of care (study group).
      Supramesocolic total lymphadenectomy of the upper gastrointestinal tract was
      performed on 23 autopsy cases as a control group. RESULTS: Fifty-five gastric
      carcinoma patients were included in the study group. Median age was 58 years
      (range 31-80 years); 14 patients were female (25%), and 41 were male (75%). The
      median number of lymph nodes harvested from the specimen was 47 (24-95), and the
      median number of metastatic lymph nodes was 15 (1-71). In contrast, in the
      autopsy comparative group, the median number of harvested lymph nodes was 72 (50
      91). The median number of stational lymph nodes excised (lymph nodes excised from
      stations 4, 5, 10, 11, 12, and 16) was significantly higher in the control group
      than in the study group (P<0.05). Lymph node detection was adversely affected by
      body mass index (BMI) (P<0.03). In the study group, stations 5, 12, 11, and 10
      had the highest lymph node absence (LNA) (noncompliance) ratio with percentages
      of 53, 36, 33, and 22%, respectively. In the autopsy group, LNA (noncompliance)
      was not detected. CONCLUSIONS: Lymph nodes should be dissected by surgeons with
      sufficient technical and anatomical experience, and then examined and counted by
      experienced pathologists to reduce the occurrence of LNA. The results of this
      anatomical study can serve as a guideline to assess the success of lymph node
      dissection during gastric cancer surgery. Similar studies should be conducted in
      every country to establish national guidelines.

PMID- 22851048
TI  - Cost comparison of radiation treatment options after lumpectomy for breast
      cancer.
AB  - BACKGROUND: Radiation therapy (RT) after lumpectomy for breast cancer can be
      delivered with several different regimens. We evaluated a cost-minimization
      strategy to select among RT options. METHODS: An institutional review board (IRB)
      approved retrospective review identified a sample of 100 women who underwent
      lumpectomy for invasive or in situ breast cancer during 2009. Post lumpectomy RT
      options included: no radiation in women >=70 years [T1N0, estrogen receptor
      (ER)+] per Cancer and Leukemia Group B (CALGB) 9343 (no-RT), accelerated external
      beam partial-breast irradiation (APBI), and Canadian fractionation (C-RT), as
      alternatives to standard whole-breast radiation therapy (WBRT). Eligibility for
      RT regimens was based on published criteria. RT costs were estimated using the
      2011 US Medicare Physician Fee Schedule and average Current Procedural
      Terminology (CPT) codes billed per regimen at our institution. Costs were modeled
      in a 1,000-patient theoretical cohort. RESULTS: Median patient age was 56.5 years
      (range 32-93 years). Tumor histology included invasive ductal cancer (78 %),
      ductal carcinoma in situ (DCIS) (15 %), invasive lobular cancer (6 %), and mixed
      histology (1 %). Median tumor size was 1 cm (range 0.2-5 cm). Estimated per
      patient cost of radiation was US$5,341.81 for APBI, US$9,121.98 for C-RT, and
      US$13,358.37 for WBRT. When patients received the least expensive radiation
      regimen for which they were eligible, 14 % received no-RT, 44 % received APBI, 7
      % received C-RT, and 35 % defaulted to WBRT. Using a cost-minimization strategy,
      estimated RT costs were US$7.67 million, versus US$13.36 million had all patients
      received WBRT, representing cost savings of US$5.69 million per 1,000 patients
      treated. CONCLUSIONS: A cost-minimization strategy results in a 43 % reduction in
      estimated radiation costs among women undergoing breast conservation.

PMID- 22851049
TI  - Distress and coping strategies among patients with skin cancer.
AB  - Non-melanoma skin cancer (NMSC) is the most common cancer world-wide, yet few
      studies have investigated the psychosocial implications of this disease. The
      current study provides an account of the distress experienced by patients with
      NMSC and the coping strategies they use to deal with the NMSC diagnosis. The
      results demonstrate that 19 % of the patients experience significant levels of
      psychological distress. Furthermore, those who engaged in avoidant coping
      strategies (specifically behavioural avoidance) were more likely to experience
      distress. These findings highlight the importance of further investigating this
      patient population, since patients report difficulties adjusting to this disease
      and its treatment.

PMID- 22851050
TI  - New insights on the role of free D-aspartate in the mammalian brain.
AB  - Free D-aspartate (D-Asp) occurs in substantial amounts in the brain at the
      embryonic phase and in the first few postnatal days, and strongly decreases in
      adulthood. Temporal reduction of D-Asp levels depends on the postnatal onset of D
      aspartate oxidase (DDO) activity, the only enzyme able to selectively degrade
      this D-amino acid. Several results indicate that D-Asp binds and activates N
      methyl-D-aspartate receptors (NMDARs). Accordingly, recent studies have
      demonstrated that deregulated, higher levels of D-Asp, in knockout mice for Ddo
      gene and in D-Asp-treated mice, modulate hippocampal NMDAR-dependent long-term
      potentiation (LTP) and spatial memory. Moreover, similarly to D-serine,
      administration of D-Asp to old mice is able to rescue the physiological age
      related decay of hippocampal LTP. In agreement with a neuromodulatory action of D
      Asp on NMDARs, increased levels of this D-amino acid completely suppress long
      term depression at corticostriatal synapses and attenuate the prepulse inhibition
      deficits produced in mice by the psychotomimetic drugs, amphetamine and MK-801.
      Based on the evidence which points to the ability of D-Asp to act as an
      endogenous agonist on NMDARs and considering the abundance of D-Asp during
      prenatal and early life, future studies will be crucial to address the effect of
      this molecule in the developmental processes of the brain controlled by the
      activation of NMDARs.

PMID- 22851051
TI  - Synthesis of a conformationally constrained delta-amino acid building block.
AB  - Conformationally restricted amino acids are important components in
      peptidomimetics and drug design. Herein, we describe the synthesis of a novel,
      non-proteinogenic constrained delta amino acid containing a cyclobutane ring, cis
      3(aminomethyl)cyclobutane carboxylic acid (ACCA). The synthesis of the target
      amino acid was achieved in seven steps, with the key reaction being a base
      induced intramolecular nucleophilic substitution. A small library of dipeptides
      was prepared through the coupling of ACCA with proteinogenic amino acids.

PMID- 22851052
TI  - A similarity distance of diversity measure for discriminating mesophilic and
      thermophilic proteins.
AB  - The successful prediction of thermophilic proteins is useful for designing stable
      enzymes that are functional at high temperature. We have used the increment of
      diversity (ID), a novel amino acid composition-based similarity distance, in a 2
      class K-nearest neighbor classifier to classify thermophilic and mesophilic
      proteins. And the KNN-ID classifier was successfully developed to predict the
      thermophilic proteins. Instead of extracting features from protein sequences as
      done previously, our approach was based on a diversity measure of symbol
      sequences. The similarity distance between each pair of protein sequences was
      first calculated to quantitatively measure the similarity level of one given
      sequence and the other. The query protein is then determined using the K-nearest
      neighbor algorithm. Comparisons with multiple recently published methods showed
      that the KNN-ID proposed in this study outperforms the other methods. The
      improved predictive performance indicated it is a simple and effective classifier
      for discriminating thermophilic and mesophilic proteins. At last, the influence
      of protein length and protein identity on prediction accuracy was discussed
      further. The prediction model and dataset used in this article can be freely
      downloaded from http://wlxy.imu.edu.cn/college/biostation/fuwu/KNN-ID/index.htm .

PMID- 22851053
TI  - Multifunctional magnetic calcium phosphate nanoparticles for targeted platin
      delivery.
AB  - Magnetic mesoporous amorphous calcium phosphate nanoparticles with a size of 62
      nm and abundant -COOH groups on the surface have been prepared by a simple
      method. The particles show excellent aqueous dispersion stability in
      physiological pH without any deterioration in hydrodynamic size and
      zetapotential. By virtue of the carboxylate groups on the surface, the platinum
      pharmacophore cis-diaquadiamine platinum(II), folic acid and rhodamine
      isothiocyanate were conjugated on these magnetic calcium phosphate nanoparticles.
      The cytotoxicity and internalization efficiency of these nanocarriers have been
      evaluated on folate receptor overexpressed HeLa cells. These drug loaded
      nanoagents exhibit elevated cytotoxicity and induce apoptosis in HeLa cells.

PMID- 22851054
TI  - Kinetics and stereochemistry of hydrolysis of an N-(phenylacetyl)-alpha
      hydroxyglycine ester catalyzed by serine beta-lactamases and DD-peptidases.
AB  - The alpha-hydroxydepsipeptide 3-carboxyphenyl N-(phenylacetyl)-alpha
      hydroxyglycinate (5) is a quite effective substrate of serine beta-lactamases and
      low molecular mass DD-peptidases. The class C P99 and ampC beta-lactamases
      catalyze the hydrolysis of both enantiomers of 5, although they show a strong
      preference for one of them. The class A TEM-2 and class D OXA-1 beta-lactamases
      and the Streptomyces R61 and Actinomadura R39 DD-peptidases catalyze hydrolysis
      of only one enantiomer of at any significant rate. Experiments show that all of
      the above enzymes strongly prefer the same enantiomer, a surprising result since
      beta-lactamases usually prefer L(S) enantiomers and DD-peptidases D(R). Product
      analysis, employing peptidylglycine alpha-amidating lyase, showed that the
      preferred enantiomer is D(R). Thus, it is the beta-lactamases that have switched
      preference rather than the DD-peptidases. Molecular modeling of the P99 beta
      lactamase active site suggests that the alpha-hydroxyl 5 of may interact with
      conserved Asn and Lys residues. Both alpha-hydroxy and alpha-amido substituents
      on a glycine ester substrate can therefore enhance its productive interaction
      with the beta-lactamase active site, although their effects are not additive;
      this may also be true for inhibitors.

PMID- 22851055
TI  - Clinical studies of acute myeloid leukemia in the Japan Adult Leukemia Study
      Group.
AB  - Acute myeloid leukemia (AML) is the most common adult leukemia in Japan. The
      treatment for AML consists of induction, consolidation, and maintenance
      therapies. To improve outcomes in the treatment of AML, the Japan Adult Leukemia
      Study Group has conducted six studies in AML patients aged 15-64 years since
      1987. In AML201 study, IDR (12 mg/m(2)/day for 3 days) or DNR (50 mg/m(2)/day for
      5 days) in combination with Ara-C (100 mg/m(2)/day continuous infusion for 7
      days) was established as the standard induction therapy, and four courses of
      combination chemotherapy using non-cross-resistant agents for non-core binding
      factor (CBF) AML or three courses of high-dose Ara-C for CBF AML was established
      as the standard consolidation therapy. The AML97 study showed that allo-HSCT from
      an HLA-identical sibling donor reduced relapse incidence and improved disease
      free survival (DFS), but did not significantly impact overall survival (OS) in
      poor or intermediate risk patients. Despite these studies by JALSG, only about
      one-third of AML patients remain free of disease for more than 7 years. The JALSG
      is now conducting the AML209 study to adapt individual therapies according to
      genetic alterations.

PMID- 22851056
TI  - Prolonged remission from eltrombopag in chronic refractory idiopathic
      thrombocytopenic purpura.
AB  - The therapy of ITP has recently been revolutionized with the introduction of
      thrombopoeitin stimulating agents. However, these medications are known to
      increase the platelet count only while the medication is being administered, with
      a rapid fall of the platelet count to baseline pre-therapy levels on
      discontinuation. We report the case of a patient with chronic refractory ITP who
      has attained a prolonged remission after a short course of eltrombopag, with
      normalization of the platelet count, which is sustained 8 months after
      discontinuation of the medication.

PMID- 22851057
TI  - Interaction of water with the G-quadruplex loop contributes to the binding energy
      of G-quadruplex to protein.
AB  - Unlike DNA duplexes that release water upon interaction with protein, the binding
      of DNA G-quadruplex of the thrombin-binding aptamer (TBA) to thrombin takes up
      water. Here, to reveal the mechanism of water uptake, we designed four mutants of
      TBA (DeltaT3, DeltaT7, DeltaT9, DeltaT12), in which thymine residues (T3, T7, T9
      and T12) were deleted from the loop regions of TBA G-quadruplex. For the mutants
      the thermodynamics and the osmolyte effects on the interactions with thrombin
      were investigated. The mutants DeltaT3, DeltaT9 and DeltaT12 decreased the
      binding constants of the G-quadruplex to thrombin. Furthermore, an osmotic stress
      analysis indicated that the number of water molecules binding to the complex
      decreased in the mutants DeltaT3 and DeltaT9. The decrease in the binding
      affinity was related to loss of binding of the loop nucleotides to water
      molecules. Therefore, the interaction between loops of the G-quadruplex and water
      molecules contributed to the binding energy of G-quadruplex to protein. Our study
      suggests that water binding is essential for the binding of G-quadruplex to
      protein.

PMID- 22851060
TI  - [How to improve the level of endoscopic diagnosis and treatment of early
      gastrointestinal cancer: private opinions].
AB  - At present, the level of diagnosis and treatment of early gastrointestinal cancer
      has a larger gap between China and developed countries. In recent years, the
      advent of new endoscopic imaging techniques has improved the detection rate of
      early gastrointestinal cancer. Along with this, endoscopic submucosal
      dissection(ESD) enables radical resection for early cancer. In this article, we
      discuss how to improve the level of endoscopic diagnosis and treatment of early
      gastrointestinal cancer.

PMID- 22851059
TI  - Perioperative assessment of platelet function by Thromboelastograph Platelet
      Mapping in cardiovascular patients undergoing non-cardiac surgery.
AB  - Five percent of patients on dual antiplatelet therapy after coronary artery stent
      implantation will need non-cardiac surgery within the first year of therapy, and
      many more will need surgery later on. A function assay that evaluates platelet
      reactivity and inhibition by drug therapy is beneficial for such patients.
      Platelet Mapping assay (PM) using the TEG analyzer was tested in surgical
      patients. After IRB approval, 60 patients on combined aspirin and clopidogrel
      therapy were consented and enrolled. The TEG maximal amplitude (MA) and the
      percentage (%) platelet inhibition were recorded and analyzed. Fifty-seven
      patients (mean age 65.7 +/- 10.9 years) had preoperative data only. Distribution
      of preoperative ADP (43.6 +/- 24.4%) and AA inhibition (52.8 +/- 30.2%) was
      determined, as well as for the preoperative MA ADP (43.1 +/- 15.9 mm) and MA AA
      (37.2 +/- 19.6 mm), showing an offset of the effect of both medications starting
      from day 3. Patients with complete pre- and postoperative data were stratified
      depending on duration off antiplatelet therapy (<=3 days, 3-7 days and >7 days):
      n = 27, ADP % preop inhibition (43.2 +/- 21.6%), ADP % postop inhibition (32.3 +/
      18.3%), p = 0.048. Distribution of immediate pre- and post- ADP and AA %
      inhibitions, showing a possible reduction in Delta of inhibition for clopidogrel
      at 3 days, were also assessed. CONCLUSION: According to the findings, the TEG PM
      assay might be a feasible approach to objectively evaluate the effects of aspirin
      and clopidogrel during the perioperative period and potentially guide drug
      management.

PMID- 22851058
TI  - Brain structures associated with executive functions during everyday events in a
      non-clinical sample.
AB  - Executive functions involve control processes such as goal-oriented planning,
      flexible strategy generation, sustaining set maintenance, self-monitoring, and
      inhibition. Executive functions during everyday events (EFEEs) are distinct from
      those measured under laboratory settings; the former can be severely impaired
      while the latter remain intact. Non-routine everyday problems due to executive
      dysfunctions affect individual functioning in everyday life and are of great
      clinical interest. Despite the importance of anatomical bases underlying better
      EFEEs, such bases have never been investigated among non-clinical samples. Using
      voxel-based morphometry to measure regional gray matter volume (rGMV) and
      regional white matter volume (rWMV) and diffusion tensor imaging to determine
      fractional anisotropy values, we identified the anatomical correlates of better
      EFEEs using the Dysexecutive Questionnaire in 303 normal young subjects (168 men
      and 135 women). Better EFEEs were associated with a smaller rGMV in the
      orbitofrontal cortex (OFC) spread across Brodmann areas (BA) 25, 11, and 12 and
      larger rWMV in the WM area of OFC adjacent to BA 11. Furthermore, individual
      EFEEs were positively associated with rWMV in the temporal areas, primarily the
      inferior longitudinal fasciculus and inferior fronto-occipital fasciculus, the
      latter of which connects OFC and posterior regions. Thus, our findings suggest
      that brain structures involving OFC, together with other regions, contribute to
      the maintenance of effective EFEEs among non-clinical subjects. 

PMID- 22851061
TI  - [Endoscopic sclerotherapy of gastric varices by tissue adhesives].
AB  - The diagnosis and treatment of gastric varices is a clinically concerned issue.
      With the development of endoscopic technology. The success rate of controlling
      bleeding from gastric and esophageal varices has been improved a lot. It is
      efficacious and safe to treat gastric and esophageal varices by endoscopic
      injection of tissue adhesives and to prevent re-bleeding. There is few acute and
      long-term complications of this modality. It has been the first line treatment
      for gastric varices.

PMID- 22851062
TI  - [Endoscopy in the diagnosis and management of esophageal motility disorders].
AB  - With the development of optics and mechanics, endoscopic technologies are not
      only used as a simple diagnostic method, but also applied in therapy. Since the
      beginning of the 21st century, minimally invasive medicine has become the
      development trend. Many novel technologies have appeared, such as endoscopic
      mucosal resection, endoscopic submucosal dissection, and peroral endoscopic
      myotomy. Esophageal motility disorders are common diseases in clinic, which
      seriously affect the quality of life. Although esophageal manometry is the golden
      diagnostic standard, endoscopy also plays an important role in diagnosis. There
      are many therapeutic methods in achalasia and gastroesophageal reflux diseases
      with good efficacy, while the therapy in other esophageal motility disorders
      remains in dispute. According to the domestic and foreign research progressions,
      we introduce the role of endoscopy in the diagnosis and management of esophageal
      motility disorders.

PMID- 22851063
TI  - [Clinical value of tunnel endoscopy for the treatment of esophagogastric
      diseases].
AB  - Tunnel endoscopy is a new therapeutic technique developed from natural orifice
      endoscopic transluminal surgery and endoscopic submucosal dissection. With the
      quick development in the passing 5 years, tunnel endoscopy has been applied in
      the treatment of clinical diseases. In this article, our aim was to clarify the
      indication and method, evaluate the efficacy and safety of tunnel endoscopy for
      the treatment of esophagogastric diseases, including esophageal achalasia and
      submucosal tumors originating from the muscularis propria layer.

PMID- 22851064
TI  - [Clinical value of different magnifying chromoendoscopy methods in screening
      gastric precancerous lesions and early cancers].
AB  - OBJECTIVE: To prospectively evaluate the clinical value of different magnifying
      chromoendoscopy(MCE) methods in screening gastric precancerous lesions and early
      cancers. METHODS: Between March 2010 and October 2011, among all the patients
      aged over 40 who received esophagogastroduodenoscopy at Zhongshan hospital, Fudan
      University, suspicious lesion was detected in 699 patients, who were randomly
      assigned to three groups: epinephrine dye(n=240), indigo carmine dye(n=246), and
      acetic acid-indigo carmine mixture dye(n=213). Diagnosis was made according to
      surface patterns and microvessels of the lesion. Pathological diagnosis was used
      as the gold standard. The concordance between endoscopic diagnosis and
      pathological diagnosis was evaluated through the agreement(Kappa) test. McNemar
      Paired chi-square test was used to compare the concordance of three MCE methods,
      regular white light, magnification alone, and NBI magnifier before and after MCE.
      RESULTS: Pathological examination showed inflammatory lesions in 415 patients,
      intestinal metaplasia in 190, low grade intra-epithelial neoplasia in 17, and
      high grade intra-epithelial neoplasia or early cancer in 77. The percentage of
      patients with consistent endoscopic and pathological diagnosis was 77.1%(185/240)
      for epinephrine dye, 80.5%(198/246) for indigo carmine dye, and 81.2%(173/213)
      for acetic acid-indigo carmine mixture dye. Kappa values were 0.579, 0.502, and
      0.667 respectively(all P<0.01). For the screening of high grade intra-epithelial
      neoplasia or early cancer, the diagnostic sensitivities were 84.0%, 83.3%, and
      92.9%, respectively, and the specificities were 98.6%, 97.3%, and 98.4%. All the
      three chromoendoscopy methods improved the diagnostic accuracy for precancerous
      lesions compared with conventional gastroscopic observation with white light(all
      P<0.01). Indigo carmine and acid-indigo carmine mixture dye improved the
      diagnostic accuracy of magnification alone(both P<0.05). There was no significant
      difference in diagnostic accuracy between each MCE method and magnifying NBI
      observation(all P>0.05). CONCLUSION: NBI magnification and all the three MCE
      methods may improve the diagnostic accuracy of early gastric cancer and
      precancerous lesions.

PMID- 22851065
TI  - [Effects of peroral endoscopic myotomy on esophageal dynamics in patients with
      esophageal achalasia].
AB  - OBJECTIVE: To investigate the effects of peroral endoscopic myotomy(POEM) on
      esophageal dynamics in patients with esophageal achalasia. METHODS: From
      September 2011 to November 2011, 20 cases with esophageal achalasia received POEM
      at the Endoscopic Center in the Zhongshan Hospital of Fudan University. Pre
      operation esophageal dynamics of all the patients were evaluated by high
      resolution manometry(HRM) system and 3 days after operation the test was
      repeated. Lower esophagus sphincter resting pressure(LESP), 4-second integrated
      relaxation pressure(4sIRP), lower esophagus sphincter relax rate(LESRR), lower
      esophagus sphincter length(LESL), and esophageal manometry were analyzed.
      RESULTS: After POEM, LESP decreased from(29.1+/-17.0) mm Hg to(14.6+/-4.9) mm Hg,
      and decrease rate was 49.8%(P<0.01). However, the decreases in LESRR and LESL
      were not statistically significant(P>0.05). Esophageal peristaltic contraction
      was absent in all the 20 patients preoperatively. After POEM, changes in the
      esophageal contraction were seen in 7 patients, and peristalsis was noticed but
      was below normal level. There were no significant changes in peristalsis in the
      remaining 13 patients. CONCLUSION: POEM can significantly reduce LESP and 4sIRP
      in patients with achalasia, but can not affect the contraction of the esophagus.

PMID- 22851066
TI  - [Application and evaluation of submucosal tunneling endoscopic resection of
      gastric submucosal tumors originating from the muscularis propria layer].
AB  - OBJECTIVE: To evaluate the clinical value of submucosal tunneling endoscopic
      resection(STER) for gastric submucosal tumor(SMT) originating from the muscularis
      propria (MP) layer. METHODS: Clinicopathological data of 23 cases with gastric
      SMT originating from the MP layer treated with STER from September 2010 to
      December 2011 were analyzed retrospectively. RESULTS: There were 13 males and 10
      females. The age ranged from 28 to 73(mean, 52.4) years old. Of the 23 SMTs, 11
      were located in the cardia adjacent to the gastric body, 4 in the cardia adjacent
      to the fundus, 5 in the lesser curvature of gastric body and 3 in the gastric
      antrum of greater curvature. All the SMTs originating from the MP layer, 14 were
      located in the superficial MP layer and 9 in the deep MP layer(including 5
      gastric SMTs close to serosa). En bloc STER was performed successfully in all the
      patients. The mean lesion size was 2.1 cm(range 1.5-3.2 cm). The mean procedure
      time was 54.8 min(range 30-125 min). Pathological examination showed that the
      lesions were leiomyomas(n=10), stromal tumors(n=8), glomus tumor(n=2),
      Schwannoma(n=2), and calcifying fibrous tumor(n=1). Both lateral and vertical
      margins were negative in all the cases. Three patients developed pneumothorax and
      subcutaneous emphysema and 5 pneumoperitoneum. One patient developed effusion
      under the left half of the diaphragm and secondary infection. All of them
      recovered uneventfully after conservative treatments. No delayed bleeding or GI
      tract leakage was noticed. None of the 23 cases encountered submucosal hematoma
      or infection. No tumor residual or recurrence was found during the follow
      up(range, 3-18 months). CONCLUSIONS: STER is a safe, effective for appropriate
      lesions in the MP layer of the stomach. En bloc resection and accurate
      histopathological evaluations can be achieved.

PMID- 22851067
TI  - [Value of endoscopic submucosal dissection for duodenal lesions in 78 patients].
AB  - OBJECTIVE: To assess the clinical value of endoscopic submucosal dissection(ESD)
      for duodenal lesion. METHODS: A total of 78 patients with duodenal lesion were
      treated with ESD from November 2006 to August 2010. The clinical data were
      retrospectively analyzed. RESULTS: There were 46 male and 14 female patients. The
      mean age was(54+/-9) years. The lesion location included the duodenal bulb(n=39,
      50%), the junction of bulb and descending part(n=19, 24.4%), and the descending
      part(n=20, 25.8%). The mean diameter of the lesions was(2.1+/-1.7) cm. Fifty
      one(65.4%) lesions originated from the mucosa, including inflammatory/
      hyperplastic polyps(n=22, 28.2%), villous/tubular adenoma(n=26, 33.3%), and
      hamartomas polyps(n=3, 3.8%). Twenty-five(32.1%) lesions originated from the
      submucosa, including Brunner's glands adenoma(n=15, 19.2%), ectopic pancreas(n=3,
      3.8%), carcinoid tumor(n=3, 3.8%), lipoma(n=2, 2.6%), myxoinoma(n=1, 1.3%), and
      angio-lymphangioma(n=1, 1.3%). There were two lesions originated from the
      muscularis propria(n=2, 2.5%), and both were ectopic pancreas. All cases received
      ESD successfully. The mean operative time was(37+/-41) min and the mean blood
      loss was(23+/-15) ml. The perioperative complication rate was 35.9%(28/78),
      including intraoperative perforation(n=6), delayed perforation(n=3),
      intraoperative hemorrhage(n=10), delayed bleeding(n=7), and transient elevation
      of serum amylase(n=2). Postoperative pathological examination showed vascular
      invasion with tumor cells in one patient, who received extended resection later.
      The remaining 77 patients showed no recurrence during the followed up(rang, 3-23
      months) using endoscopy. CONCLUSION: ESD is an effective, safe, minimally
      invasive method for the management of duodenal lesions.

PMID- 22851068
TI  - [Feasibility of endoscopic full-thickness resection in the treatment of
      colorectal submucosal tumors].
AB  - OBJECTIVE: To investigate the feasibility and safety of endoscopic full-thickness
      resection(EFTR) in the treatment of colorectal submucosal tumor(SMT). METHODS:
      From September 2009 to March 2012, 4 cases with colorectal SMT received EFTR at
      the Endoscopic Center in the Zhongshan Hospital of Fudan University. The
      operative time, complications, and follow-up data were analyzed. RESULTS: There
      were 3 females and 1 male. The age ranged from 33 to 78 years. The tumor location
      included the upper rectum(n=2), the ascending colon(n=1), and the descending
      colon(n=1). The mean operative time was 48.0(24-80) min. The mean diameter was
      1.45(0.8-2.0) cm. Postoperative pathological examination revealed schwannoma,
      pneumatosis cystoides intestinalis, endometriosis, and mild hyperplasia of smooth
      muscle in the muscularis mucosa. There was no bleeding or perforation
      intraoperatively and postoperatively. Two patients developed abdominal pain and
      fever, one of whom had regional peritonitis and was managed by fasting and
      intravenous antibiotics. No surgical intervention was required. Postoperative
      follow up ranged from 1 to 30 months and no residual cancer or recurrence was
      found. CONCLUSION: EFTR is a safe and effective method for colorectal SMT.

PMID- 22851069
TI  - [Diagnosis and management of duodenal perforation after endoscopic retrograde
      cholangio-pancreatography: clinical analysis of 15 cases].
AB  - OBJECTIVE: To summarize the experience with duodenal perforations to determine a
      systematic management approach. METHODS: A total of 11 250 patients who received
      endoscopic retrograde cholangiopancreatography(ERCP) in The First People's
      Hospital of Hangzhou from January 2005 to December 2011 and 15(0.13%) patients
      developed duodenal perforation. The clinical data of these 15 cases were
      analyzed. RESULTS: There were 6 males and 9 females. The age ranged from 45 to 87
      years. Seven patients developed perforation after sphincterotomy of the duodenal
      papilla. Five patients perforated due to the endoscope, and 3 due to guide wire
      and net basket. All the patients presented  varying degree of abdominal pain and
      distention. CT scan of the upper abdomen showed peripancreatic and
      retroperitoneal air or fluid. Diagnosis was confirmed in 7 patients using
      abdominal X-ray. Eight patients developed postoperative abdominal pain and
      distention, subcutaneous emphysema, and fever 3 hours to 5 days after surgery,
      and diagnosis was confirmed using plain abdominal X-ray or upper abdominal CT
      scan. Nine patients were managed conservatively, 4 of whom were diagnosed within
      3 hours after perforation and were managed by endoscopic metal clip and
      nasobiliary drainage and no abdominal abscesses developed. The length of hospital
      stay ranged from 10 to 15 days. Five patients were diagnosed 10 hour to 5 days
      after perforation, of whom 2 had intestinal fistula, 4 had abscess, and one died,
      the length of hospital stay ranged from 15 to 105 days. Six patients were managed
      surgically, 4 received surgery within 4 to 8 hours after perforation and no
      abscess developed, and the length of hospital stay ranged from 18 to 21 days. The
      other 2 patients were operated at 24 hours and 30 hours after perforation
      respectively, one of whom had recurrent intra-abdominal bleeding after surgery
      and one died from intra-abdominal abscess and multiple organ failure.
      CONCLUSIONS: For duodenal perforations related to ERCP, early diagnosis can be
      made by prompt intraoperative identification and postoperative CT scan.
      Endoscopic metal clip and nasobiliary drainage should be considered aside from
      surgical intervention.

PMID- 22851070
TI  - [Clinical application of self-made drainage tube with balloon for iatrogenic
      colonic perforation].
AB  - OBJECTIVE: To investigate the clinical efficacy of colonic bypass drainage by
      self-made drainage tube with balloon for iatrogenic colonic perforation. METHODS:
      A retrospective analysis of 8 patients with iatrogenic colonic perforations from
      January 2009 to March 2011 was performed. Self-made drainage tubes with balloon
      were placed in the bowel lumen endoscopically after perforations were closed with
      endoclips or endoloops under endoscope. The inflatable balloon at the front-end
      of the tube was fixed at the mouth side of colonic perforation to achieve
      continuous drainage of stool and intestinal juice. RESULTS: Endoscopic bypass
      continuous drainage by using self-made drainage tube with balloon was
      successfully carried out in all the 8 patients. All the perforations healed and
      no surgical intervention required. Bypass drainage continued for 3-10 days(mean
      7.6 days). One patient received colonoscopy 3 days after the procedure, and
      displacement of the drainage tube was noticed requiring endoscopic adjustment.
      All the drainage tubes were removed uneventfully, and no ulceration or
      perforation occurred at balloon fixed site after removal. After follow up ranging
      from 12 to 36 months, no chronic fistula, adhesive obstruction, or abdominal
      infection occurred. CONCLUSION: Colonic bypass drainage by self-made drainage
      tube with balloon for iatrogenic colonic perforation is simple, feasible, safe
      and reliable.

PMID- 22851071
TI  - [Use of endoscopic tissue adhesive injection for gastric varices].
AB  - OBJECTIVE: To evaluate the long-term efficacy and safety of endoscopic tissue
      adhesive(N-octyl-alpha-cyanoacrylate) injection for the treatment of gastric
      varices. METHODS: A retrospective study was performed to review the clinical and
      follow up data of 169 patients with gastric variceal who received tissue adhesive
      injection at the Fudan University Affiliated Zhongshan Hospital between April
      2004 and December 2011. RESULTS: There were 128 males and 41 females with a mean
      age of 56.8(37-85) years old. One hundred and thirty-one patients received one
      injection, 38 received two injections or more with a mean of 1.12 per patient.
      Volume of injection ranged from 1 to 3 ml(mean, 1.7 ml). Eighty-three patients
      received adhesive injection alone, 231 received injection combined with ligation,
      50 received combined sclerotic agent injection. All the patients had follow up
      ranging from 1 to 78 months(mean, 3.4 months). The treatment outcome was
      satisfactory in 130 patients(76.9%), good in 36(21.3%), and ineffective in
      3(1.8%). The rate of ectopic embolization was 3.0%, and the rate of early re
      bleeding was 1.2%. Postoperatively there were no septic complications or
      esophageal stricture. There were no deaths within 2 weeks. CONCLUSION: Injection
      of tissue adhesive under endoscopic guidance for treatment of gastric varices is
      convenient, safe and effective.

PMID- 22851072
TI  - [Feasibility and safety of patient controlled analgesia technology in double
      balloon endoscopy].
AB  - OBJECTIVE: To evaluate the feasibility and safety of patient controlled analgesia
      (PCA) technology during double balloon endoscopy(DBE) inspection. METHODS:
      According to the anesthesia, 120 patients with suspected intestinal disease were
      randomized into non-anaesthesia(Group A), propofol infusion with TCI vein
      pump(Group B), and remifentanil vein infusion with PCA pump(Group C), with 40
      patients in each group. The feasibility and safety of the three methods in double
      balloon endoscopy(DBE) inspection were evaluated. RESULTS: The tolerance in
      groups B and C was good and the procedure success rate was 100%, significantly
      higher than Group A(80%, 12/40, P<0.01). The fluctuation of blood pressure, heart
      rate, and oxygen saturation was significantly greater in groups A and B, while
      patients in Group C remained stable. The detection rate was 67.5%(27/40) in Group
      B and 72.5%(29/40) in Group C, significantly higher than that in Group A(37.5%,
      15/40, all P<0.01). The depth of endoscope was longer and the length of hospital
      stay shorter in Group C as compared to Group B(both P<0.05). CONCLUSION: The
      application of PCA technology in the double-balloon endoscopy inspection can meet
      the individualized analgesic needs of patients in different period, increase the
      tolerance and compliance of patients to the inspection, facilitate patient
      operator communication and positions change, reduce the operation risk, and
      increase the success rate of double balloon endoscopy.

PMID- 22851073
TI  - [Meta-analysis of safety and efficacy of self-expending metallic stents as bridge
      to surgery versus emergency surgery for left-sided malignant colorectal
      obstruction].
AB  - OBJECTIVE: To evaluate the safety and efficacy of self-expending metallic stents
      (SEMS) as bridge to surgery versus emergency surgery for left-sided malignant
      colorectal obstruction. METHODS: A comprehensive literature search of CENTRAL,
      PubMed, EMBASE, Medline, Ovid LWW, CMB, CNKI and Wanfang Databases were performed
      for all randomized controlled trials or retrospective studies comparing self
      expending metallic stents as bridge to surgery(SABS group) with emergency surgery
      (ES group). A meta-analysis was carried out by RevMan5.1 software on the outcomes
      concerning safety and efficacy of the two groups. RESULTS: Fourteen studies
      matched the criteria including 1083 patients. Five were randomized controlled
      trials and nine were retrospective analysis. Compared with the ES group, the SABS
      group had a lower short-term mortality(RR=0.52, 95% CI:0.30-0.93, P<0.05), lower
      overall complications(RR=0.46, 95% CI:0.31-0.70, P<0.05), higher resection
      rate(RR=1.90, 95%CI:1.33-2.70, P<0.01), shorter operative time(MD=-59.77, 95%CI:
      87.51--32.04, P<0.01), and shorter interval to first flatus(MD=-10.78, 95%CI:
      16.67--4.90, P<0.01). There were no statistically significant differences between
      the two groups in permanent stomy and hospital stay. CONCLUSION: The safety and
      efficacy of self-expending metallic stents as bridge to surgery for left-sided
      malignant colorectal obstruction is superior to emergency surgery.

PMID- 22851074
TI  - [Comparison of (18)F-FDG PET-CT and abdomen enhancement CT in diagnosing
      peritoneal metastases].
AB  - OBJECTIVE: To compare the diagnostic value of (18)F-FDG PET-CT with abdomen
      contrast CT in the diagnosis of peritoneal metastases. METHODS: Between January
      2008 and May 2011, imaging results of 97 patients with suspicious peritoneal
      metastases were retrospectively reviewed, and all the patients underwent both
      abdomen contrast CT and (18)F-FDG PET-CT imaging. Final diagnosis was made by
      histopathology or follow up. RESULTS: Seventy-seven patients were verified as
      peritoneal metastases after pathological examination(n=88) or follow up(n=9),
      while the other 20 patients were absent. The sensitivity of (18)F-FDG PET-CT was
      90.9%(70/77), the specificity 85.0%(17/20), and the accuracy 89.7%(87/97). There
      were 3 false positive and 7 false negative. The sensitivity of contrast CT was
      66.2%(51/77), the specificity 80.0%(16/20), and the accuracy 69.1%(67/97). There
      were 4 false positive and 26 false negative. The difference in diagnostic
      accuracy was statistically significantly between these two methods(P<0.05).
      CONCLUSION: The diagnostic value of (18)F-FDG PET-CT is significantly higher than
      that of abdominal enhanced CT for peritoneal metastases.

PMID- 22851075
TI  - [Clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative
      TNM staging assessment of gastric carcinoma].
AB  - OBJECTIVE: To explore the clinical value of 64-slice spiral 3-phase CT enhanced
      scanning for preoperative TNM staging assessment of gastric carcinoma. METHODS: A
      retrospective study was performed to review the 64-slice spiral 3-phase CT
      enhanced scanning of 120 patients with gastric cancer diagnosed by biopsy prior
      to operation and postoperative pathological reports. All the findings were
      reviewed by two senior radiologic diagnosticians separately and compared with
      pathological findings. RESULTS: The accuracy of 64-slice spiral CT enhanced scan
      was 79.2%(95/120) for T staging, 66.7%(10/15) for T1, 66.7%(14/21) for T2,
      84.0%(42/50) for T3, and 85.3%(29/34) for T4. For gastric wall with single layer
      and multiple layers, the accuracy of CT enhanced scanning was 59.4%(19/32) and
      81.8%(72/88) for T staging, and the difference was statistically
      significant(P<0.05). The accuracy of 64-slice spiral CT enhanced scan was
      73.9%(85/115) for N staging, 75.5%(37/49) for N0, 70.3%(26/37) for N1,
      75.9%(22/29) for N2. The accuracy of 64-slice spiral CT enhanced scanning was
      89.2% for M staging. CONCLUSION: 64-slice spiral CT 3-phase enhanced scanning can
      monitor the invasion, lymphatic metastasis, and distant metastasis of gastric
      cancer dynamically, which may become an important examination item for the
      preoperative evaluation of gastric cancer.

PMID- 22851076
TI  - [Methylation status of CDH1 gene in preoperative abdominal lavage of patients
      with gastric cancer and its clinical significance].
AB  - OBJECTIVE: To explore the association between the progression of gastric cancer
      and the aberrant methylation of CDH1 gene in preoperative abdominal lavage fluid.
      METHODS: Real-time methylation-specific polymerase chain reaction(qMSP) was used
      to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands
      from preoperative abdominal lavage fluid in 92 patients with gastric cancer. The
      associations between methylation of CDH1 genes and clinicopathologic features and
      prognosis were investigated. RESULTS: Among the 92 patients with gastric cancer,
      aberrant methylation of CDH1 gene was detected in 45(48.9%) patients, including
      total aberrant methylation in 12(13.0%) cases and partly aberrant methylation in
      33(35.9%) cases. Significant associations were found between CDH1 methylation
      status and tumor size, growth pattern, differentiation, lymphovascular invasion,
      infiltration depth, lymph node metastasis, distant metastasis, and clinical
      staging(all P<0.05). However, there were no significant associations between CDH1
      methylation status with gender, age, tumor location, or Helicobacter pylori
      infection(all P>0.05). The median progression-free survival was 20 months for
      CDH1 methylation group and 38 months for non-methylated group, and the difference
      was statistically significant(P<0.01). Cox model analysis revealed that CDH1
      methylation status in preoperative peritoneal lavage fluid was an independent
      factor associated with postoperative survival in patients with gastric
      cancer(P=0.000, RR=332.88, 95%CI:21.71-5105.07). CONCLUSIONS: The aberrant
      methylation of 5'-CpG of CDH1 gene promoter is common in gastric cancer. The
      examination of CDH1 methylation status of abdominal lavage should be considered
      in the progression of gastric cancer.

PMID- 22851077
TI  - [Outcomes and defecation after one-stage transanal endorectal pull-through
      procedure for Hirschsprung disease].
AB  - OBJECTIVE: To evaluate the efficacy, safety, and defecation after one-stage
      transanal endorectal pull-through(TOSEPT) for Hirschsprung disease. METHODS:
      Clinical data of 56 patients with Hirschsprung disease undergoing TOSEPT in the
      Third Hospital of Guangzhou Medical College between 2005 and 2011 were
      retrospectively analyzed. According to age at operation, the patients were
      divided into newborn group(n=21, surgery performed within 1 month after birth)
      and non-newborn group(n=35). Recovery period was defined as the period required
      for normal defecation pattern after operation. Intraoperative and postoperative
      parameters were compared. RESULTS: The mean operative time was(121.5+/-39.2)
      minutes. The mean length of bowel resection was(17.6+/-4.2) cm. The mean
      intraoperative blood loss was(34.6+/-5.2) ml. The mean postoperative hospital
      stay was(7.2+/-3.6) days. Postoperative complication occurred in 6 patients(4 had
      enteritis and 2 had recurrent constipation) in whom 1 were considered as failure
      of TOSEPT because of redo-surgery or persistent problems in defecation. The
      remaining 53 patients had normal defecation pattern after(9.2+/-5.8) weeks of
      postoperative recovery period. Neonatal cases had significantly shorter operative
      time and postoperative hospital stay, and longer postoperative recovery period
      than non-neonatal cases(P<0.05). There were no significant differences in
      intraoperative blood loss and postoperative complication rate between the two
      groups(P>0.05). CONCLUSIONS: TOSEPT is effective and safe in the management of
      patients with Hirschsprung disease. However, a postoperative recovery period is
      required for a normal defecation pattern. Although neonatal cases have
      significantly shorter operative time and postoperative hospital stay than non
      neonatal cases, but longer postoperative recovery period should be consider when
      evaluating the outcome of TOSEPT.

PMID- 22851078
TI  - [Influence of interferon-alpha2a on thymidine phosphorylase expression and
      anticancer activity of 5'-deoxy-fluorouridine in human colon carcinoma cell lines
      LOVO and SW480].
AB  - OBJECTIVE: To detect the effect of interferon-alpha2a(IFN-alpha2a) on thymidine
      phosphorylase(TP) mRNA expression levels and the anticancer activity of 5
      fluorouracil(5-FU) and 5'-deoxy-fluorouridine(5'-DFUR) in human colon carcinoma
      cell lines LOVO and SW480. METHODS: Two human colon cancer cell lines LOVO and
      SW480 were cultured and treated with IFN-alpha2a at a series of dosage, and
      fluorescence quantitative PCR was carried out to detect the TP mRNA expression
      levels in these 2 cell lines. Then MTT assay and software Templet were used to
      determine the change of 50% inhibition concentration of 5-FU or 5'-DFUR combined
      with IFN-alpha2a on the two cell lines. RESULTS: The TP mRNA expressions were up
      regulated significantly by IFN-alpha2a at the doses of 500 U/ml and 5000 U/ml in
      LOVO(P<0.01). Compared with untreated cells(IFN-alpha2a 0 U/ml), no significance
      was found for TP mRNA expression levels in LOVO and SW480 treated by IFN-alpha2a
      at the dose of 50 U/ml (P>0.05). There was no significant difference for TP mRNA
      expression in SW480 between the dose of 0 U/ml and 500 U/ml of IFN
      alpha2a(P>0.05), while a significant increace was detected at the dose of 5000
      U/ml (P<0.01). No significant difference was found for the IC50 values after
      treatment of 5-FU combined with IFN-alpha2a (20 U/ml) on LOVO and SW480 compared
      with 5-FU alone, while the IC50 values after treatment of 5'-DFUR combined with
      IFN-alpha2a decreased significantly compared with 5'-DFUR alone(P<0.05).
      CONCLUSION: There is no direct inhibition effect of IFN-alpha2a on LOVO and SW480
      in vitro, while it can up-regulate TP mRNA expression levels both in LOVO and
      SW480, and enhance the anticancer effect of 5'-DFUR on these 2 cell lines.

PMID- 22851079
TI  - [Expression of microRNA-183 in stage II ( gastric cancer and its association with
      Ezrin protein].
AB  - OBJECTIVE: To investigate the expression of microRNA-183 (miR-183) and Ezrin
      protein in stage II( gastric cancer (GC). METHODS: Specimens of stage II( GC and
      paracancer tissues (5 cm away from the tumor tissues) were collected from 72
      patients. Real-time PCR was used to detect the miR-183 expression.
      Immunohistochemistry was used to examine the Ezrin protein expression in the
      tumor tissue. The associations of miR-183 expression with the clinicopathologic
      features of stage II( GC and Ezrin expression were analyzed. RESULTS: miR-183
      expression was lower in stage II( gastric cancer tissues compared with the
      paracancer tissues samples(median relative expression, 0.676 vs. 1.000, P<0.05).
      Low expression of miR-183 was significantly associated with histological
      differentiation(0.429 vs. 0.907, P<0.05), lymph node metastasis(0.507 vs. 0.908,
      P<0.05). The survival was shorter in patient with low expression of miR
      183(63.0+/-4.0) as compared to those with high expression of miR-183(75.2+/
      3.8)(P<0.05). There was a negative correlation between the expression of miR-183
      and Ezrin(r=-0.272, P<0.05). CONCLUSIONS: miR-183 is down-regulated in stage II(
      GC, and associated with the differentiation, metastasis, and prognosis. Ezrin is
      a potential regulatory protein of miR-183.

PMID- 22851080
TI  - [Construction of pGL3-hTERT-tk recombinant plasmid and effect of PEG
      PEI/Fe(3)0(4) Nano-magnetic fluid-tk/GCV on proliferation of gastric cancer cells
      BGC823 in vitro].
AB  - OBJECTIVE: To construct an hTERT promoter-controlled recombinant plasmid HSV-tk,
      and to investigate its expression in human gastric cancer cells BGC823 and its
      effect on proliferation of gastric cancer cells BGC823 in vitro. METHODS:
      Recombinant plasmid pGL3-hTERT-tk and the corresponding reporter plasmid pGL3
      hTERT-tk-Luc(+) were constructed by gene engineering. The recombinant plasmids
      were then transfected into gastric cancer cells BGC823 via PEG-PEI/Fe(3)0(4)
      magnetic nano-particles. Fluorescence microscope was used to observe the changes
      of cell morphology and the transfection efficiency. The expression of the target
      gene in gastric cancer cells BGC823 was detected by immunohistochemistry. MTT
      assay was used to evaluate the effect of HSV-tk on the proliferation of BGC823
      cells. Normal hepatic cells L02 were used as controls in all the experiments.
      RESULTS: Recombinant plasmid pGL3-hTERT-tk was successfully constructed, and the
      length was 1100 bp. pGL3-control-tk-Luc(+), pGL3-basic-tk-Luc(+) and pGL3-hTERT
      tk-Luc(+) all could effectively transfect BGC823 cells with high telomerase
      activity, with the transfection rate being(28.1+/-2.3)%. Immunohistochemistry
      study showed significant expression of HSV-tk gene in the cytoplasm of BGC823
      cells. MTT showed that 4 days after transfection of pGL3-hTERT-tk, the
      proliferation of BGC823 was inhibited, and the A570 value was(0.254+/-0.011),
      significantly lower than that of L02 cells(0.322+/-0.013) and that of BGC823
      transfected by pGL3-basic-tk (0.357+/-0.014)(all P<0.05). CONCLUSIONS: Magnetic
      nano-particles can transfect pGL3-hTERT-tk into BGC823 cells and the expression
      is achieved. PEG-PEI/Fe(3)0(4) magnetic nano-particles can significantly inhibit
      the proliferation of BGC823 and may become a potential biological agent for gene
      therapy of gastric cancer.

PMID- 22851081
TI  - [Association between gut-enriched Kruppel-like factor and prognosis of patients
      with gastric cancer].
AB  - OBJECTIVE: To explore the expression of gut-enriched  Kruppel-like factor 4(KLF4)
      in gastric cancer, and its association with prognosis. METHODS: Surgical
      specimens were collected from 264 patients undergoing radical surgery between
      2004 and 2009 in the Affiliated Qianfoshan Hospital, Shandong University. KLF4
      mRNA level of specimens was detected by real-time PCR. KLF4 protein expression
      was measured by immunohistochemistry on tissue microarray, which contained
      primary gastric cancer, corresponding para-cancerous tissue, and paired lymph
      node metastases. RESULTS: Real-time PCR revealed that mRNA level of KLF4 was down
      regulated in gastric cancer compared with paired normal gastric mucosa.
      Immunohistochemistry on tissue microarray showed gastric cancer tissues had
      significantly lower KLF4 levels compared with paired normal gastric tissues. By
      univariate and multivariate analysis, KLF4 was a significant predictor of
      survival and recurrence. CONCLUSION: KLF4 expression is significantly down
      regulated in gastric cancer, and is an independent predictor of survival and
      recurrence.

PMID- 22851082
TI  - [Association of SOX9 expression and prognosis in patients with gastric cancer].
AB  - OBJECTIVE: To investigate the association of SOX9 expression and
      clinicopathologic factors and prognosis of gastric cancer. METHODS: A
      retrospective cohort study including 112 gastric cancer patients admitted to the
      Zhejiang Provincial People's Hospital from 2004 to 2006 was performed.
      Immunohistochemical analysis was used to evaluate the expression of SOX9 in the
      112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to
      the tumor. RESULTS: Low expression of SOX9 was seen in 5(7.1%) tissues out of 70
      non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had
      varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate
      analysis demonstrated that the expression of SOX9 was significantly associated
      with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node
      metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however
      there was no significant association between SOX9 expression and sex, age,
      histological type, histology differentiation or tumor size. Kaplan-Meier analysis
      showed that the 5-year survival rate of patients with SOX9 over-expression was
      significantly lower than that of patients with low expression(29.4% vs. 49.2%,
      P=0.031). Multivariate Cox regression analysis showed that histology
      differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01)
      were independent prognostic factors for gastric cancer, however the over
      expression of SOX9 was not significant(P=0.948). CONCLUSIONS: The expression SOX9
      is associated with the growth, invasion, and metastasis of gastric cancer, as
      well as the prognosis. However, SOX9 expression is not an independent factor for
      the prognosis in patients with gastric cancer.

PMID- 22851083
TI  - [Hand-assisted laparoscopic radical gastrectomy: comparison between laparoscopic
      and open approach].
AB  - OBJECTIVE: To evaluate the short-term outcomes after hand-assisted laparoscopic
      radical gastrectomy. METHODS: Between June 2010 and May 2011, a series of 15
      patients underwent hand-assisted laparoscopic gastrectomy(HG), 16 patients
      underwent laparoscopic gastrectomy(LP), and 11 patients underwent open
      gastrectomy(OP). Short-term outcomes included operative time, blood loss, lymph
      nodes harvested, and the length of incision were collected after operation.
      RESULTS: The operative time was 150-200 min in HG, 180-220 min in LP, and 150-200
      min in OP respectively. The time of laparoscopic procedure was 18-58 and 70-100
      min respectively. The average incision length was 6.8 cm in HG, 5.6 cm in LP, and
      13.5 cm in OP. The average number of lymph nodes harvested was 17.6, 15.1 and
      16.4 respectively. The average estimated blood loss was 228 ml, 278 ml, and 427
      ml respectively. The mean length of hospital stay was 9.9, 10.8, and 12.4 d. No
      anastomotic leakage, bleeding, or gastric paralysis were found. One wound
      infection case was found in OP. CONCLUSIONS: Hand-assisted laparoscopic
      gastrectomy is in concordance with the standardized treatment protocol for
      gastric cancer. Lymph node dissection is easier by HG, therefore HG can be an
      alternative for the radical resection of gastric cancer.

PMID- 22851084
TI  - [Pathophysiology of slow transit constipation].
AB  - Slow transit constipation(STC)is the common type of chronic idiopathic
      constipation. Due to failure of routine conservative treatment, laxatives abuse
      is the most choice for majority of the patients, which could damage the enteric
      nervous system and result in aggravation of constipation. Resection of the slow
      transit colon is the ultimate option for some patients. It is hard to prevent and
      treat STC clinically because of the unknown pathophysiologic mechanism.
      Abnormalities of enteric neurotransmitters such as VIP, SP, NOS and decreased
      number of interstitial cells of Cajal have been described in the colon of the
      patients with STC. However, long term application of stimulant laxatives can also
      result in the almost same changes in the colon. Exploration of the potential
      relationship among the above reported abnormalities is the direction of future
      study.

PMID- 22851087
TI  - The cover. Flit.

PMID- 22851092
TI  - New research reveals positive therapies and methods for treating prostate cancer.

PMID- 22851093
TI  - WHO documents worldwide need for better drug abuse treatment--and access to it.

PMID- 22851094
TI  - Congenital Chagas disease reported in United States.

PMID- 22851099
TI  - Radiation therapy modalities for prostate cancer.

PMID- 22851100
TI  - Radiation therapy modalities for prostate cancer.

PMID- 22851101
TI  - Radiation therapy modalities for prostate cancer.

PMID- 22851103
TI  - Complementary health practices.

PMID- 22851104
TI  - Complementary health practices.

PMID- 22851106
TI  - Incomplete financial disclosure in a viewpoint on complementary and alternative
      therapies.

PMID- 22851107
TI  - Number and order of whole cell pertussis vaccines in infancy and disease
      protection.

PMID- 22851109
TI  - Curbing the opioid epidemic in the United States: the risk evaluation and
      mitigation strategy (REMS).

PMID- 22851110
TI  - Potential consequences of reforming Medicare into a competitive bidding system.

PMID- 22851111
TI  - Integrating public health and primary care systems: potential strategies from an
      IOM report.

PMID- 22851112
TI  - A piece of my mind. John Lennon's elbow.

PMID- 22851113
TI  - Effects of exercise training on depressive symptoms in patients with chronic
      heart failure: the HF-ACTION randomized trial.
AB  - CONTEXT: Depression is common in patients with cardiac disease, especially in
      patients with heart failure, and is associated with increased risk of adverse
      health outcomes. Some evidence suggests that aerobic exercise may reduce
      depressive symptoms, but to our knowledge the effects of exercise on depression
      in patients with heart failure have not been evaluated. OBJECTIVE: To determine
      whether exercise training will result in greater improvements in depressive
      symptoms compared with usual care among patients with heart failure. DESIGN,
      SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial involving
      2322 stable patients treated for heart failure at 82 medical clinical centers in
      the United States, Canada, and France. Patients who had a left ventricular
      ejection fraction of 35% or lower, had New York Heart Association class I to IV
      heart failure, and had completed the Beck Depression Inventory II (BDI-II) score
      were randomized (1:1) between April 2003 and February 2007. Depressive scores
      ranged from 0 to 59; scores of 14 or higher are considered clinically
      significant. INTERVENTIONS: Participants were randomized either to supervised
      aerobic exercise (goal of 90 min/wk for months 1-3 followed by home exercise with
      a goal of >=120 min/wk for months 4-12) or to education and usual guideline-based
      heart failure care. MAIN OUTCOME MEASURES: Composite of death or hospitalization
      due to any cause and scores on the BDI-II at months 3 and 12. RESULTS: Over a
      median follow-up period of 30 months, 789 patients (68%) died or were
      hospitalized in the usual care group compared with 759 (66%) in the aerobic
      exercise group (hazard ratio [HR], 0.89; 95% CI, 0.81 to 0.99; P = .03). The
      median BDI-II score at study entry was 8, with 28% of the sample having BDI-II
      scores of 14 or higher. Compared with usual care, aerobic exercise resulted in
      lower mean BDI-II scores at 3 months (aerobic exercise, 8.95; 95% CI, 8.61 to
      9.29 vs usual care, 9.70; 95% CI, 9.34 to 10.06; difference, -0.76; 95% CI,-1.22
      to -0.29; P = .002) and at 12 months (aerobic exercise, 8.86; 95% CI, 8.67 to
      9.24 vs usual care, 9.54; 95% CI, 9.15 to 9.92; difference, -0.68; 95% CI, -1.20
      to -0.16; P = .01). CONCLUSIONS: Compared with guideline-based usual care,
      exercise training resulted in a modest reduction in depressive symptoms, although
      the clinical significance of this improvement is unknown. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00047437.

PMID- 22851114
TI  - Association between endoscopic vs open vein-graft harvesting and mortality, wound
      complications, and cardiovascular events in patients undergoing CABG surgery.
AB  - CONTEXT: The safety and durability of endoscopic vein graft harvest in coronary
      artery bypass graft (CABG) surgery has recently been called into question.
      OBJECTIVE: To compare the long-term outcomes of endoscopic vs open vein-graft
      harvesting for Medicare patients undergoing CABG surgery in the United States.
      DESIGN, SETTING, AND PATIENTS: An observational study of 235,394 Medicare
      patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical
      centers participating in the Society of Thoracic Surgeons (STS) national
      database. The STS records were linked to Medicare files to allow longitudinal
      assessment (median 3-year follow-up) through December 31, 2008. MAIN OUTCOME
      MEASURES: All-cause mortality. Secondary outcome measures included wound
      complications and the composite of death, myocardial infarction, and
      revascularization. RESULTS: Based on Medicare Part B coding, 52% of patients
      received endoscopic vein-graft harvesting during CABG surgery. After propensity
      score adjustment for clinical characteristics, there were no significant
      differences between long-term mortality rates (13.2% [12,429 events] vs 13.4%
      [13,096 events]) and the composite of death, myocardial infarction, and
      revascularization (19.5% [18,419 events] vs 19.7% [19,232 events]). Time-to-event
      analysis for those patients receiving endoscopic vs open vein-graft harvesting
      revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality
      and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft
      harvesting was associated with lower harvest site wound complications relative to
      open vein-graft harvesting (3.0% [3654/122,899 events] vs 3.6% [4047/112,495
      events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001). CONCLUSION: Among
      patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting
      compared with open vein-graft harvesting was not associated with increased
      mortality.

PMID- 22851115
TI  - Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple
      colorectal adenomas.
AB  - CONTEXT: Patients with multiple colorectal adenomas may carry germline mutations
      in the APC or MUTYH genes. OBJECTIVES: To determine the prevalence of pathogenic
      APC and MUTYH mutations in patients with multiple colorectal adenomas who had
      undergone genetic testing and to compare the prevalence and clinical
      characteristics of APC and MUTYH mutation carriers. DESIGN, SETTING, AND
      PARTICIPANTS: Cross-sectional study conducted among 8676 individuals who had
      undergone full gene sequencing and large rearrangement analysis of the APC gene
      and targeted sequence analysis for the 2 most common MUTYH mutations (Y179C and
      G396D) between 2004 and 2011. Individuals with either mutation underwent full
      MUTYH gene sequencing. APC and MUTYH mutation prevalence was evaluated by polyp
      burden; the clinical characteristics associated with a pathogenic mutation were
      evaluated using logistic regression analyses. MAIN OUTCOME MEASURE: Prevalence of
      pathogenic mutations in APC and MUTYH genes. RESULTS: Colorectal adenomas were
      reported in 7225 individuals; 1457 with classic polyposis (>=100 adenomas) and
      3253 with attenuated polyposis (20-99 adenomas). The prevalence of pathogenic APC
      and biallelic MUTYH mutations was 95 of 119 (80% [95% CI, 71%-87%]) and 2 of 119
      (2% [95% CI, 0.2%-6%]), respectively, among individuals with 1000 or more
      adenomas, 756 of 1338 (56% [95% CI, 54%-59%]) and 94 of 1338 (7% [95% CI, 6%-8%])
      among those with 100 to 999 adenomas, 326 of 3253 (10% [95% CI, 9%-11%]) and 233
      of 3253 (7% [95% CI, 6%-8%]) among those with 20 to 99 adenomas, and 50 of 970
      (5% [95% CI, 4%-7%]) and 37 of 970 (4% [95% CI, 3%-5%]) among those with 10 to 19
      adenomas. Adenoma count was strongly associated with a pathogenic mutation in
      multivariable analyses. CONCLUSIONS: Among patients with multiple colorectal
      adenomas, pathogenic APC and MUTYH mutation prevalence varied considerably by
      adenoma count, including within those with a classic polyposis phenotype. APC
      mutations predominated in patients with classic polyposis, whereas prevalence of
      APC and MUTYH mutations was similar in attenuated polyposis. These findings
      require external validation.

PMID- 22851116
TI  - Risk of fractures following cataract surgery in Medicare beneficiaries.
AB  - CONTEXT: Visual impairment is a known risk factor for fractures. Little is known
      about the association of cataract surgery with fracture risk. OBJECTIVE: To
      determine the association of cataract surgery with subsequent fracture risk in US
      Medicare beneficiaries with a diagnosis of cataract. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective study of 1-year fracture incidence in a 5% random
      sample of Medicare Part B beneficiaries with cataract who received and did not
      receive cataract surgery from 2002 through 2009. MAIN OUTCOME MEASURES: One-year
      incidence of hip fractures. Analyses were adjusted for age; sex; race/ethnicity;
      US region of residence; systemic comorbidities, including Charlson Comorbidity
      Index (CCI) score; ocular comorbidities; cataract severity; and presence of
      physically limiting conditions. Adjusted odds ratios (ORs) of hip fractures were
      calculated using logistic regression modeling. RESULTS: There were 1,113,640 US
      Medicare beneficiaries 65 years and older with a diagnosis of cataract between
      2002 and 2009 in the 5% random sample; of these patients, 410,809 (36.9%)
      received cataract surgery during the study period. There were 13,976 patients
      (1.3%) who sustained a hip fracture during the study period. The most common
      fracture-related comorbidity was osteoporosis (n = 134,335; 12.1%). The most
      common ocular comorbidity was glaucoma (n = 212,382; 19.1%). Compared with 1-year
      hip fracture incidence in patients with cataract who did not have cataract
      surgery, adjusted OR of hip fracture within 1 year after cataract surgery was
      0.84 (95% CI, 0.81-0.87) with an absolute risk difference of 0.20%. Compared with
      matched subgroups of patients who did not receive cataract surgery, patient
      subgroups that experienced lower odds of hip fracture after cataract surgery
      included patients with severe cataract, patients most likely to receive cataract
      surgery based on propensity score, patients 75 years and older, and patients with
      a CCI score of 3 or greater. CONCLUSION: In a cohort of US Medicare beneficiaries
      aged 65 years and older with a diagnosis of cataract, patients who had cataract
      surgery had lower odds of hip fracture within 1 year after surgery compared with
      patients who had not undergone cataract surgery.

PMID- 22851117
TI  - Does this adult patient with suspected bacteremia require blood cultures?
AB  - CONTEXT: Clinicians order blood cultures liberally among patients in whom
      bacteremia is suspected, though a small proportion of blood cultures yield true
      positive results. Ordering blood cultures inappropriately may be both wasteful
      and harmful. OBJECTIVE: To review the accuracy of easily obtained clinical and
      laboratory findings to inform the decision to obtain blood cultures in suspected
      bacteremia. DATA SOURCES AND STUDY SELECTION: A MEDLINE and EMBASE search
      (inception to April 2012) yielded 35 studies that met inclusion criteria for
      evaluating the accuracy of clinical variables for bacteremia in adult
      immunocompetent patients, representing 4566 bacteremia and 25,946 negative blood
      culture episodes. DATA EXTRACTION: Data were extracted to determine the
      prevalence and likelihood ratios (LRs) of findings for bacteremia. DATA
      SYNTHESIS: The pretest probability of bacteremia varies depending on the clinical
      context, from low (eg, cellulitis: 2%) to high (eg, septic shock: 69%). Elevated
      temperatures alone do not accurately predict bacteremia (for >=38 degrees C
      [>100.3 degrees F], LR, 1.9 [95% CI, 1.4-2.4]; for >=38.5 degrees C [>101.2
      degrees F], LR, 1.4 [95% CI, 1.1-2.0]), nor does isolated leukocytosis (LR,
      <1.7). The severity of chills graded on an ordinal scale (shaking chills, LR,
      4.7; 95% CI, 3.0-7.2) may be more useful. Both the systemic inflammatory response
      syndrome (SIRS) and a multivariable decision rule with major and minor criteria
      are sensitive (but not specific) predictors of bacteremia (SIRS, negative LR,
      0.09 [95% CI, 0.03-0.26]; decision rule, negative LR, 0.08 [95% CI, 0.04-0.17]).
      CONCLUSIONS: Blood cultures should not be ordered for adult patients with
      isolated fever or leukocytosis without considering the pretest probability. SIRS
      and the decision rule may be helpful in identifying patients who do not need
      blood cultures. These conclusions do not apply to immunocompromised patients or
      when endocarditis is suspected.

PMID- 22851118
TI  - Endoscopic vein-graft harvest is safe for CABG surgery.

PMID- 22851119
TI  - APC gene testing for familial adenomatosis polyposis.

PMID- 22851123
TI  - JAMA patient page. Viral gastroenteritis.

PMID- 22851124
TI  - The effect of femoral component rotation on the five-year outcome of cemented
      mobile bearing total knee arthroplasty.
AB  - PURPOSE: Performing total knee replacement, accurate alignment and neutral
      rotation of the femoral component are widely believed to be crucial for the
      ultimate success. Contrary to absolute bone referenced alignment, using a
      ligament balancing technique does not automatically rotate the femoral component
      parallel to the transepicondylar axis. In this context we established the
      hypothesis that rotational alignment of the femoral component parallel to the
      transepicondylar axis (0 degrees  +/- 3 degrees ) results in better outcome than
      alignment outside of this range. METHODS: We analysed 204 primary cemented mobile
      bearing total knee replacements five years postoperatively. Femoral component
      rotation was measured on axial radiographs using the condylar twist angle (CTA).
      Knee society score, range of motion as well as subjective rating documented
      outcome. RESULTS: In 96 knees the femoral component rotation was within the range
      0 +/- 3 degrees  (neutral rotation group), and in 108 knees the five-year
      postoperative rotational alignment of the femoral component was outside of this
      range (outlier group). Postoperative CTA showed a mean of 2.8 degrees  (+/-3.4
      degrees ) internal rotation (IR) with a range between 6 degrees  external
      rotation (ER) and 15 degrees  IR (CI 95). No difference with regard to subjective
      and objective outcome could be detected. CONCLUSION: The present work shows that
      there is a large given natural variability in optimal rotational orientation, in
      this study between 6 degrees  ER and 15 degrees  IR, with numerous co-factors
      determining correct positioning of the femoral component. Further studies
      substantiating pre- and postoperative determinants are required to complete the
      understanding of resulting biomechanics in primary TKA.

PMID- 22851125
TI  - Iatrogenic popliteus tendon injury during total knee arthroplasty results in
      decreased knee function two to three years postoperatively.
AB  - PURPOSE: The popliteus tendon is known to play a key role in the stability of the
      posterolateral corner of the knee. While prior work suggests that isolated
      sectioning of the popliteus tendon has little consequence for the static
      stability of the knee following TKA, no studies have evaluated the effect of
      iatrogenic popliteal tendon injury on patient oriented outcome and knee function
      following TKA. The aims of this study are (1) to compare patient-oriented outcome
      scores of patients who suffered an iatrogenic injury to the popliteus tendon with
      a control group without such an injury and (2) to identify risk factors
      associated with iatrogenic injury to the popliteus tendon. METHODS: Fifteen
      patients with an iatrogenic complete transection of the popliteus tendon during
      TKA were compared to the 666 patients who underwent TKA during the same time
      period without popliteus tendon injury. RESULTS: Postoperatively, IKS knee scores
      were similar between the two groups; however, significantly lower IKS function
      scores were noted in the study group (71 +/- 31) compared to the control group
      (86 +/- 19) (p = 0.0036). Iatrogenic popliteal tendon injury was only noted to
      occur in patients in whom components of size four or smaller were used.
      CONCLUSIONS: Intraoperative complete section of the popliteus tendon during the
      performance of TKA results in decreased IKS functional scores two to three years
      postoperatively. Patients with smaller knees may be at higher risk for this
      complication.

PMID- 22851127
TI  - Adding propranolol to topiramate is innefective in chronic migraine: in search of
      a better combination therapy for chronic migraine.

PMID- 22851126
TI  - Coupled dynamics of energy budget and population growth of tilapia in response to
      pulsed waterborne copper.
AB  - The impact of environmentally pulsed metal exposure on population dynamics of
      aquatic organisms remains poorly understood and highly unpredictable. The purpose
      of our study was to link a dynamic energy budget model to a
      toxicokinetic/toxicodynamic (TK/TD). We used the model to investigate tilapia
      population dynamics in response to pulsed waterborne copper (Cu) assessed with
      available empirical data. We mechanistically linked the acute and chronic
      bioassays of pulsed waterborne Cu at the scale of individuals to tilapia
      populations to capture the interaction between environment and population growth
      and reproduction. A three-stage matrix population model of larva-juvenile-adult
      was used to project offspring production through two generations. The estimated
      median population growth rate (lambda) decreased from 1.0419 to 0.9991 under
      pulsed Cu activities ranging from 1.6 to 2.0 MUg L(-1). Our results revealed that
      the influence on lambda was predominately due to changes in the adult survival
      and larval survival and growth functions. We found that pulsed timing has
      potential impacts on physiological responses and population abundance. Our study
      indicated that increasing time intervals between first and second pulses
      decreased mortality and growth inhibition of tilapia populations, indicating that
      during long pulsed intervals tilapia may have enough time to recover. Our study
      concluded that the bioenergetics-based matrix population methodology could be
      employed in a life-cycle toxicity assessment framework to explore the effect of
      stage-specific mode-of-actions in population response to pulsed contaminants.

PMID- 22851128
TI  - Measuring perinatal mental health risk.
AB  - The purpose of this review was to critically analyse existing tools to measure
      perinatal mental health risk and report on the psychometric properties of the
      various approaches using defined criteria. An initial literature search revealed
      379 papers, from which 21 papers relating to ten instruments were included in the
      final review. A further four papers were identified from experts (one excluded)
      in the field. The psychometric properties of six multidimensional tools and/or
      criteria were assessed. None of the instruments met all of the requirements of
      the psychometric properties defined. Some had used large sample sizes but
      reported low positive predictive values (Antenatal Risk Questionnaire (ANRQ)) or
      insufficient information regarding their clinical performance (Antenatal Routine
      Psychosocial Assessment (ARPA)), while others had insufficient sample sizes
      (Antenatal Psychosocial Health Assessment Tool, Camberwell Assessment of Need
      Mothers and Contextual Assessment of Maternity Experience). The ANRQ has
      fulfilled the requirements of this analysis more comprehensively than any other
      instrument examined based on the defined rating criteria. While it is desirable
      to recommend a tool for clinical practice, it is important that clinicians are
      made aware of their limitations. The ANRQ and ARPA represent multidimensional
      instruments commonly used within Australia, developed within large samples with
      either cutoff scores or numbers of risk factors related to service outcomes.
      Clinicians can use these tools, within the limitations presented here, to
      determine the need for further intervention or to refer women to mental health
      services. However, the effectiveness of routine perinatal psychosocial assessment
      continues to be debated, with further research required.

PMID- 22851129
TI  - Cathepsin B SNPs elevate the pathological development of oral cancer and raise
      the susceptibility to carcinogen-mediated oral cancer.
AB  - Oral cancer is causally associated with environmental carcinogens, and the
      susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype
      dependent. Cathepsin B (CTSB) is a lysosomal cysteine protease and may serve as a
      candidate biomarker of oral cancer. The current study aimed to explore the
      influences of three single nucleotide polymorphisms (SNPs) in CTSB gene, combined
      with environmental carcinogens on the risk and clinicopathological development of
      oral cancer. Three SNPs of CTSB, CTSB C76G (rs12338), CTSB A4383C (rs13332), and
      CTSB A8422G (rs8898), from 444 male patients with oral cancer and 426 control
      participants (males not diagnosed with cancer) in Taiwan were analyzed. These
      three CTSB SNPs all exhibited insignificant (P > 0.05) effects on the risk of
      oral cancer. However, the risk for developing the poor clinical stage of
      moderately or poorly differentiated cells was significantly (P < 0.001) increased
      to 3.325-fold in patients with oral cancer carrying the polymorphic genotype of
      rs8898 compared to patients with the ancestral genotype. Additionally, while
      considering the exposure of environmental carcinogens, the presence of these
      three CTSB SNPs, combined with betel quid chewing [adjusted odds ratio (AOR) was
      36.570, 21.772, and 43.962 for rs12338, rs13332, and rs8898, respectively] and/or
      tobacco use (AOR was 3.794, and 8.972 for rs12338 and rs13332, respectively),
      robustly elevated the susceptibility to oral cancer. These results suggest that
      the genetic polymorphism of CTSB A8422G (rs8898) was associated with a high risk
      for the clinicopathological development of oral cancer and CTSB gene
      polymorphisms may increase the susceptibility to environmental carcinogens
      mediated oral cancer.

PMID- 22851130
TI  - Synthetic lethal interactions in yeast reveal functional roles of J protein co
      chaperones.
AB  - J proteins are a diverse family of co-chaperones that cooperate with heat shock
      protein 70 (Hsp70) to coordinate protein quality control, especially in response
      to cellular stress. Current models suggest that individual J proteins might play
      roles in recruiting Hsp70s to specific functions, such as maintaining cell wall
      integrity or promoting ribosome biogenesis. However, relatively few stresses have
      been used to test this model and, as a result, only a few specific activities
      have been identified. To expand our understanding of the J protein network, we
      used a synthetic lethal approach in which 11 Saccharomyces cerevisiae deletion
      strains were treated with 12 well-characterized chemical inhibitors. The results
      defined new roles for specific J proteins in major signaling pathways. For
      example, an important role for Swa2 in cell wall integrity was identified and
      activities of the under-explored Jjj1, Apj1, Jjj3 and Caj1 proteins were
      suggested. More generally, these findings support a model in which some J
      proteins, such as Ydj1 and Zuo1, play "generalist" roles, while others, such as
      Apj1 and Jjj2, are "specialists", having roles in relatively few pathways.
      Together, these results provide new insight into the network of J proteins.

PMID- 22851131
TI  - Religious participation and DSM IV major depressive disorder among Black
      Caribbeans in the United States.
AB  - This study examines the relationship between religious involvement and 12-month
      and lifetime DSM-IV major depressive disorder (MDD) within a nationally
      representative sample of Black Caribbean adults. MDD was assessed using the DSM
      IV World Mental Health Composite International Diagnostic Interview (WMH-CIDI).
      Religious involvement included measures of religious coping, organizational and
      nonorganizational involvement, and subjective religiosity. Study findings
      indicate that religious involvement is associated with 12-month and lifetime
      prevalence of MDD. Multivariate relationships between religious involvement and
      MDD indicate lower prevalence of 12-month and lifetime MDD among persons who use
      religious coping and characterize themselves as being religious (for lifetime
      prevalence only); persons who frequently listen to religious radio programs
      report higher lifetime MDD. Lower rates of 12-month and lifetime MDD are noted
      for persons who attend religious services at least once a week (as compared to
      both higher and lower levels of attendance), indicating a curvilinear
      relationship. The findings are discussed in relation to previous research on
      religion and mental health concerns, conceptual models of the role of religion in
      mental health (e.g., prevention, resource mobilization) that specify multiple and
      often divergent pathways and mechanisms of religious effects on health outcomes,
      and the role of religion among Caribbean Blacks. 

PMID- 22851132
TI  - Individual, household and administrative area levels of social capital and their
      associations with mental health: a multi-level analysis of cross-sectional
      evidence.
AB  - BACKGROUND: Research has seldom considered social capital at the individual,
      household and administrative area level simultaneously and examined its
      association with mental health. AIM: The main purpose of this study was to
      examine the association between social capital and mental health while
      controlling for various confounders at multiple levels using multi-level analysis
      and operationalizing social capital at the individual, household and
      administrative area level. METHODS: This study used cross-sectional data from the
      2010 Seoul Welfare Panel Study conducted by the Seoul Welfare Foundation
      (participation rates for the household and household members were 87.6% and
      87.5%, respectively). RESULTS: and conclusions: The main finding of this study
      was that organizational participation (B = 0.132, p < .001) and perceived
      helpfulness (B = 0.129, p < .001) were positively associated with mental health.
      This study also found that perceived helpfulness was positively associated with
      mental health (B = 0.070, p < .001). However, it did not find a significant
      association between the contextual level of social capital and mental health. The
      results indicate that the different dimensions of social capital may act
      differently to mental health depending on the level.

PMID- 22851133
TI  - Social relationships and postpartum depression in South Asia: a systematic
      review.
AB  - BACKGROUND: Evidence suggests a much higher prevalence of postpartum depression
      in South Asia than in 'western' contexts. AIM: To conduct a rapid systematic
      review of evidence on the association between social relationships and postpartum
      depression in South Asia. METHODS: Five databases were searched to identify
      relevant studies. Studies meeting the selection and quality criteria were
      analysed and integrated in a narrative review. RESULTS: Nine mostly quantitative
      studies were included in the review. Low support and poor relationships with the
      husband and parents-in-law were associated with postpartum depression, although
      associations were weakened in multivariate analyses. The different dimensions of
      support have not yet been systematically investigated and the likely complex
      interrelationships between social relationship risk factors are not yet well
      understood. CONCLUSIONS: Findings mirror those from 'western' contexts, showing
      the key role of social relationships in the aetiology of postpartum depression.
      Yet, they also reinforce the hypothesis that the social and cultural context
      influences the association. The importance of relationships with the extended
      family, as well as the husband, in South Asia is highlighted. Further research is
      recommended to develop an understanding of these relationships to better inform
      interventions.

PMID- 22851134
TI  - Prevalence and predictors of stress disorders following two earthquakes.
AB  - BACKGROUND: Studies about stress disorders following a disaster have mainly been
      based on single-event trauma with little emphasis on multiple traumas. AIMS: This
      study investigated the prevalence and predictors of stress disorders following
      two earthquakes in China. METHODS: Subjects were randomly sampled from 11
      villages in rural China. A total of 624 subjects were administered with the 12
      item General Health Questionnaire (GHQ-12), Symptom Checklist -90-R (SCL-90-R),
      Coping Style Scale and Social Support Rating Scale. This was followed by a
      structural clinical interview using the Chinese translation of the Structured
      Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV-TR axis 1
      disorders (SCID-I-P) for acute stress disorder (ASD) and post-traumatic stress
      disorder (PTSD). RESULTS: The prevalence of ASD and PTSD was 15% and 29%,
      respectively. Regression analysis indicated that high intensity of trauma
      exposure, lower educational level, subjective feeling of economic status and
      psychological stress after the first earthquake significantly predicted the
      outcome of PTSD. CONCLUSIONS: The study suggested that the prevalence of stress
      disorders in two earthquakes were higher than that experienced in a single
      disaster. The intensity of trauma exposure, low educational level, bad subjective
      feeling of economic status, and psychological stress after the first earthquake
      could be used to identify survivors at risk of developing PTSD in two
      earthquakes.

PMID- 22851135
TI  - The impact of spirituality on eating disorder symptomatology in ethnically
      diverse Canadian women.
AB  - BACKGROUND: There is currently a gap in our knowledge of how eating disorder
      symptomatology is impacted by spirituality and religiosity. To date, studies
      examining the role of ethnicity in women's self-reported levels of eating
      disorder symptomatology have neglected the roles of spirituality and religiosity.
      AIMS: This study addresses this gap in the literature by investigating ethnicity,
      spirituality, religiosity, body shame, body mass index (BMI) and age in relation
      to eating disorder symptomatology in women. METHODS: A representative non
      clinical sample of ethnically diverse Canadian women (N = 591) was surveyed.
      RESULTS: Younger women, particularly those with higher body shame, BMI and lower
      spirituality, reported more eating disorder symptomatology. Hispanic and Asian
      women had higher body shame and lower BMI compared to white women. Spirituality
      was more strongly related to eating disorder symptomatology than religiosity.
      CONCLUSIONS: This is the first study identifying interactive relationships
      between ethnicity, spirituality, body shame, BMI and age on eating disorder
      symptomatology in women. Particularly significant is that higher spirituality was
      related to a lower level of eating disorder symptomatology. These findings have
      important implications for treatment and women's physical and psychological
      health and wellness.

PMID- 22851136
TI  - Temperature-induced changes of HtrA2(Omi) protease activity and structure.
AB  - HtrA2(Omi), belonging to the high-temperature requirement A (HtrA) family of
      stress proteins, is involved in the maintenance of mitochondrial homeostasis and
      in the stimulation of apoptosis, as well as in cancer and neurodegenerative
      disorders. The protein comprises a serine protease domain and a postsynaptic
      density of 95 kDa, disk large, and zonula occludens 1 (PDZ) regulatory domain and
      functions both as a protease and a chaperone. Based on the crystal structure of
      the HtrA2 inactive trimer, it has been proposed that PDZ domains restrict
      substrate access to the protease domain and that during protease activation there
      is a significant conformational change at the PDZ-protease interface, which
      removes the inhibitory effect of PDZ from the active site. The crystal structure
      of the HtrA2 active form is not available yet. HtrA2 activity markedly increases
      with temperature. To understand the molecular basis of this increase in activity,
      we monitored the temperature-induced structural changes using a set of single-Trp
      HtrA2 mutants with Trps located at the PDZ-protease interface. The accessibility
      of each Trp to aqueous medium was assessed by fluorescence quenching, and these
      results, in combination with mean fluorescence lifetimes and wavelength emission
      maxima, indicate that upon an increase in temperature the HtrA2 structure
      relaxes, the PDZ-protease interface becomes more exposed to the solvent, and
      significant conformational changes involving both domains occur at and above 30 
      degrees C. This conclusion correlates well with temperature-dependent changes of
      HtrA2 proteolytic activity and the effect of amino acid substitutions (V226K and
      R432L) located at the domain interface, on HtrA2 activity. Our results
      experimentally support the model of HtrA2 activation and provide an insight into
      the mechanism of temperature-induced changes in HtrA2 structure.

PMID- 22851137
TI  - Extracellular HSP27 acts as a signaling molecule to activate NF-kappaB in
      macrophages.
AB  - Heat shock protein 27 (HSP27) shows attenuated expression in human coronary
      arteries as the extent of atherosclerosis progresses. In mice, overexpression of
      HSP27 reduces atherogenesis, yet the precise mechanism(s) are incompletely
      understood. Inflammation plays a central role in atherogenesis, and of particular
      interest is the balance of pro- and anti-inflammatory factors produced by
      macrophages. As nuclear factor-kappa B (NF-kappaB) is a key immune signaling
      modulator in atherogenesis, and macrophages are known to secrete HSP27, we sought
      to determine if recombinant HSP27 (rHSP27) alters NF-kappaB signaling in
      macrophages. Treatment of THP-1 macrophages with rHSP27 resulted in the
      degradation of an inhibitor of NF-kappaB, IkappaBalpha, nuclear translocation of
      the NF-kappaB p65 subunit, and increased NF-kappaB transcriptional activity.
      Treatment of THP-1 macrophages with rHSP27 yielded increased expression of a
      variety of genes, including the pro-inflammatory factors, IL-1beta, and TNF
      alpha. However, rHSP27 also increased the expression of the anti-inflammatory
      factors IL-10 and GM-CSF both at the mRNA and protein levels. Our study suggests
      that in macrophages, activation of NF-kappaB signaling by rHSP27 is associated
      with upregulated expression and secretion of key pro- and anti-inflammatory
      cytokines. Moreover, we surmise that it is the balance in expression of these
      mediators and antagonists of inflammation, and hence atherogenesis, that yields a
      favorable net effect of HSP27 on the vessel wall.

PMID- 22851138
TI  - Probing the transient interaction between the small heat-shock protein Hsp21 and
      a model substrate protein using crosslinking mass spectrometry.
AB  - Small heat-shock protein chaperones are important players in the protein quality
      control system of the cell, because they can immediately respond to partially
      unfolded proteins, thereby protecting the cell from harmful aggregates. The small
      heat-shock proteins can form large polydisperse oligomers that are exceptionally
      dynamic, which is implicated in their function of protecting substrate proteins
      from aggregation. Yet the mechanism of substrate recognition remains poorly
      understood, and little is known about what parts of the small heat-shock proteins
      interact with substrates and what parts of a partially unfolded substrate protein
      interact with the small heat-shock proteins. The transient nature of the
      interactions that prevent substrate aggregation rationalize probing this
      interaction by crosslinking mass spectrometry. Here, we used a workflow with
      lysine-specific crosslinking and offline nano-liquid chromatography matrix
      assisted laser desorption/ionization tandem time-of-flight mass spectrometry to
      explore the interaction between the plant small heat-shock protein Hsp21 and a
      thermosensitive model substrate protein, malate dehydrogenase. The identified
      crosslinks point at an interaction between the disordered N-terminal region of
      Hsp21 and the C-terminal presumably unfolding part of the substrate protein.

PMID- 22851140
TI  - Notch1 activation in embryonic VE-cadherin populations selectively blocks
      hematopoietic stem cell generation and fetal liver hematopoiesis.
AB  - Hematopoietic stem cells (HSC) are found in several independent sites
      embryonically. Loss-of-function studies indicated that Notch1, but not Notch2
      signaling was required for HSC emergence from the aortic-gonado-mesonephros (AGM)
      region. We previously showed that constitutive Notch1 activation impaired
      primitive erythroid differentiation, but its effects on HSC emergence from the
      AGM region were not studied. To further define specific roles of Notch receptors,
      we characterized HSC in mouse embryos expressing either Notch1 intracellular
      domain (ICD) or Notch4ICD in VE-cadherin or SM22alpha expressing populations.
      Although embryonic Notch1 activation in VE-cadherin populations led to lethality
      after E13.5, earlier defects in the fetal liver were observed. Embryos were
      analyzed at E12.5 to assess hematopoiesis and the phenotype of developing cells
      in the AGM region. We found that activation of Notch1 in the endothelial
      compartment in VE-cadherin expressing cells resulted in the absence of intra
      aortic clusters and defects in fetal liver hematopoiesis. In contrast, although
      Notch4 expression is regulated during fetal hematopoiesis, activation of Notch4
      in VE-cadherin expressing populations did not affect HSC phenotype, although
      later vascular remodeling was impaired. Likewise, activation of Notch1 in
      SM22alpha positive populations had no significant effect on hematopoiesis. Our
      results indicate a cell type-dependent activity and distinct features of Notch1
      versus Notch4 signaling and their impact on HSC generation.

PMID- 22851142
TI  - Role of intraoperative cholangiography in patients whose biliary tree was
      evaluated preoperatively by magnetic resonance cholangiopancreatography.
AB  - BACKGROUND: Routine performance of intraoperative cholangiography (IOC) during
      cholecystectomy is controversial. The aim of this study was to evaluate the role
      of IOC during cholecystectomy in addition to preoperative magnetic resonance
      cholangiopancreatography (MRCP) in our institution over a 12-year period.
      METHODS: A total of 425 consecutive patients who underwent IOC during
      cholecystectomy were included in this study. MRCP was performed preoperatively
      for bile duct evaluation in all patients. When common bile duct (CBD) stones were
      detected, they were removed endoscopically before the operation. We estimated the
      results of IOC in terms of the success rate, the detection rate of anatomic
      abnormality of the biliary system, and the incidence of residual CBD stones.
      RESULTS: MRCP preoperatively identified 6 (1.4 %) patients with abnormal biliary
      systems and 56 with CBD stones, which were endoscopically removed. The success
      rate of IOC was 93.8 % (399/425). Abnormalities of the biliary system were
      detected in 12 patients (12/399, 3.0 %) and CBD stones in 8 (8/399, 2.0 %). Of
      the eight patients with stones, seven had been examined by endoscopy
      preoperatively and found to have CBD stones. The detection rate of bile duct
      stones in patients with preoperative endoscopic removal of CBD stones (7/56, 12.5
      %) was significantly higher than those with CBD stones first detected during IOC
      (1/365, 0.3 %) (p < 0.01). Moreover, no residual CBD stones were detected in
      patients who were operated on within fewer than 12 days from endoscopic treatment
      to the operation. CONCLUSIONS: IOC is indicated even after preoperative
      sphincterotomy for CBD stones. In our study, it resulted in a 12.5 % incidence of
      persistent stones after sphincterotomy. IOC plays an additional role in detecting
      CBD stones and in revealing abnormalities of the biliary tree in patients whose
      biliary tree was preoperatively evaluated by MRCP.

PMID- 22851143
TI  - Routine chest X-ray prior to thyroid surgery: is it always necessary?
AB  - BACKGROUND: Despite lack of evidence-based support, chest X-ray (CXR) prior to
      thyroid surgery is often used to identify tracheal deviation that may predict
      difficulty with intubation. The aim of this study is to establish the utility of
      preoperative CXR to assess tracheal deviation in this group of patients. METHODS:
      We analyzed a prospective database of 1,000 consecutive patients who underwent
      thyroid surgery. Patients' charts were reviewed for demographic data, CXR
      readings, other imaging findings, anesthesia records, and pathology findings.
      Patients with tracheal deviation (TD) on CXR were compared to patients without
      (no TD). RESULTS: Six hundred eighty-nine (69 %) patients had a CXR performed
      prior to surgery. TD was identified in 252 (37 %) patients while 437 (63 %) did
      not have TD. The two groups did not significantly differ in mean age, BMI, or
      gender. Patients with TD on CXR had larger thyroid glands (51 +/- 4 vs. 28 +/- 2
      g, p < 0.001) and reported a higher rate of tracheal compressive symptoms (19 vs.
      12 %, p = 0.005). However, this did not translate into more difficult intubations
      as reported by the anesthesiologist (5 vs. 7 %, p = 0.31) or more intubation
      attempts (1.2 +/- 0 vs. 1.1 +/- 0, p = 0.1). Lung findings on CXR that resulted
      in further workup were identified in 32 (5 %) patients, with additional pathology
      found in only 6 (1 %) patients. CONCLUSION: There is no correlation between a
      finding of tracheal deviation on preoperative CXR and difficult intubation in
      thyroid patients. Therefore, CXR for the sole purpose of identifying tracheal
      deviation in thyroid surgery candidates is not warranted.

PMID- 22851141
TI  - Prognostic microRNAs in cancer tissue from patients operated for pancreatic
      cancer--five microRNAs in a prognostic index.
AB  - BACKGROUND: The aim of the present study was to identify a panel of microRNAs
      (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer
      tissues from patients operated for pancreatic cancer (PC). METHODS: MiRNAs were
      purified from formalin-fixed paraffin embedded (FFPE) cancer tissue from 225
      patients operated for PC. Only a few of those patients received adjuvant
      chemotherapy. Expressions of miRNAs were determined with the TaqMan MicroRNA
      Array v2.0. Two statistical methods, univariate selection and the Lasso (Least
      Absolute Shrinkage and Selection Operator) method, were applied in conjunction
      with the Cox proportional hazard model to relate miRNAs to OS. RESULTS: High
      expression of miR-212 and miR-675 and low expression of miR-148a, miR-187, and
      let-7g predicted short OS independent of age, gender, calendar year of operation,
      KRAS mutation status, tumor stage, American Society of Anesthesiologists (ASA)
      score, localization (not miR-148a), and differentiation of tumor. A prognostic
      index (PI) based on these five miRNAs was calculated for each patient. The median
      survival was 1.09 years (Confidence Interval [CI] 0.98-1.43) for PI > median PI
      compared to 2.23 years (CI 1.84-4.36) for PI < median. MiR-212, miR-675, miR-187,
      miR-205, miR-944, miR-431, miR-194, miR-148a, and miR-769-5p showed the strongest
      prediction ability by the Lasso method. Thus miR-212, miR-675, miR-187, and miR
      148a were predictors for OS in both statistical methods. CONCLUSIONS: The
      combination of five miRNAs expression in non micro-dissected FFPE PC tissue can
      identify patients with short OS after radical surgery. The results are
      independent of chemotherapy treatment. Patients with a prognostic index > median
      had a very short median OS of only 1 year.

PMID- 22851144
TI  - Long-term outcomes following aggressive management of recurrent hepatocellular
      carcinoma after upfront liver resection.
AB  - BACKGROUND: Long-term outcomes of patients who experience recurrence after liver
      resection (LR) of hepatocellular carcinoma (HCC) are uncertain. METHODS: The
      characteristics of 58 patients were obtained from a retrospective database at two
      time points: primary resection and recurrence. Patterns of recurrence, treatment
      strategies, and long-term survival rates were analyzed. RESULTS: The recurrence
      was inside the Milan criteria (Milan+) in 19 patients (32.7 %), 11 of whom were
      already eligible for a liver transplant (LT) at the time of primary liver
      resection (LR). Treatment of the recurrence included the following procedures:
      salvage LT (n = 6; 10.3 %), repeat LR (n = 7; 12.1 %), percutaneous
      radiofrequency ablation (RFA) and/or transarterial chemoembolization (TACE) (n =
      24; 41.3 %), systemic chemotherapy (n = 15; 25.8 %), and best supportive care (n
      = 12; 20.7 %). With a mean follow-up of 26.9 +/- 27.9 months, the overall 1-, 3-,
      and 5-year survival rates of the 58 patients with HCC recurrence after primary LR
      were 57.3, 42.5, and 35.3 %, respectively. In the multivariate analysis the
      presence of esophageal varices (p = 0.001), an AFP level >200 MUg/L (p = 0.03)
      and a Milan- recurrence pattern (p = 0.05) were independent predictors of
      decreased survival. The overall 5-year survival of patients who experienced
      Milan+ recurrence was comparable to that of Milan+ patients who underwent primary
      LR (62.5 % vs. 66.3 %, p = 0.48). CONCLUSIONS: Aggressive management of recurrent
      HCC after upfront LR improves patient survival. The pattern of recurrence is an
      independent predictor of survival which can be used as a selection criterion for
      salvage LT.

PMID- 22851145
TI  - Mortality after esophageal and gastric cancer resection.
AB  - BACKGROUND: Contrasting findings on trends and determinants of operative
      mortality after surgery for esophageal and gastric cancer have been reported from
      population-based studies. METHODS: Discharge records of residents in the Veneto
      Region (northeastern Italy) with a diagnosis of esophageal or gastric cancer and
      intervention codes for esophagectomy or gastrectomy were extracted for the years
      2000-2009. In-hospital, 30-day, 90-day, and perioperative (30-day + in-hospital)
      mortality were computed. The influence of patient and hospital variables on in
      hospital mortality was assessed through multilevel models. RESULTS: Overall,
      6,500 resections were performed in the period of 2000-2009, with a 10 % decline
      in the second half of the study period. In-hospital mortality was 4.6 % (5.3 % in
      2000-2004 and 3.8 % in 2005-2009) and was higher for extended total gastrectomy
      and total esophagectomy. In 2005-2009 mortality declined for all resection types
      except extended total gastrectomy (8.0 %). For esophageal procedures, 30-day
      mortality was lower than in-hospital or perioperative mortality. A protective
      effect of procedural volume was found for esophageal but not for gastric
      resections; among gastric procedures, mortality was higher in male patients and
      in extended total gastrectomy patients. CONCLUSIONS: Analyses of discharge
      records allowed investigation at a population level of time trends (downward
      mainly for esophageal resections) and determinants of perioperative mortality
      (hospital volume, gender, and procedure type).

PMID- 22851146
TI  - The implementation of a pilot femur fracture registry at Komfo Anokye Teaching
      Hospital: an analysis of data quality and barriers to collaborative capacity
      building.
AB  - BACKGROUND: Trauma registries are essential for injury surveillance and
      recognition of the burden of musculoskeletal injury in low- and middle-income
      countries (LMICs). The purpose of this study was to pilot a femur fracture
      registry at Komfo Anokye Teaching Hospital (KATH) to assess data quality and
      determine the barriers to research partnering in LMICs. METHODS: All patients
      admitted to KATH with a fracture of the femur, or Arbeitsgemeinschaft fur
      Osteosynthesefragen (AO) class 31, 32, 33, were entered into a locally designed,
      electronic femur fracture database. Patients' characteristics and data quality
      were assessed by using descriptive statistics. Orthopedic trauma research
      barriers and opportunities were identified from key informants at the research
      site and supporting site. RESULTS: Ninety-six femur fracture patients were
      enrolled into the registry over a 5-week period. The majority of patients resided
      in the Ashanti region surrounding the hospital (78 %). Most participants were
      involved in a road traffic crash (58 %) and physiologically stable with a Cape
      Triage Score of yellow upon admission (84 %). AO class 32 femur fractures
      represented the majority of femur fractures (78 %). Median times from injury to
      admission, admission to surgery, and surgery to discharge were 0, 5, and 10 days,
      respectively. Data quality analysis showed that data collected at admission had
      higher rates of completion in the database relative to data collected at various
      follow-up time points. CONCLUSIONS: Data and data quality analyses highlighted
      characteristics of femur fracture patients presenting to KATH as well as the
      technological, administrative support, and hospital systems-based challenges of
      longitudinal data collection in LMICs.

PMID- 22851147
TI  - Survey of surgery and anesthesia infrastructure in Ethiopia.
AB  - BACKGROUND: Information regarding surgical capacity in the developing world is
      limited by the paucity of available data regarding surgical care, infrastructure,
      and human resources in the literature. The purpose of this study was to assess
      surgical and anesthesia infrastructure and human resources in Ethiopia as part of
      a larger study by the Harvard Humanitarian Initiative examining surgical and
      anesthesia capacity in ten low-income countries in Africa. METHODS: A
      comprehensive survey tool developed by the Harvard Humanitarian Initiative was
      used to assess surgical capacity of hospitals in Ethiopia. A total of 20
      hospitals were surveyed through convenience sampling. Eight areas of surgical and
      anesthesia care were examined, including access and availability, access to human
      resources, infrastructure, outcomes, operating room information and procedures,
      equipment, nongovernmental organization delivery of surgical services, and
      pharmaceuticals. Results were obtained over a 1-month period during October 2011.
      RESULTS: There is wide variation in accessibility, with hospital-to-population
      ratios ranging from 1:99,010 to 1:1,082,761. The overall physician to population
      ratio ranges from 1:4715 to 1:107,602. The average hospital has one to two
      operating rooms, 4.2 surgeons, one gynecologist, and 4.5 anesthesia providers
      although in all but three hospitals anesthesiology was provided by nonphysician
      personnel only (i.e., a nurse anesthetist). Access to continuous electricity,
      running water, essential medications, and monitoring systems is very limited in
      all hospitals surveyed, although such access did vary across regions.
      CONCLUSIONS: This survey of Ethiopia's hospital resources attempts to identify
      specific areas of need where resources, education, and development can be
      targeted. Because the major surgical mortality comes from late presentations,
      increasing accessibility through infrastructure development would likely provide
      a major improvement in surgical morbidity and mortality rates. Infrastructure
      limitations of electricity, water, oxygen, and blood banking do not prove to be
      significant barriers to surgical care. The increasing number of physicians is
      promising, although efforts should be directed specifically toward increasing the
      number of anesthesiologists and surgeons in the country.

PMID- 22851148
TI  - Cryopreservation of parathyroid tissue after parathyroid surgery for renal
      hyperparathyroidism: does it really make sense?
AB  - BACKGROUND: Metachronous autotransplantation of cryopreserved parathyroid tissue
      is a technique for treating postoperative hypoparathyroidism after parathyroid
      surgery for renal hyperparathyroidism (rHPT). The aim of the present study was to
      evaluate our institution's experience with metachronous autotransplantation to
      analyze the role of cryopreservation in the treatment of rHPT and to determine
      for whom and when cryopreservation of parathyroid tissue should be deemed
      necessary. METHODS: A prospective database of patients with rHPT who underwent
      surgery between 1976 and 2011 was screened for patients with hypoparathyroidism
      who received a metachronous autotransplantation. Data were analyzed regarding
      clinical data, histopathological findings of the cryopreserved parathyroid
      tissues, and patient outcome after metachronous replantation of parathyroid
      tissue. RESULTS: Fifteen of 883 patients with rHPT underwent a metachronous
      autotransplantation under local anesthesia at a mean time of 23 months following
      the last cervical surgery. Histopathology of the parathyroid tissue chosen for
      transplantation revealed a necrosis rate of 0 % in 14 and 70 % in one patient.
      Mean preoperative serum calcium and parathyroid hormone (PTH) levels were 2.0
      mmol/l and 3.7 pg/ml, respectively. Autotransplantation raised mean serum calcium
      and PTH levels to 2.2 mmol/l and 97.5 pg/ml, respectively, after a mean follow-up
      of 78 months. CONCLUSIONS: Metachronous autotransplantation following parathyroid
      surgery in patients with rHPT effectively normalizes PTH and calcium levels. The
      success rate is high if an adequate cryopreservation procedure is applied.
      However, it is rarely necessary, and therefore the cryopreservation of
      parathyroid tissue in all patients has to be questioned, at least from an
      economic point of view.

PMID- 22851149
TI  - Designing a contextually appropriate surgical training program in low-resource
      settings: the Botswana experience.
AB  - BACKGROUND: The global burden of surgical disease and severe shortage of trained
      surgeons around the world are now widely recognized. The greatest challenge in
      improving access to surgical care lies in sub-Saharan Africa, where the number of
      surgeons per population is lowest. One part of the solution may be to create
      programs to train surgeons locally. We present our experience with an approach to
      designing a contextually appropriate surgical curriculum in Botswana. METHODS:
      Surgical logbooks from the largest tertiary care center in Botswana, dating from
      2004 through 2010, were analyzed to yield total case numbers within clearly
      defined categories. Case numbers and local surgical opinion were combined to
      design a contextually relevant curriculum, with the Surgical Council on Resident
      Education curriculum as a template. RESULTS: Logbook analysis revealed that
      general surgeons in Botswana manage burns and perform a large number of skin
      grafts and extremity amputations. However, they perform few colonoscopies and
      complex laparoscopic procedures. The new curriculum included greater emphasis on
      surgical subspecialty procedures and surgical management of locally relevant
      conditions, such as the complications of infectious diseases. Less emphasis was
      placed on management of uncommon conditions such as inflammatory bowel disease.
      CONCLUSIONS: There are important differences in the scope of general surgery and
      the knowledge and skills required by general surgeons in Botswana compared with
      their North American counterparts. We present a simple and inexpensive approach
      that could serve as a potential model for designing contextually relevant
      surgical training programs in other low-resource settings.

PMID- 22851150
TI  - Disparities in access to surgical care within a lower income country: an alarming
      inequity.
AB  - BACKGROUND: Surgical care is not uniformly available worldwide. Inequities in
      surgical care and access may also vary within countries, and the present study
      aimed to explore these disparities in Pakistan. METHODS: The National Health
      Survey of Pakistan was analyzed. The proportion of people with a history of
      abdominal surgery (AS) was calculated and associated factors were determined by
      weighted multivariate logistic regression. Factors tested were age, gender,
      urban/rural residence, province, literacy, community development index (CDI), and
      economic status (ES). The CDI was developed for each sampling unit from select
      household and individual data. The ES was constructed from ownership of assets.
      RESULTS: A total of 59 million adults were represented. Abdominal surgery had
      been performed in 3.2 % adults (95 % confidence interval [CI] = 2.67, 3.84),
      which corresponded to an annual rate of 85.9 abdominal surgeries per 100,000
      population. Wide disparities were noted, with annual rates of AS varying from
      37.8 to 215.6 per 100,000 population. Urban residents were independently twice as
      likely as rural populations to have had AS (95 % CI = 1.3, 2.8). Higher age (OR =
      2.6; 95 % CI = 1.7, 4.0), female gender (OR = 1.5; 95 % CI = 1.1, 2.1), and
      higher ES (OR = 1.9; 95 % CI = 1.2, 2.9) were also independently associated with
      AS. In rural populations ES was the only factor associated with surgery, whereas
      in urban populations gender and CDI had important roles to play. CONCLUSIONS:
      Access to surgical care is disparate and grossly inadequate in Pakistan. This
      likely contributes to significant preventable morbidity and death. Physical
      access to surgical facilities, especially in rural areas and for those with a low
      CDI, is an important concern and should be prioritized in any forthcoming
      national policies.

PMID- 22851151
TI  - Assessment of pediatric surgery capacity at government hospitals in Sierra Leone.
AB  - BACKGROUND: Traditionally, efforts to reduce child mortality in low- and middle
      income countries (LMICs) have focused on infectious diseases. However, surgical
      care is increasingly seen as an important component of primary health care. To
      understand the baseline surgical capacity in LMICs, a number of studies have
      recently been published, but none has focused on pediatric surgery. METHODS: The
      Surgeons OverSeas (SOS) Personnel, Infrastructure, Procedures, Equipment and
      Supplies (PIPES) survey was used to collect surgical capacity data from
      government hospitals in Sierra Leone. The data were analyzed specifically to
      identify baseline needs for pediatric surgery. RESULTS: Nine hospitals were
      assessed, and all had a functioning laboratory to test blood and urine and were
      capable of undertaking resuscitation, suturing, wound debridement, incision and
      drainage of an abscess, appendectomy, and male circumcision. However, in only 67
      % could a pediatric hernia repair be performed, and in none were more complex
      procedures such as cleft lip and clubfoot repairs performed. Fewer than 50 % of
      facilities had sufficient gloves, nasogastric tubes, intravenous cannulas,
      syringes, needles, sutures, urinary catheters, infusion sets, anesthesia
      machines, or compressed oxygen. CONCLUSIONS: Using the standard PIPES tool, we
      found severe deficiencies in the pediatric surgical capacity at government
      hospitals in Sierra Leone. However, a pediatric-specific tool is required to
      understand more accurately the pediatric surgical situation.

PMID- 22851152
TI  - Possible health impacts of naturally occurring uptake of aristolochic acids by
      maize and cucumber roots: links to the etiology of endemic (Balkan) nephropathy.
AB  - Aristolochic acids (AAs) are nephrotoxic and carcinogenic derivatives found in
      several Aristolochia species. To date, the toxicity of AAs has been inferred only
      from the effects observed in patients suffering from a kidney disease called
      "aristolochic acid nephropathy" (AAN, formerly known as "Chinese herbs
      nephropathy"). More recently, the chronic poisoning with Aristolochia seeds has
      been considered to be the main cause of Balkan endemic nephropathy, another form
      of chronic renal failure resembling AAN. So far, it was assumed that AAs can
      enter the human food chain only through ethnobotanical use (intentional or
      accidental) of herbs containing self-produced AAs. We hypothesized that the roots
      of some crops growing in fields where Aristolochia species grew over several
      seasons may take up certain amounts of AAs from the soil, and thus become a
      secondary source of food poisoning. To verify this possibility, maize plant (Zea
      mays) and cucumber (Cucumis sativus) were used as a model to substantiate the
      possible significance of naturally occurring AAs' root uptake in food chain
      contamination. This study showed that the roots of maize plant and cucumber are
      capable of absorbing AAs from nutrient solution, consequently producing strong
      peaks on ultraviolet HPLC chromatograms of plant extracts. This uptake resulted
      in even higher concentrations of AAs in the roots compared to the nutrient
      solutions. To further validate the measurement of AA content in the root
      material, we also measured their concentrations in nutrient solutions before and
      after the plant treatment. Decreased concentrations of both AAI and AAII were
      found in nutrient solutions after plant growth. During this short-term
      experiment, there were much lower concentrations of AAs in the leaves than in the
      roots. The question is whether these plants are capable of transferring
      significant amounts of AAs from the roots into edible parts of the plant during
      prolonged experiments.

PMID- 22851153
TI  - Use of the location-based social networking application GRINDR as a recruitment
      tool in rectal microbicide development research.
AB  - Mobile phone social networking applications such as GRINDR are potential tools
      for recruitment of men who have sex with men (MSM) for HIV prevention research.
      Demographics and sexual risk behaviors of men recruited through GRINDR and
      through traditional media were compared. GRINDR participants were younger (mean
      age 31 vs. 42, p < 0.0001), more White identified (44 vs. 30 %, p < 0.01), and
      had more sex partners in the previous 14 days (1.88 vs. 1.10, p < 0.05) than
      other recruits. Email responses were less successful for enrollment than phone
      calls (5 vs. 50 %). This approach resulted in successful recruitment of younger
      and more educated, White identified MSM.

PMID- 22851154
TI  - Unexpectedly high injection drug use, HIV and hepatitis C prevalence among female
      sex workers in the Republic of Mauritius.
AB  - Female sex workers (FSW) often have a disproportionately high prevalence of HIV
      infection and they, along with their clients, are considered a core group
      contributing to the transmission of HIV in many countries. In 2010, females who
      reported having vaginal/anal/oral sex in the last 6 months with a male in
      exchange for money or gifts, aged >=15 years, and living in Mauritius were
      recruited into a survey using respondent driven sampling. Consenting females (n =
      299) completed a behavioral questionnaire and provided venous blood for HIV, HCV
      and HBV testing. HIV seroprevalence among FSW was 28.9 % and 43.8 % were infected
      with HCV; among HIV seropositive FSW, 88.2 % were also infected with HCV. Almost
      40 % of FSW reported injecting drugs sometime in their lives and 30.5 % of all
      FSW reported doing so in the previous 3 months. Among those who ever injected
      drugs, 82.5 % did so in the past 3 months and among those 60 % reported injecting
      drugs at least once a day. Among FSW who ever injected drugs, 17.5 % reported
      sharing a needle at last injection. Regression analyses found injection drug use
      behaviors to be positively associated with HIV seroprevalence. These findings
      indicate that FSW, especially those who inject drugs, are at high risk for HIV
      and HCV infection and transmission and illustrates the need for gender responsive
      HIV and injection drug use prevention and treatment models that respond to the
      unique situations that affect this population.

PMID- 22851155
TI  - Sexual risk behavior and type of sexual partners in transnational indigenous
      migrant workers.
AB  - Indigenous migrant workers (IMWs) have a high vulnerability to HIV and STDs due
      to poverty and marginalization. This study examined factors associated with
      sexual risk behavior (SRB) according to type of partner in transnational young
      male IMWs at a sugar cane agro-industrial complex in western Mexico. A total of
      192 sexually active IMWs were recruited from four laborer shelters to participate
      in a sexual partner survey. The IMWs were interviewed about their sexual partners
      and practices over the last 12 months during which it emerged that they had had a
      total of 360 sexual partners. Multiple linear regression analyses were performed
      to identify factors related to SRB in 222 main (spouse, mistress and girlfriend)
      and 138 casual partners (colleague, friend, casual encounter and sex worker).
      Results showed a significantly higher SRB score with casual partners. For the
      main partner regression model, prior exposure to HIV- and STD-preventive
      information and sexual intercourse with higher employment status partners (formal
      workers vs. self-employed in informal activities and unemployed) were associated
      with lower SRB scores, but if the sexual relations occurred in Mexico (vs. the
      U.S.), the SRB scores increased. For the casual partner model, the practice of
      survival sex (sex in exchange for basic needs), sexual relations in Mexico (vs.
      the U.S.), and being a circular migrant (person traveling for temporary work to
      return home when the contract is over) were related to higher SRB scores.
      Findings support the implementation of preventive interventions using different
      messages depending on the type of partners, main or casual, within the labor
      migrant context.

PMID- 22851156
TI  - Natural-agent mechanisms and early-phase clinical development.
AB  - The evolution of chemoprevention research continues in exciting new directions.
      Large chemoprevention trials in unselected patients have often been negative, but
      this trend promises to be reversed by more-focused and novel trial designs
      emphasizing the identification of molecular targets and predictive biomarkers.
      Phase 0 designs, blood and tissue-based biomarkers, and surrogate endpoints are
      examples of important features of new prevention-trial design. Breakthroughs in
      the identification of novel mechanisms of carcinogenesis have contributed to a
      better understanding of key signaling pathways in cancer development. There has
      been substantial progress in elucidating molecular targets of promising synthetic
      and natural agents such as epigallocatechin gallate, indole-3-carbinol, myo
      inositol, and deguelin, raising great optimism that biomarkers predicting
      efficacy, such as those associated with metformin effects, will be identified.
      This review will highlight several promising natural agents and how early
      clinical development may elucidate their role in personalized cancer
      chemoprevention.

PMID- 22851157
TI  - Cancer chemopreventive and therapeutic potential of guggulsterone.
AB  - Guggulsterone (GS) is a phytosterol derived from the gum resin of guggul plants
      that have been used traditionally to treat various disorders such as burns,
      wounds, gastric ulcer, cough, gum diseases, urinary complaints, diarrhea, stomach
      cramps, fascioliasis, and intestinal worms. It has anti-inflammatory and
      antioxidative properties and has recently attracted substantial attention due to
      its cancer chemopreventive and therapeutic potential exemplified by its
      antiproliferative, antimetastatic, and proapoptotic properties in many cancer
      cell lines and animal models. This review highlights some of the cancer
      chemopreventive/therapeutic targets of GS and the underlying molecular
      mechanisms.

PMID- 22851158
TI  - Energetics of ligand binding to G-quadruplexes.
AB  - G-quadruplex ligands are potential anticancer agents as telomerase inhibitors and
      potential transcriptional regulators of oncogenes. The search for best-in-class
      drugs is addressed to identify small molecules able to promote and stabilize G
      quadruplex structures. What features should the G-quadruplex ligands possess?
      They should have selective antiproliferative effects on cancer cells and induce
      telomerase inhibition or oncogene suppression. One of the main challenges in
      their design and synthesis is to make the ligands selective for G-quadruplex DNA.
      These features should be amplified by careful analyses of physico-chemical
      aspects of G-quadruplex-drug interactions. In particular, the study of the
      energetics of G-quadruplex-drug interactions can enhance drug design by providing
      thermodynamic parameters that give quantitative information on the biomolecular
      interactions important for binding. The main methodologies used to gain
      information on energetics of binding are based on spectroscopic or calorimetric
      principles. Spectroscopic techniques such as fluorescence and circular dichroism
      are rapid and cheap methods, but are not sufficient to characterize completely
      the thermodynamics of interaction. Calorimetric techniques such as isothermal
      titration calorimetry offer a direct measure of binding enthalpy, in addition to
      the stoichiometry and affinity constants. With the complete thermodynamic
      signature of drug-target interaction, dissecting the enthalpic and entropic
      components of binding is possible, which can be a useful aid to decision-making
      during drug optimization.

PMID- 22851159
TI  - Endosialidases: Versatile Tools for the Study of Polysialic Acid.
AB  - Polysialic acid is an alpha2,8-linked N-acetylneuraminic acid polymer found on
      the surface of both bacterial and eukaryotic cells. Endosialidases are
      bacteriophage-borne glycosyl hydrolases that specifically cleave polysialic acid.
      The crystal structure of an endosialidase reveals a trimeric mushroom-shaped
      molecule which, in addition to the active site, harbors two additional polysialic
      acid binding sites. Folding of the protein crucially depends on an intramolecular
      C-terminal chaperone domain that is proteolytically released in an intramolecular
      reaction. Based on structural data and previous considerations, an updated
      catalytic mechanism is discussed. Endosialidases degrade polysialic acid in a
      processive mode of action, and a model for its mechanism is suggested. The review
      summarizes the structural and biochemical elucidations of the last decade and the
      importance of endosialidases in biochemical and medical applications. Active
      endosialidases are important tools in studies on the biological roles of
      polysialic acid, such as the pathogenesis of septicemia and meningitis by
      polysialic acid-encapsulated bacteria, or its role as a modulator of the adhesion
      and interactions of neural and other cells. Endosialidase mutants that have lost
      their polysialic acid cleaving activity while retaining their polysialic acid
      binding capability have been fused to green fluorescent protein to provide an
      efficient tool for the specific detection of polysialic acid. 

PMID- 22851160
TI  - Real-time dynamic frequency and shim correction for single-voxel magnetic
      resonance spectroscopy.
AB  - Subject motion during brain magnetic resonance spectroscopy acquisitions
      generally reduces the magnetic field (B0) homogeneity across the volume of
      interest or voxel. This is the case even if prospective motion correction ensures
      that the voxel follows the head. We introduce a novel method for rapidly mapping
      linear variations in B0 across a small volume using two-dimensional excitations.
      The new field mapping technique was integrated into a prospectively motion
      corrected single-voxel 1H magnetic resonance spectroscopy sequence. Interference
      with the magnetic resonance spectroscopy measurement was negligible, and there
      was no penalty in scan time. Frequency shifts were also measured continuously,
      and both frequency and first-order shim corrections were applied in real time.
      Phantom experiments and in vivo studies demonstrated that the resulting motion-
      and shim-corrected sequence is able to mitigate line broadening and maintain
      spectral quality even in the presence of large-amplitude subject motion.

PMID- 22851161
TI  - Teaching and learning in dermatology: from Gutenberg to Zuckerberg via way of Von
      Hebra.
AB  - The World Wide Web (www) and other internet-based technologies offer enormous
      potential for enhancing teaching in dermatology. There is also the possibility
      that if these technologies are adopted uncritically, either because of ignorance
      of how people learn, or because they are viewed primarily as ways to reduce
      institutional costs, that they might diminish learning, thereby reducing the
      value proposition that undergraduate students receive from Medical Schools. I
      review the history of recent technological change with a focus on what value such
      technologies bring to both student and institution. After summarising some of the
      core principles underpinning successful learning, and modern theories of medical
      expertise, I critically discuss some of the ways the Web and allied technologies
      might enhance the learning of dermatology.

PMID- 22851162
TI  - Dynamics of target-mediated drug disposition: characteristic profiles and
      parameter identification.
AB  - In this paper we present a mathematical analysis of the basic model for target
      mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we
      give a qualitative characterisation of ligand versus time graphs for different
      dosing regimes and derive accurate analytic approximations of different phases in
      the temporal behaviour of the system. These approximations are used to estimate
      model parameters, give analytical approximations of such quantities as area under
      the ligand curve and clearance. We formulate conditions under which a suitably
      chosen Michaelis-Menten model provides a good approximation of the full TMDD
      model over a specified time interval.

PMID- 22851163
TI  - Costs of predator-induced phenotypic plasticity: a graphical model for predicting
      the contribution of nonconsumptive and consumptive effects of predators on prey.
AB  - Defensive modifications in prey traits that reduce predation risk can also have
      negative effects on prey fitness. Such nonconsumptive effects (NCEs) of predators
      are common, often quite strong, and can even dominate the net effect of
      predators. We develop an intuitive graphical model to identify and explore the
      conditions promoting strong NCEs. The model illustrates two conditions necessary
      and sufficient for large NCEs: (1) trait change has a large cost, and (2) the
      benefit of reduced predation outweighs the costs, such as reduced growth rate. A
      corollary condition is that potential predation in the absence of trait change
      must be large. In fact, the sum total of the consumptive effects (CEs) and NCEs
      may be any value bounded by the magnitude of the predation rate in the absence of
      the trait change. The model further illustrates how, depending on the effect of
      increased trait change on resulting costs and benefits, any combination of strong
      and weak NCEs and CEs is possible. The model can also be used to examine how
      changes in environmental factors (e.g., refuge safety) or variation among
      predator-prey systems (e.g., different benefits of a prey trait change) affect
      NCEs. Results indicate that simple rules of thumb may not apply; factors that
      increase the cost of trait change or that increase the degree to which an animal
      changes a trait, can actually cause smaller (rather than larger) NCEs. We provide
      examples of how this graphical model can provide important insights for empirical
      studies from two natural systems. Implementation of this approach will improve
      our understanding of how and when NCEs are expected to dominate the total effect
      of predators. Further, application of the models will likely promote a better
      linkage between experimental and theoretical studies of NCEs, and foster
      synthesis across systems.

PMID- 22851164
TI  - Synthesis and properties of thiophene-fused benzocarborane.
AB  - The o-carborane-based pi-conjugated compound, benzocarborano- [2,1-b:3,4
      b']dithiophene was synthesized. Its crystal structure revealed high coplanarity
      for the two thiophene rings of the 2,2'-bithiophene skeleton, which is fixed in
      the cisoid structure by the o-carborane unit. Theoretical calculations indicated
      non-aromaticity for its center C(6)  ring moiety as well as decreased HOMO and
      LUMO levels. The o-carborane moiety provides an electron-withdrawing character to
      the 2,2'-bithiophene unit through an inductive effect.

PMID- 22851165
TI  - Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian
      hamsters with liver fluke infection and administration of N-nitrosodimethylamine.
AB  - Chronic infection with Opisthorchis viverrini for many years has been associated
      with the development of hepatobiliary diseases including cholangiocarcinoma. It
      is well known that inflammation is a key component of the tumor microenvironment,
      and that chronic inflammation plays an important role in tumorigenesis.
      Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters
      in order to observe the cancer-related inflammation. The Syrian hamsters were
      divided into 5 groups: uninfected controls; normal Syrian hamsters infected with
      O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini
      (OVis); normal Syrian hamsters infected with O. viverrini and administered N
      nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O.
      viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers
      were later observed for gross pathology and histopathological changes; COX2 was
      analyzed by immunohistochemical staining. We found a decreased number of
      inflammatory cells surrounding the hepatic bile duct in the OVis group, but not
      in the OV and CCAis groups. However, in the CCAis group (with suppressed
      immunity) early appearance and greater severity of cholangiocarcinoma were
      observed; gross pathological examination revealed many cancer nodularities on the
      liver surface, and histopathological studies showed the presence of cancer cells,
      findings which correlated with the predominant expression of COX2. The present
      study suggests that host immune responses are intended to ameliorate pathology,
      and they are also crucially associated with pathogenesis in O. viverrini
      infection; the unbalancing of host immunity may enhance cancer-related
      inflammation.

PMID- 22851166
TI  - Multimodality image fusion-guided procedures: technique, accuracy, and
      applications.
AB  - Personalized therapies play an increasingly critical role in cancer care: Image
      guidance with multimodality image fusion facilitates the targeting of specific
      tissue for tissue characterization and plays a role in drug discovery and
      optimization of tailored therapies. Positron-emission tomography (PET), magnetic
      resonance imaging (MRI), and contrast-enhanced computed tomography (CT) may offer
      additional information not otherwise available to the operator during minimally
      invasive image-guided procedures, such as biopsy and ablation. With use of
      multimodality image fusion for image-guided interventions, navigation with
      advanced modalities does not require the physical presence of the PET, MRI, or CT
      imaging system. Several commercially available methods of image-fusion and device
      navigation are reviewed along with an explanation of common tracking hardware and
      software. An overview of current clinical applications for multimodality
      navigation is provided.

PMID- 22851167
TI  - Identification of conserved amino acids in the herpes simplex virus type 1 UL8
      protein required for DNA synthesis and UL52 primase interaction in the virus
      replisome.
AB  - We have used oriS-dependent transient replication assays to search for species
      specific interactions within the herpes simplex virus replisome. Hybrid
      replisomes derived from herpes simplex virus type 1 (HSV-1) and equine
      herpesvirus type 1 (EHV-1) failed to support DNA replication in cells. Moreover,
      the replisomes showed a preference for their cognate origin of replication. The
      results demonstrate that the herpesvirus replisome behaves as a molecular machine
      relying on functionally important interactions. We then searched for functional
      interactions in the replisome context by subjecting HSV-1 UL8 protein to
      extensive mutagenesis. 52 mutants were made by replacing single or clustered
      charged amino acids with alanines. Four mutants showed severe replication
      defects. Mutant A23 exhibited a lethal phenotype, and mutants A49, A52 and A53
      had temperature-sensitive phenotypes. Mutants A49 and A53 did not interact with
      UL52 primase as determined by co-immunoprecipitation experiments. Using GFP
      tagged UL8, we demonstrate that all mutants were unable to support formation of
      ICP8-containing nuclear replication foci. Extended mutagenesis suggested that a
      highly conserved motif corresponding to mutant A49 serves an important role for
      establishing a physical contact between UL8 and UL52. The replication-defective
      mutations affected conserved amino acids, and similar phenotypes were observed
      when the corresponding mutations were introduced into EHV-1 UL8.

PMID- 22851168
TI  - Glycosphingolipids are essential for intestinal endocytic function.
AB  - Glycosphingolipids (GSLs) constitute major components of enterocytes and were
      hypothesized to be potentially important for intestinal epithelial polarization.
      The enzyme UDP-glucose ceramide glucosyltransferase (Ugcg) catalyzes the initial
      step of GSL biosynthesis. Newborn and adult mice with enterocyte-specific genetic
      deletion of the gene Ugcg were generated. In newborn mutants lacking GSLs at day
      P0, intestinal epithelia were indistinguishable from those in control littermates
      displaying an intact polarization with regular brush border. However, those mice
      were not consistently able to absorb nutritional lipids from milk. Between
      postnatal days 5 and 7, severe defects in intestinal epithelial differentiation
      occurred accompanied by impaired intestinal uptake of nutrients. Villi of mutant
      mice became stunted, and enterocytes lacked brush border. The defects observed in
      mutant mice caused diarrhea, malabsorption, and early death. In this study, we
      show that GSLs are essential for enterocyte resorptive function but are primarily
      not for polarization; GSLs are required for intracellular vesicular transport in
      resorption-active intestine.

PMID- 22851169
TI  - Nicotinic acid adenine dinucleotide phosphate (NAADP) degradation by alkaline
      phosphatase.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous second
      messenger providing a Ca(2+) trigger in a wide range of cell types. However, its
      metabolism is not well understood. Here, we demonstrate the presence of
      endogenous NAADP in HeLa cells. CD38, a promiscuous enzyme described to be
      involved in NAADP metabolism, was not detectable in HeLa cells. In cell-free
      extracts of HeLa cells, NAADP was degraded to nicotinic acid adenine dinucleotide
      (NAAD). The enzyme was enriched in membranes (10,000 * g pellet) and displayed
      characteristics typical of alkaline phosphatase (AP), e.g. pH optimum at 8-9 and
      sensitivity to the inhibitors L-homoarginine and L-leucine. Importantly, NAADP at
      physiological concentrations (50-100 nM) was degraded to NAAD. Expression of AP
      isoenzymes was analyzed in HeLa cells. Based on the results together with
      inhibitor studies, the placental AP isoform emerged as the best candidate for
      NAADP degradation in HeLa cells. In contrast to HeLa cells, Jurkat T cells or
      HEK293 cells did not express any AP isoenzymes and did not display any NAADP 2'
      phosphatase activity. Finally, the placental AP isoform was expressed
      heterologously in HEK293 cells, resulting in reconstitution of NAADP 2'
      phosphatase activity in cell-free extracts. On the basis of the results, we
      provide evidence for AP as the metabolizing enzyme of NAADP in cells that do not
      express CD38.

PMID- 22851170
TI  - Electrophilic aldehydes generated by sperm metabolism activate mitochondrial
      reactive oxygen species generation and apoptosis by targeting succinate
      dehydrogenase.
AB  - Oxidative stress is a major cause of defective sperm function in cases of male
      infertility. Such stress is known to be associated with high levels of superoxide
      production by the sperm mitochondria; however, the causes of this aberrant
      activity are unknown. Here we show that electrophilic aldehydes such as 4
      hydroxynonenal (4HNE) and acrolein, generated as a result of lipid peroxidation,
      target the mitochondria of human spermatozoa and stimulate mitochondrial
      superoxide generation in a dose- and time-dependent manner. The activation of
      mitochondrial electron leakage by 4HNE is shown to involve the disruption of
      succinate dehydrogenase activity and subsequent activation of an intrinsic
      apoptotic cascade beginning with a loss of mitochondrial membrane potential and
      terminating in oxidative DNA adduct formation, DNA strand breakage, and cell
      death. A tight correlation between spontaneous mitochondrial superoxide
      generation and 4HNE content (R(2) = 0.89) in untreated populations of human
      spermatozoa emphasized the pathophysiological significance of these findings. The
      latter also provide a biochemical explanation for the self-perpetuating nature of
      oxidative stress in the male germ line, with the products of lipid peroxidation
      stimulating free radical generation by the sperm mitochondria in a positive
      feedback loop.

PMID- 22851171
TI  - Structure-based analyses reveal distinct binding sites for Atg2 and
      phosphoinositides in Atg18.
AB  - Autophagy is an intracellular degradation system by which cytoplasmic materials
      are enclosed by an autophagosome and delivered to a lysosome/vacuole. Atg18 plays
      a critical role in autophagosome formation as a complex with Atg2 and
      phosphatidylinositol 3-phosphate (PtdIns(3)P). However, little is known about the
      structure of Atg18 and its recognition mode of Atg2 or PtdIns(3)P. Here, we
      report the crystal structure of Kluyveromyces marxianus Hsv2, an Atg18 paralog,
      at 2.6 A resolution. The structure reveals a seven-bladed beta-propeller without
      circular permutation. Mutational analyses of Atg18 based on the K. marxianus Hsv2
      structure suggested that Atg18 has two phosphoinositide-binding sites at blades 5
      and 6, whereas the Atg2-binding region is located at blade 2. Point mutations in
      the loops of blade 2 specifically abrogated autophagy without affecting another
      Atg18 function, the regulation of vacuolar morphology at the vacuolar membrane.
      This architecture enables Atg18 to form a complex with Atg2 and PtdIns(3)P in
      parallel, thereby functioning in the formation of autophagosomes at autophagic
      membranes.

PMID- 22851172
TI  - Nifetepimine, a dihydropyrimidone, ensures CD4+ T cell survival in a tumor
      microenvironment by maneuvering sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA).
AB  - Multiple mechanisms have been proposed by which tumors induce T cell apoptosis to
      circumvent tumor immune-surveillance. Although sarco/endoplasmic reticulum Ca(2+)
      ATPase (SERCA) have long been known to regulate intracellular Ca(2+) homeostasis,
      few studies have examined the role of SERCA in processes of T lymphocyte survival
      and activation. In this context it remains largely unexplored as to how tumors
      jeopardize SERCA function to disable T cell-mediated anti-tumor immunity. Here,
      we show that human CD4(+) T cells in the presence of tumor conditions manifested
      an up-regulation of SERCA3 expression that resulted in development of endoplasmic
      reticulum stress leading to CD4(+) T cell apoptosis. Prostaglandin E(2) produced
      by the tumor cell plays a critical role in up-regulating SERCA3 by enhancing the
      binding of its transcription factor Sp1. Gene manipulation and pharmacological
      approaches further established that an increase in SERCA expression also resulted
      in subsequent inhibition of PKCalpha and -theta and retention of NFkappaB in the
      cytosol; however, down-modulation of SERCA3 expression by a dihydropyrimidone
      derivative, ethyl-4-(3-nitro)-phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine
      5 carboxylate (nifetepimine), protected the CD4(+) T cells from tumor-induced
      apoptosis. In fact, nifetepimine-mediated restoration of PKC activity resulted in
      nuclear translocation of p65NFkappaB, thereby ensuring its survival. Studies
      further undertaken in a tumor-bearing mice model revalidated the immunoprotective
      role of nifetepimine. Our present study thus strongly suggests that imbalance in
      cellular calcium homeostasis is an important factor leading to CD4(+) T cell
      death during cancer and holds promise that nifetepimine may have the potential to
      be used as an immunorestoring agent in cancer bearers.

PMID- 22851173
TI  - The Escherichia coli subtilase cytotoxin A subunit specifically cleaves cell
      surface GRP78 protein and abolishes COOH-terminal-dependent signaling.
AB  - GRP78, a molecular chaperone with critical endoplasmic reticulum functions, is
      aberrantly expressed on the surface of cancer cells, including prostate and
      melanoma. Here it functions as a pro-proliferative and anti-apoptotic signaling
      receptor via NH(2)-terminal domain ligation. Auto-antibodies to this domain may
      appear in cancer patient serum where they are a poor prognostic indicator.
      Conversely, GRP78 COOH-terminal domain ligation is pro-apoptotic and anti
      proliferative. There is no method to disrupt cell-surface GRP78 without
      compromising the total GRP78 pool, making it difficult to study cell-surface
      GRP78 function. We studied six cell lines representing three cancer types. One
      cell line per group expresses high levels of cell-surface GRP78, and the other
      expresses low levels (human hepatoma: Hep3B and HepG2; human prostate cancer: PC3
      and 1-LN; murine melanoma: B16F0 and B16F1). We investigated the effect of
      Escherichia coli subtilase cytoxin catalytic subunit (SubA) on GRP78. We report
      that SubA specifically cleaves cell-surface GRP78 on HepG2, 1-LN, and B16F1 cells
      without affecting intracellular GRP78. B16F0 cells (GRP78(low)) have lower
      amounts of cleaved cell-surface GRP78. SubA has no effect on Hep3B and PC3 cells.
      The predicted 28-kDa GRP78 COOH-terminal fragment is released into the culture
      medium by SubA treatment, and COOH-terminal domain signal transduction is
      abrogated, whereas pro-proliferative signaling mediated through NH(2)-terminal
      domain ligation is unaffected. These experiments clarify cell-surface GRP78
      topology and demonstrate that the COOH-terminal domain is necessary for pro
      apoptotic signal transduction occurring upon COOH-terminal antibody ligation.
      SubA is a powerful tool to specifically probe the functions of cell-surface
      GRP78.

PMID- 22851174
TI  - Structural basis for morpheein-type allosteric regulation of Escherichia coli
      glucosamine-6-phosphate synthase: equilibrium between inactive hexamer and active
      dimer.
AB  - The amino-terminal cysteine of glucosamine-6-phosphate synthase (GlmS) acts as a
      nucleophile to release and transfer ammonia from glutamine to fructose 6
      phosphate through a channel. The crystal structure of the C1A mutant of
      Escherichia coli GlmS, solved at 2.5 A resolution, is organized as a hexamer,
      where the glutaminase domains adopt an inactive conformation. Although the wild
      type enzyme is active as a dimer, size exclusion chromatography, dynamic and
      quasi-elastic light scattering, native polyacrylamide gel electrophoresis, and
      ultracentrifugation data show that the dimer is in equilibrium with a hexameric
      state, in vitro and in cellulo. The previously determined structures of the wild
      type enzyme, alone or in complex with glucosamine 6-phosphate, are also
      consistent with a hexameric assembly that is catalytically inactive because the
      ammonia channel is not formed. The shift of the equilibrium toward the hexameric
      form in the presence of cyclic glucosamine 6-phosphate, together with the
      decrease of the specific activity with increasing enzyme concentration, strongly
      supports product inhibition through hexamer stabilization. Altogether, our data
      allow us to propose a morpheein model, in which the active dimer can rearrange
      into a transiently stable form, which has the propensity to form an inactive
      hexamer. This would account for a physiologically relevant allosteric regulation
      of E. coli GlmS. Finally, in addition to cyclic glucose 6-phosphate bound at the
      active site, the hexameric organization of E. coli GlmS enables the binding of
      another linear sugar molecule. Targeting this sugar-binding site to stabilize the
      inactive hexameric state is therefore suggested for the development of specific
      antibacterial inhibitors.

PMID- 22851175
TI  - Enzymatic engineering of polysialic acid on cells in vitro and in vivo using a
      purified bacterial polysialyltransferase.
AB  - In vertebrates, polysialic acid (PSA) is typically added to the neural cell
      adhesion molecule (NCAM) in the Golgi by PST or STX polysialyltransferase. PSA
      promotes plasticity, and its enhanced expression by viral delivery of the PST or
      STX gene has been shown to promote cellular processes that are useful for repair
      of the injured adult nervous system. Here we demonstrate a new strategy for PSA
      induction on cells involving addition of a purified polysialyltransferase from
      Neisseria meningitidis (PST(Nm)) to the extracellular environment. In the
      presence of its donor substrate (CMP-Neu5Ac), PST(Nm) synthesized PSA directly on
      surfaces of various cell types in culture, including Chinese hamster ovary cells,
      chicken DF1 fibroblasts, primary rat Schwann cells, and mouse embryonic stem
      cells. Similarly, injection of PST(Nm) and donor in vivo was able to produce PSA
      in different adult brain regions, including the cerebral cortex, striatum, and
      spinal cord. PSA synthesis by PST(Nm) requires the presence of the donor CMP
      Neu5Ac, and the product could be degraded by the PSA-specific endoneuraminidase
      N. Although PST(Nm) was able to add PSA to NCAM, most of its product was attached
      to other cell surface proteins. Nevertheless, the PST(Nm)-induced PSA displayed
      the ability to attenuate cell adhesion, promote neurite outgrowth, and enhance
      cell migration as has been reported for endogenous PSA-NCAM. Polysialylation by
      PST(Nm) occurred in vivo in less than 2.5 h, persisted in tissues, and then
      decreased within a few weeks. Together these characteristics suggest that a
      PST(Nm)-based approach may provide a valuable alternative to PST gene therapy.

PMID- 22851176
TI  - Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3)
      coordinates assembly of a multiprotein epithelial sodium channel (ENaC)
      regulatory complex.
AB  - Hormone regulation of ion transport in the kidney tubules is essential for fluid
      and electrolyte homeostasis in vertebrates. A large body of evidence has
      suggested that transporters and channels exist in multiprotein regulatory
      complexes; however, relatively little is known about the composition of these
      complexes or their assembly. The epithelial sodium channel (ENaC) in particular
      is tightly regulated by the salt-regulatory hormone aldosterone, which acts at
      least in part by increasing expression of the serine-threonine kinase SGK1. Here
      we show that aldosterone induces the formation of a 1.0-1.2-MDa plasma membrane
      complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target
      of SGK1. We further show that this complex contains the PDZ domain-containing
      protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3
      physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions
      among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone
      induced manner. These results strongly suggest that CNK3 is a molecular scaffold,
      which coordinates the assembly of a multiprotein ENaC-regulatory complex and
      hence plays a central role in Na(+) homeostasis.

PMID- 22851177
TI  - Modulation of starch digestion for slow glucose release through "toggling" of
      activities of mucosal alpha-glucosidases.
AB  - Starch digestion involves the breakdown by alpha-amylase to small linear and
      branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the
      mucosal alpha-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase
      (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial
      cells, and each contains a catalytic N- and C-terminal subunit. All four subunits
      have alpha-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit
      has an additional exo-debranching activity on the alpha-1,6-linkage. Inhibition
      of alpha-amylase and/or alpha-glucosidases is a strategy for treatment of type 2
      diabetes. We illustrate here the concept of "toggling": differential inhibition
      of subunits to examine more refined control of glucogenesis of the alpha
      amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery.
      Recombinant MGAM and SI subunits were individually assayed with alpha-amylolyzed
      waxy corn starch, consisting mainly of maltose, maltotriose, and branched alpha
      limit dextrins, as substrate in the presence of four different inhibitors:
      acarbose and three sulfonium ion compounds. The IC(50) values show that the four
      alpha-glucosidase subunits could be differentially inhibited. The results support
      the prospect of controlling starch digestion rates to induce slow glucose release
      through the toggling of activities of the mucosal alpha-glucosidases by selective
      enzyme inhibition. This approach could also be used to probe associated metabolic
      diseases.

PMID- 22851178
TI  - Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors
      and human platelet responsiveness.
AB  - We have used selective inhibitors to determine whether the molecular chaperone
      heat shock protein 90 (HSP90) has an effect on both recombinant and native human
      P2X1 receptors. P2X1 receptor currents in HEK293 cells were reduced by ~70-85% by
      the selective HSP90 inhibitor geldanamycin (2 MUM, 20 min). This was associated
      with a speeding in the time course of desensitization as well as a reduction in
      cell surface expression. Imaging in real time of photoactivatable GFP-tagged P2X
      receptors showed that they are highly mobile. Geldanamycin almost abolished this
      movement for P2X1 receptors but had no effect on P2X2 receptor trafficking.
      P2X1/2 receptor chimeras showed that the intracellular N and C termini were
      involved in geldanamycin sensitivity. Geldanamycin also inhibited native P2X1
      receptor-mediated responses. Platelet P2X1 receptors play an important role in
      hemostasis, contribute to amplification of signaling to a range of stimuli
      including collagen, and are novel targets for antithrombotic therapies. Platelet
      P2X1 receptor-, but not P2Y1 receptor-, mediated increases in intracellular
      calcium were reduced by 40-45% following HSP90 inhibition with geldanamycin or
      radicicol. Collagen stimulation leads to ATP release from platelets, and calcium
      increases to low doses of collagen were also reduced by ~40% by the HSP90
      inhibitors consistent with an effect on P2X1 receptors. These studies suggest
      that HSP90 inhibitors may be as effective as selective antagonists in regulating
      platelet P2X1 receptors, and their potential effects on hemostasis should be
      considered in clinical studies.

PMID- 22851179
TI  - A short polybasic segment between the two conserved domains of the beta2a-subunit
      modulates the rate of inactivation of R-type calcium channel.
AB  - Besides opening and closing, high voltage-activated calcium channels transit to a
      nonconducting inactivated state from which they do not re-open unless the plasma
      membrane is repolarized. Inactivation is critical for temporal regulation of
      intracellular calcium signaling and prevention of a deleterious rise in calcium
      concentration. R-type high voltage-activated channels inactivate fully in a few
      hundred milliseconds when expressed alone. However, when co-expressed with a
      particular beta-subunit isoform, beta(2a), inactivation is partial and develops
      in several seconds. Palmitoylation of a unique di-cysteine motif at the N
      terminus anchors beta(2a) to the plasma membrane. The current view is that
      membrane-anchored beta(2a) immobilizes the channel inactivation machinery and
      confers slow inactivation phenotype. beta-Subunits contain one Src homology 3 and
      one guanylate kinase domain, flanked by variable regions with unknown structures.
      Here, we identified a short polybasic segment at the boundary of the guanylate
      kinase domain that slows down channel inactivation without relocating a
      palmitoylation-deficient beta(2a) to the plasma membrane. Substitution of the
      positively charged residues within this segment by alanine abolishes its slow
      inactivation-conferring phenotype. The linker upstream from the polybasic
      segment, but not the N- and C-terminal variable regions, masks the effect of this
      determinant. These results reveal a novel mechanism for inhibiting voltage
      dependent inactivation of R-type calcium channels by the beta(2a)-subunit that
      might involve electrostatic interactions with an unknown target on the channel's
      inactivation machinery or its modulatory components. They also suggest that
      intralinker interactions occlude the action of the polybasic segment and that its
      functional availability is regulated by the palmitoylated state of the beta(2a)
      subunit.

PMID- 22851180
TI  - Up-regulation of translation eukaryotic initiation factor 4E in nucleophosmin 1
      haploinsufficient cells results in changes in CCAAT enhancer-binding protein
      alpha activity: implications in myelodysplastic syndrome and acute myeloid
      leukemia.
AB  - NPM1 is a ubiquitously expressed nucleolar phosphoprotein, the gene for which
      maps to chromosome 5q35 in close proximity to a commonly deleted region
      associated with (del)5q, a type of myelodysplastic syndrome (MDS). This region is
      also a frequent target of deletions in de novo and therapy-related MDS/acute
      myeloid leukemia. Previous studies have shown that Npm1(+/-) mice develop an MDS
      like disease that transforms to acute myeloid leukemia over time. To better
      understand the mechanism by which NPM1 haploinsufficiency causes an MDS
      phenotype, we generated factor-dependent myeloid cell lines from the bone marrow
      of Npm1(+/+) and Npm1(+/-) mice and demonstrated compromised neutrophil-specific
      gene expression in the MNPM1(+/-) cells. We attribute these observations to
      increased levels of the shorter, dominant negative leukemogenic isoform (p30) of
      CCAAT enhancer-binding protein alpha (C/EBPalpha). We show that this increase is
      caused, in part, by elevated levels of the activated translation initiation
      factor eIF4E, overexpression of which also increases translation of C/EBPalphap30
      in HEK293 cells. In a positive feedback loop, eIF4E expression is further
      elevated both at the mRNA and protein levels by C/EBPalphap30 but not by the full
      length C/EBPalphap42. Re-expression of C/EBPalphap42 or NPM1 but not
      C/EBPalphap30 in MNPM1(+/-) cells partially rescues the myeloid phenotype. Our
      observations suggest that the aberrant feed-forward pathway that keeps eIF4E and
      C/EBPalphap30 elevated in NPM1(+/-) cells contributes to the MDS phenotype
      associated with NPM1 deficiency.

PMID- 22851181
TI  - PylSn and the homologous N-terminal domain of pyrrolysyl-tRNA synthetase bind the
      tRNA that is essential for the genetic encoding of pyrrolysine.
AB  - Pyrrolysine is represented by an amber codon in genes encoding proteins such as
      the methylamine methyltransferases present in some Archaea and Bacteria.
      Pyrrolysyl-tRNA synthetase (PylRS) attaches pyrrolysine to the amber-suppressing
      tRNA(Pyl). Archaeal PylRS, encoded by pylS, has a catalytic C-terminal domain but
      an N-terminal region of unknown function and structure. In Bacteria, homologs of
      the N- and C-terminal regions of archaeal PylRS are respectively encoded by pylSn
      and pylSc. We show here that wild type PylS from Methanosarcina barkeri and PylSn
      from Desulfitobacterium hafniense bind tRNA(Pyl) in EMSA with apparent K(d)
      values of 0.12 and 0.13 MUM, respectively. Truncation of the N-terminal region of
      PylS eliminated detectable tRNA(Pyl) binding as measured by EMSA, but not
      catalytic activity. A chimeric protein with PylSn fused to the N terminus of
      truncated PylS regained EMSA-detectable tRNA(Pyl) binding. PylSn did not bind
      other D. hafniense tRNAs, nor did the competition by the Escherichia coli tRNA
      pool interfere with tRNA(Pyl) binding. Further indicating the specificity of
      PylSn interaction with tRNA(Pyl), substitutions of conserved residues in
      tRNA(Pyl) in the variable loop, D stem, and T stem and loop had significant
      impact in binding, whereas those having base changes in the acceptor stem or
      anticodon stem and loop still retained the ability to complex with PylSn. PylSn
      and the N terminus of PylS comprise the protein superfamily TIGR03129. The
      members of this family are not similar to any known RNA-binding protein, but our
      results suggest their common function involves specific binding of tRNA(Pyl).

PMID- 22851182
TI  - Second generation gamma-secretase modulators exhibit different modulation of
      Notch beta and Abeta production.
AB  - The gamma-secretase complex is an appealing drug target when the therapeutic
      strategy is to alter amyloid-beta peptide (Abeta) aggregation in Alzheimer
      disease. gamma-Secretase is directly involved in Abeta formation and determines
      the pathogenic potential of Abeta by generating the aggregation-prone Abeta42
      peptide. Because gamma-secretase mediates cleavage of many substrates involved in
      cell signaling, such as the Notch receptor, it is crucial to sustain these
      pathways while altering the Abeta secretion. A way of avoiding interference with
      the physiological function of gamma-secretase is to use gamma-secretase
      modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Abeta
      formation from producing the amyloid-prone Abeta42 variant to shorter and less
      amyloidogenic Abeta species. The modes of action of GSMs are not fully
      understood, and even though the pharmacology of GSMs has been thoroughly studied
      regarding Abeta generation, knowledge is lacking about their effects on other
      substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF
      MS analysis, we found that two novel, second generation GSMs modulate both Notch
      beta and Abeta production. Moreover, by correlating S3-specific Val-1744 cleavage
      of Notch intracellular domain (Notch intracellular domain) to total Notch
      intracellular domain levels using immunocytochemistry, we also demonstrated that
      Notch intracellular domain is not modulated by the compounds. Interestingly, two
      well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti
      inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Abeta and
      not Notch beta formation, indicating that second generation GSMs and nonsteroidal
      anti-inflammatory drug-based GSMs have different modes of action regarding Notch
      processing.

PMID- 22851184
TI  - Peritoneal carcinosis in apparently benign cortisol producing adrenal adenoma >=
      5 cm in diameter: the need of regular postoperative surveillance.
AB  - BACKGROUND: Clinical and histopathological distinction between benign and
      malignant adrenocortical tumors can be a challenge.Report on 2 patients with
      cortisol producing apparently benign adrenal adenomas >= 5 cm in diameter with
      local malignant recurrence and peritoneal carcinomatosis after endoscopic
      surgery. RESULTS: Case 1: The 59-year-old male presented with adrenal
      hypercortisolism due to a 5.0 cm large adrenal tumor on the left side. A
      retroperitoneoscopic total adrenalectomy was performed. Histologically, a benign
      adrenal adenoma (Weiss score 1, Ki-67 < 2%) was found. 6 months later, the
      patient developed clinically and biochemically recurrent disease with recurrent
      tumor in the left adrenal region and peritoneal carcinomatosis. The patient died
      5 months after second surgery. Case 2: The 32-year-old female was pregnant in
      27th week when presenting with adrenal hypercortisolism due to a 5.5 cm large
      adrenal tumor on the left side. She was operated on using a laparoscopic approach
      and a total adrenalectomy was carried out. Histological examination revealed a
      benign adrenocortical adenoma (Weiss score 1, Ki-67 < 5%). 4 years later, the
      patient came back with clinically and biochemically recurrent disease. Imaging
      showed a 10 cm large tumor in the left retroperitoneum and a diffuse peritoneal
      carcinomatosis. The patient died 2 months after diagnosis. CONCLUSION: Cortisol
      producing adrenal tumors >= 5 cm in diameter are at risk to be misdiagnosed as
      apparently benign. Regular surveillance should be considered in patients
      presenting with large cortisol producing tumors.

PMID- 22851183
TI  - Identification of UV-protective activators of nuclear factor erythroid-derived 2
      related factor 2 (Nrf2) by combining a chemical library screen with computer
      based virtual screening.
AB  - Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master regulator
      of cellular antioxidant defense systems, and activation of this transcription
      factor is a promising strategy for protection of skin and other organs from
      environmental insults. To identify efficient Nrf2 activators in keratinocytes, we
      combined a chemical library screen with computer-based virtual screening. Among
      14 novel Nrf2 activators, the most potent compound, a nitrophenyl derivative of 2
      chloro-5-nitro-N-phenyl-benzamide, was characterized with regard to its molecular
      mechanism of action. This compound induced the expression of cytoprotective genes
      in keratinocytes isolated from wild-type but not from Nrf2-deficient mice. Most
      importantly, it showed low toxicity and protected primary human keratinocytes
      from UVB-induced cell death. Therefore, it represents a potential lead compound
      for the development of drugs for skin protection under stress conditions. Our
      study demonstrates that chemical library screening combined with advanced
      computational similarity searching is a powerful strategy for identification of
      bioactive compounds, and it points toward an innovative therapeutic approach
      against UVB-induced skin damage.

PMID- 22851185
TI  - Extramedullary multiple myeloma presenting as a pituitary mass lesion.
AB  - INTRODUCTION: A plasmocytoma involving the pituitary gland is an extremely rare
      entity, with approximately 22 cases of solitary myeloma or multiple myeloma
      presenting with sellar mass reported in the literature so far. CASE REPORT: Here,
      we report the case of a 71-year-old female patient affected by an extramedullary
      IgG-lambda multiple myeloma presenting as a pituitary mass lesion. We summarize
      the diagnostic approaches that confirmed the diagnosis of multiple myeloma and
      describe treatment outcome after therapy. DISCUSSION: Intrasellar plasmocytoma
      though rare, should be considered in the differential diagnosis of a pituitary
      mass lesion, since associated with different therapeutic and prognostic
      implications. Physicians should be alert for intrasellar plasma cell tumors in
      case of well preserved anterior pituitary function in combination with cranial
      nerve neuropathies and sellar destruction.

PMID- 22851186
TI  - Glucocorticoid receptor density correlates with health risk factors and insulin
      resistance in Caucasian and African American subjects.
AB  - Activation of the hypothalamic-pituitary-adrenal axis leads to secretion of
      cortisol, which binds to peripheral glucocorticoid receptor and mediates a
      complex series of metabolic and immune effects. Cortisol also binds to receptors
      in the hypothalamus and pituitary, and inhibits further secretion of
      adrenocorticotropic hormone thus preventing an excessive response. Excess
      glucocorticoid effect is seen in Cushings disease, adrenal adenomas/carcinomas
      and in glucocorticoid resistance. Within such pathology there are health
      consequences of excessive glucocorticoid action, including obesity, hypertension,
      and glucose intolerance or diabetes. We hypothesized that increased
      glucocorticoid receptor in peripheral tissue might mediate an excess
      glucocorticoid effect in the absence of increased cortisol secretion. The
      objective of the study was to investigate the relationship between glucocorticoid
      receptor density in leukocytes and health risk indices relevant to obesity and
      diabetes in a sample of Caucasian and African American subjects. Comparison of
      glucocorticoid receptor concentration with subject body mass index, percentage
      body fat, waist circumference, insulin resistance, plasma cortisol levels,
      gender, and lipid profiles were conducted. Increased glucocorticoid receptor
      density significantly correlated with body mass index, percentage body fat, waist
      circumference, and insulin resistance. No significant correlation was observed
      for glucocorticoid receptor density with lipid profiles. Furthermore, no
      significant differences were observed in glucocorticoid receptor density between
      Caucasian and African American subjects or male and female participants. Our
      results show that high risk health conditions, such as obesity and type-2
      diabetes, may be associated with a form of hypothalamic-pituitary-adrenal axis
      dysfunction, characterized by localized leukocyte glucocorticoid receptor over
      expression.

PMID- 22851187
TI  - The effect of vitamin D on expression of TGF beta1 in ovary.
AB  - The transforming growth factor beta (TGF-beta) is thought to have important roles
      in several stages of folliculogenesis. Vitamin D is effective in cell
      proliferation, differentition and on estrogen biosynthesis. The aim of the
      present study was to determine the respective role of 1,25-dihydroxyvitamin D3 on
      expression of TGF-beta1 in developing rat ovaries. 24 (one-mounth-old n = 12 and
      adult n = 12) female Wistar rats were enrolled in this study. All animals were
      divided into 4 groups. Group I and II that consist of one-month-old (n = 6) and
      adult rats (n = 6) respectively served as control groups. Intramuscular vitamin
      D3 ( 0,05 MUgr/kg/every other day) was injected for 8 weeks to group III and IV
      which consist of one-mounth-old and adult rats respectively. After last
      injection, ovaries of animals were removed and processed for immunohistochemistry
      assay. No remarkable differences in staining intensity and localization for TGF
      beta1 were observed in group I and group III. TGF immunostaining was also
      predominantly found in oocytes. In granulosa cells, TGF-beta1 immunoreactivity
      was negative. TGF-beta1 immunostaining were observed both in nuclei and cytoplasm
      of granulosa cells in group II. But in group IV granulosa cells and oocytes were
      negative for TGF-beta1. We found that vitamin D administration resulted in a
      decrease in TGF-beta1 levels in the adult rats, but, TGF-beta1 expression did not
      significantly decrease in the newborn rats. However, in multiple linear
      regression analysis, TGF-beta1 expressions were independently associated with
      vitamin D administration. It is observed that Vitamin D attenuated TGF-beta1
      expression. The results of this study suggest that vitamin D may play role in
      folliculogenesis via TGF-beta1.

PMID- 22851188
TI  - Early and late onset of voluntary exercise have differential effects on the
      metabolic syndrome in an obese mouse model.
AB  - In a mouse model for juvenile obesity, we investigated how the age of onset of
      voluntary exercise affects factors of the metabolic syndrome. One exercise group
      had access to running wheels from 3 weeks (representing childhood) and another
      one from 9 weeks on (early adulthood). Both groups were compared to mice without
      exercise. The investigations were performed under 2 diets (standard maintenance
      and high-fat diet). Average daily running activity was independent of diet and
      exercise. On both diets, mice with exercise from 3 weeks on gained 10 g body
      weight and 5 g fat mass less than mice without exercise. The highest body weight
      difference between mice on HFD without exercise and mice on standard maintenance
      diet with exercise was 24 g. Despite the higher energy expenditure during
      exercise, young mice did not increase their energy intake adjusted for lean mass,
      while mice with exercise from 9 weeks had an increased energy intake of 6 kJ per
      day and therefore could not reduce fat mass on both diets. However, mice with
      exercise from 9 weeks had better glucose tolerance at 20 weeks than mice with
      exercise from childhood on. Independently of the age of exercise onset,
      triglycerides were reduced from 2.4 to 1.7 mmol/l on both diets and insulin
      levels from 1.5 to 0.3 and 4.5 to 1.8 ug/ml on standard maintenance and high-fat
      diet, respectively, which represents a considerable improvement. Physical
      activity seems to have long-lasting effects on body composition and health, but
      they are different depending on when exercise has begun.

PMID- 22851189
TI  - Impact of psychological stress caused by the Great East Japan Earthquake on
      glycemic control in patients with diabetes.
AB  - We examined the relationship between psychological stress and the worsening of
      glycemic control in diabetic patients at the time of the Great East Japan
      Earthquake. HbA1c levels in diabetic patients before and after the disaster were
      evaluated with the General Health Questionnaire (GHQ) and other questions
      including those on changes in diet, exercise, psychological stress and drug
      intake in 320 consecutive diabetic patients who had been followed in a diabetes
      clinic. Logistic regression analysis revealed that the total GHQ scores (odds
      ratio [OR] 1.03 [95% confidence interval 1.01-1.06]; p<0.01) and interruption of
      drug intake (OR 4.48 [1.57-12.7]; p=0.01) were independently associated with
      worsening of glycemic control defined as an increase in the HbA1c level equal to
      or greater than 0.5%. Among the scores on the GHQ, those for somatic symptoms (OR
      1.18 [1.01-1.38]; p=0.03) and sleep disturbances or anxiety (OR 1.26 [1.08-1.46];
      p<0.01) were independently associated with glycemic control. These results
      suggest that psychological stress during a disaster has independent effects on
      worsening of glycemic control.

PMID- 22851190
TI  - Diversity analysis of bacterial community compositions in sediments of urban
      lakes by terminal restriction fragment length polymorphism (T-RFLP).
AB  - Bacteria are crucial components in lake sediments and play important role in
      various environmental processes. Urban lakes in the densely populated cities are
      often small, shallow, highly artificial and hypereutrophic compared to rural and
      natural lakes and have been overlooked for a long time. In the present study,
      bacterial community compositions in surface sediments of three urban lakes (Lake
      Mochou, Lake Qianhu and Lake Zixia) in Nanjing City, China, were investigated
      using the terminal restriction fragment length polymorphism (T-RFLP) of PCR
      amplified 16S rRNA gene and clone libraries. Remarkable differences in the T-RFLP
      patterns were observed in different lakes or different sampling stations of the
      same lake. Canonical correspondence analysis indicated that total nitrogen (TN)
      had significant effects on bacterial community structure in the lake sediments.
      Chloroflexi were the most dominant bacterial group in the clone library from Lake
      Mochou (21.7 % of the total clones) which was partly associated with its higher
      TN and organic matters concentrations. However, Bacteroidetes appeared to be
      dominated colonizers in the sediments of Lake Zixia (20.4 % of the total clones).
      Our study gives a comprehensive insight into the structure of bacterial community
      of urban lake sediments, indicating that the environmental factors played a key
      role in influencing the bacterial community composition in the freshwater
      ecosystems.

PMID- 22851191
TI  - Scenedesmus sp. NJ-1 isolated from Antarctica: a suitable renewable lipid source
      for biodiesel production.
AB  - Microalgal lipids are promising alternative feedstocks for biodiesel production.
      Scenedesmus sp. NJ-1, an oil-rich freshwater microalga isolated from Antarctica,
      was identified to be a suitable candidate to produce biodiesel in this study.
      This strain could grow at temperatures ranging from 4 to 35  degrees C. With
      regular decrease in nitrate concentration in the medium, large quantities of
      triacylglycerols accumulated under batch culture conditions detected by thin
      layer chromatography and BODIPY 505/515 fluorescent staining. Scenedesmus sp. NJ
      1 achieved the average biomass productivity of 0.105 g l-1 d-1 (dry weight) and
      nearly the highest lipid content (35 % of dry cell weight) was reached at day 28
      in the batch culture. Neutral lipids accounted for 78 % of total lipids, and
      C18:1 (n-9), C16:0 were the major fatty acids in total lipids, composing 37 and
      20 % of total fatty acids of Scenedesmus sp. NJ-1 grown for 36 days,
      respectively. These results suggested that Scenedesmus sp. NJ-1 was a good source
      of microalgal oils for biodiesel production.

PMID- 22851192
TI  - Isolation of biosurfactant-producing bacteria from the Rancho La Brea Tar Pits.
AB  - This research was conducted to identify culturable surfactant-producing bacterial
      species that inhabit the 40,000-year-old natural asphalt seep at the Rancho La
      Brea Tar Pits in Los Angeles, CA. Using phenanthrene, monocyclic aromatic
      hydrocarbons, and tryptic soy broth as growth substrates, culturable bacteria
      from the tar pits yielded ten isolates, of which three species of gamma
      proteobacteria produced biosurfactants that accumulated in spent culture medium.
      Partially purified biosurfactants produced by these strains lowered the surface
      tension of water from 70 to 35-55 mN/m and two of the biosurfactants produced
      'dark halos' with the atomized oil assay, a phenomenon previously observed only
      with synthetic surfactants. Key findings include the isolation of culturable
      biosurfactant-producing bacteria that comprise a relatively small fraction of the
      petroleum-degrading community in the asphalt.

PMID- 22851193
TI  - Environmental monitoring of linear alkylbenzene sulfonates and physicochemical
      characteristics of seawater in El-Mex Bay (Alexandria, Egypt).
AB  - In the present work, the influence of different physicochemical characteristics
      on the distribution of anionic detergents, linear alkylbenzene sulfonates (LAS),
      was studied. Surface and bottom water samples were collected from eight different
      sites from a small bay near the main sewage discharge of Alexandria City (El-Max
      Bay). The results showed great variations in the concentrations, as a function of
      the regional and seasonal variations. The study revealed that the pH values lie
      in the normal side, with a range of 8.0-8.5 inside the bay and 7.5-7.7 at El-Umum
      Drain effluent. Wide variations, observed between the surface and the bottom
      water of the bay, salinity, dissolved oxygen, oxidizable organic matter, total
      hardness, and total alkalinity, were scattered in the ranges (3.33-42.73
      practical salinity unit), (0.42-8.27 mg O2/l), (0.12-10.49 mg/l), (1.39-8.99
      mg/l), and (0.23-0.48 mg/l), respectively. The regional variations of LAS
      concentrations in the bay waters showed that the concentration decreased as the
      distance from the source of drainage water (El-Umum Drain). The seasonal average
      variations of LAS cleared out that summer and spring periods had the highest
      concentrations at surface (0.13 +/- 0.04 mg LAS/l) and bottom (0.12 +/- 0.10 mg
      LAS/l) layer, which is attributed to increase in population density and human
      activities. The inverse relationships between total LAS concentration and
      salinity, dissolved oxygen, and calcium ions concentration are r = -0.78, 0.50,
      and 0.67, respectively. This is related to the occurrence of the untreated
      wastewater containing detergents, the biodegradation rate of surfactants, and
      strong precipitation of LAS as Ca.

PMID- 22851194
TI  - Water quality in Minho/Mino River (Portugal/Spain).
AB  - Minho River, also called Mino (in Spain), extends to about 300 km from Spain to
      Portugal. The source of the river lies in Spain and in the last 75 km, the river
      defines the border between Portugal and Spain. Under the scope of a cooperation
      project between North Portugal and Galicia region of Spain, titled: "Valorization
      of the natural resources of the Minho/Mino drainage basin", seven water-sampling
      campaigns were carried out during the last 2 years in Minho River basin. Seven
      sampling sites were selected along the international stretch, and five were
      chosen in the main Portuguese and Spanish tributaries of Minho River. Water
      quality based on the physicochemical and microbial parameters was assessed.
      According to the Portuguese legislation for surface waters, the international
      section of Minho River presents a reasonably good water quality (BOD5 <5 mg/L,
      TNK <2 mg/L, and total phosphorous <1 mg P/L). Valenca and Louro were found to be
      the most polluted sampling sites and Louro the most polluted tributary (maximum
      values observed: TSS = 26 mg/L, BOD5 = 6.6 mg O2/L, COD = 20.8 mg O2/L, total
      nitrogen = 9.9 mg N/L; minimum value observed: OD = 1.3 mg O2/L). A one
      dimensional stream water quality model QUAL2Kw was calibrated using data measured
      in field surveys along the international stretch of Minho River. QUAL2Kw was also
      used to predict the impact of flow conditions, discharges, and tributaries on the
      water quality of international stretch of Minho River, essential to establish
      proposals for management and planning of Minho River Basin.

PMID- 22851195
TI  - Levels of lead, cadmium, copper, iron, and zinc in deciduous teeth of children
      living in Irbid, Jordan by ICP-OES: some factors affecting their concentrations.
AB  - The aim of this study was to measure the concentrations of lead (Pb), cadmium
      (Cd), copper (Cu), iron (Fe), and zinc (Zn) in deciduous teeth from children
      living in Jordan and to investigate the affecting factors. Deciduous teeth
      samples (n = 320, without fillings) were collected from 5- to 12-year-old
      children and analyzed for Pb, Cd, Cu, Fe, and Zn using inductively coupled plasma
      optical emission spectrometry. A questionnaire was used to gather information on
      each child, such as sex, age, tooth type (incisors, canines, and molars), tooth
      position within the mouth (upper or lower jaw), caries status, presence of
      amalgam fillings inside the mouth, type of drinking water (tap water, home
      purified water, and plant purified water), and zone of residence (close to or far
      from heavy traffic roads). The mean concentrations of Pb, Cd, Cu, Fe, and Zn were
      30.26, 0.55, 6.23, 34.72, and 128.21 MUg/g, respectively. Our results indicate
      that there is a clear relation between the concentrations of the metals analyzed
      in this study and tooth type, tooth position within the mouth, caries status,
      presence of amalgam fillings inside the mouth, and type of drinking water. No
      significant differences in the concentrations of the five metals analyzed were
      observed due to sex. Our results also show that no significant difference among
      Pb, Cd, Cu, Fe, and Zn concentrations and age among the ages of 5-6, 7-8, 9-10,
      and 11-12, except for Pb, which decreases at age 11-12.

PMID- 22851196
TI  - Hydroxynitrile lyases with alpha/beta-hydrolase fold: two enzymes with almost
      identical 3D structures but opposite enantioselectivities and different reaction
      mechanisms.
AB  - Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrins to yield
      hydrocyanic acid (HCN) and the respective carbonyl compound and are key enzymes
      in the process of cyanogenesis in plants. In organic syntheses, HNLs are used as
      biocatalysts for the formation of enantiopure cyanohydrins. We determined the
      structure of the recently identified, R-selective HNL from Arabidopsis thaliana
      (AtHNL) at a crystallographic resolution of 2.5 A. The structure exhibits an
      alpha/beta-hydrolase fold, very similar to the homologous, but S-selective, HNL
      from Hevea brasiliensis (HbHNL). The similarities also extend to the active sites
      of these enzymes, with a Ser-His-Asp catalytic triad present in all three cases.
      In order to elucidate the mode of substrate binding and to understand the
      unexpected opposite enantioselectivity of AtHNL, complexes of the enzyme with
      both (R)- and (S)-mandelonitrile were modeled using molecular docking
      simulations. Compared to the complex of HbHNL with (S)-mandelonitrile, the
      calculations produced an approximate mirror image binding mode of the substrate
      with the phenyl rings located at very similar positions, but with the cyano
      groups pointing in opposite directions. A catalytic mechanism for AtHNL is
      proposed, in which His236 from the catalytic triad acts as a general base and the
      emerging negative charge on the cyano group is stabilized by main-chain amide
      groups and an alpha-helix dipole very similar to alpha/beta-hydrolases. This
      mechanistic proposal is additionally supported by mutagenesis studies.

PMID- 22851197
TI  - Identification of sites of sympathetic outflow during concurrent recordings of
      sympathetic nerve activity and fMRI.
AB  - The sympathetic division of the nervous system is critical for maintaining both
      resting arterial pressure and for producing changes in regional perfusion
      required by behavioral state changes. A primary determinant of arterial pressure
      is the level of vasoconstriction within skeletal muscle. It is well established
      that there is a tight relationship between dynamic changes in arterial pressure
      and muscle sympathetic nerve activity (MSNA) through the workings of the
      baroreflex. While the central circuitry underlying the baroreflex has been
      extensively investigated in anesthetized experimental animals, few studies have
      investigated the central circuitry responsible for the baroreflex in awake human
      subjects. Recently we were the first to record concurrently MSNA (using
      microneurography) and brain activity (using functional magnetic resonance
      imaging) in awake humans in a series of experiments designed to determine the
      central circuitry underlying the baroreflex in humans. We confirmed that the
      baroreflex involves activity changes within the nucleus tractus solitarius,
      caudal ventrolateral, and rostral ventrolateral medulla. Because conditions such
      as essential hypertension, obesity, and obstructive sleep apnea are all
      characterized by significant increases in resting MSNA, it is important to
      understand both brainstem and cortical sites involved in regulating resting
      levels of MSNA. Future investigations which define cortical sites involved in
      generating and modulating MSNA are important if we are to understand the
      underlying mechanisms of many conditions characterized by hypertension.

PMID- 22851198
TI  - CD163 favors Mycobacterium leprae survival and persistence by promoting anti
      inflammatory pathways in lepromatous macrophages.
AB  - Lepromatous macrophages possess a regulatory phenotype that contributes to the
      immunosuppression observed in leprosy. CD163, a scavenger receptor that
      recognizes hemoglobin-haptoglobin complexes, is expressed at higher levels in
      lepromatous cells, although its functional role in leprosy is not yet
      established. We herein demonstrate that human lepromatous lesions are
      microenvironments rich in IDO+CD163+. Cells isolated from these lesions were
      CD68+IDO+CD163+ while higher levels of sCD163 in lepromatous sera positively
      correlated with IL-10 levels and IDO activity. Different Myco-bacterium leprae
      (ML) concentrations in healthy monocytes likewise revealed a positive correlation
      between increased concentrations of the mycobacteria and IDO, CD209, and CD163
      expression. The regulatory phenotype in ML-stimulated monocytes was accompanied
      by increased TNF, IL-10, and TGF-beta levels whereas IL-10 blockade reduced ML
      induced CD163 expression. The CD163 blockade reduced ML uptake in human
      monocytes. ML uptake was higher in HEK293 cells transfected with the cDNA for
      CD163 than in untransfected cells. Simultaneously, increased CD163 expression in
      lepromatous cells seemed to be dependent on ML uptake, and contributed to
      augmented iron storage in lepromatous macrophages. Altogether, these results
      suggest that ML-induced CD163 expression modulates the host cell phenotype to
      create a favorable environment for myco-bacterial entry and survival.

PMID- 22851199
TI  - Reducing the object orientation dependence of susceptibility effects in gradient
      echo MRI through quantitative susceptibility mapping.
AB  - This study demonstrates the dependence of non-local susceptibility effects on
      object orientation in gradient echo MRI and the reduction of non-local effects by
      deconvolution using quantitative susceptibility mapping. Imaging experiments were
      performed on a 3T MRI system using a spoiled 3D multi-echo GRE sequence on
      phantoms of known susceptibilities, and on human brains of healthy subjects and
      patients with intracerebral hemorrhages. Magnetic field measurements were
      determined from multiple echo phase data. To determine the quantitative
      susceptibility mapping, these field measurements were deconvolved through a
      dipole inversion kernel under a constraint of consistency with the magnitude
      images. Phantom and human data demonstrated that the hypointense region in GRE
      magnitude image corresponding to a susceptibility source increased in volume with
      TE and varied with the source orientation. The induced magnetic field extended
      beyond the susceptibility source and varied with its orientation. In quantitative
      susceptibility mapping, these blooming artifacts, including their dependence on
      object orientation, were reduced, and the material susceptibilities were
      quantified.

PMID- 22851201
TI  - Neuroimaging of attention-deficit/hyperactivity disorder: current neuroscience
      informed perspectives for clinicians.
AB  - The neuroimaging literature on attention-deficit/hyperactivity disorder (ADHD) is
      growing rapidly. Here, we provide a critical overview of neuroimaging studies
      published recently, highlighting perspectives that may be of relevance for
      clinicians. After a comprehensive search of PubMed, Ovid, Web of Science, and
      EMBASE, we located 41 pertinent papers published between January 2011 and April
      2012, comprising both structural and functional neuroimaging studies. This
      literature is increasingly contributing to the notion that the pathophysiology of
      ADHD reflects abnormal interplay among large-scale brain circuits. Moreover,
      recent studies have begun to reveal the mechanisms of action of pharmacological
      treatment. Finally, imaging studies with a developmental perspective are
      revealing the brain correlates of ADHD over the lifespan, complementing clinical
      observations on the phenotypic continuity and discontinuity of the disorder.
      However, despite the increasing potential to eventually inform clinical practice,
      current imaging studies do not have validated applications in day-to-day clinical
      practice. Although novel analytical techniques are likely to accelerate the pace
      of translational applications, at the present we advise caution regarding
      inappropriate commercial misuse of imaging techniques in ADHD.

PMID- 22851202
TI  - Association between ADAM33 T1 polymorphism and susceptibility to asthma in
      Asians.
AB  - OBJECTIVE: The aim of this study was to determine whether the ADAM33 (a
      disintegrin and metalloproteinase domain 33) T1 (rs2280091), T2 (rs2280090), and
      ST+7 (rs574174) polymorphisms confer susceptibility to asthma. METHODS: A meta
      analysis stratified by ethnicity and age was conducted on associations between
      the ADAM33 T1, T2, and ST+7 polymorphisms and asthma. RESULTS: Eleven studies,
      which included 4,124 patients and 7,094 controls, were available for the meta
      analysis. Meta-analysis revealed an association between asthma and the ADAM33 T1
      GG genotype [odds ratio (OR) = 2.257, 95 % confidence interval (CI) = 1.577
      3.228, p = 8.42 * 10(-7)]. Stratification by ethnicity indicated an association
      between this genotype and asthma in Asians (OR = 2.683, 95 % CI = 1.799-4.001, p
      = 1.31 * 10(-7)), and stratification by age indicated an association between it
      and asthma in adults (OR = 1.895, 95 % CI = 1.005-3.573, p = 0.048). However, no
      association was found between asthma and the ADAM33 T2 and ST+7 polymorphisms.
      CONCLUSIONS: This meta-analysis demonstrates that the ADAM33 T1 polymorphism
      confers susceptibility to asthma in Asians, but no association was found between
      the ADAM33 T2 and ST+7 polymorphisms and asthma susceptibility.

PMID- 22851203
TI  - The effect of clodronate on a mevalonate kinase deficiency cellular model.
AB  - BACKGROUND: A potential anti-inflammatory effect of clodronate--an
      aminobisphosphonate--was described to antagonize the pro-inflammatory effects of
      the block in the mevalonate pathway, the main feature of a rare auto-inflammatory
      disease called mevalonate kinase deficiency (MKD). OBJECTIVE: In this study we
      evaluated the potential anti-inflammatory effect of clodronate in MKD--a still
      orphan drug pediatric disease. METHODS: We studied some biological parameters,
      nitric oxide production using Griess reagents and programmed cell death by flow
      cytometry, as common inflammatory parameters in MKD, in the presence of different
      doses of clodronate (1, 10 and 100 MUM). RESULTS: In our cellular model and in
      monocytes from patients with MKD, clodronate induced an increase in programed
      cell death and nitric oxide production in comparison with non-treated cells.
      CONCLUSION: Our findings suggest that clodronate does not have an anti
      inflammatory effect as previously reported but that it increases the epiphenomena
      of this pediatric disease.

PMID- 22851204
TI  - Activity of the leukotriene pathway in Barrett's metaplasia and oesophageal
      adenocarcinoma.
AB  - OBJECTIVE: Leukotriene (LT) B(4) is a lipid inflammatory mediator implicated in
      tumorigenesis in animal models of Barrett's oesophagitis, but little is known
      about the cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)), which have distinct
      inflammatory and tumorigenic actions in other tissues. We recently showed that
      the terminal enzymes for the synthesis of both LT families are highly expressed
      in human oesophageal adenocarcinoma (OA) tissues. This study therefore examined
      the capacity of Barrett's metaplasia (BM) and OA tissues to synthesise LTs in
      vitro. SUBJECTS AND METHODS: Oesophageal biopsies from patients with BM (n = 14),
      high-grade dysplasia (n = 2), OA (n = 11), and squamous control tissues (n = 11)
      were cultured with calcium ionophore A32187 (2 MUM) for 60 min. LTB(4) and
      cysteinyl-leukotrienes were extracted and measured by specific enzyme
      immunoassays. RESULTS: Levels of LTB(4) and cysteinyl-leukotrienes were 8.6-fold
      (P < 0.01) and 2.4-fold (P < 0.02) higher, respectively, in OA tissues than in
      squamous control tissues, but levels in BM tissues (n = 14) were not altered.
      Production of the two LT families correlated across all tissue types (r = 0.62, p
      < 0.00005). CONCLUSIONS: Increased synthesis of LTB(4) and cysteinyl-leukotrienes
      has not previously been shown in human OA tissue and our results may indicate a
      role of these lipids in Barrett's disease progression.

PMID- 22851205
TI  - A phase I trial of oral administration of panobinostat in combination with
      paclitaxel and carboplatin in patients with solid tumors.
AB  - PURPOSE: To determine the maximum tolerated doses and dose-limiting toxicities of
      oral panobinostat in combination with paclitaxel and carboplatin when
      administered to patients with advanced solid tumors. PATIENTS AND METHODS:
      Patients initially received panobinostat twice weekly. Following amendment #1,
      patients received panobinostat three times weekly. Paclitaxel and carboplatin
      were administered intravenously on day 1 of each 21-day treatment cycle. Dose
      escalation continued until the maximum tolerated dose was determined. A total of
      10 patients were treated at the recommended phase II dose to further assess
      safety. RESULTS: Twenty-one patients were enrolled across four different dose
      levels. The dose-limiting toxicity of the combination regimen was
      myelosuppression (neutropenia and thrombocytopenia), which often warranted
      panobinostat dose omissions or reductions. Nearly two-thirds of the patients
      experienced grade 4 neutropenia or grade 3 or 4 thrombocytopenia. Non-hematologic
      toxicities consisted primarily of diarrhea, fatigue, and vomiting, which were
      mild to moderate in intensity. No QTc prolongation was reported. Three partial
      responses were confirmed in patients with carcinoma of unknown primary (two
      patients) and non-small-cell lung cancer (one patient). Eleven additional
      patients reported stable disease as their best response to treatment.
      CONCLUSIONS: The recommended phase II dose is panobinostat 10 mg orally three
      times weekly in combination with paclitaxel 175 mg/m(2) and carboplatin AUC 5
      administered intravenously on day 1 of every 21-day cycle.

PMID- 22851206
TI  - Saccharomyces cerevisiae as a model system to study the response to anticancer
      agents.
AB  - The development of new strategies for cancer therapeutics is indispensable for
      the improvement of standard protocols and the creation of other possibilities in
      cancer treatment. Yeast models have been employed to study numerous molecular
      aspects directly related to cancer development, as well as to determine the
      genetic contexts associated with anticancer drug sensitivity or resistance. The
      budding yeast Saccharomyces cerevisiae presents conserved cellular processes with
      high homology to humans, and it is a rapid, inexpensive and efficient compound
      screening tool. However, yeast models are still underused in cancer research and
      for screening of antineoplastic agents. Here, the employment of S. cerevisiae as
      a model system to anticancer research is discussed and exemplified. Focusing on
      the important determinants in genomic maintenance and cancer development,
      including DNA repair, cell cycle control and epigenetics, this review proposes
      the use of mutant yeast panels to mimic cancer phenotypes, screen and study tumor
      features and synthetic lethal interactions. Finally, the benefits and limitations
      of the yeast model are highlighted, as well as the strategies to overcome S.
      cerevisiae model limitations.

PMID- 22851207
TI  - Mechanism of the bell-shaped profile of ribonuclease a activity: molecular
      dynamic approach.
AB  - Ribonuclease-A is a small enzyme contains an active site with positive charges
      for its substrate. His(12) and His(119) of its active site play critical role in
      enzyme catalysis. Salts show a bell-shaped profile on enzyme activity with an
      optimum salt concentration of about 0.1 M for optimum activity. The mechanism of
      decreased activity of the enzyme at low salt concentrations is not clear. In this
      work, we made a new effort to study the molecular events causing inactivation of
      RNase-A at low concentrations of NaCl. Our molecular dynamic result confirms that
      decrease in salt concentrations below an optimal level leads to an enzyme
      structure with lower dynamism and flexibility than that needed for optimum
      activity.

PMID- 22851208
TI  - Adjustment of Time Perception in the Range of Seconds and Milliseconds: The
      Nature of Time-Processing Alterations in Children With ADHD.
AB  - OBJECTIVE: The nature of time-processing alterations in ADHD was assessed by
      means of duration judgments and temporal set-shifting tasks lasting several
      seconds and milliseconds. METHOD: After training with visual sample stimuli for
      long and short durations, 31 children with ADHD and 29 controls estimated the
      durations of test stimuli. During testing, the temporal context was
      systematically varied by shifting the duration of stimulus sets to longer or
      shorter intervals. RESULTS: Children with ADHD generally overestimated the
      durations of stimuli on the seconds scale. Their assessment of stimuli on the
      milliseconds scale can be characterized as less-efficient adaptations to new
      temporal sets alongside otherwise normal discrimination performance. CONCLUSION:
      Findings support a pure time perception alteration in ADHD. In addition, results
      provide first evidence that difficulties in mental set-shifting, which have been
      reported for other tasks, extend to temporal processing in children with ADHD.

PMID- 22851209
TI  - Is there a link between motor performance variability and social-communicative
      impairment in children with ADHD-CT: a kinematic study using an upper limb fitts'
      aiming task.
AB  - OBJECTIVE: This study investigated the relationship between motor performance and
      social-communicative impairment in children with ADHD-combined type (ADHD-CT).
      METHOD: An upper limb Fitts' aiming task was used as a measure of motor
      performance and the Social Responsiveness Scale as a measure of social
      communicative/autistic impairment in the following groups: ADHD-CT (n = 11) and
      typically developing (TD) controls (n = 10). RESULTS: Children with ADHD-CT
      displayed greater variability in their movements, reflected in increased error
      variance over repeated aiming trials compared with TD controls. Motor performance
      variability was associated with social-communicative deficits in the ADHD-CT but
      not in the TD group. CONCLUSION: Social-communicative impairments further
      complicate the clinical picture of ADHD-CT; therefore, further research in this
      area is warranted to ascertain whether a particular pattern of motor disturbance
      in children with ADHD-CT may be clinically useful in identifying and assessing
      children with a more complex ADHD presentation.

PMID- 22851210
TI  - Increasing teachers' knowledge about ADHD and learning disorders: an
      investigation on the role of a psychoeducational intervention.
AB  - OBJECTIVE: To investigate elementary school teachers' baseline knowledge about
      ADHD and learning disorders (LD) and the impact of a strategy to increase
      awareness of these disorders. METHOD: A total of 37 teachers were selected from
      four elementary schools in the catchment area of the University Hospital, in
      Porto Alegre, Brazil. To evaluate teachers' knowledge, two self-report
      questionnaires about ADHD and LD were applied before and after an awareness
      program on these disorders. RESULTS: The intervention significantly increased
      teachers' knowledge of both disorders, even after adjustment for confounding
      factors (p < .001). In the repeated measures ANCOVA, only teachers' previous
      knowledge of ADHD/LD (p < .001) was significant in predicting score change in
      knowledge before and after the intervention. CONCLUSION: Results suggest the
      efficacy of a brief psychoeducational intervention program for increasing teacher
      awareness and knowledge about ADHD and LD. Future studies are warranted to
      confirm the efficacy and evaluate the long-term impact of this intervention.

PMID- 22851211
TI  - Routine TP53 testing for breast cancer under age 30: ready for prime time?
AB  - It is well known that early-onset breast cancer may be due to an inherited
      predisposition. When evaluating women diagnosed with breast cancer under age 30,
      two important syndromes are typically considered: Hereditary Breast and Ovarian
      Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing
      for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic
      testing for mutations in the TP53 gene. There is a concern that overly
      restrictive testing of TP53 may fail to recognize families with Li-Fraumeni
      syndrome. We reviewed the genetic test results and family histories of all women
      with early-onset breast cancer who had genetic testing of the TP53 gene at the
      Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a
      mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not
      meet current criteria for Li-Fraumeni syndrome. By reviewing similar data
      published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with
      early-onset breast cancer, and who have a negative family history, may have a
      mutation in the TP53 gene. Given the potential benefits versus harms of this
      testing, we discuss the option of simultaneous testing of all three genes (BRCA1,
      BRCA2, and TP53) for women diagnosed with breast cancer before age 30.

PMID- 22851212
TI  - Sub-cellular localization analysis of MSH6 missense mutations does not reveal an
      overt MSH6 nuclear transport impairment.
AB  - Nearly one-third of the identified MSH6 germline mutations deal with single amino
      acid substitutions. For an effective genetic counselling it is necessary to
      clearly elucidate by functional tools the specific sub-processes underlying the
      mismatch repair (MMR) misfunctioning in MSH6 non-truncating mutants. Since the
      MMR repair pathway occurs in the nucleus, we suppose the impairment of MutSalpha
      nuclear trafficking to be a possible Lynch syndrome susceptibility causative
      mechanism. In the present study the MMR status of the tumour, the main clinical
      features of mutation carriers and population data associated to the MSH6 missense
      variants, were complemented with computational data about tolerability
      predictions and amino acid substitution conservation. The selected panel of ten
      potentially pathogenic MSH6 mutations was analyzed in a homologous expression
      system for possible deleterious effects on nucleo-cytoplasmic shuttling through
      the assessment of the sub-cellular localization of the corresponding mutated
      proteins. Localization analysis results do not reveal an apparent role of MSH6
      missense mutations in nuclear import impairment and provide the first hint to
      exclude the MSH6 nuclear translocation sub-process as a possible causative
      mechanisms of MMR misfunctioning.

PMID- 22851213
TI  - Long-term outcomes following Foscan(r)-PDT of basal cell carcinomas.
AB  - BACKGROUND AND OBJECTIVE: In a previous publication we showed that mTHPC-PDT
      (Foscan(r)-PDT) is an effective treatment of basal cell carcinomas (BCCs) in
      "difficult to treat" locations and presented optimized treatment parameters to
      reduce costs and side effects. Now we present long-term results of the same study
      population. STUDY DESIGN/MATERIALS AND METHODS: Following PDT of a total of 460
      BCCs in 117 subjects, the patients/lesions were followed-up for a mean duration
      of 42 (range: 2-72) months. Two patients dropped out of follow-up; 13 patients
      died of unrelated causes. Recurrences were treated either by repeated PDT or
      other established methods. RESULTS: The sustained clearance rate was 93.7% and
      the overall treatment success rate was 90.7%. Kaplan-Meier analysis revealed an
      estimated recurrence free fraction of patients at 5 years of 95.1%, 92.4%, 85.1%,
      and 74.0% for the four different photosensitizer dose groups (0.06-0.15, 0.05,
      0.04, and 0.03 mg/kg). High-risk lesions (recurrences, thickness >3 mm) recurred
      more often than low-risk ones, and recurrences mostly (>50%) occurred during the
      first year of follow-up. CONCLUSION: Long-term outcomes of high-dose (0.06-0.15
      mg/kg) and reduced-dose (0.05 mg/kg) Foscan(r)-PDT in "difficult to treat" BCCs
      compare favorably with other methods, even in high-risk lesions (recurrent and/or
      thick lesions). A recommended combination of treatment parameters for low-dose
      therapy seems to be: 0.05 mg/kg Foscan(r), 24 hours drug-light interval (DLI),
      fluence >=40 J/cm(2) . Prospective randomized studies are needed to look into low
      dose mTHPC-PDT of BCCs in more detail and to directly compare it with other
      treatments.

PMID- 22851214
TI  - Direct cloning, genetic engineering, and heterologous expression of the
      syringolin biosynthetic gene cluster in E. coli through Red/ET recombineering.
AB  - The reconstruction of a natural product biosynthetic pathway from bacteria in a
      vector and subsequent heterologous expression in a technically amenable microbial
      system represents an efficient alternative to empirical traditional methods for
      functional discovery, yield improvement, and genetic engineering to produce
      "unnatural" derivatives. However, the traditional cloning procedure based on
      genomic library construction and screening are complicated due to the large size
      (>10 kb) of most biosynthetic pathways. Here, we describe the direct cloning of a
      partial syringolin biosynthetic gene cluster (sylCDE, 19 kb) from a digested
      genomic DNA mixture of Pseudomonas syringae into a plasmid in which sylCDE is
      under the control of an inducible promoter by one step linear-plus-linear
      homologous recombination (LLHR) in Escherichia coli. After expression in E. coli
      GB05-MtaA, two new syringolin derivatives were discovered. The complete
      syringolin gene cluster was assembled by addition of sylAB and exchange of a
      synthetic bidirectional promoter against the native promoter to drive sylB and
      sylC expression by using Red/ET recombineering. The varying production
      distribution of syringolin derivatives showed the different efficiencies of
      native and synthetic promoters in E. coli. The successful reconstitution and
      expression of the syringolin biosynthetic pathway shows that Red/ET
      recombineering is an efficient tool to clone and engineer secondary metabolite
      biosynthetic pathways.

PMID- 22851216
TI  - MRI-Conditional Cardiac Implantable Electronic Devices: What's New and What Can
      We Expect in the Future?
AB  - OPINION STATEMENT: The use of magnetic resonance imaging (MRI) as a diagnostic
      technique is rapidly expanding. The number of patients who undergo implantation
      of permanent pacemaker, implantable cardioverter defibrillator (ICD), and/or
      cardiac resynchronization therapy devices is increasing in parallel.
      Cardiovascular implants are subject to potentially harmful effects from MRI, and
      the routine use of this imaging modality for patients with standard
      cardiovascular devices is contraindicated. Several recent publications have
      suggested that MRI can safely be performed in standard cardiovascular device
      recipients with appropriate patient selection, device programming, and strict
      monitoring. In addition, MRI "conditional" device systems are now available that
      are specifically designed to be safe in the MRI environment. Such new
      technologies may simplify and improve overall safety of MRI in the setting of
      pacemaker and ICD systems. Although the availability of MRI conditional devices
      represents a significant breakthrough, their current use is limited to specific
      MRI conditions. MRI conditional cardiac device technology will likely continue to
      evolve with increased efforts to improve simplicity, safety, and generalizability
      under all MRI conditions.

PMID- 22851217
TI  - [On the reliability of brainstem electric response audiometry (BERA)].
AB  - BACKGROUND: Brainstem electric response audiometries (BERA) are in clinical use
      for a number of years. The aim of our study was to evaluate data regarding the
      long-term reliability of BERA-determined frequency specific thresholds in hearing
      disabled children. MATERIAL AND METHODS: In a group of 97 hearing disabled
      children we sought to compare Notched-Noise- (NN) BERA threshold as well as Click
      BERA thresholds taken shortly after birth with behavioral audiometry thresholds
      determined after 3.2 years (mean). RESULTS: We found a significant correlation
      between both BERA methods and the behavioral tests. However, the correlation
      coefficients for NN-BERA were higher than for Click-BERA thresholds. CONCLUSION:
      Our results provide evidence for a high reliability of the NN-BERA for
      characterization of early onset hearing disabilities in children. Our data
      suggest that pathologic findings in the Click-BERA should always be followed by a
      frequency specific analysis with NN-BERA.

PMID- 22851218
TI  - Functional neuroanatomy and sleep-disordered breathing: implications for
      autonomic regulation.
AB  - A major concern with sleep-disordered breathing conditions, which include
      obstructive sleep apnea (OSA), central apnea, and congenital central
      hypoventilation syndrome (CCHS), is the high incidence of accompanying autonomic
      dysfunction and metabolic disorders. Patients with OSA show exaggerated
      sympathetic tone, leading to hypertension, cardiac arrhythmia, profuse sweating,
      impaired cerebral perfusion, and stroke. In addition, OSA appears in 86% of obese
      Type II diabetic patients, suggesting common deleterious processes. Autonomic
      deficiencies also appear in CCHS patients, who are often hypoglycemic. The
      impaired autonomic control may stem from injury to central sympathetic and
      parasympathetic regulatory areas resulting from apnea-related inflammation,
      hypoxia, or perfusion-related consequences in OSA, and genetic mutation
      repercussions in CCHS. Disturbed sleep organization from apnea arousals may also
      disrupt hormonal release. Brain areas affected in both OSA and CCHS include
      cortical and limbic regions that influence hypothalamic-regulated sympathetic
      control and hormone release, essential for glycemic regulation, as well as
      parasympathetic nuclei influencing the pancreas and other viscera, and raphe
      serotonergic sites, important for thermal and vascular regulation. Brain injury
      and altered functional responses appear in OSA and CCHS, assessed with magnetic
      resonance imaging techniques, in areas which show regional gray matter loss,
      alterations of free water within tissue, loss of axonal integrity, and disruption
      of functional responses to autonomic and ventilatory challenges. Evaluation of
      neural injury and distortion in functional signals to autonomic challenges in
      localized brain areas can provide insights into common pathological mechanisms
      for dysregulation of hormonal release and autonomic processes in sleep-disordered
      breathing and metabolic disorders.

PMID- 22851215
TI  - Cerebellar function in developmental dyslexia.
AB  - Developmental dyslexia is a genetically based neurobiological syndrome, which is
      characterized by reading difficulty despite normal or high general intelligence.
      Even remediated dyslexic readers rarely achieve fast, fluent reading. Some
      dyslexics also have impairments in attention, short-term memory, sequencing
      (letters, word sounds, and motor acts), eye movements, poor balance, and general
      clumsiness. The presence of "cerebellar" motor and fluency symptoms led to the
      proposal that cerebellar dysfunction contributes to the etiology of dyslexia.
      Supporting this, functional imaging studies suggest that the cerebellum is part
      of the neural network supporting reading in typically developing readers, and
      reading difficulties have been reported in patients with cerebellar damage.
      Differences in both cerebellar asymmetry and gray matter volume are some of the
      most consistent structural brain findings in dyslexics compared with good
      readers. Furthermore, cerebellar functional activation patterns during reading
      and motor learning can differ in dyslexic readers. Behaviorally, some children
      and adults with dyslexia show poorer performance on cerebellar motor tasks,
      including eye movement control, postural stability, and implicit motor learning.
      However, many dyslexics do not have cerebellar signs, many cerebellar patients do
      not have reading problems, and differences in dyslexic brains are found
      throughout the whole reading network, and not isolated to the cerebellum.
      Therefore, impaired cerebellar function is probably not the primary cause of
      dyslexia, but rather a more fundamental neurodevelopmental abnormality leads to
      differences throughout the reading network.

PMID- 22851220
TI  - A proteoliposome containing apolipoprotein A-I mutant (V156K) enhances rapid
      tumor regression activity of human origin oncolytic adenovirus in tumor-bearing
      zebrafish and mice.
AB  - We recently reported that the efficiency of adenoviral gene delivery and virus
      stability are significantly enhanced when a proteoliposome (PL) containing
      apolipoprotein (apo) A-I is used in an animal model. In the current study, we
      tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing
      wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors
      of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad
      injected zebrafish, group showed the lowest tumor tissue volume and nucleic acids
      in the tumor area, whereas injection of Ad alone did not result in adequate
      removal of tumor activity. Reactive oxygen species (ROS) contents increased two
      fold in tumor-bearing zebrafish; however, the V156K-PL-Ad injected group showed a
      40% decrease in ROS levels compared to that in normal zebrafish. After reducing
      the tumor volume with the V156K-PL-Ad injection, the swimming pattern of the
      zebrafish changed to be more active and energetic. The oncolytic effect of PL-Ad
      containing either V156K or WT was about two-fold more enhanced in mice than that
      of Ad alone 34 days after the injection. Immunohistochemical analysis revealed
      that the PL-Ad-injected groups showed enhanced efficiency of viral delivery with
      elevated Ad-E1A staining and a diminished number of proliferating tumor cells.
      Thus, the antitumor effect of oncolytic Ad was strongly enhanced by a PL
      containing apoA-I and its mutant (V156K) without causing side effects in mice and
      zebrafish models.

PMID- 22851221
TI  - Regional variations of T2* in healthy and pathologic achilles tendon in vivo at 7
      Tesla: preliminary results.
AB  - The aim of this study was to investigate T2* in the Achilles tendon (AT), in
      vivo, using a three-dimensional ultrashort time echo (3D-UTE) sequence, to
      compare field strength differences (3 and 7 T) and to evaluate a regional
      variation of T2* in healthy and pathologic tendon. Ten volunteers with no history
      of pain in the AT and five patients with chronic Achilles tendinopathy were
      recruited. 3D-UTE images were measured with the following echo times, at echo
      time = [0.07, 0.2, 0.33, 0.46, 0.59, 0.74, 1.0, 1.5, 2.0, 4.0, 6.0, and 9.0 ms].
      T2* values in the AT were calculated by fitting the signal decay to biexponential
      function. Comparing volunteers between 3 and 7 T, short component T(2s)* was 0.71
      +/- 0.17 ms and 0.34 +/- 0.09 ms (P < 0.05); bulk long component T(2l)* was 12.85
      +/- 1.87 ms and 10.28 +/- 2.28 ms (P < 0.05). In patients at 7 T, bulk T(2s)* was
      0.53 +/- 0.17 ms (P = 0.045, compared to volunteers), T(2l)* was 11.49 +/- 4.28
      ms (P = 0.99, compared to volunteers). The results of this study suggest that the
      regional variability of AT can be quantified by T2* in in vivo conditions.
      Advanced quantitative imaging of the human AT using a 3D-UTE sequence may provide
      additional information to standard clinical imaging. Finally, as the preliminary
      patient data suggest, T(2s)* may be a promising marker for the diagnosis of
      pathological changes in the AT.

PMID- 22851222
TI  - Synthesis, characterization, and use of Nb(V)/Ce(IV)-mixed oxides in the direct
      carboxylation of ethanol by using pervaporation membranes for water removal.
AB  - New catalytic systems based on ceria have been used in the direct carboxylation
      of ethanol. The catalytic behavior of Al(2)O(3) and Nb(2)O(5) loaded ceria is
      compared, the latter showing a better performance. A morphological and structural
      study has been carried out on Nb(2)O(5)/CeO(2) catalysts in order to explain
      their behavior in catalysis. Pervaporation membranes have been used for water
      separation. The synthesis of diethylcarbonate (DEC) has been carried out either
      in a liquid phase (ethanol) pressurized with CO(2) or in supercritical
      conditions. A set-up has been developed that allows the production of quite pure
      DEC (>90%) with recycling of CO(2) and ethanol.

PMID- 22851223
TI  - Fate of selected pharmaceuticals in river waters.
AB  - The aqueous environmental fate of two antibiotics, lincomycin and clarithromycin,
      and an antiepileptic drug, carbamazepine, was investigated by monitoring drugs
      decomposition and identifying intermediates in Po river water (North Italy).
      Initially, control experiments in the dark and under illumination were performed
      on river water spiked with drugs to simulate all possible transformation
      processes occurring in the aquatic system. Under illumination, these
      pharmaceuticals were degraded and transformed into numerous organic intermediate
      compounds. Several species were formed and characterised by analysing MS and
      MS(n) spectra and by comparison with parent molecule fragmentation pathways.
      River water was sampled at three sampling points in an urban area. The selected
      pharmaceuticals were detected in all samples. Eight transformation products
      identified in the laboratory simulation were found in natural river water from
      carbamazepine degradation, three from clarithromycin and two from lincomycin.
      Their transformation occurring in aquatic system mainly involved mono- and poly
      hydroxylation followed by oxidation of the hydroxyl groups.

PMID- 22851224
TI  - Electro-Fenton decolourisation of dyes in an airlift continuous reactor using
      iron alginate beads.
AB  - In this study, electro-Fenton dye degradation was performed in an airlift
      continuous reactor configuration by harnessing the catalytic activity of Fe
      alginate gel beads. Electro-Fenton experiments were carried out in an airlift
      reactor with a working volume of 1.5 L, air flow of 1.5 L/min and 115 g of Fe
      alginate gel beads. An electric field was applied by two graphite bars connected
      to a direct current power supply with a constant potential drop. In this study,
      Lissamine Green B and Reactive Black 5 were selected as model dyes. Fe alginate
      gel beads can be used as an effective heterogeneous catalyst for the degradation
      of organic dyes in the electro-Fenton process, as they are more efficient than
      the conventional electrochemical techniques. At optimal working conditions (3 V
      and pH 2), the continuous process was performed. For both dyes, the degree of
      decolourisation increases when the residence time augments. Taking into account
      hydrodynamic and kinetic behaviour, a model to describe the reactor profile was
      obtained, and the standard deviation between experimental and theoretical data
      was lower than 6%. The results indicate the suitability of the electro-Fenton
      technique to oxidise polluted effluents in the presence of Fe alginate gel beads.
      Moreover, the operation is possible in a continuous airlift reactor, due to the
      entrapment of iron in the alginate matrix.

PMID- 22851225
TI  - Predicting adsorptive removal of chlorophenol from aqueous solution using
      artificial intelligence based modeling approaches.
AB  - The research aims to develop artificial intelligence (AI)-based model to predict
      the adsorptive removal of 2-chlorophenol (CP) in aqueous solution by coconut
      shell carbon (CSC) using four operational variables (pH of solution, adsorbate
      concentration, temperature, and contact time), and to investigate their effects
      on the adsorption process. Accordingly, based on a factorial design, 640 batch
      experiments were conducted. Nonlinearities in experimental data were checked
      using Brock-Dechert-Scheimkman (BDS) statistics. Five nonlinear models were
      constructed to predict the adsorptive removal of CP in aqueous solution by CSC
      using four variables as input. Performances of the constructed models were
      evaluated and compared using statistical criteria. BDS statistics revealed strong
      nonlinearity in experimental data. Performance of all the models constructed here
      was satisfactory. Radial basis function network (RBFN) and multilayer perceptron
      network (MLPN) models performed better than generalized regression neural
      network, support vector machines, and gene expression programming models.
      Sensitivity analysis revealed that the contact time had highest effect on
      adsorption followed by the solution pH, temperature, and CP concentration. The
      study concluded that all the models constructed here were capable of capturing
      the nonlinearity in data. A better generalization and predictive performance of
      RBFN and MLPN models suggested that these can be used to predict the adsorption
      of CP in aqueous solution using CSC.

PMID- 22851228
TI  - Spinal needle navigation by tracked ultrasound snapshots.
AB  - PURPOSE: Ultrasound (US) guidance in facet joint injections has been reported
      previously as an alternative to imaging modalities with ionizing radiation.
      However, this technique has not been adopted in the clinical routine, due to
      difficulties in the visualization of the target joint in US and simultaneous
      manipulation of the needle. METHODS: We propose a technique to increase targeting
      accuracy and efficiency in facet joint injections. This is achieved by
      electromagnetically tracking the positions of the US transducer and the needle,
      and recording tracked US snapshots (TUSS). The needle is navigated using the
      acquired US snapshots. RESULTS: In cadaveric lamb model, the success rate of
      facet joint injections by five orthopedic surgery residents significantly
      increased from 44.4% with freehand US guidance to 93.3% with TUSS guidance.
      Needle insertion time significantly decreased from 47.9 +/- 34.2 s to 36.1 +/-
      28.7 s (mean +/- SD). In a synthetic human spine model, a success rate of 96.7%
      was achieved with TUSS. The targeting accuracy of the presented system in a gel
      phantom was 1.03 +/- 0.48 mm (mean +/- SD). CONCLUSION: Needle guidance with TUSS
      improves the success rate and time efficiency in spinal facet joint injections.
      This technique readily translates also to other spinal needle placement
      applications.

PMID- 22851227
TI  - Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation,
      migration, and differentiation.
AB  - Interleukin-22 (IL-22) is one of the key mediators of keratinocyte alterations in
      psoriasis. IL-22 inhibits keratinocyte differentiation and induces the migration
      of human keratinocytes. Grb2-associated binder 1 (Gab1) has been shown to mediate
      epidermal growth factor-induced epidermal growth and differentiation via
      interaction with the Src homology-2-containing protein-tyrosine phosphatase
      (Shp2). In this investigation, we explore the role of Gab1 and Gab2 in IL-22
      mediated keratinocyte activities. We show that both Gab1 and Gab2 were tyrosine
      phosphorylated in IL-22-stimulated HaCaT cells and human primary epidermal
      keratinocytes and contributed to the activation of Extracellular signal regulated
      kinase 1/2 (Erk1/2) through interaction with Shp2. We further demonstrate that
      HaCaT cells infected with adenoviruses expressing Shp2-binding-defective Gab1/2
      mutants exhibited decreased cell proliferation and migration, as well as
      increased differentiation. Moreover, similar results were observed in HaCaT cells
      infected with adenovirus-based small interfering RNAs targeting Gab1 and/or Gab2.
      Altogether, these data underscore the critical roles of Gab1 and Gab2 in IL-22
      mediated HaCaT cell proliferation, migration, and differentiation.

PMID- 22851230
TI  - Reducing false intracranial pressure alarms using morphological waveform
      features.
AB  - False alarms produced by patient monitoring systems in intensive care units are a
      major issue that causes alarm fatigue, waste of human resources, and increased
      patient risks. While alarms are typically triggered by manually adjusted
      thresholds, the trend and patterns observed prior to threshold crossing are
      generally not used by current systems. This study introduces and evaluates, a
      smart alarm detection system for intracranial pressure signal (ICP) that is based
      on advanced pattern recognition methods. Models are trained in a supervised
      fashion from a comprehensive dataset of 4791 manually labeled alarm episodes
      extracted from 108 neurosurgical patients. The comparative analysis provided
      between spectral regression, kernel spectral regression, and support vector
      machines indicates the significant improvement of the proposed framework in
      detecting false ICP alarms in comparison to a threshold-based technique that is
      conventionally used. Another contribution of this work is to exploit an adaptive
      discretization to reduce the dimensionality of the input features. The resulting
      features lead to a decrease of 30% of false ICP alarms without compromising
      sensitivity.

PMID- 22851229
TI  - Prediction of imagined single-joint movements in a person with high-level
      tetraplegia.
AB  - Cortical neuroprostheses for movement restoration require developing models for
      relating neural activity to desired movement. Previous studies have focused on
      correlating single-unit activities (SUA) in primary motor cortex to volitional
      arm movements in able-bodied primates. The extent of the cortical information
      relevant to arm movements remaining in severely paralyzed individuals is largely
      unknown. We record intracortical signals using a microelectrode array chronically
      implanted in the precentral gyrus of a person with tetraplegia, and estimate
      positions of imagined single-joint arm movements. Using visually guided motor
      imagery, the participant imagined performing eight distinct single-joint arm
      movements, while SUA, multispike trains (MSP), multiunit activity, and local
      field potential time (LFPrms), and frequency signals (LFPstft) were recorded.
      Using linear system identification, imagined joint trajectories were estimated
      with 20-60% variance explained, with wrist flexion/extension predicted the best
      and pronation/supination the poorest. Statistically, decoding of MSP and LFPstft
      yielded estimates that equaled those of SUA. Including multiple signal types in a
      decoder increased prediction accuracy in all cases. We conclude that signals
      recorded from a single restricted region of the precentral gyrus in this person
      with tetraplegia contained useful information regarding the intended movements of
      upper extremity joints.

PMID- 22851231
TI  - Microwave-induced thermoacoustic imaging model for potential breast cancer
      detection.
AB  - In this study, we develop a complete microwave-induced thermoacoustic imaging
      (TAI) model for potential breast cancer imaging application. Acoustic pressures
      generated by different breast tissue targets are investigated by finite
      difference time-domain simulations of the entire TAI process including the
      feeding antenna, matching mechanism, fluidic environment, 3-D breast model, and
      acoustic transducer. Simulation results achieve quantitative relationships
      between the input microwave peak power and the resulting specific absorption rate
      as well as the output acoustic pressure. Microwave frequency dependence of the
      acoustic signals due to different breast tissues is established across a
      broadband frequency range (2.3-12 GHz), suggesting key advantages of
      spectroscopic TAI compare to TAI at a single frequency. Reconstructed
      thermoacoustic images are consistent with the modeling results. This model will
      contribute to design, optimization, and safety evaluation of microwave-induced
      TAI and spectroscopy.

PMID- 22851232
TI  - On-chip systolic networks for real-time tracking of pairwise correlations between
      neurons in a large-scale network.
AB  - The correlation map of neurons emerges as an important mathematical framework for
      a spectrum of applications including neural circuit modeling, neurologic disease
      bio-marking and neuroimaging. However, constructing a correlation map is
      computationally expensive, especially when the number of neurons is large. This
      paper proposes a hardware design using hierarchical systolic arrays to calculate
      pairwise correlations between neurons. Through mapping a computationally
      efficient algorithm for cross-correlation onto a massively parallel structure,
      the hardware is able to construct the correlation maps in a much shorter time.
      The proposed architecture was evaluated using a field programmable gate array.
      The results show that the computational delay of the hardware for constructing
      correlation maps increases linearly with the number of neurons, whereas the
      growth of delay is quadratic for a software-based serial approach. Also, the
      efficiency of our method for detecting abnormal behaviors of neural circuits is
      demonstrated by analyzing correlation maps of retinal neurons.

PMID- 22851233
TI  - A manually operated, advance off-stylet insertion tool for minimally invasive
      cochlear implantation surgery.
AB  - The current technique for cochlear implantation (CI) surgery requires a
      mastoidectomy to gain access to the cochlea for electrode array insertion. It has
      been shown that microstereotactic frames can enable an image-guided, minimally
      invasive approach to CI surgery called percutaneous cochlear implantation (PCI)
      that uses a single drill hole for electrode array insertion, avoiding a more
      invasive mastoidectomy. Current clinical methods for electrode array insertion
      are not compatible with PCI surgery because they require a mastoidectomy to
      access the cochlea; thus, we have developed a manually operated electrode array
      insertion tool that can be deployed through a PCI drill hole. The tool can be
      adjusted using a preoperative CT scan for accurate execution of the advance off
      stylet (AOS) insertion technique and requires less skill to operate than is
      currently required to implant electrode arrays. We performed three cadaver
      insertion experiments using the AOS technique and determined that all insertions
      were successful using CT and microdissection.

PMID- 22851226
TI  - Leptin signaling and circuits in puberty and fertility.
AB  - Leptin is an adipocyte-derived hormone involved in a myriad of physiological
      process, including the control of energy balance and several neuroendocrine axes.
      Leptin-deficient mice and humans are obese, diabetic, and display a series of
      neuroendocrine and autonomic abnormalities. These individuals are infertile due
      to a lack of appropriate pubertal development and inadequate synthesis and
      secretion of gonadotropins and gonadal steroids. Leptin receptors are expressed
      in many organs and tissues, including those related to the control of
      reproductive physiology (e.g., the hypothalamus, pituitary gland, and gonads). In
      the last decade, it has become clear that leptin receptors located in the brain
      are major players in most leptin actions, including reproduction. Moreover, the
      recent development of molecular techniques for brain mapping and the use of
      genetically modified mouse models have generated crucial new findings for
      understanding leptin physiology and the metabolic influences on reproductive
      health. In the present review, we will highlight the new advances in the field,
      discuss the apparent contradictions, and underline the relevance of this complex
      physiological system to human health. We will focus our review on the
      hypothalamic circuitry and potential signaling pathways relevant to leptin's
      effects in reproductive control, which have been identified with the use of
      cutting-edge technologies of molecular mapping and conditional knockouts.

PMID- 22851234
TI  - Quantifying cognitive state from EEG using dependence measures.
AB  - The exquisite human ability to perceive facial features has been explained by the
      activity of neurons particularly responsive to faces, found in the fusiform gyrus
      and the anterior part of the superior temporal sulcus. This study hypothesizes
      and demonstrates that it is possible to automatically discriminate face
      processing from processing of a simple control stimulus based on processed EEGs
      in an online fashion with high temporal resolution using measures of statistical
      dependence applied on steady-state visual evoked potentials. Correlation, mutual
      information, and a novel measure of association, referred to as generalized
      measure of association (GMA), were applied on filtered current source density
      data. Dependences between channel locations were assessed for two separate
      conditions elicited by distinct pictures (a face and a Gabor grating) flickering
      at a rate of 17.5 Hz. Filter settings were chosen to minimize the distortion
      produced by bandpassing parameters on dependence estimation. Statistical analysis
      was performed for automated stimulus classification using the Kolmogorov-Smirnov
      test. Results show active regions in the occipito-parietal part of the brain for
      both conditions with a greater dependence between occipital and inferotemporal
      sites for the face stimulus. GMA achieved a higher performance in discriminating
      the two conditions. Because no additional face-like stimuli were examined, this
      study established a basic difference between one particular face and one nonface
      stimulus. Future work may use additional stimuli and experimental manipulations
      to determine the specificity of the current connectivity results.

PMID- 22851235
TI  - Down-regulation of tumor suppressor in lung cancer 1 (TSLC1) expression
      correlates with poor prognosis in patients with colon cancer.
AB  - Tumor suppressor in lung cancer 1 (TSLC1), a novel tumor suppressor gene, has
      been reported to be frequently inactivated in a variety of human malignant
      tumors. The aim of this study was to detect TSLC1 expression in human colon
      cancer and to analyze its association with prognosis of patients with colon
      cancer. Using quantitative real-time PCR and Western blot analysis, we found
      significantly decreased expression of TSLC1 in primary colon tumor tissues (n =
      30) compared with adjacent normal tissues. Immunohistochemistry analysis also
      found decreased TSLC1 expression in 41.3 % (33/80) colon tumor tissues. In
      clinicopathological analysis, loss of TSLC1 expression significantly correlated
      with female gender and lymph node metastasis of colon cancer patients (P < 0.05).
      In addition, decreased expression of TSLC1 in tumors was found to be closely
      associated with a poor prognosis (P = 0.037, log-rank test), and multivariate
      analysis showed that lower TSLC1 protein expression was an independent prognostic
      factor for colon cancer patients. Our study suggests that down-regulated
      expression of TSLC1 may play an important role in the progression of colon cancer
      and TSLC1 expression may serve as a useful marker for the prognostic evaluation
      of patients with colon cancer.

PMID- 22851236
TI  - Winter protein management during late gestation alters range cow and steer
      progeny performance.
AB  - A 4-yr study was conducted at Corona Range and Livestock Research Center, Corona,
      NM, to establish if a protein-dense self-fed supplement could substitute for a
      traditional hand-fed (range cube) supplement that is less protein dense and
      minimize or maintain cow BW and BCS during late gestation and the subsequent
      steer progeny feedlot performance, health, and economic viability. Late gestation
      cows received one of 3 supplementation strategies: 1) 36% CP cottonseed meal base
      supplement (CSM; positive control) fed 3 times per week, 2) self-fed supplement
      (SMP) comprising 50% animal protein sources (blood meal and feather meal) and 50%
      trace mineral package, or 3) brief and intermittent supplementation of CSM based
      on periods of acute environmental stress (VAR; negative control) by ranch
      management. Initiation of supplementation varied across years due to changing
      forage conditions and climatically imposed grazing constraints but always ended
      approximately 2 wks before calving each year. Across all 4 yr, supplement
      consumption averaged 0.65, 0.21, and 0.04 kg.head(-1).d(-1) for CSM, SMP, and
      VAR, respectively. After weaning, steers were preconditioned for 45 d and were
      received and treated as custom fed commercial cattle at a feedlot in mid November
      each year. Cow BW and BCS were not influenced (P >= 0.13) by prepartum
      supplementation; however, the strategy did have an effect on BW and BCS change
      with cows managed in the VAR group. Cows managed in the VAR group lost the
      greatest (P < 0.05) amount of BW and BCS whereas no differences were measured
      between CSM and SMP groups. Prepartum supplementation strategies did not
      influence (P = 0.98) pregnancy rates. Calf weaning, initial feedlot and final BW,
      and HCW were unaffected (P >= 0.80) by prepartum supplementation of the dam.
      Steers from dams fed CSM and VAR had a greater percentage treated for sickness
      than SMP steers (P = 0.03), which resulted in a tendency (P = 0.07) for medicine
      costs to be greater in steers from CSM and VAR cows. The use of a self-fed
      package supplement was equally effective as use of a traditional hand-fed,
      oilseed-based supplement in maintaining BW and BCS during late gestation. In
      addition, these results imply that although nutrition treatment of cows during
      the prenatal period had no effect on calf growth performance, calves from cows
      fed SMP had improved feedlot health.

PMID- 22851237
TI  - Effects of twenty-four hour transport or twenty-four hour feed and water
      deprivation on physiologic and performance responses of feeder cattle.
AB  - The objective of this study was to compare the effects of 24-h road transport or
      24-h feed and water deprivation on acute-phase and performance responses of
      feeder cattle. Angus * Hereford steers (n = 30) and heifers (n = 15) were ranked
      by gender and BW (217 +/- 3 kg initial BW; 185 +/- 2 d initial age) and randomly
      assigned to 15 pens on d -12 of the experiment (3 animals/pen; 2 steers and 1
      heifer). Cattle were fed alfalfa-grass hay ad libitum and 2.3 kg/animal daily (DM
      basis) of a corn-based concentrate throughout the experiment (d -12 to 28). On d
      0, pens were randomly assigned to 1 of 3 treatments: 1) transport for 24 h in a
      livestock trailer for 1,200 km (TRANS), 2) no transport but feed and water
      deprivation for 24 h (REST), or 3) no transport and full access to feed and water
      (CON). Treatments were concurrently applied from d 0 to d 1. Total DMI was
      evaluated daily from d -12 to d 28. Full BW was recorded before treatment
      application (d -1 and 0) and at the end of experiment (d 28 and 29). Blood
      samples were collected on d 0, 1, 4, 7, 10, 14, 21, and 28. Mean ADG was greater
      (P < 0.01) in CON vs. TRANS and REST cattle but similar (P = 0.46) between TRANS
      and REST cattle (1.27, 0.91, and 0.97 kg/d, respectively; SEM = 0.05). No
      treatment effects were detected for DMI (P >= 0.25), but CON had greater G:F vs.
      TRANS (P < 0.01) and REST cattle (P = 0.08) whereas G:F was similar (P = 0.21)
      between TRANS and REST cattle. Plasma cortisol concentrations were greater (P <=
      0.05) in REST vs. CON and TRANS cattle on d 1, 7, 14, and 28 and also greater (P
      = 0.02) in TRANS vs. CON cattle on d 1. Serum NEFA concentrations were greater (P
      < 0.01) in REST and TRANS vs. CON cattle on d 1 and greater (P < 0.01) in REST
      vs. TRANS cattle on d 1. Plasma ceruloplasmin concentrations were greater (P =
      0.04) in TRANS vs. CON cattle on d 1, greater (P = 0.05) in REST vs. CON on d 4,
      and greater (P <= 0.05) in REST vs. TRANS and CON on d 14. Plasma haptoglobin
      concentrations were greater (P < 0.01) in TRANS vs. CON and REST cattle on d 1
      and greater (P <= 0.05) for REST vs. TRANS and CON cattle on d 7. In conclusion,
      24-h transport and 24-h nutrient deprivation elicited acute-phase protein
      reactions and similarly reduced feedlot receiving performance of feeder cattle.
      These results suggest that feed and water deprivation are major contributors to
      the acute-phase response and reduced feedlot receiving performance detected in
      feeder cattle transported for long distances.

PMID- 22851238
TI  - Relationship of whole body nitrogen utilization to urea kinetics in growing
      steers.
AB  - Urea kinetics were measured in 2 experiments, with treatments designed to change
      protein deposition by the animal. Our hypothesis was that increased protein
      deposition by cattle (Bos taurus) would reduce urea production and recycling to
      the gastrointestinal tract. Urea kinetics were measured by continuous intravenous
      infusion of (15)N(15)N-urea followed by measurement of enrichment in urinary urea
      at plateau. In Exp. 1, 6 steers (139 kg) were maintained in a model in which
      leucine was the most limiting AA. Treatments were arranged as a 2 * 3 factorial
      and were provided to steers in a 6 * 6 Latin square design. Leucine treatments
      included 0 or 4 g/d of abomasally supplemented L-leucine, and energy treatments
      included control, abomasal glucose infusion (382 g DM/d), or ruminal VFA infusion
      (150 g/d of acetic acid, 150 g/d of propionic acid, and 50 g/d of butyric acid).
      Leucine supplementation increased (P < 0.01) N retention, and energy
      supplementation tended to increase (P = 0.09) N retention without differences
      between glucose and VFA supplements (P = 0.86). Energy supplementation did not
      strikingly improve the efficiency of leucine utilization. Although both leucine
      and energy supplementation reduced urinary urea excretion (P <= 0.02), treatments
      did not affect urea production (P >= 0.34) or urea recycling to the gut (P >=
      0.30). The magnitude of change in protein deposition may have been too small to
      significantly affect urea kinetics. In Exp. 2, 6 steers (168 kg) were maintained
      in a model wherein methionine was the most limiting AA. Steers were placed in 2
      concurrent 3 * 3 Latin squares. Steers in one square were implanted with 24 mg of
      estradiol and 120 mg trenbolone acetate, and steers in the other square were not
      implanted. Treatments in each square were 0, 3, or 10 g/d of L-methionine.
      Implantation numerically improved N retention (P = 0.13) and reduced urea
      production rate (P = 0.03), urinary urea excretion (P < 0.01), and urea recycling
      to the gastrointestinal tract (P = 0.14). Effects of methionine were similar to
      implantation, but smaller in magnitude. When protein deposition by the body is
      increased markedly, ruminally available N in the diet may need to be increased to
      offset reductions in urea recycling.

PMID- 22851239
TI  - Effects of twenty percent corn wet distillers grains plus solubles in steam
      flaked and dry-rolled corn-based finishing diets on heifer performance, carcass
      characteristics, and manure characteristics.
AB  - Two hundred sixty-four crossbred heifers (initial BW = 354 kg +/- 0.5) were used
      to determine effects of corn processing method and wet distillers grains plus
      solubles (WDGS) inclusion in finishing diets on animal performance, carcass
      characteristics, and manure characteristics. The study was conducted as a
      randomized complete block with a 2 * 2 factorial arrangement of treatments.
      Dietary treatments included steam-flaked corn (SFC)- and dry-rolled corn (DRC)
      based finishing diets containing 0 or 20% WDGS (0SFC, 20SFC, 0DRC, and 20DRC,
      respectively). Heifers averaged 154 d on feed and were marketed in 3 groups.
      There were no interactions between corn processing method and WDGS detected (P >=
      0.29) for any performance or carcass response variables. Heifers fed diets
      containing WDGS tended to have greater final BW (P = 0.10) and increased G:F (P =
      0.08) compared with heifers fed diets without WDGS. Heifers fed SFC-based diets
      consumed 7% less feed (P < 0.01) and were 9% more efficient (P < 0.01) than
      heifers fed DRC-based diets. Carcass characteristics were not affected by corn
      processing method or WDGS inclusion (P >= 0.16). Intakes of OM, N, P, and K were
      greater (P <= 0.05) for heifers fed DRC-based diets than those fed SFC-based
      diets, which resulted in greater net accumulation of the nutrients in the manure
      (P <= 0.04). Heifers fed diets containing WDGS had greater (P < 0.01) intakes of
      N, P, and K than heifers fed diets without WDGS. As a result, a greater net
      accumulation of P and K (P <= 0.03) and N (P = 0.10) were present in the manure
      from cattle fed diets containing WDGS compared with those fed diets without WDGS.
      There was no interaction (P >= 0.16) between corn processing and WDGS on N
      volatilization losses. Nitrogen volatilization losses from manure (expressed as a
      percentage of intake and g.heifer(-1).d(-1)) were greater (P < 0.01) for heifers
      fed SFC-based diets than heifers fed DRC-based diets. Feeding DRC-based finishing
      diets to heifers resulted in increased manure production and nutrient excretion
      and decreased N volatilization. Both corn processing method and WDGS inclusion
      affected animal performance and manure characteristics.

PMID- 22851240
TI  - Effects of postmortem calcium chloride injection on meat palatability traits of
      strip loin steaks from cattle supplemented with or without zilpaterol
      hydrochloride.
AB  - An experiment was conducted to determine the effects of zilpaterol hydrochloride
      mM supplementation (ZH; 8.3 mg/kg on a DM basis for 20 d) and calcium chloride
      injection [CaCl(2), 200 at 5% (wt/wt) at 72 h postmortem] on palatability traits
      of beef (Bos taurus) strip loin steaks. Select (USDA) strip loins were obtained
      from control (no ZH = 19) and ZH-supplemented carcasses (n = 20). Right and left
      sides were selected alternatively to serve as a control (no INJ) or CaCl(2)
      injected (INJ) and stored at 4 degrees C. Before injecting the subprimals (72 h
      postmortem), 2 steaks were cut for proximate, sarcomere length, and myofibrillar
      fragmentation index (MFI) analyses. At 7 d postmortem each strip loin was
      portioned into steaks, vacuum packaged, and aged for the appropriate period for
      Warner-Bratzler shear force (WBSF; 7, 14, 21, and 28 d postmortem), trained
      sensory analysis (14 and 21 d postmortem), purge loss (7 d), and MFI (3, 7, 14,
      21, and 28 d postmortem). Results indicated steaks from both ZH supplementation
      and INJ had reduced WBSF values as days of postmortem aging increased. The WBSF
      values of ZH steaks were greater (P < 0.05) than no ZH steaks at each postmortem
      aging period. The INJ steaks had lower WBSF values (P < 0.05) than non-injected
      steaks. A greater percentage (91 vs. 71%) of steaks had WBSF values < 4.6 kg from
      steers with no ZH supplementation at 7 d postmortem, but the percentage did not
      differ (P > 0.05) due to ZH at 14, 21, or 28 d or due to INJ at any aging period.
      Trained panelists rated tenderness less in ZH steaks than steaks with no ZH at 14
      d and 21 d. However, INJ improved (P < 0.05) the tenderness ratings and flavor
      intensity of the trained panelists, compared with their non-injected cohorts at
      21 d. Zilpaterol hydrochloride supplementation reduced (P < 0.05) MFI values, but
      INJ resulted in greater (P < 0.05) MFI values compared with no INJ. Subprimals
      from ZH and INJ showed greater purge loss (P < 0.05). Although no interactions
      were found with ZH and CaCl(2), injecting USDA Select strip loins from ZH-fed
      cattle can help reduce the normal WBSF variation as it does in steaks from non-ZH
      fed cattle.

PMID- 22851241
TI  - Effects of pine bark supplementation on performance, rumen fermentation, and
      carcass characteristics of Kiko crossbred male goats.
AB  - Twenty-two Kiko crossbred male goats (Capra hircus; initial BW = 27.5 +/- 1.04
      kg) were used in a randomized complete block design to determine the effects of
      feeding pine bark (PB; Pinus taeda L.) on animal performance, rumen fermentation,
      blood parameters, fecal egg counts (FEC), and carcass characteristics in goats.
      Experimental treatments included the control diet [0% PB plus 30% wheat straw
      (WS)], 15% PB plus 15% WS, and 30% PB plus 0% WS (on as-fed basis), where PB
      replaced WS. Freshly air-dried PB and WS were finely (1.5 to 3.0 mm) ground and
      incorporated in the grain mixes. Experimental diets provided a total of 1.9,
      16.3, and 32 g of condense tannins (CT)/kg DM in 0%, 15%, and 30% PB diets,
      respectively. The grain mixes were fed daily at 85% of the feed offered, with
      remaining 15% consisting of Bermuda grass hay (Cynodon dactylon). Animals were
      fed once a day at 0800 h, and feed offered and refused was monitored for an 83-d
      performance period. Rumen and blood samples were collected at d 0, 50, and 80 of
      the study. Carcass traits were assessed after slaughter at the end of performance
      period. There was no difference in initial BW, hay, and total NDF intake among
      treatments; however, final BW (P = 0.06), ADG (P < 0.01), grain mix intake (P <
      0.001), total DMI (P < 0.001), and G:F (P < 0.04) increased linearly as the PB
      increased in the diets. Rumen ammonia N, acetate, isovalerate and acetate-to
      propionate ratio were reduced linearly (P < 0.05). There was no difference in
      carcass traits except cold carcass weight (P = 0.06), which tended to increase
      linearly in goats fed 15% and 30% PB. Breast, sirloin, trim trait, liver, and
      hide weight increased (linear; P < 0.01) with addition of PB. Blood basophils,
      alanine transaminase, aspartate aminotransferase, albumin, Na, and Cl
      concentrations decreased (linear; P < 0.02 to 0.01) as PB supplementation
      increased. Supplementation of PB reduced (linear; P < 0.01) average FEC. Addition
      of PB in the diets improved performance, reduced FEC, and favorably modified
      rumen fermentation.

PMID- 22851242
TI  - Effects of ruminal casein and glucose on forage digestion and urea kinetics in
      beef cattle.
AB  - Effects of supplemental glucose and degradable intake protein on nutrient
      digestion and urea kinetics in steers (Bos taurus) given ad libitum access to
      prairie hay (4.7% CP) were quantified. Six ruminally and duodenally cannulated
      steers (initial BW 391 kg) were used in a 4 * 4 Latin square with 2 extra steers.
      Treatments were arranged as a 2 * 2 factorial and included 0 or 1.2 kg of glucose
      and 240 or 480 g of casein dosed ruminally once daily. Each period included 9 d
      for adaptation, 4 d for total fecal and urine collections, and 1 d for ruminal
      and duodenal sampling. Jugular infusion of (15)N(15)N-urea with measurement of
      enrichment in urine was used to measure urea kinetics. Glucose reduced forage
      intake by 18% (P < 0.01), but casein did not affect forage intake (P = 0.69).
      Glucose depressed (P < 0.01) total tract NDF digestion. Glucose supplementation
      decreased ruminal pH 2 h after dosing, but the effect was negligible by 6 h
      (treatment * time; P = 0.01). Providing additional casein increased the ruminal
      concentration of NH(3), but the increase was less when glucose was supplemented
      (casein * glucose; P < 0.01). Plasma urea-N was increased (P < 0.01) by
      additional casein but was reduced (P < 0.01) by glucose. Microbial N flow to the
      duodenum and retained N increased (P <= 0.01) as casein increased, but neither
      was affected by glucose supplementation. Urea-N entry rate increased (P = 0.03)
      50% with increasing casein. Urinary urea-N excretion increased (P < 0.01) as
      casein increased. The proportion of urea production that was recycled to the gut
      decreased (P < 0.01) as casein increased. Glucose supplementation decreased (P <
      0.01) urinary urea excretion but did not change (P >= 0.70) urea production or
      recycling. The amount of urea-N transferred to the gut and captured by ruminal
      microbes was less for steers receiving 480 g/d casein with no glucose than for
      the other 3 treatments (casein * glucose interaction, P = 0.05), which can be
      attributed to an excess of ruminally available N provided directly to the
      microbes from the supplement. Overall, the provision of supplemental glucose
      decreased forage intake and digestibility. Increasing supplemental casein from
      240 to 480 g/d increased urea production but decreased the proportion of urea-N
      recycled to the gut.

PMID- 22851243
TI  - Serum metabolites, milk yield, and physiological responses during the first week
      after kidding in Anglo-Nubian, Angora, Baladi, and Damascus goats under
      subtropical conditions.
AB  - This study was carried out to determine the level of certain biochemical
      variables reflecting the energy metabolic statuses during the first week of
      lactation in goats. A total of 120 Anglo-Nubian, Angora, Baladi, and Damascus
      does (30 does per breed) were used throughout 5 consecutive parities (30 does per
      parity) to investigate the effect of breed, parity, day of lactation, and their
      interaction on serum metabolites including total protein, albumin, globulin,
      glucose, total lipids, cholesterol, and transaminases. Blood samples were
      collected every other day during the first week of lactation. Baladi does had the
      greatest (P < 0.001) values in all measured biochemical variables followed by
      Anglo-Nubian [in total protein, globulin, and aminotransferase (AST)] and
      Damascus (in globulin and AST) and then Angora, which had the lowest (P < 0.001)
      values for all variables. Fifth parity exhibited the greatest (P < 0.001) values
      in all serum metabolites compared with other parities except for alanine
      transaminase (ALT) enzyme activity in which the greatest (P = 0.046) values were
      observed in the first and fourth parties. Serum concentrations of the measured
      variables increased gradually throughout the first day after kidding until the
      seventh day for total protein (P < 0.001), albumin (P = 0.013), globulin (P =
      0.017), and cholesterol (P = 0.028) whereas serum glucose concentration exhibited
      an opposite trend. Serum concentrations of total lipids and enzyme activities of
      AST and ALT were not affected by day (P > 0.05) after kidding. Baladi goats had
      the least (P < 0.001) serum insulin concentration, which was associated (P <
      0.001) with greatest serum glucose concentration. Serum triiodothyronine (T(3))
      was inversely correlated (P = 0.032) with milk yield whereas greatest (P = 0.003)
      T(3) concentrations were associated with least (P < 0.001) milk yield recorded in
      Angora goats. Animal physiological responses and their indices were not affected
      (P > 0.05) by breed whereas both rectal temperature and coefficient of heat
      tolerance were affected (P < 0.001) by parity in an opposite direction. Baladi
      goats expressed an aspect of adaptability where their rectal temperature
      decreased and coefficient of heat tolerance increased with increasing parity
      number.

PMID- 22851244
TI  - Ileal amino acid digestibility in canola meals from yellow- and black-seeded
      Brassica napus and Brassica juncea fed to growing pigs.
AB  - Twelve ileal cannulated pigs (30.9 +/- 2.7 kg) were used to determine the
      apparent (AID) and standardized (SID) ileal digestibility of protein and AA in
      canola meals (CM) derived from black- (BNB) and yellow-seeded (BNY) Brassica
      napus canola and yellow-seeded Brassica juncea (BJY). The meals were produced
      using either the conventional pre-press solvent extraction process (regular meal)
      or a new, vacuum-assisted cold process of meal de-solventization (white flakes)
      to provide 6 different meals. Six cornstarch-based diets containing 35% canola
      meal as the sole source of protein in a 3 (variety) * 2 (processing) factorial
      arrangement were randomly allotted to pigs in a 6 * 7 incomplete Latin square
      design to have 6 replicates per diet. A 5% casein diet was fed to estimate
      endogenous AA losses. Canola variety and processing method interacted for the AID
      of DM (P = 0.048), N (P = 0.010), and all AA (P < 0.05), except for Arg, Lys,
      Phe, Asp, Glu, and Pro. Canola variety affected or tended to affect the AID of
      most AA but had no effect on the AID of Lys, Met, Val, Cys, and Pro, whereas
      processing method had an effect on only Lys and Asp and tended to affect the AID
      of Thr, Gly and Ser. The effects of canola variety, processing method, and their
      interaction on the SID values for N and AA followed a similar pattern as for AID
      values. For the white flakes, SID of N in BJY (74.2%) was lower than in BNY and
      BNB, whose values averaged 78.5%; however, among the regular meals, BJY had a
      greater SID value for N than BNY and BNB (variety * processing, P = 0.015). For
      the white flakes, the SID of Ile (86.4%), Leu (87.6%), Lys (88.9%), Thr (87.6%)
      and Val (84.2%) in BNB were greater than BNY and BJY. Opposite results were
      observed for the regular processing, with SID of Lys (84.1%), Met (89.5%), Thr
      (84.1%), and Val (83.6%) being greater in BJY, followed by BNB and BNY(variety *
      processing, P < 0.057). The SID of Met was greatest for the white flakes (90.2%)
      but least for the regular processing (83.0%) in BNY (variety * processing, P <
      0.057). It was concluded that the AID and SID of N and AA of the CM tested varied
      according to canola variety and the processing method used. Overall, the SID
      values for Ile, Leu, Lys, Met, Thr, and Val averaged across CM types and
      processing methods were 81.8, 82.6, 83.4, 85.9, 80.8, and 78.4%, respectively.

PMID- 22851245
TI  - Parentage verification in field progeny testing program of Mehsana buffalo.
AB  - The present study was undertaken to construct a multiplex microsatellite panel
      for parentage testing in Mehsana buffalo (Bubalus bubalis). The study was based
      on a total of 212 Mehsana buffalos (100 dams, 100 daughters, and 12 sires).
      Genomic DNA was extracted from blood and semen samples. A panel of 10
      microsatellite markers (CSSM61, ILSTS29, ILSTS17, ILSTS28, CSSM57, CSSM22,
      ILSTS61, CSSM8, ETH152, and ILSTS11) was amplified in a single multiplex reaction
      and analyzed by capillary electrophoresis on an automated DNA sequencer. The
      expected heterozygosity ranged from 0.642 to 0.833 (mean 0.762). The total
      exclusion probability using 10 microsatellite loci with 1 known parent was 0.993.
      Seven out of 10 microsatellite loci revealed relatively high polymorphic
      information content (>0.7). Eighty-one daughters out of 100 daughters qualified
      by compatibility according to Mendelism. The results suggest that multiplex
      microsatellite panel is a fast, robust, reliable, and economic tool to verify the
      parentage as well as to assign the putative sire to daughters under progeny
      testing with very high accuracy and hence can be used in routine parentage
      testing.

PMID- 22851246
TI  - Impact of distillers dried grains with solubles particle size on nutrient
      digestibility, DE and ME content, and flowability in diets for growing pigs.
AB  - A study was conducted to determine the effect of particle size of distillers
      dried grains with solubles (DDGS) on DE and ME content, diet DM, energy, N, P
      digestibility, and diet flowability for growing pigs. One DDGS source was
      processed through an Urshel Commitrol mill or a hammer mill to achieve mean
      particle sizes of 818, 595, and 308 MUm. The basal control diet consisted of
      96.8% corn with supplemental minerals and vitamins. Three experimental diets were
      formulated by replacing 30% of corn from the basal diet with DDGS of different
      particle sizes. Thirty-six growing pigs (initial BW of 40 +/- 1.13 kg) were
      assigned to 1 of 4 treatments in a randomized complete block design according to
      their BW block and housed in individual metabolic crates for a 9-d adaptation
      period followed by a 4-d total collection of feces and urine. Pigs were provided
      ad libitum access to water and fed an amount of their respective experimental
      diets equivalent to 3% of the initial BW of each pig. Feed, feces, and urine
      samples were analyzed for DM, GE, N, and P and used to calculate diet apparent
      total tract digestibility (ATTD). Gross energy was also used to calculate DE and
      ME of diets as well as the DE and ME content of corn and DDGS with different
      particle sizes. Diet drained and poured angles of repose were measured using a
      modified Hele-Shaw cell method to evaluate the diet flowability. Inclusion of 30%
      DDGS with an average particle size of 308 MUm improved (P < 0.05) dietary ATTD of
      DM and GE as well as DE (4,006 vs. 3,783 kcal/kg DM) and ME (3,861 vs. 3,583
      kcal/kg DM) compared with 818 MUm DDGS. No differences (P > 0.05) were found in N
      and P digestibility among the 3 DDGS diets. The DDGS particle size of 595 MUm had
      greater (P < 0.05) DE but not ME compared with 818 MUm DDGS, and DE and ME were
      not different between 308 and 595 MUm. Compared with a 595 or 818 MUm DDGS,
      grinding DDGS to 308 MUm reduced diet flowability as indicated by a greater (P <
      0.05) drained angle of repose. These results suggested that for each 25 MUm
      decrease in DDGS particle size from 818 MUm to 308 MUm, the ME contribution of
      DDGS to the diet is 13.46 kcal/kg DM, but diet flowability will be reduced.

PMID- 22851247
TI  - Effects of supplemental energy and protein on forage digestion and urea kinetics
      in growing beef cattle.
AB  - Effects of supplemental energy sources on nutrient digestion and urea kinetics at
      2 levels of degradable intake protein were evaluated in cattle (Bos taurus). Six
      ruminally and duodenally cannulated steers (208 +/- 17 kg) were used in a 6 * 6
      Latin square with treatments arranged as a 3 * 2 factorial. Energy treatments
      included a control, 600 g glucose dosed ruminally once daily, and 480 g VFA
      infused ruminally over 8 h daily. Casein (120 or 240 g) was dosed ruminally once
      daily. Steers had ad libitum access to prairie hay (5.8% CP). Jugular infusion of
      (15)N(15)N-urea with measurement of enrichment in urine was used to measure urea
      kinetics. Infusing VFA decreased (P < 0.01) forage intake by 27%. Supplementing
      glucose decreased (P < 0.01) total tract NDF digestibility and tended to decrease
      ruminal NDF digestibility; depressions in response to glucose tended to be
      greater at the lower level of casein. Increasing casein decreased (P < 0.02)
      ruminal pH. Infusing VFA decreased pH only during infusions, whereas glucose
      decreased pH 2 h after dosing. Ruminal concentrations of NH(3), acetate, and
      propionate decreased and butyrate concentration increased when glucose was
      supplemented. Increasing casein supplementation increased (P < 0.01) ruminal
      concentrations of NH(3), acetate, and propionate. Supplemental energy decreased
      (P = 0.03) plasma urea-N concentration, but casein level did not affect it (P =
      0.16). Microbial N flow was greater (P < 0.04) for 240 than for 120 g/d casein
      but was not affected by supplemental energy (P = 0.23). Urea-N entry rate and gut
      entry of urea-N were not affected (P >= 0.12) by supplemental energy or casein,
      but the proportion of urea production that was recycled to the gut was less (P =
      0.01) when 240 g/d rather than 120 g/d casein was provided. Compared with VFA,
      glucose tended (P = 0.07) to increase the proportion of urea-N entry rate that
      was recycled to the gut. Supplementation with glucose led to more (P = 0.01)
      microbial uptake of recycled urea than did supplementation with VFA. Urea
      recycling did not differ greatly among treatments despite impacts on ruminal pH
      and NH(3) and on plasma urea-N that were expected to alter urea transport across
      ruminal epithelium. Lack of treatment effects on urea production indicate that
      the complete diets did not provide excessive amounts of N and that increases of
      intestinally available AA were used efficiently by cattle for protein deposition.

PMID- 22851248
TI  - Supplemental palmitoleic (C16:1 cis-9) acid reduces lipogenesis and desaturation
      in bovine adipocyte cultures.
AB  - Our objective was to determine if palmitoleic (C16:1 cis-9) acid supplementation
      to primary bovine adipocytes regulates lipogenic gene expression and rates of
      lipogenesis. Stromal vascular cells were isolated from subcutaneous and
      intermuscular fat, propagated, and frozen for use in this study. Cells were
      passaged 4 times, allowed to reach confluence, held for 2 d, and then
      differentiated with a standard hormone cocktail (d 0). At d 2, secondary
      differentiation media containing 1 of 4 concentrations of palmitoleic acid (0,
      50, 150, or 300 MUM) were added for 10 d. Cells were harvested on d 6 and 12 to
      assess fatty acid concentrations and gene expression. In addition, (13)C2 and
      (13)C18:0 stable isotopes were added on d 6 to measure lipogenesis and desaturase
      activity, respectively. Concentrations of C16:1 and total fatty acids increased
      (P < 0.05) linearly in response to palmitoleic acid supplement. Concentrations of
      C18:1 cis-11 and C20:1 cis-13 also increased (P < 0.01) in response to
      supplementation, suggesting elongation of palmitoleic acid in vitro.
      Concentrations of C16:1, C18:1 cis-11, and total fatty acids were also greater (P
      < 0.05) at d 12 compared with d 6. In contrast, C16:0, C18:0, and C18:1 cis-9
      concentrations decreased (P < 0.05) in response to palmitoleic acid
      supplementation and were not affected (P > 0.05) by harvest day. The ratio of
      C18:1 cis-9/C18:0 and fractional synthetic rate (FSR) of desaturation decreased
      (P < 0.05) in response to increasing palmitoleic acid supplementation. In
      addition, FSR of lipogenesis was reduced (P < 0.05) in palmitoleic acid-treated
      cells. Messenger RNA abundance as determined by real-time quantitative PCR for
      stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FASN), and elongase
      protein 6 (ELOVL6) genes were reduced (P < 0.05) by palmitoleic acid
      supplementation. Expression of a beta-oxidation gene, carnitine
      palmitoyltransferase 1A (CPT1A), was upregulated (P < 0.05) with palmitoleic acid
      supplementation in a dose-responsive manner. Supplementation of palmitoleic acid
      to bovine adipocytes results in increased incorporation of this fatty acid and
      its elongation products into the adipocyte, which downregulates SCD1, FASN, and
      ELOVL6 to decrease lipogenesis and upregulates CPT1A, potentially increasing beta
      oxidation. These results suggest that palmitoleic acid, an end product of
      desaturation, can act as a regulator of lipogenesis, desaturation, and beta
      oxidation in bovine adipocytes.

PMID- 22851250
TI  - Immune system stimulation reduces the efficiency of tryptophan utilization for
      body protein deposition in growing pigs.
AB  - The effect of immune system stimulation (ISS) on N retention and Trp utilization
      in pigs fed Trp-limiting diets was evaluated using 36 growing pigs (20.0 +/- 1.1
      kg BW; 3 blocks of 12 barrows). Pigs were randomly assigned to 1 of 5 diets (Diet
      1, 2, 4, and 5, n = 7; Diet 3, n = 8) and fed restrictively at 800 g/d. Diets 1
      to 4 were generated by blending Diet 1 with a protein-free supplement and were
      calculated to contain varying amounts of standardized ileal digestible (SID) Trp
      (1.31, 1.05, 0.80, and 0.55 g/kg). To confirm that Trp was the first-limiting AA
      in Diets 1 to 4, an additional diet was used (Diet 5), which was equivalent to
      Diet 4 and contained 0.34 g/kg of added Trp. After a 5-d adaptation period, pigs
      were injected every 2 d with increasing amounts of E. coli lipopolysaccharide to
      induce ISS (initial dose 20 MUg/kg BW, increasing 15% each subsequent injection).
      Whole body N balance was measured in 3 periods: before immune stimulation (pre
      ISS) and during ISS in 2 subsequent periods (ISS-1, 3 d; ISS-2, 4 d). Regression
      analysis was used to estimate the marginal efficiency of Trp utilization for
      whole body protein deposition (PD; N retention * 6.25). Plasma concentrations of
      acute-phase proteins and white blood cell counts increased (P < 0.001) and plasma
      albumin decreased (P < 0.001) during ISS. Nitrogen retention increased (P <
      0.001) as Trp intake increased. Nitrogen retention was numerically greater but
      not statistically different between Diet 5 (added Trp diet) and Diet 4. Whole
      body N retention was less (P < 0.05) during ISS due primarily to an increase (P <
      0.05) in urinary N excretion. There was a linear response (P < 0.05) in N
      retention, urinary N, and total excreted N to increasing Trp intake. Protein
      deposition increased by 88.2 +/- 5.2, 82.5 +/- 5.1, and 92.5 +/- 3.4 g/d for each
      additional g/d of SID Trp intake during pre-ISS, ISS-1, and ISS-2, respectively,
      but the intercept was not different (-32.3 g/d). The slope of the response of PD
      to increasing Trp intake (based on the common intercept) was less during ISS-1
      compared with pre-ISS (P = 0.01) or ISS-2 (P = 0.002) but not different between
      pre-ISS and ISS-2. Immune system stimulation reduced N retention in pigs fed
      limiting dietary Trp. The efficiency of Trp utilization for protein deposition
      was also reduced during ISS, indicating that the Trp requirement for PD is
      increased ~7% during an inflammatory state.

PMID- 22851249
TI  - Effects of oxidized corn oil and a synthetic antioxidant blend on performance,
      oxidative status of tissues, and fresh meat quality in finishing barrows.
AB  - The objective was to evaluate the effect of feeding oxidized corn oil with or
      without a dietary antioxidant (AOX) on performance, tissue oxidative status, and
      meat quality in barrows. One hundred sixty barrows were arranged in a 2 * 2
      factorial of treatments in a complete randomized block design with 8 pens per
      treatment and 5 pigs per pen. Diets contained 5.0 mg/kg of 1 of 2 types of corn
      oil (fresh or oxidized) with or without antioxidant. Final oxidized oil was
      produced in a heated container by continuously bubbling air heated to 95 degrees
      C at a rate of 80 L/min to reach a target peroxide value of approximately 150 and
      7.5 mEq/kg in the final diet. After 56 d, barrows fed diets formulated with fresh
      oil had increased ADG (P = 0.03) and ADFI (P = 0.04) and heavier final BW (P =
      0.03) than barrows fed oxidized oil. Increased G:F (P = 0.07) was observed for
      barrows fed diets with AOX after 28 d of feeding but not after 56 d of feeding (P
      = 0.67) when compared with barrows not fed AOX. An increase (P = 0.06) in plasma
      thiobarbituric acid reactive substances (TBARS) values, a decrease (P = 0.03) in
      plasma glutathione peroxidase (GPx) enzyme activity, and a decrease (P = 0.01) in
      liver vitamin E concentrations were observed in barrows fed diets with oxidized
      oil. Dietary AOX reduced plasma protein carbonyl content regardless of oil type
      (P = 0.04). Barrows fed fresh oil had 4.4% heavier HCW (P = 0.01) and 0.7
      percentage units increase in dressing percentage (P = 0.01) compared with barrows
      fed oxidized oil. Loin TBARS values from barrows fed AOX were lower (P < 0.001)
      after 14 and 21 d of storage in both fresh and oxidized oil groups. In summary,
      oxidized oil impaired growth performance and caused oxidation stress. Dietary AOX
      partially ameliorated the negative effects of oxidized oil in finishing pigs by
      reducing protein oxidation and improving shelf life.

PMID- 22851251
TI  - Up to 30% corn germ may be included in diets fed to growing-finishing pigs
      without affecting pig growth performance, carcass composition, or pork fat
      quality.
AB  - A total of 280 pigs (initial BW: 42.5 +/- 4.6 kg) were used to determine effects
      of adding corn germ (15.6% CP; 16.6% acid hydrolyzed ether extract; 21.7% NDF) to
      diets fed to growing-finishing pigs. Pigs were ransssdomly allotted to 1 of 8
      dietary treatments in a 2 * 4 factorial arrangement of treatments with 2 levels
      of distillers dried grains with solubles (DDGS; 0 or 30%) and 4 levels of corn
      germ (0, 10, 20, or 30%). Each diet was fed to 10 pens with either 3 or 4 pigs
      per pen. Pigs were fed phase 1, 2, and 3 diets for 28, 28, and 27 d,
      respectively. At the conclusion of the experiment, 1 pig in each pen that had a
      BW that was closest to the average BW for the pen was harvested. For the overall
      experimental period, regardless of the level of DDGS, there was no effect of corn
      germ on pig growth performance, but inclusion of 30% DDGS in the diet reduced (P
      < 0.001) ADG, ADFI, and final BW. There were no effects of corn germ on carcass
      composition, muscle quality, or fat quality, but LM marbling and firmness were
      reduced (P < 0.05) by inclusion of DDGS in the diet. The L* value of LM decreased
      (linear and quadratic; P < 0.05) as corn germ was included in diets containing no
      DDGS, but that was not the case when corn germ was added to diets containing 30%
      DDGS (corn germ * DDGS; P < 0.01). Inclusion of DDGS in the diet reduced (P <
      0.001) the L* value for backfat, but there were no effects of corn germ on
      backfat color measures. Inclusion of corn germ in diets containing no DDGS
      increased belly length (quadratic; P < 0.05), but that was not observed if corn
      germ was added to diets containing 30% DDGS. There was also a decrease in belly
      flop distance as corn germ was added to diets containing no DDGS (linear; P <
      0.001), but no effects of corn germ were observed in diets containing 30% DDGS.
      However, inclusion of DDGS in the diet reduced (P < 0.001) the belly flop
      distance. In conclusion, addition of up to 30% corn germ in diets containing 0 or
      30% DDGS did not negatively affect pig growth performance, carcass composition,
      or muscle quality, but belly firmness was reduced.

PMID- 22851252
TI  - Role of the backbone conformation at position 7 in the structure and activity of
      marinostatin, an ester-linked serine protease inhibitor.
AB  - Rational design of inhibitors: The cis-amide backbone at position 7 in the serine
      protease inhibitor marinostatin was replaced with an E or Z olefin. The E olefin
      analogue was not active, but the Z analogue was. The cis conformation might play
      a critical role in organizing a canonical structure for binding to proteases.

PMID- 22851253
TI  - Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes
      indicate potential oncogenic influences of human papillomavirus in prostate
      cancer.
AB  - INTRODUCTION: The purpose of this study is to determine if high risk human
      papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same
      prostate cancer specimens. METHODS: We used a range of analytical techniques
      including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR
      followed by sequencing of the product to seek to identify HPV and EBV in normal,
      benign, and malignant prostate tissues. RESULTS: Both HPV type 18 and EBV gene
      sequences were identified in a high and approximately equal proportion of normal,
      benign, and prostate cancer specimens. These sequences were located in the nuclei
      of prostate epithelial cells. HPV associated koilocytes were identified in 24% of
      prostate cancer specimens. CONCLUSIONS: The presence of both HPV and EBV gene
      sequences in most of the same normal, benign, and malignant prostate specimens is
      particularly noteworthy because of recent experimental evidence demonstrating
      that EBV and HPV can collaborate to increase proliferation of cultured cervical
      cells. Because the presence of EBV and HPV in normal, benign, and malignant
      prostate tissues appears to be ubiquitous, it is possible that they are harmless.
      On the other hand HPV type 18 in particular, has high oncogenic potential and may
      be associated with some prostate cancers. The identification of HPV associated
      koilocytes in prostate cancer specimens is an indication of HPV infection and
      potential oncogenic influences of human papillomavirus in prostate cancer.

PMID- 22851254
TI  - SMT: a reliability based interactive DTI tractography algorithm.
AB  - Tractography refers to the in vivo reconstruction of fiber bundles, e.g., in
      brain, via the analysis of anisotropic diffusion patterns measured by diffusion
      weighted magnetic resonance imaging (DWI). The data provides a probabilistic
      model of local diffusion which was shown to correlate with the underlying fibrous
      structure under certain assumptions. Deterministic tractography suffers from
      uncertainties at kissing and crossing fibers, at different levels depending on
      the diffusion model employed (e.g., DTI, HARDI), yet it is easy to interpret and
      use in clinic. In this study, a novel generic algorithm, split and merge
      tractography (SMT), is proposed that provides a real-time, interactive and
      reliability ranked assessment of potential pathways, communicating the true
      information content of the data without sacrificing the usability of
      tractography. Specifically, SMT takes in a precomputed set of tracts and the
      diffusion data (e.g., DTI, HARDI) as its input, generates a set of short
      (reliable) tracts via splitting at unreliable points and forms quasi-random
      clusters of short tracts by means of which the space of short tract clusters,
      representing complete tracts, is sampled. A histogram of thus formed clusters is
      built in an efficient way and used for real-time, interactive assessment of
      pathways. The current implementation uses DTI and fourth-order Runge-Kutta
      integration based streamline tractography as its input. The method is
      qualitatively assessed on phantom DTI data and real DTI data. Phantom experiments
      demonstrated that SMT is capable of highlighting the problematic regions and
      suggesting pathways that are completely overseen by input streamline
      tractography. Real data experiment results correlate well with known anatomy and
      also demonstrate that the reliability ranking can efficiently suppress the
      erroneous tracts interactively. The method is compared to a recent method that
      also pursues a similar approach, yet in a global optimization based framework.
      The comparative study on real DTI data revealed the lower computational load of
      SMT and a better correlation with known anatomy.

PMID- 22851255
TI  - ADHD and autism: differential diagnosis or overlapping traits? A selective
      review.
AB  - According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome
      precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD).
      However, despite the different conceptualization, population-based twin studies
      reported symptom overlap, and a recent epidemiologically based study reported a
      high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned
      revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic
      disorder and ADHD will not be mutually exclusive any longer. This provides the
      basis of more differentiated studies on overlap and distinction between both
      disorders. This review presents data on comorbidity rates and symptom overlap and
      discusses common and disorder-specific risk factors, including recent proteomic
      studies. Neuropsychological findings in the areas of attention, reward
      processing, and social cognition are then compared between both disorders, as
      these cognitive abilities show overlapping as well as specific impairment for one
      of both disorders. In addition, selective brain imaging findings are reported.
      Therapeutic options are summarized, and new approaches are discussed. The review
      concludes with a prospectus on open questions for research and clinical practice.

PMID- 22851257
TI  - Adaptive Kalman filtering for histogram-based appearance learning in infrared
      imagery.
AB  - Targets of interest in video acquired from imaging infrared sensors often exhibit
      profound appearance variations due to a variety of factors, including complex
      target maneuvers, ego-motion of the sensor platform, background clutter, etc.,
      making it difficult to maintain a reliable detection process and track lock over
      extended time periods. Two key issues in overcoming this problem are how to
      represent the target and how to learn its appearance online. In this paper, we
      adopt a recent appearance model that estimates the pixel intensity histograms as
      well as the distribution of local standard deviations in both the foreground and
      background regions for robust target representation. Appearance learning is then
      cast as an adaptive Kalman filtering problem where the process and measurement
      noise variances are both unknown. We formulate this problem using both covariance
      matching and, for the first time in a visual tracking application, the recent
      autocovariance least-squares (ALS) method. Although convergence of the ALS
      algorithm is guaranteed only for the case of globally wide sense stationary
      process and measurement noises, we demonstrate for the first time that the
      technique can often be applied with great effectiveness under the much weaker
      assumption of piecewise stationarity. The performance advantages of the ALS
      method relative to the classical covariance matching are illustrated by means of
      simulated stationary and nonstationary systems. Against real data, our results
      show that the ALS-based algorithm outperforms the covariance matching as well as
      the traditional histogram similarity-based methods, achieving sub-pixel tracking
      accuracy against the well-known AMCOM closure sequences and the recent SENSIAC
      automatic target recognition dataset.

PMID- 22851256
TI  - Updates in the treatment of spasticity associated with cerebral palsy.
AB  - OPINION STATEMENT: Spasticity affects up to 80 % of patients with cerebral palsy
      (CP) and often plays a significant role in limiting the child's ability to
      function and participate in daily activities. The treatment of spasticity
      involves a multifaceted approach that includes pharmacological treatment with
      antispasmodics, physical therapy to maintain range of motion and prevent
      contractures, as well as a variety of orthopedic and neurosurgical interventions.
      Pharmacological agents currently used in clinical practice to treat spasticity in
      children have existed for almost two decades and continue to be used despite lack
      of solid evidence for their efficacy. Studies detailing safety profiles and
      optimal dosing in the pediatric population are greatly warranted. Intramuscular
      injection of botulinum neurotoxin is becoming increasingly popular for the
      treatment of segmental spasticity and current literature suggests it is safe and
      effective (Level A). Constraint-induced movement therapy (CIMT) and repetitive
      transcranial magnetic stimulation (rTMS) are emerging as effective interventions
      in improving motor function in hemiplegic CP. However, the role of these as of
      yet >interventions in reducing spasticity remains to be clarified.

PMID- 22851258
TI  - Automatic dynamic texture segmentation using local descriptors and optical flow.
AB  - A dynamic texture (DT) is an extension of the texture to the temporal domain. How
      to segment a DT is a challenging problem. In this paper, we address the problem
      of segmenting a DT into disjoint regions. A DT might be different from its
      spatial mode (i.e., appearance) and/or temporal mode (i.e., motion field). To
      this end, we develop a framework based on the appearance and motion modes. For
      the appearance mode, we use a new local spatial texture descriptor to describe
      the spatial mode of the DT; for the motion mode, we use the optical flow and the
      local temporal texture descriptor to represent the temporal variations of the DT.
      In addition, for the optical flow, we use the histogram of oriented optical flow
      (HOOF) to organize them. To compute the distance between two HOOFs, we develop a
      simple effective and efficient distance measure based on Weber's law.
      Furthermore, we also address the problem of threshold selection by proposing a
      method for determining thresholds for the segmentation method by an offline
      supervised statistical learning. The experimental results show that our method
      provides very good segmentation results compared to the state-of-the-art methods
      in segmenting regions that differ in their dynamics.

PMID- 22851259
TI  - Nonlinearity detection in hyperspectral images using a polynomial post-nonlinear
      mixing model.
AB  - This paper studies a nonlinear mixing model for hyperspectral image unmixing and
      nonlinearity detection. The proposed model assumes that the pixel reflectances
      are nonlinear functions of pure spectral components contaminated by an additive
      white Gaussian noise. These nonlinear functions are approximated by polynomials
      leading to a polynomial post-nonlinear mixing model. We have shown in a previous
      paper that the parameters involved in the resulting model can be estimated using
      least squares methods. A generalized likelihood ratio test based on the estimator
      of the nonlinearity parameter is proposed to decide whether a pixel of the image
      results from the commonly used linear mixing model or from a more general
      nonlinear mixing model. To compute the test statistic associated with the
      nonlinearity detection, we propose to approximate the variance of the estimated
      nonlinearity parameter by its constrained Cramer-Rao bound. The performance of
      the detection strategy is evaluated via simulations conducted on synthetic and
      real data. More precisely, synthetic data have been generated according to the
      standard linear mixing model and three nonlinear models from the literature. The
      real data investigated in this study are extracted from the Cuprite image, which
      shows that some minerals seem to be nonlinearly mixed in this image. Finally, it
      is interesting to note that the estimated abundance maps obtained with the post
      nonlinear mixing model are in good agreement with results obtained in previous
      studies.

PMID- 22851260
TI  - High capacity data hiding for error-diffused block truncation coding.
AB  - Block truncation coding (BTC) is an efficient compression technique with
      extremely low computational complexity. However, the blocking and false contour
      effects are two major deficiencies in BTC which cause severe perceptual
      artifacts. The former scheme, error-diffused BTC (EDBTC), can significantly
      improve the above issues through the visual low-pass compensation on the bitmap,
      which thus widens its possible application market, yet the corresponding security
      issue may limit its value. In this paper, a method namely complementary hiding
      EDBTC is developed to cope the above issue. This paper is managed by firstly
      discussing when a single watermark is embedded, and then multiple watermarks are
      employed to test the limitation of the proposed scheme. Herein, an adaptive
      external bias factor is employed to control the watermark embedding, and this
      factor also affects the image quality and robustness simultaneously. Experimental
      results demonstrate that the proposed method only requires an extremely small
      external bias factor to carry watermarks, which enables a high capacity scenario
      without significantly damaging image quality.

PMID- 22851261
TI  - Compressive light field sensing.
AB  - We propose a novel design for light field image acquisition based on compressive
      sensing principles. By placing a randomly coded mask at the aperture of a camera,
      incoherent measurements of the light passing through different parts of the lens
      are encoded in the captured images. Each captured image is a random linear
      combination of different angular views of a scene. The encoded images are then
      used to recover the original light field image via a novel Bayesian
      reconstruction algorithm. Using the principles of compressive sensing, we show
      that light field images with a large number of angular views can be recovered
      from only a few acquisitions. Moreover, the proposed acquisition and recovery
      method provides light field images with high spatial resolution and signal-to
      noise-ratio, and therefore is not affected by limitations common to existing
      light field camera designs. We present a prototype camera design based on the
      proposed framework by modifying a regular digital camera. Finally, we demonstrate
      the effectiveness of the proposed system using experimental results with both
      synthetic and real images.

PMID- 22851262
TI  - Track creation and deletion framework for long-term online multiface tracking.
AB  - To improve visual tracking, a large number of papers study more powerful
      features, or better cue fusion mechanisms, such as adaptation or contextual
      models. A complementary approach consists of improving the track management, that
      is, deciding when to add a target or stop its tracking, for example, in case of
      failure. This is an essential component for effective multiobject tracking
      applications, and is often not trivial. Deciding whether or not to stop a track
      is a compromise between avoiding erroneous early stopping while tracking is fine,
      and erroneous continuation of tracking when there is an actual failure. This
      decision process, very rarely addressed in the literature, is difficult due to
      object detector deficiencies or observation models that are insufficient to
      describe the full variability of tracked objects and deliver reliable likelihood
      (tracking) information. This paper addresses the track management issue and
      presents a real-time online multiface tracking algorithm that effectively deals
      with the above difficulties. The tracking itself is formulated in a multiobject
      state-space Bayesian filtering framework solved with Markov Chain Monte Carlo.
      Within this framework, an explicit probabilistic filtering step decides when to
      add or remove a target from the tracker, where decisions rely on multiple cues
      such as face detections, likelihood measures, long-term observations, and track
      state characteristics. The method has been applied to three challenging data sets
      of more than 9 h in total, and demonstrate a significant performance increase
      compared to more traditional approaches (Markov Chain Monte Carlo, reversible
      jump Markov Chain Monte Carlo) only relying on head detection and likelihood for
      track management.

PMID- 22851263
TI  - Increase in serum 25-hydroxyvitamin-D3 in humans after solar exposure under
      natural conditions compared to artificial UVB exposure of hands and face.
AB  - Vitamin D studies are often performed under controlled laboratory conditions and
      the findings may be difficult to translate to natural conditions. We aimed to
      determine and compare the doses of natural solar ultraviolet radiation (UVR) with
      doses of artificial UVB radiation of hands and face needed to increase serum 25
      hydroxyvitamin-D(3) (25(OH)D). Furthermore, we aimed to investigate the natural
      course of 25(OH)D due to solar exposure from April to September. 46 Caucasian
      volunteers were included. 17 volunteers received solar UVR (Group 1) in their
      natural Danish environment. Individual daily solar UVR doses in standard erythema
      doses (SEDs) were determined with personal wristwatch UV-dosimeters. 29
      volunteers (Group 2) received artificial UVB doses of 6 SEDs (N = 14) and 3 SEDs
      (N = 15) on hands and face during late-winter/early-spring when outdoor UVB is
      negligible. 25(OH)D-levels were determined around every second week during study
      periods. Solar-UVR doses and sun-exposure diaries with information of sun-exposed
      areas were available from 8 volunteers and used for comparison with artificial
      UVB doses. However no significant solar-induced Delta25(OH)D was observed when
      sun-exposed areas were limited to hands and face. Instead the earliest period
      (week 17-19) with significant Delta25(OH)D, occurring after a mean of 2 days of
      sun-exposing more than hands and face, was used to estimate an approximate UVR
      dose required to increase 25(OH)D. This estimate resulted in a dose of 4.1 solar
      SEDs required to increase 25(OH)D by 1 nmol l(-1). The artificial dose of 6 SEDs
      of only hands and face significantly increased 25(OH)D and resulted in a dose of
      0.52 SEDs required to increase 25(OH)D significantly by 1 nmol l(-1). Artificial
      UVB was thus at least 8 times more efficient in increasing 25(OH)D than solar UVR
      at a UV-exposed area consisting of approximately hands and face. Solar UVR
      exposure of larger areas may lead to enhanced efficacy but was not relevant for
      this comparison. Significant solar-induced Delta25(OH)D was present earliest at
      April 8, maximal by early August and decreased by late August.

PMID- 22851264
TI  - [Retrospect and gratitude for 3 successful years].

PMID- 22851265
TI  - Letter to the Editor: Hofvind S, Skaane P. Stage distribution of breast cancer
      diagnosed before and after implementation of population-based mammographic
      screening. Fortschr Rontgenstr 2012; 184: 437-442.

PMID- 22851267
TI  - Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine
      responsive breast cancer: the Breast International Group 1-98 trial.

PMID- 22851268
TI  - Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine
      responsive breast cancer: the Breast International Group 1-98 trial and Re:
      CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast
      cancer patients.

PMID- 22851270
TI  - Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine
      responsive breast cancer: the Breast International Group 1-98 trial.

PMID- 22851269
TI  - Use of geriatric assessment for older adults in the oncology setting: a
      systematic review.
AB  - BACKGROUND: Geriatric assessment is a multidisciplinary diagnostic process that
      evaluates the older adult's medical, psychological, social, and functional
      capacity. No systematic review of the use of geriatric assessment in oncology has
      been conducted. The goals of this systematic review were: 1) to provide an
      overview of all geriatric assessment instruments used in the oncology setting; 2)
      to examine the feasibility and psychometric properties of those instruments; and
      3) to systematically evaluate the effectiveness of geriatric assessment in
      predicting or modifying outcomes (including the impact on treatment decision
      making, toxicity of treatment, and mortality). METHODS: We searched Medline,
      Embase, Psychinfo, Cinahl, and the Cochrane Library for articles published in
      English, French, Dutch, or German between January 1, 1996, and November 16, 2010,
      reporting on cross-sectional, longitudinal, interventional, or observational
      studies that assessed the feasibility or effectiveness of geriatric assessment
      instruments. The quality of articles was evaluated using relevant quality
      assessment frameworks. RESULTS: We identified 83 articles that reported on 73
      studies. The quality of most studies was poor to moderate. Eleven studies
      examined psychometric properties or diagnostic accuracy of the geriatric
      assessment instruments used. The assessment generally took 10-45 min. Geriatric
      assessment was most often completed to describe a patient's health and functional
      status. Specific domains of geriatric assessment were associated with treatment
      toxicity in 6 of 9 studies and with mortality in 8 of 16 studies. Of the four
      studies that examined the impact of geriatric assessment on the cancer treatment
      decision, two found that geriatric assessment impacted 40%-50% of treatment
      decisions. CONCLUSION: Geriatric assessment in the oncology setting is feasible,
      and some domains are associated with adverse outcomes. However, there is limited
      evidence that geriatric assessment impacted treatment decision making. Further
      research examining the effectiveness of geriatric assessment on treatment
      decisions and outcomes is needed.

PMID- 22851271
TI  - High-cost imaging in elderly patients with stage IV cancer.
AB  - BACKGROUND: Medicare expenditures for high-cost diagnostic imaging have risen
      faster than those for total cancer care and have been targeted for potential cost
      reduction. We sought to determine recent and long-term patterns in high-cost
      diagnostic imaging use among elderly (aged >=65 years) patients with stage IV
      cancer. METHODS: We identified claims within the Surveillance, Epidemiology, and
      End Results (SEER)-Medicare database with computed tomography, magnetic resonance
      imaging, positron emission tomography, and nuclear medicine scans between January
      1994 and December 2009 for patients diagnosed with stage IV breast, colorectal,
      lung, or prostate cancer between January 1995 and December 2006 (N = 100,594
      patients). The proportion of these patients imaged and rate of imaging per
      patient per-month of survival were calculated for each phase of care in patients
      diagnosed between January 2002 and December 2006 (N = 55,253 patients). Logistic
      regression was used to estimate trends in imaging use in stage IV patients
      diagnosed between January 1995 and December 2006, which were compared with trends
      in imaging use in early-stage (stages I and II) patients with the same tumor
      types during the same period (N = 192,429 patients). RESULTS: Among the stage IV
      patients diagnosed between January 2002 and December 2006, 95.9% underwent a high
      cost diagnostic imaging procedure, with a mean number of 9.79 (SD = 9.77) scans
      per patient and 1.38 (SD = 1.24) scans per-patient per-month of survival. After
      the diagnostic phase, 75.3% were scanned again; 34.3% of patients were scanned in
      the last month of life. Between January 1995 and December 2006, the proportion of
      stage IV cancer patients imaged increased (relative increase = 4.6%, 95%
      confidence interval [CI] = 3.7% to 5.6%), and the proportion of early-stage
      cancer patients imaged decreased (relative decrease = -2.5%, 95% CI = -3.2% to 
      1.9%). CONCLUSIONS: Diagnostic imaging is used frequently in patients with stage
      IV disease, and its use increased more rapidly over the decade of study than that
      in patients with early-stage disease.

PMID- 22851272
TI  - High-cost imaging in elderly patients with stage IV cancer: challenges for
      research, policy, and practice.

PMID- 22851273
TI  - Early detection tools for pancreatic cancer.

PMID- 22851274
TI  - Curbing U.S. health care costs: lessons from Europe?

PMID- 22851275
TI  - Online networks present challenges, opportunities for oncology.

PMID- 22851277
TI  - Dietary supplementation with N-acetyl cysteine, alpha-tocopherol and alpha-lipoic
      acid reduces the extent of oxidative stress and proinflammatory state in aged rat
      brain.
AB  - The present study has attempted to understand how oxidative stress contributes to
      the development of proinflammatory state in the brain during aging. Three groups
      of rats have been used in this study: young (4-6 months, Group I), aged (22-24
      months, Group II) and aged with dietary antioxidant supplementation (Group III).
      The antioxidants were given daily from 18 months onwards in the form of a
      combination of N-acetyl cysteine (50 mg/100 g body weight), alpha-lipoic acid (3
      mg/100 g body weight), and alpha-tocopherol (1.5 mg/100 g body weight) till the
      animals were used for the experiments between 22 and 24 months. Several
      measurements have been made to evaluate the ROS (reactive oxygen species)
      production rate, the levels of proinflammatory cytokines (IL-1beta, IL-6 and TNF
      alpha) and the activation status of NF-kappabeta (p65 subunit) in brain of the
      three groups of rats under the study. Our results reveal that brain aging is
      accompanied with a significant increase in NADPH oxidase activity and
      mitochondrial ROS production, a distinct elevation of IL-1beta, IL-6 and TNF
      alpha levels along with increased nuclear translocation of NF-kappabeta (p65
      subunit) and all these phenomena are partially but significantly prevented by the
      long-term dietary antioxidant treatment. The results imply that chronic dietary
      antioxidants by preventing oxidative stress and proinflammatory state may produce
      beneficial effects against multiple age-related deficits of the brain.

PMID- 22851278
TI  - Memristive Neuro-Fuzzy System.
AB  - In this paper, a novel neuro-fuzzy computing system is proposed where its
      learning is based on the creation of fuzzy relations by using a new implication
      method without utilizing any exact mathematical techniques. Then, a simple
      memristor crossbar-based analog circuit is designed to implement this neuro-fuzzy
      system which offers very interesting properties. In addition to high connectivity
      between neurons and being fault tolerant, all synaptic weights in our proposed
      method are always non-negative, and there is no need to adjust them precisely.
      Finally, this structure is hierarchically expandable, and it can do fuzzy
      operations in real time since it is implemented through analog circuits.
      Simulation results confirm the efficiency and applicability of our neuro-fuzzy
      computing system. They also indicate that this system can be a good candidate to
      be used for creating artificial brain. 

PMID- 22851279
TI  - Lanthanide binding and IgG affinity construct: potential applications in solution
      NMR, MRI, and luminescence microscopy.
AB  - Paramagnetic lanthanide ions when bound to proteins offer great potential for
      structural investigations that utilize solution nuclear magnetic resonance
      spectroscopy, magnetic resonance imaging, or optical microscopy. However, many
      proteins do not have native metal ion binding sites and engineering a chimeric
      protein to bind an ion while retaining affinity for a protein of interest
      represents a significant challenge. Here we report the characterization of an
      immunoglobulin G-binding protein redesigned to include a lanthanide binding motif
      in place of a loop between two helices (Z-L2LBT). It was shown to bind Tb3+ with
      130 nM affinity. Ions such as Dy3+, Yb3+, and Ce3+ produce paramagnetic effects
      on NMR spectra and the utility of these effects is illustrated by their use in
      determining a structural model of the metal-complexed Z-L2LBT protein and a
      preliminary characterization of the dynamic distribution of IgG Fc glycan
      positions. Furthermore, this designed protein is demonstrated to be a novel IgG
      binding reagent for magnetic resonance imaging (Z-L2LBT:Gd3+ complex) and
      luminescence microscopy (Z-L2LBT: Tb3+ complex).

PMID- 22851281
TI  - Otolaryngology workforce planning: why we cannot wait for perfect data.

PMID- 22851280
TI  - Growth hormone and insulin-like growth factor-I alter hippocampal excitatory
      synaptic transmission in young and old rats.
AB  - In rats, as in humans, normal aging is characterized by a decline in hippocampal
      dependent learning and memory, as well as in glutamatergic function. Both growth
      hormone (GH) and insulin-like growth factor-I (IGF-I) levels have been reported
      to decrease with age, and treatment with either GH or IGF-I can ameliorate age
      related cognitive decline. Interestingly, acute GH and IGF-I treatments enhance
      glutamatergic synaptic transmission in the rat hippocampus of juvenile animals.
      However, whether this enhancement also occurs in old rats, when cognitive
      impairment is ameliorated by GH and IGF-I (des-IGF-I), remains to be determined.
      To address this issue, we used an in vitro CA1 hippocampal slice preparation and
      extracellular recording techniques to study the effects of acute application of
      GH and IGF-I on compound field excitatory postsynaptic potentials (fEPSPs), as
      well as AMPA- and NMDA-dependent fEPSPs, in young adult (10 months) and old (28
      months) rats. The results indicated that both GH and IGF-I increased compound-,
      AMPA-, and NMDA-dependent fEPSPs to a similar extent in slices from both age
      groups and that this augmentation was likely mediated via a postsynaptic
      mechanism. Initial characterization of the signaling cascades underlying these
      effects revealed that the GH-induced enhancement was not mediated by the JAK2
      signaling element in either young adult or old rats but that the IGF-I-induced
      enhancement involved a PI3K-mediated mechanism in old, but not young adults. The
      present findings are consistent with a role for a GH- or IGF-I-induced
      enhancement of glutamatergic transmission in mitigating age-related cognitive
      impairment in old rats. 

PMID- 22851284
TI  - Degradation in the fatigue resistance of dentin by bur and abrasive air-jet
      preparations.
AB  - The objective of this investigation was to distinguish whether the instruments
      commonly used for cutting dentin cause degradation in strength or fatigue
      behavior. Beams of coronal dentin were obtained from unrestored 3(rd) molars and
      subjected to either quasi-static or cyclic flexural loading to failure. The
      surfaces of selected beams were treated with a conventional straight-sided bur or
      with an abrasive air jet laden with glass particles. Under monotonic loading,
      there was no difference in the strength or Weibull parameters obtained for the
      control or treated beams. However, the fatigue strength of dentin receiving bur
      and air-jet treatments was significantly lower (p <= 0.0001) than that of the
      control. The bur treatment resulted in the largest overall degree of degradation,
      with nearly 40% reduction in the endurance limit and even more substantial
      decrease in the fatigue life. The methods currently used for cavity preparations
      substantially degrade the durability of dentin.

PMID- 22851285
TI  - Tilted implants in the immediate loading rehabilitation of the maxilla: a
      systematic review.
AB  - Tilted implants have been proposed as an alternative to traditional protocols in
      the rehabilitation of edentulous maxillae. The aim of this meta-analysis was to
      evaluate the outcomes of upright and tilted implants supporting full-arch fixed
      dentures for the immediate rehabilitation of edentulous maxillae, after at least
      1 year of function. An electronic search of databases and a hand search of
      relevant journals in oral implantology were performed according to PRISMA
      guidelines through August, 2011. The literature search yielded 1,069 articles.
      Eleven articles were available for analysis. A total of 1,623 implants (778
      tilted, 845 upright) were inserted into the maxillae of 324 patients. Seventeen
      tilted (2.19%) and 16 upright implants (1.89%) failed during the first year. No
      significant difference in failure rate was found between tilted and upright
      implants (p value = 0.52). Marginal bone level results were obtained from 6
      studies. A non-significant mean difference between tilted and upright implants
      was found with regard to bone loss. Tilted implants demonstrated a favorable
      short-term prognosis in full-arch immediate loading rehabilitations of the
      maxillae. Randomized long-term trials are needed to better elucidate long-term
      success of tilted vs. upright-positioned implants.

PMID- 22851286
TI  - Influence of Moyamoya disease on psychopathological abnormality in young males in
      Korea: analysis of multiphasic personal inventory test.
AB  - We analyzed the results of a multiphasic personal inventory test to confirm
      whether Moyamoya disease (MMD) affects the psychopathology in a group of young
      male Koreans. The authors manually reviewed the results of the Korean military
      multiphasic personal inventory (KMPI) for the examination of conscripts in Korea
      from July 2006 to May 2010. The normal volunteers group (N = 200) was composed of
      those males who do not have any brain disease or brain trauma. The MMD group (N =
      37) was composed of those with MMD. There were more abnormal results in the MMD
      group (32.4 %) than in the normal volunteers group (13.0 %, p < 0.001). Results
      of the Neurosis Set showed that the anxiety scale, the depression scale and the
      somatization scale were more increased in the MMD group than that in the normal
      volunteer group (p = 0.014, 0.002 and 0.006, respectively). Results of the Social
      Relation Set showed that the aggregation scale was more increased in the MMD
      group than that in the normal volunteers group (p = 0.017). Young males with MMD
      may have more tendencies to have abnormal results of a multiphasic personal
      inventory test as compared to that of normal volunteers, suggesting that MMD may
      cause psychopathology in young Korean males.

PMID- 22851287
TI  - Anti-NMDAR encephalitis preceded by dura mater lesions.

PMID- 22851288
TI  - An unexpected promiscuous activity of 4-oxalocrotonate tautomerase: the cis-trans
      isomerisation of nitrostyrene.
AB  - Serendipitous switch: While exploring cis-nitrostyrene as a potential
      electrophile in Michael-type addition reactions catalysed by the enzyme 4
      oxalocrotonate tautomerase (4-OT), it was unexpectedly found that 4-OT catalyses
      the isomerisation of cis-nitrostyrene to trans-nitrostyrene (k(cat) /K(m) =
      1.9*10(3)  M(-1)  s(-1) ).

PMID- 22851289
TI  - Serum zinc and prostate cancer risk in a nested case-control study: The
      multiethnic cohort.
AB  - BACKGROUND: Experimental studies have provided evidence that zinc has a
      protective effect against development and progression of prostate cancer.
      However, epidemiological studies have reported inconsistent findings. We
      evaluated the association between prediagnostic serum zinc and prostate cancer
      risk in a cohort of multiethnic population. METHODS: This case-control study is
      nested within the Multiethnic Cohort of African Americans, Native Hawaiians,
      Japanese Americans, Latinos, and whites in Hawaii and California. The analysis
      included 392 prostate cancer cases and 783 controls matched on age,
      race/ethnicity, date/time of blood draw and fasting status. Conditional logistic
      regression was used to estimate odds ratios (OR) and 95% confidence intervals
      (CI). RESULTS: The mean serum zinc concentrations did not significantly differ
      between cases (94.9 ug/dl) and controls (93.9 ug/dl). No association was found
      between serum zinc levels and prostate cancer either overall or by tumor
      stage/grade. In ethnic-specific analyses, positive associations were found in
      Japanese Americans (OR for the highest vs. the lowest tertile = 2.59, 95% CI:
      1.09-6.17) and Latinos (OR = 2.74, 95% CI: 1.05-7.10), whereas no association was
      observed in African Americans and whites. CONCLUSIONS: We found no evidence to
      support an inverse relationship between serum zinc and prostate cancer risk, and,
      to the contrary, found a suggestion in the ethnic-specific results of a possible
      increase in risk; however, blood concentrations of zinc may not adequately
      reflect the levels in prostate tissue. Further study with a larger sample size,
      and if possible, with assessment of zinc tissue levels, is warranted to confirm
      these findings.

PMID- 22851291
TI  - The effects of gonadal steroid manipulation on the expression of Kiss1 mRNA in
      rat arcuate nucleus during postnatal development.
AB  - Kisspeptins, encoded by Kiss1 gene, play pivotal roles in the regulation of
      reproduction. Recently, several studies reported a sex difference in Kiss1
      expression in the arcuate nucleus (ARC) during the neonatal period. In this
      study, we investigated the effect of gonadal steroid manipulation on the sex
      difference in Kiss1 expression in ARC of rats. At neonatal and prepubertal
      stages, females had a greater number of Kiss1 neurons than the males. Gonadectomy
      at those stages resulted in significant increases in the Kiss1 neuron number and
      the sex differences disappeared. We also confirmed the expression of estrogen
      receptor alpha in kisspeptin neurons in neonates. Altogether, our results
      indicate that ARC Kiss1 expression is negatively regulated by gonadal steroids
      from early postnatal stages, and that the sex difference in ARC Kiss1 expression
      is attributed to the difference in circulating gonadal steroid levels. We also
      found that neonatal estrogenization inhibits Kiss1 expression and impairs
      negative feedback system.

PMID- 22851293
TI  - [Amendment to the pharmacy operations regulation 2012. New regulations in the
      field of dermatological formulations].

PMID- 22851292
TI  - Myocardial T2 mapping with respiratory navigator and automatic nonrigid motion
      correction.
AB  - Quantitative T2 mapping was recently shown to be superior to T2-weighted imaging
      in detecting T2 changes across myocardium. Pixel-wise T2 mapping is sensitive to
      misregistration between the images used to generate the parameter map. In this
      study, utility of two motion-compensation strategies-(i) navigator gating with
      prospective slice correction and (ii) nonrigid registration-was investigated for
      myocardial T2 mapping in short axis and horizontal long axis views. Navigator
      gating provides respiratory motion compensation, whereas registration corrects
      for residual cardiac and respiratory motion between images; thus, the two
      strategies provided complementary functions. When these were combined,
      respiratory-motion-induced T2 variability, as measured by both standard deviation
      and interquartile range, was comparable to that in breath-hold T2 maps. In normal
      subjects, this combined motion-compensation strategy increased the percentage of
      myocardium with T2 measured to be within normal range from 60.1% to 92.2% in
      short axis and 62.3% to 92.7% in horizontal long axis. The new motion-compensated
      T2 mapping technique, which combines navigator gating, prospective slice
      correction, and nonrigid registration to provide through-plane and in-plane
      motion correction, enables a method for fully automatic and robust free-breathing
      T2 mapping.

PMID- 22851294
TI  - [Phlebology].

PMID- 22851295
TI  - [Extensive fibromata pendulantia. Hydrosurgery as a therapy option using the
      Versajet technique].
AB  - Fibromata pendulantia often appear as small filiform skin tags with a narrow
      pedicle in the neck, axilla and groin areas. Hitherto, extensive fibromata
      pendulantia were resected either surgically (curette, scissors, scalpel) or by
      laser. The present case study of an adipose patient with disseminated fibromata
      pendulantia in the axillary region in the setting of pseudoacanthosis nigricans
      introduces the Versajet hydrosurgery technique as an alternative method. It is
      able to remove tissue and rinse the wound simultaneously by means of a high
      pressure water jet.

PMID- 22851296
TI  - [Mild form of the middle interhemispheric variant of holoprosencephaly].

PMID- 22851297
TI  - [Individual management permits contrast media enhanced CT examination without
      premedication ].

PMID- 22851298
TI  - [As time goes by--is it worth intensifying patient care during the waiting period
      for radiological examinations?].
AB  - PURPOSE: Service characteristics in hospital care in general have a high
      influence on patients' contentment. One of the key features of good service is
      waiting time. The aim of this study was to analyze the influence of ambience and
      individual care while waiting for a radiological examination on patient
      satisfaction. MATERIALS AND METHODS: The study was conducted prospectively and
      included and total of 100 patients at a tertiary care center. All patients
      waiting for contrast-enhanced computed tomography (CT) and were randomly divided
      into two groups. 50 patients waited under regular circumstances, i.e. the normal
      waiting ara of our radiological department, whilst the remaining 50 patients
      spent their waiting time in a separate small waiting area with intensified care
      and service. Both subjective and objective waiting time and the patients'
      contentment were raised with a standardized questionnaire. Quality criteria
      mentioned by the patients were then ranked according to their importance.
      RESULTS: Of all included patients 76 % were ambulant with an average age of 60
      years (range 22 - 83 years) and 69 % female. These characteristics were identical
      in both groups. With a mean waiting time of 90 minutes (Group intensified care
      100 minutes, group regular care 81 minutes) most patients evaluated the overall
      service during waiting time as "good" to "ideal", only 2 % as of "low quality".
      No significant differences between the two study arms concerning the patient
      satisfaction could be detected. Patients with intensified care estimated their
      delay time significantly shorter by an average of 24 minutes (p < 0.02). For 40 %
      a detailed consent discussion was the main quality criterion, while a short
      waiting time only for 24 %. CONCLUSION: An optimized, i.e. intensified care
      during the waiting time for a radiological examination results in a significant
      reduction of the subjective waiting time, but does not lead to a significantly
      higher patient contentment. The subjective judgement of examination quality seems
      to influence the acceptance of prolonged latency to a high degree.

PMID- 22851299
TI  - [Bronchial fibrovascular polyp in an 18-year-old patient].

PMID- 22851300
TI  - [Consensus Meeting of Course Directors in Breast Imaging, 7 May 2011, in
      Frankfurt am Main--topic: MRI of the breast].
AB  - PURPOSE: The general gap in the BIRADS lexicon between lesion description and
      categorization leads to very different recommendations in clinical breast
      radiology. This is particularly true for breast MRI. The third consensus meeting
      of course directors in breast imaging aimed at an increase in standardization of
      breast MRI. MATERIALS AND METHODS: Between 166 and 344 participants in the
      audience (A) and 9 and 13 expert panel participants (P) took part in an
      electronic wireless voting system. The audience consisted of 98% radiologists and
      2% gynecologists (A: n=295; P: n=12: radiologists 92%/gynecologists 8%). Of all
      participants, 62% had more than 10 years of experience in breast imaging and only
      9% had less than 3 years of experience (P: 100%>10 years of experience). The day
      before 44, clinically relevant, though unresolved questions were formulated by
      the expert panel. For the evaluation a distinction was made between answers with
      a great majority (>75%), simple majority (50-<75%) and no majority (<50%) as well
      as answers from the expert panel and answers from the audience. RESULTS: Of 44
      questions, all but two were answered with simple or great majority. CONCLUSION:
      Technique, reporting and clinical use are becoming more and more accurately
      defined in MRI of the breast and MR-guided interventions. The third consensus
      meeting of this kind gained numerous answers and thus enables recommendations for
      didactic as well as clinical routine work.

PMID- 22851301
TI  - [Pitfall: contrast appendix after previous oral contrast medium administration -
      erroneous interpretation as postoperative foreign body].

PMID- 22851302
TI  - The evolution of policy issues in stem cell research: an international survey.
AB  - Stem cell research remains a tremendously promising yet controversial field of
      study. It continues to attract considerable public interest and generate
      discussion and debate. However, while the high profile of this field has endured,
      the tone and nature of the discourse that drives this profile appears to be
      changing. In order to get a better sense of how these potential shifts are
      perceived by individuals directly embedded in the field, we conducted an
      international internet survey of members of the stem cell research community. Our
      participants included individuals publishing on both scientific and ethical,
      legal and social issues topics. We explored the degree to which participants
      perceived that key policy issues were becoming more or less contentious over
      time. We queried views regarding the effect of regulatory frameworks on emerging
      stem cell research technologies and the extent to which participants experience
      pressure related to clinical translation. We also explored participants'
      relationships with industry, experience with patents and perceptions regarding
      the emphasis placed on the potential economic benefits of stem cell research. Our
      results suggest that while traditional debates such as those surrounding the
      moral status of the embryo remain, other issues more closely associated with
      clinical translation and commercialization are perceived as becoming increasingly
      contentious. This survey provides useful insight into the perspectives of a
      sample of active researchers working in countries around the world as well as an
      opportunity to reflect on the likely direction of future stem cell policy
      debates.

PMID- 22851304
TI  - Evaluation of the willingness for cadaveric donation in Greece: a population
      based study.
AB  - Despite the importance of body donation for medical education and the advancement
      of medical science, cadaveric donation remains suboptimal worldwide. The purpose
      of this study was to evaluate the willingness of body donation in Greece and
      determine the characteristics of donors. This cross-sectional questionnaire
      survey was conducted from January to June 2011. A specially designed
      questionnaire was distributed to 1,700 individuals who were randomly selected
      from five major Greek cities. It was found that higher educational levels (P =
      0.002), annual family income below 30,000 Euros (P = 0.001), guaranteed
      employment status (P = 0.02), and the presence of comorbid conditions (P = 0.004)
      seemed to affect potential donors' willingness for cadaveric donation. Those with
      strong religious beliefs were found to be unwilling to donate their bodies to
      medical science. Interestingly, the majority of participants who believed that
      hospitalized patients are deceived or are used for harmful experiments were
      willing to become whole body donors (P = 0.043). In Greece, the rate of body
      donation to medical science remains low, and most Greek citizens are not willing
      to become body donors. Efforts to encourage discussions about whole body donation
      should be implemented in order to improve current low levels of donation.

PMID- 22851303
TI  - Differential modulation by delta9-tetrahydrocannabinol (?9)-THC) of CD40 ligand
      (CD40L) expression in activated mouse splenic CD4+ T cells.
AB  - The anti-inflammatory activity of cannabinoids has been widely demonstrated in
      experimental animal models and in humans. CD40-CD40-ligand (L) interactions are
      among the most crucial initiators of inflammation. This study investigated the
      effects of ?(9)-THC on CD40L expression in mouse splenic T cells after activation
      with various stimuli. Time course studies demonstrated that peak surface
      expression of CD40L by CD4(+) T cells after anti-CD3/CD28 or phorbol ester plus
      calcium ionophore (PMA/Io) occurred 8 h post activation. Peak CD40L mRNA levels
      were observed at 2 h post PMA/Io treatment and at 4 h post anti-CD3/CD28
      treatment. Pretreatment with ?(9)-THC significantly impaired the upregulation of
      CD40L induced by anti-CD3/CD28 at both the protein and mRNA level. By contrast,
      ?(9)-THC did not affect PMA/Io-induced surface CD40L expression on CD4(+) T
      cells. Additionally, ?(9)-THC also attenuated anti-CD3/CD28-induced CD40L
      expression on CD4(+) T cells derived from CB1(-/-)/CB2(-/-) mice. We investigated
      whether the mechanism by which ?(9)-THC suppressed CD40L expression involved
      putative cannabinoid activation of the glucocorticoid receptor (GR). Although
      activation of GR resulted in suppression of CD40L induction by anti-CD3/CD28, no
      interaction between ?(9)-THC and GR was observed by a glucocorticoid response
      element (GRE) luciferase reporter assay in HEK293T cells. Collectively, these
      results suggest that ?(9)-THC targets proximal T cell receptor-associated
      signaling in a cannabinoid receptor- and glucocorticoid receptor-independent
      manner. These findings identify suppression of CD40L expression as a novel part
      of the mechanism by which ?(9)-THC exerts anti-inflammatory activity.

PMID- 22851305
TI  - Pd-catalysed direct arylation polymerisation for synthesis of low-bandgap
      conjugated polymers and photovoltaic performance.
AB  - Low-bandgap conjugated copolymers based on a donor-acceptor structure have been
      synthesised via palladium-complex catalysed direct arylation polymerisation.
      Initially, we report the optimisation of the synthesis of
      poly(cyclopentadithiophene-alt-benzothiadiazole) (PCPDTBT) formed between
      cyclopentadithiophene and dibromobenzothiadiazole units. The polymerisation
      condition has been optimised, which affords high-molecular-weight polymers of up
      to M(n)  = 70 k using N-methylpyrrolidone as a solvent. The polymers are used to
      fabricate organic photovoltaic devices and the best performing PCPDTBT device
      exhibits a moderate improvement over devices fabricated using the related polymer
      via Suzuki coupling. Similar polymerisation conditions have also been applied for
      other monomer units.

PMID- 22851306
TI  - Environmental cadmium and lead exposures and hearing loss in U.S. adults: the
      National Health and Nutrition Examination Survey, 1999 to 2004.
AB  - BACKGROUND: Although cadmium and lead are known risk factors for hearing loss in
      animal models, few epidemiologic studies have been conducted on their
      associations with hearing ability in the general population. OBJECTIVES: We
      investigated the associations between blood cadmium and lead exposure and hearing
      loss in the U.S. general population while controlling for noise and other major
      risk factors contributing to hearing loss. METHODS: We analyzed data from 3,698
      U.S. adults 20-69 years of age who had been randomly assigned to the National
      Health and Nutrition Examination Survey (NHANES) 1999-2004 Audiometry Examination
      Component. Pure-tone averages (PTA) of hearing thresholds at frequencies of 0.5,
      1, 2, and 4 kHz were computed, and hearing loss was defined as a PTA > 25 dB in
      either ear. RESULTS: The weighted geometric means of blood cadmium and lead were
      0.40 [95% confidence interval (CI): 0.39. 0.42] ug/L and 1.54 (95% CI: 1.49,
      1.60) ug/dL, respectively. After adjusting for sociodemographic and clinical risk
      factors and exposure to occupational and nonoccupational noise, the highest (vs.
      lowest) quintiles of cadmium and lead were associated with 13.8% (95% CI: 4.6%,
      23.8%) and 18.6% (95% CI: 7.4%, 31.1%) increases in PTA, respectively (p-trends <
      0.05). CONCLUSIONS: Our results suggest that low-level exposure to cadmium and
      lead found in the general U.S. population may be important risk factors for
      hearing loss. The findings support efforts to reduce environmental cadmium and
      lead exposures.

PMID- 22851307
TI  - Single-step reconstitution of apo-hemoproteins at the disruption stage of
      Escherichia coli cells.
AB  - Hemoproteins on their metal: We report a novel strategy for the reconstitution of
      hemoproteins with non-natural metal complexes; simple addition of manganese and
      ruthenium porphyrin to E. coli cells immediately prior to homogenization yields
      the reconstituted proteins. We believe that this simple approach could become a
      standard reconstitution method for hemoproteins.

PMID- 22851308
TI  - Anatomicohistological characteristics of the tubular genital organs of the female
      woolly monkey (Lagothrix poeppigii).
AB  - Functional morphology of the reproductive organs is a key component for the
      better understanding of reproductive patterns as well to maximize reproductive
      efficiency and to develop assisted breeding techniques adapted to wildlife. This
      study examined anatomical and histological characteristics of genital organs of
      60 Poeppig's woolly monkey females in the wild in different reproductive stages,
      collected by rural hunters in the northeastern Peruvian Amazon. The endometrium,
      the endometrial glands, and the myometrium showed a significant increase in size
      related to the follicular growth. In nonpregnant females in the follicular phase,
      the endometrium, the endometrial glands, and the myometrium showed a significant
      increase related to the follicular growth. Nonpregnant females in the luteal
      phase had a thicker endometrium, a greater proliferation of endometrial glands,
      and a thicker myometrium, compared to females in the follicular phase.
      Nonpregnant females with small antral follicles presented high amounts of
      collagen beneath the endometrial epithelium, a sign of endometrial regeneration
      after menstruation that could be useful for the diagnosis of the reproductive
      phase in this species. A larger proportion of secreting cervical glands was
      observed in pregnant females compared to other females. The cervical mucous
      secretion occupied the lumen of the endocervical canal, assuring that no material
      could enter the uterus during gestation. The Poeppig's woolly monkey showed
      different vaginal epithelium features in accordance with the reproductive state
      of the female, suggesting that vaginal cytology could be a successful methodology
      with which to characterize the estrous cycle of wild primates. The present
      reproductive evaluation of Poeppig's woolly monkey provides important information
      that could improve the methodologies for the diagnosis of the reproductive phase
      of females, the assisted reproductive techniques in non-human primates, and could
      also give us opportunity for comparative studies and an insight into the
      evolution of animal reproductive biology, including humans.

PMID- 22851309
TI  - Incidence of snakebites in Kaltungo, Gombe State and the efficacy of a new highly
      purified monovalent antivenom in treating snakebite patients from January 2009 to
      December 2010.
AB  - Between 2009 and 2010 there were increasing incidences of snakebites in Kaltungo,
      Gombe State, Nigeria. Most of the cases presented were treated with the
      clinically approved drug of choice for snakebite, the Echitab(r) antisnake venom
      (ASV) at the Kaltungo Treatment Centre which was manufactured by MicroPharm Ltd,
      UK and produced in collaboration with the Liverpool School of Hygiene and
      Tropical Medicine. A total of 5,367 snakebite victims were treated for the two
      years under review with 82 deaths recorded. This gives a Case Fatality Rate (CFR)
      of 1.52% compared to CFR of 35-45% before treatment with this ASV. It was also
      noted that only one dose of this ASV is needed to effectively clear the venom in
      a victim while other ASVs needed up to six doses or more to clear the venom. This
      result obtained shows that this antivenom compares favourably with other
      antivenoms designed for use in Africa with respect to neutralization of the
      toxins present in the venom of Echis ocellatus. Caprylic acid fractionation of
      horse hyperimmune plasma is a simple, convenient and cheap protocol for the
      manufacture of high quality whole IgG antivenoms. It constitutes a potentially
      valuable technology for the alleviation of the critical shortage of antivenom in
      Africa.

PMID- 22851310
TI  - Stigmatic fluid aids self-pollination in Roscoea debilis (Zingiberaceae): a new
      delayed selfing mechanism.
AB  - BACKGROUND AND AIMS: Delayed selfing is the predominant mode of autonomous self
      pollination in flowering plants. However, few delayed selfing mechanisms have
      been documented. This research aims to explore a new delayed selfing mechanism
      induced by stigmatic fluid in Roscoea debilis, a small perennial ginger. METHODS:
      Floral biology and flower visitors were surveyed. The capacity of autonomous
      selfing was evaluated by pollinator exclusion. The timing of autonomous selfing
      was estimated by emasculation at different flowering stages. The number of seeds
      produced from insect-pollination was assessed by emasculation and exposure to
      pollinators in the natural population. The breeding system was also tested by
      pollination manipulations. KEY RESULTS: Autonomous self-pollination occurred
      after flowers wilted. The stigmatic fluid formed a globule on the stigma on the
      third day of flowering. The enlarged globule seeped into the nearby pollen grains
      on the fourth flowering day, thus inducing pollen germination. Pollen tubes then
      elongated and penetrated the stigma. Hand-selfed flowers produced as many seeds
      as hand-crossed flowers. There was no significant difference in seed production
      between pollinator-excluded flowers and hand-selfed flowers. When emasculated
      flowers were exposed to pollinators, they produced significantly fewer seeds than
      intact flowers. Visits by effective pollinators were rare. CONCLUSIONS: This
      study describes a new form of delayed autonomous self-pollination. As the
      predominant mechanism of sexual reproduction in R. debilis, delayed self
      pollination ensures reproduction when pollinators are scarce.

PMID- 22851311
TI  - Rain pollination provides reproductive assurance in a deceptive orchid.
AB  - BACKGROUND AND AIMS: Abiotic pollination by wind or water is well established in
      flowering plants. In some species pollination by rain splashes, a condition known
      as ombrophily, has been proposed as a floral strategy. However, evidence for this
      type of abiotic pollination has remained controversial and many reported cases
      have subsequently been shown to be false. This study investigates ombrophily in
      the deceptive orchid Acampe rigida to determine the mechanism by which this
      species is able to maintain high fecundity, despite flowering during the rainy
      season in south-west China when pollinators are scarce. METHODS: The floral
      mechanisms promoting rain pollination in A. rigida were observed and described in
      detail. Controlled pollination experiments and observations of floral visitors
      were conducted. A field experiment using rain shelters at 14 sites in Guangxi,
      south-west China, evaluated the contribution of rain pollination to fruit-set.
      KEY RESULTS: During rainfall, raindrops physically flicked away the anther cap
      exposing the pollinarium. Raindrops then caused pollinia to be ejected upwards
      with the strap-like stipe pulling them back and causing them to fall into the
      stigmatic cavity, resulting in self-pollination. Neither flower nor pollen
      function were damaged by water. Although A. rigida is self-compatible, it is
      incapable of autonomous self-pollination without the assistance of rain splashes.
      The results of the rain-sheltering experiment indicated that rain pollination
      contributed substantially to increasing fruit-set, although there was variation
      among sites in the intensity of this effect. CONCLUSIONS: A. rigida flowers
      during the rainy season, when pollinators are scarce, and ombrophily functions to
      provide reproductive assurance without compromising opportunities for
      outcrossing.

PMID- 22851312
TI  - A 64-channel 3T array coil for accelerated brain MRI.
AB  - A 64-channel brain array coil was developed and compared to a 32-channel array
      constructed with the same coil former geometry to precisely isolate the benefit
      of the 2-fold increase in array coil elements. The constructed coils were
      developed for a standard clinical 3T MRI scanner and used a contoured head-shaped
      curved former around the occipital pole and tapered in at the neck to both
      improve sensitivity and patient comfort. Additionally, the design is a compact,
      split-former design intended for robust daily use. Signal-to-noise ratio and
      noise amplification (G-factor) for parallel imaging were quantitatively evaluated
      in human imaging and compared to a size and shape-matched 32-channel array coil.
      For unaccelerated imaging, the 64-channel array provided similar signal-to-noise
      ratio in the brain center to the 32-channel array and 1.3-fold more signal-to
      noise ratio in the brain cortex. Reduced noise amplification during highly
      parallel imaging of the 64-channel array provided the ability to accelerate at
      approximately one unit higher at a given noise amplification compared to the
      sized-matched 32-channel array. For example, with a 4-fold acceleration rate, the
      central brain and cortical signal-to-noise ratio of the 64-channel array was 1.2-
      and 1.4-fold higher, respectively, compared to the 32-channel array. The
      characteristics of the coil are demonstrated in accelerated brain imaging.

PMID- 22851313
TI  - Holistic wellness assessment for young adults: psychometric analysis.
AB  - PURPOSE: The purpose of this study was to develop the Holistic Wellness
      Assessment (HWA) that incorporates conventional dimensions of wellness with a new
      dimension of wellness influencing young adults: financial wellness that is
      psychometrically sound and developmentally appropriate. DESIGN OF THE STUDY: The
      study design to establish the initial psychometrics of the HWA was the single
      group design. The cross-sectional nature of this design allowed for the
      postclassification of the participants into different demographic groups
      facilitating comparisons of the instrument's derived subscales. METHOD: From
      5,075 university students, 2,090 participants completed an online 285-item HWA
      and 2,086 respondents provided demographic information. RESULTS: Exploratory
      factor analysis of the HWA revealed eight dimensions: Self-Regard, Self-Awareness
      and Responsibility, Sustainability, Relational, Risk Prevention, Spirituality,
      Physical Health, and Health Care Maintenance. FINDINGS: Four of the eight factors
      were consistent with existing models of wellness. Three new dimensions of
      wellness- Self-Regard, Self-Awareness and Responsibility, and Sustainability
      emerged from the comprehensive item set that included financial wellness and will
      set the stage for the development and expansion of wellness models and theories.
      CONCLUSION: Initial psychometric analysis suggests that this instrument may prove
      useful in the young adult population for measuring wellness awareness curriculum
      and behavior change outcomes.

PMID- 22851314
TI  - Is there any difference between blood and crystalloid cardioplegia for myocardial
      protection during cardiac surgery? A meta-analysis of 5576 patients from 36
      randomized trials.
AB  - OBJECTIVE: To compare the efficacy of blood versus crystalloid cardioplegia for
      myocardial protection in patients undergoing cardiac surgery. METHODS: MEDLINE,
      EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of
      relevant articles were searched for clinical studies that reported in-hospital
      outcomes after blood or crystalloid cardioplegia for myocardial protection during
      cardiac surgery procedures from 1966 to 2011. The principal summary measures were
      risk ratio (RR) for blood compared to crystalloid cardioplegia with 95%
      Confidence Interval (CI) and P values (considered statistically significant when
      <0.05). The RRs were combined across studies using the DerSimonian-Laird random
      effects model and fixed effects model using the Mantel-Haenszel model - both
      models were weighted. The meta-analysis was completed using the software
      Comprehensive Meta-Analysis version 2 (Biostat Inc., Englewood, New Jersey).
      RESULTS: Thirty-six studies (randomized trials) were identified and included a
      total of 5576 patients (2834 for blood and 2742 for crystalloid). There was no
      significant difference between the blood and crystalloid groups in the risk for
      death (risk ratio [RR] 0.951, 95% CI 0.598 to 1.514, P=0.828, for both effect
      models) or myocardial infarction (RR 0.795, 95% CI 0.547 to 1.118, P=0.164, for
      both effect models) or low cardiac output syndrome (RR 0.765, 95% CI 0.580 to
      1.142, P=0.094, for the fixed effect model; RR 0.690, 95% CI 0.480 to 1.042,
      P=0.072, for the random effect model). It was observed that there was no
      publication bias or heterogeneity of effects about any outcome. CONCLUSION: We
      found evidence that argues against any superiority in terms of hard outcomes
      between blood or crystalloid cardioplegia for myocardial protection during
      cardiac surgery.

PMID- 22851315
TI  - HIV-1 Gag co-opts a cellular complex containing DDX6, a helicase that facilitates
      capsid assembly.
AB  - To produce progeny virus, human immunodeficiency virus type I (HIV-1) Gag
      assembles into capsids that package the viral genome and bud from the infected
      cell. During assembly of immature capsids, Gag traffics through a pathway of
      assembly intermediates (AIs) that contain the cellular adenosine triphosphatase
      ABCE1 (ATP-binding cassette protein E1). In this paper, we showed by
      coimmunoprecipitation and immunoelectron microscopy (IEM) that these Gag
      containing AIs also contain endogenous processing body (PB)-related proteins,
      including AGO2 and the ribonucleic acid (RNA) helicase DDX6. Moreover, we found a
      similar complex containing ABCE1 and PB proteins in uninfected cells.
      Additionally, knockdown and rescue studies demonstrated that the RNA helicase
      DDX6 acts enzymatically to facilitate capsid assembly independent of RNA
      packaging. Using IEM, we localized the defect in DDX6-depleted cells to Gag
      multimerization at the plasma membrane. We also confirmed that DDX6 depletion
      reduces production of infectious HIV-1 from primary human T cells. Thus, we
      propose that assembling HIV-1 co-opts a preexisting host complex containing
      cellular facilitators such as DDX6, which the virus uses to catalyze capsid
      assembly.

PMID- 22851316
TI  - Motor-driven motility of fungal nuclear pores organizes chromosomes and fosters
      nucleocytoplasmic transport.
AB  - Exchange between the nucleus and the cytoplasm is controlled by nuclear pore
      complexes (NPCs). In animals, NPCs are anchored by the nuclear lamina, which
      ensures their even distribution and proper organization of chromosomes. Fungi do
      not possess a lamina and how they arrange their chromosomes and NPCs is unknown.
      Here, we show that motor-driven motility of NPCs organizes the fungal nucleus. In
      Ustilago maydis, Aspergillus nidulans, and Saccharomyces cerevisiae fluorescently
      labeled NPCs showed ATP-dependent movements at ~1.0 um/s. In S. cerevisiae and U.
      maydis, NPC motility prevented NPCs from clustering. In budding yeast, NPC
      motility required F-actin, whereas in U. maydis, microtubules, kinesin-1, and
      dynein drove pore movements. In the latter, pore clustering resulted in chromatin
      organization defects and led to a significant reduction in both import and export
      of GFP reporter proteins. This suggests that fungi constantly rearrange their
      NPCs and corresponding chromosomes to ensure efficient nuclear transport and
      thereby overcome the need for a structural lamina.

PMID- 22851317
TI  - Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular
      junction synaptic membrane.
AB  - Agrin is the major factor mediating the neuronal regulation of postsynaptic
      structures at the vertebrate neuromuscular junction, but the details of how it
      orchestrates this unique three-dimensional structure remain unknown. Here, we
      show that agrin induces the formation of the dense network of microtubules in the
      subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor
      insertion into the postsynaptic membrane. Agrin acted in part by locally
      activating phosphatidylinositol 3-kinase and inactivating GSK3beta, which led to
      the local capturing of dynamic microtubules at agrin-induced acetylcholine
      receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end
      tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2,
      microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic
      AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei
      with their selective gene expression programs were all reduced. Thus, the cascade
      linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane
      is essential for the maintenance of a normal neuromuscular phenotype.

PMID- 22851318
TI  - The tumor suppressor Apc controls planar cell polarities central to gut
      homeostasis.
AB  - The stem cells (SCs) at the bottom of intestinal crypts tightly contact niche
      supporting cells and fuel the extraordinary tissue renewal of intestinal
      epithelia. Their fate is regulated stochastically by populational asymmetry, yet
      whether asymmetrical fate as a mode of SC division is relevant and whether the SC
      niche contains committed progenitors of the specialized cell types are under
      debate. We demonstrate spindle alignments and planar cell polarities, which form
      a novel functional unit that, in SCs, can yield daughter cell anisotropic
      movement away from niche-supporting cells. We propose that this contributes to SC
      homeostasis. Importantly, we demonstrate that some SC divisions are asymmetric
      with respect to cell fate and provide data suggesting that, in some SCs, mNumb
      displays asymmetric segregation. Some of these processes were altered in
      apparently normal crypts and microadenomas of mice carrying germline Apc
      mutations, shedding new light on the first stages of progression toward
      colorectal cancer.

PMID- 22851319
TI  - The transition from meiotic to mitotic spindle assembly is gradual during early
      mammalian development.
AB  - The transition from meiosis to mitosis, classically defined by fertilization, is
      a fundamental process in development. However, its mechanism remains largely
      unexplored. In this paper, we report a surprising gradual transition from meiosis
      to mitosis over the first eight divisions of the mouse embryo. The first
      cleavages still largely share the mechanism of spindle formation with meiosis,
      during which the spindle is self-assembled from randomly distributed microtubule
      organizing centers (MTOCs) without centrioles, because of the concerted activity
      of dynein and kinesin-5. During preimplantation development, the number of
      cellular MTOCs progressively decreased, the spindle pole gradually became more
      focused, and spindle length progressively scaled down with cell size. The typical
      mitotic spindle with centrin-, odf2-, kinesin-12-, and CP110-positive centrosomes
      was established only in the blastocyst. Overall, the transition from meiosis to
      mitosis progresses gradually throughout the preimplantation stage in the mouse
      embryo, thus providing a unique system to study the mechanism of centrosome
      biogenesis in vivo.

PMID- 22851320
TI  - Conformational changes in tubulin in GMPCPP and GDP-taxol microtubules observed
      by cryoelectron microscopy.
AB  - Microtubules are dynamic polymers that stochastically switch between growing and
      shrinking phases. Microtubule dynamics are regulated by guanosine triphosphate
      (GTP) hydrolysis by beta-tubulin, but the mechanism of this regulation remains
      elusive because high-resolution microtubule structures have only been revealed
      for the guanosine diphosphate (GDP) state. In this paper, we solved the
      cryoelectron microscopy (cryo-EM) structure of microtubule stabilized with a GTP
      analogue, guanylyl 5'-alpha,beta-methylenediphosphonate (GMPCPP), at 8.8-A
      resolution by developing a novel cryo-EM image reconstruction algorithm. In
      contrast to the crystal structures of GTP-bound tubulin relatives such as gamma
      tubulin and bacterial tubulins, significant changes were detected between GMPCPP
      and GDP-taxol microtubules at the contacts between tubulins both along the
      protofilament and between neighboring protofilaments, contributing to the
      stability of the microtubule. These findings are consistent with the structural
      plasticity or lattice model and suggest the structural basis not only for the
      regulatory mechanism of microtubule dynamics but also for the recognition of the
      nucleotide state of the microtubule by several microtubule-binding proteins, such
      as EB1 or kinesin.

PMID- 22851321
TI  - Imaging of the postoperative ankle and foot.

PMID- 22851323
TI  - Imaging findings in arthrofibrosis of the ankle and foot.
AB  - Arthrofibrosis is defined as joint pain and stiffness that does not allow
      functional range of motion and is due to adhesions or contracture of the joint.
      Arthrofibrosis is characterized by an abnormal proliferation of fibrous tissue
      that may be focal or diffuse and intra-articular or extra-articular. Trauma and
      surgery are the most common etiological factors. In the ankle and foot
      symptomatic arthrofibrosis is not uncommonly seen in the talocrural joint,
      posterior subtalar joint, and the metatarsophalangeal joints. Imaging can assist
      with diagnosis and planning treatment, most commonly using MRI and occasionally
      ultrasound. Typical imaging findings consist of capsular and pericapsular
      thickening and scarring, best demonstrated on proton-density MR images but also
      demonstrable on ultrasound.

PMID- 22851322
TI  - MR imaging of postoperative talar dome lesions.
AB  - The number of surgical interventions of osteochondral lesions in the talar dome
      is steadily increasing. The surgical treatment with microfracturing or autologous
      chondrocyte transplantation has shown good clinical outcome at the midterm follow
      up. With the development of advanced MR methods that are relatively specific for
      ultrastructural components of articular cartilage, compositional or biochemical
      MR has become possible in addition to the standard morphological evaluation of
      repair tissue. These quantitative MR techniques allow a monitoring of repair
      tissue on a molecular level. Using these techniques, the maturation of repair
      tissue, in particular the glycosaminoglycan content responsible for the
      biomechanical properties and the organization and content of collagen fibers, can
      be quantified and compared with normal hyaline cartilage. In addition, the
      diffusion properties of the repair tissue can also be analyzed by specific MR
      sequences.

PMID- 22851324
TI  - Imaging of postoperative avascular necrosis of the ankle and foot.
AB  - Avascular necrosis (AVN) of the ankle and foot is an uncommon and often
      unexpected postoperative complication in patients with persistent pain and
      disability postprocedure. Artifacts from metallic implants may obscure
      characteristic imaging signs of AVN, and radiography and computer tomography are
      the mainstay imaging modalities of the postoperative ankle and foot. MRI and
      nuclear medicine imaging play an important complementary role in problem solving
      and excluding differential diagnostic considerations including infection,
      nonunion, occult fracture, and secondary osteoarthritis.This review article
      evaluates different imaging modalities and discusses characteristic sites of AVN
      of the ankle and foot in the postoperative setting including the distal tibia,
      talus, navicular, and first and lesser metatarsals. Radiologists play a key role
      in the initial diagnosis of postoperative AVN and the surveillance of temporal
      evolution and complications including articular collapse and fragmentation, thus
      influencing orthopedic management.

PMID- 22851325
TI  - Imaging in total ankle replacement.
AB  - Total ankle replacement is becoming a more popular option in the treatment of end
      stage ankle arthritis. Appropriate imaging plays an important role in surgical
      planning, considering the overall foot alignment for optimal outcomes after
      surgery. Preoperative imaging includes weightbearing views of the foot and ankle,
      as well as an adjunct computed tomography scan. Imaging the painful ankle
      postsurgery often involves multiple modalities to define the underlying pathology
      and determine the appropriate management. Suggested imaging sequences are
      discussed.

PMID- 22851326
TI  - Acquired flat foot deformity: postoperative imaging.
AB  - Flat foot (pes planus) is a progressive and disabling pathology that is treated
      initially with conservative measures and often followed by a variety of
      surgeries. This article briefly reviews the pathology in acquired flat foot
      deformity, the classification of posterior tibial tendon dysfunction, discusses
      surgical techniques for the management of adult flat foot deformity, and reviews
      potential complications and their relevant imaging appearances.

PMID- 22851327
TI  - Postsurgical imaging of the peroneal tendons.
AB  - Peroneal tendon problems are most often related to two pathologies: dislocation
      or subluxation at the superior peroneal retinaculum and longitudinal split tears
      of the tendons themselves. The interpretation of postsurgical imaging is enhanced
      by understanding the surgical procedures performed to treat these. Imaging of the
      peroneal tendons is best done with combined anatomical and fluid-sensitive
      sequences, and it is especially improved by images done in a para-axial plane to
      accommodate the sharp curve in the tendons at the lateral malleolus. Use of a
      reduced field of view enhances spatial resolution.

PMID- 22851328
TI  - Postoperative infection in the foot and ankle.
AB  - Our discussion highlights the commonly performed surgical procedures in the foot
      and ankle and reviews the various imaging modalities available for the detection
      of infection with graphic examples to better enable radiologists to approach the
      radiological evaluation of postoperative infection in the foot and ankle.
      Discrimination between infectious and noninfectious inflammation remains a
      diagnostic challenge usually needing a combination of clinical assessment,
      laboratory investigations, and imaging studies to increase diagnostic accuracy.

PMID- 22851329
TI  - Neurological complications of foot and ankle surgery.
AB  - Postoperative neurological complications following foot and ankle surgery are
      common. This article reviews the structural architecture of peripheral nerves and
      innervation patterns around the foot and ankle; describes the pathophysiology of
      surgery-related nerve injury; and illustrates the postoperative neurological
      complications using specific case examples.

PMID- 22851330
TI  - Reduction of AP180 and CALM produces defects in synaptic vesicle size and
      density.
AB  - Clathrin assembly proteins AP180 and CALM regulate the assembly of clathrin
      coated vesicles (CCVs), which mediate diverse intracellular trafficking
      processes, including synaptic vesicle (SV) recycling at the synapse. Although
      studies using several invertebrate model systems have indicated a role for AP180
      in SV recycling, less is known about AP180's or CALM's function in the synapse of
      mammalian neurons. In this study, we examined synapses of rat hippocampal neurons
      in which the level of AP180 or CALM had been reduced by RNA interference (RNAi).
      Using light microscopy, we visualized synaptic puncta in these AP180- or CALM
      reduced neurons by co-expressing Synaptophysin::EGFP (Syp::EGFP). We found that
      neurons with reduced AP180 or reduced CALM had smaller Syp::EGFP-illuminated
      puncta. Using electron microscopy, we further examined the ultrastructure of the
      AP180- or CALM-reduced presynaptic terminals. We found that SVs became variably
      enlarged in both the AP180-reduced and CALM-reduced presynaptic terminals. Lower
      AP180 and CALM also reduced the density of SVs and the size of SV clusters. Our
      findings demonstrate that in the presynaptic terminals of hippocampal neurons,
      AP180 and CALM have a similar role in regulating synaptic vesicles. This
      overlapping activity may be necessary for high-precision and high-efficacy SV
      formation during endocytosis.

PMID- 22851331
TI  - Ultrasound-guided thrombin-gelatin injection is effective for the treatment of
      iatrogenic femoral artery pseudoaneurysms: initial results.
AB  - OBJECTIVES: To describe the technique of ultrasound (US)-guided percutaneous
      thrombin-gelatin injection for the treatment of femoral artery pseudoaneurysms
      (FAPs). BACKGROUND: FAPs are a possible complication from percutaneous
      angiographic procedures. US-guided thrombin injection is currently the
      preferential therapeutic option, limited by a low risk of potentially
      catastrophic femoral thrombosis; transluminal injection of collagen is another
      effective and safe option, although a more invasive one; surgical repair is
      associated with significant comorbidity. We hypothesized that US-guided combined
      thrombin and gelatin injection (UG-TGI) would also be effective while minimizing
      the risk of limb thrombosis. METHODS: Review of the results, complications and
      length of hospital admission after the injection into the FAP sac of combined
      human-origin thrombin and bovine-origin gelatin matrix (FloSeal((r)), Baxter),
      under direct US-guidance. RESULTS: We treated 13 patients (mean age 64 +/- 9.46
      years, 38% male), who developed a FAP following a percutaneous procedure:
      isolated coronariography in five (38%); angioplasty in four (31%); other cardiac
      procedures in four (31%). Immediate success was obtained in all (100%) patients,
      assessed by US; no allergic reactions, local infection, or embolic events
      occurred on 30-day follow-up. Median (interquartile range) admission time after
      the UG-TGI was 2 days (1.25-2.0); median time of total admission was 8 days (6.5
      16.25). CONCLUSIONS: In this small study, UG-TGI for the treatment of FAP was
      feasible and had short-term effectiveness, without a learning curve effect.
      Despite the need for further experience, a trial comparing different therapies
      for FAP should include this procedure.

PMID- 22851332
TI  - The expression and actions of androgen receptor in upper urinary tract urothelial
      carcinoma (UUTUC) tissues and the primary cultured cells.
AB  - Sex hormone receptors, androgen receptor (AR) and estrogen receptors (ERs)
      including both ERalpha and ERbeta, mediate the actions of sex hormones. In this
      study, we aimed to evaluate sex hormone receptors expression in upper urinary
      tract urothelial carcinomas (UUTUCs) of ureter and renal pelvis with different
      tumor stages and grades as well as their possible roles in tumor progression.
      Immunohistochemistry was used to assay the expression of AR and ERs in the
      primary UUTUCs. XTT viability test was applied to evaluate cell responses for
      anticancer drug treatment. Wound healing assay was performed to determine cell
      migration abilities. AR and ERbeta immunoreactivities were observed in both
      UUTUCs, but ERalpha was not detected in either UUTUCs. In UUTUC of ureter
      specimens, higher AR expression was found in superficial or lower grade tumors.
      In contrast, little difference of ERbeta expression was found in superficial
      versus muscle-invasive tumor stages or low grades versus high grades in UUTUCs of
      ureter specimens. Furthermore in the primary cultured cells from UUTUC specimens,
      the addition of functional AR reduced cell chemosensitivity, but increased cell
      migration. These results provide the first data showing the expression patterns
      of sex hormone receptors in both renal pelvis and ureter UUTUCs. From results, we
      concluded that there is a positive correlation for higher AR expression found in
      superficial or low-grade UUTUCs of ureter and identified the functional roles of
      AR in UUTUC progression.

PMID- 22851334
TI  - Hyperpolarized singlet NMR on a small animal imaging system.
AB  - Nuclear spin hyperpolarization makes a significant advance toward overcoming the
      sensitivity limitations of in vivo magnetic resonance imaging, particularly in
      the case of low-gamma nuclei. The sensitivity may be improved further by storing
      the hyperpolarization in slowly relaxing singlet populations of spin-1/2 pairs.
      Here, we report hyperpolarized (13) C spin order transferred into and retrieved
      from singlet spin order using a small animal magnetic resonance imaging scanner.
      For spins in sites with very similar chemical shifts, singlet spin order is
      sustained in high magnetic field without requiring strong radiofrequency
      irradiation. The demonstration of robust singlet-to-magnetization conversion, and
      vice versa, on a small animal scanner, is promising for future in vivo and
      clinical deployments.

PMID- 22851333
TI  - Coronary microvascular function in patients with Cushing's syndrome.
AB  - The aim of the study was to evaluate patients with Cushing's syndrome the
      coronary flow reserve (CFR), an index of coronary microvascular function. Fifteen
      newly diagnosed patients with Cushing's syndrome (1 male/14 females; mean age 45
      +/- 11 years), were selected for having no clinical evidence of ischemic heart
      disease. Twelve patients had pituitary-dependent Cushing's disease and three had
      an adrenal adenoma. Fifteen subjects matched for age, sex, and major
      cardiovascular risk factors were used as controls. Coronary flow velocity in the
      left anterior descending coronary artery was investigated by transthoracic
      Doppler echocardiography at rest and during adenosine infusion. CFR was obtained
      as the ratio hyperemic/resting diastolic flow velocity. A reduced coronary
      reserve (hyperemic/resting ratio <= 2.5) was found in 5/15 Cushing patients and
      4/15 controls. In all patients with abnormal CFR, epicardial coronary stenosis
      was excluded by multi-slice computed tomographic coronary angiography. CFR was
      inversely related to urinary cortisol in patients with endogenous
      hypercortisolism (Spearman's rho = -0.57, P = 0.03), while no correlation was
      found in controls. Coronary microvascular function, as assessed by CFR, is
      pathologically reduced in a considerable number of patients with Cushing's
      syndrome without clinical symptoms of ischemic heart disease and in the absence
      of epicardial coronary artery lesions, as well as in controls matched for
      cardiovascular risk factors. The presence of comorbidities can explain this early
      coronary abnormality in both patients and controls. Whether urinary cortisol may
      be a predictor of coronary microvascular function in the setting of patients with
      Cushing's syndrome, needs further investigation.

PMID- 22851335
TI  - Reward and non-reward learning of flower colours in the butterfly Byasa alcinous
      (Lepidoptera: Papilionidae).
AB  - Learning plays an important role in food acquisition for a wide range of insects.
      To increase their foraging efficiency, flower-visiting insects may learn to
      associate floral cues with the presence (so-called reward learning) or the
      absence (so-called non-reward learning) of a reward. Reward learning whilst
      foraging for flowers has been demonstrated in many insect taxa, whilst non-reward
      learning in flower-visiting insects has been demonstrated only in honeybees,
      bumblebees and hawkmoths. This study examined both reward and non-reward learning
      abilities in the butterfly Byasa alcinous whilst foraging among artificial
      flowers of different colours. This butterfly showed both types of learning,
      although butterflies of both sexes learned faster via reward learning. In
      addition, females learned via reward learning faster than males. To the best of
      our knowledge, these are the first empirical data on the learning speed of both
      reward and non-reward learning in insects. We discuss the adaptive significance
      of a lower learning speed for non-reward learning when foraging on flowers.

PMID- 22851336
TI  - Population genetics of the Washington National Primate Research Center's (WaNPRC)
      captive pigtailed macaque (Macaca nemestrina) population.
AB  - Pigtailed macaques (Macaca nemestrina) provide an important model for biomedical
      research on human disease and for studying the evolution of primate behavior. The
      genetic structure of captive populations of pigtailed macaques is not as well
      described as that of captive rhesus (M. mulatta) or cynomolgus (M. fascicularis)
      macaques. The Washington National Primate Research Center houses the largest
      captive colony of pigtailed macaques located in several different housing
      facilities. Based on genotypes of 18 microsatellite (short tandem repeat [STR])
      loci, these pigtailed macaques are more genetically diverse than captive rhesus
      macaques and exhibit relatively low levels of inbreeding. Colony genetic
      management facilitates the maintenance of genetic variability without
      compromising production goals of a breeding facility. The periodic introduction
      of new founders from specific sources to separate housing facilities at different
      times influenced the colony's genetic structure over time and space markedly but
      did not alter its genetic diversity significantly. Changes in genetic structure
      over time were predominantly due to the inclusion of animals from the Yerkes
      National Primate Research Center in the original colony and after 2005.
      Strategies to equalize founder representation in the colony have maximized the
      representation of the founders' genomes in the extant population. Were exchange
      of animals among the facilities increased, further differentiation could be
      avoided. The use of highly differentiated animals may confound interpretations of
      phenotypic differences due to the inflation of the genetic contribution to
      phenotypic variance of heritable traits.

PMID- 22851338
TI  - Diaphragmatic hernia after hepatic resection: case series at a single Western
      institution.
AB  - BACKGROUND: Diaphragmatic hernia (DH) after hepatic resection (HR) is a rare and
      not well-described complication. We report our experience with DH following a
      high volume of HRs in a tertiary center. METHODS: Records of patients undergoing
      major HR for liver tumors between April 1992 and November 2011 were reviewed. The
      definitive diagnosis of DH was made based on radiologic studies. Primary repair
      was used for defects <10 cm in size. Transthoracic repair was used in patients
      with recurrent or complex hernias. Univariate analysis was performed to determine
      risk factors associated with posthepatectomy DH. RESULTS: DH developed in 10 out
      of 993 patients (1%) at a median time interval of 15 months after HR. DH was not
      associated with old age (m = 48.5 years), gender (male = 50%), or high body mass
      index (m = 24.5). However, mean tumor size was large (m = 9.2 cm). The majority
      of patients presented with symptoms (80 %), small (60%) and right-sided (80%)
      hernias, and underwent elective repair via an abdominal approach (70%). Large
      defects (>10 cm; 30%) were successfully repaired with prosthetic mesh. Increased
      incidence of DH was associated with diaphragmatic resection at the time of HR
      (5.4 vs. 0.7%, p = 0.001). At a median follow-up of 36 months (range, 10-167
      months) after hernia repair, recurrence occurred in one patient. CONCLUSION:
      Diaphragmatic resection at the time of HR and large tumor size may put patients
      at risk of developing posthepatectomy DH. Early detection and prompt treatment is
      associated with low recurrence and offers the advantage of primary repair.

PMID- 22851340
TI  - Using neuroimaging and neuromodulation to study changes in brain functioning with
      therapy.
AB  - This article reviews the concepts underlying functional neuroimaging and its use
      to study brain function change as a result of recovery and neurorehabilitation
      for speech, voice, and swallowing. The role of neurovascular coupling for
      quantifying brain function change in response to behavioral demands is explained.
      The types of changes in brain function that are measured and how they should be
      interpreted are addressed for the study of brain function abnormalities in
      developmental and acquired speech, voice, and swallowing disorders. One challenge
      is to separate changes in brain function due to recovery from those that are
      secondary to the development of compensatory skills during therapy. The
      advantages of functional magnetic resonance imaging and functional near-infrared
      spectroscopy are compared. The use of transcranial magnetic stimulation for the
      study of brain function is reviewed. In addition, more recent methods for the
      modulation of brain function using transcranial magnetic and electrical
      stimulation over the cortex are examined. These technologies can be used by
      clinical investigators to gain better understanding of normal brain function and
      for learning how abnormalities in brain function might be addressed. Both are
      likely to lead to new therapeutic approaches to neurorehabilitation of speech,
      voice, and swallowing disorders.

PMID- 22851341
TI  - Transcranial brain stimulation to treat aphasia: a clinical perspective.
AB  - Transcranial brain stimulation was first introduced and described during mid
      1900s. Since that time, the literature on brain stimulation has expanded with
      spurious advances in techniques and applications, from its use as a purely
      investigative tool used to better understand brain mechanisms to its use as a
      clinical treatment for neurologic diseases. This article offers a brief overview
      of the development, history, and mechanisms of transcranial brain stimulation, as
      well as an in-depth discussion of transcranial magnetic stimulation and
      transcranial direct current stimulation; two methods currently being investigated
      as treatments for aphasia. Our aim is to provide speech-language pathologists
      with an overview of the current state of literature on transcranial brain
      stimulation, as initial findings show it may be a promising new tool for aphasia
      rehabilitation.

PMID- 22851337
TI  - 450K epigenome-wide scan identifies differential DNA methylation in newborns
      related to maternal smoking during pregnancy.
AB  - BACKGROUND: Epigenetic modifications, such as DNA methylation, due to in utero
      exposures may play a critical role in early programming for childhood and adult
      illness. Maternal smoking is a major risk factor for multiple adverse health
      outcomes in children, but the underlying mechanisms are unclear. OBJECTIVE: We
      investigated epigenome-wide methylation in cord blood of newborns in relation to
      maternal smoking during pregnancy. METHODS: We examined maternal plasma cotinine
      (an objective biomarker of smoking) measured during pregnancy in relation to DNA
      methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from
      the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium
      HumanMethylation450 BeadChip (450K). RESULTS: We found differential DNA
      methylation at epigenome-wide statistical significance (p-value < 1.06 * 10-7)
      for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1,
      and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth
      cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor
      signaling pathway, which mediates the detoxification of the components of tobacco
      smoke. GFI1 is involved in diverse developmental processes but has not previously
      been implicated in responses to tobacco smoke. CONCLUSIONS: We identified a set
      of genes with methylation changes present at birth in children whose mothers
      smoked during pregnancy. This is the first study of differential methylation
      across the genome in relation to maternal smoking during pregnancy using the 450K
      platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the
      adverse health outcomes associated with this important in utero exposure.

PMID- 22851342
TI  - Electrical stimulation and swallowing: how much do we know?
AB  - Consequences of dysphagia substantially reduce quality of life, increase the risk
      of medical complications and mortality, and pose a substantial cost to healthcare
      systems. As a result, it is of no wonder that the clinical and scientific
      communities are showing interest in new avenues for dysphagia rehabilitation.
      Electrical stimulation (e-stim) for the treatment of swallowing impairments is
      among the most studied swallowing interventions in the published literature, yet
      many unanswered questions about its efficacy remain. In the meantime, many speech
      language pathologists who treat dysphagia are attending educational and training
      sessions to obtain certifications to use this technique. Here, we review the
      values and limitations of the published literature on the topic of e-stim for
      swallowing to assist clinicians in decision making in their clinical practice.
      The discussion provides a review of swallowing anatomy and physiology, the
      fundamentals of e-stim, and information essential for the readers' independent
      critique of these studies--all of which are crucial for evaluating the possible
      effects of e-stim.

PMID- 22851343
TI  - AphasiaBank: a resource for clinicians.
AB  - AphasiaBank is a shared, multimedia database containing videos and transcriptions
      of ~180 aphasic individuals and 140 nonaphasic controls performing a uniform set
      of discourse tasks. The language in the videos is transcribed in Codes for the
      Human Analysis of Transcripts (CHAT) format and coded for analysis with
      Computerized Language ANalysis (CLAN) programs, which can perform a wide variety
      of language analyses. The database and the CLAN programs are freely available to
      aphasia researchers and clinicians for educational, clinical, and scholarly uses.
      This article describes the database, suggests some ways in which clinicians and
      clinician researchers might find these materials useful, and introduces a new
      language analysis program, EVAL, designed to streamline the transcription and
      coding processes, while still producing an extensive and useful language profile.

PMID- 22851344
TI  - How to use apps clinically in the treatment of aphasia.
AB  - This article is designed to provide aphasia clinicians with some general
      guidelines for selecting apps that are appropriate for individuals on their
      caseloads. Further, it provides a template, consisting of some things we have
      learned while we have instituted the use of apps at the Adler Aphasia Center in
      Maywood, NJ and at the Carondelet Aphasia Program in Tucson, AZ, in the hopes
      that clinicians who are interested in using this technology can profit from our
      experiences.

PMID- 22851345
TI  - Steps to success with technology for individuals with aphasia.
AB  - This article discusses how the Snyder Center for Aphasia Life Enhancement, an
      aphasia center in Baltimore, MD, currently uses technology in its programming to
      empower individuals with aphasia to actively participate in communications with
      families, friends, and the community. We describe the steps used to promote
      successful use of technology in everyday life. This process includes: (1)
      identifying a client's strongest modality/modalities for communication; (2)
      matching the individual's strengths with their personal goals and preferences;
      (3) developing a way to determine personal goals for technology use; and (4)
      selecting and training use of technologies that will support them in achieving
      their goals. Three brief case studies are presented to demonstrate the process by
      which programs were judged to be "best fits" for each member, and permitted them
      to reach a self-chosen goal. Finally, the steps that promoted successful learning
      and generalization to everyday life are described.

PMID- 22851346
TI  - Telerehabilitation, virtual therapists, and acquired neurologic speech and
      language disorders.
AB  - Telerehabilitation (telerehab) offers cost-effective services that potentially
      can improve access to care for those with acquired neurologic communication
      disorders. However, regulatory issues including licensure, reimbursement, and
      threats to privacy and confidentiality hinder the routine implementation of
      telerehab services into the clinical setting. Despite these barriers, rapid
      technological advances and a growing body of research regarding the use of
      telerehab applications support its use. This article reviews the evidence related
      to acquired neurologic speech and language disorders in adults, focusing on
      studies that have been published since 2000. Research studies have used telerehab
      systems to assess and treat disorders including dysarthria, apraxia of speech,
      aphasia, and mild Alzheimer disease. They show that telerehab is a valid and
      reliable vehicle for delivering speech and language services. The studies
      represent a progression of technological advances in computing, Internet, and
      mobile technologies. They range on a continuum from working synchronously (in
      real-time) with a speech-language pathologist to working asynchronously (offline)
      with a stand-in virtual therapist. One such system that uses a virtual therapist
      for the treatment of aphasia, the Web-ORLATM (Rehabilitation Institute of
      Chicago, Chicago, IL) system, is described in detail. Future directions for the
      advancement of telerehab for clinical practice are discussed.

PMID- 22851348
TI  - From the Levant to Gibraltar: a regional perspective for marine conservation in
      the Mediterranean Sea.
AB  - Marine protected areas (MPAs) are critical to the well-being of threatened
      ecosystems and thus can be highly beneficial to humans, especially to those
      residing nearby. We explore the qualities of 117 MPAs in the Mediterranean basin
      and develop a taxonomy of their characteristics. We relate the spatial
      distribution of the MPAs to the various characteristics of the taxonomy (size,
      distance from shore, protection levels, management regimes, etc.) and to areas of
      high human impact and influence levels. To do this we use information on
      biogeographic regions and information from two different human influence models;
      one model developed for the marine environment and one covering the littoral
      terrestrial environment. Our analysis provides insights to planners and managers
      working in a regional capacity and trying to build MPA networks. Generally,
      current MPAs have not been established in high impact areas despite their being
      close to shores containing intense human activity. Decision-makers wishing to
      design and establish new MPAs may seek out areas of high cumulative human impacts
      (near the marine-terrestrial interface) or avoid them depending on marine
      conservation objectives, including the desire to vary types of MPAs within a
      network. Limitations of our analysis and methodology indicate areas for further
      research.

PMID- 22851349
TI  - Linking climate trends to population dynamics in the Baltic ringed seal: impacts
      of historical and future winter temperatures.
AB  - A global trend of a warming climate may seriously affect species dependent on sea
      ice. We investigated the impact of climate on the Baltic ringed seals (Phoca
      hispida botnica), using historical and future climatological time series.
      Availability of suitable breeding ice is known to affect pup survival. We used
      detailed information on how winter temperatures affect the extent of breeding ice
      and a climatological model (RCA3) to project the expected effects on the Baltic
      ringed seal population. The population comprises of three sub-populations, and
      our simulations suggest that all of them will experience severely hampered growth
      rates during the coming 90 years. The projected 30, 730 seals at the end of the
      twenty-first century constitutes only 16 % of the historical population size, and
      thus reduced ice cover alone will severely limit their growth rate. This adds
      burden to a species already haunted by other anthropogenic impacts.

PMID- 22851350
TI  - Metabolism, compartmentation, transport and production of acetate in the cortical
      brain tissue slice.
AB  - Acetate is a two carbon intermediate in metabolism. It is an accepted marker of
      astrocytic metabolism, and a substrate for production of metabolites such as
      glutamine, glutamate and GABA. However, anomalies exist in the current
      explanations of compartmentation and metabolism of acetate. Here, we investigated
      these anomalies by examining transport, production and metabolism of acetate.
      Acetate is a good substrate for the neuronal monocarboxylate transporter MCT2
      (K(M) = 2.58 +/- 0.8) and the glial MCT1 but a poor substrate for the glial MCT4.
      Acetate is accumulated by brain cortical tissue slices to concentrations in
      excess of those in the media, suggesting active transport, possibly via the
      sodium dependent SMCT. [2-(13)C]Acetate is produced from [3-(13)C]pyruvate, [3
      (13)C]lactate and [1-(13)C]glucose with the rate of production related to acetyl
      CoA levels, which is likely generated in a ubiquitous cytosolic compartment via
      acetyl-CoA hydrolase. Citrate breakdown occurs in response to demand for acetyl
      CoA units; this citrate is not derived from acetate carbon but its fate is
      influenced by acetate levels. Finally, use of acetate is altered by levels of
      nicotinamide or NAD(+). This suggests that metabolism of acetate is controlled
      rigorously at the enzyme level, via changes in the acetylation status of acetyl
      CoA synthetase and is not regulated by restriction of uptake.

PMID- 22851351
TI  - Involvement of peripheral NMDA receptor in melittin-induced thermographic flare.
AB  - Intradermal injection of an active compound of European honeybee toxin, melittin,
      into the forearm in humans produces temporary pain and evokes sustained increase
      of local skin temperature. This increase of skin temperature is suppressed by the
      pretreatment of a voltage gated sodium channel blocker, lidocaine, suggesting
      that neurogenic inflammation is involved in the skin temperature increase after
      the melittin treatment. In this study, we tested a hypothesis that the melittin
      induced skin temperature increase is augmented by an N-methyl-D-aspartate (NMDA)
      glutamate receptor that is present on the peripheral terminals of cutaneous
      primary afferents. Skin temperature was examined after the local application of
      incremental doses of melittin by a computer-assisted-thermography in
      pentobarbital-anesthetized rats. Local subcutaneous glutamate was collected
      through a microdialysis probe and glutamate levels were measured by a high
      pressure liquid chromatography with electrochemical detection method.
      Intraplantar injection of melittin resulted in the increase of subcutaneous
      glutamate levels and the increase of local skin temperature, which was partially
      attenuated by co-injection of an NMDA receptor antagonist, MK-801. In addition,
      intraplantar injection of NMDA itself increased the local skin temperature. Our
      data suggest that melittin-induced increase of skin temperature is enhanced
      through the activation of peripheral NMDA receptors by locally released
      glutamate. We suggest that topical administration of NMDA receptor antagonists
      could be an effective treatment of neuro-inflammatory pain.

PMID- 22851352
TI  - Brain-derived neurotrophic factor levels in women with postpartum affective
      disorder and suicidality.
AB  - Our aim was to investigate serum brain-derived neurotrophic factor (BDNF) levels
      in postpartum women, according to the presence of postpartum affective disorder
      (PPAD) and suicidality. A cross-sectional study was carried out with women
      between 45 and 90 days after delivery. PPAD (depression, manic and mixed episode)
      and suicide risk were assessed using the Mini International Neuropsychiatric
      Interview. BDNF was assessed using a commercial ELISA kit. Linear regression was
      used for multivariate analyses. A hundred ninety women participated in the study,
      15.3 % had PPAD, 7.4 % showed PPAD with suicide risk. BDNF levels were lower in
      subjects with three or more Stressful Life Events (P = 0.01). The serum BDNF
      levels of women with PPAD presenting suicide risk were significantly lower than
      those of women without suicide risk (1.50 +/- 1.38 and 2.33 +/- 1.28 ng/ml, P =
      0.02). Clinicians should enquire postpartum women about their history of
      stressful life events, PPAD, and suicidality. This study shows the potential role
      of BDNF in the neurobiology of the association of PPAD and suicidality.

PMID- 22851353
TI  - Interaction of inhibition and triplets of excitatory spikes modulates the NMDA-R
      mediated synaptic plasticity in a computational model of spike timing-dependent
      plasticity.
AB  - Spike timing-dependent plasticity (STDP) experiments have shown that a synapse is
      strengthened when a presynaptic spike precedes a postsynaptic one and depressed
      vice versa. The canonical form of STDP has been shown to have an asymmetric shape
      with the peak long-term potentiation at +6 ms and the peak long-term depression
      at -5 ms. Experiments in hippocampal cultures with more complex stimuli such as
      triplets (one presynaptic spike combined with two postsynaptic spikes or one
      postsynaptic spike with two presynaptic spikes) have shown that pre-post-pre
      spike triplets result in no change in synaptic strength, whereas post-pre-post
      spike triplets lead to significant potentiation. The sign and magnitude of STDP
      have also been experimentally hypothesized to be modulated by inhibition.
      Recently, a computational study showed that the asymmetrical form of STDP in the
      CA1 pyramidal cell dendrite when two spikes interact switches to a symmetrical
      one in the presence of inhibition under certain conditions. In the present study,
      I investigate computationally how inhibition modulates STDP in the CA1 pyramidal
      neuron dendrite when it is driven by triplets. The model uses calcium as the
      postsynaptic signaling agent for STDP and is shown to be consistent with the
      experimental triplet observations in the absence of inhibition: simulated pre
      post-pre spike triplets result in no change in synaptic strength, whereas
      simulated post-pre-post spike triplets lead to significant potentiation. When
      inhibition is bounded by the onset and offset of the triplet stimulation, then
      the strength of the synapse is decreased as the strength of inhibition increases.
      When inhibition arrives either few milliseconds before or at the onset of the
      last spike in the pre-post-pre triplet stimulation, then the synapse is
      potentiated. Variability in the frequency of inhibition (50 vs. 100 Hz) produces
      no change in synaptic strength. Finally, a 5% variation in model's calcium
      parameters (calcium thresholds) proves that the model's performance is robust.

PMID- 22851355
TI  - Guidelines for the validation of qualitative multi-residue methods used to detect
      pesticides in food.
AB  - There is a current trend for many laboratories to develop and use qualitative gas
      chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass
      spectrometry (LC-MS) based multi-residue methods (MRMs) in order to greatly
      increase the number of pesticides that they can target. Before these qualitative
      MRMs can be used for the monitoring of pesticide residues in food, their fitness
      for-purpose needs to be established by initial method validation. This paper sets
      out to assess the performances of two such qualitative MRMs against a set of
      parameters and criteria that might be suitable for their effective validation. As
      expected, the ease of detection was often dependent on the particular
      pesticide/commodity combinations that were targeted, especially at the lowest
      concentrations tested (0.01 mg/kg). The two examples also clearly demonstrated
      that the percentage of pesticides detected was dependent on many factors, but
      particularly on the capabilities of the automated software/library packages and
      the parameters and threshold settings selected for operation. Another very
      important consideration was the condition of chromatographic system and detector
      at the time of analysis. If the system was relatively clean, then the detection
      rate was much higher than if it had become contaminated over time from previous
      injections of sample extracts. The parameters and criteria suggested for method
      validation of qualitative MRMs are aimed at achieving a 95% confidence level of
      pesticide detection. However, the presence of any pesticide that is 'detected'
      will need subsequent analysis for quantification and, depending on the
      qualitative method used, further evidence of identity.

PMID- 22851354
TI  - EU sampling strategies for the detection of veterinary drug residues in
      aquaculture species: are they working?
AB  - Over the past 50 years, the culture of aquatic species in controlled conditions
      to enhance production has grown in importance and now provides nearly 50% of the
      world's seafood supply. In part, this expansion has been made possible by the use
      of antibiotics, antifungals, and other veterinary medicines to control disease
      and improve welfare. Despite guidelines being available, the sampling programmes
      for drug residue surveillance of aquaculture products recommended by the CODEX
      Alimentarius Commission were withdrawn in 2008 and put under review. Directive
      96/23/EC sets out legislation to govern how sampling programmes for drug residue
      surveillance should be conducted within the EU. This directive applies both to
      produce raised within the EU and also imported products from third countries.
      This communication examines the existing EU sampling regimen for aquaculture
      products and comments on its possible application in a global context. We examine
      UK statutory sampling data that, while indicating the effectiveness of the
      directive, also suggests that the directive may lead to unnecessary sampling.
      Regarding imports, examination of the Rapid Alert System for Food and Feed
      (RASFF) database using process control charts and statistical modelling suggests
      that the sampling regimen described in the directive is effective but not
      sufficiently flexible for the range of aquaculture practices that exist.
      Limitations of the directive, datasets, and practices are further discussed.

PMID- 22851356
TI  - Analytical difficulties facing today's regulatory laboratories: issues in method
      validation.
AB  - The challenges facing analytical laboratories today are not unlike those faced in
      the past, although both the degree of complexity and the rate of change have
      increased. Challenges such as development and maintenance of expertise,
      maintenance and up-dating of equipment, and the introduction of new test methods
      have always been familiar themes for analytical laboratories, but international
      guidelines for laboratories involved in the import and export testing of food
      require management of such changes in a context which includes quality assurance,
      accreditation, and method validation considerations. Decisions as to when a
      change in a method requires re-validation of the method or on the design of a
      validation scheme for a complex multi-residue method require a well-considered
      strategy, based on a current knowledge of international guidance documents and
      regulatory requirements, as well the laboratory's quality system requirements.
      Validation demonstrates that a method is 'fit for purpose', so the requirement
      for validation should be assessed in terms of the intended use of a method and,
      in the case of change or modification of a method, whether that change or
      modification may affect a previously validated performance characteristic. In
      general, method validation involves method scope, calibration-related parameters,
      method precision, and recovery. Any method change which may affect method scope
      or any performance parameters will require re-validation. Some typical situations
      involving change in methods are discussed and a decision process proposed for
      selection of appropriate validation measures.

PMID- 22851357
TI  - Combining ISO/IEC 17025:2005 and European Commission Decision 2002/657 audit
      requirements: a practical way forward.
AB  - Laboratories involved in the analyses of veterinary drug residues are under
      increasing pressure to demonstrate that they produce meaningful and reliable
      data. Quality assurance and quality control systems are implemented in
      laboratories to provide evidence of this and these are subject to external
      assessment to ensure that they are effective. Audits to ISO/IEC 17025:2005, an
      internationally accepted standard, and subsequent accreditation provide
      laboratories and their customers with a degree of assurance that the laboratories
      are operating in control and the data they report can be relied on. However,
      national or regional authorities may place additional requirements on
      laboratories to ensure quality data are reported. For example, in the European
      Union, all official control laboratories involved in veterinary drug residue
      analyses must also meet the requirements of European Commission Decision
      2002/657/EC which sets performance criteria for analytical methods used in this
      area and these are subject to additional audits by national or regional
      authorities. All audits place considerable time and resource demands on
      laboratories and this paper discusses the burden audits place on laboratories and
      describes a UK initiative to combine these audits to the benefit of both the
      regulatory authority and the laboratory.

PMID- 22851358
TI  - Application of EU guidelines for the validation of screening methods for
      veterinary drugs.
AB  - Commission Decision (CD) 2002/657/EC describes detailed rules for method
      validation within the framework of residue monitoring programmes. The approach
      described in this CD is based on criteria. For (qualitative) screening methods,
      the most important criteria is that the CCbeta has to be below any regulatory
      limit. Especially when microbiological or immunochemical methods are involved,
      the approach described in the CD is not easily applied. For example, by those
      methods, a large number of analytes (all antibiotics) within several different
      matrices (meat, milk, fish, eggs, etc.) are detected. It is not completely clear
      whether all those analytes and all matrices have to be taken into account during
      method validation. To clarify this, a working group - from EU Reference
      Laboratories - came up with a practical approach to validate multi-analyte multi
      matrix screening methods. It describes how many analyte/matrix combinations have
      to be tested and how these combinations are selected. Furthermore it describes
      how to determine CCbeta for screening methods in relation to a large list of
      compounds and maximum residue limits (MRLs). First for each analyte/matrix
      combination the 'cut-off' level - i.e. the level at which the method separates
      blanks from contaminated samples - is established. The validation is preferably
      at the concentration of 50% of the regulatory limit. A minimum set of 20
      different samples has to be tested. From the experiences with applying these
      guidelines it was concluded that the validation approach is very 'practical';
      however, there are some remarks. One has to be careful with selecting
      'representative' analytes and matrices and it is strongly recommended to collect
      additional validation data during the routine application of the method.

PMID- 22851359
TI  - The role of pharmacokinetics in veterinary drug residues.
AB  - This review provides a summary of those pharmacokinetic properties of veterinary
      drugs relevant to marker residues, marker tissues, and residue depletion rates.
      The scientific literature in this field is very extensive and there is also a
      wealth of data available on the websites of various regulatory jurisdictions.
      Therefore, this review is limited to selected examples, cited to illustrate
      general principles. The areas considered are: (1) the relationship of dose to
      plasma concentration through the pharmacokinetic properties, area under plasma
      concentration-time curve, bioavailability, and clearance; (2) the critical
      dependence of drug pharmacokinetics and residue depletion on product formulation;
      (3) disease state and population pharmacokinetics; and (4) the requirement for
      residue depletion studies for generic products shown to be bioequivalent to
      pioneer products.

PMID- 22851360
TI  - A review of analytical strategies for the detection of 'endogenous' steroid abuse
      in food production.
AB  - Detection of the abuse of synthetic steroids in food production is nowadays
      relatively straightforward using modern techniques such as gas or liquid
      chromatography coupled to mass spectrometry (GC-MS/MS or LC-MS/MS, respectively).
      However, proving the abuse of 'endogenous' (or naturally occurring) steroids is
      more difficult. Despite these difficulties, significant progress in this area has
      recently been made and a number of methods are now available. The aim of the
      current review was to systematically review the available analytical approaches,
      which include threshold concentrations, qualitative 'marker' metabolites, intact
      steroid esters, gas chromatography-combustion-isotope ratio mass spectrometry (GC
      C-IRMS), longitudinal testing and 'omics' biomarker profiling. The
      advantages/disadvantages of these methods are considered in detail, but the
      choice of which to adopt is dictated by a number of practical, political, and
      economic factors, which vary in different parts of the world. These include the
      steroid/species combination requiring analysis, the matrix tested, whether
      samples are collected from live or slaughtered animals, available analytical
      instrumentation, sample throughput/cost, and the relevant legal/regulatory
      frameworks. Furthermore, these approaches could be combined in a range of
      different parallel and/or sequential screening/confirmatory testing streams, with
      the final choice being determined by the aforementioned considerations. Despite
      these advances, more work is required to refine the different techniques and to
      respond to the ever increasing list of compounds classified as 'endogenous'. At
      this advanced stage, however, it is now more important than ever for scientists
      and regulators from across the world to communicate and collaborate in order to
      harmonize and streamline research efforts.

PMID- 22851361
TI  - Risk assessment and risk management at the Canadian Food Inspection Agency
      (CFIA): a perspective on the monitoring of foods for chemical residues.
AB  - The Canadian Food Inspection Agency (CFIA) uses 'Ranked Risk Assessment' (RRA) to
      prioritize chemical hazards for inclusion in monitoring programmes or method
      development projects based on their relative risk. The relative risk is
      calculated for a chemical by scoring toxicity and exposure in the 'risk model
      scoring system' of the Risk Priority Compound List (RPCL). The relative ranking
      and the risk management options are maintained and updated in the RPCL. The
      ranking may be refined by the data generated by the sampling and testing
      programs. The two principal sampling and testing programmes are the National
      Chemical Residue Monitoring Program (NCRMP) and the Food Safety Action Plan
      (FSAP). The NCRMP sampling plans focus on the analysis of federally registered
      products (dairy, eggs, honey, meat and poultry, fresh and processed fruit and
      vegetable commodities, and maple syrup) for residues of veterinary drugs,
      pesticides, environmental contaminants, mycotoxins, and metals. The NCRMP is
      complemented by the Food Safety Action Plan (FSAP) targeted surveys. These
      surveys focus on emerging chemical hazards associated with specific foods or
      geographical regions for which applicable maximum residue limits (MRLs) are not
      set. The data from the NCRMP and FSAP also influence the risk management (follow
      up) options. Follow-up actions vary according to the magnitude of the health
      risk, all with the objective of preventing any repeat occurrence to minimize
      consumer exposure to a product representing a potential risk to human health.

PMID- 22851362
TI  - Metabolomics in food analysis: application to the control of forbidden
      substances.
AB  - Metabolomics is a science of interest in food analysis to describe and predict
      properties of food products and processes. It includes the development of
      analytical methods with the ultimate goal being the identification of so-called
      'quality markers', (i.e. sets of metabolites that correlate with, for example,
      quality, safety, taste, or fragrance of foodstuffs). In turn, these metabolites
      are influenced by factors as genetic differences of the raw food ingredients
      (such as animal breed or crop species differences), growth conditions (such as
      climate, irrigation strategy, or feeding) or production conditions (such as
      temperature, acidity, or pressure). In cases where the routine-based measurement
      of a food property faces some limitations such as the lack of knowledge regarding
      the target compounds to monitor, monitoring based on a limited set of crucial
      biomarkers is a good alternative, which is of great interest for food safety
      purposes regarding growth promoting practices. Such an approach may be more
      efficient than using a classic approach based on a limited set of known
      metabolites of anabolic compounds. In this context, screening strategies allowing
      detection of the physiological response resulting from anabolic compound
      administration are promising approaches to detect their misuse. The global
      metabolomics workflow implemented for such studies is presented and illustrated
      through various examples of biological matrices profiling (tissue, blood, urine)
      and for different classes of anabolic compounds (steroids, beta-agonists and
      somatotropin).

PMID- 22851363
TI  - The physiological way: monitoring RNA expression changes as new approach to
      combat illegal growth promoter application.
AB  - The use of growth-promoting agents in food-producing animals is forbidden in the
      European Union (EU). Therefore a strict control programme has been developed,
      detecting residues of all known growth-promoting agents using chromatographical
      methods in combination with mass spectrometry or immunoassays. New designed
      xenobiotic substances or hormone cocktails are difficult to identify with these
      methods and therefore the development of new sensitive test methods is important.
      A promising indirect approach is the detection of physiological effects of the
      administered growth promoters on the molecular level using 'omic' technologies.
      The analysis of the transcriptome on mRNA and miRNA level and thereby identifying
      biomarkers for the use of anabolic agents is one possible strategy for developing
      a new screening method. This paper describes the technologies available for gene
      expression profiling and summarizes the efforts made in the analysis of the
      transcriptome in order to identify potential gene expression biomarkers for the
      use of growth promoters in cattle.

PMID- 22851364
TI  - Development and validation of a streamlined method designed to detect residues of
      62 veterinary drugs in bovine kidney using ultra-high performance liquid
      chromatography--tandem mass spectrometry.
AB  - In the USA, the US Department of Agriculture's Food Safety and Inspection Service
      (FSIS) conducts the National Residue Program designed to monitor veterinary drug
      and other chemical residues in beef and other slaughtered food animals.
      Currently, FSIS uses a 7-plate bioassay in the laboratory to screen for
      antimicrobial drugs in bovine kidneys from those animals tested positive by
      inspectors in the slaughter establishments. The microbial inhibition bioassay has
      several limitations in terms of monitoring scope, sensitivity, selectivity, and
      analysis time. Ultra-high performance liquid chromatography - tandem mass
      spectrometry (UHPLC-MS/MS) has many advantages over the bioassay for this
      application, and this study was designed to develop, evaluate, and validate a
      fast UHPLC-MS/MS method for antibiotics and other high-priority veterinary drugs
      in bovine kidney. Five existing multi-class, multi-residue methods from the
      literature were tested and compared, and each performed similarly. Experiments
      with incurred samples demonstrated that a 5-min shake of 2 g homogenized kidney
      with 10 ml of 4/1 (v/v) acetonitrile/water followed by simultaneous clean-up of
      the initial extract with 0.5 g C18 and 10 ml hexane gave a fast, simple, and
      effective sample preparation method for the <10 min UHPLC-MS/MS analysis. An
      extensive 5-day validation process demonstrated that the final method could be
      used to acceptably screen for 54 of the 62 drugs tested, and 50 of those met
      qualitative MS identification criteria. Quantification was not needed in the
      application, but the method gave >= 70% recoveries and <= 25% reproducibilities
      for 30 of the drugs.

PMID- 22851365
TI  - Evaluation of a multi-class, multi-residue liquid chromatography-tandem mass
      spectrometry method for analysis of 120 veterinary drugs in bovine kidney.
AB  - Traditionally, regulatory monitoring of veterinary drug residues in food animal
      tissues involves the use of several single-class methods to cover a wide
      analytical scope. Multi-class, multi-residue methods (MMMs) of analysis tend to
      provide greater overall laboratory efficiency than the use of multiple methods,
      and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of targeted drug
      analytes usually provides exceptional performance even for complicated sample
      extracts. In this work, an LC-MS/MS method was optimized and validated in a test
      of 120 drug analytes from 11 different classes in bovine kidney. The method used
      10 ml of 4/1 acetonitrile/water for extraction of 2 g samples and cleanup with
      hexane partitioning. Quantitative and qualitative performance was assessed for
      the analytes at fortification levels of 10, 50, 100, and 200 ng/g. With the
      method, 66 drugs gave 70-120% recovery with <= 20% RSD at all levels over the
      course of 3 days. At the 200 ng/g level, 89 drugs met these same standards.
      Limits of detection were <= 10 ng/g for 109 of the analytes in the kidney matrix
      in validation experiments. Qualitatively, MS/MS identification criteria were set
      that ion ratios occur within +/- 10% (absolute value) from those of the analyte
      reference standards. At the 10 ng/g level, 57% of the drugs met the
      identification criteria, which improved to 84% at the 200 ng/g level. The method
      serves as an efficient and useful additional option among the current monitoring
      methods available.

PMID- 22851366
TI  - The challenges of developing a generic extraction procedure to analyze multi
      class veterinary drug residues in milk and honey using ultra-high pressure liquid
      chromatography quadrupole time-of-flight mass spectrometry.
AB  - This paper discusses the analytical challenges to develop a generic extraction
      procedure to analyze or screen multi-class veterinary drugs in milk and honey
      using ultra-high pressure liquid chromatography quadrupole time-of-flight mass
      spectrometry (UHPLC QqTOF MS). The veterinary drugs in this study included
      aminoglycosides, endectocides, fluoroquinolones, ionophores, beta-lactams or
      penicillins, macrolides, NSAIDs, phenicols, sulfonamides and tetracyclines.
      Veterinary drugs were extracted using a QuEChERS (quick, easy, cheap, effective,
      rugged, and safe) method, which entailed the use of acetonitrile containing 1%
      acetic acid, sodium acetate, ethylenediaminetetra acetic acid disodium (EDTA) and
      magnesium sulfate, and no clean-up was performed. Chromatographic separation was
      achieved on a reversed-phase Acquity UPLC BEH C(18) , 100 * 2.1 mm, 1.7 um column
      with 0.1% formic acid and 10 mM ammonium formate in water, and acetonitrile as
      mobile phases. Due to poor chromatographic retention, aminoglycosides were first
      dropped from the list, and because of poor extractability, beta-lactams and
      tetracyclines were also excluded from the method. The method was able to quantify
      31 or screen up to 54 drugs (unbound) in honey, and to quantify 34 or screen up
      to 59 drugs in milk. UHPLC QqTOF data were acquired in TOF MS full-scan mode that
      allowed both quantification and confirmation of veterinary drugs and
      identification of their degradation products in samples. The method could achieve
      detection limits as low as 1 ug/kg with analytical range from 1 to 100 ug/kg. The
      developed method was intended to be used for screening of as many analytes as
      possible in one single analysis, or unequivocal confirmation of positive findings
      and degradation product identification based on accurate mass measurement and
      isotopic patterns.

PMID- 22851367
TI  - Determination of hexaconazole in field samples of an oil palm plantation.
AB  - In oil palm plantations, the fungicide hexaconazole is used to control Ganoderma
      infection that threatens to destroy or compromisethe palm. The application of
      hexaconazole is usually through soil drenching, trunk injection, or a combination
      of these two methods. It is therefore important to have a method to determine the
      residual amount of hexaconazole in the field such as in samples of water, soil,
      and leaf to monitor the use and fate of the fungicide in oil palm plantations.
      This study on the behaviour of hexaconazole in oil palm agro-environment was
      carried out at the UKM-MPOB Research Station, Bangi Lama, Selangor. Three
      experimental plots in this estate with 7-year-old Dura x Pisifera (DxP) palms
      were selected for the field trial. One plot was sprayed with hexaconazole at the
      manufacturer's recommended dosage, one at double the recommended dosage, and the
      third plot was untreated control. Hexaconazole residues in the soil, leaf, and
      water were determined before and after fungicide treatment. Soil samples were
      randomly collected from three locations at different depths (0-50 cm) and soil
      collected fromthe same depth were bulked together. Soil, water, and palm leaf
      were collected at -1 (day before treatment), 0 (day of treatment), 1, 3, 7, 14,
      21, 70, 90, and 120 days after treatment. Hexaconazole was detected in soil and
      oil palm leaf, but was not detected in water from the nearby stream.

PMID- 22851368
TI  - Investigation into the experimental protocols required to determine maximum
      residue limits (MRLs) in honey.
AB  - There is current debate within the EU, and internationally, on how withdrawal
      periods and maximum residue limits (MRLs) may be set for honey production. Whilst
      comprehensive EU guidelines exist for calculating the withdrawal times of
      veterinary medicines in most food-producing species, the analytical variables to
      be studied for bees/honey are not well defined. The objective of this study was
      therefore to investigate and understand the factors, for example sampling
      variability, that is important in the development of a harmonized protocol that
      can be used to generate the robust scientific data necessary to assist risk
      assessors in proposing MRLs for honey. Ten bee colonies were treated in the
      spring with a model compound (ciprofloxacin). One hive was used to study intra
      hive variation in residue concentrations and the other nine were used in an inter
      hive study over a 41-week sampling period. All samples were analyzed using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The highest mean
      concentration from nine hives used in the inter-hive study was 4627 ug/kg eight
      days (D8) after treatment. The concentration of ciprofloxacin declined to an
      average concentration of 1756 ug/kg at D30 and 733 ug/kg at D283 (over-winter
      sample). A generalized additive model was used to fit a smooth curve for trend
      estimation. For some individual hives the concentration of ciprofloxacin
      increased slightly at the later sampling time-points. Consequently it was not
      possible to interpolate, with confidence, a finite withdrawal period for
      ciprofloxacin at theoretical MRLs between 25 and 500 ug/kg. The observed
      variation in concentration of ciprofloxacin between hives indicates that the
      validity of the EU guideline for bees/honey, which requires five samples from
      five hives to calculate a withdrawal period, may require revision.

PMID- 22851369
TI  - Monitoring of florfenicol residues in fish muscle by HPLC-UV with confirmation of
      suspect results by LC-MS/MS.
AB  - Florfenicol, a derivative of thiamphenicol in which the hydroxyl group at C-3 has
      been replaced with fluorine, is listed by the World Health Organization as an
      antibacterial agent for human medicine that is critically important in risk
      management strategies for non-human use. AOAC International has also identified
      it as an important molecule for the development of effective methods for the
      seafood sector. Following inspection missions from the European Union and United
      States of America, it was introduced in the Brazilian Residues Control Program to
      fulfill export and internal national requirements with a Maximum Residue Limit of
      800 ug/kg. A high performance liquid chromatography method with ultraviolet
      detection at a wavelength of 230 nm (lambda = 230 nm) for the detection of
      florfenicol in fish muscle was developed and validated according to the Brazilian
      Regulation 24/2009 (equivalent to European Union Decision 2002/657/EC). Fish
      samples were extracted with ethyl acetate and hexane followed by C18 solid phase
      clean-up and chromatographic separation on a reversed-phase C18 LC column with
      acetonitrile:water as mobile phase. The method results were also was compared
      with those obtained using liquid chromatography-tandem quadrupole mass
      spectrometry. The method meets the Brazilian regulatory requirements with a
      decision limit (CCalpha) of 840 ug/kg and detection capability (CCbeta) of 879
      ug/kg. This method is easy to use and has been implemented into Brazil's residue
      control program, with liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      confirmation of any suspect samples using the same method.

PMID- 22851370
TI  - Validation of a new screening, determinative, and confirmatory multi-residue
      method for nitroimidazoles and their hydroxy metabolites in turkey muscle tissue
      by liquid chromatography-tandem mass spectrometry.
AB  - A new and sensitive multi-residue method (MRM) with detection by LC-MS/MS was
      developed and validated for the screening, determination, and confirmation of
      residues of 7 nitroimidazoles and 3 of their metabolites in turkey muscle tissues
      at concentrations >= 0.05 ng/g. The compounds were extracted into a solvent with
      an alkali salt. Sample clean-up and concentration was then done by solid-phase
      extraction (SPE) and the compounds were quantified by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). The characteristic parameters including
      repeatability, selectivity, ruggedness, stability, level of quantification, and
      level of confirmation for the new method were determined. Method validation was
      achieved by independent verification of the parameters measured during method
      characterization. The seven nitroimidazoles included are metronidazole (MTZ),
      ronidazole (RNZ), dimetridazole (DMZ), tinidazole (TNZ), ornidazole (ONZ),
      ipronidazole (IPR), and carnidazole (CNZ). It was discovered during the single
      laboratory validation of the method that five of the seven nitroimidazoles (i.e.
      metronidazole, dimetridazole, tinidazole, ornidazole and ipronidazole) and the 3
      metabolites (1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (MTZ-OH), 2
      hydroxymethyl-1-methyl-5-nitroimidazole (HMMNI, the common metabolite of
      ronidazole and dimetridazole), and 1-methyl-2-(2'-hydroxyisopropyl)-5
      nitroimidazole (IPR-OH) included in this study could be detected, confirmed, and
      quantified accurately whereas RNZ and CNZ could only be detected and confirmed
      but not accurately quantified.

PMID- 22851371
TI  - Retroperitoneal fibrosis as a result of signet ring cell gastric cancer: a case
      based review.
AB  - BACKGROUND: Retroperitoneal fibrosis is a rare and obvious condition in the
      abdominopelvic cavity. Signet ring cell carcinoma of the stomach with gross
      appearance of linitis plastica is another rare association. CASE PRESENTATION: We
      present a rare case of a 49-year-old woman presenting with persistent nausea and
      vomiting for 20 days. Three months ago, she was admitted with severe flank pain
      and was referred to the urology service. She was placed with stents for
      strictures in both ureters. She underwent endoscopy for heartburn, melena,
      dyspepsia, and weight loss (7 kg/5 month), which revealed congestion of the
      mucosa of the fundus and body with fine linear erosion and decreased
      distensibility of the stomach suggesting linitis plastica. A biopsy indicated
      full-thickness infiltration by signet ring cell gastric cancer. A CT scan showed
      evidence of retroperitoneal fibrosis with large lymph nodes around the aorta.
      CONCLUSION: This paper shows that the gastric linitis plastica can present with
      many deceptive clinical presentations, raising the risk of postponed diagnosis.

PMID- 22851372
TI  - Cancer chemotherapeutic agents as human teratogens.
AB  - BACKGROUND: Cancer is the second leading cause of death among women of
      reproductive age. Although the coincidence of pregnancy and cancer is rare and
      treatment may sometimes be safely delayed, the use of chemotherapeutic agents in
      pregnancy is sometimes unavoidable or inadvertent. METHODS: We review the
      literature for the use of antineoplastic agents in single-agent and combination
      therapy from 1951 through June 2012. We also summarize the evidence relating to
      teratogenicity of disorder-specific combination chemotherapy treatments for those
      malignancies frequently encountered in women of childbearing age. Major endpoints
      were called "adverse pregnancy outcomes" (APOs), to include structural anomalies
      (congenital malformations), functional defects, blood or electrolyte
      abnormalities, stillbirths, spontaneous abortions (miscarriages), and fetal,
      neonatal, or maternal deaths. RESULTS: The registry totals 863 cases. Rates of
      APOs (and congenital malformations) after any exposure were 33% (16%), 27% (8%),
      and 25% (6%), for first, second, and third trimesters. Among the groups of cancer
      drugs, antimetabolites and alkylating agents have the highest rates of APOs.
      Mitotic inhibitors and antibiotics seem more benign. Mixed results were observed
      from single-agent exposure, often because of small numbers of exposures. As a
      whole, the alkylating agents and antimetabolites are more harmful when given as a
      single agent rather than as part of a regimen. First-trimester exposure poses a
      more permanent risk to the fetus. CONCLUSIONS: Systematic ascertainment of women
      early in pregnancy, preferably in a population base, is needed for assessment of
      true risks. Long-term follow-up is needed to rule out neurobehavioral effects.

PMID- 22851373
TI  - Reliability and validity of the acanthosis nigricans screening tool for use in
      elementary school-age children by school nurses.
AB  - The purpose of this study was to test the reliability and validity of an
      acanthosis nigricans (AN) screening tool for use in elementary school-age
      children of different ethnic groups. Cross-sectional data were collected via
      observation of 288, 5- to 12-year-old school-age children. Three nurse clinicians
      used a 0-4 grade AN screening tool to rate each child's level of AN
      independently. AN was consistently and appropriately identified in elementary
      school-age children from different ethnic groups. All clinicians were within one
      grade 98% of the time. Substantial agreement among raters was found (kappa
      statistic = .822, p <= .001), indicating similar interpretation and
      reproducibility of the AN screening tool. There was more consistent detection of
      grade four AN regardless of the children's sex, body mass index, or ethnic group.
      The AN screening tool is easy to use and reliable for use with elementary school
      age children of various ethnic groups.

PMID- 22851374
TI  - Evaluation of heterogeneous metabolic profile in an orthotopic human glioblastoma
      xenograft model using compressed sensing hyperpolarized 3D 13C magnetic resonance
      spectroscopic imaging.
AB  - High resolution compressed sensing hyperpolarized (13)C magnetic resonance
      spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for
      quantitative assessment of spatial variations in (13)C metabolic profiles and
      comparison with histopathology. A new compressed sensing sampling design with a
      factor of 3.72 acceleration was implemented to enable a factor of 4 increase in
      spatial resolution. Compressed sensing 3D (13)C magnetic resonance spectroscopic
      imaging data were acquired from a phantom and 10 tumor-bearing rats following
      injection of hyperpolarized [1-(13)C]-pyruvate using a 3T scanner. The (13)C
      metabolic profiles were compared with hematoxylin and eosin staining and carbonic
      anhydrase 9 staining. The high-resolution compressed sensing (13)C magnetic
      resonance spectroscopic imaging data enabled the differentiation of distinct
      (13)C metabolite patterns within abnormal tissues with high specificity in
      similar scan times compared to the fully sampled method. The results from
      pathology confirmed the different characteristics of (13)C metabolic profiles
      between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue.

PMID- 22851375
TI  - The role of minerals in food selection in a black howler monkey (Alouatta pigra)
      population in Belize following a major hurricane.
AB  - As plants may contain low levels of some minerals including sodium, copper, and
      phosphorous, herbivores may become deficient in these nutrients. In 2001,
      Hurricane Iris hit the Monkey River Forest in Belize causing substantial damage
      to the food supply of the black howler monkey population (Alouatta pigra) living
      there. This included an 18-month absence in fruit production and a complete loss
      of figs that are high in calcium. In this article, we describe the post-hurricane
      diet of this monkey population and compare the mineral content of food items to
      each other and to recommendations for non-human primates [NRC 2003]. We also
      investigate food selection in relation to potentially limiting minerals.
      Behavioral data from four groups of howlers (2002-2006) and samples of all
      ingested food items were collected and a sample of 99 plant from 18 food species
      was analyzed for mineral content. Unexpectedly, the post-hurricane diet contained
      more mature leaves than new leaves despite the availability of new leaves. Leaves
      contained higher amounts of minerals than reproductive parts and with the
      exception of Cecropia peltata stems, plant parts were low in sodium. Cecropia
      peltata is a pioneer species that grows following habitat disturbance thus the
      ingestion of these stems may be a potential mechanism to avoid sodium deficiency
      in this damaged forest. Calcium and zinc were found above recommended values in
      most food items; however, both positively predicted food selection, which may
      reflect a difference between their abundance and their bioavailability. However,
      as mature leaves contained more calcium than other plant parts, their high post
      hurricane consumption may also be a response to the absence of figs and the need
      to find an alternate calcium source. This study highlights how habitat
      disturbance may affect mineral abundance and the dietary choices of primates.

PMID- 22851376
TI  - Negative priming persists in the absence of response-retrieval.
AB  - The hypothesis that retrieval of the prime response is responsible for the
      negative priming (NP) effect has gained popularity in recent studies of visual
      identity NP. In the current study we report an experiment in which we aimed to
      remove the response from the prime memory trace by means of spatio-temporal
      separation. Compared to an identical experiment without this separation (Ihrke et
      al., 2011), we find that the response-retrieval-specific interaction is absent
      indicating that the separation was successful in preventing response-retrieval.
      Still, both negative and positive priming are present as main effects which show
      that processes other than response-retrieval can produce NP. In addition, based
      on recordings of the eye-movements during task processing, we localize the NP
      effect in a target-selection process while positive priming manifests in
      facilitated response-selection. Our results are in line with a multiple-route
      view of NP.

PMID- 22851377
TI  - Eye movements and practice effects in the attentional dwell time paradigm.
AB  - In the attentional dwell time paradigm by Duncan, Ward, and Shapiro (1994), two
      backward masked targets are presented at different spatial locations and
      separated by a varying time interval. Results show that report of the second
      target is severely impaired when the time interval is less than 500 ms which has
      been taken as a direct measure of attentional dwell time in human vision.
      However, we show that eye movements may have confounded the estimate of the dwell
      time and that the measure may not be robust as previously suggested. The latter
      is supported by evidence suggesting that intensive training strongly attenuates
      the dwell time because of habituation to the masks. Thus, this article points to
      eye movements and masking as two potential methodological pitfalls that should be
      considered when using the attentional dwell time paradigm to investigate the
      temporal dynamics of attention.

PMID- 22851378
TI  - Inhibition does not always cause emotional devaluation: no evidence for retrieval
      induced devaluation.
AB  - Retrieval practice for some memory items from a given category can impair
      subsequent retrieval of unpracticed items from the same category (retrieval
      induced forgetting, RIF). Inhibition of these items has been invoked as an
      explanation, and inhibition has also been proposed to cause stimulus devaluation.
      The present experiments investigated whether a similar devaluation effect can be
      observed in a RIF experiment for the unpracticed and presumably inhibited items.
      We report two experiments using the RIF paradigm, and both experiments yielded a
      RIF effect. At the same time, affective ratings of the very same items did not
      show signs of devaluation. These results run counter the idea that both RIF and
      devaluation effects are caused by a (similar) inhibitory mechanism, or at least
      they suggest differences between the mechanisms involved in external perceptual
      and internal memory selection.

PMID- 22851379
TI  - How object shape affects visual metaphor processing.
AB  - In order to interpret novel metaphoric relations, we have to construct ad hoc
      categories under which the metaphorically related concepts can be subsumed. Shape
      is considered to be one of the primary vehicles of object categorization.
      Accordingly, shape might play a prominent role in interpreting visual metaphors
      (i.e., two metaphorically related objects depicted in one visual array). This
      study explores the role of object shape in visual metaphor interpretation of 10-
      to 12-year-olds. The experiment shows that participants can produce more
      correspondences between similarly shaped objects as compared to dissimilarly
      shaped objects and that they need less thinking time to do so. These findings
      suggest that similarity in shape facilitates the process of interpreting visual
      metaphors.

PMID- 22851380
TI  - The joys of spring.
AB  - This study used Vivaldi's Four Seasons, an extraordinary example of program
      music, to explore the consequence of music exposure on cognitive event-related
      potentials (ERPs). Seventeen participants performed a three-stimulus visual odd
      ball task while ERPs were recorded. Participants were required to differentiate
      between a rare target stimulus (to elicit a memory updating component; P3b), a
      rare novel stimulus (to elicit a novelty attention component; P3a), and a
      frequent nontarget stimulus. During task performance participants listened to the
      four concertos: Spring, Summer, Autumn, and Winter in comparison to a silent
      control condition. Additionally, the three movements of each concerto have a
      fast, slow, fast structure that enabled examination of the impact of tempo. The
      data revealed that "Spring," particularly the well-recognized, vibrant, emotive,
      and uplifting first movement, had the ability to enhance mental alertness and
      brain measures of attention and memory.

PMID- 22851381
TI  - Strategic control modulates working memory-driven attentional capture.
AB  - The current study used a naming task to investigate whether strategic control
      could modulate the process of attentional capture that is driven by working
      memory. The use of a naming task to engage working memory eliminates potential
      strategic perceptual resampling, which may have played a role in several previous
      studies. After naming a prime, participants performed a selection task in which
      they judged the direction of a moving target in each trial. Prime validity, which
      is the probability that the primes are identical to the selection targets, was
      manipulated across four experiments. The results showed that reaction times to
      the motion judgment were faster in the valid condition than in the invalid
      condition when the prime validity was 50% (Experiment 1A). These results occurred
      even in the presence of a highly informative spatial cue that predicted the
      target's location (Experiment 4). A larger capturing effect was observed when the
      validity was 70% (Experiments 2 and 3). When the prime validity was lower than
      the chance level (0% in Experiment 1B; 15% in Experiments 2 and 3), a validity
      effect was not observed. Thus, the results suggest that there is a strong
      tendency for working memory to capture attention by default when there is no
      reason to avoid the influence of primes. When there is a reason to avoid the
      influence, strategic control modulates the attentional capture that is driven by
      working memory.

PMID- 22851382
TI  - Retraction of "Construing collective concerns: increasing cooperation by
      broadening construals in social dilemmas".
AB  - The following article has been retracted by the Editor and publishers of
      Psychological Science at the request of the lead author, Lawrence J. Sanna:
      Sanna, L. J., Chang, E. C., Parks, C. D., & Kennedy, L. A. (2009). Construing
      collective concerns: Increasing cooperation by broadening construals in social
      dilemmas. Psychological Science, 20, 1319-1321. doi:10.1111/j.1467
      9280.2009.02458.x In a letter to the Editor (Eric Eich), Dr. Sanna wrote:  The
      data reported in this article are invalid and should not be considered part of
      the scientific literature. The responsibility for this problem rests solely with
      the first author, Lawrence J. Sanna. Coauthors Edward C. Chang, Craig D. Parks,
      and Lindsay A. Kennedy are in no way responsible for this problem. In response,
      the Editor noted that Psychological Science follows the retraction guidelines
      developed by the Committee on Publication Ethics (COPE). Dr. Sanna was urged to
      follow these guidelines carefully in drafting a retraction notice, particularly
      with respect to stating the reasons for the retraction, to distinguish misconduct
      from honest error. To assist Dr. Sanna with this task, the Editor provided Dr.
      Sanna with a copy of the COPE guidelines
      (http://publicationethics.org/resources/guidelines) and a link to a retraction
      notice that was published in Psychological Science last year. This notice was
      considered a "model" by Retraction Watch, and Dr. Sanna was advised that, in
      keeping with this notice, he "must specify clearly the reasons for the retraction
      in such language that all of your coauthors agree to it." While awaiting Dr.
      Sanna's reply, the Editor sought to contact Dr. Sanna's three coauthors. Although
      one coauthor was aware of Dr. Sanna's request to retract the 2009 Psychological
      Science article, the other two were not. All of the coauthors have agreed to
      retraction of the article, and each has received a copy of this notice. Dr. Sanna
      replied by noting with regret that "research errors" have made it necessary for
      him to request retraction. The letter concluded with the following: "At the
      direction of legal counsel, I am unable to say anything further than that
      contained in my previous letter at this time." Because it is unclear when, if
      ever, details on these research errors will be forthcoming, the Editor owes it to
      the journal's readership to retract the article now, even though this notice does
      not reflect COPE guidelines or journal policy.

PMID- 22851388
TI  - [Prevention and nursing care of central line-associated bloodstream infections in
      critically ill patients].
AB  - Catheter-related bloodstream infections are associated with significantly
      increased morbidity, mortality, and expenditures. Such infections are a serious
      threat to patient safety in the intensive care unit. This review describes the
      latest protocols related to preventing and treating central venous catheter
      associated bloodstream infections in critically ill patients. According to 2011
      Center for Disease Control (CDC) guidelines and central line care bundles by the
      institute for healthcare improvement (IHI), prevention measures for catheter
      related bloodstream infections include the following: hand hygiene, maximal
      barrier precautions insertion, chlorhexidine skin antisepsis, optimal catheter
      site selection, proper catheter maintenance, insertion site care, and daily
      review of line necessity, with prompt removal of unnecessary lines. These are
      important and effective infection prevention measures. Guidelines and care
      bundles also recommend organizing care modules based on unit characteristics;
      integrating resources and empirical measures; education and training to promote
      comprehensive implementation; and auditing and monitoring to ensure staff
      continue to follow procedures. Effectively preventing central venous catheter
      related bloodstream infections can enhance care quality and move healthcare
      closer to achieving the goal of zero tolerance.

PMID- 22851387
TI  - Human trigeminal ganglionic explants as a model to study alphaherpesvirus
      reactivation.
AB  - Varicella zoster virus (VZV) latency is characterized by limited virus gene
      expression and the absence of virus DNA replication. Investigations of VZV
      latency and reactivation have been hindered by the lack of an in vitro model of
      virus latency. Since VZV is an exclusively human pathogen, we used naturally
      infected human trigeminal ganglia (TG) obtained at autopsy to study virus
      latency. Herein, we report optimization of medium to maintain TG integrity as
      determined by histology and immunohistochemistry. Using the optimized culture
      medium, we also found that both herpes simplex virus-1 (HSV-1) and VZV DNA
      replicated in TG explants after 5 days in culture. The increase in HSV-1 DNA was
      fourfold greater than the increase in VZV DNA. Overall, we present a model for
      alphaherpesvirus latency in human neurons in which the key molecular events
      leading to virus reactivation can be studied.

PMID- 22851389
TI  - [Prevention and care of ventilator-associated pneumonia in critically ill
      patients].
AB  - Ventilator-associated pneumonia (VAP) is a hospital-acquired pneumonia that
      occurs in patients usually 48 hours or more after mechanical ventilator
      intubation. VAP is the most common nosocomial infection in critically ill
      patients. Mechanical ventilators are critical oxygenation and ventilation systems
      for patients. However, there is a close relationship among self-use efficacy,
      system settings, and VAP infection rate. VAP not only results in higher
      mortality, longer hospital stays, and higher medical costs, but also negatively
      affects patient outcomes and medical care quality. The purpose of this article
      was to provide reference information on VAP risk factors and prevention measures.

PMID- 22851390
TI  - [Preventing common enteral feeding complications in critically ill adult
      patients].
AB  - Nutritional support provides critically ill patients with energy and nutrients
      required to face the demands of their illness and stress. For those unable to
      ingest orally, enteral feeding rather than parenteral feeding is recommended, as
      the former better preserves gut integrity, reduces risk of infection, and costs
      less. Early enteral feeding in critically ill patients is also associated with
      decreased disease severity, reduced complications, and shortened length of stay.
      Risks associated with enteral feeding include aspiration, diarrhea, vomiting,
      hyponatremia, and hyperglycemia. This article reviews current knowledge on
      enteral feeding and addresses correct feeding tube placement, proper feeding
      sites, assessing and managing gastric residual volume, and preventing feeding
      tube occultation. We also review information related to identifying and
      controlling risk factors for enteral feeding complications such as aspiration,
      diarrhea, vomiting, hyponatremia, and hyperglycemia. Nurses can use this
      information to provide high quality care for enteral feeding patients and develop
      institutional protocols, guidelines, and standards of care for such patients in
      intensive care units.

PMID- 22851391
TI  - [Prevention and management of pressure ulcers in critical patients].
AB  - The Taiwan Join Commission on Hospital Accreditation identified pressure ulcers
      as an important clinical care indicator in 2011. Pressure ulcers are a
      particularly critical medical care issue in hospital intensive care units.
      Pressure ulcers can influence patient physiology in terms of greater perceived
      pain, elevated infection and sepsis incidence, increased unplanned surgical
      treatments, and reduced activities of daily living (ADL). Pressure ulcers can
      also affect psychology through induced depression, stress, and anxiety. They can
      also increase patient and societal costs and prolong hospital stay length. This
      article explores the prevention and management of pressure ulcer in serious
      illness patients and introduces effective assessment and management techniques.
      We hope this article raises clinical nurse awareness of this critical issue and
      helps decrease the incidence of pressure ulcer-related complications in order to
      enhance overall quality of care.

PMID- 22851392
TI  - [Reducing occupational burnout and enhancing job performance in new nurses: the
      efficacy of "last mile" programs].
AB  - BACKGROUND: New nurses undergo a stressful and challenging transition process in
      the nursing workplace. Lack of patient care knowledge and skills and work
      adaption difficulties lead to a high turnover rate that drains essential new
      talent away from the nursing profession and further exacerbates professional
      staffing shortages in the healthcare sector. The "last mile" program is a program
      developed jointly by a nursing school and hospital as a mechanism to bridge
      classroom learning to clinical practice and smooth the transition of nursing
      students into nursing professionals. PURPOSE: The purpose of this study was to
      understand the effect of the "last mile" program on job performance and
      occupational burnout among new nurses. METHODS: We conducted a quasi-experimental
      study in 2009 on a convenience sample of new nurses in a medical center.
      Participants were assigned into two groups, namely those enrolled in the last
      mile program (n = 29) and those not enrolled in the program (n = 94). Research
      team members and several collaborative universities developed the last mile
      program used in this study; Seven experts established content validity; The last
      mile program included 84 hours of lecture courses and 160 hours of clinical
      practice. Data was collected using the nursing job performance scale developed in
      2007 by Greenslade and Jimmieson and translated / back translated into an
      equivalent Chinese version. Exploratory factor analysis showed all items aggraded
      into 8 factors, which could be divided into task performance and contextual
      performance concept categories. Task performance concepts included: social
      support, information, coordination of care, and technical care; Contextual
      performance concepts included: interpersonal support, job-task support,
      volunteering for additional duties and compliance. The Cronbach's alpha for the 8
      factors were .70-.95. The occupational burnout inventory included the 4 subscales
      of personal burnout, work-related burnout, client-related burnout, and over
      commitment, with associated Cronbach's alpha ranging from .84-.90. Data was
      collected at one, three, and six months after employment. Repeated measures ANOVA
      and an independent t-test were used to analyze data. RESULTS: The average age of
      the 123 participants surveyed was 23 years, with no differences identified
      between last-mile and non-last-mile groups in terms of education level, work
      unit, or other demographic variables. New nurses who participated in the last
      mile program achieved significantly higher performance scores for job-task
      support, volunteering for additional duties, and overall task and contextual
      performance than those who did not. Last-mile-program group participants also had
      significantly lower client-related burnout than their non-last-mile-program
      peers. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The last mile program facilitates
      new nurses' contextual performance and reduces incidence of care burnout. The
      cooperative education model linking universities and hospitals can be a positive
      component in a new nurse retention strategy for hospital administrators and
      educators.

PMID- 22851393
TI  - [The effectiveness of multimedia nursing education on reducing illness-related
      anxiety and uncertainty in myocardial infarction patients after percutaneous
      coronary intervention].
AB  - BACKGROUND: Properly educating myocardial infarction (MI) patients in the
      extremely busy cardiac care unit (CCU) work environment is difficult for CCU
      nurses. PURPOSE: This study examined the effectiveness of multimedia nursing
      education in reducing illness-related anxiety and uncertainty in MI patients
      following percutaneous coronary intervention (PCI). METHODS: A quasi-experimental
      study with judgment sampling was designed and performed at a medical center in
      South Taiwan. The control group (n = 36) received written nursing education
      material and the experimental group (n = 40) received multimedia nursing
      education. Participant illness-related anxiety and uncertainty was measured at
      four specific periods, namely (1) at admission to the CCU, (2) immediately after
      completing the nursing education interventions, (3) upon transfer to the general
      ward, and 4) at discharge. Measurement tools included Mishel's uncertainty in
      illness scale (MUIS), the state-trait anxiety inventory (STAI), and noninvasive
      physiological monitoring instruments. RESULTS: Results showed that both
      interventions lowered anxiety / uncertainty in participants with moderate to
      severe levels (experimental group - anxiety: t39 = -6.615, p < .001 and
      uncertainty: t39 = -8.317, p < .001; control group - anxiety: t35 = -4.767, p <
      .001 and uncertainty: t35 = -9.739, p < .001). The experimental group achieved
      significantly greater reductions than the control group in terms of anxiety and
      uncertainty in each of the four measurement periods. CONCLUSIONS / IMPLICATIONS
      FOR PRACTICE: Based on the evidence, both nursing education formats are valid for
      patient education and may be chosen based on CCU clinical conditions.

PMID- 22851394
TI  - [Nurses' self-perception of nursing competence after completing a 2-year training
      program at a medical center].
AB  - BACKGROUND: Taiwan's Department of Health (DOH) promotes a standardized 2-year
      training program to raise the competence of newly certified nurses in the realms
      of patient care, nursing professionalism and communication skills as well as to
      ensure professional nurse training program quality. PURPOSE: This study evaluated
      training program participants' self-perception of nursing competency. METHOD: We
      used a cross-sectional approach and structured questionnaire to evaluate the
      nursing competency of 128 nurse trainees at a medical center. Questionnaires were
      filled out independently by participants and thus reflect participant self
      assessments of questionnaire items. Descriptive and correlation analyses further
      explored data. RESULT: Results showed: mean scores were 3.80 +/- .60 for clinical
      technique; 3.78 +/- .67 for administrative skill; and 3.21 +/- .88 for
      educational and research skills . Nursing ability correlated significantly with
      age, seniority, nursing grade, and courses taken. The relationship between
      participant total score and program completion ratio formed a "V"-shaped
      distribution. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The DOH training program
      was has a positive effect on nursing competency in nurse trainees. Results also
      provide valuable information and suggestions for revising the DOH's nurse
      training program in the future.

PMID- 22851395
TI  - [Associations between stigma perception and stigma coping behavior and quality of
      life in schizophrenic patients treated at a community rehabilitation center].
AB  - BACKGROUND: Quality of life (QOL) is a critical issue in mental health care. The
      associations between quality of life and schizophrenia patients' stigma
      perception and stigma coping behavior are not well understood. PURPOSE: This
      study investigated quality of life in schizophrenia patients. METHODS: We used a
      cross-sectional, correlational research design; enrolled 119 individuals
      diagnosed with schizophrenia as participants; and used instruments including a
      demographics datasheet, perceived stigma scale, stigma coping behavior scale, and
      the World Health Organization quality of life scale, brief version to collect
      data. Data were analyzed using SPSS 12.0 for Windows software. RESULT: (1)
      Participants had an average QOL index score of 62.40, indicating moderate quality
      of life; (2) Long working hours, holding rehabilitation-related employment, and
      receiving social welfare support correlated with lower QOL; (3) Marital issues
      had the greatest impact on quality of life, with participants who chose secrecy /
      concealment reporting generally better QOL; (4) Social welfare support, number of
      working hours, stigma perception, stigma coping, level of job satisfaction, and
      level of salary satisfaction together accounted for 48.8% of total QOL variance.
      CONCLUSIONS: Findings increase our understanding of the influence of socio
      demographics, stigma perception, and stigma coping behavior on quality of life in
      individuals with schizophrenia. Greater community involvement in schizophrenia
      treatment programs can enhance patient satisfaction with their jobs and lives.

PMID- 22851396
TI  - [Improving comprehensiveness of information given to pediatric cardiac surgery
      patients prior to surgery].
AB  - BACKGROUND: Cardiac surgery for critical pediatric patients places significant
      demands on hospital equipment and facilities. Parents of these patients are often
      under enormous stress due to insufficient knowledge regarding cardiac surgery and
      postoperative care procedures. This project used appropriate preoperative
      consultation given by nursing staffs to decrease stress and anxiety in parents of
      pediatric cardiac surgery patients. PURPOSE: This project worked to enhance the
      completion rate of preoperative instructions for pediatric cardiac surgery
      patients and ensure their parents received comprehensive information and
      knowledge. RESOLUTION: The authors developed a standardized procedure for patient
      instruction and evaluation. Participants received instructions in the forms of a
      video presentation and printed handouts. Also, an educational training program
      was held and the implementation of preoperative patient instructions was made a
      routine task during nursing handover to enhance the completion rate. RESULTS: The
      completion rate of patient preoperative instructions to pediatric cardiac surgery
      rose from 78% to 98%; The cognitive degree of participating parents rose from 52%
      to 96%. CONCLUSIONS: This intervention effectively increased the completion rate
      of preoperative instructions for pediatric patients scheduled for cardiac surgery
      and improved clinical pediatric nursing care practicability and efficiency.

PMID- 22851397
TI  - [A program to increase the participation rate in DOTS (Direct Observed Treatment,
      Short course) of Tuberculosis patients in the community].
AB  - BACKGROUND & PROBLEMS: Tuberculosis (TB), a disease subject to mandatory
      reporting, is widely distributed in our country. The Direct Observed Treatment,
      Short-course (DOTS) is an effective protocol to increase TB treatment success.
      PURPOSE: We developed a program in our hospital to increase discharged patient
      participation in DOTS, which helps ensure they receive 6 to 9 months of post
      discharge medication therapy to maximize treatment outcomes. RESOLUTION: We
      identified four key problems related to low TB patient participation in DOTS.
      These included (1) patients did not understand the DOTS program; (2) staff did
      not know how to conduct the DOTS protocol; (3) staff had not received in-service
      DOTS education; and (4) the hospital had no DOTS patient education or teaching
      aids available. To improve TB patient participation in DOTS, we revised patient
      education material, provided continuing education to nursing staff, invited
      physicians and community co-workers to join in the outreach program, and made
      posters to remind discharged patients to sign up for the DOTS program. RESULTS:
      Patient participation in DOTS rose from 27.1% to 96.3% and nursing staff
      knowledge of DOTS rose from 86.3% to 100%. CONCLUSIONS: This program effectively
      increased TB patient motivation to join DOTS after hospital discharge and also
      improved successful recovery and treatment completion rates. Increasing post
      discharge TB patient participation in the DOTS protocol is an effective strategy
      for achieving the national goal of reducing TB cases by 50% within ten years.

PMID- 22851398
TI  - [Clinical teaching program: standardized operating procedure for intra-aortic
      balloon pump support].
AB  - Intra-aortic balloon pump (IABP) is one of the most important treatment
      strategies for patients with heart failure in the intensive care unit (ICU). To
      ensure quality of treatment, clinical preceptors must employ effective teaching
      strategies to acquaint nurses with the proper use of IABPs. Many nurses are
      hesitant to use IABPs due to lack of knowledge regarding their use. Classroom
      lectures and instruction manual-style materials are often ineffective strategies
      for teaching novice nurses to use IABPs properly and have resulted in
      unsatisfactory patient treatment quality. This study developed a creative, pithy
      rhyme to help nurses remember the key elements of IABP support as part of their
      IABP learning process. This innovative tool uses rhymes and mental images to
      instill critical information related to IABP use and help nurses become fluent
      IABP users.

PMID- 22851399
TI  - [Percutaneous endoscopic gastrostomy (PEG): overview and nursing care].
AB  - The dramatic increase in the elderly population in Taiwan has made dysphagia an
      increasingly prevalent problem in long-term care. While tube feeding is mandatory
      for patients unable to take food orally, this approach increases recurrent
      aspiration pneumonia and malnutrition risks. Percutaneous endoscopic gastrostomy
      (PEG) is currently the most effective and prevalent approach to enteral
      nutrition. This article introduces the definition, indications,
      contraindications, complications, advantages and disadvantages of PEG and its
      clinical nursing care protocols. The author hopes that this narrative description
      of a nurse's experience providing appropriate nursing care to a PEG patient will
      help enhance reader understanding of PEG care.

PMID- 22851400
TI  - [Concept analysis of feelings of loss among elderly nursing home residents].
AB  - Loss is a phenomenon common to the human experience. Feelings of loss represent
      an emotional response to separation from subjectively important person(s) or
      things. Loss often leaves nursing home elderly residents feeling abandoned,
      insecure, lonely, and hopeless and may affect their perception of the meaning of
      life. Those who are unable to adjust may slip into a depressed mood, which may
      lead to suicidal ideations. No systematic analysis of loss has been conducted.
      The purpose of this paper is to expand understanding of the concept of loss. The
      authors intend to clarify the defining attributes of loss, identify the
      antecedents that influence the perception of loss and discuss the possible
      consequences of loss using Walker and Avant's (2005) concept analysis. A model
      case is used to demonstrate how loss is tied to these critical attributes.
      Borderline and contradictory cases are presented to differentiate between the
      concept of loss and other concepts. It is believed that this analysis will help
      nursing staff to gain a better understanding of the concept of loss and help them
      apply this knowledge in clinical practice.

PMID- 22851401
TI  - [Clinical ethic dilemmas and difficulties in reporting child abuse].
AB  - The number of reported cases of child abuse has been rising steadily in Taiwan.
      Although child abuse reporting is mandatory for healthcare professionals, Taiwan
      specific social norms and traditional cultural values make the decision to report
      such abuse more complex and difficult. We used Jonsen's four topics method to
      examine a suspected case of child abuse and to analyze its associated dilemmas
      and ethical difficulties. We then discussed the identified conflicts among the
      three aspects of cultural values, legal obligations, and personal values.
      Findings indicate that healthcare professionals experience dilemmas among these
      three aspects. Reporting suspected child abuse appears the best resolution after
      considering and balancing the principles of non-malfeasance, beneficence,
      fidelity and follow-up care. Once reported, resources can be provided to the
      affected child and his / her family. This case analysis provides a reference for
      healthcare professionals to deal with child abuse cases.

PMID- 22851402
TI  - Genotypic association of the DAOA gene with resting-state brain activity in major
      depression.
AB  - Compelling evidence suggests that the glutamatergic system may contribute to the
      pathophysiology of major depression (MDD). While the D-amino acid oxidase
      activator (DAOA) gene can affect glutamatergic function, its genetic associations
      with MDD and abnormal resting-state brain activity have yet to be elucidated. A
      total of 488 patients with MDD and 480 controls were recruited to examine MDD
      association for the DAOA gene in a Chinese population, of whom 53 medication-free
      patients and 46 well-matched controls underwent resting-state functional magnetic
      resonance imaging for regional homogeneity (ReHo) analysis. The differences in
      ReHo between genotypes of interest were initially tested by the Student's t test,
      and the 2 * 2 (genotypes * disease status) ANOVA was then performed to identify
      the main effects of genotypes, disease status, and their interactions in MDD.
      Allelic association of the DAOA gene with MDD was observed for rs2391191,
      rs3918341, and rs778294 and haplotypic association for 2- and 3-SNP haplotypes.
      Six clusters in the cerebellum, right middle frontal gyrus and left middle
      temporal gyrus showed genotypic association between altered ReHo and rs2391191.
      The main effects of rs2391191 genotypes were found in the right culmen and right
      middle frontal gyrus. The left uvula and left middle temporal gyrus showed a
      genotypes * disease status interaction. Our results suggest that the DAOA gene
      may confer genetic risk of MDD. Genotypic effect of rs2391191 and its interaction
      with disease status may contribute to the altered ReHo in patients with MDD.
      Glutamatergic modulation may play an important role in alteration of the resting
      state brain activities.

PMID- 22851403
TI  - HCCRBP-3 induces tumorigenesis through direct interaction with HCCR-1 in human
      cancers.
AB  - Human cervical cancer oncogene 1, HCCR-1, is over-expressed in various human
      tumors and appears to serve as a negative regulator of the p53 gene. HCCR-1
      transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes
      to tumorigenesis. We identified the HCCR-1 binding protein 3 (HCCRBP-3) as a
      binding partner for HCCR-1. These two proteins co-localized to the mitochondria.
      HCCRBP-3 over-expressed in various human tumors converted normal cells into tumor
      cells in vitro. Nude mice injected with NIH/3T3 cells stably transfected with
      HCCRBP-3 also induced the tumor formation. In addition, p53 showed the functional
      impairment in HCCRBP-3-transfected cells as accompanied with defective induction
      of p21 and bax. In support of this, p21 promoter activities containing p53
      responsive elements were inhibited by HCCRBP-3 in a dose-dependent manner.
      Therefore, our study suggests that HCCRBP-3 contributes to the HCCR-1 induced
      tumorigenesis by interrupting the p53 function.

PMID- 22851404
TI  - Invited commentary on the article, the title "surgical correction of giant
      extracardiac unruptured aneurysm of the right coronary sinus of Valsalva: case
      report and review of the literature".

PMID- 22851405
TI  - Transaortic edge-to-edge mitral valve repair and left ventricular myectomy.
AB  - Systolic anterior motion of mitral anterior leaflet is a serious clinical
      condition and it is hard to control medically. Alfieri edge-to-edge repair has
      been thought one of the useful techniques to improve abnormal anterior systolic
      motion with hypertrophic obstructive cardiomyopathy. Here, we present a 71-year
      old lady who had the left ventricular outflow tract obstruction, severe mitral
      valve regurgitation with systolic anterior motion. The patient had a history of
      aortic valve replacement 5 years ago. She was successfully treated with
      transaortic edge-to-edge mitral valve plasty and myectomy of the left ventricle.
      Postoperative course was uneventful.

PMID- 22851406
TI  - Clinical benefit in patients with metastatic bone disease: results of a phase 3
      study of denosumab versus zoledronic acid.
AB  - BACKGROUND: Patients with metastatic bone disease are living longer in the
      metastatic stage due to improvements in cancer therapy, making strategies to
      prevent the aggravation of bone disease and its complications, such as skeletal
      related events (SREs) and pain, increasingly important. PATIENTS AND RESULTS: In
      this phase 3 trial in patients with advanced cancer (excluding breast and
      prostate cancer) or multiple myeloma, denosumab reduced the risk of radiation to
      bone by 22% relative to zoledronic acid (P = 0.026), prevented worsening of pain
      and pain interference (2-point increase in Brief Pain Inventory score; P < 0.05
      versus zoledronic acid), and reduced the frequency of a shift from no/weak opioid
      analgesic use to strong opioids (P < 0.05 versus zoledronic acid at months 3-5).
      Denosumab delayed the time to moderate-to-severe pain compared with zoledronic
      acid in patients with mild or no pain at the baseline (P = 0.04), supporting
      early treatment. Health-related quality-of-life scores were similar in both
      groups. The number needed to treat to avoid one SRE for denosumab was 3 patient
      years versus placebo and 10 patient-years versus zoledronic acid. CONCLUSION: The
      use of denosumab was associated with better prevention of the complications of
      metastatic bone disease secondary to solid tumors or multiple myeloma versus
      zoledronic acid.

PMID- 22851407
TI  - Phase II study of bevacizumab with liposomal doxorubicin for patients with
      platinum- and taxane-resistant ovarian cancer.
AB  - BACKGROUND: Suppression of neoangiogenesis and pegylated liposomal doxorubicin
      (PLD) each contribute to the management of platinum-resistant/refractory ovarian
      cancer. The aim of this study is to test the combination of bevacizumab and PLD
      in women with resistant or refractory ovarian cancer. METHODS: Eligibility
      criteria were no more than two prior treatments with platinum-containing regimens
      and one additional regimen, without anthracyclines. Treatment was administered
      every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The
      primary end point was progression-free survival (PFS) at 6 months; the secondary
      end points included side-effects, overall response rates (ORR) and survival (OS).
      RESULTS: Forty-six patients were enrolled. The average number of courses
      administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according
      to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range
      2-13.3 months) according to Response Evaluation Criteria in Solid Tumors
      (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2%
      [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was
      86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions
      (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects
      included hypertension, headache, renal dysfunction and proteinuria, wound healing
      delay, and one episode each of central nervous system (CNS) ischemia and
      hemolytic uremic syndrome. CONCLUSION: PLD with bevacizumab has improved activity
      in recurrent ovarian cancer with increased toxicity.

PMID- 22851408
TI  - Ultrashort echo time MR imaging with off-resonance saturation for
      characterization of pathologically altered Achilles tendons at 3 T.
AB  - Off-resonance radiofrequency saturation pulses applied prior to regular
      excitation in MR sequences can be used to modify signal contrast based on
      magnetization transfer and direct saturation effects. Clinical applicability and
      value of ultrashort echo time sequences combined with off-resonance saturation
      pulses was tested in 16 healthy and 14 tendinopathic as well as paratendinopathic
      Achilles tendons in vivo at 3 T. A 3D ultrashort echo time sequence in
      combination with a gaussian off-resonance saturation pulse (frequency offset:
      1000-5000 Hz) was used to modify the detectable MR signal intensity from the
      Achilles tendon. Off-resonance saturation ratio was calculated as the relative
      reduction in signal intensity under selective off-resonance saturation in
      relation to a reference measurement without any saturation pulse. Off-resonance
      saturation ratio in tendons of healthy volunteers ranged from 0.52 +/- 0.06 (1000
      Hz) to 0.24 +/- 0.02 (5000 Hz), whereas symptomatic tendinopathic tendons (0.35
      +/- 0.04 to 0.17 +/- 0.02) and asymptomatic tendinopathic tendons (0.41 +/- 0.06
      to 0.21 +/- 0.02) showed significantly lower mean off-resonance saturation ratio
      values. Off-resonance saturation ratio values might provide a sensitive and
      quantitative marker for assessment of pathological microstructure alterations of
      the Achilles tendon.

PMID- 22851409
TI  - Noninvasive classification of hepatic fibrosis based on texture parameters from
      double contrast-enhanced magnetic resonance images.
AB  - PURPOSE: To demonstrate a proof of concept that quantitative texture feature
      analysis of double contrast-enhanced magnetic resonance imaging (MRI) can
      classify fibrosis noninvasively, using histology as a reference standard.
      MATERIALS AND METHODS: A Health Insurance Portability and Accountability Act
      (HIPAA)-compliant Institutional Review Board (IRB)-approved retrospective study
      of 68 patients with diffuse liver disease was performed at a tertiary liver
      center. All patients underwent double contrast-enhanced MRI, with histopathology
      based staging of fibrosis obtained within 12 months of imaging. The MaZda
      software program was used to compute 279 texture parameters for each image. A
      statistical regularization technique, generalized linear model (GLM)-path, was
      used to develop a model based on texture features for dichotomous classification
      of fibrosis category (F <=2 vs. F >=3) of the 68 patients, with histology as the
      reference standard. The model's performance was assessed and cross-validated.
      There was no additional validation performed on an independent cohort. RESULTS:
      Cross-validated sensitivity, specificity, and total accuracy of the texture
      feature model in classifying fibrosis were 91.9%, 83.9%, and 88.2%, respectively.
      CONCLUSION: This study shows proof of concept that accurate, noninvasive
      classification of liver fibrosis is possible by applying quantitative texture
      analysis to double contrast-enhanced MRI. Further studies are needed in
      independent cohorts of subjects.

PMID- 22851410
TI  - The impetus theory in judgments about object motion: a new perspective.
AB  - Several tendencies found in explicit judgments about object motion have been
      interpreted as evidence that people possess a naive theory of impetus. The theory
      states that objects that are caused to move by other objects acquire force that
      determines the kind of motion exhibited by the object, and that this force
      gradually dissipates over time. I argue that the findings can better be
      understood as manifestations of a general understanding of externally caused
      motion based on experiences of acting on objects. Experiences of acting on
      objects yield the idea that properties of the cause of motion are transmitted to
      the effect object. This idea functions as a heuristic for explicit predictions of
      object motion under conditions of uncertainty. This accounts not only for the
      findings taken as evidence for the impetus theory, but also for several findings
      that fall outside the scope of the impetus theory. It has also been claimed that
      judgments about the location at which a moving object disappeared are influenced
      by the impetus theory. I argue that these judgments are better explained in a
      different way, as best-guess extrapolations made by the visual system as a
      practical guide to interactions with the object, such as interception.

PMID- 22851411
TI  - Refining psychiatric phenotypes for response to treatment: contribution of LPHN3
      in ADHD.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder
      characterized by inappropriate levels of attention, hyperactivity, and
      impulsivity. Although a strong genetic component to the disorder has been
      established, the molecular genetic underpinnings of this disorder remain elusive.
      Recently, several studies have reported an association between polymorphisms
      within the latrophilin 3 gene (LPHN3) and ADHD. Interestingly, the same single
      nucleotide polymorphism conferring susceptibility to ADHD has also been found to
      predict efficacy of stimulant medication in children. The main objectives of the
      current article are: (i) To tackle the phenotype heterogeneity issue in ADHD by
      defining an objective and quantitative measure of response to treatment in a
      sample of ADHD children based on a hand held automatic device (Actiwatch) and
      (ii) to use this measure to reproduce for the first time the association between
      LPHN3 variants and response to methylphenidate (MPH) using a double-blind,
      placebo-controlled crossover experimental design. The results of our study
      confirm the hypothesis that LPHN3 is associated with response to MPH in ADHD
      children. Although this will require further validation, our work suggests that
      the use of an objective measure of response to treatment, such as the change in
      the child's motor activity measured by Actiwatch, has the potential to uncover
      genetic association signals that in some conditions might not be obtained using
      more subjective measures, such as the clinical consensus rating, for example.

PMID- 22851412
TI  - Outcomes from a mentored research boot camp: Focused Investigator Training (FIT)
      Program.
AB  - STUDY OBJECTIVE: To evaluate the change in mentee self-efficacy with regard to
      research, number of grant submissions, and total amount of new monies awarded to
      graduates of a novel, mentored, investigator-training program-the Focused
      Investigator Training (FIT) Program. DESIGN: Retrospective observational
      analysis. SETTING: American College of Clinical Pharmacy Research Institute.
      PARTICIPANTS: Fifty-five mentees from the 2008, 2009, 2010, and 2011 FIT
      Programs. INTERVENTION: The FIT Program is a novel, intensive, 5-day, mentored
      development "boot camp" for mid-career investigators holding research-intensive
      positions. The program consists of proposal groups of two mentors and two-four
      mentees, one-on-one office hours, lectures, panel discussions, directed readings,
      and small group sessions. Twelve highly successful researchers and
      biostatisticians were recruited as mentors. Mentees submitted a detailed proposal
      and received faculty feedback before the program. MEASUREMENTS AND MAIN RESULTS:
      The main outcomes of the FIT Program were mentee self-efficacy with regard to
      research, number of grant submissions, and total amount of new monies awarded to
      2008 and 2009 FIT Program graduates. Univariate statistical analysis was
      conducted to determine characteristics of those FIT attendees with subsequent
      successful grantsmanship. A combined measure of self-confidence in successful
      grantsmanship was significantly increased after completion of the FIT program.
      More than $2.7 million was funded to FIT graduates as principal investigators,
      and as coinvestigators or subcontractors, an additional $382,000 was awarded in
      new funds. Seven mentees from the 2008 and 2009 classes received new federal
      funding, mostly through various K-type award mechanisms. CONCLUSION: The FIT
      Program was associated with a significant increase in attendees' self-efficacy
      for obtaining external research funding. Program attendance was associated with
      numerous successfully funded grants by pharmacist investigators. Future FIT
      Program success hinges on attracting adequate numbers of qualified applicants.

PMID- 22851414
TI  - Languages are scientific workplaces and not simply vehicles for scientific ideas.

PMID- 22851413
TI  - Complement fragment C3d is colocalized within the lipid rafts of T cells and
      promotes cytokine production.
AB  - The complement system plays an important role in tissue inflammation and damage
      in SLE patients. High levels of C3d were detected on the surface of erythrocytes
      and lymphocytes of SLE patients. The objective of this study was to assess the
      functional consequences of C3d fragments deposited on the surface membrane of SLE
      T cells. METHODS: 46 SLE patients, 43 patients with other autoimmune diseases
      (OAD) and 33 healthy individuals (N) were enrolled in this study. T cells were
      isolated from peripheral blood and flow cytometry studies were conducted to
      assess the levels of C3d fragments, Ca++ influx responses and cytokine
      production. Confocal microscopy was used to study co-localized molecules.
      Student's t-test was performed to determine statistical significance among study
      groups. RESULTS: A significant percentage of the SLE T cells were found to be
      positive for C3d (13.58 +/- 3.92%) when compared with normal T cells (4.52 +/-
      2.92%) (p < 0.0000547) and T cells from patients with other autoimmune diseases
      (6.31 +/- 4.57%) (p < 0.00513). Peak Ca++ influx responses were significantly
      higher in C3d- SLE T cells compared with C3d+ SLE T cells (p < 0.011). C3d+ T
      cells produced significantly more IL-2, IFN-gamma, IL-4 and IL-17. In contrast to
      the increased production of IL-2 by the C3d+ T cells, the overall SLE T cell
      population produced less IL-2 when compared with T cells from normal individuals
      or patients with other autoimmune disease. The C3d fragments were found to be
      localized within the lipid rafts. CONCLUSION: C3d fragments are localized in the
      lipid rafts of SLE T cells and contribute to abnormal T cell function by
      modulating Ca++ influx responses and increased cytokine production.

PMID- 22851415
TI  - [Logic, probability and rhetoric in legal argumentation].
AB  - Judicial reasoning has often been seen as mere rhetoric. Yet, as I argue here,
      this reasoning actually stems from the exigencies of truth. This in turn requires
      questioning the relationship between logic and rhetoric in the legal field. The
      logic referred to is probability, which is most appropriate to pragmatic
      rationality. Hence, to shed light on judicial reasoning, this essay puts the
      relationship between judicial logic and probabilistic logic in historical
      perspective whilst taking into account the existing literature on the topic.

PMID- 22851416
TI  - [Constructing a language for social sciences: Condorcet's Tableau historique].
AB  - Condorcet started working on "social sciences" many years before the French
      Revolution. Although published in 1793-1794, his Tableau historique, was first
      conceived in the 1770s. It examined the necessary conditions for scientific
      reasoning and scientific languages. Analyzing the obstacles that stood in the way
      of the development of social sciences, Condorcet used case studies to offer a
      reflection on the making of a language that would be scientific and accessible to
      the enlightened citizen as well.

PMID- 22851417
TI  - [Analytical philosophy or the search for a technological thought].
AB  - This article focuses on the origins of analytical philosophy. It argues that the
      conditions under which it was thought out were similar to the conditions
      necessary for critical thinking - like the scientific inquiry that served as its
      model, analytical philosophy was based on the distinction between syntax and
      semantics. Resulting from logical analysis, this distinction was later essential
      to all systems of representation - works of art, human action, intellectual
      endeavours. This evolution reveals a major concern - the need for a technical
      tool for the critical mind.

PMID- 22851418
TI  - [Not Available].

PMID- 22851420
TI  - [Not Available].

PMID- 22851419
TI  - [What's new in general sociology ? (Second Part)].
AB  - Over the last two decades, history and social sciences have experienced a kind of
      merging, and a vast number of specialized domains have emerged. Yet the
      durkheimian register of "general sociology" seems somehow neglected. Firstly,
      this article analyzes the reasons for this neglect, and secondly, it indicates
      how, through a long-term reflexivity, one can formulate a new agenda for general
      sociology.

PMID- 22851421
TI  - [Not Available].

PMID- 22851422
TI  - High junction and twin boundary densities in driven dynamical systems.
AB  - A novel mechanism for the generation of device materials with very high domain
      boundary densities is described: we shear the sample in a computer experiment and
      achieve higher twin densities than in rapid quench. These domain patterns are
      very stable. Elastically soft materials (image with 6.4$ ?times $10(5)  atoms)
      has greater twin densities than hard materials, even for nano-crystals.

PMID- 22851423
TI  - Computational and experimental studies of an orthopedic implant: MRI-related
      heating at 1.5-T/64-MHz and 3-T/128-MHz.
AB  - PURPOSE: To use numerical modeling to predict the worst-case of magnetic
      resonance imaging (MRI)-induced heating of an orthopedic implant of different
      sizes under 1.5-T/64-MHz and 3-T/128-MHz conditions and to apply the experimental
      test to validate the numerical results for worst-case heating. MATERIALS AND
      METHODS: Investigations of specific absorption rate (SAR) and the temperature
      rise of an orthopedic implant of different sizes within a standard phantom were
      accomplished by numerical finite-difference time-domain modeling and experimental
      measurements. MRI-related heating experiments were performed using standardized
      techniques at 1.5-T/64-MHz and 3-T/128-MHz. RESULTS: The numerical modeling
      results indicated that the induced energy deposition is almost linearly related
      to the dimension of the orthopedic implant when it is less than 100 mm for 1.5
      T/64-MHz and 3-T/128-MHz conditions. At 3-T/128-MHz, when the dimension is
      greater than 100 mm, the linear relation does not exist, which suggests a
      wavelength effect at higher frequency. Higher temperature rises occurred at 1.5
      T/64-MHz MRI than at 3-T/128-MHz for both numerical modeling and experimental
      studies. CONCLUSION: The numerical technique predicted which device size had
      maximum heating and its location. Temperature rise data agreed well with thermal
      simulation results. The presented method proved to be suitable to assess MRI
      induced heating of complex medical implants.

PMID- 22851424
TI  - A validated HPLC assay method for the determination of sodium alginate in
      pharmaceutical formulations.
AB  - A high-performance liquid chromatography-diode array detector method was
      developed and validated for the quantification of sodium alginate in antacid oral
      suspension using a phenyl stationary phase and buffer solution at pH 7.0 as a
      mobile phase. The method was validated for specificity, linearity, range,
      accuracy, precision and robustness. The method was specific for the determination
      of sodium alginate in the bulk drug, pharmaceutical dosage form and under stress
      degradation. The method was linear over the range of 600 to 1,400 ug/mL with r(2)
      = 0.9999, and accuracy and precision were acceptable with relative standard
      deviation < 2.0%. The described method is simple, specific, precise, accurate,
      robust and stability-indicating, and can be successfully applied for the routine
      analysis of sodium alginate in bulk drug and pharmaceutical dosage form.

PMID- 22851425
TI  - Development of HPLC methods for the determination of vancomycin in human plasma,
      mouse serum and bronchoalveolar lavage fluid.
AB  - Two high-performance liquid chromatography methods utilizing a protein
      precipitation technique were developed to analyze vancomycin in human plasma,
      mouse serum and bronchoalveolar lavage (BAL) fluid. The mobile phase consisted of
      ammonium phosphate buffer with acetonitrile. A cross-matrix validation was
      performed to ensure that the mouse serum was comparable to the original
      biological matrix of human plasma. Murine BAL samples were run on a saline
      standard curve. For saline samples, the mobile phase from the human plasma study
      was used with the addition of 1M sodium hydroxide (0.2%) to avoid interfering
      peaks. A reversed-phase column was used with an ultraviolet detector set at 240
      nm for human plasma and 198 nm for saline to increase peak size. The standard
      curves were liner over the ranges of 1 to 80 ug/mL for human plasma and 0.1 to 10
      ug/mL for saline. These assays are simple, reproducible and accurate. These
      analytical techniques were successfully applied to analyze vancomycin
      concentrations in mouse serum and BAL samples.

PMID- 22851426
TI  - Increasing signal homogeneity and image quality in abdominal imaging at 3 T with
      very high permittivity materials.
AB  - The appearance of severe signal drop-outs in abdominal imaging at 3 T arises
      primarily from areas of very low B1+ transmit field in the body, and is
      problematic in both obese as well as very thin subjects. In this study, we show
      how thin patient-friendly pads containing new high permittivity materials can be
      designed and optimized, and when placed around the subject increase substantially
      the B1+ uniformity and the image quality. Results from nine healthy volunteers
      show that inclusion of these dielectric pads results in statistically significant
      decreases in the coefficient of variance of the B1+ field, with stronger and more
      uniform fields being produced. In addition there are statistically significant
      decreases in time-averaged power required for scanning. These differences are
      present in both quadrature-mode operation (coefficient of variance decrease,
      P<0.0001, mean 25.4+/-10%: power decrease, P=0.005, mean 14+/-14%) and also for
      the RF-shimmed case (coefficient of variance decrease, P=0.01, mean 16+/-13%:
      power decrease, P=0.005, mean 22+/-11%) of a dual-transmit system.

PMID- 22851427
TI  - The defect in humoral immunity in patients with Nijmegen breakage syndrome is
      explained by defects in peripheral B lymphocyte maturation.
AB  - Patients with an immunodeficiency in the course of Nijmegen breakage syndrome
      (NBS) that is caused by mutations in the NBN/NBS1 gene are prone to recurrent
      infections and malignancies, due to a defective DNA double-strand breaks repair
      mechanism. Four-color flow cytometry was used to analyze changes in B lymphocyte
      subsets reflecting the most important stages of peripheral B cell maturation. It
      was demonstrated that the humoral immune defect observed in NBS patients was
      caused by reduced numbers of B lymphocytes, but also by their aberrant
      maturation. Reduced relative and absolute counts of naive and memory B cells were
      accompanied by a significant accumulation of the natural effector B lymphocytes.
      The elevated proportion of IgM-only memory and reduced proportion of IgM-negative
      cells within the memory B cell pool suggests that there is class-switch
      recombination defect in this population of cells in NBS patients, resulting in
      inadequate production of immunoglobulins. Because of the reduced T-cell counts,
      the T-cell dependent antigen response is severely impaired resulting in a lower
      frequency of memory B-cells. The T-cell independent B-cell differentiation
      pathway seems less affected. The reduced IgG and IgA levels in patients with NBS
      are caused both by ineffective class switch, at least due to poor T cell help,
      and low number of memory B cells. This study illustrates that the NBN gene
      product nibrin plays an important role at different levels in the B-cell system.

PMID- 22851428
TI  - Effect of therapeutic doses of acetaminophen (up to 4 g/day) on serum alanine
      aminotransferase levels in subjects consuming ethanol: systematic review and meta
      analysis of randomized controlled trials.
AB  - STUDY OBJECTIVE: To quantify the effect of therapeutic doses of acetaminophen on
      serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol.
      DESIGN: Systematic review of six randomized placebo-controlled trials, of which
      five were included in a meta-analysis. SUBJECTS: Subjects included in the meta
      analysis were those who consumed ethanol and received acetaminophen in doses up
      to 4 g/day (551 subjects) or placebo (350 subjects). MEASUREMENTS AND MAIN
      RESULTS: A comprehensive literature search of the MEDLINE, EMBASE, and
      International Pharmaceutical Abstracts databases and the Cochrane Central
      Register of Controlled Trials was performed to identify randomized, placebo
      controlled trials that enrolled subjects who consumed ethanol, received
      acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level
      measurements. A total of 184 articles were identified; six articles met all
      criteria. Five of the six articles reported ALT levels on study day 4 for both
      groups of subjects who received acetaminophen or placebo. Thus, for the meta
      analysis, we used the primary outcome of mean change in serum ALT level from
      baseline to day 4 in the acetaminophen groups compared with the placebo groups.
      We found that the difference in mean change from baseline ALT levels between the
      acetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval 
      0.2-0.1 U/L). There were no reports of liver dysfunction, liver failure, or death
      in any of the trials. CONCLUSION: In randomized, placebo-controlled trials of
      subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted
      when subjects ingested up to 4 g/day of acetaminophen.

PMID- 22851430
TI  - Mastitis severity induced by two Streptococcus uberis strains is reflected by the
      mammary immune response in vitro.
AB  - Streptococcus uberis is the most common environmental mastitis pathogen causing
      udder inflammations of different severities in dairy cows. The aim of the study
      was to investigate if the different clinical outcome of mastitis induced by
      different strains of S. uberis can be reflected in the mammary immune response.
      Mammary epithelial cells and somatic milk cells were treated with heat
      inactivated and living S. uberis of strain A and strain B in vitro. Strain A was
      repeatedly isolated from a chronically infected quarter during 8 months, and
      persisted in the quarter despite antibiotic treatment. Strain B caused an acute
      clinical mastitis and was not further isolated after a single antibiotic
      treatment. Treatment with Strain B induced a more pronounced increase of mRNA
      expression of various immune factors (interleukin-8, interleukin-1beta, RANTES,
      and lactoferrin) in mammary epithelial cells than strain A. In contrast to
      mammary epithelial cells the response of removed somatic milk cells showed no
      differences between the stimulation with two S. uberis strains. Tumor necrosis
      factor-alpha mRNA expression was not differently induced by the two strains. In
      conclusion, the characteristics of different severities of mastitis that are
      induced by different S. uberis strains in vivo can also be reflected at the level
      of the immune response of the mammary gland in vitro.

PMID- 22851431
TI  - Application of the Sequential Organ Failure Assessment Score to predict outcome
      in critically ill dogs: preliminary results.
AB  - In human medicine the Sequential Organ Failure Assessment (SOFA) score is one of
      the most commonly organ dysfunction scoring systems used to assess critically ill
      patients and to predict the outcome in Intensive Care Units (ICUs). It is
      composed of scores from six organ systems (respiratory, cardiovascular, hepatic,
      coagulation, renal, and neurological) graded according to the degree of the
      dysfunction. The aim of the current study was to describe the applicability of
      the SOFA score in assessing the outcome of critically ill dogs. A total of 45
      dogs admitted to the ICU was enrolled. Among these, 40 dogs completed the study:
      50 % survived and left the veterinary clinic. The SOFA score was computed for
      each dog every 24 hours for the first 3 days of ICU stay, starting on the day of
      admission. A statistically significant correlation between SOFA score and death
      or survival was found. Most of the dogs showing an increase of the SOFA score in
      the first 3 days of hospitalization died, whereas the dogs with a decrease of the
      score survived. These results suggest that the SOFA score system could be
      considered a useful indicator of prognosis in ICUs hospitalized dogs.

PMID- 22851432
TI  - [Squamous cell carcinoma of the reticulum and liver in a Simmental cow].
AB  - This report describes an 8.8-year-old Simmental cow with squamous cell carcinoma
      of the reticulum and liver. The cow had calved recently and was referred to our
      clinic because of intractable fever, anorexia and progressive indigestion. The
      general condition and mental status were moderately affected and rectal
      temperature and respiratory rate were significantly elevated. There were no
      ruminal sounds and pinching of the withers consistently elicited a grunt. Serum
      activities of gamma glutamyl transferase, glutamate dehydrogenase and sorbitol
      dehydrogenase were elevated. Radiographic examination of the reticulum and
      ultrasonographic examination of the reticulum, liver and abdominal cavity
      revealed multifocal, poorly demarcated, heterogeneous and echogenic changes in
      the liver. Biopsy of these lesions yielded a diagnosis of squamous cell
      carcinoma. The cow was euthanized and a postmortem examination confirmed the
      diagnosis. A 15 by 15 cm neoplasm was found in the reticular wall, and
      histological examination showed squamous cell carcinoma. It was assumed that the
      reticular mass was the primary tumour, which metastasized to the liver via the
      portal vein.

PMID- 22851433
TI  - Endoprosthesis (EN) in frontlimb-sparing surgery for distal radial tumours in the
      dog: preliminary results.
AB  - In veterinary medicine, limb-sparing techniques are most implemented when the
      uninvolved limbs are affected by other orthopaedic or neurological disorders, in
      large breeds or when the owner declines amputation. This report describes the
      surgical technique used for implantation of an endoprosthesis following tumour
      resection in the distal radius in 3 dogs using both standard and angle-stable
      plates. Endoprosthesis offers an easy and readily available surgical alternative
      to cortical allografts. Despite post-operative complications, this technique
      resulted in a good quality of life in all 3 dogs.

PMID- 22851434
TI  - [Milbemycinoxime intoxication in a Miniature Australian Shepherd dog].
AB  - A 3-year-old female intact Miniature Australian Shepherd presented with
      convulsive status epilepticus after milbemycinoxime administration in the
      recommended dosage. In addition to continuous intravenous antiepileptic therapy
      the dog had to be ventilated for 36 hours due to aspiration pneumonia. After
      extubation control of intermittent tonic-clonic seizures required a constant-rate
      infusion of propofol for another 96 hours, before it could be discontinued on day
      5. The patient had fully recovered by day 10. The dog was known to be homozygous
      for the MDR1-gene mutation. So far milbemycinoxime was regarded a save drug in
      MDR1-deficient dogs. However, the present case suggests using the lowest possible
      dosage in MDR1-deficient dogs and pet owners should be advised of potential
      complications.

PMID- 22851435
TI  - Sanitation of European Foul Brood in Werdenberg District, Switzerland: a field
      experiment.

PMID- 22851440
TI  - Large work function shift of gold induced by a novel perfluorinated azobenzene
      based self-assembled monolayer.
AB  - Tune it with light! Self-assembled monolayers on gold based on a chemisorbed
      novel azobenzene derivative with a perfluorinated terminal phenyl ring are
      prepared. The modified substrate shows a significant work function increase
      compared to the bare metal. The photo-conversion between trans and cis isomers
      chemisorbed on the surface shows great perspectives for being an accessible route
      to tune the gold properties by means of light.

PMID- 22851429
TI  - Receptor type protein tyrosine phosphatases (RPTPs) - roles in signal
      transduction and human disease.
AB  - Protein tyrosine phosphorylation is a fundamental regulatory mechanism
      controlling cell proliferation, differentiation, communication, and adhesion.
      Disruption of this key regulatory mechanism contributes to a variety of human
      diseases including cancer, diabetes, and auto-immune diseases. Net protein
      tyrosine phosphorylation is determined by the dynamic balance of the activity of
      protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Mammals
      express many distinct PTKs and PTPs. Both of these families can be sub-divided
      into non-receptor and receptor subtypes. Receptor protein tyrosine kinases
      (RPTKs) comprise a large family of cell surface proteins that initiate
      intracellular tyrosine phosphorylation-dependent signal transduction in response
      to binding of extracellular ligands, such as growth factors and cytokines.
      Receptor-type protein tyrosine phosphatases (RPTPs) are enzymatic and functional
      counterparts of RPTKs. RPTPs are a family of integral cell surface proteins that
      possess intracellular PTP activity, and extracellular domains that have sequence
      homology to cell adhesion molecules. In comparison to extensively studied RPTKs,
      much less is known about RPTPs, especially regarding their substrate
      specificities, regulatory mechanisms, biological functions, and their roles in
      human diseases. Based on the structure of their extracellular domains, the RPTP
      family can be grouped into eight sub-families. This article will review one
      representative member from each RPTP sub-family.

PMID- 22851441
TI  - Social identification structures the effects of perspective taking.
AB  - Researchers who study perspective taking are generally optimistic about the
      potential for interventions to improve intergroup perceptions. The current
      research provides new insight into the conditions that frame the intergroup
      outcomes of perspective taking. The results show that the effects of perspective
      taking are not always positive but depend on perspective takers' degree of
      identification with the in-group. In two experiments, we demonstrated that
      adopting the perspective of an out-group member can have damaging effects on
      intergroup perceptions among group members who are highly identified with the in
      group. Specifically, compared with less committed members, those who identified
      highly with the in-group used a greater number of negative traits to describe the
      out-group following perspective taking. Such perspective taking also led
      participants with high in-group identification to judge the out-group less
      favorably. Understanding how social identity concerns frame the outcome of
      perspective taking is crucial to its effective employment in intergroup-relations
      programs.

PMID- 22851439
TI  - Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian
      patients.
AB  - BACKGROUND: Warfarin remains a difficult drug to use due to the large variability
      in dose response. Clear understanding of the accuracy of warfarin pharmacogenetic
      dosing methods might lead to appropriate control of anticoagulation. OBJECTIVE:
      This study aims to evaluate the accuracy of warfarin dosing table and two
      pharmacogenetic algorithms, namely the algorithms of Gage et al. (Clin Pharmacol
      Ther 84:326-331, 2008), and the International Warfarin Pharmacogenetics
      Consortium algorithm (IWPC) in a real Egyptian clinical setting. Additionally,
      three non-pharmacogenetic dosing methods (the Gage, IWPC clinical algorithms and
      the empiric 5 mg/day dosing) were evaluated. SETTING: Sixty-three Egyptian
      patients on a stable therapeutic warfarin dose were included. Patients were
      recruited from the outpatient clinic of the critical care medicine department.
      METHODS: CYP2C9 and VKORC1 polymorphisms were genotyped by real time PCR system.
      Predicted doses by all dosing methods were calculated and compared with the
      actual therapeutic warfarin doses. RESULTS: The Gage algorithm (adjusted R(2) =
      0.421, and mean absolute error (MAE) = 3.3), and IWPC algorithm (adjusted R(2) =
      0.419, MAE = 3.2) produced better accuracy than did the warfarin dosing table
      (adjusted R(2) = 0.246, MAE = 3.5), the two clinical algorithms (R(2) = 0.24, MAE
      = 3.7) and the fixed dose approach (MAE = 3.9). However, all dosing models
      produced comparable clinical accuracy with respect to proportion of patients
      within 1 mg/day of actual dose (ideal dose). Non-pharmacogenetic methods severely
      over-predicted dose (defined as >=2 mg/day more than actual dose) compared to the
      three pharmacogenetic models. In comparison to non-pharmacogenetic methods, the
      three pharmacogenetic models performed better regarding the low dose group in
      terms of percentage of patients within ideal dose. In the high dose group, none
      of the dosing models predicted warfarin doses within ideal dose. CONCLUSION: Our
      study showed that genotype-based dosing improved prediction of warfarin
      therapeutic dose beyond that available with the fixed-dose approach or the
      clinical algorithms, especially in the low-dose group. However, the two
      pharmacogenetic algorithms were the most accurate.

PMID- 22851442
TI  - Independence of data-driven and conceptually driven priming: the case of person
      recognition.
AB  - A central tenet of current memory theories is the independence of data-driven and
      conceptually driven priming. Although these types of repetition priming have
      different functional properties, it has remained unclear whether they are
      independent and additive or interact with each other. Therefore, we orthogonally
      combined these priming types in two experiments requiring occupation judgments
      for celebrities, represented by their faces or names. In both experiments, the
      sum of the effects of separate data-driven priming and conceptually driven
      priming equaled the effect of the combination of these priming types. These
      findings demonstrate for the first time the independence of data-driven and
      conceptually driven priming and so confirm a central tenet of current memory
      theories. This independence may thus be an important element for the development
      of future overarching memory theories.

PMID- 22851443
TI  - Young children are intrinsically motivated to see others helped.
AB  - Young children help other people, but it is not clear why. In the current study,
      we found that 2-year-old children's sympathetic arousal, as measured by relative
      changes in pupil dilation, is similar when they themselves help a person and when
      they see that person being helped by a third party (and sympathetic arousal in
      both cases is different from that when the person is not being helped at all).
      These results demonstrate that the intrinsic motivation for young children's
      helping behavior does not require that they perform the behavior themselves and
      thus "get credit" for it, but rather requires only that the other person be
      helped. Thus, from an early age, humans seem to have genuine concern for the
      welfare of others.

PMID- 22851444
TI  - Skeletal age assessment in children using an open compact MRI system.
AB  - MRI may be a noninvasive and alternative tool for skeletal age assessment in
      children, although few studies have reported on this topic. In this article,
      skeletal age was assessed over a wide range of ages using an open, compact MRI
      optimized for the imaging of a child's hand and wrist, and its validity was
      evaluated. MR images and their three-dimensional segmentation visualized detailed
      skeletal features of each bone in the hand and wrist. Skeletal age was then
      independently scored from the MR images by two raters, according to the Tanner
      Whitehouse Japan system. The skeletal age assessed by MR rating demonstrated a
      strong positive correlation with chronological age. The intrarater and inter
      rater reproducibilities were significantly high. These results demonstrate the
      validity and reliability of skeletal age assessment using MRI.

PMID- 22851445
TI  - Basic biology of GAPDH.
AB  - The GAPDH gene is highly conserved with a promoter that contains several types of
      regulatory elements, perhaps even in a distal intron. Curiously, the
      transcription start site shows some ambiguity and there are codon-sharing exons
      at alternate exon junctions. While there is only one functional gene for GAPDH in
      humans, the genome is littered with pseudogenes, representing a trove of
      researchable content. Tissue-specific expression speaks to the glycolytic
      function of GAPDH; thus, it's not surprising to see expression increased in
      cancer cells. Modulation of protein levels becomes an opportunity for
      intervention. The abundance of GAPDH in the cell provides the rationale (albeit,
      tenuous) for its use as a loading control. The single paralogous GAPDHS, which is
      the spermatogenic form of the protein, provides a curious study in cell-type
      specificity and perhaps intervention (i.e. contraception). And it is no wonder
      that great biochemists were kept busy for decades unveiling the nuances of GAPDH
      enzymology. While the active site of the enzyme is well-characterized and the
      catalytic mechanism is well-described, the role of inter-subunit interactions in
      catalysis still offers some mysteries, particularly with regards to other
      emerging enzymatic properties. The GAPDH protein exhibits an intrinsic asymmetry
      of the subunits, which also may speak to its functional diversity.

PMID- 22851446
TI  - GAPDH and intermediary metabolism.
AB  - GAPDH plays a major enzymatic role in the intermediary metabolism of human
      tissues. In fact, the cells of all organisms require the catalytic capability of
      GAPDH in order to maintain adequate glycolytic flux. Even the primitive archaea
      rely on GAPDH in a pivotal step in the Entner-Doudoroff pathway, which is a
      series of reactions that resembles glycolysis. GAPDH catalyzes the sixth reaction
      of glycolysis in eukaryotic cells and represents a regulatory hurdle in anaerobic
      glycolysis. The triose substrate of GAPDH is actually a product of several
      important metabolic pathways: stage one of glycolysis, fructose catabolism,
      pentose phosphate pathway and glycerol metabolism. The GAPDH reaction is
      reversible, hence, necessary for hepatic gluconeogenesis. The chapter discusses
      GAPDH as being a metabolic 'switching station', diverting carbon flow
      appropriately. There is discussion regarding the experimental analysis of GAPDH's
      enzymatic function, particularly in the use of inhibitors. The GAPDH gene is
      portrayed in the context of the enzyme's role in metabolism. The observed
      intolerance to genetic mutation suggests that the genetic changes (i.e. those
      seen across species) may provide a treasure of information regarding the limits
      of genetic variability that can be tolerated and still allow for the protein to
      conduct essential glycolytic - as well as non-glycolytic - functions.

PMID- 22851447
TI  - Compartmentation of GAPDH.
AB  - The concept of the cytosol as a space that contains discrete zones of metabolites
      is discussed relative to the contribution of GAPDH. GAPDH is directed to very
      specific cell compartments. This chapter describes the utilization of GAPDH's
      enzymatic function for focal demands (i.e. ATP/ADP and NAD(+)/NADH), and offers a
      speculative role for GAPDH as perhaps moderating local concentrations of
      inorganic phosphate and hydrogen ions (i.e. co-substrate and co-product of the
      glycolytic reaction, respectively). Where known, the structural features of the
      binding between GAPDH and the compartment components are discussed. The nuances,
      which are associated with the intracellular distribution of GAPDH, appear to be
      specific to the cell-type, particularly with regards to the various plasma
      membrane proteins to which GAPDH binds. The chapter includes discussion on the
      curious observation of GAPDH being localized to the external surface of the
      plasma membrane in a human cell type. The default perspective has been that GAPDH
      localization is synonymous with compartmentation of glycolytic energy. The
      chapter discusses GAPDH translocation to the nucleus and to non-nuclear cellular
      structures, emphasizing its glycolytic function. Nevertheless, it is becoming
      clear that alternate functions of GAPDH play a role in compartmentation,
      particularly in the translocation to the nucleus.

PMID- 22851448
TI  - Functional diversity.
AB  - There is increasing evidence to support a gene economy model that is fully based
      on the principles of evolution in which a limited number of proteins does not
      necessarily reflect a finite number of biochemical processes. The concept of
      'gene sharing' proposes that a single protein can have alternate functions that
      are typically attributed to other proteins. GAPDH appears to play this role quite
      well in that it exhibits more than one function. GAPDH represents the prototype
      for this new paradigm of protein multi-functionality. The chapter discusses the
      diverse functions of GAPDH among three broad categories: cell structure, gene
      expression and signal transduction. Protein function is curiously re-specified
      given the cell's unique needs. GAPDH provides the cell with the means of linking
      metabolic activity to various cellular processes. While interpretations may often
      lead to GAPDH's role in meeting focal energy demands, this chapter discusses
      several other very distinct GAPDH functions (i.e. membrane fusogenic properties)
      that are quite different from its ability to catalyze oxidative phosphorylation
      of the triose, glyceraldehyde 3-phosphate. It is suggested that a single protein
      participates in multiple processes in the structural organization of the cell,
      controls the transmission of genetic information (i.e. GAPDH's involvement may
      not be finite) and mediates intracellular signaling.

PMID- 22851449
TI  - GAPDH, as a virulence factor.
AB  - Pathogens, such as bacteria, viruses, protozoa and fungi, generate molecules that
      provide them with a selective advantage, often at the expense of the host. These
      molecules, or virulence factors, enable pathogens to colonize the host through
      several mechanisms. Some molecules offer the pathogen an advantage through better
      adhesion to host tissues, or superior invasive capability. Some allow the
      pathogen to evade or suppress the host's immune system. Some molecules enable
      intracellular parasites to disable cytoprotective mechansims, by re-directing the
      host phagocytic vesicles. Many of these molecules are proteins that are exported
      to the cell's surface or are secreted. As unlikely as it seems, GAPDH appears to
      play a role as a virulence factor in a number of pathogenic organisms by the
      mechanisms just described. This highly conserved protein is found on the outer
      surface or as a secretory product of these organisms. The process by which
      pathogenic GAPDH, which has >40 % sequence identity to human GAPDH, is exported
      and attached to the outer surface of cells remains unknown. This chapter also
      presents a previously unpublished proposed docking sequence on GAPDH. There is
      also discussion of the potential of using the antigenic properties of pathogenic
      GAPDH for medical as well as for veterinary purposes.

PMID- 22851450
TI  - Target for diverse chemical modifications.
AB  - The chapter begins with an historical perspective of GAPDH isozymes that is
      juxtaposed to the fact that there is only one somatic functional gene in humans
      that is virtually identical among the mammalian species. Over the many years of
      GAPDH research, dozens of labs have reported the existence of multiple forms of
      GAPDH, which mostly vary as a function of charge with an occasional report of
      truncated forms. These observations are in part due to GAPDH being a substrate
      for many enzymatically-controlled post-translational modifications. While target
      residues have been identified and predictive algorithms have implicated certain
      residues, this area of research appears to be in its infancy regarding GAPDH.
      Equally fascinating, the uniquely susceptible nature of GAPDH to non-enzymatic
      reactions, that typically are associated with cell stress, such as oxidation and
      nitration, is also discussed. Two metabolic gases, nitric oxide and hydrogen
      sulfide, which are enzymatically produced, appear to exert their signaling
      properties through non-enzymatic reaction with GAPDH. Models of cellular decline
      are also proposed, including the compelling hypothesis that states cell
      compromise occurs by the physically blocking the function of chaperonins (i.e.
      dual-ring multiple-subunit molecular chaperones) by the attachment of misfolded
      GAPDH.

PMID- 22851451
TI  - Dynamic oligomeric properties.
AB  - This chapter provides a foundation for further research into the relationship
      between dynamic oligomeric properties and functional diversity. The structural
      basis that underlies the conformational sub-states of the GAPDH oligomer is
      discussed. The issue of protein stability is given a thorough analysis, since it
      is well-established that the primary strategy for protein oligomerization is to
      stabilize conformation. Several factors that affect oligomerization are
      described, including chemical modification by synthetic reagents. The effects of
      native substrates and coenzymes are also discussed. The curious feature of
      chloride ions having a de-stabilizing effect on native GAPDH structure is
      described. Additionally, the role of adenine dinucleotides in tetramer-dimer
      equilibrium dynamics is suggested to be a major part of the physiological
      regulation of GAPDH structure and function. This chapter also contends that a
      vast amount of useful information can come from comparative analyses of diverse
      species, particularly regarding protein stability and subunit-subunit
      interaction. Lastly, the concept of domain exchange is introduced as a means of
      understanding the stabilization of dynamic oligomers, suggesting that inter
      subunit contacts may also be a way of masking docking sites to other proteins.

PMID- 22851452
TI  - Multiple binding partners.
AB  - GAPDH interacts with a plethora of diverse cellular proteins. The network of
      interacting partners, or interactome, is presented for GAPDH with the interacting
      molecules grouped into specific functional and structural categories. By
      organizing the binding partners in this way, certain common structural features
      are beginning to surface, such as acidic dipeptide sequences that are found in
      several of these binding proteins. Additionally, the consensus sequences for
      target polynucleotides are being brought to light. The categories, which are
      presented according to function, offer an opportunity for research into the
      corresponding structural correlates to these interactions. Recent discoveries of
      interacting proteins have revealed novel relationships that are generating
      emerging mechanisms. Proteins that are associated with age-related
      neurodegenerative diseases appear to be particularly prone to binding GAPDH,
      suggesting that GAPDH may be playing a role in these diseases. Neurodegenerative
      diseases that are discussed are the conformational diseases of aging, suggesting
      that GAPDH may be a global sensor for cellular conformational stress. In addition
      to GAPDH's oxidoreductase activity, several other enzymatic functions have been
      discovered, including peroxidase, nitrosylase, mono-ADP-ribosylase and kinase
      activities.

PMID- 22851453
TI  - GAPDH in anesthesia.
AB  - Thus far, two independent laboratories have shown that inhaled anesthetics
      directly affect GAPDH structure and function. Additionally, it has been
      demonstrated that GAPDH normally regulates the function of GABA (type A)
      receptor. In light of these literature observations and some less direct
      findings, there is a discussion on the putative role of GAPDH in anesthesia. The
      binding site of inhaled anesthetics is described from literature reports on model
      proteins, such as human serum albumin and apoferritin. In addition to the
      expected hydrophobic residues that occupy the binding cavity, there are
      hydrophilic residues at or in very close proximity to the site of anesthetic
      binding. A putative binding site in the bacterial analog of the human GABA (type
      A) receptor is also described. Additionally, GAPDH may also play a role in
      anesthetic preconditioning, a phenomenon that confers protection of cells and
      tissues to future challenges by noxious stimuli. The central thesis regarding
      this paradigm is that inhaled anesthetics evoke an intra-molecular protein
      dehydration that is recognized by the cell, eliciting a very specific burst of
      chaperone gene expression. The chaperones that are implicated are associated with
      conferring protection against dehydration-induced protein aggregation.

PMID- 22851454
TI  - MoS2 nanosheets for top-gate nonvolatile memory transistor channel.

PMID- 22851455
TI  - Registration of prostate histology images to ex vivo MR images via strand-shaped
      fiducials.
AB  - PURPOSE: To present and evaluate a method for registration of whole-mount
      prostate digital histology images to ex vivo magnetic resonance (MR) images.
      MATERIALS AND METHODS: Nine radical prostatectomy specimens were marked with 10
      strand-shaped fiducial markers per specimen, imaged with T1- and T2-weighted 3T
      MRI protocols, sliced at 4.4-mm intervals, processed for whole-mount histology,
      and the resulting histological sections (3-5 per specimen, 34 in total) were
      digitized. The correspondence between fiducial markers on histology and MR images
      yielded an initial registration, which was refined by a local optimization
      technique, yielding the least-squares best-fit affine transformation between
      corresponding fiducial points on histology and MR images. Accuracy was quantified
      as the postregistration 3D distance between landmarks (3-7 per section, 184 in
      total) on histology and MR images, and compared to a previous state-of-the-art
      registration method. RESULTS: The proposed method and previous method had mean
      (SD) target registration errors of 0.71 (0.38) mm and 1.21 (0.74) mm,
      respectively, requiring 3 and 11 hours of processing time, respectively.
      CONCLUSION: The proposed method registers digital histology to prostate MR
      images, yielding 70% reduced processing time and mean accuracy sufficient to
      achieve 85% overlap on histology and ex vivo MR images for a 0.2 cc spherical
      tumor.

PMID- 22851456
TI  - Misuse of the p value for baseline characteristics.

PMID- 22851457
TI  - Glutamate gene polymorphisms predict brain volumes in multiple sclerosis.
AB  - BACKGROUND: Several genetic markers have been associated with multiple sclerosis
      (MS) susceptibility; however, uncovering the genetic aetiology of the complex
      phenotypic expression of MS has been more difficult so far. The most common
      approach in imaging genetics is based on mass-univariate linear modelling (MULM),
      which faces several limitations. OBJECTIVE: Here we apply a novel multivariate
      statistical model, sparse reduced-rank regression (sRRR), to identify possible
      associations of glutamate related single nucleotide polymorphisms (SNPs) and
      multiple MRI-derived phenotypes in MS. METHODS: Seven phenotypes related to brain
      and lesion volumes for a total number of 326 relapsing-remitting and secondary
      progressive MS patients and a total of 3809 glutamate related and control SNPs
      were analysed with sRRR, which resulted in a ranking of SNPs in decreasing order
      of importance ('selection probability'). Lasso regression and MULM were used as
      comparative statistical techniques to assess consistency of the most important
      associations over different statistical models. RESULTS: Five SNPs within the
      NMDA-receptor-2A-subunit (GRIN2A) domain were identified by sRRR in association
      with normalized brain volume (NBV), normalized grey matter volume and normalized
      white matter volume (NMWM). The association between GRIN2A and both NBV and NWMV
      was confirmed in MULM and Lasso analysis. CONCLUSIONS: Using a novel,
      multivariate regression model confirmed by two other statistical approaches we
      show associations between GRIN2A SNPs and phenotypic variation in NBV and NWMV in
      this first exploratory study. Replications in independent datasets are now
      necessary to validate these findings.

PMID- 22851458
TI  - [What kind of school do children need?].
AB  - At every age abilities mature and are internalized through corresponding
      experience. Every child wants to develop and learn, but at his own pace. In this
      process the child is not only active, but also selective, that is, it seeks
      experiences that correspond to its stage of development. The task of the school
      consists of making it possible for the child to gain learning experience that
      suits its stage of development in the respective areas of competence. Not only
      does the cognitive competence of children vary, but they also have differing
      needs as to emotional security and social experience. If it is possible to create
      an optimal balance in each of the three areas, learning experience, emotional
      security and socialization, between the needs and the individual development of
      the child and its environment, then the child can develop in the best possible
      way.

PMID- 22851459
TI  - [The child with a chronic disease at school-age].
AB  - Advances in medical treatment have led to an increase survival of children
      suffering from severe diseases. Often times, these children will develop a
      chronic disorder thereafter. The care of these children and families is a
      challenging task for primary care providers. Children with chronic disorders may
      manifest medical complications, but may also face psychosocial and
      neurodevelopmental sequelae. Psychological maladjustment may occur independent of
      the underlying medical condition and quality of life can be impaired.
      Interestingly, quality of life is better if rated by the children themselves than
      if judged by their parents. Obviously, children with a chronic condition of the
      central nervous system have a high prevalence of neurodevelopmental problems.
      However, neurodevelopmental problems may also occur frequently in children at
      risk for developmental sequelae. Among those are children born before 32. weeks
      of gestation, those after perinatal asphyxia and children with a severe
      congenital heart defect. The prevalence of these three conditions is equally high
      at around 1 in 100 newborns. All three groups may face mild neurodevelopmental
      problems, which typically present at school-age. Problems may constitute of motor
      and intellectual difficulties and specific deficits in visuomotor and executive
      functions and often occur in combination. It is therefore of outmost importance
      that aside from regular specialized neurodevelopmental follow-up visits, these
      children are being followed closely by their primary care provider to early
      assess psychosocial and neurodevelopmental difficulties. These need to be
      evaluated and treated in association with other health care specialists.

PMID- 22851460
TI  - [The clumsy child].
AB  - This article describes the motor development of normal healthy children from
      school-age through adolescence and summarizes the recently published
      interdisciplinary clinical practice guidelines for the definition, origin,
      diagnosis, assessment and intervention of developmental coordination disorder
      (DCD).

PMID- 22851461
TI  - [The school child with ADHD].
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most frequent
      psychiatric disorders at school age. The core symptoms of hyperactivity,
      impulsivity and inattention emerge before the age of seven and are associated
      with severe impairment of the child's everyday functioning (family, school,
      leisure time). Seventy percent of the affected children show at least one
      comorbid psychiatric condition or learning disorder/academic impairment. ADHD is
      one of the most widely investigated disorders in child and adolescent psychiatry.
      A multitude of imaging (fMRI) and genetic studies comparing children with ADHD
      and typically developing children have provided clear evidence for the
      neurobiological foundation of ADHD. Nevertheless, environmental, familial and
      academic factors play an important role with regard to the persistence and
      severity of the disorder. Treatment should be preferentially multimodal, with
      interventions targeting the child, the parents, and, if possible, the teacher.
      Society with its specific requirements and constraints, and also school, are not
      well adjusted for children that are different, hyperactive and easily distracted.
      However, many of these children also have resources. When fascinated by a task,
      they may show persistence and commitment.

PMID- 22851462
TI  - [A case report on mobbing in a school child].
AB  - Forty percent of the work of a paediatrician in private practice consists of
      counselling parents and children. There is a danger that behavioural symptoms are
      not taken seriously and brushed away with simple advices. This case vignette
      demonstrates that difficult and complex symptoms can be solved by using a concept
      oriented approach.

PMID- 22851463
TI  - [The child presenting with arthralgia or arthritis - what do we need to
      consider?].
AB  - Musculoskeletal symptoms in children are among the most frequent presenting
      symptoms. Besides traumatic etiology - which accounts for most of the symptoms-
      more than 100 differential diagnoses need to be considered in the pediatric
      patients. Therefore children with limp pain or gait abnormalities always require
      thorough assessment for early exclusion of potentially threatening diseases e.g.
      leukemia, chronic metabolic or inflammatory diseases. Pediatric patients with
      arthralgia or arthritis therefore represent a population of risk which should
      always require referral to the experienced pediatrician whenever the diagnosis or
      condition of the child remains uncertain.

PMID- 22851464
TI  - [Physical activity and obesity in school-age].
AB  - Physical activity and obesity are two of the most used health expressions over
      the last years ranging from the lay press to the highest ranked scientific
      journals. Both reach their readers, as everybody is either affected him/herself
      or knows a person which has to be treated - or has to cover an explosive
      scientific topic and search for solutions to solve this worldwide problem of
      physical inactivity and obesity. It is obvious that we don't have the solution
      yet and that it will take many decades to normalize our built up construct of a
      motorized, extensive energy overload - if this is possible at all. Importantly,
      one has to acknowledge that mild overweight does not harm much, but if the
      muscles of the human body are not used, more disease and a reduced life
      expectancy occur. This is evident for the adult population, but this relation
      seems plausible for children as well. In this article, we will cover physical
      activity and overweight in the school child including diagnostic criteria, their
      relevance for health and describe practical approaches that may help to make of
      each school child an active and "normal weight" human being.

PMID- 22851465
TI  - [What you need to know about eating and drinking behavior in school-aged
      children].
AB  - "Eating and drinking" are key elements in and for the life of our children. They
      supply the child with sufficient energy and essential nutrients, they constitute
      the basis for an optimal growth and they initiate a good life style with
      sufficient physical activity, pleasure and other sensory inputs. This article
      provides important information on the optimal combination of food groups and
      presents recommendations regarding daily routine of children and families using
      the food pyramid and the nutrition disc of the Swiss society of nutrition. A
      short discussion covers the subjects of problematic eating habits (over,
      underweight), allergies as well as pseudoallergies and lactose intolerance.

PMID- 22851466
TI  - [Media use with developmental benefits].
AB  - For children of school age television is still the dominant medium. TV
      consumption isn't only limited on the TV set, but also happens on the computer
      with internet access and mobile devices. Computer games take a high priority for
      boys. For girls reading is still an important experience space. Parents influence
      the media use of their children by their role model, and the rates for shared non
      media experiences. Neighborhoods which aren't child-friendly can cause children's
      withdraw into home media spaces. Restrictions and controls are less important
      than the conversations that are conducted around media interests of the child and
      parents attention to early signs of problematic media use. Potentially irritating
      media content for children (such as violence or sex) can have strong effects when
      there's no open debate taking place in the family around these issues. Today's
      media diversity leads to parallel surfing and multi-tasking. In order that this
      doesn't influence children's cognitive development and learning negatively a
      culture of regular restriction to one activity, to which they devote their full
      attention, is required.

PMID- 22851467
TI  - Understanding the side effects of glucocorticoid therapy: shining a light on a
      drug everyone thinks they know.
AB  - Glucocorticoids are one of the most frequently prescribed therapies in
      rheumatology, a reflection of their effectiveness as a powerful anti-inflammatory
      drug. Glucocorticoids are also, however, associated with a wide range of adverse
      events, particularly at higher doses. To make appropriate decisions, doctors and
      patients need to weigh these benefits against the potential harms. This article
      describes the many uncertainties which make informed prescribing difficult. We
      lack knowledge, for example, on the magnitude of risk, the relationship to dose
      and duration, and what happens to risk on stopping therapy. Beyond safety, we
      describe how patients may lack understanding of the nature of the benefits and
      harms, and how to incorporate value judgements which are crucial to the decision
      making process. We conclude by exploring how future research might fill these
      knowledge gaps to enable a better informed decision process.

PMID- 22851468
TI  - Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in
      patients with primary Sjogren's syndrome: data from a placebo-controlled clinical
      trial.

PMID- 22851470
TI  - The intrinsic mechanical properties of rubrene single crystals.

PMID- 22851471
TI  - Translational genomics is not a spectator sport: a call to action.

PMID- 22851472
TI  - SVM-based generalized multifactor dimensionality reduction approaches for
      detecting gene-gene interactions in family studies.
AB  - Gene-gene interaction plays an important role in the etiology of complex
      diseases, which may exist without a genetic main effect. Most current statistical
      approaches, however, focus on assessing an interaction effect in the presence of
      the gene's main effects. It would be very helpful to develop methods that can
      detect not only the gene's main effects but also gene-gene interaction effects
      regardless of the existence of the gene's main effects while adjusting for
      confounding factors. In addition, when a disease variant is rare or when the
      sample size is quite limited, the statistical asymptotic properties are not
      applicable; therefore, approaches based on a reasonable and applicable
      computational framework would be practical and frequently applied. In this study,
      we have developed an extended support vector machine (SVM) method and an SVM
      based pedigree-based generalized multifactor dimensionality reduction (PGMDR)
      method to study interactions in the presence or absence of main effects of genes
      with an adjustment for covariates using limited samples of families. A new test
      statistic is proposed for classifying the affected and the unaffected in the SVM
      based PGMDR approach to improve performance in detecting gene-gene interactions.
      Simulation studies under various scenarios have been performed to compare the
      performances of the proposed and the original methods. The proposed and original
      approaches have been applied to a real data example for illustration and
      comparison. Both the simulation and real data studies show that the proposed SVM
      and SVM-based PGMDR methods have great prediction accuracies, consistencies, and
      power in detecting gene-gene interactions.

PMID- 22851473
TI  - Bootstrap aggregating of alternating decision trees to detect sets of SNPs that
      associate with disease.
AB  - Complex genetic disorders are a result of a combination of genetic and nongenetic
      factors, all potentially interacting. Machine learning methods hold the potential
      to identify multilocus and environmental associations thought to drive complex
      genetic traits. Decision trees, a popular machine learning technique, offer a
      computationally low complexity algorithm capable of detecting associated sets of
      single nucleotide polymorphisms (SNPs) of arbitrary size, including modern genome
      wide SNP scans. However, interpretation of the importance of an individual SNP
      within these trees can present challenges. We present a new decision tree
      algorithm denoted as Bagged Alternating Decision Trees (BADTrees) that is based
      on identifying common structural elements in a bootstrapped set of Alternating
      Decision Trees (ADTrees). The algorithm is order nk(2), where n is the number of
      SNPs considered and k is the number of SNPs in the tree constructed. Our
      simulation study suggests that BADTrees have higher power and lower type I error
      rates than ADTrees alone and comparable power with lower type I error rates
      compared to logistic regression. We illustrate the application of these data
      using simulated data as well as from the Lupus Large Association Study 1 (7,822
      SNPs in 3,548 individuals). Our results suggest that BADTrees hold promise as a
      low computational order algorithm for detecting complex combinations of SNP and
      environmental factors associated with disease.

PMID- 22851476
TI  - Myosin light chain isoforms retain their species-specific electrophoretic
      mobility after processing, which enables differentiation between six species: 2DE
      analysis of minced meat and meat products made from beef, pork and poultry.
AB  - Investigation of protein changes as well as authentication of meat is
      particularly difficult in processed meat products due to their different
      composition, complexity and very often inhomogeneity. The aim of this study was
      to check if the inter-species differences in the expression of myosin light chain
      (MLC) isoforms observed in raw meat were retained in meat products. MLCs from
      mixtures of minced meat (16 variants), frankfurters and sausages (15 products)
      made from cattle, pig, chicken, turkey, duck and goose were analysed by 2DE.
      Species-specific patterns of MLC isoforms were observed in all the mixtures and
      processed meat products. Relatively small degradation was observed in the MLCs
      after processing. Image analysis enabled species identification of the meat in
      all samples when the content of meat of one species was not lower than 10%.
      However, it was impossible to differentiate between all the six species under
      investigation on the basis of individual isoform. It was possible when the
      combination of all the three isoforms (myosin light chain 1 fast, myosin light
      chain 2 fast and myosin light chain 3 fast) was analysed. The results evidenced
      that MLCs have potential to be used as markers in authentication of meat products
      made from the analysed six species.

PMID- 22851469
TI  - Joint European League Against Rheumatism and European Renal Association-European
      Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the
      management of adult and paediatric lupus nephritis.
AB  - OBJECTIVES: To develop recommendations for the management of adult and paediatric
      lupus nephritis (LN). METHODS: The available evidence was systematically reviewed
      using the PubMed database. A modified Delphi method was used to compile
      questions, elicit expert opinions and reach consensus. RESULTS: Immunosuppressive
      treatment should be guided by renal biopsy, and aiming for complete renal
      response (proteinuria <0.5 g/24 h with normal or near-normal renal function).
      Hydroxychloroquine is recommended for all patients with LN. Because of a more
      favourable efficacy/toxicity ratio, as initial treatment for patients with class
      III-IV(A) or (A/C) (+/-V) LN according to the International Society of
      Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA)
      or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids
      is recommended. In patients with adverse clinical or histological features, CY
      can be prescribed at higher doses, while azathioprine is an alternative for
      milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in
      combination with oral glucocorticoids is recommended as initial treatment. In
      patients improving after initial treatment, subsequent immunosuppression with MPA
      or azathioprine is recommended for at least 3 years; in such cases, initial
      treatment with MPA should be followed by MPA. For MPA or CY failures, switching
      to the other agent, or to rituximab, is the suggested course of action. In
      anticipation of pregnancy, patients should be switched to appropriate medications
      without reducing the intensity of treatment. There is no evidence to suggest that
      management of LN should differ in children versus adults. CONCLUSIONS:
      Recommendations for the management of LN were developed using an evidence-based
      approach followed by expert consensus.

PMID- 22851474
TI  - Genotype imputation of Metabochip SNPs using a study-specific reference panel of
      ~4,000 haplotypes in African Americans from the Women's Health Initiative.
AB  - Genetic imputation has become standard practice in modern genetic studies.
      However, several important issues have not been adequately addressed including
      the utility of study-specific reference, performance in admixed populations, and
      quality for less common (minor allele frequency [MAF] 0.005-0.05) and rare (MAF <
      0.005) variants. These issues only recently became addressable with genome-wide
      association studies (GWAS) follow-up studies using dense genotyping or sequencing
      in large samples of non-European individuals. In this work, we constructed a
      study-specific reference panel of 3,924 haplotypes using African Americans in the
      Women's Health Initiative (WHI) genotyped on both the Metabochip and the
      Affymetrix 6.0 GWAS platform. We used this reference panel to impute into 6,459
      WHI SNP Health Association Resource (SHARe) study subjects with only GWAS
      genotypes. Our analysis confirmed the imputation quality metric Rsq (estimated
      r(2) , specific to each SNP) as an effective post-imputation filter. We recommend
      different Rsq thresholds for different MAF categories such that the average
      (across SNPs) Rsq is above the desired dosage r(2)  (squared Pearson correlation
      between imputed and experimental genotypes). With a desired dosage r(2)  of 80%,
      99.9% (97.5%, 83.6%, 52.0%, 20.5%) of SNPs with MAF > 0.05 (0.03-0.05, 0.01-0.03,
      0.005-0.01, and 0.001-0.005) passed the post-imputation filter. The average
      dosage r(2)  for these SNPs is 94.7%, 92.1%, 89.0%, 83.1%, and 79.7%,
      respectively. These results suggest that for African Americans imputation of
      Metabochip SNPs from GWAS data, including low frequency SNPs with MAF 0.005-0.05,
      is feasible and worthwhile for power increase in downstream association analysis
      provided a sizable reference panel is available.

PMID- 22851477
TI  - Validation of the Community Assessment Psychic Experiences -42 (CAPE-42) in
      Spanish college students and patients with psychosis.
AB  - Psychotic-like experiences can be considered as a vulnerability marker for
      psychotic disorders. The psychometric assessment of the extended psychosis
      phenotype has advanced considerably in recent years, although it must continue to
      deepen the quality of self-reports available for its assessment in Spanish
      population. The main goal was to analyze the psychometric quality of the
      Community Assessment Psychic Experiences-42 (CAPE-42) in Spanish college students
      and patients with psychosis. The final sample was comprised of a total of 660
      students (M = 20.3 years, SD = 2.6) and 97 patients with psychosis (M = 35.4
      years, SD = 10.2). The goodness of fit indices resulting from the confirmatory
      factor analysis that tested the hypothesized three-dimensional model (Positive,
      Negative and Depressive) were not adequate. In contrast, the exploratory factor
      analysis yielded a three-dimensional solution. Internal consistency values for
      the three dimensions of the CAPE-42 ranged between 0.78 and 0.89 in the sample of
      students and between 0.84 and 0.93 in the patients with psychosis. The CAPE-42
      scores correlated statistically significant with delusions and trait anxiety and
      state. These results show further evidence of validity of the CAPE-42 scores in
      samples of the Spanish population and support its use as a tool for the
      assessment of the extended psychosis phenotype.

PMID- 22851478
TI  - Pain related factors in newly diagnosed Generalized Anxiety Disorder patients.
AB  - PURPOSE: To determine the prevalence and factors associated to painful physical
      symptoms (PPS), pain as presentation, and neuropathic pain in generalized anxiety
      disorder (GAD) at primary care setting. METHODS: Multicenter, cross-sectional,
      observational study conducted on 404 Spanish primary care centers with 2,232
      patients. Data was collected at once and included demographic data, main reason
      for visit, psychiatric and medical illnesses, healthcare resource utilization.
      Validated scales used for GAD diagnosis were the MINI interview and GAD-7 scale.
      Depression was measured with the Hospital Anxiety and Depression Scale, sleep
      disturbances with the MOS-Sleep Scale, and pain with the Brief Pain Inventory,
      short version. RESULTS: Most patients reported PPS (93.5%). The main associated
      factors of PPS were consultation for gastrointestinal disease (OR=3.9) or for
      depression (OR=2.2), and being women (OR=1.5). PPS were the reason for visiting
      in 72.4 % of the sample. The main associated factors of PPS as the reason for
      consultation were clinical discomfort due to anxiety (OR=2.0), being female
      (OR=1.6), comorbid social anxiety (OR=1.4), and high Body Mass Index (OR=1.04).
      Neuropathic pain was present in 59.4% of all patients. Patients with diabetes
      (OR=2.6), social anxiety (OR=1.6), and depression (OR=1,6) suffered more
      frequently from neuropathic pain. CONCLUSION: This is the first study to
      establish the associated factors of PPS, neuropathic pain and pain as main reason
      for visiting in primary care patients with newly diagnosed GAD. Better knowledge
      factors associated to GAD could help to reduce its underdiagnosis and
      undertreatment at the primary care level.

PMID- 22851479
TI  - Prevalence and risk factors of psychotic symptoms in cocaine-dependent patients.
AB  - OBJECTIVES: Cocaine consumption can induce transient psychotic symptoms expressed
      as paranoia or hallucinations. This work reviews that evidence and tries to
      obtain data regarding frequency of psychotic symptoms or cocaine induced
      psychosis (CIP), risks or associated factors. METHOD: Systematic review of
      studies found in PubMed database published until January 2011 where cocaine
      induced paranoia was present. RESULTS: Cocaine induced paranoia has a particular
      clinical presentation. It needs to be clearly identified due to its harmful
      consequences. The prevalence is between 12% in clinical studies and 100% in
      experimental studies. The following are considered potential risk factors: age of
      first use and length, amount of substance, route of administration, body mass
      index, genetic factors, personal vulnerability and comorbidity with AXIS I
      (psychosis, ADHD) and AXIS II disorders (antisocial personality disorder).
      CONCLUSIONS: It is needed to research with larger samples of cocaine users of
      different countries and contexts, in order to identify and detail what variables
      are closely related in the development of cocaine induced paranoia, so the
      population at risk can be treated earlier.

PMID- 22851480
TI  - The course of the schizophrenia and its impact on cognition: a review of
      literature.
AB  - There has been increasing interest about cognition in schizophrenia during recent
      years. The greater focus of the investigators has been focused greater interest
      on the relation of cognitive deterioration with positive and negative symptoms,
      and functionality. However very few studies, if any, have specifically focused on
      the course of cognition in schizophrenic patients throughout the years. Those who
      have attempted to answer this question have done so by comparing cross-sectional
      studies of patients at different stages of their disease. Only a minority have
      used a longitudinal methodology in their studies. This article reviews a total of
      31 cross-sectional and 43 longitudinal studies published in patients with a
      diagnosis of schizophrenia. The diversity of criteria and methods used
      significantly limits the conclusions that can be drawn. After a comprehensive
      review of the literature on this topic, the authors have come to the conclusion
      that there are two opposite trends: 1) Cognition in schizophrenia follows a
      progressive decline over the years of evolution of the disease (a conclusion
      predominant in studies with cross-sectional methodology) and 2) Cognition in
      schizophrenia remains stable once it appears during the first stages of the
      disease (a conclusion predominant in longitudinal studies). The authors conclude
      that the question about the likely decline of cognition in schizophrenia cannot
      be answered due to the lack of rigorous and thorough follow-up studies.

PMID- 22851481
TI  - Quality of life in depressed women over 40 years old.
AB  - OBJECTIVES: This study aims to determine quality of life and satisfaction in
      depressed Spanish women over 40 years old in the outpatient psychiatry setting.
      Secondarily, the association between several characteristics of depressed
      patients and quality of life was assessed. MATERIAL AND METHODS: Cross-sectional,
      descriptive study, carried out in the Spanish psychiatry setting in 2008. A total
      of 365 Spanish psychiatrists participated. 1069 patients older than 18 years old
      signed the informed consent. Depressive symptoms were assessed using the 17 Item
      Hamilton for Depression Rating Scale (HAM-D17). The Quality of Life Enjoyment and
      Satisfaction Questionnaire (Q-LES-Q) scale assessed the patient's satisfaction
      and life enjoyment. RESULTS: Were included a total of 942 patients with the
      following characteristics: mean age of 52.46 years, medical comorbidity in 62.9%,
      and a history of psychiatric disorders in 79.6%. HAM-D17 mean score of 21.39.
      According to the Q-LES-Q questionnaire, Global satisfaction mean score was of
      35.2%, the highest mean scores were achieved in the treatment satisfaction and
      the lowest mean scores in free time activities. The quality of life was
      influenced by the intensity of depressive symptoms and physical comorbidity.
      CONCLUSION: The study results show an impairment of quality of life in depressed
      women attending outpatient psychiatric centers. This decrease in the quality of
      life is associated with depressive symptoms and medical comorbidity.

PMID- 22851482
TI  - Vascular psychosis in the elderly: response to clozapine.
AB  - Cerebrovascular disease is a cause of late-onset psychosis in the elderly more
      frequent, accompanied or not, multi-infarct dementia. In many cases the patient
      has adequate preservation of cognitive functions or in any case, no criteria for
      dementia. In those that do, is in vascular dementia where psychotic symptoms are
      more frequent, occurring in over half cases, compared to one third of patients
      with Alzheimer disease. A case of a 92 year-old woman with no somatic background 
      except for a bilateral progressive hearing loss-, who debuted at this age with
      psychotic delusions structured injury and auditory hallucinations. The CT scan
      showed signs of cortico-subcortical atrophy. Neuropsychological examinations
      showed some cognitive impairment but no clinical criteria for dementia. Was
      refractory to first-line atypical antipsychotics, remitting symptoms after
      administration of low doses of clozapine. We discuss the clinical features of
      this psychosis, as well as its therapeutic approach.

PMID- 22851483
TI  - Stuttering treated with olanzapine: a case report.
AB  - INTRODUCTION: Spasmophemia, also called stuttering or stammering, is a speech
      disorder characterized by impairment of the rhythm of words whose classical
      symptoms are blocks and repetitions. METHODOLOGY: We describe the case of a male
      patient, his evolution and therapeutic strategies and review the current
      literature on the subject. RESULTS: A 33-year-old patient was referred to our
      Mental Health Unit by his family doctor due to "speech problems and difficulty
      expressing ideas. His symptoms had worsened in recent weeks, with increase in his
      state of anxiety." Standing out in the consultation to the doctor, the patient
      experienced multiple blocks in expressing words, using circumlocutions and
      monosyllabic repetitions that made it very difficult to conduct the interview.
      Anticipatory anxiety and occasional obsessions of repeated checking also stand
      out. After six weeks of treatment with olanzapine 5 mg/daily, the patient showed
      significant improvement both in the fluency and anticipatory anxiety with
      decreased repetitions, blocking, interjections and broken words. DISCUSSION:
      Spasmophemia has been associated with dopaminergic hyperactivity, so that studies
      have been conducted with atypical antipsychotics. Fundamentally, olanzapine and
      risperidone have revealed promising results. Furthermore, several studies have
      shown that these patients have higher rates of anxiety. That is why
      antidepressants and antianxiety drugs such as clomipramine, paroxetine,
      fluoxetine, citalopram, sertraline and alprazolam have been used. CONCLUSION:
      Treatment with olanzapine, 5HT-2 and D1/ D2 antagonist, significantly improved
      the clinical picture as Boyd et al. have described in their systematic review.

PMID- 22851484
TI  - Apropos of an Olfactory Reference Syndrome case.
AB  - Olfactory Reference Syndrome (ORS) is one of the varieties of the somatic type of
      the Delusional Disorder, and it is characterized by the mistaken statement of a
      patient who declares the issuance of a foul odor coming from his own body and
      that others may notice. In the upcoming edition of the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-V) it has been proposed to break off ORS as an
      independent pathology. From an illustrative case report, we review the relevant
      literature and discuss this proposal.

PMID- 22851485
TI  - Shear bond strength of repairs in porcelain conditioned with laser.
AB  - The aim of this study was to evaluate the shear bond strength of repairs in
      porcelain conditioned with laser. Sixty porcelain discs were made and six groups
      were formed (n = 10): G1: conditioning with laser with potency 760 mW; G2:
      conditioning with laser with potency 760 mW and application of 37% phosphoric
      acid for 15 s; G3: conditioning with laser with potency 900 mW; G4: conditioning
      with laser with potency 900 mW and application of 37% phosphoric acid for 15 s;
      G5: application of 37% phosphoric acid for 15 s (group control) and G6:
      application of 10% hydrofluoric acid for 2 min. The composite resin was insert of
      incremental layers at the porcelain surface aided with a metal matrix, and
      photoactivation for 20 s each increment. The specimens were submitted to a
      thermal cycling by 1000 cycles of 30 s in each bath with temperature between 5
      and 55 degrees C. After the thermal cycling, specimens were submitted to the
      shear bond strength. The results were evaluated statistically through analysis of
      variance and Tukey's tests with 5% significance. The averages and standard
      deviation founded were: G1, 11.25 (+/-3.10); G2, 12.32 (+/-2.65); G3, 14.02 (+/
      2.38); G4, 13.44 (+/-2,07); G5, 9.91 (+/-2,18); G6, 12.74 (+/-2.67). The results
      showed that the femtosecond laser produced a shear bond strength of repairs in
      porcelain equal to the hydrofluoric acid and significantly superior to the use of
      phosphoric acid.

PMID- 22851486
TI  - Measurements of serum DHEA and DHEA sulphate levels improve the accuracy of the
      low-dose cosyntropin test in the diagnosis of central adrenal insufficiency.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of central adrenal insufficiency (AI)
      continues to be challenging, especially when it is partial. We have recently
      demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S)
      in establishing the diagnosis of central AI. The current investigation examined
      the added value of measuring serum dehydroepiandrosterone (DHEA) levels during
      low-dose (1 MUg) cosyntropin (LDC) stimulation in patients suspected to have
      central AI. METHODS: Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were
      measured preoperatively in 155 consecutive patients with pituitary masses and 63
      healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL
      HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients.
      Patients with NL-HPA underwent surgical removal of the sellar masses and received
      no glucocorticoids before, during, or after surgery. RESULTS: Baseline and LDC
      stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar
      to those of normal subjects. In contrast, patients with impaired HPA had lower
      baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were
      18 subjects in the latter group whose LDC-stimulated serum cortisol levels were
      greater than 18.0 MUg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA
      and DHEA-S levels were similar to the whole group of patients with impaired HPA
      function. The molar ratio of cortisol to DHEA did not change with LDC stimulation
      in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA
      had a higher baseline cortisol to DHEA molar ratio that increased further with
      LDC stimulation. CONCLUSIONS: Patients with impaired HPA function have a more
      severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum
      DHEA levels during LDC simulation provide additional valuable information that
      improves the diagnostic accuracy of LDC in patients suspected to have central AI.
      We recommend the inclusion of DHEA and DHEA-S measurements in the laboratory
      assessment of HPA function.

PMID- 22851487
TI  - Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic
      variability and patient-centered outcomes during insulin intensification in type
      1 and type 2 diabetes: a randomized, controlled, crossover trial.
AB  - CONTEXT: In patients with diabetes, intraday glucose variability might predict
      health outcomes independently from glycosylated hemoglobin (HbA1c). OBJECTIVE:
      Our objective was to evaluate patient satisfaction (PS), quality of life (QoL),
      glycemic control, and variability during insulin intensification to HbA1c below
      7.0%. PATIENTS, DESIGN, AND SETTING: Eighty-two type 1 and 306 insulin-treated
      type 2 diabetes patients (47% male; age 54+/-11 yr; HbA1c=7.8+/-0.7%)
      participated in this multicenter, randomized, crossover trial at 52 U.S. centers.
      INTERVENTIONS: Interventions included insulin glargine plus premeal glulisine
      (n=192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n=196) for 12 wk
      and crossed to the alternate arm for 12 wk. MAIN OUTCOME MEASURES: Main outcome
      measures included PS and QoL questionnaires, 3-d continuous glucose monitoring
      (CGM), and HbA1c every 4-8 wk. RESULTS: Mean+/-se HbA1c change was -0.39+/-0.09%
      for glargine-glulisine and -0.05+/-0.09% for premix (P<0.0001). The PS net
      benefit scale (0-100) improved from 51.1 to 60.5+/-1.2 for glargine-glulisine and
      worsened to 45.4+/-1.2 for premix (P<0.0001). The PS regimen acceptance scale was
      comparable (P=0.33). Overall QoL favored glargine-glulisine (P<0.001), as did
      perceived health (P<0.0001), symptom distress (P<0.0001), general health
      perceptions (P<0.01), and psychosocial (P<0.02). CGM daily glucose mean, daily
      glucose sd (glycemic variability), and percent time over 140 mg/dl were lower for
      glargine-glulisine by 13.1+/-2.7 mg/dl, 5.9+/-1.4 mg/dl, and 7.3+/-1.6%,
      respectively (all P<0.0001), with no difference in CGM percent time below 70
      mg/dl (P=0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM
      daily glucose, and glycemic variability were independent predictors of PS net
      benefit. CONCLUSIONS: Patient satisfaction was impacted more positively by
      improved QoL, reduced glucose variability, and better glycemic control with a
      basal-bolus regimen than negatively by the burden of additional injections,
      thereby facilitating insulin intensification and the ability to achieve HbA1c
      below 7.0%.

PMID- 22851488
TI  - Vasomotor symptoms and insulin resistance in the study of women's health across
      the nation.
AB  - CONTEXT: Emerging research suggests links between menopausal hot flashes and
      cardiovascular disease risk. The mechanisms underlying these associations are
      unclear, due to the incomplete understanding of the physiology of hot flashes.
      OBJECTIVE AND MAIN OUTCOME MEASURES: We examined the associations between hot
      flashes/night sweats and glucose and insulin resistance over 8 yr, controlling
      for cardiovascular risk factors and reproductive hormones. DESIGN, SETTING, AND
      PARTICIPANTS: Participants in the Study of Women's Health Across the Nation
      (SWAN) (n=3075), a longitudinal cohort study, were ages 42-52 yr at entry. Women
      completed questionnaires (hot flashes, night sweats: none, 1-5 d, >=6 d, past 2
      wk), physical measures (blood pressure, height, weight), and a fasting blood draw
      [serum glucose, insulin, estradiol (E2), FSH] annually for 8 yr. Hot
      flashes/night sweats were examined in relation to glucose and the homeostasis
      model assessment (HOMA) in mixed models, adjusting for demographics,
      cardiovascular risk factors, medications, and E2/FSH. RESULTS: Compared to no
      flashes, hot flashes were associated with a higher HOMAlog index [vs. none; hot
      flashes, 1-5 d: % difference (95% confidence interval), 2.37 (0.36-4.43), P=0.02;
      and >=6 d: 5.91 (3.17-8.72), P<0.0001] in multivariable models that included body
      mass index. Findings persisted adjusting for E2 or FSH, and were similar for
      night sweats. Findings were statistically significant, yet modest in magnitude,
      for the outcome glucose. CONCLUSIONS: Hot flashes were associated with a higher
      HOMA index, an estimate of insulin resistance, and to a lesser extent higher
      glucose. Metabolic factors may be relevant to understanding the link between hot
      flashes and cardiovascular disease risk.

PMID- 22851490
TI  - Agenesis of internal carotid artery and hypopituitarism: case report and review
      of literature.
AB  - CONTEXT: Agenesis of the internal carotid artery and hypoplasia of the internal
      carotid artery are rare congenital abnormalities, involving less than 0.01% of
      the general population. Congenital hypopituitarism is also a rare condition;
      thus, the association of the two entities is unlikely to be casual. We describe
      one pediatric case of agenesis of the internal carotid artery with
      hypopituitarism and review other known cases. EVIDENCE ACQUISITION AND SYNTHESIS:
      In this brief clinical case seminar, we summarize the current understanding of
      this association based on a MEDLINE search of all peer-reviewed publications
      (original articles and reviews) on this topic between 1980 and 2011. We found
      nine other cases, mainly diagnosed during childhood. Defects of pituitary
      function varied among cases; in four, midline anomalies were present. CONCLUSION:
      There are two theories that are not mutually exclusive to explain the association
      of congenital vascular malformation and pituitary hypoplasia with
      hypopituitarism: the first involves hemodynamic mechanisms, and the second,
      complex neural-crest differentiation and/or migration disorders. Whatever the
      real physiopathological mechanism responsible for this condition, it could be
      considered as a new clinical entity.

PMID- 22851489
TI  - Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue
      as a link between inflammation and extracellular matrix remodeling in obesity.
AB  - CONTEXT: Obesity is associated with an altered inflammatory and extracellular
      matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with
      proinflammatory effects. OBJECTIVE: We aimed to explore the expression levels of
      TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular
      fraction cells (SVFC) as well as its impact on inflammation and ECM regulation.
      We also analyzed the effect of the stimulation with TNF-alpha and
      lipopolysaccharide (LPS) on both SVFC and adipocytes. PATIENTS AND METHODS:
      Samples obtained from 75 subjects were used in the study. Expression levels of
      TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well
      as in both adipocytes and SVFC. In addition, Tnc expression was measured in two
      mice models of obesity. RESULTS: We show, for the first time, that VAT expression
      levels of TNC are increased in normoglycemic and type 2 diabetic obese patients
      (P<0.01) as well as in obese patients with nonalcoholic steatohepatitis (P<0.01).
      Furthermore, expression levels of Tnc in epididymal adipose tissue from two
      different mice models of obesity were significantly increased (P<0.01). TNC and
      TLR4 were mainly expressed by SVFC, and its expression was significantly enhanced
      (P<0.01) by TNF-alpha treatment. LPS treatment also increased mRNA levels of TNC.
      Moreover, the addition of exogenous TNC induced (P<0.05) TLR4 and CCL2 mRNA
      expression in human adipocyte cultures. CONCLUSIONS: These findings indicate that
      TNC is involved in the etiopathology of obesity via visceral adipose tissue
      inflammation representing a link with ECM remodeling.

PMID- 22851491
TI  - Potential role for retinoic acid in patients with Cushing's disease.
AB  - CONTEXT: Cushing's disease, i.e. cortisol excess due to an ACTH-secreting
      pituitary adenoma, is a rare disorder with considerable morbidity and mortality
      but no satisfactory medical treatment as yet. Experimental data have recently
      shown that retinoic acid restrains ACTH secretion by tumoral corticotropes.
      OBJECTIVE: Our objective was to evaluate the efficacy and safety profile of
      retinoic acid treatment in patients with Cushing's disease. DESIGN: This is a
      prospective, multicenter study. Seven patients with Cushing's disease (three men,
      four postmenopausal women) were started on 10 mg retinoic acid daily and dosage
      increased up to 80 mg daily for 6-12 months. ACTH, urinary free cortisol (UFC),
      and serum cortisol as well as clinical features of hypercortisolism and possible
      side effects of retinoic acid were evaluated at baseline, during retinoic acid
      administration, and after drug withdrawal. RESULTS: A marked decrease in UFC
      levels was observed in five patients; mean UFC levels on retinoic acid were 22
      73% of baseline values and normalization in UFC was achieved in three patients.
      Plasma ACTH decreased in the first month of treatment and then returned to
      pretreatment levels in responsive patients whereas no clear-cut pattern could be
      detected for serum cortisol. Blood pressure, glycemia, and signs of
      hypercortisolism, e.g. body weight and facial plethora, were ameliorated to a
      variable extent on treatment. Patients reported only mild adverse effects, e.g.
      xerophthalmia and arthralgias. CONCLUSIONS: Long-term treatment with retinoic
      acid proved beneficial and well tolerated in five of seven patients with
      Cushing's disease. This represents a novel, promising approach to medical
      treatment in Cushing's disease.

PMID- 22851492
TI  - Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic
      challenges.
AB  - CONTEXT: Central hypothyroidism (CH) is a particular hypothyroid condition due to
      an insufficient stimulation by TSH of an otherwise normal thyroid gland. This
      condition raises several challenges for clinicians; therefore, a review of the
      most relevant findings on CH epidemiology, pathogenesis, and clinical management
      has been performed. METHODOLOGY: The relevant papers were selected by a PubMed
      search using appropriate key words. MAIN FINDINGS: CH can be the consequence of
      various disorders affecting either the pituitary gland or the hypothalamus, but
      most frequently affecting both of them. CH is about 1000-fold rarer than primary
      hypothyroidism. Except for the neonatal CH due to biallelic TSHbeta mutations,
      the thyroid hormone defect is rarely as profound as can be observed in some
      primary forms. In contrast with primary hypothyroidism, CH is most frequently
      characterized by low/normal TSH levels, and adequate thyroid hormone replacement
      is associated with the suppression of residual TSH secretion. Thus, CH often
      represents a clinical challenge because physicians cannot rely on the systematic
      use of the "reflex TSH strategy." The clinical management of CH is further
      complicated by the frequent combination with other pituitary deficiencies and
      their substitution.

PMID- 22851493
TI  - Molecular cloning of soluble trehalase from Chironomus riparius larvae, its
      heterologous expression in Escherichia coli and bioinformatic analysis.
AB  - Trehalase is involved in the control of trehalose concentration, the main blood
      sugar in insects. Here, we describe the molecular cloning of the cDNA encoding
      for the soluble form of the trehalase from the midge larvae of Chironomus
      riparius, a well-known bioindicator of the quality of freshwater environments.
      Molecular cloning was achieved through multiple alignment of Diptera trehalase
      sequences, allowing the synthesis of internal homology-based primers; the
      complete open reading frame(ORF) was subsequently obtained through RACE-PCR(where
      RACE is rapid amplification of cDNA ends). The cDNA contained the 5' untranslated
      region (UTR), the 3' UTR including a poly(A) tail and the ORF of 1,725 bp
      consisting of 574 amino acid residues with a predicted molecular mass of 65,778
      Da. Recombinant trehalase was successfully expressed in Escherichia coli as a His
      tagged protein and purified on Ni-NTA affinity chromatography. Primary structure
      analysis showed a series of characteristic features shared by all insect
      trehalases, while three-dimensional structure prediction yielded the typical
      glucosidase fold, the two key residues involved in the catalytic mechanism being
      conserved. Production of recombinant insect trehalases opens the way to
      structural characterizations of the catalytic site, which might represent, among
      others, an element for reconsidering the enzyme as a target in pest insects'
      control.

PMID- 22851494
TI  - Has highly active antiretroviral therapy increased the time to seroreversion in
      HIV exposed but uninfected children?
AB  - BACKGROUND: Since the introduction of highly active antiretroviral therapy
      (HAART) for prevention of mother-to-child transmission of human immunodeficiency
      virus (HIV) in pregnancy in the United States, the time of seroreversion in
      infants born to HIV-infected mothers has not been documented. The objective of
      this study was to determine the timing of clearance of HIV antibodies and to
      identify any associated biological and clinical factors. METHODS: A retrospective
      analysis of infants who remained uninfected after perinatal HIV exposure was
      performed. Infant and maternal medical records from January 2000 to December 2007
      were reviewed and the time of seroreversion was estimated using methods for
      censored survival data. RESULTS: In total, 744 infants were included in the
      study, with prenatal data available for 551 mothers. The median age of
      seroreversion was 13.9 months, and 14% of infants remained seropositive after 18
      months, 4.3% after 21 months, and 1.2% after 24 months. Earlier age of
      seroreversion was associated with higher immunoglobulin G (IgG) levels at 3-7
      months of age (P = .0029) and a higher rate of IgG change over the next 6 months
      of life (P = .003). Infants born by vaginal delivery were more likely to
      serorevert at a younger age (P = .0052), and maternal exposure to protease
      inhibitors was associated with a later age of seroreversion (P = .026).
      CONCLUSIONS: Clearance of HIV antibodies in uninfected infants was found to occur
      at a later age than has been previously reported. Fourteen percent of the infants
      had persistence of HIV antibodies at or beyond 18 months of age.

PMID- 22851495
TI  - Using the associative imagery technique in qualitative health research: the
      experiences of homecare workers and consumers.
AB  - The associative imagery technique is a qualitative tool with which researchers
      use carefully selected photographs or images to trigger participants' responses
      to explain difficult behavioral and social concepts. In this article, we describe
      the development and implementation of the associative imagery method in focus
      groups to understand the complex relationships between homecare workers and their
      clients as part of a larger health and safety intervention project conducted by
      the National Institute for Occupational Safety and Health. A total of 116
      homecare workers and clients were recruited for the study. We found that
      participants used images mainly in two ways. First, the images served to remind
      participants of specific persons, events, and/or objects. Second, the images
      facilitated recollections and reflections that allowed participants to
      metaphorically describe their experiences, feelings, and emotions. Both usages of
      imagery generated comments that answered the research question in a more
      relevant, descriptive, and vivid way.

PMID- 22851496
TI  - Enrichment and detection of tyrosine-nitrated proteins.
AB  - Nitrotyrosine is a post-translationally modified amino acid with distinctly
      different properties than tyrosine or any other of the genetically encoded amino
      acids. Detecting proteins containing nitrotyrosine is the first step towards a
      better understanding of the role of nitrotyrosine in health and disease.
      Moreover, quantifying the extent of nitrotyrosine and determining its location in
      a protein forms the basis for a better understanding of the effect of tyrosine
      nitration on biological function. Described in this unit is a method to detect
      tyrosine-nitrated proteins in tissue sections and on western blots after creating
      a fluorescent complex between aminotyrosine, salicylaldehyde, and Al(3+). In
      addition, an approach is detailed for labeling aminotyrosine with biotin to
      enrich peptides from complex samples. Both methods require reduction of
      nitrotyrosine to aminotyrosine, which can be achieved with sodium dithionite or
      hemin plus dithiothreitol.

PMID- 22851497
TI  - Introduction to peptide synthesis.
AB  - A number of synthetic peptides are significant commercial or pharmaceutical
      products, ranging from the dipeptide sugar substitute aspartame to clinically
      used hormones such as oxytocin, adrenocorticotropic hormone, and calcitonin. This
      unit provides an overview of the field of synthetic peptides and proteins. It
      discusses selecting the solid support and common coupling reagents. Additional
      information is provided regarding common side reactions and synthesizing modified
      residues.

PMID- 22851498
TI  - Removal of detergents from proteins and peptides in a spin-column format.
AB  - To enable downstream analysis, it is critical to remove unbound detergents from
      protein and peptide samples. This unit describes the use of a high-performance
      resin that offers exceptional detergent removal for proteins and peptides. The
      easy-to-use spin format significantly improves results over the standard drip
      column and batch methodologies, with >95% removal of 1% to 5% detergents,
      including SDS, sodium deoxycholate, CHAPS, Triton X-100, Triton X-114, NP-40,
      Brij-35, octyl glucoside, octyl thioglucoside, and lauryl maltoside, with high
      recovery of proteins and peptides. Detergent removal efficiency is evaluated
      using colorimetric methods and mass spectrometry (MS). BSA tryptic peptides have
      been successfully analyzed by liquid chromatography-tandem mass spectrometry (LC
      MS/MS) and matrix-assisted laser desorption/ionization (MALDI)-MS for
      identification of protein, following detergent removal using the resin.
      Advantages of this method include speed (less than 15 min), efficient detergent
      removal, and high recovery of proteins and peptides.

PMID- 22851499
TI  - Isolation of monoclonal antibody charge variants by displacement chromatography.
AB  - This unit discusses the important parameters in designing and optimizing a
      separation of monoclonal antibody (mAb) charge variants from process streams by
      ion-exchange displacement chromatography, including sample preparation and
      selection of matrix, column, and appropriate buffer. A protocol is provided for
      determination of optimal column binding and displacement conditions, including
      cleaning and regeneration of the displacement columns.

PMID- 22851500
TI  - Exploring data from genetic association studies using Bayesian variable selection
      and the Dirichlet process: application to searching for gene * gene patterns.
AB  - We construct data exploration tools for recognizing important covariate patterns
      associated with a phenotype, with particular focus on searching for association
      with gene-gene patterns. To this end, we propose a new variable selection
      procedure that employs latent selection weights and compare it to an alternative
      formulation. The selection procedures are implemented in tandem with a Dirichlet
      process mixture model for the flexible clustering of genetic and epidemiological
      profiles. We illustrate our approach with the aid of simulated data and the
      analysis of a real data set from a genome-wide association study.

PMID- 22851501
TI  - beta-D-glucosyl conjugates of highly potent inhibitors of blood coagulation
      factor Xa bearing 2-chorothiophene as a P1 motif.
AB  - We synthesized a novel O-glucoside of the recently reported potent factor Xa
      (fXa) inhibitor 1, which bears a 5-chlorothien-2-yl moiety and 1
      isopropylpiperidine as fragments that bind the S1 and S4 enzyme pockets,
      respectively. A beta-D-glucosyl unit was conjugated through an ether-linked C3
      alkyl spacer to the central phenyl ring of 1. The synthesized beta-D-glucose
      based compound 16 achieved picomolar inhibitory potency against human fXa
      (K(i)=60 pM) and high selectivity over thrombin and other serine proteases. In
      addition to the chlorothienyl S1 binder, a large gain in DeltaG resulted from the
      addition of protonated 1-isopropylpiperidine (DeltaDeltaG=29.7-30.5 kJ mol(-1)),
      which should bind to the aromatic S4 pocket through efficient cation-pi and C
      H...pi interactions. Instead, the C3-alkyl-linked glucose fragment, which is
      likely directed toward the solvent outside the enzyme binding site, improves
      DeltaG by an average of 2.9-3.8 kJ mol(-1) . Compound 16 showed sub-micromolar in
      vitro anticoagulant activity, as assessed by prothrombin time (PT) and activated
      thromboplastin time (aPTT) clotting assays in pooled human plasma (PT(2) and
      aPTT(2) equal to 0.135 and 0.389 MUM, respectively). Although compound 16 was 1.4
      fold less active than parent compound 1 in the ex vivo anticoagulant assay in
      mice, it showed a significant (1.6-fold) prolongation of PT relative to controls
      (P<0.05) 60 min after oral dosing (75 mg kg(-1)).

PMID- 22851502
TI  - A novel electromechanical actuation mechanism of a carbon nanotube fiber.
AB  - A spun carbon nanotube fiber functions as a torsional actuator in almost all
      available environmental media such as air, water, organic solvents, and
      electrolyte solutions. The Ampere's Law among helically aligned carbon nanotubes
      explains the simultaneous occurrence of lengthwise contraction and rotary torsion
      upon applying a low current. The produced stress is over 100 times that of the
      strongest natural skeletal muscle with high reversibility and good stability. The
      use of torsional fibers for electric motors is demonstrated.

PMID- 22851503
TI  - Gene identification and enzymatic properties of a membrane-bound trehalase from
      the ovary of Rhodnius prolixus.
AB  - Trehalose represents the main hemolymph sugar in most insects and its metabolic
      availability is regulated by trehalase. In this study, trehalase activity
      associated with the reproductive system was investigated in the insect Rhodnius
      prolixus, a hematophagous hemipteran vector of Chagas' disease. A single-copy
      gene that encodes a membrane-bound trehalase (RpTre-2) was identified in the
      genome of R. prolixus. RpTre-2 deduced amino acid sequence is closely related to
      other insect membrane-bound trehalases. The expression of this gene was detected
      in all analyzed organs, including ovary, where total trehalase enzymatic activity
      was determined, and was highest at day 7 after blood meal. Ovary membranes showed
      a major trehalase specific activity, which confirmed the presence of a membrane
      bound trehalase in this insect. This trehalase activity seemed not to be
      regulated at transcriptional level, as the expression of RpTre-2 gene in the
      ovary did not change over the days after feeding. Similarly, ovarian follicles at
      different developmental stages did not show any variation in the transcription
      level of this gene. The RpTre-2 kinetic parameters were also investigated.
      Activity was highest at pH 5.5 and followed Michaelis-Menten kinetics, with an
      apparent K(m)  = 1.42 +/- 0.36 mM and Vmax = 167.90 +/- 12.91 nmol/mg protein/h.
      These data reveal the presence of a membrane-bound trehalase in R. prolixus that
      is active in ovary and probably takes part in the insect carbohydrate metabolism
      associated with the reproductive process.

PMID- 22851504
TI  - Macroscopic 3D nanographene with dynamically tunable bulk properties.

PMID- 22851505
TI  - Asymmetric Bronsted acid-catalyzed nazarov cyclization of acyclic alpha-alkoxy
      dienones.
AB  - A Bronsted acid-catalyzed asymmetric Nazarov cyclization of acyclic alpha-alkoxy
      dienones has been developed. The reaction offers access to chiral cyclopentenones
      in a highly enantioselective manner. The reaction is complementary to our
      previously reported Bronsted acid-catalyzed electrocyclization reactions, which
      provided differently substituted optically active cyclopentenones with a fused
      tetrahydropyrane ring in good yields and with excellent enantioselectivities.

PMID- 22851506
TI  - Combining family and twin data in association studies to estimate the
      noninherited maternal antigens effect.
AB  - It is hypothesized that certain alleles can have a protective effect not only
      when inherited by the offspring but also as noninherited maternal antigens
      (NIMA). To estimate the NIMA effect, large samples of families are needed. When
      large samples are not available, we propose a combined approach to estimate the
      NIMA effect from ascertained nuclear families and twin pairs. We develop a
      likelihood-based approach allowing for several ascertainment schemes, to
      accommodate for the outcome-dependent sampling scheme, and a family-specific
      random term, to take into account the correlation between family members. We
      estimate the parameters using maximum likelihood based on the combined joint
      likelihood (CJL) approach. Simulations show that the CJL is more efficient for
      estimating the NIMA odds ratios as compared to a families-only approach. To
      illustrate our approach, we used data from a family and a twin study from the
      United Kingdom on rheumatoid arthritis, and confirmed the protective NIMA effect,
      with an odds ratio of 0.477 (95% CI 0.264-0.864). 

PMID- 22851507
TI  - Reference-free unwarping of EPI data using dynamic off-resonance correction with
      multiecho acquisition (DOCMA).
AB  - Inhomogeneities of the main magnetic field cause geometric distortion in echo
      planar imaging, a method central to functional MRI. A number of correction
      methods have been proposed, most of which are based on the acquisition of a
      fieldmap providing the local offsets to the main magnetic field. Here,
      accelerated multiecho echo-planar imaging is used, with echo times short enough
      to enable the construction of a fieldmap of comparable quality from the data
      themselves. This way, each volume in a time series can be unwarped using a
      fieldmap obtained from that volume, avoiding volume-to-volume field-motion
      interactions that invalidate reference data in conventional approaches that use a
      single, static, fieldmap. The combination of accelerated acquisition with dynamic
      distortion correction yields volumes with very low distortion at repetition times
      similar to conventional echo-planar imaging. The method is applied to data
      acquired at 3 and 7 T and is shown to effectively correct image geometry.
      Furthermore, it is shown that dynamic distortion correction yields better
      temporal signal stability than correction using a static fieldmap in the presence
      of subject motion.

PMID- 22851508
TI  - Embryonic NANOG activity defines colorectal cancer stem cells and modulates
      through AP1- and TCF-dependent mechanisms.
AB  - Embryonic NANOG (NANOG1) is considered as an important regulator of pluripotency
      while NANOGP8 (NANOG-pseudogene) plays a role in tumorigenesis. Herein, we show
      NANOG is expressed from both NANOG1 and NANOGP8 in human colorectal cancers
      (CRC). Enforced NANOG1-expression increases clonogenic potential and tumor
      formation in xenograft models, although it is expressed only in a small
      subpopulation of tumor cells and is colocalized with endogenous nuclear beta
      catenin(High) . Moreover, single NANOG1-CRCs form spherical aggregates, similar
      to the embryoid body of embryonic stem cells (ESCs), and express higher levels of
      stem-like Wnt-associated target genes. Furthermore, we show that NANOG1
      expression is positively regulated by c-JUN and beta-catenin/TCF4. Ectopic
      expression of c-Jun in murine Apc(Min/+) -ESCs results in the development of
      larger xenograft tumors with higher cell density compared to controls. Chromatin
      immunoprecipitation assays demonstrate that c-JUN binds to the NANOG1-promoter
      via the octamer M1 DNA element. Collectively, our data suggest that beta
      Catenin/TCF4 and c-JUN together drive a subpopulation of CRC tumor cells that
      adopt a stem-like phenotype via the NANOG1-promoter.

PMID- 22851509
TI  - Review of hepatocellular cancer, hypertension and renal impairment as late
      complications of acute porphyria and recommendations for patient follow-up.
AB  - This review critically appraises the data emerging from small retrospective and
      prospective cohort studies suggesting that patients with the autosomal dominant
      acute porphyrias may be at increased risk of hepatocellular cancer (HCC),
      hypertension (HT) and renal impairment. The most striking finding is a marked
      excess risk of HCC in Swedish patients with acute intermittent porphyria (AIP).
      As Sweden has a relatively high prevalence of AIP due to a founder effect, it is
      uncertain to what extent the finding is generalisable to other populations or
      other acute porphyrias and whether early intervention through screening can
      improve outcomes. As yet there is no evidence for the cost-effectiveness of
      systematic surveillance for HCC in acute porphyria outside Sweden. Data from
      several populations also suggest a high prevalence of chronic sustained HT and
      renal impairment in AIP, but it is uncertain if this represents a true excess
      risk, in particular for asymptomatic patients. As these long-term complications
      are important and potentially treatable, a pragmatic recommendation is that
      symptomatic patients with acute porphyria should be offered specialist long-term
      follow-up and, for those aged >50 years, annual liver ultrasound may be
      considered following discussion of the likely risks and benefits. Opportunistic
      cardiovascular risk assessment can readily be incorporated into a structured
      annual review so that appropriate drugs safe for use in acute porphyria are
      prescribed promptly. As these diseases are rare, collaborative international
      epidemiological studies such as those being coordinated through the European
      Porphyria Network are essential to inform best clinical practice.

PMID- 22851510
TI  - Performance evaluation of the Sysmex haematology XN modular system.
AB  - BACKGROUND: The Sysmex XN haematology instrument performs automatic reflex
      testing, depending on sample results. A nucleated red blood cell (NRBC) count is
      provided on all samples. The instrument has a smaller footprint (34%) than
      previous Sysmex XE analysers. METHODS: An evaluation comparing all results to the
      Sysmex XE-2100 and manual microscopic differential and morphology (n=390) was
      performed followed by a workflow study of 1000 samples to compare speed of
      operation and number of blood films reviews required from both systems. RESULTS:
      The new features on the instrument are: (1) white cell and NRBC channel, all
      samples include the NRBC count; (2) white cell precursor channel: false positive
      flags for blasts, abnormal lymphocytes and atypical lymphocytes are reduced
      significantly without a statistical increase of false negatives; (3) low white
      cell count mode: suggested setting of <0.5*10(9)/l. An extended count is more
      precise and provides an accurate differential. Fluorescent platelet count is
      performed in a dedicated channel. If the red cell or platelet size histograms are
      abnormal or if the platelet count is low, then a fluorescent platelet count is
      automatically performed. Good correlation with the XE-2100 and manual
      differential was found and the improved results compared to the reference flow
      cytometric analysis for platelet counts, especially below 30*10(9)/l (XE-2100,
      R(2)=0.500; XN, R(2)=0.875). CONCLUSION: The XN showed reduced sample turnaround
      time of 10% and reduced number of blood films for examination, 49% less than the
      XE-2100 without loss of sensitivity with more precise and accurate results on low
      cell counts.

PMID- 22851511
TI  - Batch effect removal methods for microarray gene expression data integration: a
      survey.
AB  - Genomic data integration is a key goal to be achieved towards large-scale genomic
      data analysis. This process is very challenging due to the diverse sources of
      information resulting from genomics experiments. In this work, we review methods
      designed to combine genomic data recorded from microarray gene expression (MAGE)
      experiments. It has been acknowledged that the main source of variation between
      different MAGE datasets is due to the so-called 'batch effects'. The methods
      reviewed here perform data integration by removing (or more precisely attempting
      to remove) the unwanted variation associated with batch effects. They are
      presented in a unified framework together with a wide range of evaluation tools,
      which are mandatory in assessing the efficiency and the quality of the data
      integration process. We provide a systematic description of the MAGE data
      integration methodology together with some basic recommendation to help the users
      in choosing the appropriate tools to integrate MAGE data for large-scale
      analysis; and also how to evaluate them from different perspectives in order to
      quantify their efficiency. All genomic data used in this study for illustration
      purposes were retrieved from InSilicoDB http://insilico.ulb.ac.be. 

PMID- 22851512
TI  - Systematic analysis of the Plk-mediated phosphoregulation in eukaryotes.
AB  - Substantial evidence has confirmed that Polo-like kinases (Plks) play a crucial
      role in a variety of cellular processes via phosphorylation-mediated signaling
      transduction. Identification of Plk phospho-binding proteins and phosphorylation
      substrates is fundamental for elucidating the molecular mechanisms of Plks. Here,
      we present an integrative approach for the analysis of Plk-specific phospho
      binding and phosphorylation sites (p-sites) in proteins. From the currently
      available phosphoproteomic data, we predicted tens of thousands of potential Plk
      phospho-binding and phosphorylation sites in eukaryotes, respectively.
      Furthermore, statistical analysis suggested that Plk phospho-binding proteins are
      more closely implicated in mitosis than their phosphorylation substrates.
      Additional computational analysis together with in vitro and in vivo experimental
      assays demonstrated that human Mis18B is a novel interacting partner of Plk1,
      while pT14 and pS48 of Mis18B were identified as phospho-binding sites. Taken
      together, this systematic analysis provides a global landscape of the complexity
      and diversity of potential Plk-mediated phosphoregulation, and the prediction
      results can be helpful for further experimental investigation.

PMID- 22851513
TI  - Taxonomic binning of metagenome samples generated by next-generation sequencing
      technologies.
AB  - Metagenome research uses random shotgun sequencing of microbial community DNA to
      study the genetic sequences of its members without cultivation. This development
      has been strongly supported by improvements in sequencing technologies, which
      have rendered sequencing cheaper than before. As a consequence, downstream
      computational analysis of metagenome sequence samples is now faced with large
      amounts of complex data. One of the essential steps in metagenome analysis is
      reconstruction of draft genomes for populations of a community or of draft 'pan
      genomes' for higher level clades. 'Taxonomic binning' corresponds to the process
      of assigning a taxonomic identifier to sequence fragments, based on information
      such as sequence similarity, sequence composition or read coverage. This is used
      for draft genome reconstruction, if sequencing coverage is insufficient for
      reconstruction based on assembly information alone. Subsequent functional and
      metabolic annotation of draft genomes allows a genome-level analysis of novel
      uncultured microbial species and even inference of their cultivation
      requirements.

PMID- 22851514
TI  - 1,7-octadiene-assisted tandem multicomponent cross-enyne metathesis (CEYM)-Diels
      Alder reactions: a useful alternative to Mori's conditions.
AB  - The use of 1,7-octadiene as an in situ source of ethylene led us to develop a
      novel multicomponent tandem cross-enyne metathesis (CEYM)-Diels-Alder reaction.
      The process can be considered a relay metathesis, in which the ethylene liberated
      in the ring-closing metathesis (RCM) of 1,7-octadiene initiates the tandem
      sequence. Aliphatic, aromatic, and fluorinated alkynes and several dienophiles
      are compatible with the process, which is particularly efficient with aromatic
      alkynes. This methodology constitutes a useful variant of Mori's conditions in
      CEYM-related reactions.

PMID- 22851515
TI  - Formation of a nitrogenase P-cluster [Fe8S7] core via reductive fusion of two all
      ferric [Fe4S4] clusters.

PMID- 22851516
TI  - Integrative analysis of cancer prognosis data with multiple subtypes using
      regularized gradient descent.
AB  - In cancer research, high-throughput profiling studies have been extensively
      conducted, searching for genes/single nucleotide polymorphisms (SNPs) associated
      with prognosis. Despite seemingly significant differences, different subtypes of
      the same cancer (or different types of cancers) may share common susceptibility
      genes. In this study, we analyze prognosis data on multiple subtypes of the same
      cancer but note that the proposed approach is directly applicable to the analysis
      of data on multiple types of cancers. We describe the genetic basis of multiple
      subtypes using the heterogeneity model that allows overlapping but different sets
      of susceptibility genes/SNPs for different subtypes. An accelerated failure time
      (AFT) model is adopted to describe prognosis. We develop a regularized gradient
      descent approach that conducts gene-level analysis and identifies genes that
      contain important SNPs associated with prognosis. The proposed approach belongs
      to the family of gradient descent approaches, is intuitively reasonable, and has
      affordable computational cost. Simulation study shows that when prognosis
      associated SNPs are clustered in a small number of genes, the proposed approach
      outperforms alternatives with significantly more true positives and fewer false
      positives. We analyze an NHL (non-Hodgkin lymphoma) prognosis study with SNP
      measurements and identify genes associated with the three major subtypes of NHL,
      namely, DLBCL, FL, and CLL/SLL. The proposed approach identifies genes different
      from using alternative approaches and has the best prediction performance. 

PMID- 22851517
TI  - The effect of concomitant gradient fields on diffusion tensor imaging.
AB  - Concomitant gradient fields are transverse magnetic field components that are
      necessarily present to satisfy Maxwell's equations when magnetic field gradients
      are utilized in magnetic resonance imaging. They can have deleterious effects
      that are more prominent at lower static fields and/or higher gradient strengths.
      In diffusion tensor imaging schemes that employ large gradients that are not
      symmetric about a refocusing radiofrequency pulse (unlike Stejskal-Tanner, which
      is symmetric), concomitant fields may cause phase accrual that could corrupt the
      diffusion measurement. Theory predicting the error from this dephasing is
      described and experimentally validated for both Reese twice-refocused and split
      gradient single spin-echo diffusion gradient schemes. Bias in apparent diffusion
      coefficient values was experimentally found to worsen with distance from
      isocenter and with increasing duration of gradient asymmetry in both a phantom
      and in the brain. The amount of error from concomitant gradient fields depends on
      many variables, including the diffusion gradient pattern, pulse sequence timing,
      maximum effective gradient amplitude, static magnetic field strength, voxel size,
      slice distance from isocenter, and partial Fourier fraction. A prospective
      correction scheme that can reduce concomitant gradient errors is proposed and
      verified for diffusion imaging.

PMID- 22851519
TI  - Dy(III)- and Yb(III)-curcuminoid compounds: original fluorescent single-ion
      magnet and magnetic near-IR luminescent species.
AB  - The multifunctional behavior of two mononuclear lanthanide compounds attached to
      a curcuminoid called 9 Accm has been investigated. The results show that [Dy(9
      Accm)(2)(NO(3))(dmf)(2)] Yb(9 Accm)(3)(py)] behaves as a single-ion magnet and
      that both compounds display luminescent responses and exhibit affinity for
      graphite surfaces (see figure).

PMID- 22851518
TI  - Skin-derived precursors as a source of progenitors for cutaneous nerve
      regeneration.
AB  - Peripheral nerves have the potential to regenerate axons and reinnervate end
      organs. Chronic denervation and disturbed nerve regeneration are thought to
      contribute to peripheral neuropathy, pain, and pruritus in the skin. The capacity
      of denervated distal nerves to support axonal regeneration requires proliferation
      by Schwann cells, which guide regenerating axons to their denervated targets.
      However, adult peripheral nerve Schwann cells do not retain a growth-permissive
      phenotype, as is required to produce new glia. Therefore, it is believed that
      following injury, mature Schwann cells dedifferentiate to a progenitor/stem cell
      phenotype to promote axonal regrowth. In this study, we show that skin-derived
      precursors (SKPs), a recently identified neural crest-related stem cell
      population in the dermis of skin, are an alternative source of progenitors for
      cutaneous nerve regeneration. Using in vivo and in vitro three-dimensional
      cutaneous nerve regeneration models, we show that the SKPs are neurotropic toward
      injured nerves and that they have a full capacity to differentiate into Schwann
      cells and promote axon regeneration. The identification of SKPs as a physiologic
      source of progenitors for cutaneous nerve regeneration in the skin, where SKPs
      physiologically reside, has important implications for understanding early
      cellular events in peripheral nerve regeneration. It also provides fertile ground
      for the elucidation of intrinsic and extrinsic factors within the nerve
      microenvironment that likely play essential roles in cutaneous nerve homeostasis.

PMID- 22851520
TI  - Functional imaging of the brainstem and cortical sites of autonomic control in
      human subjects.

PMID- 22851521
TI  - Investigation of heavy metal pollution of trees in a contaminated industrial area
      in the north of Iran.
AB  - Phytoremediation is the technology of purging soils and water systems from heavy
      pollutant metals. Cadmium is one of the heavy elements, which is environmentally
      important due to its toxicity to humans and animals. Toxicity and accumulation of
      cadmium in body organs through eating contaminated food has an important role in
      endangering human's health. To this end, trees of buttonwood were prepared and
      irrigated with nutrient solution containing cadmium chloride in 10, 15 and 20 mM
      for 12 months. Then the root, stem and leaf samples were harvested and the
      amounts of cadmium element in stem, root and leaf organs together with the growth
      parameters were measured. This study determined the amount of cadmium accumulated
      by Platanus occidentalis. Furthermore, the comparison between accumulation and
      transfer of cadmium in the study showed that absorption of this metal by the root
      is more than its amount in stem and leaf. The result of this research shows that
      buttonwood has the potential for cadmium accumulation without any serious damage
      to its growth. Regarding the extent of contaminated industrial areas,
      petrochemical industry, power plants and vast contaminated municipal areas, there
      is a great need for planting fast-growing and tolerant plants like buttonwood.

PMID- 22851522
TI  - Skin decontamination: principles and perspectives.
AB  - Skin decontamination is the primary intervention needed in chemical, biological
      and radiological exposures, involving immediate removal of the contaminant from
      the skin performed in the most efficient way. The most readily available
      decontamination system on a practical basis is washing with soap and water or
      water only. Timely use of flushing with copious amounts of water may physically
      remove the contaminant. However, this traditional method may not be completely
      effective, and contaminants left on the skin after traditional washing procedures
      can have toxic consequences. This article focuses on the principles and practices
      of skin decontamination. 

PMID- 22851523
TI  - The effect of exposure to chlorine on pulmonary function tests and respiratory
      and allergic symptoms in Iranian lifeguards.
AB  - Lifeguards are frequently exposed to various irritant chemicals including
      chlorine during work, which can induce respiratory and allergic disorders. In
      this study, pulmonary function tests (PFTs) and self-reported respiratory and
      allergic symptoms in lifeguards were compared with matched control subjects. The
      frequency of respiratory and allergic symptoms was evaluated in a sample of 38
      Iranian male lifeguards and 38 control subjects with similar age, having other
      jobs from the general population, using a questionnaire including questions on
      work-related respiratory and allergic symptoms in the past year, smoking habits,
      and duration of working as a lifeguard. PFTs were also measured in lifeguard
      subjects before and 15 min after 200 ug inhaled salbutamol and baseline PFT in
      controls. A total of 22 (55%) participants reported work-related respiratory
      symptoms. Sputum (39.4%) and cough (18.4%) were the most common symptoms and only
      7.9% and 15.8% of lifeguards reported wheezing and shortness of breath,
      respectively. Both sputum and breathlessness were significantly higher in
      lifeguards than control group (p < 0.05 and p < 0.005, respectively). Most
      allergic symptoms (sneezing and runny nose) in lifeguards were also significantly
      greater than control group (p < 0.05 for both cases). In addition, all
      respiratory (except sputum and wheezing) and allergic symptoms were significantly
      higher in lifeguards during work compared with rest period (p < 0.05 to p <
      0.005). Most PFT values were also significantly lower in lifeguards than control
      subjects (p < 0.05 to p < 0.001). In addition, most (all) PFT values were
      significantly improved after 200 ug inhaled salbutamol (p < 0.05 to p < 0.001).
      These results showed that lifeguards have higher frequencies of work related
      respiratory symptoms and allergic symptoms particularly during the work period.
      PFT values were also significantly reduced among lifeguards. 

PMID- 22851524
TI  - Assessment of total aflatoxin level in red pepper obtained from Istanbul.
AB  - Aflatoxins (Aspergillus flavus toxins (AFT)) are biologically active secondary
      metabolites mostly produced by some Aspergillus species that causes
      hepatotoxicity, teratogenicity, immunotoxicity, and cancers in human. The aim of
      this study is to determine the level of total AFT in powdered red pepper in the
      retail markets in 40 district of Istanbul using enzyme-linked immunosorbent
      assay. Of the 36 unpacked powdered red pepper samples, 32 samples (88%) contained
      AFT in the range of 0.2-106.4 ug/kg; 16 samples (44.4%) were above the regulatory
      limit which is at 10 ug/kg for total AFT in Turkey. More precautions on the
      production, transport, harvest, and storage of red pepper should be taken on
      hygiene to prevent toxic and carcinogenic effects of AFT. 

PMID- 22851526
TI  - Paclitaxel-coated versus uncoated balloon angioplasty reduces target lesion
      revascularization in patients with femoropopliteal arterial disease: a meta
      analysis of randomized trials.
AB  - BACKGROUND: In disease of the femoropopliteal artery, paclitaxel-coated balloon
      (PCB) therapy improved angiographic outcomes as compared with uncoated balloon
      (UCB) angioplasty. Nevertheless, it remains uncertain whether PCB may reduce the
      need for reintervention. METHODS AND RESULTS: We searched Medline, EMBASE, the
      Cochrane Central Register of Controlled Trials (CENTRAL), scientific session
      abstracts, and relevant web sites for trials of PCB versus UCB angioplasty. Key
      words were: "superficial femoral artery," "popliteal artery," "angioplasty,"
      "drug-eluting balloon," "paclitaxel-eluting balloon," and "randomized trial."
      Inclusion criteria were: (1) randomized design; (2) intention-to-treat analysis;
      and (3) >=6-month follow-up. Exclusion criteria were: (1) vessel treated other
      than femoropopliteal artery; (2) device used other than PCB/UCB; and (3)
      irretrievable or duplicated data. No restrictions (language, publication date, or
      status) were applied. The primary end point was target lesion revascularization.
      Secondary end points were: angiographic binary restenosis and late lumen loss and
      all-cause mortality. A total of 381 patients enrolled in 4 randomized trials were
      included (PCB, n=186 versus UCB, n=195). Median follow-up was 10.3 months.
      Angioplasty with PCB versus UCB reduces target lesion revascularization (12.2%
      versus 27.7%; OR, 0.22; 95% CI, 0.13-0.38; P<0.00001), angiographic restenosis
      (18.7% versus 45.5%; OR, 0.26; 95% CI, 0.14-0.48; P<0.0001), and late lumen loss
      (range, -0.05 to 0.50 mm versus 0.61-1.7 mm; weighted mean difference, -0.75 mm;
      95% CI, -1.06 to -0.45; P<0.00001). No mortality difference was observed for PCB
      versus UCB (2.1% versus 3.2%; OR, 0.99; 95% CI, 0.39-2.49; P=0.98). CONCLUSIONS:
      In femoropopliteal arterial disease, PCB therapy is associated with superior
      antirestenotic efficacy as compared with UCB angioplasty with no evidence of a
      differential safety profile.

PMID- 22851525
TI  - The long-term effect of coronary stenting on epicardial and microvascular
      endothelial function.
AB  - BACKGROUND: Coronary stents, drug-eluting stents in particular, have been linked
      to coronary epicardial endothelial dysfunction after implantation. However, less
      is known about their impact on coronary microvascular function and their long
      term effects on the vasculature. METHODS AND RESULTS: We evaluated 71 patients
      (mean age, 53.0+/-10.1 years) with chest pain and angiographically nonsignificant
      coronary artery disease 17.1+/-17.1 months after left anterior descending
      coronary artery stenting. Seventy-one age- and sex-matched patients (mean age,
      53.0+/-10.3 years) with chest pain but no prior coronary intervention served as
      controls. Coronary blood flow in response to the endothelium-dependent
      vasodilator acetylcholine as well as the microvascular (endothelium-independent)
      coronary flow reserve in response to intracoronary adenosine were evaluated.
      Quantitative coronary angiography was used to study epicardial diameter changes
      to acetylcholine. Microcirculatory function was not significantly different
      between the stenting and control groups (median [interquartile range] coronary
      flow reserve, 2.9 [2.5-3.4] versus 3.0 [2.4-3.4] mL/min, P=0.24; change of
      coronary blood flow, 34.9% [-34.4% to 90.0%] versus 54.7% [-5.6% to 104.6%],
      P=0.18). Both groups exhibited epicardial endothelial dysfunction (-23.0% [-47.4%
      to -7.6%] versus -20.0% [-40.0% to 0.0%], P=0.4). Results did not differ between
      patients with drug-eluting stents (n=46) and patients with bare-metal stents
      (n=24). CONCLUSIONS: This study demonstrates that in patients with coronary
      arteries in which a stent has been placed, coronary microcirculatory and
      epicardial vascular function are not significantly different from that of an age-
      and sex-matched population with similar symptoms but nonsignificant coronary
      artery disease.

PMID- 22851527
TI  - Clinical and stent-related outcomes after transcatheter or operative placement of
      bare-metal stents in the ventricular septum or subvalvar systemic outflow tract.
AB  - BACKGROUND: Stenting of the systemic ventricular outflow tract and creation or
      enlargement of a ventricular septal defect using stents are potential therapeutic
      options in rare patients with congenital heart disease who develop significant
      ventricular hypertension due to outflow obstruction. These stents may be at
      increased risk of fracture because of exposure to cyclic compressive stresses.
      The objective of this study was to evaluate the safety and efficacy of this
      intervention and to determine the incidence of stent fracture and other adverse
      outcomes after placement of intraventricular or interventricular stents for this
      indication. METHODS AND RESULTS: Between 1992 and 2010, 27 patients underwent
      bare-metal stent placement in the ventricular septum or subvalvar systemic
      outflow tract, using 1 of the following 3 delivery approaches: (1) percutaneous
      (n=18), (2) intraoperative (n=8), and (3) hybrid (n=1). The median ventricular-to
      aortic systolic pressure ratio decreased from 1.7 (1.3-2.6) to 1.1 (0.9-1.8)
      (P<0.001). Survival free from surgical reintervention for outflow obstruction was
      92% at 1 year and 66% at 3 years. Stent fracture was diagnosed in 11 patients
      (41%) a median of 2.6 years (0.03-7.8 years) after stent placement and was always
      associated with recurrent obstruction. Survival free from diagnosis of stent
      fracture was 84% at 1 year and 73% at 3 years. Other adverse events included
      complete heart block (n=2) and increased atrioventricular valve regurgitation
      requiring surgical intervention (n=2). CONCLUSIONS: Transcatheter,
      intraoperative, or hybrid stenting of the ventricular septum or systemic outflow
      tract is feasible and effective in the short term. Stent fractures were common
      during follow-up and associated with recurrent obstruction.

PMID- 22851528
TI  - Clinical and procedural predictors of suboptimal outcome after the treatment of
      drug-eluting stent restenosis in the unprotected distal left main stem: the Milan
      and New-Tokyo (MITO) registry.
AB  - BACKGROUND: Few data are available regarding the optimal revascularization
      strategy for unprotected distal left main coronary artery (UDLM) in-stent
      restenosis (ISR). METHODS AND RESULTS: Between April 2002 and December 2008, UDLM
      ISR following drug-eluting stent (DES) implantation occurred in 92 of 474
      patients (19.4%). Of these, 8 (8.7%) who underwent a coronary artery bypass graft
      (CABG) were excluded, and the remaining 84 (91.3%) who underwent percutaneous
      coronary intervention (PCI) (43 plain old balloon angioplasty [POBA] and 41 DES)
      were analyzed to assess the feasibility of PCI for UDLM-ISR. The overall cardiac
      death, myocardial infarction (MI), and major adverse cardiac events during the
      follow-up period (median, 24 months) occurred in 4, 2, and 31 patients,
      respectively. Repeat target lesion revascularization (TLR) occurred in 28
      patients. The incidence of repeat TLR was higher following PCI with POBA than
      with DES (hazard ratio [HR], 2.79; 95% CI, 1.23-6.34; P=0.014). On Cox regression
      analysis, the independent predictors of repeat TLR were treatment with POBA (HR,
      3.29; 95% CI, 1.41-7.69; P=0.006) and EuroSCORE (European System for Cardiac
      Operative Risk Evaluation) >6 (HR, 2.53; 95% CI, 1.02-6.28; P=0.045). More
      complex lesions requiring a 2-stent strategy were associated with a higher
      occurrence of TLR for restenosis of the left circumflex coronary artery ostium
      (LCX-ISR) (HR, 2.51; 95% CI, 1.59-3.97; P=0.001) as well as repeat TLR for
      recurrent LCX-ISR (HR, 4.32; 95% CI, 0.97-19.20; P=0.05) compared to a 1-stent
      strategy. No cardiac death at 2 years occurred in patients with LCX-ISR.
      CONCLUSIONS: UDLM restenosis is better treated with DES than with POBA. The rate
      of recurrent ISR following repeat PCI was high, whereas the rates of MI and death
      were relatively low. Complex lesions requiring a 2-stent strategy had a higher
      recurrence rate at the ostial LCX but without an associated increased risk of MI
      and death.

PMID- 22851530
TI  - PRISM: pair-read informed split-read mapping for base-pair level detection of
      insertion, deletion and structural variants.
AB  - MOTIVATION: The development of high-throughput sequencing technologies has
      enabled novel methods for detecting structural variants (SVs). Current methods
      are typically based on depth of coverage or pair-end mapping clusters. However,
      most of these only report an approximate location for each SV, rather than exact
      breakpoints. RESULTS: We have developed pair-read informed split mapping (PRISM),
      a method that identifies SVs and their precise breakpoints from whole-genome
      resequencing data. PRISM uses a split-alignment approach informed by the mapping
      of paired-end reads, hence enabling breakpoint identification of multiple SV
      types, including arbitrary-sized inversions, deletions and tandem duplications.
      Comparisons to previous datasets and simulation experiments illustrate PRISM's
      high sensitivity, while PCR validations of PRISM results, including previously
      uncharacterized variants, indicate an overall precision of ~90%. AVAILABILITY:
      PRISM is freely available at http://compbio.cs.toronto.edu/prism.

PMID- 22851531
TI  - MetiTree: a web application to organize and process high-resolution multi-stage
      mass spectrometry metabolomics data.
AB  - Identification of metabolites using high-resolution multi-stage mass spectrometry
      (MS(n)) data is a significant challenge demanding access to all sorts of
      computational infrastructures. MetiTree is a user-friendly, web application
      dedicated to organize, process, share, visualize and compare MS(n) data. It
      integrates several features to export and visualize complex MS(n) data,
      facilitating the exploration and interpretation of metabolomics experiments. A
      dedicated spectral tree viewer allows the simultaneous presentation of three
      related types of MS(n) data, namely, the spectral data, the fragmentation tree
      and the fragmentation reactions. MetiTree stores the data in an internal database
      to enable searching for similar fragmentation trees and matching against other
      MS(n) data. As such MetiTree contains much functionality that will make the
      difficult task of identifying unknown metabolites much easier. AVAILABILITY:
      MetiTree is accessible at http://www.MetiTree.nl. The source code is available at
      https://github.com/NetherlandsMetabolomicsCentre/metitree/wiki.

PMID- 22851529
TI  - Red fluorescent proteins: advanced imaging applications and future design.
AB  - In the past few years a large series of the advanced red-shifted fluorescent
      proteins (RFPs) has been developed. These enhanced RFPs provide new possibilities
      to study biological processes at the levels ranging from single molecules to
      whole organisms. Herein the relationship between the properties of the RFPs of
      different phenotypes and their applications to various imaging techniques are
      described. Existing and emerging imaging approaches are discussed for
      conventional RFPs, far-red FPs, RFPs with a large Stokes shift, fluorescent
      timers, irreversibly photoactivatable and reversibly photoswitchable RFPs.
      Advantages and limitations of specific RFPs for each technique are presented.
      Recent progress in understanding the chemical transformations of red chromophores
      allows the future RFP phenotypes and their respective novel imaging applications
      to be foreseen.

PMID- 22851533
TI  - Temporary electrostatic impairment of DNA recognition: light-driven DNA binding
      of peptide dimers.

PMID- 22851535
TI  - Behavior of urban residents toward the discarding of waste electrical and
      electronic equipment: a case study in Baoding, China.
AB  - The volume of waste electrical and electronic equipment (WEEE) is growing rapidly
      worldwide, making its management difficult; therefore, this should be improved as
      a matter of urgency. WEEE includes both essential household appliances [including
      televisions, refrigerators, and washing machines; but not air conditioners, where
      the consumption mode is more like information, communication and technology
      (ICT)] ICT equipment (also called high-tech household appliances). In the present
      study, Baoding, a medium-sized, prefecture-level city in north central China with
      a population of 11 million, including 1.1 million urban residents, was selected
      as a representative city for an investigation of recycling behaviors. A valid
      sample size of 346 households in Baoding was investigated, and categorized into
      various income and educational levels. The results showed that the major reason
      for discarding WEEE was malfunction of the appliance, accounting for 52% of
      disposals. Surveyed households with either high income or good education were
      more likely to consume high-tech household appliances, attracted by advanced
      technology, versatile functions or flexibility of use. Personal computer
      ownership rates were highest in households with a high income and good education
      1.2 and 0.9 per home respectively. WEEE was most often sold to peddlers or
      hawkers from where the WEEE flowed into the second-hand market to be refurbished
      or repaired, and then re-sold. However, 56.3% of residents in the college
      community were in support of charging consumers for disposal and 61.7% were in
      support of including a disposal surcharge in the purchase price of new products-a
      percentage approximately three times that for high-income residents. Thus, high
      educational level appears to be currently the most important factor in raising
      the potential of a household's willingness to pay for WEEE treatment cost. The
      findings of this study can be used to develop sound recycling systems for WEEE in
      mainland China.

PMID- 22851536
TI  - E-waste: a problem or an opportunity? Review of issues, challenges and solutions
      in Asian countries.
AB  - Safe management of electronic and electrical waste (e-waste/WEEE) is becoming a
      major problem for many countries around the world. In particular, developing
      countries face a number of issues with the generation, transboundary movement and
      management of e-waste. It is estimated that the world generates around 20-50
      million tonnes of e-waste annually, most of it from Asian countries. Improper
      handling of e-waste can cause harm to the environment and human health because of
      its toxic components. Several countries around the world are now struggling to
      deal with this emerging threat. Although the current emphasis is on end-of-life
      management of e-waste activities, such as reuse, servicing, remanufacturing,
      recycling and disposal, upstream reduction of e-waste generation through green
      design and cleaner production is gaining much attention. Environmentally sound
      management (ESM) of e-waste in developing countries is absent or very limited.
      Transboundary movement of e-waste is a major issue throughout the region. Dealing
      with the informal recycling sector is a complex social and environmental issue.
      There are significant numbers of such challenges faced by these countries in
      achieving ESM of e-waste. This article aims to present a review of challenges and
      issues faced by Asian countries in managing their e-waste in a sustainable way.

PMID- 22851534
TI  - Simultaneous control of diabetes mellitus, hypertension, and hyperlipidemia in 2
      health systems.
AB  - BACKGROUND: Many individuals with diabetes mellitus, hypertension, and
      hyperlipidemia have difficulty achieving control of all 3 conditions. We assessed
      the incidence and duration of simultaneous control of hyperglycemia, blood
      pressure, and low-density lipoprotein cholesterol in patients from 2 health care
      systems in Colorado. METHODS AND RESULTS: We performed a retrospective cohort
      study of adults at Denver Health and Kaiser Permanente Colorado with diabetes
      mellitus, hypertension, and hyperlipidemia from 2000 through 2008. Over a median
      of 4.0 and 4.4 years, 16% and 30% of individuals at Denver Health and Kaiser
      Permanente achieved the primary outcome (simultaneous control with a glycosylated
      hemoglobin (HbA(1c)) <7.0%, blood pressure <130/80 mm Hg, and low-density
      lipoprotein cholesterol <100 mg/dL), respectively. With less strict goals
      (HbA(1c) <8.0%, blood pressure <140/90 mm Hg, and low-density lipoprotein
      cholesterol <130 mg/dL), 44% and 70% of individuals at Denver Health and Kaiser
      Permanente achieved simultaneous control. Sociodemographic characteristics
      (increasing age, white ethnicity), and the presence of cardiovascular disease or
      other comorbidities were significantly but not strongly predictive of achieving
      simultaneous control in multivariable models. Simultaneous control was less
      likely as severity of the underlying conditions increased, and more likely as
      medication adherence increased. CONCLUSIONS: Simultaneous control of diabetes
      mellitus, hypertension, and hyperlipidemia was uncommon and generally transient.
      Less stringent goals had a relatively large effect on the proportion achieving
      simultaneous control. Individuals who simultaneously achieve multiple treatment
      goals may provide insight into self-care strategies for individuals with comorbid
      health conditions.

PMID- 22851537
TI  - Asthma mortality among Brazilian children up to 19 years old between 1980 and
      2007.
AB  - OBJECTIVE: To evaluate asthma mortality among Brazilian children up to 19 years
      old in 1980 to 2007. METHODS: This ecological time-series study used the database
      of the Brazilian Unified Health System, from which data were collected about the
      number of asthma deaths and the population under 19 years of age in Brazil.
      Mortality rates were calculated as the number of asthma deaths divided by
      population and multiplied by 100,000. Linear regression was used to assess the
      trend of mortality. For the analysis, participants were assigned to three
      separate age groups: 1-4 years, 5-9 years and 10-19 years. RESULTS: During the
      study period, there were 9,051 deaths due to asthma in children under 19 years of
      age. Of these, 69% (6,270 records) of the children were younger than 5 years.
      There was a significant decrease in asthma mortality during the study in all age
      groups. The mean annual reduction of asthma mortality rates among children was
      0.022 (p < 0.0001). The reduction was 0.076, 0.005 and 0.004 for the 1- to 4-, 5-
      to 9- and 10- to 19-year-old age groups (p < 0.0001). CONCLUSION: Asthma
      mortality among Brazilian children is low and has kept a downward trend during
      the study in all pediatric age groups.

PMID- 22851538
TI  - Modelling of the whey and cow manure co-digestion process.
AB  - The production of renewable energy, a reduction of waste and prevention of
      environmental pollution promote the industrial application of anaerobic co
      digestion for the treatment of agro-industrial organic waste. In this paper
      production of biogas/methane was studied by performing a series of laboratory
      batch experiments using whey and cow manure as substrates. The influence of
      substrate concentration, temperature and pH on biogas production was analysed. A
      mathematical model has been developed that describes the co-digestion process.
      The hydrolysis of proteins, lipids and cellulose has been modelled using first
      order kinetics. Fermentation of sugars and amino acids, anaerobic oxidation of
      long chain fatty acids (LCFA), acetogenesis and methanogenesis have been
      described using an unstructured model based on Monod kinetic equations taking
      into account different inhibitory effects. Model applicability was demonstrated
      by comparing experimental results with the model simulation results.

PMID- 22851539
TI  - Tracking chromatid segregation to identify human cardiac stem cells that
      regenerate extensively the infarcted myocardium.
AB  - RATIONALE: According to the immortal DNA strand hypothesis, dividing stem cells
      selectively segregate chromosomes carrying the old template DNA, opposing
      accumulation of mutations resulting from nonrepaired replication errors and
      attenuating telomere shortening. OBJECTIVE: Based on the premise of the immortal
      DNA strand hypothesis, we propose that stem cells retaining the old DNA would
      represent the most powerful cells for myocardial regeneration. METHODS AND
      RESULTS: Division of human cardiac stem cells (hCSCs) by nonrandom and random
      segregation of chromatids was documented by clonal assay of bromodeoxyuridine
      tagged hCSCs. Additionally, their growth properties were determined by a series
      of in vitro and in vivo studies. We report that a small class of hCSCs retain
      during replication the mother DNA and generate 2 daughter cells, which carry the
      old and new DNA, respectively. hCSCs with immortal DNA form a pool of
      nonsenescent cells with longer telomeres and higher proliferative capacity. The
      self-renewal and long-term repopulating ability of these cells was shown in
      serial-transplantation assays in the infarcted heart; these cells created a
      chimeric organ, composed of spared rat and regenerated human cardiomyocytes and
      coronary vessels, leading to a remarkable restoration of cardiac structure and
      function. The documentation that hCSCs divide by asymmetrical and symmetrical
      chromatid segregation supports the view that the human heart is a self-renewing
      organ regulated by a compartment of resident hCSCs. CONCLUSIONS: The impressive
      recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs
      carrying the "mother" DNA underscores the clinical relevance of this stem cell
      class for the management of heart failure in humans.

PMID- 22851540
TI  - Nitroxyl-mediated disulfide bond formation between cardiac myofilament cysteines
      enhances contractile function.
AB  - RATIONALE: In the myocardium, redox/cysteine modification of proteins regulating
      Ca(2+) cycling can affect contraction and may have therapeutic value. Nitroxyl
      (HNO), the one-electron-reduced form of nitric oxide, enhances cardiac function
      in a manner that suggests reversible cysteine modifications of the contractile
      machinery. OBJECTIVE: To determine the effects of HNO modification in cardiac
      myofilament proteins. METHODS AND RESULTS: The HNO-donor, 1-nitrosocyclohexyl
      acetate, was found to act directly on the myofilament proteins, increasing
      maximum force (F(max)) and reducing the concentration of Ca(2+) for 50%
      activation (Ca(50)) in intact and skinned cardiac muscles. The effects of 1
      nitrosocyclohexyl acetate are reversible by reducing agents and distinct from
      those of another HNO donor, Angeli salt, which was previously reported to
      increase F(max) without affecting Ca50. Using a new mass spectrometry capture
      technique based on the biotin switch assay, we identified and characterized the
      formation by HNO of a disulfide-linked actin-tropomyosin and myosin heavy chain
      myosin light chain 1. Comparison of the 1-nitrosocyclohexyl acetate and Angeli
      salt effects with the modifications induced by each donor indicated the actin
      tropomyosin and myosin heavy chain-myosin light chain 1 interactions
      independently correlated with increased Ca(2+) sensitivity and force generation,
      respectively. CONCLUSIONS: HNO exerts a direct effect on cardiac myofilament
      proteins increasing myofilament Ca(2+) responsiveness by promoting disulfide bond
      formation between critical cysteine residues. These findings indicate a novel,
      redox-based modulation of the contractile apparatus, which positively impacts
      myocardial function, providing further mechanistic insight for HNO as a
      therapeutic agent.

PMID- 22851541
TI  - Neurodevelopmental outcomes in children with congenital heart disease: evaluation
      and management: a scientific statement from the American Heart Association.
AB  - BACKGROUND: The goal of this statement was to review the available literature on
      surveillance, screening, evaluation, and management strategies and put forward a
      scientific statement that would comprehensively review the literature and create
      recommendations to optimize neurodevelopmental outcome in the pediatric
      congenital heart disease (CHD) population. METHODS AND RESULTS: A writing group
      appointed by the American Heart Association and American Academy of Pediatrics
      reviewed the available literature addressing developmental disorder and
      disability and developmental delay in the CHD population, with specific attention
      given to surveillance, screening, evaluation, and management strategies. MEDLINE
      and Google Scholar database searches from 1966 to 2011 were performed for English
      language articles cross-referencing CHD with pertinent search terms. The
      reference lists of identified articles were also searched. The American College
      of Cardiology/American Heart Association classification of recommendations and
      levels of evidence for practice guidelines were used. A management algorithm was
      devised that stratified children with CHD on the basis of established risk
      factors. For those deemed to be at high risk for developmental disorder or
      disabilities or for developmental delay, formal, periodic developmental and
      medical evaluations are recommended. A CHD algorithm for surveillance, screening,
      evaluation, reevaluation, and management of developmental disorder or disability
      has been constructed to serve as a supplement to the 2006 American Academy of
      Pediatrics statement on developmental surveillance and screening. The proposed
      algorithm is designed to be carried out within the context of the medical home.
      This scientific statement is meant for medical providers within the medical home
      who care for patients with CHD. CONCLUSIONS: Children with CHD are at increased
      risk of developmental disorder or disabilities or developmental delay. Periodic
      developmental surveillance, screening, evaluation, and reevaluation throughout
      childhood may enhance identification of significant deficits, allowing for
      appropriate therapies and education to enhance later academic, behavioral,
      psychosocial, and adaptive functioning.

PMID- 22851542
TI  - Bionic baroreceptor corrects postural hypotension in rats with impaired
      baroreceptor.
AB  - BACKGROUND: Impairment of the arterial baroreflex causes orthostatic hypotension.
      Arterial baroreceptor sensitivity degrades with age. Thus, an impaired
      baroreceptor plays a pivotal role in orthostatic hypotension in most elderly
      patients. There is no effective treatment for orthostatic hypotension. The aims
      of this investigation were to develop a bionic baroreceptor (BBR) and to verify
      whether it corrects postural hypotension. METHODS AND RESULTS: The BBR consists
      of a pressure sensor, a regulator, and a neurostimulator. In 35 Sprague-Dawley
      rats, we vascularly and neurally isolated the baroreceptor regions and attached
      electrodes to the aortic depressor nerve for stimulation. To mimic impaired
      baroreceptors, we maintained intracarotid sinus pressure at 60 mm Hg during
      activation of the BBR. Native baroreflex was reproduced by matching intracarotid
      sinus pressure to the instantaneous pulsatile aortic pressure. The encoding rule
      for translating intracarotid sinus pressure into stimulation of the aortic
      depressor nerve was identified by a white noise technique and applied to the
      regulator. The open-loop arterial pressure response to intracarotid sinus
      pressure (n=7) and upright tilt-induced changes in arterial pressure (n=7) were
      compared between native baroreceptor and BBR conditions. The intracarotid sinus
      pressure-arterial pressure relationships were comparable. Compared with the
      absence of baroreflex, the BBR corrected tilt-induced hypotension as effectively
      as under native baroreceptor conditions (native, -39+/-5 mm Hg; BBR, -41+/-5 mm
      Hg; absence, -63+/-5 mm Hg; P<0.05). CONCLUSIONS: The BBR restores the pressure
      buffering function. Although this research demonstrated feasibility of the BBR,
      further research is needed to verify its long-term effect and safety in larger
      animal models and humans.

PMID- 22851543
TI  - Association between extracellular matrix expansion quantified by cardiovascular
      magnetic resonance and short-term mortality.
AB  - BACKGROUND: Extracellular matrix expansion may be a fundamental feature of
      adverse myocardial remodeling, it appears to be treatable, and its measurement
      may improve risk stratification. Yet, the relationship between mortality and
      extracellular matrix is not clear because of difficulties with its measurement.
      To assess its relationship with outcomes, we used novel, validated cardiovascular
      magnetic resonance techniques to quantify the full spectrum of extracellular
      matrix expansion not readily detectable by conventional cardiovascular magnetic
      resonance. METHODS AND RESULTS: We recruited 793 consecutive patients at the time
      of cardiovascular magnetic resonance without amyloidosis or hypertrophic
      cardiomyopathy as well as 9 healthy volunteers (ages 20-50 years). We measured
      the extracellular volume fraction (ECV) to quantify the extracellular matrix
      expansion in myocardium without myocardial infarction. ECV uses gadolinium
      contrast as an extracellular space marker based on T1 measures of blood and
      myocardium pre- and post-gadolinium contrast and hematocrit measurement. In
      volunteers, ECV ranged from 21.7% to 26.2%, but in patients it ranged from 21.0%
      to 45.8%, indicating considerable burden. There were 39 deaths over a median
      follow-up of 0.8 years (interquartile range 0.5-1.2 years), and 43 individuals
      who experienced the composite end point of death/cardiac transplant/left
      ventricular assist device implantation. In Cox regression models, ECV related to
      all-cause mortality and the composite end point (hazard ratio, 1.55; 95%
      confidence interval, 1.27-1.88 and hazard ratio, 1.48; 95% confidence interval,
      1.23-1.78, respectively, for every 3% increase in ECV), adjusting for age, left
      ventricular ejection fraction, and myocardial infarction size. CONCLUSIONS: ECV
      measures of extracellular matrix expansion may predict mortality as well as other
      composite end points (death/cardiac transplant/left ventricular assist device
      implantation).

PMID- 22851544
TI  - Cytokine therapy with interleukin-2/anti-interleukin-2 monoclonal antibody
      complexes expands CD4+CD25+Foxp3+ regulatory T cells and attenuates development
      and progression of atherosclerosis.
AB  - BACKGROUND: CD4+CD25+Foxp3+ regulatory T cells (Tregs) attenuate atherosclerosis,
      but their therapeutic application by adoptive transfer is limited by the need for
      their expansion in vitro and limited purity. Recently, an interleukin (IL)-2/anti
      IL-2 neutralizing monoclonal antibody (IL-2/anti-IL-2 mAb) complex has been shown
      to expand these Tregs. We examined the capacity of a modified IL-2/anti-IL-2 mAb
      treatment to expand Tregs and inhibit both the progression and development of
      developed atherosclerosis. METHODS AND RESULTS: Six-week old apolipoprotein E
      deficient mice fed a high-fat diet for 8 weeks were administered IL-2/anti-IL-2
      mAb commencing 2 weeks after starting the diet. Tregs in the spleen, lymph node,
      and liver were selectively expanded without affecting CD4+, CD8+, or natural
      killer cells. Tregs were increased in lesions and lesion size reduced. CD4+ T
      cells, macrophages, mature dendritic cells, proliferating cell nuclear antigen+
      cells, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule
      1 were reduced. In anti-CD3-stimulated splenocytes, proliferation and secretion
      of Th1, Th2, and Th17 (IL-17) cytokines and IL-1beta were reduced. To determine
      whether treatment attenuated progression of developed atherosclerosis, 6-week-old
      apolipoprotein E-deficient mice were fed a high-fat diet for 6 weeks, followed by
      IL-2/anti-IL-2 mAb treatment for 6 weeks while continuing the high-fat diet.
      Treatment also increased Tregs without affecting CD4+, CD8+, or natural killer
      cells, suppressed inflammation, and greatly attenuated progression of
      atherosclerosis. CONCLUSIONS: IL-2/anti-IL-2 mAb treatment in vivo attenuates
      atherosclerosis via selective Tregs expansion. The findings suggest that cytokine
      based IL-2/anti-IL-2 mAb complex therapy could represent an attractive approach
      for treating atherosclerosis, because it markedly attenuates progression as well
      as development, by modulating its immunoinflammatory component.

PMID- 22851545
TI  - Endothelium-selective activation of AMP-activated protein kinase prevents
      diabetes mellitus-induced impairment in vascular function and
      reendothelialization via induction of heme oxygenase-1 in mice.
AB  - BACKGROUND: Endothelial damage and dysfunction are crucial mediators that link
      diabetes mellitus with atherosclerotic cardiovascular disease. AMP-activated
      kinase (AMPK) has been implicated in regulation of both energy metabolism and
      vascular homeostasis. The present study investigated whether endothelium
      selective activation of AMPK prevents diabetes mellitus-induced endothelial
      damage and vascular dysfunction by improving reendothelialization in mice.
      METHODS AND RESULTS: Transgenic mice with endothelium-selective expression of a
      constitutively active (CA) AMPK were generated and rendered diabetic by the
      injection of streptozotocin. Relaxation and reendothelialization of carotid
      arteries and circulating numbers of endothelial progenitor cells (EPCs) were
      examined after wire-induced denudation. Bone marrow-derived EPCs were isolated to
      monitor their in vivo and in vitro function. Compared with wild-type littermates,
      the CA-AMPK transgenic mice were resistant to diabetes mellitus-induced
      impairment in endothelium-dependent relaxation and reendothelialization of their
      injured carotid arteries. These changes in the transgenic mice were accompanied
      by increased mobilization of EPCs and enhanced incorporation of EPCs into injured
      blood vessels. Furthermore, EPCs from the transgenic mice exhibited augmented
      adhesion, migration, and tube formation capacities. At the molecular level, the
      expression of heme oxygenase (HO)-1 and the secretion of stromal cell-derived
      factor (SDF)-1alpha were upregulated in EPCs derived from the transgenic mice,
      whereas AMPK-mediated elevation of serum SDF-1alpha levels and improvements of
      EPC function and reendothelialization were all abrogated by pharmacological
      inhibition of heme oxygenase-1. CONCLUSIONS: Endothelium-specific AMPK activation
      is sufficient to protect against diabetes mellitus-induced aggravation of
      vascular injury by promoting EPC function and reendothelialization via
      upregulation of heme oxygenase-1 and SDF-1alpha.

PMID- 22851546
TI  - Red meat consumption and risk of stroke: a meta-analysis of prospective studies.
AB  - BACKGROUND AND PURPOSE: Prospective studies of red meat consumption and risk of
      stroke have provided inconsistent results. We performed a meta-analysis to
      summarize the evidence regarding the effects of red meat (fresh, processed, and
      total) consumption on stroke risk. METHODS: Studies were identified by searching
      the PubMed database through May 26, 2012, and by reviewing the reference lists of
      retrieved articles. Prospective studies that reported relative risks (RR) with
      95% confidence intervals (CI) for the association between red meat consumption
      and risk of stroke were eligible. Results were combined using a random-effects
      model. RESULTS: Five articles including results from 6 prospective studies with
      10 630 cases of stroke and 329 495 participants were included in the meta
      analysis. For each serving per day increase in fresh red meat, processed meat,
      and total red meat consumption, the RR (95% CI) of total stroke were 1.11 (1.03
      1.20), 1.13 (1.03-1.24), and 1.11 (1.06-1.16), respectively, without
      heterogeneity among studies (P>0.16). Among 4 articles with results for stroke
      subtypes, the risk of ischemic stroke was positively associated with consumption
      of fresh red meat (RR, 1.13; 95% CI, 1.00-1.27), processed meat (RR, 1.15; 95%
      CI, 1.06-1.24), and total red meat (RR, 1.12; 95% CI, 1.05-1.19); no
      statistically significant associations were observed for hemorrhagic stroke.
      CONCLUSIONS: Results from this meta-analysis indicate that consumption of fresh
      red meat and processed red meat as well as total red meat is associated with
      increased risk of total stroke and ischemic stroke, but not hemorrhagic stroke.

PMID- 22851547
TI  - Retrospective multicenter study of Solitaire FR for revascularization in the
      treatment of acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate safety and
      efficacy of the Solitaire FR device in the treatment of patients with acute
      ischemic stroke secondary to large artery occlusion. METHODS: We conducted a
      retrospective study of consecutive patients presenting with acute ischemic stroke
      treated with Solitaire FR as the first-line device to restore blood flow in 6
      experienced European centers. This study was entirely funded and supported by
      Coviden Neurovascular. An independent Corelab determined modified Thrombolysis in
      Cerebral Infarction scores on the preprocedure and postprocedure angiograms.
      Complete revascularization was defined as modified Thrombolysis in Cerebral
      Infarction 2b or 3 post-Solitaire FR device use. Symptomatic intracranial
      hemorrhage was defined as parenchymal hemorrhage Type 2 associated with a decline
      of >= 4 points in the National Institutes of Health Stroke Scale score within 24
      hours or causing death. Favorable functional outcome was considered as modified
      Rankin Scale score <= 2 at Day 90. RESULTS: We studied 141 patients (mean age, 66
      years; median National Institutes of Health Stroke Scale, 18); 74 patients
      received intravenous tissue-type plasminogen activator before endovascular
      treatment. Complete revascularization was achieved in 120 of 142 occlusion sites
      (85%) and good outcome in 77 of 141 (55%) patients. Good outcome was more
      frequent in patients treated with intravenous tissue-type plasminogen activator
      than in those without (66% versus 42%; P<0.01). Symptomatic intracranial
      hemorrhage was reported in 5 patients (4%) and 29 of 141 (20%) patients died or
      were lost during follow-up (3 cases). CONCLUSIONS: This retrospective study with
      centralized evaluation shows that the use of Solitaire FR is safe and achieves
      good revascularization rates and functional outcomes in patients with acute
      ischemic stroke and large artery occlusion.

PMID- 22851548
TI  - Incidence of new diffusion-weighted imaging lesions outside the area of initial
      hypoperfusion within 1 week after acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: New diffusion-weighted imaging (DWI) lesions are common
      in patients with acute ischemic stroke. The pathophysiology of these new lesions
      is unclear. We differentiated new DWI lesions outside the area of initial
      hypoperfusion from those confined to the area of initial hypoperfusion. METHODS:
      Patients with acute stroke underwent 3 MRI examinations: on admission, on the
      next day, and 4 to 7 days after symptom onset. Patients were included if a
      perfusion deficit was present on the initial scan. Lesions on DWI images were
      delineated manually. Coregistered DWI images were analyzed visually for new
      hyperintensities. In reference to the perfusion maps (mean transit time),
      patients were classified as having "outside lesions" if new DWI lesions were
      outside or both outside and inside the area of the initial perfusion deficit or
      "inside lesions" if new DWI lesions were completely inside. RESULTS: We enrolled
      164 patients. Thirty-eight patients (23%) had outside lesions and 34 patients
      (21%) had inside lesions. In multivariable regression analysis, new outside
      lesions were significantly associated with symptomatic carotid stenosis, multiple
      index lesions pattern, and high low-density lipoprotein levels. New inside
      lesions were significantly associated with (spontaneous or thrombolytic) vessel
      recanalization, multiple index lesions pattern, and low low-density lipoprotein
      levels. CONCLUSIONS: Outside and inside lesions represent different
      pathophysiological entities. More specifically patients with outside lesions may
      have an increased risk for subsequent cerebrovascular events.

PMID- 22851549
TI  - Prevalence and predictors of 6-month fatigue in patients with ischemic stroke: a
      population-based stroke incidence study in Auckland, New Zealand, 2002-2003.
AB  - BACKGROUND AND PURPOSE: Although persistent and significant fatigue affects the
      daily life of stroke survivors, there are no population-based studies examining
      the prevalence of fatigue in 6-month survivors of ischemic stroke and few studies
      of predictors of poststroke fatigue. METHODS: This article examined data from the
      Auckland Regional Community Stroke study conducted in Auckland, New Zealand, in
      2002 to 2003. Presence of fatigue was evaluated at 6 months in 613 patients with
      ischemic stroke using a Short Form 36 Vitality Score (energy and fatigue) of <=
      47. Multivariate logistic regression analysis was used to determine predictors of
      fatigue development 6 months poststroke. RESULTS: The prevalence of fatigue was
      30% (28% in men and 33% in women). There was a clear association between
      increased prevalence of fatigue and advancing age. The only baseline variables
      independently associated with an increased risk of developing fatigue at 6 months
      poststroke were prestroke incontinence and being of New Zealand European
      ethnicity. Being independent and living alone at baseline were associated with
      significant reduction in the risk of being fatigued at 6 months poststroke.
      Severe depression at 6 months was significantly and independently associated with
      being fatigued. CONCLUSIONS: The prevalence of fatigue found in our study is at
      the lower level of range reported in other studies. The prevalence of fatigue
      increased with advancing age, as found in most previous studies. Because fatigue
      can have a negative impact on stroke recovery, particular attention needs to be
      paid to those who are older, incontinent before stroke, and those who report
      severe symptoms of depression at 6 months after stroke.

PMID- 22851550
TI  - The evolutionary root of flowering plants.
AB  - Correct rooting of the angiosperm radiation is both challenging and necessary for
      understanding the origins and evolution of physiological and phenotypic traits in
      flowering plants. The problem is known to be difficult due to the large genetic
      distance separating flowering plants from other seed plants and the sparse taxon
      sampling among basal angiosperms. Here, we provide further evidence for concern
      over substitution model misspecification in analyses of chloroplast DNA
      sequences. We show that support for Amborella as the sole representative of the
      most basal angiosperm lineage is founded on sequence site patterns poorly
      described by time-reversible substitution models. Improving the fit between
      sequence data and substitution model identifies Trithuria, Nymphaeaceae, and
      Amborella as surviving relatives of the most basal lineage of flowering plants.
      This finding indicates that aquatic and herbaceous species dominate the earliest
      extant lineage of flowering plants. [; ; ; ; ; .].

PMID- 22851552
TI  - Oak loss increases foliar nitrogen, delta(15)N and growth rates of Betula lenta
      in a northern temperate deciduous forest.
AB  - Oak forests dominate much of the eastern USA, but their future is uncertain due
      to a number of threats and widespread failure of oak regeneration. A sudden loss
      of oaks (Quercus spp.) could be accompanied by major changes in forest nitrogen
      (N) cycles with important implications for plant nutrient uptake and tree species
      composition. In this study, we measured the changes in N use and growth rates of
      black birch trees (Betula lenta L.) following oak girdling at the Black Rock
      Forest in southeastern New York, USA. Data were collected from nine experimental
      plots composed of three treatments: 100% oaks girdled (OG), 50% oaks girdled
      (O50) and control (C). Foliar N concentration and foliar (15)N abundance
      increased significantly in the oak-girdled plots relative to the control,
      indicating that the loss of oaks significantly altered N cycling dynamics. As
      mineralization and nitrification rates increase following oak loss, black birch
      trees increase N absorption as indicated by higher foliar N content and increased
      growth rates. Foliar N concentration increased by 15.5% in the O50 and 30.6% in
      the OG plots relative to the control, while O50 and OG plots were enriched in
      (15)N by 1.080/00 and 3.330/00, respectively (P < 0.0001). A 641% increase in
      black birch growth rates in OG plots suggests that this species is able to
      respond to additional N availability and/or increased light availability. The
      loss of oaks and subsequent increase in black birch productivity may have a
      lasting impact on ecosystem form and function.

PMID- 22851551
TI  - The utility of hedgehog signaling pathway inhibition for cancer.
AB  - The Hedgehog (Hh) signaling pathway has been implicated in tumor initiation and
      metastasis across different malignancies. Major mechanisms by which the Hh
      pathway is aberrantly activated can be attributed to mutations of members of Hh
      pathway or excessive/inappropriate expression of Hh pathway ligands. The Hh
      signaling pathway also affects the regulation of cancer stem cells, leading to
      their capabilities in tumor formation, disease progression, and metastasis.
      Preliminary results of early phase clinical trials of Hh inhibitors administered
      as monotherapy demonstrated promising results in patients with basal cell
      carcinoma and medulloblastoma, but clinically meaningful anticancer efficacy
      across other tumor types seems to be lacking. Additionally, cases of resistance
      have been already observed. Mutations of SMO, activation of Hh pathway components
      downstream to SMO, and upregulation of alternative signaling pathways are
      possible mechanisms of resistance development. Determination of effective Hh
      inhibitor-based combination regimens and development of correlative biomarkers
      relevant to this pathway should remain as clear priorities for future research.

PMID- 22851553
TI  - Does concordance between survey responses and administrative records differ by
      ethnicity for prescription medication?
AB  - BACKGROUND: Self-reported prescription medication use data is often used to
      measure differences across ethnic groups, but its accuracy may differ across
      ethnic groups. OBJECTIVE: We compared ethnic groups' self-reported medication use
      to their administrative records for respondents with diabetes, hypertension, and
      asthma. METHODS: We linked the Canadian Community Health Survey to administrative
      prescription drug records for 17,191 respondents in British Columbia, Canada. We
      evaluated the concordance between self-reported medication use and prescription
      drug records using positive predictive value, negative predictive value,
      sensitivity, specificity, and kappa statistic for self-identified Whites,
      Chinese, South Asians, and Southeast Asians/Filipinos. The concordance was
      calculated using prescription drug records as the reference standard. We also
      estimated the odds of disagreement (either a false positive or negative) in
      medication use with logistic regressions for each ethnic group, and compared them
      using the Blinder-Oaxaca method. RESULTS: We found that Chinese had the worst
      positive predictive value for asthma medication use at 0.41, while South Asians
      had the worst sensitivity for hypertension medication use at 0.60. The difference
      in reporting an error between ethnic groups was likely explained by differences
      in respondent characteristics. Particularly, if White respondents had the same
      characteristics as South Asians, then White respondents would have had 1.031 (95%
      CI: 1.020-1.041) higher odds of disagreement for hypertension medication use than
      with their own characteristics. CONCLUSION: Self-reported medication use may be a
      valid measure of ethnic groups' medication use if ethnic differences in
      characteristics, like household income are held constant. However, an important
      determinant of validity for all ethnic groups is whether medications are used
      routinely, or for a specific episode.

PMID- 22851554
TI  - Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in
      older patients with acute myeloid leukemia.
AB  - PURPOSE: There has been little survival improvement in older patients with acute
      myeloid leukemia (AML) in the last two decades. Improving induction treatment may
      improve the rate and quality of remission and consequently survival. In our
      previous trial, in younger patients, we showed improved survival for the majority
      of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy.
      PATIENTS AND METHODS: Untreated patients with AML or high-risk myelodysplastic
      syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to
      receive induction chemotherapy with either daunorubicin/ara-C or
      daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m(2) on day
      1 of course one of therapy. The primary end point was overall survival (OS).
      RESULTS: The overall response rate was 69% (complete remission [CR], 60%; CR with
      incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO
      (68%) arms. There was no difference in 30- or 60-day mortality and no major
      increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to
      54.6 months), 3-year cumulative incidence of relapse was significantly lower with
      GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3
      year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to
      1.00; P = .05). The benefit was apparent across subgroups. There was no
      interaction with other treatment interventions. A meta-analysis of 2,228 patients
      in two United Kingdom National Cancer Research Institute trials showed
      significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002)
      and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02). CONCLUSION: Adding GO (3
      mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival
      with little increase in toxicity.

PMID- 22851555
TI  - Can we really use retrospective subset analyses and surveillance, epidemiology,
      and end results data to drive clinical practice?

PMID- 22851556
TI  - Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG
      T-01.
AB  - PURPOSE: Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to
      conventional therapy. To evaluate the efficacy of a dose-dense approach
      consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell
      transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large
      prospective phase II study in untreated systemic PTCL. This is the final report,
      with a 5-year median follow-up, of the NLG-T-01 study. PATIENTS AND METHODS:
      Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were
      included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell
      lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly
      CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was
      administered (in patients age > 60 years, etoposide was omitted). If in complete
      or partial remission, patients proceeded to consolidation with HDT/ASCT. RESULTS:
      Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The
      majority presented with advanced-stage disease, B symptoms, and elevated serum
      lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete
      remission at 3 months post-transplantation. Early failures occurred in 26%.
      Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83
      patients were alive. Consolidated 5-year overall and progression-free survival
      (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively.
      Best results were obtained in ALK-negative ALCL. CONCLUSION: Dose-dense induction
      followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of
      treatment-naive patients with PTCL. This represents an encouraging outcome,
      particularly considering the high median age and adverse risk profile of the
      study population. Therefore, dose-dense induction and HDT/ASCT are a rational up
      front strategy in transplantation-eligible patients with PTCL.

PMID- 22851557
TI  - Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in
      untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499.
AB  - PURPOSE: To test the hypothesis that consolidation therapy with yttrium-90
      ((90)Y) -ibritumomab tiuxetan after brief initial therapy with four cycles of
      rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R
      CHOP) in patients with previously untreated mantle-cell lymphoma would be a well
      tolerated regimen that would improve outcomes compared with historical R-CHOP
      data. PATIENTS AND METHODS: Patients >= 18 years old with histologically
      confirmed mantle-cell lymphoma expressing CD20 and cyclin D1 who had not received
      any previous therapy and had an Eastern Cooperative Oncology Group performance
      status of 0 to 2 and adequate organ function were eligible. The study enrolled
      and treated 57 patients, of whom 56 patients were eligible. Fifty-two patients
      (50 eligible patients) received (90)Y-ibritumomab tiuxetan. The study design
      required 52 eligible patients to detect a 50% improvement in the median time to
      treatment failure (TTF) compared with that reported for six cycles of R-CHOP.
      RESULTS: With 56 analyzed patients (median age, 60 years; men, 73%), the overall
      response rate was 82% (55% complete response/complete response-unconfirmed). With
      a median follow-up of 72 months, the median TTF was 34.2 months. The median
      overall survival (OS) has not been reached, with an estimated 5-year OS of 73%
      (79% for patients <= age 65 years v 62% for patients > age 65 years; P = .08 [log
      rank test]). There were no unexpected toxicities. CONCLUSION: R-CHOP given for
      four cycles followed by (90)Y-ibritumomab tiuxetan compared favorably with
      historical results with six cycles of R-CHOP in patients with previously
      untreated mantle-cell lymphoma. This regimen was well tolerated and should be
      applicable to most patients with this disease.

PMID- 22851559
TI  - Fatalities resulting from accidental intrathecal administration of bortezomib:
      strategies for prevention.

PMID- 22851558
TI  - Randomized trial of radiation therapy plus procarbazine, lomustine, and
      vincristine chemotherapy for supratentorial adult low-grade glioma: initial
      results of RTOG 9802.
AB  - PURPOSE: A prior Radiation Therapy Oncology Group (RTOG) clinical trial in
      anaplastic oligodendroglioma suggested a progression-free survival benefit for
      procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to
      radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).
      PATIENTS AND METHODS: Eligibility criteria included supratentorial WHO grade 2
      LGG, age 18 to 39 years with subtotal resection/biopsy, or age >= 40 years with
      any extent resection. Patients were randomly assigned to RT alone or RT followed
      by six cycles of PCV. Survival was compared by using the modified Wilcoxon and
      log-rank tests. RESULTS: In all, 251 patients were accrued from 1998 to 2002.
      Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were
      7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR];
      0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free
      survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years
      versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to
      0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients
      between years 0 and 2. After 2 years, OS and PFS curves separated significantly,
      favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an
      additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95%
      CI, 0.30 to 0.90; log-rank P = .02). CONCLUSION: PFS but not OS was improved for
      adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis,
      for 2-year survivors, the addition of PCV to RT conferred a survival advantage,
      suggesting a delayed benefit for chemotherapy.

PMID- 22851560
TI  - Carboplatin dosing in infants with retinoblastoma: a case for therapeutic drug
      monitoring.

PMID- 22851562
TI  - Preventing human papillomavirus disease.

PMID- 22851561
TI  - Hyperfractionated versus conventional radiotherapy followed by chemotherapy in
      standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP
      PNET 4 trial.
AB  - PURPOSE: To compare event-free survival (EFS), overall survival (OS), pattern of
      relapse, and hearing loss in children with standard-risk medulloblastoma treated
      by postoperative hyperfractionated or conventionally fractionated radiotherapy
      followed by maintenance chemotherapy. PATIENTS AND METHODS: In all, 340 children
      age 4 to 21 years from 122 European centers were postoperatively staged and
      randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or
      standard (conventional) fractionated radiotherapy (STRT) followed by a common
      chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and
      vincristine. RESULTS: After a median follow-up of 4.8 years (range, 0.1 to 8.3
      years), survival rates were not significantly different between the two treatment
      arms: 5-year EFS was 77% +/- 4% in the STRT group and 78% +/- 4% in the HFRT
      group; corresponding 5-year OS was 87% +/- 3% and 85% +/- 3%, respectively. A
      postoperative residual tumor of more than 1.5 cm(2) was the strongest negative
      prognostic factor. EFS of children with all reference assessments and no large
      residual tumor was 82% +/- 2% at 5 years. Patients with a delay of more than 7
      weeks to the start of RT had a worse prognosis. Severe hearing loss was not
      significantly different for the two treatment arms at follow-up. CONCLUSION: In
      this large randomized European study, which enrolled patients with standard-risk
      medulloblastoma from more than 100 centers, excellent survival rates were
      achieved in patients without a large postoperative residual tumor and without RT
      treatment delays. EFS and OS for HFRT was not superior to STRT, which therefore
      remains standard of care in this disease.

PMID- 22851563
TI  - IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and
      adults with acute lymphoblastic leukemia.
AB  - PURPOSE: To determine the prevalence and prognostic impact of significant acute
      lymphoblastic leukemia (ALL) -related genes: CRLF2 deregulation (CRLF2-d), IGH@
      translocations (IGH@-t), and deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1,
      and EBF1 in adolescents and adults. PATIENTS AND METHODS: The cohort comprised
      454 patients (age 15 to 60 years old) treated on the multicenter United Kingdom
      Acute Lymphoblastic Leukaemia Trial XII/Eastern Cooperative Oncology Group 2993
      trial (UKALLXII/ECOG2993) with Philadelphia-negative B-cell precursor ALL.
      Fluorescent in situ hybridization and multiplex ligation-dependent probe
      amplification were used to detect these genetic alterations. RESULTS: Twenty
      patients (5%) had CRLF2-d (P2RY8-CRLF2, n = 7; IGH@-CRLF2, n = 13), and 36
      patients (8%) harbored an IGH@-t with a different partner gene. There was little
      overlap between IGH@-t, CRLF2-d, and established chromosomal abnormalities.
      Deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, or EBF1 were prevalent with
      101 (33%) of 304 patients harboring one and 102 (33%) harboring two or more
      alterations, occurring with varying frequency in all cytogenetic subgroups. The 5
      year event-free survival, relapse-free survival (RFS), and overall survival (OS)
      rates for the whole cohort were 40%, 55%, and 43%, respectively. Patients with
      CRLF2-d, IGH@-t, and IKZF1 deletions were associated with an inferior outcome in
      univariate but not multivariate analysis. In particular, CRLF2-d patients had a
      lower RFS compared with other patients (30%), whereas those with IGH@-t or IKZF1
      deletions had a lower OS (27% and 35%, respectively). CONCLUSION: CRLF2-d and
      IGH@-t represent distinct subtypes of adolescent and adult ALL. Deletions of key
      B-cell differentiation and cell cycle control genes are highly prevalent but vary
      in frequency by cytogenetic subgroup. CRLF2-d, IGH@-t, and IKZF1 deletions are
      associated with poor outcome in adolescent and adult ALL.

PMID- 22851564
TI  - Phase III, randomized, double-blind, placebo-controlled trial of
      gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of
      advanced, nonsquamous non-small-cell lung cancer.
AB  - PURPOSE: This trial evaluated the efficacy and safety of sorafenib plus
      gemcitabine/cisplatin in chemotherapy-naive patients with unresectable stage IIIB
      to IV nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Between February 2007 and March 2009, 904 patients were randomly assigned to
      daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1,250
      mg/m(2) per day on days 1 and 8) and cisplatin (75 mg/m(2) on day 1) for up to
      six 21-day cycles. Because of safety findings from the Evaluation of Sorafenib,
      Carboplatin and Paclitaxel Efficacy in NSCLC (ESCAPE) trial, patients with
      squamous cell histology were withdrawn from the trial in February 2008 and
      excluded from analysis. The primary end point was overall survival (OS), and
      secondary end points included progression-free survival (PFS) and time-to
      progression (TTP). RESULTS: The primary analysis population consisted of 772
      patients (sorafenib, 385; placebo, 387); the two groups had similar demographic
      and baseline characteristics. Median OS was similar in the sorafenib and placebo
      groups (12.4 v 12.5 months; hazard ratio [HR], 0.98; P = .401). By investigator
      assessment, sorafenib improved median PFS (6.0 v 5.5 months; HR, 0.83; P = .008)
      and TTP (6.1 v 5.5 months; HR, 0.73; P < .001). Grade 3 to 4 drug-related adverse
      events more than two-fold higher in the sorafenib group included hand-foot skin
      reaction (8.6% v 0.3%), fatigue (7.3% v 3.6%), rash (5.7% v 0.5%), and
      hypertension (4.2% v 1.8%). No unexpected toxicities were observed. CONCLUSION:
      This study did not meet its primary end point of improved OS when sorafenib was
      added to first-line gemcitabine/cisplatin in patients with advanced nonsquamous
      NSCLC. Identification of predictive biomarkers is warranted in future trials of
      sorafenib.

PMID- 22851565
TI  - Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated
      with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
AB  - PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients
      treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations,
      have been associated with inferior survival in DLBCL. We investigated whether
      expression of MYC protein, with or without BCL2 protein expression, could risk
      stratify patients at diagnosis. PATIENTS AND METHODS: We determined the
      correlation between presence of MYC and BCL2 proteins by immunohistochemistry
      (IHC) with survival in two independent cohorts of patients with DLBCL treated
      with R-CHOP. We further determined if MYC protein expression correlated with high
      MYC mRNA and/or presence of MYC translocation. RESULTS: In the training cohort (n
      = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients,
      respectively. Concurrent expression (MYC positive/BCL2 positive) was present in
      21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC
      translocation (both P < .001), but the latter was less frequent (both 11%). MYC
      protein expression was only associated with inferior overall and progression-free
      survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor
      prognostic effect of MYC positive/BCL2 positive was validated in an independent
      cohort of 140 patients with DLBCL and remained significant (P < .05) after
      adjusting for presence of high-risk features in a multivariable model that
      included elevated international prognostic index score, activated B-cell
      molecular subtype, and presence of concurrent MYC and BCL2 translocations.
      CONCLUSION: Assessment of MYC and BCL2 expression by IHC represents a robust,
      rapid, and inexpensive approach to risk-stratify patients with DLBCL at
      diagnosis.

PMID- 22851567
TI  - Dramatic response to trastuzumab and paclitaxel in a patient with human epidermal
      growth factor receptor 2-positive metastatic cholangiocarcinoma.

PMID- 22851566
TI  - Neuropathy is not associated with clinical outcomes in patients receiving
      adjuvant taxane-containing therapy for operable breast cancer.
AB  - PURPOSE: Neuropathy is a common and potentially disabling complication of
      adjuvant taxane therapy. Recent studies have identified candidate single
      nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we
      sought to determine whether neuropathy was associated with breast cancer
      recurrence in a clinical trial population who received adjuvant taxane therapy.
      PATIENTS AND METHODS: Trial E1199 included 4,554 eligible women with operable
      breast cancer who received up to four cycles of doxorubicin and cyclophosphamide
      every 3 weeks followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles
      (P3), paclitaxel 80 mg/m(2) weekly for 12 cycles (P1), docetaxel 100 mg/m(2)
      every 3 weeks for four cycles (D3), or docetaxel 35 mg/m(2) weekly for 12 cycles
      (D1). A Cox proportional hazards model was used to determine the relationship
      between neuropathy and disease-free survival (DFS), overall survival (OS), and
      recurrence-free survival (RFS) by treating neuropathy status as a time dependent
      covariate and using a landmark analysis. RESULTS: Of 4,554 patients who received
      at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and
      13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that
      included age, race, obesity, menopausal status, tumor size, nodal status,
      treatment arm, neuropathy, and hyperglycemia, no significant relationship was
      found between neuropathy and DFS, OS, or RFS. CONCLUSION: There was no
      association between taxane-induced neuropathy and outcome.

PMID- 22851569
TI  - Linking toxicity to the target.

PMID- 22851568
TI  - Induction chemotherapy and conformal radiation therapy for very young children
      with nonmetastatic medulloblastoma: Children's Oncology Group study P9934.
AB  - PURPOSE: P9934 was a prospective trial of systemic chemotherapy, second surgery,
      and conformal radiation therapy (CRT) limited to the posterior fossa and primary
      site for children between 8 months and 3 years old with nonmetastatic
      medulloblastoma. The study was open from June 2000 until June 2006. PATIENTS AND
      METHODS: After initial surgery, children received four cycles of induction
      chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa
      (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance
      chemotherapy. Neurodevelopmental outcomes were evaluated and event-free survival
      (EFS) results were directly compared with a previous study of multiagent
      chemotherapy without irradiation (Pediatric Oncology Group [POG] trial 9233).
      RESULTS: Seventy-four patients met eligibility requirements. The 4-year EFS and
      overall survival probabilities were 50% +/- 6% and 69% +/- 5.5%, respectively,
      which compared favorably to the results from POG 9233. Analysis showed that the
      desmoplastic/nodular subtype was a favorable factor in predicting survival. Our 4
      year EFS rate was 58% +/- 8% for patients with desmoplasia. Whereas seven of 10
      patients who had disease progression before CRT had primary-site failure, 15 of
      19 patients who progressed after CRT had distant-site failure. Neurodevelopmental
      assessments did not show a decline in cognitive or motor function after protocol
      directed chemotherapy and CRT. CONCLUSION: The addition of CRT to postoperative
      chemotherapy in young children with nonmetastatic medulloblastoma increased event
      free survival compared with the use of postoperative chemotherapy alone. Future
      studies will use histopathologic typing (desmoplastic/nodular versus
      nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.

PMID- 22851571
TI  - Multidisciplinary care and pursuit of active surveillance in low-risk prostate
      cancer.
AB  - PURPOSE: Multidisciplinary clinics offer a unique approach to the management of
      patients with cancer. Yet, limited data exist to show that such clinics affect
      management. The purpose of this study was to determine whether consultation at a
      multidisciplinary clinic is associated with selection of active surveillance in
      patients with low-risk prostate cancer. PATIENTS AND METHODS: The study comprised
      701 men with low-risk prostate cancer managed at three tertiary care centers in
      Boston, MA in 2009. Patients either obtained consultation at a multidisciplinary
      prostate cancer clinic, at which they were seen by a combination of urologic,
      radiation, and medical oncologists in a concurrent setting, or they were seen by
      individual practitioners in sequential settings. The primary outcome was
      selection of active surveillance. RESULTS: Crude rates of selection of active
      surveillance in patients seen at a multidisciplinary clinic were double that of
      patients seen by individual practitioners (43% v 22%), whereas the proportion of
      men treated with prostatectomy or radiation decreased by approximately 30% (P <
      .001). On multivariate logistic regression, older age (odds ratio [OR], 1.09; 95%
      CI, 1.05 to 1.12; P < .001), unmarried status (OR, 1.66; 95% CI, 1.01 to 2.72; P
      = .04), increased Charlson comorbidity index (OR, 1.37; 95% CI, 1.06 to 1.77; P =
      .02), fewer positive cores (OR, 0.92; 95% CI, 0.90 to 0.94; P < .001), and
      consultation at a multidisciplinary clinic (OR, 2.15; 95% CI, 1.13 to 4.10; P =
      .02) were significantly associated with pursuit of active surveillance.
      CONCLUSION: Multidisciplinary care is associated with increased selection of
      active surveillance in men with low-risk prostate cancer. This finding may have
      an important clinical, social, and economic impact.

PMID- 22851570
TI  - Clinical human papillomavirus detection forecasts cervical cancer risk in women
      over 18 years of follow-up.
AB  - PURPOSE: To describe the long-term (>= 10 years) benefits of clinical human
      papillomavirus (HPV) DNA testing for cervical precancer and cancer risk
      prediction. METHODS: Cervicovaginal lavages collected from 19,512 women attending
      a health maintenance program were retrospectively tested for HPV using a clinical
      test. HPV positives were tested for HPV16 and HPV18 individually using a research
      test. A Papanicolaou (Pap) result classified as atypical squamous cells of
      undetermined significance (ASC-US) or more severe was considered abnormal. Women
      underwent follow-up prospectively with routine annual Pap testing up to 18 years.
      Cumulative incidence rates (CIRs) of >= grade 3 cervical intraepithelial
      neoplasia (CIN3+) or cancer for enrollment test results were calculated. RESULTS:
      A baseline negative HPV test provided greater reassurance against CIN3+ over the
      18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline
      Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of
      follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years
      later (P = .004). HPV16- and HPV18-positive women with normal Pap were at
      elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and
      were at similar risk of CIN3+ compared with women with a low-grade squamous
      intraepithelial Pap. CONCLUSION: HPV testing to rule out cervical disease
      followed by Pap testing and possibly combined with the detection of HPV16 and
      HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be
      an efficient algorithm for cervical cancer screening, especially in women age 30
      years or older.

PMID- 22851572
TI  - Improvements in the life expectancy of type 1 diabetes: the Pittsburgh
      Epidemiology of Diabetes Complications study cohort.
AB  - Survival in type 1 diabetes has improved, but the impact on life expectancy in
      the U.S. type 1 diabetes population is not well established. Our objective was to
      estimate the life expectancy of the Pittsburgh Epidemiology of Diabetes
      Complications (EDC) study cohort and quantify improvements by comparing two
      subcohorts based on year of diabetes diagnosis (1950-1964 [n = 390] vs. 1965-1980
      [n = 543]). The EDC study is a prospective cohort study of 933 participants with
      childhood-onset (aged <17 years) type 1 diabetes diagnosed at Children's Hospital
      of Pittsburgh from 1950 to 1980. Mortality ascertainment was censored 31 December
      2009. Abridged cohort life tables were constructed to calculate life expectancy.
      Death occurred in 237 (60.8%) of the 1950-1964 subcohort compared with 88 (16.2%)
      of the 1965-1980 subcohort. The life expectancy at birth for those diagnosed 1965
      1980 was ~15 years greater than participants diagnosed 1950-1964 (68.8 [95% CI
      64.7-72.8] vs. 53.4 [50.8-56.0] years, respectively) (P < 0.0001); this
      difference persisted regardless of sex or pubertal status at diagnosis. This
      improvement in life expectancy emphasizes the need for insurance companies to
      update analysis of the life expectancy of those with childhood-onset type 1
      diabetes because weighting of insurance premiums is based on outdated estimates.

PMID- 22851573
TI  - The role of microRNA-146a in the pathogenesis of the diabetic wound-healing
      impairment: correction with mesenchymal stem cell treatment.
AB  - The impairment in diabetic wound healing represents a significant clinical
      problem. Chronic inflammation is thought to play a central role in the
      pathogenesis of this impairment. We have previously shown that treatment of
      diabetic murine wounds with mesenchymal stem cells (MSCs) can improve healing,
      but the mechanisms are not completely defined. MicroRNA-146a (miR-146a) has been
      implicated in regulation of the immune and inflammatory responses. We
      hypothesized that abnormal miRNA-146a expression may contribute to the chronic
      inflammation. To test this hypothesis, we examined the expression of miRNA-146a
      and its target genes in diabetic and nondiabetic mice at baseline and after
      injury. MiR-146a expression was significantly downregulated in diabetic mouse
      wounds. Decreased miR-146a levels also closely correlated with increased gene
      expression of its proinflammatory target genes. Furthermore, the correction of
      the diabetic wound-healing impairment with MSC treatment was associated with a
      significant increase in the miR-146a expression level and decreased gene
      expression of its proinflammatory target genes. These results provide the first
      evidence that decreased expression of miR-146a in diabetic wounds in response to
      injury may, in part, be responsible for the abnormal inflammatory response seen
      in diabetic wounds and may contribute to wound-healing impairment.

PMID- 22851574
TI  - Increased inner ear susceptibility to noise injury in mice with streptozotocin
      induced diabetes.
AB  - We aimed to investigate the pathophysiology of diabetes-associated hearing
      impairment in type 1 diabetes using mice with streptozotocin-induced diabetes
      (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after
      induction of diabetes (five diabetic and five control animals per time point)
      using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four
      control) were exposed to loud noise (105 dB) 5 months after induction of
      diabetes. ABRs were measured before and after noise exposure. Cochlear blood
      flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were
      counted. Vessel endothelial cells were observed by CD31 immunostaining.
      Chronologic changes in the ABR threshold shift were not significantly different
      between the diabetic and control groups. However, vessel walls in the modiolus of
      the cochleae were significantly thicker in the diabetic group than the control
      group. Additionally, recovery from noise-induced injury was significantly
      impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed
      in diabetic mice cochleae after noise exposure. Our data suggest that diabetic
      cochleae are more susceptible than controls to loud noise exposure, and decreased
      cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs
      are possible mechanisms of hearing impairment in diabetic patients.

PMID- 22851575
TI  - Dendritic cells promote macrophage infiltration and comprise a substantial
      proportion of obesity-associated increases in CD11c+ cells in adipose tissue and
      liver.
AB  - Obesity-associated increases in adipose tissue (AT) CD11c(+) cells suggest that
      dendritic cells (DC), which are involved in the tissue recruitment and activation
      of macrophages, may play a role in determining AT and liver immunophenotype in
      obesity. This study addressed this hypothesis. With the use of flow cytometry,
      electron microscopy, and loss-and-gain of function approaches, the contribution
      of DC to the pattern of immune cell alterations and recruitment in obesity was
      assessed. In AT and liver there was a substantial, high-fat diet (HFD)-induced
      increase in DC. In AT, these increases were associated with crown-like
      structures, whereas in liver the increase in DC constituted an early and
      reversible response to diet. Notably, mice lacking DC had reduced AT and liver
      macrophages, whereas DC replacement in DC-null mice increased liver and AT
      macrophage populations. Furthermore, delivery of bone marrow-derived DC to lean
      wild-type mice increased AT and liver macrophage infiltration. Finally, mice
      lacking DC were resistant to the weight gain and metabolic abnormalities of an
      HFD. Together, these data demonstrate that DC are elevated in obesity, promote
      macrophage infiltration of AT and liver, contribute to the determination of
      tissue immunophenotype, and play a role in systemic metabolic responses to an
      HFD.

PMID- 22851576
TI  - Short-term caloric restriction normalizes hypothalamic neuronal responsiveness to
      glucose ingestion in patients with type 2 diabetes.
AB  - The hypothalamus is critically involved in the regulation of feeding. Previous
      studies have shown that glucose ingestion inhibits hypothalamic neuronal
      activity. However, this was not observed in patients with type 2 diabetes.
      Restoring energy balance by reducing caloric intake and losing weight are
      important therapeutic strategies in patients with type 2 diabetes. We
      hypothesized that caloric restriction would have beneficial effects on the
      hypothalamic neuronal response to glucose ingestion. Functional magnetic
      resonance imaging was performed in 10 male type 2 diabetic patients before and
      after a 4-day very-low-calorie diet (VLCD) at a 3.0 Tesla scanner using a blood
      oxygen level-dependent technique for measuring neuronal activity in the
      hypothalamus in response to an oral glucose load. Hypothalamic signals were
      normalized to baseline value, and differences between the pre- and postdiet
      condition were tested using paired t tests. Pre-VLCD scans showed no response of
      the hypothalamus to glucose intake (i.e., no signal decrease after glucose intake
      was observed). Post-VLCD scans showed a prolonged signal decrease after glucose
      ingestion. The results of the current study demonstrate that short-term caloric
      restriction readily normalizes hypothalamic responsiveness to glucose ingestion
      in patients with type 2 diabetes.

PMID- 22851579
TI  - Quality appraisal in systematic reviews of public health interventions: an
      empirical study on the impact of choice of tool on meta-analysis.
AB  - INTRODUCTION: Systematic reviews are a cornerstone of evidence-based public
      health. The method of appraising the quality of different intervention and
      observational study designs in such reviews remains an important challenge. This
      article examines the applicability of selected quality appraisal tools (QATs) and
      the impact of choice of tool on the meta-analysis of a published systematic
      review. METHODS: The authors selected a systematic review on the effectiveness of
      hand washing with soap in preventing diarrhoea, covering a range of
      epidemiological study designs. 6 QATs were used to assess 13 studies meeting
      their inclusion criteria; component sections/questions were coded numerically to
      derive a summary score between -1 (low quality) and +1 (high quality) for each
      QAT and study. Heterogeneity in study quality was evaluated graphically using
      traffic light schemes and spider charts. Random effects meta-analysis was
      undertaken for all studies; sensitivity analyses for each QAT included only those
      studies with a score of 0 or above. RESULTS: The authors found substantial
      heterogeneity in summary scores for a given study. Their main meta-analysis
      yielded an OR of 0.60 (95% CI 0.47 to 0.77) with most sensitivity analyses giving
      similar pooled effect sizes with wider CIs. DISCUSSION: The six QATs differ
      greatly in applicability across study designs, approach to quality appraisal (ie,
      scale vs checklist, presence/absence of summary score), coverage of domains and
      quality of component questions and answers. Learning from advantages and
      disadvantages of each QAT, we recommend research into the development of a
      reliable QAT with a broad applicability across study designs.

PMID- 22851577
TI  - Exercise alleviates lipid-induced insulin resistance in human skeletal muscle
      signaling interaction at the level of TBC1 domain family member 4.
AB  - Excess lipid availability causes insulin resistance. We examined the effect of
      acute exercise on lipid-induced insulin resistance and TBC1 domain family member
      1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male
      subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline
      or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp
      was performed. Femoral catheterization and analysis of biopsy specimens enabled
      measurements of leg substrate balance and muscle signaling. Each subject
      underwent two experimental trials, differing only by saline or intralipid
      infusion. Glucose infusion rate and leg glucose uptake was decreased by
      intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised
      leg in the saline and the lipid trials. In the lipid trial, prior exercise
      normalized insulin-stimulated glucose uptake to the level observed in the resting
      control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4.
      Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites
      compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation
      compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH)
      phosphorylation and lactate release. Prior exercise led to higher PDH
      phosphorylation and activation of glycogen synthase compared with resting
      control. In conclusion, lipid-induced insulin resistance in skeletal muscle was
      associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The
      prophylactic effect of exercise on lipid-induced insulin resistance may involve
      augmented TBC1D4 signaling and glycogen synthase activation.

PMID- 22851578
TI  - Depressed levels of prostaglandin F2alpha in mice lacking Akr1b7 increase basal
      adiposity and predispose to diet-induced obesity.
AB  - Negative regulators of white adipose tissue (WAT) expansion are poorly documented
      in vivo. Prostaglandin F(2alpha) (PGF(2alpha)) is a potent antiadipogenic factor
      in cultured preadipocytes, but evidence for its involvement in physiological
      context is lacking. We previously reported that Akr1b7, an aldo-keto reductase
      enriched in adipose stromal vascular fraction but absent from mature adipocytes,
      has antiadipogenic properties possibly supported by PGF(2alpha) synthase
      activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo,
      we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed
      excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and
      exhibited greater sensitivity to diet-induced obesity. Following adipose
      enlargement and irrespective of the diet, they developed liver steatosis and
      progressive insulin resistance. Akr1b7 loss was associated with decreased
      PGF(2alpha) WAT contents. Cloprostenol (PGF(2alpha) agonist) administration to
      Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte
      differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice
      with cloprostenol suggested that decreased adipocyte size resulted from
      inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of
      WAT development through at least two PGF(2alpha)-dependent mechanisms: inhibition
      of adipogenesis and lipogenesis. These findings provide molecular rationale to
      explore the status of aldo-keto reductases in dysregulations of adipose tissue
      homeostasis.

PMID- 22851580
TI  - Seven caveats on the use of low birthweight and related indicators in health
      research.
AB  - Birthweight and gestational age are the two most commonly used continuous
      variables in perinatal research. Dichotomous outcomes derived from these two
      variables include low birthweight, preterm birth and small for gestational age,
      each extensively used as perinatal and population health indicators within public
      health research and health surveillance systems. However, these dichotomous
      indicators have inherent limitations that need to be considered in the design,
      analysis and interpretation of epidemiological studies. In this report, we
      present seven caveats that may help researchers and users of epidemiological data
      avoid common (and not so common) pitfalls in the consideration of these
      indicators.

PMID- 22851581
TI  - Heparin prophylaxis has no benefit in medical patients.

PMID- 22851582
TI  - Doctors' performance. Patient reported measures are needed.

PMID- 22851583
TI  - The grand scheme of public disclosure?

PMID- 22851584
TI  - Good question, wrong answer.

PMID- 22851585
TI  - Doctors' performance. Don't blame individuals for organisational failures.

PMID- 22851586
TI  - Professional societies can lead the way on transparency but will need support.

PMID- 22851587
TI  - Time frames for radiography are unrealistic.

PMID- 22851588
TI  - Health warning--not all evidence based.

PMID- 22851589
TI  - No evidence on screening for cancer.

PMID- 22851591
TI  - NICE guideline has weaknesses.

PMID- 22851592
TI  - Collaboration between generalists in primary and secondary care is needed.

PMID- 22851593
TI  - Urgent referrals for suspected cancer vary threefold among general practices.

PMID- 22851594
TI  - Zinc finger transcription factor zDC is a negative regulator required to prevent
      activation of classical dendritic cells in the steady state.
AB  - Classical dendritic cells (cDCs) process and present antigens to T cells. Under
      steady-state conditions, antigen presentation by cDCs induces tolerance. In
      contrast, during infection or inflammation, cDCs become activated, express higher
      levels of cell surface MHC molecules, and induce strong adaptive immune
      responses. We recently identified a cDC-restricted zinc finger transcription
      factor, zDC (also known as Zbtb46 or Btbd4), that is not expressed by other
      immune cell populations, including plasmacytoid DCs, monocytes, or macrophages.
      We define the zDC consensus DNA binding motif and the genes regulated by zDC
      using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the
      mouse genome, we show that zDC is primarily a negative regulator of cDC gene
      expression. zDC deficiency alters the cDC subset composition in the spleen in
      favor of CD8(+) DCs, up-regulates activation pathways in steady-state cDCs,
      including elevated MHC II expression, and enhances cDC production of vascular
      endothelial growth factor leading to increased vascularization of skin-draining
      lymph nodes. Consistent with these observations, zDC protein expression is
      rapidly down-regulated after TLR stimulation. Thus, zDC is a TLR-responsive, cDC
      specific transcriptional repressor that is in part responsible for preventing cDC
      maturation in the steady state.

PMID- 22851596
TI  - Serum concentration of cystatin C and risk of end-stage renal disease in
      diabetes.
AB  - OBJECTIVE: Patients with diabetes have a high risk of end-stage renal disease
      (ESRD). We examined whether prediction of this outcome, according to chronic
      kidney disease (CKD) staging by creatinine-based estimates of the glomerular
      filtration rate (eGFRcreat), is improved by further staging with serum cystatin C
      based estimates (eGFRcyst). RESEARCH DESIGN AND METHODS: Patients with diabetes
      in CKD stages 1-3 were selected from three cohorts: two from Joslin Diabetes
      Center, one with type 1 diabetes (N = 364) and one with type 2 diabetes (N =
      402), and the third from the Finnish Diabetic Nephropathy (FinnDiane) Study of
      type 1 (N = 399). Baseline serum concentrations of creatinine and cystatin C were
      measured in all patients. Follow-up averaged 8-10 years and onsets of ESRD (n =
      246) and death unrelated to ESRD (n = 159) were ascertained. RESULTS: Although
      CKD staging by eGFRcyst was concordant with that by eGFRcreat for 62% of Joslin
      patients and 73% of FinnDiane patients, those given a higher stage by eGFRcyst
      than eGFRcreat had a significantly higher risk of ESRD than those with concordant
      staging in all three cohorts (hazard ratio 2.3 [95% CI 1.8-3.1]). Similarly,
      patients at a lower stage by eGFRcyst than by eGFRcreat had a lower risk than
      those with concordant staging (0.30 [0.13-0.68]). Deaths unrelated to ESRD
      followed the same pattern, but differences were not as large. CONCLUSIONS: In
      patients with diabetes, CKD staging based on eGFRcyst significantly improves ESRD
      risk stratification based on eGFRcreat. This conclusion can be generalized to
      patients with type 1 and type 2 diabetes and to diabetic patients in the U.S. and
      Finland.

PMID- 22851595
TI  - Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex
      encephalitis of childhood.
AB  - Childhood herpes simplex virus-1 (HSV-1) encephalitis (HSE) may result from
      single-gene inborn errors of TLR3 immunity. TLR3-dependent induction of IFN
      alpha/beta or IFN-lambda is crucial for protective immunity against primary HSV-1
      infection in the central nervous system (CNS). We describe here two unrelated
      children with HSE carrying different heterozygous mutations (D50A and G159A) in
      TBK1, the gene encoding TANK-binding kinase 1, a kinase at the crossroads of
      multiple IFN-inducing signaling pathways. Both mutant TBK1 alleles are loss-of
      function but through different mechanisms: protein instability (D50A) or a loss
      of kinase activity (G159A). Both are also associated with an autosomal-dominant
      (AD) trait but by different mechanisms: haplotype insufficiency (D50A) or
      negative dominance (G159A). A defect in polyinosinic-polycytidylic acid-induced
      TLR3 responses can be detected in fibroblasts heterozygous for G159A but not for
      D50A TBK1. Nevertheless, viral replication and cell death rates caused by two
      TLR3-dependent viruses (HSV-1 and vesicular stomatitis virus) were high in
      fibroblasts from both patients, and particularly so in G159A TBK1 fibroblasts.
      These phenotypes were rescued equally well by IFN-alpha2b. Moreover, the IFN
      responses to the TLR3-independent agonists and viruses tested were maintained in
      both patients' peripheral blood mononuclear cells and fibroblasts. The narrow,
      partial cellular phenotype thus accounts for the clinical phenotype of these
      patients being limited to HSE. These data identify AD partial TBK1 deficiency as
      a new genetic etiology of childhood HSE, indicating that TBK1 is essential for
      the TLR3- and IFN-dependent control of HSV-1 in the CNS.

PMID- 22851597
TI  - Skin intrinsic fluorescence is associated with coronary artery disease in
      individuals with long duration of type 1 diabetes.
AB  - OBJECTIVE: Skin intrinsic fluorescence (SIF) reflects many factors, including the
      presence of certain advanced glycation end products. We investigated whether SIF
      was associated with coronary artery disease (CAD) in type 1 diabetes and whether
      this relationship was independent of renal disease. RESEARCH DESIGN AND METHODS:
      SIF was measured in 112 subjects from the Pittsburgh Epidemiology of Diabetes
      Complications (EDC) study and 60 from MedStar Health Research Institute when mean
      age and diabetes duration were 48 and 36 years, respectively. Cumulative glycemic
      exposure (updated mean A1C) represented a mean of 18 years' follow-up in EDC and
      10.3 in MedStar. RESULTS: Of the 172 participants, 30 had CAD (15 male and 15
      female). SIF levels were higher in those with CAD (P < 0.0001). SIF was strongly
      associated with CAD (odds ratio [OR] 3.5 [95% CI 2.1-6.1]). After age, duration,
      and updated mean A1C were controlled for, SIF remained associated with CAD (2.4
      [1.3-4.4]), more strongly in men (5.6 [2.1-14.6]) than in women (1.4 [0.61-3.3]).
      As there was no significant sex interaction, further analyses were conducted
      combining the sexes. Further accounting for sex and nephropathy status did not
      improve the model fit, though with nephropathy in the model, the OR for SIF was
      reduced to 1.7 (95% CI 0.89-3.4). CONCLUSIONS: SIF has a significant cross
      sectional association with CAD. This association is strongly linked to age and
      duration and, to a lesser degree, to mean A1C and renal disease. SIF therefore
      may be a useful overall marker of CAD risk in type 1 diabetes.

PMID- 22851598
TI  - Maternal efficacy and safety outcomes in a randomized, controlled trial comparing
      insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes.
AB  - OBJECTIVE: This randomized, controlled noninferiority trial aimed to compare the
      efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn
      (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: Patients were randomized and exposed to IDet or NPH
      up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis
      aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36
      gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear
      regression, taking several baseline factors and covariates into account. RESULTS:
      A total of 310 type 1 diabetic women were randomized and exposed to IDet (n =
      152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy
      at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for
      NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, 
      0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting
      plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs
      (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017).
      Major and minor hypoglycemia rates during pregnancy were similar between groups.
      CONCLUSIONS: Treatment with IDet resulted in lower FPG and noninferior A1C in
      late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

PMID- 22851599
TI  - Intervention costs and cost-effectiveness of a successful telephonic intervention
      to promote diabetes control.
AB  - OBJECTIVE: To characterize the costs and cost-effectiveness of a telephonic
      behavioral intervention to promote glycemic control in the Improving Diabetes
      Outcomes study. RESEARCH DESIGN AND METHODS: Using the provider perspective and a
      time horizon to the end of the 1-year intervention, we calculate the costs of a
      telephonic intervention by health educators compared with an active control
      (print) intervention to improve glycemic control in adults with type 2 diabetes.
      We calculate the cost-effectiveness ratios for a reduction of one percentage
      point in hemoglobin A(1c) (A1C), as well as for one participant to achieve an A1C
      <7%. Base-case and sensitivity analysis results are presented. RESULTS: The
      intervention cost $176.61 per person randomized to the telephone group to achieve
      a mean 0.36 percentage point of A1C improvement. The incremental cost
      effectiveness ratio was $490.58 per incremental percentage point of A1C
      improvement and $2,617.35 per person over a 1-year intervention in achieving the
      A1C goal. In probabilistic sensitivity analysis, the median (interquartile range)
      of per capita cost, cost per percentage point reduction in A1C, and cost per
      person achieving the A1C goal of <7% are $175.82 (147.32-203.56), $487.75 (356.50
      718.32), and $2,312.88 (1,785.58-3,220.78), respectively. CONCLUSIONS: The costs
      of a telephonic intervention for diabetes self-management support are moderate
      and commensurate to the modest associated improvement in glycemic control.

PMID- 22851601
TI  - Romney lays down pro-life credentials with vow to ban most abortions.

PMID- 22851600
TI  - Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the
      human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with
      type 2 diabetes: a randomized, open-label trial.
AB  - OBJECTIVE: To assess the efficacy and safety of switching from sitagliptin to
      liraglutide in metformin-treated adults with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: In an open-label trial, participants randomized to receive either
      liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to
      metformin, continued treatment for 52 weeks. In a 26-week extension, sitagliptin
      treated participants were randomly allocated to receive instead liraglutide at
      either 1.2 or 1.8 mg/day, while participants originally randomized to receive
      liraglutide continued unchanged. RESULTS: Although 52 weeks of sitagliptin
      changed glycosylated hemoglobin (HbA(1c)) by -0.9% from baseline, additional
      decreases occurred after switching to liraglutide (1.2 mg/day, -0.2%, P = 0.006;
      1.8 mg/day, -0.5%, P = 0.0001). Conversion to liraglutide was associated with
      reductions in fasting plasma glucose (FPG) (1.2 mg/day, -0.8 mmol/L, P = 0.0004;
      1.8 mg/day, -1.4 mmol/L, P < 0.0001) and body weight (1.2 mg/day, -1.6 kg; 1.8
      mg/day, -2.5 kg; both P < 0.0001) and with an increased proportion of patients
      reaching HbA(1c) <7% (from ~30% to ~50%). Overall treatment satisfaction,
      assessed by the Diabetes Treatment Satisfaction Questionnaire, improved after
      switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P = 0.0189). After
      switching, mostly transient nausea occurred in 21% of participants, and minor
      hypoglycemia remained low (3-4% of participants). Continuing liraglutide
      treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks reduced HbA(1c) (baseline 8.3
      and 8.4%, respectively) by -0.9 and -1.3%, respectively; FPG by -1.3 and -1.7
      mmol/L, respectively; and weight by -2.6 and -3.1 kg, respectively, with 9-10% of
      participants reporting minor hypoglycemia. CONCLUSIONS: Glycemic control, weight,
      and treatment satisfaction improved after switching from sitagliptin to
      liraglutide, albeit with a transient increase in gastrointestinal reactions.

PMID- 22851602
TI  - Organ donors could be given priority for transplants under new rules.

PMID- 22851603
TI  - Alternative prion proteins.

PMID- 22851605
TI  - Comprehensive analysis of the TRPV4 gene in a large series of inherited
      neuropathies and controls.
AB  - BACKGROUND: TRPV4 mutations have been identified in Charcot-Marie-Tooth type 2
      (CMT2), scapuloperoneal spinal muscular atrophy and distal hereditary motor
      neuropathy (dHMN). OBJECTIVE: We aimed to screen the TRPV4 gene in 422 British
      patients with inherited neuropathy for potentially pathogenic mutations. METHODS:
      We sequenced TRPV4 coding regions and splice junctions in 271 patients with CMT2
      and 151 patients with dHMN. Mutations were clinically and genetically
      characterised and screened in >=345 matched controls. RESULTS: 13 missense and
      nonsense variants were identified, of which five were novel and absent from
      controls (G20R, E218K, N302Y, Y567X and T701I). N302Y and T701I mutations were
      present in typical CMT2 cases and are potentially pathogenic based on in silico
      analyses. G20R was detected in a patient with dHMN and her asymptomatic father
      and is possibly pathogenic with variable expressivity. The Y567X variant
      segregated with disease in a family with severe CMT2 but also with a MFN2
      mutation reported to cause a mild CMT2 phenotype. Although Y567X caused nonsense
      mediated mRNA decay, the amount of TRPV4 protein on western blotting of patient
      lymphoblasts was no different to control. Y567X is therefore unlikely to be
      pathogenic. E218K is unlikely to be pathogenic based on segregation. CONCLUSIONS:
      In this comprehensive analysis of the TRPV4 gene, we identified mutations in <1%
      of patients with CMT2/dHMN. We found that TRPV4 likely harbours many missense and
      nonsense non-pathogenic variants that should be analysed in detail to prove
      pathogenicity before results are given to patients.

PMID- 22851606
TI  - Beauty versus the beast.

PMID- 22851607
TI  - Cognitive and mood effects of phenobarbital treatment in people with epilepsy in
      rural China: a prospective study.
AB  - BACKGROUND: Phenobarbital is an effective treatment for epilepsy but concerns
      remain over its potential neurocognitive toxicity. This prospective study
      evaluated the effects of phenobarbital treatment on cognition and mood in people
      with epilepsy in rural China. METHODS: We recruited 144 adults with convulsive
      seizures and 144 healthy controls from six sites in rural China. People with
      epilepsy were treated with phenobarbital monotherapy for 12 months. At baseline,
      and at 3, 6 and 12 months, cases and controls were evaluated with a battery of
      neuropsychological tests: the Mini-Mental State Examination, the Hamilton
      Depression Rating Scale, a digit span test, a verbal fluency test, an auditory
      verbal learning test and a digit cancellation test. Efficacy of phenobarbital
      treatment was evaluated at the end of follow-up for those with epilepsy. RESULTS:
      Cognitive test scores and mood ratings were available for 136 (94%) people with
      epilepsy and 137 (95%) controls at the 12 month follow-up. Both groups showed
      slightly improved performance on a number of neuropsychological measures. The
      people with epilepsy showed greater performance gains (p=0.012) in verbal
      fluency. Nine people with epilepsy complained of memory problems during the
      treatment period. CONCLUSION: In this study, phenobarbital was not found to have
      a major negative impact on cognitive function of people with convulsive seizures
      and some cognitive gains were observed, possibly due to improved seizure control.

PMID- 22851608
TI  - Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis:
      epidemiological and clinical characteristics.
AB  - BACKGROUND: Information regarding the epidemiological background of Bickerstaff
      brainstem encephalitis (BBE) is limited. METHODS: We conducted a nationwide
      survey of BBE in the Japanese population in two steps: the first aimed to
      identify patients with brainstem encephalitis for the specified 3 year period and
      the second to evaluate whether the clinical picture met our diagnostic criteria
      for BBE. RESULTS: The number of patients with brainstem encephalitis was
      estimated as 704 (95% CI 478 to 930) over the 3 years. The annual onset of BBE
      was roughly estimated as 100 cases, which accounted for 43% of brainstem
      encephalitis. BBE was slightly male predominant and often young onset. Among
      brainstem encephalitis patients, BBE was characterised by antecedent infectious
      symptoms, oropharyngeal palsy and sensory disturbance at the distal extremities
      with absent or decreased tendon reflexes, in addition to a triad of symptoms
      (external ophthalmoplegia, ataxia and impaired level of consciousness) and
      shorter duration to the peak, with good outcome. Anti-GQ1b antibodies were
      present in 75% of cases. Several BBE patients with atypical clinical features or
      without anti-GQ1b antibodies were also identified. These cases often had marked
      CSF pleocytosis, abnormal brain MRI findings and a longer duration to peak
      symptoms, sometimes with considerable residual deficits. CONCLUSIONS: BBE is a
      rare disorder but accounts for a major proportion of brainstem encephalitis. BBE
      consists of typical and atypical cases. Typical BBE has similar neurological and
      serological features to Fisher syndrome and shows good recovery whereas atypical
      BBE is characterised by delayed recovery, negative anti-GQ1b antibodies, and
      abnormal CSF and brain MRI findings with other possible pathogeneses.

PMID- 22851609
TI  - QOLIBRI overall scale: a brief index of health-related quality of life after
      traumatic brain injury.
AB  - BACKGROUND: The quality of life after brain injury (QOLIBRI) scale is a recently
      developed instrument that provides a profile of health-related quality of life
      (HRQoL) in domains typically affected by brain injury. However, for global
      assessment it is desirable to have a brief summary measure. This study examined a
      6-item QOLIBRI overall scale (QOLIBRI-OS), and considered whether it could
      provide an index of HRQoL after traumatic brain injury (TBI). METHODS: The
      properties of the QOLIBRI-OS were studied in a sample of 792 participants with
      TBI recruited from centres in nine countries covering six languages. An
      examination of construct validity was undertaken on a subsample of 153
      participants recruited in Germany who had been assessed on two relevant brief
      quality of life measures, the satisfaction with life scale and the quality of
      life visual analogue scale. RESULTS: The reliability of the QOLIBRI-OS was good
      (Cronbach's alpha=0.86, test-retest reliability =0.81) and similar in
      participants with higher and lower cognitive performance. Factor analysis
      indicated that the scale is unidimensional. Rasch analysis also showed a
      satisfactory fit with this model. The QOLIBRI-OS correlates highly with the total
      score from the full QOLIBRI scale (r=0.87). Moderate to strong relationships were
      found among the QOLIBRI-OS and the extended glasgow outcome scale, short-form-36,
      and hospital anxiety and depression scale (r=0.54 to -0.76). The QOLIBRI-OS
      showed good construct validity in the TBI group. CONCLUSIONS: The QOLIBRI-OS
      assesses a similar construct to the QOLIBRI total score and can be used as a
      brief index of HRQoL for TBI.

PMID- 22851610
TI  - Neurological picture. Multiple intracranial abscesses due to Streptococcus
      anginosus in a previously well individual.

PMID- 22851611
TI  - Sniffing out the cerebellum.

PMID- 22851612
TI  - Evaluation of cognitive impairment by the Montreal cognitive assessment in
      patients with aneurysmal subarachnoid haemorrhage: prevalence, risk factors and
      correlations with 3 month outcomes.
AB  - OBJECTIVE: Identification of patients with aneurysmal subarachnoid haemorrhage
      (aSAH) with cognitive impairment is important for patient management (medical
      treatment, cognitive rehabilitation and social arrangements). The Montreal
      cognitive assessment (MoCA) is currently recommended over the mini-mental state
      examination (MMSE) by the U.S. National Institute of Neurological Disorder, in
      the chronic post-stroke setting. We hypothesised that the MoCA has a better
      correlation with functional outcome at 3 months than the MMSE. METHODS: We
      carried out a prospective observational study in Hong Kong over a 2 year period,
      recruiting patients aged 21-75 years with aSAH admitted within 96 h of ictus. The
      assessments included the modified Rankin Scale, Lawton Instrumental Activity of
      Daily Living (IADL), Short Form-36, MoCA and MMSE at 3 months after ictus.
      Analyses were carried out to compare MoCA with MMSE. RESULTS: 90 patients
      completed the 3 month assessments. Cognitive impairment (MoCA <26) was determined
      in 73% of patients at 3 months. Delayed cerebral infarction explained the 31-38%
      variance in cognitive outcomes (MMSE and MoCA) at 3 months. MoCA demonstrated
      good discrimination of favourable neurological and IADL outcomes similar to the
      MMSE in receiver operating characteristics curve analyses. CONCLUSIONS: MoCA
      defined cognitive impairment was common at 3 months after aSAH and MoCA
      correlated with functional outcomes similar, but not superior, to the MMSE. The
      study is registered at ClinicalTrials.gov of the US National Institutes of Health
      (NCT01038193).

PMID- 22851614
TI  - Oxidative ipso substitution of 2,4-difluoro-benzylphthalazines: identification of
      a rare stable quinone methide and subsequent GSH conjugate.
AB  - In vitro metabolite identification and GSH trapping studies in human liver
      microsomes were conducted to understand the bioactivation potential of compound 1
      [2-(6-(4-(4-(2,4-difluorobenzyl)phthalazin-1-yl)piperazin-1-yl)pyridin-3
      yl)propan-2-ol], an inhibitor of the Hedgehog pathway. The results revealed the
      formation of a unique, stable quinone methide metabolite (M1) via ipso
      substitution of a fluorine atom and subsequent formation of a GSH adduct (M2).
      The stability of this metabolite arises from extensive resonance-stabilized
      conjugation of the substituted benzylphthalazine moiety. Cytochrome P450 (P450)
      phenotyping studies revealed that the formation of M1 and M2 were NADPH-dependent
      and primarily catalyzed by CYP3A4 among the studied P450 isoforms. In summary, an
      unusual and stable quinone methide metabolite of compound 1 was identified, and a
      mechanism was proposed for its formation via an oxidative ipso substitution.

PMID- 22851613
TI  - An independent genome duplication inferred from Hox paralogs in the American
      paddlefish--a representative basal ray-finned fish and important comparative
      reference.
AB  - Vertebrates have experienced two rounds of whole-genome duplication (WGD) in the
      stem lineages of deep nodes within the group and a subsequent duplication event
      in the stem lineage of the teleosts-a highly diverse group of ray-finned fishes.
      Here, we present the first full Hox gene sequences for any member of the
      Acipenseriformes, the American paddlefish, and confirm that an independent WGD
      occurred in the paddlefish lineage, approximately 42 Ma based on sequences
      spanning the entire HoxA cluster and eight genes on the HoxD gene cluster. These
      clusters comprise different HOX loci and maintain conserved synteny relative to
      bichir, zebrafish, stickleback, and pufferfish, as well as human, mouse, and
      chick. We also provide a gene genealogy for the duplicated fzd8 gene in
      paddlefish and present evidence for the first Hox14 gene in any ray-finned fish.
      Taken together, these data demonstrate that the American paddlefish has an
      independently duplicated genome. Substitution patterns of the "alpha" paralogs on
      both the HoxA and HoxD gene clusters suggest transcriptional inactivation
      consistent with functional diploidization. Further, there are similarities in the
      pattern of sequence divergence among duplicated Hox genes in paddlefish and
      teleost lineages, even though they occurred independently approximately 200 Myr
      apart. We highlight implications on comparative analyses in the study of the "fin
      limb transition" as well as gene and genome duplication in bony fishes, which
      includes all ray-finned fishes as well as the lobe-finned fishes and tetrapod
      vertebrates.

PMID- 22851615
TI  - Characterization of THLE-cytochrome P450 (P450) cell lines: gene expression
      background and relationship to P450-enzyme activity.
AB  - The hepatic SV40 large T-antigen immortalized human liver epithelial (THLE) cell
      line and sublines transfected with cytochromes P450 (P450s) are increasingly
      being used for evaluation of potential drug-induced liver injury. So far, the
      available information on transporter and enzyme expression in these transfected
      cell systems is scattered. The purpose of this study was to characterize THLE
      cell lines with respect to transporter and enzyme expression. The mRNA expression
      of 96 typical drug absorption, distribution, metabolism and excretion genes,
      which encode a selection of transporters, phase I and II drug-metabolizing
      enzymes, and nuclear hormone receptors, was investigated in five THLE cell lines
      transfected with individual human P450s and in mock-transfected THLE-null cells
      using real-time polymerase chain reaction. The majority of the analyzed genes was
      either absent or expressed at low levels in the THLE-null and THLE-P450 cells,
      apart from housekeeping genes and the individual transfected P450s. Enzyme
      activity measurements provided confirmatory functional data for CYP2C9 and
      CYP3A4. Comparison with gene expression in human liver revealed an overall much
      lower gene expression in the THLE cell lines. The low levels of expression of a
      broad range of P450 genes in the THLE cell lines highlight the value of studies
      undertaken with P450-expressing cell lines for investigation of mechanisms of
      P450 metabolite-mediated hepatotoxicity. However, when attempting to translate
      between data obtained in THLE cell lines in vitro and functional consequences in
      vivo, it is important to take account of their limited expression of genes
      encoding many other drug-metabolizing enzymes and hepatic transporters.

PMID- 22851616
TI  - ATP serves as an endogenous inhibitor of UDP-glucuronosyltransferase (UGT): a new
      insight into the latency of UGT.
AB  - We have suggested that adenine-related compounds are allosteric inhibitors of UGT
      in rat liver microsomes (RLM) treated with detergent. To clarify whether the same
      occurs with a pore-forming peptide, alamethicin, the effects of adenine-related
      compounds on 4-metylumbelliferone (4-MU) glucuronidation were examined using RLM
      and human liver microsomes (HLM). ATP inhibited 4-MU glucuronidation when
      polyoxyethylene cetyl alcohol ether (Brij-58)-treated RLM were used (IC(50) =
      approximately 70 MUM). However, alamethicin-treated RLM exhibited a lower
      susceptibility (IC(50) = approximately 460 MUM) than Brij-58-treated RLM. A
      similar phenomenon was observed when pooled HLM were used. Then, the endogenous
      ATP content of RLM was determined in the presence and absence of alamethicin or
      detergent, and although no ATP remained in the microsomal pellets after Brij-58
      treatment, more than half of the microsomal ATP remained even after treatment
      with alamethicin. Furthermore, the V(max) in the absence of an adenine-related
      compound was approximately three times higher in Brij-58-treated than in
      alamethicin-treated RLM. The difference in the inhibitory potency observed was
      due to the difference in remaining endogenous ATP and the accessibility of
      exogenous ATP to the luminal side of the endoplasmic reticulum (ER), where the
      active site of UDP-glucuronosyltransferase (UGT) is located. Gefitinib (Iressa),
      a protein tyrosine kinase inhibitor, markedly inhibited human UGT1A9 activity. It
      is interesting to note that AMP antagonized Gefitinib-provoked inhibition of
      UGT1A9, and ATP exhibited an additive inhibitory effect at a lower concentration.
      Therefore, Gefitinib inhibits UGT1A9 at the common ATP-binding site shared with
      ATP and AMP. Releasing adenine nucleotide from the ER is suggested to be one of
      the mechanisms that explain the "latency" of UGT.

PMID- 22851617
TI  - Assessment of the drug interaction risk for remogliflozin etabonate, a sodium
      dependent glucose cotransporter-2 inhibitor: evidence from in vitro, human mass
      balance, and ketoconazole interaction studies.
AB  - Remogliflozin etabonate is the ester prodrug of remogliflozin, a selective sodium
      dependent glucose cotransporter-2 inhibitor. This work investigated the
      absorption, metabolism, and excretion of [(14)C]remogliflozin etabonate in
      humans, as well as the influence of P-glycoprotein (Pgp) and cytochrome P450
      (P450) enzymes on the disposition of remogliflozin etabonate and its metabolites
      to understand the risks for drug interactions. After a single oral 402 +/- 1.0 mg
      (106 +/- 0.3 MUCi) dose, [(14)C]remogliflozin etabonate is rapidly absorbed and
      extensively metabolized. The area under the concentration-time curve from 0 to
      infinity [AUC((0-infinity))] of plasma radioactivity was approximately 14-fold
      higher than the sum of the AUC((0-infinity)) of remogliflozin etabonate,
      remogliflozin, and 5-methyl-4-({4-[(1-methylethyl)oxy]phenyl}methyl)-1H-pyrazol-3
      yl-beta-d-glucopyranoside (GSK279782), a pharmacologically active N-dealkylated
      metabolite. Elimination half-lives of total radioactivity, remogliflozin
      etabonate, and remogliflozin were 6.57, 0.39, and 1.57 h, respectively. Products
      of remogliflozin etabonate metabolism are eliminated primarily via renal
      excretion, with 92.8% of the dose recovered in the urine. Three glucuronide
      metabolites made up the majority of the radioactivity in plasma and represent
      67.1% of the dose in urine, with 5-methyl-1-(1-methylethyl)-4-({4-[(1
      methylethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl-beta-d-glucopyranosiduronic acid
      (GSK1997711) representing 47.8% of the dose. In vitro studies demonstrated that
      remogliflozin etabonate and remogliflozin are Pgp substrates, and that CYP3A4 can
      form GSK279782 directly from remogliflozin. A ketoconazole clinical drug
      interaction study, along with the human mass balance findings, confirmed that
      CYP3A4 contributes less than 50% to remogliflozin metabolism, demonstrating that
      other enzyme pathways (e.g., P450s, UDP-glucuronosyltransferases, and
      glucosidases) make significant contributions to the drug's clearance. Overall,
      these studies support a low clinical drug interaction risk for remogliflozin
      etabonate due to the availability of multiple biotransformation pathways.

PMID- 22851618
TI  - Major incident experience and preparedness in a developing country.
AB  - BACKGROUND: Research shows that having previous experience of major incidents has
      a positive impact on awareness and preparedness of organizations. We investigated
      the effects of major incident experience on preparedness of health organizations
      on future disasters in Iran. METHODS: A qualitative study using a semistructured
      interview technique was conducted with 65 public health and therapeutic affairs
      managers. Analysis of the data was performed used the framework analysis
      technique, which was supported by qualitative research software. RESULTS: The
      study found that prior experience of major incidents results in better
      performance, coordination, and cooperation in response to future events. There
      was a positive effect on policy making and resource distribution and an increase
      in (1) preparedness activities, (2) raising population awareness, and (3)
      improving knowledge. However, the preparedness actions were predominantly
      individual-dependent. CONCLUSIONS: Our findings showed that to increase system
      efficiency and effectiveness within health organizations, an appropriate major
      incident management system is needed. The new system can use lessons learned from
      previous major incidents to better equip health organizations to cope with
      similar events in the future.

PMID- 22851619
TI  - Coronary CT angiography reduces unnecessary admissions and allows safe discharge
      of emergency department patients with low-to-intermediate risk chest pain.

PMID- 22851620
TI  - Aspirin prophylaxis in people without prior cardiovascular disease does not lead
      to reductions in cardiovascular death or cancer mortality.

PMID- 22851621
TI  - Why we need more breast cancer screening trials.

PMID- 22851622
TI  - Renal, cardiovascular and metabolic effects of fetal programming.

PMID- 22851623
TI  - Urinary angiotensinogen as a biomarker of chronic kidney disease: ready for prime
      time?

PMID- 22851624
TI  - Chronic kidney disease and life expectancy.

PMID- 22851625
TI  - The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary
      hyperoxaluria type III.

PMID- 22851626
TI  - The renal (myo-)fibroblast: a heterogeneous group of cells.
AB  - Several studies have demonstrated that mesenchymal stem cells have the capacity
      to reverse acute and chronic kidney injury in different experimental models by
      paracrine mechanisms. This paracrine action may be accounted for, at least in
      part, by microvesicles (MVs) released from mesenchymal stem cells, resulting in a
      horizontal transfer of mRNA, microRNA and proteins. MVs, released as exosomes
      from the endosomal compartment, or as shedding vesicles from the cell surface,
      are now recognized as being an integral component of the intercellular
      microenvironment. By acting as vehicles for information transfer, MVs play a
      pivotal role in cell-to-cell communication. This exchange of information between
      the injured cells and stem cells has the potential to be bi-directional. Thus,
      MVs may either transfer transcripts from injured cells to stem cells, resulting
      in reprogramming of their phenotype to acquire specific features of the tissue,
      or conversely, transcripts could be transferred from stem cells to injured cells,
      restraining tissue injury and inducing cell cycle re-entry of resident cells,
      leading to tissue self-repair. Upon administration with a therapeutic regimen,
      MVs mimic the effect of mesenchymal stem cells in various experimental models by
      inhibiting apoptosis and stimulating cell proliferation. In this review, we
      discuss whether MVs released from mesenchymal stem cells have the potential to be
      exploited in novel therapeutic approaches in regenerative medicine to repair
      damaged tissues, as an alternative to stem cell-based therapy.

PMID- 22851627
TI  - Therapeutic potential of mesenchymal stem cell-derived microvesicles.
AB  - Several studies have demonstrated that mesenchymal stem cells have the capacity
      to reverse acute and chronic kidney injury in different experimental models by
      paracrine mechanisms. This paracrine action may be accounted for, at least in
      part, by microvesicles (MVs) released from mesenchymal stem cells, resulting in a
      horizontal transfer of mRNA, microRNA and proteins. MVs, released as exosomes
      from the endosomal compartment, or as shedding vesicles from the cell surface,
      are now recognized as being an integral component of the intercellular
      microenvironment. By acting as vehicles for information transfer, MVs play a
      pivotal role in cell-to-cell communication. This exchange of information between
      the injured cells and stem cells has the potential to be bi-directional. Thus,
      MVs may either transfer transcripts from injured cells to stem cells, resulting
      in reprogramming of their phenotype to acquire specific features of the tissue,
      or conversely, transcripts could be transferred from stem cells to injured cells,
      restraining tissue injury and inducing cell cycle re-entry of resident cells,
      leading to tissue self-repair. Upon administration with a therapeutic regimen,
      MVs mimic the effect of mesenchymal stem cells in various experimental models by
      inhibiting apoptosis and stimulating cell proliferation. In this review, we
      discuss whether MVs released from mesenchymal stem cells have the potential to be
      exploited in novel therapeutic approaches in regenerative medicine to repair
      damaged tissues, as an alternative to stem cell-based therapy.

PMID- 22851628
TI  - Metabolic acidosis and kidney disease: does bicarbonate therapy slow the
      progression of CKD?
AB  - Metabolic acidosis is a common complication associated with progressive loss of
      kidney function. The diminishing ability of the kidneys to maintain acid-base
      homeostasis results in acid accumulation, leading to various complications such
      as impairment in nutritional status, worsened uremic bone disease and an
      association with increased mortality. In addition to these adverse effects which
      are related to acid retention, metabolic acidosis may also cause kidney damage,
      possibly through the stimulation of adaptive mechanisms aimed at maintaining acid
      base homeostasis in the face of decreasing kidney function. Recent clinical
      trials have suggested that correction or prevention of metabolic acidosis by
      alkali administration is able to attenuate kidney damage and to slow progression
      of chronic kidney disease (CKD), and may hence offer an effective, safe and
      affordable renoprotective strategy. We review the physiology and pathophysiology
      of acid-base homeostasis in CKD, the mechanisms whereby metabolic acidosis may be
      deleterious to kidney function, and the results of clinical trials suggesting a
      benefit of alkali therapy, with special attention to details related to the
      practical implementation of the results of these trials.

PMID- 22851630
TI  - FGF-23: the rise of a novel cardiovascular risk marker in CKD.
AB  - Elevated plasma levels of the phosphaturic hormone fibroblast growth factor 23
      (FGF-23) are a hallmark of chronic kidney disease (CKD)-mineral and bone
      disorder. FGF-23 allows serum phosphate levels within physiological limits to be
      maintained in progressive CKD until end-stage renal disease is reached. Despite
      its seemingly beneficial role in phosphate homeostasis, several prospective
      studies in dialysis patients and in patients with less advanced CKD associated
      elevated FGF-23 with poor cardiovascular and renal outcome. Moreover, very recent
      evidence suggests an adverse prognostic impact of elevated FGF-23 even in
      subjects without manifest CKD. These epidemiological data are supplemented by
      laboratory findings that reveal a pathophysiological role of FGF-23 in the
      pathogenesis of myocardial injury. In aggregate, these clinical and experimental
      data identify FGF-23 as a promising target of novel therapeutic interventions in
      CKD and beyond, which should be tested in future clinical trials.

PMID- 22851629
TI  - The consequences of chronic kidney disease on bone metabolism and growth in
      children.
AB  - Growth retardation, decreased final height and renal osteodystrophy (ROD) are
      common complications of childhood chronic kidney disease (CKD), resulting from a
      combination of abnormalities in the growth hormone (GH) axis, vitamin D
      deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and
      drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD-MBD)
      may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor
      growth, ROD, fractures, vascular calcifications, increased morbidity and
      mortality). In 2012, the clinical management of CKD-MBD in children needs to
      focus on three main objectives: (i) to provide an optimal growth in order to
      maximize the final height with an early management with recombinant GH therapy
      when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain
      acceptable bone quality and cardiovascular status and (iii) to correct all
      metabolic and clinical abnormalities that can worsen bone disease, growth and
      cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and
      25(OH)vitamin D deficiency. The aim of this review is to provide an overview of
      the mineral, bone and vascular abnormalities associated with CKD in children in
      terms of pathophysiology, diagnosis and clinical management.

PMID- 22851631
TI  - Fasting and postprandial activity of brown adipose tissue in healthy men.
AB  - The role of brown adipose tissue (BAT) in adult metabolism is poorly understood.
      This study aimed to examine the differential effects of an overnight fast and the
      postprandial state on BAT activity. METHODS: We included 10 healthy, lean male
      volunteers. BAT uptake of glucose was visualized using (18)F-FDG PET/CT during
      mild cold exposure. Each subject underwent PET/CT twice. The first scan was
      obtained after an overnight fast; the second after a standardized meal. RESULTS:
      (18)F-FDG uptake in BAT was observed in 6 of 10 volunteers. These subjects were
      found to have a higher maximal standardized uptake value when fasting (median,
      13.1 g/mL; range, 6.1-27.6 g/mL) than when in the postprandial state (median, 6.8
      g/mL; range, 2.1-13.4 g/mL) (P = 0.03). CONCLUSION: Cold-stimulated (18)F-FDG
      uptake by BAT in humans is more pronounced during fasting. The lower maximal
      standardized uptake value in the postprandial state may be explained by increased
      insulin-stimulated glucose uptake in muscle.

PMID- 22851633
TI  - PET imaging of alpha4beta2* nicotinic acetylcholine receptors: quantitative
      analysis of 18F-nifene kinetics in the nonhuman primate.
AB  - The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ((18)F
      nifene) is an alpha4beta2* nicotinic acetylcholine receptor (nAChR) agonist
      developed to provide accelerated in vivo equilibrium compared with existing
      alpha4beta2* radioligands. The goal of this work was to analyze the in vivo
      kinetic properties of (18)F-nifene with both kinetic modeling and graphical
      analysis techniques. METHODS: Dynamic PET experiments were performed on 4 rhesus
      monkeys (female; age range, 9-13 y) using a small-animal PET scanner. Studies
      began with a high-specific-activity (18)F-nifene injection, followed by a
      coinjection of (18)F-nifene and unlabeled nifene at 60 min. Sampling of arterial
      blood with metabolite analysis was performed throughout the experiment to provide
      a parent radioligand input function. In vivo kinetics were characterized with
      both a 1-tissue-compartment model (1TCM) and a 2-tissue-compartment model, Logan
      graphical methods (both with and without blood sampling), and the multilinear
      reference tissue model. Total distribution volumes and nondisplaceable binding
      potentials (BP(ND)) were used to compare regional binding of (18)F-nifene.
      Regions examined include the anteroventral thalamus, lateral geniculate body,
      frontal cortex, subiculum, and cerebellum. RESULTS: The rapid uptake and binding
      of (18)F-nifene in nAChR-rich regions of the brain was appropriately modeled
      using the 1TCM. No evidence for specific binding of (18)F-nifene in the
      cerebellum was detected on the basis of the coinjection studies, suggesting the
      suitability of the cerebellum as a reference region. Total distribution volumes
      in the cerebellum were 6.91 +/- 0.61 mL/cm(3). BP(ND) values calculated with the
      1TCM were 1.60 +/- 0.17, 1.35 +/- 0.16, 0.26 +/- 0.08, and 0.30 +/- 0.07 in the
      anteroventral thalamus, lateral geniculate body, frontal cortex, and subiculum,
      respectively. For all brain regions, there was a less than 0.04 absolute
      difference in the average BP(ND) values calculated with each of the 1TCM,
      multilinear reference tissue model, and Logan methods. CONCLUSION: The fast
      kinetic properties and specific regional binding of (18)F-nifene promote
      extension of the radioligand into preclinical animal models and human subjects.

PMID- 22851635
TI  - The synthesis and in vivo pharmacokinetics of fluorinated arachidonic acid:
      implications for imaging neuroinflammation.
AB  - Arachidonic acid (AA) is found in high concentrations in brain phospholipids and
      is released as a second messenger during neurotransmission and much more so
      during neuroinflammation and excitotoxicity. Upregulated brain AA metabolism
      associated with neuroinflammation has been imaged in rodents using [1-(14)C]AA
      and with PET in Alzheimer disease patients using [1-(11)C]AA. Radiotracer brain
      AA uptake is independent of cerebral blood flow, making it an ideal tracer
      despite altered brain functional activity. However, the 20.4-min radioactive half
      life of (11)C-AA and challenges of routinely synthesizing (11)C fatty acids limit
      their translational utility as PET biomarkers. METHODS: As a first step to
      develop a clinically useful (18)F-fluoroarachidonic acid ((18)F-FAA) with a long
      radioactive half-life of 109.8 min, we report here a high-yield stereoselective
      synthetic method of nonradioactive 20-(19)F-FAA. We tested its in vivo
      pharmacokinetics by infusing purified nonradioactive (19)F-FAA intravenously for
      5 min at 2 doses in unanesthetized mice and measured its plasma and brain
      distribution using gas chromatography-mass spectrometry. RESULTS: Incorporation
      coefficients of injected (19)F-FAA into brain phospholipids (ratio of brain (19)F
      FAA concentration to plasma input function) were 3- to 29-fold higher for choline
      glycerophospholipid and phosphatidylinositol than for ethanolamine
      glycerophospholipid and phosphatidylserine at each of the 2 tested doses. The
      selectivities and values of incorporation coefficients were comparable to those
      reported after [1-(14)C]AA (the natural arachidonate) infusion in mice.
      CONCLUSION: These results suggest that it would be worthwhile to translate our
      stereoselective synthetic method for (19)F-FAA to synthesize positron-emitting
      (18)F-FAA for human brain AA metabolism in neuroinflammatory disorders such as
      Alzheimer disease.

PMID- 22851636
TI  - Age effects on serotonin receptor 1B as assessed by PET.
AB  - Previous imaging studies have suggested that there is an age-related decline in
      brain serotonin (5-hydroxytryptamine) measures in healthy subjects. This paper
      addresses whether the availability of 5-hydroxytryptamine receptor 1B (5-HT(1B))
      is seen to decrease with aging via PET imaging. METHODS: Forty-eight healthy
      control subjects (mean age +/- SD, 30 +/- 10 y; age range, 18-61 y; 33 men, 15
      women) underwent (11)C-P943 scanning on a high-resolution PET tomograph. Regions
      were examined with and without gray matter masking, the latter in an attempt to
      control for age-related gray matter atrophy on nondisplaceable binding potential
      (BP(ND)) as determined by a validated multilinear reference tissue model.
      RESULTS: 5-HT(1B) BP(ND) decreased in the cortex at an average rate of 8% per
      decade without and 9% with gray matter masking. A negative association with age
      was also observed in all individual cortical regions. Differences in the putamen
      and pallidum (positive association) were significant after adjustment for
      multiple comparisons. No sex- or race-related effects on 5-HT(1B) BP(ND) were
      found in any regions. CONCLUSION: These findings indicate that age is a relevant
      factor for 5-HT(1B) in the cortex of healthy adults.

PMID- 22851637
TI  - Unexpected sensitivity of sst2 antagonists to N-terminal radiometal
      modifications.
AB  - Chelated somatostatin agonists have been shown to be sensitive to N-terminal
      radiometal modifications, with Ga-DOTA agonists having significantly higher
      binding affinity than their Lu-, In-, and Y-DOTA correlates. Recently,
      somatostatin antagonists have been successfully developed as alternative tracers
      to agonists. The aim of this study was to evaluate whether chelated somatostatin
      antagonists are also sensitive to radiometal modifications and how. We have
      synthesized 3 different somatostatin antagonists, DOTA-p-NO(2)-Phe-c[D-Cys-Tyr-D
      Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH(2), DOTA-Cpa-c[D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr
      Cys]-D-Tyr-NH(2) (DOTA-JR11), and DOTA-p-Cl-Phe-c[D-Cys-Tyr-D-Aph(Cbm)-Lys-Thr
      Cys]-D-Tyr-NH(2), and added various radiometals including In(III), Y(III),
      Lu(III), Cu(II), and Ga(III). We also replaced DOTA with 1,4,7
      triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) and added Ga(III). The
      binding affinity of somatostatin receptors 1 through 5 was evaluated in all
      cases. In all 3 resulting antagonists, the Ga-DOTA analogs were the lowest
      affinity radioligands, with a somatostatin receptor 2 binding affinity up to 60
      times lower than the respective Y-DOTA, Lu-DOTA, or In-DOTA compounds.
      Interestingly, however, substitution of DOTA by the NODAGA chelator was able to
      increase massively its binding affinity in contrast to the Ga-DOTA analog. The 3
      NODAGA analogs are antagonists in functional tests. In vivo biodistribution
      studies comparing (68)Ga-DOTATATE agonist with (68)Ga-DOTA-JR11 and (68)Ga-NODAGA
      JR11 showed not only that the JR11 antagonist radioligands were superior to the
      agonist ligands but also that (68)Ga-NODAGA-JR11 was the tracer of choice and
      preferable to (68)Ga-DOTA-JR11 in transplantable HEK293-hsst(2) tumors in mice.
      One may therefore generalize that somatostatin receptor 2 antagonists are
      sensitive to radiometal modifications and may preferably be coupled with a (68)Ga
      NODAGA chelator-radiometal complex.

PMID- 22851639
TI  - Among elderly residents of long term care facilities, a visit to the emergency
      department is associated with an increased risk of acquiring a new respiratory or
      gastrointestinal infection.

PMID- 22851640
TI  - Addition of certain herbal medicines to chemotherapy may increase survival and
      quality of life in patients with advanced colorectal cancer.

PMID- 22851641
TI  - Revealing the role of CD4(+) T cells in viral immunity.
AB  - Protective immunity to chronic and acute viral infection relies on both the
      innate and adaptive immune response. Although neutralizing antibody production by
      B cells and cytotoxic activity of CD8(+) T cells are well-accepted components of
      the adaptive immune response to viruses, identification of the specific role of
      CD4(+) T cells in protection has been more challenging to establish. Delineating
      the contribution of CD4(+) T cells has been complicated by their functional
      heterogeneity, breadth in antigen specificity, transient appearance in
      circulation, and sequestration in tissue sites of infection. In this minireview,
      we discuss recent progress in identifying the multiple roles of CD4(+) T cells in
      orchestrating and mediating the immune responses against viral pathogens. We
      highlight several recent reports, including one published in this issue, that
      have employed comprehensive and sophisticated approaches to provide new evidence
      for CD4(+) T cells as direct effectors in antiviral immunity.

PMID- 22851642
TI  - Self-renewal of thymocytes in the absence of competitive precursor replenishment.
AB  - Soon after transplantation of wild-type thymi into immunodeficient mice lacking
      functional T cell receptors, productive T cell development in the donor thymus
      ceases. This observation underlies one of the central dogmas of T cell biology:
      because thymocytes are seemingly short-lived, intrathymic T cell development
      depends on continuous import of lymphoid progenitors from the bone marrow. New
      work reinterprets the outcome of this classical experiment as being the result of
      competition for intrathymic niches specifically supporting the DN3 stage of early
      T cell development. Surprisingly, when this niche space is uncontested by
      immigrating host progenitors, development of T cells in the thymus grafts
      continues. These new findings suggest that early thymocytes do indeed have
      substantial self-renewing potential.

PMID- 22851643
TI  - Case study: ethical guidance for pediatric e-health research using examples from
      pain research with adolescents.
AB  - OBJECTIVE: The Internet is a frequently used platform for research in pediatric
      and health psychology. However, there is little pragmatic guidance as to ethical
      best practice of this research. The absence of guidance is particularly prominent
      for online research with children. Our objective is to outline ethical issues in
      e-health research with children and adolescents using two exemplar studies in
      pediatric pain research. METHODS: The first study is an asynchronous message
      board discussion amongst teenagers with pain who are frequent internet users.The
      second study is a web-based behavioral intervention for the management of
      adolescent pain. RESULTS: Each exemplar study is discussed in the context of
      specific ethical considerations related to recruitment, informed consent and
      debriefing, privacy and confidentiality, and participant safety. Ethical issues
      regarding the evaluation of online psychological interventions are also
      discussed. CONCLUSIONS: Guidance on optimal ethical practice in e-health research
      is summarized.

PMID- 22851645
TI  - A maximum-likelihood method to correct for allelic dropout in microsatellite data
      with no replicate genotypes.
AB  - Allelic dropout is a commonly observed source of missing data in microsatellite
      genotypes, in which one or both allelic copies at a locus fail to be amplified by
      the polymerase chain reaction. Especially for samples with poor DNA quality, this
      problem causes a downward bias in estimates of observed heterozygosity and an
      upward bias in estimates of inbreeding, owing to mistaken classifications of
      heterozygotes as homozygotes when one of the two copies drops out. One general
      approach for avoiding allelic dropout involves repeated genotyping of homozygous
      loci to minimize the effects of experimental error. Existing computational
      alternatives often require replicate genotyping as well. These approaches,
      however, are costly and are suitable only when enough DNA is available for
      repeated genotyping. In this study, we propose a maximum-likelihood approach
      together with an expectation-maximization algorithm to jointly estimate allelic
      dropout rates and allele frequencies when only one set of nonreplicated genotypes
      is available. Our method considers estimates of allelic dropout caused by both
      sample-specific factors and locus-specific factors, and it allows for deviation
      from Hardy-Weinberg equilibrium owing to inbreeding. Using the estimated
      parameters, we correct the bias in the estimation of observed heterozygosity
      through the use of multiple imputations of alleles in cases where dropout might
      have occurred. With simulated data, we show that our method can (1) effectively
      reproduce patterns of missing data and heterozygosity observed in real data; (2)
      correctly estimate model parameters, including sample-specific dropout rates,
      locus-specific dropout rates, and the inbreeding coefficient; and (3)
      successfully correct the downward bias in estimating the observed heterozygosity.
      We find that our method is fairly robust to violations of model assumptions
      caused by population structure and by genotyping errors from sources other than
      allelic dropout. Because the data sets imputed under our model can be
      investigated in additional subsequent analyses, our method will be useful for
      preparing data for applications in diverse contexts in population genetics and
      molecular ecology.

PMID- 22851644
TI  - DNA replication origin function is promoted by H3K4 di-methylation in
      Saccharomyces cerevisiae.
AB  - DNA replication is a highly regulated process that is initiated from replication
      origins, but the elements of chromatin structure that contribute to origin
      activity have not been fully elucidated. To identify histone post-translational
      modifications important for DNA replication, we initiated a genetic screen to
      identify interactions between genes encoding chromatin-modifying enzymes and
      those encoding proteins required for origin function in the budding yeast
      Saccharomyces cerevisiae. We found that enzymes required for histone H3K4
      methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase
      Bre1, are required for robust growth of several hypomorphic replication mutants,
      including cdc6-1. Consistent with a role for these enzymes in DNA replication, we
      found that both Set1 and Bre1 are required for efficient minichromosome
      maintenance. These phenotypes are recapitulated in yeast strains bearing
      mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of
      the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains
      lacking specific COMPASS complex members or containing H2B mutations that
      differentially affect H3K4 methylation states, we determined that these
      replication defects were due to loss of H3K4 di-methylation. Furthermore, histone
      H3K4 di-methylation is enriched at chromosomal origins. These data suggest that
      H3K4 di-methylation is necessary and sufficient for normal origin function. We
      propose that histone H3K4 di-methylation functions in concert with other histone
      post-translational modifications to support robust genome duplication.

PMID- 22851646
TI  - Comparative oncogenomics implicates the neurofibromin 1 gene (NF1) as a breast
      cancer driver.
AB  - Identifying genomic alterations driving breast cancer is complicated by tumor
      diversity and genetic heterogeneity. Relevant mouse models are powerful for
      untangling this problem because such heterogeneity can be controlled. Inbred
      Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors
      that have tumor gene expression profiles closely resembling mature human mammary
      luminal cell signatures. We genomically characterized mammary adenocarcinomas
      from these mice to identify cancer-causing genomic events that overlap common
      alterations in human breast cancer. Chaos3 tumors underwent recurrent copy number
      alterations (CNAs), particularly deletion of the RAS inhibitor Neurofibromin 1
      (Nf1) in nearly all cases. These overlap with human CNAs including NF1, which is
      deleted or mutated in 27.7% of all breast carcinomas. Chaos3 mammary tumor cells
      exhibit RAS hyperactivation and increased sensitivity to RAS pathway inhibitors.
      These results indicate that spontaneous NF1 loss can drive breast cancer. This
      should be informative for treatment of the significant fraction of patients whose
      tumors bear NF1 mutations.

PMID- 22851647
TI  - Estimating allele age and selection coefficient from time-serial data.
AB  - Recent advances in sequencing technologies have made available an ever-increasing
      amount of ancient genomic data. In particular, it is now possible to target
      specific single nucleotide polymorphisms in several samples at different time
      points. Such time-series data are also available in the context of experimental
      or viral evolution. Time-series data should allow for a more precise inference of
      population genetic parameters and to test hypotheses about the recent action of
      natural selection. In this manuscript, we develop a likelihood method to jointly
      estimate the selection coefficient and the age of an allele from time-serial
      data. Our method can be used for allele frequencies sampled from a single
      diallelic locus. The transition probabilities are calculated by approximating the
      standard diffusion equation of the Wright-Fisher model with a one-step process.
      We show that our method produces unbiased estimates. The accuracy of the method
      is tested via simulations. Finally, the utility of the method is illustrated with
      an application to several loci encoding coat color in horses, a pattern that has
      previously been linked with domestication. Importantly, given our ability to
      estimate the age of the allele, it is possible to gain traction on the important
      problem of distinguishing selection on new mutations from selection on standing
      variation. In this coat color example for instance, we estimate the age of this
      allele, which is found to predate domestication.

PMID- 22851648
TI  - Indirect genetic effects for survival in domestic chickens (Gallus gallus) are
      magnified in crossbred genotypes and show a parent-of-origin effect.
AB  - Through social interactions, individuals can affect one another's phenotype. The
      heritable effect of an individual on the phenotype of a conspecific is known as
      an indirect genetic effect (IGE). Although IGEs can have a substantial impact on
      heritable variation and response to selection, little is known about the genetic
      architecture of traits affected by IGEs. We studied IGEs for survival in domestic
      chickens (Gallus gallus), using data on two purebred lines and their reciprocal
      cross. Birds were kept in groups of four. Feather pecking and cannibalism caused
      mortality, as beaks were kept intact. Survival time was shorter in crossbreds
      than in purebreds, indicating outbreeding depression and the presence of
      nonadditive genetic effects. IGEs contributed the majority of heritable variation
      in crossbreds (87 and 72%) and around half of heritable variation in purebreds
      (65 and 44%). There was no evidence of dominance variance, neither direct nor
      indirect. Absence of dominance variance in combination with considerable
      outbreeding depression suggests that survival is affected by many loci. Direct
      indirect genetic correlations were moderately to highly negative in crossbreds (
      0.37 +/- 0.17 and -0.83 +/- 0.10), but low and not significantly different from
      zero in purebreds (0.20 +/- 0.21 and -0.28 +/- 0.18). Consequently, unlike
      purebreds, crossbreds would fail to respond positively to mass selection. The
      direct genetic correlation between both crosses was high (0.95 +/- 0.23), whereas
      the indirect genetic correlation was moderate (0.41 +/- 0.26). Thus, for IGEs, it
      mattered which parental line provided the sire and which provided the dam. This
      indirect parent-of-origin effect appeared to be paternally transmitted and is
      probably Z chromosome linked.

PMID- 22851649
TI  - Clonal interference in the evolution of influenza.
AB  - The seasonal influenza A virus undergoes rapid evolution to escape human immune
      response. Adaptive changes occur primarily in antigenic epitopes, the antibody
      binding domains of the viral hemagglutinin. This process involves recurrent
      selective sweeps, in which clusters of simultaneous nucleotide fixations in the
      hemagglutinin coding sequence are observed about every 4 years. Here, we show
      that influenza A (H3N2) evolves by strong clonal interference. This mode of
      evolution is a red queen race between viral strains with different beneficial
      mutations. Clonal interference explains and quantifies the observed sweep
      pattern: we find an average of at least one strongly beneficial amino acid
      substitution per year, and a given selective sweep has three to four driving
      mutations on average. The inference of selection and clonal interference is based
      on frequency time series of single-nucleotide polymorphisms, which are obtained
      from a sample of influenza genome sequences over 39 years. Our results imply that
      mode and speed of influenza evolution are governed not only by positive selection
      within, but also by background selection outside antigenic epitopes: immune
      adaptation and conservation of other viral functions interfere with each other.
      Hence, adapting viral proteins are predicted to be particularly brittle. We
      conclude that a quantitative understanding of influenza's evolutionary and
      epidemiological dynamics must be based on all genomic domains and functions
      coupled by clonal interference.

PMID- 22851650
TI  - A redundant function for the N-terminal tail of Ndc80 in kinetochore-microtubule
      interaction in Saccharomyces cerevisiae.
AB  - The N-terminal tail of Ndc80 is essential for kinetochore-microtubule binding in
      human cells but is not required for viability in yeast. We show that the yeast
      Ndc80 tail is required for timely mitotic progression and accurate chromosome
      segregation. The tail is essential when cells are limited for Dam1, demonstrating
      a redundant function for the Ndc80 and Dam1 complexes in vivo.

PMID- 22851651
TI  - Cellular memory of acquired stress resistance in Saccharomyces cerevisiae.
AB  - Cellular memory of past experiences has been observed in several organisms and
      across a variety of experiences, including bacteria "remembering" prior
      nutritional status and amoeba "learning" to anticipate future environmental
      conditions. Here, we show that Saccharomyces cerevisiae maintains a multifaceted
      memory of prior stress exposure. We previously demonstrated that yeast cells
      exposed to a mild dose of salt acquire subsequent tolerance to severe doses of
      H(2)O(2). We set out to characterize the retention of acquired tolerance and in
      the process uncovered two distinct aspects of cellular memory. First, we found
      that H(2)O(2) resistance persisted for four to five generations after cells were
      removed from the prior salt treatment and was transmitted to daughter cells that
      never directly experienced the pretreatment. Maintenance of this memory did not
      require nascent protein synthesis after the initial salt pretreatment, but rather
      required long-lived cytosolic catalase Ctt1p that was synthesized during salt
      exposure and then distributed to daughter cells during subsequent cell divisions.
      In addition to and separable from the memory of H(2)O(2) resistance, these cells
      also displayed a faster gene-expression response to subsequent stress at >1000
      genes, representing transcriptional memory. The faster gene-expression response
      requires the nuclear pore component Nup42p and serves an important function by
      facilitating faster reacquisition of H(2)O(2) tolerance after a second cycle of
      salt exposure. Memory of prior stress exposure likely provides a significant
      advantage to microbial populations living in ever-changing environments.

PMID- 22851653
TI  - Reperfusion-triggered stress protein response in the myocardium is blocked by
      post-conditioning. Systems biology pathway analysis highlights the key role of
      the canonical aryl-hydrocarbon receptor pathway.
AB  - AIMS: Ischaemic post-conditioning (IPost-Co) exerts cardioprotection by
      diminishing ischaemia/reperfusion injury. Yet, the mechanisms involved in such
      protection remain largely unknown. We have investigated the effects of IPost-Co
      in cardiac cells and in heart performance using molecular, proteomic and
      functional approaches. METHODS AND RESULTS: Pigs underwent 1.5 h mid-left
      anterior descending balloon occlusion and then were sacrificed without
      reperfusion (ischaemia; n= 7), subjected to 2.5 h of cardiac reperfusion and
      sacrificed (n= 5); or subjected to IPost-Co before reperfusion and sacrificed 0.5
      h (n= 4) and 2.5 h (n= 5) afterwards. A sham-operated group was included (n= 4).
      Ischaemic and non-ischaemic myocardium was obtained for molecular/histological
      analysis. Proteomic analysis was performed by two-dimensional electrophoresis
      followed by matrix-assisted laser desorption/ionization-time-of-flight
      identification. Potential protein networks involved were identified by
      bioinformatics and Ingenuity Pathway Analysis (IPA). Cardiac function was
      assessed by echocardiography. IPost-Co diminished (up to 2.5 h) reperfusion
      induced apoptosis of both the intrinsic and extrinsic pathways whereas it did not
      affect reperfusion-induced Akt/mammalian target of rapamycin (mTOR)/P70S6K
      activation. Proteomic studies showed that IPost-Co reverted 43% of cardiac
      cytoplasmic protein changes observed during ischaemia and ischaemia +
      reperfusion. Systems biology assessment revealed significant changes in the aryl
      hydrocarbon receptor (AhR) pathway (cell damage related). Bioinformatic data were
      confirmed since the expression of HSP90, AhR, ANRT, and beta-tubulin (involved in
      AhR-signalling transduction) were accordingly modified after IPost-Co. IPost-Co
      rescued 52% of the left ventricle-at-risk compared with reperfusion alone and
      resulted in a ~30% relative improvement in left ventricular ejection fraction (P
      <0.05). CONCLUSION: IPost-Co improves cardiac function post-myocardial infarction
      and reduces reperfusion-induced cell damage by down-regulation of the AhR
      signalling transduction pathway ultimately leading to infarct size reduction.

PMID- 22851654
TI  - Transcatheter aortic valve implantation 10-year anniversary: review of current
      evidence and clinical implications.
AB  - Surgical aortic valve replacement (SAVR) is currently the standard of care to
      treat patients with severe symptomatic aortic stenosis (AS) and is generally
      accepted to alleviate symptoms and prolong survival. Based on the results of
      randomized trials, transcatheter aortic valve implantation (TAVI) is the new
      standard of care for patients with symptomatic AS who are deemed 'inoperable'.
      Debatably, TAVI is also an alternative to SAVR in selected patients who are at
      high risk but operable. As we approach 10 years of clinical experience with TAVI,
      with over 50 000 implantations in 40 countries, a review of the current
      literature and clinical outcomes with this rapidly evolving technology is
      appropriate.

PMID- 22851652
TI  - A cytoplasmic suppressor of a nuclear mutation affecting mitochondrial functions
      in Drosophila.
AB  - Phenotypes relevant to oxidative phosphorylation (OXPHOS) in eukaryotes are
      jointly determined by nuclear and mitochondrial DNA (mtDNA). Thus, in humans, the
      variable clinical presentations of mitochondrial disease patients bearing the
      same primary mutation, whether in nuclear or mitochondrial DNA, have been
      attributed to putative genetic determinants carried in the "other" genome, though
      their identity and the molecular mechanism(s) by which they might act remain
      elusive. Here we demonstrate cytoplasmic suppression of the mitochondrial disease
      like phenotype of the Drosophila melanogaster nuclear mutant tko(25t), which
      includes developmental delay, seizure sensitivity, and defective male courtship.
      The tko(25t) strain carries a mutation in a mitoribosomal protein gene, causing
      OXPHOS deficiency due to defective intramitochondrial protein synthesis.
      Phenotypic suppression was associated with increased mtDNA copy number and
      increased mitochondrial biogenesis, as measured by the expression levels of porin
      voltage dependent anion channel and Spargel (PGC1alpha). Ubiquitous
      overexpression of Spargel in tko(25t) flies phenocopied the suppressor,
      identifying it as a key mechanistic target thereof. Suppressor-strain mtDNAs
      differed from related nonsuppressor strain mtDNAs by several coding-region
      polymorphisms and by length and sequence variation in the noncoding region (NCR),
      in which the origin of mtDNA replication is located. Cytoplasm from four of five
      originally Wolbachia-infected strains showed the same suppressor effect, whereas
      that from neither of two uninfected strains did so, suggesting that the stress of
      chronic Wolbachia infection may provide evolutionary selection for improved
      mitochondrial fitness under metabolic stress. Our findings provide a paradigm for
      understanding the role of mtDNA genotype in human disease.

PMID- 22851655
TI  - Transcatheter aortic valve implantation: 10-year anniversary part II: clinical
      implications.
AB  - Transcatheter aortic valve implantation (TAVI) has been increasingly recognized
      as a curative treatment for severe aortic stenosis (AS). Despite important
      improvements in current device technology and implantation techniques, specific
      complications still remain and warrant consideration. Vascular complications and
      peri-procedural neurological events were the first concerns to emerge with this
      new technology. Recently, significant post procedural para-valvular leak has been
      shown to be more frequent after TAVI than after surgical aortic valve replacement
      (SAVR), and its potential association with worse long-term prognostic has raised
      concerns. In moving toward treatment of lower risk populations, structural
      integrity and long-term durability of heat valve prosthesis are becoming of
      central importance. Emerging technologies and newer generations of devices seem
      promising in dealing with these matters.

PMID- 22851656
TI  - Emergence of fatal avian influenza in New England harbor seals.
AB  - From September to December 2011, 162 New England harbor seals died in an outbreak
      of pneumonia. Sequence analysis of postmortem samples revealed the presence of an
      avian H3N8 influenza A virus, similar to a virus circulating in North American
      waterfowl since at least 2002 but with mutations that indicate recent adaption to
      mammalian hosts. These include a D701N mutation in the viral PB2 protein,
      previously reported in highly pathogenic H5N1 avian influenza viruses infecting
      people. Lectin staining and agglutination assays indicated the presence of the
      avian-preferred SAalpha-2,3 and mammalian SAalpha-2,6 receptors in seal
      respiratory tract, and the ability of the virus to agglutinate erythrocytes
      bearing either the SAalpha-2,3 or the SAalpha-2,6 receptor. The emergence of this
      A/harbor seal/Massachusetts/1/2011 virus may herald the appearance of an H3N8
      influenza clade with potential for persistence and cross-species transmission.
      IMPORTANCE: The emergence of new strains of influenza virus is always of great
      public concern, especially when the infection of a new mammalian host has the
      potential to result in a widespread outbreak of disease. Here we report the
      emergence of an avian influenza virus (H3N8) in New England harbor seals which
      caused an outbreak of pneumonia and contributed to a U.S. federally recognized
      unusual mortality event (UME). This outbreak is particularly significant, not
      only because of the disease it caused in seals but also because the virus has
      naturally acquired mutations that are known to increase transmissibility and
      virulence in mammals. Monitoring the spillover and adaptation of avian viruses in
      mammalian species is critically important if we are to understand the factors
      that lead to both epizootic and zoonotic emergence.

PMID- 22851657
TI  - Zinc competition among the intestinal microbiota.
AB  - Bioavailable levels of trace metals, such as iron and zinc, for bacterial growth
      in nature are sufficiently low that most microbes have evolved high-affinity
      binding and transport systems. The microbe Campylobacter jejuni lives in the
      gastrointestinal tract of chickens, the principal source of human infection. A
      high-affinity ABC transporter for zinc uptake is required for Campylobacter
      survival in chicken intestines in the presence of a normal microbiota but not
      when chickens are raised with a limited microbiota. Mass spectrometric analysis
      of cecal contents revealed the presence of numerous zinc-binding proteins in
      conventional chicks compared to the number in limited-microbiota chicks. The
      presence of a microbiota results in the production of host zinc-binding enzymes,
      causing a growth restriction for bacteria that lack the high-affinity zinc
      transporter. Such transporters in a wide range of pathogenic bacteria make them
      good targets for the development of broad-spectrum antimicrobials. IMPORTANCE:
      Zinc is an essential trace element for the growth of most organisms. Quantities
      of zinc inside cells are highly regulated, as too little zinc does not support
      growth, while too much zinc is toxic. Numerous bacterial cells require zinc
      uptake systems for growth and virulence. The work presented here demonstrates
      that the microbiota in the gastrointestinal tract reduces the quantity of zinc.
      Without a high-affinity zinc transporter, Campylobacter jejuni, a commensal
      organism of chickens, is unable to replicate or colonize the gastrointestinal
      tract. This is the first demonstration of zinc competition between microbiota in
      the gastrointestinal tract of a host. These results could have profound
      implications in the field of microbial pathogenesis and in our understanding of
      host metabolism and the microbiota.

PMID- 22851658
TI  - MreA functions in the global regulation of methanogenic pathways in
      Methanosarcina acetivorans.
AB  - Results are presented supporting a regulatory role for the product of the MA3302
      gene locus (designated MreA) previously annotated as a hypothetical protein in
      the methanogenic species Methanosarcina acetivorans of the domain Archaea.
      Sequence analysis of MreA revealed identity to the TrmB family of transcription
      factors, albeit the sequence is lacking the sensor domain analogous to TrmBL2,
      abundant in nonmethanogenic species of the domain Archaea. Transcription of mreA
      was highly upregulated during growth on acetate versus methylotrophic substrates,
      and an mreA deletion (DeltamreA) strain was impaired for growth with acetate in
      contrast to normal growth with methylotrophic substrates. Transcriptional
      profiling of acetate-grown cells identified 280 genes with altered expression in
      the DeltamreA strain versus the wild-type strain. Expression of genes unique to
      the acetate pathway decreased whereas expression of genes unique to
      methylotrophic metabolism increased in the DeltamreA strain relative to the wild
      type, results indicative of a dual role for MreA in either the direct or indirect
      activation of acetate-specific genes and repression of methylotrophic-specific
      genes. Gel shift experiments revealed specific binding of MreA to promoter
      regions of regulated genes. Homologs of MreA were identified in M. acetivorans
      and other Methanosarcina species for which expression patterns indicate roles in
      regulating methylotrophic pathways. IMPORTANCE: Species in the domain Archaea
      utilize basal transcription machinery resembling that of the domain Eukarya,
      raising questions addressing the role of numerous putative transcription factors
      identified in sequenced archaeal genomes. Species in the genus Methanosarcina are
      ideally suited for investigating principles of archaeal transcription through
      analysis of the capacity to utilize a diversity of substrates for growth and
      methanogenesis. Methanosarcina species switch pathways in response to the most
      energetically favorable substrate, metabolizing methylotrophic substrates in
      preference to acetate marked by substantial regulation of gene expression.
      Although conversion of the methyl group of acetate accounts for most of the
      methane produced in Earth's biosphere, no proteins involved in the regulation of
      genes in the acetate pathway have been reported. The results presented here
      establish that MreA participates in the global regulation of diverse methanogenic
      pathways in the genus Methanosarcina. Finally, the results contribute to a
      broader understanding of transcriptional regulation in the domain Archaea.

PMID- 22851660
TI  - Influenza virus resistance to human neutralizing antibodies.
AB  - The human antibody repertoire has an exceptionally large capacity to recognize
      new or changing antigens through combinatorial and junctional diversity
      established at the time of V(D)J recombination and through somatic hypermutation.
      Influenza viruses exhibit a relentless capacity to escape the human antibody
      response by altering the amino acids of their surface proteins in hypervariable
      domains that exhibit a high level of structural plasticity. Both parties in this
      high-stakes game of shape shifting drive structural evolution of their functional
      proteins (the B cell receptor/antibody on one side and the viral hemagglutinin
      and neuraminidase proteins on the other) using error-prone polymerase systems. It
      is likely that most of the genetic mutations that occur in these systems are
      deleterious, resulting in the failure of the B cell or virus with mutations to
      propagate in the immune repertoire or viral quasispecies. A subset of mutations
      is tolerated in functional surface proteins that enter the B cell or virus
      progeny pool. In both cases, selection occurs in the population of mutated and
      unmutated species. In cases where the functional avidity of the B cell receptor
      is increased significantly, that clone may be selected for preferential
      expansion. In contrast, an influenza virus that "escapes" the inhibitory effect
      of secreted antibodies may represent a high proportion of the progeny virus in
      that host. The recent paper by O'Donnell et al. [C. D. O'Donnell et al., mBio
      3(3):e00120-12, 2012] identifies a mechanism for antibody resistance that does
      not require escape from binding but rather achieves a greater efficiency in
      replication.

PMID- 22851659
TI  - Low levels of beta-lactam antibiotics induce extracellular DNA release and
      biofilm formation in Staphylococcus aureus.
AB  - Subminimal inhibitory concentrations of antibiotics have been shown to induce
      bacterial biofilm formation. Few studies have investigated antibiotic-induced
      biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal
      was to measure S. aureus biofilm formation in the presence of low levels of beta
      lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant
      Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains
      were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added
      to cultures at concentrations ranging from 0* to 1* MIC. Biofilm formation was
      measured in 96-well microtiter plates using a crystal violet binding assay.
      Autoaggregation was measured using a visual test tube settling assay.
      Extracellular DNA was quantitated using agarose gel electrophoresis. All four
      antibiotics induced biofilm formation in some strains. The amount of biofilm
      induction was as high as 10-fold and was inversely proportional to the amount of
      biofilm produced by the strain in the absence of antibiotics. MRSA strains of
      lineages USA300, USA400, and USA500 exhibited the highest levels of methicillin
      induced biofilm induction. Biofilm formation induced by low-level methicillin was
      inhibited by DNase. Low-level methicillin also induced DNase-sensitive
      autoaggregation and extracellular DNA release. The biofilm induction phenotype
      was absent in a strain deficient in autolysin (atl). Our findings demonstrate
      that subminimal inhibitory concentrations of beta-lactam antibiotics
      significantly induce autolysin-dependent extracellular DNA release and biofilm
      formation in some strains of S. aureus. IMPORTANCE: The widespread use of
      antibiotics as growth promoters in agriculture may expose bacteria to low levels
      of the drugs. The aim of this study was to investigate the effects of low levels
      of antibiotics on bacterial autoaggregation and biofilm formation, two processes
      that have been shown to foster genetic exchange and antibiotic resistance. We
      found that low levels of beta-lactam antibiotics, a class commonly used in both
      clinical and agricultural settings, caused significant autoaggregation and
      biofilm formation by the important human pathogen Staphylococcus aureus. Both
      processes were dependent on cell lysis and release of DNA into the environment.
      The effect was most pronounced among multidrug-resistant strains known as
      methicillin-resistant S. aureus (MRSA). These results may shed light on the
      recalcitrance of some bacterial infections to antibiotic treatment in clinical
      settings and the evolution of antibiotic-resistant bacteria in agricultural
      settings.

PMID- 22851661
TI  - Cysteinyl leukotriene receptor antagonist montelukast ameliorates acute lung
      injury following haemorrhagic shock in rats.
AB  - OBJECTIVES: The aim of this study was to assess the possible protective effect of
      montelukast against haemorrhagic shock-induced acute lung injury by interfering
      with inflammatory and oxidative pathways. Acute lung injury following
      haemorrhagic shock/resuscitation is an important contributor to late morbidity
      and mortality in trauma patients. Haemorrhagic shock (HS), followed by
      resuscitation, is considered to be an insult that frequently induces systemic
      inflammatory response syndrome and oxidative stress, resulting in multiple-organ
      dysfunction syndrome, including microvascular changes and microscopic damage
      termed acute lung paraynchymal injury. Montelukast is a cysteinyl leukotriene
      receptor antagonist that exerts an anti-inflammatory and antioxidant influence.
      METHODS: Eighteen adult albino rats were assigned to three groups of six. In
      Group I, the 'sham' group, rats underwent all the surgical procedures but neither
      haemorrhagic shock nor resuscitation was carried out. Group II--the 'HS' induced,
      untreated group--was the control and underwent HS for one hour before being
      resuscitated with Ringer's lactate for one hour. Group III--the 'montelukast'
      group--underwent HS and treatment with montelukast (7 mg/kg i.p. injection) 30
      min before the induction of HS, with the same dose repeated just before the
      reperfusion period. At the end of the experiment, two hours after completion of
      resuscitation, blood samples were collected for measurement of serum tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The trachea was then
      isolated and bronchoalveolar lavage was carried out for measurement of
      leukotriene B(4) (LTB(4)), leukotriene C(4) (LTC(4)) and total protein. The lungs
      were harvested and the left lung was homogenized for measurement of
      malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed
      in 10% formalin for histological examination. RESULTS: Montelukast treatment
      (Group III) significantly reduced the total lung injury score, compared with the
      HS group (Group II) (P < 0.05). Montelukast also significantly decreased serum
      TNF-alpha and IL-6; lung MDA; bronchoalveolar lavage fluid (BALF) LTB(4), LTC(4)
      & total protein compared with the HS group (P < 0.05). Montelukast treatment
      significantly inhibited decrease in the lung GSH levels, compared with the HS
      group (P < 0.05). CONCLUSIONS: The results of the present study reveal that
      montelukast may ameliorate lung injury in shocked rats by interfering with
      inflammatory and oxidative pathways, implicating the role of leukotrienes in the
      pathogenesis of haemorrhagic shock-induced lung inflammation.

PMID- 22851662
TI  - Minimally invasive resection of thymomas with the da Vinci(r) Surgical System.
AB  - OBJECTIVES: The resection of thymic tumours requires completeness and may be
      technically challenging due to the anatomical proximity of the delicate
      mediastinal structures. An open approach by sternotomy is still recommended in
      all cases with locally extended disease. Video-assisted thoracoscopic surgery is
      feasible, but limited by the two-dimensional vision and the impaired mobility of
      the instruments. We evaluated the da Vinci(r) Surgical System for the resection
      of various mediastinal pathologies, particularly thymomas. METHODS: Among 105
      patients operated on by robotic assisted thoracoscopic surgery (RATS) for
      mediastinal tumours between 27 August 2004 and 12 July 2011, 20 patients with
      thymomas were studied prospectively. Of these, 10 males with a median age of 53
      years, with a well-circumscribed thymic lesion on computed tomography (CT) and a
      diameter of <6 cm were resected by RATS alone, and selected ones (n = 3), with a
      diameter of >6 cm, underwent a hybrid procedure with a contralateral thoracotomy
      on the side of the main tumour extension. A regular follow-up with chest CT scans
      was performed every 6 months. RESULTS: Thymoma resection was complete in all
      patients. Partial pericardial resection was needed in five and pulmonary
      resection in two patients. Eighty-five percent of patients had an R0 resection.
      Histological classifications included thymoma WHO type A (n = 3), AB (n = 8), B1
      2 (n = 5) and B3 (n = 4). All B3 thymomas received adjuvant radiotherapy. No
      intraoperative complications occurred. The median hospitalization time was 5 days
      (range 2-14 days). There were no local, but two pleural, recurrences. After a
      median observation time of 26 months, 19 patients (95%) are alive. CONCLUSIONS:
      Well-circumscribed thymomas can be safely and completely resected with the da
      Vinci(r) Surgical System with excellent short- and mid-term outcomes. Selected
      tumours with large diameters may be resectable using a hybrid procedure combining
      RATS with a thoracotomy.

PMID- 22851663
TI  - In vivo diagnosis of lymphocytic colitis by confocal laser endomicroscopy.

PMID- 22851664
TI  - High prevalence of hyperplastic polyposis syndrome (serrated polyposis) in the
      NHS bowel cancer screening programme.

PMID- 22851665
TI  - Adiponectin: a relevant player in obesity-related colorectal cancer?

PMID- 22851666
TI  - A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses
      colon tumorigenesis via regular exercise.
AB  - OBJECTIVE: Several epidemiological studies have shown that regular exercise can
      prevent the onset of colon cancer, although the underlying mechanism is unclear.
      Myokines are secreted skeletal muscle proteins responsible for some exercise
      induced health benefits including metabolic improvement and anti-inflammatory
      effects in organs. The purpose of this study was to identify new myokines that
      contribute to the prevention of colon tumorigenesis. METHODS: To identify novel
      secreted muscle-derived proteins, DNA microarrays were used to compare the
      transcriptome of muscle tissue in sedentary and exercised young and old mice. The
      level of circulating secreted protein acidic and rich in cysteine (SPARC) was
      measured in mice and humans that performed a single bout of exercise. The effect
      of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion
      and function of SPARC was examined in culture experiments. RESULTS: A single bout
      of exercise increased the expression and secretion of SPARC in skeletal muscle in
      both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse
      model, regular low-intensity exercise significantly reduced the formation of
      aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore,
      regular exercise enhanced apoptosis in colon mucosal cells and increased the
      cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null
      mice. Culture experiments showed that SPARC secretion from myocytes was induced
      by cyclic stretch and inhibited proliferation with apoptotic effect of colon
      cancer cells. CONCLUSIONS: These findings suggest that exercise stimulates SPARC
      secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by
      increasing apoptosis.

PMID- 22851667
TI  - When dermatology meets gastroenterology: a case of odynophagia.

PMID- 22851669
TI  - Doctor's perspective: the 'new' UK 4-h target.

PMID- 22851668
TI  - HCCR-1 for detecting small hepatocellular carcinoma latent in a cirrhotic liver:
      a prospective cohort study.

PMID- 22851670
TI  - Rescuer fatigue under the 2010 ERC guidelines, and its effect on cardiopulmonary
      resuscitation (CPR) performance.
AB  - BACKGROUND: Updated life-support guidelines were published by the European
      Resuscitation Council (ERC) in 2010, increasing the required depth and rate of
      chest compression delivery. This study sought to determine the impact of these
      guidelines on rescuer fatigue and cardiopulmonary resuscitation (CPR)
      performance. METHODS: 62 Health science students performed 5 min of conventional
      CPR in accordance with the 2010 ERC guidelines. A SkillReporter manikin was used
      to objectively assess temporal change in determinants of CPR quality.
      Participants subjectively reported their end-fatigue levels, using a visual
      analogue scale, and the point at which they believed fatigue was affecting CPR
      delivery. RESULTS: 49 (79%) participants reported that fatigue affected their CPR
      performance, at an average of 167 s. End fatigue averaged 49.5/100 (range 0-95).
      The proportion of chest compressions delivered correctly decreased from 52% in
      min 1 to 39% in min 5, approaching significance (p=0.071). A significant decline
      in chest compressions reaching the recommended depth occurred between the first
      (53%) and fifth (38%) min (p=0.012). Almost half this decline (6%) was between
      the first and second minutes of CPR. Neither chest compression rate, nor rescue
      breath volume, were affected by rescuer fatigue. CONCLUSION: Fatigue affects
      chest compression delivery within the second minute of CPR under the 2010 ERC
      guidelines, and is poorly judged by rescuers. Rescuers should, therefore, be
      encouraged to interchange after 2 min of CPR delivery. Team leaders should be
      advised to not rely on rescuers to self-report fatigue, and should, instead,
      monitor for its effects.

PMID- 22851671
TI  - Serial high-sensitivity troponin measurements for the rapid exclusion of acute
      myocardial infarction in low-risk patients.
AB  - High-sensitivity troponin assays facilitate the rapid exclusion of acute
      myocardial infarction (AMI). However, elevated results are also seen in other
      conditions causing myocardial injury. Serial measurements increase the
      specificity for AMI, helping to rapidly identify patients for whom
      revascularisation may be appropriate. In this study, we explore a strategy for
      rapidly excluding AMI in symptomatic patients using serial high-sensitivity
      troponin measurements. MAIN FINDINGS: (1) all patients presenting more than 3 h
      after symptom onset with a negative result had a second negative result; (2) AMI
      was excluded in all patients with two results falling below the lower limit of
      detection of a standard troponin assay by 8 h post-symptom onset.

PMID- 22851672
TI  - The role of synthetic colloids for the volume resuscitation of critically ill
      adults.

PMID- 22851673
TI  - Regulation and dysregulation of cardiac ryanodine receptor (RyR2) open
      probability during diastole in health and disease.

PMID- 22851674
TI  - Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP.
AB  - The synergic effect of luminal Ca(2+), cytosolic Ca(2+), and cytosolic adenosine
      triphosphate (ATP) on activation of cardiac ryanodine receptor (RYR2) channels
      was examined in planar lipid bilayers. The dose-response of RYR2 gating activity
      to ATP was characterized at a diastolic cytosolic Ca(2+) concentration of 100 nM
      over a range of luminal Ca(2+) concentrations and, vice versa, at a diastolic
      luminal Ca(2+) concentration of 1 mM over a range of cytosolic Ca(2+)
      concentrations. Low level of luminal Ca(2+) (1 mM) significantly increased the
      affinity of the RYR2 channel for ATP but without substantial activation of the
      channel. Higher levels of luminal Ca(2+) (8-53 mM) markedly amplified the effects
      of ATP on the RYR2 activity by selectively increasing the maximal RYR2 activation
      by ATP, without affecting the affinity of the channel to ATP. Near-diastolic
      cytosolic Ca(2+) levels (<500 nM) greatly amplified the effects of luminal
      Ca(2+). Fractional inhibition by cytosolic Mg(2+) was not affected by luminal
      Ca(2+). In models, the effects of luminal and cytosolic Ca(2+) could be explained
      by modulation of the allosteric effect of ATP on the RYR2 channel. Our results
      suggest that luminal Ca(2+) ions potentiate the RYR2 gating activity in the
      presence of ATP predominantly by binding to a luminal site with an apparent
      affinity in the millimolar range, over which local luminal Ca(2+) likely varies
      in cardiac myocytes.

PMID- 22851675
TI  - The delayed rectifier potassium conductance in the sarcolemma and the transverse
      tubular system membranes of mammalian skeletal muscle fibers.
AB  - A two-microelectrode voltage clamp and optical measurements of membrane potential
      changes at the transverse tubular system (TTS) were used to characterize delayed
      rectifier K currents (IK(V)) in murine muscle fibers stained with the
      potentiometric dye di-8-ANEPPS. In intact fibers, IK(V) displays the canonical
      hallmarks of K(V) channels: voltage-dependent delayed activation and decay in
      time. The voltage dependence of the peak conductance (gK(V)) was only accounted
      for by double Boltzmann fits, suggesting at least two channel contributions to
      IK(V). Osmotically treated fibers showed significant disconnection of the TTS and
      displayed smaller IK(V), but with similar voltage dependence and time decays to
      intact fibers. This suggests that inactivation may be responsible for most of the
      decay in IK(V) records. A two-channel model that faithfully simulates IK(V)
      records in osmotically treated fibers comprises a low threshold and steeply
      voltage-dependent channel (channel A), which contributes ~31% of gK(V), and a
      more abundant high threshold channel (channel B), with shallower voltage
      dependence. Significant expression of the IK(V)1.4 and IK(V)3.4 channels was
      demonstrated by immunoblotting. Rectangular depolarizing pulses elicited step
      like di-8-ANEPPS transients in intact fibers rendered electrically passive. In
      contrast, activation of IK(V) resulted in time- and voltage-dependent
      attenuations in optical transients that coincided in time with the peaks of IK(V)
      records. Normalized peak attenuations showed the same voltage dependence as peak
      IK(V) plots. A radial cable model including channels A and B and K diffusion in
      the TTS was used to simulate IK(V) and average TTS voltage changes. Model
      predictions and experimental data were compared to determine what fraction of
      gK(V) in the TTS accounted simultaneously for the electrical and optical data.
      Best predictions suggest that K(V) channels are approximately equally distributed
      in the sarcolemma and TTS membranes; under these conditions, >70% of IK(V) arises
      from the TTS.

PMID- 22851676
TI  - A data-driven model of a modal gated ion channel: the inositol 1,4,5
      trisphosphate receptor in insect Sf9 cells.
AB  - The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) channel is crucial for
      the generation and modulation of intracellular Ca(2+) signals in animal cells. To
      gain insight into the complicated ligand regulation of this ubiquitous channel,
      we constructed a simple quantitative continuous-time Markov-chain model from the
      data. Our model accounts for most experimentally observed gating behaviors of
      single native IP(3)R channels from insect Sf9 cells. Ligand (Ca(2+) and IP(3))
      dependencies of channel activity established six main ligand-bound channel
      complexes, where a complex consists of one or more states with the same ligand
      stoichiometry and open or closed conformation. Channel gating in three distinct
      modes added one complex and indicated that three complexes gate in multiple
      modes. This also restricted the connectivity between channel complexes. Finally,
      latencies of channel responses to abrupt ligand concentration changes defined a
      model with specific network topology between 9 closed and 3 open states. The
      model with 28 parameters can closely reproduce the equilibrium gating statistics
      for all three gating modes over a broad range of ligand concentrations. It also
      captures the major features of channel response latency distributions. The model
      can generate falsifiable predictions of IP(3)R channel gating behaviors and
      provide insights to both guide future experiment development and improve IP(3)R
      channel gating analysis. Maximum likelihood estimates of the model parameters and
      of the parameters in the De Young-Keizer model yield strong statistical evidence
      in favor of our model. Our method is simple and easily applicable to the dynamics
      of other ion channels and molecules.

PMID- 22851677
TI  - Regulation of voltage-gated potassium channels by PI(4,5)P2.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) regulates activities of
      numerous ion channels including inwardly rectifying potassium (K(ir)) channels,
      KCNQ, TRP, and voltage-gated calcium channels. Several studies suggest that
      voltage-gated potassium (K(V)) channels might be regulated by PI(4,5)P(2). Wide
      expression of K(V) channels in different cells suggests that such regulation
      could have broad physiological consequences. To study regulation of K(V) channels
      by PI(4,5)P(2), we have coexpressed several of them in tsA-201 cells with a G
      protein-coupled receptor (M(1)R), a voltage-sensitive lipid 5-phosphatase (Dr
      VSP), or an engineered fusion protein carrying both lipid 4-phosphatase and 5
      phosphatase activity (pseudojanin). These tools deplete PI(4,5)P(2) with
      application of muscarinic agonists, depolarization, or rapamycin, respectively.
      PI(4,5)P(2) at the plasma membrane was monitored by Forster resonance energy
      transfer (FRET) from PH probes of PLCdelta1 simultaneously with whole-cell
      recordings. Activation of Dr-VSP or recruitment of pseudojanin inhibited K(V)7.1,
      K(V)7.2/7.3, and K(ir)2.1 channel current by 90-95%. Activation of M(1)R
      inhibited K(V)7.2/7.3 current similarly. With these tools, we tested for
      potential PI(4,5)P(2) regulation of activity of K(V)1.1/K(V)beta1.1, K(V)1.3,
      K(V)1.4, and K(V)1.5/K(V)beta1.3, K(V)2.1, K(V)3.4, K(V)4.2, K(V)4.3 (with
      different KChIPs and DPP6-s), and hERG/KCNE2. Interestingly, we found a
      substantial removal of inactivation for K(V)1.1/K(V)beta1.1 and K(V)3.4,
      resulting in up-regulation of current density upon activation of M(1)R but no
      changes in activity upon activating only VSP or pseudojanin. The other channels
      tested except possibly hERG showed no alteration in activity in any of the assays
      we used. In conclusion, a depletion of PI(4,5)P(2) at the plasma membrane by
      enzymes does not seem to influence activity of most tested K(V) channels, whereas
      it does strongly inhibit members of the K(V)7 and K(ir) families.

PMID- 22851678
TI  - Estradiol partially recapitulates murine pituitary cell cycle response to
      pregnancy.
AB  - Because pregnancy and estrogens both induce pituitary lactotroph hyperplasia, we
      assessed the expression of pituitary cell cycle regulators in two models of
      murine pituitary hyperplasia. Female mice were assessed during nonpregnancy,
      pregnancy, day of delivery, and postpartum. We also implanted estradiol (E(2))
      pellets in female mice and studied them for 2.5 months. Pituitary weight in
      female mice increased 2-fold after E(2) administration and 1.4-fold at day of
      delivery, compared with placebo-treated or nonpregnant females. Pituitary
      proliferation, as assessed by proliferating cell nuclear antigen and/or Ki-67
      staining, increased dramatically during both mid-late pregnancy and E(2)
      administration, and lactotroph hyperplasia was also observed. Pregnancy induced
      pituitary cell cycle proliferative and inhibitory responses at the G(1)/S
      checkpoint. Differential cell cycle regulator expression included cyclin
      dependent kinase inhibitors, p21(Cip1), p27(Kip1), and cyclin D1. Pituitary cell
      cycle responses to E(2) administration partially recapitulated those effects
      observed at mid-late pregnancy, coincident with elevated circulating mouse E(2),
      including increased expression of proliferating cell nuclear antigen, Ki-67,
      p15(INK4b), and p21(Cip1). Nuclear localization of pituitary p21(Cip1) was
      demonstrated at mid-late pregnancy but not during E(2) administration, suggesting
      a cell cycle inhibitory role for p21(Cip1) in pregnancy, yet a possible
      proproliferative role during E(2) administration. Most observed cell cycle
      protein alterations were reversed postpartum. Murine pituitary meets the demand
      for prolactin during lactation associated with induction of both cell
      proliferative and inhibitory pathways, mediated, at least partially, by
      estradiol.

PMID- 22851679
TI  - Chromogranin A induces the biogenesis of granules with calcium- and actin
      dependent dynamics and exocytosis in constitutively secreting cells.
AB  - Chromogranins are a family of acidic glycoproteins that play an active role in
      hormone and neuropeptide secretion through their crucial role in secretory
      granule biogenesis in neuroendocrine cells. However, the molecular mechanisms
      underlying their granulogenic activity are still not fully understood. Because we
      previously demonstrated that the expression of the major component of secretory
      granules, chromogranin A (CgA), is able to induce the formation of secretory
      granules in nonendocrine COS-7 cells, we decided to use this model to dissect the
      mechanisms triggered by CgA leading to the biogenesis and trafficking of such
      granules. Using quantitative live cell imaging, we first show that CgA-induced
      organelles exhibit a Ca(2+)-dependent trafficking, in contrast to native vesicle
      stomatitis virus G protein-containing constitutive vesicles. To identify the
      proteins that confer such properties to the newly formed granules, we developed
      CgA-stably-expressing COS-7 cells, purified their CgA-containing granules by
      subcellular fractionation, and analyzed the granule proteome by liquid
      chromatography-tandem mass spectrometry. This analysis revealed the association
      of several cytosolic proteins to the granule membrane, including GTPases,
      cytoskeleton-based molecular motors, and other proteins with actin- and/or Ca(2+)
      binding properties. Furthermore, disruption of cytoskeleton affects not only the
      distribution and the transport but also the Ca(2+)-evoked exocytosis of the CgA
      containing granules, indicating that these granules interact with microtubules
      and cortical actin for the regulated release of their content. These data
      demonstrate for the first time that the neuroendocrine factor CgA induces the
      recruitment of cytoskeleton-, GTP-, and Ca(2+)-binding proteins in constitutively
      secreting COS-7 cells to generate vesicles endowed with typical dynamics and
      exocytotic properties of neuroendocrine secretory granules.

PMID- 22851680
TI  - Caffeine inhibits EGF-stimulated trophoblast cell motility through the inhibition
      of mTORC2 and Akt.
AB  - Impaired trophoblast invasion is associated with pregnancy disorders such as
      early pregnancy loss and preeclampsia. There is evidence to suggest that the
      consumption of caffeine during pregnancy may increase the risk of pregnancy loss;
      however, little is known about the direct effect of caffeine on normal
      trophoblast biology. Our objectives were to examine the effect of caffeine on
      trophoblast migration and motility after stimulation with epidermal growth factor
      (EGF) and to investigate the intracellular signaling pathways involved in this
      process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT
      derived cell line SGHPL-4 were used to study the effect of caffeine on EGF
      stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were
      further used to study the effect of caffeine and cAMP on EGF-stimulated invasion
      of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated
      intracellular signaling pathways leading to the activation of Akt were
      investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated
      primary EVT and SGHPL-4 cell motility. EGF stimulation activates
      phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation.
      Although cAMP inhibits both motility and invasion, it does not inhibit the
      activation of Akt, indicating that the effects of caffeine seen in this study are
      independent of cAMP. Further investigation indicated a role for mammalian target
      of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of
      caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated
      trophoblast invasion and motility in vitro and so could adversely influence
      trophoblast biology in vivo.

PMID- 22851681
TI  - Identification and fine mapping of qCTH4, a quantitative trait loci controlling
      the chlorophyll content from tillering to heading in rice (Oryza sativa L.).
AB  - The chlorophyll content is one of the most important traits selected by breeders,
      and it is controlled by quantitative trait loci (QTLs) derived from natural
      variations in rice. We analyzed the QTL controlling chlorophyll content by using
      94 RILs derived from a cross between 2 japonica rice cultivars,
      Lijiangxintuanheigu (LTH) and Shennong265 (SN265). Twenty-two QTLs controlling
      chlorophyll content at tillering stage, heading stage, and maturity stage were
      detected, respectively. Among them, Rice cv. LTH had a positive allele only at 1
      locus (qCTH4) on chromosome 4. Further analysis indicated that the genetic effect
      of qCTH4 was the net effects within the period from tillering to heading. The QTL
      qCTH4 controlling chlorophyll content from tillering to heading locates between
      RM255 and RM349 on chromosome 4 with a LOD score 19.41, and the QTL qCTH4
      explains 61.42% of phenotypic variation. In order to eliminate the influence of
      other QTLs, 1 single residual heterozygous plant, RH-qCTH4, was selected based on
      the genotypes of 114 Simple Sequence Repeat (SSR) markers. Using the segregating
      population derived from RH-qCTH4 by self-crossing, this region was narrowed down
      to an interval between RM3276 and RM17494 in an approximately 771kb target
      region. These results are useful for map-based cloning of qCTH4 and for marker
      assisted selection of high photosynthetic efficiency variety.

PMID- 22851682
TI  - Microglia: a novel treatment target in gliomas.

PMID- 22851683
TI  - Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet
      function and clinical outcome- a systematic review.
AB  - BACKGROUND: Clopidogrel as an adjunct to aspirin has improved outcomes after
      acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet
      effect when proton pump inhibitors (PPIs) are co-administered. Despite
      corroborating data from retrospective studies, new clinical data fuel the
      controversy on this issue. PURPOSE: Systematic review of the impact of the
      addition of PPIs to clopidogrel on platelet function and cardiovascular outcome.
      DATA SOURCES: PubMed, Web-of-Science, Cochrane Database and reference lists of
      related articles. STUDY SELECTION: Published articles on controlled studies
      addressing the addition of PPIs to clopidogrel. Platelet function studies
      describe patients as well as healthy volunteers. Clinical studies concern
      patients using clopidogrel for acute coronary syndromes or because of stent
      implantation for stable coronary disease. DATA EXTRACTION: Two investigators
      independently reviewed the identified articles for eligibility, and one author
      extracted the data. DATA SYNTHESIS: In 70% (7/10) of the laboratory studies
      examining healthy volunteers on clopidogrel, addition of PPIs resulted in a
      significant reduction in platelet inhibition. For patients, this was observed in
      11/18 (61%) studies. The 33 clinical studies showed significant heterogeneity in
      observed outcomes, with risk ratios for major adverse cardiovascular events
      varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in
      only two studies. Consequently, imbalances between prognosticators at baseline
      and PPI prescription bias markedly contributed to the variability in results.
      CONCLUSIONS: Despite indications of reduced antiplatelet activity ex vivo in the
      case of PPI administration in clopidogrel users, data on the clinical
      consequences are controversial. With the accumulating evidence from better
      designed, prospective clinical studies, an adverse effect of PPI use on clinical
      outcome in patients on clopidogrel cannot be substantiated. This review
      challenges the validity of conclusions based on quantitative analyses of
      predominantly non-randomised data.

PMID- 22851684
TI  - Use of troponin to diagnose periprocedural myocardial infarction: effect on
      composite endpoints in the British Bifurcation Coronary Study (BBC ONE).
AB  - BACKGROUND: Periprocedural myocardial infarction (PMI; ESC/ACC type 4a) is
      diagnosed on the basis of elevation of cardiac enzymes more than three times the
      99th centile upper reference limit. Recent guidelines recommend the use of
      troponin instead of creatine kinase (CK) to diagnose PMI, but this assay
      increases diagnostic sensitivity, while the clinical significance of small
      increases in troponin remains undetermined. We examined the effects of using the
      new definition on the incidence of a composite endpoint (previously defined by
      CK) in a contemporary clinical randomised trial-the British Bifurcation Coronary
      Study (BBC ONE). METHODS: The BBC ONE trial randomly allocated 500 patients with
      coronary bifurcation lesions to either a simple or complex stenting strategy. The
      composite primary endpoint (CPEP) included death, myocardial infarction (MI) (PMI
      plus subsequent MI) and target vessel failure, at 9 months. RESULTS: In BBC ONE
      the CPEP occurred in 8% versus 15.2% in the simple and complex groups,
      respectively (HR 2.02, 95% CI 1.17 to 3.47, p=0.009). This difference was largely
      driven by PMI, which occurred in nine (3.6%) versus 28 (11.2%) patients (HR 3.24,
      95% CI 1.53 to 6.86, p=0.001). Using troponin, PMI would have occurred in 71
      (28.4%) versus 114 (45.6%) patients, respectively (HR 1.61, 95% CI 1.27 to 2.05,
      p=0.001), and the CPEP in 32% versus 48% of patients (HR 1.50, 95% CI 1.2 to
      1.87, p=0.001). Use of troponin increased MI detection fivefold, from 7.4% to
      37.0% overall. CONCLUSIONS: Use of troponin would have led to a fivefold increase
      in diagnosis of PMI in the BBC ONE trial. Incorporation of PMI into a composite
      endpoint may no longer be justified in many interventional trials.

PMID- 22851685
TI  - Elastic properties of the ascending aorta in patients with alpha1-antitrypsin
      deficiency (Z homozygotes).
AB  - OBJECTIVE AND DESIGN: alpha1-Antitrypsin deficiency (AATD) is a genetic disorder
      that may be a pathogenic factor in vascular aneurysms and dissection. The aim of
      this study was to measure the diameters of the Valsalva sinuses (VS), sinotubular
      junction (STJ), ascending aorta (AA) and aortic arch (AAr) and elastic properties
      of the AA (distensibility, stiffness and tissue Doppler imaging (TDI strain)) in
      AATD subjects. PATIENTS: 33 AATD subjects (all Z-homozygous, 17 male, 16 female)
      were examined. Aortic elastic properties, namely, distensibility and stiffness
      index, were calculated from the echocardiographically-derived thoracic aortic
      diameters and TDI strain was measured on the wall of the AA 3 cm above the aortic
      valve. The results were compared with those obtained in healthy controls matched
      for age, sex and body mass index. RESULTS: AATD subjects had larger aortic
      diameters (VS: 3.5 +/- 0.5 vs 3.2 +/- 0.5 cm, p<0.05; STJ 2.7 +/- 0.4 vs 2.4 +/-
      0.4 cm, p<0.01; AA 3.3 +/- 0.5 vs 2.9 +/- 0.4 cm, p<0.01; AAr 2.3 +/- 0.3 vs 2.1
      +/- 0.3 cm, p=0.05); greater aortic stiffness 14.9 +/- 11.9 versus 7.4 +/- 4.4
      (pure numbers, p<0.005); and less aortic distensibility 2.4 +/- 1.8 versus 4.0 +/
      2.6 10(-6)*cm(2)*dyne(-1), p<0.005. Peak systolic (S) and diastolic (E and A)
      waves of the aortic wall TDI were similar in patients and controls (S wave: 5.4
      +/- 1.6 vs 5.9 +/- 2.3 cm/s; E wave: -4.8 +/- 2.2 vs -4.5 +/- 2.2 cm/s; A wave: 
      6.1 +/- 2.2 vs -6.2 +/- 2.4 cm/s) while TDI strain of the aortic wall was lesser
      in patients than controls (-14.7 +/- 8.0% vs -28.3 +/- 7.1%, p<0.001).
      CONCLUSIONS: AATD subjects have a larger AA with abnormal elastic properties as
      compared to controls. The increase in stiffness, decrease in distensibility and
      abnormal strain of the aortic wall may all reflect pathological changes in its
      elastic tissue.

PMID- 22851686
TI  - Insulin resistance and cancer: epidemiological evidence.
AB  - Epidemiological research into insulin resistance has focused on excess body
      weight, type 2 diabetes mellitus (DM), physical activity, and coffee consumption.
      These common modifiable factors have also been suggested to play a role in the
      process of carcinogenesis via associations with insulin resistance. Findings of
      systematic literature reviews and meta-analyses have generally supported an
      association between excess body weight and DM with an increased risk of colon
      cancer in males, and of liver, pancreatic, and endometrial cancers. Inverse
      relationships between these cancers and physical activity and coffee consumption
      have been shown, both of which are known to reduce the risk of DM. Interventions
      directed at or involving these variables should contribute to decreasing the risk
      of insulin resistance-associated cancer.

PMID- 22851687
TI  - Cancer risk after medical exposure to radioactive iodine in benign thyroid
      diseases: a meta-analysis.
AB  - Radioiodine-131 ((131)I) is widely used for diagnosis and treatment of benign
      thyroid diseases. Observational studies have not been conclusive about the
      carcinogenic potential of (131)I and we therefore conducted a meta-analysis. We
      performed a literature search till September 2011 which included (131)I as a
      diagnostic or treatment modality ((131)I for treatment of thyroid cancer was
      excluded). Data on 64 different organ or organ group subsets comprising 22 029
      exposed subjects in the therapeutic cohorts and 24 799 in the diagnostic cohorts
      in seven studies were included. Outcome was pooled as the relative risk (RR)
      using both standard and bias adjusted methods. Quality assessment was performed
      using a study-specific instrument. No increase in overall (RR 1.06, 95% CI: 0.94
      1.19), main organ group or combined organ group (four groups known to concentrate
      (131)I; RR 1.11, 95% CI: 0.94-1.31) risks was demonstrable. Individual organs
      demonstrated a higher risk for kidney (RR 1.70, 95% CI: 1.15-2.51) and thyroid
      (RR 1.99, 95% CI: 1.22-3.26) cancers with a strong trend for stomach cancer (RR
      1.11, 95% CI: 0.92-1.33). A thyroid dose effect was seen for diagnostic doses.
      While there is no increase in the overall burden of cancer, an increase in risk
      to a few organs is seen which requires substantiation. The possible increase in
      thyroid cancer risk following diagnostic (131)I use should no longer be of
      concern given that it has effectively been replaced by the use of 99mTc
      pertechnetate.

PMID- 22851688
TI  - Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the
      charged disordered segments of eIF4G and eIF2beta stabilizes the 48S
      preinitiation complex and promotes its shift to the initiation mode.
AB  - During translation initiation in Saccharomyces cerevisiae, an Arg- and Ser-rich
      segment (RS1 domain) of eukaryotic translation initiation factor 4G (eIF4G) and
      the Lys-rich segment (K-boxes) of eIF2beta bind three common partners, eIF5,
      eIF1, and mRNA. Here, we report that both of these segments are involved in mRNA
      recruitment and AUG recognition by distinct mechanisms. First, the eIF4G-RS1
      interaction with the eIF5 C-terminal domain (eIF5-CTD) directly links eIF4G to
      the preinitiation complex (PIC) and enhances mRNA binding. Second, eIF2beta-K
      boxes increase mRNA binding to the 40S subunit in vitro in a manner reversed by
      the eIF5-CTD. Third, mutations altering eIF4G-RS1, eIF2beta-K-boxes, and eIF5-CTD
      restore the accuracy of start codon selection impaired by an eIF2beta mutation in
      vivo, suggesting that the mutual interactions of the eIF segments within the PIC
      prime the ribosome for initiation in response to start codon selection. We
      propose that the rearrangement of interactions involving the eIF5-CTD promotes
      mRNA recruitment through mRNA binding by eIF4G and eIF2beta and assists the start
      codon-induced release of eIF1, the major antagonist of establishing
      tRNA(i)(Met):mRNA binding to the P site.

PMID- 22851689
TI  - Activating transcription factor 3 regulates immune and metabolic homeostasis.
AB  - Integration of metabolic and immune responses during animal development ensures
      energy balance, permitting both growth and defense. Disturbed homeostasis causes
      organ failure, growth retardation, and metabolic disorders. Here, we show that
      the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards
      metabolic and immune system homeostasis. Loss of Atf3 results in chronic
      inflammation and starvation responses mounted primarily by the larval gut
      epithelium, while the fat body suffers lipid overload, causing energy imbalance
      and death. Hyperactive proinflammatory and stress signaling through NF
      kappaB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes
      important for immune defense, digestion, and lipid metabolism. Reducing the dose
      of either FOXO or Relish normalizes both lipid metabolism and gene expression in
      atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the
      Drosophila mutant phenotypes, improving their survival. The single Drosophila
      Atf3 may incorporate the diversified roles of two related mammalian proteins.

PMID- 22851690
TI  - The combined deletion of S6K1 and Akt2 deteriorates glycemic control in a high
      fat diet.
AB  - Signaling downstream of mechanistic target of rapamycin complexes 1 and 2 (mTORC1
      and mTORC2) controls specific and distinct aspects of insulin action and nutrient
      homeostasis in an interconnected and as yet unclear way. Mice lacking the mTORC1
      substrate S6 kinase 1 (S6K1) maintain proper glycemic control with a high-fat
      diet. This phenotype is accompanied by insulin hypersensitivity, Akt- and AMP
      activated kinase upregulation, and increased lipolysis in adipose tissue and
      skeletal muscle. Here, we show that, when S6K1 inactivation is combined with the
      deletion of the mTORC2 substrate Akt2, glucose homeostasis is compromised due to
      defects in both insulin action and beta-cell function. After a high-fat diet, the
      S6K1(-/-) Akt2(-/-) double-mutant mice do not become obese, though they are
      severely hyperglycemic. Our data demonstrate that S6K1 is required for pancreatic
      beta-cell growth and function during adaptation to insulin resistance states.
      Strikingly, the inactivation of two targets of mTOR and phosphatidylinositol 3
      kinase signaling is sufficient to reproduce major hallmarks of type 2 diabetes.

PMID- 22851691
TI  - Interleukin-10-induced neutrophil gelatinase-associated lipocalin production in
      macrophages with consequences for tumor growth.
AB  - Tumor cell-derived factors, such as interleukin 10 (IL-10), polarize macrophages
      toward a regulatory M2 phenotype, characterized by the expression of anti
      inflammatory cytokines and protumorigenic mediators. Here we explored molecular
      mechanisms allowing IL-10 to upregulate the protumorigenic protein NGAL in
      primary human macrophages. Reporter assays of full-length or deletion constructs
      of the NGAL promoter provided evidence that NGAL production is STAT3 dependent,
      activated downstream of the IL-10-Janus kinase (Jak) axis, as well as being
      C/EBPbeta dependent. The involvement of STAT3 and C/EBPbeta was shown by
      chromatin immunoprecipitation (ChIP) and ChIP-Western analysis, as well as decoy
      oligonucleotides scavenging both STAT3 and C/EBPbeta in human macrophages.
      Furthermore, the production of NGAL in macrophages in response to IL-10 induces
      cellular growth and proliferation of MCF-7 breast cancer cells. We conclude that
      both STAT3 and C/EBPbeta are needed to elicit IL-10-mediated NGAL expression in
      primary human macrophages. Macrophage-secreted NGAL shapes the protumorigenic
      macrophage phenotype to promote growth of MCF-7 breast cancer cells. Our data
      point to a macrophage-dependent IL-10-STAT3-NGAL axis that might contribute to
      tumor progression.

PMID- 22851692
TI  - The DPY-30 domain and its flanking sequence mediate the assembly and modulation
      of flagellar radial spoke complexes.
AB  - RIIa is known as the dimerization and docking (D/D) domain of the cyclic AMP
      (cAMP)-dependent protein kinase. However, numerous molecules, including radial
      spoke protein 2 (RSP2) in Chlamydomonas flagella, also contain an RIIa or a
      similar DPY-30 domain. To elucidate new roles of D/D domain-containing proteins,
      we investigated a panel of RSP2 mutants. An RSP2 mutant had paralyzed flagella
      defective in RSP2 and multiple subunits near the spokehead. New transgenic
      strains lacking only the DPY-30 domain in RSP2 were also paralyzed. In contrast,
      motility was restored in strains that lacked only RSP2's calmodulin-binding C
      terminal region. These cells swam normally in dim light but could not maintain
      typical swimming trajectories under bright illumination. In both deletion
      transgenic strains, the subunits near the spokehead were restored, but their firm
      attachment to the spokestalk required the DPY-30 domain. We postulate that the
      DPY-30-helix dimer is a conserved two-prong linker, required for normal motility,
      organizing duplicated subunits in the radial spoke stalk and formation of a
      symmetrical spokehead. Further, the dispensable calmodulin-binding region appears
      to fine-tune the spokehead for regulation of "steering" motility in the green
      algae. Thus, in general, D/D domains may function to localize molecular modules
      for both the assembly and modulation of macromolecular complexes.

PMID- 22851693
TI  - beta-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the
      cytosol for TAK1-dependent NF-kappaB activation.
AB  - Interleukin-1 (IL-1) receptor-associated kinase (IRAK1) is phosphorylated,
      ubiquitinated, and degraded upon IL-1 stimulation. IRAK1 can be ubiquitinated
      through both K48- and K63-linked polyubiquitin chains upon IL-1 stimulation.
      While the Pellino proteins have been shown to meditate K63-linked
      polyubiquitination on IRAK1, the E3 ligase for K48-linked ubiquitination of IRAK1
      has not been identified. In this study, we report that the SCF (Skp1-Cullin1-F
      box)-beta-TrCP complex functions as the K48-linked ubiquitination E3 ligase for
      IRAK1. IL-1 stimulation induced the interaction of IRAK1 with Cullin1 and beta
      TrCP. Knockdown of beta-TrCP1 and beta-TrCP2 attenuated the K48-linked
      ubiquitination and degradation of IRAK1. Importantly, beta-TrCP deficiency
      abolished the translocation TAK1-TRAF6 complex from the membrane to the cytosol,
      resulting in a diminishment of the IL-1-induced TAK1-dependent pathway. Taken
      together, these results implicate a positive role of beta-TrCP-mediated IRAK1
      degradation in IL-1-induced TAK1 activation.

PMID- 22851694
TI  - Nek4 regulates entry into replicative senescence and the response to DNA damage
      in human fibroblasts.
AB  - When explanted into culture, normal human cells exhibit a finite number of cell
      divisions before entering a proliferative arrest termed replicative senescence.
      To identify genes essential for entry into replicative senescence, we performed
      an RNA interference (RNAi)-based loss-of-function screen and found that
      suppression of the Never in Mitosis Gene A (NIMA)-related protein kinase gene
      NEK4 disrupted timely entry into senescence. NEK4 suppression extended the number
      of population doublings required to reach replicative senescence in several human
      fibroblast strains and resulted in decreased transcription of the cyclin
      dependent kinase inhibitor p21. NEK4-suppressed cells displayed impaired cell
      cycle arrest in response to double-stranded DNA damage, and mass spectrometric
      analysis of Nek4 immune complexes identified a complex containing DNA-dependent
      protein kinase catalytic subunit [DNA-PK(cs)], Ku70, and Ku80. NEK4 suppression
      causes defects in the recruitment of DNA-PK(cs) to DNA upon induction of double
      stranded DNA damage, resulting in reduced p53 activation and H2AX
      phosphorylation. Together, these observations implicate Nek4 as a novel regulator
      of replicative senescence and the response to double-stranded DNA damage.

PMID- 22851695
TI  - Mediator promotes CENP-a incorporation at fission yeast centromeres.
AB  - At Schizosaccharomyces pombe centromeres, heterochromatin formation is required
      for de novo incorporation of the histone H3 variant CENP-A(Cnp1), which in turn
      directs kinetochore assembly and ultimately chromosome segregation during
      mitosis. Noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (Pol II)
      directs heterochromatin formation through not only the RNA interference (RNAi)
      machinery but also RNAi-independent RNA processing factors. Control of
      centromeric ncRNA transcription is therefore a key factor for proper centromere
      function. We here demonstrate that Mediator directs ncRNA transcription and
      regulates centromeric heterochromatin formation in fission yeast. Mediator
      colocalizes with Pol II at centromeres, and loss of the Mediator subunit Med20
      causes a dramatic increase in pericentromeric transcription and desilencing of
      the core centromere. As a consequence, heterochromatin formation is impaired via
      both the RNAi-dependent and -independent pathways, resulting in loss of CENP
      A(Cnp1) from the core centromere, a defect in kinetochore function, and a severe
      chromosome segregation defect. Interestingly, the increased centromeric
      transcription observed in med20Delta cells appears to directly block CENP-A(Cnp1)
      incorporation since inhibition of Pol II transcription can suppress the observed
      phenotypes. Our data thus identify Mediator as a crucial regulator of ncRNA
      transcription at fission yeast centromeres and add another crucial layer of
      regulation to centromere function.

PMID- 22851696
TI  - TRAF6-dependent Act1 phosphorylation by the IkappaB kinase-related kinases
      suppresses interleukin-17-induced NF-kappaB activation.
AB  - Interleukin-17 (IL-17) is critically involved in the pathogenesis of various
      inflammatory disorders. IL-17 receptor (IL-17R)-proximal signaling complex (IL
      17R-Act1-TRAF6) is essential for IL-17-mediated NF-kappaB activation, while IL-17
      mediated mRNA stability is TRAF6 independent. Recently, inducible IkappaB kinase
      (IKKi) has been shown to phosphorylate Act1 on Ser 311 to mediate IL-17-induced
      mRNA stability. Here we show that TANK binding kinase 1 (TBK1), the other IKK
      related kinase, directly phosphorylated Act1 on three other Ser sites to suppress
      IL-17R-mediated NF-kappaB activation. IL-17 stimulation activated TBK1 and
      induced its association with Act1. IKKi also phosphorylated Act1 on the three
      serine sites and played a redundant role with TBK1 in suppressing IL-17-induced
      NF-kappaB activation. Act1 phosphorylation on the three sites inhibited its
      association with TRAF6 and consequently NF-kappaB activation in IL-17R signaling.
      Interestingly, TRAF6, but not TRAF3, which is the upstream adaptor of the IKK
      related kinases in antiviral signaling, was critical for IL-17-induced Act1
      phosphorylation. TRAF6 was essential for IL-17-induced TBK1 activation, its
      association with Act1, and consequent Act1 phosphorylation. Our findings define a
      new role for the IKK-related kinases in suppressing IL-17-mediated NF-kappaB
      activation through TRAF6-dependent Act1 phosphorylation.

PMID- 22851697
TI  - Crystal structure and functional analysis of JMJD5 indicate an alternate
      specificity and function.
AB  - JMJD5 is a Jumonji C (JmjC) protein that has been implicated in breast cancer
      tumorigenesis, circadian rhythm regulation, embryological development, and
      osteoclastogenesis. Recently, JMJD5 (also called KDM8) has been reported to
      demethylate dimethylated Lys-36 in histone H3 (H3K36me2), regulating genes that
      control cell cycle progression. Here, we report high-resolution crystal
      structures of the human JMJD5 catalytic domain in complex with the substrate 2
      oxoglutarate (2-OG) and the inhibitor N-oxalylglycine (NOG). The structures
      reveal a beta-barrel fold that is conserved in the JmjC family and a long shallow
      cleft that opens into the enzyme's active site. A comparison with other JmjC
      enzymes illustrates that JMJD5 shares sequence and structural homology with the
      asparaginyl and histidinyl hydroxylase FIH-1 (factor inhibiting hypoxia-inducible
      factor 1 [HIF-1]), the lysyl hydroxylase JMJD6, and the RNA hydroxylase TYW5 but
      displays limited homology to JmjC lysine demethylases (KDMs). Contrary to
      previous findings, biochemical assays indicate that JMJD5 does not display
      demethylase activity toward methylated H3K36 nor toward the other methyllysines
      in the N-terminal tails of histones H3 and H4. Together, these results imply that
      JMJD5 participates in roles independent of histone demethylation and may function
      as a protein hydroxylase given its structural homology with FIH-1 and JMJD6.

PMID- 22851698
TI  - Expression profiling during mammary epithelial cell three-dimensional
      morphogenesis identifies PTPRO as a novel regulator of morphogenesis and ErbB2
      mediated transformation.
AB  - Identification of genes that are upregulated during mammary epithelial cell
      morphogenesis may reveal novel regulators of tumorigenesis. We have demonstrated
      that gene expression programs in mammary epithelial cells grown in monolayer
      cultures differ significantly from those in three-dimensional (3D) cultures. We
      identify a protein tyrosine phosphate, PTPRO, that was upregulated in mature MCF
      10A mammary epithelial 3D structures but had low to undetectable levels in
      monolayer cultures. Downregulation of PTPRO by RNA interference inhibited
      proliferation arrest during morphogenesis. Low levels of PTPRO expression
      correlated with reduced survival for breast cancer patients, suggesting a tumor
      suppressor function. Furthermore, we showed that the receptor tyrosine kinase
      ErbB2/HER2 is a direct substrate of PTPRO and that loss of PTPRO increased ErbB2
      induced cell proliferation and transformation, together with tyrosine
      phosphorylation of ErbB2. Moreover, in patients with ErbB2-positive breast
      tumors, low PTPRO expression correlated with poor clinical prognosis compared to
      ErbB2-positive patients with high levels of PTPRO. Thus, PTPRO is a novel
      regulator of ErbB2 signaling, a potential tumor suppressor, and a novel
      prognostic marker for patients with ErbB2-positive breast cancers. We have
      identified the protein tyrosine phosphatase PTPRO as a regulator of three
      dimensional epithelial morphogenesis of mammary epithelial cells and as a
      regulator of ErbB2-mediated transformation. In addition, we demonstrated that
      ErbB2 is a direct substrate of PTPRO and that decreased expression of PTPRO
      predicts poor prognosis for ErbB2-positive breast cancer patients. Thus, our
      results identify PTPRO as a novel regulator of mammary epithelial transformation,
      a potential tumor suppressor, and a predictive biomarker for breast cancer.

PMID- 22851701
TI  - Gendered spaces, gendered pages: Union women in Civil War nurse narratives.
AB  - This interdisciplinary analysis joins literary and culture studies with history
      using Daphne Spain's theory of gendered spaces. Specifically, we examine the
      reconfiguration of the spaces of military medical work and of book publishing
      that produced popular literary representations of those medical spaces. As a
      social historian of nursing and a scholar of American literature and culture, we
      argue that the examination of Civil War narratives by or about Northern female
      nurses surveys a landscape in which women penetrated the masculine spaces of the
      military hospital and the literary spaces of the wartime narrative. In so doing,
      these women transformed these spaces into places acknowledging and even relying
      upon what had been traditionally considered male domains. Like many
      historiographical papers written about nurses and the impact of their practice
      over time, this work is relevant to those practicing nursing today, specifically
      those issues related to professional authority and professional autonomy.

PMID- 22851699
TI  - FHL2 binds calcineurin and represses pathological cardiac growth.
AB  - Stress-induced hypertrophic growth of the heart predisposes the heart to
      arrhythmia, contractile dysfunction, and clinical heart failure. FHL2 (four-and-a
      half LIM domain protein 2) is expressed predominantly in the heart, and
      inactivation of the gene coding for FHL2 leads to exaggerated responsiveness to
      adrenergic stress. Activation of calcineurin occurs downstream of beta-adrenergic
      signaling and is required for isoproterenol-induced myocardial hypertrophy. Based
      on these facts, we hypothesized that FHL2 suppresses stress-induced activation of
      calcineurin. FHL2 is upregulated in mouse hearts exposed to isoproterenol, a beta
      adrenergic agonist, and isoproterenol-induced increases in the NFAT target genes
      RCAN1.4 and BNP were amplified significantly in FHL2 knockout (FHL2(-/-)) mice
      compared with levels in wild-type (WT) mice. To determine whether the effect of
      FHL2 on NFAT target gene transcript levels occurred at the level of
      transcription, HEK 293 cells and neonatal rat ventricular myocytes (NRVMs) were
      transfected with a luciferase reporter construct harboring the NFAT-dependent
      promoters of either RCAN1 or interleukin 2 (IL-2). Consistent with the in vivo
      data, small interfering RNA (siRNA) knockdown of FHL2 led to increased activation
      of these promoters by constitutively active calcineurin or the calcium ionophore
      ionomycin. Importantly, activation of the RCAN1 promoter by ionomycin, in control
      and FHL2 knockdown cells, was abolished by the calcineurin inhibitor
      cyclosporine, confirming the calcineurin dependence of the response.
      Overexpression of FHL2 inhibited activation of both NFAT reporter constructs.
      Furthermore, NRVMs overexpressing FHL2 exhibited reduced hypertrophic growth in
      response to constitutively active calcineurin, as measured by cell cross
      sectional area and fetal gene expression. Finally, immunostaining in isolated
      adult cardiomyocytes revealed colocalization of FHL2 and calcineurin
      predominantly at the sarcomere and activation of calcineurin by endothelin-1
      facilitated interaction between FHL2 and calcineurin. FHL2 is an endogenous,
      agonist-dependent suppressor of calcineurin.

PMID- 22851700
TI  - Autonomic markers and cardiovascular and arrhythmic events in heart failure
      patients: still a place in prognostication? Data from the GISSI-HF trial.
AB  - AIMS: To investigate the prognostic value of autonomic variables in patients with
      symptomatic chronic heart failure (HF) treated according to current
      recommendations. METHODS AND RESULTS: We analysed 24 h time-domain [standard
      deviation of all normal-to-normal RR intervals (SDNN)], frequency-domain [very
      low frequency and low frequency power (VFLP and LFP)], and non-linear [detrended
      fluctuation analysis (DFA)] heart rate variability, deceleration capacity (DC),
      and heart rate turbulence (HRT) in 388 sinus rhythm HF patients enrolled in the
      GISSI-HF Holter substudy [82% males, age 65 +/-10 years, New York Heart
      Association (NYHA) functional class III-IV 20%, left ventricular ejection
      fraction (LVEF) 33 +/-8%]. Cardiovascular (CV) mortality and combined sudden
      death + implantable cardioverter defibrillator (ICD) discharge were assessed as a
      function of continuous variables in the entire population and in patients with
      LVEF >30% in univariate and multivariable Cox proportional hazards models. After
      a median of 47 months, 57 patients died of CV causes and 47 experienced the
      arrhythmic endpoint. For CV mortality, VLFP, LFP, and turbulence slope (TS)
      improved predictive discrimination (c-index) and risk classification [integrated
      discrimination improvement (IDI)] when added to clinical variables [age >=70
      years, LVEF, non-sustained ventricular tachycardia (NSVT), serum creatinine],
      while for arrhythmic mortality although the c-index increased in all three
      autonomic markers, the results of the IDI were statistically significant only for
      TS when added to NSVT, serum creatinine, and ischaemic aetiology. In 194 patients
      with LVEF >30% (20 arrhythmic events), the hazard ratio of an impaired TS (<2.5
      msper RR interval) was 3.81 (95% confidence interval 1.35-10.7,P = 0.012) after
      adjustment for serum creatinine. CONCLUSIONS: Autonomic indexes still have
      independent predictive value on long-term outcome in HF patients. HRT may help in
      identifying patients with LVEF >30% at increased arrhythmic risk. Trial
      registration NCT00336336.

PMID- 22851702
TI  - Balancing duties to the court and client: the removal of immunity from suit of
      expert witnesses: Jones v Kaney [2011] UKSC 13.

PMID- 22851703
TI  - Stress levels of glucocorticoids inhibit LHbeta-subunit gene expression in
      gonadotrope cells.
AB  - Increased glucocorticoid secretion is a common response to stress and has been
      implicated as a mediator of reproductive suppression upon the pituitary gland. We
      utilized complementary in vitro and in vivo approaches in the mouse to
      investigate the role of glucocorticoids as a stress-induced intermediate capable
      of gonadotrope suppression. Repeated daily restraint stress lengthened the
      ovulatory cycle of female mice and acutely reduced GnRH-induced LH secretion and
      synthesis of LH beta-subunit (LHbeta) mRNA, coincident with increased circulating
      glucocorticoids. Administration of a stress level of glucocorticoid, in the
      absence of stress, blunted LH secretion in ovariectomized female mice,
      demonstrating direct impairment of reproductive function by glucocorticoids.
      Supporting a pituitary action, glucocorticoid receptor (GR) is expressed in mouse
      gonadotropes and treatment with glucocorticoids reduces GnRH-induced LHbeta
      expression in immortalized mouse gonadotrope cells. Analyses revealed that
      glucocorticoid repression localizes to a region of the LHbeta proximal promoter,
      which contains early growth response factor 1 (Egr1) and steroidogenic factor 1
      sites critical for GnRH induction. GR is recruited to this promoter region in the
      presence of GnRH, but not by dexamethasone alone, confirming the necessity of the
      GnRH response for GR repression. In lieu of GnRH, Egr1 induction is sufficient
      for glucocorticoid repression of LHbeta expression, which occurs via GR acting in
      a DNA- and dimerization-independent manner. Collectively, these results expose
      the gonadotrope as an important neuroendocrine site impaired during stress, by
      revealing a molecular mechanism involving Egr1 as a critical integrator of
      complex formation on the LHbeta promoter during GnRH induction and GR repression.

PMID- 22851704
TI  - Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent
      innate allergic inflammation in the lung.
AB  - Chitin exposure in the lung induces eosinophilia and alternative activation of
      macrophages and is correlated with allergic airway disease. However, the
      mechanism underlying chitin-induced polarization of macrophages is poorly
      understood. In this paper, we show that chitin induces alternative activation of
      macrophages in vivo but does not do so directly in vitro. We further show that
      airway epithelial cells bind chitin in vitro and produce CCL2 in response to
      chitin both in vitro and in vivo. Supernatants of chitin-exposed epithelial cells
      promoted alternative activation of macrophages in vitro, whereas Ab
      neutralization of CCL2 in the supernate abolished the alternative activation of
      macrophages. CCL2 acted redundantly in vivo, but mice lacking the CCL2 receptor,
      CCR2, showed impaired alternative activation of macrophages in response to
      chitin, as measured by arginase I, CCL17, and CCL22 expression. Furthermore, CCR2
      knockout mice exposed to chitin had diminished reactive oxygen species products
      in the lung, blunted eosinophil and monocyte recruitment, and impaired eosinophil
      functions as measured by expression of CCL5, IL-13, and CCL11. Thus, airway
      epithelial cells secrete CCL2 in response to chitin and CCR2 signaling mediates
      chitin-induced alternative activation of macrophages and allergic inflammation in
      vivo.

PMID- 22851705
TI  - The role of properdin in zymosan- and Escherichia coli-induced complement
      activation.
AB  - Properdin is well known as an enhancer of the alternative complement
      amplification loop when C3 is activated, whereas its role as a recognition
      molecule of exogenous pathogen-associated molecular patterns and initiator of
      complement activation is less understood. We therefore studied the role of
      properdin in activation of complement in normal human serum by zymosan and
      various Escherichia coli strains. In ELISA, microtiter plates coated with zymosan
      induced efficient complement activation with deposition of C4b and terminal
      complement complex on the solid phase. Virtually no deposition of C4b or terminal
      complement complex was observed with mannose-binding lectin (MBL)-deficient
      serum. Reconstitution with purified MBL showed distinct activation in both
      readouts. In ELISA, normal human serum-induced deposition of properdin by zymosan
      was abolished by the C3-inhibiting peptide compstatin. Flow cytometry was used to
      further explore whether properdin acts as an initial recognition molecule
      reacting directly with zymosan and three E. coli strains. Experiments reported by
      other authors were made with EGTA Mg2+ buffer, permitting autoactivation of C3.
      We found inhibition by compstatin on these substrates, indicating that properdin
      deposition depended on initial C3b deposition followed by properdin in a second
      step. Properdin released from human polymorphonuclear cells stimulated with PMA
      did not bind to zymosan or E. coli, but when incubated in properdin-depleted
      serum this form of properdin bound efficiently to both substrates in a strictly
      C3-dependent manner, as the binding was abolished by compstatin. Collectively,
      these data indicate that properdin in serum as well as polymorphonuclear-released
      properdin is unable to bind and initiate direct alternative pathway activation on
      these substrates.

PMID- 22851706
TI  - Cutting edge: influence of Tmevpg1, a long intergenic noncoding RNA, on the
      expression of Ifng by Th1 cells.
AB  - The majority of the genome is noncoding and was thought to be nonfunctional.
      However, it is now appreciated that transcriptional control of protein coding
      genes resides within these noncoding regions. Thousands of genes encoding long
      intergenic noncoding RNAs (lincRNAs) have been recently identified throughout the
      genome, which positively or negatively regulate transcription of neighboring
      target genes. Both TMEVPG1 and its mouse ortholog encode lincRNAs and are
      positioned near the IFN-gamma gene (IFNG). In this study, we show that
      transcription of both mouse and human TMEVPG1 genes is Th1 selective and
      dependent on Stat4 and T-bet, transcription factors that drive the Th1
      differentiation program. Ifng expression is partially restored in Stat4-/-Tbx21-/
      cells through coexpression of T-bet and Tmevpg1, and Tmevpg1 expression
      contributes to, but alone is not sufficient to, drive Th1-dependent Ifng
      expression. Our results suggest that TMEVPG1 belongs to the general class of
      lincRNAs that positively regulate gene transcription.

PMID- 22851707
TI  - Endothelial cells and fibroblasts amplify the arthritogenic type I IFN response
      in murine Lyme disease and are major sources of chemokines in Borrelia
      burgdorferi-infected joint tissue.
AB  - Localized elevation in type I IFN has been uniquely linked to the severe Lyme
      arthritis that develops in C3H mice infected with the spirochete Borrelia
      burgdorferi. In this study, the dynamic interactions that result in generation of
      these responses were further examined in C3H mice carrying the type I IFN
      receptor gene ablation, which effectively blocks all autocrine/paracrine
      signaling crucial to induction of downstream effectors. Reciprocal radiation
      chimeras between C3H and IFNAR1-/- mice implicated both radiation-sensitive and
      radiation-resistant cells of the joint tissue in the proarthritic induction of
      type I IFN. Ex vivo analysis of cells from the naive joint revealed CD45+ cells
      residing in the tissue to be uniquely capable of initiating the type I IFN
      response to B. burgdorferi. Type I IFN responses were analyzed in real time by
      lineage sorting of cells from infected joint tissue. This demonstrated that
      myeloid cells, endothelial cells, and fibroblasts were responsible for
      propagating the robust IFN response, which peaked at day 7 postinfection and
      rapidly resolved. Endothelial cells and fibroblasts were the dominant sources of
      IFN signature transcripts in the joint tissue. Fibroblasts were also the major
      early source of chemokines associated with polymorphonuclear leukocyte and
      monocyte/macrophage infiltration, thus providing a focal point for arthritis
      development. These findings suggest joint-localized interactions among related
      and unrelated stromal, endothelial, and myeloid cell lineages that may be broadly
      applicable to understanding the pathogeneses of diseases associated with type I
      IFN signature, including systemic lupus erythematosus and some rheumatoid
      arthritides.

PMID- 22851708
TI  - Human H-ficolin inhibits replication of seasonal and pandemic influenza A
      viruses.
AB  - The collectins have been shown to have a role in host defense against influenza A
      virus (IAV) and other significant viral pathogens (e.g., HIV). The ficolins are a
      related group of innate immune proteins that are present at relatively high
      concentrations in serum, but also in respiratory secretions; however, there has
      been little study of the role of ficolins in viral infection. In this study, we
      demonstrate that purified recombinant human H-ficolin and H-ficolin in human
      serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity
      and hemagglutination activity in vitro. Removal of ficolins from human serum or
      bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV
      did not involve the calcium-dependent lectin activity of H-ficolin. We
      demonstrate that H-ficolin is sialylated and that removal of sialic acid
      abrogates IAV inhibition, while addition of the neuraminidase inhibitor
      oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral
      aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are
      generally not inhibited by the collectins surfactant protein D or mannose binding
      lectin because of a paucity of glycan attachments on the hemagglutinin of these
      strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain
      and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a
      surface coated with IAV. These findings suggest that H-ficolin contributes to
      host defense against IAV.

PMID- 22851709
TI  - An NKp30-based chimeric antigen receptor promotes T cell effector functions and
      antitumor efficacy in vivo.
AB  - NKp30 is a natural cytotoxicity receptor that is expressed on NK cells and
      recognizes B7-H6, which is expressed on several types of tumors but few normal
      cells. To target effector T cells against B7-H6+ tumors, we developed several
      chimeric AgRs (CARs) based on NKp30, which contain the CD28- and/or CD3zeta
      signaling domains with the transmembrane domains from CD3zeta, CD28, or CD8alpha.
      The data show that chimeric NKp30-expressing T cells responded to B7-H6+ tumor
      cells. The NKp30 CAR-expressing T cells produced IFN-gamma and killed B7-H6
      ligand-expressing tumor cells; this response was dependent upon ligand expression
      on target cells but not on MHC expression. PBMC-derived dendritic cells also
      express NKp30 ligands, including immature dendritic cells, and they can stimulate
      NKp30 CAR-bearing T cells to produce IFN-gamma, but to a lesser extent. The
      addition of a CD28-signaling domain significantly enhanced the activity of the
      NKp30 CAR in a PI3K-dependent manner. Adoptive transfer of T cells expressing a
      chimeric NKp30 receptor containing a CD28-signaling domain inhibited the growth
      of a B7-H6-expressing murine lymphoma (RMA/B7-H6) in vivo. Moreover, mice that
      remained tumor-free were resistant to a subsequent challenge with the wild-type
      RMA tumor cells, suggesting the generation of immunity against other tumor Ags.
      Overall, this study demonstrates the specificity and therapeutic potential of
      adoptive immunotherapy with NKp30 CAR-expressing T cells against B7-H6+ tumor
      cells in vivo.

PMID- 22851710
TI  - Increased susceptibility to Salmonella infection in signal regulatory protein
      alpha-deficient mice.
AB  - Recent studies have shed light on the connection between elevated erythropoetin
      production/spleen erythropoiesis and increased susceptibility to Salmonella
      infection. In this article, we provide another mouse model, the SIRPalpha
      deficient (Sirpalpha-/-) mouse, that manifests increased erythropoiesis as well
      as heightened susceptibility to Salmonella infection. Sirpalpha-/- mice succumbed
      to systemic infection with attenuated Salmonella, possessing significantly higher
      bacterial loads in both the spleen and the liver. Moreover, Salmonella-specific
      Ab production and Ag-specific CD4 T cells were reduced in Sirpalpha-/- mice
      compared with wild-type controls. To further characterize the potential mechanism
      underlying SIRPalpha-dependent Ag-specific CD4 T cell priming, we demonstrate
      that lack of SIRPalpha expression on dendritic cells results in less efficient Ag
      processing and presentation in vitro. Collectively, these findings demonstrate an
      indispensable role of SIRPalpha for protective immunity to Salmonella infection.

PMID- 22851712
TI  - Differential interaction of the two related fungal species Candida albicans and
      Candida dubliniensis with human neutrophils.
AB  - Candida albicans, the most common facultative human pathogenic fungus is of major
      medical importance, whereas the closely related species Candida dubliniensis is
      less virulent and rarely causes life-threatening, systemic infections. Little is
      known, however, about the reasons for this difference in pathogenicity, and
      especially on the interactions of C. dubliniensis with the human immune system.
      Because innate immunity and, in particular, neutrophil granulocytes play a major
      role in host antifungal defense, we studied the responses of human neutrophils to
      clinical isolates of both C. albicans and C. dubliniensis. C. dubliniensis was
      found to support neutrophil migration and fungal cell uptake to a greater extent
      in comparison with C. albicans, whereas inducing less neutrophil damage and
      extracellular trap formation. The production of antimicrobial reactive oxygen
      species, myeloperoxidase, and lactoferrin, as well as the inflammatory chemokine
      IL-8 by neutrophils was increased when stimulated with C. dubliniensis as
      compared with C. albicans. However, most of the analyzed macrophage-derived
      inflammatory and regulatory cytokines and chemokines, such as IL-1alpha, IL
      1beta, IL-1ra, TNF-alpha, IL-10, G-CSF, and GM-CSF, were less induced by C.
      dubliniensis. Similarly, the amounts of the antifungal immunity-related IL-17A
      produced by PBMCs was significantly lower when challenged with C. dubliniensis
      than with C. albicans. These data indicate that C. dubliniensis triggers stronger
      early neutrophil responses than C. albicans, thus providing insight into the
      differential virulence of these two closely related fungal species, and suggest
      that this is, in part, due to their differential capacity to form hyphae.

PMID- 22851711
TI  - Sialoadhesin promotes rapid proinflammatory and type I IFN responses to a
      sialylated pathogen, Campylobacter jejuni.
AB  - Sialoadhesin (Sn) is a macrophage (Mphi)-restricted receptor that recognizes
      sialylated ligands on host cells and pathogens. Although Sn is thought to be
      important in cellular interactions of Mphis with cells of the immune system, the
      functional consequences of pathogen engagement by Sn are unclear. As a model
      system, we have investigated the role of Sn in Mphi interactions with heat-killed
      Campylobacter jejuni expressing a GD1a-like, sialylated glycan. Compared to Sn
      expressing bone marrow-derived macrophages (BMDM) from wild-type mice, BMDM from
      mice either deficient in Sn or expressing a non-glycan-binding form of Sn showed
      greatly reduced phagocytosis of sialylated C. jejuni. This was accompanied by a
      strong reduction in MyD88-dependent secretion of TNF-alpha, IL-6, IL-12, and IL
      10. In vivo studies demonstrated that functional Sn was required for rapid TNF
      alpha and IFN-beta responses to i.v.-injected sialylated C. jejuni. Bacteria were
      captured within minutes after i.v. injection and were associated with Mphis in
      both liver and spleen. In the spleen, IFN-beta-reactive cells were localized to
      Sn+ Mphis and other cells in the red pulp and marginal zone. Together, these
      studies demonstrate that Sn plays a key role in capturing sialylated pathogens
      and promoting rapid proinflammatory cytokine and type I IFN responses.

PMID- 22851714
TI  - Structure-activity relationship of fenamates as Slo2.1 channel activators.
AB  - Niflumic acid, 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid
      (NFA), a nonsteroidal anti-inflammatory drug that blocks cyclooxygenase (COX),
      was shown previously to activate [Na(+)](i)-regulated Slo2.1 channels. In this
      study, we report that other fenamates, including flufenamic acid, mefenamic acid,
      tolfenamic acid, meclofenamic acid, and a phenyl acetic acid derivative,
      diclofenac, also are low-potency (EC(50) = 80 MUM to 2.1 mM), partial agonists of
      human Slo2.1 channels heterologously expressed in Xenopus oocytes. Substituent
      analysis determined that N-phenylanthranilic acid was the minimal pharmacophore
      for fenamate activation of Slo2.1 channels. The effects of fenamates were
      biphasic, with an initial rapid activation phase followed by a slow phase of
      current inhibition. Ibuprofen, a structurally dissimilar COX inhibitor, did not
      activate Slo2.1. Preincubation of oocytes with ibuprofen did not significantly
      alter the effects of NFA, suggesting that neither channel activation nor
      inhibition is associated with COX activity. A point mutation (A278R) in the pore
      lining S6 segment of Slo2.1 increased the sensitivity to activation and reduced
      the inhibition induced by NFA. Together, our results suggest that fenamates bind
      to two sites on Slo2.1 channels: an extracellular accessible site to activate and
      a cytoplasmic accessible site in the pore to inhibit currents.

PMID- 22851713
TI  - ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during
      B cell differentiation to plasma cells.
AB  - CIITA and MHC class II expression is silenced during the differentiation of B
      cells to plasma cells. When B cell differentiation is carried out ex vivo, CIITA
      silencing occurs rapidly, but the factors contributing to this event are not
      known. ZBTB32, also known as repressor of GATA3, was identified as an early
      repressor of CIITA in an ex vivo plasma cell differentiation model. ZBTB32
      activity occurred at a time when B lymphocyte-induced maturation protein-1 (Blimp
      1), the regulator of plasma cell fate and suppressor of CIITA, was minimally
      induced. Ectopic expression of ZBTB32 suppressed CIITA and I-A gene expression in
      B cells. Short hairpin RNA depletion of ZBTB32 in a plasma cell line resulted in
      re-expression of CIITA and I-A. Compared with conditional Blimp-1 knockout and
      wild-type B cells, B cells from ZBTB32/ROG-knockout mice displayed delayed
      kinetics in silencing CIITA during ex vivo plasma cell differentiation. ZBTB32
      was found to bind to the CIITA gene, suggesting that ZBTB32 directly regulates
      CIITA. Lastly, ZBTB32 and Blimp-1 coimmunoprecipitated, suggesting that the two
      repressors may ultimately function together to silence CIITA expression. These
      results introduce ZBTB32 as a novel regulator of MHC-II gene expression and a
      potential regulatory partner of Blimp-1 in repressing gene expression.

PMID- 22851715
TI  - Molecular mechanisms of chloroquine inhibition of heterologously expressed
      Kir6.2/SUR2A channels.
AB  - Chloroquine and related compounds can inhibit inwardly rectifying potassium
      channels by multiple potential mechanisms, including pore block and allosteric
      effects on channel gating. Motivated by reports that chloroquine inhibition of
      cardiac ATP-sensitive inward rectifier K(+) current (I(KATP)) is antifibrillatory
      in rabbit ventricle, we investigated the mechanism of chloroquine inhibition of
      ATP-sensitive potassium (K(ATP)) channels (Kir6.2/SUR2A) expressed in human
      embryonic kidney 293 cells, using inside-out patch-clamp recordings. We found
      that chloroquine inhibits the Kir6.2/SUR2A channel by interacting with at least
      two different sites and by two mechanisms of action. A fast-onset effect is
      observed at depolarized membrane voltages and enhanced by the N160D mutation in
      the central cavity, probably reflecting direct channel block resulting from the
      drug entering the channel pore from the cytoplasmic side. Conversely, a slow
      onset, voltage-independent inhibition of I(KATP) is regulated by chloroquine
      interaction with a different site and probably involves disruption of
      interactions between Kir6.2/SUR2A and phosphatidylinositol 4,5-bisphosphate. Our
      findings reveal multiple mechanisms of K(ATP) channel inhibition by chloroquine,
      highlighting the numerous convergent regulatory mechanisms of these ligand
      dependent ion channels.

PMID- 22851717
TI  - Simple adaptations to the Templeton model for IVF outcome prediction make it
      current and clinically useful.
AB  - STUDY QUESTION: What is the validity of the Templeton model (TM) in predicting
      live birth (LB) for a couple starting an IVF/ICSI cycle? SUMMARY ANSWER: A centre
      specific model based on the original predictors of the TM may reach a sufficient
      level of accuracy to be used in every day practice, with a few simple
      adaptations. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The TM seems the best
      predictive model of LB in IVF. However, previous validations of the TM suggest a
      lack of discrimination and calibration which means that it is not used in regular
      practice. We confirm this finding, and argue that such results are predictable,
      and essentially due to a strong centre effect. We provide evidence that the TM
      constitutes a useful reference reflecting a high proportion of the patient-mix
      effect since the parameters of the model remain invariant among centres, but also
      across various cultures, countries and types of hospitals. The only difference
      was the intercept value, interpreted as the measurement of the global performance
      of one centre, in particular, for a population of reference. STUDY DESIGN: The
      validity of the TM was tested by a retrospective analysis all IVF/ICSI cycles (n
      = 12 901) in our centre since 2000. PARTICIPANTS, SETTING AND METHODS: All
      IVF/ICSI cycles were included in the analysis. The model discrimination was
      evaluated by C-statistics, calculated as the area under the curve of an ROC
      curve. The TM was then adjusted for our data and additional variables were
      assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Poor calibration and
      discrimination (C = 0.64) was observed in conformity with previous external
      validations. Fitting the TM to our centre constituted the first substantial
      improvement in prediction accuracy of discrimination (C = 0.69) and calibration.
      We identified an important linear time trend effect and the added value of three
      other predictors (FSH, smoking habits and BMI) that significantly improved the
      model (C = 0.71). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Bias due to
      missing data handling was assessed through sensitivity analyses. GENERALIZABILITY
      TO OTHER POPULATIONS: Neither the TM nor any other models based on some centres
      are directly applicable to other centres. However, the TM constitutes a useful
      basis to build an accurate centre-specific model. STUDY FUNDING/COMPETING
      INTEREST(S): There were no commercial relationships (i.e. consultancies, patent
      licensing agreements) that might pose a conflict of interest in connection with
      the submitted manuscript. The objective of this research was not directed toward
      any treatment effects.

PMID- 22851716
TI  - P6981, an arylstibonic acid, is a novel low nanomolar inhibitor of cAMP response
      element-binding protein binding to DNA.
AB  - Several basic leucine zipper (B-ZIP) transcription factors have been implicated
      in cancer, substance abuse, and other pathological conditions. We previously
      identified arylstibonic acids that bind to B-ZIP proteins and inhibit their
      interaction with DNA. In this study, we used electrophoretic mobility shift assay
      to analyze 46 arylstibonic acids for their activity to disrupt the DNA binding of
      three B-ZIP [CCAAT/enhancer-binding protein alpha, cyclic AMP-response element
      binding protein (CREB), and vitellogenin gene-binding protein (VBP)] and two
      basic helix-loop-helix leucine zipper (B-HLH-ZIP) [USF (upstream stimulating
      factor) and Mitf] proteins. Twenty-five arylstibonic acids showed activity at
      micromolar concentrations. The most active compound, P6981 [2-(3
      stibonophenyl)malonic acid], had half-maximal inhibition at ~5 nM for CREB.
      Circular dichroism thermal denaturation studies indicated that P6981 binds both
      the B-ZIP domain and the leucine zipper. The crystal structure of an arylstibonic
      acid, NSC13778, bound to the VBP leucine zipper identified electrostatic
      interactions between both the stibonic and carboxylic acid groups of NSC13778
      [(E)-3-(3-stibonophenyl)acrylic acid] and arginine side chains of VBP, which is
      also involved in interhelical salt bridges in the leucine zipper. P6981 induced
      GFP-B-ZIP chimeric proteins to partially localize to the cytoplasm, demonstrating
      that it is active in cells. P6981 inhibited the growth of a patient-derived clear
      cell sarcoma cell line whose oncogenic potential is driven by a chimeric protein
      EWS-ATF1 (Ewing's sarcoma protein-activating transcription factor 1), which
      contains the DNA binding domain of ATF1, a B-ZIP protein. NSC13778 inhibited the
      growth of xenografted clear cell sarcoma, and no toxicity was observed. These
      experiments suggest that antimony containing arylstibonic acids are promising
      leads for suppression of DNA binding activities of B-ZIP and B-HLH-ZIP
      transcription factors.

PMID- 22851718
TI  - Integration of patient characteristics and the results of Chlamydia antibody
      testing and hysterosalpingography in the diagnosis of tubal pathology: an
      individual patient data meta-analysis.
AB  - BACKGROUND: Tubal patency tests are routinely performed in the diagnostic work-up
      of subfertile patients, but it is unknown whether these diagnostic tests add
      value beyond the information obtained by medical history taking and findings at
      physical examination. We used individual patient data meta-analysis to assess
      this question. METHODS: We approached authors of primary studies for data sets
      containing information on patient characteristics and results from tubal patency
      tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and
      laparoscopy. We used logistic regression to create models that predict tubal
      pathology from medical history and physical examination alone, as well as models
      in which the results of tubal patency tests are integrated in the patient
      characteristics model. Laparoscopy was considered to be the reference test.
      RESULTS: We obtained data from four studies reporting on 4883 women. The duration
      of subfertility, number of previous pregnancies and a history of previous pelvic
      inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for
      the patient characteristics model. This model showed an area under the receiver
      operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) 0.61
      0.65]. For any tubal pathology, the addition of HSG significantly improved the
      predictive performance to an AUC of 0.74 (95% CI 0.73-0.76) (P < 0.001). For
      bilateral tubal pathology, the addition of both CAT and HSG increased the
      predictive performance to an AUC of 0.76 (95% CI 0.74-0.79). CONCLUSIONS: In the
      work-up for subfertile couples, the combination of patient characteristics with
      CAT and HSG results gives the best diagnostic performance for the diagnosis of
      bilateral tubal pathology.

PMID- 22851719
TI  - Epidural and brain abscess following Pearl Spot fish bone injury.

PMID- 22851720
TI  - Cognitive decline after hospitalization in a community population of older
      persons.

PMID- 22851721
TI  - Predicting outcome of IV thrombolysis-treated ischemic stroke patients: the
      DRAGON score.

PMID- 22851722
TI  - Pearls & oy-sters: the use of CT venography in Hirayama disease.

PMID- 22851723
TI  - Clinical reasoning: agitation and psychosis in a patient after renal
      transplantation.

PMID- 22851725
TI  - Teaching NeuroImages: unilateral arm and contralateral leg amyotrophy in FSHD:
      unusual presentation.

PMID- 22851726
TI  - Multiple sclerosis and stress.

PMID- 22851727
TI  - Upper airway symptoms among workers with work-related respiratory complaints.
AB  - BACKGROUND: Work-related rhinitis and asthma symptoms frequently co-exist. AIMS:
      To determine the prevalence and nature of nasal, pharyngeal, laryngeal and sinus
      symptoms among individuals with work-related respiratory symptoms. METHODS:
      Individuals referred to a tertiary occupational asthma clinic for investigations
      with specific inhalation challenges were evaluated using the RHINASTHMA quality
      of life questionnaire and a questionnaire that assessed the nature and frequency
      of upper airway symptoms, their relationship to the workplace and their temporal
      relationship with the onset of asthma symptoms. RESULTS: There were 83 study
      participants. At least one upper airway symptom was reported by all of these
      individuals: nasal in 92%; pharyngeal in 82%; laryngeal in 65% and sinus in 53%
      of participants. Overall, there were no significant differences in the
      frequencies of nasal, pharyngeal, laryngeal and sinus symptoms when comparing
      these with occupational asthma (OA), work-exacerbated asthma (WEA) and work
      related respiratory symptoms (WRS), except that nasal bleeding was most frequent
      among those with WRS. The presence of laryngeal symptoms was significantly
      associated with rhinitis-specific quality of life impairment. Individuals with
      workplace exposures to high molecular weight agents had greater impaired quality
      of life than those who were exposed to low molecular weight agents (RHINASTMA
      Upper Airway sub-scores: 24.0+/-10.4 versus 19.8+/-6.8; P < 0.05). CONCLUSIONS:
      Individuals who were referred for work-related respiratory symptoms experienced
      high rates of work-related nasal, pharyngeal, laryngeal and sinus symptoms,
      regardless of having OA, WEA or WRS.

PMID- 22851728
TI  - Renal denervation: ultima ratio or standard in treatment-resistant hypertension.

PMID- 22851729
TI  - Management of antiangiogenic therapy-induced hypertension.

PMID- 22851730
TI  - Direct recording of renal sympathetic nerve activity in unrestrained, conscious
      mice.
AB  - Renal sympathetic nerve activity (RSNA) has been measured in anesthetized mice.
      However, anesthesia and acute surgical preparation cause poor cardiovascular
      stability and unphysiological blood pressures. This compromised physiological
      state confounds proper interpretation of experimental results considering the
      inseparable link between cardiovascular status and autonomic nervous tone. We,
      therefore, developed a surgical and experimental protocol for measuring RSNA in
      conscious, unrestrained mice. Male C57Bl/6J mice were chronically instrumented
      with blood pressure radiotelemeters, an indwelling jugular venous catheter and a
      bipolar electrode for recording RSNA. Mice were placed in a home cage and left to
      recover for 48 to 72 hours. Survival rate was 100%; all of the mice exhibited
      normal behavior with no sign of distress 24 hours after surgery. RSNA was
      successfully recorded in 80% of the mice at 48 and 72 hours postsurgery; viable
      RSNA was reduced to 70% and 50% at 4 and 5 days postsurgery, respectively. Mean
      arterial pressure (116+/-2 mm Hg; n=10) was consistent with values reported
      previously for conscious mice. RSNA increased with the normal physical activities
      of eating and grooming and was validated by ganglionic blockade and
      pharmacological manipulation of blood pressure; reduction in blood pressure to
      62+/-3 mm Hg with nitroprusside increased RSNA by 77+/-9% above baseline (n=5;
      P<0.05), whereas an increase in blood pressure to 137+/-6 mm Hg with
      phenylephrine reduced RSNA by 79+/-2% compared with baseline (n=5; P<0.05). Thus,
      we demonstrate an accessible and effective method for direct assessment of RSNA
      in conscious, unrestrained mice.

PMID- 22851731
TI  - The phosphorylated sodium chloride cotransporter in urinary exosomes is superior
      to prostasin as a marker for aldosteronism.
AB  - Urinary exosomes are vesicles derived from renal tubular epithelial cells.
      Exosomes often contain several disease-associated proteins and are thus useful
      targets for identifying biomarkers of disease. Here, we hypothesized that the
      phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or
      prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal
      models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients
      with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or
      spot urine using ultracentrifugation. In rats, a normal or a high dose of
      aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes (P<0.05
      for all). A low-sodium diet also increased pNCC in urinary exosomes approximately
      1.5-fold after 4 and after 8 days of treatment. The effects of these maneuvers on
      prostasin in urinary exosomes were less clear, showing a significant 1.5-fold
      increase only after 2 and 3 days of high-aldosterone infusion. In urinary
      exosomes of patients with primary aldosteronism, pNCC was 2.6-fold higher
      (P<0.05) while prostasin was 1.5-fold higher (P=0.07) than in patients with
      essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin
      are promising markers for aldosteronism in experimental animals and patients.
      These markers may be used to assess the biological activity of aldosterone and,
      potentially, as clinical biomarkers for primary aldosteronism.

PMID- 22851732
TI  - Associations of bisphenol A exposure with heart rate variability and blood
      pressure.
AB  - Bisphenol A (BPA) is a high-volume production chemical that has been suspected to
      have adverse health effects. Recent studies have suggested that cardiovascular
      diseases are associated with the BPA exposure. The aim of present study was to
      investigate the associations of urinary BPA with heart rate variability and blood
      pressure. We recruited 560 noninstitutionalized elderly citizens from August 2008
      to August 2010 in Seoul. All of the participants were >=60 years old. The
      participants took medical examinations <=5 times. Urinary BPA concentration,
      heart rate variability, and blood pressure were measured at each time. A total of
      1511 observations from 521 participants were included in the analyses. We
      observed that urinary BPA was associated negatively with the root mean square of
      successive differences for heart rate and positively with blood pressure. The
      odds ratio of showing hypertension (systolic blood pressure >=140 mm Hg or
      diastolic blood pressure >=90 mm Hg) was 1.27 (95% CI, 0.85-1.88) in the fourth
      quartile compared with the first quartile of urinary BPA concentration. When the
      analyses were restricted to participants who did not report previous history of
      hypertension (n=258), the odds ratio was increased to 2.35 (95% CI, 1.33-4.17).

PMID- 22851733
TI  - Relationship between on-treatment decreases in inappropriate versus absolute or
      indexed left ventricular mass and increases in ejection fraction in hypertension.
AB  - Although in cross-sectional studies left ventricular mass (LVM), which exceeds
      that predicted by workload (inappropriate LVM [LVM(inappr)]) but not absolute LVM
      or LVM index (LVMI), is inversely related to LV ejection fraction (EF), whether
      on-treatment decreases in LVM(inappr) (%observed/predicted LVM) account for
      increases in EF beyond LVM or LVMI is unclear. Echocardiography was performed in
      168 mild-to-moderate hypertensives treated for 4 months. Although in patients
      with an LVMI >51 g/m(2.7) (n=112; change in LVMI, -13.7+/-14.0 g/m(2.7);
      P<0.0001) but not in patients with an LVMI <=51 g/m(2.7) (n=56; change in LVMI,
      1.3+/-9.3 g/m(2.7)) LVMI decreased with treatment, treatment failed to increase
      EF in either group (1.2+/-10.8% and 2.7+/-10.7%, respectively). In contrast, in
      patients with inappropriate LV hypertrophy (LVM(inappr) >150%; n=33) LVM(inappr)
      decreased (-32+/-27%; P<0.0001) and EF increased (5.0+/-10.3%; P<0.05) after
      treatment, whereas in patients with an LVM(inappr) <=150% (n=135), neither
      LVM(inappr) (-0.5+/-23%) nor EF (0.9+/-10.3%) changed with therapy. With
      adjustments for circumferential LV wall stress and other confounders, whereas on
      treatment decreases in LVM or LVMI were weakly related to an attenuated EF
      (partial r=0.17; P<0.05), on-treatment decreases in LVM(inappr) were strongly
      related to increases in EF even after further adjustments for LVM or LVMI
      (partial r=-0.63 [CI, -0.71 to -0.52]; P<0.0001). In conclusion, decreases in
      LVM(inappr) are strongly related to on-treatment increases in EF beyond changes
      in LVM and LVMI. LV hypertrophy can, therefore, be viewed as a compensatory
      change that preserves EF, but when in excess of that predicted by stroke work, it
      can be viewed as a pathophysiological process accounting for a reduced EF.

PMID- 22851734
TI  - Protective effects of flavanol-rich dark chocolate on endothelial function and
      wave reflection during acute hyperglycemia.
AB  - Nitric oxide plays a pivotal role in regulating vascular tone. Different studies
      show endothelial function is impaired during hyperglycemia. Dark chocolate
      increases flow-mediated dilation in healthy and hypertensive subjects with and
      without glucose intolerance; however, the effect of pretreatment with dark
      chocolate on endothelial function and other vascular responses to hyperglycemia
      has not been examined. Therefore, we aimed to investigate the effects of flavanol
      rich dark chocolate administration on (1) flow-mediated dilation and wave
      reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and
      after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males,
      28.2+/-2.7 years) randomly received either 100 g/d dark chocolate or flavanol
      free white chocolate for 3 days. After 7 days washout period, volunteers were
      switched to the other treatment. Flow-mediated dilation, stiffness index,
      reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso
      PGF(2alpha) were evaluated after each treatment phase and OGTT. Compared with
      white chocolate, dark chocolate ingestion improved flow-mediated dilation
      (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2alpha) (P<0.05). After
      white chocolate ingestion, flow-mediated dilation was reduced after OGTT from
      7.88+/-0.68 to 6.07+/-0.76 (P=0.027), 6.74+/-0.51 (P=0.046) at 1 and 2 h after
      the glucose load, respectively. Similarly, after white chocolate but not after
      dark chocolate, wave reflections, blood pressure, and endothelin-1 and 8-iso
      PGF(2alpha) increased after OGTT. OGTT causes acute, transient impairment of
      endothelial function and oxidative stress, which is attenuated by flavanol-rich
      dark chocolate. These results suggest cocoa flavanols may contribute to vascular
      health by reducing the postprandial impairment of arterial function associated
      with the pathogenesis of atherosclerosis.

PMID- 22851735
TI  - Is the atherosclerotic risk of extreme dipping in youth partly explained by
      exaggerated morning surge?

PMID- 22851736
TI  - Stem cell antigen 1 protects against cardiac hypertrophy and fibrosis after
      pressure overload.
AB  - Stem cell antigen (Sca) 1, a glycosyl phosphatidylinositol-anchored protein
      localized to lipid rafts, is upregulated in the heart during myocardial
      infarction and renovascular hypertension-induced cardiac hypertrophy. It has been
      suggested that Sca-1 plays an important role in myocardial infarction. To
      investigate the role of Sca-1 in cardiac hypertrophy, we performed aortic banding
      in Sca-1 cardiac-specific transgenic mice, Sca-1 knockout mice, and their wild
      type littermates. Cardiac hypertrophy was evaluated by echocardiographic,
      hemodynamic, pathological, and molecular analyses. Sca-1 expression was
      upregulated and detected in cardiomyocytes after aortic banding surgery in wild
      type mice. Sca-1 transgenic mice exhibited significantly attenuated cardiac
      hypertrophy and fibrosis and preserved cardiac function compared with wild-type
      mice after 4 weeks of aortic banding. Conversely, Sca-1 knockout dramatically
      worsened cardiac hypertrophy, fibrosis, and dysfunction after pressure overload.
      Furthermore, aortic banding-induced activation of Src, mitogen-activated protein
      kinases, and Akt was blunted by Sca-1 overexpression and enhanced by Sca-1
      deficiency. Our results suggest that Sca-1 protects against cardiac hypertrophy
      and fibrosis via regulation of multiple pathways in cardiomyocytes.

PMID- 22851737
TI  - Factors affecting work-related shoulder pain.
AB  - BACKGROUND: Work-related shoulder pain is a common problem. Ergonomic factors in
      the workplace are thought to be important but a number of other factors have also
      been associated with shoulder pain. AIMS: To identify risk factors for work
      related shoulder pain in Alberta, focusing particularly on ergonomic risk
      factors. METHODS: A case referent design was used to compare individuals who made
      a Workers' Compensation Board (WCB) claim for work-related shoulder pain with
      individuals who made a claim for other types of injury. Data were collected using
      a postal questionnaire and analysed by logistic regression. RESULTS: There were
      1263 participants (562 cases, 701 referents). The participation rate was 25%
      among cases and 21% among referents (P < 0.01). Factors associated with an
      increased likelihood of claim for shoulder injury included lifting >=10 kg above
      shoulder height for >=15 min per day, shoulder pain in the month prior to injury,
      working in the 'Government, education, and health services' industry sector and
      being occasionally/never satisfied with support from colleagues. CONCLUSIONS:
      These results support the importance of ergonomic factors in work-related
      shoulder pain claims, particularly the lifting of weights above shoulder level
      for even short periods. Relatively simple ergonomic measures, such as restricting
      above shoulder lifting, could be adopted with the aim of reducing the risk of
      shoulder injury at work.

PMID- 22851738
TI  - Educational intervention among farmers in a community health care setting.
AB  - BACKGROUND: Farmers are at increased risk of developing work-related respiratory
      diseases including asthma, but little is known about their occupational health
      and safety (OHS) knowledge and exposure prevention practices. Educational
      interventions may improve knowledge and practice related to prevention. AIMS: To
      determine the feasibility of an educational intervention for farmers in a
      community health centre setting. METHODS: This was a pilot study. Farmers were
      recruited by the community health centre and completed a questionnaire on
      symptoms, OHS knowledge and exposure prevention practices. The intervention group
      received education on work-related asthma and exposure control strategies, and
      was offered spirometry and respirator fit testing. All subjects were asked to
      repeat the questionnaire 6 months later. RESULTS: There were 68 study
      participants of whom 38 formed the intervention group. At baseline, almost 60% of
      farmers reported having received OHS training and were familiar with material
      safety data sheets (MSDSs); fewer (approximately 40%) reported knowledge of OHS
      legislation and availability of MSDSs. Approximately, two-thirds of subjects
      reported using respiratory protection. The response rate for repeating the
      questionnaire was 76% in the intervention group and 77% in the controls. Among
      the intervention subjects, statistically significant increases were observed in
      reported safety training, familiarity and availability of MSDSs and knowledge of
      OHS legislation. CONCLUSIONS: Gaps in OHS knowledge were observed. The
      educational intervention on OHS knowledge and exposure prevention practices in
      the community health centre setting was feasible. Larger, more-controlled studies
      should be undertaken as this study suggests a positive effect on OHS knowledge
      and prevention practices.

PMID- 22851739
TI  - DASH work module in workers with hand-arm vibration syndrome.
AB  - BACKGROUND: The Disabilities of the Arm, Shoulder and Hand work module (DASH-W)
      questionnaire has not previously been described in relation to hand-arm vibration
      syndrome (HAVS). AIMS: To measure work-related disability in workers with HAVS
      using the DASH-W questionnaire and to determine how the various components of
      HAVS affect the DASH-W score. METHODS: Workers with HAVS from a variety of
      industries were assessed over a 2-year period at the occupational health clinic,
      St Michael's Hospital, Toronto. Subjects completed the DASH-W questionnaire and
      were assessed by an occupational physician to determine their Stockholm
      sensorineural and vascular stages and upper extremity pain score measured by the
      Borg scale, as an indication of musculoskeletal problems associated with HAVS.
      The average DASH-W score was compared with the average value for the US
      population. Multiple linear regression was used to determine the contribution of
      the various components of HAVS to the DASH-W score. RESULTS: There were 139 (134
      men and 5 women) participants. The subjects with HAVS had a mean DASH-W score of
      54.7 (95% CI: 50.3-59.1), which was considerably higher than the average for the
      US population (P < 0.001). Statistically significant HAVS variables in the
      multiple linear regression included the Stockholm sensorineural stage (P < 0.05)
      and the upper extremity pain score (P < 0.001) with the pain score having the
      highest partial R (2) value. CONCLUSIONS: Workers with HAVS reported significant
      upper extremity work-related disability as measured by the DASH-W questionnaire,
      and the upper extremity pain score made the largest contribution to the DASH-W
      scores in these subjects.

PMID- 22851740
TI  - Locally derived traffic-related air pollution and fetal growth restriction: a
      retrospective cohort study.
AB  - BACKGROUND: Fetal growth restriction has been inconsistently associated with
      maternal exposure to elevated levels of traffic-related air pollution. OBJECTIVE:
      We investigated the relationship between an individualised measure of fetal
      growth and maternal exposure to a specific marker for traffic-related air
      pollution. METHODS: We estimated maternal residential exposure to a marker for
      traffic-related air pollution (nitrogen dioxide, NO2) during pregnancy for 23,452
      births using temporally adjusted land-use regression. Logistic regression was
      used to investigate associations with small for gestational age and sex (SGA) and
      fetal growth restriction, defined as proportion of optimal birth weight (POBW)
      below the 10th percentile. Sub-populations investigated were: women who spent
      most time at home, women who did not move house, women with respiratory or
      circulatory morbidity, women living in low/middle/high socio-economic areas,
      women who delivered before 37 weeks gestation, and women who delivered from 37
      weeks gestation. RESULTS: An IQR increase in traffic-related air pollution in the
      second trimester across all women was associated with an OR of 1.31 (95% CI 1.07
      to 1.60) for fetal growth restriction. Effects on fetal growth restriction (low
      POBW) were highest among women who subsequently delivered before 37 weeks of
      gestation. Effects on SGA were highest among women who did not move house: OR
      1.35 (95% CI 1.08 to 1.69). CONCLUSIONS: Larger effect sizes were observed for
      low POBW than for SGA. Exposure to traffic-related air pollution in mid to late
      pregnancy was associated with risk of SGA and low POBW in this study.

PMID- 22851741
TI  - Meeting the challenges of infection in pediatric peritoneal dialysis.

PMID- 22851743
TI  - Inhaled anticholinergic agents and acute urinary retention in men with lower
      urinary tract symptoms or benign prostatic hyperplasia.
AB  - OBJECTIVE: To assess the risk of acute urinary retention with the use of inhaled
      anticholinergic agents in men with lower urinary tract symptoms (LUTS) or benign
      prostatic hyperplasia (BPH). DATA SOURCES: A literature search was performed with
      MEDLINE via PubMed from 1967 through May 2012 using the terms inhaled
      anticholinergics, urinary retention, benign prostatic hyperplasia, lower urinary
      tract symptoms, tiotropium, and ipratropium. In addition, references from
      reviewed publications were identified and official labeling was obtained from the
      manufacturers' Web sites. STUDY SELECTION AND DATA EXTRACTION: Only English
      language publications were included. Randomized controlled trial data,
      observational studies, case reports, package labeling, and commentaries regarding
      men with BPH/LUTS using inhaled anticholinergic agents and the associated
      development of urinary retention were reviewed. DATA SYNTHESIS: Two case reports;
      1 prospective, open-label, single-arm study; and 2 nested case-control studies
      evaluated or described the use of inhaled anticholinergic agents and the
      development of acute urinary retention in men with BPH/LUTS. Taken together, the
      available data demonstrate that treatment with inhaled anticholinergic agents is
      associated with acute urinary retention in men with preexisting LUTS or BPH.
      CONCLUSIONS: Men with LUTS or BPH who are treated with inhaled anticholinergic
      agents may develop acute urinary retention, but this cannot be quantified based
      on the limited information available. Inhaled anticholinergic agents should be
      used when indicated in men with LUTS or BPH, but close monitoring and patient
      education should be implemented.

PMID- 22851744
TI  - Competitive advantage of Borrelia burgdorferi with outer surface protein BBA03
      during tick-mediated infection of the mammalian host.
AB  - Linear plasmid lp54 is one of the most highly conserved and differentially
      expressed elements of the segmented genome of the Lyme disease spirochete
      Borrelia burgdorferi. We previously reported that deletion of a 4.1-kb region of
      lp54 (bba01 to bba07 [bba01-bba07]) led to a slight attenuation of tick
      transmitted infection in mice following challenge with a large number of infected
      ticks. In the current study, we reduced the number of ticks in the challenge to
      more closely mimic the natural dose and found a profound defect in tick
      transmitted infection of the bba01-bba07 mutant relative to wild-type B.
      burgdorferi. We next focused on deletion of bba03 as the most likely cause of
      this mutant phenotype, as previous studies have shown that expression of bba03 is
      increased by culture conditions that simulate tick feeding. Consistent with this
      hypothesis, we demonstrated increased expression of bba03 by spirochetes in fed
      relative to unfed ticks. We also observed that a bba03 deletion mutant, although
      fully competent by itself, did not efficiently infect mice when transmitted by
      ticks that were simultaneously coinfected with wild-type B. burgdorferi. These
      results suggest that BBA03 provides a competitive advantage to spirochetes
      carrying this protein during tick transmission to a mammalian host in the natural
      infectious cycle.

PMID- 22851742
TI  - Consensus guidelines for the prevention and treatment of catheter-related
      infections and peritonitis in pediatric patients receiving peritoneal dialysis:
      2012 update.

PMID- 22851745
TI  - Roles of chaperone/usher pathways of Yersinia pestis in a murine model of plague
      and adhesion to host cells.
AB  - Yersinia pestis and many other Gram-negative pathogenic bacteria use the
      chaperone/usher (CU) pathway to assemble virulence-associated surface fibers
      termed pili or fimbriae. Y. pestis has two well-characterized CU pathways: the
      caf genes coding for the F1 capsule and the psa genes coding for the pH 6
      antigen. The Y. pestis genome contains additional CU pathways that are capable of
      assembling pilus fibers, but the roles of these pathways in the pathogenesis of
      plague are not understood. We constructed deletion mutations in the usher genes
      for six of the additional Y. pestis CU pathways. The wild-type (WT) and usher
      deletion strains were compared in the murine bubonic (subcutaneous) and pneumonic
      (intranasal) plague infection models. Y. pestis strains containing deletions in
      CU pathways y0348-0352, y1858-1862, and y1869-1873 were attenuated for virulence
      compared to the WT strain by the intranasal, but not subcutaneous, routes of
      infection, suggesting specific roles for these pathways during pneumonic plague.
      We examined binding of the Y. pestis WT and usher deletion strains to A549 human
      lung epithelial cells, HEp-2 human cervical epithelial cells, and primary human
      and murine macrophages. Y. pestis CU pathways y0348-0352 and y1858-1862 were
      found to contribute to adhesion to all host cells tested, whereas pathway y1869
      1873 was specific for binding to macrophages. The correlation between the
      virulence attenuation and host cell binding phenotypes of the usher deletion
      mutants identifies three of the additional CU pathways of Y. pestis as mediating
      interactions with host cells that are important for the pathogenesis of plague.

PMID- 22851746
TI  - Type 2 innate immunity in helminth infection is induced redundantly and acts
      autonomously following CD11c(+) cell depletion.
AB  - Infection with gastrointestinal helminths generates a dominant type 2 response
      among both adaptive (Th2) and innate (macrophage, eosinophil, and innate
      lymphoid) immune cell types. Two additional innate cell types, CD11c(high)
      dendritic cells (DCs) and basophils, have been implicated in the genesis of type
      2 immunity. Investigating the type 2 response to intestinal nematode parasites,
      including Heligmosomoides polygyrus and Nippostrongylus brasiliensis, we first
      confirmed the requirement for DCs in stimulating Th2 adaptive immunity against
      these helminths through depletion of CD11c(high) cells by administration of
      diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in
      mice depleted of basophils by antibody treatment. Th2 responses can be induced by
      adoptive transfer of DCs, but not basophils, exposed to soluble excretory
      secretory products from these helminths. However, innate type 2 responses arose
      equally strongly in the presence or absence of CD11c(high) cells or basophils;
      thus, in CD11c.DOG mice, the alternative activation of macrophages, as measured
      by expression of arginase-1, RELM-alpha, and Ym-1 (Chi3L3) in the intestine
      following H. polygyrus infection or in the lung following N. brasiliensis
      infection, was unaltered by depletion of CD11c-expressing DCs and alveolar
      macrophages or by antibody-mediated basophil depletion. Similarly, goblet cell
      associated RELM-beta in lung and intestinal tissues, lung eosinophilia, and
      expansion of innate lymphoid ("nuocyte") populations all proceeded irrespective
      of depletion of CD11c(high) cells or basophils. Thus, while CD11c(high) DCs
      initiate helminth-specific adaptive immunity, innate type 2 cells are able to
      mount an autonomous response to the challenge of parasite infection.

PMID- 22851747
TI  - Mycobacterium marinum SecA2 promotes stable granulomas and induces tumor necrosis
      factor alpha in vivo.
AB  - SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, is required
      for translocation of a limited set of proteins across the cytosolic membrane, and
      plays an important role in virulence in several bacteria, including mycobacteria
      that cause diseases such as tuberculosis and leprosy. However, the mechanisms by
      which SecA2 affects virulence are incompletely understood. To investigate whether
      SecA2 modulates host immune responses in vivo, we studied Mycobacterium marinum
      infection in two different hosts: an established zebrafish model and a recently
      described mouse model. Here we show that M. marinum DeltasecA2 was attenuated for
      virulence in both host species and SecA2 was needed for normal granuloma numbers
      and for optimal tumor necrosis factor alpha response in both zebrafish and mice.
      M. marinum DeltasecA2 was more sensitive to SDS and had unique protrusions from
      its cell envelope when examined by cryo-electron tomography, suggesting that
      SecA2 is important for bacterial cell wall integrity. These results provide
      evidence that SecA2 induces granulomas and is required for bacterial modulation
      of the host response because it affects the mycobacterial cell envelope.

PMID- 22851748
TI  - Enterococcus faecalis enhances cell proliferation through hydrogen peroxide
      mediated epidermal growth factor receptor activation.
AB  - Enterococcus faecalis is a member of the intestinal and oral microbiota that may
      affect the etiology of colorectal and oral cancers. The mechanisms by which E.
      faecalis may contribute to the initiation and progression of these cancers remain
      uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to
      play a crucial role in oral carcinogenesis. A link between E. faecalis and EGFR
      signaling in oral cancer has not been elucidated. The present study aimed to
      evaluate the association between E. faecalis and oral cancer and to determine the
      underlying mechanisms that link E. faecalis to EGFR signaling. We report the high
      frequency of E. faecalis infection in oral tumors and the clinical association
      with EGFR activation. Using human oral cancer cells, we support the clinical
      findings and demonstrate that E. faecalis can induce EGFR activation and cell
      proliferation. E. faecalis activates EGFR through production of H(2)O(2), a
      signaling molecule that activates several signaling pathways. Inhibitors of
      H(2)O(2) (catalase) and EGFR (gefitinib) significantly blocked E. faecalis
      induced EGFR activation and cell proliferation. Therefore, E. faecalis infection
      of oral tumor tissues suggests a possible association between E. faecalis
      infection and oral carcinogenesis. Interaction of E. faecalis with host cells and
      production of H(2)O(2) increase EGFR activation, thereby contributing to cell
      proliferation.

PMID- 22851749
TI  - Activation of host mitogen-activated protein kinases by secreted Legionella
      pneumophila effectors that inhibit host protein translation.
AB  - Studies of innate immunity in metazoans have largely focused on detection of
      microbial molecules by host pattern recognition receptors (PRRs). A complementary
      mode of innate immune recognition, based on detection of pathogen-encoded
      activities, has long been recognized in plants, where it is termed effector
      triggered immunity; however, little is known about the possibility of effector
      triggered immunity in metazoans. Legionella pneumophila is an intracellular
      bacterial pathogen that causes Legionnaires' disease, an inflammatory pneumonia.
      We recently demonstrated that macrophages infected with L. pneumophila exhibit
      mitogen-activated protein (MAP) kinase (MAPK) activation that is independent of
      known PRRs but dependent on a functional bacterial secretion system. Here, we
      show that five secreted L. pneumophila effectors are responsible for the
      activation of host MAP kinases. These five effectors inhibit host translation,
      and their activity is required for host MAPK activation. We demonstrate that MAPK
      activation by these effectors shapes the host transcriptional response to L.
      pneumophila. Furthermore, we find that uninfected macrophages treated with two
      different translation inhibitors exhibit activation of MAP kinases and
      upregulation of target genes, indicating that translation inhibition alone is
      sufficient to elicit this response in macrophages. MAP kinase pathways are
      crucial in many aspects of the immune response, including inflammation and cell
      motility. Our results demonstrate that this important host pathway can be
      activated in response to a pathogen-encoded activity, adding to an emerging body
      of evidence in support of this novel mode of innate immune detection in
      metazoans.

PMID- 22851750
TI  - Modulation of toxin production by the flagellar regulon in Clostridium difficile.
AB  - We show in this study that toxin production in Clostridium difficile is altered
      in cells which can no longer form flagellar filaments. The impact of inactivation
      of fliC, CD0240, fliF, fliG, fliM, and flhB-fliR flagellar genes upon toxin
      levels in culture supernatants was assessed using cell-based cytotoxicity assay,
      proteomics, immunoassay, and immunoblotting approaches. Each of these showed that
      toxin levels in supernatants were significantly increased in a fliC mutant
      compared to that in the C. difficile 630 parent strain. In contrast, the toxin
      levels in supernatants secreted from other flagellar mutants were significantly
      reduced compared with that in the parental C. difficile 630 strain.
      Transcriptional analysis of the pathogenicity locus genes (tcdR, tcdB, tcdE, and
      tcdA) revealed a significant increase of all four genes in the fliC mutant
      strain, while transcription of all four genes was significantly reduced in fliM,
      fliF, fliG, and flhB-fliR mutants. These results demonstrate that toxin
      transcription in C. difficile is modulated by the flagellar regulon. More
      significantly, mutant strains showed a corresponding change in virulence compared
      to the 630 parent strain when tested in a hamster model of C. difficile
      infection. This is the first demonstration of differential flagellum-related
      transcriptional regulation of toxin production in C. difficile and provides
      evidence for elaborate regulatory networks for virulence genes in C. difficile.

PMID- 22851751
TI  - Identification of critical host mitochondrion-associated genes during Ehrlichia
      chaffeensis infections.
AB  - Ehrlichia chaffeensis is an obligate intracellular bacterium that causes human
      monocytic ehrlichiosis (HME). To determine what host components are important for
      bacterial replication, we performed microarray analysis on Drosophila
      melanogaster S2 cells by comparing host gene transcript levels between permissive
      and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven
      genes had increased transcript levels unique to permissive growth conditions 24 h
      postinfection. We screened adult flies that were mutants for several of the
      "permissive" genes for the ability to support Ehrlichia replication. Three
      additional D. melanogaster fly lines with putative mutations in pyrimidine
      metabolism were also tested. Ten fly lines carrying mutations in the genes
      CG6479, separation anxiety, chitinase 11, CG6364 (Uck2), CG6543 (Echs1), withered
      (whd), CG15881 (Ccdc58), CG14806 (Apop1), CG11875 (Nup37), and dumpy (dp) had
      increased resistance to infection with Ehrlichia. Analysis of RNA by quantitative
      real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load
      was decreased in these mutant flies compared to wild-type infected control flies.
      Seven of these genes (san, Cht11, Uck2, Echs1, whd, Ccdc58, and Apop1) encoded
      proteins that had mitochondrial functions or could be associated with proteins
      with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA
      to silence the human UCK2 gene indicates that the disruption of the uridine
      cytidine kinase affects E. chaffeensis replication in human macrophages.
      Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and
      cytosine, suggest that the nucleotide salvage pathway is essential for E.
      chaffeensis replication and that it may be important for the provision of CTP,
      uridine, and cytidine nucleotides.

PMID- 22851752
TI  - Role of a new intimin/invasin-like protein in Yersinia pestis virulence.
AB  - A comprehensive TnphoA mutant library was constructed in Yersinia pestis KIM6 to
      identify surface proteins involved in Y. pestis host cell invasion and bacterial
      virulence. Insertion site analysis of the library repeatedly identified a 9,042
      bp chromosomal gene (YPO3944), intimin/invasin-like protein (Ilp), similar to the
      Gram-negative intimin/invasin family of surface proteins. Deletion mutants of ilp
      were generated in Y. pestis strains KIM5(pCD1(+)) Pgm(-) (pigmentation
      negative)/, KIM6(pCD1(-)) Pgm(+), and CO92. Comparative analyses were done with
      the deletions and the parental wild type for bacterial adhesion to and
      internalization by HEp-2 cells in vitro, infectivity and maintenance in the flea
      vector, and lethality in murine models of systemic and pneumonic plague. Deletion
      of ilp had no effect on bacterial blockage of flea blood feeding or colonization.
      The Y. pestis KIM5 Deltailp strain had reduced adhesion to and internalization by
      HEp-2 cells compared to the parental wild-type strain (P < 0.05). Following
      intravenous challenge with Y. pestis KIM5 Deltailp, mice had a delayed time to
      death and reduced dissemination to the lungs, livers, and kidneys as monitored by
      in vivo imaging using a lux reporter system (in vivo imaging system [IVIS]) and
      bacterial counts. Intranasal challenge in mice with Y. pestis CO92 Deltailp had a
      55-fold increase in the 50% lethal dose ([LD(50)] 1.64 * 10(4) CFU) compared to
      the parental wild-type strain LD(50) (2.98 * 10(2) CFU). These findings
      identified Ilp as a novel virulence factor of Y. pestis.

PMID- 22851753
TI  - Toxoplasma gondii antigens recognized by IgG antibodies differ between mice with
      and without active proliferation of tachyzoites in the brain during the chronic
      stage of infection.
AB  - We examined whether tachyzoite proliferation in the brains of immunocompetent
      hosts during the chronic stage of infection with Toxoplasma gondii induces
      production of IgG antibodies that recognize parasite antigens different from
      those recognized by the antibodies of infected hosts that do not have tachyzoite
      growth. For this purpose, two groups of CBA/J mice, which display continuous
      tachyzoite growth in their brains during the later stage of infection, were
      infected, and one group received treatment with sulfadiazine to prevent
      tachyzoite proliferation during the chronic stage of infection. T. gondii
      antigens recognized by the IgG antibodies from these two groups of mice were
      compared using immunoblotting following separation of tachyzoite antigens by two
      dimensional gel electrophoresis. Several antigens, including the microneme
      protein MIC2, the cyst matrix protein MAG1, and the dense granule proteins GRA4
      and GRA7, were commonly recognized by IgG antibodies from both groups of mice.
      There were multiple antigens recognized mostly by IgG antibodies of only one
      group of mice, either with or without cerebral tachyzoite growth. The antigens
      recognized only by or mostly by the antibodies of mice with cerebral tachyzoite
      growth include MIC6, the rhoptry protein ROP1, GRA2, one heat shock protein
      HSP90, one (putative) HSP70, and the myosin heavy chain. These results indicate
      that levels of IgG antibody to only selected T. gondii antigens increase in
      association with cerebral tachyzoite proliferation (reactivation of infection) in
      immunocompetent hosts with chronic infection.

PMID- 22851754
TI  - Infection with Toxoplasma gondii alters lymphotoxin expression associated with
      changes in splenic architecture.
AB  - B cell responses are required for resistance to Toxoplasma gondii; however, the
      events that lead to production of class-switched antibodies during T. gondii
      infection have not been defined. Indeed, mice challenged with the parasite
      exhibited an expansion of T follicular helper cells and germinal center B cells
      in the spleen. Unexpectedly, this was not associated with germinal center
      formation and was instead accompanied by profound changes in splenic
      organization. This phenomenon was transient and was correlated with a decrease in
      expression of effector proteins that contribute to splenic organization,
      including lymphotoxins alpha and beta. The importance of lymphotoxin was
      confirmed, as the use of a lymphotoxin beta receptor agonist results in partial
      restoration of splenic structure. Splenectomized mice were used to test the
      splenic contribution to the antibody response during T. gondii infection.
      Analysis of splenectomized mice revealed delayed kinetics in the production of
      parasite-specific antibody, but the mice did eventually develop normal levels of
      parasite-specific antibody. Together, these studies provide a better
      understanding of how infection with T. gondii impacts the customized structures
      required for the optimal humoral responses to the parasite and the role of
      lymphotoxin in these events.

PMID- 22851755
TI  - Nocardia brasiliensis cell wall lipids modulate macrophage and dendritic
      responses that favor development of experimental actinomycetoma in BALB/c mice.
AB  - Nocardia brasiliensis is a Gram-positive facultative intracellular bacterium
      frequently isolated from human actinomycetoma. However, the pathogenesis of this
      infection remains unknown. Here, we used a model of bacterial delipidation with
      benzine to investigate the role of N. brasiliensis cell wall-associated lipids in
      experimental actinomycetoma. Delipidation of N. brasiliensis with benzine
      resulted in complete abolition of actinomycetoma without affecting bacterial
      viability. Chemical analyses revealed that trehalose dimycolate and an
      unidentified hydrophobic compound were the principal compounds extracted from N.
      brasiliensis with benzine. By electron microscopy, the extracted lipids were
      found to be located in the outermost membrane layer of the N. brasiliensis cell
      wall. They also appeared to confer acid-fastness. In vitro, the extractable
      lipids from the N. brasiliensis cell wall induced the production of the
      proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and CCL-2 in
      macrophages. The N. brasiliensis cell wall extractable lipids inhibited important
      macrophage microbicidal effects, such as tumor necrosis factor alpha (TNF-alpha)
      and nitric oxide (NO) production, phagocytosis, bacterial killing, and major
      histocompatibility complex class II (MHC-II) expression in response to gamma
      interferon (IFN-gamma). In dendritic cells (DCs), N. brasiliensis cell wall
      associated extractable lipids suppressed MHC-II, CD80, and CD40 expression while
      inducing tumor growth factor beta (TGF-beta) production. Immunization with
      delipidated N. brasiliensis induced partial protection preventing actinomycetoma.
      These findings suggest that N. brasiliensis cell wall-associated lipids are
      important for actinomycetoma development by inducing inflammation and modulating
      the responses of macrophages and DCs to N. brasiliensis.

PMID- 22851756
TI  - Vaccine-induced th17 cells are maintained long-term postvaccination as a distinct
      and phenotypically stable memory subset.
AB  - Th17 cells are increasingly being recognized as an important T helper subset for
      immune-mediated protection, especially against pathogens at mucosal ports of
      entry. In several cases, it would thus be highly relevant to induce Th17 memory
      by vaccination. Th17 cells are reported to exhibit high plasticity and may not
      stably maintain their differentiation program once induced, questioning the
      possibility of inducing durable Th17 memory. Accordingly, there is no consensus
      as to whether Th17 memory can be established unless influenced by continuous Th17
      polarizing conditions. We have previously reported (T. Lindenstrom, et al., J.
      Immunol. 182:8047-8055, 2009) that the cationic liposome adjuvant CAF01 can prime
      both Th1 and Th17 responses and promote robust, long-lived Th1 memory. Here, we
      demonstrate that subunit vaccination in mice with CAF01 leads to establishment of
      bona fide Th17 memory cells. Accordingly, Th17 memory cells exhibited lineage
      stability by retaining both phenotypic and functional properties for nearly 2
      years. Antigen-specific, long-term Th17 memory cells were found to be mobilized
      from lung-draining lymph nodes to the lung following an aerosol challenge by
      Mycobacterium tuberculosis nearly 2 years after their induction and proliferated
      at levels comparable to those of Th1 memory cells. During the infection, the
      vaccine-induced Th17 memory cells expanded in the lungs and adapted Th1
      characteristics, implying that they represent a metastable population which
      exhibits plasticity when exposed to prolonged Th1 polarizing, inflammatory
      conditions such as those found in the M. tuberculosis-infected lung. In the
      absence of overt inflammation, however, stable bona fide Th17 memory can indeed
      be induced by parenteral immunization.

PMID- 22851757
TI  - How does the right gastroepiploic artery compare with the saphenous vein for
      revascularization of the right coronary artery?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was 'is the saphenous vein graft or right gastroepiploic
      artery a better conduit for revascularization of the right coronary artery?' One
      hundred and five articles were found using a designated search, of which 10
      articles were found to represent the best available evidence to answer the
      clinical question. Of these 10 articles, two were reports of a randomized
      controlled trial and represented the highest level of evidence, whereas eight
      articles were retrospective observational studies. All were published between
      2002 and 2012. Outcome measures varied considerably, but mostly included graft
      patency at varying periods of follow-up. The randomized evidence suggested that
      the saphenous vein had better early (6-month) and mid-term (3-year) graft patency
      than the right gastroepiploic artery when used for right coronary artery
      revascularization. The use of the saphenous vein was also found to be predictive
      of superior graft function using multivariate regression; however, a more recent
      propensity score analysis identified gastroepiploic-right coronary grafts to
      yield superior very long-term (>10 years) clinical outcomes. Overall, based on
      the best quality evidence and in view of technical limitations and flow
      characteristics of the right gastroepiploic artery, it appears that saphenous
      vein grafts may offer superior outcomes for revascularization of the right
      coronary artery in most cases, and should be preferentially used.

PMID- 22851758
TI  - Successful extracorporeal membrane oxygenation weaning after cardiac
      resynchronization therapy device implantation in a patient with end-stage heart
      failure.
AB  - We present the case of a 46-year old male with end-stage heart failure due to
      ethyltoxic cardiomyopathy. The patient did not meet the criteria for heart
      transplantation and declined left ventricular assist device implantation. We
      decided to conduct cardiac resynchronization therapy defibrillator (CRT-D)
      implantation. Under general anaesthesia for CRT-D implantation, cardiac function
      worsened. Due to deteriorating haemodynamics, CRT-D implantation was aborted and
      emergent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation
      was performed. Subsequent weaning from ECMO was not possible. We decided to
      proceed with CRT-D implantation while still on ECMO support. With biventricular
      stimulation, cardiac function improved promptly and the patient could be weaned
      from ECMO the same day.

PMID- 22851759
TI  - Role of sepsis in the development of limb muscle weakness in a porcine intensive
      care unit model.
AB  - Severe muscle wasting and loss of muscle function in critically ill mechanically
      ventilated intensive care unit (ICU) patients have significant negative
      consequences on their recovery and rehabilitation that persist long after their
      hospital discharge; moreover, the underlying mechanisms are unclear. Mechanical
      ventilation (MV) and immobilization-induced modifications play an important role
      in these consequences, including endotoxin-induced sepsis. The present study aims
      to investigate how sepsis aggravates ventilator and immobilization-related limb
      muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated
      in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV,
      alone or in combination with sepsis, for 5 days. In previous studies, we have
      shown that ICU intervention alone or in combination with sepsis did not affect
      muscle fiber size on day 5, but a significant decrease was observed in single
      fiber maximal force normalized to cross-sectional area (specific force) when
      sepsis was added to the ICU intervention. According to microarray data, the
      addition of sepsis to the ICU intervention induced a deregulation of > 500 genes,
      such as an increased expression of genes involved in chemokine activity, kinase
      activity, and transcriptional regulation. Genes involved in the regulation of the
      oxidative stress response and cytoskeletal/sarcomeric and heat shock proteins
      were on the other hand downregulated when sepsis was added to the ICU
      intervention. Thus, sepsis has a significant negative effect on muscle function
      in critically ill ICU patients, and chemokine activity and heat shock protein
      genes are forwarded to play an instrumental role in this specific muscle wasting
      condition.

PMID- 22851761
TI  - Dietary n-3 polyunsaturated fatty acid supplementation alters the expression of
      genes involved in the control of fertility in the bovine uterine endometrium.
AB  - The potential for dietary supplementation with n-3 polyunsaturated fatty acids (n
      3 PUFA) to improve reproductive efficiency in cattle has received much interest.
      The mechanisms by which n-3 PUFA may affect physiological and biochemical
      processes in key reproductive tissues are likely to be mediated by significant
      alterations in gene expression. The objective of this study was to examine the
      effects of dietary n-3 PUFA supplementation on global uterine endometrial gene
      expression in cattle. Beef heifers were supplemented with a rumen protected
      source of either a saturated fatty acid (CON; palmitic acid) or high n-3 PUFA (n
      3 PUFA; 275 g) diet per animal per day for 45 days and global gene expression was
      determined in uterine endometrial tissue using an Affymetrix oligonucleotide
      bovine array. A total of 1,807 (946 up- and 861 downregulated) genes were
      differentially expressed following n-3 PUFA supplementation. Dietary n-3 PUFA
      altered numerous cellular processes potentially important in the control of
      reproduction in cattle. These included prostaglandin biosynthesis,
      steroidogenesis and transcriptional regulation, while effects on genes involved
      in maternal immune response and tissue remodeling were also observed. This study
      provides new insights into the effects of n-3 PUFA supplementation on the
      regulation of gene expression in the bovine uterus.

PMID- 22851760
TI  - Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic
      dysfunction in the left ventricle of hypertensive SS/MCWi rats.
AB  - Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce
      fibrosis in rodents after myocardial infarction, resulting in an overall
      improvement in left ventricular function. Little is known about the effectiveness
      of BMMNC therapy in hypertensive heart disease. In the current study, we show
      that delivery of BMMNCs from hypertension protected SS-13(BN)/MCWi donor rats,
      but not BMMNC from hypertension susceptible SS/MCWi donor rats, resulted in 57.2
      and 83.4% reductions in perivascular and interstitial fibrosis, respectively, as
      well as a 60% increase in capillary-to-myocyte count in the left ventricles (LV)
      of hypertensive SS/MCWi recipients. These histological changes were associated
      with improvements in LV compliance and relaxation (103 and 46.4% improvements,
      respectively). Furthermore, improved diastolic function in hypertensive SS/MCWi
      rats receiving SS-13(BN)/MCWi derived BMMNCs was associated with lower clinical
      indicators of heart failure, including reductions in end diastolic pressure (65%)
      and serum brain natriuretic peptide levels (49.9%) with no improvements observed
      in rats receiving SS/MCWi BMMNCs. SS/MCWi rats had a lower percentage of
      endothelial progenitor cells in their bone marrow relative to SS-13(BN)/MCWi
      rats. These results suggest that administration of BMMNCs can prevent or reverse
      pathological remodeling in hypertensive heart disease, which contributes to
      ameliorating diastolic dysfunction and associated symptomology. Furthermore, the
      health and hypertension susceptibility of the BMMNC donor are important factors
      influencing therapeutic efficacy, possibly via differences in the cellular
      composition of bone marrow.

PMID- 22851762
TI  - An engineered monolignol 4-o-methyltransferase depresses lignin biosynthesis and
      confers novel metabolic capability in Arabidopsis.
AB  - Although the practice of protein engineering is industrially fruitful in creating
      biocatalysts and therapeutic proteins, applications of analogous techniques in
      the field of plant metabolic engineering are still in their infancy. Lignins are
      aromatic natural polymers derived from the oxidative polymerization of primarily
      three different hydroxycinnamyl alcohols, the monolignols. Polymerization of
      lignin starts with the oxidation of monolignols, followed by endwise cross
      coupling of (radicals of) a monolignol and the growing oligomer/polymer. The para
      hydroxyl of each monolignol is crucial for radical generation and subsequent
      coupling. Here, we describe the structure-function analysis and catalytic
      improvement of an artificial monolignol 4-O-methyltransferase created by
      iterative saturation mutagenesis and its use in modulating lignin and
      phenylpropanoid biosynthesis. We show that expressing the created enzyme in
      planta, thus etherifying the para-hydroxyls of lignin monomeric precursors,
      denies the derived monolignols any participation in the subsequent coupling
      process, substantially reducing lignification and, ultimately, lignin content.
      Concomitantly, the transgenic plants accumulated de novo synthesized 4-O
      methylated soluble phenolics and wall-bound esters. The lower lignin levels of
      transgenic plants resulted in higher saccharification yields. Our study, through
      a structure-based protein engineering approach, offers a novel strategy for
      modulating phenylpropanoid/lignin biosynthesis to improve cell wall digestibility
      and diversify the repertories of biologically active compounds.

PMID- 22851763
TI  - A light-regulated genetic module was recruited to carpel development in
      Arabidopsis following a structural change to SPATULA.
AB  - A key innovation of flowering plants is the female reproductive organ, the
      carpel. Here, we show that a mechanism that regulates carpel margin development
      in the model flowering plant Arabidopsis thaliana was recruited from light
      regulated processes. This recruitment followed the loss from the basic helix-loop
      helix transcription factor SPATULA (SPT) of a domain previously responsible for
      its negative regulation by phytochrome. We propose that the loss of this domain
      was a prerequisite for the light-independent expression in female reproductive
      tissues of a genetic module that also promotes shade avoidance responses in
      vegetative organs. Striking evidence for this proposition is provided by the
      restoration of wild-type carpel development to spt mutants by low red/far-red
      light ratios, simulating vegetation shade, which we show to occur via phytochrome
      B, PHYTOCHROME INTERACTING FACTOR4 (PIF4), and PIF5. Our data illustrate the
      potential of modular evolutionary events to generate rapid morphological change
      and thereby provide a molecular basis for neo-Darwinian theories that describe
      this nongradualist phenomenon. Furthermore, the effects shown here of light
      quality perception on carpel development lead us to speculate on the potential
      role of light-regulated mechanisms in plant organs that, like the carpel, form
      within the shade of surrounding tissues.

PMID- 22851764
TI  - Structure of androcam supports specialized interactions with myosin VI.
AB  - Androcam replaces calmodulin as a tissue-specific myosin VI light chain on the
      actin cones that mediate D. melanogaster spermatid individualization. We show
      that the androcam structure and its binding to the myosin VI structural (Insert
      2) and regulatory (IQ) light chain sites are distinct from those of calmodulin
      and provide a basis for specialized myosin VI function. The androcam N lobe
      noncanonically binds a single Ca(2+) and is locked in a "closed" conformation,
      causing androcam to contact the Insert 2 site with its C lobe only. Androcam
      replacing calmodulin at Insert 2 will increase myosin VI lever arm flexibility,
      which may favor the compact monomeric form of myosin VI that functions on the
      actin cones by facilitating the collapse of the C-terminal region onto the motor
      domain. The tethered androcam N lobe could stabilize the monomer through contacts
      with C-terminal portions of the motor or recruit other components to the actin
      cones. Androcam binds the IQ site at all calcium levels, constitutively mimicking
      a conformation adopted by calmodulin only at intermediate calcium levels. Thus,
      androcam replacing calmodulin at IQ will abolish a Ca(2+)-regulated, calmodulin
      mediated myosin VI structural change. We propose that the N lobe prevents
      androcam from interfering with other calmodulin-mediated Ca(2+) signaling events.
      We discuss how gene duplication and mutations that selectively stabilize one of
      the many conformations available to calmodulin support the molecular evolution of
      structurally and functionally distinct calmodulin-like proteins.

PMID- 22851765
TI  - Nitrate transport in salivary glands with implications for NO homeostasis.

PMID- 22851766
TI  - Profile of R. Scott Hawley. Interview by Sujata Gupta.

PMID- 22851767
TI  - Olfaction shapes host-parasite interactions in parasitic nematodes.
AB  - Many parasitic nematodes actively seek out hosts in which to complete their
      lifecycles. Olfaction is thought to play an important role in the host-seeking
      process, with parasites following a chemical trail toward host-associated odors.
      However, little is known about the olfactory cues that attract parasitic
      nematodes to hosts or the behavioral responses these cues elicit. Moreover, what
      little is known focuses on easily obtainable laboratory hosts rather than on
      natural or other ecologically relevant hosts. Here we investigate the olfactory
      responses of six diverse species of entomopathogenic nematodes (EPNs) to seven
      ecologically relevant potential invertebrate hosts, including one known natural
      host and other potential hosts collected from the environment. We show that EPNs
      respond differentially to the odor blends emitted by live potential hosts as well
      as to individual host-derived odorants. In addition, we show that EPNs use the
      universal host cue CO(2) as well as host-specific odorants for host location, but
      the relative importance of CO(2) versus host-specific odorants varies for
      different parasite-host combinations and for different host-seeking behaviors. We
      also identified host-derived odorants by gas chromatography-mass spectrometry and
      found that many of these odorants stimulate host-seeking behaviors in a species
      specific manner. Taken together, our results demonstrate that parasitic nematodes
      have evolved specialized olfactory systems that likely contribute to appropriate
      host selection.

PMID- 22851768
TI  - Extrasynaptic site of action for gamma-hydroxybutyrate.

PMID- 22851769
TI  - Pari passu dimers of dimers.

PMID- 22851771
TI  - Glycerophosphocholine (GPC) is a poorly understood biomarker in breast cancer.

PMID- 22851772
TI  - Student debt.

PMID- 22851770
TI  - Control of cyclooxygenase-2 expression and tumorigenesis by endogenous 5
      methoxytryptophan.
AB  - Cyclooxygenase-2 (COX-2) expression is induced by mitogenic and proinflammatory
      factors. Its overexpression plays a causal role in inflammation and
      tumorigenesis. COX-2 expression is tightly regulated, but the mechanisms are
      largely unclear. Here we show the control of COX-2 expression by an endogenous
      tryptophan metabolite, 5-methoxytryptophan (5-MTP). By using comparative
      metabolomic analysis and enzyme-immunoassay, our results reveal that normal
      fibroblasts produce and release 5-MTP into the extracellular milieu whereas A549
      and other cancer cells were defective in 5-MTP production. 5-MTP was synthesized
      from L-tryptophan via tryptophan hydroxylase-1 and hydroxyindole O
      methyltransferase. 5-MTP blocked cancer cell COX-2 overexpression and suppressed
      A549 migration and invasion. Furthermore, i.p. infusion of 5-MTP reduced tumor
      growth and cancer metastasis in a murine xenograft tumor model. We conclude that
      5-MTP synthesis represents a mechanism for endogenous control of COX-2
      overexpression and is a valuable lead for new anti-cancer and anti-inflammatory
      drug development.

PMID- 22851773
TI  - An ethicist's commentary on the sale of a veterinary practice to an associate.

PMID- 22851774
TI  - Potential link between the development of a bleeding syndrome in young calves and
      the consumption of colostrum from cows vaccinated with a killed bovine viral
      diarrhea vaccine.

PMID- 22851775
TI  - Occupational health hazards in veterinary medicine: zoonoses and other biological
      hazards.
AB  - This study describes biological hazards reported by veterinarians working in
      western Canada obtained through a self-administered mailed questionnaire. The
      potential occupational hazards included as biological hazards were zoonotic
      disease events, exposure to rabies, injuries due to bites and scratches, and
      allergies. Only 16.7% (136/812) of responding veterinarians reported the
      occurrence of a zoonosis or exposure to rabies in the past 5 years; the most
      commonly reported event was ringworm. Most bites and scratches (86%) described by
      586 veterinarians involved encounters with cats; 81% of the resulting 163
      infections were due to cat bites or scratches. Approximately 38% of participants
      reported developing an allergy during their career, with 41% of the affected
      individuals altering the way they practiced in response to their allergy.

PMID- 22851776
TI  - Occupational health hazards in veterinary medicine: physical, psychological, and
      chemical hazards.
AB  - This paper reports physical, psychological, and chemical hazards relevant to
      western Canadian veterinarians as obtained by a self-administered mailed
      questionnaire. Nine-three percent (750/806) of veterinarians reported some form
      of injury during the previous 5 years; 17% of respondents (131/791) indicated
      injuries that resulted in 1 or more days off work. Median stress levels were
      similar across work environments; overall, 7% (57/813) indicated either no stress
      or severe stress, while 53% (428/813) indicated moderate stress. Twenty percent
      (3/15) of food animal practitioners and 37% (114/308) of companion animal
      practitioners who took X-rays reported accidental exposure. Accidental exposure
      to gas anesthetic was reported by 69% (394/570) of those in private practice.
      Exposure to chemicals occurred in all work environments. Veterinarians in western
      Canada are at risk of minor to severe injury due to both animal and non-animal
      related causes.

PMID- 22851777
TI  - Use of observed wild bird activity on poultry farms and a literature review to
      target species as high priority for avian influenza testing in 2 regions of
      Canada.
AB  - The risk of avian influenza outbreaks in poultry is partially dependent on the
      probability of contact between domestic poultry and wild birds shedding avian
      influenza (AI) virus. The major objective of this study was to document wild bird
      activity on poultry farms to determine which wild bird species should be targeted
      for AI surveillance in Canada. We collected data in 2 major poultry producing
      regions of Canada, southwestern Ontario and the Fraser Valley of British
      Columbia, on the relative abundance of various wild bird species found on poultry
      farms and on how these species utilized habitat around poultry farms. We reviewed
      the published literature to determine what was known about AI pathobiology in the
      species we observed. From these results we created a list of 10 wild bird species
      that are a priority for further study. These species are the European starling,
      barn swallow, rock dove, American crow, northwestern crow, American robin, dark
      eyed junco, song sparrow, horned lark, and common grackle. Abundance of these and
      other species varied between provinces and seasons.

PMID- 22851778
TI  - Successful treatment of acute respiratory distress syndrome in 2 dogs.
AB  - Acute respiratory distress syndrome (ARDS) was diagnosed in 2 dogs with acute
      dyspnea. Short-term positive pressure ventilation and intense critical and
      nursing care were provided. Both dogs improved and were discharged. Few reports
      describe successful recovery from ARDS. Due to advances in positive pressure
      ventilation and improvement in the supportive care of critically ill veterinary
      patients, the prognosis for ARDS may improve.

PMID- 22851779
TI  - Enteritis associated with Clostridium perfringens type A in 9-month-old calves.
AB  - Four 9-month-old Simmental male calves were presented with a history of sudden
      death. The necropsy and microscopic findings allowed a diagnosis of enteritis and
      severe intraluminal hemorrhage with blood clots in the jejunum, suggestive of
      jejunal hemorrhage syndrome.

PMID- 22851780
TI  - Ectopic thyroid carcinoma infiltrating the right atrium of the heart in a dog.
AB  - A 12-year-old intact female shih tzu dog was diagnosed with an ectopic thyroid
      carcinoma infiltrating the right atrium of the heart. Echocardiography and
      computed tomography were helpful in diagnosis; a definitive diagnosis was made
      based on postmortem histopathology and immunohistochemistry. The patient lived
      428 days beyond diagnosis with only medical management.

PMID- 22851781
TI  - Caudal vena caval thrombosis following treatment of deep digital sepsis.
AB  - A diagnosis of caudal vena caval thrombosis was made by ultrasonography of a
      Holstein cow presented for lethargy and poor milk production. Medical treatment
      was unsuccessful and the cow was euthanized. The diagnosis was confirmed at
      necropsy and Fusobacterium necrophorum was isolated from the thrombus. This paper
      discusses potential novel sources of caval thrombosis in this case.

PMID- 22851782
TI  - Identification of an intra-cranial intra-axial porcupine quill foreign body with
      computed tomography in a canine patient.
AB  - An intra-cranial intra-axial foreign body was diagnosed in a golden retriever dog
      through the use of computed tomography (CT). Confirmed by necropsy, a porcupine
      quill had migrated to the patient's left cerebral hemisphere, likely through the
      oval foramen. This case study demonstrates the efficacy of CT in visualizing a
      quill in the canine brain.

PMID- 22851783
TI  - A novel case of canine disseminated aspergillosis following mating.
AB  - An intact bitch with a history of mating was presented with severe lameness and a
      vulvar discharge. A mixed lytic, proliferative tibial lesion and open pyometra
      were diagnosed. Bone biopsy and uterine culture revealed disseminated
      aspergillosis. This is the first report of Aspergillus pyometra with
      dissemination following mating in the dog.

PMID- 22851784
TI  - Antiemetic efficacy of promethazine on xylazine-induced emesis in cats.
AB  - The prophylactic antiemetic effect of 3 dosages of promethazine injected into
      cats 1 h before administration of xylazine was compared with that of a saline
      solution. Prior treatment with 2 and 4 mg/kg of promethazine significantly
      reduced the frequency of emetic episodes. Promethazine may be used as a
      prophylactic antiemetic in cats treated with xylazine.

PMID- 22851785
TI  - Subclinical fungal endometritis in an 8-year-old Hanoverian mare.
AB  - Clinical and subclinical endometritis are leading causes of reduced reproductive
      efficiency in the mare. Clinical endometritis is relatively easy to diagnose
      during routine physical and ultrasonographic reproductive examinations, whereas
      the diagnosis of subclinical endometritis requires a more detailed work-up. The
      goal of this paper is to review the various options, and describe the regimen
      chosen in a mare with subclinical fungal endometritis.

PMID- 22851786
TI  - The art of veterinary practice: decision-making and quality communication.

PMID- 22851787
TI  - Orthopedic hardware and equipment for the beginner. Part 3: external skeletal
      fixators.

PMID- 22851788
TI  - Statistical Mechanics of Transcription-Factor Binding Site Discovery Using Hidden
      Markov Models.
AB  - Hidden Markov Models (HMMs) are a commonly used tool for inference of
      transcription factor (TF) binding sites from DNA sequence data. We exploit the
      mathematical equivalence between HMMs for TF binding and the "inverse"
      statistical mechanics of hard rods in a one-dimensional disordered potential to
      investigate learning in HMMs. We derive analytic expressions for the Fisher
      information, a commonly employed measure of confidence in learned parameters, in
      the biologically relevant limit where the density of binding sites is low. We
      then use techniques from statistical mechanics to derive a scaling principle
      relating the specificity (binding energy) of a TF to the minimum amount of
      training data necessary to learn it.

PMID- 22851789
TI  - Resistance to change and preference for variable versus fixed response sequences.
AB  - In Experiment 1, 4 pigeons were trained on a multiple chain schedule in which the
      initial link was a variable-interval (VI) 20-s schedule signalled by a red or
      green center key, and terminal links required four responses made to the left (L)
      and/or right (R) keys. In the REPEAT component, signalled by red keylights, only
      LRLR terminal-link response sequences were reinforced, while in the VARY
      component, signalled by green keylights, terminal-link response sequences were
      reinforced if they satisfied a variability criterion. The reinforcer rate for
      both components was equated by adjusting the reinforcer probability for correct
      REPEAT sequences across sessions. Results showed that initial- and terminal-link
      responding in the VARY component was generally more resistant to prefeeding,
      extinction, and response-independent food than responding in the REPEAT
      component. In Experiment 2, the REPEAT and VARY contingencies were arranged as
      terminal links of a concurrent chain and the relative reinforcer rate was
      manipulated across conditions. For all pigeons, initial-link response allocation
      was biased toward the alternative associated with the VARY terminal link. These
      results replicate previous reports that operant variation is more resistant to
      change than operant repetition (Doughty & Lattal, 2001), and show that variation
      is preferred to repetition with reinforcer-related variables controlled.
      Behavioral momentum theory (Nevin & Grace, 2000) predicts the covariation of
      preference and resistance to change in Experiments 1 and 2, but does not explain
      why these aspects of behavior should depend on contingencies that require
      repetition or variation.

PMID- 22851790
TI  - Relative versus absolute stimulus control in the temporal bisection task.
AB  - When subjects learn to associate two sample durations with two comparison keys,
      do they learn to associate the keys with the short and long samples (relational
      hypothesis), or with the specific sample durations (absolute hypothesis)? We
      exposed 16 pigeons to an ABA design in which phases A and B corresponded to tasks
      using samples of 1 s and 4 s, or 4 s and 16 s. Across phases, we varied the
      mapping between the samples and the keys. For group Relative, short and long
      samples were always associated with the same keys (e.g., Phase A: '1s-> Left, 4s
      > Right'; Phase B: '4s-> Left, 16s-> Right'); for group Absolute, the 4-s sample
      was associated always with the same key (e.g., Phase A: '1s-> Left, 4s-> Right';
      Phase B: '16s-> Left, 4s-> Right'). If temporal control is relational, group
      Relative should learn the new task faster than group Absolute, but if temporal
      control is absolute, the opposite should occur. We compared the results with the
      predictions of the Learning-to-Time (LeT) model, which accounts for temporal
      discrimination in terms of absolute stimulus control and stimulus generalization.
      The acquisition curves of the two groups were generally consistent with LeT and
      therefore more consistent with the absolute than the relative hypothesis.

PMID- 22851791
TI  - Saving the best for last? A cross-species analysis of choices between reinforcer
      sequences.
AB  - Two experiments were conducted to compare choices between sequences of
      reinforcers in pigeon (Experiment 1) and human (Experiment 2) subjects, using
      functionally analogous procedures. The subjects made pairwise choices among 3
      sequence types, all of which provided the same overall reinforcerment rate, but
      differed in their temporal patterning. Token reinforcement schedules were used in
      both experiments and the type of exchange schedule varied across blocks of
      sessions. Some conditions permitted immediate exchange of tokens for consumable
      reinforcers (food for pigeons, video access for humans); in other conditions,
      tokens accumulated and were exchanged for consumable reinforcers only at the end
      of the sequence. Choice patterns in the immediate-exchange conditions were
      generally similar across species, with both pigeons and humans preferring
      sequences with the shortest delay to the initial reinforcer in the series. The
      results are broadly consistent with models of temporal discounting expanded to
      include the impact of sequences of delayed reinforcers acting in parallel from
      the time of the choice. Preferences were less consistent with discounting models
      in the delayed exchange conditions. Questionnaire data gathered at the end of the
      experiment were consistent with prior results of questionnaire studies, but
      showed no straightforward relation to the observed choice patterns, urging
      caution in the extrapolation of results from one decision-making domain to the
      other.

PMID- 22851793
TI  - Commitment and self-control in a prisoner's dilemma game.
AB  - Humans often make seemingly irrational choices in situations of conflict between
      a particular smaller-sooner reinforcer and a more abstract, temporally extended,
      but larger reinforcer. In two experiments, the extent to which the availability
      of commitment responses-self-imposed restrictions on future choices-might improve
      self-control in such situations was investigated. Participants played a
      prisoner's dilemma game against a computer that played a tit-for-tat strategy
      cooperating after a participant cooperated, defecting after a participant
      defected. Defecting produced a small-immediate reinforcer (consisting of points
      convertible to gift cards) whereas cooperating increased the amount of subsequent
      reinforcers, yielding a greater overall reinforcer rate. Participants were
      normally free to cooperate or defect on each trial. Additionally, they could
      choose to make a commitment response that forced their choice for the ensuing
      five trials. For some participants, the commitment response forced cooperation;
      for others, it forced defection. Most participants, with either commitment
      response available, chose to commit repeatedly despite a minor point loss for
      doing so. After extended exposure to these contingencies, the commit-to-cooperate
      group cooperated significantly more than a control group (with no commitment
      available). The commit-to-defect group cooperated significantly less than the
      control group. When both commitment alternatives were simultaneously available
      one for cooperation and one for defection-cooperation commitment was strongly
      preferred. In Experiment 2, the commitment alternative was removed at the end of
      the session; gains in cooperation, relative to the control group, were not
      sustained in the absence of the self-imposed behavioral scaffold.

PMID- 22851792
TI  - Individual differences in impulsive choice and timing in rats.
AB  - Individual differences in impulsive choice behavior have been linked to a variety
      of behavioral problems including substance abuse, smoking, gambling, and poor
      financial decision-making. Given the potential importance of individual
      differences in impulsive choice as a predictor of behavioral problems, the
      present study sought to measure the extent of individual differences in a normal
      sample of hooded Lister rats. Three experiments utilized variations of a delay
      discounting task to measure the degree of variation in impulsive choice behavior
      across individual rats. The individual differences accounted for 22-55% of the
      variance in choice behavior across the three experiments. In Experiments 2 and 3,
      the individual differences were still apparent when behavior was measured across
      multiple choice points. Large individual differences in the rate of responding,
      and modest individual differences in timing of responding were also observed
      during occasional peak trials. The individual differences in timing and rate,
      however, did not correlate consistently with individual differences in choice
      behavior. This suggests that a variety of factors may affect choice behavior,
      response rate, and response timing.

PMID- 22851794
TI  - Relative efficacy of human social interaction and food as reinforcers for
      domestic dogs and hand-reared wolves.
AB  - Despite the intimate relationship dogs share with humans in Western society, we
      know relatively little about the variables that produce and maintain dog social
      behavior towards humans. One possibility is that human social interaction is
      itself a reinforcer for dog behavior. As an initial assessment of the variables
      that might maintain dog social behavior, we compared the relative efficacy of
      brief human social interaction to a small piece of food as a reinforcer for an
      arbitrary response (nose touch). We investigated this in three populations of
      canids: shelter dogs, owned dogs, and hand-reared wolves. Across all three canid
      populations, brief social interaction was a relatively ineffective reinforcer
      compared to food for most canids, producing lower responding and longer latencies
      than food.

PMID- 22851795
TI  - Sleep and infectious disease risk.

PMID- 22851796
TI  - ASL imaging of brain function changes during sleep restriction.

PMID- 22851797
TI  - Sleep, circadian rhythms, and critical illness.

PMID- 22851798
TI  - Connecting the dots: from trait vulnerability during total sleep deprivation to
      individual differences in cumulative impairment during sustained sleep
      restriction.

PMID- 22851799
TI  - Aging, subjective sleep quality, and health status: the global picture.

PMID- 22851800
TI  - Update to the AASM Clinical Practice Guideline: "The treatment of restless legs
      syndrome and periodic limb movement disorder in adults-an update for 2012:
      practice parameters with an evidence-based systematic review and meta-analyses".

PMID- 22851802
TI  - Sleep and antibody response to hepatitis B vaccination.
AB  - STUDY OBJECTIVES: Experimental evidence links poor sleep with susceptibility to
      infectious illness; however, it remains to be determined if naturally occurring
      sleep is associated with immune responses known to play a role in protection
      against infection. The aim of this study was to determine whether sleep duration,
      sleep efficiency, and sleep quality, assessed in the natural environment, predict
      magnitude of antibody responses to a novel antigen among community volunteers in
      midlife. DESIGN: Observational. MEASUREMENTS AND RESULTS: Healthy midlife adults
      (n = 125; 70 female; age 40-60 yr) received the standard 3-dose hepatitis B
      vaccination series. Actigraphy and electronic sleep diaries were used to assess
      sleep duration, sleep efficiency, and subjective sleep quality. Viral-specific
      antibody titers were obtained prior to the 2nd and 3rd vaccination to assess
      primary and secondary antibody responses. Clinical protection status (anti
      hepatitis B surface antigen immunoglobulin G >= 10 mIU/ml) was assessed 6 mo
      after the final immunization. Regression analyses revealed that shorter
      actigraphy-based sleep duration was associated with a lower secondary antibody
      response independent of age, sex, body mass index, and response to the initial
      immunization. Shorter sleep duration, measured by actigraphy and sleep diary,
      also predicted a decreased likelihood of being clinically protected from
      hepatitis B at the conclusion of the vaccination series. Neither sleep efficiency
      nor subjective sleep quality were significant predictors of antibody response.
      CONCLUSIONS: Short sleep duration in the natural environment may negatively
      affect in vivo antibody responses to novel antigens, providing a possible
      explanation for observed associations of poor sleep with increased susceptibility
      to infectious disease.

PMID- 22851801
TI  - The treatment of restless legs syndrome and periodic limb movement disorder in
      adults--an update for 2012: practice parameters with an evidence-based systematic
      review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice
      Guideline.
AB  - A systematic literature review and meta-analyses (where appropriate) were
      performed to update the previous AASM practice parameters on the treatments, both
      dopaminergic and other, of RLS and PLMD. A considerable amount of literature has
      been published since these previous reviews were performed, necessitating an
      update of the corresponding practice parameters. Therapies with a STANDARD level
      of recommendation include pramipexole and ropinirole. Therapies with a GUIDELINE
      level of recommendation include levodopa with dopa decarboxylase inhibitor,
      opioids, gabapentin enacarbil, and cabergoline (which has additional caveats for
      use). Therapies with an OPTION level of recommendation include carbamazepine,
      gabapentin, pregabalin, clonidine, and for patients with low ferritin levels,
      iron supplementation. The committee recommends a STANDARD AGAINST the use of
      pergolide because of the risks of heart valve damage. Therapies for RLS secondary
      to ESRD, neuropathy, and superficial venous insufficiency are discussed. Lastly,
      therapies for PLMD are reviewed. However, it should be mentioned that because
      PLMD therapy typically mimics RLS therapy, the primary focus of this review is
      therapy for idiopathic RLS.

PMID- 22851803
TI  - Differential effects of sodium oxybate and baclofen on EEG, sleep,
      neurobehavioral performance, and memory.
AB  - STUDY OBJECTIVES: Sodium oxybate (SO) is a GABAbeta agonist used to treat the
      sleep disorder narcolepsy. SO was shown to increase slow wave sleep (SWS) and EEG
      delta power (0.75-4.5 Hz), both indexes of NREM sleep (NREMS) intensity and
      depth, suggesting that SO enhances recuperative function of NREM. We investigated
      whether SO induces physiological deep sleep. DESIGN: SO was administered before
      an afternoon nap or before the subsequent experimental night in 13 healthy
      volunteers. The effects of SO were compared to baclofen (BAC), another GABAbeta
      receptor agonist, to assess the role of GABAbeta receptors in the SO response.
      MEASUREMENTS AND RESULTS: As expected, a nap significantly decreased sleep need
      and intensity the subsequent night. Both drugs reversed this nap effect on the
      subsequent night by decreasing sleep latency and increasing total sleep time, SWS
      during the first NREMS episode, and EEG delta and theta (0.75-7.25 Hz) power
      during NREMS. The SO-induced increase in EEG delta and theta power was, however,
      not specific to NREMS and was also observed during REM sleep (REMS) and
      wakefulness. Moreover, the high levels of delta power during a nap following SO
      administration did not affect delta power the following night. SO and BAC taken
      before the nap did not improve subsequent psychomotor performance and subjective
      alertness, or memory consolidation. Finally, SO and BAC strongly promoted the
      appearance of sleep onset REM periods. CONCLUSIONS: The SO-induced EEG slow waves
      seem not to be functionally similar to physiological slow waves. Our findings
      also suggest a role for GABAbeta receptors in REMS generation.

PMID- 22851804
TI  - Cerebral perfusion differences between drowsy and nondrowsy individuals after
      acute sleep restriction.
AB  - OBJECTIVES: To investigate changes in resting cerebral blood flow (CBF) after
      acute sleep restriction. To investigate the extent to which changes in CBF after
      sleep restriction are related to drowsiness as manifested in eye-video. DESIGN:
      Participants were scanned for 5 min using arterial spin labeling (ASL) perfusion
      imaging after both sleep-restricted and rested nights. Participants were rated
      for visual signs of drowsiness in the eye-video recorded during the scan.
      SETTING: Lying supine in a 3-Tesla magnetic resonance imaging scanner.
      PARTICIPANTS: Twenty healthy adults (age 20-37 yr) with no history of neurologic,
      psychiatric, or sleep disorder, and with usual time in bed of 7.0-8.5 h.
      INTERVENTIONS: In the night before the sleep-restricted session, participants
      were restricted to 4 h time in bed. RESULTS: There was an overall reduction in
      CBF in the right-lateralized fronto-parietal attentional network after acute
      sleep restriction, although this was largely driven by participants who showed
      strong signs of drowsiness in the eye-video after sleep restriction. Change in
      CBF correlated with change in drowsiness in the basal forebrain-cingulate
      regions. In particular, there was a pronounced increase in CBF in the basal
      forebrain and anterior and posterior cingulate cortex of participants who
      remained alert after sleep restriction. CONCLUSIONS: The pattern of cerebral
      activity after acute sleep restriction is highly dependent on level of
      drowsiness. Nondrowsy individuals are able to increase activity in the arousal
      promoting brain regions and maintain activity in attentional regions. In
      contrast, drowsy individuals are unable to maintain arousal and show decreased
      activity in both arousal-promoting and attentional regions.

PMID- 22851805
TI  - The orexin antagonist SB-649868 promotes and maintains sleep in men with primary
      insomnia.
AB  - STUDY OBJECTIVES: To assess the acute effects of SB-649868 in male subjects with
      Primary Insomnia with regard to (1) objective and subjective sleep parameters,
      (2) safety and tolerability, (3) next-day residual effects. DESIGN: Multicenter,
      randomized, double-blind, placebo-controlled crossover study using a complete set
      of Williams orthogonal Latin Squares SETTING: 9 sleep centers in Germany
      PATIENTS: 52 male subjects with a diagnosis of primary insomnia (difficulty in
      sleep initiation and maintenance) confirmed by polysomnography INTERVENTIONS: SB
      649868 (10, 30, 60 mg) and placebo administered after dinner 90 minutes before
      bedtime MEASUREMENTS AND RESULTS: Sleep effects assessed by polysomnography
      during 2 consecutive nights and by sleep questionnaires completed by subjects
      after each night at the sleep laboratory. Safety and tolerability were assessed
      by adverse events collection, electrocardiogram (ECG), vital signs, laboratory
      tests. Next-day residual effects were assessed by Digit Symbol Substitution Test,
      and modified Verbal Learning Memory Test administered at "lights on" after night
      2. SB-649868 significantly reduced latency to persistent sleep, wake after sleep
      onset (WASO), and increased total sleep time (TST) compared to placebo. A dose
      dependent effect was observed. A dose-dependent increase in absolute and percent
      REM sleep and reduction in REM sleep latency was observed mainly at the 60-mg
      dose. SB-649868 was well tolerated with inconsistent next day residual effects.
      SB-649868 sleep effects were correlated with SB-649868 circulating levels.
      CONCLUSION: The data demonstrate the sleep-promoting properties of the orexin
      antagonist SB-649868 in male patients with insomnia.

PMID- 22851806
TI  - Temporal disorganization of circadian rhythmicity and sleep-wake regulation in
      mechanically ventilated patients receiving continuous intravenous sedation.
AB  - OBJECTIVES: Sleep is regulated by circadian and homeostatic processes and is
      highly organized temporally. Our study was designed to determine whether this
      organization is preserved in patients receiving mechanical ventilation (MV) and
      intravenous sedation. DESIGN: Observational study. SETTING: Academic medical
      intensive care unit. PATIENTS: Critically ill patients receiving MV and
      intravenous sedation. METHODS: Continuous polysomnography (PSG) was initiated an
      average of 2.0 (1.0, 3.0) days after ICU admission and continued >= 36 h or until
      the patient was extubated. Sleep staging and power spectral analysis were
      performed using standard approaches. We also calculated the
      electroencephalography spectral edge frequency 95% SEF95, a parameter that is
      normally higher during wakefulness than during sleep. Circadian rhythmicity was
      assessed in 16 subjects through the measurement of aMT6s in urine samples
      collected hourly for 24-48 hours. Light intensity at the head of the bed was
      measured continuously. MEASUREMENTS AND RESULTS: We analyzed 819.7 h of PSG
      recordings from 21 subjects. REM sleep was identified in only 2/21 subjects. Slow
      wave activity lacked the normal diurnal and ultradian periodicity and homeostatic
      decline found in healthy adults. In nearly all patients, SEF95 was consistently
      low without evidence of diurnal rhythmicity (median 6.3 [5.3, 7.8] Hz, n = 18). A
      circadian rhythm of aMT6s excretion was present in most (13/16, 81.3%) patients,
      but only 4 subjects had normal timing. Comparison of the SEF95 during the
      melatonin-based biological night and day revealed no difference between the 2
      periods (P = 0.64). CONCLUSIONS: The circadian rhythms and PSG of patients
      receiving mechanical ventilation and intravenous sedation exhibit pronounced
      temporal disorganization. The finding that most subjects exhibited preserved, but
      phase delayed, excretion of aMT6s suggests that the circadian pacemaker of such
      patients may be free-running.

PMID- 22851807
TI  - Effects of age, gender, and retirement on perceived sleep problems: results from
      the VISAT combined longitudinal and cross-sectional study.
AB  - OBJECTIVES: This study examined the effects of age, gender, and retirement on the
      subjective frequency of various sleep problems in individuals on a normal work
      schedule. DESIGN: Data were taken from the VISAT study (Aging, Health, - Work),
      which allowed both cross-sectional and longitudinal aspects of age-related
      changes to be examined. SETTING: Various sorts of companies in southern France.
      PARTICIPANTS: The cohorts comprised 623 male and female, employed and retired,
      wage earners who were 32, 42, 52, and 62 years old at the time of the first
      measurement (t1, 1996), and who were seen again 5 (t2) and 10 (t3) years later.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Subjective ratings of the frequency
      of sleep problems and hypnotic usage were recorded on all 3 occasions, as was the
      employment status of the individuals. After controlling for age and gender, an
      effect of decade was observed for difficulty falling asleep and difficulty
      maintaining sleep, indicating that the frequency of these sleep problems was
      rated higher in 2006 than in 1996 by people of the same age at both measurement
      occasions. The perceived frequency of difficulty maintaining sleep, difficulty
      getting back to sleep, and premature awakening was found to increase up to the
      mid-50s but to then remain relatively constant, or even in the case of premature
      awakening to reduce, up to the age of 72. There was also a significant
      improvement in premature awakening among those individuals who changed from being
      active to being retired during the study period (n = 111). In contrast, the rated
      frequency of difficulty falling asleep and hypnotic usage increased fairly
      linearly over the entire age range. CONCLUSIONS: Sleep complaints were reported
      early in the workers' lives, and were more frequent with age, but some of them
      improved after retirement, especially the complaint of premature awakening.

PMID- 22851808
TI  - Accommodating adolescent sleep-wake patterns: the effects of shifting the timing
      of sleep on training effectiveness.
AB  - STUDY OBJECTIVE: This study evaluated the effect of accommodating adolescent
      sleep-wake patterns by altering the timing of the major sleep period of US Army
      recruits. DESIGN: The quasi-experimental study compared recruits assigned to one
      of two training companies: one with a customary sleep regimen (20:30 to 04:30)
      while the other employed a phase-delayed sleep regimen (23:00 to 07:00), the
      latter aligning better with biologically driven sleep-wake patterns of
      adolescents. SETTING: The study was conducted during Basic Combat Training (BCT)
      at Fort Leonard Wood, Missouri. TRAINEES: The study included 392 trainees: 209
      received the intervention, while 183 composed the Comparison group. MEASUREMENTS
      AND RESULTS: Demographic and psychophysiological measures were collected on all
      trainees. Weekly assessments of subjective fatigue and mood, periodic physical
      fitness, marksmanship scores, and attrition rates from BCT were studied.
      Actigraphy was collected on approximately 24% of trainees. Based on actigraphy,
      trainees on the phase-delayed sleep schedule obtained 31 m more sleep/night than
      trainees on the customary sleep schedule. The Intervention group reported less
      total mood disturbance relative to baseline. Improvements in marksmanship
      correlated positively with average nightly sleep during the preceding week when
      basic marksmanship skills were taught. No differences were seen in physical
      fitness or attrition rates. In contrast to the Intervention group, the Comparison
      group was 2.3 times more likely to experience occupationally significant fatigue
      and 5.5 times more likely to report poor sleep quality. CONCLUSIONS:
      Accommodating adolescent sleep patterns significantly improves mental health and
      performance in the training environment.

PMID- 22851809
TI  - Deterioration of neurobehavioral performance in resident physicians during
      repeated exposure to extended duration work shifts.
AB  - STUDY OBJECTIVES: Although acute sleep loss during 24- to 30-h extended duration
      work shifts (EDWS) has been shown to impair the performance of resident
      physicians, little is known about the effects of cumulative sleep deficiency on
      performance during residency training. Chronic sleep restriction induces a
      gradual degradation of neurobehavioral performance and exacerbates the effects of
      acute sleep loss in the laboratory, yet the extent to which this occurs under
      real-world conditions is unknown. In this study, the authors quantify the time
      course of neurobehavioral deterioration due to repeated exposure to EDWS during a
      3-week residency rotation. DESIGN: A prospective, repeated-measures, within
      subject design. SETTING: Medical and cardiac intensive care units, Brigham and
      Women's Hospital, Boston, MA. PARTICIPANTS: Thirty-four postgraduate year one
      resident physicians (23 males; age 28.0 +/- 1.83 (standard deviation) years)
      MEASUREMENTS AND RESULTS: Residents working a 3-week Q3 schedule (24- to 30-h
      work shift starts every 3(rd) day), consisting of alternating 24- to 30-h (EDWS)
      and approximately 8-h shifts, underwent psychomotor vigilance testing before,
      during, and after each work shift. Mean response time, number of lapses, and
      slowest 10% of responses were calculated for each test. Residents also maintained
      daily sleep/wake/work logs. EDWS resulted in cumulative sleep deficiency over the
      21-day rotation (6.3 h sleep obtained per day; average 2.3 h sleep obtained per
      extended shift). Response times deteriorated over a single 24- to 30-h shift (P <
      0.0005), and also cumulatively with each successive EDWS: Performance on the
      fifth and sixth shift was significantly worse than on the first shift (P < 0.01).
      Controlling for time of day, there was a significant acute (time on shift) and
      chronic (successive EDWS) interaction on psychomotor vigilance testing response
      times (P < 0.05). CONCLUSIONS: Chronic sleep deficiency caused progressive
      degradation in residents' neurobehavioral performance and exacerbated the effects
      of acute sleep loss inherent in the 24- to 30-h EDWS that are commonly used in
      resident schedules.

PMID- 22851810
TI  - Snoring and severity of symptomatic and asymptomatic carotid stenosis: a
      population-based study.
AB  - BACKGROUND: Obstructive sleep apnea has increasingly been linked to
      cardiovascular damage. More recently, the snoring component itself has been
      independently linked to the presence of carotid atheroma, via local arterial
      trauma. We aimed to identify whether a snoring history is a risk factor for
      carotid stenosis in individuals presenting with a TIA or ischemic stroke.
      METHODS: Participants in the Oxford Vascular Study (OXVASC) were asked about
      their snoring history as part of an entry questionnaire. In 561 individuals with
      a recent TIA or stroke, who had both a complete snoring questionnaire and carotid
      imaging, the relationship between presence and severity of snoring and the degree
      of carotid artery stenosis in both the symptomatic (culprit) and asymptomatic
      (non-culprit) sides. RESULTS: Of 561 participants (287 male, mean/SD age =
      73.3/11.0 years), 90 (16.0%) had >= 50% carotid stenosis, and 154 (27.5%) snored
      frequently (>= 1-2 times/week). No significant associations were identified
      between frequency of self-reported snoring, and the degree of culprit and non
      culprit carotid vessel stenosis, or plaque morphology. CONCLUSIONS: No
      significant association could be identified between a history of frequent snoring
      and the presence of carotid atheroma, degree of stenosis, or plaque type.

PMID- 22851811
TI  - Residual sleep disturbances in patients remitted from major depressive disorder:
      a 4-year naturalistic follow-up study.
AB  - STUDY OBJECTIVES: To investigate the prevalence and clinical, psychosocial, and
      functional correlates of residual sleep disturbances in remitted depressed
      outpatients. DESIGN: A 4-yr prospective observational study in a cohort of
      psychiatric outpatients with major depressive disorder was conducted with a
      standardized diagnostic psychiatric interview and a packet of questionnaires,
      including a sleep questionnaire, Hospital Anxiety and Depression Scale, NEO
      personality inventory, and Short Form-12 Health Survey. SETTINGS: A university
      affiliated psychiatric outpatient clinic. INTERVENTIONS: N/A MEASUREMENTS AND
      RESULTS: Four hundred twenty-one depressed outpatients were recruited at
      baseline, and 371 patients (mean age 44.6 +/- 10.4 yr, female 81.8%; response
      rate 88.1%) completed the reassessments, in which 41% were classified as remitted
      cases. One year prevalence of frequent insomnia at baseline and follow-up in
      remitted patients was 38.0% and 19.3%, respectively. One year prevalence of
      frequent nightmares at baseline and follow-up was 24.0% and 9.3%, respectively.
      Remitted patients with residual insomnia were more likely to be divorced (P <
      0.05) and scored higher on the anxiety subscale (P < 0.05). Remitted patients
      with residual nightmares were younger (P < 0.05) and scored higher on neuroticism
      (P < 0.05) and anxiety subscales (P < 0.01). Residual insomnia and nightmares
      were associated with various aspects of impaired quality of life. Residual
      nightmares was associated with suicidal ideation (odds ratio = 8.40; 95%
      confidence interval 1.79-39.33). CONCLUSIONS: Residual sleep disturbances,
      including insomnia and nightmares, were commonly reported in remitted depressed
      patients with impaired quality of life and suicidal ideation. A constellation of
      psychosocial and personality factors, baseline sleep disturbances, and comorbid
      anxiety symptoms may account for the residual sleep disturbances. Routine
      assessment and management of sleep symptoms are indicated in the integrated
      management of depression.

PMID- 22851812
TI  - Trait-like vulnerability to total and partial sleep loss.
AB  - OBJECTIVE: To determine the extent to which individual differences in
      vulnerability to total sleep deprivation also reflect individual differences in
      vulnerability to multiple nights of sleep restriction. DESIGN: Two sleep loss
      conditions (order counterbalanced) separated by 2 to 4 weeks: (a) total sleep
      deprivation (TSD) of 2 nights (63 h continuous wakefulness); (b) sleep
      restriction (SR) of 7 nights of 3 h nightly time in bed (TIB). Both conditions
      were preceded by 7 in-laboratory nights with 10 h nightly TIB; and followed by 3
      recovery nights with 8 h nightly TIB. Measures of cognitive performance
      (psychomotor vigilance, working memory [1-Back], and mathematical processing),
      objective alertness, subjective sleepiness, and mood were obtained at regular
      intervals under both conditions. Intra-class correlation coefficients (ICC) were
      computed using outcome metrics averaged over the last day (08:00-20:00) of TSD
      and SR. SETTING: Residential sleep/performance testing facility. PARTICIPANTS:
      Nineteen healthy adults (ages 18-39; 11 males, 8 females). INTERVENTIONS: 2
      nights of TSD and 7 nights SR (3 h nightly TIB). RESULTS: volunteers who
      displayed greater vulnerability to TSD displayed greater vulnerability to SR on
      cognitive performance tasks (ICC: PVT lapses = 0.89; PVT speed = 0.86; 1-Back =
      0.88; mathematical processing = 0.68, Ps < 0.05). In addition, trait-like
      responsivity to TSD/SR was found for mood variables vigor (ICC = 0.91), fatigue
      (ICC = 0.73), and happiness (ICC = 0.85) (all Ps < 0.05). CONCLUSION: Resilience
      to sleep loss is a trait-like characteristic that reflects an individual's
      ability to maintain performance during both types of sleep loss (SR and TSD).
      Whether the findings extend to sleep schedules other than those investigated here
      (63 h of TSD and 7 nights of 3 h nightly TIB) will be the focus of future
      studies.

PMID- 22851813
TI  - Sleep problems: an emerging global epidemic? Findings from the INDEPTH WHO-SAGE
      study among more than 40,000 older adults from 8 countries across Africa and
      Asia.
AB  - OBJECTIVE: To estimate the prevalence of sleep problems and the effect of
      potential correlates in low-income settings from Africa and Asia, where the
      evidence is lacking. DESIGN: Cross-sectional. SETTING: Community-wide samples
      from 8 countries across Africa and Asia participating in the INDEPTH WHO-SAGE
      multicenter collaboration during 2006-2007. The participating sites included
      rural populations in Ghana, Tanzania, South Africa, India, Bangladesh, Vietnam,
      and Indonesia, and an urban area in Kenya. PARTICIPANTS: There were 24,434 women
      and 19,501 men age 50 yr and older. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
      Two measures of sleep quality, over the past 30 days, were assessed alongside a
      number of sociodemographic variables, measures of quality of life, and
      comorbidities. Overall, 16.6% of participants reported severe/extreme nocturnal
      sleep problems, with a striking variation across the 8 populations, ranging from
      3.9% (Purworejo, Indonesia and Nairobi, Kenya) to more than 40.0% (Matlab,
      Bangladesh). There was a consistent pattern of higher prevalence of sleep
      problems in women and older age groups. In bivariate analyses, lower education,
      not living in partnership, and poorer self-rated quality of life were
      consistently associated with higher prevalence of sleep problems (P < 0.001). In
      multivariate logistic regression analyses, limited physical functionality or
      greater disability and feelings of depression and anxiety were consistently
      strong, independent correlates of sleep problems, in both women and men, across
      the 8 sites (P < 0.001). CONCLUSIONS: A large number of older adults in low
      income settings are currently experiencing sleep problems, which emphasizes the
      global dimension of this emerging public health issue. This study corroborates
      the multifaceted nature of sleep problems, which are strongly linked to poorer
      general well-being and quality of life, and psychiatric comorbidities.

PMID- 22851817
TI  - Use of mesh in vaginal pelvic organ prolapse surgery: prolapse surgery-an
      overview.

PMID- 22851816
TI  - PGI2 as a regulator of inflammatory diseases.
AB  - Prostacyclin, or PGI(2), is an end product derived from the sequential metabolism
      of arachidonic acid via cyclooxygenase and PGI synthase (PGIS). The receptor for
      PGI(2), IP, can be found on a variety of cell types and signaling through this
      receptor exhibits broad physiological effects. Historically, PGI(2) has been
      understood to play a role in cardiovascular health, specifically having powerful
      vasodilatory effects via relaxation of smooth muscle and inhibiting of platelet
      aggregation. For these reasons, PGI(2) has a long history of use for the
      treatment of pulmonary arterial hypertension (PAH). Only recently, its importance
      as an immunomodulatory agent has been investigated. PGI(2) regulates both the
      innate and adaptive immune systems and its effects are, for the most part,
      thought to be anti-inflammatory or immunosuppressive in nature, which may have
      implications for its further clinical use.

PMID- 22851818
TI  - Influenza A H1N1 2009 (Swine Flu) and Pregnancy.
AB  - The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August
      2010. Although the pandemic is now over, the virus has emerged as the predominant
      strain in the current seasonal influenza phase in the northern hemisphere. The A
      H1N1 influenza is a novel strain of the influenza A virus and is widely known as
      swine flu. The virus contains a mixture of genetic material from human, pig and
      bird flu virus. It is a new variety of flu which people have not had much
      immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages
      about vaccination and treatment seem to be taken slowly by the clinical
      profession. Most people affected by the virus, including pregnant women, suffer a
      mild viral illness, and make a full recovery. The median duration of illness is
      around seven days. This influenza typically affects the younger age group i.e.
      from the ages of 5-65 years. Current experience shows that the age group
      experiencing increased morbidity and mortality rates are in those under 65 years
      of age. Pregnant women, because of their altered immunity and physiological
      adaptations, are at higher risk of developing pulmonary complications, especially
      in the second and third trimesters. In the United Kingdom, twelve maternal deaths
      were reported to be associated with the H1N1 virus during the pandemic and clear
      avoidable factors were identified (Modder, Review of Maternal Deaths in the UK
      related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy
      outcomes were also poor for women who were affected by the virus with a fivefold
      increase in the perinatal mortality rate and threefold increase in the preterm
      delivery rate (Yates et al. Health Technol Assess 14(34):109-182, 2010). There
      continues to be a low uptake of the flu vaccine and commencement of antiviral
      treatment for pregnant women.

PMID- 22851819
TI  - Prevention of Parent to Child Transmission of HIV (PPTCT): An Effort of 4 Years
      in a Tertiary Centre.
AB  - OBJECTIVE: The aim of this study was to see the fetomaternal outcome of pregnancy
      in HIV positive mother. METHODS: This study was conducted in the department of
      OBGYN Medical College Kolkata from 1st January 2004 to 31st December 2007, a
      period of 4 years since the establishment of PPTCT centre in our institution. All
      the pregnant women attending the antenatal clinic for consultation and those
      coming directly to labour room for delivery (unbooked cases) were counseled for
      HIV testing, informed consent was obtained and blood samples collected for HIV
      testing. Babies of HIV positive women delivered were followed up to 18 months for
      testing. RESULTS: The no. of women detected positive were 28, 53, 69 and 98
      (total 248) in the consecutive years. Therefore the seroprevalence of HIV was
      0.41, 0.63, 0.67 and 0.76% in 2004, 2005, 2006 and 2007 respectively. Out of 248
      women who were detected positive in the 3 years, only 103 (41.53%) delivered in
      our institution. 32 (12.90%) underwent MTP. But unfortunately 113 (i.e. 248 -
      (103 + 32) = 113) were lost to follow up during antenatal care. Out of the 95
      live births, only 46 babies have been tested so far out of which only one is
      reactive, 45 are non reactive. CONCLUSION: The main obstacle we faced was in
      following up the mother and the baby. To achieve a high success rate, PPTCT
      programmes must have well-trained, supportive staff who take great care to ensure
      confidentiality. They must be backed up by effective HIV testing and counseling
      programmes and by good quality HIV/AIDS education, which is essential to
      eliminate myths and misunderstandings among pregnant women, and to counter stigma
      and discrimination in the wider community.

PMID- 22851815
TI  - Optimizing dendritic cell-based immunotherapy: tackling the complexity of
      different arms of the immune system.
AB  - Earlier investigations have revealed a surprising complexity and variety in the
      range of interaction between cells of the innate and adaptive immune system. Our
      understanding of the specialized roles of dendritic cell (DC) subsets in innate
      and adaptive immune responses has been significantly advanced over the years.
      Because of their immunoregulatory capacities and because very small numbers of
      activated DC are highly efficient at generating immune responses against
      antigens, DCs have been vigorously used in clinical trials in order to elicit or
      amplify immune responses against cancer and chronic infectious diseases. A better
      insight in DC immunobiology and function has stimulated many new ideas regarding
      the potential ways forward to improve DC therapy in a more fundamental way. Here,
      we discuss the continuous search for optimal in vitro conditions in order to
      generate clinical-grade DC with a potent immunogenic potential. For this, we
      explore the molecular and cellular mechanisms underlying adequate immune
      responses and focus on most favourable DC culture regimens and activation stimuli
      in humans. We envisage that by combining each of the features outlined in the
      current paper into a unified strategy, DC-based vaccines may advance to a higher
      level of effectiveness.

PMID- 22851820
TI  - Estimation of lipid profile in subjects of preeclampsia.
AB  - OBJECTIVES: To evaluate lipid profiles in subjects with preeclampsia. To
      determine if there is any change in lipid profiles in subject of preeclampsia as
      compared to normal antenatal females, non-pregnant females and post partum
      females. METHODS: Study was carried out on pregnant women and non pregnant women
      attending or admitted in the Obstetrics and Gynecology Department of SSG
      Hospital, Baroda between 1st June 2007 to 31st May 2008. Each serum sample from
      different groups was evaluated for Total cholesterol(mg/dl), Triglyceride
      (mg/dl), HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl) and VLDL-cholesterol
      (mg/dl) using diagnostic kits and a comparison drawn and analyzed using t-test
      and chi-square test. RESULTS: Dyslipidemia in the form of significantly decreased
      HDL concentration and significantly increased total cholesterol, LDL, VLDL &
      Triglycerides concentration is conspicuously evident in subjects of preeclampsia
      as compared to non pregnant, normotensive pregnant and postpartum subjects.
      CONCLUSION: Dyslipidemia is significantly evident in preeclampsia and plays an
      important pathological role. The various causative factors for dyslipidemia and
      its prevention need to be further studied and evaluated.

PMID- 22851821
TI  - Low Dose Epidural Analgesia During Labor: Comparison Between Patient Controlled
      Epidural Analgesia with Basal Continuous Infusion and Intermittent Bolus
      Technique.
AB  - OBJECTIVES: To compare the efficacy and safety of patient controlled epidural
      analgesia with basal continuous infusion versus intermittent bolus for labor
      analgesia using fentanyl and bupivacaine. METHODS: In this prospective study, 60
      parturients having singleton term uncomplicated pregnancy in early active labor
      were included. 30 parturients were allocated to receive patient controlled
      epidural analgesia + basal continuous infusion (Group-A) and 30 received
      intermittent bolus on demand (Group-B). Efficacy of technique was assessed in
      terms of quality of analgesia on 0-10 cm verbal analogue scale. Effect on labor
      was assessed by duration of labor, mode of delivery, and parturient's
      satisfaction. Neonatal outcome was measured by Apgar score. Data were expressed
      as mean +/- SD and analysed using Student 't' test and chi square test where
      appropriate. P < 0.05 was considered statistically significant. RESULTS:
      Analgesic efficacy of both the groups was comparable. Maternal satisfaction was
      better in group A than in group B but the results did not achieve statistical
      significance. Effect on labor and neonatal outcome were comparable. CONCLUSIONS:
      Both the techniques appear to be safe for the mother and neonate with excellent
      analgesic efficacy. In a busy obstetric unit with increased demand of epidural
      analgesia, patient controlled epidural analgesia with basal continuous infusion
      may be preferred.

PMID- 22851822
TI  - A Study to Compare the Efficacy of Misoprostol, Oxytocin, Methyl-ergometrine and
      Ergometrine-Oxytocin in Reducing Blood Loss in Active Management of 3rd Stage of
      Labor.
AB  - OBJECTIVES: The purpose of the study was to compare the efficacy of misoprostol
      400 MUg per rectally, injection oxytocin 10 IU intramuscular, injection
      methylergometrine 0.2 mg intravenously and injection (0.5 mg ergometrine + 5 IU
      oxytocin) intramuscular on reducing blood loss in third stage of labor, duration
      of third stage of labor, effect on haemoglobin of the patient, need of additional
      oxytocics or blood transfusion and associated side effects and complications.
      STUDY DESIGN: A prospective non-randomized uncontrolled study was carried out in
      the Department of Obstetrics and Gynecology, SSG Hospital and Medical College,
      Baroda enrolling 200 women and dividing them into four groups. Active management
      of 3rd stage of labor was done using one of the 4 uterotonics as per the group of
      the patient. The main outcome measures were the amount of blood loss, the
      incidence of postpartum hemorrhage and a drop in hemoglobin concentration from
      before delivery to 24 h after delivery. RESULTS: Methylergometrine was found to
      be superior to rest of the drugs in the study with lowest duration of third stage
      of labor (P = 0.000096), lowest amount of blood loss (P = 0.000017) and lowest
      incidence of PPH (P = 0.03). There was no significant difference in the pre
      delivery and the post-delivery hemoglobin concentration amongst the four groups
      with P = 0.061. The need of additional oxytocics and blood transfusion was
      highest with misoprostol as compared to all other drugs used in the study with P
      = 0.037 and 0.009, respectively. As regards side effects, misoprostol was
      associated with shivering and pyrexia in significantly high number of patients as
      compared to the other drugs used in the study while nausea, vomiting and headache
      were more associated with methylergometrine and ergometrine-oxytocin. However all
      the side effects were acceptable and preferable to the excessive blood loss.
      CONCLUSION: Methylergometrine has the best uterotonic drug profile amongst the
      drugs used, strongly favouring its routine use as oxytocic for active management
      of third stage of labor. Misoprostol was found to cause a higher blood loss
      compared to other drugs and hence should be used only in low resource setting
      where other drugs are not available. The role of misoprostol in third stage of
      labor needs larger studies to be proved.

PMID- 22851823
TI  - Circadian pattern of blood pressure in normal pregnancy and preeclampsia.
AB  - AIMS #ENTITYSTARTX00026; OBJECTIVE: To find out the circadian pattern of blood
      pressure in normotensive pregnant women and in women with preeclampsia. METHOD: A
      cross-sectional prospective observational case control study. Blood pressure was
      sampled in thirty-five normotensive pregnant women (control) and thirty five
      preeclamptic women (study group) by using non-invasive automatic ambulatory blood
      pressure monitoring machine for 72 h. RESULTS: Blood pressure (BP) was not
      constant over 24 h period and it oscillated from time to time in control group.
      BP was maximum during early part of afternoon. However, in preeclampsia besides
      quantitative increase in BP, circadian BP oscillations were less pronounced and
      in around 50% subjects BP was maximum during evening and night hours. CONCLUSION:
      Both systolic and diastolic BP showed definite reproducible circadian pattern in
      both preeclamptic and normotensive pregnant women. This pattern both
      quantitatively and qualitatively was different in preeclamptic women.
      Standardized 24 h BP monitoring allows quantitative and qualitative evaluation of
      hypertensive status and is important for timing and dosing of antihypertensive
      medications.

PMID- 22851824
TI  - Comparative Study of Intra-cervical Foley's Catheter and PGE(2) Gel for Pre
      induction Ripening (Cervical).
AB  - AIM: The success of induction of labor depends on the cervical status at the time
      of induction. OBJECTIVE: For effective cervical ripening both Foley's catheter
      and PGE(2) gel are used. The aim of this study was to compare the efficacy of
      intra cervical Foley's catheter and intra cervical PGE(2) gel in cervical
      ripening for the successful induction of labor. STUDY DESIGN: A randomized,
      prospective study was conducted in the Dept of OBGY, GMCH, Aurangabad from July
      2005-January 2008. 400 patients at term with a Bishop's score <=3 with various
      indications for induction were randomly allocated to receive (200 pts) intra
      cervical Foley's catheter or PGE(2) gel (200 pts). After 6 h post induction,
      Bishop's score was noted labor was augmented if required. Statistical analysis
      was done using Chi square test and t test. RESULT: The groups were comparable
      with respect to maternal age, gestation age, indication of induction and initial
      Bishop's score. Both the groups showed significant change in the Bishop's score,
      5.56 +/- 1.89 and 5.49 +/- 1.82 for Foley's catheter and PGE(2) gel,
      respectively, P < 0.001; However there was no significant difference between the
      two groups. There was no significant difference in the side effects. Twenty eight
      cesarean sections (14%) were performed in Group A and 37 (18.5%) were performed
      in Group B (not significant). The induction to delivery interval was 15.32 +/-
      5.24 h in Group A and 14.2 +/- 5.14 h in Group B (P = 0.291). Apgar scores, birth
      weights and NICU admissions showed no difference between the two groups.
      CONCLUSION: This study shows that both Foley's Catheter and PGE(2) gel are
      equally effective in pre induction cervical ripening.

PMID- 22851825
TI  - Implanon: subdermal single rod contraceptive implant.
AB  - OBJECTIVES: Study was conducted to determine acceptability, efficacy, safety,
      return of fertility with Implanon. METHODS: Volunteers having regular
      menstruation, requiring spacing formed study population. Implanon was inserted
      within 5 days of LMP or concurrent with MTP. Woman was asked to record bleeding
      pattern, side effects. Implanon duration was 3 years but Implanon was removed
      before, if patient wanted pregnancy/for side effects. Subjects who did not adopt
      family planning method after removal were followed up for return of ovulation and
      pregnancy. RESULTS: 200 subjects were enrolled (160 within 5 days of LMP, 40
      concurrent with MTP). 74 implanon removals were done. (16 after tenure
      completion, 58 for other reasons.) 16% cases discontinued implanon for
      polymenorrhagia, 10% for irregular bleeding, 4.5% for amenorrhea. There was no
      failure of implanon. 40% had return of ovulation within one month, 95.8%
      conceived within 12 months. CONCLUSIONS: Implanon is safe, effective, well
      accepted method of contraception.

PMID- 22851826
TI  - Study of endometrial pathology in abnormal uterine bleeding.
AB  - INTRODUCTION: Abnormal uterine bleeding (AUB) is the commonest presenting symptom
      in gynaecology out-patient department. Endometrial sampling could be effectively
      used as the first diagnostic step in AUB, although at times, its interpretation
      could be quite challenging to the practicing pathologists. This study was done to
      evaluate histopathology of endometrium for identifying the endometrial causes of
      AUB. We also tried to observe the incidence of various pathology in different age
      groups presenting with abnormal uterine bleeding. MATERIAL AND METHODS: This was
      a study done at Sri Ramachandra Medical College and Research Institute, Chennai,
      India on 620 patients who presented with AUB from June 2005-June 2006. Out of
      which 409 cases of isolated endometrial lesions diagnosed on histopathology were
      selected for the final analyses. A statistical analysis between age of
      presentation and specific endometrial causes was done using chi(2) test. RESULTS:
      The most common age group presenting with AUB was 41-50 years (33.5%). The
      commonest pattern in these patients was normal cycling endometrium (28.4%). The
      commonest pathology irrespective of the age group was disordered proliferative
      pattern (20.5%). Other causes identified were complications of pregnancy (22.7%),
      benign endometrial polyp (11.2%), endometrial hyperplasias (6.1%), carcinomas
      (4.4%) and chronic endometritis (4.2%). Endometrial causes of AUB and age pattern
      was statistically significant with P value <0.05. CONCLUSION: There is an age
      specific association of endometrial lesions. In perimenopausal women AUB is most
      commonly dysfunctional in origin and in reproductive age group, one should first
      rule out complications of pregnancy. The incidence of disordered proliferative
      pattern was significantly high in this study, suggesting an early presentation of
      these patients.

PMID- 22851827
TI  - LEEP Verses Cryotherapy in CIN.
AB  - OBJECTIVE: To compare the effectiveness and safety profile of LEEP (Loop
      Electrosurgical Excision Procedure) verses cryotherapy in the treatment of CIN.
      MATERIAL AND METHOD: Women with abnormal pap smears were subjected to VIA and
      VILLI followed by colposcopy. A total of 200 cases were included in this
      prospective study. Once the diagnosis of CIN was confirmed on histopathology, the
      women were subjected to either cryotherapy or LEEP randomly. They were follow up
      at 1, 6 and 12 months. At 12 months follow up, cervix was subjected to VIA, VILLI
      and colposcopy. Chi square test was used to analyze the data. OBSERVATIONS: The
      efficacy of cryotherapy was found to be 88% and that of LEEP was 94% which is not
      significantly different. The overall cure rate of symptoms was 82 and 79% in
      cryosurgery and LEEP group, respectively. CONCLUSION: Although LEEP was
      associated with higher cure rates but the difference is not significant
      statistically. Either method if used appropriately gives good results in
      treatment of CIN lesions, however, LEEP seems to have an edge over cryotherapy
      when used on severe lesions.

PMID- 22851828
TI  - Complementary procedures in cervical cancer screening in low resource settings.
AB  - OBJECTIVE: To evaluate the efficacy of pap smear, HPV DNA testing and colposcopy
      and to determine the approach for cervical cancer screening in low resource
      settings. METHODS: Eight hundred non pregnant married women above 30 years of age
      were studied and subjected to pap smear examination. Hysterectomised women were
      excluded from the study. Selected patients were followed by HPV DNA testing by
      Hybrid Capture II method, colposcopy and biopsy. Sensitivity, specificity,
      Positive predictive value (PPV), Negative predictive value (NPV), diagnostic
      accuracy and kappa value (k) were calculated for each screening test. RESULT: Out
      of eight hundred women with mean age 36.5 +/- 5.94 years undergoing pap smear,
      ASCUS was found in 66(8.25%), ASC-H in 2(0.25%), LSIL in 48(6%), HSIL in 8(1%),
      inflammatory in 540(67.5%). Out of 260 women who underwent HPV DNA testing, 120
      (46.15%) had abnormal cytology and/or positive HPV DNA test (Group I, n = 120)
      and 140(53.8%) had dual negative results (Group II, n = 140) HPV DNA test was
      found positive in 64 women (53.3%) in Group I. Sensitivity and specificity of pap
      smear was 69.2 and 63.72% while for HPV DNA testing was 92.3 and 84%
      respectively. PPV and NPV of pap smear, HPV DNA testing and colposcopy was 18,
      40, 76.4% and 94.7, 98.9, 100% respectively. Diagnostic accuracy of pap smear (k
      = 0.14), HPV DNA test (k = 0.70) and colposcopy (k = 0.81) was 64.29, 84.9, and
      96.8% respectively. Combining pap smear & HPV DNA testing (k = 0.25) increased
      the sensitivity and NPV to 100%. CONCLUSION: Sensitivity and diagnostic accuracy
      of HPV DNA test is more than that of pap smear and the test is not influenced by
      inflammatory conditions of vagina. In low resource settings, women with ASCUS and
      LSIL on cervical cytology should be subjected to HPV DNA test and only if found
      positive should be referred for colposcopy thereby reducing colposcopy referrals.
      Women with HSIL should be directly subjected to colposcopy guided biopsy. Using
      this approach, most of the preinvasive cervical lesion will be detected but few
      cases will still be missed among inflammatory smears, if HPV DNA testing is not
      supplemented.

PMID- 22851829
TI  - A Successful Pregnancy Outcome Following IVF-ICSI Using Cryopreserved Semen from
      a Man with Testicular Tumor.

PMID- 22851830
TI  - Outcome of gender bias: isolated bilateral upper limb amelia.

PMID- 22851831
TI  - Secondary abdominal pregnancy following uterine perforation.

PMID- 22851833
TI  - Good Clinical Practice Recommendations for HIV.

PMID- 22851832
TI  - Deep vein thrombosis following laparoscopic hysterectomy in a nulliparous woman.
AB  - A nulliparous woman aged 45 years was referred to us with painful swelling in
      left lower limb. She underwent laparoscopic hysterectomy for menorrhagia 12 days
      prior to the admission. The laparoscopic surgery was completed in 90 min without
      blood loss and blood transfusion. The size of the uterus was approximately 12
      weeks. Duplex scan of the left lower limb confirmed thrombosis of the left
      external iliac vein, femoral vein, popliteal vein and tibial veins. On
      examination the laparoscopic puncture wounds healed well. She was hospitalized
      for initial anticoagulation with low molecular weight heparin (Enoxapain 1 mg/kg
      body weight twice daily) and compression bandages. Histological examination of
      the hysterectomy specimen was noted to be benign (Adenomyosis and cervical
      Leiomyoma). She responded to anticoagulation therapy and was discharged with an
      advice to attend the follow up clinic for long term anticoagulation advice for
      the next 6 months to prevent recurrent thromboembolic episodes.

PMID- 22851834
TI  - Evolution of endocrine surgery in India.

PMID- 22851835
TI  - Randomised clinical trials in surgery: a look at the ethical and practical
      issues.
AB  - An ethically conducted randomised controlled trial (RCT) is the backbone of
      evidence based medicine. In surgical practice however, RCTs have taken a
      backseat, drawing much adverse comment. There are several reasons to explain
      surgeons' disinclination to conduct RCTs. These include many practical
      difficulties such as the problem of blinding surgical procedures, design and
      funding issues. There are also many ethical issues which need to be considered
      including the concept of equipoise as well as the ethical issues associated with
      sham surgery as a control. While there is no doubt that RCTs are essential and in
      fact have helped to weed out several unnecessary surgical procedures, it is
      important not to lose sight of the fact that they may not be always necessary in
      order to obtain evidence in favour of a procedure. Possible solutions could be to
      follow guidelines that have been issued by learned bodies and a strict adherence
      to all ethical norms that have been recommended in the conduct of trials.

PMID- 22851836
TI  - Controversies and challenging therapeutic modalities in gastric cancer.
AB  - Gastric cancer is still the fourth common neoplasm worldwide. Gastric ulcers,
      adenomatous polyps, and intestinal metaplasia have been associated with an
      increased relative risk. Tissue diagnosis and anatomic localization of the
      primary tumor are best obtained by upper gastrointestinal endoscopy. Despite new
      screening techniques peritoneal tumor spread and occult liver and lymph node
      metastases are only detected intra-operatively. Therapy is becoming more and more
      complex comprising surgical resection, investigational neoadjuvant, adjuvant or
      palliative chemotherapy, or supportive care. Complete surgical eradication of a
      tumor with resection of adjacent lymph nodes represents the best chance for long
      term survival. The choice of operation depends upon the location of the tumor,
      the clinical stage, and the histologic type. Chemotherapy can provide symptom
      palliation, improve quality of life, and prolong survival in patients with
      advanced gastric cancer. Preoperative radiation therapy may allow for tumor
      downstaging and reduced probability of residual microscopic disease at surgery.

PMID- 22851838
TI  - A study of changes in stomach wall at sites other than the ulcer in chronic
      duodenal ulcer patients.
AB  - It is known that at least 90% of duodenal ulcers are caused by infection with the
      bacterium Helicobacter pylori. Eradicating this organism usually results in
      complete resolution of the disease (Rosengren, Br J Gen Pract 46(409):491-492,
      1996). To study the different changes if any in stomach wall at sites other than
      the ulcer in chronic duodenal ulcer patients by upper Gastro-Intenstinal
      Endoscopy followed by histopathological examination of different parts of
      stomach. This study was a retrospective study conducted in the Department of
      General surgery, V.S.S. Medical College, Burla, Sambalpur, odisha during the
      period of June 2007 to May 2009. Subjects were patients with chronic duodenal
      ulcer who underwent endoscopic examination, gastric biopsy and rapid urease test.
      Chronic gastritis of antrum, followed by erythematous pangastritis was the
      prominent feature both in endoscopy and histopathological examination. The
      Inflammatory change affected the mucosa and submucosa of the stomach wall. The
      prevalence rate of Helicobacter pylori was 84%, the antrum being the most common
      affected part (84%) followed by gastric fundus (41%). Chronic superficial
      atrophic gastritis of antrum, followed by pangastritis is the most common
      pathological abnormality in stomach wall in CDU cases. Gastric antrum is the most
      common site for H. pylori colonization followed by fundus. Presence of H. pylori
      in stomach wall is associated with active on chronic gastritis.

PMID- 22851837
TI  - A brief review of common oral premalignant lesions with emphasis on their
      management and cancer prevention.
AB  - Long-term outcomes associated with oral cancer and its management over the past
      several decades has caused concern and the value of mass oral cancer screenings
      has come under scrutiny. Though not all oral carcinomas are preceded by
      premalignant lesions as clinically visible morphological alterations occur
      secondary to the cellular or molecular changes, certain high risk lesions have
      been identified. Their management remains controversially polarized between
      surgical excision to prevent malignant change and conservative medical or
      surveillance techniques. Though oral cancer is one of the "major killers" of
      modern times, there seem to be no widely accepted criteria for decision making in
      clinical practice, the evidence base is scanty and uncertainty persists
      throughout investigation, diagnosis, and treatment. In this article, we have
      briefly discussed the common premalignant lesions, with an emphasis on their
      evidence based management and prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s12262-011-0286-6) contains
      supplementary material, which is available to authorized users.

PMID- 22851839
TI  - Laparoscopic versus open pyeloplasty: comparison of two surgical approaches- a
      single centre experience of three years.
AB  - UPJO causes hydronephrosis and progressive renal impairment may ensue if left
      uncorrected. Open pyeloplasty remains the standard against which new technique
      must be compared. We analyzed the comparison of Laparoscopic and open pyeloplasty
      in a randomized prospective trial. A prospective randomized study was done from
      January 2004 to January 2007 in which a total of 28 Laparoscopic and 34 open
      pyeloplasty were done. All laparoscopic pyeloplasties were performed
      transperitoneally. Standard open Anderson Hynes pyeloplasty, spiral flap or VY
      plasty was done depending on anatomic consideration. Patients were followed with
      DTPA scan at 3 months and IVP at 6 months. Perioperative parameters including
      operative time, analgesic use, hospital stay, and complication and success rates
      were compared. Mean total operative time with stent placement in LP group was
      244.2 min (188-300 min) compared to 122 min (100-140 min) in open group. Compared
      to open pyeloplasty the post operative diclofenac requirement was significantly
      less in LP group (mean107.14 mg) and open group required mean of (682.35 mg) The
      duration of analgesic requirement was also significantly less in LP group. The
      post operative hospital stay in LP was mean 8.29 days (7-11) and was
      significantly less than open group (mean 3.14 Days (2-7 days). Open pyeloplasty
      has been the gold standard for UPJO repair and achieves success rates exceeding
      90%. Laparoscopic pyeloplasty provides a minimally invasive alternative to repair
      UPJO and has developed world wide as the first minimally option to match success
      rate of open pyeloplasty. Its potential advantages including less post op pain,
      shorter hospital stay an improved cosmesis has been proved in some comparative
      series. The only disadvantage seems to be longer operative time. LP has a minimal
      level of morbidity and short hospital stay compared to open approach Although
      Laparoscopic pyeloplasty has the disadvantages of longer operative time and
      requires significant skill of intracorporeal knotting but it is here to stay and
      represents an emerging standard of care.

PMID- 22851840
TI  - Comparative study of glyceryl trinitrate ointment versus surgical management of
      chronic anal fissure.
AB  - Chronic Anal Fissure (CAF) is common perineal condition and well-known painful
      entity. Standard surgical treatment even though available, may require long
      hospital stay and sometimes have worrying complications like anal incontinence.
      So non-surgical treatment, Glyceryl Trinitrate has been shown to be an effective
      for chronic anal fissure. It decreases anal tone and ultimately heals the anal
      fissure. The present study is the attempt to know the efficacy of 0.2% Glyceryl
      Trinitrate ointment in the treatment of chronic anal fissure and to compare the
      effectiveness of 0.2% Glyceryl Trinitrate ointment (GTN) versus fissurectomy with
      lateral internal sphincterotomy (LIS) and fissurectomy with posterior internal
      sphincterotomy (PIS) in the management of chronic anal fissure. This is a
      prospective comparative study of management of chronic anal fissure done in our
      hospital during the period of one and half year from October 2005 to March 2007.
      Thirty patients treated with 0.2% Glyceryl Trinitrate ointment and 30 patients
      treated with fissurectomy and lateral internal sphincterotomy and 30 patients
      treated with posterior internal sphincterotomy, for chronic anal fissure were
      selected for study. A single brand of 0.2% Glyceryl Trinitrate ointment
      (Nitrogesic) used for trial arm. Dose of administration was 1.5 cm to 2 cm in the
      anal canal with device provided by manufacturers of the proprietary preparation
      and applied twice a daily for 12 weeks. Patients were followed up for 12 weeks
      and thereafter evaluated for relief of symptoms in all three groups. Observations
      were recorded at 2 weeks; 6 weeks and 12 weeks of follow up period, regarding
      symptoms like pain and bleeding during defecation, healing of CAF and also for
      side effects like headache in GTN group and flatus, fecal incontinence in
      surgical groups. Data collected in proforma and analyzed. Study revealed CAF was
      more in male 59 patients (66%) than the female 31 patients (34%), the ratio being
      1: 0.52. The maximum number of patients was encountered in the age group of 20 to
      40 years with mean duration of age 34.14 years. In all three groups symptoms like
      pain, bleeding, constipation and sphincter spasm were present. Sentinel pile was
      present in 56% of the patients. Common site of fissure was found to be posterior
      in 94% of patients. Observations with respect to relief of pain, no bleeding and
      healing were recorded at 2, 6 and 12 weeks of duration. Lateral sphincterotomy
      remains effective but should be reserved for the patients who fail to respond to
      initial chemical sphincterotomy or GTN therapy. GTN is good alternative mode of
      therapy for patients who refuse surgery and prefer medical line of treatment.

PMID- 22851841
TI  - Ghee and honey dressing for infected wounds.
AB  - Ghee and honey has been advocated and used as dressing for infected wounds by
      Sushruta (600BC) and since 1991 in four Mumbai Hospitals. The gratifying results
      observed with the dressing have prompted this study which aims to establish its
      efficacy in five recalcitrant subset of chronic infected wounds over a three year
      period 2006-2009. A standardized ghee and honey dressing was used to treat: a)
      Eight cases of fungating malignant lesions. b) Thirteen chronic venous ulcers. c)
      Twenty nine diabetic foot ulcers. d) Eleven of infected ventral hernia mesh
      hernioplasty. e) Eleven patient with post-cesarean wound dehiscence. The dressing
      markedly reduced the foul odour and discharge, significantly improving the
      quality of life in malignant lesions. The results were equivocal in cases of
      venous ulcers. The results were uniformly good in the last three groups. In view
      of our results, as also result of innumerable Randomized Control Trials (RCTs)
      reported on honey dressing for infected wounds, there is substantial evidence
      that ghee and honey dressing has at least comparable results to other modes of
      treatment. The easy availability and low cost of this treatment makes it
      significant in developing countries. Further trials seem warranted.

PMID- 22851842
TI  - The role of mediastinoscopy for diagnosis of isolated mediastinal
      lymphadenopathy.
AB  - To determine the role of mediastinoscopy (MDS) in the histological diagnosis of
      isolated mediastinal lymphadenopathy in a centre where more sophisticated
      investigations, like positron emitting tomography (PET) scan and endobronchial
      ultrasound guided trans-bronchial needle aspiration (EBUS-TBNA) is not available.
      This is a retrospective study. From January 2006 to December 2009, 31 patients
      with isolated mediastinal lymphadenopathy underwent MDS to establish a
      histological diagnosis. The mean age was 36.3 years. Among the patients, 19 were
      males and 12 were females. The most common symptom was dry cough in 18 (58%)
      patients. The diagnostic yield was 96.8%, with sarcoidosis being the commonest
      diagnosis. It was concluded that MDS was vital in establishing a histological
      diagnosis in patients with isolated mediastinal lymphadenopathy.

PMID- 22851843
TI  - A Comparative Study of Fine Needle Aspiration Cytology (FNAC) and Fine Needle Non
      aspiration Cytology (FNNAC) Technique in Lesions of Thyroid Gland.
AB  - The present study was done to compare diagnostic yield by fine needle non
      aspiration technique (FNNAC) with Fine Needle Aspiration cytology (FNAC) of
      lesions in thyroid gland. FNNAC and FNAC both were performed on 69 patients
      presenting with thyroid lesions, except those suffering from thyrotoxicosis.
      Smears were then cytologically interpreted by a single pathologist as unsuitable,
      diagnostically adequate or diagnostically superior for opinion, without the
      knowledge of sampling method employed. Slides were evaluated for following
      aspects namely cellularity, presence of colloid, inflammatory cell, hemosiderin
      laden macrophages, papillary clusters nuclear overlapping, nuclear grooving,
      hurthle cells. FNNAC gave better results in form of better quality of cellularity
      and less field obscurity by blood in lesions of thyroid. Diagnostically superior
      specimens were obtained more frequently by FNNAC, so this technique should be
      used alone or in tandem with FNAC for better diagnostic yield.

PMID- 22851844
TI  - Metallo Beta lactamase producing pseudomonas aeruginosa and its association with
      diabetic foot.
AB  - Pseudomonas aeruginosa strains that produce metallo beta lactamases (MBLs) are
      becoming increasingly prevalent in wound infections. The aim of the present study
      is to determine the clinical features, incidence, and to find out the
      antimicrobial susceptibility pattern of Pseudomonas aeruginosa in diabetic foot
      infections. Pus samples for bacterial culture were collected from 310 patients
      admitted with diabetic foot infections. Antimicrobial sensitivity testing was
      performed by the Kirby-Bauer disc diffusion method. Carbapenem resistance
      screening and confirmation of MBL was done by the modified imipenem
      ethylenediaminetetraacetic acid (EDTA) double disc synergy test. A total of 54
      Pseudomonas aeruginosa was isolated from 310 diabetic foot cases. Males were
      affected more than females with an M:F ratio of 1.6:1. Most patients belonged to
      the fifth decade of life with a mean age of 49 +/- 16.8 years. All the patients
      were previously diagnosed with diabetes mellitus with duration of the disease at
      16 +/- 10.2 years and 63% were prescribed oral hypoglycaemic agents. Wound
      characteristics were classified according to Wagner's classification majority of
      Pseudomonas aeruginosa were isolated from Wagner's II and III grade wound. A
      number of 26 (89.7%) patients underwent debridement, while 9 (31%) patients
      underwent toe disarticulation, and 7 (24.1%) patients underwent below-the-knee
      (BKA) amputation. Antibiotic sensitivity testing revealed 20.3% of Pseudomonas
      aeruginosa were resistance to carbapenem and 81.8% of these were MBL mediated
      resistance. Infection with multi drug resistance organisms (MDROs) is common in
      diabetic foot ulcers and is associated with inadequate glycemic control and
      increased requirement for surgical treatment. There is a need for continuous
      surveillance of resistant bacteria to provide the basis for empirical therapy and
      reduce the risk of complications.

PMID- 22851845
TI  - Enterolith containing uric Acid: an unusual cause of intestinal obstruction.
AB  - Enterolith is a rare clinical entity that may be found on imaging or at surgery.
      We report an unusual case of intestinal obstruction caused by a large uric acid
      containing enterolith which was formed in the absence of any bowel inflammation,
      stricture or diverticulum.

PMID- 22851846
TI  - Recurrent Peptic Ulcer due to Carcinoid Tumour of Jejunum.
AB  - Carcinoid Tumours are classified as Neuro-endocrine tumours. Commonly known
      ulcerogenic neuro-endocrine tumour is Gastrinoma of the Pancreas and Duodenum.It
      secretes hormone Gastrin which causes hyperplasia of the gastric parietal cells
      with excessive secretion of hydrochloric acid resulting in multiple ulcerations
      in the stomach, duodenum and upper jejunum. Carcinoid tumours is not known to
      cause peptic ulceration.

PMID- 22851847
TI  - Malignant tumor at the fourth part of duodenum mimicking wilkie syndrome.

PMID- 22851848
TI  - Isolated gangrene of the penis in a paraplegic patient secondary to a condom
      catheter.
AB  - Isolated gangrene of the penis is rare. Our case was unusual in that gangrene
      developed due to continuous tourniquet effect on the penis caused by a condom
      catheter. Also, men with paraplegia appear to have a greater incidence of
      bacterial colonisation of genital skin as compared to neurologically normal
      controls. Early therapy is the key, including debridement of entire shaft of the
      penis distal to the devasted area, parenteral broad-spectrum antibiotics,
      repeated antiseptic dressings and skin grafting. Early diagnosis by a strong
      index of suspicion ensures a favourable outcome. Since gangrene of the penis is
      an irreversible process, this case highlights the importance of proper care and
      routine maintenance of condom catheters in preventing this complication. Despite
      extensive search of the literature, I have been able to find only few such cases.

PMID- 22851849
TI  - Intramural metastatic squamous cell carcinoma of stomach.
AB  - Intramural metastasis to the stomach (IMMS) from carcinoma esophagus, excluding
      direct invasion and spread to the stomach, is relatively uncommon. Diagnosis of
      IMMS is based on histological criteria, and it is associated with poor prognosis
      (Takubo et al. Cancer 65:1816-1819, 1990]. We report two patients of SCC
      oesophagus in whom intramural metastasis to stomach has occurred.

PMID- 22851850
TI  - Recurrent pyogenic cholangitis treated by left hepatectomy.
AB  - Recurrent pyogenic cholangitis is managed mostly by conservative treatment or by
      clearance of stones and biliary enteric by-pass procedure. Hepatectomy is rarely
      needed. We report a case of recurrent pyogenic cholangitis in a 34-year old man,
      who presented with recurrent upper abdominal pain, mild jaundice, and fever since
      childhood. Contrast enhanced computed tomography of abdomen and magnetic
      resonance cholangiopancreatography confirmed the diagnosis and showed significant
      atrophy of the left lobe of the liver. Patient was treated successfully with left
      hepatectomy and was well at 9 month follow-up.

PMID- 22851851
TI  - Congenital Morgagni's Hernia Presenting in Elderly Lady.
AB  - Morgagni's hernia is an uncommon type of congenital diaphragmatic hernia. Large
      numbers are symptomatic but some may present in middle aged. Our patient was
      asymptomatic till 63 years of age. X-ray chest, for her recent onset exertional
      dyspne, was suspicious of right lung mass. CT thorax revealed right Morgagni's
      type of diaphragmatic hernia, a very rare diagnosis at that age.

PMID- 22851852
TI  - A common trunk of origin of the right testicular and middle suprarenal arteries
      with a retrocaval course.
AB  - A common trunk of origin of the right testicular and middle suprarenal arteries
      with a retrocaval course was observed during the dissection of a male cadaver.
      The Common trunk (CT) arose from the anterior aspect of the abdominal aorta (AA)
      at the level of the right renal artery (RRA) and after a short course behind the
      inferior vena cava (IVC), the CT divided into right testicular and middle
      suprarenal arteries. The middle suprarenal artery (MSA) passed upwards behind the
      IVC to the right suprarenal gland. The right testicular artery (RTA) descended
      posterior to the RRA and anterior to the IVC. It then continued on its normal
      route distally with the right testicular vein. The awareness of such variations
      of testicular and middle suprarenal arteries and their unusual origin and course
      might complicate the interpretation of angiograms and surgical procedures in the
      posterior abdominal area.

PMID- 22851853
TI  - Spontaneous perforation of acalculous gallblader: a case report.
AB  - Main cause of gallbladder perforation is cholecystitis with or without stones. In
      old age, spontaneous perforation of gallbladder can be due to decreased blood
      supply which can be as the result of atherosclerosis, focal vasospasm or
      localized vasculitis. Perforation is associated with high morbidity and mortality
      if left untreated. Here, we report a rare case of idiopathic and spontaneous
      perforation of gallbladder in a 77 years old lady.

PMID- 22851854
TI  - Syndromic rhyme.

PMID- 22851855
TI  - Invasive burn wound infection.

PMID- 22851856
TI  - Metabolic syndrome after liver transplantation: preventable illness or common
      consequence?
AB  - The metabolic syndrome is common after liver transplant being present in
      approximately half of recipients. It has been associated with adverse outcomes
      such as progression of hepatitis C and major vascular events. As the United
      States population ages and the rate of obesity increases, prevention of the
      metabolic syndrome in the post-transplant population deserves special
      consideration. Currently, the metabolic syndrome after transplant appears at
      least two times more common than observed rates in the general population.
      Specific guidelines for patients after transplant does not exist, therefore
      prevention rests upon knowledge of risk factors and the presence of modifiable
      elements. The current article will focus on risk factors for the development of
      the metabolic syndrome after transplant, will highlight potentially modifiable
      factors and propose potential areas for intervention. As in the non-transplant
      population, behavioral choices might have a major role. Opportunities exist in
      this regard for health prevention studies incorporating lifestyle changes. Other
      factors such as the need for immunosuppression, and the changing characteristics
      of wait listed patients are not modifiable, but are important to know in order to
      identify persons at higher risk. Although immunosuppression after transplant is
      unavoidable, the contribution of different agents to the development of
      components of the metabolic syndrome is also discussed. Ultimately, an increased
      risk of the metabolic syndrome after transplant is likely unavoidable, however,
      there are many opportunities to reduce the prevalence.

PMID- 22851858
TI  - Current knowledge on esophageal atresia.
AB  - Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the
      most common congenital anomaly of the esophagus. The improvement of survival
      observed over the previous two decades is multifactorial and largely attributable
      to advances in neonatal intensive care, neonatal anesthesia, ventilatory and
      nutritional support, antibiotics, early surgical intervention, surgical materials
      and techniques. Indeed, mortality is currently limited to those cases with
      coexisting severe life-threatening anomalies. The diagnosis of EA is most
      commonly made during the first 24 h of life but may occur either antenatally or
      may be delayed. The primary surgical correction for EA and TEF is the best option
      in the absence of severe malformations. There is no ideal replacement for the
      esophagus and the optimal surgical treatment for patients with long-gap EA is
      still controversial. The primary complications during the postoperative period
      are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal
      dysmotility, fistula recurrence, respiratory disorders and deformities of the
      thoracic wall. Data regarding long-term outcomes and follow-ups are limited for
      patients following EA/TEF repair. The determination of the risk factors for the
      complicated evolution following EA/TEF repair may positively impact long-term
      prognoses. Much remains to be studied regarding this condition. This manuscript
      provides a literature review of the current knowledge regarding EA.

PMID- 22851859
TI  - Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of
      24 cases.
AB  - AIM: To investigate the clinicopathological features of intraductal neoplasm of
      the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24
      cases of INihB, which were previously diagnosed as biliary papillomatosis or
      intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin
      immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki
      67, P53 and beta-catenin immunoreactivity were also examined. We categorized each
      tumor as adenoma (low grade), borderline (intermediate grade), and malignant
      (carcinoma in situ, high grade including tumors with microinvasion). RESULTS:
      Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were
      composed of a papillary structure; the same feature observed in intraductal
      papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four
      tumors (17%) showed both tubular and papillary structures. In three of the four
      tumors (75%), macroscopic mucin secretion was limited but microscopic
      intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant,
      three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found
      in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not
      expressed in the borderline/adenoma group but was expressed only in malignant
      lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the
      malignant group than in the borderline/adenoma group (22.2 +/- 15.5 vs 7.5 +/-
      6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline
      significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of
      beta-catenin was observed in two (8%) of the 24 tumors, and these two tumors also
      showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of
      INihB have a tubular structure, and are subcategorized as IPNB with tubular
      structure. MUC1 expression in INihB correlates positively with degree of
      malignancy.

PMID- 22851857
TI  - Cellular and molecular mechanisms of intestinal fibrosis.
AB  - Fibrosis is a chronic and progressive process characterized by an excessive
      accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring
      of the involved tissue. Intestinal fibrosis may develop in several different
      enteropathies, including inflammatory bowel disease. It develops through complex
      cell, extracellular matrix, cytokine and growth factor interactions. Distinct
      cell types are involved in intestinal fibrosis, such as resident mesenchymal
      cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM
      producing cells derived from epithelial and endothelial cells (through a process
      termed epithelial- and endothelial-mesenchymal transition), stellate cells,
      pericytes, local or bone marrow-derived stem cells. The most important soluble
      factors that regulate the activation of these cells include cytokines,
      chemokines, growth factors, components of the renin-angiotensin system,
      angiogenic factors, peroxisome proliferator-activated receptors, mammalian target
      of rapamycin, and products of oxidative stress. It soon becomes clear that
      although inflammation is responsible for triggering the onset of the fibrotic
      process, it only plays a minor role in the progression of this condition, as
      fibrosis may advance in a self-perpetuating fashion. Definition of the cellular
      and molecular mechanisms involved in intestinal fibrosis may provide the key to
      developing new therapeutic approaches.

PMID- 22851860
TI  - Study of human B7 homolog 1 expression in patients with hepatitis B virus
      infection.
AB  - AIM: To further investigate the role of human B7 homolog 1 (B7-H1) in the
      mechanism of persistent hepatitis B virus (HBV) infection. METHODS: Peripheral
      and intra-hepatic B7-H1 expression were compared by flow cytometry and
      immunochemical staining between two 2 distinct groups, one being chronic HBV
      tolerance patients (CHB-T) and the other being acute hepatitis B patients (AHB).
      B7-H1 mRNA expression level was also compared by real time polymerase chain
      reaction between CHB-T and AHB patients. The location of intra-hepatic B7-H1 and
      CD40 expression were analyzed by immunofluorescence. The levels of B7-H1 and CD40
      expression on cultured myeloid dendritic cells (mDCs) with or without hepatitis B
      surface antigen (HBsAg) treatment were analyzed dynamically by flow cytometry.
      Intracellular interferon-gamma (IFN-gamma) staining and the stimulatory capacity
      of mDC of cultured mDC with or without HBsAg treatment were also compared by flow
      cytometry. RESULTS: Peripheral B7-H1 expression on mDCs was increased
      significantly in AHB compared to CHB-T patients (P < 0.05). In the liver tissues
      from CHB-T patients, B7-H1 positive cells were almost absent despite a
      persistently elevated serum HBsAg load. In contrast, there were indeed increased
      B7-H1-positive cells in situ in the liver tissue from AHB. In vitro analysis
      showed the parallel upregulation of B7-H1 and CD40 on CD11c+ mDCs after the onset
      of stimulation. Addition of recombinant hepatitis B surface antigen (rHBsAg)
      significantly decreased CD40 expression (P < 0.05 at 16 h, 20 h and 24 h time
      points). B7-H1 expression was also inhibited by rHBsAg, and the inhibition rate
      of CD40 was greater than that of B7-H1. This preferential inhibition of CD40
      expression on mDCs by rHBsAg resulted in the dysfunction of mDCs and T cells in
      the mixed leucocyte reaction (MLR) system. With rHBsAg pretreatment, in a
      carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled MLR system at a
      ratio of 1:5 responder cell-stimulator cell (R/S), the CFSE(dim) percentage of T
      cells decreased from 85.1% to 25.4% and decreased from 30.3% to 12.0% at 1:10
      R/S. IFN-gamma production by CD8+ T cells, in the MLR system, was reduced
      significantly by HBsAg pretreatment. At ratios of 1:5 R/S, the percentage of IFN
      gamma and CD8 dual positive T cells decreased from 55.2% +/- 5.3% to 15.1% +/-
      3.1% (P < 0.001), and decreased from 35.0% +/- 5.1% to 7.3% +/- 2.7% at ratios of
      1:10 R/S (P < 0.001). CONCLUSION: B7-H1 is not a signature of immune dysfunction,
      but an inflammation marker. HBsAg regulate immune response by tipping the balance
      between B7-H1 and CD40.

PMID- 22851861
TI  - Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate
      cells results in decreased secretion of IL-6.
AB  - AIM: To investigate the mechanism of interleukin (IL)-6 secretion through
      blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short
      hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro. METHODS: HSCs were
      derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was
      evaluated using real-time quantitative polymerase chain reaction and enzyme
      linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated
      protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon
      induction by IL-17A and suppression by IL-17RA shRNA were examined using Western
      blotting. RESULTS: IL-6 expression induced by IL-17A was significantly increased
      compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of
      IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL
      17A compared to group with only IL-17A treatment (1.44 +/- 0.17 vs 4.07 +/- 0.43,
      P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5
      min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and
      ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A
      (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific
      inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups
      without inhibitors preincubation (1.67 +/- 0.24, 2.01 +/- 0.10 vs 4.08 +/- 0.59,
      P < 0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced
      IL-6 mRNA expression compared to random shRNA in HSCs (1.44 +/- 0.17 vs 3.98 +/-
      0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of
      p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION:
      Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression
      induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of
      IL-17RA expression may be a strategy to reduce the inflammatory response induced
      by IL-17A in the liver.

PMID- 22851862
TI  - ERCP for the treatment of bile leak after partial hepatectomy and fenestration
      for symptomatic polycystic liver disease.
AB  - AIM: To describe endoscopic treatment of bile leaks in these patients and to
      identify risk factors in these patients which can predict the development of bile
      leaks. METHODS: Retrospective case-control study examining consecutive patients
      who underwent partial hepatectomy for polycystic liver disease (PLD) and
      developed a postoperative bile leak managed endoscopically over a ten year
      period. Each case was matched with two controls with PLD who did not develop a
      postoperative bile leak. RESULTS: Ten cases underwent partial hepatectomy with
      fenestration for symptoms including abdominal distention, pain and nausea.
      Endoscopic retrograde cholangiopancreatography (ERCP) showed anatomic
      abnormalities in 1 case. A biliary sphincterotomy was performed in 4 cases. A
      plastic biliary stent was placed with the proximal end at the site of the leak in
      9 cases; in 1 case two stents were placed. The overall success rate of ERCP to
      manage the leak was 90%. There were no significant differences in age, gender,
      comorbidities, duration of symptoms, history of previous surgery or type of
      surgery performed between cases and controls. CONCLUSION: ERCP with stent
      placement is safe and effective for management of post-hepatectomy bile leak in
      patients with PLD.

PMID- 22851863
TI  - Physical activity, obesity and gastroesophageal reflux disease in the general
      population.
AB  - AIM: To clarify the association between physical activity and gastroesophageal
      reflux disease (GERD) in non-obese and obese people. METHODS: A Swedish
      population-based cross-sectional survey was conducted. Participants aged 40-79
      years were randomly selected from the Swedish Registry of the Total Population.
      Data on physical activity, GERD, body mass index (BMI) and the covariates age,
      gender, comorbidity, education, sleeping problems, and tobacco smoking were
      obtained using validated questionnaires. GERD was self-reported and defined as
      heartburn or regurgitation at least once weekly, and having at least moderate
      problems from such symptoms. Frequency of physical activity was categorized into
      three groups: (1) "high" (several times/week); (2) "intermediate" (approximately
      once weekly); and (3) "low" (1-3 times/mo or less). Analyses were stratified for
      participants with "normal weight" (BMI < 25 kg/m2), "overweight" (BMI 25 to <= 30
      kg/m2) and "obese" (BMI > 30 kg/m2). Multivariate logistic regression was used to
      calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for
      potential confounding by covariates. RESULTS: Of 6969 eligible and randomly
      selected individuals, 4910 (70.5%) participated. High frequency of physical
      activity was reported by 2463 (50%) participants, GERD was identified in 472
      (10%) participants, and obesity was found in 680 (14%). There were 226 (5%)
      individuals with missing information about BMI. Normal weight, overweight and
      obese participants were similar regarding distribution of gender and tobacco
      smoking status, while obese participants were on average slightly older, had
      fewer years of education, more comorbidity, slightly more sleeping problems,
      lower frequency of physical activity, and higher occurrence of GERD. Among the
      2146 normal-weight participants, crude point estimates indicated a decreased risk
      of GERD among individuals with high frequency of physical activity (OR: 0.59, 95%
      CI: 0.39-0.89), compared to low frequency of physical activity. However, after
      adjustment for potential confounding factors, neither intermediate (OR: 1.30, 95%
      CI: 0.75-2.26) nor high (OR: 0.99, 95% CI: 0.62-1.60) frequency of physical
      activity was followed by decreased risk of GERD. Sleeping problems and high
      comorbidity were identified as potential confounders. Among the 1859 overweight
      participants, crude point estimates indicated no increased or decreased risk of
      GERD among individuals with intermediate or high frequency of physical activity,
      compared to low frequency. After adjustment for confounding, neither intermediate
      (OR: 0.75, 95% CI: 0.46-1.22) nor high frequency of physical activity were
      followed by increased or decreased risk of GERD compared to low frequency among
      nonobese participants. Sleeping problems and high comorbidity were identified as
      potential confounders for overweight participants. In obese individuals, crude
      ORs were similar to the adjusted ORs and no particular confounding factors were
      identified. Intermediate frequency of physical activity was associated with a
      decreased occurrence of GERD compared to low frequency of physical activity
      (adjusted OR: 0.41, 95% CI: 0.22-0.77). CONCLUSION: Intermediate frequency of
      physical activity might decrease the risk of GERD among obese individuals, while
      no influence of physical activity on GERD was found in non-obese people.

PMID- 22851864
TI  - Irritable bowel syndrome: physicians' awareness and patients' experience.
AB  - AIM: To study if and how physicians use the irritable bowel syndrome (IBS)
      diagnostic criteria and to assess treatment strategies in IBS patients. METHODS:
      A questionnaire was sent to 191 physicians regarding IBS criteria, diagnostic
      methods and treatment. Furthermore, 94 patients who were diagnosed with IBS
      underwent telephone interview. RESULTS: A total of 80/191 (41.9%) physicians
      responded to the survey. Overall, 13 patients were diagnosed monthly with IBS by
      specialists in gastroenterology (SGs) and 2.5 patients by general practitioners
      (GPs). All the SGs knew of the criteria to diagnose IBS, as did 46/70 (65.7%)
      GPs. Seventy-nine percent used the patient's history, 38% used a physical
      examination, and 38% exclusion of other diseases to diagnose IBS. Only 18/80
      (22.5%) physicians used specific IBS criteria. Of the patients interviewed, 59/94
      (62.8%) knew they had experienced IBS. Two out of five patients knew IBS and had
      seen a physician because of IBS symptoms. Half of those received a diagnosis of
      IBS. A total of 13% were satisfied with treatment. IBS affected daily activities
      in 43% of cases. CONCLUSION: Half of the patients with IBS who consulted a
      physician received a diagnosis. Awareness and knowledge of diagnostic criteria
      for IBS differ between SGs and GPs.

PMID- 22851865
TI  - Assessment of the validity of the clinical pathway for colon endoscopic
      submucosal dissection.
AB  - AIM: To determine the effective hospitalization period as the clinical pathway to
      prepare patients for endoscopic submucosal dissection (ESD). METHODS: This is a
      retrospective observational study which included 189 patients consecutively
      treated by ESD at the National Cancer Center Hospital from May 2007 to March
      2009. Patients were divided into 2 groups; patients in group A were discharged in
      5 d and patients in group B included those who stayed longer than 5 d. The
      following data were collected for both groups: mean hospitalization period, tumor
      site, median tumor size, post-ESD rectal bleeding requiring urgent endoscopy,
      perforation during or after ESD, abdominal pain, fever above 38   degrees C, and
      blood test results positive for inflammatory markers before and after ESD. Each
      parameter was compared after data collection. RESULTS: A total of 83% (156/189)
      of all patients could be discharged from the hospital on day 3 post-ESD.
      Complications were observed in 12.1% (23/189) of patients. Perforation occurred
      in 3.7% (7/189) of patients. All the perforations occurred during the ESD
      procedure and they were managed with endoscopic clipping. The incidence of post
      operative bleeding was 2.6% (5/189); all the cases involved rectal bleeding. We
      divided the subjects into 2 groups: tumor diameter >= 4 cm and < 4 cm; there was
      no significant difference between the 2 groups (P = 0.93, chi2 test with Yates
      correction). The incidence of abdominal pain was 3.7% (7/189). All the cases
      occurred on the day of the procedure or the next day. The median white blood cell
      count was 6800 +/- 2280 (cells/MUL; +/- SD) for group A, and 7700 +/- 2775
      (cells/MUL; +/- SD) for group B, showing a statistically significant difference
      (P = 0.023, t-test). The mean C-reactive protein values the day after ESD were
      0.4 +/- 1.3 mg/dL and 0.5 +/- 1.3 mg/dL for groups A and B, respectively, with no
      significant difference between the 2 groups (P = 0.54, t-test). CONCLUSION: One
      day admission is sufficient in the absence of complications during ESD or early
      post-operative bleeding.

PMID- 22851866
TI  - Analysis of hepcidin expression: in situ hybridization and quantitative
      polymerase chain reaction from paraffin sections.
AB  - AIM: To establish methods for quantitative polymerase chain reaction (PCR) for
      hepcidin using RNAs isolated from paraffin-embedded sections and in situ
      hybridization of hepatocellular carcinoma (HCC). METHODS: Total RNA from paraffin
      embedded sections was isolated from 68 paraffin-embedded samples of HCC. Samples
      came from 54 male and 14 female patients with a mean age of 66.8 +/- 7.8 years.
      Quantitative PCR was performed. Immunohistochemistry and in situ hybridization
      for hepcidin were also performed. RESULTS: Quantitative PCR for hepcidin using
      RNAs isolated from paraffin-embedded sections of HCC was performed successfully.
      The expression level of hepcidin mRNA in cancer tissues was significantly higher
      than that in non-cancer tissues. A method of in situ hybridization for hepcidin
      was established successfully, and this demonstrated that hepcidin mRNA was
      expressed in non-cancerous tissue but absent in cancerous tissue. CONCLUSION: We
      have established novel methods for quantitative PCR for hepcidin using RNAs
      isolated from paraffin-embedded sections and in situ hybridization of HCC.

PMID- 22851867
TI  - Double layered self-expanding metal stents for malignant esophageal obstruction,
      especially across the gastroesophageal junction.
AB  - AIM: To evaluate the clinical outcomes of double-layered self-expanding metal
      stents (SEMS) for treatment of malignant esophageal obstruction according to
      whether SEMS crosses the gastroesophageal junction (GEJ). METHODS: Forty eight
      patients who underwent the SEMS insertion for malignant esophageal obstruction
      were enrolled. Patients were classified as GEJ group (SEMS across GEJ, 18
      patients) and non-GEJ group (SEMS above GEJ, 30 patients) according to SEMS
      position. Double layered (outer uncovered and inner covered stent) esophageal
      stents were placed. RESULTS: The SEMS insertion and the clinical improvement were
      achieved in all patients in both groups. Stent malfunction occurred in seven
      patients in the GEJ group and nine patients in the non-GEJ group. Tumor
      overgrowth occurred in five and eight patients, respectively, food impaction
      occurred in one patient in each group, and stent migration occurred in one and no
      patient, respectively. There were no significant differences between the two
      groups. Reflux esophagitis occurred more frequently in the GEJ group (eight vs
      five patients, P = 0.036) and was controlled by proton pump inhibitor. Aspiration
      pneumonia occurred in zero and five patients, respectively, and tracheoesophageal
      fistula occurred in zero and two patients, respectively. CONCLUSION: Double
      layered SEMS are a feasible and effective treatment when placed across the GEJ
      for malignant esophageal obstruction. Double-layered SEMS provide acceptable
      complications, especially migration, although reflux esophagitis is more common
      in the GEJ group.

PMID- 22851868
TI  - Vitamin D deficiency: correlation to interleukin-17, interleukin-23 and PIIINP in
      hepatitis C virus genotype 4.
AB  - AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients
      and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide
      of type III pro-collagen (PIIINP) as immune response mediators. METHODS: The
      study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C
      virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the
      Endemic Disease Hospital at Cairo University. Patients were compared with 25 age-
      and sex-matched healthy individuals. Inclusion criteria were based on a history
      of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under
      follow-up). Based on ultrasonography, patients were classified into four
      subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with
      hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).
      Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH)2-Vit D] assays
      were carried out using commercial kits. IL-17, IL-23 and PIIINP levels were
      assayed using enzyme linked immunosorbent assay kits, while HCV virus was
      measured by quantitative and qualitative polymerase chain reaction. RESULTS:
      Levels of Vit D and its active form were significantly lower in advanced liver
      disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with
      bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PIIINP levels were
      markedly increased in HCV patients and correlated with the progression of hepatic
      damage. The decrease in Vit D and active Vit D was concomitant with an increase
      in viral load, as well as levels of IL-17, IL-23 and PIIINP among all subgroups
      of HCV-infected patients, compared to normal healthy controls. A significant
      negative correlation was evident between active Vit D and each of IL-17, IL-23
      and PIIINP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV
      infected men and women showed no differences with respect to Vit D levels. The
      viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and 
      0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23
      and PIIINP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the
      deficiency in Vit D was related to HCV-induced chronic liver disease or was a
      predisposing factor for a higher viral load remains to be elucidated. CONCLUSION:
      The negative correlations between Vit D and IL-17, IL-23 and PIIINP highlight
      their involvement in the immune response in patients with HCV-4-related liver
      diseases in Egypt.

PMID- 22851869
TI  - PI3K expression and PIK3CA mutations are related to colorectal cancer metastases.
AB  - AIM: To assess the significance of phosphatidylinositol 3-kinase (PI3K) in
      colorectal cancer (CRC) and toxicity of LY294002 in CRC cells with different
      metastatic abilities. METHODS: Sixty formalin-fixed and paraffin-embedded CRC
      tumor specimens were investigated. Adjacent normal colonic mucosa specimens from
      10 of these cases were selected as controls. PI3K protein was detected by
      immunohistochemistry and PIK3CA mutations were investigated by gene sequencing
      analysis. A flow-cytometry-based apoptosis detection kit was used to determine
      PI3K inhibitor-induced apoptosis in CRC cell lines SW480 and SW620. Expression of
      phosphorylated protein kinase B in CRC cell lines was detected by Western
      blotting. RESULTS: There was a significant difference in the proportion of
      primary lesions (30%, 18/60) vs metastatic lesions (46.7%, 28/60) that were
      positive for PI3K (P < 0.05). Mutations were detected in exon 9 (13.3%) and exon
      20 (8.3%). Out of 60 cases, seven mutations were identified: two hotspot
      mutations, C.1633G>A resulting in E545A, and C.3140A>G resulting in H1047R; two
      novel missense mutations C.1624G>A and C.3079G>A; and three synonymous mutations
      (C.1641G>A, C.1581C>T and C.3027T>A). Exposure of SW480 cells to PI3K inhibitor
      for 48 h resulted in a significant increase of apoptotic cells in a dose
      dependent manner [3.2% apoptotic cells in 0 MUmol/L, 4.3% in 5 MUmol/L, 6.3% in
      10 MUmol/L (P < 0.05), and 6.7% in 20 MUmol/L (P < 0.05)]. Moreover, PI3K
      inhibitor induced a similar significant increase of apoptotic cells in the SW620
      cell line for 48 h [3.3% apoptotic cells in 0 MUmol/L, 13.3% in 5 MUmol/L (P <
      0.01), 19.2% in 10 MUmol/L (P < 0.01), and 21.3% in 20 MUmol/L (P < 0.01)].
      CONCLUSION: High PI3K expression is associated with CRC metastasis. PI3K
      inhibitor induced apoptosis in CRC cells and displayed strong cytotoxicity for
      highly metastatic cells. PI3K inhibition may be an effective treatment for CRC.

PMID- 22851871
TI  - Computed tomography virtual endoscopy with angiographic imaging for the treatment
      of type IV-A choledochal cyst.
AB  - Type IV-A choledochal cysts (CCs) are a congenital biliary anomaly which involve
      dilatation of the extrahepatic and intrahepatic bile ducts. We present the case
      of a 30-year-old woman with type IV-A CC, on whom three-dimensional computed
      tomography (3D CT) and virtual endoscopy were performed. 3D CT revealed partial
      dilatation in the posterior branch of the intrahepatic bile duct and a relative
      stricture between it and the extrahepatic bile duct. Virtual endoscopy showed
      that this stricture was membrane-like and separated from the surrounding blood
      vessels. Based on these image findings, complete cyst resection, bile duct plasty
      for the stricture, and hepaticojejunostomy were safely performed. To the best of
      our knowledge, there are no reports of imaging by virtual endoscopy of the
      biliary tract which show the surrounding blood vessels running along the bile
      duct.

PMID- 22851870
TI  - Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat
      plate bioreactor.
AB  - AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL)
      system in the treatment of acute liver failure. METHODS: Canine models with acute
      liver failure were introduced with intravenous administration of D-galactosamine.
      The animals were divided into: the HBAL treatment group (n = 8), in which the
      canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment
      group (n = 8), in which the canines received a 3-h treatment of BAL; the non
      bioartificial liver (NBAL) treatment group (n = 8), in which the canines received
      a 3-h treatment of NBAL; the control group (n = 8), in which the canines received
      no additional treatment. Biochemical parameters and survival time were
      determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV)
      and reverse transcriptase (RT) activity in the plasma were detected. RESULTS:
      Biochemical parameters were significantly decreased in all treatment groups. The
      TBIL level in the HBAL group was lower than that in other groups (2.19 +/- 0.55
      MUmol/L vs 24.2 +/- 6.45 MUmol/L, 12.47 +/- 3.62 MUmol/L, 3.77 +/- 1.83 MUmol/L,
      P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly
      shorter than the NBAL and control groups (18.47 +/- 4.41 s, 15.5 +/- 1.56 s vs
      28.67 +/- 5.71 s, 21.71 +/- 3.4 s, P < 0.05), and the PT in the HBAL group was
      shortest of all the groups. The albumin in the BAL and HBAL groups significantly
      increased and a significantly higher level was observed in the HBAL group
      compared with the BAL group (27.7 +/- 1.7 g/L vs 25.24 +/- 1.93 g/L). In the HBAL
      group, the ammonia levels significantly decreased from 54.37 +/- 6.86 to 37.75 +/
      6.09 after treatment (P < 0.05); there were significant difference in ammonia
      levels between other the groups (P < 0.05). The levels of antibodies were similar
      before and after treatment. The PERV RNA and the RT activity in the canine plasma
      were all negative. CONCLUSION: The HBAL showed great efficiency and safety in the
      treatment of acute liver failure.

PMID- 22851872
TI  - Direct cholangioscopy combined with double-balloon enteroscope-assisted
      endoscopic retrograde cholangiopancreatography.
AB  - Double-balloon enteroscope (DBE)-assisted endoscopic retrograde
      cholangiopancreatography (ERCP) is an effective endoscopic approach for
      pancreatobiliary disorders in patients with altered gastrointestinal anatomy.
      Endoscopic interventions via DBE in these postoperative settings remain difficult
      because of the lack of an elevator and the use of extra-long ERCP accessories.
      Here, we report the usefulness of direct cholangioscopy with an ultra-slim
      gastroscope during DBE-assisted ERCP. Three patients with choledocholithiasis in
      postoperative settings (two patients after Billroth II gastrojejunostomy and one
      patient after Roux-en-Y gastrojejunostomy) were treated. DBE was used to gain
      access to the papilla under carbon dioxide insufflation, and endoscopic
      sphincterotomy was performed with a conventional sphincterotome. For direct
      cholangioscopy, the enteroscope was exchanged for an ultra-slim gastroscope
      through an incision in the overtube, which was inserted directly into the bile
      duct. Direct cholangioscopy was used to extract retained bile duct stones in two
      cases and to confirm the complete clearance of stones in one case. Bile duct
      stones were eliminated with a 5-Fr basket catheter under direct visual control.
      No adverse events were noted in any of the three cases. Direct cholangioscopy
      with an ultra-slim gastroscope facilitates subsequent treatment within the bile
      duct. This procedure represents another potential option during DBE-assisted
      ERCP.

PMID- 22851873
TI  - Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis
      induced portal hypertension.
AB  - A 75-year old man had been diagnosed at 42 years of age as having polycythemia
      vera and had been monitored at another hospital. Progression of anemia had been
      recognized at about age 70, and the patient was thus referred to our center in
      2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy
      findings. Hematemesis due to rupture of esophageal varices occurred in January
      and February of 2011. The bleeding was stopped by endoscopic variceal ligation.
      Furthermore, in March of the same year, hematemesis recurred and the patient was
      transported to our center. He was in irreversible hemorrhagic shock and died. The
      autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers, an
      observation consistent with myelofibrosis. The liver weighed 1856 g the spleen
      1572 g, indicating marked hepatosplenomegaly. The liver and spleen both showed
      extramedullary hemopoiesis. Myelofibrosis is often complicated by portal
      hypertension and is occasionally associated with gastrointestinal hemorrhage due
      to esophageal varices. A patient diagnosed as having myelofibrosis needs to be
      screened for esophageal/gastric varices. Myelofibrosis has a poor prognosis.
      Therefore, it is necessary to carefully decide the therapeutic strategy in
      consideration of the patient's concomitant conditions, treatment invasiveness and
      quality of life.

PMID- 22851874
TI  - Grassroots clinical research using crowdsourcing.

PMID- 22851875
TI  - Treatment of a patient with post-natal chronic calf pain utilizing instrument
      assisted soft tissue mobilization: a case study.
AB  - Musculoskeletal pain is commonly reported by pre- and postnatal women, with the
      most common complaint being low back pain. However, lower leg pain is also
      frequently reported by women particularly in the third trimester. The purpose of
      the case study is to illustrate how instrument-assisted soft tissue mobilization
      (ISTM) can be used to treat a patient with a 2-year history of chronic calf pain.
      The subject was a 35-year-old female who developed calf pain during the last
      trimester of her pregnancy following severe lower leg edema. The calf pain was
      present for the 2 years following delivery and was described as a dull ache,
      typically aggravated by direct pressure on the calf, prolonged standing, and
      stairs. An X-ray, magnetic resonance imaging (MRI) with contrast, and ultrasound
      Doppler study prior to referral ruled out tumors, vascular, lymphatic, or
      skeletal bone abnormalities. However, her MRI did show a dense superficial venous
      tissue asymmetry in the same location of her symptoms. Impairments were minimal;
      the only asymmetrical objective findings were calf length, strength, and soft
      tissue restrictions detected on palpation. After nine treatments incorporating an
      ISTM approach, soft tissue mobility, pain, calf strength, and lower extremity
      functional scale score all improved and her symptoms were abolished.

PMID- 22851876
TI  - Effectiveness of manual physical therapy in the treatment of cervical
      radiculopathy: a systematic review.
AB  - STUDY DESIGN: Systematic review of randomized clinical trials. OBJECTIVE: Review
      of current literature regarding the effectiveness of manual therapy in the
      treatment of cervical radiculopathy. BACKGROUND: Cervical radiculopathy (CR) is a
      clinical condition frequently encountered in the physical therapy clinic.
      Cervical radiculopathy is a result of space occupying lesions in the cervical
      spine: either cervical disc herniations, spondylosis, or osteophytosis. These
      affect the pain generators of bony and ligamentous tissues, producing radicular
      symptoms (i.e. pain, numbness, weakness, paresthesia) observed in the upper
      extremity of patients with cervical nerve root pathology. Cervical radiculopathy
      has a reported annual incidence of 83.2 per 100 000 and an increased prevalence
      in the fifth decade of life among the general population. RESULTS: Medline and
      CINAHL via EBSCO, Cochrane Library, and Google Scholar were used to retrieve the
      randomized clinical trial studies for this review between the years of 1995 and
      February of 2011. Four studies met inclusion criteria and were considered to be
      high quality (PEDro scores of ?5). Manual therapy techniques included muscle
      energy techniques, non-thrust/thrust manipulation/mobilization of the cervical
      and/or thoracic spine, soft-tissue mobilization, and neural mobilization. In each
      study, manual therapy was either a stand-alone intervention or part of a
      multimodal approach which included therapeutic exercise and often some form of
      cervical traction. Although no clear cause and effect relationship can be
      established between improvement in radicular symptoms and manual therapy, results
      are generally promising. CONCLUSION: Although a definitive treatment progression
      for treating CR has not been developed a general consensus exists within the
      literature that using manual therapy techniques in conjunction with therapeutic
      exercise is effective in regard to increasing function, as well as AROM, while
      decreasing levels of pain and disability. High quality RCTs featuring control
      groups are necessary to establish clear and effective protocols in the treatment
      of CR.

PMID- 22851877
TI  - The neurophysiological effects of a single session of spinal joint mobilization:
      does the effect last?
AB  - Studies detailing the neurophysiological effects of spinal manual therapy have
      fueled a paradigm shift away from a strict biomechanical model. However, a recent
      systematic review of the temporal nature of a single session of spinal thrust
      manipulation found that the neurophysiological effects were only temporary. The
      objective of this review was to examine the temporal nature of neurophysiological
      effects after one session of spinal mobilization. Studies eligible for this
      review had to report on the temporal component of the neurophysiological effects
      of a single session of joint mobilization of the spine in human subjects. In
      order to be sure that the temporal nature of these effects was captured, the
      studies had to monitor neurophysiological effects for a time beyond the immediate
      post-treatment period. This systematic review followed the methodology for
      preferred reporting items for systematic reviews and meta-analyses. In order to
      assess the quality, strength, and importance of the included studies, the grading
      of recommendations assessment, development and evaluation system was used.
      Results of this review showed that the neurophysiological effects of a single
      session of spinal mobilization are mostly 5 minutes or less. An exception to
      these findings is hypoalgesia which may last up to 24 hours, based on one study.
      Continued research on small samples of healthy subjects with irrelevant immediate
      outcomes like salivary rate, skin conductance, and skin temperature should give
      way to randomized controlled trials on subjects with pain and decreased function.

PMID- 22851879
TI  - Biomechanical measures of knee joint mobilization.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to quantify the
      biomechanical properties of specific manual therapy techniques in patients with
      symptomatic knee osteoarthritis. METHODS: Twenty subjects (7 female/13 male, age
      54+/-8 years, ht 1.7+/-0.1 m, wt 94.2+/-21.8 kg) participated in this study. One
      physical therapist delivered joint mobilizations (tibiofemoral extension and
      flexion; patellofemoral medial-lateral and inferior glide) at two grades
      (Maitland's grade III and grade IV). A capacitance-based pressure mat was used to
      capture biomechanical characteristics of force and frequency during 2 trials of
      15 second mobilizations. Statistical analysis included intraclass correlation
      coefficient (ICC(3,1)) for intrarater reliability and 2*4 repeated measures
      analyses of variance and post-hoc comparison tests. RESULTS: Force (Newtons)
      measurements (mean, max.) for grade III were: extension 45, 74; flexion 39, 61;
      medial-lateral glide 20, 34; inferior glide 16, 27. Force (Newtons) measurements
      (mean, max.) for grade IV were: extension 57, 76; flexion 47, 68; medial-lateral
      glide 23, 36; inferior glide 18, 35. Frequency (Hz) measurements were between 0.9
      and 1.2 for grade III, and between 2.1 and 2.4 for grade IV. ICCs were above 0.90
      for almost all measures. DISCUSSION AND CONCLUSION: Maximum force measures were
      between the ranges reported for cervical and lumbar mobilization at similar
      grades. Mean force measures were greater at grade IV than III. Oscillation
      frequency and peak-to-peak amplitude measures were consistent with the grade
      performed (i.e. greater frequency at grade IV, greater peak-to-peak amplitude at
      grade III). Intrarater reliability for force, peak-to-peak amplitude and
      oscillation frequency for knee joint mobilizations was excellent.

PMID- 22851878
TI  - The role of MRI in musculoskeletal practice: a clinical perspective.
AB  - This clinical perspective presents an overview of current and potential uses for
      magnetic resonance imaging (MRI) in musculoskeletal practice. Clinical practice
      guidelines and current evidence for improved outcomes will help providers
      determine the situations when an MRI is indicated. The advanced competency
      standard of examination used by physical therapists will be helpful to prevent
      overuse of musculoskeletal imaging, reduce diagnostic errors, and provide the
      appropriate clinical context to pathology revealed on MRI. Physical therapists
      are diagnostically accurate and appropriately conservative in their use of MRI
      consistent with evidence-based principles of diagnosis and screening.

PMID- 22851881
TI  - Letter to the editor.

PMID- 22851880
TI  - Clinician's ability to identify neck and low back interventions: an inter-rater
      chance-corrected agreement pilot study.
AB  - OBJECTIVE: To estimate inter-rater agreement of physical therapists trained in
      MDT approach and participating in practice-based evidence (PBE) research to
      identify 72 physical therapy interventions in video demonstrations on a single
      model and clinical vignettes. PBE is a well designed observational study and
      demonstrating clinician observational consistency is an important step in
      conducting PBE research design. METHODS: Two physical therapists volunteered to
      participate in pilot reliability testing and seven other physical therapists
      trained in McKenzie Mechanical Diagnosis and Therapy (MDT) methods volunteered
      for the inter-rater chance-corrected agreement study. All therapists identified
      interventions presented within 52 videos and 5 written clinical vignettes
      describing 20 more intervention techniques. Therapists independently identified
      all interventions. We assessed inter-rater chance-corrected agreement of
      therapists' ability to identify intervention techniques using Kappa coefficients
      with associated 95% confidence intervals and indices for bias and prevalence.
      RESULTS: Of the 147 kappa coefficients estimated, 7% were ?0.6, 10% were >0.6 and
      ?0.8, and 83% were >0.8. Agreement was lowest for identifying cognitive
      behavioral techniques (median kappa = 0.79). The minimum and maximum prevalence
      and bias indices were 0.33 and 0.85 and 0 and 0.33, respectively suggesting kappa
      coefficient estimates were strong. Generalized kappa coefficients ranged from
      0.73 to 1.00. DISCUSSION: Results provide evidence that substantial to almost
      perfect inter-rater agreement could be expected when trained therapists identify
      physical therapy interventions used for patients with spinal impairments from
      staged videos and vignettes. This may be helpful to reassure clinicians of the
      quality of the reporting of intervention(s) performed when conducting
      multivariable analyses in future pragmatic PBE studies. Additional studies are
      needed to test whether these results can be validated using larger groups of
      therapists, trained and not trained in MDT methods, as well as examining
      different methods to examine inter-rater agreement for identifying diverse
      interventions commonly used for managing patients during routine practice.

PMID- 22851883
TI  - Estimating the Lipophilicity of Natural Products using a Polymeric Reversed Phase
      HPLC Method.
AB  - The integration of physicochemical profiling screens such as Log P into natural
      products drug discovery programs is emerging as an approach to front-load drug
      like properties of natural product libraries for high-throughput screening. In
      this study a fast-gradient HPLC method using a polystyrene-divinylbenzene PRP-1
      column was developed to estimate the lipophilicity of marine natural products. An
      excellent correlation was found between the results of the experimental
      determined and the literature log P values for a diverse set of commercially
      available drugs using the PRP-1 column. The log P of a series of 24 marine
      natural products were evaluated using the new method and a good correlation was
      observed between the experimentally determined and software calculated log P
      values. Some discrepancies were observed between the measured value of log P and
      the software calculations of the natural products containing halogens atoms. The
      method is rapid, insensitive to impurities, and requires very little compound and
      is amenable for integration into a natural products drug discovery research
      program.

PMID- 22851884
TI  - Real-time clinical decision support system with data stream mining.
AB  - This research aims to describe a new design of data stream mining system that can
      analyze medical data stream and make real-time prediction. The motivation of the
      research is due to a growing concern of combining software technology and medical
      functions for the development of software application that can be used in medical
      field of chronic disease prognosis and diagnosis, children healthcare, diabetes
      diagnosis, and so forth. Most of the existing software technologies are case
      based data mining systems. They only can analyze finite and structured data set
      and can only work well in their early years and can hardly meet today's medical
      requirement. In this paper, we describe a clinical-support-system based data
      stream mining technology; the design has taken into account all the shortcomings
      of the existing clinical support systems.

PMID- 22851882
TI  - Proton Pump Inhibitor Therapy before and after Endoscopic Submucosal Dissection:
      A Review.
AB  - Endoscopic submucosal dissection (ESD) is a novel endoscopic procedure first
      developed in the 1990s which enables en bloc resection of gastric neoplastic
      lesions that are difficult to resect via conventional endoscopic mucosal
      resection. However, given that ESD increases the risk of intra- and post-ESD
      delayed bleeding and that platelet aggregation and coagulation in artificial
      ulcers after ESD strongly depend on intragastric pH, faster and stronger acid
      inhibition via proton pump inhibitors (PPIs) and histamine 2-receptor antagonists
      (H(2)RAs) as well as endoscopic hemostasis by thermocoagulation during ESD have
      been used to prevent ESD-related bleeding. Because PPIs more potently inhibit
      acid secretion than H(2)RAs, they are often the first-line drugs employed in ESD
      treatment. However, acid inhibition after the initial infusion of a PPI is weaker
      in the early phase than that achievable with H(2)RAs; further, PPI effectiveness
      can vary depending on genetic differences in CYP2C19. Therefore, optimal acid
      inhibition may require tailored treatment based on CYP2C19 genotype when ESD is
      performed, with a concomitant infusion of PPI and H(2)RA possibly most effective
      for patients with the rapid metabolizer CYP2C19 genotype, while PPI alone may be
      sufficient for those with the intermediate or poor metabolizer genotypes.

PMID- 22851885
TI  - Contribution of yeast and plant research for improving human health.

PMID- 22851886
TI  - Molecular imaging-guided theranostics and personalized medicine.

PMID- 22851888
TI  - Over the years, I hope I've learned a few things to pass along!

PMID- 22851889
TI  - Evergreen: A child and youth mental health framework for Canada.

PMID- 22851890
TI  - Case 2: A routine workup in a toddler with fever.

PMID- 22851887
TI  - Breast cancer chemoprevention: old and new approaches.
AB  - In 1976, Sporn has defined chemoprevention as "the use of pharmacologic or
      natural agents that inhibit the development of invasive breast cancer either by
      blocking the DNA damage that initiates carcinogenesis, or by arresting or
      reversing the progression of premalignant cells in which such damage has already
      occurred." Although the precise mechanism or mechanisms that promote a breast
      cancer are not completely established, the success of several recent clinical
      trials in preventive settings in selected high-risk populations suggests that
      chemoprevention is a rational and an appealing strategy. Breast cancer
      chemoprevention has focused heavily on endocrine intervention using selective
      estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Achieving
      much success in this particular setting and new approaches as low-dose
      administration are actually under investigations in several topics.
      Unfortunately, these drugs are active in prevention of endocrine responsive
      lesions only and have no effect in reducing the risk of estrogen-negative breast
      cancer. Thus, recently new pathways, biomarkers, and agents likely are to be
      effective in this subgroup of cancers and were put under investigation. Moreover,
      the identification of new potential molecular targets and the development of
      agents aimed at these targets within cancer have already had a significant impact
      on advanced cancer therapy and provide a wealth of opportunities for
      chemoprevention. This paper will highlight current clinical research in both ER
      positive and ER-negative breast cancer chemoprevention, explaining the biologic
      effect of the various agents on carcinogenesis and precancerous lesions, and
      finally presenting an excursus on the state-of-the-art about new molecular
      targets under investigations in breast cancer settings.

PMID- 22851891
TI  - Case 1: Headache after a European vacation.

PMID- 22851892
TI  - Communication regarding breathing support options for youth with Duchenne
      muscular dystrophy.
AB  - BACKGROUND: Ventilators for home use, manual and mechanically assisted coughing
      techniques, and the services of in-home respiratory therapists are options for
      youth with Duchenne muscular dystrophy (DMD). Evidence supports the use of these
      modalities, but there seems to be few youth who are receiving these therapies. Is
      there a knowledge transfer issue? Is there a lack of resources? What is the best
      way to discuss the issues? What do youth and parents want? OBJECTIVE: To
      determine practices, attitudes and beliefs regarding the timing and content of
      client/family communication related to ventilatory support decisions for
      individuals with DMD. METHODS: A questionnaire was sent to all 19 children's
      treatment centres in Ontario. The lead clinician responded on behalf of his or
      her centre. Another questionnaire was given to 11 families who attended a parent
      support meeting. RESULTS: Respondents from the treatment centres who provide
      services for youth with DMD indicated that there are resources in terms of
      personnel and an obligation to provide information about ventilatory support, but
      provision of information is often late and/or inconsistent. The family
      respondents wanted more information and they wanted it earlier than they are
      currently receiving it. CONCLUSIONS: Parents and youth dealing with DMD have many
      resources at their disposal in Ontario. The evidence is clear that there are long
      term health benefits to providing ventilatory support as well as instruction in
      coughing assistance. Due to the classical nature of disease progression in DMD,
      information should be provided within reasonable timelines.

PMID- 22851893
TI  - Occurrence and severity of bronchopulmonary dysplasia and respiratory distress
      syndrome after a preterm birth.
AB  - BACKGROUND: Despite notable advances in neonatal care, bronchopulmonary dysplasia
      (BPD) remains an important complication of preterm birth, frequently resulting in
      prolonged hospital stay and long-term morbidity. METHODS: A historical cohort
      study of all preterm infants (gestational age younger than 37 weeks) admitted to
      the Montreal Children's Hospital (Montreal, Quebec) between January 1, 1980, and
      December 31, 1992, was conducted. Information collected included demographic
      data, maternal and perinatal history, and main neonatal outcomes. Independent
      risk factors associated with BPD were identified by univariate analysis using one
      way ANOVA, t tests or Mantel-Haenszel chi(2) testing. Severity of disease was
      studied using an ordinal multinomial logistic regression model. RESULTS: In
      total, 1192 preterm infants were admitted, of whom 551 developed respiratory
      distress syndrome and 322 developed BPD. For each additional week of prematurity,
      the risk of developing BPD increased by 54% (adjusted OR 1.54/week [95% CI 1.45
      to 1.64]). For each point subtracted on the 1 min Apgar score, the risk of
      developing BPD was increased by 16% (OR 1.16 [95% CI 1.1 to 1.3]). BPD was also
      associated with the presence of patent ductus arteriosus (OR 3.5 [95% CI 2.1 to
      6.0]), pneumothorax in the first 48 h (OR 9.4 [95% CI 3.6 to 24.8]) or neonatal
      pneumonia/sepsis in the neonatal period (OR 1.9 [95% CI 1.1 to 3.2]). Severity of
      BPD was associated with gestational age, 1 min Apgar score, very low birth weight
      and the presence of neonatal pneumonia/sepsis. CONCLUSION: Factors associated
      with BPD following a preterm birth were the degree of prematurity, birth weight,
      Apgar score at 1 min, and the presence of patent ductus arteriosus, pneumothorax
      or neonatal pneumonia/sepsis.

PMID- 22851894
TI  - [Not Available].
AB  - OBJECTIVE: Studies targeting children born with HIV have principally focused on
      the period preceding the announcement of the diagnosis to the child. The
      objective of the present study was to explore intrafamilial communication
      dynamics following the announcement of the diagnosis. METHODOLOGY: Twenty-nine
      youths (10 to 18 years of age) living with HIV since birth participated in
      individual semistructured interviews about the following: 1) serostatus
      disclosure, 2) family relations and 3) sexual education within the family. The
      testimonials underwent a content analysis. RESULTS: The youths learned of their
      HIV-positive diagnosis at the average age of 11 years. The dynamic established
      after the announcement appears to be regulated by silence: the exchanges that
      follow mainly involve questions related to medication and prevention of sexual
      transmission of the virus. This silence preserves the familial equilibrium by
      performing three functions: protecting the mother from a feeling of guilt
      regarding transmission, assuring family harmony and feeling normal compared with
      others. The adolescent's diagnosis is generally not revealed to the extended
      family, thus preserving their integration within the family by protecting them
      from rejection, betrayal and judgement. DISCUSSION: The functions of silence and
      the secret serve as important stabilizers within the family. However, they
      contribute to the isolation of the adolescents in the form of emotional support
      that they still need. Suggestions for intervention are presented.

PMID- 22851895
TI  - Burnout among faculty physicians in an academic health science centre.
AB  - BACKGROUND: Burnout experienced by physicians is concerning because it may affect
      quality of care. OBJECTIVE: To determine the frequency of burnout among
      physicians at an academic health science centre and to test the hypothesis that
      work hours are related to burnout. METHODS: All 300 staff physicians, contacted
      through their personal e-mail, were provided an encrypted link to an anonymous
      questionnaire. The primary outcome measure, the Copenhagen Burnout Inventory, has
      three subscales: personal, work related and patient related. RESULTS: The
      response rate for the questionnaire was 70%. Quantitative demands, insecurity at
      work and job satisfaction affected all three components of burnout. Of 210 staff
      physicians, 22% (n=46) had scores indicating personal burnout, 14% (n=30) had
      scores indicating work-related burnout and 8% (n=16) had scores indicating
      patient-related burnout. The correlation between total hours worked and total
      burnout was only 0.10 (P=0.14) DISCUSSION: Up to 22% of academic paediatric
      physicians had scores consistent with mild to severe burnout. A simple reduction
      in work hours is unlikely to be successful in reducing burnout and, therefore,
      quantitative demands, job satisfaction and work insecurity may require attention
      to address burnout among academic physicians.

PMID- 22851896
TI  - Youth justice and health: An argument against proposed changes to the Youth
      Criminal Justice Act.
AB  - The Canadian Paediatric Society is deeply concerned about the negative effects on
      the developmental, psychological and emotional health of young offenders if the
      Youth Criminal Justice Act is amended as proposed. Changing Canada's youth crime
      law to achieve stiffer sentences for youth 14 years of age and older who are
      convicted of serious violent offences is contrary to the United Nations
      Convention on the Rights of the Child. Treating adolescents as adults puts them
      at serious health and human rights risks - including trauma, violence and abuse -
      and interferes with their overall development. Furthermore, rates of mental
      illness are higher among youth in custody. Youth should only serve their sentence
      in a facility that is exclusively limited to youth, and considers the rights of
      youth as well as their mental, physical, developmental and educational needs.

PMID- 22851897
TI  - Preventing varicella: Recommendations for routine two-dose varicella immunization
      in children.
AB  - All Canadian provinces and territories have had routine immunization programs for
      one-dose varicella vaccination since 2007, a strategy that has reduced varicella
      disease rates dramatically. However, breakthrough cases still occur, and some
      cases are severe. There is increasing evidence that immunity to one dose of the
      vaccine can wane in a vaccinated population, and the disease may be shifting to
      an older age group that can experience more severe disease and more
      complications. This statement presents the rationale for a two-dose immunization
      strategy in Canada, as well as recommendations for a routine two-dose varicella
      vaccine schedule for all Canadian children. Children who have received one dose
      of varicella vaccine and have not had breakthrough infection should receive
      another dose of varicella vaccine.

PMID- 22851898
TI  - Pneumonia in healthy Canadian children and youth: Practice points for management.
AB  - Although immunization has decreased the incidence of bacterial pneumonia in
      vaccinated children, pneumonia remains common in healthy children. Unless it is
      totally impractical, a chest radiograph should be performed to confirm the
      diagnosis of pneumonia. Factors such as age, vital signs and other measures of
      illness severity are critical in the decision regarding whether to admit a
      patient to hospital. Because Streptococcus pneumoniae continues to be the most
      common cause of bacterial pneumonia in children, prescribing amoxicillin or
      ampicillin for seven to 10 days remains the mainstay of empirical therapy for non
      severe pneumonia. If improvement does not occur, consideration should be given to
      searching for complications (empyema or lung abscess). Routine chest radiographs
      at the end of therapy are not recommended unless clinically indicated.

PMID- 22851899
TI  - Paediatric complicated pneumonia: Diagnosis and management of empyema.
AB  - Pneumonia can be complicated by an empyema, progressing from an exudative
      effusion, to a fibrinopurulent stage with loculations, and then organized with a
      thick fibrinous peel. The predominant causative organisms are Streptococcus
      pneumoniae, Staphyloccocus aureus (including methicillin-resistant S aureus) and
      Streptococcus pyogenes. Recently, an increased incidence of paediatric
      complicated pneumonia has been reported. For diagnostic imaging, a chest
      radiograph followed by a chest ultrasound is preferred. Computed tomography chest
      scans, with associated radiation, should not be routinely used. Antibiotic
      coverage should treat the most common causative organisms. Additional invasive or
      surgical management is recommended to reduce the duration of illness in cases not
      promptly responding to antibiotics or with significant respiratory compromise.
      Choice of management should be guided by best evidence and local expertise. Video
      assisted thorascopic surgery or insertion of a small-bore percutaneous chest tube
      with instillation of fibrinolytics are the best current options.

PMID- 22851900
TI  - Letter to the editor.

PMID- 22851901
TI  - Spurious neurological signs and symptoms in children.

PMID- 22851902
TI  - Food additives, essential nutrients and neurodevelopmental behavioural disorders
      in children: A brief review.
AB  - In recent decades, changing lifestyles in Canadian homes has led to demand for
      foods with long shelf lives that are cosmetically appealing, palatable, easy to
      prepare and to consume. Food additives, especially preservatives and artificial
      colours as well as suboptimal intake of essential nutrients, have been linked to
      hyperactive behaviours and poor attention in a subgroup of children. Although
      other risk factors (ie, genetic, etc) for these conditions have received more
      attention in the scientific literature, the authors believe that there is enough
      evidence to consider dietary influences as a modifiable risk factor. This would
      involve raising awareness among clinicians and, subsequently, reviewing food
      regulatory processes to better protect children in Canada - similar to the
      regulations recently undertaken by the British Food Standards Agency. Conflicts
      of interest due to food and medication industry support for organizations
      advocating for children would need to be resolved by open communication between
      government regulatory agencies, academia and industry. Canadian parents and
      children need to be advised to limit unnecessary food additives and consume a
      diet rich in essential nutrients while more complete relationships are being
      explored further.

PMID- 22851903
TI  - Prevalence and indications for video recording in the health care setting in
      North American and British paediatric hospitals.
AB  - BACKGROUND: Health care video recording has demonstrated value in education,
      performance assessment, quality improvement and clinical care. METHODS: A survey
      was administered to paediatric hospitals in Great Britain, Canada and the United
      States. Heads of departments or delegates from six areas (emergency departments
      [EDs], operating rooms, paediatric intensive care units [PICUs], neonatal
      intensive care units [NICUs], simulation centres and neuroepilepsy units) were
      asked 10 questions about the prevalence, indications and process issues of video
      recording. RESULTS: Seventy hospitals were surveyed, totalling 307 clinical
      areas. The hospital response rate was 100%; the rate for clinical departments was
      65%. Sixty-six hospitals (94%) currently use video recording. Video recording was
      used in 62 of 68 (91%) operating rooms; 36 of 69 (52%) PICUs; 35 of 67 (52%)
      NICUs; 12 of 65 (19%) EDs; seven of eight (88%) neuroepilepsy units and 13 of 14
      (93%) simulation centres. Education was the most common indication (112 of 204
      [55%]). Most sites obtained written consent. Since the introduction of more
      strict privacy legislation, 11 of 65 (17%) EDs have discontinued video recording.
      CONCLUSION: The present study describes video recording practices in paediatric
      hospitals in North America and Great Britain. Video recording is primarily used
      for education and most areas have a consent process.

PMID- 22851904
TI  - Topotecan and cyclophosphamide in adults with relapsed sarcoma.
AB  - Background. The combination of topotecan and cyclophosphamide (TC) has activity
      in pediatric patients with recurrent sarcoma, especially Ewing's sarcoma (EWS).
      We sought to determine the toxicity of and response to TC in adults with
      recurrent sarcoma. Patients and Methods. Adults treated with TC from 2005 to 2010
      were reviewed who received T = topotecan at 0.75 mg/m(2)/day (days 1-5) and C =
      cyclophosphamide at 250 mg/m(2)/day (days 1-5) every 21 days. Results. Fifteen
      patients, median age 31 years (range 17.5-56) had nonpleomorphic rhabdomyosarcoma
      (RMS, n = 6), EWS, n = 5, synovial sarcoma (SS, n = 2) leiomyosarcoma (LMS, n =
      1), and desmoplastic small round cell tumour (DSRCT, n = 1). Median time to
      progression was 2.5 months (range 1.6-13.0). Partial responses were seen in 2/6
      RMS and 1/2 SS. Stable disease was seen in 2/5 EWS, 1/2 SS and 1 DSRCT. The most
      common reason for stopping treatment was progressive disease 12/15, (80%).
      Hematologic toxicity was common; 7 (47%) patients required blood product
      transfusion, 5 (33%) patients had fever/neutropenia. At median follow-up time of
      7.7 months, all but 1 patient had died of disease. CONCLUSION: TC combination is
      tolerable but has only modest activity in adults with recurrent sarcoma. Other
      regimens deserve exploration for this high-risk group of patients.

PMID- 22851905
TI  - Low-grade central osteosarcoma: a difficult condition to diagnose.
AB  - Low-grade central osteosarcoma (LGCO) is a rare variant of osteosarcoma which is
      difficult to diagnose. If not treated appropriately, the tumour can recur with
      higher-grade disease. We reviewed our experience of this condition to try and
      identify factors that could improve both diagnosis and outcome. 18 patients out
      of 1540 osteosarcoma cases (over 25 years) had LGCO (1.2%). Only 11 patients
      (61%) were direct primary referrals. Almost 40% (7 of 18) cases were referred
      after treatment elsewhere when the diagnosis had not been made initially and all
      presented with local recurrence. Of the 11 who presented primarily, the first
      biopsy was diagnostic in only 6 (55%) cases. Of the remaining cases, up to three
      separate biopsies were required before a definitive diagnosis was made. Overall
      survivorship at 5 years was 90%. 17 patients were treated with limb salvage
      procedures, and one patient had an amputation. The diagnosis of LGCO remains
      challenging due to the relatively nonspecific radiological and histological
      findings. Since treatment of LGCO is so different to a benign lesion, accurate
      diagnosis is essential. Any difficult or nondiagnostic biopsies of solitary bone
      lesions should be referred to specialist tumour units for a second opinion.

PMID- 22851907
TI  - Christopher j. Salgado, m.d. And stan j. Monstrey, m.d., ph.d.

PMID- 22851908
TI  - Aesthetic and functional genital and perineal surgery: male.

PMID- 22851906
TI  - A novel inducible protein production system and neomycin resistance as selection
      marker for Methanosarcina mazei.
AB  - Methanosarcina mazei is one of the model organisms for the methanogenic order
      Methanosarcinales whose metabolism has been studied in detail. However, the
      genetic toolbox is still limited. This study was aimed at widening the scope of
      utilizable methods in this group of organisms. (i) Proteins specific to
      methanogens are oftentimes difficult to produce in E. coli. However, a protein
      production system is not available for methanogens. Here we present an inducible
      system to produce Strep-tagged proteins in Ms. mazei. The promoter p1687, which
      directs the transcription of methyl transferases that demethylate methylamines,
      was cloned into plasmid pWM321 and its activity was determined by monitoring beta
      glucuronidase production. The promoter was inactive during growth on methanol but
      was rapidly activated when trimethylamine was added to the medium. The gene
      encoding the beta-glucuronidase from E. coli was fused to a Strep-tag and was
      cloned downstream of the p1687 promoter. The protein was overproduced in Ms.
      mazei and was purified in an active form by affinity chromatography. (ii)
      Puromycin is currently the only antibiotic used as a selectable marker in Ms.
      mazei and its relatives. We established neomycin resistance as a second
      selectable marker by designing a plasmid that confers neomycin resistance in Ms.
      mazei.

PMID- 22851909
TI  - Normal penile, scrotal, and perineal anatomy with reconstructive considerations.
AB  - A broad overview is provided of the normal anatomy of the male genitalia to offer
      the best surgical outcomes in cases related to congenital abnormalities, trauma,
      cancer-related extirpation, and aesthetics. Neural and vascular anatomy is
      discussed in depth due to its critical role in maintaining function and in
      assuring tissue viability.

PMID- 22851910
TI  - Aesthetic surgery of the male genitalia.
AB  - Appearance of the male genitalia is linked with self-esteem and sexual identity.
      Aesthetic surgery of the male genitalia serves to correct perceived deficiencies
      as well as physical deformities, which may cause psychological distress.
      Attention to patient motivation for surgery and to surgical technique is key to
      achieving optimal results. In this review, the authors describe aesthetic
      surgical techniques for treatment of penile and scrotal deficiencies. They also
      discuss techniques for revision in patients with previous surgery.

PMID- 22851911
TI  - Phalloplasty in complete aphallia and ambiguous genitalia.
AB  - The most common indications for phalloplasty in children include aphallia,
      micropenis/severe penile inadequacy, ambiguous genitalia, phallic inadequacy
      associated with epispadias/bladder exstrophy and female to male gender
      reassignment in adolescents. There are many surgical options for phalloplasty;
      both local pedicled tissue as well as free tissue transfer. The advantages of
      local tissue include a more concealed donor site, less complex operation and
      potentially faster recovery. However, pedicled options are generally less
      sensate, making placement of a penile prosthesis more risky and many children
      with bladder exstrophy have been previously operated upon making the blood supply
      for local pedicled flaps less reliable. This Here the authors discuss free tissue
      transfer, including the radial forearm, the anterolateral thigh, the scapula and
      latissimus, and the fibula free flaps, as well as local rotational flaps from the
      abdomen, groin, and thigh. The goal of reconstruction should be an aesthetic and
      functional (ability to penetrate) phallus, which provides tactile and erogenous
      sensation, and the ability to urinate standing. Ideally, the operation should be
      completed in one to two operations with minimal donor site morbidity. There are
      advantages and disadvantages of each of flap and thus the choice of donor site
      should be a combination of the patient's preference and surgeon's ability to
      produce a consistent result.

PMID- 22851912
TI  - Hypospadias repair: an overview of the actual techniques.
AB  - Hypospadias is one of the most common congenital genital anomalies for which
      surgery early in life is indicated. The surgical treatment is changing
      progressively, often by repeating treatment strategies that have been used
      decades ago. Indeed, historically two-stage procedures were replaced by one-stage
      procedures and nowadays two-stage procedures gain new interest. The same for
      reconstructions using the urethral plate, which decades ago were based on the
      Thiersch Duplay principle. In the 1980s, preputial onlay flaps were most often
      used and today we see a new interest in the use of the urethral plate. The actual
      surgical approach to hypospadias is described and technical details are given.

PMID- 22851913
TI  - Scrotal and perineal reconstruction.
AB  - The scrotal and perineal area serves a special function. It is the pelvic outlet
      for the gastrointestinal tract, urinary system, and sexual function. In the male,
      the scrotum allows testicular mobility to reduce trauma and allow optimal thermal
      regulation for spermatogenesis. Trauma, infection, and cancer resection create
      defects that require reconstruction. The reconstructive goal here is to obtain
      durable coverage, function, and lastly aesthetic outcome. Pedicled local and
      regional flaps are the mainstay for this area. Due to the special function and
      appearance of the scrotum, reconstructive options for total scrotal defect always
      fall far short of the native scrotum. On the other hand, perineal reconstruction
      is overall satisfactory.

PMID- 22851914
TI  - Penile reconstruction.
AB  - A variety of surgical options exists for penile reconstruction. The key to
      success of therapy is holistic management of the patient, with attention to the
      psychological aspects of treatment. In this article, we review reconstructive
      modalities for various types of penile defects inclusive of partial and total
      defects as well as the buried penis, and also describe recent basic science
      advances, which may promise new options for penile reconstruction.

PMID- 22851915
TI  - Sex Reassignment Surgery in the Female-to-Male Transsexual.
AB  - In female-to-male transsexuals, the operative procedures are usually performed in
      different stages: first the subcutaneous mastectomy which is often combined with
      a hysterectomy-ovarectomy (endoscopically assisted). The next operative procedure
      consists of the genital transformation and includes a vaginectomy, a
      reconstruction of the horizontal part of the urethra, a scrotoplasty and a penile
      reconstruction usually with a radial forearm flap (or an alternative). After
      about one year, penile (erection) prosthesis and testicular prostheses can be
      implanted when sensation has returned to the tip of the penis. The authors
      provide a state-of-the-art overview of the different gender reassignment surgery
      procedures that can be performed in a female-to-male transsexual.

PMID- 22851916
TI  - Polyoxygenated sterols from the South China Sea soft coral Sinularia sp.
AB  - Chemical investigation of the ethanol extract of soft coral Sinularia sp.
      collected from the South China Sea led to the isolation of three new
      polyoxygenated sterols, (3S,23R,24S)-ergost-5-ene-3beta,23alpha,25-triol (1),
      (24S)-ergostane-6-acetate-3beta,5alpha,6beta,25-tetraol (2), (24S)-ergostane-6
      acetate-3beta,6beta,12beta,25-tetraol (3) together with three known ones (4-6).
      The structures, including relative configurations of the new compounds (1-3),
      were elucidated by detailed analysis of spectroscopic data (IR, UV, NMR, MS) and
      by comparison with related reported compounds. The absolute configuration of 1
      was further determined by modified Mosher's method. Compound 5 exhibited moderate
      cytotoxicity against K562 cell line with an IC(50) value of 3.18 MUM, but also
      displayed strong lethality toward the brine shrimp Artemia salina with a LC(50)
      value of 0.96 MUM.

PMID- 22851917
TI  - Three new cembranoids from the Taiwanese soft coral Sarcophyton ehrenbergi.
AB  - In order to search for new bioactive substances from marine organisms, we have
      investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi
      collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation
      of the extracts of the octocoral S. ehrenbergi led to the isolation of three new
      cembranoids, (+)-12-ethoxycarbonyl-11Z-sarcophine (1), ehrenbergol A and B (2 and
      3). The structures of these isolated metabolites were elucidated through
      extensive spectroscopic analyses. Moreover, metabolites 1-3 were evaluated in
      vitro for their cytotoxicity towards selected cancer cell lines and antiviral
      activity against human cytomegalovirus (HCMV).

PMID- 22851918
TI  - Formamido-diterpenes from the South China Sea sponge Acanthella cavernosa.
AB  - Seven new formamido-diterpenes, cavernenes A-D (1-4), kalihinenes E and F (5-6),
      and kalihipyran C (7), together with five known compounds (8-12), were isolated
      from the South China Sea sponge Acanthella cavernosa. Structures were established
      using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The
      isolated compounds were assessed for their cytotoxicity against a small panel of
      human cancer cell lines (HCT-116, A549, HeLa, QGY-7701, and MDA-MB-231) with
      IC(50) values in the range of 6-18 MUM. In addition, compound 9 showed weak
      antifungal activity against Trichophyton rubrum and Microsporum gypseum with MIC
      values of 8 and 32 MUg/mL, respectively, compound 10 displayed weak antifungal
      activity against fungi Candida albicans, Cryptococcus neoformans, T. rubrum, and
      M. gypseum with MIC values of 8, 8, 4, and 8 MUg/mL, respectively.

PMID- 22851919
TI  - The use of UV-visible reflectance spectroscopy as an objective tool to evaluate
      pearl quality.
AB  - Assessing the quality of pearls involves the use of various tools and methods,
      which are mainly visual and often quite subjective. Pearls are normally
      classified by origin and are then graded by luster, nacre thickness, surface
      quality, size, color and shape. The aim of this study was to investigate the
      capacity of Artificial Neural Networks (ANNs) to classify and estimate the
      quality of 27 different pearls from their UV-Visible spectra. Due to the opaque
      nature of pearls, spectroscopy measurements were performed using the Diffuse
      Reflectance UV-Visible spectroscopy technique. The spectra were acquired at two
      different locations on each pearl sample in order to assess surface homogeneity.
      The spectral data (inputs) were smoothed to reduce the noise, fed into ANNs and
      correlated to the pearl's quality/grading criteria (outputs). The developed ANNs
      were successful in predicting pearl type, mollusk growing species, possible
      luster and color enhancing, donor condition/type, recipient/host color, donor
      color, pearl luster, pearl color, origin. The results of this study shows that
      the developed UV-Vis spectroscopy-ANN method could be used as a more objective
      method of assessing pearl quality (grading) and may become a valuable tool for
      the pearl grading industry.

PMID- 22851921
TI  - Further insights on the carotenoid profile of the echinoderm Marthasterias
      glacialis L.
AB  - In this study, the carotenoid profile of the echinoderm Marthasterias glacialis
      L. was established using HPLC-DAD-APCI-MS/MS equipped with a C(30) column. This
      approach rendered the identification of 20 compounds, eight of them reported for
      the first time in this marine organism. Differentiation of carotenoid isomers was
      also achieved.

PMID- 22851920
TI  - Algal lectins as potential HIV microbicide candidates.
AB  - The development and use of topical microbicides potentially offers an additional
      strategy to reduce the spread of the Human Immunodeficiency Virus (HIV).
      Carbohydrate-binding agents (CBAs) that show specificity for high mannose
      carbohydrates on the surface of the heavily glycosylated envelope of HIV are
      endowed with potent anti-HIV activity. In fact, a number of algal lectins such as
      cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria
      agardhii agglutinin and griffithsin are considered as potential microbicide
      candidates to prevent the sexual transmission of HIV through topical
      applications. They not only inhibit infection of cells by cell-free virus but
      they can also efficiently prevent virus transmission from virus-infected cells to
      uninfected CD4(+) target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and
      transmission to CD4(+) T lymphocytes. This review focuses on the structural
      properties and carbohydrate specificity of these algal lectins, their antiviral
      activity against HIV and several other enveloped viruses, their safety profile
      and viral resistance patterns.

PMID- 22851923
TI  - Paralemnolide A, an unprecedented bisnorsesquiterpene from the Taiwanese soft
      coral Paralemnalia thyrsoides.
AB  - Paralemnolide A (1), possessing an unprecedented bisnorsesquiterpene skeleton,
      was isolated from the soft coral Paralemnalia thyrsoides. The structure of
      paralemnolide A was elucidated by extensive analysis of spectroscopic data. The
      anti-HCMV (human cytomegalovirus) activity of 1 and its cytotoxicity against
      selected cell lines were evaluated.

PMID- 22851922
TI  - Cyclisation increases the stability of the sea anemone peptide APETx2 but
      decreases its activity at acid-sensing ion channel 3.
AB  - APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It
      is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3)
      and it is currently in preclinical studies as a novel analgesic for the treatment
      of chronic inflammatory pain. As a peptide it faces many challenges in the drug
      development process, including the potential lack of stability often associated
      with therapeutic peptides. In this study we determined the susceptibility of wild
      type APETx2 to trypsin and pepsin and tested the applicability of backbone
      cyclisation as a strategy to improve its resistance to enzymatic degradation.
      Cyclisation with either a six-, seven- or eight-residue linker vastly improved
      the protease resistance of APETx2 but substantially decreased its potency against
      ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in
      its interaction with the channel, which we confirmed by making N- and C-terminal
      truncations. Truncation of either terminus, but especially the N-terminus, has
      detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work
      indicates that cyclisation is unlikely to be a suitable strategy for stabilising
      APETx2, unless linkers can be engineered that do not interfere with binding to
      ASIC3.

PMID- 22851924
TI  - 4-Methylenesterols from a sponge Theonella swinhoei.
AB  - Three new 4-methylenesterols, theonellasterol K (1), acetyltheonellasterol (2)
      and acetyldehydroconicasterol (3), along with two known sterols, theonellasterol
      (4) and theonellasterone (5), were isolated from the sponge Theonella swinhoei.
      The structures of these compounds were elucidated on the basis of their
      spectroscopic data and comparison of the NMR data with those of known analogues.
      Compound 1 exhibited significant cytotoxic activity against HCT-116, K562 and
      Molt 4 cancer cell lines.

PMID- 22851926
TI  - Pseudoalteromone B: a novel 15C compound from a marine bacterium
      Pseudoalteromonas sp. CGH2XX.
AB  - A novel 15C compound, pseudoalteromone B (1), possessing a novel carbon skeleton,
      was obtained from a marine bacterium Pseudoalteromonas sp. CGH2XX. This bacterium
      was originally isolated from a cultured-type octocoral Lobophytum crassum, that
      was growing in cultivating tanks equipped with a flow-through sea water system.
      The structure of 1 was established by spectroscopic methods. Pseudoalteromone B
      (1) displayed a modestly inhibitory effect on the release of elastase by human
      neutrophils.

PMID- 22851925
TI  - Atypical reactive center Kunitz-type inhibitor from the sea anemone Heteractis
      crispa.
AB  - The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea
      anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein
      sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high
      sequence identity (up to 98%) with the other known Kunitz-type sea anemones
      sequences. It was determined that the P1 Thr at the reactive site resulted in a
      decrease of the K(i) of InhVJ to trypsin and alpha-chymotrypsin (7.38 * 10(-8) M
      and 9.93 * 10(-7) M, respectively). By structure modeling the functional
      importance of amino acids at the reactive site as well as at the weak contact
      site were determined. The significant role of Glu45 for the orientation and
      stabilization of the InhVJ-trypsin complex was elucidated. We can suggest that
      there has been an adaptive evolution of the P1 residue at the inhibitor reactive
      site providing specialization or functional diversification of the paralogs. The
      appearance of a key so-called P1 Thr residue instead of Lys might lead to
      refinement of inhibitor specificity in the direction of subfamilies of serine
      proteases. The absence of Kv channel and TRPV1-receptor modulation activity was
      confirmed by electrophysiological screening tests.

PMID- 22851927
TI  - Lochmolins A-G, new sesquiterpenoids from the soft coral Sinularia lochmodes.
AB  - Seven new sesquiterpenoids, lochmolins A-G (1-7), were isolated from a Taiwanese
      soft coral Sinularia lochmodes. The structures of these metabolites were
      elucidated by extensive spectroscopic study. Compounds 1-4 were found to inhibit
      the accumulation of the LPS-induced pro-inflammatory COX-2 protein in RAW264.7
      macrophage cells.

PMID- 22851930
TI  - 100 Years after von Dungern & Hirschfeld: Kinship Investigation from Blood Groups
      to SNPs.

PMID- 22851929
TI  - Functional expression in Escherichia coli of the disulfide-rich sea anemone
      peptide APETx2, a potent blocker of acid-sensing ion channel 3.
AB  - Acid-sensing ion channels (ASICs) are proton-gated sodium channels present in the
      central and peripheral nervous system of chordates. ASIC3 is highly expressed in
      sensory neurons and plays an important role in inflammatory and ischemic pain.
      Thus, specific inhibitors of ASIC3 have the potential to be developed as novel
      analgesics. APETx2, isolated from the sea anemone Anthopleura elegantissima, is
      the most potent and selective inhibitor of ASIC3-containing channels. However,
      the mechanism of action of APETx2 and the molecular basis for its interaction
      with ASIC3 is not known. In order to assist in characterizing the ASIC3-APETx2
      interaction, we developed an efficient and cost-effective Escherichia coli
      periplasmic expression system for the production of APETx2. NMR studies on
      uniformly (13)C/(15)N-labelled APETx2 produced in E. coli showed that the
      recombinant peptide adopts the native conformation. Recombinant APETx2 is
      equipotent with synthetic APETx2 at inhibiting ASIC3 channels expressed in
      Xenopus oocytes. Using this system we mutated Phe15 to Ala, which caused a
      profound loss of APETx2's activity on ASIC3. These findings suggest that this
      expression system can be used to produce mutant versions of APETx2 in order to
      facilitate structure-activity relationship studies.

PMID- 22851928
TI  - Exploiting the nephrotoxic effects of venom from the sea anemone, Phyllodiscus
      semoni, to create a hemolytic uremic syndrome model in the rat.
AB  - In the natural world, there are many creatures with venoms that have interesting
      and varied activities. Although the sea anemone, a member of the phylum
      Coelenterata, has venom that it uses to capture and immobilise small fishes and
      shrimp and for protection from predators, most sea anemones are harmless to man.
      However, a few species are highly toxic; some have venoms containing neurotoxins,
      recently suggested as potential immune-modulators for therapeutic application in
      immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has
      multiple effects, including lethality, hemolysis and renal injuries. We
      previously reported that venom extracted from Phyllodiscus semoni induced acute
      glomerular endothelial injuries in rats resembling hemolytic uremic syndrome
      (HUS), accompanied with complement dysregulation in glomeruli and suggested that
      the model might be useful for analyses of pathology and development of
      therapeutic approaches in HUS. In this mini-review, we describe in detail the
      venom-induced acute renal injuries in rat and summarize how the venom of
      Phyllodiscus semoni could have potential as a tool for analyses of complement
      activation and therapeutic interventions in HUS.

PMID- 22851931
TI  - Genetic Kinship Investigation from Blood Groups to DNA Markers.
AB  - The forensic application of hereditary characteristics became possible after the
      discovery of human blood groups by Karl Landsteiner in 1901. The foundation for
      their use in kinship investigation was laid by Emil von Dungern and Ludwig
      Hirschfeld in 1910 by clarification of the inheritance of the ABO groups. Up to
      the middle of the 20th century further red cell membrane systems were discovered.
      From the 1920s Fritz Schiff and Georg Strassmann fought for the introduction of
      blood groups into forensic kinship investigation. A new era of hemogenetics was
      opened from 1955 as genetic polymorphisms were described in serum proteins.
      Starting in 1958 there followed the complex HLA system of white blood cells,
      which from 1963 was joined by polymophisms in erythrocyte enzymes. Therefore,
      from the 1980s, it was possible to clarify the majority of kinship cases with a
      combination of conventional markers. From 1990 to 2000 the conventional markers
      were gradually replaced by the more effective DNA markers. Simultaneously typing
      shifted from the phenotype level to the genotype level. The genomic structure of
      conventional genetic markers could also now be explained. As a reflection of
      scientific progress the legal situation also changed, particularly in the form of
      the official guidelines for kinship investigation.

PMID- 22851932
TI  - Beyond STRs: The Role of Diallelic Markers in Forensic Genetics.
AB  - Short tandem repeat (STR) polymorphisms have been firmly established as standard
      DNA marker systems since more than 15 years both in forensic stain typing as well
      as in paternity and kinship testing. However, when analyzing genetic
      relationships in deficiency cases, STRs have a couple of disadvantages due to the
      sometimes poor biostatistical efficiency as well as the possibility to observe
      one or more genetic inconsistencies that could also be explained by mutational
      events. In such situations, additional robust markers with negligible mutations
      rates such as single nucleotide polymorphisms (SNPs) and insertion/deletion
      markers (indels) can be used as adjuncts to provide decisive genetic information
      in favor for or against the assumed relationship. Both SNPs and indels can now be
      typed more easily using multiplexes of up to 50 loci based on fragment length
      analysis on instruments available in all routine forensic and paternity testing
      laboratories, thus making it possible to extend the range of markers beyond the
      currently used STRs.

PMID- 22851933
TI  - Blood Group ABO Genotyping in Paternity Testing.
AB  - BACKGROUND: The ABO blood groups result from DNA sequence variations,
      predominantly single nucleotide and insertion/deletion polymorphisms (SNPs and
      indels), in the ABO gene encoding a glycosyltransferase. The ABO blood groups
      A(1), A(2), B and O predominantly result from the wild type allele A1 and the
      major gene variants that are characterized by four diallelic markers (261G>del,
      802G>A, 803G>C, 1061C>del). Here, we were interested to evaluate the impact of
      ABO genotyping compared to ABO phenotyping in paternity testing.  METHODS: The
      major ABO alleles were determined by PCR amplification with sequence-specific
      primers (PCR-SSP) in a representative sample of 1,335 blood donors. The genotypes
      were compared to the ABO blood groups registered in the blood donor files. Then,
      the ABO phenotypes and genotypes were determined in 95 paternity trio cases that
      have been investigated by 12 short tandem repeat (STR) markers before. We
      compared statistical parameters (PL, paternity likelihood; PE, power of
      exclusion) of both blood grouping approaches.  RESULTS: The prevalence of the
      major ABO alleles and genotypes corresponded to the expected occurrence of ABO
      blood groups in a Caucasian population. The low resolution genotyping of 4
      diallelic markers revealed a correct genotype-phenotype correlation in 1,331 of
      1,335 samples (99.7%). In 60 paternity trios with confirmed paternity of the
      alleged father based on STR analysis both PL and PE of the ABO genotype was
      significantly higher than of the ABO phenotype. In 12 of 35 exclusion cases
      (34.3%) the ABO genotype also excluded the alleged father, whereas the ABO
      phenotype excluded the alleged father only in 7 cases (20%).  CONCLUSION: In
      paternity testing ABO genotyping is superior to ABO phenotyping with regard to PL
      and PE, however, ABO genotyping is not sufficient for valid paternity testing.
      Due to the much lower mutation rate compared to STR markers, blood group SNPs in
      addition to anonymous SNPs could be considered for future kinship analysis and
      genetic identity testing.

PMID- 22851934
TI  - The SNPforID Assay as a Supplementary Method in Kinship and Trace Analysis.
AB  - OBJECTIVE: Short tandem repeat (STR) analysis using commercial multiplex PCR kits
      is the method of choice for kinship testing and trace analysis. However, under
      certain circumstances (deficiency testing, mutations, minute DNA amounts), STRs
      alone may not suffice.  METHODS: We present a 50-plex single nucleotide
      polymorphism (SNP) assay based on the SNPs chosen by the SNPforID consortium as
      an additional method for paternity and for trace analysis. The new assay was
      applied to selected routine paternity and trace cases from our laboratory. 
      RESULTS AND CONCLUSIONS: Our investigation shows that the new SNP multiplex assay
      is a valuable method to supplement STR analysis, and is a powerful means to solve
      complicated genetic analyses.

PMID- 22851935
TI  - Kinship Analysis with Diallelic SNPs - Experiences with the SNPforID Multiplex in
      an ISO17025 Accreditated Laboratory.
AB  - BACKGROUND: The mutation rate of single nucleotide polymorphisms (SNPs) is
      estimated to be 100,000 times lower than that of short tandem repeats (STRs),
      which makes SNPs very suitable for relationship testing. The SNPforID multiplex
      assay was the first SNP typing assay that was a real alternative to the commonly
      used STR kits in kinship and crime case work and the first SNP assay to be
      validated in a forensic laboratory accredited according to the ISO17025 standard.
      METHODS: A total of 54 crime case samples were typed with the SNPforID multiplex
      assay. 30 samples from relationship cases were sequenced in selected SNP loci. 
      RESULTS: It was demonstrated that mixtures were easily detected with the SNPforID
      assay by analyzing the signal strengths of the detected alleles. Unusual
      imbalances in signal strengths that were observed in a few individuals could be
      explained by unexpected SNPs in one of the primer binding sites. A complicated
      relationship case with four closely related individuals is presented. 
      CONCLUSION: Mixtures can be detected with bi-allelic SNPs. The SNPforID assay is
      a very useful supplement to the STR kits in relationship testing.

PMID- 22851936
TI  - SNPs as Supplements in Simple Kinship Analysis or as Core Markers in Distant
      Pairwise Relationship Tests: When Do SNPs Add Value or Replace Well-Established
      and Powerful STR Tests?
AB  - BACKGROUND: Genetic tests for kinship testing routinely reach likelihoods that
      provide virtual proof of the claimed relationship by typing microsatellites
      commonly consisting of 12-15 standard forensic short tandem repeats (STRs).
      Single nucleotide polymorphisms (SNPs) have also been applied to kinship testing
      but these binary markers are required in greater numbers than multiple-allele
      STRs. However SNPs offer certain advantageous characteristics not found in STRs,
      including, much higher mutational stability, good performance typing highly
      degraded DNA, and the ability to be readily up-scaled to very high marker numbers
      reaching over a million loci. This article outlines kinship testing applications
      where SNPs markedly improve the genetic data obtained. In particular we explore
      the minimum number of SNPs that will be required to confirm pairwise relationship
      claims in deficient pedigrees that typify missing persons' identification or war
      grave investigations where commonly few surviving relatives are available for
      comparison and the DNA is highly degraded.  METHODS: We describe the application
      of SNPs alongside STRs when incomplete profiles or allelic instability in STRs
      create ambiguous results, we review the use of high density SNP arrays when the
      relationship claim is very distant, and we outline simulations of kinship
      analyses with STRs supplemented with SNPs in order to estimate the practical
      limit of pairwise relationships that can be differentiated from random unrelated
      pairs from the same population.  RESULTS: The minimum number of SNPs for robust
      statistical inference of parent-offspring relationships through to those of
      second cousins (S-3-3) is estimated for both simple, single multiplex SNP sets
      and for subsets of million-SNP arrays.  CONCLUSIONS: There is considerable scope
      for resolving ambiguous STR results and for improving the statistical power of
      kinship analysis by adding small-scale SNP sets but where the pedigree is
      deficient the pairwise relationships must be relatively close. For more distant
      relationships it is possible to reduce chip-based SNP arrays from the million+
      markers down to ~7,000. However, such numbers indicate that current genotyping
      approaches will not be able to deliver sufficient data to resolve distant
      pairwise relationships from the limited DNA typical of the most challenging
      identification cases.

PMID- 22851937
TI  - Automated Genotyping of a Highly Informative Panel of 40 Short Insertion-Deletion
      Polymorphisms Resolved in Polyacrylamide Gels for Forensic Identification and
      Kinship Analysis.
AB  - OBJECTIVE: Short insertion-deletion polymorphisms (indels) are the second most
      abundant form of genetic variations in humans after SNPs. Since indel alleles
      differ in size, they can be typed using the same methodological approaches and
      equipment currently utilized for microsatellite genotyping, which is already
      operational in forensic laboratories. We have previously shown that a panel of 40
      carefully chosen indels has excellent potential for forensic identification, with
      combined probability of identity (match probability) of 7.09 * 10(-17) for
      Europeans.  METHODS: We describe the successful development of a multiplex system
      for genotyping the 40-indel panel in long thin denaturing polyacrylamide gels
      with silver staining. We also demonstrate that the system can be easily fully
      automated with a simple large scanner and commercial software.  RESULTS AND
      CONCLUSION: The great advantage of the new system of typing is its very low cost.
      The total price for laboratory equipment is less than EUR 10,000.-, and
      genotyping of an individual patient will cost less than EUR 10.- in supplies.
      Thus, the 40-indel panel described here and the newly developed 'low-tech'
      analysis platform represent useful new tools for forensic identification and
      kinship analysis in laboratories with limited budgets, especially in developing
      countries.

PMID- 22851938
TI  - Influence of Intravenous Immunoglobulin Treatment on Thrombopoiesis.
AB  - AIM: The mechanisms by which intravenous immunoglobulins (IVIg) result in an
      increase in platelet counts in most patients with autoimmune thrombocytopenia
      (ITP) have not yet been fully explained. One of these mechanisms may be related
      to stimulation of thrombopoiesis.  METHODS: A total of 13 adult patients who
      received IVIg were studied: 11 patients with primary ITP, 1 patient with ITP
      related to common variable immunodeficiency (CVID), and 1 patient with
      uncharacterized thrombocytopenia. IVIg (0.5-1.5 g/kg body weight) was
      administered on consecutive days (days 1-3). Endogenous thrombopoietin (eTPO) was
      measured prior to and at least 1 day following treatment. In addition, IL-6 was
      measured in 5 of the treated patients.  RESULTS: In 10 of 13 patients, IVIg
      treatment resulted in an increase in platelet counts. eTPO remained unchanged or
      elevated in almost all cases where the platelet count remained low (<100 *
      10(3)/MU0. In all cases with normal or increased platelet counts (>100 *
      10(3)/MU0, the eTPO concentration decreased. Furthermore, IVIg induced IL-6
      synthesis in all 5 examined patients.  CONCLUSION: Our data indicate that the
      induction of eTPO synthesis by IL-6 may be a potential mechanism in which IVIg
      may stimulate thrombopoiesis. Further studies are required to characterize this
      mechanism.

PMID- 22851939
TI  - Erythropoietin May Improve Anemia in Patients with Autoimmune Hemolytic Anemia
      Associated with Reticulocytopenia.
AB  - BACKGROUND: Management of patients with autoimmune hemolytic anemia (AIHA) and
      reticulocytopenia remains challenging.  CASE REPORTS: Two patients with
      decompensated AIHA who were receiving immunosuppressive drugs were treated with
      erythropoietin (EPO). Administration of EPO increased reticulocyte counts and
      hemoglobin concentrations in both cases. One patient completely recovered
      following a short course of treatment. Hemolysis could be compensated in the
      second patient using only mild doses of immunosuppressive drugs in combination
      with EPO.  CONCLUSION: The administration of EPO should be considered in patients
      with therapy-refractory AIHA, particularly in the presence of reticulocytopenia.

PMID- 22851940
TI  - Incident and emergency medical services management from a regional perspective.
AB  - Traffic crashes and other emergencies have impacts on traffic operations in
      transportation networks, often resulting in non-recurring congestion. Congestion,
      in turn, may impede the ability of Emergency Medical Services (EMS) to provide
      timely response to those in need of medical attention. The work in this paper
      investigated the impact of incidents of varying severity and duration on
      transportation network performance in the Birmingham (AL, USA) area. The
      intensity and extent of the impact over space and time were assessed on the basis
      of average speeds. The analysis of incident scenarios was performed using the
      Visual Interactive System for Transport Algorithms (VISTA) platform. Moreover,
      first responders' travel times to the scene of the incident were collected to
      identify best units for responding, in an effort to improve current dispatching
      practices. Finally, a secondary incident on the EMS to the hospital was
      considered to further demonstrate the superiority of Dynamic Traffic Assignment
      (DTA) over traditional static assignment methods in capturing dynamically
      changing traffic conditions. The study findings are expected to benefit local
      transportation planners, traffic engineers, emergency responders, and policy
      makers by allowing them to assess various response strategies to major incidents
      and emergencies and select the ones that minimize their potential impacts.

PMID- 22851941
TI  - Symptomatological features of patients with and without Ecstasy use during their
      first psychotic episode.
AB  - BACKGROUND: Ecstasy use is generally chosen by adolescents and young adults for
      its entactogenic properties (the production of feelings of empathy, love, and
      emotional closeness to others.) Despite this desired and frequently realized
      outcome, Ecstasy use has often resulted in the genesis of psychotic symptoms and
      aggressive behaviors, particularly after chronic and/or intensive use. METHODS:
      To explore the negative consequences of Ecstasy use and to examine the aggressive
      nature oftentimes seen in many Ecstasy users we employed a case-control study
      model. We compared, by means of validated psychometric tests, the
      psychopathological symptoms (BPRS), the aggressiveness (OAS) and the social
      adjustment (DSM-GAF) of psychotic patients with (n = 23) and without (n = 46)
      recent user of Ecstasy, during their first psychotic episode and hospitalization.
      All 23 Ecstasy users were Ecstasy users only. RESULTS: Almost all of the
      psychotic symptoms were of similar severity in both groups. Blunted affect was
      milder in users than in non-users, whereas hostility and aggressive behavior was
      significantly more severe in users than in non-users. CONCLUSIONS: psychosis with
      a high level of aggressiveness and violence constitutes an important 'side
      effect' that surely runs counter to the expected entactogenic action of Ecstasy.
      At a patient psycho-educational level, this study suggests that the use of
      Ecstasy may be counterproductive with respect to user expectations.

PMID- 22851942
TI  - Perspectives of community- and faith-based organizations about partnering with
      local health departments for disasters.
AB  - Public health emergency planners can better perform their mission if they develop
      and maintain effective relationships with community- and faith-based
      organizations in their jurisdictions. This qualitative study presents six themes
      that emerged from 20 key informant interviews representing a wide range of
      American community- and faith-based organizations across different types of
      jurisdictions, organizational types, and missions. This research seeks to provide
      local health department public health emergency planners with tools to assess and
      improve their inter-organizational community relationships. The themes identified
      address the importance of community engagement, leadership, intergroup dynamics
      and communication, and resources. Community- and faith-based organizations
      perceive that they are underutilized or untapped resources with respect to public
      health emergencies and disasters. One key reason for this is that many public
      health departments limit their engagement with community- and faith-based
      organizations to a one-way "push" model for information dissemination, rather
      than engaging them in other ways or improving their capacity. Beyond a
      reprioritization of staff time, few other resources would be required. From the
      perspective of community- and faith-based organizations, the quality of
      relationships seems to matter more than discrete resources provided by such ties.

PMID- 22851943
TI  - Effects of cold air on cardiovascular disease risk factors in rat.
AB  - The purpose of this study is to explore possible potential implications of cold
      air in cardiovascular disease (CVD) risk in rats. Healthy Wistar rats were
      exposed to artificial cold air under laboratory conditions, and their systolic
      blood pressure, heart rate, vasoconstriction, CVD risk factors, and myocardial
      damage indicators after cold air exposure were determined and evaluated. Systolic
      blood pressure, whole blood viscosity, and plasma level of norepinephrine,
      angiotensinII, low density lipoprotein, total cholesterol, and fibrinogen in
      treatment groups increased significantly compared with control groups. No
      significant variations were found in plasma Mb and cTnT and myocardial tissue
      between the treatment and control groups. Results indicate that: (1) higher
      levels of SBP, WBV and LDL/HDL, total cholesterol (TC), and FG in blood may
      indicate higher CVD risks during cold air exposure; (2) cold air may exert
      continuous impacts on SBP and other CVD risk factors.

PMID- 22851944
TI  - Effects of delta-aminolevulinic acid dehydratase polymorphisms on susceptibility
      to lead in Han subjects from southwestern China.
AB  - This study is to determine the distribution of the delta-aminolevulinic acid
      dehydratase (ALAD) polymorphism among Han subjects of the Chinese population and
      to study whether the polymorphism in the ALAD gene modifies the toxicity of lead
      in lead-exposed workers. For this purpose we conducted a cross-sectional study on
      156 Chinese workers who were exposed to lead in lead-acid battery and electric
      flex manufacturing plants. The authors found that the allele frequencies of ALAD1
      and ALAD2 were 0.9679 and 0.0321, respectively. Workers with the ALAD 1-1
      genotype were associated with higher blood lead levels than those with the ALAD 1
      2 genotype. Blood and urine lead levels were much higher in storage battery
      workers than in cable workers. The self-conscious symptom survey showed that the
      incidences of debilitation, amnesia and dreaminess were much higher in those had
      more than five years of tenure or contact with lead on the job within the ALAD 1
      1 genotype subgroup. Laboratory examinations showed that serum iron and zinc
      levels in workers' with the ALAD 1-2 genotype were higher than those with the
      ALAD 1-1 genotype, especially in storage-battery workers. Correlation analysis
      indicated that the blood lead level negatively correlated with serum calcium,
      iron and zinc level. The data of this study suggest that the ALAD gene
      polymorphism and serum ion levels may modify the kinetics of lead in blood.
      Therefore, the authors recommend that an adequate intake of dietary calcium,
      iron, and zinc or the calcium, iron, and zinc supplementation should be
      prescribed to Chinese lead exposed workers.

PMID- 22851945
TI  - Comment on the "Ground water chemistry changes before major earthquakes and
      possible effects on animals", by R. A. Grant, T. Halliday, W. P. Balderer, F.
      Leuenberger, M. Newcomer, G. Cyr and F. T. Freund. Int. J. Environ. Res. Public
      Health, 2011, 8, 1936-1956.
AB  - Here, we suggest that electromagnetic emissions before rupture may be the
      mechanism for the explanation of abnormal behavior of animals before earthquakes.

PMID- 22851946
TI  - Reply to "Comment on the 'Ground water chemistry changes before major earthquakes
      and possible effects on animals', by R. A. Grant, T. Halliday, W. P. Balderer, F.
      Leuenberger, M. Newcomer, G. Cyr and F. T. Freund. Int. J. Environ. Res. Public
      Health, 2011, 8, 1936-1956" from Friedemann Freund, Rachel Grant and Co-Authors.

PMID- 22851947
TI  - A cluster randomized trial to evaluate a health education programme "Living with
      Sun at School".
AB  - Over-exposure to sunlight increases the risk of skin cancers, particularly when
      exposure occurs during childhood. School teachers can play an active role in
      providing an education programme that can help prevent this. "Living with the
      Sun," (LWS) is a sun safety education program for school children based on a
      handy guide for classroom activities designed to improve children's knowledge,
      but moreover to positively modify their sun safety attitudes and behaviours. The
      goal of our study was to determine the effectiveness of this programme by
      examining children's knowledge, attitude and sun exposure behaviours prior to and
      after the completion of the programme. We carried out a cluster randomised trial
      in which the classes were randomly assigned to one of two groups; one using the
      LWS programme and another that didn't, serving as the control. Data was collected
      before completion of the programme and an additional three times in the year
      after completion. The 70 participating classes (1,365 schoolchildren) were
      distributed throughout France. Statistical analysis confirmed that knowledge of
      sun risk increased significantly in the LWS classes (p < 0.001). Both groups
      positively changed their attitudes when considering the best sun protection, but
      the LWS group proved to consistently be more convinced (p = 0.04). After the
      summer holidays, differences between the two groups decreased throughout the year
      but stayed globally significant. We also observed some significant behaviour
      modification during the holidays. For instance, the LWS group applied sunscreen
      more frequently than the control group, and were more likely to wear a hat (72%
      versus 59%) and use a sun umbrella on the beach (75% versus 64%).

PMID- 22851948
TI  - Risk perception and occupational accidents: a study of gas station workers in
      southern Brazil.
AB  - The present study aimed to identify the perceptions of gas station workers about
      physical, chemical, biological and physiological risk factors to which they are
      exposed in their work environment; identify types of occupational accidents
      involving gas station workers and; report the development of a socioenvironmental
      intervention as a tool for risk communication to gas station workers. A
      quantitative study was performed with 221 gas station workers in southern Brazil
      between October and December 2010. Data collection was performed between October
      to December 2010 via structured interviews. The data were analyzed using SPSS
      19.0. The participants identified the following risk types: chemical (93.7%),
      physical (88.2%), physiological (64.3%) and biological (62.4%). In this sample,
      94.1% of gas station workers reported occupational accidents, and 74.2% reported
      fuel contact with the eyes (p < 0.05). It is concluded that workers perceive
      risks, and that they tend to relate risks with the occurrence of occupational
      accidents as an indicator of the dangerous nature of their work environment.

PMID- 22851949
TI  - Assessment of knowledge, behaviour and sun protection practices among health
      services vocational school students.
AB  - There has been a significant increase in the cases of skin cancer throughout the
      world in the last few decades. Although the mortality rate of skin cancer is
      relatively low, its impact on other health aspects is high and the treatment of
      undesired aesthetic damage is costly. According to disability-adjusted life year
      rates (DALY), 1.5 million days are estimated to be lost from people's lives every
      year worldwide due to ultraviolet (UV) radiation. The purpose of this study was
      to raise sun health awareness levels among health services vocational school
      students. A total of 414 students were included in the analysis. A questionnaire
      form was used to evaluate knowledge, attitudes and behaviours among the survey
      sample. The average level of knowledge concerning the effects of the sun was
      found to be 8.64 +/- 2.5 out of 15 points. All socio-demographic factors were
      analysed, but the only significant variables found were age and the possible
      presence of skin cancer within the immediate family (p < 0.05).

PMID- 22851950
TI  - Vitamin D beliefs and associations with sunburns, sun exposure, and sun
      protection.
AB  - The main objective of this study was to examine certain beliefs about vitamin D
      and associations with sun exposure, sun protection behaviors, and sunburns. A
      total of 3,922 lifeguards, pool managers, and parents completed a survey in 2006
      about beliefs regarding vitamin D and sun-related behaviors. Multivariate ordinal
      regression analyses and linear regression analysis were used to examine
      associations of beliefs and other variables. Results revealed that Non-Caucasian
      lifeguards and pool managers were less likely to agree that they needed to go out
      in the sun to get enough vitamin D. Lifeguards and parents who were non-Caucasian
      were less likely to report that sunlight helped the body to produce vitamin D. A
      stronger belief about the need to go out in the sun to get enough vitamin D
      predicted more sun exposure for lifeguards. For parents, a stronger belief that
      they can get enough vitamin D from foods predicted greater sun protection and a
      stronger belief that sunlight helps the body produce vitamin D predicted lower
      sun exposure. This study provides information regarding vitamin D beliefs and
      their association with certain sun related behaviors across different demographic
      groups that can inform education efforts about vitamin D and sun protection.

PMID- 22851951
TI  - First report of a toxic Nodularia spumigena (Nostocales/ Cyanobacteria) bloom in
      sub-tropical Australia. I. Phycological and public health investigations.
AB  - Cyanobacterial blooms represent one of the most conspicuous and widespread
      waterborne microbial hazards to human and ecosystem health. Investigation of a
      cyanobacterial bloom in a shallow brackish water recreational cable ski lake in
      south-eastern Queensland, Australia revealed the dominance of the toxigenic
      species Nodularia spumigena. The bloom spanned three months, during which time
      cell concentrations exceeded human guideline thresholds for recreational risk,
      and concentrations of the hepatotoxic cyanotoxin nodularin exceeded 200 ug L(-1).
      Cyanotoxin origin and identification was confirmed by amplification of the ndaF
      specific PCR product and sequencing of the 16S rRNA gene. From the limited data
      available leading up to, and throughout the bloom, it was not possible to
      establish the set of causative factors responsible for its occurrence. However a
      combination of factors including salinity, hydraulic retention time and nutrient
      status associated with an extended period of drought are likely to have
      contributed. This was the first known occurrence of this species in bloom
      proportions from sub-tropical Australia and as such represents a hitherto
      uncharacterized risk to human and ecosystem health. It highlights the need for
      adaptive monitoring regimes to ensure a comprehensive understanding of the
      potentially toxic cyanobacteria likely to inhabit any given region. Such
      monitoring needs to recognize that cyanobacteria have a significant capacity for
      range expansion that has been facilitated by recent changes in global climate.

PMID- 22851952
TI  - First report of a toxic Nodularia spumigena (Nostocales/ Cyanobacteria) bloom in
      sub-tropical Australia. II. Bioaccumulation of nodularin in isolated populations
      of mullet (Mugilidae).
AB  - Fish collected after a mass mortality at an artificial lake in south-east
      Queensland, Australia, were examined for the presence of nodularin as the lake
      had earlier been affected by a Nodularia bloom. Methanol extracts of muscle,
      liver, peritoneal and stomach contents were analysed by HPLC and tandem mass
      spectrometry; histological examination was conducted on livers from captured
      mullet. Livers of sea mullet (Mugil cephalus) involved in the fish kill contained
      high concentrations of nodularin (median 43.6 mg/kg, range 40.8-47.8 mg/kg dry
      weight; n = 3) and the toxin was also present in muscle tissue (median 44.0
      MUg/kg, range 32.3-56.8 MUg/kg dry weight). Livers of fish occupying higher
      trophic levels accumulated much lower concentrations. Mullet captured from the
      lake 10 months later were also found to have high hepatic nodularin levels. DNA
      sequencing of mullet specimens revealed two species inhabiting the study lake: M.
      cephalus and an unidentified mugilid. The two mullet species appear to differ in
      their exposure and/or uptake of nodularin, with M. cephalus demonstrating higher
      tissue concentrations. The feeding ecology of mullet would appear to explain the
      unusual capacity of these fish to concentrate nodularin in their livers; these
      findings may have public health implications for mullet fisheries and aquaculture
      production where toxic cyanobacteria blooms affect source waters. This report
      incorporates a systematic review of the literature on nodularin measured in
      edible fish, shellfish and crustaceans.

PMID- 22851953
TI  - Secondary leukemia associated with the anti-cancer agent, etoposide, a
      topoisomerase II inhibitor.
AB  - Etoposide is an anticancer agent, which is successfully and extensively used in
      treatments for various types of cancers in children and adults. However, due to
      the increases in survival and overall cure rate of cancer patients, interest has
      arisen on the potential risk of this agent for therapy-related secondary
      leukemia. Topoisomerase II inhibitors, including etoposide and teniposide,
      frequently cause rearrangements involving the mixed lineage leukemia (MLL) gene
      on chromosome 11q23, which is associated with secondary leukemia. The prognosis
      is extremely poor for leukemias associated with rearrangements in the MLL gene,
      including etoposide-related secondary leukemias. It is of great importance to
      gain precise knowledge of the clinical aspects of these diseases and the
      mechanism underlying the leukemogenesis induced by this agent to ensure correct
      assessments of current and future therapy strategies. Here, I will review current
      knowledge regarding the clinical aspects of etoposide-related secondary leukemia,
      some probable mechanisms, and strategies for treating etoposide-induced leukemia.

PMID- 22851954
TI  - Physical activity associated with public transport use--a review and modelling of
      potential benefits.
AB  - Active travel, particularly walking and cycling, has been recommended because of
      the health benefits associated with increased physical activity. Use of public
      transport generally involves some walking to bus stops or train stations. This
      paper is a systematic review of how much time is spent in physical activity among
      adults using public transport. It also explores the potential effect on the
      population level of physical activity if inactive adults in NSW, Australia,
      increased their walking through increased use of public transport. Of 1,733
      articles, 27 met the search criteria, and nine reported on absolute measures of
      physical activity associated with public transport. A further 18 papers reported
      on factors associated with physical activity as part of public transport use. A
      range of 8-33 additional minutes of walking was identified from this systematic
      search as being attributable to public transport use. Using "bootstrapping"
      statistical modelling, if 20% of all inactive adults increased their walking by
      only 16 minutes a day for five days a week, we predict there would be a
      substantial 6.97% increase in the proportion of the adult population considered
      "sufficiently active". More minutes walked per day, or a greater uptake of public
      transport by inactive adults would likely lead to significantly greater increases
      in the adult population considered sufficiently active.

PMID- 22851955
TI  - Using bioinformatic approaches to identify pathways targeted by human
      leukemogens.
AB  - We have applied bioinformatic approaches to identify pathways common to chemical
      leukemogens and to determine whether leukemogens could be distinguished from non
      leukemogenic carcinogens. From all known and probable carcinogens classified by
      IARC and NTP, we identified 35 carcinogens that were associated with leukemia
      risk in human studies and 16 non-leukemogenic carcinogens. Using data on
      gene/protein targets available in the Comparative Toxicogenomics Database (CTD)
      for 29 of the leukemogens and 11 of the non-leukemogenic carcinogens, we analyzed
      for enrichment of all 250 human biochemical pathways in the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) database. The top pathways targeted by the leukemogens
      included metabolism of xenobiotics by cytochrome P450, glutathione metabolism,
      neurotrophin signaling pathway, apoptosis, MAPK signaling, Toll-like receptor
      signaling and various cancer pathways. The 29 leukemogens formed 18 distinct
      clusters comprising 1 to 3 chemicals that did not correlate with known mechanism
      of action or with structural similarity as determined by 2D Tanimoto coefficients
      in the PubChem database. Unsupervised clustering and one-class support vector
      machines, based on the pathway data, were unable to distinguish the 29
      leukemogens from 11 non-leukemogenic known and probable IARC carcinogens.
      However, using two-class random forests to estimate leukemogen and non-leukemogen
      patterns, we estimated a 76% chance of distinguishing a random leukemogen/non
      leukemogen pair from each other.

PMID- 22851956
TI  - Suicide among war veterans.
AB  - Studies aiming to identify if war veterans are at higher risk of suicide have
      often produced inconsistent results; this could be due to the complexity of
      comparisons and different methodological approaches. It should be noted that this
      contingent has many risk factors, such as stressful exposures, wounds, brain
      trauma and pain syndrome. Most recent observations confirm that veterans are
      really more likely to die of suicide as compared to the general population; they
      are also more likely to experience suicidal ideation and suffer from mental
      health problems. Suicides are more frequent in those who develop PTSD, depression
      and comorbid states due to war exposure. Combat stress and its' frequency may be
      an important factor leading to suicide within the frame of the stress
      vulnerability model. According to this model, the effects of stress may interact
      with social factors, interpersonal relations and psychological variables
      producing suicidal tendencies. Modern understanding of stress-vulnerability
      mechanisms based on genetic predispositions, early life development, level of
      exposure to stress and stress-reactivity together with interpersonal aspects may
      help to build more effective suicide prevention programs based on
      universal/selective/indicated prevention principles.

PMID- 22851957
TI  - Global Adult Tobacco Survey data as a tool to monitor the WHO Framework
      Convention on Tobacco Control (WHO FCTC) implementation: the Brazilian case.
AB  - The Global Adult Tobacco Survey (GATS) was conducted in Brazil to provide data on
      tobacco use in order to monitor the WHO FCTC implementation in the country. It
      was carried out in 2008 using an international standardized methodology. The
      instrument included questions about tobacco use prevalence, cessation, secondhand
      smoke, knowledge, attitudes, media and advertising. Weighted analysis was used to
      obtain estimates. A total of 39,425 interviews were conducted. The prevalence of
      current tobacco use was 17.5%, (22.0%, men; 13.3%, women). The majority of users
      were smokers (17.2%) and their percentage was higher in rural areas (20.4%) than
      in urban areas (16.6%). About 20% of individuals reported having been exposed to
      tobacco smoke in public places. Over 70% of respondents said they had noticed
      anti-smoking information in several media and around 65% of smokers said they had
      considered quitting because of warning labels. About 30% of respondents had
      noticed cigarette advertising at selling points and 96% recognized tobacco use as
      a risk factor for serious diseases. Data in this report can be used as baseline
      for evaluation of new tobacco control approaches in Brazil, vis-a-vis WHO FCTC
      demand reduction measures.

PMID- 22851958
TI  - Commensal Pseudomonas species isolated from wastewater and freshwater milieus in
      the Eastern Cape Province, South Africa, as reservoir of antibiotic resistant
      determinants.
AB  - Pseudomonas species are opportunistic pathogens with implications in a wide range
      of diseases including cystic fibrosis and sickle cell anaemia. Because of their
      status as multidrug resistant (MDR) and extremely drug resistant (XDR) bacteria
      Pseudomonas species represent a threat to public health. Prevalence, antibiogram
      and associated antibiotic resistant genes of Pseudomonas species isolated from
      freshwater and mixed liquor environments in the Eastern Cape Province of South
      Africa were assessed. Polymerase chain reaction (PCR) based technique was used to
      identify the isolates and screen for antibiotic resistant genes. The result shows
      occurrence of Pseudomonas spp. in freshwater and mixed liquor as follows: 71.42%
      and 37.5% (P. putida), 14.28% and 31.25% (P. fluorescens), 7.14% and 6.25% (P.
      aeruginosa) and 7.14% and 25% for other Pseudomonas species respectively. Disk
      diffusion antibiogram of the Pseudomonas isolates from the two locations showed
      100% resistance to penicillin, oxacillin, clindamycin, rifampicin and 100%
      susceptibility to ciprofloxacin and gentamicin with varied percentage resistances
      to cephalothin, nalidixic acid, tetracycline, and ampicillin. The bla(TEM)
      antibiotic resistant gene was detected in 12.5% of P. putida, 57.14% of P.
      fluorescens, 100% P. aeruginosa and 40% in other Pseudomonas species. Similarly,
      Integrons conserved segment were detected in 12.5% of P. putida, 57.14% of P.
      fluorescens, 100% of P. aeruginosa and 40% of other Pseudomonas species. The
      presence of bla(TEM) gene and integrons conserved segment in some of the isolates
      is worrisome and suggest Pseudomonas species as important reservoirs of multidrug
      resistance genes in the Eastern Cape Province environment.

PMID- 22851959
TI  - Smoking health professional student: an attitudinal challenge for health
      promotion?
AB  - Tobacco is a major preventable cause of premature morbidity and mortality. Health
      professionals are uniquely positioned to provide targeted interventions and
      should be empowered to provide cessation counselling that influence patient
      smoking. A cross-sectional national survey was administered to all third year
      students in four disciplines at the University of Malta. The Global Health
      Professional Student Survey (GHPSS) questionnaire was distributed to collect
      standardised demographic, smoking prevalence, behavioural, and attitudinal data.
      81.9% completed the questionnaire (n = 173/211). A positive significant
      association between tobacco smoke exposure at home and current smoking status was
      identified. Non-smokers regarded anti-tobacco policies more favourably than
      smokers, being more likely to agree with banning of tobacco sales to adolescents
      (OR 3.6; 95% CI: 2.5-5.3; p <= 0.001); and with a smoking ban in all public
      places (OR 8.9; 95% CI: 6.1-13.1; p <= 0.001). Non-smokers favoured a role for
      health professionals in promoting smoking cessation (OR 5.1; 95% CI: 3.1-8.5; p
      <= 0.001). Knowledge of antidepressants as tools for smoking cessation was also
      associated with a perceived role for skilled health professionals in cessation
      counselling (OR 4.9; 95% CI: 1.8-13.3; p = 0.002). Smoking negatively influences
      beliefs and attitudes of students toward tobacco control. There is a need to
      adopt a standard undergraduate curriculum containing comprehensive tobacco
      prevention and cessation training to improve their effectiveness as role models.

PMID- 22851960
TI  - Chronic Inflammation and Coronary Atherosclerosis in Patients with End-Stage
      Renal Disease.
AB  - The key role of chronic inflammation in the pathogenesis of atherosclerosis has
      become increasingly apparent in recent years based on the results of
      experimental, epidemiologic and clinical studies. Coronary artery disease and its
      complications occur with disproportionately high frequency in patients with end
      stage renal disease (ESRD) and contribute substantially to cardiovascular
      morbidity and mortality in this population. Traditional cardiovascular risk
      factors occur commonly in patients with ESRD. In addition, a variety of patient
      related and dialysis-related factors unique to ESRD predispose to chronic
      inflammation and by doing so are thought to contribute to coronary
      atherosclerosis and its complications. These risk factors may serve as
      therapeutic targets and as such may offer the potential for altering the natural
      history of coronary atherosclerosis in ESRD.

PMID- 22851961
TI  - Myocardial Stunning with Hemodialysis: Clinical Challenges of the Cardiorenal
      Patient.
AB  - We discuss the current state of knowledge related to the pathogenesis of
      myocardial stunning as well as the potential mechanisms responsible for the
      clinical presentation of myocardial stunning in hemodialysis patients. We suggest
      future research areas for this critical and clinically important condition in
      this high-risk patient population. In consideration of acute and chronic changes
      secondary to dialysis, especially in patients with risk for coronary artery
      disease, the prevalence of myocardial stunning and its role in the natural
      history of these patients' disease progression is considered. We propose a
      paradigm: that the majority of the pathophysiologic mechanisms by which
      hemodialysis may induce myocardial stunning falls into two categories with (1)
      vascular and/or (2) metabolic contributions. In order to prevent eventual
      myocardial hibernation, myocardial remodeling, scarring, and loss of contractile
      function with aberrant electrical conductivity that could lead to sudden death,
      it is imperative to identify the risk factors associated with myocardial stunning
      during hemodialysis. Further understanding of these mechanisms may lead to novel
      clinical interventions and pharmacologic therapeutic agents.

PMID- 22851962
TI  - Gestational Diabetes and the Offspring: Implications in the Development of the
      Cardiorenal Metabolic Syndrome in Offspring.
AB  - The risk of developing type 2 diabetes and cardiovascular disease in women who
      had previously been diagnosed with gestational diabetes (GDM) is well
      established. There is increasing evidence that the offspring of women with GDM
      are at increased risk for the development of all components of the cardiorenal
      metabolic syndrome. Overall, it appears that these offspring have an increased
      risk for overweight/obesity, insulin resistance, higher blood pressure, renal
      disease, and type 2 diabetes. However, distinct differences in regional
      populations, lack of routine screening and treatment of GDM worldwide, and long
      follow-up periods for offspring represent a challenge in assessing the risk for
      development of these abnormalities in the offspring of women who have had GDM.

PMID- 22851964
TI  - PPARgamma Expression and Function in Mycobacterial Infection: Roles in Lipid
      Metabolism, Immunity, and Bacterial Killing.
AB  - Tuberculosis continues to be a global health threat, with drug resistance and HIV
      coinfection presenting challenges for its control. Mycobacterium tuberculosis,
      the etiological agent of tuberculosis, is a highly adapted pathogen that has
      evolved different strategies to subvert the immune and metabolic responses of
      host cells. Although the significance of peroxisome proliferator-activated
      receptor gamma (PPARgamma) activation by mycobacteria is not fully understood,
      recent findings are beginning to uncover a critical role for PPARgamma during
      mycobacterial infection. Here, we will review the molecular mechanisms that
      regulate PPARgamma expression and function during mycobacterial infection.
      Current evidence indicates that mycobacterial infection causes a time-dependent
      increase in PPARgamma expression through mechanisms that involve pattern
      recognition receptor activation. Mycobacterial triggered increased PPARgamma
      expression and activation lead to increased lipid droplet formation and
      downmodulation of macrophage response, suggesting that PPARgamma expression might
      aid the mycobacteria in circumventing the host response acting as an escape
      mechanism. Indeed, inhibition of PPARgamma enhances mycobacterial killing
      capacity of macrophages, suggesting a role of PPARgamma in favoring the
      establishment of chronic infection. Collectively, PPARgamma is emerging as a
      regulator of tuberculosis pathogenesis and an attractive target for the
      development of adjunctive tuberculosis therapies.

PMID- 22851963
TI  - Obesity, Diabetes, the Cardiorenal Syndrome, and Risk for Cancer.
AB  - Numerous epidemiological studies confirm that the prevalence of obesity and the
      cardiorenal metabolic syndrome (CRS) is extraordinarily high and that the rates
      have increased dramatically in the last three decades. In addition,
      epidemiological data demonstrate that obesity, the CRS, and diabetes are
      inextricably linked and are all associated with an increased incidence of a
      number of solid tissue cancers. The mechanisms for this association have been
      examined, including, but not limited to, higher levels of insulin and free levels
      of insulin-like growth factor and insulin resistance in obesity and the CRS.
      Mortality, morbidity, and the associated health care costs which are the link
      between obesity, the CRS, and diabetes are just beginning to be examined. In
      addition, we review the advantages of implementing lifestyle and surgical changes
      to modify obesity, lessening the development of the CRS, diabetes, and associated
      cancers. Epidemiological data regarding the general mechanisms of the
      pathogenesis of cancers associated with obesity, the CRS, and diabetes
      (specifically colon, pancreas, esophageal, liver, breast, prostate, thyroid, and
      renal carcinomas) are reviewed. The mechanisms by which obesity and other
      components of the CRS contribute to the pathogenesis of these cancers, such as
      hormone alterations and insulin- and insulin-like growth factor-dependent
      pathways of tumor pathogenesis, include the attending roles of inflammation and
      oxidative stress. Emphasis has been placed on obesity as a modifiable risk factor
      which, when addressed, provides a reduction in the rate of cancer deaths. In a
      second part to be published in the next issue of this journal, the relationship
      between diabetes and cancer will be reviewed in detail.

PMID- 22851965
TI  - MicroRNAs in insulin resistance and obesity.
AB  - MicroRNAs (miRNAs) are a class of short, single-stranded non-protein coding gene
      products which can regulate the gene expression through post-transcriptional
      inhibition of messenger RNA (mRNA) translation. They are known to be involved in
      many essential biological processes including development, insulin secretion, and
      adipocyte differentiation. miRNAs are involved in complex metabolic processes,
      such as energy and lipid metabolism, which have been studied in the context of
      diabetes and obesity. Obesity, hyperlipidemia (elevated levels of blood lipids),
      and insulin resistance are strongly associated with the onset of type 2 diabetes.
      These conditions are also associated with aberrant expression of multiple
      essential miRNAs in pancreatic islets of Langerhans and peripheral tissues,
      including adipose tissue. A thorough understanding of the physiological role
      these miRNAs play in these tissues, and changes to their expression under
      pathological conditions, will allow researchers to develop new therapeutics with
      the potential to correct the aberrant expression of miRNAs in type 2 diabetes and
      obesity.

PMID- 22851966
TI  - Detection of M-sequences from spike sequence in neuronal networks.
AB  - In circuit theory, it is well known that a linear feedback shift register (LFSR)
      circuit generates pseudorandom bit sequences (PRBS), including an M-sequence with
      the maximum period of length. In this study, we tried to detect M-sequences known
      as a pseudorandom sequence generated by the LFSR circuit from time series
      patterns of stimulated action potentials. Stimulated action potentials were
      recorded from dissociated cultures of hippocampal neurons grown on a
      multielectrode array. We could find several M-sequences from a 3-stage LFSR
      circuit (M3). These results show the possibility of assembling LFSR circuits or
      its equivalent ones in a neuronal network. However, since the M3 pattern was
      composed of only four spike intervals, the possibility of an accidental detection
      was not zero. Then, we detected M-sequences from random spike sequences which
      were not generated from an LFSR circuit and compare the result with the number of
      M-sequences from the originally observed raster data. As a result, a significant
      difference was confirmed: a greater number of "0-1" reversed the 3-stage M
      sequences occurred than would have accidentally be detected. This result suggests
      that some LFSR equivalent circuits are assembled in neuronal networks.

PMID- 22851967
TI  - The role of thoracic medial branch blocks in managing chronic mid and upper back
      pain: a randomized, double-blind, active-control trial with a 2-year followup.
AB  - Study Design. A randomized, double-blind, active-control trial. Objective. To
      determine the clinical effectiveness of therapeutic thoracic facet joint nerve
      blocks with or without steroids in managing chronic mid back and upper back pain.
      Summary of Background Data. The prevalence of thoracic facet joint pain has been
      established as 34% to 42%. Multiple therapeutic techniques utilized in managing
      chronic thoracic pain of facet joint origin include medial branch blocks,
      radiofrequency neurotomy, and intraarticular injections. Methods. This randomized
      double-blind active controlled trial was performed in 100 patients with 50
      patients in each group who received medial branch blocks with local anesthetic
      alone or local anesthetic and steroids. Outcome measures included the numeric
      rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work
      status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant
      improvement with significant pain relief and functional status improvement of 50%
      or more were observed in 80% of the patients in Group I and 84% of the patients
      in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of
      thoracic facets with or without steroids may provide a management option for
      chronic function-limiting thoracic pain of facet joint origin.

PMID- 22851968
TI  - Type II Diabetes Mellitus in Arabic-Speaking Countries.
AB  - The global epidemic of diabetes has not spared the Arabic-speaking countries,
      which have some of the highest prevalence of type II diabetes. This is
      particularly true of the Arab Gulf, a conglomerate of high income, oil-producing
      countries where prevalence rates are the highest. The prevalence rates among
      adults of the Arabic speaking countries as a whole range between 4%-21%, with the
      lowest being in Somalia and the highest in Kuwait. As economic growth has
      accelerated, so has the movement of the populations to urban centers where people
      are more likely to adopt lifestyles that embrace increased high-calorie food
      consumption and sedentary lifestyles. These factors likely contribute to the
      increased prevalence of obesity and diabetes in the Arabic speaking countries.

PMID- 22851969
TI  - Updated and new perspectives on diagnosis, prognosis, and therapy of malignant
      pheochromocytoma/paraganglioma.
AB  - Malignant pheochromocytomas/paragangliomas are rare tumors with a poor prognosis.
      Malignancy is diagnosed by the development of metastases as evidenced by
      recurrences in sites normally devoid of chromaffin tissue. Histopathological,
      biochemical, molecular and genetic markers offer only information on potential
      risk of metastatic spread. Large size, extraadrenal location, dopamine secretion,
      SDHB mutations, a PASS score higher than 6, a high Ki-67 index are indexes for
      potential malignancy. Metastases can be present at first diagnosis or occur years
      after primary surgery. Measurement of plasma and/or urinary metanephrine,
      normetanephrine and metoxytyramine are recommended for biochemical diagnosis.
      Anatomical and functional imaging using different radionuclides are necessary for
      localization of tumor and metastases. Metastatic pheochromocytomas/paragangliomas
      is incurable. When possible, surgical debulking of primary tumor is recommended
      as well as surgical or radiosurgical removal of metastases. I-131-MIBG
      radiotherapy is the treatment of choice although results are limited.
      Chemotherapy is reserved to more advanced disease stages. Recent genetic studies
      have highlighted the main pathways involved in pheochromocytomas/paragangliomas
      pathogenesis thus suggesting the use of targeted therapy which, nevertheless, has
      still to be validated. Large cooperative studies on tissue specimens and clinical
      trials in large cohorts of patients are necessary to achieve better therapeutic
      tools and improve patient prognosis.

PMID- 22851970
TI  - Hepatitis C variability, patterns of resistance, and impact on therapy.
AB  - Hepatitis C (HCV), a leading cause of chronic liver disease, cirrhosis, and
      hepatocellular carcinoma, is the most common indication for liver transplantation
      in the United States. Although annual incidence of infection has declined since
      the 1980s, aging of the currently infected population is expected to result in an
      increase in HCV burden. HCV is prone to develop resistance to antiviral drugs,
      and despite considerable efforts to understand the virus for effective
      treatments, our knowledge remains incomplete. This paper reviews HCV resistance
      mechanisms, the traditional treatment with and the new standard of care for
      hepatitis C treatment. Although these new treatments remain PEG-IFN-alpha- and
      ribavirin-based, they add one of the newly FDA approved direct antiviral agents,
      telaprevir or boceprevir. This new "triple therapy" has resulted in greater viral
      cure rates, although treatment failure remains a possibility. The future may
      belong to nucleoside/nucleotide analogues, non-nucleoside RNA-dependent RNA
      polymerase inhibitors, or cyclophilin inhibitors, and the treatment of HCV may
      ultimately parallel that of HIV. However, research should focus not only on
      effective treatments, but also on the development of a HCV vaccine, as this may
      prove to be the most cost-effective method of eradicating this disease.

PMID- 22851972
TI  - Lenalidomide in the treatment of chronic lymphocytic leukemia.
AB  - The application of nucleoside analogue-based chemotherapy and immunotherapy with
      rituximab or alemtuzumab has increased both response rate and survival in
      patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these
      therapies is curative, sequential therapeutic regimens are required. The majority
      of patients with relapsed or refractory CLL carry poor prognostic factors and
      show shorter overall survival and resistance to standard treatment. Numerous
      drugs have recently been approved for CLL therapy and many novel agents are under
      clinical investigation. The role of the tumor microenvironment and of immune
      dysfunction in CLL have allowed to enlarge the therapeutic armamentarium for CLL
      patients. This article will provide a comprehensive summary regarding mechanism
      of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical
      trials using lenalidomide alone or in combinations are discussed. Lenalidomide
      shows good activity also in relapsed/refractory or treatment-naive CLL patients.
      Definitive data from ongoing studies are needed to validate overall and
      progression-free survival. The toxicity profile might limit lenalidomide use
      because it can result in serious side effects, but largely controlled by gradual
      dose escalation. Further understanding of the exact mechanism of action in CLL
      will allow more efficacious use of lenalidomide alone or in combination regimens.

PMID- 22851971
TI  - Myelopoiesis and myeloid leukaemogenesis in the zebrafish.
AB  - Over the past ten years, studies using the zebrafish model have contributed to
      our understanding of vertebrate haematopoiesis, myelopoiesis, and myeloid
      leukaemogenesis. Novel insights into the conservation of haematopoietic lineages
      and improvements in our capacity to identify, isolate, and culture such
      haematopoietic cells continue to enhance our ability to use this simple organism
      to address disease biology. Coupled with the strengths of the zebrafish embryo to
      dissect developmental myelopoiesis and the continually expanding repertoire of
      models of myeloid malignancies, this versatile organism has established its niche
      as a valuable tool to address key questions in the field of myelopoiesis and
      myeloid leukaemogenesis. In this paper, we address the recent advances and future
      directions in the field of myelopoiesis and leukaemogenesis using the zebrafish
      system.

PMID- 22851973
TI  - Secondary primary malignancies in multiple myeloma: an old NEMESIS revisited.
AB  - The treatment of myeloma has undergone extraordinary improvements in the past
      half century. These advances have been accompanied by a concern for secondary
      primary malignancies (SPMs). It has been known for decades that extended therapy
      with alkylating chemotherapy agents, such as melphalan, carries an increased risk
      of therapy-related myelodysplastic syndrome and/or acute myeloid leukemia (t
      MDS/AML), with a cumulative risk as high as 10-15%. High-dose chemotherapy with
      autologous stem cell support became widely accepted for myeloma in the 1990s.
      Despite the use of high doses of melphalan, the risk of t-MDS/AML with this
      procedure is estimated to be less than 5%, with much of this risk attributable to
      pretransplant therapy. Recently, lenalidomide has come under scrutiny for its
      possible association with SPMs. It is too soon to declare a causal relationship
      at this time, but there appears to be an increased number of SPMs in reports from
      several studies using lenalidomide maintenance. Current studies should be amended
      and future studies planned to better define the risk of SPMs and the risk factors
      and mechanisms for its development. Patients should be educated regarding this
      potential concern but the current use of lenalidomide should not generally be
      altered until further data are available.

PMID- 22851974
TI  - Malignant mesothelioma of the tunica vaginalis: presenting with intermittent
      scrotal pain and hydrocele.
AB  - Paratesticular mesotheliomas are very rare tumors. In this paper, we present the
      management of a 38-year-old male patient with paratesticular malignant
      mesothelioma who was initially misdiagnosed and treated as recurrent
      epididymitis. After the final pathology report defining paratesticular
      mesothelioma during scrotal exploration, he underwent radical orchiectomy and
      hemiscrotal excision as a complementary, secondary procedure. His metastatic
      workup did not show any dissemination. Therefore, he did not receive any adjuvant
      treatment and remained disease-free for more than 2 years.

PMID- 22851975
TI  - Idiopathic pulmonary hemosiderosis in adults: a case report and review of the
      literature.
AB  - Idiopathic pulmonary hemosiderosis is a very rare condition rarely affecting
      adults and causing recurrent episodes of diffuse alveolar haemorrhage that may
      lead to lung fibrosis. Due to lack of pathognomonic findings, IPH diagnosis is
      established upon exclusion of all other possible causes of DAH in combination
      with specific pathologic findings revealing bland alveolar haemorrhage with
      absence of vasculitis and/or accumulation of immune complexes within lung
      parenchyma. Here we describe a rare case of idiopathic pulmonary hemosiderosis in
      an otherwise healthy 27-year-old Greek male patient with relapsing episodes of
      fever accompanied by general fatigue and discomfort. He was at this time point a
      light smoker and had been hospitalised once in the past for similar symptoms. His
      iron deficiency anemia coupled with chest high-resolution computed tomography and
      bronchoalveolar lavage revealed findings compatible with diffuse alveolar
      hemorrhage. After excluding all other sources of bleeding through extensive
      gastrointestinal workup and thorough immunologic profile, video-assisted thoracic
      lung biopsy was performed and the diagnosis of Idiopathic Pulmonary Hemosiderosis
      was established. Patient was treated with high doses of oral corticosteroids,
      leading to clinical response. We highlight the need for vigilance by the
      respiratory physician for the presence of DAH, a challenging, acute condition
      requiring early recognition along with identification of the underlying syndrome
      and appropriate treatment to achieve optimal results.

PMID- 22851976
TI  - Central neuropathic pain in a patient with multiple sclerosis treated
      successfully with topical amitriptyline.
AB  - Central neuropathic pain in patients with multiple sclerosis (MS) is a common
      debilitating symptom, which is mostly treated with tricyclic antidepressants or
      antiepileptics. Unfortunately, the use of these drugs is often limited due to
      adverse events. We investigated the analgesic effect of topical amitriptyline 5%
      and 10% cream in a patient with central neuropathic pain due to MS. The analgesic
      effect of topical amitriptyline cream on neuropathic pain was dose related. To
      evaluate whether this analgesic effect is due to the active compound or placebo,
      we conducted a double-blind placebo-controlled n-of-1 study with amitriptyline 5%
      cream and placebo. The instruction was to alternate the creams every week
      following the pattern ABAB, with an escape possibility of amitriptyline 10%
      cream. The result was a complete pain reduction after application of cream B,
      while most of the time cream A did not reduce the pain. The patient could
      correctly unblind both creams, determining B as active. She noted that in the
      week of using the active cream no allodynia was present, with a carryover effect
      of one day.

PMID- 22851977
TI  - Tuberculous lymphadenopathy mimicking pancreatic neoplasm.
AB  - Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary
      TB involvement. Because its symptoms and signs are often nonspecific, laboratory
      and imaging findings mimic other diseases including carcinoma. Therefore, the
      diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old
      woman who presented with abdominal pain, anorexia, and weight loss. She had been
      given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable
      except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan
      revealed multiple enlarged peripancreatic lymph nodes and concentric thickening
      of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and
      erosions. Histological examination showed epithelioid granulomas. Laparoscopy
      revealed numerous white tubercles diffusely covering the parietal peritoneum.
      Histopathological images of peripancreatic lymph node revealed large multiple
      caseating granulomas surrounded by Langhans_giant cells and epithelioid cells.
      Polymerase chain reaction and culture of the specimens were positive for
      Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis
      were finally diagnosed. She responded well to the antitubercular treatment.

PMID- 22851978
TI  - Hallucination in a seizure patient using levetiracetam: a case report.
AB  - Levetiracetam, a relatively new antiepileptic drug (AED), is used mainly as
      adjuvant and less as monotherapy of seizure. Though rare, Levetiracetam is
      reported to induce hallucination. To highlight the potential of this adverse drug
      event, we report a seizure-case that had auditory hallucination with
      Levetiracetam. A 32-year lady had 7-year history of unresponsive spells which
      increased in the last year, also occurred while asleep and were diagnosed as
      "generalized seizure" with video-EEG. With gradual optimization of Levetiracetam
      to 2250 mg, she continuously heard distressing sound of saw cutting wooden
      blocks. After 3-day continuous auditory hallucination, Levetiracetam had to be
      changed to sodium valproate.

PMID- 22851979
TI  - Intrauterine growth restriction and the fetal programming of the hedonic response
      to sweet taste in newborn infants.
AB  - Intrauterine growth restriction is associated with increased risk for adult
      metabolic syndrome and cardiovascular disease, which seems to be related to
      altered food preferences in these individuals later in life. In this study, we
      sought to understand whether intrauterine growth leads to fetal programming of
      the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24%
      sucrose solution or water and the taste reactivity was filmed and analyzed.
      Spearman correlation demonstrated a positive correlation between fetal growth and
      the hedonic response to the sweet solution in the first 15 seconds after the
      offer (r = 0.864, P = 0.001), without correlation when the solution given is
      water (r = 0.314, P = 0.455). In fact, the more intense the intrauterine growth
      restriction, the lower the frequency of the hedonic response observed. IUGR is
      strongly correlated with the hedonic response to a sweet solution in the first
      day of life in preterm infants. This is the first evidence in humans to
      demonstrate that the hedonic response to sweet taste is programmed very early
      during the fetal life by the degree of intrauterine growth. The altered hedonic
      response at birth and subsequent differential food preference may contribute to
      the increased risk of obesity and related disorders in adulthood in intrauterine
      growth-restricted individuals.

PMID- 22851981
TI  - Passing the shakespeare test.

PMID- 22851980
TI  - Television watching, diet quality, and physical activity and diabetes among three
      ethnicities in the United States.
AB  - Diabetes is a world-wide epidemic associated with multiple environmental factors.
      Prolonged television viewing (TV) time has been related to increased risk of
      obesity and type 2 diabetes in several studies. TV viewing has been positively
      associated with cardiovascular disease risk factors, lower energy expenditure,
      over-eating high-calorie and high-fat foods. The objective of this study was to
      assess the associations of hours of TV viewing with dietary quality, obesity and
      physical activity for three ethnic minorities with and without type 2 diabetes.
      Diet quality and physical activity were inversely related to prolonged TV
      viewing. African Americans and participants with type 2 diabetes were more likely
      to watch more than 4 hours of TV per day as compared to their counterparts. Diet
      quality was inversely associated with physical activity level. Future studies are
      needed to establish the risk factors of prolonged TV watching in adult
      populations for the development of diabetes or diabetes-related complications.
      Although strategies to reduce TV watching have been proven effective among
      children, few trials have been conducted in adults. Intervention trials aimed at
      reducing TV viewing targeting people with type 2 diabetes may be beneficial to
      improve dietary quality and physical activity, which may reduce diabetes
      complications.

PMID- 22851982
TI  - Hancocked: manulife and the limits of private health insurance.
AB  - Long-term care (LTC) insurance is a salesman's dream. Millions of well-heeled
      boomers, anxious to protect their estates from the random expropriation of
      institutional dependency - what a market! But for Manulife, bleeding $1.5 million
      a day in LTC claims through subsidiary John Hancock, LTC is a nightmare. Company
      spokesmen blame unexpected increases in life expectancy. But management's
      fundamental error was insuring correlated risks. Risk pooling works only when
      individual risks are uncorrelated. Increases in life expectancy affect all
      contracts together. Manulife made the same mistake selling equity-linked
      annuities with guaranteed floors - essentially insuring against stock market
      declines. Results for shareholders have been catastrophic. Top management,
      meanwhile, have been honoured and richly rewarded.

PMID- 22851983
TI  - Towards National Evidence-Informed Practice Guidelines for Canadian EMS: Future
      Directions.
AB  - In emergency medical services (EMS), like other areas of healthcare, a
      substantial knowledge-to-action gap exists between the results of research and
      widespread use in clinical practice. This paper reports on a national workshop
      held to develop a process for creating National EMS Evidence-Informed Clinical
      Guidelines in an attempt to improve knowledge translation. We discuss the lessons
      learned from the workshop and next steps in developing the guidelines. This
      process and its lessons are generalizable to other areas of healthcare seeking to
      develop evidence-based guidelines. National EMS Evidence-Informed Guidelines will
      likely be a meaningful knowledge translation activity for Canadian EMS.

PMID- 22851984
TI  - Quantifying limitations in chemotherapy data in administrative health databases:
      implications for measuring the quality of colorectal cancer care.
AB  - Reliable chemotherapy data are critical to evaluate the quality of care for
      patients with colorectal cancer who are treated with curative intent. In Canada,
      limitations in the availability and completeness of chemotherapy data exist in
      many administrative health databases. In this paper, we discuss these limitations
      and present findings from a chart review in Nova Scotia that quantifies the
      completeness of chemotherapy capture in existing databases. The results
      demonstrate that even basic information on cancer treatment in administrative
      databases can be insufficient to perform the types of analyses that most decision
      makers require for quality-of-care measurement.

PMID- 22851985
TI  - Diagnosing senescence: contributions to physician expenditure increases in
      british columbia, 1996/97 to 2005/06.
AB  - Conventional wisdom holds that Canada suffers from a physician shortage, yet
      expenditures for physicians' services continue to increase rapidly. We address
      this apparent paradox, analyzing fee-for-service payments to physicians in
      British Columbia in 1996/97 and 2005/06. Age-specific per capita expenditures
      (adjusted for fee changes) rose 1% per year over this period, adding $174 million
      to 2005/06 expenditures. We partition these increases into changes in the
      proportion of the population seeing a physician; the number of unique physicians
      seen; the number of visits per physician; and the average expenditure per visit.
      Expenditures on laboratory and imaging services, particularly for the elderly and
      very elderly, have increased dramatically. By contrast, primary care services for
      the non-elderly appear to have declined. The causes and health consequences of
      these large changes deserve serious attention.

PMID- 22851986
TI  - Do private clinics or expedited fees reduce disability duration for injured
      workers following knee surgery?
AB  - OBJECTIVE: To investigate the effect of workers' compensation policies related to
      expedited surgical fees and private clinic surgical setting on disability
      duration among injured workers. METHODS: The study included 1,380 injured workers
      with knee meniscectomy between 2001 and 2005 in British Columbia. Using linked
      workers' compensation claim and surgery/clinical records, wait time for surgery
      (time from last surgical consult to surgery) and time from surgery to return to
      work were computed and compared for workers who received care in public versus
      private facilities, and according to whether their surgeons received fees
      intended to expedite care. RESULTS: The public expedited group had the shortest
      disability duration from surgical consult to return to work; the expedited fee
      reduced the surgery wait time (~2 work weeks), and surgeries performed in public
      hospitals had a shorter return-to-work time (~1 work week). DISCUSSION: An
      overall difference of approximately three work weeks in disability duration may
      have meaningful clinical and quality-of-life implications for injured workers.
      However, minimal differences in expedited surgical wait times by private clinics
      versus public hospitals, and small differences in return-to-work outcomes
      favouring the public hospital group, suggest that a future economic evaluation of
      workers' compensation policies related to surgical setting is warranted.

PMID- 22851987
TI  - Population aging and the determinants of healthcare expenditures: the case of
      hospital, medical and pharmaceutical care in british columbia, 1996 to 2006.
AB  - THERE IS A GAP BETWEEN RHETORIC AND REALITY CONCERNING HEALTHCARE EXPENDITURES
      AND POPULATION AGING: although decades-old research suggests otherwise, there is
      widespread belief that the sustainability of the healthcare system is under
      serious threat owing to population aging. To shed new empirical light on this old
      debate, we used population-based administrative data to quantify recent trends
      and determinants of expenditure on hospital, medical and pharmaceutical care in
      British Columbia. We modelled changes in inflation-adjusted expenditure per
      capita between 1996 and 2006 as a function of two demographic factors (population
      aging and changes in age-specific mortality rates) and three non-demographic
      factors (age-specific rates of use of care, quantities of care per user and
      inflation-adjusted costs per unit of care). We found that population aging
      contributed less than 1% per year to spending on medical, hospital and
      pharmaceutical care. Moreover, changes in age-specific mortality rates actually
      reduced hospital expenditure by -0.3% per year. Based on forecasts through 2036,
      we found that the future effects of population aging on healthcare spending will
      continue to be small. We therefore conclude that population aging has exerted,
      and will continue to exert, only modest pressures on medical, hospital and
      pharmaceutical costs in Canada. As indicated by the specific non-demographic cost
      drivers computed in our study, the critical determinants of expenditure on
      healthcare stem from non-demographic factors over which practitioners, policy
      makers and patients have discretion.

PMID- 22851988
TI  - Advancing coordinated care in four provincial healthcare systems: evaluating a
      knowledge-exchange intervention.
AB  - OBJECTIVES: This research project created and evaluated a knowledge-exchange
      intervention designed to facilitate an increase in organizational readiness for
      implementing coordinated stroke care in four primarily rural provincial
      healthcare systems. INTERVENTION: Knowledge brokers were linked to networks
      within, across and outside the provinces to support, inform and disseminate best
      practice recommendations for coordinated stroke care within the provincial
      healthcare systems. FINDINGS: The intervention increased awareness and
      dissemination of recommendations, which stimulated the implementation of
      coordinated stroke care. Similar knowledge-exchange interventions might work in
      other healthcare jurisdictions with similar demographics, to promote evidence
      informed improvements in healthcare.

PMID- 22851989
TI  - Social Values, Regulatory Tensions and Professional Practices with
      Underprivileged Populations: The Case of Quebec's Oral Healthcare System.
AB  - OBJECTIVE: Dentists may experience frustration in their practice with people
      living on welfare, often perceiving them in a negative light. The difficulties
      encountered are detrimental to the patient-professional relationship and
      contribute to compromising access to care for this underprivileged population. In
      order to fully understand patient-professional interactions, we must consider the
      macroscopic contexts in which they occur. This paper examines the systemic
      influences of these interpersonal relationships to deepen our understanding of an
      important access-to-care determinant for people living on welfare. METHODS: Two
      frameworks are applied to the analysis of Quebec's oral healthcare system: the
      social values framework and the regulatory logics framework. RESULTS: Our
      assessment leads us to posit two phenomena: (1) certain negative stereotypes
      regarding patients living on welfare allow dentists to manage the inevitable
      regulatory conflicts (i.e., economic vs. professional) involved in their practice
      and (2) the behaviours of people living on welfare are frequently judged
      according to the social values embodied in the organization of Quebec's oral
      healthcare system, delivery and financing. CONCLUSION: Quebec's oral healthcare
      system fails to provide effective access to care for individuals living in
      poverty, and the government must significantly augment its involvement in this
      healthcare sector. Dentists should also understand the impact that systemic
      influences have on their rapport with people living on welfare. We argue that new
      orientations for the field of dental professional education should be
      considered.This paper was originally published in French, in the journal
      Pratiques et Organisation des Soins 2011 42(3).

PMID- 22851990
TI  - What should the optimal blood pressure goal be in patients with diabetes mellitus
      or chronic kidney disease?

PMID- 22851991
TI  - Are probiotics effective in management of irritable bowel syndrome?

PMID- 22851992
TI  - Non-syndromic cleft palate: analysis of TBX22 exon 5 gene mutation.
AB  - INTRODUCTION: This study aimed to investigate the mutation of T-box transcription
      factor TBX22 exon 5 in children with non-syndromic cleft palate. Four mutations
      in TBX22 exon 5 in X-linked cleft palate with ankyloglossia (CPX) patients had
      been identified in the previous studies. The study used the syndromic cleft
      palate susceptibility gene as a candidate gene for more common non-syndromic
      cleft palate. MATERIAL AND METHODS: A family-based study with parents and their
      children composing parent-child trios was performed in this research. Twenty
      children with non-syndromic cleft palate and 38 healthy parents were enrolled.
      TBX22 exon 5 was examined by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and DNA sequencing. The peaks of the sequence diagrams
      were analyzed using chromas221 and the results of sequencing were proofread using
      dnastar6.13. The index of the transmission disequilibrium test (TDT) was
      calculated through McNemar testing. RESULTS: We have not found the presence of
      any mutation of TBX22 exon 5 reported in syndromic cleft palate patients in
      references. The index of TDT was 0.56 and showed no statistically significant
      difference (p<0.05). No TBX22 exon 5 mutation was found in the 20 children.
      CONCLUSIONS: Mutation of TBX22 exon 5 is not associated with non-syndromic cleft
      palate in the population of Jiangzhe areas in China.

PMID- 22851993
TI  - beta-Thalassemia mutations and hemoglobinopathies in Adana, Turkey: results from
      a single center study.
AB  - INTRODUCTION: beta-Thalassemia and hemoglobinopathies are common genetic
      disorders in Turkey and in this retrospective study our aim was to determine the
      frequency of beta-thalassemia and hemoglobinopathies in Adana, which is one of
      the biggest cities located in the southern part of Turkey. MATERIAL AND METHODS:
      Data from 3000 individuals admitted to Seyhan Hereditary Blood Disorders Center
      in Adana were evaluated. The blood samples were collected into EDTA-containing
      tubes and hematological parameters were analyzed using an automatic cell counter.
      High performance liquid chromatography technique was used to determine the type
      of hemoglobin. Molecular screening of the beta-globin gene was performed with
      beta-Globin StripAssay. RESULTS: Of 3000 cases, 609 were diagnosed as beta
      thalassemia or hemoglobinopathy. We have found that the rates of occurrence of
      beta-thalassemia and hemoglobinopathies are 13.46% and 6.83% respectively in this
      area. We have identified 18 different beta-thalassemia mutations and three
      separate abnormal hemoglobins: HbS, HbD Los Angeles, and HbE. In molecular
      analyses, beta-thalassemia gene mutations of IVSI.110 (G > A), codon 8 (-AA),
      IVSI.1 (G > A), IVSI.6 (T > C), -30 (T > A), IVSII.1 (G > A), codon 39 (C > T),
      codon 44 (-C), IVSI.5 (G > C), codon 5 (-CT), codon 8/9 (+G), IVSII.745 (C > G),
      codon 22 (7bp del), -101(C > T), codon 36/37 (-T), IVSI.15 (T > G), codon 6 (-A),
      -88 (G > A) were detected. CONCLUSIONS: Considering the high incidence of
      mutations that we have found, beta-thalassemia and hemoglobinopathies still seem
      to be a public health problem in Adana.

PMID- 22851994
TI  - CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune
      thyroid diseases (Graves' disease and Hashimoto's thyroiditis).
AB  - INTRODUCTION: Autoimmune thyroid disease (AITD) is associated with both genetic
      and environmental factors which lead to the overactivity of immune system.
      Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main
      genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis,
      HT and Graves' disease, GD) development. The aim of the study was to evaluate the
      relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT
      and/or GD in Polish patients. MATERIAL AND METHODS: Molecular analysis involved
      AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group
      of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and
      CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction
      fragment length polymorphism method, using three restriction enzymes: Fnu4HI
      (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). RESULTS: Statistical analysis
      (chi(2) test) confirmed significant differences between the studied groups
      concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more
      frequent in AITD group and OR analysis suggested that it might increase the
      susceptibility to HT. In GD patients, OR analysis revealed statistically
      significant relationship with the presence of G allele. In controls, CTLA-4 A/A
      genotype frequency was significantly increased suggesting a protective effect.
      There were no statistically significant differences regarding frequencies of
      other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60
      A/G) between the studied groups. CONCLUSIONS: CTLA-4 A49G polymorphism seems to
      be an important genetic determinant of the risk of HT and GD in Polish patients.

PMID- 22851995
TI  - Up-regulated osteogenic transcription factors during early response of human
      periodontal ligament stem cells to cyclic tensile strain.
AB  - INTRODUCTION: As one group of periodontal ligament (PDL) cells, human periodontal
      ligament stem cells (hPDLSCs) have been isolated and identified as mesenchymal
      adult stem cells (MSCs) since 2004. It has been well accepted that PDL
      sensitively mediates the transmission of stress stimuli to the alveolar bone for
      periodontal tissue remolding. Besides, the direction of MSCs differentiation has
      been verified regulated by mechanical signals. Therefore, we hypothesized that
      tensile strain might act on hPDLSCs differentiation, and the early response to
      mechanical stress should be investigated. MATERIAL AND METHODS: The hPDLSCs were
      cultured in vitro and isolated via a magnetic activated CD146 cell sorting
      system. After investigation of surface markers and other experiments for
      identification, hPDLSCs were subjected to cyclic tensile strain at 3,000 ustrain
      for 3 h, 6 h, 12 h, and 24 h, without addition of osteogenic supplements. In the
      control groups, the cells were cultured in similar conditions without mechanical
      stimulation. Then osteogenic related genes and proteins were analyzed by RT-PCR
      and western blot. RESULTS: Cyclic tensile strain at 3,000 ustrain of 6 h, 12 h,
      and 24 h durations significantly increased mRNA and protein expressions of Satb2,
      Runx2, and Osx, which were not affected in unloaded hPDLSCs. CONCLUSIONS: We
      indicate that hPDLSCs might be sensitive to cyclic tensile strain. The
      significant increase of Runx2, Osx and Satb2 expressions may suggest an early
      response toward osteogenic orientation of hPDLSCs.

PMID- 22851996
TI  - Serum concentrations of adiponectin, leptin, resistin, ghrelin and insulin and
      their association with obesity indices in obese normo- and hypertensive patients 
      pilot study.
AB  - INTRODUCTION: Hypertension often coexists with obesity. Adipokines, ghrelin and
      insulin play important roles in the pathogenesis of both diseases. The aim of
      this study was to compare adiponectin, leptin, resistin, insulin and ghrelin mean
      serum concentrations and insulin resistance (HOMA-IR) in normo- and hypertensive
      patients with obesity. MATERIAL AND METHODS: ALL INCLUDED PATIENTS WERE DIVIDED
      ON THE FOLLOWING GROUPS: non-diabetic hypertensive patients with class I obesity
      (group A, n = 21) and class II/III obesity (group B, n = 10), and normotensive
      obese (class I)patients (group C, n = 7). Correlations between obesity indices
      (body mass index [BMI], waist-to-hip ratio [WHR], waist circumference [WC]), HOMA
      IR, and hormone and adipokine serum levels were also analyzed. RESULTS: Leptin
      level and HOMA-IR were significantly higher in group B compared to group C (9.74
      +/-3.88 ng/ml vs. 4.53 +/-3.00 ng/ml; p < 0.02 and 3.30 +/-1.59 vs. 1.65 +/-0.41;
      p < 0.02, respectively). A negative correlation between WC and adiponectin level
      (R = -0.6275; p < 0.01) and a positive correlation between WC and insulin
      concentration (R = 0.5122; p< 0.05) as well as with HOMA-IR (R = 0.5228; p <
      0.02) were found in group A. Negative correlations between BMI and ghrelin level
      (R = -0.7052; p < 0.05), WHR and adiponectin level (R = -0.6912; p < 0.05) and
      WHR and leptin level (R = -0.6728; p < 0.05) were observed in group B.
      CONCLUSIONS: Insulin resistance and leptin may be important pathogenic factors in
      hypertensive patients with severe obesity. Indices of abdominal obesity (WC, WHR)
      correlate better than BMI with HOMA-IR, insulin, adiponectin and leptin serum
      levels in hypertensive obese patients.

PMID- 22851997
TI  - The relationship of vitamin D with non-traditional risk factors for
      cardiovascular disease in subjects with metabolic syndrome.
AB  - INTRODUCTION: Several studies implicate an inverse relationship between 25
      hydroxy vitamin D (25(OH)Vit D) serum levels and metabolic syndrome (MetS). We
      sought to investigate a possible relationship between 25(OH)Vit D and emerging
      risk factors associated with MetS, such as small dense low-density lipoprotein
      cholesterol (sdLDL-C) concentration, lipoprotein-associated phospholipase A(2)
      (Lp-PLA(2)) activity and high-sensitivity C-reactive protein (hsCRP) levels.
      MATERIAL AND METHODS: We studied 110 consecutive otherwise healthy individuals.
      Of these, 52 were diagnosed with MetS and 58 who did not meet the MetS criteria
      served as controls. Low-density lipoprotein (LDL) subclass analysis was performed
      by polyacrylamide gel electrophoresis. Lp-PLA(2) activity was determined in total
      plasma by the trichloroacetic acid precipitation procedure. Serum 25(OH)Vit D was
      determined quantitatively by an enzyme immunoassay method. RESULTS: Metabolic
      syndrome subjects had significantly lower 25(OH)Vit D levels (11.8 [0.6-48.3]
      ng/ml; 29.5 [1.5-120.75] nmol/l) compared with controls (17.2 [4.8-62.4] ng/ml;
      43 [12-156] nmol/l, p = 0.027). Univariate regression analysis showed that
      25(OH)Vit D concentration was inversely related to triglycerides (r= - 0.416, p =
      0.003) and sdLDL-C (r= - 0.305, p = 0.004). There was no association of 25(OH)Vit
      D with waist circumference, blood pressure, high-density lipoprotein cholesterol
      (HDL-C), fasting glucose, Lp-PLA(2) and hsCRP. In multivariate regression
      analysis the relationship between 25(OH)Vit D and sdLDL-C became insignificant
      when triglycerides were included in the model. CONCLUSIONS: Subjects with MetS
      exhibit lower 25(OH)Vit D serum levels compared with non-MetS individuals. Low
      25(OH)Vit D is associated with higher sdLDL-C levels possibly through elevated
      triglycerides. No association between 25(OH)Vit D and Lp-PLA(2) or hsCRP was
      found.

PMID- 22851998
TI  - Risk factor reduction in progression of angiographic coronary artery disease.
AB  - INTRODUCTION: To investigate differences between outpatients with progressive and
      nonprogressive coronary artery disease (CAD) measured by coronary angiography.
      MATERIAL AND METHODS: Chart reviews were performed in patients in an outpatient
      cardiology practice having >= 2 coronary angiographies >= 1 year apart.
      Progressive CAD was defined as 1) new non-obstructive or obstructive CAD in a
      previously disease-free vessel; or 2) new obstruction in a previously non
      obstructive vessel. Coronary risk factors, comorbidities, cardiovascular events,
      medication use, serum low-density lipoprotein cholesterol (LDL-C), and blood
      pressure were used for analysis. RESULTS: The study included 183 patients, mean
      age 71 years. Mean follow-up duration was 11 years. Mean follow-up between
      coronary angiographies was 58 months. Of 183 patients, 108 (59%) had progressive
      CAD, and 75 (41%) had nonprogressive CAD. The use of statins, beta-blockers,
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and
      aspirin was not significantly different in patient with progressive CAD or
      nonprogressive CAD Mean arterial pressure was higher in patients with progressive
      CAD than in patients with nonprogressive CAD (97+/-13 mm Hg vs. 92+/-12 mm Hg)
      (p<0.05). Serum LDL-C was insignificantly higher in patients with progressive CAD
      (94+/-40 mg/dl) than in patients with nonprogressive CAD (81+/-34 mg/dl)
      (p=0.09). CONCLUSIONS: Our data suggest that in addition to using appropriate
      medical therapy, control of blood pressure and serum LDL-C level may reduce
      progression of CAD.

PMID- 22851999
TI  - Is plasma urotensin II concentration an indicator of myocardial damage in
      patients with acute coronary syndrome?
AB  - INTRODUCTION: Urotensin II (UII) is a vasoactive peptide secreted by endothelial
      cells. Increased plasma UII concentration was observed in patients with heart
      failure, liver cirrhosis, diabetic nephropathy and renal insufficiency. In
      patients with myocardial infarction both increased and decreased plasma UII
      concentrations were demonstrated. The aim of this study was to analyze whether
      plasma UII concentration reflects the severity of acute coronary syndrome (ACS).
      MATERIAL AND METHODS: One hundred and forty-nine consecutive patients with ACS,
      without age limit, were enrolled in the study. In all patients plasma
      concentration of creatinine, creatine kinase isoenzyme MB (CK-MB), troponin C, N
      terminal prohormone of brain natriuretic peptide (NT-pro BNP), and UII were
      assessed, and echocardiography was performed in order to assess the degree of
      left ventricular hypertrophy, ejection fraction (EF) and mass (LVM). RESULTS: In
      patients with the highest risk (TIMI 5-7) plasma UII concentration was
      significantly lower than in those with low risk (TIMI 1-2): 2.61+/-1.47 ng/ml vs.
      3.60+/-2.20 ng/ml. Significantly lower plasma UII concentration was found in
      patients with increased concentration of troponin C (2.60+/-1.52 ng/ml vs. 3.41+/
      2.09 ng/ml). There was a significant negative correlation between plasma UII
      concentration and TIMI score or concentration of troponin C, but not CK-MB.
      Borderline correlation between plasma UII and ejection fraction (R = 0.157;
      p=0.063) or NT-proBNP (R = - 0.156; p=0.058) was found. CONCLUSIONS: Decreased
      plasma urotensin II concentration in patients with ACS could be associated with
      more severe injury of myocardium.

PMID- 22852000
TI  - Dual-source computed tomography angiography and intravascular ultrasound
      assessment of restenosis in patients after coronary stenting for bifurcation left
      main stenosis: a pilot study.
AB  - INTRODUCTION: The aim of this prospective study was to evaluate the diagnostic
      accuracy of dual-source computed tomography coronary angiography (CTCA) compared
      to intravascular ultrasound (IVUS) for the detection of restenosis in patients
      who underwent coronary stenting for bifurcation left main (LM) stenosis. MATERIAL
      AND METHODS: Twenty-four patients underwent percutaneous intervention of the LM
      and were subsequently examined (median 9.2 months after procedure) using IVUS and
      CTCA for the detection of restenosis. RESULTS: Significant restenosis was
      detected according to IVUS examination in 6 patients (25%) and 8 segments (13%).
      Based on segment analysis, sensitivity, specificity, positive and negative
      predictive values of CTCA for the detection of restenosis were 89%, 68%, 32%,
      97%, respectively. There was moderate to good correlation between the minimal
      luminal area (MLA), measured by CTCA and IVUS for LM, the left anterior
      descending artery (LAD) and the left circumflex artery (LCx) (r=0.64, p<0.01;
      r=0.49, p=0.03; r=0.76, p<0.01, respectively). A Bland-Altman analysis showed
      that the MLAs measured by CTCA were underestimated in all segments (mean
      difference 1.67 +/-2.2 mm(2) for LM; 2.0 +/-2.0 mm(2) for LAD; 1.79 +/-1.79 mm(2)
      for LCx). An ROC analysis of the MLAs derived by CTCA for detecting significant
      stenosis was performed. The area under the curve for all analysed segments was
      0.73. CONCLUSIONS: The present study demonstrates that in patients after LM
      bifurcation stenting CTCA performs well in the exclusion of in-segment
      restenosis. However, due to the low positive predictive value of CTCA, the
      finding of any restenosis should be confirmed by invasive examination.

PMID- 22852001
TI  - Prognostic factors of mid-term clinical outcome in congestive heart failure
      patients discharged after acute decompensation.
AB  - INTRODUCTION: Risk stratification in congestive heart failure (CHF) patients is
      based on a variety of clinical and laboratory variables. We analysed renal
      function, BNP, water composition, echocardiographic and functional determinations
      in predicting mid-term outcome in CHF patients discharged after decompensation.
      MATERIAL AND METHODS: All subjects with NYHA class II-IV were enrolled at
      hospital discharge. NYHA class, BNP, water body composition, non-invasive cardiac
      output and echocardiogram were analysed. Death, cardiac transplantation and
      hospital readmission for CHF were scheduled. RESULTS: Two-hundred and thirty
      seven (64.5% males, age 71.1+/-10.1) patients were discharged after obtaining
      normal hydration; left ventricular ejection fraction (LVEF) was 43.2+/-16.2%,
      cardiac output was 3.8+/-1.1 l/min and BNP at discharge resulted 401.3+/-501.7
      pg/ml. During the 14-month follow-up 15 patients (6.3%) died, 1 (0.4%) underwent
      cardiac transplantation and 18 (7.6%) were readmitted for CHF (event group); in
      203 (85.6%) no events were observed (no-event group). Higher NYHA class (2.1+/
      0.7 vs. 1.9+/-0.4, p=0.01), BNP at discharge (750.2+/-527.3 pg/ml vs. 340.7+/
      474.3 pg/ml, p=0.002) and impaired LVEF (33.7+/-15.7% vs. 44.5+/-15.8%, p=0.0001)
      and creatinine (1.7+/-0.6 vs. 1.2+/-0.8 mg/dl, p=0.004) were noticed in the event
      group. At multivariate Cox analysis LVEF (p=0.0009), plasma creatinine (p=0.006)
      and BNP at discharge (p=0.001) were associated with adverse mid-term outcome.
      Kaplan-Meier survival curves demonstrated that adding cut-off points for
      creatinine 1.5 mg/dl and discharged BNP of 250 pg/ml discriminated significantly
      prognosis (p=0.0001; log rank 21.09). CONCLUSIONS: In predicting mid-term
      clinical prognosis in CHF patients discharged after acute decompensation, BNP at
      discharge >= 250 pg/ml added with plasma creatinine > 1.5 mg/dl are strong
      adverse predictors.

PMID- 22852002
TI  - A pilot study of circulating PPAR-gamma receptor protein in elderly patients with
      atrial fibrillation.
AB  - INTRODUCTION: The present study aimed to investigate the relationship between
      serum peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein
      concentration and inflammatory markers in elderly patients with atrial
      fibrillation (AF). MATERIAL AND METHODS: We enrolled a total of 73 elderly
      patients: 45 with AF as the test group and 28 in sinus rhythm as a control group.
      We assayed serum PPAR-gamma receptor protein, high-sensitivity C-reactive protein
      (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). The
      study protocol and written informed consent were approved by the Ethics Committee
      of Clinical Research, Peking University First Hospital. RESULTS: The
      concentration of PPAR-gamma receptor protein was lower in AF patients than that
      in the control group (p < 0.01), and the concentrations of hs-CRP, IL-6, and TNF
      alpha were higher than those in the control group (all p < 0.01). The PPAR-gamma
      level was negatively correlated with hs-CRP, IL-6, and left atrium diameter (LAD)
      level (all p < 0.05). On logistic regression analysis, PPAR-gamma, hs-CRP, TNF
      alpha and LAD level were associated with AF. CONCLUSIONS: Elderly patients with
      AF show an inflammatory state and atrial remodeling. The PPAR-gamma receptor
      protein concentration is inversely linked with inflammation in AF. As an
      important transcription factor regulating inflammatory gene expression, PPAR
      gamma may take part in the pathogenesis of AF.

PMID- 22852003
TI  - Systemic inflammation in peripheral arterial disease with or without coexistent
      chronic obstructive pulmonary disease: analysis of selected markers.
AB  - INTRODUCTION: Low-grade systemic inflammation plays an important role in the
      pathogenesis and natural history of chronic obstructive pulmonary disease (COPD)
      and peripheral arterial disease (PAD). The aim of the study was to analyze plasma
      concentrations of selected markers of inflammation in patients suffering from PAD
      with or without coexistent COPD. MATERIAL AND METHODS: Thirty patients (6 women)
      with advanced PAD (at least IIb stage according to Fontaine scale) hospitalized
      due to critical limb ischemia were examined. In all patients spirometry was
      performed to confirm or exclude COPD. Plasma concentration of IL-6, IL-8 and TNF
      alpha was measured using ELISA method. Statistical analysis was performed
      according to COPD status and according to smoking status independently. RESULTS:
      In the whole group of patients with PAD, COPD was recognized in 14 cases (for the
      first time in 10 cases). All patients were smokers (46.7% current, 53.3% ex
      smokers). We found a significant correlation between FEV1%N (percent of norm of
      first second expiratory volume) and the number of years of smoking (r = -0.39; p
      < 0.05). We found similar concentrations of IL-6 (2.54 pg/ml vs. 2.31 pg/ml), IL
      8 (8.55 pg/ml vs. 8.14 pg/ml, TNF-alpha (0.72 pg/ml vs. 1.75 pg/ml) in the
      COPD(+) group in comparison to the COPD(-) group (differences were not
      significant). We observed significant positive correlations (p < 0.05) between
      concentrations of measured markers and significant negative correlations between
      pain free walking distance and these markers. CONCLUSIONS: Our study confirmed
      coexistence of PAD with COPD. The character of inflammation is similar in these
      smoking-related diseases.

PMID- 22852004
TI  - Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients
      with and without microangiopathy.
AB  - INTRODUCTION: The aim of the study was to assess carotid intima-media thickness
      (CIMT) as a subclinical marker of atherosclerosis and arterial stiffness in type
      1 diabetic patients in relation to microangiopathy. MATERIAL AND METHODS: We
      included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years
      (interquartile range [IQR] 29-43), median disease duration 10 years (IQR: 9-14),
      mean +/- standard deviation (SD) glycated haemoglobin (HbA(1c)) 8.4 +/-1.4%.
      Fifty patients had at least one microangiopathic complication. Intima-media
      thickness (IMT) of the common carotid artery was measured using high resolution
      ultrasonography. Arterial stiffness was assessed using digital volume pulse
      analysis and tonometric measurement of wave reflection and central haemodynamics.
      RESULTS: SUBJECTS WITH MICROANGIOPATHY COMPARED WITH THOSE WITHOUT HAD HIGHER
      VALUES OF CIMT (MEDIAN [IQR]: 0.53 mm [0.45-0.60 mm] vs 0.47 mm [0.34-0.52 mm], p
      = 0.002), higher central augmentation index (CAI(x)) (mean +/- SD: 120.2 +/-19.4%
      vs. 110.5 +/-17.1%, p = 0.016) and higher peripheral augmentation index (PAI(x))
      (65.7 +/-18.1% vs. 57.2 +/-14.9%, p = 0.023). In the logistic regression
      analysis, the duration of diabetes, systolic and diastolic blood pressure,
      postprandial glycaemia, HbA(1c) and triglycerides predicted the presence of
      diabetic microangiopathy independently of age and sex. The CIMT, CAI(x) and
      PAI(x) were associated with the presence of diabetic microangiopathy only in the
      univariate model. CONCLUSIONS: In type 1 diabetic patients with microangiopathic
      complications, increased carotid IMT and arterial stiffness were observed. The
      study confirms the role of traditional risk factors for late diabetic
      complications, such as the duration of the disease and metabolic control in the
      development of microangiopathy.

PMID- 22852005
TI  - Latent autoimmune diabetes in adults in a population-based cohort of Polish
      patients with newly diagnosed diabetes mellitus.
AB  - INTRODUCTION: Latent autoimmune diabetes in adults (LADA) is a slowly developing
      form of autoimmune diabetes characterized by the presence of type 1 diabetes
      associated autoantibody. The aim of this study was to determine the incidence and
      characteristics of LADA in a population-based cohort of Polish patients with
      newly-diagnosed diabetes. MATERIAL AND METHODS: The study cohort was taken from
      the resident population of the city Bialystok, Poland, during the period 1
      January to 31 December 2003, aged 20-64 years. During this period we identified
      231 cases of diabetes. We measured glutamic acid decarboxylase (GADA) and insulin
      antibody (IAA), insulin, C peptide and glycated hemoglobin (HbA(1c)). Diagnosis
      of LADA was made according to Immunology Diabetes Society and Action LADA
      criteria. RESULTS: The incidence of LADA was 10 per year per 100 000 people. The
      proportion of patients with LADA was 8.9% among newly diagnosed cases with
      diabetes. Patients with LADA were younger at diagnosis (48.5 +/-9.4 years vs.
      54.8 +/-10.6 years, p < 0.01), had lower body mass index (26.9 +/-9.3 kg/m(2) vs.
      29.5 +/-5.2 kg/m(2), p < 0.05), C peptide (126 +/-127 pmol/l vs. 446 +/-592
      pmol/l, p < 0.001), and were less insulin resistant (HOMA IR 0.94 +/-0.85 vs.
      3.6+/-4.4, p < 0.001) compared to patients with type 2 diabetes. Glycated
      hemoglobin and fasting glucose were similar in patients with LADA and type 2
      diabetes. CONCLUSIONS: In addition to GAD, anti-insulin antibodies are useful for
      diagnosing autoimmune diabetes in adults. Patients with LADA have similar glucose
      control parameters (HbA(1c)) compared to patients with type 2 diabetes, although
      they are usually younger and have a lower body mass index. Patients with LADA
      make up a significant proportion of newly diagnosed people with diabetes mellitus
      in a Polish population.

PMID- 22852006
TI  - The comparison of common cancer types and the coincidence of concomitant chronic
      diseases between palliative home care patients in Lodz Voivodeship and the
      general Polish population.
AB  - INTRODUCTION: The continued growth in the number of elderly with cancer and age
      related chronic diseases will cause in Poland an increase in demand for
      palliative care. The aim of the study was to identify chronic comorbidities and
      cancer types in palliative home care patients and to compare their incidence with
      the general Polish population. MATERIAL AND METHODS: The data was obtained from
      543 patients who received palliative home care between 2005-2009. The occurrence
      of the most common chronic conditions such as arterial hypertension, ischemic
      heart disease, diabetes, chronic pulmonary diseases and central nervous system
      diseases were analysed together with the cancer types. RESULTS: The study group
      included 259 women (47.7%) and 284 men (52.3%) aged 25-91 years old. The most
      common primary neoplasm locations for men were lung (28.2% vs. 21.4% in general
      population) and colorectal cancer (18.7% vs. 11.4% in general population), and in
      women breast (19.7% vs. 22.8% in general population) and colorectal cancer (17.4%
      vs. 9.2% in general population). The incidence of ischemic heart disease,
      diabetes, and chronic pulmonary diseases was significantly different in
      comparison to the general populations (47.0% vs. 11.3%; 20.3% vs. 6.8%; 16.6% vs.
      27.5%, respectively). The mean number of concomitant diseases was 1.6 for women
      and 1.8 for men vs. 1.7 and 1.2 in the general Polish population respectively.
      CONCLUSIONS: The majority of the patients had concomitant disease, with
      cardiovascular diseases being most common. The most common primary neoplasm
      diagnoses in palliative home care patients were lung and colorectal cancer, which
      corresponds to the cancer prevalence in the general population.

PMID- 22852007
TI  - CA-125 concentration in serum and peritoneal fluid in patients with endometriosis
      - preliminary results.
AB  - INTRODUCTION: Cancer antigen 125 (CA-125), known as a biomarker for women genital
      tract malignancies, could be also useful in detecting and monitoring
      endometriosis. The aim of this study was to evaluate CA-125 in serum and
      peritoneal fluid (PF) as an indicator of endometriosis. MATERIAL AND METHODS:
      Fifty-six patients admitted to the First Department of Obstetrics and Gynaecology
      for diagnostic or therapeutic laparoscopy conducted for infertility, pelvic pain,
      suspected endometriosis or ovarian cysts entered the study. Those with
      laparoscopically confirmed endometriosis were assigned to group A, those without
      this condition to group B. Blood for CA-125 was taken prior to surgery,
      centrifuged and assayed in accordance with the manufacturer's instructions (VIDAS
      CA-125 II). Peritoneal fluid and an endometrial biopsy were taken during
      laparoscopy. Statistical comparisons were performed using Statistica 7.1.
      RESULTS: Group A consisted of 44 women with laparoscopically confirmed diagnosis;
      15 patients served as a control group. The mean value of CA-125 concentration in
      the endometriosis group was 33.98 U/ml, vs. 9.3 U/ml in the control group. The
      mean value of CA-125 in peritoneal fluid was 1241.88 U/ml in the non
      endometriosis group versus 2640.23 U/ml in the study group; both results were
      statistically significant (p < 0.05). There was a significant correlation between
      the stage of endometriosis and CA-125 plasma concentration (R = 0.5993, p <
      0.001). Cancer antigen 125 concentration in serum was a moderate predictor to
      distinguish between patients with and without endometriosis (AUC 0.794; 95% CI
      0.668-0.921; p = 0.001). CONCLUSIONS: Cancer antigen 125 is a well-known
      biomarker for endometriosis and helpful in daily clinical practice when
      endometriosis is suspected. The cut-off value in serum suggesting endometriosis
      with 68% sensitivity is 11 U/ml. This value is normal range for Ca-125
      concentration.

PMID- 22852008
TI  - Acute bronchiolitis in a paediatric emergency department of Northern Greece.
      Comparisons between two decades.
AB  - INTRODUCTION: Acute bronchiolitis is the most common lower respiratory tract
      infection in infants and toddlers concerning small bronchi or bronchioli. This
      retrospective study aimed to evaluate the incidence of acute bronchiolitis and
      the use of beta(2)-agonists between two different decades. MATERIAL AND METHODS:
      During 1990-1991 and 2001-2002, the files of the 2(nd) Paediatric Emergency
      Department of Aristotle University of Thessaloniki, AHEPA Hospital were reviewed
      and cases of acute bronchiolitis were recorded and analysed. RESULTS: During 1990
      1991, 14 538 children were identified with respiratory infections and
      bronchiolitis was diagnosed in 519/14 538 children (3.56%). Only 34 out of 519
      patients received nebulised salbutamol (6.6%) and 221/519 were hospitalized
      (42.6%). During 2001-2002, 9001 children were found to have respiratory tract
      infections and acute bronchiolitis was diagnosed in 641/9001 of them (7.12%). In
      total, 411/641 children (64.1%) received salbutamol and ipratropium, and 89/641
      patients (13.88%) were hospitalized. There was a predominance of male sex in both
      decades (p = 0.509). There was a statistically significant difference (p < 0.001)
      concerning the use of nebulised salbutamol with nebulised ipratropium between the
      two decades. Finally, during 2001-2002, the use of bronchodilators with or
      without corticosteroids was more frequent and it appears to be correlated with
      the reduced number of admissions to hospital (p < 0.05) compared with 1990-1991.
      CONCLUSIONS: There was an increase in the incidence of acute bronchiolitis during
      the last decade. The admission rate decreased probably due to the use of
      nebulized salbutamol and ipratropium, but further multicentre comparative trials
      are required to define the role of bronchodilators in the treatment of acute
      bronchiolitis.

PMID- 22852009
TI  - Exhaled breath 8-isoprostane as a marker of asthma severity.
AB  - INTRODUCTION: Oxidative stress is a non-specific feature of airway inflammation
      in asthmatics. 8-Isoprostane (8-IP), a prostaglandin-F(2alpha) isomer, is a
      relatively new marker of oxidative stress and may be measured in exhaled breath
      condensate (EBC) of patients with asthma. This research study aimed to evaluate
      the usefulness of EBC 8-IP as a marker of severity and control of severe adult
      asthma. MATERIAL AND METHODS: Twenty-seven severe, never-smoking asthmatics were
      studied. According to positive or negative reversibility testing, this group was
      subdivided into reversible and irreversible asthma groups. All participants were
      observed for 8 weeks during which they completed daily diary observations
      including day and night symptoms, number of awakenings, peak expiratory flow
      (PEF) variability, daily rescue medication usage and oral steroids consumption.
      They attended the clinic 3 times and on these occasions spirometry assessments,
      EBC collection and asthma control tests (ACT) were done. Two control groups were
      included: 11 healthy never-smokers and 16 newly diagnosed and never-treated, non
      smoking mild asthmatics. RESULTS: There were no statistically significant
      differences between severe asthma and healthy control or never-treated asthma
      groups in concentrations of EBC 8-IP (median and interquartile range: 4.67; 2.50
      27.92 vs. 6.93; 2.5-12.98 vs. 3.80; 2.50-10.73, respectively). No correlations
      were found between EBC 8-IP and asthma control parameters, such as ACT results,
      night and day symptoms, consumption of rescue medication, percentage of days free
      of oral steroids, PEF diurnal variation, lung function test results, forced
      expiratory volume in the 1 s reversibility, and markers of systemic inflammation.
      CONCLUSIONS: Our study results suggest that EBC 8-IP measurements are not useful
      for asthma monitoring.

PMID- 22852010
TI  - Association between primary nocturnal enuresis and habitual snoring in children
      with obstructive sleep apnoea-hypopnoea syndrome.
AB  - INTRODUCTION: Nocturnal enuresis (NE) and obstructive sleep apnoea-hypopnoea
      syndrome (OSAHS) are common problems during childhood, and population studies
      have reported a significant correlation between them. This study aimed to assess
      whether habitual snoring, mouth breathing and daytime sleepiness are associated
      with increased incidence of NE in children with OSAHS. MATERIAL AND METHODS:
      Polysomnography was performed in 42 children (66.7% males), 3.5-14.5 years old,
      who were evaluated for sleep-disordered breathing (SDB). RESULTS: Fourteen out of
      42 children (33.3%) presented mild, 16 out of 42 (38.1%) moderate and 12 out of
      42 (28.6%) severe degree of OSAHS. Apnea hypopnea index (AHI) ranged between 1.30
      94.20 (10.54 +/-15.67) events per hour of sleep. Nocturnal enuresis was reported
      in 7/42 (16.7%) of them. The main observed symptoms were snoring (90.5%),
      restless sleep (81%), mouth breathing (71.4%), nasal congestion (76.2%), and
      difficulty in arousal (52.4%). A statistically significant association was found
      between NE and mouth breathing (p = 0.014) or nasal congestion (p = 0.005).
      Children with OSAHS and NE had a higher arousal index (8.14 +/-8.05) compared
      with OSAHS children without NE (4.61 +/-7.95) (p = 0.19, z = -1.28). Snorers had
      higher levels of AHI (11.02 +/-16.37) compared with non-snorers (6.05 +/-4.81) (p
      = 0.33, z = -0.96), and habitually snorers (23/42, 54.76%) were at greater risk
      of having NE (4/23) than were non-snorers (0/4, p = 0.36). However, the
      prevalence of enuresis was not related to the severity of OSAHS, expressed as AHI
      (p = 0.70). CONCLUSIONS: Mouth breathing, nasal congestion and high threshold of
      arousal during sleep should be more carefully evaluated in cases of children with
      NE who do not respond to standard treatment and present SDB.

PMID- 22852011
TI  - Sorafenib in progressive castrate-resistant prostate cancer. Can we talk about a
      new therapeutic option?
AB  - Castrate-resistant prostate cancer represents a significant clinical challenge.
      Currently, the standard treatment for patients with castrate-resistant prostate
      cancer is chemotherapy, after which patients only receive symptomatic treatment.
      The available results of phase II clinical trials of sorafenib in patients with
      hormone-refractory prostate cancer indicate that, despite a relatively short
      progression-free survival, the treatment may be associated with good outcomes in
      terms of overall survival and maintenance of a good quality of life. The study
      presents the authors' critical opinions and observations about the usefulness of
      sorafenib in patients with prostate cancer.

PMID- 22852012
TI  - Mastocytosis in children and adults: clinical disease heterogeneity.
AB  - Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition
      consists of a heterogeneous group of disorders characterized by a pathological
      accumulation of mast cells in tissues including the skin, bone marrow, liver,
      spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in
      children and adults. Childhood onset mastocytosis is usually cutaneous and
      transient while in adults the condition commonly progresses to a systemic form.
      The heterogeneity of clinical presentation of mastocytosis is typically related
      to the tissue mast cell burden, symptoms due to the release of mast cell
      mediators, the type of skin lesions, the patient's age at the onset and
      associated haematological disorders. Therefore, a multidisciplinary approach is
      recommended. The present article provides an overview of clinical symptoms,
      diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and
      management of mastocytosis patients in clinical practice.

PMID- 22852013
TI  - Routine infant immunization with the 7- and 13-valent pneumococcal conjugate
      vaccines: current perspective on reduced-dosage regimens.
AB  - The 7 and 13-valent pneumococcal conjugate vaccines are mostly used in routine
      infant immunizations to prevent the development of pneumococcal disease.
      Currently, the dosing schedule approved and recommended for PCV7 and PCV13 in
      infants is 3 primary doses followed by a booster dose in the second year of life.
      However, a number of countries use a 2-dose only primary series with a booster
      dose in the second year of life. This review is aimed at providing the reader
      with a broad perspective on the currently available evidence which supports the
      clinical use of such reduced dosing schedules for the PCV7 and PCV13 vaccines.
      Recent evidence has been able to promulgate the immunogenicity and in some cases
      the effectiveness of the reduced dosing schedule for these vaccines. These
      findings may reduce costs as well as minimize supply and administration problems
      relating to the provision of the pneumococcal conjugated vaccines (PCVs).
      However, some caution is warranted since some inferior data have emerged with
      regards to the antibody immune response to certain pneumococcal serotypes
      following the implementation of such reduced dosing regimens. In addition, it is
      proposed that prospective surveillance be undertaken in all countries which have
      adopted the reduced-dosage immunization programs. This review may go some way in
      educating healthcare practitioners and healthcare policy decision makers at
      large.

PMID- 22852014
TI  - Concomitant administration of simvastatin with ivabradine in contrast to
      metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic
      rats.
AB  - INTRODUCTION: beta-Blockers play a significant role in therapeutic heart rate
      (HR) management and angina control. In patients who are unable to tolerate beta
      blockers ivabradine could be particularly useful. The aim of the study was to
      establish whether concomitant administration of simvastatin with ivabradine or
      metoprolol had any effect on rat HR and blood pressure (BP). MATERIAL AND
      METHODS: The experiments were performed in hyper- and normocholesterolemic
      outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks
      normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5%
      cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1%
      methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4)
      simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6)
      simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4
      week period. HR and BP measure were provided by an Isotec pressure transducer
      connected to a direct current bridge amplifier. For the further lipid profile
      examination, 0.25 ml of blood samples were taken. RESULTS: After administration
      of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic
      rats the mean HR was significantly reduced as compared to rats receiving
      simvastatin (312.0 +/-30.2 min(-1) vs. 430.7 +/-27.8 min(-1), p<0.05); (329.8 +/
      24.2 min(-1) vs. 420.5 +/-9.2 min(-1), p<0.05) or ivabradine alone (312.0 +/-30.2
      min(-1) vs. 350.2 +/-16.0 min(-1), p<0.05); (329.8 +/-24.2 min(-1) vs. 363.0 +/
      21.7 min(-1), p<0.05). CONCLUSIONS: Concomitant administration of simvastatin
      with ivabradine intensified slowing of HR, although it did not influence BP in
      normo-and hypercholesterolemic rats. Statin-induced intensification of HR
      deceleration after metoprolol administration was not observed.

PMID- 22852015
TI  - Strain of experimental animals and modulation of nitric oxide pathway: their
      influence on development of renal failure in an experimental model of hepatorenal
      syndrome.
AB  - INTRODUCTION: Pathomechanism of HRS is still poorly understood. The aim of our
      study was: (1) to test whether different strains of rats could develop typical
      HRS, and (2) to estimate the influence of activation and inhibition of nitric
      oxide for development of renal failure in course of HRS. MATERIAL AND METHODS:
      First, we used 16 of Wistar and 16 of Sprague-Dawley rats in galactosamine model
      of HRS. Next, we used 48 of SDR rats, which received saline, N-nitro-L-arginine
      or L-arginine before and after liver damage. Twenty four hours urine and blood
      samples were collected 48 h after saline or Ga1N injection. Biochemical
      parameters were determined in serum or urine and then creatinine clearance and
      osmolality clearance were calculated. Liver and kidney tissues were collected for
      histopathological examination. RESULTS: Liver failure developed in all tested
      groups with significant increase of bilirubin (p < 0.001), ALT (p < 0.001) and
      ammonia (p < 0.001). Nevertheless we did not achieve any evidence of renal
      failure in Wistar, but we found typical renal failure in Sprague-Dawley group
      with significant decrease in creatinine clearance (p < 0.0012) and increase in
      concentration of creatinine and urea (p < 0.001) and (p < 0.001) respectively.
      Inhibition of NOS prevented development of renal failure with significant
      improvement of GFR both before (p < 0.0017) and after (p < 0.003) Ga1N injection.
      Injection of L-arginine after Ga1N injection did not caused significant
      improvement of GFR. CONCLUSIONS: Our study showed, that genetic factors might be
      responsible for development of renal failure in course of HRS and nitric oxide
      play important role in acute model of this syndrome.

PMID- 22852016
TI  - Alginic acid sodium hydrogel co-transplantation with Schwann cells for rat spinal
      cord repair.
AB  - INTRODUCTION: The aim of the study was investigating the influence of Schwann
      cells-alginic acid sodium hydrogel co-transplantation on a rat model of spinal
      cord injury. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were randomly
      assigned to 4 groups: control, injury, injury with Schwann cell transplantation,
      and injury with Schwann cells-alginic acid sodium hydrogel co-transplantation.
      Gelatin sponge blocks containing a Schwann cell suspension were transplanted into
      the injury site in the Schwann cell group; Schwann cells seeded in alginic acid
      sodium hydrogel were transplanted into the injury site in the Schwann cells
      alginic acid sodium hydrogel group. At 12 h, 1, 3, 7, and 21 days after surgery,
      animals were assessed on the Basso, Beattie and Bresnahan (BBB) locomotor rating
      scale and then were sacrificed. RESULTS: In the injury group, Bcl-2
      immunoreactive cells peaked at 3 days after surgery, and the expression level
      returned to normal level at 14 days. In the co-transplantation group, Bcl-2
      immunoreactive cells in the spinal cord-transected segments were significantly
      increased until 7 days (p < 0.05) and remained at this level for more than 14
      days. In the injury group, the number of apoptotic cells was the highest, as
      compared with the other 3 groups, and peaked at 1 and 7 days following spinal
      cord injury, and they were mostly distributed in the white matter. The BBB scores
      were significantly higher in the Schwann cells-alginic acid sodium hydrogel
      transplantation group than in the simple injury and Schwann cell groups (p <
      0.05). CONCLUSIONS: Schwann cells-alginic acid sodium hydrogel co-transplantation
      could inhibit cellular apoptosis and enhance Bcl-2 expression in the spinal cord
      transected segments, and thereby promote the recovery of locomotor function after
      spinal cord injury, although it did not reach full rehabilitation.

PMID- 22852017
TI  - Medical errors - not only patients' problem.
AB  - INTRODUCTION: Medical error is often a traumatic experience not only for patients
      but also for doctors. However, patients as victims get much more publicity than
      those responsible for actual errors. The authors of the study conducted research
      to learn about Polish doctors' opinions on and reactions to medical errors and
      how they affect their further professional activity and psychological status. The
      aim of this study was to evaluate the impact of involvement in medical errors of
      doctors of different specialties and different age. MATERIAL AND METHODS: The
      research was conducted in a group of 100 doctors of different specialties.
      Respondents anonymously completed an experimental survey comprising 6 groups of
      multiple choice questions concerning such issues as awareness of the nature of
      medical error, legal liability of the perpetrator, consequences of medical error
      for further professional activity, the function of the Patients' Rights
      Representative and consequences of publishing the problem. RESULTS: The results
      indicate many negative effects of medical errors on physicians, such as common
      fear of making an error (82%), increased caution (52%), disadvantageous security
      measures while performing one's duties (57%), worsening of doctor-patient
      relations (67%), loss of social trust (62%) and increased treatment costs (40%).
      Forty five percent of the surveyed doctors declared that patients need the
      Patients' Rights Representative and 39% claimed it does not affect their work.
      CONCLUSIONS: Given the significant burden on physicians' health, well-being and
      performance associated with medical errors, health care institutions should take
      this into account and provide physicians with formal systems of support.

PMID- 22852018
TI  - Bilateral radioiodine uptake by the non-lactating breast of a single nulliparous
      woman: a case report and literature review.

PMID- 22852019
TI  - Clear cell adenocarcinoma of the uterine cervix in a 24-year-old woman. Case
      report and review of the literature.

PMID- 22852021
TI  - A longitudinal follow-up study of saffron supplementation in early age-related
      macular degeneration: sustained benefits to central retinal function.
AB  - Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it
      was shown that short-term Saffron supplementation improves retinal flicker
      sensitivity in early age-related macular degeneration (AMD). The aim of this
      study was to evaluate whether the observed functional benefits from Saffron
      supplementation may extend over a longer follow-up duration. Design.
      Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology
      setting. Participants. Twenty-nine early AMD patients (age range: 55-85 years)
      with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation
      (20 mg/day) over an average period of treatment of 14 (+/-2) months.
      Measurements. Clinical examination and focal-electroretinogram-(fERG-) derived
      macular (18 degrees ) flicker sensitivity estimate (Falsini et al. (2010)) every
      three months over a followup of 14 (+/-2) months. Retinal sensitivity, the
      reciprocal value of the estimated fERG amplitude threshold, was the main outcome
      measure. Results. After three months of supplementation, mean fERG sensitivity
      improved by 0.3 log units compared to baseline values (P < 0.01), and mean visual
      acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P
      < 0.01). These changes remained stable over the follow-up period. Conclusion.
      These results indicate that in early AMD Saffron supplementation induces macular
      function improvements from baseline that are extended over a long-term followup.

PMID- 22852020
TI  - HCV and lymphoproliferation.
AB  - Hepatitis C virus (HCV) infection is a serious public health problem because of
      its worldwide diffusion and sequelae. It is not only a hepatotropic but also a
      lymphotropic agent and is responsible not only for liver injury--potentially
      evolving to cirrhosis and hepatocellular carcinoma--but also for a series of
      sometimes severely disabling extrahepatic diseases and, in particular, B-cell
      lymphoproliferative disorders. These latter range from benign, but
      prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas.
      Analogously with Helicobacter pylori related lymphomagenesis, the study of the
      effects of viral eradication confirmed the etiopathogenetic role of HCV and
      showed it is an ideal model for better understanding of the molecular mechanisms
      involved. Concerning these latter, several hypotheses have been proposed over the
      past two decades which are not mutually exclusive. These hypotheses have
      variously emphasized the important role played by sustained stimulation of the
      immune system by HCV, infection of the lymphatic cells, viral proteins,
      chromosomal aberrations, cytokines, or microRNA molecules. In this paper we
      describe the main hypotheses that have been proposed with the corresponding
      principal supporting data.

PMID- 22852022
TI  - Xiaopiyishen Herbal Extract Granule Improves the Quality of Life among People
      with Fatigue-Predominant Subhealth and Liver-Qi Stagnation and Spleen-Qi
      Deficiency Syndrome.
AB  - To observe the effects of Xiaopiyishen Herbal Extract Granule (XPYS-HEG) on the
      quality of life in people with fatigue-predominant subhealth (FPSH) and liver-qi
      stagnation and spleen-qi deficiency syndrome, the participants were allocated
      randomly to the treatment group (XPYS, n = 100) and the control group (placebo, n
      = 100) in this study. The study period was 18 weeks (6 weeks for the intervention
      and 12 weeks for followup). The results show that there were no differences
      between the two groups for the scores of eight factors on the SF-36 (Chinese
      version of the SF-36 universal quality-of-life scale) at baseline. Compared with
      the baseline score, intervention with XPYS-HEG led to a significant increase in
      scores for the factor of bodily pain at the end of the 6th week. Compared with
      the score at the end of the 6th week, the score for the factor of mental health
      in the XPYS group significantly increased at the end of the 18th week. Therefore,
      XPYS-HEG could partially improve the quality of life for people with FPSH and
      liver-qi stagnation and spleen-qi deficiency syndrome, which can ease bodily
      pain, stimulate a positive mood, and ease a negative mood.

PMID- 22852023
TI  - Development of Specific Aspects of Spirituality during a 6-Month Intensive Yoga
      Practice.
AB  - The majority of research on yoga focuses on its psychophysiological and
      therapeutic benefits, while the spiritual aspects are rarely addressed. Changes
      of specific aspects of spirituality were thus investigated among 160 individuals
      (91% women, mean age 40.9 +/- 8.3 years; 57% Christians) starting a 2-year yoga
      teacher training. We used standardized questionnaires to measure aspects of
      spirituality (ASP), mindfulness (FMI-Freiburg Mindfulness Inventory), life
      satisfaction (BMLSS-Brief Multidimensional Life Satisfaction Scale), and positive
      mood (lightheartedness/relief). At the start of the course, scores of the
      respective ASP subscales for search for insight/wisdom, transcendence conviction,
      and conscious interactions/compassion were high, while those for religious
      orientation were low. Within the 6 month observation period, both conscious
      interactions/compassion (effect size, Cohen's d = .33), Religious orientation (d
      = .21), Lightheartedness/Relief (d = .75) and mindfulness (d = .53) increased
      significantly. Particularly non-religious/non-spiritual individuals showed
      moderate effects for an increase of conscious interactions/compassion. The
      results from this study suggest that an intensive yoga practice (1) may
      significantly increase specific aspects of practitioners' spirituality,
      mindfulness, and mood, (2) that these changes are dependent in part on their
      original spiritual/religious self-perception, and (3) that there are strong
      correlations amongst these constructs (i.e., conscious interactions/compassion,
      and mindfulness).

PMID- 22852025
TI  - Anatomically versus biologically unifocal prostate cancer: a pathological
      evaluation in the context of focal therapy.
AB  - OBJECTIVES: Since tumor focality in prostate cancer continues to be considered a
      major limitation for focal prostate therapy, in this study we attempted to
      compare the pathological features and the proportion of patients with
      anatomically unifocal versus biologically unifocal tumors (i.e. multifocal
      prostate cancer in which the secondary nonindex elements are small, low grade and
      clinically insignificant) who were suitable for focal therapy. METHODS: Ninety
      five consecutive whole mount laparoscopic radical prostatectomy samples underwent
      pathological assessment (from January 2007 to November 2009). Tumor focality,
      laterality, Gleason score and volume of individual foci, total tumor volume,
      pathological stage and surgical margin status were assessed. The index lesion was
      defined as the largest by volume. Patients suitable for focal ablation were
      defined as having tumors that were unifocal, organ confined, with a Gleason score
      (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate
      cancer, with one large index lesion and the remaining foci demonstrating features
      of clinically insignificant disease (total tumor volume of all secondary foci
      <=0.5 cm(3) with GS <= 6). RESULTS: Patients with biologically unifocal cancer
      had significantly lower total tumor volume (3.26 versus 7.28 cm(3); p < 0.001),
      index lesion volume (2.9 versus 7.16 cm(3); p < 0.001), rates of seminal vesicle
      invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4%
      versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p =
      0.018). The proportion of patients suitable for focal therapy was higher in the
      biologically unifocal versus anatomically unifocal cancer group, although without
      reaching statistical significance (65.3% versus 45.8%; p = 0.11). CONCLUSIONS:
      Patients with biologically unifocal tumors have better pathological outcome than
      those with anatomically unifocal disease. At present the assumption that
      multifocality should a priori exclude patients from any organ-preserving prostate
      cancer treatment is only theoretical and needs to be validated by future clinical
      trials since there are a large proportion of patients with multifocal disease
      apparently suitable for focal prostate therapy.

PMID- 22852024
TI  - In silico modelling of treatment-induced tumour cell kill: developments and
      advances.
AB  - Mathematical and stochastic computer (in silico) models of tumour growth and
      treatment response of the past and current eras are presented, outlining the aims
      of the models, model methodology, the key parameters used to describe the tumour
      system, and treatment modality applied, as well as reported outcomes from
      simulations. Fractionated radiotherapy, chemotherapy, and combined therapies are
      reviewed, providing a comprehensive overview of the modelling literature for
      current modellers and radiobiologists to ignite the interest of other
      computational scientists and health professionals of the ever evolving and
      clinically relevant field of tumour modelling.

PMID- 22852026
TI  - Does the type of urinary diversion affect the result of distal hypospadias
      repair? A prospective randomized trial.
AB  - PURPOSE: The purpose of this review is to evaluate different techniques in
      urinary diversion and urethral stenting in hypospadias surgery. PATIENTS AND
      METHODS: The surgical procedure included 192 tubularized incised plate (TIP)
      repairs for distal penile hypospadias. The patients were prospectively randomized
      into three groups: In group A, a urethral catheter was used as a stent and for
      diversion of urine (63 patients); in group B we use no urethral stenting (63
      patients), only a suprapubic catheter; and in group C we use a suprapubic
      diversion and we put a small catheter in the anterior urethra only (66 patients).
      The urethral catheter was removed in group A at the 6th-7th postoperative day and
      in group C the urethral stent was removed at the 3rd-4th postoperative day. The
      suprapubic catheter was removed in both groups B and C at the 7th-9th
      postoperative day. All patients received an injection of antibiotics in the
      morning of the operation and daily until the day of catheter removal. All of the
      operations were performed by the same surgeon. RESULTS: The mean ages of our
      patients were 3, 5, and 5 years in groups A, B, and C, respectively. The mean
      hospital stay was 5 days (3-8). Follow-up ranged from 8 to 48 months (mean of
      21.5 +/- 10.1 months). Bladder spasm was observed in 33% of our patients in group
      A while there were no cases of spasm in the other two groups with a statistically
      significant difference (p < 0.05). Fistula was reported in eight patients (12.7%)
      of our urethral catheter group A, while it was observed in three patients (2.3%)
      of our suprapubic diversion groups B and C with a statistically significant
      difference between the two groups (p < 0.05). Meatal stenosis was reported in
      eight patients in group B (12.7%; nonstented group) versus three patients of both
      groups A and C (2.4%; stented groups) with a statistically significant difference
      (p < 0.05). CONCLUSION: Suprapubic diversion is an important step in hypospadias
      repair as it provides a better success rate with a significantly lower rate of
      occurrence of fistula. However, the addition of a stent in the anterior urethra
      to suprapubic diversion avoids the development of meatal stenosis and also avoids
      the bladder spasm observed with a urethral catheter.

PMID- 22852027
TI  - Abiraterone and other novel androgen-directed strategies for the treatment of
      prostate cancer: a new era of hormonal therapies is born.
AB  - The number of life-prolonging therapies proven effective in the treatment of
      metastatic castrate-resistant prostate cancer (CRPC) has been limited until
      recently. In the past 2 years several such therapies have come to market. In
      2010, the autologous immunotherapy sipuleucel-T and the next-generation taxane
      cabazitaxel were approved in this setting. However, abundant evidence has shown
      that CRPC growth continues to be driven through androgen-dependent signaling.
      Both of these drugs fail to take advantage of this targetable oncogenic pathway.
      Potent specific inhibitors of cytochrome P450-17 have been engineered with the
      aim of suppressing androgen synthesis beyond that seen with the luteinizing
      hormone-releasing hormone agonists/antagonists. Abiraterone acetate was developed
      by rational design based on a pregnenolone parent structure. Its approval by the
      US Food and Drug Administration (FDA) was granted in 2011 based on phase III data
      demonstrating an overall survival advantage compared with placebo. More recently,
      other drugs that act along the androgen signaling pathway, such as orteronel (TAK
      700), galeterone (TOK-001), enzalutamide (MDV3100) and ARN-509, have shown
      promise in clinical trials. Some of these are expected to gain FDA approval in
      the near future. Here, we review abiraterone and other novel androgen-directed
      therapeutic strategies for the management of advanced prostate cancer.

PMID- 22852028
TI  - Sacral neuromodulation and refractory overactive bladder: an emerging tool for an
      old problem.
AB  - Overactive bladder (OAB) syndrome negatively affects the daily life of many
      people. Conservative treatments, such as antimuscarinics, do not always lead to
      sufficient improvement of the complaints and are often associated with
      considerable side effects resulting in treatment failure. In the case of failure
      or intolerable side effects, sacral neuromodulation (SNM) and botulinum toxin
      intravesical injections are minimally invasive and reversible alternatives.
      Currently, both SNM and botulinum toxin injection have FDA approval for use in
      OAB patients. This mini-review attempts to provide an update on SNM as a second
      line management of adults with refractory OAB, based on the available clinical
      evidence concerning the efficacy and safety.

PMID- 22852029
TI  - Retroperitoneal lymphadenectomy and resection for testicular cancer: an update on
      best practice.
AB  - Clinical stage I testicular nonseminomatous germ cell tumours (NSGCTs) are highly
      curable. Following orchidectomy a risk-adapted approach using active surveillance
      (AS), nerve-sparing retroperitoneal lymph node dissection (nsRPLND) and primary
      chemotherapy is recommended by the current guidelines. Clinical stage I is
      defined as negative or declining tumour markers to their half-life following
      orchidectomy and negative imaging studies of the chest, abdomen and
      retroperitoneum. Active surveillance can be performed in low-risk and in high
      risk NSGCTs with an anticipated relapse rate of about 15% and 50%. The majority
      of patients will relapse with good and intermediate prognosis tumours which have
      to be treated with three to four cycles chemotherapy. About 25-30% of these
      patients will have to undergo postchemotherapy retroperitoneal lymph node
      dissection (PC-RPLND) for residual masses. Primary chemotherapy with one or two
      cycles of cisplatin (Platinol), etoposide and bleomycin (PEB) is a therapeutic
      option for high-risk clinical stage I NSGCT associated with a recurrence rate of
      only 2-3% and a minimal acute and long-term toxicity rate. nsRPLND, if performed
      properly, will cure about 85% of all high-risk patients with clinical stage I
      NSGCT without the need for chemotherapy. PC-RPLND forms an integral part of the
      multimodality treatment in patients with advanced testicular germ cell tumours
      (TGCTs). According to current guidelines and recommendations, PC-RPLND in
      advanced seminomas with residual tumours is only indicated if a positron emission
      tomography (PET) scan performed 6-8 weeks after chemotherapy is positive. In
      nonseminomatous TGCT, PC-RPLND is indicated for all residual radiographic lesions
      with negative or plateauing markers. Loss of antegrade ejaculation represents the
      most common long-term complication which can be prevented by a nerve-sparing or
      modified template resection. The relapse rate after PC-RPLND is around 12%,
      however it increases significantly to about 45% in cases with redo RPLND and late
      relapses. Patients with increasing markers should undergo salvage chemotherapy.
      Only select patients with elevated markers who are thought to be chemorefractory
      might undergo desperation PC-RPLND if all radiographically visible lesions are
      completely resectable. PC-RPLND requires a complex surgical approach and should
      be performed in experienced, tertiary referral centres only.

PMID- 22852030
TI  - Biological reconstruction of bone defects: the role of the free fibula flap.
AB  - This review describes the kinds of skeletal bone defects in bones which develop
      through enchondral ossification. It focuses on the biological reconstruction of
      those defects according to the two main subtypes, intercalary and osteoarticular.
      We list the causes of bone defects and outline the different types and
      configurations that result from them. We then review the currently available
      reconstructive options according to the patient's age and describe the
      theoretical options as well. Finally, the history, surgical anatomy and clinical
      use of the free fibula flap will be reviewed. From our own clinical experience
      and review of the literature, we conclude that biological reconstruction is, in
      many ways, superior to alloplastic materials, especially in children, adolescents
      and young adults.

PMID- 22852031
TI  - Treatment of late-presenting developmental dislocation of the hip by progressive
      orthopaedic reduction and innominate osteotomy. Our results with more than 30
      years of follow up.
AB  - BACKGROUND: The treatment of late-presenting developmental dislocation of the hip
      (DDH) is still controversial. A consecutive series of 32 patients not previously
      treated (43 hips, Tonnis grade 3 or 4) underwent progressive closed reduction
      followed immediately by innominate osteotomy between 1964 and 1976. They were
      between 1.5 and 5 years old at the time of pelvic osteotomy. This study was
      designed to check the outcome of these patients more than 30 years later.
      METHODS: Eight patients living outside of France (North Africa) could not be
      reached and one patient had died of an unrelated cause. The remaining 23 patients
      (32 hips) were reviewed with clinical assessment (Merle d'Aubigne, Harris and
      Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] scores)
      and anteroposterior (AP) pelvic radiograph. This represents a 75% rate of follow
      up at 31 to 44 years post-operatively. RESULTS: In two patients, surgery was
      repeated due to residual subluxation. Only one patient needed a total hip
      replacement (THR) 33 years after initial treatment. The Merle d'Aubigne, Harris
      and WOMAC scores for the surviving hips were excellent or good in almost 80% of
      the cases. In four cases, radiographic signs "at risk for" osteoarthritis were
      present. Regularity of the femoral head was perfect in seven hips, regular in 18
      and irregular in six. According to the Severin-Seringe classification, 25 hips
      could be classified as group I (14 group IA and 11 group IB), three group II and
      three group VII. CONCLUSION: The long-term results of non-previously treated late
      presenting DDH by the technique of progressive closed reduction followed by
      innominate osteotomy are quite good and compare favourably with the long-term
      results of open reduction with the same osteotomy.

PMID- 22852032
TI  - Dysplasia of the hip in adolescent patients successfully treated for
      developmental dysplasia of the hip.
AB  - BACKGROUND: The purpose of this study was to analyze whether hips treated for
      developmental dysplasia of the hip (DDH) during infancy, which were clinically
      and radiologically fully normalized by walking age, may become dysplastic again
      during later growth. MATERIALS AND METHODS: A total of 150 patients were randomly
      selected out of a collective of 386 patients treated for DDH at the Department of
      Orthopaedics at the University of Zurich between 1993 and 2004. Treatment was
      started at birth and continued for 6 months. All patients had clinically and
      radiographically normal hips by walking age. The patients did not suffer from
      other diseases, in particular, neurological or neuromuscular diseases. RESULTS:
      We detected four female subjects among the 150 patients who had been successfully
      treated for DDH, who had developed dysplastic hips in early adolescence,
      necessitating acetabular surgery. CONCLUSION: The successful treatment of DDH in
      infancy does not ensure normal hip development; therefore, follow up into
      maturity may be recommended. LEVEL OF EVIDENCE: Level IV.

PMID- 22852033
TI  - Use of the Universal Clamp in adolescent idiopathic scoliosis for deformity
      correction and as an adjunct to fusion: 2-year follow-up.
AB  - PURPOSE: Among posterior surgical techniques for treating adolescent idiopathic
      scoliosis (AIS), hybrid constructs with pedicle-screw fixation in the lumbar
      spine and other anchors in the thoracic spine have been reported to provide to be
      of more physiological value in postoperative thoracic kyphosis than all-screw
      constructs. The Universial Clamp (UC) equipped with a soft sublaminar band is a
      relatively new thoracic anchor that can be used in hybrid constructs. A dedicated
      reduction tool that applies traction to the sublaminar band permits gentle
      translation of the thoracic curve to the precontoured fusion rods, which have
      been previously anchored distally by pedicle screws and proximally by hooks in a
      claw configuration. The aim of this study was to evaluate radiographic results of
      AIS treatment using UC hybrid constructs. METHODS: This was a prospective case
      series in which 29 consecutive patients with Lenke type 1, 2 or 3 AIS operated on
      by two surgeons in two centers were followed for 24 months. Necessity for
      anterior release was an exclusion criterion. RESULTS: A total of 5.4 +/- 1.4 UCs
      were used per patient. The major thoracic curve was reduced from 55 +/- 7 degrees
      to 14 +/- 6 degrees  at 1 month and 17 +/- 6 degrees  at 24 months (correction
      70%) without complications. In the patients who had less than 20 degrees  of T5
      T12 kyphosis preoperatively, thoracic kyphosis improved from 14 +/- 4 degrees  to
      20 +/- 3 degrees  at 3 months and 24 +/- 9 degrees  at 24 months. In the other
      patients, preoperative thoracic kyphosis (27 degrees  +/- 6 degrees ) was
      unchanged by the operation. CONCLUSION: UC hybrid constructs appear to safely
      provide satisfying coronal correction while consistently improving thoracic
      kyphosis in patients who also have preoperative hypokyphosis. We hypothesize that
      diminution in thoracic kyphosis was consistently avoided due to the
      straightforward traction of the spine to the fusion rods into which the chosen
      kyphosis was contoured by the surgeon before applying the reduction tool to the
      sublaminar bands.

PMID- 22852034
TI  - The role of postoperative furosemide therapy in the treatment of pleural effusion
      following kyphosis/scoliosis surgery.
AB  - PURPOSE: Retrospective analysis of data to determine if the use of postoperative
      furosemide therapy decreases the incidence of thoracocentesis in children and
      adolescents undergoing kyphosis or scoliosis surgery. One of the potential
      complications seen in patients undergoing scoliosis or kyphosis surgery is the
      development of a clinically symptomatic postoperative pleural effusion requiring
      thoracocentesis, which is an invasive procedure that is associated with
      discomfort to the patient and a minimal risk of an iatrogenic pneumothorax.
      METHODS: We retrospectively reviewed the medical records and X-rays of 190
      patients who had undergone corrective surgery for AIS/kyphosis. All patients
      underwent an ASF or an APSF or a PSF with a minimum 3 level costoplasty. We
      compared the rate of thoracocentesis in group 1 (no furosemide; 161 patients) to
      that in group 2 (furosemide; 29 patients). Follow-up chest radiographs were
      evaluated for a decrease or resolution of the effusion. RESULTS: In group 1, 26
      out of the 161 patients required thoracocentesis (16%); in group 2, only 1 out of
      the 29 patients underwent thoracocentesis (3.4%). CONCLUSIONS: Postoperative
      furosemide in patients who undergo significant pleural manipulation during spinal
      deformity surgery may decrease the incidence of clinically symptomatic pleural
      effusion requiring thoracocentesis. This study represents a true trend; however,
      a high level of significance can only be achieved by performing a larger
      randomized controlled study.

PMID- 22852035
TI  - Recurrence after surgery for equinus foot deformity in children with cerebral
      palsy: assessment of predisposing factors for recurrence in a long-term follow-up
      study.
AB  - BACKGROUND: Despite the large number of studies on the recurrence after surgery
      for equinus foot deformity in cerebral palsy (CP) patients, only a few
      investigations have reported long-term recurrence rates. Furthermore, little is
      known on the interval between the recurrent surgeries and the factors that lead
      to early recurrence. This study aimed to assess the overall recurrence after
      surgery for equinus foot deformity in patients with CP and to assess the factors
      associated with recurrence. We also aimed to determine the predisposing factors
      for early recurrence. METHODS: The medical records of 186 patients (308 feet)
      were reviewed in order to determine the recurrence after surgery for equinus foot
      deformity. The type of CP, type of surgery, age at surgery, functional mobility,
      passive dorsiflexion of the ankle at the last follow-up visit, and subsequent
      treatment were recorded. Kaplan-Meier survival analysis was employed, with the
      end point defined as reoperation. RESULTS: The mean age at surgery was 6.8 +/-
      2.5 years (range, 2.2-13.1). With the mean follow-up period of 11.3 years (range,
      7.2-17.7), the overall recurrence rate was 43.8%. The recurrence rate was highest
      among patients with hemiplegia (62.5%). The Kaplan-Meier survival without repeat
      surgery estimate was shown to be 88.6% at 5 years and 59.6% at 10 years. Among
      children with hemiplegia and diplegia, the younger children (<=8 years of age)
      showed a higher rate of recurrence compared with the older children (P = 0.04 and
      P = 0.01, respectively). In 41 feet (30.4%), reoperations were performed within 5
      years after the primary surgery. Early recurrence was most prevalent among
      children with hemiplegia (50.0%). In children with diplegia and quadriplegia, the
      younger children underwent the secondary operation later than the older children
      (P = 0.04 and P = 0.02, respectively). CONCLUSION: Recurrence after surgery for
      equinus foot deformity is common and the age at surgery has a significant
      influence on recurrence. Recurrence can occur at any age while the child is still
      growing; therefore, it is advised to follow those patients until they reach
      skeletal maturity. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 22852036
TI  - Elastic stable intramedullary nailing of tibial shaft fractures in children.
AB  - PURPOSE: Tibial fractures in the skeletally immature patient are usually treated
      without surgery. Elastic stable intramedullary nailing (ESIN) is commonly used
      for other diaphyseal fracture locations. Its advantages are minimally invasive
      surgery with a short hospitalisation duration, primary bone union and early
      weight bearing. The purpose of this study was to assess the use of ESIN in
      displaced tibial fractures in children over 6 years old and in cases of
      polytrauma. METHODS: This study was carried out over a 6-year period. The
      protocol consisted in ESIN of shaft tibial fractures in children over 6. Frontal
      and sagittal angulation, shortening and lengthening were measured on days 0, 2,
      15, 30 and 45. At 6 months, 1 and 2 years, the femoro-tibial axis and eventual
      shortening or lengthening were assessed. RESULTS: The study involved 86 children
      (average age 11.8 years). As early as day 30, all patients had normal knee
      mobility and symmetrical foot progress angle. At 2-year follow-up, frontal
      angulation and leg length discrepancy had decreased and affected 2% of patients.
      Four patients (5%) suffered from superficial infections. There were no cases of
      osteomyelitis or refracture. CONCLUSIONS: The fixation of paediatric diaphyseal
      tibial fractures with ESIN is a rapid, well-codified and effective method for
      treating long-bone closed fractures in children. Advantages over other fixation
      techniques include a lower infection rate, a lower refracture rate, ease of
      management, and an aesthetically pleasing scar.

PMID- 22852037
TI  - A new surgical technique for the treatment of supracondylar humerus fracture
      malunions in children.
AB  - PURPOSE: To report a new locking lateral closing wedge osteotomy used in
      repairing pediatric supracondylar humerus fracture malunions, which allows for
      coronal and sagittal plane correction of both cubitus varus and extension.
      METHODS: At our institution, eight children with cubitus varus resulting from
      prior supracondylar humerus fracture malunions underwent a new technique of
      lateral closing wedge osteotomy performed by a single surgeon. Preoperative
      templating created from radiographs of the bilateral upper extremities were
      compared with clinical exam to determine the angle of triangular bone that must
      be removed in order to correct the varus and any extension deformity. A lateral
      approach and subperiosteal dissection exposed the distal humerus. A transverse
      osteotomy created a proximal and distal fragment, from which two triangles of
      bone were removed. The fragments were reunited, parallel lateral pins were
      placed, and live imaging confirmed stable fixation. RESULTS: The osteotomy was
      performed in eight patients, with an average age of 6.3 years. The mean interval
      between the initial injury and corrective osteotomy was 2.4 years. All patients
      ended up with flexion of 130 degrees  or greater with full and symmetrical
      pronation and supination. The average ulnohumeral angular correction was 25.5
      degrees , which was within 2 degrees  of the uninvolved elbow in seven patients
      and to within 5 degrees  in one patient. Baumann's angle averaged 85.3 degrees 
      preoperatively and 73.7 degrees  postoperatively, with an average 70.2 degrees 
      in the uninvolved elbow. All of the patients healed with excellent clinical and
      radiographic alignment and complete function. There were no complications or
      revisions. CONCLUSION: Varus malunion is a well-described complication of
      pediatric supracondylar humerus fracture repairs, and many different osteotomy
      techniques have been described. This series demonstrates that an interlocking
      lateral wedge osteotomy with parallel lateral pin fixation can provide reliable
      correction of varus and extension deformity, with a minimal complication rate.

PMID- 22852038
TI  - RETRACTED ARTICLE: Reconstruction of acute closed traumatic extensor hallucis
      longus tendon rupture in adolescents with spastic cerebral palsy.

PMID- 22852039
TI  - The stener lesion.

PMID- 22852040
TI  - Photodynamic inactivation of mammalian viruses and bacteriophages.
AB  - Photodynamic inactivation (PDI) has been used to inactivate microorganisms
      through the use of photosensitizers. The inactivation of mammalian viruses and
      bacteriophages by photosensitization has been applied with success since the
      first decades of the last century. Due to the fact that mammalian viruses are
      known to pose a threat to public health and that bacteriophages are frequently
      used as models of mammalian viruses, it is important to know and understand the
      mechanisms and photodynamic procedures involved in their photoinactivation. The
      aim of this review is to (i) summarize the main approaches developed until now
      for the photodynamic inactivation of bacteriophages and mammalian viruses and,
      (ii) discuss and compare the present state of the art of mammalian viruses PDI
      with phage photoinactivation, with special focus on the most relevant mechanisms,
      molecular targets and factors affecting the viral inactivation process.

PMID- 22852041
TI  - Immune evasion strategies of ranaviruses and innate immune responses to these
      emerging pathogens.
AB  - Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect
      fish, amphibians and reptiles. For ecological and commercial reasons,
      considerable attention has been drawn to the increasing prevalence of ranaviral
      infections of wild populations and in aquacultural settings. Importantly, RVs
      appear to be capable of crossing species barriers of numerous poikilotherms,
      suggesting that these pathogens possess a broad host range and potent immune
      evasion mechanisms. Indeed, while some of the 95-100 predicted ranavirus genes
      encode putative evasion proteins (e.g., vIFalpha, vCARD), roughly two-thirds of
      them do not share significant sequence identity with known viral or eukaryotic
      genes. Accordingly, the investigation of ranaviral virulence and immune evasion
      strategies is promising for elucidating potential antiviral targets. In this
      regard, recombination-based technologies are being employed to knock out gene
      candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently,
      by using animal infection models with extensively characterized immune systems,
      such as the African clawed frog, Xenopus laevis, it is becoming evident that
      components of innate immunity are at the forefront of virus-host interactions.
      For example, cells of the macrophage lineage represent important combatants of RV
      infections while themselves serving as targets for viral infection, maintenance
      and possibly dissemination. This review focuses on the recent advances in the
      understanding of the RV immune evasion strategies with emphasis on the roles of
      the innate immune system in ranaviral infections.

PMID- 22852042
TI  - Molecular identification of chronic bee paralysis virus infection in Apis
      mellifera colonies in Japan.
AB  - Chronic bee paralysis virus (CBPV) infection causes chronic paralysis and loss of
      workers in honey bee colonies around the world. Although CBPV shows a worldwide
      distribution, it had not been molecularly detected in Japan. Our investigation of
      Apis mellifera and Apis cerana japonica colonies with RT-PCR has revealed CBPV
      infection in A. mellifera but not A. c. japonica colonies in Japan. The
      prevalence of CBPV is low compared with that of other viruses: deformed wing
      virus (DWV), black queen cell virus (BQCV), Israel acute paralysis virus (IAPV),
      and sac brood virus (SBV), previously reported in Japan. Because of its low
      prevalence (5.6%) in A. mellifera colonies, the incidence of colony losses by
      CBPV infection must be sporadic in Japan. The presence of the (-) strand RNA in
      dying workers suggests that CBPV infection and replication may contribute to
      their symptoms. Phylogenetic analysis demonstrates a geographic separation of
      Japanese isolates from European, Uruguayan, and mainland US isolates. The lack of
      major exchange of honey bees between Europe/mainland US and Japan for the recent
      26 years (1985-2010) may have resulted in the geographic separation of Japanese
      CBPV isolates.

PMID- 22852043
TI  - Legume lectins inhibit human parainfluenza virus type 2 infection by interfering
      with the entry.
AB  - Three lectins with different sugar binding specificities were investigated for
      anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The
      lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut
      agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2.
      Virus nucleoprotein (NP) gene synthesis was largely inhibited, but fusion (F) and
      hemagglutinin-neuraminidase (HN) gene syntheses were not. An indirect
      immunofluorescence study showed that Con A inhibited virus NP, F and HN protein
      syntheses, but LCA did not completely inhibit them, and that PNA inhibited only
      NP protein synthesis. Using a recombinant green fluorescence protein-expressing
      hPIV-2, without matrix protein (rghPIV-2DeltaM), it was found that virus entry
      into the cells was not completely prevented. The lectins considerably reduced the
      number of viruses released compared with that of virus infected cells. The
      lectins bound to cell surface within 10 min, and many aggregates were observed at
      30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules,
      but PNA had almost no effect on them. These results indicated that the inhibitory
      effects of the lectins were caused mainly by the considerable prevention of virus
      adsorption to the cells by the lectin binding to their receptors.

PMID- 22852044
TI  - T cell memory in the context of persistent herpes viral infections.
AB  - The generation of a functional memory T cell pool upon primary encounter with an
      infectious pathogen is, in combination with humoral immunity, an essential
      process to confer protective immunity against reencounters with the same
      pathogen. A prerequisite for the generation and maintenance of long-lived memory
      T cells is the clearance of antigen after infection, which is fulfilled upon
      resolution of acute viral infections. Memory T cells play also a fundamental role
      during persistent viral infections by contributing to relative control and
      immuosurveillance of active replication or viral reactivation, respectively.
      However, the dynamics, the phenotype, the mechanisms of maintenance and the
      functionality of memory T cells which develop upon acute/resolved infection as
      opposed to chronic/latent infection differ substantially. In this review we
      summarize current knowledge about memory CD8 T cell responses elicited during
      alpha-, beta-, and gamma-herpes viral infections with major emphasis on the
      induction, maintenance and function of virus-specific memory CD8 T cells during
      viral latency and we discuss how the peculiar features of these memory CD8 T cell
      responses are related to the biology of these persistently infecting viruses.

PMID- 22852046
TI  - Complete nucleotide sequence of watermelon chlorotic stunt virus originating from
      Oman.
AB  - Watermelon chlorotic stunt virus (WmCSV) is a bipartite begomovirus (genus
      Begomovirus, family Geminiviridae) that causes economic losses to cucurbits,
      particularly watermelon, across the Middle East and North Africa. Recently squash
      (Cucurbita moschata) grown in an experimental field in Oman was found to display
      symptoms such as leaf curling, yellowing and stunting, typical of a begomovirus
      infection. Sequence analysis of the virus isolated from squash showed 97.6-99.9%
      nucleotide sequence identity to previously described WmCSV isolates for the DNA A
      component and 93-98% identity for the DNA B component. Agrobacterium-mediated
      inoculation to Nicotiana benthamiana resulted in the development of symptoms
      fifteen days post inoculation. This is the first bipartite begomovirus identified
      in Oman. Overall the Oman isolate showed the highest levels of sequence identity
      to a WmCSV isolate originating from Iran, which was confirmed by phylogenetic
      analysis. This suggests that WmCSV present in Oman has been introduced from Iran.
      The significance of this finding is discussed.

PMID- 22852045
TI  - Influenza virus-mediated membrane fusion: determinants of hemagglutinin fusogenic
      activity and experimental approaches for assessing virus fusion.
AB  - Hemagglutinin (HA) is the viral protein that facilitates the entry of influenza
      viruses into host cells. This protein controls two critical aspects of entry:
      virus binding and membrane fusion. In order for HA to carry out these functions,
      it must first undergo a priming step, proteolytic cleavage, which renders it
      fusion competent. Membrane fusion commences from inside the endosome after a drop
      in lumenal pH and an ensuing conformational change in HA that leads to the
      hemifusion of the outer membrane leaflets of the virus and endosome, the
      formation of a stalk between them, followed by pore formation. Thus, the fusion
      machinery is an excellent target for antiviral compounds, especially those that
      target the conserved stem region of the protein. However, traditional ensemble
      fusion assays provide a somewhat limited ability to directly quantify fusion
      partly due to the inherent averaging of individual fusion events resulting from
      experimental constraints. Inspired by the gains achieved by single molecule
      experiments and analysis of stochastic events, recently-developed individual
      virion imaging techniques and analysis of single fusion events has provided
      critical information about individual virion behavior, discriminated intermediate
      fusion steps within a single virion, and allowed the study of the overall
      population dynamics without the loss of discrete, individual information. In this
      article, we first start by reviewing the determinants of HA fusogenic activity
      and the viral entry process, highlight some open questions, and then describe the
      experimental approaches for assaying fusion that will be useful in developing the
      most effective therapies in the future.

PMID- 22852047
TI  - Risk-based classification of leukemia by cytogenetic and multiplex molecular
      methods: results from a multicenter validation study.
AB  - Modern management of leukemia and selection of optimal treatment approaches
      entails the analysis of multiple recurrent cytogenetic abnormalities with
      independent diagnostic or prognostic value. We report the first multicenter
      validation of a multiplex molecular assay for 12 relevant fusion transcripts
      relative to cytogenetic methods. Performance was evaluated using a set of 280
      adult and pediatric acute or chronic leukemias representative of the variety of
      presentations and pre-analytical parameters encountered in the clinical setting.
      The positive, negative and overall agreements were >98.5% with high concordance
      at each of the four sites. Positive detection of cases with low blast count or at
      relapse was consistent with a method sensitivity of 1%. There was 98.7%
      qualitative agreement with independent reference molecular tests. Apparent false
      negatives corresponded to rare alternative splicing isoforms not included in the
      panel. We further demonstrate that clinical sensitivity can be increased by
      adding those rare variants and other relevant transcripts or submicroscopic
      abnormalities. We conclude that multiplex RT-PCR followed by liquid bead array
      detection is a rapid and flexible method attuned to the clinical laboratory
      workflow, complementing standard cytogenetic methods and generating additional
      information valuable for the accurate diagnosis, prognosis and subsequent
      molecular monitoring of leukemia.

PMID- 22852048
TI  - Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as
      a potent inhibitor of ER stress-induced XBP1 mRNA splicing.
AB  - The IRE1alpha-XBP1 pathway, a key component of the endoplasmic reticulum (ER)
      stress response, is considered to be a critical regulator for survival of
      multiple myeloma (MM) cells. Therefore, the availability of small-molecule
      inhibitors targeting this pathway would offer a new chemotherapeutic strategy for
      MM. Here, we screened small-molecule inhibitors of ER stress-induced XBP1
      activation, and identified toyocamycin from a culture broth of an Actinomycete
      strain. Toyocamycin was shown to suppress thapsigargin-, tunicamycin- and 2
      deoxyglucose-induced XBP1 mRNA splicing in HeLa cells without affecting
      activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK)
      activation. Furthermore, although toyocamycin was unable to inhibit IRE1alpha
      phosphorylation, it prevented IRE1alpha-induced XBP1 mRNA cleavage in vitro.
      Thus, toyocamycin is an inhibitor of IRE1alpha-induced XBP1 mRNA cleavage.
      Toyocamycin inhibited not only ER stress-induced but also constitutive activation
      of XBP1 expression in MM lines as well as primary samples from patients. It
      showed synergistic effects with bortezomib, and induced apoptosis of MM cells
      including bortezomib-resistant cells at nanomolar levels in a dose-dependent
      manner. It also inhibited growth of xenografts in an in vivo model of human MM.
      Taken together, our results suggest toyocamycin as a lead compound for developing
      anti-MM therapy and XBP1 as an appropriate molecular target for anti-MM therapy.

PMID- 22852049
TI  - HLA-DPbeta1 Asp84-Lys69 antigen-binding signature predicts event-free survival in
      childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC
      UKALL XI childhood ALL trial.
AB  - We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and 
      DP 3 supertypes had significantly worse event-free survival (EFS) than children
      with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding
      amino-acid polymorphisms (aspartic acid84-lysine69), we asked whether Asp84-Lys69
      or Asp84 alone were independent prognostic indicators in childhood acute
      lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients,
      stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5
      years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84
      Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7
      64.9%); non-Asp84-Lys69: 67.3% (63.4-71.2%); 2P=0.007). Post-relapse EFS was 10%
      less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse
      (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84
      compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS
      in the context of UKALL XI because of Asp84, and may have influenced post-relapse
      EFS. We speculate that this may be due to the recruitment of Asp84-Lys69
      restricted regulatory T cells in the context of this regimen, leading to the re
      emergence of residual disease. However, functional and molecular studies of the
      prognostic value of this and other HLA molecular signatures in other childhood
      ALL trials are needed.

PMID- 22852050
TI  - Recovery from cycling exercise: effects of carbohydrate and protein beverages.
AB  - The effects of different carbohydrate-protein (CHO + Pro) beverages were compared
      during recovery from cycling exercise. Twelve male cyclists (VO(2peak): 65 +/- 7
      mL/kg/min) completed ~1 h of high-intensity intervals (EX1). Immediately and 120
      min following EX1, subjects consumed one of three calorically-similar beverages
      (285-300 kcal) in a cross-over design: carbohydrate-only (CHO; 75 g per
      beverage), high-carbohydrate/low-protein (HCLP; 45 g CHO, 25 g Pro, 0.5 g fat),
      or low-carbohydrate/high-protein (LCHP; 8 g CHO, 55 g Pro, 4 g fat). After 4 h of
      recovery, subjects performed subsequent exercise (EX2; 20 min at 70% VO(2peak) +
      20 km time-trial). Beverages were also consumed following EX2. Blood glucose
      levels (30 min after beverage ingestion) differed across all treatments (CHO >
      HCLP > LCHP; p < 0.05), and serum insulin was higher following CHO and HCLP
      ingestion versus LCHP. Peak quadriceps force, serum creatine kinase, muscle
      soreness, and fatigue/energy ratings measured pre- and post-exercise were not
      different between treatments. EX2 performance was not significantly different
      between CHO (48.5 +/- 1.5 min), HCLP (48.8 +/- 2.1 min) and LCHP (50.3 +/- 2.7
      min). Beverages containing similar caloric content but different proportions of
      carbohydrate/protein provided similar effects on muscle recovery and subsequent
      exercise performance in well-trained cyclists.

PMID- 22852052
TI  - Consumption of a diet rich in cottonseed oil (CSO) lowers total and LDL
      cholesterol in normo-cholesterolemic subjects.
AB  - Animal data indicates that dietary cottonseed oil (CSO) may lower cholesterol;
      however, the effects of a CSO-rich diet have not been evaluated in humans. Thirty
      eight healthy adults (aged 18-40; 12 males, 26 females) consumed a CSO rich diet
      (95 g CSO daily) for one week. Anthropometric measurements were obtained, and
      blood was drawn pre- and post-intervention. Serum lipids (total cholesterol (TC),
      high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG),
      and free fatty acids (FFA)) were assayed. There was no change in weight or waist
      circumference among participants. There was no change in HDL (Pre: 1.27 +/- 0.4
      mmol/L; Post: 1.21 +/- 0.3 mmol/L) or TG (Pre: 0.91 +/- 0.6 mmol/L; Post: 1.06 +/
      1.0 mmol/L). Total cholesterol and LDL were reduced (TC Pre: 4.39 +/- 0.9
      mmol/L; Post: 4.16 +/- 0.8 mmol/L; LDL Pre: 2.70 +/- 0.8 mmol/L; Post: 2.47 +/-
      0.6 mmol/L). When data were grouped by sex, total cholesterol was reduced in
      female participants (Pre: 4.34 +/- 0.9 mmol/L; Post: 4.09 +/- 0.8 mmol/L).
      Consumption of a high fat, CSO-rich diet for one week reduced total cholesterol
      in female participants without reducing HDL.

PMID- 22852051
TI  - Ergogenic effects of beta-alanine and carnosine: proposed future research to
      quantify their efficacy.
AB  - beta-alanine is an amino acid that, when combined with histidine, forms the
      dipeptide carnosine within skeletal muscle. Carnosine and beta-alanine each have
      multiple purposes within the human body; this review focuses on their roles as
      ergogenic aids to exercise performance and suggests how to best quantify the
      former's merits as a buffer. Carnosine normally makes a small contribution to a
      cell's total buffer capacity; yet beta-alanine supplementation raises
      intracellular carnosine concentrations that in turn improve a muscle's ability to
      buffer protons. Numerous studies assessed the impact of oral beta-alanine intake
      on muscle carnosine levels and exercise performance. beta-alanine may best act as
      an ergogenic aid when metabolic acidosis is the primary factor for compromised
      exercise performance. Blood lactate kinetics, whereby the concentration of the
      metabolite is measured as it enters and leaves the vasculature over time, affords
      the best opportunity to assess the merits of beta-alanine supplementation's
      ergogenic effect. Optimal beta-alanine dosages have not been determined for
      persons of different ages, genders and nutritional/health conditions. Doses as
      high as 6.4 g day(-1), for ten weeks have been administered to healthy subjects.
      Paraesthesia is to date the only side effect from oral beta-alanine ingestion.
      The severity and duration of paraesthesia episodes are dose-dependent. It may be
      unwise for persons with a history of paraesthesia to ingest beta-alanine. As for
      any supplement, caution should be exercised with beta-alanine supplementation.

PMID- 22852053
TI  - Zinc intake and its dietary sources: results of the 2007 Australian National
      Children's Nutrition and Physical Activity Survey.
AB  - The current Australian Nutrient Reference Values (NRV) use different Estimated
      Average Requirements (EAR) for zinc for adolescent boys and girls compared to the
      previous recommendations. The adequacy of zinc intakes of 2-16 years old children
      (n = 4834) was examined in the 2007 Australian National Children's Nutrition and
      Physical Activity Survey. Zinc intakes were estimated from two 24-h recalls and
      compared with age- and gender-specific NRV. Food sources of zinc were assessed
      and compared with those of the 1995 National Nutrition Survey. The mean (SD) zinc
      intake was 10.2 (3.0) mg/day for all children. Nearly all children met the EAR
      for zinc except for 14-16 years old boys (29% did not meet EAR). Children (2-3
      years) were at highest risk of excessive zinc intakes with 79% exceeding the
      Upper Level of Intake. Meat and poultry; milk products; and cereals and cereal
      products contributed 68% of total zinc intake. The contribution of cereals to
      total zinc intake has increased significantly since 1995, due to the greater
      market-availability of zinc-fortified breakfast cereals. We conclude that sub
      groups of Australian children are at-risk of inadequate (boys 14-16 years) or
      excessive (children 2-3 years) zinc intakes, and monitoring of zinc status is
      required.

PMID- 22852054
TI  - Significant effect of a pre-exercise high-fat meal after a 3-day high
      carbohydrate diet on endurance performance.
AB  - We investigated the effect of macronutrient composition of pre-exercise meals on
      endurance performance. Subjects consumed a high-carbohydrate diet at each meal
      for 3 days, followed by a high-fat meal (HFM; 1007 +/- 21 kcal, 30% CHO, 55% F
      and 15% P) or high-carbohydrate meal (HCM; 1007 +/- 21 kcal, 71% CHO, 20% F and
      9% P) 4 h before exercise. Furthermore, just prior to the test, subjects in the
      HFM group ingested either maltodextrin jelly (M) or a placebo jelly (P), while
      subjects in the HCM ingested a placebo jelly. Endurance performance was measured
      as running time until exhaustion at a speed between lactate threshold and the
      onset of blood lactate accumulation. All subjects participated in each trial,
      randomly assigned at weekly intervals. We observed that the time until exhaustion
      was significantly longer in the HFM + M (p < 0.05) than in HFM + P and HCM + P
      conditions. Furthermore, the total amount of fat oxidation during exercise was
      significantly higher in HFM + M and HFM + P than in HCM + P (p < 0.05). These
      results suggest that ingestion of a HFM prior to exercise is more favorable for
      endurance performance than HCM. In addition, HFM and maltodextrin ingestion
      following 3 days of carbohydrate loading enhances endurance running performance.

PMID- 22852055
TI  - Effect of levan supplement in orange juice on weight, gastrointestinal symptoms
      and metabolic profile of healthy subjects: results of an 8-week clinical trial.
AB  - Levan is a commonly used dietary fiber of the fructans group. Its impact on
      health remains undetermined. This double blind controlled study aimed to
      investigate the effect of 8 weeks' daily consumption of 500 mL of natural orange
      juice enriched with 11.25 g of levan compared to the same amount of natural
      orange juice without levan on weight, gastrointestinal symptoms and metabolic
      profiles of 48 healthy volunteers. The statistical analyses compared between- and
      within-group findings at baseline, 4 weeks and study closure. The compared
      parameters were: weight, blood pressure, blood laboratory tests, daily number of
      defecations, scores of stool consistency, abdominal pain, bloating, gas,
      dyspepsia, vomiting and heartburn. Despite a higher fiber level recorded in the
      study group, there was no significant difference in the effect of the two kinds
      of juices on the studied parameters. Both juices decreased systolic and diastolic
      pressures, increased sodium level (within normal range), stool number, and
      bloating scores, and decreased gas scores. In conclusion, levan itself had no
      effect on weight, gastrointestinal symptoms or metabolic profile of healthy
      volunteers. Its possible effect on obese, hypertensive or hyperlipidemic patients
      should be investigated in further studies.

PMID- 22852056
TI  - Zinc and cancer: implications for LIV-1 in breast cancer.
AB  - Zinc is a trace mineral which is vital for the functioning of numerous cellular
      processes, is critical for growth, and may play an important role in cancer
      etiology and outcome. The intracellular levels of this mineral are regulated
      through the coordinated expression of zinc transporters, which modulate both zinc
      influx as well as efflux. LIV-1 (ZIP6) was first described in 1988 as an estrogen
      regulated gene with later work suggesting a role for this transporter in cancer
      growth and metastasis. Despite evidence of its potential utility as a target gene
      for cancer prognosis and treatment, LIV-1 has received relatively little
      attention, with only three prior reviews being published on this topic. Herein,
      the physiological effects of zinc are reviewed in light of this mineral's role in
      cancer growth with specific attention being given to LIV-1 and the potential
      importance of this transporter to breast cancer etiology.

PMID- 22852057
TI  - Zinc and regulation of inflammatory cytokines: implications for cardiometabolic
      disease.
AB  - In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade
      systemic inflammation and mild zinc deficiency highlights a role for zinc
      nutrition in the management of chronic disease. This review aims to evaluate the
      literature that reports on the interactions of zinc and cytokines. In humans,
      inflammatory cytokines have been shown both to up- and down-regulate the
      expression of specific cellular zinc transporters in response to an increased
      demand for zinc in inflammatory conditions. The acute phase response includes a
      rapid decline in the plasma zinc concentration as a result of the redistribution
      of zinc into cellular compartments. Zinc deficiency influences the generation of
      cytokines, including IL-1beta, IL-2, IL-6, and TNF-alpha, and in response to zinc
      supplementation plasma cytokines exhibit a dose-dependent response. The mechanism
      of action may reflect the ability of zinc to either induce or inhibit the
      activation of NF-kappaB. Confounders in understanding the zinc-cytokine
      relationship on the basis of in vitro experimentation include methodological
      issues such as the cell type and the means of activating cells in culture.
      Impaired zinc homeostasis and chronic inflammation feature prominently in a
      number of cardiometabolic diseases. Given the high prevalence of zinc deficiency
      and chronic disease globally, the interplay of zinc and inflammation warrants
      further examination.

PMID- 22852058
TI  - Alcohol exposure alters mouse lung inflammation in response to inhaled dust.
AB  - Alcohol exposure is associated with increased lung infections and decreased
      mucociliary clearance. Occupational workers exposed to dusts from concentrated
      animal feeding operations (CAFOs) are at risk for developing chronic inflammatory
      lung diseases. Agricultural worker co-exposure to alcohol and organic dust has
      been established, although little research has been conducted on the combination
      effects of alcohol and organic dusts on the lung. Previously, we have shown in a
      mouse model that exposure to hog dust extract (HDE) collected from a CAFO results
      in the activation of protein kinase C (PKC), elevated lavage fluid
      cytokines/chemokines including interleukin-6 (IL-6), and the development of
      significant lung pathology. Because alcohol blocks airway epithelial cell release
      of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung
      inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20%
      alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal
      inhalation method daily during the final three weeks. Bronchoalveolar lavage
      fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2-4 fold
      increase in lung and tracheal PKCepsilon (epsilon) activity in mice, but no such
      increase in PKCepsilon activity was observed in dust-exposed mice fed alcohol.
      Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage
      in response to dust than that observed in control mice instilled with HDE.
      TNFalpha levels were also inhibited in the alcohol and HDE-exposed mouse lung
      tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory
      aggregates clearly present in the tissue from HDE only exposed animals were not
      visually detectable in the HDE/alcohol co-exposure group. Statistically
      significant weight reductions and 20% mortality were also observed in the mice co
      exposed to HDE and alcohol. These data suggest that alcohol exposure depresses
      the ability of the lung to activate PKCepsilon-dependent inflammatory pathways to
      environmental dust exposure. These data also define alcohol as an important co
      exposure agent to consider in the study of inhalation injury responses.

PMID- 22852059
TI  - Effects of eating fresh lean pork on cardiometabolic health parameters.
AB  - High protein meat-based diets are commonly promoted for weight loss, supposedly
      by increasing satiety and energy expenditure. Pork is a good source of protein
      however little information on the metabolic effects of pork consumption exists.
      This pilot study aimed to examine whether regular consumption of fresh lean pork
      could improve body composition and cardiovascular risk factors in a 6 month
      parallel intervention trial. 164 overweight adults (mean BMI 32) were randomly
      assigned to incorporate up to 1 kg pork/week by substituting for other foods or
      maintain their habitual diet (control). Plasma levels of lipids, glucose and
      insulin, BMI, waist/hip circumference, blood pressure, heart rate and arterial
      compliance were measured at baseline and 3 and 6 months. Body composition was
      determined using dual energy X-ray absorptiometry. A total of 144 volunteers
      completed and volunteers in the pork group increased their intake 10 fold by
      substituting pork for mainly beef and chicken. After 3 months, there were
      significant (p <= 0.01) reductions in weight, BMI, waist circumference, % body
      fat, fat mass and abdominal fat in the pork group relative to controls, which
      persisted for 6 months. There was no change in lean mass, indicating that the
      reduction in weight was due to loss of fat mass. There were no significant
      effects on other metabolic parameters. Regular consumption of lean fresh pork may
      improve body composition.

PMID- 22852060
TI  - Selected vitamins and essential elements in meat from semi-domesticated reindeer
      (Rangifer tarandus tarandus L.) in mid- and northern Norway: geographical
      variations and effect of animal population density.
AB  - Meat samples (n = 100) were collected from semi-domesticated reindeer originating
      from 10 grazing districts in Norway. We aimed at studying concentrations,
      correlations, geographical variations and the effect of animal population density
      on vitamins A, B3, B7, B12 and E, and calcium, iron, zinc, selenium, chromium and
      cobalt. Mean concentrations of vitamins A, B3, B7; B12 and E were <5 ug, 6.6 mg,
      <0.5 ug, 4.7 ug and 0.5 mg/100 g wet weight, respectively. Concentrations of
      calcium, iron, zinc, selenium, chromium and cobalt were 4.7 mg, 2.8 mg, 6.4 mg,
      19.4 ug, 1.7 ug and 0.5 ug/100 g wet weight, respectively. Vitamin E and selenium
      were the nutrients that exhibited the largest geographical variations (p < 0.05),
      although no geographical gradient was observed for any of the studied nutrients.
      Age had a significant effect on zinc and selenium concentrations. Iron was
      significantly positive correlated with calcium (r = 0.3416, p < 0.01) and vitamin
      B12 with zinc (r = 0.35, p < 0.05). Reindeer from districts with low animal
      population density had significantly higher selenium concentration than those
      from districts with medium and high population densities (p < 0.01). Reindeer
      meat contained higher vitamin B12, iron, zinc and selenium concentrations when
      compared to Norwegian beef, lamb, mutton, pork and chicken meat.

PMID- 22852061
TI  - Exercise and amino acid anabolic cell signaling and the regulation of skeletal
      muscle mass.
AB  - A series of complex intracellular networks influence the regulation of skeletal
      muscle protein turnover. In recent years, studies have examined how cellular
      regulators of muscle protein turnover modulate metabolic mechanisms contributing
      to the loss, gain, or conservation of skeletal muscle mass. Exercise and amino
      acids both stimulate anabolic signaling potentially through several intracellular
      pathways including the mammalian target of rapamycin complex 1 and the mitogen
      activated protein kinase cell signaling cascades. As novel molecular regulators
      of muscle integrity continue to be explored, a contemporary analysis of the
      literature is required to understand the metabolic mechanisms by which
      contractile forces and amino acids affect cellular process that contribute to
      long-term adaptations and preservation of muscle mass. This article reviews the
      literature related to how exercise and amino acid availability affect cellular
      regulators of skeletal muscle mass, especially highlighting recent investigations
      that have identified mechanisms by which contractile forces and amino acids
      modulate muscle health. Furthermore, this review will explore integrated exercise
      and nutrition strategies that promote the maintenance of muscle health by
      optimizing exercise, and amino acid-induced cell signaling in aging adults
      susceptible to muscle loss.

PMID- 22852062
TI  - Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer.
AB  - Since ancient times, people have attributed a variety of health benefits to
      moderate consumption of fermented beverages such as wine and beer, often without
      any scientific basis. There is evidence that excessive or binge alcohol
      consumption is associated with increased morbidity and mortality, as well as with
      work related and traffic accidents. On the contrary, at the moment, several
      epidemiological studies have suggested that moderate consumption of alcohol
      reduces overall mortality, mainly from coronary diseases. However, there are
      discrepancies regarding the specific effects of different types of beverages
      (wine, beer and spirits) on the cardiovascular system and cancer, and also
      whether the possible protective effects of alcoholic beverages are due to their
      alcoholic content (ethanol) or to their non-alcoholic components (mainly
      polyphenols). Epidemiological and clinical studies have pointed out that regular
      and moderate wine consumption (one to two glasses a day) is associated with
      decreased incidence of cardiovascular disease (CVD), hypertension, diabetes, and
      certain types of cancer, including colon, basal cell, ovarian, and prostate
      carcinoma. Moderate beer consumption has also been associated with these effects,
      but to a lesser degree, probably because of beer's lower phenolic content. These
      health benefits have mainly been attributed to an increase in antioxidant
      capacity, changes in lipid profiles, and the anti-inflammatory effects produced
      by these alcoholic beverages. This review summarizes the main protective effects
      on the cardiovascular system and cancer resulting from moderate wine and beer
      intake due mainly to their common components, alcohol and polyphenols.

PMID- 22852063
TI  - Maternal zinc intakes and homeostatic adjustments during pregnancy and lactation.
AB  - Zinc plays critical roles during embryogenesis, fetal growth, and milk secretion,
      which increase the zinc need for pregnancy and lactation. Increased needs can be
      met by increasing the dietary zinc intake, along with making homeostatic
      adjustments in zinc utilization. Potential homeostatic adjustments include
      changes in circulating zinc, increased zinc absorption, decreased zinc losses,
      and changes in whole body zinc kinetics. Although severe zinc deficiency during
      pregnancy has devastating effects, systematic reviews and meta-analysis of the
      effect of maternal zinc supplementation on pregnancy outcomes have consistently
      shown a limited benefit. We hypothesize, therefore, that zinc homeostatic
      adjustments during pregnancy and lactation improve zinc utilization sufficiently
      to provide the increased zinc needs in these stages and, therefore, mitigate
      immediate detrimental effects due to a low zinc intake. The specific questions
      addressed are the following: How is zinc utilization altered during pregnancy and
      lactation? Are those homeostatic adjustments influenced by maternal zinc status,
      dietary zinc, or zinc supplementation? These questions are addressed by
      critically reviewing results from published human studies on zinc homeostasis
      during pregnancy and lactation carried out in different populations worldwide.

PMID- 22852065
TI  - A single-step purification and molecular characterization of functional Shiga
      toxin 2 variants from pathogenic Escherichia coli.
AB  - A one-step affinity chromatography method was developed to purify Shiga toxin 2
      variants (Stx2) Stx2a, Stx2c, Stx2d and Stx2g from bacterial culture
      supernatants. Analysis of the purified Stx2 variants by denaturing gel
      electrophoresis revealed 32 kDa and 7 kDa protein bands, corresponding to the
      Stx2A- and B-subunits, respectively. However, native gel electrophoresis
      indicated that purified Stx2c and Stx2d were significantly higher in molecular
      weight than Stx2a and Stx2g. In a cytotoxicity assay with Hela cells, the 50%
      cytotoxic dose of Stx2a and Stx2g were 100 pg and 10 pg, respectively, but 1 ng
      each for Stx2c and Stx2d. Interestingly, analysis of the 50% inhibitory dose in a
      cell-free translational system from rabbit reticulocyte lysates indicated that
      Stx2g had a lower capacity to inhibit protein synthesis than the other Stx2
      variants. The cytotoxicities in Hela cells were neutralized with an anti-Stx2B
      antibody and were denatured at 80  degrees C for 1 h. These findings demonstrated
      that Stx2 variants exhibited different toxicities, holotoxin structure, and
      stabilities using distinct systems for assessing toxin activities. The
      development of a simple method for purification of Stx2 variants will enable
      further studies of Stx2-mediated toxicity in various model systems.

PMID- 22852064
TI  - Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and
      infant brain development and function following maternal supplementation during
      pregnancy and lactation.
AB  - Scientific literature is increasingly reporting on dietary deficiencies in many
      populations of some nutrients critical for foetal and infant brain development
      and function. PURPOSE: To highlight the potential benefits of maternal
      supplementation with docosahexaenoic acid (DHA) and other important complimentary
      nutrients, including vitamin D, folic acid and iodine during pregnancy and/or
      breast feeding for foetal and/or infant brain development and/or function.
      METHODS: English language systematic reviews, meta-analyses, randomised
      controlled trials, cohort studies, cross-sectional and case-control studies were
      obtained through searches on MEDLINE and the Cochrane Register of Controlled
      Trials from January 2000 through to February 2012 and reference lists of
      retrieved articles. Reports were selected if they included benefits and harms of
      maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation
      during pregnancy and/or lactation. RESULTS: Maternal DHA intake during pregnancy
      and/or lactation can prolong high risk pregnancies, increase birth weight, head
      circumference and birth length, and can enhance visual acuity, hand and eye co
      ordination, attention, problem solving and information processing. Vitamin D
      helps maintain pregnancy and promotes normal skeletal and brain development.
      Folic acid is necessary for normal foetal spine, brain and skull development.
      Iodine is essential for thyroid hormone production necessary for normal brain and
      nervous system development during gestation that impacts childhood function.
      CONCLUSION: Maternal supplementation within recommended safe intakes in
      populations with dietary deficiencies may prevent many brain and central nervous
      system malfunctions and even enhance brain development and function in their
      offspring.

PMID- 22852067
TI  - Bacillus anthracis factors for phagosomal escape.
AB  - The mechanism of phagosome escape by intracellular pathogens is an important step
      in the infectious cycle. During the establishment of anthrax, Bacillus anthracis
      undergoes a transient intracellular phase in which spores are engulfed by local
      phagocytes. Spores germinate inside phagosomes and grow to vegetative bacilli,
      which emerge from their resident intracellular compartments, replicate and
      eventually exit from the plasma membrane. During germination, B. anthracis
      secretes multiple factors that can help its resistance to the phagocytes. Here
      the possible role of B. anthracis toxins, phospholipases, antioxidant enzymes and
      capsules in the phagosomal escape and survival, is analyzed and compared with
      that of factors of other microbial pathogens involved in the same type of
      process.

PMID- 22852068
TI  - Humanized-single domain antibodies (VH/VHH) that bound specifically to Naja
      kaouthia phospholipase A2 and neutralized the enzymatic activity.
AB  - Naja kaouthia (monocled cobra) venom contains many isoforms of secreted
      phospholipase A2 (sPLA(2)). The PLA(2) exerts several pharmacologic and toxic
      effects in the snake bitten subject, dependent or independent on the enzymatic
      activity. N. kaouthia venom appeared in two protein profiles, P3 and P5, after
      fractionating the venom by ion exchange column chromatography. In this study,
      phage clones displaying humanized-camel single domain antibodies (VH/V(H)H) that
      bound specifically to the P3 and P5 were selected from a humanized-camel VH/V(H)H
      phage display library. Two phagemid transfected E. coli clones (P3-1 and P3-3)
      produced humanized-V(H)H, while another clone (P3-7) produced humanized-VH. At
      the optimal venom:antibody ratio, the VH/V(H)H purified from the E. coli
      homogenates neutralized PLA(2) enzyme activity comparable to the horse immune
      serum against the N. kaouthia holo-venom. Homology modeling and molecular docking
      revealed that the VH/V(H)H covered the areas around the PLA(2) catalytic groove
      and inserted their Complementarity Determining Regions (CDRs) into the enzymatic
      cleft. It is envisaged that the VH/V(H)H would ameliorate/abrogate the principal
      toxicity of the venom PLA(2) (membrane phospholipid catabolism leading to
      cellular and subcellular membrane damage which consequently causes hemolysis,
      hemorrhage, and dermo-/myo-necrosis), if they were used for passive immunotherapy
      of the cobra bitten victim. The speculation needs further investigations.

PMID- 22852069
TI  - Yessotoxin as a tool to study induction of multiple cell death pathways.
AB  - This work proposes to use the marine algal toxin yessotoxin (YTX) to establish
      reference model experiments to explore medically valuable effects from induction
      of multiple cell death pathways. YTX is one of few toxins reported to make such
      induction. It is a small molecule compound which at low concentrations can induce
      apoptosis in primary cultures, many types of cells and cell lines. It can also
      induce a non-apoptotic form of programmed cell death in BC3H1 myoblast cell
      lines. The present contribution reviews arguments that this type of induction may
      have principal interest outside this particular example. One principal effect of
      medical interest may be that cancer cells will not so easily adapt to the
      synergistic effects from induction of more than one death pathway as compared to
      induction of only apoptosis.

PMID- 22852070
TI  - A knotless technique for kidney transplantation in the mouse.
AB  - Mouse models of kidney transplantation are important to study molecular
      mechanisms of organ transplant rejection as well as to develop new therapeutic
      strategies aimed at improving allograft survival. However, the surgical technique
      necessary to result in a viable allograft has traditionally proven to be complex
      and very demanding. Here, we introduce a new, simple, and rapid knotless
      technique for vessel anastomosis wherein the last stitch of the anastomosis is
      not tied to the short end of the upper tie as in the classical approach but is
      left free. This is a critical difference in that it allows the size of the
      anastomosis to be increased or decreased after graft reperfusion in order to
      avoid stenosis or bleeding, respectively. We compared the outcome of this new
      knotless technique (n = 175) with the classical approach (n = 122) in terms of
      local thrombosis or bleeding, time for anastomosis, and survival rates. By this
      modification of the suture technique, local thrombosis was significantly reduced
      (1.1% versus 6.6%), anastomosis time was less, and highly reproducible kidney
      graft survival was achieved (95% versus 84% with the classical approach). We
      believe that this knotless technique is easy to learn and will improve the
      success rates in the technically demanding model of mouse kidney transplantation.

PMID- 22852066
TI  - Bacillus anthracis edema factor substrate specificity: evidence for new modes of
      action.
AB  - Since the isolation of Bacillus anthracis exotoxins in the 1960s, the detrimental
      activity of edema factor (EF) was considered as adenylyl cyclase activity only.
      Yet the catalytic site of EF was recently shown to accomplish cyclization of
      cytidine 5'-triphosphate, uridine 5'-triphosphate and inosine 5'-triphosphate, in
      addition to adenosine 5'-triphosphate. This review discusses the broad EF
      substrate specificity and possible implications of intracellular accumulation of
      cyclic cytidine 3':5'-monophosphate, cyclic uridine 3':5'-monophosphate and
      cyclic inosine 3':5'-monophosphate on cellular functions vital for host defense.
      In particular, cAMP-independent mechanisms of action of EF on host cell signaling
      via protein kinase A, protein kinase G, phosphodiesterases and CNG channels are
      discussed.

PMID- 22852071
TI  - Inhibition of heme peroxidases by melamine.
AB  - In 2008 melamine-contaminated infant formula and dairy products in China led to
      over 50,000 hospitalizations of children due to renal injuries. In North America
      during 2007 and in Asia during 2004, melamine-contaminated pet food products
      resulted in numerous pet deaths due to renal failure. Animal studies have
      confirmed the potent renal toxicity of melamine combined with cyanuric acid. We
      showed previously that the solubility of melamine cyanurate is low at physiologic
      pH and ionic strength, provoking us to speculate how toxic levels of these
      compounds could be transported through the circulation without crystallizing
      until passing into the renal filtrate. We hypothesized that melamine might be
      sequestered by heme proteins, which could interfere with heme enzyme activity.
      Four heme peroxidase enzymes were selected for study: horseradish peroxidase
      (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2).
      Melamine exhibited noncompetitive inhibition of HRP (K(i)  9.5 +/- 0.7 mM), and
      LPO showed a mixed model of inhibition (K(i)  14.5 +/- 4.7 mM). The inhibition of
      HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine
      also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus,
      our results demonstrate that melamine inhibits the activity of three heme
      peroxidases.

PMID- 22852072
TI  - Identification of TNIP1 Polymorphisms by High Resolution Melting Analysis with
      Unlabelled Probe: Association with Systemic Lupus Erythematosus.
AB  - Background. TNFalpha-induced protein 3 (TNFAIP3) interacting with protein 1
      (TNIP1) acts as a negative regulator of NF-kappaB and plays an important role in
      maintaining the homeostasis of immune system. A recent genome-wide association
      study (GWAS) showed that the polymorphism of TNIP1 was associated with the
      disease risk of SLE in Caucasian. In this study, we investigated whether the
      association of TNIP1 with SLE was replicated in Chinese population. Methods. The
      association of TNIP1 SNP rs7708392 (G/C) was determined by high resolution
      melting (HRM) analysis with unlabeled probe in 285 SLE patients and 336 healthy
      controls. Results. A new SNP rs79937737 located on 5 bp upstream of rs7708392 was
      discovered during the HRM analysis. No association of rs7708392 or rs79937737
      with the disease risk of SLE was found. Furthermore, rs7708392 and rs79937737
      were in weak linkage disequilibrium (LD). Hypotypes analysis of the two SNPs also
      showed no association with SLE in Chinese population. Conclusions. High
      resolution melting analysis with unlabeled probes proves to be a powerful and
      efficient genotyping method for identifying and screening SNPs. No association of
      rs7708392 or rs79937737 with the disease risk of SLE was observed in Chinese
      population.

PMID- 22852073
TI  - Global HIV/AIDS Clinical and Translational Pharmacology.

PMID- 22852074
TI  - Understanding depression as it occurs in the context of post-traumatic stress
      disorder.

PMID- 22852076
TI  - Developing Targeted Health Service Interventions Using the PRECEDE-PROCEED Model:
      Two Australian Case Studies.
AB  - Aims and Objectives. This paper provides an overview of the applicability of the
      PRECEDE-PROCEED Model to the development of targeted nursing led chronic illness
      interventions. Background. Changing health care practice is a complex and dynamic
      process that requires consideration of social, political, economic, and
      organisational factors. An understanding of the characteristics of the target
      population, health professionals, and organizations plus identification of the
      determinants for change are also required. Synthesizing this data to guide the
      development of an effective intervention is a challenging process. The PRECEDE
      PROCEED Model has been used in global health care settings to guide the
      identification, planning, implementation, and evaluation of various health
      improvement initiatives. Design. Using a reflective case study approach, this
      paper examines the applicability of the PRECEDE-PROCEED Model to the development
      of targeted chronic care improvement interventions for two distinct Australian
      populations: a rapidly expanding and aging rural population with unmet palliative
      care needs and a disadvantaged urban community at higher risk of cardiovascular
      disease. Results. The PRECEDE-PROCEED Model approach demonstrated utility across
      diverse health settings in a systematic planning process. In environments
      characterized by increasing health care needs, limited resources, and growing
      community expectations, adopting planning tools such as PRECEDE-PROCEED Model at
      a local level can facilitate the development of the most effective interventions.
      Relevance to Clinical Practice. The PRECEDE-PROCEED Model is a strong theoretical
      model that guides the development of realistic nursing led interventions with the
      best chance of being successful in existing health care environments.

PMID- 22852075
TI  - Ductal carcinoma in situ of the breast.
AB  - Ductal carcinoma in situ (DCIS) of the breast represents a complex, heterogeneous
      pathologic condition in which malignant epithelial cells are confined within the
      ducts of the breast without evidence of invasion. The increased use of screening
      mammography has led to a significant shift in the diagnosis of DCIS, accounting
      for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with
      an overall increase in incidence. As the incidence of DCIS increases, the
      treatment options continue to evolve. Consistent pathologic evaluation is crucial
      in optimizing treatment recommendations. Surgical treatment options include
      breast-conserving surgery (BCS) and mastectomy. Postoperative radiation therapy
      in combination with breast-conserving surgery is considered the standard of care
      with demonstrated decrease in local recurrence with the addition of radiation
      therapy. The role of endocrine therapy is currently being evaluated. The
      optimization of diagnostic imaging, treatment with regard to pathological risk
      assessment, and the role of partial breast irradiation continue to evolve.

PMID- 22852077
TI  - PET Imaging in Recurrent Medullary Thyroid Carcinoma.
AB  - Purpose. To perform an overview about the role of positron emission tomography
      (PET) or PET/computed tomography (PET/CT) using different radiopharmaceuticals in
      recurrent medullary thyroid carcinoma (MTC) based on biochemical findings
      (increased tumor marker levels after primary surgery). Methods. A comprehensive
      literature search of studies published in PubMed/MEDLINE, Scopus, and Embase
      databases through February 2012 regarding PET or PET/CT in patients with
      recurrent MTC was performed. Results. Twenty-nine studies comprising 714 patients
      with suspected recurrent MTC were retrieved. Twenty-seven articles evaluated the
      role of fluorine-18-fluorodeoxyglucose (FDG) PET or PET/CT in recurrent MTC with
      conflicting results. Diagnostic accuracy of FDG-PET and PET/CT increased in MTC
      patients with higher calcitonin and carcinoembryonic antigen values, suggesting
      that these imaging methods could be very useful in patients with more advanced
      and aggressive disease. Eight articles evaluated the role of fluorine-18
      dihydroxyphenylalanine (FDOPA) PET or PET/CT in recurrent MTC reporting promising
      results. Overall, FDOPA seems to be superior but complementary compared to FDG in
      detecting recurrent MTC. Few studies evaluating other PET tracers are also
      discussed. Conclusions. PET radiopharmaceuticals reflect different metabolic
      pathways in MTC. FDOPA seems to be the most useful PET tracer in detecting
      recurrent MTC based on rising levels of tumor markers. FDG may complement FDOPA
      in patients with more aggressive MTC.

PMID- 22852079
TI  - Angiogenic signalling pathways altered in gliomas: selection mechanisms for more
      aggressive neoplastic subpopulations with invasive phenotype.
AB  - The angiogenesis process is a key event for glioma survival, malignancy and
      growth. The start of angiogenesis is mediated by a cascade of intratumoural
      events: alteration of the microvasculature network; a hypoxic microenvironment;
      adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a
      chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia
      phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma
      invasiveness and angiogenesis. Clones of neoplastic cells with stem cell
      characteristics are selected by HIF-1. These cells, called "glioma stem cells"
      induce the synthesis of vascular endothelial growth factor. This factor is a
      pivotal mediator of angiogenesis. To elucidate the role of these angiogenic
      mediators during glioma growth, we have used a rat endogenous glioma model.
      Gliomas induced by prenatal ENU administration allowed us to study angiogenic
      events from early to advanced tumour stages. Events such as microvascular
      aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth.
      Our data showed that for the treatment of gliomas, developing anti-angiogenic
      therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be
      considered to be a useful option to check novel designs of these treatment
      strategies.

PMID- 22852078
TI  - NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases.
AB  - Anaplastic lymphoma kinase (ALK) was first identified in 1994 with the discovery
      that the gene encoding for this kinase was involved in the t(2;5)(p23;q35)
      chromosomal translocation observed in a subset of anaplastic large cell lymphoma
      (ALCL). The NPM-ALK fusion protein generated by this translocation is a
      constitutively active tyrosine kinase, and much research has focused on
      characterizing the signalling pathways and cellular activities this oncoprotein
      regulates in ALCL. We now know about the existence of nearly 20 distinct ALK
      translocation partners, and the fusion proteins resulting from these
      translocations play a critical role in the pathogenesis of a variety of cancers
      including subsets of large B-cell lymphomas, nonsmall cell lung carcinomas, and
      inflammatory myofibroblastic tumours. Moreover, the inhibition of ALK has been
      shown to be an effective treatment strategy in some of these malignancies. In
      this paper we will highlight malignancies where ALK translocations have been
      identified and discuss why ALK fusion proteins are constitutively active tyrosine
      kinases. Finally, using ALCL as an example, we will examine three key signalling
      pathways activated by NPM-ALK that contribute to proliferation and survival in
      ALCL.

PMID- 22852080
TI  - DNA methylation, histone modifications, and signal transduction pathways: a close
      relationship in malignant gliomas pathophysiology.
AB  - Gliomas are the most common type of primary brain tumor. Although tremendous
      progress has been achieved in the recent years in the diagnosis and treatment,
      its molecular etiology remains unknown. In this regard, epigenetics represents a
      new approach to study the mechanisms that control gene expression and function
      without changing the sequence of the genome. In the present paper we describe the
      main findings about the alterations of cell signaling pathways in the most
      aggressive glioma in the adult population, namely, glioblastoma, in which
      epigenetic mechanisms and the emerging role of cancer stem cell play a crucial
      function in the development of new biomarkers for its detection and prognosis and
      the corresponding development of new pharmacological strategies.

PMID- 22852082
TI  - Functional MRI examination of visual pathways in patients with unilateral optic
      neuritis.
AB  - The relations between brain areas involved in vision were explored in 8 patients
      with unilateral acute optic neuritis using functional magnetic resonance imaging
      (fMRI) and diffusion tensor imaging (DTI). In all patients monocular stimulation
      of affected and unaffected eye elicited significantly different activation foci
      in the primary visual cortex (V1), whereas the foci evoked in the middle temporal
      visual area (area V5) were similar in size and in delay of blood-oxygen-level
      dependent response. DTI analysis documented lower white matter anisotropy values
      and reduced fibre reconstruction in the affected compared with the unaffected
      optic nerves. The preserved activation of area V5 observed in all our patients is
      an interesting finding that suggests the notion of a different sensitivity of the
      optic pathways to inflammatory changes.

PMID- 22852081
TI  - Dysregulation of the autophagy-endolysosomal system in amyotrophic lateral
      sclerosis and related motor neuron diseases.
AB  - Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of incurable motor
      neuron diseases (MNDs) characterized by a selective loss of upper and lower motor
      neurons in the brain and spinal cord. Most cases of ALS are sporadic, while
      approximately 5-10% cases are familial. More than 16 causative genes for ALS/MNDs
      have been identified and their underlying pathogenesis, including oxidative
      stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction,
      neural inflammation, protein misfolding and accumulation, dysfunctional
      intracellular trafficking, abnormal RNA processing, and noncell-autonomous
      damage, has begun to emerge. It is currently believed that a complex interplay of
      multiple toxicity pathways is implicated in disease onset and progression. Among
      such mechanisms, ones that are associated with disturbances of protein
      homeostasis, the ubiquitin-proteasome system and autophagy, have recently been
      highlighted. Although it remains to be determined whether disease-associated
      protein aggregates have a toxic or protective role in the pathogenesis, the
      formation of them results from the imbalance between generation and degradation
      of misfolded proteins within neuronal cells. In this paper, we focus on the
      autophagy-lysosomal and endocytic degradation systems and implication of their
      dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway
      could be a major target for the development of therapeutic agents for ALS/MNDs.

PMID- 22852083
TI  - Care for patients with type 2 diabetes in a random sample of community family
      practices in ontario, Canada.
AB  - Objective. Diabetes care is an important part of family practice. Previous work
      indicates that diabetes management is variable. This study aimed to examine
      diabetes care according to best practices in one part of Ontario. Design and
      Participants. A retrospective chart audit of 96 charts from 18 physicians was
      conducted to examine charts regarding diabetes care during a one-year period.
      Setting. Grimsby, Ontario. Main Outcome Measures. Glycemic screening, control and
      management strategies, documentation and counselling for lifestyle habits,
      prevalence of comorbidities, screening for hypertension, hyperlipidemia, and use
      of appropriate recommended preventive medications in the charts were examined.
      Results. Mean A1c was within target (less than or equal to 7.00) in 76% of
      patients (ICC = -0.02), at least 4 readings per annum were taken in 75% of
      patients (ICC = 0.006). Nearly 2/3 of patients had been counselled about diet,
      more than 1/2 on exercise, and nearly all (90%) were on medication. Nearly all
      patients had a documented blood pressure reading and lipid profile. Over half
      (60%) had a record of their weight and/or BMI. Conclusion. Although room for
      improvement exists, diabetes targets were mainly reached according to recognized
      best practices, in keeping with international data on attainment of diabetes
      targets.

PMID- 22852084
TI  - Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome
      Mediated Delivery of Therapeutic Proteasome.
AB  - Mesenchymal stem cells (MSCs) are used in many of the current stem cell-based
      clinical trials and their therapeutic efficacy has increasingly been attributed
      to secretion of paracrine factors. We have previously demonstrated that a
      therapeutic constituent of this secretion is exosome, a secreted bilipid membrane
      vesicle of ~50-100 nm with a complex cargo that is readily internalized by H9C2
      cardiomyocytes. It reduces infarct size in a mouse model of myocardial
      ischemia/reperfusion (MI/R) injury. We postulate that this therapeutic efficacy
      is derived from the synergy of a select permutation of individual exosome
      components. To identify protein candidates in this permutation, the proteome was
      profiled and here we identified 20S proteasome as a protein candidate. Mass
      spectrometry analysis detected all seven alpha and seven beta chains of the 20S
      proteasome, and also the three beta subunits of "immunoproteasome" with a very
      high confidence level. We demonstrated that a functional proteasome copurified
      with MSC exosomes with a density of 1.10-1.18 g/mL, and its presence correlated
      with a modest but significant reduction in oligomerized protein in a mouse model
      of myocardial infarction. Circulating proteasomes in human blood also copurified
      with exosomes. Therefore, 20S proteasome is a candidate exosome protein that
      could synergize with other constituents to ameliorate tissue damage.

PMID- 22852085
TI  - Mood Disorders among Older Adults Participating in Individual and Group Active
      Environments: "Me" versus "Us," or Both?
AB  - Involvement in physical activity is associated with improved mental health
      including better social skills, coping mechanisms, and lower rates of depression.
      However, evidence on whether group or individual active environments better
      facilitate these benefits remains inconsistent. This cross-sectional cohort study
      examined the mental health reports of older adults (aged 50+) in relation to
      participation in group or individual active environments. Logistic multivariate
      regression analyses were conducted on the Canadian Community Health Survey (cycle
      4.1, 2007-2008, n = 44, 057). Results illustrated that those active in both group
      and individual environments were 59% less likely to have a mood disorder than
      those who were not participating in either (P < 0.001). Also, those active in
      both environments were 31% less likely to have a mood disorder than those active
      in an individual environment (P < 0.001). Participating in only group or only
      individual environments had a similar effect compared to individuals not active
      in any environments for reducing rates of reported mood disorders (22% and 28%,
      resp.). However, the findings related to only group environments were not
      significant. These findings reveal that participating in both group and
      individual physical activities may have important implications for maintaining
      older adults' mental health status.

PMID- 22852087
TI  - Determining the needs, priorities, and desired rehabilitation outcomes of young
      adults who have had a stroke.
AB  - Background. Guidelines state that young adults' (aged 18-55 years) rehabilitation
      needs and priorities following stroke are different from older adults'. However,
      there is a lack of evidence regarding young adults' perspectives of their needs
      and priorities. Aim. To gain an understanding of young adults' experience of
      stroke and associated rehabilitation needs, priorities, and desired outcomes.
      Methods. A qualitative approach was adopted, based on the phenomenology of
      Merleau-Ponty. Longitudinal data were gathered using unstructured interviews and
      analysed using phenomenological reduction. Results. Ten young adults took part in
      up to four interviews over two years. An overarching theme, Embodied
      Disorientation, and three subthemes: Mortal Body, Situated Body, and Embodied
      Perception of Difference, described the young adults' experience. A subsequent
      iterative process enabled tabulation of patient-centred rehabilitation needs,
      priorities, and outcomes. Conclusion. Rehabilitation professionals can use the
      evidence-based outcomes table to work with young adults to develop meaningful
      patient-centred goals and select appropriate interventions which align with
      identified needs and outcomes throughout the stroke recovery trajectory.

PMID- 22852086
TI  - Mitotic Kinases and p53 Signaling.
AB  - Mitosis is tightly regulated and any errors in this process often lead to
      aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic
      kinases is significantly associated with improper cell division and aneuploidy.
      Because of their importance during mitosis and the relevance to cancer, mitotic
      kinase signaling has been extensively studied over the past few decades and, as a
      result, several mitotic kinase inhibitors have been developed. Despite promising
      preclinical results, targeting mitotic kinases for cancer therapy faces numerous
      challenges, including safety and patient selection issues. Therefore, there is an
      urgent need to better understand the molecular mechanisms underlying mitotic
      kinase signaling and its interactive network. Increasing evidence suggests that
      tumor suppressor p53 functions at the center of the mitotic kinase signaling
      network. In response to mitotic spindle damage, multiple mitotic kinases
      phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53
      can also regulate the expression and function of mitotic kinases, suggesting the
      existence of a network of mutual regulation, which can be positive or negative,
      between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory
      network will provide knowledge to overcome current limitations of targeting
      mitotic kinases and further improve the results of targeted therapy.

PMID- 22852088
TI  - Lineage switching in acute leukemias: a consequence of stem cell plasticity?
AB  - Acute leukemias are the most common cancer in childhood and characterized by the
      uncontrolled production of hematopoietic precursor cells of the lymphoid or
      myeloid series within the bone marrow. Even when a relatively high efficiency of
      therapeutic agents has increased the overall survival rates in the last years,
      factors such as cell lineage switching and the rise of mixed lineages at relapses
      often change the prognosis of the illness. During lineage switching, conversions
      from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The
      central mechanisms involved in these phenomena remain undefined, but recent
      studies suggest that lineage commitment of plastic hematopoietic progenitors may
      be multidirectional and reversible upon specific signals provided by both
      intrinsic and environmental cues. In this paper, we focus on the current
      knowledge about cell heterogeneity and the lineage switch resulting from leukemic
      cells plasticity. A number of hypothetical mechanisms that may inspire changes in
      cell fate decisions are highlighted. Understanding the plasticity of leukemia
      initiating cells might be fundamental to unravel the pathogenesis of lineage
      switch in acute leukemias and will illuminate the importance of a flexible
      hematopoietic development.

PMID- 22852090
TI  - Consumer satisfaction and efficacy of the hangover cure after-effect((c)).
AB  - A consumer satisfaction study was conducted to examine the effectiveness on
      hangover of After-Effect((c)), a new food supplement dedicated to improve well
      being after an occasion of alcohol consumption. N = 113 persons were invited to
      participate in a home-based open label study to test the effectiveness of After
      Effect((c)). On a night when they intended to consume alcohol, three pills were
      taken before alcohol consumption and two pills afterwards, before going to bed.
      The following day, participants completed a survey on the amount of alcohol
      consumed, hangover symptom severity, and satisfaction of the product. N = 103
      participants completed the study. 88% of participants reported After-Effect((c))
      to be effective in reducing alcohol hangover. After-Effect((c)) significantly
      improved overall hangover severity, and all individual hangover symptoms, except
      for palpitations. In addition, a significant reduction (P = 0.0001) in the
      severity score on concentration problems was reported when using After
      Effect((c)). No gender differences were observed, and there was no relationship
      with the number of alcoholic drinks that were consumed. Consumers were satisfied
      with the product. In conclusion, consumer satisfaction and hangover severity
      scores suggest that After-Effect((c)) may be effective in reducing alcohol
      hangover. However, controlled, double-blind clinical trials should confirm these
      findings.

PMID- 22852089
TI  - Mechanistic Roles of Noncoding RNAs in Lung Cancer Biology and Their Clinical
      Implications.
AB  - Lung cancer biology has traditionally focused on genomic and epigenomic
      deregulation of protein-coding genes to identify oncogenes and tumor suppressors
      diagnostic and therapeutic targets. Another important layer of cancer biology has
      emerged in the form of noncoding RNAs (ncRNAs), which are major regulators of key
      cellular processes such as proliferation, RNA splicing, gene regulation, and
      apoptosis. In the past decade, microRNAs (miRNAs) have moved to the forefront of
      ncRNA cancer research, while the role of long noncoding RNAs (lncRNAs) is
      emerging. Here we review the mechanisms by which miRNAs and lncRNAs are
      deregulated in lung cancer, the technologies that can be applied to detect such
      alterations, and the clinical potential of these RNA species. An improved
      comprehension of lung cancer biology will come through the understanding of the
      interplay between deregulation of non-coding RNAs, the protein-coding genes they
      regulate, and how these interactions influence cellular networks and signalling
      pathways.

PMID- 22852091
TI  - Comparative evaluation of two types of immediately loaded implants using
      biomechanical and histomorphometric tests: an animal case study.
AB  - Introduction. In order to minimize the required time to regain esthetic and
      function, immediately loaded implants were suggested. The aim of this study was
      to comparatively evaluate the Nisastan and XIve implants using biomechanical and
      histomorphometric tests. Materials and Methods. In this experimental study, 6
      Nisastan one-piece immediately loaded screw type implant (OPILS) and 6 Xive
      implants with 3.4 mm diameter and 11 mm long were used. The implants were
      immediately loaded with temporary coating. After three months, the torque
      required to break bone-implant contact was measured and was recorded. All
      implants were extracted with surrounding bone and histologically were evaluated.
      The data were inputted into the SPSS 11.5 to run student T-test statistical
      analyses (alpha = 0.05). Results. The success rates of both types of implants was
      100%, and none of them failed due to mobility or bone loss. The mean removal
      torque value (RTV) was 142.08 and 40 N/Cm for Xive and Nisastan implants,
      respectively, and their RTVs showed a significant difference between two
      mentioned implants (P = 0.004). None of the histomorphometric values showed
      significant differences between the two implants (P > 0.05). Discussion. both
      systems have the capability to induce osseointegration under immediate loads but
      that Xive implants showed higher capability for bone contact.

PMID- 22852092
TI  - Early detection of maternal risk for preeclampsia.
AB  - Preeclampsia is one of the leading causes of maternal and fetal morbidity and
      mortality. New molecular insights offer new possibilities of early diagnosis of
      elevated maternal risk. Maternal risk factors, biophysical parameters like
      Doppler examination of the uterine arteries and biochemical parameters allow
      early risk calculation. Preventive and effective therapeutic agents like
      acetylsalicylacid can be started in the early second trimester. This article
      reviews the diagnostic possibilities of early risk calculation to detect women
      having high risk for preeclampsia and the potential benefits for them, the
      offspring and health care systems. We provide risk calculation for preeclampsia
      as an important and sensible part of first trimester screening.

PMID- 22852093
TI  - Urinary bisphenol a levels and measures of obesity: results from the national
      health and nutrition examination survey 2003-2008.
AB  - Bisphenol A (BPA) is a widely used chemical. We examined the association between
      urinary BPA levels and obesity in the National Health and Nutritional Examination
      Survey (NHANES) 2003-2008. The main outcome of interest was obesity defined as
      (1) body mass index (BMI) >= 30 Kg/m(2) and (2) waist circumference (WC) >= 102
      cm in men and >= 88 cm in women. Urinary BPA levels were examined in quartiles.
      Overall, we observed a positive association between increasing levels of urinary
      BPA and both measures of obesity, independent of potential confounding factors
      including, smoking, alcohol consumption, and serum cholesterol levels. Compared
      to quartile 1 (referent), the multivariate-adjusted odds ratio (95% confidence
      interval) associated with quartile 4 for BMI-based obesity was 1.69 (1.30-2.20);
      P-trend < 0.0001 and for WC-based obesity was 1.59 (1.21-2.09); P-trend = 0.0009.
      This association between BPA and both measures of obesity was consistently
      present across gender and race-ethnic groups (all P-trend < 0.05). Elevated
      levels of urinary BPA are associated with measures of obesity independent of
      traditional risk factors. This association is consistently present across gender
      and race-ethnic groups. Future prospective studies are needed to confirm or
      disprove this finding.

PMID- 22852094
TI  - Using a socioecological framework to understand the career choices of single- and
      double-degree nursing students and double-degree graduates.
AB  - Untested changes in nursing education in Australia, such as the introduction of
      double degrees in nursing, necessitate a new research approach to study nursing
      career pathways. A review of the literature on past and present career choice
      theories demonstrates these are inadequate to gain an understanding of
      contemporary nursing students' career choices. With the present worldwide
      shortage of nurses, an understanding of career choice becomes a critical
      component of recruitment and retention strategies. The purpose of this paper is
      to demonstrate how an ecological system approach based on Bronfenbrenner's theory
      of human development can be used to understand and examine the influences
      affecting nursing students' and graduates' career development and career choices.
      Bronfenbrenner's socioecological model was adapted to propose a new Nursing
      Career Development Framework as a way of conceptualizing the career development
      of nursing students undertaking traditional bachelor of nursing and
      nontraditional double-degree nursing programs. This Framework is then applied to
      a study of undergraduate nurses' career decision making, using a sequential
      explanatory mixed method study. The paper demonstrates the relevance of this
      approach for addressing challenges associated with nursing recruitment,
      education, and career choice.

PMID- 22852095
TI  - Cognition, behavior, and respiratory function in amyotrophic lateral sclerosis.
AB  - Objective. To examine the relationship between respiratory functioning and
      neuropsychological performance, mood, and frontal-lobe-mediated behaviors in ALS
      patients. Methods. Forty-four patients with probable or definite ALS (El Escorial
      criteria) completed comprehensive pulmonary and neuropsychological assessments as
      part of their baseline neurological evaluation. Based on their full vital
      respiratory capacity, 24 and 20 patients were classified as having impaired or
      intact respiration, respectively. Results. Comparable demographic
      characteristics, neuropsychological performance, and self-reported mood symptoms
      were found between ALS patients with intact versus impaired respiration. However,
      more respiratory-impaired patients were reported by their caregivers as having
      clinically significant impairments in frontal-lobe-mediated behaviors.
      Nevertheless, declines in behavior were evidenced from pre- to post-ALS symptom
      onset for both respiratory groups, and exploratory analyses revealed greater
      executive functioning deficits in patients with bulbar versus limb onset as well
      as respiratory-impaired patients not receiving pulmonary interventions versus
      those utilizing such interventions at the time of testing. Conclusions. Results
      suggest that the respiratory insufficiency of ALS patients may potentially
      produce irreversible deficits in executive functioning; yet once treated,
      impairments in more basic cognitive abilities may be less evident.

PMID- 22852096
TI  - Comparison of gene expression profiling in sarcomas and mesenchymal stem cells
      identifies tumorigenic pathways in chemically induced rat sarcoma model.
AB  - Mesenchymal stem cells (MSCs) are believed to be the cell of origin for most
      sarcomas including osteosarcoma and malignant fibrous histiocytoma (MFH/UPS). To
      identify the signaling pathways involved in sarcoma pathogenesis, we compared
      gene expression profiles in rat osteosarcoma and MFH cells with those in
      syngeneic rat MSCs. Analysis of genes that characterize MSCs such as CD44, CD105,
      CD73, and CD90 showed higher expression in MSCs compared to sarcomas. Pathways
      involved in focal and cell adhesion, cytokine-cytokine receptors, extracellular
      matrix receptors, chemokines, and Wnt signaling were down-regulated in both
      sarcomas. Meanwhile, DNA replication, cell cycle, mismatch repair, Hedgehog
      signaling, and metabolic pathways were upregulated in both sarcomas.
      Downregulation of p21(Cip1) and higher expression of CDK4-cyclinD1 and CDK2
      cyclinE could accelerate cell cycle in sarcomas. The current study indicated that
      these rat sarcomas could be a good model for their human counterparts and will
      provide the further insights into the molecular pathways and mechanisms involved
      in sarcoma pathogenesis.

PMID- 22852097
TI  - Matrix Metalloproteinases and Bladder Cancer: What is New?
AB  - Urothelial bladder cancer represents a heterogeneous disease with divergent
      pathways of tumorigenesis. Tumor invasion and progression are a multifactorial
      process promoted by microenvironmental changes that include overexpression of
      matrix metalloproteinases (MMPs). Recent data clearly challenge the classic dogma
      that MMPs promote metastasis only by modulating the remodeling of extracellular
      matrix. Indeed, MMPs have also been attributed as an impact on tumor cell
      behavior in vivo as a consequence of their ability to cleave growth factors, cell
      surface receptors, cell adhesion molecules, and chemokines/cytokines. Levels of
      the different MMPs can be measured in several sample types, including tissue,
      blood (serum and plasma), and urine, and using different methodologies, such as
      immunohistochemistry, real-time PCR, western and northern blot analyses, enzyme
      linked immunosorbent assay, and zymography. Several MMPs have been identified as
      having potential diagnostic or prognostic utility, whether alone or in
      combination with cytology. Although MMP inhibitors have shown limited efficacy,
      advances in the understanding of the complex physiologic and pathologic roles of
      MMPs might permit the development of new MMP-specific and tumor-specific
      therapies. In this paper we update the understanding of MMPs based on a
      systematic PubMed search encompassing papers published up to December 2011.

PMID- 22852100
TI  - Osmotic drug delivery system as a part of modified release dosage form.
AB  - Conventional drug delivery systems are known to provide an immediate release of
      drug, in which one can not control the release of the drug and can not maintain
      effective concentration at the target site for longer time. Controlled drug
      delivery systems offer spatial control over the drug release. Osmotic pumps are
      most promising systems for controlled drug delivery. These systems are used for
      both oral administration and implantation. Osmotic pumps consist of an inner core
      containing drug and osmogens, coated with a semipermeable membrane. As the core
      absorbs water, it expands in volume, which pushes the drug solution out through
      the delivery ports. Osmotic pumps release drug at a rate that is independent of
      the pH and hydrodynamics of the dissolution medium. The historical development of
      osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper
      pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push
      pull system. Recent advances include development of the controlled porosity
      osmotic pump, and systems based on asymmetric membranes. This paper highlights
      the principle of osmosis, materials used for fabrication of pumps, types of
      pumps, advantages, disadvantages, and marketed products of this system.

PMID- 22852101
TI  - Fine needle aspiration cytology of cysticercosis-a case report.
AB  - Cysticercosis, caused by cysticercus cellulosae, the larval form of Taenia
      solium, is potentially a dangerous systemic disease with variable clinical
      manifestations. The disease most commonly involves subcutaneous and muscle
      tissues, followed by the eye and brain. Cysticercosis can be diagnosed by various
      radiologic means or by serology, both of which, however, are not definitive.
      Biopsy and histologic examination containing the cysticerci is the most
      definitive method of diagnosis. We report a case of cysticercosis in a 27-year
      old male patient, who presented with a subcutaneous swelling in the back which
      was diagnosed on fine needle aspiration cytology (FNAC).

PMID- 22852098
TI  - Visual cortex plasticity: a complex interplay of genetic and environmental
      influences.
AB  - The central nervous system architecture is highly dynamic and continuously
      modified by sensory experience through processes of neuronal plasticity.
      Plasticity is achieved by a complex interplay of environmental influences and
      physiological mechanisms that ultimately activate intracellular signal
      transduction pathways regulating gene expression. In addition to the remarkable
      variety of transcription factors and their combinatorial interaction at specific
      gene promoters, epigenetic mechanisms that regulate transcription have emerged as
      conserved processes by which the nervous system accomplishes the induction of
      plasticity. Experience-dependent changes of DNA methylation patterns and histone
      posttranslational modifications are, in fact, recruited as targets of plasticity
      associated signal transduction mechanisms. Here, we shall concentrate on
      structural and functional consequences of early sensory deprivation in the visual
      system and discuss how intracellular signal transduction pathways associated with
      experience regulate changes of chromatin structure and gene expression patterns
      that underlie these plastic phenomena. Recent experimental evidence for
      mechanisms of cross-modal plasticity following congenital or acquired sensory
      deprivation both in human and animal models will be considered as well. We shall
      also review different experimental strategies that can be used to achieve the
      recovery of sensory functions after long-term deprivation in humans.

PMID- 22852099
TI  - Lessons learned from the transgenic Huntington's disease rats.
AB  - Huntington's disease (HD) is a fatal inherited disorder leading to selective
      neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment
      to slow down or to stop the disease. There is also no therapy to effectively
      reduce the symptoms. In the investigation of novel therapies, different animal
      models of Huntington's disease, varying from insects to nonhuman primates, have
      been created and used. Few years ago, the first transgenic rat model of HD,
      carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control
      of the native rat huntingtin promoter, was introduced. We have been using this
      animal model in our research and review here our experience with the behavioural,
      neurophysiological, and histopathological phenotype of the transgenic
      Huntington's disease rats with relevant literature.

PMID- 22852102
TI  - Secondary vesical calculus resulting from migration of an intrauterine
      contraceptive device.
AB  - Intrauterine contraceptive device (IUCD) is the commonest form of contraception
      used in view of less systemic side effects. However, there are a multitude of
      local complications caused by it. Of all the local complications described,
      migration of the device into adjacent organs is the most morbid of all
      complications. A patient presenting with history of loss or disappearance of the
      intrauterine contraceptive device accompanied by urinary symptoms should raise
      the doubt of a migrated device with the formation of a secondary calculus. This
      prompts further radiological investigations and merits surgical intervention
      either endourologically or by open surgery depending upon the merits of the case.
      A case report elucidating this fact is presented.

PMID- 22852103
TI  - Chylothorax from Bilateral Primary Burkitt's Lymphoma of the Ovaries: A Case
      Report.
AB  - We present a case of bilateral ovarian Burkitt's lymphoma is an 18-year old.
      Diagnosis was made at histology of specimens obtained after an exploratory
      (diagnostic) laparotomy. Disease was advanced at presentation and complicated
      with both chylothorax and chylous ascites. Response to chemotherapy though
      dramatic was short lived. This underscores the need for high index of suspicion
      amongst clinicians. The availability of affordable less traumatic diagnostic
      procedures like laparoscopy and computerized tomography scans with facilities for
      guided biopsies in resource-poor settings can fast track diagnosis and hence
      treatment.

PMID- 22852104
TI  - HELLP Syndrome Complicated with Postpartum Subcapsular Ruptured Liver Hematoma
      and Purtscher-Like Retinopathy.
AB  - Purtscher's retinopathy is usually associated with trauma, acute pancreatitis,
      vasculitis, lupus, and bone fractures. It was rarely described postpartum in
      patients with preeclampsia as well as associated with HELLP syndrome. We present
      a case of a multiparous patient aged 44 with severe preeclampsia and postpartum
      HELLP syndrome complicated with Purtscher-like retinopathy and large ruptured
      subcapsular liver hematoma that required emergency abdominal surgery after
      premature delivery of a dead fetus. Postsurgical outcome was favorable regarding
      both liver function and visual acuity.

PMID- 22852105
TI  - Tuberculosis in Goats and Sheep in Afar Pastoral Region of Ethiopia and Isolation
      of Mycobacterium tuberculosis from Goat.
AB  - A cross sectional study was conducted on 2231 small ruminants in four districts
      of the Afar Pastoral Region of Ethiopia to investigate the epidemiology of
      tuberculosis in goats and sheep using comparative intradermal tuberculin skin
      test, postmortem examination, mycobacteriological culture and molecular typing
      methods. The overall animal prevalence of TB in small ruminants was 0.5% (95% CI:
      0.2%-0.7%) at >=4 mm and 3.8% (95% CI: 3%-4.7%) at cutoff >=2 mm. The herd
      prevalence was 20% (95% CI: 12-28%) and 47% (95% CI: 37-56%) at >=4 mm and >=2 mm
      cut-off points, respectively. The overall animal prevalence of Mycobacterium
      avium complex infection was 2.8% (95% CI: 2.1-3.5%) and 6.8% (95% CI: 5.8-7.9%)
      at >=4 mm and >=2 mm cut-off points, respectively. Mycobacteriological culture
      and molecular characterization of isolates from tissue lesions of tuberculin
      reactor goats resulted in isolation of Mycobacterium tuberculosis (SIT149) and
      non-tuberculosis mycobacteria as causative agents of tuberculosis and
      tuberculosis-like diseases in goats, respectively. The isolation of Mycobacterium
      tuberculosis in goat suggests a potential transmission of the causative agent
      from human and warrants further investigation in the role of small ruminants in
      epidemiology of human tuberculosis in the region.

PMID- 22852106
TI  - Note from the editor.

PMID- 22852107
TI  - Reproducibility, validity, and responsiveness of cell counts in blown nasal
      secretions.
AB  - Cell counts in nasal secretions are not used in routine clinical practice to
      decide on anti-inflammatory or antimicrobial therapy. This study investigated the
      reproducibility, reliability (validity), and responsiveness of cell counts in
      blown nasal secretions with a view to implementing this in routine clinical
      practice. Nasal secretions were obtained from 19 subjects with allergic rhinitis
      on 3 days in random order (each separated by 1-2 days) by spontaneously blowing
      their noses (on 2 days) and by a nasal lavage by the modified Grunberg method on
      the 3rd day. Total and differential cell counts were performed after dispersing
      the solutions with dithiothreitol as described previously. At the end of the
      study, subjects had 1 week of open label treatment with nasal corticosteroids if
      they had nasal eosinophilia or an antibiotic if they had nasal neutrophilia. If
      the cell counts were normal, they were not treated. The proportion of eosinophil
      (%) was highly reproducible (intraclass correlation coefficient [ICC], 0.93), and
      the total cell count (*106/g) and the proportion of neutrophil (%) were modestly
      reproducible in blown nasal secretions (ICC, 0.46 and 0.55, respectively). The
      total cell count was consistently and significantly higher in the blown nasal
      secretions. The proportion of eosinophils (R(s) = 0.4; p < 0.05) and neutrophils
      (R(s) = 0.6; p < 0.05) showed modest correlation in the two types of samples. The
      responsiveness index for eosinophil count was 4.0 and for neutrophil count was
      1.5. Total and differential cell counts can be reliably and reproducibly obtained
      from spontaneously blown nasal secretions. The cell counts are responsive to
      treatment and can help identify allergic and infective rhinosinusitis and guide
      therapy and are easy to implement in routine clinical practice.

PMID- 22852108
TI  - Sinonasal risk factors for the development of invasive fungal sinusitis in
      hematological patients: Are they important?
AB  - Invasive fungal sinusitis (IFS) is a highly aggressive infection that can affect
      hematologic patients. The classically described general risk factors, however, do
      not fully explain the development of IFS in a small percentage of cases. This
      study examined the impact of anatomic sinonasal factors and environmental factors
      on the development of IFS in high-risk patients. Medical records and computed
      tomography (CT) scans of patients admitted to our institution who were at high
      risk of developing IFS were retrospectively reviewed. Twenty-seven patients of
      797 fulfilled the inclusion criteria. Patients affected by IFS were compared with
      patients not affected to identify possible sinonasal and environmental risk
      factors of IFS. Seven patients were excluded because of the lack of adequate
      radiological images. Six of the 20 eligible patients were assigned to the study
      group of patients affected by IFS and the remaining 14 patients were assigned to
      the control group. All but one case developed the infection during the summer
      with a significantly higher mean environmental temperature (p = 0.002). Anatomic
      nasal alterations were found in all patients affected by IFS and were
      significantly more frequent than in the control group (p = 0.014). It would be
      advisable to have patients with hematologic risk factors of IFS, especially
      during the summer period, undergo endoscopic nasal assessment. Furthermore, a CT
      finding of anatomic nasal alterations, such as anterior nasal septum deviation
      causing nasal obstruction, should increase the suspicion of IFS in case of the
      occurrence of nasal symptoms.

PMID- 22852109
TI  - Is routine nasoendoscopy warranted in epistaxis patients after removal of nasal
      packing?
AB  - Fiberoptic nasoendoscopy (FNE) is a powerful investigative tool in ear, nose, and
      throat practice in which its use in the management of epistaxis is varied among
      clinicians. The practice of assessing the nasal cavity after removal of nasal
      packs is common but its usefulness has not been evaluated. Therefore, we assessed
      the benefits of routine FNE after removal of nasal packs in epistaxis patients.
      Our study was performed retrospectively involving 62 adult patients admitted over
      a 6-month period between 2005 and 2006. Data regarding the emergent management of
      epistaxis cases on presentation, the use of FNE, and the final diagnosis and
      outcome of each patient were specifically investigated during the study. Anterior
      rhinoscopy was performed in 27 patients at initial presentation, of whom 45%
      (10/27) had anterior bleeding points identified. FNE examination after removal of
      nasal packs in eight patients yielded evidence of a posterior bleeding point in
      only one case (12.5%). Of those patients in whom anterior rhinoscopy revealed no
      anterior bleeding point at presentation (17/27), 12 patients went on to have FNE
      after removal of their nasal packs, and of these, 33% (4/12) of patients were
      found to have a posterior bleeding vessel. Overall, FNE was performed in 24
      patients, of whom only 1 (1/24) had an active posterior bleeding vessel needing
      nasal repacking. Four patients (4/24) had prominent posterior vessels that
      required no intervention, 1 patient (1/24) had new pathology identified, and in
      the remaining 18 cases (18/24), FNE yielded no additional information to modify
      management. The routine performance of FNE in all epistaxis patients after pack
      removal does not appear to convey any additional benefit. We advocate the use of
      FNE when anterior bleeding has been excluded or bleeding is persistent and that
      careful nasal examination by anterior rhinoscopy should be the cornerstone of
      assessment.

PMID- 22852110
TI  - Expression of bone morphogenic protein in sinonasal inverted papilloma with new
      bone formation.
AB  - Inverted papilloma (IP) is a common benign tumor in the nose and sinus.
      Osteogenesis in sinonasal IP is extremely rare; to date, only five cases of IP
      with new bone formation appear in the literature. In addition, the mechanism of
      osteogenesis in IP remains unclear. Here, we describe three cases of IP with new
      bone formation and an investigation into a possible role for bone morphogenic
      protein (BMP) in osteogenesis. Of three patients with sinonasal IP with new bone
      formation, two were treated by endoscopic sinus surgery and one was followed up
      with watchful waiting. Tumor tissues were subjected to immunohistochemistry to
      detect BMP expression. The patients were successfully treated surgically and
      showed no evidence of recurrence postoperatively. Follow-up examination is
      ongoing. Immunohistochemically, the tumors expressed BMP-4 but not BMP-2 or BMP
      7. ESS could be successfully used to achieve complete removal of the sinonasal
      IPs with new bone formation. BMP-4 might be associated with new bone formation in
      the tumor.

PMID- 22852111
TI  - Indoor fungal concentration in the homes of allergic/asthmatic children in Delhi,
      India.
AB  - Allergy to fungi has been linked to a wide range of illnesses, including rhinitis
      and asthma. Therefore, exposure to fungi in home environment is an important
      factor for fungal allergy. The present study was aimed to investigate types of
      airborne fungi inside and outside the homes of asthmatic children and control
      subjects (nonasthmatic children). The dominant fungi were evaluated for their
      quantitative distribution and seasonal variation. The air samples were collected
      from indoors and immediate outdoors of 77 selected homes of children suffering
      from bronchial asthma/allergic rhinitis using Andersen volumetric air sampler.
      The isolated fungal genera/species were identified using reference literature,
      and statistical analysis of the dominant fungi was performed to study the
      difference in fungal concentration between indoor and immediate outdoor sites as
      well as in between different seasons. A total of 4423 air samples were collected
      from two indoor and immediate outdoor sites in a 1-year survey of 77 homes. This
      resulted in the isolation of an average of 110,091 and 107,070 fungal colonies
      per metric cube of air from indoor and outdoor sites, respectively. A total of 68
      different molds were identified. Different species of Aspergillus, Alternaria,
      Cladosporium, and Penicillium were found to be the most prevalent fungi in Delhi
      homes, which constituted 88.6% of the total colonies indoors. Highest
      concentration was registered in autumn and winter months. Total as well as
      dominant fungi displayed statistically significant differences among the four
      seasons (p < 0.001). The largest number of isolations were the species of
      Aspergillus (>40% to total colony-forming units in indoors as well as outdoors)
      followed by Cladosporium spp. Annual concentration of Aspergillus spp. was
      significantly higher (p < 0.05) inside the homes when compared with outdoors.
      Most of the fungi also occurred at a significantly higher (p < 0.001) rate inside
      the homes when compared with immediate outdoors. Asthmatic children in Delhi are
      exposed to a substantial concentration of mold inside their homes as well as
      immediate outdoor air. The considerable seasonal distributions of fungi provide
      valuable data for investigation of the role of fungal exposure as a risk for
      respiratory disorders among patients suffering from allergy or asthma in Delhi.

PMID- 22852112
TI  - Assessment of synthetic glucocorticoids in asthmatic sputum.
AB  - Nonadherence with anti-inflammatory treatment is a frequent cause of continued
      symptoms in asthmatic patients. Clinical assessments including patient-reported
      medication administration may provide the asthma specialist incomplete
      information regarding actual adherence to anti-inflammatory medications. The
      objective of this report was to describe the first case where adherence to
      inhaled asthma therapy was assessed by direct analysis of glucocorticoids in
      induced sputum. The patient's blood, urine, and sputum were tested for synthetic
      corticosteroids using mass spectrometry. To evaluate a clinical suspicion of poor
      adherence, sputum, urine, and blood were used to assess for current compliance to
      medication use. We report a case where asthma specialists attributed poorly
      controlled asthma to nonadherence to medical therapy. After modification of the
      medical regimen, adherence with oral and inhaled steroids was assessed-via
      examination of the urine, blood, and sputum. Direct analysis of glucocorticoids
      in sputum is feasible and in theory could provide a novel tool to document
      current medication adherence. Concomitant assessment of glucocorticoids and
      eosinophils in the same induced sputum specimen could provide insight into
      possible steroid resistance in select referral patients with difficult asthma.

PMID- 22852113
TI  - Skull base defect in a patient with ozena undergoing dacryocystorhinostomy.
AB  - Ozena, which is often used interchangeably with atrophic rhinitis or empty nose
      syndrome, is a progressive and chronically debilitating nasal disease that
      results in atrophy of the nasal mucosa, nasal crusting, fetor, and destruction of
      submucosal structures. Although the etiology is not completely understood,
      infection with Klebsiella ozaenae is widely believed to contribute to the
      destructive changes. We present a case of a patient with ozena secondary to K.
      ozaenae with extensive destruction of bony structures of the nasal cavity
      undergoing elective dacryocystorhinostomy. An extensively thinned skull base
      secondary to the disease process resulted in an unforeseen complication in which
      the skull base was entered leading to a cerebrospinal fluid leak. Patients with
      known history of ozena or atrophic rhinitis often have extensive destruction of
      the lateral nasal wall and skull base secondary to progression of disease.
      Submucosal destruction of these bony structures mandates the need for extreme
      caution when planning on performing endoscopic intervention at or near the skull
      base. If physical examination or nasal endoscopy is suspicious for atrophic
      rhinitis or a patient has a known history of infection with K. ozaenae, we
      recommend preoperative imaging for surgical planning with careful attention to
      skull base anatomy.

PMID- 22852114
TI  - Temporal lobe abscess in a patient with isolated sphenoiditis.
AB  - A 74-year-old immunocompetent man admitted for severe retro-orbital headache was
      diagnosed with isolated sphenoiditis. At the time of scheduled surgery, the
      patient was mildly obtunded, and a head CT revealed a temporal lobe abscess. The
      patient underwent a left temporal craniectomy and a bilateral endoscopic sphenoid
      sinusotomy, which revealed gross fungal debris. The patient made a full recovery
      with resolution of abscess and sinus findings. Suspicion for intracranial
      infection should be raised in any sinus patient with neurological changes. Early
      diagnosis with imaging studies is extremely important for surgical drainage
      before permanent neurological sequelae.

PMID- 22852115
TI  - Allergic reaction to mint leads to asthma.
AB  - Respiratory and cutaneous adverse reactions to mint can result from several
      different mechanisms including IgE-mediated hypersensitivity, delayed-type
      hypersensitivity (contact dermatitis), and nonimmunologic histamine release.
      Reactions to cross-reacting plants of the Labiatae family, such as oregano and
      thyme, as well as to the chemical turpentine, may clue the clinician in on the
      diagnosis of mint allergy. Contact dermatitis can result from menthol in
      peppermint. Contact allergens have been reported in toothpastes, which often are
      mint-flavored. Allergic asthma from mint is less well-recognized. A case of a 54
      year-old woman with dyspnea on exposure to the scent of peppermint is presented
      in whom mint exposure, as seemingly innocuous as the breath of others who had
      consumed Tic Tac candies, exacerbated her underlying asthma. This case highlights
      the importance of testing with multiple alternative measures of specific IgE to
      mint, including skin testing with mint extract, and skin testing with fresh mint
      leaves. Additionally, this cases suggests that asthma can result from inhaling
      the scent of mint and gives consideration to obtaining confirmatory pre- and
      postexposure pulmonary function data by both impulse oscillometry and spirometry.

PMID- 22852116
TI  - Effects of cromolyn sodium on isolated rat's trachea.
AB  - Cromolyn sodium (cromolyn) effectively inhibits both antigen- and exercise
      induced asthma when used as an aerosol. Intranasal cromolyn is also recommended
      for preventing and treating allergic rhinitis. By inhibiting the degranulation of
      sensitized mast cells, cromolyn reduces the release of mediators that trigger
      inflammation and the allergic response. The precise pharmacologic activity of
      cromolyn has not been fully elucidated. This study evaluated the effect of
      cromolyn on isolated rat's trachea. The following assessments of cromolyn were
      performed: (1) effect on tracheal resting tension, (2) effect on contraction
      caused by 10(-6) M of methacholine as a parasympathetic mimetic, and (3) effect
      of the drug on electrically induced tracheal contractions. The results indicated
      cromolyn could inhibit electrical field stimulation-induced spike contraction
      when the preparation was increased to 10(-4)M. Adding cromolyn at doses of >=10(
      8) M did not elicit a relaxation or contraction response to 10(-6) M of
      methacholine-induced contraction. It alone had a minimal effect on the basal
      tension of the trachea as the concentration increased. This study indicates
      cromolyn had no cholinergic or anticholinergic effect and high concentrations of
      cromolyn might actually inhibit parasympathetic function of the trachea.
      Inhibiting parasympathetic function of the trachea through stabilizing the
      presynaptic nerve by cromolyn may be responsible for protecting patients against
      antigen- and exercise-induced asthma.

PMID- 22852117
TI  - Oral curcumin supplementation in patients with atopic asthma.
AB  - Oral curcumin is recognized to have anti-inflammatory properties and has been
      used by ancient traditional medicine for centuries to treat a variety of
      diseases. In vitro studies have confirmed the ability of curcumin to inhibit
      allergic inflammatory cytokine responses from lymphocytes; however, there are no
      in vivo studies of curcumin to treat inflammation associated with allergic
      asthma. This study was designed to determine the effect of oral curcumin
      supplementation on patients with stable, persistent, atopic asthma. Adult
      patients with stable, persistent asthma with evidence of allergic sensitization
      were randomized to receive 1000 mg of curcumin twice daily or placebo. Subjects
      were followed for 6 months and performed monthly spirometry (pre- and
      postbronchodilator); Asthma Control Test (ACT) scoring; and measurements for
      fractional excretion of nitric oxide (NO), serum eosinophil count, leukocyte
      count, total IgE, specific IgE to Dermatophagoides pteronyssinus (Der p) and
      Dermatophagoides farinae (Der f), use of rescue albuterol, and dose of inhaled
      corticosteroid. Nine patients were randomized into the treatment arm and six were
      randomized into the placebo group. No differential response was seen in the
      treatment and placebo groups regarding the primary end point, postbronchodilator
      forced expiratory volume in 1 second (FEV(1)). Similarly, all secondary end point
      evaluations were not significantly different. Despite in vitro evidence that
      curcumin has anti-inflammatory properties and can inhibit allergic cytokine
      responses from lymphocytes in vitro, curcumin, 1000-mg, twice daily
      supplementation did not significantly affect postbronchodilator FEV(1), ACT
      scores, use of rescue bronchodilator, dose of inhaled corticosteroid, exhaled NO,
      serum IgE, total white blood cell count specific IgE to Der p or Der f, and blood
      eosinophils in patients with persistent atopic asthma.

PMID- 22852118
TI  - Postoperative cephazolin usage is sufficient for preventing infection after
      septoplasty procedure.
AB  - The use of antibiotics in septoplasty is a common practice among most ear, nose,
      and throat doctors; however, there are few studies proving the efficacy, which is
      considered as unnecessary by some authors. The aim of this pilot study was to
      evaluate the effect of two different kinds of antimicrobial agent on efficacy and
      safety after septoplasty surgery and to show that use of cephazolin, 1.0 g,
      postoperatively, might be sufficient for preventing infection after septoplasty
      procedure. Patients were randomly divided into two groups with a simple
      randomization method. The first group of 80 patients received cephazolin, 1.0 g
      i.v., once postoperatively and the second group of 80 patients received
      amoxicillin-clavulanate orally for 7 days postoperatively (1000 mg). An early and
      late postoperative questionnaire and nasal endoscopy evaluation was performed and
      patients were followed up in the outpatient service to investigate the presence
      of complications. There was no significant difference in postoperative pain
      between groups A and B, using visual analog scale scores at the 1st postoperative
      day. There were no differences related to the amount of purulent discharge found
      at the lower margin of the inferior turbinate through nasal endoscopy performed
      on the 14th day postoperatively. There were no statistical significances among
      groups for complications rates and postoperative endoscopic evaluation.
      Septoplasties are considered potentially contaminated surgeries, and cephazolin,
      1.0 g i.v., given once postoperatively is enough to prevent potential
      complications with its easy and effective use.

PMID- 22852119
TI  - A case of uncontrolled asthma.
AB  - A 48-year-old female patient with uncontrolled severe asthma was referred to our
      hospital for anti-IgE therapy. She was suffering with persistent wheezing and
      dyspnea after a severe asthma attack that had taken place 5 months previously.
      Her asthma had not been controlled with adequate asthma treatment, including
      budesonide at 320 MUg + formoterol at 9 MUg b.i.d. combination, montelukast at 10
      mg/day, and oral steroids (30-40 mg/day of prednisolone), during this period. She
      was hospitalized for evaluation for anti-IgE therapy. Chest radiography revealed
      a left-sided hilar opacity. Fiberoptic bronchoscopy was performed and showed an
      endobronchial lesion obstructing the left lower bronchus lumen. Computed
      tomography also revealed a nodular lesion at the same location. The patient
      underwent left lower lobectomy and mediastinal lymph node dissection.
      Pathological examination concluded the diagnosis of typical carcinoid tumor.
      After surgery, her symptoms disappeared and she has had no recurrence. In
      conclusion, a diagnosis of severe asthma requires confirmation of asthma.
      Uncontrolled symptoms that linger despite aggressive therapy warrant evaluation
      to rule out other etiologies, such as a carcinoid tumor, before selecting new
      treatment options.

PMID- 22852121
TI  - Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma.
AB  - Asthma is a multifactorial disorder, primarily resulting from interactions
      between genetic and environmental factors. ADAM33 gene (located on chromosome
      20p13) has been reported to play an important role in asthma. This review article
      is intended to include all of the publications, to date, which have assessed the
      association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33
      gene in airway remodeling and their expression with asthma. A PubMed search was
      performed for studies published between 1990 and 2010. The terms "ADAM33,"
      "ADAM33 gene and asthma," and "ADAM33 gene polymorphisms" were used as search
      criteria. Based on available literature we can only speculate its role in the
      morphogenesis and functions of the lung. Fourteen studies conducted in different
      populations were found showing an association of ADAM33 gene polymorphisms with
      asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33
      gene had found association with asthma across all ethnic groups. Because higher
      expression of ADAM33 is found in the fibroblast and smooth muscle cells of the
      lung, over- or underexpression of ADAM33 gene may result in alterations in airway
      remodeling and repair processes. However, no SNP of ADAM33 gene showed
      significant associations with asthma across all ethnic groups; the causative
      polymorphism, if any, still has to be identified.

PMID- 22852122
TI  - Adult seafood allergy in the Texas Medical Center: A 13-year experience.
AB  - There is a paucity of data regarding prevalence and characteristics of adult
      seafood allergy in United States cohorts. This study was designed to determine
      the characteristics of patient-reported seafood allergy in a large allergy
      referral adult population. Retrospective analysis was performed of laboratory and
      clinical characteristics of seafood-allergic patients in three allergy clinics in
      the Texas Medical Center between January 1, 1997 and January 30, 2010. Of 5162
      patients seen in this adult allergy referral population, 159 had physician
      diagnosed seafood allergy with an average age of diagnosis of 50.2 (18-81 years)
      years. Shellfish allergy (59.1%) was more frequent than fish allergy (13.8%).
      Crustacean allergy (82.6%) was more frequent than mollusk allergy (7.2%). Shrimp
      (72.5%), crab (34.8%), and lobster (17.4%) were the most common shellfish
      allergies and tuna (28.6%), catfish (23.8%), and salmon (23.8%) were the most
      common fish allergies. One-third of seafood-allergic patients reported reactions
      to more than one seafood. Shellfish-allergic adults were more likely to
      experience respiratory symptoms than fish-allergic adults (p < 0.05). The
      likelihood of having anaphylaxis (32%) was not statistically different between
      shellfish- and fish-allergic subjects. Severe reactions were 12.9 times more
      likely to occur within the 1st hour of ingestion compared with nonsevere
      reactions (p < 0.005). The percentage of seafood allergy in this adult allergy
      referral population was 3.08%.

PMID- 22852123
TI  - Quality of life comparison in common rhinologic surgeries.
AB  - Various questionnaires are used in patients who undergo rhinologic surgeries but
      a unique comprehensive questionnaire is needed to evaluate quality of life (QOL)
      in rhinologic surgeries. The purpose of this study was to prepare a comprehensive
      questionnaire and compare QOL among four common rhinologic surgeries including
      functional endoscopic sinus surgery, septoplasty, septorhinoplasty, and
      septoplasty with turbinoplasty preoperatively and 6 months postoperatively. This
      was a prospective interventional before-and-after study. Preoperative and 6
      months postoperative evaluations were performed with a Modified Health-Related
      Quality of Life (HRQL) questionnaire designed to cover all needed QOL aspects and
      the 22-item Sino-nasal Outcome Test questionnaire to cover all needed QOL
      aspects. The Modified HRQL included 33 items in six subgroups (nasal symptoms,
      sleep problems, headache, nonnasal symptoms, and practical and emotional
      problems) and general feeling. From 202 patients who completed the questionnaire
      before the procedures, 146 (72% of all patients) who were interviewed 6 months
      postoperatively were included in this study. Comparing preoperative data between
      followed up patients and missed patients showed no statistical difference among
      surgeries (p = 0.90). Comparison of patient's pre- and postoperative QOL showed a
      significant improvement in global QOL and in all questionnaire items (p < 0.0001
      in all comparisons). Comparison of QOL changes before and after surgery among
      different surgeries revealed no statistical difference (p = 0.282). Our data
      showed a significant improvement in each surgery but the amount of improvement in
      different surgeries was almost constant.

PMID- 22852124
TI  - Rhinologic issues in pregnancy.
AB  - The diagnosis and treatment of rhinitis, sinusitis, and epistaxis during
      pregnancy present unique challenges to the otolaryngologist. Poorly controlled
      sinonasal disease may have significant adverse effects on the mother's quality of
      life and pregnancy outcomes and the lack of adequately controlled safety data
      limits the clinician's ability to make informed decisions about management. At
      the conclusion of this discussion, the reader should be familiar with the
      available literature and evidence-based guidelines regarding the safety and
      indications for radiographic imaging, clinical testing, medical intervention, and
      surgical treatment of sinonasal disease in pregnant patients. A review was
      performed of pertinent guidelines regarding the management of gestational
      rhinitis, sinusitis, and epistaxis, including the diagnostic and therapeutic
      limitations and physiological changes specific to pregnancy. A study population
      of four patients was analyzed to highlight the steps of management by reviewing
      the patient charts including pertinent history, physical examination, clinical
      course, and operative reports. Two patients with epistaxis and two patients with
      rhinosinusitis ranging from 27 to 38 years of age and between 16 and 35 weeks
      gestation were analyzed. The treatment of sinonasal disease during pregnancy is
      challenging and a thorough knowledge of the available medical evidence and
      treatment guidelines is necessary to optimize pregnancy outcomes. When the
      severity of disease precludes the possibility of delaying treatment, the
      clinician should provide a limited intervention that optimizes the mother's
      health without placing the fetus at significant risk.

PMID- 22852125
TI  - Sensitization rate and clinical profile of Congolese patients with rhinitis.
AB  - In the African continent, the sensitization pattern and clinical profile are
      unknown in patients with rhinitis/rhinosinusitis attending the outpatient ear,
      nose, and throat (ENT) clinics. We therefore aimed to analyze the clinical
      characteristics of rhinitis/rhinosinusitis patients in Democratic Republic of
      Congo (DRC), classify allergic rhinitis (AR) according to the Allergic Rhinitis
      and Its Impact on Asthma criteria, and evaluate the sensitization profile and its
      associated factors. From January to May 2009, 423 patients with rhinitis symptoms
      attending the Outpatient ENT clinic of the University Hospital and Saint Joseph
      Hospital of Kinshasa were evaluated for allergy symptoms, severity, and duration
      of symptoms and underwent skin-prick tests (SPTs) for a panel of 15 allergens. Of
      423 patients 35.2% had positive SPT results, with 40.9% showing
      polysensitization. Dermatophagoides pteronyssinus (DPT) (68.5%) and cockroach
      (36.2%) were the most common allergens among sensitized patients. Patients with
      rhinitis/rhinosinusitis mainly presented in decreasing order with sneezing,
      facial pain/pressure, nasal obstruction, postnasal discharge, nose itching, clear
      nasal discharge, and eye itching. Persistent and moderate/severe AR represented
      61.4 and 69.3%, respectively. Sensitization was independently associated with
      younger age, rhinoconjunctivitis, and reaction to nonspecific trigger factors. In
      conclusion, 35.2% of patients attending the ENT Outpatient Clinic in DRC for
      rhinitis problems had a positive SPT to at least one allergen, with mainly DPT
      and cockroach allergens being involved; and a substantial portion showed
      persistent and moderate/severe AR. Therefore, allergy should not be neglected as
      an etiologic factor in rhinologic disease in the African continent.

PMID- 22852126
TI  - Mite-induced inflammation: More than allergy.
AB  - Clinical observations have suggested that there is an association of atopic
      conditions with hypersensitivity reactions to nonsteroidal anti-inflammatory
      drugs (NSAIDs). This relationship has been especially present in patients
      allergic to mites. This study was designed to review clinical and experimental
      evidence linking atopy, mite allergy, and hypersensitivity to aspirin and NSAIDs
      and discuss the possible mechanisms explaining this association. A review of the
      medical literature concerning the association of atopic diseases, mite
      hypersensitivity, and intolerance to NSAIDs using PubMed and other relevant
      articles is presented. NSAID-sensitive patients are frequently atopic and
      allergic to mites, and patients who develop oral mite anaphylaxis (OMA) show an
      increased prevalence of NSAID hypersensitivity. The study of atopic, mite
      sensitive patients, who experience urticaria and angioedema when exposed to
      NSAIDs and patients with OMA suggests an interesting interaction between atopic
      allergy and disorders of leukotriene synthesis or metabolism. Various mechanisms
      that could be involved in this interaction are presented, including genetic
      factors, inhibition of cyclooxygenase-1, and other effects (not related to IgE
      sensitization) of mite constituents on the immune system. The association of mite
      hypersensitivity with aspirin/NSAIDs intolerance has been confirmed and provides
      additional clues to various nonallergic pathways that may contribute to the acute
      and chronic inflammatory process observed in atopic, mite-allergic, individuals.
      The clinical relevance of these observations is presently under investigation.

PMID- 22852127
TI  - Regulation of dendritic cell functions against harmful respiratory pathogens by a
      cysteinyl leukotrienes receptor antagonist.
AB  - Cysteinyl leukotriene receptor antagonist (LTRA) is a widely used medicine for
      asthma. Cysteinyl leukotrienes (cysLTs) are involved in the regulation of
      dendritic cell (DC) function. However, the effects of LTRA on DC-related
      antimicrobial immunity against harmful respiratory pathogens remain unknown. The
      purpose of this study was to examine the effects of LTRA administered in vivo on
      DC function against representative respiratory pathogens in vitro. Pulmonary DCs
      were isolated from four groups of mice: control, mite allergen sensitized (AS),
      and AS mice treated with the corticosteroid dexamethasone (Dex) or with the LTRA
      pranlukast (Prl). These DCs were incubated with mite allergen, lipopolysaccharide
      (LPS), Aspergillus fumigatus, or respiratory syncytial virus (RSV). IL-10 and IL
      12 production was then determined. Dex treatment significantly inhibited
      lipopolysaccharide (LPS)-induced IL-10 and IL-12 production as well as baseline
      IL-12 production in AS mice. The Prl did not significantly inhibit LPS-induced IL
      10 and IL-12 production in AS mice. More importantly, Prl significantly increased
      IL-10 and IL-12 in AS mice after RSV infection. This study shows that LTRA that
      is used for asthma potentially up-regulates antimicrobial immunity through
      modulation of DC function against some respiratory infections without
      immunosuppression.

PMID- 22852128
TI  - Polymorphic variants of interleukin-13 R130Q, interleukin-4 T589C, interleukin
      4RA I50V, and interleukin-4RA Q576R in allergic rhinitis: A pilot study.
AB  - The development of allergic rhinitis is considered to be caused by the complex
      interactions between genetic predisposition and environmental factors.
      Polymorphisms in the interleukin (IL)-13/4/4RA pathway have previously been shown
      to be associated with atopic diseases. The purpose of this study was to determine
      the association between IL-13 R130Q, IL-4 T589C, IL4 receptor alpha (IL-4RA)
      I50V, or IL-4RA Q576R polymorphisms and risk of allergic rhinitis in a hospital
      based Malaysian population. A case-control pilot study was undertaken and
      genotyping of these polymorphisms was performed using polymerase chain reaction
      restriction fragment length polymorphism on 54 allergic rhinitis patients and 45
      healthy individuals. Polymorphism of IL-13 R130Q showed significant difference in
      genotype (p = 0.048) and allele (p = 0.002) frequencies in allergic rhinitis when
      compared with healthy controls. Individuals who were GA heterozygotes (adjusted
      odds ratio [OR(adj)] = 3.567; 95% CI, 1.211-10.509), and carriers of A allele
      genotype (OR(adj) = 3.686; 95% CI, 1.300-10.451) and A allele (OR(adj) = 3.071;
      95% CI, 1.514-6.232) had an elevated risk of developing allergic rhinitis. The
      genotype and allele frequencies of IL-4 T589C, IL-4RA I50V, and IL-4RA Q576R
      polymorphisms were not significantly different between the allergic rhinitis
      patients and normal healthy individuals and did not show an associated risk with
      allergic rhinitis. Our findings indicate that polymorphic variant of IL-13 R130Q
      appears to be associated with increased risk for development of allergic rhinitis
      in a hospital-based Malaysian population but not IL-4 T589C, IL-4RA I50V, and IL
      4RA Q576 polymorphisms. Additional studies using larger sample size are required
      to confirm our findings and its exact role in allergic rhinitis.

PMID- 22852129
TI  - Locally destructive skull base lesion: IgG4-related sclerosing disease.
AB  - A unique case of IgG4(+) sclerosing disease was diagnosed in the sphenoid sinus,
      a previously unreported location, and was treated in a novel manner. This study
      describes the clinical presentation and management of IgG4 sclerosing disease in
      the paranasal sinuses. A retrospective case review and review of the medical
      literature were performed. A 38-year-old woman with a 2-year history of constant
      frontal headaches presented to our clinic. Imaging showed bony destruction of the
      sphenoid sinus and sellar floor. The patient underwent a right-sided
      sphenoidotomy with debridement and biopsy. Pathological evaluation showed a dense
      plasmacytic infiltrate with >150 IgG4(+) cells/high-power field. She was
      subsequently started on a nasal corticosteroid with improved patency of the
      sphenoid antrostomy. We report an unusual case of a middle-aged woman who
      presented with IgG4-sclerosing disease (IGSD) isolated to the sphenoid sinus.
      Although our knowledge concerning treatment in extrapancreatic organs is lacking,
      there is evidence that glucocorticoid treatment improves nasal sinus
      opacification on CT findings (Sato Y, Ohshima K, Ichimura K, et al., Ocular
      adnexal IgG4-related disease has uniform clinicopathology, Pathol Int 58:465-470,
      2008). This case study and literature review adds to the growing literature
      describing IGSD in the head and neck and more specifically isolated to the
      sphenoid sinus with preliminary data concerning local control with topical
      steroids.

PMID- 22852130
TI  - Congenital nasolacrimal duct cyst/dacryocystocele: An argument for a genetic
      basis.
AB  - Embryogenesis of a congenital nasolacrimal duct (NLD) cyst is attributed to the
      failure of the Hasner membrane of the NLD system to cannulate. Prenatal diagnosis
      of congenital NLD cysts supports the argument for a developmental error, with a
      postnatal prevalence of 6%. The role of a genetic basis for this malformation has
      never been ascribed. We present a set of monozygotic twins with bilateral
      congenital NLD cysts as an argument for a genetic basis of this entity. A case
      report and literature review were performed. We present two cases of bilateral
      congenital NLD cysts occurring in a set of monozygotic twins. Patients were
      delivered at 37 weeks via cesarean section. The pregnancy was complicated by
      preterm labor at 33 weeks requiring administration of terbutaline and
      betamethasone. At presentation, twin A had bilateral eye discharge, erythema, and
      swelling medial to the medial canthi as well as nasal obstruction. Computed
      tomography (CT) showed classic bilateral cystic masses in the inferior meatus.
      The diagnosis of bilateral infected congenital dacryocystoceles was made. Twin B
      initially presented with only bilateral eye discharge and CT showed a dilated NLD
      system. Twin B subsequently developed early signs of bilateral dacryocystoceles
      the following day. Both patients underwent lacrimal probing and endoscopic
      marsupialization of the dacryocystoceles. Biopsies were consistent with
      dacryocystocele. Dacryocystocele is a common presentation of unresolved neonatal
      NLD obstruction. This case report in a set of identical twins is an argument for
      a genetic basis for the formation of this lesion.

PMID- 22852131
TI  - Efficacy of medical therapy in treatment of chronic rhinosinusitis.
AB  - Uncomplicated chronic rhinosinusitis (CRS) is generally treated with medical
      therapy initially and surgery is contemplated only after medical therapy has
      failed. However, there is considerable variation in the medical treatment
      regimens used and studies defining their efficacy are few. The aim of this study
      was to determine the proportion of patients treated medically who responded
      sufficiently well so that surgery was not required. Subgroup analysis to identify
      clinical features that predicted a favorable response to medical therapy was also
      performed. Eighty patients referred to the Otorhinolaryngology Clinic at North
      Shore Hospital were treated with a standardized medical therapy protocol (oral
      prednisone for 3 weeks, oral antibiotics and ongoing saline lavage and intranasal
      budesonide spray). Symptom scores were collected before and after medical
      therapy. Clinical features such as presence of polyps, asthma, and aspirin
      hypersensitivity were recorded. Failure of medical therapy was defined as the
      persistence of significant CRS symptoms, and those patients who failed medical
      therapy were offered surgery. Follow-up data were available for 72 (90%)
      patients. Of this group, 52.5%, (95% CI, 42.7%, 62.2%) failed to respond
      adequately to medical therapy and were offered surgery. The remaining patients
      (37.5%) were successfully treated with medical therapy and did not require
      surgery at the time of follow-up. The premedical therapy symptom scores were
      significantly higher than the postmedical therapy symptom scores (p < 0.01). The
      symptom scores of those patients postmedical therapy who proceeded to have
      surgery were significantly higher than the group who responded well to maximum
      medical therapy (MMT) and did not require surgery (p < 0.0001). There were no
      significant differences in the proportion of patients with asthma, aspirin
      sensitivity, or polyps between the groups failing or not failing MMT. In
      approximately one-third of patients with CRS, medical therapy improved symptoms
      sufficiently so that surgical therapy was avoided. Patients with more severe
      symptoms tended not to respond as well as those with less severe symptoms. Long
      term follow-up is required for the group of responders to determine how many will
      eventually relapse.

PMID- 22852132
TI  - Comparative proteomic analysis of drug sodium iron chlorophyllin addition to Hep
      3B cell line.
AB  - The human hepatoma 3B cell line was chosen as an experimental model for in vitro
      test of drug screening. The drugs included chlorophyllin and its derivatives such
      as fluo-chlorophyllin, sodium copper chlorophyllin, and sodium iron
      chlorophyllin. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT) method was used in this study to obtain the primary screening results. The
      results showed that sodium iron chlorophyllin had the best LC(50) value.
      Proteomic analysis was then performed for further investigation of the effect of
      sodium iron chlorophyllin addition to the Hep 3B cell line. The proteins
      identified from a total protein extract of Hep 3B before and after the drug
      addition were compared by two-dimensional-gel-electrophoresis. Then 32 three-fold
      differentially expressed proteins were successfully identified by MALDI-TOF-TOF
      MS. There are 29 unique proteins among those identified proteins. These proteins
      include proliferating cell nuclear antigen (PCNA), T-complex protein,
      heterogeneous nuclear protein, nucleophosmin, heat shock protein A5 (HspA5) and
      peroxiredoxin. HspA5 is one of the proteins which are involved in protecting
      cancer cells against stress-induced apoptosis in cultured cells, protecting them
      against apoptosis through various mechanisms. Peroxiredoxin has anti-oxidant
      function and is related to cell proliferation, and signal transduction. It can
      protect the oxidation of other proteins. Peroxiredoxin has a close relationship
      with cancer and can eventually become a disease biomarker. This might help to
      develop a novel treatment method for carcinoma cancer.

PMID- 22852133
TI  - A novel high selectivity chemiluminescence sensor for fenvalerate based on double
      sided hollow molecularly imprinted materials.
AB  - Novel fenvalerate double-sided hollow molecularly imprinted microspheres
      (fenvalerate-DHMIMs) were fabricated by in situ polymerization with the help of
      mesoporous silica microspheres (MSMs) in this paper for the very first time.
      Scanning electron microscope was employed to characterize the surface morphology
      of the fenvalerate-DHMIMs. Taking advantage of the quenching effect of
      fenvalerate on the luminol-H(2)O(2)-NaOH chemiluminescence system, a new model
      was established to determine fenvalerate by a highly selective flow injection
      chemiluminescence method. The traditional flow-through cell was replaced by a
      novel Y-shaped column. The chemiluminescence intensity was linear with
      fenvalerate concentration over the range of 5.0 * 10(-8) to 2.0 * 10(-5) g mL(-1)
      and the detection limit was 2.2 * 10(-8) g mL(-1). The relative standard
      deviation (RSD) for the determination of 2.0 * 10(-6) g mL(-1) fenvalerate was
      1.4% (n = 11). The proposed method was applied to the determination of
      fenvalerate in real samples with satisfactory results.

PMID- 22852134
TI  - Exploratory urinary metabolic biomarkers and pathways using UPLC-Q-TOF-HDMS
      coupled with pattern recognition approach.
AB  - Metabolomics represents an emerging and powerful discipline concerned with the
      comprehensive analysis of small molecules and provides a powerful approach to
      discover biomarkers in biological systems. Recent development of biomarkers for
      diagnosis and therapeutic monitoring of liver-stagnation and spleen-deficiency
      syndrome (LSS)-type disease remains challenging. This study was undertaken to
      discover novel potential biomarkers for the non-invasive early diagnosis of human
      LSS. Urine samples which are potentially a rich source of metabolites were
      collected from patients with LSS, together with healthy control samples.
      Metabolite profiling was performed by ultra-performance liquid
      chromatography/electrospray-ionization synapt high-definition mass spectrometry
      (UPLC-Q-TOF-HDMS) in conjunction with multivariate data analysis and ingenuity
      pathway analysis that were used to select the metabolites to be used for the non
      invasive diagnosis of LSS. Twelve urinary differential metabolites contributing
      to the complete separation of LSS patients from matched healthy controls were
      identified involving several key metabolic pathways such as pentose and
      glucuronate interconversions, ascorbate, aldarate, cysteine, methionine,
      tyrosine, tryptophan, amino sugar and nucleotide sugar metabolism. More
      importantly, of the 12 differential metabolites, 4 metabolite markers,
      prolylhydroxyproline, L-homocystine, 2-octenoylcarnitine and alpha-N-phenylacetyl
      L-glutamine, were effective for the diagnosis of human LSS, with an achieved
      sensitivity of 93.0%. These results demonstrate that robust metabolomics has the
      potential as a non-invasive strategy and promising screening tool to evaluate the
      potential of these metabolites in the early diagnosis of LSS patients and
      provides new insight into pathophysiological mechanisms.

PMID- 22852135
TI  - A general approach to the synthesis of enantiopure 19-nor-vitamin D3 and its C-2
      phosphate analogs prepared from cyclohexadienyl sulfone.
AB  - A synthesis of enantiopure 19-nor-Vitamin D(3) and its C-2 substituted cyclic
      phosphate analogs is achieved via in situ trapping of an alpha-sulfonyl anion
      with a CD-ring allyl chloride and 1,2-eliminative desulfonylation exploiting the
      basic properties of TBAF. The A-ring is prepared via anti-selective dithiane
      addition to vinyl sulfone and LiBH(4) mediated sequential bis reduction of an
      epoxy vinyl sulfone.

PMID- 22852136
TI  - Professor Harold Fox.

PMID- 22852137
TI  - Abstracts of the XXX International Congress of Psychology. July 22-27, 2012. Cape
      Town, South Africa.

PMID- 22852138
TI  - FDA paves the way for pre-exposure HIV prophylaxis.

PMID- 22852139
TI  - Greek science: hope in crisis.

PMID- 22852140
TI  - Profile: MLW optimises community engagement in research.

PMID- 22852141
TI  - How bad ideas gain social traction.

PMID- 22852143
TI  - [International differences in the guidelines for ADHD diagnosis and treatment].

PMID- 22852142
TI  - A potential in vitro and in vivo anti-HIV drug screening system for Chinese
      herbal medicines.
AB  - Chinese herbal medicines are often applied as an alternative therapy for viral
      diseases. However, the development of anti-HIV herbal drugs has proceeded slowly,
      partly because of the lack of a high-throughput system for screening these drugs.
      The present study evaluated 16 herbal medicines for anti-HIV activities in vitro
      and in vivo. Herbal medicines were first screened for the ability to regulate C-X
      C receptor 4 (CXCR4) and C-C receptor 5 (CCR5) promoter activities. A single
      round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to
      identify potential anti-HIV mechanisms. CD4+ T cells from healthy volunteers were
      examined for changes in CXCR4 and CCR5 levels. HIV-1 replication was evaluated by
      ELISA. Spica Prunellae and Herba Andrographitis were found to down-regulate the
      activities of both the CXCR4 and CCR5 promoters. Also, Spica Prunellae and Herba
      Andrographitis (>1000 MUM) inhibited HIV-1 in a dose-dependent manner. CXCR4 and
      CCR5 levels were reduced in CD4+ T cells from healthy volunteers (p<0.05). Spica
      Prunellae and Herba Andrographitis (EC50: 3.18 and 5.49 MUg/mL, respectively)
      could suppress cell fusion and decrease p24 antigen. In conclusion, the data
      demonstrated that Spica Prunellae and Herba Andrographitis possessed anti-HIV-1
      capabilities, perhaps through the inhibition of the CXCR4 and CCR5 promoters and
      HIV-1 replication.

PMID- 22852145
TI  - States draw battle lines. Hospitals wary as GOP governors vow to fight Medicaid
      expansion.
AB  - In the wake of the U.S. Supreme Court upholding the bulk of the health reform
      law, the focus shifts to the states. Many GOP governors are vowing to refuse the
      Medicaid expansion that's part of the ACA. "There's a limited pool of funds
      available for Medicaid expansion; would those funds be redirected from Jackson to
      fund the Medicaid expansion program or not?" said Brian Dean, left, vice
      president of finance at Jackson Health System, Miami.

PMID- 22852146
TI  - What's ahead.

PMID- 22852147
TI  - A safer, faster way for postoperative x-rays.

PMID- 22852148
TI  - New consensus statement for cardiac cath labs.

PMID- 22852149
TI  - 'A big issue'. Providers grapple with Medicaid provision.

PMID- 22852150
TI  - The long, long road to national health reform (a short history).

PMID- 22852152
TI  - Medicare turnabout. Signs point against entitlement reform this year.

PMID- 22852151
TI  - Was chloroform inhalation anesthesia tried before 1847?

PMID- 22852153
TI  - Getting connected.

PMID- 22852154
TI  - Largest healthcare fraud settlements. Ranked by amount recovered under the False
      Claims Act in 2011.

PMID- 22852155
TI  - Provider tax feud. States using proceeds to boost federal funding.

PMID- 22852157
TI  - Top business graduate schools for physician-executives.

PMID- 22852156
TI  - Insurers fail to impress. Vows to keep parts of ACA not enough, critics say.

PMID- 22852158
TI  - Chronic lung disease.  Pay attention to your breath.

PMID- 22852159
TI  - Increased emphasis on exercise for osteoarthritis.

PMID- 22852160
TI  - New drug shows promise for advanced colorectal cancer.

PMID- 22852161
TI  - Hand tremors.  Not always Parkinson's disease.

PMID- 22852162
TI  - Tinnitus.  Notice the noise less.

PMID- 22852163
TI  - Health tips.  Freshen bad breath.

PMID- 22852164
TI  - Preoperative evaluation. Avoiding surprises.

PMID- 22852165
TI  - What's the difference between a regular bunion and a tailor's bunion?

PMID- 22852166
TI  - I got swimmer's itch last summer.  How do I avoid getting it again?

PMID- 22852167
TI  - The Journal of Mental Health Policy and Economics. Editorial.

PMID- 22852168
TI  - beta-blockers in COPD - yes, it's OK (with care).

PMID- 22852169
TI  - Risk factor. How biology can explain what drives banks to the brink of disaster.

PMID- 22852170
TI  - Eat this? How edible packaging could shake up the food industry.

PMID- 22852171
TI  - Nightmare scenario.

PMID- 22852172
TI  - Woman enough? Inside the controversial world of olympic gender testing.

PMID- 22852173
TI  - Replacing the mouse.

PMID- 22852174
TI  - It is not what you leave behind ... it is what you take with you that counts!

PMID- 22852175
TI  - "What's the clicking sound"?

PMID- 22852176
TI  - Insurance conncection: the Patient Protection and Affordable Care Act of 2010.

PMID- 22852177
TI  - The value of media promotion.

PMID- 22852178
TI  - Care is being compromised by treatment in corridors.

PMID- 22852179
TI  - Setting new standards for the emergency care of children.

PMID- 22852180
TI  - Managing major incidents.

PMID- 22852181
TI  - Leadership matters.

PMID- 22852182
TI  - Improving parental first-aid practices.
AB  - Every day, children present to emergency departments (EDs) with injuries
      sustained at home, school and elsewhere. In the authors' experience, little, if
      any, first-aid measures or administration of pain relief are initiated before
      arrival at the ED. Articles on accident prevention are easily sourced, but
      studies of the general population's knowledge of first-aid skills are scarce.
      This article examines the research on parents' or guardians' pre-hospital
      knowledge of first aid, analgesia and non-pharmacological methods of pain relief
      for children who have been injured. It also discusses the literature on accident
      prevention.

PMID- 22852183
TI  - Volunteer nurses on track for the summer events.
AB  - Many emergency nurses will have volunteered to join 5,000 medical staff at this
      year's Olympic and Paralympic Games, in London. This article tells the stories of
      three such nurses from an emergency department in Newport.

PMID- 22852184
TI  - How Greek healthcare services are affected by the Euro crisis.
AB  - Greece's economic crisis is having a detrimental effect on the country's health
      service. Government cutbacks have forced hospitals to merge, reduced nurse-to
      patient ratios and have led to pay cuts and poorer conditions for staff.
      Emergency nurses must work longer hours with fewer resources for less money, when
      emergency admissions in the public sector are rising as a result of the economic
      pressures on Greek society.

PMID- 22852185
TI  - Treating envenomation caused by fish sting.
AB  - The lesser weever fish is found around the coastline of the UK, particularly in
      the south and west of England. The spines on the fish's first dorsal fin and gill
      covers release a poison that can cause excruciating pain in anyone who stands on
      them. Emergency staff should be aware, therefore, of the symptoms of lesser
      weever fish stings in patients who present with severe pain in the foot.
      Immersion of the foot in hot water is the most effective treatment.

PMID- 22852186
TI  - Caring for patients in the right place at the right time.
AB  - The Department of Health (2001) has recommended that emergency departments (EDs)
      in England introduce patient-streaming systems to manage patient flow and reduce
      time to initial triage. This article describes how one London ED has introduced
      such a system with reference to Waterman et al's (1980) Seven S model and the NHS
      Institute for Innovation and Improvement's (2008) Plan Do Study Act cycle. It
      also discusses the importance of staff and stakeholder involvement in such
      projects and makes recommendations for the role of streaming nurses in EDs.

PMID- 22852187
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards.
AB  - The 2011 John M. Eisenberg Patient Safety and Quality Awards were presented on
      April 5, 2012, in Washington, D.C. Individual award recipients were interviewed
      for this issue, and organization or group award recipients contributed articles
      describing their work.

PMID- 22852188
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards. Individual Achievement.
      Interview by Eric J. Thomas.
AB  - Dr. Shine, who, as president, led the Institute of Medicine's focus on quality
      and patient safety, describes initiatives at the University of Texas System,
      including quality improvement training, systems engineering, assessment of
      projects' economic impact, and dissemination of good practices.

PMID- 22852189
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards. Honorary Award for
      Lifetime Achievement. Interview by Steven Berman.
AB  - Having a chronic disease has enriched Dr Loeb's understanding of the meaning of
      patient-centered care: "It's fine being a health care consumer when you're well.
      However, when you become ill, you become a patient, which is much different".

PMID- 22852190
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards. Mentored
      implementation: building leaders and achieving results through a collaborative
      improvement model. Innovation in patient safety and quality at the national
      level.
AB  - BACKGROUND: The Society of Hospital Medicine (SHM) created "Mentored
      Implementation" (MI) programs with the dual aims of educating and mentoring
      hospitalists and their quality improvement (QI) teams and accelerating
      improvement in the inpatient setting in three signature programs: Venous
      Thromboembolism (VTE) Prevention, Glycemic Control, and Project BOOST (Better
      Outcomes for Older adults through Safe Transitions). METHODS: More than 300
      hospital improvement teams were enrolled in SHM MI programs in a series of
      cohorts. Hospitalist mentors worked with individual hospitals/health systems to
      guide local teams through the life cycle of a QI project. Implementation Guides
      and comprehensive Web-based "Resource Rooms," as well as the mentor's own
      experience, provided best-practice definitions, practical implementation tips,
      measurement strategies, and other tools. E-mail interactions and mentoring were
      augmented by regularly scheduled teleconferences; group webinars; and, in some
      instances, a site visit. Performance was tracked in a centralized data tracking
      center. RESULTS: Preliminary data on all three MI programs show significant
      improvement in patient outcomes, as well as enhancements of communication and
      leadership skills of the hospitalists and their QI teams. CONCLUSIONS: Although
      objective data on outcomes and process measures for the MI program's efficacy
      remain preliminary at this time, the maturing data tracking system, multiple
      awards, and early results indicate that the MI programs are successful in
      providing QI training and accelerating improvement efforts.

PMID- 22852191
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards. The effect of a novel
      Housestaff Quality Council on quality and patient safety. Innovation in patient
      safety and quality at the local level.
AB  - BACKGROUND: In 2008 New York-Presbyterian Hospital (NYP)/Weill Cornell Medical
      Center, New York City, the largest not-for-profit, nonsectarian hospital in the
      United States, created and implemented a novel approach--the Housestaff Quality
      Council (HQC)--to engaging house-staff in quality and patient safety activities.
      METHODS: The HQC represented an innovative collaboration between the housestaff,
      the Department of Anesthesiology, the Division of Quality and Patient Safety, the
      Office of Graduate Medical Education, and senior leadership. As key managers of
      patient care, the housestaff sought to become involved in the quality and patient
      safety decision- and policy-making processes at the hospital. Its members were
      determined to decrease or minimize adverse events by facilitating multimodal
      communication, ensuring smart work flow, and measuring outcomes to determine best
      practices. The HQC, which also included frontline hospital staff or managers from
      areas such as nursing, pharmacy, and information technology, aligned its
      initiatives with those of the division of quality and patient safety and embarked
      on two projects--medication reconciliation and use of the electronic medical
      record. More than three years later, the resulting improvements have been
      sustained and three new projects--hand hygiene, central line-associated
      bloodstream infections, and patient handoffs--have been initiated. CONCLUSIONS:
      The HQC model is highly replicable at other teaching institutions as a
      complementary approach to their other quality and patient safety initiatives.
      However, the ability to sustain positive momentum is dependent on the ability of
      residents to invest time and effort in the face of a demanding residency training
      schedule and focus on specialty-specific clinical and research activities.

PMID- 22852192
TI  - 2011 John M. Eisenberg Patient Safety and Quality Awards. The Henry Ford Health
      System No Harm Campaign: a comprehensive model to reduce harm and save lives.
      innovation in patient safety and quality at the local level.
AB  - BACKGROUND: In 2008 Henry Ford Health System launched its "No Harm Campaign,"
      designed to integrate harm-reduction interventions into a systemwide initiative
      and, ultimately, to eliminate harm from the health care experience. METHODS: The
      No Harm Campaign aims to decrease harm events through enhancing the system's
      culture of safety by reporting and studying harm events, researching causality,
      identifying priorities, and redesigning care to eliminate harm. The campaign uses
      a comprehensive set of 27 measures for harm reduction, covering infection-,
      medication-, and procedure-related harm, as well as other types of harm, all of
      which are combined to comprise a unique global harm score. The campaign's
      objective is to reduce all-cause harm events systemwide by 50% by 2013. A wide
      range of communication processes, from systemwide leadership retreats to daily e
      mail news sent to all employees and physicians, is used to promote the campaign.
      In addition, the campaign is on the intranet "Knowledge Wall," where monthly
      dashboards, meeting minutes, and best practices and the work of our teams and
      collaboratives are documented and shared. RESULTS: From 2008 through 2011, a 31%
      reduction in harm events and an 18% reduction in inpatient mortality occurred
      systemwide. DISCUSSION: Building infrastructure, creating a culture of safety,
      providing employee training and education, and improving work process design are
      critical to systemwide implementation of harm-reduction efforts. Key actions for
      ongoing success focus on leadership, disseminating performance, putting everyone
      to work, and stealing ideas through national and local collaborations. A
      financial model was created to assess cost-savings of reducing harm events; early
      results total nearly $10 million in four years.

PMID- 22852193
TI  - Using a risk assessment approach to determine which factors influence whether
      partially bilingual physicians rely on their non-English language skills or call
      an interpreter.
AB  - BACKGROUND: Partially bilingual physicians may weigh a number of factors in
      deciding whether to use their own limited non-English language skills or call an
      interpreter when caring for patients with limited English proficiency. Yet little
      is known about this decision process or how it might fail. In a patient safety
      approach to exploration of this complex, potentially high-stakes decision, key
      risk factors that may contribute to miscommunication during health care
      encounters in non-English languages were identified. METHODS: The Healthcare
      Failure Mode and Effects Analysis (HFMEA) method was adapted to examine the
      decision process. An initial set of possible decision factors was presented to a
      national expert panel of eight physicians, who modified and expanded the list of
      factors and then rated each according to four scales: Frequency, Importance,
      Amenability to Intervention, and Detectability. A "5 Whys" approach was used to
      examine underlying causes of these failure modes and generate potential
      interventions. FINDINGS: Nine factors were described that could lead physicians
      to use their own skills rather than an interpreter when that decision might pose
      unacceptable risk. The highest-priority factor was lack of knowledge regarding
      the value of using a trained interpreter and how to work with a trained
      interpreter effectively. For the top failure mode, a sample hypothetical 5 Whys
      exercise shows how to examine potential underlying causes and produce
      recommendations. CONCLUSIONS: A variety of discrete factors can have important
      effects on physicians' decisions to use their own non-English language skills or
      an interpreter. Because this decision can affect patient safety, organizations
      and policy makers should use these factors to guide local efforts to examine
      these issues and develop quality improvement and safety activities.

PMID- 22852194
TI  - Inclusion of all: championing diversity includes respecting sexual orientation
      and gender identification.

PMID- 22852196
TI  - Maximizing human performance: know your high performers and re-recruit them every
      day.

PMID- 22852195
TI  - Boosting clinical productivity.

PMID- 22852197
TI  - All of us: embracing diversity in healthcare.

PMID- 22852198
TI  - Leadership: being a servant leader.

PMID- 22852199
TI  - Communication: the art of saying no.

PMID- 22852200
TI  - Management: evidence-based human capital management.

PMID- 22852201
TI  - Comparing ethics and compliance programs. Each is unique, but overlaps are key to
      clarifying organizational roles.

PMID- 22852202
TI  - The business case for patient flow. Unique approaches to patient flow improve the
      patient experience and the bottom line.

PMID- 22852203
TI  - Providing continuing care for cancer patients. Use of rehabilitation program
      improves outcomes, satisfaction.

PMID- 22852204
TI  - Federal elections, the economy and healthcare. Much for executives to consider
      between now and November.

PMID- 22852205
TI  - Mentoring and preparing the next generation. Critical skills are best learned
      when passed from leader to leader.

PMID- 22852206
TI  - Empowering patient-centered care across the continuum. Enhancing relationships
      and improving communication between providers.

PMID- 22852207
TI  - Creating a culture of excellence. It's not as difficult as you might think.

PMID- 22852208
TI  - Technology spending and accountable care. CEO's job is to help find a viable
      path.

PMID- 22852209
TI  - Statement on diversity.

PMID- 22852210
TI  - Contra-lateral needling in the treatment of hemiplegia due to acute ischemic
      stroke.
AB  - Contra-lateral Needling, a traditional acupuncture technique, means contra
      lateral acupuncture by inserting needles into acupoints on the relative healthy
      side of the body opposite to the injured side to treat diseases such as apoplexy
      with high efficacy. However, there are not many well-designed and controlled
      clinical evidences found in the literature. Therefore the present study was
      designed to assess its therapeutic responses in the treatment of hemiplegia due
      to acute ischemic stroke. A clinical study was conducted with randomly selected
      106 patients who have acute ischemic stroke confirmed by MRI. The subjects were
      assigned into 3 groups: 45 in the contra-lateral needling group received
      acupuncture on the unaffected limbs; 45 in the conventional acupuncture group
      received acupuncture on the hemiplegic limbs; and 16 in the non-acupuncture group
      received the similar medical and nursing care as subjects in other two groups but
      no acupuncture treatment. Acupuncture was given daily for 45 minutes for 30 days.
      The clinical therapeutic responses rate, Neurological Deficits Score (NDS),
      Modified Barthel Index (MBI) and Fugl-Meger Assertion (FMA) were used to evaluate
      the effectiveness of 30 days treatment. The therapeutic response rate of the
      contra-lateral needling group was 46.67%, while 31.11% in the conventional
      acupuncture group, and 18.75% in the non-acupuncture group. The NDS of Contra
      lateral needling group decreased more significantly than that of the conventional
      acupuncture group (p < 0.01). The study also found that the MBI and FMA of Contra
      lateral needling group increased more significantly than those of the
      conventional acupuncture group (p < 0.01, respectively). Contra-lateral needling
      might be more effective than the conventional acupuncture in the treatment of
      hemiplegia due to acute ischemic stroke in terms of increasing the recovery of
      neurological functions, promoting ADL (activities for daily living)
      rehabilitation and the limbs motor function.

PMID- 22852211
TI  - Newly discovered quick, non-invasive screening method of bone marrow malignancies
      including various leukemias, Hodgkin's lymphoma, non-Hodgkin's lymphoma, &
      multiple myeloma by abnormality of small rectangular area within bone marrow
      organ representation areas of the face.
AB  - Diagnoses of bone marrow associated malignancies such as Acute & Chronic
      Lymphocytic Leukemia, Acute & Chronic Myelogenous (Myeloid) Leukemia, Hodgkin's
      Lymphoma & Non-Hodgkin's Lymphoma, and Multiple Myeloma are often missed without
      a blood test. However, in 2008, Omura Y reported several newly discovered organ
      representation areas that exist between the lower end of the eyebrows and upper
      end of the upper eyelid. This space was divided into 5 organ representation
      areas. The first space (more than 1/4 of entire space) near the side of the face
      (temple) is the bone marrow representation area (BMRA). Therefore, we examined
      the bone marrow representation areas non-invasively using the Bi-Digital O-Ring
      Test (BDORT). When the small rectangular shaped part of the BMRA is strong
      negative (-) with more than -2, often there is a malignancy associated with bone
      marrow. In this area, we found 1) Integrin alpha5beta1 & Oncogen C-fos Ab2
      increased very significantly between 125-300 ng BDORT units; 2) very high
      Chrysotile Asbestos (0.11-0.14 mg); 3) markedly reduced Acetylcholine of less
      than 1 ng; 4) significantly reduced telomere of less than 1 yg (= 10(-24) g); and
      5) Increased 8-OH-dG (often more than 5 ng). Once the abnormal small rectangular
      area is localized by BDORT, by detecting the specific microscope slide which
      produces EMF (electromagnetic field) resonance, one can diagnose these
      malignancies non-invasively in about 10 minutes. When a subject has any one of
      the above 7 types of bone marrow associated malignancies, the 5 aforementioned
      abnormal parameters can be detected. When Acetylcholine is markedly reduced to
      0.25 ng or less, 8-OH-dG is 10 ng or higher, and Sirtuin 1 (one of the 7
      mammalian longevity genes products) in both the Hippocampus and the body is 0.025
      pg or less, most of the patients have a very poor prognosis. However, we found
      that increasing normal cell telomere & longevity gene product Sirtuin 1 can often
      improve both pathology & prognosis. All measurements are in BDORT units (the
      weight required to produce maximum EMF resonance).

PMID- 22852212
TI  - Sedating the apprehensive debilitated patients for dental procedures by combining
      parenteral sedation and hypnosis with supplemental acupuncture therapy.
AB  - Treating apprehensive debilitated patients (i.e. geriatric patients, patients
      with cardiac, pulmonary, kidney, or liver diseases, and those with other severe
      systemic conditions) for dental procedures can cause unexpected medical
      complications such as cardiac arrest, stroke, asthma or shock, etc. Due to
      diminishing functional capacities of their organs, sedating those patients with
      sedative drugs in normal regular dosage could increase the risk of adverse events
      for this group of patients and can also increase the risk of liability for the
      clinician. The authors treated 34 apprehensive dental patients with a combination
      technique using parenteral sedation and hypnosis together with acupuncture. We
      used Bi-Digital O-Ring Test (BDORT) to select the compatible sedative drugs and
      to individualize the dosage suitable to the patient's medical condition.
      Oftentimes, BDORT predetermined dosage amounts to a fraction of regular dosage
      that is normally recommended by manufacturer for regular healthy patients. Such a
      reduced dosage, though benign to patient, may be insufficient to render a patient
      to the sedation level for dental treatment. Nevertheless, hypnosis with
      acupuncture can be applied to potentiate the therapeutic effect of parenteral
      sedation, thereby reducing the amount of sedative agents required to alleviate
      patient anxiety. The results indicated that hypnosis with acupuncture and BDORT
      could effectively allow the reduction of the sedative dosage and may beneficially
      provide a safe and comfortable situation for the debilitated patients to receive
      the necessary treatment.

PMID- 22852213
TI  - A new look at genital herpes: the critical role of the laboratory in diagnosis
      and management.

PMID- 22852214
TI  - Acute promyelocytic leukemia with t(15;17): a case study.
AB  - Acute promyelocytic leukemia (APL with t15;17) is a disease characterized by
      abnormal proliferation of promyelocytic cells in the peripheral blood and bone
      marrow, along with coagulopathy and thrombocytopenia. It is a variation of AML
      that frequently exhibits a typical chromosomal translocation. Laboratory analysis
      and confirmatory testing for the fusion gene make diagnosis and treatment of APL
      with t(15;17) possible.

PMID- 22852215
TI  - Interesting times for clinical chemistry.

PMID- 22852216
TI  - Right-sizing your lab's diagnostic capabilities using next-generation POC
      analyzers.

PMID- 22852217
TI  - Benchtop flow cytometry helps monitor HIV in sub-Saharan Africa.

PMID- 22852218
TI  - Serum biomarkers for lung disease.

PMID- 22852219
TI  - Automated IHC/ISH slide staining systems: current technologies and other
      considerations.

PMID- 22852220
TI  - The gram stain goes molecular--quickly!

PMID- 22852221
TI  - Personalized medicine.

PMID- 22852223
TI  - Automated temperature monitoring.

PMID- 22852222
TI  - Patents and patients: the implications of the Prometheus v. Mayo Supreme Court
      decision.

PMID- 22852224
TI  - Legislative and regulatory mandates impact lab reimbursement.

PMID- 22852225
TI  - The importance of holistic nursing in end-of-life care.

PMID- 22852226
TI  - Strategic plan update: structure & governance task force.

PMID- 22852227
TI  - Death with dignity: a holistic approach.

PMID- 22852228
TI  - Cultural competency in grief and loss.

PMID- 22852229
TI  - Holistic nursing: Becoming a catalyst for conscious change at end of life.

PMID- 22852230
TI  - The activist nurse.

PMID- 22852231
TI  - People skills: will they make you or break you?

PMID- 22852232
TI  - NPs & PAs are headed to hospital settings.

PMID- 22852233
TI  - Managing acute stroke and preventing secondary stroke.

PMID- 22852234
TI  - Malpractice prevention: what NPs & PAs need to know.

PMID- 22852235
TI  - Peak performance: heading off drug interactions with sports supplements.

PMID- 22852236
TI  - Allergen immunotherapy: sticking it to seasonal allergies.

PMID- 22852237
TI  - Retail therapy health insurance is coming to a big-box discount store near you.

PMID- 22852238
TI  - Cells for sale. You're now allowed to pay for bone marrow. Could other tissues be
      next?

PMID- 22852239
TI  - And now, how to improve Obamacare.

PMID- 22852240
TI  - Here's what we know for sure: Obama's health care reform is constitutional.
      Congress may not hold states hostage to its every whim. And Chief Justice John
      Roberts is now in charge.

PMID- 22852241
TI  - Deliverance or disaster? Four former solicitors general weigh in on Roberts'
      ruling.

PMID- 22852242
TI  - Certifiably good. Chefs seek a new culinary seal of approval for healthy dishes.

PMID- 22852243
TI  - "Build on the forum's work to boost nursing".

PMID- 22852244
TI  - Warning: cuts pose HCAI risk.

PMID- 22852245
TI  - "We've upped our monitoring of maternity care services".

PMID- 22852246
TI  - As nurses, we can be so much more significant when we work together". Interview
      by Jenni Middleton.

PMID- 22852247
TI  - "Research is on the right topics if combined with clinical role".

PMID- 22852248
TI  - Using safety crosses for patient self-reflection.
AB  - The Productive Mental Health Ward programme has been developed to improve
      efficiency and safety in the NHS. Patients in a medium-secure mental health unit
      used patient safety crosses as a tool for self-reflection as part of their
      recovery journey. This article describes how the project was set up as well as
      initial findings.

PMID- 22852249
TI  - Preventing falls in patients with alcohol problems.
AB  - A ward implemented the Productive Ward programme to reduce falls. The importance
      of staff engagement is highlighted.

PMID- 22852250
TI  - How effective are nurses' medicine discussions?
AB  - BACKGROUND: Nurse prescribers face a daily challenge to optimise medicine-taking
      through effective communication with patients. AIM: To identify the content of,
      and participation in, medicine discussion between nurse prescribers and people
      with diabetes. METHOD: A purposive sample of 20 nurse prescribers regularly
      involved with patients with diabetes audio-recorded 59 of their routine
      consultations. RESULTS: Some 260 instances of medicine discussion were analysed.
      The frequency and type of discussion themes indicated the content of nurses'
      discussion was largely "instruction-based". DISCUSSION: Neither the content nor
      nature of nurses' medicine discussion was fully congruent with recent National
      Institute for Health and Clinical Excellence guidance. CONCLUSION: Despite
      favourable comparison with doctor-patient medication discussion, diabetes nurse
      prescribers' discussion appears limited in its content and interaction style.

PMID- 22852251
TI  - Developing clinical research nurses.
AB  - Clinical research nurses have a unique role in developing and contributing to
      high-quality care. This article discusses key policy recommendations on their
      support and development, and outlines a local project exploring the issues that
      research nurses face. It also makes recommendations to improve these nurses'
      training and profile.

PMID- 22852252
TI  - 60 seconds with Ruth Westerby.

PMID- 22852253
TI  - Support in tough situations.

PMID- 22852254
TI  - A one-to-one doesn't mean going head to head.

PMID- 22852255
TI  - [The example Rinkeby-Kista: Early intervention vital for the health of children
      interacting with social services].

PMID- 22852256
TI  - [A Cochrane report on open comparisons. The core of medicine is pushed away].

PMID- 22852257
TI  - [Dismantling of "Big Pharma" gives new impetus to the pharmaceutical sector.
      Dynamic life science clusters can increase Swedish competitiveness].

PMID- 22852258
TI  - [Risk of vitamin D deficiency among certain groups in Sweden. New recommendations
      can be considered--optimal vitamin D status still unknown].

PMID- 22852259
TI  - [Difficult to implement tobacco use cessation in the regular care routine].

PMID- 22852260
TI  - [Research on quality registries provides clinical benefit. Results from the
      National Prostate Cancer Registry].

PMID- 22852261
TI  - [Patients with cancer denied treatment with new expensive drugs].

PMID- 22852262
TI  - [Proposal on drug reviews lack structure and evidence].

PMID- 22852263
TI  - [Who supervises the supervisors?].

PMID- 22852264
TI  - Discovering the 'heart of care'.

PMID- 22852266
TI  - Occupational medicine: making it work for you.

PMID- 22852265
TI  - Supreme decision.

PMID- 22852267
TI  - 6 keys to practicing multicultural medicine.

PMID- 22852268
TI  - Prepare your portfolio for retirement.

PMID- 22852269
TI  - Survey documents EHR implementation costs.

PMID- 22852270
TI  - Physicians offer advice as they prepare for implementation.

PMID- 22852271
TI  - What to expect when buying a practice.

PMID- 22852272
TI  - Defensive medicine: a culprit in spiking healthcare costs.

PMID- 22852273
TI  - [Vision "diabetes vaccine"].

PMID- 22852274
TI  - [Toll-like receptors: recognition receptors of the innate immune system and
      target structures for therapeutical intervention].
AB  - Toll-like receptors (TLR) are pattern recognition receptors of the innate immune
      system that recognize microbial ligands preferentially derived from bacteria and
      viruses. Activation of TLR results in an immediate pro-inflammatory response of
      the innate immune system. TLR located on the cell surface recognize bacterial
      cell wall components, while intracellular TLR recognize viral or bacterial
      nucleic acids. Due to their stimulatory activity, TLR ligands can act as
      adjuvants for vaccine development but are also used for local immunotherapy of
      certain types of skin lesions. On the other hand, TLR ligand antagonists are
      under development as an approach to dampen excessive innate immune responses.

PMID- 22852275
TI  - [Clinically significant drug-drug interactions between analgesics and
      psychotopics].
AB  - Combining analgesic and psychotropic drugs can lead to pharmacodynamic and
      pharmacokinetic drug interactions. Under treatment with several serotonergic
      substances serotonin syndrome can occur, e.g., with certain opioids and
      antidepressant drugs. Serotonin reuptake inhibitors also affect the serotonin
      level in platelets, this can raise the risk for gastrointestinal bleeding
      especially in combination with non-steroidal antirheumatic drugs. Anticholinergic
      effects and sedation are common side effects of psychotropic but also analgesic
      drugs with possible additive results. A wide range of interactions between
      analgesics and psychotropics can occure during metabolism, especially via the
      cytochrome-P-system. The clinical relevance of warnings on drug interactions from
      data banks has always to be judged for the individual patient.

PMID- 22852276
TI  - Early signals.

PMID- 22852277
TI  - Belatacept.
AB  - Immunosuppressive therapy designed to prevent kidney graft rejection usually
      consists of a triple-drug combination including a corticosteroid, a calcineurin
      inhibitor (ciclosporin or tacrolimus) and a drug that inhibits cell proliferation
      (azathioprine or mycophenolate mofetil). Belatacept is closely related to
      abatacept, an immunosuppressant marketed for rheumatic diseases. It is now
      authorised in the European Union for the prevention of kidney graft rejection, as
      a replacement for the calcineurin inhibitor. Two randomised controlled trials
      compared belatacept (2 doses) versus ciclosporin as part of the immunosuppressive
      regimen in respectively 666 and 534 patients. After 3 years of follow-up,
      survival with a functioning graft did not differ between the groups (about 80% in
      the trial closest to European protocols). Only the use of a high dose of
      belatacept instead of ciclosporin resulted in better preservation of renal
      function, but this is not the authorised dose. Lymphomas, particularly those
      affecting the central nervous system, were more frequent with belatacept in both
      trials (1.4% versus 0.9%). The risk was particularly high in patients receiving
      the high dose of belatacept, and in patients who were seronegative for Epstein
      Barr virus. Overall, the risk of infections seems to be similar with belatacept
      and ciclosporin, but certain severe infections were more frequent with
      belatacept, including progressive multifocal leukoencephalopathy and
      tuberculosis. Unlike ciclosporin, belatacept plasma concentrations do not need to
      be monitored. However, intravenous belatacept administration is less convenient
      than oral ciclosporin administration, especially during long-term treatment.
      Overall, it is better to continue to use ciclosporin, a better-documented drug,
      as part of immunosuppressive therapy after kidney transplantation.

PMID- 22852278
TI  - INN common stem: -piprazole.

PMID- 22852279
TI  - Aliskiren: negative trial data.

PMID- 22852280
TI  - Flurbiprofen without a prescription for dysmenorrhoea: rejected by French Health
      Products Agency.

PMID- 22852281
TI  - Sildenafil and pulmonary hypertension in children.

PMID- 22852282
TI  - Topical fluticasone for infants from 3 months of age.

PMID- 22852283
TI  - A poor example.

PMID- 22852284
TI  - Amlodidine + aliskiren.

PMID- 22852285
TI  - Naproxcinod.

PMID- 22852286
TI  - Pioglitazone: European approval maintained despite the acknowledged risks.

PMID- 22852287
TI  - Calcium channel blockers + macrolides: elderly patients hospitalised for low
      blood pressure.
AB  - Macrolides that inhibit cytochrome P450 isoenzyme CYP 3A4 can lead to the
      accumulation of calcium channel blockers metabolised by the same isoenzyme and
      therefore an increase in their dose-related adverse effects. A Canadian case
      control study examined the relationship between macrolide use and hospitalisation
      for hypotension (including shock) among 7100 elderly patients who were also
      taking a calcium channel blocker. The results showed more exposure to certain
      macrolides immediately prior to hospitalisation for hypotension than during an
      earlier control period; these macrolides included erythromycin (odds ratio (OR) =
      5.8; 95% confidence interval: 2.3 to 15) and clarithromycin (OR = 3.7, 95% CI:
      2.3 to 6.1). No such increase was found with azithromycin. In practice, patients
      treated with a calcium channel blocker should not be prescribed erythromycin or
      clarithromycin, but rather an antibiotic with similar efficacy but a lower risk
      of interaction.

PMID- 22852288
TI  - Domperidone: ventricular arrhythmia and sudden death (continued).
AB  - Domperidone, a "hidden" neuroleptic, is used for symptomatic treatment of
      gastroesophageal reflux disease, despite its uncertain efficacy. The intravenous
      form was withdrawn from the market in the 1980s following deaths due to cardiac
      arrhythmias. QT prolongation leading to cardiac arrhythmias, including life
      threatening torsades de pointes, has also been attributed to oral domperidone. In
      2010, two case-control studies, one Canadian and one Dutch, showed that patients
      who died suddenly or had severe ventricular arrhythmias were statistically
      significantly more likely than controls to have been exposed to domperidone. In
      practice, given its uncertain efficacy and a disproportionate risk of sudden
      death and severe ventricular arrhythmia, domperidone should not be used.

PMID- 22852289
TI  - Alcohol-based hand sanitizers: severe intoxication in children.
AB  - Alcohol-based hand sanitizers are an alternative to hand washing with soap and
      water when water is unavailable. Their use has increased over the last decade.
      Cases of acute intoxication have been reported in children after accidental
      ingestion of alcohol-based hand sanitizers, sometimes leading to inebriation,
      agitation, drowsiness, impaired consciousness, and blood alcohol levels sometimes
      exceeding 2 g/I. In practice, alcohol-based hand sanitizers should be kept out of
      reach of children and should only be used when hand washing with soap and water
      is not possible. The possibility of alcohol intoxication should be borne in mind
      when a child suddenly presents with behaviour problems or altered consciousness.

PMID- 22852290
TI  - NSAIDs: miscarriage.

PMID- 22852291
TI  - Vitamin E and prostate cancer.

PMID- 22852292
TI  - Fluoroquinolones and tendon disorders: even after single-dose therapy.

PMID- 22852293
TI  - Paracetamol during pregnancy: no particular danger for the child.
AB  - When a pregnant woman suffers from mild to moderate pain, and when simple non
      drug measures are ineffective, paracetamol is the drug of first choice. Data from
      epidemiological and animal studies are reassuring regarding the risk of
      malformations. In late 2010, a link was suggested between paracetamol exposure in
      utero and the occurrence of cryptorchidism, a common male urogenital birth defect
      that usually resolves during the first year of life. Does paracetamol exposure in
      utero increase the risk of birth defects, particularly cryptorchidism persisting
      beyond one year of age? To answer this question, we conducted a review of the
      literature using the standard Prescrire methodology. The results of about 10
      animal teratogenicity studies are reassuring. Some studies yielded conflicting
      results for testicular abnormalities. Two cohort studies including a total of
      nearly 49 000 boys showed no increase in the risk of persistent cryptorchidism
      after paracetamol exposure in utero. A case-control study showed a link with
      cryptorchidism in a subgroup of boys exposed to paracetamol in utero for more
      than 15 days; the analysis was not performed in boys with persistent
      cryptorchidism. Six cohort studies and 11 case-control studies including
      approximately 38 000 women showed no increase in malformations among children
      exposed to paracetamol in utero compared to unexposed children. Available data
      show no conclusive link between paracetamol exposure in utero and the risk of
      childhood asthma. Overall, data available in early 2012, especially those from
      epidemiological studies, are reassuring on the use of paracetamol during
      pregnancy. Paracetamol remains the analgesic and antipyretic medication of first
      choice for pregnant women when nondrug measures are ineffective.

PMID- 22852294
TI  - Paracetamol exposure in utero or during infancy: no increase in asthma.
AB  - The increasing incidence of asthma among children, and the increase in
      paracetamol exposure, suggested a possible link between the two. Most relevant
      data concern wheezing episodes in infants rather than asthma. About 20
      epidemiological studies have been published. Due to numerous biases, particularly
      the possible link between the use of paracetamol and respiratory disorders that
      preceded the diagnosis of asthma, these studies fail to show that paracetamol
      exposure in utero or during the first year of life causes persistent asthma.
      These data do not challenge the known harm-benefit balance of paracetamol during
      pregnancy and infancy. Paracetamol remains the analgesic and antipyretic drug of
      choice in both situations.

PMID- 22852295
TI  - Corporate influence over clinical research: considering the alternatives.
AB  - The dominant business model of the pharmaceutical sector is based on the massive
      promotion of drugs that often do not represent any significant therapeutic
      advance. Clinical research is therefore run like a promotional campaign. The data
      obtained from clinical research are primarily used to boost and support sales
      rather than to improve prescribing behaviour. Three common and widely used
      corporate strategies are used to this end: ghostwriters are employed to inflate
      the number of publications showing the drug in a positive light; results that
      would harm sales are not published (publication bias); and negative data are
      suppressed, sometimes going as far as to intimidate troublesome independent
      academics and whistle-blowers. The objective of these strategies is to enable the
      new drug to gain market share from its competitors. If medicine is to progress,
      research must be more independent and freed from the commercial imperatives of
      the pharmaceutical industry.

PMID- 22852296
TI  - The exorbitant price of cancer drugs.

PMID- 22852297
TI  - Influential role of nurses in healthcare reform.

PMID- 22852298
TI  - Structure and rheology of charge-free reverse micelles in aromatic liquid
      phenyloctane.
AB  - Reverse micelles formulation requires an inclusion of water or other polar
      molecules in the binary mixture of ionic surfactant and oil and generally exhibit
      spheroid geometry with a small aggregation number. Here, we report structure and
      rheology of charge-free (nonionic) reverse micelles in surfactant/oil systems. We
      have systematically investigated intrinsic parameters for the shape, size, and
      internal cross section structure control of such micelles using small-angle X-ray
      scattering (SAXS) and the rheometry. We found that diglycerol monomyristate
      (C14G2) when added into an aromatic organic liquid phenyloctane, spontaneously
      self-assembles into spheroid micelles with maximum diameter ca. 6.7 nm. Decrease
      in surfactant chain length favors globular-to-rod type transition and micellar
      aggregation number (N(agg)) increases significantly. On the other hand, increase
      in surfactant weight fraction induces one-dimensional (1-D) micellar growth;
      N(agg) increases in parallel to the surfactant concentration. Reverse micelles
      shrink with the rise of temperature, which is close to the rod-to-sphere type
      transition. However, water causes a significant micellar growth; N(agg) increases
      drastically, which shows that water not only increase reverse micellar size but
      also increases the number of surfactant molecules per micelle. All these
      microstructure transitions could be understood in terms of the modification of
      the critical packing parameter (cpp). The SAXS results are very well supported by
      the geometrical model fittings and rheometry.

PMID- 22852299
TI  - Structural characterizations of diglycerol monomyristate reverse micelles in
      aromatic solvent ethylbenzene.
AB  - Using small-angle X-ray scattering (SAXS) we have investigated the shape and size
      of diglycerol monomyristate (designated as C14G2) nonionic surfactant reverse
      micelles in aromatic solvent ethylbenzene as a function of surfactant
      concentration, temperature, and water. When C14G2 is added into ethylbenzene
      globular type reverse micelles with maximum core diameter ca. 4.5 nm are formed
      under ambient conditions. The micellar structure (shape and size) did not change
      with the surfactant concentration. However, an increase in temperature decreased
      the micellar size due to an increase in the critical packing parameter (cpp).
      Surfactant becomes more lipophilic upon heating and the micellar curvature tends
      to become more negative at higher temperature. Addition of a small amount of
      water caused a significant micellar growth. For instance, incorporation of 0.3%
      water in the 5% C14G2/ethylbenzene system resulted in the formation of 2.1 time
      bigger micelles with a small water pool in the micellar core. Besides the
      micellar shape is modified into an ellipsoidal prolate, whose scenario can be
      understood in terms of hydration of the surfactant's headgroup. Hydration
      decreases the cpp and favors micellar growth. An increase of temperature of a
      water incorporated system decreased the micellar size due to dehydration, which
      is equivalent to rod-to-sphere type transition.

PMID- 22852300
TI  - The influence of the organic/inorganic interface on the organic-inorganic hybrid
      solar cells.
AB  - Organic-inorganic hybrid solar cells based on poly(3-hexylthiophene) (P3HT) and
      (6,6)-phenyl C61 butyric acid methyl ester (PCBM) hybridized with ZnO nanorods
      were fabricated by growing vertical ZnO nanorods on indium tin oxide (ITO)
      substrates and filling with bulk heterojunction polymers (P3HT:PCBM). The
      interface between the organic and inorganic nanostructures influences the
      performance of the organic-inorganic hybrid solar cells. In this paper, the
      influence of the state of the P3HT:PCBM/ZnO interface on the performance of
      organic-inorganic hybrid solar cells is examined. The solar cell performance was
      high when the P3HT:PCBM/ZnO junction area was large. The charge separation is
      effective when the active layer/electron transport layer junction area is large,
      resulting in increasing photocurrent and a high conversion efficiency. The bulk
      heterojunction polymer concentration was kept low to infiltrate into the ZnO
      nanorods, resulting in a large active layer/electron transport layer junction
      area.

PMID- 22852301
TI  - Rapid synthesis of low-fractal dimension titanium oxide polymers by a sol-gel
      technique using hydrazine monohydrochloride.
AB  - Titanium oxide polymers having a low-fractal dimension (d(f) < 2) were rapidly
      synthesized from titanium tetra-n-butoxide via a catalytic sol-gel process with a
      hydrazine monohydrochloride catalyst. Different from conventional sol-gel
      processes aimed at producing low-fractal dimension titanium oxide polymers, the
      present synthetic strategy needed neither organic ligand to enhance the stability
      of titanium alkoxides nor an extremely long reaction time in a strongly acidic
      solution condition, thanks to a drastically accelerated polycondensation
      reaction. We pursued the structure evolution of the titanium oxide polymers by
      means of time-resolved small-angle X-ray scattering (Tr-SAXS). The SAXS data
      unambiguously demonstrate the generation of the expanded polymer-like structure
      characterized by the fractal dimension of d(f) approximately equal 5/3. The
      results offer an efficient route to the synthesis of the weakly-branched titanium
      oxide polymers, which are expected to be used to create a wide range of optical
      materials having a high refractive index, such as anti-glare coating.

PMID- 22852302
TI  - Functionalization of multi-walled carbon nanotubes with bis(2,2':6',2"
      terpyridine) ruthenium(II)-connected diblock polymer.
AB  - Multi-walled carbon nanotubes (MWCNTs) were functionalized with a bis(2,2':6',2"
      terpyridine) ruthenium(ll)-connected diblock poly(N-isopropyacryamide)
      (RuTpyPNIPAM) by a simple methodology of covalent amidation. The composition and
      structure of the functionalized ruthenium multi-walled carbon nanotubes
      (RuMWCNTs) were characterized by thermogravimetric analysis, Fourier transform
      infrared spectroscopy (FTIR), Raman spectroscopy and scanning electron microscopy
      (SEM). These characterization methods confirm that after functionalization,
      ruthenium metallopolymer are interconnected or attached as aggregated structures
      on the surface of the carbon nanotubes.

PMID- 22852303
TI  - Preparation and optimization of epitaxial growth of transparent ZnO nanotip thin
      films by hydrothermal method.
AB  - Zinc oxide (ZnO) nanotip thin films were prepared on ZnO coated nanocrystalline
      ITO/glass substrates by hydrothermal method. In order to obtain the ZnO nanotip
      arrays with high aspect ratio, the experimental conditions were optimized. The
      scanning electron microscope images showed that the surface morphology of ZnO
      thin films could be easily manipulated by changing the seed layer thickness and
      growth time. The ZnO nanotip thin films were grown epitaxially on ZnO seed layer
      coated ITO/glass substrates. The surface morphology of ZnO thin films on
      ITO/glass substrate changed from nanorods with a flat-top end to nanotips as the
      growth time was increased from 3 to 15 h. The ZnO thin films prepared under these
      deposition conditions were highly oriented along (002) direction. The as-prepared
      sample (15 h) was annealed at different temperatures (30, 100, 150, and 270
      degrees C). The surface morphologies of annealed ZnO thin films did not show any
      remarkable change and the best crystallinity was observed at 100 degrees C. The
      photoluminescence spectra showed that the near band edge emission shifted to
      shorter wavelength as the annealing temperature was increased from 30 to 270
      degrees C, it was due to the intrinsic stress in the films. This was confirmed by
      X-ray diffraction analyses. NPB thin films were prepared on ITO/clay and
      ITO/glass substrates by thermal evaporation method. The electrical properties of
      Ag/NPB/ITO/Clay showed the Ohmic characteristics (J proportional V(1.0)). The J-V
      characteristic of Ag/NPB/PMMA/ZnO/ITO/Glass showed good rectification behaviour
      with a diode-ideality factor of 1.36.

PMID- 22852304
TI  - Microstructural and optical characterization of TiO2 doped with ytterbium
      synthesized by sol-gel and Solar physical vapor deposition process.
AB  - Pure and ytterbium doped TiO2 nanopowders in anatase phase have been prepared by
      sol-gel method (SGM) and Solar Physical Vapour Deposition process (SPVD). The
      physico-chemical parameters of the nanopowders have been described based on the
      results of micro-structural characterization performed by X-ray diffractometry,
      scanning electron microscopy, atomic force microscopy, and nitrogen sorption
      measurements. Thus, final micro-structural properties of SGM and SPVD titania
      nanopowders have been compared in detail revealing significant changes in the
      structure and morphology of these two types of materials. Addition of ytterbium
      had no significant effect on above-mentioned properties, although it modifies
      significantly the optical properties of the investigated materials. The
      luminescent properties of developed material were found to be comparable to bulk
      oxide materials and better than these reported earlier for ytterbium doped
      titania. In particular it has been shown that the luminescence of SPVD
      nanopowders is significantly stronger than this of SGM samples.

PMID- 22852305
TI  - Synthesis and characterization of dextran-capped silver nanoparticles with
      enhanced antibacterial activity.
AB  - Dextran-capped silver nanoparticles were synthesized by reducing silver nitrate
      with NaBH4 in the presence of dextran as capping agent. The characters of silver
      nanoparticles were investigated using UV-Vis spectrophotometer, nano-grainsize
      analyzer, X-ray diffraction, and transmission electron microscopy. Results showed
      that the silver nanoparticles capped with dextran were in uniform shape and
      narrow size distribution. Moreover, compared with polyvinylpyrrolidone (PVP)
      capped silver nanoparticles, the dextran-capped ones possessed better stability.
      Antibacterial tests of these silver nanoparticles were carried out for
      Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas
      aeruginosa, and Klebsiella pneumoniae. Results suggested that the dextran-capped
      silver nanoparticles had high antibacterial activity against both Gram-positive
      and Gram-negative bacteria. In addition, the cytotoxicity in vitro of the dextran
      capped silver nanoparticles was investigated using mouse fibrosarcoma cells
      (L929). The toxicity was evaluated by the changes of cell morphology and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Results indicated
      that these silver nanoparticles had slight effect on the survival and
      proliferation of L-929 cells at their minimal inhibitory concentration (MIC).
      After modified by dextran, the physiochemical properties of the silver
      nanoparticles had been improved. We anticipated that these dextran-capped silver
      nanoparticles could be integrated into systems for biological and pharmaceutical
      applications.

PMID- 22852306
TI  - Carbon nanocapsules as an effective sensing platform for fluorescence-enhanced
      nucleic acid detection.
AB  - In this communication, we demonstrate the proof of concept that carbon
      nanocapsules (CNCs) can be used as an effective fluorescent sensing platform for
      nucleic acid detection with selectivity down to single-base mismatch. The
      detection is accomplished by two steps: (1) CNC adsorbs and quenches the
      fluorescence of the dye-labeled single-stranded DNA (ssDNA) probe; (2) in the
      presence of the target, a hybridization event occurs, which produces a double
      stranded DNA (dsDNA) that detaches from the CNC surface, leading to recovery of
      the dye fluorescence.

PMID- 22852307
TI  - An efficient one pot synthesis of water-dispersible calix[4]arene polyhydrazide
      protected gold nanoparticles--a "turn off" fluorescent sensor for Hg[II] ions.
AB  - In the present study, we report the synthesis of aqueous stable gold
      nanoparticles by using calix[4]arene polyhydrazide (CPH) as both reducing and
      capping agents. The calix[4]arene polyhydrazide reduced gold nanoparticles (CPH
      AuNps) were characterized by UV/Vis, particle size analyzer (PSA) and
      transmission electron mictroscopy (TEM). The records confirmed high stability of
      CPH-AuNps in aqueous solution over a long period of time and even at varied pH.
      Additionally, CPH-AuNps have been investigated for its application as "Turn Off"
      fluorescent sensor for Hg[II]. A concentration of Hg[II] in the limit of 10 nM to
      10 microM can be detected based on fluorescence quenching of the CPH-AuNPs and it
      was also concluded from the spectroscopic data that CPH-AuNPs possess excellent
      selectivity to Hg[II] over several metal ions like Pb[II], Cu[II], Cd[II],
      Mn[II], Zn[II] and Ni[II].

PMID- 22852308
TI  - Field emission and photo-catalytic investigations on hierarchical nanostructures
      of copper doped CdS synthesized by kitchen-chemistry approach.
AB  - We herein report an economical and facile technique for the synthesis of
      hierarchical nanostructures of Cu doped CdS nanostructures by microwave assisted
      solvothermal technique using a household microwave oven. We attempted to
      establish the effect of variation of solvents ratio on the morphological and
      optical properties of the obtained nanoscale structures. The field emission
      characteristics of the copper doped CdS nanoarchitecture have been studied and
      the turn on field is found to be 2.8 V/microm for an emission current density of
      approximately 0.1 microA/cm2. Emission current stability is determined at the
      preset current of approximately 1 microA and approximately 10 microA for the
      stable duration of approximately 4 hrs. The observed field emission results
      envisage the possibility of using the present emitter in the field emission
      sources. We believe that this is a unique report on the synthesis as well as
      field emission studies of copper doped CdS nanostructures. Photocatalytic dye
      degradation ability of the Cu doped CdS nanostructures is observed to be less
      than the undoped CdS counterparts.

PMID- 22852309
TI  - Preparation and characterization of visible-light-driven TiO2 photocatalyst Co
      doped with nitrogen and erbium.
AB  - A series of nitrogen and erbium co-doped TiO2 photocatalyst was prepared by sol
      hydrothermal method. The structure and properties of the photocatalyst were
      characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, X
      ray photoelectron spectroscopy (XPS), and UV-vis diffuse reflectance spectra
      (DRS). The XRD and BET results showed that co-doping inhibited the increase of
      crystallite size and enlarged specific surface areas. XPS spectroscopy indicated
      nitrogen atoms were incorporated into TiO2 lattice, and erbium atoms mostly
      existed in the forms of Er2O3. A shift of the absorption edge to the lower energy
      and four absorption bands located at 654, 544, 524 and 489 nm attributed to the
      4f transitions of 4I15/2 --> 4F2/9, 4I15/2 --> 4S3/2, 4I15/2 --> 2H11/2, 4I15/2 -
      > 4F7/2 of Er3+ were observed using DRS spectroscopy. The catalytic efficency was
      evaluated by the photocatalytic degradation of methyl orange (MO) under visible
      light irradiation. The results showed that the photocatalytic performance of the
      co-doped TiO2 was related with the hydrothermal temperature and the molar ratio
      of N/Ti, and they showed higher acitivites than pure TiO2. Results determined by
      fluorescence technique revealed that irradiation (lambda > 400 nm) of TiO2
      photocatalyst dispersed in MO solution induces the generation of the highly
      active hydroxyl radicals (OH). It indicated the photocatalytic activities of TiO2
      photocatalyst were correlation with the formation rate of hydroxyl radicals (OH)
      and other active oxygen species.

PMID- 22852310
TI  - Aqueous synthesis of highly monodispersed thiol-capped CdTe quantum dots through
      electrochemical approach.
AB  - A facile green approach has been developed to control the growth regime in the
      aqueous synthesis of CdTe semiconductor Quantum dots (QDs) via the
      electrochemistry method. The Low growth temperature and slow injection of Te
      precursors are used to prolong the diffusion controlled stage and thus suppress
      Ostwald ripening during nanocrystal growth. The experimental results showed that
      a low concentration of Te precursor would definitely influence the growth
      procedure. The narrow absorption peaks in the UV-visible absorption spectra, as
      well as transmission electron microscopy images indicated that the as-prepared
      CdTe QDs had a good monodispersity. The high-resolution transmission electron
      microscopy (HRTEM) images and powder X-ray diffraction (XRD) pattern suggested
      that the as-prepared QDs have high crystallinity and cubic structure. The QDs
      exhibited high fluorescence QYs about 50% and the best of QY 67% without any
      postpreparative treatment over a broad spectral range of 516-609 nm, which could
      be further broadened by long-term refluxing. The current work suggested that
      electrochemical method was an attractive approach to the synthesis of high
      quality II-VI semiconductor QDs at a large scale.

PMID- 22852311
TI  - Modified solid-state reaction synthesized cathode lithium iron phosphate
      (LiFePO4) from different phosphate sources.
AB  - A modified solid-state method was used to prepare LiFePO4. With the aid of
      deionized water, a mixture containing Fe2O3, NH4H2PO4 (or (NH4)2HPO4), LiOH,
      glucose and oxalic acid was prepared into fluffy powders, which were heated in a
      carbon-coated crucible at 700 degrees C for 3 hours to synthesize LiFePO4 without
      any inert gas flow. For the first time, the roles of NH4H2PO4 and (NH4)2HPO4 on
      the preparation of LiFePO4 were systematically investigated. The obtained samples
      were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM)
      and energy dispersive spectroscopy (EDS), revealing that the crystallinity of the
      LiFePO4 sample prepared from NH4H2PO4 is superior to that prepared from
      (NH4)2HPO4 and the particle size of the sample prepared from NH4H2PO4 is smaller
      than that prepared from (NH4)2HPO4. The specific capacity, cycle property and
      rate capabilities were also compared between the as-prepared LiFePO4 samples. A
      better electrochemical performance was observed in the sample prepared from
      NH4H2PO4.

PMID- 22852312
TI  - Effect of single-walled carbon nanotubes on Bacillus anthracis cell growth,
      sporulation, and spore germination.
AB  - In this study, the effect of single-walled carbon nanotubes (SWCNTs) on B.
      anthracis cell growth, spore formation, and spore germination was studied. We
      found that SWCNTs at a concentration of 100 microg/ml exhibited obvious
      antimicrobial activity on 10(6) cfu/ml B. anthracis cells. At 300 microg/ml, 1 h
      of SWCNTs treatment could inactivate B. anthracis cells by approximately 2 log
      viable cell reduction. The SWCNT treatment did not induce spore formation. We
      also found that SWCNTs were not effective in the inactivation of B. anthracis
      spores at concentrations from 50 microg/ml up to 300 microg/ml. Fluorescence
      microscopy and scanning electron microscopy were used to examine the interactions
      between SWCNTs and B. anthracis cells/spores. Analysis of these microscopic
      images suggested that the direct contact between SWCNTs and B. anthracis cells
      lead to cell membrane damage and the inactivation of cells, whereas the lack of
      tight direct contact between SWCNTs and spores was the reason accounting for its
      ineffectiveness in inactivating spores.

PMID- 22852313
TI  - Effect of MoO3 on the synthesis of boron nitride nanotubes over Fe and Ni
      catalysts.
AB  - Synthesis of boron nitride nanotubes at reduced temperature is important for
      industrial manufactures. In this study boron nitride nanotubes were synthesized
      by thermal evaporation method using B/Fe2O3/MoO3 and B/Ni2O3/MoO3 mixtures
      separately with ammonia as the nitrogen source. The growth of boron nitride
      nanotubes occurred at 1100 degrees C, which was relatively lower than other metal
      oxides assisted growth processes requiring higher than 1200 degrees C. MoO3
      promoted formation of B2O2 and aided boron nitride nanotubes growth at a reduced
      temperature. The boron nitride nanotubes with bamboo shaped, nested cone
      structured and straight tubes like forms were evident from the high resolution
      transmission electron microscopy. Metallic Fe and Ni, formed during the process,
      were the catalysts for the growth of boron nitride nanotubes. Their formation was
      established by X-ray diffraction. FT Raman showed a peak due to B-N vibration of
      BNNTs close to 1370 cm(-1). Hence MoO3 assisted growth of boron nitride nanotubes
      is advantageous, as it significantly reduced the synthesis temperature.

PMID- 22852314
TI  - A complementary electrochromic device with highly improved performance based on
      brick-like hydrated tungsten trioxide film.
AB  - Uniform and well adhesive nanostructured hydrated tungsten trioxide (3WO3 x H2O)
      films were grown on fluorine doped tin oxide (FTO) substrate via a facile and
      template-free crystal-seed-assisted hydrothermal method by addition of ammonium
      sulfate ((NH4)2SO4) and hydrogen peroxide (H2O2). X-ray diffraction (XRD) studies
      indicated that the films are of orthorhombic structure. Scanning electron
      microscopy (SEM) and high resolution transmission electron microscopy (HRTEM)
      analysis showed that the film was composed of brick-like nanostructures with a
      preferred growing direction along (002). The influence of seed layer, (NH4)2SO4
      and H2O2 on the products were also studied. The film showed good cyclic
      stability, comparable switching speed and coloration efficiency (30.1 cm2 C(-1)).
      A complementary electrochromic device based on the film and Prussian blue
      depicted highly improved color contrast, coloration/bleaching response (1.8 and
      3.7 s respectively) and coloration efficiency (164.6 cm2 C(-1)).

PMID- 22852315
TI  - Capacitance distribution of Ni-Nb-Zr-H glassy alloys.
AB  - Capacitance distribution of {(Ni(0.6)Nb(0.4)(1-x)Zrx}(100-y)-Hy (x = 0.30, 0.35,
      0.40, 0.45 and 0.50, 0 < or = y < or = 20) glassy alloy ribbons was carried out
      by ac impedance analysis at frequency of 1 kHz, in terms of a distributed
      constant equivalent circuit. The capacitance can be represented by oblique
      contour lines. The highest capacitance (1-11 microF) could be found near the
      point when x = 0.40, y = 10, which is a composition occurring room-temperature
      Coulomb oscillation, while capacitance of the composition (x = 0.35, y = 4)
      occurring ballistic transport was around 0.8 microF. The capacitance difference
      would be explained by an effect of hydrogen localization derived from morphology
      of distorted Zr-centered icosahedral Zr5Ni5Nb3 clusters and ideal Ni-centered
      clusters. The electrocapillarity equation showed that the specific capacitance
      between two electrodes increases parabolic with decreasing the distance, as a
      polarized glutinous liquid.

PMID- 22852316
TI  - Fabrication of dielectric nanocubes in ordered structure by capillary force
      assisted self-assembly method and their piezoresponse properties.
AB  - Ordered structures of barium titanate (BT) nanocubes, strontium titanate (ST)
      nanocubes and BT/ST nanocubes mixture were directly fabricated on Si and Pt
      coated Si substrates using a capillary force assisted assembly method. The
      morphology of self-assembled structures was observed using field emission
      scanning electron microscopy (FE-SEM) and scanning probe microscopy (SPM). It was
      revealed that nanocubes were arranged with various degrees of ordering to develop
      multilayer and monolayer regions at the surface of substrates. The elemental
      mapping of the structure consisting of the nanocubes mixture was also
      investigated by transmission electron microscopy (TEM) with an energy dispersive
      X-ray spectroscopy (EDX). It was revealed that BT and ST nanocubes coexisted
      homogeneously in the structure and had possibility to be arranged in order to
      each other. The piezoresponse properties obtained by scanning probe microscopy
      (SPM) indicated that the hetero-interface between BT and ST nanocubes would
      introduce anomaly in piezoelectric properties.

PMID- 22852317
TI  - Conditions of polymerase chain reaction amplification by magnetic enrichment and
      nanoscale detection sensitivity.
AB  - In this research, we reported a method of polymerase chain reaction (PCR)
      amplification by means of magnetic enrichment. First, after denaturation, the
      target sequence was combined with biotin-modified specific primer through
      hybridization and enriched at the surface of gamma-Fe2O3 by biotin-avidin special
      interaction. Then single target sequence was gained through denaturation, and
      general PCR amplification was performed. The experiment conditions such as the
      hybridization temperature between target sequence and biotin-modified specific
      primer, and the dosage of magnetic nanoparticles gamma-Fe2O3 were optimized.
      Finally, the sensitivity of the method was checked. The lowest concentration of
      target sequence was detected as low as 5 x 10(-7) ng/mL. This simple method could
      provide a quick and early diagnosis of malignant infectious diseases such as
      SARS, avian flu and swine flu etc., that occur occasionally nowadays.

PMID- 22852318
TI  - Facile synthesis of multifunctional ZnFe2O4 nanoparticles in liquid polyols.
AB  - Monodisperse water-soluble ZnFe2O4 nanoparticles with the particle size of 6.3 nm
      and band gap of 2.04 eV were synthesized by a simple and inexpensive method based
      on a polyols method. The products were characterized by X-ray powder diffraction
      (XRD), transmission electron microscopy (TEM), UV-vis absorption
      spectrophotometer, Fourier transform infrared (FT-IR) spectrometer, fluorescence
      spectrometer, X-ray photoemission spectroscopy (XPS) and physical properties
      measurement system (PPMS). The ZnFe2O4 nanoparticles display photoluminescence
      and exhibit excellent superparamagnetic properties at room temperature.
      Photocatalytic activity studies confirm the as-synthesized ZnFe2O4 nanoparticles
      have photoactive property towards the photodegradeation of methyl orange in the
      aqueous solution. The photodecomposition rate of ZnFe2O4 nanoparticles maintains
      the high value for the second time by retrieving the catalyst using the magnet.
      Thus, the multifunctional ZnFe2O4 nanoparticles can be not only used in the
      biological application, but also served as recyclable photocatalysts.

PMID- 22852319
TI  - Fluorescence enhancement using silver nanotriangle arrays.
AB  - We describe the fabrication of silver nanotriangle array using angle resolved
      nanosphere lithography and utilizing the same for enhancing fluorescence. The
      well established nanosphere lithography is modified by changing the angle of
      deposition between the nanosphere mask and the beam of silver being deposited
      resulting in nanotriangles of varying surface area and density. The 470 nm
      plasmon resonance wavelength of the substrate was determined using minimum
      reflectivity method which closely matches with excitation wavelength of the
      fluorophore. Ten times enhancement in fluorescence emission intensity is obtained
      from fluorescein isothiocyanate coated on top of silver nanotriangle array
      separated by a spacer layer of poly vinyl alcohol as compared to glass. The
      enhanced fluorescence emission is attributed to the increase in local field
      enhancement.

PMID- 22852320
TI  - UV induced zener diode characteristic in a single n-ZnO/p++-Si
      nanoheterojunction.
AB  - Rectification is observed in a single n-ZnO/p++-Si nanoheterojunction using ultra
      high vacuum compatible scanning tunneling microscope. The nanohetrojunctions have
      been grown using catalyst free vapor-solid growth of ZnO nanorods on p++-Si
      substarte. A high rectification ratio approximately 100 at 2 V is observed in the
      current voltage measurements. Temperature dependent study in these nanohetero
      junctions showed activation energy for carrier conduction approximately 66 meV,
      which is primarily associated to the presence of heterojunction induced interface
      states. Role of ultra violet excitation on these finite sized (approximately 500
      nm) nanoheterojunction is also studied with photo-generated electron-hole pairs.
      A Zener breakdown is observed in this photo-excitation process. Increase in the
      concentration of minority carriers and corresponding decrease in barrier width
      and height at the junction have been identified for the observed tunneling
      behavior under UV illumination. The large carrier concentration in the finite
      sized device with large diffusion length of electron (approximately 2 microm) is
      made responsible for the observed voltage regulation.

PMID- 22852322
TI  - Enhancing stability and photocatalytic activity of ZnO nanoparticles by surface
      modification of graphene oxide.
AB  - This work reports a simple method for the preparation of high-quality GO-ZnO
      nanocomposite materials. Transmission electron microscopy (TEM) revealed that the
      ZnO nanoparticles are uniformly distributed on the GO sheets and the diameter of
      the ZnO nanoparticles falls in 5-8 nm. Further experimental results imply that
      involving GO sheets into the system could remarkably prevent the aggregation of
      ZnO nanoparticles compared to pure ZnO. The photocatalytic activity and stability
      of the prepared GO-ZnO composite for the degradation of Acid Orange 7 (AO 7)
      under UV light irradiation is significantly enhanced in comparison to the as
      synthesized pristine ZnO nanoparticles. Considering the high photocatalytic
      acitivity and relative stability, this high-quality GO-ZnO nanocomposite is
      beneficial for the applications in environmental engineering and other fields.

PMID- 22852321
TI  - Antibacterial activity and increased freeze-drying stability of sialyllactose
      reduced silver nanoparticles using sucrose and trehalose.
AB  - The resistance to current antibiotics results in the emergence of health
      threatening bacteria. Silver nanoparticles are known to exhibit broad-spectrum
      antibacterial activities without the development of resistance. Herein, we
      developed a green synthetic method for the preparation of silver nanoparticles
      with sialyllactose instead of toxic chemicals as a reducing agent, which would
      improve its therapeutic applicability and increase its biocompatibility. Oven
      incubation, autoclaving and microwave irradiation methods were applied to prepare
      the silver nanoparticles. High resolution-transmission electron microscopy and
      atomic force microscopy images revealed mostly spherical and amorphous silver
      nanoparticles with an average diameter of 23.64 nm. Fourier Transform-infrared
      spectra suggest that the N-H amide of sialyllactose might be involved in the
      binding of silver nanoparticles. Based on thermogravimetric analyses, 2,3
      sialyllactose-reduced silver nanoparticles are composed of 54.3 wt% organic
      components and 45.7 wt% metallic silver. Enhanced antibacterial activities of
      silver nanoparticles (approximately 8-fold) were observed against Pseudomonas
      aeruginosa, Escherichia coli and Salmonella typhimurium (minimum inhibitory
      concentration 16 microg/mL). Next, we employed the use of carbohydrate
      stabilizers to increase the stability of silver nanoparticles during a freeze
      drying process. It was found that sucrose and trehalose were the most effective
      stabilizers. In addition, silver nanoparticles possessed excellent salt stability
      as well as on-the-shelf stability in the presence of these stabilizers.
      Derivatives of sialic acid are known to be anti-influenza agents; therefore, the
      newly prepared silver nanoparticles may serve as useful antibacterial and
      antiviral agents to cope with both pathogenic bacteria and viruses in the near
      future.

PMID- 22852323
TI  - Direct electrochemistry of Shewanella loihica PV-4 on gold nanoparticles-modified
      boron-doped diamond electrodes fabricated by layer-by-layer technique.
AB  - Microbial Fuel Cells (MFCs) are robust devices capable of taping biological
      energy, converting pollutants into electricity through renewable biomass. The
      fabrication of nanostructured electrodes with good bio- and electrochemical
      activity, play a profound role in promoting power generation of MFCs. Au
      nanoparticles (AuNPs)-modified Boron-Doped Diamond (BDD) electrodes are
      fabricated by layer-by-layer (LBL) self-assembly technique and used for the
      direct electrochemistry of Shewanella loihica PV-4 in an electrochemical cell.
      Experimental results show that the peak current densities generated on the Au/PAH
      multilayer-modified BDD electrodes increased from 1.25 to 2.93 microA/cm(-2) as
      the layer increased from 0 to 6. Different cell morphologies of S. loihica PV-4
      were also observed on the electrodes and the highest density of cells was
      attached on the (Au/PAH)6/BDD electrode with well-formed three-dimensional
      nanostructure. The electrochemistry of S. loihica PV-4 was enhanced on the
      (Au/PAH)4/BDD electrode due to the appropriate amount of AuNPsand thickness of
      PAH layer.

PMID- 22852324
TI  - Ultrasonication study for suspending single-walled carbon nanotubes in water.
AB  - A systematic calorimetry-based technique was developed to standardize single
      walled carbon nanotube (SWNT) dispersion protocol. Simple calorimetric
      experiments were performed to benchmark the performance of the ultra
      dismembrator. Temperature profiles for the sonication period were utilized to
      estimate energy input to the system. Energy loss profile was generated for the
      ultradismembrator in use and a calibration relationship was formulated that could
      standardize the sonication process. The standardized protocol was used to prepare
      aqueous SWNT suspensions-sonicating SWNTs in a varied range of input energy (18
      100 kJ) in water. SWNT mass fractions suspended for each energy input was
      accurately measured and the suspended SWNT samples were characterized for
      morphology, surface potential, cluster size and structure, and chemical
      functionality using high resolution transmission electron microscopy (HRTEM),
      electrophoresis, dynamic and static light scattering (DLS/SLS), and Raman
      spectroscopy. The study demonstrated that suspended mass of SWNTs increased up to
      18 kJ of energy input with no further increase upon continued energy input. The
      physicochemical properties showed similar trend for energy input. The aggregate
      cluster size, surface potential behavior, as well as the Raman defect properties
      plateaued after the initial energy input. The significant changes observed were
      limited to morphological properties, i.e., shorter length, debundled, and sharp
      edged SWNTs and fractal cluster formation (lower D(f)) with increased input
      energy.

PMID- 22852325
TI  - A novel method for large area graphene transfer on the polymer optical fiber.
AB  - We develop two simple methods-the dip coat stamping and lift-off methods-to
      transfer large area, high quality graphene films onto the top and side faces of
      the polymer optical fiber. The graphene films can be synthesized using chemical
      vapor deposition method on large Cu foils. After synthesis, the graphene films
      are characterized by scanning electron microscopy, atomic force microscopy and
      Raman spectroscopy. The polymer optical fiber probe with the transferred graphene
      film can be used as a chemical sensor for the detection of various organic
      aerosols.

PMID- 22852326
TI  - Removal of fluoride from water using iron oxide-hydroxide nanoparticles.
AB  - A novel and facile method for the synthesis of uniform stoichiometric powder form
      of non-magnetic iron oxide-hydroxide nanoparticles with spherical morphology and
      its application for defluoridation of drinking water is reported. X-ray powder
      diffraction analysis (XRD), BET surface area, FTIR, field emission scanning
      electron microscopy (FESEM) and Transmission electron microscopy (TEM) images
      were used to characterize nanoscale iron oxide-hydroxide. Transmission electron
      microscopy (TEM) image revealed the formation of iron oxide-hydroxide
      nanoparticles with spherical morphology. The iron oxide-hydroxide nanoparticles
      showed an excellent ability to remove fluoride (F-) from contaminated water over
      a wide range of pH. The influences of temperature, stirring speed, pH, adsorbent
      dose and contact time were studied. The equilibrium data were tested with various
      isotherm models and finally, a calculation procedure was reported for the
      calculation of adsorbent requirement. The fluoride adsorbed nanoparticles was
      regenerated upto 70% using sodium hydroxide or hydrochloric acid solution. The
      iron oxide-hydroxide nanoparticles can be used as an effective and replicable
      adsorbent media for defluoridation of water in presence of competing anions like
      chloride, iodate, iodide and sulphate.

PMID- 22852327
TI  - Synthesis and optoelectrochemical properties of ZnS:Mn nanocrystals.
AB  - Mn2+ ions doped ZnS semiconductor nanocrystals (ZnS:Mn NCs) were synthesized
      using colloidal chemical method at 70 degrees C without any capping agents. The
      as-prepared undoped ZnS and ZnS:Mn NCs were characterized by UV-Vis absorption
      spectra, fluorescent emission spectra, X-ray powder diffraction (XRD),
      inductively coupled plasma analysis (ICP), X-ray photoelectron spectroscopy
      (XPS), Dynamic light scattering (DLS), cyclic voltammogram and electronic
      transmission microscopy (TEM). The dependence of photoluminescence of ZnS:Mn NCs
      on dopant concentration was studied. The results show that Mn2+ ions mainly stay
      at ZnS nanocystal surface, and Mn2+-surface defect state complex was formed, as a
      result of which, surface defect emission of ZnS nanocrystals was substituted with
      Mn2+-related PL emission. The strongest fluorescent emission intensity was obtain
      at 1.85 at% Mn2+ doped ZnS:Mn NCs. The Mn2+ doped ZnS:Mn NCs are of 5 nm in
      diameter. The emission peak at 575 nm is attributed to d-d (4T1 --> 6A1)
      transition of Mn2+ ions. The existence of Mn2+-related photoluminescence could be
      well correlated with cyclic voltammogram of Mn2+-doped NCs, where pair of
      oxidation and reduction peaks were clearly observed due to the doped Mn2+ ions.
      The adsorbed Mn2+ ions on ZnS NCs produced neither Mn2+ emission nor redox peaks.
      For heavily doped ZnS:Mn NCs (4.87 at%), redox peaks gap in cyclic voltammogram
      became larger and new oxidation peak appeared. Correspondingly, when the Mn2+
      doping concentration reached 4.87 at%, the Mn2+-related emission totally
      disappears due to the Mn-Mn interactions. This work implys that electrochemical
      technique is possibly an useful tool to probe the local structure of doped Mn2+
      ions.

PMID- 22852328
TI  - Effects of surface potential on growth of ZnO nanorod arrays investigated by
      electric force microscopy.
AB  - The electric and Kelvin force probe microscopy were used to investigate the
      surface potentials on the ZnO seed layer, which shows a remarkable dependence on
      the annealing temperature. The optimum temperature for the growth of nanorod
      arrays normal to the surface was found to be at 600 degrees C, which is in the
      range of right surface potentials and energy measured between 500 degrees C and
      700 degrees C. We demonstrated from both electric and Kelvin force probe
      microscopy studies that surface potential controls the growth of ZnO nanorods,
      illustrating the fact that this is a promising technique to visualize the control
      of ZnO nanorod arrays by studying their surface potentials. This study will
      provide important understanding of growth of other nanostructures.

PMID- 22852329
TI  - Electrocatalytic reduction of H2O2 on thiolate graphene oxide covalently to
      bonded palladium nanoparticles.
AB  - The electrocatalytic reduction of hydrogen peroxide on thioalted graphene oxide
      (t-GO) covalent bonded to palladium nanoparticles was used as the basis of an
      H2O2 biosensor. Poly (diallydimethylammonium chloride)-coated t-GO-Pd on glassy
      carbon electrodes was easily and quickly prepared and gave sensitive measurements
      of H2O2 concentration. The Pd nanoparticles covalently bonded to the thiolated
      graphene oxide were characterized by transmission electron microscopy, X-ray
      photoelectron spectroscopy, and energy dispersive X-ray spectroscopy. Comparable
      results for H2O2 determination were obtained from cyclic voltammetric and
      amperometric measurements. The proposed H2O2 biosensor exhibited a wide linear
      range of 10 microM to 10 mM, and a low detection limit of 0.22 microM (S/N = 3),
      at an applied potential of -0.1 V by the amperometric method.

PMID- 22852330
TI  - Experimental and theoretical study of the optical and electrical properties of
      nanostructured indium tin oxide fabricated by oblique-angle deposition.
AB  - Oblique-angle deposition of indium tin oxide (ITO) is used to fabricate optical
      thin-film coatings with a porous, columnar nanostructure. Indium tin oxide is a
      material that is widely used in industrial applications because it is both
      optically transparent and electrically conductive. The ITO coatings are
      fabricated, using electron-beam evaporation, with a range of deposition angles
      between 0 degrees (normal incidence) and 80 degrees. As the deposition angle
      increases, we find that the porosity of the ITO film increases and the refractive
      index decreases. We measure the resistivity of the ITO film at each deposition
      angle, and find that as the porosity increases, the resistivity increases
      superlinearly. A new theoretical model is presented to describe the relationship
      between the ITO film's resistivity and its porosity. The model takes into account
      the columnar structure of the film, and agrees very well with the experimental
      data.

PMID- 22852331
TI  - Formation mechanism and characterization of black silicon surface by a single
      step wet-chemical process.
AB  - We report a simple single-step etching method for formation of black surface on
      silicon wafer by using HAuCl4-HF-H2O2 etching solution, in which catalytic Au
      particles were deposited in situ. The black surface suppresses the reflectivity
      in a wide spectral region. The formation mechanism involved has been discussed.

PMID- 22852332
TI  - Photocatalytic activity of La, Y Co-doped TiO2 nanoparticles synthesized by
      ultrasonic assisted sol-gel method.
AB  - Bare TiO2 (T), La-doped TiO2 (LT), Y-doped TiO2 (YT), La, Y co-doped TiO2 (LYT)
      were successfully prepared by facile ultrasonic assisted sol-gel synthesis using
      Ti(OC4H9)4 as the precursor. The products were characterized by X-ray diffraction
      (XRD), scanning electron microscope (SEM), UV-visible diffuse reflectance spectra
      (DRS), and X-ray photoelectron spectroscopy (XPS), respectively. The
      photocatalytic activities of anatase samples, with the average particle diameters
      ranging from 14 nm to 21 nm, were evaluated for photodegradation of methyl orange
      (MO). The XPS results indicated that Y atoms were incorporated into titania
      lattice, while La atoms existed on the crystal surface. Due to doping, the
      optical absorption edges of LT, YT, and LYT shifted to the visible light region
      by 21 nm, 29 nm and 35 nm, respectively. The photocatalytic performances of the
      doped samples, such as LT, YT and LYT, were much higher than that of bare TiO2
      under UV-visible light irradiation. And the photoreactivity efficiency of the LYT
      was the highest. It indicated that a strong La-Y synergistic interaction appeared
      to play a decisive role in driving the excellent photocatalytic performance of
      titania.

PMID- 22852333
TI  - Vertical array of ZnO submicrorods on periodically polarity-inverted templates
      using solution method.
AB  - Vertically aligned ZnO nano/submicrorods are grown on periodically polarity
      inverted (PPI) ZnO templates by a solution-based growth method without any
      catalyst. For the selective growth of ZnO submicrorods, PPI ZnO structures are
      used for templates made by using a polarity control technique of ZnO with CrN and
      Cr2O3 intermediate layers. After syntheses of ZnO nanostructures on PPI ZnO, the
      vertically aligned ZnO rods were grown only onto the Zn-polar regions.

PMID- 22852334
TI  - Pt/C doped TiO2/SWNTs as catalyst for methanol oxidation.
AB  - Platinum/carbon doped titanium dioxide/single-walled carbon nanotubes
      (Pt/C/TiO2/SWNTs) were successfully prepared by blending method. These composite
      catalysts were found to exhibit an anatase TiO2 structure with uniform Pt/C and
      the existence of SWNTs can be confirmed by transmission electron microscopy
      (TEM). The composite of Pt/C with TiO2/SWNTs could improve an enhancement in
      catalytic properties upon applying TiO2/SWNTs as catalyst support. The catalytic
      oxidation of methanol of Pt/C doped TiO2/SWNTs is found to be higher as compared
      to the undoped and Pt/C doped materials.

PMID- 22852335
TI  - Characterization and optimized electrochemical performances of LiFe(1-2x)ZrxPO4/C
      nanocomposites as cathode materials for lithium-ion batteries.
AB  - A series of nanocomposite LiFe(1-2x)ZrxPO4/C (x = 0.01,0.02, 0.03, 0.04, 0.06)
      were prepared by carbon thermal reduction method. With this strategy, the Li3PO4
      impurity phase can be obviously reduced in the Zr-doped samples and the
      electrochemical performance is obviously improved by Zr doping compared with the
      undoped one. The best electrochemical performances were observed in
      LiFe(0.92)Zr(0.04)PO4/C as well as good cycle stability.

PMID- 22852336
TI  - Synthesis of Ag@LiFePO4/C composite cathode material by electrodeposition method.
AB  - Ag@LiFePO4/C particles were prepared by a facile and one-step electrodeposition
      method. This core-shell structure cathode material has excellent electrochemical
      performances (both high charge/discharge rates and good cyclability), which can
      meet the demands of many high power applications.

PMID- 22852337
TI  - ZnO nanorod arrays for photoelectrochemical cells.
AB  - The splitting of water using photoelectrochemical (PEC) cells to produce hydrogen
      is one of the most sustainable forms of energy production and more and more 1-D
      nanostructrues semiconductors used as photoelectrodes have been studied
      extensively. However, it is not clear whether the photoconversion efficiencies of
      such nanostructure devices are limited by the architectures of the 1-D
      electrodes. Here, we explore the effect of the architecture like the length and
      width of ZnO nanorods on the PEC cells performance for the first time. The as
      prepared nanorods have diameters of 40-50 nm and lengths of 400-800 nm.
      Preliminary measurements exhibit that the resulting electrodes have promising PEC
      properties. Mott-Schottky measurements give a flat-band potential of +0.10 V, a
      carrier density of 3.7 x 10(17) cm(-3), and a space-charge layer of 26 nm. The
      photocurrent of 800 nm-long nanorods shows 10 times higher than that of 400 nm
      long ones, and an encouraging maximum photoconversion efficiency of 0.25% is
      obtained under illumination of 100 mW/cm2 (AM 1.5), which is among the highest
      reported for an undoped ZnO photoelectrode to date.

PMID- 22852338
TI  - One-pot size and interior-cavity controlled synthesis of ZnO hollow micro-/nano
      structured spheres.
AB  - In this work, ZnO hollow micro-/nano-structured microspheres were prepared via a
      one-pot solution route. The size and interior-cavity of these microspheres could
      be easily controlled by varying the precursor concentration. The hollow spherical
      assemblies were composed of short rod-like building units at low precursor
      concentration. When the precursor concentration increased, one-dimensional (1D)
      "pearl-chain-like" building units formed firstly and then self organized into
      hollow microspheres. The organization process and ripening of "pearl-chain-like"
      building units could be modulated by simply altering the reaction time. When
      tested in photocatalytic experiments, the hollow microspheres composed of loosely
      packed 1D "pearl-chain-like" building units showed higher activity than the
      densely packed ones. This method is very simple, mild, and may provide a new
      strategy to synthesize hierarchical self-assembled hollow structures.

PMID- 22852339
TI  - Improving bioavailability of silybin by inclusion into SBA-15 mesoporous silica
      materials.
AB  - Mesoporous silica SBA-15 (SC) and template occluded SBA-15 (SP) were used to
      increase the bioavailability of silybin, an extremely poorly water soluble drug.
      Silybin was introduced into SC and SP by assembling or self-assembling methods.
      The results of X-ray powder diffraction, differential scanning calorimetry (DSC)
      and N2 adsorption-desorption experiment indicated that amorphous silybin was
      successfully introduced into the mesopores in both SC and SP samples. The
      transmission electron micrograph (TEM) images revealed that the structure of the
      mesoporous materials was not destroyed after the drug loading. Results of
      dissolution rate tests and animal experiments showed that both SC and SP can
      significantly improve the bioavailability of silybin, SP was thus preferred
      because the template needs not to be removed by calcination or extraction.

PMID- 22852340
TI  - Octithiophene on Cu(III) and Au(III): formation and electronic structure of
      molecular chains and films.
AB  - Adsorption and electronic structure of octithiophene (8T) molecules on Cu(III)
      and Au(III) surfaces are investigated using scanning tunneling microscopy (STM)
      and spectroscopy (STS) at room temperature. We find a large difference in
      adsorption behavior of 8T molecules on the two surfaces. At the initial stage of
      adsorption, 8T molecules are stabilized in the form of molecular chain on a
      terrace of Cu(III), whereas neither such chain structure nor isolated 8T
      molecules have been observed on a terrace of Au(III). By increasing the amount of
      adsorbed molecules, a disordered monolayer film is formed on Cu(III) while a well
      ordered monolayer film is formed on Au(III). From the spectroscopic
      investigations using bias-dependent STM images and STS spectra and by comparing
      the data with theoretical calculations, it is found that the electronic property
      of 8T molecules in the molecular chain on Cu(III) is different from that of a
      free-standing 8T molecule while that in the monolayer film on Au(III) keeps
      original character of the free-standing 8T molecule. The present study shows that
      adsorption of 8T molecules on Cu(III) results in a formation of adsorption
      induced states near the Fermi level.

PMID- 22852341
TI  - Multifunctional nanomedicine platforms for cancer therapy.
AB  - Biocompatible nanomaterials have emerged as ideal platforms to develop multi
      functionalization for achieving a compound effect using one system in which each
      component has a specially designed function. In this context, this article
      reviews multifunctional nanomedicine platforms for cancer therapy. The paper
      describes different types of multifunctional nanomedicine platforms, mainly co
      delivery of drugs/genes in a single formulation for synergistic anticancer
      effect, specific strategies for targeting cancer therapy, smart control released
      drug delivery systems responding to certain internal or external stimuli,
      paradigms for theranostics to monitor effects in real time, and combination drug
      with thermal, sound, and light energies mediating multi-mode cancer treatment.
      Multifunctional nanomedicine platforms with different designs and therapeutic
      approaches for cancer and their translation from bench to bedside offer promising
      opportunities to benefit patients in the future.

PMID- 22852342
TI  - Colloidal platinum in hydrogen-rich water exhibits radical-scavenging activity
      and improves blood fluidity.
AB  - The 'colloidal platinum' stabilized with polyvinylpyrrolidone (Pt/PVP-colloid)
      was dispersed in hydrogen-rich water (HW; hydrogen concentration, 0.82 ppm;
      oxidation-reduction potential, -583 mV) or regular water (RW; <0.01 ppm, +218
      mV). And we evaluated the antioxidant activity of Pt/PVP-colloid in HW or RW on
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and improvement of blood
      fluidity under 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced
      oxidative stress. When applied with the 0.25-0.5 ppm Pt/PVP-colloid in RW or HW,
      the level of DPPH radicals decreased to 77.5-59.6% or 16.1-5.6%, in contrast to
      the level as high as 81.3% for HW alone, respectively, as measured by an electron
      spin resonance method. The horse blood, which was subjected to AAPH-induced
      oxidative stress, was incubated for 24 hr with RW or HW, and thereafter required
      13.7 sec (100%) or 5.7 sec (42.3%) for passing through the micro-channels in a
      rheology equipment. When treated with 0.5-1.0 ppm Pt/PVP-colloid in RW or HW, the
      blood passage time in the micro-channels decreased dose-dependently to 9.7-7.3
      sec (71.6-53.8%) or 4.3-1.3 sec (32.8-10.3%), and the rate of micro-channels
      clogged with erythrocyte aggregates decreased to 23.8-21.0% or 15.8-9.8%,
      respectively, from 42.8% for no addition of Pt/PVP. By scanning electron
      microscopy, AAPH-treated erythrocytes lost intact surface morphology on the
      membrane together with protrusions and without hollows, being indicative of
      impaired transforming ability, and the rate of erythrocyte agglutination was
      increased to 46.2%. When treated the horse blood with HW alone significantly
      decreased the rate of erythrocyte agglutination to 29.6%, whereas 1.0 ppm Pt/PVP
      colloid in RW or HW decreased it to 24.1% or 21.1%, respectively. Thus, DPPH
      radical-scavenging and erythrocyte-protecting effects of Pt/PVP-colloid in HW
      were superior to those of Pt/PVP-colloid in RW or Pt/PVP-free HW. The results
      could be mainly attributed to the enhanced antioxidant activity of Pt/PVP in HW,
      which may be due to captured-hydrogen on platinum.

PMID- 22852343
TI  - Shape-dependent photocatalytic activities of bismuth subcarbonate nanostructures.
AB  - Different shaped bismuth subcarbonate ((BiO)2CO3) nanostructures including
      irregular nanoplates, relatively uniform nanoplates and nanocubes were prepared
      and characterized by powder X-ray diffraction (XRD), scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), UV-vis diffuse reflection
      spectroscopy (DRS) and nitrogen adsorption. The photocatalytic performance of the
      as-synthesized (BiO)2CO3 nanostructures on the degradation of Rhodamine B (RhB),
      methyl orange (MO) and methyl blue (MB) were evaluated under UV-vis light
      irradiation (modeling sunlight). The photocatalysis tests showed that all the
      different (BiO)2CO3 nanostructures displayed enhanced photodegradation
      performance compared with commercial (BiO)2CO3. The irregular (BiO)2CO3
      nanoplates exhibited the highest photocatalytic activity on the degradation of
      different organic dyes. (BiO)2CO3 nanosturctures exhibited the different capacity
      to bleach the three organic dyes, which might be attributed to their different
      molecular structures. This work may provide a potential photocatalyst for the
      environmental pollutants treatments.

PMID- 22852344
TI  - Sequencing the miRNAs in maternal plasma from women before and after parturition.
AB  - The goal of the study was to analyze the microRNAs (miRNA) expression that
      differentiates in maternal plasma of women before and after parturition. Here, we
      used high throughput sequencer to analyze the expression change of all microRNAs
      in plasma from pregnant women. Six families of microRNA were also surveyed using
      real-time quantitative PCR. Sequencing result showed that the circulating
      microRNA expression in plasma from pregnant women down regulated remarkably after
      parturition. The quantitative PCR results showed that the differential expression
      of most miRNAs in plasma between before and after parturition was consistent with
      the sequencing result. It is also showed that not only notable differential miRNA
      expression between the plasma from the same woman collected before and after
      parturition, but also between normal plasma and preeclamptic plasma, which
      indicate that miRNAs could be potential biomarker for prenatal diagnosis and
      prognosis. The study suggested circulating miRNAs in plasma of pregnant women
      could be detected more comprehensive by the next generation sequencing
      technology. This research also suggested the differential miRNA expression could
      be related to the existence and clearance of circulating DNA/RNA, which paved a
      new way for studying the origin and path of circulating nucleic acid.

PMID- 22852345
TI  - Light-sensitive liposomes containing coumarin-proteinoid conjugate.
AB  - Photo-sensitive liposomes were prepared by modifying the surface with coumarin
      derivative-proteinoid conjugate. Epoxypropoxy coumarin (EPC) was conjugated to
      proteinoid composed of Asp, Ser and Leu (PASL) using the reaction mixture of
      which EPC/PASL ratio was 8/1 (w/w). The molar ratio of Asp residue/Ser
      residue/Leu residue/EPC residue of the resulting conjugate was calculated to be
      71.1:18.6/6.3/4.0 on 1H NMR spectrum. Egg phosphatidylcholine (egg PC) liposomes
      bearing PASL-EPC conjugate was prepared by hydrating egg PC dry film with a
      buffer solution containing the conjugate. Egg PC/PASL-EPC conjugate ratios (w/w)
      in the preparation were 100:1 to 100:20, and the specific loadings of EPC residue
      in the liposomes were 0.0002 mg/mg to 0.0018 mg/mg. The release from the
      liposomes prepared using the egg PC/PASL-EPC conjugate ratios of 100:5 began to
      markedly increase 30 min after the irradiation of lambda = 254 nm and the release
      degree in 180 min was about 30%. Without the UV irradiation, no appreciable
      release was observed.

PMID- 22852346
TI  - Preparation of anionic polyurethane nanoparticles and blood compatible behaviors.
AB  - The anionic polyurethane nanoparticles (APU-NPs) were obtained by an emulsion
      polymerization method. It was found that the average size of the prepared APU-NPs
      is about 84 nm, and the APU-NPs have zeta-potential of -38.9 mV. The bulk
      characterization of synthesized APU-NPs was investigated by FTIR. The blood
      compatibility of APU-NPs was characterized by in vitro for coagulation tests,
      complement activation, platelet activation, cytotoxicity experiments, and
      hemolysis assay. The results showed that the APU-NPs synthesized in this paper
      are blood compatible with low level of cell cytotoxicity, and the results were
      significant for their potential use in vivo.

PMID- 22852347
TI  - Photoelectrochemical behaviour of uniform growth TiO2 nanotubes via bubble
      blowing synthesised in ethylene glycol with hydrogen peroxide.
AB  - Uniformly sized TiO2 nanotubes with high aspect ratios were synthesised on a
      large substrate (100 mm x 100 mm) via the bubbling system through anodisation of
      Ti in ethylene glycol containing 5 wt% NH4F and 5 wt% H2O2. The benefits of
      bubbling system in producing uniformly sized TiO2 nanotubes throughout the Ti
      foil are illustrated. Moreover, the effects of applied voltage and fluoride
      content on the resulting nanotubes were also considered. Such uniform sized TiO2
      nanotubes are a key to produce hydrogen efficiently using PEC cell. The results
      show higher photocurrent responses for the high aspect ratio, uniform TiO2
      nanotubes because of excellent interfacial electron transfer.

PMID- 22852348
TI  - Effect of low multi-walled carbon nanotubes loading on the crystallization
      behavior of biodegradable poly(butylene adipate).
AB  - The effect of low carboxyl-functionalized multi-walled carbon nanotubes (f
      MWCNTs) loading on the crystallization behavior of biodegradable poly(butylene
      adipate) (PBA) was studied with various techniques in this work. For the
      nonisothermal melt crystallization, f-MWCNTs accelerate the crystallization
      process of PBA apparently due to the heterogeneous nucleation effect. The Ozawa
      method fails to describe the nonisothermal crystallization process of neat PBA
      and its nanocomposite. Isothermal melt crystallization kinetics of neat PBA and
      its nanocomposite was analyzed by the Avrami equation. The overall isothermal
      crystallization rate of neat PBA and its nanocomposite increases with increasing
      crystallization temperature. The addition of f-MWCNTs accelerates the isothermal
      crystallization of PBA as compared with that of neat PBA at a given
      crystallization temperature, indicative of the nucleating agent effect of f
      MWCNTs; however, the crystallization mechanism does not change. The crystal
      structure of PBA remains unchanged in the PBA/f-MWCNTs nanocomposite despite the
      presence of f-MWCNTs.

PMID- 22852349
TI  - From ZnO hollow microspheres to radical nanorod arrays.
AB  - Nanstructured ZnO has exhibited attractive multifunction for various
      applications, however, the nanostructures are so sensitive to the fabrication
      conditions that it is not easy to control the produced morphology. In this paper,
      ZnO hollow microspheres and radical nanorod arrays were fabricated based on the
      controllable solution chemical reaction. The growth process was adjusted through
      the concentration of sodium alginate and ammonia, which provided a molecular
      template as nucleation sites and basic reaction microenvironment, respectively.
      The growth mechanism was proposed by analyzing the action of the sodium alginate
      and ammonia. The morphology evolution was supported by the serial observation
      through scanning electronic microscopy and high-resolution transmission
      electronic microscopy.

PMID- 22852350
TI  - The application of nanoemulsions with different orange oil concentrations to
      remediate crude oil-contaminated soil.
AB  - The petroleum industry stands out for causing significant environmental risks
      from contamination of the air, water and soil. The removal of organic pollutants
      from the environment poses a great technological challenge, making it
      increasingly necessary to develop efficient clean-up technologies. Surfactant
      solutions have been used to remediate soils and aquifers contaminated by
      hydrocarbons or crude oil derivatives. The aim of this study was to develop
      nanoemulsions and analyze their efficiency in extracting crude oil from a sand
      sample. The nanoemulsions were prepared by the phase inversion temperature (PIT)
      method. The oil phase consisted of orange oil and the nonionic surfactant
      ethoxylated lauryl ether (Ultrol L70) was used to stabilize the nanoemulsions.
      The surfactant concentrations were varied from 10 to 12 wt% and the oil phase
      from 5 to 20 wt%. The efficiency of extraction of oil from sand was assessed
      using the two nanoemulsions that presented the greatest stability (containing 5
      wt% oil phase with 12 wt% surfactant and 20 wt% oil phase with 10 wt%
      surfactant). A 2(3) factorial experimental design with center point was used to
      evaluate and improve the soil washing process, varying the time, temperature and
      agitation speed of the system. The highest efficiencies were obtained at 45
      degrees C.

PMID- 22852351
TI  - Nonionic Brij surfactant-mediated synthesis of raspberry-like gold nanoparticles
      with high surface area.
AB  - We report a rapid, simple, single-step, and high-yielding solution-phase
      synthesis of raspberry-like gold nanoparticles (Au RLNPs) with rich edges and
      high surface areas. Au RLNPs were synthesized through the reduction of HAuCl4
      simply mediated by nonionic Brij surfactant in basic conditions without any other
      reducing agents or organic molecules. The synthesized nanoparticles possessed
      high surface areas and were stable in basic or neutral conditions, which are
      potentially useful structural factors for the applications. The unique, highly
      red-shifted surface plasmon resonances (SPRs) of Au RLNPS originate from their
      rough, raspberry-like surfaces. The sizes of Au RLNPs were controllable by
      varying the amounts of NaOH and HAuCl4. However, there are very few reported
      facile syntheses of size-controlled multi-branched gold nanoparticles simply
      mediated by surfactant without any other reducing agents or organic molecules.

PMID- 22852352
TI  - Monitoring the mechanical behaviour of electrically conductive polymer
      nanocomposites under ramp and creep conditions.
AB  - Various amounts of carbon black (CB) and carbon nanofibres (CNF) were dispersed
      in an epoxy resin to prepare nanocomposites whose mechanical behaviour, under
      ramp and creep conditions, was monitored by electrical measurements. The
      electrical resistivity of the epoxy resin was dramatically reduced by both
      nanofillers after the percolation threshold (1 wt% for CB and 0.5 wt% for CNF),
      reaching values in the range of 10(3)-10(4) omega . cm for filler loadings higher
      than 2 wt%. Due to the synergistic effects between the nanofillers, an epoxy
      system containing a total nanofiller amount of 2 wt%, with a relative CB/CNF
      ratio of 90/10 was selected for the specific applications. A direct correlation
      between the tensile strain and the increase of the electrical resistance was
      observed over the whole experimental range, and also the final failure of the
      samples was clearly detected. Creep tests confirmed the possibility to monitor
      the various deformational stages under constant loads, with a strong dependency
      from the temperature and the applied stress. The obtained results are encouraging
      for a possible application of nanomodified epoxy resin as a matrix for the
      preparation of structural composites with sensing (i.e., damage-monitoring)
      capabilities.

PMID- 22852353
TI  - Morphology control of self-catalyzed germanium nanostructures with graphitic
      carbon shell.
AB  - The crystalline germanium nanowires (GeNWs) with a uniform graphitic carbon shell
      were prepared via a conventional low-pressure chemical vapor deposition method
      without any external catalyst. The GeNWs grown at low temperature (Tg < 500
      degrees C) have a uniform diameter with a large expect ratio of more than 10(3).
      With increasing the growth temperature (Tg > 500 degrees C), however, the
      nanowire morphology is dramatically changed into a hybrid structure where highly
      dense Ge nanoparticles (GeNPs) with a diameter of 5-10 nm are attached onto the
      Ge nanowires. The nanostructures consist of crystalline Ge-core and very thin
      graphitic carbon shell. The possible mechanism of anisotropic growth and the
      control of morphological transition from uniform nanowires to NW/NP hybrid
      structures are discussed and demonstrated.

PMID- 22852354
TI  - The detection of p53 gene via fluorescence quenching of quantum dot in
      microfluidic chip.
AB  - Recently, quantum dot (QD) has been used widely in the field of bio assay
      including cell imaging, biomarker, and fluorescence resonance energy transfer
      (FRET) sensor. The DNA assay without labeling process has several advantages
      including low cost, short time, and simplicity. Microbeads of agarose, glass, and
      polystyrene have been used as a solid support in microfluidic devices to trace
      molecules. The main advantages of microfluidics include high throughput, short
      analysis time, small sample volume, and high sensitivity. PDMS based microfluidic
      chips were prepared for the detection of p53 gene by using QD-DNA conjugate. The
      microfluidic chip has a weir in the channel to trap microbeads to which QD-DNA
      probes bind. Carboxylated CdSe/ZnS QDs (wavelength of emission: 605 nm) could
      bind to microbeads of polystyrene/divinyl benzene via EDC/NHS crosslinking
      reaction. The target gene and DNA intercalating dye (TOTO-3) were loaded into the
      micro-channel. Fluorescence quenching from QDs by intercalating dye was observed
      after hybridization of DNA at the weir in the channel of microfluidic chip. The
      fluorescence quenching from QDs by TOTO-3 was dependent on the concentration of
      target gene. This experiment shows the possibility of rapid detection of DNA via
      bead-QD complex on microfluidic chip.

PMID- 22852355
TI  - Cell chip based monitoring of toxic effects on dopaminergic cell.
AB  - Oxidative stress has been implicated in pesticide-induced neurotoxicity, base on
      its role in cascade of biochemical changes that lead to dopaminergic neuronal
      cell death. The present study examined the role of oxidative stress and the
      electrochemical detection by polychlorinated biphenyls (PCBs)-induced toxicant in
      SH-SY5Y cell. The cells were seed in the RED (Arg-Gly-Asp) nanopatterned coating
      gold substrate and treated with different concentration of PCBs for 24 h in
      culture, which induced the change of the cyclic voltammetry (CV) current peak.
      The CV results showed that PCB significantly decreased the current peaks in dose
      and time-dependent manner. After antioxidant treatment, the CV of the PCB-treated
      cell chip increased the current peak. Especially, gluthaione and catalase prevent
      PCB-induced decrease of CV current peak in the cell. The results demonstrated
      that the current peak decreased by the PCB and recovered by the antioxidant
      enzyme. In conclusion, results suggest that the electrochemical-based chip
      provide crucial information to improvement toward a cell chip system for drug
      screening application.

PMID- 22852356
TI  - Nanoscale biofilm modification-method concerning a myoglobin/11-MUA bilayers for
      bioelectronic device.
AB  - We developed surface modification tools for the fabrication of a bioelectronic
      device which consists of a myoglobin monolayer self-assembled on an 11-MUA layer.
      To utilize a single protein as the active element, it was necessary to reduce
      protein aggregation on the protein layer in the nanobio electronic device, which
      was developed in our previous study and shown to display basic biomemory
      functions. Here, the reduction of myoglobin aggregation was accomplished by using
      3-(3-cholamidopropyl) dimethylammonio-11-propanesulfonate (CHAPS) to fabricate a
      well-defined protein layer on the bioelectronic device. We investigated two
      different surface modification methods for making well oriented biofilm. The
      effects of CHAPS on the formation of a myoglobin layer self-assembled on an 11
      MUA layer were examined by atomic force microscopy and Raman spectroscopy. The
      size of the myoglobin aggregates was reduced from 200-250 nm to 10-40 nm
      depending on treatment method. The sustaining redox property of the CHAPS treated
      myoglobin layer was examined using cyclic voltammetry. Using these techniques, we
      found that after surfactant CHAPS treatment, protein aggregation was dramatically
      reduced and the protein layer still maintained its inherent electrochemical
      properties.

PMID- 22852357
TI  - TiO2-grafted multi-walled carbon nanotubes for dye-sensitized solar cells.
AB  - Dye-Sensitized Solar Cells (DSSCs) comprised of TiO2 porous films with multi
      walled carbon nanotubes (MWNT) were prepared at low temperature (150 degrees C).
      MWNT were incorporated to facilitate the fast electron transport resulting from
      metallic properties of carbon nanotubes. In order to enhance the effect of MWNT
      incorporation, TiO2-grafted MWNT (TiO2-MWNT) was synthesized which can increase
      the electron transport rate further due to proximity of TiO2 to MWNT The presence
      of TiO2 nanoparticles on the surface of MWNT was confirmed by electron microscopy
      and energy dispersive X-ray spectroscopy. As in the DSSCs prepared through high
      temperature sintering of photoanodes, the maximum content of MWNT incorporated
      into TiO2 was limited to 0.01 wt% relative to TiO2. TiO2 photoanodes including
      TiO2-grafted MWNT (TiO2-MWNT/P25) enhanced the cell efficiencies by ca. 28% and
      14%, relative to TiO2 photoanodes without and with MWNT respectively, reaching
      the efficiency of 5.0%. Electrochemical impedance spectroscopy (EIS) was utilized
      to examine the effect of incorporation of TiO2 nanoparticles grafted to MWNT on
      the cell performance.

PMID- 22852358
TI  - Synthesis of fluorene-based semiconducting copolymers for organic solar cells.
AB  - Semiconducting polymers composed of 2,2'-(9,9-dioctyl-9H-fluorene-2,7
      diyl)dithiophenes (F8T2s) and (2E,2'E)-3,3'-(2,5-bis(octyloxy)-1,4-phenylene)
      bis(2-(5-bromothiophene-2-yl)acrylonitrile)s (OPTANs) have been synthesized
      through Pd(O)-catalyzed Suzuki coupling polymerization by controlling the monomer
      ratio. The synthesized polymers were confirmed to exhibit good solubility in
      common solvents, simple processability, and thermal stability up to 350 degrees
      C. The highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular
      orbitals (LUMOs), and optical band-gap energies were determined using cyclic
      voltammetry (CV) and UV-visible spectrometry. The synthesized polymers showed
      their maximum absorption and edge at around 520 and 650 nm, respectively. The
      optical band-gap energies of the polymers were determined to be 1.89 eV. Bulk
      heterojunction organic solar cells were fabricated using the conjugated polymer
      as the electron donor, and 6,6-phenyl C61-butyric acid methylester (PC61BM) or
      6,6-phenyl C71-butyric acid methylester (PC71BM) as the electron acceptor. The
      power conversion efficiencies (PCEs) of the solar cells based on polymer:PC71BM
      (1:1) and polymer:PC71BM (1:2) were 0.68% and 1.22%, respectively, under air mass
      1.5 global (AM 1.5 G) illumination at 100 mW/cm2.

PMID- 22852359
TI  - Synthesis and characterization of polystyrene brushes for organic thin film
      transistors.
AB  - We synthesized and characterized polystyrene brushes on a silicon wafer using
      surface-initiated atom transfer radical polymerization. The thickness of the
      polymer brush was controlled by adjusting the reaction time. We investigated
      monomer conversion as well as the molecular weight and density of the polymer
      brushes. When the monomer conversion reached 100%, the number-average molecular
      weight and film thickness reached 135,000 and 113 nm, respectively. The estimated
      densities of the synthesized polystyrene brushes were in the range 0.34-0.54
      chains/nm2, high enough to be categorized in the "concentrated brush" regime. The
      synthesized polymer brush was used as an insulating layer in an organic thin-film
      transistor. Organic thin-film transistors were fabricated using pentacene as an
      active p-type organic semiconductor and a polystyrene brush on a SiO2 layer as a
      gate dielectric. The pentacene based organic thin-film transistor with the
      polystyrene brush exhibited a field-effect mobility microFET of 0.099 cm2/(V x
      s).

PMID- 22852360
TI  - The effect of the molecular structure on the optoelectronic properties of a
      fluorophore for use in organic light-emitting diodes.
AB  - A novel yellow light-emitting material, (2Z)-3-[4,4"-bis(dimethylamino)
      1,1':4',1"-terphenyl-2'-yl]-2-phenylacrylonitrile (BDAT-P), having the modified
      molecular structure from red fluorescent compound, (2Z, 2'Z)-3,3'-[4,4"
      bis(dimethylamino)-1,1':4',1"-terphenyl-2',5'-diyl]bis(2-phenylacry-lonitrile)
      (ABCV-P), was synthesized in order to study the effect of the molecular structure
      on the optoelectronic properties of a light-emitting material. UV-visible
      absorption and photoluminescence (PL) emission peaks measured in various solvent
      systems were summarized in Table I. In the respective solvent system, the
      bathochromic shift of PL emission peak relative to the peak of UV-visible
      absorption was much larger for ABCV-P with two electron donor-acceptor pairs than
      for BDAT-P with one electron donor-acceptor pair. EL emission peaks of devices
      using BDAT-P and ABCV-P as the host emitters measured to be 573 and 613 nm,
      respectively. Commission Internationale de l'Eclairage (CIExy) coordinate of
      device using BDAT-P was measured to be (0.4855, 0.5021) at 7 V, which was
      correspond to the yellow color.

PMID- 22852361
TI  - Improvement of photovoltaic properties by addition of a perylene compound in
      P3HT:PCBM BHJ system.
AB  - The synthesized n-type perylene derivative, N,N'-bis-(4-bromophenyl)-1,6,7,12
      tetrakis(4-n-butoxy-phenoxy)-3,4,9,10-perylene tetracarboxdiimide (PIBr), was
      applied as an additive to polymer solar cells (PSCs) with P3HT [poly(3
      hexylthiophene)]:PCBM [[6,6]-phenyl C61-butyric acid methyl ester] blend films.
      Without post thermal annealing, a considerable improvement of about 98% in power
      conversion efficiency was achieved by the addition of 1 wt% PIBr into a P3HT:PCBM
      layer, when compared with that of reference cell without the additive. The
      results, in combination with relevant data from UV-Vis. absorption,
      photoluminescence, X-ray measurements and carrier mobility studies, revealed that
      the addition of the perylene compound within active layer contributed to more
      effective charge transfer and enhanced electron mobility.

PMID- 22852362
TI  - Efficient triplet exciton confinement of blue- and white-organic light emitting
      diodes using a new host material.
AB  - We have demonstrated lower driving voltage and efficient blue phosphorescent
      organic light emitting diodes (PHOLEDs) using iridium(III) bis[(4,6-di
      fluoropheny)-pyridinato-N,C2] picolinate (Flrpic) doped in new host material 9-(4
      (triphenylsilyl)phenyl)-9H-carbazole (SPC) and 2,2',2"-(1,3,5-benzenetryl)tris(1
      phenyl)-1H-benzimidazol (TPBi) as double-emitting layer (D-EML) system. The D-EML
      was employed to have good electron transportability and exciton confinement.
      Additionally, we fabricated white organic light-emitting diode (WOLED) using a
      phosphorescent red emitter; bis(2-phenylquinolinato)-acetylacetonate iridium III
      (Ir(pq)2acac) doped in SPC and TPBi as D-EML. The properties of white device
      exhibited a maximum luminous efficiency of 19.03 cd/A, a maximum external quantum
      efficiency of 9.91%, and a maximum power efficiency of 12.30 lm/W. It also showed
      white emission with CIE(x,y) coordinates of (x = 0.38, y = 0.37) at 8 V.

PMID- 22852363
TI  - Fabrication of human IgG sensors based on porous silicon interferometer
      containing Bragg structures.
AB  - A simply modified biosensor based on protein A-modified distributed Bragg
      reflectors (DBR) porous silicon (PSi) chip for the detection of human
      immunoglobin G (IgG) are developed. The fabrication, optical characterization,
      and surface derivatization of DBR PSi are investigated. The sensor system studied
      consist of multi-layer of porous silicon modified with protein-A. The sensor is
      operated by the measurement of the reflection peak in the white light reflection
      spectrum. Molecular binding is detected as a shift in wavelength of reflection
      peaks.

PMID- 22852364
TI  - Improved electrical and optical properties of ITO/Ag/ITO films by using electron
      beam irradiation and their application to ultraviolet light-emitting diode as
      highly transparent p-type electrodes.
AB  - We have investigated the effect of insertion of a Ag layer in ITO film as well as
      electron beam irradiation to the multilayer films on the electrical and optical
      properties of the ITO-based multilayer deposited by magnetron sputtering method
      at room temperature. Inserting a very thin Ag layer between ITO layers resulted
      in a significant decrease in sheet resistance and increased the optical band gap
      of the ITO/Ag/ITO multilayer to 4.35 eV, followed by a high transparency of
      approximately 80% at a wavelength of 375 nm. We have also fabricated ultraviolet
      light-emitting diodes (LED) by using the ITO/Ag/ITO p-type electrode with/without
      electron beam irradiation. The results show that the UV-LEDs having ITO/Ag/ITO p
      electrode with electron beam irradiation produced 19% higher optical output power
      due to the low absorption of light in the p-type electrode.

PMID- 22852365
TI  - In situ polymerization of acetylene polymer on single-walled carbon nanotube and
      its application to photoinduced charge transfer system.
AB  - An acetylene polymer is formed on single-walled carbon nanotubes (SWNTs) using in
      situ polymerization. The acetylene polymers/SWNTs composite is hydrophilic even
      water-soluble, and has a structure of donor/acceptor dyad. In measurements of
      photocurrents-voltage curves, the composite film exhibits a power conversion
      efficiency of 1.50 x 10(-2%) under illumination (I = 80 mW/cm2, air mass 1.5
      condition).

PMID- 22852366
TI  - Synthesis and structural-optical properties of Ga-doped ZnO nanowires by hot
      walled pulsed laser deposition method.
AB  - Well-aligned single-crystalline zinc oxide (ZnO) and Ga doped ZnO (GZO) NWs (NWs)
      were successfully fabricated on Au film catalyzed sapphire substrate using vapor
      liquid-solid (VLS) method in hot-walled pulsed laser deposition (HW-PLD). The
      structural and optical properties of Ga doped ZnO NWs have been investigated
      depending on various concentration of Ga dopants in ZnO NWs. As increasing Ga
      concentration, stacking faults were observed by using FE-SEM and an exciton bound
      to a neutral donor (D(0)X) peak was clearly observed by using PL spectra. From
      the structural and optical properties, the ZnO NWs by doping could be application
      to electronic and optoelectronic devices, such as nano-FETs, nano-inverters, nano
      logic circuits and nano-sensors.

PMID- 22852367
TI  - Failure analysis of InGaN/GaN high power light-emitting diodes fabricated with
      ITO transparent p-type electrode during accelerated electro-thermal stress.
AB  - We have investigated the high-temperature degradation of optical power as well as
      electrical properties of InGaN/GaN light-emitting diodes (LEDs) fabricated with
      ITO transparent p-electrode during accelerated electro-thermal stress. As the
      thermal stress increased from 150 degrees C to 250 degrees C at a electrical
      stress of 200 mA, the optical power of the LEDs was significantly reduced.
      Degradation of the optical power was thermally activated, with the activation of
      0.9 eV. In addition, the activation energy of the degradation of optical power
      was fairly similar to that of the degradation of series resistance of the LEDs,
      1.0 eV, which implies that the increase in the series resistance may result in
      the severe degradation of optical power. We also showed that the increase in the
      series resistance of the LEDs during the accelerated electro-thermal stress can
      be attributed to reduction of the active acceptor concentration in the p-type
      semiconductor layers and local joule heating due to the current crowding.

PMID- 22852368
TI  - Preparation and characterization of MgO nanorods coated with SnO2.
AB  - MgO nanorods have been grown by thermal evaporation of Mg3N2 powders on Si (100)
      substrates coated with gold (Au) thin films. The MgO nanorods grown on Al2O3
      (0001) were 0.1-0.2 microm in diameter and up to a few tens of micrometers in
      length. MgO/SnO2 coaxial nanorods have also been prepared by atomic layer
      deposition (ALD) of SnO2 onto the nanorods. Transmission electron microscopy
      (TEM) and X-ray diffraction (XRD) analysis results indicate that the MgO-cores
      and the SnO2 shells of the annealed coaxial nanorods are of a single crystalline
      nature with cubic and orthorhombic structures, respectively. The
      photoluminescence (PL) spectroscopy analysis results show that SnO2 coating
      slightly increases the PL emission intensity of MgO nanorods. The PL emission of
      the SnO2-coated MgO nanorods is found to be considerably enhanced by thermal
      annealing and to strongly depend on the annealing atmosphere. The PL emission
      intensity of the MgO/SnO2 coaxial nanorods has been significantly increased by
      annealing in a reducing atmosphere. The origin of the PL enhancement by annealing
      in a reducing atmosphere is discussed on the basis of energy-dispersive X-ray
      spectroscopy analyses.

PMID- 22852369
TI  - Preparation of gradient polyacrylate brushes in microchannels.
AB  - Gradient poly(2-hydroxyethyl methacrylate) brushes were synthesized by surface
      initiated atom transfer radical polymerization (ATRP) confined within a
      microfluidic system on a silicon wafer. For ATRP, surface initiator, 11-((2
      bromo, 2-methyl) propionyloxy) undecyltrichlorosilane (BUC), was synthesized, and
      allowed to self-assemble in a monolayer on the Si wafer, as analyzed by XPS to
      confirm the presence of an ester group of BUC. A solution containing 2
      hydroxyethylmethacrylate, Cu catalyst, and bipyridin was allowed to flow in a
      microchannel and polymerize, resulting in the brushes with a gradient of
      thickness on the Si wafer. Using ellipsometry and ATR-IR, we verified the
      gradients of well established brushes on the Si wafer. AFM and contact angle data
      showed that wettability of the brushes did not exhibit a linear relationship with
      hydrophilicity.

PMID- 22852370
TI  - Red phosphorescent organic light-emitting diodes based on the simple structure.
AB  - We demonstrated that the simple layered red phosphorescent organic light-emitting
      diodes (OLEDs) are possible to have high efficiency, low driving voltage, stable
      roll-off efficiency, and pure emission color without hole injection and transport
      layers. We fabricated the OLEDs with a structure of ITO/CBP doped with
      Ir(pq)2(acac)/BPhen/Liq/Al, where the doping concentration of red dopant,
      Ir(pq)2(acac), was varied from 4% to 20%. As a result, the quantum efficiencies
      of 13.4, 11.2, 16.7, 10.8 and 9.8% were observed in devices with doping
      concentrations of 4, 8, 12, 16 and 20%, respectively. Despite of absence of the
      hole injection and transport layers, these efficiencies are superior to
      efficiencies of device with hole transporting layer due to direct hole injection
      from anode to dopant in emission layer.

PMID- 22852371
TI  - Synthesis and photovoltaic properties of a new thiophene-cyclopentadiene-based
      conjugated polymer.
AB  - A new low-band gap polymer containing thiophene and cyclopentadiene, poly(5,2,2'
      dioctyldithio-phenylcyclopentadiene) (PDTCP), has been synthesized via the FeCl3
      oxidative polymerization. PDTCP showed a broad absorption band and a low energy
      band gap of 1.82 eV. The photoluminescence (PL) of PDTCP is completely quenched
      upon addition of PCBM indicative of efficient charge transfer. Bulk
      heterojunction organic photovoltaic cells (OPVs) fabricated from PDTCP as an
      electron donor showed an open-circuit voltage (V(OC)) of 0.50 V, a short-circuit
      current (J(SC)) of 1.24 mA/cm2, and the power conversion efficiency of up to
      0.20% under AM 1.5 (100 mW/cm2).

PMID- 22852372
TI  - Detection of nitroaromatic compounds based on phenylethylene-derivatized porous
      silicon.
AB  - Nanocrystalline porous silicon (PSi) surfaces have been used to detect
      nitroaromatic compounds in vapor phase. The mode of photoluminescence (PL) is
      emphasized as a sensing attitude or detection technique. Quenching of PL from
      nanocrystalline porous surfaces as a transduction mode is measured upon the
      exposure of nitroaromatic compounds. To verify the detection of explosives, the
      surface of PSi is functionalized with different groups. The quenching mechanism
      of PL is attributed to the electron transfer behaviors of quantum-sized nano
      crystallites in the PSi matrix to the analytes (nitroaromatics). An attempt has
      been done to prove that the surface-derivatized photoluminescent PSi surfaces can
      act as versatile substrates for sensing behaviors due to having a large surface
      area and highly sensitive transduction mode.

PMID- 22852373
TI  - Trimethylsilane-containing donor-acceptor-donor type material for red fluorescent
      organic light-emitting diodes.
AB  - In this paper, we described a donor-acceptor-donor type red fluorescence
      material, which have the bulky trimethylsilane groups in the donor moieties. To
      explore the electroluminescence properties of these materials, multilayered OLEDs
      were fabricated with a device structure of ITO/2-TNATA (60 nm)/NPB (40 nm)/Red 1
      (2%):rubrene (50%):Alq3 (30 nm)/Alq3 (60 nm)/Liq (3 nm)/Al (100 nm). A device
      using Red 1 as the dopant material showed a maximum luminance of 5138 cd/m2 at
      12.0 V, maximum luminous efficiencies of 1.62 cd/A, and maximum power
      efficiencies of 1.04 lm/W. The Commission Internationale de L'Eclairage
      coordinates of this device was (0.67, 0.33) at 7.0 V, which indicated stable
      color chromaticity at various voltages.

PMID- 22852374
TI  - Transparent nanocomposites of high refractive index based on epoxy resin and TiO2
      nanoparticle.
AB  - A stepwise sol-gel method for the synthesis of stable colloidal TiO2 using
      hydrolysis and condensation reactions of titanium tetraisopropoxide (TTP) was
      investigated. The surface modification was carried out using 3
      glycidoxypropyltrimethoxysilane (GPTMS). The particle size range of the modified
      TiO2 observed by TEM was 3-8 nm. The nanocomposites based on an epoxy resin and
      the modified TiO2 showed strong UV absorption, but maintained high transmittance
      within the visible region. TEM images of the nanocomposites confirmed the
      homogenous and fine dispersion of the TiO2 nanoparticles in the epoxy resin. The
      refractive index of the nanocomposites increased linearly with increasing TiO2
      content. With 60% TiO2 by weight, the transmittance and refractive index of the
      nanocomposite were 98.4% and 1.657, respectively.

PMID- 22852375
TI  - Sensitivity-tuned CO gas sensors with tailored Ga-doping in ZnO nanowires.
AB  - Sensitivity-customization of zinc oxide (ZnO) nanowire (NW) gas sensors has been
      demonstrated by controlling Ga-doping, thereby tuning the resistance of the NWs.
      Both un-doped and 5 weight% Ga-doped ZnO (GZO) NWs are synthesized for the highly
      sensitive sensing within a narrow detection window and a less sensitive one
      within an expanded window, respectively. We have employed hot-walled pulsed laser
      deposition (HW-PLD) for the NW synthesis. With CO gas injection, the resistance
      reduction of NWs is detected and analyzed in a self-designed gas chamber that
      guarantees the precise control of gas flow and, gas concentration, as well as
      temperature. NW sensitivity is proportional to the sensing temperature and
      inversely proportional to the doping concentration resulting in widening the
      sensing window up to 230 times by the 5 wt.% Ga-doping.

PMID- 22852376
TI  - White organic light-emitting diodes for emotion solid-state lighting.
AB  - The authors have demonstrated white organic light-emitting diodes for emotion
      solid-state lighting (ESSL) by using hole modulating layer (HML), N,N'-diphenyl
      N,N'-bis-[4-(phenyl-m-tolyl-amino)-phenyl]-biphenyl-4,4'-diamine and N,N'-bis-(1
      naphyl)-N,N'-diphenyl-1,1'-biphenyl-4, 4'-diamine, and mixed spacer (MS), 4,4',4"
      tris(N-carbazolyl)-triphenylamine and {9,9-dimethyl-7-[10-(naphthalen-2
      yl)anthracen-9-yl]-9H-fluoren-2-yl}triphenylsilane, respectively. The HML and MS
      were used for unbalance of holes and electrons. The ESSL showed various white
      light chromaticities of Commission Internationale de l'Eclairage coordinates from
      (0.46,0.42) as warm white emission to (0.29, 0.36) as cold white emission.

PMID- 22852377
TI  - Thermally stable carbazole-diimides as hole transport materials for organic light
      emitting devices.
AB  - We synthesized new carbazole-diimide hole-transporting materials with different
      dianhydride groups by thermal imidization. The imide moieties were introduced to
      improve thermal stability of a carbazole hole transport molecule. Result showed
      that the carbazole-diimdes exhibit good thermal stability with glass transition
      temperature of 142-182 degrees C and degradation temperature of approximately 450
      degrees C as well as good optical transparency in the visible region. The organic
      light-emitting device (OLED) using alicyclic diimide (CBCZ) shows maximum
      luminance approximately 8,600 cd/m2 at 12 V and current efficiency of 2.1 cd/A.
      With optimization of fabricating conditions, the thermally stable CBCZ is
      expected to be used as a promising hole-transporting material with higher
      efficiency and durability.

PMID- 22852378
TI  - Effect of number and length of outerwalls on cantilevered-carbon-nanotube
      resonators.
AB  - In this paper, we investigated the resonant frequencies of multi-walled carbon
      nanotube (MWCNT) resonators with short outertubes according to the classical
      molecular dynamics approach. The resonant frequencies of the MWCNT resonators
      with short outertubes were influenced in both the wall number and the length of
      the short outertubes. The resonance frequencies of MWCNTs with short outertubes
      could be modeled by Gaussian distribution functions. Both the bandwidth and the
      sensitivity increased with increasing the wall number of the outertubes. The
      maximum frequency increased with increasing the diameter and with increasing the
      wall number of the outertubes for MWCNTs. So the effects of increasing the wall
      number of the outertubes were very important factors for understanding the
      vibrational frequency changes of MWCNTs with short outertubes as well as the
      effect of increasing the lengths of the outertubes.

PMID- 22852379
TI  - Novel photoactive fluorene-based terpolymers incorporating carbazole for
      photovoltaic application.
AB  - A series of novel photoactive conjugated terpolymers based on N-alkyl carbazole,
      9,9-didecylfluorene, and bis(thienyl)benzothiadiazole were synthesized by the Pd
      catalyzed Suzuki polymerization method with various molar ratios of the carbazole
      derivatives. Electron-deficient benzothiadiazole and electron-rich carbazole
      moieties were incorporated into the polymer backbone to obtain the broad
      absorption spectrum and to improve the hole-transporting characteristics,
      respectively. The polymer solar cell (PSC) was fabricated with a layered
      structure of ITO/PEDOT: PSS/polymer:C71-PCBM (1:3)/LiF/Al. The best performance
      of PSC was obtained at P1:C71-PCBM whose reaches a power conversion efficiency
      (PCE) of 2.62%, with a short circuit current density (J(SC)) of 8.61 mA/cm2, an
      open circuit voltage (V(OC)) of 0.82 V, and a fill factor (FF) of 0.37 under AM
      1.5 G irradiation (100 mW/cm2).

PMID- 22852380
TI  - Efficient inverted bulk heterojunction photovoltaic devices using a transparent
      polymeric interfacial buffer layer with C60 pendant and UV curable groups.
AB  - We demonstrate the synthesis of a transparent, polymeric n-type material (M1)
      consisting of C60 pendant and UV curable groups in side chains. This material
      (M1) is employed as a polymeric n-type interfacial buffer layer for an efficient
      inverted bulk heterojunction (BHJ) photovoltaic device based on regioregular
      poly(3-hexylthiophene):[6,6]-phenyl C61 butyric acid methyl ester (P3HT:PC61BM)
      active layer. Under simulated solar illumination of AM 1.5G (100 mW/cm2), the
      highest efficient devices fabricated with a configuration of ITO/interfacial
      buffer layer (M1,10 nm)/P3HT:PC61BM (1:0.9 w:w) (120 nm)/PEDOT:PSS (30 nm)/Ag
      (100 nm) achieve an average power conversion efficiency PCE of 2.16%, with short
      circuit current J(SC) = 6.70 mA/cm2, fill factor FF = 54.2%, and open-circuit
      voltage V(OC) = 0.60 V. This result is comparable to the inverted BHJ
      photovoltaic devices fabricated with Cs2CO3, one of widely used as a buffer
      layer. The synthesized M1 have thus proven to be promising polymeric interfacial
      buffer layer for high efficient BHJ photovoltaic devices.

PMID- 22852381
TI  - Effects of the surface treatment with monolayers of twisted biaryls on the
      efficiency of pentacene thin-film transistors.
AB  - A pentacene thin-film transistor (TFT) was fabricated on a SiO2 gate insulator
      modified with twisted biaryls. The biaryl monolayer, in particular a binaphthyl
      (BN) monolayer, is amorphous surface where the naphthalene rings are randomly
      oriented with no lateral order because of their rigid, twisted, and asymmetric
      shape. When the BN monolayer was used for the surface treatment of SiO2, large
      grains were obtained in the early stages of the pentacene crystal growth. The
      pentacene TFT had a field effect mobility (microm) in excess of 0.4 cm2/Vs and an
      on/off ratio greater than 10(5). The surface treatment improved the mobility of
      the pentacene TFT by a factor of 50% compared with non-treated devices. The
      morphology of the semiconductor layer was investigated using atomic force
      microscopy (AFM) and X-ray diffraction (XRD).

PMID- 22852382
TI  - Synthesis and photovoltaic properties of new conjugated polymers based on
      benzo[1,2-b:4,5-b']dithiophene.
AB  - New conjugated polymers based on benzo[1,2-b:4,5-b']dithiophene, poly(benzo[1,2
      b:4,5-b'] dithiophene-alt-bithiophene) (PBT-2T) and poly(benzo[1,2-b:4,5
      b']dithiophene-alt-terthiophene) (PBT-3T), have been synthesized via the Stille
      coupling reaction and their optical and electrochemical properties were
      characterized by UV-vis, photoluminescence (PL) and cyclic voltammetry (CV)
      measurements. Compared to PBT-2T, PBT-3T film showed clearly red-shifted UV
      visible absorption and PL spectra with maxima at 511 and 653 nm, respectively.
      Especially, PBT-3T containing terthiophene showed very small optical band gap of
      1.65 eV. The PBT-2T and PBT-3T showed the power conversion efficiencies of 0.25%
      and 0.34%, respectively, under AM 1.5 (100 m/cm2).

PMID- 22852383
TI  - Orange-red phosphorescent OLEDs using iridium(III) complexes with
      benzoylphenylpyridine ligands containing fluorine and trifluoromethyl groups.
AB  - We have designed and synthesized four orange-red phosphorescent Ir(III) complexes
      based on the benzoylphenylpyridine ligand with fluorine and trifluoromethyl
      substitution. Multilayered OLEDs were fabricated using these complexes as dopant
      materials. Particularly, by using 1 as a dopant in the emitting layer, a highly
      efficient orange-red OLED was fabricated, showing a maximum luminance of 10410
      cd/m2 at 10 V, a luminous efficiency of 17.47 cd/A, a power efficiency of 7.19
      Im/W, an external quantum efficiency of 6.27% at 20 mA/cm2, respectively, and
      CIE(x,y) coordinates of (0.51, 0.48) at 10 V. Furthermore, a red OLED using
      dopant 2, with CIE(x,y) coordinates of (0.61, 0.39), exhibited a maximum
      luminance of 5797 cd/m2 at 10 V, a luminous efficiency of 11.43 cd/A at, a power
      efficiency of 4.12 Im/W, and an external quantum efficiency of 6.62% at 20
      mA/cm2, respectively.

PMID- 22852384
TI  - Construction and performance evaluation of mediator-less microbial fuel cell
      using carbon nanotubes as an anode material.
AB  - A microbial fuel cell (MFC) is a device that converts chemical energy to
      electrical energy using the catalytic reaction of microorganisms. We investigated
      the performance of mediator-less MFC with carbon nanotubes (CNTs)/graphite felt
      composite electrodes. The addition of CNTs to a graphite felt electrode increases
      the specific surface area of the electrode and enhances the charge transfer
      capability so as to cause considerable improvement of the electrochemical
      activity for the anode reaction in a MFC. The performance of the MFC using
      CNTs/graphite felt electrode has been compared against a plain graphite felt
      electrode based MFC. A CNTs/graphite felt electrode showed as high as 15%
      increase in the power density (252 mW/m2) compared to graphite felt electrode
      (214 mW/m2). The CNTs/graphite felt anode therefore offers good prospects for
      application in MFCs.

PMID- 22852385
TI  - Preparation and characterization of high molecular weight low bandgap polymers
      based on poly(2,7-carbazole)s for organic solar cells.
AB  - We report the PCDTBT {Poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2
      thienyl-2',1',3'-benzothiadiazole)]}, an alternating copolymer of 2,7-carbazole
      and dithienyl-2,1,3-benzothiazole, has high molecular weight and narrow molecular
      weight distribution. Our PCDTBT can be successfully prepared as good yield by
      using tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] catalyst instead of
      Pd2dba3/P(o-Tol)3 catalyst. From the UV/Vis absorption spectroscopy, we can
      observe that absorption bands of PCDTBT are bathochromically shifted by
      increasing the molecular weight, that is to say, our high molecular weight PCDTBT
      can absorb much longer wavelength light compare to low molecular weight PCDTBT.
      The best performance can be obtained from device based on the mixture of PCDTBT
      (polymer-30) and PC70BM {[6,6]-phenyl C71-butyric acid methyl ester} (1:4) as an
      active layer, which shows 4.50% of PCE with 10.1 mA/cm2 of short-circuit current
      density (J(SC)), 0.85 V of open-circuit voltage (V(OC)), and 52.3% of fill factor
      which is very similar with Leclerc's published result.

PMID- 22852386
TI  - All printed edge-triggered register using single walled carbon nanotube-based
      thin film transistor.
AB  - We have studied the fabrication of Single Walled Carbon Nanotube (SWNT)-based
      Thin Film Transistors (TFTs) using Roll-to-Roll (R2R) gravure printer and inkjet
      printer on PET foils to show the possibility of printed electronics in point of
      mass production and low cost. In this paper, for realization of all printed multi
      bits digital circuit, all printed positive-edge triggered master-slave D flip
      flop (DFF) was fabricated on PET foil using printed SWNT TFTs. The printed DFF,
      consists of 8 NAND gates and 4 inverters, exhibit propagation delay of 75 ms at
      the input clock signal of 5 Hz.

PMID- 22852387
TI  - InGaN-based nano-pillar light emitting diodes fabricated by self-assembled ITO
      nano-dots.
AB  - InGaN/GaN based nano-pillar light emitting diodes (LEDs) with a diameter of 200
      300 nm and a height of 500 nm are fabricated by inductively coupled plasma
      etching using self-assembled ITO nano-dots as etching mask, which were produced
      by wet etching of the as-deposited ITO films. The peak PL intensity of the nano
      pillar LEDs was significantly higher than that of the as-grown planar LEDs, which
      can be attributed to the improvement of external quantum efficiency of the nano
      pillar LEDs due to the large sidewall of the nano-pillars. We have also
      demonstrated electrical pumping of the InGaN/GaN based nano-pillar LEDs with a
      self-aligned TiO2 layer as a passivation of sidewall of the nano-pillars.

PMID- 22852388
TI  - Synthesis and characterization of anthracene derivative for organic field-effect
      transistor fabrication.
AB  - Here we report on the synthesis and characterization of anthracene derivative for
      solution processable organic field-effect transistors. The transistor devices
      with bottom-contact geometry provided a maximum field-effect mobility of 3.74 x
      10(-4) cm2 V(-1) s(-1) as well as current on/off ratio of 5.05 x 10(4) and low
      threshold voltage. Structural information in the solid state is obtained by
      thermal analysis and two-dimensional wide angle X-ray scattering (2D-WAXS). From
      the 2D-WAXS, it is clear that the planes of anthracene rings and benzene ring of
      the molecule are different in solid state. We assume similar arrangement in the
      thin-film which limit the effective hopping and thus charge mobility.

PMID- 22852389
TI  - An alkyl spacer effect on the structure of 4-fluorobenzenethiol and 4
      fluorobenzenemethanethiol self-assembled monolayers on Au(111).
AB  - Self-assembled monolayers (SAMs) formed by the adsorption of 4-fluorobenzenethiol
      (4-FBT) and 4-fluorobenzenemethanethiol (4-FBMT) on Au(111) were examined by
      scanning tunneling microscopy (STM) to understand the effect of a flexible
      methylene spacer between the sulfur head-group and phenyl group and the effect of
      solution temperature on the formation and structure of the SAMs. Although the
      adsorption of 4-FBT on Au(111) at room temperature for 24 h generated only
      disordered phase SAMs containing gold adatom islands, 4-FBT at 75 degrees C for 2
      h formed mixed SAMs: disordered phases and ordered (2 x 12?(2))R10 degrees
      superlattice with a rectangular unit cell containing six adsorbed molecules. On
      the other hand, SAMs formed from 4-FBMT, with a methylene spacer, at room
      temperature for 24 h on Au(111) had irregularly ordered phases containing
      uniformly distributed VIs with lateral dimensions of 2-5 nm; SAMs formed from 4
      FBMT at 75 degrees C for 2 h were composed of slightly improved ordered phases
      and larger VIs with lateral dimensions of 5-12 nm as a result of Ostwald
      ripening. From this study, we found that the methylene spacer plays an important
      role in controlling the structure of SAMs formed from p-substituted fluorinated
      aromatic thiols.

PMID- 22852390
TI  - Synthesis and characterization of conjugated low band-gap terpolymers
      incorporating carbazole for photovoltaic application.
AB  - A series of photoactive conjugated low band-gap copolymer (CPSB) and terpolyemrs
      (TPSBCz-n, n = 1 to 4) based on N-alkyl carbazole, 4,4'-dialkyl dithienosilole,
      and bezothiadiazole were synthesized. The copolymer and terpolymers were built
      with the fraction of the carbazole unit varied for 0, 2.5, 5, 10 and 25 mol%.
      Among the mixtures, the composition of 25 wt% of terpolymer bearing 10 mol.% of
      the carbazole unit, TPSBCz-3, and 75 wt% of C71-PCBM found a power conversion
      efficiency of 0.86% with a open-circuit voltage of 0.59 V, the short-circuit
      current of 4.85 mA and fill factor of 0.30 under AM 1.5 spectral illumination.
      Our findings suggest that terpolymer bearing low concentration of carbazole lead
      to a high power conversion efficiency with improved the short-circuit current due
      to hole mobility enhancement effect of carbazole unit.

PMID- 22852391
TI  - Patterning of TiO2 particles on poly(dimethyl siloxane) films by using proton
      irradiation and liquid-phase deposition process.
AB  - Micropatterning of titanium dioxide (TiO2) on the surface of thin poly(dimethyl
      siloxane) (PDMS) films was described by means of proton irradiation and liquid
      phase deposition (LPD) techniques. The surface of thin PDMS films was irradiated
      with accelerated proton ions through a pattern mask in the absence or presence of
      oxygen in order to create hydrophilically/hydrophobically patterned surfaces. The
      results of the surface analysis revealed that the PDMS films irradiated at the
      fluence of 1 x 10(15) ions cm-2 in the presence of oxygen showed the highest
      hydrophilicity. The LPD of TiO2 particles on the patterned PDMS film surface
      showed a selective deposition of TiO2 on the irradiated regions, leading to well
      defined TiO2 micropatterns. The crystal structure of the formed TiO2 films was
      found to be in an anatase phase by X-ray diffraction analysis. This process can
      be applied for patterning various metal and metal oxide particles on a polymer
      substrate.

PMID- 22852392
TI  - Theoretical studies of blue phosphorescent iridium(III) complexes with
      phenylpyrazole and phosphines.
AB  - New blue emitting mixed ligand iridium(III) complexes comprising one
      cyclometalating, two phosphines trans to each other such as
      Ir(dppz)(PPhMe2)2(H)(C1) and Ir(dppz)(PPhMe2)2(H)(CN), [dppz = 3,5
      Diphenylpyrazole] were studied to tune the phosphorescence wavelength to the deep
      blue region and to enhance the luminescence efficiencies. To achieve deep blue
      emission and increase the emission efficiency, the following must occur: (1)
      substitution of phenyl group on the 3-position of the pyrazole ring that lower
      the triplet energy enough that the quenching channel is not thermally accessible,
      (2) changing ancillary ligands coordinated to iridium atom to phosphine and cyano
      groups known as very strong field ligands. Using the density functional theory
      (DFT) and time-dependent DFT method calculations on the ground and excited states
      of the complexes, we have studied how the ancillary ligand influences the
      emission peak as well as MLCT transition efficiency. It is showed that the strong
      field ancillary ligand such as CN, PPhMe2 alters the energy gap mainly by
      changing the highest occupied molecular orbitals (HOMO) energy level. Their
      inclusion in the coordination sphere can increase the energy gap to achieve the
      hypsochromic shift in emission color and also lower the triplet energy level to
      avoid the thermal quenching.

PMID- 22852393
TI  - Low-temperature processing method of preparing for transparent graphene oxide
      electrode film with better electrical properties.
AB  - Graphene oxide films were prepared by a facile ball milling process. The milling
      time and the amount of the acryl type polymer dispersion agent were controlled to
      obtain well dispersed graphene oxide solution in ethanol. Consequently, the
      transparent and conducting graphene oxide film which had 69% transmittance and
      1.5 x 10(6) ohm/sq surface resistance was produced by bar coating the solution on
      a PET substrate. The electrical property of the graphene oxide film could be
      further improved to 2.1 x 10(5) ohm/sq by hydrazine vapor reduction.

PMID- 22852394
TI  - Synthesis and characterization of novel p-type alkyl bithiophene end-capped
      anthracene and naphthalene derivatives for organic thin-film transistors.
AB  - New semiconductors having naphthalene and anthracene cores with hexylated
      bithiophene side units, 2,6-bis(5'-hexylbithiophen-2'-yl)naphthalene (HBT-NA) and
      2,6-bis(5'-hexylbithiophen-2'-yl)anthracene (HBT-AN), were synthesized. HBT-AN
      and HBT-NA were characterized using FT-IR, 1H-NMR, Mass spectrum and elemental
      analysis. HBT-AN and HBT-NA showed well ordered crystalline with high thermal
      stabilities as evidenced by 5% weight loss at 447 degrees C for HBT-AN and 434
      degrees C for HBT-NA. The closed packed structures between adjacent molecules
      were observed by studying UV-visible and photoluminescence (PL) in solution and
      film. The HOMO energy levels of HBT-NA and HBT-AN were found to be 5.47 eV and
      5.42 eV, respectively. HBT-NA exhibits hole mobility of 8.4 x 10(-2) cm2Ns and
      on/off ratio of 5.6 x 10(5). HBT-AN shows 5.2 x 10(-2) cm2Ns and on/off ratio of
      1.0 x 10(5).

PMID- 22852395
TI  - Preparation and characterization of graphene nanoplatelets from natural graphite
      via intercalation and exfoliation with tetraalkylammoniumbromide.
AB  - A new method for the preparation of graphene nanoplatelets (GNP) from graphite
      intercalation compounds (GICs) was investigated. Donor-type ternary GICs of
      natural graphites, lithium ions and tetrahydrofurane (NG-Li-THF) were synthesized
      via a solution process, with the lithium ions in the GICs then exchanged with
      different tetra alkyl ammonium cations to expand the interlayer distance (d
      spacing) of these GICs. Microwave irradiation of these GICs resulted in the
      exfoliation of GICs, forming so-called 'worm-like exfoliated graphites.'
      Sonication of the worm-like exfoliated graphites in acetone resulted in GNPs with
      different aspect ratios. Powder X-ray diffractometry, scanning electron
      microscopy and transmission electron microscopy were employed to characterize the
      GICs and GNPs. It was found that the ion-exchange of NG-Li-THF increased the
      volume expansion ratios, and the molecular structure of the tetra alkyl ammonium
      cations affected the aspect ratios of the GNPs after exfoliation.

PMID- 22852396
TI  - Controlled transformation of CdTe nanoparticles into nanoribbons via self
      assembling process.
AB  - CdTe nanorribons were successfully synthesized from individual nanoparticle. Slow
      oxidation of Te(2-) in CdTe nanoparticles resulted in the assembly of ribbons
      consisting of several layers of individual nanocrystals. The light-controlled
      self-assembly of CdTe nanoparticles led to twisted ribbons with variable pitch.
      Transmission electron microscopy, scanning electron microscopy, and atomic force
      microscopy were performed to characterize the synthesized nanostructures. The
      suggested synthetic procedure provides a viable pathway for the fabrication of
      nanomaterials with helical conformations.

PMID- 22852397
TI  - Structural and optical properties of chemically deposited CuInSe2 thin film in
      acidic medium.
AB  - Thin films of nanocrystalline CuInSe2 were prepared on glass substrates using
      chemical bath deposition in acidic medium at room temperature. Thickness of the
      chemically deposited CuInSe2 thin films was approximately 100 nm which composed
      of closely packed irregular grains of approximately 100-120 nm in diameter. X-ray
      diffraction pattern of CuInSe2 thin films showed nanocrystalline structure with
      (112) preferential orientation. The films exhibited faint black and direct band
      gap energy was 0.96 eV.

PMID- 22852398
TI  - Synthesis and properties of the diruthenium(II) complexes with diimine-linked
      polypyridine bridges.
AB  - The diruthenium complexes, [(bpy)2Ru(II)-(bpy-DPDA)-Ru(II)(bpy)2][PF6]4 3, (bpy:
      2,2'-bipyridiyl; bpy-DPDA: Bis(2,2'-dipyridylketenylidene)-N,N-1,4
      phenylenediamine}, and [(bpy)2Ru(II)-(Dbpy-DPDA)-Ru(II)(bpy)2][PF6]4 4 {Dbpy
      DPDA: Bis(2,2'-dipyridyl ketenylidene)-N,N-1,1'-(4,4'-diphenylene)diamine}, were
      prepared by the reaction of (bpy)2Ru(II)Cl2 with diimine-linked polypyridine
      bridges. These complexes were characterized by NMR, IR, UV/VIS, PL and cyclic
      voltammetry. In the 13C-NMR spectra of 3 and 4, the carbon peaks of the Schiff
      Bases (>C=N-) were shifted to lower fields, and emissions were observed at 689
      and 693 nm with quantum yields of 0.004 and 0.006, respectively. The
      electrochemistry of complexes 3 and 4 showed four-reversible waves (one oxidation
      wave and three reduction waves). The electrochemically measured band gaps for
      complexes 3 and 4 were 2.01 and 2.10 eV, respectively.

PMID- 22852399
TI  - Influence of surface modification of polyethylene terephthalate film on inkjet
      printing of Pd(II) catalytic ink.
AB  - To form the Cu circuit with electroless plating method on polyethylene
      terephthalate (PET) film, the Pd catalyst layer was formed by printing and liquid
      phase reduction of the Pd(II) ink on surface modified polyethylene terephthalate
      (PET) film. The Pd(II) ink could be obtained by hydrolysis of PdCl2 and NH4Cl
      solution and added with a stabilizing agent. To investigate the optimal printing
      characteristics by surface modification, the PET film was immersed into the KOH
      solution. The contact angle on surface of PET film greatly depended on the
      temperature and the concentration of the KOH solution. The printing of Pd(II) ink
      and Cu electroless plating characteristics were most excellent when the surface
      modification was carried out for 60 min at 60 degrees C in the 5-10 M KOH
      solution.

PMID- 22852400
TI  - An aromatic imine group enhances the electro-luminescence efficiency and color
      purity of blue emitter for organic light emitting diodes.
AB  - DPBP-EPY has the same structure with DPBP-EIF, one of blue-light-emitting
      materials, except their cores, in which the former has two imine groups, but the
      latter has only carbon-containing groups. The electro-optical properties
      modulated by the adoption of the different core structures were systematically
      examined. It was confirmed that the maximum values in the UV-visible and PL
      spectra of DPBP-EPY were about 19-46 nm red-shifted from those of DPBP-EIF due to
      the electron-withdrawing effect of the imine groups whether in solution or in
      solid. In addition, in case of DPBP-EPY where imine group is substituted, LUMO
      level of DPBP-EPY decreased while HOME level did not show any significant change.
      Furthermore, the results of the non-doped OLED device built with these two
      materials for an emitting layer indicated that DPBP-EPY needed about 2 V lower
      operation-voltage, and produced higher quantum yield than DPBP-EIF. In
      particular, it was shown that DPBP-EPY emitted purer and deeper blue-light with
      CIE coordinate (0.157,0.131) than DPBP-EIF with CIE coordinate is (0.179, 0.191).

PMID- 22852401
TI  - Carbazole/triarylamine based polymers as a hole injection/transport layer in
      organic light emitting devices.
AB  - This study examined the influence of the charge injection barriers on the
      performance of organic light emitting diodes (OLEDs) using polymers with a
      stepwise tuned ionization potential (I(p) approximately -5.01 - -5.29 eV) between
      the indium tin oxide (ITO) (phi approximately -4.8 eV) anode and tris(8
      hydroxyquinolinato) aluminium (Alq3) (I(p) approximately -5.7 eV) layer. The
      energy levels of the polymers were tuned by structural modification. Double layer
      devices were fabricated with a configuration of ITO/polymer/Alq3/LiF/Al, where
      the polymers, Alq3, and LiF/Al were used as the hole injection/transport layer,
      emissive electron transport layer, and electron injection/cathode, respectively.
      Using the current density-voltage (J-V), luminescence-voltage (L-V) and
      efficiencies in these double layer devices, the device performance was evaluated
      in terms of the energy level alignments at the interfaces, such as the hole
      injection barriers (phi(h)(iTO/polymer) and phi(h)(polymer/Alq3)) from ITO
      through the polymers into the Alq3 layer, and the electron injection barrier
      (phi(e)(polymer/Alq3) or electron/exciton blocking barrier) at the polymer/Alq3
      interface.

PMID- 22852402
TI  - Synthesis and characterization of regioregular alkyl-substituted poly(3,4
      ethylenedioxythiophenes).
AB  - In order to increase the solubility of PEDOT, we introduced an alkyl chain into
      polymer backbone. Depending on the position of the alkyl bond, the steric
      hindrance between the alkyl chains can also leads to regioregularity in the
      polymer. The regioregular polymers can easily occur self-assembly, both in
      solution and in the solid state, resulting in highly ordered two- and three
      dimensional polymer architectures. A series of soluble regioregular alkyl
      substituted PEDOTs were synthesized using the Grignard Metathesis (GRIM) for the
      purpose of study on regiorandom and regioregular PEDOT. The ethylene proton
      adjacent to the oxygen atom of regioregular methoxydodecyl-PEDOT appears at 3.51
      ppm, whereas the corresponding peak of regiorandom methoxydodecyl-PEDOT appears
      at 3.42 ppm.

PMID- 22852403
TI  - Symmetric long alkyl chain end-capped anthracene derivatives for solution
      processed organic thin-film transistors.
AB  - Three new anthracene derivatives, 2,6-bis(4-decylphenyl)anthracene (DDPAnt), 2
      decyl-5-(2-(5-decylthiophen-2-yl)anthracen-6-yl)thiophene (DDTAnt), and 2,6-bis(4
      decyloxy phenyl) anthracene (DDPXAnt) were synthesized by Suzuki cross-coupling
      reaction. The obtained oligomers were characterized by 1H NMR, FT-IR, Mass, UV
      visible spectroscopy, cyclovotammetry, differencial scanning calorimetry, and
      thermogravimetric analysis. The thermal studies show that these oligomers are
      stable up to 400 degrees C. The solution processed OTFTs were fabricated using
      synthesized oligomers by spin-coating and drop casting processes on Si/SiO2.
      OTFTs based on DDPAnt showed the mobility of 7.6 x 10(-3) cm2/Vs and on/off ratio
      of 10(5).

PMID- 22852404
TI  - Synthesis and characterization of silver nanoparticle composite with poly(p-Br
      phenylsilane).
AB  - The one-pot synthesis and characterization of silver nanoparticle-poly(p-Br
      phenylsilane) composites have been carried out. The conversion of silver(+1) salt
      to stable silver(0) nanoparticles is promoted by poly(p-Br-phenylsilane), Br-PPS
      possessing both possible reactive Si-H bonds in the polymer backbone and C-Br
      bonds in the substituents. The composites were characterized using XRD, TEM, FE
      SEM, and solid-state UV-vis analytical techniques. TEM and FE-SEM data show the
      formation of the composites where large number of silver nanoparticles (less than
      30 nm of size) are well dispersed throughout the Br-PPS matrix. XRD patterns are
      consistent with that for fcc-typed silver. The elemental analysis for Br atom and
      the polymer solubility confirm that the cleavage of C-Br bond and the Si-Br
      dative bonding were not occurred appreciably at ambient temperature. Nonetheless,
      TGA data suggest that some sort of cross-linking was occurred at high
      temperature. The size and processability of such nanoparticles depend on the
      ratio of metal to Br-PPS. In the absence of Br-PPS, most of the silver particles
      undergo macroscopic aggregation, which indicates that the polysilane is necessary
      for stabilizing the silver nanoparticles.

PMID- 22852405
TI  - Poly(glycidyl methacrylate-acrylonitrile)-based polymeric electrolytes for dye
      sensitized solar cell applications.
AB  - Poly(glycidyl methacrylate-acrylonitrile) P(GMA-AN) copolymer was synthesized and
      used as a polymer electrolyte in dye-sensitized solar cells (DSSCs). P(GMA-AN)
      based polymer electrolyte is obtained by adding 1-methyl-3-propylimidazolium
      iodide (PMII) as a room temperature ionic liquid (RTIL), tetrabutylammonium
      iodide (TBAI), iodide (I2) as the source of redox couple (I3(-)/I(-)) in order to
      improve the power conversion efficiency (PCE) by addition of optimized
      plasticizer contents such as ethylene carbonate (EC) and propylene carbonate (PC)
      in an acetonitrile solvent. These polymer electrolyte results revealed that more
      stable photovoltaic performance such as PCE of 4.97% with enhanced short-circuit
      current density (J(SC), 10.42 mA/cm2) and open circuit voltage (V(OC), 0.75 V)
      and fill factor (FF) of 0.63 under standard light intensity of 100 mW/cm2,
      irradiation of AM 1.5 sunlight. It is expected that these polymer electrolyte is
      an attractive alternative to liquid electrolytes for the fabrication of the long
      term stable DSSCs.

PMID- 22852406
TI  - Photothermal properties of inorganic nanomaterials as therapeutic agents for
      cancer thermotherapy.
AB  - In recent years, gold (Au) nanoparticles (NPs) and single-walled carbon nanotubes
      (SWCNTs) have attracted significant attention as potent therapeutic agents for
      cancer thermotherapy. In this paper the photothermal properties of inorganic
      nanomaterials including porous silicon (PSi), titania (TiO2) nanotubes (NTs),
      TiO2 NPs, and multiwalled carbon nanotubes (MWCNTs), Au NPs and SWCNTs have been
      systematically investigated. PSi shows by far the largest temperature rise
      (deltaT), TiO2 NTs the second largest deltaT, and MWCNTs the smallest deltaT upon
      exposure to near-infrared (NIR) laser. The high photothermal effect of PSi has
      been found to be attributed to the high absorbance and the high surface-to-volume
      ratio due to the numerous micropores in PSi In addition, the factors affecting
      the photothermal effects of nanomaterials have been discussed. Our results
      suggest that PSi and TiO2 NTs are also potential therapeutic agents for cancer
      thermotherapy with excellent photothermal properties as well as high
      biocompatibility.

PMID- 22852407
TI  - High efficiency new hole injection materials for organic light emitting diodes
      based on dimeric phenothiazine and phenoxazine moiety derivatives.
AB  - New hole injection materials for organic light emitting diodes (OLEDs) based on
      phenothiazine and phenoxazine were synthesized, and the electro-optical
      properties of synthesized materials were examined by through UV-visible (UV-vis),
      photoluminescence (PL) spectrum and cyclic voltammetry (CV). 1-BPNA-t-BPBP and 1
      BPNA-t-BPBPOX showed T(g) of 127 and 200 degrees C, which are higher than that
      (110 degrees C) of 2-TNATA, a commercial hole injection layer (HIL) material. The
      highest occupied molecular orbital (HOMO) level of the synthesized materials of 1
      BPNA-t-BPBP and 1-BPNA-t-BPBPOX were 4.97 and 4.91 eV, indicating values well
      matched between HOMO (4.8 eV) of ITO and HOMO (5.4 eV) of NPB, hole transporting
      layer (HTL) material. As a result of using the synthesized materials in OLED
      device as HIL, 1-BPNA-t-BPBPOX of 2.43 Im/W was higher than 2-TNATA of 1.98 Im/W
      and 1-BPNA-t-BPBP of 1.39 Im/W in power efficiency. These results indicated that
      1-BPNA-t-BPBPOX shows higher excellent power efficiency which is about 18%
      improved over 2-TNATA a commercial HIL material.

PMID- 22852408
TI  - Synthesis and properties of a water-soluble ionic conjugated polymer with
      carboxylic acids.
AB  - A new water-soluble ionic conjugated polymer, poly[N-(carboxymethyl)-2
      ethynylpyridinium bromide], was prepared by the activated polymerization of 2
      ethynylpyridine by using bromoacetic acid. This polymerization proceeded well in
      mild reaction conditions without any additional initiator or catalyst. The
      polymer structure was characterized by various instrumental methods to have a
      conjugated polymer backbone system with the designed functional groups. The
      photoluminescence spectrum of polymer showed that the PL peak is located at 603
      nm corresponding to the photon energy of 2.06 eV. The cyclovoltammograms of
      polymer exhibited the irreversible electrochemical behaviors between the
      oxidation and reduction peaks. The oxidation current density of polymer versus
      the scan rates is approximately linear relationship in the range of 30 mV/sec-150
      mV/sec. It was found that the kinetics of the redox process of polymer is almost
      controlled by the reactant diffusion process from the oxidation current density
      of polymer versus the scan rates.

PMID- 22852409
TI  - Fluorometric detection of lectin with water-soluble hyperbranched conjugated
      polymer using mannose mediation.
AB  - A water-soluble hyperbranched polymer containing boronic acid groups at the ends
      of the polymer, which are capable of binding to diol-containing mannose, was
      syntheized. The hyperbranched polymer was prepared by a palladium-catalyzed
      Suzuki cross-coupling reaction using the tribromo monomer for the hyperbranched
      type structure. The water-soluble hyperbranched polymer (HP) exhibited enhanced
      fluorescence intensity upon exposure to lectin in the presence of mannose
      compared to other proteins, such as lysozyme and cytochrome c, because mannose
      plays a key role in binding both lectin and HP resulting in selective sensing
      toward lectin.

PMID- 22852410
TI  - New pyridopyrazine skelecton-based electron-transporting materials.
AB  - 2,3-Di(pyridine-2-yl)-7-(4-triphenylsilyl)phenyl)pyrido[2,3-b]pyrazine (DPPP)
      containing pyridopyrazine was designed and synthesized as a new electron
      transporting material for organic light-emitting devices (OLEDs). The obtained
      material forms homogeneous and stable amorphous film. The new synthesized showed
      the reversible cathodic reduction for hole blocking material and the low
      reduction potential for electron transporting material in organic EL devices. The
      molecule possess excellent thermal stability with glass transition temperature
      (T(g)) of 115 degrees C in nitrogen. DNTPD (60 nm)/NPD (30 nm)/CBP:Irppy 6% (40
      nm)/BAIq (10 nm)/ETL (30 nm)/LiF (0.5 nm)/Al structured device were fabricated
      using DPPP as electron transport material. The maximum luminance reached at 25000
      cd/m2. The current efficiency was 10.9 cd/A even high current.

PMID- 22852411
TI  - Highly efficient phosphorescent organic light emitting diodes based on
      iridium(III) complex with bulky substituent spacers.
AB  - We developed highly efficient phosphorescent organic light emitting diodes
      (PHOLEDs) using iridium(III) complex, fac-tris[4-methyl-2-2(4'
      trimethylsilylphenyl)pyridine] [Ir(msippy)3]. PHOLEDs based on Ir(msippy)3
      complex exhibit the yellowish-green emission with CIE color coordinates of
      (0.31,0.64). These device performances were compared with those of the green
      emitting Ir(ppy)3-based devices. The higher external quantum efficiency (EQE) of
      25.6% and the current efficiency of 84.4 cd/A were achieved for Ir(msippy)3-based
      device. The results show that the complete energy and/or charge transfer from the
      host to Ir(msippy)3 dopant in the emitting layer (EML) of the device resulted in
      the higher device efficiencies compared with those of Ir(ppy)3-based devices.

PMID- 22852412
TI  - Formation of flower-like Ag colloids using pulsed proton beam.
AB  - A new solution phase method is presented for the synthesis of "flower-like"
      silver nanomaterials using a pulsed proton beam irradiation process at room
      temperature. It was observed that the morphology of the prepared silver crystals
      was easily controlled by varying the number of exposures to the pulsed proton
      beam. The synthesized flower-like silver nanocrystals exhibited excellent surface
      enhanced Raman scattering (SERS) signals, which were attributed to the rough
      microstructures on the surface of the synthesized Ag crystals.

PMID- 22852413
TI  - Fabrication of gold nanoparticle/multi walled carbon nanotube hybrids by in situ
      reaction in water using poly(acryloyl beta-alanine).
AB  - Fabrication of a hybrid consists of gold nanoparticles and multi walled carbon
      nanotubes (MWCNTs) with the help of poly (amino acid) was investigated.
      Poly(acryloyl beta-alanine) was synthesized by precipitation polymerization in
      tetrahydrofuran. The polymers were used to form hybrids with MWCNTs in aqueous
      media. Subsequently, the polymer functionalized MWCNTs were fabricated by in situ
      formed gold nanoparticles. The fabrication by gold nanoparticles was confirmed by
      transmission electron microscopic analyses. The fabrication was attempted with
      different concentrations of lithium auric chloride solutions in the range of 0.1
      1.2 mM in water. The lower concentration of the gold precursor solution resulted
      in the formation and attachment of gold nanoparticles without aggregation while
      the higher concentration above 1.0 mM led to the aggregation of gold
      nanoparticles. The gold nanoparticles were observed only on the surface of MWCNTs
      and none was in the bulk aqueous phase.

PMID- 22852414
TI  - Effect of multi-dimensional ultraviolet light exposure on the growth of pentacene
      film and application to organic field-effect transistors.
AB  - We report on the multi-dimensional alignment of pentacene molecules on a
      poly(methyl methacrylate)-based photosensitive polymer (PMMA-polymer) and its
      effect on the electrical performance of the pentacene-based field-effect
      transistor (FET). Pentacene molecules are shown to be preferentially aligned on
      the linearly polarized ultraviolet (LPUV)-exposed PMMA-polymer layer, which is
      contrast to an isotropic alignment on the bare PMMA-polymer layer. Multi
      dimensional alignment of pentacene molecules in the film could be achieved by
      adjusting the direction of LPUV exposed to the PMMA-polymer. The control of
      pentacene molecular alignment is found to be promising for the field-effect
      mobility enhancement in the pentacene FET.

PMID- 22852415
TI  - Synthesis and characterization of borane-terminated poly(silole-co-germole) for
      the evaluation of luminescent PLED.
AB  - Codehydrocoupling (in the presence of various inorganic B, Al-hydrides) followed
      by borane-capping (with Ph2BCl) of 1,1-dihydrotetraphenylsilole (1) and 1,1
      dihydrotetraphenylgermole (2) (9:1 mole ratio) gave electroluminescent
      poly(silole-co-germole)s containing borane-ends (3) in high yield. The
      polymerization yield and molecular weight with Selectrides increase in the order
      L-Selectride < N-Selectride < K-Selectride. The molecular weights with B, Al
      inorganic hydrides increase in the order L-Selectride < Red-Al <N-Selectride < K
      Selectride < Super-Hydride. The borane-terminated copolymer 3 emits at 522 nm and
      are electroluminescent at 521 nm. The fluorescence quantum yield of 3 in toluene
      is (1.60 +/- 0.30) x 10(-2). The emission color is green and the maximum
      brightness of the device is 2,753 cd/m2 with a luminous efficiency of 0.66 Im/W.
      The borane end group exhibited no appreciable effect on the luminescent
      properties of 3. The electroluminescent copolymer 3 with boranyl end group is
      hence a good candidate for PLED fabrication.

PMID- 22852416
TI  - Large-scale synthesis of the controlled-geometry carbon coils by the manipulation
      of the SF6 gas flow injection time.
AB  - Carbon coils could be synthesized using C2H2/H2 as source gases and SF6 as an
      incorporated additive gas under thermal chemical vapor deposition system. Nickel
      catalyst layer deposition and then hydrogen plasma pretreatment were performed
      prior to the carbon coils deposition reaction. According to the different
      reaction processes, the injection time of SF6 gas flow was varied. The
      characteristics (formation density, morphology, and geometry) of the deposited
      carbon coils on the substrates were investigated according to the different
      reaction processes. Finally, the large-scale synthesis of carbon coils and their
      geometry control could be achieved merely by manipulating SF6 gas flow injection
      time. Three cases growth aspects were proposed according to SF6 gas flow
      injection time in association with the fluorine's characteristics for etching the
      materials or enhancing the nucleation sites.

PMID- 22852417
TI  - Synthesis and photophysical properties of two-photon absorbing spirofluorene
      derivatives.
AB  - New spirofluorene-based quadrupolar two-photon absorbing dyes having
      triphenylamine and N,N-dibutylaniline as electron donors at the end of molcules
      were designed and synthesized. The third-order nonlinear optical properties of
      these compounds were studied using a two-photon excited fluorescence method. They
      were found to have high two-photon absorption cross-section owing to extended
      conjugation of the spirofluorene moiety. The effect of varying the donor strength
      could be discerned by comparing the two compounds. They were successfully used as
      a photosensitizers for two-photon initiated polymerization of three-dimensional
      micro-objects.

PMID- 22852418
TI  - Islamic death rituals in a small town context in The Netherlands: explorations of
      a common praxis for professionals.
AB  - Islamic tradition tends to present death rituals in a quite univocal way, as the
      actual ritual practice shows to be far more diverse and flexible. This study
      focuses on the particular ritual of the cleansing of the deceased as it is
      practiced by a variety of Muslims in a small town context in The Netherlands. The
      presented vignettes are drawn on qualitative research data from interviews and
      (participant) observations. They are presented to draw attention to the different
      contexts that shape the religious and ritual practice of a variety of Muslims in
      The Netherlands. To develop an eye for this common praxis, it is important not
      only to be aware of the religious dimensions but also of the social dimensions.
      By offering insights into the actual practices it aims to offer tangible leads to
      professionals for a more tailor-made care for Muslim patients and their
      relatives.

PMID- 22852419
TI  - Healing components of a bereavement camp: children and adolescents give voice to
      their experiences.
AB  - This qualitative study is the follow-up to a quantitative controlled study which
      showed a decrease in childhood traumatic grief and posttraumatic stress disorder
      symptoms in parentally bereaved children participating in a bereavement camp. The
      purpose of this study was to identify the healing components of this camp model.
      Semi-structured interviews with 19 children and 13 parents/guardians were
      conducted 3 to 9 months after participation in the bereavement camp. Therapeutic
      Interventions and Traditional Camp Activities emerged as themes. The themes are
      discussed in relation to previous research as are limitations of the study and
      the implications for theory, practice, and future research.

PMID- 22852420
TI  - "A sound track of your life": music in contemporary UK funerals.
AB  - This article considers the role that music plays in contemporary UK funerals and
      the meaning that the funeral music has for bereaved families. It is based on
      findings from a recently completed study of 46 funerals funded by the UK Arts and
      Humanities Research Council. Music contributes to the public ceremony and the
      personal existential quest of the bereaved. It is important to both the content
      and process of the contemporary funeral, an event of deep cultural significance
      in our response as individuals and communities to death and the loss of a
      significant relationship. There is evidence that for many people, the music
      chosen and used also evokes and conveys their spirituality. Spirituality may not
      be intrinsic to the music but spiritual experience may result from the meaning
      that the music has for that particular person.

PMID- 22852421
TI  - Does superstition help? A study of the role of superstitions and death beliefs on
      death anxiety amongst Chinese undergraduates in Hong Kong.
AB  - Past research has shown that traditional Chinese death beliefs, which mostly
      consisted of superstitious thoughts, are related to death anxiety. However, other
      studies have shown that superstitions may help people cope with uncertainty and,
      therefore, reduce uncertainty-induced anxiety. The role of superstitions, whether
      related to heightened death anxiety or reduced death anxiety, is unclear. This
      study attempted to address the knowledge gap by examining the relationships among
      superstitions and Chinese death beliefs on death anxiety in the Chinese context.
      One hundred twenty-four undergraduates in Hong Kong completed measures of
      superstition (R-PBS), death anxiety (MFODS), and Chinese death beliefs scale.
      Superstition was found to be predictor of death anxiety, as expected. With
      superstitions highly prevalent in Chinese societies, the study has practical
      implications in end-of-life care, bereavement support, and death education in the
      Chinese context.

PMID- 22852422
TI  - Conversations, coping, & connectedness: a qualitative study of women who have
      experienced involuntary pregnancy loss.
AB  - The purpose of this qualitative study was to describe processes and strategies
      used by women to cope after pregnancy loss. Twenty women with a history of
      involuntary pregnancy loss were interviewed. All of the women were in the last
      month of a subsequent pregnancy, married or partnered, and most were EuroAmerican
      or Asian American and had completed college. Taped interviews, fieldnotes, and
      analytical notes were transcribed then subsequently coded and developed in
      individual or team sessions. Construction and confirmation of the categories and
      related themes derived from the data was a collaborative process. Three themes
      were revealed that described the coping behaviors used by the women: being
      myself, connecting with others, and avoiding and pretending. The core concept of
      connectedness and coping after involuntary pregnancy loss was further validated
      in this study. The purpose of this study was to describe processes and strategies
      that facilitate coping for 20 women, pregnant subsequent to an involuntary
      pregnancy loss (IPL). Involuntary pregnancy loss (IPL) refers to miscarriages,
      ectopic pregnancies, fetal deaths, and stillbirths (Van & Meleis, 2003). This
      current study was designed to replicate two prior qualitative studies, with
      African-American women, by the author (Patterson, 2000; Van, 2001). Based on the
      author's previous work, a theoretical framework entitled "A Model of Living with
      Grief after Pregnancy Loss" was constructed (Patterson, 2000). For the current
      study, a more diverse sample was used to potentially expand the applicability of
      the Model of Living with Grief after Pregnancy Loss to women who are of races
      other than African American.

PMID- 22852423
TI  - Hydrodynamic treatment of wastewater effluent flocs for improved disinfection.
AB  - Hydrodynamic forces generated by an orifice plate under low pressure were
      examined as a means of disrupting flocs, in order to improve disinfection of
      treated wastewater effluents. Changes in cavitation conditions were found to have
      little impact on the extent of particle breakage in this experimental setup. The
      rate of strain (flow rate divided by the hole radius cubed), however, was found
      to be the best predictor of floc breakage. Floc breakage was not affected by
      changes in floc concentration, but was very sensitive to differences between
      flocs collected from different sources. Larger flocs (90 to 106 microm) were
      broken apart to a greater extent than smaller ones (53 to 63 microm).
      Hydrodynamic treatment decreased the viability of bacteria associated with large
      flocs, and also increased the ultraviolet dose response by up to one log unit
      (i.e., a factor of ten). Subjecting final effluent wastewaters to hydrodynamic
      treatment, therefore, provides a treatment strategy for conditions in which the
      presence of flocs limits the level of disinfection that can be achieved.

PMID- 22852424
TI  - Microalgae growth using high-strength wastewater followed by anaerobic co
      digestion.
AB  - Integration of algal biofuel production to wastewater anaerobic digestion
      infrastructure has the potential to increase biogas production, decrease high and
      variable internal nitrogen loads, and improve sludge digestibility and
      dewaterability. In this research, two species of microalgae, Spirulina platensis
      and Chlorella sp., were grown on sludge centrate and a centrate and nitrified
      wastewater effluent mixture. Harvested algae were co-digested with waste
      activated sludge (WAS) at varying ratios. High-growth (6.8 g m(-2) x d(-1)),
      nitrogen (36.5 g m(-3) x d(-1)), and phosphorus (6.5 g m(-3) x d(-1)) uptake
      rates were achieved with Chlorella on centrate. No growth was observed with S.
      platensis under the same conditions; however, both organisms grew well on the
      centrate and effluent mixture. Co-digestion of algae with WAS improved volatile
      solids reduction. Although co-digestion with S. platensis improved biosolids
      dewaterability, Chlorella had a slight negative effect on dewaterability compared
      to WAS alone. The efficiency of energy conversion from photons to biogas
      generated from Chlorella was estimated at 1.4%.

PMID- 22852425
TI  - Effect of artificial aeration, temperature, and structure on nutrient removal in
      constructed floating islands.
AB  - To study the optimal performance characteristics and maximize the removal
      efficiency of contaminants by the constructed floating islands (CFIs), four kinds
      of parallel pilot-scale CFIs with different structures were set up outdoors to
      treat eutrophic water for approximately 6 months. The contribution of artificial
      aeration to nutrient removal on the basis of gas-water ratios was investigated,
      and the influences of the structure and temperature were evaluated
      simultaneously. It was noted that the nutrient removal rate of the multi-medium
      CFI was greater than those of others. In the four kinds of units, aeration could
      significantly increase the nutrient removal efficiency, and a gas-water ratio of
      10 was adequate for the relatively high removal of nutrients. Using the
      aforementioned gas-water ratio of 10 and a hydraulic residence time (HRT) of 2
      days, the mean removal efficiencies of the multi-medium CFI for NH3-N and total
      phosphorus were 71.7% and 63.6%, respectively-approximately twice as great as
      those in the non-aerated system. Furthermore, temperature was an important factor
      for nutrient removal in the multi-medium CFI. With the water temperature of >13
      degrees C and the HRT of 2.5 days, the mean removal efficiencies for NH3-N and
      total phosphorus were 87.6% and 83.5%, respectively, whereas the removal
      efficiency decreased significantly when the temperature was lower than 13 degrees
      C.

PMID- 22852426
TI  - Phosphate removal from digested sludge supernatant using modified fly ash.
AB  - The removal of phosphate in digested sludge supernatant by modified coal fly ash
      was investigated in this study. Modification of the fly ash by the addition of
      sulfuric acid could significantly enhance its immobilization ability. The
      experimental results also showed that adsorption of phosphate by the modified fly
      ash was rapid with the removal percentage of phosphate reaching an equilibrium of
      98.62% in less than 5 minutes. The optimum pH for phosphate removal was 9 and the
      removal percentage increased with increasing adsorbent dosage. The effect of
      temperature on phosphate removal efficiency was not significant from 20 to 40
      degrees C. X-ray diffraction and scanning electron microscope analyses showed
      that phosphate formed an amorphous precipitate with water-soluble calcium,
      aluminum, and iron ions in the modified fly ash.

PMID- 22852427
TI  - Selective removal of some polyhydric phenols from aqueous solution by ferric
      antimonate.
AB  - Ferric antimonate, a cation-exchanger, has been investigated as an adsorbent for
      the removal of phenol and polyhydric phenols from aqueous solution. It has been
      found that ferric antimonate in H+ form selectively adsorbs polyhydric phenols
      having hydroxyl groups on adjacent positions. While phenol, resorcinol, and
      quinol did not show any appreciable adsorption, catechol, pyrogallol, and gallic
      acid having hydroxyl groups on adjacent positions exhibited considerable
      adsorption on ferric antimonate. Batch equilibrium experiments were carried out
      to study the effect of contact time, initial concentration of phenolic compounds,
      and temperature on the adsorption of phenolic compounds on ferric antimonate. The
      equilibrium time was found to be 1.5 hours for gallic acid and pyrogallol and 2
      hours for catechol and salicylic acid. The adsorption data of the phenols at
      temperatures of 30 degrees, 40 degrees, and 50 degrees C have been described by
      Langmuir and Freundlich isotherm models. The best fit was obtained with the
      Langmuir model in the whole range of concentrations studied at all temperatures,
      indicating a monolayer adsorption onto a homogeneous adsorption surface. On the
      basis of the Langmuir isotherm, the maximum adsorption capacity of ferric
      antimonate for gallic acid, pyrogallol, catechol, and salicylic acid was found to
      be 3.915, 3.734, 2.397, and 2.758 mg/g, respectively at 30 degrees C. The maximum
      sorption capacity of ferric antimonate for the phenolic compounds studied is in
      the following order: gallic acid > pyrogallol > salicylic acid > catechol. The
      adsorption of phenolic compounds was found to decrease with an increase in
      temperature. Thermodynamic parameters like free energy, enthalpy, and entropy
      changes were calculated and discussed. The adsorption of polyhydric phenols on
      ferric antimonate is exothermic and spontaneous in nature.

PMID- 22852428
TI  - Effect of turbulence on the disintegration rate of flushable consumer products.
AB  - A previously developed model for the physical disintegration of flushable
      consumer products is expanded by investigating the effects of turbulence on the
      rate of physical disintegration. Disintegration experiments were conducted with
      cardboard tampon applicators at 100, 150, and 200 rotations per minute,
      corresponding to Reynold's numbers of 25,900, 39,400, and 52,900, respectively,
      which were estimated by using computational fluid dynamics modeling. The
      experiments were simulated with the disintegration model to obtain best-fit
      values of the kinetic and distribution parameters. Computed rate coefficients
      (ki) for all solid sizes (i.e., greater than 8, 4 to 8, 2 to 4, and 1 to 2 mm)
      increased strongly with Reynold's number or rotational speed. Thus, turbulence
      strongly affected the disintegration rate of flushable products, and the
      relationship of the ki values to Reynold's number can be included in mathematical
      representations of physical disintegration.

PMID- 22852429
TI  - Overflow risk analysis for designing a nonpoint sources control detention.
AB  - This paper presents a design method by which the overflow risk related to a
      detention for managing nonpoint pollutant sources in urban areas can be
      evaluated. The overall overflow risk of a nonpoint pollutant sources control
      detention can be estimated by inherent overflow risk and operational overflow
      risk. For the purpose of calculating overflow risk, the 3-parameter mixed
      exponential distribution is applied to describe the probability distribution of
      rainfall event depth. As a rainfall-runoff calculation procedure required for
      deriving a rainfall capture curve, the U.S. Natural Resources Conservation
      Service runoff curve number method is applied to consider the nonlinearity of the
      rainfall-runoff relation. Finally, the detention overflow risk is assessed with
      respect to the detention design capacity and drainage time. The proposed overflow
      risk assessment is expected to provide a baseline to determine quantitative
      parameters in designing a nonpoint sources control detention.

PMID- 22852430
TI  - Influence of near-to-nature stormwater management on the local water balance
      using the example of an urban development area.
AB  - Near-to-nature stormwater management aims at replicating the quasi-natural local
      water balance and preserving the ecosystem's integrity of affected waters.
      Surface waters in the urban areas of Trier-Petrisberg are managed by a separate
      sewer system in conjunction with a complex retention system. To investigate the
      effect of this alternative rainwater management practice on the local water
      balance, a differentiated discharge and groundwater monitoring network with a
      high spatio-temporal measurement resolution has been implemented within the
      watershed. Additional information regarding the proportion and spatial
      distribution of discharge-generating surfaces was provided through visual
      interpretation of aerial photographs. As a result of this analysis, groundwater
      levels were found to not be significantly affected by an increase of local sealed
      surfaces, and the ecologically-justifiable maximum discharge in the tributary was
      infrequently exceeded. Regarding further building development and climate change,
      the hydrological load capacity of the retention basins will provide effective
      rainwater management, even with respect to increasing precipitation intensities
      and frequencies.

PMID- 22852431
TI  - Full-Scale investigation of the influence of flow equalization and
      prefermentation on nitrification.
AB  - This article presents the findings on the effects of flow equalization and
      prefermentation on nitrification in a full-scale municipal plant. Existing
      primary clarifiers in one process train were modified for diurnal flow
      equalization and for a low-rate volatile fatty acid production. The performance
      of the biological process was compared with the parallel reference process train
      operated with conventional primary clarification. Only a few reports on the
      effects of equalization on nitrification have been published, but based on this
      limited knowledge, diurnal flow equalization was presumed to improve the
      nitrification performance. However, more constant flow conditions could not fully
      explain the improvements of autotrophic activity. The authors suggest that
      increased readily biodegradable organic matter played indirectly a role in
      nitrification performance. Moreover, stable flow conditions were reflected in
      improved sludge characteristics and offered, in addition to a levelling out of
      diurnal variations, a long-term buffer capacity against high hydraulic loadings.

PMID- 22852432
TI  - Analysis of the syntrophic anaerobic digestion of volatile fatty acids using
      enriched cultures in a fixed-bed reactor.
AB  - Volatile fatty acids (VFAs) are key intermediates in anaerobic digestion.
      Enriched acetogenic and methanogenic cultures were used for the syntrophic
      anaerobic digestion of VFAs in a continuous fixed-bed reactor at mesophilic
      conditions. The interactive effects of propionic (HPr), butyric (HBu), and acetic
      (HAc) acids were analyzed. Furthermore, hydraulic retention time (HRT) and
      methanogen-to-acetogen ratios (M/As) were investigated as the key microbiological
      and operating variables of VFA anaerobic degradations. Experiments were carried
      out based on central composite design (CCD) and results were analyzed using
      response surface methodology (RSM). Effluent concentrations of HPr, HBu, HAc, and
      biogas production rate (BPR) were directly measured as responses. The optimum
      conditions were found to be HPr = 1122.9 mg/L, HBu = 1792.4 mg/L, HAc = 1735.4
      mg/L, HRT = 21 hours, and M/A = 2.4 (corresponding to the maximum VFA removal and
      BPR). The results of verification experiments and predicted values from fitted
      correlations were in close agreement at a 95% confidence interval.

PMID- 22852433
TI  - Patterns of intimate partner violence in young adult couples: nonviolent,
      unilaterally violent, and mutually violent couples.
AB  - This study examined nonviolent (NV), unilaterally violent (UV), and mutually
      violent (MV) patterns of perpetrated intimate partner violence in relation to
      dyadic relationship quality and partner injury. The respondents were 1,294 young
      adult, Add Health partners (AHP) and their non-Add Health partners (NAHP), in
      dating, engaged, or in marital relationships, who were participants in Wave III
      of the National Longitudinal Study of Adolescent Health (Add Health). Using both
      partner reports of perpetration to classify intimate partner violence (IPV)
      patterns resulted in 25% of couples with a MV pattern, and 75% of couples with a
      UV pattern; among those couples (41%) reporting any perpetrated IPV. Results also
      showed poorer relationship quality and higher partner sensation-seeking scores
      among MV and UV couples when contrasted with NV couples. Those couples with MV
      patterns were more likely to contain partner injury than those with UV patterns.

PMID- 22852434
TI  - Links between childhood physical abuse and intimate partner aggression: the
      mediating role of anger expression.
AB  - Research linking childhood physical abuse (CPA) and adult intimate partner
      aggression (IPA) has focused on individuals without sufficient attention to
      couple processes. In this study, 109 couples reported on histories of CPA, IPA,
      and anger expression. Actor-partner interdependence model (APIM) was used to
      examine links between CPA and revictimization and perpetration of IPA, with anger
      suppression as a potential mediator. Women's CPA histories were associated with
      more physical aggression towards and more revictimization by partners. Men's CPA
      histories were only associated at the trend level with their revictimization.
      Anger suppression fully mediated the link between women's CPA and both
      revictimization and perpetration of IPA. Findings suggest that women with CPA
      histories are more prone to suppress anger, which leaves them at greater risk for
      revictimization and perpetration of IPA.

PMID- 22852435
TI  - Coping with dating violence as a function of violence frequency and solution
      attribution: a structural modeling approach.
AB  - This study presents a structural model of coping with dating violence. The model
      integrates abuse frequency and solution attribution to relate to college women's
      choices of coping strategies. Three hundred and twenty-four undergraduate women
      reported being targets of some physical abuse from a boyfriend and responded to
      questions regarding the abuse, their solution attribution, and their coping
      behaviors. Solution attribution mediated the relation between frequency of the
      abuse and coping. Abuse frequency had a positive effect on external solution
      attribution, and external solution attribution had a positive effect on the level
      of use of active coping, utilization of social support, denial, and acceptance.

PMID- 22852436
TI  - Does the age of offenders and victims in crime scenarios affect perceptions of
      crime seriousness and punitiveness among students?
AB  - The extent to which the age of the offender or the victim influences respondents'
      respective evaluations of crime seriousness and punitiveness has rarely been
      studied. This study hypothesizes that evaluations of the severity of offenses
      with intrapersonal and interpersonal social implications and the estimation of
      their punitiveness will be more serious when the offenses are performed by
      younger than by older offenders and less serious when they harm younger as
      opposed to older victims. Results from 129 undergraduate students who were
      administered the Multidimensional Social Transgressions Scale (MSTS) confirm the
      hypotheses. The findings are discussed in light of crime theories, social
      theories, and ageism studies.

PMID- 22852437
TI  - Workplace bullying, emotions, and outcomes.
AB  - This study examines emotional experiences as potential mediators between exposure
      to workplace bullying and job satisfaction, organizational commitment, and
      intention to leave the organization, respectively. A total of 5,520 respondents
      participated in the study. Drawing upon affective events theory (AET), the
      results show that emotions partly mediate these relationships and, hence, support
      the notion that emotions play a central part in the relationship between bullying
      and essential occupational outcomes.

PMID- 22852438
TI  - Exposure to harsh parenting and pornography as explanations for males' sexual
      coercion and females' sexual victimization.
AB  - Sexual violence against women is a major concern to researchers and policy
      makers, as well as to the general public. This study uses a sample of more than
      2,000 college students to investigate the extent to which exposure to harsh
      parenting practices and sexually explicit materials contributes to perpetration
      and victimization. Findings indicate that frequent corporal punishment in the
      family of origin combined with consumption of pornographic materials increased
      the probability that males reported engaging in coercive sexual practices. For
      females, both frequent corporal punishment and exposure to paternal hostility
      combined with consumption of pornographic materials were associated with higher
      levels of reported sexual victimization. These results provide increased
      understanding of the impact of pornography use among a nonclinical sample, as
      well as the consequences of experiencing harsh corporal punishment in one's
      family of origin, on the sexual victimization of females.

PMID- 22852439
TI  - Teachers bullied by students: forms of bullying and perpetrator characteristics.
AB  - The focus of this study is on the forms in which the bullying of school teachers
      by students manifests itself, the characteristics of the students who engage in
      the bullying, and the manner in which the students who engage in bullying behave
      in their own peer relationships. The data was gathered from primary and lower
      secondary school teachers by means of an Internet survey. The answers of 70
      teachers who had experienced bullying by their students are examined. The
      teachers had been exposed to different forms of bullying by students. They had
      typically been bullied by male students. In most cases, the bullying had been
      perpetrated by an individual student or a small group of students. According to
      the teachers' assessment, the majority of the students who bullied them also
      bullied their fellow students.

PMID- 22852440
TI  - Coping with obsessive relational intrusion and stalking: the role of social
      support and coping strategies.
AB  - This study investigated the extent to which social support mediates negative
      effects of stalking and obsessive relational intrusion (ORI) victimization. A
      survey of 1,068 respondents indicated that (a) ORI/stalking victimization is
      positively related to negative symptoms and trauma; (b) five different types of
      coping responses are positively related to negative symptoms; (c) four domains of
      social support reveal small but significant negative relationships with negative
      symptoms; and (d) females are more threatened by unwanted pursuit than male
      victims, and male pursuers are more threatening than female pursuers. Structural
      equation modeling indicates that the influence of ORI/stalking on negative
      symptoms is mediated by the use of coping strategies and the adequacy of social
      support. Discussion speculates on the functional theoretical value of coping and
      support processes in managing unwanted pursuit and stalking.

PMID- 22852441
TI  - Multidimensional self-esteem as a mediator of the relationship between sports
      participation and victimization: a study of African American girls.
AB  - The purpose of this study that focused on African American high school girls was
      threefold. First, the relationship of sports participation and victimization was
      explored. Second, the impact of sports participation on self-esteem was assessed.
      Third, the role of self-esteem and its disaggregated components (social
      acceptance, competence, and self-confidence) as mediators of the relationship
      between sports participation and victimization was examined. In accordance with
      the sport protection hypothesis, it was hypothesized that sports participation
      would be related to enhanced self-esteem and reduce victimization. Results
      suggest that sports participation appears to have some relationship to lower
      rates of victimization. There was also support for our assertion that sports
      participation was related to enhanced self-esteem. Finally, overall self-esteem
      and, specifically, the individual component competence mediated the relationship
      between sports participation and victimization.

PMID- 22852442
TI  - The fascia: the forgotten structure.
AB  - This paper examines the main characteristics of the human fascial system,
      considered in its three-dimensional continuity. To better understand the anatomy
      of the human fascial system, a simple diagram of the subcutaneous tissue must be
      borne in mind. From the skin to the deepest plane, we find the superficial
      fascia, dividing the subcutaneous tissue into two fibroadipose layers,
      superficial and deep, and the deep fascia, which envelops all the muscles of the
      body, showing different characteristics according to region. Under the deep
      fascia is the epimysium, occurring in the limbs and some regions of the trunk.
      Skin ligaments connect the superficial fascia to the skin and to the deep fascia,
      forming a three-dimensional network among the fat lobules. The typical features
      of the superficial and deep fasciae and their relationships to nerves, vessels
      and muscles are reported here, highlighting the possible role of the deep fascia
      in proprioception and peripheral motor coordination. The main features of the
      fasciae with imaging techniques are also discussed. This knowledge may contribute
      to clinicians' understanding of the myofascial system and the role which the deep
      fasciae may play in musculoskeletal dysfunctions.

PMID- 22852443
TI  - Sternalis "mystery" muscle and its clinical implications.
AB  - Sternalis is an anomalous muscle found occasionally in the anterior part of the
      thorax. During routine dissection sternalis muscle was found in a male cadaver.
      This rare anatomic variant is reported in 8% of the population. In the present
      case, the muscle was found bilaterally, placed obliquely on either side of the
      sternum. It originated by tendinous fibres from the lower costal cartilages and
      inserted to the manubriosternal junction. The right side muscle was well
      developed whereas the left one was reduced in size. The pectoralis major and
      minor were normal. The knowledge of sternalis is important for radiologists and
      surgeons.

PMID- 22852444
TI  - Retro-aortic left renal vein--an anatomic variation description and review of
      literature.
AB  - This study reports the presence of a retro-aortic renal vein on the left side
      draining into the inferior vena cava. This variation was observed during routine
      dissection in a female cadaver aged about 55 years. This variation is of
      importance because of its implications in renal transplantation, renal surgery,
      vascular surgery, uroradiology and gonadal surgeries. The knowledge of such
      variations can help the clinicians for its recognition and protection.

PMID- 22852445
TI  - Scotland's "wooden operator" William Smellie (1697-1763) and his counterpart in
      France Andre Levret (1703-1780): two great obstetricians and anatomists.
AB  - During the eighteenth century two great physicians, William Smellie and Andre
      Levret, instated maternity as a medical procedure. Although they had to face the
      negative criticism from women midwives of their time, nonetheless, through their
      work, they were recognized by the medical community as prominent obstetricians.
      With the expertise they gained they improved the forceps, while they thoroughly
      studied the anatomy of the pelvis. They passed their skills to their students who
      became the successors of their toil. Starting from two different countries and
      schools they both managed to shine within their science and leave behind a rich
      path.

PMID- 22852446
TI  - The upper respiratory tract of dolphins.
AB  - The functional anatomy of the respiratory system of dolphins has been scarcely
      studied. Specifically, the capacity of the system to resist pressure changes
      during diving has not been fully understood. Here we shortly describe the upper
      respiratory tract of dolphins based on three common species, the bottlenose
      dolphin Tursiops truncatus, the Risso's dolphin Grampus griseus, and the striped
      dolphin Stenella coeruleoalba. We emphasize the keymorphological features that
      represent evolutionary adaptations to life in the water, and, furthermore, also
      present a model of the tracheo-bronchial tree based on mechanical
      characterization and subsequent computational simulation of its biomechanical
      behaviour. Comparisons with the goat allowed us to determine how different
      structures may respond to diving-related pressure.

PMID- 22852447
TI  - Hic est locus ubi mors gaudet succurrere vitae: the utility of morphologic
      disciplines in the study of cetaceans' pathology.
AB  - The role played by morphologic disciplines and investigations in the study of the
      causes of death as well as of the pathology of cetaceans is of paramount
      relevance. In this respect, an absolutely paradigmatic example is that
      represented by Morbillivirus infections, which during the last 25 years have
      caused a number of dramatic epidemics among free-ranging pinnipeds and cetaceans
      worldwide.

PMID- 22852448
TI  - Carlo Ruini Junior (1530-1598) and the story of his 'Anotomia del cavallo et suoi
      rimedi'.
AB  - This report short news about Ruini family and the public life of Charles JR,
      author of the famous treatise 'Anotomia del cavallo e suoi rimedi'. The treatise
      is mentioned for his seven editions, the translated versions and the most
      sensational imitations

PMID- 22852449
TI  - Why life science needs its own Silicon Valley.

PMID- 22852450
TI  - Motivating salespeople: what really works.
AB  - No sales force consists entirely of stars; sales staffs are usually made up
      mainly of solid perfomers, with smaller groups of laggards and rainmakers. Though
      most compensation plans approach these three groups as if they were the same,
      research shows that each is motivated by something different. By accounting for
      those differences in their incentive programs, companies can coax better
      performance from all their salespeople. As the largest cadre, core performers
      typically represent the greatest opportunity, but they're often ignored by
      incentive plans. Contests with prizes that vary in nature and value (and don't
      all go to stars) will inspire them to ramp up their efforts, and tiered targets
      will guide them up the performance curve. Laggards need quarterly bonuses to stay
      on track; when they have only annual bonuses, their revenues will drop 10%,
      studies show. This group is also motivated by social pressure-especially from new
      talent on the sales bench. Stars tend to get the most attention in comp plans,
      but companies often go astray by capping their commissions to control costs. If
      firms instead remove commission ceilings and pay extra for overachievement,
      they'll see the sales needle really jump. The key is to treat sales compensation
      not as an expense to rein in but as a portfolio of investments to manage.
      Companies that do this will be rewarded with much higher returns.

PMID- 22852451
TI  - Cultural change that sticks.
AB  - When a major change initiative runs aground, leaders often blame their company's
      culture for pushing it off course. They try to forge ahead by overhauling the
      culture--a tactic that tends to fizzle, fail, or backfire. Most cultures are too
      well entrenched to be jettisoned. The secret is to stop fighting your culture-
      and to work with and within it, until it evolves in the right direction. Today's
      best-performing companies, such as Southwest Airlines, Apple, and the Four
      Seasons, understand this, say the authors, three consultants from Booz & Company.
      These organizations follow five principles for making the most of their cultures:
      1. Match strategy to culture. Culture trumps strategy every time, no matter how
      brilliant the plan, so the two need to be in alignment. 2. Focus on a few
      critical shifts in behavior. Wholesale change is hard; choose your battles
      wisely. 3. Honor the strengths of the existing culture. Every culture is the
      product of good intentions and has strengths; put them to use. 4. Integrate
      formal and informal interventions. Don't just implement new rules and processes;
      identify "influencers" who can bring other employees along. 5. Measure and
      monitor cultural evolution. Otherwise you can't identify backsliding or correct
      course. When the leaders of Aetna applied these rules while implementing a new
      strategy in the early 2000s, they reinvigorated the company's ailing culture and
      restored employee pride. That shift was reflected in the business results, as
      Aetna went from a $300 million loss to a $1.7 billion gain.

PMID- 22852452
TI  - Social values and health policy: a new international research programme.
AB  - PURPOSE: This editorial aims to outline the context of healthcare priority
      setting, and summarise each of the other ten papers in this special edition. It
      introduces a new multidisciplinary research programme drawing on ethics,
      philosophy, health economics, political science and health technology assessment,
      out of which the papers in this edition have arisen. DESIGN/METHODOLOGY/APPROACH:
      Key normative concepts are introduced and policy and research context provided to
      frame subsequent papers in the edition. FINDINGS: Common challenges of health
      priority-setting are faced by many countries across the world, and a range of
      social value judgments is in play as resource allocation decisions are made.
      Although the challenges faced by different countries are in many ways similar,
      the way in which social values affect the processes and content of priority
      setting decisions means that those challenges are resolved very differently in a
      variety of social, political, cultural and institutional settings, as subsequent
      papers in this edition demonstrate. How social values affect decision making in
      this way is the subject of a new multi-disciplinary research programme.
      ORIGINALITY/VALUE: Technical analyses of health priority setting are commonplace,
      but approaching the issues from the perspective of social values and conducting
      comparative analyses across countries with very different cultural, social and
      institutional contexts provides the content for a new research agenda.

PMID- 22852453
TI  - Social values in health priority setting: a conceptual framework.
AB  - PURPOSE: It is commonly recognized that the setting of health priorities requires
      value judgements and that these judgements are social. Justifying social value
      judgements is an important element in any public justification of how priorities
      are set. The purpose of this paper is to review a number of social values
      relating both to the process and content of priority-setting decisions.
      DESIGN/METHODOLOGY/APPROACH: A set of key process and content values basic to
      health priority setting is outlined, and normative analysis applied to those
      values to identify their key features, possible interpretations in different
      cultural and institutional contexts, and interactions with other values.
      FINDINGS: Process values are found to be closely linked, such that success in
      increasing, for example, transparency may depend on increasing participation or
      accountability, and "content" values are found often to be hidden in technical
      criteria. There is a complex interplay between value and technical components of
      priority setting, and between process and content values. Levels of economic
      development, culture and need will all play a part in determining how different
      systems balance the values in their decisions. ORIGINALITY/VALUE: Technical
      analyses of health priority setting are commonplace, but approaching the issues
      from the perspective of social values is a more recent approach and one which
      this paper seeks to refine and develop.

PMID- 22852454
TI  - Social value judgments in healthcare: a philosophical critique.
AB  - PURPOSE: The purpose of this paper is to consider some of the philosophical and
      bioethical issues raised by the creation of the draft social values framework
      developed to facilitate data collection and country-specific presentations at the
      inaugural workshop on "Social values and health priority setting" held in
      February 2011. DESIGN/METHODOLOGY/APPROACH: Conceptual analysis is used to
      analyse the term "social values", as employed in the framework, and its
      relationship to related ideas such as moral values. The structure of the
      framework (process and content values) is considered in light of current debate
      in philosophy and bioethics about the political and moral aims served by these
      kinds of values, and the extent to which they are either suited to, or sufficient
      for, the policy context. FINDINGS: There is much to be gained by engaging with
      the arguments presented in the philosophical literature in order to further
      refine the framework. The framework should remain neutral in respect of the
      importance of procedural values in different contexts and should be as inclusive
      as possible in respect of the principles it includes. Further development would
      be best served by taking a multidisciplinary approach. The framework could
      provide a valuable space in which future debates about procedural/substantive
      values can be considered. ORIGINALITY/VALUE: The paper brings philosophical and
      bioethics perspectives to bear on a new framework proposed for the analysis of
      social values in health priority setting. It identifies how such a practical,
      policy-focused framework might be informed by engagement with deeper, and often
      unresolved, questions or principle around resource allocation in health.

PMID- 22852455
TI  - Efficiency or equity: value judgments in coverage decisions in Thailand.
AB  - PURPOSE: The purpose of this paper is to analyse the roles of social values in
      the reform of coverage decisions for Thailand's Universal Health Coverage (UC)
      plan in 2009 and 2010. DESIGN/METHODOLOGY/APPROACH: Qualitative techniques,
      including document review and personal communication, were employed for data
      collection and triangulation. All relevant data and information regarding the
      reform and three case study interventions were interpreted and analysed according
      to the thematic elements in the conceptual framework. FINDINGS: Social values
      determined changes in the UC plan in two steps: the development of coverage
      decision guidelines and the introduction of such guidelines in benefit package
      formulation. The former was guided by process values, while the latter was shaped
      by different content ideals of stakeholders and policymakers. Analysis of the
      three interventions suggests that in allocating its resources to subsidise
      particular services, the UC authority took into account not only cost
      effectiveness, but also budget impacts, equity and solidarity. These social
      values competed with each other and, in many instances, the prioritisation of
      benefit candidates was not led solely by evidence, but also by value judgments,
      even though transparency was recognised as an ultimate goal of reform. RESEARCH
      LIMITATIONS/IMPLICATIONS: The study findings indicate room for improvement and
      for future research--the current conceptual framework is inadequate to capture
      all the crucial elements which influence health prioritisation, as well as their
      interactions with social values. ORIGINALITY/VALUE: The paper fills a gap in
      literature as it enhances understanding of the effects of social value judgments
      in real-life health prioritisation.

PMID- 22852456
TI  - Social values and healthcare priority setting in Korea.
AB  - PURPOSE: The purpose of this paper is to present the role of social values in
      setting healthcare priorities in Korea. DESIGN/METHODOLOGY/APPROACH: Using Clark
      and Weale's draft framework, Korean healthcare priority setting was analysed. The
      process values used were transparency, accountability, and participation, and the
      content values used were clinical effectiveness, cost effectiveness,
      justice/equity, solidarity and autonomy. FINDINGS: In the Korean health priority
      setting, it was found that multiple factors influence the decision-making
      process. Effectiveness and safety are the two most important values mentioned in
      the process. Cost-effectiveness is also considered in reimbursement decisions for
      new drugs since 2007. Recently, health technology assessment (HTA) has begun to
      change the social value system traditionally used in the Korean healthcare
      priority setting. ORIGINALITY/VALUE: The paper extends understanding of health
      priority setting in Korea, and how the interpretation and use of social values
      has changed over recent years.

PMID- 22852457
TI  - Social values and health priority setting in China.
AB  - PURPOSE: The purpose of this paper is to provide an overview of the
      organisational and procedural arrangements for healthcare reform in China, and
      describe the role of social values in the relevant decision-making process.
      DESIGN/METHODOLOGY/APPROACH: An analysis of recent developments aimed at
      achieving universal coverage in China was undertaken in the context of describing
      the influence of underlying social values. FINDINGS: The key underlying social
      value was found to be social solidarity. Other values were implicit rather than
      explicitly stated, and were subservient to the overall aim of comprehensive
      coverage. ORIGINALITY/VALUE: The paper shows that China is embarking on the
      largest-scale health reforms in the world. There is an eagerness to share
      experiences with other countries in an attempt to ensure the success of the
      reforms. There is an increasing understanding of the need to make the values
      underpinning the reforms more explicit and, in particular, those concerned with
      efficiency and appropriateness.

PMID- 22852458
TI  - Social values and health priority setting in England: "values" based decision
      making.
AB  - PURPOSE: The purpose of this paper is to provide an overview of the
      organisational and procedural arrangements for priority setting in England and
      Wales. It describes the role of social values in the decision-making process.
      DESIGN/METHODOLOGY/APPROACH: The processes and content of decisions made by the
      National Institute for Health and Clinical Excellence are analysed using the
      framework developed by Clark and Weale for identifying social values in health
      priority-setting. FINDINGS: While countries are seeking to achieve similar
      outcomes from their health prioritisation processes, each country has established
      different systems that reflect the social and legal framework underpinning their
      health systems. England is somewhat unique in being explicit about assessing
      "value for money" and using formal cost-effectiveness in developing policy.
      ORIGINALITY/VALUE: Many countries are now considering the use of formal health
      economic methodologies to assess the value and prioritise health care
      interventions. However there is increasing recognition of the importance of
      values other than efficiency (cost effectiveness) in making acceptable decisions.
      This is manifest in the range of potential new approaches being developed
      including multiple criteria decision analysis.

PMID- 22852459
TI  - Social values and health priority setting in Germany.
AB  - PURPOSE: The purpose of this paper is to provide an overview of health priority
      setting structures in Germany. It reflects on how and which social values may
      influence decision making, and in particular investigates the role of the
      Institute for Quality and Efficiency in Health Care (IQWiG) in integrating
      evidence-based decision making into the German system.
      DESIGN/METHODOLOGY/APPROACH: The paper applies Clark and Weale's framework of
      analysis for Social Values and Health Priority Setting to the German context.
      Placing German health care decision making into Clark and Weale's framework
      allows for an analysis of the role and content of social values in different
      dimensions of decision making. FINDINGS: Germany has witnessed significant
      changes in its health care decision-making procedures in recent decades. The
      establishment of the Institute of Quality and Efficiency in Health Care (IQWiG)
      represents an effort to introduce health technology assessment (HTA) as a formal
      element of decision making in health care. In doing so, Germany has made unique
      methodological and structural choices that reflect the social values and
      institutional traditions that underpin its self-governing statutory health
      insurance (SHI) system. The empirical evidence suggests that the principle of
      solidarity is upheld as a core value in health priority setting in Germany.
      ORIGINALITY/VALUE: The German case of health priority setting highlights some of
      the challenges involved when introducing centralised HTA structures to a self
      governing SHI system. As such, this paper contributes to an understanding of the
      different forms that HTA can take, what social values they embody and how they
      can affect health priority setting in different ways.

PMID- 22852460
TI  - Consideration of social values in the establishment of accountable care
      organizations in the USA.
AB  - PURPOSE: The purpose of this paper is to introduce the new US health
      organizations called accountable care organizations (ACOs) which are expected to
      improve the quality and reduce the cost of healthcare for Medicare enrolees. It
      assesses the importance of ACOs, defining and articulating the values that will
      underpin their strategic and clinical decision making.
      DESIGN/METHODOLOGY/APPROACH: This paper uses a social values framework developed
      by Clark and Weale to consider the values relevant to ACOs. FINDINGS: It is
      likely that social values could be made more explicit in a US setting than they
      have ever been before, via the new ACOs. Social values could start to form part
      of a local health economy's marketing strategy. ORIGINALITY/VALUE: ACOs are very
      new. This paper identifies that they will need to be very explicit about the
      values relevant to them. The development of ACOs and the articulation of social
      values therein may even form the basis of a meaningful dialogue on the importance
      of assessing value for money or cost-effectiveness in the wider US health policy
      environment.

PMID- 22852461
TI  - Universal health coverage and litigation in Latin America.
AB  - PURPOSE: Over the last five years many middle-income Latin American countries
      have seen a steep increase in the number of cases litigating access to curative
      services. The purpose of this paper is to explore this complex phenomenon and
      outline some of its roots and impacts. DESIGN/METHODOLOGY/APPROACH: The authors
      use an interdisciplinary approach based on a literature review and workshops
      convened to discuss the issue. FINDINGS: A range of reasons can explain this
      increased legal activity. These include: a renewed judicial approach to the
      enforcement of the right to health; a more demanding public interest; an
      increased prevalence of non communicable diseases; and limited capacity for fair
      benefit package. ORIGINALITY/VALUE: The findings in this paper argue for the need
      to incorporate a rights-based approach to health policy as a foundation of
      societal efforts to achieve universal health coverage in Latin America.

PMID- 22852462
TI  - A proposal for a new social values research program and policy network.
AB  - PURPOSE: The purpose of this paper is to demonstrate that the social values
      framework developed by Clark and Weale could be applied to publicly available
      data and to explore the concordance between the framework values and those
      present in the statements of decision-making protocols of Health Technology
      Assessment Agencies. DESIGN/METHODOLOGY/APPROACH: The web sites of the National
      Institute for Health and Clinical Excellence (NICE); the All Wales Strategy
      Medicines Group; and the Scottish Medicines Consortium were searched for
      references to social value statements and assessed according to the social values
      framework. FINDINGS: The framework was easy to apply and demonstrated that it is
      possible to find statements of operational expression of a range of social values
      in the description of the decision protocols used by the public agencies. Most of
      the framework's values find some expression in the statements of the decision
      protocols, but there are differences. For example, the All Wales Group, when
      discussing clinical effectiveness, explicitly refers to an assessment via
      "pathways of care" in a way that neither of the other two do. The value of
      autonomy is explicitly mentioned by NICE but not by the other two, whereas the
      value of solidarity (a value most typically associated with European social
      insurance systems) finds only indirect expression in the guidance notes of all.
      PRACTICAL IMPLICATIONS: The paper provides further information that will be
      useful in revising the framework in preparation for its role in future data
      collection. ORIGINALITY/VALUE: This is the initial step in developing a social
      values instrument that will support health policy decisions. While there are
      other check lists of social values, this is the first time that an approach to
      creating a framework is being tested empirically.

PMID- 22852463
TI  - PDMS-gold nanocomposite platforms with enhanced sensing properties.
AB  - Gold-poly(dimethyl siloxoxane) (Au-PDMS) nanocomposite films with a high
      elasticity were fabricated for sensing experiments. The nanocomposite was
      prepared by a novel in-situ method by using the ethanol solution of the
      chloroauric acid. The high rate of permeation of ethanol in the polymer film,
      compared to an aqueous solution, allows the introduction of the gold precursor
      into the polymer network with a higher rate and, thus the reduction reaction is
      accelerated. The strong hydrophobicity of the as-prepared films precludes the
      diffusion of aqueous solutions of biomolecules in the polymer network, essential
      for sensing purposes. In order to modify the morphology and the surface
      properties of the samples, they have been heat-treated and the polymer network
      has been expanded mechanically by repeated swellings and shrinkages. As a result,
      the free volume of the polymer is increased substantially and thus, the
      biosensing capability of the material is improved. The effect of gold
      nanoparticles on the porosity and the mechanical properties of the material has
      been studied. The highest value of the sensitivity (around 70 nm/RIU) has been
      obtained for the samples that were annealed and, subsequently swollen in toluene.
      Biosensing experiments involving antigen-antibody interactions showed a high
      sensitivity. The results of this work are relevant for sensing in a microfluidic
      environment.

PMID- 22852464
TI  - Inclusion of water insoluble drugs in amorphous silica nanoparticles.
AB  - Amorphous silica nanoparticles (a-SiNPs) with high surface area and small pore
      size have been synthesized using a zwitterionic surfactant in acid media. The
      produced nanoparticles displayed large specific surface area (-850 m2/g) with an
      average particles size of 45 nm. The loading efficiency was assessed by
      incorporating three model water insoluble active substances Carbamazepine (CBZ),
      Ibuprofen (IBU) and Cyclosporin (CyA) via passive loading and it was found to
      varying from 15-40%. The loaded silica nanoparticles were analyzed using X-ray
      powder diffraction (XRPD) and differential scanning calorimetry (DSC) to
      investigate the state of the adsorbed active agents. CyA was found to be in
      amorphous state, IBU was partially crystalline while CBZ was transformed into
      form I. The dissolution profiles showed rapid release for CBZ while IBU and CyA
      demonstrated prolonged release for 24 hr. The viability of Caco-2 cells was not
      affected in the presence of a-SiNPs showing negligible cytotoxicity (85%) at high
      concentrations up to 15 mg/ml.

PMID- 22852465
TI  - Novel copper (Cu) loaded core-shell silica nanoparticles with improved Cu
      bioavailability: synthesis, characterization and study of antibacterial
      properties.
AB  - We report synthesis of a novel core-shell silica based antimicrobial
      nanoparticles where the silica shell has been engineered to accommodate copper
      (Cu). Synthesis of the core-shell Cu-silica nanoparticle (C-S CuSiO2NP) involves
      preparation of base-hydrolyzed Stober silica "seed" particles first, followed by
      the acid-catalyzed seeded growth of the Cu-silica shell layer around the core.
      The Scanning Electron Microscopy (SEM) and the Transmission Electron Microscopy
      (TEM) measured the seed particle size to be -380 nm and the shell thickness to be
      -35 nm. The SEM particle characterization confirms formation of highly
      monodispersed particles with smooth surface morphology. Characterization of
      particle size distribution in solution by Dynamic Light Scattering (DLS)
      technique was fairly consistent with the electron microscopy results. Loading of
      Cu to nanoparticles was confirmed by the SEM-Energy Dispersive X-Ray Spectroscopy
      (EDS) and Atomic Absorption Spectroscopy (AAS). The Cu loading was estimated to
      be 0.098 microg of metallic copper per mg of C-S CuSiO2NP material by the AAS
      technique. Antibacterial efficacy of C-S CuSiO2NP was evaluated against E. coli
      and B. subtilis using Cu hydroxide ("Insoluble" Cu compound, sub-micron size
      particles) as positive control and silica "seed" particles (without Cu loading)
      as negative control. Bacterial growth in solution was measured against different
      concentrations of C-S CuSiO2NP to determine the Minimum Inhibitory Concentration
      (MIC) value. The estimated MIC values were 2.4 microg metallic Cu/mL for both E.
      coli and B. subtilis. Bac-light fluorescence microscopy based assay was used to
      count relative population of the live and dead bacteria cells. Antibacterial
      study clearly shows that C-S CuSiO2NP is more effective than insoluble Cu
      hydroxide particles at equivalent metallic Cu concentration, suggesting
      improvement of Cu bioavailability (i.e., more soluble Cu) in C-SCuSiO2NP material
      due to its core-shell design.

PMID- 22852466
TI  - Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes
      in cancer treatment.
AB  - Several functionalized carbon nanotubes have been designed and tested for the
      purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for
      siRNA deliverey were investigated delivery in parallel with an efficient
      commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53
      siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection
      agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of
      gene inhibition was observed in the cases treated with p53 siRNA gene; in the
      case of transfection with siPort, the NeoFX value was 33.8%, while in the case of
      SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing
      capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX
      delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH
      delivery system. SWNTC-COOH we have been showed to have to be an efficient
      carrier system. The results from the inhibition of gene expresion for both
      transfection systems were confirmed at protein level. Overall, the lowest mRNA
      expression was confirmed at protein level, especially in the case of p53 siRNA
      and TNF-alpha siRNA transfection. Less efficient reduction protein expressions
      were observed in the case of VEGF siRNA, for both transfection systems at 24 h;
      only at 48 h, there was a statistically significant reduction of VEGF protein
      expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH,
      combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA
      can be used for the efficient delivery of siRNA.

PMID- 22852467
TI  - Preliminary evaluation of a 99mTc labeled hybrid nanoparticle bearing a cobalt
      ferrite core: in vivo biodistribution.
AB  - Magnetic nanoparticles have become important tools for imaging a wide range of
      diseases, improving drug delivery and applying hyperthermic treatment. Iron oxide
      based nanoparticles have been widely examined, unlike cobalt ferrite based ones.
      Herein, monodisperse and stable CoFe2O4 nanoparticles have been produced, coated
      and further stabilized using ethyl 12-(hydroxyamino)-12-oxododecanoate,
      poly(lactic-co-glycolic acid) and bovine serum albumin. The final product, NBRh1,
      was fully characterized and has been directly radiolabeled with 99mTc using SnCl1
      as the reducing agent in high yields. In vitro stability and hyperthermic
      properties of 99mTC-NBRh1 were encouraging for further application in low
      frequencies hyperthermia and biomagnetic applications. In vivo evaluation
      followed after injection in healthy mice. The planar and SPECT imaging data as
      well as the biodistribution results were in accordance, showing high liver and
      spleen uptake as expected starting almost immediately after administration. In
      conclusion the preliminary results for nanoparticles bearing a cobalt ferrite
      core justify further investigations towards potential hyperthermic applications,
      drug transportation and liver or spleen imaging.

PMID- 22852468
TI  - Biosynthesis of gold nanoparticles using catclaw buttercup (Radix Ranunculi
      Ternati) and evaluation of its colloidal stability.
AB  - The biosynthesis of gold nanoparticles using catclaw buttercup (Radix Ranunculi
      Ternati) and their stability have been reported in this paper. The aqueous
      catclaw buttercup was used as mild reducing agent for gold nanoparticles
      synthesis from HAuCl4 solutions. The influence of reaction time, temperature and
      mass ratio of HAuCl4/catclaw buttercup were evaluated to investigate their
      effects on gold nanoparticles synthesis. Under the optimized reaction parameters,
      the gold nanoparticles obtained are characterized by UV-vis spectrum, X-ray
      diffraction (XRD), EDAX technique (EDX), high resolution transmission electron
      microscopy (HRTEM), FTIR spectrum, anthrone-sulfuric colorimetric method, and
      plus Improved-Lowry Protein Assay Kit. The HRTEM images showed that the
      biosynthesized gold nanoparticles are mostly spherical with size range from 9-24
      nm. Furthermore, it was found that the biosynthesized gold nanoparticles
      possessed outstanding colloid stability in aqueous solutions as a function of
      category and concentration of monovalent salt and pH value of the solution when
      compared with chemosynthetic ones with the similar size. Anthrone-sulfuric
      colorimetric method revealed that there is no sugar in the biosynthesized gold
      colloid. While Improved-Lowry tests results demonstrated that the existence of
      much protein in the biosynthesized gold colloid, which may played an important
      role in stabilization of it. Owing to their stability, biocompatibility, lower
      cost and so on, gold nanoparticles synthesized by this biosynthesis method show
      potential application prospect in optoelectronic and biomedicine.

PMID- 22852469
TI  - Cell tolerability and biodistribution in mice of indocyanine green-loaded lipid
      nanoparticles.
AB  - Considering toxicity requirements for clinical translation of fluorescence
      imaging applications, the use of biocompatible carriers for designing near
      infrared emitting contrast agents appears as an attractive alternative to
      semiconductor nanocrystals. Lipid nanoparticles (LNP) have been designed to serve
      as carriers for indocyanine green (ICG), the presently only human-use approved
      near infrared dye. The cytotoxicity and hemocompatibility of these nanoparticle
      based probes are determined in vitro, respectively in mouse 3T3 fibroblasts and
      human blood samples. Comparative biodistribution of free ICG and ICG-LNP in mice
      is monitored, and an ex vivo fluorescence organ quantification is performed
      considering large animal cohorts. Good tolerability and very low hemolytic
      activity are demonstrated for naked and ICG-loaded LNP. Interestingly, ICG-LNP
      lead to long-term plasma fluorescence (> 24 hours) but also a partial intestinal
      reabsorption of ICG between 5 and 24 hours after injection. This novel ICG
      nanoformulation is foreseen to expand rapidly the field of clinical fluorescence
      imaging applications.

PMID- 22852470
TI  - Hydroxyapatites and europium(III) doped hydroxyapatites as a carrier of silver
      nanoparticles and their antimicrobial activity.
AB  - Hydroxyapatites (Ca10(PO4)6(OH)2 and Eu3+:Ca10(PO4)6(OH)2) were synthesized by
      aqueous synthesis route. Hydroxyapatites were impregnated with silver ions that
      were subsequently reduced. XRD, TEM, and SAED measurements were used in order to
      determine the crystal structure and morphology of the final products. The results
      showed the well crystallized hydroxyapatite grains with diameter of about 35 nm
      and with silver nanoparticles on their surface. The antimicrobial activity of the
      nanoparticles against: Staphylococcus aureus ATCC 6538 as model of the Gram
      positive bacteria, Escherichia coli ATCC 11229, and Klebsiella pneumoniae ATCC
      4352 as model of Gram-negative bacteria, were shown with the best activity
      against K. pneumoniae. These nanocomposite powders can be a promising
      antimicrobial agent and a fluorescent material for biodetection due to their
      optical and bioactive properties.

PMID- 22852471
TI  - Elastic vesicles for transdermal drug delivery of hydrophilic drugs: a comparison
      of important physicochemical characteristics of different vesicle types.
AB  - The aim of this study is to evaluate the influence of different lipid vesicular
      systems on the skin permeation ability of hydrophilic molecules, and understand
      if and which vesicle physicochemical properties may be used as predictive tools.
      Calcein and carboxyfluorescein were used as hydrophilic drug models. All vesicles
      (conventional liposomes [CLs], transfersomes [TRs] and invasomes [INVs]), were
      characterized for particle size distribution, zeta-potential, vesicular shape and
      morphology, encapsulation efficiency, integrity, colloidal stability, elasticity
      and finally in vitro human skin permeation. Dynamic light scattering (DLS) and
      cryo-transmission electron microscopy (cryo-TEM) defined that almost all vesicles
      had spherical structure, low polydispersity (PI < 0.2) and nanosize. Elasticity
      values (measured by extrusion through membranes) were in the order INVs > TRs >
      CLs. Three vesicle types were selected (having different elasticity) and in vitro
      skin permeation experiments demonstrated that calcein permeation was minimal from
      an aqueous solution, slightly enhanced from CLs, and enhanced by 1.8 and 7.2
      times from TRs and INVs, respectively. Permeation and elasticity values were
      correlated by rank order but not linearly, indicating that elasticity can be used
      as a crude predictive tool for enhancement of skin transport. Drug encapsulation
      efficiency was not found to be an important factor in the current study.

PMID- 22852472
TI  - Targeted thrombolysis by using of magnetic mesoporous silica nanoparticles.
AB  - Thrombolytics inevitably led to the risk of hemorrhagic complications due to
      their non-specific plasminogen activation in treatment of thrombosis. The aim of
      this study was to determine whether a kind of superparamagnetic mesoporous silica
      nanoparticle with expanded pore size could achieve effectively targeted
      thrombolysis. The magnetic mesoporous silica nanoparticles (M-MSNs) with the pore
      size of 6 nm were prepared by method of the surfactant templating on nano
      magnetic particles. We investigated the feasibility and efficacy of target
      thrombolysis with the resultant spheres through fibrin agarose plate assay (FAPA)
      and a dynamic flow system in vitro. It displayed a 30-fold enhancement of
      urokinase (UK) loading capacity over the particles without mesoporous layer or
      the magnetic spheres with mesopores of 3.7 nm. A sustained release behavior was
      observed due to its larger pore size, higher surface area and narrow mesopore
      channals contrast to non-mesoporous and small mesopore of 3.7 nm controls.
      Meanwhile, fibrin agarose plate assay revealed that UK/M-MSNs exhibited a more
      rapid growth rate of thrombolysis even lasting for 3 days. Additionally, flow
      model test in vitro suggested this kind of nanoparticle complex enhanced the
      thrombolysis efficacy by 3.5 fold over the same amount of native UK in 30 min.
      When compared to non-mesoporous and small mesopore controls, it also represented
      an extremely higher lysis efficiency (ANOVA, P < 0.01) and a shorter reperfusion
      time (ANOVA, P < 0.001). Such a magnetic mesoporous silica nanoparticle carrier
      was expected to be further studied for targeted thrombolytic therapy.

PMID- 22852473
TI  - Enhancement of cisplatin sensitivity in lung cancer xenografts by liposome
      mediated delivery of the plasmid expressing small hairpin RNA targeting Survivin.
AB  - Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is
      abundantly expressed in a variety of cancer cells, including lung cancer cells,
      resulting in low sensitivity of these cells to various apoptotic stimuli;
      Cisplatin (CDDP), a commonly used chemotherapeutic agent of several cancers, has
      a major limitation because of its toxicity at high concentration. In the present
      study, we constructed a plasmid encoding Survivin shRNA to knockdown survivin
      with low dose DDP both in vitro and in vivo. The specificity and potency of the
      shRNA were validated by western blot, flow cytometric and MTT in H292 lung
      cancers cells. In vivo, therapy experiments were conducted on nude mice bearing
      H292 xenograft tumors. The Survivin shRNA expression plasmid was administered
      systemically in combination with low-dose CDDP on a frequent basis. Assessments
      of angiogenesis, cell proliferation and apoptosis were performed by using
      immunohistochemistry against CD31, Ki67 and TUNEL assays, respectively. The
      results revealed that treatment with the Survivin shRNA plus low-dose CDDP
      reduced volume by approximately 83.13% compared with the blank control (P <
      0.01), accompanied with angiogenesis inhibition (p < 0.01), tumor cell
      proliferation suppression (p < 0.05) and apoptosis induction (p < 0.01).
      Moreover, combination treatment also significantly reduced the mean tumor volume
      compared with other treatment alone (p < 0.05). Taken together, our study
      suggested that silencing of survivin sensitized H292 lung cancer cells to
      chemotherapy of CDDP, suggesting potential applications of the combined approach
      in the treatment of lung cancer.

PMID- 22852474
TI  - Titania nanotube arrays as interfaces for blood-contacting implantable devices: a
      study evaluating the nanotopography-associated activation and expression of blood
      plasma components.
AB  - The constant exposure of implantable biomaterials such as titanium and titanium
      alloys to blood-introducesserious and ongoing concerns regarding poor blood
      material interactions. To date, all blood-contacting materials have been shown to
      initiate immunological events in the form of inflammation, thrombosis, fibrosis
      and infection; potentially leading to complete implant failure. Material surfaces
      that provide biomimetic cues such as nanoscale architectures have been shown to
      elicit improved cellular interaction; and thus, may provide possible solutions
      for enhancing blood-compatibility. However, limited information exists about the
      thrombogenicityof nanoscalesurface architectures. In this study, we have
      evaluated the efficacy of titania nanotube arrays as interfaces for blood
      contacting devices by investigating the thrombogenic effects using whole blood
      plasma. Thus, platelet/leukocyte adhesion, activation and interaction,
      morphology, complement activation, contact activation, platelet release reaction,
      fibrinogen expression and material cytotoxicity were evaluated to determine the
      in vitro thrombogenicity. The results presented here indicate a decrease in
      thrombogenic effects of titania nanotube arrays as compared to biomedical grade
      titanium after 2 hours of contact with whole blood plasma. This work shows the
      improved blood-compatibility of titania nanotube arrays, identifying this
      specific nanoarchitecture as a potentially optimal interface for promoting the
      long-term success of blood contacting biomaterials.

PMID- 22852475
TI  - In vivo evaluation of curcumin loaded nanosuspensions by oral administration.
AB  - The current study was aimed at preparing the curcumin nanosuspension (CUR-NS) to
      improve the solubility and oral absorption of CUR. Prepared from a tandem of
      ultra-turrax homogenization and high pressure homogenization, the CUR-NS showed
      spherical shape under transmission electron microscopy with an average diameter
      of 210.2 nm. The absorption of CUR-NS in the gastrointestinal (GI) tract was
      studied in rats using an in situ single pass perfusion method. It was found that
      the absorption percentage in stomach was 9.20% within 2 h. The absorption process
      in intestine was first-process with passive diffusion mechanism, and the main
      absorptive segments were proven to be in the duodenum and jejunum. A
      pharmacokinetic study was conducted in mice after oral administration of CUR at
      250 mg/kg in the form of either CUR-NS or CUR suspension. The plasma
      concentration-time curves were both fitted to a one-compartment model and the
      relative bioavailability of CUR-NS to CUR suspension was 680.03%. The effects of
      CUR-NS on the structural properties of the intestinal mucosal membrane of rats
      were investigated by fluorescence polarization and circular dichroism in vitro.
      After treatment with CUR-NS, not only the fluidity of intestinal mucosal membrane
      increased but also the conformation of the membrane protein loosed, which
      increased the gastrointestinal absorption of CUR-NS. These studies provided the
      evidence that NS was valuable as an oral delivery carrier to enhance the
      absorption of CUR.

PMID- 22852476
TI  - Regulation of c-Myc and Bcl-2 induced apoptosis of human bronchial epithelial
      cells by zinc oxide nanoparticles.
AB  - Zinc oxide nanoparticles (ZnO NPs) are increasingly recognized for their
      cytotoxicity, whereas little is known about the toxicity mechanisms of ZnO NPs in
      human cells. To explore the possible molecular mechanisms for apoptosis induced
      by ZnO NPs, we investigated the relevant apoptotic signaling in human bronchial
      epithelial (16HBE) cells. ZnO NPs were found to induce intracellular reactive
      oxygen species (ROS) generation accompanied with the mitochondrial membrane
      potential (MMP, deltapsi(m)) reduction in 16HBE cells. Further, the expressions
      of two key apoptotic trigger regulators were determined by quantitative real time
      PCR and Western blot analysis. It demonstrated that following the exposure of
      16HBE cells to ZnO NPs, both levels of mRNA and protein expression of c-Myc were
      significantly up-regulated, whereas the expressions of Bcl-2 mRNA and protein
      were down-regulated. Our results suggested that apoptosis induced by ZnO NPs
      might primarily involve the regulations of c-Myc and Bcl-2 gene expressions
      besides decline of MMP in 16HBE cells.

PMID- 22852477
TI  - Stimulation of minerals by carbon nanotube grafted glucosamine in mouse
      mesenchymal stem cells for bone tissue engineering.
AB  - In the recent years, Single Walled Carbon Nanotube (SWCNT) is known to play a
      vital role in preparation of artificial bone materials. For this, we have
      prepared certain complexes of SWCNT grafted with different molecular weight
      polysaccharides, named as SWCNT-Glucosamine, SWCNT-Chitooligosaccharide (< 1
      KDa), SWCNT-Chitooligosaccharide (1-3 KDa), SWCNT-Chitosan (310 KDa) and SWCNT
      Chitosan (510 KDa) and subjected to bone tissue engineering application in vitro
      with mesenchymal stem cells. The physicochemical characteristic results revealed
      the existence of covalent bond between SWCNT and their respective
      polysaccharides. SWCNT-Glucosamine has been used for the cell culture experiment
      due to its highly soluble nature. As compared to glucosamine alone, no cytotoxic
      effect, higher alkaline phosphatase activity and enhanced mineralization have
      been observed in SWCNT-glucosamine. We propose that SWCNT-Polysaccharide
      derivatives are promising biomaterials for bone tissue engineering.

PMID- 22852478
TI  - Nanoplexes for cell imaging and hyperthermia: in vitro studies.
AB  - Novel IR820-polyethylene glycol-diamine nanoplexes (IR820-PDNCs) have potential
      multifunctional imaging-hyperthermia applications in cancer. Nanoplexes were
      formulated by ionic interaction and characterized in vitro for their imaging and
      hyperthermia capabilities. The resulting nanoplexes were approximately 50 nm
      diameter, with a zeta potential of 2.0 +/- 0.9 mV, and able to generate heat upon
      exposure to 808 nm laser. Cytotoxicity studies in SKOV-3, MES-SA and Dx5 cancer
      cell lines demonstrate comparable cytotoxicity of IR820-PDNCs versus free IR820
      after 24 hours. The nanoplexes are able to produce hyperthermic cell growth
      inhibition in all three cancer cell lines after excitation with laser. The level
      of cell growth inhibition caused by hyperthermia is significantly higher for
      IR820-PDNCs compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope
      images after 2.5-hour exposure to 5 microM IR820-PDNCs or 5 microM free IR820
      show increased uptake for IR820-PDNCs compared to free IR820, especially for SKOV
      3 and Dx5 cancer cells. This formulation can potentially be used in
      multifunctional cancer theranostics.

PMID- 22852479
TI  - Evaluating the potential of polyester nanoparticles for per oral delivery of
      amphotericin B in treating visceral leishmaniasis.
AB  - Leishmaniasis is a protozoan disease, which is responsible for response for major
      epidemics in many parts of the World. Amphotericin B (AMB) is one of the drugs
      used to treat leishmaniasis but it must be given intravenously and serious side
      effects such as nephrotoxicity can limit its use. Development of a formulation of
      AMB, which can be given by a non-invasive route but is still as effective as the
      conventional formulation, whilst causing minimal adverse side effects, is
      required. The present study describes a method for scale up production of a per
      oral nanoparticle formulation of AMB (AMB-NP) and compared its efficacy both in
      vitro and in vivo against Leishmania donovavni. Prophylactic studies showed that
      the AMB-NP formulation was significantly more effective (p < 0.05) than the same
      dose of AMB solution at suppressing parasite numbers compared to controls in bone
      marrow derived macrophages infected with L. donovani. Per oral treatment with AMB
      NP resulted in a significant reduction in liver parasite burdens (p < 0.05)
      compared to control values and the formulation had a similar antileishmanial
      activity against parasites with different inherent susceptibilities to sodium
      stibogluconate.

PMID- 22852481
TI  - Radiation risk. Why you should think twice before getting a CT scan.

PMID- 22852480
TI  - Comparison of pharmacokinetic profiles of PM02734 loaded lipid nanoparticles and
      cyclodextrins: in vitro and in vivo characterization.
AB  - PM02734 is a chemically synthesized depsipeptide derived from the marine
      kahalalides family with a broad spectrum of activity against solid tumors in
      vitro and in vivo, but presenting low bioavailability. In this work, solid lipid
      nanoparticles made of Precirol ATO 5 have been developed using a hot
      homogenization method followed by high shear homogenization and ultrasonication.
      These solid lipid nanoparticles show suitable size (around 150 nm) and
      encapsulation efficiency (nearly 70%) for the oral administration of the compound
      PM02734. A physical-chemical stability study was performed after 6 months of
      storage at different thermical conditions, concluding that solid lipid
      nanoparticles stored at 4 degrees C were more stable than solid lipid
      nanoparticles stored at 25 degrees C. The pharmacokinetic profile of drug-loaded
      solid lipid nanoparticles was also evaluated in Beagle dogs and compared with
      that of a cyclodextrin-based delivery system by means of AUC, C(max) and T(max)
      parameter estimation. Solid lipid nanoparticle based formulation provided a
      sustained release of the drug for a longer period of time than the cyclodextrins.

PMID- 22852482
TI  - More U.S. soldiers have killed themselves than have died in the Afghan war. Why
      can't the Army win the war on suicide?

PMID- 22852483
TI  - The fast-food ethicist.

PMID- 22852484
TI  - Assessing the impact of a wood stove replacement program on air quality and
      children's health.
AB  - Many rural mountain valley communities experience elevated ambient levels of fine
      particulate matter (PM*) in the winter, because of contributions from residential
      wood-burning appliances and sustained temperature inversion periods during the
      cold season. A wood stove change-out program was implemented in a community
      heavily affected by wood-smoke-derived PM2.5 (PM < or = 2.5 microm in aerodynamic
      diameter). The objectives of this study were to evaluate the impact of this
      intervention program on ambient and indoor PM2.5 concentrations and to identify
      possible corresponding changes in the frequency of childhood respiratory symptoms
      and infections and illness-related school absences. Over 1100 old wood stoves
      were replaced with new EPA-certified wood stoves or other heating sources.
      Ambient PM2.5 concentrations were 30% lower in the winter after the changeout
      program, compared with baseline winters, which brought the community's ambient
      air within the PM2.5 standards of the U.S. Environmental Protection Agency (U.S.
      EPA). The installation of a new wood stove resulted in an overall reduction in
      indoor PM2.5 concentrations in a small sample of wood-burning homes, but the
      effects were highly variable across homes. Community-level reductions in wood
      smoke-derived PM2.5 concentration were associated with decreased reports of
      childhood wheeze and of other childhood respiratory health conditions. The
      association was not limited to children living in homes with wood stoves nor does
      it appear to be limited to susceptible children (e.g., children with asthma).
      Community-level reductions in wood-smoke-derived PM2.5 concentration were also
      associated with lower illness-related school absences among older children, but
      this finding was not consistent across all age-groups. This community-level
      intervention provided a unique opportunity to prospectively observe exposure and
      outcome changes resulting from a targeted air pollution reduction strategy.

PMID- 22852486
TI  - Bumpy start.
AB  - Providers are flocking to Medicare's ACO program. But many are signing contracts
      on a leap of faith, with no guarantees of improved care or financial benefit. And
      the delay in data for many ACOs is bad news, because their success relies on
      data. "While we have a willingness to share data, it's not always as simple as we
      had hoped," says Marilyn Tavenner, left, of the CMS.

PMID- 22852485
TI  - Allergic inflammation in the human lower respiratory tract affected by exposure
      to diesel exhaust.
AB  - To improve understanding of human health risks from exposure to diesel exhaust
      particles (DEP*), we tested whether immunologic effects previously observed in
      the human nose also occur in the lower airways. Our overall hypothesis was that
      cell influx and production of cytokines, chemokines, immunoglobulin E (IgE), and
      other mediators, which would be measurable in sputum and blood, occur in people
      with asthma after realistic controlled exposures to diesel exhaust (DE). In Phase
      1 we tested for direct effects of DE in subjects with clinically undifferentiated
      mild asthma. In Phase 2 we tested whether DE exposure would exacerbate response
      to inhaled cat allergen in subjects with both asthma and cat sensitivity. The
      exposure facility was a controlled-environment chamber supplied with DE from an
      idling medium-duty truck with ultra-low-sulfur fuel and no catalytic converter.
      We exposed volunteers for 2 hours with intermittent exercise to exhaust with DEP
      mass concentration near 100 microg/m3. Exposures to nitrogen dioxide (NO2) near
      0.35 ppm (similar to its concentration in DE) and to filtered air (FA) served as
      controls. Blood was drawn before exposure on day 1 and again the next morning
      (day 2). Sputum was induced only on day 2. Bronchial reactivity was measured -1
      hour after exposure ended. Supplementary endpoints included measures of blood
      coagulation status, cardiopulmonary physiology, and symptoms. Each phase employed
      15 subjects with asthma; 3 subjects participated in both phases. In Phase 1,
      airway reactivity was measured with inhaled methacholine; in Phase 2, with
      inhaled cat allergen. We found little biologic response to DE exposure compared
      with exposure to control atmospheres. In Phase 1, interleukin 4 (IL-4) in sputum
      showed an estimated 1.7-fold increase attributable to DE exposure, which was
      close to statistical significance; airway resistance increased modestly but
      significantly on day 2 after DE exposure; and nonspecific symptom scores
      increased significantly during DE exposure. In Phase 2, indicators of airway
      inflammation in sputum showed a possibly meaningful response: polymorphonuclear
      leukocytes (PMNs) and eosinophils increased after DE exposure, whereas
      macrophages decreased. IgE in sputum and the bronchoconstrictive response to cat
      allergen varied significantly between atmospheres, but not in patterns consistent
      with our primary hypothesis. Symptom score changes relatable to DE exposure were
      smaller than those in Phase 1 and not statistically significant. Controlled
      exposures, lasting 2 hours with intermittent exercise, to diluted DE at a
      particle mass concentration of 100 microg/m3 did not evoke clear and consistent
      lower-airway or systemic immunologic or inflammatory responses in mildly
      asthmatic subjects, with or without accompanying challenge with cat allergen.
      Likewise, these DE exposures did not significantly increase nonspecific or
      allergen-specific bronchial reactivity. A few isolated statistically significant
      or near-significant changes were observed during and after DE exposure, including
      increases in nonspecific symptoms (e.g., headache, nausea) suggestive of subtle,
      rapid-onset systemic effects. It is possible the lower respiratory tract is more
      resistant than the nose to adjuvant effects of diesel particles on allergic
      inflammation, so that no meaningful effects occur under exposure conditions like
      these. Alternatively, the experimental conditions may have been near a threshold
      for finding effects. That is, important lower respiratory effects may occur but
      may be detectable experimentally with slightly higher DEP concentrations, longer
      exposures, more invasive testing (e.g., bronchoalveolar lavage), or more
      susceptible subjects. However, ethical and practical barriers to such experiments
      are considerable.

PMID- 22852487
TI  - WellPoint's Medicaid bet.

PMID- 22852488
TI  - Search on for new ACHE head.

PMID- 22852489
TI  - Chance for change. FTC to target monopolies in court.

PMID- 22852490
TI  - We all pay the tax. Real policy debate should focus on the high cost of the
      uninsured.

PMID- 22852491
TI  - Market pricing. Competition for many specialists continues to drive physician
      salaries higher, annual survey shows.

PMID- 22852492
TI  - Learning from experience. 5010 process offers lessons in communication: experts.

PMID- 22852493
TI  - [Improving patient care through coordination of care].

PMID- 22852494
TI  - [The nurse coordinator in nursing homes].
AB  - The role of the nurse coordinator in nursing homes is not always well defined.
      Their missions vary depending on the context and in particular on the doctor
      coordinator's missions. Recognition of the skills involved is nevertheless
      necessary for the caregivers who provide high-quality care.

PMID- 22852495
TI  - [Therapeutic bath and Alzheimer's disease].
AB  - To safeguard the quality of life of people suffering from Alzheimer's by the
      creation of an individual care plan, by identifying pleasurable activities or
      fond memories of the individual, thereby restoring a sense of present well being.
      The therapeutic bath, an action which might be considered somewhat
      straightforward, in fact enables the measurement of the capability of an elderly
      person to respond to stimulation by medical staff.

PMID- 22852496
TI  - [Language disorders and neurodegenerative pathologies].
AB  - Language disorders in elderly people are not exclusively linked to the vascular
      pathology. There are many degenerative causes and the different clinical
      presentations and progression profiles must be known to clinicians. The detection
      of a language disorder during a "memory consultation" warrants an assessment by a
      speech therapist, in order to adapt the neuropsychological assessment and to
      decide on any complementary investigations.

PMID- 22852497
TI  - [Like the elderly, I am just an amateur musician of old French songs].

PMID- 22852498
TI  - [Relational care and the dementia patient].

PMID- 22852499
TI  - [Lung diseases in the elderly].

PMID- 22852501
TI  - [Chronic respiratory insufficiency and the elderly patient].
AB  - Chronic respiratory failure is a complex entity of varied etiology and physio
      pathological mechanisms. It is mainly characterised by the respiratory system's
      difficulty in ensuring correct aeration at rest, resulting initially in
      insufficient oxygenation of arterial blood. Treatment is adapted to each etiology
      and aims to compensate for respiratory failure and to ensure the oxygenation of
      the organism.

PMID- 22852500
TI  - [Lung cancer in the elderly: diagnostic and treatment specifics].
AB  - The diagnosis and treatment of elderly patients with lung cancer must take into
      account a number of specificities. The geriatric assessment is a fundamental
      stage in the initial examination.The treatment of localised forms involves
      surgery, with a slightly higher morbimortality in elderly compared to younger
      patients, resulting in the need for a rigorous selection of patients. Advanced
      forms are treated with chemotherapy or targeted therapies, treatment which is
      adapted to the patient and the tumour.

PMID- 22852502
TI  - [Pneumonia in the elderly].
AB  - Pneumonia is a serious medical pathology frequent in elderly people. The
      physiological changes of the respiratory system linked with age reduce postural
      drainage capacities and increase the risk of acute respiratory failure.
      Associated with other comorbidities, chronic inhalation is a major risk factor of
      pneumonia in elderly people. Prevention is based on vaccination, nutrition,
      dental care and an adapted diet.

PMID- 22852503
TI  - [Tuberculosis in the elderly].
AB  - For people born in France, age is a major risk factor for developing
      tuberculosis.This curable pathology still has a high mortality rate which
      increases with age. Diagnosis difficulties, tolerance and compliance with
      treatment are issues specific to old age. An active policy of prevention,
      monitoring and training should enable the incidence of this pathology to continue
      to fall.

PMID- 22852504
TI  - [Chest congestion and respiratory therapy in the elderly].
AB  - In geriatrics, the usual approach is "primum non nocere":"first do no harm".
      Physiotherapists must adapt the techniques and exercises they use to the clinical
      situation of each patient. Close collaboration with the doctor enables care to be
      modified in accordance with the development of the symptomatology and the
      therapeutic objectives.

PMID- 22852506
TI  - [Spinal disorders].

PMID- 22852505
TI  - [Bibliography. Lung diseases].

PMID- 22852507
TI  - Dental Olympians, 2012.

PMID- 22852508
TI  - Greener infection prevention.

PMID- 22852509
TI  - Ethical marketing in'aesthetic' ('esthetic') or'cosmetic dentistry'. Part 1.
AB  - Prior to undertaking any elective,'cosmetic' dental procedures, it is vital for
      the treating dentist to discuss the merits and drawbacks of all viable options.
      It is important that the patient understands what the consequences and
      limitations of treatment are likely to be, and what the potential failures could
      entail later in his/her life. Informed consent should be obtained (preferably in
      writing) and the clinical notes and records should be clearly documented, with
      accurate and concise details provided of all the investigations carried out, and
      their findings, as well as including details of the various discussions that have
      taken place. Dentists need to be aware of the existence of heightened
      expectations in this group of patients and be cautious about accepting patients
      who have unrealistic 'cosmetic' expectations. Where possible, cosmetic or
      aesthetic dental treatment should be provided which is minimally destructive and,
      in the long-term, be in the 'best interests' of the patient. Important matters
      such as the gaining of informed consent and maintaining meticulous,
      contemporaneous dental records will also be emphasized. It is hoped that the
      article will provide clear definitions of some commonly used terms such as
      'ethical marketing', 'ethics', and 'values', which are often used in association
      with the marketing, planning and undertaking of supposedly 'cosmetic' dental
      procedures. The important role of less invasive alternative treatment options
      will also be emphasized. CLINICAL RELEVANCE: The aims of this article are to
      consider the common pitfalls that may arise when contemplating the marketing and
      provision of invasive,'cosmetic, dental restorations and to discuss how best to
      avoid a dento-legal claim where such treatment plans may not fulfil the patient's
      desired outcome.

PMID- 22852510
TI  - Endodontic 'Solutions'. Part 2: An audit comparing current practice in Belfast
      with UK and Republic of Ireland Dental Schools.
AB  - Endodontic lubricants, irrigating solutions and medicaments help reduce the
      microbial load within root canals. Primary and secondary cases involve different
      microbes. Each'solution'or combinations thereof could play a significant role but
      no detailed guidelines exist on their use. An audit was undertaken to compare
      current practice in Belfast Dental School to the others across the UK and
      Republic of Ireland (ROI). This audit highlighted three main differences between
      Belfast and other dental schools. Many other institutions utilized other
      irrigants besides sodium hypochlorite (NaOCl), different intracanal medicaments,
      including calcium hydroxide, and higher concentrations of NaOCl. Having gathered
      this information, we ask, 'Is there sufficient evidence to change the endodontic
      regime currently used at Belfast Dental School?'. Using the findings from the
      literature review (Part 1), we introduce new evidence-based protocols for primary
      and secondary cases for use in Belfast Dental School. CLINICAL RELEVANCE: In the
      absence of detailed clinical guidelines on the use of endodontic lubricants,
      irrigants and medicaments in primary and secondary cases, it is important to be
      aware of current practice in UK and ROI dental schools where dentists and
      specialists are trained.

PMID- 22852511
TI  - Lonizing radiation regulations and the dental practitioner: 3. Quality assurance
      in dental radiography.
AB  - This is the last in a series of three articles on X-ray dose reduction and covers
      aspects of quality assurance. The first outlined radiation physics and protection
      and the second the legislation relating to radiation safety. CLINICAL RELEVANCE:
      Quality assurance is an essential part of dental radiography and is required to
      produce images of a consistently high standard, necessary for accurate diagnosis.

PMID- 22852512
TI  - Laboratory aspects of zirconia restorations.
AB  - Zirconia restorations are now accepted and commonly prescribed in dentistry.
      However, these materials undergo hydrothermal ageing which can reduce their
      clinical performance. Appropriate handling is essential to limit the
      restorations' susceptibility to low temperature degradation/ageing. Through
      appropriate clinical prescribing and laboratory manufacture, an aesthetic, strong
      and long-lasting restoration can be fabricated. CLINICAL RELEVANCE: This article
      will inform the reader about zirconia as a dental material as well as how best to
      handle a zirconia restoration.

PMID- 22852514
TI  - Gingival enlargement and mesiodens associated with generalized aggressive
      periodontitis: a case report.
AB  - This case report describes the management of an 18-year-old female who presented
      with generalized aggressive periodontitis, gingival enlargement and a mesiodens.
      Diagnosis for aggressive periodontitis was determined based on history, clinical
      findings and radiographic examination. Treatment included oral prophylaxis,
      extraction of the mesiodens and elimination of infectious microorganisms, using a
      combination of surgical intervention and antimicrobial therapy with long-term
      maintenance. CLINICAL RELEVANCE: Presence of gingival enlargement in cases of
      aggressive periodontitis may be clinically confusing; hence, the diagnosis should
      always be based on the patient's history as well as the clinical and radiographic
      findings.

PMID- 22852513
TI  - Management of bleeding disorders in the dental practice: managing patients on
      anticoagulants.
AB  - Patients with bleeding disorders pose a challenge for dentists. Most of these
      conditions can be safely treated in the general dental practice. Patients who are
      on anticoagulants represent a large group of bleeding disorders. This article
      reviews the latest evidence in regard to managing those patients. Most of the
      articles reviewed seem to agree on the negligible risk of modification or
      interruption of oral anticoagulants when performing most dental treatments
      because a decreased risk of excessive bleeding might be associated with an
      increased risk of thrombo-embolic complications. However, extensive pre-operative
      assessment is essential to reduce the risk of serious complications. CLINICAL
      RELEVANCE: Patients with bleeding disorders pose a challenge for dentists.
      Adequate understanding of the underlying medical condition is essential to reduce
      the risk of dangerous complications.

PMID- 22852515
TI  - Implant-retained overdentures: a review.
AB  - Implant-retained overdentures represent a treatment option for many patients
      unable to tolerate conventional dentures. They may be specifically indicated in
      patients with altered anatomy, neuromuscular disorders, a pronounced gag reflex
      or severe residual ridge resorption. This article discusses the different ways in
      which implant overdentures can be retained, outlines some of the clinical stages
      involved in planning and providing these prostheses, and highlights long-term
      maintenance requirements associated with implant-retained overdentures. CLINICAL
      RELEVANCE: Patients with implant-retained overdentures are likely to present in
      general dental practice. Practitioners should be aware of issues associated with
      the design, treatment planning and maintenance of these prostheses.

PMID- 22852516
TI  - Oral cancer: comprehending the condition, causes, controversies, control and
      consequences. 17. Osteonecrosis.

PMID- 22852517
TI  - Technique tips--don't throw away the phosphoric acid etch gel, yet!

PMID- 22852518
TI  - Physical signs for the general dental practitioner. Case 95. Onychocryptosis.

PMID- 22852519
TI  - Modern high powered led curing lights and their effect on pulp chamber
      temperature of bulk and incrementally cured composite resin.
AB  - Pulpal temperature changes induced by modern high powered light emitting diodes
      (LEDs) are of concern when used to cure composite resins. This study showed an
      increase in pulp chamber temperature with an increase in power density for all
      light cure units (LCU) when used to bulk cure composite resin. Amongst the three
      LEDs tested, the Elipar Freelight-2 recorded the highest temperature changes.
      Bulk curing recorded a significantly larger rise in pulp chamber temperature
      change than incrementally cured resin for all light types except for the
      Smartligh PS. Both the high powered LED and the conventional curing units can
      generate heat. Though this temperature rise may not be sufficient to cause
      irreversible pulpal damage, it would be safer to incrementally cure resins.

PMID- 22852520
TI  - Provision of resin bonded bridgework for a patient with microstomia secondary to
      scleroderma.
AB  - Scleroderma is a connective tissue disorder that can present with orofacial
      involvement. A 48 year-old patient presented to Cork University Dental Hospital
      with concerns about the appearance of her upper central incisor teeth, which had
      become progressively mobile in recent years. A diagnosis of localised scleroderma
      had been made a number of years previously by her medical practitioner and the
      patient reported that her scleroderma-associated microstomia had progressed
      significantly in recent years. Most reports of this condition advocate the use of
      sectional impression trays and sectional dentures to replace missing teeth. This
      report describes the use of resin-bonded bridgework (RBB) and discusses the
      possible advantages of this treatment option over those already presented in the
      literature.

PMID- 22852521
TI  - Adaptive toothbrush handle: case report of a Thalidomide patient.
AB  - Thalidomide poisoning can result in malformation of limbs, specifically upper
      limbs, compromising manual dexterity. Although Thalidomide has long since been
      withdrawn for use in pregnant patients, its affects on those exposed pose
      significant challenges for patients' oral hygiene maintenance. This case reports
      a novel technique of adaptation to facilitate a Thalidomide poisoned patient in
      maintenance of oral hygiene via an adaptive toothbrush handle.

PMID- 22852522
TI  - Comparison of three anthropometric techniques for tooth selection.
AB  - The absence of a reliable method to assess the proper dimension of artificial
      teeth can lead to errors that reduce aesthetic outcomes of the dental treatment.
      Previous studies indicate facial anthropometric parameters as guides to estimate
      the width of the six maxillary anterior teeth. Nasal width, distance between the
      medialis angles of the eyes and mouth width were measured in young subjects
      Brazilian as well as the width of their six maxillary anterior teeth. Data were
      analyzed by ANOVA/Tukey's (p < or = 0.05). The distance between the medialis
      angles of the eyes is a reliable anthropometric method to indicate the width of
      artificial teeth similar to the natural extracted.

PMID- 22852523
TI  - Antibacterial properties of amalgam and composite resin materials used as cores
      under crowns.
AB  - The Aim of this Study was to compare the bacterial growth in the bulk of both
      amalgam and fluoridated composite resin materials used as cores under crowns at
      core's surface (in the superficial area of the bulk) and depth levels. With 24
      lower premolars, 12 of them were restored with metal posts and amalgam cores
      (group 1). The rest were restored with glass Fiber-reinforced Composite (FRC)
      posts and fluoridated composite resin cores (group 2). All specimens were covered
      with aluminium crowns cemented with resin cement, and then they were soaked in
      natural saliva for three months. Excoriations abraded from the superficial and
      the depth areas of the core materials were cultured under aerobic conditions on
      blood agar plates. After incubation for 2 days, colonies formed on the plates
      were identified, and the CFU mg(-1) counts were recorded accordingly. Statistical
      analysis was performed using an independent sample T test. The mean values of CFU
      mg(-1) counts in group 2 excoriations (surface 39.75, and depth 9.75) were higher
      than the group 1 excoriations (surface 1.67, and depth 0.42). This study supports
      the use of amalgam for building up cores due to its antibacterial properties.
      Composite resin, however, enhanced sizable bacterial growth despite the presence
      of fluoride.

PMID- 22852524
TI  - Self retentive partial silicone auricular prosthesis: a case report.
AB  - An auricular prosthesis may be required for a number of conditions including
      congenital abnormalities, malignancy and trauma, which result in disfigurement of
      the pinna. Whatever the cause of the absence of the pinna, it is a significant
      loss of a prominent part of the face for the person involved. This article
      describes a simple and cost effective technique for retention of a silicone
      partial auricular prosthesis. A Fish-bone shaped substructure (FSS) designed and
      fabricated using orthodontic wire and autopolymerizing acrylic resin, was
      embedded into the silicone elastomer of a self-retentive silicone prosthesis. The
      prosthesis is designed to overcome the disadvantages associated with
      traditionally fabricated prostheses; namely poor structural strength, inadequate
      retention, poor adaptation and durability over time.

PMID- 22852525
TI  - Rehabilitation of an extraoral and intraoral defect complicated with microstomia.
      A study case.
AB  - A 72-year-old man was referred from the surgery department for rehabilitation
      following surgical resection of Basaloid carcinoma. The first surgical
      intervention involved the anterior palatal region and was restored with a simple
      obturator. Two years later further surgery was undertaken to excise a recurrent
      tumor in the nose and part of the cheek. This resulted in an exposed nasal cavity
      and maxillary sinus. In addition, there was a small oral aperture composed of
      thin tissue that stretched to its maximum due to scar formation. The defect was
      restored with a full thickness skin flap but it subsequently broke down leaving
      the midface exposed with limited mouth opening due to tissue contraction and scar
      formation after the flap operation. The defect was rehabilitated with Co-Cr
      obturator intraorally and a silicone nose retained to the naso-palatal extension
      of the obturator by a magnet extraorally. This resulted in practically good
      retention, placement, and adaptation of the two parts of the prosthesis.

PMID- 22852526
TI  - The impact of fractured endodontic file removal on vertical root fracture
      resistance: three-dimensional finite element analysis.
AB  - This study investigated by means of finite element analysis the influence of
      fractured file removal on root fracture resistance in an endodontically-treated
      canine. A 4mm fragment of an endodontic file was deliberately fractured in the
      apical third of an upper canine root and removed by ultrasonic tips. Micro
      computed tomography scans were carried out before and after fractured file
      removal on the same tooth. Two 3D-FE models (before and after file removal) were
      subjected to 100N loading. Results indicate that the fractured file removal
      increased von Mises stresses by 55%. Peak stresses were located around the root
      filling/dentine interface prior to file removal. Following file removal, peak
      stresses were concentrated at the buccal root surface/bone interface that might
      initiate vertical root fracture buccolingually.

PMID- 22852527
TI  - Multidisciplinary treatment approach with one piece implants for congenitally
      missing maxillary lateral incisors: a case report.
AB  - Congenitally missing lateral incisors are a common clinical occurrence. Dental
      Implants have become a primary treatment option for replacement of these teeth.
      Many times in prosthodontic treatment planning a multidisciplinary approach is
      needed for a comprehensive out come. Prosthodontic treatment planning is needed
      prior to the patient's consultation and following treatment acceptance; the
      prosthodontist may need to coordinate treatment needs with other specialists,
      including an orthodontist and an implant surgeon. This article describes
      multidisciplinary management of a case presenting with spaced maxillary anteriors
      due to the congenitally missing lateral incisors. Treatment consisted of initial
      orthodontic space management to obtain adequate space for missing lateral
      incisors. Single piece, narrow diameter implants were placed in edentulous spaces
      on both sides. Aesthetic crown lengthening procedure was performed with all
      anterior teeth along with tissues surrounding the implants. Metal-ceramic crowns
      were given as definitive restorations, resulting into an acceptable aesthetic
      outcome.

PMID- 22852528
TI  - Considering the air quality impacts of bioenergy crop production: a case study
      involving Arundo donax.
AB  - The expanding production of bioenergy crops may impact regional air quality
      through the production of volatile organic compounds such as isoprene. To
      investigate the effects of isoprene-emitting crops on air quality, specifically
      ozone (O(3)) and secondary organic aerosol (SOA) formation, we performed a series
      of model runs using the Weather Research and Forecasting model with Chemistry
      (WRF/Chem) coupled with the Model of Emissions of Gases and Aerosols from Nature
      (MEGAN) simulating a proposed cropland conversion to the giant cane Arundo donax
      for biomass production. Cultivation of A. donax in the relatively clean air of
      northeastern Oregon resulted in an average increase in 8 h O(3) levels of 0.52
      ppb, while SOA was largely unaffected (<+0.01 MUg m(-3)). Conversions in U.S.
      regions with reduced air quality (eastern Texas and northern Illinois) resulted
      in average 8 h O(3) increases of 2.46 and 3.97 ppb, respectively, with daily
      increases up to 15 ppb in the Illinois case, and daytime SOA increases up to 0.57
      MUg m(-3). While cultivation of isoprene-emitting bioenergy crops may be
      appropriate at some scales and in some regions, other areas may experience
      increased O(3) and SOA, highlighting the need to consider isoprene emissions when
      evaluating potential regional impacts of bioenergy crop production.

PMID- 22852529
TI  - Widespread existence of cytosine methylation in yeast DNA measured by gas
      chromatography/mass spectrometry.
AB  - DNA methylation is one of the major epigenetic modifications and has been
      involved in a number of biological processes in mammalian cells. Yeast is widely
      used as a model organism for studying cell metabolism, cell cycle regulation, and
      signal transduction. However, it remains controversial whether methylated
      cytosine (5-methylcytosine, 5mC) exists in the yeast genome. In the current
      study, we developed a highly sensitive method based on gas chromatography/mass
      spectrometry (GC/MS) and systematically examined the incidence of 5mC in 19 yeast
      strains, which represent 16 yeast species. Our results showed that DNA
      methylation is widespread in yeast and the genome-wide DNA methylation of the
      studied yeast strains ranged from 0.014 to 0.364%, which were 1 to 2 orders of
      magnitude lower than that in mammalian cells (i.e., 3-8%). Furthermore, we found
      that the 5mC content in yeast varied considerably at different growth stages and
      DNA methylation inhibitor 5-azacytidine could induce a decrease in genome-wide
      DNA methylation as that in mammalian cells. The demonstration of the universal
      presence of DNA cytosine methylation in yeast constituted the first and essential
      step toward understanding the functions of this methylation in yeast.

PMID- 22852530
TI  - Fingerprinting noncanonical and tertiary RNA structures by differential SHAPE
      reactivity.
AB  - Many RNA structures are composed of simple secondary structure elements linked by
      a few critical tertiary interactions. SHAPE chemistry has made interrogation of
      RNA dynamics at single-nucleotide resolution straightforward. However, de novo
      identification of nucleotides involved in tertiary interactions remains a
      challenge. Here we show that nucleotides that form noncanonical or tertiary
      contacts can be detected by comparing information obtained using two SHAPE
      reagents, N-methylisatoic anhydride (NMIA) and 1-methyl-6-nitroisatoic anhydride
      (1M6). Nucleotides that react preferentially with NMIA exhibit slow local
      nucleotide dynamics and usually adopt the less common C2'-endo ribose
      conformation. Experiments and first-principles calculations show that 1M6 reacts
      preferentially with nucleotides in which one face of the nucleobase allows an
      unhindered stacking interaction with the reagent. Differential SHAPE reactivities
      were used to detect noncanonical and tertiary interactions in four RNAs with
      diverse structures and to identify preformed noncanonical interactions in
      partially folded RNAs. Differential SHAPE reactivity analysis will enable
      experimentally concise, large-scale identification of tertiary structure elements
      and ligand binding sites in complex RNAs and in diverse biological environments.

PMID- 22852531
TI  - Patient advocacy in clinical ethics consultation.
AB  - The question of whether clinical ethics consultants may engage in patient
      advocacy in the course of consultation has not been addressed, but it highlights
      for the field that consultants' allegiances, and the boundaries of appropriate
      professional practice, must be better understood. I consider arguments for and
      against patient advocacy in clinical ethics consultation, which demonstrate that
      patient advocacy is permissible, but not central to the practice of consultation.
      I then offer four recommendations for consultants who engage in patient advocacy,
      and consider the implications of this issue for the field.(1).

PMID- 22852532
TI  - Mediation and advocacy.

PMID- 22852533
TI  - Empowering, teaching, and occasionally advocating: clinical ethics consultants'
      duties to all of the participants in the process.

PMID- 22852534
TI  - Do clinical ethics consultants have a fiduciary responsibility to the patient?

PMID- 22852535
TI  - Clinical ethics consultants: advocates for both patients and clinicians.

PMID- 22852536
TI  - A place for ethics? A place for advocacy?

PMID- 22852537
TI  - Will the last health care professional to forgo patient advocacy please call an
      ethics consult?

PMID- 22852539
TI  - Selecting for disability: acceptable lives, acceptable reasons.

PMID- 22852538
TI  - Physicians' duties and the non-identity problem.
AB  - The non-identity problem arises when an intervention or behavior changes the
      identity of those affected. Delaying pregnancy is an example of such a behavior.
      The problem is whether and in what ways such changes in identity affect moral
      considerations. While a great deal has been written about the non-identity
      problem, relatively little has been written about the implications for physicians
      and how they should understand their duties. We argue that the non-identity
      problem can make a crucial moral difference in some circumstances, and that it
      has some interesting implications for when it is or is not right for a physician
      to refuse to accede to a patient's request. If a physician is asked to provide an
      intervention (identity preserving) that makes a person worse off, then such harm
      provides a good reason for the physician to refuse to provide the intervention.
      However, in cases where different (identity-altering) interventions result in
      different people having a better or worse life, physicians should normally
      respect patient choice.

PMID- 22852540
TI  - Advantageous interventions: will someone be healed?

PMID- 22852541
TI  - The right not to be born: reinterpreting the nonidentity problem.

PMID- 22852542
TI  - A sufficient limit to "reasonable" choices.

PMID- 22852543
TI  - Does the non-identity problem imply a double standard for physicians and
      patients?

PMID- 22852544
TI  - Impersonalism in bioethics.

PMID- 22852547
TI  - Editors' note.

PMID- 22852548
TI  - Advocacy through a prism: a response to commentaries on "patient advocacy in
      clinical ethics consultation".

PMID- 22852550
TI  - Thermoresponsive hydrogel of diblock methylcellulose: formation of ribbonlike
      supramolecular nanostructures by self-assembly.
AB  - This article provides detailed insight into the thermoresponsive gelation
      mechanism of industrially produced methylcellulose (MC), highlighting the
      importance of diblock structure with a hydrophobic sequence of 2,3,6-tri-O-methyl
      glucopyranosyl units for this physicochemical property. We show herein, for the
      first time, that well-defined diblock MC self-assembles thermoresponsively into
      ribbonlike nanostructures in water. A cryogenic transmission electron microscopy
      (cryo-TEM) technique was used to detect the ribbonlike nanostructures formed by
      the diblock copolymers consisting of hydrophilic glucosyl or cellobiosyl and
      hydrophobic 2,3,6-tri-O-methyl-cellulosyl blocks, methyl beta-D-glucopyranosyl-(1
      >4)-2,3,6-tri-O-methyl-celluloside 1 (G-236MC, DP(n) = 10.7, DS = 2.65), and
      methyl beta-D-glucopyranosyl-(1->4)-beta-D-glucopyranosyl-(1->4)-2,3,6-tri-O
      methyl-celluloside 2 (GG-236MC, DP(n) = 28.2, DS = 2.75). Rheological
      measurements revealed that the gel strength of a dispersion of GG-236MC (2, 2.0
      wt %) in water at 70  degrees C was 3.0 times stronger than that of commercial MC
      SM-8000, although the molecular weight of GG-236MC (2) having M(w) = 8 * 10(3)
      g/mol was 50 times smaller than that of SM-8000 having M(w) = 4 * 10(5) g/mol.
      Cryo-TEM observation suggested that the hydrogel formation of the diblock
      copolymers could be attributed to the entanglement of ribbonlike nanostructures
      self-assembled by the diblock copolymers in water. The cryo-TEM micrograph of GG
      236MC (2) at 5  degrees C showed rectangularly shaped nanostructures having a
      thickness from 11 to 24 nm, although G-236MC (1) at 20  degrees C showed no
      distinct self-assembled nanostructures. The ribbonlike nanostructures of GG-236MC
      (2) having a length ranging from 91 to 864 nm and a thickness from 8.5 to 27.1 nm
      were detected above 20  degrees C. Small-angle X-ray scattering measurements
      suggested that the ribbonlike nanostructures of GG-236MC (2) consisted of a
      bilayer structure with a width of ca. 40 nm. It was likely that GG-236MC (2)
      molecules were oriented perpendicularly to the long axis of the ribbonlike
      nanostructure. In addition, wide-angle X-ray scattering measurements revealed
      that GG-236MC (2) in its hydrogel formed the same crystalline regions as 2,3,6
      tri-O-methylcellulose. The influence of the DP of diblock MC with a DS of around
      2.7 on the gelation behavior will be discussed.

PMID- 22852549
TI  - Allylic amination and N-arylation-based domino reactions providing rapid three
      component strategies to fused pyrroles with different substituted patterns.
AB  - New three-component domino reaction providing divergent approaches to
      multifunctionalized fused pyrroles with different substituted patterns have been
      established (40 examples). The direct C(sp(3))-N bond formation was achieved
      through intermolecular allylic amination in a one-pot operation, and N-arylation
      of amines was realized by varying N-amino acid enaminones. The reaction is easy
      to perform simply by mixing three common reactants in acetic acid under microwave
      heating. The reaction proceeds at fast rates and can be finished within 30 min,
      which makes workup convenient to give good chemical yields.

PMID- 22852551
TI  - HIV/AIDS-related stigma felt by people living with HIV from Buea, Cameroon.
AB  - The universal access to treatment and care for people living with HIV (PLWHIV) is
      a major problem especially in Sub-Saharan Africa, where the majority of HIV
      infected people live. However, equally important is the fact that HIV/AIDS
      related stigma is recognized to be a major obstacle to successfully control the
      spread of this disease. In this study we measured the HIV/AIDS-related stigma
      felt by PLWHIV in Cameroon using "The people living with HIV stigma index"
      questionnaire developed by UNAIDS, International Planned Parenthood Federation
      and Global Network of PLWHIV/AIDS among others. A total of 200 questionnaires
      were anonymously administered to PLWHIV in the HIV/AIDS treatment center of the
      Regional Hospital Annex Buea in the South West Region of Cameroon by trained
      academics who were themselves PLWHIV. In this setting the major problems faced by
      the PLWHIV with regard to stigmatization and discrimination were gossiping and
      verbal insults, which was felt by about half of the interviewees. Equally
      important was internal stigma, half of the PLWHIV felt ashamed and guilty to be
      HIV infected. This is the first report of this kind in Cameroon. These results
      will help to better understand HIV/AIDS-related stigma in this setting and in
      turn will improve the quality of life of PLWHIV by promoting their acceptance by
      the community.

PMID- 22852552
TI  - Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and
      sphere cultures.
AB  - BACKGROUND: Aldehyde dehydrogenases belong to a superfamily of detoxifying
      enzymes that protect cells from carcinogenic aldehydes. Of the superfamily,
      ALDH1A1 has gained most attention because current studies have shown that its
      expression is associated with human cancer stem cells. However, ALDH1A1 is only
      one of the 19 human ALDH subfamilies currently known. The purpose of the present
      study was to determine if the expression and activities of other major ALDH
      isozymes are associated with human ovarian cancer and ovarian cancer sphere
      cultures. METHODS: Immunohistochemistry was used to delineate ALDH isozyme
      localization in clinical ovarian tissues. Western Blot analyses were performed on
      lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the
      immunohistochemistry findings. Quantitative reverse transcription-polymerase
      chain reactions were used to measure the mRNA expression levels. The Aldefluor(r)
      assay was used to measure ALDH activity in cancer cells from the four tumor
      subtypes. RESULTS: Immunohistochemical staining showed significant overexpression
      of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal
      ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent,
      as seen from immunohistochemisty, Western blot analysis, and the Aldefluor(r)
      assay. The expression was elevated in the mucinous and endometrioid ovarian
      epithelial tumors than in serous and clear cell tumors. In some serous and most
      clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA
      expression of all studied ALDH isozymes also showed higher expression in
      endometrioid and mucinous tumors than in the serous and clear cell subtypes. The
      expression of ALDH enzymes showed tumor type-dependent induction in ovarian
      cancer cells growing as sphere suspensions in serum-free medium. CONCLUSIONS: The
      results of our study indicate that ALDH enzyme expression and activity may be
      associated with specific cell types in ovarian tumor tissues and vary according
      to cell states. Elucidating the function of the ALDH isozymes in lineage
      differentiation and pathogenesis may have significant implications for ovarian
      cancer pathophysiology.

PMID- 22852554
TI  - A simple AIMD approach to derive atomic charges for condensed phase simulation of
      ionic liquids.
AB  - The atomic charges for two ionic liquids (ILs), 1-n-butyl-3-methylimidazolium
      hexafluorophosphate ([BMIM][PF6]) and 1-ethyl-3-methylimidazolium
      hexafluorophosphate ([EMIM][PF6]), were derived from periodic crystal phase
      calculations with density functional theory (DFT) and plane wave basis sets
      (denoted as "AIMD-c charge"). For both ILs, the total charge was found to be +/
      0.8 e for the cation and anion, respectively, due to the charge transfer between
      ions and polarization caused by the environment. These atomic charges were used
      in a force field developed within the general Amber force field framework. Using
      this force field, static, dynamic, and thermodynamic properties were computed for
      the two ILs using molecular dynamics simulation. The results were compared
      against results obtained using the same Amber force field but four different sets
      of partial charges, denoted as full charge, scaled charge, AIMD-l charge, and
      AIMD-b charge, respectively. The full charge was derived from quantum chemistry
      calculation of isolated ions in a vacuum and resulted in a total charge of unity
      on each ion. The scaled charge was obtained by uniformly scaling the full charge
      by 0.8. AIMD-l and AIMD-b charges were derived from liquid phase ab initio
      molecular dynamics simulations. The scaled charges have the same total charge on
      the ions as the AIMD-c charge but different distributions. It was found that
      simulation results not only depend on the total charge of each ion, but they are
      also sensitive to the charge distribution within an ion, especially for dynamic
      and thermodynamic properties. Overall, for the two ILs under study, the AIMD-c
      charge was found to predict experimental results better than the other four sets
      of charges, indicating that fitting charges from crystal phase DFT calculations,
      instead of extensive sampling of the liquid phase configurations, is a simple and
      reliable way to derive atomic charges for condensed phase ionic liquid
      simulations.

PMID- 22852553
TI  - The use of small-bowel capsule endoscopy in iron-deficiency anemia alone; be
      aware of the young anemic patient.
AB  - BACKGROUND & AIM: The role of Small-Bowel Capsule Endoscopy (SBCE) in Iron
      Deficiency Anemia (IDA) alone is still under validation. We aim to assess the
      usefulness of SBCE in patients with IDA alone. METHODS: Retrospective study;
      patients with IDA (no GI symptoms or known previous diagnosis), who underwent
      SBCE were included. SBCE findings were classified as clinically
      significant/sinister (small-bowel malignancy, significant/sinister inflammation
      and/or strictures and coeliac disease) or vascular, i.e.,
      signifcant/angioectasias (P1/P2 lesions). RESULTS: A total of 221 (151F/70M)
      patients had SBCE for IDA as the sole indication. The diagnostic yield (DY) was
      30.7% (68/221). The DY for significant/sinister pathology and
      significant/angioectasias was 9% and 21.7%, respectively. In those <= 40 years
      (20; 13F/7M), significant pathology was found in 25% (5/20); in the >40-year
      group (201; 138F/63M), significant/sinister pathology was found in 7.5% (15/201),
      p = 0.0231. None of the patients <=40 years had angioectasias, such lesions were
      found in 48/201 (21.7%) of those >40 years, p = 0.009. Fifty percent of those >80
      years (16; 12F/4M) had angioectasias, but none had significant/sinister pathology
      (p = 0.0126). On multiple regression analysis, only prior blood transfusion was
      predictive of higher DY in SBCE. CONCLUSIONS: IDA alone is one of the main
      indications (27%) for referral to SBCE; the majority of patients are >40 years.
      In our cohort, the DY of SBCE for IDA was 30.7% and the commonest finding was
      angioectasias. The detection rate of sinister small-bowel pathology for those >40
      years is low decreasing to zero in the >80 age group. In contrast, 25% of those
      <=40 years had a sinister diagnosis.

PMID- 22852555
TI  - Investigation of possible endogenous hypoxia markers in colorectal cancer.
AB  - OBJECTIVE: We evaluated the potential of some recently proposed hypoxia markers,
      being monocarboxylic acid transporter 1 (MCT1), MCT4 and prolyl hydroxylase 2
      (PHD2); and a more established hypoxia marker, glucose transporter-1 (GLUT-1), by
      testing the association with the exogenous marker pimonidazole. MATERIALS AND
      METHODS: Paraffin embedded tumour sections of 20 colorectal cancer patients were
      stained for blood vessels together with either pimonidazole or carbonic anhydrase
      IX (CA-IX) and single stained for MCT1, MCT4, GLUT-1, and PHD2. Expression of all
      markers was compared with expression of pimonidazole and micro-vessel density
      (MVD) and with disease-free survival (DFS) and overall survival (OS). RESULTS: No
      correlation was found between the different intrinsic hypoxia markers tested and
      pimonidazole. A trend for high MCT1 expression in biopsies with low CA-IX
      expression was found (R = -0.45, p = 0.06) and also the expression of MCT1 was
      higher in tumours with a high MVD (R = 0.49, p = 0.04). The more advanced tumours
      showed a higher expression of GLUT-1 (p = 0.03). A low CA-IX expression in the
      tumour correlated with better DFS (p = 0.03) and related to better OS (p = 0.07).
      CONCLUSION: Although none of the tested intrinsic hypoxia markers correlated with
      pimonidazole staining, we confirmed the important role of both GLUT-1 and CA-IX
      for a more advanced pTNM (pathological tumour-node-metastasis) stage and DFS
      respectively.

PMID- 22852556
TI  - Self-reported health and physical activity among community mental healthcare
      users.
AB  - The aim of the study was to survey the self-reported health and physical activity
      in a sample of community mental healthcare users in a city of Sweden. The study
      was conducted through a cross-sectional design with participants requested to
      fill out a self-report questionnaire. Participants (n = 103) were persons with
      psychiatric disabilities living in residential psychiatric settings and/or
      participating in daily activities provided by community mental healthcare
      services. The results showed that the group is affected with serious risk
      factors, such as high body mass index, low rated extent and frequency of physical
      activity and low self-estimated general state of health. Even though some
      difficulties associated with the answering process of this questionnaire emerged,
      these self-reported results clearly confirm the fact that persons with
      psychiatric disabilities constitute a vulnerable group in need for health
      promoting caring activities and interventions.

PMID- 22852557
TI  - Si nanowires forest-based on-chip biomolecular filtering, separation and
      preconcentration devices: nanowires do it all.
AB  - The development of efficient biomolecular separation and purification techniques
      is of critical importance in modern genomics, proteomics, and biosensing areas,
      primarily due to the fact that most biosamples are mixtures of high diversity and
      complexity. Most of existent techniques lack the capability to rapidly and
      selectively separate and concentrate specific target proteins from a complex
      biosample, and are difficult to integrate with lab-on-a-chip sensing devices.
      Here, we demonstrate the development of an on-chip all-SiNW filtering, selective
      separation, desalting, and preconcentration platform for the direct analysis of
      whole blood and other complex biosamples. The separation of required protein
      analytes from raw biosamples is first performed using a antibody-modified
      roughness-controlled SiNWs (silicon nanowires) forest of ultralarge binding
      surface area, followed by the release of target proteins in a controlled liquid
      media, and their subsequent detection by supersensitive SiNW-based FETs arrays
      fabricated on the same chip platform. Importantly, this is the first
      demonstration of an all-NWs device for the whole direct analysis of blood samples
      on a single chip, able to selectively collect and separate specific low abundant
      proteins, while easily removing unwanted blood components (proteins, cells) and
      achieving desalting effects, without the requirement of time-consuming
      centrifugation steps, the use of desalting or affinity columns. Futhermore, we
      have demonstrated the use of our nanowire forest-based separation device,
      integrated in a single platform with downstream SiNW-based sensors arrays, for
      the real-time ultrasensitive detection of protein biomarkers directly from blood
      samples. The whole ultrasensitive protein label-free analysis process can be
      practically performed in less than 10 min.

PMID- 22852558
TI  - Estimating the malaria transmission of Plasmodium vivax based on serodiagnosis.
AB  - BACKGROUND: Plasmodium vivax re-emerged in 1993 and has now become a major public
      health problem during the summer season in South Korea. The aim of this study was
      to interpret and understand the meaning of seroepidemiological studies for
      developing the best malaria control programme in South Korea. METHODS: Blood
      samples were collected in Gimpo city, Paju city, Yeoncheon County, Cheorwon
      County and Goseong County of high risk area in South Korea. Microscopy was
      performed to identify patients infected with P. vivax. Antibody detection for P.
      vivax was performed using indirect fluorescent antibody test (IFAT). RESULTS: A
      total of 1,574 blood samples was collected from participants in the study areas
      and evaluated against three parameters: IFAT positive rate, annual antibody
      positive index (AAPI), and annual parasite index (API). The IFAT positive rate
      was 7.24% (n = 114). Of the five study areas, Gimpo had the highest IFAT positive
      rate (13.68%) and AAPI (4.63). Yeongcheon had the highest API in 2005 (2.06)
      while Gimpo had the highest API in 2006 (5.00). No correlation was observed
      between any of the three parameters and study sites' distance from the
      demilitarized zone (DMZ). CONCLUSIONS: These results showed that P. vivax
      antibody levels could provide useful information about the prevalence of malaria
      in endemic areas. Furthermore, AAPI results for each year showed a closer
      relationship to API the following year than the API of the same year and thus
      could be helpful in predicting malaria transmission risks.

PMID- 22852559
TI  - Appropriate patient instructions can reduce prostate motion.
AB  - BACKGROUND: Interfraction prostate motion must be compensated by increased safety
      margins. If filling status of rectum and bladder is constant, motion should be
      reduced. We attempted to reduce interfraction motion errors by proper patient
      instruction. METHOD: In 38 patients pairs of radio-opaque fiducial markers were
      implanted prior to definitive radiotherapy. Patients were positioned either
      according to skin marks or infrared body marker. We measured prostate
      displacement, i.e. pelvic bones versus intraprostatic marker position, via
      ExacTrac (two orthogonal radiographies) in 1252 fractions. Systematic and random
      setup and displacement errors were determined and safety margins estimated.
      RESULTS: In our study interfraction prostate displacement is < 1 mm in RL
      direction, and < 2 mm in AP and SI direction. Systematic errors are slightly
      below random errors (< 1.5 mm). Positioning according skin marks results in
      higher inaccuracies of +/-1.5 - 2 mm in RL and +/-2 - 2.5 mm in AP/SI direction.
      CONCLUSIONS: In case of appropriate patient instructions (constant organ filling)
      the positioning via bone fusion requires CTV-PTV margins of 2 mm in RL, 4 mm in
      AP, and 5 mm in SI direction. Studies without any description of patient
      instruction found much higher margins of > 1 cm in AP and SI direction.

PMID- 22852563
TI  - Support for network to advance veterinary medical research.

PMID- 22852560
TI  - Examining the impact of genetic testing for type 2 diabetes on health behaviors:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: We describe the study design, procedures, and development of the risk
      counseling protocol used in a randomized controlled trial to evaluate the impact
      of genetic testing for diabetes mellitus (DM) on psychological, health behavior,
      and clinical outcomes. METHODS/DESIGN: Eligible patients are aged 21 to 65 years
      with body mass index (BMI) >=27 kg/m(2) and no prior diagnosis of DM. At
      baseline, conventional DM risk factors are assessed, and blood is drawn for
      possible genetic testing. Participants are randomized to receive conventional
      risk counseling for DM with eye disease counseling or with genetic test results.
      The counseling protocol was pilot tested to identify an acceptable graphical
      format for conveying risk estimates and match the length of the eye disease to
      genetic counseling. Risk estimates are presented with a vertical bar graph
      denoting risk level with colors and descriptors. After receiving either genetic
      counseling regarding risk for DM or control counseling on eye disease, brief
      lifestyle counseling for prevention of DM is provided to all participants.
      DISCUSSION: A standardized risk counseling protocol is being used in a randomized
      trial of 600 participants. Results of this trial will inform policy about whether
      risk counseling should include genetic counseling. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT01060540.

PMID- 22852564
TI  - Is complementary and alternative medicine compatible with evidence-based
      medicine?

PMID- 22852565
TI  - What is your diagnosis? Chronic wooden foreign body.

PMID- 22852566
TI  - ECG of the Month. Second-degree atrioventricular block in a cat.

PMID- 22852567
TI  - Theriogenology question of the month. Preputial edema in a bull after injury.

PMID- 22852568
TI  - Pathology in practice. Encephalitic listeriosis.

PMID- 22852570
TI  - Effects of two training curricula on basic laparoscopic skills and surgical
      performance among veterinarians.
AB  - OBJECTIVE: To compare laparoscopic skills among veterinarians before and after
      undertaking 1 of 2 programs of simulation training. DESIGN: Evaluation study.
      SAMPLE POPULATION: 17 veterinarians at 1 institution. PROCEDURES: Basic skills
      were tested by use of the McGill inanimate system for training and evaluation of
      laparoscopic skills (MISTELS). Surgical performance was assessed through an
      objective structured assessment of technical skills (OSATS). Both tests were
      performed prior to and after a 12-session training program, consisting of MISTELS
      exercises (curriculum A) or a variety of exercises (curriculum B). RESULTS:
      Curriculum B led to improvement of scores obtained with both the MISTELS and the
      OSATS. Curriculum A did not result in higher scores obtained with the MISTELS,
      compared with curriculum B. Curriculum A did not lead to an improvement of scores
      obtained with the OSATS. Participant-perceived value of the training program was
      correlated positively with the improvement of scores for MISTELS suturing tasks
      and scores obtained with the OSATS. Time spent in clinical laparoscopic surgery
      and curriculum B training were both positively correlated with the post-training
      OSATS scores but not with post-training MISTELS scores. Conversely, simulation
      training time correlated with an increase in MISTELS scores but not OSATS scores.
      CONCLUSIONS AND CLINICAL RELEVANCE: MISTELS training resulted in significant
      improvement of basic laparoscopic skills but not in the assessment used for
      surgical performance. This may have been due to the small number of study
      participants, the assessment tool, or the method of training. A varied curriculum
      may be advantageous when training veterinarians for clinical laparoscopic
      practice.

PMID- 22852569
TI  - Pathology in practice. Lagenidium infection.

PMID- 22852571
TI  - Evaluation of splenectomy as a risk factor for gastric dilatation-volvulus.
AB  - OBJECTIVE: To evaluate whether dogs undergoing splenectomy had an increased risk
      of gastric dilatation-volvulus (GDV), compared with a control group of dogs
      undergoing enterotomy. DESIGN: Retrospective case-control study. ANIMALS: 219
      dogs that underwent splenectomy for reasons other than splenic torsion
      (splenectomy group; n = 172) or enterotomy (control group; 47) without concurrent
      gastropexy. PROCEDURES: Medical records were reviewed for information on
      signalment, date of surgery, durations of surgery and anesthesia, reason for
      splenectomy, histopathologic findings (if applicable), whether gastropexy was
      performed, duration of follow-up, and date of death (if applicable). Follow-up
      information, including occurrence of GDV, was obtained via medical records review
      and a written client questionnaire. RESULTS: Reasons for splenectomy included
      splenic neoplasia, nonneoplastic masses, infarction, traumatic injury, and
      adhesions to a gossypiboma. Incidence of GDV following surgery was not
      significantly different between dogs of the splenectomy (14/172 [8.1 %]) and
      control (3/47 [6.4%]) groups. Median time to GDV for the 17 affected dogs was 352
      days (range, 12 to 2,368 days) after surgery. Among dogs that underwent
      splenectomy, sexually intact males had a significantly higher incidence of GDV
      (4/16) than did castrated males and sexually intact or spayed females (10/156).
      Incidence of GDV among sexually intact male dogs did not differ between groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results did not support a recommendation for
      routine use of prophylactic gastropexy in dogs at the time of splenectomy. Other
      patient-specific risk factors should be assessed prior to recommending this
      procedure.

PMID- 22852572
TI  - Use of pleural access ports for treatment of recurrent pneumothorax in two dogs.
AB  - CASE DESCRIPTION: An 8-year-old castrated male mixed-breed dog (dog 1) and a 13
      year-old spayed female mixed-breed dog (dog 2) were evaluated because of
      spontaneous pneumothorax. CLINICAL FINDINGS: Both dogs had decreased
      bronchovesicular sounds with coughing, tachypnea, cyanosis, lethargy, or a
      combination of these clinical signs. Radiographic examination revealed
      pneumothorax in both dogs and consolidation of a lung lobe in dog 2. Pneumothorax
      was alleviated following thoracocentesis in both dogs but recurred. TREATMENT AND
      OUTCOME: Dog 1 was initially treated by placement of a thoracostomy tube but
      underwent thoracotomy when pneumothorax recurred after tube removal; left caudal
      lung lobectomy was performed because a ruptured bulla was suspected, and a
      pulmonary bulla was histologically confirmed. Dog 2 underwent thoracotomy with
      left caudal lung lobectomy and partial removal of the left cranial lung lobe;
      diffuse pulmonary emphysema was diagnosed. This dog underwent a second surgery
      for right caudal lung lobectomy because of torsion. When pneumothorax recurred
      and additional surgery was not considered feasible, pleural access ports were
      placed in both dogs for repeated removal of air from the thoracic cavity. Ports
      were used clinically for 17 days in dog 1 and 14 days in dog 2. Dog 1
      successfully underwent another surgery when pneumothorax recurred 18 days after
      port placement but was euthanized 17 months later when dyspnea and tachypnea
      recurred. Pneumothorax had not recurred further in dog 2 twenty-three months
      after port placement. CLINICAL RELEVANCE: Findings suggested that pleural access
      ports may have a role in the management of spontaneous pneumothorax in dogs.

PMID- 22852573
TI  - Use of three-dimensional conformal radiation therapy for treatment of a heart
      base chemodectoma in a dog.
AB  - CASE DESCRIPTION: A 9-year-old spayed female mixed-breed dog was evaluated
      because of a progressively worsening, nonproductive cough and gagging of 1 year's
      duration. CLINICAL FINDINGS: Physical examination results were unremarkable. A
      cranial mediastinal mass was identified at the heart base with 3-view thoracic
      radiography. A CT scan of the thorax revealed an invasive mass surrounding major
      vessels at the heart base that was not considered surgically resectable.
      Thoracoscopic biopsy specimens of the cranial mediastinal mass were obtained, and
      histologic evaluation revealed that the tumor was a chemodectoma. TREATMENT AND
      OUTCOME: On the basis of results of the CT scan, a 3-D conformal radiation
      therapy plan was generated with computer treatment-planning software. The patient
      was treated with external beam radiation therapy; a 6-MV linear accelerator was
      used to deliver a prescribed dose of 57.5 Gy in twenty-three 2.5-Gy fractions.
      The cough improved following radiation therapy. Prior to treatment, the tumor
      volume was calculated to be 126.69 cm(3). Twenty-five months following radiation
      therapy, a follow-up CT scan was performed and there was a >50% reduction in
      tumor volume at that time. Disease progression causing pericardial, pleural, and
      peritoneal effusion and syncopal episodes occurred 32 months following radiation
      therapy, which were treated with pericardectomy and additional radiation therapy.
      The dog was still alive and doing well 42 months following initial radiation
      treatment. CLINICAL RELEVANCE: Conformal radiation therapy provided an additional
      treatment option for a nonresectable heart base chemodectoma in the dog of this
      report; conformal radiation therapy was reasonably tolerable and safe.

PMID- 22852574
TI  - Seizures and severe nutrient deficiencies in a puppy fed a homemade diet.
AB  - CASE DESCRIPTION: An 8-month-old male Saint Bernard developed tetanic seizures
      and hyperthermia during evaluation of bilateral osteochondritis dissecans of the
      shoulder joints. Further investigation revealed that the dog was receiving an
      unbalanced homemade diet. CLINICAL FINDINGS: Preliminary evaluation of the dog
      revealed bilateral signs of pain and mild muscle wasting in the shoulder joint
      areas. Serum biochemical analysis revealed severe hypocalcemia, hyponatremia,
      hypochloremia, hyperphosphatemia, vitamin D deficiency, and taurine deficiency.
      Diffuse osteopenia was identified on radiographs of the mandible and long bones,
      confirming bone demineralization. Analysis of the homemade diet revealed that the
      dog's diet was severely deficient in a variety of nutrients. TREATMENT AND
      OUTCOME: The dog responded positively to treatment for hypocalcemia,
      hyperthermia, and seizures. The dog's diet was changed to a complete and balanced
      canine diet formulated for growth. Body weight and body condition were monitored,
      and dietary intake was adjusted to achieve optimal body condition during growth.
      After initial evaluation, serial monitoring of serum calcium and taurine
      concentrations revealed that values were within reference limits and the dog had
      no further clinical signs associated with dietary deficiency. CLINICAL RELEVANCE:
      Findings in this puppy highlight the risks associated with feeding an unbalanced
      homemade diet during growth and the importance of obtaining a thorough dietary
      history from all patients. For owners who elect to feed a homemade diet, it is
      critical to have the homemade diet carefully formulated by a veterinary
      nutritionist to avoid severe nutrient imbalances, especially in young, growing
      dogs.

PMID- 22852575
TI  - Protective effects against abortion and fetal infection following exposure to
      bovine viral diarrhea virus and bovine herpesvirus 1 during pregnancy in beef
      heifers that received two doses of a multivalent modified-live virus vaccine
      prior to breeding.
AB  - OBJECTIVE: To determine whether administration of 2 doses of a multivalent,
      modified-live virus vaccine prior to breeding of heifers would provide protection
      against abortion and fetal infection following exposure of pregnant heifers to
      cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) and
      cattle with acute bovine herpesvirus 1 (BHV1) infection. DESIGN: Randomized
      controlled clinical trial. ANIMALS: 33 crossbred beef heifers, 3 steers, 6 bulls,
      and 25 calves. PROCEDURES: 20 of 22 vaccinated and 10 of 11 unvaccinated heifers
      became pregnant and were commingled with 3 steers PI with BVDV type 1a, 1b, or 2
      for 56 days beginning 102 days after the second vaccination (administered 30 days
      after the first vaccination). Eighty days following removal of BVDV-PI steers,
      heifers were commingled with 3 bulls with acute BHV1 infection for 14 days.
      RESULTS: After BVDV exposure, 1 fetus (not evaluated) was aborted by a vaccinated
      heifer; BVDV was detected in 0 of 19 calves from vaccinated heifers and in all 4
      fetuses (aborted after BHV1 exposure) and 6 calves from unvaccinated heifers.
      Bovine herpesvirus 1 was not detected in any fetus or calf and associated fetal
      membranes in either treatment group. Vaccinated heifers had longer gestation
      periods and calves with greater birth weights, weaning weights, average daily
      gains, and market value at weaning, compared with those for calves born to
      unvaccinated heifers. CONCLUSIONS AND CLINICAL RELEVANCE: Prebreeding
      administration of a modified-live virus vaccine to heifers resulted in fewer
      abortions and BVDV-PI offspring and improved growth and increased market value of
      weaned calves.

PMID- 22852576
TI  - Fecal shedding of Cryptosporidium oocysts in healthy alpaca crias and their dams.
AB  - OBJECTIVE: To determine the apparent prevalence of shedding of Cryptosporidium
      spp in healthy alpaca crias and their dams on 14 farms in New York and 1 farm in
      Pennsylvania. DESIGN: Cross-sectional study. ANIMALS: 110 alpaca crias and their
      110 dams. PROCEDURES: Fecal samples were obtained from 220 alpacas at 14 alpaca
      farms in New York and 1 farm in Pennsylvania. For each animal, age, sex, and
      health condition were recorded. A fecal score (1 = normally formed; 2 = soft or
      loose; 3 = diarrhetic) was recorded for each cria. Cryptosporidium oocysts were
      identified in fecal samples by a direct immunofluorescence assay. RESULTS:
      Apparent prevalence of fecal shedding of Cryptosporidium oocysts was 8% (95%
      confidence interval, 4% to 15%) in dams and was 7% (95% confidence interval, 3%
      to 13%) in crias. There was no significant difference in age between dams with
      positive fecal test results for Cryptosporidium oocysts (median age, 4 years;
      range, 3 to 8 years) and dams with negative results (median age, 4 years; range,
      2.5 to 19 years). No significant difference was found in age between crias with
      positive fecal test results (median age, 20 days; range, 7 to 53 days) and those
      with negative results (median, 36 days; range, 2 to 111 days). No significant
      difference in fecal scores was found between crias with positive versus negative
      fecal test results. CONCLUSIONS AND CLINICAL RELEVANCE: A higher than previously
      reported apparent prevalence of fecal shedding of Cryptosporidium oocysts in
      healthy alpacas was found. A zoonotic risk should be considered, especially for
      Cryptosporidium parvum.

PMID- 22852577
TI  - Do knowledge, knowledge sources and reasoning skills affect the accuracy of
      nursing diagnoses? a randomised study.
AB  - BACKGROUND: This paper reports a study about the effect of knowledge sources,
      such as handbooks, an assessment format and a predefined record structure for
      diagnostic documentation, as well as the influence of knowledge, disposition
      toward critical thinking and reasoning skills, on the accuracy of nursing
      diagnoses.Knowledge sources can support nurses in deriving diagnoses. A nurse's
      disposition toward critical thinking and reasoning skills is also thought to
      influence the accuracy of his or her nursing diagnoses. METHOD: A randomised
      factorial design was used in 2008-2009 to determine the effect of knowledge
      sources. We used the following instruments to assess the influence of ready
      knowledge, disposition, and reasoning skills on the accuracy of diagnoses: (1) a
      knowledge inventory, (2) the California Critical Thinking Disposition Inventory,
      and (3) the Health Science Reasoning Test. Nurses (n = 249) were randomly
      assigned to one of four factorial groups, and were instructed to derive diagnoses
      based on an assessment interview with a simulated patient/actor. RESULTS: The use
      of a predefined record structure resulted in a significantly higher accuracy of
      nursing diagnoses. A regression analysis reveals that almost half of the variance
      in the accuracy of diagnoses is explained by the use of a predefined record
      structure, a nurse's age and the reasoning skills of 'deduction' and 'analysis'.
      CONCLUSIONS: Improving nurses' dispositions toward critical thinking and
      reasoning skills, and the use of a predefined record structure, improves accuracy
      of nursing diagnoses.

PMID- 22852578
TI  - Production of fungal and bacterial growth modulating secondary metabolites is
      widespread among mycorrhiza-associated streptomycetes.
AB  - BACKGROUND: Studies on mycorrhiza associated bacteria suggest that bacterial
      fungal interactions play important roles during mycorrhiza formation and affect
      plant health. We surveyed Streptomyces Actinobacteria, known as antibiotic
      producers and antagonists of fungi, from Norway spruce mycorrhizas with
      predominantly Piloderma species as the fungal partner. RESULTS: Fifteen
      Streptomyces isolates exhibited substantial variation in inhibition of tested
      mycorrhizal and plant pathogenic fungi (Amanita muscaria, Fusarium oxysporum,
      Hebeloma cylindrosporum, Heterobasidion abietinum, Heterobasidion annosum,
      Laccaria bicolor, Piloderma croceum). The growth of the mycorrhiza-forming fungus
      Laccaria bicolor was stimulated by some of the streptomycetes, and Piloderma
      croceum was only moderately affected. Bacteria responded to the streptomycetes
      differently than the fungi. For instance the strain Streptomyces sp. AcM11, which
      inhibited most tested fungi, was less inhibitory to bacteria than other tested
      streptomycetes. The determined patterns of Streptomyces-microbe interactions were
      associated with distinct patterns of secondary metabolite production. Notably,
      potentially novel metabolites were produced by strains that were less
      antagonistic to fungi. Most of the identified metabolites were antibiotics (e.g.
      cycloheximide, actiphenol) and siderophores (e.g. ferulic acid,
      desferroxiamines). Plant disease resistance was activated by a single
      streptomycete strain only. CONCLUSIONS: Mycorrhiza associated streptomycetes
      appear to have an important role in inhibiting the growth of fungi and bacteria.
      Additionally, our study indicates that the Streptomyces strains, which are not
      general antagonists of fungi, may produce still un-described metabolites.

PMID- 22852579
TI  - Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy
      volunteers and depressed patients: a summary and method analysis of bridging
      research in support of phase II dose selection.
AB  - BACKGROUND: A key challenge to dose selection in early central nervous system
      (CNS) clinical drug development is that patient tolerability profiles often
      differ from those of healthy volunteers (HVs), yet HVs are the modal population
      for determining doses to be investigated in phase II trials. Without clear
      tolerability data from the target patient population, first efficacy trials may
      include doses that are either too high or too low, creating undue risk for study
      participants and the development program overall. Bridging trials address this
      challenge by carefully investigating safety and tolerability in the target
      population prior to full-scale proof-of-concept trials. OBJECTIVE: Org 26576 is
      an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
      positive allosteric modulator that acts by modulating ionotropic AMPA-type
      glutamate receptors to enhance glutamatergic neurotransmission. In preparation
      for phase II efficacy trials in major depressive disorder (MDD), two separate
      phase I trials were conducted to evaluate safety, tolerability, and
      pharmacokinetics in HVs and in the target patient population. METHODS: Both
      trials were randomized and placebo controlled, and included multiple rising-dose
      cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and
      patients with MDD (n = 54) were dosed under similarly controlled conditions in an
      inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days.
      Safety, tolerability, and pharmacokinetics were assessed frequently. RESULTS:
      Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in
      depressed patients was 450 mg bid, twice the MTD established in HVs. No
      clinically relevant safety issues associated with Org 26576 were noted.
      CONCLUSION: This article presents safety, tolerability, and pharmacokinetic data
      from two different populations examined under similar dosing conditions. The
      important implications of such bridging work in phase II dose selection are
      discussed, as are study design and data interpretation challenges.

PMID- 22852580
TI  - Efficacy of a non-hormonal treatment, BRN-01, on menopausal hot flashes: a
      multicenter, randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Homeopathic medicines have a place among the non-hormonal therapies
      for the treatment of hot flashes during the menopause. OBJECTIVE: The objective
      of this study was to evaluate the efficacy of the non-hormonal treatment BRN-01
      in reducing hot flashes in menopausal women. STUDY DESIGN: This was a
      multicenter, randomized, double-blind, placebo-controlled study carried out
      between June 2010 and July 2011. SETTING: The study was conducted in 35 active
      centers in France (gynecologists in private practice). PATIENTS: One hundred and
      eight menopausal women, >= 50 years of age, were enrolled in the study. The
      eligibility criteria included menopause for <24 months and >= 5 hot flashes per
      day with a significant negative effect on the women's professional and/or
      personal life. INTERVENTION: Treatment was either BRN-01 tablets, a registered
      homeopathic medicine containing Actaea racemosa (4 centesimal dilutions [4CH]),
      Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria
      canadensis (4CH), or identical placebo tablets, prepared by Laboratoires Boiron
      according to European Pharmacopoeia standards. Oral treatment (2 to 4 tablets per
      day) was started on day 3 after study enrollment and was continued for 12 weeks.
      MAIN OUTCOME MEASURE: The main outcome measure was the hot flash score (HFS)
      compared before, during, and after treatment. Secondary outcome criteria were the
      quality of life (QoL) [measured using the Hot Flash Related Daily Interference
      Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating
      Scale), evolution of the mean dosage, and compliance. All adverse events (AEs)
      were recorded. RESULTS: One hundred and one women were included in the final
      analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The
      global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted
      for baseline values, was significantly lower in the BRN-01 group than in the
      placebo group (mean +/- SD 88.2 +/- 6.5 versus 107.2 +/- 6.4; p = 0.0411). BRN-01
      was well tolerated; the frequency of AEs was similar in the two treatment groups,
      and no serious AEs were attributable to BRN-01. CONCLUSION: BRN-01 seemed to have
      a significant effect on the HFS, compared with placebo. According to the results
      of this clinical trial, BRN-01 may be considered a new therapeutic option with a
      safe profile for hot flashes in menopausal women who do not want or are not able
      to take hormone replacement therapy or other recognized treatments for this
      indication. Trial registration number (EudraCT): 2009-016959-21.

PMID- 22852581
TI  - The soy isoflavone genistein inhibits the reduction in Achilles tendon collagen
      content induced by ovariectomy in rats.
AB  - The objective of this study was to evaluate the effects of genistein and moderate
      intensity exercise on Achilles tendon collagen and cross-linking in intact and
      ovariectomized (OVX) female Sprague-Dawley rats. Rats were separated into eight
      groups (n = 9/group): intact or OVX, treadmill exercised or sedentary, genistein
      treated (300 mg/kg/day) or vehicle. After 6 weeks, tendons were assayed for the
      collagen-specific amino acid hydroxyproline and hydroxylyslpyridinoline (HP).
      Collagen content was not influenced by exercise (P = 0.40) but was lower (P <
      0.001) in OVX-vehicle rats compared with intact vehicle rats (OVX: 894 +/- 35 MUg
      collagen/mg dry weight; intact: 1185 +/- 72 MUg collagen/mg dry weight). In
      contrast, collagen content in OVX rats treated with genistein was greater (P =
      0.010, 1198 +/- 121 MUg collagen/mg dry weight) when compared with untreated rats
      and was not different from intact rats (P = 0.89). HP content was lower in OVX
      genistein-treated rats when compared with intact genistein-treated rats, but only
      within the sedentary animals (P = 0.05, intact-treated: 232 +/- 39 mmol/mol
      collagen; OVX-treated: 144 +/- 21 mmol/mol collagen). Our findings suggest that
      ovariectomy leads to a reduction in tendon collagen, which is prevented by
      genistein. HP content, however, may not have increased in proportion to the
      addition of collagen. Genistein may be useful for improving tendon collagen
      content in conditions of estrogen deficiency.

PMID- 22852582
TI  - Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide
      metabolism and produces a sulfane sulfur metabolite.
AB  - Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound enzyme that catalyzes
      the first step in the mitochondrial metabolism of H(2)S. Human SQOR is
      successfully expressed at low temperature in Escherichia coli by using an
      optimized synthetic gene and cold-adapted chaperonins. Recombinant SQOR contains
      noncovalently bound FAD and catalyzes the two-electron oxidation of H(2)S to S(0)
      (sulfane sulfur) using CoQ(1) as an electron acceptor. The prosthetic group is
      reduced upon anaerobic addition of H(2)S in a reaction that proceeds via a long
      wavelength-absorbing intermediate (lambda(max) = 673 nm). Cyanide, sulfite, or
      sulfide can act as the sulfane sulfur acceptor in reactions that (i) exhibit pH
      optima at 8.5, 7.5, or 7.0, respectively, and (ii) produce thiocyanate,
      thiosulfate, or a putative sulfur analogue of hydrogen peroxide (H(2)S(2)),
      respectively. Importantly, thiosulfate is a known intermediate in the oxidation
      of H(2)S by intact animals and the major product formed in glutathione-depleted
      cells or mitochondria. Oxidation of H(2)S by SQOR with sulfite as the sulfane
      sulfur acceptor is rapid and highly efficient at physiological pH
      (k(cat)/K(m,H(2)S) = 2.9 * 10(7) M(-1) s(-1)). A similar efficiency is observed
      with cyanide, a clearly artificial acceptor, at pH 8.5, whereas a 100-fold lower
      value is seen with sulfide as the acceptor at pH 7.0. The latter reaction is
      unlikely to occur in healthy individuals but may become significant under certain
      pathological conditions. We propose that sulfite is the physiological acceptor of
      the sulfane sulfur and that the SQOR reaction is the predominant source of the
      thiosulfate produced during H(2)S oxidation by mammalian tissues.

PMID- 22852583
TI  - ParsEval: parallel comparison and analysis of gene structure annotations.
AB  - BACKGROUND: Accurate gene structure annotation is a fundamental but somewhat
      elusive goal of genome projects, as witnessed by the fact that (model) genomes
      typically undergo several cycles of re-annotation. In many cases, it is not only
      different versions of annotations that need to be compared but also different
      sources of annotation of the same genome, derived from distinct gene prediction
      workflows. Such comparisons are of interest to annotation providers, prediction
      software developers, and end-users, who all need to assess what is common and
      what is different among distinct annotation sources. We developed ParsEval, a
      software application for pairwise comparison of sets of gene structure
      annotations. ParsEval calculates several statistics that highlight the
      similarities and differences between the two sets of annotations provided. These
      statistics are presented in an aggregate summary report, with additional details
      provided as individual reports specific to non-overlapping, gene-model-centric
      genomic loci. Genome browser styled graphics embedded in these reports help
      visualize the genomic context of the annotations. Output from ParsEval is both
      easily read and parsed, enabling systematic identification of problematic gene
      models for subsequent focused analysis. RESULTS: ParsEval is capable of analyzing
      annotations for large eukaryotic genomes on typical desktop or laptop hardware.
      In comparison to existing methods, ParsEval exhibits a considerable performance
      improvement, both in terms of runtime and memory consumption. Reports from
      ParsEval can provide relevant biological insights into the gene structure
      annotations being compared. CONCLUSIONS: Implemented in C, ParsEval provides the
      quickest and most feature-rich solution for genome annotation comparison to date.
      The source code is freely available (under an ISC license) at
      http://parseval.sourceforge.net/.

PMID- 22852584
TI  - The Saskatchewan rural health study: an application of a population health
      framework to understand respiratory health outcomes.
AB  - BACKGROUND: Respiratory disease can impose a significant burden on the health of
      rural populations. The Saskatchewan Rural Health Study (SRHS) is a new large
      prospective cohort study of ages 6 and over currently being conducted in farming
      and non-farming communities to evaluate potential health determinants associated
      with respiratory outcomes in rural populations. In this article, we describe the
      rationale and methodology for the adult component.The study is being conducted
      over 5 years (2009-15) in two phases, baseline and longitudinal. The baseline
      survey consists of two components, adults and children. The adult component
      consists of a questionnaire-based evaluation of individual and contextual factors
      of importance to respiratory health in two sub populations (a Farm Cohort and a
      Small Town Cohort) of rural families in Saskatchewan Rural Municipalities (RMs).
      Clinical studies of lung function and allergy tests are being conducted on
      selected sub-samples of the two cohorts based on the positive response to the
      last question on the baseline questionnaire: "Would you be willing to be
      contacted about having breathing and/or allergy tests at a nearby location?". We
      adopted existing population health theory to evaluate individual factors,
      contextual factors, and principal covariates on the outcomes of chronic
      bronchitis, chronic obstructive pulmonary disease, asthma and obstructive sleep
      apnea. FINDINGS: Of the RMs selected to participate, 32 (89%) out of 36 RMs and
      15 (94%) out of 16 small towns within the RMs agreed to participate. Using the
      mail out survey method developed by Dillman, we obtained completed questionnaires
      from 4264 households (8261 individuals). We obtained lung function measurements
      on 1609 adults, allergy skin test information on 1615 adults; both measurements
      were available on 1549 adults. We observed differences between farm and non-farm
      rural residents with respect to individual, contextual factors and covariates.
      DISCUSSION: There are differences between farm and non-farm rural residents with
      respect to individual and contextual factors and other variables of importance.
      The findings of the SRHS will improve knowledge of respiratory disease etiology,
      assist in the development and targeting of prevention programs, and in planning
      health services with farm and small town populations.

PMID- 22852585
TI  - Differing trends in the association between obesity and self-reported health in
      Portugal and Switzerland. Data from national health surveys 1992-2007.
AB  - BACKGROUND: The escalating prevalence of obesity might prompt obese subjects to
      consider themselves as normal, as this condition is gradually becoming as
      frequent as normal weight. In this study, we aimed to assess the trends in the
      associations between obesity and self-rated health in two countries. METHODS:
      Data from the Portuguese (years 1995-6, 1998-6 and 2005-6) and Swiss (1992-3,
      1997, 2002 and 2007) National Health Surveys were used, corresponding to more
      than 130,000 adults (64,793 for Portugal and 65,829 for Switzerland). Body mass
      index and self-rated health were derived from self-reported data. RESULTS:
      Obesity levels were higher in Portugal (17.5% in 2005-6 vs. 8.9% in 2007 in
      Switzerland, p < 0.001) and increased in both countries. The prevalence of
      participants rating their health as "bad" or "very bad" was higher in Portugal
      than in Switzerland (21.8% in 2005-6 vs 3.9% in 2007, p < 0.001). In both
      countries, obese participants rated more frequently their health as "bad" or
      "very bad" than participants with regular weight. In Switzerland, the prevalence
      of "bad" or "very bad" rates among obese participants, increased from 6.5% in
      1992-3 to 9.8% in 2007, while in Portugal it decreased from 41.3% to 32.3%. After
      multivariate adjustment, the odds ratio (OR) of stating one self's health as
      "bad" or "very bad" among obese relative to normal weight participants, almost
      doubled in Switzerland: from 1.38 (95% confidence interval, CI: 1.01-1.87) in
      1992-3 to 2.64 (95% CI: 2.14-3.26) in 2007, and similar findings were obtained
      after sample weighting. Conversely, no such trend was found in Portugal: 1.35
      (95% CI: 1.23-1.48) in 1995-6 and 1.52 (95% CI: 1.37-1.70) in 2005-6. CONCLUSION:
      Obesity is increasing in Switzerland and Portugal. Obesity is increasingly
      associated with poorer self-health ratings in Switzerland but not in Portugal.

PMID- 22852586
TI  - Influence of obesity on efficacy and toxicity of induction chemotherapy in
      patients with newly diagnosed acute myeloid leukemia.
AB  - Increased body mass index (BMI) is associated with increased risk of treatment
      related complications and inferior overall survival in patients with acute
      myeloid leukemia (AML). We retrospectively evaluated the association between
      percentage of ideal body weight (IBW) and complete remission (CR) among 63 newly
      diagnosed, previously untreated patients with AML. The median percentage of ideal
      body weight was 121% (range 86-246%). Thirty-three percent of patients were obese
      (>= 130% IBW). In multivariate analysis, obesity was not associated with CR (odds
      ratio [OR] = 0.97, p = 0.88), overall survival (hazard ratio = 0.48, p = 0.52),
      platelet recovery by 30 days (OR = 1.14, p = 0.52) or neutrophil recovery by 30
      days (OR = 1.12, p = 0.60). Obesity was also not associated with any differences
      in non-hematologic toxicity. CR rates were not significantly different comparing
      patients not dose-adjusted to patients with obesity-related adjustments (CR = 86%
      vs. 67%, p = 0.55). Empiric dose reductions based on obesity did not result in
      significantly different CR rates.

PMID- 22852588
TI  - Is there a role for pharmacoeconomics in decision making?

PMID- 22852590
TI  - Communication: hydration structure and polarization of heavy alkali ions: a first
      principles molecular dynamics study of Rb+ and Cs+.
AB  - Hydration structure and polarization of Rb(+) and Cs(+) in liquid water at
      ambient conditions were studied by first principles molecular dynamics. Our
      systematic analysis of the relevant electronic structures, based on maximally
      localized Wannier functions, revealed that the dipole moment of H(2)O molecules
      in the first solvation shell of the ions slightly increases with increasing the
      atomic number. We also found that the polarization of heavy alkali ions,
      particularly Cs(+), tends to stabilize a peculiar asymmetric hydration structure
      with relevant consequences in the extraction of the harmful (137)Cs resulting
      from nuclear wastes.

PMID- 22852587
TI  - New clinical insights into chronic obstructive pulmonary disease and their
      implications for pharmacoeconomic analyses.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      death and disability worldwide, but before the development of several new
      pharmacological treatments little could be done for COPD patients. Recognition
      that these new treatments could significantly improve the prognosis for COPD
      patients has radically changed clinical management guidelines from a palliative
      philosophy to an aggressive approach intended to reduce chronic symptoms, improve
      quality of life and prolong survival. These new treatments have also sparked
      interest in COPD cost-effectiveness research. Most COPD cost-effectiveness
      studies have been based on clinical trial populations, limited to direct medical
      costs, and used standard analysis methods such as Markov modelling, and they have
      usually found that newer therapies have favourable cost effectiveness. However,
      new insights into the clinical progression of COPD bring into question some of
      the assumptions underlying older analyses. In this review, we examine clinical
      factors unique to COPD and recent changes in clinical perspectives that have
      important implications for pharmacoeconomic analyses. The main parameters
      explored include (i) the high indirect medical costs for COPD and their relevance
      in assessing the societal benefits of new therapy; (ii) the importance of acute
      deteriorations in COPD, known as exacerbations, and approaches to modelling the
      cost benefit of exacerbation reduction; (iii) quality/utility instruments for
      COPD; (iv) the prevalence of co-morbid conditions and confounding between COPD
      and co-morbid disease utilization; (v) the limitations of Markov modelling; and
      (vi) the problem of outliers.

PMID- 22852592
TI  - Nonequilibrium molecular dynamics simulation of water transport through carbon
      nanotube membranes at low pressure.
AB  - Nonequilibrium molecular dynamics (NEMD) simulations are used to investigate
      pressure-driven water flow passing through carbon nanotube (CNT) membranes at low
      pressures (5.0 MPa) typical of real nanofiltration (NF) systems. The CNT membrane
      is modeled as a simplified NF membrane with smooth surfaces, and uniform straight
      pores of typical NF pore sizes. A NEMD simulation system is constructed to study
      the effects of the membrane structure (pores size and membrane thickness) on the
      pure water transport properties. All simulations are run under operating
      conditions (temperature and pressure difference) similar to a real NF processes.
      Simulation results are analyzed to obtain water flux, density, and velocity
      distributions along both the flow and radial directions. Results show that water
      flow through a CNT membrane under a pressure difference has the unique transport
      properties of very fast flow and a non-parabolic radial distribution of
      velocities which cannot be represented by the Hagen-Poiseuille or Navier-Stokes
      equations. Density distributions along radial and flow directions show that water
      molecules in the CNT form layers with an oscillatory density profile, and have a
      lower average density than in the bulk flow. The NEMD simulations provide direct
      access to dynamic aspects of water flow through a CNT membrane and give a view of
      the pressure-driven transport phenomena on a molecular scale.

PMID- 22852593
TI  - Tensor hypercontraction density fitting. I. Quartic scaling second- and third
      order Moller-Plesset perturbation theory.
AB  - Many approximations have been developed to help deal with the O(N(4)) growth of
      the electron repulsion integral (ERI) tensor, where N is the number of one
      electron basis functions used to represent the electronic wavefunction. Of these,
      the density fitting (DF) approximation is currently the most widely used despite
      the fact that it is often incapable of altering the underlying scaling of
      computational effort with respect to molecular size. We present a method for
      exploiting sparsity in three-center overlap integrals through tensor
      decomposition to obtain a low-rank approximation to density fitting (tensor
      hypercontraction density fitting or THC-DF). This new approximation reduces the
      4th-order ERI tensor to a product of five matrices, simultaneously reducing the
      storage requirement as well as increasing the flexibility to regroup terms and
      reduce scaling behavior. As an example, we demonstrate such a scaling reduction
      for second- and third-order perturbation theory (MP2 and MP3), showing that both
      can be carried out in O(N(4)) operations. This should be compared to the usual
      scaling behavior of O(N(5)) and O(N(6)) for MP2 and MP3, respectively. The THC-DF
      technique can also be applied to other methods in electronic structure theory,
      such as coupled-cluster and configuration interaction, promising significant
      gains in computational efficiency and storage reduction.

PMID- 22852591
TI  - Grid inhomogeneous solvation theory: hydration structure and thermodynamics of
      the miniature receptor cucurbit[7]uril.
AB  - The displacement of perturbed water upon binding is believed to play a critical
      role in the thermodynamics of biomolecular recognition, but it is nontrivial to
      unambiguously define and answer questions about this process. We address this
      issue by introducing grid inhomogeneous solvation theory (GIST), which
      discretizes the equations of inhomogeneous solvation theory (IST) onto a three
      dimensional grid situated in the region of interest around a solute molecule or
      complex. Snapshots from explicit solvent simulations are used to estimate
      localized solvation entropies, energies, and free energies associated with the
      grid boxes, or voxels, and properly summing these thermodynamic quantities over
      voxels yields information about hydration thermodynamics. GIST thus provides a
      smoothly varying representation of water properties as a function of position,
      rather than focusing on hydration sites where solvent is present at high density.
      It therefore accounts for full or partial displacement of water from sites that
      are highly occupied by water, as well as for partly occupied and water-depleted
      regions around the solute. GIST can also provide a well-defined estimate of the
      solvation free energy and therefore enables a rigorous end-states analysis of
      binding. For example, one may not only use a first GIST calculation to project
      the thermodynamic consequences of displacing water from the surface of a receptor
      by a ligand, but also account, in a second GIST calculation, for the
      thermodynamics of subsequent solvent reorganization around the bound complex. In
      the present study, a first GIST analysis of the molecular host cucurbit[7]uril is
      found to yield a rich picture of hydration structure and thermodynamics in and
      around this miniature receptor. One of the most striking results is the
      observation of a toroidal region of high water density at the center of the
      host's nonpolar cavity. Despite its high density, the water in this toroidal
      region is disfavored energetically and entropically, and hence may contribute to
      the known ability of this small receptor to bind guest molecules with unusually
      high affinities. Interestingly, the toroidal region of high water density
      persists even when all partial charges of the receptor are set to zero. Thus,
      localized regions of high solvent density can be generated in a binding site
      without strong, attractive solute-solvent interactions.

PMID- 22852594
TI  - A multiconfigurational hybrid density-functional theory.
AB  - We propose a multiconfigurational hybrid density-functional theory which
      rigorously combines a multiconfiguration self-consistent-field calculation with a
      density-functional approximation based on a linear decomposition of the electron
      electron interaction. This gives a straightforward extension of the usual hybrid
      approximations by essentially adding a fraction lambda of exact static
      correlation in addition to the fraction lambda of exact exchange. Test
      calculations on the cycloaddition reactions of ozone with ethylene or acetylene
      and the dissociation of diatomic molecules with the Perdew-Burke-Ernzerhof and
      Becke-Lee-Yang-Parr density functionals show that a good value of lambda is 0.25,
      as in the usual hybrid approximations. The results suggest that the proposed
      multiconfigurational hybrid approximations can improve over usual density
      functional calculations for situations with strong static correlation effects.

PMID- 22852595
TI  - On the precision of quasi steady state assumptions in stochastic dynamics.
AB  - Many biochemical networks have complex multidimensional dynamics and there is a
      long history of methods that have been used for dimensionality reduction for such
      reaction networks. Usually a deterministic mass action approach is used; however,
      in small volumes, there are significant fluctuations from the mean which the mass
      action approach cannot capture. In such cases stochastic simulation methods
      should be used. In this paper, we evaluate the applicability of one such
      dimensionality reduction method, the quasi-steady state approximation (QSSA) [L.
      Menten and M. Michaelis, "Die kinetik der invertinwirkung," Biochem. Z 49, 333369
      (1913)] for dimensionality reduction in case of stochastic dynamics. First, the
      applicability of QSSA approach is evaluated for a canonical system of enzyme
      reactions. Application of QSSA to such a reaction system in a deterministic
      setting leads to Michaelis-Menten reduced kinetics which can be used to derive
      the equilibrium concentrations of the reaction species. In the case of stochastic
      simulations, however, the steady state is characterized by fluctuations around
      the mean equilibrium concentration. Our analysis shows that a QSSA based approach
      for dimensionality reduction captures well the mean of the distribution as
      obtained from a full dimensional simulation but fails to accurately capture the
      distribution around that mean. Moreover, the QSSA approximation is not unique. We
      have then extended the analysis to a simple bistable biochemical network model
      proposed to account for the stability of synaptic efficacies; the substrate of
      learning and memory [J. E. Lisman, "A mechanism of memory storage insensitive to
      molecular turnover: A bistable autophosphorylating kinase," Proc. Natl. Acad.
      Sci. U.S.A. 82, 3055-3057 (1985)]. Our analysis shows that a QSSA based
      dimensionality reduction method results in errors as big as two orders of
      magnitude in predicting the residence times in the two stable states.

PMID- 22852597
TI  - A computationally efficacious free-energy functional for studies of inhomogeneous
      liquid water.
AB  - We present an accurate equation of state for water based on a simple microscopic
      Hamiltonian, with only four parameters that are well-constrained by bulk
      experimental data. With one additional parameter for the range of interaction,
      this model yields a computationally efficient free-energy functional for
      inhomogeneous water, which captures short-ranged correlations, cavitation
      energies, and, with suitable long-range corrections, the nonlinear dielectric
      response of water, making it an excellent candidate for the studies of mesoscale
      water and for use in ab initio solvation methods.

PMID- 22852598
TI  - Four-body interaction energy for compressed solid krypton from quantum theory.
AB  - The importance of the four-body contribution in compressed solid krypton was
      first evaluated using the many-body expansion method and the coupled cluster
      theory with full single and double excitations plus perturbative treatment of
      triples. All different four-atom clusters existing in the first- and second
      nearest neighbor shells of face-centered cubic krypton were considered, and both
      self-consistent-field Hartree-Fock and correlation parts of the four-body
      interaction were accurately determined from the ambient conditions up to
      eightfold volume compression. We find that the four-body interaction energy is
      negative at compression ratio lower than 2, where the dispersive forces play a
      dominant role. With increasing the compression, the four-body contribution
      becomes repulsive and significantly cancels the over-softening effects of the
      three-body potential. The obtained equation of state (EOS) was compared with the
      experiments and the density-functional theory calculations. It shows that
      combination of the four-body effects with two- and three-body interactions leads
      to an excellent agreement with EOS measurements throughout the whole experimental
      range 0-130 GPa, and extends the prediction to 300 GPa.

PMID- 22852596
TI  - Replica exchanging self-guided Langevin dynamics for efficient and accurate
      conformational sampling.
AB  - This work presents a replica exchanging self-guided Langevin dynamics (RXSGLD)
      simulation method for efficient conformational searching and sampling. Unlike
      temperature-based replica exchanging simulations, which use high temperatures to
      accelerate conformational motion, this method uses self-guided Langevin dynamics
      (SGLD) to enhance conformational searching without the need to elevate
      temperatures. A RXSGLD simulation includes a series of SGLD simulations, with
      simulation conditions differing in the guiding effect and/or temperature. These
      simulation conditions are called stages and the base stage is one with no guiding
      effect. Replicas of a simulation system are simulated at the stages and are
      exchanged according to the replica exchanging probability derived from the SGLD
      partition function. Because SGLD causes less perturbation on conformational
      distribution than high temperatures, exchanges between SGLD stages have much
      higher probabilities than those between different temperatures. Therefore, RXSGLD
      simulations have higher conformational searching ability than temperature based
      replica exchange simulations. Through three example systems, we demonstrate that
      RXSGLD can generate target canonical ensemble distribution at the base stage and
      achieve accelerated conformational searching. Especially for large systems,
      RXSGLD has remarkable advantages in terms of replica exchange efficiency,
      conformational searching ability, and system size extensiveness.

PMID- 22852599
TI  - Comparison of some dispersion-corrected and traditional functionals as applied to
      peptides and conformations of cyclohexane derivatives.
AB  - We compare the energetic and structural properties of fully optimized alpha
      helical and antiparallel beta-sheet polyalanines and the energetic differences
      between axial and equatorial conformations of three cyclohexane derivatives
      (methyl, fluoro, and chloro) as calculated using several functionals designed to
      treat dispersion (B97-D, omegaB97x-D, M06, M06L, and M06-2X) with other
      traditional functionals not specifically parametrized to treat dispersion (B3LYP,
      X3LYP, and PBE1PBE) and with experimental results. Those functionals developed to
      treat dispersion significantly overestimate interaction enthalpies of folding for
      the alpha-helix and predict unreasonable structures that contain Ramachandran phi
      and psi and C = O...N H-bonding angles that are out of the bounds of databases
      compiled the beta-sheets. These structures are consistent with overestimation of
      the interaction energies. For the cyclohexanes, these functionals overestimate
      the stabilities of the axial conformation, especially when used with smaller
      basis sets. Their performance improves when the basis set is improved from D95**
      to aug-cc-pVTZ (which would not be possible with systems as large as the
      peptides).

PMID- 22852601
TI  - An adaptive pseudospectral method for wave packet dynamics.
AB  - We solve the time-dependent Schrodinger equation for molecular dynamics using a
      pseudospectral method with global, exponentially decaying, Hagedorn basis
      functions. The approximation properties of the Hagedorn basis depend strongly on
      the scaling of the spatial coordinates. Using results from control theory we
      develop a time-dependent scaling which adaptively matches the basis to the wave
      packet. The method requires no knowledge of the Hessian of the potential. The
      viability of the method is demonstrated on a model for the photodissociation of
      IBr, using a Fourier basis in the bound state and Hagedorn bases in the
      dissociative states. Using the new approach to adapting the basis we are able to
      solve the problem with less than half the number of basis functions otherwise
      necessary. We also present calculations on a two-dimensional model of CO(2) where
      the new method considerably reduces the required number of basis functions
      compared to the Fourier pseudospectral method.

PMID- 22852600
TI  - Unrestricted Hartree-Fock based on the fragment molecular orbital method: energy
      and its analytic gradient.
AB  - A consideration of the surrounding environment is necessary for a meaningful
      analysis of the reaction activity in large molecular systems. We propose an
      approach to perform unrestricted Hartree-Fock (UHF) calculations within the
      framework of the fragment molecular orbital (FMO) method (FMO-UHF) to study large
      systems with unpaired electrons. Prior to an energy analysis one has to optimize
      geometry, which requires an accurate analytic energy gradient. We derive the FMO
      UHF energy and its analytic gradient and implement them into GAMESS. The
      performance of FMO-UHF is evaluated for a solvated organic molecule and a
      solvated metal complex, as well as for the active part of a protein, in terms of
      energy, gradient, and geometry optimization.

PMID- 22852602
TI  - Precise description of single and double ionization of hydrogen molecule in
      intense laser pulses.
AB  - A new simulation box setup is introduced for the precise description of the
      wavepacket evolution of two electronic systems in intense laser pulses. In this
      box, the regions of the hydrogen molecule H(2), and singly and doubly ionized
      species, H(2) (+) and H(2) (+2), are well discernible and their time-dependent
      populations are calculated at different laser field intensities. In addition,
      some new regions are introduced and characterized as quasi-double ionization and
      their time-dependencies on the laser field intensity are calculated and analyzed.
      The adopted simulation box setup is special in that it assures proper evaluation
      of the second ionization. In this study, the dynamics of the electrons and nuclei
      of the hydrogen molecule are separated based on the adiabatic approximation. The
      time-dependent Schrodinger and Newton equations are solved simultaneously for the
      electrons and the nuclei, respectively. Laser pulses of 390 nm wavelength at four
      different intensities (i.e., 1 * 10(14), 5 * 10(14), 1 * 10(15), and 5 * 10(15) W
      cm(-2)) are used in these simulations. Details of the central H(2) region are
      also presented and discussed. This region is divided into four sub-regions
      related to the ionic state H(+)H(-) and covalent (natural) state HH. The effect
      of the motion of nuclei on the enhanced ionization is discussed. Finally, some
      different time-dependent properties are calculated, their dependencies on the
      intensity of the laser pulse are studied, and their correlations with the
      populations of different regions are analyzed.

PMID- 22852604
TI  - Nuclear motion effects on the density matrix of crystals: an ab initio Monte
      Carlo harmonic approach.
AB  - In the frame of the Born-Oppenheimer approximation, nuclear motions in crystals
      can be simulated rather accurately using a harmonic model. In turn, the
      electronic first-order density matrix (DM) can be expressed as the statistically
      weighted average over all its determinations each resulting from an instantaneous
      nuclear configuration. This model has been implemented in a computational scheme
      which adopts an ab initio one-electron (Hartree-Fock or Kohn-Sham) Hamiltonian in
      the CRYSTAL program. After selecting a supercell of reasonable size and solving
      the corresponding vibrational problem in the harmonic approximation, a Metropolis
      algorithm is adopted for generating a sample of nuclear configurations which
      reflects their probability distribution at a given temperature. For each
      configuration in the sample the "instantaneous" DM is calculated, and its
      contribution to the observables of interest is extracted. Translational and point
      symmetry of the crystal as reflected in its average DM are fully exploited. The
      influence of zero-point and thermal motion of nuclei on such important first
      order observables as x-ray structure factors and Compton profiles can thus be
      estimated.

PMID- 22852603
TI  - Time-dependent quantum transport: an efficient method based on Liouville-von
      Neumann equation for single-electron density matrix.
AB  - Basing on our hierarchical equations of motion for time-dependent quantum
      transport [X. Zheng, G. H. Chen, Y. Mo, S. K. Koo, H. Tian, C. Y. Yam, and Y. J.
      Yan, J. Chem. Phys. 133, 114101 (2010)], we develop an efficient and accurate
      numerical algorithm to solve the Liouville-von-Neumann equation. We solve the
      real-time evolution of the reduced single-electron density matrix at the tight
      binding level. Calculations are carried out to simulate the transient current
      through a linear chain of atoms, with each represented by a single orbital. The
      self-energy matrix is expanded in terms of multiple Lorentzian functions, and the
      Fermi distribution function is evaluated via the Pade spectrum decomposition.
      This Lorentzian-Pade decomposition scheme is employed to simulate the transient
      current. With sufficient Lorentzian functions used to fit the self-energy
      matrices, we show that the lead spectral function and the dynamics response can
      be treated accurately. Compared to the conventional master equation approaches,
      our method is much more efficient as the computational time scales cubically with
      the system size and linearly with the simulation time. As a result, the
      simulations of the transient currents through systems containing up to one
      hundred of atoms have been carried out. As density functional theory is also an
      effective one-particle theory, the Lorentzian-Pade decomposition scheme developed
      here can be generalized for first-principles simulation of realistic systems.

PMID- 22852605
TI  - Linear-response theory for Mukherjee's multireference coupled-cluster method:
      static and dynamic polarizabilities.
AB  - The formalism of response theory is applied to derive expressions for static and
      dynamic polarizabilities within the state-specific multireference coupled-cluster
      theory suggested by Mukherjee and co-workers (Mk-MRCC) [J. Chem. Phys. 110, 6171
      (1998)]. We show that the redundancy problem inherent to Mk-MRCC theory gives
      rise to spurious poles in the Mk-MRCC response functions, which hampers the
      reliable calculation of dynamic polarizabilities. Furthermore, we demonstrate
      that in the case of a symmetry-breaking perturbation a working response theory is
      obtained only if certain internal excitations are included in the responses of
      the cluster amplitudes. Exemplary calculations within the singles and doubles
      approximation (Mk-MRCCSD) are carried out on aryne compounds to illustrate the
      impact of a multireference ansatz on the polarizability.

PMID- 22852606
TI  - Linear-response theory for Mukherjee's multireference coupled-cluster method:
      excitation energies.
AB  - The recently presented linear-response function for Mukherjee's multireference
      coupled-cluster method (Mk-MRCC) [T.-C. Jagau and J. Gauss, J. Chem. Phys. 137,
      044115 (2012)] is employed to determine vertical excitation energies within the
      singles and doubles approximation (Mk-MRCCSD-LR) for ozone as well as for o
      benzyne, m-benzyne, and p-benzyne, which display increasing multireference
      character in their ground states. In order to assess the impact of a
      multireference ground-state wavefunction on excitation energies, we compare all
      our results to those obtained at the single-reference coupled-cluster level of
      theory within the singles and doubles as well as within the singles, doubles, and
      triples approximation. Special attention is paid to the artificial splitting of
      certain excited states which arises from the redundancy intrinsic to Mk-MRCC
      theory and hinders the straightforward application of the Mk-MRCC-LR method.

PMID- 22852607
TI  - Fluctuating hydrodynamics for multiscale modeling and simulation: energy and heat
      transfer in molecular fluids.
AB  - This work illustrates that fluctuating hydrodynamics (FHD) simulations can be
      used to capture the thermodynamic and hydrodynamic responses of molecular fluids
      at the nanoscale, including those associated with energy and heat transfer. Using
      all-atom molecular dynamics (MD) trajectories as the reference data, the
      atomistic coordinates of each snapshot are mapped onto mass, momentum, and energy
      density fields on Eulerian grids to generate a corresponding field trajectory.
      The molecular length-scale associated with finite molecule size is explicitly
      imposed during this coarse-graining by requiring that the variances of density
      fields scale inversely with the grid volume. From the fluctuations of field
      variables, the response functions and transport coefficients encoded in the all
      atom MD trajectory are computed. By using the extracted fluid properties in FHD
      simulations, we show that the fluctuations and relaxation of hydrodynamic fields
      quantitatively match with those observed in the reference all-atom MD trajectory,
      hence establishing compatibility between the atomistic and field representations.
      We also show that inclusion of energy transfer in the FHD equations can more
      accurately capture the thermodynamic and hydrodynamic responses of molecular
      fluids. The results indicate that the proposed MD-to-FHD mapping with explicit
      consideration of finite molecule size provides a robust framework for coarse
      graining the solution phase of complex molecular systems.

PMID- 22852608
TI  - Free energy landscapes for the thermodynamic understanding of adsorption-induced
      deformations and structural transitions in porous materials.
AB  - Soft porous crystals are flexible metal-organic frameworks that respond to
      physical stimuli such as temperature, pressure, and gas adsorption by large
      changes in their structure and unit cell volume. While they have attracted a lot
      of interest, molecular simulation methods that directly couple adsorption and
      large structural deformations in an efficient manner are still lacking. We
      propose here a new Monte Carlo simulation method based on non-Boltzmann sampling
      in (guest loading, volume) space using the Wang-Landau algorithm, and show that
      it can be used to fully characterize the adsorption properties and the material's
      response to adsorption at thermodynamic equilibrium. We showcase this new method
      on a simple model of the MIL-53 family of breathing materials, demonstrating its
      potential and contrasting it with the pitfalls of direct, Boltzmann simulations.
      We furthermore propose an explanation for the hysteretic nature of adsorption in
      terms of free energy barriers between the two metastable host phases.

PMID- 22852609
TI  - Algebraic-diagrammatic construction polarization propagator approach to indirect
      nuclear spin-spin coupling constants.
AB  - A new polarization propagator approach to indirect nuclear spin-spin coupling
      constantans is formulated within the framework of the algebraic-diagrammatic
      construction (ADC) approximation and implemented at the level of the strict
      second-order approximation scheme, ADC(2). The ADC approach possesses transparent
      computational procedure operating with Hermitian matrix quantities defined with
      respect to physical excitations. It is size-consistent and easily extendable to
      higher orders via the hierarchy of available ADC approximation schemes. The
      ADC(2) method is tested in the first applications to HF, N(2), CO, H(2)O, HCN,
      NH(3), CH(4), C(2)H(2), PH(3), SiH(4), CH(3)F, and C(2)H(4). The calculated
      indirect nuclear spin-spin coupling constants are in good agreement with the
      experimental data and results of the second-order polarization propagator
      approximation method. The computational effort of the ADC(2) scheme scales as
      n(5) with respect to the number of molecular orbitals n, which makes this method
      promising for applications to larger molecules.

PMID- 22852610
TI  - Mixing coarse-grained and fine-grained water in molecular dynamics simulations of
      a single system.
AB  - The use of a supra-molecular coarse-grained (CG) model for liquid water as
      solvent in molecular dynamics simulations of biomolecules represented at the fine
      grained (FG) atomic level of modelling may reduce the computational effort by one
      or two orders of magnitude. However, even if the pure FG model and the pure CG
      model represent the properties of the particular substance of interest rather
      well, their application in a hybrid FG/CG system containing varying ratios of FG
      versus CG particles is highly non-trivial, because it requires an appropriate
      balance between FG-FG, FG-CG, and CG-CG energies, and FG and CG entropies. Here,
      the properties of liquid water are used to calibrate the FG-CG interactions for
      the simple-point-charge water model at the FG level and a recently proposed supra
      molecular water model at the CG level that represents five water molecules by one
      CG bead containing two interaction sites. Only two parameters are needed to
      reproduce different thermodynamic and dielectric properties of liquid water at
      physiological temperature and pressure for various mole fractions of CG water in
      FG water. The parametrisation strategy for the FG-CG interactions is simple and
      can be easily transferred to interactions between atomistic biomolecules and CG
      water.

PMID- 22852611
TI  - The effects of adsorbed water layers on the apparent height of nanostructures in
      ambient amplitude modulation atomic force microscopy.
AB  - Ambient amplitude modulation atomic force microscopy (AM AFM) is one of the most
      broadly used techniques as it is versatile and can provide measurements of single
      nanostructures routinely. Nevertheless, the technique typically measures an
      apparent height of nanostructures that does not coincide with the true height.
      Here, we carry out an exhaustive study of the several possibilities that arise in
      the presence and in the absence of adsorbed water layers when measuring the
      height of nanostructures. A method to control whether water layers are perturbed
      and whether intermittent mechanical contact occurs is provided. We show that the
      predicted range of apparent heights in the several interaction regimes is as
      large as the experimental values that are routinely obtained. In one extreme the
      apparent height might be larger than the true height even when sample deformation
      occurs. In the other, height reversal might occur even when sample deformation is
      much smaller than the loss of height. A main mechanism leading to such a broad
      range of measurements is identified in terms of the presence of water layers and
      the long range character of the resulting forces. In short, due to these long
      range effects, the gap in separation in the two amplitude branches, i.e., the
      attractive and the repulsive regimes, might be an order of magnitude larger in
      the presence of water than in its absence.

PMID- 22852612
TI  - Electronic structures of WAlO(y) and WAlO(y)(-) (y = 2-4) determined by anion
      photoelectron spectroscopy and density functional theory calculations.
AB  - The anion photoelectron spectra of WAlO(y)(-) (y = 2-4) are presented and
      assigned based on results of density functional theory calculations. The WAlO(2)(
      ) and WAlO(3)(-) spectra are both broad, with partially resolved vibrational
      structure. In contrast, the WAlO(4)(-) spectrum features well-resolved
      vibrational structure with contributions from three modes. There is reasonable
      agreement between experiment and theory for all oxides, and calculations are in
      particular validated by the near perfect agreement between the WAlO(4)(-)
      photoelectron spectrum and a Franck-Condon simulation based on computationally
      determined spectroscopic parameters. The structures determined from this study
      suggest strong preferential W-O bond formation, and ionic bonding between Al(+)
      and WO(y)(-2) for all anions. Neutral species are similarly ionic, with WAlO(2)
      and WAlO(3) having electronic structure that suggests Al(+) ionically bound to
      WO(y)(-) and WAlO(4) being described as Al(+2) ionically bound to WO(4)(-2). The
      doubly-occupied 3sp hybrid orbital localized on the Al center is energetically
      situated between the bonding O-local molecular orbitals and the anti- or non
      bonding W-local molecular orbitals. The structures determined in this study are
      very similar to structures recently determined for the analogous MoAlO(y)(
      )/MoAlO(y) cluster series, with subtle differences found in the electronic
      structures [S. E. Waller, J. E. Mann, E. Hossain, M. Troyer, and C. C. Jarrold,
      J. Chem. Phys. 137, 024302 (2012)].

PMID- 22852613
TI  - A crossed beam study of 18O(3P)+NO2 and 18O(1D)+NO2: isotope exchange and O2+NO
      formation channels.
AB  - The products and dynamics of the reactions (18)O((3)P)+NO(2) and
      (18)O((1)D)+NO(2) have been investigated using crossed beams and provide new
      constraints on the structures and lifetimes of the reactive nitrogen trioxide
      intermediates formed in collisions of O((3)P) and O((1)D) with NO(2). For each
      reaction, two product channels are observed - isotope exchange and O(2)+NO
      formation. From the measured product signal intensities at collision energies of
      ~6 to 9.5 kcal/mol, the branching ratio for O(2)+NO formation vs. isotope
      exchange for the O((3)P)+NO(2) reaction is 52(+6/-2)% to 48(+2/-6)%, while that
      for O((1)D)+NO(2) is 97(+2/-12)% to 3(+12/-2)%. The branching ratio for the
      O((3)P)+NO(2) reaction derived here is similar to the ratio measured in previous
      kinetics studies, while this is the first study in which the products of the
      O((1)D)+NO(2) reaction have been determined experimentally. Product energy and
      angular distributions are derived for the O((3)P)+NO(2) isotope exchange and the
      O((1)D)+NO(2)->O(2)+NO reactions. The results demonstrate that the O((3)P)+NO(2)
      isotope exchange reaction proceeds by an NO(3)* complex that is long-lived with
      respect to its rotational period and suggest that statistical incorporation of
      the reactant (18)O into the product NO(2) (apart from zero point energy isotope
      effects) likely occurs. In contrast, the (18)O((1)D)+NO(2)->O(2)+NO reaction
      proceeds by a direct "stripping" mechanism via a short-lived (18)O-O-NO* complex
      that results in the occurrence of (18)O in the product O(2) but not in the
      product NO. Similarly, (18)O is detected in O(2) but not NO for the O((3)P)+NO(2)
      >O(2)+NO reaction. Thus, even though the product energy and angular distributions
      for O((3)P)+NO(2)->O(2)+NO derived from the experimental data are uncertain,
      these results for isotope labeling under single collision conditions support
      previous kinetics studies that concluded that this reaction proceeds by an
      asymmetric (18)O-O-NO* intermediate and not by a long-lived symmetric NO(3)*
      complex, as earlier bulk isotope labeling experiments had concluded.
      Applicability of these results to atmospheric chemistry is also discussed.

PMID- 22852614
TI  - Mechanism of molecular orientation by single-cycle pulses.
AB  - Significant molecular orientation can be achieved by time-symmetric single-cycle
      pulses of zero area, in the THz region. We show that in spite of the existence of
      a combined time-space symmetry operation, not only large peak instantaneous
      orientations, but also nonzero time-average orientations, over a rotational
      period, can be obtained. We show that this unexpected phenomenon is due to
      interferences among eigenstates of the time-evolution operator, as was described
      previously for transport phenomena in quantum ratchets. This mechanism also works
      for appropriate sequences of identical pulses, spanning a rotational period. This
      fact can be used to obtain a net average molecular orientation regardless of the
      magnitude of the rotational constant.

PMID- 22852615
TI  - Size selective spectroscopy of Se microclusters.
AB  - The electronic structure and photofragmentation in outer and inner valence
      regions of Se(n) (n <= 8) clusters produced by direct vacuum evaporation have
      been studied with size-selective photoelectron-photoion coincidence technique by
      using vacuum-ultraviolet synchrotron radiation. The experimental ionization
      potentials of these clusters were extracted from the partial ion yield
      measurements. The calculations for the possible geometrical structures of the
      Se(n) microclusters have been executed. The ionization energies of the clusters
      have been calculated and compared with the experimental results. In addition,
      theoretical fragment ion appearance energies were estimated. The dissociation
      energies of Se(n) clusters were derived from the recurrent relation between the
      gas phase enthalpies of the formation of corresponding cationic clusters and
      experimental ionization energies.

PMID- 22852616
TI  - Direct dynamics simulation of dioxetane formation and decomposition via the
      singlet .O-O-CH2-CH2. biradical: non-RRKM dynamics.
AB  - Electronic structure calculations and direct chemical dynamics simulations are
      used to study the formation and decomposition of dioxetane on its ground state
      singlet potential energy surface. The stationary points for (1)O(2) + C(2)H(4),
      the singlet .O-O-CH(2)-CH(2). biradical, the transition state (TS) connecting
      this biradical with dioxetane, and the two transition states and gauche .O-CH(2)
      CH(2)-O. biradical connecting dioxetane with the formaldehyde product molecules
      are investigated at different levels of electronic structure theory including
      UB3LYP, UMP2, MRMP2, and CASSCF and a range of basis sets. The UB3LYP/6-31G*
      method was found to give representative energies for the reactive system and was
      used as a model for the simulations. UB3LYP/6-31G* direct dynamics trajectories
      were initiated at the TS connecting the .O-O-CH(2)-CH(2). biradical and dioxetane
      by sampling the TS's vibrational energy levels, and rotational and reaction
      coordinate energies, with Boltzmann distributions at 300, 1000, and 1500 K. This
      corresponds to the transition state theory model for trajectories that pass the
      TS. The trajectories were directed randomly towards both the biradical and
      dioxetane. A small fraction of the trajectories directed towards the biradical
      recrossed the TS and formed dioxetane. The remainder formed (1)O(2) + C(2)H(4)
      and of these ~ 40% went directly from the TS to (1)O(2) + C(2)H(4) without
      getting trapped and forming an intermediate in the .O-O-CH(2)-CH(2). biradical
      potential energy minimum, a non-statistical result. The dioxetane molecules which
      are formed dissociate to two formaldehyde molecules with a rate constant two
      orders of magnitude smaller than that predicted by Rice-Ramsperger-Kassel-Marcus
      theory. The reaction dynamics from dioxetane to the formaldehyde molecules do not
      follow the intrinsic reaction coordinate or involve trapping in the gauche .O
      CH(2)-CH(2)-O. biradical potential energy minimum. Important non-statistical
      dynamics are exhibited for this reactive system.

PMID- 22852617
TI  - A full-dimensional wave packet dynamics study of the photodetachment spectra of
      FCH4(-).
AB  - The low-resolution photodetachment spectrum of FCH(4)(-) is studied in full
      dimensionality employing the multi-configurational time-dependent Hartree
      approach and potential energy surfaces recently developed by Bowman and co
      workers. The computed spectrum qualitatively agrees with the low-resolution
      spectrum measured by Neumark and co-workers. It displays two peaks which can be
      assigned to different vibrational states of methane in the quasi-bound F.CH(4)
      van der Waals complex. The first intense peak correlates to methane in its
      vibrational ground state while the second much smaller peak results from methane
      where one of the bending modes is excited. The present simulations consider only
      a single potential energy surface for the neutral FCH(4) system and thus do not
      include spectral contributions arising from transitions to excited electronic
      states correlating to the F((2)P) + CH(4) asymptote. Considering the quantitative
      differences between the computed and the experimental spectra, one cannot decide
      whether beside the vibrational excitation of the methane fragment also electronic
      excitation of FCH(4) contributes to the second peak in the experimental
      photodetachment spectrum.

PMID- 22852618
TI  - Probing the structures and chemical bonding of boron-boronyl clusters using
      photoelectron spectroscopy and computational chemistry: B4(BO)(n)- (n = 1-3).
AB  - The electronic and structural properties of a series of boron oxide clusters,
      B(5)O(-), B(6)O(2)(-), and B(7)O(3)(-), are studied using photoelectron
      spectroscopy and density functional calculations. Vibrationally resolved
      photoelectron spectra are obtained, yielding electron affinities of 3.45, 3.54,
      and 4.94 eV for the corresponding neutrals, B(5)O, B(6)O(2), and B(7)O(3),
      respectively. Structural optimizations show that these oxide clusters can be
      formulated as B(4)(BO)(n)(-) (n = 1-3), which involve boronyls coordinated to a
      planar rhombic B(4) cluster. Chemical bonding analyses indicate that the
      B(4)(BO)(n)(-) clusters are all aromatic species with two pi electrons.

PMID- 22852619
TI  - B14(2+): a magic number double-ring cluster.
AB  - B(20) is a "magic number" cluster with double-ring structure. Surprisingly, we
      also find that B(14)(2+) is a "magic number" cluster with double-ring structure,
      which has the largest HOMO-LUMO gap (3.31 eV) and the highest aromaticity in
      double-ring clusters. This double-ring B(14)(2+) cluster is energetically lower
      than the quasi-planar one by even ~1.2 eV using high level ab initio
      calculations. B(14)(2+) also has 40 valence electrons as in Al(13)(-) cluster.
      The reason leading to the unusual properties of B(14)(2+) may be the electronic
      shell closing as in Al(13)(-) cluster based on the jellium model, besides the
      double aromaticity in all double-ring clusters.

PMID- 22852620
TI  - Theoretical characterization of the BN and BP coronenes by IR, Raman, and UV-VIS
      spectra.
AB  - Boron-nitrogen coronene (BNC) and boron-phosphorous coronene (BPC), not yet
      synthesized molecules and of possible interest for material science, are composed
      of six condensed rings of borazine and boraphosphabenzene molecules,
      respectively. They are similar to the carbon coronene molecule (CC). Moreover, CC
      and BNC are isoelectronic and the BPC is formally isoelectronic with respect to
      other coronenes, if only the valence electrons are considered. In this work, the
      BNC and BPC were theoretically characterized using IR, Raman, and UV-VIS
      spectroscopies. The coronenes studied have D(6h) and D(3h) symmetries for carbon
      and boron compounds, respectively. The calculated vibrational and electronic
      spectra for the CC are in good agreement with the experimental data, indicating
      that the calculations for BNC and BPC will be useful to identify these compounds,
      when synthesized. The main vibrational modes of the CC, BNC, and BPC are
      correlated. However, the BPC vibrational frequencies are substantially lower than
      the CC and BNC ones. The electronic ground state studies showed that the BPC has
      intermediate characteristics between the CC and BNC.

PMID- 22852621
TI  - A comprehensive study of the vibrationally resolved S 2p(-1) Auger electron
      spectrum of carbonyl sulfide.
AB  - High-resolution normal Auger-electron spectra of carbonyl sulfide subsequent to S
      2p(-1) photoionization at photon energies of 200, 220, and 240 eV are reported
      along with corresponding photoelectron spectra. In addition, theoretical results
      are presented that take the core-hole orientation of the various spin-orbit-split
      and molecular-field-split S 2p(-1) states into account. Auger transitions to
      eight metastable dicationic final states are observed and assigned on the basis
      of the theoretical results. From Franck-Condon analysis, assuming Morse
      potentials along the normal coordinates for seven of the observed quasi-stable
      dicationic final states, information on the potential-energy surfaces is derived
      and compared with theoretical results from the literature.

PMID- 22852622
TI  - Quantitative investigations of aggregate systems.
AB  - Nanomaterials with disordered, ramified structure are increasingly being used for
      applications where low cost and enhanced performance are desired. A particular
      example is the use in printed electronics of inorganic conducting and
      semiconducting nanoparticles. The electrical, as well as other physical
      properties depend on the arrangement and connectivity of the particles in such
      aggregate systems. Quantification of aggregate structure and development of
      structure/property relationships is difficult and progress in the application of
      these materials in electronics has mainly been empirical. In this paper, a
      scaling model is used to parameterize the structure of printed electronic layers.
      This model has chiefly been applied to polymers but surprisingly it shows
      applicability to these nanolayers. Disordered structures of silicon nanoparticles
      forming aggregates are investigated using small angle x-ray scattering coupled
      with the scaling model. It is expected that predictions using these structural
      parameters can be made for electrical properties. The approach may have wide use
      in understanding and designing nano-aggregates for electronic devices.

PMID- 22852623
TI  - Gas phase hyper-Rayleigh scattering measurements.
AB  - Measurements of hyper-Rayleigh scattering intensities and polarization ratios are
      presented for nine small molecules in the gas phase [CH(4), CF(4), CCl(4), N(2)O,
      NH(3), D(2)O, SO(2), CF(2)Cl(2), and (CH(3))(2)CO]. In four cases [CH(4), CF(4),
      CCl(4), and N(2)O] all molecular hyperpolarizability tensor components can be
      determined from the measurements. The results of this experiment are compared
      with the results of previous ab initio calculations, finding discrepancies up to
      60%. Including vibrational contributions decreases the discrepancies for CH(4)
      and CF(4) and increases them for CCl(4), D(2)O, and NH(3).

PMID- 22852624
TI  - Effect of molecular rotation on enantioseparation.
AB  - Recently, several laser schemes have been proposed to separate racemic mixtures
      of enantiomers by splitting a molecular beam into subbeams consisting of
      molecules of definite chirality [Y. Li, C. Bruder, and C. P. Sun, Phys. Rev.
      Lett. 99, 130403 (2007); X. Li and M. Shapiro, J. Chem. Phys. 132, 194315
      (2010)]. These ideas rely on laser-induced effective gauge potentials in an
      adiabatic basis which lead to a chirality dependent force on the center-of-mass.
      However, the effect of molecular rotation has been neglected in these studies.
      Accounting for the full molecular quantum state we find that the potentials from
      the adiabatic dressed state approach cannot be recovered once the molecular
      orientation dynamics is included, even in the rotational ground state. This
      affects substantially the ability to perform enantioseparation in the above
      mentioned setups.

PMID- 22852625
TI  - Local atomic structure in equilibrium and supercooled liquid Zr(75.5)Pd(24.5).
AB  - Atomic structures were obtained in equilibrium and supercooled eutectic
      Zr(75.5)Pd(24.5) liquids by in situ high-energy synchrotron diffraction
      measurements using the beamline electrostatic levitation (BESL) technique, which
      provides a high-vacuum, containerless, environment. Reverse Monte Carlo fits to
      the x-ray static structure factors, constrained using partial pair correlation
      functions obtained from ab initio molecular dynamics simulations, indicate the
      presence of medium-range order (MRO) in the form of a strong tendency for Pd-Pd
      (solute-solute) avoidance. This order persists over the entire temperature range
      studied, from 170  degrees C above the equilibrium liquidus temperature to 263 
      degrees C below it. Further, a quantitative analysis of the atomic structures
      obtained indicates a modest degree of icosahedral-like local order around Pd
      atoms, with the clusters showing an increased tendency for face-sharing to form
      more extended structures with decreasing temperature.

PMID- 22852626
TI  - Quasi-harmonic approximation of thermodynamic properties of ice Ih, II, and III.
AB  - Several thermodynamic properties of ice Ih, II, and III are studied by a quasi
      harmonic approximation and compared to results of quantum path integral and
      classical simulations. This approximation allows to obtain thermodynamic
      information at a fraction of the computational cost of standard simulation
      methods, and at the same time permits studying quantum effects related to zero
      point vibrations of the atoms. Specifically, we have studied the crystal volume,
      bulk modulus, kinetic energy, enthalpy, and heat capacity of the three ice phases
      as a function of temperature and pressure. The flexible q-TIP4P/F model of water
      was employed for this study, although the results concerning the capability of
      the quasi-harmonic approximation are expected to be valid independently of the
      employed water model. The quasi-harmonic approximation reproduces with reasonable
      accuracy the results of quantum and classical simulations showing an improved
      agreement at low temperatures (T< 100 K). This agreement does not deteriorate as
      a function of pressure as long as it is not too close to the limit of mechanical
      stability of the ice phases.

PMID- 22852627
TI  - Structure and dynamics of water in nonionic reverse micelles: a combined time
      resolved infrared and small angle x-ray scattering study.
AB  - We study the structure and reorientation dynamics of nanometer-sized water
      droplets inside nonionic reverse micelles (water/Igepal-CO-520/cyclohexane) with
      time-resolved mid-infrared pump-probe spectroscopy and small angle x-ray
      scattering. In the time-resolved experiments, we probe the vibrational and
      orientational dynamics of the O-D bonds of dilute HDO:H(2)O mixtures in Igepal
      reverse micelles as a function of temperature and micelle size. We find that even
      small micelles contain a large fraction of water that reorients at the same rate
      as water in the bulk, which indicates that the polyethylene oxide chains of the
      surfactant do not penetrate into the water volume. We also observe that the
      confinement affects the reorientation dynamics of only the first hydration layer.
      From the temperature dependent surface-water dynamics, we estimate an activation
      enthalpy for reorientation of 45 +/- 9 kJ mol(-1) (11 +/- 2 kcal mol(-1)), which
      is close to the activation energy of the reorientation of water molecules in ice.

PMID- 22852628
TI  - Investigation of the hydrogen bonding in ice Ih by first-principles density
      function methods.
AB  - It is a well recognized difficult task to simulate the vibrational dynamics of
      ices using the density functional theory (DFT), and there has thus been rather
      limited success in modelling the inelastic neutron scattering (INS) spectra for
      even the simplest structure of ice, ice Ih, particularly in the translational
      region below 400 cm(-1). The reason is partly due to the complex nature of
      hydrogen bonding (H-bond) among water-water molecules which require considerable
      improvement of the quantum mechanical simulation methods, and partly owing to the
      randomness of protons in ice structures which often requires simulation of large
      super-lattices. In this report, we present the first series of successful
      simulation results for ice Ih using DFT methods. On the basis of the recent
      advancement in the DFT programs, we have achieved for the first time theoretical
      outcomes that not only reproduce the rotational frequencies between 500 to 1200
      cm(-1) for ice Ih, but also the two optic peaks at ~240 and 320 cm(-1) in the
      translational region of the INS spectra [J. C. Li, J. Chem. Phys 105, 6733
      (1996)]. Besides, we have also investigated the impact of pairwise configurations
      of H(2)O molecules on the H-bond and found that different proton arrangements of
      pairwise H(2)O in the ice Ih crystal lattice could not alter the nature of H-bond
      as significantly as suggested in an early paper [J. C. Li and D. K. Ross, Nature
      (London) 365, 327 (1993)], i.e., reproducing the two experimental optic peaks do
      not need to invoke the two H-bonds as proposed in the previous model which led to
      considerable debates. The results of this work suggest that the observed optic
      peaks may be attributed to the coupling between the two bands of H-O stretching
      modes in H(2)O. The current computational work is expected to shed new light on
      the nature of the H-bonds in water, and in addition to offer a new approach
      towards probing the interaction between water and biomaterials for which H-bond
      is essential.

PMID- 22852629
TI  - Dynamical simulation of dipolar Janus colloids: equilibrium structure and
      thermodynamics.
AB  - The static microstructures and thermodynamics of a colloidal dispersion of
      dipolar Janus (DJ) particles-that is, dipolar spheres in which each hemisphere is
      specified by a different charge interaction-have been investigated through
      simulation. DJ particles are modeled at a high level of detail with pairwise
      potentials represented as a sum of a spherically symmetric soft repulsion and an
      orientation-dependent electrostatic component using continuous potentials. The
      latter is important because it allows for the use of conventional molecular
      dynamics simulations, and is in contrast to the patch model and dipolar hard
      sphere model, which are discontinuous and therefore do not. The electrostatics
      are represented through a rigorous pointwise (PW) covering of two different
      hemispheres filled by points of corresponding charge. An isotropic coarse
      graining (CG) of the PW models serves as a limit of the structure wherein the
      orientations of the DJ particles can be pairwise averaged. Over the range of
      volume fractions and DJ charge densities studied-consistent with reversible
      structures absent of long-range correlations-the CG model agrees well with the PW
      model with respect to equilibrium structure (isotropic pair correlation) and
      ensemble free energy. Time-dependent relaxation simulations of the PW model
      suggest that chain structures are not expected in liquid phases in contrast to
      that which has been observed for point dipole models of simple polar fluids.

PMID- 22852630
TI  - Ab initio molecular dynamics study of water at constant pressure using converged
      basis sets and empirical dispersion corrections.
AB  - It is generally believed that studies of liquid water using the generalized
      gradient approximation to density functional theory require dispersion
      corrections in order to obtain reasonably accurate structural and dynamical
      properties. Here, we report on an ab initio molecular dynamics study of water in
      the isothermal-isobaric ensemble using a converged discrete variable
      representation basis set and an empirical dispersion correction due to Grimme [J.
      Comp. Chem. 27, 1787 (2006)]. At 300 K and an applied pressure of 1 bar, the
      density obtained without dispersion corrections is approximately 0.92 g/cm(3)
      while that obtained with dispersion corrections is 1.07 g/cm(3), indicating that
      the empirical dispersion correction overestimates the density by almost as much
      as it is underestimated without the correction for this converged basis. Radial
      distribution functions exhibit a loss of structure in the second solvation shell.
      Comparison of our results with other studies using the same empirical correction
      suggests the cause of the discrepancy: the Grimme dispersion correction is
      parameterized for use with a particular basis set; this parameterization is
      sensitive to this choice and, therefore, is not transferable to other basis sets.

PMID- 22852631
TI  - Phase diagram of hard snowman-shaped particles.
AB  - We present the phase diagram of hard snowman-shaped particles calculated using
      Monte Carlo simulations and free energy calculations. The snowman particles
      consist of two hard spheres rigidly attached at their surfaces. We find a rich
      phase behavior with isotropic, plastic crystal, and aperiodic crystal phases. The
      crystalline phases found to be stable for a given sphere diameter ratio
      correspond mostly to the close packed structures predicted for equimolar binary
      hard-sphere mixtures of the same diameter ratio. However, our results also show
      several crystal-crystal phase transitions, with structures with a higher degree
      of degeneracy found to be stable at lower densities, while those with the best
      packing are found to be stable at higher densities.

PMID- 22852632
TI  - Transport properties of room-temperature ionic liquids from classical molecular
      dynamics.
AB  - Room-temperature ionic liquids (RTILs) have attracted much attention in the
      scientific community in the past decade due their novel and highly customizable
      properties. Nonetheless, their high viscosities pose serious limitations to the
      use of RTILs in practical applications. To elucidate some of the physical aspects
      behind transport properties of RTILs, extensive classical molecular dynamics
      calculations are reported. Here, in particular, bulk viscosities and ionic
      conductivities of butyl-methyl-imidazole based RTILs are presented over a wide
      range of temperatures. The dependence of the properties of the liquids on
      simulation parameters, e.g., system-size effects or the choice of the interaction
      potential, is analyzed in detail.

PMID- 22852633
TI  - Phase diagram of supercooled water confined to hydrophilic nanopores.
AB  - We present a phase diagram for water confined to cylindrical silica nanopores in
      terms of pressure, temperature, and pore radius. The confining cylindrical wall
      is hydrophilic and disordered, which has a destabilizing effect on ordered water
      structure. The phase diagram for this class of systems is derived from general
      arguments, with parameters taken from experimental observations and computer
      simulations and with assumptions tested by computer simulation. Phase space
      divides into three regions: a single liquid, a crystal-like solid, and glass. For
      large pores, radii exceeding 1 nm, water exhibits liquid and crystal-like
      behaviors, with abrupt crossovers between these regimes. For small pore radii,
      crystal-like behavior is unstable and water remains amorphous for all non-zero
      temperatures. At low enough temperatures, these states are glasses. Several
      experimental results for supercooled water can be understood in terms of the
      phase diagram we present.

PMID- 22852634
TI  - Structural, vibrational, and thermal properties of densified silicates: insights
      from molecular dynamics.
AB  - Structural, vibrational, and thermal properties of densified sodium silicate
      (close to NS2) are investigated with classical molecular dynamics simulations of
      the glass and the liquid state. A systematic investigation of the glass structure
      with respect to density was performed. We observe a repolymerization of the
      network manifested by a transition from a tetrahedral to an octahedral silicon
      environment, the decrease of the amount of non-bridging oxygen atoms and the
      appearance of threefold coordinated oxygen atoms (triclusters). Anomalous changes
      in the medium range order are observed, the first sharp diffraction peak showing
      a minimum of its full-width at half maximum according to density. Generic
      vibrational trends are observed, such as the shift of the Boson peak intensity to
      higher frequencies and the decrease of its intensity. Finally, we show that the
      thermal behavior of the liquid can be reproduced by the Birch-Murnaghan equation
      of states, thus allowing us to compute the isothermal compressibility.

PMID- 22852635
TI  - The effects of charge transfer on the aqueous solvation of ions.
AB  - Ab initio-based charge partitioning of ionic systems results in ions with non
      integer charges. This charge-transfer (CT) effect alters both short- and long
      range interactions. Until recently, the effects of CT have been mostly neglected
      in molecular dynamics (MD) simulations. The method presented in this paper for
      including charge transfer between ions and water is consistent with ab initio
      charge partitioning and does not add significant time to the simulation. The ions
      of sodium, potassium, and chloride are parameterized to reproduce dimer
      properties and aqueous structures. The average charges of the ions from MD
      simulations (0.900, 0.919, and -0.775 for Na(+), K(+), and Cl(-), respectively)
      are consistent with quantum calculations. The hydration free energies calculated
      for these ions are in agreement with experimental estimates, which shows that the
      interactions are described accurately. The ions also have diffusion constants in
      good agreement with experiment. Inclusion of CT results in interesting properties
      for the waters in the first solvation shell of the ions. For all ions studied,
      the first shell waters acquire a partial negative charge, due to the difference
      between water-water and water-ion charge-transfer amounts. CT also reduces
      asymmetry in the solvation shell of the chloride anion, which could have
      important consequences for the behavior of chloride near the air-water interface.

PMID- 22852637
TI  - Molecular vibrations-induced quantum beats in two-dimensional electronic
      spectroscopy.
AB  - Quantum beats in nonlinear spectroscopy of molecular aggregates are often
      attributed to electronic phenomena of excitonic systems, while nuclear degrees of
      freedom are commonly included into models as overdamped oscillations of bath
      constituents responsible for dephasing. However, molecular systems are coupled to
      various high-frequency molecular vibrations, which can cause the spectral beats
      hardly distinguishable from those created by purely electronic coherences. Models
      containing damped, undamped, and overdamped vibrational modes coupled to an
      electronic molecular transition are discussed in this paper in context of linear
      absorption and two-dimensional electronic spectroscopy. Analysis of different
      types of bath models demonstrates how do vibrations map onto two-dimensional
      spectra and how the damping strength of the coherent vibrational modes can be
      resolved from spectroscopic signals.

PMID- 22852636
TI  - 1H relaxation dispersion in solutions of nitroxide radicals: effects of hyperfine
      interactions with 14N and 15N nuclei.
AB  - (1)H relaxation dispersion of decalin and glycerol solutions of nitroxide
      radicals, 4-oxo-TEMPO-d(16)-(15)N and 4-oxo-TEMPO-d(16)-(14)N was measured in the
      frequency range of 10 kHz-20 MHz (for (1)H) using STELAR Field Cycling
      spectrometer. The purpose of the studies is to reveal how the spin dynamics of
      the free electron of the nitroxide radical affects the proton spin relaxation of
      the solvent molecules, depending on dynamical properties of the solvent.
      Combining the results for both solvents, the range of translational diffusion
      coefficients, 10(-9)-10(-11) m(2)/s, was covered (these values refer to the
      relative diffusion of the solvent and solute molecules). The data were analyzed
      in terms of relaxation formulas including the isotropic part of the electron spin
      - nitrogen spin hyperfine coupling (for the case of (14)N and (15)N) and
      therefore valid for an arbitrary magnetic field. The influence of the hyperfine
      coupling on (1)H relaxation of solvent molecules depending on frequency and time
      scale of the translational dynamics was discussed in detail. Special attention
      was given to the effect of isotope substitution ((14)N/(15)N). In parallel, the
      influence of rotational dynamics on the inter-molecular (radical - solvent)
      electron spin - proton spin dipole-dipole coupling (which is the relaxation
      mechanism of solvent protons) was investigated. The rotational dynamics is of
      importance as the interacting spins are not placed in the molecular centers. It
      was demonstrated that the role of the isotropic hyperfine coupling increases for
      slower dynamics, but it is of importance already in the fast motion range (10(
      9)m(2)/s). The isotope effects is small, however clearly visible; the (1)H
      relaxation rate for the case of (15)N is larger (in the range of lower
      frequencies) than for (14)N. It was shown that when the diffusion coefficient
      decreases below 5 * 10(-11) m(2)/s electron spin relaxation becomes of importance
      and its role becomes progressively more significant when the dynamics slows done.
      As far as the influence of the rotational dynamics is concerned, it was show that
      this process is of importance not only in the range of higher frequencies (like
      for diamagnetic solutions) but also at low and intermediate frequencies.

PMID- 22852638
TI  - Electronic structures of the SrTiO3(110) surface in different reconstructions.
AB  - The surface of SrTiO(3)(110) single crystal is prepared in monophase with
      different reconstructions. The increase of surface Ti concentration is
      responsible for the evolution of the reconstruction from (4*1) to (2*8), and to a
      new (1*10) structure. It also induces the enhancement of the surface metallicity,
      characterized by the appearance of the in-gap states and the increasing Drude
      weight as measured by the electron and photoelectron spectroscopies. We attribute
      the metallicity to the reduced Ti ions, which is consistent with the observed
      band structures and the shift of the phonon energy. It is indicated that a
      heterointerface between a reduced titanate layer and SrTiO(3) crystal with unique
      electronic structure can be obtained by the simple treatment.

PMID- 22852639
TI  - Evidence for phase separation of ethanol-water mixtures at the hydrogen
      terminated nanocrystalline diamond surface.
AB  - Interactions between ethanol-water mixtures and a hydrophobic hydrogen terminated
      nanocrystalline diamond surface, are investigated by sessile drop contact angle
      measurements. The surface free energy of the hydrophobic surface, obtained with
      pure liquids, differs strongly from values obtained by ethanol-water mixtures.
      Here, a model which explains this difference is presented. The model suggests
      that, due to a higher affinity of ethanol for the hydrophobic surface, when
      compared to water, a phase separation occurs when a mixture of both liquids is in
      contact with the H-terminated diamond surface. These results are supported by a
      computational study giving insight in the affinity and related interaction at the
      liquid-solid interface.

PMID- 22852640
TI  - Interfacial properties of free-standing poly(3-hexylthiophene) films.
AB  - Using full atomistic classical molecular dynamics simulations, the interfacial
      properties of free-standing poly(3-hexylthiophene) (P3HT) films have been
      investigated. The orientations of different parts of the P3HT chain and the
      surface tensions of the films were calculated in a temperature range of 540 K-600
      K. At the liquid/vacuum interface, the P3HT chain shows ordering by exposing
      hexyl groups at the interface, while the chain backbone lays flat with the
      thiophene ring preferentially tilt toward the surface. At the interface, the
      terminal methyl groups of hexyl side chains are in excess compared to the
      methylene groups or thiophene rings. The surface tension of P3HT in its melt
      state shows similar temperature dependence to that of polymers that have long
      alkyl side chains. The surface tension values are comparable to those polymers
      that expose methyl or methylene groups on the surface. The surface tension values
      determined for the melt state are lower than the experimental reported values for
      crystalline P3HT films, as expected.

PMID- 22852641
TI  - Restricted diffusion in NMR in arbitrary inhomogeneous magnetic fields and an
      application to circular layers.
AB  - The multiple correlation function technique is a versatile approach for the
      computation of the nuclear magnetic resonance (NMR) magnetization of spins
      diffusing in inhomogeneous fields. The difficulties in deriving the required
      interaction matrices are one of the main limitations of this technique. In this
      work, methods to compute the interaction matrices of general magnetic field
      profiles from those of linear fields by basic matrix manipulations are presented.
      As an example, susceptibility induced magnetic field profiles that are generated
      by cylindrical capillaries residing in homogeneous magnetic fields are
      considered.

PMID- 22852642
TI  - Many competing ceria (110) oxygen vacancy structures: from small to large
      supercells.
AB  - We present periodic "DFT+U" studies of single oxygen vacancies on the CeO(2)(110)
      surface using a number of different supercells, finding a range of different
      local minimum structures for the vacancy and its two accompanying Ce(III) ions.
      We find three different geometrical structures in combination with a variety of
      different Ce(III) localization patterns, several of which have not been studied
      before. The desired trapping of electrons was achieved in a two-stage
      optimization procedure. We find that the surface oxygen nearest to the vacancy
      either moves within the plane towards the vacancy, or rises out of the surface
      into either a symmetric or an unsymmetric bridge structure. Results are shown in
      seven slab geometry supercells, p(2 * 1), p(2 * 2), p(2 * 3), p(3 * 2), p(2 * 4),
      p(4 * 2), and p(3 * 3), and indicate that the choice of supercell can affect the
      results qualitatively and quantitatively. An unsymmetric bridge structure with
      one nearest and one next-nearest neighbour Ce(III) ion (a combination of
      localizations not previously found) is the ground state in all (but one) of the
      supercells studied here, and the relative stability of other structures depends
      strongly on supercell size. Within any one supercell the formation energies of
      the different vacancy structures differ by up to 0.5 eV, but the same structure
      can vary by up to ~1 eV between supercells. Furthermore, finite size scaling
      suggests that the remaining errors (compared to still larger supercells) can also
      be ~1 eV for some vacancy structures.

PMID- 22852643
TI  - Random sequential adsorption on fractals.
AB  - Irreversible adsorption of spheres on flat collectors having dimension d < 2 is
      studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals
      (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled
      numerically using random sequential adsorption (RSA) algorithm. The paper
      concentrates on measurement of fundamental properties of coverages, i.e., maximal
      random coverage ratio and density autocorrelation function, as well as RSA
      kinetics. Obtained results allow to improve phenomenological relation between
      maximal random coverage ratio and collector dimension. Moreover, simulations show
      that, in general, most of known dimensional properties of adsorbed monolayers are
      valid for non-integer dimensions.

PMID- 22852644
TI  - Wall-liquid and wall-crystal interfacial free energies via thermodynamic
      integration: a molecular dynamics simulation study.
AB  - A method is proposed to compute the interfacial free energy of a Lennard-Jones
      system in contact with a structured wall by molecular dynamics simulation. Both
      the bulk liquid and bulk face-centered-cubic crystal phase along the (111)
      orientation are considered. Our approach is based on a thermodynamic integration
      scheme where first the bulk Lennard-Jones system is reversibly transformed to a
      state where it interacts with a structureless flat wall. In a second step, the
      flat structureless wall is reversibly transformed into an atomistic wall with
      crystalline structure. The dependence of the interfacial free energy on various
      parameters such as the wall potential, the density and orientation of the wall is
      investigated. The conditions are indicated under which a Lennard-Jones crystal
      partially wets a flat wall.

PMID- 22852645
TI  - Potassium-intercalated H2Pc films: alkali-induced electronic and geometrical
      modifications.
AB  - X-ray spectroscopy studies of potassium intercalated metal-free phthalocyanine
      multilayers adsorbed on Al(110) have been undertaken. Photoelectron spectroscopy
      measurements show the presence of several charge states of the molecules upon K
      intercalation, due to a charge transfer from the alkali. In addition, the
      comparison of valence band photoemission spectra with the density functional
      theory calculations of the density of states of the H(2)Pc(-) anion indicates a
      filling of the formerly lowest unoccupied molecular orbital by charge transfer
      from the alkali. This is further confirmed by x-ray absorption spectroscopy (XAS)
      studies, which show a decreased density of unoccupied states. XAS measurements in
      different experimental geometries reveal that the molecules in the pristine film
      are standing upright on the surface or are only slightly tilted away from the
      surface normal but upon K intercalation, the molecular orientation is changed in
      that the tilt angle of the molecules increases.

PMID- 22852646
TI  - Entropy of single-file water in (6,6) carbon nanotubes.
AB  - We used molecular dynamics simulations to investigate the thermodynamics of
      filling of a (6,6) open carbon nanotube (diameter D = 0.806 nm) solvated in TIP3P
      water over a temperature range from 280 K to 320 K at atmospheric pressure. In
      simulations of tubes with slightly weakened carbon-water attractive interactions,
      we observed multiple filling and emptying events. From the water occupancy
      statistics, we directly obtained the free energy of filling, and from its
      temperature dependence the entropy of filling. We found a negative entropy of
      about -1.3 k(B) per molecule for filling the nanotube with a hydrogen-bonded
      single-file chain of water molecules. The entropy of filling is nearly
      independent of the strength of the attractive carbon-water interactions over the
      range studied. In contrast, the energy of transfer depends strongly on the carbon
      water attraction strength. These results are in good agreement with entropies of
      about -0.5 k(B) per water molecule obtained from grand-canonical Monte Carlo
      calculations of water in quasi-infinite tubes in vacuum under periodic boundary
      conditions. Overall, for realistic carbon-water interactions we expect that at
      ambient conditions filling of a (6,6) carbon nanotube open to a water reservoir
      is driven by a favorable decrease in energy, and opposed by a small loss of water
      entropy.

PMID- 22852647
TI  - Pt3 and Pt4 clusters on graphene monolayers supported on a Ni(111) substrate:
      relativistic density-functional calculations.
AB  - Density-functional theory including spin-orbit coupling and corrections for
      dispersion forces has been used to investigate the structural and magnetic
      properties of Pt(3) and Pt(4) clusters deposited on a graphene layer supported on
      a Ni(111) substrate. It is shown that the strong interaction of the Pt atoms with
      the Ni-supported graphene stabilizes a flat triangular and a slightly bent
      rhombic structure of the clusters. Pt atoms are located nearly on top of the C
      atoms of the graphene layer, slightly shifted towards the bridge positions
      because the Pt-Pt distances are larger than the C-C distances of the graphene
      sheet lattice-matched to the Ni support. The strong interaction with the
      substrate leads to a substantial reduction of both the spin and orbital moments
      of the Pt atoms, not only compared to the clusters in the gas-phase, but also
      compared to those adsorbed on a freestanding graphene layer. The trends in the
      magnetic moments and in the magnetic anisotropy of the cluster/substrate complex
      have been analyzed and it is demonstrated that the anisotropy is dominated by the
      Ni support.

PMID- 22852648
TI  - A study of the anisotropy of stress in a fluid confined in a nanochannel.
AB  - We present molecular dynamics simulations of planar Poiseuille flow of a Lennard
      Jones fluid at various temperatures and body forces. Local thermostatting is used
      close to the walls to reach steady-state up to a limit body force. Macroscopic
      fields are obtained from microscopic data by time- and space-averaging and
      smoothing the data with a self-consistent coarse-graining method based on kernel
      interpolation. Two phenomena make the system interesting: (i) strongly confined
      fluids show layering, i.e., strong oscillations in density near the walls, and
      (ii) the stress deviates from the Newtonian fluid assumption, not only in the
      layered regime, but also much further away from the walls. Various scalar,
      vectorial, and tensorial fields are analyzed and related to each other in order
      to understand better the effects of both the inhomogeneous density and the
      anisotropy on the flow behavior and rheology. The eigenvalues and eigendirections
      of the stress tensor are used to quantify the anisotropy in stress and form the
      basis of a newly proposed objective, inherently anisotropic constitutive model
      that allows for non-collinear stress and strain gradient by construction.

PMID- 22852649
TI  - Quantitative description of the self-assembly of patchy particles into chains and
      rings.
AB  - We numerically study a simple fluid composed of particles having a hard-core
      repulsion complemented by two patchy attractive sites on the particle poles. An
      appropriate choice of the patch angular width allows for the formation of ring
      structures which, at low temperatures and low densities, compete with the growth
      of linear aggregates. The simplicity of the model makes it possible to compare
      simulation results and theoretical predictions based on the Wertheim perturbation
      theory, specialized to the case in which ring formation is allowed. Such a
      comparison offers a unique framework for establishing the quality of the analytic
      predictions. We find that the Wertheim theory describes remarkably well the
      simulation results.

PMID- 22852650
TI  - Micellization and relaxation in solution with spherical micelles via the discrete
      Becker-Doring equations at different total surfactant concentrations.
AB  - A numerical description of micellization and relaxation to an aggregate
      equilibrium in surfactant solution with nonionic spherical micelles has been
      developed on the basis of a discrete form of the Becker-Doring kinetic equations.
      Two different models for the monomer-aggregate attachment-detachment rates have
      been used, and it has been shown that the results are qualitatively the same. The
      full discrete spectrum of characteristic times of micellar relaxation and first
      relaxation modes in their dependence on equilibrium monomer concentration have
      been found with using the linearized form of the Becker-Doring kinetic equations.
      Overall time behavior of surfactant monomer and aggregate concentrations in
      micellization and relaxation at large initial deviations from final equilibrium
      has been studied with the help of nonlinearized discrete Becker-Doring kinetic
      equations. Comparison of the computed results with the analytical ones known in
      the limiting cases from solutions of the linearized and nonlinearized continuous
      Becker-Doring kinetic equation demonstrates general agreement.

PMID- 22852651
TI  - Trapping in dendrimers and regular hyperbranched polymers.
AB  - Dendrimers and regular hyperbranched polymers are two classic families of
      macromolecules, which can be modeled by Cayley trees and Vicsek fractals,
      respectively. In this paper, we study the trapping problem in Cayley trees and
      Vicsek fractals with different underlying geometries, focusing on a particular
      case with a perfect trap located at the central node. For both networks, we
      derive the exact analytic formulas in terms of the network size for the average
      trapping time (ATT)-the average of node-to-trap mean first-passage time over the
      whole networks. The obtained closed-form solutions show that for both Cayley
      trees and Vicsek fractals, the ATT display quite different scalings with various
      system sizes, which implies that the underlying structure plays a key role on the
      efficiency of trapping in polymer networks. Moreover, the dissimilar scalings of
      ATT may allow to differentiate readily between dendrimers and hyperbranched
      polymers.

PMID- 22852652
TI  - Entropic stochastic resonance of a flexible polymer chain in a confined system.
AB  - We have studied the dynamics of a flexible polymer chain in constrained dumb-bell
      shape geometry subject to a periodic force and external noise along the
      longitudinal direction. It is found that the system exhibits a feature of
      entropic stochastic resonance (ESR), i.e., the temporal coherence of the polymer
      motion can reach a maximum level for an optimal noise intensity. We demonstrate
      that the occurrence of ESR is robust to the change of chain length, while the
      bottleneck width should be properly chosen. A gravity force in the vertical
      direction is not necessary for the ESR here, however, the elastic coupling
      between polymer beads is crucial.

PMID- 22852654
TI  - An analytical approximation for the orientation-dependent excluded volume of
      tangent hard sphere chains of arbitrary chain length and flexibility.
AB  - Onsager-like theories are commonly used to describe the phase behavior of nematic
      (only orientationally ordered) liquid crystals. A key ingredient in such theories
      is the orientation-dependent excluded volume of two molecules. Although for hard
      convex molecular models this is generally known in analytical form, for more
      realistic molecular models that incorporate intramolecular flexibility, one has
      to rely on approximations or on computationally expensive Monte Carlo techniques.
      In this work, we provide a general correlation for the excluded volume of tangent
      hard-sphere chains of arbitrary chain length and flexibility. The flexibility is
      introduced by means of the rod-coil model. The resulting correlation is of simple
      analytical form and accurately covers a wide range of pure component excluded
      volume data obtained from Monte Carlo simulations of two-chain molecules. The
      extension to mixtures follows naturally by applying simple combining rules for
      the parameters involved. The results for mixtures are also in good agreement with
      data from Monte Carlo simulations. We have expressed the excluded volume as a
      second order power series in sin (gamma), where gamma is the angle between the
      molecular axes. Such a representation is appealing since the solution of the
      Onsager Helmholtz energy functional usually involves an expansion of the excluded
      volume in Legendre coefficients. Both for pure components and mixtures, the
      correlation reduces to an exact expression in the limit of completely linear
      chains. The expression for mixtures, as derived in this work, is thereby an exact
      extension of the pure component result of Williamson and Jackson [Mol. Phys. 86,
      819-836 (1995)].

PMID- 22852655
TI  - Atomistic picture of isothermal volume relaxation behavior of atactic polystyrene
      glass provided by a molecular dynamics simulation.
AB  - Using an atomistic molecular dynamics (MD) simulation, we study the volume
      relaxation behavior of atactic polystyrene and attempt to correlate this
      macroscopic behavior with certain microscopic aspects. To this end, the gyration
      radius, the dimensionless relative shape anisotropy, the mean-squared
      displacement, and the non-Gaussian parameter are examined simultaneously. Our
      result shows that the structures characterized at different length scales change
      in a self-similar way and these changes are intimately correlated to the
      translational mobility of atoms. The initial incubation of structural changes at
      the different scales originates from the restriction of mobility due to the cage
      effect. The applicability of the MD simulation to the investigation of the bulk
      properties is discussed.

PMID- 22852653
TI  - Density functional theory for encapsidated polyelectrolytes: a comparison with
      Monte Carlo simulation.
AB  - Genome packaging inside viral capsids is strongly influenced by the molecular
      size and the backbone structure of RNA/DNA chains and their electrostatic
      affinity with the capsid proteins. Coarse-grained models are able to capture the
      generic features of non-specific interactions and provide a useful testing ground
      for theoretical developments. In this work, we use the classical density
      functional theory (DFT) within the framework of an extended primitive model for
      electrolyte solutions to investigate the self-organization of flexible and semi
      flexible linear polyelectrolytes in spherical capsids that are permeable to small
      ions but not polymer segments. We compare the DFT predictions with Monte Carlo
      (MC) simulation for the density distributions of polymer segments and small ions
      at different backbone flexibilities and several solution conditions. In general,
      the agreement between DFT and MC is near quantitative except when the simulation
      results are noticeably influenced by the boundary effects. The numerical
      efficiency of the DFT calculations makes it promising as a useful tool for
      quantification of the structural and thermodynamic properties of viral
      nucleocapsids in vivo and at conditions pertinent to experiments.

PMID- 22852656
TI  - Strong stretching theory for diblock copolymers in thin films under application
      of electric fields.
AB  - We investigate the microphases of asymmetric AB diblock copolymers confined to
      thin films in the strong segregation limit under the application of electric
      fields. We evaluate the free energy of a given set of possible phases and present
      phase diagrams for diblock copolymers with a cylindrical bulk phase in dependence
      of the film thickness and the attraction between the confining walls and the A or
      B monomers. This is done for different field strengths and volume fractions. We
      find that with increasing field strength structures show a preference for
      alignment with the field. The alignment is stronger when the permittivity of the
      minority monomer is larger than that of the majority monomer. Depending on the
      strength of the wall potential and the film thickness, the walls can become
      completely wetted by the minority monomer.

PMID- 22852657
TI  - Low energy electron induced damage to plasmid DNA pQE30.
AB  - Low energy electrons (LEEs) are produced in copious amounts by the primary
      radiation used in radiation therapy. The damage caused to the DNA by these
      secondary electrons in the energy range 5-22 eV has been studied to understand
      their possible role in radiation induced damage. Electrons are irradiated on
      dried films of plasmid DNA (pQE30) and analysed using agarose gel
      electrophoresis. Single strand breaks (SSBs) induced by LEE to supercoiled
      plasmid DNA show resonance structures at 7, 12, and 15 eV for low doses and 6,
      10, and ~18 eV at saturation doses. The present measurements have an overall
      agreement with the literature that LEEs resonantly induce SSBs in DNA. Resonant
      peaks in the SSBs induced by LEEs at 7, 12, and 15 eV with the lowest employed
      dose in the current study are somewhat different from those reported earlier by
      two groups. The observed differences are perhaps related to the irradiation dose,
      conditions and the nature of DNA employed, which is further elaborated.

PMID- 22852658
TI  - Single-molecule enzyme kinetics in the presence of inhibitors.
AB  - Recent studies in single-molecule enzyme kinetics reveal that the turnover
      statistics of a single enzyme is governed by the waiting time distribution that
      decays as mono-exponential at low substrate concentration and multi-exponential
      at high substrate concentration. The multi-exponentiality arises due to protein
      conformational fluctuations, which act on the time scale longer than or
      comparable to the catalytic reaction step, thereby inducing temporal fluctuations
      in the catalytic rate resulting in dynamic disorder. In this work, we study the
      turnover statistics of a single enzyme in the presence of inhibitors to show that
      the multi-exponentiality in the waiting time distribution can arise even when
      protein conformational fluctuations do not influence the catalytic rate. From the
      Michaelis-Menten mechanism of inhibited enzymes, we derive exact expressions for
      the waiting time distribution for competitive, uncompetitive, and mixed
      inhibitions to quantitatively show that the presence of inhibitors can induce
      dynamic disorder in all three modes of inhibitions resulting in temporal
      fluctuations in the reaction rate. In the presence of inhibitors, dynamic
      disorder arises due to transitions between active and inhibited states of
      enzymes, which occur on time scale longer than or comparable to the catalytic
      step. In this limit, the randomness parameter (dimensionless variance) is greater
      than unity indicating the presence of dynamic disorder in all three modes of
      inhibitions. In the opposite limit, when the time scale of the catalytic step is
      longer than the time scale of transitions between active and inhibited enzymatic
      states, the randomness parameter is unity, implying no dynamic disorder in the
      reaction pathway.

PMID- 22852659
TI  - Canonical and micro-canonical analysis of folding of trpzip2: an all-atom replica
      exchange Monte Carlo simulation study.
AB  - The density of states of trpzip2, a beta-hairpin peptide, has been explored at
      all-atom level. Replica exchange Monte Carlo method was used for sufficient
      sampling over a wide range of temperature. Micro-canonical analysis was performed
      to confirm that the phase transition behavior of this two-state folder is first
      order-like. Canonical analysis of heat capacity suggests that hydrogen bonding
      interaction exerts a considerable positive influence on folding cooperativity, in
      contrast, hydrophobic interaction is insufficient for high degree of folding
      cooperativity. Furthermore, we explain physical nature of the folding process
      from free energy landscape perspective and extensively analyse hydrogen bonding
      and stacking energy.

PMID- 22852660
TI  - Note: accounting for pressure effects on the calculated equilibrium structure of
      glassy GeSe2.

PMID- 22852664
TI  - Invited review article: technology for attosecond science.
AB  - We describe a complete technological system at Imperial College London for
      Attosecond Science studies. The system comprises a few-cycle, carrier envelope
      phase stabilized laser source which delivers sub 4 fs pulses to a vibration
      isolated attosecond vacuum beamline. The beamline is used for the generation of
      isolated attosecond pulses in the extreme ultraviolet (XUV) at kilohertz
      repetition rates through laser-driven high harmonic generation in gas targets.
      The beamline incorporates: interferometers for producing pulse sequences for pump
      probe studies; the facility to spectrally and spatially filter the harmonic
      radiation; an in-line spatially resolving XUV spectrometer; and a photoelectron
      spectroscopy chamber in which attosecond streaking is used to characterize the
      attosecond pulses. We discuss the technology and techniques behind the
      development of our complete system and summarize its performance. This versatile
      apparatus has enabled a number of new experimental investigations which we
      briefly describe.

PMID- 22852665
TI  - A wavelength modulation system for highly sensitive absorption spectroscopy.
AB  - We developed a newly designed wavelength modulation (WM) system for highly
      sensitive absorption spectroscopy. In our system, the WM is realized by yawing an
      output mirror in a monochromator. In order to control an amplitude Deltalambda of
      the WM in a wide range, we employed a forced vibration of a permanent magnet
      driven by a magnetic field of a solenoid. Our system has an advantage of that the
      WM amplitude Deltalambda can be adjusted in extensively wide range from 0.08 nm
      to 11 nm only by tuning a driving frequency of the applying current to the
      solenoid, because we utilize a resonance phenomenon of the forced vibration for
      adjustment of the WM amplitude. By using our system, we measured WM absorption
      spectra of a Cu(2)O thin film and found clearly spectral structures for weak 2-4P
      excitonic resonances in the WM absorption spectra.

PMID- 22852666
TI  - A dark-line two-dimensional magneto-optical trap of 85Rb atoms with high optical
      depth.
AB  - We describe the apparatus of a dark-line two-dimensional (2D) magneto-optical
      trap (MOT) of (85)Rb cold atoms with high optical depth (OD). Different from the
      conventional configuration, two (of three) pairs of trapping laser beams in our
      2D MOT setup do not follow the symmetry axes of the quadrupole magnetic field:
      they are aligned with 45 degrees  angles to the longitudinal axis. Two orthogonal
      repumping laser beams have a dark-line volume in the longitudinal axis at their
      cross over. With a total trapping laser power of 40 mW and repumping laser power
      of 18 mW, we obtain an atomic OD up to 160 in an electromagnetically induced
      transparency (EIT) scheme, which corresponds to an atomic-density-length product
      NL = 2.05 * 10(15) m(-2). In a closed two-state system, the OD can become as
      large as more than 600. Our 2D MOT configuration allows full optical access of
      the atoms in its longitudinal direction without interfering with the trapping and
      repumping laser beams spatially. Moreover, the zero magnetic field along the
      longitudinal axis allows the cold atoms maintain a long ground-state coherence
      time without switching off the MOT magnetic field, which makes it possible to
      operate the MOT at a high repetition rate and a high duty cycle. Our 2D MOT is
      ideal for atomic-ensemble-based quantum optics applications, such as EIT,
      entangled photon pair generation, optical quantum memory, and quantum information
      processing.

PMID- 22852667
TI  - Development of a time-resolved attenuated total reflectance spectrometer in far
      ultraviolet region.
AB  - A far-ultraviolet transient absorption spectrometer based on time-resolved
      attenuated total reflectance (ATR) has been developed and tested for aqueous
      solutions of phenol and tryptophan in the region 170-185 nm. In this region, a
      stable tunable laser was not available, and therefore, white light from a laser
      driven Xe lamp source was used. The time resolution, which was determined by the
      time response of a continuous light detector, was 40 ns. A new ATR cell where a
      sample liquid is exchanged continuously by a flow system was designed to reduce
      efficiently the stray light from the excitation light. We have tested the
      performance of the instrument by using aqueous solutions of phenol and
      tryptophan, whose photochemistry is already well known. Phenol and tryptophan
      have very strong absorptions due to a pi-pi* transition near 180 nm. Even for
      dilute solutions (10(-3) mol dm(-3)), we could observe decreases in their
      concentrations due to photochemistry that occurred upon their irradiation with a
      fourth harmonic generation laser pulse produced by an Nd:YAG laser. The
      sensitivity of the spectrometer was about 10(-4) abs, which corresponded to a
      concentration variation of 10(-3) mol dm(-3) for phenol and tryptophan.

PMID- 22852668
TI  - Study of liquid jet instability by confocal microscopy.
AB  - The instability of a liquid microjet was used to measure the dynamic surface
      tension of liquids at the surface ages of <=1 ms using confocal microscopy. The
      reflected light from a laser beam at normal incidence to the jet surface is
      linear in the displacement of the surface near the confocal position, leading to
      a radial resolution of 4 nm and a dynamic range of 4 MUm in the surface position,
      thus permitting the measurement of amplitude of oscillation at the very early
      stage of jet instability. For larger oscillations outside the linear region of
      the confocal response, the swell and neck position of the jet can be located
      separately and the amplitude of oscillation determined with an accuracy of 0.2
      MUm. The growth rate of periodically perturbed water and ethanol/water mixture
      jets with a 100-MUm diameter nozzle and mean velocity of 5.7 m s(-1) has been
      measured. The dynamic surface tension was determined from the growth rate of the
      instability with a linear, axisymmetric, constant property model. Synchronisation
      of the confocal imaging system with the perturbation applied to the jet permitted
      a detailed study of the temporal evolution of the neck into a ligament and
      eventually into a satellite drop.

PMID- 22852669
TI  - An ultra low noise telecom wavelength free running single photon detector using
      negative feedback avalanche diode.
AB  - It is challenging to implement genuine free running single-photon detectors for
      the 1550 nm wavelength range with simultaneously high detection efficiency (DE),
      low dark noise, and good time resolution. We report a novel read out system for
      the signals from a negative feedback avalanche diode (NFAD) [M. A. Itzler, X.
      Jiang, B. Nyman, and K. Slomkowski, "Quantum sensing and nanophotonic devices
      VI," Proc. SPIE 7222, 72221K (2009); X. Jiang, M. A. Itzler, K. ODonnell, M.
      Entwistle, and K. Slomkowski, "Advanced photon counting techniques V," Proc. SPIE
      8033, 80330K (2011); M. A. Itzler, X. Jiang, B. M. Onat, and K. Slomkowski,
      "Quantum sensing and nanophotonic devices VII," Proc. SPIE 7608, 760829 (2010)],
      which allows useful operation of these devices at a temperature of 193 K and
      results in very low darkcounts (~100 counts per second (CPS)), good time jitter
      (~30 ps), and good DE (~10%). We characterized two NFADs with a time-correlation
      method using photons generated from weak coherent pulses and photon pairs
      produced by spontaneous parametric down conversion. The inferred detector
      efficiencies for both types of photon sources agree with each other. The best
      noise equivalent power of the device is estimated to be 8.1 * 10(-18) W Hz(-1/2),
      more than 10 times better than typical InP/InGaAs single photon avalanche diodes
      (SPADs) show in free running mode. The afterpulsing probability was found to be
      less than 0.1% per ns at the optimized operating point. In addition, we studied
      the performance of an entanglement-based quantum key distribution (QKD) using
      these detectors and develop a model for the quantum bit error rate that
      incorporates the afterpulsing coefficients. We verified experimentally that using
      these NFADs it is feasible to implement QKD over 400 km of telecom fiber. Our
      NFAD photon detector system is very simple, and is well suited for single-photon
      applications where ultra-low noise and free-running operation is required, and
      some afterpulsing can be tolerated.

PMID- 22852670
TI  - Measurement of xenon plasma properties in an ion thruster using laser Thomson
      scattering technique.
AB  - This paper reports on the development of a method for measuring xenon plasma
      properties using the laser Thomson scattering technique, for application to ion
      engine system design. The thresholds of photo-ionization of xenon plasma were
      investigated and the number density of metastable atoms, which are photo-ionized
      by a probe laser, was measured using laser absorption spectroscopy, for several
      conditions. The measured threshold energy of the probe laser using a plano-convex
      lens with a focal length of 200 mm was 150 mJ for a xenon mass flow rate of 20
      MUg/s and incident microwave power of 6 W; the probe laser energy was therefore
      set as 80 mJ. Electron number density was found to be (6.2 +/- 0.4) * 10(17) m(
      3) and electron temperature was found to be 2.2 +/- 0.4 eV at a xenon mass flow
      rate of 20 MUg/s and incident microwave power of 6 W. The threshold of the probe
      laser intensity against photo-ionization in a miniature xenon ion thruster is
      almost constant for various mass flow rates, since the ratio of population of the
      metastable atoms to the electron number density is little changed.

PMID- 22852671
TI  - Phase-shifting interferometer using a frequency-tunable diode laser calibrated by
      an optical frequency comb.
AB  - We present a phase-shifting interferometer based on a frequency-tunable diode
      laser calibrated by an optical frequency comb and the Carre algorithm. By use of
      the frequency control strategies of locking the diode laser to different comb
      modes and scanning the repetition rate, an arbitrary single optical frequency
      synthesizer is obtained. The relative laser frequency uncertainty is 5.7 * 10(
      12) for 1 s averaging time with tracing to an Rb clock and accurate phase steps
      are achieved by optical frequency tuning. The surface topography of a standard
      sphere is measured by this phase-shifting interferometer based on a flat
      reference. The phase measurement repeatability is lambda/200. With this
      technique, phase measurement uncertainties from the laser frequency and phase
      steps are negligible.

PMID- 22852672
TI  - Application of gauge R&R to the rigorous measurement of quantum yield in
      fluorescent organic solid state systems.
AB  - A rigorous measurement of the photoluminescence quantum yield (PLQY) of three
      luminescent solid state organic material systems is presented. Poly(9,9
      dioctylfluorene), perylene (2.97 M in poly(methyl methacrylate)), and perylene
      red (0.78 M in poly(methyl methacrylate)), were measured using a Ti:sapphire
      laser yielding 47 +/- 3%, 79 +/- 3%, and 51 +/- 2%, respectively. A GaN diode
      laser with differing variability was used to measure the PLQY for perylene and
      perylene red yielding 71 +/- 1% and 53 +/- 2%, respectively. Variations due to
      sample preparation (<0.5%), sample degradation (none), and measurement system
      repeatability (Ti:sapphire ~2%, GaN ~1%) have been determined for each material.
      Variance in laser intensity is found to be the largest source of error which upon
      propagation to the PLQY, agrees closely with the uncertainty found by means of
      the rigorous statistics. This suggests reduction of laser intensity variation
      could allow much greater precision in absolute determinations of PLQY. Some small
      systematic bias from calibration and self-absorption corrections cannot be ruled
      out. The current limit of precision for this measurement is +/-1% using the more
      stable GaN laser though this apparently depends on the material and sample
      fabrication.

PMID- 22852673
TI  - A threshold-based approach to calorimetry in helium droplets: measurement of
      binding energies of water clusters.
AB  - Helium droplet beam methods have emerged as a versatile technique that can be
      used to assemble a wide variety of atomic and molecular clusters. We have
      developed a method to measure the binding energies of clusters assembled in
      helium droplets by determining the minimum droplet sizes required to assemble and
      detect selected clusters in the spectrum of the doped droplet beam. The
      differences in the droplet sizes required between the various multimers are then
      used to estimate the incremental binding energies. We have applied this method to
      measure the binding energies of cyclic water clusters from the dimer to the
      tetramer. We obtain measured values of D(0) that are in agreement with
      theoretical estimates to within ~20%. Our results suggest that this threshold
      based approach should be generally applicable using either mass spectrometry or
      optical spectroscopy techniques for detection, provided that the clusters
      selected for study are at least as strongly bound as those of water, and that a
      peak in the overall spectrum of the beam corresponding only to the cluster chosen
      (at least in the vicinity of the threshold) can be located.

PMID- 22852674
TI  - In situ multipurpose time-resolved spectrometer for monitoring nanoparticle
      generation in a high-pressure fluid.
AB  - We developed a multipurpose time-resolved spectrometer for studying the dynamics
      of nanoparticles generated by pulsed-laser ablation (PLA) in a high-pressure
      fluid. The apparatus consists of a high-pressure optical cell and three
      spectrometers for in situ measurements. The optical cell was designed for
      experiments at temperatures up to 400 K and pressures up to 30 MPa with
      fluctuations within +/-0.1% h(-1). The three spectrometers were used for the
      following in situ measurements at high pressures: (i) transient absorption
      spectrum measurements from 350 to 850 nm to investigate the dynamics of
      nanoparticle generation from nanoseconds to milliseconds after laser irradiation,
      (ii) absorption spectrum measurements from 220 to 900 nm to observe the time
      evolution of nanoparticles from seconds to hours after laser ablation, and (iii)
      dynamic light scattering measurements to track nanoparticles with sizes from 10
      nm to 10 MUm in the time range from seconds to hours after laser ablation. By
      combining these three spectrometers, we demonstrate in situ measurements of gold
      nanoparticles generated by PLA in supercritical fluids. This is the first report
      of in situ time-resolved measurements of the dynamics of nanoparticles generated
      in a supercritical fluid.

PMID- 22852675
TI  - Temperature diagnostics of ECR plasma by measurement of electron bremsstrahlung.
AB  - The x-ray bremsstrahlung spectrum emitted by the electron population in a 14.5
      GHz ECR plasma source has been measured using a NaI(Tl) detector, and hence the
      electron temperature of the higher energy electron population in the plasma has
      been determined. The x-ray spectra for Ne and Ar gases have been systematically
      studied as a function of inlet gas pressure from 7 * 10(-7) mbar to 7 * 10(-5)
      mbar and for input microwave power ~1 W to ~300 W. At the highest input power and
      optimum pressure conditions, the end point bremsstrahlung energies are seen to
      reach ~700 keV. The estimated electron temperatures (T(e)) were found to be in
      the range 20 keV-80 keV. The T(e) is found to be peaking at a pressure of 1 * 10(
      5) mbar for both gases. The T(e) is seen to increase with increasing input power
      in the intermediate power region, i.e., between 100 and 200 W, but shows
      different behaviour for different gases in the low and high power regions. Both
      gases show very weak dependence of electron temperature on inlet gas pressure,
      but the trends in each gas are different.

PMID- 22852676
TI  - Versatile cold atom target apparatus.
AB  - We report on a compact and transportable apparatus that consists of a cold atomic
      target at the center of a high resolution recoil ion momentum spectrometer. Cold
      rubidium atoms serve as a target which can be operated in three different modes:
      in continuous mode, consisting of a cold atom beam generated by a two-dimensional
      magneto-optical trap, in normal mode in which the atoms from the beam are trapped
      in a three-dimensional magneto-optical trap (3D MOT), and in high density mode in
      which the 3D MOT is operated in dark spontaneous optical trap configuration. The
      targets are characterized using photoionization.

PMID- 22852677
TI  - Frequency multiplexed superconducting quantum interference device readout of
      large bolometer arrays for cosmic microwave background measurements.
AB  - A technological milestone for experiments employing transition edge sensor
      bolometers operating at sub-Kelvin temperature is the deployment of detector
      arrays with 100s-1000s of bolometers. One key technology for such arrays is
      readout multiplexing: the ability to read out many sensors simultaneously on the
      same set of wires. This paper describes a frequency-domain multiplexed readout
      system which has been developed for and deployed on the APEX-SZ and South Pole
      Telescope millimeter wavelength receivers. In this system, the detector array is
      divided into modules of seven detectors, and each bolometer within the module is
      biased with a unique ~MHz sinusoidal carrier such that the individual bolometer
      signals are well separated in frequency space. The currents from all bolometers
      in a module are summed together and pre-amplified with superconducting quantum
      interference devices operating at 4 K. Room temperature electronics demodulate
      the carriers to recover the bolometer signals, which are digitized separately and
      stored to disk. This readout system contributes little noise relative to the
      detectors themselves, is remarkably insensitive to unwanted microphonic
      excitations, and provides a technology pathway to multiplexing larger numbers of
      sensors.

PMID- 22852679
TI  - Measurement of fast-changing low velocities by photonic Doppler velocimetry.
AB  - Despite the increasing popularity of photonic Doppler velocimetry (PDV) in shock
      wave experiments, its capability of capturing low particle velocities while
      changing rapidly is still questionable. The paper discusses the performance of
      short time Fourier transform (STFT) and continuous wavelet transform (CWT) in
      processing fringe signals of fast-changing low velocities measured by PDV. Two
      typical experiments are carried out to evaluate the performance. In the laser
      shock peening test, the CWT gives a better interpretation to the free surface
      velocity history, where the elastic precursor, main plastic wave, and elastic
      release wave can be clearly identified. The velocities of stress waves, Hugoniot
      elastic limit, and the amplitude of shock pressure induced by laser can be
      obtained from the measurement. In the Kolsky-bar based tests, both methods show
      validity of processing the longitudinal velocity signal of incident bar, whereas
      CWT improperly interprets the radial velocity of the shocked sample at the
      beginning period, indicating the sensitiveness of the CWT to the background
      noise. STFT is relatively robust in extracting waveforms of low signal-to-noise
      ratio. Data processing method greatly affects the temporal resolution and
      velocity resolution of a given fringe signal, usually CWT demonstrates a better
      local temporal resolution and velocity resolution, due to its adaptability to the
      local frequency, also due to the finer time-frequency product according to the
      uncertainty principle.

PMID- 22852678
TI  - A multi-crystal wavelength dispersive x-ray spectrometer.
AB  - A multi-crystal wavelength dispersive hard x-ray spectrometer with high-energy
      resolution and large solid angle collection is described. The instrument is
      specifically designed for time-resolved applications of x-ray emission
      spectroscopy (XES) and x-ray Raman scattering (XRS) at X-ray Free Electron Lasers
      (XFEL) and synchrotron radiation facilities. It also simplifies resonant
      inelastic x-ray scattering (RIXS) studies of the whole 2d RIXS plane. The
      spectrometer is based on the Von Hamos geometry. This dispersive setup enables an
      XES or XRS spectrum to be measured in a single-shot mode, overcoming the scanning
      needs of the Rowland circle spectrometers. In conjunction with the XFEL temporal
      profile and high-flux, it is a powerful tool for studying the dynamics of time
      dependent systems. Photo-induced processes and fast catalytic reaction kinetics,
      ranging from femtoseconds to milliseconds, will be resolvable in a wide array of
      systems circumventing radiation damage.

PMID- 22852680
TI  - Development of double-decker pulse radiolysis.
AB  - Double-decker pulse radiolysis (DDPR), which utilizes double-decker electron
      beams, was investigated to develop a new pulse radiolysis with a high time
      resolution. The double-decker electron beams were generated by injecting two UV
      pulses into a photocathode radio-frequency gun. In the pulse radiolysis, one
      electron beam was used as a pump beam, and the other was converted to a probe
      pulse. Finally, as its first application, the DDPR was successfully used for
      observing solvated electrons in water, with a 10%-90% rise time of 8.6 ps.

PMID- 22852681
TI  - A multi-detector, digitizer based neutron depth profiling device for
      characterizing thin film materials.
AB  - Neutron depth profiling (NDP) is a mature, nondestructive technique used to
      characterize the concentration of certain light isotopes in a material as a
      function of depth by measuring the residual energy of charged particles in
      neutron induced reactions. Historically, NDP has been performed using a single
      detector, resulting in low intrinsic detection efficiency, and limiting the
      technique largely to high flux research reactors. In this work, we describe a new
      NDP instrument design with higher detection efficiency by way of spectrum summing
      across multiple detectors. Such a design is capable of acquiring a statistically
      significant charged particle spectrum at facilities limited in neutron flux and
      operation time.

PMID- 22852682
TI  - Design and capabilities of an experimental setup based on magnetron sputtering
      for formation and deposition of size-selected metal clusters on ultra-clean
      surfaces.
AB  - The design and performance of an experimental setup utilizing a magnetron
      sputtering source for production of beams of ionized size-selected clusters for
      deposition in ultra-high vacuum is described. For the case of copper cluster
      formation the influence of different source parameters is studied and analyzed.
      Size-selected clusters are deposited on substrates and the efficiency of an
      electrostatic quadrupole mass selector is tested. Height analysis using atomic
      force microscopy (AFM) demonstrates relative standard size deviations of 7%-10%
      for the particles of various sizes between 6 nm and 19 nm. Combined analysis by
      AFM and transmission electron microscopy reveals that the clusters preserve
      almost spherical shape after the deposition on amorphous carbon substrates.
      Supported nanoparticles of a few nanometres in diameter have crystalline
      structure with a face-centered cubic (fcc) lattice.

PMID- 22852683
TI  - Optimization of a charge-state analyzer for electron cyclotron resonance ion
      source beams.
AB  - A detailed experimental and simulation study of the extraction of a 24 keV He(+)
      beam from an ECR ion source and the subsequent beam transport through an
      analyzing magnet is presented. We find that such a slow ion beam is very
      sensitive to space-charge forces, but also that the neutralization of the beam's
      space charge by secondary electrons is virtually complete for beam currents up to
      at least 0.5 mA. The beam emittance directly behind the extraction system is 65
      pi mm mrad and is determined by the fact that the ion beam is extracted in the
      strong magnetic fringe field of the ion source. The relatively large emittance of
      the beam and its non-paraxiality lead, in combination with a relatively small
      magnet gap, to significant beam losses and a five-fold increase of the effective
      beam emittance during its transport through the analyzing magnet. The calculated
      beam profile and phase-space distributions in the image plane of the analyzing
      magnet agree well with measurements. The kinematic and magnet aberrations have
      been studied using the calculated second-order transfer map of the analyzing
      magnet, with which we can reproduce the phase-space distributions of the ion beam
      behind the analyzing magnet. Using the transfer map and trajectory calculations
      we have worked out an aberration compensation scheme based on the addition of
      compensating hexapole components to the main dipole field by modifying the shape
      of the poles. The simulations predict that by compensating the kinematic and
      geometric aberrations in this way and enlarging the pole gap the overall beam
      transport efficiency can be increased from 16% to 45%.

PMID- 22852684
TI  - A high power ion thruster for deep space missions.
AB  - The Nuclear Electric Xenon Ion System ion thruster was developed for potential
      outer planet robotic missions using nuclear electric propulsion (NEP). This
      engine was designed to operate at power levels ranging from 13 to 28 kW at
      specific impulses of 6000-8500 s and for burn times of up to 10 years. State-of
      the-art performance and life assessment tools were used to design the thruster,
      which featured 57-cm-diameter carbon-carbon composite grids operating at voltages
      of 3.5-6.5 kV. Preliminary validation of the thruster performance was
      accomplished with a laboratory model thruster, while in parallel, a flight-like
      development model (DM) thruster was completed and two DM thrusters fabricated.
      The first thruster completed full performance testing and a 2000-h wear test. The
      second successfully completed vibration tests at the full protoflight levels
      defined for this NEP program and then passed performance validation testing. The
      thruster design, performance, and the experimental validation of the design tools
      are discussed in this paper.

PMID- 22852685
TI  - Optics of ion beams for the neutral beam injection system on HL-2A Tokamak.
AB  - The ion beam optics for the neutral beam injection system on HL-2A Tokomak is
      studied by two- dimensional numerical simulation program firstly, where the
      emitting surface is taken at 100 Debye lengths from the plasma electrode. The
      mathematical formulation, computation techniques are described. Typical ion
      orbits, equipotential contours, and emittance diagram are shown. For a fixed
      geometry electrode, the effect of plasma density, plasma potential and plasma
      electron temperature on ion beam optics is examined, and the calculation
      reliability is confirmed by experimental results. In order to improve ion beam
      optics, the application of a small pre-acceleration voltage (~100 V) between the
      plasma electrode and the arc discharge anode is reasonable, and a lower plasma
      electron temperature is desired. The results allow optimization of the ion beam
      optics in the neutral beam injection system on HL-2A Tokomak and provide
      guidelines for designing future neutral beam injection system on HL-2M Tokomak.

PMID- 22852686
TI  - Ultraviolet stimulated electron source for use with low energy plasma instrument
      calibration.
AB  - We have developed and demonstrated a versatile, compact electron source that can
      produce a mono-energetic electron beam up to 50 mm in diameter from 0.1 to 30 keV
      with an energy spread of <10 eV. By illuminating a metal cathode plate with a
      single near ultraviolet light emitting diode, a spatially uniform electron beam
      with 15% variation over 1 cm(2) can be generated. A uniform electric field in
      front of the cathode surface accelerates the electrons into a beam with an
      angular divergence of <1 degrees  at 1 keV. The beam intensity can be controlled
      from 10 to 10(9) electrons cm(-2) s(-1).

PMID- 22852687
TI  - Shot-to-shot reproducibility of a self-magnetically insulated ion diode.
AB  - In this paper we present the analysis of shot to shot reproducibility of the ion
      beam which is formed by a self-magnetically insulated ion diode with an explosive
      emission graphite cathode. The experiments were carried out with the TEMP-4M
      accelerator operating in double-pulse mode: the first pulse is of negative
      polarity (300-500 ns, 100-150 kV), and this is followed by a second pulse of
      positive polarity (150 ns, 250-300 kV). The ion current density was 10-70 A/cm(2)
      depending on the diode geometry. The beam was composed from carbon ions (80%-85%)
      and protons. It was found that shot to shot variation in the ion current density
      was about 35%-40%, whilst the diode voltage and current were comparatively stable
      with the variation limited to no more than 10%. It was shown that focusing of the
      ion beam can improve the stability of the ion current generation and reduces the
      variation to 18%-20%. In order to find out the reason for the shot-to-shot
      variation in ion current density we examined the statistical correlation between
      the current density of the accelerated beam and other measured characteristics of
      the diode, such as the accelerating voltage, total current, and first pulse
      duration. The correlation between the ion current density measured simultaneously
      at different positions within the cross-section of the beam was also
      investigated. It was shown that the shot-to-shot variation in ion current density
      is mainly attributed to the variation in the density of electrons diffusing from
      the drift region into the A-K gap.

PMID- 22852688
TI  - A novel compact repetitive frequency voltage booster based on magnetic switches
      and Fitch generator.
AB  - In this paper, a novel repetitive frequency voltage booster (named repetitive
      Fitch booster by the authors) based on magnetic switches and Fitch generators is
      proposed. The principle of operation is to charge capacitors in parallel when
      magnetic switches (MSs) are unsaturated and reverse voltage polarity of every
      other capacitor when MSs saturate. With the principle, circuit topology of a 4
      stage repetitive Fitch booster (RFB) is presented. Simulation as well as
      experiment shows its feasibility in boosting voltage and compressing rise-time.
      In simulation, the input voltage of 100 V is boosted to 372 V, while test stand
      yields output voltage with frequency of 1 kHz, amplitude of 19 kV with each
      capacitor charged to about 5.6 kV, and rise-time compression from 7.3 MUs to 700
      ns. Meanwhile, calculations show that the 4-stage RFB effectively reduces core
      volume by about half, from 1093.5 cm(3) to 585.2 cm(3). Furthermore, design rules
      are proposed so that topologies of RFBs with stages other than four can be
      conveniently derived. As an example, an 8-stage RFB is proposed and verified with
      circuit simulation, which shows an output voltage of 759 V with the input voltage
      of 100 V.

PMID- 22852689
TI  - Energetic ion loss detector on the Alcator C-Mod tokamak.
AB  - A scintillator-based energetic ion loss detector has been successfully
      commissioned on the Alcator C-Mod tokamak. This probe is located just below the
      outer midplane, where it captures ions of energies up to 2 MeV resulting from ion
      cyclotron resonance heating. After passing through a collimating aperture, ions
      impact different regions of the scintillator according to their gyroradius
      (energy) and pitch angle. The probe geometry and installation location are
      determined based on modeling of expected lost ions. The resulting probe is
      compact and resembles a standard plasma facing tile. Four separate fiber optic
      cables view different regions of the scintillator to provide phase space
      resolution. Evolving loss levels are measured during ion cyclotron resonance
      heating, including variation dependent upon individual antennae.

PMID- 22852690
TI  - Calibration and analysis of spatially resolved x-ray absorption spectra from a
      nonuniform plasma.
AB  - We report here the calibration and analysis techniques used to obtain spatially
      resolved density and temperature measurements of a pair of imploding aluminum
      wires from x-ray absorption spectra. A step wedge is used to measure backlighter
      fluence at the film, allowing transmission through the sample to be measured with
      an accuracy of +/-14% or better. A genetic algorithm is used to search the
      allowed plasma parameter space and fit synthetic spectra with 20 MUm spatial
      resolution to the measured spectra, taking into account that the object plasma
      nonuniformity must be physically reasonable. The inferred plasma conditions must
      be allowed to vary along the absorption path in order to obtain a fit to the
      spectral data. The temperature is estimated to be accurate to within +/-25% and
      the density to within a factor of two. This information is used to construct two
      dimensional maps of the density and temperature of the object plasma.

PMID- 22852691
TI  - Stereolithography based method of creating custom gas density profile targets for
      high intensity laser-plasma experiments.
AB  - Laser based stereolithography methods are shown to be useful for production of
      gas targets for high intensity laser-plasma interaction experiments. A
      cylindrically symmetric nozzle with an opening of approximately 100 MUm and a
      periodic attachment of variable periodicity are outlined in detail with
      associated density profile characterization. Both components are durable within
      the limits of relevant experiments.

PMID- 22852692
TI  - Plasma-accelerated flyer-plates for equation of state studies.
AB  - We report on a new technique to accelerate flyer-plates to high velocities (~5
      km/s). In this work, a strong shock is created through direct laser ablation of a
      thin polyimide foil. Subsequent shock breakout of that foil results in the
      generation of a plasma characterized by a smoothly increasing density gradient
      and a strong forward momentum. Stagnation of this plasma onto an aluminum foil
      and the resultant momentum transfer accelerates a thin aluminum flyer-plate. The
      aluminum flyer-plate is then accelerated to a peak velocity of ~5 km/s before
      impact with a transparent lithium fluoride (LiF) window. Simulations of the
      stagnating plasma ramp compression and wave reverberations within the flyer-plate
      suggest that the temperature at the flyer-plate impact surface is elevated by
      less than 50  degrees C. Optical velocimetry is used to measure the flyer-plate
      velocity and impact conditions enabling the shocked refractive index of LiF to be
      determined. The results presented here are in agreement with conventional flyer
      plate measurements validating the use of plasma-accelerated flyer-plates for
      equation of state and impact studies.

PMID- 22852693
TI  - A high-field adiabatic fast passage ultracold neutron spin flipper for the UCNA
      experiment.
AB  - The UCNA collaboration is making a precision measurement of the beta asymmetry
      (A) in free neutron decay using polarized ultracold neutrons (UCN). A critical
      component of this experiment is an adiabatic fast passage neutron spin flipper
      capable of efficient operation in ambient magnetic fields on the order of 1 T.
      The requirement that it operate in a high field necessitated the construction of
      a free neutron spin flipper based, for the first time, on a birdcage resonator.
      The design, construction, and initial testing of this spin flipper prior to its
      use in the first measurement of A with UCN during the 2007 run cycle of the Los
      Alamos Neutron Science Center's 800 MeV proton accelerator is detailed. These
      studies determined the flipping efficiency of the device, averaged over the UCN
      spectrum present at the location of the spin flipper, to be epsilon=0.9985(4).

PMID- 22852694
TI  - Improved analysis techniques for cylindrical and spherical double probes.
AB  - A versatile double Langmuir probe technique has been developed by incorporating
      analytical fits to Laframboise's numerical results for ion current collection by
      biased electrodes of various sizes relative to the local electron Debye length.
      Application of these fits to the double probe circuit has produced a set of
      coupled equations that express the potential of each electrode relative to the
      plasma potential as well as the resulting probe current as a function of applied
      probe voltage. These equations can be readily solved via standard numerical
      techniques in order to determine electron temperature and plasma density from
      probe current and voltage measurements. Because this method self-consistently
      accounts for the effects of sheath expansion, it can be readily applied to
      plasmas with a wide range of densities and low ion temperature (T(i)/T(e) ? 1)
      without requiring probe dimensions to be asymptotically large or small with
      respect to the electron Debye length. The presented approach has been
      successfully applied to experimental measurements obtained in the plume of a low
      power Hall thruster, which produced a quasineutral, flowing xenon plasma during
      operation at 200 W on xenon. The measured plasma densities and electron
      temperatures were in the range of 1 * 10(12)-1 * 10(17) m(-3) and 0.5-5.0 eV,
      respectively. The estimated measurement uncertainty is +6%/-34% in density and +/
      30% in electron temperature.

PMID- 22852695
TI  - Elemental and magnetic sensitive imaging using x-ray excited luminescence
      microscopy.
AB  - We demonstrate the potential of x-ray excited luminescence microscopy for full
      field elemental and magnetic sensitive imaging using a commercially available
      optical microscope, mounted on preexisting synchrotron radiation (SR) beamline
      end stations. The principal components of the instrument will be described. Bench
      top measurements indicate that a resolution of 1 MUm or better is possible; this
      value was degraded in practice due to vibrations and/or drift in the end station
      and associated manipulator. X-ray energy dependent measurements performed on
      model solar cell materials and lithographically patterned magnetic thin film
      structures reveal clear elemental and magnetic signatures. The merits of the
      apparatus will be discussed in terms of conventional SR imaging techniques.

PMID- 22852696
TI  - Scanning superconducting quantum interference device on a tip for magnetic
      imaging of nanoscale phenomena.
AB  - We describe a new type of scanning probe microscope based on a superconducting
      quantum interference device (SQUID) that resides on the apex of a sharp tip. The
      SQUID-on-tip is glued to a quartz tuning fork which allows scanning at a tip
      sample separation of a few nm. The magnetic flux sensitivity of the SQUID is 1.8
      MUPhi(0)/?Hz and the spatial resolution is about 200 nm, which can be further
      improved. This combination of high sensitivity, spatial resolution, bandwidth,
      and the very close proximity to the sample provides a powerful tool for study of
      dynamic magnetic phenomena on the nanoscale. The potential of the SQUID-on-tip
      microscope is demonstrated by imaging of the vortex lattice and of the local ac
      magnetic response in superconductors.

PMID- 22852697
TI  - An instrument for 3D x-ray nano-imaging.
AB  - We present an instrument dedicated to 3D scanning x-ray microscopy, allowing a
      sample to be precisely scanned through a beam while the angle of x-ray incidence
      can be changed. The position of the sample is controlled with respect to the beam
      defining optics by laser interferometry. The instrument achieves a position
      stability better than 10 nm standard deviation. The instrument performance is
      assessed using scanning x-ray diffraction microscopy and we demonstrate a
      resolution of 18 nm in 2D imaging of a lithographic test pattern while the beam
      was defined by a pinhole of 3 MUm in diameter. In 3D on a test object of copper
      interconnects of a microprocessor, a resolution of 53 nm is achieved.

PMID- 22852698
TI  - Elastic constants of langasite and alpha quartz at high temperatures measured by
      antenna transmission acoustic resonance.
AB  - A method for measuring elastic constants of piezoelectric materials at high
      temperature up to 1224 K is proposed. It determines all independent elastic
      constants by measuring resonance frequencies of a rectangular parallelepiped
      piezoelectric specimen contactlessly using its own piezoelectricity with an
      antenna. Without using conventional contacting piezoelectric transducers,
      vibrational sources are excited directly in the specimen by the oscillating
      electric field. Capability of the method is demonstrated by measuring the elastic
      constants of langasite at high temperature up to 1224 K, and temperature
      coefficients of the elastic constants are determined. In addition, elastic
      constants of alpha quartz are measured at high temperature up to just below the
      alpha-beta phase transition temperature. Considering the local deformation with
      temperature increment, an interpretation based on the strain energy reduction is
      proposed for the unusual temperature dependence of C(66). Furthermore, the
      internal-friction tensor is measured, and the relationship between the observed
      anisotropy in internal friction and the structural evolution with temperature
      increment is discussed.

PMID- 22852699
TI  - Joint strength measurements of individual fiber-fiber bonds: an atomic force
      microscopy based method.
AB  - We are introducing a method to measure tensile strength of individual fiber-fiber
      bonds within a breaking force range of 0.01 mN-1 mN as well as the energy
      consumed during breaking. Until now, such a method was not available. Using a
      conventional atomic force microscope and a specifically designed sample holder,
      the desired force and the breaking behavior can be analyzed by two different
      approaches. First, dynamic loading can be applied, where force-versus-distance
      curves are employed to determine the proportions of elastic energy and energy
      dissipated in the bond. Second, static loading is utilized to study viscoelastic
      behavior and calculate viscoelastic energy contributions. To demonstrate the
      capability of the proposed method, we are presenting results for breaking
      strength of kraft pulp fiber-fiber bonds in tensile opening mode. The procedure
      is by no means restricted to cellulose fibers, it has the potential to quantify
      joint strength of micrometer-sized fibers in general.

PMID- 22852700
TI  - Gas gun shock experiments with single-pulse x-ray phase contrast imaging and
      diffraction at the Advanced Photon Source.
AB  - The highly transient nature of shock loading and pronounced microstructure
      effects on dynamic materials response call for in situ, temporally and spatially
      resolved, x-ray-based diagnostics. Third-generation synchrotron x-ray sources are
      advantageous for x-ray phase contrast imaging (PCI) and diffraction under dynamic
      loading, due to their high photon fluxes, high coherency, and high pulse
      repetition rates. The feasibility of bulk-scale gas gun shock experiments with
      dynamic x-ray PCI and diffraction measurements was investigated at the beamline
      32ID-B of the Advanced Photon Source. The x-ray beam characteristics,
      experimental setup, x-ray diagnostics, and static and dynamic test results are
      described. We demonstrate ultrafast, multiframe, single-pulse PCI measurements
      with unprecedented temporal (<100 ps) and spatial (~2 MUm) resolutions for bulk
      scale shock experiments, as well as single-pulse dynamic Laue diffraction. The
      results not only substantiate the potential of synchrotron-based experiments for
      addressing a variety of shock physics problems, but also allow us to identify the
      technical challenges related to image detection, x-ray source, and dynamic
      loading.

PMID- 22852701
TI  - A combined surface stress and magneto-optical Kerr effect measurement setup for
      temperatures down to 30 K and in fields of up to 0.7 T.
AB  - An optical 2-beam surface stress measurement and magneto-optical Kerr-effect has
      been combined with a liquid helium cooled cryostat. Sample temperatures down to
      30 K and magnetic fields up to 0.7 T are achieved under UHV conditions. Low
      temperatures are exploited to obtain the first experimental data on the surface
      stress change induced by the adsorption of the noble gas Xe on Pt(111). High
      magnetic fields and low temperatures are used to characterize the magnetic
      properties of Co monolayers in longitudinal and polar Kerr geometries. The
      effective magnetic anisotropy is extracted from hard axis magnetization loops.

PMID- 22852702
TI  - Facile characterization of ripple domains on exfoliated graphene.
AB  - Ripples in graphene monolayers deposited on SiO(2)/Si wafer substrates were
      recently shown to give rise to friction anisotropy. High friction appears when
      the AFM tip slides in a direction perpendicular to the ripple crests and low
      friction when parallel. The direction of the ripple crest is, however, hard to
      determine as it is not visible in topographic images and requires elaborate
      measurements of friction as a function of angle. Here we report a simple method
      to characterize ripple crests by measuring the cantilever torsion signal while
      scanning in the non-conventional longitudinal direction (i.e., along the
      cantilever axis, as opposed to the usual friction measurement). The longitudinal
      torsion signal provides a much clearer ripple domain contrast than the
      conventional friction signal, while both signals show respective rotation angle
      dependences that can be explained using the torsion component of the normal
      reaction force exerted by the graphene ripples. We can also determine the ripple
      direction by comparing the contrast in torsion images obtained in longitudinal
      and lateral scans without sample rotation or complicated normalization.

PMID- 22852703
TI  - Low frequency pressure modulation of indium antimonide.
AB  - A lumped parameter resonator capable of generating megapascal pressures at low
      frequency (kilohertz) is described. Accelerometers are used to determine the
      applied pressure, and are calibrated with a piezoelectric sample. A laser
      diagnostic was also developed to measure the pressure in semiconductor samples
      through the band gap pressure dependence. In addition, the laser diagnostic has
      been used to measure the attenuation coefficient alpha of commercially available
      indium antimonide (InSb) wafers. The resonator and laser diagnostic have been
      used with InSb samples to verify the pressure response.

PMID- 22852704
TI  - Monitoring microbial population dynamics at low densities.
AB  - We propose a new and simple method for the measurement of microbial
      concentrations in highly diluted cultures. This method is based on an analysis of
      the intensity fluctuations of light scattered by microbial cells under laser
      illumination. Two possible measurement strategies are identified and compared
      using simulations and measurements of the concentration of gold nanoparticles.
      Based on this comparison, we show that the concentration of Escherichia coli and
      Saccharomyces cerevisiae cultures can be easily measured in situ across a
      concentration range that spans five orders of magnitude. The lowest measurable
      concentration is three orders of magnitude (1000*) smaller than in current
      optical density measurements. We show further that this method can also be used
      to measure the concentration of fluorescent microbial cells. In practice, this
      new method is well suited to monitor the dynamics of population growth at early
      colonization of a liquid culture medium. The dynamic data thus obtained are
      particularly relevant for microbial ecology studies.

PMID- 22852705
TI  - Novel in situ normal streaming potential device for characterizing electrostatic
      properties of confluent cells.
AB  - The characteristics of transport across confluent cell monolayers may often be
      attributed to its electrostatic properties. While tangential streaming potential
      is often used to quantify these electrostatic properties, this method is not
      effective for transport normal to the apical cell surface where the charge
      properties along the basolateral sides may be important (i.e., confluent cells
      with leaky tight junctions). In addition, even when cells have a uniform charge
      distribution, the shear stress generated by the conventional tangential flow
      device may dislodge cells from their confluent state. Here we introduce a novel
      streaming potential measurement device to characterize the normal electrostatic
      properties of confluent cells. The streaming potential device encompasses a 24 mm
      cell-seeded Transwell((r)) with two AgCl electrodes on either side of the cell
      seeded Transwell. Phosphate buffered saline is pressurized transversal to the
      Transwell and the resultant pressure gradient induces a potential difference.
      Confluent monolayers of HEK and EA926 cells are used as examples. The
      corresponding zeta potential of the cell-membrane configuration is calculated
      using the Helmholtz-Smoluchowski equation and the zeta potential of the confluent
      cell layer is deconvolved from the overall measurements. For these test models,
      the zeta potential is consistent with that determined using a commercial
      dispersed-cell device. This novel streaming potential device provides a simple,
      easy, and cost-effective methodology to determine the normal zeta potential of
      confluent cells cultured on Transwell systems while keeping the cells intact.
      Furthermore, its versatility allows periodic measurements of properties of the
      same cell culture during transient studies.

PMID- 22852706
TI  - Methodology of evaluating the influence of the resistance of contact regions in
      the measurements of sheet resistance on stripes of ultrathin high-resistance
      materials.
AB  - The paper reviews the problems of measurement of sheet resistance of ultrathin
      high-resistance layers of organic semiconductors and the essential underlying
      problems. Particular attention is paid to potential influence of the resistance
      of contact regions on the results of direct measurement of sheet resistance of
      stripe-shaped layers. In this connection, we present a methodology of double
      length stripe resistance measurement (DLSRM), used above all to minimise the
      influence of contact regions on the measurement results. We deduce theoretical as
      well as practical possibilities of DLSRM in the diagnostics and quantitative
      characterisation of unsuitable or even faulty contacts on high-resistance layers.
      The application efficiency of the DLSRM method is documented by the results of
      sheet resistance measurement on zinc phthalocyanine with cathode sputtered planar
      contacts of noble metals (gold, platinum, or palladium). As expected, gold is the
      best contact material, but even in its application one cannot neglect the
      influence of contact regions. The presented method is universal and generally
      applicable to all materials where sheet resistance is the relevant parameter, and
      its assessment is based on measurements of the layer resistance in stripe
      arrangement.

PMID- 22852707
TI  - Effect of shock front geometry on shock depolarization of Pb(Zr(0.52)Ti(0.48))O3
      ferroelectric ceramics.
AB  - By use of experimentation, we detected a shock wave geometry effect on the
      depolarization of poled Pb(Zr(0.52)Ti(0.48))O(3) (PZT 52/48) ferroelectrics. It
      follows from the experimental results that shock front geometry is one of key
      parameters in the shock depolarization of PZT 52/48 ferroelectrics. This shock
      depolarization effect forms a fundamental limit to miniaturization of explosive
      driven shock-wave ferroelectric generators (FEGs). Based on obtained experimental
      results, we developed miniature generators that reliably produce pulsed voltages
      exceeding 140 kV.

PMID- 22852708
TI  - 10 ps resolution, 160 ns full scale range and less than 1.5% differential non
      linearity time-to-digital converter module for high performance timing
      measurements.
AB  - We present a compact high performance time-to-digital converter (TDC) module that
      provides 10 ps timing resolution, 160 ns dynamic range and a differential non
      linearity better than 1.5% LSB(rms). The TDC can be operated either as a general
      purpose time-interval measurement device, when receiving external START and STOP
      pulses, or in photon-timing mode, when employing the on-chip SPAD (single photon
      avalanche diode) detector for detecting photons and time-tagging them. The
      instrument precision is 15 ps(rms) (i.e., 36 ps(FWHM)) and in photon timing mode
      it is still better than 70 ps(FWHM). The USB link to the remote PC allows the
      easy setting of measurement parameters, the fast download of acquired data, and
      their visualization and storing via an user-friendly software interface. The
      module proves to be the best candidate for a wide variety of applications such
      as: fluorescence lifetime imaging, time-of-flight ranging measurements, time
      resolved positron emission tomography, single-molecule spectroscopy, fluorescence
      correlation spectroscopy, diffuse optical tomography, optical time-domain
      reflectometry, quantum optics, etc.

PMID- 22852709
TI  - New equipment for microwave electric field visualization.
AB  - We present the operation and design of newly developed, fully automatic equipment
      for the visualization of microwave electric fields. This equipment enables the
      observation of microwave field patterns around different objects including
      metamaterial prototypes and to study the field patterns of various microwave
      antennas and other objects that have been developed and that interact with a
      surrounding microwave electromagnetic field. Moreover, the developed prototypes
      whose interaction with an incident electromagnetic wave is crucial for practical
      applications can be investigated using size scaling, and hence our equipment can
      be used for the testing of antennas and other devices that interact with
      electromagnetic radiation, not only at microwave frequencies, but also at radio
      frequencies. The performance of our innovative equipment was demonstrated through
      the investigation of the metamaterial cloak. The frequency behavior of the
      metamaterial cloak revealed frequency bands with maximum cloaking efficiencies.

PMID- 22852710
TI  - Repetitive sub-gigawatt rf source based on gyromagnetic nonlinear transmission
      line.
AB  - We demonstrate a high power repetitive rf source using gyromagnetic nonlinear
      transmission line to produce rf oscillations. Saturated NiZn ferrites act as
      active nonlinear medium first sharpening the pumping high voltage nanosecond
      pulse and then radiating at central frequency of about 1 GHz: shock rise time
      excites gyromagnetic precession in ferrites forming damping rf oscillations. The
      optimal length of nonlinear transmission line was found to be of about 1 m. SINUS
      200 high voltage driver with Tesla transformer incorporated into pulse forming
      line has been designed and fabricated to produce bursts of 1000 pulses with 200
      Hz repetition rate. A band-pass filter and mode-converter have been designed to
      extract rf pulse from low-frequency component and to form TE(11) mode of circular
      waveguide with linear polarization. A wide-band horn antenna has been fabricated
      to form Gaussian distribution of radiation pattern. The peak value of electric
      field strength of a radiated pulse at the distance of 3.5 m away from antenna is
      measured to be 160 kV/m. The corresponding rf peak power of 260 MW was achieved.

PMID- 22852711
TI  - The K(a)-band 10-kW continuous wave gyrotron with wide-band fast frequency sweep.
AB  - The dual-frequency gyrotron with fast 2% frequency sweep at about 28 GHz is
      designed to power an electron cyclotron resonance ion source (ECRIS). Operation
      with an output power of up to 10 kW in CW mode and efficiency of 20% was
      demonstrated at both frequencies. Frequency manipulation has a characteristic
      time of about 1 ms and is based on magnetic field variation with an additional
      low-power coil. Fast frequency sweep will supposedly increase the ion current and
      the average ion charge of ECRIS. The possibility of 100% power modulation is
      demonstrated using the same control method.

PMID- 22852712
TI  - Development of integrated high temperature sensor for simultaneous measurement of
      wall heat flux and temperature.
AB  - In this paper, an integrated water-cooled sensor has been developed to
      simultaneously measure the heat flux and temperature at the wall of a scramjet
      combustor. The upgrade sensor was designed based on the principle of Gardon heat
      flux gauge with many improvements. The sensor was well calibrated by both
      conductive heating sources and blackbody cavity device. The effects of structural
      material and dimensions on the sensor's responses were examined. Both the
      experimental measurements and numerical simulation were conducted and showed that
      the new sensor has the maximum measure ability of heat flux of 400 W/cm(2) and
      stagnation temperatures up to 1920 K along with satisfactory response time.

PMID- 22852713
TI  - 2-omega and 3-omega temperature measurement of a heated microcantilever.
AB  - This article describes temperature measurement of a heated atomic force
      microscope cantilever using the 2omega and 3omega harmonics of the cantilever
      temperature signal. When the cantilever is periodically heated, large temperature
      oscillations lead to large changes in the cantilever electrical resistance and
      also lead to nonconstant temperature coefficient of resistance. We model the
      cantilever heating to account for these sources of nonlinearity, and compare
      models with experiment. When the heating voltage amplitude is 17.9 V over the
      driving frequency range 10 Hz-34 kHz, the cantilever temperature oscillation is
      between 5  degrees C and 200  degrees C. Over this range, the corrected 2omega
      method predicts cantilever temperature to within 16% and the corrected 3omega
      method predicts the cantilever temperature within 3%. We show a general method
      for predicting the periodic cantilever temperature, sources of errors, and
      corrections for these errors.

PMID- 22852715
TI  - Fully automated measurement setup for non-destructive characterization of
      thermoelectric materials near room temperature.
AB  - A measurement setup is presented that allows for a complete and non-destructive
      material characterization of electrochemically deposited thermoelectric material.
      All electrical (Seebeck coefficient alpha, electrical conductivity sigma),
      thermal (thermal conductivity lambda), and thermoelectric (figure of merit ZT)
      material parameters are determined within a single measurement run. The setup is
      capable of characterizing individual electrochemically deposited Bi(2+x)Te(3-x)
      pillars of various size and thickness down to a few 10 MUm, embedded in a polymer
      matrix with a maximum measurement area of 1 * 1 cm(2). The temperature range is
      limited to an application specific window near room temperature of 10  degrees C
      to 70  degrees C. A maximum thermal flux of 1 W/cm(2) can be applied to the
      device under test (DUT) by the Peltier element driven heat source and sink. The
      setup has a highly symmetric design and DUTs can be mounted and dismounted within
      few seconds. A novel in situ recalibration method for a simple, quick and more
      accurate calibration of all sensors has been developed. Thermal losses within the
      setup are analysed and are mathematically considered for each measurement. All
      random and systematic errors are encountered for by a MATLAB routine, calculating
      all the target parameters and their uncertainties. The setup provides a
      measurement accuracy of +/-2.34 MUV/K for alpha, +/-810.16 S/m for sigma, +/-0.13
      W/mK for lambda, and +/-0.0075 for ZT at a mean temperature of 42.5  degrees C
      for the specifically designed test samples with a pillar diameter of 696 MUm and
      thickness of 134 MUm, embedded in a polyethylene terephthalate polymer matrix.

PMID- 22852714
TI  - Measurement of thermodiffusion coefficient of hydrocarbon binary mixtures under
      pressure with the thermogravitational technique.
AB  - It was designed and constructed a new thermogravitational column able to operate
      at high pressures (up to 50 MPa). This new thermogravitational column is of the
      cylindrical type with closed ends. It is made of stainless steel. The length of
      the column is 0.5 m and the gap between its two walls is variable. First, the
      column was validated at atmospheric pressure by means of measurements of the
      thermodiffusion coefficient of well-known binary mixtures. Then, this new
      thermogravitational column was used to measure the thermodiffusion coefficient of
      the binary mixtures 1,2,3,4-tetrahydronaphtalene/isobutylbenzene, 1,2,3,4
      tetrahydronaphtalene/n-dodecane, and isobutylbenzene/n-dodecane at high pressures
      and within the pressure range between 0.1 and 20 MPa at a mean temperature of 25 
      degrees C. We have found a linear dependence between the thermodiffusion
      coefficient and the pressure.

PMID- 22852716
TI  - Modeling analysis and experimental study on the optical fiber hydrogen sensor
      based on Pd-Y alloy thin film.
AB  - The failure of hydrogen sensor with palladium film is primarily the phase
      transition of PdH. To restrain this, a novel palladium and yttrium (Pd-Y) alloy
      film was prepared by the co-sputtering method and was used to design an optical
      fiber hydrogen sensor. A sensor model was established based on the optical film
      matrix method. The relationship between the reflectivity of the film and the
      hydrogen concentration was discussed. The experimental results show that this
      sensor is superior to the traditional sensor with Pd in shortening the response
      and recovery time, restraining drift, and promoting repeatability. The Pd-Y alloy
      film is an extremely promising material for detecting hydrogen.

PMID- 22852717
TI  - Incorporation of the stress concentration slots into the flexures for a high
      performance microaccelerometer.
AB  - Presented in this paper is a development of a high-performance piezoresistive
      microaccelerometer based on the slot etching in the quad flexures for the
      vibration detection of high speed spindle. The proposed structure consists of a
      proof mass supported by four thin flexures with slots etched in the middle. Boron
      diffused piezoresistors located near the stress concentration regions are used
      for sensing the localized stress resulting from the incorporation of the slots
      into the flexures. Theoretical analysis and finite element analysis show
      satisfactory results of an improved sensitivity and favorable natural frequency
      higher than 10 kHz, conforming to the initial design requirements. The
      microfabrication techniques are described to prototype the two accelerometer
      chips, one with slots and the other one without slots. The tested
      microaccelerometers with 3 V DC power supply show an average sensitivity of 0.424
      mV/g normal to the proof mass plane, increased by 60.6% than the ones without
      slots. An average transverse sensitivity is found to be 9.2 MUV/g along X axis
      and 14.2 MUV/g along Y axis, either of which is less than 3.5% of prime-axis
      sensitivity. Concerning the resonant frequency, dynamic experiment shows about
      12.46 kHz and is available for the proposed design with a tiny loss of 3.5%
      compared with the quad-beam design. When taking the product of sensitivity and
      natural frequency as judgment criteria, an inspiring increase by 28.6% of the
      figure of merit is accomplished for the proposed accelerometer. Overall, the
      findings of this study confirm the feasibility of incorporating slots into the
      conventional configurations to improve the sensor sensitivity while maintaining a
      comparatively high natural frequency.

PMID- 22852718
TI  - In situ polarized 3He system for the Magnetism Reflectometer at the Spallation
      Neutron Source.
AB  - We report on the in situ polarized (3)He neutron polarization analyzer developed
      for the time-of-flight Magnetism Reflectometer at the Spallation Neutron Source
      at Oak Ridge National Laboratory. Using the spin exchange optical pumping method,
      we achieved a (3)He polarization of 76% +/- 1% and maintained it for the entire
      three-day duration of the test experiment. Based on transmission measurements
      with unpolarized neutrons, we show that the average analyzing efficiency of the
      (3)He system is 98% for the neutron wavelength band of 2-5 A. Using a highly
      polarized incident neutron beam produced by a supermirror bender polarizer, we
      obtained a flipping ratio of >100 with a transmission of 25% for polarized
      neutrons, averaged over the wavelength band of 2-5 A. After the cell was
      depolarized for transmission measurements, it was reproducibly polarized and this
      performance was maintained for three weeks. A high quality polarization analysis
      experiment was performed on a reference sample of Fe/Cr multilayer with strong
      spin-flip off-specular scattering. Using a combination of the position sensitive
      detector, time-of-flight method, and the excellent parameters of the (3)He cell,
      the polarization analysis of the two-dimensional maps of reflected, refracted,
      and off-specular scattered intensity above and below the horizon were obtained,
      simultaneously.

PMID- 22852719
TI  - In situ measurement of alternating current magnetic susceptibility of Pd-hydrogen
      system for determination of hydrogen concentration in bulk.
AB  - An alternating current magnetic susceptometer for use as a hydrogen gauge for
      hydrogen-storage materials was designed and developed. The experimental system
      can simultaneously measure the hydrogen equilibrium pressure and the magnetic
      susceptibility of metal hydrides. The background voltage of the susceptometer was
      stabilized for a long period of time, without any adjustments, by attaching an
      efficient compensation circuit. The performance of the susceptometer at a static
      hydrogen concentration was demonstrated by measuring the magnetic susceptibility
      of a Pd-hydrogen system under equilibrium conditions. The in situ measurement of
      the magnetic susceptibility of Pd during hydrogen absorption was carried out
      using the susceptometer. Since the in situ magnetic susceptibility obtained at a
      lower initial hydrogen pressure agreed with the magnetic susceptibility measured
      at a static hydrogen concentration, the susceptometer could be used to determine
      the hydrogen concentration in Pd in situ. At a higher initial hydrogen pressure,
      enhancement of the magnetic susceptibility was observed at the beginning of
      hydrogen absorption because the magnetic moments induced by the large temporary
      strain generated in the Pd affected the magnetic susceptibility.

PMID- 22852720
TI  - A microcontroller-based lock-in amplifier for sub-milliohm resistance
      measurements.
AB  - This paper presents a novel approach to the design of a digital ohmmeter with a
      resolution of <60 MUOmega based on a general-purpose microcontroller and a high
      impedance instrumentation amplifier only. The design uses two digital I/O-pins to
      alternate the current through the sample resistor and combined with a proper
      firmware routine, the design is a lock-in detector that discriminates any signal
      that is out of phase/frequency with the reference signal. This makes it possible
      to selectively detect the MUV drop across sample resistors down to 55.6 MUOmega
      using only the current that can be supplied by the digital output pins of a
      microcontroller. This is achieved without the need for an external reference
      signal generator and does not rely on the computing processing power of a digital
      signal processor.

PMID- 22852721
TI  - Magnetophoretic trajectory tracking magnetometry: a new technique for assessing
      magnetic properties of submagnetic microparticles and cells.
AB  - We develop a new approach for assessing magnetic properties of submagnetic
      microparticles and cells, magnetophoretic trajectory tracking magnetometry
      (MTTM), that employs recording of long 2D trajectories of particle motion in a
      slot fluid channel caused by the action of crossed gravitational and magnetic
      forces. The studies are focused on the development of theoretical backgrounds of
      the method and evaluation of its uncertainty caused by the mutual hydrodynamic
      entrainment of moving particles. Computerized equipment implementing MTTM
      technique is described and its performance is illustrated. According to our
      studies, the new technique can serve a reliable experimental method with
      analytical qualities.

PMID- 22852722
TI  - High mass resolution time of flight mass spectrometer for measuring products in
      heterogeneous catalysis in highly sensitive microreactors.
AB  - We demonstrate a combined microreactor and time of flight system for testing and
      characterization of heterogeneous catalysts with high resolution mass
      spectrometry and high sensitivity. Catalyst testing is performed in silicon-based
      microreactors which have high sensitivity and fast thermal response. Gas analysis
      is performed with a time of flight mass spectrometer with a modified nude Bayard
      Alpert ionization gauge as gas ionization source. The mass resolution of the time
      of flight mass spectrometer using the ion gauge as ionization source is estimated
      to m/Deltam > 2500. The system design is superior to conventional batch and flow
      reactors with accompanying product detection by quadrupole mass spectrometry or
      gas chromatography not only due to the high sensitivity, fast temperature
      response, high mass resolution, and fast acquisition time of mass spectra but it
      also allows wide mass range (0-5000 amu in the current configuration). As a
      demonstration of the system performance we present data from ammonia oxidation on
      a Pt thin film showing resolved spectra of OH and NH(3).

PMID- 22852723
TI  - Design and construction of a guarded hot plate apparatus operating down to liquid
      nitrogen temperature.
AB  - A double-sided guarded hot plate apparatus (GHP) is specifically designed,
      fabricated, and constructed for the measurement of thermal conductivities of
      insulation specimens operated down to liquid nitrogen temperature (-196  degrees
      C), at different controlled pressures from 0.005 Pa to 0.105 MPa. The specimens
      placed in this apparatus are 300 mm in diameter at various thicknesses ranging
      from 4 mm to 40 mm. The apparatus is different from traditional GHP in terms of
      structure, supporting and heating method. The details of the design and
      construction of the hot plate, the cold plates, the suspensions, the clampings,
      and the vacuum chamber of the system are presented. The measurement methods of
      the temperatures, the input power, the meter area, and the thickness of the
      specimens are given. The apparatus is calibrated with teflon plates as sample and
      the maximum deviation from the published data is about 6% for thermal
      conductivity. The uncertainties for the measurement are also discussed in this
      paper.

PMID- 22852724
TI  - Computational analysis of responses of a wedge-shaped-tip optical fiber probe in
      bubble measurement.
AB  - Optical-fiber probing is widely employed in bubble/droplet measurement in gas
      liquid two-phase flows. Several types of optical fiber probes with a very high
      S/N ratio and high performance have been developed, but further improvement in
      the probes' measurement accuracy and reliability for industrial applications is
      desired. We tried to eliminate optical noise in the probe measurements, and we
      found that the signals include some peak signs that have potential for advanced
      measurement with optical-fiber probing. We developed a ray-tracing numerical
      simulator and identified the mechanisms underlying the generation of the signals.
      In order to numerically simulate the optical probing signals, the simulator must
      use 3D frameworks composed of incident beams, the reflection and refraction on
      the surfaces of the optical elements (i.e., an optical fiber, a sensing tip, an
      air phase, and a water phase), and beams returning from the sensing tip to the
      other tip through the fiber. We used all of these in a simple rendering framework
      based on a ray-tracing algorithm with Fresnel's law, and we observed the
      mechanism of some promising signals that may be useful for extracting the hidden
      potential of optical-fiber probing. To verify the simulator's performance, we
      carried out three comparative experiments with fundamental setups using a wedge
      shaped single-tip optical fiber probe, examining: (1) the beam trajectories and
      energy leaking out from the sensing tip into the surrounding air phase or water
      phase, (2) the probing signals throughout penetration of the sensing tip at the
      air-water free interface in light of the three-dimensional deformation, and (3)
      the probing signals throughout penetration of the sensing tip into a bubble in
      light of the three-dimensional bubble shape. As a result, (a) we found that an
      optical fiber probe with a wedge-shaped tip has particular characteristics of
      beam emissions from the tip, and the emitting angles switched depending on the
      phases covering the tip. This phenomenon is very effective for further advanced
      measurement. (b) We observed numerically that the cutting angle of the sensing
      tip maximizing the air signal level was approximately 30 degrees , and therefore
      this angle is the best for obtaining the highest S/N ratio. (c) We found that the
      meniscus shape clearly affected the probing signal optically. (d) We observed the
      mechanism of a pre-signal caused by the reflection at the frontal and rear
      interfaces of a bubble. The pre-signal is very useful for practical measurement
      because it appears only when the probe penetrates the center region of a bubble.
      We compared the above numerical results with the results of the three
      experiments, and there was satisfactory correspondence between the numerical and
      experimental results.

PMID- 22852725
TI  - 3 MV hypervelocity dust accelerator at the Colorado Center for Lunar Dust and
      Atmospheric Studies.
AB  - A hypervelocity dust accelerator for studying micrometeorite impacts has been
      constructed at the Colorado Center for Lunar Dust and Atmospheric Studies
      (CCLDAS) at the University of Colorado. Based on the Max-Planck-Institut fur
      Kernphysik (MPI-K) accelerator, this accelerator is capable of emitting single
      particles of a specific mass and velocity selected by the user. The accelerator
      consists of a 3 MV Pelletron generator with a dust source, four image charge
      pickup detectors, and two interchangeable target chambers: a large high-vacuum
      test bed and an ultra-high vacuum impact study chamber. The large test bed is a
      1.2 m diameter, 1.5 m long cylindrical vacuum chamber capable of pressures as low
      as 10(-7) torr while the ultra-high vacuum chamber is a 0.75 m diameter, 1.1 m
      long chamber capable of pressures as low as 10(-10) torr. Using iron dust of up
      to 2 microns in diameter, final velocities have been measured up to 52 km/s. The
      spread of the dust particles and the effect of electrostatic focusing have been
      measured using a long exposure CCD and a quartz target. Furthermore, a new
      technique of particle selection is being developed using real time digital
      filtering techniques. Signals are digitized and then cross-correlated with a
      shaped filter, resulting in a suppressed noise floor. Improvements over the MPI-K
      design, which include a higher operating voltage and digital filtering for
      detection, increase the available parameter space of dust emitted by the
      accelerator. The CCLDAS dust facility is a user facility open to the scientific
      community to assist with instrument calibrations and experiments.

PMID- 22852726
TI  - SPHERES, Julich's high-flux neutron backscattering spectrometer at FRM II.
AB  - SPHERES  is a third-generation neutron backscattering spectrometer, located at
      the 20 MW German neutron source FRM II and operated by the Julich Centre for
      Neutron Science. It offers an energy resolution (fwhm) better than 0.65 MUeV, a
      dynamic range of +/- 31 MUeV, and a signal-to-noise ratio of up to 1750:1.

PMID- 22852727
TI  - Microtensile testing of submicrometer thick functional polymer samples.
AB  - Organic electronic devices are currently being introduced in commercial
      applications such as flexible displays. Due to the mechanical loading of these
      devices during bending, it is important to know the mechanical properties in
      order to assess reliability. It is therefore essential to develop experimental
      setups for the mechanical characterization of submicrometer thick functional
      polymer layers. In this paper a new microtensile approach is presented along with
      first results for Young's modulus of polyimide (PI) and the conductive polymer
      PEDOT:PSS obtained using this method. The microtensile specimen are made of a
      bilayer consisting of PI as the substrate layer and of a submicron layer of
      PEDOT:PSS deposited on top of it. The mechanical properties are derived from
      comparison of measurements performed on samples with and without the functional
      layer and by varying this layer's thickness. A thorough error analysis is also
      presented to provide an overview of the precision inherent in this approach. The
      experiments yield Young's moduli of 3.28 +/- 0.34 GPa for PI and of 4.51 +/- 0.34
      GPa for PEDOT:PSS.

PMID- 22852728
TI  - Experimental determination of dielectric barrier discharge capacitance.
AB  - The determination of electrical parameters (such as instantaneous power,
      transferred charge, and gas gap voltage) in dielectric barrier discharge (DBD)
      reactors relies on estimates of key capacitance values. In the classic large
      scale sinusoidal-voltage driven DBD, also known as silent or ozonizer discharge,
      capacitance values can be determined from charge-voltage (Q-V) plot, also called
      Lissajous figure. For miniature laboratory reactors driven by fast pulsed voltage
      waveforms with sub-microsecond rise time, the capacitance of the dielectric
      barriers cannot be evaluated from a single Q-V plot because of the limited
      applicability of the classical theory. Theoretical determination can be
      problematic due to electrode edge effects, especially in the case of asymmetrical
      electrodes. The lack of reliable capacitance estimates leads to a "capacitance
      bottleneck" that obstructs the determination of other DBD electrical parameters
      in fast-pulsed reactors. It is suggested to obtain capacitance of dielectric
      barriers from a plot of the maximal charge versus maximal voltage amplitude
      (Q(max) - V(max) plot) in a manner analogous to the classical approach. The
      method is examined using measurements of current and voltage waveforms of a
      coaxial DBD reactor in argon at 100 mbar driven by square voltage pulses with a
      rise time of 20 ns and with different voltage amplitudes up to 10 kV.
      Additionally, the applicability of the method has been shown for the data
      reported in literature measured at 1 bar of nitrogen-oxygen gas mixtures and
      xenon.

PMID- 22852729
TI  - A compact, low jitter, nanosecond rise time, high voltage pulse generator with
      variable amplitude.
AB  - In this paper, a compact, low jitter, nanosecond rise time, command triggered,
      high peak power, gas-switch pulse generator system is developed for high energy
      physics experiment. The main components of the system are a high voltage
      capacitor, the spark gap switch and R = 50 Omega load resistance built into a
      structure to obtain a fast high power pulse. The pulse drive unit, comprised of a
      vacuum planar triode and a stack of avalanche transistors, is command triggered
      by a single or multiple TTL (transistor-transistor logic) level pulses generated
      by a trigger pulse control unit implemented using the 555 timer circuit. The
      control unit also accepts user input TTL trigger signal. The vacuum planar triode
      in the pulse driving unit that close the first stage switches is applied to drive
      the spark gap reducing jitter. By adjusting the charge voltage of a high voltage
      capacitor charging power supply, the pulse amplitude varies from 5 kV to 10 kV,
      with a rise time of <3 ns and the maximum peak current up to 200 A (into 50
      Omega). The jitter of the pulse generator system is less than 1 ns. The maximum
      pulse repetition rate is set at 10 Hz that limited only by the gas-switch and
      available capacitor recovery time.

PMID- 22852730
TI  - High-speed thermo-microscope for imaging thermal desorption phenomena.
AB  - In this work, we describe a thermo-microscope imaging system that can be used to
      visualize atmospheric pressure thermal desorption phenomena at high heating rates
      and frame rates. This versatile and portable instrument is useful for studying
      events during rapid heating of organic particles on the microscopic scale. The
      system consists of a zoom lens coupled to a high-speed video camera that is
      focused on the surface of an aluminum nitride heating element. We leverage high
      speed videography with oblique incidence microscopy along with forward and back
      scattered illumination to capture vivid images of thermal desorption events
      during rapid heating of chemical compounds. In a typical experiment, particles of
      the material of interest are rapidly heated beyond their boiling point while the
      camera captures images at several thousand frames/s. A data acquisition system,
      along with an embedded thermocouple and infrared pyrometer are used to measure
      the temperature of the heater surface. We demonstrate that, while a typical
      thermocouple lacks the response time to accurately measure temperature ramps that
      approach 150  degrees C/s, it is possible to calibrate the system by using a
      combination of infrared pyrometry, melting point standards, and a thermocouple.
      Several examples of high explosives undergoing rapid thermal desorption are also
      presented.

PMID- 22852731
TI  - Development of a quasi-adiabatic calorimeter for the determination of the water
      vapor pressure curve.
AB  - Progress in the knowledge of the water saturation curve is required to improve
      the accuracy of the calibrations in humidity. In order to achieve this objective,
      the LNE-CETIAT and the LNE-CNAM have jointly built a facility dedicated to the
      measurement of the saturation vapor pressure and temperature of pure water. The
      principle is based on a static measurement of the pressure and the temperature of
      pure water in a closed, temperature-controlled thermostat, conceived like a quasi
      adiabatic calorimeter. A copper cell containing pure water is placed inside a
      temperature-controlled copper shield, which is mounted in a vacuum-tight
      stainless steel vessel immersed in a thermostated bath. The temperature of the
      cell is measured with capsule-type standard platinum resistance thermometers,
      calibrated with uncertainties below the millikelvin. The vapor pressure is
      measured by calibrated pressure sensors connected to the cell through a pressure
      tube whose temperature is monitored at several points. The pressure gauges are
      installed in a thermostatic apparatus ensuring high stability of the pressure
      measurement and avoiding any condensation in the tubes. Thanks to the employment
      of several technical solutions, the thermal contribution to the overall
      uncertainty budget is reduced, and the remaining major part is mainly due to
      pressure measurements. This paper presents a full description of this facility
      and the preliminary results obtained for its characterization.

PMID- 22852732
TI  - A simply constructed but efficacious shock tester for high-g level shock
      simulation.
AB  - A simply constructed shock tester, different from existing drop table machines,
      is developed for high-g level shock environment simulation. The theoretical
      model, structure design, and working principle of the drop tester are described.
      A prototype device is set up, where a carbon fiber reinforced polymer with a high
      specific modulus is used. Using a Bruel & Kjaer high-g accelerometer, experiments
      to verify the validity of the design are carried out and results are given. The
      maximum acceleration level is in excess of 60,000 g, limited only by the manual
      driving force.

PMID- 22852733
TI  - A novel method for effective sodium ion implantation into silicon.
AB  - Although sodium ion implantation is useful to the surface modification of
      biomaterials and nano-electronic materials, it is a challenging to conduct
      effective sodium implantation by traditional implantation methods due to its high
      chemical reactivity. In this paper, we present a novel method by coupling a Na
      dispenser with plasma immersion ion implantation and radio frequency discharge. X
      ray photoelectron spectroscopy (XPS) depth profiling reveals that sodium is
      effectively implanted into a silicon wafer using this apparatus. The Na 1s XPS
      spectra disclose Na(2)O-SiO(2) bonds and the implantation effects are confirmed
      by tapping mode atomic force microscopy. Our setup provides a feasible way to
      conduct sodium ion implantation effectively.

PMID- 22852734
TI  - High temperature Z-meter setup for characterizing thermoelectric material under
      large temperature gradient.
AB  - To properly estimate a thermoelectric material's performance, one should be able
      to characterize a single thermoelectric (TE) element with a large temperature
      gradient. In this work, we present an experimental setup including a Z-meter that
      can heat the sample to a very high temperature of 1200  degrees C in vacuum. The
      Z-meter can simultaneously measure all three thermoelectric parameters (Seebeck
      coefficient, thermal conductivity, and electrical conductivity), as well as
      measure the generated power and the efficiency for a single TE leg. Furthermore,
      this measurement of power conversion efficiency is used to generate a measure of
      the material's ZT. An in situ metallurgical bond was used to achieve low thermal
      (0.05 Kcm(2)/W) and electrical (3 mOmega) contact parasitics. An integrated
      strain gauge ensures reproducible thermal contact. At high temperature (>600 K),
      radiative heat transfer is modeled and the instrument is optimized to suppress
      the systematic error to below 7%. The TE parameters and ZT for a bulk-sample
      (Bi(2)Te(3)) and a thin-film sample (ErAs:InGaAlAs) with a large temperature
      gradient (DeltaT ~ 200 K) have been measured and are within 3%-7% of the
      independently measured values.

PMID- 22852735
TI  - Accurate measurements of water vapor transmission through high-performance
      barrier layers.
AB  - We report a new approach to measuring very low rates of water vapor transmission
      through high-performance barrier layers, based on detection of the water vapor by
      cavity ring-down infrared spectroscopy. It provides accurate and traceable
      measurements with a detection limit for water vapor transmission significantly
      below 1 * 10(-4) g/m(2)/day. The system is underpinned by dynamic reference
      standards of water vapor generated between 5 and 2000 nmol/mol with an estimated
      relative expanded uncertainty of +/-2%. It has been compared with other methods
      and demonstrates good comparability.

PMID- 22852736
TI  - Note: Tesla transformer damping.
AB  - Unexpected heavy damping in the two winding Tesla pulse transformer is shown to
      be due to small primary inductances. A small primary inductance is a necessary
      condition of operability, but is also a refractory inefficiency. A 30%
      performance loss is demonstrated using a typical "spiral strip" transformer. The
      loss is investigated by examining damping terms added to the transformer's
      governing equations. A significant alteration of the transformer's architecture
      is suggested to mitigate these losses. Experimental and simulated data comparing
      the 2 and 3 winding transformers are cited to support the suggestion.

PMID- 22852737
TI  - Note: pneumatically modulated liquid delivery with feedback control.
AB  - We present the design and characterization of a pneumatically driven liquid
      delivery system using an embedded microcontroller with feedback control capable
      of maintaining a stable, constant flow rate over several hours of operation. Flow
      rates with relative standard deviations less than 1% were achieved and compared
      to a typical laboratory syringe pump.

PMID- 22852738
TI  - Note: effect of the tilting angle of the wire on the onset of natural convection
      in the transient hot wire method.
AB  - In this paper, numerical and experimental investigations are systematically
      performed to identify the effect of the tilting angle of the wire on the onset of
      natural convection in the transient hot wire method (THWM), a widely accepted
      technique for measuring the thermal conductivity of various media, especially
      nanofluids. To validate our numerical simulation code, the numerical results are
      compared with theoretical solutions as well as with experimental results. Based
      on the results, we show that the onset time of natural convection in THWM
      decreases rapidly with the increase of the wire's tilting angle from vertical
      position. Also, we systematically show the effect of the wire's tilting angle on
      the linear region, which is a suitable measurement interval, and on the
      measurement error of THWM.

PMID- 22852739
TI  - Note: utilizing Pb(Zr(0.95)Ti(0.05))O3 ferroelectric ceramics to scale down
      autonomous explosive-driven shock-wave ferroelectric generators.
AB  - Further miniaturization of recently designed autonomous ferroelectric generators
      (FEGs) [S. I. Shkuratov, J. Baird, and E. F. Talantsev, Rev. Sci. Instrum. 82,
      086107 (2011)], which are based on the effect of explosive-shock-wave
      depolarization of poled ferroelectrics is achieved. The key miniaturization
      factor was the utilization of high-energy density Pb(Zr(0.95)Ti(0.05))O(3) (PZT
      95/5) ferroelectric ceramics as energy-carrying elements of FEGs instead of the
      previously used Pb(Zr(0.52)Ti(0.48))O(3) (PZT 52/48). A series of experiments
      demonstrated that FEGs based on smaller PZT 95/5 ferroelectric elements are
      capable of producing the same output voltage as those based on PZT 52/48 elements
      twice as large. It follows from the experimental results that the FEG output
      voltage is directly proportional to the thickness of PZT 95/5 samples. A
      comparison of the operation of FEGs based on PZT 95/5 and on PZT 52/48
      ferroelectrics is presented.

PMID- 22852740
TI  - Note: electrical and thermal characterization of a ferroelectric thin film with
      an electro-thermal nanoprobe.
AB  - The localized temperature-dependent piezoelectric response of ferroelectric
      barium strontium titanate (BST) thin films is studied using an electro-thermal
      (ET) nanoprobe. The ET probe provides independent electrical and thermal
      excitation to a nanometer-scale volume of the specimen and is capable of
      detecting the phase transition temperature of the BST thin films. The
      piezoresponse measured by the ET probe follows the temperature dependence of the
      piezoelectric constant, whereas with bulk heating the response follows the
      temperature dependence of the spontaneous polarization. The observed differences
      stem from the localized inhomogeneous electro-thermal field distribution at the
      specimen.

PMID- 22852741
TI  - Note: in vivo pH imaging system using luminescent indicator and color camera.
AB  - Microscopic in vivo pH imaging system is developed that can capture the
      luminescent- and color-imaging. The former gives a quantitative measurement of a
      pH distribution in vivo. The latter captures the structural information that can
      be overlaid to the pH distribution for correlating the structure of a specimen
      and its pH distribution. By using a digital color camera, a luminescent image as
      well as a color image is obtained. The system uses HPTS (8-hydroxypyrene-1,3,6
      trisulfonate) as a luminescent pH indicator for the luminescent imaging. Filter
      units are mounted in the microscope, which extract two luminescent images for
      using the excitation-ratio method. A ratio of the two images is converted to a pH
      distribution through a priori pH calibration. An application of the system to
      epidermal cells of Lactuca Sativa L is shown.

PMID- 22852742
TI  - Note: grazing incidence small and wide angle x-ray scattering combined with
      imaging ellipsometry.
AB  - The combination of grazing incidence small angle x-ray scattering (GISAXS) and
      grazing incidence wide angle x-ray scattering (GIWAXS) with optical imaging
      ellipsometry is presented as an upgrade of the available measurement techniques
      at the wiggler beamline BW4 of the Hamburger Synchrotronstrahlungslabor. The
      instrument is introduced with the description of the alignment procedure to
      assure the measurement of imaging ellipsometry and GISAXS/GIWAXS on the same
      sample spot. To demonstrate the possibilities of the new instrument examples of
      morphological investigation on films made of poly(3-hexylthiophene) and [6,6]
      phenyl-C(61) butyric acid methyl ester as well as textured poly(9,9
      dioctylfluorene-alt-benzo-thia-diazole) are shown.

PMID- 22852743
TI  - Note: low temperature superconductor superconducting quantum interference device
      system with wide pickup coil for detecting small metallic particles.
AB  - A one-channel low temperature superconductor superconducting quantum interference
      device system comprising a second-order axial gradiometer with a sensing area of
      10 mm * 190 mm was developed. The gradiometer was mounted in a liquid-helium
      dewar (450-mm diameter; 975-mm length), with a gap of 12 mm between the pickup
      coil and the dewar-tail surface. The magnetic field sensitivity was measured to
      be 16 fT/Hz(1/2) in the white noise regime above 2 Hz. The system was used to
      measure stainless steel particles of different sizes passing through the sensing
      area. A 100-MUm diameter SUS304 particle was readily detected passing at
      different positions underneath the large pickup coil by measuring its 1.3-pT
      magnetic field. Thus, the system was shown to be applicable to quality control of
      lamination sheet products such as lithium ion batteries.

PMID- 22852746
TI  - Adiponectin is an independent predictor of tissue plasminogen activator levels in
      patients under haemodialysis.
AB  - OBJECTIVE: The aim of this study was to evaluate the association of tissue-type
      plasminogen activator (t-PA) levels with clinical data of patients under
      haemodialysis (HD) and with several variables potentially related to endothelial
      function and dysfunction. MATERIAL AND METHODS: In a cross-sectional study
      involving 189 Portuguese HD patients, circulating levels of t-PA, lipids,
      oxidized low-density lipoprotein (Ox-LDL), interleukin-6 (IL-6), C-reactive
      protein (CRP), adiponectin, plasminogen activator inhibitor type 1 (PAI-1) and
      fibrin fragment D-dimer were measured. RESULTS: Considering the entire
      population, t-PA correlated inversely and significantly with adiponectin and high
      density lipoprotein-cholesterol, and positively and significantly with age, body
      mass index, PAI-1, IL-6, CRP, D-dimer, cholesterol and Ox-LDL. In multiple linear
      regression analysis PAI-1, age and adiponectin remained statistically associated
      with t-PA values (p < 0.01 for all). The weakest significant association (p =
      0.046) was that found between t-PA and D-dimer. CONCLUSION: Adiponectin is a main
      determinant of t-PA level, which may be a good marker of endothelial dysfunction
      in HD patients.

PMID- 22852747
TI  - Radon emissions related to the granitic Precambrian shield in southern Brazil.
AB  - The equivalent uranium (eU) activity concentration was analysed in selected
      granite samples at several sites in Porto Alegre, Southern Brazil, to obtain
      information on the radon ((222)Rn) generation by the aquifer rock matrices. Radon
      analyses of ground water and soil samples were also performed. Several samples
      exhibited a dissolved (222)Rn activity concentration exceeding the World Health
      Organization maximum limit of 100 Bq l(-1). The dissolved radon content in ground
      waters from the Fractured Precambrian Aquifer System exhibited a direct
      significant correlation with the eU in the rock matrices, which is a typical
      result of water-rock interactions. Variation in the soil's porosity was confirmed
      as an important factor for (222)Rn release, as expected, due to its gaseous
      nature. Thus, although the calcic-alkaline to alkaline Precambrian granitoid
      rocks of the study area are important reservoirs for underground resources, they
      can release high amounts of radon gas into the liquid phase.

PMID- 22852748
TI  - Development and validation of the short form of the Brief Cognitive Assessment
      Tool (BCAT-SF).
AB  - This article describes the development and validation of a short form of the
      Brief Cognitive Assessment Tool (BCAT), the BCAT-SF. Frontline providers and many
      specialists report having little time to assess cognitive functioning, despite
      recognizing the utility of doing so. Many of the screening tools now available
      are judged to require too much time to administer. With this in mind, our intent
      was to design a very brief measure that retained much of the excellent
      psychometric properties of the original 21-item BCAT. We present a comparison of
      the evidence for the reliability and validity of the scores from the original and
      short forms of the BCAT. One hundred four older adults referred for
      neuropsychological evaluation participated in the study. We used a rational
      approach to select items from the original BCAT to create the BCAT-SF. To ensure
      content validity, the six items selected represented the cognitive domains of
      contextual memory, executive functioning, and attention. Psychometric analyses
      confirmed strong evidence of reliability, construct validity, and predictive
      validity. The BCAT-SF differentiated between mild cognitive impairment and
      dementia with a sensitivity of 0.90, a specificity of 0.81, and an area under the
      receiver operating characteristic curve of 0.93. Furthermore, the BCAT-SF
      predicted instrumental and basic activities of daily living. The BCAT-SF can be
      administered in three to four minutes, is easily administered (by provider or
      technician), and is cost-effective. In addition, preliminary evidence finds the
      BCAT-SF to be psychometrically robust.

PMID- 22852749
TI  - Liposome-gold nanorod hybrids for high-resolution visualization deep in tissues.
AB  - The design of liposome-nanoparticle hybrids offers a rich toolbox for the
      fabrication of multifunctional modalities. A self-assembled liposome-gold nanorod
      hybrid vesicular system that consists of lipid-bilayer-associated gold nanorods
      designed to allow deep tissue detection, therapy, and monitoring in living
      animals using multispectral optoacoustic tomography has been fabricated and
      characterized in vitro and in vivo.

PMID- 22852750
TI  - The Microsporum canis genome is organized into five chromosomes based on evidence
      from electrophoretic karyotyping and chromosome end mapping.
AB  - The karyotype of Microsporum canis was analyzed by contoured-clamped homogeneous
      electric field (CHEF) gel electrophoresis. Four chromosomal bands that correspond
      to five chromosomes ranging from 3.0-6.2 Mb were identified, adding the total
      genome size to approximately 24.9 Mb. To confirm the number of chromosomes in M.
      canis, the number of telomeres was assessed by using a telomeric probe
      (TTAGGG)(4) in Southern blot analyses of digested genomic DNA. Treatment of M.
      canis DNA with Bal31 exonuclease revealed progressive shortening of the DNA
      fragments positive for the (TTAGGG)(4) sequence, supporting location of repeats
      at the chromosome ends. These results can aid in improving the understanding of
      the genetic characterization of M. canis and the molecular epidemiology of
      dermatophytoses caused by this fungus.

PMID- 22852751
TI  - Study of the epidemiology of Pneumocystis carinii f. sp. suis in abattoir swine
      in Portugal.
AB  - Pneumocystis has been identified in various mammalian species, including
      domestic, wild and zoo animals. This study's main objectives were: (1) to
      estimate the prevalence of the Pneumocystis carinii f. sp. suis infection in
      slaughtered pigs in Portugal, (2) assess the prevalence differences within
      distinct age groups of animals, (3) determine the possible associations between
      pulmonary lesions and the infection, and (4) genetically characterize the P.
      carinii f. sp. suis isolates recovered from infected animals using PCR with DNA
      sequencing. An epidemiological cross-sectional study was conducted using 215 pig
      lung tissue samples which demonstrated a global prevalence of 7% (14 positive
      samples). This value was later validated by statistical analysis as being
      representative of the national population prevalence. Regarding the assessment of
      relations between the different variables investigated during the study (age,
      gender, geographical region, type of farming, weight and pulmonary lesion) and
      the P. carinii f. sp. suis infection, no significant statistical differences were
      found, and apparently, no predisposing factors could be defined. Nevertheless,
      infection by Pneumocystis in pigs is ubiquitous and it can be detected in healthy
      animals. Thus, the colonization of P. carinii f. sp. suis among healthy
      individuals suggests that asymptomatic carriers can be an effective reservoir for
      susceptible animals and participate in the transmission of infection. The present
      data confirmed that porcine Pneumocystis is genetically distinct from
      Pneumocystis DNA detected in other mammalian hosts.

PMID- 22852752
TI  - Isolation and characterization of a new fungal genus and species, Aphanoascella
      galapagosensis, from carapace keratitis of a Galapagos tortoise (Chelonoidis
      nigra microphyes).
AB  - A new fungal genus and species, Aphanoascella galapagosensis, recovered from
      carapace keratitis in a Galapagos tortoise residing in a south Texas zoological
      collection, is characterized and described. The presence of a pale peridium
      composed of textura epidermoidea surrounded by scarce Hulle cell-like
      chlamydospores, and the characteristic reticulate ascospores with an equatorial
      rim separates it from other genera within the Onygenales. The phylogenetic tree
      inferred from the analysis of D1/D2 sequences demonstrates that this fungus
      represents a new lineage within that order. As D1/D2 and ITS sequence data also
      shows a further separation of Aphanoascus spp. into two monophyletic groups, we
      propose to retain the generic name Keratinophyton for species whose ascospores
      are pitted and display a conspicuous equatorial rim, and thereby propose new
      combinations in this genus for four Aphanoascus species.

PMID- 22852753
TI  - Crystal structure of firefly luciferase in a second catalytic conformation
      supports a domain alternation mechanism.
AB  - Beetle luciferases catalyze a two-step reaction that includes the initial
      adenylation of the luciferin substrate, followed by an oxidative decarboxylation
      that ultimately produces light. Evidence for homologous acyl-CoA synthetases
      supports a domain alternation catalytic mechanism in which these enzymes' C
      terminal domain rotates by ~140 degrees  to adopt two conformations that are used
      to catalyze the two partial reactions. While many structures exist of acyl-CoA
      synthetases in both conformations, to date only biochemical evidence supports
      domain alternation with luciferase. We have determined the structure of a cross
      linked luciferase enzyme that is trapped in the second conformation. This new
      structure supports the role of the second catalytic conformation and provides
      insights into the biochemical mechanism of the luciferase oxidative step.

PMID- 22852754
TI  - "We are all there silently coping." The hidden experiences of parents of adults
      with Asperger syndrome.
AB  - BACKGROUND: The experiences of older parents of adults with Asperger syndrome
      have not been explored in the research literature. METHOD: Four families who had
      middle-aged offspring with Asperger syndrome were interviewed (3 mothers and 1
      couple), and the interviews were analysed using interpretative phenomenological
      analysis (IPA). RESULTS: Six themes emerged from the analysis: (a) providers of
      "hidden" support, (b) role of advocate, (c) social isolation, (d) intrafamilial
      relationships, (e) support for parents, and (f) future concerns. CONCLUSIONS: The
      findings of this study offer insight into the experience of parents of adult sons
      with Asperger syndrome. Implications for future support interventions and
      research are suggested.

PMID- 22852755
TI  - Atmospheric reactive nitrogen in China: sources, recent trends, and damage costs.
AB  - Human activities have intensely altered the global nitrogen cycle and produced
      nitrogenous gases of environmental significance, especially in China where the
      most serious atmospheric nitrogen pollution worldwide exists. We present a
      comprehensive assessment of ammonia (NH(3)), nitrogen oxides (NO(x)), and nitrous
      oxide (N(2)O) emissions in China based on a full cycle analysis. Total reactive
      nitrogen (Nr) emission more than doubled over the past three decades, during
      which the trend of increase slowed for NH(3) emissions after 2000, while the
      trend of increase continued to accelerate for NO(x) and N(2)O emissions. Several
      hotspots were identified, and their Nr emissions were about 10 times higher than
      others. Agricultural sources take 95% of total NH(3) emission; fossil fuel
      combustion accounts for 96% of total NO(x) emission; agricultural (51%) and
      natural sources (forest and surface water, 39%) both contribute to the N(2)O
      emission in China. Total atmospheric Nr emissions related health damage in 2008
      in China reached US$19-62 billion, accounting for 0.4-1.4% of China's gross
      domestic product, of which 52-60% were from NH(3) emission and 39-47% were from
      NO(x) emission. These findings provide policy makers an integrated view of Nr
      sources and health damage to address the significant challenges associated with
      the reduction of air pollution.

PMID- 22852756
TI  - Iodine(III)-mediated tandem oxidative cyclization for construction of 2
      nitrobenzo[b]furans.
AB  - Various 3-alkyl-2-nitrobenzo[b]furans were synthesized from common intermediate 2
      (2-nitroethyl)phenols via a hypervalent iodine-induced oxidative cyclization,
      with good to excellent yields. This facile route is able to efficiently
      functionalize 2-nitrobenzo[b]furans, which are difficult to obtain by classical
      methods.

PMID- 22852757
TI  - Slow-release RGD-peptide hydrogel monoliths.
AB  - We report on the formation of hydrogel monoliths formed by functionalized peptide
      Fmoc-RGD (Fmoc: fluorenylmethoxycarbonyl) containing the RGD cell adhesion
      tripeptide motif. The monolith is stable in water for nearly 40 days. The gel
      monoliths present a rigid porous structure consisting of a network of peptide
      fibers. The RGD-decorated peptide fibers have a beta-sheet secondary structure.
      We prove that Fmoc-RGD monoliths can be used to release and encapsulate material,
      including model hydrophilic dyes and drug compounds. We provide the first insight
      into the correlation between the absorption and release kinetics of this new
      material and show that both processes take place over similar time scales.

PMID- 22852758
TI  - Space-relevant radiation modifies cytokine profiles, signaling proteins and
      Foxp3+ T cells.
AB  - PURPOSE: The major goal was to evaluate effects of various radiation regimens on
      leukocyte populations relatively long-term after whole-body irradiation.
      MATERIALS AND METHODS: C57BL/6 mice were exposed to-low-dose/low-dose rate (LDR)
      (57)Co gamma-rays (0.01 Gy, 0.03 cGy/h), with and without acute 2 Gy proton (1
      Gy/min) or gamma-ray (0.9 Gy/min) irradiation; analyses were done on days 21 and
      56 post-exposure. RESULTS: Numerous radiation-induced changes were noted at one
      or both time points. Among the most striking differences (P < 0.05) were: (i)
      High percentage of CD4(+)CD25(+)Foxp3(+) T cells in spleens from the Proton vs.
      LDR, Gamma and LDR + Proton groups (day 56); (ii) high interleukin-2 (IL-2) in
      spleen supernatants from the LDR and LDR + Proton groups vs. 0 Gy (day 56),
      whereas IL-10 was high in the LDR + Gamma group vs. 0 Gy (day 56); (iii)
      difference in transforming growth factor-beta1 (TGF-beta1) in spleen supernatants
      from Proton and LDR + Proton groups vs. Gamma and LDR + Gamma groups (both days);
      (iv) low TGF-beta1 in blood from LDR + Proton vs. LDR + Gamma group (day 21); and
      (v) high level of activated cJun N-terminal kinase (JNK) in CD4(+) T cells from
      LDR + Proton vs. LDR + Gamma group (day 21). CONCLUSIONS: The findings
      demonstrate that at least some immune responses to acute 2 Gy radiation were
      dependent on radiation quality time of assessment, and pre-exposure to LDR gamma
      rays.

PMID- 22852759
TI  - A furantaxane with an unusual 6/8/6/5 ring system and potent tumor MDR reversal
      activity obtained via microbial transformation.
AB  - A furantaxane (4) with an unusual 6/8/6/5 ring system and two hydroxylated
      products (2, 3) were isolated following the biotransformation of a taxane (1) by
      Streptomyces griseus. The structures of the isolates were elucidated by
      spectroscopic analysis. The absolute configuration of 4, which exhibited potent
      reversal activity in the A549/taxol MDR tumor cell line, was unambiguously
      deduced by single-crystal X-ray diffraction.

PMID- 22852760
TI  - Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected
      Kenyan women receiving valacyclovir.
AB  - Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces
      HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune
      activation. We measured T cell immune activation markers among women
      participating in a randomized placebo-controlled trial of valacyclovir to reduce
      HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with
      lower HIV-1 RNA levels, the distribution of both CD4(+) and CD8(+) CD38(+)HLA
      DR(+) T cells was not different among women taking valacyclovir when compared to
      women taking placebo. Further study is needed to understand the mechanism of HIV
      1 RNA reduction following herpes suppression among those coinfected with HIV-1
      and HSV-2.

PMID- 22852761
TI  - Implications of hybridisation and cytotypic differentiation in speciation
      assessed by AFLP and plastid haplotypes--a case study of Potentilla alpicola La
      Soie.
AB  - BACKGROUND: Hybridisation is presumed to be an important mechanism in plant
      speciation and a creative evolutionary force often accompanied by
      polyploidisation and in some cases by apomixis. The Potentilla collina group
      constitutes a particularly suitable model system to study these phenomena as it
      is morphologically extensively variable, exclusively polyploid and expresses
      apomixis. In the present study, the alpine taxon Potentilla alpicola has been
      chosen in order to study its presumed hybrid origin, identify underlying
      evolutionary processes and infer the discreteness or taxonomic value of hybrid
      forms. RESULTS: Combined analysis of AFLP, cpDNA sequences and ploidy level
      variation revealed a hybrid origin of the P. alpicola populations from South
      Tyrol (Italy) resulting from crosses between P. pusilla and two cytotypes of P.
      argentea. Hybrids were locally sympatric with at least one of the parental forms.
      Three lineages of different evolutionary origin comprising two ploidy levels were
      identified within P. alpicola. The lineages differed in parentage and the
      complexity of the evolutionary process. A geographically wide-spread lineage thus
      contrasted with locally distributed lineages of different origins. Populations of
      P. collina studied in addition, have been regarded rather as recent derivatives
      of the hexaploid P. argentea. The observation of clones within both P. alpicola
      and P. collina suggested a possible apomictic mode of reproduction. CONCLUSIONS:
      Different hybridisation scenarios taking place on geographically small scales
      resulted in viable progeny presumably stabilised by apomixis. The case study of
      P. alpicola supports that these processes played a significant role in the
      creation of polymorphism in the genus Potentilla. However, multiple origin of
      hybrids and backcrossing are considered to produce a variety of evolutionary
      spontaneous forms existing aside of reproductively stabilised, established
      lineages.

PMID- 22852762
TI  - Supporting parents of preschool children in adopting a healthy lifestyle.
AB  - BACKGROUND: Childhood obesity is a public health epidemic. In Canada 21.5% of
      children aged 2-5 are overweight, with psychological and physical consequences
      for the child and economic consequences for society. Parents often do not view
      their children as overweight. One way to prevent overweight is to adopt a healthy
      lifestyle (HL). Nurses with direct access to young families could assess
      overweight and support parents in adopting HL. But what is the best way to
      support them if they do not view their child as overweight? A better
      understanding of parents' representation of children's overweight might guide the
      development of solutions tailored to their needs. METHODS/DESIGN: This study uses
      an action research design, a participatory approach mobilizing all stakeholders
      around a problem to be solved. The general objective is to identify, with nurses
      working with families, ways to promote HL among parents of preschoolers. Specific
      objectives are to: 1) describe the prevalence of overweight in preschoolers at
      vaccination time; 2) describe the representation of overweight and HL, as
      reported by preschoolers' parents; 3) explore the views of nurses working with
      young families regarding possible solutions that could become a clinical tool to
      promote HL; and 4) try to identify a direction concerning the proposed strategies
      that could be used by nurses working with this population. First, an
      epidemiological study will be conducted in vaccination clinics: 288 4-5-year-olds
      will be weighed and measured. Next, semi-structured interviews will be conducted
      with 20 parents to describe their representation of HL and their child's weight.
      Based on the results from these two steps, by means of a focus group nurses will
      identify possible strategies to the problem. Finally, focus groups of parents,
      then nurses and finally experts will give their opinions of these strategies in
      order to find a direction for these strategies. Descriptive and correlational
      statistical analyses will be done on the quantitative survey data using SPSS.
      Qualitative data will be analyzed using Huberman and Miles' (2003) approach.
      NVivo will be used for the analysis and data management. DISCUSSION: The
      anticipated benefits of this rigorous approach will be to identify and develop
      potential intervention strategies in partnership with preschoolers' parents and
      produce a clinical tool reflecting the views of parents and nurses working with
      preschoolers' parents.

PMID- 22852763
TI  - Risk factors of heavy episodic drinking among Korean adolescents.
AB  - The main objective of this study was to identify the risk factors and develop a
      decision tree model of heavy episodic drinking (HED) among adolescents. Data were
      obtained from a representative nationwide Korean population. Nine variables (such
      as last 30 days smoking, school grade, sex, depression, school achievement, level
      of stress, region, and economic status) were found as risk factors of HED. On the
      highest level of the tree root, major classification rule was played by dividing
      based on the last 30 days smoking and school grades. These findings should be
      helpful for school and mental healthcare providers to detect Korean adolescents
      with high possibility of HED, which will aid in planning of healthcare
      interventions for at-risk adolescents.

PMID- 22852765
TI  - Centrally necrotizing breast carcinoma: a rare histological subtype, which was
      cause of misdiagnosis in an evident clinical local recurrence.
AB  - Centrally necrotizing carcinoma is a rare subtype of breast carcinoma, which is
      characterized by an extensive central necrotic zone accounting for at least 70%
      of the cross-sectional area of the neoplasm. This central necrotic zone, in turn,
      is surrounded by a narrow rim of proliferative viable tumor cells. We report an
      unusual clinical situation in which a patient whose evident breast mass suggested
      an ipsilateral local recurrence and for which numerous attempts to confirm the
      histological diagnosis had failed. The patient was treated with a radical
      mastectomy based on clinical suspicion of breast cancer recurrence after an
      undesirable delay. In this case, the narrow rim of viable malignant tissue had a
      thickness of 0.5 to 8 mm, and the centrally necrotizing carcinoma had a central
      zone with a predominance of fibrosis. The special features of this case led to a
      misdiagnosis and to an evident clinical local recurrence.

PMID- 22852764
TI  - Stereotactic body radiation therapy for abdominal oligometastases: a biological
      and clinical review.
AB  - Advances in imaging and biological targeting have led to the development of
      stereotactic body radiation therapy (SBRT) as an alternative treatment of
      extracranial oligometastases. New radiobiological concepts, such as ceramide
      induced endothelial apoptosis after hypofractionated high-dose SBRT, and the
      identification of patients with oligometastatic disease by microRNA expression
      may yet lead to further developments. Key factors in SBRT are delivery of a high
      dose per fraction, proper patient positioning, target localisation, and
      management of breathing-related motion. Our review addresses the radiation doses
      and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland
      oligometastases and treatment outcomes. Reported local control (LC) rates for
      liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 
      100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal
      LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are
      rare. SBRT of adrenal gland oligometastases shows promising results in the case
      of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe
      and effective treatment option for abdominal oligometastases.

PMID- 22852767
TI  - Critical COPD respiratory illness is linked to increased transcriptomic activity
      of neutrophil proteases genes.
AB  - BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral
      blood has shown that this is a very useful approach for biomarker discovery and
      for studying molecular pathogenesis of prevalent diseases. While there is limited
      literature available on gene expression markers associated with Chronic
      Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with
      critical respiratory illness in this disease is not known at the present moment.
      FINDINGS: By using Agilent microarray chips, we have profiled gene expression
      signatures in the whole blood of 28 COPD patients hospitalized with different
      degrees of respiratory compromise.12 of them needed of admission to the ICU,
      whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0
      software was used for performing statistical comparisons of transcript levels
      between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the
      Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and
      visualize genes by function and pathway (gene ontology). T-test showed evidence
      of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and
      KEGG analysis of the most representative biological functions revealed that ICU
      patients had increased levels of neutrophil gene transcripts, being [cathepsin G
      (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)],
      [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil
      specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability
      increasing protein (BPI)] the most representative ones. Proteins codified by
      these genes form part of the azurophilic granules of neutrophils and are involved
      in both antimicrobial defence and tissue damage. This "neutrophil signature" was
      paralleled by the necessity of advanced respiratory and vital support, and the
      presence of bacterial infection. CONCLUSION: Study of transcriptomic signatures
      in blood suggests an essential role of neutrophil proteases in COPD patients with
      critical respiratory illness. Measurement and modulation of the expression of
      these genes could present an option for clinical monitoring and treatment of
      severe COPD exacerbations.

PMID- 22852768
TI  - Overview of the Consortium of Hospitals Advancing Research on Tobacco (CHART).
AB  - BACKGROUND: The Consortium of Hospitals Advancing Research on Tobacco (CHART) is
      a network of six projects and a research coordinating unit funded by the National
      Heart, Lung, and Blood Institute, the National Cancer Institute, the National
      Institute on Drug Abuse, and the National Institutes of Health (NIH) Office of
      Behavioral and Social Science Research. The CHART projects will assess the
      effectiveness and cost-effectiveness of smoking cessation interventions initiated
      during hospitalization and continued post-discharge. METHODS/DESIGN: Along with a
      seventh project funded previously under the NIH Challenge grants, the CHART
      projects will assess smoking cessation strategies delivered to approximately
      10,000 hospitalized smokers across a geographically diverse group of nearly 20
      private, public, academic, and community hospitals. The CHART research
      coordinating unit at Kaiser Permanente Center for Health Research provides
      organizational and data coordination support, facilitating the development of
      common measures for combining data from multiple CHART projects. DISCUSSION: The
      targeted enrollment in CHART, if achieved, will represent the largest, most
      diverse pooled dataset of hospitalized smokers receiving smoking cessation
      assistance, and is designed to contribute to the dissemination and implementation
      of smoking cessation interventions provided by hospital systems.

PMID- 22852772
TI  - Discovery of a metalloenzyme-like cooperative catalytic system of metal
      nanoclusters and catechol derivatives for the aerobic oxidation of amines.
AB  - We have discovered a new class of cooperative catalytic system, consisting of
      heterogeneous polymer-immobilized bimetallic Pt/Ir alloyed nanoclusters (NCs) and
      4-tert-butylcatechol, for the aerobic oxidation of amines to imines under ambient
      conditions. After optimization, the desired imines were obtained in good to
      excellent yields with broad substrate scope. The reaction rate was determined to
      be first-order with respect to the substrate and catechol and zero-order for the
      alloyed Pt/Ir NC catalyst. Control studies revealed that both the heterogeneous
      NC catalyst and 4-tert-butylcatechol are essential and act cooperatively to
      facilitate the aerobic oxidation under mild conditions.

PMID- 22852769
TI  - Hierarchical clustering of gene expression patterns in the Eomes + lineage of
      excitatory neurons during early neocortical development.
AB  - BACKGROUND: Cortical neurons display dynamic patterns of gene expression during
      the coincident processes of differentiation and migration through the developing
      cerebrum. To identify genes selectively expressed by the Eomes + (Tbr2) lineage
      of excitatory cortical neurons, GFP-expressing cells from Tg(Eomes::eGFP) Gsat
      embryos were isolated to > 99% purity and profiled. RESULTS: We report the
      identification, validation and spatial grouping of genes selectively expressed
      within the Eomes + cortical excitatory neuron lineage during early cortical
      development. In these neurons 475 genes were expressed >= 3-fold, and 534 genes
      <= 3-fold, compared to the reference population of neuronal precursors. Of the up
      regulated genes, 328 were represented at the Genepaint in situ hybridization
      database and 317 (97%) were validated as having spatial expression patterns
      consistent with the lineage of differentiating excitatory neurons. A novel
      approach for quantifying in situ hybridization patterns (QISP) across the
      cerebral wall was developed that allowed the hierarchical clustering of genes
      into putative co-regulated groups. Forty four candidate genes were identified
      that show spatial expression with Intermediate Precursor Cells, 49 candidate
      genes show spatial expression with Multipolar Neurons, while the remaining 224
      genes achieved peak expression in the developing cortical plate. CONCLUSIONS:
      This analysis of differentiating excitatory neurons revealed the expression
      patterns of 37 transcription factors, many chemotropic signaling molecules
      (including the Semaphorin, Netrin and Slit signaling pathways), and unexpected
      evidence for non-canonical neurotransmitter signaling and changes in mechanisms
      of glucose metabolism. Over half of the 317 identified genes are associated with
      neuronal disease making these findings a valuable resource for studies of
      neurological development and disease.

PMID- 22852771
TI  - Evidence of preorganization in quinonoid intermediate formation from L-Trp in
      H463F mutant Escherichia coli tryptophan indole-lyase from effects of pressure
      and pH.
AB  - The effects of pH and hydrostatic pressure on the reaction of H463F tryptophan
      indole-lyase (TIL) have been evaluated. The mutant TIL shows very low activity
      for elimination of indole but is still competent to form a quinonoid intermediate
      from l-tryptophan [Phillips, R. S., Johnson, N., and Kamath, A. V. (2002)
      Biochemistry 41, 4012-4019]. Stopped-flow measurements show that the formation of
      the quinonoid intermediate at 505 nm is affected by pH, with a bell-shaped
      dependence for the forward rate constant, k(f), and dependence on a single basic
      group for the reverse rate constant, k(r), with the following values: pK(a1) =
      8.14 +/- 0.15, pK(a2) = 7.54 +/- 0.15, k(f,min) = 18.1 +/- 1.3 s(-1), k(f,max) =
      179 +/- 46.3 s(-1), k(r,min) = 11.4 +/- 1.2 s(-1), and k(r,max) = 33 +/- 1.6 s(
      1). The pH effects may be due to ionization of Tyr74 as the base and Cys298 as
      the acid influencing the rate constant for deprotonation. High-pressure stopped
      flow measurements were performed at pH 8, which is the optimum for the forward
      reaction. The rate constants show an increase with pressure up to 100 MPa and a
      subsequent decrease above 100 MPa. Fitting the pressure data gives the following
      values: k(f,0) = 15.4 +/- 0.8 s(-1), DeltaV(?) = -29.4 +/- 2.9 cm(3) mol(-1), and
      Deltabeta(?) = -0.23 +/- 0.03 cm(3) mol(-1) MPa(-1) for the forward reaction, and
      k(r,0) = 20.7 +/- 0.8 s(-1), DeltaV(?) = -9.6 +/- 2.3 cm(3) mol(-1), and
      Deltabeta(?) = -0.05 +/- 0.02 cm(3) mol(-1) MPa(-1) for the reverse reaction. The
      primary kinetic isotope effect on quinonoid intermediate formation at pH 8 is
      small (~2) and is not significantly pressure-dependent, suggesting that the
      effect of pressure on k(f) may be due to perturbation of an active site
      preorganization step. The negative activation volume is also consistent with
      preorganization of the ES complex prior to quinonoid intermediate formation, and
      the negative compressibility may be due to the effect of pressure on the enzyme
      conformation. These results support the conclusion that the preorganization of
      the H463F TIL Trp complex, which is probably dominated by motion of the l-Trp
      indole moiety of the aldimine complex, contributes to quinonoid intermediate
      formation.

PMID- 22852770
TI  - Colorectal cancer mortality and industrial pollution in Spain.
AB  - BACKGROUND: Records kept as a result of the implementation of Integrated
      Pollution Prevention and Control (IPPC) and the European Pollutant Release and
      Transfer Register (E-PRTR) constitute a public inventory of industries, created
      by the European Commission, which is a valuable resource for monitoring
      industrial pollution. Our objective is to ascertain whether there might be excess
      colorectal cancer mortality among populations residing in the vicinity of Spanish
      industrial installations that are governed by the IPPC Directive and E-PRTR
      Regulation and report their emissions to air. METHODS: An ecological study was
      designed to examine colorectal cancer mortality at a municipal level (8098
      Spanish towns), over the period 1997-2006. We conducted an exploratory "near vs.
      far" analysis to estimate the relative risks (RR) of towns situated at a distance
      of less than 2 km from industrial installations. The analysis was repeated for
      each of the 24 industrial groups. RR and their 95% credible/confidence intervals
      (95%CI) were estimated on the basis of Poisson regression models, using two types
      of modelling: a) the conditional autoregressive Bayesian model proposed by Besag,
      York and Mollie, with explanatory variables; and b) a mixed regression model.
      Integrated nested Laplace approximations were used as a Bayesian inference tool.
      RESULTS: Statistically significant RRs were detected in the vicinity of mining
      industry (RR 1.258; 95%CI 1.082 - 1.463), paper and wood production (RR 1.071;
      95%CI 1.007 - 1.140), food and beverage sector (RR 1.069; 95%CI 1.029 - 1.111),
      metal production and processing installations (RR 1.065; 95% CI 1.011 - 1.123)
      and ceramics (RR 1.050 ; 95%CI 1.004 - 1.099). CONCLUSIONS: Given the exploratory
      nature of this study, it would seem advisable to check in other countries or with
      other designs, if the proximity of industries that emit pollutants into the air
      could be an added risk factor for colorectal cancer mortality. Nevertheless, some
      of the differences between men and women observed in the analyses of the
      industrial groups suggest that there may be a component of occupational exposure,
      little-studied in the case of cancers of the digestive system.

PMID- 22852774
TI  - Resiliance and health. Abstracts of the 26th Conference of the European Health
      Psychology Society. Prague, Czech Republic. August 21-25, 2012.

PMID- 22852773
TI  - Inflammation and prostate carcinogenesis.
AB  - Quite a few epidemiological studies including meta-analyses indicate that
      prostate inflammation is associated with increased risk of prostate cancer. The
      cause of inflammation in the prostate is speculated to be several microorganisms
      that cause prostatitis or sexually transmitted infections. Other specific
      microorganisms, such as xenotropic murine leukemia virus-related virus, are also
      reported to relate to the development of prostate cancer; however, the
      contribution of this microorganism to prostate cancer development needs to be
      carefully interpreted. Environmental factors, especially dietary factors, might
      also be associated with prostate cancer development. Among related dietary
      factors, charred meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      might be a link between environmental factors and inflammation, because 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine has the potential to accelerate prostate
      inflammation through its estrogenic effect. In light of these findings,
      preventing or reducing prostate inflammation might be one strategy for
      chemoprevention of prostate cancer.

PMID- 22852775
TI  - Release behaviour of carbamazepine-loaded poly(epsilon
      caprolactone)/poly(ethylene oxide) microspheres.
AB  - Poly(epsilon-caprolactone) (PCL), a biodegradable and biocompatible aliphatic
      polyester has a great potential as a drug carrying material in controlled drug
      delivery/release systems. The most simple and economical way to tailor the
      release profile of active substances from biodegradable polymer matrix is by the
      addition of the second polymeric component in the polymer matrix, i.e. by
      blending. This study describes the preparation and characterization of a
      carbamazepine-loaded microspheres by the use of PCL blended with poly(ethylene
      oxide) as a drug carrying material. By the use of two-component
      hydrophilic/hydrophobic polymer blend as a microspheres' matrix material, release
      profile of the drug can be modified and dictated. The microspheres prepared by
      classical oil-in-water emulsion solvent evaporation technique were characterized
      with respect to particle size and morphology, polymer matrix composition,
      encapsulation efficiency, physical state of the drug and in vitro release
      behaviour. It was presented that the release profile can be modified by the
      presence and the amount of hydrophilic component in the starting formulation of
      microspheres.

PMID- 22852776
TI  - Assessment of hygiene standards and Hazard Analysis Critical Control Points
      implementation on passenger ships.
AB  - The level of hygiene on ferries can have impact on travellers' health. The aim of
      this study was to assess the hygiene standards of ferries in Greece and to
      investigate whether Hazard Analysis Critical Control Points (HACCP)
      implementation contributes to the hygiene status and particularly food safety
      aboard passenger ships. Hygiene inspections on 17 ferries in Greece were
      performed using a standardized inspection form, with a 135-point scale. Thirty
      four water and 17 food samples were collected and analysed. About 65% (11/17) of
      ferries were scored with >100 points. Ferries with HACCP received higher scores
      during inspection compared to those without HACCP (p value <0.001). All 34
      microbiological water test results were found negative and, from the 17 food
      samples, only one was found positive for Salmonella spp. Implementation of
      management systems including HACCP principles can help to raise the level of
      hygiene aboard passenger ships.

PMID- 22852777
TI  - Pd-catalyzed benzylic C-H amidation with benzyl alcohols in water: a strategy to
      construct quinazolinones.
AB  - A novel method for the synthesis of 4-phenylquinazolinones via a palladium
      catalyzed domino reaction of o-aminobenzamides with benzyl alcohols is developed.
      This protocol involves N-benzylation, benzylic C-H amidation, and dehydrogenation
      in water, which may play an important role in the smooth generation of the
      (eta(3)-benzyl)palladium species by activation of the hydroxyl group of the
      benzyl alcohol.

PMID- 22852779
TI  - Polyfunctional ionogenic compound sorption: challenges and new approaches to
      advance predictive models.
AB  - Polyfunctional ionogenic compounds are unique in that they sorb to environmental
      solids at multiple receptor sites via multiple interaction mechanisms. However,
      existing sorption models fail to accommodate: (i) sorption via a single mechanism
      (e.g., cation exchange) at one sorbent receptor site type (e.g., exchange site)
      distributed across multiple soil components (e.g., organic matter and
      aluminosilicates); and (ii) sorption at a specific sorbent receptor site (e.g.,
      exchange site) involving distinct sorbate structural moieties (e.g., -NH(3)(+)
      and -COOH) and distinct interaction mechanisms (e.g., cation exchange and cation
      bridging). In response, this study offers a mechanism-based framework for
      conceptualizing the equilibrium solid-water sorption coefficient, K(d), with
      particular emphasis on the mechanisms of cation exchange and surface
      complexation/cation bridging. The unique mapping of sorbate structural moieties,
      sorbent receptor sites, and sorption mechanisms is used to advance mechanism
      specific probe compounds for cation exchange and surface complexation/cation
      bridging for quantifying the relevant site abundance and baseline sorption free
      energy. Existing literature studies point to the feasibility of developing
      mechanism-specific structural corrections to "adjust" mechanism-specific probe
      sorption measures to estimate the magnitude of sorption for any polyfunctional
      ionogenic compound of interest. Advancement of our conceptual framework to a
      quantitative K(d) model requires more extensive evaluation of ionogenic compound
      sorption under consistent experimental conditions.

PMID- 22852778
TI  - Tumor response and survival in patients with advanced non-small-cell lung cancer:
      the predictive value of chemotherapy-induced changes in fibrinogen.
AB  - BACKGROUND: Hyperfibrinogenemia is a common problem associated with various
      carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell
      lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced
      changes in fibrinogen level relate to chemotherapeutic response and prognosis.
      The purposes of this study were to: 1) analyze the association between
      chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic
      response after the first two courses of standard first-line platinum-based
      chemotherapy; and 2) evaluate the prognostic significance of the basal plasma
      fibrinogen level in patients with advanced NSCLC. METHODS: In this retrospective
      study, the data from 160 patients with advanced NSCLC were collected. The
      association between the changes in fibrinogen and the response to chemotherapy,
      or between the pre-and post-chemotherapy fibrinogen levels and patient clinical
      characteristics, were analyzed using SPSS software. In addition, the prognostic
      value of pre-chemotherapy fibrinogen levels was assessed. RESULTS: The median pre
      chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma
      fibrinogen levels correlated significantly with gender (p = 0.041). Post
      chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p
      = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen
      levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre
      chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a
      significant link between the decrease in fibrinogen level, and initial partial
      response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and
      multivariate analysis revealed that higher levels of fibrinogen (>=4.4 g/L) and
      ECOG 1 were positively associated with shorter overall survival (OS). CEA and
      CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after
      chemotherapy. CONCLUSIONS: This study showed that the reduction in plasma
      fibrinogen levels induced by chemotherapy might be as a promising biomarker as
      CEA and CA125 for evaluating the efficacy of chemotherapy in advanced NSCLC. In
      addition, basal plasma fibrinogen levels could be used as an independent
      prognostic parameter for the OS of patients with advanced NSCLC.

PMID- 22852780
TI  - Developing behavioural training services to meet defined standards within an
      Australian statewide disability service system and the associated client
      outcomes.
AB  - BACKGROUND: LaVigna, Christian, and Willis (2005) reported on a project where
      Institute for Applied Behaviour Analysis (IABA) staff trained a professional team
      in New Zealand (NZ) to provide behavioural services that met defined criteria.
      The NZ team was then trained to train other practitioners to meet the same
      professional standards. However, no client outcomes were reported in that study.
      METHOD: This study replicates the NZ study within disability services in
      Tasmania, Australia. Further, this study examined the associated client outcomes
      and the impact of the training on severity ratings of subsequent referrals.
      RESULTS: Tasmanian trainers trained participants to provide behavioural services
      that met the same professional standards. Client behavioural outcome data showed
      significant improvement. Referral data showed decreases in severity ratings.
      CONCLUSIONS: The trainer of trainers process is effective in training staff to
      meet defined professional standards, including desired client outcomes, and to
      effectively make positive behaviour support accessible to a large number of
      people.

PMID- 22852781
TI  - Active and passive problem solving as moderators of the relation between negative
      life event stress and suicidal ideation among suicide attempters and non
      attempters.
AB  - This study examined whether active problem solving would buffer against, whereas
      passive problem solving would exacerbate, the association of negative life stress
      with suicidal ideation. Young adult college students (73 females, M(age) = 19.0)
      from a diverse urban public university, with (n = 37) and without (n = 59) a
      suicide attempt history completed measures of life stress, problem solving,
      hopelessness, depression, and suicidal ideation. Hierarchical linear regressions
      were conducted to test moderating roles of active and passive problem solving,
      along with suicide attempt history, on the relation between negative life event
      stress and suicidal ideation. There was a weaker relation between life stress and
      suicidal ideation at high and average levels of relevant problem solving than at
      low levels, and this was the case primarily for suicide attempters but not for
      non-attempters. Individuals with a past attempt produced more passive solutions
      than non-attempters, but among attempters, even passive problem solving buffered
      the association of life stress with suicidal ideation. Relevant problem solving
      in the face of life stress may be especially important for individuals vulnerable
      to suicidal ideation due to an attempt history. Among such at-risk individuals,
      generating even passive solutions in the face of life stress may be more adaptive
      than generating few solutions. Thus, clinical interventions with suicide
      attempters that focus on generating solutions to problems, even if these are
      initially passive, may help mitigate the effect of life stress on suicidal
      ideation.

PMID- 22852783
TI  - The roles of affect dysregulation and positive affect in non-suicidal self
      injury.
AB  - Non-suicidal self-injury (NSSI) is a prevalent behavior, yet little is known
      about associated affective mechanisms. Research has focused on the role of
      negative affect in NSSI, with positive affect receiving relatively less
      attention. This study examined affect dysregulation, emotional reactivity, and
      the experience of positive and negative affect in NSSI. Path analyses revealed
      that emotional reactivity predicted positive and negative affect after NSSI.
      Positive affect, in turn, predicted more lifetime acts of NSSI. The results
      demonstrate the importance of examining multiple facets of affect regulation, as
      well as the roles of both negative and positive affect in NSSI.

PMID- 22852782
TI  - The moderating role of distress tolerance in the relationship between
      posttraumatic stress disorder symptom clusters and suicidal behavior among trauma
      exposed substance users in residential treatment.
AB  - The co-occurrence of posttraumatic stress disorder (PTSD) and substance use
      disorders (SUDs) is associated with greater risk for suicidal behavior than
      either disorder alone. Research highlights the relevance of PTSD symptoms in
      particular to suicide risk within this population. Research has also provided
      support for an association between distress tolerance (DT) and both PTSD symptoms
      and suicidal behavior. This study examined the role of DT in the relationship
      between PTSD symptom severity and suicidal behavior in a sample of 164 SUD
      inpatients with a history of Criterion A traumatic exposure. Results indicated
      that DT moderated the relationship between PTSD symptoms (overall, re
      experiencing, and hyperarousal) and medically attended suicide attempts, with the
      magnitude of the relationship increasing at higher levels of DT.

PMID- 22852784
TI  - Investigating dimensionality of Eskin's attitudes toward suicide scale with
      Mokken scaling and confirmatory factor analysis.
AB  - Attitudes toward suicide are often investigated by means of questionnaires, most
      of which are overly long or of low psychometric quality. Eskin's ( 2004 )
      Attitudes Towards Suicide Scale is short and first investigations suggest good
      psychometric properties, but its factor structure has scarcely been explored.
      Hence, we examined this instrument by a data-analytic approach that combines
      Mokken scaling and confirmatory factor analysis (CFA). Results revealed 6
      factors, of which 1 possessed only weak measurement properties. CFAs indicated
      only borderline fit of models found in prior research, but adequate fit for the
      scale structures revealed by Mokken scaling. Psychometric properties of these
      scales were satisfactory. Both the instrument as well as the methodological
      approach presented here can be recommended for further research.

PMID- 22852785
TI  - Globalization and suicide: an ecological study across five regions of the world.
AB  - The impact of globalization on health is recognized to be influenced by country
      and regional-level factors. This study aimed to investigate the possible
      relationship between globalization and suicide in five world regions. An index
      measure of globalization was developed at the country level over 1980 to 2006.
      The association between the index and sex specific suicide rates was tested using
      a fixed-effect regression model. Over time, the globalization index seemed to be
      associated with increased suicide rates in Asia and the Eastern European/Baltic
      region. In contrast, it was associated with decreased rates in Scandinavia. There
      was no significant relationship between globalization and suicide in Southern and
      Western Europe. The effects of globalization could be determined by specific
      regional (i.e., cultural and societal) factors. Identification of these mediators
      might provide opportunities to protect countries from the adverse impacts of
      globalization.

PMID- 22852786
TI  - Qualitative evaluation of suicide and overdose risk assessment procedures among
      veterans in substance use disorder treatment clinics.
AB  - The objective of this study was to examine risk assessment practices for suicide
      and unintentional overdose to inform ongoing care in substance use disorder
      clinics. Focus groups were conducted via telephone among a random sample of
      treatment providers (N = 19) from Veterans Health Administration substance use
      disorder clinics across the nation. Themes were coded by research staff.
      Treatment providers reported consistent and clear guidelines for risk assessment
      of suicide among patients. Unintentional overdose questions elicited dissimilar
      responses which indicated a lack of cohesion and uniformity in risk assessment
      practices across clinics. Suicide risk assessment protocols are cohesively
      implemented by treatment providers. Unintentional overdose risk, however, may be
      less consistently assessed in clinics.

PMID- 22852787
TI  - Seeking validation in unlikely places: the nature of online questions about non
      suicidal self-injury.
AB  - Recent research points to the salience of the Internet as a means to seek
      information about non-suicidal self-injury (NSSI) but no research has explored
      what is asked about NSSI online. The current study examined the nature of NSSI
      questions asked on Yahoo! Answers. One hundred and eight questions were analyzed
      using a content analysis. The most frequently asked questions pertained to
      seeking validation for NSSI experiences (30.56%); however, the responses provided
      were sometimes quite invalidating. Other common questions included those related
      to general NSSI information (17.59%), scar concealment (11.11%), and NSSI-related
      media (11.11%). Efforts are needed to provide NSSI resources and support online
      but websites may need to be monitored to safeguard against unhelpful responses.

PMID- 22852788
TI  - Proteomic analysis of differences in ectoderm and mesoderm membranes by DiGE.
AB  - Ectoderm and mesoderm can be considered as prototypes for epithelial and
      mesenchymal cell types. These two embryonic tissues display clear differences in
      adhesive and motility properties, which are phenomenologically well characterized
      but remain largely unexplored at the molecular level. Because the key downstream
      regulations must occur at the plasma membrane and in the underlying actin
      cortical structures, we have set out to compare the protein content of membrane
      fractions from Xenopus ectoderm and mesoderm tissues using 2-dimensional
      difference gel electrophoresis (DiGE). We have thus identified several proteins
      that are enriched in one or the other tissues, including regulators of the
      cytoskeleton and of cell signaling. This study represents to our knowledge the
      first attempt to use proteomics specifically targeted to the membrane-cortex
      compartment of embryonic tissues. The identified components should help
      unraveling a variety of tissue-specific functions in the embryo.

PMID- 22852789
TI  - Development of a perfusion chamber assay to study in real time the kinetics of
      thrombosis and the antithrombotic characteristics of antiplatelet drugs.
AB  - BACKGROUND: Arterial thrombosis triggered by vascular injury is a balance
      between thrombus growth and thrombus fragmentation (dethrombosis). Unbalance
      towards thrombus growth can lead to vascular occlusion, downstream ischemia and
      tissue damage.Here we describe the development of a simple methodology that
      allows for continuous real time monitoring and quantification of both processes
      during perfusion of human blood under arterial shear rate conditions. Using this
      methodology, we have studied the effects of antiplatelet agents targeting COX-1
      (aspirin), P2Y12 (2-MeSAMP, clopidogrel), GP IIb-IIIa (eptifibatide) and their
      combinations on the kinetics of thrombosis over time. RESULTS: Untreated samples
      of blood perfused over type III collagen at arterial rates of shear promoted the
      growth of stable thrombi. Modulation by eptifibatide affected thrombus growth,
      while that mediated by 2-MeSAMP and aspirin affected thrombus stability. Using
      this technique, we confirmed the primacy of continuous signaling by the ADP
      autocrine loop acting on P2Y12 in the maintenance of thrombus stability. Analysis
      of the kinetics of thrombosis revealed that continuous and prolonged analysis of
      thrombosis is required to capture the role of platelet signaling pathways in
      their entirety. Furthermore, studies evaluating the thrombotic profiles of 20
      healthy volunteers treated with aspirin, clopidogrel or their combination
      indicated that while three individuals did not benefits from either aspirin or
      clopidogrel treatments, all individuals displayed marked destabilization profiles
      when treated with the combination regimen. CONCLUSIONS: These results show the
      utility of a simple perfusion chamber technology to assess in real time the
      activity of antiplatelet drugs and their combinations. It offers the opportunity
      to perform pharmacodynamic monitoring of arterial thrombosis in clinical trials
      and to investigate novel strategies directed at inhibiting thrombus stability in
      the management of cardiovascular disease.

PMID- 22852790
TI  - The PRIPS study: screening battery for subjects at risk for Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Screening batteries to narrow down a target-at-risk
      population are essential for trials testing neuroprotective compounds aiming to
      delay or prevent onset of Parkinson's disease (PD). METHODS: The PRIPS study
      focuses on early detection of incident PD in 1847 at baseline PD-free subjects,
      and assessed age, male gender, positive family history, hyposmia, subtle motor
      impairment and enlarged substantia nigra hyperechogenicity (SN+). RESULTS: After
      3 years follow-up 11 subjects had developed PD. In this analysis of the secondary
      outcome parameters, sensitivity and specificity of baseline markers for incident
      PD were calculated in 1352 subjects with complete datasets (10 PD patients). The
      best approach for prediction of incident PD comprised three steps: (i)
      prescreening for age, (ii) primary screening for positive family history and/or
      hyposmia, and (iii) secondary screening for SN+. CONCLUSION: With this approach,
      one out of 16 positively screened participants developed PD compared to one out
      of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a
      specificity of 90.6% and a positive predictive value of 6.1%. These values are
      higher than for any single screening instrument but still too low for a feasible
      and cost-effective screening strategy which might require longer follow-up
      intervals and application of additional instruments.

PMID- 22852791
TI  - Langmuir monolayers of an inclusion complex formed by a new calixarene derivative
      and fullerene.
AB  - The design of new molecules with directed interactions to functional molecules as
      complementary building blocks is one of the main goals of supramolecular
      chemistry. A new p-tert-butylcalix[6]arene monosubstituted derivative bearing
      only one alkyl chain with an acid group (C6A3C) has been synthesized. The C6A3C
      has been successfully used for building Langmuir monolayers at the air-water
      interface. The C6A3C molecule adopts a flatlike orientation with respect to the
      air-water interface. The molecular structure gives the molecule amphiphilic
      character, while allowing the control of both the dissociation degree and the
      molecular conformation at the air-water interface. The C63AC has been combined
      with pristine fullerene (C60) to form the supramolecular complex C6A3C:C60 in 2:1
      molar ratio (CFC). The CFC complex retains the ability of C6A3C to form Langmuir
      monolayers at the air/water interface. The interfacial molecular arrangement of
      the CFC complex has been convincingly described by in situ UV-vis reflection
      spectroscopy and synchrotron X-ray reflectivity measurements. Computer
      simulations complement the experimental data, confirming a perpendicular
      orientation of the calixarene units of CFC with respect to the air-water
      interface. This orientation is stabilized by the formation of intermolecular H
      bonds. The interfacial monolayer of the CFC supramolecular complex is proposed as
      a useful model for the well-defined self-assembly of recognition and functional
      building blocks.

PMID- 22852792
TI  - Integrating a pharmacist into the general practice environment: opinions of
      pharmacist's, general practitioner's, health care consumer's, and practice
      manager's.
AB  - BACKGROUND: Pharmacists are viewed as highly trained yet underutilised and there
      is growing support to extend the role of the pharmacist within the primary health
      care sector. The integration of a pharmacist into a general practice medical
      centre is not a new concept however is a novel approach in Australia and evidence
      supporting this role is currently limited. This study aimed to describe the
      opinions of local stakeholders in South-East Queensland on the integration of a
      pharmacist into the Australian general practice environment. METHODS: A sample of
      general practitioners, health care consumers, pharmacists and practice managers
      in South-East Queensland were invited to participate in focus groups or semi
      structured interviews. Seeding questions common to all sessions were used to
      facilitate discussion. Sessions were audio recorded and transcribed verbatim.
      Leximancer software was used to qualitatively analyse responses. RESULTS: A total
      of 58 participants took part in five focus groups and eighteen semi-structured
      interviews. Concepts relating to six themes based on the seeding questions were
      identified. These included positively viewed roles such as medication reviews and
      prescribing, negatively viewed roles such as dispensing and diagnosing, barriers
      to pharmacist integration such as medical culture and remuneration, facilitators
      to pharmacist integration such as remuneration and training, benefits of
      integration such as access to the patient's medical file, and potential funding
      models. CONCLUSIONS: These findings and future research may aid the development
      of a new model of integrated primary health care services involving pharmacist
      practitioners.

PMID- 22852794
TI  - Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of
      fungus farming during periods of global warming.
AB  - BACKGROUND: Fungus farming is an unusual life style in insects that has evolved
      many times in the wood boring weevils named 'ambrosia beetles'. Multiple
      occurrences of this behaviour allow for a detailed comparison of the different
      origins of fungus farming through time, its directionality, and possible
      ancestral states. We tested these hypotheses with a phylogeny representing the
      largest data set to date, nearly 4 kb of nucleotides from COI, EF-1alpha, CAD,
      ArgK, 28S, and 200 scolytine taxa. RESULTS: Phylogenetic analyses using Bayesian
      or parsimony approaches placed the root of Scolytinae close to the tribe
      Scolytini and Microborus, but otherwise indicated low resolution at older nodes.
      More recent clades were well resolved, including ten origins of fungus farming.
      There were no subsequent reversals to bark or phloem feeding in the fungus
      farming clades. The oldest origin of fungus farming was estimated near 50 Ma,
      long after the origin of Scolytinae (100-120 Ma). Younger origins included the
      species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of
      independence between traits indicated that neither gregarious larval feeding nor
      regular inbreeding by sibling mating was strongly correlated with the origin of
      fungus farming. CONCLUSION: Origins of fungus farming corresponded mainly with
      two periods of global warming in the Cenozoic era, which were characterised by
      broadly distributed tropical forests. Hence, it seems likely that warm climates
      and expanding tropical angiosperm forests played critical roles in the successful
      radiation of diverse fungus farming groups. However, further investigation will
      likely reveal additional biological factors that promote fungus farming.

PMID- 22852795
TI  - Outcome of venom bradykinin potentiating factor on rennin-angiotensin system in
      irradiated rats.
AB  - PURPOSE: The objective of this work was to compare the effect of a bradykinin
      potentiating (BPF) isolated from venom of Egyptian scorpion Androctonus amoreuxi
      as a natural angiotensin converting enzyme inhibitor (ACEI) with losartan (LOS),
      a chemical angiotensin receptor blocker (ARB), in the modulation of radiation
      induced damage. MATERIAL AND METHODS: Rats were grouped into: (i) CONTROL:
      untreated; (ii) + C(BPF): Received intraperitoneally (i.p.) BPF 1 MUg/g body
      weight (b.w.) (twice/week) during 3 weeks; (iii) + C(LOS:) Received i.p. LOS 5
      MUg/g b.w. (twice/week) during 3 weeks; (iv) R: Irradiated at 4 Gy; (v) R + BPF
      and (vi) R + LOS: Received BPF or LOS post-irradiation for 3 weeks. RESULTS: BPF
      or LOS treatment induced a significant drop of sodium and uric acid. Irradiation
      induced a significant elevation of malondialdehyde (MDA) and advanced oxidation
      protein product (AOPP) associated with a significant decrease of glutathione
      (GSH) content in the kidney. Serum aldosterone, sodium, urea and creatinine
      levels showed a significant increase while a significant drop was recorded for
      haematological values, calcium and uric acid levels. Treatment of irradiated
      animals with BPF or LOS significantly improved radiation-induced changes.
      CONCLUSION: It could be concluded that the use of BPF as a natural product is
      comparable to the chemical compound LOS.

PMID- 22852796
TI  - Detection of multiple drug-resistant Trypanosoma congolense populations in
      village cattle of south-east Mali.
AB  - BACKGROUND: Tsetse fly-transmitted African animal trypanosomosis causes annual
      losses that run into billions of dollars. The disease is assumed to cause hunger
      and poverty in most sub-Saharan countries since it represents a serious
      impediment to sustainable livestock production. Both a cross-sectional and a
      longitudinal study were carried out from November to December 2007 to evaluate
      trypanosomosis risk and susceptibility of trypanosomes to trypanocidal drug
      treatment in village cattle populations in south-east Mali. METHODS: Eight
      purposively selected villages participated in the study. In each village, eight
      traps deployed along drainage lines over 24 hour duration were used to catch
      tsetse. One hundred systematically selected cattle in the study villages were
      examined for trypanosomes. All trypanosome-positive cattle were randomly
      allocated into two treatment groups: a group treated with 0.5 mg/kg bw.
      isometamidium chloride (ISMM) and a group treated with 3.5 mg/kg bw. diminazene
      aceturate (DIM). The cattle were monitored for trypanosomes at day 14 and 28 post
      treatment. RESULTS: Of the 796 cattle examined, 125 (15.7%) were trypanosome
      positive. Village trypanosome prevalences ranged between 11% and 19%. There were
      no significant (p > 0.05) differences in the village trypanosome prevalences.
      Trypanosoma congolense was the dominant trypanosome species accounting for 73%
      (91/125) of the infections and T. vivax the remainder. Twenty (31.7%) of the 63
      cattle on 0.5 mg/kg bw. ISMM treatment were still positive14 days post-treatment.
      Of the 43 aparasitaemic cattle monitored to day 28, 25.6% (11) became
      parasitaemic, resulting in a cumulative failure rate of 49.2% (31/63).
      Trypanosoma congolense accounted for 77.4% (24/31) of failed ISMM treatments. The
      62 cattle treated with 3.5 mg/kg bw. DIM resulted in 30.6% (19/62) failed
      treatments. Although 42.2% (19/45) of T. congolense positive cattle did not
      respond to DIM treatment, all T. vivax positive cattle responded positively to
      DIM treatment. CONCLUSIONS: The overreliance on trypanocides in the control of
      trypanosomosis will ultimately lead to multiple drug-resistant trypanosome
      populations as detected in villages in south-east Mali rendering the use of drugs
      doubtful. Effective alternative methods for trypanosomosis control ought to
      substitute chemotherapy to ensure sustainable cattle production in these
      villages. Since there is no single strategy for containing trypanocidal drug
      resistance, promotion of an integrated approach combining proven trypanosomosis
      control approaches in high trypanosomosis risk areas is most desirous. The best
      bet strategy this study recommended for areas with multiple drug resistance
      included area-wide community tsetse control, control of co-infections to exploit
      self-cure against resistant trypanosome populations and the rational use of
      trypanocidal drugs which should be urgently promoted at all levels as a way of
      containing or reversing resistance.

PMID- 22852797
TI  - The role of the maximum involvement of biopsy core in predicting outcome for
      patients treated with dose-escalated radiation therapy for prostate cancer.
AB  - PURPOSE: To evaluate the influence of the maximum involvement of biopsy core
      (MIBC) on outcome for prostate cancer patients treated with dose-escalated
      external beam radiotherapy (EBRT). METHODS AND MATERIALS: The outcomes of 590 men
      with localized prostate cancer treated with EBRT (>=75 Gy) at a single
      institution were retrospectively analyzed. The influence of MIBC on freedom from
      biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific
      survival (CSS), and overall survival (OS) was compared to other surrogates for
      biopsy tumor volume, including the percentage of positive biopsy cores (PPC) and
      the total percentage of cancer volume (PCV). RESULTS: MIBC correlated with PSA, T
      stage, Gleason score, NCCN risk group, PPC, PCV, and treatment related factors.
      On univariate analysis, MIBC was prognostic for all endpoints except OS; with
      greatest impact in those with Gleason scores of 8-10. However, on multivariate
      analysis, MIBC was only prognostic for FFBF (hazard ratio [HR] 1.9, p = 0.008),
      but not for FFM (p = 0.19), CSS (p = 0.16), and OS (p = 0.99). CONCLUSIONS: In
      patients undergoing dose-escalated EBRT, MIBC had the greatest influence in those
      with Gleason scores of 8-10 but provided no additional prognostic data as
      compared to PPC and PCV, which remain the preferable prognostic variables in this
      patient population.

PMID- 22852798
TI  - White versus gray matter: fMRI hemodynamic responses show similar
      characteristics, but differ in peak amplitude.
AB  - BACKGROUND: There is growing evidence for the idea of fMRI activation in white
      matter. In the current study, we compared hemodynamic response functions (HRF) in
      white matter and gray matter using 4 T fMRI. White matter fMRI activation was
      elicited in the isthmus of the corpus callosum at both the group and individual
      levels (using an established interhemispheric transfer task). Callosal HRFs were
      compared to HRFs from cingulate and parietal activation. RESULTS: Examination of
      the raw HRF revealed similar overall response characteristics. Finite impulse
      response modeling confirmed that the WM HRF characteristics were comparable to
      those of the GM HRF, but had significantly decreased peak response amplitudes.
      CONCLUSIONS: Overall, the results matched a priori expectations of smaller HRF
      responses in white matter due to the relative drop in cerebral blood flow (CBF)
      and cerebral blood volume (CBV). Importantly, the findings demonstrate that
      despite lower CBF and CBV, white matter fMRI activation remained within
      detectable ranges at 4 T.

PMID- 22852800
TI  - Organocatalytic one-pot asymmetric synthesis of 4H,5H-pyrano[2,3-c]pyrazoles.
AB  - An efficient one pot asymmetric synthesis of tetrahydropyrano[2,3-c]pyrazoles has
      been developed. This class of biologically active heterocycles can be obtained
      via a secondary amine catalyzed asymmetric Michael/Wittig/oxa-Michael reaction
      sequence. Remarkably, the title compounds were accessible in good to very good
      yields and very good to excellent enantioselectivities after a single
      purification step.

PMID- 22852799
TI  - The Healthy Start project: a randomized, controlled intervention to prevent
      overweight among normal weight, preschool children at high risk of future
      overweight.
AB  - BACKGROUND: Research shows that obesity prevention has to start early. Targeting
      interventions towards subgroups of individuals who are predisposed, but yet
      normal weight, may prove more effective in preventing overweight than
      interventions towards unselected normal weight subsets. Finally, interventions
      focused on other factors than diet and activity are lacking. The objectives were
      to perform a randomized, controlled intervention aiming at preventing overweight
      in children aged 2-6 years, who are yet normal weight, but have high
      predisposition for future overweight, and to intervene not only by improving diet
      and physical activity, but also reduce stress and improve sleep quality and
      quantity. METHODS/DESIGN: Based on information from the Danish National Birth
      Registry and administrative birth forms, children were selected based on having
      either a high birth weight, a mother who was overweight prior to pregnancy, or a
      familial low socioeconomic status. Selected children (n = 5,902) were randomized
      into three groups; an intervention group, a shadow control group followed in
      registers exclusively, and a control group examined at the beginning and at the
      end of the intervention. Approximately 21% agreed to participate. Children who
      presented as overweight prior to the intervention were excluded from this study
      (n = 92). In the intervention group, 271 children were included, and in the
      control group 272 were included. Information obtained from the shadow control
      group is on-going, but it is estimated that 394 children will be included. The
      intervention took place over on average 11/2 year between 2009 and 2011, and
      consisted of optional individual guidance in optimizing diet and physical
      activity habits, reducing chronic stress and stressful events and improving sleep
      quality and quantity. The intervention also included participation in cooking
      classes and play arrangements. Information on dietary intake, meal habits,
      physical activity, sleep habits, and overall stress level was obtained by 4-7 day
      questionnaire diaries and objective measurements. DISCUSSION: If the Healthy
      Start project is effective in preventing excessive weight gain, it will provide
      valuable information on new determinants of obesity which should be considered in
      future interventions, and on new strategies to prevent development of overweight
      and obesity at an early age.

PMID- 22852801
TI  - A new air quality perception scale for global assessment of air pollution health
      effects.
AB  - Despite improvements in air quality in developed countries, air pollution remains
      a major public health issue. To fully assess the health impact, we must consider
      that air pollution exposure has both physical and psychological effects; this
      latter dimension, less documented, is more difficult to measure and subjective
      indicators constitute an appropriate alternative. In this context, this work
      presents the methodological development of a new scale to measure the perception
      of air quality, useful as an exposure or risk appraisal metric in public health
      contexts. On the basis of the responses from 2,522 subjects in eight French
      cities, psychometric methods are used to construct the scale from 22 items that
      assess risk perception (anxiety about health and quality of life) and the extent
      to which air pollution is a nuisance (sensorial perception and symptoms). The
      scale is robust, reproducible, and discriminates between subpopulations more
      susceptible to poor air pollution perception. The individual risk factors of poor
      air pollution perception are coherent with those findings in the risk perception
      literature. Perception of air pollution by the general public is a key issue in
      the development of comprehensive risk assessment studies as well as in air
      pollution risk management and policy. This study offers a useful new tool to
      measure such efforts and to help set priorities for air quality improvements in
      combination with air quality measurements.

PMID- 22852803
TI  - Attention please: no affective priming effects in a valent/neutral-categorisation
      task.
AB  - Affective congruency effects in the evaluation task can be explained by either
      spreading of activation or response competition. Eliminating effects of response
      compatibility by using other tasks (semantic categorisation, naming task)
      typically also eliminates affective congruency effects. However, there is no need
      for processing the affective information of the stimuli in these tasks either,
      which could be necessary for an affectively mediated spreading of activation
      (Spruyt et al., 2007, 2009, 2012). We introduced a new task to further test this
      hypothesis. The valent/neutral-categorisation task does not confound affective
      congruency with response compatibility, but still requires a processing of the
      stimuli's valence. No affective congruency effect was obtained with this task in
      two experiments, disfavouring a conditional spreading activation account. On the
      other hand, a significant priming effect was found for associated word pairs in
      Experiment 1, providing evidence for the sensitivity of the task to detect
      spreading activation processes.

PMID- 22852802
TI  - Web-based smoking cessation intervention that transitions from inpatient to
      outpatient: study protocol for a randomized controlled trial.
AB  - BACKGROUND: E-health tools are a new mechanism to expand patient care, allowing
      supplemental resources to usual care, including enhanced patient-provider
      communication. These applications to smoking cessation have yet to be tested in a
      hospitalized patient sample. This project aims to evaluate the effectiveness and
      cost-effectiveness of a tailored web-based and e-message smoking cessation
      program for current smokers that, upon hospital discharge, transitions the
      patient to continue a quit attempt when home (Decide2Quit). DESIGN: A randomized
      two-arm follow-up design will test the effectiveness of an evidence- and
      theoretically-based smoking cessation program designed for post-hospitalization.
      METHODS: A total of 1,488 patients aged 19 or older, who smoked cigarettes in the
      previous 30 days, are being recruited from 27 patient care areas of a large urban
      university hospital. Study-eligible hospitalized patients receiving usual tobacco
      cessation usual care are offered study referral. Trained hospital staff assist
      the 744 patients who are being randomized to the intervention arm with
      registration and orientation to the intervention website. This e-mail and web
      based program offers tailored messages as well as education, self-assessment and
      planning aids, and social support to promote tobacco use cessation. Condition
      blind study staff assess participants for tobacco use history and behaviors,
      tobacco use cost-related information, co-morbidities and psychosocial factors at
      0, 3, 6, and 12 months. The primary outcome is self-reported 30-day tobacco
      abstinence at 6 months follow-up. Secondary outcomes include 7-day point
      prevalence quit rates at 3-, 6-, and 12-month follow-up, 30-day point prevalence
      quit rates at 3 and 12 months, biologically confirmed tobacco abstinence at 6
      month follow-up, and multiple point-prevalence quit rates based on self-reported
      tobacco abstinence rates at each follow-up time period. Healthcare utilization
      and quality of life are assessed at baseline, and 6- and 12-month follow-up to
      measure program cost-effectiveness from the hospital, healthcare payer, patient,
      and societal perspectives. DISCUSSION: Given the impact of tobacco use on medical
      resources, establishing feasible, cost-effective methods for reducing tobacco use
      is imperative. Given the minimal hospital staff burden and the automated
      transition to a post-hospitalization tailored intervention, this program could be
      an easily disseminated approach. TRIAL REGISTRATION: Current Intervention Trial
      NCT01277250.

PMID- 22852804
TI  - Thermosensitive nanoparticles with pH-triggered degradation and release of anti
      inflammatory cell-penetrating peptides.
AB  - Poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) [poly(NIPAm
      AMPS)] nanoparticles can be cross-linked with hydrolytically degradable N,O
      dimethacryloyl hydroxylamine (DMHA) in order to yield a pH-sensitive drug
      delivery system that slowly erodes above pH 5.0. Varying the composition of
      degradable DMHA and nondegradable MBA cross-linking allows for engineered
      variation of particle size and degradation kinetics. Utilizing sulfated comonomer
      AMPS provides for increased passive loading of anti-inflammatory mitogen
      activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell
      penetrating peptide KAFAKLAARLYRKALARQLGVAA (KAFAK) between 24.3% and 29.2% (w/w)
      for nanoparticles with 5 mol % cross-linker. Nanoparticles were shown to be
      nontoxic in vitro and were effective at delivering a therapeutically active dose
      of KAFAK to THP1 human monocytes to suppress tumor necrosis factor alpha (TNF
      alpha) expression during lipopolysaccharide (LPS)-induced inflammation. This
      thermosensitive nanoparticle system is an excellent platform for passive
      diffusive loading in deionized water and release in physiologically relevant
      ionic strength media of environmentally sensitive peptide therapeutics.

PMID- 22852805
TI  - Impact of pre-implant lower urinary tract symptoms on postoperative urinary
      morbidity after permanent prostate brachytherapy.
AB  - OBJECTIVES: To assess the impact of baseline lower urinary tract symptoms on
      postoperative urinary morbidity in patients being treated for prostate cancer
      with 125-I permanent prostate brachytherapy. METHODS: A total of 104 prostate
      cancer patients were enrolled in this study. Their urinary morbidity was followed
      up using the International Prostate Symptom Score and Expanded Prostate Cancer
      Index Composite for 12 months or more after permanent prostate brachytherapy.
      Patients were classified into two groups based on their baseline International
      Prostate Symptom Score: the low International Prostate Symptom Score group (score
      <= 7) and the high International Prostate Symptom Score group (score >= 8).
      Urinary morbidity was estimated in each group based on the results of the
      International Prostate Symptom Score and Expanded Prostate Cancer Index Composite
      measured before permanent prostate brachytherapy, and at 1, 3, 6, 9 and 12 months
      after the end of all radiation therapy. RESULTS: The overall mean total
      International Prostate Symptom Score, International Prostate Symptom Score
      quality of life score, and urinary-related scores for Expanded Prostate Cancer
      Index Composite were significantly worse at 1 month after the end of treatment,
      but they improved gradually after the treatment and recovered to the baseline
      level within 12 months. Even in the high-International Prostate Symptom Score
      group, the International Prostate Symptom Score and International Prostate
      Symptom Score Quality of Life score were significantly worse at 1-3 months after
      permanent prostate brachytherapy, and then recovered to the baseline level
      without prolongation. Although the urination-related Expanded Prostate Cancer
      Index Composite score in the high-International Prostate Symptom Score group was
      significantly worse at 1 month after permanent prostate brachytherapy in
      comparison with that in the low-International Prostate Symptom Score group, it
      recovered to the baseline level without prolongation. CONCLUSIONS: The present
      findings suggest that the presence of lower urinary tract symptoms before
      implantation does not prolong urinary morbidity after permanent prostate
      brachytherapy.

PMID- 22852806
TI  - Microcoil NMR study of the interactions between doxepin, beta-cyclodextrin, and
      acetate during capillary isotachophoresis.
AB  - The capillary isotachophoresis (cITP) separation of the isomers of the tricyclic
      antidepressant doxepin using beta-cyclodextrin (beta-CD) as a buffer additive is
      investigated by online microcoil NMR detection. Capillary electrophoresis (CE) is
      also used to determine the binding constant between the doxepin E and Z geometric
      isomers and beta-CD. Although the doxepin isomers could be easily baseline
      resolved by CE, their separation by cITP was more challenging due in part to the
      high concentration of doxepin after cITP-focusing. The use of online (1)H NMR
      detection allows observation of changes in doxepin dynamics due to formation of
      the beta-CD inclusion complex, changes in the fraction complexed and the
      intracapillary pH. It also provides novel experimental evidence that a weak
      complex between beta-CD and acetate contributes to its active transport from the
      leading electrolyte through the sample band to the trailing electrolyte in this
      cationic cITP separation. The results of these cITP-NMR experiments provide new
      mechanistic details about the interactions of the buffer counterion acetate with
      various components of the separation system and have important implications for
      other analyses based on formation of cyclodextrin inclusion complexes.

PMID- 22852807
TI  - Cellulases belonging to glycoside hydrolase families 6 and 7 contribute to the
      virulence of Magnaporthe oryzae.
AB  - Upon infection, phytopathogenic fungi secrete an array of hydrolytic enzymes that
      can degrade components of the host epidermis, including waxes, the cuticle, and
      cell walls. Cellulases, which can hydrolyze crystalline cellulose in the plant
      cell wall, are among these hydrolytic enzymes. Here, we provide RNAi-based
      evidence to show that cellulases belonging to glycosyl hydrolase (GH) families 6
      and 7 contribute to the penetration of the host epidermis and further invasion by
      the phytopathogenic fungus Magnaporthe oryzae. The GH6 and GH7 cellulases likely
      include all members of the cellobiohydrolase family and some endoglucanases in M.
      oryzae. Quantitative reverse-transcriptase polymerase chain reaction analysis
      indicated that more than half of the cellulases were highly induced during
      infection. We constructed knock-down (KD) mutants of these cellulases using the
      building blocks method we reported previously. The transcript levels of the
      target genes and cellulase activity were considerably reduced in the KD mutants.
      The KD mutants resulted in fewer lesions, less penetration, and infection of
      fewer cells compared with the parent strain. Cytological analyses showed that a
      high rate of papilla formation blocked invasion of the KD mutants into host
      cells. These results suggest that the GH6 and GH7 cellulases play roles in the
      virulence of M. oryzae.

PMID- 22852808
TI  - RCY1-mediated resistance to Cucumber mosaic virus is regulated by LRR domain
      mediated interaction with CMV(Y) following degradation of RCY1.
AB  - RCY1, which encodes a coiled coil nucleotide-binding site leucine-rich repeat
      (LRR) class R protein, confers the hypersensitive response (HR) to a yellow
      strain of Cucumber mosaic virus (CMV[Y]) in Arabidopsis thaliana. Nicotiana
      benthamiana transformed with hemagglutinin (HA) epitope-tagged RCY1 (RCY1-HA)
      also exhibited a defense response accompanied by HR cell death and induction of
      defense-related gene expression in response to CMV(Y). Following transient
      expression of RCY1-HA by agroinfiltration, the defense reaction was induced in N.
      benthamiana leaves infected with CMV(Y) but not in virulent CMV(B2)-infected N.
      benthamiana leaves transiently expressing RCY1-HA or CMV(Y)-infected N.
      benthamiana leaves transiently expressing HA-tagged RPP8 (RPP8-HA), which is
      allelic to RCY1. This result suggests that Arabidopsis RCY1-conferred resistance
      to CMV(Y) could be reproduced in N. benthamiana leaves in a gene-for-gene manner.
      Expression of a series of chimeric constructs between RCY1-HA and RPP8-HA in
      CMV(Y)-infected N. benthamiana indicated that induction of defense responses to
      CMV(Y) is regulated by the LRR domain of RCY1. Interestingly, in CMV(Y)-infected
      N. benthamiana manifesting the defense response, the levels of both RCY1 and
      chimeric proteins harboring the RCY1 LRR domain were significantly reduced. Taken
      together, these data indicate that the RCY1-conferred resistance response to
      CMV(Y) is regulated by an LRR domain-mediated interaction with CMV(Y) and seems
      to be tightly associated with the degradation of RCY1 in response to CMV(Y).

PMID- 22852809
TI  - Indole-3-acetaldoxime-derived compounds restrict root colonization in the
      beneficial interaction between Arabidopsis roots and the endophyte Piriformospora
      indica.
AB  - The growth-promoting and root-colonizing endophyte Piriformospora indica induces
      camalexin and the expression of CYP79B2, CYP79B3, CYP71A13, PAD3, and WRKY33
      required for the synthesis of indole-3-acetaldoxime (IAOx)-derived compounds in
      the roots of Arabidopsis seedlings. Upregulation of the mRNA levels by P. indica
      requires cytoplasmic calcium elevation and mitogen-activated protein kinase 3 but
      not root-hair-deficient 2, radical oxygen production, or the 3-phosphoinositide
      dependent kinase 1/oxidative signal-inducible 1 pathway. Because P. indica
      mediated growth promotion is impaired in cyp79B2 cyp79B3 seedlings, while pad3
      seedlings-which do not accumulate camalexin-still respond to the fungus, IAOx
      derived compounds other than camalexin (e.g., indole glucosinolates) are required
      during early phases of the beneficial interaction. The roots of cyp79B2 cyp79B3
      seedlings are more colonized than wild-type roots, and upregulation of the
      defense genes pathogenesis-related (PR)-1, PR-3, PDF1.2, phenylalanine ammonia
      lyase, and germin indicates that the mutant responds to the lack of IAOx-derived
      compounds by activating other defense processes. After 6 weeks on soil, defense
      genes are no longer upregulated in wild-type, cyp79B2 cyp79B3, and pad3 roots.
      This results in uncontrolled fungal growth in the mutant roots and reduced
      performance of the mutants. We propose that a long-term harmony between the two
      symbionts requires restriction of root colonization by IAOx-derived compounds.

PMID- 22852810
TI  - Regulation of biosynthesis of syringolin A, a Pseudomonas syringae virulence
      factor targeting the host proteasome.
AB  - Many strains of the phytopathogenic bacterium Pseudomonas syringae pv. syringae
      synthesize the virulence factor syringolin A, which irreversibly inactivates the
      eukaryotic proteasome. Syringolin A, a peptide derivative, is synthesized by a
      mixed nonribosomal peptide/polyketide synthetase encoded by five clustered genes,
      sylA to sylE. Biosynthesis of syringolin A, previously shown to be dependent on
      the GacS/GacA two-component system, occurs in planta and in vitro but only under
      still culture conditions in a defined medium. Here, we show that the sylC, sylD,
      and sylE genes of P. syringae pv. syringae B301D-R form an operon transcribed by
      promoter sequences located between the sylCDE operon and the sylB gene residing
      on opposite strands. Assays of overlapping sylB and sylCDE promoter deletions
      translationally fused to the lacZ gene defined promoter sequences required for
      gene activity both in vitro and in planta. Activation of both promoters depended
      on the sylA gene encoding a helix-turn-helix (HTH) LuxR-type transcription factor
      which was shown to directly bind to the promoters. Activity of the sylA gene, in
      turn, required a functional salA gene, which also encodes an HTH LuxR-type
      transcription factor. Furthermore, evidence is presented that acyl-homoserine
      lactone-mediated quorum-sensing regulation is not involved in syringolin A
      biosynthesis but that oxygen concentration appears to play a role.

PMID- 22852811
TI  - Novel mutations affecting the secondary structure of MT-RNR1 gene: a causal
      relationship with profound nonsyndromic hearing impairment.
AB  - Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of
      sensorineural hearing loss, especially in the MT-RNR1 gene. In the present study
      we have performed mutational screening for m.1555A>G and a region of the MT-RNR1
      gene in 303 unrelated patients (including family members of 25 probands) with
      nonsyndromic hearing loss and 200 controls. Three homoplasmic variants, namely,
      m.1453A>G, 1462G>A, and 1508C>T, were identified in addition to the known
      deafness-associated m.1555A>G mutation in the MT-RNR1 gene. All the variants were
      detected only in the patients and not in the controls. m.1555A>G was detected in
      three probands amounting to 1.0%. Prediction of RNA secondary structure showed
      changes in all the three variants, the most severe being in m.1453A>G that was
      inherited in a typical maternal pattern in two families. Screening of GJB2 and
      GJB6 genes in all these probands revealed cosegregation of the p.W24X mutation
      (GJB2) in one family with m.1453A>G. Only the proband carrying the p.W24X
      mutation in a homozygous state expressed the condition while heterozygous and
      normal homozygous relatives had normal hearing in spite of having the mutation in
      MT-RNR1. The conservation index (CI) of m.1453A>G was found to be 82%, suggesting
      it to be a possibly deleterious mutation. Functional studies using cell lines
      derived from muscle tissue of these patients may reveal the pathogenic mechanism
      of deafness in them.

PMID- 22852812
TI  - Toxicology of smokeless tobacco: implications for immune, reproductive, and
      cardiovascular systems.
AB  - The popularity of smokeless tobacco (ST), or noncombusted tobacco, usually placed
      within the mouth to be chewed, sucked, or swallowed, is growing rapidly and its
      prevalence of use is rising globally, due (in part) to greater convenience, as
      allowable cigarette smoking areas are rapidly decreasing, and increased social
      acceptability. Though data are limited, ST usage has been directly linked to a
      number of adverse health outcomes. The potential role that immune dysfunction,
      including dysregulation of immune cells and their components, may play in the
      progression of these adverse health outcomes is only just beginning to emerge.
      Evidence suggesting reproductive outcomes, such as perinatal mortality, preterm
      birth, and reduced sperm viability, also exists in conjunction with ST use.
      Cardiovascular health may also be impacted by ST use, resulting in increased
      blood pressure and endothelial dysfunction, both of which may potentially lead to
      cardiovascular diseases. This review describes the toxicological implications
      associated with ST use, with emphasis on immune, reproductive, and cardiovascular
      outcomes. Epidemiological studies are discussed with respect to experimental
      studies to help develop the relationship between ST and disease pathology. This
      review also summarizes the gaps in ST knowledge and potential future directions
      that are needed to more fully delineate the complex systems driving the adverse
      health outcomes associated with its use.

PMID- 22852813
TI  - Environmental radon exposure and childhood leukemia.
AB  - Despite the fact that animal and human epidemiological studies confirmed a link
      between radon exposure in homes and increased risk of lung cancer in general
      population, other types of cancers induced by radon, such as leukemia, have not
      been consistently demonstrated. The aim of this review was to summarize data
      published thus far from ecological and case-control studies in exposed
      populations, taking into account radon dose estimation and evidence of radon
      induced genotoxicity, in an effort to clarify the correlation between home radon
      exposure and incidence of childhood leukemia. Among 12 ecological studies, 11
      reported a positive association between radon levels and elevated frequency of
      childhood leukemia, with 8 being significant. In conjunction with ecological
      studies, several case-control studies on indoor radon exposure and childhood
      leukemia were examined, and most investigations indicated a weak association with
      only a few showing significance. A major source of uncertainty in radon risk
      assessment is radon dose estimate. Methods for radon exposure measurement in
      homes of children are one of the factors that affect the risk estimates in a case
      control study. The effects of radon-induced genetic damage were studied both in
      vitro and in vivo using genetic endpoints including chromosomal aberration (CA),
      micronuclei (MN) formation, gene mutation, and deletions and insertions. By
      applying a meta-analysis, an increased risk of childhood leukemia induced by
      indoor radon exposure was noted for overall leukemia and for acute lymphoblastic
      leukemia (ALL). Data thus indicated an association between environmental radon
      exposure and elevated leukemia incidence, but more evidence is required in both
      human investigations and animal mechanistic research before this assumption may
      be confirmed with certainty.

PMID- 22852815
TI  - Secondary hemophagocytic lymphohistiocytosis: forget me not!

PMID- 22852814
TI  - Potential for effects of land contamination on human health. 1.The case of
      cadmium.
AB  - A review of the epidemiological literature on the potential effects of land
      contamination shows that the largest body of contaminant-specific research
      relates to cadmium (Cd). First, a brief outline of the key issues related to the
      study of health impact of land contamination is presented. The recent literature
      is then reviewed for evidence of associations and possible causal relationships
      between exposure to Cd from land contamination and health impact. A large number
      of studies focusing on Cd arise because of the ready availability of biomarkers
      of exposure and effect and the demonstrated link between soil Cd and itai-itai
      disease (severe renal and bone disorders) via dietary exposure in Japan and
      China. Where dietary differences yield lower exposures, links have been
      established between Cd in soil and biomarkers of renal or bone dysfunctions, but
      not to health impacts per se. Potential effects of Cd exposure were also
      investigated for other health outcomes, including hypertension, cancer incidence,
      preterm delivery, and semen parameters. In contrast to renal and bone disorders,
      results are generally inconsistent and require further lines of evidence.
      Residence in locations with elevated concentrations of Cd in soil is a poor
      surrogate for exposure, and there are examples where residents in locations with
      elevated concentrations of Cd in soil did not appear to suffer serious health
      consequences.

PMID- 22852816
TI  - Interpreting the results of a modified gravity model: examining access to primary
      health care physicians in five Canadian provinces and territories.
AB  - BACKGROUND: Primary health care (PHC) encompasses an array of health and social
      services that focus on preventative, diagnostic, and basic care measures to
      maintain wellbeing and address illnesses. In Canada, PHC involves the provision
      of first-contact health care services by providers such as family physicians and
      general practitioners - collectively referred as PHC physicians here. Ensuring
      access is a key requirement of effective PHC delivery. This is because having
      access to PHC has been shown to positively impact a number of health outcomes.
      METHODS: We build on recent innovations in measuring potential spatial access to
      PHC physicians using geographic information systems (GIS) by running and then
      interpreting the findings of a modified gravity model. Elsewhere we have
      introduced the protocol for this model. In this article we run it for five
      selected Canadian provinces and territories. Our objectives are to present the
      results of the modified gravity model in order to: (1) understand how potential
      spatial access to PHC physicians can be interpreted in these Canadian
      jurisdictions, and (2) provide guidance regarding how findings of the modified
      gravity model should be interpreted in other analyses. RESULTS: Regarding the
      first objective, two distinct spatial patterns emerge regarding potential spatial
      access to PHC physicians in the five selected Canadian provinces: (1) a clear
      north-south pattern, where southern areas have greater potential spatial access
      than northern areas; and (2) while gradients of potential spatial access exist in
      and around urban areas, access outside of densely-to-moderately populated areas
      is fairly binary. Regarding the second objective, we identify three principles
      that others can use to interpret the findings of the modified gravity model when
      used in other research contexts. CONCLUSIONS: Future applications of the modified
      gravity model are needed in order to refine the recommendations we provide on
      interpreting its results. It is important that studies are undertaken that can
      help administrators, policy-makers, researchers, and others with characterizing
      the state of access to PHC, including potential spatial access. We encourage
      further research to be done using GIS in order to offer new, spatial perspectives
      on issues of access to health services given the increased recognition that the
      place-based nature of health services can benefit from the use of the
      capabilities of GIS to enhance the role that visualization plays in decision
      making.

PMID- 22852818
TI  - Selective oxidative degradation of organic pollutants by singlet oxygen-mediated
      photosensitization: tin porphyrin versus C60 aminofullerene systems.
AB  - This study evaluates the potential application of tin porphyrin- and C(60)
      aminofullerene-derivatized silica (SnP/silica and aminoC(60)/silica) as (1)O(2)
      generating systems for photochemical degradation of organic pollutants.
      Photosensitized (1)O(2) production with SnP/silica, which was faster than with
      aminoC(60)/silica, effectively oxidized a variety of pharmaceuticals. Significant
      degradation of pharmaceuticals in the presence of the 400-nm UV cutoff filter
      corroborated visible light activation of both photosensitizers. Whereas the
      efficacy of aminoC(60)/silica for (1)O(2) production drastically decreased under
      irradiation with lambda > 550 nm, Q-band absorption caused negligible loss of the
      photosensitizing activity of SnP/silica in the long wavelength region. Faster
      destruction of phenolates by SnP/silica and aminoC(60)/silica under alkaline pH
      conditions further implicated (1)O(2) involvement in the oxidative degradation.
      Direct charge transfer mediated by SnP, which was inferred from nanosecond laser
      flash photolysis, induced significant degradation of neutral phenols under high
      power light irradiation. Self-sensitized destruction caused gradual activity loss
      of SnP/silica in reuse tests unlike aminoC(60)/silica. The kinetic comparison of
      SnP/silica and TiO(2) photocatalyst in real wastewater effluents showed that
      photosensitized singlet oxygenation of pharmaceuticals was still efficiently
      achieved in the presence of background organic matters, while significant
      interference was observed for photocatalyzed oxidation involving non-selective OH
      radical.

PMID- 22852819
TI  - Porous SnS nanorods/carbon hybrid materials as highly stable and high capacity
      anode for Li-ion batteries.
AB  - A new solid-liquid-gas-solid (SLGS) growth strategy has been exploited to prepare
      porous SnS nanorods directly on carbon hybrid nanostructure by using a sulfur
      containing resin (s-resin) laden with crystalline SnO(2) nanoparticles and
      subsequent calcination promoted the development of porous SnS nanorods growing on
      carbon. As an anode material in Li-ion batteries (LIBs), SnS nanorods/C hybrid
      materials show highly stable and high capacity retention rate, which suggest that
      the novel hybrid materials have alluring prospect for electrochemical energy
      storage applications.

PMID- 22852820
TI  - Healthy lifestyles for adults with intellectual disability: knowledge, barriers,
      and facilitators.
AB  - BACKGROUND: People with intellectual disability (ID) are more likely to have
      health problems than people without disability. Little previous research has
      investigated health from the perspective of the people with ID themselves. We
      aimed to focus on what people with ID understand being healthy to mean and what
      their experiences are of healthy lifestyles. METHOD: Semistructured interviews
      were conducted with 13 adults with ID to ask them about their health and healthy
      lifestyles. Data were analysed thematically. RESULTS: Participants demonstrated
      understanding of what it means to be healthy, have a healthy diet, the dangers of
      substance misuse, and the benefits of exercise. Participants demonstrated some
      knowledge about rationales for engaging in healthy behaviours. The idea of
      moderation was raised, along with barriers and facilitators to engaging in a
      healthy lifestyle. CONCLUSIONS: Findings suggest that people with ID demonstrate
      some understanding of what constitutes being healthy and are aware of healthy
      lifestyles, the consequences of unhealthy behaviours, and of the need for
      moderation.

PMID- 22852821
TI  - Bio-Rad's Bio-Plex(r) suspension array system, xMAP technology overview.
AB  - The Bio-Plex((r)) system utilizes xMAP technology to permit the multiplexing of
      up to 100 different analytes. Multiplex analysis gives researchers the ability to
      look at analytes simultaneously providing more information from less sample
      volume in less time than traditional immunoassay methods. Similar to ELISA, xMAP
      utilizes an antibody sandwich for detection but differs from ELISA in capture
      substrate and detection method. Rather than a flat surface, Bio-Plex((r)) assays
      make use of differentially detectable bead sets as a substrate capturing analytes
      in solution and employs fluorescent methods for detection. These bead sets
      identify the analytes and detection antibodies are used to measure the quantity
      of analyte. The use of differentially detectable beads enables the simultaneous
      identification and quantification of many analytes in the same sample.

PMID- 22852822
TI  - E versus Z diazeniumdiolation of acetoacetate-derived carbanions.
AB  - Nitric oxide adds to methyl acetoacetate in the presence of KOH in methanol at
      room temperature to form potassium acetylsydnonate N-oxide (K1) with an (E)
      diazeniumdiolation and potassium acetate diazenium diolate (K(2)2) from a (Z)
      diazeniumdiolation. A study of the reaction with LiOH, NaOH, and NMe(4)OH and
      with ethyl acetate substrate reveals that the temperature of the reaction greatly
      influences the nitric oxide reactivity. At 23  degrees C, nitric oxide adds to
      give both E and Z products, whereas at -5  degrees C the gas reacts almost
      exclusively to give Z addition. The (Z)-diazeniumdiolation products, namely, the
      alkali metal and NMe(4)(+) salts of methyl and ethylbutenoate-2-diazeniumdiolate
      3-hydroxylate (3(2-) and 4(2-)), are isolated in good yields. The alkali metal
      salts are not amenable for recrystallization because of their ready decomposition
      in aqueous solutions. However, [NMe(4)](2)[MeC(O)C(N(2)O(2))CO(2)Me] is readily
      recrystallized from a methanol/acetonitrile solvent mixture. The crystals are
      unambiguously characterized by X-ray crystallography. NMR spectra for all of the
      3(2-) and 4(2-) salts reveal the presence of two isomers in aq solutions. But the
      structure of the NMe(4)(+) salt contains only one of the isomers. Our attempts to
      cyclize the isolated and purified butenoatediazeniumdiolates from the (Z)
      diazeniumdiolation to the E-containing sydnonate products were unsuccessful.
      TGA/DSC data for all of the products demonstrate the thermal instability of the
      salts at high temperatures. The salts decompose exothermally possibly with the
      release of N(2)O among other gases.

PMID- 22852817
TI  - A systems biology approach to the global analysis of transcription factors in
      colorectal cancer.
AB  - BACKGROUND: Biological entities do not perform in isolation, and often, it is the
      nature and degree of interactions among numerous biological entities which
      ultimately determines any final outcome. Hence, experimental data on any single
      biological entity can be of limited value when considered only in isolation. To
      address this, we propose that augmenting individual entity data with the
      literature will not only better define the entity's own significance but also
      uncover relationships with novel biological entities.To test this notion, we
      developed a comprehensive text mining and computational methodology that focused
      on discovering new targets of one class of molecular entities, transcription
      factors (TF), within one particular disease, colorectal cancer (CRC). METHODS: We
      used 39 molecular entities known to be associated with CRC along with six
      colorectal cancer terms as the bait list, or list of search terms, for mining the
      biomedical literature to identify CRC-specific genes and proteins. Using the
      literature-mined data, we constructed a global TF interaction network for CRC. We
      then developed a multi-level, multi-parametric methodology to identify TFs to
      CRC. RESULTS: The small bait list, when augmented with literature-mined data,
      identified a large number of biological entities associated with CRC. The
      relative importance of these TF and their associated modules was identified using
      functional and topological features. Additional validation of these highly-ranked
      TF using the literature strengthened our findings. Some of the novel TF that we
      identified were: SLUG, RUNX1, IRF1, HIF1A, ATF-2, ABL1, ELK-1 and GATA-1. Some of
      these TFs are associated with functional modules in known pathways of CRC,
      including the Beta-catenin/development, immune response, transcription, and DNA
      damage pathways. CONCLUSIONS: Our methodology of using text mining data and a
      multi-level, multi-parameter scoring technique was able to identify both known
      and novel TF that have roles in CRC. Starting with just one TF (SMAD3) in the
      bait list, the literature mining process identified an additional 116 CRC
      associated TFs. Our network-based analysis showed that these TFs all belonged to
      any of 13 major functional groups that are known to play important roles in CRC.
      Among these identified TFs, we obtained a novel six-node module consisting of
      ATF2-P53-JNK1-ELK1-EPHB2-HIF1A, from which the novel JNK1-ELK1 association could
      potentially be a significant marker for CRC.

PMID- 22852824
TI  - Pacemaker and radiotherapy in breast cancer: is targeted intraoperative
      radiotherapy the answer in this setting?
AB  - We present the case of an 83 year old woman with a cardiac pacemaker located
      close in distance to a subsequently diagnosed invasive ductal carcinoma of the
      left breast. Short range intraoperative radiotherapy was given following wide
      local excision and sentinel node biopsy. The challenges of using ionising
      radiation with pacemakers is also discussed.

PMID- 22852825
TI  - Chemical manipulation of magnetic ordering in Mn(1-x)Sn(x)Bi2Se4 solid-solutions.
AB  - Several compositions of manganese-tin-bismuth selenide solid-solution series,
      Mn(1-x)Sn(x)Bi(2)Se(4) (x = 0, 0.3, 0.75), were synthesized by combining high
      purity elements in the desired ratio at moderate temperatures. X-ray single
      crystal studies of a Mn-rich composition (x = 0) and a Mn-poor phase (x = 0.75)
      at 100 and 300 K revealed that the compounds crystallize isostructurally in the
      monoclinic space group C2/m (no.12) and adopt the MnSb(2)Se(4) structure type.
      Direct current (DC) magnetic susceptibility measurements in the temperature range
      from 2 to 300 K indicated that the dominant magnetic ordering within the Mn(1
      x)Sn(x)Bi(2)Se(4) solid-solutions below 50 K switches from antiferromagnetic
      (AFM) for MnBi(2)Se(4) (x = 0), to ferromagnetic (FM) for
      Mn(0.7)Sn(0.3)Bi(2)Se(4) (x = 0.3), and finally to paramagnetic (PM) for
      Mn(0.25)Sn(0.75)Bi(2)Se(4) (x = 0.75). We show that this striking variation in
      the nature of magnetic ordering within the Mn(1-x)Sn(x)Bi(2)Se(4) solid-solution
      series can be rationalized by taking into account: (1) changes in the
      distribution of magnetic centers within the structure arising from the Mn to Sn
      substitutions, (2) the contributions of spin-polarized free charge carriers
      resulting from the intermixing of Mn and Sn within the same crystallographic
      site, and (3) a possible long-range ordering of Mn and Sn atoms within individual
      {M}(n)Se(4n+2) single chain leading to quasi isolated {MnSe(6)} octahedra spaced
      by nonmagnetic {SnSe(6)} octahedra.

PMID- 22852823
TI  - Upregulation of transmitter release probability improves a conversion of synaptic
      analogue signals into neuronal digital spikes.
AB  - Action potentials at the neurons and graded signals at the synapses are primary
      codes in the brain. In terms of their functional interaction, the studies were
      focused on the influence of presynaptic spike patterns on synaptic activities.
      How the synapse dynamics quantitatively regulates the encoding of postsynaptic
      digital spikes remains unclear. We investigated this question at unitary
      glutamatergic synapses on cortical GABAergic neurons, especially the quantitative
      influences of release probability on synapse dynamics and neuronal encoding.
      Glutamate release probability and synaptic strength are proportionally
      upregulated by presynaptic sequential spikes. The upregulation of release
      probability and the efficiency of probability-driven synaptic facilitation are
      strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation
      of release probability improves spike capacity and timing precision at
      postsynaptic neuron. These results suggest that the upregulation of presynaptic
      glutamate release facilitates a conversion of synaptic analogue signals into
      digital spikes in postsynaptic neurons, i.e., a functional compatibility between
      presynaptic and postsynaptic partners.

PMID- 22852826
TI  - Interpersonal dynamics and relative positioning to scoring target of performers
      in 1 vs. 1 sub-phases of team sports.
AB  - In this study, we examined the effects of relative positioning of attacker
      defender dyads to the basket on interpersonal coordination tendencies in
      basketball. To achieve this aim, four right-hand dominant basketball players
      performed in a 1 vs. 1 sub-phase, at nine different playing locations relative to
      the basket (from 0 degrees  to 180 degrees , in 20 degrees  increments).
      Performers' movement displacement trajectories were video-recorded and digitized
      in 162 trials. Results showed that interpersonal coordination tendencies changed
      according to the scaling of the relative position of performers to the basket.
      Stable in-phase modes of coordination were observed between performers'
      longitudinal and lateral displacements (50.47% and 43.02%) on the left side of
      the court. On the right side of the court, a shift in the dominant mode of
      coordination was observed to a defender lead-lag of -30 degrees , both for
      longitudinal and lateral displacements (30.51% and 32.65%). These results suggest
      how information about dribbler hand dominance and relative position to the basket
      may have constrained attacker-defender coordination tendencies in 1 vs. 1 sub
      phases of basketball.

PMID- 22852827
TI  - Health, well-being, and measuring the burden of disease.
AB  - This essay asks whether the global burden of diseases, injuries, and risk
      factors (GBD) should be measured in terms of their consequences for health, as
      maintained by most of those who are attempting to measure the GBD, or in terms of
      their consequences for well-being, as argued by John Broome. It answers that the
      burden of disease should be understood in terms of the consequences of disease
      for health, and it defends the wider efforts to measure health by those who are
      in other ways skeptical of the project of measuring the GBD.

PMID- 22852828
TI  - Phenotypic and histochemical traits of the interaction between Plasmopara
      viticola and resistant or susceptible grapevine varieties.
AB  - BACKGROUND: Grapevine downy mildew, caused by Plasmopara viticola, is a very
      serious disease affecting mainly Vitis vinifera cultivated varieties around the
      world. Breeding for resistance through the crossing with less susceptible species
      is one of the possible means to reduce the disease incidence and the application
      of fungicides. The hybrid Bianca and some of its siblings are considered very
      promising but their resistance level can vary depending on the pathogen strain.
      Moreover, virulent strains characterized by high fitness can represent a
      potential threat to the hybrid cultivation. RESULTS: The host response and the
      pathogen virulence were quantitatively assessed by artificially inoculating cv
      Chardonnay, cv Bianca and their siblings with P. viticola isolates derived from
      single germinating oospores collected in various Italian viticultural areas. The
      host phenotypes were classified as susceptible, intermediate and resistant,
      according to the Area Under the Disease Progress Curve caused by the inoculated
      strain. Host responses in cv Bianca and its siblings significantly varied
      depending on the P. viticola isolates, which in turn differed in their virulence
      levels. The fitness of the most virulent strain did not significantly vary on the
      different hybrids including Bianca in comparison with the susceptible cv
      Chardonnay, suggesting that no costs are associated with virulence. Among the
      individual fitness components, only sporangia production was significantly
      reduced in cv Bianca and in some hybrids. Comparative histological analysis
      revealed differences between susceptible and resistant plants in the pathogen
      diffusion and cytology from 48 h after inoculation onwards. Defence mechanisms
      included callose depositions in the infected stomata, increase in peroxidase
      activity, synthesis of phenolic compounds and flavonoids and the necrosis of
      stomata and cells immediately surrounding the point of invasion and determined
      alterations in the size of the infected areas and in the number of sporangia
      differentiated. CONCLUSIONS: Some hybrids were able to maintain an intermediate
      resistant behaviour even when inoculated with the most virulent strain. Such
      hybrids should be considered for further field trials.

PMID- 22852829
TI  - Decatungstate as photoredox catalyst: benzylation of electron-poor olefins.
AB  - Excited tetrabutylammonium decatungstate (TBADT), known to activate a variety of
      compounds via hydrogen atom transfer (HAT), has now been applied as a photoredox
      catalyst for the effective oxidative cleavage of benzyl silanes and radical
      benzylation of reducible olefins occurring in isolated yields from poor to
      excellent.

PMID- 22852830
TI  - Socioeconomic inequalities in lipid and glucose metabolism in early childhood in
      a population-based cohort: the ABCD-Study.
AB  - BACKGROUND: Socioeconomic inequalities in cardiovascular disease are pervasive,
      yet much remains to be understood about how they originate. The objective of this
      study was to explore the relations of socioeconomic status to lipid and glucose
      metabolism as indicators of cardiovascular health in 5-6 year olds. Additionally
      to explore the explanatory role of maternal factors, birth outcome, and child
      factors. METHODS: In 1308 5-6 year old ethnic Dutch children from the ABCD cohort
      study, lipids (cholesterol, LDL, HDL, triglycerides), glucose and C-peptide were
      measured after an overnight-fast. RESULTS: There were no differences in
      cholesterol, HDL, LDL, and triglycerides between socioeconomic groups, as
      indicated by maternal education and income adequacy. However, children of low
      educated mothers had on average a higher glucose (beta = 0.15; 95% confidence
      interval (CI) 0.03 - 0.27), logC-peptide (beta = 0.07; 95% CI 0.04 - 0.09), and
      calculated insulin resistance (HOMA-IR) (beta = 0.15; 95% CI 0.08 - 0.22)
      compared to children of high educated mothers. Only childhood BMI partly
      explained these differences (models controlled for age, height, and sex).
      CONCLUSIONS: The socioeconomic gradient in cardiovascular risk factors seems to
      emerge in early childhood. In absence of underlying mechanisms these empirical
      findings are relevant for public health care and further explanatory research.

PMID- 22852831
TI  - The mate recognition protein gene mediates reproductive isolation and speciation
      in the Brachionus plicatilis cryptic species complex.
AB  - BACKGROUND: Chemically mediated prezygotic barriers to reproduction likely play
      an important role in speciation. In facultatively sexual monogonont rotifers from
      the Brachionus plicatilis cryptic species complex, mate recognition of females by
      males is mediated by the Mate Recognition Protein (MRP), a globular glycoprotein
      on the surface of females, encoded by the mmr-b gene family. In this study, we
      sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B.
      plicatilis species complex, examined the mode of evolution and selection of mmr
      b, and determined the relationship between mmr-b genetic distance and mate
      recognition among isolates. RESULTS: Isolates of the B. plicatilis species
      complex have 1-4 copies of mmr-b, each composed of 2-9 nearly identical tandem
      repeats. The repeats within a gene copy are generally more similar than are gene
      copies among phylotypes, suggesting concerted evolution. Compared to housekeeping
      genes from the same isolates, mmr-b has accumulated only half as many synonymous
      differences but twice as many non-synonymous differences. Most of the amino acid
      differences between repeats appear to occur on the outer face of the protein, and
      these often result in changes in predicted patterns of phosphorylation. However,
      we found no evidence of positive selection driving these differences. Isolates
      with the most divergent copies were unable to mate with other isolates and rarely
      self-crossed. Overall the degree of mate recognition was significantly correlated
      with the genetic distance of mmr-b. CONCLUSIONS: Discrimination of compatible
      mates in the B. plicatilis species complex is determined by proteins encoded by
      closely related copies of a single gene, mmr-b. While concerted evolution of the
      tandem repeats in mmr-b may function to maintain identity, it can also lead to
      the rapid spread of a mutation through all copies in the genome and thus to
      reproductive isolation. The mmr-b gene is evolving rapidly, and novel alleles may
      be maintained and increase in frequency via asexual reproduction. Our analyses
      indicate that mate recognition, controlled by MMR-B, may drive reproductive
      isolation and allow saltational sympatric speciation within the B. plicatilis
      cryptic species complex, and that this process may be largely neutral.

PMID- 22852833
TI  - Validity of the 'protocol of oro-facial myofunctional evaluation with scores' for
      young and adult subjects.
AB  - The aims of this study were to analyse the validity, sensitivity and specificity
      of the protocol of oro-facial myofunctional evaluation with scores (OMES) for oro
      facial myofunctional disorder (OMD) diagnosis in young and adult subjects. Eighty
      subjects were examined. The OMES was validated against the Nordic orofacial test
      screening (NOT-S) protocol (criterion validity) (Spearman correlation test). The
      construct validity was tested by analysis of the ability of the OMES (i) to
      differentiate healthy subjects (n = 22) from temporomandibular disorder (TMD)
      patients (n = 22), which frequently have OMD (Mann-Whitney test) and (ii) to
      measure the changes that occurred in a subgroup with TMD between the period
      before and after oro-facial myofunctional therapy (T group, n = 15) (Wilcoxon
      test). Two speech therapists trained with the OMES participated as examiners (E).
      There was a statistically significant correlation between the OMES and NOT-S
      protocols, which was negative because the two scales are inverse (r = -0.86, P <
      0.01). There was a significant difference between the healthy and TMD subjects
      regarding the oro-facial myofunctional status (OMES total score, P = 0.003).
      After therapy, the T group showed improvement in the oro-facial myofunctional
      status (OMES total score, P = 0.001). Inter- and intra-examiner agreement was
      moderate, and the reliability coefficients ranged from good to excellent. The
      OMES protocol presented mean sensitivity and specificity = 0.80, positive
      predictive value = 0.76 and negative predictive value = 0.84. CONCLUSION: The
      OMES protocol is valid and reliable for clinical evaluation of young and adult
      subjects, among them patients with TMD.

PMID- 22852832
TI  - Comparative effectiveness of post-discharge interventions for hospitalized
      smokers: study protocol for a randomized controlled trial.
AB  - BACKGROUND: A hospital admission offers smokers an opportunity to quit. Smoking
      cessation counseling provided in the hospital is effective, but only if it
      continues for more than one month after discharge. Providing smoking cessation
      medication at discharge may add benefit to counseling. A major barrier to
      translating this research into clinical practice is sustaining treatment during
      the transition to outpatient care. An evidence-based, practical, cost-effective
      model that facilitates the continuation of tobacco treatment after discharge is
      needed. This paper describes the design of a comparative effectiveness trial
      testing a hospital-initiated intervention against standard care. METHODS/DESIGN:
      A two-arm randomized controlled trial compares the effectiveness of standard post
      discharge care with a multi-component smoking cessation intervention provided for
      three months after discharge. Current smokers admitted to Massachusetts General
      Hospital who receive bedside smoking cessation counseling, intend to quit after
      discharge and are willing to consider smoking cessation medication are eligible.
      Study participants are recruited following the hospital counseling visit and
      randomly assigned to receive Standard Care or Extended Care after hospital
      discharge. Standard Care includes a recommendation for a smoking cessation
      medication and information about community resources. Extended Care includes up
      to three months of free FDA-approved smoking cessation medication and five
      proactive computerized telephone calls that use interactive voice response
      technology to provide tailored motivational messages, offer additional live
      telephone counseling calls from a smoking cessation counselor, and facilitate
      medication refills. Outcomes are assessed at one, three, and six months after
      hospital discharge. The primary outcomes are self-reported and validated seven
      day point prevalence tobacco abstinence at six months. Other outcomes include
      short-term and sustained smoking cessation, post-discharge utilization of smoking
      cessation treatment, hospital readmissions and emergency room visits, and program
      cost per quit. DISCUSSION: This study tests a disseminable smoking intervention
      model for hospitalized smokers. If effective and widely adopted, it could help to
      reduce population smoking rates and thereby reduce tobacco-related mortality,
      morbidity, and health care costs. TRIAL REGISTRATION: United States Clinical
      Trials Registry NCT01177176.

PMID- 22852834
TI  - Dissemination of the nurse-administered Tobacco Tactics intervention versus usual
      care in six Trinity community hospitals: study protocol for a comparative
      effectiveness trial.
AB  - BACKGROUND: The objectives of this smoking cessation study among hospitalized
      smokers are to: 1) determine provider and patient receptivity, barriers, and
      facilitators to implementing the nurse-administered, inpatient Tobacco Tactics
      intervention versus usual care using face-to-face feedback and surveys; 2)
      compare the effectiveness of the nurse-administered, inpatient Tobacco Tactics
      intervention versus usual care across hospitals, units, and patient
      characteristics using thirty-day point prevalence abstinence at thirty days and
      six months (primary outcome) post-recruitment; and 3) determine the cost
      effectiveness of the nurse-administered, inpatient Tobacco Tactics intervention
      relative to usual care including cost per quitter, cost per life-year saved, and
      cost per quality-adjusted life-year saved. METHODS/DESIGN: This effectiveness
      study will be a quasi-experimental design of six Michigan community hospitals of
      which three will get the nurse-administered Tobacco Tactics intervention and
      three will provide their usual care. In both the intervention and usual care
      sites, research assistants will collect data from patients on their smoking
      habits and related variables while in the hospital and at thirty days and six
      months post-recruitment. The intervention will be integrated into the
      experimental sites by a research nurse who will train Master Trainers at each
      intervention site. The Master Trainers, in turn, will teach the intervention to
      all staff nurses. Research nurses will also conduct formative evaluation with
      nurses to identify barriers and facilitators to dissemination.Descriptive
      statistics will be used to summarize the results of surveys administered to
      nurses, nurses' participation rates, smokers' receipt of specific cessation
      services, and satisfaction with services. General estimating equation analyses
      will be used to determine differences between intervention groups on satisfaction
      and quit rates, respectively, with adjustment for the clustering of patients
      within hospital units. Regression analyses will test the moderation of the
      effects of the interventions by patient characteristics. Cost-effectiveness will
      be assessed by constructing three ratios including cost per quitter, cost per
      life-year saved, and cost per quality-adjusted life-year saved. DISCUSSION: Given
      that nurses represent the largest group of front-line providers, this
      intervention, if proven effective, has the potential for having a wide reach and
      thus decrease smoking, morbidity and mortality among inpatient smokers. TRIAL
      REGISTRATION: Dissemination of Tobacco Tactics for Hospitalized Smokers
      NCT01309217.

PMID- 22852835
TI  - The development of the Be Active & Relax "Vitality in Practice" (VIP) project and
      design of an RCT to reduce the need for recovery in office employees.
AB  - BACKGROUND: There is strong evidence to suggest that multiple work-related health
      problems are preceded by a higher need for recovery. Physical activity and
      relaxation are helpful in decreasing the need for recovery. This article aims to
      describe (1) the development and (2) the design of the evaluation of a daily
      physical activity and relaxation intervention to reduce the need for recovery in
      office employees. METHODS/DESIGN: The study population will consist of employees
      of a Dutch financial service provider. The intervention was systematically
      developed, based on parts of the Intervention Mapping (IM) protocol. Assessment
      of employees needs was done by combining results of face-to-face interviews, a
      questionnaire and focus group interviews. A set of theoretical methods and
      practical strategies were selected which resulted in an intervention program
      consisting of Group Motivational Interviewing (GMI) supported by a social media
      platform, and environmental modifications. The Be Active & Relax program will be
      evaluated in a modified 2 X 2 factorial design. The environmental modifications
      will be pre-stratified and GMI will be randomised on department level. The
      program will be evaluated, using 4 arms: (1) GMI and environmental modifications;
      (2) environmental modifications; (3) GMI; (4) no intervention (control group).
      Questionnaire data on the primary outcome (need for recovery) and secondary
      outcomes (daily physical activity, sedentary behaviour, relaxation/detachment,
      work- and health-related factors) will be gathered at baseline (T0), at 6 months
      (T1), and at 12 months (T2) follow-up. In addition, an economic and a process
      evaluation will be performed. DISCUSSION: Reducing the need for recovery is
      hypothesized to be beneficial for employees, employers and society. It is assumed
      that there will be a reduction in need for recovery after 6 months and 12 months
      in the intervention group, compared to the control group. Results are expected in
      2013. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2553.

PMID- 22852836
TI  - Chemical modification study of antisense gapmers.
AB  - A series of insertion patterns for chemically modified nucleotides [2'-O-methyl
      (2'-OMe), 2'-fluoro (2'-F), methoxyethyl (MOE), locked nucleic acid (LNA), and G
      Clamp] within antisense gapmers is studied in vitro and in vivo in the context of
      the glucocorticoid receptor. Correlation between lipid transfection and
      unassisted (gymnotic--using no transfection agent) in vitro assays is seen to be
      dependent on the chemical modification, with the in vivo results corresponding to
      the unassisted assay in vitro. While in vitro mRNA knockdown assays are typically
      reasonable predictors of in vivo results, G-Clamp modified antisense
      oligonucleotides have poor in vivo mRNA knockdown as compared to transfected cell
      based assays. For LNA gapmers, knockdown is seen to be highly sensitive to the
      length of the antisense and number of LNA insertions, with longer 5LNA-10DNA-5LNA
      compounds giving less activity than 3LNA-10DNA-3LNA derivatives. Additionally,
      the degree of hepatoxicity for antisense gapmers with identical sequences was
      seen to vary widely with only subtle changes in the chemical modification
      pattern. While the optimization of knockdown and hepatic effects remains a
      sequence specific exercise, general trends emerge around preferred physical
      properties and modification patterns.

PMID- 22852837
TI  - Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for
      urinary tract infection: assessment of protective effects in a rat model.
AB  - OBJECTIVE: To determine the protective effects of hyaluronic acid and chondroitin
      sulfate in treating urinary tract infections in a rat model. METHODS: A total of
      28 rats, which were induced with urinary tract infections through intravesical
      administration of Escherichia coli, were included in the study. By random
      selection, they were equally divided into four groups as control (no treatment),
      hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate.
      Bacteriological cultures of the urine and bladder tissue samples were carried
      out, and the data for each group were statistically compared. RESULTS: In the
      urine cultures, there were significant differences in median bacterial growth
      rates in hyaluronic acid (5 * 10(3) cfu/mL) and chondroitin sulfate (1 * 10(4)
      cfu/mL) groups relative to the control group (5 * 10(4) cfu/mL). However, a
      significantly lower rate of bacterial colony growth was observed in the
      hyaluronic acid + chondroitin sulfate group (8 * 10(2) cfu/mL; P < 0.05). In the
      bladder tissues, statistically significant decreases in median bacterial growth
      rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin
      sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium
      damage decreased in the treatment groups. However, this effect was prominent in
      hyaluronic acid + chondroitin sulfate group. CONCLUSION: Our experimental
      findings show that the hyaluronic acid + chondroitin sulfate combination has a
      potential benefit in reducing the bacterial load in urine and the thickness of
      the transitional epithelium.

PMID- 22852838
TI  - How healthcare professionals respond to parents with religious objections to
      vaccination: a qualitative study.
AB  - BACKGROUND: In recent years healthcare professionals have faced increasing
      concerns about the value of childhood vaccination and many find it difficult to
      deal with parents who object to vaccination. In general, healthcare professionals
      are advised to listen respectfully to the objections of parents, provide honest
      information, and attempt to correct any misperceptions regarding vaccination.
      Religious objections are one of the possible reasons for refusing vaccination.
      Although religious objections have a long history, little is known about the way
      healthcare professionals deal with these specific objections. The aim of this
      study is to gain insight into the responding of healthcare professionals to
      parents with religious objections to the vaccination of their children. METHODS:
      A qualitative interview study was conducted with health care professionals (HCPs)
      in the Netherlands who had ample experience with religious objections to
      vaccination. Purposeful sampling was applied in order to include HCPs with
      different professional and religious backgrounds. Data saturation was reached
      after 22 interviews, with 7 child health clinic doctors, 5 child health clinic
      nurses and 10 general practitioners. The interviews were thematically analyzed.
      Two analysts coded, reviewed, discussed, and refined the coding of the
      transcripts until consensus was reached. Emerging concepts were assessed using
      the constant comparative method from grounded theory. RESULTS: Three manners of
      responding to religious objections to vaccination were identified: providing
      medical information, discussion of the decision-making process, and adoption of
      an authoritarian stance. All of the HCPs provided the parents with medical
      information. In addition, some HCPs discussed the decision-making process. They
      verified how the decision was made and if possible consequences were realized.
      Sometimes they also discussed religious considerations. Whether the decision
      making process was discussed depended on the willingness of the parents to engage
      in such a discussion and on the religious background, attitudes, and
      communication skills of the HCPs. Only in cases of tetanus post-exposure
      prophylaxis, general practitioners reported adoption of an authoritarian stance.
      CONCLUSION: Given that the provision of medical information is generally not
      decisive for parents with religious objections to vaccination, we recommend HCPs
      to discuss the vaccination decision-making process, rather than to provide them
      with extra medical information.

PMID- 22852839
TI  - Bioaccessibility of uranium in soil samples from Port Hope, Ontario, Canada.
AB  - Adequate assessment of human health risk of uranium contamination at hazardous
      waste sites, which is an important step in determining the cleanup strategy, is
      based on bioavailability data. Bioavailability of uranium from contaminated soil
      has not been properly determined yet. Bioaccessibility is an in vitro
      conservative estimate of bioavailability and is thus frequently used for site
      specific risk assessment. Bioaccessibility of uranium was measured in 33 soil
      samples from the Port Hope area in Ontario, Canada, by the physiologically based
      extraction test (PBET). Higher bioaccessibility values in the gastric plus
      intestinal phase, 48.4% +/- 16.8%, than in the gastric phase, 20.8% +/- 11.7%,
      are very probably the result of more efficient extraction of uranium from soil by
      intestinal fluid rich in carbonate ions. The observed variability of measured
      bioaccessibility values is discussed in light of the results of scanning electron
      microscope examination of the soil samples. Uranium bioaccessibility values in
      both gastric (acidic) and gastric plus intestinal (neutral) phases are higher in
      soil samples with smaller uranium-bearing particles and lower in samples where
      the uranium-bearing particles are larger. We postulate that the most important
      reason for variability of measured bioaccessibility values in Port Hope soil
      samples may be the difference in particle size of uranium-bearing particles.

PMID- 22852840
TI  - Flexible and efficient eletrokinetic stacking of DNA and proteins at an HF etched
      porous junction on a fused silica capillary.
AB  - Better understanding of the mechanism is important for exploring the potentials
      of a preconcentration method. In this work, we show for the first time that the
      HF etched porous junction on a fused silica capillary behaves not only as a
      filter but also as an integrated nanofluidic interface. This junction exhibits an
      obvious ion concentration polarization (CP) effect, with which highly efficient
      electrokinetic stacking (ES) inside the capillary can be achieved without
      molecular size or charge type limitation. Two major types of CP based ES were
      proposed, and an autostop etching principle was presented for avoiding
      overetching. The ES can be performed in a broad range of pH and buffer
      concentration. Over a billion times of concentration was demonstrated by a
      fluorescein probe with laser induced fluorescent (LIF) detection. ES of
      fluorescently labeled and native DNA and protein were characterized by charge
      coupled device (CCD) imaging and online capillary gel electrophoresis (CGE) with
      ultraviolet (UV) absorption detections, respectively. With this junction, highly
      efficient ES can be performed easily by voltage manipulation without any
      mechanical operation. We may foresee that the performance of capillary-based
      conventional and chip electrophoresis could be greatly enhanced with this
      junction in the analysis of low abundance biomolecules.

PMID- 22852841
TI  - Unique proline-benzoquinone pigment from the colored nectar of "bird's Coca cola
      tree" functions in bird attractions.
AB  - The major pigment responsible for the dark brown nectar of the "bird's Coca cola
      tree", Leucosceptrum canum (Labiatae), was isolated and identified as a unique
      symmetric proline-quinone conjugate, 2,5-di-(N-(-)-prolyl)-para-benzoquinone
      (DPBQ). Behavioral experiments with both isolated and synthetic authentic samples
      indicated that DPBQ functions mainly as a color attractant to bird pollinators.

PMID- 22852842
TI  - Epidermal growth factor 61A>G polymorphism is associated with risk of
      hepatocellular carcinoma: a meta-analysis.
AB  - The association between hepatocellular carcinoma (HCC) and the 61A>G polymorphism
      in the epidermal growth factor (EGF) gene has been analyzed in several studies,
      but results have been inconsistent. The aim of this study was to integrate
      previous findings and explore whether this polymorphism is associated with
      susceptibility to HCC. A meta-analysis was performed by searching PubMed, Web of
      Science, and Cochrane Library databases. Data were extracted using predefined
      form and pooled odds ratios (OR) with 95% confidence intervals (CI) and were
      calculated to evaluate the strength of this association. Five studies involving
      690 cases, 514 healthy controls, and 1419 controls with cancer-free liver
      diseases were identified. On the basis of healthy controls, the significant main
      effects on HCC risk were observed in a heterozygote comparison (OR=1.76, 95% CI
      1.07-2.90, p=0.02) and a dominant genetic model (OR=1.65, 95% CI 1.03-2.66,
      p=0.04). On the basis of the controls with cancer-free liver diseases, a
      significantly increased risk of HCC was found in all the genetic models. Subgroup
      analyses stratified by ethnicity and etiology of HCC also showed positive
      associations. The EGF 61G allele is a risk factor for developing HCC without the
      influence of ethnic and etiological diversity.

PMID- 22852843
TI  - Quantification of the typical weekly in-season training load in elite junior
      soccer players.
AB  - We examined the typical weekly training load experienced by elite junior soccer
      players during the in-season competitive period. Altogether, eight under-14
      (U14), eight under-16 (U16) and eight under-18 (U18) players were monitored over
      a 2-week period during the first month of the 2010-11 competitive season. This
      time period included one competitive match per week. Physiological loading was
      monitored using heart rate (HR) and ratings of perceived exertion (RPE). Training
      and match loads were calculated by multiplying the global session RPE and
      duration (session-RPE). Total weekly training load (training and match) increased
      with age (U14, 2524 +/- 128 arbitrary units [AU]; U16, 2919 +/- 136 AU; U18, 3948
      +/- 222 AU; P < 0.05). Differences in the daily training load across the training
      week were also evident in the older age group relative to both U14 and U16. The
      amount of time engaged in low (<50% HRmax) and high (>90% HRmax) intensity
      activity during training and match-play was significantly lower and higher
      respectively in the U18 compared to the U14 group (P < 0.05). When comparing
      activity, the intensity (% HRmax) of field training (U18, 69 +/- 2%; U16, 74 +/-
      1%; U14, 74 +/- 2%) was significantly lower compared to match-play (U18, 81 +/-
      3%; U16, 84, +/- 2%; U14, 83 +/- 2) across all age groups (P < 0.05). Findings
      demonstrate that age related differences in the volume and intensity of weekly in
      season training load are evident amongst elite professional junior soccer
      players. These differences may reflect a systematic approach to the long-term
      physical development of elite junior players.

PMID- 22852845
TI  - Tributyltin impairs the coronary vasodilation induced by 17beta-estradiol in
      isolated rat heart.
AB  - Triorganotins, such as tributyltin (TBT), are environmental contaminants that are
      commonly used as antifouling agents for boats. However, TBT is also known to
      alter mammalian reproductive functions. Although the female sex hormones are
      primarily involved in the regulation of reproductive functions, 17beta-estradiol
      also protects against cardiovascular diseases, in that this hormone reduces the
      incidence of coronary artery disease via coronary vasodilation. The aim of this
      study was to examine the influence of 100 ng/kg TBT administered daily by oral
      gavage for 15 d on coronary functions in female Wistar rats. Findings were
      correlated with changes in sex steroids concentrations. Tributyltin significantly
      increased the baseline coronary perfusion pressure and impaired vasodilation
      induced by 17beta-estradiol. In addition, TBT markedly decreased serum 17beta
      estradiol levels accompanied by a significant rise in serum progesterone levels.
      Tributyltin elevated collagen deposition in the heart interstitium and number of
      mast cells proximate to the cardiac vessels. There was a positive correlation
      between the increase in coronary perfusion pressure and incidence of cardiac
      hypertrophy. In addition, TBT induced endothelium denudation (scanning electron
      microscopy) and accumulation of platelets. Moreover, TBT impaired coronary
      vascular reactivity to estradiol (at least in part), resulting in endothelial
      denudation, enhanced collagen deposition and elevated number of mast cells. Taken
      together, the present results demonstrate that TBT exposure may be a potential
      risk factor for cardiovascular disorders in rats.

PMID- 22852846
TI  - Evaluation of glutathione S-transferase GSTM1 and GSTT1 polymorphisms and
      methylmercury metabolism in an exposed Amazon population.
AB  - Over the last decades, the presence of methylmercury (MeHg) in the Amazon region
      of Brazil and its adverse human health effects have given rise to much concern.
      The biotransformation of MeHg occurs mainly through glutathione (GSH) in the bile
      mediated by conjugation with glutathione S-transferases (GST). Epidemiological
      evidence has shown that genetic polymorphisms may affect the metabolism of MeHg.
      The aim of this study was to evaluate the association between GST polymorphisms,
      GSH, and Hg levels in blood (B-Hg) and in hair (H-Hg) of an Amazon population
      chronically exposed to the metal through fish consumption. Blood and hair samples
      were collected from 144 volunteers (71 men, 73 women). B-Hg and H-Hg levels were
      determined by inductively coupled plasma-mass spectrometry, and GSH levels were
      evaluated by a spectrophotometric method. GSTM1 and T1 genotyping evaluation were
      carried out by multiplex polymerase chain reaction (PCR). Mean levels of B-Hg and
      H-Hg were 37.7 +/- 24.5 MUg/L and 10.4 +/- 7.4 MUg/g, respectively; GSH
      concentrations ranged from 0.52 to 2.89 MUM/ml of total blood. Distributions for
      GSTM1/T1, GSTM1/GSTT1*0, GSTM1*0/T1, and GSTM1*0/GSTT1*0 genotypes were 35.4,
      22.2, 25.0, and 17.4%, respectively. GSTT1 genotype carriers presented lower
      levels of B-Hg and H-Hg when compared to other genotypes carriers. In addition,
      GSTM1*0/GSTT1*0 individuals presented higher Hg levels in blood and hair than
      subjects presenting any other genotypes. There appeared to be no evidence of an
      effect of polymorphisms on GSH levels. Therefore, our data suggest that GST
      polymorphisms may be associated with MeHg detoxification.

PMID- 22852847
TI  - Environmental tobacco smoke induces oxidative stress in distinct brain regions of
      infant mice.
AB  - Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers
      annually and is associated with disturbances in antioxidant enzyme capacity in
      the adult rodent brain. However, little is known regarding the influence of ETS
      on brain development. The aim of this study was to determine levels of
      malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant
      activities of glutathione peroxidase (GPx), glutathione reductase (GR),
      glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct
      brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from
      postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on
      postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the
      last exposure. Immediately after an acute exposure there were higher GR and GST
      activities and MDA levels in the hippocampus, higher GPx and SOD activities in
      the prefrontal cortex, and higher GST activity and MDA levels in the striatum and
      cerebellum. Three hours later there was an increase in SOD activity and MDA
      levels in the hippocampus and a decrease in the activity of all enzymes in the
      prefrontal cortex. Immediately after final repeated exposure there were elevated
      levels of GST and GR activity and decreased GPx activity in the hippocampus.
      Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and
      increased GST and GPx activity in the striatum and cerebellum, respectively.
      After 3 h the prefrontal cortex showed elevated GR and GST activities, and the
      striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant
      system in the central nervous system responds to ETS differently in different
      regions of the brain and that a form of adaptation occurs after several days of
      exposure.

PMID- 22852849
TI  - Hepatotoxicity assessment of the azo dyes disperse orange 1 (DO1), disperse red 1
      (DR1) and disperse red 13 (DR13) in HEPG2 cells.
AB  - During the dyeing process in baths approximately 10 to 15% of the dyes used are
      lost and reach industrial effluents, thus polluting the environment. Studies
      showed that some classes of dyes, mainly azo dyes and their by-products, exert
      adverse effects on humans and local biota, since the wastewater treatment systems
      and water treatment plants were found to be ineffective in removing the color and
      reducing toxicity of some dyes. In the present study, the toxicity of the azo
      dyes disperse orange 1 (DO1), disperse red 1 (DR1), and disperse red 13 (DR13)
      was evaluated in HepG2 cells grown in monolayers or in three dimensional (3D)
      culture. Hepatotoxicity of the dyes was measured using 3-(4,5-dimethylthiazol
      2yl)2,5-diphenyltetrazolium (MTT) and cell counting kit 8 (CCK-8) assays after
      24, 48, and 72 h of incubation of cells with 3 different concentrations of the
      azo dyes. The dye DO1 only reduced the mitochondrial activity in HepG2 cells
      grown in a monolayer after 72 h incubation, while the dye DR1 showed this
      deleterious effect in both monolayer and 3D culture. In contrast, dye DR13
      decreased the mitochondrial activity after 24, 48, and 72 h of exposure in both
      monolayer and 3D culture. With respect to dehydrogenase activity, only the dye
      DR13 diminished the activity of this enzyme after 72 h of exposure in both
      monolayer and 3D culture. Our results clearly demonstrated that exposure to the
      studied dyes induced cytotoxicity in HepG2 cells.

PMID- 22852848
TI  - Carvedilol protects against apoptotic cell death induced by cisplatin in renal
      tubular epithelial cells.
AB  - Cisplatin is a highly effective chemotherapeutic drug; however, its use is
      limited by nephrotoxicity. Studies showed that the renal injury produced by
      cisplatin involves oxidative stress and cell death mediated by apoptosis and
      necrosis in proximal tubular cells. The use of antioxidants to decrease cisplatin
      induced renal cell death was suggested as a potential therapeutic measure. In
      this study the possible protective effects of carvedilol, a beta blocker with
      antioxidant activity, was examined against cisplatin-induced apoptosis in HK-2
      human kidney proximal tubular cells. The mitochondrial events involved in this
      protection were also investigated. Four groups were used: controls (C), cisplatin
      alone at 25 MUM (CIS), cisplatin 25 MUM plus carvedilol 50 MUM (CV + CIS), and
      carvedilol alone 50 MUM (CV). Cell viability, apoptosis, caspase-9, and caspase-3
      were determined. Data demonstrated that carvedilol effectively increased cell
      viability and minimized caspase activation and apoptosis in HK-2 cells,
      indicating this may be a promising drug to reduce nephrotoxicity induced by
      cisplatin.

PMID- 22852850
TI  - Evaluation of the mutagenic activity of chrysin, a flavonoid inhibitor of the
      aromatization process.
AB  - Chrysin is one of the natural flavonoids present in plants, and large amounts are
      present in honey and propolis. In addition to anticancer, antioxidation, and anti
      inflammatory activities, chrysin has also been reported to be an inhibitor of
      aromatase, an enzyme converting testosterone into estrogen. The present study
      evaluated the mutagenicity of this flavonoid using micronucleus (MN) with HepG2
      cells and Salmonella. Cell survival after exposure to different concentrations of
      chrysin was also determined using sulforhodamine B (SRB) colorimetric assay in
      HepG2 cells and the influence of this flavonoid on growth of cells in relation to
      the cell cycle and apoptosis. The MN test showed that from 1 to 15 MUM of this
      flavonoid mutagenic activity was noted in HepG2 cells. The Salmonella assay
      demonstrated a positive response to the TA100 Salmonella strain in the presence
      or absence of S9, suggesting that this compound acted on DNA, inducing base pair
      substitution before or after metabolism via cytochrome P-450. The SRB assay
      illustrated that chrysin promoted growth inhibition of HepG2 cells in both
      periods studied (24 and 48 h). After 24 h of exposure it was noted that the most
      significant results were obtained with a concentration of 50 MUM, resulting in
      83% inhibition and SubG0 percentage of 12%. After 48 h of incubation cell
      proliferation inhibition rates (97% at 50 MUM) were significantly higher. Our
      results showed that chrysin is a mutagenic and cytotoxic compound in cultured
      human HepG2 cells and Salmonella typhimurium. Although it is widely accepted that
      flavonoids are substances beneficial to health, one must evaluate the risk versus
      benefit relationship and concentrations of these substances to which an
      individual may be exposed.

PMID- 22852851
TI  - Molecular docking studies of disubstituted diaryl diselenides as mammalian delta
      aminolevulinic acid dehydratase enzyme inhibitors.
AB  - delta-Aminolevulinic acid dehydratase (delta-ALAD) is a metalloprotein that
      catalyzes porphobilinogen formation. This enzyme is sensitive to pro-oxidants and
      classically used as a biomarker of lead (Pb) intoxication. Diphenyl diselenide
      [(PhSe)2] and analogs bis(4-chlorophenyl) diselenide [(pCl3PhSe)2], bis(4
      methoxyphenyl)diselenide [(pCH3OPhSe)2], and bis[3-(trifluoromethy)phenyl]
      diselenide [(mCF3PhSe)2] inhibit mammalian delta-ALAD by oxidizing enzyme
      cysteinyl residues, which are involved in diselenide-induced toxicity. 2
      Cysteinyl residues from delta-ALAD are believed to sequentially interact with
      (PhSe)2. Thus this study utilized protein-ligand docking analyses to determine
      which cysteinyl residues might be involved in the inhibitory effect of (PhSe)2
      and analogs toward delta-ALAD. All diselenides that interact in a similar manner
      with the active site of delta-ALAD were examined. Docking simulations indicated
      an important role for pi-pi interactions involving Phe208 and cation-pi
      interactions involving Lys199 and Arg209 residues with the aromatic ring of
      (PhSe)2 and analogs. Based upon these interactions an approximation between Se
      atoms and -SH of Cys124, with distances ranging between 3.3 A and 3.5 A, was
      obtained. These data support our previous postulations regarding the mechanism
      underlying delta-ALAD oxidation mediated by (PhSe)2 and analogs. Based on protein
      ligand docking analyses, data indicated that -SH of Cys124 attacks one of the Se
      atoms of -SH of (PhSe)2 releasing one PhSeH (selenophenol). Subsequently, the -SH
      of Cys132 attacks the sulfur atom of Cys124 (from the bond of E-S-Se-Ph
      indermediate), generating the second PhSe-, and the oxidized and inhibited delta
      ALAD. In conclusion, AutoDock Vina 1.1.1 was a useful tool to search for
      diselenides inhibitors of delta-ALAD, and, most importantly, it provided insight
      into molecular mechanisms involved in enzyme inhibition.

PMID- 22852853
TI  - Tributyltin impairs the reproductive cycle in female rats.
AB  - Triorganotins are environmental contaminants, commonly used in antifouling agents
      for boats, that bioaccumulate and thus are found in mammals and humans due to
      ingestion of contaminated seafood diets. The importance of triorganotins as
      environmental endocrine disruptors and consequent reproductive toxicity in
      different animal models is well known; however, the adverse effects on
      reproductive cycle are less well understood. The potential reproductive toxicity
      of tributyltin (TBT) on regular reproductive cycling of female rats was examined.
      Wistar female rats (12 wk old, weighing approximately 230 g) were divided into
      two groups: control (vehicle, ethanol 0.4%) and tributyltin (100 ng/kg/d, 7 d/wk,
      for 16 d by gavage). Tributyltin significantly decreased the cycle regularity
      (%), duration of the reproductive cycle, the proestrus and diestrus phases, and
      number of epithelial cell in proestrus phase. TBT also increased the duration of
      metestrus and the number of cornified cells in this phase. Ovary weight and serum
      17beta-estradiol levels decreased markedly, accompanied by a significant increase
      in progesterone levels. Histological analysis showed apoptotic cells in corpus
      luteum and granulosa cells layer, with cystic follicles after TBT exposure.
      Tributyltin also elevated number of atretic follicles and corpoa lutea. The
      micronucleus (MN) test, using Chinese hamster ovary cells, demonstrated a
      concentration-dependent mutagenic effect of TBT, and at 2.0 * 10(-2)ng/ml most of
      the cells were nonviable. The toxic potential of TBT over the reproductive cycle
      may be attributed to changes found in the ovarian weight, unbalanced levels of
      sexual female hormones, and number of ovarian follicles and corpora lutea.

PMID- 22852852
TI  - Biomarkers of organic contamination in the South American fish Poecilia vivipara
      and Jenynsia multidentata.
AB  - South American cyprinodontiform fish are potential candidates to be used as model
      biomarker species of exposure in environmental toxicology. The aim of this study
      was to identify molecular and biochemical biomarkers of pollution using Poecilia
      vivipara (Poecilidae) and Jenynsia multidentata (Anablepidae). Partial nucleotide
      sequences for cytochrome P-450 1A (CYP1A), a classical biomarker of exposure to
      organic contaminants in fish, were identified in P. vivipara and J. multidentata
      (approximately 650 nucleotides) using degenerated primers and polymerase chain
      reaction (PCR). These sequences shared approximately 90% identity in the
      predicted amino acid sequence with the corresponding CYP1A region of Fundulus
      heteroclitus. Real-time quantitative PCR (RT-qPCR) analysis confirmed that CYP1A
      transcription was markedly induced in the liver and gills of J. multidentata
      (approximately185-fold and 20-fold, respectively) and P. vivipara (122-fold and
      739-fold, respectively) 24 h after exposure to 1 MUM synthetic CYP1A inducer beta
      naphthoflavone (BNF). At 24 h after injection with 1 MUg/g environmental
      carcinogenic contaminant benzo[a]pyrene (BaP), a decreased total antioxidant
      capacity against peroxyl radicals was observed both in liver of J. multidentata
      and gills of P. vivipara. BaP injection in both fish did not produce changes in
      lipid peroxide (thiobarbituric acid-reactive substances, TBARS) levels,
      suggesting an absence of an oxidative stress condition. The newly identified
      CYP1A may thus serve as general biomarker of exposure to organic contaminant in
      future studies using P. vivipara and J. multidentata. Data also indicate the
      importance of species-specific differences in biomarker responses in these South
      American cyprinodontiform fish, suggesting distinct resistance/susceptibility
      properties to polycyclic aromatic hydrocarbons.

PMID- 22852854
TI  - Sperm quality in adult male rats exposed to cadmium in utero and lactation.
AB  - Recent studies indicate that several anomalies of the male reproductive system
      may be produced by acute or chronic exposure to chemical substances released into
      the environment, attributed to increased industrial development. Among these
      substances are trace metals such as cadmium (Cd). The aim of this study was to
      assess reproductive parameters in adult male rats whose mothers were exposed to
      Cd during pregnancy and lactation. For this, pregnant rats were divided into two
      experimental groups: treated rats, which received ad libitum cadmium acetate
      (CdAc) solution in distilled water (10 mg Cd/L), and control rats, which received
      sodium acetate (NaAc) solution in distilled water (equimolar to the CdAc). The
      results showed that the exposure to Cd in utero and through lactation adversely
      affected sperm quality of adult rats, as evidenced by compromised sperm
      morphology and motility and increased rate of cell death in testis.

PMID- 22852856
TI  - Microbiological evaluation of different strategies for management of snakes in
      captivity.
AB  - Keeping snakes in captivity to produce venom for scientific research and
      production of inputs is now a worldwide practice. Maintaining snakes in captivity
      involves capture, infrastructure investments, management techniques, and
      appropriate qualified personnel. Further, the success of the project requires
      knowledge of habitat, nutrition, and reproduction, and control of opportunistic
      infections. This study evaluated the management of snakes in three types of
      captivity (quarantine, intensive, and semiextensive) and diagnosed bacterial and
      fungal contaminants. A bacteriological profile was obtained by swabbing the oral
      and cloacal cavities, scales, and venoms of healthy adult snakes from Bothrops
      jararaca (Bj) and Crotalus durissus terrificus (Cdt). There was predominance of
      Enterobacteriaceae, especially non-fermenting Gram-negative bacilli excluding
      Pseudomonas spp and Gram- positive bacteria. Statistically, intensive captivity
      resulted in the highest number of bacterial isolates, followed by recent capture
      (quarantine) and by semiextensive captivity. No statistical difference was found
      between Bj and Cdt bacterial frequency. In vitro bacterial susceptibility testing
      found the highest resistance against the semisynthetic penicillins (amoxicillin
      and ampicillin) and highest sensitivity to amicacin and tobramycin
      aminoglycosides. To evaluate mycological profile of snakes from intensive
      captivity, samples were obtained from two healthy Bj and one B. moojeni, one B.
      pauloensis, and one Cdt showing whitish lesions on the scales suggestive of
      ringworm. Using conventional methods and DNA-based molecular procedures, five
      samples of Trichosporon asahii were identified. Despite the traditional role of
      intense captivity in ophidian venom production, semiextensive captivity was more
      effective in the present study by virtue of presenting superior control of
      bacterial and fungal transmission, easier management, lowest cost, and decreased
      rate of mortality; therefore, it should be considered as a good alternative for
      tropical countries.

PMID- 22852855
TI  - Effects of diuron on male rat reproductive organs: a developmental and postnatal
      study.
AB  - This study was performed to determine whether developmental exposure (perinatal
      and juvenile) to the herbicide diuron exerted adverse effects on adult rat male
      reproductive system. Pregnant Sprague-Dawley rats received basal diet or diet
      containing diuron at 500 or 750 ppm from gestational day 12 (GD 12) until the end
      of lactation period (postnatal day 21, PND 21). After weaning male offspring
      received basal diet or diet containing diuron until PND 42 (peripubertal age). At
      PND 90, adult male rats from each experimental group were anesthetized and
      euthanized for evaluation of body and reproductive organ weights, sperm
      parameters, plasma testosterone levels, and testicular and epididymal
      histopathology. Male offspring exposed to diuron at 750 ppm displayed reduced
      body weight at PND 10, 21, 42, and 90 compared to controls. At PND 90, diuron
      treatment did not induce significant change in daily sperm production, sperm
      morphology and motility, and testosterone levels compared to controls. In
      conclusion, diuron at 750 ppm induced male offspring toxicity but these
      alterations were not permanent, as evidenced by absence of reproductive-system
      alterations in adult Sprague Dawley rats.

PMID- 22852857
TI  - Intraspecific variation of biological activities in venoms from wild and captive
      Bothrops jararaca.
AB  - The venom of Bothrops jararaca is composed of complex mixture of molecules,
      mainly lectins, metalloproteinases, serinoproteinases, desintegrins,
      phospholipases, and peptides. This composition may vary according to the snake's
      age, gender, and region of origin. The aim of the was to determine individual
      variation in Bothrops jararaca venom in the Botucatu region, Sao Paulo State,
      Brazil, by means of enzymatic, biochemical, and pharmacological characterization,
      utilizing in vitro tests and biological assays. The activities were compared with
      those of Brazilian Reference Venom (BRV). Protein concentration varied between
      adult and juvenile groups. The electrophoretic profiles were similar, with
      molecular masses ranging between 25 and 50 kD, but with intraspecific variations.
      Reverse-phase high-performance liquid chromatography (RP-HPLC) revealed protein
      concentration differences. Coagulant activity did not differ significantly among
      adult groups, but there was a large variation between juvenile venom and BRV,
      which coagulated more extensively. Venoms from adults displayed greater
      hemorrhagic activity, especially in males recently obtained from the wild. In
      contrast, juveniles kept in captivity and adult males showed higher values.
      Edematogenic activity displayed an increase in edema in all groups. At the mean
      lethal dose (LD50), toxicity varied significantly between groups, with venom from
      captive females being threefold more toxic than juvenile venom. Data illustrate
      the intra- and interspecific complexity that occurs in snake venoms, which may be
      attributed to ontogenetic, sexual, and environmental factors that affect
      variability in Bothrops jararaca venom. Further, it is proposed that Brazilian
      public health authorities document the constitution of pooled venom employed in
      the immunization of serum-producing animals due to this variability in venom
      properties. Given the large Brazilian territory, this variability requires
      regional monitoring and evaluation of the efficacy of bothropic antivenom in
      treatment of snakebite and consequent permanent sequelae observed.

PMID- 22852858
TI  - Glia and methylmercury neurotoxicity.
AB  - Methylmercury (MeHg) is a global environmental pollutant with significant adverse
      effects on human health. As the major target of MeHg, the central nervous system
      (CNS) exhibits the most recognizable poisoning symptoms. The role of the two
      major nonneuronal cell types, astrocytes and microglia, in response to MeHg
      exposure was recently compared. These two cell types share several common
      features in MeHg toxicity, but interestingly, these cells types also exhibit
      distinct response kinetics, indicating a cell-specific role in mediating MeHg
      induced neurotoxicity. The aim of this study was to review the most recent
      literature and summarize key features of glial responses to this organometal.

PMID- 22852859
TI  - Mikania glomerata Sprengel (Asteraceae) influences the mutagenicity induced by
      doxorubicin without altering liver lipid peroxidation or antioxidant levels.
AB  - As shown in numerous studies, natural compounds may exert adverse effects, mainly
      when associated with some drugs. The hydroalcoholic extract of Mikania glomerata
      is the pharmaceutical form present in commercially available syrup used for the
      treatment of respiratory diseases in popular Brazilian medicine. The objective of
      the present investigation was (1) to evaluate the preventive effects of
      standardized hydroalcoholic extract of M. glomerata (MEx) against antitumoral
      drug doxorubicin (DXR)-induced micronucleated polychromatic erythrocytes (MNPCE)
      in a subchronic assay in mice, and (2) to determine the liver content of
      malondialdehyde (MDA) and the antioxidants glutathione (GSH) and vitamin E (VE).
      Male Swiss mice were treated for 30 d with MEx added to drinking water, combined
      or not with DXR (90 mg/kg body weight) injected intraperitoneally (ip) 24 h
      before analysis. The results demonstrated that MEx produced no genotoxic damage,
      but significantly increased the frequency of MNPCE induced by DXR, indicating a
      drug-drug interaction. This rise was not accompanied by lipid peroxidation or
      antioxidants level reduction, as measured by MDA, GSH, and VE. Despite the
      presence of coumarin (a known antioxidant), MEx may exert adverse effects
      probably in association with mutagenic compounds, although this effect on DNA
      damage did not involve oxidative stress.

PMID- 22852861
TI  - Revision of singlet quantum yields in the catalyzed decomposition of cyclic
      peroxides.
AB  - The chemiluminescence of cyclic peroxides activated by oxidizable fluorescent
      dyes is an example of chemically initiated electron exchange luminescence
      (CIEEL), which has been used also to explain the efficient bioluminescence of
      fireflies. Diphenoyl peroxide and dimethyl-1,2-dioxetanone were used as model
      compounds for the development of this CIEEL mechanism. However, the
      chemiexcitation efficiency of diphenoyl peroxide was found to be much lower than
      originally described. In this work, we redetermine the chemiexcitation quantum
      efficiency of dimethyl-1,2-dioxetanone, a more adequate model for firefly
      bioluminescence, and found a singlet quantum yield (Phi(S)) of 0.1%, a value at
      least 2 orders of magnitude lower than previously reported. Furthermore, we
      synthesized two other 1,2-dioxetanone derivatives and confirm the low
      chemiexcitation efficiency (Phi(S) < 0.1%) of the intermolecular CIEEL-activated
      decomposition of this class of cyclic peroxides. These results are compared with
      other chemiluminescent reactions, supporting the general trend that
      intermolecular CIEEL systems are much less efficient in generating singlet
      excited states than analogous intramolecular processes (Phi(S) ~ 50%), with the
      notable exception of the peroxyoxalate reaction (Phi(S) ~ 60%).

PMID- 22852860
TI  - Low modulus biomimetic microgel particles with high loading of hemoglobin.
AB  - We synthesized extremely deformable red blood cell-like microgel particles and
      loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With
      similar shape and size as red blood cells (RBCs), the particles were fabricated
      using the PRINT (particle replication in nonwetting templates) technique. Low
      cross-linking of the hydrogel resulted in very low mesh density for these
      particles, allowing passive diffusion of hemoglobin throughout the particles. Hb
      was secured in the particles through covalent conjugation of the lysine groups of
      Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy
      of particles bound to fluorescent dye-labeled Hb confirmed the uniform
      distribution of Hb throughout the particle interior, as opposed to the surface
      conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer
      by weight, were obtained without a significant effect on particle stability and
      shape, though particle diameter decreased slightly with Hb conjugation. Analysis
      of the protein by circular dichroism (CD) spectroscopy showed that the secondary
      structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in
      the particles could be maintained at a low level and the loaded Hb could still
      bind oxygen, as studied by UV-vis spectroscopy. Hb-loaded particles with moderate
      loading ratios demonstrated excellent deformability in microfluidic devices,
      easily deforming to pass through restricted pores half as wide as the diameter of
      the particles. The suspension of concentrated particles with a Hb concentration
      of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles
      remained intact even after being sheared at a constant high rate (1000 1/s) for
      10 min. Armed with the ability to control size, shape, deformability, and loading
      of Hb into RBC mimics, we will discuss the implications for artificial blood.

PMID- 22852863
TI  - Bax expression measured by AQUAnalysis is an independent prognostic marker in
      oral squamous cell carcinoma.
AB  - BACKGROUND: Resistance to apoptosis is a hallmark of cancer and proteins
      regulating apoptosis have been proposed as prognostic markers in several
      malignancies. However, the prognostic impact of apoptotic markers has not been
      consistently demonstrated in oral squamous cell carcinoma (OSCC). This
      inconsistency in reported associations between apoptotic proteins and prognosis
      can be partly attributed to the intrinsic low resolution and misclassification
      associated with manual, semi-quantitative methods of biomarker expression
      measurement. The aim of this study was to examine the association between
      apoptosis-regulating proteins and clinical outcomes in oral squamous cell
      carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC)
      based AQUAnalysis technique. METHODS: Sixty-nine OSCC patients diagnosed between
      1998-2005 in Calgary, Alberta, Canada were included in the study. Clinical data
      were obtained from the Alberta Cancer Registry and chart review. Tissue
      microarrays (TMAs) were assembled from triplicate cores of formalin-fixed
      paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein
      expression was quantified using fluorescent IHC and AQUA technology in normal
      oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was
      analyzed using Kaplan-Meier plots and the Cox proportional hazard model. RESULTS:
      Bax expression was predominantly nuclear in OCSE and almost exclusively
      cytoplasmic in OSCC. No similar differences in localization were observed for Bcl
      2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS),
      with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p
      = 0.006), in univariate analysis. High Bax expression was also significantly
      associated with elevated Ki67 expression, indicating that increased proliferation
      might lead to an improved response to radiotherapy in patients with elevated Bax
      expression. In multivariate analyses, Bax protein expression remained an
      independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013].
      CONCLUSIONS: The AQUA technique used in our study eliminates observer bias and
      provides reliable and reproducible estimates for biomarker expression. AQUA also
      provides essential measures of quality control that cannot be achieved with
      manual biomarker scoring techniques. Our results support the use of Bax protein
      expression as a prognostic marker in conjunction with other clinico-pathological
      variables when designing personalized treatment strategies for OSCC patients.

PMID- 22852864
TI  - Systematic review of randomized controlled trials to regulate glycaemia after
      stroke.
AB  - AIM: This article presents the results of a systematic review of randomized
      controlled trials on the regulation of glycaemia among adults admitted to
      hospital with acute stroke. BACKGROUND: Hyperglycaemia is commonly observed in
      acute stroke. International stroke guidelines recommend that hyperglycaemia is
      treated after stroke. Nurses have a key role in the monitoring and management of
      glycaemia. DESIGN: Systematic review. DATA SOURCES: A search for randomized
      controlled trials was conducted in MEDLINE and PubMed electronic databases, and
      original papers published between January 1996-June 2011 were identified. The
      search was performed using the terms 'stroke', 'hyperglycaemia', and 'treatment'
      combined. Searching of citations from identified studies was also used to
      supplement electronic searches. The search was limited to adults and English
      language publications. REVIEW METHODS: A systematic review was conducted for
      eight studies, meeting the inclusion criteria that: (i) insulin protocols were
      subjected to randomized controlled trial; and that (ii) only adults admitted to
      hospital with acute stroke were sampled. The review adheres to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis reporting standards.
      RESULTS: Intensive insulin therapy regimes have been investigated in a total of
      eight trials. Intravenous insulin therapy significantly lowers glucose levels
      when compared with controls but adherence to glucose monitoring and treatment
      protocols appeared to pose considerable challenge on nurses in routine stroke
      care. Trials conducted to date have been on poor to sound quality. CONCLUSION:
      There is currently no substantive evidence to support aggressive glucose lowering
      in the acute phase of stroke. Well-conducted, large randomized controlled trials
      are required.

PMID- 22852862
TI  - Direct simulation of early-stage Sec-facilitated protein translocation.
AB  - Direct simulations reveal key mechanistic features of early-stage protein
      translocation and membrane integration via the Sec-translocon channel. We present
      a novel computational protocol that combines non-equilibrium growth of the
      nascent protein with microsecond timescale molecular dynamics trajectories.
      Analysis of multiple, long timescale simulations elucidates molecular features of
      protein insertion into the translocon, including signal-peptide docking at the
      translocon lateral gate (LG), large lengthscale conformational rearrangement of
      the translocon LG helices, and partial membrane integration of hydrophobic
      nascent-protein sequences. Furthermore, the simulations demonstrate the role of
      specific molecular interactions in the regulation of protein secretion, membrane
      integration, and integral membrane protein topology. Salt-bridge contacts between
      the nascent-protein N-terminus, cytosolic translocon residues, and phospholipid
      head groups are shown to favor conformations of the nascent protein upon early
      stage insertion that are consistent with the Type II (N(cyt)/C(exo)) integral
      membrane protein topology, and extended hydrophobic contacts between the nascent
      protein and the membrane lipid bilayer are shown to stabilize configurations that
      are consistent with the Type III (N(exo)/C(cyt)) topology. These results provide
      a detailed, mechanistic basis for understanding experimentally observed
      correlations between integral membrane protein topology, translocon mutagenesis,
      and nascent-protein sequence.

PMID- 22852865
TI  - Multiple trait multiple interval mapping of quantitative trait loci from inbred
      line crosses.
AB  - BACKGROUND: Although many experiments have measurements on multiple traits, most
      studies performed the analysis of mapping of quantitative trait loci (QTL) for
      each trait separately using single trait analysis. Single trait analysis does not
      take advantage of possible genetic and environmental correlations between traits.
      In this paper, we propose a novel statistical method for multiple trait multiple
      interval mapping (MTMIM) of QTL for inbred line crosses. We also develop a novel
      score-based method for estimating genome-wide significance level of putative QTL
      effects suitable for the MTMIM model. The MTMIM method is implemented in the
      freely available and widely used Windows QTL Cartographer software. RESULTS:
      Throughout the paper, we provide compelling empirical evidences that: (1) the
      score-based threshold maintains proper type I error rate and tends to keep false
      discovery rate within an acceptable level; (2) the MTMIM method can deliver
      better parameter estimates and power than single trait multiple interval mapping
      method; (3) an analysis of Drosophila dataset illustrates how the MTMIM method
      can better extract information from datasets with measurements in multiple
      traits. CONCLUSIONS: The MTMIM method represents a convenient statistical
      framework to test hypotheses of pleiotropic QTL versus closely linked
      nonpleiotropic QTL, QTL by environment interaction, and to estimate the total
      genotypic variance-covariance matrix between traits and to decompose it in terms
      of QTL-specific variance-covariance matrices, therefore, providing more details
      on the genetic architecture of complex traits.

PMID- 22852866
TI  - Acute liver failure due to disseminated herpes simplex virus following
      thymectomy.

PMID- 22852868
TI  - Staff attitudes towards sexuality in relation to gender of people with
      intellectual disability: a qualitative study.
AB  - BACKGROUND: Research has found staff attitudes regarding the sexuality of people
      with intellectual disability (ID) to be negative but influenced by several
      factors. The current study aimed to examine whether gender of people with ID
      affects such attitudes. METHOD: Semistructured interviews were completed with 10
      staff members and analysed using thematic analysis. RESULTS: Results indicated 3
      themes: Women are perceived as sexually innocent, men as more sexually motivated,
      and motivations for sexual relationships are perceived to differ between men and
      women with ID. CONCLUSION: The study indicates unfavourable attitudes towards
      sexuality in individuals with ID that correlate with traditional, restricted
      gender stereotypes. The identification of these themes highlights the importance
      of considering gender when supporting the sexuality of people with ID.

PMID- 22852867
TI  - Changing epidemiologic patterns of deliberate self poisoning in a rural district
      of Sri Lanka.
AB  - BACKGROUND: Acute poisoning is a major public health issue in many parts of the
      world. The epidemiology and the mortality rate is higher in low and middle income
      countries, including Sri Lanka. The aim of this study was to provide details
      about the epidemiology of acute poisoning in a rural Sri Lankan district and to
      identify the changing patterns and epidemiology of poisoning. METHODS: A
      prospective study was conducted from September 2008 to January 2010 in all
      hospitals with inpatient facilities in Anuradhapura district of North Central
      Province of Sri Lanka. Acute poisoning data was extracted from patient charts.
      Selected data were compared to the data collected from a 2005 study in 28
      hospitals. RESULTS: There were 3813 poisoned patients admitted to the hospitals
      in the Anuradhapura district over 17 months. The annual population incidence was
      447 poisoning cases per 100,000 population. The total number of male and female
      patients was approximately similar, but the age distribution differed by gender.
      There was a very high incidence of poisoning in females aged 15-19, with an
      estimated cumulative incidence of 6% over these five years. Although, pesticides
      are still the most common type of poison, medicinal drug poisonings are now 21%
      of the total and have increased 1.6 fold since 2005. CONCLUSIONS: Acute poisoning
      remains a major public health problem in rural Sri Lanka and pesticide poisoning
      remains the most important poison. However, cases of medicinal drug poisoning
      have recently dramatically increased. Youth in these rural communities remain
      very vulnerable to acute poisoning and the problem is so common that school-based
      primary prevention programs may be worthwhile.Lalith Senarathna, Shaluka F
      Jayamanna, Patrick J Kelly, Nick A Buckley,michael J Dibley, Andrew H Dawson.
      These authors contributed equally to this work.

PMID- 22852869
TI  - Evaluation of emerging biomarkers in cardiovascular risk stratification of
      hypertensive patients: a 2-year study.
AB  - OBJECTIVE: To evaluate if there is a correlation between some new emerging
      biomarkers, such as lipoprotein(a) (Lp[a]), apo(a) isoform phenotyping, soluble
      advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L), serum
      myeloperoxidase (MPO), and cardiovascular risk stratification. RESEARCH DESIGN
      AND METHODS: Three hundred patients were enrolled in this open-label, case
      control design trial: 156 hypertensive patients and 144 healthy subjects as
      control group. Hypertensive patients were treated according to the latest ESH/ESC
      guidelines, until the desirable goal of systolic blood pressure (SBP)<140 mmHg,
      and diastolic blood pressure (DBP)<90 mmHg was reached. We evaluated at baseline
      and after 6, 12, 18, and 24 months: SBP, DBP, lipid profile, Lp(a), apo(a)
      isoform phenotyping, sRAGE, sCD40L, and MPO. RESULTS: Hypertensive patients
      presented higher levels of blood pressure, Lp(a), sCD40L, and MPO and lower
      levels of sRAGE compared with controls. We observed a decrease of blood pressure,
      Lp(a), sCD40L, and MPO and an increase of sRAGE after anti-hypertensive
      treatment. Moreover we observed moderate, but statistically significant,
      correlations between blood pressure decrease and Lp(a), MPO, and sCD40L decrease
      and between blood pressure decrease and sRAGE increase. There was also a modest,
      positive correlation between low molecular weight apo(a) isoforms and
      hypertension. A limitation of this study is that we cannot exclude a role for
      lifestyle measures. Furthermore the studied markers seem to improve with blood
      pressure lowering treatment, but we do not have enough statistical power to
      definitely state which drug used has a specific action on the various variables
      measured. CONCLUSION: Lp(a), sRAGE, MPO, sCD40L, and low molecular weight apo(a)
      isoforms are associated with hypertension and may represent an increased
      cardiovascular risk. Longer studies are needed to see if these parameters can be
      also used to predict specific complications linked to hypertension.

PMID- 22852870
TI  - Efficacy and safety of celecoxib versus diclofenac and omeprazole in elderly
      arthritis patients: a subgroup analysis of the CONDOR trial.
AB  - OBJECTIVE: To compare the safety and efficacy of celecoxib versus diclofenac slow
      release (SR) plus omeprazole in elderly arthritis patients. RESEARCH DESIGN AND
      METHODS: Patients aged>=65 years, with osteoarthritis and/or rheumatoid
      arthritis, at high gastrointestinal (GI) risk who participated in the CONDOR
      trial (Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis
      and Rheumatoid Arthritis) were included in this subanalysis. CONDOR was a 6-month
      prospective, double-blind, randomized, parallel-group, multicenter, international
      study comparing treatment with celecoxib 200 mg twice daily (BID) versus
      diclofenac SR 75 mg BID plus omeprazole 20 mg daily. MAIN OUTCOME MEASURES: The
      primary end point was a composite of Clinically Significant Upper and Lower GI
      Events adjudicated by an independent blinded expert committee. Efficacy was
      determined by the Patient's Global Assessment of Arthritis. RESULTS: A total of
      2446 patients aged>=65 years were included in the intent-to-treat (ITT)
      population (n=1219 celecoxib; n=1227 diclofenac). Eight patients in the celecoxib
      group and 52 in the diclofenac group were adjudicated as having Clinically
      Significant Upper and Lower GI events (adjusted odds ratio: 6.27; p<0.0001).
      Clinically significant reductions in hemoglobin (>=2 g/dL) and/or hematocrit
      (>=10%) were observed in 23 patients in the celecoxib group and in 76 in the
      diclofenac group (relative risk: 3.22 [95% confidence interval: 2.04-5.07];
      p<0.0001). Incidence of moderate-to-severe abdominal symptoms and discontinuation
      of treatment due to GI adverse events (AEs) were lower in the celecoxib group.
      The Patient's Global Assessment of Arthritis score least squares mean change from
      baseline to final visit and percentage of patients rating treatment efficacy as
      good/very good at baseline and final visit were similar in both groups.
      LIMITATIONS: The dose of celecoxib used is consistent with the European label for
      the management of osteoarthritis and may not reflect what is commonly prescribed
      in current clinical practice in the United States. The data were obtained in a
      clinical trial setting where patients were enrolled based on specific inclusion
      and exclusion criteria; as such, the patients may not be broadly representative
      of the patient population in a general practice setting. CONCLUSIONS: Efficacy
      was comparable in the two treatment groups. There were fewer endpoints as well as
      fewer GI AEs reported in patients treated with celecoxib compared with
      diclofenac. These data may help physicians in their treatment decisions for
      elderly patients with arthritis.

PMID- 22852871
TI  - Repeat stool testing for Clostridium difficile using enzyme immunoassay in
      patients with inflammatory bowel disease increases diagnostic yield.
AB  - BACKGROUND: The incidence and severity of Clostridium difficile infection (CDI)
      in patients with inflammatory bowel disease (IBD) is increasing. CDI is diagnosed
      by toxin enzyme immunoassay (EIA) or real-time polymerase chain reaction (PCR)
      performed on stool samples. An earlier study evaluating EIA in IBD patients with
      CDI suggested that more than one stool sample be tested to increase diagnostic
      yield. We investigated whether repeat stool testing improves diagnostic accuracy
      for CDI in hospitalized IBD patients compared to hospitalized patients with CDI
      and no IBD. METHODS: We performed retrospective data analysis from January 2005
      May 2011 on 63,086 hospitalized patients who were tested for CDI using EIA or
      PCR. Of these, 2579 patients had IBD. Transition probabilities were calculated
      based on results from repeated tests. RESULTS: Inclusive of all inpatients tested
      for CDI, 56,583 were tested using toxin EIA and 6503 were tested using PCR. In
      patients with no IBD, the first stool sample tested was positive in 90% and 94%
      with EIA and PCR respectively. In IBD patients tested using EIA, 101 were
      diagnosed with CDI. The first stool sample tested was positive in 81% of
      patients. Successive second and third stool samples yielded additional 14% and 5%
      CDI positive IBD patients. CONCLUSIONS: Approximately one in five IBD patients
      with CDI required repeat testing to yield a positive result with EIA. There are
      minimal diagnostic gains of repeat testing by EIA or PCR in patients without IBD.
      We recommend repeat stool testing for CDI when using EIA to increase diagnostic
      yield in IBD patients.

PMID- 22852873
TI  - In African American type 2 diabetic patients, is vitamin D deficiency associated
      with lower blood levels of hydrogen sulfide and cyclic adenosine monophosphate,
      and elevated oxidative stress?
AB  - African Americans (AA) have a higher incidence of cardiovascular disease and
      vitamin D (VD) deficiency compared with Caucasians. Hydrogen sulfide (H(2)S) is
      an important signaling molecule. This study examined the hypothesis that blood
      levels of H(2)S are lower in AA type 2 diabetic patients (T2D). Fasting blood was
      obtained from T2D and healthy controls. Results showed a significant decrease in
      plasma levels of cyclic adenosine monophosphate (cAMP) and H(2)S in AA T2D but
      not in Caucasian T2D when compared with those of respective age- and race-matched
      healthy controls. Plasma VD levels were significantly lower in AA T2D compared
      with Caucasian T2D. Cell culture studies demonstrate that 1,25(OH)(2)-VD
      supplementation significantly increased expression of cystathionine-gamma-lyase
      (CSE), H(2)S formation, and cAMP secretion, but decreased reactive oxygen species
      in high glucose-treated U937 monocytes. This suggests that VD supplementation
      upregulates CSE and H(2)S formation and decreases oxidative stress, and that VD
      deficiency may contribute to the malfunctioning of H(2)S signaling and thus a
      higher incidence of vascular inflammation in AA. These results lead to the
      hypothesis that VD supplementation can replenish blood concentrations of H(2)S
      and cAMP and lower oxidative stress and cardiovascular disease in AA T2D.

PMID- 22852872
TI  - Splenomegaly in myelofibrosis--new options for therapy and the therapeutic
      potential of Janus kinase 2 inhibitors.
AB  - Splenomegaly is a common sign of primary myelofibrosis (PMF), post-polycythemia
      vera myelofibrosis (post-PV MF), and post-essential thrombocythemia myelofibrosis
      (post-ET MF) that is associated with bothersome symptoms, which have a
      significant negative impact on patients' quality of life. It may also be present
      in patients with advanced polycythemia vera (PV) or essential thrombocythemia
      (ET). Until recently, none of the therapies used to treat MF were particularly
      effective in reducing splenomegaly. The discovery of an activating Janus kinase 2
      (JAK2) activating mutation (JAK2V617F) that is present in almost all patients
      with PV and in about 50-60 % of patients with ET and PMF led to the initiation of
      several trials investigating the clinical effectiveness of various JAK2 (or
      JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. Some of
      these trials have documented significant clinical benefit of JAK inhibitors,
      particularly in terms of regression of splenomegaly. In November 2011, the US
      Food and Drug Administration approved the use of the JAK1- and JAK2-selective
      inhibitor ruxolitinib for the treatment of patients with intermediate or high
      risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review
      discusses current therapeutic options for splenomegaly associated with primary or
      secondary MF and the treatment potential of the JAK inhibitors in this setting.

PMID- 22852874
TI  - Bioinformatic cis-element analyses performed in Arabidopsis and rice disclose
      bZIP- and MYB-related binding sites as potential AuxRE-coupling elements in auxin
      mediated transcription.
AB  - BACKGROUND: In higher plants, a diverse array of developmental and growth-related
      processes is regulated by the plant hormone auxin. Recent publications have
      proposed that besides the well-characterized Auxin Response Factors (ARFs) that
      bind Auxin Response Elements (AuxREs), also members of the bZIP- and MYB
      transcription factor (TF) families participate in transcriptional control of
      auxin-regulated genes via bZIP Response Elements (ZREs) or Myb Response Elements
      (MREs), respectively. RESULTS: Applying a novel bioinformatic algorithm, we
      demonstrate on a genome-wide scale that singular motifs or composite modules of
      AuxREs, ZREs, MREs but also of MYC2 related elements are significantly enriched
      in promoters of auxin-inducible genes. Despite considerable, species-specific
      differences in the genome structure in terms of the GC content, this enrichment
      is generally conserved in dicot (Arabidopsis thaliana) and monocot (Oryza sativa)
      model plants. Moreover, an enrichment of defined composite modules has been
      observed in selected auxin-related gene families. Consistently, a bipartite
      module, which encompasses a bZIP-associated G-box Related Element (GRE) and an
      AuxRE motif, has been found to be highly enriched. Making use of transient
      reporter studies in protoplasts, these findings were experimentally confirmed,
      demonstrating that GREs functionally interact with AuxREs in regulating auxin
      mediated transcription. CONCLUSIONS: Using genome-wide bioinformatic analyses,
      evolutionary conserved motifs have been defined which potentially function as
      AuxRE-dependent coupling elements to establish auxin-specific expression
      patterns. Based on these findings, experimental approaches can be designed to
      broaden our understanding of combinatorial, auxin-controlled gene regulation.

PMID- 22852875
TI  - Late evaluation of the relationship between morphological and functional renal
      changes and hypertension after non-operative treatment of high-grade renal
      injuries.
AB  - OBJECTIVE: To evaluate the anatomical and functional renal alterations and the
      association with post-traumatic arterial hypertension. METHODS: The studied
      population included patients who sustained high grades renal injury (grades III
      to V) successfully non-operative management after staging by computed tomography
      over a 16-year period. Beyond the review of medical records, these patients were
      invited to the following protocol: clinical and laboratory evaluation, abdominal
      computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and
      ambulatory blood pressure monitoring. The hypertensive patients also were
      submitted to dynamic renal scintigraphy (99mTc EC), using captopril stimulation
      to verify renal vascular etiology. RESULTS: Of the 31 patients, there were
      thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular
      lesions), and two grade V injuries. All the patients were asymptomatic and an
      average follow up post-injury of 6.4 years. None had abnormal BUN or seric
      creatinine. The percentage of renal volume reduction correlates with the severity
      as defined by OIS. There was no evidence of renal artery stenosis in Magnetic
      Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage
      of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade
      III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients
      (19.4%) had severe compromised function (< 30%). There was statistically
      significant difference in the decrease in renal function between parenchymal and
      vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood
      pressure monitoring detected nine patients (29%) with post-traumatic
      hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial
      history of arterial hypertension, 66.7% had grade III renal injury, and average
      post-injury time was 7.8 years. Seven patients had negative captopril renography.
      CONCLUSIONS: Late results of renal function after conservative treatment of high
      grades renal injuries are favorable, except for patients with grades IV with
      vascular injuries and grade V renal injuries. Moreover, arterial hypertension
      does not correlate with the grade of renal injury or reduction of renal function.

PMID- 22852876
TI  - Detrusor myectomy: long-term functional outcomes.
AB  - OBJECTIVES: Detrusor myectomy is a recognized method of bladder augmentation for
      treating refractory detrusor overactivity. Herein we report the long-term
      outcomes of this procedure at the University Hospital of Wales in Cardiff, UK.
      METHODS: Detrusor myectomy was carried out in 33 patients (7 males, 26 females)
      with urodynamically proven detrusor overactivity between 1995 and 2002. The mean
      patient age was 33 years (range 5-62). A total of 18 patients had idiopathic
      detrusor overactivity, whereas 15 had neurogenic detrusor overactivity. RESULTS:
      A total of 24 patients had a detrusor myectomy alone, whereas eight patients had
      a detrusor myectomy with implantation of artificial urinary sphincter. One
      patient had detrusor myectomy with transuretero-ureterostomy. The mean follow up
      was 148 months (range 108-192). A total of 10 of the 18 patients with idiopathic
      detrusor overactivity (55.5%) and six of the 15 patients with neurogenic detrusor
      overactivity (40%) showed marked improvement in symptoms. Detrusor overactivity
      was completely abolished in 11 patients and significantly reduced in five.
      Postoperatively, mean cystometric capacity improved from 290 to 458 mL, whereas
      mean maximum amplitude of detrusor contraction was reduced from 44 cm/H(2) O to
      20 cm/H(2) O. An overall success rate of 48.5% (16/33 patients) was achieved.
      Intermittent self catheterization was needed to achieve bladder emptying in 12 of
      the 16 (75%) patients. Of the remaining 17 patients who did not improve, six had
      CLAM enterocystoplasty carried out and two await the operation. An ileal conduit
      diversion and suprapubic catheter insertion was carried out in one patient each,
      whereas seven patients declined any further intervention. CONCLUSIONS: Detrusor
      myectomy offers a reasonable long-term success rate to patients undergoing
      surgical treatment for refractory detrusor overactivity.

PMID- 22852877
TI  - Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella
      multocida toxin-induced G protein signalling.
AB  - BACKGROUND: Lipopolysaccharide (LPS)-triggered Toll-like receptor (TLR) 4
      signalling belongs to the key innate defence mechanisms upon infection with Gram
      negative bacteria and triggers the subsequent activation of adaptive immunity.
      There is an active crosstalk between TLR4-mediated and other signalling cascades
      to secure an effective immune response, but also to prevent excessive
      inflammation. Many pathogens induce signalling cascades via secreted factors that
      interfere with TLR signalling to modify and presumably escape the host response.
      In this context heterotrimeric G proteins and their coupled receptors have been
      recognized as major cellular targets. Toxigenic strains of Gram-negative
      Pasteurella multocida produce a toxin (PMT) that constitutively activates the
      heterotrimeric G proteins Galphaq, Galpha13 and Galphai independently of G
      protein-coupled receptors through deamidation. PMT is known to induce signalling
      events involved in cell proliferation, cell survival and cytoskeleton
      rearrangement. RESULTS: Here we show that the activation of heterotrimeric G
      proteins through PMT suppresses LPS-stimulated IL-12p40 production and eventually
      impairs the T cell-activating ability of LPS-treated monocytes. This inhibition
      of TLR4-induced IL-12p40 expression is mediated by Galphai-triggered signalling
      as well as by Gbetagamma-dependent activation of PI3kinase and JNK.Taken together
      we propose the following model: LPS stimulates TLR4-mediated activation of the
      NFKB-pathway and thereby the production of TNF-alpha, IL-6 and IL-12p40. PMT
      inhibits the production of IL-12p40 by Galphai-mediated inhibition of adenylate
      cyclase and cAMP accumulation and by Gbetagamma-mediated activation of PI3kinase
      and JNK activation. CONCLUSIONS: On the basis of the experiments with PMT this
      study gives an example of a pathogen-induced interaction between G protein
      mediated and TLR4-triggered signalling and illustrates how a bacterial toxin is
      able to interfere with the host's immune response.

PMID- 22852878
TI  - Effectiveness of smoking-cessation interventions for urban hospital patients:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Hospitalization may be a particularly important time to promote
      smoking cessation, especially in the immediate post-discharge period. However,
      there are few studies to date that shed light on the most effective or cost
      effective methods to provide post-discharge cessation treatment, especially among
      low-income populations and those with a heavy burden of mental illness and
      substance use disorders. METHODS/DESIGN: This randomized trial will compare the
      effectiveness and cost-effectiveness of two approaches to smoking cessation
      treatment among patients discharged from two urban public hospitals in New York
      City. During hospitalization, staff will be prompted to ask about smoking and to
      offer nicotine replacement therapy (NRT) on admission and at discharge. Subjects
      will be randomized on discharge to one of two arms: one arm will be proactive
      multi-session telephone counseling with motivational enhancement delivered by
      study staff, and the other will be a faxed or online referral to the New York
      State Quitline. The primary outcome is 30-day point-prevalence abstinence from
      smoking at 6-month follow-up post-discharge. We will also examine cost
      effectiveness from a societal and a payer perspective, as well as explore
      subgroup analyses related to patient location of hospitalization, race/ethnicity,
      immigrant status, and inpatient diagnosis. DISCUSSION: This study will explore
      issues of implementation feasibility in a post-hospitalization patient
      population, as well as add information about the effectiveness and cost
      effectiveness of different strategies for designing smoking cessation programs
      for hospitalized patients. TRIAL REGISTRATION: Clinicaltrials.gov ID#
      NCT01363245.

PMID- 22852879
TI  - Hygroscopic and chemical properties of aerosols collected near a copper smelter:
      implications for public and environmental health.
AB  - Particulate matter emissions near active copper smelters and mine tailings in the
      southwestern United States pose a potential threat to nearby environments owing
      to toxic species that can be inhaled and deposited in various regions of the body
      depending on the composition and size of the particles, which are linked by
      particle hygroscopic properties. This study reports the first simultaneous
      measurements of size-resolved chemical and hygroscopic properties of particles
      next to an active copper smelter and mine tailings by the towns of Hayden and
      Winkelman in southern Arizona. Size-resolved particulate matter samples were
      examined with inductively coupled plasma mass spectrometry, ion chromatography,
      and a humidified tandem differential mobility analyzer. Aerosol particles
      collected at the measurement site are enriched in metals and metalloids (e.g.,
      arsenic, lead, and cadmium) and water-uptake measurements of aqueous extracts of
      collected samples indicate that the particle diameter range of particles most
      enriched with these species (0.18-0.55 MUm) overlaps with the most hygroscopic
      mode at a relative humidity of 90% (0.10-0.32 MUm). These measurements have
      implications for public health, microphysical effects of aerosols, and regional
      impacts owing to the transport and deposition of contaminated aerosol particles.

PMID- 22852880
TI  - Exploring improvements in patient logistics in Dutch hospitals with a survey.
AB  - BACKGROUND: Research showed that promising approaches such as benchmarking,
      operations research, lean management and six sigma, could be adopted to improve
      patient logistics in healthcare. To our knowledge, little research has been
      conducted to obtain an overview on the use, combination and effects of approaches
      to improve patient logistics in hospitals. We therefore examined the approaches
      and tools used to improve patient logistics in Dutch hospitals, the reported
      effects of these approaches on performance, the applied support structure and the
      methods used to evaluate the effects. METHODS: A survey among experts on patient
      logistics in 94 Dutch hospitals. The survey data were analysed using cross
      tables. RESULTS: Forty-eight percent of all hospitals participated. Ninety-eight
      percent reported to have used multiple approaches, 39% of them used five or more
      approaches. Care pathways were the preferred approach by 43% of the hospitals,
      followed by business process re-engineering and lean six sigma (both 13%).
      Flowcharts were the most commonly used tool, they were used on a regular basis by
      94% of the hospitals. Less than 10% of the hospitals used data envelopment
      analysis and critical path analysis on a regular basis. Most hospitals (68%)
      relied on external support for process analyses and education on patient
      logistics, only 24% had permanent internal training programs on patient
      logistics. Approximately 50% of the hospitals that evaluated the effects of
      approaches on efficiency, throughput times and financial results, reported that
      they had accomplished their goals. Goal accomplishment in general hospitals
      ranged from 63% to 67%, in academic teaching hospitals from 0% to 50%, and in
      teaching hospitals from 25% to 44%. More than 86% performed an evaluation, 53%
      performed a post-intervention measurement. CONCLUSIONS: Patient logistics
      appeared to be a rather new subject as most hospitals had not selected a single
      approach, they relied on external support and they did not have permanent
      training programs. Hospitals used a combination of approaches and tools, about
      half of the hospitals reported goal accomplishment and no approach seemed to
      outperform the others. To make improvement efforts more successful, research
      should be conducted into the selection and application of approaches, their
      contingency factors, and goal-setting procedures.

PMID- 22852881
TI  - Bending the cost curve through market-based incentives.

PMID- 22852882
TI  - Patient access to medical devices--a comparison of U.S. and European review
      processes.

PMID- 22852883
TI  - A systemic approach to containing health care spending.

PMID- 22852884
TI  - Comparison of power and EMG during 6-s all-out cycling between young and older
      women.
AB  - To investigate the effects of ageing on the neural control strategies governing
      sprint cycling on a friction-loaded cycle-ergometer, 10 older (aged 70-83 yr) and
      8 young (aged 19-35 yr) healthy women completed seven 6-s all-out cycling trials
      against varying loads. Root mean square (RMS), median frequency and muscle fibre
      conduction velocity were determined from the vastus lateralis of the dominant
      limb during each pedal stroke. Peak power was 43% lower in the older group
      compared to the younger (p < 0.001) and was accompanied by a significantly lower
      RMS (p < 0.05). No differences were observed in the other electromyography (EMG)
      parameters between the groups (p > 0.05). DeltaRMS from the first to the sixth
      second during each trial was found to increase significantly with the development
      of power output in both groups (p < 0.05). For the first time during an all-out 6
      s cycle trial, it has been demonstrated that older women's lower mechanical power
      output was accompanied by a significantly lower RMS, which indicates a decline in
      either the number of active of motor units or a reduced discharge rate. Hence,
      changes in motor units can be regarded as a contributory factor to the decline of
      muscle power with advancing age. Overall, though, similar neural strategies are
      adopted in both younger and older populations.

PMID- 22852885
TI  - Association of vitamin D receptor gene polymorphisms with colon cancer.
AB  - OBJECTIVE: In this study, we investigated the association of two vitamin D
      receptor (VDR) polymorphisms BsmI and TaqI with colon cancer in a Caucasian
      population. METHODS: The VDR gene polymorphisms BsmI and TaqI were detected by
      polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)
      genotyping assays by using endonucleases BsmI and TaqI, and an agarose gel
      electrophoresis technique in a series of 43 colon cancer patients and 42 healthy
      controls. RESULTS: Allele frequencies and genotype distributions were found to be
      similar in both cases and controls. When homozygous carriers and heterozygotes
      were combined for each allele, alleles B and T were found to be more common in
      the control group (p=0.039, chi(2)=4.276, odds ratio [OR]=0.312, 95% confidence
      interval [CI]=0.100-0.973 and p=0.039, chi(2)=4.258, OR=0.254, 95% CI=0.064
      1.000, respectively). When genotypes were analyzed as pairs, the Bb/TT variant
      was higher in the control group at a statistically high significance (p=0.001,
      chi(2)=11.854, OR=0.122, 95% CI=0.032-0.460). CONCLUSION: The alleles B and T and
      the genotype combination Bb/TT were found to be higher in the control group, and
      thus BsmI and TaqI polymorphisms of the VDR gene may be possible risk factors for
      colorectal carcinogenesis.

PMID- 22852990
TI  - Introduction.

PMID- 22852991
TI  - Racial and ethnic diversity in senior centers: comparing participant
      characteristics in more and less multicultural settings.
AB  - The 2008 Health Indicators Project surveyed a probability sample (N = 1,870) of
      New York City senior center participants. Attendees of racially and ethnically
      diverse and nondiverse senior centers were compared across 5 domains:
      demographics; health and quality of life; social support networks; neighborhood
      perceptions and engagement; health service access/utilization. Although
      homogeneous and diverse center participants demonstrate similar health and
      quality-of-life outcomes, those from diverse centers demonstrate greater risk of
      social isolation, receive less family support, and more likely seek medical care
      from hospitals or community clinics. Implications and future directions for
      research, practice and policy are discussed.

PMID- 22852992
TI  - Advance directives among Korean American older adults: knowledge, attitudes, and
      behavior.
AB  - The study objective was to explore knowledge, attitudes, and behavior about
      advance directives and how cultural values influence these beliefs. Three focus
      groups with 23 Korean American older adults were conducted. Advance directives
      were seen as helpful for ensuring that preferences for unwanted end-of-life
      treatment are honored and for relieving the decision-making burden on family
      members. However, some viewed completing advance directives as contrary to
      focusing on living. Culturally competent education about advance directives for
      Korean American older adults is necessary to help them make informed decisions
      about end-of-life care and informing family and health care providers of these
      preferences.

PMID- 22852993
TI  - Structuring mental health within senior services: a case study of an outpatient
      mental health clinic serving Latinos.
AB  - The article presents a case study of an outpatient mental health clinic serving
      Latino older adults. The study explored staff perceptions on the clinic
      development and the context within an immigrant multicultural community. The
      study used in-depth, semistructured interviews with support staff, clinical
      social workers, and administrators. Interviews were analyzed using a thematic
      content analysis. The mental health clinic formation was perceived by staff as an
      ecological process stemming from the needs of the Latino immigrant senior
      clients. A close knit and interdependent culture allowed the clinic to adjust to
      diversity and changing cultural contexts.

PMID- 22852994
TI  - Gerontological social workers' perceived efficacy for influencing client
      outcomes.
AB  - Using a sample of practitioners (n = 269) from the 2004 National Study of
      Licensed Social Workers, this article employs a quality assurance structure
      process-outcome model to examine factors at the practitioner, workplace, and
      service delivery levels that influence the perceived efficacy of licensed
      gerontological social workers to affect client outcomes in the context of a
      highly challenging health care environment. A regression model accounted for
      33.9% of the variance (adjusted R (2) = .291) in perceived efficacy with 3
      aspects of service delivery satisfaction having significant effects: ability to
      address complex/chronic care, to influence the design of services, and to help
      clients navigate the system.

PMID- 22852995
TI  - Cancer screening barriers for community-based older Hispanics and Caucasians.
AB  - Despite advances in screening and early detection, ethnic minority populations,
      ages 65 and older, are less likely than Caucasians to participate in cancer
      screening services. Empirical research indicates that older ethnic minorities
      have cultural values that influence their behaviors. Addressing culturally
      relevant communication to better understand those values may increase
      participation in cancer screening. The study reported is a secondary analysis of
      qualitative data gathered from focus groups. Utilizing an interdisciplinary
      analytical lens, we compared older Hispanic and Caucasian's cultural values and
      their screening behaviors. Suggested psychosocial interventions are discussed to
      assist providers in their ongoing efforts to promote cancer screening.

PMID- 22852997
TI  - Highly electron-deficient hexaazapentacenes and their dihydro precursors.
AB  - Novel silylethynylated N-heteropentacenes that have three adjacent pyrazine rings
      at the center of a pentacene backbone are reported. These hexaazapentacenes
      exhibit a record low energy level of lowest unoccupied molecular orbital (LUMO)
      for N-heteropentacenes and thus are able to oxidize dihydroanthracene to
      anthracene. Their synthetic precursors are the corresponding
      dihydrohexaazapentacenes, which exhibit interesting H-bonding.

PMID- 22852998
TI  - Probing the effects of lipid substitution on polycation mediated DNA aggregation:
      a molecular dynamics simulations study.
AB  - Understanding the molecular mechanism of DNA aggregation and condensation is of
      importance to DNA packaging in cells, and applications of gene delivery therapy.
      Modifying polycations such as polyethylenimine with lipid substitution was found
      to improve the performance of polycationic gene carriers. However, the role of
      the lipid substitution in DNA binding and aggregation is not clear and remains to
      be probed at the molecular level. In this work, we elucidated the role of lipid
      substitution through a series of all-atom molecular dynamics simulations on DNA
      aggregation mediated by lipid modified polyethylenimine (lmPEI). We found that
      the lipids associate significantly with one another, which links the lmPEIs and
      serves as a mechanism of aggregating the DNAs and stabilizing the formed
      polyplex. In addition, some lipid tails on the lmPEIs stay at the periphery of
      the lmPEI/DNA polyplex and may provide a mechanism for hydrophobic interactions.
      The enhanced stability and hydrophobicity might contribute to better cellular
      uptake of the polyplexes.

PMID- 22852999
TI  - Zygomycosis over-infection during voriconazole therapy for aspergillosis in a
      heart transplant patient, successfully treated with liposomal amphotericin and
      posaconazole.
AB  - Aspergillosis and zygomycosis are life-threatening fungal infections in
      immunocompromised patients. We report a heart transplant recipient with an early
      pulmonary invasive aspergillosis successfully treated with association of
      voriconazole and caspofungin. Zygomycosis sinusitis, which was diagnosed while he
      still was on voriconazole therapy, was successfully treated with the use of
      combination antifungal therapy including liposomal amphotericin plus posaconazole
      and conservative surgical debridement.

PMID- 22853000
TI  - Expression of S100A4, ephrin-A1 and osteopontin in non-small cell lung cancer.
AB  - BACKGROUND: The metastasis-promoting protein S100A4 induces expression of ephrin
      A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to
      investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small
      cell lung cancer (NSCLC) cell lines, and to characterize the expression of these
      biomarkers in primary tumor tissue from NSCLC patients. METHODS: Four NSCLC cell
      lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin
      expression was analyzed by real time RT-PCR and Western blotting.
      Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed
      on tissue microarrays containing primary tumor samples from a cohort of 217
      prospectively recruited NSCLC patients, and associations with clinicopathological
      parameters were investigated. RESULTS: S100A4 induced ephrin-A1 mRNA and protein
      expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas
      the level of osteopontin was unaffected by S100A4 treatment. In primary tumors,
      moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic
      S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin.
      Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but
      there was no association between S100A4 and osteopontin. Expression levels of
      S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to
      other histological subtypes, and S100A4-positive tumors were smaller and more
      differentiated than tumors without expression. CONCLUSIONS: Our findings suggest
      that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and
      further investigation of their potential use as biomarkers in NSCLC is warranted.

PMID- 22853002
TI  - Psychosocial problems of Pakistani parents of Thalassemic children: a cross
      sectional study done in Bahawalpur, Pakistan.
AB  - BACKGROUND: Thalassemia is a blood disorder passed down through families
      (inherited) in which the body makes an abnormal form of hemoglobin. This disorder
      results in excessive destruction of red blood cells, and there is no effective
      treatment. Patients require lifelong blood transfusion, usually started within 6
      to 12 months of birth of patient, which on other hand has its own complications.
      It is a chronic disease that manifests so early in life that it leads to
      psychological and social problems for parents . We focused on parents to assess
      the impact of their child's disease. OBJECTIVE: To determine the psychosocial
      problems of parents of thalassemic children. METHODS: This cross sectional study
      was conducted among the parents of thalassemic children attending THALASSEMIA
      CENTRE, BAHAVAL VICTORIA HOSPITAL (BVH), BAHAWALPUR, PAKISTAN during the year
      2011. A self designed questionnaire was used that contained questions regarding
      psychological and social aspects. Patient Health Questionnaire-9 (PHQ-9) was used
      to assess the depression of parents of thalassemic children. RESULTS: Of the 100
      parents interviewed, the majority were mothers (71%) , with a mean age of 32 +/-
      8.07 years for both sexes. 29 percent of the parents had moderate to severe
      depression, 16 percent had sleep disturbances. 56 percent were downgraded by
      relatives. There was a significant relationship between respondent education and
      depression (p < 0.05). CONCLUSION: A substantial number of parents have
      psychosocial problems due to the disease of their child. Parent counseling is
      needed on regular basis.

PMID- 22853003
TI  - Thiol-ene click chemistry: computational and kinetic analysis of the influence of
      alkene functionality.
AB  - The influence of alkene functionality on the energetics and kinetics of radical
      initiated thiol-ene click chemistry has been studied computationally at the CBS
      QB3 level. Relative energetics (DeltaH degrees , DeltaH(++), DeltaG degrees ,
      DeltaG(++)) have been determined for all stationary points along the step-growth
      mechanism of thiol-ene reactions between methyl mercaptan and a series of 12
      alkenes: propene, methyl vinyl ether, methyl allyl ether, norbornene,
      acrylonitrile, methyl acrylate, butadiene, methyl(vinyl)silanediamine, methyl
      crotonate, dimethyl fumarate, styrene, and maleimide. Electronic structure
      calculations reveal the underlying factors that control activation barriers for
      propagation and chain-transfer processes of the step-growth mechanism. Results
      are further extended to predict rate constants for forward and reverse
      propagation and chain-transfer steps (k(P), k(-P), k(CT), k(-CT)) and used to
      model overall reaction kinetics. A relationship between alkene structure and
      reactivity in thiol-ene reactions is derived from the results of kinetic modeling
      and can be directly related to the relative energetics of stationary points
      obtained from electronic structure calculations. The results predict the order of
      reactivity of alkenes and have broad implications for the use and applications of
      thiol-ene click chemistry.

PMID- 22853004
TI  - Carbohydrates and their free radical scavenging capability: a theoretical study.
AB  - A density functional theory (DFT) study on the free radical (OH(*) and OOH(*))
      scavenging properties of some mono- and polysaccharides is presented. Two
      mechanisms, single electron transfer (SET) and hydrogen atom transfer (HAT), are
      considered. The former mechanism is studied by making use of the vertical
      ionization energy and vertical electron affinity of the radicals and
      carbohydrates. It is confirmed that the SET mechanism is not plausible to occur.
      With respect to the HAT, not only does the OH(*) radical react preferably with
      one hydrogen atom bonded to one carbon atom, but also the reaction with a
      hydrogen atom bonded to an oxygen is possible. Finally, it is suggested that the
      carbohydrates are not able to directly scavenge OOH(*).

PMID- 22853001
TI  - Synthesis and profiling of a diverse collection of azetidine-based scaffolds for
      the development of CNS-focused lead-like libraries.
AB  - The synthesis and diversification of a densely functionalized azetidine ring
      system to gain access to a wide variety of fused, bridged, and spirocyclic ring
      systems is described. The in vitro physicochemical and pharmacokinetic properties
      of representative library members are measured in order to evaluate the use of
      these scaffolds for the generation of lead-like molecules to be used in targeting
      the central nervous system. The solid-phase synthesis of a 1976-membered library
      of spirocyclic azetidines is also described.

PMID- 22853005
TI  - The cytological changes of tobacco zygote and proembryo cells induced by beta
      glucosyl Yariv reagent suggest the involvement of arabinogalactan proteins in
      cell division and cell plate formation.
AB  - BACKGROUND: In dicotyledonous plant, the first asymmetric zygotic division and
      subsequent several cell divisions are crucial for proembryo pattern formation and
      later embryo development. Arabinogalactan proteins (AGPs) are a family of
      extensively glycosylated cell surface proteins that are thought to have important
      roles in various aspects of plant growth and development, including
      embryogenesis. Previous results from our laboratory show that AGPs are concerned
      with tobacco egg cell fertilization and zygotic division. However, how AGPs
      interact with other factors involved in zygotic division and proembryo
      development remains unknown. RESULTS: In this study, we used the tobacco in vitro
      zygote culture system and series of meticulous cell biology techniques to
      investigate the roles of AGPs in zygote and proembryo cell division. For the
      first time, we examined tobacco proembryo division patterns detailed to every
      cell division. The bright-field images and statistical results both revealed that
      with the addition of an exogenous AGPs inhibitor, beta-glucosyl Yariv (beta-GlcY)
      reagent, the frequency of aberrant division increased remarkably in cultured
      tobacco zygotes and proembryos, and the cell plate specific locations of AGPs
      were greatly reduced after beta-GlcY treatment. In addition, the accumulations of
      new cell wall materials were also significantly affected by treating with beta
      GlcY. Detection of cellulose components by Calcofluor white stain showed that
      strong fluorescence was located in the newly formed wall of daughter cells after
      the zygotic division of in vivo samples and the control samples from in vitro
      culture without beta-GlcY treatment; while there was only weak fluorescence in
      the newly formed cell walls with beta-GlcY treatment. Immunocytochemistry
      examination with JIM5 and JIM7 respectively against the low- and high-esterified
      pectins displayed that these two pectins located in opposite positions of zygotes
      and proembryos in vivo and the polarity was not affected by beta-GlcY.
      Furthermore, FM4-64 staining revealed that endosomes were distributed in the cell
      plates of proembryos, and the localization pattern was also affected by beta-GlcY
      treatment. These results were further confirmed by subsequent observation with
      transmission electron microscopy. Moreover, the changes to proembryo cell
      organelles induced by beta-GlcY reagent were also observed using fluorescent dye
      staining technique. CONCLUSIONS: These results imply that AGPs may not only
      relate to cell plate position decision, but also to the location of new cell wall
      components. Correlated with other factors, AGPs further influence the zygotic
      division and proembryo pattern establishment in tobacco.

PMID- 22853006
TI  - Air sampling procedures to evaluate microbial contamination: a comparison between
      active and passive methods in operating theatres.
AB  - BACKGROUND: Since air can play a central role as a reservoir for microorganisms,
      in controlled environments such as operating theatres regular microbial
      monitoring is useful to measure air quality and identify critical situations. The
      aim of this study is to assess microbial contamination levels in operating
      theatres using both an active and a passive sampling method and then to assess if
      there is a correlation between the results of the two different sampling methods.
      METHODS: The study was performed in 32 turbulent air flow operating theatres of a
      University Hospital in Southern Italy. Active sampling was carried out using the
      Surface Air System and passive sampling with settle plates, in accordance with
      ISO 14698. The Total Viable Count (TVC) was evaluated at rest (in the morning
      before the beginning of surgical activity) and in operational (during surgery).
      RESULTS: The mean TVC at rest was 12.4 CFU/m3 and 722.5 CFU/m2/h for active and
      passive samplings respectively. The mean in operational TVC was 93.8 CFU/m3 (SD =
      52.69; range = 22-256) and 10496.5 CFU/m2/h (SD = 7460.5; range = 1415.5-25479.7)
      for active and passive samplings respectively. Statistical analysis confirmed
      that the two methods correlate in a comparable way with the quality of air.
      CONCLUSION: It is possible to conclude that both methods can be used for general
      monitoring of air contamination, such as routine surveillance programs. However,
      the choice must be made between one or the other to obtain specific information.

PMID- 22853007
TI  - Difficulties of care-work reconciliation: employed and nonemployed mothers of
      children with intellectual disability.
AB  - BACKGROUND: Whether employed and nonemployed mothers of children with
      intellectual disability (ID) have different experiences with reconciliation
      between care and work has rarely been explored. METHOD: A survey was conducted in
      a county in Taiwan and 487 mothers aged younger than 65 and having a child with
      ID were interviewed face to face at their homes to explore whether there are
      different factors related to the reconciliation between care and work among
      employed and nonemployed mothers. RESULTS: Except for the common ground of
      mothers' health and care demands, logistic regression revealed work flexibility
      and care support were important for employed mothers. In contrast, the success of
      reconciliation for nonemployed mothers was determined by their individual
      characteristics (i.e., age, marital status, family income). CONCLUSIONS:
      Reconciliation policies for mothers with different employment statuses need to
      use different strategies.

PMID- 22853008
TI  - The association between sidewalk length and walking for different purposes in
      established neighborhoods.
AB  - BACKGROUND: Walking in neighborhood environments is undertaken for different
      purposes including for transportation and leisure. We examined whether sidewalk
      availability was associated with participation in, and minutes of neighborhood
      based walking for transportation (NWT) and recreation (NWR) after controlling for
      neighborhood self-selection. METHOD: Baseline survey data from respondents (n =
      1813) who participated in the RESIDential Environment (RESIDE) project (Perth,
      Western Australia) were used. Respondents were recruited based on their plans to
      move to another neighborhood in the following year. Usual weekly neighborhood
      based walking, residential preferences, walking attitudes, and demographics were
      measured. Characteristics of the respondent's baseline neighborhood were measured
      including transportation-related walkability and sidewalk length. A Heckman two
      stage modeling approach (multivariate Probit regression for walking
      participation, followed by a sample selection-bias corrected OLS regression for
      walking minutes) estimated the relative contribution of sidewalk length to NWT
      and NWR. RESULTS: After adjustment, neighborhood sidewalk length and walkability
      were positively associated with a 2.97 and 2.16 percentage point increase in the
      probability of NWT participation, respectively. For each 10 km increase in
      sidewalk length, NWT increased by 5.38 min/wk and overall neighborhood-based
      walking increased by 5.26 min/wk. Neighborhood walkability was not associated
      with NWT or NWR minutes. Moreover, sidewalk length was not associated with NWR
      minutes. CONCLUSIONS: Sidewalk availability in established neighborhoods may be
      differentially associated with walking for different purposes. Our findings
      suggest that large investments in sidewalk construction alone would yield small
      increases in walking.

PMID- 22853009
TI  - Can acid volatile sulfides (AVS) influence metal concentrations in the macrophyte
      Myriophyllum aquaticum?
AB  - The difference between the molar concentrations of simultaneously extracted
      metals (SEM) and acid volatile sulfides (AVS) is widely used to predict metal
      availability toward invertebrates in hypoxic sediments. However, this model is
      poorly investigated for macrophytes. The present study evaluates metal
      accumulation in roots and stems of the macrophyte Myriophyllum aquaticum during a
      54 day lab experiment. The macrophytes, rooting in metal contaminated, hypoxic,
      and sulfide rich field sediments were exposed to surface water with 40% or 90%
      oxygen. High oxygen concentrations in the 90% treatment resulted in dissolution
      of the metal-sulfide complexes and a gradual increase in labile metal
      concentrations during the experiment. However, the general trend of increasing
      availability in the sediment with time was not translated in rising M. aquaticum
      metal concentrations. Processes at the root-sediment interface, e.g., radial
      oxygen loss (ROL) or the release of organic compounds by plant roots and their
      effect on metal availability in the rhizosphere may be of larger importance for
      metal accumulation than the bulk metal mobility predicted by the SEM-AVS model.

PMID- 22853011
TI  - Are Americans ready to solve the weight of the nation?

PMID- 22853010
TI  - Single-session ureteroscopy with holmium laser lithotripsy for multiple stones.
AB  - Multiple stones are found in 20-25% of patients with urolithiasis. The stone
      multiplicity is a powerful adverse factor influencing the treatment outcome after
      shockwave lithotripsy, although guidelines for the treatment of multiple stones
      have not been well established yet. Herein we report our most recent experience
      of a single-session ureteroscopy for multiple stones. Between September 2008 and
      December 2011, 51 patients with multiple stones (total 146 stones) in different
      locations (37unilateral, 14 bilateral) underwent a total of 65 ureteroscopic
      procedures. Operative time, stone-free rates and complications were evaluated.
      Stone-free status was defined as no fragments in the ureter and the absence of >2
      mm fragments in the kidney. The mean stone number per patient was 2.9 +/- 1.7 and
      the mean stone burden (cumulative stone length) was 21.5 +/- 11.6 mm. The mean
      number of procedures was 1.3 +/- 0.6. Overall, the stone-free rate after a single
      session was 80% (41/51). In patients with stone burden <20 mm and >=20 mm, stone
      free rates after a single session were 92% (23/25) and 69% (18/26), respectively.
      Multivariate analysis showed that the stone burden and the presence of impacted
      stones were the factors significantly influencing the treatment outcome. Stone
      location did not have a strong influence on the outcome. No major intraoperative
      complications were identified. Our findings suggest that ureteroscopy is an
      efficient treatment for multiple stones. For patients with stone burden <20 mm,
      either unilaterally or bilaterally, a single session of ureteroscopy is a
      favorable treatment option with a high stone-free rate.

PMID- 22853012
TI  - Medicare and Medicaid spending trends and the deficit debate.

PMID- 22853013
TI  - Overbilling and informed financial consent--a contractual solution.

PMID- 22853015
TI  - Doctors, patients, and lawyers--two centuries of health law.

PMID- 22853016
TI  - Images in clinical medicine. Unexpected swallowing of a knife.

PMID- 22853017
TI  - Clinical problem-solving. Breathtaking journey.

PMID- 22853014
TI  - Combination anastrozole and fulvestrant in metastatic breast cancer.
AB  - BACKGROUND: The aromatase inhibitor anastrozole inhibits estrogen synthesis.
      Fulvestrant binds and accelerates degradation of estrogen receptors. We
      hypothesized that these two agents in combination might be more effective than
      anastrozole alone in patients with hormone-receptor (HR)-positive metastatic
      breast cancer. METHODS: Postmenopausal women with previously untreated metastatic
      disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of
      anastrozole orally every day (group 1), with crossover to fulvestrant alone
      strongly encouraged if the disease progressed, or anastrozole and fulvestrant in
      combination (group 2). Patients were stratified according to prior or no prior
      receipt of adjuvant tamoxifen therapy. Fulvestrant was administered
      intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and
      monthly thereafter. The primary end point was progression-free survival, with
      overall survival designated as a prespecified secondary outcome. RESULTS: The
      median progression-free survival was 13.5 months in group 1 and 15.0 months in
      group 2 (hazard ratio for progression or death with combination therapy, 0.80;
      95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The
      combination therapy was generally more effective than anastrozole alone in all
      subgroups, with no significant interactions. Overall survival was also longer
      with combination therapy (median, 41.3 months in group 1 and 47.7 months in group
      2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank
      test), despite the fact that 41% of the patients in group 1 crossed over to
      fulvestrant after progression. Three deaths that were possibly associated with
      treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not
      differ significantly between the two groups. CONCLUSIONS: The combination of
      anastrozole and fulvestrant was superior to anastrozole alone or sequential
      anastrozole and fulvestrant for the treatment of HR-positive metastatic breast
      cancer, despite the use of a dose of fulvestrant that was below the current
      standard. (Funded by the National Cancer Institute and AstraZeneca; SWOG
      ClinicalTrials.gov number, NCT00075764.).

PMID- 22853019
TI  - Bariatric surgery or medical therapy for obesity.

PMID- 22853020
TI  - Bariatric surgery or medical therapy for obesity.

PMID- 22853021
TI  - Bariatric surgery or medical therapy for obesity.

PMID- 22853023
TI  - Comparative effectiveness of revascularization strategies.

PMID- 22853024
TI  - Comparative effectiveness of revascularization strategies.

PMID- 22853026
TI  - Low-dose abdominal CT for diagnosing appendicitis.

PMID- 22853027
TI  - Low-dose abdominal CT for diagnosing appendicitis.

PMID- 22853029
TI  - Two hundred years of surgery.

PMID- 22853030
TI  - Two hundred years of surgery.

PMID- 22853031
TI  - Association of a HOXB13 variant with breast cancer.

PMID- 22853035
TI  - Images in clinical medicine. Hernia through the foramen of Winslow.

PMID- 22853036
TI  - The ribonuclease Dis3 is an essential regulator of the developmental
      transcriptome.
AB  - BACKGROUND: Dis3 is ribonuclease that acts directly in the processing, turnover,
      and surveillance of a large number of distinct RNA species. Evolutionarily
      conserved from eubacteria to eukaryotes and a crucial component of the RNA
      processing exosome, Dis3 has been shown to be essential in yeast and fly S2
      cells. However, it is not known whether Dis3 has essential functions in a
      metazoan. This study inquires whether Dis3 is required for Drosophila development
      and viability and how Dis3 regulates the transcriptome in the developing fly.
      RESULTS: Using transgenic flies, we show that Dis3 knock down (Dis3KD) retards
      growth, induces melanotic tumor formation, and ultimately results in 2nd instar
      larval lethality. In order to determine whether Dis3KD fly phenotypes were a
      consequence of disrupting developmentally regulated RNA turnover, we performed
      RNA deep sequencing analysis on total RNA isolated from developmentally staged
      animals. Bioinformatic analysis of transcripts from Dis3KD flies reveals
      substantial transcriptomic changes, most notably down-regulation in early
      expressed RNAs. Finally, gene ontology analysis of this early stage shows that
      Dis3 regulates transcripts related to extracellular structure and remodelling,
      neurogenesis, and nucleotide metabolism. CONCLUSIONS: We conclude that Dis3 is
      essential for early Drosophila melanogaster development and has specific and
      important stage-specific roles in regulating RNA metabolism. In showing for the
      first time that Dis3 is required for the development of a multicellular organism,
      our work provides mechanistic insight into how Dis3-either independent of or
      associated with the RNA processing exosome-participates in cell type-specific RNA
      turnover in metazoan development.

PMID- 22853037
TI  - Replacing xylene with n-heptane for paraffin embedding.
AB  - In standard histological technique, aromatic solvents such as xylene and toluene
      are used as clearing agents between ethanol dehydration and paraffin embedding.
      In addition, these solvents are used for de-waxing paraffin sections.
      Unfortunately, these solvents are harmful and therefore adequate substitutes
      would be useful. We suggest the use of n-heptane as a convenient substitute for
      xylene. Paraffin sections of rat tissues processed with n-heptane and stained
      with hematoxylin-eosin or Masson's trichrome showed proper embedment, well
      preserved morphology and excellent staining.

PMID- 22853039
TI  - Poppy seed oil protection of the hippocampus after cerebral ischemia and re
      perfusion in rats.
AB  - The brain is highly sensitive to hypoxia; this is true particularly of parts that
      are crucial for cognitive function. The effects of hypoxia are especially
      dramatic in the hippocampus. We evaluated the potential protective effects of
      poppy seed oil on the number of hippocampus cells and the serum
      antioxidant/oxidant status after cerebral ischemia and re-perfusion (CIR).
      Eighteen rats were divided into three equal groups. Group 1 served as the control
      group without CIR. Group 2 received poppy seed oil daily by oral gavage at a dose
      of 0.4 ml/kg, while group 3 was given 0.4 ml/kg saline solution by oral gavage
      per day; these treatments were continued for one month. Groups 2 and 3 were
      subjected to CIR induced by clamps on two points of both of the carotid arteries
      for 45 min followed by 45 min re-perfusion. There were significant decreases in
      the number of hippocampus cells between groups 1 and 2, and between groups 1 and
      3. The mean cell number in group 2 was not significantly different from that of
      group 3. The serum nitric oxide levels in CIR groups were elevated significantly
      compared to controls, and were significantly higher in group 2 than in group 3.
      The glutathione levels were increased significantly in the poppy seed oil treated
      group compared to the saline CIR groups. The malondialdehyde levels were markedly
      increased in group 3 compared to both groups 1 and 2. Our study suggests that
      poppy seed oil can improve antioxidant defense capacity after CIR, although this
      treatment did not alter significantly the frequency of cell death.

PMID- 22853040
TI  - An annotated bibliography of recent significant publications on indigo and
      related compounds.
AB  - This bibliography lists and provides commentary on publications describing the
      history, preparation, chemistry and applications of indigo and related dyes. The
      dates of the publications are mostly, but not exclusively, later than the
      previously published indigo bibliography. Note that commentary by the author is
      placed after the bibliographic information and is set in italics.

PMID- 22853041
TI  - Interleukin 1-beta upregulates brain-derived neurotrophic factor, neurotrophin 3
      and neuropilin 2 gene expression and NGF production in annulus cells.
AB  - The relationship between disc cells, nerves and pain production in the
      intervertebral disc is poorly understood. Neurotrophins, signaling molecules
      involved in the survival, differentiation and migration of neurons, and neurite
      outgrowth, are expressed in non-neuronal tissues including the disc. We
      hypothesized that three-dimensional exposure of human disc cells to the
      proinflammatory cytokine IL-1beta in vitro would elevate neurotrophin gene
      expression levels and production of nerve growth factor (NGF). Cells isolated
      from Thompson grade III and IV discs were cultured for 14 days under control
      conditions or with addition of 10(2) pM IL-1beta; mRNA was isolated and
      conditioned media assayed for NGF content. IL-1beta exposure in three-dimensional
      culture significantly increased expression of neurotrophin 3, brain-derived
      neurotrophic factor, and neuropilin 2 compared to controls. IL-1beta-exposed
      cells showed significantly increased NGF production compared to controls.
      Findings support our hypothesis, expand previous data concerning expression of
      neurotrophins, and provide the first documented expression of neurotrophin 3 and
      neuropilin 2. Our results have direct translational relevance, because they
      address the primary clinical issue of low back pain and open the possibility of
      novel analgesic therapies using specific small-molecular antagonists to
      neurotrophins.

PMID- 22853043
TI  - Knowledge of genetics and the role of the nurse in genetic health care: a survey
      of Italian nurses.
AB  - AIM: To report a study of Italian nurses' understanding of genetics. The
      objectives were to explore nurses' basic knowledge of genetics, their perceptions
      of the relevance of genetics and their opinions about the role of the genetic
      nurse. BACKGROUND: As the knowledge of the genetic basis for disease has
      developed, pressure to give genetic healthcare services for a larger number of
      individuals has increased. Specialist genetic nurses currently work in many
      countries; however, there are very few specialist genetic nurses in Italy and the
      preparedness of Italian nurses to give care for people with or at risk for
      genetic conditions is unclear. DESIGN: A cross-sectional survey. METHODS: The
      survey was administered over 3 months during 2011. Registered Nurses aged 21-65
      years were recruited via the website of the Italian nurse registration body,
      social network sites, hand-distributed flyers and email. Three hundred and eight
      five (90%) nurses completed the survey. Data were analysed using descriptive
      statistics, Kruskal-Wallis tests for distribution and Spearman's Rho analysis of
      correlations. RESULTS: The majority of respondents correctly answered at least
      four of five genetics knowledge questions. There were no statistically
      significant difference between knowledge scores when analysed according to age,
      but scores were positively correlated with higher academic qualifications and
      previous genetics education. A minority of respondents believed genetics was
      highly relevant to the nursing role. CONCLUSION: It is essential to ensure that
      educational provision for nurses includes not only the genetic concepts
      underpinning health and disease, but also how these are applied to nursing care.

PMID- 22853044
TI  - Engagement of non-government organisations and community care workers in
      collaborative TB/HIV activities including prevention of mother to child
      transmission in South Africa: opportunities and challenges.
AB  - BACKGROUND: The implementation of collaborative TB/HIV activities may help to
      mitigate the impact of the dual epidemic on patients and communities. Such
      implementation requires integrated interventions across facilities and levels of
      government, and with communities. Engaging Community Care Workers (CCWs) in the
      delivery of integrated TB/HIV services may enhance universal coverage and
      treatment outcomes, and address human resource needs in sub-Saharan Africa.
      METHODS: Using pre-intervention research in Sisonke district, KwaZulu-Natal,
      South Africa as a case study, we report on three study objectives: (1) to
      determine the extent of the engagement of NGOs and CCWs in the implementation of
      collaborative TB/HIV including PMTCT; (2) to identify constraints related to
      provision of TB/HIV/PMTCT integrated care at community level; and (3) to explore
      ways of enhancing the engagement of CCWs to provide integrated TB/HIV/PMTCT
      services. Our mixed method study included facility and NGO audits, a household
      survey (n = 3867), 33 key informant interviews with provincial, district,
      facility, and NGO managers, and six CCW and patient focus group discussions.
      RESULTS: Most contracted NGOs were providing TB or HIV support and care with
      little support for PMTCT. Only 11% of facilities' TB and HIV patients needing
      care and support at the community level were receiving support from CCWs. Only 2%
      of pregnant women reported being counseled by CCWs on infant feeding options and
      HIV testing. Most facilities (83%) did not have any structural linkage with NGOs.
      Major constraints identified were system-related: structural, organizational and
      managerial constraints; inadequate CCW training and supervision; limited scope of
      CCW practice; inadequate funding; and inconsistency in supplies and equipment.
      Individual and community factors, such as lack of disclosure, stigma related to
      HIV, and cultural beliefs were also identified as constraints. CONCLUSIONS:
      NGO/CCW engagement in the implementation of collaborative TB/HIV/PMTCT activities
      is sub-optimal, despite its potential benefits. Effective interventions that
      address contextual and health systems challenges are required. These should
      combine systematic skills-building, an enhanced scope of practice and consistent
      CCW supervision with a reliable referral and monitoring and evaluation system.

PMID- 22853045
TI  - Velocity and acceleration before contact in the tackle during rugby union
      matches.
AB  - The velocity and acceleration at which the ball-carrier or tackler enters the
      tackle may contribute to winning the contest and prevailing injury free. Velocity
      and acceleration have been quantified in controlled settings, whereas in match
      play it has been subjectively described. The purpose of this study was to
      determine the velocity and acceleration of the ball-carrier and tackler before
      contact during match-play in three competitions (Super 14, Varsity Cup, and Under
      19 Currie Cup). Using a two-dimensional scaled version of the field, the velocity
      and acceleration of the ball-carrier and tackler were measured at every 0.1 s to
      contact for 0.5 s. For front-on tackles, a significant difference (P < 0.05)
      between the ball-carrier (4.6 +/- 1 m . s-1) and tackler (7.1 +/- 3.5 m . s-1)
      was found at the 0.5 s time to contact interval in the Varsity Cup. For side-on
      tackles, differences between the two opposing players were found at 0.5 s (ball
      carrier: 4.6 +/- 1.7 m . s-1; tackler: 3.1 +/- 1.2 m . s-1) and 0.4 s (ball
      carrier: 6.3 +/- 2.3 m . s-1; tackler: 3.7 +/- 1.6 m . s-1) at Under-19 level.
      After 0.4 s, no significant differences (P > 0.05) were evident. Also, the ball
      carrier's velocity over the 0.5 s was relatively stable compared with that of the
      tackler. Results suggest that tacklers adjust their velocity to reach a suitable
      relative velocity before making contact with the ball-carrier.

PMID- 22853046
TI  - Insulin-like growth factor system in Egyptian children with acute lymphoblastic
      leukemia.
AB  - Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been
      reported to play an important role in tumor proliferation. This study aimed to
      investigate the validity of measuring IGFs and specific IGFBPs in the serum of
      Egyptian children with acute lymphoblastic leukemia (ALL) as additional markers
      in diagnosis and follow-up of the disease. IGF-I, IGF-II, IGFBP-2, and IGFBP-3
      were determined in the sera of 33 ALL patients at time of diagnosis and after an
      intensification phase of chemotherapy (IPC) that lasts about 6 months as well as
      in 15 healthy children as a control group using enzyme-linked immunosorbent assay
      (ELISA) technique. At time of diagnosis, serum IGF-I, IGF-II, and IGFBP-3 were
      significantly lower than those in the control group. After IPC, serum IGF-I and
      IGF-II returned to their normal levels, while serum IGFBP-3 was still decreased.
      On the other hand, serum IGFBP-2 was significantly higher than those in the
      control group at diagnosis, but returned to normal value after IPC. In
      conclusion, the changes in IGF system could be useful to support diagnosis and
      follow-up of children with ALL.

PMID- 22853047
TI  - Using "warm handoffs" to link hospitalized smokers with tobacco treatment after
      discharge: study protocol of a randomized controlled trial.
AB  - BACKGROUND: Post-discharge support is a key component of effective treatment for
      hospitalized smokers, but few hospitals provide it. Many hospitals and care
      settings fax-refer smokers to quitlines for follow-up; however, less than half of
      fax-referred smokers are successfully contacted and enrolled in quitline
      services. "Warm handoff" is a novel approach to care transitions in which health
      care providers directly link patients with substance abuse problems with
      specialists, using face-to-face or phone transfer. Warm handoff achieves very
      high rates of treatment enrollment for these vulnerable groups. METHODS: The aim
      of this study-"EQUIP" (Enhancing Quitline Utilization among In-Patients)-is to
      determine the effectiveness, and cost-effectiveness, of warm handoff versus fax
      referral for linking hospitalized smokers with tobacco quitlines. This study
      employs a two-arm, individually randomized design. It is set in two large Kansas
      hospitals that have dedicated tobacco treatment interventionists on staff. At
      each site, smokers who wish to remain abstinent after discharge will be randomly
      assigned to groups. For patients in the fax group, staff will provide standard in
      hospital intervention and will fax-refer patients to the state tobacco quitline
      for counseling post-discharge. For patients in the warm handoff group, staff will
      provide brief in-hospital intervention and immediate warm handoff: staff will
      call the state quitline, notify them that a warm handoff inpatient from Kansas is
      on the line, then transfer the call to the patients' mobile or bedside hospital
      phone for quitline enrollment and an initial counseling session. Following the
      quitline session, hospital staff provides a brief check-back visit. Outcome
      measures will be assessed at 1, 6, and 12 months post enrollment. Costs are
      measured to support cost-effectiveness analyses. We hypothesize that warm
      handoff, compared to fax referral, will improve care transitions for tobacco
      treatment, enroll more participants in quitline services, and lead to higher quit
      rates. We also hypothesize that warm handoff will be more cost-effective from a
      societal perspective. DISCUSSION: If successful, this project offers a low-cost
      solution for more efficiently linking millions of hospitalized smokers with
      effective outpatient treatment-smokers that might otherwise be lost in the
      transition to outpatient care. TRIAL REGISTRATION: Clinical Trials Registration
      NCT01305928.

PMID- 22853050
TI  - The importance of who infects whom: the evolution of diversity in host resistance
      to infectious disease.
AB  - Variation for resistance to infectious disease is ubiquitous and critical to host
      and parasite evolution and to disease impact, spread and control. However, the
      processes that generate and maintain this diversity are not understood. We
      examine how ecological feedbacks generate diversity in host defence focussing on
      when polymorphism can evolve without co-evolution of the parasite. Our key result
      is that when there is heritable variation in hosts in both their transmissibility
      and susceptibility along with costs to resistance, there is the possibility of
      the evolution of polymorphism. We argue that a wide range of behavioural or
      physiological mechanisms may lead to relationships between transmissibility and
      susceptibility that generate diversity. We illustrate this by showing that a
      tendency for higher contacts between related individuals leads to polymorphism.
      Only dimorphisms can evolve when infection is determined only by an individuals'
      susceptibility or when transmissibility and susceptibility are simply positively
      or negatively correlated.

PMID- 22853049
TI  - Conspicuity of breast lesions at different b values on diffusion-weighted
      imaging.
AB  - BACKGROUND: Diffusion-weighted (DW) imaging has shown potential to differentiate
      between malignant and benign breast lesions. However, different b values have
      been used with varied sensitivity and specificity. This study aims to
      prospectively evaluate the influence of b value on the detection and assessment
      of breast lesions. METHODS: Institutional review board approval and informed
      patient consent were obtained. Between February 2010 and September 2010, sixty
      women suspected of having breast cancer by clinical examination and mammography
      underwent bilateral breast MRI and DW imaging (with maximum b values of 600, 800,
      and 1000 s/mm(2)). Conspicuity grades of lesions at different b values on DW
      images were performed. Signal intensity and apparent diffusion coefficient (ADC)
      values were recorded and compared among different b values by the signal-to-noise
      ratio (SNR), contrast-to-noise ratio (CNR) and receiver operating characteristic
      (ROC) curve. RESULTS: Fifty-seven lesions from 52 recruited patients including
      39/57 (68%) malignant and 18/57 (32%) benign were confirmed with pathology. DCE
      MRI accurately detected 53 lesions with the sensitivity of 93.0% and specificity
      of 66.7%, and DW imaging accurately detected 51 lesions with the sensitivity of
      89.5% and specificity of 100%. There were no significant differences in
      conspicuity grades compared among the three b values (P = 0.072), although the
      SNR and CNR of breast lesions decreased significantly with higher b values. Mean
      ADCs of malignant lesions (b = 600 s/mm(2), 1.07 +/- 0.26 * 10-3 mm(2)/s; b = 800
      s/mm(2), 0.96 +/- 0.22 * 10-3 mm(2)/s; b = 1000 s/mm(2), 0.92 +/- 0.26 * 10-3
      mm(2)/s) were significantly lower than those of benign lesions (b = 600 s/mm(2),
      1.55 +/- 0.40 * 10-3 mm(2)/s; b = 800 s/mm(2), 1.43 +/- 0.38 * 10-3 mm(2)/s; b =
      1000 s/mm(2), 1.49 +/- 0.38 * 10-3 mm(2)/s) with all P values <0.001, but there
      were no significant differences among the three b values (P = 0.303 and 0.840 for
      malignant and benign lesions, respectively). According to the area under the ROC
      curves, which were derived from ADC and differentiate malignant from benign
      lesions, no significant differences were found among the three b values (P =
      0.743). CONCLUSIONS: DW imaging is a potential adjunct to conventional MRI in the
      differentiation between malignant and benign breast lesions. Varying the maximum
      b value from 600 to 1000 s/mm(2) does not influence the conspicuity of breast
      lesions on DW imaging at 1.5 T.

PMID- 22853048
TI  - Outcome of therapy-related myeloid neoplasms treated with azacitidine.
AB  - BACKGROUND: Therapy-related myeloid neoplasms (t-MN), including myelodysplastic
      syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical
      and biologic unfavorable prognostic features, including high levels of DNA
      methylation. METHODS: We retrospectively evaluated 50 t-MN patients (34 MDS and
      16 AML) selected among all patients receiving azacitidine (AZA) at 10 Italian
      Hematology Centers. Patients had developed a t-MN at a median of 6.5 years (range
      1.7- 29) after treatment of the primary tumor (hematological neoplasm, 27
      patients; solid tumor, 23 patients). RESULTS: The overall response rate was 42%
      (complete remission: 10 patients, partial remission: 2 and hematological
      improvement: 8 patients) and was obtained after a median of 3 cycles (range 1-6).
      Median overall survival (OS) was 21 months (range 1-53.6+) from AZA start. OS was
      significantly better in patients with less than 20% blasts, in normal karyotype t
      AML and when AZA was used as front-line treatment. This was confirmed by the
      multivariate analysis. CONCLUSIONS: This study reports efficacy of AZA in the
      largest series of therapy-related MN patients treated with 5-AZA. Our data show
      that blasts and karyotype maintain their important prognostic role in t-MN also
      in the azacitidine era.

PMID- 22853051
TI  - End-of-life practices in Danish ICUs: development and validation of a
      questionnaire.
AB  - BACKGROUND: Practices for withholding or withdrawing therapy vary according to
      professional, cultural and religious differences. No Danish-validated
      questionnaire examining withholding and withdrawing practices exists, thus the
      aim of this study was to develop and validate a questionnaire for surveying the
      views of intensive care nurses, intensivists, and primary physicians regarding
      collaboration and other aspects of withholding and withdrawing therapy in the
      ICU. METHODS: A questionnaire was developed on the basis of literature, focus
      group interviews with intensive care nurses and intensivists, and individual
      interviews with primary physicians. The questionnaire was validated in the
      following 3 phases: a qualitative test with 17 participants; a quantitative pilot
      test with 60 participants; and a survey with 776 participants. The validation
      process included tests for face and content validity (by interviewing
      participants in the qualitative part of the pilot study), reliability (by
      assessing the distribution of responses within the individual response
      categories), agreement (by conducting a test-retest, evaluated by paired
      analyses), known groups' validity (as a surrogate test for responsiveness, by
      comparing two ICUs with a known difference in end-of-life practices), floor and
      ceiling effect, and missing data. RESULTS: Face and content validity were
      assessed as good by the participants in the qualitative pilot test; all
      considered the questions relevant and none of the participants found areas
      lacking. Almost all response categories were used by the participants, thus
      demonstrating the questionnaires ability to distinguish between different
      respondents, agreement was fair (the average test-retest agreement for the Likert
      scale responses was 0.54 (weighted kappa; range, 0.25-0.73), and known groups'
      validity was proved by finding significant differences in level of satisfaction
      with interdisciplinary collaboration and in experiences of withdrawal decisions
      being unnecessarily postponed. Floor and ceiling effect was in accordance with
      other questionnaires, and missing data was limited to a range of 0-7% for all
      questions. CONCLUSIONS: The validation showed good and fair areas of validity of
      the questionnaire. The questionnaire is considered a useful tool to assess the
      perceptions of collaboration and other aspects of withholding and withdrawing
      therapy practices in Danish ICUs amongst nurses, intensivists, and primary
      physicians.

PMID- 22853173
TI  - Sexually transmitted infections associated syndromes assisted in the primary
      health care in Northeast, Brazil.
AB  - BACKGROUND: The lack of information on the care for sexually transmitted
      infections (STI) associated syndromes may contribute for its non-inclusion as
      prevention and control strategy for STI in Brazil. This study aims to analyze the
      cases of STI - Associated Syndromes assisted in primary health care center in a
      city in Northeast Brazil associating them with socio-demographic and behavioral
      variables. METHODS: This is a retrospective study that analyzed 5148 consultation
      forms and medical records of patients assisted in a primary health care center
      who presented at least one genital syndrome from 1999 to 2008. Was considered as
      dependent variables the genital syndromes and serologies for syphilis and HIV and
      as independent variables the socio-demographic and behavioral aspects. It was
      used Pearson's chi-square test to analyze the differences between the categorical
      variables, with a significance level of 5%. It was performed a multivariate
      analysis through the multivariate logistic regression model with the variables
      with p <0.05. We used odds ratio with a confidence interval of 95%. RESULTS: The
      most frequent syndromes were vaginal discharge and/or cervicitis (44%) and
      genital wart (42.2%). Most people were between 20 and 39 years old (70%) and
      women (74.2%). Genital ulcer was most prevalent among men (OR = 2.67; CI 95% 1.99
      3.58) and people who studied more than eight years (OR = 1.33; CI 95% 1.00-1.75)
      and wart prevailed among men (OR = 3.92; IC 95% 3.36-4.57), people under 29 years
      old (OR = 1.81; CI 95% 1.59-2.07) and who studied more than eight years (OR =
      1.75; CI 95% 1.54-1.99). The Venereal Disease Research Laboratory (VDRL) was
      positive in 7.3% of men and in 7.1% of women and the Anti-HIV in 3.1% of men and
      0.7% of women. CONCLUSION: Vaginal discharge was the most frequent syndrome
      assisted in primary health care, followed by genital wart. The high prevalence of
      genital wart justifies the greater effort for the proper follow-up of these
      cases. Men presented more genital wart and ulcer and reported having more sexual
      partners, showing their need for a greater access and inclusion in health
      activities developed in primary health care in Brazil.

PMID- 22853175
TI  - Heavy metals health risk assessment for population via consumption of food crops
      and fruits in Owerri, South Eastern, Nigeria.
AB  - BACKGROUND: This study assessed lead, cadmium, and nickel level in food crops,
      fruits and soil samples from Ohaji and Umuagwo and Owerri in South Eastern
      Nigeria and estimated the potential health risks of metals. Samples were washed,
      oven-dried at 70-80 degrees C for 24 h and powdered. Samples were digested with
      perchloric acid and nitric acid. Metals were analysed with Unicam Atomic
      Absorption Spectrophotometer. RESULT: The concentration of Pb, Cd, and Ni in
      Ohaji exceeded the maximum allowable concentrations for agricultural soil as
      recommended by EU. Lead, Cd, and Ni in the food crops were highest in Oryza
      sativa, Glycine max, and Pentabacta microfila respectively. Highest levels of Pb,
      Cd, and Ni, in fruits were detected in Canarium schweinfurthii, Citrus
      reticulata, Ananas comosus respectively. The true lead and cadmium intake for the
      rice based meal were 3.53 and 0.034 g/kg respectively. Whereas the true intake of
      lead and cadmium for the cassava based meal were 19.42 and 0.049 g/kg
      respectively. CONCLUSION: Local food stuff commonly available in South Eastern
      Nigeria villages may contribute to the body burden of heavy metal. This is of
      public health importance.

PMID- 22853176
TI  - Editorial comment to robot-assisted or pure laparoscopic nerve-sparing radical
      prostatectomy: what is the optimal procedure for the surgical margins? A single
      center experience.

PMID- 22853174
TI  - Thermally induced protein unfolding probed by isotope-edited IR spectroscopy.
AB  - Infrared (IR) spectroscopy has been widely utilized for the study of protein
      folding, unfolding, and misfolding processes. We have previously developed a
      theoretical method for calculating IR spectra of proteins in the amide I region.
      In this work, we apply this method, in combination with replica-exchange
      molecular dynamics simulations, to study the equilibrium thermal unfolding
      transition of the villin headpiece subdomain (HP36). Temperature-dependent IR
      spectra and spectral densities are calculated. The spectral densities correctly
      reflect the unfolding conformational changes in the simulation. With the help of
      isotope labeling, we are able to capture the feature that helix 2 of HP36 loses
      its secondary structure before global unfolding occurs, in agreement with
      experiment.

PMID- 22853178
TI  - LGBT health research: introduction to the special issue.

PMID- 22853177
TI  - Validity and reliability of a physical activity questionnaire for Vietnamese
      adolescents.
AB  - BACKGROUND: Accurate assessment of physical activity in adolescents at population
      level is necessary. In Vietnam, the International Physical Activity Questionnaire
      (IPAQ) and Physical Activity Questionnaire for Adolescents (PAQA) have been
      validated against accelerometers for use in adolescents. However, these
      questionnaires were originally designed for adults and showed poor validity. This
      study aims to assess the reliability and validity of the Vietnamese Adolescent
      Physical Activity Recall Questionnaire (V-APARQ). METHODS: One hundred and sixty
      five students were recruited from four junior high schools in Ho Chi Minh City
      Vietnam in 2004. V-APARQ asked students to report their usual organised and non
      organised physical activity during a normal week and moderate- (MPA), vigorous-
      (VPA and moderate-to-vigorous- (MVPA) physical activity were calculated.
      Reliability was assessed by test-retest (2 weeks apart). Construct validity was
      assess by 7-day accelerometry, following the completion of the first V-APARQ.
      RESULTS: The construct validity of the V-APARQ showed Spearman correlation of
      0.25 and 0.22 for the assessment of the questionnaire when compared to the
      accelerometer. Test-retest reliability showed a weighted Kappa of 0.75 and the
      intra-class correlation coefficient for MVPA was 0.57 for the whole group (MPA
      =0.37 and VPA = 0.62), and were higher in boys than girls. The Bland-Altman plots
      for reliability show a mean difference of 0.4 minutes (95 % CI = -3.2, 4.0) for
      daily MVPA (n = 146) and the limits of agreement were -42.6 to 43.4 mins/day. In
      boys MVPA was lower on the first, compared with second administration of V-APARQ
      while the reverse was observed among girls. CONCLUSION: The reliability and
      validity of the V-APARQ were low to fair, but are comparable to other self-report
      physical activity questionnaires used among adolescents. V-APARQ will be useful
      for population monitoring of change in physical activity among urban Vietnamese
      adolescents.

PMID- 22853179
TI  - Qualitative analysis in gay men's health research: comparing thematic, critical
      discourse, and conversation analysis.
AB  - Gay men's health typically relies on traditional forms of qualitative analysis,
      such as thematic analysis, and would benefit from a diversity of analytic
      approaches. Such diversity offers public health researchers a breadth of tools to
      address different kinds of research questions and, thus, substantiate different
      types of social phenomenon relevant to the health and wellbeing of gay men. In
      this article, I compare and contrast three qualitative analytic approaches:
      thematic, critical discourse, and conversation analysis. I demonstrate and
      distinguish their key analytic assumptions by applying each approach to a single
      data excerpt taken from a public health interview conducted for a broader study
      on gay men's health. I engage in a discussion of each approach in relation to
      three themes: its utility for gay men's health, its approach to dilemmas of
      voice, and its capacity for reflexivity. I advocate that qualitative researchers
      should capitalise on the full range of qualitative analytic approaches to achieve
      the goals of gay men's health. However, I specifically encourage qualitative
      researchers to engage with conversation analysis, not only because of its
      capacity to resolve dilemmas of voice and to achieve reflexivity, but also for
      its ability to capture forms of social life hitherto undocumented through
      thematic and critical discourse analysis.

PMID- 22853180
TI  - Reported excellent health among men in same-sex and mixed-sex couples: Behavioral
      Risk Factor Surveillance System, 1993-2010.
AB  - Self-reported excellent health was examined across sexual orientation among male
      adult couples using 18 years of data from the Behavioral Risk Factor Surveillance
      System. Men in same-sex couples were more likely to report being in excellent
      health (28.7%) than men in unmarried and married mixed-sex couples (20.4% and
      23.2%). After adjusting for other demographic and health factors, men in same-sex
      couples remained more likely to report excellent health than men in unmarried
      mixed-sex couples, but not than men in married mixed-sex couples. Reporting only
      adverse health disparities provides a partial picture of sexual minority health,
      and discounts the role of resilience and other health promoting factors in these
      populations.

PMID- 22853181
TI  - Seeking safer sexual spaces: queer and trans young people labeled with
      intellectual disabilities and the paradoxical risks of restriction.
AB  - Young lesbian, gay, bisexual, and transgender (LGBT) people labeled with
      intellectual disabilities have unique sexual health needs that are not being met.
      Denial by others of their right to pleasure and the exercise of heightened
      external control over their sexuality are commonplace. Current research indicates
      that these youth are at heightened risk for compromised sexual health. This study
      aimed to explore the ways in which social and environmental conditions influence
      vulnerability to adverse sexual health outcomes for this population. We used a
      community-based research approach to conduct qualitative interviews and focus
      groups with 10 young LGBT people (aged 17-26) labeled with intellectual
      disabilities. Participants reported multiple limitations on their autonomy that
      resulted in having sex in places where they did not feel comfortable and were
      unlikely to practice safer sex. Attempts by authority figures to protect youth
      through limits on their autonomy may be unintentionally leading to negative
      sexual health outcomes.

PMID- 22853182
TI  - Correlates of wellbeing among African American lesbians.
AB  - Although there is a growing body of knowledge about health among African American
      women in general, there is a dearth of information on African American lesbians.
      The primary purpose of this study was to investigate the correlates of health
      related quality of life among African American lesbians using a cross-sectional
      anonymous survey with topics and measures developed by members of the African
      American lesbian community. Surveys were completed by 123 English speaking adult
      women who identified as African American lesbians and were attending the Zuna
      Institute's National Black Lesbian Conference. Overall, we found a very high
      health-related quality of life, in spite of a high frequency of health
      impairments. The average body mass index (BMI) for this sample was 32.2 (SD =
      8.0); 13% were morbidly obese, having a BMI of 40 or more and only 15% of the
      women were in a healthy weight range; advancing age was associated with poorer
      physical functioning, decreased physical role functioning, and more pain. Health
      related quality of life was associated with depression and spirituality, but not
      religion. This study highlights the need for subjective measures of health
      related quality of life as well as checklists of diseases and disorders.

PMID- 22853183
TI  - Health care access and perceptions of provider care among individuals in same-sex
      couples: findings from the Medical Expenditure Panel Survey (MEPS).
AB  - We compared individuals in same-sex couples to those in different-sex married
      couples on various health care indicators using the Medical Expenditure Panel
      Survey. Compared to individuals in different-sex married couples, individuals in
      same-sex couples were more likely to report difficulty seeing specialists,
      getting medical care when needed, and delays getting necessary prescription
      drugs. They were also more likely to report dissatisfaction with the level of
      respect shown by and time spent with providers. This study suggests that
      individuals in same-sex couples are more likely to face barriers to care and that
      individuals in same-sex couples have less positive perceptions of provider
      interactions.

PMID- 22853184
TI  - Lesbians' and bisexual women's definition of health.
AB  - Health is an abstract term used to describe the state of the human body, a mental
      state or the likelihood of longevity. Throughout history, many definitions have
      been provided by agencies and healthcare professionals. Although the meaning of
      health has a long and well-examined history, there remains a gap in the
      literature surrounding the meaning of health to specific populations of people.
      The purpose of this article is to present an analysis of the meaning of health
      from the perspective of lesbians and bisexual women. A content analysis was
      performed on the definition of health as reported by 189 sexual minority women.
      The conclusions from this study strongly suggest that health interventions for
      lesbian and bisexual women focus on what women want to achieve, rather than on
      what individual behavior should be.

PMID- 22853185
TI  - The last drag: an evaluation of an LGBT-specific smoking intervention.
AB  - Many studies in the past 20 years have documented that lesbian, gay, bisexual,
      and transgender (LGBT) individuals smoke at rates that exceed the general
      population, yet, there have been few reports of smoking cessation interventions
      targeting this population. This study reports on data from 233 participants in
      The Last Drag, a seven-session, six-week group education and support intervention
      tailored for LGBT smokers. Data on smoking rates were collected during the first
      and last sessions, and at one, three, and six months post-intervention. As with
      many interventions over time, missing data is a challenge in determining success
      rates, but even using the most conservative estimates, nearly 60% were smoke-free
      at the end of the intervention, and 36% remained smoke-free by six months post
      intervention. This success rate is comparable to, or better, than many mainstream
      smoking cessation interventions reported in the literature. The Last Drag is an
      effective, low-cost, LGBT-specific community intervention that can be replicated
      in other communities.

PMID- 22853186
TI  - LyP-1 modification to enhance delivery of artemisinin or fluorescent probe loaded
      polymeric micelles to highly metastatic tumor and its lymphatics.
AB  - Metastatic cancers are prone to form metastasis at a distance and acquire drug
      resistance, which are very common clinically and major obstacles to successful
      chemotherapy. Besides the tumor itself, the lymphatic system is increasingly
      emerging as a new target for anticancer therapy because it is an important route
      of tumor metastasis. To specifically deliver drug to both highly metastatic tumor
      and its lymphatics, tumor- and tumor lymphatics-homing peptide (LyP-1) conjugated
      PEG-PCL micelles (LyP-1-PM) were first constructed. Artemisinin (ART), a natural
      product with potential anticancer and antilymphangiogenesis effects, was chosen
      as the model drug and associated into the micelles. Both PM and LyP-1-PM had
      similar physiochemical properties, about 30 nm in size with uniform distribution.
      Highly metastatic breast cancer MDA-MB-435S cells and lymphatic endothelial cells
      (LEC) were applied as cell models. Flow cytometry and confocal microscopy studies
      showed that LyP-1-PM exhibited its specificity to both cell lines evidenced by
      its higher cellular uptake than PM. LyP-1-PM-ART demonstrated higher inhibition
      effect than PM-ART against these two cell lines in cell apoptosis, cell cycle and
      cytotoxicity tests. Near-infrared imaging showed that LyP-1-PM was distributed
      more in orthotopic MDA-MB-435S tumor than PM. Further study by colocalization
      indicated that PM accumulated near blood vessels, while LyP-1-PM further homed to
      tumor lymphatic vessels. LyP-1-PM achieved higher antitumor efficacy than other
      ART formulations in vivo with low toxicity. Both in vitro and in vivo studies
      here proved that LyP-1 modification enhanced the specific delivery of ART or
      fluorescent probe loaded polymeric micelles to MDA-MB-435S and LEC. Therefore,
      LyP-1-PM might be promising in terms of specific delivery of therapeutic or
      imaging agents to both highly metastatic breast tumor and its lymphatics.

PMID- 22853188
TI  - Thermochemistry of Sr2Ce(1-x)Pr(x)O4 (x = 0, 0.2, 0.5, 0.8, and 1): variable
      temperature and -atmosphere in-situ and ex-situ powder X-ray diffraction studies
      and their physical properties.
AB  - A novel family of metal oxides with a chemical formula of Sr(2)Ce(1-x)Pr(x)O(4)
      (x = 0, 0.2, 0.5, 0.8, and 1) was developed as mixed oxide ion and electronic
      conductors for solid oxide fuel cells (SOFCs). All of the investigated samples
      were synthesized by the ceramic method at 1000  degrees C in air and 
      characterized by powder X-ray diffraction (PXRD), selected area electron
      diffraction (SAED), thermogravimetric analysis (TGA), scanning electron
      microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and electrochemical
      impedance spectroscopy (EIS). Ex-situ PXRD reveals that the Sr(2)PbO(4)-type
      Sr(2)CeO(4) decomposes readily into a mixture of perovskite-type SrCeO(3) and
      rock-salt-type SrO at 1400  degrees C in air. Surprisingly, the decomposed
      products are converted back to the original Sr(2)PbO(4)-type Sr(2)CeO(4) phase at
      800  degrees C in air, as confirmed by in-situ PXRD. Thermal decomposition is
      highly suppressed in Sr(2)Ce(1-x)Pr(x)O(4) compounds for Pr > 0, suggesting that
      Pr improves the thermal stability of the compounds. Rietveld analysis of PXRD and
      SAED supported that both Pr and Ce ions are located on the 2a site in Pbam (space
      group no. 55). The electrical transport mechanism could be correlated to the
      reduction of Pr and/or Ce ions and  subsequent loss of oxide ions at elevated
      temperatures, as shown by TGA and in-situ PXRD. Conductivity increases with Pr
      content in Sr(2)Ce(1-x)Pr(x)O(4). The highest total conductivity of 1.24 * 10(-1)
      S cm(-1) was observed for Sr(2)Ce(0.2)Pr(0.8)O(4) at 663  degrees C in air.

PMID- 22853189
TI  - Special series on positive behaviour support--efficacy: introduction.

PMID- 22853187
TI  - Regulation of aortic extracellular matrix synthesis via noradrenergic system and
      angiotensin II in juvenile rats.
AB  - CONTEXT: Extracellular matrix (ECM) synthesis regulation by sympathetic nervous
      system (SNS) or angiotensin II (ANG II) was widely reported, but interaction
      between the two systems on ECM synthesis needs further investigation. OBJECTIVE:
      We tested implication of SNS and ANG II on ECM synthesis in juvenile rat aorta.
      MATERIALS AND METHODS: Sympathectomy with guanethidine (50 mg/kg, subcutaneous)
      and blockade of the ANG II AT1 receptors (AT1R) blocker with losartan (20
      mg/kg/day in drinking water) were performed alone or in combination in rats. mRNA
      and protein synthesis of collagen and elastin were examined by Q-RT-PCR and
      immunoblotting. RESULTS: Collagen type I and III mRNA were increased respectively
      by 62 and 43% after sympathectomy and decreased respectively by 31 and 60% after
      AT1R blockade. Combined treatment increased collagen type III by 36% but not
      collagen type I. The same tendency of collagen expression was observed at mRNA
      and protein levels after the three treatments. mRNA and protein level of elastin
      was decreased respectively by 63 and 39% and increased by 158 and 15% after
      losartan treatment. Combined treatment abrogates changes induced by single
      treatments. DISCUSSION AND CONCLUSION: The two systems act as antagonists on ECM
      expression in the aorta and combined inhibition of the two systems prevents
      imbalance of mRNA and protein level of collagen I and elastin induced by single
      treatment. Combined inhibition of the two systems prevents deposit or excessive
      reduction of ECM and can more prevent cardiovascular disorders.

PMID- 22853190
TI  - Metal-free, NHPI catalyzed oxidative cleavage of C-C double bond using molecular
      oxygen as oxidant.
AB  - A metal-free N-hydroxyphthalimide (NHPI) catalyzed aerobic oxidative cleavage of
      olefins has been developed. Molecular oxygen is used as the oxidant and reagent
      for this oxygenation reaction. This methodology has prevented the use of toxic
      metals or overstoichiometric amounts of traditional oxidants, showing good
      economical and environmental advantages. Based on the experimental observations,
      a plausible mechanism is proposed.

PMID- 22853192
TI  - Highly enhanced acetone sensing performances of porous and single crystalline ZnO
      nanosheets: high percentage of exposed (100) facets working together with surface
      modification with Pd nanoparticles.
AB  - Porous and single crystalline ZnO nanosheets, which were synthesized by annealing
      hydrozincite Zn(5)(CO(3))(2)(OH)(6) nanoplates produced with a water/ethylene
      glycol solvothermal method, are used as building blocks to construct functional
      Pd-ZnO nanoarchitectures together with Pd nanoparticles based on a self-assembly
      approach. Chemical sensing performances of the ZnO nanosheets were investigated
      carefully before and after their surface modification with Pd nanoparticles. It
      was found that the chemical sensors made with porous ZnO nanosheets exhibit high
      selectivity and quick response for detecting acetone, because of the 2D ZnO
      nanocrystals exposed in (100) facets at high percentage. The performances of the
      acetone sensors can be further improved dramatically, after the surfaces of ZnO
      nanosheets are modified with Pd nanoparticles. Novel acetone sensors with
      enhanced response, selectivity and stability have been fabricated successfully by
      using nanoarchitectures consisting of ZnO nanosheets and Pd nanoparticles.

PMID- 22853191
TI  - Water-soluble poly(L-serine)s with elongated and charged side-chains: synthesis,
      conformations, and cell-penetrating properties.
AB  - Water-soluble poly(L-serine)s bearing long side-chain with terminal charge groups
      were synthesized via ring-opening polymerization of O-pentenyl-L-serine N
      carboxyanhydride followed by thiol-ene reactions. These side-chain modified
      poly(L-serine)s adopt beta-sheet conformation in aqueous solution with excellent
      stability against changes in pH and temperature. These water-soluble poly(L
      serine) derivatives with charged side-chain functional groups and stable beta
      sheet conformations showed membrane-penetrating capabilities in different cell
      lines with low cytotoxicity.

PMID- 22853193
TI  - Individual, situational and lifestyle factors related to shift work tolerance
      among nurses who are new to and experienced in night work.
AB  - AIM: To identify individual, situational and lifestyle variables related to shift
      work tolerance among nurses who have worked night shifts for less than 1 year and
      nurses who have worked night shift for more than 6 years, all engaged in rotating
      shift work. BACKGROUND: Working shifts is related to negative health
      consequences. Factors related to shift work tolerance may differ between nurses
      with little experience and nurses with extensive experience in night work.
      DESIGN: Cross-sectional questionnaire study. METHODS: A questionnaire including
      established instruments measuring shift work tolerance, personality, work
      schedule and lifestyle factors was administered between November 2008-May 2010.
      Randomly selected Norwegian nurses (n = 749) participated in the study; 322 were
      new and 427 were experienced in night work. RESULTS: There were no statistically
      significant differences in shift work tolerance between the new to night work
      nurses and the nurses who were experienced in night work. Young age was related
      to higher shift work tolerance. Hardiness was positively related to shift work
      tolerance in both groups. For the new to night work nurses, morningness was
      positively related to shift work tolerance. For the experienced in night work
      nurses, languidity, work hours per week and caffeine consumption were negatively,
      but flexibility was positively, related to shift work tolerance. CONCLUSION:
      Several variables were related to shift work tolerance among rotating shift
      working nurses, especially hardiness. Somewhat different variables were related
      to shift work tolerance for nurses who were new to night work than for nurses
      with more experience in night work.

PMID- 22853194
TI  - The influence of gender on the injury severity, course and outcome of traumatic
      brain injury.
AB  - OBJECTIVE: To examine the independent association of gender with injury severity,
      clinical course, pituitary dysfunction and outcome after traumatic brain injury
      (TBI). DESIGN: Prospective cohort, analysis of a data sub-set collected as part
      of the nation-wide database 'The Structured Data Assessment of Hypopituitarism
      after TBI and SAH'. METHODS AND PROCEDURES: Four hundred and twenty-seven
      patients following TBI were observed from acute care through neurological
      rehabilitation. Outcome was measured by Glasgow Outcome Scale (GOS), employment
      status and living situation post-injury. As a secondary outcome measure anterior
      pituitary function was assessed. RESULTS: There were no differences in injury
      severity between men and women. Age had a significant effect on the GCS score (p
      = 0.0295), but gender did not (p = 0.4105). The outcome was equivalent between
      men and women once corrected for age. Logistic regression revealed that gender
      had no effect (p = 0.8008), but age (p = 0.0021) and initial injury severity (p =
      0.0010) had an effect on the GOS. After correcting for pre-injury living
      situation and employment only initial injury severity (p = 0.0005) influenced
      GOS. Pituitary insufficiency was not affected by sex or age. CONCLUSION: Gender
      does not seem to influence the course and outcome of TBI. Outcome parameters were
      affected foremost by initial injury severity and by age, but not by sex.

PMID- 22853196
TI  - Intraindividual long term stability and response corridors of cytokines in
      healthy volunteers detected by a standardized whole-blood culture system for bed
      side application.
AB  - BACKGROUND: The variation of immune cell activities over time is an immanent
      property of the human immune system, as can be measured by the stimulated
      secretion of cytokines in cell cultures. However, inter-individual variability is
      considerably higher. Especially the latter is the major reason why it has not
      been possible to establish international standard values for cytokines as was
      possible for other parameters, such as leukocyte sub-population numbers. In this
      trial, a highly standardized whole-blood culture model (TrueCulture(r)),
      developed to characterise drug effects on cells of the human immune system in
      clinical trials, was used to analyse cytokine patterns in the blood samples of 12
      healthy subjects over a period of one month. METHODS: After an overnight fast, 12
      healthy subjects donated blood three times a week on three consecutive days over
      a period of 4 weeks. TruCulture(r) blood collection and whole-blood culture
      systems were used to measure whole-blood leukocyte stimulation. The levels of IL
      2, IL-5, IL-13, IL-6, IL-8, IL-10, IFNgamma, and MCP-1 in the culture
      supernatants were quantified by sandwich ELISA. RESULTS: The pattern of cytokine
      concentrations in the supernatants of the stimulated whole-blood cultures was
      highly individual, but considerably stable over the whole observation period of 4
      weeks. CONCLUSIONS: By using TruCulture(r) it seems feasible to determine subject
      specific cytokine reference patterns, for example under healthy conditions, or
      before starting an experimental treatment, e.g. during a clinical trial, against
      which changes in the behaviour of the immune system can be detected more
      accurately in future.

PMID- 22853195
TI  - Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do
      not correct the increased sensitivity for ischemia-reperfusion injury.
AB  - BACKGROUND: The number of patients with diabetes or the metabolic syndrome
      reaches epidemic proportions. On top of their diabetic cardiomyopathy, these
      patients experience frequent and severe cardiac ischemia-reperfusion (IR)
      insults, which further aggravate their degree of heart failure. Food restriction
      and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in
      these patients but the effects on cardiac IR injury have never been investigated.
      In this study, we tested the hypothesis that 1 degrees  food restriction and 2
      degrees  ACE-I reduce infarct size and preserve cardiac contractility after IR
      injury in mouse models of diabetes and the metabolic syndrome. METHODS: C57Bl6/J
      wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and
      double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin
      and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects
      of 12 weeks food restriction or ACE-I on infarct size and load-independent left
      ventricular contractility after 30 min regional cardiac ischemia were
      investigated. Differences between groups were analyzed for statistical
      significance by Student's t-test or factorial ANOVA followed by a Fisher's LSD
      post hoc test. RESULTS: Infarct size was larger in ob/ob and DKO versus WT.
      Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in
      ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35
      40%, or ACE-I did not reduce the effect of IR. CONCLUSION: ACE-I and food
      restriction do not correct the increased sensitivity for cardiac IR-injury in
      mouse models of type II diabetes and the metabolic syndrome.

PMID- 22853197
TI  - Nicotine patches and quitline counseling to help hospitalized smokers stay quit:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Hospitalized smokers often quit smoking, voluntarily or
      involuntarily; most relapse soon after discharge. Extended follow-up counseling
      can help prevent relapse. However, it is difficult for hospitals to provide
      follow-up and smokers rarely leave the hospital with quitting aids (for example,
      nicotine patches). This study aims to test a practical model in which hospitals
      work with a state cessation quitline. Hospital staff briefly intervene with
      smokers at bedside and refer them to the quitline. Depending on assigned
      condition, smokers may receive nicotine patches at discharge or extended quitline
      telephone counseling post-discharge. This project establishes a practical model
      that lends itself to broader dissemination, while testing the effectiveness of
      the interventions in a rigorous randomized trial. METHODS/DESIGN: This randomized
      clinical trial (N = 1,640) tests the effect of two interventions on long-term
      quit rates of hospitalized smokers in a 2 x 2 factorial design. The interventions
      are (1) nicotine patches (eight-week, step down program) dispensed at discharge
      and (2) proactive telephone counseling provided by the state quitline after
      discharge. Subjects are randomly assigned into: usual care, nicotine patches,
      telephone counseling, or both patches and counseling. It is hypothesized that
      patches and counseling have independent effects and their combined effect is
      greater than either alone. The primary outcome measure is thirty-day abstinence
      at six months; a secondary outcome is biochemically validated smoking status.
      Cost-effectiveness analysis is conducted to compare each intervention condition
      (patch alone, counseling alone, and combined interventions) against the usual
      care condition. Further, this study examines whether smokers' medical diagnosis
      is a moderator of treatment effect. Generalized linear (binomial) mixed models
      will be used to study the effect of treatment on abstinence rates. Clustering is
      accounted for with hospital-specific random effects. DISCUSSION: If this model is
      effective, quitlines across the U.S. could work with interested hospitals to set
      up similar systems. Hospital accreditation standards related to tobacco cessation
      performance measures require follow-up after discharge and provide additional
      incentive for hospitals to work with quitlines. The ubiquity of quitlines,
      combined with the consistency of quitline counseling delivery as centralized
      state operations, make this partnership attractive. TRIAL REGISTRATION: Smoking
      cessation in hospitalized smokers NCT01289275. Date of registration February 1,
      2011; date of first patient August 3, 2011.

PMID- 22853297
TI  - Aspartame in conjunction with carbohydrate reduces insulin levels during
      endurance exercise.
AB  - BACKGROUND: As most sport drinks contain some form of non-nutritive sweetener
      (e.g. aspartame), and with the variation in blood glucose regulation and insulin
      secretion reportedly associated with aspartame, a further understanding of the
      effects on insulin and blood glucose regulation during exercise is warranted.
      Therefore, the aim of this preliminary study was to profile the insulin and blood
      glucose responses in healthy individuals after aspartame and carbohydrate
      ingestion during rest and exercise. FINDINGS: Each participant completed four
      trials under the same conditions (45 min rest + 60 min self-paced intense
      exercise) differing only in their fluid intake: 1) carbohydrate (2% maltodextrin
      and 5% sucrose (C)); 2) 0.04% aspartame with 2% maltodextrin and 5% sucrose
      (CA)); 3) water (W); and 4) aspartame (0.04% aspartame with 2% maltodextrin (A)).
      Insulin levels dropped significantly for CA versus C alone (43%) between pre
      exercise and 30 min, while W and A insulin levels did not differ between these
      time points. CONCLUSIONS: Aspartame with carbohydrate significantly lowered
      insulin levels during exercise versus carbohydrate alone.

PMID- 22853296
TI  - Association between gene expression of metabolizing enzymes and esophageal
      squamous cell carcinomas in China.
AB  - Epidemiological studies have indicated that the incidence of esophageal squamous
      cell carcinoma (ESCC) is associated with environmental exposure to mutagens and
      carcinogens. To determine whether the basal expression level of genes involved in
      metabolism of carcinogens is associated with the risk of ESCC, a case-control
      study of 100 patients with newly diagnosed, untreated ESCC and 117 healthy
      controls was performed, and the relative expression levels of four metabolism
      genes (CYP2E1, GSTP1, MTHFR, and NQO1) were determined with quantitative real
      time reverse transcription-polymerase chain reaction in peripheral blood
      mononuclear cells (PBMCs). Analyzed with the mean of relative expression level in
      the controls as the cut-off point, the result exhibited that the increased risk
      for ESCC was significantly associated with reduced expression of GSTP1 (odds
      ratio [OR]=3.644, 95% confidence interval [CI: 1.947-6.823) and NQO1 (OR=1.870,
      95% CI: 1.046-3.345). When adjusted for age, sex, smoking status, and alcohol
      use, the increased risk for ESCC was significantly associated with reduced
      expression of GSTP1, MTHFR, and NQO1, and GSTP1 mRNA showed a steady association
      with the risk for ESCC (OR=2.640) in the model of stepwise regression analysis.
      Reduced expression of GSTP1 in PBMCs was significantly associated with the risk
      for ESCC, suggesting an important etiology clue to the early progression of ESCC
      in the Huaian population of China.

PMID- 22853298
TI  - Intramolecular 1,8-hydrogen atom transfer reactions in disaccharide systems
      containing furanose units.
AB  - A previously developed 1,8-hydrogen atom transfer (HAT) reaction promoted by 6-O
      yl alkoxyl radicals between the two pyranose units in Hexp-(1->4)-Hexp
      disaccharides has been extended to other systems containing at least a furanose
      ring in their structures. In Penf-(1->3)-Penf (A) and Hexp-(1->3)-Penf (B)
      disaccharides, the 1,8-HAT reaction and concomitant cyclization to a 1,3,5
      trioxocane ring are in competition with radical beta-scission of the C4-C5 bond
      and formation of dehomologated products. The influence of the stereoelectronic
      beta-oxygen effect on the beta-scission and consequently on the 1,8-HAT reaction
      has been studied using the four possible isomeric d-furanoses. d-xylo- and d-lyxo
      derivatives afforded preferentially 1,8-HAT products, whereas d-arabino- and d
      ribo-derivatives gave exclusively direct beta-scission of the alkoxyl radical.
      When the 6-O-yl radical is on a pyranose ring, as occurs in Penf-(1->4)-Hexp (C),
      it has been shown to provide the cyclized products exclusively.

PMID- 22853299
TI  - Converting an intranet site to the cloud: using CampusGuides to refresh a library
      portal.
AB  - After a major redesign project in 2002, Mayo Clinic Libraries' heavily used
      intranet portal remained largely static. Library staff were unable to make
      substantive design changes or introduce tools that would make the content more
      dynamic. CampusGuides offered a practical, user-friendly, web-based solution to
      add dynamic content to the library site. A task force was formed both to
      establish design and style guidelines that would integrate with the library site
      and to plan the conversion of content to CampusGuides. Converting intranet site
      content to CampusGuides gave the task force the opportunity to examine, re
      imagine, and revitalize site content.

PMID- 22853295
TI  - Characterization of microRNAs expression during maize seed development.
AB  - BACKGROUND: MicroRNAs (miRNAs) are approximately 20-22 nt non-coding RNAs that
      play key roles in many biological processes in both animals and plants. Although
      a number of miRNAs were identified in maize, the function of miRNA in seed
      development was merely discussed. RESULTS: In this study, two small RNA libraries
      were sequenced, and a total reads of 9,705,761 and 9,005,563 were generated from
      developing seeds and growing leaves, respectively. Further analysis identified
      125 known miRNAs in seeds and 127 known miRNAs in leaves. 54 novel miRNAs were
      identified and they were not reported in other plants. Additionally, some miRNA*s
      of these novel miRNAs were detected. Potential targets of all novel miRNAs were
      predicted based on our strict criteria. In addition to deep-sequencing, miRNA
      microarray study confirmed the higher expression of several miRNAs in seeds. In
      summary, our results indicated the distinct expression of miRNAs during seed
      development. CONCLUSIONS: We had identified 125 and 127 known miRNAs from seeds
      and leaves in maize, and a total of 54 novel miRNAs were discovered. The
      different miRNA expression profile in developing seeds were revealed by both
      sequencing and microarray studies.

PMID- 22853300
TI  - Combining history of medicine and library instruction: an innovative approach to
      teaching database searching to medical students.
AB  - Library faculty members at the Health Sciences Library at the LSU Health
      Shreveport campus offer a database searching class for third-year medical
      students during their surgery rotation. For a number of years, students completed
      "ten-minute clinical challenges," but the instructors decided to replace the
      clinical challenges with innovative exercises using The Edwin Smith Surgical
      Papyrus to emphasize concepts learned. The Surgical Papyrus is an online resource
      that is part of the National Library of Medicine's "Turning the Pages" digital
      initiative. In addition, vintage surgical instruments and historic books are
      displayed in the classroom to enhance the learning experience.

PMID- 22853301
TI  - Rethinking the reference collection: exploring benchmarks and e-book
      availability.
AB  - Librarians in the Health Sciences Library System at the University of Pittsburgh
      explored the possibility of developing an electronic reference collection that
      would replace the print reference collection, thus providing access to these
      valuable materials to a widely dispersed user population. The librarians
      evaluated the print reference collection and standard collection development
      lists as potential benchmarks for the electronic collection, and they determined
      which books were available in electronic format. They decided that the low
      availability of electronic versions of titles in each benchmark group rendered
      the creation of an electronic reference collection using either benchmark
      impractical.

PMID- 22853302
TI  - Changing the face of reference: adapting biomedical and health information
      services for the classroom, clinic, and beyond.
AB  - This article describes how the reference department at a large academic health
      sciences library evolved to address the clinical and research information needs
      of the parent organization without losing its close connections to the classroom
      and curriculum. Closing the reference desk, moving to on-call and house call
      models, designing positions such as clinical research librarian and basic
      biomedical sciences librarian, finding alternative funding to grow the
      department, providing technology and training to facilitate librarians' work, and
      developing programming for and taking advice from library clients facilitated
      efforts to create a relevant presence and solidify the library's place in the
      university community.

PMID- 22853303
TI  - Health literacy for older adults: using evidence to build a model educational
      program.
AB  - HeLP MN Seniors was a pilot program aimed at developing an evidence-based
      educational program to improve health literacy/health information literacy skills
      in older adults. A two-part workshop series was created and a pilot test was
      conducted with residents of a senior living community. After attending the pilot
      workshops, older adults reported that they used several workshop tools and tips,
      were more empowered to ask questions, and were more successful in finding online
      health information. Based upon evidence gathered through formal program
      evaluation, the pilot curriculum was further customized and developed into a
      model educational program that has been made available for use by others.

PMID- 22853304
TI  - Statistical insight: a review.
AB  - Statistical Insight is a database that offers the ability to search across
      multiple sources of data, including the federal government, private
      organizations, research centers, and international intergovernmental
      organizations in one search. Two sample searches on the same topic, a basic and
      an advanced, were conducted to evaluate the database.

PMID- 22853305
TI  - An introduction to web scale discovery systems.
AB  - This article explores the basic principles of web-scale discovery systems and how
      they are being implemented in libraries. "Web scale discovery" refers to a class
      of products that index a vast number of resources in a wide variety formats and
      allow users to search for content in the physical collection, print and
      electronic journal collections, and other resources from a single search box.
      Search results are displayed in a manner similar to Internet searches, in a
      relevance ranked list with links to online content. The advantages and
      disadvantages of these systems are discussed, and a list of popular discovery
      products is provided. A list of library websites with discovery systems currently
      implemented is also provided.

PMID- 22853306
TI  - The librarian as a member of the education department team: using web 2.0
      technologies to improve access to education materials and information.
AB  - The part-time solo librarian at St. James Healthcare in Butte, Montana, serves
      physicians, staff, patients, and other health care professionals in the area. The
      library is part of the Education Department within the hospital's organizational
      structure. Recent developments have expanded the requirements of the Education
      Department, creating new challenges. The librarian is a member of the team
      developing solutions to the many ways that continuing education needs have to be
      met for the staff and physicians. A free website that houses education
      information and material is one of the projects that has been created and is
      maintained by the librarian.

PMID- 22853307
TI  - Librarian-facilitated problem-based learning course in a school of dental
      medicine.
AB  - While problem-based learning has been used in medical practice for several
      decades, dental education was slower to adapt this education model. However, as
      dental curricula are embracing this pedagogy, dental and other health sciences
      librarians are in a position to provide important curricular support. This
      article will detail one dental liaison librarian's experience with facilitating a
      problem-based, case-based studies course within the curriculum of a dental
      school.

PMID- 22853313
TI  - In vivo evaluation of DSAEK interface with scanning-laser confocal microscopy.
AB  - BACKGROUND: Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) allows
      selective replacement of the endothelium. Post-operative haze and particles can
      affect the interface quality and, ultimately, visual outcome. In this study, we
      evaluated DSAEK interface with in vivo laser confocal microscopy (LCM) in order
      to: (i) correlate interface status with best corrected visual acuity, and (ii)
      with time from surgery; (iii) correlate interface particle number with best
      corrected visual acuity. Host-donor interface was imaged and graded using a
      published reflectivity scale. Particles at the interface were counted. METHODS:
      18 eyes of 16 patients (6 males and 10 females); mean age: 74 +/- 8.3 years which
      underwent DSAEK were examined by means of in vivo laser confocal microscopy
      between 1 and 24 months after surgery. Host-donor interface was imaged and graded
      using a published reflectivity scale. Particles present at the interface were
      counted. RESULTS: Interface reflectivity was 2.17 +/- 1.2 and significantly
      correlated with visual acuity (Spearman correlation coefficient -0.83; P <
      0.001), and with time after surgery (Spearman correlation coefficient -0.87; P <
      0.001). Visual acuity was 0.67 +/- 0.27. The number of particles was 205 +/-
      117.8; no correlation was found between this number and visual acuity (Spearman
      correlation coefficient -0.41; P = 0.15). CONCLUSION: DSAEK interface imaged with
      LCM is helpful in diagnosing poor host-donor interface quality in DSAEK surgery.
      A good quality interface is related to a better visual acuity. Moreover, the
      quality of the interface appears to improve as time passes from the surgery.
      Interface quality is related with visual acuity and improves with time from
      surgery. LCM should be considered as an added tool in post-DSAEK follow-up of
      patients. Finally, our study shows that the presence of particles does not
      influence visual outcome.

PMID- 22853314
TI  - Editorial comment to development and external validation of lymph node density
      cut-off points in prospective series of radical cystectomy and pelvic lymph node
      dissection.

PMID- 22853315
TI  - DECRA investigators' response to "The future of decompressive craniectomy for
      diffuse traumatic brain injury" by Honeybul et al.

PMID- 22853316
TI  - The GATA1s isoform is normally down-regulated during terminal haematopoietic
      differentiation and over-expression leads to failure to repress MYB, CCND2 and
      SKI during erythroid differentiation of K562 cells.
AB  - BACKGROUND: Although GATA1 is one of the most extensively studied haematopoietic
      transcription factors little is currently known about the physiological functions
      of its naturally occurring isoforms GATA1s and GATA1FL in humans-particularly
      whether the isoforms have distinct roles in different lineages and whether they
      have non-redundant roles in haematopoietic differentiation. As well as being of
      general interest to understanding of haematopoiesis, GATA1 isoform biology is
      important for children with Down syndrome associated acute megakaryoblastic
      leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease
      pathogenesis. METHODS: Human primary cells and cell lines were analyzed using
      GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes
      were used to model the effects of the two isoforms on in vitro haematopoietic
      differentiation. RESULTS: We found no evidence for lineage specific use of GATA1
      isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down
      regulated during in vitro induction of terminal megakaryocytic and erythroid
      differentiation in the cell line K562. In addition, transgenic K562-GATA1s and
      K562-GATA1FL cells have distinct gene expression profiles both in steady state
      and during terminal erythroid differentiation, with GATA1s expression
      characterised by lack of repression of MYB, CCND2 and SKI. CONCLUSIONS: These
      findings support the theory that the GATA1s isoform plays a role in the
      maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells
      and must be down-regulated prior to terminal differentiation. In addition our
      data suggest that SKI may be a potential therapeutic target for the treatment of
      children with DS-AMKL.

PMID- 22853317
TI  - Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine
      receptor type 4 and matrix metallopeptidase-9.
AB  - CONTEXT: Nobiletin is one of the citrus bioflavonoids and can be found in citrus
      fruits such as lemons, oranges, tangerines, and grapefruits. The most studied
      properties of nobiletin are its anti-inflammatory and anticancer activities.
      OBJECTIVE: The exact mechanisms of how nobiletin inhibits tumor metastasis and
      invasion are still not fully understood. In this study, we screened various
      natural compounds to down-modulate the CXC chemokine receptor-4 (CXCR4) and
      matrix metallopeptidase-9 (MMP-9). MATERIALS AND METHODS: The effect of nobiletin
      on the constitutive expressions of CXCR4 and MMP-9, MMP-9 enzymatic activity,
      associated nuclear factor kappaB (NF-kappaB) and mitogen-activated protein
      kinases (MAPKs) activation, and tumor cell invasion in human breast cancer cells
      was investigated. CXCR4 and MMP-9 expression were evaluated via reverse
      transcription polymerase chain reaction (RT-PCR) and western blotting. NF-kappaB
      activation was also evaluated by electrophoretic mobility shift assay (EMSA). In
      addition, the antimetastatic effects of nobiletin were determined by gelatin
      zymography and invasion assay. RESULTS: Nobiletin down-regulated both the
      constitutive expressions of CXCR4 and MMP-9 in human breast cancer cells with
      IC(50) values of 32 and 24 uM, respectively. Nobiletin also suppressed MMP-9
      enzymatic activity and tumor cell invasion under noncytotoxic concentrations.
      Neither proteasome inhibition nor lysosomal stabilization had any effect on the
      nobiletin-induced decrease in CXCR4 expression. A detailed study of the
      underlying molecular mechanisms revealed that the regulation of the down
      regulation of CXCR4 and MMP-9 were at the transcriptional level, as indicated by
      the down-regulation of mRNA expression and the suppression of the constitutive NF
      kappaB and MAPKs activation. DISCUSSION AND CONCLUSION: Our results indicate, for
      the first time, that nobiletin is a novel blocker of CXCR4 and MMP-9 expressions
      and thus has the potential to suppress metastasis of breast cancer.

PMID- 22853318
TI  - The evolution of selective estrogen receptor modulators in osteoporosis therapy.
AB  - Selective estrogen receptor modulators (SERMs), which exhibit estrogen receptor
      agonist or antagonist activity based on the target tissue, have evolved through
      multiple generations for the prevention and/or treatment of postmenopausal
      osteoporosis. An ideal SERM would protect bone without stimulating the breast or
      endometrium. Raloxifene, lasofoxifene, and bazedoxifene have demonstrated unique
      preclinical profiles. Raloxifene, lasofoxifene, and bazedoxifene have shown
      significant reduction in the risk of vertebral fracture and improvement in bone
      mineral density versus placebo in postmenopausal women with osteoporosis.
      Raloxifene has been shown to reduce the risk of non-vertebral fractures in women
      with severe prevalent fractures at baseline. Lasofoxifene 0.5 mg, but not
      lasofoxifene 0.25 mg, has shown reduction in the incidence of non-vertebral
      fractures. Bazedoxifene 20 mg has been associated with a significant reduction in
      the risk of non-vertebral fracture versus placebo and raloxifene 60 mg in women
      at higher baseline fracture risk. Neither raloxifene, lasofoxifene, nor
      bazedoxifene has shown an increase in the incidence of endometrial hyperplasia or
      carcinoma. All SERMs have been associated with increased venous thromboembolic
      events and hot flushes. SERMs are effective alternatives for women who cannot
      tolerate or are unwilling to take bisphosphonates and may be appropriate for
      women at higher risk of fracture, particularly younger women who expect to remain
      on therapy for many years and are concerned about the long-term safety of
      bisphosphonates.

PMID- 22853319
TI  - The impact of African ethnicity and migration on pregnancy in women living with
      HIV in the UK: design and methods.
AB  - BACKGROUND: The number of reported pregnancies in women with diagnosed HIV in the
      UK increased from 80 in 1990 to over 1400 in 2010; the majority were among women
      born in sub-Saharan Africa. There is a paucity of research on how social
      adversity impacts upon pregnancy in HIV positive women in the UK; furthermore,
      little is known about important outcomes such as treatment uptake and return for
      follow-up after pregnancy. The aim of this study was to examine pregnancy in
      African women living with HIV in the UK. METHODS AND DESIGN: This was a two phase
      mixed methods study. The first phase involved analysis of data on approximately
      12,000 pregnancies occurring between 2000 and 2010 reported to the UK's National
      Study of HIV in Pregnancy and Childhood (NSHPC). The second phase was based in
      London and comprised: (i) semi-structured interviews with 23 pregnant African
      women living with HIV, 4 health care professionals and 2 voluntary sector
      workers; (ii) approximately 90 hours of ethnographic fieldwork in an HIV charity;
      and (iii) approximately 40 hours of ethnographic fieldwork in a Pentecostal
      church. DISCUSSION: We have developed an innovative methodology utilising
      epidemiological and anthropological methods to explore pregnancy in African women
      living with HIV in the UK. The data collected in this mixed methods study are
      currently being analysed and will facilitate the development of appropriate
      services for this group.

PMID- 22853320
TI  - Rapid removal of Hg(II) from aqueous solutions using thiol-functionalized Zn
      doped biomagnetite particles.
AB  - The surfaces of Zn-doped biomagnetite nanostructured particles were
      functionalized with (3-mercaptopropyl)trimethoxysilane (MPTMS) and used as a high
      capacity and collectable adsorbent for the removal of Hg(II) from water. Fourier
      transform infrared spectroscopy (FTIR) confirmed the attachment of MPTMS on the
      particle surface. The crystallite size of the Zn-doped biomagnetite was ~17 nm,
      and the thickness of the MPTMS coating was ~5 nm. Scanning transmission electron
      microscopy and dynamic light scattering analyses revealed that the particles
      formed aggregates in aqueous solution with an average hydrodynamic size of 826 +/
      32 nm. Elemental analyses indicate that the chemical composition of the
      biomagnetite is Zn(0.46)Fe(2.54)O(4), and the loading of sulfur is 3.6 mmol/g.
      The MPTMS-modified biomagnetite has a calculated saturation magnetization of 37.9
      emu/g and can be separated from water within a minute using a magnet. Sorption of
      Hg(II) to the nanostructured particles was much faster than other commercial
      sorbents, and the Hg(II) sorption isotherm in an industrial wastewater follows
      the Langmuir model with a maximum capacity of ~416 mg/g, indicating two -SH
      groups bonded to one Hg. This new Hg(II) sorbent was stable in a range of
      solutions, from contaminated water to 0.5 M acid solutions, with low leaching of
      Fe, Zn, Si, and S (<10%).

PMID- 22853321
TI  - Bioactivity comparison of extracts from various parts of common and tartary
      buckwheats: evaluation of the antioxidant- and angiotensin-converting enzyme
      inhibitory activities.
AB  - BACKGROUND: Buckwheat flour and buckwheat sprouts possess antioxidant properties,
      and previous studies have reported on buckwheat flour displaying an inhibitory
      activity for angiotensin-I converting enzyme (ACE). Information is lacking on the
      bioactivity of other parts of the buckwheat, such as the seed hulls and plant
      stalks. This study investigates the ACE inhibitory activity and antioxidant
      activity of various parts of 2 types of buckwheat, namely, common buckwheat
      (Fagopyrum esculentum Moench) and tartary buckwheat (Fagopyrum tataricum Gaertn).
      RESULTS: The extract of common hulls extracted using 50% (v/v)-ethanol solvent
      presented a remarkable inhibitory activity. The value of IC50 is 30 MUg ml-1. The
      extracts of both common and tartary hulls extracted using 50% (v/v)-ethanol
      solvent demonstrated an antioxidant activity that is superior to that of other
      extracts. CONCLUSION: This study determined that the ethanolic extract of the
      hulls of common buckwheat presented more favorable antioxidant and ACE inhibitory
      abilities. However, the correlation of antioxidant activity and ACE inhibitory
      activity for all 18 types of extracts is low. The ACE inhibitory activity could
      have been caused by a synergistic effect of flavonoids or from other unidentified
      components in the extracts. The ethanolic extract of common hulls demonstrated
      remarkable ACE inhibitory activity and is worthy of further animal study.

PMID- 22853323
TI  - X-ray absorption study of the solvation structure of Cu2+ in methanol and
      dimethyl sulfoxide.
AB  - The solvation structure of Cu(2+) in methanol (MeOH) and dimethyl sulfoxide
      (DMSO) has been determined by studying both the extended X-ray absorption fine
      structure (EXAFS) and the X-ray absorption near-edge structure (XANES) regions of
      the K-edge absorption spectra. The EXAFS technique has been found to provide a
      very accurate determination of the next-neighbor coordination distances, but it
      is inconclusive in the determination of the coordination numbers and polyhedral
      environment. Conversely, quantitative analysis of the XANES spectra unambiguously
      shows the presence of an average 5-fold coordination in both the MeOH and DMSO
      solution, ruling out the usually proposed octahedral Jahn-Teller distorted
      geometry. The EXAFS and XANES techniques provide coherent values of the Cu-O
      first-shell distances that are coincident in the two solvents. This investigation
      shows that the combined analysis of the EXAFS and XANES data allows a reliable
      determination of the structural properties of electrolyte solutions, which is
      very difficult to achieve with other experimental techniques.

PMID- 22853324
TI  - Linked versus unlinked hospital discharge data on hip fractures for estimating
      incidence and comorbidity profiles.
AB  - BACKGROUND: Studies comparing internally linked (person-identifying) and unlinked
      (episodes of care) hospital discharge data (HDD) on hip fractures have mainly
      focused on incidence overestimation by unlinked HDD, but little is known about
      the impact of overestimation on patient profiles such as comorbidity estimates.
      In view of the continuing use of unlinked HDD in hip fracture research and the
      desire to apply research results to hip fracture prevention, we concurrently
      assessed the accuracy of both incidence and comorbidity estimates derived from
      unlinked HDD compared to those estimated from internally linked HDD. METHODS: We
      analysed unlinked and internally linked HDD between 01 July 2005 and 30 June
      2008, inclusive, from Victoria, Australia to estimate the incidence of hospital
      admission for fall-related hip fracture in community-dwelling older people aged
      65+ years and determine the prevalence of comorbidity in patients. Community
      dwelling status was defined as living in private residence, supported residential
      facilities or special accommodation but not in nursing homes. We defined
      internally linked HDD as the reference standard and calculated measures of
      accuracy of fall-related hip fracture incidence by unlinked HDD using standard
      definitions. The extent to which comorbidity prevalence estimates by unlinked HDD
      differed from those by the reference standard was assessed in absolute terms.
      RESULTS: The sensitivity and specificity of a standard approach for estimating
      fall-related hip fracture incidence using unlinked HDD (i.e. omitting records of
      in-hospital deaths, inter-hospital transfers and readmissions within 30 days of
      discharge) were 94.4% and 97.5%, respectively. The standard approach and its
      variants underestimated the prevalence of some comorbidities and altered their
      ranking. The use of more stringent selection criteria led to major improvements
      in all measures of accuracy as well as overall and specific comorbidity
      estimates. CONCLUSIONS: This study strongly supports the use of linked rather
      than unlinked HDD in injury research. In health systems where linked HDD are
      unavailable, current approaches for identifying incident hip fractures may be
      enhanced by incorporating additional evidence-based criteria.

PMID- 22853325
TI  - Health and economic effects from linking bedside and outpatient tobacco cessation
      services for hospitalized smokers in two large hospitals: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Extended smoking cessation follow-up after hospital discharge
      significantly increases abstinence. Hospital smoke-free policies create a period
      of 'forced abstinence' for smokers, thus providing an opportunity to integrate
      tobacco dependence treatment, and to support post-discharge maintenance of
      hospital-acquired abstinence. This study is funded by the National Heart, Lung,
      and Blood Institute (1U01HL1053231). METHODS/DESIGN: The Inpatient Technology
      Supported Assisted Referral study is a multi-center, randomized clinical
      effectiveness trial being conducted at Kaiser Permanente Northwest (KPNW) and at
      Oregon Health & Science University (OHSU) hospitals in Portland, Oregon. The
      study assesses the effectiveness and cost-effectiveness of linking a practical
      inpatient assisted referral to outpatient cessation services plus interactive
      voice recognition (AR + IVR) follow-up calls, compared to usual care inpatient
      counseling (UC). In November 2011, we began recruiting 900 hospital patients age
      >=18 years who smoked >=1 cigarettes in the past 30 days, willing to remain
      abstinent postdischarge, have a working phone, live within 50 miles of the
      hospital, speak English, and have no health-related barriers to participation.
      Each site will randomize 450 patients to AR + IVR or UC using a 2:1 assignment
      strategy. Participants in the AR + IVR arm will receive a brief inpatient
      cessation consult plus a referral to available outpatient cessation programs and
      medications, and four IVR follow-up calls over seven weeks postdischarge.
      Participants do not have to accept the referral. At KPNW, UC participants will
      receive brief inpatient counseling and encouragement to self-enroll in available
      outpatient services. The primary outcome is self-reported thirty-day smoking
      abstinence at six months postrandomization for AR + IVR participants compared to
      usual care. Additional outcomes include self-reported and biochemically confirmed
      seven-day abstinence at six months, self-reported seven-day, thirty-day, and
      continuous abstinence at twelve months, intervention dose response at six and
      twelve months for AR + IVR recipients, incremental cost-effectiveness of AR + IVR
      intervention compared to usual care at six and twelve months, and health-care
      utilization and expenditures at twelve months for AR + IVR recipients compared to
      UC. DISCUSSION: This study will provide important evidence for the effectiveness
      and cost-effectiveness of linking hospital-based tobacco treatment specialists'
      services with discharge follow-up care. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01236079.

PMID- 22853326
TI  - Quantitative RNA-Seq analysis in non-model species: assessing transcriptome
      assemblies as a scaffold and the utility of evolutionary divergent genomic
      reference species.
AB  - BACKGROUND: How well does RNA-Seq data perform for quantitative whole gene
      expression analysis in the absence of a genome? This is one unanswered question
      facing the rapidly growing number of researchers studying non-model species.
      Using Homo sapiens data and resources, we compared the direct mapping of
      sequencing reads to predicted genes from the genome with mapping to de novo
      transcriptomes assembled from RNA-Seq data. Gene coverage and expression analysis
      was further investigated in the non-model context by using increasingly divergent
      genomic reference species to group assembled contigs by unique genes. RESULTS:
      Eight transcriptome sets, composed of varying amounts of Illumina and 454 data,
      were assembled and assessed. Hybrid 454/Illumina assemblies had the highest
      transcriptome and individual gene coverage. Quantitative whole gene expression
      levels were highly similar between using a de novo hybrid assembly and the
      predicted genes as a scaffold, although mapping to the de novo transcriptome
      assembly provided data on fewer genes. Using non-target species as reference
      scaffolds does result in some loss of sequence and expression data, and bias and
      error increase with evolutionary distance. However, within a 100 million year
      window these effect sizes are relatively small. CONCLUSIONS: Predicted gene sets
      from sequenced genomes of related species can provide a powerful method for
      grouping RNA-Seq reads and annotating contigs. Gene expression results can be
      produced that are similar to results obtained using gene models derived from a
      high quality genome, though biased towards conserved genes. Our results
      demonstrate the power and limitations of conducting RNA-Seq in non-model species.

PMID- 22853327
TI  - Nitrogen-induced catalyst restructuring for epitaxial growth of multiwalled
      carbon nanotubes.
AB  - The ability to simply and economically produce carbon nanotubes (CNTs) with a
      defined chiral angle is crucial for the exploitation of nanotubes for their
      electrical properties. We investigate a diverse range of nitrogen sources for
      their ability to control CNT chiral angle via epitaxial growth from highly
      ordered catalyst particles. Through the use of in situ mass and infrared
      spectrometry, we elucidate the mechanism by which these ordered catalyst
      particles are formed, showing that ammonia is a key intermediate in the process.
      Subsequently, the direct addition of a small amount of ammonia to an otherwise
      standard CNT synthesis is shown to be able to form catalyst particles that grow
      single chiral angle multiwalled carbon nanotubes. Variation in the ammonia
      concentration clarifies the catalyst restructuring necessary for the epitaxial
      growth of carbon nanotubes and subsequent chiral angle control. The simple
      addition of a nitrogen source is an attractive route for chiral angle control;
      however, the model also suggests further ways to optimize CNT chiral angle
      distributions as well as to improve CNT and graphene yield and crystallinity.
      This understanding also explains the action of ammonia in its widely used role in
      activating catalyst prior to CNT growth. Finally, this work highlights the uses
      of novel surface geometries that are achievable through multiphase catalysts.

PMID- 22853328
TI  - Hepatitis B virus surface antigen can activate human monocyte-derived dendritic
      cells by nuclear factor kappa B and p38 mitogen-activated protein kinase mediated
      signaling.
AB  - Hepatitis B virus Ag (HBsAg), a major antigen of hepatitis B virus (HBV), is also
      a vaccine component for prevention of HBV infection. Dendritic cells (DCs) of HBV
      carriers reportedly exhibit functional impairment. In this study, the aim was to
      investigate the effect of HBsAg on activation of human monocyte-derived dendritic
      cells (MD-DCs), and the subsequent signal transduction pathway. Treatment of MD
      DCs with HBsAg resulted in enhanced cell surface expression of cluster of
      differentiation 80, CD83, CD86 and major histocompatibility complex class II, and
      increased interleukin (IL)-12 p40, IL-12p70, and IL-10 production. Furthermore,
      HBsAg treatment of MD-DCs with HBsAg resulted in enhanced T cell-stimulatory
      capacity and increased T cell secretion of interferon and IL-10. The pathway of
      MD-DCs activation by HBsAg was further investigated in the present study.
      Inhibition of nuclear factor (NF)-kappa B (kappaB) by helenalin and p38 mitogen
      activated protein kinase (MAPK) by SB203580 prevented production of IL-12 p40, IL
      12 p70, and IL-10. HBsAg also augmented MAPK phosphorylation. Thus, cytokine
      secretion of human MD-DCs by HBsAg is blocked by inhibition of the NF-kappaB and
      p38 MAPK pathways. Likewise, decreased inhibition of kappa B alpha concentrations
      and MAPK phosphorylation are critical for MD-DC maturation by HBsAg. These
      findings may provide a strategy for improving the prophylactic and therapeutic
      efficacy of vaccines and tumor therapies that utilize these pathways.

PMID- 22853329
TI  - First enantioselective total synthesis of (+)-(R)-Pinnatolide using an asymmetric
      domino allylation reaction.
AB  - An efficient total synthesis of (+)-(R)-Pinnatolide is described. As a key step
      an asymmetric multicomponent domino allylation reaction of methyl levulinate is
      used to form the quaternary stereogenic center in a highly selective way.

PMID- 22853427
TI  - Sequence-dependent synergistic inhibition of human glioma cell lines by combined
      temozolomide and miR-21 inhibitor gene therapy.
AB  - Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse
      drug resistance in cancer treatments. In this study, we explored the most
      effective schedule of the miR-21 inhibitor (miR-21i) and Temozolomide (TMZ)
      combined treatment in human glioma cells. Three tumor cell lines, U251
      phosphatase and tensin homologue (PTEN) mutant, LN229 (PTEN wild-type), and U87
      (PTEN loss of function), were subjected to evaluate the antitumor effects of
      deigned treatments (a predose of miR-21i for 4/8 h and then a subsequent TMZ
      treatment, a predose of TMZ for 4/8 h and then a subsequent miR-21i treatment, or
      a concomitant treatment) in vitro. A synergistic antiproliferative and
      proapoptotic activity was only obtained in U251 and U87 cells when a predose was
      administered for 4 h before the treatment of the other therapeutic agent, while
      the best antitumor effect in LN229 cells was achieved by using the concomitant
      treatment. Our data indicate that the effect of sequence and timing of
      administration is dependent on the PTEN status of cell lines. The best
      suppression effect was achieved by a maximal inhibition of STAT3 and
      phosphorylated STAT3, in PTEN loss of function cells. Our results reveal that
      both the sequence and the timing of administration are crucial in glioma
      combination therapy.

PMID- 22853428
TI  - A simple and fast fabrication of a both self-cleanable and deep-UV antireflective
      quartz nanostructured surface.
AB  - Both self-cleanability and antireflectivity were achieved on quartz surfaces by
      forming heptadecafluoro-1,1,2,2-tetrahydrodecyltrichlorosilane self-assembled
      monolayer after fabrication of nanostructures with a mask-free method. By
      exposing polymethylmethacrylate spin-coated quartz plates to O2 reactive ion
      etching (RIE) and CF4 RIE successively, three well-defined types of nanopillar
      arrays were generated: A2, A8, and A11 patterns with average pillar widths of 33
      +/- 4 nm, 55 +/- 5 nm, and 73 +/- 14 nm, respectively, were formed. All the
      fabrication processes including the final cleaning can be finished within 4 h.
      All nanostructured quartz surfaces exhibited contact angles higher than 155
      degrees  with minimal water droplet adhesiveness and enhanced transparency (due
      to antireflectivity) over a broad spectral range from 350 to 900 nm. Furthermore,
      A2 pattern showed an enhanced antireflective effect that extends to the deep-UV
      range near 190 nm, which is a drawback region in conventional thin-film-coating
      approaches as a result of thermal damage. Because, by changing the conditions of
      successive RIE, the geometrical configurations of nanostructure arrays can be
      easily modified to meet specific needs, the newly developed fabrication method is
      expected to be applied in various optic and opto-electrical areas.PACS codes:
      06.60.Ei; 81.65.Cf; 81.40.Vw.

PMID- 22853429
TI  - Reactive histiocytosis of the orbit and posterior segment in a dog.
AB  - We present a case of reactive histiocytic disease involving the orbit, optic
      nerve, retina, and choroid in a Border Collie dog initially presenting for vision
      loss. Long-term partial return of vision has been achieved with systemic
      immunosuppression. Anterior segment and ocular surface manifestations of reactive
      histiocytic disease in dogs are relatively common. Posterior segment and orbital
      involvement, however, are minimally documented in the existing literature. To the
      authors' knowledge, this is the first report of disease confined to the orbit and
      posterior segment as well as the first report of vision loss as a presenting
      complaint for reactive histiocytic disease. Clinical, magnetic resonance imaging,
      cytologic, and histopathologic findings are reviewed.

PMID- 22853430
TI  - HER3 signalling is regulated through a multitude of redundant mechanisms in HER2
      driven tumour cells.
AB  - HER2 (human epidermal growth factor receptor-2)-amplified tumours are
      characterized by constitutive signalling via the HER2-HER3 co-receptor complex.
      Although phosphorylation activity is driven entirely by the HER2 kinase, signal
      volume generated by the complex is under the control of HER3, and a large
      capacity to increase its signalling output accounts for the resiliency of the
      HER2-HER3 tumour driver and accounts for the limited efficacies of anti-cancer
      drugs designed to target it. In the present paper we describe deeper insights
      into the dynamic nature of HER3 signalling. Signalling output by HER3 is under
      several modes of regulation, including transcriptional, post-transcriptional,
      translational, post-translational and localizational control. These redundant
      mechanisms can each increase HER3 signalling output and are engaged in various
      degrees depending on how the HER3/PI3K (phosphoinositide 3-kinase)/Akt/mTOR
      (mammalian target of rapamycin) signalling network is disturbed. The highly
      dynamic nature of HER3 expression and signalling, and the plurality of downstream
      elements and redundant mechanisms that function to ensure HER3 signalling
      throughput identify HER3 as a major signalling hub in HER2-amplified cancers and
      a highly resourceful guardian of tumorigenic signalling in these tumours.

PMID- 22853431
TI  - Effects of high-sulphur water on hepatic gene expression of steers fed fibre
      based diets.
AB  - Sulphur-induced polioencephalomalacia (sPEM), a neurological disorder affecting
      ruminants, is frequently associated with the consumption of high-sulphur (S)
      water and subsequent poor performance. Currently, there is no economical method
      for S removal from surface water sources, and alternative water sources are
      typically neither readily available nor cost-effective. Determination of genes
      differentially expressed in response to high-S water consumption may provide a
      better understanding of the physiology corresponding to high dietary S and
      ultimately lead to the development of treatment and prevention strategies. The
      objective of this study was to determine changes in gene expression in the liver,
      an organ important for S metabolism, of fibre-fed steers consuming high-S water.
      For this study, liver tissues were collected on the final day of a trial from
      yearling steers randomly assigned to low-S water control (566 mg/kg SO4 ; n =
      24), high-S water (3651 mg/kg SO4 ; n = 24) or high-S water plus clinoptilolite
      supplemented at either 2.5% (n = 24) or 5.0% (n = 24) of diet dry matter (DM).
      Microarray analyses on randomly selected healthy low-S control (n = 4) and high-S
      (n = 4; no clinoptilolite) steers using the Affymetrix GeneChip Bovine Genome
      Array revealed 488 genes upregulated (p < 0.05) and 154 genes downregulated (p <
      0.05) in response to the high- vs. low-S water consumption. Real-time RT-PCR
      confirmed the upregulation (p < 0.10) of seven genes involved in inflammatory
      response and immune functions. Changes in such genes suggest that ruminant
      animals administered high-S water may be undergoing an inflammation or immune
      response, even if signs of sPEM or compromised health are not readily observed.
      Further study of these, and other affected genes, may deliver new insights into
      the physiology underlying the response to high dietary S, ultimately leading to
      the development of treatments for high S-affected ruminant livestock. 

PMID- 22853432
TI  - Functional gene polymorphism of matrix metalloproteinase-1 is associated with
      benign hyperplasia of myo- and endometrium in the Russian population.
AB  - AIMS: Estrogen-dependent hyperplasia of myo- and endometrium manifests as uterine
      leiomyoma or adenomyosis. We studied possible associations between common
      polymorphisms of matrix metalloproteinase (MMP) genes and clinical features of
      uterine hyperplasia. PATIENTS AND METHODS: One hundred seventy female patients
      with uterine leiomyoma (46.6+/-0.5 years) were observed. Clinical diagnosis was
      based on physical examination, ultrasonography, and histological data. MMP-1 (
      1607 1G/2G, rs1799750) and MMP-3 (-1171 5A/6A, rs3025058) were genotyped with
      allele-specific polymerase chain reaction (PCR) of leukocyte DNA. Clinical and
      genetic data were evaluated using nonparametric statistics. RESULTS:
      Distributions of MMP-1 and MMP-3 promoter alleles among patients and population
      controls were similar and corresponded to the Hardy-Weinberg equilibrium (HWE).
      Detectable tumor growth and adenomyosis were observed, respectively, in 71% and
      55% of cases. Steady-state leiomyoma correlated with a higher prevalence of the
      MMP-1 1G/1G genotype (p=0.02 by chi(2) test). Accelerated tumor growth correlated
      with higher frequency of the MMP-1 2G allele [odds ratio (OR)=2.048, p=0.039,
      chi(2)=4.2611, confidence interval (CI)=(1.032-4.062)]. MMP-1 2G was also
      associated with multinodular growth [OR=3.561, p=0.01249, chi(2)=6.24, CI=(1.261
      10.058)]. The MMP-1 2G allele tended to increase in patients with adenomyosis
      [OR=1.525, p=0.054, chi(2)=3.71, CI=(0.992-2.345)]. CONCLUSION: Our pilot study
      suggests that the 2G (-1607)MMP-1 genotype may be a potential risk marker of myo-
      and endometrial hyperplasia.

PMID- 22853433
TI  - The effects of low-dose nepsilon-(carboxymethyl)lysine (CML) and nepsilon
      (carboxyethyl)lysine (CEL), two main glycation free adducts considered as
      potential uremic toxins, on endothelial progenitor cell function.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk of
      cardiovascular disease (CVD). Endothelial progenitor cell (EPCs) dysfunction
      plays a key role in this pathogenesis. Uremic retention toxins have been reported
      to be in associated with EPC dysfunction. Advanced glycation end-products (AGEs)
      free adducts, including nepsilon-(carboxymethyl)lysine (CML) and nepsilon
      (carboxyethyl)lysine (CEL), are formed by physiological proteolysis of AGEs and
      released into plasma for urinary excretion. They are retained in CKD patients and
      are considered to be potential uremic toxins. Though AGEs have been demonstrated
      to impair EPC function in various ways, the effect of AGE free adducts on EPC
      function has not been studied. Thus, we examined the role of CML and CEL in the
      regulation of growth-factor-dependent function in cultured human EPCs and the
      mechanisms by which they may affect EPC function. METHODS: Late outgrowth EPCs
      were incubated with different concentrations of CML or CEL for up to 72 hours.
      Cell proliferation was determined using WST-1 and BrdU assays. Cell apoptosis was
      tested with annexin V staining. Migration and tube formation assays were used to
      evaluate EPC function. RESULTS: Though CML and CEL were determined to have anti
      proliferative effects on EPCs, cells treated with concentrations of CML and CEL
      in the range found in CKD patients had no observable impairment on migration or
      tube formation. CML and CEL did not induce EPC apoptosis. The reduced growth
      response was accompanied by significantly less phosphorylation of mitogen
      activated protein kinases (MAPKs). CONCLUSIONS: Our study revealed that CML and
      CEL at uremic concentrations have low biological toxicity when separately tested.
      The biologic effects of AGE free adducts on the cardiovascular system merit
      further study.

PMID- 22853434
TI  - Regioselective formation of acrolein-derived cyclic 1,N(2)-propanodeoxyguanosine
      adducts mediated by amino acids, proteins, and cell lysates.
AB  - Acrolein (Acr) is a major component in cigarette smoke and a ubiquitous
      environmental pollutant. It is also formed as a product of lipid peroxidation.
      Following ring closure via the Michael addition, Acr modifies deoxyguanosine (dG)
      in DNA by forming cyclic 1,N(2)-propanodeoxyguanosine adducts (OHPdG). The
      reactions of Acr with dG yield, depending on the direction of ring closure, two
      regioisomers, alpha- and gamma-OHPdG, in approximately equal amounts. However,
      previous (32)P-postlabeling studies showed that the gamma isomers were detected
      predominantly in the DNA of rodent and human tissues. Because of the potential
      differential biological activity of the isomeric OHPdG adducts, it is important
      to confirm and study the chemical basis of the regioselective formation of gamma
      isomers in vivo. In this study, it is confirmed that gamma-OHPdG adducts are
      indeed the major isomers formed in vivo as evidenced by a LC-MS/MS method
      specifically developed for Acr-derived dG adducts. Furthermore, we have shown
      that the formation of gamma-isomers is increased in the presence of amino
      containing compounds, including amino acids, proteins, and cell lysates. A
      product of Acr and arginine that appears to mediate the regioselective formation
      of gamma isomers was identified, but its structure was not fully characterized
      due to its instability. This study demonstrates that intracellular amino
      containing compounds may influence the regiochemistry of the formation of OHPdG
      adducts and reveals a mechanism for the preferential formation of gamma-OHPdG by
      Acr in vivo.

PMID- 22853435
TI  - A preliminary study of the safety of red light phototherapy of tissues harboring
      cancer.
AB  - OBJECTIVE: Red light phototherapy is known to stimulate cell proliferation in
      wound healing. This study investigated whether low-level light therapy (LLLT)
      would promote tumor growth when pre-existing malignancy is present. BACKGROUND
      DATA: LLLT has been increasingly used for numerous conditions, but its use in
      cancer patients, including the treatment of lymphedema or various unrelated
      comorbidities, has been withheld by practitioners because of the fear that LLLT
      might result in initiation or promotion of metastatic lesions or new primary
      tumors. There has been little scientific study of oncologic outcomes after use of
      LLLT in cancer patients. METHODS: A standard SKH mouse nonmelanoma UV-induced
      skin cancer model was used after visible squamous cell carcinomas were present,
      to study the effects of LLLT on tumor growth. The red light group (n=8) received
      automated full body 670 nm LLLT delivered twice a day at 5 J/cm(2) using an LED
      source. The control group (n=8) was handled similarly, but did not receive LLLT.
      Measurements on 330 tumors were conducted for 37 consecutive days, while the
      animals received daily LLLT. RESULTS: Daily tumor measurements demonstrated no
      measurable effect of LLLT on tumor growth. CONCLUSIONS: This experiment suggests
      that LLLT at these parameters may be safe even when malignant lesions are
      present. Further studies on the effects of photoirradiation on neoplasms are
      warranted.

PMID- 22853437
TI  - Syntheses of carbocyclic analogues of alpha-D-glucosamine, alpha-D-mannose, alpha
      D-mannuronic acid, beta-L-idosamine, and beta-L-gulose.
AB  - A versatile synthesis of orthogonally protected derivatives of carba-alpha-D
      glucosamine, carba-alpha-D-mannose, carba-alpha-D-mannuronic acid, carba-beta-L
      idosamine, and carba-beta-L-gulose from methyl alpha-D-mannoside is described.
      Our synthetic strategy utilizes the palladium-promoted Ferrier carbocyclization
      and persistent butane-2,3-diacetal protection to produce a key chiral
      cyclohexanone intermediate, from which all five carbasugar derivatives can
      readily be obtained.

PMID- 22853436
TI  - Frequency doubling technology, optical coherence technology and pattern
      electroretinogram in ocular hypertension.
AB  - BACKGROUND: To assess which of three methods, namely, optical coherence
      tomography (OCT), pattern electroretinogram (PERG) or frequency-doubling
      technology (FDT), is the most sensitive and specific for detecting early
      glaucomatous damage in ocular hypertension (OH). METHODS: Fifty-two patients with
      OH (24 men and 28 women, mean age of 56 +/- 9.6 years) with an intraocular
      pressure (IOP) > 21 mm Hg and fifty-two control patients (25 men and 27 women,
      mean age of 54.8 +/- 10.4 years) with IOP < 21 mm Hg, were assessed. All the
      patients had normal visual acuity, normal optic disk and normal perimetric
      indices.All subjects underwent OCT, FDT and PERG. Data were analyzed with
      unpaired t-tests, Chi-square test and Receiver Operating Characteristic (ROC)
      curve analyses. RESULTS: In patients with OH, OCT showed retinal nerve fiber
      layer (RNFL) thinner than in control group in the superior quadrant (130.16 +/-
      10.02 vs 135.18 +/- 9.27 MUm, respectively; p < 0.011) and inferior quadrant
      (120.14 +/- 11.0 vs 132.68 +/- 8.03 MUm; p < 0.001). FDT showed a significantly
      higher pattern standard deviation (PSD) (3.46  +/- 1.48 vs 1.89 +/- 0.7 dB; p <
      0.001). With respect to PERG, only the amplitude showed significant differences
      (p < 0.044) between the two groups. ROC curve analysis revealed a sensitivity and
      specificity of 92% and 86%, respectively, for FDT-PSD (with an area under the ROC
      curve of 0.940), whereas with OCT, a sensitivity of 82% and a specificity of 74%
      was recorded in the inferior RNFL quadrant (with an area under the ROC curve of
      0.806) finally with PERG amplitude we found a sensitivity of 52% and specificity
      of 77% (with an area under the ROC curve of 0.595). CONCLUSIONS: FDT is the most
      sensitive and specific method for detecting early glaucomatous damage in eyes
      with OH, and together with OCT, can be useful in identifying those patients who
      may develop glaucoma. TRIAL REGISTRATION: ISRCT number: ISRCTN70295497.

PMID- 22853438
TI  - The release of IL-31 and IL-13 after nasal allergen challenge and their relation
      to nasal symptoms.
AB  - BACKGROUND: IL-31, a recently discovered member of the gp130/IL-6 cytokine
      family, is mainly expressed by human mast cells and T helper type 2 cells. IL-31
      is a key trigger of atopic dermatitis. Recent studies also suggest a role of IL
      31 in the pathogenesis of other allergic diseases including allergic rhinitis. In
      the present study we studied the release of IL-31 and IL-13 in allergen
      challenged allergic rhinitis patients. METHODS: Seven seasonal allergic
      volunteers underwent unilateral nasal provocation with allergen (and a control
      challenge) with the disc method out of the allergy season. Nasal symptom scores
      (rhinorrhea, itching, sneezing, obstruction) and bilateral nasal secretions were
      quantified before and after allergen provocation. IL-13 and IL-31 in nasal
      secretions and serum were measured by electrochemiluminescent immunoassay or
      ELISA, respectively. RESULTS: Nasal allergen challenge induced the typical
      clinical symptoms and physiological changes. IL-31 and IL-13 in nasal secretions
      increased in four and five, respectively, volunteers at 5 h after allergen but
      not after control challenge. We observed correlation trends between nasal IL-31
      concentrations and IL-13 concentrations (r = 0.9, p = 0.002), and IL-31 contents
      and symptom scores (r = 0.9, p = 0.013) 5 h after allergen provocation. No IL-31
      could be detected contralaterally or systemically in the sera. CONCLUSIONS: The
      observed local upregulation of IL-31 mainly during the late phase reaction after
      nasal allergen challenge suggests a role of IL-31 in allergic rhinitis. In which
      way IL-31 modulates the inflammatory reaction and type 2 responses in allergic
      rhinitis remains to be investigated.

PMID- 22853439
TI  - Neuroprotective effects of sulforaphane after contusive spinal cord injury.
AB  - Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium
      mobilization, glutamate toxicity, the release of proinflammatory factors, and
      depletion of reduced glutathione (GSH) at the site of injury. Induction of the
      Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH
      depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction,
      and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli,
      is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to
      upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone
      oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate
      inflammation by inhibiting the nuclear factor-kappaB (NF-kappaB) pathway, and the
      enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor
      (MIF). Our study examined systemic administration of SF in a rat model of
      contusion SCI, in an effort to utilize its indirect antioxidant and anti
      inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50
      mg/kg) were administered at 10 min and 72 h after contusion SCI. SF (50 mg/kg)
      treatment resulted in both acute and long-term beneficial effects, including
      upregulation of the phase 2 antioxidant response at the injury site, decreased
      mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord,
      inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor
      function, and an increased number of serotonergic axons caudal to the lesion
      site. These findings demonstrate that SF provides neuroprotective effects in the
      spinal cord after injury, and could be a candidate for therapy of SCI.

PMID- 22853440
TI  - Phytochemicals and biological studies of plants from the genus Balanophora.
AB  - This review focus on the phytochemical progress and biological studies of plants
      from the genus Balanophora (Balanophoraceae) over the past few decades, in which
      most plants growth in tropical and subtropical regions of Asia and Oceania, and
      nearly 20 species ranged in southwest China. These dioeciously parasitic plants
      are normally growing on the roots of the evergreen broadleaf trees, especially in
      the family of Leguminosae, Ericaceae, Urticaceae, and Fagaceae. The plants are
      mainly used for clearing away heat and toxic, neutralizing the effect of
      alcoholic drinks, and as a tonic for the treatment of hemorrhoids, stomachache
      and hemoptysis. And it has been used widely throughtout local area by Chinese
      people.Cinnamic acid derivative tannins, possessing a phenylacrylic acid
      derivative (e. g. caffeoyl, coumaroyl, feruloyl or cinnamoyl), which connected to
      the C(1) position of a glucosyl unit by O-glycosidic bond, are the characteristic
      components in genus Balanophora. In addition, several galloyl, caffeoyl and
      hexahydroxydiphenoyl esters of dihydrochalcone glucosides are found in B.
      tobiracola, B. harlandii, and B. papuana. Other compounds like phenylpropanoids,
      flavonoids, terpenoids and sterols are also existed. And their biological
      activities, such as radical scavenging activities, HIV inhibiting effects, and
      hypoglycemic effects are highlighted in the review.

PMID- 22853442
TI  - Evaluation of the costs and resource use associated with adjuvant chemotherapy
      for breast cancer in France.
AB  - OBJECTIVES: There is a paucity of recent data on breast cancer costs,
      particularly on the burden of chemotherapy. The present study was designed to
      estimate resource use and costs associated with the current standard of care for
      adjuvant chemotherapy for breast cancer. METHODS: Costs and resource use were
      assessed by retrospective analysis of medical records at a single comprehensive
      cancer care center, Hopital Tenon, Paris, France. Data were extracted from files
      of female patients having undergone surgical resection of breast cancer between
      January-July 2010. Patients were included if they received chemotherapy at the
      hospital and had medical records available. Patients were followed from the start
      of adjuvant chemotherapy (including pre-chemotherapy) to the end of treatment.
      Costs were collected for each resource use item from a societal perspective using
      standard, published sources and expressed in 2011 Euros (?). Limitations of the
      analysis included the single-center study design and the use of pre-defined
      questionnaires on resource use (which may conservatively estimate costs).
      RESULTS: A total of 62 patients were included in the study with a mean age of ~54
      years. Most patients had stage II (50.8%) or stage III (40.7%) disease.
      Anthracycline plus taxane-based chemotherapy regimens were most commonly
      prescribed (77% of patients). Mean cost of adjuvant chemotherapy was estimated to
      be ~?15,740 per patient from a societal perspective. The acquisition costs of
      chemotherapy agents were responsible for 26% of the total, with lost productivity
      (27%), chemotherapy administration (19%), and adverse events (16%) also
      contributing substantially. CONCLUSIONS: Evaluation of costs in patients with non
      metastatic breast cancer in France has shown that the costs of adjuvant
      chemotherapy are substantial. The main components of total cost were the cost of
      chemotherapy agents, lost productivity, chemotherapy administration, and
      management and prevention of adverse events.

PMID- 22853441
TI  - Attenuation of quorum sensing in the pathogen Acinetobacter baumannii using non
      native N-Acyl homoserine lactones.
AB  - Many bacterial pathogens use quorum sensing (QS) to control virulence. As a
      result, the development of methods to intercept QS has attracted significant
      interest as a potential anti-infective therapy. Acinetobacter baumannii has
      emerged as a pan-drug-resistant pathogen and displays a remarkable ability to
      persist in hospital settings despite desiccation and antimicrobial treatment.
      Recent studies have shown that A. baumannii QS mutants have limited motility and
      fail to form mature biofilms; these phenotypes are linked to its ability to
      persist on biotic and abiotic surfaces and increase its pathogenicity. A.
      baumannii uses N-(3-hydroxydodecanoyl)-l-homoserine lactone (OH-dDHL) and its
      putative cognate receptor, AbaR, for QS. We sought to identify non-native ligands
      capable of blocking or promoting AbaR activity in A. baumannii for use as
      chemical probes to modulate QS phenotypes in this pathogen. We screened a focused
      library of synthetic, non-native N-acyl homoserine lactones (AHLs) to identify
      such compounds, and several highly potent antagonists and agonists were
      uncovered, with IC(50) and EC(50) values in the low micromolar range,
      respectively. The strongest AbaR antagonists largely contained aromatic acyl
      groups, whereas the AbaR agonists closely resembled OH-dDHL. Notably, the 10 most
      potent AbaR antagonists also strongly inhibited A. baumannii motility, and five
      antagonists reduced biofilm formation in A. baumannii by up to 40%. The discovery
      of these compounds is significant, as they represent, to our knowledge, the first
      non-native modulators of QS in A. baumannii to be reported and could find utility
      as new tools to study the role and timing of QS phenotypes in A. baumannii
      infections.

PMID- 22853443
TI  - Willingness to pay for diabetes drug therapy in type 2 diabetes patients: based
      on LEAD clinical programme results.
AB  - OBJECTIVE: The purpose of this study was to investigate the preferences of people
      with diabetes for liraglutide vs other glucose lowering drugs, based on outcomes
      of clinical trials. METHODS: Willingness to pay (WTP) for diabetes drug treatment
      was assessed by combining results from a recent WTP study with analysis of
      results from the Liraglutide Effect and Action in Diabetes (LEAD) programme. The
      LEAD programme included six randomised clinical trials with 3967 participants
      analysing efficacy and safety of liraglutide 1.2 mg (LEAD 1-6 trials),
      rosiglitazone (LEAD 1 trial), glimepiride (LEAD 2-3 trials), insulin glargine
      (LEAD 5 trial), and exenatide (LEAD 6 trial). The WTP survey used discrete choice
      experimental (DCE) methodology to evaluate the convenience and clinical effects
      of glucose lowering treatments. RESULTS: People with type 2 diabetes were
      prepared to pay an extra ?2.64/day for liraglutide compared with rosiglitazone,
      an extra ?1.94/day compared with glimepiride, an extra ?3.36/day compared with
      insulin glargine, and an extra ?0.81/day compared with exenatide. Weight loss was
      the largest component of WTP for liraglutide compared with rosiglitazone,
      glimepiride, and insulin glargine. Differences in the administration of the two
      drugs was the largest component of WTP for liraglutide (once daily anytime)
      compared with exenatide (twice daily with meals). A limitation of the study was
      that it was based on six clinical trials where liraglutide was the test drug, but
      each trial had a different comparator, therefore the clinical effects of
      liraglutide were much better documented than the comparators. CONCLUSIONS: WTP
      analyses of the clinical results from the LEAD programme suggested that
      participants with type 2 diabetes were willing to pay appreciably more for
      liraglutide than other glucose lowering treatments. This was driven by the
      relative advantage of weight loss compared with rosiglitazone, glimepiride, and
      insulin glargine, and administration frequency compared with exenatide.

PMID- 22853444
TI  - Bazedoxifene/conjugated estrogens for menopausal symptom treatment and
      osteoporosis prevention.
AB  - Postmenopausal women with vasomotor and vaginal symptoms are commonly treated
      with estrogens or combined estrogen/progestin therapy (hormone therapy). However,
      hormone therapy is associated with some safety and tolerability concerns and its
      benefit/risk profile may vary for women based on their time since menopause. The
      tissue selective estrogen complex (TSEC) pairs a selective estrogen receptor
      modulator with one or more estrogens, with the goal of relieving menopausal
      symptoms and preserving bone mineral density without stimulating the breast or
      endometrium. Bazedoxifene/conjugated estrogens (BZA/CE) is the first TSEC in
      clinical development. BZA 20 mg/CE 0.45 and 0.625 mg have been shown in phase-3
      clinical trials to significantly improve hot flushes and vulvar/vaginal atrophy
      measures in symptomatic postmenopausal women and to prevent bone loss in
      postmenopausal women at risk for osteoporosis while ensuring endometrial safety.
      These doses of BZA/CE have also demonstrated significant improvements in quality
      of-life scores, sleep parameters, and treatment satisfaction compared with
      placebo. BZA 20 mg/CE 0.45 and 0.625 mg showed high cumulative rates of
      amenorrhea and low rates of breast pain, similar to those with placebo. The
      favorable treatment effects seen with BZA/CE were generally consistent in women <
      5 or >= 5 years since menopause. Based on its demonstrated efficacy and safety in
      women both closer to or further from menopause, BZA/CE may be an appropriate
      alternative to hormone therapy for the treatment of menopausal symptoms and the
      prevention of osteoporosis.

PMID- 22853445
TI  - Translationally controlled tumour protein (TCTP) is present in human cornea and
      increases in herpetic keratitis.
AB  - BACKGROUND: Translationally controlled tumour protein is a multifunctional
      calcium binding protein which has an important role in apoptosis, calcium levels
      balance and immunological response. The aim of this study was to evaluated the
      presence and distribution of TCTP in healthy human corneas and to identify and
      characterize the presence and distribution of this protein in human normal
      cornea. Since recent studies suggest that apoptosis, calcium levels and
      immunological mechanisms play a role in the pathogenesis of herpetic stromal
      keratitis, we studied TCTP expression in this disease. METHODS: We evaluated the
      expression of TCTP at both RNA messanger and protein level by using reverse
      transcriptase analysis, immunoblotting and immunohistochemistry in 10 healthy
      samples cornea: four obtained after penetrating keratoplasty and six from eyes
      enucleated for other pathologies. Finally, we analysed by immunohistochemistry
      ten paraffin-embedded samples of Herpes simplex virus keratitis collected at
      Siena Department of Human Pathology and Oncology: 5 had clinically quiescent
      disease and 5 had active corneal inflammation. RESULTS: Reverse transcriptase and
      immunoblotting demonstrated TCTP expression in cornea as a 22,000 Da molecular
      weight band corresponding to the molecular weight of this protein.
      Immunohistochemically, all the layers of normal corneal epithelium showed TCTP
      cytoplasmic expression. TCTP was, also, observed in keratocytes and in the
      endothelium. In Herpes simplex virus keratitis samples, strong expression of TCTP
      was evident in stromal cells, in the inflammatory infiltrate and in neo-vessels.
      CONCLUSIONS: In this preliminary study we demonstrated, for the first time, the
      presence of TCTP in human cornea, suggesting a potential role in the pathogenesis
      of herpes virus keratitis. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3306813447428149.

PMID- 22853447
TI  - Intestinal drug transport via the proton-coupled amino acid transporter PAT1
      (SLC36A1) is inhibited by Gly-X(aa) dipeptides.
AB  - The oral absorption of some drug substances is mediated by nutrient transporters.
      As a consequence, nutrients and drugs may compete for available transporters, and
      interactions at the level of intestinal absorption are possible. Recently, we
      have identified delta-aminolevulinic acid, Gly-Gly, and Gly-Sar as substrates of
      the amino acid transporter PAT1. The aim of the present study is to investigate
      if other Gly-containing dipeptides interact with PAT1, and whether they can
      inhibit PAT1 mediated drug absorption, in vitro and in vivo. The in vitro methods
      included two-electrode voltage clamp measurements on hPAT1 expressing  Xenopus
      laevis  oocytes, which were used to investigate the PAT1-mediated transport of 17
      different Gly-containing dipeptides (Gly-X(aa) or X(aa)-Gly). Also, the
      transepithelial transport of the PAT1 substrate gaboxadol was investigated across
      Caco-2 cell monolayers in the presence of different dipeptides. The in vivo part
      consisted of a pharmacokinetic study in rats following oral administration of
      gaboxadol and preadministration of 200 mg/kg dipeptide. The results showed that
      in hPAT1 expressing oocytes Gly-Tyr, Gly-Pro, and Gly-Phe inhibited currents
      induced by drug substances. In Caco-2 cell monolayers, Gly-Gly, Gly-Sar, and Gly
      Pro significantly inhibited the PAT1 mediated absorptive transepithelial
      transport of gaboxadol; however, when orally administered to rats, Gly-Gly, Gly
      Sar, Gly-Pro, or Gly-Tyr did not alter the pharmacokinetic profile of gaboxadol.
      In conclusion, the present study identifies selected dipeptides as inhibitors of
      PAT1 mediated drug absorption in various in vitro models.

PMID- 22853446
TI  - Profiling the resting venom gland of the scorpion Tityus stigmurus through a
      transcriptomic survey.
AB  - BACKGROUND: The scorpion Tityus stigmurus is widely distributed in Northeastern
      Brazil and known to cause severe human envenoming, inducing pain, hyposthesia,
      edema, erythema, paresthesia, headaches and vomiting. The present study uses a
      transcriptomic approach to characterize the gene expression profile from the non
      stimulated venom gland of Tityus stigmurus scorpion. RESULTS: A cDNA library was
      constructed and 540 clones were sequenced and grouped into 153 clusters, with one
      or more ESTs (expressed sequence tags). Forty-one percent of ESTs belong to
      recognized toxin-coding sequences, with transcripts encoding antimicrobial toxins
      (AMP-like) being the most abundant, followed by alfa KTx- like, beta KTx-like,
      beta NaTx-like and alfa NaTx-like. Our analysis indicated that 34% of the
      transcripts encode "other possible venom molecules", which correspond to anionic
      peptides, hypothetical secreted peptides, metalloproteinases, cystein-rich
      peptides and lectins. Fifteen percent of ESTs are similar to cellular
      transcripts. Sequences without good matches corresponded to 11%. CONCLUSIONS:
      This investigation provides the first global view of gene expression of the venom
      gland from Tityus stigmurus under resting conditions. This approach enables
      characterization of a large number of venom gland component molecules, which
      belong either to known or non yet described types of venom peptides and proteins
      from the Buthidae family.

PMID- 22853448
TI  - The broad spectrum of unbearable suffering in end-of-life cancer studied in dutch
      primary care.
AB  - BACKGROUND: Unbearable suffering most frequently is reported in end-of-life
      cancer patients in primary care. However, research seldom addresses unbearable
      suffering. The aim of this study was to comprehensively investigate the various
      aspects of unbearable suffering in end-of-life cancer patients cared for in
      primary care. METHODS: Forty four general practitioners recruited end-of-life
      cancer patients with an estimated life expectancy of half a year or shorter. The
      inclusion period was three years, follow-up lasted one additional year. Practices
      were monitored bimonthly to identify new cases. Unbearable aspects in five
      domains and overall unbearable suffering were quantitatively assessed (5-point
      scale) through patient interviews every two months with a comprehensive
      instrument. Scores of 4 (serious) or 5 (hardly can be worse) were defined
      unbearable. The last interviews before death were analyzed. Sources providing
      strength to bear suffering were identified through additional open-ended
      questions. RESULTS: Seventy six out of 148 patients (51%) requested to
      participate consented; the attrition rate was 8%, while 8% were alive at the end
      of follow-up. Sixty four patients were followed up until death; in 60 patients
      interviews were complete. Overall unbearable suffering occurred in 28%. A mean of
      18 unbearable aspects was present in patients with serious (score 4) overall
      unbearable suffering. Overall, half of the unbearable aspects involved the domain
      of traditional medical symptoms. The most frequent unbearable aspects were
      weakness, general discomfort, tiredness, pain, loss of appetite and not sleeping
      well (25%-57%). The other half of the unbearable aspects involved the domains of
      function, personhood, environment, and nature and prognosis of disease. The most
      frequent unbearable aspects were impaired activities, feeling dependent, help
      needed with housekeeping, not being able to do important things, trouble
      accepting the situation, being bedridden and loss of control (27%-55%). The
      combination of love and support was the most frequent source (67%) providing
      strength to bear suffering. CONCLUSIONS: Overall unbearable suffering occurred in
      one in every four end-of-life cancer patients. Half of the unbearable aspects
      involved medical symptoms, the other half concerned psychological, social and
      existential dimensions. Physicians need to comprehensively assess suffering and
      provide psychosocial interventions alongside physical symptom management.

PMID- 22853449
TI  - A macrocyclic beta-iodoallenolate intermediate is key: synthesis of the ABD core
      of phomactin A.
AB  - An enantioselective strategy for the synthesis of phomactin natural products is
      described. The Lewis acid triggered cyclization of a beta-iodoallenolate embedded
      in a 12-membered macrocycle was used to obtain a highly functionalized
      bicyclo[9.3.1]pentadecane in good yield and high diastereoselectivity. This
      iodoenone contains the substituents of the AD ring system of the phomactin family
      of natural products, appropriate for further functionalization. Synthesis of the
      oxadecalin core of phomactin A from the AD iodoenone intermediate was achieved.
      In this unusual strategy, rings A and B are both fashioned within a macrocyclic
      precursor.

PMID- 22853450
TI  - A topical aqueous calcineurin inhibitor for the treatment of naturally occurring
      keratoconjunctivitis sicca in dogs.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of an aqueous
      calcineurin inhibitor, SCY-641, in the treatment of naturally occurring canine
      immune-mediated keratoconjunctivitis sicca (KCS). METHODS: A randomized, double
      masked, placebo-controlled clinical study of 56-day duration was performed in
      dogs with naturally occurring immune-mediated KCS assigned to treatment with
      either topical twice-daily aqueous calcineurin inhibitor solution (SCY-641) or
      artificial tears (placebo) by the study administrator. Clinical examination and
      Schirmer tear tests (STT) were performed prior to therapy and at days 7, 14, 28,
      and 56 after initiation of treatment. RESULTS: Twenty dogs were enrolled in the
      study with ten receiving placebo and 10 receiving SCY-641 in one or both eyes. No
      adverse effects were noted with any treatment. There were no significant
      differences in mean STT values in dogs in group either at day 0 (prior to
      therapy) or after 7 days of treatment. At 14, 28, and 56 days after initiation of
      treatment, mean STT and increase in STT over baseline in dogs treated with SCY
      641 were significantly higher than in dogs treated with placebo (P < 0.04).
      CONCLUSIONS: SCY-641 was well tolerated by dogs with naturally occurring KCS, and
      by 14 days after initiating therapy, dogs treated with SCY-641 had significantly
      higher STT than placebo-treated dogs. These preliminary results indicate that
      topical SCY-641, in a stable clear aqueous solution, is efficacious in a
      spontaneous model of KCS and warrants further evaluation as a treatment of immune
      mediated KCS.

PMID- 22853451
TI  - Plasma neurofilament pNF-H concentration is not increased in acute equine grass
      sickness.
AB  - Although a presumptive diagnosis of acute grass sickness (AGS) can be made on the
      basis of clinical signs, a definitive ante mortem diagnosis currently requires
      histological examination of enteric ganglia. Development of an accurate
      noninvasive ante mortem diagnostic test is therefore warranted. The objective of
      this study was to determine whether quantification of the plasma concentrations
      of the heavily phosphorylated form of major neurofilament subunit NF-H (pNF-H),
      which mirror the degree of axonal degeneration in some human and animal
      neurodegenerative disorders, could distinguish AGS-affected and control horses.
      The pNF-H was quantified in plasma from 20 AGS cases and 20 control horses using
      a commercial enzyme-linked immunosorbent assay kit. Five AGS and 4 control
      samples had detectable pNF-H concentrations (>0.0759 ng/ml). There was no
      significant intergroup difference in pNF-H concentrations. It was concluded that
      plasma pNF-H is not a useful biomarker for the diagnosis of AGS.

PMID- 22853452
TI  - Mn(III)(tetra-biphenyl-porphyrin)-TCNE single-chain magnet via suppression of the
      interchain interactions.
AB  - A single-chain magnet (SCM) of [Mn(TBPP)(TCNE)].4m-PhCl(2) (1), where TBPP(2-) =
      meso-tetra(4-biphenyl)porphyrinate; TCNE(*-) = tetracyanoethenide radical anion;
      m-PhCl(2) = meta-dichlorobenzene, was prepared via suppression of interchain
      interactions. 1 has a one-dimensional alternating Mn(III)(porphrin)-TCNE(*-)chain
      structure similar to those of a family of complexes reported by Miller and co
      workers. From a comparison of the static magnetic properties of 1 with other
      Mn(III)(porphyrin)-TCNE(*-) chains, a magneto-structural correlation between the
      intrachain magnetic exchange and both the dihedral angle between the mean plane
      on [Mn(TBPP)(TCNE)] and Mn-N=C was observed. The ac magnetic susceptibility data
      of 1 could be fit with the Arrhenius law, indicating that slow magnetic
      relaxation and ruling out three-dimensional long-range ordering and spin-glass
      like behavior. The Cole-Cole plot for 1 was semicircular, verifying that it is an
      SCM. Therefore, 1 is an ideal single-chain magnet with significantly strong
      intrachain magnetic exchange interactions beyond the Ising limit.

PMID- 22853454
TI  - The effects of early-age thermal manipulation and daily short-term fasting on
      performance and body temperatures in broiler exposed to heat stress.
AB  - This study was conducted to investigate the effects of thermal manipulation at 5
      days of age and short-term fasting during the warmest part of the day on
      responses to prolonged heat stress of broilers. A total of 240-day-old Ross 308
      female broiler chicks were divided into three groups: control, thermal
      manipulation (chicks were exposed to 36  degrees C for 24 h at 5 days of age) and
      short-term fasting during the warmest part of the day (10.00-17.00 h). Prolonged
      heat stress was induced daily from 28 to 42 days by heating until the ambient
      temperature reached 32-35  degrees C between 10.00 and 17.00 h. Both thermal
      manipulation and short-term fasting resulted in a decrease in rectal temperatures
      and haematocrit values at 35 and 41 days of age. Thermal manipulation improved
      body weight, feed consumption and feed conversion. However, short-term fasting
      caused a reduction in body weight and a deterioration in feed conversion. Short
      term fasting lowered the percentages of carcass, whereas thermal manipulation
      highered breast yield. Both thermal manipulation and short-term fasting decreased
      heart mass and abdominal fat. 

PMID- 22853453
TI  - Nasogastric tube insertion in anesthetized and intubated patients: a new and
      reliable method.
AB  - BACKGROUND: The "Rusch" intubation stylet is used to make endotracheal tube
      intubation easy. We designed this study to evaluate the usage of this equipment
      in the guidance of nasogastric tube (NGT) insertion. METHODS: A total of 103
      patients, aged 23 to 70 years, undergoing gastrointestinal or hepatic surgeries
      that required intraoperative NGT insertions were enrolled into our study. The
      patients were randomly allocated to the control group (Group C) or the stylet
      group (Group S) according to a computerized, random allocation software program.
      In the control group, the NGT was inserted with the patient's head in an
      intubating position. In the stylet group, the NGT was inserted with the
      assistance of a "Rusch" intubation stylet tied together at the tips by a
      slipknot. The success rates of the two methods, the durations of the insertions,
      and the occurrences of complications were recorded. All of the failed cases in
      the control group were subjected to the new technique used in the stylet group,
      and the successful rescue rate was also evaluated. RESULTS: Successful insertions
      were recorded for 52/53 patients (98.1%) in Group S and for 32/50 patients (64%)
      in Group C. The mean insertion times were 39.5 +/- 19.5 seconds in Group C and
      40.3 +/- 23.2 seconds in Group S. Successful rescues of failure cases in Group C
      were achieved in 17/18 patients (94.4%) with the assistance of a "Rusch"
      intubation stylet. CONCLUSIONS: The "Rusch" intubation stylet-guided method is
      reliable with a high success rate of NGT insertion in anesthetized and intubated
      patients. TRIAL REGISTRATION: Institutional Review Board of Chang Gung Memorial
      Hospital (IRB: 98-2669B) and Australian New Zealand Clinical Trials Registry
      (ACTRN12611000423910).

PMID- 22853455
TI  - Characterization of ML-IAP protein stability and physiological role in vivo.
AB  - ML-IAP [melanoma IAP (inhibitor of apoptosis)] is an anti-apoptotic protein that
      is expressed highly in melanomas where it contributes to resistance to apoptotic
      stimuli. The anti-apoptotic activity and elevated expression of IAP family
      proteins in many human cancers makes IAP proteins attractive targets for
      inhibition by cancer therapeutics. Small-molecule IAP antagonists that bind with
      high affinities to select BIR (baculovirus IAP repeat) domains have been shown to
      stimulate auto-ubiquitination and rapid proteasomal degradation of c-IAP1
      (cellular IAP1) and c-IAP2 (cellular IAP2). In the present paper, we report ML
      IAP proteasomal degradation in response to bivalent, but not monovalent, IAP
      antagonists. This degradation required ML-IAP ubiquitin ligase activity and was
      independent of c-IAP1 or c-IAP2. Although ML-IAP is best characterized in
      melanoma cells, we show that ML-IAP expression in normal mammalian tissues is
      restricted largely to the eye, being most abundant in ciliary body epithelium and
      retinal pigment epithelium. Surprisingly, given this pattern of expression, gene
      targeted mice lacking ML-IAP exhibited normal intraocular pressure as well as
      normal retinal structure and function. The results of the present study indicate
      that ML-IAP is dispensable for both normal mouse development and ocular
      homoeostasis.

PMID- 22853456
TI  - Electronic structure of atomically precise graphene nanoribbons.
AB  - Some of the most intriguing properties of graphene are predicted for specifically
      designed nanostructures such as nanoribbons. Functionalities far beyond those
      known from extended graphene systems include electronic band gap variations
      related to quantum confinement and edge effects, as well as localized spin
      polarized edge states for specific edge geometries. The inability to produce
      graphene nanostructures with the needed precision, however, has so far hampered
      the verification of the predicted electronic properties. Here, we report on the
      electronic band gap and dispersion of the occupied electronic bands of atomically
      precise graphene nanoribbons fabricated via on-surface synthesis. Angle-resolved
      photoelectron spectroscopy and scanning tunneling spectroscopy data from armchair
      graphene nanoribbons of width N = 7 supported on Au(111) reveal a band gap of 2.3
      eV, an effective mass of 0.21 m(0) at the top of the valence band, and an energy
      dependent charge carrier velocity reaching 8.2 * 10(5) m/s in the linear part of
      the valence band. These results are in quantitative agreement with theoretical
      predictions that include image charge corrections accounting for screening by the
      metal substrate and confirm the importance of electron-electron interactions in
      graphene nanoribbons.

PMID- 22853458
TI  - High-performance III-V MOSFET with nano-stacked high-k gate dielectric and 3D fin
      shaped structure.
AB  - A three-dimensional (3D) fin-shaped field-effect transistor structure based on
      III-V metal-oxide-semiconductor field-effect transistor (MOSFET) fabrication has
      been demonstrated using a submicron GaAs fin as the high-mobility channel. The
      fin-shaped channel has a thickness-to-width ratio (TFin/WFin) equal to 1. The
      nano-stacked high-k Al2O3 dielectric was adopted as a gate insulator in forming a
      metal-oxide-semiconductor structure to suppress gate leakage. The 3D III-V MOSFET
      exhibits outstanding gate controllability and shows a high Ion/Ioff ratio > 105
      and a low subthreshold swing of 80 mV/decade. Compared to a conventional Schottky
      gate metal-semiconductor field-effect transistor or planar III-V MOSFETs, the III
      V MOSFET in this work exhibits a significant performance improvement and is
      promising for future development of high-performance n-channel devices based on
      III-V materials.

PMID- 22853457
TI  - Mitochondrial DNA mutation screening in an ethnically diverse nonsyndromic
      deafness cohort.
AB  - Deafness is a heterogeneous trait with many known genetic and environmental
      causes. Hereditary hearing loss is an extremely common disorder in the general
      population. Mutations in mitochondrial DNA (mtDNA) are known to be associated
      with nonsyndromic deafness (NSD) and syndromic deafness. The objective of this
      article is to investigate the frequency of common mitochondrial mutations
      (A1555G, G7444A, and A3243G) in an ethnically diverse cohort of probands with NSD
      from South Florida. These patients were ascertained at the University of Miami.
      Polymerase chain reaction-restriction fragment length polymorphism analysis and
      direct sequencing methods were used for mutation screening in a cohort of 217
      patients with NSD. The frequency of common mitochondrial mutations is 1.84%
      (4/217) in this cohort. A1555G and G7444A accounted for four patients with NSD.
      Our mutation frequencies are comparable with those previously reported in other
      populations, indicating that mutations in mtDNA are an important cause of NSD in
      our patient cohort.

PMID- 22853459
TI  - The social and emotional skills of bullies, victims, and bully-victims of
      Egyptian primary school children.
AB  - This study examined whether bullies, victims, bully-victims (who are both bullies
      and victims), and students who reported no or low levels of bullying and
      victimization differed in their levels of social and emotional skills. Data were
      collected from 623 children in fifth and sixth grades from four Egyptian
      elementary schools; their ages ranged from 10 to 12 years. K-means cluster
      analysis revealed four groups: bullies (n = 138), victims (n = 178), bully
      victims (n = 59), and children who were not involved in bullying behaviour (n =
      248). Data were analyzed using multinomial logistic regression. The findings
      indicated that boys were more involved in bullying behaviour than girls, and both
      bullies and bully-victims were less likely to adhere to social rules and
      politeness than children who were not involved in bullying. Both bullies and
      victims were less aware of the physiological reactions of their emotions than
      uninvolved children, and were less able to apply social rules in social
      interaction. Both victims and bully-victims reported less likeability than
      children not involved in bullying. Verbal sharing, attending to others' emotions,
      and analysis of emotions did not have a statistically significant relationship
      with the probabilities of classifying children to any bullying group versus
      children not involved in bullying. Social skills were more important than
      emotional awareness in predicting the likelihood of classifying children in one
      of the three bullying groups versus children who not involved in bullying. The
      main conclusion is that social and emotional skills together may provide an
      effective means of intervention for bullying problems. 

PMID- 22853460
TI  - De novo intracranial collision tumour in previously evacuated intracerebral
      haematoma site.
AB  - The authors report the rare and first documented case of intracranial collision
      tumour occurrence in a previously evacuated intracerebral haematoma site. Surgery
      trauma could predispose to collision tumour occurrence. Research efforts should
      try to reveal the possible pathogenesis of this condition.

PMID- 22853547
TI  - Production, active staining and gas chromatography assay analysis of recombinant
      aminopeptidase P from Lactococcus lactis ssp. lactis DSM 20481.
AB  - The aminopeptidase P (PepP, EC 3.4.11.9) gene from Lactococcus lactis ssp.
      lactis DSM 20481 was cloned, sequenced and expressed recombinantly in E. coli
      BL21 (DE3) for the first time. PepP is involved in the hydrolysis of proline-rich
      proteins and, thus, is important for the debittering of protein hydrolysates. For
      accurate determination of PepP activity, a novel gas chromatographic assay was
      established. The release of L-leucine during the hydrolysis of L-leucine-L
      proline-L-proline (LPP) was examined for determination of PepP activity.
      Sufficient recombinant PepP production was achieved via bioreactor cultivation at
      16  degrees C, resulting in PepP activity of 90 MUkatLPP Lculture-1. After
      automated chromatographic purification by His-tag affinity chromatography
      followed by desalting, PepP activity of 73.8 MUkatLPP Lculture-1 was achieved.
      This was approximately 700-fold higher compared to the purified native PepP
      produced by Lactococcus lactis ssp. lactis NCDO 763 as described in literature.
      The molecular weight of PepP was estimated to be ~ 40 kDa via native-PAGE
      together with a newly developed activity staining method and by SDS-PAGE.
      Furthermore, the kinetic parameters Km and Vmax were determined for PepP using
      three different tripeptide substrates. The purified enzyme showed a pH optimum
      between 7.0 and 7.5, was most active between 50 degrees C and 60 degrees C and
      exhibited reasonable stability at 0 degrees C, 20 degrees C and 37 degrees C over
      15 days. PepP activity could be increased 6-fold using 8.92 mM MnCl2 and was
      inhibited by 1,10-phenanthroline and EDTA.

PMID- 22853548
TI  - Effect of CoherinTM on intraocular pressure, pupil size and heart rate in the
      glaucomatous Beagle: a pilot study.
AB  - OBJECTIVE: To evaluate effects of CoherinTM on intraocular pressure (IOP), pupil
      size (PS), and heart rate (HR) in glaucomatous Beagles in single-dose studies in
      a pilot study. MATERIALS AND METHODS: Intraocular pressure, PS, and HR were
      measured in eight glaucomatous Beagles. One randomly chosen eye received single
      50 MUL doses of differing concentrations of CoherinTM (treated eye) or vehicle
      (placebo-treated eye), and the fellow eye served as the untreated control. After
      the first measurements, a single dose of either CoherinTM or sterile water
      vehicle was instilled in the drug and placebo eyes, respectively. RESULTS: The
      mean +/- SEM diurnal changes in IOP after 0.005%, 0.01%, 0.2%, 0.284%, 1%, 2%,
      and 4% topical CoherinTM once daily were 7.6 +/- 3.2 mmHg, 15.5 +/- 5.3 mmHg,
      11.2 +/- 4.4 mmHg, 11.8 +/- 4.4 mmHg, 19.1 +/- 3.8 mmHg, 5.0 +/- 1.8 mmHg, and
      8.8 +/- 2.8 mmHg, respectively. The declines in IOP were significantly different
      (P < 0.05) from the untreated control eyes with the 0.2% and 0.284% CoherinTM
      treated eyes and suggestive for 1% CoherinTM concentrations. No signs of
      irritation, significant PS, and HR changes were detected in the CoherinTM-treated
      eyes. CONCLUSION: Of seven different concentrations, 2% and 0.248% CoherinTM
      produced significant declines in IOP in the glaucomatous beagle in single-dose
      studies when compared to both untreated control and placebo-treated eyes. One
      percent CoherinTM solution produced significant IOP decreases compared with the
      placebo-treated eye but not the untreated control eyes. No local ocular
      irritation, PS and HR changes were observed in CoherinTM-treated eyes. This pilot
      study suggests that topical CoherinTM has potential as an ocular hypotensive
      agent.

PMID- 22853549
TI  - Classification of pasture habitats by Hungarian herders in a steppe landscape
      (Hungary).
AB  - BACKGROUND: Landscape ethnoecology focuses on the ecological features of the
      landscape, how the landscape is perceived, and used by people who live in it.
      Though studying folk classifications of species has a long history, the
      comparative study of habitat classifications is just beginning. I studied the
      habitat classification of herders in a Hungarian steppe, and compared it to
      classifications of botanists and laymen. METHODS: For a quantitative analysis the
      picture sort method was used. Twenty-three pictures of 7-11 habitat types were
      sorted by 25 herders.'Density' of pictures along the habitat gradient of the
      Hortobagy salt steppe was set as equal as possible, but pictures differed in
      their dominant species, wetness, season, etc. Before sorts, herders were asked to
      describe pictures to assure proper recognition of habitats. RESULTS: Herders
      classified the images into three main groups: (1) fertile habitats at the higher
      parts of the habitat gradient (partos, lit. on the shore); (2) saline habitats
      (szik, lit. salt or saline place), and (3) meadows and marshes (lapos, lit.
      flooded) at the lower end of the habitat gradient. Sharpness of delimitation
      changed along the gradient. Saline habitats were the most isolated from the rest.
      Botanists identified 6 groups. Laymen grouped habitats in a less coherent way.As
      opposed to my expectations, botanical classification was not more structured than
      that done by herders. I expected and found high correspondence between the
      classifications by herders, botanists and laymen. All tended to recognize similar
      main groups: wetlands, "good grass" and dry/saline habitats. Two main factors
      could have been responsible for similar classifications: salient features
      correlated (e.g. salinity recognizable by herders and botanists but not by laymen
      correlated with the density of grasslands or height of vegetation recognizable
      also for laymen), or the same salient features were used as a basis for sorting
      (wetness, and abiotic stress). CONCLUSIONS: Despite all the difficulties of
      studying habitat classifications (more implicit, more variable knowledge than
      knowledge on species), conducting landscape ethnoecological research will
      inevitably reveal a deeper human understanding of biological organization at a
      supraspecific level, where natural discontinuities are less sharp than at the
      species or population level.

PMID- 22853550
TI  - Young people with depression and their experience accessing an enhanced primary
      care service for youth with emerging mental health problems: a qualitative study.
AB  - BACKGROUND: Despite the emergence of mental health problems during adolescence
      and early adulthood, many young people encounter difficulties accessing
      appropriate services. In response to this gap, the Australian Government recently
      established new enhanced primary care services (headspace) that target young
      people with emerging mental health problems. In this study, we examine the
      experience of young people with depression accessing one of these services, with
      a focus on understanding how they access the service and the difficulties they
      encounter in the process. METHOD: Individual, in-depth, audio-recorded interviews
      were used to collect data. Twenty-six young people with depression were recruited
      from a headspace site in Melbourne, Australia. Interpretative phenomenological
      analysis was used to analyse the data. RESULTS: Four overlapping themes were
      identified in the data. First, school counsellors as access mediators, highlights
      the prominent role school counsellors have in facilitating student access to the
      service. Second, location as an access facilitator and inhibitor. Although the
      service is accessible by public transport, it is less so to those who do not live
      near public transport. Third, encountering barriers accessing the service
      initially. Two main service access barriers were experienced: unfamiliarity with
      the service, and delays in obtaining initial appointments for ongoing therapy.
      Finally, the service's funding model acts as an access facilitator and barrier.
      While the model provides a low or no cost services initially, it limits the
      number of funded sessions, and this can be problematic. CONCLUSIONS: Young people
      have contrasting experiences accessing the service. School counsellors have an
      influential role in facilitating access, and its close proximity to public
      transport enhances access. The service needs to become more prominent in young
      people's consciousness, while the appointment system would benefit from providing
      more timely appointments with therapists. The service's funding model is
      important in enabling access initially to young people from low socioeconomic
      backgrounds, but the government needs to reassess the model for those who require
      additional support.

PMID- 22853551
TI  - Effects of a constant-rate infusion of dexmedetomidine on the minimal alveolar
      concentration of sevoflurane in ponies.
AB  - REASONS FOR PERFORMING STUDY: Dexmedetomidine has been administered in the equine
      as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving
      optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant
      anaesthetic sparing effects have been demonstrated in other species, but not in
      horses. OBJECTIVES: To determine the effects of a CRI of dexmedetomidine on the
      minimal alveolar concentration (MAC) of sevoflurane in ponies. METHODS: Six
      healthy adult ponies were involved in this prospective, randomised, crossover,
      blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout
      period). After induction with sevoflurane in oxygen (via nasotracheal tube), the
      ponies were positioned on a surgical table (T0), and anaesthesia was maintained
      with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies
      were randomly allocated to treatment D (dexmedetomidine 3.5 ug/kg bwt i.v. [T10
      T15] followed by a CRI of dexmedetomidine at 1.75 ug/kg bwt/h) or treatment S
      (bolus and CRI of saline at the same volume and rate as treatment D). After T60,
      MAC determination, using a classic bracketing technique, was initiated. Stimuli
      consisted of constant-current electrical stimuli at the skin of the lateral
      pastern region. Triplicate MAC estimations were obtained and averaged in each
      pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas
      monitoring, arterial blood pressure measurement and arterial blood gases.
      Normocapnia was maintained by mechanical ventilation. Analysis of variance
      (treatment and period as fixed factors) was used to detect differences between
      treatments (alpha= 0.05). RESULTS: An intravenous (i.v.) dexmedetomidine CRI
      decreased mean +/- s.d. sevoflurane MAC from 2.42 +/- 0.55 to 1.07 +/- 0.21%
      (mean MAC reduction 53 +/- 15%). CONCLUSIONS AND POTENTIAL RELEVANCE: A
      dexmedetomidine CRI at the reported dose significantly reduces the MAC of
      sevoflurane.

PMID- 22853552
TI  - Ruthenium-catalyzed oxidative C(sp2)-H bond hydroxylation: site-selective C-O
      bond formation on benzamides.
AB  - Well-defined ruthenium carboxylate complexes enabled unprecedented ruthenium
      catalyzed C(sp(2))-H hydroxylations on benzamides with PhI(OAc)(2) as the oxidant
      at a remarkably low catalyst loading of 1.0 mol %.

PMID- 22853553
TI  - Flatfoot in Muller-Weiss syndrome: a case series.
AB  - INTRODUCTION: Spontaneous osteonecrosis of the navicular bone in adults is a rare
      entity, known as Muller-Weiss syndrome. We report here on our experience with six
      patients with Muller-Weiss syndrome accompanied by flatfoot deformity, but on a
      literature search found no reports on this phenomenon. Because the natural
      history and treatment are controversial, an understanding of how to manage this
      deformity may be helpful for surgeons when choosing the most appropriate
      operative procedure. CASE PRESENTATION: Six patients (five women, one man;
      average age, 54 years) with flatfoot caused by osteonecrosis of the navicular
      bone were followed up between January 2005 and December 2008 (mean follow-up
      period, 23.2 months). Conservative treatment, such as physical therapy, and non
      steroidal anti-inflammatory drugs were used, but failed. Physical examinations
      revealed flattening of the medial arch of the involved foot and mild tenderness
      at the mid-tarsal joint. Weight-bearing X-rays (anterior-posterior and lateral
      views), computed tomography, and MRI scans were performed for each case.
      Talonavicular joint arthrodesis was performed in cases of single talonavicular
      joint arthritis. Triple arthrodesis was performed in cases of triple joint
      arthritis to reconstruct the medial arch. Clinical outcomes were assessed using
      the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale; the scores
      were 63.0 pre-operatively and 89.8 post-operatively. All patients developed bony
      fusion. CONCLUSIONS: The reason for the development of flatfoot in patients with
      Muller-Weiss syndrome is unknown. Surgical treatment may achieve favorable
      outcomes in terms of deformity correction, pain relief, and functional
      restoration. The choice of operative procedure may differ in patients with both
      flatfoot and posterior tibial tendon dysfunction.

PMID- 22853554
TI  - Effect of ulinastatin on the expression of iNOS, MMP-2, and MMP-3 in degenerated
      nucleus pulposus cells of rabbits.
AB  - We examined the effects of ulinastatin on the expression of inducible nitric
      oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and matrix
      metalloproteinase-3 (MMP-3) in degenerated nucleus pulposus (NP) cells of rabbits
      induced by interleukin (IL)-1beta in vitro. An in vitro NP cell culture model was
      set up with enzyme digestion. NP cells from adult white rabbits were divided into
      six groups: the normal control group, the ulinastatin control group (320 U/mL
      ulinastatin), the induced group (10 ng/mL IL-1beta), and three inhibition groups
      (IL-1beta followed by 160, 320, or 640 U/mL ulinastatin). After a 2-day culture,
      the NP cells were collected for immunohistochemical staining for MMP-2 and MMP-3
      and spectrophotometric analysis of the amount of iNOS. Immunohistochemical
      staining showed that the expression of MMP-2 and MMP-3 proteins in NP cells
      decreased in the inhibition groups compared with the induced group, which was in
      inverse proportion to the ulinastatin concentration. Spectrophotometric results
      showed that, compared with the induced group, the iNOS content in each inhibition
      group decreased, most significantly in the 320 U/mL group. Ulinastatin
      effectively inhibited the increased expression of MMP-2, MMP-3, and iNOS in
      degenerated NP cells induced by IL-1beta in vitro. It suggests that ulinastatin
      may potentially be useful for clinical therapy of intervertebral disc
      degeneration.

PMID- 22853555
TI  - Physiological and hormonal aspects in female domestic pigeons (Columba livia)
      associated with breeding stage and experience.
AB  - The present study examined the changes in serum biochemical values, hormone
      profiles and ovary prolactin receptor (PRLR) gene expression occurring in female
      domestic pigeons (Columba livia) under different breeding status and experience.
      The egg-laying pigeons had lower calcium, total protein, albumin, prolactin
      levels and higher oestrogen levels than those of incubating birds (p < 0.05).
      First-time breeders had higher (p < 0.05) progesterone levels and lower (p <
      0.05) prolactin levels than that of experienced ones. The levels of oestrogen and
      follicle-stimulating hormone (FSH) increased with age (p < 0.05). The very old
      birds showed a pronounced increase (p < 0.05) in PRL, FSH and progesterone and a
      little decrease in oestrogen. Serum prolactin level was not correlated with the
      ovary PRLR mRNA expression pattern among all the pigeons. Results showed that
      serum physiological profile of female pigeons was correlated with breeding
      status, whereas reproductive hormone levels were correlated with advancing
      breeding experience. It was concluded that female pigeons had a good ability of
      recovering from nutrient loss after each breeding attempts, and the degradation
      of reproductive performance might be attributed to changes in the endocrine
      system. 

PMID- 22853557
TI  - Improved field emission stability from single-walled carbon nanotubes chemically
      attached to silicon.
AB  - Here, we demonstrate the simple fabrication of a single-walled carbon nanotube
      (SWCNT) field emission electrode which shows excellent field emission
      characteristics and remarkable field emission stability without requiring
      posttreatment. Chemically functionalized SWCNTs were chemically attached to a
      silicon substrate. The chemical attachment led to vertical alignment of SWCNTs on
      the surface. Field emission sweeps and Fowler-Nordheim plots showed that the Si
      SWCNT electrodes field emit with a low turn-on electric field of 1.5 V MUm-1 and
      high electric field enhancement factor of 3,965. The Si-SWCNT electrodes were
      shown to maintain a current density of >740 MUA cm-2 for 15 h with negligible
      change in applied voltage. The results indicate that adhesion strength between
      the SWCNTs and substrate is a much greater factor in field emission stability
      than previously reported.

PMID- 22853556
TI  - Peer victimization and prospective changes in children's inferential styles.
AB  - There is evidence that the cognitive vulnerabilities featured in the hopelessness
      theory of depression-inferential styles for the causes, consequences, and self
      worth implications of negative events-increase risk for depression. Given this,
      it is important to understand how these inferential styles develop. In this
      study, we examined the impact of overt and relational peer victimization in a
      multiwave prospective study of 100 children (8-12 years of age) with peer
      victimization and inferential styles assessed every 2 months for 6 months (4
      assessments total). Overt victimization uniquely predicted prospective changes in
      children's inferential styles for consequences and relational victimization
      uniquely predicted changes in inferential styles for self-characteristics. It is
      important to note that these relations were maintained even after controlling for
      the impact of concurrent depressive symptoms. These results add to a growing body
      of research suggesting that peer victimization may increase risk for the
      development of cognitive vulnerability to depression in children.

PMID- 22853558
TI  - Are quantum dots toxic? Exploring the discrepancy between cell culture and animal
      studies.
AB  - Despite significant interest in developing quantum dots (QDs) for biomedical
      applications, many researchers are convinced that QDs will never be used for
      treating patients because of their potential toxicity. The perception that QDs
      are toxic is rooted in two assumptions. Cadmium-containing QDs can kill cells in
      culture. Many researchers then assume that because QDs are toxic to cells, they
      must be toxic to humans. In addition, many researchers classify QDs as a
      homogeneous group of materials. Therefore, if CdSe QDs are harmful, they
      extrapolate this result to all QDs. Though unsubstantiated, these assumptions
      continue to drive QD research. When dosing is physiologically appropriate, QD
      toxicity has not been demonstrated in animal models. In addition, QDs are not
      uniform: each design is a unique combination of physicochemical properties that
      influence biological activity and toxicity. In this Account, we summarize key
      findings from in vitro and in vivo studies, explore the causes of the discrepancy
      in QD toxicological data, and provide our view of the future direction of the
      field. In vitro and in vivo QD studies have advanced our knowledge of cellular
      transport kinetics, mechanisms of QD toxicity, and biodistribution following
      animal injection. Cell culture experiments have shown that QDs undergo design
      dependent intracellular localization and they can cause cytotoxicity by releasing
      free cadmium into solution and by generating free radical species. In animal
      experiments, QDs preferentially enter the liver and spleen following
      intravascular injection, undergo minimal excretion if larger than 6 nm, and
      appear to be safe to the animal. In vitro and in vivo studies show an apparent
      discrepancy with regard to toxicity. Dosing provides one explanation for these
      findings. Under culture conditions, a cell experiences a constant QD dose, but
      the in vivo QD concentration can vary, and the organ-specific dose may not be
      high enough to induce detectable toxicity. Because QDs are retained within
      animals, long-term toxicity may be a problem but has not been established. Future
      QD toxicity studies should be standardized and systematized because
      methodological variability in the current body of literature makes it difficult
      to compare and contrast results. We advocate the following steps for consistent,
      comparable toxicology data: (a) standardize dose metrics, (b) characterize QD
      uptake concentration, (c) identify in vitro models that reflect the cells QDs
      interact with in vivo, and (d) use multiple assays to determine sublethal
      toxicity and biocompatibility. Finally, we should ask more specific toxicological
      questions. For example: "At what dose are 5 nm CdSe QDs that are stabilized with
      mercaptoacetic acid and conjugated to the antibody herceptin toxic to HeLa
      cells?" rather than "Are QDs toxic?" QDs are still a long way from realizing
      their potential as a medical technology. Modifying the current QD toxicological
      research paradigm, investigating toxicity in a case-by-case manner, and improving
      study quality are important steps in identifying a QD formulation that is safe
      for human use.

PMID- 22853559
TI  - Prevalence and risk factors of hypertension based on repeated measurements in
      Chinese children and adolescents.
AB  - OBJECTIVES: This study aimed to determine the prevalence of hypertension from
      repeated blood pressure (BP) measurements, and examine the association between
      hypertension and obesity, as well as other related risk factors, in a Chinese
      pediatric population. METHODS: A total of 6692 children, aged 3-18 years, were
      recruited in 2010. Anthropometric measurements and BP were measured using a
      mercury sphygmomanometer. Those with an elevated BP were screened a second or
      third time at 2-week intervals. "Hypertension" was defined as elevated BP on all
      three occasions. A self-administered questionnaire was completed. RESULTS: The
      prevalence of an elevated BP was 18.2%, 5.1% and 3.1% on the first, second and
      third visits, respectively. The odds ratios (ORs) and 95% confidence intervals
      (CIs) for an elevated BP among obese children were 7.07 (5.94-8.42), 17.23 (12.63
      23.52) and 20.63 (13.69-31.09), and among those with a paternal history of
      hypertension were 1.26 (0.98-1.61), 1.35 (0.90-2.02) and 1.80 (1.15-2.81) on each
      consecutive visit. CONCLUSIONS: Repeated measurements are required to confirm the
      diagnosis of hypertension in children and that obesity and paternal hypertension
      are strongly associated with pediatric hypertension.

PMID- 22853560
TI  - SmI2-mediated intermolecular coupling of gamma-lactam N-alpha-radicals with
      activated alkenes: asymmetric synthesis of 11-hydroxylated analogues of the lead
      compounds CP-734432 and PF-04475270.
AB  - We report, for the first time, the synthesis of 8-aza-analogues of PGE2. The SmI2
      mediated cross coupling reactions of gamma-lactam-hemiaminal 9, lactam 2-pyridyl
      sulfide 17, and lactam 2-pyridyl sulfone 18 with activated alkenes/alkyne were
      first developed, giving the corresponding gamma-lactams in 49-78%, 45-75%, and 75
      90%, respectively. The reactions of lactam 2-pyridyl sulfide and 2-pyridyl
      sulfone proceeded with >=12:1 trans-diastereoselectivities. This represents the
      first intermolecular coupling reaction of the gamma-lactam N-alpha-alkyl radicals
      of types B, B1, and B2 with activated alkenes. Two radical-based mechanisms were
      suggested. The asymmetric synthesis of the 11-hydroxylated analogue of the highly
      selective EP4 receptor agonist PF-04475270 (30), the 11-hydroxylated analogue of
      ocular hypotensive CP-734432 (31), compounds 35 and 36 have been achieved on the
      basis of this method.

PMID- 22853561
TI  - Impact of sputum gross appearance and volume on smear positivity of pulmonary
      tuberculosis: a prospective cohort study.
AB  - BACKGROUND: Although checking specimen quality upon sputum collection for acid
      fast smear of suspected tuberculosis (TB) cases is recommended, this procedure is
      based on expert opinion. The purpose of this study was to elucidate the impact of
      sputum gross appearance and volume on smear positivity among patients with
      suspected pulmonary TB, according to sex. METHODS: From November 2010 through
      June 2011, we enrolled consecutive patients suspected to have active pulmonary
      TB. The association of sputum gross appearance and volume with smear positivity,
      along with other variables possibly affecting smear positivity such as symptoms,
      disease extent, and cavity on chest radiograph, were investigated. RESULTS: Among
      2,439 patients undergoing TB examination, 170 (113 men, 57 women) with active
      pulmonary TB were enrolled. They submitted 492 sputa. There were 73 smear
      positive patients (42.9%) and 164 smear-positive sputa (33.3%). While gross
      appearance was associated with smear positivity in both sexes (purulent or blood
      tinged sputum (rather than mucoid sputum or saliva); odds ratio (OR), 2.05, 95%
      confidence interval (CI), 1.21-3.47 in men; OR, 2.78, 95% CI, 1.23-6.26 in
      women), the amount of sputum specimens was associated with smear positivity in
      only female patients (>=4 ml versus <4 ml; OR, 4.96, 95% CI, 1.98-12.37).
      CONCLUSIONS: Sputum gross appearance and volume were associated with smear
      positivity. A volume of 4 ml seems to be the the minimum sputum volume acceptable
      for smear microscopy in females suspected of TB. Those suspected of TB should be
      encouraged to expectorate grossly qualified sputum specimens.

PMID- 22853564
TI  - Development and validation of QuEChERS method for estimation of
      chlorantraniliprole residue in vegetables.
AB  - An easy, simple and efficient analytical method was standardized and validated
      for the estimation of residues of chlorantraniliprole in different vegetables
      comprising brinjal, cabbage, capsicum, cauliflower, okra, and tomato. QuEChERS
      method was used for the extraction and cleanup of chlorantraniliprole residues on
      these vegetables. Final clear extracts of ethyl acetate were concentrated under
      vacuum and reconstituted into high performance liquid chromatograph (HPLC) grade
      acetonitrile, and residues were estimated using HPLC equipped with PDA detector
      system, C(18) column and confirmed by liquid chromatograph mass spectrometer (LC
      MS/MS), and high performance thin layer chromatograph (HPTLC). HPLC grade
      acetonitrile:water (80:20, v/v) was used as mobile phase @ 0.4 mL/min.
      Chlorantraniliprole presented distinct peak at retention time of 9.82 min.
      Consistent recoveries ranging from 85% to 96% for chlorantraniliprole were
      observed when samples were spiked at 0.10, 0.25, 0.50, and 1.00 mg/kg levels. The
      limit of quantification of this method was worked out to be 0.10 mg/kg.

PMID- 22853565
TI  - Common future and personal responsibilities: a comparison between Italian and
      Burundian students.
AB  - The political, social, and cultural history of a nation modulates the
      representations of rights and duties. The aim of this research is to compare
      students from two countries (Italy and Burundi) in terms of how they define their
      rights and duties. In the two countries, there are differences both in the legal
      protection of fundamental rights and in regard to material conditions, which in
      turn ensure the effectiveness of rights. Focus groups structured around nine
      questions were conducted in Burundi and in Italy. The discussions with Italian
      and Burundian students showed some clear differences. Although both groups speak
      of rights as something to be safeguarded and something that everyone is born
      with, Italian students do not recognize the complementarity of rights and duties
      and consider the latter simply as a limit and an obstacle to individual
      enhancement. On the contrary, Burundian adolescents seem more aware of their
      personal responsibilities and their role in protecting human rights. 

PMID- 22853618
TI  - Transport in nanoribbon interconnects obtained from graphene grown by chemical
      vapor deposition.
AB  - We study graphene nanoribbon (GNR) interconnects obtained from graphene grown by
      chemical vapor deposition (CVD). We report low- and high-field electrical
      measurements over a wide temperature range, from 1.7 to 900 K. Room temperature
      mobilities range from 100 to 500 cm(2).V(-1).s(-1), comparable to GNRs from
      exfoliated graphene, suggesting that bulk defects or grain boundaries play little
      role in devices smaller than the CVD graphene crystallite size. At high-field,
      peak current densities are limited by Joule heating, but a small amount of
      thermal engineering allows us to reach ~2 * 10(9) A/cm(2), the highest reported
      for nanoscale CVD graphene interconnects. At temperatures below ~5 K, short GNRs
      act as quantum dots with dimensions comparable to their lengths, highlighting the
      role of metal contacts in limiting transport. Our study illustrates opportunities
      for CVD-grown GNRs, while revealing variability and contacts as remaining future
      challenges.

PMID- 22853566
TI  - Transcriptomic and physiological responses to fishmeal substitution with plant
      proteins in formulated feed in farmed Atlantic salmon (Salmo salar).
AB  - BACKGROUND: Aquaculture of piscivorous fish is in continual expansion resulting
      in a global requirement to reduce the dependence on wild caught fish for
      generation of fishmeal and fish oil. Plant proteins represent a suitable protein
      alternative to fish meal and are increasingly being used in fish feed. In this
      study, we examined the transcriptional response of Atlantic salmon (Salmo salar)
      to a high marine protein (MP) or low fishmeal, higher plant protein replacement
      diet (PP), formulated to the same nutritional specification within previously
      determined acceptable maximum levels of individual plant feed materials. RESULTS:
      After 77 days of feeding the fish in both groups doubled in weight, however
      neither growth performance, feed efficiency, condition factor nor organ indices
      were significantly different. Assessment of histopathological changes in the
      heart, intestine or liver did not reveal any negative effects of the PP diet.
      Transcriptomic analysis was performed in mid intestine, liver and skeletal
      muscle, using an Atlantic salmon oligonucleotide microarray (Salar_2, Agilent
      4x44K). The dietary comparison revealed large alteration in gene expression in
      all the tissues studied between fish on the two diets. Gene ontology analysis
      showed, in the mid intestine of fish fed PP, higher expression of genes involved
      in enteritis, protein and energy metabolism, mitochondrial activity/kinases and
      transport, and a lower expression of genes involved in cell proliferation and
      apoptosis compared to fish fed MP. The liver of fish fed PP showed a lower
      expression of immune response genes but a higher expression of cell proliferation
      and apoptosis processes that may lead to cell reorganization in this tissue. The
      skeletal muscle of fish fed PP vs MP was characterized by a suppression of
      processes including immune response, energy and protein metabolism, cell
      proliferation and apoptosis which may reflect a more energy efficient tissue.
      CONCLUSIONS: The PP diet resulted in significant effects on transcription in all
      the 3 tissues studied. Despite of these alterations, we demonstrated that high
      level of plant derived proteins in a salmon diet allowed fish to grow with equal
      efficiency as those on a high marine protein diet, and with no difference in
      biometric quality parameters.

PMID- 22853620
TI  - Profiling the careers of Thoroughbred horses racing in Australia between 2000 and
      2010.
AB  - REASONS FOR PERFORMING STUDY: Research investigating trends in racehorse careers
      require a benchmark for accurate comparison. Currently little whole population
      data exists for horses racing in Australia. OBJECTIVES: To determine the range
      and variation in career length and number of career starts for horses racing in
      Australia. To document and provide evidence regarding the current differences
      between the sexes for career length and careers starts. METHODS: Racing data were
      collected for Thoroughbreds over a 10-year period. Career length, number of
      career starts and spells per year were evaluated. Statistical analyses were
      performed using the statistical package R. RESULTS: A total of 2,782,774
      performance records yielded career information for 164,046 horses. Median career
      length and number of career starts for the population were 14.7 months and 10
      starts, respectively. Significant differences (P<0.001) were present between the
      sexes for all career outcomes. Between 2000 and 2010, the percentage of
      Thoroughbreds racing in Australia with careers longer than 12, 24, 36 and 48
      months was 56.65, 32.35, 16.66 and 7.74, respectively. CONCLUSIONS AND POTENTIAL
      RELEVANCE: Clear differences in career outcomes exist between intact males,
      females and geldings racing in Australia. Future research should be conscious of
      these differences when analysing population data.

PMID- 22853619
TI  - Multi-center randomized double-blind controlled clinical study of chemotherapy
      combined with or without traditional Chinese medicine on quality of life of
      postoperative non-small cell lung cancer patients.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) is a widely applied complementary
      therapy for cancer patients. It can reduce the chemical drugs induced toxic
      effects to improve the quality of life (QOL). This study applies the highest
      quality of clinical trial methodology to examine the role of TCM in improving QOL
      of postoperative non-small-cell lung cancer patients. METHODS AND DESIGN: This
      study is a multi-center, randomized, placebo-controlled, double-blind trial. Four
      hundred eighty patients will be recruited into seven different research centers
      in China. These patients that meet the inclusion criteria will be randomized into
      either a treatment group or a placebo group. Each group will receive treatments
      of 3-weekly chemotherapy with TCM or placebo for four cycles. The primary outcome
      will involve the evaluation of QOL and the secondary outcome assessments will
      include two-year disease-free survival rate and disease-free survival. Other
      efficacy assessments are changes of TCM symptoms and toxicity. Side effects and
      safety profile of the therapy would be evaluated at the same time. The
      investigators expect that TCM therapy combined with chemotherapy is superior to
      chemotherapy solely in terms of QOL improvement and disease-free survival
      extension. "Intention-to-treat" analysis will include all randomized
      participants. DISCUSSION: The results from the clinical trial will provide
      evidence for the effectiveness of chemotherapy combined with or without TCM in
      QOL of postoperative NSCLC patients. TRIAL REGISTRATION: Clinical Trials.gov
      (Identifier: NCT01441752).

PMID- 22853621
TI  - Synthesis and screening of antibacterial and antifungal activity of 5-chloro-1,3
      benzoxazol-2(3 h)-one derivatives.
AB  - BACKGROUND: An antibacterial is a substance that either kills bacteria or slows
      their growth. Antifungal are the agents that use drugs for treatment of fungal
      infections. 5-Chloro-1,3-benzoxazol-2(3 H)-one (5-Chloro Benzoxazolinone)
      contains an azole ring structure. Numbers of azole compounds are reported as
      antibacterial and antifungal agents. Benzoxazolinones naturally occur in plants.
      They play a role as defense compounds against bacteria, fungi, and insects.
      RESULTS: In this article, synthesis of six Benzoxazolinone derivatives with
      various substituents is presented. Benzoxazolinone substituted with p
      aminobenzoic acids and sulphanilamide derivatives. The above both substituents
      are reported as potent antimicrobial agents. Attachment with azole leads to
      increase its potency. The other substituents are 2,4-dichlorobezylchloride. The
      same rings are found in miconazole and this may lead to increase its antifungal
      activity. Fluconazole also contains triazole moiety and triazole is having other
      numbers of activity like antimicrobial, anti-inflammatory, local anesthetic,
      antiviral, anticancer, antimalarial, etc. Here, there is a substitution for azole
      ring at 5-Chloro position which might increase antibacterial and antifungal
      activity. The synthesis and interpretation of six final compounds and three
      intermediates are presented in this article. Synthesis of 5-Chloro
      Benzoxazolinone derivatives substituted with Halogenated rings, sulfonated and
      benzylated derivatives and azole derivatives. There is a synthesis of P2A, P2B,
      P4A, P4B, P5A, and P6A compounds and their structures were characterized by UV
      Visible, IR, MASS spectroscopy, and NMR spectroscopy. CONCLUSIONS: The
      antibacterial activity of all six compounds is measured against various Gram
      positive and Gram-negative bacteria and against fungi. Compounds P4A and P4B have
      good antibacterial and antifungal activity, half of the Ampicillin and
      Cephalexin. P4A, P4B, P6A have good activity against Staphylococcus aureus and
      Escherichia coli. Compound P2B has good antifungal activity, half of the
      Miconazole against Candida albicans. P2A, P2B, P5A, P6A have almost equal
      antibacterial activity.

PMID- 22853622
TI  - Exploring the expression of depression and distress in aboriginal men in central
      Australia: a qualitative study.
AB  - BACKGROUND: Despite being at heightened risk of developing mental illness, there
      has been little research into the experience of depression in Australian
      Aboriginal populations. This study aimed to outline the expression, experience,
      manifestations and consequences of emotional distress and depression in
      Aboriginal men in central Australia. METHODS: Utilizing a grounded theory
      approach, in depth semi-structured interviews were conducted with 22
      theoretically sampled young, middle aged and senior Aboriginal men and
      traditional healers. Analysis was conducted by a single investigator using
      constant comparison methods. RESULTS: Depressive symptoms were common and
      identifiable, and largely consistent with symptom profiles seen in non-Aboriginal
      groups. For Aboriginal men, depression was expressed and understood as primarily
      related to weakness or injury of the spirit, with a lack of reference to
      hopelessness and specific somatic complaints. The primary contributors to
      depression related to the loss of connection to social and cultural features of
      Aboriginal life, cumulative stress and marginalisation. CONCLUSIONS: Depression
      and depressive symptomatology clearly exists in Aboriginal men, however its
      determinants and expression differ from mainstream populations. Emotions were
      understood within the construction of spirit, Kurunpa, which was vulnerable to
      repetitive and powerful negative social forces, loss, and stress across the life
      course, and served to frame the physical and emotional experience and expression
      of depression.

PMID- 22853624
TI  - A C-H borylation approach to Suzuki-Miyaura coupling of typically unstable 2
      heteroaryl and polyfluorophenyl boronates.
AB  - A method for the synthesis of biaryls and heterobiaryls from arenes and
      haloarenes without the intermediacy of unstable boronic acids is described.
      Pinacol boronate esters that are analogous to unstable boronic acids are formed
      in high yield by iridium-catalyzed C-H borylation of heteroarenes and
      fluoroarenes. These boronates are stable in the solid state or in solution and
      can be generated and used in situ. They couple with aryl halides in the presence
      of simple palladium catalysts, providing a convenient route to biaryl and
      heteroaryl products that have been challenging to prepare via boronic acids.

PMID- 22853623
TI  - Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin
      resistant MCF7 cells is associated with survivin stabilization.
AB  - BACKGROUND: Cisplatin resistance is a serious problem in cancer treatment. To
      overcome it, alternative approaches including virotherapy are being pursued. One
      of the candidates for anticancer virotherapy is the Newcastle disease virus
      (NDV). Even though NDV's oncolytic properties in various cancer cells have been
      widely reported, information regarding its effects on cisplatin resistant cancer
      cells is still limited. Therefore, we tested the oncolytic efficacy of a strain
      of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line.
      METHODS: Cisplatin-resistant cell line (MCF7-CR) was developed from the MCF7
      human breast adenocarcinoma cell line by performing a seven-cyclic exposure to
      cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS)
      analysis and immunoblotting were used to measure cell viability and viral protein
      expression, respectively. Production of virus progeny was then assessed by using
      the plaque assay technique. RESULTS: Infection of a mass population of the MCF7
      CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi),
      comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR
      became less susceptible to NDV killing. This reduced susceptibility led to
      increased viral protein synthesis and virus progeny production. The reduction was
      also associated with a prolonged cell survival via stabilization of the survivin
      protein. CONCLUSIONS: Our findings showed for the first time, the involvement of
      survivin in the reduction of NDV-induced oncolysis in a subpopulation of
      cisplatin-resistant cells. This information will be important towards improving
      the efficacy of NDV as an anticancer agent in drug resistant cancers.

PMID- 22853625
TI  - Syntheses and magnetic properties study of isostructural BiM2BP2O10 (M = Co, Ni)
      containing a quasi-1D linear chain structure.
AB  - We present here the structures and magnetism of two quasi-1D linear chain
      compounds of BiM(2)BP(2)O(10) (M = Co, Ni), which were synthesized by traditional
      solid-state reactions for the first time. Two title compounds crystallize in the
      monoclinic system with space group P2(1)/c and feature novel 3D structures with a
      linear chain structure of {MO(6)}(n) further connected by [BP(2)O(10)](7-)
      anionic groups. The results of magnetic property measurements evidence the
      antiferromagnetic properties of both compounds in low magnetic field and a field
      dependent metamagnetic transition from the antiferromagnetic to ferromagnetic
      ground state of the BiCo(2)BP(2)O(10) complex.

PMID- 22853626
TI  - A novel dual material mouthguard for patients with dental implants.
AB  - AIM: Dental implant-supported reconstructions demonstrate significantly less
      physiological flexibility for loading and traumatic forces compared with a normal
      dentition because of their rigid integration with the adjacent bone. Ethylene
      vinyl acetate (EVA) material has become widely accepted as a mouthguard material;
      however, many studies indicate the necessity of improving the impact absorption
      ability by considering the design and developing new materials. The aim of this
      study was to compare the shock-absorbing ability of a novel dual component
      material comprising EVA and porous rubber with that of EVA alone. MATERIALS AND
      METHODS: Three groups of samples were tested: Group 1 = EVA (thickness, 4 mm),
      Group 2 = type 1 material (2-mm thick porous rubber sheet sandwiched between two
      sheets of 1-mm thick EVA sheets), and Group 3 = type 2 material (1-mm thick
      porous rubber sheet sandwiched between EVA sheets with 1 and 2-mm thickness,
      respectively). Shock absorption was determined by means of a hammer impact
      testing device equipped with strain gauge, accelerator, and load cell. RESULTS:
      The value of shock-absorbing ability of group 2 (40.6 +/- 12.5%) was
      significantly higher than those of group 1 (15.6 +/- 2.1%) and group 3 (21.2 +/-
      9.2%). The material with thicker rubber sheet showed significantly higher shock
      absorbing ability compared with that of the material with thinner rubber sheet.
      CONCLUSIONS: The novel dual material was superior to conventional EVA material in
      shock-absorbing ability depending on the thickness of porous rubber, and it may
      be potentially effective as mouthguard material, in particular, for patients
      wearing implant-supported constructions.

PMID- 22853627
TI  - Comparison between stem cells harvested from wet and dry lipoaspirates.
AB  - Adipose-derived stem cells (ASC) are usually isolated from lipoaspirates, but it
      is not known if the anesthetic solution injected into adipose tissue affects cell
      yield and functions. Two different samples were drawn from the abdominal region
      of female subjects. In the first, a physiological solution containing
      lidocaine/adrenaline was injected (wet liposuction, WL), while in the
      contralateral area, the sample was collected without injecting any solution (dry
      liposuction, DL). The aspirates were processed to investigate the yield of the
      stromal-vascular fraction (SVF) cells and ASC frequency, growth rate, apoptosis,
      and differentiation potential. The solid dried mass of fresh WL isolates was
      lower than that of DL isolates (p < 0.01) due to the presence, in the former, of
      a liquid solution. As a consequence, the amount of WL-SVF cells was 18.7% lower
      than those obtained from DL (p < 0.01); this difference was also observed under
      culture conditions. In addition, the number of colony-forming unit-fibroblasts
      (CFU-Fs) obtained from 1 * 10(3) SVF cells was 25.5% lower in WL-aspirates than
      DL-aspirates (p < 0.05) owing, at least in part, to the observed presence of ASC
      [corrected] in the liquid solution of the WL isolates. After WL and DL, no
      differences were observed in ASC growth rate, apoptosis, or differentiation
      potential toward adipogenic, osteogenic, and endothelial cell lineages. In
      conclusion, WL yields about 40% fewer ASC than DL due to the combined effect of
      tissue dilution and the reduced frequency of ASC in the SVF. The main biological
      features of ASC are suitable for cell-based therapies.

PMID- 22853628
TI  - Food-grade submicrometer particles from salts prepared using ethanol-in-oil
      mixtures.
AB  - A simple method for preparing food-grade particles in the submicrometer range of
      ethanol soluble salts using ethanol-in-oil (E/O) mixtures is described. Salts
      CaCl2.2H2O and MgCl2.6H2O were dissolved in ethanol that subsequently was mixed
      with a medium-chain triglyceride oil phase. It was found that type and
      concentration of salt have a significant influence on the miscibility of ethanol
      and oil phase and on the stability of E/O mixtures. The ethanol phase was
      evaporated from the mixture at elevated temperatures, and salt particles with
      dimensions in the submicrometer range (6-400 nm) remained suspended in the oil
      phase. It was found that the concentration of salt and volume fraction of ethanol
      in MCT oil have a significant influence on the size distribution of salt
      particles. The size of CaCl2 and MgCl2 submicrometer particles was ascertained by
      scanning electron microscopy and dynamic light scattering. 

PMID- 22853630
TI  - Probable late lyme disease: a variant manifestation of untreated Borrelia
      burgdorferi infection.
AB  - BACKGROUND: Lyme disease, a bacterial infection with the tick-borne spirochete
      Borrelia burgdorferi, can cause early and late manifestations. The category of
      probable Lyme disease was recently added to the CDC surveillance case definition
      to describe patients with serologic evidence of exposure and physician-diagnosed
      disease in the absence of objective signs. We present a retrospective case series
      of 13 untreated patients with persistent symptoms of greater than 12 weeks
      duration who meet these criteria and suggest a label of 'probable late Lyme
      disease' for this presentation. METHODS: The sample for this analysis draws from
      a retrospective chart review of consecutive, adult patients presenting between
      August 2002 and August 2007 to the author (JA), an infectious disease specialist.
      Patients were included in the analysis if their current illness had lasted
      greater than or equal to 12 weeks duration at the time of evaluation. RESULTS:
      Probable late Lyme patients with positive IgG serology but no history of previous
      physician-documented Lyme disease or appropriate Lyme treatment were found to
      represent 6% of our heterogeneous sample presenting with >= 12 weeks of symptom
      duration. Patients experienced a range of symptoms including fatigue, widespread
      pain, and cognitive complaints. Approximately one-third of this subset reported a
      patient-observed rash at illness onset, with a similar proportion having been
      exposed to non-recommended antibiotics or glucocorticosteroid treatment for their
      initial disease. A clinically significant response to antibiotics treatment was
      noted in the majority of patients with probable late Lyme disease, although post
      treatment symptom recurrence was common. CONCLUSIONS: We suggest that patients
      with probable late Lyme disease share features with both confirmed late Lyme
      disease and post-treatment Lyme disease syndrome. Physicians should consider the
      recent inclusion of probable Lyme disease in the CDC Lyme disease surveillance
      criteria when evaluating patients, especially in patients with a history
      suggestive of misdiagnosed or inadequately treated early Lyme disease. Further
      studies are warranted to delineate later manifestations of Lyme disease and to
      quantify treatment benefit in this population.

PMID- 22853631
TI  - The effect of attentional scope on spatial relation processing: a case study.
AB  - Patient NC showed impairment on several tasks making use of coordinate spatial
      information, while categorical processing was at control level. Her assessment of
      local and global features of visual stimuli indicated that she had a local bias
      of attention, whereas controls showed a global bias. Her problems with coordinate
      tasks can be explained by this reduced global attentional focus. These findings
      confirm previous reports suggesting that the processing of categorical spatial
      relations benefits from a small scope of attention, whereas a relatively large
      scope of attention enhances coordinate spatial relation processing. 

PMID- 22853629
TI  - Cognitive vulnerabilities and depression versus other psychopathology symptoms
      and diagnoses in early adolescence.
AB  - We examined the concurrent associations between multiple cognitive
      vulnerabilities to depression featured in hopelessness theory, Beck's theory, and
      response styles theory and depressive symptoms and diagnoses in a sample of early
      adolescents. We also examined the specificity of these cognitive vulnerabilities
      to depression versus anxiety and externalizing psychopathology, controlling for
      co-occurring symptoms and diagnoses. Male and female, Caucasian and African
      American, 12- to 13-year-old adolescents were assessed in a cross-sectional
      design. Cognitive vulnerabilities of hopelessness, inferential style, rumination,
      and self-referent information processing were assessed with self-reports and
      behavioral tasks. Symptoms and diagnoses of depressive, anxiety, and
      externalizing disorders were assessed with self-report questionnaires and
      diagnostic interviews. Hopelessness exhibited the greatest specificity to
      depressive symptoms and diagnoses, whereas negative inferential styles,
      rumination, and negative self-referent information processing were associated
      with both depressive and anxiety symptoms and diagnoses and, in some cases, with
      externalizing disorders. Consistent with cognitive theories of depression,
      hopelessness, negative inferential styles, rumination, and negative self-referent
      information processing were associated with depressive symptoms and diagnoses.
      However, with the exception of hopelessness, most of the remaining cognitive
      vulnerabilities were not specific to depression. With further maturation of our
      sample, these cognitive vulnerabilities may become more specific to depression as
      cognitive styles further develop and consolidate, the rates of depression
      increase, and individuals' presentations of psychopathology become more
      differentiated.

PMID- 22853632
TI  - Explaining between-group differences in performance on timing tasks.
AB  - The article discusses interpretation of between-group differences in performance
      on timing tasks. First, it is shown that differences in internal clock "pacemaker
      speed" cannot normally be used as a coherent explanation of obtained effects,
      even if such differences in pacemaker speed exist. Secondly, it is shown how, in
      theory, modelling of performance on commonly used timing tasks like bisection and
      temporal generalization can illuminate between-group effects. Thirdly, the
      article discusses some examples of such modelling from published work and shows
      how some between-group differences--for example, between children of different
      ages, or between patients and controls--have been explained. Finally, some
      ambiguities in modelling are discussed--for example, the fact that different
      explanations of differences in performance on timing tasks between groups may be
      difficult or impossible to distinguish in practice.

PMID- 22853633
TI  - Determination of nickel in food samples by flame atomic absorption spectroscopy
      after preconcentration and microextraction based ionic liquids using full
      factorial and central composite design.
AB  - In this research, a microextraction technique based on ionic liquids (ILs) termed
      in situ solvent formation microextraction (ISFME) was used for determination of
      nickel in solutions. 1-(2-pyridylazo)-2-naphtol (PAN) was chosen as a complexing
      agent. After preconcentration, the settled IL-phase was dissolved in 50 MUL of
      ethanol and aspirated into the flame atomic absorption spectrometer (FAAS) using
      a home-made microsample introduction system. Injection of 50 MUL volumes of
      analyte into an air-acetylene flame provided very sensitive spike-like and
      reproducible signals. ISFME is based on phase separation phenomenon of ionic
      liquids in aqueous solutions. This method is simple and rapid for extraction and
      preconcentration of metal ions from food samples and can be applied for the
      sample solutions containing very high concentrations of salt. Furthermore, this
      technique is much safer in comparison with the organic solvent extraction because
      of using ionic liquid. The effective parameters such as amount of IL, salt
      effect, concentration of the chelating agent and ion pairing agent were inspected
      by a full factorial design to identify important parameters and their
      interactions. Next, a central composite design was applied to obtain optimum
      point of the important parameters. Under the optimum conditions, the calibration
      graph was linear over the range of 2 to 80 ng/mL. The limit of detection and
      relative standard deviation (n= 6) were 0.6 ng/mL and 2%, respectively.

PMID- 22853634
TI  - Folic acid supplementation prevents the changes in hepatic promoter methylation
      status and gene expression in intrauterine growth-retarded piglets during early
      weaning period.
AB  - During intrauterine life, genome interacts with maternal signals to influence the
      mRNA expression levels of specific genes persistently by regulating DNA
      methylation status. The objective of this study was to examine the responses of
      glucocorticoid receptor (GR), peroxisome proliferator-activated receptor alpha
      and gamma (PPARalpha and PPARgamma) promoter methylation, mRNA expression of
      genes involved in energy metabolism and metabolite concentrations of intrauterine
      growth-retarded (IUGR) piglets to dietary folic acid supplementation. According
      to a 2 * 2 factorial arrangement, 16 IUGR and 16 normal birth weight (NBW)
      piglets were fed a basal diet or a basal diet supplemented with 5 mg/kg of folic
      acid from weaning (day 14) to day 35 of age. Triglycerides in hepatic tissue and
      plasma were significantly elevated in control diets-fed IUGR piglets compared
      with NBW piglets but were decreased by dietary folic acid supplementation.
      Hepatic mRNA expression levels of GR, PPARalpha, PPARgamma, fatty acid synthase
      and phosphoenolpyruvate carboxykinase (PEPCK) in IUGR piglets fed a control diet
      were significantly higher than that in NBW piglets, and promoter methylation
      status of GR, PPARalpha and PPARgamma in IUGR piglets was reduced significantly
      compared with NBW piglets. However, the changes in gene expression and DNA
      methylation status of IUGR piglets were reversed by dietary folic acid
      supplementation. Hepatic DNA methyltransferase activity was greater with dietary
      folic acid supplementation regardless of birth weight. Taken together, these
      results demonstrated that folic acid supplementation during early period of life
      could prevent the changes of promoter methylation status and gene expressions in
      the liver of IUGR piglets. 

PMID- 22853636
TI  - Left ventricular geometry and diastolic function in the hypertensive heart:
      impact of age.
AB  - BACKGROUND AND AIM: The impact of aging on the relationship between left
      ventricular (LV) mass/geometry and diastolic function as assessed by updated
      echocardiographic methods, such as tissue Doppler, is poorly defined. We
      investigated this issue in a cohort of hypertensive patients. METHODS: A total of
      660 hypertensives (mean age 65 +/- 13 years, 48% men) with preserved LV systolic
      function underwent a comprehensive echo-Doppler examination for routine clinical
      indications. For the present analysis, the subjects have been divided in two age
      groups (<65 or >=65 years). RESULTS: Overall, 61% of subjects fulfilled the
      criteria for LVH, 18% for left atrial (LA) enlargement and 11% for altered LV
      filling index. Concentric LV geometry was 1.4-fold higher in older hypertensives
      than in younger counterparts; also the prevalence of LA enlargement and altered
      LV filling was 2.0- and 1.9-fold higher in the former group, respectively. In
      older hypertensives, at variance from younger ones, neither LV mass nor relative
      wall thickness (RWT), a continuous index of LV geometry, were independently
      correlated to conventional as well as tissue Doppler LV diastolic indexes.
      CONCLUSIONS: Our findings suggest the relationship between cardiac hypertrophy
      and diastolic function in hypertensive subjects is affected by aging-associated
      factors unrelated to the amount of LV mass as assessed by standard
      echocardiography.

PMID- 22853635
TI  - Gender and the treatment of immune-mediated chronic inflammatory diseases:
      rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational
      study.
AB  - BACKGROUND: Rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and
      psoriasis are immune-mediated inflammatory diseases with similarities in
      pathophysiology, and all can be treated with similar biological agents. Previous
      studies have shown that there are gender differences with regard to disease
      characteristics in RA and IBD, with women generally having worse scores on pain
      and quality of life measurements. The relationship is less clear for psoriasis.
      Because treatment differences between men and women could explain the
      dissimilarities, we investigated gender differences in the disease
      characteristics before treatment initiation and in the biologic treatment
      prescribed. METHODS: Data on patients with RA or IBD were collected from two
      registries in which patients treated with biologic medication were enrolled.
      Basic demographic data and disease activity parameters were collected from a time
      point just before the initiation of the biologic treatment. For patients with
      psoriasis, the data were taken from the 2010 annual report of the Swedish
      Psoriasis Register for systemic treatment, which included also non-biologic
      treatment. For all three diseases, the prescribed treatment and disease
      characteristics were compared between men and women. RESULTS: In total, 4493
      adult patients were included in the study (1912 with RA, 131 with IBD, and 2450
      with psoriasis). Most of the treated patients with RA were women, whereas most of
      the patients with IBD or psoriasis were men. There were no significant
      differences between men and women in the choice of biologics. At treatment start,
      significant gender differences were seen in the subjective disease measurements
      for both RA and psoriasis, with women having higher (that is, worse) scores than
      men. No differences in objective measurements were found for RA, but for
      psoriasis men had higher (that is, worse) scores for objective disease activity
      measures. A similar trend to RA was seen in IBD. CONCLUSIONS: Women with RA or
      psoriasis scored significantly higher on subjective, but not on objective,
      disease activity measures than men, and the same trend was seen in IBD. This
      indicates that at the same level of treatment, the disease has a greater effect
      in women. These findings might suggest that in all three diseases, subjective
      measures are discounted to some extent in the therapeutic decision-making
      process, which could indicate undertreatment in female patients.

PMID- 22853638
TI  - Adsorption of nitrate on kaolinite surfaces: a theoretical study.
AB  - The interactions of HNO(3) and NO(3)(-) with kaolinite surfaces are important in
      the reaction of airborne clay mineral particles with atmospheric trace gases.
      Theoretical calculations at the B3LYP/6-311++G(d,p) level were performed on
      surface clusters of HNO(3) on kaolinite, on monodentate, on bidentate, and on two
      bridged complex structures of NO(3)(-) on kaolinite and on gas phase and solvated
      NO(3)(-). The results are compatible with the ranges assigned in the literature
      for NO(3)(-) on mineral surfaces for the frequency of the vibrational symmetric
      stretches (nu(1)) and for the low-frequency branch of the asymmetric stretches
      (nu(3)), with slightly higher frequencies reported for the bridged models. For
      the higher-frequency branch of the asymmetric stretches measured on kaolinite
      (Angelini et al.), our calculations match the assigned values for the monodentate
      surface complex, while predicting an inverse assignment for the frequencies of
      the bidentate and bridged complexes.

PMID- 22853637
TI  - Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate
      induced chromosomal aberrations in mouse bone marrow cells.
AB  - BACKGROUND: Ayurveda, the traditional Indian system of medicine has given great
      emphasis to the promotion of health. Rasayana is one of the eight branches of
      Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas
      have immuno-modulatory, antioxidant and antitumor functions, however, the
      genotoxic potential and modulation of DNA repair of many rasayanas have not been
      evaluated. METHODS: The present study assessed the role of Brahmarasayana (BR) on
      Ethyl methanesulfonate (EMS)-and Methyl methanesulfonate (MMS)-induced
      genotoxicity and DNA repair in in vivo mouse test system. The mice were orally
      fed with BR (5 g or 8 mg / day) for two months and 24 h later EMS or MMS was
      given intraperitoneally. The genotoxicity was analyzed by chromosomal
      aberrations, sperm count, and sperm abnormalities. RESULTS: The results have
      revealed that BR did not induce significant chromosomal aberrations when compared
      to that of the control animals (p >0.05). On the other hand, the frequencies of
      chromosomal aberrations induced by EMS (240 mg / kg body weight) or MMS (125 mg /
      kg body weight) were significantly higher (p<0.05) to that of the control group.
      The treatment of BR for 60 days and single dose of EMS or MMS on day 61, resulted
      in significant (p <0.05) reduction in the frequency of chromosomal aberrations in
      comparison to EMS or MMS treatment alone, indicating a protective effect of BR.
      Constitutive base excision repair capacity was also increased in BR treated
      animals. CONCLUSION: The effect of BR, as it relates to antioxidant activity was
      not evident in liver tissue however rasayana treatment was observed to increase
      constitutive DNA base excision repair and reduce clastogenicity. Whilst, the
      molecular mechanisms of such repair need further exploration, this is the first
      report to demonstrate these effects and provides further evidence for the role of
      brahmarasayana in the possible improvement of quality of life.

PMID- 22853639
TI  - A polymer surfactant corona dynamically replaces water in solvent-free protein
      liquids and ensures macromolecular flexibility and activity.
AB  - The observation of biological activity in solvent-free protein-polymer surfactant
      hybrids challenges the view of aqueous and nonaqueous solvents being unique
      promoters of protein dynamics linked to function. Here, we combine elastic
      incoherent neutron scattering and specific deuterium labeling to separately study
      protein and polymer motions in solvent-free hybrids. Myoglobin motions within the
      hybrid are found to closely resemble those of a hydrated protein, and motions of
      the polymer surfactant coating are similar to those of the hydration water,
      leading to the conclusion that the polymer surfactant coating plasticizes protein
      structures in a way similar to hydration water.

PMID- 22853641
TI  - Method: low-cost delivery of the cotton leaf crumple virus-induced gene silencing
      system.
AB  - BACKGROUND: We previously developed a virus-induced gene silencing (VIGS) vector
      for cotton from the bipartite geminivirusCotton leaf crumple virus (CLCrV). The
      original CLCrV VIGS vector was designed for biolistic delivery by a gene gun.
      This prerequisite limited the use of the system to labs with access to biolistic
      equipment. Here we describe the adaptation of this system for delivery by
      Agrobacterium (Agrobacterium tumefaciens). We also describe the construction of
      two low-cost particle inflow guns. RESULTS: The biolistic CLCrV vector was
      transferred into two Agrobacterium  binary plasmids. Agroinoculation of the
      binary plasmids into cotton resulted in silencing and GFP expression comparable
      to the biolistic vector. Two homemade low-cost gene guns were used to
      successfully inoculate cotton (G. hirsutum)  and N. benthamiana with either the
      CLCrV VIGS vector or the Tomato golden mosaic virus (TGMV) VIGS vector
      respectively. CONCLUSIONS: These innovations extend the versatility of CLCrV
      based VIGS for analyzing gene function in cotton. The two low-cost gene guns make
      VIGS experiments affordable for both research and teaching labs by providing a
      working alternative to expensive commercial gene guns.

PMID- 22853640
TI  - Cell-adhesive and cell-repulsive zwitterionic oligopeptides for micropatterning
      and rapid electrochemical detachment of cells.
AB  - In this study, we describe the development of oligopeptide-modified cell culture
      surfaces from which adherent cells can be rapidly detached by application of an
      electrical stimulus. An oligopeptide, CGGGKEKEKEK, was designed with a terminal
      cysteine residue to mediate binding to a gold surface via a gold-thiolate bond.
      The peptide forms a self-assembled monolayer through the electrostatic force
      between the sequence of alternating charged glutamic acid (E) and lysine (K)
      residues. The dense and electrically neutral oligopeptide zwitterionic layer of
      the modified surface was resistant to nonspecific adsorption of proteins and
      adhesion of cells, while the surface was altered to cell adhesive by the addition
      of a second oligopeptide (CGGGKEKEKEKGRGDSP) containing the RGD cell adhesion
      motif. Application of a negative electrical potential to this gold surface
      cleaved the gold-thiolate bond, leading to desorption of the oligopeptide layer,
      and rapid (within 2 min) detachment of virtually all cells. This approach was
      applicable not only to detachment of cell sheets but also for transfer of cell
      micropatterns to a hydrogel. This electrochemical approach of cell detachment may
      be a useful tool for tissue-engineering applications.

PMID- 22853642
TI  - Design and baseline characteristics of the Short bouTs of Exercise for
      Preschoolers (STEP) study.
AB  - BACKGROUND: Most preschool centers provide two 30-min sessions of gross
      motor/outdoor playtime per preschool day. Within this time frame, children
      accumulate most of their activity within the first 10 min. This paper describes
      the design and baseline participant characteristics of the Short bouTs of
      Exercise for Preschoolers (STEP) study. The STEP study is a cluster randomized
      controlled study designed to examine the effects of short bouts of structured
      physical activity (SBS-PA) implemented within the classroom setting as part of
      designated gross-motor playtime on during-school physical activity (PA) in
      preschoolers. METHODS/DESIGN: Ten preschool centers serving low-income families
      were randomized into SBS-PA versus unstructured PA (UPA). SBS-PA schools were
      asked to implement age-appropriate 10 min structured PA routines within the
      classroom setting, twice daily, followed by 20 min of usual unstructured
      playtime. UPA intervention consisted of 30 min of supervised unstructured free
      playtime twice daily. Interventions were implemented during the morning and
      afternoon designated gross-motor playtime for 30 min/session, five days/week for
      six months. Outcome measures were between group difference in during-preschool PA
      (accelerometers and direct observation) over six-months. Ten preschool centers,
      representing 34 classrooms and 315 children, enrolled in the study. The average
      age and BMI percentile for the participants was 4.1 +/- 0.8 years and 69th
      percentile, respectively. Participants spent 74% and 6% of their preschool day
      engaged in sedentary and MVPA, respectively. DISCUSSION: Results from the STEP
      intervention could provide evidence that a PA policy that exposes preschoolers to
      shorter bouts of structured PA throughout the preschool day could potentially
      increase preschoolers' PA levels.

PMID- 22853643
TI  - A coarse-grained model for synergistic action of multiple enzymes on cellulose.
AB  - BACKGROUND: Degradation of cellulose to glucose requires the cooperative action
      of three classes of enzymes, collectively known as cellulases. Endoglucanases
      randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing
      beta-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze
      glycosidic bonds in a processive manner releasing cellobiose units. Then, beta
      glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action
      of these enzymes is essential for efficient digestion of cellulose. Experiments
      show that as hydrolysis proceeds and the cellulose substrate becomes more
      heterogeneous, the overall degradation slows down. As catalysis occurs on the
      surface of crystalline cellulose, several factors affect the overall hydrolysis.
      Therefore, spatial models of cellulose degradation must capture effects such as
      enzyme crowding and surface heterogeneity, which have been shown to lead to a
      reduction in hydrolysis rates. RESULTS: We present a coarse-grained stochastic
      model for capturing the key events associated with the enzymatic degradation of
      cellulose at the mesoscopic level. This functional model accounts for the
      mobility and action of a single cellulase enzyme as well as the synergy of
      multiple endo- and exo-cellulases on a cellulose surface. The quantitative
      description of cellulose degradation is calculated on a spatial model by
      including free and bound states of both endo- and exo-cellulases with explicit
      reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages)
      and corresponding reaction rates. The dynamical evolution of the system is
      simulated by including physical interactions between cellulases and cellulose.
      CONCLUSIONS: Our coarse-grained model reproduces the qualitative behavior of
      endoglucanases and exoglucanases by accounting for the spatial heterogeneity of
      the cellulose surface as well as other spatial factors such as enzyme crowding.
      Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails.
      This model constitutes a critical step towards testing hypotheses and
      understanding approaches for maximizing synergy and substrate properties with a
      goal of cost effective enzymatic hydrolysis.

PMID- 22853644
TI  - Return to use and performance following exploratory celiotomy for colic in
      horses: 195 cases (2003-2010).
AB  - REASONS FOR PERFORMING STUDY: There are few objective data on return to use and
      performance in horses following colic surgery. OBJECTIVE: To investigate return
      to functional use of horses following colic surgery and factors associated with a
      negative outcome. METHODS: The North Carolina State University Equine Colic
      Database was reviewed for horses that underwent exploratory celiotomy for colic
      (2003-2010). Horses were excluded from the study if they survived <6 months, had
      no intended use preoperatively, or if further data were not available at
      attempted follow-up. Information retrieved included history, background, use, and
      selected pre-, intra-, and post operative factors. Telephone interviews were used
      to obtain follow-up data. Logistic regression was used to investigate
      associations between clinical data and outcome, reported as odds ratios with a
      95% confidence interval and corresponding P value. RESULTS: Of patients surviving
      to 6 months, 133/195 (68%) were performing their intended use and 85/156 (54%)
      were at or above preoperative performance. At one year, 145/190 (76%) horses were
      performing their intended use and 101/153 (66%) were at or above preoperative
      performance. Animals were significantly less likely to return to use/performance
      if they had a previous celiotomy, stall rest for an orthopaedic condition, a
      nonstrangulating lesion type, incisional hernia, diarrhoea or laminitis.
      CONCLUSIONS: The overall prognosis for return to use and performance following
      colic surgery is fair to good. Multiple pre- and post operative factors may
      affect the likelihood of return to use and performance. POTENTIAL RELEVANCE:
      Targeted owner education regarding preoperative lameness, post operative
      rehabilitation and treatment for complications, such as incisional hernioplasty,
      may help inform owners about their horse's potential for return to use and
      performance following colic surgery.

PMID- 22853645
TI  - The detection of pfcrt and pfmdr1 point mutations as molecular markers of
      chloroquine drug resistance, Pahang, Malaysia.
AB  - BACKGROUND: Malaria is still a public health problem in Malaysia with chloroquine
      (CQ) being the first-line drug in the treatment policy of uncomplicated malaria.
      There is a scarcity in information about the magnitude of Plasmodium falciparum
      CQ resistance. This study aims to investigate the presence of single point
      mutations in the P. falciparum chloroquine-resistance transporter gene (pfcrt) at
      codons 76, 271, 326, 356 and 371 and in P. falciparum multi-drug resistance-1
      gene (pfmdr1) at codons 86 and 1246, as molecular markers of CQ resistance.
      METHODS: A total of 75 P. falciparum blood samples were collected from different
      districts of Pahang state, Malaysia. Single nucleotide polymorphisms in pfcrt
      gene (codons 76, 271, 326, 356 and 371) and pfmdr1 gene (codons 86 and 1246) were
      analysed by using mutation-specific nested PCR and restriction fragment length
      polymorphism (PCR-RFLP) methods. RESULTS: Mutations of pfcrt K76T and pfcrt R371I
      were the most prevalent among pfcrt gene mutations reported by this study; 52%
      and 77%, respectively. Other codons of the pfcrt gene and the positions 86 and
      1246 of the pfmdr1 gene were found mostly of wild type. Significant associations
      of pfcrt K76T, pfcrt N326S and pfcrt I356T mutations with parasitaemia were also
      reported. CONCLUSION: The high existence of mutant pfcrt T76 may indicate the low
      susceptibility of P. falciparum isolates to CQ in Peninsular Malaysia. The
      findings of this study establish baseline data on the molecular markers of P.
      falciparum CQ resistance, which may help in the surveillance of drug resistance
      in Peninsular Malaysia.

PMID- 22853646
TI  - Transcriptome sequencing of Eucalyptus camaldulensis seedlings subjected to water
      stress reveals functional single nucleotide polymorphisms and genes under
      selection.
AB  - BACKGROUND: Water stress limits plant survival and production in many parts of
      the world. Identification of genes and alleles responding to water stress
      conditions is important in breeding plants better adapted to drought. Currently
      there are no studies examining the transcriptome wide gene and allelic expression
      patterns under water stress conditions. We used RNA sequencing (RNA-seq) to
      identify the candidate genes and alleles and to explore the evolutionary
      signatures of selection. RESULTS: We studied the effect of water stress on gene
      expression in Eucalyptus camaldulensis seedlings derived from three natural
      populations. We used reference-guided transcriptome mapping to study gene
      expression. Several genes showed differential expression between control and
      stress conditions. Gene ontology (GO) enrichment tests revealed up-regulation of
      140 stress-related gene categories and down-regulation of 35 metabolic and cell
      wall organisation gene categories. More than 190,000 single nucleotide
      polymorphisms (SNPs) were detected and 2737 of these showed differential allelic
      expression. Allelic expression of 52% of these variants was correlated with
      differential gene expression. Signatures of selection patterns were studied by
      estimating the proportion of nonsynonymous to synonymous substitution rates
      (Ka/Ks). The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that
      most of the genes are under purifying selection. Among the positively selected
      genes (Ka/Ks > 1.5) apoptosis and cell death categories were enriched. Of the 287
      positively selected genes, ninety genes showed differential expression and 27
      SNPs from 17 positively selected genes showed differential allelic expression
      between treatments. CONCLUSIONS: Correlation of allelic expression of several
      SNPs with total gene expression indicates that these variants may be the cis
      acting variants or in linkage disequilibrium with such variants. Enrichment of
      apoptosis and cell death gene categories among the positively selected genes
      reveals the past selection pressures experienced by the populations used in this
      study.

PMID- 22853647
TI  - Reproducibility of Corneal Graft Thickness measurements with COLGATE in patients
      who have undergone DSAEK (Descemet Stripping Automated Endothelial Keratoplasty).
AB  - BACKGROUND: The CorneaL GrAft Thickness Evaluation (COLGATE) system was recently
      developed to facilitate the evaluation of corneal graft thickness from OCT
      images. Graft thickness measurement can be a surrogate indicator for detecting
      graft failure or success. The purpose of this study was to determine the
      reproducibility of the COLGATE system in measuring DSAEK graft area between two
      observers. METHODS: This was a prospective case series in which 50 anterior
      segment OCT images of patients who had undergone DSAEK in either eye were
      analysed. Two observers (MW, AC) independently obtained the image analysis for
      the graft area using both semi automated and automated method. One week later,
      each observer repeated the analysis for the same set of images. Bland-Altman
      analysis was performed to analyze inter and intra observer agreement. RESULTS:
      There was strong intraobserver correlation between the 2 semi automated readings
      obtained by both observers. (r = 0.936 and r = 0.962). Intraobserver ICC for
      observer 1 was 0.936 (95% CI 0.890 to 0.963) and 0.967 (95% CI 0.942 to 0.981)
      for observer 2. Likewise, there was also strong interobserver correlation (r =
      0.913 and r = 0.969). The interobserver ICC for the first measurements was 0.911
      (95% CI 0.849 to 0.949) and 0.968 (95% CI 0.945 to 0.982) for the second. There
      was statistical difference between the automatic and the semi automated readings
      for both observers (p = 0.006, p = 0.003). The automatic readings gave
      consistently higher values than the semi automated readings especially in thin
      grafts. CONCLUSION: The analysis from the COLGATE programme can be reproducible
      between different observers. Care must be taken when interpreting the automated
      analysis as they tend to over estimate measurements.

PMID- 22853650
TI  - A peculiar prevalence of p values just below .05.
AB  - In null hypothesis significance testing (NHST), p values are judged relative to
      an arbitrary threshold for significance (.05). The present work examined whether
      that standard influences the distribution of p values reported in the psychology
      literature. We examined a large subset of papers from three highly regarded
      journals. Distributions of p were found to be similar across the different
      journals. Moreover, p values were much more common immediately below .05 than
      would be expected based on the number of p values occurring in other ranges. This
      prevalence of p values just below the arbitrary criterion for significance was
      observed in all three journals. We discuss potential sources of this pattern,
      including publication bias and researcher degrees of freedom.

PMID- 22853651
TI  - Dynamic deuterium magic angle spinning NMR of a molecule grafted at the inner
      surface of a mesoporous material.
AB  - Deuterium magic angle spinning (MAS) NMR is used to study the dynamics of an
      organic molecule, N-[triethoxysilylpropyl]acetamide-d3, grafted at the inner
      surface of the mesoporous silica material, MCM-41. The grafted molecule has a
      deuterated methyl group at its free terminus to monitor its local mobility
      through changes in its dynamic (2)H-MAS NMR spectrum. Different spectra were
      recorded as a function of temperature from two different water containing
      samples. Observation shows that a major part of the grafted molecule remains
      static, irrespective of the temperature and hydration state of the sample,
      whereas the rest shows spectral changes indicative of a two-site jump motion of
      the methyl groups. Experimental observations were substantiated using molecular
      dynamic (MD) simulations of the grafted molecule. Subsequently, the MD results
      corroborate a model for the grafted molecules experiencing an exchange between
      two conformations consistent with the analysis of the (2)H-MAS NMR spectra. 

PMID- 22853649
TI  - The relationship between sleep and wake habits and academic performance in
      medical students: a cross-sectional study.
AB  - BACKGROUND: The relationship between the sleep/wake habits and the academic
      performance of medical students is insufficiently addressed in the literature.
      This study aimed to assess the relationship between sleep habits and sleep
      duration with academic performance in medical students. METHODS: This study was
      conducted between December 2009 and January 2010 at the College of Medicine, King
      Saud University, and included a systematic random sample of healthy medical
      students in the first (L1), second (L2) and third (L3) academic levels. A self
      administered questionnaire was distributed to assess demographics, sleep/wake
      schedule, sleep habits, and sleep duration. Daytime sleepiness was evaluated
      using the Epworth Sleepiness Scale (ESS). School performance was stratified as
      "excellent" (GPA >= 3.75/5) or "average" (GPA <3.75/5). RESULTS: The final
      analysis included 410 students (males: 67%). One hundred fifteen students (28%)
      had "excellent" performance, and 295 students (72%) had "average" performance.
      The "average" group had a higher ESS score and a higher percentage of students
      who felt sleepy during class. In contrast, the "excellent" group had an earlier
      bedtime and increased TST during weekdays. Subjective feeling of obtaining
      sufficient sleep and non-smoking were the only independent predictors of
      "excellent" performance. CONCLUSION: Decreased nocturnal sleep time, late
      bedtimes during weekdays and weekends and increased daytime sleepiness are
      negatively associated with academic performance in medical students.

PMID- 22853652
TI  - Interactions in supramolecular complexes involving arenes: experimental studies.
AB  - The process of learning by doing has fueled supramolecular chemistry and, more
      specifically, the understanding of noncovalent aromatic interactions in synthetic
      and natural systems. The preparation of new host molecules and the investigation
      of their complexations have produced many insights into significant noncovalent
      binding mechanisms. In this Account, we attempt to discuss significant binding
      contributions involving aromatic units and their practical applications. We use
      typical examples from our group and the literature, but this Account is not a
      comprehensive view of the field. Other than systems with saturated frameworks,
      host compounds based on arenes offer better controlled conformations and active
      interactions with many guest molecules. Because of their fluorescent properties,
      larger aryl systems are particularly suitable for sensors. The noncovalent
      interactions observed with different supramolecular complexes can be compared and
      exploited for interactions with biopolymers such as nucleic acids. Complexes
      formed with cyclophanes have been a constant source of inspiration for
      understanding noncovalent forces and their use for the design of functional
      supramolecular systems. Other than cyclodextrins or ionophores, which occur in
      nature, arene-based macrocycles are synthetic and provide more opportunities for
      structural variations than other macrocycles. These derivatives allow researchers
      to study and to exploit an unusually broad variety of binding mechanisms in both
      aqueous and organic media. Systematic analyses of complexes with different
      substituents and structures in solution, based also on flat aromatic systems such
      as porphyrins, can lead to a consistent picture of the noncovalent forces that
      dominate in these systems. These studies have elucidated attractive interactions
      between many heteroatoms and pi systems including cyclopropanes . Through
      systematic analysis of the equilibrium measurements one can derive binding free
      energy increments for different interactions. The increments are usually additive
      and provide predictive tools for the design of new supramolecular systems,
      benchmarks for computational approaches, and an aid for drug design. In aqueous
      media, the major noncovalent forces between different aryl systems or between
      arenes and heteroatoms of larger polarizibility are dispersive, and hydrophobic
      forces play a minor role. In several examples, we show that electrostatic forces
      also contribute significantly if donor and acceptor groups show complimentarity.
      In early investigations, researchers found cation-pi and, to a lesser degree,
      anion-pi interactions with several cyclophanes in systems where the host or the
      guest molecules bear charges in an orientation that facilitates contact between
      charged and aryl portions of the molecules. In supramolecular complexes, hydrogen
      bonding effects are usually only visible in apolar media, but very strong
      acceptors such as phenolate anions can also work in water. To facilitate
      potential applications, researchers have primarily developed water-soluble, arene
      containing receptors through the implementation of permanent charges.
      Supramolecular complexes that mimic enzymes can also rely on aryl interactions.
      Examples in this Account illustrate that the conformation of host-guest complexes
      may differ significantly between the solid and solution state, and suitable
      spectroscopic methods are needed to observe and control these conformations.

PMID- 22853648
TI  - SEB-3, a CRF receptor-like GPCR, regulates locomotor activity states, stress
      responses and ethanol tolerance in Caenorhabditis elegans.
AB  - The CRF (corticotropin-releasing factor) system is a key mediator of the stress
      response. Alterations in CRF signaling have been implicated in drug craving and
      ethanol consumption. The development of negative reinforcement via activation of
      brain stress systems has been proposed as a mechanism that contributes to alcohol
      dependence. Here, we isolated a gain-of-function allele of seb-3, a CRF receptor
      like GPCR in Caenorhabditis elegans, providing an in vivo model of a
      constitutively activated stress system. We also characterized a loss-of-function
      allele of seb-3 and showed that SEB-3 positively regulates a stress response that
      leads to an enhanced active state of locomotion, behavioral arousal and tremor.
      SEB-3 also contributed to acute tolerance to ethanol and to the development of
      tremor during ethanol withdrawal. Furthermore, we found that a specific CRF(1) 
      receptor antagonist reduced acute functional tolerance to ethanol in mice. These
      findings demonstrate functional conservation of the CRF system in responses to
      stress and ethanol in vertebrates and invertebrates.

PMID- 22853653
TI  - Stimulation of cadaverine production by foodborne pathogens in the presence of
      Lactobacillus, Lactococcus, and Streptococcus spp.
AB  - The effect of Lactobacillus plantarum (FI8595), Lactococcus lactis subsp.
      cremoris MG 1363), Lactococcus lactis subsp. lactis (IL 1403), and Streptococcus
      thermophilus on cadaverine and other biogenic amine production by foodborne
      pathogens was investigated lysine decarboxylase broth. Both of lactic acid
      bacteria and foodborne pathogens used (especially Staphylococcus aureus, E. coli,
      Lc. lactis subsp. lactis and Lb. plantarum) had an ability to convert aminoacids
      into biogenic amine. The conversion of lysine into cadaverine was the highest
      (167.11 mg/L) by Lactobacillus spp. Gram-positive bacteria generally had a
      greater ability to produce cadaverine with corresponding value of 46.26, 53.76,
      and 154.54 mg/L for Enterococcus faecalis, S. aureus, and Listeria monocytogenes,
      respectively. Significant variations on biogenic amine production were observed
      in the presence of lactic acid bacteria strains (P < 0.05). The role of lactic
      acid bacteria on biogenic amine production by foodborne pathogens varied
      depending on strains and specific amine. Cadaverine accumulation by
      Enterobactericeae was increased in the presence of lactic acid bacteria strains
      except for St. thermophilus, which induced 2-fold lower cadaverine production by
      S. Paratyphi A. Lc. lactis subsp. lactis and Lc. lactis subsp. cremoris induced
      10-fold higher increases in histamine for E. coli and K. pneumoniae,
      respectively. Lactic acid bacteria resulted in strong increases in cadaverine
      production by P. aeruginosa, although remarkable decreases were observed for
      histamine, spermidine, dopamine, agmatine, and TMA in the presence of lactic acid
      bacteria in lysine decarboxylase broth . The result of the study showed that
      amine positive lactic acid bacteria strains in fermented food led to significant
      amine accumulation by contaminant bacteria and their accumulation in food product
      may be controlled by the use of proper starters with amine-negative activity.

PMID- 22853688
TI  - Short synthesis of diamide-linked sucrose macrocycles.
AB  - A convenient route to macrocyclic diamide-linked macrocyclic derivatives with a
      sucrose scaffold is presented. Reaction of sucrose based amines (o- and m-) with
      acid dichlorides afforded the monomeric macrocycles in excellent yields, while
      reaction of the p-amines also provided dimeric products.

PMID- 22853689
TI  - Genetic variants of LPIN1 indicate an association with Type 2 diabetes mellitus
      in a Chinese population.
AB  - AIMS: Metabolic disorders are independent risk factors for the development of
      Type 2 diabetes. The aim of the study is to test the association of LPIN1
      variants with Type 2 diabetes and clinical characteristics in large samples of
      the Chinese population. METHODS: In the first stage, 15 single nucleotide
      polymorphisms within the LPIN1 region were selected and genotyped in 3700 Chinese
      Han participants. In the second stage, the single nucleotide polymorphisms
      showing significant association or trends towards association were genotyped in
      an additional 3122 samples for replication. Meta-analyses and genotype-phenotype
      association studies were performed after combining the data from the two stages.
      RESULTS: In the first stage, we detected that rs16857876 was significantly
      associated with Type 2 diabetes with an odds ratio of 0.806 (95% CI 0.677-0.958,
      P = 0.015), while rs11695610 showed a trend with Type 2 diabetes (odds ratio
      0.846, 95% CI 0.709-1.009, P = 0.062). In the second stage, a similar effect of
      rs11695610 on Type 2 diabetes was observed (odds ratio 0.849, 95% CI 0.700-1.030,
      P = 0.096). The meta-analyses combining the information from the two stages
      showed a significant effect of rs11695610 on Type 2 diabetes with an odds ratio
      of 0.847 (95% CI 0.744-0.965, P = 0.012). Finally, the phenotype-genotype
      association analyses showed that rs11695610 was associated with 2-h plasma
      glucose (P = 0.040) and triglyceride levels (P = 0.034). CONCLUSIONS: Our data
      implied that common single nucleotide polymorphisms within the LPIN1 region were
      associated with Type 2 diabetes and metabolic traits in the Chinese population.

PMID- 22853691
TI  - Identification of Tau and SOD1 gene mutation in a small Chinese Han pedigree of
      adult amyotrophic lateral sclerosis.
AB  - We report the clinical profile, and a brief investigation of SOD1 and Tau gene
      mutation from a small Chinese Han pedigree of adults with amyotrophic lateral
      sclerosis (ALS), which consisted of 32 familial members with 6 affected
      individuals spanning five generations, and presenting autosomal dominant genetic
      mode. The mean age of onset was 36.6 +/- 15.9 years, and disease duration was 6
      months to more than 5 years, the average survival was 16.1 +/- 8.2 months. There
      were 5 patients with an early disease onset, rapid progressive course and short
      survival, and 1 patient with late onset, slow progressive course and long
      survival in the kindred. ALS patients began to suffer with weakness and muscle
      atrophy in one side of a lower extremity, which then spread to the upper
      extremity, the opposite side and bulbar muscles. All patients had spinal onset
      type. Muscle stretch reflexes were absent or weak in the upper limbs and
      accentuation in the lower limbs; pathological signs in the lower limbs were
      positive. Electromyography disclosed ongoing denervation muscle potentials in the
      four extremities. Brain and spinal MRI did not show any abnormal signal. A 5
      exons mutation of SOD1 in all affected individuals was identified using SSCP.
      Polymorphisms of partial risk regions in 3',5' UTR, and in introns 9, 10, 11, 12
      of the Tau gene in the affected and normal family members and in 70 healthy
      controls were examined by DNA sequencing. Routine exons mutation of SOD1 was not
      detected, but one single nucleotide polymorphism of A to G at 138278 at 3' UTR of
      the Tau gene was shown to significantly over-express in fALS familial members. 

PMID- 22853692
TI  - Highlights from the 2012 International Symposium on HIV & Emerging Infectious
      Diseases (ISHEID): from cART management to the search of an HIV cure.
AB  - The 2012 International Symposium on HIV and Emerging Infectious Diseases
      (ISHEID) provided a forum for investigators to hear the latest research
      developments in the clinical management of HIV and HCV infections as well as HIV
      1 reservoirs and cure research. Combined anti-retroviral therapy (c-ART) has had
      a profound impact on the disease prognosis of individuals living with HIV-1
      infection. However, although these anti-retroviral regimens are able to reduce
      plasma viremia to below the limits of detection for sustained periods of time,
      there is a rapid recrudescence in plasma viremia if treatment is interrupted.
      Therefore, despite this potent anti-retroviral suppression, HIV-1 is able to
      persist within the infected individual. The main 2012 ISHEID theme was, hence
      "searching for an HIV cure". In this report we not only give details on this main
      topic of the 2012 ISHEID but also summarize what has been discussed in the areas
      of HIV epidemiology, access to care, antiretroviral therapy management and recent
      progress in the therapy of HCV infection in patients with HIV.

PMID- 22853690
TI  - Diabetic angiopathy and angiogenic defects.
AB  - Diabetes is one of the most serious health problems in the world. A major
      complication of diabetes is blood vessel disease, termed angiopathy, which is
      characterized by abnormal angiogenesis. In this review, we focus on angiogenesis
      abnormalities in diabetic complications and discuss its benefits and drawbacks as
      a therapeutic target for diabetic vascular complications. Additionally, we
      discuss glucose metabolism defects that are associated with abnormal angiogenesis
      in atypical diabetic complications such as cancer.

PMID- 22853693
TI  - The effects of house moves during early childhood on child mental health at age 9
      years.
AB  - BACKGROUND: Residential mobility is common in families with young children;
      however, its impact on the social development of children is unclear. We examined
      associations between the number, timing and type of house moves in childhood and
      child behaviour problems using data from an ongoing longitudinal study. METHODS:
      Complete data on residential mobility and child behaviour was available for 403
      families. Three aspects of mobility were considered: (a) number of house moves
      from birth to <2 years, 2 to <5 years and 5 to 9 years; (b) lifetime number of
      house moves; and (c) moves associated with different housing trajectories
      characterized by changes in housing tenure. The primary outcomes were
      internalizing and externalizing behaviour problems at 9 years derived from
      Achenbach's Child Behaviour Checklist. Linear regression analyses were used to
      investigate the effect of the housing variables on internalizing and
      externalizing behaviour problem scores with adjustment for a range of
      sociodemographic and household covariates. RESULTS: Moving house >=2 times before
      2 years of age was associated with an increased internalizing behaviour score at
      age 9 years. This association remained after adjustment for sociodemographic and
      household factors. There was no association between increased residential
      mobility in other time periods and internalizing behaviour, or mobility in any
      period and externalizing behaviour. There was no effect of lifetime number of
      moves, or of an upwardly or downwardly mobile housing trajectory. However, a
      housing trajectory characterized by continuous rental occupancy was associated
      with an increased externalizing behaviour score. CONCLUSIONS: These findings may
      suggest that there is a sensitive period, in the first few years of life, in
      which exposure to increased residential mobility has a detrimental effect on
      mental health in later childhood.

PMID- 22853694
TI  - Revisiting the association between pornography use and risky sexual behaviors:
      the role of early exposure to pornography and sexual sensation seeking.
AB  - Among the suggested problems and harms associated with widespread pornography use
      among young people, risky sexual behaviors have been frequently mentioned. To
      further explore this public health concern, this article analyzed sexual
      sensation seeking (SSS) as a potential confounder of the association between
      pornography use and sexual risks using data collected in 2010 from a population
      based sample of young Croatian adults aged 18 to 25 (n = 1,005). Significant, but
      small, correlations were found between the indicators of pornography use (age at
      first exposure, frequency of use in the past 12 months, and personal importance
      of pornography) and sexual risk taking. However, in a multivariate analysis, only
      age at first exposure to pornography remained a significant, albeit weak,
      predictor of sexual risk taking among both women and men. SSS, defined as the
      dispositional tendency toward the impulsive pursuit of sexual arousal and
      stimulation, neither confounded nor moderated this association. Overall, the
      findings do not support the notion that pornography use is substantially
      associated with sexual risk taking among young adults, but suggest that early
      exposure to sexually explicit material and high SSS are additive risk factors for
      sexual risk taking.

PMID- 22853695
TI  - Heterometallic Co(III)4Fe(III)2 Schiff base complex: structure, electron
      paramagnetic resonance, and alkane oxidation catalytic activity.
AB  - The heterometallic complex [Co(4)Fe(2)OSae(8)].4DMF.H(2)O (1) was synthesized by
      one-pot reaction of cobalt powder with iron chloride in a dimethylformamide
      solution of salicylidene-2-ethanolamine (H(2)Sae) and characterized by single
      crystal X-ray diffraction analysis, magnetic measurements, high frequency
      electron paramagnetic resonance (HF-EPR), and Mossbauer spectroscopies. The
      exchange coupling in the Fe(III)-Fe(III) pair is of antiferromagnetic behavior
      with J/hc = -190 cm(-1). The HF-EPR spectra reveal an unusual pattern with a
      hardly detectable triplet signal of the Fe(III) dimer. The magnitude of D (ca.
      13.9 cm(-1)) was found to be much larger than in related dimers. The catalytic
      investigations disclosed an outstanding activity of 1 toward oxidation of
      cycloalkanes with hydrogen peroxide, under mild conditions. The most efficient
      system showed a turnover number (TON) of 3.57 * 10(3) with the concomitant
      overall yield of 26% for cyclohexane, and 2.28 * 10(3)/46%, respectively, for
      cyclooctane. A remarkable turnover frequency (TOF) of 1.12 * 10(4) h(-1) (the
      highest initial rate W(0) = 3.5 * 10(-4) M s(-1)) was achieved in oxidation of
      cyclohexane. Kinetic experiments and selectivity parameters led to the conclusion
      that hydroxyl radicals are active (attacking C-H bonds) species. Kinetic and
      electrospray ionization mass spectrometry (ESI-MS) data allowed us to assume that
      the trinuclear heterometallic particle [Co(2)Fe(Sae)(4)](+), originated from 1 in
      solution, could be responsible for efficient generation of hydroxyl radicals from
      hydrogen peroxide.

PMID- 22853696
TI  - Fibroblasts regulate osteoblasts through gap junctional communication.
AB  - BACKGROUND AIMS: Fibroblasts are present in most tissues of the body, playing an
      active role in the regulation of homeostasis in such tissues. While fibroblast
      heterotypic interactions are acknowledged in the regeneration of tissues such as
      skin and periodontal ligament, their role in bone regeneration is far from being
      understood. We hypothesized that fibroblasts could influence osteoblasts, and as
      connexin 43 is the predominant connexin in both cell types, we speculated that
      those heterotypic interactions could occur through gap junctional communication
      (GjC). METHODS: Direct co-cultures of human mesenchymal stromal cell (hMSC)
      derived osteoblasts and human dermal fibroblasts (hDFb) were established in the
      presence and absence of the GjC inhibitor alpha-glycyrrhetinic acid.
      Communication between osteoblasts and hDFb via GjC was verified by transference
      of the gap junction-permeable dye calcein-AM. Cell proliferation was assessed by
      dsDNA quantification, while osteogenic differentiation was evaluated by measuring
      alkaline phosphatase (ALP) activity and the expression of osteogenic markers by
      real-time polymerase chain reaction (PCR). RESULTS: The amount of calcein-AM
      transferred between the different cell types decreased when alpha-glycyrrhetinic
      acid was used. While the proliferation of the hMSC-derived osteoblasts was not
      affected by the presence of the hDFb, the level of osteogenic markers such as ALP
      activity and osteocalcin in transcripts in osteoblasts was severely diminished.
      This effect was partially reversed by adding alpha-glycyrrhetinic acid to the co
      cultures. CONCLUSIONS: The results strongly suggest that fibroblasts regulate
      osteoblast behavior partially through GjC. This information could be critical for
      predicting the outcome of strategies aimed at promoting bone regeneration as, for
      example, in bone tissue-engineering approaches.

PMID- 22853697
TI  - Decreased estimated glomerular filtration rate (eGFR) is not an independent risk
      factor of arterial stiffness in Chinese women.
AB  - Recent studies suggest that decreased estimated glomerular filtration rate (eGFR)
      and uric acid (UA) may be independent risk factors for arterial stiffness (AS).
      As serum UA level is linked to renal function, we hypothesize that decreased eGFR
      may be not an independent risk factor of AS, but may be related to UA level. In
      this study, we aimed to validate this hypothesis in a large community-based
      Chinese population. A total of 13,899 people were selected from the
      Cardiovascular Risk Survey (CRS) from October 2007 to March 2010. Pulse wave
      velocity (PWV) was calculated using the established methods. The relationships
      between eGFR, fasting blood glucose (FBG), UA and PWV were analyzed with
      multivariate linear regression. We found that PWV was significantly correlated to
      FBG (r = 0.173, p < 0.001) and UA (r = 0.177, p < 0.001), and inversely
      correlated to eGFR (r = - 0.161, p < 0.001). A multivariable regression analysis
      revealed that FBG (beta = 0.056, p < 0.001) and UA (beta = 0.039, p < 0.001), but
      not eGFR (beta = - 0.011, p = 0.062) were significantly related to elevation of
      PWV. In women, eGFR was not an independent risk factor of AS with progressively
      decreasing renal function (all p > 0.05). However, in men, eGFR was associated
      with PWV in subjects with eGFR < 60 ml/min/1.73 m(2). Our results suggest that
      decreased eGFR is not independently associated with AS in Chinese women.

PMID- 22853698
TI  - In ovo leptin administration accelerates post-hatch muscle growth and changes
      myofibre characteristics, gene expression and enzymes activity in broiler
      chickens.
AB  - To evaluate the effect of maternal leptin on muscle growth, we injected 0 MUg
      (control, CON), 0.5 MUg (low leptin dose, LL) or 5.0 MUg (high leptin dose, HL)
      of recombinant murine leptin dissolved in 100 MUl of PBS into the albumen of
      broiler eggs prior to incubation. The newly hatched chicks were all raised under
      the same conditions until 21 days of age (D21), when body weight was measured and
      samples of gastrocnemius muscle were collected and weighed. Myosin ATPase
      staining was applied to identify myofibre types and measure the cross-sectional
      area (CSA) of myofibres. Real-time PCR was performed to quantify leptin receptor
      (LEPR), insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), growth
      hormone receptor (GHR) and myostatin (MSTN) mRNA expression in the gastrocnemius
      muscle. The activity of calpains (CAPNs) in the gastrocnemius muscle was measured
      using a quantitative fluorescence detection kit. Male chickens treated with both
      high and low doses of leptin had significantly higher (p < 0.05) body weight on
      D21. The high leptin significantly increased the CSA (p < 0.05) of gastrocnemius
      muscle in male chickens, which coincided with a 93% increase (p < 0.05) in IGF-1
      mRNA expression. Likewise, the LL dose increased the weight of gastrocnemius
      muscle in male chickens (p < 0.05), which was accompanied by a 41% down
      regulation (p < 0.05) of MSTN mRNA expression and a decreased activity of CAPNs.
      However, all these changes were not observed in female chickens. The proportion
      of myofibre types did not altered. No significant change was detected for LEPR
      and GHR mRNA expression. These results indicate that in ovo leptin treatment
      affects skeletal muscle growth in chickens in a dose-dependent and sex-specific
      manner. The altered expression of IGF-1, MSTN mRNA and activity of CAPNs in
      skeletal muscle may be responsible for such effects. 

PMID- 22853699
TI  - A cross-sectional study of sub-clinical Plasmodium falciparum infection in HIV-1
      infected and uninfected populations in Mozambique, South-Eastern Africa.
AB  - BACKGROUND: Plasmodium falciparum and HIV-1 infection cause substantial morbidity
      and mortality in sub-Saharan Africa. Increasing evidence suggests these two
      pathogens interact negatively when infecting the same individual. METHODS: A
      cross-sectional study among HIV-1 infected and uninfected populations was
      recruited in Mocuba and Maputo, Mozambique to determine the prevalence of sub
      clinical malarial parasitaemia using light microscopy and a nested PCR assay.
      RESULTS: The prevalence of sub-clinical P. falciparum parasitaemia was low in
      Maputo, whether determined by microscopy (0.4%) or PCR (1.9%), but substantially
      higher in Mocuba (7.6 and 14.7%, respectively). Nested PCR detected nearly 70%
      more cases of sub-clinical parasitaemia than microscopy, but differences occur by
      locality. HIV-1 infected persons were more likely to be sub-clinically
      parasitaemic than HIV-1 uninfected individuals recruited from the same geographic
      areas. Trimethoprim-sulphamethoxazole use did not substantially reduce sub
      clinical parasitaemia. CONCLUSIONS: Dried blood spots are a convenient and
      sensitive technique for detecting sub-clinical infection with P. falciparum by
      nested PCR. Prevalence of P. falciparum is substantially lower in Maputo where
      malaria control programmes have been more active than in the rural town of
      Mocuba. In Mocuba, among those presenting for HIV-1 counseling and testing, the
      prevalence of P. falciparum is substantially higher in those who test positive
      for HIV-1 than those without HIV-1 infection. The clinical implications of sub
      clinical P. falciparum infection among HIV-1 infected persons warrant additional
      study.

PMID- 22853700
TI  - Central retinal vein occlusion treated with Ozurdex: a case report and review of
      literature.
AB  - PURPOSE: To describe the retinal changes occurring after Ozurdex((r)) (Ozurdex,
      Allergan, Inc., Irvine, CA) injection and peripheral laser treatment in a case of
      central retinal vein occlusion (CRVO). CASE REPORT: A 51-year-old Caucasian man
      with massive retinal edema (926 MUm) and hand motion visual acuity due to severe
      CRVO was treated early with Ozurdex intravitreal injection. Detailed monthly
      follow-up examinations showed complete resorption of the edema (253 MUm) after 2
      months and a 20/32 visual outcome after 3 months. The patient subsequently
      developed peripheral retinal ischemia accompanied by recurrence of small retinal
      cystoid spaces (295 MUm); therefore, he underwent an associated laser treatment
      on the involved peripheral retina, which led to a recovery in retinal thickness
      (280 MUm). His visual acuity remained stable at 20/32. CONCLUSIONS: Early Ozurdex
      injection in association with late laser photocoagulation was effective in the
      resorption of CRVO macular edema and in restoring reasonably good visual acuity.

PMID- 22853701
TI  - Improvement of quality of life following 6 months of methadone maintenance
      therapy in Malaysia.
AB  - BACKGROUND: Methadone Maintenance Therapy (MMT) is one of the popular choices for
      drug substitution therapy and is fairly new in Malaysia. Aside from its role in
      harm reduction against HIV infection, MMT programme may potentially enhances
      clients' quality of life. This study aims to identify the impact of MMT programme
      on clients' quality of life after 6 months in treatment and to explore factors
      that may be associated with changes in their quality of life. METHODS: In this
      retrospective report review, 122 subjects from 2 government MMT clinics were
      selected from the district of Tampin, Negeri Sembilan, Malaysia. The raw score
      from the WHO Quality of Life questionnaire (WHOQOL-BREF), at baseline and 6
      months after therapy were collected and converted to 0-100 scale form to give
      quality of life scores for four domains; physical, psychological, social
      relationships and environment. Other variables of interest were socio-demography,
      age when joining MMT programme, age and duration of illicit drug use, HIV and
      Hepatitis C status, and the Opiate Treatment Index (OTI) score on drug use,
      sexual and social aspect at the baseline. Statistical analysis used the SPSS
      version 16. RESULTS: There was significant improvement in all four domains of
      quality of life, after 6 months of MMT. The largest improvement was for
      psychological domain (mean score difference 15.54 +/- 20.81). Multivariable
      linear regression analysis showed that, for the physical domain, there was no
      significant predictor. For both the psychological and social domains, having
      tertiary education is a significant predictor for improvement in both aspects of
      quality of life. Negative HIV status is associated with improvement for the
      environment domain. CONCLUSIONS: There was a significant short term improvement
      in the quality of life of MMT clients who stayed in the programme for at least 6
      months in the district of Tampin, Negeri Sembilan, Malaysia.

PMID- 22853702
TI  - Multifunctional role of dextran sulfate sodium for in vivo modeling of intestinal
      diseases.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders
      that affect the gastrointestinal tract of millions of people and continue to
      increase in incidence each year. While several factors have been associated with
      development of IBDs, the exact etiology is unknown. Research using animal models
      of IBDs is beginning to provide insights into how the different factors
      contribute to disease development. Oral administration of dextran sulfate sodium
      (DSS) to mice induces a reproducible experimental colitis that models several
      intestinal lesions associated with IBDs. The murine DSS colitis model can also be
      adapted to quantify intestinal repair following injury. Understanding the
      mechanistic basis behind intestinal repair is critical to development of new
      therapeutics for IBDs because of their chronic relapsing nature. RESULTS: The
      murine DSS colitis model was adapted to provide a system enabling the
      quantification of severe intestinal injury with impaired wound healing or mild
      intestinal injury with rapid restoration of mucosal integrity, by altering DSS
      concentrations and including a recovery phase. We showed that through a novel
      format for presentation of the clinical disease data, the temporal progression of
      intestinal lesions can be quantified on an individual mouse basis. Additionally,
      parameters for quantification of DSS-induced alterations in epithelial cell
      populations are included to provide insights into mechanisms underlying the
      development of these lesions. For example, the use of the two different model
      systems showed that toll-like receptor 9, a nucleic acid-sensing pattern
      recognition receptor, is important for protection only following mild intestinal
      damage and suggests that this model is superior for identifying proteins
      necessary for intestinal repair. CONCLUSIONS: We showed that using a murine DSS
      induced experimental colitis model system, and presenting data in a longitudinal
      manner on a per mouse basis, enhanced the usefulness of this model, and provided
      novel insights into the role of an innate immune receptor in intestinal repair.
      By elucidating the mechanistic basis of intestinal injury and repair, we can
      begin to understand the etiology of IBDs, enabling development of novel
      therapeutics or prophylactics.

PMID- 22853703
TI  - Selection for high alcohol preference drinking in mice results in heightened
      sensitivity and rapid development of acute functional tolerance to alcohol's
      ataxic effects.
AB  - Propensity to develop acute functional (or within session) tolerance to alcohol
      (ethanol) may influence the amount of alcohol consumed, with higher drinking
      associated with greater acute functional tolerance (AFT). The goal of this study
      was to assess this potential correlated response between alcohol preference and
      AFT in second and third replicate lines of mice selectively bred for high (HAP2
      and HAP3) and low (LAP2 and LAP3) alcohol preference drinking. Male and female
      mice were tested for development of AFT on a static dowel task, which requires
      that animals maintain balance on a wooden dowel in order to prevent falling. On
      test day, each mouse received one (1.75 g/kg; Experiment 1) or two (1.75 and 2.0
      g/kg; Experiment 2) injections of ethanol; an initial administration before being
      placed on the dowel and in Experiment 2, an additional administration after the
      first regain of balance on the dowel. Blood samples were taken immediately after
      loss of balance [when blood ethanol concentrations (BECs) were rising] and at
      recovery (during falling BECs) in Experiment 1, and after first and second
      recovery in Experiment 2. It was found that HAP mice fell from the dowel
      significantly earlier and at lower BECs than LAP mice following the initial
      injection of ethanol and were therefore more sensitive to its early effects.
      Furthermore, Experiment 1 detected significantly greater AFT development
      (BECfalling--BECrising) in HAP mice when compared with LAP mice, which occurred
      within ~30 min, supporting our hypothesis. However, AFT was not different between
      lines in Experiment 2, indicating that ~30-60 min following alcohol
      administration, AFT development was similar in both lines. These data show that
      high alcohol drinking genetically associates with both high initial sensitivity
      and very early tolerance to the ataxic effects of ethanol.

PMID- 22853704
TI  - Base-stacking disorder and excited-state dynamics in single-stranded adenine homo
      oligonucleotides.
AB  - Single-stranded adenine homo-oligonucleotides were investigated in aqueous
      solution by femtosecond transient absorption spectroscopy in order to study the
      effect of strand length on the nature and dynamics of excited states formed by UV
      absorption. Global fitting analysis of bleach recovery signals recorded at a
      probe wavelength of 250 nm and pH 7 reveals that the same lifetimes of 2.72 and
      183 ps reproduce the pronounced biexponential decays observed in all (dA)n
      oligomers, containing between 2 and 18 residues. Although the lifetimes are
      invariant, the amplitudes of the short- and long-lived components depend
      sensitively on the number of residues. For example, the 183 ps component
      increases with strand length and is greater for DNA vs RNA single strands with
      the same number of adenines. Inhomogeneous kinetics arising from two classes of
      adenine bases in each oligomer best explains the observations. A subset of
      adenine residues produce short-lived excited states upon excitation, while
      absorption by the remaining adenines yields long-lived excited states that are
      responsible for the long-lived signal. By assuming that each short-lived excited
      state in the oligomer makes the same contribution to the transient absorption
      signal as an excited state of the adenine mononucleotide, the fraction of each
      type of base in the oligomer can be estimated along with the quantum yield of
      long-lived excited states. The fraction of oligonucleotides that yield long-lived
      excited states increases with oligomer length in precisely the same manner as the
      fraction of bases that are found in base stacks. Corroborating evidence that base
      stacking leads to distinct decay channels comes from experiments conducted at low
      pH on (dA)2. Coulombic repulsion between the two protonated bases at pH 2 results
      in open, unstacked conformations causing the long-lived component seen in (dA)2
      at neutral pH to vanish completely. The fast component seen in oligomers with two
      or more bases is assigned to vibrational cooling following ultrafast internal
      conversion to the electronic ground state. This monomer-like decay channel is
      operative for the subset of adenine residues that are either poorly or not at all
      stacked with neighboring bases. This study shows that static base stacking
      disorder fully accounts for the length-dependent transient absorption signals.
      Although absorption likely creates delocalized excitons of unknown spatial
      extent, the results from this study suggest that long-lived excitations in single
      stranded A tracts are already fully localized on no more than two bases no later
      than 1 ps after UV excitation. 

PMID- 22853705
TI  - Setting an agenda for comparative effectiveness systematic reviews in CKD care.
AB  - Systematic reviews comparing the effectiveness of strategies to prevent, detect,
      and treat chronic kidney disease are needed to inform patient care. We engaged
      stakeholders in the chronic kidney disease community to prioritize topics for
      future comparative effectiveness research systematic reviews. We developed a
      preliminary list of suggested topics and stakeholders refined and ranked topics
      based on their importance. Among 46 topics identified, stakeholders nominated 18
      as 'high' priority. Most pertained to strategies to slow disease progression,
      including: (a) treat proteinuria, (b) improve access to care, (c) treat
      hypertension, (d) use health information technology, and (e) implement dietary
      strategies. Most (15 of 18) topics had been previously studied with two or more
      randomized controlled trials, indicating feasibility of rigorous systematic
      reviews. Chronic kidney disease topics rated by stakeholders as 'high priority'
      are varied in scope and may lead to quality systematic reviews impacting practice
      and policy.

PMID- 22853706
TI  - Virtual patients design and its effect on clinical reasoning and student
      experience: a protocol for a randomised factorial multi-centre study.
AB  - BACKGROUND: Virtual Patients (VPs) are web-based representations of realistic
      clinical cases. They are proposed as being an optimal method for teaching
      clinical reasoning skills. International standards exist which define precisely
      what constitutes a VP. There are multiple design possibilities for VPs, however
      there is little formal evidence to support individual design features. The
      purpose of this trial is to explore the effect of two different potentially
      important design features on clinical reasoning skills and the student
      experience. These are the branching case pathways (present or absent) and
      structured clinical reasoning feedback (present or absent). METHODS/DESIGN: This
      is a multi-centre randomised 2 x 2 factorial design study evaluating two
      independent variables of VP design, branching (present or absent), and structured
      clinical reasoning feedback (present or absent).The study will be carried out in
      medical student volunteers in one year group from three university medical
      schools in the United Kingdom, Warwick, Keele and Birmingham. There are four core
      musculoskeletal topics. Each case can be designed in four different ways,
      equating to 16 VPs required for the research. Students will be randomised to four
      groups, completing the four VP topics in the same order, but with each group
      exposed to a different VP design sequentially. All students will be exposed to
      the four designs. Primary outcomes are performance for each case design in a
      standardized fifteen item clinical reasoning assessment, integrated into each VP,
      which is identical for each topic. Additionally a 15-item self-reported
      evaluation is completed for each VP, based on a widely used EViP tool. Student
      patterns of use of the VPs will be recorded.In one centre, formative clinical and
      examination performance will be recorded, along with a self reported pre and post
      intervention reasoning score, the DTI. Our power calculations indicate a sample
      size of 112 is required for both primary outcomes. DISCUSSION: This trial will
      provide robust evidence to support the effectiveness of different designs of
      virtual patients, based on student performance and evaluation. The cases and all
      learning materials will be open access and available on a Creative Commons
      Attribution-Share-Alike license.

PMID- 22853707
TI  - Case management in aftercare of involuntarily committed patients with substance
      abuse. A randomized trial.
AB  - OBJECTIVE: Case management has since the 1970s been widely used to co-ordinate
      services for mental health patients. The methodology has expanded to support
      patients in many different types of conditions. This study is one of very few
      randomized trials on case management in a European setting. It examined the
      impact of case management on substance abuse and use of service after discharge
      from court-ordered institutional care. METHODS: Court-ordered patients with
      substance abuse ( n = 36) were randomly assigned to either strengths based case
      management or treatment-as-usual during 6 months in aftercare. Data was collected
      at intake, at conclusion of intervention and at 6 month's follow-up with a follow
      up rate of 94%. RESULTS: Case management interventions were well received by the
      patients with no drop-out during intervention. Patients with the support of a
      case manager seemed to sustain abstinence in a higher degree compared with
      treatment-as-usual but no differences were detected in regard to use of care. A
      subgroup analysis showed that patients with a continuous drug abuse did have
      access to care from both social welfare and hospital care systems. CONCLUSIONS:
      Case management may be useful in order to retain abstinence in aftercare
      following court-ordered treatment. The social welfare and hospital care systems
      seem to provide care irrespective of case manager intervention. The study design,
      interventions and assessments instruments were well received by patients but
      needs to be replicated with a larger population. CLINICAL IMPLICATIONS: The 100%
      retention in the case management support group indicates that patients were
      satisfied with this type of intervention and the methodology seems to be useful
      in order to retain abstinence.

PMID- 22853709
TI  - An antilock molecular braking system.
AB  - A light-driven molecular brake displaying an antilock function is constructed by
      introducing a nonradiative photoinduced electron transfer (PET) decay channel to
      compete with the trans (brake-off) -> cis (brake-on) photoisomerization. A fast
      release of the brake can be achieved by deactivating the PET process through
      addition of protons. The cycle of irradiation-protonation-irradiation
      deprotonation conducts the brake function and mimics the antilock braking system
      (ABS) of vehicles.

PMID- 22853708
TI  - Automated synthesis of a library of triazolated 1,2,5-thiadiazepane 1,1-dioxides
      via a double aza-Michael strategy.
AB  - The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1
      dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel
      synthesis platform, culminating in the successful preparation of 94 out of 96
      possible products. The key step, a one-pot, sequential elimination, double-aza
      Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated
      and utilized in the production of two sets of triazolated sultam products.

PMID- 22853710
TI  - Neuron-specific non-classical release of prothymosin alpha: a novel
      neuroprotective damage-associated molecular patterns.
AB  - Prothymosin alpha (ProTalpha), a nuclear protein devoid of signal sequence, has
      been shown to possess a number of cellular functions including cell survival.
      Most recently, we demonstrated that ProTalpha is localized in the nuclei of
      neurons, while it is found in both nuclei and cytoplasm in the astrocytes and
      microglia of adult brain. However, the cell type-specific non-classical release
      of ProTalpha under cerebral ischemia is yet unknown. In this study, we report
      that ProTalpha is non-classically released along with S100A13 from neurons in the
      hippocampus, striatum and somatosensory cortex at 3 h after cerebral ischemia,
      but amlexanox (an anti-allergic compound) reversibly blocks this neuronal
      ProTalpha release. We found that none of ProTalpha is released from astrocytes
      and microglia under ischemic stress. Indeed, ProTalpha intensity is increased
      gradually in astrocytes and microglia through 24 h after the cerebral ischemia.
      Interestingly, Z-Val-Ala-Asp fluoromethyl ketone, a caspase 3 inhibitor, pre
      treatment induces ProTalpha release from astrocytes in the ischemic brain, but
      this release is reversibly blocked by amlexanox. However, Z-Val-Ala-Asp
      fluoromethyl ketone as well as amlexanox has no effect on ProTalpha distribution
      in microglia upon cerebral ischemia. Taken together, these results suggest that
      only neurons have machineries to release ProTalpha upon cerebral ischemic stress
      in vivo.

PMID- 22853711
TI  - Diabetes self-risk assessment questionnaires coupled with a multimedia health
      promotion campaign are cheap and effective tools to increase public awareness of
      diabetes in a large Chinese population.
AB  - AIMS: To evaluate costs and effectiveness of implementing a diabetes self-risk
      assessment (Diabetes Risk Score) questionnaire coupled with a multimedia health
      promotion campaign on changes in diabetes awareness in a large diabetes
      prevention programme. METHODS: Between 2007 and 2010, a multimedia health
      promotion campaign was conducted targeting the 1.94 million population of
      Qingdao, China, using newspapers, radio programmes, distribution of free booklets
      and Diabetes Risk Score flyers. Diabetes awareness questionnaires filled out by
      people first interviewed in 2006 (survey A), before the initiation of the
      campaign, were compared with those first interviewed between 2007 and 2010 during
      the campaign period (survey B). The rates of diabetes awareness in both surveys
      were studied amongst adults aged 35-74 years without a prior history of diabetes,
      but with a Diabetes Risk Score of >= 14. RESULTS: In survey B, 85, 82 and 76% of
      the urban participants correctly recognized obesity, family history of diabetes
      and physical inactivity, respectively, as important risk factors for diabetes;
      while the awareness rates were 43, 46 and 25%, respectively, in survey A (P <
      0.001). The corresponding figures among rural participants were 65, 63 and 53% in
      survey B and 29, 22 and 11% in survey A (P < 0.001). To cover 1000 individuals,
      the programme spent ?5.4 on the use of the Diabetes Risk Score flyer, ?31.3 on
      the education booklet, ?7.7 on the newspaper campaign and ?37.5 on radio
      programmes. CONCLUSIONS: The combination of a Diabetes Risk Score questionnaire
      with a multimedia health promotion campaign is a cheap and effective health
      promotion tool to raise public awareness of diabetes.

PMID- 22853712
TI  - Cognitive rehabilitation in multiple sclerosis.
AB  - Cognitive impairments are frequent in multiple sclerosis (MS). However, most
      studies about efficacy of cognitive rehabilitation interventions have been
      criticized in terms of methods and/or design. The aim of this study is to
      evaluate the efficacy of cognitive rehabilitation in MS patients with a cognitive
      intervention (ProCogSEP* program), compared to a control intervention (discussion
      program). Twenty MS patients have completed this simple blind study: 10 patients
      followed 13 sessions (2 hours) of the ProCog-SEP(1) program. Ten other patients
      followed 13 sessions (2 hours) of a discussion program (Control Group). All
      patients underwent neuropsychological assessment, before and after their program,
      in order to evaluate cognitive functions. Two neuropsychologists respectively
      assessed the patients and conducted the group sessions. Compared to its own
      baseline, ProCog-SEP Group show improvements in verbal memory [free recall (p =
      .02), learning (p = .002)], in visual memory [free (p = .05) and delayed recall
      (p = .007)], in working-memory (p = .03), in verbal fluency (p = .05) and in
      language (p = .01). Inter group analysis show a benefit of cognitive program
      mainly in verbal and visual memory, and in verbal fluencies. These results
      support the interest of a cognitive therapeutic management of MS patients.

PMID- 22853713
TI  - Study of E/Z isomerization in a series of novel non-ligand binding pocket
      androgen receptor antagonists.
AB  - We report the conformational analysis of a series of 3-hydroxy-N'-((naphthalen-2
      yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently
      been reported as androgen receptor (AR)-coactivator disruptors for potential
      application in prostate cancer therapy. Definition of the E/Z isomerism around
      the imine linker group (hydrazide) is significant from a mechanistic point of
      view. A detailed study using theoretical calculations coupled with experimental
      techniques has allowed us determine an initial preference for the E isomer. The
      biological activity of newly synthesized compounds at the androgen receptor,
      along with a series of structural analogs, was determined and provides the basis
      for preliminary qualitative structure-activity relationship analysis.

PMID- 22853714
TI  - The effects of MicroRNA transfections on global patterns of gene expression in
      ovarian cancer cells are functionally coordinated.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that have been linked to
      a number of diseases including cancer. The potential application of miRNAs in the
      diagnostics and therapeutics of ovarian and other cancers is an area of intense
      interest. A current challenge is the inability to accurately predict the
      functional consequences of exogenous modulations in the levels of potentially
      therapeutic miRNAs. METHODS: In an initial effort to systematically address this
      issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR
      128). We monitored the consequent changes in global patterns of gene expression
      by microarray and quantitative (real-time) polymerase chain reaction. Network
      analysis of the expression data was used to predict the consequence of each
      transfection on cellular function and these predictions were experimentally
      tested. RESULTS: While ~20% of the changes in expression patterns of hundreds to
      thousands of genes could be attributed to direct miRNA-mRNA interactions, the
      majority of the changes are indirect, involving the downstream consequences of
      miRNA-mediated changes in regulatory gene expression. The changes in gene
      expression induced by individual miRNAs are functionally coordinated but distinct
      between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces
      changes in cell adhesion and other developmental networks previously associated
      with epithelial-mesenchymal transitions (EMT) and other processes linked with
      metastasis. In contrast, miR-128 transfection induces changes in cell cycle
      control and other processes commonly linked with cellular replication.
      CONCLUSIONS: The functionally coordinated patterns of gene expression displayed
      by different families of miRNAs have the potential to provide clinicians with a
      strategy to treat cancers from a systems rather than a single gene perspective.

PMID- 22853715
TI  - Getting back to work after injury: the UK Burden of Injury multicentre
      longitudinal study.
AB  - BACKGROUND: Injuries to working age adults are common and place a considerable
      burden on health services accounting for more than 10% of GP sick notes and 14%
      of those claiming benefits because they are unable to work in the UK. General
      practitioners (GPs) currently assess fitness to work and provide care and
      referral to other services to facilitate return to work (RTW). Recent UK
      recommendations suggest replacing GP sickness certification with independent
      assessments of fitness to work after four weeks sick leave. The impact of a wide
      range of injuries on RTW and subsequent need for independent fitness to work
      assessments has not been well studied in the UK. The aim of this study was to
      quantify RTW and factors predicting RTW following a wide range of injuries.
      METHODS: We used a multicentre longitudinal study, set in four acute NHS Trusts
      in the UK which recruited emergency department (ED) attenders and hospital
      admissions for injury and included those aged 16-65years that were employed or
      self-employed before the injury. Participants were followed up by postal
      questionnaire at 1, 4 and 12 months post injury to measure health status (EQ-5D),
      recovery, use of health and social services, time off work in the preceding month
      and work problems amongst those who had RTW. Multivariable Poisson regression
      with a robust variance estimator was used to estimate relative risks for factors
      associated with RTW. RESULTS: One month after injury 35% of ED attenders had
      fully RTW. The self employed were more likely (RR 1.70, 95% CI 1.17 to 2.47
      compared with employed) and the moderate/severely injured less likely to RTW (RR
      0.48, 95% CI 0.32 to 0.72 compared with minor injuries). At four months, 83% of
      ED attenders had RTW and self employment and injury severity remained significant
      predictors of RTW (self employment RR 1.15, 95% CI 1.03 to 1.30; moderate/severe
      injury RR 0.79, 95% CI 0.68 to 0.92). At four months 57% of hospital admissions
      had RTW. Men were more likely than women to RTW (RR 1.94, 95% CI 1.34 to 2.82),
      whilst those injured at work (RR 0.49, 95% CI 0.27 to 0.87 compared with at home)
      and those living in deprived areas (most deprived tertile RR 0.59, 95% CI 0.40 to
      0.85 and middle tertile RR 0.61, 95% CI 0.40 to 0.93) were less likely to RTW.
      Health status was significantly poorer at one and four months after injury than
      before the injury and was significantly poorer amongst those that had not RTW
      compared to those that had. Problems with pain control, undertaking usual
      activities, mobility and anxiety and depression were common and persisted in a
      considerable proportion of participants up to four months post injury.
      CONCLUSIONS: Injuries have a large impact on time off work, including amongst
      those whose injuries did not warrant hospital admission. The majority of injured
      people would require an in-depth fitness for work assessment if recent UK
      recommendations are implemented. Many people will have on-going pain, mobility
      problems, anxiety and depression at the point of assessment and it is important
      that patients are encouraged to use primary care services to address these
      problems. A range of factors may be useful for identifying those at risk of a
      slower recovery and a delayed RTW so that appropriate interventions can be
      provided to this group.

PMID- 22853716
TI  - Left atrial volume index as a marker of left ventricular diastolic dysfunction in
      asymptomatic Tanzanian diabetic patients.
AB  - AIM: To determine the prevalence of left atrial (LA) enlargement and its relation
      to left ventricular (LV) diastolic dysfunction among asymptomatic diabetic
      outpatients attending Muhimbili National Hospital in Dar es Salaam, Tanzania.
      METHODS: Echocardiography was performed in 122 type 2 and 58 type 1 diabetic
      patients. Diastolic dysfunction was defined as peak transmitral blood velocity to
      medial mitral annulus velocity (E/E') ratio >= 15. LA volume indexed to body
      surface area (LAVI) was considered enlarged if >= 29 ml/m(2). RESULTS: Enlarged
      LAVI and LV diastolic dysfunction were more common in type 2 than in type 1
      diabetic patients (44.3 vs 25.9% and 20.5 vs 3.5%, respectively, both p < 0.05).
      In multivariate linear regression analysis, larger LAVI was associated with LV
      diastolic dysfunction independent of significant associations with LV mass index
      and presence of mitral regurgitation in type 2 diabetic patients, while LV mass
      index, lower ejection fraction and longer duration of diabetes were the main
      covariates of larger LAVI in type 1 diabetic patients (all p < 0.05). CONCLUSION:
      Enlarged LA is common among asymptomatic Tanzanian diabetic patients, and
      particularly associated with LV diastolic dysfunction in type 2, and with
      cardiomyopathy and lower systolic function in type 1 diabetic patients.

PMID- 22853717
TI  - Pump-probe scheme to study the autoionization decay of optically-forbidden H2
      doubly excited states.
AB  - A pump-probe scheme is proposed to investigate the autoionization dynamics of the
      optically forbidden Q(1)(1)Sigma(g)(+) doubly excited states of the H(2)
      molecule. The scheme consists of a pump that contains an attosecond pulse train
      (APT) and an infrared (IR) pulse, which is phase-locked with the APT, and an IR
      probe identical to the former IR pulse. The dynamical information is obtained by
      analyzing the electron kinetic energy spectra (EKE) and proton kinetic energy
      spectra (PKE) as a function of the time delay between the pump and the probe. The
      essential requirement for an efficient population of the Q(1)(1)Sigma(g)(+)
      states is that they are resonantly coupled to both the dipole-allowed
      Q(1)(1)Sigma(u)(+) doubly excited states and the ground state of H(2) by the
      combined effect of the APT + IR fields.

PMID- 22853718
TI  - Technology to inform insulin dose adjustments: its time is near.

PMID- 22853719
TI  - Screening for and prevention of diabetes in India: need for simple and innovative
      strategies.

PMID- 22853720
TI  - Outpatient assessment of determinants of glucose excursions in adolescents with
      type 1 diabetes: proof of concept.
AB  - Abstract   Objective: Controlled inpatient studies on the effects of food,
      physical activity (PA), and insulin dosing on glucose excursions exist, but such
      outpatient data are limited. We report here outpatient data on glucose excursions
      and its key determinants over 5 days in 30 adolescents with type 1 diabetes (T1D)
      as a proof-of-principle pilot study. SUBJECTS AND METHODS: Subjects (20 on
      insulin pumps, 10 receiving multiple daily injections; 15+/-2 years old; diabetes
      duration, 8+/-4 years; hemoglobin A1c, 8.1+/-1.0%) wore a continuous glucose
      monitor (CGM) and an accelerometer for 5 days. Subjects continued their existing
      insulin regimens, and time-stamped insulin dosing data were obtained from insulin
      pump downloads or insulin pen digital logs. Time-stamped cell phone photographs
      of food pre- and post-consumption and food logs were used to augment 24-h dietary
      recalls for Days 1 and 3. These variables were incorporated into regression
      models to predict glucose excursions at 1-4 h post-breakfast. RESULTS: CGM data
      on both Days 1 and 3 were obtained in 57 of the possible 60 subject-days with an
      average of 125 daily CGM readings (out of a possible 144). PA and dietary recall
      data were obtained in 100% and 93% of subjects on Day 1 and 90% and 100% of
      subjects on Day 3, respectively. All of these variables influenced glucose
      excursions at 1-4 h after waking, and 56 of the 60 subject-days contributed to
      the modeling analysis. CONCLUSIONS: Outpatient high-resolution time-stamped data
      on the main inputs of glucose variability in adolescents with T1D are feasible
      and can be modeled. Future applications include using these data for in silico
      modeling and for monitoring outpatient iterations of closed-loop studies, as well
      as to improve clinical advice regarding insulin dosing to match diet and PA
      behaviors.

PMID- 22853721
TI  - A comprehensive evaluation of the performance of the test strip technology for
      OneTouch Verio glucose meter systems.
AB  - BACKGROUND: OneTouch(r) VerioTM test strips (LifeScan Inc., Milpitas, CA) are
      designed to minimize error when used in blood glucose monitoring systems. These
      strips have a specialized architecture and incorporate a sophisticated waveform
      and proprietary algorithm. MATERIALS AND METHODS: Performance of OneTouch Verio
      test strips was assessed in the laboratory in the presence of a wide range of
      patient, environmental, and pharmacologic factors. A clinical evaluation was
      conducted in which 296 patients and healthcare professionals (HCPs) performed
      glucose testing using OneTouch Verio test strips and OneTouch VerioIQ meters.
      RESULTS: In the laboratory study, OneTouch Verio test strip results achieved a
      high level of performance over a wide range of hematocrit (19-61%), temperature
      (5-45( degrees )C), humidity (10-90% relative humidity), and altitude (0-3,048 m)
      conditions. Performance was not affected by 22 of 23 chemical compounds. In the
      clinical study, 100% (31/31) of lay-user test results were within +/-10 mg/dL of
      reference values for blood glucose <75 mg/dL. At blood glucose >=75 mg/dL, 99.2%
      (243/245) were within +/-15% of reference values. A feature of the VerioIQ meter,
      PatternAlert(TM) Technology, was correctly used and positively evaluated by >98%
      of lay users. CONCLUSIONS: OneTouch Verio test strips are accurate and precise
      over a wide range of patient, environmental, and pharmacologic conditions. In
      addition, lay-users were able to successfully use the OneTouch VerioIQ
      PatternAlert Technology without HCP training.

PMID- 22853722
TI  - The accuracy and efficacy of real-time continuous glucose monitoring sensor in
      Chinese diabetes patients: a multicenter study.
AB  - BACKGROUND: The purpose of this multicenter study was to investigate the accuracy
      of a real-time continuous glucose monitoring sensor in Chinese diabetes patients.
      SUBJECTS AND METHODS: In total, 48 patients with type 1 or 2 diabetes from three
      centers in China were included in the study. The MiniMed Paradigm((r)) 722
      insulin pump (Medtronic, Northridge, CA) was used to monitor the real-time
      continuous changes of blood glucose levels for three successive days. Venous
      blood of the subjects was randomly collected every 15 min for seven consecutive
      hours on the day when the subjects were wearing the sensor. Reference values were
      provided by the YSI((r)) 2300 STAT PLUSTM glucose and lactate analyzer (YSI Life
      Sciences, Yellow Springs, OH). RESULTS: In total, 1,317 paired YSI-sensor values
      were collected from the 48 patients. Of the sensor readings, 88.3% (95%
      confidence interval, 0.84-0.92) were within+/-20% of the YSI values, and 95.7%
      were within+/-30% of the YSI values. Clarke and consensus error grid analyses
      showed that the ratios of the YSI-sensor values in Zone A to the values in Zone B
      were 99.1% and 99.9%, respectively. Continuous error grid analysis showed that
      the ratios of the YSI-sensor values in the region of accurate reading, benign
      errors, and erroneous reading were 96.4%, 1.8%, and 1.8%, respectively. The mean
      absolute relative difference (ARD) for all subjects was 10.4%, and the median ARD
      was 7.8%. Bland-Altman analysis detected a mean blood glucose level of 3.84
      mg/dL. Trend analysis revealed that 86.1% of the difference of the rates of
      change between the YSI values and the sensor readings occurred within the range
      of 1 mg/dL/min. CONCLUSIONS: The Paradigm insulin pump has high accuracy in both
      monitoring the real-time continuous changes and predicting the trend of changes
      in blood glucose level. However, actual clinical manifestations should be taken
      into account for diagnosis of hypoglycemia.

PMID- 22853723
TI  - Feasibility study of automated overnight closed-loop glucose control under MD
      logic artificial pancreas in patients with type 1 diabetes: the DREAM Project.
AB  - BACKGROUND: Artificial pancreas systems may offer a potential major impact on the
      normalization of metabolic control and preventing hypoglycemic events. This study
      aims to establish near-normal overnight glucose control and reduce the risk of
      nocturnal hypoglycemia using the MD-Logic Artificial Pancreas (MDLAP), an
      algorithm that was developed by our research group. This inpatient feasibility
      study is the first step towards implementing an overnight closed-loop MDLAP
      system at the patient's home. SUBJECTS AND METHODS: Seven patients with type 1
      diabetes (three adolescents and four adults; mean+/-SD age, 20.6+/-4.7 years;
      duration of diabetes, 9.6+/-2.6 years; body mass index, 24.3+/-3.9 kg/m(2); and
      glycated hemoglobin, 7.8+/-0.8%) participated in a total of 14 closed-loop
      overnight sessions. Each participant underwent two closed-loop inpatient sessions
      starting at dinner alone and at dinner following exercise. The closed-loop
      inpatient sessions were compared with data derived from nights spent at home with
      an open-loop system in a similar scenario to the study protocol. RESULTS: The
      mean percentage of time spent in the near normal glucose range of 63-140 mg/dL
      was 83+/-16%, and the median (interquartile range) was 85% (78-92%) for the
      overnight closed-loop sessions compared with 34+/-31% and 27% (6-57%) in the
      homecare open-loop setting, respectively. During the overnight closed-loop
      sessions at dinner alone 92+/-9% of the sensor values ranged within target range,
      compared with 73+/-19% for the sessions following exercise (P=0.03). No
      hypoglycemic (<63 mg/dL) events occurred during the closed-loop sessions.
      CONCLUSION: Closed-loop insulin delivery under MDLAP is a feasible and safe
      solution to control overnight glycemia.

PMID- 22853724
TI  - Usefulness of acarbose and dietary modifications to limit glycemic variability
      following Roux-en-Y gastric bypass as assessed by continuous glucose monitoring.
AB  - BACKGROUND: About 70% of the patients operated on for a gastric bypass (Roux-en-Y
      gastric bypass [RYGB]) suffer from dumping syndrome. In these patients, previous
      studies have demonstrated a high glycemic variability with hypoglycemia and with
      altered continuous glucose monitoring (CGM) profiles. The aim of this study was
      to evaluate the effect of treatment with dietary counseling plus acarbose
      administration on the symptoms and on the characteristics of the CGM profile.
      SUBJECTS AND METHODS: Eight consecutive patients with dumping syndrome were given
      dietary counseling for 6 weeks and also treated with acarbose (50-100 mg three
      times a day). Their symptoms and the features of the CGM were compared before and
      after treatment. RESULTS: The symptoms disappeared in seven patients. There was a
      significant increase in the time to the interstitial glucose (IG) peak and a
      reduction in the rate of the IG increase after a meal and in the rate of the IG
      decrease following the peak. The time below 60 mg/dL was significantly decreased,
      and the minimal IG value was significantly increased. The maximum and mean IG
      levels and the time above 140 mg/dL were decreased, but not significantly. Six
      patients spent more than 1% of the time with IG values below 60 mg/dL before
      treatment, but after treatment this was reduced to one patient. Before treatment
      only one patient had an IG level neither below 60 or above 140 mg/dL, and after
      treatment four patients were in this category. CONCLUSIONS: Dietary counseling
      and acarbose treatment eliminated the symptoms and improved the CGM profile of
      patients suffering from dumping syndrome after RYGB.

PMID- 22853726
TI  - Subclinical thyroid disease: time to enter the age of evidence-based medicine.

PMID- 22853727
TI  - Outcomes and prognostic factors of 251 patients with minimally invasive
      follicular thyroid carcinoma.
AB  - BACKGROUND: Radioiodine ablation after total thyroidectomy is the generally
      accepted treatment for patients with widely invasive follicular thyroid carcinoma
      (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is
      still a matter of controversy. The histological diagnosis of minimally invasive
      FTC is often made after lobectomy. The aim of this study was to determine the
      factors associated with the development of distant metastases in patients with
      minimally invasive FTC. METHODS: Between 1989 and 2006, 251 patients with
      minimally invasive FTC underwent initial surgery at our hospital. Their median
      follow-up period was 7.2 years. There were 194 women and 57 men. Their mean age
      at the time of surgery was 46 years. Distant metastases were diagnosed in 54
      patients (21.5%). In 22 of them distant metastases were diagnosed at the time of
      the initial surgery (M1), and in the other 32 they were diagnosed during the
      follow-up period. Age at initial surgery, sex, primary tumor size, histological
      findings (differentiation, and extent of vascular and capsular invasion),
      completion total thyroidectomy, and distant metastases at initial surgery were
      assessed as prognostic factors for distant-metastases-free survival (DMFS) and
      cause-specific survival (CSS). The Kaplan-Meier method and log-rank test were
      used to analyze time-dependent variables. The Cox proportional hazard model was
      used to perform the multivariate analysis. RESULTS: Univariate analysis showed
      that age (45 years or older) and primary tumor size (4 cm or more) were
      significant prognostic factors related to postoperative distant metastases in the
      group of 229 patients without distant metastases at time of the initial surgery.
      The cumulative survival rate was significantly poorer in M1 patients, patients
      aged 45 years or older, and patients whose primary tumor size was 4 cm or more.
      Multivariate analysis showed that age was a significant prognostic factor both
      for DMFS and CSS. CONCLUSIONS: Age was the most powerful prognostic factor for
      patients with minimally invasive follicular thyroid cancer. The prognoses of
      patients younger than 45 years old were excellent and distant metastases rarely
      occurred. Routine completion total thyroidectomy and radioiodine ablation is
      thought unnecessary for these patients.

PMID- 22853725
TI  - Examining the relationship between diet-induced acidosis and cancer.
AB  - Increased cancer risk is associated with select dietary factors. Dietary
      lifestyles can alter systemic acid-base balance over time. Acidogenic diets,
      which are typically high in animal protein and salt and low in fruits and
      vegetables, can lead to a sub-clinical or low-grade state of metabolic acidosis.
      The relationship between diet and cancer risk prompts questions about the role of
      acidosis in the initiation and progression of cancer. Cancer is triggered by
      genetic and epigenetic perturbations in the normal cell, but it has become clear
      that microenvironmental and systemic factors exert modifying effects on cancer
      cell development. While there are no studies showing a direct link between diet
      induced acidosis and cancer, acid-base disequilibrium has been shown to modulate
      molecular activity including adrenal glucocorticoid, insulin growth factor (IGF
      1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and
      osteoclast activation, which may serve as intermediary or downstream effectors of
      carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence
      molecular activities at the cellular level that promote carcinogenesis or tumor
      progression. This review defines the relationship between dietary lifestyle and
      acid-base balance and discusses the potential consequences of diet-induced
      acidosis and cancer occurrence or progression.

PMID- 22853728
TI  - Postradioiodine treatment whole-body scan in the era of 18-fluorodeoxyglucose
      positron emission tomography for differentiated thyroid carcinoma with elevated
      serum thyroglobulin levels.
AB  - BACKGROUND: Patients with differentiated thyroid cancer (DTC) who have a
      suspicious recurrent or persistent disease based on an elevated serum
      thyroglobulin (Tg) or Tg antibodies (TgAb) are usually referred for empiric
      radioiodine ((131)I) administration to localize and treat the disease. The aim of
      this retrospective monocentric study was to assess the sensitivity of postempiric
      (131)I whole-body scan (WBS) compared to 18-fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography (PET/CT) in such patients who had an
      initial normal postablation WBS. METHODS: Among 47 consecutive patients with DTC
      who had a normal postablation WBS and were referred for empiric (131)I
      administration, 34 patients (12M, 22F; mean age 53 years) underwent FDG PET/CT
      and form the basis of this report: 23 patients had persistently elevated serum Tg
      levels, 10 had elevated Tg levels observed during follow-up after they initially
      became under 1 ng/mL, and 1 had appearance of TgAb during follow-up. Postempiric
      (131)I WBS and FDG PET/CT were analyzed by independent readers. RESULTS: A total
      of 75 lesions were found in 23 patients, distributed in 36 organs. Lesions were
      located in the neck (30), lungs (28), mediastinum (11), and bones (6). The
      sensitivities for the detection of individual lesions and for the diagnosis of
      metastatic organs were 88% and 97% for PET/CT and 16% and 22% for WBS,
      respectively (p<0.01). PET/CT was abnormal in 22 patients, among which 5 also had
      an abnormal postempiric (131)I WBS. There was only one patient with an abnormal
      postempiric (131)I WBS and a normal FDG PET/CT. This patient underwent two
      further (131)I administrations, with the last WBS being normal and the last
      stimulated Tg level being undetectable. Other patients were either treated with
      surgery, or classified as radioactive iodine refractory and treated with
      levothyroxine suppressive therapy or tyrosine kinase inhibitors. CONCLUSION: In
      patients with suspicious recurrence based on the Tg level after a normal
      postablation WBS, FDG PET/CT is the preferred scintigraphic method to localize
      disease rather than postempiric (131)I WBS. Empiric (131)I administration may be
      used only in patients who do not have a significant FDG uptake.

PMID- 22853729
TI  - Propylthiouracil increases sodium/iodide symporter gene expression and iodide
      uptake in rat thyroid cells in the absence of TSH.
AB  - BACKGROUND: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are
      widely used to treat Graves' disease. Although both exert an antithyroid effect
      primarily by blocking thyroid peroxidase activity, their molecular structure and
      other actions are different. We hypothesized that PTU and MMI may have
      differential effects on thyroid-specific gene expression and function. METHODS:
      The effects of PTU and MMI on thyroid-specific gene expression and function were
      examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase
      (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot,
      immunohistochemistry, and radioiodine uptake studies. RESULTS: DNA microarray
      analysis showed a marked increase in sodium/iodide symporter (NIS) gene
      expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time
      PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those
      elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'
      1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS
      protein levels, the size of the induced protein was smaller than that induced by
      TSH, and the protein localized predominantly in the cytoplasm rather than the
      plasma membrane. Accumulation of (125)I in FRTL-5 cells was increased by PTU
      stimulation, but this effect was weaker than that produced by TSH. CONCLUSIONS:
      We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5
      cells in the absence of TSH. Although PTU and MMI share similar antithyroid
      activity, their effects on other thyroid functions appear to be quite different,
      which could affect their therapeutic effectiveness.

PMID- 22853731
TI  - Determination of cutpoints for low and high number of symptoms in patients with
      advanced cancer.
AB  - While patients with advanced cancer experience a wide range of symptoms, no work
      has been done to determine an optimal cutpoint for a low versus a high number of
      symptoms. Analytic approaches that established clinically meaningful cutpoints
      for the severity of cancer pain and fatigue provided the foundation for this
      study. The purpose of this study was to determine the optimal cutpoint for low
      and high numbers of symptoms using a range of potential cutpoints and to
      determine if those cutpoints distinguished between the two symptom groups on
      demographic and clinical characteristics and depression, anxiety, and quality of
      life (QOL). Patients with advanced cancer (n=110) completed a symptom assessment
      scale, and measures of depression, anxiety, and QOL. Combinations of cutpoints
      were tested to yield one- and two-cutpoint solutions. Using analysis of variance
      for QOL scores, the F-ratio that indicated the highest between-group difference
      was determined to be the optimal cutpoint between low and high number of
      symptoms. A cutpoint of <= 12 symptoms (i.e., 0-12 is low, 13-32 is high) was the
      optimal cutpoint for total number of symptoms. Significant differences in
      depression, anxiety, and QOL scores validated this cutpoint. Psychological
      symptoms had higher occurrence rates in the high symptom group. Findings suggest
      that a threshold exists between a low and a high number of symptoms in patients
      with advanced cancer. Psychological symptoms were significantly different between
      patients in the low versus high symptom groups and may play an important role in
      QOL outcomes in patients with advanced cancer.

PMID- 22853734
TI  - Synthesis of CuTCNQ/Au microrods by galvanic replacement of semiconducting phase
      I CuTCNQ with KAuBr4 in aqueous medium.
AB  - The spontaneous reaction between microrods of an organic semiconductor molecule,
      copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) with [AuBr(4)](-) ions in an
      aqueous environment is reported. The reaction is found to be redox in nature
      which proceeds via a complex galvanic replacement mechanism, wherein the surface
      of the CuTCNQ microrods is replaced with metallic gold nanoparticles. Unlike
      previous reactions reported in acetonitrile, the galvanic replacement reaction in
      aqueous solution proceeds via an entirely different reaction mechanism, wherein a
      cyclical reaction mechanism involving continuous regeneration of CuTCNQ consumed
      during the galvanic replacement reaction occurs in parallel with the galvanic
      replacement reaction. This results in the driving force of the galvanic
      replacement reaction in aqueous medium being largely dependent on the
      availability of [AuBr(4)](-) ions during the reaction. Therefore, this study
      highlights the importance of the choice of an appropriate solvent during galvanic
      replacement reactions, which can significantly impact upon the reaction
      mechanism. The reaction progress with respect to different gold salt
      concentration was monitored using Fourier transform infrared (FT-IR), Raman, and
      X-ray photoelectron spectroscopy (XPS), as well as XRD and EDX analysis, and SEM
      imaging. The CuTCNQ/Au nanocomposites were also investigated for their potential
      photocatalytic properties, wherein the destruction of the organic dye, Congo red,
      in a simulated solar light environment was found to be largely dependent on the
      degree of gold nanoparticle surface coverage. The approach reported here opens up
      new possibilities of decorating metal-organic charge transfer complexes with a
      host of metals, leading to potentially novel applications in catalysis and
      sensing.

PMID- 22853732
TI  - Insights into deregulated TNF and IL-10 production in malaria: implications for
      understanding severe malarial anaemia.
AB  - BACKGROUND: Severe malarial anaemia (SMA) is a major life-threatening
      complication of paediatric malaria. Protracted production of pro-inflammatory
      cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought
      to play an important role in SMA, which is characterized by a high TNF/IL-10
      ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of
      SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is
      unknown. Monocytes and T cells are recognized as the main sources of TNF and IL
      10 in vivo, but little is known about the activation status of those cells in SMA
      patients. METHODS: The IL-10 and TNF production capacity and the activation
      phenotype of monocytes and T cells were compared in samples collected from 332
      Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n =
      144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of
      monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface
      expression by flow cytometry. The TNF and IL-10 production was assessed in a
      whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or
      phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell
      stimulant. The number of circulating pigmented monocytes was also determined.
      RESULTS: Monocytes and T cells from SMA and CM patients showed similar activation
      profiles with a comparable decreased HLA-DR expression on monocytes and increased
      frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10
      production was markedly decreased in SMA compared to CM (P = .003) and UM (P =
      .004). Although in SMA the IL-10 response to LPS-stimulation was larger in
      amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower
      (P = .013). Both the amplitude and levels of TNF produced in response to LPS
      stimulation were larger in SMA than CM (P = .019). In response to PHA
      stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P =
      .005) contrasting with TNF levels, which were higher (P = .001). CONCLUSIONS:
      These data reveal that SMA patients have the potential to mount efficient IL-10
      responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T
      cell programming/polarization pattern in response to infection.

PMID- 22853733
TI  - Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney
      with ischemic postconditioning application and trimetazidine treatment.
AB  - BACKGROUND: Endoplasmic reticulum (ER) and mitochondria have been implicated in
      the pathology of renal ischemia/reperfusion (I/R). In the present study, we
      investigated whether the use of ischemic postconditioning (IPostC) and
      trimetazidine (TMZ) separately or combined could reduce ER stress and
      mitochondria damage after renal ischemia. METHODS: Kidneys of Wistar rats were
      subjected to 60-min of warm ischemia followed by 120-min of reperfusion (I/R
      group, n = 6), or to 6 cycles of ischemia/reperfusion (10-s each cycle) just
      after 60-min of warm ischemia (IPostC group, n = 6), or to i.p. injection of TMZ
      (3 mg/kg) 30-min before ischemia (TMZ group, n = 6), or to the combination of
      both treatments (IPostC+TMZ group, n = 6). The results of these experimental
      groups were compared to those of a sham-operated group in which rat renal
      pedicles were only dissected. Sodium reabsorption rate, creatinine clearance
      lactate deshydrogenase (LDH) activity in plasma, and concentration of
      malonedialdehyde (MDA) in tissue were determined. In addition, Western blot
      analysis was performed to identify the amounts of cytochrome c, c-JunNH2-terminal
      kinase (JNK), voltage-dependent anion channel (VDAC), glycogen synthase kinase 3
      beta (GSK3-beta), and ER stress parameters. RESULTS: IPostC or/and TMZ
      significantly decreased cytolysis, oxidative stress and improved renal function
      in comparison to I/R group. IPostC but not TMZ significantly attenuated ER stress
      parameters versus I/R group. Indeed, it down-regulated the glucose-regulated
      protein 78 (GRP78), the activating transcription factor 4 (ATF4), the RNA
      activated protein kinase (PKR)-like ER kinas (PERK), the X box binding protein-1
      (XBP-1) and the caspase12 protein levels. TMZ treatment significantly augmented
      GSK3-beta phosphorylation and reduced levels of cytochrome c and VDAC
      phosphorylation in comparison to IPostC application. The combination of both
      treatments gave a synergetic effect. It significantly improved the survival rate,
      attenuated cytolysis, oxidative stress and improved renal function. CONCLUSION:
      This study revealed that IPostC protects kidney from I/R injury by suppressing ER
      stress while the beneficial effects of TMZ are mediated by mitochondria
      protection. The combination of both treatments ameliorated functional recovery.

PMID- 22853735
TI  - Combinational risk factors of metabolic syndrome identified by fuzzy neural
      network analysis of health-check data.
AB  - BACKGROUND: Lifestyle-related diseases represented by metabolic syndrome develop
      as results of complex interaction. By using health check-up data from two large
      studies collected during a long-term follow-up, we searched for risk factors
      associated with the development of metabolic syndrome. METHODS: In our original
      study, we selected 77 case subjects who developed metabolic syndrome during the
      follow-up and 152 healthy control subjects who were free of lifestyle-related
      risk components from among 1803 Japanese male employees. In a replication study,
      we selected 2196 case subjects and 2196 healthy control subjects from among 31343
      other Japanese male employees. By means of a bioinformatics approach using a
      fuzzy neural network (FNN), we searched any significant combinations that are
      associated with MetS. To ensure that the risk combination selected by FNN
      analysis was statistically reliable, we performed logistic regression analysis
      including adjustment. RESULTS: We selected a combination of an elevated level of
      gamma-glutamyltranspeptidase (gamma-GTP) and an elevated white blood cell (WBC)
      count as the most significant combination of risk factors for the development of
      metabolic syndrome. The FNN also identified the same tendency in a replication
      study. The clinical characteristics of gamma-GTP level and WBC count were
      statistically significant even after adjustment, confirming that the results
      obtained from the fuzzy neural network are reasonable. Correlation ratio showed
      that an elevated level of gamma-GTP is associated with habitual drinking of
      alcohol and a high WBC count is associated with habitual smoking. CONCLUSIONS:
      This result obtained by fuzzy neural network analysis of health check-up data
      from large long-term studies can be useful in providing a personalized novel
      diagnostic and therapeutic method involving the gamma-GTP level and the WBC
      count.

PMID- 22853737
TI  - Surface analysis of ionic liquids with and without lithium salt using X-ray
      photoelectron spectroscopy.
AB  - X-ray photoelectron spectroscopy (XPS) was applied to a neat ionic liquid 1-ethyl
      3-methylimidazolium bis(trifluoromethanesulfonyl)imide [EMI(+)][Tf(2)N(-)] and
      its lithium salt solution at room temperature to clarify the composition and
      structure of its near-surface region. Core level peaks were recorded for Li 1s, N
      1s, C 1s, F 1s, O 1s, S 2s, and S 2p. Valence band XPS spectra (0-40 eV binding
      energy) were also studied. The XPS spectra were analyzed using DV-Xalpha
      calculations. Results show that the planar type isomer of the EMI(+) cation is
      dominant at the near-surface region of EMI-Tf(2)N. Results of XPS measurements
      show a spectrum of Li 1s in Li/EMI-Tf(2)N. The proposed models for the preferred
      orientation of the ions exhibit good agreement with results obtained from the DV
      Xalpha calculations.

PMID- 22853736
TI  - Acute posthypoxic myoclonus after cardiopulmonary resuscitation.
AB  - BACKGROUND: Acute posthypoxic myoclonus (PHM) can occur in patients admitted
      after cardiopulmonary resuscitation (CPR) and is considered to have a poor
      prognosis. The origin can be cortical and/or subcortical and this might be an
      important determinant for treatment options and prognosis. The aim of the study
      was to investigate whether acute PHM originates from cortical or subcortical
      structures, using somatosensory evoked potential (SEP) and electroencephalogram
      (EEG). METHODS: Patients with acute PHM (focal myoclonus or status myoclonus)
      within 72 hours after CPR were retrospectively selected from a multicenter cohort
      study. All patients were treated with hypothermia. Criteria for cortical origin
      of the myoclonus were: giant SEP potentials; or epileptic activity, status
      epilepticus, or generalized periodic discharges on the EEG (no back-averaging was
      used). Good outcome was defined as good recovery or moderate disability after 6
      months. RESULTS: Acute PHM was reported in 79/391 patients (20%). SEPs were
      available in 51/79 patients and in 27 of them (53%) N20 potentials were present.
      Giant potentials were seen in 3 patients. EEGs were available in 36/79 patients
      with 23/36 (64%) patients fulfilling criteria for a cortical origin. Nine
      patients (12%) had a good outcome. A broad variety of drugs was used for
      treatment. CONCLUSIONS: The results of this study show that acute PHM originates
      from subcortical, as well as cortical structures. Outcome of patients admitted
      after CPR who develop acute PHM in this cohort was better than previously
      reported in literature. The broad variety of drugs used for treatment shows the
      existing uncertainty about optimal treatment.

PMID- 22853738
TI  - Oscillatory entrainment of subthalamic nucleus neurons and behavioural
      consequences in rodents and primates.
AB  - We investigated the functional role of oscillatory activity in the local field
      potential (LFP) of the subthalamic nucleus (STN) in the pathophysiology of
      Parkinson's disease (PD). It has been postulated that beta (15-30 Hz) oscillatory
      activity in the basal ganglia induces PD motor symptoms. To assess this
      hypothesis, an LFP showing significant power in the beta frequency range (23 Hz)
      was used as a stimulus both in vitro and in vivo. We first demonstrated in rat
      brain slices that STN neuronal activity was driven by the LFP stimulation. We
      then applied beta stimulation to the STN of 16 rats and two monkeys while
      quantifying motor behaviour. Although stimulation-induced behavioural effects
      were observed, stimulation of the STN at 23 Hz induced no significant decrease in
      motor performance in either rodents or primates. This study is the first to show
      LFP-induced behaviour in both rats and primates, and highlights the complex
      relationship between beta power and parkinsonian symptoms.

PMID- 22853739
TI  - Therapeutic concentrations of antibiotics inhibit Shiga toxin release from
      enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak.
AB  - BACKGROUND: The shiga toxin-producing E. coli (STEC) O104:H4 caused a major
      outbreak in Germany in spring 2011. STEC are usually susceptible to common
      antibiotics. However, antibiotic treatment of STEC-infected patients is not
      recommended because STEC may enhance production and release of shiga toxins (STX)
      in response to antibiotics, which eventually enhances the frequency and severity
      of clinical symptoms, including haemolytic uraemic syndrome (HUS) and fatalities.
      RESULTS: We characterized the response to antibiotics of STEC O104:H4 isolates
      from two HUS patients during the German STEC outbreak in spring 2011 in
      comparison to the common STEC O157:H7. Liquid cultures of STEC O157:H7 and
      O104:H4 were incubated with graded dilutions of the antibiotics ciprofloxacin,
      meropenem, fosfomycin, gentamicin, rifampicin, and chloramphenicol. At defined
      times of antibiotic treatment, transcriptional activation of the STX2 gene,
      contents of STX and STX-activity in the culture supernatants were quantified.
      Unlike the common serotype O157:H7, STEC O104:H4 does not release STX in response
      to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and
      chloramphenicol. CONCLUSIONS: In future outbreaks, the response of the respective
      epidemiologic STEC strain to antibiotics should be rapidly characterized in order
      to identify antibiotics that do not enhance the release of STX. This will
      eventually allow clinical studies tackling the question whether antibiotic
      treatment impacts on the eradication of STEC, clinical course of disease, and
      frequency of carriers.

PMID- 22853741
TI  - Reevaluation of arrhythmias and alterations of the autonomic nervous activity
      induced by T-2 toxin through telemetric measurements in unrestrained rats.
AB  - This study was conducted to clarify and reevaluate the cardiac and autonomic
      nervous effects of T-2 toxin, which had been previously examined by several acute
      experiments, in unrestrained and conscious rats implanted with telemetric
      transmitters. Two groups of rats were given two subcutaneous injections of 0.1
      and 0.5 mg/kg of T-2 toxin with an interval of 3 days. Two other groups of rat
      were pre-implanted with osmotic minipumps by which atropine (20 mg/kg/day) or
      propranolol (100 mg/kg/day) was continuously administered preceding subcutaneous
      injection of T-2 toxin (0.5 mg/kg). The present study demonstrated that T-2 toxin
      caused marked arrhythmias, such as second-degree atrioventricular (AV) block,
      sinus bradycardia, supraventricular extrasystole, and ventricular extrasystole,
      which were accompanied by a significant increase in heart rate and a significant
      decrease in total power and low- and high-frequency power of heart rate
      variability, during 3 days of observation after the toxin administration.
      However, the occurrence of arrhythmia with conduction disturbance such as second
      degree atrioventricular blocks was markedly diminished by pretreatment with
      atropine, while the occurrence of ventricular extrasystole was augmented by
      atropine. The present study with the telemetric measurement elucidated and
      confirmed that T-2 toxin produced significant cardiac dysfunctions involving
      disturbance of the conduction pathway influenced by the autonomic nervous
      activity and also possible direct effects on cardiac myocytes.

PMID- 22853740
TI  - Medical device assessment: scientific evidence examined by the French national
      agency for health - a descriptive study.
AB  - BACKGROUND: Scientific evidence supports decision-making on the use of
      implantable medical devices (IMDs) in clinical practice, but IMDs are thought to
      be far less investigated than drugs. In the USA, studies have shown that approval
      process of high-risk medical devices was often based on insufficiently robust
      studies, suggesting that evidence prior to marketing may not be adequate. This
      study aimed to ascertain level of evidence available for IMDs access to
      reimbursement in France. METHODS: The objective was to examine the scientific
      evidence used for IMDs assessment by the French National Authority for Health. We
      collected all public documents summarising supportive clinical data and opinions
      concerning IMDs issued in 2008. An opinion qualifies the expected benefit (EB) of
      the IMD assessed as sufficient or insufficient, and if sufficient, the level of
      improvement of the expected benefit (IEB) on a scale from major (level I) to no
      improvement (level V). For each opinion, the study with the highest level of
      evidence of efficacy data, and its design were collected, or, where no studies
      were available, any other data sources used to establish the opinion. RESULTS:
      One hundred and two opinions were analysed, with 72 reporting at least one study
      used for assessment (70.6%). When considering the study with the highest level of
      evidence: 34 were clinical non-comparative studies (47.2%); 29 were clinical
      comparative studies of which 25 randomised controlled trials (40.3%); 5 were meta
      analyses of randomised controlled trials (6.9%); and 4 were systematic literature
      reviews (5.6%). The opinions were significantly different according to the study
      design (p < 0.001). The most frequent design for insufficient EB, IEB level V and
      IEB level IV was a non-comparative study (10/19, 52.6%; 15/24, 62.5%; and 8/15,
      53.3%; respectively). For the 30 opinions with no supporting clinical study, 16
      (53.3%) were based on an expert-based process, 9 (30.0%) were based on the
      conclusions of a previous opinion (all concluding IEB level V), and 5 (16.7%)
      reported no data (concluding insufficient EB for 4 and IEB level V for 1).
      CONCLUSIONS: This study confirmed that level of evidence of clinical evaluation
      of IMDs is low and needs to be improved.

PMID- 22853742
TI  - An international survey of daily disposable contact lens prescribing.
AB  - PURPOSE: The aim was to determine the extent of daily disposable contact lens
      prescribing worldwide and to characterise the associated demographics and fitting
      patterns. METHODS: Up to 1,000 survey forms were sent to contact lens fitters in
      up to 40 countries between January and March every year for five consecutive
      years (2007 to 2011). Practitioners were asked to record data relating to the
      first 10 contact lens fits or refits performed after receiving the survey form.
      Survey data collected since 1996 were also analysed for seven nations to assess
      daily disposable lens fitting trends since that time. RESULTS: Data were
      collected in relation to 97,289 soft lens fits, of which 23,445 (24.1 per cent)
      were with daily disposable lenses and 73,170 (75.9 per cent) were with reusable
      lenses. Daily disposable lens prescribing ranged from 0.6 per cent of all soft
      lenses in Nepal to 66.2 per cent in Qatar. Compared with reusable lens fittings,
      daily disposable lens fittings can be characterised as follows: older age (30.0
      +/- 12.5 versus 29.3 +/- 12.3 years for reusable lenses); males are over
      represented; a greater proportion of new fits versus refits; 85.9 per cent
      hydrogel; lower proportion of toric and presbyopia designs and a higher
      proportion of part-time wear. There has been a continuous increase in daily
      disposable lens prescribing between 1996 and 2011. The proportion of daily
      disposable lens fits (as a function of all soft lens fits) is positively related
      to the gross domestic product at purchasing power parity per capita (r(2) = 0.55,
      F = 46.8, p < 0.0001). CONCLUSIONS: The greater convenience and other benefits of
      daily disposable lenses have resulted in this modality capturing significant
      market share. The contact lens field appears to be heading toward a true single
      use-only, disposable lens market.

PMID- 22853743
TI  - Clopidogrel versus aspirin in patients with atherothrombosis: a CAPRIE-based cost
      effectiveness model for Greece.
AB  - BACKGROUND: Atherothrombosis represents a leading cause of morbidity and
      mortality worldwide. Given the prominent role of platelet aggregation in
      atherothrombosis, antiplatelet therapy forms the cornerstone of treatment, with
      proven efficacy in the secondary prevention of atherothrombotic events. Although
      clopidogrel seems to be superior to aspirin in terms of risk reduction for an
      atherothrombotic event, whether this clinical advantage is cost effective in
      Greece is unknown. OBJECTIVE: The aim of this study was to conduct a cost
      effectiveness analysis comparing clopidogrel with aspirin in the secondary
      prevention of atherothrombotic events in patients with peripheral artery disease,
      a recent stroke or a recent myocardial infarction, from the third-party-payer
      perspective in Greece. METHODS: A Markov model with a 6-month cycle length was
      developed. Transition probabilities used in the model were obtained from the
      event rates reported in the CAPRIE trial. The effect of clopidogrel was applied
      only during the first 2 years of the model. Utility data were used to estimate
      quality-adjusted life-years (QALYs). Costs (for the year 2012) assigned to each
      health state included antiplatelet treatment cost, cost for the management of
      adverse events related to antiplatelet therapy and the direct healthcare cost of
      patients (i.e. concomitant medication, hospitalization, outpatient visits,
      rehabilitation, laboratory and imaging diagnostic examinations as well as
      interventions) in the acute and follow-up phase, separately. The incremental cost
      effectiveness ratio (ICER) was calculated for life-years (LYs) and QALYs,
      separately. A probabilistic sensitivity analysis was conducted in order to
      evaluate the impact of the variation that characterizes the majority of model
      parameters to the cost-effectiveness results. RESULTS: The Markov analysis
      revealed that the discounted survival was 11.83 (95% CI 11.40, 12.22) years and
      12.17 (95% CI 11.75, 12.55) years in the aspirin and clopidogrel treatment
      groups, respectively, a difference of 0.34 (95% CI 0.09, 0.618) LYs. The
      corresponding discounted QALYs were 8.63 (95% CI 8.34, 8.90) and 8.84 (95% CI
      8.54, 9.10), respectively, a difference of 0.21 (95% CI 0.05, 0.37) QALYs. The
      cumulated lifetime costs per patient were ?20 678 (95% CI 19 675, 21 724) and ?21
      688 (95% CI 20 649, 22 773), for aspirin and clopidogrel treatment arm,
      respectively. The ICER for clopidogrel was calculated to be ?4038 (95% CI 2743,
      7837) for each LY saved and ?5518 (95% CI 3358, 12 921) for each QALY saved.
      CONCLUSION: The analysis indicates that clopidogrel is cost effective for the
      secondary prevention of atherothrombotic events in the Greek setting. These
      findings are in line with those reported in other European countries.

PMID- 22853744
TI  - Alcohol reform in Viet Nam: confronting rising consumption, injury and harm.

PMID- 22853745
TI  - Carbohydrate-derived hydrothermal carbons: a thorough characterization study.
AB  - Hydrothermal carbonization (HTC) is an aqueous-phase route to produce carbon
      materials using biomass or biomass-derived precursors. In this paper, a
      comprehensive physicochemical and textural characterization of HTC materials
      obtained using four different precursors, namely, xylose, glucose, sucrose, and
      starch, is presented. The development of porosity in the prepared HTC materials
      as a function of thermal treatment (under an inert atmosphere) was specifically
      monitored using N(2) and CO(2) sorption analysis. The events taking place during
      the thermal treatment process were studied by a combined
      thermogravimetric/infrared (TGA-IR) measurement. Interestingly, these inexpensive
      biomass-derived carbon materials show good selectivity for CO(2) adsorption over
      N(2) (CO(2)/N(2) selectivity of 20 at 273 K, 1 bar and 1:1 gas composition).
      Furthermore, the elemental composition, morphologies, degree of structural order,
      surface charge, and functional groups are also investigated.

PMID- 22853747
TI  - 30 years of immunomodulation by intravenous immunoglobulin.

PMID- 22853746
TI  - Overload and neovascularization of shoulder tendons in volleyball players.
AB  - BACKGROUND: In overhead sports like volleyball, the onset of a rotator cuff
      tendinopathy due to functional overload is a common observation. An
      angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater
      anaerobic metabolism occurs in critical zones of the tendon with a lower degree
      of vascularization; this would induce collagen and extracellular matrix
      degradation, that could then trigger a compensatory neovascularization response.
      We performed a clinical observational study of 80 elite volleyball players,
      monitoring the perfusion values of the supraspinatus tendons by oximetry.
      RESULTS: No statistically significant differences were found between the oximetry
      data and age, sex or years of sports activity, nor when comparing the right and
      left arm or the dominant and non-dominant arm. A statistically significant
      difference was found for the dominant arm values in relation to the competitive
      role, higher values being obtained in outside hitters (62.7%) than middle hitters
      (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players
      (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p >
      0.05). CONCLUSIONS: The different tendon vascularization values found in players
      with different roles in the team may be attributed to a response to the specific
      biomechanical demands posed by the different overhead throwing roles.

PMID- 22853748
TI  - Immunotherapy for Type 1 diabetes: getting beyond a negative first impression.

PMID- 22853749
TI  - Maternal antibodies as an immunotherapeutic strategy in the newborn.

PMID- 22853751
TI  - Tumor-associated macrophages: from cancer supporters to tumoricidal effectors.

PMID- 22853752
TI  - Concurrent HER2 vaccination and inhibition of kinase activity: safety and
      immunogenicity.
AB  - Passive immunotherapy with the monoclonal antibody trastuzumab and tyrosine
      kinase activity inhibition with lapatinib are HER2-targeted therapies used in the
      clinic for the treatment of HER2-overexpressing breast cancers. Unfortunately,
      the therapeutic efficacy of both these therapies is abolished by primary and
      acquired tumor resistance. Active immunotherapy against HER2, which, thanks to
      trastuzumab, is a clinically validated tumor-associated antigen, might provide an
      alternative therapeutic strategy for HER2-overexpressing breast cancers. This
      Phase I study of HER2 immunotherapy with concomitant lapatinib treatment in 12
      patients with metastatic breast cancer resistant to trastuzumab demonstrates the
      feasibility and safety of concurrent vaccination against HER2 and inhibition of
      HER1 and HER2 kinases. However, it is inconclusive regarding the effect of
      lapatinib on the immune responses induced by dHER2/AS15; vaccination triggered
      variable levels of anti-HER2 antibodies in all the patients, but a HER2-specific
      T-cell response was detected in one patient only. Since the presence of Tregs in
      these patients was not assessed, it remains unclear whether lapatinib and/or
      Tregs account for the near absence of a T-cell response.

PMID- 22853753
TI  - Treg infiltration in glioma: a hurdle for antiglioma immunotherapy.
AB  - Tregs play a crucial role in glioma-mediated immunosuppression; hence, tackling
      the Treg population in patients with malignant glioma could improve the clinical
      success rate of antiglioma immunotherapy. Therefore, it is of high importance to
      elucidate the mechanisms responsible for Treg recruitment and retention within
      the glioma microenvironment. The current paper demonstrates that, in addition to
      preferential chemoattraction, glioma-derived soluble factors can also induce
      preferential Treg proliferation and survival. These data identify new targets for
      Treg modulating strategies.

PMID- 22853754
TI  - A neoadjuvant biochemotherapy approach to stage III melanoma: analysis of
      surgical outcomes.
AB  - AIMS: Completion lymph node dissection (CLND) and adjuvant therapy are
      recommended for node-positive melanoma patients. We sought to analyze our
      institution's experience with neoadjuvant biochemotherapy in stage III patients.
      METHODS: Clinical information was extracted from a retrospective database on
      stage III melanoma patients. Eligible patients received two cycles of
      biochemotherapy prior to their CLND. RESULTS: There were 153 patients available
      for analysis. The average tumor depth was 2.5 mm. More than half of all patients
      presented with sentinel lymph node-positive disease. Surgical complications
      occurred in 23% of patients. Patients who experienced an adverse event during
      their neoadjuvant therapy had a worse overall survival when compared with those
      who did not (p = 0.005). CONCLUSION: Our data suggest that aggressive neoadjuvant
      treatment prior to CLND does not impact surgical complications. Our surgical
      outcomes are similar to the current literature when adjuvant therapy is used in
      stage III melanoma. The inability to tolerate neoadjuvant therapy in stage III
      melanoma is a negative prognostic indicator.

PMID- 22853755
TI  - Adjunct immune therapy of first-diagnosed TB, relapsed TB, treatment-failed TB,
      multidrug-resistant TB and TB/HIV.
AB  - AIM: To evaluate the effect of an adjunct immunotherapy in randomized double
      blind, placebo-controlled Phase IIb trial involving 123 TB patients. METHODS:
      Patients were randomly allocated into two arms: one (n = 62) received a once
      daily pill of V-5 ImmunitorTM (V5) and the other (control; n= 61) received
      placebo for 30 days in addition to first- or second-line TB drugs administered
      under directly observed therapy. The subjects in V5 and placebo arms had first
      diagnosed, relapsed, treatment-failed and multidrug-resistant TB at ratios of
      17:21:11:13 and 20:19:14:8, respectively; among them, ten and seven had HIV
      coinfection, respectively. RESULTS: After 1 month, 55 out of 62 patients (88.7%)
      became sputum smear-negative in the V5 arm (p < 0.0001), whereas in the placebo
      group, nine out of 61 (14.8%) had converted. The conversion rate among V5
      recipients was similar, regardless of whether TB was drug-sensitive, drug
      resistant or with HIV. V5 downregulated TB-associated inflammation, as shown by
      the normalization of elevated leukocyte counts (8.7 vs 6.3 * 10 (9)/l; p <
      0.0001) and decreased erythrocyte sedimentation rate (22.8 vs 12.6 mm/h; p <
      0.0001), whereas among placebo recipients, changes were smaller (8.9 vs 8.2 * 10
      (9)/l and 25.1 vs 19.9 mm/h). Thirty three (54.1%) placebo patients gained on
      average 0.8 kg (p = 0.0002); by contrast, 57 (91.9%) out of 62 patients in the V5
      group gained a mean weight of 2.9 kg (p < 0.0001). No adverse side effects or
      reactivation of TB were seen at any time. CONCLUSION: V5 is safe and effective as
      an immune adjunct to chemotherapy for TB and can potentially reduce the treatment
      duration down to 1 month.

PMID- 22853756
TI  - Effects of chitosan and its derivative added to water on immunological
      enhancement and disease control.
AB  - BACKGROUND: An immune system is a system of biological structures and processes
      within an organism that protects against diseases by identifying and killing
      pathogens and tumor cells. Development of novel natural immune enhancers is an
      urgent issue. METHODS: In experiment 1, Newcastle disease antibody titer, levels
      of IL-6, IL-10 and IFN-gamma, and changes in CD3(+), CD4(+) and CD8(+) cells were
      analyzed. In experiment 2, diarrhea, respiratory symptoms and mortality of
      broilers were measured. RESULTS: In experiment 1, the results showed that the
      immune response, such as Newcastle disease antibody and CD4(+) T cells, would be
      significantly activated by feeding with chitosan and its derivative during 27
      days. In experiment 2, the results demonstrated that diarrhea, respiratory
      symptoms and the mortality of the commercial medicine treatment group were
      decreased, with infection days increased. However, the mortality of broilers was
      significantly decreased, while feed intake and weight gain of the birds were
      significantly increased in the group treated with chitosan and its derivative as
      compared with other groups. CONCLUSION: Chitosan and its derivative have strong
      potential in immune enhancement and disease control, and can be used as a feed
      additive.

PMID- 22853757
TI  - Dendritic cell engineering for tumor immunotherapy: from biology to clinical
      translation.
AB  - Dendritic cells (DCs) are the most potent APCs, with the ability to orchestrate a
      repertoire of immune responses. DCs play a pivotal role in the initiation,
      programming and regulation of tumor-specific immune responses, as they are poised
      to take up, process and present tumor antigens to naive or effector T
      lymphocytes. Although, to an extent, DC-based immunotherapeutic strategies have
      successfully induced specific anti-tumor responses in animal models, their
      clinical efficacy has rarely been translated into the clinic. This article
      attempts to present a complete picture of recent developments of DC-based
      therapeutic strategies addressing multiple components of tumor immunoenvironment.
      It also showcases certain practical intricacies in order to explore novel
      strategies for providing new impetus to DC-based cancer vaccination.

PMID- 22853758
TI  - The sweet side of tumor immunotherapy.
AB  - Carbohydrate signatures on tumor cells have functional implications in tumor
      growth and metastasis and constitute valuable tools in cancer diagnosis and
      immunotherapy. Increasing data regarding the mechanisms by which they are
      recognized by the immune system are facilitating the design of more efficient
      immunotherapeutic protocols based on cancer-associated glycan structures. Recent
      molecular and proteomic studies revealed that carbohydrates are recognized, not
      only by B cells and antibodies, but also by cells from the innate arm of
      immunity, as well as by T cells, and are able to induce specific T-cell immunity
      and cytotoxicity. In this review, we discuss and update the different strategies
      targeting tumor-associated carbohydrate antigens that are being evaluated for
      antitumor immunotherapy, an approach that will be highly relevant, especially
      when combined with other strategies, in the future fight against cancer.

PMID- 22853759
TI  - Diagnosis and treatment of pemphigus.
AB  - Pemphigus is an autoimmune bullous disease, in which autoantibodies react with
      the cell-cell adhesion structures, desmosomes, causing blisters and erosions on
      the oral mucosa and skin. Pemphigus is divided into two major subtypes: pemphigus
      vulgaris and pemphigus foliaceus. Oral corticosteroids are the primary treatment
      modality for pemphigus, while other therapeutic options, such as steroid pulse
      therapy, immunosuppressants, intravenous immunoglobulins, plasmapheresis and anti
      CD20 monoclonal antibody therapy, are occasionally employed. Immunosuppressants
      used to treat pemphigus include azathioprine, cyclophosphamide, cyclosporine,
      mycophenolate mofetil and mizoribine. In this review, we summarize the current
      concepts of immunotherapy for the treatment of pemphigus in the Japanese
      population.

PMID- 22853761
TI  - [Approach to perinatal mortality in the Netherlands: outcomes of a systematic
      expert study].
AB  - In 2009 the Minister of Health, Welfare and Sport ordered several measures to
      reduce the high perinatal mortality in the Netherlands. One of these was the
      carrying out of a descriptive study into pregnancy and birth in which the
      systematic consultation of experts played an important role. The main aims were
      to produce a list of subjects to study and to prioritize scientific research. In
      addition, representatives of the scientific committees of the professional groups
      involved and the heads of perinatology centres were also consulted. The 25 most
      important resulting research themes pertained to (a) early detection of risks
      during the preconceptional period, pregnancy and parturition, (b) recognition and
      tackling of societal, psychosocial, social and socio-economic risk factors, and
      (c) a more extensive and risk-led collaboration between all healthcare workers
      within the Dutch obstetric healthcare system. This study contributed to the study
      agenda of the Netherlands Organization for Health Research and Development
      (ZonMw) which resulted in a widely supported, specialty transcending research
      programme on all aspects of pregnancy and birth.

PMID- 22853762
TI  - [Unexplained anaemia in men: be aware of hypogonadism].
AB  - Unexplained anaemia is not uncommon. We present two male patients suffering from
      longstanding mild anaemia, for which no cause could be found. We performed an
      extensive analysis, but there were no signs of malignant disease, chronic
      inflammation, renal failure, hypothyroidism, myelodysplastic syndrome, haemolysis
      or nutritional deficiencies. However, both patients had symptoms of hypogonadism,
      confirmed by biochemical testing. The 56-year-old man known with metabolic
      syndrome turned out to have secondary hypogonadism without a pituitary tumour and
      the 75-year-old man had primary hypogonadism. After exclusion of prostate
      carcinoma, testosterone substitution therapy was started in both patients, which
      improved their haematocrits and sexual and general well-being substantially.
      Testosterone exerts anabolic effects in multiple organ systems; in bone marrow it
      potentiates the stimulatory effect of erythropoietin on erythropoiesis. Primary
      hypogonadism frequently occurs in elderly patients, while secondary hypogonadism
      is frequently seen in middle-aged men with type 2 diabetes mellitus and obesity.

PMID- 22853763
TI  - [Giant haemangioma of the liver: diagnosis and treatment].
AB  - A liver haemangioma is a benign, usually small tumour comprised of blood vessels,
      which is often discovered coincidentally; giant haemangiomas are defined as
      haemangiomas larger than 5 cm. The differential diagnosis includes other
      hypervascular tumours, such as hepatocellular adenoma, hepatocellular carcinoma,
      metastasis of a neuro-endocrine tumour or renal cell carcinoma.- The diagnosis is
      based on abdominal ultrasonography and can be confirmed by a CT or MR scan. A
      wait-and-see approach is justified in patients without symptoms or with minimal
      symptoms, even in the presence of a giant haemangioma. Surgical resection of a
      giant haemangioma is only necessary when the preoperative diagnosis is
      inconclusive, or when the haemangioma leads to mechanical symptoms or
      complications. Extirpation is the only effective form of treatment of the giant
      haemangioma; enucleation is preferred over partial liver resection. A known
      complication of a giant haemangioma is the occurrence of disseminated
      intravascular coagulation, the Kasabach-Merritt syndrome; intervention is then
      demanded.

PMID- 22853764
TI  - [A boy with a painful knee: bone tumour or stress fracture?].
AB  - BACKGROUND: The symptoms of a stress fracture are almost identical to those of
      most bone tumours. Even with the use of various imaging techniques, it can be
      difficult to establish the correct diagnosis. Although a primary bone tumour
      requires early treatment to improve its prognosis, the discriminative factor in
      the diagnosis of a stress fracture is its clinical development over time. CASE
      DESCRIPTION: A 10-year-old boy was referred to our outpatient clinic on the
      suspicion of a primary bone tumour in his right tibia. CONCLUSION: A case was
      once described in this journal in which a stress fracture had eventually led to
      an amputation. The suspicion of primary bone tumour often marks the start of a
      long and intense diagnostic course. A stress fracture is the major diagnostic
      pitfall when there is a suspicion of such a tumour. If doubts persist after a
      diagnostic work-up by imaging, consultation with the Bone Tumour Committee is
      indicated. The patient can also be quickly referred to a centre specialised in
      treating bone tumours, as was the case in this article.

PMID- 22853765
TI  - [Public healthcare occupations--insight into size and composition is limited].
AB  - OBJECTIVE: To gain insight into the size and composition of the various groups of
      professionals operating in the Dutch public health sector in order to steer
      development within these groups and to improve quality and efficiency in public
      healthcare. DESIGN: Document analysis. METHOD: Analysis of data from 7 reports
      published between 2003 and 2010, focussing on descriptions of working fields,
      (definitions of) professions and roles and total numbers. RESULTS: By combining
      the data from 7 reports, we were able to estimate that the total size of all
      professional groups operating in the public healthcare sector is 12,000 FTE. This
      is an imprecise estimation because delimitation of the workforce, the occupations
      and roles selected and data collection methods used during the analyses was not
      all the same. Per analysis, the delimitation of the working fields ranged, for
      example, from all municipal health services to a broad selection of facilities
      and organisations. The roles included varied from 1 to more than 15. The only
      professionals for whom we could make use of data from a database for compulsory
      registration were the specialists in social medicine. CONCLUSION: Despite 7
      reports in 7 years, we still have insufficient insight into the size and
      composition of the public health workforce in the Netherlands. Whether or not
      current capacity is sufficient in relation to the desired levels of quality and
      efficiency, or will be in the future, is therefore unevaluable.

PMID- 22853766
TI  - [Obesity: more nurture than nature].
AB  - Hereditary factors as a cause of obesity have long been a subject of interest.
      The authors of another article in the Netherlands Journal of Medicine propose
      that 75% of differences in BMI are determined by heredity. However, these
      estimates differ quite considerably from study to study. In addition even though
      the genetic makeup of humans has not changed for tens of thousands of years, the
      number of obese people has greatly increased. The discovery of genetic reasons
      for obesity is certainly of scientific importance, but at population level
      nurture remains the most important.

PMID- 22853767
TI  - [Local recurrence after skin-sparing mastectomy].
AB  - On average, 250 skin-sparing mastectomies with immediate prosthetic
      reconstruction are performed in the Dutch Antoni van Leeuwenhoek Hospital each
      year. We report on two breast cancer patients (46 and 53 years old) who each
      developed a local recurrence at the entry site of the core needle biopsy after
      skin-sparing mastectomy with immediate prosthetic reconstruction. In hindsight,
      the most likely cause for these recurrences was the fact that one of the entry
      sites for the core needle biopsies was not marked preoperatively, and thus not
      excised during surgery. These examples emphasise the need for accurate
      documentation of the locations of these entry sites, followed by their excision,
      in patients undergoing skin-sparing mastectomy for invasive breast cancer.

PMID- 22853768
TI  - [The meta-analysis of data from individual patients].
AB  - An IPD (Individual Participant Data) meta-analysis requires collecting original
      individual patient data and calculating an estimated effect based on these data.
      The use of individual patient data has various advantages: the original data and
      the results of published analyses are verified, comparability between studies in
      terms of definitions, coding and analyses is increased, the number of options for
      performing sub-group analyses becomes greater, and it becomes possible to conduct
      more complex statistical analyses, such as the pooling of time-dependent data and
      multivariate regression analyses. In an IPD meta-analysis, additional information
      can be used which was not mentioned in the original article, for example, data
      from long-term follow-up. Improvements to this methodology are still possible;
      for example, to find the right balance between sufficient power to detect
      clinically relevant subgroup effects and minimizing the risk of false-positive
      findings. Readers can evaluate an IPD meta-analysis on various factors, including
      the reason for the choice for an IPD meta-analysis, the method used to identify
      and select the studies, and the number of approached authors that made their data
      available.

PMID- 22853769
TI  - [Determining burn depth: clinical assessment and laser Doppler imaging].
AB  - Early accurate determination of burn depth is important to determine the optimal
      treatment of burns. The method most used to determine burn depth is clinical
      assessment. This is a cheap method, but not the most accurate. Laser Doppler
      imaging (LDI) is a technique with which a more accurate (>95%) estimate of burn
      depth can be made by measuring the dermal perfusion. It is hypothesised that the
      introduction of LDI will lead to quicker decisions as to whether or not to
      operate, possibly leading to a shorter length of hospital stay and lower medical
      costs. To test this hypothesis, a multicentre randomized controlled trial is
      presently being conducted in the Dutch burn centres.

PMID- 22853770
TI  - [Precise staging of colon cancer is indeed useful].
AB  - According to a recent publication, an increase in the number of lymph nodes
      evaluated by pathologists in colon cancer specimens has not resulted in better
      staging. Over the years, more lymph nodes have been evaluated; however, not more
      patients were classified as being node-negative. For this reason, the authors
      argue that the number of lymph nodes evaluated is not a good quality indicator.
      We disagree. In our opinion, better staging would lead to better survival in node
      negative patients, which was indeed described by Parsons et al. The relatively
      low disease-staging score in patients with colon cancer in more recent years
      could be explained by an increase in screening programmes. Dutch data support
      this explanation.

PMID- 22853771
TI  - [A young man with recurrent chest pain].
AB  - BACKGROUND: Pericarditis is seen quite often in daily clinical practice. It is a
      condition that is fairly easy to diagnose, but which frequently recurs. CASE
      DESCRIPTION: A 23-year-old man suffered from recurring episodes of chest pain
      which, following further investigation, appeared to be a result of pericarditis.
      MRI revealed indications for acute exacerbation of chronic pericarditis.
      Additional investigation showed no underlying cause for the pericarditis. After
      long-term medication with calcium carbasalate and colchicine there was no
      recurrence and the patient was able to function as before. CONCLUSION: Chest pain
      in young people can be a symptom of pericarditis. This condition quite often
      recurs, but in most patients no underlying cause is revealed. Adequate medication
      with calcium carbasalate and colchicine reduces the chance of recurrence.

PMID- 22853772
TI  - [Screening of athletes prevents sudden cardiac death].
AB  - The sudden cardiac death (SCD) of an athlete is always a dramatic event, and one
      wonders if it could have been prevented by pre-participation cardiovascular
      screening. For years now, a pro/con debate has been taking place on the pre
      participation screening of athletes: the method, who is responsible, cost
      effectiveness, obligatory or voluntary screening. In this pro-article, which
      agrees with the "sudden cardiac death can be prevented by routinely pre
      participation cardiovascular screening"-standpoint, the unique Italian experience
      is the best argument for the support of screening. This study clearly
      demonstrated a reduction in SCD in those athletes who were screened in accordance
      with Italian law.

PMID- 22853773
TI  - [Screening of athletes is undesirable].
AB  - The sudden demise of an athlete invariably leads to calls for prevention.
      Although few screening programmes live up to expectations, the 2005 European
      Society of Cardiology consensus statement contains a recommendation for routine
      pre-participation screening of asymptomatic young athletes. As the incidence of
      sudden cardiac death (SCD) in this group is very low (< 2 per 100,000 per year),
      and no test reliably identifies persons at an increased risk of SCD, the Health
      Council of the Netherlands advised against mandatory screening. It seems prudent,
      however, to consider other strategies for reducing the occurrence of exercise
      related cardiac death, e.g. by stimulating prompt resuscitation efforts and,
      perhaps also focusing on the rapidly growing group of senior athletes at
      increased risk of acute cardiac (mainly coronary) events, as this group may
      benefit from the recent advances in CT imaging of the coronary arteries.

PMID- 22853774
TI  - A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis
      patients: clinical and genetic features.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an adult-onset Idiopathic
      Interstitial Pneumonia (IIP) usually diagnosed between age 50 to 70 years.
      Individuals with Familial Pulmonary Fibrosis (FPF) have at least one affected
      first or second-degree relative and account for 0.5-20% of cases. METHODS: We
      ascertained and collected DNA samples from a large population-based cohort of IPF
      patients from Newfoundland, Canada. For each proband, a family history was
      documented and medical records were reviewed. Each proband was classified as
      familial (28 patients) or sporadic (50 patients) and all 78 probands were
      screened for variants in four highly penetrant, adult-onset PF genes (SFTPC,
      SFTPA2, TERT,TERC). RESULTS: Seventy-eight IPF probands were enrolled of whom 28
      (35.9%) had a positive family history. These 28 familial patients led to the
      recruitment of an additional 49 affected relatives (total of 77 FPF patients). By
      age 60 years, 42% of the familial cohort had been diagnosed with PF compared with
      only 16% of the sporadic patient collection (chi2 = 8.77, p = 0.003). Mean age of
      diagnosis in the familial group was significantly younger than the sporadic group
      (61.4 years vs. 66.6 yrs, p = 0.012) with a wider age range of diagnosis (19-92
      years compared with 47-82 years). Thirty-three of 77 (42.8%) FPF patients had a
      tissue diagnosis and all but five had usual interstitial pneumonia histology.
      Compared with other published case series, the familial IIP histologies were more
      homogeneous. Three of 28 familial probands (10.7%) and none of the 50 sporadic
      probands had pathogenic variants in the four genes tested. All three familial
      probands had mutations in TERT. Other phenotypes associated with telomerase
      deficiency were present in these families including cirrhosis, bone marrow
      hypoplasia and premature graying. Telomere length assays were performed on
      mutation carriers from two families and confirmed telomere-related deficiency.
      CONCLUSION: The proportion of familial cases in our cohort is higher than any
      previously reported estimate and we suggest that this is due to the fact that
      Newfoundland cohort is ethnically homogeneous and drawn from a founder
      population. In our patient collection, diagnosis with IPF prior to age 45 years
      predicted familial disease. In two of the three TERT mutation families, the
      pedigree appearance is consistent with genetic anticipation. In the other 25 FPF
      families negative for mutations in known PF genes, we did not identify other
      telomerase associated medical problems (bone marrow dysfunction, cirrhosis) and
      we hypothesize that there are novel PF genes segregating in our population.

PMID- 22853776
TI  - Theoretical study of the regioselectivity of the interaction of 3-methyl-4
      pyrimidone and 1-methyl-2-pyrimidone with Lewis acids.
AB  - A density functional theory (DFT) study is performed to determine the stability
      of the complexes formed between either the N or O site of 3-methyl-4-pyrimidone
      and 1-methyl-2-pyrimidone molecules and different ligands. The studied ligands
      are boron and alkali Lewis acids, namely, B(CH(3))(3), HB(CH(3))(2),
      H(2)B(CH(3)), BH(3), H(2)BF, HBF(2), BF(3), Li(+), Na(+), and K(+). The acids are
      divided into two groups according to their hardness. The reactivity predictions,
      according to the molecular electrostatic potential (MEP) map and the natural bond
      orbital (NBO) analysis, are in agreement with the calculated relative
      stabilities. Our findings reveal a strong regioselectivity with borane and its
      derivatives preferring the nitrogen site in both pyrimidone isomers, while a
      preference for oxygen is observed for the alkali acids in the 3-methyl-4
      pyrimidone molecule. The complexation of 1-methyl-2-pyrimidone with these hard
      alkali acids does not show any discrimination between the two sites due to the
      presence of a continuous delocalized density region between the nitrogen and the
      oxygen atoms. The preference of boron Lewis acids toward the N site is due to the
      stronger B-N bond as compared to the B-O bond. The influence of fluorine or
      methyl substitution on the boron atom is discussed through natural orbital
      analysis (NBO) concentrating on the overlap of the boron empty p-orbital with the
      F lone pairs and methyl hyperconjugation, respectively. The electrophilicity of
      the boron acids gives a good overall picture of the interaction capabilities with
      the Lewis base.

PMID- 22853775
TI  - Consequences and countermeasures in a nuclear power accident: Chernobyl
      experience.
AB  - Despite the tragic accidents in Fukushima and Chernobyl, the nuclear power
      industry will continue to contribute to the production of electric energy
      worldwide until there are efficient and sustainable alternative sources of
      energy. The Chernobyl nuclear accident, which occurred 26 years ago in the former
      Soviet Union, released an immense amount of radioactivity over vast territories
      of Belarus, Ukraine, and the Russian Federation, extending into northern Europe,
      and became the most severe accident in the history of the nuclear industry. This
      disaster was a result of numerous factors including inadequate nuclear power
      plant design, human errors, and violation of safety measures. The lessons learned
      from nuclear accidents will continue to strengthen the safety design of new
      reactor installations, but with more than 400 active nuclear power stations
      worldwide and 104 reactors in the Unites States, it is essential to reassess
      fundamental issues related to the Chernobyl experience as it continues to evolve.
      This article summarizes early and late events of the incident, the impact on
      thyroid health, and attempts to reduce agricultural radioactive contamination.

PMID- 22853777
TI  - A yeast expression system for functional and pharmacological studies of the
      malaria parasite Ca2+/H+ antiporter.
AB  - BACKGROUND: Calcium (Ca2+) signalling is fundamental for host cell invasion,
      motility, in vivo synchronicity and sexual differentiation of the malaria
      parasite. Consequently, cytoplasmic free Ca2+ is tightly regulated through the co
      ordinated action of primary and secondary Ca2+ transporters. Identifying
      selective inhibitors of Ca2+ transporters is key towards understanding their
      physiological role as well as having therapeutic potential, therefore screening
      systems to facilitate the search for potential inhibitors are a priority. Here,
      the methodology for the expression of a Calcium membrane transporter that can be
      scaled to high throughputs in yeast is presented. METHODS: The Plasmodium
      falciparum Ca2+/H+ antiporter (PfCHA) was expressed in the yeast Saccharomyces
      cerevisiae and its activity monitored by the bioluminescence from apoaequorin
      triggered by divalent cations, such as calcium, magnesium and manganese. RESULTS:
      Bioluminescence assays demonstrated that PfCHA effectively suppressed induced
      cytoplasmic peaks of Ca2+, Mg2+ and Mn2+ in yeast mutants lacking the homologue
      yeast antiporter Vcx1p. In the scalable format of 96-well culture plates
      pharmacological assays with a cation antiporter inhibitor allowed the measurement
      of inhibition of the Ca2+ transport activity of PfCHA conveniently translated to
      the familiar concept of fractional inhibitory concentrations. Furthermore, the
      cytolocalization of this antiporter in the yeast cells showed that whilst PfCHA
      seems to locate to the mitochondrion of P. falciparum, in yeast PfCHA is sorted
      to the vacuole. This facilitates the real-time Ca2+-loading assays for further
      functional and pharmacological studies. DISCUSSION: The functional expression of
      PfCHA in S. cerevisiae and luminescence-based detection of cytoplasmic cations as
      presented here offer a tractable system that facilitates functional and
      pharmacological studies in a high-throughput format. PfCHA is shown to behave as
      a divalent cation/H+ antiporter susceptible to the effects of cation/H+
      inhibitors such as KB-R7943. This type of gene expression systems should advance
      the efforts for the screening of potential inhibitors of this type of divalent
      cation transporters as part of the malaria drug discovery initiatives and for
      functional studies in general. CONCLUSION: The expression and activity of the
      PfCHA detected in yeast by a bioluminescence assay that follows the levels of
      cytoplasmic Ca2+ as well as Mg2+ and Mn2+ lend itself to high-throughput and
      quantitative settings for pharmacological screening and functional studies.

PMID- 22853779
TI  - Patients with therapy-related myelodysplastic syndromes and acute myeloid
      leukemia share genetic features but can be separated by blast counts and
      cytogenetic risk profiles into prognostically relevant subgroups.

PMID- 22853780
TI  - Amnesiacs might get the gist: reduced false recognition in amnesia may be the
      result of impaired item-specific memory.
AB  - It is a common finding in tests of false recognition that amnesic patients
      recognize fewer related lures than healthy controls, and this has led to
      assumptions that gist memory is damaged in these patients (Schacter, Verfaellie,
      & Anes, 1997, Neuropsychology, 11; Schacter, Verfaellie, Anes, & Racine, 1998,
      Journal of Cognitive Neuroscience, 10; Schacter, Verfaellie, & Pradere, 1996,
      Journal of Memory and Language, 35). However, clinical observations find that
      amnesic patients typically hold meaningful conversations and make relevant
      remarks, and there is some experimental evidence highlighting preserved immediate
      recall of prose (Baddeley & Wilson, 2002, Neuropsychologia, 40; Gooding, Isaac, &
      Mayes, 2005, Neuropsychologia, 43; Rosenbaum, Gilboa, Levine, Winocur, &
      Moscovitch, 2009, Neuropsychologia, 47), which suggests that amnesiacs can get
      the gist. The present experiment used false recognition paradigms to assess
      whether the reduced rate of false recognition found in amnesic patients may be a
      consequence of their impaired item-specific memory. It examined the effect of
      increasing the item-specific memory of amnesic patient DA by bringing her to
      criterion on relevant study-lists and compared her performance on a false
      recognition paradigm with a group of 32 healthy young adults. Results indicated
      that when DA's item-specific memory was increased she was more able to gist and
      her performance was no different to the healthy young adults. Previous
      assumptions that gist memory is necessarily damaged in amnesia might therefore be
      revisited, since the reduced rate of false recognition could be caused by
      impaired item-specific memory. The experiment also highlights a positive
      relationship between item-specific and gist memory which has not previously been
      accounted for in false-recognition experiments. 

PMID- 22853778
TI  - Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome
      (22q11.2 deletion syndrome) and unaffected siblings.
AB  - BACKGROUND: Velo-cardio-facial syndrome (VCFS, MIM#192430, 22q11.2 Deletion
      Syndrome) is a genetic disorder caused by a deletion of about 40 genes at the
      q11.2 band of one copy of chromosome 22. Individuals with VCFS present with
      deficits in cognition and social functioning, high risk of psychiatric disorders,
      volumetric reductions in gray and white matter (WM) and some alterations of the
      WM microstructure. The goal of the current study was to characterize the WM
      microstructural differences in individuals with VCFS and unaffected siblings, and
      the correlation of WM microstructure with neuropsychological performance. We
      hypothesized that individuals with VCFS would have decreased indices of WM
      microstructure (fractional anisotropy (FA), axial diffusivity (AD) and radial
      diffusivity (RD)), particularly in WM tracts to the frontal lobe, and that these
      measures would be correlated with cognitive functioning. METHODS: Thirty-three
      individuals with VCFS (21 female) and 16 unaffected siblings (8 female)
      participated in DTI scanning and neuropsychological testing. We performed an
      atlas-based analysis, extracted FA, AD, and RD measures for 54 WM tracts (27 in
      each hemisphere) for each participant, and used MANOVAs to compare individuals
      with VCFS to siblings. For WM tracts that were statistically significantly
      different between VCFS and siblings (pFDR <0.05), we assessed the correlations
      between DTI and neuropsychological measures. RESULTS: In VCFS individuals as
      compared to unaffected siblings, we found decreased FA in the uncinate
      fasciculus, and decreased AD in multiple WM tracts (bilateral superior and
      posterior corona radiata, dorsal cingulum, inferior fronto-occipital fasciculus,
      superior longitudinal fasciculus, superior cerebellar peduncle, posterior
      thalamic radiation, and left anterior corona radiata, retrolenticular part of the
      internal capsule, external capsule, sagittal stratum). We also found significant
      correlations of AD with measures of executive function, IQ, working memory,
      and/or social cognition. CONCLUSIONS: Our results suggest that individuals with
      VCFS display abnormal WM connectivity in a widespread cerebro-anatomical network,
      involving tracts from/to all cerebral lobes and the cerebellum. Future studies
      could focus on the WM developmental trajectory in VCFS, the association of WM
      alterations with psychiatric disorders, and the effects of candidate 22q11.2
      genes on WM anomalies.

PMID- 22853781
TI  - Could transcranial direct current stimulation have unexpected additional benefits
      in the treatment of depressed patients?

PMID- 22853782
TI  - Could behavioral therapies target specific deficits in multiple sclerosis
      patients?

PMID- 22853784
TI  - Onabotulinum toxin A for the treatment of neurogenic detrusor overactivity due to
      spinal cord injury or multiple sclerosis.
AB  - Evidence for the efficacy and safety of intravesical onabotulinum toxin A
      (onabotA) injections has led to it being licensed in many countries in patients
      with urinary incontinence due to neurogenic detrusor overactivity resulting from
      spinal cord injury and multiple sclerosis, who are refractory or intolerant to
      the gold-standard treatment, anticholinergics. Owing to its mechanism of action,
      an inhibitory effect on acetylcholine release is obtained for up to 10 months,
      with a recommended dose of 200 units. Urinary tract infections and postvoid
      residual volume are the most prevalent side effects. In the case of residual
      volume, clean intermittent catheterization might be necessary. In patients with
      spinal cord injury and multiple sclerosis, it is recommended to evaluate the
      manual dexterity and cognitive function before onabotA injections, to ensure that
      the patient and caregiver are able to perform catheterization if necessary.
      OnabotA treatment has a beneficial effect not only on urinary symptoms but also
      on quality of life.

PMID- 22853785
TI  - News in aging and dementia at the 13th Pan American Congress of Neurology.
AB  - The Pan American Congress of Neurology was organized by the Bolivian Society of
      Neurology on behalf of the World Federation of Neurology in La Paz, Bolivia.
      Aging and dementia was one of the main congress tracks that has been highlighted
      in recent Latin American research in the field, focusing specifically on
      epidemiological studies, the economic cost of dementia and new Alzheimer's
      disease (AD) biomarkers. A 4-year follow-up study of AD biomarkers was discussed
      and a survey was conducted in Argentina on the opinion of the general population
      in relation to the clinical use of these biomarkers, and early diagnosis criteria
      of AD were presented. In parallel, a newly developed Neurology International
      Conference for Primary Care was run that was designed for the education of more
      than 350 general practitioners from all the regions of Bolivia.

PMID- 22853786
TI  - Finding gaps and building bridges in movement disorders.
AB  - Movement disorders are one of the most rapidly growing fields of neurology from
      both the clinical and neurobiological perspectives. Despite many recent advances
      in genetic, pathogenetic, clinical and therapeutic fields, several shortcomings
      remain in the diagnostic and therapeutic realms, with a plethora of challenges
      threatening further advances. Aimed at recognizing and bridging these knowledge
      gaps, the 2nd International Conference on Knowledge Gaps in Parkinson's Disease
      and Other Movement Disorders was held last February in Santa Margherita Ligure,
      Italy, with the support of the Movement Disorder Society and the Italian
      Association for Parkinson's Disease and Extrapyramidal Disorders. The 3-day
      symposium, which was attended by approximately 300 clinicians and researchers
      from around the world, gathered around 27 leading young and senior clinical
      scientists, each of whom addressed the field's main knowledge gaps and
      brainstormed on how to bridge or minimize their impact. This meeting report
      summarizes the topics that gathered the most attention from the speakers and the
      audience.

PMID- 22853788
TI  - D-serine and schizophrenia: an update.
AB  - Considering the lengthy history of pharmacological treatment of schizophrenia,
      the development of novel antipsychotic agents targeting the glutamatergic system
      is relatively new. A glutamatergic deficit has been proposed to underlie many of
      the symptoms typically observed in schizophrenia, particularly the negative and
      cognitive symptoms (which are less likely to respond to current treatments). D
      serine is an important coagonist of the glutamate NMDA receptor, and accumulating
      evidence suggests that D-serine levels and/or activity may be dysfunctional in
      schizophrenia and that facilitation of D-serine transmission could provide a
      significant therapeutic breakthrough, especially where conventional treatments
      have fallen short. A summary of the relevant animal data, as well as genetic
      studies and clinical trials examining D-serine as an adjunct to standard
      antipsychotic therapy, is provided in this article. Together, the evidence
      suggests that research on the next generation of antipsychotic agents should
      include studies on increasing brain levels of D-serine or mimicking its action on
      the NMDA receptor.

PMID- 22853789
TI  - Cognitive remediation for schizophrenia: current status, biological correlates
      and predictors of response.
AB  - Cognitive remediation (CR) is an increasingly studied behavioral intervention for
      improving illness-linked cognitive deficits in schizophrenia, with considerable
      promise for improving the disease outcome when offered in concert with other
      therapies. We present findings from a comprehensive, critical review of the
      extant literature on CR for schizophrenia. Conclusions from six meta-analyses
      presented to date are summarized, and existing CR interventions are categorized
      into three major classes: restorative, strategy-based and hybrid approaches. The
      crucial elements and empirical support for each class are presented. Studies of
      predictors of treatment response suggest that attention, motivation and clinician
      expertise, along with the measures of 'brain reserve', are key features of a
      positive treatment response. Lastly, findings from studies of neuroimaging
      indicate that CR is accompanied by structural and functional neural changes in
      key frontal and temporal brain regions.

PMID- 22853790
TI  - Special biological issues in the management of women with schizophrenia.
AB  - Schizophrenia is a debilitating and pervasive mental illness with devastating
      effects on psychological, cognitive and social wellbeing, and for which current
      treatment options are far from ideal. Gender differences and the influence of the
      female reproductive life cycle on the onset, course and symptoms of schizophrenia
      and the discovery of estrogen's remarkable psychoprotective properties in animal
      models led to the proposal of the 'estrogen protection hypothesis' of
      schizophrenia. This has fueled the recent successful investigation of estradiol
      as a potential adjuvant therapeutic agent in the management of schizophrenia in
      women. This review explains the scientific rationale behind the estrogen
      hypothesis and how it can be clinically utilized to address concerns unique to
      the care of women with schizophrenia.

PMID- 22853787
TI  - Modeling resilience to schizophrenia in genetically modified mice: a novel
      approach to drug discovery.
AB  - Complex psychiatric disorders, such as schizophrenia, arise from a combination of
      genetic, developmental, environmental and social factors. These vulnerabilities
      can be mitigated by adaptive factors in each of these domains engendering
      resilience. Modeling resilience in mice using transgenic approaches offers a
      direct path to intervention, as resilience mutations point directly to
      therapeutic targets. As prototypes for this approach, we discuss the three mouse
      models of schizophrenia resilience, all based on modulating glutamatergic
      synaptic transmission. This motivates the broader development of schizophrenia
      resilience mouse models independent of specific pathophysiological hypotheses as
      a strategy for drug discovery. Three guiding validation criteria are presented. A
      resilience-oriented approach should identify pharmacologically tractable targets
      and in turn offer new insights into pathophysiological mechanisms.

PMID- 22853791
TI  - Finding a biosignature for melancholic depression.
AB  - Melancholia is typified by features of psychomotor slowing, anxiety, appetite
      loss and sleep changes. It is usually observed in 20-30% of individuals meeting
      diagnostic criteria for major depressive disorder (MDD). There is currently no
      agreement on whether melancholic MDD represents a distinct entity defined by
      neurobiological as well as clinical features or, rather, a specifier for MDD.
      This situation is reflected in the revisions to DSM, including in the DSM-5 due
      for release in 2013. With this context in mind, the authors review the origins of
      the construct of melancholia in MDD, its theoretical grounding and the defining
      characteristics that arose from this research. The authors then outline the state
      of knowledge on the neurobiology of melancholia. This second aspect is
      illustrative of the National Institutes of Mental Health's research domain
      criteria initiative, which offers a framework for redefining constructs along
      neurobiological dimensions. The authors also consider the outlook for identifying
      a useful biosignature of melancholia.

PMID- 22853792
TI  - The relationship between oxidative stress and post-translational modification of
      the dopamine transporter in bipolar disorder.
AB  - Bipolar disorder (BD) has been consistently associated with altered levels of
      oxidative stress markers, although the cause and consequences of these
      alterations remain to be elucidated. One of the main hypotheses regarding the
      pathogenesis of mania involves increased dopaminergic transmission. In this
      review, the authors aim to discuss a potential mechanism by which increased
      oxidative stress inhibits the uptake of dopamine through the post-translational
      modification of the dopamine transporter and its implications for BD. Within the
      next 5 years, the authors believe that the mechanisms of dopamine transporter
      oxidation and its impact on the pathophysiology of BD will be elucidated, which
      may open avenues for the development of more specific interventions for the
      treatment of this debilitating illness.

PMID- 22853793
TI  - Internet-based psychological treatments for depression.
AB  - Major depression is highly prevalent, and is associated with high societal costs
      and individual suffering. Evidence-based psychological treatments obtain good
      results, but access to these treatments is limited. One way to solve this problem
      is to provide internet-based psychological treatments, for example, with
      therapist support via email. During the last decade, internet-delivered cognitive
      behavioral therapy (ICBT) has been tested in a series of controlled trials.
      However, the ICBT interventions are delivered with different levels of contact
      with a clinician, ranging from nonexisting to a thorough pretreatment assessment
      in addition to continuous support during treatment. In this review, the authors
      have found an evidence for a strong correlation between the degree of support and
      outcome. The authors have also reviewed how treatment content in ICBT varies
      among treatments, and how various therapist factors may influence outcome. Future
      possible applications of ICBT for depression and future research needs are also
      discussed.

PMID- 22853796
TI  - Saliva cortisol and male depressive syndrome in a community study. The
      Sudurnesjamenn study.
AB  - BACKGROUND: The degree and direction of hypothalamic-pituitary-adrenal (HPA)
      dysfunction to male mental health is unclear. AIMS: The aim of the study was to
      investigate the relationship between cortisol and male mental health. METHODS: In
      this community study, 534 males were screened, using the Beck Depression
      Inventory (BDI), Gotland Male Depression Scale (GMDS) and a general health
      questionnaire. Those with signs of depression (n = 65) and controls (n = 69) were
      evaluated in a psychiatric examination according to the DSM-IV criteria for
      depressive disorder (DD). In a sub-sample (n = 51) saliva cortisol was measured
      five times on a single day. RESULTS: Evening cortisol was significantly higher in
      untreated individuals with DD. Significantly higher evening cortisol (at 22 h)
      correlated also with a history of physical disorder, a history of any mental
      disorder and MADRS score >= 20 (Montgomery-Asberg Depression Rating Scale). High
      cortisol, measured as AUC (area under curve), correlated with a high MADRS score
      but not with any other health variable tested. Morning cortisol did not correlate
      with any health variable; however, cortisol awakening response (CAR) could not be
      investigated. The BDI and GMDS scores did not correlate with cortisol
      measurements. CONCLUSION: Evening saliva cortisol measurement seems most
      informative, as it correlates with male depressive syndrome in our study but
      replications with larger studies are needed.

PMID- 22853794
TI  - Molecular subgroups of medulloblastoma.
AB  - Recent efforts at stratifying medulloblastomas based on their molecular features
      have revolutionized our understanding of this morbidity. Collective efforts by
      multiple independent groups have subdivided medulloblastoma from a single disease
      into four distinct molecular subgroups characterized by disparate transcriptional
      signatures, mutational spectra, copy number profiles and, most importantly,
      clinical features. We present a summary of recent studies that have contributed
      to our understanding of the core medulloblastoma subgroups, focusing largely on
      clinically relevant discoveries that have already, and will continue to, shape
      research.

PMID- 22853797
TI  - Multi-institutional analysis of early glottic cancer from 2000 to 2005.
AB  - BACKGROUND: The purpose of this study is to analyze the outcome of patients with
      early glottic cancer (GC) treated with radiotherapy (RT) with or without
      chemotherapy at 10 institutions in the Tokai District, Japan. METHODS: Ten
      institutions combined data from 279 patients with T1-T2 GC treated with RT with
      or without chemotherapy between 2000 and 2005. The overall survival rate, disease
      specific survival rate, and local control rate were evaluated in 270 patients,
      except for incomplete cases due to issues such as discontinuation, using the
      method of Kaplan-Meier and compared using the log-rank test. Results were
      considered statistically significant at the level of p < 0.05. RESULTS: For 122
      patients, the tumors were classified as T1a, while 64 patients had T1b tumors,
      and 84 patients had T2 tumors. In three cases of T1 tumors, the subtype was
      unknown. Combined chemoradiotherapy (CRT) was administered during each stage, and
      various chemotherapy drugs and regimens were used. The median follow-up period
      was 55.4 months. The 5-year LC rates for T1a, Tb, and T2 tumors in all patients
      were 87.9%, 82.7%, and 74.1%, respectively. The difference between T1a and T2 was
      statistically significant (p = 0.016). The 5-year LC rates for T1a, Tb, and T2
      with CRT were 92.7%, 78.6%, and 80.7%, respectively, while the rates with
      radiation alone were 86.5%, 83.8%, and 64.4%, respectively. The difference
      between CRT and RT alone was not statistically significant in each stage.
      CONCLUSIONS: In this survey, CRT was performed for early GC at most institutions
      in clinical practice. Our data showed no statistical difference in the LC rates
      between CRT and RT alone in each stage. However, there was a tendency for the
      LCRs of the CRT group to be more favorable than those of the RT group in the T2
      stage.

PMID- 22853798
TI  - Activation of platelet protein kinase C by ultraviolet light B mediates platelet
      transfusion-related acute lung injury in a two-event animal model.
AB  - BACKGROUND: We recently reported that infusion of ultraviolet light B (UVB)
      exposed human platelets (HPs) can be the second event that mediates acute lung
      injury (ALI) in a two-event mouse model of transfusion-related acute lung injury
      (mTRALI). We have now identified changes in HPs induced by UVB light and
      responses of the recipient animal that mediate the mTRALI. STUDY DESIGN AND
      METHODS: Effects of UVB on HPs were monitored by flow cytometry and aggregation.
      HPs exposed to UVB, with or without inhibitors to specific biochemical pathways,
      were infused into lipopolysaccharide (LPS)-primed severe combined immunodeficient
      (SCID) mice. ALI was monitored by protein elevations in bronchoalveolar lavage
      fluid (BALF). RESULTS: UVB increased fibrinogen binding and potentiated HP
      aggregation. Infusion of UVB HPs into LPS-primed SCID mice led to macrophage
      inflammatory protein 2 (MIP-2) elevations in plasma and BALF and resulted in ALI.
      Protein kinase C (PKC) inhibitors prevented UVB-induced HP changes in vitro and
      reduced MIP-2 elevation and mTRALI in vivo. Blocking of fibrinogen binding to HP
      alphaIIbbeta3 with c7E3 monoclonal antibody prevented mTRALI. MIP-2 elevation in
      vivo in response to UVB HPs was essential for ALI since blocking of MIP-2
      receptor in vivo prevented mTRALI. CONCLUSION: PKC signaling mediates UVB-induced
      HP fibrinogen binding and aggregation in vitro. The host animal responds to an
      infusion of UVB HPs by MIP-2 elevation that mediates downstream mTRALI.
      Elucidation of molecular mechanisms in UVB HP-mediated mTRALI may provide insight
      into pulmonary adverse events reported with UV-irradiated pathogen-reduced
      platelets.

PMID- 22853799
TI  - Technical support and delegation to practice staff - status quo and (possible)
      future perspectives for primary health care in Germany.
AB  - BACKGROUND: Primary health care in industrialized countries faces major
      challenges due to demographic changes, an increasing prevalence of chronic
      diseases and a shortage of primary care physicians. One approach to counteract
      these developments might be to reduce primary care physicians' workload supported
      by the use of health information technology (HIT) and non-physician practice
      staff. In 2009, the U.S. Commonwealth Fund (CWF) conducted an international
      survey of primary care physicians which the present secondary descriptive
      analysis is based on. The aim of this analysis was twofold: First, to explore to
      what extend German primary care physicians already get support by HIT and non
      physician practice staff, and second, to show possible future perspectives.
      METHODS: The CWF questionnaire was sent to a representative random sample of
      1,500 primary care physicians all over Germany. The data was descriptively
      analyzed. Group comparisons regarding differences in gender and age groups were
      made by means of Chi Square Tests for categorical variables. An alpha-level of p
      < 0.05 was used for statistical significance. RESULTS: Altogether 715 primary
      care physicians answered the questionnaire (response rate 49%). Seventy percent
      of the physicians use electronic medical records. Technical features such as
      electronic ordering and access to laboratory parameters are mainly used. However,
      the majority does not routinely use technical functions for drug prescribing,
      reminder-systems for guideline-based interventions or recall of patients. Six
      percent of surveyed physicians are able to transfer prescriptions electronically
      to a pharmacy, 1% use email communication with patients regularly. Seventy-two
      percent of primary care physicians get support by non-physician practice staff in
      patient care, mostly in administrative tasks or routine preventive services. One
      fourth of physicians is supported in telephone calls to the patient or in patient
      education and counseling. CONCLUSION: Within this sample the majority of primary
      care physicians get support by HIT and non-physician practice staff in their
      daily work. However, the potential has not yet been fully used. Supportive
      technical functions like electronic alarm functions for medication or electronic
      prescribing should be improved technically and more adapted to physicians' needs.
      To warrant pro-active health care, recall and reminder systems should get refined
      to encourage their use. Adequately qualified non-physician practice staff could
      play a more active role in patient care. Reimbursement should not only be linked
      to doctors', but also to non-physician practice staff services.

PMID- 22853800
TI  - Exploring, refining, and validating the paradynamics QM/MM sampling.
AB  - The performance of the paradynamics (PD) reference potential approach in QM/MM
      calculations is examined. It is also clarified that, in contrast to some possible
      misunderstandings, this approach provides a rigorous strategy for QM/MM free
      energy calculations. In particular, the PD approach provides a gradual and
      controlled way of improving the evaluation of the free energy perturbation
      associated with moving from the EVB reference potential to the target QM/MM
      surface. This is achieved by moving from the linear response approximation to the
      full free energy perturbation approach in evaluating the free energy changes. We
      also present a systematic way of improving the reference potential by using
      Gaussian-based correction potentials along a reaction coordinate. In parallel, we
      review other recent adaptations of the reference potential approach, emphasizing
      and demonstrating the advantage of using the EVB potential as a reference
      potential, relative to semiempirical QM/MM molecular orbital potentials. We also
      compare the PD results to those obtained by direct calculations of the potentials
      of the mean force (PMF). Additionally, we propose a way of accelerating the PMF
      calculations by using Gaussian-based negative potentials along the reaction
      coordinate (which are also used in the PD refinement). Finally, we discuss
      performance of the PD and the metadynamics approaches in ab initio QM/MM
      calculations and emphasize the advantage of using the PD approach. 

PMID- 22853802
TI  - Dyotropic rearrangements of fused tricyclic beta-lactones: application to the
      synthesis of (-)-curcumanolide A and (-)-curcumalactone.
AB  - Dyotropic rearrangements of fused, tricyclic beta-lactones are described that
      proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged,
      spiro-gamma-butyrolactones. A unique example of this dyotropic process involves a
      fused bis-lactone possessing both beta- and delta-lactone moieties which enabled
      rapid access to the core structures of curcumanolide A and curcumalactone. Our
      current mechanistic understanding of the latter dyotropic process, based on
      computational studies, is also described. Other key transformations in the
      described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from
      a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione,
      respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed
      aldol-lactonization (NCAL) leading to a tricyclic beta-lactone, a Baeyer-Villiger
      oxidation in the presence of a beta-lactone, and highly facial-selective and
      stereocomplementary reductions of an intermediate spirocyclic enoate. The
      described dyotropic rearrangements significantly alter the topology of the
      starting tricyclic beta-lactone, providing access to complex spirocyclic
      cyclopentyl-gamma-lactones and bis-gamma-lactones in a single synthetic
      operation.

PMID- 22853801
TI  - New positron emission tomography (PET) radioligand for imaging sigma-1 receptors
      in living subjects.
AB  - sigma-1 receptor (S1R) radioligands have the potential to detect and monitor
      various neurological diseases. Herein we report the synthesis, radiofluorination,
      and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1
      yl)ethyl)benzo[d]thiazol-2(3H)-one ([(18)F]FTC-146, [(18)F]13). [(18)F]13 was
      synthesized by nucleophilic fluorination, affording a product with >99%
      radiochemical purity (RCP) and specific activity (SA) of 2.6 +/- 1.2 Ci/MUmol (n
      = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo
      autoradiography studies of [(18)F]13 in mice showed high uptake of the
      radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg
      haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of
      [(18)F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting
      that [(18)F]13 accumulation in mouse brain represents specific binding to S1Rs.
      These results indicate that [(18)F]13 is a promising candidate radiotracer for
      further evaluation as a tool for studying S1Rs in living subjects.

PMID- 22853803
TI  - Individual and district-level predictors of alcohol use: cross sectional findings
      from a rural mental health survey in Australia.
AB  - BACKGROUND: Excessive alcohol use is a significant problem in rural and remote
      Australia. The factors contributing to patterns of alcohol use have not been
      adequately explained, yet the geographic variation in rates suggests a potential
      contribution of district-level factors, such as socio-economic disadvantage,
      rates of population change, environmental adversity, and remoteness from
      services/population centres. This paper aims to investigate individual-level and
      district-level predictors of alcohol use in a sample of rural adults. METHODS:
      Using baseline survey data (N = 1,981) from the population-based Australian Rural
      Mental Health Study of community dwelling residents randomly selected from the
      Australia electoral roll, hierarchal logistic regression models were fitted for
      three outcomes: 1) at-risk alcohol use, indicated by Alcohol Use Disorders
      Identification Test scores >=8; 2) high alcohol consumption (> 40 drinks per
      month); and 3) lifetime consequences of alcohol use. Predictor variables included
      demographic factors, pre-dispositional factors, recent difficulties and support,
      mental health, rural exposure and district-level contextual factors. RESULTS:
      Gender, age, marital status, and personality made the largest contribution to at
      risk alcohol use. Five or more adverse life events in the past 12 months were
      also independently associated with at-risk alcohol use (Adjusted Odds Ratio [AOR]
      3.3, 99%CI 1.2, 8.9). When these individual-level factors were controlled for, at
      risk alcohol use was associated with having spent a lower proportion of time
      living in a rural district (AOR 1.7, 99%CI 1.3, 2.9). Higher alcohol consumption
      per month was associated with higher district-level socio-economic ranking,
      indicating less disadvantage (AOR 1.2, 99%CI 1.02, 1.4). Rural exposure and
      district-level contextual factors were not significantly associated with lifetime
      consequences of alcohol use. CONCLUSIONS: Although recent attention has been
      directed towards the potential adverse health effects of district or community
      level adversity across rural regions, our study found relatively few district
      level factors contributing to at-risk alcohol consumption after controlling for
      individual-level factors. Population-based prevention strategies may be most
      beneficial in rural areas with a higher socio-economic ranking, while individual
      attention should be focused towards rural residents with multiple recent adverse
      life events, and people who have spent less time residing in a rural area.

PMID- 22853804
TI  - Engaging patients in health care decisions in the emergency department through
      shared decision-making: a systematic review.
AB  - BACKGROUND: Many decisions in the emergency department (ED) may benefit from
      patient involvement, even though this setting has been considered least conducive
      to shared decision-making (SDM). OBJECTIVES: The objective was to conduct a
      systematic review to evaluate the approaches, methods, and tools used to engage
      patients or their surrogates in SDM in the ED. METHODS: Five electronic databases
      were searched in conjunction with contacting content experts, reviewing selected
      bibliographies, and conducting citation searches using the Web of Knowledge
      database. Two reviewers independently selected eligible studies that addressed
      patient involvement and engagement in decision-making in the ED setting via the
      use of decision support interventions (DSIs), defined as decision aids or
      decision support designed to communicate probabilistic information on the risks
      and benefits of treatment options to patients as part of an SDM process. Eligible
      studies described and assessed at least one of the following outcomes: patient
      knowledge, experiences and perspectives on participating in treatment or
      management decisions, clinician or patient satisfaction, preference for
      involvement and/or degree of engagement in decision-making and treatment
      preferences, and clinical outcomes (e.g., rates of hospital
      admission/readmission, rates of medical or surgical interventions). Two reviewers
      extracted data on study characteristics, methodologic quality, and outcomes. The
      authors also assessed the extent to which SDM interventions adhered to good
      practice for the presentation of information on outcome probabilities (eight
      probability items from the International Patient Decision Aid Standards
      Instrument [IPDASi]) and had comprehensive development processes. RESULTS: Five
      studies met inclusion criteria and were synthesized using a narrative approach.
      Each study was of satisfactory methodologic quality and used a DSI to engage
      patients or their surrogates in decision-making in the ED across four domains: 1)
      management options for children with small lacerations; 2) options for
      rehydrating children presenting with vomiting or diarrhea or both; 3) risk of
      bacteremia (and associated complications), tests, and treatment options for
      febrile children; and 4) short-term risk of acute coronary syndrome (ACS) in
      adults with low-risk nontraumatic chest pain. Three studies had poor IPDASi
      probabilities and development process scores and lacked development informed by
      theory or involvement of clinicians and patients in development and usability
      testing. Overall, DSIs were associated with improvements in patients' knowledge
      and satisfaction with the explanation of their care, preferences for involvement,
      and engagement in decision-making and demonstrated utility for eliciting
      patients' preferences and values about management and treatment options. Two
      computerized DSIs (designed to predict risk of ACS in adults presenting to the ED
      with chest pain) were shown to reduce health care use without evidence of harm.
      None of the studies reported lack of feasibility of SDM in the ED. CONCLUSIONS:
      Early investigation of SDM in the ED suggests that patients may benefit from
      involvement in decision-making and offers no empirical evidence to suggest that
      SDM is not feasible. Future work is needed to develop and test additional SDM
      interventions in the ED and to identify contextual barriers and facilitators to
      implementation in practice.

PMID- 22853805
TI  - Expression of sialic acids and other nonulosonic acids in Leptospira.
AB  - BACKGROUND: Sialic acids are negatively charged nine carbon backbone sugars
      expressed on mammalian cell surfaces. Sialic acids are part of a larger family of
      nonulosonic acid (NulO) molecules that includes pseudaminic and legionaminic
      acids. Microbial expression of sialic acids and other nonulosonic acids has been
      shown to contribute to host-microbe interactions in a variety of contexts,
      including participation in colonization, immune subversion, and behaviors such as
      biofilm formation, autoagglutination and motility. Previous research has
      suggested that some spirochetes may also express these molecules. RESULTS: Here
      we use a combination of molecular tools to investigate the presence of NulO
      biosynthetic gene clusters among clinical and saprophytic isolates of the genus
      Leptospira. Polymerase chain reaction and Southern blotting suggested that a
      variety of leptospires encoded NulO biosynthetic pathways. High performance
      liquid chromatography and mass spectrometry analyses provided biochemical
      evidence that di-N-acetylated NulO molecules are expressed at relatively high
      levels by L. interrogans serovar Lai strain 55601, and at lower levels by L.
      alexanderi serovar Manhao and L. fainei serovar Hurstbridge. Endogenous
      expression of N-acetylneuraminic acid (Neu5Ac, the most common sialic acid) was
      documented in L. interrogans serovar Copenhageni strain L1-130. Neu5Ac
      biosynthesis is also supported by a unique gene fusion event resulting in an
      enzyme with an N-terminal N-acetylneuraminic acid synthase domain and a C
      terminal phosphatase domain. This gene fusion suggests that L. interrogans uses a
      Neu5Ac biosynthetic pathway more similar to animals than to other bacteria.
      Analysis of the composition and phylogeny of putative NulO biosynthetic gene
      clusters in L. interrogans serovar Lai and serovar Copenhageni revealed that both
      strains have complete biosynthetic pathways for legionamimic acid synthesis, a
      molecule with the same stereochemistry as sialic acid. Lectin-based affinity
      purification of NulO-modified molecules, followed by mass spectrometric
      identification suggests post-translational modification of surface lipoproteins,
      including Loa22. CONCLUSIONS: Leptospira species encode NulO biosynthetic
      pathways and synthesize multiple NulO molecules including sialic acid. Additional
      studies are needed to clarify the exact context and functional significance of
      NulO expression. These findings have implications for immune evasion during
      systemic leptospirosis.

PMID- 22853806
TI  - Characterization of the pore structure of three-dimensionally ordered mesoporous
      carbons using high resolution gas sorption.
AB  - The use of colloidal crystals with various primary particle sizes as templates
      leads to the formation of three-dimensionally ordered mesoporous (3DOm) carbons
      containing spherical pores with tailorable pore size and extremely high pore
      volumes. We present a comprehensive structural characterization of these novel
      carbons by using nitrogen (77.4 K) and argon (87.3 K) adsorption coupled with the
      application of novel, dedicated quenched solid density functional theory (QSDFT)
      methods which assume correctly the underlying spherical pore geometry and also
      the underlying adsorption mechanism. The observed adsorption isotherms are of
      Type IV with Type H1-like hysteresis, despite the fact that pore blocking affects
      the position of the desorption branch. This follows also from detailed, advanced
      scanning hysteresis experiments which not only allow one to identify the
      underlying mechanisms of hysteresis, but also provide complementary information
      about the texture of these unique porous materials. This work addresses the
      problem of pore size analysis of novel, ordered porous carbons and highlights the
      importance of hysteresis scanning experiments for textural analysis of the pore
      network.

PMID- 22853807
TI  - Evolutionary patterns of RNA-based gene duplicates in Caenorhabditis nematodes
      coincide with their genomic features.
AB  - BACKGROUND: RNA-based gene duplicates (retrocopies) played pivotal roles in many
      physiological processes. Nowadays, functional retrocopies have been
      systematically identified in several mammals, fruit flies, plants, zebrafish and
      other chordates, etc. However, studies about this kind of duplication in
      Caenorhabditis nematodes have not been reported. FINDINGS: We identified 43, 48,
      43, 9, and 42 retrocopies, of which 6, 15, 18, 3, and 13 formed chimeric genes in
      C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei, respectively.
      At least 5 chimeric types exist in Caenorhabditis species, of which retrocopy
      recruiting both N and C terminus is the commonest one. Evidences from different
      analyses demonstrate many retrocopies and almost all chimeric genes may be
      functional in these species. About half of retrocopies in each species has
      coordinates in other species, and we suggest that retrocopies in closely related
      species may be helpful in identifying retrocopies for one certain species.
      CONCLUSIONS: A number of retrocopies and chimeric genes exist in Caenorhabditis
      genomes, and some of them may be functional. The evolutionary patterns of these
      genes may correlate with their genomic features, such as the activity of
      retroelements, the high rate of mutation and deletion rate, and a large
      proportion of genes subject to trans-splicing.

PMID- 22853808
TI  - A UK and Irish survey of enteral nutrition practices in paediatric intensive care
      units.
AB  - The aim of the present study was to describe the present knowledge of healthcare
      professionals and the practices surrounding enteral feeding in the UK and Irish
      paediatric intensive care unit (PICU) and propose recommendations for practice
      and research. A cross-sectional (thirty-four item) survey was sent to all PICU
      listed in the Paediatric Intensive Care Audit Network (PICANET) database
      (http://www.picanet.org.uk) in November 2010. The overall PICU response rate was
      90 % (27/30 PICU; 108 individual responses in total). The overall breakdown of
      the professional groups was 59 % nursing staff (most were children's nurses), 27
      % medical staff, 13 % dietitians and 1 % physician assistants. Most units (96 %)
      had some written guidance (although brief and generic) on enteral nutrition (EN);
      85 % of staff, across all professional groups (P= 0.672), thought that guidelines
      helped to improve energy delivery in the PICU. Factors contributing to reduced
      energy delivery included: fluid-restrictive policies (60 %), the child just being
      'too ill' to feed (17 %), surgical post-operative orders (16 %), nursing staff
      being too slow in starting feeds (7 %), frequent procedures requiring fasting (7
      %) and haemodynamic instability (7 %). What constituted an 'acceptable' level of
      gastric residual volume (GRV) varied markedly across respondents, but GRV
      featured prominently in the decision to both stop EN and to determine feed
      tolerance and was similar for all professional groups. There was considerable
      variation across respondents about which procedures required fasting and the
      duration of this fasting. The present survey has highlighted the variability of
      the present enteral feeding practices across the UK and Ireland, particularly
      with regard to the use of GRV and fasting for procedures. The present study
      highlights a number of recommendations for both practice and research.

PMID- 22853809
TI  - Traumatic superior ophthalmic vein thrombosis in a child.
AB  - Superior ophthalmic vein thrombosis (SOVT) is a rare condition of multiple
      etiologies that generally presents with proptosis, ophthalmoplegia, periorbital
      edema, and occasionally decreased visual acuity. We describe a unique case of a
      two-year-old child presenting with extensive superior forniceal chemosis
      obstructing the visual axis after trauma in a motor vehicle accident. Angiography
      revealed complete thrombosis of the superior ophthalmic vein. Management and
      outcome are also discussed.

PMID- 22853811
TI  - Ten qualities of a good researcher.
AB  - Writing about the 10 Qualities of a Good Researcher represents a great
      responsibility since it is not simple to assemble in a concise manner all the
      important qualities of a good researcher. Knowing the difficulties lying ahead, I
      would like to suggest the following qualities: interest, motivation,
      inquisitiveness, commitment, sacrifice, excelling, knowledge, recognition,
      scholarly approach, and integration. The characterization and understanding of
      these qualities would be extremely helpful to those who are beginning the
      exciting field of research. To be a good researcher first requires the intention
      to be involved in research and immediately thereafter to show a dedicated
      interest to do the best research possible. From there we must accumulate the
      knowledge needed to advance the current ideas already existent in the research
      world. The intention of this writing is to introduce 10 qualities that I consider
      essential for a good researcher to succeed.

PMID- 22853810
TI  - A satellite-based multi-pollutant index of global air quality.

PMID- 22853812
TI  - Multivariate methods in research.
AB  - Univariate methods are very helpful when utilized appropriately within the
      research analysis. However, there are many occasions in which only multivariate
      methods will satisfy an optimal assessment. In this case, multivariate methods
      will permit the researcher to incorporate many variables within a single research
      analysis. This work reviews the use of multivariate methods and how to apply them
      in clinical medicine.

PMID- 22853814
TI  - Toll-like receptor signaling in liver ischemia and reperfusion.
AB  - Liver ischemia-reperfusion (I/R) injuries are significant clinical challenges
      implicated in various hepatic surgical procedures and transplantations.
      Associated with varying degrees of insult, the hallmark of I/R is the excessive
      inflammatory response potentiated by the host immune system. Toll-like receptors
      (TLRs), known to play an important role in pathogen-derived inflammation, are now
      thought to participate in I/R injury-derived inflammation signaling pathways.
      Endogenous particles (proteins, cytokines, nucleic acids) that are released from
      damaged host cells bind to TLR2, TLR4, and TLR9, resulting in even further injury
      by subsequent inflammatory reactions and activation of the innate immune system.
      This review aims to systematically examine the current literature about TLR
      signaling mechanisms, allowing for a greater understanding of the precise role of
      TLRs in hepatic I/R injuries.

PMID- 22853813
TI  - Effects of oriental sweet gum storax on porcine wound healing.
AB  - PURPOSE: The objective of the present study was to assess the effects of oriental
      sweet gum (Liquidambar orientalis Mill.) storax on partial-thickness and full
      thickness wounds compared to conventional wound dressings in a porcine model.
      METHODS: Six young Yorkshire pigs were used. Sixteen square excisional wounds
      measuring 3 * 3 cm were performed per animal. The wounds were allocated to one of
      the four treatment modalities: storax, hydrocolloid dressing, silver
      sulfadiazine, and control groups. Partial-thickness wounds were created in two
      pigs, and tissue samples were harvested on days 4 and 8, respectively. Full
      thickness wounds were created in four pigs, and tissue samples were taken on days
      4, 8, 14, and 21, respectively. Histologically, all wounds were examined for re
      epithelialization and granulation tissue formation. Tissue hydroxyproline content
      and wound contraction areas were measured. RESULTS: In storax-applied group,
      there was a greater depth of granulation tissue at 4 and 8 days compared to all
      other groups (p < .0125), and there was a faster re-epithelialization at 21 days
      compared to both hydrocolloid dressing and control groups in full-thickness
      wounds (p < .0125). Tissue hydroxyproline content and wound contraction did not
      differ significantly between the groups. CONCLUSION: The results of this study
      indicate that topical application of storax enhanced both re-epithelialization
      and granulation tissue formation in full-thickness wounds. Further studies are
      indicated in this important area of wound healing research to evaluate the
      clinical efficacy of this storax and search for the mechanisms that explain its
      effects.

PMID- 22853816
TI  - Addition of granulocyte macrophage colony stimulating factor does not improve
      response to early treatment of high-risk chronic lymphocytic leukemia with
      alemtuzumab and rituximab.
AB  - Thirty-three previously untreated patients with high-risk chronic lymphocytic
      leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and
      rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to
      the regimen to determine whether it would improve treatment efficacy without
      increasing toxicity. High risk was defined as at least one of the following:
      17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated
      expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 MUg
      Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10
      mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and
      intravenous rituximab (375 mg/m(2)/week) for 4 weeks from day 8. Patients
      received standard supportive care and were monitored weekly for cytomegalovirus
      (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to
      treatment, with nine (27%) complete responses (one with persistent cytopenia) and
      nine (27%) nodular partial responses. Median progression-free survival was 13.0
      months and time to next treatment was 33.5 months. No patient died during
      treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10
      (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and
      rituximab decreased treatment efficacy and increased the rate of CMV reactivation
      compared to a historical control.

PMID- 22853817
TI  - Epidemiological analysis of critically ill adult patients with pandemic influenza
      A(H1N1) in South Korea.
AB  - A total of 245 patients with confirmed 2009 H1N1 influenza were admitted to the
      intensive-care units of 28 hospitals (South Korea). Their mean age was 55.3 years
      with 68.6% aged >50 years, and 54.7% male. Nine were obese and three were
      pregnant. One or more comorbidities were present in 83.7%, and nosocomial
      acquisition occurred in 14.3%. In total, 107 (43.7%) patients received
      corticosteroids and 66.1% required mechanical ventilation. Eighty (32.7%)
      patients died within 30 days after onset of symptoms and 99 (40.4%) within 90
      days. Multivariate logistic regression analysis showed that the clinician's
      decision to prescribe corticosteroids, older age, Sequential Organ Failure
      Assessment score and nosocomial bacterial pneumonia were independent risk factors
      for 90-day mortality. In contrast with Western countries, critical illness in
      Korea in relation to 2009 H1N1 was most common in older patients with chronic
      comorbidities; nosocomial acquisition occurred occasionally but disease in obese
      or pregnant patients was uncommon.

PMID- 22853818
TI  - Pharmacokinetic profiles of artesunate following multiple intravenous doses of 2,
      4, and 8 mg/kg in healthy volunteers: phase 1b study.
AB  - BACKGROUND: Severe malaria results in over a million deaths every year, most of
      them in children aged less than five years and living in sub-Saharan Africa.
      Injectable artesunate (AS) was recommended as initial treatment for severe
      malaria by WHO in 2006. The Walter Reed Army Institute of Research (WRAIR) has
      been developing a novel good manufacturing practice (GMP) injection of AS, which
      was approved by the US FDA for investigational drug use and distribution by the
      CDC. METHODS: Tolerability and pharmacokinetics of current GMP intravenous AS, as
      an anti-malarial agent, were evaluated after ascending multiple doses of 2, 4,
      and 8 mg/kg daily for three days with 2-minute infusion in 24 healthy subjects
      (divided into three groups) in the Phase 1 clinical trial study. RESULTS: Results
      showed that there were no dose-dependent increases in any adverse events. Drug
      concentrations showed no accumulation and no decline of the drug during the three
      days of treatment. After intravenous injection, parent drug rapidly declined and
      was converted to dihydroartemisinin (DHA) with overall mean elimination half
      lives ranging 0.15-0.23 hr for AS and 1.23-1.63 hr for DHA, but the peak
      concentration (C(max)) of AS was much higher than that of DHA with a range of
      3.08-3.78-folds. In addition, the AUC and C(max) values of AS and DHA were
      increased proportionally to the AS climbing multiple doses. DISCUSSION: The
      safety of injectable AS, even at the highest dose of 8 mg/kg increases the
      probability of therapeutic success of the drug even in patients with large
      variability of parasitaemia.

PMID- 22853819
TI  - Prospective risk of intrauterine fetal death in monoamniotic twin pregnancies.
AB  - This study was conducted to review the overall short-term outcome of monoamniotic
      twins in Japan and to determine the prospective risk of fetal death so as to
      adequately counsel parents with monoamniotic twins. Study subjects were 101 women
      with monoamniotic twins who were registered with the Japan Society of Obstetrics
      and Gynecology Successive Pregnancy Birth Registry System and who had given birth
      at >=22 weeks of gestation during 2002-2009. The gestational week at delivery
      (mean+/-SD) was 31.8+/-3.7. Fourteen women experienced intrauterine fetal death
      (IUFD). Short-term outcomes of co-twins born to the 14 women included 8 IUFDs,
      one early neonatal death within 7 days of life (END), and 5 survivors. Four other
      women experienced 5 ENDs. Thus, 13.9% (28/202) of infants died perinatally (22
      IUFDs and 6 ENDs), 13.9% (14/101) of women experienced IUFD, and 82.2% (83/101)
      of women experienced neither IUFD nor END. Structural anomalies and twin-to-twin
      transfusion syndrome explained 17.9% (five infants) and 10.7% (three infants) of
      the 28 perinatal deaths, respectively. The prospective risk of IUFD was 13.9%
      (14/101) for women who reached gestational week 22(-0/7), gradually decreasing
      thereafter but remaining at between 4.5% and 8.0% between gestational week 30(
      0/7) and 36(-0/7).

PMID- 22853820
TI  - Allocation techniques for balance at baseline in cluster randomized trials: a
      methodological review.
AB  - Reviews have repeatedly noted important methodological issues in the conduct and
      reporting of cluster randomized controlled trials (C-RCTs). These reviews usually
      focus on whether the intracluster correlation was explicitly considered in the
      design and analysis of the C-RCT. However, another important aspect requiring
      special attention in C-RCTs is the risk for imbalance of covariates at baseline.
      Imbalance of important covariates at baseline decreases statistical power and
      precision of the results. Imbalance also reduces face validity and credibility of
      the trial results. The risk of imbalance is elevated in C-RCTs compared to trials
      randomizing individuals because of the difficulties in recruiting clusters and
      the nested nature of correlated patient-level data. A variety of restricted
      randomization methods have been proposed as way to minimize risk of imbalance.
      However, there is little guidance regarding how to best restrict randomization
      for any given C-RCT. The advantages and limitations of different allocation
      techniques, including stratification, matching, minimization, and covariate
      constrained randomization are reviewed as they pertain to C-RCTs to provide
      investigators with guidance for choosing the best allocation technique for their
      trial.

PMID- 22853821
TI  - Organizing pneumonia after stereotactic ablative radiotherapy of the lung.
AB  - BACKGROUND: Organizing pneumonia (OP), so called bronchiolitis obliterans
      organizing pneumonia after postoperative irradiation for breast cancer has been
      often reported. There is little information about OP after other radiation
      modalities. This cohort study investigated the clinical features and risk factors
      of OP after stereotactic ablative radiotherapy of the lung (SABR). METHODS:
      Patients undergoing SABR between 2004 and 2010 in two institutions were
      investigated. Blood test and chest computed tomography were performed at
      intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1)
      mixture of patchy and ground-glass opacity, 2) general and/or respiratory
      symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume
      receiving < 0.5 Gy, and 4) no evidence of a specific cause. RESULTS: Among 189
      patients (164 with stage I lung cancer and 25 with single lung metastasis)
      analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence
      interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These
      symptoms and pulmonary infiltration rapidly improved after corticosteroid
      therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP)
      around the tumor 2 to 7 months before OP. The prior RP history was strongly
      associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis.
      CONCLUSIONS: This is the first report on OP after SABR. The incidence appeared to
      be relatively high. The symptoms were sometimes severe, but corticosteroid
      therapy was effective. When patients after SABR present with unusual pneumonia,
      OP should be considered as a differential diagnosis, especially in patients with
      prior symptomatic RP.

PMID- 22853822
TI  - Short-term intermittent hypoxia reduces the severity of acute mountain sickness.
AB  - Intermittent hypoxia (IH) is a promising approach to induce acclimatization and
      hence lower the risk of developing acute mountain sickness (AMS). We hypothesized
      that a short-term IH protocol in normobaric hypoxia (7 * 1 h to 4500 m)
      effectively increases the hypoxic ventilatory response (HVR) and reduces the
      incidence and severity of AMS. Therefore, 26 men (25.5 +/- 4.4 years), assigned
      in a double-blinded fashion to the hypoxia group (HG) or placebo group (PG),
      spent 8 h at 5300 m before (PRE) and 2 days after cessation of the IH protocol
      (POST). Measurements included the evaluation of the Lake Louise Score (LLS) and
      the HVR. The severity of AMS decreased from PRE to POST in the HG (from 6.0 +/-
      2.7 at PRE to 4.1 +/- 2.1 at POST), whereas the LLS in the PG stayed high (from
      5.7 +/- 2.9 to 5.5 +/- 2.8, respectively). The HVR in the HG increased from 0.73
      +/- 0.4 L/min/% at PRE to 1.10 +/- 0.5 L/min/% at POST and did not increase in
      the PG. The reduction of the LLS was inversely related to the changes in the HVR
      (r = -0.434), but the AMS incidence was not different between the HG and the PG
      at POST. In conclusion, short-term IH reduced the severity of AMS development
      during a subsequent 8-h exposure to normobaric hypoxia.

PMID- 22853823
TI  - Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma
      and neuroblastoma cells.
AB  - BACKGROUND: Enterovirus 71 (EV71) is a major causative agent of hand-foot-and
      mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may
      result in a high mortality in children less than 2 years old. Although there are
      two highly glycosylated membrane proteins, SCARB2 and PSGL-1, which have been
      identified as the cellular and functional receptors of EV71, the role of
      glycosylation in EV71 infection is still unclear. RESULTS: We demonstrated that
      the attachment of EV71 to RD and SK-N-SH cells was diminished after the removal
      of cell surface sialic acids by neuraminidase. Sialic acid specific lectins,
      Maackia amurensis (MAA) and Sambucus Nigra (SNA), could compete with EV71 and
      restrained the binding of EV71 significantly. Preincubation of RD cells with
      fetuin also reduced the binding of EV71. In addition, we found that SCARB2 was a
      sialylated glycoprotein and interaction between SCARB2 and EV71 was retarded
      after desialylation. CONCLUSIONS: In this study, we demonstrated that cell
      surface sialic acids assist in the attachment of EV71 to host cells. Cell surface
      sialylation should be a key regulator that facilitates the binding and infection
      of EV71 to RD and SK-N-SH cells.

PMID- 22853825
TI  - Density functional theoretical investigation of remarkably high selectivity of
      the Cs+ ion over the Na+ ion toward macrocyclic hybrid calix-bis-crown ether.
AB  - Density functional theoretical analysis was performed to explore the enhanced
      selectivity of the Cs(+) ion over the Na(+) ion with hybrid calix[4]-bis-crown
      macrocyclic ligand compared to 18-crown-6 ether. The calculated selectivity data
      for Cs(+)/Na(+) with hybrid calix[4]-bis-crown ligand using the free energy of
      extraction employing thermodynamical cycle was found to be in excellent agreement
      with the reported solvent extraction results. The present study further
      establishes that the selectivity for a specific metal ion between two competitive
      ligands is primarily due to the complexation free energy of the ligand to the
      metal ions and is independent of the aqueous solvent effect but strongly depends
      on the dielectricity of the organic solvents and the presence of the coanion.

PMID- 22853824
TI  - Understanding how adherence goals promote adherence behaviours: a repeated
      measure observational study with HIV seropositive patients.
AB  - BACKGROUND: The extent to which patients follow treatments as prescribed is
      pivotal to treatment success. An exceptionally high level (> 95%) of HIV
      medication adherence is required to suppress viral replication and protect the
      immune system and a similarly high level (> 80%) of adherence has also been
      suggested in order to benefit from prescribed exercise programmes. However, in
      clinical practice, adherence to both often falls below the desirable level. This
      project aims to investigate a wide range of psychological and personality factors
      that may lead to adherence/non-adherence to medical treatment and exercise
      programmes. METHODS: HIV positive patients who are referred to the
      physiotherapist-led 10-week exercise programme as part of the standard care are
      continuously recruited. Data on social cognitive variables (attitude, intention,
      subjective norms, self-efficacy, and outcome beliefs) about the goal and specific
      behaviours, selected personality factors, perceived quality of life, physical
      activity, self-reported adherence and physical assessment are collected at
      baseline, at the end of the exercise programme and again 3 months later. The
      project incorporates objective measures of both exercise (attendance log and
      improvement in physical measures such as improved fitness level, weight loss,
      improved circumferential anthropometric measures) and medication adherence
      (verified by non-invasive hair analysis). DISCUSSION: The novelty of this project
      comes from two key aspects, complemented with objective information on exercise
      and medication adherence. The project assesses beliefs about both the underlying
      goal such as following prescribed treatment; and about the specific behaviours
      such as undertaking the exercise or taking the medication, using both implicit
      and explicit assessments of patients' beliefs and attitudes. We predict that i)
      the way people think about the underlying goal of their treatments explains
      medication and exercise behaviours over and above the effects of the behaviour
      specific thinking and ii) the relationship between adherence to exercise and to
      medical treatment is stronger among those with more favourable views about the
      goal. Results from this study should identify the key contributing factors to
      inform subsequent adherence research and afford a more streamlined assessment
      matrix. The project also aims to inform patient care practices. UK CLINICAL
      RESEARCH NETWORK REGISTRATION NUMBER: UKCRN 7842.

PMID- 22853826
TI  - Is there a role of whole-body bone scan in patients with esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Correct detection of bone metastases in patients with esophageal
      squamous cell carcinoma is pivotal for prognosis and selection of an appropriate
      treatment regimen. Whole-body bone scan for staging is not routinely recommended
      in patients with esophageal squamous cell carcinoma. The aim of this study was to
      investigate the role of bone scan in detecting bone metastases in patients with
      esophageal squamous cell carcinoma. METHODS: We retrospectively evaluated the
      radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma
      patients between 1999 and 2008. Of these 360 patients, 288 patients received bone
      scan during pretreatment staging, and sensitivity, specificity, positive
      predictive value, and negative predictive value of bone scan were determined. Of
      these 360 patients, surgery was performed in 161 patients including 119 patients
      with preoperative bone scan and 42 patients without preoperative bone scan. Among
      these 161 patients receiving surgery, 133 patients had stages II + III disease,
      including 99 patients with preoperative bone scan and 34 patients without
      preoperative bone scan. Bone recurrence-free survival and overall survival were
      compared in all 161 patients and 133 stages II + III patients, respectively.
      RESULTS: The diagnostic performance for bone metastasis was as follows:
      sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and
      negative predictive value, 97.9%. In all 161 patients receiving surgery, absence
      of preoperative bone scan was significantly associated with inferior bone
      recurrence-free survival (P = 0.009, univariately). In multivariate comparison,
      absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the
      independent adverse prognosticator for bone recurrence-free survival. In 133
      stages II + III patients receiving surgery, absence of preoperative bone scan was
      significantly associated with inferior bone recurrence-free survival (P = 0.003,
      univariately) and overall survival (P = 0.037, univariately). In multivariate
      comparison, absence of preoperative bone scan was independently associated with
      inferior bone recurrence-free survival (P = 0.009, odds ratio: 5.832) and overall
      survival (P = 0.029, odds ratio: 1.603). CONCLUSIONS: Absence of preoperative
      bone scan was significantly associated with inferior bone recurrence-free
      survival, suggesting that whole-body bone scan should be performed before
      esophagectomy in patients with esophageal squamous cell carcinoma, especially in
      patients with advanced stages.

PMID- 22853827
TI  - Knowledge of skull base anatomy and surgical implications of human sacrifice
      among pre-Columbian Mesoamerican cultures.
AB  - Human sacrifice became a common cultural trait during the advanced phases of
      Mesoamerican civilizations. This phenomenon, influenced by complex religious
      beliefs, included several practices such as decapitation, cranial deformation,
      and the use of human cranial bones for skull mask manufacturing. Archaeological
      evidence suggests that all of these practices required specialized knowledge of
      skull base and upper cervical anatomy. The authors conducted a systematic search
      for information on skull base anatomical and surgical knowledge among
      Mesoamerican civilizations. A detailed exposition of these results is presented,
      along with some interesting information extracted from historical documents and
      pictorial codices to provide a better understanding of skull base surgical
      practices among these cultures. Paleoforensic evidence from the Great Temple of
      Tenochtitlan indicates that Aztec priests used a specialized decapitation
      technique, based on a deep anatomical knowledge. Trophy skulls were submitted
      through a stepwise technique for skull mask fabrication, based on skull base
      anatomical landmarks. Understanding pre-Columbian Mesoamerican religions can only
      be realized by considering them in their own time and according to their own
      perspective. Several contributions to medical practice might have arisen from
      anatomical knowledge emerging from human sacrifice and decapitation techniques.

PMID- 22853828
TI  - Petrosal approaches to brainstem cavernous malformations.
AB  - OBJECT: Although they provide excellent ventral and lateral exposure of the
      brainstem, petrosal approaches to brainstem cavernous malformations (CMs) are
      infrequently reported. METHODS: The authors reviewed their experience with
      petrosal approaches to brainstem CMs in combination with a comprehensive review
      of the literature to elucidate resection rates, complication rates, and outcomes.
      RESULTS: Including their own results, the authors found 65 cases in 20 reports of
      brainstem CMs treated with petrosal approaches. The specific approaches were
      posterior petrosal in 37 cases (57%), anterior petrosal in 17 (26%), extended
      posterior petrosal in 10 (15%), and a combined petrosal approach in 1 case (2%).
      For 50 cases in 16 reports with detailed outcome information, the overall
      complete resection rate was 90%, with early postoperative morbidity reported in
      30% of cases and permanent morbidity in 14%. The rate of CSF leakage was 6%.
      CONCLUSIONS: The versatile petrosal approaches to brainstem CMs are associated
      with good outcomes and an acceptable morbidity rate. More expansive lesions can
      be approached using a combination of the standard anterior and posterior petrosal
      approach, preserving hearing and avoiding the greater complication rates
      associated with extended posterior petrosal approaches.

PMID- 22853829
TI  - A lesson in history: the evolution of endoscopic third ventriculostomy.
AB  - The history of endoscopic third ventriculostomy (ETV) demonstrates the importance
      of studying neurosurgery's history. A story that began with numerous
      technological advancements started to fizzle as neurosurgeons were stymied by
      problems encountered during the infancy of the technology they were still
      developing. The new technique, although sound in theory, failed to deliver a
      realistic solution for managing hydrocephalus; it lost the battle to the valved
      shunt. Over the last 15-20 years, a clearer understanding of pathophysiological
      mechanisms underlying various forms of hydrocephalus, along with effective
      implementation of evidence-based practice, has allowed for optimization of
      patient selection and a remarkable improvement in ETV success rates.
      Neurosurgeons would be wise to take the lessons learned in modernizing the ETV
      procedure and reassure themselves that these lessons do not apply to other
      methods that are tempting to dismiss as antiquated or archaic.

PMID- 22853830
TI  - Dr. Otto "Tiger" Freer: inventor and innovator.
AB  - Every neurosurgeon develops his or her own standard approach to common
      intracranial pathologies in terms of the order in which different stages are
      performed and which instruments are used to perform individual tasks. The
      majority of the basic steps in performing a craniotomy are learned through
      repetition and practice during residency training. Significant amounts of energy
      are devoted to mastering technical skills and developing an operative rhythm.
      What often receives little attention is the historical origin of the instruments
      that make the work possible. The Freer elevator represents a particularly
      interesting example. To people unfamiliar with the accomplishments of turn-of-the
      century laryngologist Otto "Tiger" Freer, it can be assumed that the name of the
      instrument in one's hand is simply named for what it can do, that is, to "free"
      the nasal mucosa from the bony and cartilaginous septum during the
      transsphenoidal approach. The technique this master surgeon spent his life and
      career perfecting is now repeated almost daily by skull base neurosurgeons
      approaching pathologies from the inferior frontal lobe to the foramen magnum. In
      reviewing his life and work, the authors of this paper discovered an interesting
      creative process that led to the design of the eponymous instrument.
      Additionally, they discovered important advances toward the development of the
      transnasal approach and in our understanding of the anterior skull base. They
      present a historical perspective on the life and accomplishments of Dr. Freer and
      the ubiquitous surgical instrument that he invented and popularized.

PMID- 22853831
TI  - Jugulotympanic paragangliomas: 75 years of evolution in understanding.
AB  - Jugulotympanic paragangliomas were first described approximately 75 years ago.
      Since that time, there has been considerable evolution in knowledge of tumor
      biology, methods of classification, and appropriate management strategies. This
      paper attempts to summarize these gains in information.

PMID- 22853832
TI  - Current intraoperative devices to reduce visual loss after spine surgery.
AB  - Postoperative visual loss (POVL) after spine surgery performed with the patient
      prone is a rare but devastating postoperative complication. The incidence and the
      mechanisms of visual loss after surgery are difficult to determine. The 4
      recognized causes of POVL are ischemic optic neuropathy (approximately 89%),
      central retinal artery occlusion (approximately 11%), cortical infarction, and
      external ocular injury. There are very limited guidelines or protocols on the
      perioperative practice for "prone-position" surgeries. However, new devices have
      been designed to prevent mechanical ocular compression during prone-position
      spine surgeries. The authors used PubMed to perform a literature search for
      devices used in prone-position spine surgeries. A total of 7 devices was found;
      the authors explored these devices' features, advantages, and disadvantages. The
      cause of POVL seems to be a multifactorial problem with unclear
      pathophysiological mechanisms. Therefore, ocular compression is a critical
      factor, and eliminating any obvious compression to the eye with these devices
      could possibly prevent this devastating perioperative complication.

PMID- 22853833
TI  - The journey of discovering skull base anatomy in ancient Egypt and the special
      influence of Alexandria.
AB  - The field of anatomy, one of the most ancient sciences, first evolved in Egypt.
      From the Early Dynastic Period (3100 BC) until the time of Galen at the end of
      the 2nd century ad, Egypt was the center of anatomical knowledge, including
      neuroanatomy. Knowledge of neuroanatomy first became important so that sacred
      rituals could be performed by ancient Egyptian embalmers during mummification
      procedures. Later, neuroanatomy became a science to be studied by wise men at the
      ancient temple of Memphis. As religious conflicts developed, the study of the
      human body became restricted. Myths started to replace scientific research,
      squelching further exploration of the human body until Alexander the Great
      founded the city of Alexandria. This period witnessed a revolution in the study
      of anatomy and functional anatomy. Herophilus of Chalcedon, Erasistratus of
      Chios, Rufus of Ephesus, and Galen of Pergamon were prominent physicians who
      studied at the medical school of Alexandria and contributed greatly to knowledge
      about the anatomy of the skull base. After the Royal Library of Alexandria was
      burned and laws were passed prohibiting human dissections based on religious and
      cultural factors, knowledge of human skull base anatomy plateaued for almost 1500
      years. In this article the authors consider the beginning of this journey, from
      the earliest descriptions of skull base anatomy to the establishment of basic
      skull base anatomy in ancient Egypt.

PMID- 22853834
TI  - Humphrey Ridley (1653-1708): 17th century evolution in neuroanatomy and selective
      cerebrovascular injections for cadaver dissection.
AB  - Humphrey Ridley, M.D. (1653-1708), is a relatively unknown historical figure,
      belonging to the postmedieval era of neuroanatomical discovery. He was born in
      the market town of Mansfield, 14 miles from the county of Nottinghamshire,
      England. After studying at Merton College, Oxford, he pursued medicine at Leiden
      University in the Netherlands. In 1688, he was incorporated as an M.D. at
      Cambridge. Ridley authored the first original treatise in English language on
      neuroanatomy, The Anatomy of the Brain Containing its Mechanisms and Physiology:
      Together with Some New Discoveries and Corrections of Ancient and Modern Authors
      upon that Subject.   Ridley described the venous anatomy of the eponymous
      circular sinus in connection with the parasellar compartment. His methods were
      novel, unique, and effective. To appreciate the venous anatomy, he preferred to
      perform his anatomical dissections on recently executed criminals who had been
      hanged. These cadavers had considerable venous engorgement, which made the skull
      base venous anatomy clearer. To enhance the appearance of the cerebral
      vasculature further, he used tinged wax and quicksilver in the injections. He set
      up experimental models to answer questions definitively, in proving that the
      arachnoid mater is a separate meningeal layer. The first description of the
      subarachnoid cisterns, blood-brain barrier, and the fifth cranial nerve ganglion
      with its branches are also attributed to Ridley.   This historical vignette
      revisits Ridley's life and academic work that influenced neuroscience and
      neurosurgical understanding in its infancy. It is unfortunate that most of his
      novel contributions have gone unnoticed and uncited. The authors hope that this
      article will inform the neurosurgical community of Ridley's contributions to the
      field of neurosurgery.

PMID- 22853835
TI  - Fedor Krause: the first systematic use of X-rays in neurosurgery.
AB  - Within a few months of Wilhelm Conrad Rontgen's discovery of x-rays in 1895,
      Fedor Krause acquired an x-ray apparatus and began to use it in his daily
      interactions with patients and for diagnosis. He was the first neurosurgeon to
      use x-rays methodically and systematically. In 1908 Krause published the first
      volume of text on neurosurgery, Chirurgie des Gehirns und Ruckenmarks (Surgery of
      the Brain and Spinal Cord), which was translated into English in 1909. The second
      volume followed in 1911. This was the first published multivolume text totally
      devoted to neurosurgery. Although Krause excelled in and promoted neurosurgery,
      he believed that surgeons should excel at general surgery. Importantly, Krause
      was inclined to adopt technology that he believed could be helpful in surgery.
      His 1908 text was the first neurosurgical text to contain a specific chapter on x
      rays ("Radiographie") that showed roentgenograms of neurosurgical procedures and
      pathology. After the revolutionary discovery of x-rays by Rontgen, many prominent
      neurosurgeons seemed pessimistic about the use of x-rays for anything more than
      trauma or fractures. Krause immediately seized on its use to guide and monitor
      ventricular drainage and especially for the diagnosis of tumors of the skull
      base. The x-ray images contained in Krause's "Radiographie" chapter provide a
      seminal view into the adoption of new technology and the development of
      neurosurgical technique and are part of neurosurgery's heritage.

PMID- 22853836
TI  - Hermann Schloffer and the origin of transsphenoidal pituitary surgery.
AB  - A little over a century ago, in 1907, at the University of Innsbruck, Hermann
      Schloffer performed the first transsphenoidal surgery on a living patient
      harboring a pituitary adenoma. Schloffer used a superior nasal route via a
      transfacial lateral rhinotomy incision. This was perhaps his greatest academic
      contribution to neurosurgery. Despite the technological limitations of that time,
      Schloffer's operation was groundbreaking in that it laid the foundation for
      future development and refinement of transsphenoidal pituitary surgery,
      influencing prominent surgeons such as Oskar Hirsch and Harvey Cushing. Even
      after undergoing multiple modifications and a brief fall into obscurity, the
      transsphenoidal approach has endured through generations of surgeons and remains
      the preferred approach for lesions of the sella turcica to this day. Although
      Schloffer performed primarily abdominal surgery in his practice, his
      contributions to the transsphenoidal approach have had a lasting impact in the
      field of pituitary and skull base surgery. The authors review the life and career
      of Hermann Schloffer, the surgical details of his transsphenoidal operation, and
      the legacy that it has left on the field of pituitary surgery.

PMID- 22853837
TI  - Norman Dott, Gerard Guiot, and Jules Hardy: key players in the resurrection and
      preservation of transsphenoidal surgery.
AB  - Developed over a century ago, the transsphenoidal approach to access lesions of
      the pituitary gland and sella turcica has transformed the field of neurosurgery,
      largely due to the work of Oskar Hirsch and Harvey Cushing. Furthermore, its use
      and modification in the early 1900s was perhaps one of Cushing's greatest
      legacies to skull base surgery. However, Cushing, who had worked relentlessly to
      improve the transsphenoidal route to the pituitary region, abandoned the approach
      by 1929 in his pursuit to master transcranial approaches to the suprasellar
      region. Hirsch and a few other surgeons continued to perform transsphenoidal
      operations, but they were unable to maintain the popularity of the approach among
      their peers. During a time when transsphenoidal surgery was on the brink of
      extinction, a critical lineage of 3 key surgeons--Norman Dott, Gerard Guiot, and
      Jules Hardy--would resurrect the art, each working to further improve the
      procedure. Dott, Cushing's apprentice from 1923 to 1924, brought his experiences
      with transsphenoidal surgery to Edinburgh, Scotland, and along the way, developed
      the lighted nasal speculum to provide better illumination in the narrow working
      area. Guiot, inspired by Dott, adopted his technique and used intraoperative
      radiofluoroscopic technique for image guidance. Hardy, a fellow of Guiot, from
      Montreal, Canada, revolutionized transsphenoidal microsurgery with the
      introduction of the binocular microscope and selective adenomectomy. The
      teachings of these pioneers have endured over time and are now widely used by
      neurosurgeons worldwide. In this paper, we review the lineage and contributions
      of Dott, Guiot, and Hardy who served as crucial players in the preservation of
      transsphenoidal surgery.

PMID- 22853838
TI  - Evolution of the posterior petrosal approach.
AB  - In this article, the authors review the history of the posterior petrosal
      approach. The early foundation of the retrolabyrinthine lateral petrosectomy has
      its roots in the otolaryngology literature. These early approaches were limited
      in exposure by the tentorium superiorly and the sigmoid sinus posteriorly.
      Although the concept of a transtentorial approach was originally combined with a
      complete labyrinthectomy, Hakuba and colleagues described the expansive exposure
      afforded by sectioning the tentorium and superior petrosal sinus and mobilizing a
      skeletonized sigmoid sinus. This maneuver serves as the key step in allowing for
      the full, combined supra- and infratentorial exposure that the posterior petrosal
      approach provides. In contrast to Hakuba et al.'s approach, which used a partial
      labyrinthectomy, modern approaches often preserve the entire labyrinth
      (retrolabyrinthine approach). For added exposure, the latter can be combined with
      the anterior petrosal approach, allowing for the preservation of hearing and an
      enhanced view of the surgical target. The authors review the evolution of the
      petrosal approach and highlight its applicability.

PMID- 22853839
TI  - The history of the combined supra- and infratentorial approach to the petroclival
      region.
AB  - Lesions of the ventrolateral brainstem, clivus, and cerebellopontine angle pose
      significant challenges for surgeons, and the rate of morbidity and mortality from
      classic neurosurgical approaches has proven to be unacceptably high. Early
      attempts to expose this region consisted primarily of an extended suboccipital
      craniectomy, with opening of the tentorium and ligation of the sigmoid sinus for
      additional exposure. During the 1960s, technological innovations including the
      surgical microscope and the pneumatic drill allowed surgeons to gain additional
      exposure by removing more bone from the base of the skull. This let surgeons
      define combined infra- and supratentorial approaches, which rely less on brain
      retraction to resect these difficult tumors successfully. These approaches rely
      on a combined posterior mastoid approach with an anterior petrosectomy. The
      evolution of this approach is discussed in this paper.

PMID- 22853840
TI  - Petrosal approaches to posterior circulation aneurysms.
AB  - Complex posterior circulation aneurysms are formidable lesions with an abysmal
      natural history. Their management continues to present a challenge to both
      endovascular and open microsurgical approaches. Affording an expansive, combined
      supra- and infratentorial exposure, the petrosal approaches are well suited for
      these challenging lesions when located along the basilar trunk or at a low-lying
      basilar apex. This report evaluates the evolution and application of petrosal
      approaches to these lesions. Excluding transsigmoid, infratentorial, or labyrinth
      sacrificing approaches, the authors found 23 reports with 61 posterior
      circulation aneurysms treated via a petrosal approach. Although early morbidity
      was not negligible, rates of aneurysm occlusion (95% overall) and long-term
      outcome were quite laudable in light of the challenge posed by these lesions.
      Moreover, with accumulating experience with petrosal approaches, rates of
      complications are likely to wane, as neurosurgeons capitalize on the expansive
      exposure afforded by these indispensable approaches.

PMID- 22853841
TI  - The history of skull base surgery.

PMID- 22853842
TI  - Metal ion controlled self-assembly of a chemically reengineered protein drug
      studied by small-angle X-ray scattering.
AB  - Precise control of the oligomeric state of proteins is of central importance for
      biological function and for the properties of biopharmaceutical drugs. Here, the
      self-assembly of 2,2'-bipyridine conjugated monomeric insulin analogues, induced
      through coordination to divalent metal ions, was studied. This protein drug
      system was designed to form non-native homo-oligomers through selective
      coordination of two divalent metal ions, Fe(II) and Zn(II), respectively. The
      insulin type chosen for this study is a variant designed for a reduced tendency
      toward native dimer formation at physiological concentrations. A small-angle X
      ray scattering analysis of the bipyridine-modified insulin system confirmed an
      organization into a novel well-ordered structure based on insulin trimers, as
      induced by the addition of Fe(II). In contrast, unmodified monomeric insulin
      formed larger and more randomly structured assemblies upon addition of Fe(II).
      The addition of Zn(II), on the other hand, led to the formation of small
      quantities of insulin hexamers for both the bipyridine-modified and the
      unmodified monomeric insulin. Interestingly, the location of the bipyridine
      modification significantly affects the tendency to hexamer formation as compared
      to the unmodified insulin. Our study shows how combining a structural study and
      chemical design can be used to obtain molecular understanding and control of the
      self-assembly of a protein drug. This knowledge may eventually be employed to
      develop an optimized in vivo drug release profile.

PMID- 22853844
TI  - Preaponeurotic fat advancement for prevention of unexpected higher eyelid crease
      in upper eyelid-lengthening surgery.
AB  - PURPOSE: To present a modified technique based on preaponeurotic fat advancement
      for preventing higher eyelid crease in upper eyelid-lengthening surgery. METHODS:
      Outcomes of Japanese patients with Graves' orbitopathy-related upper eyelid
      retraction who underwent transcutaneous upper eyelid-lengthening surgery were
      reviewed. The minimum follow-up period was 6 months. A total of 17 upper eyelids
      in 11 patients (average age, 38.4 years) were included. After confirming
      appropriate upper eyelid lowering with good contour, preaponeurotic fat was fully
      exposed and fixed on the upper tarsal plate 1 mm superior to the planned eyelid
      crease with 5 sutures. Skin-tarsus-skin sutures were placed to create an eyelid
      crease and close the skin. Simple suture tarsorrhaphy was performed with 2
      sutures. RESULTS: No upper eyelids demonstrated higher eyelid crease
      postsurgically. Upper eyelid fullness caused by the advanced preaponeurotic fat
      was not conspicuous. CONCLUSIONS: Our technique is a countermeasure against
      higher eyelid crease in upper eyelid-lengthening surgery.

PMID- 22853845
TI  - Cerebral oxygenation following epinephrine infusion.
AB  - Evidence suggests that the autonomic nervous system may actively regulate the
      cerebral vasculature. In this study, central hemodynamics and brain oxy
      hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO2Hb, bdHb and bTHb)
      were monitored during infusion of epinephrine (0.06 MUg/kg/min over 6 min, and
      0.12 MUg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial
      pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR),
      stroke volume (SV) and cardiac output (CO) increased, but did not affect bO2Hb,
      bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in
      both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0+/-4.6
      and +4.9+/-4.8 MUmol/L respectively, P<0.05) and persisted for 20 min post
      infusion (+1.5+/-2.2 and +1.8+/-2.7 MUmol/L respectively, P<0.05). No evidence
      was found for reduction in cerebral oxygenation during a cold-pressor test. The
      results of the present study demonstrated that clinical doses of epinephrine
      result in a delayed increase in cortical blood volume due to an increase in Oxy
      Hb, consistent with vasodilation.

PMID- 22853846
TI  - Toll-like receptor-9 agonists increase cyclin D1 expression partly through
      activation of activator protein-1 in human oral squamous cell carcinoma cells.
AB  - Increasing evidence suggests that malignant transformation can result from
      chronic infection, and Toll-like receptors (TLRs) may play an important role in
      this process. We have previously reported that the increased expression of TLR-9
      is associated with tumor cell proliferation in oral cancer. However, the
      mechanisms involved have not been elucidated. The aim of this study was to
      investigate whether CpG-oligodeoxynucleotides (CpG-ODN), a special TLR-9 agonist,
      is able to exert the proliferation-promoting effect in human oral squamous cell
      carcinoma (OSCC), and to explore the possible underlying molecular mechanism.
      Flow cytometry, MTT, and colony formation assay were used to evaluate cell
      proliferation and cell cycle distribution. The mRNA and protein levels were
      analyzed by quantitative RT-PCR and Western blot assay. Luciferase reporter gene,
      EMSA, and ChIP assays were used to detect the activity of activator protein-1 (AP
      1) and nuclear factor-kappaB (NF-kappaB) in HB cells. Results showed that CpG-ODN
      could stimulate proliferation of HB cells in a dose- and time-dependent manner
      with a promoted G(1) /S cell cycle progression. Increased cyclin D1 expression
      was detected in the nuclear region after CpG-ODN treatment. Moreover, CpG-ODN
      promoted nuclear translocation and activation of AP-1, which appeared to be
      required for TLR-9-mediated cyclin D1 expression and subsequently cell
      proliferation, but seemed to have little impact on NF-kappaB activity. Our
      results indicate that CpG-ODN stimulates tumor cell proliferation through TLR-9
      mediated AP-1-activated cyclin D1 expression in OSCC HB cells. Pharmacologic
      inhibition of the TLR-9/AP-1/cyclin D1 pathway may be a new therapeutic approach
      for prevention as well as treatment of OSCC.

PMID- 22853843
TI  - Redefining the impact of nutrition on breast cancer incidence: is epigenetics
      involved?
AB  - Breast cancer incidence is rising worldwide with an increase in aggressive
      neoplasias in young women. Possible factors involved include lifestyle changes,
      notably diet that is known to make an impact on gene transcription. However,
      among dietary factors, there is sufficient support for only greater body weight
      and alcohol consumption whereas numerous studies revealing an impact of specific
      diets and nutrients on breast cancer risk show conflicting results. Also, little
      information is available from middle- and low-income countries. The diversity of
      gene expression profiles found in breast cancers indicates that transcription
      control is critical for the outcome of the disease. This suggests the need for
      studies on nutrients that affect epigenetic mechanisms of transcription, such as
      DNA methylation and post-translational modifications of histones. In the present
      review, a new examination of the relationship between diet and breast cancer
      based on transcription control is proposed in light of epidemiological, animal
      and clinical studies. The mechanisms underlying the impact of diets on breast
      cancer development and factors that impede reaching clear conclusions are
      discussed. Understanding the interaction between nutrition and epigenetics (gene
      expression control via chromatin structure) is critical in light of the influence
      of diet during early stages of mammary gland development on breast cancer risk,
      suggesting a persistent effect on gene expression as shown by the influence of
      certain nutrients on DNA methylation. Successful development of breast cancer
      prevention strategies will require appropriate models, identification of
      biological markers for rapid assessment of preventive interventions, and
      coordinated worldwide research to discern the effects of diet.

PMID- 22853849
TI  - The relation between order of acquisition, segmental frequency and function: the
      case of word-initial consonants in Dutch.
AB  - The impact of input frequency (IF) and functional load (FL) of segments in the
      ambient language on the acquisition order of word-initial consonants is
      investigated. Several definitions of IF/FL are compared and implemented. The
      impact of IF/FL and their components are computed using a longitudinal corpus of
      interactions between thirty Dutch-speaking children (age range: 0 ; 6-2 ; 0) and
      their primary caretaker(s). The corpus study reveals significant correlations
      between IF/FL and acquisition order. The highest predictive values are found for
      the token frequency of segments, and for FL computed on minimally different word
      types in child-directed speech. Although IF and FL significantly correlate, they
      do have a different impact on the order of acquisition of word-initial
      consonants. When the impact of IF is partialed out, FL still has a significant
      correlation with acquisition order. The reverse is not true, suggesting that the
      acquisition of word-initial consonants is mainly influenced by their
      discriminating function.

PMID- 22853848
TI  - I-COMBINE study: assessment of efficacy and safety profile of
      irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine
      monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg
      monotherapy: a multicenter, phase III, prospective, randomized, open-label with
      blinded-end point evaluation study.
AB  - BACKGROUND: Hypertension guidelines recommend the use of 2 agents with
      synergistic action when >1 agent is needed to achieve blood pressure goals. Newer
      antihypertensive treatment combinations include fixed-dose combinations of an
      angiotensin receptor blocker and a calcium channel blocker. OBJECTIVE: The I
      COMBINE study aimed to determine whether the antihypertensive efficacy of the
      fixed-dose combination irbesartan 150 mg/amlodipine 5 mg (I150/A5) was superior
      to that of amlodipine 5 mg (A5) monotherapy in lowering home systolic blood
      pressure (HSBP) after 5 weeks' treatment. METHODS: The I-COMBINE study was a 10
      week, multicenter, Phase III, prospective, randomized, parallel-group, open-label
      with blinded-endpoint study. The main inclusion criterion was essential
      uncontrolled hypertension (SBP >=145 mm Hg at office, after at least 4 weeks of
      A5 monotherapy administered once daily). Patients continued to receive A5 for 7
      to 10 days and were randomized to either monotherapy with A5 for 5 weeks then
      amlodipine 10 mg (A10) for the next 5 weeks or to a fixed-dose combination
      therapy (I150/A5 then I150/A10). Safety profile was assessed by recording adverse
      events reported by patients or observed by the investigator. RESULTS: Following
      enrollment, 290 patients were randomized to treatment, and 287 (mean [SD] age,
      57.3 [11.2] years; 48% male) were included in the intention-to-treat analysis:
      144 patients treated with I150/A5 then I150/A10, and 143 patients treated with A5
      then A10. At randomization, mean HSBP was similar in both groups: 148.5 (10.3) mm
      Hg in the I150/A5 group and 149.2 (9.7) mm Hg in the A5 group. At week 5, the
      adjusted mean difference in HSBP between groups was -6.2 (1.0) mm Hg (P < 0.001).
      The proportion of controlled patients (mean home blood pressure <135 and 85 mm
      Hg) was significantly higher in the I150/A5 group than in the A5 group (P <
      0.001). Treatment-emergent adverse events were experienced by 13.8% of I150/A5
      treated patients and 11.9% of A5-treated patients during the first 5-week period,
      and by 15.8% of I150/A10-treated patients and 17.0% of A10-treated patients
      during the second 5-week period. Two serious adverse events were reported with
      the fixed-dose combination; both patients recovered. CONCLUSIONS: Data from this
      adult population with essential hypertension suggest greater efficacy with the
      fixed-dose combination I150/A5 over A5 monotherapy in lowering SBP after 5 weeks.
      Both treatment regimens were well tolerated throughout the study.
      ClinicalTrials.gov identifier: NCT00956644.

PMID- 22853850
TI  - Soot aging from OH-initiated oxidation of toluene.
AB  - We have conducted laboratory experiments to investigate the impacts of secondary
      organic aerosol formation on soot properties from OH-initiated oxidation of
      toluene. Monodisperse soot particles are exposed to the oxidation products of the
      OH-toluene reaction in an environmental chamber, and variations in particle size,
      mass, organic mass faction, morphology, effective density, hygroscopicity, and
      optical properties are simultaneously determined by an integrated aerosol
      analytical system. The thickness of the organic coating, correlated to reaction
      time and initial reactant concentrations, is shown to largely govern the particle
      properties. With the development of organic coating, the soot core is changed
      from a highly fractal to compact form, evident from the measured effective
      density and dynamic shape factor. The organic coating increases the particle
      hygroscopicity, and further exposure of coated soot to elevated relative humidity
      results in a more spherical particle. The single scattering albedo and scattering
      and absorption cross sections are also enhanced with the organic coating. Our
      results suggest that the oxidation products of anthropogenic pollutants alter the
      composition and properties of soot particles and lead to increased particle
      density, hygroscopicity, and optical properties, considerably enhancing their
      impacts on air quality, climate forcing, and human health.

PMID- 22853847
TI  - I-ADD study: assessment of efficacy and safety profile of irbesartan/amlodipine
      fixed-dose combination therapy compared with irbesartan monotherapy in
      hypertensive patients uncontrolled with irbesartan 150 mg monotherapy: a
      multicenter, phase III, prospective, randomized, open-label with blinded-end
      point evaluation study.
AB  - BACKGROUND: Hypertension guidelines recommend the use of 2 agents with
      synergistic action when >1 agent is needed to achieve blood pressure goals. Newer
      antihypertensive treatment combinations include fixed-dose combinations of an
      angiotensin receptor blocker and a calcium channel blocker. OBJECTIVE: The I-ADD
      study aimed to demonstrate whether the antihypertensive efficacy of fixed-dose
      combination irbesartan 300 mg/amlodipine 5 mg (I300/A5) was superior to that of
      irbesartan (I300) monotherapy in lowering home systolic blood pressure after 10
      weeks' treatment. METHODS: The I-ADD study was a 10-week, multicenter, Phase III,
      prospective, randomized, parallel-group, open-label with blinded-end point study.
      The main inclusion criterion was essential uncontrolled hypertension (systolic
      blood pressure >=145 mm Hg at office after at least 4 weeks of irbesartan 150 mg
      [I150] monotherapy administered once daily). Patients continued to receive I150
      for 7 to 10 days and were randomized to either monotherapy with I150 for 5 weeks
      then I300 for the next 5 weeks, or to a fixed-dose combination therapy (I150/A5,
      then I300/A5). Safety profile was assessed by recording adverse events reported
      by patients or observed by the investigator. RESULTS: Following enrollment, 325
      patients were randomized to treatment, and 320 (mean [SD] age, 56.7 [11.4] years;
      41% male) were included in the intention-to-treat analysis: 155 patients treated
      with I150/A5 then I300/A5, and 165 patients treated with I150 then I300. At
      randomization, mean home systolic blood pressure was similar in both groups:
      152.7 (11.8) mm Hg in the I150/A5 group and 150.4 (10.1) mm Hg in the I150 group.
      At week 10, the adjusted mean difference in home systolic blood pressure between
      groups was -8.8 (1.1) mm Hg (P < 0.001). The percentage of controlled patients
      (mean home blood pressure <135 and 85 mm Hg) was nearly 2-fold higher in the
      I300/A5 group versus the I300 group (P < 0.001). Treatment-emergent adverse
      events were experienced by 10.5% of I300/A5-treated patients and 6.6% of I300
      treated patients during the second 5-week period. Three serious adverse events
      were reported; 2 with monotherapy (1 with I150 and 1 with I300) and 1 with fixed
      dose combination I300/A5. All patients affected by serious adverse events made a
      full recovery. CONCLUSIONS: These 10-week data from this patient population
      suggest a greater antihypertensive efficacy of the fixed-dose combination I300/A5
      over I300 alone in lowering systolic blood pressure. Both treatments were well
      tolerated throughout the study. ClinicalTrials.gov identifier: NCT00957554.

PMID- 22853853
TI  - The genetic correlation between cigarette smoking and alcohol drinking among
      Chinese adult male twins: an ordinal bivariate genetic analysis.
AB  - BACKGROUND: Though multiple policies have been implemented, the cigarette control
      in China is still facing a great challenge. At the same time, alcohol drinking
      has increasingly become a public health problem. Considering cigarette smoking
      and alcohol drinking often co-occur, a few studies tested the covariance of these
      phenotypes. However, the genetic and environmental correlation between them among
      Chinese population has not been determined. The main aim of this study is to fill
      this gap. METHODS: From the Chinese National Twin Registry, we obtained the data
      on cigarette smoking and alcohol drinking behaviors. The ordinal bivariate
      genetic analysis was performed to fit the categorical variables. After
      identifying the best decomposition among the Cholesky, common, and independent
      pathway model, we established the most parsimonious submodel. RESULTS: The
      correlation between current tobacco and alcohol use could be explained by
      Cholesky model. The shared environmental variances for both phenotypes were
      dropped to construct the most parsimonious submodel. Furthermore, the most
      parsimonious submodel showed a moderate correlation (0.32, 95%CI=0.17-0.46)
      between the genetic components and a negligible non-shared environmental
      correlation. CONCLUSION: As the first bivariate genetic analysis on current
      tobacco smoking and current alcohol drinking in China, this study suggested a
      common genetic vulnerability to tobacco and alcohol use in male twins. Further
      studies should be carried out to track the pertinent genes that are related to
      the comorbidity of smoking and drinking in Chinese population. Another urgent
      need is to recognize the behavior-specific environmental risk factors.

PMID- 22853851
TI  - Long term results of a prospective dose escalation phase-II trial: interstitial
      pulsed-dose-rate brachytherapy as boost for intermediate- and high-risk prostate
      cancer.
AB  - PURPOSE: We reviewed our seven year single institution experience with pulsed
      dose rate brachytherapy dose escalation study in patients with intermediate and
      high risk prostate cancer. MATERIALS AND METHODS: We treated a total of 130
      patients for intermediate and high risk prostate cancer at our institution
      between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external
      beam radiation therapy to 50.4 Gy. The majority of patients had T2 disease (T1c
      6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients
      had high-risk disease according to the D'Amico classification. The dose of the
      brachytherapy boost was escalated from 25 to 35 Gy - 33 pts. received 25 Gy
      (total dose 75 Gy), 63 pts. 30 Gy (total dose 80 Gy) and 34 pts. 35 Gy, (total
      dose 85 Gy) given in one session (dose per pulse was 0.60 Gy or 0.70 Gy/h, 24h
      per day, night and day, with a time interval of 1h between two pulses). PSA
      recurrence-free survival according to Kaplan-Meier using the Phoenix definition
      of biochemical failure was calculated and also late toxicities according to
      Common Toxicity Criteria scale were assessed. RESULTS: At the time of analysis
      with a median follow-up of 60 months biochemical control was achieved by 88% of
      patients - only 16/130 patients (12.3%) developed a biochemical relapse.
      Biochemical relapse free survival calculated according to Kaplan-Meier for all
      patients at 5 years was 85.6% (83.9% for intermediate-risk patients and 84.2% for
      high-risk patients) and at 9 years' follow up it was 79.0%. Analysing biochemical
      relapse free survival separately for different boost dose levels, at 5 years it
      was 97% for the 35 Gy boost dose and 82% for the 25 and 30 Gy dose levels. The
      side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2
      rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade
      1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a
      bulbourethral stricture requiring dilation or new onset incontinence.
      CONCLUSIONS: Image-guided conformal PDR-brachytherapy using up to 35 Gy as boost
      dose after 50 Gy of external beam radiation therapy (total dose up to 85 Gy) is a
      very effective treatment option with very low morbidity in patients with
      intermediate or high risk prostate cancer. Further dose escalation seems
      possible.

PMID- 22853852
TI  - Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated
      radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a
      randomized controlled trial.
AB  - PURPOSE: To compare three-dimensional conformal radiotherapy (3D-CRT) with
      intensity modulated radiation therapy (IMRT) in curative-intent irradiation of
      head-neck squamous cell carcinoma (HNSCC). METHODS: Previously untreated patients
      with biopsy-proven squamous carcinoma of oropharynx, larynx, or hypopharynx (T1
      3, N0-2b) were randomly assigned using computer-generated permuted-block design
      to either 3D-CRT or IMRT, with incidence of physician-rated Radiation Therapy
      Oncology Group (RTOG) grade 2 or worse acute salivary gland toxicity as primary
      end-point. RESULTS: Between 2005 and 2008, 60 patients randomly allocated to
      either 3D-CRT (n=28 patients) or IMRT (n=32) were included and analyzed on an
      intention-to-treat basis. The proportion [95% confidence intervals (CI)] of
      patients with RTOG grade 2 or worse acute salivary gland toxicity was
      significantly lesser in the IMRT arm [19 of 32 patients (59%, 95%CI: 42-75%)] as
      compared to 3D-CRT [25 of 28 patients (89%, 95%CI: 72-97%; p=0.009)]. Late
      xerostomia and subcutaneous fibrosis were also significantly lesser with IMRT.
      There was significant recovery of salivary function over time in patients treated
      with IMRT (p-value for trend=0.0036). At 3-years, there were no significant
      differences in loco-regional control or survival between the two arms.
      CONCLUSION: IMRT significantly reduces the incidence and severity of xerostomia
      compared to 3D-CRT in curative-intent irradiation of HNSCC.

PMID- 22853854
TI  - The effect of genetic background and dose on non-targeted effects of radiation.
AB  - PURPOSE: This work investigates the hypothesis that genetic background plays a
      significant role in the signalling mechanisms underlying induction and
      perpetuation of genomic instability following radiation exposure. MATERIALS AND
      METHODS: Bone marrow from two strains of mice (CBA and C57) were exposed to a
      range of X-ray doses (0, 0.01, 0.1, 1 and 3 Gy). Different cellular signalling
      endpoints: Apoptosis, cytokine levels and calcium flux, were evaluated at 2 h, 24
      h and 7 d post-irradiation to assess immediate and delayed effects. RESULTS: In
      CBA (radiosensitive) elevated apoptosis levels were observed at 24 h post X
      irradiation, and transforming growth factor-beta (TGF-beta) levels which
      increased with time and dose. C57 showed a higher background level of apoptosis,
      and sustained apoptotic levels 7 days after radiation exposure. Levels of tumor
      necrosis factor-alpha (TNF-alpha were increased in C57 at day 7 for higher X-ray
      doses. TGF-beta levels were higher in CBA, whilst C57 exhibited a greater TNF
      alpha response. Calcium flux was induced in reporter cells on exposure to
      conditioned media from both strains. CONCLUSIONS: These results show genetic and
      dose specific differences in radiation-induced signalling in the initiation and
      perpetuation of the instability process, which have potential implications on
      evaluation of non-targeted effects in radiation risk assessment.

PMID- 22853855
TI  - One-stage, totally laparoscopic major hepatectomy and colectomy for colorectal
      neoplasm with synchronous liver metastasis: safety, feasibility and short-term
      outcome.
AB  - BACKGROUND: Simultaneous surgery for primary colorectal tumor with synchronous
      liver metastasis has been showed to be safe and effective. One-stage, totally
      laparoscopic colorectal and minor liver resections have been reported, but there
      are no data regarding patients requiring simultaneous major hepatectomies and
      colorectal surgery. We aimed to evaluate the safety, feasibility and short-term
      outcomes of a small cohort of highly selected patients treated by 1-stage,
      totally laparoscopic major hepatectomy and colorectal resection. METHODS: From
      January 2009 to July 2011, 5 patients (3 women and 2 men) with primary colorectal
      neoplasm and synchronous monolobar liver metastasis requiring a major hepatectomy
      underwent attempt of 1-stage, totally laparoscopic approach after neoadjuvant
      chemotherapy. A retrospective analysis of prospective collected data was
      performed. RESULTS: There were no conversions to open procedures. All the
      patients but 1 underwent a 1-stage laparoscopic resection. Among these, liver
      procedures were 3 right and 1 left hepatectomy; colonic procedures were 3
      sigmoidectomies and 1 anterior resection of the rectum. Median operative time was
      495 minutes, and duration of hospital stay, 6 days. Median estimated blood loss
      was 475 mL (range, 300-630) with no mortality observed. An R0 resection was
      always achieved. Median follow-up was 14 months (range, 7-20) with 1 recurrence
      observed in the liver. CONCLUSION: In highly selected patients, a totally
      laparoscopic approach is a feasible and safe option to treat primary colorectal
      neoplasm with synchronous liver metastasis requiring major hepatectomies. These
      results need to be validated by larger, prospective, randomized studies.

PMID- 22853856
TI  - Bone marrow-derived stromal cell therapy for traumatic brain injury is
      neuroprotective via stimulation of non-neurologic organ systems.
AB  - Bone marrow-derived mesenchymal stromal cells (MSCs) used as "MSC therapy" after
      traumatic brain injury act as remote "bioreactors" via stimulation of lung
      macrophages and augmention of T regulatory cell production by the spleen, leading
      to systemic increases in circulating anti-inflammatory cytokines and alteration
      of the locoregional milieu of the central nervous system. The altered
      intracerebral microenvironment leads to modulation of the resident microglia
      population, thereby stimulating an increase in the ratio of M2 (anti
      inflammatory) macrophage to M1 (proinflammatory) macrophage, and it is this
      effect that accounts for the observed neuroprotection.

PMID- 22853857
TI  - Lack of interleukin-1 signaling results in perturbed early vein graft wall
      adaptations.
AB  - BACKGROUND: Vein grafts fail as the result of wall maladaptations to surgical
      injury and hemodynamic perturbations. Interleukin-1 signaling has emerged as an
      important mediator of the vascular response to trauma and hemodynamically induced
      vascular lesions. We therefore hypothesized that interleukin-1 signaling drives
      early vein graft wall adaptations. METHODS: Using interleukin-1 type I receptor
      knockout (IL-1RI(-/-)) and wild-type (B6129SF2/J) mice, we investigated
      morphologic changes 28 days after interposition isograft from donor inferior vena
      cava to recipient carotid artery, without (n = 19) or with (n = 13) outflow
      restriction. The impact of mouse strain on the response to vein arterialization
      also was evaluated between B6129SF2/J (n = 18) and C57BL/6J (n = 19) mice.
      RESULTS: No differences were observed in the traditional end points of intimal
      thickness and calculated luminal area, yet media+adventitia thickness of the vein
      graft wall of IL-1RI(-/-) mice was 44% to 52% less than wild-type mice, at the
      both proximal (P < .01, P < .01) and distal (P = .054, P < .01) portions of vein
      grafts, for both normal flow and low flow, respectively. Compared with the
      C57BL/6J strain, B6129SF2/J mice exhibited no difference in vein graft intimal
      thickness but 2-fold greater media+adventitia thickness (P < .01). CONCLUSION:
      When lacking IL-1 signaling, the vein graft wall adapts differently compared with
      the injured artery, showing typical intima hyperplasia although attenuated
      media+adventitia thickening. B6129SF2/J mice exhibit more media+adventitia
      response than C57BL/6J mice. The inflammatory networks that underlie the vein
      response to arterialization hold many roles in the adaptation of the total wall;
      thus, the utility of anti-inflammatory approaches to extend the durability of
      vein grafts comes into question.

PMID- 22853858
TI  - Virotherapy using a novel chimeric oncolytic adenovirus prolongs survival in a
      human pancreatic cancer xenograft model.
AB  - INTRODUCTION: Pancreatic adenocarcinoma is an aggressive malignancy. Oncolytic
      adenoviruses (Ads) are modified genetically to target tumor cells while sparing
      normal cells. We modified the knob domain of the Ad serotype 5 with a serotype 3
      knob domain and incorporated the CXCR4 promoter to regulate Ad E1A gene
      expression (Ad5/3-CXCR4-E1A). These modifications were made to efficiently infect
      and lyse pancreatic tumors. METHODS: Human pancreatic cancer lines CFPAC-1, PANC
      1, AsPC-1, and BxPC-3 were obtained from the American Type Culture Collection.
      Efficiency of Ad infection in the cells was determined by the use of an Ad
      construct expressing the green fluorescence protein (GFP) marker in place of the
      E1A gene (Ad5/3-CXCR4-GFP) and quantified by flow cytometry. Oncolytic activity
      in the pancreatic cancer cells was determined with the Ad5/3-CXCR4-E1A oncolytic
      Ad by a crystal violet staining method. To determine the oncolytic effect in
      vivo, pancreatic cancer cells were implanted on the flanks of 40 SCID mice (4
      groups). Tumors were injected intratumorally for 3 days with Ad5/3-CXCR4-E1A, Ad5
      wild-type (a positive control), or phosphate-buffered saline (a no virus
      control). Tumor size, overall survival, and body condition scale score were
      recorded. Statistical analyses included the Kaplan-Meier survival curve, the log
      rank test, and one-way analysis of variance. RESULTS: The serotype 3 fiber
      modified Ad with the CXCR4 promoter (Ad5/3-CXCR4-E1A) was most efficient in
      infecting and lysing pancreatic cancer cells compared with an Ad containing an
      unmodified fiber knob (Ad5-CXCR4-E1A). Treatment of pancreatic tumor xenografts
      in vivo with Ad5/3-CXCR4-E1A group resulted in smaller tumors (P = .001), greater
      body condition scale score (P = .01), and greater survival time (P = .04) than
      the other treatment groups. CONCLUSION: Ad5/3-CXCR4-E1A treatment significantly
      prolonged survival in SCID mice pancreatic tumor xenografts. This novel construct
      represents a potential new therapy against pancreatic cancer.

PMID- 22853860
TI  - Radiofrequency ablation for large hepatic hemangiomas: initial experience and
      lessons.
AB  - OBJECTIVE: We aimed to assess the feasibility, safety, and efficacy of
      radiofrequency (RF) ablation for the treatment of large (>=5 cm in greatest
      diameter) hepatic hemangiomas. METHODS: Thirty-six patients (15 male, 21 female;
      mean age 50 years) with 41 hepatic hemangiomas >=5 cm in diameter were enrolled
      and treated with RF ablation attributable to the presence of enlargement tendency
      and/or persistent hemangioma-associated symptoms. Twenty patients had 24
      hemangiomas <10 cm, and 16 patients had 17 hemangiomas >=10 cm. Technical
      success, complications related to RF ablation, completed ablation, symptom
      relief, change in size of ablation zone, and recurrence of the residual tumor
      were analyzed. RESULTS: Of the 41 hemangiomas with a mean diameter 10 +/- 4 cm
      (range, 5-22 cm), 26 subcapsular lesions were treated with a laparoscopic
      approach, and 15 lesions located in liver parenchyma underwent a computed
      tomography-guided percutaneous approach. RF ablation was performed successfully
      in all patients. There were 62 complications related to the ablation in 22
      patients, including 6 of 20 patients with hemangiomas <10 cm and all the 16
      patients with hemangiomas >=10 cm. According to the Dindo-Clavien classification,
      2 complications (lower esophageal fistula and acute respiratory distress
      syndrome, Grade III and Grade IV, respectively) were major in 2 patients with
      hemangiomas >=10 cm; all the other were minor in 20 patients (Grade I). All the
      complications were recovered by conservative treatment. Thirty-eight (93%) of 41
      hepatic hemangiomas were ablated completely, including all the 24 lesions <10 cm
      and 14 of 17 lesions >=10 cm. All the symptoms related to hemangiomas disappeared
      (n = 22) or were ameliorated (n = 4) after ablation. The mean diameter of
      ablation zone was decreased to 6 +/- 3 cm (2-12 cm) in a mean follow-up period (X
      +/- SD) of 15 +/- 6 months (range, 6-24 months), without recurrence or
      enlargement of the 3 residual tumors. CONCLUSION: The present study supports RF
      ablation as an alternative treatment for hepatic hemangiomas >=5 cm (but smaller
      than 10 cm) for the low risk of complications and likelihood of complete
      ablation, but, in contrast, RF ablation appears to be an inappropriate method for
      hepatic hemangiomas >=10 cm because of the high occurrence rate of complications.

PMID- 22853859
TI  - Increased phospholipase A2 and lyso-phosphatidylcholine levels are associated
      with surfactant dysfunction in lung contusion injury in mice.
AB  - OBJECTIVE: Surfactant dysfunction is an important pathologic disturbance in
      various forms of acute inflammatory lung injury. Previously we reported the
      presence of marked alterations in the composition and activity of pulmonary
      surfactant in bilateral lung contusions (LC) injury induced by blunt trauma in
      rats. This is extended here to a mouse model of unilateral LC with a focus on
      compositional and functional changes in surfactant associated with permeability
      injury and increases in activity of secretory phospholipase A2. RESULTS:
      Surfactant-associated gene expression was not altered in mice with unilateral LC
      injury on the basis of Affymetrix analysis. LC mice had significant permeability
      injury with increased albumin and total protein in bronchoalveolar lavage at 5,
      24, 48, and 72 hours after insult compared with uninjured controls. The percent
      content of large surfactant aggregates was depleted at all postinjury times, and
      pulmonary pressure-volume (P-V) mechanics and compliance were abnormal during
      this period. Surfactant dysfunction was evaluated in 24 hours, when permeability
      injury and P-V changes were most prominent. At this time, activity levels of
      secretory phospholipase A2 were increased in bronchoalveolar lavage, and
      chromatographic analysis showed that large surfactant aggregates had decreased
      levels of phosphatidylcholine and increased levels of lyso-phosphatidylcholine.
      These changes were accompanied by severe detriments in large aggregate surface
      activity by pulsating bubble surfactometry. Large aggregates from LC mice at 24
      hours had minimum surface tensions of only 12.6 +/- 1.1 mN/m after prolonged
      bubble pulsation (20 min) compared with 0.7 +/- 0.03 mN/m for uninjured controls.
      CONCLUSION: These results document important detriments in the composition and
      activity of pulmonary surfactant in LC injury in mice and suggest that active
      synthetic phospholipase-resistant exogenous surfactants may have utility in
      treating surfactant dysfunction in this clinically important condition.

PMID- 22853862
TI  - Letter to the editor.

PMID- 22853861
TI  - Effect of gastric versus post-pyloric feeding on the incidence of pneumonia in
      critically ill patients: observations from traditional and Bayesian random
      effects meta-analysis.
AB  - BACKGROUND & AIMS: Administration of enteral feeding is associated with a higher
      risk of nosocomial pneumonia. Herein, we systematically review the impact of
      gastric versus post-pyloric feeding on the incidence of pneumonia. METHODS: We
      searched the MEDLINE, EMBASE, Web of Science, and CCTRD (1966 to August 2011) for
      studies comparing gastric and post-pyloric feeding in critically ill patients.
      Two reviewers reviewed the quality of the studies and performed data extraction
      independently. Main outcome measures were the incidence of nosocomial pneumonia,
      aspiration, and vomiting. The meta-analysis was performed using traditional and
      Bayesian random-effects model. RESULTS: Our initial searches yielded 563 studies.
      Of these, we identified 15 randomized clinical trials enrolling 966 participants.
      Post-pyloric feeding was associated with reduction in pneumonia compared with
      gastric feeding (relative risk [RR] 0.63, 95% confidence interval [CI] 0.48-0.83,
      p = 0.001; I2 = 0%). The risk of aspiration (RR, 1.11; 95% CI, 0.80-1.53, p =
      0.55; I2 = 0%) and vomiting (RR, 0.80; 95% CI, 0.38-1.67, p = 0.56; I2 = 65.3%)
      were not significantly different between patients treated with gastric and post
      pyloric feeding. CONCLUSIONS: Comparing with gastric feeding, post-pyloric route
      can reduce incidence of pneumonia in critically ill patients.

PMID- 22853863
TI  - Encephalitozoon and Enterocytozoon (Microsporidia) spores in stool from pigeons
      and exotic birds: microsporidia spores in birds.
AB  - Microsporidia are considered to be a cause of emerging and opportunistic
      infections in humans, and the species that infect humans can also infect a wide
      range of animals, raising concerns for zoonotic transmission. To understand the
      role of birds in the transmission of diseases caused by microsporidia, we
      examined 196 fecal specimens from birds, including birds of the families
      Psittacidae, Emberizidae, Icteridae and Columbidae, using Gram-chromotrope stain
      and polymerase chain reaction (PCR). Of the 196 fecal samples surveyed, 48
      (24.5%) tested positive for microsporidia. The prevalence of microsporidia
      infection was higher in pigeons (31.1%) than in other birds (18.8%). The species
      of microsporidia that were detected in the birds surveyed in this study included
      Encephalitozoon hellem (found in 16.3% of positive samples), Enterocytozoon
      bieneusi (5.6%), Encephalitozoon intestinalis (1.5%) and Encephalitozoon cuniculi
      (1%). All the internal transcribed spacer (ITS) sequence of the rRNA from the
      study samples matched (with 100% identity) their correlate reference genotypes in
      GenBank, which included E. hellem 1A (AF338367), E. hellem 3 (AF110328), E.
      cuniculi I (AF338410) and E. bieneusi EpbA (AF076040). No fecal sample contained
      more than one type of microsporidian species. This study implicates exotic birds
      and pigeons as potential sources of microsporidia infection for humans living in
      urban areas.

PMID- 22853864
TI  - Performance of commercial ELISA and agglutination test kits for the detection of
      anti-Toxoplasma gondii antibodies in serum and muscle fluid of swine infected
      with 100, 300, 500 or 1000 oocysts.
AB  - Serum and tissue fluid samples from experimentally infected swine were tested for
      antibodies to Toxoplasma gondii using both an indirect ELISA and a modified
      agglutination test (MAT) available commercially in kit form. Ten 8-9 week-old
      swine were fed meatballs containing 100, 300, 500 or 1000 T. gondii oocysts and
      three control animals were fed meatballs with no oocysts. Post-inoculation blood
      samples were collected weekly until euthanasia at 35-63 days post inoculation
      (DPI). Tissue fluid was obtained from diaphragm, heart and sternomastoideus
      muscles post-mortem. By 16 DPI, nine of 10 inoculated pigs were detected
      serologically using ELISA at a pre-test serum dilution of 1:50 and all ten pigs
      were detected by the MAT at a serum dilution of 1:25. The last pig became
      positive on ELISA by 21 DPI and the 10 pigs maintained their serological status
      for the duration of the experiment. Heart muscle was the best overall source of
      tissue fluid for ELISA and all six pigs inoculated with either 500 or 1000
      oocysts were positive using either diaphragm or heart tissue fluid samples.
      However, 10 of 18 fluid samples from pigs receiving <= 300 oocysts were not
      detected using ELISA, including 5 of 6 from sternomastoideus muscle. The MAT used
      at a 1:10 pre-test dilution of tissue fluid correctly identified all 10
      inoculated pigs regardless of the source muscle. Based on these data, we conclude
      that either assay would be useful for herd evaluation or surveillance testing
      using sera, and the MAT would be a good candidate assay for testing tissue fluid
      for the same purposes.

PMID- 22853865
TI  - Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy
      Korean volunteers.
AB  - OBJECTIVE: Fesoterodine is a pro-drug of the active metabolite 5-hydroxymethyl
      tolterodine (5-HMT), a muscarinic receptor antagonist. This study aimed to
      evaluate the safety profile and pharmacokinetic characteristics of multiple oral
      doses of sustained-release fesoterodine (fesoterodine SR) in healthy Korean
      males. METHODS: A randomized, double-blind, placebo-controlled, multiple-dose
      study with two oral doses (4 mg and 8 mg) was conducted in healthy Korean male
      participants. The study drug was administered once daily for 5 days. The plasma
      concentration of 5-HMT was measured up to 72 hours after the last drug
      administration. The CYP2D6 genotype was analyzed using polymerase chain reaction
      (PCR) methods to assess the effect of genetic polymorphisms on the
      pharmacokinetic parameters. RESULTS: 20 participants completed the study. The
      mean (SD) areas under the plasma concentration-time curves during the dosing
      interval (AUCtau) of the 4 mg and 8 mg dose groups were 26.1 (8.0) and 64.2
      (30.5) MUg.h/ml and the mean peak concentrations (Cmax) were 2.6 (0.7) and 6.0
      (2.0) MUg/ml, respectively, at steady-state. The mean AUCtau and Cmax of 5-HMT
      increased in approximately the same proportion as the dose increased.
      Fesoterodine SR was well tolerated without any serious adverse events or abnormal
      clinical laboratory findings. CONCLUSION: Systemic 5-HMT exposure showed dose
      proportional characteristics in the 4 mg to 8 mg dose range in healthy Korean
      males. Thus, 4 mg or 8 mg doses of fesoterodine SR taken once-daily were
      tolerable in healthy Korean males.

PMID- 22853866
TI  - Successful treatment with erlotinib after gefitinib-induced interstitial lung
      disease: a case report and literature review.
AB  - Gefitinib and erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs), are widely used anticancer drugs for patients with non-small
      cell lung cancer (NSCLC), especially for those with EGFR-activating mutations.
      Both agents are considered to be less toxic compared with cytotoxic drugs;
      however, serious adverse events including interstitial lung disease (ILD) which
      can be fatal occur rarely. After such an event, physicians avoid to use another
      TKI. In such cases, patients and physicians are forced to make difficult
      decisions or reluctantly choose TKI when there is no other option. Here we report
      a case of a patient with lung adenocarcinoma who showed good recovery from
      gefitinib-induced ILD by high-dose corticosteroid therapy. The patient was then
      administrated erlotinib as second-line chemotherapy and showed tumor shrinkage
      without ILD after 6 months of treatment. We discuss the common features of the
      cases in the previous documentations and ours which were successfully retreated
      with erlotinib after gefitinib-induced ILD had previously developed.

PMID- 22853867
TI  - Pharmacogenomic/pharmacokinetic assessment of a four-probe cocktail for CYPs and
      OATPs following oral microdosing.
AB  - OBJECTIVES: To test whether the multiple phenotype and genotype relationships
      established using therapeutic dose, can be reproduced following oral microdosing
      using substrates of CYP2C9 (warfarin and glibenclamide), CYP2C19 (lansoprazole),
      CYP2D6 (dextromethorphan), and OATPs (glibenclamide). METHODS: A cocktail of test
      drugs was administered orally under the microdose in liquid or capsule form, and
      then a therapeutic dose of dextromethorphan was administered to 17 healthy
      subjects whose genotypes for CYPs and OATPs had been prescreened. Concentrations
      of the drugs and their metabolites were measured by LC-MS/MS. RESULTS: The AUC
      and t1/2 of glibenclamide following the microdosing tended to be higher and
      longer, respectively, in CYP2C9*1/*3 than CYP2C9*1/*1 subjects. In contrast,
      there were no significant differences in any of the pharmacokinetic parameters
      for warfarin between the two genotypes. For CYP2D6 following the therapeutic
      dose, there was good concordance between genotype and phenotype; however, such
      relationships disappeared after microdosing. For CYP2C19 following the
      microdosing, there were significant differences between EMs and PMs in the
      pharmacokinetic parameters of lansoprazole. The relative AUC0-12 ratio of
      lansoprazole in EMs and PMs was 1:3.3 - 4.3. Among test drugs, phenotypic
      measurements of lansoprazole accorded well with the CYP2C19 genotype at the
      microdose as well as therapeutic dose. CONCLUSIONS: The present study suggests
      that 1) the sampling strategy should be optimized according to pharmacokinetic
      profiles of the test drugs following oral microdosing, and 2) microdosing can be
      applied to the pharmacogenomic study of CYP-specific drugs.

PMID- 22853868
TI  - Early prediction of histopathological response of rectal tumors after one week of
      preoperative radiochemotherapy using 18 F-FDG PET-CT imaging. A prospective
      clinical study.
AB  - BACKGROUND: Preoperative radiochemotherapy (RCT) is standard in locally advanced
      rectal cancer (LARC). Initial data suggest that the tumor's metabolic response,
      i.e. reduction of its 18 F-FDG uptake compared with the baseline, observed after
      two weeks of RCT, may correlate with histopathological response. This prospective
      study evaluated the ability of a very early metabolic response, seen after only
      one week of RCT, to predict the histopathological response to treatment. METHODS:
      Twenty patients with LARC who received standard RCT regimen followed by radical
      surgery participated in this study. Maximum standardized uptake value (SUV-MAX),
      measured by PET-CT imaging at baseline and on day 8 of RCT, and the changes in
      FDG uptake (DeltaSUV-MAX), were compared with the histopathological response at
      surgery. Response was classified by tumor regression grade (TRG) and by
      achievement of pathological complete response (pCR). RESULTS: Absolute SUV-MAX
      values at both time points did not correlate with histopathological response.
      However, patients with pCR had a larger drop in SUV-MAX after one week of RCT
      (median: -35.31% vs -18.42%, p = 0.046). In contrast, TRG did not correlate with
      DeltaSUV-MAX. The changes in FGD-uptake predicted accurately the achievement of
      pCR: only patients with a decrease of more than 32% in SUV-MAX had pCR while none
      of those whose tumors did not show any decrease in SUV-MAX had pCR. CONCLUSIONS:
      A decrease in DeltaSUV-MAX after only one week of RCT for LARC may be able to
      predict the achievement of pCR in the post-RCT surgical specimen. Validation in a
      larger independent cohort is planned.

PMID- 22853869
TI  - Suicide, alcoholism, and psychiatric illness among union forces during the U.S.
      Civil War.
AB  - Little is known about post-combat psychological reactions of warriors prior to
      the Twentieth Century. We estimated rates of suicide, alcohol abuse, and probable
      psychiatric illness among Union Forces during the U.S. Civil War via examination
      of data compiled by the Union Army. White active-duty military personnel suicide
      rates ranged from 8.74 to 14.54 per 100,000 during the war, and surged to 30.4
      the year after the war. For blacks, rates ranged from 17.7 in the first year of
      their entry into the war (1863), to 0 in their second year, and 1.8 in the year
      after the war. Rates for most other relevant domains, including chronic
      alcoholism, "nostalgia," and insanity, were extremely low (<1.0%) by modern day
      standards. Data provide contextual information on suicide and psychiatric
      variables for combatants during the U.S. Civil War, a brutal modern war with
      vastly higher casualty rates than recent wars in Iraq and Afghanistan.

PMID- 22853870
TI  - On the different scenarios of disagreement between self- and informant-reports on
      an aged adults ability to perform activities of daily living.
AB  - BACKGROUND: Studies assessing physical functionality with questions on ability to
      perform activities of daily living (ADLs) commonly make use of self- and
      informant-report measures. OBJECTIVES: Delineate the scenarios from which
      disagreement can arise and show evidence for the presence of disagreements when
      reporting on ADLs. METHOD: Use information from a cross sectional study of
      community-dwelling minority aged adults and their informants to show how
      disagreement can arise in survey studies. RESULTS: Although disagreement between
      self and informant reports on ADLs exist, informants should be considered a
      reliable source of information. CONCLUSION: Informant reports should be used with
      caution when assessing complex and private ADLs.

PMID- 22853871
TI  - Differences in fear of falling in the elderly with or without dizzines.
AB  - To compare prevalence and risk factors associated with fear of falling (FoF) in
      two groups of elderly people, 109 patients with recurrent dizziness and 109
      controls without dizziness. FoF was defined as a positive response to the single
      question and with Falls Efficacy Scale of >50. The prevalence of FoF was greater
      (71.6%) in the dizzy group (control, 31.2%; p<0.001). Factors associated with FoF
      in the dizzy-group were diabetes, high General Health Questionnaire (GHQ-28)
      score and poor balance score. In the non-dizzy group, female gender, high GHQ,
      and poor gait score in Tinetti's scale were the association. Further research is
      needed to explore the relationship between dizziness and FoF.

PMID- 22853872
TI  - Linking COURAGE in Europe built environment instrument to the International
      Classification of Functioning, Disability and Health for Children and Youth (ICF
      CY).
AB  - OBJECTIVES: The aim of the paper is to prove that the COURAGE in Europe Built
      Environment (CBE) instrument selected items are relevant to health and disability
      assessment and evaluation. STUDY DESIGN: The two lists of the CBE preliminary
      items--outdoor checklist and self-reported questionnaire--were linked to the
      World Health Organization's International Classification of Functioning,
      Disability and Health for Children and Youth (ICF-CY) through established linking
      rules. RESULTS: The pool of the CBE 162 preliminary items were linked to a total
      of 184 categories of ICF-CY, and belonged mainly to two out of the four of the
      ICF-CY components. Fifteen of the items were not linked to any category of the
      ICF-CY classification at all. The linking process showed that more than 90% of
      CBE preliminary items were linked to ICF-CY categories and more than 4/5 of them
      were linked to the ICF-CY component of environmental factors. CONCLUSION: The
      fact that most of the linked CBE preliminary items referred to few ICF
      categories, on one hand showed that the ICF framework encompasses a lot of
      different aspects related to functioning and disability; on the other hand ICF
      categories are not very detailed for a comprehensive description of the built
      environment features.

PMID- 22853873
TI  - The effectiveness of a group psycho-educational program on family caregiver
      burden of patients with mental disorders.
AB  - BACKGROUND: Brief family intervention may have a positive impact on family
      caregivers for patients with mental disorders. We assessed the effectiveness of a
      group psycho-educational program on family caregivers for patients with
      schizophrenia and mood disorders. METHODS: This randomized controlled trial was
      performed on 100 caregivers for patients with mental disorders attending the
      Isfahan Behavioral Sciences Research Center (IBSRC), in Isfahan, Iran. One
      hundred family caregivers of patients with schizophrenia (n = 50) and mood
      disorders (n = 50) were selected and assigned randomly to either a psycho
      educational group intervention or routine care in each diagnosis category. The
      caregivers were followed for 3 months. Caregiver burden was assessed using the
      Zarit Burden Interview RESULTS: The mean scores of the Zarit caregiver burden
      decreased significantly for the group that participated in the psycho-educational
      program, while scores in the control group did not change significantly.
      CONCLUSIONS: This group intervention program was effective to reduce the
      caregiver burden for both categories of mental disorders in the Iranian
      population. This group intervention program may improve the quality of life of
      patients and caregivers by improving the standards of care giving. TRIAL
      REGISTRATION: RCT registration number: IRCT138804272200N.

PMID- 22853874
TI  - Application of nuclear magnetic relaxation to elucidate proton location and
      dynamics in N...H...O hydrogen bonds.
AB  - The proton location and dynamics in a hydrogen bond in solution are fundamentally
      important for understanding the phenomenon of proton transfer (PT). In the
      present study, the proton location and its dynamics were explored for the NH form
      of the two PT tautomers of the Schiff base by analyzing the fluctuation of the
      (15)N-(1)H magnetic dipolar coupling by the PT as well as the NH reorientational
      motion. For this purpose, the (15)N and (13)C spin-lattice relaxation times were
      measured in dichloromethane or acetonitrile solutions of three Schiff bases with
      different substituents on the benzene moieties, N-(4,6
      dimethoxysalicylidene)methylamine (compound 1), N-(1-methylnitrilomethylidyne)-2
      naphthalenomethylamine (compound 2), and N-(3,5-dibromosalicylidene)-methylamine
      (compound 3). For the NH form of compound 2 in dichloromethane, the proton
      location shifted to the center between the nitrogen and oxygen atoms, as compared
      with the minimum of the PT potential surface derived from molecular orbital
      calculations. For the NH form of compound 3 in dichloromethane, the proton
      location shift was not observed, and the PT rate was significantly lower than the
      reorientation rate of the NH bond. The results are discussed in terms of the
      electronic effect of the substituents and the static and dynamic solvent effect.

PMID- 22853876
TI  - Exploring the role of 'enabling places' in promoting recovery from mental
      illness: a qualitative test of a relational model.
AB  - This paper presents findings drawn from a study of the role of "enabling places"
      in promoting recovery among a sample of 24 adults living with a mental illness in
      Melbourne, Australia. Featuring a mix of visual and qualitative methods, the
      study invited participants to identify local places and place-related activities,
      which they regarded as supportive of their own health and recovery. The aim was
      to determine how and under what circumstances local places support recovery, and
      the ways these places are identified and maintained. Consistent with the logic of
      "enabling places", the study yielded evidence indicating that the various places
      identified by participants promoted recovery by facilitating access to an array
      of social, material and/or affective resources. Participants indicated that they
      draw on these resources in support of activities and relationships vital to the
      everyday 'work' of recovery. The paper closes with a discussion of the ways such
      "enabling" resources may be mobilised in the delivery of novel 'place-based'
      mental health initiatives.

PMID- 22853875
TI  - A nomogram associated with high probability of malignant nodes in the surgical
      specimen after trimodality therapy of patients with oesophageal cancer.
AB  - BACKGROUND: The presence of malignant lymph nodes (+ypNodes) in the surgical
      specimen after preoperative chemoradiation (trimodality) in patients with
      oesophageal cancer (EC) portends a poor prognosis for overall survival (OS) and
      disease-free survival (DFS). Currently, none of the clinical variables highly
      correlates with +ypNodes. We hypothesised that a combination of clinical
      variables could generate a model that associates with high likelihood of +ypNodes
      after trimodality in EC patients. METHODS: We report on 293 consecutive EC
      patients who received trimodality therapy. A multivariate logistic regression
      analysis that included pretreatment and post-chemoradiation variables identified
      independent variables that were used to construct a nomogram for +ypNodes after
      trimodality in EC patients. RESULTS: Of 293 patients, 91 (31.1%) had +ypNodes. OS
      (p=0.0002) and DFS (p<0.0001) were shorter in patients with +ypNodes compared to
      those with -ypNodes. In multivariable analysis, the significant variables for
      +ypNodes were: baseline T-stage (odds ratio [OR], 7.145; 95% confidence interval
      [CI], 1.381-36.969; p=0.019), baseline N-stage (OR, 2.246; 95% CI, 1.024-4.926;
      p=0.044), tumour length (OR, 1.178; 95% CI, 1.024-1.357; p=0.022), induction
      chemotherapy (OR, 0.471; 95% CI, 0.242-0.915; p=0.026), nodal uptake on post
      chemoradiation positron emission tomography (OR, 2.923; 95% CI, 1.007-8.485;
      p=0.049) and enlarged node(s) on post-chemoradiation computerised tomography (OR,
      3.465; 95% CI, 1.549-7.753; p=0.002). The nomogram after internal validation
      using the bootstrap method (200 runs) yielded a high concordance index of 0.756.
      CONCLUSION: Our nomogram highly correlates with the presence of +ypNodes after
      chemoradiation, however, considerably more refinement is needed before it can be
      implemented in the clinic.

PMID- 22853877
TI  - Anti-plasmodial action of de novo-designed, cationic, lysine-branched,
      amphipathic, helical peptides.
AB  - BACKGROUND: A lack of vaccine and rampant drug resistance demands new anti
      malarials. METHODS: In vitro blood stage anti-plasmodial properties of several de
      novo-designed, chemically synthesized, cationic, amphipathic, helical, antibiotic
      peptides were examined against Plasmodium falciparum using SYBR Green assay.
      Mechanistic details of anti-plasmodial action were examined by
      optical/fluorescence microscopy and FACS analysis. RESULTS: Unlike the monomeric
      decapeptides {(Ac-GXRKXHKXWA-NH2) (X = F,DeltaF) (Fm, DeltaFm IC50 >100 MUM)},
      the lysine-branched,dimeric versions showed far greater potency {IC50 (MUM) Fd
      1.5 , DeltaFd 1.39}. The more helical and proteolytically stable DeltaFd was
      studied for mechanistic details. DeltaFq, a K-K2 dendrimer of DeltaFm and
      (DeltaFm)2 a linear dimer of DeltaFm showed IC50 (MUM) of 0.25 and 2.4
      respectively. The healthy/infected red cell selectivity indices were >35
      (DeltaFd), >20 (DeltaFm)2 and 10 (DeltaFq). FITC-DeltaFd showed rapid and
      selective accumulation in parasitized red cells. Overlaying DAPI and FITC
      florescence suggested that DeltaFd binds DNA. Trophozoites and schizonts
      incubated with DeltaFd (2.5 MUM) egressed anomalously and Band-3 immunostaining
      revealed them not to be associated with RBC membrane. Prematurely egressed
      merozoites from peptide-treated cultures were found to be invasion incompetent.
      CONCLUSION: Good selectivity (>35), good resistance index (1.1) and low
      cytotoxicity indicate the promise of DeltaFd against malaria.

PMID- 22853880
TI  - On the sources of methane to the Los Angeles atmosphere.
AB  - We use historical and new atmospheric trace gas observations to refine the
      estimated source of methane (CH(4)) emitted into California's South Coast Air
      Basin (the larger Los Angeles metropolitan region). Referenced to the California
      Air Resources Board (CARB) CO emissions inventory, total CH(4) emissions are 0.44
      +/- 0.15 Tg each year. To investigate the possible contribution of fossil fuel
      emissions, we use ambient air observations of methane (CH(4)), ethane (C(2)H(6)),
      and carbon monoxide (CO), together with measured C(2)H(6) to CH(4) enhancement
      ratios in the Los Angeles natural gas supply. The observed atmospheric C(2)H(6)
      to CH(4) ratio during the ARCTAS (2008) and CalNex (2010) aircraft campaigns is
      similar to the ratio of these gases in the natural gas supplied to the basin
      during both these campaigns. Thus, at the upper limit (assuming that the only
      major source of atmospheric C(2)H(6) is fugitive emissions from the natural gas
      infrastructure) these data are consistent with the attribution of most (0.39 +/-
      0.15 Tg yr(-1)) of the excess CH(4) in the basin to uncombusted losses from the
      natural gas system (approximately 2.5-6% of natural gas delivered to basin
      customers). However, there are other sources of C(2)H(6) in the region. In
      particular, emissions of C(2)H(6) (and CH(4)) from natural gas seeps as well as
      those associated with petroleum production, both of which are poorly known, will
      reduce the inferred contribution of the natural gas infrastructure to the total
      CH(4) emissions, potentially significantly. This study highlights both the value
      and challenges associated with the use of ethane as a tracer for fugitive
      emissions from the natural gas production and distribution system.

PMID- 22853879
TI  - The adenylate cyclase gene MaAC is required for virulence and multi-stress
      tolerance of Metarhizium acridum.
AB  - BACKGROUND: The efficacy of entomopathogenic fungi in pest control is mainly
      affected by various adverse environmental factors, such as heat shock and UV-B
      radiation, and by responses of the host insect, such as oxidative stress, osmotic
      stress and fever. In this study, an adenylate cyclase gene (MaAC) was cloned from
      the locust-specific entomopathogenic fungus, Metarhizium acridum, which is
      homologous to various fungal adenylate cyclase genes. RNA silencing was adapted
      to analyze the role of MaAC in virulence and tolerance to adverse environmental
      and host insect factors. RESULTS: Compared with the wild type, the vegetative
      growth of the RNAi mutant was decreased in PD (potato dextrose medium), Czapek
      dox and PDA plates, respectively, demonstrating that MaAC affected vegetative
      growth. The cAMP levels were also reduced in PD liquid culture, and exogenous
      cAMP restored the growth of RNAi mutants. These findings suggested that MaAC is
      involved in cAMP synthesis. The knockdown of MaAC by RNAi led to a reduction in
      virulence after injection or topical inoculation. Furthermore, the RNAi mutant
      grew much slower than the wild type in the haemolymph of locust in vitro and in
      vivo, thus demonstrating that MaAC affects the virulence of M. acridum via fungal
      growth inside the host locust. A plate assay indicated that the tolerances of the
      MaAC RNAi mutant under oxidative stress, osmotic stress, heat shock and UV-B
      radiation was decreased compared with the wild type. CONCLUSION: MaAC is required
      for virulence and tolerance to oxidative stress, osmotic stress, heat shock and
      UV-B radiation. MaAC affects fungal virulence via vegetative growth inside the
      insect and tolerance against oxidative stress, osmotic stress and locust fever.

PMID- 22853878
TI  - Nutrition and the psychoneuroimmunology of postpartum depression.
AB  - Postpartum depression (PPD) is a relatively common and often severe mood disorder
      that develops in women after childbirth. The aetiology of PPD is unclear,
      although there is emerging evidence to suggest a psychoneuroimmune connection.
      Additionally, deficiencies in n-3 PUFA, B vitamins, vitamin D and trace minerals
      have been implicated. This paper reviews evidence for a link between
      micronutrient status and PPD, analysing the potential contribution of each
      micronutrient to psychoneuroimmunological mechanisms of PPD. Articles related to
      PPD and women's levels of n-3 PUFA, B vitamins, vitamin D and the trace minerals
      Zn and Se were reviewed. Findings suggest that while n-3 PUFA levels have been
      shown to vary inversely with PPD and link with psychoneuroimmunology, there is
      mixed evidence regarding the ability of n-3 PUFA to prevent or treat PPD. B
      vitamin status is not clearly linked to PPD, even though it seems to vary
      inversely with depression in non-perinatal populations and may have an impact on
      immunity. Vitamin D and the trace minerals Zn and Se are linked to PPD and
      psychoneuroimmunology by intriguing, but small, studies. Overall, evidence
      suggests that certain micronutrient deficiencies contribute to the development of
      PPD, possibly through psychoneuroimmunological mechanisms. Developing a better
      understanding of these mechanisms is important for guiding future research,
      clinical practice and health education regarding PPD.

PMID- 22853881
TI  - Meconium peritonitis in both fetuses with early twin-to-twin transfusion
      syndrome.
AB  - Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin
      bloodflow through placental vascular anastomoses. We present a TTTS case treated
      with fetoscopic laser photocoagulation (FLP) that was complicated by perinatal
      meconium peritonitis in both twins. Ten weeks following laser treatment, the two
      fetuses showed intra-abdominal hyperechogenicity and ascites. After birth, the
      two newborns were surgically managed for peritonitis. We discuss the pathogenesis
      of this double insult. The present case highlights the role of end-circulation
      bowel thrombi as the potential cause of subsequent intestinal perforation.

PMID- 22853882
TI  - Fetal magnetic resonance imaging and three-dimensional ultrasound in clinical
      practice: applications in prenatal diagnosis.
AB  - Three-dimensional ultrasound and magnetic resonance imaging are powerful imaging
      techniques that are used increasingly in evaluating fetal anatomy. In this
      chapter, we review the main applications of these imaging modalities in current
      practice and present an overview of the malformations that may benefit from
      assessment with three-dimensional ultrasound and magnetic resonance imaging.

PMID- 22853883
TI  - Advances in fetal genetic diagnosis and therapy: ethical issues and appropriate
      technology in cost-restrained countries.
AB  - The advent of ultrasound in the 1970s heralded a milestone that could give real
      time information about fetal abnormalities, and thereby improve diagnostic
      accuracy. This knowledge could not be used effectively to benefit the fetus for
      which it was intended. The 1980s saw science catching up with diagnostic
      advances, and fetal abnormalities could realistically be treated with an
      expectation of satisfactory outcomes. As a result, parents could have realistic
      expectations of having healthy children. Prenatal diagnosis is the first step
      towards this realisation, as diagnosis can be followed by intrauterine treatment.
      Scientists have realised that, if an abnormality can be corrected prenatally,
      prognosis can be improved significantly, as the initial problem does not
      necessarily threaten the fetus; therefore, if the prenatal condition can be dealt
      with early, then the downstream repercussions can be eliminated. In this chapter,
      we address ethical issues in prenatal diagnosis and fetal therapy.

PMID- 22853884
TI  - Reasons why persons living with HIV include individuals in their chosen families.
AB  - HIV influences those with the disease as well as their families and social
      relationships. The chosen families of persons living with HIV (PLWH) provide
      structure, social support, and security. Our study identified reasons why PLWH
      included specific individuals in their chosen families (or families of choice).
      This mixed-method design used a convenience sample of 150 PLWH, ages 19-68 years.
      Self-reported reasons for including specific individuals in their chosen families
      were love and acceptance (n = 135; 90.0%), support (n = 100; 66.7%), blood and
      family ties (n = 37; 24.7%), and commonality (n = 28; 18.7%). Demographic and
      personal characteristics were unrelated to these themes, supporting the
      conclusion that reasons for choosing family members are universal across these
      variables. These findings emphasize the need for health care providers to
      encourage the development of friendships and relationships between PLWH and those
      who provide love and acceptance, support, blood/familial ties, and common
      interests.

PMID- 22853886
TI  - Collaboration between health professionals in the era of antiretroviral therapy.
AB  - After antiretroviral therapy (ART) became available in South Africa, persons
      living with HIV (PLWH) began to survive, but they often experienced disability as
      a result of their illness and treatments. Management of HIV is more often
      successful with a holistic approach including medicine, rehabilitation, and
      social care. There is limited literature on collaborations between nurses and
      allied health professionals in the rehabilitation of PLWH, with no documentation
      of partnerships between nurses and physiotherapists in high-HIV burdened
      countries. We investigated the collaboration between nurses and physiotherapists
      in the rehabilitation of PLWH. We conducted two focus groups with experienced
      nurses at two residential facilities for PLWH in KwaZulu-Natal, South Africa,
      using Van Manen's pedagogy on interpretive phenomenology as the conceptual
      framework. Three barriers to collaboration were found: role governance,
      environmental structure, and organizational variance. Education and in-service
      programs and workshops were suggested to curb the divide.

PMID- 22853885
TI  - A systematic review of probiotics as a potential intervention to restore gut
      health in HIV infection.
AB  - Probiotics have beneficial effects on the gut in numerous conditions. The purpose
      of this paper is to present a review of the current literature on probiotics used
      in chronic illnesses exhibiting similar pathology seen in HIV gut dysfunction, in
      order to make recommendations for their use to promote and restore healing of the
      gut with subsequent reduction of ongoing inflammation caused by microbial
      translocation. A review of the literature was performed, focusing on probiotics
      as an intervention to improve gut health. Key words were searched in PubMed and
      the Cumulative Index to Nursing and Allied Health Literature. The literature
      reviewed was limited to clinical trials, meta-analyses, and practice guidelines.
      The review provided evidence that probiotics were supportive in modulating
      aspects of gut physiology, barrier integrity, and immune function. Probiotic use
      is a supportive adjunct therapy, worthy of consideration and further research in
      persons infected with HIV.

PMID- 22853887
TI  - Effect of a hippotherapy intervention program on static balance and strength in
      adolescents with intellectual disabilities.
AB  - The aim of this study was to assess the effects of a hippotherapy program on
      static balance and strength in adolescents with intellectual disability (ID).
      Nineteen adolescents with moderate ID were assigned either an experimental group
      (n=10) or a control group (n=9). The experimental group attended a 10-week
      hippotherapy program. To assess static balance, three tasks of increasing
      difficulty (Double-Leg Stance with opened or closed eyes, and One-Leg Stance with
      opened eyes) were performed while standing on an EPS pressure platform (Loran
      Engineering S.r.I., Bologna, Italy). The strength measurements consisted of three
      maximal isometric half-squats from the seating position (knee joint at 90 degrees
      ). The hippotherapy intervention program resulted in significant improvements in
      strength parameters, and on the more complex balance task (i.e. standing on one
      leg). In conclusion, this study provides evidence that hippotherapy can be used
      as an effective intervention for improving balance and strength in individuals
      with ID, and could thus influence functional activities and quality of life.

PMID- 22853888
TI  - Can psychopathology at age 7 be predicted from clinical observation at one year?
      Evidence from the ALSPAC cohort.
AB  - One of the challenges of developmental psychopathology is to determine whether
      identifiable pathways to developmental disorders exist in the first months or
      years of life. Early identification of such disorders poses a similar challenge
      for clinical services. Using data from a large contemporary birth cohort, we
      examined whether psychopathology at age seven can be predicted from clinician
      observation at one year. Two groups of clinical raters observed videos of
      caregiver-infant interaction. Neither group of raters could reliably identify any
      precursors of later development of psychopathology in the one-year-old infants in
      this setting.

PMID- 22853890
TI  - Dissociating influences of key and hand separation on the Stroop color
      identification effect.
AB  - Three experiments examined the influence of distance between response keys (and
      hands) on the Stroop effect obtained for two-choice tasks in which stimulus
      colors were identified with keypresses. The Stroop effect was larger when the
      response locations were close together than when they were far apart, replicating
      a previous finding. Although this result was obtained only in the initial 30
      trials, it was evident in a between-subject design as well as a within-subject
      design. With more practice, the Stroop effect was of similar size for the close
      and far separation conditions. Also, when the keys were close together, the
      Stroop effect was of similar size regardless of whether they were actuated by
      fingers from one or two hands, providing evidence against anatomical
      discriminability as a critical factor. Finally, the Stroop effect was numerically
      larger when the close keys were pressed by sticks held at the far separation than
      when the far keys were pressed by sticks held at the close separation,
      implicating distance between the keys rather than the hands as the main factor.
      The initially larger Stroop effect in RT for close keys could be due to lower
      spatial discriminability or to an accuracy bias in response thresholds, as
      suggested by the finding that it was accompanied by a numerically smaller effect
      in percent error.

PMID- 22853889
TI  - Knee muscle strength at varying angular velocities and associations with gross
      motor function in ambulatory children with cerebral palsy.
AB  - The aim of this study was to evaluate the relationships of muscle strength at
      different angular velocities and gross motor functions in ambulatory children
      with cerebral palsy (CP). This study included 33 ambulatory children with spastic
      CP aged 6-15 years and 15 children with normal development. Children with CP were
      categorized into level I (n=17) or level II (n=16) according to Gross Motor
      Function Classification System (GMFCS) levels. All children underwent curl-up
      test and isokinetic tests of the knee extensor and flexor muscle. Children with
      CP underwent the gross motor function assessments, including the Gross Motor
      Function Measure (GMFM-66) and the gross motor subtests of Bruininks-Oseretsky
      Test of Motor Proficiency (BOTMP). The hamstring-quadriceps ratio (HQ ratio) was
      calculated as 100%*(isokinetic peak torque of hamstring (knee flexor)/isokinetic
      peak torque of quadriceps (knee extensor)). Children with GMFCS level II had
      lower BOTMP and GMFM-66 scores, curl-up scores, HQ ratio, and knee muscle
      strength, especially knee flexor, compared to those with GMFCS level I. The
      regression analysis showed that knee flexor torques at 60 and 90 degrees /s are
      mainly related to balance (r(2)=0.167, p=0.011) and strength (r(2)=0.243,
      p=0.002) while knee flexor torques at 120 degrees /s mainly contribute to running
      speed and agility (r(2)=0.372, p<0.001). These findings suggest that children
      with CP had knee strength deficits, especially knee flexor. Postural muscle (knee
      flexor) strength dominated gross motor function than antigravity muscle strength
      (knee extensor). The knee flexor strength at different angular velocities was
      associated with various gross motor tasks. The HQ ratio may be used as a
      potential biomarker to probe the therapeutic effectiveness for muscle
      strengthening in these children. These data may allow clinician for formulating
      effective muscle strengthening strategies for these children.

PMID- 22853891
TI  - Frontal cortex TMS for tinnitus.
AB  - Both invasive and non-invasive neuromodulation of the dorsolateral prefrontal
      cortex (DLPFC) are capable of suppressing tinnitus loudness. Repetitive
      transcranial magnetic stimulation (rTMS) of the DLPFC has an add-on effect for
      auditory cortex (AC) rTMS in improving tinnitus-related distress. We aimed to
      investigate whether TMS and rTMS of the DLPFC is capable of reducing tinnitus
      loudness and what mechanism might be involved. Two TMS studies targeting the
      right DLPFC were performed. Study 1 investigated 44 tinnitus patients who
      underwent either 1 or 10 Hz real or sham TMS (200 pulses at 80% motor threshold).
      In Study 2 we performed rTMS (10 sessions of 600 pulses) in responders of study
      1. Changes on the visual analog scale (VAS) loudness were evaluated. All patients
      underwent a pre-TMS electroencephalography: differences in functional
      connectivity between responders and non-responders were evaluated using sLORETA.
      Only 1 Hz TMS was capable of significantly reducing tinnitus loudness for 11
      patients with a mean suppression of 39.23%. RTMS for these 11 patients yielded a
      21% improvement in VAS loudness, and in 7 of 11 rTMS was successful, with, a mean
      suppression of 27.13%. The responders were characterized by a difference in
      lagged linear connectivity in the theta band among the DLPFC, anterior cingulate
      cortex (ACC), parahippocampus and AC. In summary, 1 H, TMS and rTMS of the right
      DLPFC can transiently reduce the perceived tinnitus loudness mediated via
      functional connections between the DLPFC and a network consisting of the ACC,
      parahippocampus and AC.

PMID- 22853892
TI  - Filling a gap in developmental toxicity testing: neural crest cells offer faster,
      cheaper, animal-free testing.

PMID- 22853893
TI  - Sensing and responding to membrane tension: the bacterial MscL channel as a model
      system.
AB  - Mechanosensors are important for many life functions, including the senses of
      touch, balance, and proprioception; cardiovascular regulation; kidney function;
      and osmoregulation. Many channels from an assortment of families are now
      candidates for eukaryotic mechanosensors and proprioception, as well as
      cardiovascular regulation, kidney function, and osmoregulation. Bacteria also
      possess two families of mechanosensitive channels, termed MscL and MscS, that
      function as osmotic emergency release valves. Of the two channels, MscL is the
      most conserved, most streamlined in structure, and largest in conductance at 3.6
      nS with a pore diameter in excess of 30 A; hence, the structural changes required
      for gating are exaggerated and perhaps more easily defined. Because of these
      properties, as well as its tractable nature, MscL represents a excellent model
      for studying how a channel can sense and respond to biophysical changes of a
      lipid bilayer. Many of the properties of the MscL channel, such as the
      sensitivity to amphipaths, a helix that runs along the membrane surface and is
      connected to the pore via a glycine, a twisting and turning of the transmembrane
      domains upon gating, and the dynamic changes in membrane interactions, may be
      common to other candidate mechanosensors. Here we review many of these properties
      and discuss their structural and functional implications.

PMID- 22853894
TI  - E-cadherin-dependent stimulation of traction force at focal adhesions via the Src
      and PI3K signaling pathways.
AB  - The interplay between cadherin- and integrin-dependent signals controls cell
      behavior, but the precise mechanisms that regulate the strength of adhesion to
      the extracellular matrix remains poorly understood. We deposited cells expressing
      a defined repertoire of cadherins and integrins on fibronectin (FN)-coated
      polyacrylamide gels (FN-PAG) and on FN-coated pillars used as a micro-force
      sensor array (MUFSA), and analyzed the functional relationship between these
      adhesion receptors to determine how it regulates cell traction force. We found
      that cadherin-mediated adhesion stimulated cell spreading on FN-PAG, and this was
      modulated by the substrate stiffness. We compared S180 cells with cells stably
      expressing different cadherins on MUFSA and found that traction forces were
      stronger in cells expressing cadherins than in parental cells. E-cadherin
      mediated contact and mechanical coupling between cells are required for this
      increase in cell-FN traction force, which was not observed in isolated cells, and
      required Src and PI3K activities. Traction forces were stronger in cells
      expressing type I cadherins than in cells expressing type II cadherins, which
      correlates with our previous observation of a higher intercellular adhesion
      strength developed by type I compared with type II cadherins. Our results reveal
      one of the mechanisms whereby molecular cross talk between cadherins and
      integrins upregulates traction forces at cell-FN adhesion sites, and thus provide
      additional insight into the molecular control of cell behavior.

PMID- 22853895
TI  - Mixed exciton-charge-transfer states in photosystem II: Stark spectroscopy on
      site-directed mutants.
AB  - We investigated the electronic structure of the photosystem II reaction center
      (PSII RC) in relation to the light-induced charge separation process using Stark
      spectroscopy on a series of site-directed PSII RC mutants from the cyanobacterium
      Synechocystis sp. PCC 6803. The site-directed mutations modify the protein
      environment of the cofactors involved in charge separation (P(D1), P(D2),
      Chl(D1), and Phe(D1)). The results demonstrate that at least two different
      exciton states are mixed with charge-transfer (CT) states, yielding exciton
      states with CT character: (P(D2)(delta)(+)P(D1)(delta)(-)Chl(D1)) (673 nm) and
      (Chl(D1)(delta)(+)Phe(D1)(delta)(-)) (681 nm) (where the subscript indicates the
      wavelength of the electronic transition). Moreover, the CT state P(D2)(+)P(D1)(-)
      acquires excited-state character due to its mixing with an exciton state,
      producing (P(D2)(+)P(D1)(-))(delta) (684 nm). We conclude that the states that
      initiate charge separation are mixed exciton-CT states, and that the degree of
      mixing between exciton and CT states determines the efficiency of charge
      separation. In addition, the results reveal that the pigment-protein interactions
      fine-tune the energy of the exciton and CT states, and hence the mixing between
      these states. This mixing ultimately controls the selection and efficiency of a
      specific charge separation pathway, and highlights the capacity of the protein
      environment to control the functionality of the PSII RC complex.

PMID- 22853896
TI  - Properties of intermediate filament networks assembled from keratin 8 and 18 in
      the presence of Mg2+.
AB  - The mechanical properties of epithelial cells are modulated by structural changes
      in keratin intermediate filament networks. To investigate the relationship
      between network architecture and viscoelasticity, we assembled keratin filaments
      from recombinant keratin proteins 8 (K8) and 18 (K18) in the presence of divalent
      ions (Mg(2+)). We probed the viscoelastic modulus of the network by tracking the
      movement of microspheres embedded in the network during assembly, and studied the
      network architecture using scanning electron microscopy. Addition of Mg(2+) at
      physiological concentrations (<1 mM) resulted in networks whose structure was
      similar to that of keratin networks in epithelial cells. Moreover, the elastic
      moduli of networks assembled in vitro were found to be within the same magnitude
      as those measured in keratin networks of detergent-extracted epithelial cells.
      These findings suggest that Mg(2+)-induced filament cross-linking represents a
      valid model for studying the cytoskeletal mechanics of keratin networks.

PMID- 22853897
TI  - Temperature and RyR1 regulate the activation rate of store-operated Ca2+ entry
      current in myotubes.
AB  - Store-operated calcium entry (SOCE) is an important Ca(2+) entry pathway in
      skeletal muscle. However, direct electrophysiological recording and full
      characterization of the underlying SOCE current in skeletal muscle cells
      (I(SkCRAC)) has not been reported. Here, we characterized the biophysical
      properties, pharmacological profile, and molecular identity of I(SkCRAC) in
      skeletal myotubes, as well as the regulation of its rate of activation by
      temperature and the type I ryanodine receptor (RyR1). I(SkCRAC) exhibited many
      hallmarks of Ca(2+) release activated Ca(2+) currents (I(CRAC)): store
      dependence, strong inward rectification, positive reversal potential, limited
      cesium permeability, and sensitivity to SOCE channel blockers. I(SkCRAC) was
      reduced by siRNA knockdown of stromal interaction molecule 1 and expression of
      dominant negative Orai1. Average I(SkCRAC) current density at -80mV was 1.00 +/-
      0.05 pA/pF. In the presence of 20 mM intracellular EGTA, I(SkCRAC) activation
      occurred over tens of seconds during repetitive depolarization at 0.5Hz and was
      inhibited by treatment with 100 MUM ryanodine. The rate of SOCE activation was
      reduced threefold in myotubes from RyR1-null mice and increased 4.6-fold at
      physiological temperatures (35-37 degrees C). These results show that I(SkCRAC)
      exhibits similar biophysical, pharmacological, and molecular properties as
      I(CRAC) in nonexcitable cells and its rate of activation during repetitive
      depolarization is strongly regulated by temperature and RyR1 activity.

PMID- 22853898
TI  - Population shift between the open and closed states changes the water
      permeability of an Aquaporin Z mutant.
AB  - Aquaporins are tetrameric transmembrane channels permeable to water and other
      small solutes. Wild-type (WT) and mutant Aquaporin Z (AqpZ) have been widely
      studied and multiple factors have been found to affect their water permeability.
      In this study, molecular dynamics simulations have been performed for the
      tetrameric AqpZ F43W/H174G/T183F mutant. It displayed ~10% average water
      permeability compared to WT AqpZ, which had been attributed to the increased
      channel lumen hydrophobicity. Our simulations, however, show a ring stacking
      between W43 and F183 acting as a secondary steric gate in the triple mutant with
      R189 as the primary steric gate in both mutant and WT AqpZ. The double gates
      (R189 and W43-F183) result in a high population of the closed conformation in the
      mutant. Occasionally an open state, with diffusive water permeability very close
      to that of WT AqpZ, was observed. Taken together, our results show that the
      double-gate mechanism is sufficient to explain the reduced water permeability in
      the mutant without invoking effects arising from increased hydrophobicity of the
      channel lumen. Our findings provide insights into how aquaporin-mediated water
      transport can be modulated and may further point to how aquaporin function can be
      optimized for biomimetic membrane applications.

PMID- 22853899
TI  - Drying transition in the hydrophobic gate of the GLIC channel blocks ion
      conduction.
AB  - The theoretical prediction of water drying transitions near nonpolar surfaces has
      stimulated an intensive search for biological processes exploiting this extreme
      form of hydrophobicity. Here we quantitatively demonstrate that drying of a
      hydrophobic constriction is the major determinant of ion conductance in the GLIC
      pentameric ion channel. Molecular-dynamics simulations show that in the closed
      state, the channel conductance is ~12 orders-of-magnitude lower than in the open
      state. This large drop in conductance is remarkable because even in the
      functionally closed conformation the pore constriction remains wide enough for
      the passage of sodium ions, aided by a continuous bridge of ~12 water molecules.
      However, we find that the free energy cost of hydrating the hydrophobic gate is
      large, accounting almost entirely for the energetic barrier blocking ion passage.
      The free energies of transferring a sodium ion into a prehydrated gate in
      functionally closed and open states differ by only 1.2 kcal/mol, compared to an
      11 kcal/mol difference in the costs of hydrating the hydrophobic gate.
      Conversely, ion desolvation effects play only minor roles in GLIC ion channel
      gating. Our simulations help rationalize experiments probing the gating kinetics
      of the nicotinic acetylcholine receptor in response to mutations of pore-lining
      residues. The molecular character and phase behavior of water should thus be
      included in quantitative descriptions of ion channel gating.

PMID- 22853900
TI  - Docosahexaenoic and eicosapentaenoic acids segregate differently between raft and
      nonraft domains.
AB  - Omega-3 polyunsaturated fatty acids (n-3 PUFA), enriched in fish oils, are
      increasingly recognized to have potential benefits for treating many human
      afflictions. Despite the importance of PUFA, their molecular mechanism of action
      remains unclear. One emerging hypothesis is that phospholipids containing n-3
      PUFA acyl chains modify the structure and composition of membrane rafts, thus
      affecting cell signaling. In this study the two major n-3 PUFA found in fish
      oils, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, are compared. Using
      solid-state (2)H NMR spectroscopy we explored the molecular organization of 1
      [(2)H(31)]palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC-d(31)) and 1
      [(2)H(31)]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d(31)) in mixtures
      with sphingomyelin (SM) and cholesterol (chol). Our results indicate that whereas
      both PEPC-d(31) and PDPC-d(31) can accumulate into SM-rich/chol-rich raftlike
      domains, the tendency for DHA to incorporate into rafts is more than twice as
      great as for EPA. We propose that DHA may be the more bioactive component of fish
      oil that serves to disrupt lipid raft domain organization. This mechanism
      represents an evolution in the view of how PUFA remodel membrane architecture.

PMID- 22853901
TI  - Mechanism for calcium ion sensing by the C2A domain of synaptotagmin I.
AB  - The C2A domain is one of two calcium ion (Ca(2+))- and membrane-binding domains
      within synaptotagmin I (Syt I), the identified Ca(2+) sensor for regulated
      exocytosis of neurotransmitter. We propose that the mechanistic basis for C2A's
      response to Ca(2+) and cellular function stems from marginal stability and ligand
      induced redistributions of protein conformers. To test this hypothesis, we used a
      combination of calorimetric and fluorescence techniques. We measured free
      energies of stability by globally fitting differential scanning calorimetry and
      fluorescence lifetime spectroscopy denaturation data, and found that C2A is
      weakly stable. Additionally, using partition functions in a fluorescence
      resonance energy transfer approach, we found that the Ca(2+)- and membrane
      binding sites of C2A exhibit weak cooperative linkage. Lastly, a dye-release
      assay revealed that the Ca(2+)- and membrane-bound conformer subset of C2A
      promote membrane disruption. We discuss how these phenomena may lead to both
      cooperative and functional responses of Syt I.

PMID- 22853902
TI  - Oxidized phosphatidylcholines promote phase separation of cholesterol
      sphingomyelin domains.
AB  - Lipid lateral segregation in the plasma membrane is believed to play an important
      role in cell physiology. Sphingomyelin (SM) and cholesterol (Chol)-enriched
      microdomains have been proposed as liquid-ordered phase platforms that serve to
      localize signaling complexes and modulate the intrinsic activities of the
      associated proteins. We modeled plasma membrane domain organization using
      Langmuir monolayers of ternary POPC/SM/Chol as well as DMPC/SM/Chol mixtures,
      which exhibit a surface-pressure-dependent miscibility transition of the
      coexisting liquid-ordered and -disordered phases. Using Brewster angle microscopy
      and Langmuir monolayer compression isotherms, we show that the presence of an
      oxidatively modified phosphatidylcholine, 1-palmitoyl-2-azelaoyl-sn-glydecero-3
      phosphocholine, efficiently opposes the miscibility transition and stabilizes
      micron-sized domain separation at lipid lateral packing densities corresponding
      to the equilibrium lateral pressure of ~32 mN/m that is suggested to prevail in
      bilayer membranes. This effect is ascribed to augmented hydrophobic mismatch
      induced by the oxidatively truncated phosphatidylcholine. To our knowledge, our
      results represent the first quantitative estimate of the relevant level of
      phospholipid oxidation that can potentially induce changes in cell membrane
      organization and its associated functions.

PMID- 22853903
TI  - Spontaneous formation of two-dimensional and three-dimensional cholesterol
      crystals in single hydrated lipid bilayers.
AB  - Grazing incidence x-ray diffraction measurements were performed on single
      hydrated bilayers and monolayers of Ceramide/Cholesterol/1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocyholine at varying concentrations. There are substantial
      differences in the phase and structure behavior of the crystalline domains formed
      within the bilayers relative to the corresponding monolayers, due to interactions
      between the opposing lipid leaflets. Depending on the lipid composition, these
      interactions lead to phase separation and formation of cholesterol crystals. The
      cholesterol and ceramide/cholesterol mixed phases were further characterized at
      37 degrees C by immunolabeling with specific antibodies recognizing ordered
      molecular arrays of cholesterol. Previous studies have shown that cholesterol may
      nucleate in artificial membranes to form thick two-dimensional bilayer crystals.
      The study herein demonstrates further growth of cholesterol into three
      dimensional crystals. We believe that these results may provide further insight
      into the formation of cholesterol crystals in early stages of atherosclerosis
      inflammation.

PMID- 22853904
TI  - Membrane-active peptides and the clustering of anionic lipids.
AB  - There is some overlap in the biological activities of cell-penetrating peptides
      (CPPs) and antimicrobial peptides (AMPs). We compared nine AMPs, seven CPPs, and
      a fusion peptide with regard to their ability to cluster anionic lipids in a
      mixture mimicking the cytoplasmic membrane of Gram-negative bacteria, as measured
      by differential scanning calorimetry. We also studied their bacteriostatic effect
      on several bacterial strains, and examined their conformational changes upon
      membrane binding using circular dichroism. A remarkable correlation was found
      between the net positive charge of the peptides and their capacity to induce
      anionic lipid clustering, which was independent of their secondary structure.
      Among the peptides studied, six AMPs and four CPPs were found to have strong
      anionic lipid clustering activity. These peptides also had bacteriostatic
      activity against several strains (particularly Gram-negative Escherichia coli)
      that are sensitive to lipid clustering agents. AMPs and CPPs that did not cluster
      anionic lipids were not toxic to E. coli. As shown previously for several types
      of AMPs, anionic lipid clustering likely contributes to the mechanism of
      antibacterial action of highly cationic CPPs. The same mechanism could explain
      the escape of CPPs from intracellular endosomes that are enriched with anionic
      lipids.

PMID- 22853905
TI  - Molecular cooperativity of drebrin1-300 binding and structural remodeling of F
      actin.
AB  - Drebrin A, an actin-binding protein, is a key regulatory element in synaptic
      plasticity of neuronal dendrites. Understanding how drebrin binds and remodels F
      actin is important for a functional analysis of their interactions.
      Conventionally, molecular models for protein-protein interactions use binding
      parameters derived from bulk solution measurements with limited spatial
      resolution, and the inherent assumption of homogeneous binding sites. In the case
      of actin filaments, their structural and dynamic states-as well as local changes
      in those states-may influence their binding parameters and interaction
      cooperativity. Here, we probed the structural remodeling of single actin
      filaments and the binding cooperativity of DrebrinA(1-300) -F-actin using AFM
      imaging. We show direct evidence of DrebrinA(1-300)-induced cooperative changes
      in the helical structure of F-actin and observe the binding cooperativity of
      drebrin to F-actin with nanometer resolution. The data confirm at the in vitro
      molecular level that variations in the F-actin helical structure can be modulated
      by cooperative binding of actin-binding proteins.

PMID- 22853906
TI  - Molecular and thermodynamic insights into the conformational transitions of
      Hsp90.
AB  - Hsp90, the most abundant cellular protein, has been implicated in numerous
      physiological and pathological processes. It controls protein folding and
      prevents aggregation, but it also plays a role in cancer and neurological
      disorders, making it an attractive drug target. Experimental efforts have
      demonstrated its remarkable structural flexibility and conformational complexity,
      which enable it to accommodate a variety of clients, but have not been able to
      provide a detailed molecular description of the conformational transitions. In
      our molecular dynamics simulations, Hsp90 underwent dramatic structural
      rearrangements into energetically favorable stretched and compact states. The
      transitions were guided by key electrostatic interactions between specific
      residues of opposite subunits. Nucleotide-bound structures showed the same
      conformational flexibility, although ADP and ATP seemed to potentiate these
      interactions by stabilizing two different closed conformations. Our observations
      may explain the difference in dynamic behavior observed among Hsp90 homologs, and
      the atomic resolution of the conformational transitions helps elucidate the
      complex chaperone machinery.

PMID- 22853907
TI  - The role of magnesium for geometry and charge in GTP hydrolysis, revealed by
      quantum mechanics/molecular mechanics simulations.
AB  - The coordination of the magnesium ion in proteins by triphosphates plays an
      important role in catalytic hydrolysis of GTP or ATP, either in signal
      transduction or energy conversion. For example, in Ras the magnesium ion
      contributes to the catalysis of GTP hydrolysis. The cleavage of GTP to GDP and
      P(i) in Ras switches off cellular signaling. We analyzed GTP hydrolysis in water,
      Ras, and Ras.Ras-GTPase-activating protein using quantum mechanics/molecular
      mechanics simulations. By comparison of the theoretical IR-difference spectra for
      magnesium ion coordinated triphosphate to experimental ones, the simulations are
      validated. We elucidated thereby how the magnesium ion contributes to catalysis.
      It provides a temporary storage for the electrons taken from the triphosphate and
      it returns them after bond cleavage and P(i) release back to the diphosphate.
      Furthermore, the Ras.Mg(2+) complex forces the triphosphate into a stretched
      conformation in which the beta- and gamma-phosphates are coordinated in a
      bidentate manner. In this conformation, the triphosphate elongates the bond,
      which has to be cleaved during hydrolysis. Furthermore, the gamma-phosphate
      adopts a more planar structure, driving the conformation of the molecule closer
      to the hydrolysis transition state. GTPase-activating protein enhances these
      changes in GTP conformation and charge distribution via the intruding arginine
      finger.

PMID- 22853908
TI  - Bovine beta-lactoglobulin is dimeric under imitative physiological conditions:
      dissociation equilibrium and rate constants over the pH range of 2.5-7.5.
AB  - The oligomerization of beta-lactoglobulin (betaLg) has been studied extensively,
      but with somewhat contradictory results. Using analytical ultracentrifugation in
      both sedimentation equilibrium and sedimentation velocity modes, we studied the
      oligomerization of betaLg variants A and B over a pH range of 2.5-7.5 in 100 mM
      NaCl at 25 degrees C. For the first time, to our knowledge, we were able to
      estimate rate constants (k(off)) for betaLg dimer dissociation. At pH 2.5 k(off)
      is low (0.008 and 0.009 s(-1)), but at higher pH (6.5 and 7.5) k(off) is
      considerably greater (>0.1 s(-1)). We analyzed the sedimentation velocity data
      using the van Holde-Weischet method, and the results were consistent with a
      monomer-dimer reversible self-association at pH 2.5, 3.5, 6.5, and 7.5. Dimer
      dissociation constants K(D)(2-1) fell close to or within the protein
      concentration range of ~5 to ~45 MUM, and at ~45 MUM the dimer predominated. No
      species larger than the dimer could be detected. The K(D)(2-1) increased as |pH
      pI| increased, indicating that the hydrophobic effect is the major factor
      stabilizing the dimer, and suggesting that, especially at low pH, electrostatic
      repulsion destabilizes the dimer. Therefore, through Poisson-Boltzmann
      calculations, we determined the electrostatic dimerization energy and the ionic
      charge distribution as a function of ionic strength at pH above (pH 7.5) and
      below (pH 2.5) the isoelectric point (pI~5.3). We propose a mechanism for dimer
      stabilization whereby the added ionic species screen and neutralize charges in
      the vicinity of the dimer interface. The electrostatic forces of the ion cloud
      surrounding betaLg play a key role in the thermodynamics and kinetics of dimer
      association/dissociation.

PMID- 22853909
TI  - What are the oxidation states of manganese required to catalyze photosynthetic
      water oxidation?
AB  - Photosynthetic O(2) production from water is catalyzed by a cluster of four
      manganese ions and a tyrosine residue that comprise the redox-active components
      of the water-oxidizing complex (WOC) of photosystem II (PSII) in all known
      oxygenic phototrophs. Knowledge of the oxidation states is indispensable for
      understanding the fundamental principles of catalysis by PSII and the catalytic
      mechanism of the WOC. Previous spectroscopic studies and redox titrations
      predicted the net oxidation state of the S(0) state to be (Mn(III))(3)Mn(IV). We
      have refined a previously developed photoassembly procedure that directly
      determines the number of oxidizing equivalents needed to assemble the Mn(4)Ca
      core of WOC during photoassembly, starting from free Mn(II) and the Mn-depleted
      apo-WOC complex. This experiment entails counting the number of light flashes
      required to produce the first O(2) molecules during photoassembly. Unlike
      spectroscopic methods, this process does not require reference to synthetic model
      complexes. We find the number of photoassembly intermediates required to reach
      the lowest oxidation state of the WOC, S(0), to be three, indicating a net
      oxidation state three equivalents above four Mn(II), formally (Mn(III))(3)Mn(II),
      whereas the O(2) releasing state, S(4), corresponds formally to
      (Mn(IV))(3)Mn(III). The results from this study have major implications for
      proposed mechanisms of photosynthetic water oxidation.

PMID- 22853910
TI  - Probing the elasticity of DNA on short length scales by modeling supercoiling
      under tension.
AB  - The wormlike-chain (WLC) model is widely used to describe the energetics of DNA
      bending. Motivated by recent experiments, alternative, so-called subelastic chain
      models were proposed that predict a lower elastic energy of highly bent DNA
      conformations. Until now, no unambiguous verification of these models has been
      obtained because probing the elasticity of DNA on short length scales remains
      challenging. Here we investigate the limits of the WLC model using coarse-grained
      Monte Carlo simulations to model the supercoiling of linear DNA molecules under
      tension. At a critical supercoiling density, the DNA extension decreases abruptly
      due to the sudden formation of a plectonemic structure. This buckling transition
      is caused by the large energy required to form the tightly bent end-loop of the
      plectoneme and should therefore provide a sensitive benchmark for model
      evaluation. Although simulations based on the WLC energetics could quantitatively
      reproduce the buckling measured in magnetic tweezers experiments, the buckling
      almost disappears for the tested linear subelastic chain model. Thus, our data
      support the validity of a harmonic bending potential even for small bending radii
      down to 3.5 nm.

PMID- 22853911
TI  - Mechanisms of SecM-mediated stalling in the ribosome.
AB  - Nascent-peptide modulation of translation is a common regulatory mechanism of
      gene expression. In this mechanism, while the nascent peptide is still in the
      exit tunnel of the ribosome, it induces translational pausing, thereby
      controlling the expression of downstream genes. One example is SecM, which
      inhibits peptide-bond formation in the ribosome's peptidyl transferase center
      (PTC) during its own translation, upregulating the expression of the protein
      translocase SecA. Although biochemical experiments and cryo-electron microscopy
      data have led to the identification of some residues involved in SecM
      recognition, the full pathway of interacting residues that connect SecM to the
      PTC through the ribosome has not yet been conclusively established. Here, using
      the cryo-electron microscopy data, we derived the first (to our knowledge) atomic
      model of the SecM-stalled ribosome via molecular-dynamics flexible fitting,
      complete with P- and A-site tRNAs. Subsequently, we carried out simulations of
      native and mutated SecM-stalled ribosomes to investigate possible interaction
      pathways between a critical SecM residue, R163, and the PTC. In particular, the
      simulations reveal the role of SecM in altering the position of the tRNAs in the
      ribosome, and thus demonstrate how the presence of SecM in the exit tunnel
      induces stalling. Finally, steered molecular-dynamics simulations in which SecM
      was pulled toward the tunnel exit suggest how SecA interacting with SecM from
      outside the ribosome relieves stalling.

PMID- 22853912
TI  - Insights from free-energy calculations: protein conformational equilibrium,
      driving forces, and ligand-binding modes.
AB  - Accurate free-energy calculations provide mechanistic insights into molecular
      recognition and conformational equilibrium. In this work, we performed free
      energy calculations to study the thermodynamic properties of different states of
      molecular systems in their equilibrium basin, and obtained accurate absolute
      binding free-energy calculations for protein-ligand binding using a newly
      developed M2 algorithm. We used a range of Asp-Phe-Gly (DFG)-in/out p38alpha
      mitogen-activated protein kinase inhibitors as our test cases. We also focused on
      the flexible DFG motif, which is closely connected to kinase activation and
      inhibitor binding. Our calculations explain the coexistence of DFG-in and DFG-out
      states of the loop and reveal different components (e.g., configurational entropy
      and enthalpy) that stabilize the apo p38alpha conformations. To study novel
      ligand-binding modes and the key driving forces behind them, we computed the
      absolute binding free energies of 30 p38alpha inhibitors, including analogs with
      unavailable experimental structures. The calculations revealed multiple stable,
      complex conformations and changes in p38alpha and inhibitor conformations, as
      well as balance in several energetic terms and configurational entropy loss. The
      results provide relevant physics that can aid in designing inhibitors and
      understanding protein conformational equilibrium. Our approach is fast for use
      with proteins that contain flexible regions for structure-based drug design.

PMID- 22853913
TI  - Trapping DNA near a solid-state nanopore.
AB  - We demonstrate that voltage-biased solid-state nanopores can transiently localize
      DNA in an electrolyte solution. A double-stranded DNA (dsDNA) molecule is trapped
      when the electric field near the nanopore attracts and immobilizes a non-end
      segment of the molecule across the nanopore orifice without inducing a folded
      molecule translocation. In this demonstration of the phenomenon, the ionic
      current through the nanopore decreases when the dsDNA molecule is trapped by the
      nanopore. By contrast, a translocating dsDNA molecule under the same conditions
      causes an ionic current increase. We also present finite-element modeling results
      that predict this behavior for the conditions of the experiment.

PMID- 22853914
TI  - Chemical composition and sulfur speciation in bulk tissue by x-ray spectroscopy
      and x-ray microscopy: corneal development during embryogenesis.
AB  - The chemical composition and sulfur (S) speciation of developing chick corneas at
      embryonic days 12, 14, and 16 were investigated using synchrotron scanning x-ray
      fluorescence microscopy and x-ray absorption near-edge structure spectroscopy.
      The aim was to develop techniques for the analysis of bulk tissue and identify
      critical physicochemical variations that correlate with changes in corneal
      structure-function relationships. Derived data were subjected to principal
      component analysis and linear discriminant analysis, which highlighted
      differences in the elemental and S species composition at different stages of
      embryonic growth. Notably, distinct elemental compositions of chlorine,
      potassium, calcium, phosphorus, and S altered with development during the
      transition of the immature opaque cornea to a mature transparent tissue. S
      structure spectroscopy revealed developmentally regulated alterations in thiols,
      organic monosulfides, ester sulfate, and inorganic sulfate species. The transient
      molecular structures and compositional changes reported here provide a deeper
      understanding of the underlying basis of corneal development during the
      acquisition of transparency. The experimental and analytical approach is new, to
      our knowledge, and has wide potential applicability in the life sciences.

PMID- 22853916
TI  - Determination of interaction kinetics between the T cell receptor and peptide
      loaded MHC class II via single-molecule diffusion measurements.
AB  - The binding of peptide-loaded major histocompatibility complex (pMHC) to the T
      cell receptor (TCR) represents the central step in T cell antigen recognition. It
      proceeds in the cell contact area between a T cell and an antigen-presenting cell
      termed the immunological synapse. An important and unresolved issue is how T
      cells discriminate between potentially harmful and harmless antigens. One
      limitation has been the difficulty to measure interaction parameters directly,
      that is, as they occur in the immunological synapse. Here we present a single
      molecule approach to determine pMHC-TCR interaction kinetics in situ based on
      diffusion analysis of dye-labeled pMHC. We find synaptic off-rates >10-fold
      accelerated when compared to the dissociation of purified proteins measured in
      vitro.

PMID- 22853915
TI  - Synchronization of early afterdepolarizations and arrhythmogenesis in
      heterogeneous cardiac tissue models.
AB  - Early afterdepolarizations (EADs) are linked to both triggered arrhythmias and
      reentrant arrhythmias by causing premature ventricular complexes (PVCs), focal
      excitations, or heterogeneous tissue substrates for reentry formation. However, a
      critical number of cells that synchronously exhibit EADs are needed to result in
      arrhythmia triggers and substrates in tissue. In this study, we use mathematical
      modeling and computer simulations to investigate EAD synchronization and
      arrhythmia induction in tissue models with random cell-to-cell variations. Our
      major observations are as follows. Random cell-to-cell variations in action
      potential duration without EAD presence do not cause large dispersion of
      refractoriness in well-coupled tissue. In the presence of phase-2 EADs, the cells
      may synchronously exhibit the same number of EADs or no EADs with a very small
      dispersion of refractoriness, or synchronize regionally to result in large
      dispersion of refractoriness. In the presence of phase-3 EADs, regional
      synchronization leads to propagating EADs, forming PVCs in tissue. Interestingly,
      even though the uncoupled cells exhibit either no EAD or only a single EAD, when
      these cells are coupled to form a tissue, more than one PVC can occur. When the
      PVCs occur at different locations and time, multifocal arrhythmias are triggered,
      with the foci shifting in space and time in an irregular manner. The focal
      arrhythmias either spontaneously terminate or degenerate into reentrant
      arrhythmias due to heterogeneities and spatiotemporal chaotic dynamics of the
      foci.

PMID- 22853917
TI  - Functional importance of short-range binding and long-range solvent interactions
      in helical antifreeze peptides.
AB  - Short-range ice binding and long-range solvent perturbation both have been
      implicated in the activity of antifreeze proteins and antifreeze glycoproteins.
      We study these two mechanisms for activity of winter flounder antifreeze peptide.
      Four mutants are characterized by freezing point hysteresis (activity), circular
      dichroism (secondary structure), Forster resonance energy transfer (end-to-end
      rigidity), molecular dynamics simulation (structure), and terahertz spectroscopy
      (long-range solvent perturbation). Our results show that the short-range model is
      sufficient to explain the activity of our mutants, but the long-range model
      provides a necessary condition for activity: the most active peptides in our data
      set all have an extended dynamical hydration shell. It appears that antifreeze
      proteins and antifreeze glycoproteins have reached different evolutionary
      solutions to the antifreeze problem, utilizing either a few precisely positioned
      OH groups or a large quantity of OH groups for ice binding, assisted by long
      range solvent perturbation.

PMID- 22853918
TI  - Elucidation of the mechanistic pathways of the hydroxyl radical scavenging
      reaction by daidzein using hybrid QM/MM dynamics.
AB  - Employing a hybrid QM/MM simulation we  explored the reaction dynamics of the
      hydroxyl radical scavenging activity of daidzein, a soy isoflavone. Our
      simulations illustrate that the highly reactive hydroxyl radical can participate
      in hydrogen abstraction reaction with both  OH functional groups of daidzein and
      can form stable daidzein radicals. We found that the reaction involving the 4'-OH
      site of daidzein is energetically favorable over the other reaction pathway
      involving the 7-OH site of daidzein by ~29 kcal/mol. The high enthalpic
      stabilization involved in  daidzein radical formation at the 4'-OH site can be
      partly attributed to better solvation through hydrogen-bonding interactions with
      water and higher electron density delocalization of radical over the adjacent
      aromatic ring. As evident from the QM/MM dynamics, both  HAT pathways led to 
      formation of ketones at the 7-OH and 4'-OH sites of daidzein, respectively, and
      the adjacent aromatic rings appear in a p-quinonoid form, a highly stable
      resonating structure. The suitability of the QM/MM methodology to study the
      reaction mechanism, identification of intermediate states, and pathways of
      flavonoid radical stabilization reported here opens up a new possibility to study
      a similar reaction mechanism in other systems.

PMID- 22853919
TI  - EMS response to an airliner crash.
AB  - This report of an aircraft crash at a major airport in Kingston, Jamaica examines
      the response of the local Emergency Medical Services (EMS). Factors that impacted
      the response are discussed, and the need for more disaster simulation exercises
      is highlighted. The objective of this case report was to document the response of
      EMS personnel to the crash of American Airlines Flight 331, and to utilize the
      information to examine and improve the present protocol. While multiple errors
      can occur during a mass-casualty event, these can be reduced by frequent
      simulation exercises during which various personnel practice and learn designated
      roles. Efficient triage, proper communication, and knowledge of the roles are
      important in ensuring the best possible outcome. While the triage system and
      response of the EMS personnel were effective for this magnitude of catastrophe,
      more work is needed in order to meet predetermined standards. Ways in which this
      can be overcome include: (1) hosting more disaster simulation exercises; (2)
      encouraging more involvement with first responders; and (3) strengthening the
      links in the local EMS system. Vigorous public education must be instituted and
      maintained.

PMID- 22853920
TI  - Causes of delivery and outcomes of very preterm twins stratified to zygosity.
AB  - The increasing rates of preterm birth among twins implicate that solid data on
      associated risks and outcomes are required. Assessment of zygosity is often based
      on clinical criteria (evaluation of placenta; same gender, birth weight
      discordance as surrogate criteria for monochorionic/monozygotic twins). The aim
      of this study was to compare clinical versus genetic assessment of zygosity and
      to compare causes of preterm delivery as well as outcome data of very-low-birth
      weight (VLBW; birth weight <1,500 g) twins stratified to zygosity. In a
      multicenter study, we selected n=176 sets of same gender twins and determined
      zygosity genetically. In a subgroup of 123 sets of twins, the attending
      physicians at the study centers were asked to document the parameter 'zygosity'
      (monozygotic/dizygotic) on the basis of their clinical judgment. Concordance
      between genetic and clinical assessment was 62.7% for monozygotic twins and 88.9%
      for dizygotic twins, respectively. Outcome parameters (death, BPD, ROP, NEC, IVH)
      were comparable in both groups. Genetically dizygotic twins were significantly
      more often born due to intrauterine infection (33% vs. 20% in monozygotic twins,
      p<.01) and antenatal antibiotics were more frequently given to mothers of
      dizygotic twins (62% vs. 47% in monozygotic twins, p<.01). Obstetric
      complications such as twin-twin-transfusion-syndrome were only seen in
      monozygotic twins as expected. The unexpected increase of antenatal antibiotic
      treatment and birth due to intrauterine infection in dizygotic twins should be
      confirmed in additional VLBW twin-cohorts.

PMID- 22853921
TI  - Coping profiles characterize individual flourishing, languishing, and depression.
AB  - According to the broaden-and-build theory of positive emotions, negative emotions
      narrow one's thought-action repertoire. In contrast, positive emotions have a
      broadening effect, expanding cognitive capacity, increasing potential coping
      strategies that come to mind, and enhancing decision-making, reaction, and
      adaptation to adversity. Fredrickson and Losada determined that a positivity
      ratio - the ratio of experienced positive to negative emotions - at or above 2.9
      promotes human flourishing. A ratio below 2.9 is indicative of languishing
      individuals, whereas a ratio below 1.0 is a marker of depression. This study
      examined whether adaptive and maladaptive coping profiles differentiated those
      who flourish, languish, or are depressed in two convenience samples - military
      spouses (n =367) and public school teachers (n=267). Results were consistent with
      the theoretical predictions, as coping profiles of the groups differed
      significantly, with flourishing individuals favoring adaptive coping strategies
      more than those who were languishing or depressed. Conversely, depressed
      individuals reported greater use of maladaptive coping strategies than those who
      were languishing or flourishing. These results provide further empirical support
      for the mathematical model of Fredrickson and Losada, as the set of positivity
      criteria were predictive of coping profiles in two samples where successful
      coping and adaptation are important.

PMID- 22853922
TI  - Preventing antibiotic resistance in the wild: a new end point for environmental
      risk assessment.

PMID- 22853923
TI  - Feline gastrointestinal microbiota.
AB  - The close relationship between gastrointestinal (GI) microbiota and its host has
      an impact on the health status of an animal that reaches beyond the GI tract. A
      balanced microbiome stimulates the immune system, aids in the competitive
      exclusion of transient pathogens and provides nutritional benefits to the host.
      With recent rapid advances in high-throughput sequencing technology, molecular
      approaches have become the routinely used tools for ecological studies of the
      feline microbiome, and have revealed a highly diverse and complex intestinal
      ecosystem in the feline GI tract. The major bacterial groups are similar to those
      found in other mammals, with Firmicutes, Bacteroidetes, Actinobacteria and
      Proteobacteria constituting more than 99% of intestinal microbiota. Several
      nutritional studies have demonstrated that the feline microbiota can be modulated
      by the amount of soluble fibers (i.e., prebiotics) and macronutrients (i.e.,
      protein content) in the diet. Initial clinical studies have suggested the
      presence of a dysbiosis in feline inflammatory bowel disease (IBD). Recently,
      metagenomic approaches have attempted to characterize the microbial gene pool.
      However, more studies are needed to describe the phylogenetic and functional
      changes in the intestinal microbiome in disease states and in response to
      environmental and dietary modulations. This paper reviews recent studies
      cataloging the microbial phylotypes in the GI tract of cats.

PMID- 22853924
TI  - Arsenic-induced interstitial myocardial fibrosis reveals a new insight into drug
      induced long QT syndrome.
AB  - AIMS: Arsenic trioxide (ATO), an effective therapeutic agent for acute
      promyelocytic leukaemia, can cause sudden cardiac death due to long QT syndrome
      (LQTS). The present study was designed to determine whether ATO could induce
      cardiac fibrosis and explore whether cardiac fibroblasts (CFs) are involved in
      the development of LQTS by ATO. METHODS AND RESULTS: ATO treatment of guinea pigs
      caused substantial interstitial myocardial fibrosis and LQTS, which was
      accompanied by an increase in transforming growth factor beta1(TGF-beta1)
      secretion and a decrease in ether-a-go-go-related gene (HERG) and inward
      rectifying potassium channel (I(K1)) subunit Kir2.1 protein levels. ATO promoted
      collagen production and TGF-beta1 expression and secretion in cultured CFs. Whole
      cell patch clamp and western blotting showed that treatment with TGF-beta1
      markedly reduced HERG and I(K1) current densities and downregulated HERG and
      Kir2.1 protein expression in HEK293 cells stably transfected with the human
      recombinant HERG channel and in cardiomyocytes (CMs). These changes were
      completely reversed by treatment with the protein kinase A (PKA) antagonist, H89.
      CM and CF co-cultures showed that ATO significantly increased TGF-beta1 levels in
      the culture medium, whereas markedly reduced HERG and Kir2.1 protein levels were
      observed in CMs compared with ATO-treated CMs not co-cultured with CFs. Finally,
      in vivo administration of LY364947, a pharmacological antagonist of TGF-beta
      signalling, dramatically prevented interstitial fibrosis and LQTS and abolished
      aberrant expression of TGF-beta1, HERG, and Kir2.1 in ATO-treated guinea pigs.
      CONCLUSION: ATO-induced TGF-beta1 secretion from CFs aggravates QT prolongation,
      suggesting that modulation of TGF-beta signalling may provide a novel strategy
      for the treatment of drug-induced LQTS.

PMID- 22853925
TI  - Current evidence on VEGF+405G/C polymorphism and malignancy susceptibility: a
      meta-analysis involving 30 studies.
AB  - The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor)
      polymorphism and malignancy susceptibility attracts considerable attention
      because VEGF is one of the most potent angiogenic factors and plays a critical
      role in the onset and development of malignancy. However, the published findings
      remain inconclusive. In order to derive a more precise assessment of the
      association, we performed a meta-analysis including 30 published case-control
      studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of the association.
      In the pooled analyses, no significant association was found between VEGF+405G/C
      polymorphism and malignancy susceptibility in different genetic models (G-allele
      vs. C-allele: OR=1.00, 95% CI: 0.93-1.07; CC vs. GG: OR=1.01, 95% CI: 0.88-1.15;
      GC+CC vs. GG: OR=1.00, 95% CI: 0.91-1.10; CC vs. GC+GG: OR=1.01, 95% CI: 0.90
      1.13). When stratified by ethnicity, a weak association between this polymorphism
      and malignancy susceptibility was found in African under allelic frequency
      comparison (OR=0.65, 95% CI: 0.43-0.98) and dominant genetic model comparison
      (OR=1.95, 95% CI: 1.09-3.50). In summary, although our meta-analysis indicated a
      weak association of VEGF+405G/C polymorphism with malignancy susceptibility in
      African, no persuasive evidence of association between the polymorphism and
      malignancy susceptibility was detected in the pooled analyses. Therefore, more
      studies with larger scale of participants, especially Africans, are required to
      further evaluate gene-environment interaction on this polymorphism and malignancy
      susceptibility.

PMID- 22853926
TI  - What a difference a day makes: examining the lag patterns of PM2.5 constituents.

PMID- 22853927
TI  - The intestinal microbiota in the rat model: major breakthroughs from new
      technologies.
AB  - The mammalian intestine harbors a large and diverse community of micro-organisms,
      known as the intestinal microbiota. Recent developments in molecular profiling
      methods, mainly based on microbial 16S ribosomal RNA gene sequencing, have
      provided unprecedented insights into the make-up and diversity of intestinal
      microbial communities. Using these culture-independent analyses, gut microbiota
      of several mammals including laboratory rodents, have been revisited. The
      laboratory rat is one of the major species bred and kept for scientific research.
      Although this animal is bred in confined environments and subjected to procedures
      for satisfying health requirements that hamper natural colonization, some major
      features of mammalian gut microbiota are conserved. However, the gut microbiota
      varies according to the breeding conditions of the rats and this could impact
      reproducibility of the experimental models. Determining the non-pathogenic
      microbial community might be relevant in standards of quality control of
      laboratory animals. Molecular profiling techniques could be applied to document
      this information.

PMID- 22853928
TI  - Dichorionic pregnancy: delayed interval delivery with endoloop ligation.
AB  - We describe two cases of delayed delivery in dichorionic, diamniotic pregnancies,
      where we used an Endoloop ligature to clamp the umbilical cord with excellent
      maternal and fetal long-term outcome.

PMID- 22853930
TI  - Novel stem cell-based drug discovery platforms for cardiovascular disease.
AB  - The complexity and diversity of many human diseases pose significant hurdles to
      the development of novel therapeutics. New scientific and technological advances,
      such as pharmacogenetics, provide valuable frameworks for understanding genetic
      predisposition to disease and tools for diagnosis and drug development. However,
      another framework is emerging based on recent scientific advances, one we suggest
      to call pharmacoempirics. Pharmacoempirics takes advantage of merging two nascent
      fields: first, the generation of induced pluripotent stem cells, which are
      differentiated into mature cell types and represent patient-specific genetic
      backgrounds, and, second, bioengineering advances allowing sophisticated re
      creation of human pathophysiology in laboratory settings. The combination of
      these two innovative technologies should allow new experimentation on disease
      biology and drug discovery, efficacy, and toxicology unencumbered by hypothesis
      generation and testing. In this review, we discuss the challenges and promises of
      this exciting new type of discovery platform and outline its implementation for
      cardiovascular drug discovery.

PMID- 22853929
TI  - Screening for inhibitors of an essential chromatin remodeler in mouse embryonic
      stem cells by monitoring transcriptional regulation.
AB  - The SWI/SNF-like adenosine triphosphate (ATP)-dependent chromatin remodeling
      complex, esBAF, is both necessary and, in some contexts, sufficient to induce the
      pluripotent state. Furthermore, mutations in various BAF subunits are associated
      with cancer. Little is known regarding the precise mechanism(s) by which this
      complex exerts its activities. Thus, it is unclear which protein interactions
      would be important to disrupt to isolate a relevant readout of mechanism. To
      address this, we developed a gene expression-based assay to identify inhibitors
      of the native esBAF complex. Specifically, a quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) assay was developed in mouse embryonic stem
      (ES) cells to monitor expression of Bmi1, a developmentally important gene
      repressed by the esBAF complex. The assay was miniaturized to a 384-well format
      and used to screen a diverse collection of compounds, including novel products of
      diversity-oriented synthesis (DOS). Confirmed hits were validated using a knock
      in ES cell reporter line in which luciferase is inserted into the Bmi1 locus.
      Several of the validated hits regulate a panel of target genes in a manner
      similar to the BAF chromatin-remodeling complex. Together these data indicate
      that expression-based screening using qRT-PCR is a successful approach to
      identify compounds targeting the regulation of key developmental genes in ES
      cells.

PMID- 22853931
TI  - Theoretical and experimental relationships between percent inhibition and IC50
      data observed in high-throughput screening.
AB  - The four-parameter logistic Hill equation models the theoretical relationship
      between inhibitor concentration and response and is used to derive IC(50) values
      as a measure of compound potency. This relationship is the basis for screening
      strategies that first measure percent inhibition at a single, uniform
      concentration and then determine IC(50) values for compounds above a threshold.
      In screening practice, however, a "good" correlation between percent inhibition
      values and IC(50) values is not always observed, and in the literature, there
      seems confusion about what correlation even to expect. We examined the
      relationship between percent inhibition data and IC(50) data in HDAC4 and ENPP2
      high-throughput screening (HTS) data sets and compared our findings with a series
      of numerical simulations that allowed the investigation of the influence of
      parameters representing different types of uncertainties: variability in the
      screening concentration (related to solution library and compound
      characteristics, liquid handling), variations in Hill model parameters (related
      to interaction of compounds with target, type of assay), and influences of assay
      data quality parameters (related to assay and experimental design, liquid
      handling). In the different sensitivity analyses, we found that the typical
      variations of the actual compound concentrations in existing screening libraries
      generate the largest contributions to imperfect correlations. Excess variability
      in the ENPP2 assay above the values of the simulation model can be explained by
      compound aggregation artifacts.

PMID- 22853932
TI  - Revised ethics guidelines for environmental epidemiologists.

PMID- 22853933
TI  - Real-time targeted molecular imaging using singular value spectra properties to
      isolate the adherent microbubble signal.
AB  - Ultrasound-based real-time molecular imaging in large blood vessels holds promise
      for early detection and diagnosis of various important and significant diseases,
      such as stroke, atherosclerosis, and cancer. Central to the success of this
      imaging technique is the isolation of ligand-receptor bound adherent microbubbles
      from free microbubbles and tissue structures. In this paper, we present a new
      approach, termed singular spectrum-based targeted molecular (SiSTM) imaging,
      which separates signal components using singular value spectra content over local
      regions of complex echo data. Simulations were performed to illustrate the
      effects of acoustic target motion and harmonic energy on SiSTM imaging-derived
      measurements of statistical dimensionality. In vitro flow phantom experiments
      were performed under physiologically realistic conditions (2.7 cm s-1 flow
      velocity and 4 mm diameter) with targeted and non-targeted phantom channels. Both
      simulation and experimental results demonstrated that the relative motion and
      harmonic characteristics of adherent microbubbles (i.e. low motion and large
      harmonics) yields echo data with a dimensionality that is distinct from free
      microbubbles (i.e. large motion and large harmonics) and tissue (i.e. low motion
      and low harmonics). Experimental SiSTM images produced the expected trend of a
      greater adherent microbubble signal in targeted versus non-targeted microbubble
      experiments (P < 0.05, n = 4). The location of adherent microbubbles was
      qualitatively confirmed via optical imaging of the fluorescent DiI signal along
      the phantom channel walls after SiSTM imaging. In comparison with two frequency
      based real-time molecular imaging strategies, SiSTM imaging provided
      significantly higher image contrast (P < 0.001, n = 4) and a larger area under
      the receiver operating characteristic curve (P < 0.05, n = 4).

PMID- 22853934
TI  - The intestinal microbiome of the pig.
AB  - The intestinal microbiome has been the subject of study for many decades because
      of its importance in the health and well being of animals. The bacterial
      components of the intestinal microbiome have closely evolved as animals have and
      in so doing contribute to the overall development and metabolic needs of the
      animal. The microbiome of the pig has been the subject of many investigations
      using culture-dependent methods and more recently using culture-independent
      techniques. A review of the literature is consistent with many of the ecologic
      principles put forth by Rene Dubos. Animals develop an intestinal microbiome over
      time and space. During the growth and development of the pig, the microbiome
      changes in composition in a process known as the microbial succession. There are
      clear and distinct differences in the composition of the pig intestinal
      microbiome moving from the proximal end of the intestinal tract to the distal
      end. The majority (>90%) of the bacteria in the pig intestinal microbiome are
      from two Phyla: Firmicutes and Bacteroidetes. However, the ileum has a high
      percentage of bacteria in the phylum Proteobacterium (up to 40%). Perturbations
      to the microbiome occur in response to many factors including stresses, treatment
      with antibiotics, and diet.

PMID- 22853936
TI  - NIEHS's new strategic plan.

PMID- 22853938
TI  - Comparative evaluation of support vector machine classification for computer
      aided detection of breast masses in mammography.
AB  - False positive (FP) marks represent an obstacle for effective use of computer
      aided detection (CADe) of breast masses in mammography. Typically, the problem
      can be approached either by developing more discriminative features or by
      employing different classifier designs. In this paper, the usage of support
      vector machine (SVM) classification for FP reduction in CADe is investigated,
      presenting a systematic quantitative evaluation against neural networks, k
      nearest neighbor classification, linear discriminant analysis and random forests.
      A large database of 2516 film mammography examinations and 73 input features was
      used to train the classifiers and evaluate for their performance on correctly
      diagnosed exams as well as false negatives. Further, classifier robustness was
      investigated using varying training data and feature sets as input. The
      evaluation was based on the mean exam sensitivity in 0.05-1 FPs on normals on the
      free-response receiver operating characteristic curve (FROC), incorporated into a
      tenfold cross validation framework. It was found that SVM classification using a
      Gaussian kernel offered significantly increased detection performance (P =
      0.0002) compared to the reference methods. Varying training data and input
      features, SVMs showed improved exploitation of large feature sets. It is
      concluded that with the SVM-based CADe a significant reduction of FPs is possible
      outperforming other state-of-the-art approaches for breast mass CADe.

PMID- 22853939
TI  - Improvement of anti-TNFalpha antibody-induced pustular psoriasis by azathioprine.

PMID- 22853940
TI  - Commensal microbiome effects on mucosal immune system development in the ruminant
      gastrointestinal tract.
AB  - Commensal microflora play many roles within the mammalian gastrointestinal tract
      (GIT) that benefit host physiology by way of direct or indirect interactions with
      mucosal surfaces. Commensal flora comprises members across all microbial phyla,
      although predominantly bacterial, with population dynamics varying with host
      species, genotype, and environmental factors. Little is known, however, about the
      complex mechanisms regulating host-commensal interactions that underlie this
      mutually beneficial relationship and how alterations in the microbiome may
      influence host development and susceptibility to infection. Research into the gut
      microbiome has intensified as it becomes increasingly evident that symbiont-host
      interactions have a significant impact on mucosal immunity and health.
      Furthermore, evidence that microbial populations vary significantly throughout
      the GIT suggest that regional differences in the microbiome may also influence
      immune function within distinct compartments of the GIT. Postpartum colonization
      of the GIT has been shown to have a direct effect on mucosal immune system
      development, but information is limited regarding regional effects of the
      microbiome on the development, activation, and maturation of the mucosal immune
      system. This review discusses factors influencing the colonization and
      establishment of the microbiome throughout the GIT of newborn calves and the
      evidence that regional differences in the microbiome influence mucosal immune
      system development and maturation. The implications of this complex interaction
      are also discussed in terms of possible effects on responses to enteric pathogens
      and vaccines.

PMID- 22853941
TI  - Dynamic stability control in younger and older adults during stair descent.
AB  - The purpose of this study was to examine dynamic stability control in older and
      younger adults while descending stairs. Thirteen older (aged 64-77 years) and 13
      younger (aged 22-29 years) adults descended a staircase at their preferred speed.
      A motion capture system and three force plates were used to determine locomotion
      mechanics. Dynamic stability was investigated by using the margin of stability,
      calculated as the instantaneous difference between anterior boundary of the base
      of support and extrapolated centre of mass. At the initiation of the single
      support phase, older adults demonstrated a more negative (p<.05) margin of
      stability value. The component responsible for the lower margin of stability in
      the elderly was the higher velocity of the centre of mass (p<.05). Before the
      initiation of the single support phase, the older adults showed a lower (p<.05)
      ankle and knee joint angular impulse compared to the younger ones. We found a
      significant correlation (r=.729, p<.05) between centre of mass velocity and joint
      angular impulse. These results indicate that older adults are at greater risk of
      falls while descending stairs potentially due to a reduced ability to generate
      adequate leg-extensor muscular output to safely control the motion of the body's
      centre of mass while stepping down.

PMID- 22853943
TI  - Introduction to the series of papers on animal microbiomes.

PMID- 22853942
TI  - Cusp height in aortic valves.
AB  - OBJECTIVES: Successful aortic valve repair must normalize cusp and root
      dimensions. Limited information is available on the normal dimensions of human
      cusps, in particular the cusp height. METHODS: The cusp height was measured
      intraoperatively in 621 patients during aortic valve repair procedures. A
      tricuspid anatomy was present in 329 patients and bicuspid in 286 patients. In
      addition, patient age, gender, height, weight, preoperative degree of aortic
      regurgitation, and aortic dimensions were recorded. The data were analyzed for
      possible interrelation between the cusp height and clinical variables. RESULTS:
      In the bicuspid valves, the geometric height of the nonfused cusp ranged from 15
      to 30 mm (mean, 23.8 +/- 2.0). Significant correlations were found between the
      cusp height and all clinical variables. In the tricuspid valves, the height of
      the noncoronary cusp ranged from 14 to 28 mm (mean, 20.7 +/- 2.2). The height of
      the left coronary cusp varied from 12 to 25 mm (mean, 20.0 +/- 2.1) and that of
      the right coronary cusp from 12 to 25 mm (mean, 20.0 +/- 2.1). The noncoronary
      cusp was significantly greater than the left and the right coronary cusp (P =
      .000). No difference was found between the left and right cusps (P = .513).
      Significant correlations between the geometric height and clinical parameters
      were found for most clinical variables, excluding the degree of aortic
      regurgitation. CONCLUSIONS: We found the cusp height was larger than previously
      published. It shows marked variability and correlates with the clinical
      variables. These data might serve as the basis for decision making in aortic
      valve repair.

PMID- 22853944
TI  - High throughput sequencing methods for microbiome profiling: application to food
      animal systems.
AB  - Analysis of microbial communities using high throughput sequencing methods began
      in the mid 2000s permitting the production of 1000s to 10,000s of sequence reads
      per sample and megabases of data per sequence run. This then unprecedented depth
      of sequencing allowed, for the first time, the discovery of the 'rare biosphere'
      in environmental samples. The technology was quickly applied to studies in
      several human subjects. Perhaps these early studies served as a reminder that
      though the microbes that inhabit mammals are known to outnumber host cells by an
      order of magnitude or more, most of these are unknown members of our second
      genome, or microbiome (as coined by Joshua Lederberg), because of our inability
      to culture them. High throughput methods for microbial 16S ribosomal RNA gene and
      whole genome shotgun (WGS) sequencing have now begun to reveal the composition
      and identity of archaeal, bacterial and viral communities at many sites, in and
      on the human body. Surveys of the microbiota of food production animals have been
      published in the past few years and future studies should benefit from protocols
      and tools developed from large-scale human microbiome studies. Nevertheless,
      production animal-related resources, such as improved host genome assemblies and
      increased numbers and diversity of host-specific microbial reference genome
      sequences, will be needed to permit meaningful and robust analysis of 16S rDNA
      and WGS sequence data.

PMID- 22853945
TI  - The microbiome of the chicken gastrointestinal tract.
AB  - The modern molecular biology movement was developed in the 1960s with the
      conglomeration of biology, chemistry, and physics. Today, molecular biology is an
      integral part of studies aimed at understanding the evolution and ecology of
      gastrointestinal microbial communities. Molecular techniques have led to
      significant gains in our understanding of the chicken gastrointestinal
      microbiome. New advances, primarily in DNA sequencing technologies, have equipped
      researchers with the ability to explore these communities at an unprecedented
      level. A reinvigorated movement in systems biology offers a renewed promise in
      obtaining a more complete understanding of chicken gastrointestinal microbiome
      dynamics and their contributions to increasing productivity, food value,
      security, and safety as well as reducing the public health impact of raising
      production animals. Here, we contextualize the contributions molecular biology
      has already made to our understanding of the chicken gastrointestinal microbiome
      and propose targeted research directions that could further exploit molecular
      technologies to improve the economy of the poultry industry.

PMID- 22853946
TI  - The microbiome of the soft palate of swine.
AB  - The tonsil of the soft palate in pigs is a secondary lymphoid tissue that
      provides a first line of defense against foreign antigens entering by the mouth
      or nares. It has been known for a long time to be the site of colonization of
      important swine and zoonotic bacterial pathogens. Initially our understanding of
      microbes present at this site came from culture-based studies. Very recently,
      sequence-based approaches have been used to identify the core microbiome of the
      swine tonsil. Although animal to animal and herd to herd variation was detected
      in these studies, >90 of the organisms detected belonged to the phyla
      Proteobacteria and Firmicutes. Members of the family Pasteurellaceae appeared to
      be predominate in the tonsil; however, the relative proportions of
      Actinobacillus, Haemophilus, and Pasteurella varied. Members of the families
      Moraxellaceae, Fusobacteriaceae, Veillonellaceae, and Neisseriaceae were also
      seen as frequent residents of the tonsil.

PMID- 22853948
TI  - Reflection of Lamb waves obliquely incident on the free edge of a plate.
AB  - The reflection of obliquely incident symmetric and anti-symmetric Lamb wave modes
      at the edge of a plate is studied. Both in-plane and Shear-Horizontal (SH)
      reflected wave modes are spawned by an obliquely incident in-plane Lamb wave
      mode. Energy reflection coefficients are calculated for the reflected wave modes
      as a function of frequency and angle of incidence. This is done by using the
      method of orthogonal mode decomposition and by enforcing traction free conditions
      at the plate edge using the method of collocation. A PZT sensor network, affixed
      to an Aluminum plate, is used to experimentally verify the predictions of the
      analysis. Experimental results provide support for the analytically determined
      results.

PMID- 22853949
TI  - Target detection in diagnostic ultrasound: Evaluation of a method based on the
      CLEAN algorithm.
AB  - A technique is proposed for the detection of abnormalities (targets) in
      ultrasound images using little or no a priori information and requiring little
      operator intervention. The scheme is a combination of the CLEAN algorithm,
      originally proposed for radio astronomy, and constant false alarm rate (CFAR)
      processing, as developed for use in radar systems. The CLEAN algorithm identifies
      areas in the ultrasound image that stand out above a threshold in relation to the
      background; CFAR techniques allow for an adaptive, semi-automated, selection of
      the threshold. Neither appears to have been previously used for target detection
      in ultrasound images and never together in any context. As a first step towards
      assessing the potential of this method we used a widely used method of simulating
      B-mode images (Field II). We assumed the use of a 256 element linear array
      operating at 3.0MHz into a water-like medium containing a density of point
      scatterers sufficient to simulate a background of fully developed speckle.
      Spherical targets with diameters ranging from 0.25 to 6.0mm and contrasts ranging
      from 0 to 12dB relative to the background were used as test objects. Using a
      contrast-detail analysis, the probability of detection curves indicate these
      targets can be consistently detected within a speckle background. Our results
      indicate that the method has considerable promise for the semi-automated
      detection of abnormalities with diameters greater than a few millimeters,
      depending on the contrast.

PMID- 22853950
TI  - Self-surface assembly of cellulosomes with two miniscaffoldins on Saccharomyces
      cerevisiae for cellulosic ethanol production.
AB  - Yeast to directly convert cellulose and, especially, the microcrystalline
      cellulose into bioethanol, was engineered through display of minicellulosomes on
      the cell surface of Saccharomyces cerevisiae. The construction and cell surface
      attachment of cellulosomes were accomplished with two individual miniscaffoldins
      to increase the display level. All of the cellulases including a celCCA
      (endoglucanase), a celCCE (cellobiohydrolase), and a Ccel_2454 (beta-glucosidase)
      were cloned from Clostridium cellulolyticum, ensuring the thermal compatibility
      between cellulose hydrolysis and yeast fermentation. Cellulases and one of
      miniscaffoldins were secreted by alpha-factor; thus, the assembly and attachment
      to anchoring miniscaffoldin were accomplished extracellularly. Immunofluorescence
      microscopy, flow cytometric analysis (FACS), and cellulosic ethanol fermentation
      confirmed the successful display of such complex on the yeast surface. Enzyme
      enzyme synergy, enzyme-proximity synergy, and cellulose-enzyme-cell synergy were
      analyzed, and the length of anchoring miniscaffoldin was optimized. The
      engineered S. cerevisiae was applied in fermentation of carboxymethyl cellulose
      (CMC), phosphoric acid-swollen cellulose (PASC), or Avicel. It showed a
      significant hydrolytic activity toward microcrystalline cellulose, with an
      ethanol titer of 1,412 mg/L. This indicates that simultaneous saccharification
      and fermentation of crystalline cellulose to ethanol can be accomplished by the
      yeast, engineered with minicellulosome.

PMID- 22853951
TI  - Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination
      facilitates estrogen receptor alpha target gene activation.
AB  - Cofactors for estrogen receptor alpha (ERalpha) can modulate gene activity by
      posttranslationally modifying histone tails at target promoters. Here, we found
      that stimulation of ERalpha-positive cells with 17beta-estradiol (E2) promotes
      global citrullination of histone H3 arginine 26 (H3R26) on chromatin.
      Additionally, we found that the H3 citrulline 26 (H3Cit26) modification
      colocalizes with ERalpha at decondensed chromatin loci surrounding the estrogen
      response elements of target promoters. Surprisingly, we also found that
      citrullination of H3R26 is catalyzed by peptidylarginine deiminase (PAD) 2 and
      not by PAD4 (which citrullinates H4R3). Further, we showed that PAD2 interacts
      with ERalpha after E2 stimulation and that inhibition of either PAD2 or ERalpha
      strongly suppresses E2-induced H3R26 citrullination and ERalpha recruitment at
      target gene promoters. Collectively, our data suggest that E2 stimulation induces
      the recruitment of PAD2 to target promoters by ERalpha, whereby PAD2 then
      citrullinates H3R26, which leads to local chromatin decondensation and
      transcriptional activation.

PMID- 22853952
TI  - A microRNA network regulates expression and biosynthesis of wild-type and
      DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
AB  - Production of functional proteins requires multiple steps, including gene
      transcription and posttranslational processing. MicroRNAs (miRNAs) can regulate
      individual stages of these processes. Despite the importance of the cystic
      fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion
      transport, how its expression is regulated remains uncertain. We discovered that
      miRNA-138 regulates CFTR expression through its interactions with the
      transcriptional regulatory protein SIN3A. Treating airway epithelia with an miR
      138 mimic increased CFTR mRNA and also enhanced CFTR abundance and
      transepithelial Cl(-) permeability independent of elevated mRNA levels. An miR
      138 anti-miR had the opposite effects. Importantly, miR-138 altered the
      expression of many genes encoding proteins that associate with CFTR and may
      influence its biosynthesis. The most common CFTR mutation, DeltaF508, causes
      protein misfolding, protein degradation, and cystic fibrosis. Remarkably,
      manipulating the miR-138 regulatory network also improved biosynthesis of CFTR
      DeltaF508 and restored Cl(-) transport to cystic fibrosis airway epithelia. This
      miRNA-regulated network directs gene expression from the chromosome to the cell
      membrane, indicating that an individual miRNA can control a cellular process more
      broadly than recognized previously. This discovery also provides therapeutic
      avenues for restoring CFTR function to cells affected by the most common cystic
      fibrosis mutation.

PMID- 22853953
TI  - Detection of ultra-rare mutations by next-generation sequencing.
AB  - Next-generation DNA sequencing promises to revolutionize clinical medicine and
      basic research. However, while this technology has the capacity to generate
      hundreds of billions of nucleotides of DNA sequence in a single experiment, the
      error rate of ~1% results in hundreds of millions of sequencing mistakes. These
      scattered errors can be tolerated in some applications but become extremely
      problematic when "deep sequencing" genetically heterogeneous mixtures, such as
      tumors or mixed microbial populations. To overcome limitations in sequencing
      accuracy, we have developed a method termed Duplex Sequencing. This approach
      greatly reduces errors by independently tagging and sequencing each of the two
      strands of a DNA duplex. As the two strands are complementary, true mutations are
      found at the same position in both strands. In contrast, PCR or sequencing errors
      result in mutations in only one strand and can thus be discounted as technical
      error. We determine that Duplex Sequencing has a theoretical background error
      rate of less than one artifactual mutation per billion nucleotides sequenced. In
      addition, we establish that detection of mutations present in only one of the two
      strands of duplex DNA can be used to identify sites of DNA damage. We apply the
      method to directly assess the frequency and pattern of random mutations in
      mitochondrial DNA from human cells.

PMID- 22853954
TI  - Loss of deeply conserved C-class floral homeotic gene function and C- and E-class
      protein interaction in a double-flowered ranunculid mutant.
AB  - In the model plant Arabidopsis thaliana, a core eudicot, the floral homeotic C
      class gene AGAMOUS (AG) has a dual role specifying reproductive organ identity
      and floral meristem determinacy. We conduct a functional analysis of the putative
      AG ortholog ThtAG1 from the ranunculid Thalictrum thalictroides, a representative
      of the sister lineage to all other eudicots. Down-regulation of ThtAG1 by virus
      induced gene silencing resulted in homeotic conversion of stamens and carpels
      into sepaloid organs and loss of flower determinacy. Moreover, flowers exhibiting
      strong silencing of ThtAG1 phenocopied the double-flower ornamental cultivar T.
      thalictroides 'Double White.' Molecular analysis of 'Double White' ThtAG1 alleles
      revealed the insertion of a retrotransposon causing either nonsense-mediated
      decay of transcripts or alternative splicing that results in mutant proteins with
      K-domain deletions. Biochemical analysis demonstrated that the mutation abolishes
      protein-protein interactions with the putative E-class protein ThtSEP3. C- and E
      class protein heterodimerization is predicted by the floral quartet model, but
      evidence for the functional importance of this interaction is scarce outside the
      core eudicots. Our findings therefore corroborate the importance and conservation
      of the interactions between C- and E-class proteins. This study provides a
      functional description of a full C-class mutant in a noncore ("basal") eudicot,
      an ornamental double flower, affecting both organ identity and meristem
      determinacy. Using complementary forward and reverse genetic approaches, this
      study demonstrates deep conservation of the dual C-class gene function and of the
      interactions between C- and E-class proteins predicted by the floral quartet
      model.

PMID- 22853955
TI  - Coxsackievirus B3 mutator strains are attenuated in vivo.
AB  - Based on structural data of the RNA-dependent RNA polymerase, rational targeting
      of key residues, and screens for Coxsackievirus B3 fidelity variants, we isolated
      nine polymerase variants with mutator phenotypes, which allowed us to probe the
      effects of lowering fidelity on virus replication, mutability, and in vivo
      fitness. These mutator strains generate higher mutation frequencies than WT virus
      and are more sensitive to mutagenic treatments, and their purified polymerases
      present lower-fidelity profiles in an in vitro incorporation assay. Whereas these
      strains replicate with WT-like kinetics in tissue culture, in vivo infections
      reveal a strong correlation between mutation frequency and fitness. Variants with
      the highest mutation frequencies are less fit in vivo and fail to productively
      infect important target organs, such as the heart or pancreas. Furthermore,
      whereas WT virus is readily detectable in target organs 30 d after infection,
      some variants fail to successfully establish persistent infections. Our results
      show that, although mutator strains are sufficiently fit when grown in large
      population size, their fitness is greatly impacted when subjected to severe
      bottlenecking, which would occur during in vivo infection. The data indicate
      that, although RNA viruses have extreme mutation frequencies to maximize
      adaptability, nature has fine-tuned replication fidelity. Our work forges ground
      in showing that the mutability of RNA viruses does have an upper limit, where
      larger than natural genetic diversity is deleterious to virus survival.

PMID- 22853957
TI  - Is the psychosocial profile of people with low back pain seeking care in Danish
      primary care different from those in secondary care?
AB  - Differences between the psychosocial risk factors of low back pain (LBP) patients
      in primary and secondary care are under-investigated. Similarly, differences in
      the psychosocial profile of people classified into STarT Back Screening Tool
      (SBT) subgroups in primary and secondary care settings have not been
      investigated. The aim of the study was to determine: (1) if movement-related
      fear, catastrophisation, anxiety and/or depression in LBP patients are different
      between primary and secondary care settings, and (2) if those differences are
      retained when stratified by SBT subgroup. This study was a cross-sectional
      comparison of LBP patients in Danish primary settings (405 general practitioner
      or physiotherapy patients) and a secondary care setting (311 outpatient spine
      centre patients). Psychosocial factors were measured with the Roland Morris
      Disability Questionnaire, the Tampa Scale of Kinesiophobia, the Coping Strategies
      Questionnaire (catastrophisation subscale), and the Hospital Anxiety and
      Depression Scale. There were significantly higher scores in secondary care for
      movement-related fear (1.3 points (95%CI .1-2.5) p = .030) and catastrophisation
      (2.0 (95%CI 1.0-3.0) p < .000), lower scores on anxiety (-1.0 (95%CI -1.0-2.0) p
      < .000) but no difference for depression. These differences in psychosocial
      scores were broadly retained when stratified by SBT subgroup. However,
      questionnaire-specific reported thresholds for important difference scores
      indicate the size of these differences between the care settings were unlikely to
      be clinically important from a patient perspective. Longitudinal studies are
      required to investigate the predictive ability of SBT in secondary care settings
      and whether treatment targeted to SBT subgroups is effective in secondary care.

PMID- 22853956
TI  - Checkpoint kinase 2 (Chk2) inhibits the activity of the Cdc45/MCM2-7/GINS (CMG)
      replicative helicase complex.
AB  - The replication of eukaryote chromosomes slows down when DNA is damaged and the
      proteins that work at the fork (the replisome) are known targets for the
      signaling pathways that mediate such responses critical for accurate genomic
      inheritance. However, the molecular mechanisms and details of how this response
      is mediated are poorly understood. In this report we show that the activity of
      replisome helicase, the Cdc45/MCM2-7/GINS (CMG) complex, can be inhibited by
      protein phosphorylation. Recombinant Drosophila melanogaster CMG can be
      stimulated by treatment with phosphatase whereas Chk2 but not Chk1 interferes
      with the helicase activity in vitro. The targets for Chk2 phosphorylation have
      been identified and reside in MCM subunits 3 and 4 and in the GINS protein Psf2.
      Interference requires a combination of modifications and we suggest that the
      formation of negative charges might create a surface on the helicase to
      allosterically affect its function. The treatment of developing fly embryos with
      ionizing radiation leads to hyperphosphorylation of Psf2 subunit in the active
      helicase complex. Taken together these data suggest that the direct modification
      of the CMG helicase by Chk2 is an important nexus for response to DNA damage.

PMID- 22853958
TI  - Lack of high-quality evidence on the value of sentinel node biopsy in melanoma.

PMID- 22853959
TI  - Dermoscopy of early dissecting cellulitis of the scalp simulates alopecia areata.

PMID- 22853960
TI  - Oral propranolol for treating infantile hemangiomas: a case series of 57
      patients.
AB  - INTRODUCTION AND OBJECTIVES: Infantile hemangiomas (IH) are a frequent vascular
      tumor. In recent years, propranolol has emerged as an alternative in the
      treatment of IH. The objective of the present study was to evaluate the
      effectiveness of propranolol for the treatment of IH. MATERIALS AND METHODS:
      Patients with IH requiring treatment were included. Cardiologic evaluation was
      made to every patient and electrocardiogram (ECG) and echocardiogram were done.
      Oral propranolol was started in an ambulatory way at a dose of 2mg/kg daily
      divided in two doses. At ten days all the patients were evaluated with a 24-h
      rhythm holter. Evaluation of effectiveness: In clinical controls and by images IH
      were formally analyzed, without blindness. Response was categorized as complete
      response (CR), partial response (PR) and no response (NR). Adverse events:
      Adverse events were registered in a special category of the formulary. RESULTS:
      57 patients were included. Mean age was 9.7 months. There were 80.8% females.
      Mean duration of treatment was 7.3 months (1-24 months). EFFICACY: 50.6% had CR,
      49.3% had PR. There were a 7% of adverse events. No differences in response rate
      exist according to age or location. No rhythm holter was altered at ten-day
      control. CONCLUSION: Our study highlights the possibility of starting propranolol
      in an ambulatory way, establishes a dose of 2mg/kg/day and confirms the security
      profile of the drug. We consider propranolol as a first line treatment for IH.

PMID- 22853962
TI  - Cutaneous metastases of internal tumors.
AB  - Cutaneous metastases are relatively rare in clinical practice and their diagnosis
      requires a high index of suspicion because clinical findings can be subtle. These
      metastases reveal the presence of disseminated malignant disease and can lead to
      the diagnosis of unsuspected internal tumors or the spread or recurrence of an
      already diagnosed tumor. Early recognition of cutaneous metastases can facilitate
      prompt and accurate diagnosis resulting in early treatment; however, they are
      generally indicative of a poor prognosis. Some tumors have a predilection to
      metastasize to specific areas. Recognition of these patterns provides essential
      information that can guide the search for the underlying tumor. 

PMID- 22853963
TI  - Large asymmetric pigmented nodule in a 27-year-old female.

PMID- 22853964
TI  - Phase-contrast x-ray imaging and tomography of the nematode Caenorhabditis
      elegans.
AB  - We have analyzed the model organism Caenorhabditis elegans with the help of phase
      contrast x-ray tomography. This work combines techniques from x-ray imaging
      studies of single biological cells by in-line holography with three-dimensional
      reconstruction and furthermore extends these studies to the multicellular level.
      To preserve the sub-cellular ultrastructure of the nematodes, we used the near
      native sample preparation of high-pressure freezing as commonly used in the field
      of electron microscopy. For the presented samples, a standard, non-magnifying
      parallel-beam setting, as well as a magnifying, divergent-beam setting using
      nanofocusing optics is evaluated based on their tomographic reconstruction
      potential. In this paper, we address difficulties in sample preparation and
      issues of image processing. By experimental refinement and through optimized
      reconstruction procedures, we were able to perform x-ray imaging studies on a
      living specimen.

PMID- 22853965
TI  - Automated mass spectrometry-based functional assay for the routine analysis of
      the secretome.
AB  - The secretome represents the set of proteins secreted into the extracellular
      space of cells. These proteins have been shown to play a major role in cell-cell
      communication. For example, recent observations revealed the presence of
      diffusible factors with proliferative properties in the secretome of cancer
      cells. Thus, a qualitative and quantitative analysis of the secretome could lead
      to the identification of these factors and consequently to the development of new
      therapeutic strategies. Here, we provide an automated simple and effective
      strategy to identify novel targets in the secretome of specifically treated cells
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, we
      explore the supportive role of mass spectrometry (MS) in the development of
      functional assays of identified secreted target molecules. Simplicity is achieved
      by growing cells in medium free of serum, which eliminates the need to remove the
      most abundant serum proteins and at the same time reduces disturbing matrix
      effects. Upon identification of these factors, their validation and
      characterization will follow. Moreover, this approach can also lead to the
      identification of proteins abnormally secreted, shed, or oversecreted by cells as
      response to a stimulus. Furthermore, we also discuss the problems that one may
      encounter. Finally, we discuss the broad application of automated MS-based
      proteomics, particularly in cancer research, highlighting new horizons for the
      use of MS.

PMID- 22853966
TI  - Ultrasound-guided injection in osteoarticular pathologies: general principles and
      precautions.
AB  - In the past, needle aspirations or injections involving the motor system were
      always carried out either blind or guided by fluoroscopy. Over the last few
      years, sonography has begun to offer an interesting alternative. Its advantages
      are that it is a relatively inexpensive technique, while not emitting ionising
      radiation and being easily accessible. There has been a great deal of technical
      progress including high frequency transducers, which have led to performance
      improvements in terms of both diagnosis and treatment of pathologies of the motor
      system. Due to these technical advances and to sterile covers for the
      transducers, it is now possible to visualise and to aspirate or inject into a
      peripheral joint, a tendon sheath or a bursa with or without effusion. This
      technique does not require a contrast medium injection because the needle
      position can be checked directly. Minimally invasive, it allows a number of
      interventions to be carried out with a very low complication rate since the
      entire path of the needle is followed using sonography, which means that nerves,
      vessels and other structures can be avoided because they are visualised directly
      in real time.

PMID- 22853967
TI  - Preferential technological and life cycle environmental performance of chitosan
      flocculation for harvesting of the green algae Neochloris oleoabundans.
AB  - Dewatering of the green algae Neochloris oleoabundans by flocculation was
      investigated for chitosan biopolymer, ferric sulfate, and alum. Chitosan was
      found to be most effective flocculant, with an optimum dose of 100mg/L algae
      broth. Zeta potential measurements suggest the mechanism involves both adsorption
      and charge neutralization processes. Life cycle assessment (LCA) was used to
      compare the chitosan method to other flocculation methods as well as
      centrifugation and filtration/chamber press processes. LCA showed that among
      these techniques, flocculation by chitosan is the least energy intensive and had
      the lowest impacts across all other categories of environmental impacts. The
      results are discussed in the overall context of biofuel production from algal
      biomass.

PMID- 22853968
TI  - Review on the fate of emerging contaminants during sludge anaerobic digestion.
AB  - Several research papers have been published during the last years investigating
      the occurrence, fate and effects of emerging contaminants (ECs) on sludge
      anaerobic digestion (AD). Literature review revealed that research has been
      mainly focused on specific groups of compounds (linear alkylbenzene sulphonates,
      nonylphenol ethoxylates, some pharmaceuticals, estrogens, phthalates), while
      there are fewer or no data for others (personal care products, perfluorinated
      compounds, brominated flame retardants, organotins, benzotriazoles,
      benzothiazoles, nanoparticles). AD operational parameters (sludge residence time,
      temperature), sludge characteristics (type of sludge, adaptation on the
      compound), physicochemical properties of ECs and co-metabolic phenomena seem to
      affect compounds' biodegradation. The use of sludge pretreatment methods does not
      seem to enhance ECs removal; whereas encouraging results have been reported when
      AD was combined with other treatment methods. Future efforts should be focused on
      better understanding of biotransformation processes and sorption phenomena
      occurred in anaerobic digesters, as well as on identification of
      (bio)transformation products.

PMID- 22853969
TI  - Electrical burn is still a major risk factor for amputations.
AB  - Many difficult decisions are faced in the early management of severely burned
      patient. The decision to amputate an extremity or extremities may be very
      difficult but reduce morbidity and enhance survival of the patient. In a total of
      1144 patients from January 2000 and June 2011, there were 44 patients (3.8%)
      undergoing amputations of the digits or upper extremity proximal to the wrist or
      lower extremity above the ankle. Amputations were significantly higher in males
      and the mean hospitalization time was also significantly higher in these
      patients. Majority of the patients had non-viable tissue (79.5%) and nine
      patients (20.5%) had a septic focus as cause of amputation. The majority of
      amputations were caused by high-voltage electrical injury. Education and
      compliance with safety measures, as well as common sense and respect for the
      potential danger of electricity, are still essential for avoiding these injuries.

PMID- 22853970
TI  - An effective antioxidant drug on prevention of the necrosis of zone of stasis: N
      acetylcysteine.
AB  - The zone of stasis, the encircling area of the zone of coagulation, is a critical
      area which determines the depth and width of the necrosis in burns. Many agents
      were proposed to salvage the zone of stasis. Due to the known preventive and
      therapeutic effects of N-acetylcysteine on hepatotoxicity, nephrotoxicity,
      pulmonary injury, and multiple organ failure in humans, the effect of N
      acetylcysteine on saving the zone of stasis was investigated in this experimental
      study. The effects of N-acetylcysteine administration via oral or intraperitoneal
      route was compared in a rat comb-burn model. The extent of burn wounds was
      evaluated by photography and planimetry in the groups. Additionally, skin samples
      were obtained to analyze malondialdehyde levels to see the antioxidant effect of
      N-acetylcysteine. In control group (no treatment), the burn areas went to near
      total necrosis. In intraperitoneal and oral treatment groups, skin survival
      occurred in the interspace area of the comb. There was no difference between the
      groups in terms of MDA concentrations. In conclusion, this study showed us the
      possible saving effect of N-acetylcysteine on the zone of stasis. N
      acetylcysteine may be used in the cases of severe burns, not only for its effects
      on wound healing but also the systemic effects of the drug.

PMID- 22853971
TI  - Psoriasis and metabolic syndrome: is peroxisome proliferator-activated receptor
      gamma part of the missing link?
AB  - BACKGROUND: Growing evidence points to a causative relationship between altered
      activity of peroxisome proliferator-activated receptor gamma (PPARgamma) and
      psoriasis on the one hand, and its relationship with metabolic syndrome (MS) on
      the other. OBJECTIVE: Could altered PPARgamma levels be one of the culprits
      responsible for translating the metabolic state among psoriatic patients?
      MATERIALS AND METHODS: This investigational cross-sectional study included 60
      psoriatics and 60 controls. Subjects were subgrouped according to the presence or
      absence of MS. Biopsies were taken from all subjects for immunohistochemical
      staining for PPARgamma and western blot technique was carried out. RESULTS:
      PPARgamma immunostaining in psoriatics was significantly lower than in controls
      with the lowest levels documented in patients with MS (P<0.001). PPARgamma
      immunostaining level was significantly lower in diabetics, hypertensive and
      insulin resistance patients (P<0.05). It also showed a significant positive
      correlation with high density lipoprotein (HDL) levels and significant negative
      correlation with age, psoriasis area and severity index (PASI), body mass index,
      and blood glucose levels. Similar results were obtained by western blot
      technique. CONCLUSION: Reduced PPARgamma could be added to the factors
      responsible for translating the metabolic state among psoriatic patients.
      PPARgamma agonists can present an adjuvant therapeutic tool in treatment of
      psoriatics with MS.

PMID- 22853973
TI  - Patterns of peripapillary retinal nerve fiber layer thinning in vigabatrin
      exposed individuals.
AB  - PURPOSE: To explore the relationship of peripapillary retinal nerve fiber layer
      (ppRNFL) thinning in individuals exposed to the antiepileptic drug vigabatrin
      with respect to 2 separate variables: cumulative vigabatrin exposure and severity
      of vigabatrin-associated visual field loss (VAVFL). DESIGN: Cross-sectional
      observational study. PARTICIPANTS: Subjects were older than 18 years, 129 with
      vigabatrin-treated epilepsy (vigabatrin-exposed group) and 87 individuals with
      epilepsy never treated with vigabatrin (nonexposed group). METHODS: All subjects
      underwent ppRNFL imaging using spectral-domain optical coherence tomography.
      Eighty-four vigabatrin-exposed individuals underwent Goldmann kinetic perimetry.
      The visual field examined from the right eye was categorized as normal (n = 47),
      mildly abnormal (n = 18), or moderately to severely abnormal (n = 19). In 91
      vigabatrin-exposed individuals, the cumulative vigabatrin exposure could be
      ascertained: 41 subjects received 1000 g or less, 23 subjects received more than
      1000 g but equal to or less than 2500 g, 16 subjects received more than 2500 g
      but equal to or less than 5000 g or less, and 11 subjects received more than 5000
      g. MAIN OUTCOME MEASURES: Differences in ppRNFL thickness across the twelve 30
      degrees  sectors: (1) among all nonexposed individuals and all vigabatrin-exposed
      individuals, (2) between each vigabatrin-exposed group, according to cumulative
      vigabatrin exposure, and the nonexposed group, (3) among different vigabatrin
      exposed subjects grouped according to cumulative vigabatrin exposure, and (4)
      among vigabatrin-exposed subjects grouped according to severity of VAVFL.
      RESULTS: The ppRNFL was significantly thinner in vigabatrin-exposed compared with
      nonexposed individuals in most 30 degrees  sectors (P<0.004). The temporal,
      temporal superior, and temporal inferior 30 degrees  sectors, as well as the
      nasal 30 degrees  sector, were not affected. There was a trend for increasing
      ppRNFL thinning with increasing cumulative vigabatrin exposure. The nasal
      superior 30 degrees  sector was significantly thinner in group 1 (<=1000 g)
      compared with nonexposed individuals (P<0.05) and in vigabatrin-exposed
      individuals with normal visual fields compared with nonexposed individuals
      (P<0.05). CONCLUSIONS: After vigabatrin exposure in individuals receiving
      cumulative doses of 1000 g or less or in the presence of normal visual fields,
      ppRNFL thinning in the nasal superior 30 degrees  sector may occur. With higher
      cumulative doses of vigabatrin exposure, additional ppRNFL thinning was observed.
      The temporal aspects of the ppRNFL are spared, even in individuals with large
      cumulative vigabatrin exposures and moderate or severe VAVFL.

PMID- 22853972
TI  - Risk of cataract in persons with cytomegalovirus retinitis and the acquired
      immune deficiency syndrome.
AB  - OBJECTIVE: To evaluate cataract risk in eyes of patients with AIDS and
      cytomegalovirus (CMV) retinitis and to identify risk factors. DESIGN: Prospective
      cohort study. PARTICIPANTS: Patients with AIDS and CMV retinitis. METHODS:
      Patients 13 years of age and older were enrolled between 1998 and 2008.
      Demographic and clinical characteristics, slit-lamp biomicroscopy findings, and
      dilated ophthalmoscopy results were documented at quarterly visits. Cataract
      status was determined at the initial visit (prevalence) and at follow-up visits
      (incidence). MAIN OUTCOME MEASURES: For cataract, a high grade of lens opacity by
      biomicroscopy to which best-corrected visual acuity worse than 20/40 was
      attributed. Eyes that had undergone cataract surgery before enrollment or between
      visits also were counted as having cataract. RESULTS: Seven hundred twenty-nine
      eyes of 489 patients diagnosed with CMV retinitis were evaluated. Higher
      prevalence was observed for patients with bilateral versus unilateral CMV
      retinitis (adjusted odds ratio [aOR], 2.74; 95% confidence interval [CI], 1.76
      4.26) and, among unilateral CMV retinitis cases, for eyes with retinitis versus
      without retinitis (15% vs. 1.4%; P<0.0001). The age-adjusted prevalence of
      cataract among CMV retinitis cases was higher than that in a population-based
      sample (P<0.0001). Cataract prevalence increased with age (aOR, 11.77; 95% CI,
      2.28-60.65 for age >= 60 years vs. younger than 40 years) and longer duration of
      retinitis (aOR, 1.36; 95% CI, 1.20-1.54 per year). Among eyes with CMV retinitis
      initially free of cataract, the cataract incidence was 8.1%/eye-year (95% CI,
      6.7%-10.0%). Prior retinal detachment was associated with higher cataract risk
      (if repaired with silicone oil: adjusted hazard ratio [aHR], 10.37; 95% CI, 6.51
      16.52; otherwise: aHR, 2.90; 95% CI, 1.73-4.87). Large CMV retinitis lesions also
      were associated with higher risk of cataract (for involvement of 25-49% retinal
      area: aHR, 2.30; 95% CI, 1.51-3.50; for >= 50% involvement: aHR, 3.63; 95% CI,
      2.18-6.04), each with respect to <= 24% involvement, as were anterior segment
      inflammation (aHR, 2.27; 95% CI, 1.59-3.25) and contralateral cataract (aHR,
      2.52; 95% CI, 1.74-3.66). CONCLUSIONS: Cytomegalovirus retinitis is associated
      with a high absolute and relative risk of cataract. Among several risk factors,
      large retinal lesion size and use of silicone oil in retinal detachment repair
      are potentially modifiable, albeit not in all cases. Cataract is likely to be an
      increasingly important cause of visual morbidity in this population.

PMID- 22853974
TI  - Evaluation of DNA extraction methods for freshwater eukaryotic microalgae.
AB  - The use of molecular methods to investigate microalgal communities of natural and
      engineered freshwater resources is in its infancy, with the majority of previous
      studies carried out by microscopy. Inefficient or differential DNA extraction of
      microalgal community members can lead to bias in downstream community analysis.
      Three commercially available DNA extraction kits have been tested on a range of
      pure culture freshwater algal species with diverse cell walls and mixed algal
      cultures taken from eutrophic waste stabilization ponds (WSP). DNA yield and
      quality were evaluated, along with DNA suitability for amplification of 18S rRNA
      gene fragments by polymerase chain reaction (PCR). QiagenDNeasy((r)) Blood and
      Tissue kit (QBT), was found to give the highest DNA yields and quality.
      Denaturant Gradient Gel Electrophoresis (DGGE) was used to assess the diversity
      of communities from which DNA was extracted. No significant differences were
      found among kits when assessing diversity. QBT is recommended for use with WSP
      samples, a conclusion confirmed by further testing on communities from two
      tropical WSP systems. The fixation of microalgal samples with ethanol prior to
      DNA extraction was found to reduce yields as well as diversity and is not
      recommended.

PMID- 22853975
TI  - Characterization of low molecular weight dissolved natural organic matter along
      the treatment trait of a waterworks using Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - Dissolved natural organic matter (DOM), particularly the low molecular weight
      DOM, can affect the performance of water treatment processes and serve as a main
      precursor of disinfection by-products (DBPs) during chlorination. In this study,
      electrospray ionization coupled to Fourier transform ion cyclotron resonance mass
      spectrometry (ESI FT-ICR MS) was used to characterize the low molecular weight
      DOM along the treatment trait of a conventional drinking water treatment plant.
      The ESI FT-ICR MS data showed that various C, H, O-only class species were the
      major components in the source water. According to the van Krevelen diagram
      analysis, lignin- and tannin-like compounds were the most abundant components.
      Within an isobaric group, the DOM molecules with a high degree of oxidation (high
      O/C value) were preferentially removed during coagulation, while those with low
      degree of oxidation were found to be more reactive toward chlorine. In addition,
      357 one-chlorine containing products and 199 two-chlorine containing products
      formed during chlorination were detected in the chlorination effluent sample at a
      high confidence level. The chlorinated products can be arranged into series,
      suggesting that they were originated from C, H, O-only precursor compounds, which
      were in series related by the replacement of CH(4) against oxygen. For the first
      time, this study explored the behavior of low molecular weight DOM along a
      drinking water treatment trait on the molecular level, and revealed the presence
      of abundant unknown chlorinated products, which are probably rich in carboxylic
      and phenolic groups, in drinking water.

PMID- 22853976
TI  - Statistical tracking of tree-like tubular structures with efficient branching
      detection in 3D medical image data.
AB  - The segmentation of tree-like tubular structures such as coronary arteries and
      airways is an essential step for many 3D medical imaging applications.
      Statistical tracking techniques for the extraction of elongated structures have
      received considerable attention in recent years due to their robustness against
      image noise and pathological changes. However, most tracking methods are limited
      to a specific application and do not support branching structures efficiently. In
      this work, we present a novel statistical tracking approach for the extraction of
      different types of tubular structures with ringlike cross-sections. Domain
      specific knowledge is learned from training data sets and integrated into the
      tracking process by simple adaption of parameters. In addition, an efficient
      branching detection algorithm is presented. This approach was evaluated by
      extracting coronary arteries from 32 CTA data sets and distal airways from 20 CT
      scans. These data sets were provided by the organizers of the workshop '3D
      Segmentation in the Clinic: A Grand Challenge II-Coronary Artery Tracking
      (CAT08)' and 'Extraction of Airways from CT 2009 (EXACT'09)'. On average, 81.5%
      overlap and 0.51 mm accuracy for the tracking of coronary arteries were achieved.
      For the extraction of airway trees, 51.3% of the total tree length, 53.6% of the
      total number of branches and a 4.98% false positive rate were attained. In both
      experiments, our approach is comparable to state-of-the-art methods.

PMID- 22853977
TI  - Changes in overnight arterial oxygen saturation after mandibular setback.
AB  - Mandibular setback reduces space in the pharyngeal airway, and it has been
      suggested that it might induce sleep-disordered breathing. We report on its
      effects on space in the pharyngeal airway and respiratory function during sleep.
      We studied 78 patients (29 men and 49 women) in whom skeletal class III
      malocclusions had been corrected. The mean (range) age at operation was 24 (16
      38) years and body mass index (BMI) 21.4 (16.1-30 .9)kg/m(2). Morphological
      changes were evaluated on lateral cephalograms taken three times: preoperatively,
      a few days postoperatively, and more than 6 months postoperatively. Overnight
      arterial oxygen saturation (SpO2) was measured by pulse oximetry 6 times:
      preoperatively, and on days 1, 3, 5, and 7, and 6 months postoperatively;
      oximetric indices were calculated. Those immediately after mandibular setback
      were significantly worse than those preoperatively, although they gradually
      improved. There were positive correlations between BMI and oximetric indices, and
      little association between changes in mandibular position and oximetric indices.
      There was no evidence of sleep-disordered breathing 6 months after mandibular
      setback because most patients adapt to the new environment for respiratory
      function during sleep. However, some (particularly obese) patients may develop
      sleep-disordered breathing just after mandibular setback. In such patients
      attention should be paid to respiratory function during sleep in the immediate
      postoperative period, and careful postoperative follow-up is needed.

PMID- 22853978
TI  - The use of sports psychology models to combat anxiety and improve performance
      within oral and maxillofacial surgery.

PMID- 22853979
TI  - Intraoperative lacrimal intubation to prevent epiphora as a result of injury to
      the nasolacrimal system after fracture of the naso-orbitoethmoid complex.
AB  - Treatment of fracture of the naso-orbitoethmoid (NOE) complex is difficult. There
      are not only aesthetic issues but also functional consequences related to the
      lacrimal system. Because prophylactic lacrimal intubation for such fractures
      remains controversial, we have assessed the effectiveness of intraoperative
      lacrimal intubation to prevent epiphora as a result of such injuries. Thirteen
      patients diagnosed with craniomaxillofacial fractures including fractures of the
      NOE complex were included in the study; 10 had unilateral fractures and 3
      bilateral. Computed tomography (CT) showed all patients had displaced fragments
      that had the potential to damage the lacrimal duct. In 7 patients the fractures
      included the canthal region and in 6 they did not. All patients were treated by
      open reduction and internal fixation under general anaesthesia, followed by
      intraoperative lacrimal intubation unilaterally or bilaterally as required.
      Lacrimal intubation with a silicone tube was successful in all 13 patients (16
      sides). The tube was removed 2-9 months (mean 3.8) postoperatively and no
      subsequent epiphora were seen during follow-up (mean (3-29 months) 11.3 months).
      Lacrimal intubation for at least 2 months may prevent epiphora caused by injury
      to the nasolacrimal system after fractures of the NOE complex.

PMID- 22853980
TI  - A randomized, double-blind, phase III study of Docetaxel and Ramucirumab versus
      Docetaxel and placebo in the treatment of stage IV non-small-cell lung cancer
      after disease progression after 1 previous platinum-based therapy (REVEL):
      treatment rationale and study design.
AB  - This article describes the treatment rationale and study-related procedures for
      the A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus
      Docetaxel and Placebo in the Treatment of Stage IV Non-Small-Cell Lung Cancer
      Following Disease Progression after One Prior Platinum-Based Therapy (REVEL)
      study (I4T-MC-JVBA; ClinicalTrials.govNCT01168973). This international,
      randomized, placebo-controlled, double-blinded phase III trial examines the
      efficacy and safety of ramucirumab treatment administered in combination with
      docetaxel, as compared with docetaxel administered with placebo, in patients with
      stage IV non-small-cell lung cancer (NSCLC) whose disease progressed during or
      after first-line platinum-based chemotherapy with or without maintenance
      treatment. The primary end point is overall survival; secondary end points
      include progression-free survival, objective response rate, disease control rate,
      patient-reported outcomes, and assessment of safety and tolerability of
      ramucirumab. Eligible patients (enrollment N = 1242) are randomized at a 1:1
      ratio to receive either docetaxel (75 mg/m(2)) plus ramucirumab (10 mg/kg) (Arm
      A) or docetaxel (75 mg/m(2)) plus placebo (Arm B). Both drugs are administered
      via intravenous infusion once every 3 weeks until evidence of disease
      progression, unacceptable toxicity, noncompliance, or patient's consent
      withdrawal. Efficacy and safety will be compared between the study arms and in
      patient subgroups including patients with nonsquamous versus squamous tumor
      histology and patients who received prior bevacizumab treatment. Multiple blood
      and tumor tissue biomarker samples are collected during the study. The goal of
      the REVEL study is to demonstrate that ramucirumab in combination with docetaxel
      improves overall survival of patients with NSCLC with progressive disease after
      first-line therapy, and to advance our knowledge of the role of angiogenesis
      blockade in patients with NSCLC by identifying patients who are likely to
      experience maximum benefit based on extensive clinical biomarker correlative
      analysis.

PMID- 22853981
TI  - State of the art radiation therapy for lung cancer 2012: a glimpse of the future.
AB  - The prognosis of patients with lung cancer has improved over the past years.
      Patient selection, optimal sequencing of systemic and local treatments, and
      better surgical techniques, together with unprecedented improvements in imaging
      and computer technology and technical advances in radiation therapy planning and
      delivery has revolutionized radiation therapy in a short period of time. Among
      the most significant evolutions that have direct implications for daily practice
      are the more widespread use of stereotactic body radiation for stage I non-small
      cell lung cancer (NSCLC), concurrent chemoradiation for stage III NSCLC, the
      implementation of 4-dimensional computed tomography and positron emission
      tomography, adaptive radiation therapy strategies, optimizing the timing of chest
      radiation therapy for limited disease small-cell lung cancer (SCLC) and
      prophylactic cranial irradiation for extensive disease SCLC. Molecular-based
      individualized radiation therapy dose prescription, which goes hand in hand with
      the realization of decision-support systems and the introduction of proton
      therapy centers give only a glimpse of what the future will bring.

PMID- 22853983
TI  - Comparative one-year effectiveness of percutaneous coronary intervention versus
      coronary artery bypass grafting in patients <75 versus >=75 years with
      unprotected left main disease (from the CUSTOMIZE Registry).
AB  - There is a lack of knowledge on the interaction between age and left main
      coronary artery revascularization. The aim of this study was to investigate the
      comparative effectiveness of percutaneous coronary intervention (PCI) with drug
      eluting stents and coronary artery bypass grafting (CABG) in patients with left
      main coronary artery disease aged <75 versus >=75 years. Of a total of 894
      patients included, 692 (77.4%) were aged <75 years and 202 (23.6%) >=75 years.
      PCI was found to be significantly different from CABG with respect to the
      composite of major adverse cardiac events at 1-year follow-up in patients aged
      <75 years (15.5% vs 8.5%, p = 0.01) but not in those aged >=75 years (16.4% vs
      13.9%, p = 0.65). This finding was consistent after statistical adjustment for
      baseline confounders in the 2 groups (adjusted hazard ratio [AHR] 2.2, 95%
      confidence interval 1.2 to 4.1, p = 0.016 in younger patients; AHR 0.9, 95%
      confidence interval 0.3 to 3.0, p = 0.88 in older patients). In the 2 groups, PCI
      and CABG showed similar adjusted risks for all-cause death, cardiac death, and
      myocardial infarction. Target lesion revascularization occurred more frequently
      in patients aged <75 years treated with PCI compared to CABG (AHR 5.1, 95%
      confidence interval 1.9 to 13.6, p = 0.001) but not in those aged >=75 years. A
      significant interaction between age and treatment with regard to major adverse
      cardiac events was identified (adjusted p for interaction = 0.034). In
      conclusion, compared to younger patients, elderly patients with left main disease
      are likely to derive the maximal gain from a less invasive procedure such as PCI.

PMID- 22853982
TI  - Incidence and predictors of 30-day hospital readmission rate following
      percutaneous coronary intervention (from the National Heart, Lung, and Blood
      Institute Dynamic Registry).
AB  - Postdischarge outcomes after percutaneous coronary intervention (PCI) are
      important measurements of quality of care and complement in-hospital
      measurements. We sought to assess in-hospital and postdischarge PCI outcomes to
      (1) better understand the relation between acute and 30-day outcomes, (2)
      identify predictors of 30-day hospital readmission, and (3) determine the
      prognostic significance of 30-day hospital readmission. We analyzed in-hospital
      death and length of stay (LOS) and nonelective cardiac-related rehospitalization
      after discharge in 10,965 patients after PCI in the Dynamic Registry. From 1999
      to 2006 in-hospital death rate and LOS decreased. Thirty-day cardiac readmission
      rate was 4.6%, with considerable variability over time and among hospitals. Risk
      of rehospitalization was greater in women and those with congestive heart
      failure, unstable angina, multiple lesions, and emergency PCI. Conversely, a
      lower risk of rehospitalization was associated with a larger number of treated
      lesions. Patients readmitted within 30 days had higher 1-year mortality than
      those free from hospital readmission. In conclusion, although in-hospital
      mortality and LOS after PCI have decreased over time, the observed 30-day cardiac
      readmission rate was highly variable and risk of readmission was more closely
      associated with underlying patient characteristics than procedural
      characteristics.

PMID- 22853984
TI  - Effect of early bereavement on heart rate and heart rate variability.
AB  - Early bereavement is associated with increased cardiovascular events. The
      mechanism, however, has not been well studied. We assessed whether bereavement is
      associated with an increased heart rate (HR) and decreased heart rate variability
      that might contribute to increased cardiovascular risk. A total of 78 bereaved
      spouses and parents (55 women and 23 men; aged 34 to 87 years, mean 65) were
      studied with 24-hour Holter monitoring within 2 weeks of bereavement (acute) and
      at 6 months. Their findings were compared to those from a nonbereaved reference
      group (52 women and 27 men) aged 33 to 91 years (mean 63.6). All participants
      were in sinus rhythm. We assessed the mean HR, atrial and ventricular
      arrhythmias, and both time and frequency domain heart rate variability measures.
      Acute bereavement was associated with increased 24-hour HR (mean +/- SE, 75.1 +/-
      1.1 vs 70.7 +/- 1.0; p = 0.004) and reduced heart rate variability, as indicated
      by lower standard deviation of the NN intervals index (median 45.4 vs 49.9, p =
      0.017), total power (7.78 +/- 0.10 vs 8.02 +/- 0.09, p = 0.03), very low
      frequency (7.23 +/- 0.09 vs 7.44, p = 0.046) and low frequency (5.76 +/- 0.12 vs
      6.16 +/- 0.09, p = 0.01). At 6 months, the bereaved had a significantly lower HR
      (p = 0.001) and increased standard deviation of the NN intervals index (p =
      0.02), square root of the mean square of differences of successive intervals (p =
      0.045), number of interval differences of successive NN intervals >50 ms divided
      by the number of NN intervals (p = 0.039), low-frequency power (p = 0.02), and
      high frequency (p = 0.002) compared to the initial acute levels. In conclusion,
      the present study, the first to report 24-hour HR monitoring in the early weeks
      of bereavement, has demonstrated increased HR and altered autonomic function that
      might contribute to the increased cardiovascular events in early bereavement.

PMID- 22853985
TI  - Percutaneous balloon-expandable covered stent implantation for treatment of
      traumatic aortic injury in children and adolescents.
AB  - Surgical treatment of pediatric acute traumatic aortic injury (TAI) after blunt
      chest trauma is standard of care. Use of endovascular stent grafts for treatment
      of TAI in adults is common but has important limitations in children. We sought
      to describe the use of balloon-expandable covered endovascular stents for
      treatment of TAI in children and adolescents. Participants of the multicenter
      Coarctation of the Aorta Stent Trial (COAST) had access to investigational large
      diameter, balloon-expandable, covered stents (covered Cheatham-platinum stents;
      NuMed, Inc., Hopkinton, New York) on an emergency-use basis. From 2008 through
      2011, 6 covered stents were implanted in 4 patients at 3 COAST centers for
      treatment of TAI. Median patient age was 13.5 years (range 11 to 14) and weight
      was 58 kg (40 to 130). All patients sustained severe extracardiac injuries that
      were judged to preclude safe open surgical repair of TAI. Median aortic isthmus
      and stent implantation balloon diameters were 16.4 mm (13.2 to 19) and 19 mm (16
      to 20), respectively. Stent implantation was technically successful in all
      attempts. Complete exclusion of aortic wall injury was achieved in all cases.
      There were no access site complications. At a median follow-up of 24 months,
      there was 1 early death (related to underlying head trauma) and 1 patient with
      recurrent aortic aneurysm who required additional stent implantation. In
      conclusion, balloon-expandable covered-stent implantation for treatment of
      pediatric TAI after blunt trauma is generally safe and effective. Availability of
      this equipment may alter the standard approach to treatment of pediatric TAI.

PMID- 22853986
TI  - Safety and efficacy of transition from systemic prostanoids to inhaled
      treprostinil in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a disease characterized by increased
      pulmonary pressures and chronic right heart failure. Therapies for moderate and
      severe PAH include subcutaneous (SQ) and intravenous (IV) prostanoids that
      improve symptoms and quality of life. However, treatment compliance can be
      limited by severe side effects and complications related to methods of drug
      administration. Inhaled prostanoids, which offer the advantage of direct delivery
      of the drug to the pulmonary circulation without need for invasive approaches,
      may serve as an alternative for patients unable to tolerate SQ/IV therapy. In
      this retrospective cohort study we collected clinical, hemodynamic, and
      functional data from 18 clinically stable patients with World Health Organization
      group I PAH seen in 6 large national PAH centers before and after transitioning
      to inhaled treprostinil from IV/SQ prostanoids. Before transition 15 patients had
      been receiving IV or SQ treprostinil (mean dose 73 ng/kg/min) and 3 patients had
      been on IV epoprostenol (mean dose 10 ng/kg/min) for an average duration of 113
      +/- 80 months. Although most patients who transitioned to inhaled treprostinil
      demonstrated no statistically significant worsening of hemodynamics or 6-minute
      walk distance, a minority demonstrated worsening of New York Heart Association
      functional class over a 7-month period. In conclusion, although transition of
      patients from IV/SQ prostanoids to inhaled treprostinil appears to be well
      tolerated in clinically stable patients, they should remain closely monitored for
      signs of clinical decompensation.

PMID- 22853987
TI  - Updated US Department of Agriculture Food Patterns meet goals of the 2010 dietary
      guidelines.
AB  - The US Department of Agriculture Food Patterns were updated for the 2010 Dietary
      Guidelines for Americans to meet new nutrition goals and incorporate results of
      food pattern modeling requested by the Dietary Guidelines Advisory Committee. The
      purpose of this article is to describe the process used and changes in the
      updated patterns. Changes include renaming the Meat and Beans and Milk Groups to
      the Protein Foods and Dairy Groups, respectively, to be more encompassing of
      foods in each. Vegetable subgroups now provide more achievable intake
      recommendations. Calcium-fortified soymilk is now included in the Dairy Group
      because of its similarity to foods in that group. Increased amounts of seafoods
      are recommended in the Protein Foods Group, balanced by decreased amounts of meat
      and poultry. A limit on calories from solid fats and added sugars is included,
      replacing the previous discretionary calorie allowance and emphasizing the need
      to choose nutrient-dense forms of foods. Lacto-ovo vegetarian and vegan patterns
      that meet nutrition goals were created by making substitutions in the Protein
      Foods Group, and for vegan patterns, in the Dairy Group. Patterns identify food
      choices that meet nutritional needs within energy allowances and encourage
      choosing a variety of foods. They rely on foods in nutrient-dense forms,
      including a limited amount of calories from solid fats and added sugars. The Food
      Patterns provide a useful template for educating consumers about healthful food
      choices while highlighting a large gap between choices many Americans make and
      healthy eating patterns.

PMID- 22853989
TI  - Linking coral river runoff proxies with climate variability, hydrology and land
      use in Madagascar catchments.
AB  - Understanding the linkages between coastal watersheds and adjacent coral reefs is
      expected to lead to better coral reef conservation strategies. Our study aims to
      examine the main predictors of environmental proxies recorded in near shore
      corals and therefore how linked near shore reefs are to the catchment physical
      processes. To achieve these, we developed models to simulate hydrology of two
      watersheds in Madagascar. We examined relationships between environmental proxies
      derived from massive Porites spp. coral cores (spectral luminescence and
      barium/calcium ratios), and corresponding time-series (1950-2006) data of
      hydrology, climate, land use and human population growth. Results suggest
      regional differences in the main environmental drivers of reef sedimentation: on
      annual time-scales, precipitation, river flow and sediment load explained the
      variability in coral proxies of river discharge for the northeast region, while
      El Nino-Southern Oscillation (ENSO) and temperature (air and sea surface) were
      the best predictors in the southwest region.

PMID- 22853988
TI  - A novel measure of dietary change in a prostate cancer dietary program
      incorporating mindfulness training.
AB  - Diet may represent a modifiable prostate cancer risk factor, but a vegetable
      based prostate-healthy diet is a major change for most men. We used a ratio of
      animal to vegetable proteins (A:V) to evaluate whether a comprehensive dietary
      change was self-sustaining following completion of 11 weekly dietary and cooking
      classes that integrated mindfulness training. Thirty-six men with recurring
      prostate cancer were randomized to the intervention or wait-list control.
      Assessments were at baseline, 3 months, and 6 months. Of 17 men randomized to the
      intervention, 14 completed the requirements. Nineteen were randomized to control
      and 17 completed requirements. Compared with controls, a significant
      postintervention (3 months) decrease in A:V in the intervention group (P=0.01)
      was self-maintained 3 months postintervention (P=0.049). At each assessment, A:V
      was correlated with lycopene, fiber, saturated fat, and dietary cholesterol, four
      dietary components linked to clinically relevant outcomes in prostate cancer.
      Change in A:V was also significantly correlated with changes in fiber, saturated
      fat, and dietary cholesterol intake. Participants reported regular mindfulness
      training practice, and there was a significant correlation between mindfulness
      training practice and changes in both initiation and maintenance of the change in
      A:V. These pilot results provide encouraging evidence for the feasibility of a
      dietary program that includes mindfulness training in supporting dietary change
      for men with recurrent prostate cancer and invite further study to explore the
      possible role of mindfulness training as a means of supporting both initiation of
      dietary changes and maintenance of those changes over time.

PMID- 22853990
TI  - Comparative efficiency of macroalgal extracts and booster biocides as antifouling
      agents to control growth of three diatom species.
AB  - The application of 'booster biocides' Diuron, Tolylfluanid and Copper thiocyanate
      inbantifouling paints, used to prevent development of biofouling, needs to be
      monitored before assessing their impacts on the environment. An alternative
      approach aims to propose eco-friendly and effective antifoulants isolated from
      marine organisms such as seaweeds. In this study, the effects of 'booster
      biocides' and the ethanol and dichloromethane extracts from a brown (Sargassum
      muticum) and a red alga (Ceramium botryocarpum) have been compared by algal
      growth inhibition tests of marine diatoms. The most efficient extracts were
      ethanol fraction of S. muticum and C. botryocarpum extracts with growth
      EC(50)=4.74 and 5.3MUg mL(-1) respectively, with reversible diatom growth effect.
      The booster biocides are more efficient EC(50)=0.52MUg mL(-1), but are highly
      toxic. Results validate the use of macroalgal extracts as non toxic antifouling
      compounds, and they represent valuable environmentally friendly alternatives in
      comparison with currently used biocides.

PMID- 22853992
TI  - Synthesis and characterization of alphavbeta3-targeting peptidomimetic chelate
      conjugates for PET and SPECT imaging.
AB  - There is growing interest in small peptidomimetic alpha(v)beta(3) integrin
      antagonists that are readily synthesized and characterized and can be easily
      handled using physiological conditions. Peptidomimetic 4-[2-(3,4,5,6
      tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1
      carbamyl)]-aminoethylsulfonyl-amino-beta-alanine (IAC) was successfully
      conjugated to 1-(1-carboxy-3-carbo-t-butoxypropyl)-4,7-(carbo-tert-butoxymethyl)
      1,4,7-triazacyclononane (NODA-GA(tBu)(3)) and 1-(1-carboxy-3
      carbotertbutoxymethyl)-1,4,7,10-tetraazacyclododecane (DOTA-GA(tBu)(4)) and
      radiolabeled with (111)In, (67)Ga and (203)Pb. Results of a radioimmunoassay
      demonstrated binding to purified alpha(v)beta(3) integrin when 1-4equiv of
      integrin were added to the reaction. Based on this promising result,
      investigations are moving forward to evaluate the NODA-GA-IAC and DOTA-GA-IAC
      conjugates for targeting tumor associated angiogenesis and alpha(v)beta(3)
      integrin positive tumors to define their PET and SPECT imaging qualities as well
      as their potential for delivery of therapeutic radionuclides.

PMID- 22853993
TI  - A combined targeted/phenotypic approach for the identification of new
      antiangiogenics agents active on a zebrafish model: from in silico screening to
      cyclodextrin formulation.
AB  - A combined targeted/phenotypic approach for the rapid identification of novel
      antiangiogenics with in vivo efficacy is herein reported. Considering the
      important role played by the tyrosine kinase c-Src in the regulation of tumour
      angiogenesis, we submitted our in-house library of c-Src inhibitors to a
      sequential screening approach: in silico screening on VEGFR2, in vitro screening
      on HUVEC cells, ADME profiling, formulation and in vivo testing on a zebrafish
      model. A promising antiangiogenic candidate able to interfere with the vascular
      growth of a zebrafish model at low micromolar concentration was thus identified.

PMID- 22853994
TI  - Fluorogenic assay of alkaline phosphatase activity based on the modulation of
      excited-state intramolecular proton transfer.
AB  - A new fluorogenic substrate 1, which enables the fast and quantitative analysis
      of alkaline phosphatase activity, has been developed. Selective enzymatic
      hydrolysis of 1 instantly generated fluorescent compound 2 in aqueous media,
      which undergo an excited-state intramolecular proton transfer process, resulting
      in a remarkable fluorescence turn-on signal with an unusually large Stokes shift.

PMID- 22853995
TI  - 4-Substituted boro-proline dipeptides: synthesis, characterization, and
      dipeptidyl peptidase IV, 8, and 9 activities.
AB  - The boroProline-based dipeptidyl boronic acids were among the first DPP-IV
      inhibitors identified, and remain the most potent known. We introduced various
      substitutions at the 4-position of the boroProline ring regioselectively and
      stereoselectively, and incorporated these aminoboronic acids into a series of 4
      substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg
      (4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while
      (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8
      and DPP9.

PMID- 22853996
TI  - Two novel bioactive glucosinolates from Broccoli (Brassica oleracea L. var.
      italica) florets.
AB  - Two novel glucosinolates along with one known glucosinolate were isolated from
      Broccoli (Brassica oleracea L. var. italica) florets. Their structures were
      established mainly by 1D ((1)H and (13)C NMR), 2D NMR ((1)H-(1)H COSY, DEPT 135
      degrees , HSQC and HMBC), and Tandem MS-MS spectrometric data as 2-mercaptomethyl
      sulfinyl glucosinolate [(Z)-4-(methylsulfinyl)-N-(sulfooxy)-2
      ((2'S,3'R,4'S,5'S,6'R)-3',4',5'-trihydroxy-6'(hydroxylmethyl)-2'-mercapto
      tetrahydro-2H-pyran-2-yl) butane amide] 1, (Z)-1-((2S,5S)-5-hydroxytetra-hydro-2H
      pyran-2-ylthio)-2-(1H-indol-3-yl) ethylidene amino sulfate 2 and a known
      cinnamoyl [6'-O-trans-(4"-hydroxy cinnamoyl)4-(methylsulphinyl)butyl
      glucosinolate] 3. Compound 1 exhibited scavenging activity against DPPH with an
      inhibitory concentration IC(50) of 20 mM, whereas compound 3 was a weak
      antioxidant when compared to the standard quercetin (5 mM) as a positive control.
      Both the compounds showed a significant and similar antimicrobial activity
      against Staphylococcus aureus with an IC(50) of <625 MUg/mL when compared to
      antibiotic duricef. Against Salmonella typhimurium the IC(50) of 1 and 3 was
      determined as <625 MUg/mL and <1250 MUg/mL, respectively, when compared to
      ampicillin (IC(50) <= 39 MUg/mL) as a positive control.

PMID- 22853997
TI  - Orally available pyridinylpyrimidine derivatives as novel RANKL-induced
      osteoclastogenesis inhibitors.
AB  - An HTS campaign led to the identification of 4-pyrroldino-2-(pyridin-2
      yl)pyrimidine compound 1 as an RANKL-induced osteoclastogenesis inhibitor. The
      compound 1 showed high clearance values in microsomes, however. Modification of
      the pyrrolidino group to a benzylamino group improved human microsomal stability
      with a slight loss of in vitro activity. Substitution at the ortho position of
      the benzyl group ameliorated in vitro activity, and further fluorination of the
      benzyl group improved microsomal stability in rodents. Representative members of
      this series, compounds 20 and 23, exhibited efficacy in RANKL-induced osteopenic
      mice when administered orally at 0.3 mg/kg.

PMID- 22853998
TI  - Design, synthesis and identification of novel benzimidazole derivatives as highly
      potent NPY Y5 receptor antagonists with attractive in vitro ADME profiles.
AB  - Optimization of our HTS hit 1, mainly focused on modification at the C-2 position
      of the benzimidazole core, is described. Elimination of the flexible and
      metabolically labile -S-CH(2)- part and utilization of less lipophilic pyridone
      substructure led to identification of novel NPY Y5 receptor antagonists 6, which
      have low to sub-nanomolar Y5 receptor binding affinity with improved CYP450
      inhibition profiles, good solubilities and high metabolic stabilities.

PMID- 22853999
TI  - Analysis of convergence performance of neural networks ranking algorithm.
AB  - The ranking problem is to learn a real-valued function which gives rise to a
      ranking over an instance space, which has gained much attention in machine
      learning in recent years. This article gives analysis of the convergence
      performance of neural networks ranking algorithm by means of the given samples
      and approximation property of neural networks. The upper bounds of convergence
      rate provided by our results can be considerably tight and independent of the
      dimension of input space when the target function satisfies some smooth
      condition. The obtained results imply that neural networks are able to adapt to
      ranking function in the instance space. Hence the obtained results are able to
      circumvent the curse of dimensionality on some smooth condition.

PMID- 22854000
TI  - Non-pigmenting fixed drug eruption caused by an over-the-counter non-steroidal
      anti-inflammatory drug: drug-specific CD8+ T lymphocytes identified in peripheral
      blood.

PMID- 22854001
TI  - The Utstein-style Template for uniform data reporting of acute medical response
      in disasters.

PMID- 22854002
TI  - Basic-level emergency medical technician administration of fluids and glucose via
      enzyme-assisted subcutaneous infusion access.
AB  - INTRODUCTION: During disasters and mass-casualty incidents (MCIs), there may be
      insufficient numbers of advanced life support (ALS) providers to provide
      intravenous (IV) access to all patients requiring parenteral fluids and/or
      medications. Enzyme-assisted subcutaneous infusion (EASI) access, in which human
      recombinant hyaluronidase (HRH) augments subcutaneous fluid dispersion and
      absorption, may be useful when ALS resources are insufficient to meet
      intravascular access needs. The utility of the use of the EASI lies, in part, in
      its ease of placement by ALS personnel. OBJECTIVES: The objectives of this study
      were to document the feasibility, comfort, and speed/degree of infused-glucose
      uptake through EASI lines placed by basic-level emergency medical technicians
      (EMT-Bs). METHODS: Eighteen EMT-Bs instituted EASI access on each other. A total
      of 150 units (1 mL) of HRH were administered through the EASI line, followed by
      the administration of 250 mL of tracer-labeled D5W. Timed phlebotomy enabled gas
      chromatography/mass spectrometry characterization of glucose uptake. Enzyme
      assisted subcutaneous infusion placement and comfort ratings were tracked and
      analyzed using non-parametric statistics and Fisher's Exact Test. RESULTS: In all
      18 subjects, EASI access required only one attempt and was rated by the EMT-Bs as
      easy to accomplish. Glucose was absorbed quickly (within five minutes) in all
      subjects. The rate of infusion was rapid (median 393 mL/hour) and was comfortable
      for the recipients (median pain score 1/10). CONCLUSIONS: The use of EASI may be
      viable as a fast, simple, and reliable method for the administration of fluid and
      glucose by EMT-Bs.

PMID- 22854003
TI  - The accuracy of emergency medical dispatcher-assisted layperson-caller pulse
      check using the medical priority dispatch system protocol.
AB  - INTRODUCTION: Knowing the pulse rate of a patient in a medical emergency can help
      to determine patient acuity and the level of medical care required. Little
      evidence exists regarding the ability of a 911 layperson-caller to accurately
      determine a conscious patient's pulse rate. Hypothesis The hypothesis of this
      study was that, when instructed by a trained emergency medical dispatcher (EMD)
      using the scripted Medical Priority Dispatch System (MPDS) protocol Pulse Check
      Diagnostic Tool (PCDxT), a layperson-caller can detect a carotid pulse and
      accurately determine the pulse rate in a conscious person. METHODS: This non
      randomized and non-controlled prospective study was conducted at three different
      public locations in the state of Utah (USA). A healthy, mock patient's pulse rate
      was obtained using an electrocardiogram (ECG) monitor. Layperson-callers, in
      turn, initiated a simulated 911 phone call to an EMD call-taker who provided
      instructions for determining the pulse rate of the patient. Layperson accuracy
      was assessed using correlations between the layperson-caller's finding and the
      ECG reading. RESULTS: Two hundred sixty-eight layperson-callers participated; 248
      (92.5%) found the pulse of the mock patient. There was a high correlation between
      pulse rates obtained using the ECG monitor and those found by the layperson
      callers, overall (94.6%, P < .001), and by site, gender, and age. CONCLUSIONS:
      Layperson-callers, when provided with expert, scripted instructions by a trained
      911 dispatcher over the phone, can accurately determine the pulse rate of a
      conscious and healthy person. Improvements to the 911 instructions may further
      increase layperson accuracy.

PMID- 22854004
TI  - Mechanisms of increased passive compliance of hamstring muscle-tendon units after
      spinal cord injury.
AB  - BACKGROUND: People with spinal cord injury sometimes develop abnormally compliant
      hamstring muscle-tendon units. This study investigated whether the increased
      muscle-tendon compliance is due to a change in the passive properties of the
      muscle fascicles or tendons, or to muscle tears. METHODS: Semimembranosus muscle
      fascicle lengths were measured from ultrasound images obtained from 15 spinal
      cord injured subjects and 20 control subjects while the hip was passively flexed
      with the knee extended. Semimembranosus muscles of spinal cord injured subjects
      were inspected for tears using ultrasound imaging. FINDINGS: The mean (SD) hip
      angle at 30 Nm was 97 (SD 24) degrees in spinal cord injured subjects and 70 (SD
      11) degrees in control subjects, indicating that spinal cord injured subjects had
      very compliant hamstring muscle-tendon units. The ratio of change in fascicle
      length to change in muscle-tendon length was not statistically different between
      spinal cord injured subjects and control subjects: muscle fascicles lengthened by
      0.30 (SD 0.24) mm/mm in spinal cord injured subjects and 0.42 (SD 0.29) mm/mm in
      control subjects. These data were used to show that there was evidence of
      increased tendon compliance of spinal cord injured subjects compared to control
      subjects, but no evidence of increased muscle fascicle compliance. No tears were
      observed in semimembranosus muscles of spinal cord injured subjects.
      INTERPRETATION: The increased hamstring muscle-tendon compliance apparent in some
      spinal cord injured subjects is due, at least in part, to increased tendon
      compliance. There was no evidence that the increased muscle-tendon compliance was
      due to muscle tears.

PMID- 22854005
TI  - Characterization and normal measurements of the left ventricular outflow tract by
      ECG-gated cardiac CT: implications for disorders of the outflow tract and aortic
      valve.
AB  - RATIONALE AND OBJECTIVES: Studies suggest that electrocardiographically gated
      coronary computed tomographic angiography provides a clear definition of the left
      ventricular outflow tract (LVOT), and normal LVOT morphology may not be round, as
      assumed when the continuity equation is applied during echocardiography. The aims
      of this study were to demonstrate the morphology of the LVOT on coronary computed
      tomographic angiography and to establish normal values for LVOT measurements.
      MATERIALS AND METHODS: Two independent readers retrospectively measured anterior
      posterior (AP) and transverse diameters of the LVOT and performed LVOT planimetry
      on coronary computed tomographic angiographic studies of 106 consecutive patients
      with normal aortic valves. RESULTS: Excellent interobserver agreement was
      observed for all measurements (r = 0.78-0.94). The LVOT was ovoid, with a larger
      transverse diameter than AP diameter during diastole and systole (P < .001).
      However, the ratio of AP diameter to transverse diameter was closer to 1.0 during
      systole (P < .001). Mean indexed LVOT area was minimally larger in systole than
      in diastole (P = .01-.04) and was larger in men than in women during diastole (P
      <= .001) and systole (P <= .01). Mean LVOT area indexed to body surface area was
      2.3 +/- 0.5 cm(2)/m(2) in women and 2.6 +/- 0.7 cm(2)/m(2) in men. LVOT area
      demonstrated significant correlation with aortic root diameter. CONCLUSIONS: The
      normal LVOT is ovoid in shape. LVOT is more circular during systole, but the AP
      diameter remains smaller than the transverse diameter throughout the cardiac
      cycle. The oval shape of the LVOT has important implications when LVOT area is
      calculated from LVOT diameters. Normal LVOT area values established in this study
      should facilitate diagnosis of the fixed component of LVOT obstruction.

PMID- 22854006
TI  - Delineation of optic radiation and stria of Gennari on high-resolution phase
      difference enhanced imaging.
AB  - RATIONALE AND OBJECTIVES: Phase difference enhanced (PADRE) imaging technique can
      selectively enhanced the phase difference between the target and surrounding
      tissue. Our purpose is to assess the delineations of the optic radiation and
      primary visual cortex (stria of Gennari) using PADRE. MATERIALS AND METHODS: The
      subjects were 6 healthy volunteers. Axial and coronal high-spatial resolution
      PADRE images were acquired covering the entire optic radiation using a 3T
      magnetic resonance system. Two radiologists evaluated the PADRE and
      susceptibility-weighted imaging (SWI)-like images for the delineation of four
      layers at the optic radiation (tapetum, internal sagittal stratum, external
      sagittal stratum, and adjacent white matter) on the basis of the anatomic
      appearances of the cadaveric specimens stained with Bodian's method and Kluver
      Barrera method. The radiologists also assessed the delineations of the stria of
      Gennari on PADRE and SWI-like images. RESULTS: In all 6 healthy subjects, the
      PADRE images clearly identified the four layers at the optic radiation, as well
      as the stria of Gennari, which were difficult to appreciate in SWI-like images.
      The anatomic appearances of the optic radiation on PADRE images were more similar
      to those seen in the specimens stained with Kluver-Barrera method than with
      Bodian's method. CONCLUSION: The PADRE technique can delineate the four layers at
      the optic radiation and the stria of Gennari; the differences in myelin densities
      can also be enhanced. The PADRE technique may have the potential to reinforce the
      clinical utility of MRI in the diagnosis of diseases that affect the optic
      radiation and primary visual cortex.

PMID- 22854007
TI  - General surgery graduates may be ill prepared to enter rural or community
      surgical practice.
AB  - BACKGROUND: Rural/community surgery presents unique challenges to general
      surgeons. Not only are they required to perform "classic" general surgery
      procedures, but they are also often expected to be competent in other surgical
      disciplines. METHODS: Final-year Canadian-trained residents in general surgery
      were asked to complete the survey. The survey explored chief residents' career
      plans for the following year and whether or not they would independently perform
      various procedures, some general surgical, and others now considered within the
      domain of the subspecialties. RESULTS: Sixty-four residents (71%) completed the
      survey. Twenty percent planned to undertake a rural surgical practice, 17% an
      urban community practice, and 55% had confirmed fellowships. Most residents
      (>90%) expressed comfort with basic general surgical procedures. However,
      residents were less comfortable with subspecialty procedures that are still
      performed by general surgeons in many rural practices. CONCLUSIONS: More than
      half of graduating general surgery residents are choosing subspecialty fellowship
      training over proceeding directly to practice. Those choosing a rural or
      community practice are likely to feel ill prepared to replace existing surgeons.

PMID- 22854008
TI  - Reconstruction of total pelvic exenteration defects with rectus abdominus
      myocutaneous flaps versus primary closure.
AB  - BACKGROUND: Total pelvic exenteration (TPE) is reserved for patients with locally
      invasive and recurrent pelvic malignancies. Complications such as wound
      infections, dehiscence, hernias, abscesses, and fistulas are common after this
      procedure. The purpose of this study was to determine whether tissue transfer to
      the pelvis after TPE decreases wound complications. METHODS: Fifty-three patients
      who underwent TPE between 2004 and 2010 were reviewed. Two groups were
      identified, those who underwent pelvic reconstruction with a vertical rectus
      abdominus myocutaneous flap (n = 17) and those who underwent primary closure (n =
      36). Demographics, clinicopathologic characteristics, and outcomes were compared.
      RESULTS: The 2 groups were similar in demographics and histopathologic
      characteristics. Preoperative and surgical factors including comorbidities,
      nutrition, radiation, surgical times, blood loss, length of stay, and
      complications were similar between the groups. Of the 17 patients undergoing
      vertical rectus abdominus myocutaneous flap placement, complications were seen in
      11 patients (65%), with most of them stemming from flap dehiscence (n = 7).
      CONCLUSIONS: In our study, the transfer of tissue into the pelvis did not
      increase surgical times, blood loss, length of stay, or wound complications.

PMID- 22854009
TI  - Countering beam divergence effects with focused segmented scintillators for high
      DQE megavoltage active matrix imagers.
AB  - The imaging performance of active matrix flat-panel imagers designed for
      megavoltage imaging (MV AMFPIs) is severely constrained by relatively low x-ray
      detection efficiency, which leads to a detective quantum efficiency (DQE) of only
      ~1%. Previous theoretical and empirical studies by our group have demonstrated
      the potential for addressing this constraint through the utilization of thick,
      two-dimensional, segmented scintillators with optically isolated crystals.
      However, this strategy is constrained by the degradation of high-frequency DQE
      resulting from spatial resolution loss at locations away from the central beam
      axis due to oblique incidence of radiation. To address this challenge, segmented
      scintillators constructed so that the crystals are individually focused toward
      the radiation source are proposed and theoretically investigated. The study was
      performed using Monte Carlo simulations of radiation transport to examine the
      modulation transfer function and DQE of focused segmented scintillators with
      thicknesses ranging from 5 to 60 mm. The results demonstrate that, independent of
      scintillator thickness, the introduction of focusing largely restores spatial
      resolution and DQE performance otherwise lost in thick, unfocused segmented
      scintillators. For the case of a 60 mm thick BGO scintillator and at a location
      20 cm off the central beam axis, use of focusing improves DQE by up to a factor
      of ~130 at non-zero spatial frequencies. The results also indicate relatively
      robust tolerance of such scintillators to positional displacements, of up to 10
      cm in the source-to-detector direction and 2 cm in the lateral direction, from
      their optimal focusing position, which could potentially enhance practical
      clinical use of focused segmented scintillators in MV AMFPIs.

PMID- 22854010
TI  - Human beta-defensin-2 and psoriasin, two new innate immunity targets of zinc
      gluconate.
AB  - BACKGROUND: Antimicrobial peptides (AMPs) are a large family of peptides
      implicated in innate immunity, especially in the epidermis. Zinc gluconate has
      been proven to be efficient to treat inflammatory dermatoses, such as acne
      vulgaris. OBJECTIVES: The aim of our work was to determine whether AMPs could be
      new targets of zinc gluconate treatment in inflammatory dermatoses. MATERIAL AND
      METHODS: To test this hypothesis, we used an ex vivo lipopolysaccharide (LPS)
      induced inflammatory skin explant model, with or without zinc gluconate
      pretreatment. We evaluated human beta-defensin-2 (hBD-2), human beta-defensin-4
      (hBD-4) and psoriasin protein expression and release by immunohistochemistry and
      ELISA, as well as the mRNA expression level by quantitative PCR. RESULTS: We
      found that hBD-2 and psoriasin mRNA expression levels and hBD-2 extracellular
      release, but not hBD-4 expression and release, were significantly upregulated by
      zinc gluconate in LPS-stimulated inflammatory skin explants. CONCLUSION: These
      results suggest that hBD-2 and psoriasin may be two main targets of zinc
      gluconate, involved in its anti-inflammatory activity in dermatoses.

PMID- 22854011
TI  - Analgesic placebo treatment perceptions: acceptability, efficacy, and knowledge.
AB  - Current evidence supports the efficacy of placebo analgesia and illustrates that
      patients may be open to placebo use despite uncertainty regarding its mechanisms.
      Debate persists, however, concerning the ethics of placebo treatments. The
      purpose of the present web-based study was to expand upon the empirical
      literature on placebo analgesia ethics and acceptability. Participants (n = 100)
      provided their definition of a placebo and responded to 24 questions addressing
      placebo analgesia perceived knowledge, acceptability, effectiveness, and
      likelihood of placebo use among different health care providers. Results support
      previous research on the effects of placebo on negative mood and health care
      provider attributions, with findings illustrating that negative consequences of
      administration were largely mitigated by a beneficial treatment outcome. Results
      showed that participants conceptualized placebo as predominately inert and were
      mixed regarding interpretations of placebo effectiveness. Though acceptability
      ratings were dependent on the context of placebo administration, participants
      endorsing even moderate placebo acceptability were more open to placebo
      interventions and reported overall more positive treatment outcomes. Participants
      believed that placebos were used differentially among health care providers.
      Additional studies are needed to determine if placebo education can beneficially
      impact perceptions of placebo analgesia knowledge, acceptability, and treatment
      effectiveness. PERSPECTIVE: This study presents an examination of analgesic
      placebo treatment perceived acceptability, efficacy, and knowledge among lay
      individuals. Our findings highlight the importance of assessing placebo
      conceptualizations and treatment perceptions in evaluating placebo ethics-a
      highly relevant finding that informs the clinical use of placebo components in
      managing pain.

PMID- 22854012
TI  - Identification of decorin derived peptides with a zinc dependent anti-myostatin
      activity.
AB  - Decorin is a member of the small leucine-rich proteoglycan family and it is a
      component of the extracellular matrix. Decorin was previously shown to bind
      different molecules, including myostatin, in a zinc-dependent manner. Here, we
      investigated in detail the anti-myostatin activity of decorin and fragments
      thereof. We show that this protein displays in vitro anti-myostatin activities
      with an IC(50) of 2.3 * 10(-8)M. After intramuscular injection of decorin in
      dystrophic mdx and gamma-sarcoglycan(-/-) mice, we observed a significant
      increase of the muscle mass and this effect was maximal 18 days after
      administration. Further, we show that the myostatin-binding site is located in
      the N-terminal domain of decorin. In fact, a peptide encompassing the 31-71
      sequence retains full myostatin binding capacity and intramuscular injection of
      the peptide induces muscle hypertrophy. The evaluation of three additional
      peptides suggests a crucial role of the four cysteines within the conserved
      CX3CXCX6C motif of class I of the small leucine-rich proteoglycans. Altogether,
      our results show that the N-terminal domain of decorin is sufficient for the
      binding to myostatin and they underscore the crucial role for this interaction of
      zinc and the cysteine cluster.

PMID- 22854013
TI  - Temporal window in which exposure to estradiol permanently modifies ovarian
      function causing polycystic ovary morphology in rats.
AB  - OBJECTIVE: To investigate the developmental window in which E(2) exposure
      produces irreversible changes in ovarian function resulting in polycystic ovary.
      DESIGN: Basic experimental study. SETTING: University animal laboratory.
      ANIMAL(S): Thirty Sprague-Dawley rats were administered a single E(2) valerate
      dose (10 mg/kg of weight) at 1, 7, 14, 21, or 30 days of age. Control rats were
      injected with the vehicle at 1 day of age. All rats were sacrificed at 6 months
      of age. INTERVENTION(S): Observation of vaginal opening, estrous cyclicity by
      vaginal smears, and ovarian morphometry in the 6-month-old rat. MAIN OUTCOME
      MEASURE(S): Measurement of ovarian noradrenaline by high-performance liquid
      chromatography coupled with electrochemical detection, serum levels of LH by
      enzyme-linked immunoassay, P, androstenedione, and E(2) by enzyme immunoassay.
      RESULT(S): Rats exposed to E(2) at 1, 7, or 14 days of life did not show estrual
      cycling activity and maintained a polycystic ovary (PCO) condition throughout the
      entirety of the study. However, if the exposure to E(2) occurred after postnatal
      day 21, the PCO-induced condition was reversible. In rats that developed a
      permanent PCO condition, we observed significant effects of E(2) on ovarian
      morphology if exposure occurred on postnatal day 1 and a presumable effect on the
      hypothalamus if the exposure occurred between postnatal days 1 and 14.
      CONCLUSION(S): Our findings suggest that in rats, the most sensitive period for
      the promotion of an irreversible PCO morphology by estrogenic compounds is during
      neonatal early follicular development.

PMID- 22854014
TI  - Endogenous testosterone and cortisol jointly influence reactive aggression in
      women.
AB  - The dual-hormone hypothesis posits that the effect of testosterone on social
      behavior is moderated by cortisol. The present study tested this hypothesis with
      a competitive reactive aggression paradigm in 53 healthy undergraduate women.
      Salivary cortisol and testosterone were assessed at baseline. Participants were
      personally insulted and subsequently given the opportunity to retaliate by
      administering blasts of white noise to the provocateur. Participants were
      randomly assigned to win or lose the aggressive competition. Basal testosterone
      positively predicted reactive aggression and state dominance, but only among
      participants with high concentrations of basal cortisol. The corresponding,
      reverse pattern was found for state submissiveness. Winners also had higher
      concentrations of testosterone than losers following the aggressive competition.
      We discuss the role of heightened reactivity to social provocation as a possible
      explanation for these effects.

PMID- 22854015
TI  - Stress-related thinking predicts the cortisol awakening response and somatic
      symptoms in healthy adults.
AB  - OBJECTIVE: Perseverative cognition (i.e., worry, stress-related thinking) may
      prolong stress-related physiological activation. However, its role within the
      context of the written emotional disclosure paradigm has not been examined. This
      study explored: (1) the effects of stress-related thinking on the cortisol
      awakening response and upper respiratory infection symptoms and; (2) the efficacy
      of two expressive writing interventions on these health outcomes. METHODS:
      Participants were randomly assigned to write about their most stressful life
      experience (using the Guided Disclosure Protocol; n=39) or positive life
      experiences (n=42) or plans for the day (n=41) for 20 min on 3 consecutive days.
      Participants reported the extent to which they thought about their assigned
      writing topic during the study and in the past (event-related thought). Cortisol
      was measured at 0, 15, 30 and 45 min after awakening on 2 consecutive days at
      baseline and 4 weeks post-intervention. Upper respiratory infection (URI)
      symptoms were assessed at baseline, at 4 weeks and at 6 months. RESULTS: Results
      showed that the writing interventions had no beneficial effects on any of the
      outcome measures. However, a significant interaction was found between event
      related thought and condition on the cortisol awakening response at 1 month
      follow-up and URI symptoms at 6 months. Among participants who wrote about
      stressful/traumatic events, higher stress-related thinking during the study
      predicted increased cortisol levels and URI symptoms compared to participants who
      reported low stress-related thinking. DISCUSSION: These findings are broadly
      consistent with Brosschot et al.'s (2006) perseverative cognition hypothesis and
      highlight the importance of ruminative thinking in understanding stress-health
      processes.

PMID- 22854017
TI  - Automated region segmentation on cartridge case base.
AB  - One of the significant problems encountered in criminology studies is the
      successful automated matching of fired cartridge cases, on the basis of the
      characteristic marks left on them by firearms. An intermediate step in the
      solution of this problem is the segmentation of certain regions that are defined
      on the cartridge case base. This paper describes a model-based method that
      performs segmentation of the cartridge case using surface height image of a
      center fire cartridge case base. The proposed method detects the location of the
      cartridge case base center and specific circular contours around it iteratively
      by projecting the problem to a one-dimensional feature space. In addition, the
      firing pin impression region is determined by utilizing an adaptive threshold
      that differentiates impression marks form primer region surface. Letters on the
      cartridge case base are also detected by using surface modeling and adaptive
      thresholding, in order to render the surface comparison operation robust against
      irrelevant surface features. Promising experimental results indicate the
      eligibility of the proposed method to be used for automated cartridge case base
      region segmentation process.

PMID- 22854016
TI  - Identification and characterization of 2,5-dimethoxy-4-nitro-beta-phenethylamine
      (2C-N)--a new member of 2C-series of designer drug.
AB  - The online sale of psychoactive substances, including hallucinogens, is becoming
      a serious problem in many countries. This paper presents and discusses the mass
      spectrometric, infrared spectroscopic and nuclear magnetic resonance
      spectroscopic data of 2,5-dimethoxy-4-nitro-beta-phenethylamine (2C-N), which was
      identified in a powder sample seized by the authorities in 2011 in Poland. The
      molecular mass of 2C-N (226.0954 amu) was confirmed in the LC/ESI-QTOFMS
      experiment. The molecular ion was also observed in the GC-EI/MS spectrum. A
      characteristic set of ions for the parent substance was found using both
      chromatographic methods, and when derivatization with trifuluoroacetic anhydride
      (TFAA) was applied. Two broad dominant bands at 1520 cm(-1) and 1342/1322 cm(-1),
      observed in the FTIR spectrum of 2C-N, originated from the nitro group. NMR
      spectroscopy helped unequivocal elucidation of the structure. The applied
      identification procedure proved to be a powerful tool to determine the structure
      of a new designer drug.

PMID- 22854018
TI  - Chemical speciation and mobilization of copper and zinc in naturally contaminated
      mine soils with citric and tartaric acids.
AB  - A one-step extraction procedure and a leaching column experiment were performed
      to assess the effects of citric and tartaric acids on Cu and Zn mobilization in
      naturally contaminated mine soils to facilitate assisted phytoextraction. A
      speciation modeling of the soil solution and the metal fractionation of soils
      were performed to elucidate the chemical processes that affected metal desorption
      by organic acids. Different extracting solutions were prepared, all of which
      contained 0.01 M KNO(3) and different concentrations of organic acids: control
      without organic acids, 0.5 mM citric, 0.5 mM tartaric, 10 mM citric, 10 mM
      tartaric, and 5 mM citric +5 mM tartaric. The results of the extraction procedure
      showed that higher concentrations of organic acids increased metal desorption,
      and citric acid was more effective at facilitating metal desorption than tartaric
      acid. Metal desorption was mainly influenced by the decreasing pH and the
      dissolution of Fe and Mn oxides, not by the formation of soluble metal-organic
      complexes as was predicted by the speciation modeling. The results of the column
      study reported that low concentrations of organic acids did not significantly
      increase metal mobilization and that higher doses were also not able to mobilize
      Zn. However, 5-10 mM citric acid significantly promoted Cu mobilization (from 1
      mg kg(-1) in the control to 42 mg kg(-1) with 10 mM citric acid) and reduced the
      exchangeable (from 21 to 3 mg kg(-1)) and the Fe and Mn oxides (from 443 to 277
      mg kg(-1)) fractions. Citric acid could efficiently facilitate assisted
      phytoextraction techniques.

PMID- 22854019
TI  - Predicting dioxin-like PCBs soil contamination levels using milk of grazing
      animal as indicator.
AB  - Dioxin-like PCBs (dl-PCBs) are ubiquitous persistent organic pollutants of
      recognized negative effects on human health. Assessing highly polluted areas
      should be an important public health issue. This study proposes to use the milk
      of grazing animals as a bioindicator of dl-PCB contamination in the environment.
      The hypothesis is that milk concentration of dl-PCBs are related to soil
      concentrations of these compounds, and that soils are generally reflective of a
      larger environmental issue of dl-PCB contamination. In this study, we evaluate
      the possibility of predicting soil concentrations using milk of sheep, cows and
      buffalos in a spatial model. For this purpose, samples of soil and milk collected
      in Campania (Italy) were introduced in a GIS platform to perform geostatistical
      analysis for building a simple predictive model. The ordinary least squares
      regressions (OLS) showed a statistically significant correlation (p<0.05) between
      soil and milk contamination. However, this relationship was spatially variable.
      Thus, a geographically weighted regression (GWR) was performed, obtaining R(2)
      values of 0.91, 0.77 and 0.66 for sheep's, buffalo's and cow's milk respectively.
      Assessed the mathematical relationships between the variables, new data was
      introduced to evaluate the performance of the model. Predictions of soil
      contamination with dl-PCBs using sheep's, cow's and buffalo's milk showed a mean
      error of 23%, 25% and 36% respectively. According to these results the sheep's
      milk can be considered the best bioindicator of dl-PCBs contamination among the
      three species. The results of this project evidence the potentialities of the
      proposed approach to assess bioindicator performance in a spatial predictive
      model.

PMID- 22854020
TI  - Electrochemical mineralization of the azo dye Acid Red 29 (Chromotrope 2R) by
      photoelectro-Fenton process.
AB  - The degradation of 100 mL of 244 mg L(-1) of the azo dye Acid Red 29 (AR29) has
      been studied by photoelectro-Fenton (PEF) using an undivided cell containing a
      boron-doped diamond (BDD) anode and an air-diffusion cathode under UVA
      irradiation. The effect of current density, concentration of catalytic Fe(2+) and
      pH on the process was examined. Quick decolorization and almost total
      mineralization were achieved due to the synergistic action of UVA light and
      oxidant hydroxyl radicals formed in the bulk from Fenton's reaction between
      electrogenerated H(2)O(2) at the cathode and added Fe(2+), as well as in the BDD
      surface from water oxidation. Optimum PEF conditions were found for 0.5-1.0 mM
      Fe(2+) and pH 3.0. Comparable electro-Fenton (EF) degradations in the dark
      yielded much poorer mineralization. The decay kinetics of AR29 followed a pseudo
      first-order reaction with similar rate for EF and PEF. The azo dye disappeared
      much more rapidly than solution color, suggesting the formation of colored
      conjugated products with lambda(max) similar to that of AR29. Ion-exclusion HPLC
      allowed the detection and quantification of tetrahydroxy-p-benzoquinone, oxalic,
      oxalacetic, tartronic, tartaric, oxamic, malonic and fumaric acids as
      intermediates in the PEF process. Oxalic acid, accumulated in large extent, was
      quickly destroyed by the efficient photolysis of Fe(III)-oxalate complexes with
      UVA light, whereas tartronic and oxamic acids were the most persistent byproducts
      because of the larger stability of their Fe(III) complexes. The mineralization of
      the initial N of the azo dye yielded NH(4)(+) ion and NO(3)(-) ion in smaller
      proportion.

PMID- 22854021
TI  - Expanding the repertoire of optogenetically targeted cells with an enhanced gene
      expression system.
AB  - Optogenetics has been enthusiastically pursued in recent neuroscience research,
      and the causal relationship between neural activity and behavior is becoming ever
      more accessible. Here, we established knockin-mediated enhanced gene expression
      by improved tetracycline-controlled gene induction (KENGE-tet) and succeeded in
      generating transgenic mice expressing a highly light-sensitive channelrhodopsin-2
      mutant at levels sufficient to drive the activities of multiple cell types. This
      method requires two lines of mice: one that controls the pattern of expression
      and another that determines the protein to be produced. The generation of new
      lines of either type readily expands the repertoire to choose from. In addition
      to neurons, we were able to manipulate the activity of nonexcitable glial cells
      in vivo. This shows that our system is applicable not only to neuroscience but
      also to any biomedical study that requires understanding of how the activity of a
      selected population of cells propagates through the intricate organic systems.

PMID- 22854022
TI  - SERF protein is a direct modifier of amyloid fiber assembly.
AB  - The inherent cytotoxicity of aberrantly folded protein aggregates contributes
      substantially to the pathogenesis of amyloid diseases. It was recently shown that
      a class of evolutionary conserved proteins, called MOAG-4/SERF, profoundly alter
      amyloid toxicity via an autonomous but yet unexplained mode. We show that the
      biological function of human SERF1a originates from its atypical ability to
      specifically distinguish between amyloid and nonamyloid aggregation. This
      inherently unstructured protein directly affected the aggregation kinetics of a
      broad range of amyloidogenic proteins in vitro, while being inactive against
      nonamyloid aggregation. A representative biophysical analysis of the SERF1a:alpha
      synuclein (aSyn) complex revealed that the amyloid-promoting activity resulted
      from an early and transient interaction, which was sufficient to provoke a
      massive increase of soluble aSyn amyloid nucleation templates. Therefore, the
      autonomous amyloid-modifying activity of SERF1a observed in living organisms
      relies on a direct and dedicated manipulation of the early stages in the amyloid
      aggregation pathway.

PMID- 22854023
TI  - Convergent evolution of sodium ion selectivity in metazoan neuronal signaling.
AB  - Ion selectivity of metazoan voltage-gated Na(+) channels is critical for neuronal
      signaling and has long been attributed to a ring of four conserved amino acids
      that constitute the ion selectivity filter (SF) at the channel pore. Yet, in
      addition to channels with a preference for Ca(2+) ions, the expression and
      characterization of Na(+) channel homologs from the sea anemone Nematostella
      vectensis, a member of the early-branching metazoan phylum Cnidaria, revealed a
      sodium-selective channel bearing a noncanonical SF. Mutagenesis and physiological
      assays suggest that pore elements additional to the SF determine the preference
      for Na(+) in this channel. Phylogenetic analysis assigns the Nematostella Na(+)
      selective channel to a channel group unique to Cnidaria, which diverged >540
      million years ago from Ca(2+)-conducting Na(+) channel homologs. The
      identification of Cnidarian Na(+)-selective ion channels distinct from the
      channels of bilaterian animals indicates that selectivity for Na(+) in neuronal
      signaling emerged independently in these two animal lineages.

PMID- 22854024
TI  - CTCF is required for neural development and stochastic expression of clustered
      Pcdh genes in neurons.
AB  - The CCCTC-binding factor (CTCF) is a key molecule for chromatin conformational
      changes that promote cellular diversity, but nothing is known about its role in
      neurons. Here, we produced mice with a conditional knockout (cKO) of CTCF in
      postmitotic projection neurons, mostly in the dorsal telencephalon. The CTCF-cKO
      mice exhibited postnatal growth retardation and abnormal behavior and had defects
      in functional somatosensory mapping in the brain. In terms of gene expression,
      390 transcripts were expressed at significantly different levels between CTCF
      deficient and control cortex and hippocampus. In particular, the levels of 53
      isoforms of the clustered protocadherin (Pcdh) genes, which are stochastically
      expressed in each neuron, declined markedly. Each CTCF-deficient neuron showed
      defects in dendritic arborization and spine density during brain development.
      Their excitatory postsynaptic currents showed normal amplitude but occurred with
      low frequency. Our results indicate that CTCF regulates functional neural
      development and neuronal diversity by controlling clustered Pcdh expression.

PMID- 22854026
TI  - The stigmatization of mental illnesses.

PMID- 22854027
TI  - From sin to science: fighting the stigmatization of mental illnesses.
AB  - Our paper provides an overview of current stigma discourse, the origins and
      nature of the stigma associated with mental illnesses, stigmatization by health
      providers, and approaches to stigma reduction. This is a narrative review
      focusing on seminal works from the social and psychological literature, with
      selected qualitative and quantitative studies and international policy documents
      to highlight key points. Stigma discourse has increasingly moved toward a human
      rights model that views stigma as a form of social oppression resulting from a
      complex sociopolitical process that exploits and entrenches the power imbalance
      between people who stigmatize and those who are stigmatized. People who have a
      mental illness have identified mental health and health providers as key
      contributors to the stigmatization process and worthy targets of antistigma
      interventions. Six approaches to stigma reduction are described: education,
      protest, contact-based education, legislative reform, advocacy, and stigma self
      management. Stigma denigrates the value of people who have a mental illness and
      the social and professional support systems designed to support them. It creates
      inequities in funding and service delivery that undermine recovery and full
      social participation. Mental health professionals have often been identified as
      part of the problem, but they can redress this situation by becoming important
      partners in antistigma work.

PMID- 22854025
TI  - Prognostic impact of vitamin B6 metabolism in lung cancer.
AB  - Patients with non-small cell lung cancer (NSCLC) are routinely treated with
      cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we
      identified vitamin B6 metabolism as a central regulator of cisplatin responses in
      vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the
      depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated
      DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis.
      Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct
      types of physical and chemical stress, including multiple chemotherapeutics. This
      effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive
      form of vitamin B6. In line with a general role of vitamin B6 in stress
      responses, low PDXK expression levels were found to be associated with poor
      disease outcome in two independent cohorts of patients with NSCLC. These results
      indicate that PDXK expression levels constitute a biomarker for risk
      stratification among patients with NSCLC.

PMID- 22854028
TI  - On the self-stigma of mental illness: stages, disclosure, and strategies for
      change.
AB  - People with mental illness have long experienced prejudice and discrimination.
      Researchers have been able to study this phenomenon as stigma and have begun to
      examine ways of reducing this stigma. Public stigma is the most prominent form
      observed and studied, as it represents the prejudice and discrimination directed
      at a group by the larger population. Self-stigma occurs when people internalize
      these public attitudes and suffer numerous negative consequences as a result. In
      our article, we more fully define the concept of self-stigma and describe the
      negative consequences of self-stigma for people with mental illness. We also
      examine the advantages and disadvantages of disclosure in reducing the impact of
      stigma. In addition, we argue that a key to challenging self-stigma is to promote
      personal empowerment. Lastly, we discuss individual- and societal-level methods
      for reducing self-stigma, programs led by peers as well as those led by social
      service providers.

PMID- 22854029
TI  - Evidence-based review of clinical outcomes of guideline-recommended
      pharmacotherapies for generalized anxiety disorder.
AB  - OBJECTIVE: To quantify the rates of clinical outcomes of Canadian Psychiatric
      Association (CPA) guideline-recommended pharmacotherapies for generalized anxiety
      disorder (GAD) by drug classification within each treatment line. METHODS:
      Evidence from original research cited by the CPA was included. Pooled analyses,
      duplicates, and studies with nonextractable data were excluded. Response,
      remission, and baseline-endpoint or mean reductions scores of the Hamilton
      Anxiety Rating Scale (HARS) were extracted. The Cochrane Collaboration's computer
      program, Review Manager, version 5, with a random effects model, was used to pool
      results. RESULTS: A total of 50 articles were cited as evidence for managing GAD
      by the CPA. There was sufficient evidence of remission with first- or third-line
      agents to pool reported rates, and with agents from all 3 treatment lines to pool
      response rates and reduction in HARS scores. The mean range of effect size varied
      considerably from study to study within each treatment line. Comparison of pooled
      remission rates between first- and second-line agents was not possible. While the
      range of values by drug and drug class overlapped, the summary results for the
      probability of response and reduction in HARS scores was greater for first-line,
      compared with second-line, treatments. Drug components for third-line treatments
      were heterogeneous and produced mixed results. CONCLUSION: Despite the abundance
      of evidence in its totality presented in the CPA guidelines, there is inadequate
      evidence to formulate recommendations based on the pooled results from this study
      alone. However, such analysis provides an additional resource for clinicians to
      make more effective treatment decisions for individual patients with GAD.

PMID- 22854030
TI  - Common and unique risk factors and comorbidity for 12-month mood and anxiety
      disorders among Canadians.
AB  - OBJECTIVE: To explore the common and unique risk factors for mood and anxiety
      disorders. What sociodemographic, psychological, and physical risk factors are
      associated with mood and anxiety disorders and their comorbidities? What is the
      impact of multiple risk factors? METHOD: Data from the Canadian Community Health
      Survey: Mental Health and Well-Being were analyzed. Appropriate sampling weights
      and bootstrap variance estimation were employed. Multiple logistic regression was
      used to estimate odds ratios and confidence intervals. RESULTS: The annual
      prevalence of any mood disorder was 5.2%, and of any anxiety disorder 4.7%. Major
      depressive episode was the most prevalent mood and anxiety disorder (4.8%),
      followed by social phobia, panic disorder, mania, and agoraphobia. Among people
      with mood and anxiety disorders, 22.4% had 2 or more disorders. Risk factors
      common to mood and anxiety disorders were being young, having lower household
      income, being unmarried, experiencing greater stress, having poorer mental
      health, and having a medical condition. Unique risk factors were found: major
      depressive episode and social phobia were associated with being born in Canada;
      panic disorder was associated with being Caucasian; lower education was
      associated with panic and agoraphobia; and poor physical health was associated
      with mania and agoraphobia. People who were young, unmarried, not fully employed,
      and had a medical condition, greater stress, poorer self-rated mental health, and
      dissatisfaction with life, were more likely to have a comorbid mood and (or)
      anxiety disorder. As the number of common risk factors increases, the probability
      of having mood and anxiety disorders also increases. CONCLUSIONS: Common and
      unique risk factors exist for mood and anxiety disorders. Risk factors are
      additive in increasing the likelihood of disease.

PMID- 22854031
TI  - The essential and potentially inappropriate use of antipsychotics across income
      groups: an analysis of linked administrative data.
AB  - OBJECTIVE: To examine the essential and potentially inappropriate use of
      antipsychotics across income groups. METHOD: Linked health, pharmaceutical use,
      and income data from British Columbia were analyzed to examine antipsychotic use
      in 2 study cohorts. In the first cohort, the essential use of antipsychotics was
      assessed among adults who had a recorded diagnosis of schizophrenia in a 2-year
      period, 2004-2005. In the second cohort, potentially inappropriate use of
      antipsychotics was examined in people with no recorded diagnosis of schizophrenia
      or bipolar disorders in 2004-2005. The second cohort was also composed
      exclusively of seniors with a dementia-related diagnosis who are either in long
      term care or living in the community. Income-related differences in antipsychotic
      use in these 2 cohorts were assessed using logistic regression, controlling for
      health and sociodemographic characteristics known to influence medicine use.
      RESULTS: Among adults, the prevalence of essential antipsychotic use was high
      (85%), with higher odds of use evident among those in the middle-income group.
      Among seniors, the prevalence of potentially inappropriate antipsychotic
      treatment is 23%, with prevalence higher in long-term care (56%) than in the
      community (13%). No income-related differences were found in long-term care;
      however, in the community, higher odds of use were found in low-income seniors.
      CONCLUSION: People from low-income households have slightly lower levels of
      essential antipsychotic use and are more likely to receive potentially
      inappropriate antipsychotic treatment.

PMID- 22854032
TI  - Examining the association between psychiatric illness and suicidal ideation in a
      sample of treatment-seeking Canadian peacekeeping and combat veterans with
      posttraumatic stress disorder PTSD.
AB  - OBJECTIVE: Our study examines the association between suicidal ideation and and
      self-reported symptoms of posttraumatic stress disorder (PTSD), major depressive
      disorder (MDD), generalized anxiety disorder (GAD), and alcohol use disorder
      (AUD) in a sample of treatment-seeking Canadian combat and peacekeeping veterans;
      and identifies potential predictors of suicidal ideation. METHODS: Actively
      serving Canadian Forces and Royal Canadian Mounted Police members and veterans
      seeking treatment at the Parkwood Hospital Operational Stress Injury Clinic (n =
      250) completed measures including the Primary Care Evaluation of Mental Disorders
      Patient Health Questionnaire, the Alcohol Use Disorder Identification Test, and
      the PTSD Checklist-Military Version (PCL-M) between January 2002 and December
      2010. Regression analyses were used to determine the respective impact of PTSD,
      and self-reported symptoms of MDD, GAD, AUD, and anxiety on suicidal ideation.
      RESULTS: Most people met PCL-M screening criteria for PTSD (73.6%, n = 184),
      while 70.8% (n = 177) screened positively for a probable major depressive
      episode. PTSD symptom was significantly associated with suicidal ideation (beta =
      0.412, P < 0.001). After controlling for self-reported depressive symptom
      severity, AUD severity, and generalized anxiety, PTSD severity was no longer
      significantly associated with suicidal ideation (beta = 0.043, P = 0.58).
      CONCLUSIONS: Although PTSD alone is associated with suicidal ideation, after
      controlling for common comorbid psychiatric illnesses, self-reported depressive
      symptom severity emerged as the most significant predictor of suicidal ideation.
      These findings support the importance of screening for comorbidities,
      particularly an MDD, as potentially modifiable conditions that are strongly
      related to suicidal ideation in military personnel's endorsing criteria for PTSD.

PMID- 22854033
TI  - Forty-five-year mortality rate as a function of the number and type of
      psychiatric diagnoses found in a large Danish birth cohort.
AB  - OBJECTIVE: Psychiatric comorbidities are common among psychiatric patients and
      typically associated with poorer clinical prognoses. Subjects of a large Danish
      birth cohort were used to study the relation between mortality and co-occurring
      psychiatric diagnoses. METHOD: We searched the Danish Central Psychiatric
      Research Registry for 8109 birth cohort members aged 45 years. Lifetime
      psychiatric diagnoses (International Classification of Diseases, Revision 10,
      group F codes, Mental and Behavioural Disorders, and one Z code) for identified
      subjects were organized into 14 mutually exclusive diagnostic categories.
      Mortality rates were examined as a function of number and type of co-occurring
      diagnoses. RESULTS: Psychiatric outcomes for 1247 subjects were associated with
      157 deaths. Early mortality risk in psychiatric patients correlated with the
      number of diagnostic categories (Wald chi2 = 25.0, df = 1, P < 0.001). This
      global relation was true for anxiety and personality disorders, but not for
      schizophrenia and substance abuse, which had intrinsically high mortality rates
      with no comorbidities. CONCLUSIONS: Risk of early mortality among psychiatric
      patients appears to be a function of both the number and the type of psychiatric
      diagnoses.

PMID- 22854034
TI  - Neuroleptic malignant syndrome-an 11-year longitudinal case-control study.
AB  - OBJECTIVE: To describe patients with neuroleptic malignant syndrome (NMS), to
      establish occurrence of NMS, to investigate risk factors of NMS, and to
      investigate mortality associated with NMS. METHOD: We conducted a longitudinal
      register linkage case-control study of NMS. RESULT: In health care registers
      covering the period from 1996 to 2007, we identified, among 224 372 patients with
      organic, psychotic, affective, or neurotic diagnosis, 83 patients with NMS,
      equivalent to an occurrence of 0.04%. Treatment with second-generation
      antipsychotics (SGAs) in the 3 months preceding admission increased the NMS risk
      (OR 4.66; 95% CI 1.96 to 11.10) and also first-generation antipsychotics (FGAs)
      of high potency (OR 23.41; 95% CI 5.29 to 103.61) and mid potency (OR 4.81; 95%
      CI 1.96 to 11.79), and depot antipsychotics (OR 4.53; 95% CI 1.60 to 12.80).
      Benzodiazepines (BDZs) also increased the risk of NMS (OR 3.43; 95% CI 1.68 to
      12.80). NMS was associated with an increased mortality (HR 1.88; 95% CI 1.19 to
      2.98) in patients, compared with sex-, age-, and diagnosis-matched control
      subjects, but no significant difference in mortality between patients and control
      subjects was observed after the initial 30 days (P = 0.27). CONCLUSIONS: The
      occurrence of NMS is low, and the prediction of NMS is difficult. Previous
      treatment with FGAs, SGAs, and BDZs was identified as a risk factor for
      developing NMS. NMS increased mortality within 30 days after NMS.

PMID- 22854036
TI  - Diffusion MRI signal reconstruction with continuity constraint and optimal
      regularization.
AB  - In diffusion MRI, the reconstruction of the full Ensemble Average Propagator
      (EAP) provides new insights in the diffusion process and the underlying
      microstructure. The reconstruction of the signal in the whole Q-space is still
      extremely challenging however. It requires very long acquisition protocols, and
      robust reconstruction to cope with the very low SNR at large b-values. Several
      reconstruction methods were proposed recently, among which the Spherical Polar
      Fourier (SPF) expansion, a promising basis for signal reconstruction. Yet the
      reconstruction in SPF is still subject to noise and discontinuity of the
      reconstruction. In this work, we present a method for the reconstruction of the
      diffusion attenuation in the whole Q-space, with a special focus on continuity
      and optimal regularization. We derive a modified Spherical Polar Fourier (mSPF)
      basis, orthonormal and compatible with SPF, for the reconstruction of a signal
      with continuity constraint. We also derive the expression of a Laplace
      regularization operator in the basis, together with a method based on generalized
      cross validation for the optimal choice of the parameter. Our method results in a
      noticeable dimension reduction as compared with SPF. Tested on synthetic and real
      data, the reconstruction with this method is more robust to noise and better
      preserves fiber directions and crossings.

PMID- 22854035
TI  - Vectorization of optically sectioned brain microvasculature: learning aids
      completion of vascular graphs by connecting gaps and deleting open-ended
      segments.
AB  - A graph of tissue vasculature is an essential requirement to model the exchange
      of gasses and nutriments between the blood and cells in the brain. Such a graph
      is derived from a vectorized representation of anatomical data, provides a map of
      all vessels as vertices and segments, and may include the location of nonvascular
      components, such as neuronal and glial somata. Yet vectorized data sets typically
      contain erroneous gaps, spurious endpoints, and spuriously merged strands.
      Current methods to correct such defects only address the issue of connecting gaps
      and further require manual tuning of parameters in a high dimensional algorithm.
      To address these shortcomings, we introduce a supervised machine learning method
      that (1) connects vessel gaps by "learned threshold relaxation"; (2) removes
      spurious segments by "learning to eliminate deletion candidate strands"; and (3)
      enforces consistency in the joint space of learned vascular graph corrections
      through "consistency learning." Human operators are only required to label
      individual objects they recognize in a training set and are not burdened with
      tuning parameters. The supervised learning procedure examines the geometry and
      topology of features in the neighborhood of each vessel segment under
      consideration. We demonstrate the effectiveness of these methods on four sets of
      microvascular data, each with >800(3) voxels, obtained with all optical histology
      of mouse tissue and vectorization by state-of-the-art techniques in image
      segmentation. Through statistically validated sampling and analysis in terms of
      precision recall curves, we find that learning with bagged boosted decision trees
      reduces equal-error error rates for threshold relaxation by 5-21% and strand
      elimination performance by 18-57%. We benchmark generalization performance across
      datasets; while improvements vary between data sets, learning always leads to a
      useful reduction in error rates. Overall, learning is shown to more than halve
      the total error rate, and therefore, human time spent manually correcting such
      vectorizations.

PMID- 22854037
TI  - HoliMAb: a holistic approach for Media-Adventitia border detection in
      intravascular ultrasound.
AB  - We present a fully automatic methodology for the detection of the Media
      Adventitia border (MAb) in human coronary artery in Intravascular Ultrasound
      (IVUS) images. A robust border detection is achieved by means of a holistic
      interpretation of the detection problem where the target object, i.e. the media
      layer, is considered as part of the whole vessel in the image and all the
      relationships between tissues are learnt. A fairly general framework exploiting
      multi-class tissue characterization as well as contextual information on the
      morphology and the appearance of the tissues is presented. The methodology is (i)
      validated through an exhaustive comparison with both Inter-observer variability
      on two challenging databases and (ii) compared with state-of-the-art methods for
      the detection of the MAb in IVUS. The obtained averaged values for the mean
      radial distance and the percentage of area difference are 0.211 mm and 10.1%,
      respectively. The applicability of the proposed methodology to clinical practice
      is also discussed.

PMID- 22854039
TI  - FGD1 as a central regulator of extracellular matrix remodelling--lessons from
      faciogenital dysplasia.
AB  - Disabling mutations in the FGD1 gene cause faciogenital dysplasia (also known as
      Aarskog-Scott syndrome), a human X-linked developmental disorder that results in
      disproportionately short stature, facial, skeletal and urogenital anomalies, and
      in a number of cases, mild mental retardation. FGD1 encodes the guanine
      nucleotide exchange factor FGD1, which is specific for the Rho GTPase cell
      division cycle 42 (CDC42). CDC42 controls cytoskeleton-dependent membrane
      rearrangements, transcriptional activation, secretory membrane trafficking, G1
      transition during the cell cycle and tumorigenic transformation. The cellular
      mechanisms by which FGD1 mutations lead to the hallmark skeletal deformations of
      faciogenital dysplasia remain unclear, but the pathology of the disease, as well
      as some recent discoveries, clearly show that the protein is involved in the
      regulation of bone development. Two recent studies unveiled new potential
      functions of FGD1, in particular, its involvement in the regulation of the
      formation and function of invadopodia and podosomes, which are cellular
      structures devoted to degradation of the extracellular matrix in tumour and
      endothelial cells. Here, we discuss the hypothesis that FGD1 might be an
      important regulator of events controlling extracellular matrix remodelling and
      possibly cell invasion in physiological and pathological settings. Additionally,
      we focus on how studying the cell biology of FGD1 might help us to connect the
      dots that link CDC42 signalling with remodelling of the extracellular matrix
      (ECM) in physiology and complex diseases, while, at the same time, furthering our
      understanding of the pathogenesis of faciogenital dysplasia.

PMID- 22854038
TI  - Polo-like kinase is required for synaptonemal complex disassembly and
      phosphorylation in mouse spermatocytes.
AB  - During meiosis, accurate coordination of the completion of homologous
      recombination and synaptonemal complex (SC) disassembly during the prophase to
      metaphase I (G2/MI) transition is essential to avoid aneuploid gametes and
      infertility. Previous studies have shown that kinase activity is required to
      promote meiotic prophase exit. The first step of the G2/MI transition is the
      disassembly of the central element components of the SC; however, the kinase(s)
      required to trigger this process remains unknown. Here we assess roles of polo
      like kinases (PLKs) in mouse spermatocytes, both in vivo and during prophase exit
      induced ex vivo by the phosphatase inhibitor okadaic acid. All four PLKs are
      expressed during the first wave of spermatogenesis. Only PLK1 (not PLK2-4)
      localizes to the SC during the G2/MI transition. The SC central element proteins
      SYCP1, TEX12 and SYCE1 are phosphorylated during the G2/MI transition. However,
      treatment of pachytene spermatocytes with the PLK inhibitor BI 2536 prevented the
      okadaic-acid-induced meiotic prophase exit and inhibited phosphorylation of the
      central element proteins as well as their removal from the SC. Phosphorylation
      assays in vitro demonstrated that PLK1, but not PLK2-4, phosphorylates central
      element proteins SYCP1 and TEX12. These findings provide mechanistic details of
      the first stage of SC disassembly in mammalian spermatocytes, and reveal that PLK
      mediated phosphorylation of central element proteins is required for meiotic
      prophase exit.

PMID- 22854040
TI  - Optineurin mediates a negative regulation of Rab8 by the GTPase-activating
      protein TBC1D17.
AB  - Rab GTPases regulate various membrane trafficking pathways but the mechanisms by
      which GTPase-activating proteins recognise specific Rabs are not clear. Rab8 is
      involved in controlling several trafficking processes, including the trafficking
      of transferrin receptor from the early endosome to the recycling endosome. Here,
      we provide evidence to show that TBC1D17, a Rab GTPase-activating protein,
      through its catalytic activity, regulates Rab8-mediated endocytic trafficking of
      transferrin receptor. Optineurin, a Rab8-binding effector protein, mediates the
      interaction and colocalisation of TBC1D17 with Rab8. A non-catalytic region of
      TBC1D17 is required for direct interaction with optineurin. Co-expression of
      Rab8, but not other Rabs tested, rescues the inhibition of transferrin receptor
      trafficking by TBC1D17. The activated GTP-bound form of Rab8 is localised to the
      tubules emanating from the endocytic recycling compartment. Through its catalytic
      activity, TBC1D17 inhibits recruitment of Rab8 to the tubules and reduces
      colocalisation of transferrin receptor and Rab8. Knockdown of optineurin or
      TBC1D17 results in enhanced recruitment of Rab8 to the tubules. A glaucoma
      associated mutant of optineurin, E50K, causes enhanced inhibition of Rab8 by
      TBC1D17, resulting in defective endocytic recycling of transferrin receptor. Our
      results show that TBC1D17, through its interaction with optineurin, regulates
      Rab8-mediated endocytic recycling of transferrin receptor and recruitment of Rab8
      to the endocytic recycling tubules. We describe a mechanism of regulating a Rab
      GTPase by an effector protein (optineurin) that acts as an adaptor to bring
      together a Rab (Rab8) and its GTPase-activating protein (TBC1D17).

PMID- 22854041
TI  - A novel protein complex, Mesh-Ssk, is required for septate junction formation in
      the Drosophila midgut.
AB  - Septate junctions (SJs) are specialized intercellular junctions that restrict the
      free diffusion of solutes through the paracellular route in invertebrate
      epithelia. In arthropods, two morphologically different types of SJs have been
      reported: pleated SJs and smooth SJs (sSJs), which are found in ectodermally and
      endodermally derived epithelia, respectively. However, the molecular and
      functional differences between these SJ types have not been fully elucidated.
      Here, we report that a novel sSJ-specific component, a single-pass transmembrane
      protein, which we term 'Mesh' (encoded by CG31004), is highly concentrated in
      Drosophila sSJs. Compromised mesh expression causes defects in the organization
      of sSJs, in the localizations of other sSJ proteins, and in the barrier function
      of the midgut. Ectopic expression of Mesh in cultured cells induces cell-cell
      adhesion. Mesh forms a complex with Ssk, another sSJ-specific protein, and these
      proteins are mutually interdependent for their localization. Thus, a novel
      protein complex comprising Mesh and Ssk has an important role in sSJ formation
      and in intestinal barrier function in Drosophila.

PMID- 22854042
TI  - Cofactor-dependent maturation of mammalian sulfite oxidase links two
      mitochondrial import pathways.
AB  - Sulfite oxidase (SO) catalyses the metabolic detoxification of sulfite to sulfate
      within the intermembrane space of mitochondria. The enzyme follows a complex
      maturation pathway, including mitochondrial transport and processing, integration
      of two prosthetic groups, molybdenum cofactor (Moco) and heme, as well as
      homodimerisation. We have identified the sequential and cofactor-dependent
      maturation steps of SO. The N-terminal bipartite targeting signal of SO was
      required but not sufficient for mitochondrial localization. In the absence of
      Moco, most of the SO, although processed by the inner membrane peptidase of
      mitochondria, was found in the cytosol. Moco binding was required to induce
      mitochondrial trapping and retention, thus ensuring unidirectional translocation
      of SO. In the absence of the N-terminal targeting sequence, SO assembled in the
      cytosol, suggesting an important function for the leader sequence in preventing
      premature cofactor binding. In vivo, heme binding and dimerisation did not occur
      in the absence of Moco and only occurred after Moco integration. In conclusion,
      the identified molecular hierarchy of SO maturation represents a novel link
      between the canonical presequence pathway and folding-trap mechanisms of
      mitochondrial import.

PMID- 22854043
TI  - Functional involvement of Rab1A in microtubule-dependent anterograde melanosome
      transport in melanocytes.
AB  - Melanosomes are transported to the cell periphery of melanocytes by coordination
      between bidirectional microtubule-dependent movements and unidirectional actin
      dependent movement. Although both the mechanism of the actin-dependent melanosome
      transport and the mechanism of the microtubule-dependent retrograde melanosome
      transport in mammalian skin melanocytes have already been determined, almost
      nothing is known about the mechanism of the microtubule-dependent anterograde
      melanosome transport. Small GTPase Rab proteins are common regulators of membrane
      traffic in all eukaryotes, and in this study we performed genome-wide screening
      for Rab proteins that are involved in anterograde melanosome transport by
      expressing 60 different constitutive active (and negative) mutants, and succeeded
      in identifying Rab1A, originally described as a Golgi-resident Rab, as a prime
      candidate. Endogenous Rab1A protein was found to be localized to mature
      melanosomes in melanocytes, and its functional ablation either by siRNA-mediated
      knockdown or by overexpression of a cytosolic form of Rab1A-GTPase-activating
      protein/TBC1D20 induced perinuclear melanosome aggregation. The results of time
      lapse imaging further revealed that long-range anterograde melanosome movements
      were specifically suppressed in Rab1A-deficient melanocytes, whereas retrograde
      melanosome transport occurred normally. Taken together, these findings indicate
      that Rab1A is the first crucial component of the anterograde melanosome transport
      machinery to be identified in mammalian skin melanocytes.

PMID- 22854044
TI  - Real-time hyperspectral fluorescence imaging of pancreatic beta-cell dynamics
      with the image mapping spectrometer.
AB  - The development of multi-colored fluorescent proteins, nanocrystals and organic
      fluorophores, along with the resulting engineered biosensors, has revolutionized
      the study of protein localization and dynamics in living cells. Hyperspectral
      imaging has proven to be a useful approach for such studies, but this technique
      is often limited by low signal and insufficient temporal resolution. Here, we
      present an implementation of a snapshot hyperspectral imaging device, the image
      mapping spectrometer (IMS), which acquires full spectral information
      simultaneously from each pixel in the field without scanning. The IMS is capable
      of real-time signal capture from multiple fluorophores with high collection
      efficiency (~65%) and image acquisition rate (up to 7.2 fps). To demonstrate the
      capabilities of the IMS in cellular applications, we have combined fluorescent
      protein (FP)-FRET and [Ca(2+)](i) biosensors to measure simultaneously
      intracellular cAMP and [Ca(2+)](i) signaling in pancreatic beta-cells.
      Additionally, we have compared quantitatively the IMS detection efficiency with a
      laser-scanning confocal microscope.

PMID- 22854045
TI  - The conserved kinase SRPK regulates karyosome formation and spindle microtubule
      assembly in Drosophila oocytes.
AB  - In Drosophila oocytes, after the completion of recombination, meiotic chromosomes
      form a compact cluster called the karyosome within the nucleus, and later
      assemble spindle microtubules without centrosomes. Although these oocyte-specific
      phenomena are also observed in humans, their molecular basis is not well
      understood. Here, we report essential roles for the conserved kinase SRPK in both
      karyosome formation and spindle microtubule assembly in oocytes. We have
      identified a female-sterile srpk mutant through a cytological screen for
      karyosome defects. Unlike most karyosome mutants, the karyosome defect is
      independent of the meiotic recombination checkpoint. Heterochromatin clustering
      found within the wild-type karyosome is disrupted in the mutant. Strikingly, a
      loss of SRPK severely prevents microtubule assembly for acentrosomal spindles in
      mature oocytes. Subsequently, bi-orientation and segregation of meiotic
      chromosomes are also defective. Therefore, this study demonstrates new roles of
      this conserved kinase in two independent meiotic steps specific to oocytes.

PMID- 22854047
TI  - S-glutathionylation of LMW-PTP regulates VEGF-mediated FAK activation and
      endothelial cell migration.
AB  - Although promising, the ability to regulate angiogenesis through delivery of VEGF
      remains an unrealized goal. We have shown previously that physiological levels of
      peroxynitrite (1 uM) are required for a VEGF-mediated angiogenic response, yet
      the redox-regulated mechanisms that govern the VEGF signal remain unexplored. We
      assessed the impact of VEGF and peroxynitrite on modifying redox-state, the level
      of reduced-glutathione (GSH) and S-glutathionylation on regulation of the low
      molecular weight protein tyrosine phosphatase (LMW-PTP) and focal adhesion kinase
      (FAK), which are key mediators of VEGF-mediated cell migration. Stimulation of
      human microvascular endothelial (HME) cells with VEGF (20 ng/ml) or peroxynitrite
      (1 uM) caused an immediate and reversible negative-shift in the cellular redox
      state and thiol oxidation of LMW-PTP, which culminated in cell migration. VEGF
      causes reversible S-glutathionylation of LMW-PTP, which inhibits its
      phosphorylation and activity, and causes the transient activation of FAK.
      Modulating the redox-state using decomposing peroxynitrite (FeTPPS, 2.5 uM) or
      the GSH-precursor [N-acetylcysteine (NAC), 1 mM] caused a positive-shift of the
      redox-state and prevented VEGF-mediated S-glutathionylation and oxidative
      inhibition of LMW-PTP. NAC and FeTPPS prevented the activation of FAK, its
      association with LMW-PTP and cell migration. Inhibiting LMW-PTP expression
      markedly enhanced FAK activation and cell migration. Although mild oxidative
      stress achieved by combining VEGF with 0.1-0.2 mM peroxynitrite augmented cell
      migration, an acute shift to oxidative stress achieved by combining VEGF with 0.5
      mM peroxynitrite induced and sustained FAK activation, and LMW-PTP S
      glutathionylation, resulting in LMW-PTP inactivation and inhibited cell
      migration. In conclusion, our findings demonstrate that a balanced redox-state is
      required for VEGF to facilitate reversible S-glutathionylation of LMW-PTP, FAK
      activation and endothelial cell migration. Shifting the redox-state to reductive
      stress or oxidative stress inhibited the VEGF-mediated angiogenic response.

PMID- 22854046
TI  - Limitation of individual folding resources in the ER leads to outcomes distinct
      from the unfolded protein response.
AB  - ER stress leads to upregulation of multiple folding and quality control
      components, known as the unfolded protein response (UPR). Glucose Regulated
      Protein 78 (GRP78) (also known as binding immunoglobulin protein, BiP, and HSPA5)
      and GRP94 are often upregulated coordinately as part of this homeostatic
      response. Given that endoplasmic reticulum (ER) chaperones have distinct sets of
      clients, we asked how cells respond to ablation of individual chaperones. The
      cellular responses to silencing BiP, GRP94, HSP47, PDIA6 and OS-9, were distinct.
      When BiP was silenced, a widespread UPR was observed, but when GRP94 was either
      inhibited or depleted by RNA interference (RNAi), the expression of only some
      genes was induced, notably those encoding BiP and protein disulfide isomerase A6
      (PDIA6). Silencing of HSP47 or OS-9 did not lead to any compensatory induction of
      other genes. The selective response to GRP94 depletion was distinct from a
      typical ER stress response, both because other UPR target genes were not affected
      and because the canonical UPR signaling branches were not activated. The response
      to silencing of GRP94 did not preclude further UPR induction when chemical stress
      was imposed. Importantly, re-expression of wild-type GRP94 in the silenced cells
      prevented the upregulation of BiP and PDIA6, whereas re-expression of an ATPase
      deficient GRP94 mutant did not, indicating that cells monitor the activity state
      of GRP94. These findings suggest that cells are able to distinguish among folding
      resources and generate distinct responses.

PMID- 22854048
TI  - Kruppel-like factor 4 is involved in cell scattering induced by hepatocyte growth
      factor.
AB  - Hepatocyte growth factor/scatter factor (HGF) is unique by inducing epithelial
      cell scattering, a cellular event pivotal to HGF-mediated invasive-growth
      response essential for embryonic development and metastasis. Kruppel-like factor
      4 (KLF4) is a multifunctional zinc-finger transcription factor involved in cell
      proliferation, differentiation and self-renewal. We herein present the first
      evidence for the functional connection between KLF4 and HGF-induced cell
      scattering. In particular, we found that KLF4 was upregulated by HGF in two
      independent epithelial cell types, HepG2 and MDCK, whereas KLF4 knockdown
      inhibited HGF-induced E-cadherin suppression and cell scattering. Moreover,
      enforced nuclear KLF4 expression alone was sufficient to upregulate KLF4,
      downregulate E-cadherin and trigger scattering. Chromatin immunoprecipitation
      (ChIP) analysis further revealed that KLF4 induced suppression of E-cadherin
      transcription by directly binding to the E-cadherin promoter. Additionally, we
      proved that HGF-induced upregulation of KLF4 transcription and cell scattering
      require activation of the MEK/ERK signaling pathway and the induction of early
      growth response 1 (EGR-1). At the mechanistic level, ChIP analysis validated a
      direct binding of EGR-1 to the KLF4 promoter to induce KLF4 transcription; in
      turn, EGR-1-induced KLF4 binds to its own promoter, thus creating a positive
      feedback mechanism to sustain KLF4 expression and the resultant cell scattering.
      We conclude that KLF4 upregulation by HGF represents a novel mechanism mediating
      HGF-induced cell scattering and perhaps other associated events such as cell
      migration and invasion.

PMID- 22854049
TI  - Measuring carotid intima-media thickness: simple protocols have advantages.

PMID- 22854051
TI  - Severe hypocalcemia following denosumab injection in a hemodialysis patient.
AB  - Denosumab is a human monoclonal antibody directed against RANKL (receptor
      activator of NF-kappaB ligand) and is a novel treatment for postmenopausal
      osteoporosis, although its safety and efficacy in end-stage renal disease is
      unclear. We report the case of a 61-year-old female hemodialysis patient who
      developed severe hypocalcemia (total serum calcium, 5.37 mg/dL [1.34 mmol/L])
      after receiving a single subcutaneous injection of denosumab. We review this
      medication's mechanism of action and the very limited data regarding its use in
      stage 5 chronic kidney disease. We advise against the use of denosumab in those
      treated with hemodialysis due to the risk of severe hypocalcemia and lack of
      evidence supporting its efficacy in treating osteoporosis in this population.

PMID- 22854052
TI  - Dying other, dying self: creating culture and meaning in palliative healthcare.
AB  - Dying is an act of creativity, and we each die as cultural beings. Culture helps
      us create the meaning death requests of us. However, the dominant culture of the
      healthcare system views death as a failure of modern medicine, an event of
      unspeakable terror and taboo. Palliative clinicians must honor each dying
      person's cultural identity (as well as the person's family), not subject it to
      the dominant discourse of Western medicine. This article offers practical
      guidelines for palliative clinicians to do so, as well as a case vignette. 

PMID- 22854050
TI  - Activated HER-receptors in predicting outcome of ER-positive breast cancer
      patients treated with adjuvant endocrine therapy.
AB  - The four human epidermal growth factor receptors (HER1-4) are involved in growth
      stimulation and may play a role in endocrine resistance. The receptors form
      dimers, leading to activation by mutual phosphorylation. Our purpose was to
      explore the role of the activated receptors (pHER1, pHER2, pHER3) in endocrine
      treated breast cancer in terms of co-expression and association with disease-free
      survival (DFS) in 1062 patients with ER-positive tumors. Furthermore, HER2
      amplification was evaluated. We found positive associations between the
      phosphorylated receptors. pHER1 and pHER3 were co-expressed with one or two of
      the other activated receptors in 85% and 89% of tumors, respectively, whereas
      pHER2 was co-expressed with the other activated receptors in 54% of tumors.
      Except for HER2, which was associated with poor prognosis, none of the remaining
      markers were associated with DFS. However, frequent co-expression indicates a
      role of the other HER-family members in activation of HER2.

PMID- 22854053
TI  - Infundibular cyst with seborrheic verruca-like cyst walls in a patient with Yusho
      disease exposed to dioxins.

PMID- 22854054
TI  - Nasal and paranasal sinus anatomical variations in patients with rhinogenic
      contact point headache.
AB  - OBJECTIVE: To define anatomical variations that may lead to rhinogenic contact
      point headache. METHODS: Paranasal sinuses CT scan and medical records of sixty
      five patients who underwent a successful endoscopic surgery for rhinogenic
      contact point headache reviewed. RESULTS: Eleven distinct anatomical variations
      were found in patients with rhinogenic contact point headache. All of them were
      surgically curable. CONCLUSION: There are multiple anatomical situations that may
      lead to rhinogenic contact point headache and each one has its own
      characteristics. Treatment plan should be personalized for every patient
      considering the diagnosed anatomical variation.

PMID- 22854055
TI  - Cochlear implantation in a patient with Epstein syndrome.
AB  - Epstein syndrome is a rare disease which is accompanied by nephritis,
      sensorineural hearing impairment and macrothrombocytopenia. It has been suggested
      that this syndrome is a hereditary disease associated with mutations in MYH9,
      which encodes non-muscle myosin heavy chain IIA. We report a case of a patient
      with Epstein syndrome in whom bilateral profound hearing impairment developed and
      who had undergone cochlear implantation 9 years previously. Prior to this, the
      patient showed progressive sensorineural hearing impairment and had become
      completely deaf by the age of 25. A cochlear implant was successfully used with a
      speech discrimination score of 98% (sentence test). However, in the present case,
      peri- and postoperative complications occurred: tympanic perforation remained
      after a promontory stimulation test, followed by transitory otitis with purulent
      discharge. Therefore, tympanoplasty was performed simultaneously with cochlear
      implantation. These complications were considered to be caused by platelet
      dysfunction and delayed wound healing. Furthermore, cochlear destruction was
      observed 8 years postoperatively. In Epstein syndrome, the mechanism of osseous
      change remains uncertain. To the best of our knowledge, this is the first case
      report of Epstein syndrome in a patient with long-term use of a CI.

PMID- 22854056
TI  - Laterally attached superior turbinate is associated with opacification of the
      sphenoid sinus.
AB  - OBJECTIVE: The sphenoid sinus is situated at the most posterior part of the nasal
      cavity and opens at the sphenoethmoidal recess located between the nasal septum
      and the superior turbinate. The correlation between anatomical structures
      surrounding the sphenoid sinus and sphenoid sinusitis is poorly understood. This
      study investigated possible factors that correlate to opacification of the
      sphenoid sinus on computed tomography. METHODS: Review of computed tomography
      images of 200 patients who underwent endoscopic sinus surgery and/or septoplasty.
      The total lengths of the anterior sphenoid wall and the part medial to the
      superior turbinate were measured. The correlations were analyzed between the
      occurrence of sphenoiditis and these values, as well as age, sex, presence or
      absence of Onodi cell, opacification of the paranasal sinuses other than the
      sphenoid sinus, and shadow at the olfactory cleft. RESULTS: The length of the
      part medial to the superior turbinate was significantly (odds ratio=1.36,
      P=0.001) associated with sphenoiditis, but the total length of the anterior wall
      of the sphenoid was not. Advanced age and disease of the olfactory cleft,
      posterior ethmoid cells, and frontal sinus were also correlated with
      sphenoiditis. CONCLUSIONS: Certain characteristics of the anatomical structures
      surrounding the sphenoid sinus are associated with sphenoiditis.

PMID- 22854057
TI  - Ethical implications of research on craving.
AB  - Cravings, intense desires to experience the effects of a drug, are widely
      regarded as significant impediments to overcoming addiction, although their role
      in relapse may be overstated. Scientists and clinicians wish to better understand
      the neurobiological and cognitive basis of craving so that they may develop
      psychotherapeutic, pharmacological and other medical methods to reduce craving
      and thereby drug use. The conduct of such research raises significant ethical
      issues. When recruiting individuals and conducting this research, scientists need
      to ensure that substance dependent participants have the capacity to provide free
      and uncoerced consent. This is especially the case in studies in which dependent
      participants are given their drug of addiction or provided with other inducements
      to participate (e.g. financial incentives) that may undermine their ability to
      fully consider the risks of participation. Treatments for addiction that seek to
      reduce cravings may also carry risks. This includes psychotherapeutic approaches,
      as well as pharmacological and medical treatments. Clinicians need to consider
      the risks and benefits of treatment and carefully communicate these to patients.
      The desire to reduce urges to use drugs should not be employed to justify
      potentially harmful and ineffective treatments. The safety and effectiveness of
      emerging treatments should be assessed by well conducted randomized controlled
      clinical trials.

PMID- 22854058
TI  - Submucosal endoscopy with mucosal resection: a hybrid endoscopic submucosal
      dissection in the porcine rectum and distal colon.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has appeal for en bloc
      resection of large flat colorectal polyps but carries appreciable risk and
      demands a high level of expertise and training. Undermining flat and laterally
      spreading colorectal polyps by using submucosal endoscopy with the mucosal safety
      valve flap (SEMF) may be combined with ESD to offer a hybrid technique that is
      easier and safer. OBJECTIVE: To determine the feasibility of combining SEMF and
      ESD for the removal of progressively larger areas of the mucosa in the porcine
      rectum and colon. DESIGN: Two-phase ex vivo and in vivo study using domestic pig
      rectum and distal colon. SETTING: Developmental endoscopy unit/animal research
      unit. INTERVENTIONS: Progressively larger targeted mucosal dissections were
      performed by using the basic principles of ESD, which included margination of the
      targeted area of mucosa, submucosal fluid cushion, and needle-knife dissection.
      These were combined with the SEMF method of predissection with carbon dioxide
      (CO(2)) gas and balloon-based blunt dissection of the submucosa undermining the
      targeted and isolated mucosa. The hybrid technique was first applied to ex vivo
      porcine rectums and distal colons, then in vivo in an acute animal study.
      Progressively larger staged dissections were performed with 2-, 4-, and 6-cm
      diameter targeted mucosal sites. MAIN OUTCOME MEASUREMENTS: Success with
      associated difficulty or failure of the hybrid method in the rectum and distal
      colon to achieve complete resection of a progressively larger targeted area of
      mucosa. RESULTS: The ex vivo phase of the experiment demonstrated the ability to
      use the blunt balloon dissection of the SEMF procedure to remove 2-, 4-, and 6-cm
      areas of rectum and distal colon with a rapid progression to the largest size
      resection. The colon proximal to 20 cm above the anus was unable to hold a
      submucosal fluid cushion and allow submucosal dissection. Successful hybrid ESD
      was performed in vivo with staged progression through to the largest mucosal area
      (6 cm) within 20 cm of the anus. Dissections became progressively easier and
      faster to perform and dependent on the following steps: a traditional
      circumferential mucosal incision into the deep submucosa, an initial needle-knife
      submucosal "tunnel" dissection above the muscularis propria (MP), balloon
      dissection, and needle-knife release of persistent tethering strands of submucosa
      with and without vessels. Of 16 hybrid resections, 3 failures and 2 very
      difficult resections were attributed to attempts at resection too proximal in the
      colon, excessive flexibility of the balloon catheter, and electrosurgical device
      subperformance. There were no mucosal perforations or coagulation injuries to the
      MP. A single uninflated balloon catheter perforation of the MP occurred in a
      dissection site just above 20 cm from the anus with a suboptimal fluid cushion.
      LIMITATIONS: Animal study. Procedures performed by a single endoscopist with long
      standing familiarity with the SEMF method. CONCLUSIONS: Large mucosal target
      sites in the rectum and distal colon of the pig can be safely removed en bloc by
      means of a hybrid technique, ie, submucosal endoscopy with mucosal resection,
      combining elements of ESD with our SEMF method.

PMID- 22854059
TI  - Endoscopic deployment of video capsule endoscopy: does it guarantee a complete
      examination of the small bowel?

PMID- 22854060
TI  - Diagnostic accuracy of quantitative EUS elastography for discriminating malignant
      from benign solid pancreatic masses: a prospective, single-center study.
AB  - BACKGROUND: Recent data suggest that quantitative EUS elastography, a novel
      technique that allows real-time quantification of tissue stiffness, can
      accurately differentiate malignant from benign solid pancreatic masses.
      OBJECTIVE: To externally validate the diagnostic utility of this technique in an
      independent cohort. DESIGN AND SETTING: Prospective, single-center study.
      PATIENTS, INTERVENTIONS, AND METHODS: A total of 104 patients with evidence of a
      solid pancreatic mass on cross-sectional imaging and/or endosonography underwent
      111 quantitative EUS elastography procedures. Multiple elastographic measurements
      of the mass lesion and soft-tissue reference areas were undertaken, and the
      corresponding strain ratios (SRs) were calculated. The final diagnosis was based
      on pancreatic cytology or histology. MAIN OUTCOME MEASUREMENTS: The area under
      the receiver-operating characteristic curve, sensitivity, specificity, positive
      predictive value, negative predictive value, and overall accuracy of quantitative
      EUS elastography for discriminating malignant from benign pancreatic masses.
      RESULTS: The final diagnoses were primary pancreatic carcinoma (71.2%),
      neuroendocrine tumor (10.6%), metastatic cancer (1.9%), and pancreatitis (16.3%).
      Malignant masses had a higher SR (P = .01) and lower mass elasticity (P = .003)
      than inflammatory ones. The areas under the receiver-operating characteristic
      curve for the detection of pancreatic malignancy of both SR and mass elasticity
      (0.69 and 0.72, respectively) were less favorable than reported recently. At the
      cut points providing the highest accuracy in this cohort (4.65 for SR and 0.27%
      for mass elasticity), quantitative EUS elastography had a sensitivity of 100.0%
      and 95.7%, specificity of 16.7% and 22.2%, positive predictive value of 86.1% and
      86.4%, negative predictive value of 100.0% and 50.0%, and overall accuracy of
      86.5% and 83.8%, respectively. LIMITATIONS: Relatively small number of patients
      with benign disease. CONCLUSION: In the largest single-center study to date, the
      diagnostic utility of quantitative EUS elastography for discriminating pancreatic
      masses was modest, suggesting that it may only supplement rather than supplant
      the role of pancreatic tissue sampling in the future.

PMID- 22854061
TI  - Efficacy of peripheral blood stem cell transplantation versus conventional
      chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64
      patients from a single center.
AB  - Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting
      adverse factors at diagnosis. Many groups believed aggressive treatment
      strategies such as autologous stem cell transplantation brought survival benefit
      for ALCL patients. However, few compared these approaches with conventional
      chemotherapy to validate their superiority. Here, we report a study comparing the
      efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional
      chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were
      studied retrospectively. The median follow-up period was 51 months (range, 1-167
      months). For 48 patients undergoing conventional chemotherapy only, the 4-year
      event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%,
      respectively. Altogether, 16 patients underwent PBSCT, including 11 at first
      remission (CR1/PR1), 3 at second remission, and 2 with disease progression during
      first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT
      at first remission were 81.8% and 90.9%, respectively. Compared with conventional
      chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS
      (P = 0.580) when applied at first remission. Univariate analysis showed that
      patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky
      disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P =
      0.059), and age <= 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT
      significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P =
      0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front
      strategy. Based on these results, we conclude that, for patients with specific
      adverse factors such as B symptoms and bulky disease, PBSCT was superior to
      conventional chemotherapy in terms of EFS.

PMID- 22854062
TI  - Metaplastic carcinoma of the right breast and simultaneous giant ovarian
      teratoma: a case report.
AB  - We describe here a female patient who presented with a breast mass and giant
      abdominal mass. Fine needle aspiration cytology of the breast mass and
      histological examination after modified radical mastectomy confirmed metaplastic
      carcinoma of the breast. The epithelial components were formed by infiltrating
      ductal carcinoma with poor differentiation, and the sarcomatous components were
      formed by fibrosarcoma and osteosarcoma. Histological examination of the
      abdominal mass confirmed ovarian teratoma. The patient underwent modified radical
      mastectomy of the right breast and laparoscopic excision of the abdominal mass in
      the lower right quadrant. Having underwent six courses of chemotherapy, the
      patient is now in her tenth month after surgery and under follow-up, and she has
      no relapsed disease. These two diseases have never seen in one patient before.
      The case we report here provides some new data for research and clinical
      experience and it may also provide a new insight into the relationship between
      metaplastic breast carcinoma and ovarian teratoma.

PMID- 22854063
TI  - Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1).
AB  - A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously
      known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2
      that is required for cellular resistance against DNA interstrand crosslinking
      (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here,
      we provide evidence that FAN1 is degraded during mitotic exit, suggesting that
      FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex
      (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level
      of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation
      of FAN1 affected the progression to mitotic exit. Collectively, these data
      suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key
      role during mitotic exit.

PMID- 22854064
TI  - Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for
      clinical target volume delineation.
AB  - Clinical target volume (CTV) delineation is crucial for tumor control and normal
      tissue protection. This study aimed to define the locoregional extension patterns
      of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic
      resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed.
      According to incidence rates of tumor invasion, the anatomic sites surrounding
      the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and
      low-risk (<5%) groups. The lymph node (LN) level was determined according to the
      Radiation Therapy Oncology Group guidelines, which were further categorized into
      the upper neck (retropharyngeal region and level II), middle neck (levels III and
      Va), and lower neck (levels IV and Vb and the supraclavicular fossa). The high
      risk anatomic sites were adjacent to the nasopharynx, whereas those at medium-or
      low-risk were separated from the nasopharynx. If the high-risk anatomic sites
      were involved, the rates of tumor invasion into the adjacent medium-risk sites
      increased; if not, the rates were significantly lower (P<0.01). Among the 1920
      (81.1%) patients with positive LN, the incidence rates of LN metastasis in the
      upper, middle, and lower neck were 99.6%, 30.2%, and 7.2%, respectively, and skip
      metastasis happened in only 1.2% of patients. In the 929 patients who had
      unilateral upper neck involvement, the rates of contralateral middle neck and
      lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease
      spreads stepwise from proximal sites to distal sites, and LN metastasis spreads
      from the upper neck to the lower neck. Individualized CTV delineation for NPC may
      be feasible.

PMID- 22854066
TI  - Scintigraphic assessment of salivary function after intensity-modulated
      radiotherapy for head and neck cancer: correlations with parotid dose and quality
      of life.
AB  - OBJECTIVE: We investigated salivary function using quantitative scintigraphy and
      sought to identify functional correlations between parotid dose and quality of
      life (QoL) for head and neck cancer (HNC) patients receiving intensity-modulated
      radiotherapy (IMRT). MATERIALS AND METHODS: Between August, 2007 and June, 2008,
      31 patients treated IMRT for HNC were enrolled in this prospective study.
      Salivary excretion function (SEF) was previously measured by salivary
      scintigraphy at annual intervals for 2 years after IMRT. A dose-volume histogram
      of each parotid gland was calculated, and the normal tissue complication
      probability (NTCP) was used to determine the tolerance dose. QoL was
      longitudinally assessed by the EORTC QLQ-C30 and H&N35 questionnaires prior to
      RT, and at one, three, 12 and 24 months after RT. RESULTS: A significant
      correlation was found between the reduction of SEF and the mean parotid dose
      measured at 1 year (correlation coefficient, R(2)=0.651) and 2 years (R(2)=0.310)
      after IMRT (p<0.001). The TD(50) of the parotid gland at 1 year after IMRT is
      43.6 Gy, comparable to results from western countries. We further found that
      contralateral parotid and submandibular gland function preservation was
      correlated with reduced sticky saliva and a better QoL compared to the functional
      preservation of both parotid glands, as determined by the EORTC QLQ-H&N35
      questionnaire. CONCLUSION: A significant correlation was found between the
      reduction of SEF and the mean parotid dose. Preservation of contralateral parotid
      and submandibular gland function predicts a better QoL compared to preservation
      of the function of both parotid glands.

PMID- 22854065
TI  - Role of autophagy in acute myeloid leukemia therapy.
AB  - Despite its dual role in determining cell fate in a wide array of solid cancer
      cell lines, autophagy has been robustly shown to suppress or kill acute myeloid
      leukemia cells via degradation of the oncogenic fusion protein that drives
      leukemogenesis. However, autophagy also induces the demise of acute leukemia
      cells that do not express the known fusion protein, though the molecular
      mechanism remains elusive. Nevertheless, since it can induce cooperation with
      apoptosis and differentiation in response to autophagic signals, autophagy can be
      manipulated for a better therapy on acute myeloid leukemia.

PMID- 22854067
TI  - Passenger strand miRNA miR-31* regulates the phenotypes of oral cancer cells by
      targeting RhoA.
AB  - OBJECTIVES: MicroRNAs (miRNAs) are endogenous small non-coding RNAs that
      negatively regular target gene expression by RNA interference. The processing of
      the pre-miRNA hairpin generates a miRNA duplex, which consists of a miRNA (guide
      strand) and a miRNA(*) (passenger strand). miR-31 is an oncogenic miRNA and is up
      regulated in oral squamous cell carcinoma (OSCC). miR-31(*) shows a high level of
      conservation across species and, based on this, this study hypothesized that miR
      31(*) is a functional miRNA. MATERIALS AND METHODS: The expression of miR-31 and
      miR-31* in OSCC tissues and oral cells were analyzed. Functional studies were
      performed on OSCC cells. RESULTS: miR-31(*) is up-regulated in OSCC tissues, but
      its expression is less abundant than miR-31. miR-31(*) decreases the
      proliferation and migration of both SAS and Fadu cells. Furthermore, miR-31(*)
      targets the 3'UTR of RhoA and is able to down-regulate RhoA expression. Knockdown
      of RhoA expression is known to decrease the proliferation and migration of OSCC
      cells. However, up-regulation of both miR-31 and miR-31(*) by delivery of pre-mir
      31 does still enhance OSCC oncogenicity. CONCLUSION: miR-31(*) is a functional
      miRNA involving in regulating RhoA, and the activity of miR-31(*)'s activity
      seems to counteract the functions of miR-31 during OSCC tumorigenesis.

PMID- 22854068
TI  - Wilderness medical society practice guidelines for the prevention and treatment
      of lightning injuries.
AB  - To provide guidance to clinicians about best practices, the Wilderness Medical
      Society convened an expert panel to develop evidence-based guidelines for the
      treatment and prevention of lightning injuries. These guidelines include a review
      of the epidemiology of lightning strikes and recommendations for the prevention
      of lightning strikes, along with treatment recommendations organized by organ
      system. Recommendations are graded based on the quality of supporting evidence
      according to criteria put forth by the American College of Chest Physicians.

PMID- 22854070
TI  - [Osteoporosis and oral diseases].
AB  - Osteoporosis is a major cause of fractures in elderly women. Bone densitometry is
      used in order to detect osteoporosis. It has been observed can also be analyzed
      in the jawbone. The osteoporosis may be associated with resorption of the
      residual ridge, periodontitis and tooth loss; also the same treatments can affect
      the jaws. A search was carried out in the Medline-Pubmed database in order to
      search the association between osteoporosis and oral diseases over the past 5
      years. Forty-two articles were obtained after the selection process. The authors
      stated that: in reference to periodontal disease the results are conflicting, but
      there seems to be a higher prevalence of the disease and tooth loss and
      resorption of the crest. Oral bisphosphonates have little risk of causing
      osteonecrosis, and there is no relationship in the dental implant failure among
      patients taking bisphosphonates. There is no clear scientific evidence that could
      link osteoporosis and oral diseases.

PMID- 22854069
TI  - Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an
      examination of shared genetic and environmental effects.
AB  - BACKGROUND: Previous studies examined caffeine use and caffeine dependence and
      risk for the symptoms, or diagnosis, of psychiatric disorders. The current study
      aimed to determine if generalized anxiety disorder (GAD), panic disorder,
      phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia
      nervosa (BN) shared common genetic or environmental factors with caffeine use,
      caffeine tolerance, or caffeine withdrawal. METHOD: Using 2,270 women from the
      Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate
      Cholesky decomposition models were used to determine if any of the psychiatric
      disorders shared genetic or environmental factors with caffeine use phenotypes.
      RESULTS: GAD, phobias, and MDD shared genetic factors with caffeine use, with
      genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal
      of the shared genetic and environmental parameter for phobias and caffeine use
      resulted in a significantly worse fitting model. MDD shared unique environmental
      factors (environmental correlation=0.23) with caffeine tolerance; the genetic
      correlation between AN and caffeine tolerance and BN and caffeine tolerance were
      0.64 and 0.49, respectively. Removal of the genetic and environmental correlation
      parameters resulted in significantly worse fitting models for GAD, phobias, MDD,
      AN, and BN, which suggested that there was significant shared liability between
      each of these phenotypes and caffeine tolerance. GAD had modest genetic
      correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35.
      CONCLUSIONS: There was suggestive evidence of shared genetic and environmental
      liability between psychiatric disorders and caffeine phenotypes. This might
      inform us about the etiology of the comorbidity between these phenotypes.

PMID- 22854072
TI  - Nest predation risk and growth strategies of passerine species: grow fast or
      develop traits to escape risk?
AB  - Different body components are thought to trade off in their growth and
      development rates, but the causes for relative prioritization of any trait
      remains a critical question. Offspring of species at higher risk of predation
      might prioritize development of locomotor traits that facilitate escaping risky
      environments over growth of mass. We tested this possibility in 12 altricial
      passerine species that differed in their risk of nest predation. We found that
      rates of growth and development of mass, wings, and endothermy increased with
      nest predation risk across species. In particular, species with higher nest
      predation risk exhibited relatively faster growth of wings than of mass, fledged
      with relatively larger wing sizes and smaller mass, and developed endothermy
      earlier at relatively smaller mass. This differential development can facilitate
      both escape from predators and survival outside of the nest environment. Tarsus
      growth was not differentially prioritized with respect to nest predation risk,
      and instead all species achieved adult tarsus size by age of fledging. We also
      tested whether different foraging modes (aerial, arboreal, and ground foragers)
      might explain the variation of differential growth of locomotor modules, but we
      found that little residual variation was explained. Our results suggest that
      differences in nest predation risk among species are associated with relative
      prioritization of body components to facilitate escape from the risky nest
      environment.

PMID- 22854071
TI  - [Serum lactate in the emergency department as a prognostic factor in patients
      with sepsis without hypotension].
AB  - BACKGROUND AND OBJECTIVE: The relationship between lactate and mortality in
      patients without hypotension has not been appropriately explored. Our aim was to
      determine the usefulness of serum lactate as a prognostic factor of 28-day
      mortality in patients admitted to the Emergency Department with clinical
      diagnosis of sepsis without septic shock. PATIENTS AND METHODS: We performed a
      secondary analysis of the study The epidemiology of sepsis in Colombia, a
      prospective cohort of patients from 10 general hospitals in 4 Colombian cities.
      We analyzed patients without hypotension with serum lactate available and
      admitted with community-acquired infections, which were confirmed according to
      the Centers for Disease Control and Prevention CDC criteria. A logistical
      regression was performed adjusting for age, sex, comorbidities and severity
      scores. RESULTS: We included 961 patients aged 57.2 +/- 21.0 years, 54.2% were
      females, mean SOFA score was 3.0 +/- 2.3 and APACHE score was 11.1+/-6.4. We
      observed a linear relationship between serum lactate and the odds of death, and
      after adjustment there was a significant and independent association between
      lactate and mortality (odds ratio 1,16, 95% confidence interval 1.02-1.33).
      CONCLUSION: Serum lactate is independently and significantly associated with 28
      day mortality among patients with infection who present to the Emergency
      Department without hypotension. Besides, mortality increases in a linear way with
      serum lactate from any detectable value.

PMID- 22854073
TI  - Synergy and group size in microbial cooperation.
AB  - Microbes produce many molecules that are important for their growth and
      development, and the exploitation of these secretions by nonproducers has
      recently become an important paradigm in microbial social evolution. Although the
      production of these public-goods molecules has been studied intensely, little is
      known of how the benefits accrued and the costs incurred depend on the quantity
      of public-goods molecules produced. We focus here on the relationship between the
      shape of the benefit curve and cellular density, using a model assuming three
      types of benefit functions: diminishing, accelerating, and sigmoidal
      (accelerating and then diminishing). We classify the latter two as being
      synergistic and argue that sigmoidal curves are common in microbial systems.
      Synergistic benefit curves interact with group sizes to give very different
      expected evolutionary dynamics. In particular, we show that whether and to what
      extent microbes evolve to produce public goods depends strongly on group size. We
      show that synergy can create an "evolutionary trap" that can stymie the
      establishment and maintenance of cooperation. By allowing density-dependent
      regulation of production (quorum sensing), we show how this trap may be avoided.
      We discuss the implications of our results on experimental design.

PMID- 22854074
TI  - Reciprocal interaction matrix reveals complex genetic and dose-dependent
      specificity among coinfecting parasites.
AB  - Understanding genetic specificity in factors determining the outcome of host
      parasite interactions is especially important as it contributes to parasite
      epidemiology, virulence, and maintenance of genetic variation. Such specificity,
      however, is still generally poorly understood. We examined genetic specificity in
      interactions among coinfecting parasites. In natural populations, individual
      hosts are often simultaneously infected by multiple parasite species and
      genotypes that interact. Such interactions could maintain genetic variation in
      parasite populations if they are genetically specific so that the relative
      fitness of parasite genotypes varies across host individuals depending on (1) the
      presence/absence of coinfections and/or (2) the genetic composition of the
      coinfecting parasite community. We tested these predictions using clones of fish
      eye flukes Diplostomum pseudospathaceum and Diplostomum gasterostei. We found
      that interactions among parasites had a strong genetic basis and that this
      modified genetic variation in infection success of D. pseudospathaceum between
      single and multiple infections as well as across multiply infected host
      individuals depending on the genetic identity of the coinfecting D. gasterostei.
      The relative magnitude of these effects, however, depended on the exposure dose,
      suggesting that ecological factors can modify genetic interactions between
      parasites.

PMID- 22854075
TI  - A meta-analysis of community response predictability to anthropogenic
      disturbances.
AB  - Disturbances often lead to changes in average values of community properties;
      however, disturbances can also affect the predictability of a community's
      response. We performed a meta-analysis to determine how response predictability,
      defined as among-replicate variance in diversity and community abundance, is
      affected by species removals, species invasions, nutrient addition, temperature
      increase, and habitat loss/fragmentation, and we further determined whether
      response predictability differed according to habitat and trophic role. Species
      removals and nutrient addition decreased response predictability, while species
      invasions increased response predictability. In aquatic habitats, disturbances
      generally led to a decrease in response predictability, whereas terrestrial
      habitats showed no overall change in response predictability, suggesting that
      differences in food web and ecosystem structure affect how communities respond to
      disturbance. Producers were also more likely to show decreases in response
      predictability, particularly following species removals, highlighting widespread
      destabilizing effects of species loss at the producer level. Overall, our results
      show that whether disturbances cause changes in response predictability is highly
      contingent on disturbance type, habitat, and trophic role. The nature of changes
      in response predictability--for example, strong decreases following species
      invasions and increases following species removals--will likely play a major role
      in how communities recover from disturbance.

PMID- 22854076
TI  - Evolution of novel mosaic castes in ants: modularity, phenotypic plasticity, and
      colonial buffering.
AB  - Many ants have independently evolved castes with novel morphology as well as
      function, such as soldiers and permanently wingless (ergatoid) queens. We present
      a conceptual model, based on modularity in morphology and development, in which
      evolutionary innovation is facilitated by the ancestral ant polyphenism of winged
      queens and wingless workers. We suggest that novel castes evolved from rare
      intercastes, anomalous mosaics of winged queens and workers, erratically produced
      by colonies through environmental or genetic perturbations. The colonial
      environment is highly accommodating and buffers viable intercastes from
      individual selection. Their cost is limited because they are diluted by the large
      number of nestmates, yet some can bring disproportionate benefits to their
      colonies in the context of defense or reproduction (e.g., wingless intercastes
      able to mate). Useful intercastes will increase in frequency as their morphology
      is stabilized through genetic accommodation. We show that both soldiers and
      ergatoid queens are mosaics of winged queens and workers, and they are strikingly
      similar to some intercastes. Modularity and developmental plasticity together
      with winged/wingless polyphenism thus allow for the production of highly variable
      mosaic intercastes, and colonies incubate the advantageous mosaics.

PMID- 22854077
TI  - Fitness effects of floral plasticity and thermoregulation in a thermally changing
      environment.
AB  - To better understand the evolution of phenotypic plasticity and thermoregulation
      and their potential value for ectotherms in the face of global warming, we
      conducted field experiments to measure their effects on fitness and their
      association with reproductive phenology in Plantago lanceolata in a thermally
      variable environment. We measured the reproductive timing and success of
      genotypes varying in thermoregulation, as mediated by floral-reflectance
      plasticity. Results were consistent with the hypothesis that thermoregulation is
      more adaptive when thermally variable reproductive seasons are shorter and
      cooler. Strong thermoregulation/plasticity increased reproductive success during
      the cool portion of the reproductive season but not during the warm portion.
      Directional selection that favored strongly thermoregulating genotypes early in
      the season shifted to stabilizing selection that favored genotypes with weaker
      thermoregulation later in the season. Thermoregulation and reproductive phenology
      were negatively correlated. Although reproductive onset and duration were similar
      between genotypes, strong thermoregulators produced more and larger spikes
      (clutches) early; weak thermoregulators produced more spikes late. Results
      suggest that with atmospheric warming, the benefit of raising body temperature
      via thermoregulation when it is cool should decline in extant populations. The
      negative correlation between thermoregulation and phenology should accelerate the
      evolutionary shift toward thermoconformity, that is, reduced plasticity.

PMID- 22854078
TI  - Don't put all your eggs in one nest: spread them and cut time at risk.
AB  - In many egg-laying animals, some females spread their clutch among several nests.
      The fitness effects of this reproductive tactic are obscure. Using mathematical
      modeling and field observations, we analyze an unexplored benefit of egg
      spreading in brood parasitic and other breeding systems: reduced time at risk for
      offspring. If a clutch takes many days to lay until incubation and embryo
      development starts after the last egg, by spreading her eggs a parasitic female
      can reduce offspring time in the vulnerable nest at risk of predation or other
      destruction. The model suggests that she can achieve much of this benefit by
      spreading her eggs among a few nests, even if her total clutch is large. Field
      data from goldeneye ducks Bucephala clangula show that egg spreading enables a
      fecund female to lay a clutch that is much larger than average without increasing
      offspring time at risk in a nest. This advantage increases with female condition
      (fecundity) and can markedly raise female reproductive success. These results
      help explain the puzzle of nesting parasites in some precocial birds, which lay
      eggs in the nests of other females before laying eggs in their own nest. Risk
      reduction by egg spreading may also play a role in the evolution of other
      breeding systems and taxa-for instance, polyandry with male parental care in some
      birds and fishes.

PMID- 22854079
TI  - Previous experience and contest outcome: winner effects persist in absence of
      evident loser effects in a parasitoid wasp.
AB  - The experience of a previous conflict can affect animals' performance during a
      later contest: a victory usually increases and a defeat usually decreases the
      probability of winning a subsequent conflict. These winner and loser effects
      could result from a reassessment by contestants of their perceived fighting
      abilities. Game-theoretic models based on this assumption predict that a loser
      effect can exist alone or in the presence of a winner effect, but a winner effect
      cannot persist alone, at least when contestants are young and without experience
      of contest. Moreover, when both effects coexist, the loser effect is expected to
      be of a greater magnitude and last longer than the winner effect. To date, these
      predictions have been supported by empirical evidence. Here we show for the first
      time that a winner effect can exist in the absence of any evident loser effect in
      a parasitoid wasp, Eupelmus vuilleti, when fighting for hosts. This finding
      consequently raises questions about the possible mechanisms involved and
      challenges the main assumption of previous theoretical models. We suggest an
      alternative explanation for the evolution of only winner effects that is based on
      the modification of contestants' subjective value of the resource rather than on
      a reestimation of their fighting abilities.

PMID- 22854080
TI  - Stochastic population dynamics and life-history variation in marine fish species.
AB  - We examined whether differences in life-history characteristics can explain
      interspecific variation in stochastic population dynamics in nine marine fish
      species living in the Barents Sea system. After observation errors in population
      estimates were accounted for, temporal variability in natural mortality rate,
      annual recruitment, and population growth rate was negatively related to
      generation time. Mean natural mortality rate, annual recruitment, and population
      growth rate were lower in long-lived species than in short-lived species. Thus,
      important species-specific characteristics of the population dynamics were
      related to the species position along the slow-fast continuum of life-history
      variation. These relationships were further associated with interspecific
      differences in ecology: species at the fast end were mainly pelagic, with short
      generation times and high natural mortality, annual recruitment, and population
      growth rates, and also showed high temporal variability in those demographic
      traits. In contrast, species at the slow end were long-lived, deepwater species
      with low rates and reduced temporal variability in the same demographic traits.
      These interspecific relationships show that the life-history characteristics of a
      species can predict basic features of interspecific variation in population
      dynamical characteristics of marine fish, which should have implications for the
      choice of harvest strategy to facilitate sustainable yields.

PMID- 22854081
TI  - Revisiting Santa Rosalia to unfold a degeneracy of classic models of speciation.
AB  - Many classic models of speciation incorporate assortative mating based on mating
      groups, such as plants with different flowering times, and they investigate
      whether an ecological trait under disruptive natural selection becomes
      genetically associated with the selectively neutral mating trait. It is well
      known that this genetic association is potently destroyed by recombination. In
      this note, we point out a more fundamental difficulty: if a "knife-edge" symmetry
      assumption of previous models is violated, then the mating trait is no longer
      neutral and sexual selection eliminates the polymorphism in the mating locus.
      This result strengthens the growing consensus that magic traits are the more
      likely route to nonallopatric speciation. We expand the model assuming also
      ecological selection on the mating trait and investigate the conditions for
      natural selection to overcome sexual selection and maintain mating polymorphism;
      we find that the combination of natural and sexual selection can cause also
      bistability of allele frequencies.

PMID- 22854082
TI  - Extracting the underlying physiological determinants of resource-based trade
      offs: a principal components approach.
AB  - The relationship between traits that compete for resources is influenced by
      variance in the acquisition and allocation of resources. The difficulty of
      accurately measuring these underlying physiological processes has hampered
      studies of resource-based trade-offs. Here, we explore the ability of principal
      components analysis (PCA) to extract axes corresponding to acquisition and
      allocation in a bivariate trade-off by comparing these axes to estimates obtained
      using physiological measurements. We validate the method using simulations and
      then test it using empirical data for the well-characterized trade-off between
      flight capability and reproduction in female sand crickets, Gryllus firmus. We
      find a high correspondence between our physiological estimates and the estimates
      obtained using PCA. Our results demonstrate that PCA provides a robust and
      efficient method for estimating acquisition and allocation directly from the
      traits involved in a resource-based trade-off.

PMID- 22854085
TI  - Ontogeny tends to recapitulate phylogeny in digital organisms.
AB  - Biologists have long debated whether ontogeny recapitulates phylogeny and, if so,
      why. Two plausible explanations are that (i) changes to early developmental
      stages are selected against because they tend to disrupt later development and
      (ii) simpler structures often precede more complex ones in both ontogeny and
      phylogeny if the former serve as building blocks for the latter. It is difficult
      to test these hypotheses experimentally in natural systems, so we used a
      computational system that exhibits evolutionary dynamics. We observed that
      ontogeny does indeed recapitulate phylogeny; traits that arose earlier in a
      lineage's history also tended to be expressed earlier in the development of
      individuals. The relative complexity of traits contributed substantially to this
      correlation, but a significant tendency toward recapitulation remained even after
      accounting for trait complexity. This additional effect provides evidence that
      selection against developmental disruption also contributed to the conservation
      of early stages in development.

PMID- 22854086
TI  - Diversity partitioning confirms the importance of beta components in tropical
      rainforest Lepidoptera.
AB  - Tropical beta diversity, and particularly that of herbivorous insects in
      rainforests, is often considered to be enormous, but this notion has recently
      been challenged. Because tropical beta diversity is highly relevant to our view
      on biodiversity, it is important to gain more insights and to resolve
      methodological problems that may lead to contradictions in different studies. We
      used data on two ecologically distinct moth families from Southeast Asia and
      analyzed separately the contribution of beta components to overall species
      richness at three spatial scales. Observed diversity partitions were compared
      under different types of null models. We found that alpha diversity was lower
      than expected on the basis of null models, whereas hierarchical beta components
      were larger than expected. Beta components played a significant role in shaping
      gamma diversity, and their contribution can be high (multiplicative beta >5). We
      found a reduction in beta components when comparing primary forests to
      agricultural sites (cf. "biotic homogenization"), but even in these habitats,
      beta components were still substantial. Our analyses show that beta components do
      play an important role in our data on tropical herbivorous insects and that these
      results are not attributable to lumping different habitats when sampling
      environmental gradients.

PMID- 22854087
TI  - Reduced bacterial biodiversity is associated with increased allergy.

PMID- 22854088
TI  - Nitrate dynamics in agricultural catchments deduced from groundwater dating and
      long-term nitrate monitoring in surface- and groundwaters.
AB  - Although nitrate export in agricultural catchments has been simulated using
      various types of models, the role of groundwater in nitrate dynamics has rarely
      been fully taken into account. We used groundwater dating methods (CFC analyses)
      to reconstruct the original nitrate concentrations in the groundwater recharge in
      Brittany (Western France) from 1950 to 2009. This revealed a sharp increase in
      nitrate concentrations from 1977 to 1990 followed by a slight decrease. The
      recharge concentration curve was then compared with past chronicles of
      groundwater concentration. Groundwater can be interpreted as resulting from the
      annual dilution of recharge water in an uncontaminated aquifer. Two aquifers were
      considered: the weathered aquifer and the deeper fractured aquifer. The nitrate
      concentrations observed in the upper part of the weathered aquifer implied an
      annual renewal rate of 27 to 33% of the reservoir volume while those in the lower
      part indicated an annual renewal rate of 2-3%. The concentrations in the deep
      fractured aquifer showed an annual renewal rate of 0.1%. The river concentration
      can be simulated by combining these various groundwater reservoirs with the
      recharge. Winter and summer waters contain i) recharge water, or water from the
      variably saturated zone with rapid transfer and high nitrate concentrations, and
      ii) a large contribution (from 35 to 80% in winter and summer, respectively) from
      the lower part of the aquifer (lower weathered aquifer and deep fractured
      aquifer). This induces not only a relatively rapid response of the catchment to
      variations in agricultural pressure, but also a potential inertia which has to be
      taken into account.

PMID- 22854089
TI  - The toxicity of molybdate to freshwater and marine organisms. II. Effects
      assessment of molybdate in the aquatic environment under REACH.
AB  - The REACH Molybdenum Consortium initiated an extensive research program in order
      to generate robust PNECs, based on the SSD approach, for both the freshwater and
      marine environments. This activity was part of the REACH dossier preparation and
      to form the basis for scientific dialogues with other national and international
      regulatory authorities. Chronic ecotoxicity data sets for the freshwater and
      marine environments served as starting point for the derivation of PNECs for both
      compartments, in accordance with the recommended derivation procedures
      established by the European Chemicals Agency (ECHA). The HC(5,50%)s that were
      derived from the generated Species Sensitivity Distributions were 38.2 mg Mo/L
      and 5.75 mg Mo/L for the freshwater and marine water compartment, respectively.
      Uncertainty analysis on both data sets and available data on bioaccumulation at
      high exposure levels justified an assessment factor of 3 on both HC(5,50%)
      leading to a PNEC(freshwater) of 12.7 mg Mo/L and a PNEC(marine) of 1.92 mg Mo/L.
      As there are currently insufficient ecotoxicological data available for the
      derivation of PNECs in the sediment compartment, the equilibrium partitioning
      method was applied; typical K(D)-values for both the freshwater and marine
      compartments were identified and combined with the respective PNEC, leading to a
      PNEC(sediment) of 22,600 mg/kg dry weight and 1980 mg/kg dry weight for
      freshwater and marine sediments, respectively. The chronic data sets were also
      used for the derivation of final chronic values using the procedures that are
      outlined by the US Environmental Protection Agency for deriving such water
      benchmarks. Comparing PNECs with FCVs showed that both methodologies result in
      comparable protective concentration levels for molybdenum in the environment.

PMID- 22854090
TI  - 36 year trends in dissolved organic carbon export from Finnish rivers to the
      Baltic Sea.
AB  - Increasing dissolved organic carbon (DOC) concentrations in lakes, rivers and
      streams in northern mid latitudes have been widely reported during the last two
      decades, but relatively few studies have dealt with trends in DOC export. We
      studied the export of DOC from Finnish rivers to the Baltic Sea between 1975 and
      2010, and estimated trends in DOC fluxes (both flow normalised and non
      normalised). The study encompassed the whole Finnish Baltic Sea catchment area
      (301,000 km(2)) covering major land use patterns in the boreal zone. Finnish
      rivers exported annually over 900,000 t DOC to the Baltic Sea, and the mean area
      specific export was 3.5 t km(-2). The highest export (7.3t km(-2)) was measured
      in peat dominated catchments, whereas catchments rich in lakes had the lowest
      export (2.2 t km(-2)). Inter-annual variation in DOC export was high and
      controlled mainly by hydrology. There was no overall trend in the annual water
      flow, although winter flow increased in northern Finland over 36 years. Despite
      the numerous studies showing increases in DOC concentrations in streams and
      rivers in the northern hemisphere, we could not find any evidence of increases in
      DOC export to the northern Baltic Sea from Finnish catchments since 1975.

PMID- 22854091
TI  - Impact of land-take on the land resource base for crop production in the European
      Union.
AB  - Spatial analyses of cropland productivity levels and land use data from 2000 and
      2006 were performed to assess the loss of cropland resources for biomass
      production of the European Union due to land take. Productivity loss in
      administrative regions was calculated on the basis of the extent and quality of
      agricultural land resources converted to artificial surfaces. Data show that
      while all EU member states experience constant decrease of their production
      capacity, there are also considerable differences among countries and regions.
      Based on the analysis of 24 member states, the EU lost 0.27% of its cropland and
      0.26% of its crop productive potential in the period between 2000 and 2006 due to
      land take. The loss of agricultural land during the study period was the highest
      in the Netherlands, which lost 1.57% of its crop production potential within six
      years. The figures are quite alarming for Cyprus (0.84%), Ireland (0.77%) and
      Spain (0.49%) as well. In metropolitan areas of Barcelona, Berlin, Bratislava,
      Bucharest, Copenhagen, Hamburg, Milan, and Vienna infrastructural investment
      occurred on the higher quality cropland while Budapest, Paris, and Warsaw spread
      their urban growth to areas of less productive cropland. Denmark had to face the
      largest loss of its food production capacity for each citizen, exceeding the
      equivalent of 4 kg capita(-1)year(-1) of wheat, followed by Ireland with more
      than the equivalent of 3 kg wheat and Spain, Netherlands, Hungary, Cyprus and
      France all above 2 kg loss per capita, annually. The EU lost an amount of
      cropland production potential equal to approximately 700,000t of wheat grain,
      annually, in the study period. Results highlight the following general trends:
      (i) land conversion from different land cover types to artificial surfaces
      follows the historic trends in Europe with continuing consumption of more
      productive areas from its land resources; (ii) the conversion rate of croplands
      to artificial surfaces is growing with increased population growth; (iii) with
      the growing rate of population increase, increasingly higher quality croplands
      are converted to artificial surfaces, while with faster rates of population
      decline increasingly poorer quality croplands are converted; (iv) countries with
      more developed economies generally convert cropland at a higher speed; and (v)
      there is a negative correlation between annual economic growth and the rate of
      cropland conversion.

PMID- 22854092
TI  - Temperature modifies the acute effect of particulate air pollution on mortality
      in eight Chinese cities.
AB  - BACKGROUND: Both temperature and particulate air pollution are associated with
      increased death risk. However, whether the effect of particulate air pollution on
      mortality is modified by temperature remains unsettled. METHODS: A stratified
      time-series analysis was conducted to examine whether the effects of particulate
      matter less than 10 MUm in aerodynamic diameter (PM(10)) on mortality was
      modified by temperature in eight Chinese cities. Poisson regression models
      incorporating natural spline smoothing functions were used to adjust for long
      term and seasonal trends of mortality, as well as other time-varying covariates.
      The bivariate response surface model was applied to visually examine the
      potential interacting effect. The associations between PM(10) and mortality were
      stratified by temperature to examine effect modification. RESULTS: The averaged
      daily concentrations of PM(10) in the eight Chinese cities ranged from 65
      MUg/m(3) to 124 MUg/m(3), which were much higher than in Western countries. We
      found evidence that the effects of PM(10) on mortality may depend on temperature.
      The eight-city combined analysis showed that on "normal" (5th-95th percentile)
      temperature days, a 10-MUg/m(3) increment in PM(10) corresponded to a 0.54% (95%
      CI, 0.39 to 0.69) increase of total mortality, 0.56% (95% CI, 0.36 to 0.76)
      increase of cardiovascular mortality, and 0.80% (95% CI, 0.64 to 0.96) increase
      of respiratory mortality. On high temperature (>95th percentile) days, the
      estimates increased to 1.35% (95% CI, 0.80 to 1.91) for total mortality, 1.57%
      (95% CI, 0.69 to 2.46) for cardiovascular mortality, and 1.79% (95% CI, 0.75 to
      2.83) for respiratory mortality. We did not observe significant effect
      modification by extreme low temperature. CONCLUSIONS: Extreme high temperature
      increased the associations of PM(10) with daily mortality. These findings may
      have implication for the health impact associated with both air pollution and
      global climate change.

PMID- 22854093
TI  - Effect of pH on the adsorption of carbendazim in Polish mineral soils.
AB  - The study aimed to determine the influence of pH on the adsorption of carbendazim
      in soil profiles of three mineral agricultural soils: Hyperdystric Arenosol,
      Haplic Luvisol and Hypereutric Cambisol. In the examined pH range between 3 and 7
      the adsorption of carbendazim was inversely correlated to the pH of the soil. The
      adsorption coefficients were in the range between 0.3 and 151.8 m Lg(-1).
      Decreasing the pH in the soil suspensions from 7 to 3 increased the value of this
      coefficient by 3 to 70 times. A decrease in the amounts of organic matter down
      the soil profiles was not associated with weaker carbendazim adsorption. In the
      samples from all soil horizons, at pH values between 3 and 6, the predominant
      sorption process was carbendazim adsorption on clay minerals. The adsorption of
      carbendazim on organic matter prevailed over that on clays only at pH>6 and only
      in the Ap horizon of the examined soils. The developed mathematical models
      yielded very good results when the adsorption of the protonated form of
      carbendazim was assumed to be the predominant adsorption process on clays
      together with the adsorption of neutral molecules on organic matter and clays.
      The results from both the model fitting and the experiments revealed the negative
      effect of Al oxides and hydroxides and Al cations on the adsorption of the
      protonated form of carbendazim on clay minerals. The developed models
      successfully described the pH-dependent adsorption processes of carbendazim for
      both data from particular soil horizons and those from all three examined soil
      profiles.

PMID- 22854094
TI  - LCA data quality: sensitivity and uncertainty analysis.
AB  - Life cycle assessment (LCA) data quality issues were investigated by using case
      studies on products from starch-polyvinyl alcohol based biopolymers and
      petrochemical alternatives. The time horizon chosen for the characterization
      models was shown to be an important sensitive parameter for the environmental
      profiles of all the polymers. In the global warming potential and the toxicity
      potential categories the comparison between biopolymers and petrochemical
      counterparts altered as the time horizon extended from 20 years to infinite time.
      These case studies demonstrated that the use of a single time horizon provide
      only one perspective on the LCA outcomes which could introduce an inadvertent
      bias into LCA outcomes especially in toxicity impact categories and thus dynamic
      LCA characterization models with varying time horizons are recommended as a
      measure of the robustness for LCAs especially comparative assessments. This study
      also presents an approach to integrate statistical methods into LCA models for
      analyzing uncertainty in industrial and computer-simulated datasets. We
      calibrated probabilities for the LCA outcomes for biopolymer products arising
      from uncertainty in the inventory and from data variation characteristics this
      has enabled assigning confidence to the LCIA outcomes in specific impact
      categories for the biopolymer vs. petrochemical polymer comparisons undertaken.
      Uncertainty combined with the sensitivity analysis carried out in this study has
      led to a transparent increase in confidence in the LCA findings. We conclude that
      LCAs lacking explicit interpretation of the degree of uncertainty and
      sensitivities are of limited value as robust evidence for decision making or
      comparative assertions.

PMID- 22854096
TI  - The effect of prolonged duration of untreated depression on antidepressant
      treatment outcome.
AB  - BACKGROUND: The duration of untreated illness has been considered a likely
      predictor of the course of psychotic disorders. However, there is only sparse
      data concerning the influence of treatment delay on the outcome of mood
      disorders. The present study aimed to assess the effect of prolonged untreated
      depression on the outcome of antidepressant treatment. METHOD: Patients aged 18
      70 years with recent onset of the first lifetime depressive episode were
      systematically recruited by the Danish Psychiatric Central Research Register
      during a 2-year period. A total number of 399 individuals out of 1006 potential
      participants in the Register were interviewed, and 270 fulfilled the inclusion
      criteria. The validity of the diagnosis, duration of untreated illness, remission
      on first-line antidepressant treatment and a number of covariates, including
      psychiatric co-morbidity, personality disorders and traits, stressful life events
      prior to onset, and family history of psychiatric illness, were assessed by
      structured interviews. RESULTS: The remission rate was significantly decreased
      among patients with six months or more of untreated depression as compared to
      patients who were treated with antidepressant medication earlier after onset
      (21.1% versus 33.7%, OR=0.5, 95% CI 0.3 to 0.9, p=0.03). The negative influence
      of a prolonged DUI on the outcome did not seem confounded by any of a wide range
      of demographic and clinical variables. LIMITATIONS: The outcome was evaluated
      retrospectively. The findings cannot be generalized to patients outside hospital
      settings. CONCLUSION: Initiation of antidepressant treatment more than six months
      after onset of first episode depression reduces the chance of obtaining
      remission. The results emphasize the importance of early recognition and
      treatment of patients suffering from depression.

PMID- 22854097
TI  - Gender differences in completed suicides in Istanbul, Turkey.
AB  - BACKGROUND: Psychological autopsy studies have been widely used to identify the
      cause of suicide. However, gender is one of the most frequently replicated
      predictors for suicide. To identify further the significant risk factors for
      suicide among males and females separately. METHOD: Data were obtained from The
      Turkish-Istanbul Forensic Medicine Institute Morgue Department for all suicides
      deaths from April to August 2002 in Istanbul. 124 completed suicides were
      included in the study. RESULTS: This study findings suggest that unemployed, not
      married or in a de facto relationship, previous suicide attempt, and alcohol or
      substance abuse were common amongst those who died by suicide. Most of the
      victims were male; the most frequent suicide methods were hanging and jumping
      down a high building followed by firearms. Both males and females were most
      frequently affected by psychiatric disorders. It was found that 108 cases that
      did not receive psychiatric care attempted suicide for the first time and
      committed suicide. CONCLUSION: This finding suggests that suicides should be
      investigated by an expert team and not by the police and victims' relatives only
      to determine whether they are really suicides or not.

PMID- 22854095
TI  - Self-assessment and characteristics of mixed depression in the French national
      EPIDEP study.
AB  - BACKGROUND: Studies on mixed depression have been conducted so far on the basis
      of DSM-IV manic symptoms, i.e., a list of 7 symptoms which may provide limited
      information on the subsyndromal features associated with a full depressive
      episode. METHODS: As part of the EPIDEP National Multisite French Study of 493
      consecutive DSM-IV major depressive patients evaluated in at least two semi
      structured interviews 1 month apart, 102 (23.8%) were classified as mixed
      depressives (>=3 hypomanic symptoms), and 146 (34%) as pure depressives (0
      hypomanic symptom), after exclusion of bipolar I patients; hypomanic symptoms
      were assessed with the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26
      items) of Ahearn-Carroll in a self assessment format. A narrower definition of
      mixed depression, resting on those MVAS-BP items referring to DSM-IV hypomanic
      symptoms was also tested, as a sensitivity analysis. RESULTS: Compared to pure
      depressives, mixed depressive patients had more psychotic symptoms, atypical
      features and suicide attempts during their index episode; their illness course
      was characterized by early age at onset, frequent episodes, rapid cycling, and
      comorbidities. Mixed depressive patients were more frequently bipolar with a
      family history of bipolar disorder, alcohol abuse, and suicide. A dose-response
      relationship was found between intradepression hypomania and several clinical
      features, including temperament measures. The following independent variables
      were associated with mixed depression: hyperthymic temperament, cyclothymic
      temperament, irritable temperament, and alcohol abuse. Using the narrower
      definition of mixed depression missed risk factors such as suicidality and
      comorbidities. LIMITATIONS: The following are the limitations of this study:
      retrospective design, recall bias, lack of sample homogeneity, no cross
      validation of findings by hetero-evaluation of hypomanic symptoms. CONCLUSIONS:
      EPIDEP data showed the feasibility and face validity of self-assessment of
      intradepressive hypomania. They replicated previous findings on the severity and
      high suicidal risk of mixed depression profile. They confirmed, for mixed
      depression, that mixed states occur when mood episodes are superimposed upon
      temperaments of opposite polarity. They finally suggested that a definition of
      mixed depression only based on DSM-IV-TR hypomanic symptoms may not allow to
      identify the most unstable subforms of the entity.

PMID- 22854098
TI  - Interventions for treating depression in Muslim Patients: a systematic review.
AB  - BACKGROUND: Religious belief is an important determinant of mental health,
      depression is the mental illness responsible for the largest disease burden
      globally, and Islam is the fastest growing world religion. Here we systematically
      review the literature on the engagement of Muslim patients in the treatment of
      depression. METHOD: A search of electronic databases, including non-traditional
      sources, was conducted and content experts were contacted in order to identify
      qualitative studies, quantitative studies and opinion pieces. A standardised data
      extraction pro forma and thematic analysis were applied to included studies.
      RESULTS: 25 studies met the inclusion criteria. Muslims hold many beliefs about
      depression relevant to its treatment. Advice about how to identify and respond to
      such beliefs was contradictory and rarely based upon research evidence. The
      literature is generally of poor quality and rarely distinguishes between religion
      and culture. LIMITATIONS: Many studies do not distinguish between beliefs and
      values that are religious and those that are cultural. The majority of papers
      identified are English language, suggesting that literature from predominantly
      Muslim countries is underrepresented, despite our strategy of searching for
      literature from all relevant countries. CONCLUSION: Much of the evidence
      identified by this review is methodologically weak or includes assertions made
      without qualification. This evidence provides important perspectives, but should
      be interpreted with caution. High-quality research is needed to improve our
      understanding of the treatment of depression in Muslim clients, to determine how
      existing therapies can be modified to meet the needs of Muslim clients, and to
      evaluate the effectiveness of such modified therapies.

PMID- 22854099
TI  - Bipolar depressed patients show both failure to activate and failure to de
      activate during performance of a working memory task.
AB  - BACKGROUND: Bipolar depression has been found to be associated with changes in
      prefrontal cortex activity during performance of cognitive tasks. However, the
      role of task-related de-activations has been little investigated. METHOD: Forty
      one bipolar depressed patients and 41 matched normal controls underwent fMRI
      scanning while performing baseline, 1-back and 2-back versions of the n-back
      task. Linear models were used to obtain maps of within-group activations and
      areas of differential activation between the groups. RESULTS: The bipolar
      depressed patients showed reduced activation in the dorsolateral prefrontal
      cortex (DLPFC) bilaterally and several other regions. After controlling for
      differences in task performance only differences in the DLPFC and cerebellum
      remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS
      scores. The patients showed failure to de-activate in the medial prefrontal
      cortex, an area corresponding to the anterior medial node of the default mode
      network. LIMITATIONS: To confirm default mode network dysfunction demonstration
      of resting-state connectivity abnormalities would also be required. The study was
      carried out on treated patients, and did not assess for presence of depressive
      symptoms in the healthy controls. CONCLUSIONS: Both prefrontal cortical and
      default mode network dysfunction appear to characterise bipolar depression. The
      former, but not the latter, is associated with symptom severity.

PMID- 22854100
TI  - Interrelationship of depression, stress and inflammation in cancer patients: a
      preliminary study.
AB  - OBJECTIVE: Depression is common in cancer patients and detrimentally affects
      patients' quality of life. Both depression and stress are associated with raised
      inflammatory marker levels. This prospective study of cancer patients focuses on
      childhood trauma, recent life events and inflammatory marker levels as risk
      factors for high post-surgery depressive symptoms. METHODS: Ninety cancer
      patients (56 head and neck, 34 colorectal) completed the Hospital Anxiety and
      Depression Scale, pre-surgery and six, 12 and 24 weeks post-surgery. Recent life
      events and childhood trauma were assessed at six and 12 weeks respectively. Blood
      samples were taken pre- and one and six weeks post-surgery to measure C-reactive
      protein (CRP) and pro-inflammatory cytokine levels. RESULTS: Childhood trauma and
      recent life events were risk factors for higher depressive symptom levels. In
      colorectal cancer patients, baseline CRP levels were associated with depressive
      symptom levels at six (p=0.008) and 12 weeks (p=0.038). Baseline and six week
      Tumour Necrosis Factor-alpha (TNFalpha) levels were significantly associated with
      higher depressive symptoms at later time points after adjusting for cancer
      related variables. Childhood trauma was positively associated with TNFalpha and
      CRP levels in colorectal cancer patients. The associations between inflammatory
      markers and depressive symptoms were not significant after adjusting for
      childhood trauma. LIMITATIONS: Small sample size. CONCLUSIONS: Raised
      inflammatory mediator levels may be risk factors for depressive symptoms in
      colorectal cancer patients and thus worth considering as a potential therapeutic
      target. These pilot data support recent findings demonstrating long-term effects
      of childhood adversity on adult health.

PMID- 22854102
TI  - A neural-based code for computing image velocity from small sets of middle
      temporal (MT/V5) neuron inputs.
AB  - It is still not known how the primate visual system is able to measure the
      velocity of moving stimuli such as edges and dots. Neurons have been found in the
      Medial Superior Temporal (MST) area of the primate brain that respond at a rate
      proportional to the speed of the stimulus but it is not clear how this property
      is derived from the speed-tuned Middle Temporal (MT) neurons that precede area
      MST along the visual motion pathway. I show that a population code based on the
      outputs from a number of MT neurons is susceptible to errors if the MT neurons
      are tuned to a broad range of spatial frequencies and have receptive fields that
      span a wide range of sizes. I present a solution that uses the activity of just
      three MT units within a velocity channel to estimate the velocity using a
      weighted vector average (centroid) technique. I use a range of velocity channels
      (1, 2, 4, and 8 degrees /s) with inhibition between them so that only a single
      channel passes the velocity estimate onto the next stage of processing (MST). I
      also include a contrast-dependent redundancy-removal stage which provides tighter
      spatial resolution for the velocity estimates under conditions of high contrast
      but which trades off spatial compactness for greater sensitivity at low contrast.
      The new model produces an output signal proportional to the stimulus input
      velocity (consistent with MST neurons) and its input stages have properties
      closely tied to those of neurons in areas V1 and MT.

PMID- 22854101
TI  - Analysis of sex differences in preadmission management of ST-segment elevation
      (STEMI) myocardial infarction.
AB  - BACKGROUND: Many reports suggest gender disparity in cardiac care as a
      contributor to the increased mortality among women with heart disease. OBJECTIVE:
      We sought to identify gender differences in the management of Myocardial
      Infarction (MI) Alert-activated ST-segment elevation myocardial infarction
      (STEMI) patients that may have resulted from prehospital initiation. METHODS: A
      retrospective database was created for MI Alert STEMI patients who presented to
      the emergency department (ED) of an academic community hospital with 74,000
      annual visits from April 2000 through December 2008. Included were patients
      meeting criteria for an MI Alert (an institutional clinical practice guideline
      designed to expedite cardiac catheterization for STEMI patients). Data points
      (before and after initiation of a prehospital alert protocol) were compared and
      used as markers of therapy: time to ECG, receiving beta-blockers, and time to the
      catheterization laboratory (cath lab). Differences in categorical variables by
      patient sex were assessed using the chi(2) test. Medians were estimated as the
      measure of central tendency. Quantile regression models were used to assess
      differences in median times between subgroups. RESULTS: A total of 1231 MI Alert
      charts were identified and analyzed. The majority of the study population were
      male (70%), arrived at the ED via ambulance (60.1%), and were taking a beta
      blocker (67.8%) or aspirin (91.6%) at the time of the ED admission. Female
      patients were more likely than male patients to arrive at the ED via ambulance
      (65.9% vs 57.6%, respectively; P = 0.014). The median age of female patients was
      68 years, whereas male patients were significantly younger (median age, 59 years;
      P < 0.001). The proportion of patients currently taking a beta-blocker or low
      dose aspirin did not vary by gender. Overall, 78.2% of the MI Alert patients
      arriving at the ED were MI2 (alert initiated by ED physician), and this did not
      vary by gender (P = 0.33). A total of 1064 MI Alert patients went to the cath
      lab: 766 male patients (88.9%) and 298 female patients (80.8%). Overall, the
      median time to cath lab arrival was 79 minutes for men and 81 minutes for women
      (P = 0.38). Overall, the median time to cath lab arrival significantly decreased
      from MI1 to MI3, (P(trend) < 0.001). For prehospital-initiated alerts (MI3), the
      median time to cath lab arrival was the same for men and women (64 minutes; P =
      1.0). For hospital-initiated alerts, time to cath lab arrival was 82 minutes for
      male patients and 84 minutes for female patients (P = 0.38). Prehospital
      activation of the process decreased the time to the cath lab by 19 minutes (P <
      0.001; 95% CI, 13.2-24.8). CONCLUSION: No significant gender differences were
      apparent in the STEMI patients analyzed, whether the MI Alert was initiated in
      the ED or prehospital initiated. Initiating prehospital-based alerts
      significantly decreased the time to the cath lab.

PMID- 22854103
TI  - Climate change and coupling of macronutrient cycles along the atmospheric,
      terrestrial, freshwater and estuarine continuum.
AB  - This paper provides an introduction to the Special Issue on "Climate Change and
      Coupling of Macronutrient Cycles along the Atmospheric, Terrestrial, Freshwater
      and Estuarine Continuum", dedicated to Colin Neal on his retirement. It is not
      intended to be a review of this vast subject, but an attempt to synthesize some
      of the major findings from the 22 contributions to the Special Issue in the
      context of what is already known. The major research challenges involved in
      understanding coupled macronutrient cycles in these environmental media are
      highlighted, and the difficulties of making credible predictions of the effects
      of climate change are discussed. Of particular concern is the possibility of
      interactions which will enhance greenhouse gas concentrations and provide
      positive feedback to global warming.

PMID- 22854105
TI  - Acute severe encephalopathy related to human herpesvirus-6 infection in a patient
      with carnitine palmitoyltransferase 2 deficiency carrying thermolabile variants.
AB  - We describe a male infant with carnitine palmitoyltransferase 2 (CPT2) deficiency
      who presented with acute encephalopathy related to human herpesvirus-6 (HHV-6)
      infection. He was hospitalized for pylexia and status epilepticus, diagnosed with
      acute encephalopathy, and treated with intensive supportive care including
      mechanical ventilation, support for hypothermia, and control of the intracranial
      pressure, that caused severe neurological sequelae. HHV-6 was detected in his
      cerebrospinal fluid, indicating HHV-6 related encephalopathy. In the acute phase,
      acylcarnitine analysis of blood suggested a defect of long chain fatty acid beta
      oxidation, and CPT2 deficiency was genetically confirmed. In addition, other gene
      alterations that have been previously reported as "thermolabile variants" were
      found. Some patients with the infantile form of CPT2 deficiency present with
      acute encephalopathy, but others do not develop encephalopathy. The correlation
      between phenotype and genotype has not been clarified. Our case may contribute to
      the elucidation of the genetic factor involved in acute encephalopathy in CPT2
      deficiency.

PMID- 22854104
TI  - Intrinsic unresponsiveness of Mertk-/- B cells to chronic graft-versus-host
      disease is associated with unmodulated CD1d expression.
AB  - Activation and migration of marginal zone B (MZB) cells into follicular (FO)
      regions of the spleen has been proposed as one of the mechanisms that regulate
      the development of autoreactive B cells. The mer receptor tyrosine kinase (Mertk)
      mediates apoptotic cell clearance and regulates activation and cytokine
      secretion. In the well-studied class II chronic GVH model of bm12 cells into B6
      hosts, we observed that Mertk deficient B6 mice did not generate autoantibodies
      in response to this allogeneic stimulus. We posited that Mertk is important in
      MHC-II-mediated B cell signaling. In the present study, we show that B cells from
      Mertk(-/-) mice but not WT B6 mice exhibited decreased calcium mobilization and
      tyrosine phosphorylation when stimulated by MHC-II cross-linking. The finding
      that Mertk was important for class II signaling in B cells was further supported
      by the preponderance of a-allotype autoantibodies in cGVH in RAG-KO mice
      reconstituted with a mixture of bone marrow from Mertk(-/-) mice (b-allotype) and
      C20 mice (a-allotype). MZB cells from Mertk(-/-) mice were unable to down
      regulate surface CD1d expression and subsequent inclusion in the MZ, associated
      with significantly lower germinal center responses compared to MZB cells from WT.
      Moreover, Mertk(-/-) mice treated with an anti-CD1d down regulating antibody
      responded significantly to bm12 cells, while no response was observed in Mertk(-/
      ) mice treated with control antibodies. Taken together, these findings extend the
      role of Mertk to include CD1d down regulation on MZB cells, a potential mechanism
      limiting B cell activation in cGVH.

PMID- 22854106
TI  - Food addiction and body-mass-index: a non-linear relationship.
AB  - Excessive food consumption has been recognized to show similarities with
      substance dependence. Subsequently, it has been proposed that food addiction
      might contribute to the obesity epidemic. Recent studies using questionnaires for
      the assessment of food addiction have found statistically significant, but
      negligible positive correlations with body-mass-index (BMI). Moreover, group
      comparisons between food-addicted and non-addicted individuals in normal-weight
      or obese samples did not show differences in BMI. However, the prevalence of food
      addiction diagnoses is remarkably increased in obese individuals. In the current
      article, it is suggested that there might be a cubic relationship between food
      addiction and BMI. Food addiction symptomatology may remain stable in the under-
      and normal-weight range, increase in the overweight- and obese range, and level
      off at severe obesity. Empirical data in support of this view are presented.

PMID- 22854107
TI  - Imaging of the beta-cells of the islets of Langerhans.
AB  - The major aim of this paper is to review the present status of the techniques for
      the non-invasive imaging and quantification of insulin-producing pancreatic islet
      beta-cells. Emphasis is placed on both the expansion of prior work already
      considered in a prior review and novel achievements. Thus, the use of d
      mannoheptulose analogs, hypoglycemic sulfonylureas and glinides, neural imaging
      agents, neuro-hormonal receptor ligands and nanoparticles is first dealt with.
      Thereafter, consideration is given on optical imaging technologies, the
      identification of new beta-cells specific binding and target proteins, the
      functional imaging of islets transplanted into the eye anterior chamber and in
      vivo manganese-enhanced magnetic resonance imaging.

PMID- 22854108
TI  - An extra-large ovarian mucinous cystadenoma in a premenarchal girl and a review
      of the literature.
AB  - OBJECTIVE: Epithelial ovarian neoplasms are extremely uncommon in children.
      Ovarian mucinous cystadenoma is benign and an extremely rare presentation in the
      premenarchal period. We present a case of giant mucinous cystadenoma of the left
      ovary in a 13-year-old and a review of the supporting literature. CASE REPORT:
      The patient was admitted with a history of increasing abdominal distension and
      pain for approximately 3 months and a history of an ovarian mass for 3 years. An
      adnexal mass measuring 40 * 30 * 20 cm was detected by abdominal ultrasonography
      and computed tomography. The tumor markers CEA, CA 19-9, and CA-125 were
      elevated, although alpha-fetoprotein and human chorionic antigen levels were
      within the normal range. The patient underwent surgery. The smooth-surfaced mass
      filled the abdomen. A frozen section biopsy was performed, and the results
      indicated a benign mucinous cystadenoma. A unilateral oophorectomy with tumor
      removal was performed. CONCLUSION: The ovarian mass was revealed by abdominal
      distension, and a diagnosis was established by frozen biopsy. Complete and
      careful surgical resection provides satisfactory results; however, careful follow
      up is required.

PMID- 22854109
TI  - High-fat, high-fructose diet induces hepatic iron overload via a hepcidin
      independent mechanism prior to the onset of liver steatosis and insulin
      resistance in mice.
AB  - OBJECTIVE: Excess iron deposition in tissues leads to increased oxidative stress.
      The clinical observation that non-alcoholic fatty liver disease (NAFLD) is
      frequently associated with hepatic iron overload (HIO) indicates that iron
      induced oxidative stress may be related to NAFLD pathology. Decreased expression
      of hepcidin, a hepatic hormone that suppresses dietary iron absorption in the
      duodenum, is frequently observed in NAFLD patients and has been postulated to be
      a cause of HIO. MATERIALS/METHODS: Because dietary fat and fructose intake play
      roles in the onset of NAFLD, we fed C57BL/6J mice a high-fat, high-fructose
      (HFHFr) diet for 16 weeks to study the relationship between hepatic iron content
      and NAFLD. RESULTS: Within 4 weeks after the start of the experiment, the mice
      exhibited significant increases in hepatic free fatty acid (FFA) content, serum
      insulin levels, and the homeostasis model assessment of insulin resistance.
      Interestingly, hepatic iron content and oxidative stress significantly increased
      with the HFHFr diet 2 weeks earlier than hepatic FFA accumulation and decreased
      insulin sensitivity. Moreover, hepatic hepcidin expression was significantly
      downregulated, as is also observed in NAFLD patients, but much later than the
      onset of HIO. CONCLUSIONS: Accordingly, our data demonstrated that HIO may have a
      pathogenic role in the onset of liver steatosis and insulin resistance. Moreover,
      distinct mechanisms, in addition to hepcidin, may underlie NAFLD-related HIO.
      These data suggest that the HFHFr diet can be used for establishing a suitable
      model to study the precise mechanism of HIO in NAFLD patients.

PMID- 22854110
TI  - Monopolar electrocautery versus ultrasonic dissection of the gallbladder from the
      gallbladder bed in laparoscopic cholecystectomy: a randomized controlled trial.
AB  - BACKGROUND: Ultrasonic dissection has been suggested as an alternative to
      monopolar electrocautery in laparoscopic cholecystectomy because it generates
      less tissue damage and may have a lower incidence of gallbladder perforation. We
      compared the 2 methods to determine the incidence of gallbladder perforation and
      its intraoperative consequences. METHODS: We conducted a prospective randomized
      controlled trial between July 2008 and December 2009 involving adult patients
      with symptomatic gall stone disease who were eligible for laparoscopic
      cholecystectomy. Patients were randomly assigned before administration of
      anesthesia to electrocautery or ultrasonic dissection. Both groups were compared
      for incidence of gallbladder perforation during dissection, bile leak, stones
      spillage, lens cleaning, duration of surgery and estimation of risk of
      gallbladder in the presence of complicating factors. RESULTS: We included 60
      adult patients in our study. The groups were comparable with respect to
      demographic characteristics, symptomatology, comorbidities, previous abdominal
      surgeries, preoperative ultrasonography findings and intraoperative
      complications. The overall incidence of gallbladder perforation was 28.3% (40.0%
      in the electrocautery v. 16.7% in the ultrasonic dissection group, p = 0.045).
      Bile leak occurred in 40.0% of patients in the electrocautery group and 16.7% of
      patients in ultrasonic group (p = 0.045). Lens cleaning time (p = 0.015) and
      duration of surgery (p = 0.001) were longer in the electrocautery than the
      ultrasonic dissection group. There was no statistical difference in stone
      spillage between the groups (p = 0.62). CONCLUSION: Ultrasonic dissection is safe
      and effective, and it improves the operative course of laparoscopic
      cholecystectomy by reducing the incidence of gallbladder perforation.

PMID- 22854111
TI  - Attending surgeon burnout and satisfaction with the establishment of a regional
      acute care surgical service.
AB  - BACKGROUND: Establishment of the Acute Care Surgical Service (ACSS) has
      dramatically changed the management of acute, nontrauma surgical patients in
      Winnipeg, Manitoba. Its formation was partially driven by increasing strain on
      surgeons and surgical services. We sought to determine surgeon level of burnout
      and satisfaction with the ACSS. METHODS: All Winnipeg ACSS surgeons were mailed
      surveys. Burnout was established using the Maslach Burnout Inventory Human
      Services Survey. Satisfaction was ascertained with a series of questions.
      RESULTS: We attained a response rate of 76%. Most surgeons were married men with
      children. A burnout level of 61% was determined. Although most surgeons felt the
      ACSS was a positive change in their careers, they felt that operating room
      accessibility and teaching opportunities were lacking. CONCLUSION: Although a
      high level of burnout exists among ACSS surgeons, most are satisfied with its
      establishment. Factors such as operating room accessibility and teaching
      opportunities must be addressed.

PMID- 22854112
TI  - Comparison of lateral thermal damage of the human peritoneum using monopolar
      diathermy, Harmonic scalpel and LigaSure.
AB  - BACKGROUND: New hemostatic technologies are often employed in open and
      laparoscopic surgery to reduce duration of surgery and complications. Monopolar
      diathermy, Harmonic scalpel and LigaSure are routinely used in open and
      laparoscopic surgery for tissue cutting and hemostasis. We compared lateral
      thermal damage following in vivo application of 3 commonly used instruments.
      METHODS: We used monopolar diathermy, Harmonic scalpel and LigaSure to coagulate
      and divide the peritoneum of patients who underwent median laparotomy. After
      anesthesia, median supraumbilical laparotomy was performed, and the peritoneum of
      each patient was coagulated using different devices. Using light microscopy and
      morphometric imaging analysis, the width of tissue lateral thermal damage was
      measured from the point of the peritoneal incision. RESULTS: We included 100
      patients in our study. After a peritoneal incision, the mean lateral thermal
      damage of monopolar diathermy, Harmonic scalpel (output power 3), Harmonic
      scalpel (output power 5) and LigaSure were 215.79 MUm, 90.42 MUm, 127.48 MUm and
      144.18 MUm, respectively. CONCLUSION: The degree of lateral thermal spread varied
      by instrument type, power setting and application time. LigaSure and Harmonic
      scalpel were the safest and most efficient methods of tissue coagulation.
      Monopolar diathermy resulted in the greatest degree of thermal damage in tissues.

PMID- 22854114
TI  - Endoscopic treatment of vesicoureteral reflux in children with subureteral
      dextranomer/hyaluronic acid injection: a single-centre, 7-year experience.
AB  - BACKGROUND: The goals of medical intervention in patients with vesicoureteral
      reflux are to allow normal renal growth, prevent infections and pyelonephritis,
      and prevent renal failure. We present our experience with endoscopic treatment of
      vesicoureteral reflux in children by subureteral dextranomer/hyaluronic acid
      copolymer injection. METHODS: Under cystoscopic guidance, dextranomer/hyaluronic
      acid copolymer underneath the intravesical portion of the ureter in a subureteral
      or submucosal location was injected in patients undergoing endoscopic correction
      of vesicoureteral reflux. RESULTS: A total of 282 patients (120 boys and 162
      girls) underwent the procedure. There were 396 refluxed ureters altogether. The
      mean age of patients was 4.9 years. The mean overall follow-up period was 44
      months. Among the 396 ureters treated, 76% were cured with a single injection. A
      second and third injection raised the cure rate to 93% and 94%, respectively.
      Twenty-two (6%) ureters failed all 3 injections, and were converted to open
      surgery. CONCLUSION: Endoscopic treatment of vesicoureteral reflux can be
      recommended as a first-line therapy for most cases of vesicoureteral reflux,
      because of the short hospital stay, absence of complications and the high success
      rate.

PMID- 22854113
TI  - Managing complications associated with laparoscopic Roux-en-Y gastric bypass for
      morbid obesity.
AB  - Obesity has become a major health concern in Canada. This has resulted in a
      steady rise in the number of bariatric surgical procedures being performed
      nationwide. The laparoscopic Roux-en-Y gastric bypass (LRYGB) is not only the
      most common bariatric procedure, but also the gold standard to which all others
      are compared. With this in mind, it is imperative that all gastrointestinal
      surgeons understand the LRYGB and have a working knowledge of the common
      postoperative complications and their management. Early postoperative
      complications following LRYGB that demand immediate recognition include
      anastomotic or staple line leak, postoperative hemorrhage, bowel obstruction and
      incorrect Roux limb reconstructions. Later complications may be challenging to
      differentiate from other gastrointestinal disorders and include anastomotic
      stricture, marginal ulceration, fistula formation, weight gain and nutritional
      deficiencies. We discuss the principles involved in the management of each
      complication and the timing of referral to specialist bariatric centres.

PMID- 22854116
TI  - Factors associated with needlestick and sharp injuries among hospital nurses: a
      cross-sectional questionnaire survey.
AB  - BACKGROUND: The current status of needlestick or sharp injuries of hospital
      nurses and factors associated with the injuries have not been systematically
      examined with representative registered nurse samples in South Korea. OBJECTIVE:
      To examine the incidence to needlestick or sharp injuries and identify the
      factors associated with such injuries among hospital nurses in South Korea.
      DESIGN, SETTINGS AND PARTICIPANTS: A cross-sectional survey of hospital nurses in
      South Korea. Data were collected from 3079 registered nurses in 60 acute
      hospitals in South Korea by a stratified random sampling method based on the
      region and number of beds. METHODS: The dependent variable was the occurrence of
      needlestick or sharp injuries in the last year, and the independent variables
      were protective equipment, nurse characteristics, and hospital characteristics.
      This study employed logistic regression analysis with generalized estimating
      equation clustering by hospital to identify the factors associated with
      needlestick or sharp injuries. RESULTS: The majority (70.4%) of the hospital
      nurses had experienced needlestick or sharp injuries in the previous year. The
      non-use of safety containers for disposal of sharps and needles, less working
      experience as a registered nurse, poor work environments in regards to staffing
      and resource adequacy, and high emotional exhaustion significantly increased risk
      for needlestick or sharp injuries. Working in perioperative units also
      significantly increased the risk for such injuries but working in intensive care
      units, psychiatry, and obstetrics wards showed a significantly lower risk than
      medical-surgical wards. CONCLUSIONS: The occurrence of needlestick or sharp
      injuries of registered nurses was associated with organizational characteristics
      as well as protective equipment and nurse characteristics. Hospitals can prevent
      or reduce such injuries by establishing better work environments in terms of
      staffing and resource adequacy, minimizing emotional exhaustion, and retaining
      more experienced nurses. All hospitals should make safety-engineered equipment
      available to registered nurses. Hospitals as well as specific units showing
      higher risk for needlestick and sharp injuries should implement organizational
      strategies to prevent such injuries. It is also necessary to establish a
      monitoring system of needlestick and sharp injuries at a hospital level and a
      reporting system at the national level in South Korea.

PMID- 22854117
TI  - Sense of coherence is a predictor of perceived health in adolescents with
      congenital heart disease: a cross-lagged prospective study.
AB  - BACKGROUND: The life expectancy of patients with congenital heart disease (CHD)
      has increased substantially. Health care should meet their needs through
      enhancing psychological functioning, quality of life, and perceived health. A
      possible determinant of these variables is sense of coherence (SOC). The
      interplay between SOC and outcome variables is not thoroughly scrutinized yet.
      OBJECTIVE: To examine the direction of relationships between SOC and domains of
      perceived health in adolescents with CHD. DESIGN: A longitudinal, observational
      study with two measurement points and a time lag of nine months. SETTING: The
      pediatric and congenital cardiology department of a university hospital in
      Belgium. PARTICIPANTS: Adolescents with CHD (n=429 at time 1) were recruited from
      the hospital's database. At time 1, mean age was 15.8 years, 53.4% were boys, and
      most adolescents had a moderately complex heart defect (47.6%). METHODS:
      Participants filled out the 13-item SOC questionnaire and the PedsQL scale at
      both time points. Cross-lagged path analysis using structural equation modeling
      was conducted, controlling for age, sex, educational level, disease complexity,
      and prior heart surgery for CHD. RESULTS: SOC at time 1 positively predicted all
      domains of generic perceived health (physical, emotional, social, and school
      functioning) and three out of five domains of disease-specific perceived health
      (symptoms, physical appearance, and cognitive problems) at time 2. Conversely,
      better school functioning and less cognitive problems at time 1 positively
      predicted SOC at time 2. CONCLUSIONS: Evidence was obtained for reciprocal
      pathways between SOC and the domains of perceived health, although the
      predominant direction of effects was found to be from SOC to perceived health.
      Hence, improving SOC has the potential to enhance future perceived health of
      adolescents with CHD.

PMID- 22854115
TI  - Lynch syndrome in a predominantly Afrocentric population: a clinicopathological
      and genetic study.
AB  - BACKGROUND: We investigated the prevalence of Lynch syndrome as a hereditary
      cause of colon cancer in the young Jamaican colorectal cancer (CRC) population.
      METHODS: We identified patients aged 40 years or younger in whom primary CRC was
      diagnosed at the University Hospital of the West Indies from January 2004 to
      December 2008. We reviewed the medical records and hematoxylin and eosin (H&E)
      stained histopathology slides. Tumour blocks were tested for microsatellite
      instability (MSI). Patients with MSI-high phenotype (MSI-H) tumours had genetic
      counselling, after which genomic DNA was extracted from peripheral blood to test
      for MLH1 and MSH2 germline mutations. Patients also had pedigree mapping.
      RESULTS: There were 25 patients with CRC aged 40 years or younger with no history
      of hereditary colon cancer syndrome. The patients' mean age was 33 (range 21-40)
      years. Histopathologic review confirmed CRC in all patients; 8 of 25 (32%) showed
      morphologic features suggestive of MSI. We detected MSI-H in 5 of 23 (22%) tumour
      blocks tested. Review with H&E staining correctly identified 80% of cases
      positive for MSI-H. The false-positive rate and positive predictive value on H&E
      review was 50%. The negative predictive value of histomorphologic H&E review was
      94%. Three patients were available for and had mutational analysis of DNA
      mismatch repair genes; 2 were positive for mutations in keeping with Lynch
      syndrome and 1 had MLH1 alterations of uncertain significance. All 3 met the
      Amsterdam criteria for hereditary nonpolyposis CRC. CONCLUSION: Thirteen percent
      of the population had mutations in keeping with Lynch syndrome. This prevalence
      is similar to that reported for white populations.

PMID- 22854118
TI  - Neonatal morbidity in growth-discordant monochorionic twins: comparison between
      the larger and the smaller twin.
AB  - Fetal growth restriction in singletons has been shown to enhance fetal lung
      maturation and reduce the risk of respiratory distress syndrome due to increased
      endogenous steroid production. However, data on lung maturation in growth
      discordant monochorionic (thus, identical) twins are lacking. Our objective was
      to compare the risk of severe neonatal morbidity between the larger and the
      smaller twin in monochorionic twins with birth weight discordance (BWD). We
      included in the study all consecutive monochorionic diamniotic pregnancies with
      severe BWD (>=25%) and two live-born twins delivered at our center (n=47 twin
      pairs). We compared the incidence of neonatal morbidity, particularly respiratory
      distress syndrome (RDS), and cerebral lesions between the larger and the smaller
      co-twin. The incidence of severe neonatal morbidity in the larger and smaller
      twin was 38% (18/47) and 19% (9/47), respectively (odds ratio (OR) 2.66, 95%
      confidence interval (CI) 0.94-7.44) and was due primarily to the higher incidence
      of RDS, 32% (15/47) and 6% (3/47), respectively (OR 6.88, 95% CI 1.66-32.83). In
      conclusion, this study shows that the larger twin in monochorionic twin pairs
      with BWD is at increased risk of severe neonatal morbidity, particularly RDS,
      compared to the smaller twin.

PMID- 22854119
TI  - Chronic pain leads to concomitant noradrenergic impairment and mood disorders.
AB  - BACKGROUND: Patients suffering chronic pain are at high risk of suffering long
      lasting emotional disturbances characterized by persistent low mood and anxiety.
      We propose that this might be the result of a functional impairment in
      noradrenergic circuits associated with locus coeruleus (LC) and prefrontal
      cortex, where emotional and sensorial pain processes overlap. METHODS: We used a
      chronic constriction injury of sciatic nerve as a model of neuropathic pain in
      male Sprague-Dawley rats to assess the time-dependent changes that might
      potentially precipitate mood disorders (2, 7, 14, and 28 days after injury). This
      was measured through a combination of behavioral, electrophysiological,
      microdialysis, immunohistochemical, and Western blot assays. RESULTS: As
      expected, nerve injury produced an early and stable decrease in sensorial pain
      threshold over the testing period. By contrast, long-term neuropathic pain (28
      days after injury) resulted in an inability to cope with stressful situations,
      provoking depressive and anxiogenic-like behaviors, even more intense than the
      aversiveness associated with pain perception. The onset of these behavioral
      changes coincided with irruption of noradrenergic dysfunction, evident as: an
      increase in LC bursting activity; in tyrosine hydroxylase expression and that of
      the noradrenaline transporter; and enhanced expression and sensitivity of alpha2
      adrenoceptors in the LC. CONCLUSIONS: Long-term neuropathic pain leads to anxio
      depressive-like behaviors that are more predominant than the aversion of a
      painful experience. These changes are consistent with the impairment of
      noradrenergic system described in depressive disorders.

PMID- 22854120
TI  - Phylogenomic analysis of polyketide synthase genes in actinomycetes: structural
      analysis of KS domains and modules of polyketide synthases.
AB  - Polyketides are complex and diverse secondary metabolites, synthesised by large
      multifunctional enzymes, Polyketide Synthases (PKS). The phylogenomic analysis of
      beta-ketosynthase (KS) domains and PKSs within actinomycetes suggests the
      contribution of point mutations, gene duplications, horizontal gene transfer and
      homologous recombination in the evolution of PKSs. PKS genealogy suggested the
      ancestral module structure with KS-AT-ACP domain composition. KS domains showed
      similar core and highly variable loop regions at the dimer interface, which seems
      to affect the selectivity of the primer unit. In PKS modules, the linker regions
      comprise a significant fraction of the module. The reducing domains
      (ketoreductase and dehydrogenase) protrude out from the central axis of the
      module and also responsible for extreme variability in the final products. Thus,
      phylogenomic and structural analysis of PKSs can assist in the artificial
      reprogramming of PKSs.

PMID- 22854121
TI  - 3D QSAR CoMFA/CoMSIA and docking studies on azole dione derivatives, as anti
      cancer inhibitors.
AB  - Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity
      Indices Analysis (CoMSIA) were performed on a series of 103 azole dione
      derivatives, as selective anti-cancer inhibitors. The atom and shape based root
      mean square alignment yielded the best predictive CoMFA model q2 = 0.923, r2 =
      0.980, when compared with the CoMSIA model. Docking studies were employed to
      position the inhibitors into active site of Crystal Structure of Delta (4)-3
      ketosteroid 5-beta-reductase (PDB id: 3BUR). Results that indicate steric,
      electrostatic, hydrophobic, hydrogen bond donor and acceptor substituents play a
      significant role in design novel, potent and selective anti-cancer activity of
      the compounds.

PMID- 22854122
TI  - Targeting Pim-1 kinase for potential drug-development.
AB  - Dysregulation of Pim-1 kinase has been implicated in several human cancers. Many
      potential inhibitors of PIM kinase have been reported, but potential bioactive
      compounds are still far from reach. Keeping this in mind, we have selected
      structurally known diverse Pim-1 kinase inhibitors to find novel small molecule
      drug-leads. A ligand-based pharmacophore model for Pim-1 kinase was developed
      using PHASE software. A four feature pharmacophoric hypothesis (AAHR) was used to
      develop atom-based 3D-QSAR model with the best regression coefficient of 0.9433
      and Pearson-R of 0.9344. Compounds from Asinex platinum database were obtained
      whose pIC(50) values matched the 3D-QSAR model. Structural and molecular
      interaction studies on the training and test sets suggest that designing novel
      compounds hydrogen bond with Asp128 in the bioactive region of Pim-1 kinase would
      result in therapeutic success.

PMID- 22854123
TI  - Development of an integrated network visualisation and graph analysis tool for
      biological networks.
AB  - There has been a steady increase in the amount of molecular data generated by
      experiments and computational methods performed on biological networks. There is
      a growing need to obtain an insight into the organisation and structure of the
      massive and complex biological networks formed by the interacting molecules. To
      that end, this paper presents a newly developed plugin for integrated network
      visualisation and graph analysis within the Cytoscape framework. The plugin is
      capable of computing and visualising a comprehensive set of node and graph level
      statistics. The evaluation of the plugin on a range of biological networks and
      its memory performance is conducted. The plugin, proven to be scalable, is an
      interactive and highly customisable application that expects no prior knowledge
      in graph theory from users.

PMID- 22854124
TI  - Genome wide search for identification of potential drug targets in Bacillus
      anthracis.
AB  - With the heightened interest in Bacillus anthracis as a potential biological
      threat agent, novel drug targets identification is of great importance in drug
      discovery. This study considered a genome-wide approach to identify 270 non
      redundant, non-human homologous genes and 103 essential genes of the bacteria as
      putative drug targets. Sub-cellular localisation of each drug target was
      annotated using PSORTb 3.0 and confirmation by a hybrid support vector machine
      analysis identified 16 membrane-bound genes with reliability index >=4. SPAAN
      analysis predicted 3 adhesion-like proteins and BLAST against the MEROPS database
      identified 7 peptidases with inhibitors. As a case study, a homology model was
      built for the ptsG gene using Modeller 9v8. The work reported here identified a
      small subset of potential drug targets involved in vital aspects of the
      metabolism of pathogen, persistence, virulence and cell wall biosynthesis. Thus,
      this manifold workflow can speed up the process of drug target discovery.

PMID- 22854125
TI  - First identification of Culex flavivirus (Flaviviridae) in Brazil.
AB  - INTRODUCTION: Culex flavivirus (CxFV) was first isolated in 2007 from Culex
      pipiens in Japan and then identified in several other countries. Characterization
      of the CxFV showed that all strains are related to the cell fusing agent virus.
      In this manuscript we report the first identification of CxFV in South America.
      MATERIAL AND METHODS: We have collected Culex sp. mosquitoes using BG-Sentinel
      traps and manual aspirators. They were pooled according to genus, species, sex
      and location. Viral RNA was extracted and multiplex nested PCR was performed to
      test the presence of Flavivirus. The positive samples were isolated in C6/36
      cells and sequenced for phylogenetic analyses. RESULTS: 265 female Culex
      mosquitoes pooled in 83 pools were tested with specific CxFV, Saint Louis
      encephalitis virus (SLEV) and West Nile virus (WNV) primers. Our sequence data
      indicated maximum sequence similarity of 97% with CxFV. DISCUSSION: In this study
      we report the circulation of CxFV in an urban setting where SLEV had previously
      caused an outbreak. In terms of public health, this is an important finding due
      to the assumption that the previous exposition of mosquitoes to CxFV might lessen
      the susceptibility of these mosquitoes to other flaviviruses.

PMID- 22854126
TI  - Enhancement of peripheral blood CD56(dim) cell and NK cell cytotoxicity in women
      with recurrent spontaneous abortion or in vitro fertilization failure.
AB  - Recent studies support the concept that NK cells play an important role in the
      success or failure of embryo implantation. Recurrent spontaneous abortion (RSA)
      is the most common complication of pregnancy. Some couples suffer from
      infertility of unknown cause. In vitro fertilization (IVF) is one of the useful
      treatment methods used for treatment of this type for infertility with variable
      outcomes. The aim of this study was to compare the percentage of peripheral blood
      CD56(+) (CD56(dim) and CD56(bright)) cells and the level of NK cell cytotoxicity
      in patients with RSA and patients with IVF failure with those of healthy
      multiparous and successful IVF control women. In this case-control study
      peripheral blood samples from 43 patients, which included 23 women with RSA and
      20 with IVF failure, plus 43 healthy control women comprising 36 normal
      multiparous women and 7 women with successful IVF, were collected. The percentage
      of peripheral blood NK cells (CD56(+)) was identified by flow cytometry, then
      peripheral blood mononuclear cells (PBMC) were isolated by density centrifugation
      (Ficol-Hypaque) and incubated with NK-sensitive K562 cells. The NK cell
      cytotoxicity level was determined by lactate dehydrogenase (LDH) release assay.
      The percentage of CD56(dim) cells and the level of peripheral blood NK cell
      cytotoxicity in RSA patients and women with IVF failure were significantly higher
      than in both the healthy multiparous and successful IVF control groups (P<0.001).
      The findings of the present study suggest that increases in the percentage of
      CD56(dim) cells and NK cytotoxicity in peripheral blood may be important
      contributing factors for both RSA and IVF failure.

PMID- 22854127
TI  - High-performance liquid chromatography/tandem mass spectrometry for simultaneous
      determination of four dicaffeoylquinic acids in rat plasma.
AB  - A specific and reliable HPLC-MS/MS method was developed and validated for the
      simultaneous determination of four dicaffeoylquinic acids (DCQA): 3,4-DCQA, 1,5
      DCQA, 3,5-DCQA and 4,5-DCQA. The analytes were separated on a C18 column (150 mm
      * 2.1 mm, 1.8 MUm) and a triple-quadrupole mass spectrometry equipped with an
      electrospray ionization (ESI) source was applied for detection. The plasma sample
      was prepared by a liquid-liquid extraction method and the recovery for the four
      analytes was around 80%. The calibration curves were linear over a concentration
      range of 10.6-1060.0 ng/mL for 3,4-DCQA, 19.2-1920.0 ng/mL for 1,5-DCQA, 14.0
      2900.0 ng/mL for 3,5-DCQA, 9.7-970.0 ng/mL for 4,5-DCQA. The intra-day and inter
      day precision was less than 15% and the relative error (RE) were all within +/
      15%. The validated method was successfully applied to a pharmacokinetics study in
      rats after oral administration of the extracts of Ainsliaea fragrans cham (a
      traditional Chinese herb).

PMID- 22854128
TI  - Antibiotic impregnated catheter coverage of deep brain stimulation leads
      facilitates lead preservation after hardware infection.
AB  - Deep brain stimulation (DBS) has become a reliable and effective treatment for
      many disorders. However, the risk of long-term hardware-related complications is
      notable, and most concerning is hardware-related infections. Given the risk of
      hardware removal in the setting of infection, we retrospectively examined the
      implementation of a novel technique using antibiotic covered catheter protection
      of DBS leads after infection. The effect on hardware salvage and ease of
      reimplantation of the DBS extension and implantable pulse generator (IPG) was
      examined. A total of nine (9%) out of 100 DBS patients met the inclusion criteria
      with 11 DBS hardware-related infections at either the frontal, parietal, or IPG
      sites, from June 2003 to November 2010, at our institution. Subsequent to the
      initial patient in the series, a total of eight patients had placement of a short
      segment (approx. 4 cm long) of antibiotic impregnated catheter (Bactiseal,
      Codman, Johnson & Johnson, Raynham, MA, USA) over the distal end of the DBS leads
      at the parietal incision. Seven of these eight patients presented with pus and
      deep tissue infections around the hardware at either the frontal, parietal, or
      chest incisions. In seven of these eight patients (87.5%) we were able to protect
      and salvage their DBS leads without need for removal. In conclusion, this novel
      technique provides a simple reimplantation operation, with a decreased risk of
      DBS lead damage. It may improve the preservation of DBS leads when hardware
      infection occurs, is inexpensive, and confers no additional risks to patients.

PMID- 22854129
TI  - Incidence and severity of Arcanobacterium pyogenes injection site abscesses with
      needle or needle-free injection.
AB  - Nursery-age pigs (n=198) were used to evaluate the difference in abscess
      formation at needle-free jet and conventional needle-and-syringe injection sites.
      Needle-free jet injection was used to administer injections in the neck and ham
      on one side of the animal whereas needle-and-syringe was used for neck and ham
      injections on the opposite side. Immediately prior to injection, the injection
      site surfaces were contaminated with an inoculum of Arcanobacterium pyogenes.
      Each pig was humanely euthanized 27 or 28 days after injections.
      Histopathological results showed that needle-free jet injection was associated
      with more abscesses than needle-and-syringe injection at both neck (P=0.0625) and
      ham (P=0.0313) injection sites. Out of 792 injection sites, only 13 abscesses
      were observed, with 12 of those present at needle-free jet injection sites.
      Needle-free jet injection may increase the occurrence of injection site abscesses
      that necessitate carcass trimming at pork processing plants.

PMID- 22854130
TI  - Impact of the redox mediator sodium anthraquinone-2,6-disulphonate (AQDS) on the
      reductive decolourisation of the azo dye Reactive Red 2 (RR2) in one- and two
      stage anaerobic systems.
AB  - This work assessed the impact of the redox mediator sodium anthraquinone-2,6
      disulphonate (AQDS) on the reductive decolourisation of the azo dye Reactive Red
      2 (RR2) in one- and two-stage anaerobic systems (R(1) and R(2), respectively).
      The two-stage system achieved better colour removal efficiencies (52-62%) than
      the single-stage system (23-33%) in the absence of AQDS. Addition of AQDS
      accelerated the electrons transfer from the substrate (ethanol) to the dye, which
      increased the colour removal efficiency of both anaerobic systems (~ 85%).
      Finally, the impact of acidogenic and methanogenic phases separation was masked
      by AQDS supplementation.

PMID- 22854131
TI  - Producing high sugar concentrations from loblolly pine using wet explosion
      pretreatment.
AB  - We present quantitative analysis of pretreatment for obtaining high conversion
      and release of sugars from loblolly pine. We use wet explosion (WEx): wet
      oxidation followed by steam explosion and enzymatic hydrolysis (EH) at high dry
      matter to solubilize sugars. WEx was conducted at 25% (w/w) solids in presence of
      oxygen at pressures 6.5-7.2 bar, temperatures 170-175 degrees C and residence
      time from 20 to 22.5 min. EH of pretreated samples was performed by Cellic(r)
      Ctec2 (60 mg protein/g cellulose) and Cellic(r) Htec2 enzymes (10% of Ctec2) at
      50 degrees C for 72 h. At the optimal WEx condition 96% cellulose and nearly 100%
      hemicellulose yield were obtained. The final concentrations of monomeric sugars
      were 152 g/L of glucose, 67 g/L of xylose, and 67 g/L of minor sugars (galactose,
      arabinose and mannose). Compared to previous work WEx seems to be superior for
      releasing high concentrations of monomeric sugars.

PMID- 22854132
TI  - Laccase/HBT and laccase-CBM/HBT treatment of softwood kraft pulp: impact on pulp
      bleachability and physical properties.
AB  - Pycnoporus cinnabarinus laccase and a chimeric laccase-CBM were applied in
      softwood kraft pulp biobleaching in the presence of 1-hydroxybenzotriazole (HBT).
      The presence of CBM could enhance the laccase biobleaching potential as a
      decrease in the enzymatic charge and chlorine dioxide consumption, as well as an
      increase in pulp brightness were observed. Laccase/HBT treatment could be
      improved by increasing oxygen pressure from 1 to 3bar and pulp consistency from
      5% to 10%. Conversely, under the same conditions, no improvement of laccase
      CBM/HBT treatment was observed, indicating a different behavior of both systems.
      However, laccase-CBM/HBT treatment led to a better preservation of pulp
      properties. This effect was probably due to fiber surface modifications involving
      the action of the CBM. Transmission electron microscopy examination of pulp
      fibers indicated a retention of laccase-CBM inside the pulp fibers due to CBM
      binding and an increased external microfibrillation of the fibers due to
      enzymatic treatments.

PMID- 22854133
TI  - Development and validation of novel enzyme activity methods to assess inhibition
      of matrix metalloproteinases (MMPs) in human serum by antibodies against enzyme
      therapeutics.
AB  - This paper summarizes the development and validation of five enzyme activity
      methods to assess the specific inhibition of human endogenous matrix
      metalloproteinases MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3
      (stromelysin 1), MMP-8 (collagenase 2) and MMP-13 (collagenase 3) by anti
      Collagenase Clostridium histolyticum (CCH) antibodies in human serum. These MMPs
      are of interest since antibodies against a therapeutic enzyme may cross-react
      with, and inactivate, the MMPs. The validated methods utilize spiked exogenous
      individual MMPs added to serum to determine if the serum inhibits MMP enzyme
      activity. Factors evaluated and optimized during development include pH, reaction
      time and temperature, inhibitor concentration for the positive control, and
      substrate and serum concentration. Characteristics established during validation
      for each MMP activity inhibition method included intra- and inter-assay precision
      and recovery, recovery in the pooled normal human serum samples, bench-top
      stability at room temperature and on wet ice, and assay cut-point determination.
      Precision results ranged from ~1 to 12% CV, recoveries of the activities of the
      exogenous MMPs ranged from ~84 to 90% and cut-point values ranged from 67 to 91%.

PMID- 22854134
TI  - Predicting the histology of small renal masses using preoperative dynamic
      contrast-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To study whether magnetic resonance imaging can predict the histologic
      type of small renal cell carcinoma. METHODS: Dynamic contrast-enhanced magnetic
      resonance imaging was performed in 63 patients with computed tomography- or
      ultrasonography-suspected small (<= 4 cm) renal cell carcinoma from February 2008
      to February 2010. Percentage signal intensity change, tumor-to-cortex enhancement
      index during precontrast phase, corticomedullary phase, and nephrogenic phase
      were investigated. RESULTS: Among the 60 patients, 42 were proven to have clear
      cell renal cell carcinoma and 18 patients were proven to have non-clear cell
      renal cell carcinoma (10 patients with papillary renal cell carcinoma, 8 patients
      with chromophobe renal cell carcinoma). The percentage signal intensity change in
      the clear cell type was higher only in the corticomedullary phase (P = .002). The
      tumor-to-cortex enhancement index in the clear cell type was higher in the
      corticomedullary and nephrogenic phases (P = .007 and P = .041, respectively).
      The most valuable marker was percentage signal intensity change in the
      corticomedullary phase (area under the receiver operating characteristic curve
      0.85). The cut-off value of percentage signal intensity change in the
      corticomedullary phase was 173%, and the sensitivity and specificity were 81% and
      87.5%, respectively. CONCLUSION: Dynamic contrast-enhanced magnetic resonance
      imaging could be useful for discriminating the clear cell type from non-clear
      cell type in small renal cell carcinoma with high sensitivity and specificity.

PMID- 22854135
TI  - Editorial comment.

PMID- 22854136
TI  - Characterization of patients with heterozygous cystinuria.
AB  - OBJECTIVE: To characterize a contemporary cohort of patients with heterozygous
      (TZ) cystinuria and compare them with a concurrent cohort of patients with
      homozygous (MZ) cystinuria. METHODS: A retrospective review of prospectively
      collected data was performed for 42 consecutive patients presenting with a
      positive cyanide-nitroprusside test from September 2009 to September 2011.
      Clinical data were collected, including the findings from a detailed metabolic
      stone workup that included two 24-hour urine collections with quantitative
      cystine. The patients were divided into 2 groups: those with TZ (30-400 mg/d) and
      those with MZ (>400 mg/d) cystinuria. RESULTS: One patient was excluded because
      the cystine excretion was within the normal range (<30 mg/d), 35 (83.3%) and 6
      (14.3%) had TZ and MZ cystinuria, respectively. Compared with those with TZ
      cystinuria, those with MZ cystinuria were significantly younger at the first
      stone episode (median 48 years, range 14-67, vs 17, range 6-44, P = .002), more
      were female (20% vs 66.7%; P = .03), and more patients had bilateral stones (8.6%
      vs 50%; P = .03). Finally, the patients with MZ cystinuria had more stone
      episodes than those with TZ cystinuria (3 vs 1; P = .04). From the detailed
      metabolic stone evaluation, the incidence of hyperuricemia was significantly
      greater in the MZ patients (17.1% vs 66.7%; P = .02). Although all the MZ
      patients developed pure cystine stones, 18 (51.4%), 7 (20.0%), and 3 (8.6%) of
      the TZ patients developed calcium oxalate, uric acid, and cystine stones,
      respectively (P < .001). In the TZ group, 11 patients (31.4%) had false-negative
      results on subsequent cyanide-nitroprusside testing. CONCLUSION: Significant
      differences were found between the patients with TZ and MZ cystinuria in terms of
      age at the first stone episode, male/female ratio, incidence of hyperuricemia,
      and stone composition. The clinical significance remains to be elucidated.

PMID- 22854137
TI  - Is fluoroscopic imaging mandatory for endoscopic treatment of ureteral stones?
AB  - OBJECTIVE: To present the feasibility and safety of fluoro-less endoscopic
      treatment of ureteral stones to diminish radiation exposure of the patient and
      operating team, and to determine circumstances where a fluoroscopic imaging is
      mandatory. METHODS: Between 2010 and 2011, 93 patients with ureteral calculi who
      underwent ureteroscopic treatment by experienced urologists were retrospectively
      evaluated. Manipulations, such as guidewire, ureteral stent insertion, and
      balloon dilatation were performed with visual and tactile cues. Patient
      demographics, need for fluoroscopic imaging, operation and fluoroscopy time, and
      complication and success rates were investigated. RESULTS: The mean age of
      patients was 34.03 +/- 12.09 years (range, 9-63 years). The mean stone size was
      10.64 +/- 3.16 mm (range, 6-17 mm). The stones were localized in the proximal,
      middle, and distal segments in 11, 30, and 52 patients, respectively. The mean
      duration of the operation was 34.51 +/- 7.94 minutes (range, 24-55 minutes).
      Stone-free status was achieved for 90 patients (96.77%). Fluoroscopic imaging was
      required for 7 patients with a mean fluoroscopy time of 9 +/- 4.72 seconds
      (range, 4-16 seconds) for the following reasons: stone migration to the kidney (3
      patients), double collecting system with 2 ureters (1 patient), and ureteral
      orifice stricture extending to the upper segment (1 patient). No major
      complications were observed, but minor complications were observed in 11 patients
      (11.8%). CONCLUSION: The ureteroscopic treatment of ureteral stones can be safely
      and effectively performed in experienced hands, with limited or no usage of
      fluoroscopy except in special circumstances, such as anatomic abnormalities,
      upper ureteral strictures, and impacted ureteral stones leading to ureteral
      tortuosity, kinking, and obstruction.

PMID- 22854138
TI  - Urodynamic effects of transrectal intraprostatic Ona botulinum toxin A injections
      for symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate urodynamic, symptomatic, and histologic effects of
      intraprostatic injection with Ona botulinum toxin A for benign prostatic
      hyperplasia. METHODS: Patients >55 years with symptomatic benign prostatic
      hyperplasia failing medical therapy were treated. Inclusion criteria were
      International Prostate Symptom Score >7, prostate volume 30-50 cm(3), and
      urodynamic bladder outlet obstruction >Schafer grade 2. A transrectal
      intraprostatic injection of 200 IU Ona botulinum toxin A was given. Filling
      cystometry and pressure flow studies were performed at 3, 6, and 12 months post
      injection. International Prostate Symptom Score, International Prostate Symptom
      Score quality of life, prostate-specific antigen, and prostate volume were
      measured up until 12 months; prostate biopsies before and after Ona botulinum
      toxin A injection were done for histology and cell proliferation. RESULTS:
      Fifteen men (mean age 64.9 years) were included. Ona botulinum toxin A injection
      was well tolerated with few complications. Postvoid residual improved (170 to 80
      mL), but maximum flow rate and bladder outlet resistance parameters did not
      change during follow-up. International Prostate Symptom Score and International
      Prostate Symptom Score quality of life improved (22 to 13 and 5 to 2,
      respectively), whereas prostate-specific antigen and prostate volume remained
      unaltered. Cell proliferation did not decrease and in 37% and 64% of pre- and
      posttreatment biopsies, respectively, some degree of prostatitis was found. Ten
      of 15 patients eventually underwent transurethral prostate resection because of
      persisting symptoms. CONCLUSION: Intraprostatic Ona botulinum toxin A for
      symptomatic benign prostatic hyperplasia did not affect urodynamic outcomes,
      except for postvoid residual. Although symptom scores improved, we were not able
      to show change in prostate volume, prostate-specific antigen, or histologic
      outcomes. A placebo effect of intraprostatic Ona botulinum toxin A could not be
      ruled out.

PMID- 22854139
TI  - Infantile fibrosarcoma of the penis in a 2-year-old boy.
AB  - Fibrosarcoma is rare in the pediatric age group. It generally involves the
      extremities and the trunk but rarely involves the genital area. We report a case
      of a large fungating infantile fibrosarcoma of the penis in a 2-year-old Malay
      boy. Partial recovery of the penile structure was achieved after chemotherapy.
      The difficulty in managing the social and surgical aspect of this case is
      discussed in our report. To the best of our knowledge, this is the first case
      report of infantile fibrosarcoma involving the penis in an Asian region.

PMID- 22854140
TI  - Effect of stone composition on operative time during ureteroscopic
      holmium:yttrium-aluminum-garnet laser lithotripsy with active fragment retrieval.
AB  - OBJECTIVE: To assess whether the stone composition affects the operative time of
      ureteroscopic holmium:yttrium-aluminum-garnet laser lithotripsy (ULL) with active
      fragment retrieval. The chemical composition of a calculus is known to affect the
      efficacy with which it is fragmented by a device, such as pneumatic, laser, or
      shock wave lithotripter. Previous studies examining the efficacy of
      holmium:yttrium-aluminum-garnet laser lithotripsy have been performed in vitro,
      but it is not known whether the operative time is significantly affected by the
      chemical composition of a patient's stone. METHODS: We selected all patients who
      had undergone ULL for stone disease from July 2008 to January 2011 for a
      retrospective chart review. We used a standardized operative technique of
      fragmentation and active retrieval of all fragments identified on full inspection
      of the entire collecting system using rigid and flexible endoscopes. The stone
      composition was defined as the presence of a single predominant (>51%) component.
      Statistical analysis was performed on a per-procedure basis relative to the stone
      burden, as measured in minutes of operative time per gram of stone. RESULTS: A
      total of 187 cases of unilateral ULL with active retrieval of stone fragments
      confirmed to have a single predominant chemical composition met the inclusion
      criteria. When accounting for the weight of the recovered stone, no difference
      was found in the operative time among the apatite, brushite, cystine, calcium
      oxalate monohydrate, calcium oxalate dihydrate, and uric acid stones. CONCLUSION:
      Although stone composition is widely recognized as an important procedural
      variable, especially for shock wave lithotripsy, it appears to have little effect
      on the overall operative time for holmium:yttrium-aluminum-garnet lithotripsy
      when using active fragment retrieval.

PMID- 22854141
TI  - Editorial comment.

PMID- 22854142
TI  - Preparing Canadian surgeons to provide care in the 21st century.

PMID- 22854144
TI  - Does operative experience during residency correlate with reported competency of
      recent general surgery graduates?
AB  - BACKGROUND: Identification of attributes of residency training that predict
      competency would improve surgical education. We hypothesized that case experience
      during residency would correlate with self-reported competency of recent
      graduates. METHODS: Aggregate case log data of residents enrolled in 2 general
      surgery programs were collected over a 12-month period and stratified into
      Surgical Council on Resident Education (SCORE) categories. We surveyed recent (<
      5 yr) residency graduates on procedural competency. Resident case volumes were
      correlated with survey responses by SCORE category. RESULTS: In all, 75 residents
      performed 11 715 operations, which were distributed by SCORE category as follows:
      essential-common (EC) 9935 (84.8%), essential-uncommon (EU) 889 (7.6%) and
      complex 891 (7.6%). Alimentary tract procedures were the most commonly performed
      EC (2386, 24%) and EU (504, 56.7%) procedures. The least common EC procedure was
      plastic surgery (4, 0.04%), and the least common EU procedure was abdomen-spleen
      (1, 0.1%). The questionnaire response rate was 45%. For EC procedures, self
      reported competency was highest in skin and soft tissue, thoracic and head and
      neck (each 100%) and lowest in vascular-venous (54%), whereas for EU procedures
      it was highest in abdomen-general (100%) and lowest in vascular-arterial (62%).
      The correlation between case volume and self-reported competency was poor (R =
      0.2 for EC procedures). CONCLUSION: Self-reported competency correlates poorly
      with operative case experience during residency. Other curriculum factors,
      including specific rotations and timing, balance between inpatient and outpatient
      surgical experience and competition for cases, may contribute to procedural
      competency acquisition during residency.

PMID- 22854145
TI  - Sharps-handling practices among junior surgical residents: a video analysis.
AB  - BACKGROUND: Although "universal precautions" are standard for sharps handling,
      there has been poor compliance among surgeons. We used video analysis to assess
      sharps handling practices among junior surgical residents. METHODS: Postgraduate
      year (PGY)-2 general surgery and PGY-1 plastic surgery residents were videotaped
      performing pediatric inguinal hernia repairs. For each procedure, the resident
      was the principal operator, with the attending surgeon assisting. Retrospective
      assessment of safe and unsafe sharps handling was determined based on published
      guidelines. We assessed safety performance in personal sharps tasks, passage of
      sharps and verbal notification regarding sharps. Data was analyzed using
      descriptive statistics. RESULTS: Data were collected from 18 residents' videos (4
      plastic surgery, 14 general surgery). Residents safely performed sharps tasks,
      passed and verbally notified about sharps an average of 69.2%, 93.2% and 9.9% of
      the time, respectively. Suture needle manipulation was handled safely 56.2% of
      the time (mean 4.4 safe v. 4.3 unsafe actions). Surgical residents demonstrated a
      safe suture tying technique in 91.8% of cases, proper tissue retraction in 85.2%
      and safe handling of injection needles in 72.2% of cases. When assessing the
      safety performance of the surgical team, attending surgeons acting as surgical
      assistants safely passed sharps 80.0% of the time, while scrub nurses
      demonstrated safe passing at all times. Attending surgeons used verbal
      notification when passing sharps 22.7% of the time, while scrub nurses verbally
      notified the team 4.3% of the time. CONCLUSION: Junior surgical residents
      consistently passed sharps safely. Personal sharps tasks were less likely to be
      performed safely, and only a minority of residents verbally notified the team
      about sharps placement.

PMID- 22854146
TI  - The Canadian general surgery resident: defining current challenges for surgical
      leadership.
AB  - BACKGROUND: Surgery training programs in Canada and the United States have
      recognized the need to modify current models of training and education. The
      shifting demographic of surgery trainees, lifestyle issues and an increased trend
      toward subspecialization are the major influences. To guide these important
      educational initiatives, a contemporary profile of Canadian general surgery
      residents and their impressions of training in Canada is required. METHODS: We
      developed and distributed a questionnaire to residents in each Canadian general
      surgery training program, and residents responded during dedicated teaching time.
      RESULTS: In all, 186 surveys were returned for analysis (62% response rate). The
      average age of Canadian general surgery residents is 30 years, 38% are women, 41%
      are married, 18% have dependants younger than 18 years and 41% plan to add to or
      start a family during residency. Most (87%) residents plan to pursue postgraduate
      education. On completion of training, 74% of residents plan to stay in Canada and
      49% want to practice in an academic setting. Almost half (42%) of residents
      identify a poor balance between work and personal life during residency. Forty
      seven percent of respondents have appropriate access to mentorship, whereas 37%
      describe suitable access to career guidance and 40% identify the availability of
      appropriate social supports. Just over half (54%) believe the stress level during
      residency is manageable. CONCLUSION: This survey provides a profile of
      contemporary Canadian general surgery residents. Important challenges within the
      residency system are identified. Program directors and chairs of surgery are
      encouraged to recognize these challenges and intervene where appropriate.

PMID- 22854147
TI  - Canadian Association of University Surgeons' Annual Symposium. Surgical
      simulation: the solution to safe training or a promise unfulfilled?
AB  - At its 2009 annual symposium, chaired by Dr. William (Bill) Pollett, the Canadian
      Association of University Surgeons brought together speakers with expertise in
      surgery and medical education to discuss the role of surgical simulation for
      improving surgical training and safety. Dr. Daniel Jones, of Harvard University
      and the 2009 Charles Tator Lecturer, highlighted how simulation has been used to
      teach advanced laparoscopic surgery. He also outlined how the American College of
      Surgeons is moving toward competency assessments as a requirement before surgeons
      are permitted to perform laparoscopic surgery on patients. Dr. Teodor
      Grantcharov, from the University of Toronto, highlighted the role of virtual
      reality simulators in laparoscopic surgery as well as box trainers. Dr. Peter
      Brindley from the University of Alberta, although a strong proponent of
      simulation, cautioned against an overzealous adoption without addressing its
      current limitations. He also emphasized simulation's value in team training and
      crisis resource management training. Dr. Chris de Gara, also from the University
      of Alberta, questioned to what extent simulators should be used to determine
      competency. He raised concerns that if technical skills are learned in isolation,
      they may become "decontextualized," and therefore simulation might become
      counterproductive. He outlined how oversimplification can have an "enchanting"
      effect, including a false sense of security. As a result, simulation must be used
      appropriately and along the entire education continuum. Furthermore, far more
      needs to be done to realize its role in surgical safety.

PMID- 22854148
TI  - Management of chest tubes after pulmonary resection: a systematic review and meta
      analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis to determine the
      effect of suction with water seal, compared with water seal alone, applied to
      intra pleural chest tubes on the duration of air leaks in patients undergoing
      pulmonary surgery. METHODS: We searched MEDLINE, EMBASE and the Cochrane Central
      Register of Controlled Trials to find randomized controlled trials (RCTs)
      comparing the effect of the 2 methods on the duration of air leaks. Trials were
      systematically assessed for eligibility and validity. Data were extracted in
      duplicate and pooled across studies using a random-effects model. RESULTS: The
      search yielded 7 RCTs that met the eligibility criteria. No difference was
      identified between the 2 methods in duration of air leak (weighted mean
      difference [WMD] 1.15 days, favours water seal; 95% confidence interval [CI] 
      0.64 to 2.94), time to discharge (WMD 2.19 d, favours water seal; 95% CI -0.63 to
      5.01), duration of chest tubes (WMD 0.96 d, favours water seal; 95% CI -0.12 to
      2.05) or incidence of prolonged air leaks (absolute risk reduction [ARR] 0.04,
      favours water seal; 95% CI -0.01 to 0.09). Water seal was associated with a
      significantly increased incidence of postoperative pneumothorax (ARR -0.14, 95%
      CI -0.21 to -0.07). CONCLUSION: No differences were identified in terms of
      duration of air leak, incidence of prolonged air leak, duration of chest tubes
      and duration of hospital stay when chest tubes were placed to suction rather than
      water seal. Chest tube suction appears to be superior to water seal in reducing
      the incidence of pneumothorax; however, the clinical significance of this finding
      is unclear.

PMID- 22854149
TI  - 1 Canadian Field Hospital in Haiti: surgical experience in earthquake relief.
AB  - The Canadian Forces' (CF) deployable hospital, 1 Canadian Field Hospital, was
      deployed to Haiti after an earthquake that caused massive devastation. Two
      surgical teams performed 167 operations over a 39-day period starting 17 days
      after the index event. Most operations were unrelated to the earthquake.
      Replacing or supplementing the destroyed local surgical capacity for a brief
      period after a disaster can be a valuable contribution to relief efforts. For
      future humanitarian operations/disaster response missions, the CF will study the
      feasibility of accelerating the deployment of surgical capabilities.

PMID- 22854151
TI  - Is Canadian surgical residency training stressful?
AB  - BACKGROUND: Surgical residency has the reputation of being arduous and stressful.
      We sought to determine the stress levels of surgical residents, the major causes
      of stress and the coping mechanisms used. METHODS: We developed and distributed a
      survey among surgical residents across Canada. RESULTS: A total of 169
      participants responded: 97 (57%) male and 72 (43%) female graduates of Canadian
      (83%) or foreign (17%) medical schools. In all, 87% reported most of the past
      year of residency as somewhat stressful to extremely stressful, with time
      pressure (90%) being the most important stressor, followed by number of working
      hours (83%), residency program (73%), working conditions (70%), caring for
      patients (63%) and financial situation (55%). Insufficient sleep and frequent
      call was the component of residency programs that was most commonly rated as
      highly stressful (31%). Common coping mechanisms included staying optimistic
      (86%), engaging in enjoyable activities (83%), consulting others (75%) and
      exercising (69%). Mental or emotional problems during residency were reported
      more often by women (p = 0.006), who were also more likely than men to seek help
      (p = 0.026), but men reported greater financial stress (p = 0.036). Foreign
      graduates reported greater stress related to working conditions (p < 0.001),
      residency program (p = 0.002), caring for family members (p = 0.006),
      discrimination (p < 0.001) and personal and family safety (p < 0.001) than
      Canadian graduates. CONCLUSION: Time pressure and working hours were the most
      common stressors overall, and lack of sleep and call frequency were the most
      stressful components of the residency program. Female sex and graduating from a
      non-Canadian medical school increased the likelihood of reporting stress in
      certain areas of residency.

PMID- 22854152
TI  - Resident self-assessment of operative experience in primary total knee and total
      hip arthroplasty: Is it accurate?
AB  - BACKGROUND: A prerequisite for a valuable surgical case log is the ability to
      perform an accurate self-assessment. Studies have shown mixed results when
      examining residents' ability to self-assess on varying tasks. We sought to
      examine the correlation between residents' self-assessment and staff surgeons'
      evaluation of surgical involvement and competence in performing primary total
      knee (TKA) and hip arthroplasty (THA). METHODS: We used the intraclass
      correlation coefficient (ICC) to evaluate interobserver agreement between
      residents' self-perception and staff surgeons' assessment of involvement. An
      assessment of competency was performed using a categorical global scale and
      evaluated with the kappa statistic. We piloted a structured surgical skills
      assessment form as an additional objective appraisal of resident involvement.
      RESULTS: We analyzed assessment data from 65 primary TKA and THA cases involving
      17 residents and 17 staff surgeons (93% response rate). The ICC for resident
      involvement between residents and staff surgeons was 0.80 (95% confidence
      interval [CI] 0.69-0.88), which represents substantial agreement. The agreement
      between residents and staff surgeons about residents' competency to perform the
      case had a kappa value of 0.67 (95% CI 0.50-0.84). The ICC for resident, staff
      surgeon and third-party observer using the piloted skills assessment form was
      0.82 (95% CI 0.75-0.88), which represents substantial agreement. CONCLUSION: This
      study supports the ability of orthopedic residents to perform self-assessments of
      their degree of involvement and competency in primary TKA and THA. Staff
      surgeons' assessment of resident involvement correlated highly with the surgical
      skills assessment form. Self-assessment is a valuable addition to the surgical
      case log.

PMID- 22854153
TI  - Knowing the operative game plan: a novel tool for the assessment of surgical
      procedural knowledge.
AB  - BACKGROUND: What is the source of inadequate performance in the operating room?
      Is it a lack of technical skills, poor judgment or a lack of procedural
      knowledge? We created a surgical procedural knowledge (SPK) assessment tool and
      evaluated its use. METHODS: We interviewed medical students, residents and
      training program staff on SPK assessment tools developed for 3 different common
      general surgery procedures: inguinal hernia repair with mesh in men, laparoscopic
      cholecystectomy and right hemicolectomy. The tools were developed as a step-wise
      assessment of specific surgical procedures based on techniques described in a
      current surgical text. We compared novice (medical student to postgraduate year
      [PGY]-2) and expert group (PGY-3 to program staff) scores using the Mann-Whitney
      U test. We calculated the total SPK score and defined a cut-off score using
      receiver operating characteristic analysis. RESULTS: In all, 5 participants in 7
      different training groups (n = 35) underwent an interview. Median scores for each
      procedure and overall SPK scores increased with experience. The median SPK for
      novices was 54.9 (95% confidence interval [CI] 21.6-58.8) compared with 98.05
      (95% CP 94.1-100.0) for experts (p = 0.012). The SPK cut-off score of 93.1
      discriminates between novice and expert surgeons. CONCLUSION: Surgical procedural
      knowledge can reliably be assessed using our SPK assessment tool. It can
      discriminate between novice and expert surgeons for common general surgical
      procedures. Future studies are planned to evaluate its use for more complex
      procedures.

PMID- 22854154
TI  - Long-term outcomes for surgeons from 3- and 4-year medical school curricula.
AB  - BACKGROUND: New approaches are needed to ensure that surgical trainees attain
      competence in a timely way. Traditional solutions have focused on the years spent
      in surgic al training. We sought to examine the outcomes of graduates from 3-year
      versus 4-year medical schools for differences in surgeon performance based on
      multisource feedback data. METHODS: We used data from the College of Physicians
      and Surgeons of Alberta's Physician Achievement Review program to determine
      curricular outcomes. Data for each surgeon included assessments from 25 patients,
      8 medical colleagues and 8 nonphysician coworkers (e.g., nurses), and a self
      assessment. We used these data to compare 72 physicians from a 3-year school
      matched with graduates from 4-year schools. The instruments were assessed for
      evidence of validity and reliability. We compared the groups using 1-way analysis
      of covariance and multivariate analysis of covariance, with years since
      graduation as a covariate, and a Cohen d effect size calculation to assess the
      magnitude of the change. RESULTS: Data for 216 surgeons indicated that there was
      evidence for instrument validity and reliability. No significant differences were
      found based on the length of the undergraduate program for any of the
      questionnaires or factors within the questionnaires. CONCLUSION: Reconsideration
      might be given to the time spent in medical school before surgical training if
      training in the specialty and career years are to be maximized. This assumes that
      students are able to make informed career decisions based on clerkship and other
      experiences in a 3-year setting.

PMID- 22854155
TI  - Surgical residency training and international volunteerism: a national survey of
      residents from 2 surgical specialties.
AB  - BACKGROUND: Many low- and middle-income countries (LMICs) lack basic surgical
      resources, resulting in avoidable disability and mortality. Recently, residents
      in surgical training programs have shown increasing interest in overseas elective
      experiences to assist surgical programs in LMICs. The purpose of this study was
      to survey Canadian surgical residents about their interest in international
      volunteerism. METHODS: We sent a web-based survey to all general and orthopedic
      surgery residents enrolled in surgical training programs in Canada. The survey
      assessed residents' interests, attitudes and motivations, and perceived barriers
      and aids with respect to international volunteerism. RESULTS: In all, 361
      residents completed the survey for a response rate of 38.0%. Half of the
      respondents indicated that the availability of an international surgery elective
      would have positively influenced their selection of a residency program.
      Excluding the 18 residents who had volunteered during residency, 63.8% of the
      remaining residents confirmed an interest in international volunteering with
      "contributing to an important cause," "teaching" and "tourism/cultural
      enhancement" as the leading reasons for their interest. Perceived barriers
      included "lack of financial support" and "lack of available organized
      opportunities." All (100%) respondents who had done an international elective
      during residency confirmed that they would pursue such work in the future.
      CONCLUSION: Administrators of Canadian surgical programs should be aware of
      strong resident interest in global health care and accordingly develop
      opportunities by encouraging faculty mentorships and resources for global health
      teaching.

PMID- 22854157
TI  - The change in cervical length over time as a predictor of preterm delivery in
      asymptomatic women with twin pregnancies who have a normal mid-trimester cervical
      length.
AB  - AIM: To determine whether or not the change in cervical length (CL) over time is
      valuable in predicting spontaneous preterm delivery (SPTD) in asymptomatic twin
      pregnancies with a normal mid-trimester CL (>25 mm). METHODS: This was a
      prospective study including 190 consecutive asymptomatic twin gestations with a
      CL>25 mm at 20-24 weeks. The women underwent an initial CL measurement at the
      time of routine ultrasound examination between 20 and 24 weeks' gestation,
      followed 4-5 weeks later by a repeat CL measurement. The primary outcome measure
      was SPTD at <32 completed weeks' gestation. Multicollinearity was a concern in
      the multivariable model since change in CL and follow-up CL were highly
      correlated. RESULTS: The rate of SPTD at <32 weeks was 4.2%. Multiple logistic
      regression analyses demonstrated that the change in CL and the follow-up CL were
      significantly associated with SPTD before 32 weeks after adjusting for baseline
      covariate such as in vitro fertilization. The best cut-off values for the
      prediction of SPTD at <32 weeks' gestation were 13% for the change in CL with a
      sensitivity of 87.5% and a specificity of 63.2%. There was no significant
      difference in the area under the receiver operating characteristic curves between
      the change in CL and the follow-up CL. CONCLUSIONS: A greater change in CL is a
      good predictor of SPTD in asymptomatic twin pregnancies with a normal mid
      trimester CL. However, the change in CL cannot provide data beyond the follow-up
      CL. In the setting of a normal mid-trimester CL, a follow-up CL measurement
      should be considered in asymptomatic twin pregnancies.

PMID- 22854158
TI  - Health information exchange interventions can enhance quality and continuity of
      HIV care.
AB  - PURPOSE: The purpose of this article is to describe how comprehensive HIV care is
      delivered within Ryan White Program (RWP)-funded clinics and to characterize
      proposed health information exchange (HIE) interventions, which employ technology
      to exchange information among providers, designed to improve the quality and
      coordination of clinical and support services. METHODS: We use HIV patient care
      quality and coordination indicators from electronic data systems to describe care
      delivery in six RWP demonstration sites and describe HIE interventions designed
      to enhance that care. RESULTS: Among patients currently in care, 91% were
      retained in care in the previous six months (range across sites: 63-99%), 79%
      were appropriately prescribed antiretroviral therapy (54-91%) and 52% had
      achieved undetectable HIV viral load (16-85%). To facilitate coordination of care
      across clinical and support services, sites designed HIE interventions to access
      a variety of data systems (e.g. surveillance, electronic health records,
      laboratory and billing) and focused on improving linkage and retention, quality
      and efficiency of care and increased access to patient information. DISCUSSION:
      Care quality in RWP settings can be improved with HIE tools facilitating linkage,
      retention and coordination of care. When fully leveraged, HIE interventions have
      the potential to improve coordination of care and thereby enhance patient health
      outcomes.

PMID- 22854159
TI  - Perceptions regarding the ease of use and usefulness of health information
      exchange systems among medical providers, case managers and non-clinical staff
      members working in HIV care and community settings.
AB  - PURPOSE: The objective of this paper is to describe how members of HIV patients'
      care teams perceived the usefulness and ease of use of newly implemented,
      innovative health information exchange systems (HIEs) in diverse HIV treatment
      settings. Five settings with existing electronic medical records (EMRs) received
      special funding to test enhancements to their systems. Participating clinics and
      community-based organizations added HIEs permitting bi-directional exchange of
      information across multiple provider sites serving the same HIV patient
      population. METHODS: We conducted in-depth qualitative interviews and
      quantitative web-based surveys with case managers, medical providers, and non
      clinical staff members to assess the systems' perceived usefulness and ease of
      use shortly after the HIEs were implemented. Our approach to data analysis was
      iterative. We first conducted a thematic analysis of the qualitative data and
      discovered that there were key differences in perceptions and actual use of HIEs
      across occupational groups. We used these results to guide our analysis of the
      quantitative survey data, stratifying by occupational group. RESULTS: We found
      differences in reports of how useful and how well-used HIEs were, by occupation.
      Medical providers were more likely to use HIEs if they provided easier access to
      clinical information than was present in existing EMRs. Case managers working
      inside medical clinics found HIEs to be less helpful because they already had
      access to the clinical data. In contrast, case managers working in community
      settings appreciated the new access to patient information that the HIEs
      provided. Non-clinical staff uniformly found the HIEs useful for a broad range of
      tasks including clinic administration, grant writing and generating reports for
      funders. CONCLUSION: Our study offers insights into the use and potential
      benefits of HIE in the context of HIV care across occupational groups.

PMID- 22854160
TI  - Differences in community, hospital and intensive care unit-acquired acute kidney
      injury: observational study in a nephrology service of a developing country.
AB  - BACKGROUND: Acute kidney injury (AKI) complicates more than 7% of all in-hospital
      patients. The aim of this study is to investigate the differences in community,
      hospital and intensive care unit-acquired AKI in patients undergoing nephrology
      consultation in a tertiary hospital in a developing country. METHODS: An
      observational cohort study of all patients with AKI admitted to the General
      Hospital of Fortaleza, Brazil was conducted. RIFLE criteria were used to classify
      the patients and to assess their association with death. Univariate and
      multivariate analyses were performed to investigate the factors associated with
      death. RESULTS: Of 491 AKI patients undergoing nephrology consultation, the mean
      age was 55.2 +/- 22.9 years. Community-acquired AKI was observed in 55% of cases,
      general ward-acquired in 29% and ICU-acquired in 15.3%. Late Nephrology
      consultation was observed, and the great majority of patients had "Failure"
      classification (90%) according to RIFLE criteria. Intermittent hemodialysis was
      required in 68% of cases. The overall in-hospital mortality was 23%. The in
      hospital mortality was higher in ICU-acquired AKI (33.6%). Community acquired AKI
      had a higher mortality than general ward-acquired AKI (23% vs. 11.6%, p = 0.001).
      Risk factors for death were infection (OR = 2.0, p = 0.003), neoplasms (OR =
      1.89, p = 0.042), community acquired-AKI (OR = 1.27, p = 0.003), ICU acquired-AKI
      (OR = 2.76, p < 0.0001) and need for renal replacement therapy (OR = 2.64, p <
      0.001). CONCLUSIONS: AKI is a frequent and frequently fatal condition. Mortality
      was higher in community and ICU-acquired than hospital ward-acquired AKI.

PMID- 22854161
TI  - Novel ATP6V0A4 mutation described in a Tunisian patient with distal renal tubular
      acidosis.
AB  - Few data regarding molecular diagnosis of primary distal renal tubular acidosis
      (DRTA) in Tunisian population are available. CASE REPORT: 25-day-old male patient
      from consanguineous parents of Tunisian origin diagnosed with DRTA and without
      hearing impairment observed later in life. ATP6V0A4 gene sequencing demonstrated
      a novel homozygous G deletion in exon 13 (c.1221delG, p.Met408CysfsX10), leading
      to a premature stop codon. CONCLUSION: A novel ATP6V0A4 gene mutation confirmed
      autosomal recessive DRTA with normal hearing in the patient. Molecular analysis
      may help to rapidly diagnose autosomal recessive DRTA in Tunisian population.

PMID- 22854162
TI  - The association between coronary artery calcification progression and loss of
      bone density in non-dialyzed CKD patients.
AB  - BACKGROUND: Coronary artery calcification (CAC) and low bone density are
      coexisting deleterious conditions commonly shared by chronic kidney disease (CKD)
      patients. In the present study, we aimed to investigate whether the progression
      of CAC was associated with overtime reduction in bone density in non-dialyzed CKD
      patients. METHODS: This is a prospective study of 24 months including 72 non
      dialyzed CKD patients Stages 2 - 4 (age 57.6 +/- 10.3 years, 62% male, 22%
      diabetics). CAC and vertebral bone density (VBD) were measured by computed
      tomography. RESULTS: At baseline, 46% of the patients had CAC (calcified group)
      and calcification was not identified in 54% of the patients (non-calcified
      group). The calcified group was older, predominantly male, and had lower VBD in
      comparison to non-calcified group. CAC progression was observed only in the
      calcified group (91% of the patients increased calcium score). The multiple
      regression analysis revealed loss of VBD as the independent determinant of CAC
      progression in these patients. CONCLUSIONS: CAC progression was associated with
      loss of VBD in non-dialyzed CKD patients.

PMID- 22854163
TI  - A case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis
      patient.
AB  - Ectopic parathyroid glands are detected occasionally, especially in cases of
      recurrent hyperparathyroidism after initial parathyroidectomy. Their ectopic
      locations usually result from faulty migration during embryogenesis. Ectopic
      parathyroid glands can be found within the thyroid gland, thymus, mediastinum,
      carotid sheath, or retropharynx, which lie along the path of their normal
      migration. Here we report a rare case of parathyroid adenoma adjacent to the
      thoracic spine in a hemodialysis patient who had undergone parathyroidectomy
      previously. A 67-year-old woman on maintenance hemodialysis since 1993 developed
      hyperparathyroidism. She underwent total parathyroidectomy with
      autotransplantation in 2007. Histological examination of the parathyroid glands
      showed hyperplasia in three glands and adenoma in one. Serum parathyroid hormone
      levels gradually increased after a year. Ultrasonography of the neck and upper
      limbs was negative, but technetium-99-sestamibi scanning showed focal uptake in
      the posterior mediastinum. Computed tomography and magnetic resonance imaging
      confirmed a tumor adjacent to the left costovertebral junction of the third
      thoracic vertebra. A tumor resection was performed in 2010, and histopathological
      examination showed a parathyroid adenoma. Parathyroid adenoma adjacent to the
      thoracic spine has not been reported previously, and our case suggests that
      technetium-9-sestamibi scanning is useful for the correct preoperative diagnosis
      of such rare cases of ectopic parathyroid glands. 

PMID- 22854164
TI  - Long-term multidrug therapy in an adolescent patient with proliferative lupus
      nephritis: a trial of less cytotoxic therapy.

PMID- 22854165
TI  - Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome.
AB  - Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular
      disorder resulting from inactivating mutations in the asolateral chloride channel
      (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate
      hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely
      rare, especially in middle age. A 45-year-old Chinese female patient was referred
      for evaluation of chronic severe hypokalemia despite regular K+ supplementation
      (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe
      hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting,
      diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal.
      Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium
      wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8
      mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22
      mmol/mol), high plasma renin activity, but normal plasma aldosterone
      concentration. Abdominal sonography revealed neither renal stones nor
      nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs
      were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and
      SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC),
      revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited
      from her parents; her SLC12A3 was normal. These two mutations were not identified
      in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after
      the addition of spironolactone. Inherited cBS may present with hypokalemic
      paralysis and should be considered in adult patients with hypokalemia and
      metabolic alkalosis. 

PMID- 22854166
TI  - Respiratory compensation to a primary metabolic alkalosis in humans.
AB  - There is limited and disparate information about the extent of the respiratory
      compensation (hypoventilation) that occurs in response to a primary metabolic
      alkalosis in humans. Our aim was to examine the influence of the plasma
      bicarbonate concentration, the plasma base excess, and the arterial pH on the
      arterial carbon dioxide tension in 52 adult patients with primary metabolic
      alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was
      used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In
      this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l,
      plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma
      bicarbonate and base excess correlated closely with arterial carbon dioxide
      tensions (r = 0.97 and 0.96, respectively; p < 0.0001), while there was little
      relationship between arterial pH and arterial carbon dioxide tensions (p = 0.08).
      The arterial carbon dioxide tension increased 1.2 torr for each 1.0 mEq/l
      increment in plasma bicarbonate or base excess (95% confidence interval, 1.1 -
      1.3 torr). This 1.2 torr increase amounts to a ~ 50% greater degree of
      respiratory compensation (hypoventilation) to primary metabolic alkalosis than
      has been reported in prior smaller studies.

PMID- 22854167
TI  - Castleman disease with preceding symptoms of nephrotic syndrome.

PMID- 22854168
TI  - Medial canthopexy using transcaruncular barb and miniplate: technique and cadaver
      study.
AB  - Traditional medial canthopexy techniques require transnasal access, periorbital
      skin incision, and/or direct canthal suturing, often yielding unpredictable
      outcomes. The transcaruncular canthal barb and miniplate technique is a
      simplified method of canthopexy that avoids these manoeuvres. 10 transcaruncular
      medial canthopexies were performed on cadavers with simulated naso-orbito-ethmoid
      (NOE) injury. Differences in mean pre-injury and post-canthopexy intercanthal
      distance (ICD) and palpebral aperture width (PAW) measurements were compared
      using a matched paired t test. Reliability between pre-injury and post-injury
      intercanthal distance and PAW was compared with intraclass correlation
      coefficients. Canalicular distortion and final implant position were assessed
      with post-canthopexy computed tomography (CT). There was no difference in mean
      palpebral aperture width (32.32 and 32.43 mm) or mean intercanthal distance
      (29.18 and 29.06 mm) between pre-injury and post-canthopexy groups (both p>0.05).
      All intercanthal distance and PAW intraclass correlation coefficients were >0.97
      (p<0.05). Post-canthopexy, CT scans showed canaliculus distortion in 4/10 of
      upper and 0/10 of lower canaliculi with all canthal barbs in the correct position
      relative to the plate. In a cadaver telecanthus model, medial canthopexy using
      the transcaruncular barb and miniplate technique reliably reduces the medial
      canthus and did not distort the lower lacrimal canaliculus, but may distort the
      upper canaliculus.

PMID- 22854169
TI  - Exhaled breath condensate in pulmonary arterial hypertension.
AB  - Over the last decade, several new agents have been developed for the treatment of
      pulmonary arterial hypertension (PAH), and blood biomarkers have been developed
      which aim to monitor such treatment, and which correlate well with physiological
      parameters, symptoms and mortality. However, little is known regarding biomarkers
      collected using non-invasive methods such as exhaled breath condensate (EBC). EBC
      biomarkers show potential as a rapid, repeatable and easy method of sampling the
      pulmonary vasculature in severely ill patients. The current study aimed to
      investigate EBC biomarkers in patients with PAH of different aetiologies. We
      studied 89 patients in four groups: pulmonary arterial hypertension (PAH, n =
      30), PAH associated with COPD (COPD/PAH, n = 14), COPD but no PAH (n = 16) and
      healthy controls (n = 29). Levels of the following EBC markers were measured:
      amino-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), 6
      keto prostaglandin (PG)F(1alpha), hydrogen peroxide (H(2)O(2)), total oxides of
      nitrogen (NO(x)), total protein and pH. ET-1 and NT-proBNP were measured in
      plasma concurrently. Data were analysed with ANOVA or Kruskal Wallis tests where
      appropriate. Correlations were performed using Pearson's correlation coefficient.
      NT-proBNP was detectable in EBC and was highest in the PAH group, significantly
      higher than the COPD/PAH group (194.1 +/- 23.3 versus 80.8 +/- 22.2 fmol ml(-1),
      p < 0.05). EBC ET-1 was significantly higher in subjects with PAH (1.53 +/- 0.32
      fmol ml(-1)) compared to those with COPD/PAH (0.25 +/- 0.03 fmol ml(-1), p <
      0.05) and controls (0.66 +/- 0.18 fmol ml(-1), p < 0.05). 6-keto PGF(1alpha) was
      low in the PAH group, significantly lower than the COPD/PAH group (4027 +/- 445
      versus 8381 +/- 1024 pg ml(-1), p < 0.01). EBC biomarkers are measurable in PAH.
      EBC ET-1 was raised in PAH compared with controls and patients with PAH secondary
      to COPD, whereas 6-keto PGF(1alpha) was low. EBC biomarkers may be useful in
      detection and monitoring of PAH.

PMID- 22854170
TI  - Tibial displacement and rotation during seated knee extension and wall squatting:
      a comparative study of tibiofemoral kinematics between chronic unilateral
      anterior cruciate ligament deficient and healthy knees.
AB  - BACKGROUND: Following anterior cruciate ligament (ACL) rupture, the knee becomes
      unstable with alterations in joint kinematics including anterior tibial
      displacement (ATD), and internal tibial rotation. Therapeutic exercises that
      promote faulty kinematics should be discouraged, especially early post
      reconstruction, to avoid graft stretching and possibly longer-term
      osteoarthritis. Our study aimed to compare ATD and tibial rotation during two
      commonly prescribed exercises, namely: open kinetic chain (OKC) seated extension
      and closed kinetic chain (CKC) single leg wall squatting in ACL-deficient and
      healthy knees. METHODS: Eight ACL-deficient patients and eight healthy subjects
      matched for age, gender and sports history were assessed using Qualisys 3D-Motion
      Analysis System to track 17 infrared markers while performing a seated knee
      extension with 3kg weight and a unilateral wall squat. We developed a model to
      measure joint kinematics through 70 degrees  of knee flexion and extension. ANOVA
      and paired t-tests compared relative ATD and tibial rotation between exercises
      and groups at 10 degrees  increments of flexion and extension. RESULTS: We found
      increased ATD in the wall squat compared to the seated extension (p=0.049). There
      was no difference in ATD between the healthy and ACL-deficient knees but overall
      the tibia was significantly more internally rotated (p=0.003) in ACL-deficient
      knees, irrespective of the exercise, possibly interfering with the screw-home
      mechanism. CONCLUSIONS: CKC exercises, in particular wall squats, are not
      necessarily safer for patients with ACL-deficiency and possibly ACL
      reconstruction; although generalization should only be made with appropriate
      caution. Clinicians require a detailed knowledge of the effect of exercise on
      knee joint kinematics.

PMID- 22854171
TI  - Purifying drinking water with sun, salt, and limes.

PMID- 22854172
TI  - U-series dating of speleothems from the Sierra del Endrinal (Grazalema Mountains,
      S Spain).
AB  - The uranium-series method is applied to date relic flowstone from karstic
      mountains in the south of Spain. Geomorphological mapping shows three staircased
      erosion surfaces with a typical karst landform. Exhumed flowstones fill the
      surficial palaeosinkholes and open fractures. Some of the samples analysed were
      impure carbonates consequently the leachate-leachate method was used to obtain
      activity ratios in the carbonate fraction. The ages obtained range from 34.4 ky
      to 266 ky and are grouped in four periods: 30-50 ky, 90-110 ky, 150 ky and 230
      270 ky. All these periods are related to the warm climate oxygen isotope stages 3
      and 5. Practically all locations present secular equilibrium in uranium isotopes.

PMID- 22854173
TI  - Investigation of gamma-ray shielding properties of concrete containing different
      percentages of lead.
AB  - In this work, concrete mixed with different percentages of lead is used to study
      gamma-ray shielding properties. The transmitted fluxes of gamma-rays that were
      emitted from (137)Cs and (60)Co sources were detected by a NaI(Tl) detector and
      analyzed by a MCA analyzer. Then, linear attenuation coefficients (LAC) and
      compressive strength of concrete specimens were experimentally investigated. By
      comparing the obtained data from concrete specimens with and without lead, it was
      observed that, if the powder of lead to cement ratio of 90% by weight is added in
      the concrete mixture, the concrete can be used as a suitable shield against gamma
      rays.

PMID- 22854174
TI  - Usage problems and social barriers faced by persons with a wheelchair and other
      aids. Qualitative study from the ergonomics perspective in persons disabled by
      rheumatoid arthritis and other conditions.
AB  - OBJECTIVE: The objective of this study was to identify the usage and
      accessibility problems faced by the disabled (whether in pain or not) users of
      assistive devices (conventional wheelchairs), identify physical barriers that
      limit their mobility, and recognize the socio-cultural practices excluding them
      from the design process of such devices. Another main purpose of this paper is to
      improve the ergonomic criteria that influence the design and manufacture of
      assistive devices. MATERIALS AND METHOD:  STUDY POPULATION: 15 patients with any
      of the following diagnoses: ankylosing spondylitis, rheumatoid arthritis, or
      amputees using wheelchairs in Mexico and Colombia. DESIGN: Qualitative study.
      Thematic analysis with a theoretical industrial design approach to employing
      usability testing for ergonomic analysis. RESULTS: We identified 6 issues
      associated with usability problems from the patient's standpoint: barriers for
      use of wheelchairs (usability and acceptability), creative adaptations, potential
      use of technical devices, independence, body perception and assistive devices,
      and architectural barriers. The ergonomic and usability requirements and the
      resulting level of independence vary across wheelchair users with chronic pain
      and those whose disability does not involve pain. The latter are more independent
      in their movements and decisions. CONCLUSIONS: User input is essential in the
      design of assistive devices. The proposal of "design from and for the user" must
      rely on both engineering and medical perspective on the ergonomy as well as the
      user interpretation of the environment and the experience of the disease. Thus we
      can arrive at a "user-centered design".

PMID- 22854175
TI  - A survey on the current evaluation and treatment of gout in Buenos Aires,
      Argentina.
AB  - OBJECTIVE: To evaluate the current management of gout in general practitioners
      and specialists in Buenos Aires city. MATERIAL AND METHODS: multiple choice,
      anonimous, survey, performed to 33 rheumatologists (REU), 52 Internal Medicine
      specialists (EMI) and 86 general practitioners (Otros). RESULTS: Gout is a very
      common or usual disease for 51.5% of REU vs 11.5% EMI and 8.1% Otros. At
      diagnosis, uric acid crystals are identified by 51.5% REU vs 28.8% EMI and 26.7%
      Otros and tophi observed by 60.6% REU vs 30.8% EMI and 30.2% Otros. REU and EMI
      should indicate colchicine for acute gout in 75.8% and 80.8% respectively vs 7.7%
      of Otros. REU measure patient's height/weight and waist circumference less
      frequently than EMI (66.7% vs 92.3% and 45.5% vs 75% respectively). CONCLUSIONS:
      REU usually examine patients with gout but in a chronic stage. The identification
      of crystals in synovial fluid is low. The use ofcolchicine is still high. REU
      should improve the evaluation of the metabolic syndrome.

PMID- 22854176
TI  - Patients with bipolar disorder show impaired performance on complex tests of
      social cognition.
AB  - The literature concerning social cognitive performance in people with bipolar
      disorder (BD) reveals a mixed pattern of findings. We compared performance
      between patients with BD and matched controls on two social cognitive tasks that
      involved: (i) the decoding of mental states from pictures of eyes (Reading the
      Mind in the Eyes Test), and (ii) a video-based test that requires participants to
      discriminate social cues to make interpersonal judgments (Interpersonal
      Perception Task-15; IPT-15). We also sought to evaluate the association between
      symptom severity, social functioning, and social cognitive ability in patients
      with BD. Relative to controls, patients with BD were impaired at discriminating
      mental states from pictures of eyes and in making complex social judgments.
      Impaired responding on the IPT-15 was also associated with reduced psychosocial
      functioning. These results provide evidence of impaired performance on complex
      tests of social cognition in patients with BD. Impairments in social cognition
      may be associated with well-documented declines in the frequency of social
      interactions and development of interpersonal relationships found in this patient
      population.

PMID- 22854177
TI  - HRS/ACCF expert consensus statement on pacemaker device and mode selection.

PMID- 22854178
TI  - Hospital volume responses to Medicare's Outpatient Prospective Payment System:
      evidence from Florida.
AB  - Effective in 2000, Medicare's Outpatient Prospective Payment System (OPPS) sets
      pre-determined reimbursement rates for hospital outpatient services, replacing
      the prior cost-based methods of reimbursement. Using Florida outpatient discharge
      data, we study the effect of OPPS on hospital outpatient volume. We find that on
      average Medicare rate cuts either decreased or had no significant effect on
      Medicare volume, but increased private fee-for-service (FFS) volume. We also find
      that responses vary with the hospital's "exposure" to Medicare payment changes,
      where exposure is measured as the baseline Medicare patient share. Compared to
      less exposed hospitals, highly exposed hospitals responded with larger increases
      in private FFS volume and with smaller decreases (in some cases, even increases)
      in Medicare volume when payment rates fell. Our results are consistent with
      provider demand inducement.

PMID- 22854179
TI  - The effect of simulated auditory hallucinations on daily activities in
      schizophrenia patients.
AB  - BACKGROUND: Auditory hallucinations often influence schizophrenia patients in
      many aspects. In order to develop effective behavioral interventions for
      overcoming enduring auditory hallucinations, it is necessary to understand how
      the annoying symptom affects the daily lives of the patients. This study
      evaluated the effect of hearing unusual voices on performing the activities of
      daily life in schizophrenia patients. METHODS: Eighteen hallucinating patients,
      18 nonhallucinating patients and 20 normal controls performed the virtual daily
      life task of packing 8 items for travel under 3 conditions: (1) without unusual
      voices and without avatars, (2) with unusual voices and without avatars and (3)
      with unusual voices and with avatars. Task completion time and the number of
      times the packing list was checked were recorded as a measure of the task
      performance. RESULTS: When exposed to unusual voices without avatars,
      hallucinating patients checked the packing list fewer times than nonhallucinating
      patients, and they required longer to complete the task, as positive and negative
      symptoms were worse. Subjective responses to unusual voices were stronger in
      hallucinating patients than in nonhallucinating patients. CONCLUSIONS: Daily-life
      activities of hallucinating patients may be less easily influenced by odd
      auditory stimuli in a nonsocial situation than those of nonhallucinating
      patients; however, hallucinating patients may feel more strongly affected by
      unusual voices. To better evaluate and thereby understand the difficulties faced
      by hallucinating patients in their daily life, the discrepancies between
      objective and subjective measures as well as social situations should be taken
      into consideration.

PMID- 22854181
TI  - Diminished photoinhibition is involved in high photosynthetic capacities in
      spring ephemeral Berteroa incana under strong light conditions.
AB  - Berteroa incana (B. incana), a spring ephemeral species of Brassicaceae,
      possesses very high photosynthetic capacities at high irradiances. Exploring the
      mechanism of the high light use efficiency of B. incana under strong light
      conditions may help to explore mechanisms of plants' survival strategies.
      Therefore, the photosynthetic characteristics of B. incana grown under three
      different light intensities (field conditions (field): 200-1500MUmolphotonsm(
      2)s(-1); greenhouse high light (HL) conditons: 600MUmolphotonsm(-2)s(-1); and
      greenhouse low light (LL) conditions: 100MUmolphotonsm(-2)s(-1)) were
      investigated and compared with those of the model plant Arabidopsis thaliana (A.
      thaliana). Our results revealed that B. incana behaved differently in adjusting
      its photosynthetic activities under both HL and LL conditions compared with what
      A. thaliana did under the same conditions, suggesting that the potential of
      photosynthetic capacity of B. incana might be enhanced under strong light
      conditions. Under LL conditions, B. incana reached its maximum photosynthetic
      activity at a much higher light intensity than A. thaliana did, although their
      maximum photochemical efficiency of photosystem II (PSII) (F(v)/F(m)) was almost
      the same. When grown under HL conditions, B. incana showed much higher
      photosynthetic capacity than A. thaliana. A detailed analysis of the OJIP
      transient kinetics of B. incana under HL and LL conditions revealed that HL-grown
      B. incana possessed not only a high ability in regulating photosystem
      stoichiometry that ensured high linear electron transport, but also an enhanced
      availability of oxidized plastoquinone (PQ) pool which reduced non-photochemical
      quenching (NPQ), especially its slow components qT and qI, and increased the
      photochemical efficiency, which in turn, increased the electron transport. We
      suggest that the high ability in regulating photosystem stoichiometry and the
      high level of the availability of oxidized PQ pool in B. incana under strong
      light conditions play important roles in its ability to retain higher
      photosynthetic capacity under extreme environmental conditions.

PMID- 22854180
TI  - Asg1 is a stress-inducible gene which increases stomatal resistance in salt
      stressed potato.
AB  - The identification of critical components in plant salt stress adaptation has
      greatly benefitted, in the last two decades, from fundamental discoveries in
      Arabidopsis and close model systems. Nevertheless, this approach has also
      highlighted a non-complete overlap between stress tolerance mechanisms in
      Arabidopsis and agricultural crops. Within a long-running research program aimed
      at identifying salt stress genetic determinants in potato by functional screening
      in Escherichia coli, we isolated Asg1, a stress-related gene with an unknown
      function. Asg1 is induced by salt stress in both potato and Arabidopsis and by
      abscisic acid in Arabidopsis. Asg1 is actively transcribed in all plant tissues.
      Furthermore, Asg1 promoter analysis confirmed its ubiquitous expression, which
      was remarkable in pollen, a plant tissue that undergoes drastic
      dehydration/hydration processes. Fusion of Asg1 with green fluorescent protein
      showed that the encoded protein is localized close to the plasma membrane with a
      non-continuous pattern of distribution. In addition, Arabidopsis knockout asg1
      mutants were insensitive to both NaCl and sugar hyperosmotic environments during
      seed germination. Transgenic potato plants over-expressing the Asg1 gene revealed
      a stomatal hypersensitivity to NaCl stress which, however, did not result in a
      significantly improved tuber yield in stress conditions. Altogether, these data
      suggest that Asg1 might interfere with components of the stress signaling pathway
      by promoting stomatal closure and participating in stress adaptation.

PMID- 22854183
TI  - Sequence analysis and gene expression of putative exo- and endo-glucanases from
      oil palm (Elaeis guineensis) during fungal infection.
AB  - Glucanases are enzymes that hydrolyze a variety beta-d-glucosidic linkages. Plant
      beta-1,3-glucanases are able to degrade fungal cell walls; and promote the
      release of cell-wall derived fungal elicitors. In this study, three full-length
      cDNA sequences encoding oil palm (Elaeis guineensis) glucanases were analyzed.
      Sequence analyses of the cDNA sequences suggested that EgGlc1-1 is a putative
      beta-d-glucan exohydolase belonging to glycosyl hydrolase (GH) family 3 while
      EgGlc5-1 and EgGlc5-2 are putative glucan endo-1,3-beta-glucosidases belonging to
      GH family 17. The transcript abundance of these genes in the roots and leaves of
      oil palm seedlings treated with Ganoderma boninense and Trichoderma harzianum was
      profiled to investigate the involvement of these glucanases in oil palm during
      fungal infection. The gene expression of EgGlc1-1 in the root of oil palm
      seedlings was increased by T. harzianum but suppressed by G. boninense; while the
      gene expression of both EgGlc5-1 and EgGlc5-2 in the roots of oil palm seedlings
      was suppressed by G. boninense or/and T. harzianum.

PMID- 22854182
TI  - Hormonal regulation of leaf senescence in Lilium.
AB  - In addition to floral senescence and longevity, the control of leaf senescence is
      a major factor determining the quality of several cut flowers, including Lilium,
      in the commercial market. To better understand the physiological process
      underlying leaf senescence in this species, we evaluated: (i) endogenous
      variation in the levels of phytohormones during leaf senescence, (ii) the effects
      of leaf darkening in senescence and associated changes in phytohormones, and
      (iii) the effects of spray applications of abscisic acid (ABA) and pyrabactin on
      leaf senescence. Results showed that while gibberellin 4 (GA(4)) and salicylic
      acid (SA) contents decreased, that of ABA increased during the progression of
      leaf senescence. However, dark-induced senescence increased ABA levels, but did
      not affect GA(4) and SA levels, which appeared to correlate more with changes in
      air temperature and/or photoperiod than with the induction of leaf senescence.
      Furthermore, spray applications of pyrabactin delayed the progression of leaf
      senescence in cut flowers. Thus, we conclude that (i) ABA plays a major role in
      the regulation of leaf senescence in Lilium, (ii) darkness promotes leaf
      senescence and increases ABA levels, and (iii) exogenous applications of
      pyrabactin inhibit leaf senescence in Lilium, therefore suggesting that it acts
      as an antagonist of ABA in senescing leaves of cut lily flowers.

PMID- 22854184
TI  - The synthesis of 2-deoxy-alpha-D-glycosides from D-glycals catalyzed by TMSI and
      PPh3.
AB  - 2-Deoxyglycosides were synthesized in high alpha-selectivity by the direct
      addition of alcohols to D-glucal and D-galactal catalyzed by TMSI and PPh(3). The
      acid labile isopropylidene group is tolerated under this condition.

PMID- 22854185
TI  - Data interpretation in breath biomarker research: pitfalls and directions.
AB  - Most--if not all--potential diagnostic applications in breath research involve
      different marker concentrations rather than unique breath markers which only
      occur in the diseased state. Hence, data interpretation is a crucial step in
      breath analysis. To avoid artificial significance in breath testing every effort
      should be made to implement method validation, data cross-testing and statistical
      validation along this process. The most common data analysis related problems can
      be classified into three groups: confounding variables (CVs), which have a real
      correlation with both the diseased state and a breath marker but lead to the
      erroneous conclusion that disease and breath are in a causal relationship; voodoo
      correlations (VCs), which can be understood as statistically true correlations
      that arise coincidentally in the vast number of measured variables; and
      statistical misconceptions in the study design (SMSD). CV: Typical confounding
      variables are environmental and medical history, host factors such as gender,
      age, weight, etc and parameters that could affect the quality of breath data such
      as subject breathing mode, effects of breath sampling and effects of the
      analytical technique itself. VC: The number of measured variables quickly
      overwhelms the number of samples that can feasibly be taken. As a consequence,
      the chances of finding coincidental 'voodoo' correlations grow proportionally.
      VCs can typically be expected in the following scenarios: insufficient number of
      patients, (too) many measurement variables, the use of advanced statistical data
      mining methods, and non-independent data for validation. SMSD: Non-prospective,
      non-blinded and non-randomized trials, a priori biased study populations or group
      selection with unrealistically high disease prevalence typically represent
      misconception of study design. In this paper important data interpretation issues
      are discussed, common pitfalls are addressed and directions for sound data
      processing and interpretation are proposed.

PMID- 22854186
TI  - Strategies for greener hospital operating rooms.

PMID- 22854187
TI  - Dietary protein intake and risk of stroke in women.
AB  - BACKGROUND: A high protein intake may reduce the risk of stroke but epidemiologic
      data on protein intake in relation to stroke risk are limited and inconsistent.
      Our objective was to test the hypothesis that protein intake would be inversely
      associated with risk of stroke. METHODS AND RESULTS: We conducted a population
      based prospective cohort study consisting of 34,670 Swedish women who were free
      of cardiovascular disease and cancer in 1997. Diet was assessed with a food
      frequency questionnaire. Incident cases of stroke were ascertained from the
      Swedish Hospital Discharge Registry. We estimated relative risks (RR) with 95%
      confidence intervals (CI) using Cox proportional hazard regression model. During
      10.4 years of follow-up, 1680 stroke events were identified, including 1310
      cerebral infarctions, 154 intracerebral hemorrhages, 79 subarachnoid hemorrhages,
      and 137 unspecified strokes. Intake of total and animal protein, but not
      vegetable protein, was statistically significantly inversely associated with risk
      of total stroke and cerebral infarction after adjustment for other risk factors
      for stroke. The multivariable RRs of total stroke for the highest versus lowest
      quintile of intake were 0.74 (95% CI: 0.61, 0.91; P for trend = 0.006) for total
      protein and 0.71 (95% CI: 0.57, 0.88; P for trend = 0.01) for animal protein. The
      associations were stronger in women with a history of hypertension (RR of total
      stroke = 0.56; 95% CI: 0.40, 0.78 for highest versus lowest quintile of total
      protein). CONCLUSION: These findings suggest that dietary protein intake is
      inversely associated with risk of stroke in women with hypertension.

PMID- 22854188
TI  - Carotid atherosclerosis and 10-year changes in cognitive function.
AB  - BACKGROUND: Carotid atherosclerosis has been suggested to be involved in
      cognitive decline. METHODS: The Epidemiology of Hearing Loss Study is a
      longitudinal study of aging among Beaver Dam residents, WI. In 1998-2000, carotid
      intima-media thickness (IMT) and plaque were measured by ultrasound; cognitive
      function was measured by the Mini-Mental State Examination (MMSE). Follow-up
      examinations were conducted in 2003-2005 and 2009-2010. Incidence of cognitive
      impairment was defined as an MMSE score <24 or reported physician-diagnosed
      dementia during the follow-up. In the last examination, five additional cognitive
      tests were added. The associations of carotid atherosclerosis with incident
      cognitive impairment and cognitive test performance ten years later were
      evaluated. RESULTS: A total of 1651 participants (mean age 66.8 years, 41% men)
      without cognitive impairment at baseline were included in the incidence analysis.
      IMT was associated with incidence of cognitive impairment after multiple
      adjustments (hazard ratio: 1.09, p = 0.02 for each 0.1 mm increase in IMT). A
      total of 1311 participants with atherosclerosis data at baseline had the
      additional cognitive tests 10 years later. Larger IMT was associated with longer
      time to complete the Trail-Making Test-part B after multiple adjustments (0.1 mm
      IMT: 2.3 s longer, p = 0.02). Plaque was not associated with incident cognitive
      impairment or cognitive test performance 10 years later. CONCLUSIONS: In this
      population-based longitudinal study, carotid IMT was associated with a higher
      risk of developing cognitive impairment during the 10-year follow-up, and was
      associated with poorer performance in a test of executive function 10 years
      later.

PMID- 22854190
TI  - Genetic correlations among facets of type A behavior and personality.
AB  - The purpose of this study was to examine the phenotypic, genetic, and
      environmental relationships between multiple dimensions of Type A behavior and
      personality. Adult twins (N=247 pairs) completed a self-report personality
      measure and a work style questionnaire that measured six facets of Type A
      behavior: impatience, anger, work involvement, time urgency, job dissatisfaction,
      and competitiveness. Univariate results suggest that only the job dissatisfaction
      facet of Type A behavior was explained by non-genetic (environmental) factors.
      Multivariate results suggest that all of the genetically determined facets of
      Type A behavior show some correspondence with at least one of the personality
      factors found in the study, suggesting that some of the phenotypic (observed)
      relationships could be due to common genetic factors.

PMID- 22854189
TI  - Examining the overlap between bipolar disorder, nonaffective psychosis, and
      common mental disorders using latent class analysis.
AB  - BACKGROUND: While dimensional models of psychopathology have delineated two broad
      factors underlying common mental disorders--internalizing and externalizing--it
      is unclear where bipolar disorder and nonaffective psychoses fit in relation to
      this structure and to each other. Given their low prevalence rates in the general
      population, these disorders generally tend to be excluded from such models. The
      current study used the person-centered approach of latent class analysis (LCA) to
      evaluate this question. SAMPLING AND METHODS: LCA of diagnostic data from an
      epidemiological sample, the National Comorbidity Survey (n = 5,877), was
      undertaken. Diagnoses utilized in analyses included mania, nonaffective
      psychoses, specific phobia, social phobia, agoraphobia, panic disorder, major
      depression, dysthymia, generalized anxiety disorder, post-traumatic stress
      disorder, alcohol dependence, drug dependence, and conduct disorder. RESULTS:
      Results indicated that a 5-class LCA model optimally fit the data. Four of the
      classes mirrored those found in dimensional models--a class with few disorders,
      and 3 others with primarily fear, distress, and externalizing disorders. However,
      the fifth class--which is not evident in dimensional models--was unique in that
      it was the only one in which individuals demonstrated significant probabilities
      of both manic episodes and nonaffective psychoses in addition to markedly high
      levels of internalizing and externalizing disorders. CONCLUSION: This finding has
      important implications for nosological classification of psychopathology.

PMID- 22854191
TI  - Real-time detection of epileptic seizures in animal models using reservoir
      computing.
AB  - In recent years, an increasing number of studies have investigated the effects of
      closed-loop anti-epileptic treatments. Most of the current research still is very
      labour intensive: real-time treatment is manually triggered and conclusions can
      only be drawn after multiple days of manual review and annotation of the
      electroencephalogram (EEG). In this paper we propose a technique based on
      reservoir computing (RC) to automatically and in real-time detect epileptic
      seizures in the intra-cranial EEG (iEEG) of epileptic rats in order to
      immediately trigger seizure treatment. The performance of the system is evaluated
      in two different seizure types: absence seizures from genetic absence epilepsy
      rats from Strasbourg (GAERS) and limbic seizures from post status epilepticus
      (PSE) rats. The dataset consists of 452 hours iEEG from 23 GAERS and 2083 hours
      iEEG from 22 PSE rats. In the default set-up the system detects 0.09 and 0.13
      false positives per seizure and misses 0.07 and 0.005 events per seizure for
      GAERS and PSE rats respectively. It achieves an average detection delay below 1s
      in GAERS and less than 10s in the PSE data. This detection delay and the number
      of missed seizures can be further decreased when a higher false positive rate is
      allowed. Our method outperforms state-of-the-art detection techniques and only a
      few parameters require optimization on a limited training set. It is therefore
      suited for automatic seizure detection based on iEEG and may serve as a useful
      tool for epilepsy researchers. The technique avoids the time-consuming manual
      review and annotation of EEG and can be incorporated in a closed-loop treatment
      strategy.

PMID- 22854192
TI  - Diagnostic efficiency of the German version of the Standardized Assessment of
      Personality--Abbreviated Scale.
AB  - BACKGROUND: About 30% of outpatients meet the criteria of a personality disorder
      (PD). When PD remains unnoticed or untreated, individuals with co-occurring PD
      benefit considerably less from disorder-related treatments for axis I disorders
      than patients without PD. The present study examines the diagnostic efficiency of
      the German version of the Standardized Assessment of Personality--Abbreviated
      Scale Self-Rating Version (SAPAS-SR). SAMPLING AND METHODS: Based on the signal
      detection theory, receiver operating characteristics as well as reliability and
      validity indicators are determined in a heterogeneous outpatient sample (n =
      230). RESULTS: The values of internal consistency and the validity indicators
      turned out to be in the expected range. The area under the curve was low, at
      0.67. Using the cutoff point of 4, sensitivity (80%) and specificity (46%) values
      were at a level that was only acceptable. CONCLUSIONS: Since specificity was
      lower than in previous studies, using the SAPAS-SR results in a moderate cost
      efficiency only.

PMID- 22854193
TI  - Suppression of autoimmune arthritis by Celastrus-derived Celastrol through
      modulation of pro-inflammatory chemokines.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
      inflammation of the synovial joints, deformities, and disability. The prolonged
      use of conventional anti-inflammatory drugs is associated with severe adverse
      effects. Therefore, there is an urgent need for safer and less expensive
      therapeutic products. Celastrol is a bioactive component of Celastrus, a
      traditional Chinese medicine, and it possesses anti-arthritic activity. However,
      the mechanism of action of Celastrol remains to be fully defined. In this study
      based on the rat adjuvant-induced arthritis (AA) model of RA, we examined the
      effect of Celastrol on two of the key mediators of arthritic inflammation, namely
      chemokines and their receptors, and related pro-inflammatory cytokines. We
      treated arthritic Lewis rats with Celastrol (200MUg/rat) or its vehicle by daily
      intraperitoneal (ip) injection beginning at the onset of AA. At the peak phase of
      AA, the sera, the draining lymph node cells, spleen adherent cells, and synovial
      infiltrating cells of these rats were harvested and tested. Celastrol-treated
      rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1,
      MIP-1alpha, and GRO/KC) as well as cytokines (TNF-alpha and IL-1beta) that induce
      them, compared to the vehicle-treated rats. However, Celastrol did not have much
      effect on cellular expression of chemokine receptors except for an increase in
      CCR1. Further, Celastrol inhibited the migration of spleen adherent cells in
      vitro. Thus, Celastrol-induced suppression of various chemokines that mediate
      cellular infiltration into the joints might contribute to its anti-arthritic
      activity. Our results suggest that Celastrol might offer a promising
      alternative/adjunct treatment for RA.

PMID- 22854194
TI  - Synthesis and evaluation of small libraries of triazolylmethoxy chalcones,
      flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG.
AB  - A synthetic strategy to access small libraries of triazolylmethoxy chalcones 4{1
      20}, triazolylmethoxy flavanones 5{1-10} and triazolylmethoxy aminopyrimidines
      6{1-17} from a common substrate 4-propargyloxy-2-hydroxy acetophenone using a set
      of different reactions has been developed. The chalcones and flavanones were
      screened against mycobacterial FAS-II pathway using a recombinant mycobacterial
      strain, against which the most potent compound showed ~88% inhibition in
      bacterial growth and substantially induction of reporter gene activity at 100 MUM
      concentration. The triazolylmethoxy aminopyrimdines were screened against PknG of
      Mycobaceterium tuberculosis displaying moderate to good activity (23-53%
      inhibition at 100 MUM), comparable to the action of a standard inhibitor.

PMID- 22854196
TI  - Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on
      mitochondrial metabolic energy conversion.
AB  - Obesity is quickly becoming an increasing problem in the developed world. One of
      the major fundamental causes of obesity and diabetes is mitochondria dysfunction
      due to faulty metabolic pathways which alter the metabolic substrate flux
      resulting in the development of these diseases. This paper examines the role of
      mitochondrial carbonic anhydrase (CA) isozymes in the metabolism of pyruvate,
      acetate, and succinate when specific isozyme inhibitors are present. Using a
      sensitive electrochemical approach of wired mitochondria to analytically measure
      metabolic energy conversion, we determine the resulting metabolic difference
      after addition of an inhibitory compound. We found that certain sulfonamide
      analogues displayed broad spectrum inhibition of metabolism, where others only
      had significant effect on some metabolic pathways. Pyruvate metabolism always
      displayed the most dramatically affected metabolism by the sulfonamides followed
      by fatty acid metabolism, and then finally succinate metabolism. This allows for
      the possibility of using designed sulfonamide analogues to target specific
      mitochondrial CA isozymes in order to subtly shift metabolism and glucogenesis
      flux to treat obesity and diabetes.

PMID- 22854195
TI  - Transition state analogue inhibitors of human methylthioadenosine phosphorylase
      and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase
      incorporating acyclic ribooxacarbenium ion mimics.
AB  - Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and
      coupled via a methylene link to 9-deazaadenine. The products were tested for
      inhibition against human MTAP and Escherichia coli and Neisseria meningitidis
      MTANs and gave K(i) values as low as 0.23 nM. These results were compared to
      those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)
      1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1
      [9-deazaadenin-9-yl)methyl]3-hydroxy-4-methylthiomethylpyrrolidine (MT-DADMe
      Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of
      approximately 2- to 4-fold those of 3 but were significantly weaker than 4.
      Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic
      product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another
      case, N-methylation of a side chain secondary amine resulted in a 250-fold loss
      of activity against the same enzyme [(+/-)-65 vs (+/-)-68]. The inhibition
      results were also contrasted with those acyclic derivatives previously prepared
      as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where
      some inhibitors in the latter case were found to be more potent than their cyclic
      counterparts.

PMID- 22854197
TI  - Plasmacytoid variant of urothelial carcinoma: a report of a rare case.
AB  - Plasmacytoid variant of urothelial bladder carcinoma is rare. We report a case
      with a detailed discussion of features that help characterize this variant. A 50
      year-old man originally presented with gross hematuria. Resections at that time
      revealed a grade I-II superficial urothelial carcinoma. He did not return for
      follow-up until recently, three years later, when he presented with recurrent
      gross hematuria. An extensive tumor was identified on cystoscopy. Resection
      revealed a high-grade non-invasive papillary urothelial carcinoma. CT scan
      revealed a large urinary bladder solid mass with bilateral hydronephrosis.
      Metastatic workup was negative. The patient underwent a radical cystectomy with
      creation of ileal conduit. Final pathology revealed plasmacytoid variant of
      urothelial carcinoma with extensive vascular invasion and extension to the
      perivesical adipose tissue. We present a rare variant of urothelial carcinoma
      with comprehensive analysis of the morphological and immunophenotypic clues that
      characterize this variant.

PMID- 22854198
TI  - Noncompaction myocardium in association with type Ib glycogen storage disease.
AB  - Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the
      compaction process during the normal development of the heart. Left ventricular
      noncompaction has been reported to be associated with a variety of cardiac and
      extracardiac, especially neuromuscular abnormalities. Moreover, it has been
      suggested that metabolic alterations could be responsible for the noncompaction.
      However, no association of noncompaction myocardium with type Ib glycogen storage
      disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a
      transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a
      markedly enlarged liver and, additionally, in neutropenia, recurrent infections,
      and inflammatory bowel disease. Until now, no muscular or cardiac involvement has
      been described in type Ib GSD patients. The present case represents the first
      report of a noncompaction myocardium in a child with type Ib GSD who died of
      sudden clinical deterioration at the age of four.

PMID- 22854199
TI  - Order and randomness in Kolmogorov-Johnson-Mehl-Avrami-type phase transitions.
AB  - The distribution of points on a 2D domain influences the kinetics of its coverage
      when a growth law is attached at each point. This implies that the kinetics of
      space filling can be adopted as a descriptor of the degree of order of the
      initial point distribution. In this paper, the degree of order of an initial
      array of points has been changed following two paths: (i) from a regular square
      lattice, through increasing displacement assigned to each point, towards
      Poissonian disorder; (ii) from a Poissonian distribution, by introducing a hard
      core potential with increasing correlation lengths, towards a more ordered
      lattice. A linear growth law has been attached to the points of the initial array
      and the kinetics X(X(e)), where X(e) is the extended coverage as defined in the
      Kolmogorov-Johnson-Mehl-Avrami model, has been monitored. The quantitative
      analysis has been performed by fitting the kinetics to an equation which we
      propose for the first time and which has proved to be, in fact, highly suitable
      for the purpose. The results demonstrate that the gross of variation from order
      to disorder is obtained for point displacements, u, of the order of a, the latter
      being the constant of a square lattice. Vice versa, the introduction of a
      correlation distance in a random distribution provokes at most an order limited
      to the first neighbors and no real order can ever be reached. Others descriptors
      have been investigated, all confirming our results. We also developed an
      analytical description based on the use of the f-functions, as have been defined
      by Van Kampen, up to the second order terms. Such a description has been shown to
      work well for u/a < 1 within an interval DeltaX(e) which depends on the epsilon
      value.

PMID- 22854200
TI  - The Influence of receptor kinetics on the onset and duration of action and the
      therapeutic index of NVA237 and tiotropium.
AB  - Studies under nonphysiological conditions suggest that long receptor residency
      time is responsible for the 24-h duration of action of the long-acting muscarinic
      antagonist (LAMA) tiotropium. Our aim was to determine how clinically relevant
      dissociation rates under more physiological conditions influence the differences
      in onset of action between tiotropium and 3-[(cyclopentylhydroxyphenylacetyl oxy]
      1,1-dimethyl-pyrrolidinium bromide (NVA237), a once-daily dry-powder formulation
      of the LAMA glycopyrronium bromide in development for chronic obstructive
      pulmonary disease. In addition, we have investigated kinetic selectivity at each
      of the muscarinic receptor subtypes to determine whether the improved
      cardiovascular therapeutic index obtained with NVA237 in animal models is
      attributable to differences in kinetic rate constants. The binding of radioligand
      [3H]N-methyl-scopolamine was measured in the presence/absence of several
      concentrations of unlabeled competitors, and data were analyzed using a
      competition kinetic model to provide on/off rates for the competitor. We found
      shorter dissociation half-lives for NVA237 and tiotropium under physiological
      (11.4 and 46.2 min, respectively) versus nonphysiological conditions (173 and 462
      min, respectively). NVA237 had a more rapid onset of action (3-4.8 times) versus
      tiotropium, determined in an vitro calcium and rat tracheal strip assay.
      Simulations suggested that the more rapid onset of NVA237 action could be
      explained by differences in kinetic parameters. NVA237 had greater equilibrium
      binding and kinetic selectivity for muscarinic type 3 (M3) versus muscarinic type
      2 (M2) receptors, with a faster off rate from M2 versus M3 receptors than
      tiotropium, potentially affording it a more favorable therapeutic index. This
      study suggests that the 24-h duration of action of NVA237 and tiotropium is not
      solely the result of their slow dissociation from the M3 receptor and highlights
      the importance of conducting in vitro experiments in conditions reflecting those
      in vivo.

PMID- 22854201
TI  - Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal
      lesions by antisecretory drugs in rats: the role of intestinal motility.
AB  - Antisecretory drugs such as histamine H2-receptor antagonists (H2-RAs) and proton
      pump inhibitors (PPIs) are commonly used for the treatment of gastric and
      duodenal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs).
      However, the effects of these drugs on NSAID-induced small intestinal ulcers are
      not fully understood. The effects of H2-RAs and PPIs on NSAID-induced
      gastrointestinal lesions and small intestinal motility were examined in rats.
      Male Wistar rats (180-220 g) were used. Indomethacin (10 mg/kg) was administered
      orally in fasted or fed rats, and gastrointestinal lesions were examined 24 h
      after indomethacin administration. Intestinal motility was measured by using a
      balloon method under urethane anesthesia. Indomethacin produced multiple lesions
      in the gastric corpus in fasted rats and in the small intestine in fed rats: 1)
      H2-RAs (cimetidine, ranitidine, and famotidine) and PPIs (omeprazole,
      lansoprazole, and rabeprazole) markedly inhibited the formation of gastric
      lesions. 2) The drugs, except for lansoprazole, increased intestinal lesions. 3)
      H2-RAs augmented the increase in intestinal motility caused by indomethacin, and
      the effects of H2-RAs on motility and intestinal lesions were markedly inhibited
      by atropine. 4) Lansoprazole inhibited the formation of intestinal lesions, and
      the effect was prevented by both pharmacological ablation of capsaicin-sensitive
      sensory neurons and pretreatment with N-nitro-l-arginine methyl ester, a
      selective inhibitor of nitric-oxide synthesis. The results suggest that: 1)
      inhibition of acid secretion by antisecretory drugs may exacerbate NSAID-induced
      intestinal lesions, 2) H2-RAs further aggravate lesions by increasing intestinal
      motility via the activation of cholinergic pathways, and 3) lansoprazole protects
      the intestinal mucosa against NSAID-related ulcerative stimuli.

PMID- 22854202
TI  - Transcriptional profiling of inflammatory cytokine genes in African buffaloes
      (Syncerus caffer) infected with Theileria parva.
AB  - Theileria parva (T. parva) causes East Coast fever (ECF), which is of huge
      economic importance to Eastern and Southern African countries. In a previous
      bovine model, inflammatory cytokines were closely associated with disease
      progression in animals experimentally infected with T. parva. The African Cape
      buffalo (Syncerus caffer), the natural reservoir for T. parva, is completely
      resistant to ECF despite a persistently high parasitaemia following infection
      with T. parva. Characterizing basic immunological interactions in the host is
      critical to understanding the mechanism underlying disease resistance in the
      African Cape buffalo. In this study, the expression level of several cytokines
      was analyzed in T. parva-infected buffaloes. There were no significant
      differences in the expression profiles of inflammatory cytokines between the
      infected and uninfected animals despite a remarkably high parasitaemia in the
      former. However, the expression level of IL-10 was significantly upregulated in
      the infected animals. These results indicate a correlation between diminished
      inflammatory cytokines response and disease resistance in the buffalo.

PMID- 22854204
TI  - [Rectal prolapse repair using transanal endoscopic surgery].
AB  - Rectal prolapse repair techniques using laparoscopic abdominal surgery are the
      treatments of choice. However, in patients with increased morbidity, perineal
      surgical techniques are indicated. Transanal endoscopic surgery is presented as a
      possible alternative option in groups with increased experience in it.

PMID- 22854205
TI  - [Indications and results of pancreatic metastasis resection. Experience in the
      Hospital Universitario de Bellvitge].
AB  - OBJECTIVE: To analyse the indications and results of pancreatic metastasis
      resection in a university hospital. PATIENTS AND METHODS: An analysis was
      performed on a prospective database from 1990 to 2010. The clinical-pathological
      and perioperative details, as well the follow-up results were analysed. RESULTS:
      Of the 710 pancreatic resections performed, 7 cases (0.99%) were due to a
      metastasis in the pancreas. The mean age of the patients was 53.3 years (20-77
      years), and 5 were male and 2 were women. Five (70%) patients were asymptomatic.
      The origin of the metastasis was: colon (n=3), kidney (n=2), jejunum (n=1), and
      testicle (n=1). In 4 cases they were situated in the head, 2 in the tail, and one
      in the body. The metastases were metachronous in 4 (57%) patients and the disease
      free interval was 29 months (17-48). There were 3 cases (43%) of synchronous
      metastases, with a mean recurrence-free time of 14 months, and survival of 21.6
      months. This was lower than that of patients with metachronous metastases, which
      was 27.8 months and with a survival of 32 months, respectively. The overall
      disease free interval and survival was 21.85 months and 27.5 months,
      respectively. CONCLUSION: Resection of pancreatic metastases can extend survival
      in selected patients.

PMID- 22854206
TI  - A general three-dimensional parametric geometry of the native aortic valve and
      root for biomechanical modeling.
AB  - The complex three-dimensional (3D) geometry of the native tricuspid aortic valve
      (AV) is represented by select parametric curves allowing for a general
      construction and representation of the 3D-AV structure including the cusps,
      commissures and sinuses. The proposed general mathematical description is
      performed by using three independent parametric curves, two for the cusp and one
      for the sinuses. These curves are used to generate different surfaces that form
      the structure of the AV. Additional dependent curves are also generated and
      utilized in this process, such as the joint curve between the cusps and the
      sinuses. The model's feasibility to generate patient-specific parametric geometry
      is examined against 3D-transesophageal echocardiogram (3D-TEE) measurements from
      a non-pathological AV. Computational finite-element (FE) mesh can then be easily
      constructed from these surfaces. Examples are given for constructing several 3D
      AV geometries by estimating the needed parameters from echocardiographic
      measurements. The average distance (error) between the calculated geometry and
      the 3D-TEE measurements was only 0.78+/-0.63mm. The proposed general 3D
      parametric method is very effective in quantitatively representing a wide range
      of native AV structures, with and without pathology. It can also facilitate a
      methodical quantitative investigation over the effect of pathology and mechanical
      loading on these major AV parameters.

PMID- 22854207
TI  - Helical flow in carotid bifurcation as surrogate marker of exposure to disturbed
      shear.
AB  - The main purpose of the study is to verify if helical flow might be a surrogate
      marker of the exposure to disturbed shear in normal carotid bifurcations. Based
      on hemodynamic simulations data of 50 carotid bifurcations, we defined
      appropriate helicity-based bulk flow descriptors and multivariate linear
      regression analysis was performed to assess the potential for a combination of
      helicity-based indicators in describing the exposure to disturbed shear. To
      select the optimal combination of helicity-based descriptors in the regression
      model, the Akaike information criterion was applied. The identified statistical
      model is composed of two bulk flow descriptors proposed here to quantify helicity
      intensity and the balance between counter-rotating helical flow patterns in the
      flow field. The model revealed the existence of a significant relationship with
      adjusted squared Pearson's correlation coefficient in the range 0.4-0.7
      (P<0.0001). In detail, while a high helicity intensity is instrumental in
      suppressing flow disturbances, this protective effect could be moderated when one
      direction of rotation is dominant in the flow field. The in vivo quantification
      of the bulk flow features emerging in this study would offer a practical way to
      infer the presence of disturbed shear in large-scale in vivo studies of local
      risk factors in atherosclerosis.

PMID- 22854208
TI  - Validity of lamellar body count as a fetal lung maturity assessment in twin
      pregnancy.
AB  - Fetal lung maturity assessment in twin pregnancy has been discussed, but is still
      controversial. The purpose of this study is to predict the occurrence of
      respiratory distress syndrome (RDS) using lamellar body count (LBC) and analyze
      the validity of LBC for fetal lung maturity assessment in twin pregnancy. Three
      hundred two amniotic fluid samples were obtained at cesarean section from 29 to
      38 weeks of gestation. Samples were analyzed immediately with no centrifugation
      and the number of lamellar bodies was counted using a platelet channel on the
      Sysmex SF-3000. There were 18 neonates (6.0%) suffering from RDS. An LBC cut-off
      value of 2.95*104/MUL resulted in 91.5% sensitivity and 83.3% specificity for
      predicting RDS. This cut-off value for predicting RDS was the same as that in
      singleton pregnancy. Moreover, the median LBC value in RDS cases was
      significantly lower than in non-RDS cases (1.50+/-1.1*104/MUL vs. 10.6+/
      7.5*104/MUL; p<.001). This is the first report on the validity of LBC in twin
      pregnancy and also the largest study on fetal lung maturity assessment in twin
      pregnancy. An LBC value of >2.95*104/MUL means reassuring findings for RDS even
      in twin pregnancy. We believe the data in this study provide valuable, new
      information for the management of twin pregnancies.

PMID- 22854209
TI  - Blink reflex in patients with postparalytic facial syndrome and blepharospasm:
      trigeminal and auditory stimulation.
AB  - OBJECTIVE: The enhancement of blink reflex (BR) excitability was shown in
      patients with postparalytic facial syndrome (PFS) and essential blepharospasm
      (EB). We prospectively investigated patients with PFS and EB whether BR
      alterations demonstrated by trigeminal stimulation will similarly be observed
      upon auditory stimulation. METHODS: Fifteen patients with PFS, 15 patients with
      EB, and 30 healthy volunteers were involved. Electrically stimulated trigeminal
      BR and auditory BR were studied bilaterally. RESULTS: The mean R2 amplitude and
      duration values were highest in EB patients, being significantly higher than PFS
      patients (p < 0.05) and control group (p < 0.01). The mean R2 duration in PFS
      patients were also significantly longer in compared to control group (p = 0.025).
      EB patients showed a higher mean R (auditory) amplitude and duration than PFS
      patients (p < 0.05) and controls (p < 0.04). The mean R (auditory) duration was
      longer on symptomatic side of PFS patients in compared to controls (p = 0.05).
      CONCLUSIONS: We observed that there is an enhanced excitability of BR circuit in
      postparalytic facial syndrome and essential blepharospasm, which could be evoked
      by auditory stimulation in addition to trigeminal stimulation. SIGNIFICANCE: The
      enhanced excitability in patients with EB and PFS probably originates from the
      final common pathway of BR circuit, namely facial motor or premotor neurons.

PMID- 22854210
TI  - The simple power of the probity probe.

PMID- 22854211
TI  - Employing an active mental task to enhance the performance of auditory attention
      based brain-computer interfaces.
AB  - OBJECTIVE: A majority of auditory brain-computer interfaces (BCIs) use the
      attentional modulation of auditory event-related potentials (ERPs) for
      communication and control. This study investigated whether the performance of an
      ERP-based auditory BCI can be further improved by increasing the mental efforts
      associated with the execution of the attention-related task. METHODS: Subjects
      mentally selected a target among a random sequence of spoken digits. Upon the
      detection of the target digit, the subjects were required to perform an active
      mental task (AMT) - mentally discriminating the gender property of the target
      voice. The total number of presented digits was manipulated to investigate
      possible influences of the number of choices. The subjects also participated in
      two control experiments, in which they were asked to (1) press a button to report
      their discrimination results or (2) simply count the appearance of the target
      digit without performing the AMT. RESULTS: Two ERP components, that is, a
      negative shift around 200 ms (Nd) over the fronto-central area and a positive
      deflection during 500-600 ms (late positive component, LPC) over the central
      parietal area, were modulated by execution of the AMT. Compared to a counting
      task, the AMT resulted in paradigm-specific enhanced LPC responses. The latency
      of the LPC was significantly correlated with the behavioural reaction time,
      indicating that the LPC could originate from a response-related brain network
      similar to P3b. The AMT paradigm resulted in an increase of 4-6% in BCI
      classification accuracies, compared to a counting paradigm that was considered to
      represent the traditional auditory attention BCI paradigms (p < 0.05). In
      addition, the BCI classification accuracies were not significantly affected by
      the number of BCI choices in the AMT paradigm. CONCLUSIONS: (1) LPC was
      identified as the AMT-specific ERP component and (2) the performance of auditory
      BCIs can be improved from the human response side by introducing additional
      mental efforts when executing attention-related tasks. SIGNIFICANCE: The
      neurophysiological characteristics of the recently proposed auditory BCI paradigm
      using an AMT were explored. The results suggest the proposed paradigm as a
      candidate for improving the performance of auditory BCIs.

PMID- 22854212
TI  - Recessive dystrophic epidermolysis bullosa: identification of a novel COL7A1
      mutation of D44N.

PMID- 22854213
TI  - Fibril formation and toxicity of the non-amyloidogenic rat amylin peptide.
AB  - Full-length native rat amylin 1-37 has previously been widely shown to be unable
      to form fibrils and to lack the toxicity of the human amylin form leading to its
      use as a non-amyloidogenic control peptide. A recent study has suggested that rat
      amylin 1-37 forms amyloidogenic beta-sheet structures in the presence of the
      human amylin form and suggested that this property could promote toxicity. Using
      TEM analysis we show here fibril formation by synthetic rat amylin 1-37 and 8-37
      peptides when the lyophilized HPLC purified peptides are initially dissolved in
      20 mM Tris-HCl. Dissolution of synthetic rat amylin 1-37 and 8-37 peptides in
      H(2)O or phosphate buffered saline failed to produce fibrils. Addition of 20 mM
      Tris-HCl to synthetic rat amylin 1-37 and 8-37 peptides initially dissolved in
      H(2)O also failed to induce fibril formation. The rat amylin fibrils have a
      uniform structure and bind Congo red suggesting that they are amyloid fibrils.
      The rat amylin fibrils also bind catalase, which could be inhibited by Amyloid
      beta 31-35 and a catalase amyloid-beta binding domain-like peptide (R9). The rat
      amylin 1-37 and 8-37 fibrils are toxic in both human pancreatic islet and
      neuronal cell culture systems. The toxicity of rat amylin fibrils can be
      inhibited by an amylin receptor antagonist (AC187) and a caspase inhibitor (zVAD
      fmk) in a similar manner to previous observations for human amylin toxicity.
      Chemically induced rat amylin fibril formation of uniform structured fibrils
      provides a potentially novel anti-amyloid drug discovery tool.

PMID- 22854214
TI  - Compositional characterization of GaAs/GaAsSb nanowires by quantitative HAADF
      STEM.
AB  - The Sb concentration in axial GaAs(1-x)Sb(x) inserts of otherwise pure GaAs
      nanowires has been investigated with quantitative high-angle annular dark-field
      scanning transmission electron microscopy (HAADF-STEM). The Sb concentration was
      quantified by comparing the experimental image intensities normalized to the
      incident beam intensity with intensities simulated with a frozen lattice
      multislice approach. Including static atomic displacements in the simulations was
      found to be crucial for correct compositional analysis of GaAs(1-x)Sb(x). HAADF
      intensities of individual nanowires were analysed both across the nanowires,
      exploiting their hexagonal cross-sectional shape, and along the evenly thick
      central part of the nanowires. From the cross-sectional intensity profiles, a
      decrease in the Sb concentration towards the nanowire outer surfaces was found.
      The longitudinal intensity profiles revealed a gradual build-up of Sb in the
      insert. The decrease of the Sb concentration towards the upper interface was
      either gradual or abrupt, depending on the growth routine chosen. The
      compositional analysis with quantitative HAADF-STEM was verified by energy
      dispersive X-ray spectroscopy.

PMID- 22854215
TI  - Morphology of spermatozoa of Dissomphalus connubialis (Ashmead, 1893)
      (Hymenoptera: Bethylidae).
AB  - In this study, the morphology of spermatozoa of Bethylidae Dissomphalus
      connubialis (Pristocerinae) was analyzed using light and transmission electron
      microscopy. Spermatozoa of this species are thin, measure approximately 130 MUm
      in length and comprise a head region and flagellum region. The head is formed by
      the acrosome and nucleus. The acrosome consists of the acrosome vesicle and the
      perforatorium, the posterior portion of which is inserted into a cavity at the
      anterior extremity of the nucleus. The nucleus is compact, electron-dense and
      measures 15 MUm in length. The flagellum possesses two mitochondrial derivatives,
      two accessory bodies and one axoneme with a 9+9+2 microtubular pattern. The
      nucleus is connected to the flagellum by the centriole adjunct. Mitochondrial
      derivatives are compact, apparently without paracrystalline material and with
      rare mitochondrial cristae. They are asymmetric in length, such that the larger
      mitochondrial derivative begins parallel to the posterior region of the nucleus
      and the smaller mitochondrial derivative begins just below the centriole adjunct.
      The basic structure of spermatozoa of D. connubialis is similar to that of other
      Aculeata studied. However, this species shows characteristics not seen in other
      Hymenoptera, such as the wide electron-lucid region that separates the acrosomal
      vesicle from the perforatorium and the depth of the cavity in the anterior
      extremity of the nucleus, into which the base of the perforatorium is inserted.
      There are also characteristics that distinguish this species from Bethylidae
      Prorops nasuta, including the fact that one of the mitochondrial derivatives lies
      to parallel to the nucleus over a long distance, the small quantity of cristae,
      the absence of paracrystalline material in these organelles, and the fact that
      the accessory microtubules are the first to terminate in the final portion of the
      flagellum.

PMID- 22854217
TI  - Attempted suicide in immigrants from Turkey: a comparison with Swiss suicide
      attempters.
AB  - BACKGROUND/AIMS: Turkish migrants have been shown to have an increased rate of
      suicide attempts as compared to native local populations and also to people in
      Turkey. In this study we conducted in-depth interviews with patients regarding
      their reasons for the attempt. SUBJECTS AND METHODS: Seventy Turkish immigrants
      admitted to the emergency unit of the Basel University Hospital after a suicide
      attempt were interviewed. Seventy Swiss suicide attempters, matched for age and
      sex, served as a comparator (case-control study). RESULTS: Turkish immigrants
      showed high rates of suicide attempts. The gender ratio (women/men) was 2.2;
      38.6% of all Turkish suicide attempters were women aged between 15 and 25 years.
      Most patients mentioned problems in their partnerships as the main reason for the
      suicide attempt (63% of Swiss and 54% of Turkish patients); 14% of the Swiss but
      none of the Turkish suicide attempters named social isolation as a cause; 9% of
      the Turkish patients reported 'threat of loss/rejection of status as refugee' as
      the main reason. Immigrants used analgesics more often, whilst Swiss patients
      tended to favour benzodiazepines. CONCLUSIONS: Our study suggests that cultural
      and immigration-specific issues play a role in the suicidal behaviour of
      immigrants. Turkish women aged between 15 and 25 years seem to be at an
      especially high risk.

PMID- 22854216
TI  - Analysis of nanostructure of red blood cells membranes by space Fourier transform
      of AFM images.
AB  - Atomic force microscopy (AFM) allows a researcher to obtain images of red blood
      cells (RBC) and their membranes. Various effects on blood lead to surface
      alterations of cell membranes. Such alterations are estimated by a corrugation of
      membrane surface. This problem is complicated for statistical analysis because
      the membrane is the ensemble of structures with different sizes. In the present
      work we used the space Fourier transform to decompose the complex AFM image of
      the surface into three simpler ones. The parameters of spectral windows were
      selected according to the natural structures of RBC membranes. This method
      allowed us to obtain high resolution images for the corresponding spectral
      windows, to establish specificity of alterations from each effect, to estimate
      quantitatively the membrane nanostructures at different space scales and to
      compare their sizes statistically after actions of different agents. The blood
      intoxication was modeled by adding hemin, furosemide, chlorpromazine and zinc
      ions into blood, in vitro.

PMID- 22854218
TI  - Investigation of the nitrogen hyperfine coupling of the second stable radical in
      gamma-irradiated l-alanine crystals by 2D-HYSCORE spectroscopy.
AB  - The second stable radical, NH(3)(+)C()(CH(3))COO(-), R2, in the gamma-irradiated
      single crystal of l-alanine and its fully (15)N-enriched analogue were studied by
      an advanced pulsed EPR technique, 2D-HYSCORE (two-dimensional hyperfine sublevel
      correlation) spectroscopy at 200K. The nitrogen hyperfine coupling tensor of the
      R2 radical was determined from the HYSCORE data and provides new experimental
      data for improved characterization of the R2 radical in the crystal lattice. The
      results obtained complement the experimental proton data available for the R2
      radical and could lead to increased accuracy and reliability of EPR spectrum
      simulations.

PMID- 22854219
TI  - The association between pathological internet use and comorbid psychopathology: a
      systematic review.
AB  - BACKGROUND: Pathological Internet use (PIU) has been conceptualized as an impulse
      control disorder that shares characteristics with behavioral addiction. Research
      has indicated a potential link between PIU and psychopathology; however, the
      significance of the correlation remains ambiguous. The primary objective of this
      systematic review was to identify and evaluate studies performed on the
      correlation between PIU and comorbid psychopathology; the secondary aims were to
      map the geographical distribution of studies, present a current synthesis of the
      evidence, and assess the quality of available research. SAMPLING AND METHODS: An
      electronic literature search was conducted using the following databases:
      MEDLINE, PsycARTICLES, PsychINFO, Global Health, and Web of Science. PIU and
      known synonyms were included in the search. Data were extracted based on PIU and
      psychopathology, including depression, anxiety, symptoms of attention deficit and
      hyperactivity disorder (ADHD), obsessive-compulsive symptoms, social phobia and
      hostility/aggression. Effect sizes for the correlations observed were identified
      from either the respective publication or calculated using Cohen's d or R(2). The
      potential effect of publication bias was assessed using a funnel plot model and
      evaluated by Egger's test based on a linear regression. RESULTS: The majority of
      research was conducted in Asia and comprised cross-sectional designs. Only one
      prospective study was identified. Twenty articles met the preset inclusion and
      exclusion criteria; 75% reported significant correlations of PIU with depression,
      57% with anxiety, 100% with symptoms of ADHD, 60% with obsessive-compulsive
      symptoms, and 66% with hostility/aggression. No study reported associations
      between PIU and social phobia. The majority of studies reported a higher rate of
      PIU among males than females. The relative risks ranged from an OR of 1.02 to an
      OR of 11.66. The strongest correlations were observed between PIU and depression;
      the weakest was hostility/aggression. CONCLUSIONS: Depression and symptoms of
      ADHD appeared to have the most significant and consistent correlation with PIU.
      Associations were reported to be higher among males in all age groups.
      Limitations included heterogeneity in the definition and diagnosis of PIU. More
      studies with prospective designs in Western countries are critically needed.

PMID- 22854220
TI  - Anterior vaginal cyst mimicking a cystocele assessed by transperineal ultrasound.

PMID- 22854221
TI  - Public safety assessment of electromagnetic radiation exposure from mobile base
      stations.
AB  - Exposure of the general public to electromagnetic radiation originating from
      randomly selected GSM/WCDMA base stations in Riyadh, Kingdom of Saudi Arabia has
      been assessed in the context of the International Commission on Non-Ionising
      Radiation Protection (ICNIRP) guidelines. The purpose of the measurement was to
      record the maximum power density of signals to estimate possible worst case
      exposure at each measurement location. These power density measurements were
      carried out at 60 mobile base stations located in different regions of the city.
      For each of these sites, three sectors were operational, yielding a total of 180
      sectors. Two positions were identified per site with the greatest power density
      values. Exposures from these base stations were generally found to be in the
      range of 0.313 to 0.00000149% of the ICNIRP general public reference level, and
      the greatest exposure near any of the base stations was 21.96 mW m(-2) for a
      wideband measurement in the 75-3000 MHz frequency range. Analysis of the measured
      data reveals several trends for different mobile bands with respect to maximum
      exposure in those locations. Additionally, a simplified calculation method for
      the electromagnetic fields was used to compare calculated and the measured data.
      It was determined, on the basis of both results of the measurements and
      calculations carried out for these selected base stations, that members of the
      public would not be exposed to in excess of a small fraction of the ICNIRP
      guidelines at any of those sites. These are first such measurements to be made in
      the Middle East and provide assurance that exposures in this region of the world
      do not seem to be any greater than elsewhere.

PMID- 22854222
TI  - Diagnosis of body dysmorphic disorder.

PMID- 22854223
TI  - Polymerized phospholipid bilayers as permanent coatings for small amine
      separations using mixed aqueous/organic capillary zone electrophoresis.
AB  - Phospholipid bilayer (SPB) coatings have been used in capillary electrophoresis
      to reduce the nonspecific adsorption between the capillary wall and cationic
      analytes. This paper describes the use of the polymerizable lipid 1,2-bis(10,12
      tricosadiynoyl)-sn-glycero-3-phosphocholine (Diyne PC) as a permanent capillary
      coating. A supported phospholipid bilayer was formed on the capillary walls and
      polymerization was performed in situ using ultraviolet irradiation. The
      polymerization reaction was monitored by UV-visible absorbance spectroscopy and
      atomic force microscopy. The EOF of the polymerized Diyne PC coating was
      moderately suppressed (2.0*10(-4)cm(2)/Vs) compared to a non-polymerized Diyne PC
      bilayer (0.3*10(-4)cm(2)/Vs), but the stability was improved significantly.
      Separations of benzylamine, veratrylamine, phenylethylamine and tolyethylamine
      using a poly Diyne PC coated capillary yielded efficiency of 220,000-370,000
      plates/m and peak asymmetry factor 0.48-1.18. Specifically, the poly(Diyne PC)
      coating provided improved separation resolution in NACE due to the reduced
      surface adsorption.

PMID- 22854224
TI  - Antioxidant benzimidazole bind bovine serum albumin.
AB  - 1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole (MBMPB) was
      synthesized and characterized by (1)H NMR, (13)C NMR, Mass and IR spectral
      analysis. The mutual interaction of MBMPB with bovine serum albumin (BSA) was
      investigated using solution spectral studies. The binding distance has been
      calculated based on the theory of Forester's non-radiation energy transfer
      (FRET). The Stern-Volmer quenching constant (K(sv)) were calculated at different
      temperature. The binding site (n), apparent binding constant (K(A)) and
      corresponding thermodynamic parameters (DeltaG,DeltaH and DeltaS) were
      calculated. Antioxidant analyses such as DPPH radical scavenging analysis,
      Superoxide anion scavenging analysis and Hydroxyl radical scavenging analysis
      have been carried out for MBMPB and it shows potential antioxidant property due
      to the presence of electron releasing methoxy group.

PMID- 22854225
TI  - In vitro evaluation of combined hyperthermia and photodynamic effects using
      magnetoliposomes loaded with cucurbituril zinc phthalocyanine complex on
      melanoma.
AB  - The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded
      with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs)
      and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects
      while using melanoma cells (B16-F10) as model. The liposomal formulations were
      characterized by both average diameter and zeta potential. The vesicle average
      size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to
      0.230. The zeta potential was significantly positive with values between 48 and
      57 mV. The cell viability (CV) after PD and HT treatments was assessed by
      colorimetric MTT method. Melanoma cells were initially treated with the liposome
      formulation without light and magnetic field application, revealing cell
      viability not different from the control cells (p>0.05). Photodynamic and
      hyperthermia assays were also applied separately, demonstrating that PD is more
      effective than HT in reducing the CV of the neoplastic cells. Combined
      application of both PD and HT treatments was even more effective in reducing the
      CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic
      field activation the CV was about half than PD applied alone. Therefore, the use
      of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy
      (PDT) and magnetohyperthermia (MHT) application can be considered as a potential
      tool to treat malignant melanoma.

PMID- 22854226
TI  - Use of non-vitamin, non-mineral (NVNM) supplements by hospitalized internal
      medicine patients and doctor-patient communication.
AB  - OBJECTIVE: To study non-vitamin, non-mineral (NVNM) supplements use and
      disclosure of among hospitalized internal medicine patients. METHODS: A
      convenience sample of patients completed an interviewer-administered
      questionnaire examining use of and perceptions regarding NVNM supplements, and
      disclosure to medical personnel. RESULTS: 280 patients were interviewed (54%
      female), 15.4% reporting NVNM supplement use. This practice was more prevalent
      among female patients (p=0.045), more educated (p<0.001) and patients with more
      impaired quality-of-life, measured by the SF-12 tool (p<0.020). The most common
      factor influencing NVNM supplement use was a physician's recommendation. Most
      (74%) patients using NVNM supplements reported having disclosed this practice to
      community-based physicians, with only 23.7% disclosing to hospital staff. Six
      patients reported using supplements at the exclusion of conventional medication,
      with potentially serious implications. CONCLUSION: While the majority of patients
      using NVNM supplements are sharing this information with their primary-care
      physicians, there is little disclosure of this practice to hospital staff. This
      may be due to a perceived negative attitude of medical professionals to
      complementary medicine, and a lack of awareness by hospital staff regarding such
      practices. PRACTICE IMPLICATIONS: Hospital-based medical professionals need to be
      aware of the use of NVNM supplements and the resulting implications by their
      internal medicine patients.

PMID- 22854227
TI  - Option Grids: shared decision making made easier.
AB  - OBJECTIVE: To describe the exploratory use of short decision support tools for
      patients, called Option Grids. Option Grids are summary tables, using one side of
      paper to enable rapid comparisons of options, using questions that patients
      frequently ask (FAQs) and designed for face-to-face clinical encounters. To date,
      most evidence about 'patient decision aids' has been based on tools with high
      content levels, designed for patients to use independently, either before or
      after visits. METHODS: We studied the use of Option Grids in a quality
      improvement project, collecting field notes and conducting interviews with
      clinical teams. RESULTS: In the 'Making Good Decisions in Collaboration' (MAGIC)
      program, clinicians found that using Option Grids made it easier to explain the
      existence of options and reported a 'handover' effect, where patient involvement
      in decision making was enhanced. CONCLUSION: Option Grids made options more
      visible and clinicians found it easier to undertake shared decision making when
      these tools were available. Used in a collaborative way, they enhance patients'
      confidence and voice, increasing their involvement in collaborative dialogs.
      PRACTICE IMPLICATIONS: Further work to confirm these preliminary findings is
      required, to measure processes and to assess whether these tools have similar
      impact in other clinical settings.

PMID- 22854228
TI  - Maternal hemodynamics in normal pregnancies at 11-13 weeks' gestation.
AB  - OBJECTIVE: In women with established pre-eclampsia and gestational diabetes there
      is an increase in central aortic systolic blood pressure (SBP(Ao)), pulse wave
      velocity (PWV) and augmentation index (AIx), which are measures of arterial
      stiffness. The aim of this study was to establish normal ranges for PWV, AIx and
      SBP(Ao) at 11-13 weeks' gestation and to examine the maternal characteristics
      which affect these parameters. METHODS: This was a prospective study in singleton
      pregnancies at 11+0-13+6 weeks' gestation. Maternal history and characteristics
      were recorded and PWV, AIx and SBP(Ao) were measured. Multiple regression
      analysis was used to examine which of the maternal characteristics provided a
      significant contribution in the prediction of Alx-75, PWV and SBP(Ao). RESULTS:
      In normal pregnancies PWV, AIx-75 and SBP(Ao) were related to certain maternal
      characteristics, including increase with maternal age for AIx-75 and PWV,
      decrease with maternal height for AIx-75 and increase with maternal weight for
      PWV and SBP(Ao) and decrease for AIx (p < 0.0001). The median, 5th, 10th, 90th
      and 95th percentiles for AIx-75 MoM (multiple of the unaffected median), PWV MoM
      and SBP(Ao) MoM were 1.00, 0.72, 0.79, 1.34 and 1.48; 1.00, 0.77, 0.82, 1.24 and
      1.33; and 1.00, 0.86, 0.88, 1.15 and 1.20, respectively. CONCLUSIONS: This study
      provides normal ranges for PWV, AIx and SBP(Ao) at 11-13 weeks' gestation and
      defines the maternal characteristics which affect these vascular parameters.

PMID- 22854230
TI  - Prosthetic valve thrombosis: keeping the valve ticking!
AB  - Prosthetic valve thrombosis is a serious acute complication of mechanical
      valvular replacement, with significant mortality and morbidity. This case
      highlights the key diagnostic features and the role of thrombolysis in treatment.

PMID- 22854229
TI  - Role of adherens junction proteins in differential herpes simplex virus type 2
      infectivity in communication-competent and -deficient cell lines.
AB  - BACKGROUND: Gap junctional intercellular communication decreases with HSV-2
      infection. To determine the importance of functional gap junctions for
      infectivity, we compared HSV-2 growth in communication-competent and -deficient
      cell lines. METHODS: HSV-2 infectivity was tested in five cell lines: WB rat
      liver epithelial cells (communication-competent), WB-aB1 (communication
      deficient), WB-a/32-10 (communication-rescued), HeLa (communication-deficient),
      and Cx43-transfected HeLa (communication-rescued) cells. HSV-2 growth curves and
      indirect immunofluorescence labeling of viral and cell proteins were performed in
      wild-type and mutant WB cells. RESULTS: Although wild-type WB cells were highly
      permissive for HSV-2 infection, virus production was significantly attenuated in
      communication-deficient and -rescued mutant WB cells. HeLa exhibited no
      difference in infectivity between communication-competent and -deficient cell
      lines. Tight and adherens junction proteins, including zonula occludens-1 and
      nectin-1, were not different in the WB cell lines. However, E-cadherin levels
      were elevated and beta-catenin was found to co-localize with glycoprotein E, a
      viral glycoprotein associated with cell-to-cell spread, in the mutant WB cells.
      CONCLUSIONS: These results suggest that attenuated viral production in mutant WB
      cells is due to viral protein co-localization with adherens junction proteins
      rather than the loss or restoration of functional gap junctions.

PMID- 22854231
TI  - Skin lesion in a patient with Hirschsprung's disease complicated with short bowel
      syndrome: what is your diagnosis?

PMID- 22854232
TI  - Unusual case of hyponatraemia.
AB  - Hyponatraemia is the most common electrolyte abnormality, encountered in up to
      30% of inpatients. Inappropriate management can have serious implications for
      patients; including demyelinating disease, coma and death. We have used a case
      report to identify the common problems, and provide useful strategies in
      management for which these can be avoided. The aim was to provide a framework
      which clinicians can adopt, in order to improve clinical practice and provide
      optimum outcome for the patient.

PMID- 22854233
TI  - Graves' disease--familiar foe, unfamiliar face.
AB  - A 38-year-old man from a remote tribal area of South India presented with right
      heart failure. On evaluation, he was found to have untreated Graves' disease (GD)
      with atrial fibrillation and pulmonary hypertension. The left ventricular
      function was normal. Secondary causes for pulmonary hypertension were ruled out.
      He was treated with carbimazole and low-dose propranolol. Post 4 months medical
      therapy, his pulmonary hypertension completely reversed, thus establishing GD as
      a reversible cause of pulmonary hypertension and isolated right heart failure.

PMID- 22854234
TI  - Periapical actinomycosis.
AB  - Actinomycosis is a rare chronic infection caused by species of Actinomyces and
      characterised by abscess formation, tissue fibrosis, suppurative lesions and
      fistulas with purulent discharge containing sulphur granules. Owing to its
      multiform manners of presentation and non-specificity from its clinical features,
      it has been considered as a challenging diagnosis. Periapical actinomycosis is
      one of the rarest forms of actinomycosis occurring in the maxillofacial region.
      In its occurrence it presents in the form of persistent and recurrent draining
      fistula in the periapical region. We report a case of periapical actinomycosis
      occurred in endodontically treated teeth and accidentally found to be
      actinomycosis during histopatological examination. An insight towards the portal
      of entry of the organisms into the periapical region is also discussed. The
      practice of sending even a tiny bit of tissues to histopathology obtained from
      periapical surgery will very well demonstrate this disease and help in rapid
      resolution through appropriate antibiotic therapy.

PMID- 22854235
TI  - Acute small bowel obstruction due to intussusception of malignant amelonatic
      melanoma of the small intestine.
AB  - Malignant melanoma is a common malignancy and cutaneous melanoma showed an
      unusual prediction to metastasise into the small intestine. At autopsy metastatic
      deposits found in 50-60%, but less than 2-4% of melanoma patients diagnosed to
      have gastrointestinal (GI) metastasis during the disease course and 4-9% GI
      melanoma had unknown primary melanoma, which should be considered metastatic
      because primary lesion may be very small to diagnose or had regressed
      spontaneously. Few cases reported to have intussusception as a presenting
      feature. We report a case of amelanotic metastatic melanoma presented with
      intussusception and without known primary melanoma. The patient presented with
      abdominal pain, vomiting and distension. He was diagnosed as having acute
      intestinal obstruction as confirmed by erect abdominal x-ray. Ultrasonography
      showed small intestine intussusception. Emergency laparotomy revealed ilieo-ileal
      type intussusception with intraluminal mass, which was resected and end-to-end
      anastomosis of bowel was performed. Histopathological and immunohistochemical
      examination of the resected specimen showed amelanotic melanoma.

PMID- 22854236
TI  - Development of Graves' disease after long-standing hypothyroidism on treatment,
      with acute toxicity to thionamides and lithium.
AB  - Thyroid hyperfunction in a patient with long-standing hypothyroidism is uncommon.
      Here, we describe and discuss the unusual scenario of development of severe skin
      rash to carbimazole, with subsequent acute toxicity to lithium in clinically
      indicated doses, in a patient who manifested hyperthyroidism after being on
      treatment for hypothyroidism for 7 years.

PMID- 22854237
TI  - Bortezomib-induced thrombotic thrombocytopaenic purpura.
AB  - Thrombotic thrombocytopaenic purpura (TTP) is a thrombotic microangiopathy
      characterised by haemolytic anaemia, schistocytes on peripheral blood smear and
      thrombocytopaenia that can additionally present with fever, renal insufficiency
      and/or neurological abnormalities. While our understanding of idiopathic TTP has
      significantly advanced, there are still many unanswered questions regarding the
      pathophysiology of secondary TTP, which can be associated with malignancy,
      pregnancy, HIV infection, bone marrow transplantation and exposure to certain
      drugs including several chemotherapeutic agents. Here we present a case of
      bortezomib-associated TTP. Our patient developed microangiopathic haemolytic
      anaemia, thrombocytopaenia and altered mental status after her ninth dose of
      bortezomib. The drug was subsequently discontinued and the patient underwent one
      session of plasma exchange with clinical improvement and recovery of her platelet
      counts, disappearance of schistocytes and resolution of both neurological
      symptoms and haemolysis in 2 days.

PMID- 22854238
TI  - Varicella infection in a neonate with subsequent staphylococcal scalded skin
      syndrome and fatal shock.
AB  - A male term neonate, at day 23 of life, presented with vesicular lesions over the
      trunk, which spread to allover the body on the next day. Five days later, he
      started developing blistering of the skin over the trunk and extremities, which
      subsequently ruptured, leaving erythematous, tender raw areas with peeling of the
      skin. The mother had vesicular eruptions, which started on the second day of
      delivery and progressed over the next 3 days. Subsequently, similar eruptions
      were noticed in two of the siblings before affecting the neonate. On the basis of
      the exposure history and clinical picture, a diagnosis was made of varicella
      infection with staphylococcal scalded skin syndrome (SSSS). The blood culture and
      the wound surface culture grew Staphylococcus aureus. Treatment included
      intravenous fluid, antibiotics, acyclovir and wound care. However, after 72 h of
      hospitalisation, the neonate first developed shock, refractory to fluid boluses,
      vasopressors and catecholamine along with other supports; and he then succumbed.
      In all neonates, staphylococcal infection with varicella can be fatal due to
      SSSS, the toxic shock syndrome or septicaemia.

PMID- 22854239
TI  - Klippel-Trenaunay syndrome complicating pregnancy.
AB  - The Klippel-Trenaunay syndrome is a rare congenital disorder that affects one or
      more limbs. It is characterised by cutaneous vascular nevi, venous malformations
      and hypertrophy of soft tissues and bone. There are very few cases reported in
      pregnant women, so the level of uncertainty is high when it appears during
      gestation. It is a disease that increases obstetric risk and can exacerbate
      complications, mainly thromboembolic and haemorrhagic. We report below the case
      of a pregnant woman diagnosed with this syndrome and the multidisciplinary
      management held in our centre.

PMID- 22854240
TI  - Trans-anal barotrauma by compressed air leading to sigmoid perforation due to a
      dangerous practical joke.
AB  - To present a case report of trans-anal barotrauma by high-pressure compressed air
      jet as a dangerous practical joke, that is, playful insufflation of high-pressure
      air jet through the anal orifice resulting in sigmoid perforation. The patient
      presented to emergency a day later with complaints of severe pain in the abdomen
      and abdominal distension following insufflation of high-pressure air jet through
      the anus. On examination, he had signs suggestive of perforation peritonitis and
      x-ray of the abdomen showed gas under the diaphragm. An emergency exploratory
      laparotomy was performed which revealed a 4-cm perforation in the sigmoid colon.
      Resection of the segment containing perforation along with the surrounding
      devitalised part was done with double-barrel colostomy. Reversal of colostomy was
      done after 8 weeks. Follow-up was uneventful.

PMID- 22854241
TI  - Fulminant type 1 diabetes mellitus.
AB  - We present a fatal case of fulminant type 1 diabetes mellitus that was initially
      diagnosed as upper respiratory tract infection based on pharyngeal redness at a
      clinic. However, the patient then went into cardiopulmonary arrest, and was
      transferred to our hospital for treatment. Testing revealed very high levels of
      blood glucose (86.9 mmol/l), urinary glucose (2+) and ketones (4+). His
      glycosylated haemoglobin level was almost normal (6.2%; normal <6.2%). Autopsy
      revealed marked depletion and atrophy of the islets of Langerhans.

PMID- 22854242
TI  - An incidental peri-adrenal cystic lesion.
AB  - A 50-year-old man was found to have an incidental peri-adrenal cystic lesion on
      CT imaging which was removed laparoscopically. Histological examination showed a
      cystic structure composed of respiratory and cuboidal-type epithelium with
      underlying smooth muscle, cartilage and seromucinous glands. The differential
      diagnosis for such a lesion includes bronchogenic cyst or teratoma
      differentiated. This case report offers an overview of both the conditions and
      the difficulties encountered in the histological distinction.

PMID- 22854243
TI  - UV radiation and skin cancer: the science behind age restrictions for tanning
      beds.

PMID- 22854244
TI  - Yttrium decreases the intracellular Zn2+ concentration in rat thymocytes by
      attenuating a temperature-sensitive Zn2+ influx.
AB  - Yttrium is used in the production of various electronic devices because the alloy
      it contains enhances or modifies the properties of other elements. In order to
      study the cytotoxic action of yttrium, the effect of yttrium chloride (YCl(3)) on
      the intracellular Zn(2+) level was examined in rat thymocytes using a flow
      cytometer with FluoZin-3-AM and propidium iodide. The application of YCl(3)
      significantly decreased the intensity of the FluoZin-3 fluorescence, suggesting a
      decrease in the intracellular Zn(2+) level or quenching of the FluoZin-3
      fluorescence by Y(3+). However, since Y(3+) did not attenuate the FluoZin-3
      fluorescence under cell-free conditions, the latter suggestion was ruled out. Rat
      thymocytes possess a temperature-sensitive membrane pathway that carries Zn(2+)
      into the cells. The application of YCl(3) attenuated the FluoZin-3 fluorescence
      augmented by externally applied ZnCl(2) in a concentration-dependent manner. This
      suggested that Y(3+) inhibited the Zn(2+) influx, resulting in the decrease in
      the intracellular Zn(2+) level. Yttrium may induce dyshomeostasis of
      intracellular Zn(2+), leading to some cytotoxic actions.

PMID- 22854245
TI  - Evaluation of physician eye lens doses during permanent seed implant
      brachytherapy for prostate cancer.
AB  - Treatment of low grade prostate cancer with permanent implant of radioactive
      seeds has become one of the most common brachytherapy procedures in use today.
      The implant procedure is usually performed with fluoroscopy image guidance to
      ensure that the seeds are deployed in the planned locations. In this situation
      the physician performing the transperineal implant is required to be close to the
      fluoroscopy unit and dose to the eye lens may be of concern. In 1991 the
      International Commission on Radiological Protection (ICRP) provided a recommended
      dose limit of 150 mSv yr(-1) for occupational exposures to the lens of the eye.
      With more long term follow-up data, this limit was revised in 2011 to 20 mSv yr(
      1). With this revised limit in mind, we have investigated the dose to the lens of
      the eye received by physicians during prostate brachytherapy seed implantation.
      By making an approximation of annual workload, we have related the dose received
      to the annual background dose. Through clinical and phantom measurements with
      thermoluminescent dosimeters, it was found that the excess dose to the
      physician's eye lens received for a conservative estimate of annual workload was
      never greater than 100% of the annual background dose.

PMID- 22854246
TI  - Meaningful comparison of robotics versus laparoscopy for nephron-sparing surgery:
      no contest or no dice?

PMID- 22854247
TI  - Is traditional laparoscopy the real competitor of robot-assisted partial
      nephrectomy?

PMID- 22854248
TI  - Initial prostate biopsy: development and internal validation of a biopsy-specific
      nomogram based on the prostate cancer antigen 3 assay.
AB  - BACKGROUND: Urinary prostate cancer antigen 3 (PCA3) assay in combination with
      established clinical risk factors improves the identification of men at risk of
      harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE: To develop
      and validate internally the first IBX-specific PCA3-based nomogram that allows an
      individual assessment of a man's risk of harboring any PCa and high-grade PCa
      (HGPCa). DESIGN, SETTING, AND PARTICIPANTS: Clinical and biopsy data including
      urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within
      two prospective multi-institutional studies. INTERVENTION: IBX (>= 10 biopsy
      cores) with standard risk factor assessment including prebiopsy urinary PCA3
      measurement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCA3 assay cut-off
      thresholds were investigated. Regression coefficients of logistic risk factor
      analyses were used to construct specific sets of PCA3-based nomograms to predict
      any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and
      HGPCa were quantified using area under the curve of the receiver operator
      characteristic analysis and compared with a clinical model. Bootstrap resamples
      were used for internal validation. Decision curve analyses quantified the
      clinical net benefit related to the novel PCA3-based IBX nomogram versus the
      clinical model. RESULTS AND LIMITATIONS: Any PCa and HGPCa were diagnosed in 46%
      (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital
      rectal examination, prostate volume, and PCA3 were independent predictors of PCa
      at IBX (all p<0.001). The PCA3-based IBX nomograms significantly outperformed the
      clinical models without PCA3 (all p<0.001). Accuracy was increased by 4.5-7.1%
      related to PCA3 inclusion. When applying nomogram-derived PCa probability
      thresholds <= 30%, only a few patients with HGPCa (<= 2%) will be missed while
      avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based
      IBX-specific nomogram is warranted. CONCLUSIONS: The internally validated PCA3
      based IBX-specific nomogram outperforms a clinical prediction model without PCA3
      for the prediction of any PCa, leading to the avoidance of unnecessary biopsies
      while missing only a few cases of HGPCa. Our findings support the concepts of a
      combination of novel markers with established clinical risk factors and the
      superiority of decision tools that are specific to a clinical scenario.

PMID- 22854250
TI  - Two-dimensionally-guided M-mode and pulsed wave Doppler echocardiographic
      evaluation of the ventricles of apparently healthy cats.
AB  - OBJECTIVE: To determine two-dimensionally-guided (2D-guided) M-mode and pulsed
      wave (PW) Doppler echocardiographic reference intervals range of healthy non
      sedated cats. ANIMALS: Fifty-three healthy, unsedated domestic cats. MATERIALS
      AND METHODS: Cats were interrogated via standard imaging planes with 2D-guided PW
      Doppler, using 5.0 and 7.5 MHz duplex imaging transducers. Left ventricular (LV)
      M-mode measurements and intracardiac PW Doppler data were acquired using ACVIM
      guidelines for echocardiography. Doppler variables of the same region, measured
      from different views, were compared for agreement where appropriate. Descriptive
      statistics were provided for all measured variables. Statistical comparisons of
      selected M-mode and PW Doppler echocardiographic variables and correlations with
      weight or age were made, with significance set at P < 0.01. RESULTS: Most cats
      (42/51) had diastolic LV septal and posterior wall diastolic dimensions <4.5 mm
      (maximum = 5.7 mm). Only septal diastolic wall dimension correlated weakly with
      body weight (rho = 0.36). Median peak transvalvular velocities (m/s) were: aorta
      1.04 (range: 0.77-1.40); LV inflow 0.60 (range: 0.43-0.95) (E wave), 0.47 (range:
      0.32-0.76) (A wave), RV inflow 0.56 (range: 0.37-0.85), pulmonic valve (right)
      0.96 (range: 0.65-1.21). For mitral valve inflow, the E and A waves were usually
      separately measurable at heart rates ~ <180/min, merging into a single diastolic
      wave (EA) at heart rates ~ >190/min. Peak E wave velocity correlated with heart
      rate. No variables correlated with age. CONCLUSIONS: Our study provides
      comprehensive 2D-guided echocardiographic M-mode and PW Doppler reference data
      for apparently healthy cats.

PMID- 22854251
TI  - Effect of lactation on functional and morphological echocardiographic variables
      in adult dairy cows.
AB  - OBJECTIVES: To study the effect of pregnancy and lactation on echocardiographic
      parameters in Holstein dairy cows. ANIMALS: Nine multiparous high milk producing
      (HMP) dairy cows (producing more than 40 kg of milk per day in peak production)
      and 9 low milk producing (LMP) cows (producing less than 30 kg or milk per day in
      peak production). METHODS: Echocardiography was performed twice; one month before
      calving and two months after calving. RESULTS: The heart rate of HMP cows in the
      early lactation period was significantly higher than in the dry period. In LMP
      cows, there was a significant increase in left ventricular dimension in the early
      lactation period as compared to the dry period, and the interventricular septum
      in systole (IVSs) in the dry period was significantly thicker than early
      lactation period. In HMP cows, there was an increase in the right ventricular
      diameter in systole in the early lactation period as compared to the dry period.
      Left ventricular and aortic dimensions in the dry period of HMP were
      significantly higher than those of LMP cows. When the data were corrected for
      body weight, comparison of values of the dry period of HMP and LMP cows showed
      that left ventricular volume in systole in HMP was significantly higher and that
      IVSs, left ventricular fractional shortening and ejection fraction were
      significantly lower than in LMP cows. CONCLUSIONS: This study demonstrated that
      lactation influences the intracardiac dimensions. The amount of milk production
      can influence echocardiographic parameters in dairy cows.

PMID- 22854249
TI  - Construction of conditional acid ceramidase knockout mice and in vivo effects on
      oocyte development and fertility.
AB  - The number of resting follicles in the ovary and their successful maturation
      during development define the fertile female lifespan. Oocytes, enclosed within
      follicles, are subject to natural selection, and the majority will undergo
      apoptosis during prenatal life through adulthood. Our previous studies revealed
      high levels of the lipid hydrolase, acid ceramidase (AC), in human and mouse
      oocytes, follicular fluid and cumulus cells. In addition, supplementation of in
      vitro fertilization media with recombinant AC enhanced the survival of oocytes
      and preimplantation embryos. Herein we constructed and used a conditional
      knockout mouse model of AC deficiency (cACKO) to further investigate the role of
      this enzyme in oocyte survival in vivo. Immunohistochemical staining, activity
      assays, and western blot analysis revealed that AC expression was high in the
      ovaries of normal mice, particularly in the theca cells. After induction of the
      AC gene knockout with tamoxifen (TM), AC levels decreased in ovaries, and
      ceramide was correspondingly elevated. A novel immunostaining method was
      developed to visualize follicles at various stages, and together with light
      microscopic examination, the transition of the follicle from the secondary to
      antral stage was found to be defective in the absence of AC. Western blot
      analysis showed elevated BAX and PARP expression in TM-treated cACKO mouse
      ovaries compared to control animals. In parallel, the levels of BCL-2 and anti
      Mullerian hormone, a marker of ovarian reserve, were decreased. In addition to
      the above, there was a significant decrease in fertility observed in the TM
      treated cACKO mice. Together, these data suggest that AC plays an important role
      in the preservation of fertility by maintaining low ceramide levels and
      preventing apoptosis of theca cells, thereby promoting survival of the follicle
      during the transition from the secondary to antral stage.

PMID- 22854252
TI  - The intermetacarpal angle screening test for ulnar-sided carpometacarpal fracture
      dislocations.
AB  - PURPOSE: Ulnar-sided carpometacarpal injuries can be difficult to diagnose
      radiographically. We hypothesized that the resting position of the normal hand
      during lateral radiography provides a consistent relationship between the rays
      and that dorsal subluxation of the metacarpal base in fracture-dislocations
      increases the angle between the uninjured index and long metacarpals and the
      injured small metacarpal. METHODS: A control group of 100 consecutive patients
      with normal hand radiographs and a series of 12 patients with known
      carpometacarpal fracture-dislocations were examined. Angles between the index and
      small metacarpal shaft (I-S IMA) and between the long and small metacarpal shaft
      (L-S IMA) were measured on the lateral hand radiograph. RESULTS: In the control
      group, the mean I-S IMA and L-S IMA were both 6 degrees . In the study group, the
      mean I-S IMA was 18 degrees , and the mean L-S IMA was 16 degrees . Intraobserver
      and interobserver reliability was good to excellent for both groups, and a
      statistical difference existed between the normal and study groups. Based on box
      plot analysis of normal and abnormal IMAs, a natural dividing line existed at 10
      degrees . With this dividing line, the I-S IMA had a sensitivity of 92% and a
      specificity of 81%, and the L-S IMA had a sensitivity of 83% and a specificity of
      84%. CONCLUSIONS: Both the I-S IMA and the L-S IMA were useful screening
      measurements on lateral hand radiographs for detection of ulnar-sided
      carpometacarpal fracture-dislocations. When evaluating posttraumatic ulnar-sided
      hand pain, advanced imaging should be considered if the I-S IMA or the L-S IMA is
      greater than 10 degrees .

PMID- 22854253
TI  - The association of hemoglobin A1c with the prevalence of stenosing flexor
      tenosynovitis.
AB  - PURPOSE: Diabetic patients are susceptible to stenosing flexor tenosynovitis
      (FTS) and may have a diminished response to treatment. The purpose of this study
      was to determine whether elevated hemoglobin A1c (HbA1c) levels are associated
      with the development of FTS. METHODS: A review of our diabetic registry
      identified a cohort of patients with diabetes mellitus. We stratified this cohort
      to those with and without a diagnosis of FTS during 2008 based on International
      Classification of Diseases-9 coding (727.00-727.05J). We reviewed charts to
      confirm the diagnosis. For patients diagnosed with FTS, we used the HbA1c
      measurement made closest to the date of diagnosis for analysis. We assessed
      patients without FTS using an average of HbA1c measurements during the same time
      period and performed subgroup analysis based on specified HbA1c levels (group A,
      HbA1c level < 7.0%; group B, HbA1c 7.0% to 7.9%; group C, HbA1c 8.0% to 8.9%;
      group D, HbA1c >= 9.0%). Statistical testing consisted of chi-square analysis,
      odds ratios, and multivariate regression analysis. RESULTS: There were 259,927
      patients in 2008 identified with diabetes mellitus, 3,952 of whom were diagnosed
      with FTS. The period prevalence of FTS in this diabetic population was 1.5%.
      Multivariate regression analysis revealed that HbA1c greater than 7% was an
      independent risk factor for FTS (odds ratio/confidence interval: group B,
      1.31/1.20-1.42; group C, 1.35/1.21-1.51; group D, 1.23/1.10-1.38). CONCLUSIONS:
      The prevalence of FTS in this diabetic population was considerably lower than
      expected and may represent a more accurate assessment given the power of this
      population-based study. In addition, the development of FTS appears to be
      associated with higher HbA1c levels. Although further study is necessary, this
      association may be relevant when evaluating and treating diabetic patients with
      trigger finger.

PMID- 22854254
TI  - Interfragmentary compression profile of 4 headless bone screws: an analysis of
      the compression lost on reinsertion.
AB  - PURPOSE: To evaluate the interfragmentary compression force generated by 4
      different types of headless compression screws and to examine the effects of
      removal and reinsertion of the screw. METHODS: We chose foot bones rather than
      scaphoids for the model because they were larger and would enable comparison of 2
      screw designs in the same bone, thereby controlling for the effect of
      interspecimen variability. A transverse osteotomy was made in 10 fresh-frozen
      cadaveric navicular bones and 10 medial cuneiforms. A load cell was used to
      measure compression between the 2 fragments as a screw was inserted across the
      fracture. Each bone was tested twice, with an Acutrak Mini (Acumed, Hillsboro,
      OR; n = 10) and an SBi AutoFIX screw (SBi, Morrisville, PA; n = 10) or an
      Extremifix (Osteomed, Addison, TX; n = 10) and a Barouk screw (Depuy, Warsaw, IN;
      n = 10). Compression was recorded at initial insertion and on removal and
      reinsertion of the screw twice to the same position. Compression was also
      measured after one additional full turn further than the initial position.
      RESULTS: The mean interfragmentary compression generated by the Acutrak Mini
      screw was greater than that of the SBi AutoFIX screw (96 N vs 22 N). There was a
      trend toward a greater mean compression generated by the Extremifix screw
      compared to the Barouk screw (85 N vs 22 N). There was a significant loss of
      compression upon removal and reinsertion of the screws. An additional full turn
      of the screw was able to re-establish a large proportion of the original
      compression. CONCLUSIONS: The compression forces achieved by headless screw
      systems appeared to vary according to the screw design, depth of insertion, and
      the quality of the bone. Substantial compression was lost if the screw was
      removed and replaced. Some screw designs appeared to require a greater depth of
      insertion to achieve effective compression, and the number of additional turns
      required to re-establish compression might vary according to the thread design.
      CLINICAL RELEVANCE: Surgeons should be aware of the compression profile of each
      screw design and the effect of screw removal and reinsertion in the clinical
      setting of small bone fixation.

PMID- 22854255
TI  - The use of a third metacarpal base osteoarticular flap for treatment of
      metacarpophalangeal joint traumatic defects.
AB  - PURPOSE: To describe the use of a pedicled osteoarticular flap harvested from the
      base of the third metacarpal for the treatment of traumatic defects of the
      metacarpophalangeal (MCP) joints. METHODS: From February 2006 to January 2008, we
      included in the study 15 patients with posttraumatic defects of the MCP joints.
      The mean age of the patients was 35 years. The injured MCP joints were located in
      the thumb (n = 6) and index (n = 4), middle (n = 4), and ring fingers (n = 1). Of
      the 15 patients, 10 presented with acute injuries and 5 with old injuries. At
      follow-up, we assessed active motion and pinch strength and compared all
      measurements with those from the opposite hand. In patients with old MCP joint
      injuries, we also compared preoperative and postoperative motion and pinch
      strength. We assessed hand function using the Disabilities of the Arm, Shoulder,
      and Hand questionnaire. RESULTS: At the final follow-up (mean, 28 mo), the mean
      motion arc of the reconstructed MCP joints and the opposite joints was 46 degrees
      and 91 degrees , respectively, and the mean pinch strength of the injured and
      opposite sides was 5.4 and 7.1 kg, respectively. For the 5 patients with old
      injuries to the fingers, the mean preoperative and postoperative motion arc was 2
      degrees  and 43 degrees , and the mean preoperative and postoperative pinch
      strength was 1.6 and 5.3 kg, respectively. The mean Disabilities of the Arm,
      Shoulder, and Hand score of the entire patient series was 9, whereas the mean
      preoperative and postoperative scores of the 5 patients with old injuries were 44
      and 17, respectively. CONCLUSIONS: The use of a pedicled osteoarticular flap
      harvested from the base of the third metacarpal is a reliable technique for the
      treatment of traumatic defects of the MCP joints.

PMID- 22854256
TI  - Functional outcome of open reduction of chronic perilunate injuries.
AB  - PURPOSE: Perilunate injuries are complex and occasionally go unrecognized
      acutely. Open reduction and internal fixation is a valid treatment option for
      these injuries. The purpose of this study was to evaluate the functional outcome
      of treating chronic perilunate injuries with open reduction and internal
      fixation. METHODS: Between 1998 and 2007, we treated 24 patients for chronic
      perilunate injuries. We excluded 5 patients from this study because they
      underwent proximal row carpectomy or limited wrist arthrodesis. We treated the
      remaining 19 patients with open reduction and internal fixation. Mean time from
      injury to surgery was 29 weeks. All patients were men, with a mean age of 27
      years. A total of 13 patients had fracture dislocations (group 1); of these, 11
      were transscaphoid and 2 were transscaphoid transcapitate fracture dislocations.
      Six patients had perilunate dislocations (group 2). RESULTS: Postoperative follow
      up averaged 58 months. All carpal fractures healed at an average of 18 weeks. At
      final evaluation, the average pain scores during rest, daily activities, and
      manual work on a 20-point visual analog scale were 0, 2, and 3, respectively,
      with no significant difference between groups. The active extension and flexion
      of the wrist averaged 39% and 52% of the uninjured side, respectively. Grip
      strength averaged 87% of the uninvolved extremity. According to the Mayo wrist
      scoring system, 58% of all patients (69% of group 1 and 33% of group 2) achieved
      good to excellent results. A total of 18 patients returned to their original work
      activities; 14 patients (74%) were very satisfied. No patients required secondary
      procedures. CONCLUSIONS: Despite late presentation, patients with chronic
      perilunate injuries can be treated with open reduction internal fixation, with
      satisfactory results. Patients with lesser arc injuries have less successful
      outcome. Patients with irreducible dislocations or major articular damage may
      require wrist salvage procedures.

PMID- 22854257
TI  - Assessment of pronator quadratus repair integrity following volar plate fixation
      for distal radius fractures: a prospective clinical cohort study.
AB  - PURPOSE: To assess prospectively the integrity of pronator quadratus (PQ) muscle
      repair following volar plate fixation of distal radius fractures and to compare
      the clinical and radiographic outcomes of durable versus failed repairs in 24
      subjects. In addition, by grading the degree of PQ injury, an attempt was made to
      correlate failure of repair with the PQ injury severity. METHODS: The extent of
      PQ injury was graded for each fracture. After fracture fixation, the PQ muscle
      was repaired along its radial and distal borders. Radiopaque hemoclips were
      attached to each side of the PQ repair, 2 radially and 2 distally. The distance
      between these markers at time 0 versus x-rays taken at approximately 2 weeks, 6
      weeks, and 3 months was recorded. Clip displacement of 1 cm or more compared to
      time 0 indicated repair failure. RESULTS: One of 24 repairs (4%) failed at 3
      months. No statistical difference was noted between the type of PQ injury and
      wrist flexion/extension, pronation/supination, and grip strength. CONCLUSIONS:
      Pronator quadratus repairs after volar plate fracture fixation are generally
      durable. They withstand forces that occur at the distal radius during the healing
      process with a 4% failure rate. No correlation was shown between type of PQ
      injury and radiographic failure of the repair.

PMID- 22854258
TI  - Atypical pyoderma gangrenosum of the dorsal hand mimicking squamous cell
      carcinoma.
AB  - We describe a rare case of atypical pyoderma gangrenosum of the dorsal hand in a
      patient who presented with the histopathologic diagnosis of squamous cell
      carcinoma (SCC). Atypical pyoderma gangrenosum is a rare variant of pyoderma
      gangrenosum that occurs on the upper extremities, presenting as a cutaneous
      ulcer. The correct treatment is nonsurgical, and surgical intervention often
      results in trauma-induced expansion of lesions. Pyoderma gangrenosum, most
      commonly mistaken for infection, has resulted in amputation. Histologic and
      clinical presentation 1 month after onset of symptoms in the patient reported
      here mimicked SCC. Awareness by hand surgeons of the possible histologic
      misdiagnosis of SCC at an early stage in the disease evolution and a high index
      of suspicion in the face of biopsy-proven SCC may prevent unnecessary digit
      amputation.

PMID- 22854259
TI  - Risk factors and prevalence rate of restless legs syndrome among pregnant women
      in Taiwan.
AB  - BACKGROUND: The goal of this study was to assess the prevalence and clinical
      correlates of restless legs syndrome (RLS) among pregnant Taiwanese women.
      METHODS: We enrolled 461 pregnant women (18-45 years) admitted at Mackay Memorial
      Hospital for delivery from September 2010 to May 2011. The face-to-face
      questionnaire used to gather data included assessment of RLS diagnostic criteria,
      and questions related to RLS. RESULTS: The overall prevalence rate of RLS among
      the study participants was 10.4%; 2.8% were categorized as having chronic RLS.
      Participants without RLS reported higher folate and iron supplement consumption
      than those with RLS. Multivariate analysis revealed significant associations of
      RLS with anemia and peptic ulcer disease. Participants with transient RLS during
      pregnancy reported more regular coffee consumption before pregnancy, and better
      sleep latency, duration, and efficiency, than those with chronic RLS. Overall,
      81.2% of RLS sufferers reported sleep disturbances. CONCLUSIONS: Our study
      revealed highly prevalent but poorly recognized RLS among Taiwanese pregnant
      women. The identification of predictors such as medical comorbidities, and
      protectors such as folate and iron supplements, is warranted for obstetric RLS.
      In most cases, symptoms began during the second or third trimester and resolved
      within a week after delivery. Restricted coffee consumption before pregnancy is
      encouraged, but further evidence is needed to support this recommendation.

PMID- 22854260
TI  - Decreased levels of total immunoglobulin in children with autism are not a result
      of B cell dysfunction.
AB  - Autism spectrum disorders are a heterogeneous group of behaviorally defined
      disorders having complex etiologies. We previously reported a direct correlation
      between lower plasma levels of the immunoglobulins (Ig) IgG and IgM and increased
      severity of behavioral symptoms in children with autism. Our current objective
      was to determine if these reduced plasma levels of IgG and IgM are the result of
      defective B cell development, activation, or function. Results suggest no
      differences in the B cell parameters measured, indicating that decreased Ig in
      autism is not a result of B cell dysfunction and other immune cells might be
      involved.

PMID- 22854261
TI  - Bilateral basal ganglia activity in verbal working memory.
AB  - Although the cortical substrates of verbal working memory are reasonably well
      understood, less is known about the relative contribution of subcortical
      structures to verbal working memory. Therefore, in addition to elaboration of a
      model of verbal working memory by including a specific focus on basal ganglia,
      the purpose of this study also was to examine potential differences in neural
      function across the complete process of verbal working memory, from encoding
      through retrieval. Functional magnetic resonance imaging was used to observe
      regions of brain activation in neurologically normal participants during a task
      of verbal working memory. The expected frontal-parietal network was found to be
      active over the course of the verbal working memory task. The encoding portion of
      the task engaged left inferior frontal regions and bilateral caudate and
      thalamus. Bilateral medial thalamus and posterior cingulate regions were engaged
      during the maintenance phase of the task. Retrieval activated the left inferior
      frontal sulcus and posterior parietal/occipital regions. Findings are considered
      in light of current models of verbal working memory and subcortical structures.

PMID- 22854262
TI  - Nonionic diethanolamide amphiphiles with saturated hydrocarbon chains: neat
      crystalline and lyotropic liquid crystalline phase behavior.
AB  - The solid state and lyotropic phase behavior of a series of nonionic
      diethanolamide amphiphiles with increasing saturated hydrocarbon chain length
      (lauroyl, myristoyl, palmitoyl, and stearoyl) has been examined. All four
      saturated diethanolamide amphiphiles form a crystalline solid with two or three
      different polymorphic crystalline forms at room temperature. Melting points and
      associated enthalpies for these four amphiphiles increased with increasing chain
      length. Approximate partial binary phase diagrams have been constructed for each
      amphiphile/water system by combining Cross-Polarized Optical Microscopy (POM) and
      Small-Angle X-ray Scattering (SAXS) results. In the presence of water, all four
      diethanolamides form an L(alpha) phase, between 10% and 50% water content, and an
      L(2) phase with decreasing hydration and increasing temperature. In addition to
      the L(alpha) and L(2) phases, the shorter chain diethanolamide amphiphiles
      (lauroyl and myristoyl) also display a normal micellar phase (L(1)) at higher
      water contents, occurring to lower temperatures than the L(alpha) phase. By
      examining the effect of subtle molecular changes on both neat and lyotropic phase
      behavior, amphiphiles can be designed with properties tailored to a desired
      application.

PMID- 22854263
TI  - IL-6 activates STAT5 in T cells.
AB  - BACKGROUND: IL-6 is a pleiotropic cytokine which emerged recently as a key
      regulator of CD4 T cell function. IL-6 alone or in combination with other
      cytokines promotes T helper 1, T helper 17 and T follicular helper cell
      differentiation whilst inhibiting the induction of regulatory T cell generation.
      IL-6 activates multiple pathways among which JAK/STAT3 is the most clearly
      validated in the control of CD4 T helper differentiation. Activation of STAT5 by
      cytokines such as IL-2 can counteract IL-6-induced T helper 17 and T follicular
      helper cell differentiation and promote the induction of regulatory T cell
      generation. STAT5 and STAT3 are known to compete for promoter binding sites in
      CD4 T cells and the two transcription factors are believed to have opposite
      functions in the control of CD4 T cell differentiation. METHODS: We analyzed IL-6
      induced STAT1, 3 and 5 activation by flow cytometry (phosflow) in mouse
      mononuclear cells and its effect on the level of the mRNA coding for cytokine
      inducible SH2-containing protein (CIS). RESULTS: The results show that IL-6 also
      induces STAT5 activation in both CD4 and CD8 T as well as NK cells. Analysis of
      STAT5 phosphorylation in CD4 T cells indicates that it is transient and requires
      higher cytokine concentrations than that of STAT3. CD4 T cell stimulation with IL
      6 induces the synthesis of CIS, which is encoded by a gene known to be regulated
      by STAT5. CONCLUSIONS: Thus, IL-6 at concentrations corresponding to levels
      observed in the serum during inflammation may activate, in CD4 T cells, a STAT5
      negative feedback loop which alters the balance between STAT3-dependent pro
      inflammatory helper T cells and STAT5-induced T regulatory cells. STAT5
      activation may modulate the differentiation of T helper cells through attenuation
      of TGF-beta stability and production. Since STAT5 is directly activated by Janus
      kinases, therapeutic approaches designed to inhibit STAT3 activation or to
      recruit STAT3 phosphatases may be useful in altering the balance of activated
      STAT3 and STAT5 in favor a profile that would be beneficial in pathologies
      involving IL-6.

PMID- 22854265
TI  - Flavors of uncertainty: the difference between denial and debate.

PMID- 22854264
TI  - Pseudorabies virus and herpes simplex virus type 1 utilize different tegument
      glycoprotein interactions to mediate the process of envelopment.
AB  - BACKGROUND AND OBJECTIVE: During herpesvirus envelopment capsids, tegument
      polypeptides and membrane proteins assemble at the site of budding, and a
      cellular lipid bilayer becomes refashioned into a spherical envelope. A web of
      interactions between tegument proteins and the cytoplasmic tails of viral
      glycoproteins play a critical role in this process. We have previously
      demonstrated that for herpes simplex virus (HSV)-1 the cytoplasmic tail of
      glycoprotein H (gH) binds the tegument protein VP16. The HSV and pseudorabies
      virus (PRV) genomes are essentially collinear, and individual gene products show
      significant sequence homology. However, the demarcation of function often differs
      between PRV and HSV proteins. The goal of this study was to determine whether PRV
      gH and VP16 interact in a manner similar to their homologs in HSV. METHODS: A
      fusion protein pull-down assay was performed in which a PRV gH cytoplasmic tail
      glutathione S-transferase fusion protein, bound to glutathione-Sepharose beads,
      was incubated with PRV-infected cell cytosol, washed and subjected to Western
      blot analysis using anti-PRV VP16 antisera. RESULTS: Western blots indicate that
      PRV VP16 does not specifically bind to the PRV gH tail. CONCLUSION: Our results
      highlight that, despite the relatively close evolutionary relationship between
      HSV and PRV, there are significant differences in their protein interactions that
      drive envelopment.

PMID- 22854266
TI  - Ultrasound of the abdominal wall: what lies beneath?
AB  - Clinically equivocal abdominal wall lesions often pose diagnostic dilemmas for
      clinicians. It can be equally challenging to appreciate the nature of abdominal
      wall lesions found incidentally on abdominal ultrasound examinations. Ultrasound
      is a non-ionizing, cheap, and easily accessible investigation for such lesions.
      It is widely used and has the added advantage of being a dynamic investigation.
      However, imaging with ultrasound is operator-dependent and relies on technical
      skills. It is important to understand the imaging of normal anatomy and to be
      familiar with the imaging appearance of lesions. We present a review of various
      lesions seen during ultrasound examinations of the abdominal wall or as
      incidental findings on abdominal ultrasound.

PMID- 22854267
TI  - Cost-effectiveness in the contemporary management of critical limb ischemia with
      tissue loss.
AB  - BACKGROUND: The care of patients with critical limb ischemia (CLI) and tissue
      loss is notoriously challenging and expensive. We evaluated the cost
      effectiveness of various management strategies to identify those that would
      optimize value to patients. METHODS: A probabilistic Markov model was used to
      create a detailed simulation of patient-oriented outcomes, including clinical
      events, wound healing, functional outcomes, and quality-adjusted life-years
      (QALYs) after various management strategies in a CLI patient cohort during a 10
      year period. Direct and indirect cost estimates for these strategies were
      obtained using transition cost-accounting methodology. Incremental cost
      effectiveness ratios (ICERs), in 2009 U.S. dollars per QALYs, were calculated
      compared with the most conservative management strategy of local wound care with
      amputation as needed. RESULTS: With an ICER of $47,735/QALY, an initial surgical
      bypass with subsequent endovascular revision(s) as needed was the most cost
      effective alternative to local wound care alone. Endovascular-first management
      strategies achieved comparable clinical outcomes but at higher cost (ICERs
      >=$101,702/QALY); however, endovascular management did become cost-effective when
      the initial foot wound closure rate was >37% or when procedural costs were
      decreased by >42%. Primary amputation was dominated (less effectiveness and more
      costly than wound care alone). CONCLUSIONS: Contemporary clinical effectiveness
      and cost estimates show an initial surgical bypass is the most cost-effective
      alternative to local wound care alone for CLI with tissue loss and can be
      supported even in a cost-averse health care environment.

PMID- 22854268
TI  - Inflammation in the walls of asymptomatic abdominal aortic aneurysms is not
      associated with increased metabolic activity detectable by 18-fluorodeoxglucose
      positron-emission tomography.
AB  - OBJECTIVE: We hypothesized that the general inflammation observed in the wall of
      large, asymptomatic abdominal aortic aneurysms (AAAs) could be detected in vivo
      by 18-fluorodeoxglucose (FDG) positron-emission tomography (PET) and, if so, that
      this method could be used to study if active inflammation is an early
      pathogenetic finding in small AAAs detected by screening. METHODS: In this
      prospective clinical study, 12 men were examined with FDG-PET computed
      tomography. Seven had large asymptomatic AAAs (range, 52-66 mm) that required
      surgery, and five had small AAAs (range, 34-40 mm) under surveillance. In the
      surgery group, biopsy specimens were taken from the aneurysm wall for histologic
      examinations. RESULTS: Compared with normal segments of the aorta, liver, and
      blood and compared with healthy controls matched for age and sex, no increased
      FDG uptake, measured as standardized uptake value, was detected in any of the
      large or small AAAs. The SUV(mean) difference between infrarenal aorta and blood
      was -0.3 for cases and -0.1 for controls (P = .06). The corresponding differences
      between the infrarenal aorta and liver was -0.8 and -0.8 (P = .91) and between
      infrarenal aorta and suprarenal aorta was -0.2 and -0.1 for cases and controls,
      respectively (P = .20). The histologic examination of the aneurysm walls showed
      high inflammatory cell infiltration with T lymphocytes, B lymphocytes, and
      macrophages. CONCLUSIONS: The chronic inflammation observed in the wall of
      asymptomatic AAAs was not sufficiently metabolically active to result in an
      increased glucose metabolism detectable by FDG-PET by means of this standard
      protocol. To study the importance of inflammation in the pathogenesis of AAAs in
      vivo, PET tracers other than FDG need to be developed.

PMID- 22854269
TI  - Reduplicative paramnesia: a review.
AB  - BACKGROUND: Reduplicative paramnesia (RP) is a content-specific delusional
      misidentification syndrome (DMS) which has received little attention in the
      research literature relative to other DMS. RP is thought to result from an
      organic rather than psychiatric cause distinguishing it from other DMS. Our
      systematic review examines the research literature investigating the prevalence,
      symptomatology and potential neurologic mechanisms underlying RP. SAMPLING AND
      METHODS: MEDLINE, PsycINFO, and the Cochrane Library were searched (from 1966 to
      February 10, 2012) with the reference lists of relevant articles examined. Case
      reports, clinical studies and post-mortem studies focusing on, or referring to,
      RP were included. RESULTS: There is a paucity of literature regarding the
      potential mechanisms underlying the psychological, cognitive and neurological
      aspects of RP. The available literature is limited by the lack of systematic
      clinical studies and in vivo investigations with current findings remaining only
      speculative. However, there does appear to be a consensus that RP may have a
      neurologic rather than psychiatric cause and that right and bifrontal lesions as
      well as the cognitive dissonance associated with memory, visuospatial and
      impaired conceptual integration are common factors in RP presentation.
      CONCLUSIONS: This area requires further extensive systematic research with
      supplementary in vivo data. Current studies suggest that focal lesions within the
      frontal lobe may account for the onset of RP.

PMID- 22854270
TI  - Relationship of fibroblast growth factor 23 with left ventricle mass index and
      coronary calcificaton in chronic renal disease.
AB  - BACKGROUND: To evaluate the relationship between FGF23 and changes in biochemical
      parameters, left ventricle mass index, coronary, aortic and, valve
      calcifications. METHODS: Totally 185 patients with chronic renal disease were
      included in this prospective, cross-sectional study. The patients were stratified
      according to GFR levels (mL/min/1.73 m2) into 5 groups: >=60, 45-59, 30-44, 15-29
      and <15 (group 1-5 respectively). Biochemical parameters, serum FGF23 levels were
      measured. Echocardiographic assessments and Coronary artery calcification (CAC)
      with multidetector computerized tomography (MDCT) were done, left ventricle
      muscle mass (LVMI) was measured all patients. RESULTS: Left ventricular
      hypertrophy (LVH), aortic and valve calcification were detected in 27.8%, 25.3%
      and 12% of patients respectively. CAC was detected in 18 patients. LVMI and FGF23
      levels were found to increase proportionally with the severity of renal failure.
      A significant positive correlation between FGF-23 level and serum phosphate,
      logPTH, and CaxP product was found. While a correlation between FGF-23 and valve
      calcification was detected, no correlation could be detected with LVMI, LVH,
      coronary and aortic calcification. CONCLUSION: In CKD, circulating FGF-23 and
      LVMI levels gradually increase with declining renal function such that by the
      time patients reach end-stage renal disease. Correlation between logFGF23 and
      valve calcification was significant, whereas no statistically significant
      relationship was found between logFGF23 and LVMI, LVH, aortic and coronary artery
      calcifications.

PMID- 22854271
TI  - Novel indomethacin action: selective and direct activation of protein kinase C
      epsilon.
AB  - BACKGROUND/AIMS: In our earlier study, indomethacin potentiated alpha7
      acetylcholine (ACh) receptor responses by activating protein kinase C (PKC). The
      present study was conducted to gain further insight into the indomethacin action
      on PKC. METHODS: PKC activity was assayed in PC-12 cells or under the cell-free
      conditions. PKC-epsilon was knocked-down using the siRNA to silence the PKC
      epsilon-targeted gene. A fluorescein-conjugated indomethacin was synthesized to
      examine the interaction of indomethacin with PKC-epsilon. RESULTS: In the in situ
      PKC assay, indomethacin activated PKC in PC-12 cells in a concentration (1-100
      uM)-dependent manner, and the activation was suppressed by knocking-down PKC
      epsilon. In the cell-free PKC assay, indomethacin (100 uM) activated PKC-epsilon
      in the absence of diacylglycerol, phosphatidylserine, and calcium, but other PKC
      isozymes such as alpha, betaIota, betaIotaIota, gamma, delta, iota, and zeta were
      not activated. In the indomethacin binding assay using a fluorescent-conjugated
      indomethacin on blue native-polyacrylamide gel electrophoresis (blue native
      PAGE), a fluorescent signal was detected at the site consistent with PKC-epsilon
      protein and the signal was attenuated by adding non-conjugated indomethacin or
      eliminated by pretreatment with non-conjugated indomethacin. CONCLUSION: The
      results of the present study show that indomethacin has the potential to
      selectively activate PKC-epsilon through its direct binding, independently of
      cyclooxygenase (COX) inhibition.

PMID- 22854272
TI  - Natural radioactivity in building material in the European Union: robustness of
      the activity concentration index I and comparison with a room model.
AB  - Using a wide database collected in the last 10 years, the authors have calculated
      the activity concentration index I for many building materials in the European
      Union. Suggested by a European technical guidance document, the index I has
      recently been adopted as a screening tool in the proposal for the new Euratom
      basic safety standards directive. The paper analyses the possible implications of
      the choice of different parameters for the computation of index I, i.e.
      background to be subtracted, dose criteria, etc. With the collected data an
      independent assessment of gamma doses was also made with an ISS room model,
      choosing reasonable hypotheses on the use of materials. The results of the two
      approaches, i.e. index I and a room model, were compared.

PMID- 22854273
TI  - Detection and management of perinatal depression by midwives.

PMID- 22854274
TI  - Direct detection of phoxim in water by two-dimensional correlation near-infrared
      spectroscopy combined with partial least squares discriminant analysis.
AB  - This paper has established a simple method to detect directly phoxim in water. In
      the light of two-dimensional correlation analysis, the band of wavenumber for
      near-infrared spectroscopy of the model is between 5364.8 and 7552.9 cm(-1), the
      rate of accuracy for partial least squares discriminant analysis to calibration
      set (n=149) is 100%, prediction set (n=75) is 93.3% and the overall rate of
      accuracy for all the samples is 97.8% under the limit of detection 1 MUg ml(-1)
      owing to the spectra preprocessing by standard normal variate transformation and
      multiplicative scatter correction. It is made clear that this method (two
      dimensional correlation analysis combined with partial least squares discriminant
      analysis) is effective to detect directly phoxim in water.

PMID- 22854275
TI  - Midbrain and falx in fetuses with absent corpus callosum at 11-13 weeks.
AB  - OBJECTIVE: To describe the first trimester diagnosis of agenesis of the corpus
      callosum (ACC). METHODS: The midbrain and falx cerebri were examined in stored
      images of the midsagittal view of the fetal brain at 11(+0)-13(+6) weeks'
      gestation from 15 fetuses with ACC and 500 normal controls. The midbrain diameter
      and falx diameter were measured and their ratio was calculated. The values in
      fetuses with ACC and normal controls were compared. RESULTS: In the control
      group, the midbrain and falx diameters increased significantly with crown-rump
      length (CRL) from respective mean values of 5.1 and 6.9 mm at CRL of 45-6.9 mm
      and 12.1 mm at CRL of 84 mm. In the ACC group the midbrain diameter was above the
      95th percentile of the control group in 8 (53.3%) cases, the falx diameter was
      below the 5th percentile in 6 (40.0%) cases and the midbrain diameter-to-falx
      diameter ratio was above the 95th percentile in 13 (86.7%) cases. CONCLUSIONS: In
      the midsagittal view of the fetal brain at 11-13 weeks, the majority of fetuses
      with ACC have measurable abnormalities in the midbrain and falx area of the
      brain.

PMID- 22854276
TI  - Health effects of chronic noise exposure in pregnancy and childhood: a systematic
      review initiated by ENRIECO.
AB  - BACKGROUND: Chronic noise is an environmental pollutant and well-known to cause
      annoyance and sleep disturbance. Its association with clinical and subclinical
      adverse health effects has been discussed. OBJECTIVES: This systematic review
      aimed to examine associations between chronic noise exposure during pregnancy or
      childhood and health outcomes in early and late childhood. METHODS: Following a
      systematic electronic literature search (MEDLINE, EMBASE), an additional hand
      search and a critical evaluation of potential articles by 2 independent
      reviewers, 29 studies were included: 12 on pregnancy/birth outcomes with samples
      ranging from 115 to 22,761 and 17 on cardiovascular and immune-mediated health
      outcomes in childhood with samples ranging from 43 to 1542. Evidence levels (3 to
      2++) were rated according to the Scottish Intercollegiate Guidelines Network.
      RESULTS: Chronic noise exposure during pregnancy was not associated with birth
      weight, preterm birth, congenital anomalies, perinatal and neonatal death based
      on 6 cohort, 4 case-control, and 2 cross-sectional studies (highest evidence
      level 2+). There was some evidence supporting an association of chronic noise
      exposure with increased systolic blood pressure and stress hormone levels in
      urine and saliva in children evaluating 2 cohort and 15 cross-sectional studies
      (highest evidence level 2-). CONCLUSIONS: There seemed to be no associations
      between chronic noise and pregnancy outcomes based on studies with evidence
      levels up to 2+. Associations between chronic noise and health in children were
      based mainly on cross-sectional studies. However, the studies included in this
      comprehensive systematic review showed a high variation in study design, outcome,
      exposure and confounder assessments.

PMID- 22854277
TI  - Omega-3 fatty acids enhance monocyte-suppressing effect of bezafibrate in
      patients with isolated hypertriglyceridemia.

PMID- 22854278
TI  - Self-reported psychotic symptoms in the general population: correlates in an
      Iranian urban area.
AB  - BACKGROUND: Psychosis exists in the community as a continuum of severity. Here,
      we examine the correlates of self-reported psychotic symptoms in an urban
      catchment area of Iran. SAMPLING AND METHODS: Two thousand one hundred and fifty
      eight participants (age 18-65 years) residing in southern Tehran (the capital
      city of Iran) were interviewed using the psychoticism and paranoia dimensions of
      the Symptom Checklist-90-Revised (SCL-90-R) to assess the severity of psychotic
      symptoms. Other dimensions of the SCL-90-R assessing nonpsychotic symptoms and a
      sociodemographic questionnaire were also used. Paykel's Interview for Recent Life
      Events was used to assess stressful life events. RESULTS: Independent
      associations were observed between younger age, female gender, stressful life
      events and dimensions of depression, anxiety, hostility, obsessive-compulsive
      symptoms and interpersonal sensitivity and psychoticism. Independent associations
      were also observed for marital problems, unemployment, stressful life events and
      dimensions of depression, anxiety, hostility, interpersonal sensitivity and
      phobic anxiety with paranoid ideation. There was also a trend toward an
      association between higher educational levels and the severity of psychotic
      symptoms, particularly paranoid ideation. CONCLUSIONS: Most of the previously
      accepted correlations for psychotic symptoms in the community were replicated. An
      unexpected association between paranoia and female gender, and a trend toward
      higher rates of psychotic symptoms in more educated participants, were in
      contrast with the studies in developed settings. The insufficient coverage of
      psychosis-relevant questions from the SCL-90-R for the entire psychotic
      diagnostic spectrum should be considered a limitation.

PMID- 22854280
TI  - Can a rare form of myasthenia gravis shed additional light on disease mechanisms?
AB  - A healthy 43-year-old physician developed gradually progressive and fluctuating
      fatigable muscle weakness involving ocular, limb, bulbar and respiratory muscles,
      with episodic acute respiratory failure, eventually necessitating intermittent
      non-invasive respiratory support (NIV). A mild short episode occurred 15 years
      earlier with complete resolution. Electromyography (EMG) studies and
      acetylcholine receptor (AchR) antibodies were repeatedly non-diagnostic. The
      diagnosis of myasthenia gravis (MG) was finally confirmed by direct measurement
      of diaphragmatic strength using magnetic nerve stimulation providing clear cut
      evidence of significant fatigable weakness and the demonstration of muscle
      specific kinase (MuSK) serum antibodies using a novel cell-based assay. The
      cluster of several atypical features and lack of response to commonly used
      treatment modalities prompted a search for a unifying mechanism and better
      understanding of the underlying pathophysiology. Review of the literature
      suggested a possible impairment of excitation-contraction coupling with
      malfunction of a signaling protein downstream to the AchR, without an
      accompanying impairment of electrical transmission. This postulated mechanism,
      resulting in a disturbance of calcium signaling, explained the unusual features
      in this patient's illness and led to treatment with salbutamol and ephedrine and
      to significant symptomatic improvement not achieved by any other treatment.

PMID- 22854279
TI  - Prevalence and correlates of child sexual abuse: a national study.
AB  - BACKGROUND: This study examines the prevalence, correlates, and psychiatric
      disorders of adults with history of child sexual abuse (CSA). METHODS: Data were
      derived from a large national sample of the US population. More than 34000 adults
      18 years and older residing in households were interviewed face-to-face in a
      survey conducted during the 2004-2005 period. Diagnoses were based on the Alcohol
      Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, version. Weighted means,
      frequencies, and odds ratios of sociodemographic correlates and prevalence of
      psychiatric disorders were computed. Logistic regression models were used to
      examine the strength of associations between CSA and psychiatric disorders,
      adjusted for sociodemographic characteristics, risk factors, and other Axis I
      psychiatric disorders. RESULTS: The prevalence of CSA was 10.14% (24.8% in men
      and 75.2% in women). Child physical abuse, maltreatment, and neglect were more
      prevalent among individuals with CSA than among those without it. Adults with CSA
      history had significantly higher rates of any Axis I disorder and suicide
      attempts. The frequency, type, and number of CSA were significantly correlated
      with psychopathology. CONCLUSIONS: The high correlation rates of CSA with
      psychopathology and increased risk for suicide attempts in adulthood suggest the
      need for a systematic assessment of psychiatric disorders and suicide risk in
      these individuals. The risk factors for CSA emphasize the need for health care
      initiatives geared toward increasing recognition and development of treatment
      approaches for the emotional sequelae CSA as well as early preventive approaches.

PMID- 22854281
TI  - Furanodiene, a natural product, inhibits breast cancer growth both in vitro and
      in vivo.
AB  - PURPOSE: Previous studies have reported that the Curcuma wenyujin Y.H. Chen et C.
      Ling extract, which has a high furanodiene content, showed anti-cancer effects in
      breast cancer cells in vitro. The present study was designed to evaluate the in
      vitro and in vivo anti-cancer activity of furanodiene. METHODS: The in vitro
      effects of furanodiene were examined on two human breast cancer cell lines, MCF-7
      and MDA-MB-231 cells. Assays of proliferation, LDH release, mitochondrial
      membrane potential (DeltaPsim), cell cycle distribution, apoptosis and relevant
      signaling pathways were performed. The in vivo effect was determined with MCF7
      tumor xenograft model in nude mice. RESULTS: Furanodiene significantly inhibited
      the proliferation and increased the LDH release in both cell lines in a dose
      dependent manner. DeltaPsim depolarization, chromatin condensation, and DNA
      fragmentation were also observed after furanodiene treatment. Furanodiene dose
      dependently induced cell cycle arrest at the G0/G1 phase. The protein expressions
      of p-cyclin D1, total cyclin D1, p-CDK2, total CDK2, p-Rb, total Rb, Bcl-xL, and
      Akt were significantly inhibited by furanodiene, whereas the protein expressions
      of Bad and Bax, and the proteolytic cleavage of caspase-9, caspase-7, and poly
      ADP-ribose polymerase (PARP) were dramatically increased. Furthermore, the z-VAD
      fmk markedly reversed the furanodiene-induced cell cytotoxicity, the proteolytic
      cleavage of caspase-9, and DNA fragmentation but did not affect the proteolytic
      cleavage of PARP, whereas the Akt inhibitor VIII increased the furanodiene
      induced cytotoxicity and PARP cleavage. In addition, furanodiene dose-dependently
      suppressed the tumor growth in vivo, achieving 32% and 54% inhibition rates after
      intraperitoneal injection of 15 mg/kg and 30 mg/kg, respectively. CONCLUSIONS:
      Taken together, we concluded that furanodiene suppresses breast cancer cell
      growth both in vitro and in vivo and could be a new lead compound for breast
      cancer chemotherapy.

PMID- 22854282
TI  - Factor analysis of a health-promoting lifestyle profile (HPLP): application to
      older adults in Mainland China.
AB  - This research reports preliminary psychometric properties, especially the factor
      structure, of a Chinese version of a health-promoting lifestyles profile designed
      for older adults; and examines the distribution of the health-promoting
      behavioral patterns - both for the purpose of developing culturally sensitive
      health advancement strategies for Chinese seniors. Responses to this
      questionnaire were used to measure health-promoting behaviors in a random sample
      of 1012 elderly Chinese from thirty communities in Xi'an Shaanixi-Province.
      DESIGN: Factor analysis relied on polychoric correlations with ordinal
      categorical data were used to evaluate reliability and validity of a revised
      Chinese version of the health-promoting lifestyles profile (HPLP-C). Because this
      revised version was used to assess elderly adults, we termed it the HPLP-CE. This
      factor analysis supported a six-factor model of the original HPLP-C scale.
      Confirmatory factor analysis indicated a good fit, with factors explaining 88.1%
      of the common variance of the HPLP-CE scores. Cronbach's alpha coefficients were
      0.91 for the revised instrument, and ranged from 0.67 to 0.88 for six dimensions.
      The split-half reliability was 0.92, while the test-retest reliability was 0.68.
      Relationships between HPLP-CE, perceived health status, SF-36 scale scores, and
      associations with selected demographic variables were significantly positive.
      CONCLUSIONS: We concluded that this revised scale, based on the 40-item HPLP-C,
      was considered suitable for measuring health-promoting lifestyles of older adults
      in China. Mental and inner self-reflection planes were the most salient factors
      for assessing health-promoting behaviors of seniors. Such factors need to be
      considered if preventive programs are to be designed to promote seniors' health.

PMID- 22854284
TI  - Long-term outcomes after phthalate exposure: food intake, weight gain, fat
      storage, and fertility in mice.

PMID- 22854283
TI  - Molecular identification of a new splicing variant of the MLL - MLLT11 fusion
      transcript in an adult with acute myeloid leukemia and t(1;11)(q21;q23).
AB  - More than 70 different mixed lineage leukemia (MLL) rearrangements involving
      11q23 have been molecularly characterized in acute leukemia. Among these, the
      MLLT11 gene is highly unique as MLL fusion partner because the entire open
      reading frame is usually fused in-frame to the N-terminal portion of the MLL
      gene. By using molecular genetic methods, we identified the chromosomal fusion
      site within MLL exon 10 sequences which were fused to the MLLT11 intron 1
      sequences. This unusual break site results in the creation of two in-frame MLL
      MLLT11 fusion transcripts in this acute myeloid leukemia patient with
      t(1;11)(q21;q23). One fusion transcript represents a normal splice product, while
      the other contains intronic sequences and a cryptic splice event in order to
      generate an intact fusion transcript. We also reviewed all published articles
      which have reported t(1;11)(q21;q23) in myeloid or lymphoid neoplasm and
      attempted to summarize these published data. Of interest, pediatric patients
      displayed a significant larger portion of unique balanced translocations (n =
      40), while complex karyotypes were less often identified (n = 12). Vice versa, in
      adult leukemia patients, complex karyotypes (n = 5) were more frequent than
      unique balanced translocations (n = 2).

PMID- 22854285
TI  - 'Vampirism' in a case of dissociative identity disorder and post-traumatic stress
      disorder.

PMID- 22854287
TI  - Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain
      alpha-reactive CD4 T cells in A/J mice.
AB  - Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in
      myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an
      underlying mechanism, but direct evidence of its role is lacking. To delineate
      autoimmune response in CVB3 myocarditis, we used IA(k) dextramers for cardiac
      myosin heavy chain (Myhc)-alpha 334-352. We have demonstrated that myocarditis
      susceptible A/J mice infected with CVB3 generate Myhc-alpha-reactive CD4 T cells
      and such a repertoire was absent in naive mice as measured by proliferative
      response to Myhc-alpha 334-352 and IA(k) dextramer staining. We also detected
      Myhc-alpha 334-352 dextramer(+) cells in the hearts of CVB3-infected mice. The
      autoreactive T cell repertoire derived from infected mice contained a high
      frequency of interleukin-17-producing cells capable of inducing myocarditis in
      naive recipients. The data suggest that CVB3, a bona fide pathogen of
      cardiovascular system that primarily infects the heart can lead to the secondary
      generation of autoreactive T cells and contribute to cardiac pathology.

PMID- 22854288
TI  - Hemorrhage from the inferior epigastric artery malformation into the external
      intestinal fistula as an atypical complication of Crohn's disease.

PMID- 22854286
TI  - Osteoarthritis-associated basic calcium phosphate crystals induce pro
      inflammatory cytokines and damage-associated molecules via activation of Syk and
      PI3 kinase.
AB  - The pro-inflammatory cytokines, TNFalpha, IL-1 and IL-18, amplify cartilage
      destruction associated with osteoarthritis (OA). Current data suggest that basic
      calcium phosphate (BCP) crystals are potent drivers of inflammatory mediator and
      matrix metalloprotease expression in the OA joint. It has previously been
      demonstrated that synovial macrophages play a role in initiating and driving BCP
      induced inflammation. However, the molecular mechanisms by which BCP crystals
      exert their effects remain unclear. Here we demonstrate that exposure of
      macrophages to BCP crystals leads to activation of Syk and PI3 kinase.
      Furthermore, we show that production of pro-inflammatory cytokines and
      phosphorylation of the downstream kinase, ERK, are suppressed following treatment
      with Syk and PI3 kinase inhibitors. Finally, we demonstrate that treatment of
      macrophages with BCP crystals induces the production of the damage-associated
      molecule, S100A8, in a Syk dependent manner. We therefore identify Syk and PI3
      kinase as potential novel targets for the treatment of BCP-related pathologies.

PMID- 22854289
TI  - Ulcerative colitis presenting with Budd-Chiari syndrome.

PMID- 22854290
TI  - Psychotic reaction as a cardinal first clinical manifestation in a patient with
      Crohn's disease.

PMID- 22854291
TI  - Health related quality of life after radical cystectomy: comparative study
      between orthotopic sigmoid versus ileal neobladders.
AB  - AIMS: To comparatively assess the health-related quality of life (HRQOL) between
      patients with sigmoid and ileal neobladders (NBs) following radical cystectomy.
      METHODS: At out institution, the HRQOL of all patients with an orthotopic NB was
      evaluated using a Short-Form 36 (SF-36) survey 12 months after surgery. Of these,
      this study included 212 patients, consisting of 88 with sigmoid NB and 124 with
      ileal NB. RESULTS: There were no significant differences in all eight scores
      between sigmoid and ileal NB groups (SNBG and INBG, respectively); however, when
      compared with the scores in an age-matched control in Japan, one and two scores
      in SNBG and INBG, respectively, were significantly inferior, whereas one score in
      INBG was significantly favorable. Despite the lack of any significant differences
      in all scores between male SNBG and INBG, three scores in female SNBG were
      significantly superior to those in female INBG. Multivariate analyses were
      performed to evaluate the contribution of several factors on each scale score in
      the SF-36 survey, and they revealed that the age and voiding status had
      independent impacts on two and three scores, respectively, despite the lack of an
      independent association between any scores and the remaining factors, including
      the type of NB. CONCLUSIONS: The postoperative HRQOL of patients with NB was
      shown to be generally favorable irrespective of the type of NB; however, the
      HRQOL, particularly that associated with physical and social functions, appeared
      to be significantly impaired in elderly patients and/or those not able to
      spontaneously void.

PMID- 22854294
TI  - Measurement of children's physical activity using a pedometer with a built-in
      memory.
AB  - OBJECTIVES: We evaluated the accuracy of the Accusplit AH120 pedometer (built-in
      memory) for recording step counts of children during treadmill walking against
      (1) observer counted steps and (2) concurrently measured steps using the
      previously validated Yamax Digiwalker SW-700 pedometer. DESIGN: This was a cross
      sectional validation study performed under controlled settings. METHODS: Forty
      five 9-12-year-olds walked on treadmills at speeds of 42, 66 and 90m/min to
      simulate slow, moderate and fast walking wearing Accusplit and Yamax pedometers
      concurrently on their right hip. Observer counted steps were captured by video
      camera and manually counted. Absolute value of percent error was calculated for
      each comparison. Bland-Altman plots were constructed to show the distribution of
      the individual (criterion-comparison) scores around zero. RESULTS: Both
      pedometers under-recorded observer counted steps at all three walk speeds.
      Absolute value of percent error was highest at the slowest walk speed
      (Accusplit=46.9%; Yamax=44.1%) and lowest at the fastest walk speed
      (Accusplit=8.6%; Yamax=8.9%). Bland-Altman plots showed high agreement between
      the pedometers for all three walk speeds. CONCLUSIONS: Using pedometers with
      built-in memory capabilities eliminates the need for children to manually log
      step counts daily, potentially improving data accuracy and completeness. Step
      counts from the Accusplit (built-in memory) and Yamax (widely used) pedometers
      were comparable across all speeds, but their level of accuracy was dependent on
      walking pace. Pedometers should be used with caution in children as they
      significantly undercount steps, and this error is greatest at slower walk speeds.

PMID- 22854293
TI  - Prescription medication exchange patterns among methadone maintenance patients.
AB  - BACKGROUND: Exchange of prescription medications is a significant public health
      problem particularly among substance abusing populations. Little is known about
      the extent of medication sharing and receiving behaviors in methadone maintenance
      treatment (MMT) populations and the factors associated with such behaviors.
      METHODS: We examined rates, and factors associated with past year medication
      sharing and receiving practices of 315 MMT smokers who had enrolled in a clinical
      trial of smoking cessation. Sequential logistic regression models estimated the
      effect of demographic and substance use variables on the probability of sharing
      or receiving medications. RESULTS: Participants averaged 40 years of age, and 49%
      were male. Among persons prescribed medications, 19.9% reported sharing. Nearly
      40% had used medication not prescribed to them. Pain medications, sleep
      medications, and sedatives, were most commonly shared and received. Younger age
      was a significant predictor of both sharing medications (OR=0.92, 95%CI 0.88;
      0.96, p<.01) and receiving medications (OR=0.94, 95%CI 0.92; 0.97, p<.01).
      Financial hardship (OR=2.05, 95%CI 1.13; 3.72, p<.05), and recent use of heroin
      (OR=5.59, 95%CI 1.89; 16.57, p<.01) or cocaine (OR=3.70, 95%CI 1.48; 9.28,
      p<.05), were also independently associated with a significantly higher likelihood
      of receiving prescription drugs of abuse. CONCLUSIONS: The high prevalence of
      prescription medication sharing and receiving behaviors among persons in MMT
      often include substances with abuse potential and suggest the need for
      comprehensive approaches for minimizing this phenomenon.

PMID- 22854295
TI  - Drugs in sport: do we have what it takes to beat the battle?

PMID- 22854292
TI  - The genetics of alcohol dependence: advancing towards systems-based approaches.
AB  - BACKGROUND: Personalized treatment for psychopathologies, in particular
      alcoholism, is highly dependent upon our ability to identify patterns of genetic
      and environmental effects that influence a person's risk. Unfortunately, array
      based whole genome investigations into heritable factors that explain why one
      person becomes dependent upon alcohol and another does not, have indicated that
      alcohol's genetic architecture is highly complex. That said, uncovering and
      interpreting the missing heritability in alcohol genetics research has become all
      the more important, especially since the problem may extend to our inability to
      model the cumulative and combinatorial relationships between common and rare
      genetic variants. As numerous studies begin to illustrate the dependency of
      alcohol pharmacotherapies on an individual's genotype, the field is further
      challenged to identify new ways to transcend agnostic genomewide association
      approaches. We discuss insights from genetic studies of alcohol related diseases,
      as well as issues surrounding alcohol's genetic complexity and etiological
      heterogeneity. Finally, we describe the need for innovative systems-based
      approaches (systems genetics) that can provide additional statistical power that
      can enhance future gene-finding strategies and help to identify heretofore
      unrealized mechanisms that may provide new targets for prevention/treatments
      efforts. Emerging evidence from early studies suggest that systems genetics has
      the potential to organize our neurological, pharmacological, and genetic
      understanding of alcohol dependence into a biologically plausible framework that
      represents how perturbations across evolutionarily robust biological systems
      determine susceptibility to alcohol dependence.

PMID- 22854296
TI  - Finding the will and the way of ERAD substrate retrotranslocation.
AB  - ER-associated degradation (ERAD) is a mechanism by which numerous ER-localized
      proteins are targeted for cytosolic degradation by the ubiquitin-proteasome
      system. A surprising and still-cryptic requirement of this process is the energy
      dependent retrotranslocation of both lumenal and membrane-embedded ER proteins
      into the cytosol for ongoing ubiquitination and proteasomal destruction. The
      current understanding, results, and open questions are discussed below for this
      intriguing and critical process of ERAD.

PMID- 22854297
TI  - Logic structure of clinical judgment and its relation to medical and psychiatric
      semiology.
AB  - BACKGROUND: The logical nature of clinical judgment has been conceptualized in
      different ways, but a clear connection between the features of clinical judgment
      and those of semiology is still lacking. METHODS: The characteristics of clinical
      judgment, medical semiology, and psychiatric semiology are described. Connections
      between them are drawn. RESULTS: Clinical judgment is described as an abductive
      inference. Abductive inferences are especially useful to balance universal and
      singular information. In psychiatric semiology, due to some specific features, a
      careful balance between the information present in descriptive definitions and
      the information absent from the definition but present in singular symptoms is
      needed. The main types of out-of-definition information are reviewed.
      CONCLUSIONS: The implications of the results for diagnosis and research are
      drawn.

PMID- 22854298
TI  - Effects of multikinase inhibitors on pressure overload-induced right ventricular
      remodeling.
AB  - BACKGROUND: Little is known about the effects of current PAH therapies and
      receptor tyrosine kinase inhibitors on heart remodeling. We sought to investigate
      the effects of the multikinase inhibitors sunitinib (PDGFR-, VEGFR- and KIT
      inhibitor) and sorafenib (raf1/b-, VEGFR-, PDGFR-inhibitor) on pressure overload
      induced right ventricular (RV) remodeling. METHODS: We investigated the effects
      of the kinase inhibitors on hemodynamics and remodeling in rats subjected either
      to monocrotaline (MCT)-induced PH or to surgical pulmonary artery banding (PAB).
      MCT rats were treated from days 21 to 35 with either vehicle, sunitinib (1mg/kg,
      5mg/kg and 10mg/kg/day) or sorafenib (10mg/kg/day). PAB rats were treated with
      vehicle, sunitinib (10mg/kg/day) or sorafenib (10mg/kg/day) from days 7 to 21. RV
      function and remodeling were determined using echocardiography, invasive
      hemodynamic measurement and histomorphometry. RESULTS: Treatment with both
      sorafenib and sunitinib decreased right ventricular systolic pressure, pulmonary
      vascular remodeling, RV hypertrophy and fibrosis in MCT rats. This was associated
      with an improvement of RV function. Importantly, after PAB, both compounds
      reversed RV chamber and cellular hypertrophy, reduced RV interstitial and
      perivascular fibrosis, and improved RV function. CONCLUSION: We demonstrated that
      sunitinib and sorafenib reversed RV remodeling and significantly improved RV
      function measured via a range of invasive and non-invasive cardiopulmonary
      endpoints in experimental models of RV hypertrophy.

PMID- 22854299
TI  - Commentaries on viewpoint: sacrificing economy to improve running performance--a
      reality in the ultramarathon?

PMID- 22854300
TI  - Last word on viewpoint: sacrificing economy to improve running performance--a
      reality in the ultramarathon?

PMID- 22854301
TI  - Metabolic and ventilatory depression in rat.

PMID- 22854303
TI  - Pharmacological approaches to feeding behaviour and eating disorders.

PMID- 22854304
TI  - The psychobiology of comfort eating:  implications for neuropharmacological
      interventions.
AB  - Comfort eating, that is eating induced by negative affect, has been a core theme
      of explanations for overeating and obesity. Psychobiological explanations and
      processes underlying comfort eating are examined, as well as its prevalence in
      clinical and nonclinical populations, to consider who may be susceptible, whether
      certain foods are comforting, and what the implications for treatment may be.
      Comfort eating may occur in a substantial minority, particularly in women and the
      obese. Human and animal theories and models of emotional or stress-induced eating
      show some convergence, and may incorporate genetic predispositions such as
      impulsivity and reward sensitivity, associated with dopamine dysregulation
      underlying incentive salience. Comfort eaters show vulnerability to depression,
      emotional dysregulation and a need to escape negative affect and rumination.
      During negative affect, they preferentially consume sweet, fatty, energy-dense
      food, which may confer protection against stress, evidenced by suppression of the
      hypothalamic-pituitary-adrenal axis response, although activation of the
      hypothalamic-pituitary-adrenal axis may itself drive appetite for these palatable
      foods, and the risk of weight gain is increased. Benefits to mood may be
      transient, but perhaps sufficient to encourage repeated attempts to prolong mood
      improvement or distract from negative rumination. Cognitive behavioural
      treatments may be useful, but reliable drug therapy awaits further
      pharmacogenomic developments.

PMID- 22854305
TI  - Serotonin neurotransmission in anorexia nervosa.
AB  - Patients with anorexia nervosa (AN) show extreme dieting weight loss,
      hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5
      Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral
      changes observed in AN patients. Both genetic and environmental factors
      contribute toward the pathogenesis of AN. It is a frequent disorder among
      adolescent girls and young women and starts as an attempt to lose weight to look
      beautiful and attractive. Failure to see the turning point when fasting becomes
      unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin
      and an essential amino acid, is only available in the diet. It is therefore
      likely that excessive diet restriction and malnutrition decrease brain serotonin
      stores because the precursor is less available to the rate-limiting enzyme of 5
      HT biosynthesis, which normally exists unsaturated with its substrate. Evidence
      shows that diet restriction-induced exaggerated feedback control over 5-HT
      synthesis and the smaller availability of tryptophan decreases serotonin
      neurotransmission at postsynaptic sites, leading to hyperactivity, depression,
      and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A
      receptors and hypophagic serotonin receptors may be involved in anxiety and
      suppression of appetite. It is suggested that tryptophan supplementation may
      improve pharmacotherapy in AN.

PMID- 22854306
TI  - Dopamine in anorexia nervosa:  a systematic review.
AB  - Anorexia nervosa (AN) is a chronic relapsing psychiatric disorder with a largely
      unknown pathophysiology. Dopamine has been implicated in the pathophysiology of
      the disorder by preclinical and clinical evidence. Preclinical studies have
      examined two main characteristics of AN: reduction in food intake (diet
      restriction) and hyperactivity. Diet restriction has been associated with reduced
      dopamine levels in the hypothalamus, hippocampus, and the dorsal striatum. Animal
      hyperactivity following diet restriction has been linked to increased dopamine in
      the hypothalamus. Increased dopamine in the nucleus accumbens was associated with
      food administration, but not food expectation. Tyrosine and dopaminergic
      antagonists normalized anorexia-like behaviors in animal models of AN, but did
      not restore body weight. Clinical studies on the etiology of AN have produced
      contradictory findings. Cerebrospinal fluid concentrations of dopamine and its
      metabolites have been reported to be decreased or normal under conditions of low
      weight, whereas they tended to normalize when the weight was restored. Plasma and
      urinary levels of dopamine and its metabolites have been found to be normal,
      increased, and decreased. Neuroendocrine studies suggest that dopaminergic
      neurotransmission is increased in AN. However, recent neuroimaging studies lend
      support to the increase in binding of dopaminergic receptors in the striatum,
      which favors the opposite theory that intrasynaptic dopamine is indeed decreased.
      Genetic studies implicate dopamine D2 receptors, the dopamine transporter, and
      the enzyme COMT. There are promising results with respect to the use of atypical
      antipsychotics against symptoms of AN beyond weight gain, but further trials are
      required.

PMID- 22854307
TI  - Increased feeding and body weight gain in rats after acute and chronic activation
      of RXFP3 by relaxin-3 and receptor-selective peptides:  functional and
      therapeutic implications.
AB  - This paper provides a review of the effects of relaxin-3 and structurally related
      analogues on food intake and related behaviours, in relation to hypothalamic
      neural networks and chemical messengers known to control feeding, metabolism and
      body weight, including other neuropeptides and hormones. Soon after relaxin-3 was
      discovered, pharmacological studies identified the ability of the native peptide
      to stimulate feeding acutely in adult rats. Although interpretation of these data
      was confounded by ligand cross-reactivity at relaxin-family peptide (RXFP)
      receptors, studies with relaxin-3 analogues selective for the native relaxin-3
      receptor, RXFP3, confirmed that acute and chronic activation of RXFP3 increased
      feeding and weight gain, and produced changes in plasma leptin and insulin. These
      studies also identified the hypothalamus as a locus of action. Studies are now
      required to identify RXFP3-positive neuron populations involved in the effects of
      relaxin-3/RXFP3 signalling on metabolic and neuroendocrine homeostasis, and to
      determine whether peptide-based, nonpeptide-based or gene-based RXFP3 treatments
      can alter food intake and body weight in animal models of obesity and eating
      disorders, as a reflection of the therapeutic potential of this newly identified
      transmitter system.

PMID- 22854308
TI  - Effects of thiamine deficiency on food intake and body weight increment in adult
      female and growing rats.
AB  - The present study compared the effects of thiamine (vitamin B1) deficiency (TD)
      on the patterns of food intake and body weight in adult female and neonatal
      Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days
      either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine
      (210 B1). TD led to a marked reduction in food intake and the body weight set
      point, both recovering rapidly to their initial level in only 3 days after
      dietetic reversion. The effects of TD in developing rats were evaluated by
      subjecting pregnant rats to thiamine restriction during different time windows:
      prenatal (3 days before mating to parturition); perinatal (7 days after mating to
      the 10th postnatal day); and postnatal (from parturition to weaning). The effect
      of TD on the occurrence of low birth weight and ponderal growth retardation was
      examined from postnatal days 1 to 45. Only perinatal TD significantly decreased
      birth weight relative to untreated or pair-fed controls. Moreover, compared with
      the control treatments, ponderal growth retardation was not induced by prenatal
      TD, whereas induction of TD from perinatal into postnatal periods did cause
      ponderal growth retardation, with long-lasting effects persisting in adulthood.
      The results suggest a major physiological role of thiamine in the homeostasis of
      body weight programming, increment, and set point regulation in both offspring
      and adult female rats.

PMID- 22854310
TI  - Baclofen reduces binge eating in a double-blind, placebo-controlled, crossover
      study.
AB  - Baclofen has shown promise in treating substance use disorders and also reduced
      binge frequency in an open-label trial. This placebo-controlled, double-blind,
      crossover study further assessed the effects of baclofen on binge eating. Twelve
      individuals who self-reported binge eating completed the study. Data were
      collected during a run-in period (no drug or placebo), placebo phase (48 days),
      and baclofen phase (titrated up to 60 mg daily or the maximum tolerated dose, 48
      days). All the participants were exposed to all conditions. Participants
      completed a binge diary daily, and the Binge Eating Scale (BES), Food Craving
      Inventory-II (FCI-II), and Hospital Anxiety and Depression Scale (HADS) at
      regular intervals throughout the study. Baclofen significantly reduced binge
      frequency relative to placebo and run-in (P<0.05). This confirms results from the
      previous open-label trial. Baclofen also produced slight, but significant,
      increases in depression symptomatology as assessed by the HADS. Binge severity
      (BES scores) and craving (FCI-II scores) were significantly reduced during
      placebo and baclofen phases, that is both measures exhibited significant placebo
      effects. Tiredness, fatigue, and upset stomach were the most commonly reported
      side-effects. These results indicate that baclofen may be a useful treatment for
      binge eating in some patients.

PMID- 22854311
TI  - Emotional exhaustion as a predictor of tinnitus.

PMID- 22854309
TI  - Withdrawal from chronic, intermittent access to a highly palatable food induces
      depressive-like behavior in compulsive eating rats.
AB  - The increased availability of highly palatable foods is a major contributing
      factor toward the development of compulsive eating in obesity and eating
      disorders. It has been proposed that compulsive eating may develop as a form of
      self-medication to alleviate the negative emotional state associated with
      withdrawal from highly palatable foods. This study was aimed at determining
      whether withdrawal from chronic, intermittent access to a highly palatable food
      was responsible for the emergence of depressive-like behavior. For this purpose,
      a group of male Wistar rats was provided a regular chow diet 7 days a week
      (Chow/Chow), whereas a second group of rats was provided chow for 5 days a week,
      followed by a 2-day access to a highly palatable sucrose diet (Chow/Palatable).
      Following 7 weeks of diet alternation, depressive-like behavior was assessed
      during withdrawal from the highly palatable diet and following renewed access to
      it, using the forced swim test, the sucrose consumption test, and the
      intracranial self-stimulation threshold procedure. It was found that
      Chow/Palatable rats withdrawn from the highly palatable diet showed increased
      immobility time in the forced swim test and decreased sucrose intake in the
      sucrose consumption test compared with the control Chow/Chow rats. Interestingly,
      the increased immobility in the forced swim test was abolished by renewing access
      to the highly palatable diet. No changes were observed in the intracranial self
      stimulation threshold procedure. These results validate the hypothesis that
      withdrawal from highly palatable food is responsible for the emergence of
      depressive-like behavior, and they also show that compulsive eating relieves the
      withdrawal-induced negative emotional state.

PMID- 22854312
TI  - The clinical nurse educator as leader.
AB  - The National League for Nursing recognizes leadership as an important aspect of
      the educator role. The purpose of this article is to describe leadership in the
      context of clinical nursing education and how clinical nurse educators enact
      leadership. The article identifies particular nursing practice skills and
      strengths that clinicians bring to nursing education that enhance leadership
      knowledge, skills, and abilities. After review of several leadership models, we
      identified five overarching themes that demonstrate how clinical nurse educators
      exemplify the various models including role modeling, providing vision, helping
      students to learn, challenging the system or status quo, and seeking relational
      integrity. We explicate the themes with examples affirming the leadership
      potential of clinical nurse educators, and suggest ways in which nursing faculty
      members and administrators might draw on the leadership capital of clinical nurse
      educators.

PMID- 22854313
TI  - The role of reflective practices in enabling final year nursing students to
      respond to the distressing emotional challenges of nursing work.
AB  - Drawing on the findings of a phenomenological study which sought to understand
      something more about the lived experience of final year nursing students of
      learning through reflective processes; this paper seeks to consider how
      engagement with reflective practices enabled the participants to manage the
      distressing emotional challenges and labour of nursing work. Choosing to pay
      attention to the affective domain appeared to enable the participants to better
      understand the complex nature of the emotional challenges of nursing work and
      what it meant to them personally to be a nurse. Some of the participants were
      proud to describe how reflective activity had enabled them to develop and justify
      a 'traditional' emotional detachment from their care, whilst others used the 'own
      knowing' developed through reflective activity to reject the notion of
      professional detachment and come to value a more embodied sense of care which
      inevitably led them to become entangled in the distress and suffering of their
      patients. This type of personal reflective learning may emphasise and value more
      humanising characteristics of care.

PMID- 22854314
TI  - [Intraneural injection under ultrasound: what evidence].

PMID- 22854315
TI  - Stroke mimics treated with thrombolysis: further evidence on safety and
      distinctive clinical features.
AB  - BACKGROUND: Patients who present with symptoms mimicking ischaemic stroke (IS),
      but have a different diagnosis, are known as stroke mimics (SM). The necessity
      for rapid administration of intravenous thrombolysis in patients with acute IS
      may lead to treatment of patients with conditions mimicking stroke. A variable
      proportion of patients with SM (1.4-14%) are currently treated with intravenous
      tissue plasminogen activator therapy (IV-tPA). The outcome of these patients is
      generally favourable and complications are rather infrequent. We aimed to
      determine the frequency, clinical features and prognosis of SM patients treated
      with IV-tPA in an experienced stroke centre. METHODS: A prospective registry was
      assembled with patients treated with IV-tPA at our stroke unit from January 2004
      to December 2011. We recorded age, gender, baseline National Institutes of Health
      Stroke Scale (NIHSS) score, treatment delay, vascular risk factors, clinical
      syndrome and aetiology. We retrospectively analysed the clinical characteristics
      of SM, safety (symptomatic intracranial haemorrhage and mortality) and outcome
      measures (modified Rankin Scale at 3 months, mRS) and compared them with IS
      patients. RESULTS: 621 patients were treated with IV-tPA during the study period,
      606 (97.5%) were IS and 15 (2.4%) were SM. The aetiology of SM was somatoform
      disorders (5), headache and neurological deficits with cerebrospinal fluid
      lymphocytosis (HaNDL) syndrome (3), herpetic encephalitis (2), glial tumours (2),
      and migraine with aura, focal seizure and cortical vein thrombosis in single
      cases. SM were younger (72 +/- 14 vs. 53.7 +/- 16 years, p < 0.05), had a lower
      baseline deficit [NIHSS 13 (9-18) vs. 8 (5-10), p < 0.05], fewer vascular risk
      factors, and left hemisphere symptoms were predominant (80 vs. 52.4%, p < 0.05).
      Global aphasia without hemiparesis (GAWH) was the presenting symptom in 8 (54%)
      SM and 44 (7%) IS (p < 0.05). Multimodal computed tomography was performed in 3
      SM patients and showed perfusion deficits in 2 of them. No intracranial
      haemorrhage or disability (functional outcome at 3 months, mRS >2) was recorded
      in any SM patient. CONCLUSIONS: The use of intravenous thrombolysis appears to be
      safe in our SM patients, and prognosis is universally favourable. Somatoform
      disorder and HaNDL syndrome were prominent causes, and GAWH the most common
      presentation. The safety of thrombolysis in SM suggests that delaying or
      withholding treatment may be inappropriate: the benefit of thrombolysis in case
      of IS may outweigh the risks of treating an SM. Further studies may assess the
      future role of multimodal computed tomography in the differential diagnosis
      between IS and SM.

PMID- 22854316
TI  - Construction and characterization of an electrospun tubular scaffold for small
      diameter tissue-engineered vascular grafts: a scaffold membrane approach.
AB  - Based on a postulate that the microstructure of a scaffold can influence that of
      the resulting tissue and hence its mechanical behavior, we fabricated a small
      diameter tubular scaffold (~3 mm inner diameter) that has a microstructure
      similar to the arterial media using a scaffold membrane approach. Scaffold
      membranes that contain randomly oriented, moderately aligned, or highly aligned
      fibers were fabricated by collecting electrospun poly([epsilon]-caprolactone)
      fibers on a grounded rotating drum at three different drum rotation speeds (250,
      1000, and 1500 rpm). Membranes of each type were wrapped around a small-diameter
      mandrel to form the tubular scaffolds. Particularly, the tubular scaffolds with
      three different off-axis fiber angles (30, 45, and 60 degree) were formed using
      membranes that contain aligned fibers. These scaffolds were subjected to biaxial
      mechanical testing to examine the effects of fiber directions as well as the
      distribution of fiber orientations on their mechanical properties. The
      circumferential elastic modulus of the tubular scaffold was closely related to
      the fiber directions; the larger the off-axis fiber angle the greater the
      circumferential elastic modulus. The distribution of fiber orientations, on the
      other hand, manifested itself in the mechanical behavior via the Poisson effect.
      Similar to cell sheet-based vascular tissue engineering, tubular cell-seeded
      constructs were prepared by wrapping cell-seeded scaffold membranes, alleviating
      the difficulty associated with cell seeding in electrospun scaffolds. Histology
      of the construct illustrated that cells were aligned to the fiber directions in
      the construct, demonstrating the potential to control the microstructure of
      tissue-engineered vascular grafts using the electrospun scaffold membrane.

PMID- 22854317
TI  - Current clinical practice in postoperative endovascular aneurysm repair imaging
      surveillance.
AB  - PURPOSE: To investigate the current clinical practice in postoperative
      endovascular aneurysm repair (EVAR) imaging surveillance. MATERIALS AND METHODS:
      Corresponding authors of EVAR publications during the years 2006-2011 and
      subscribers to an endovascular journal were invited to complete a 27-question
      online survey related to institutional demographics, standard post-EVAR imaging
      surveillance, and imaging protocols in special circumstances (eg, renal
      insufficiency). RESULTS: The survey was completed by 515 of 9,631 physicians
      performing EVAR from 52 countries. Of respondents, 65.3% were affiliated with
      experienced centers where EVAR has been performed for > 10 years or with > 50
      EVAR procedures performed per year. Computed tomography (CT) angiography was the
      modality used most often for standard surveillance with a maximum time interval
      between studies of 12 months in 78.8% of centers out to 5 years. Experienced
      centers were more likely to delay follow-up imaging to 1 year after an
      unremarkable initial post-EVAR imaging study (P < .001), to extend surveillance
      intervals > 12 months (P = .043), and to use ultrasound (P < .01) for
      surveillance. After the detection of a type II endoleak, CT angiography was
      favored for follow-up by 59.4% of the respondents. Experienced centers were more
      likely to favor ultrasound (P = .006) and to schedule this follow-up examination
      later (after 6-12 months, P < .001). Of respondents, 62.8% used a glomerular
      filtration rate threshold of < 30 mL/min for not performing contrast-enhanced CT
      scan. In patients with renal insufficiency, most respondents performed ultrasound
      with or without a concomitant noncontrast CT scan. CONCLUSIONS: CT is the most
      frequently used method of long-term surveillance after EVAR. Use of ultrasound
      for long-term surveillance, extension of follow-up time intervals, or both were
      most often reported in experienced centers.

PMID- 22854318
TI  - Virtual reality simulation training in a high-fidelity procedure suite: operator
      appraisal.
AB  - PURPOSE: To assess the face and content validity of a novel, full physics, full
      procedural, virtual reality simulation housed in a hybrid procedure suite.
      METHODS AND MATERIALS: After completing 60 minutes of hands-on training in
      uterine artery embolization and coronary angioplasty, 24 radiologists and 18
      cardiologists with mean 10 years of endovascular experience assessed the
      functionality of a comprehensive hybrid procedure suite simulation (Orcamp;
      Orzone, Gothenburg, Sweden). RESULTS: C-arm and operating table functionality and
      realism were reliably (alpha = 0.0.89-0.92) rated highly (80/100). Performance
      realism of the catheter, guide wire, fluoroscopy image, electrocardiogram, and
      vital signs readout also reliably and statistically significantly predicted
      subjects' overall positive assessment (mean = 87/100) of the simulation
      experience in a multiple regression model (alpha = .83; r = 0.85 and r(2) = 0.67;
      P < .0001). CONCLUSIONS: This study reports a quantitative evaluation of a
      comprehensive simulation of an authentic procedure suite for image-guided
      intravascular procedures. This new facility affords the opportunity for trainers
      to provide higher fidelity training of operative technical, procedural, and
      management skills in the realistic context of a complete procedure suite with all
      its complexities and potential distractions.

PMID- 22854319
TI  - N-3 PUFAs have antiproliferative and apoptotic effects on human colorectal cancer
      stem-like cells in vitro.
AB  - The n-3 polyunsaturated fatty acids have been shown to inhibit the induction and
      progression of many kinds of tumor and to increase the therapeutic effects of
      numerous chemotherapeutics, but their anticancer effect on cancer stem cells from
      colorectal cancer has not been described previously. In the present study, we
      cultivated spheres from the SW620 cell line in serum-free medium and evaluated
      the features of the spheres by immunofluorescence, cell cycle distribution,
      resistance to chemotherapeutics and soft agar clone formation, and the spheres
      were shown to be cancer stem-like cells through tumorigenicity in athymic nude
      mice. Reverse transcriptase polymerase chain reaction analysis of pluripotency
      genes, such as Sox-2, Oct-4 and Bmi-1, showed that the spheres were generated by
      dedifferentiation of SW620 cells. The study explored the use of n-3
      polyunsaturated fatty acids (PUFAs) in spheres, which were treated with two n-3
      PUFAs [docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)]. Treatment of the
      spheres with DHA and EPA alone or in combination for 72 h led to apoptosis and
      the progressive loss of viability and DNA fragmentation and an increase in
      annexin V expression. DHA and EPA can enhance the chemotherapeutic sensitivity
      effect of 5-Fu and mitomycin C, especially DHA combined with EPA. Taken together,
      these results provide evidence that n-3 PUFAs exert a direct anticancer action
      that may contribute to their antiproliferative and proapoptotic effect on the
      cancer stem-like cells.

PMID- 22854320
TI  - Commentary: What measure of temperature is the best predictor of mortality?

PMID- 22854322
TI  - Ta1722, an anti-angiogenesis inhibitor targeted on VEGFR-2 against human
      hepatoma.
AB  - In order to investigate the anti-angiogenesis potential and related mechanisms of
      Ta1722 (a novel taspine derivative compound), a series of experiments in vivo and
      in vitro were carried out. The proliferation on human cell lines of SMMC-7721,
      A549, MCF-7, Lovo, and ECV304 was examined by MTT. Angiogenesis inhibition was
      examined by chick embryo chorioallantoic membrane (CAM) angiogenesis and tube
      formation assays. Related angiogenesis proteins and their mRNA expression were
      determined by western blotting and RT-PCR. In addition, the SMMC-7721 nude mouse
      xenotransplant model was used to evaluate the inhibition of tumor growth. The
      results showed that Ta1722 inhibited cell proliferation, angiogenesis of CAM and
      tube formation, and downregulated related positive angiogenesis proteins. The
      above indicated Ta1722 could serve as a promising candidate of angiogenesis
      inhibitors by interrupting the VEGF/VEGFR-2 pathway.

PMID- 22854321
TI  - Investigation of the association of growth rate in grower-finishing pigs with the
      quantification of Lawsonia intracellularis and porcine circovirus type 2.
AB  - As a part of a prospective cohort study in four herds, a nested case control
      study was carried out. Five slow growing pigs (cases) and five fast growing pigs
      (controls) out of 60 pigs were selected for euthanasia and laboratory examination
      at the end of the study in each herd. A total of 238 pigs, all approximately 12
      weeks old, were included in the study during the first week in the grower
      finisher barn. In each herd, approximately 60 pigs from four pens were
      individually ear tagged. The pigs were weighed at the beginning of the study and
      at the end of the 6-8 weeks observation period. Clinical data, blood and faecal
      samples were serially collected from the 60 selected piglets every second week in
      the observation period. In the killed pigs serum was examined for antibodies
      against Lawsonia intracellularis (LI) and procine circovirus type 2 (PCV2) and in
      addition PCV2 viral DNA content was quantified. In faeces the quantity of LI
      cells/g faeces and number of PCV2 copies/g faeces was measured by qPCR. The
      objective of the study was to examine if growth rate in grower-finishing pig is
      associated with the detection of LI and PCV2 infection or clinical data. This
      study has shown that diarrhoea is a significant risk factor for low growth rate
      and that one log(10) unit increase in LI load increases the odds ratio for a pig
      to have a low growth rate by 2.0 times. Gross lesions in the small intestine and
      LI load>log(10)6/g were significant risk factors for low growth. No association
      between PCV2 virus and low growth was found.

PMID- 22854323
TI  - Beneficial effects of high-dose atorvastatin pretreatment on renal function in
      patients with acute ST-segment elevation myocardial infarction undergoing
      emergency percutaneous coronary intervention.
AB  - OBJECTIVES: To investigate whether preprocedural high-dose atorvastatin decreases
      the incidence of contrast-induced nephropathy (CIN) and protects the renal
      function after emergency percutaneous coronary intervention (PCI). METHODS:
      Statin-naive patients with acute ST-segment elevation myocardial infarction
      (STEMI) undergoing emergency PCI (n = 161) randomly received atorvastatin (80 mg,
      n = 78, ATOR group) or placebo [n = 83, control (CON) group] followed by long
      term atorvastatin (40 mg/day). The primary end point was incidence of CIN.
      RESULTS: In the ATOR group, 2.6% of the patients developed CIN versus 15.7% in
      the CON group (p = 0.01). In the ATOR group, postprocedural serum creatinine was
      significantly lower (93.4 +/- 17.1 vs. 112.6 +/- 23.3 umol/l at 48 h and 84.2 +/-
      14.2 vs. 95.3 +/- 17.7 umol/l at 72 h, both p < 0.0001) and in the CON group,
      peak serum cystatin C was lower (0.51 +/- 0.14 vs. 0.61 +/- 0.13 mg/l, p <
      0.0001). Atorvastatin pretreatment was independently associated with a decreased
      risk of CIN (OR 0.084, 95% CI 0.015-0.462, p = 0.004). The proportion of alanine
      aminotransferase > 3 * upper limit of the normal value within 1 month was 3.85
      versus 1.20% (ATOR vs. CON group, p = 0.57). CONCLUSION: Preprocedural high-dose
      atorvastatin prevents CIN and protects the renal function in patients with acute
      STEMI undergoing emergency PCI.

PMID- 22854324
TI  - Current challenges and future achievements of blood transfusion service in
      Afghanistan.
AB  - Afghanistan is a country with population of over 28 million. The long term
      conflicts have devastated country's qualified resources including human
      resources. ANBSTS was established by MoPH as the country national blood service.
      Currently in addition to central and regional blood centers of ANBSTS many other
      hospitals have their own transfusion services. Blood donation in Afghanistan
      mainly depends on replacement donors. Donor selection and donor interview are not
      very efficient. Most of the blood in Afghanistan is administered as fresh whole
      blood. Although blood transfusion services in Afghanistan require more efforts to
      be fully efficient, based on recent improvements in working procedures of ANBSTS
      a promising future for blood transfusion services in Afghanistan is predicted.

PMID- 22854325
TI  - Blood donor satisfaction and the weak link in the chain of donation process.
AB  - Recruiting and retaining enough donors is a problem. Six hundred and thirty nine
      blood donors were interviewed to identify the elements that can influence their
      satisfaction and the decision to become regulars. The majority of them were
      satisfied with staff skill and communication, they declared they were calm before
      donating and felt well after donation. First-time donors (FTDs) were more
      frightened, showed anticipatory anxiety, were less sure they would donate again
      (p<0.01) and the youngest were also less satisfied with the staff's behavior
      after donation. Identifying the more scared FTDs and diminishing their anxiety
      before donating could positively influence their decision to become regulars.

PMID- 22854326
TI  - Treatment of recurrent hypoglycemia with plasmapheresis and steroid in
      nondiabetic patient.
AB  - We recently encountered a 35-year old man who suffered from frequent
      hypoglycemia. His blood test revealed the presence of high and suppressed level
      of insulin with supressed C-peptide levels, hypothalamic-pituitary axis was
      normal response in hypoglycemia and negative for anti-insulin antibody.
      Endocrinological and imaging data eliminated the possibility of insulinoma. His
      symptoms responded well to the therapy of prednisolone (60 mg/day) and
      plasmapheresis. We followed up the patient over the subsequent 6 months without
      remarkable lesions. He has had no further recurrences of hypoglycemia. We believe
      that the antiinsulin receptor antibody might have induced hypoglycemia in this
      patient.

PMID- 22854327
TI  - Total pubertal growth in patients with juvenile idiopathic arthritis treated with
      growth hormone: analysis of a single center.
AB  - OBJECTIVES: Growth failure is a permanent sequelae in juvenile idiopathic
      arthritis (JIA). The aim of the study was to compare pubertal growth in control
      and growth hormone (GH) treated JIA subjects. DESIGN: 64 children with JIA at a
      mean age of 10.38 +/- 2.80 years were enrolled and followed until final height
      (measured in standard deviation (SD) scores). 39 children (20 m) received GH
      therapy and 24 (9 m) served as controls. GH dose was 0.33 mg/kg/week. Linear
      regression analysis was performed to identify factors influencing total pubertal
      growth. RESULTS: Mean total pubertal growth was 21.1 +/- 1.3 cm (mean +/- SD) in
      GH treated JIA patients and 13.8 +/- 1.5 cm in controls. Final height was
      significantly higher with GH treatment (-1.67 +/- 1.20 SD) compared to controls (
      3.20 +/- 1.84 SD). Linear regression model identified age at onset of puberty
      (beta=-4.2,CI: -5.9, -2.6 in controls and beta=-2.3,CI: -3.6, -1.1 in GH treated)
      as the main factor for total pubertal growth. Final height SDS was determined by
      the difference to target height at onset of puberty (beta=-0.59;CI: -0.80, -0.37
      in controls and beta=-0.30,CI: -0.52, -0.08 in GH treated), age at onset of
      puberty (beta=0.47;CI:0.02,0.93 in controls and 0.23;CI: -0.00,0.46 in GH
      treated) and height gain during puberty (beta=0.13;CI:0.05,0.21 in controls and
      beta=0.11;CI:0.07,0.16 in GH treated). CONCLUSION: Total pubertal growth in JIA
      patients treated with GH was increased by a factor of 1.5 greater in comparison
      to controls leading to a significantly better final height. To maximize final
      height GH treatment should be initiated early to reduce the height deficit at
      onset of puberty.

PMID- 22854328
TI  - Variations in definitions of mortality have little influence on neonatal
      intensive care unit performance ratings.
AB  - OBJECTIVE: To measure the influence of varying mortality time frames on
      performance rankings among regional neonatal intensive care units (NICUs) in a
      large state. STUDY DESIGN: We performed a cross-sectional data analysis of very
      low birth weight infants receiving care at 24 level 3 NICUs. We tested the effect
      of 4 definitions of mortality: (1) death between admission and end of birth
      hospitalization or up to 366 days; (2) death between 12 hours of age and the end
      of birth hospitalization or up to 366 days; (3) death between admission and 28
      days; and (4) death between 12 hours of age and 28 days. NICUs were ranked by
      quantifying their deviation from risk-adjusted expected mortality and dividing
      them into 3 tiers: top 6, bottom 6, and in between. RESULTS: There was wide
      interinstitutional variation in risk-adjusted mortality for each definition
      (observed minus expected z-score range, -6.08 to 3.75). However, mortality-based
      NICU rankings and classification into performance tiers were very similar for all
      institutions in each of our time frames. Among all 4 definitions, NICU rank
      correlations were high (>0.91). Few NICUs changed relative to a neighboring tier
      with changes in definitions, and none changed by more than one tier. CONCLUSION:
      The time frame used to ascertain mortality had little effect on comparative NICU
      performance.

PMID- 22854329
TI  - Identification of physical abuse cases in hospitalized children: accuracy of
      International Classification of Diseases codes.
AB  - OBJECTIVE: Hospital discharge databases are being increasingly used to track the
      incidence of child physical abuse in the United States. These databases use
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM) codes to categorize illnesses and injuries in hospitalized patients.
      We assessed the accuracy of the assignment of these codes for cases of child
      physical abuse. STUDY DESIGN: Participants were all children (N = 133) evaluated
      by a child abuse pediatrician (CAP) for suspicion of abuse at Yale-New Haven
      Children's Hospital from January 1, 2007-December 31, 2010. These children
      included both those judged to have injuries from abuse and those judged to have
      injuries accidental/medical in nature. We compared the ICD-9-CM codes entered in
      the hospital discharge database for each child with the decisions made by the
      CAPs, as documented in their child abuse registry. The CAPs' decisions were
      considered to be the gold standard. Sensitivity and specificity were calculated.
      Medical records were reviewed for cases in which the ICD-9-CM codes disagreed
      with the CAP's decision. RESULTS: In 133 cases of suspected child physical abuse,
      the sensitivity and specificity of ICD-9-CM codes for abuse were 76.7 % (CI
      61.4%, 88.2%) and 100% (CI 96.0%, 100%), respectively. Analysis of the 10 cases
      of abuse not receiving ICD-9-CM codes for abuse revealed that errors in physician
      documentation (n = 5) and in coding (n = 5) contributed to the reduction in
      sensitivity. CONCLUSIONS: Despite high specificity in identifying child physical
      abuse, the sensitivity of ICD-9-CM codes is 77%, indicating that these codes
      underestimate the occurrence of abuse.

PMID- 22854330
TI  - Immunosensor based on magnetic relaxation switch and biotin-streptavidin system
      for the detection of Kanamycin in milk.
AB  - A rapid, sensitive, and simple immunosensor was developed for the detection of
      Kanamycin (KM) in milk. This immunosensor is based on magnetic relaxation switch
      (MRS) assay and biotin-streptavidin system (B-SA system). The target analyte (KM)
      competed with those on the surface of the superparamagnetic iron oxide (SPIO)
      nanoparticles and hence affected the formation of SPIO aggregates. The dispersed
      and aggregated states of SPIO can modulate the spin-spin relaxation time (T(2))
      of the neighboring water molecule. T(2) was then changed as an effect of the
      target analyte. The B-SA system was used to amplify the SPIO binding, thus
      enhance the sensitivity. The detection working was 1.5 to 25.2ng mL(-1) and limit
      of detection (LOD) was determined to be 0.1ng mL(-1). The LOD of the immunosensor
      decreased tenfold, and its analysis time (45min) was much shorter than that of
      enzyme-linked immunosorbent assay (6h to 8h). The average recoveries of the KM at
      various spiking levels ranged from 80.2% to 85.6% with a relative standard
      deviation (RSD) below 4.0%. The results showed that the MRS immunosensor was a
      promising platform for the determination of small molecular residues because of
      its high sensitivity, specificity, homogeneity, and speed.

PMID- 22854331
TI  - Vaccination with recombinant flagellar proteins FlgJ and FliN induce protection
      against Brucella abortus 544 infection in BALB/c mice.
AB  - Brucella has been considered as a non-motile, facultative intracellular
      pathogenic bacterium. However, the genome sequences of different Brucella species
      reveal the presence of the flagellar genes needed for the construction of a
      functional flagellum. Due to its roles in the interaction between pathogen and
      host, we hypothesized that some of the flagellar proteins might induce protective
      immune responses and these proteins will be good subunit vaccine candidates. This
      study was conducted to screening of protective antigens among these flagellar
      proteins. Firstly, according to the putative functional roles, a total of 30
      flagellar genes of Brucella abortus were selected for in vitro expression. 15 of
      these flagellar genes were successfully expressed as his-tagged recombinant
      proteins in Escherichia coli ER2566. Then, these proteins were purified and used
      to analyze their T cell immunity induction activity by an in vitro gamma
      interferon (IFN-gamma) assay. Five of the flagellar proteins could stimulate
      significantly higher levels of IFN-gamma secretion in splenocytes from S19
      immunized mice, indicating their T cell induction activity. Finally,
      immunogenicity and protection activity of these 5 flagellar proteins were
      evaluated in BALB/c mice. Results showed that immunization with FlgJ (BAB1_0260)
      or FliN (BAB2_0122) plus adjuvant could provide protection against B. abortus 544
      infection. Furthermore, mice immunized with FlgJ and FliN developed a vigorous
      immunoglobulin G response, and in vitro stimulation of their splenocytes with
      immunizing proteins induced the secretion of IFN-gamma. Altogether, these data
      suggest that flagellar proteins FlgJ and FliN are protective antigens that could
      produce humoral and cell-mediated responses in mice and candidates for use in
      future studies of vaccination against brucellosis.

PMID- 22854332
TI  - Diversity of antimicrobial resistance genes and class-1-integrons in
      phylogenetically related porcine and human Escherichia coli.
AB  - Antimicrobial resistant bacteria and resistance genes can be transferred between
      the microbial flora of humans and animals. To assess the dimension of this risk,
      we compared the phylogenetic ancestry of human and porcine tetracycline
      insusceptible Escherichia coli. Further, we compared the resistance gene profiles
      (tetA/tetB/tetC/tetD/tetM/sulI/sulII/sulIII/strA-strB/addA) and the prevalence of
      class-1-integrons in isolates of identical and different phylogroups by endpoint
      PCR. This is the first genotypic comparison of antimicrobial resistance in E.
      coli from humans and animals which allows for the phylogenetic ancestry of the
      isolates. E. coli isolates from diseased humans belonged regularly to phylogroup
      B2 (24.3%) or D (30.9%) and were rarely not typeable (7.2%); by contrast,
      isolates from pig manure were regularly not typeable (46.7%) and rarely grouped
      into phylogroup B2 (2.2%) or D (2.9%). Class-1-integrons were detected in 40.8%
      of clinical (n=152), in 9.5% of community-derived (n=21) and in 10.9% of porcine
      (n=137) E. coli. The prevalence of sulI (42.4%/16.0%) in phylogroup A and of
      tetA, tetB and sulII in phylogroup B1 differed significantly between human
      clinical and porcine strains. Human clinical isolates (except B2-isolates)
      carried significantly more different resistance genes per strain, compared to
      porcine or community-derived isolates. ERIC-PCR-analysis of B2- (and D-) isolates
      with identical genetic profiles revealed that only a minor part was clonally
      related. The dominant resistance gene profiles differed depending on phylogroup
      and source. Human and porcine isolates do not exceedingly share their genes, and
      might rapidly adapt their resistance gene equipment to meet the requirements of a
      new environment. The study underlines that resistance gene transfer between human
      and porcine isolates is limited, even in phylogenetically related isolates.

PMID- 22854333
TI  - Early neurological deterioration within 24 hours after intravenous rt-PA therapy
      for stroke patients: the Stroke Acute Management with Urgent Risk Factor
      Assessment and Improvement rt-PA Registry.
AB  - BACKGROUND: The initial 24 h after thrombolysis are critical for patients'
      conditions, and continuous neurological assessment and blood pressure measurement
      are required during this time. The goal of this study was to identify the
      clinical factors associated with early neurological deterioration (END) within 24
      h of stroke patients receiving intravenous recombinant tissue plasminogen
      activator (rt-PA) therapy and to clarify the effect of END on 3-month outcomes.
      METHODS: A retrospective, multicenter, observational study was conducted in 10
      stroke centers in Japan. A total of 566 consecutive stroke patients [211 women,
      72 +/- 12 years old, the median initial NIH Stroke Scale (NIHSS) score of 13]
      treated with intravenous rt-PA (0.6 mg/kg alteplase) was studied. END was defined
      as a 4-point or greater increase in the NIHSS score at 24 h from the NIHSS score
      just before thrombolysis. RESULTS: END was present in 56 patients (9.9%, 18
      women, 72 +/- 10 years old) and was independently associated with higher blood
      glucose [odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.07-1.28 per 1
      mmol/l increase, p < 0.001], lower initial NIHSS score (OR 0.92, 95% CI 0.87-0.97
      per 1-point increase, p = 0.002), and internal carotid artery (ICA) occlusion (OR
      5.36, 95% CI 2.60-11.09, p < 0.001) on multivariate analysis. Symptomatic
      intracranial hemorrhage within the initial 36 h from thrombolysis was more common
      in patients with END than in the other patients (per NINDS/Cochrane protocol, OR
      10.75, 95% CI 4.33-26.85, p < 0.001, and per SITS-MOST protocol, OR 12.90, 95% CI
      2.76-67.41, p = 0.002). At 3 months, no patients with END had a modified Rankin
      Scale (mRS) score of 0-1. END was independently associated with death and
      dependency (mRS 3-6, OR 20.44, 95% CI 6.96-76.93, p < 0.001), as well as death
      (OR 19.43, 95% CI 7.75-51.44, p < 0.001), at 3 months. CONCLUSIONS:
      Hyperglycemia, lower baseline NIHSS score, and ICA occlusion were independently
      associated with END after rt-PA therapy. END was independently associated with
      poor 3-month stroke outcome after rt-PA therapy.

PMID- 22854335
TI  - Management of hypotension associated with angiotensin-axis blockade and general
      anesthesia administration.

PMID- 22854334
TI  - Synergistic effect of neuroticism and body mass index on glucose metabolism in
      nondiabetic adults.

PMID- 22854336
TI  - Tranexamic acid reduces blood loss and financial cost in primary total hip and
      knee replacement surgery.
AB  - BACKGROUND: Blood conservation strategies have been developed to diminish blood
      transfusion requirements in patients undergoing hip or knee replacement surgery.
      Tranexamic acid (TA) is an inexpensive antifibrinolytic agent that is little used
      in orthopaedic surgery due to the absence of standardised optimal administration
      regimens. HYPOTHESIS: Blood transfusion requirements and induced costs can be
      diminished by using TA according to a standardised administration protocol in a
      large cohort of patients. MATERIALS AND METHODS: A retrospective study in
      patients who underwent joint replacement surgery by a single surgeon compared two
      periods, 2007-2008 without TA and 2008-2009 with TA. The 451 included patients
      underwent primary unilateral hip (n=261) or knee (n=190) replacement for
      osteoarthritis. Standardised protocols were used for surgery and anaesthesia. TA
      was given intravenously in a dose of 1g (i.e., 15mg/kg) at incision and wound
      closure then at 6-hour intervals for 24 hours. Blood losses were estimated using
      the Mercuriali formula. Haemoglobin on D -1 and D 8 and the number and volume of
      autologous (from intra-operative blood salvage) and homologous blood transfusions
      were collected. The costs of TA, blood salvage systems, and homologous blood
      units were recorded. The two groups were compared using Student's test,
      Wilcoxon's test, and the Khi(2) test, and multivariate analyses were performed.
      Values of p less than 0.05 were considered significant. RESULTS: TA use was
      associated with a significant decrease in the homologous blood transfusion rate
      (from 4% to 0%) and with 38% and 68% reductions in the rate and volume of
      autologous blood transfusions, respectively, due to a 34% decrease in blood
      losses. After taking into account the additional cost of TA therapy, there was a
      25% reduction in the cost of the blood conservation strategy. CONCLUSION: TA
      therapy abolished the need for homologous blood transfusion and induced no
      notable side effects. TA therapy decreased the amount of blood salvaged intra
      operatively, allowing a more rational use of the blood salvage system and
      decreasing the cost of anaesthesia. LEVEL OF EVIDENCE: IV. Retrospective case
      control.

PMID- 22854337
TI  - JBIR-137 and JBIR-138, new secondary metabolites from Aspergillus sp. fA75.

PMID- 22854338
TI  - Detection of the plasmid-mediated quinolone resistance determinants in clinical
      isolates of Serratia marcescens in China.

PMID- 22854339
TI  - Gilvocarcin HE: a new polyketide glycoside from Streptomyces sp.
AB  - A new antimicrobial polyketide glycoside (1) and three known compounds,
      gilvocarcins H (2), V (3) and M (4) were isolated from the ethyl acetate extract
      of Streptomyces sp. QD01-2. The structure of (1) was established by spectroscopic
      analysis, X-ray single crystal diffraction and CD spectra. The new compound (1)
      showed potent antimicrobial activities against Staphylococcus aureus, Bacillus
      subtilis, Escherichia coli and Candida albicans, with MIC values of 0.5-5.0 MUM.
      Compound (1) also showed weak cytotoxicity against the MCF-7, K562 and P388 cell
      lines, with IC(50) values of 36, 39 and 45 MUM, respectively. The results showed
      that the vinyl side chain helps to increase the cytotoxicity and antimicrobial
      activities of gilvocarcin-type glycosides. In addition, the NMR data of
      gilvocarcin H (2) were also reported for the first time.

PMID- 22854340
TI  - In vitro susceptibility of Staphylococcus aureus and Staphylococcus epidermidis
      isolated from prosthetic joint infections.
AB  - Prosthetic joint infections (PJI) are severe complications in Orthopedics, with
      Staphylococcus aureus and Staphylococcus epidermidis being the most commonly
      isolated pathogens. The variable antimicrobial susceptibility found in these
      microorganisms, along with the increasing number of methicillin-resistant
      strains, increases the difficulty of antibiotic selection and makes it necessary
      to perform individual susceptibility studies to select the optimal antibiotic
      treatment. The aim of this study was to evaluate the in vitro susceptibility
      pattern of 35 clinical strains isolated from PJI (17 S. aureus and 18 S.
      epidermidis) against rifampin, vancomycin, tygecicline, clindamycin,
      cotrimoxazole, cloxacillin, ciprofloxacin, daptomycin and fosfomycin. In vitro
      susceptibility assays were performed using the broth microdilution method and
      agar dilution for fosfomycin. MBC was also determined. Tygecicline and daptomycin
      showed the highest antimicrobial activity with low MIC(90) values, and no
      resistant strains were detected. On the other hand, ciprofloxacin and cloxacillin
      exhibited a poor antimicrobial effect with a high percentage of nonsusceptible
      strains in both species. Bactericidal activity rates revealed the bacteriostatic
      behavior of rifampin, tygecicline, cotrimoxazole, fosfomycin and clindamycin,
      whereas vancomycin and cloxacillin showed species- and strain-dependent behavior.
      Daptomycin and ciprofloxacin were observed to be efficient bactericidal agents
      against the tested strains. According to our data, rifampin, tigecycline,
      daptomycin and fosfomycin showed high in vitro activity against most
      staphylococcal strains isolated from the PJIs tested, although daptomycin seems
      to be the best alternative to vancomycin therapy.

PMID- 22854341
TI  - An integrated analysis of liver safety data from orlistat clinical trials.
AB  - OBJECTIVE: Orlistat is an oral gastrointestinal lipase inhibitor and is indicated
      for treatment of obesity in combination with a hypocaloric diet. Post-marketing
      reports of adverse reactions revealed hints for possible drug-induced liver
      injury which has prompted changes to the product information. Orlistat's
      development program, involving over 30,000 patients, did not indicate a hepatic
      safety issue. METHODS: We analyzed liver function test data from randomized
      clinical trials of orlistat, using i) meta-analysis of published study safety
      data, ii) time-to-event analysis for individual patients, and iii) a novel and
      more sensitive method derived from the U.S. Food and Drug Administration's (FDA)
      evaluation of drug-induced serious hepatotoxicity (eDISH) technique. Over 10,000
      subjects were included. RESULTS: The combined odds ratio from a simple summary
      level fixed-effects meta-analysis of treatment-emergent abnormalities in serum
      alanine aminotransferase (ALT) (defined as greater than the upper level of normal
      for 2 successive measurements) was 1.09 (95% CI 0.93-1.28), and in total
      bilirubin 1.24 (95% CI 1.03-1.49). Part of the small apparent effect was due to
      longer exposure to orlistat than to placebo, on average. A patient-level display,
      adjusting for regression towards the mean, and Kaplan-Meier analysis of changes
      in ALT and bilirubin, taking account of different exposure, showed no significant
      difference between orlistat and placebo. This shows that there is no signal for
      hepatic damage in clinical studies of orlistat. CONCLUSION: While idiosyncratic
      liver injury following exposure to orlistat cannot be excluded, it is likely to
      be extremely rare.

PMID- 22854342
TI  - Excellent fixation achieved with cementless posteriorly stabilized total knee
      arthroplasty.
AB  - Cementless posteriorly stabilized (PS) total knee arthroplasty has not been
      widely accepted primarily because of prior unpredictable results and concern
      about micromotion at the tibial fixation interface caused by the cam/post
      interaction. A prospective consecutive series of 114 cementless, tricompartmental
      periapatite-coated single-radius PS implants in 110 patients with a mean age 62
      years was performed to determine if initial stability and biologic fixation could
      be achieved. At a mean follow-up of 36 months, all implants demonstrated
      radiographic evidence of stable biologic fixation with no evidence of loosening,
      osteolysis, stress shielding, or progressive radiolucent lines. Based on these
      early results, cementless, periapatite-coated single-radius PS total knee
      arthroplasty offers marked promise.

PMID- 22854343
TI  - Re: Dislocation after total hip arthroplasty: a randomized clinical trial of a
      posterior approach and a modified lateral approach. J Arthroplasty
      2012;27(3):378.

PMID- 22854344
TI  - A long-term survivorship comparison between cemented and uncemented cups with
      shelf grafts in revision total hip arthroplasty after dysplasia.
AB  - Long-term outcomes of cemented and uncemented cups were compared in patients with
      hip dysplasia who had undergone revision hip arthroplasty. Patients had
      uncontained superolateral acetabular defects reconstructed with a structural
      allograft. This retrospective study compared 18 cemented acetabular cups to 27
      uncemented acetabular cups. Average follow-up was 216 months (range, 96-312).
      Nineteen acetabular cups (42%) failed due to loosening and were revised. The 10-
      and 20-year cup survival was 88% and 76% in the uncemented group and 67% and 36%
      in the cemented group. Log rank analysis showed this difference to be significant
      (P = .0077). Uncemented acetabular cups performed significantly better than
      cemented cups.

PMID- 22854345
TI  - Comparison of high tibial osteotomy and unicompartmental knee arthroplasty at a
      minimum follow-up of 3 years.
AB  - The purpose of this study was to compare clinical outcomes including return to
      recreational activities (cycling, swimming, exercise walking, dancing, jogging,
      and mountain climbing) after opening-wedge high tibial osteotomy (HTO) and
      unicompartmental knee arthroplasty (UKA). Clinical outcomes were assessed using
      Tegner activity scores, ranges of motion, and Lysholm knee scores. In both
      groups, the number of patients participating in recreational activities was
      significantly reduced after surgery, but without a significant intergroup
      difference (1.3 activities in HTO group and in 1.6 activities in UKA group).
      Average Tegner activity scale scores, ranges of motion, and Lysholm knee scores
      did not show significant differences between the 2 groups. This study identified
      no significant differences between HTO and UKA for medial unicompartmental
      osteoarthritis in terms of return to recreational activity and short-term
      clinical outcomes.

PMID- 22854346
TI  - Intermediate- to long-term results after hybrid total hip arthroplasty in
      patients with rheumatoid arthritis.
AB  - There have been few reports describing intermediate- to long-term results after
      hybrid total hip arthroplasty in patients with rheumatoid arthritis. We followed
      up 52 hips in 44 patients aged 5 men and 39 women, with a mean of 11.5 years
      (range, 5-23.5 years). Revisions had been performed in 6 hips in 6 patients: 1
      both acetabular and femoral components for infection, 1 acetabular component for
      aseptic loosening, 3 acetabular components for recurrent dislocation, and 1
      acetabular component for dislodgement of the polyethylene liner from the metal
      shell. None of other acetabular or femoral components were revised or found to be
      loose at the final follow-up. Although postoperative dislocation remains a
      concern, hybrid total hip arthroplasty had an acceptable result in patients with
      rheumatoid arthritis.

PMID- 22854347
TI  - Acetabular alignment and primary arc of motion for minus, skirtless, and skirted
      28-, 32-, 36-, and 40-mm femoral heads.
AB  - We examined the influence of acetabular cup alignment on the primary arc of
      motion (PAOM) for minus (-3.5), skirtless (+3.5), and skirted (+10.5) neck
      lengths with 28-, 32-, 36-, and 40-mm femoral heads. Total hip arthroplasty was
      performed in a pelvic saw bone model. The acetabulum was positioned in 30 degrees
      /45 degrees /60 degrees  abduction and 0 degrees /15 degrees /30 degrees 
      anteversion, respectively. The PAOM was determined using a digital inclinometer
      for each of the acetabular positions and 12 femoral heads mentioned above. Best
      PAOM was found in 45 degrees  abduction and 15 degrees  to 30 degrees 
      anteversion as well as 60 degrees  abduction and 0 degrees  anteversion.
      Combinations of excessive abduction and anteversion as well as horizontalization
      and retroversion resulted in the worst PAOM. Primary arc of motion is mainly
      determined by cup alignment even when using larger femoral heads.

PMID- 22854348
TI  - Re: Hip resurfacing arthroplasty in inflammatory arthritis (vol 27-1,15-20;
      2012).

PMID- 22854349
TI  - Delayed sciatic nerve injury by posterior flange of reinforcement ring after
      acetabular revision surgery.
AB  - Delayed onset of sciatic neuropathy after total hip arthroplasty is uncommon, and
      late hardware-induced sciatic nerve complications are rarely reported. Here, we
      report a patient in whom the posterior flange of the reinforcement ring caused
      severe late sciatic nerve injury. Sciatic nerve radiography was useful for
      diagnosing flange-related sciatic nerve injury.

PMID- 22854350
TI  - Acetabular cup stiffness and implant orientation change acetabular loading
      patterns.
AB  - Acetabular cup orientation has been shown to influence dislocation, impingement,
      edge loading, contact stress, and polyethylene wear in total hip arthroplasty.
      Acetabular implant stiffness has been suggested as a factor in pelvic stress
      shielding and osseous integration. This study was designed to examine the
      combined effects of acetabular cup orientation and stiffness and on pelvic
      osseous loading. Four implant designs of varying stiffness were implanted into a
      composite hemipelvis in 35 degrees  or 50 degrees  of abduction. Specimens were
      dynamically loaded to simulate gait and pelvic strains were quantified with a
      grid of rosette strain gages and digital image correlation techniques. Changes in
      the joint reaction force orientation significantly altered mean acetabular bone
      strain values up to 67%. Increased cup abduction resulted in a 12% increase along
      the medial acetabular wall and an 18% decrease in strain in inferior lateral
      regions. Imbalanced loading distributions were observed with the stiffer
      components, resulting in higher, more variable, and localized surface strains.
      This study illustrates the effects of cup stiffness, gait, and implant
      orientation on loading distributions across the implanted pelvis.

PMID- 22854351
TI  - Accuracy of digital preoperative templating in 100 consecutive uncemented total
      hip arthroplasties: a single surgeon series.
AB  - Digital templating is an accurate method of assessing femoral and acetabular
      component sizes. This allows surgeons to foresee potential problems and also
      recognize an intraoperative error when a large discrepancy exists between a trial
      component and the templated size. Preoperative templating data of pelvic
      radiographs from 100 consecutive patients receiving uncemented implants were
      templated with Orthoview software (version 2.0CEN; Meridian Technique Ltd,
      Southampton, United Kingdom). Seventy-five percent of stems were templated to
      within 0.5 size, and 98%, to within 1 size. Eighty percent of cups were templated
      to within 2 mm, and 98%, to within 4 mm, and 62% of head length was accurately
      template. Seven patients were converted from a templated 132 degrees  to a 127
      degrees  femoral prosthesis neck angle. The mean lower limb length discrepancy
      was +0.05 mm (SD, 5.1 mm) postoperatively.

PMID- 22854352
TI  - Prooxidant-antioxidant balance and antioxidized LDL antibody level values and
      cardiac function in patients with coronary artery disease.
AB  - OBJECTIVES: We studied the association between the prooxidant-antioxidant balance
      (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox
      LDL) IgG antibody and indices of cardiac function (systolic and diastolic
      function) in patients with coronary artery disease (CAD). METHODS: Fifty-five
      patients with established CAD were selected, and serum levels of anti-ox-LDL IgG
      and PAB values were measured and compared with 40 matched healthy controls.
      Systolic and diastolic functions were determined for all patients. RESULTS: PAB
      values were significantly higher in patients than in controls (p < 0.001), whilst
      serum anti-ox-LDL concentrations were not statistically different between the 2
      groups (p = 0.821). However, after adjustment for high-density lipoprotein
      cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB
      values were inversely associated with ejection fraction (r = -0.326, p = 0.031),
      but this was not the case for anti-ox-LDL in either group (p > 0.05). CONCLUSION:
      Serum concentrations of a marker of oxidative stress (PAB values) are inversely
      associated with cardiac function. PAB is a relatively simple index that could be
      incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody
      concentration does not appear to reflect total oxidative stress as assessed by
      PAB.

PMID- 22854353
TI  - Microbial contamination of a disinfectant-soaked unwoven cleaning cloth.
AB  - In December 2009, a 76-year-old male patient developed pneumonia due to
      Burkholderia cepacia whilst in an intensive care unit at a Japanese university
      hospital. During the subsequent environmental investigation to find the source,
      B. cepacia with an identical DNA type was found in his denture storage solution.
      Open packets of unwoven rayon cloths soaked in 0.2% alkyldiaminoethylglycine
      hydrochloride, used for environmental cleaning, were shown to be contaminated
      with B. cepacia, Alcaligenes xylosoxidans, Pseudomonas fluorescens and
      Pseudomonas aeruginosa. B. cepacia of a different DNA type was found in five of
      42 samples from sealed packets of cloths.

PMID- 22854355
TI  - Prevalence of high-level mupirocin resistance among meticillin-resistant
      Staphylococcus aureus isolates in a tertiary care hospital in Singapore.
AB  - High-level resistance to mupirocin in meticillin-resistant Staphylococcus aureus
      (MRSA) jeopardizes its role in nasal decolonization protocols. We carried out a
      study in 2010 to determine the prevalence of high-level mupirocin resistance in
      our tertiary-care hospital. The prevalence of high-level resistance to mupirocin
      in MRSA in this hospital was 11%. There was also complete agreement between the
      genotypic and phenotypic methods of detection of high-level mupirocin resistance
      in 24 of the screening isolates.

PMID- 22854356
TI  - Beyond equity of access to equity of outcome.

PMID- 22854354
TI  - Legionella pneumophila serogroup 1 in a birthing pool.
AB  - This report describes a risk assessment and subsequent actions following
      isolation of Legionella pneumophila serogroup 1 in the water supply to a birthing
      pool during a planned maintenance programme. A literature search for cases of
      neonatal legionellosis identified 24 reports of cases among babies aged <2
      months, two of which were associated with water births. On this basis, the pool
      was closed until Legionella spp. were undetectable. Control proved difficult as
      hyperchlorination failed, and a filter fitted to the thermostatic mixer tap
      supplying the pool slowed filling so much that additional taps were required to
      achieve a satisfactory flow rate.

PMID- 22854357
TI  - The use of troponin testing in primary care.

PMID- 22854359
TI  - The use of troponin in general practice.
AB  - BACKGROUND: General practitioners are able to measure cardiac troponin in order
      to help triage patients with symptoms suspicious of acute coronary syndrome. The
      aim of this study was to assess the utilisation of cardiac troponin testing in
      the community. METHODS: An audit of all cardiac troponin testing in an urban
      community from a single laboratory in 2010 was performed. Data regarding
      admissions and adverse events over a 6-month period was carried out in all
      patients. RESULTS: Cardiac troponin was measured during 2662 patient events
      during 2010. There were 223 patients episodes (8.4%) in which greater than and
      equal to 1 troponin result was elevated, 184 (82.5%) were admitted to hospital,
      101 (54.9%) were diagnosed as acute coronary syndrome. Of the 2439 with normal
      troponin results, 344 (14.1%) were admitted, 42 (12.2%) were diagnosed as acute
      coronary syndrome. Only 12.1% had serial troponin measurements. The 6-month rates
      of death were 8.5% versus 1.1%, myocardial infarction were 2.2% versus 1.2%,
      revascularisation were 1.8% versus 0.7%, heart failure were 3.1% versus 1.0% in
      those with elevated versus normal troponin respectively. CONCLUSION: The use of
      troponin in the community appropriately triages patients regarding the need for
      admission. However, many patients had elevated troponin due to non-coronary
      causes. The indication for testing only in cases of suspected ACS and the use of
      serial cTn measurement in early presenters should be emphasised.

PMID- 22854358
TI  - The most deprived Auckland City Hospital patients (2005-2009) are 10 years
      younger and have a 50% increased mortality following discharge from a cardiac or
      vascular admission when compared to the least deprived patients.
AB  - AIM: To examine how socioeconomic deprivation affects medium to long-term patient
      outcomes following hospital discharge for a cardiac or vascular admission.
      METHODS: We performed a retrospective analysis of all patients aged >15 years of
      age discharged from Auckland City Hospital between 1/7/2005 and 31/12/2009 with a
      cardiac or vascular diagnostic-related group (DRG) using prospectively collected
      data from their Auckland District Health Board (ADHB) discharge, including their
      'deprivation index', a small area marker of socioeconomic deprivation graded as 1
      (the least deprived) to 10 (the most deprived). We then matched these data with
      the ADHB admissions patient data (for subsequent readmissions) and with the
      National death registry. RESULTS: In these 4.5 years, 252,974 patients, resident
      in the ADHB region, were discharged from the ADHB, of whom 19,545 patients had
      presented with a cardiac or vascular DRG. Of these, 3,609 (18%) patients [mean
      age 66 (SD18) years] with a deprivation index of 1 or 2 were classified as 'least
      deprived', with 3812 (20%) patients [mean age 57 (SD19) years] with a deprivation
      index of 9 or 10 being classified as 'most deprived'. The most deprived patients
      were, on average, 10 years younger (P<0.0001). 344 [1.8% (95%CI 1.6-1.9)]
      patients died in hospital and 2970 [15.2% (95%CI 14.8-15.6)] died within a mean
      follow-up of 2.5 (SD1.4) years. Compared with those least deprived (NZDep Index
      2006 1-2) the age and gender adjusted risk of death in the most deprived (NZDep
      Index 2006 9-10) at median 2.4 years after discharge, was increased by 50% [OR
      1.5 (95%CI 1.3-1.7) P<0.0001]. CONCLUSIONS: Following discharge after a cardiac
      or vascular related admission and after adjusting for imbalance in age and
      gender, and also in models with adjustment for age, gender and ethnicity,
      socioeconomic deprivation was associated with an increased chance of death and
      hospitalisation following discharge. Despite programmes to minimise health
      disparities, comprehensive strategies to improve on this health inequality are
      still needed within the New Zealand health care environment.

PMID- 22854360
TI  - Availability of troponin testing for cardiac patients in New Zealand 2002 to
      2011: implications for patient care.
AB  - AIMS: For patients presenting with an acute coronary syndrome (ACS), troponin T
      or I levels are crucial for the diagnosis of myocardial infarction (MI). We
      investigated troponin tests, analyser types and thresholds used in New Zealand
      (NZ) from 2002 to 2011. METHODS: We reviewed troponin tests available at
      hospitals in NZ which admitted ACS patients and those who had troponin testing in
      2002 (n=41), 2007 (n=43) and 2011 (n=43). We also contacted community
      laboratories and manufacturers. RESULTS: In 2010-11 there were nine different
      troponin analysers in 43 hospitals provided by five companies. Troponin T assays
      were used in 58% of the hospitals and 42% used troponin I as their first-line
      method. Quoted cutpoints have become more aligned since 2002 and 2007, but are
      still different from laboratory cutpoints using point of care methods.
      CONCLUSIONS: There are differences in troponin tests available across NZ. Test
      thresholds and units vary, even for the same test, and available diagnostic
      information cannot always be used to identify a troponin rise and fall. Care is
      needed when comparing results from different methods and when point of care
      instruments are used. A coordinated national approach to the development of new
      biochemical tests, such as troponins, may result in better use of resources and
      better patient care.

PMID- 22854361
TI  - Mortality by ethnic group to 2006: is extending census-mortality linkage robust?
AB  - OBJECTIVE: To update trends in mortality by ethnic group from the New Zealand
      Census-Mortality Study (NZCMS), by additionally linking 2004-06 mortality records
      to the 2001 Census. To investigate possible bias from this extended linkage,
      especially for Pacific and Asian people who emigrate more frequently. METHODS:
      Anonymous and probabilistic record linkage of 2004-06 mortality records with the
      2001 Census was undertaken. Age-standardised 1-74 year old mortality rates by sex
      and age group, and for all-cause and selected causes of death, were calculated
      using the direct method for first 30 months post 2001 Census (2001-03) and second
      30 months (2003-06). RESULTS: Observed all-cause mortality rates continued to
      fall in 2003-06 compared to previous periods, but more so for Pacific (18.3% and
      21.7% for males and females for 2003-06 compared to 2001-04, respectively) and
      Asian (22.2%, 16.7%), than for Maori (13.2%, 14.2%) and European/Other (13.0%,
      10.4%). Observed rate ratios for Maori, compared to European/Other were 2.43 (95%
      CI 2.31-2.57) for males and 2.72 (2.56-2.89) for females, the same (males) and
      slightly less (7%, females) than in 2001-03. Declines in cardiovascular disease
      (CVD) and injury mortality were the main drivers of all-cause mortality rate
      reductions for all ethnic groups. Relative inequalities in CVD between Maori and
      European/Other remain high (three to four-fold relative risks), but reduced by 8%
      for both males and females from 2001-03 to 2003-06, which in turn means that
      absolute inequalities closed by as much as 20%. CONCLUSION: We suspect that
      analyses comparing mortality rates over time within one of the closed NZCMS
      cohorts (e.g. 2001-03 compared to 2003-06) is prone to bias due to our inability
      to censor people when they migrate out of New Zealand. This limitation means
      mortality rates in the NZCMS are increasingly underestimated with time since
      census night, particularly for Pacific and Asian people. However, previously
      published NZCMS trends remain valid as the duration of follow-up (3 years) is
      short, and cohorts were not split by time since census. Nevertheless, it is safe
      to conclude that mortality rates continued to decline from 2001-03 to 2003-04 for
      all four ethnic groups. All-cause mortality inequalities for Maori compared to
      European/Other over this time were probably stable in relative terms and
      decreasing in absolute terms, but cardiovascular disease (CVD) inequalities
      probably decreased in both absolute and relative terms.

PMID- 22854362
TI  - Improving healthcare through the use of co-design.
AB  - AIM: This paper describes how co-design methods can be used to improve patient
      experiences and services within healthcare organisations. Using the Patient Co
      design of Breast Service Project as an example, we describe how patient
      experiences were captured and understood, the improvements made and implications
      for future work. METHOD: We used a six-step process: engage, plan, explore,
      develop, decide and change. Tools and techniques employed were based on service
      design approaches. These included patient journey mapping, experience-based
      surveys and co-design workshops. RESULTS: Information, communication, navigation
      and co-ordination, and environment emerged as key themes for the Breast Service.
      And as a result, a suite of improvements were made. Key methodological learnings
      included using co-design alongside traditional quality improvement methodologies,
      engaging with patients early, the importance of staff buy-in and the necessity of
      trying things outside one's comfort zone. CONCLUSION: Use of co-design within the
      Breast Service has resulted in tangible improvements and has demonstrated the
      value of engaging patients and focussing on their experiences. It is recommended
      that: evaluation phases are factored into future co-design work, further research
      is conducted on sustainability and funding and support is given to allow co
      design to become more widespread throughout New Zealand.

PMID- 22854363
TI  - Doctors and the nurse endoscopist issue in New Zealand.
AB  - AIM: Training and recruitment of Nurse Endoscopists (NEs) is currently actively
      debated in medical circles. The aim of this survey was to obtain the views of
      doctors regarding the role of NEs in New Zealand (NZ). METHODS: A web-based, self
      administered questionnaire was sent to 84 endoscopists currently working in 25
      public hospitals across all the 20 District Health Boards. The survey period was
      July 2011. Data was analysed using descriptive statistics. RESULTS: The response
      rate was 47.5%. Fifty percent of the respondents worked in tertiary hospitals.
      Only 30% had a positive attitude towards the introduction of NEs in NZ. The
      majority (62%) believed that doctors would deliver better quality of endoscopy
      services than NEs. Only 37% thought that the introduction of NEs will reduce the
      cost of services. Forty-one percent thought it was inappropriate for the NEs to
      be enrolled in the Bowel Cancer Screening Programme and only 6 doctors (18%)
      thought that NEs should be allowed to perform therapeutic endoscopic procedures.
      CONCLUSION: Only a minority of doctors had a positive attitude towards the role
      of NEs. The majority considered doctors to deliver 'higher' quality of service
      and only a minority thought that the introduction of NEs will lower the cost of
      services.

PMID- 22854364
TI  - Establishment of the New Zealand Drivers Study.
AB  - AIM: Despite a significant improvement since graduated licensing was introduced,
      traffic related injury remains the leading cause of death and hospitalisation
      among young New Zealanders. The New Zealand Drivers Study (NZDS) was established
      with a view to providing information that would lead to an improvement in this
      situation. The NZDS is a prospective cohort study designed to explore the
      relationship between a comprehensive range of driving and traffic safety related
      factors and subsequent traffic crashes and convictions among newly licensed
      drivers. We describe key process objectives in establishing the cohort, and our
      success in meeting them and the implications arising thereof. METHODS: We compare
      what occurred with what was proposed in the research protocol. RESULTS: We
      successfully established a cohort of 3992 newly licensed car drivers with
      substantial heterogenity in sociodemographic, behavioural, and driving
      experiences. We have 825 Maori that will allow us to undertake a separate Maori
      analyses. Response rates to interviews at the restricted and full licence stages
      have been very high at 87% and 93%, respectively. We have been successful via
      linkage in following them through the stages of licensure and via linkage
      obtaining national data on the outcomes of interest. CONCLUSIONS: The NZDS is
      well placed to make a significant contribution to our knowledge of young driver
      road safety behaviour. This process has already commenced.

PMID- 22854365
TI  - Christchurch earthquakes: how did former refugees cope?
AB  - AIM: This study investigated how former refugees now living in Christchurch
      (Canterbury Province, New Zealand) communities coped after the 4 September 2010
      and subsequent earthquakes. METHOD: A systematic sample of one in three former
      refugees from five ethnic groupings (Afghanistan, Kurdistan, Ethiopia, Somalia
      and Bhutan) was selected from a list of 317 refugees provided by the Canterbury
      Refugee Council and invited to participate in the study. Seventy-two out of 105
      potential participants completed a 26 item questionnaire regarding the impact of
      the quakes, their concerns and anxieties, coping strategies and social supports.
      The methodology was complicated by ongoing aftershocks, particularly that of 22
      February 2011. RESULTS: Three-quarters of participants reported that they had
      coped well, spirituality and religious practice being an important support for
      many, despite less then 20% receiving support from mainstream agencies. Most
      participants (72%) had not experienced a traumatic event or natural disaster
      before. Older participants and married couples with children were more likely to
      worry about the earthquakes and their impact than single individuals. There was a
      significant difference in the level of anxiety between males and females. Those
      who completed the questionnaire after the 22 February 2011 quake were more
      worried overall than those interviewed before this. CONCLUSION: Overall, the
      former refugees reported they had coped well despite most of them not
      experiencing an earthquake before and few receiving support from statutory relief
      agencies. More engagement from local services is needed in order to build trust
      and cooperation between the refugee and local communities.

PMID- 22854366
TI  - New Zealand 2012 guidelines for the management of non ST-elevation acute coronary
      syndromes.

PMID- 22854367
TI  - Dabigatran: rational dose individualisation and monitoring guidance is needed.
AB  - Dabigatran is the first oral anticoagulant to be introduced in New Zealand
      without prescribing restrictions for over 50 years. Not surprisingly, the drug
      has created a great deal of interest amongst health care providers as well as the
      general public and media. There seems to be a general feeling that warfarin, with
      its requisite dose adjustments and INR monitoring, is an outdated drug and should
      be shelved in favour of this novel agent. The assumption is that the newer drug
      must be better and safer as well as easier to use. Much of the literature
      associated with dabigatran encourages this view, stressing that dabigatran is a
      'game changer' with the advantage of fixed dosing for most patients and no
      anticoagulation monitoring. In this paper we question whether dabigatran can
      really live up to these expectations. We suggest that the safe and effective
      prescribing of dabigatran, like all anticoagulants used in therapeutic doses,
      will most likely require dose individualisation and selective monitoring. This
      requirement should not be viewed as a failure for dabigatran but rather as a
      success for rational therapeutics.

PMID- 22854368
TI  - Spontaneous gastroduodenal artery aneurysm rupture in acute surgery.
AB  - Among the rarest of the visceral aneurysms, gastroduodenal artery (GDA) aneurysms
      often present with spontaneous rupture and are associated with a high mortality
      rate. Their aetiology is poorly understood. This report describes a case of
      haemorrhagic shock due to sudden GDA aneurysm rupture in a patient with a
      significant autoimmune history.

PMID- 22854369
TI  - Medical image. Microfilaria in a facial mass--a coincidental finding in fine
      needle aspiration cytology.

PMID- 22854370
TI  - Assessment of health and potential for milk based intervention to improve the
      nutrient intake of toddlers in New Zealand.

PMID- 22854371
TI  - New Zealand's smokefree prison policy appears to be working well: one year on.

PMID- 22854372
TI  - Majority support among the public, youth and smokers for retail-level controls to
      help end tobacco use in New Zealand.

PMID- 22854373
TI  - Use of a reminder sticker improves rates of documentation of resuscitation status
      and the appropriate prescription of venous thromboembolism prophylaxis.

PMID- 22854374
TI  - Improving hand hygiene in New Zealand hospitals to increase patient safety and
      reduce costs: results from the first hand hygiene national compliance audit for
      2012.

PMID- 22854375
TI  - APIC's 2012 Heroes of Infection Prevention.

PMID- 22854377
TI  - Pattern of bacterial colonization in a new neonatal intensive care unit and its
      association with infections in infants.
AB  - BACKGROUND: There is paucity of information on the pattern of bacterial
      colonization of a new neonatal intensive care unit. OBJECTIVE: To study the
      pattern of bacterial colonization on the environmental surfaces in a new neonatal
      intensive care unit (NICU) and correlate it with infections in the infants.
      METHODS: Environmental cultures from the faucets and computer keyboards in the
      NICU were obtained prospectively every 2 weeks for 1 year. Positive blood,
      cerebrospinal fluid, and respiratory cultures from the infants in the NICU were
      also obtained. RESULTS: A total of 175 swab cultures was collected, which were
      sterile for initial 6-week period. Subsequently, 31 cultures grew microbes: 26
      (83.8%) from the faucets and 5 (16.2%) from the computers keyboard (P < .001). Of
      the 48 positive blood cultures in NICU patients, 6 (12.5%) matched the organism
      growing from the surveillance sites, but the correlation was not significant (P =
      .076). None of the 31 positive respiratory cultures and 1 positive cerebrospinal
      fluid culture correlated to the organisms grown from the NICU environment.
      CONCLUSION: The environment was colonized after an initial period of sterile
      cultures in a new NICU. Once colonized, they can persist, increasing the risk of
      developing resistance to antibiotics. They did not correlate with the positive
      cultures from the infants admitted to the NICU during the study period.

PMID- 22854376
TI  - Nurse staffing, burnout, and health care-associated infection.
AB  - BACKGROUND: Each year, nearly 7 million hospitalized patients acquire infections
      while being treated for other conditions. Nurse staffing has been implicated in
      the spread of infection within hospitals, yet little evidence is available to
      explain this association. METHODS: We linked nurse survey data to the
      Pennsylvania Health Care Cost Containment Council report on hospital infections
      and the American Hospital Association Annual Survey. We examined urinary tract
      and surgical site infection, the most prevalent infections reported and those
      likely to be acquired on any unit within a hospital. Linear regression was used
      to estimate the effect of nurse and hospital characteristics on health care
      associated infections. RESULTS: There was a significant association between
      patient-to-nurse ratio and urinary tract infection (0.86; P = .02) and surgical
      site infection (0.93; P = .04). In a multivariate model controlling for patient
      severity and nurse and hospital characteristics, only nurse burnout remained
      significantly associated with urinary tract infection (0.82; P = .03) and
      surgical site infection (1.56; P < .01) infection. Hospitals in which burnout was
      reduced by 30% had a total of 6,239 fewer infections, for an annual cost saving
      of up to $68 million. CONCLUSIONS: We provide a plausible explanation for the
      association between nurse staffing and health care-associated infections.
      Reducing burnout in registered nurses is a promising strategy to help control
      infections in acute care facilities.

PMID- 22854378
TI  - An outbreak of Klebsiella pneumoniae late-onset sepsis in a neonatal intensive
      care unit in Guatemala.
AB  - BACKGROUND: Gram-negative bloodstream infections are an important cause of
      neonatal mortality. In October 2009, we investigated a Klebsiella spp outbreak in
      a neonatal intensive care unit in Guatemala. METHODS: Probable cases were defined
      as a Klebsiella spp isolated from blood in neonates aged <28 days in the neonatal
      intensive care unit between October 1 and November 10, 2009; confirmed cases were
      identified as Klebsiella pneumoniae. Clinical data were abstracted from medical
      charts. K pneumoniae isolates were genotyped by pulsed-field gel electrophoresis
      (PFGE) and tested for antimicrobial susceptibility. Infection control practices
      were inspected. RESULTS: There were 14 confirmed cases. The median age at onset
      of infection was 3 days (range, 2-8 days). Nine patients died (64%). K pneumoniae
      isolates were resistant to multiple antimicrobials. PFGE revealed 2 distinct
      clusters. Breaches in infection control procedures included inappropriate
      intravenous solution use and inadequate hand hygiene and contact precautions.
      CONCLUSIONS: We report a K pneumoniae outbreak with high neonatal mortality in
      Guatemala. PFGE clustering suggested a common source possibly related to reuse of
      a single-use intravenous medication or solution. The risk for K pneumoniae
      bloodstream infections in neonates in low-resource settings where sharing of
      solutions is common needs to be emphasized.

PMID- 22854379
TI  - Health care-associated infections studies project: an American Journal of
      Infection Control and National Healthcare Safety Network data quality
      collaboration case study 7.

PMID- 22854380
TI  - Comparison of antimicrobial resistance in neonatal and adult intensive care units
      in a tertiary teaching hospital.
AB  - Intrahospital variations in antimicrobial profiles may be related to many
      factors. This study compared causative agents of nosocomial bloodstream
      infections between a neonatal intensive care unit (NICU) that adopted a ward
      tailored antibiotic policy and adult intensive care units (ICUs). Data on
      organisms from blood cultures obtained from the respective wards between 2005 and
      2009 were analyzed. Compared with the adult ICUs, the NICU had a higher frequency
      of Enterobacteriacae and lower frequencies of typical hospital-acquired pathogens
      (eg, Klebsiella pneumoniae, 17.4% vs 10.0% [P < .001]; Acinetobacter baumannii,
      3.9% vs 11.6% [P < .001]). Antibiotic resistance of gram-negative organisms was
      also significantly lower in the NICU, including resistance to imipenem (5.7% vs
      32.1%; P < .001), amikacin (8.8% vs 30.3%), and ceftriaxone (36.1% vs 74.6%; P <
      .001). This could possibly be due to the ward-tailored antibiotic policy adopted
      by the NICU but not by the other ICUs.

PMID- 22854381
TI  - Pediatric physicians' knowledge, attitudes, and beliefs regarding Clostridium
      difficile-associated disease prevention, testing, and treatment.

PMID- 22854382
TI  - Comparative contamination rate of toys in kindergartens and households.

PMID- 22854383
TI  - The importance of infection prevention bundles related to
      construction/renovations in hospital environment.

PMID- 22854384
TI  - "Persistent activity"-should the effect of chlorhexidine in the sampling fluid
      and nutrient broth and on agar plates really be regarded as the effect on hands?

PMID- 22854385
TI  - Response to letter regarding "Prospective, randomized in vivo comparison of a
      dual-active antiseptic versus two alcohol-only waterless antiseptics for surgical
      hand antisepsis".

PMID- 22854386
TI  - Silent gout: an unusual presentation in diabetic neuropathy.
AB  - INTRODUCTION: Foot pathology presents a diagnostic challenge in diabetic patients
      with co-existent peripheral neuropathy. Pain is a key feature that assists in
      accurate diagnosis of disease and monitoring response to treatment. CASE REPORT:
      We present a 71-year-old gentleman with peripheral neuropathy who reported mild
      midfoot pain that was associated with bony erosions throughout the midfoot. He
      had recently undergone amputation of the 5th toe that proved to be associated
      with staphylococcal infection and a presumptive diagnosis of osteomyelitis was
      made. Subsequent deep tissue sampling confirmed a diagnosis of severe tophaceous
      gout that had been masked by his peripheral neuropathy. DISCUSSION: This case
      represents an unusual presentation of gout affecting the midfoot in a diabetic
      with peripheral neuropathy. It serves as a reminder of the importance of tissue
      sampling in these cases to confirm diagnosis before a definitive treatment plan
      is made.

PMID- 22854387
TI  - Lower pole vessels in children with pelviureteric junction obstruction:
      laparoscopic vascular hitch or dismembered pyeloplasty?
AB  - OBJECTIVE: To choose between laparoscopic "vascular hitch" (VH) and dismembered
      pyeloplasty (DP) in treatment of aberrant lower pole crossing vessels potentially
      responsible for pelviureteric junction obstruction (PUJO) in older children.
      PATIENTS AND METHODS: Retrospective study of 19 patients treated laparoscopically
      for PUJO. Based on videos of the procedures, we studied the anatomical
      relationship between the renal pelvis, the pelviureteric junction, and the
      aberrant vessels. RESULTS: Eight patients had laparoscopic VH and 11 had DP. All
      patients with DP needed drainage. In the VH group, 7/8 patients were asymptomatic
      and had decreased pelvic dilation. Half of them accepted MAG3 scintigraphy, and
      in these patients the obstructive syndrome disappeared completely. The last
      patient in this group was lost to follow-up. We observed three anatomical
      variations in the location of polar vessels: type 1 (in front of the dilated
      pelvis), type 2 (in front of the pelviureteric junction), type 3 (under the
      pelviureteric junction, resulting in ureteral kinking). CONCLUSION: Laparoscopic
      VH is a simple technique involving no urinary anastomosis or drainage, but we
      cannot guarantee that the crossing vessels are the sole etiology for PUJO.
      Following our experience, only patients with type 3 anatomical variations and
      with a normal pelviureteric junction should be proposed for VH.

PMID- 22854388
TI  - Foreskin reconstruction does not increase urethroplasty or skin complications
      after distal TIP hypospadias repair.
AB  - AIM: To compare urethral and skin complications between consecutive patients
      undergoing distal TIP (tubularized incised plate) hypospadias repair with
      prepucioplasty versus circumcision. METHODS: Prospective case-cohort study
      comparing urethroplasty and skin complications between consecutive patients
      undergoing distal TIP with prepucioplasty versus circumcision. Those with <1
      month follow-up or prior circumcision were excluded. Decision for prepucioplasty
      or circumcision was made exclusively by caregivers. Operative technique was the
      same except skin closure. Postoperative foreskin retraction was deferred >=6
      weeks after prepucioplasty. RESULTS: Of 343 circumcision and 85 prepucioplasty
      cases, median age and follow-up were 8 (3-420) and 7 (1.5-97.5) months,
      respectively. Urethroplasty complications occurred in 30 (8.7%) circumcision
      patients [16 fistulas, 13 glans dehiscences, 1 meatal stenosis due to balanitis
      xerotic obliterans (BXO) 5 years postoperatively], versus 7 (8.0%) after
      prepucioplasty [4 fistulas, 2 glans dehiscences, 1 urethral stricture], p = 1.0.
      Skin complications resulting in reoperation occurred in 7 (2.0%) circumcision
      patients and 2 (2.3%) prepucioplasty patients, including an unsightly dorsal
      whorl in 1 and BXO 66 months postoperatively in another, p = 1.0. CONCLUSION:
      Prepucioplasty does not increase urethroplasty or skin complications after distal
      TIP hypospadias repair. We found no contraindication for prepucioplasty among
      consecutive patients, indicating hypospadiologists can manage the foreskin in
      distal repairs according to caregiver preference.

PMID- 22854393
TI  - Staff perceptions on Newborn Individualized Developmental Care and Assessment
      Program (NIDCAP) during its implementation in two Spanish neonatal units.
AB  - BACKGROUND: The implementation of the Newborn Individualized Developmental Care
      and Assessment Program (NIDCAP) requires great effort. Few studies evaluating
      staff perception of NIDCAP exist, especially in Southern Europe, and these few
      studies usually have a low representation of the medical staff. AIMS: Exploration
      of staff perception (neonatologists, nurses and nursing assistants) of NIDCAP
      during its implementation and their attitude towards it and intention to put it
      into practice. STUDY DESIGN: This study is a descriptive survey measuring staff
      perceptions of NIDCAP and its effects on their work in two Spanish neonatal level
      III intensive care units (NICUs). Validated questionnaires were distributed to
      neonatologists, nurses and nursing assistants of which 305 were completed
      (response rate: 85%). RESULT: Virtually all the items which assess the infant's
      well being and the parents' role received a positive evaluation. However, three
      items got slightly negative evaluations: NIDCAP was more time consuming and
      nurses' working conditions and lighting in the unit were less optimal than in
      earlier practices. The professionals also had a positive attitude and a
      willingness to use the NIDCAP. Neonatologists perceived NIDCAP more positively
      than the nursing staff with statistically significant differences. CONCLUSION:
      The neonatal unit staff in two Spanish NICUs perceived NIDCAP positively. This
      assessment is more positive for neonatologists than for nurses.

PMID- 22854394
TI  - Perineural clonidine does not prolong levobupivacaine 0.5% after sciatic nerve
      block using the Labat approach in foot and ankle surgery.
AB  - BACKGROUND: There is controversy about the effectiveness of perineural clonidine
      used as an adjuvant to local anesthetics. This study investigated whether the
      addition of 150 MUg clonidine to 0.5% levobupivacaine used for posterior sciatic
      nerve block would prolong the duration of analgesia. METHODS: This double-blind,
      prospective trial compared the analgesic characteristics of 20 mL plain
      levobupivacaine versus 20 mL levobupivacaine 0.5% plus 150 MUg clonidine in a
      posterior sciatic nerve block (Labat approach) for foot and ankle surgery. Sixty
      patients were randomized and allocated to receive either levobupivacaine alone or
      levobupivacaine plus clonidine, to find a 30% prolongation of analgesia with the
      adjuvant, using the same SD. The onset and duration of the block (time from
      completion of block administration to first morphine request), the hemodynamic
      changes during surgery, the need for rescue analgesia, and technical or
      neurologic complications were assessed over a 24-hour period. RESULTS: The onset
      of sensory block (in minutes) was similar in the levobupivacaine and
      levobupivacaine plus clonidine groups (10 [5-20] vs 10 [5-23] minutes, median
      [interquartile range], respectively), as was the time to first request of pain
      medication (1215 [920-1530] vs 1275 [1067-1360] minutes, respectively). However,
      during surgery, statistically significantly more subjects in the levobupivacaine
      plus clonidine group than the levobupivacaine group experienced a decrease of
      more than 20% in systolic arterial pressure (50% vs 28% of patients,
      respectively; P < 0.028). No complications were noted in either group over 24
      hours. CONCLUSIONS: Addition of 150 MUg clonidine to 20 mL of levobupivacaine
      0.5% in posterior gluteal (Labat) sciatic nerve block did not prolong the
      duration of analgesia but had a slight effect on systolic arterial pressure.

PMID- 22854396
TI  - Regional anesthesia and analgesia in critically ill patients: a systematic
      review.
AB  - Regional anesthesia has become invaluable for the treatment of pain during and
      after a wide range of surgical procedures. However, its benefits in the
      nonsurgical setting have been less well studied. Regional anesthesia is an
      appealing modality for critically ill patients, providing focused and sustained
      pain control with beneficial systemic effect profiles. Indications for regional
      anesthesia in this patient group are not limited to surgical and postsurgical
      analgesia but expand to the management of trauma-related issues, medical
      conditions, and painful procedures at the bedside. Patients in the critical care
      unit present special challenges to the regional anesthesiologist, including
      coagulopathies, infections, immunocompromised states, sedation- and ventilation
      associated problems, and factors potentially increasing the risk for systemic
      toxicity. This review is intended to evaluate the role of regional anesthesia in
      critically ill patients, to discuss potential benefits, and to provide a summary
      of the published evidence on the subject.

PMID- 22854395
TI  - Ultrasound-guided ankle block for forefoot surgery: the contribution of the
      saphenous nerve.
AB  - BACKGROUND: Ankle blocks typically include the block of 5 nerves, the 4 branches
      that trace their origin back to the sciatic nerve plus the saphenous nerve (SaN).
      The sensory area of the SaN in the foot is variable. Based on our clinical
      experience, we decided to study the sensory distribution of the SaN in the foot
      and determine whether the block of this nerve is necessary as a component of an
      ultrasound-guided ankle block for bunion surgery. METHODS: One hundred patients
      scheduled for bunion surgery under ankle block were prospectively studied. We
      performed ultrasound-guided individual blocks of the tibial, deep peroneal,
      superficial peroneal, and sural nerves. After obtaining complete sensory block of
      these nerves, we mapped the SaN sensory territory as such area without anesthesia
      on the medial side of the foot. RESULTS: Every nerve block was successful within
      10 minutes of injection. The saphenous territory extended into the foot to 57 +/-
      13 mm distal to the medial malleolus. This distal margin was 22 +/- 11 mm
      proximal to the first tarsometatarsal joint. The proximal end of the surgical
      incision was located 1 cm distal to the first tarsometatarsal joint. In only 3
      patients (3%), the area of SaN innervation reached the proximal end of the
      planned incision. CONCLUSIONS: Ultrasound-guided ankle block is a highly
      effective technique for bunion surgery. The sensory territory of the SaN in the
      foot seems to extend only to the midfoot. According to our sample, 97% of the
      patients undergoing bunion surgery under an ankle block would not benefit from
      having a SaN block.

PMID- 22854397
TI  - Reliability of static and dynamic quantitative sensory testing in patients with
      painful chronic pancreatitis.
AB  - BACKGROUND AND OBJECTIVES: Quantitative sensory testing (QST) has proven to be an
      important instrument to characterize mechanisms underlying somatic and
      neuropathic pain disorders. However, its reliability has not previously been
      established in patients with visceral pain. We investigated the test-retest
      reliability of static and dynamic QST in patients with visceral pain due to
      chronic pancreatitis. METHODS: Sixty-two patients (38 men, 53 [11] y) with
      painful chronic pancreatitis were included. Static QST comprised sensory
      thresholds for pressure and electrical stimulation performed in the ventral and
      dorsal T10 dermatomes (sharing spinal innervation with the pancreas, ie,
      pancreatic viscerotomes) and in 4 heterologous regions (control areas). Dynamic
      QST comprised conditioned pain modulation. Measurements were obtained from 2
      subsequent test sessions separated by 1 week. RESULTS: The reliability of static
      QST was generally high, with the best test-retest performance seen for pressure
      pain thresholds (intraclass correlation coefficients [ICC], 0.74) and electrical
      sensation thresholds (ICC, 0.66). In contrast, the reliability of dynamic QST was
      poor (ICC, 0.01). For static QST measures, the reliability was higher for pain
      thresholds compared with suprapain thresholds (P < 0.01). No differences between
      assessments in the pancreatic viscerotomes compared with heterologous regions
      were seen (P = 0.6). CONCLUSIONS: Sensory thresholds in the pancreatic
      viscerotomes and control areas were reproducible over time. In contrast, dynamic
      QST measurements reflecting active central modulation of pain processing state
      (ie, conditioned pain modulation) were not stable over time and showed
      considerable variability. These factors should be taken into consideration in
      case QST is used to follow disease mechanisms, drug effects, or effects of pain
      intervention.

PMID- 22854399
TI  - Sustainable diets for the future: Can we contribute to reducing greenhouse gas
      emissions by eating a healthy diet?
AB  - BACKGROUND: Food systems account for 18-20% of UK annual greenhouse gas emissions
      (GHGEs). Recommendations for improving food choices to reduce GHGEs must be
      balanced against dietary requirements for health. OBJECTIVE: We assessed whether
      a reduction in GHGEs can be achieved while meeting dietary requirements for
      health. DESIGN: A database was created that linked nutrient composition and GHGE
      data for 82 food groups. Linear programming was used iteratively to produce a
      diet that met the dietary requirements of an adult woman (19-50 y old) while
      minimizing GHGEs. Acceptability constraints were added to the model to include
      foods commonly consumed in the United Kingdom in sensible quantities. A sample
      menu was created to ensure that the quantities and types of food generated from
      the model could be combined into a realistic 7-d diet. Reductions in GHGEs of the
      diets were set against 1990 emission values. RESULTS: The first model, without
      any acceptability constraints, produced a 90% reduction in GHGEs but included
      only 7 food items, all in unrealistic quantities. The addition of acceptability
      constraints gave a more realistic diet with 52 foods but reduced GHGEs by a
      lesser amount of 36%. This diet included meat products but in smaller amounts
      than in the current diet. The retail cost of the diet was comparable to the
      average UK expenditure on food. CONCLUSION: A sustainable diet that meets dietary
      requirements for health with lower GHGEs can be achieved without eliminating meat
      or dairy products or increasing the cost to the consumer.

PMID- 22854398
TI  - Dietary fat quality and risk of sudden cardiac death in women.
AB  - BACKGROUND: Dietary n-3 PUFAs are inversely associated with risk of sudden
      cardiac death (SCD); however, little is known about other fats and SCD.
      Furthermore, concerns have been raised that high n-6 PUFA intake may attenuate
      the benefits of n-3 PUFAs. OBJECTIVE: We examined associations and selected
      interactions between dietary fatty acids, expressed as a proportion of total fat
      and SCD. DESIGN: We conducted a prospective cohort study among 91,981 women aged
      34-59 y from the Nurses' Health Study in 1980. Over 30 y, we documented 385 SCDs.
      RESULTS: In multivariable models, women in the highest compared with the lowest
      quintile of SFA intake had an RR of SCD of 1.44 (95% CI: 1.04, 1.98). Conversely,
      women in the highest compared with the lowest quintile of PUFA intake had an RR
      of SCD of 0.57 (95% CI: 0.41, 0.78). Intakes of n-6 and n-3 PUFAs were both
      significantly associated with a lower risk of SCD, and n-6 PUFAs did not modify
      the association between n-3 PUFAs and SCD. MUFAs and trans fats were not
      associated with SCD risk. After further adjustment for coronary heart disease
      (CHD) and CHD risk factors potentially in the causal pathway, the association
      between PUFAs and SCD remained significant, whereas the association for SFAs was
      no longer significant. CONCLUSIONS: Intake of PUFAs as a proportion of fat was
      inversely associated with SCD risk, independent of traditional CHD risk factors.
      These results support dietary guidelines to improve dietary fat quality by
      replacing intake of SFAs with n-6 and n-3 PUFAs.

PMID- 22854400
TI  - Caloric compensation and eating in the absence of hunger in 5- to 12-y-old weight
      discordant siblings.
AB  - BACKGROUND: An impaired ability to compensate for calories and increased eating
      in the absence of hunger (EAH) has been associated with increased energy intake
      and weight gain in unrelated children. OBJECTIVE: The aims of this study were to
      compare caloric compensation [the percentage compensation index (%COMPX)] and EAH
      in weight-discordant siblings aged 5-12 y. DESIGN: In a crossover, behavioral
      genetics design, 47 same-sex sibling pairs (53% female, 55% full siblings) were
      served dinner once a week for 3 wk. Across conditions, siblings were served the
      same dinner, but 25 min before dinner, they either consumed in full or did not
      consume 1 of 2 preloads that varied in energy density (ED; 0.57 or 0.97 kcal/g).
      On the day when no preload was consumed, EAH was assessed after dinner and
      defined as the number of calories consumed from snacks. RESULTS: Overweight/obese
      siblings undercompensated [%COMPX: -48.8 +/- 56.3 (mean +/- SEM)] and therefore
      overate after the high-ED preload, whereas normal-weight siblings showed accurate
      compensation (%COMPX: 101.3 +/- 51.9; P = 0.03). Furthermore, overweight/obese
      siblings consumed 34% more calories (93 kcal) in the absence of hunger than did
      normal-weight siblings (P = 0.01). Within-pair resemblances for %COMPX and EAH
      were stronger for full siblings (P < 0.049) than for half siblings (P > 0.23).
      CONCLUSIONS: An impaired ability to regulate short-term energy intake, which
      includes incomplete adjustment for calorie differences in a preload and eating
      when satiated, may represent a behavioral phenotype for obesity in children.
      Future studies should test whether teaching children to focus on internal satiety
      cues may prevent at-risk children from overeating.

PMID- 22854401
TI  - Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed
      with blackcurrants and lingonberries in healthy women.
AB  - BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In
      vitro studies suggest that berries may reduce the digestion and absorption of
      sucrose and thereby suppress postprandial glycemia, but the evidence in humans is
      limited. OBJECTIVE: We investigated the effects of sucrose ingested with
      blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on
      postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty
      healthy women participated in a randomized, controlled, crossover meal study.
      They consumed whole blackcurrants or lingonberries (150 g served as purees) or
      blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose.
      Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were
      collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with
      sucrose alone, ingestion of sucrose with whole berries resulted in reduced
      glucose and insulin concentrations during the first 30 min and a slower decline
      during the second hour and a significantly improved glycemic profile. Berries
      prevented the sucrose-induced late postprandial hypoglycemic response and the
      compensatory free fatty acid rebound. Nearly similar effects were observed when
      sucrose was consumed with berry nectars. The improved responses were evident
      despite the higher content of available carbohydrate in the berry and nectar
      meals, because of the natural sugars present in berries. CONCLUSIONS:
      Blackcurrants and lingonberries, as either whole berries or nectars, optimize the
      postprandial metabolic responses to sucrose. The responses are consistent with
      delayed digestion of sucrose and consequent slower absorption of glucose.

PMID- 22854402
TI  - High-dose cholecalciferol reduces parathyroid hormone in patients with early
      chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Vitamin D deficiency contributes to secondary hyperparathyroidism,
      which occurs early in chronic kidney disease (CKD). OBJECTIVES: We aimed to
      determine whether high-dose cholecalciferol supplementation for 1 y in early CKD
      is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D
      [25(OH)D] concentration >=30 ng/mL) and decrease serum parathyroid hormone (PTH).
      A secondary aim was to determine the effect of cholecalciferol on blood pressure
      and serum fibroblast growth factor-23 (FGF23). DESIGN: This was a double-blind,
      randomized, placebo-controlled trial. Forty-six subjects with early CKD (stages 2
      3) were supplemented with oral cholecalciferol (vitamin D group; 50,000 IU/wk for
      12 wk followed by 50,000 IU every other week for 40 wk) or a matching placebo for
      1 y. RESULTS: By 12 wk, serum 25(OH)D increased in the vitamin D group only
      [baseline (mean +/- SD): 26.7 +/- 6.8 to 42.8 +/- 16.9 ng/mL; P < 0.05] and
      remained elevated at 1 y (group-by-time interaction: P < 0.001). PTH decreased
      from baseline only in the vitamin D group (baseline: 89.1 +/- 49.3 to 70.1 +/-
      24.8 pg/mL; P = 0.01) at 12 wk, but values were not significantly different from
      baseline at 1 y (75.4 +/- 29.5 pg/mL; P = 0.16; group-by-time interaction: P =
      0.09). Group differences were more pronounced in participants with secondary
      hyperparathyroidism (group-by-time interaction: P = 0.004). Blood pressure and
      FGF23 did not change in either group. CONCLUSIONS: After 1 y, this oral
      cholecalciferol regimen was safe and sufficient to maintain serum 25(OH)D
      concentrations and prevent vitamin D insufficiency in early CKD. Furthermore,
      serum PTH improved after cholecalciferol treatment, particularly in patients who
      had secondary hyperparathyroidism.

PMID- 22854403
TI  - Intraduodenal protein modulates antropyloroduodenal motility, hormone release,
      glycemia, appetite, and energy intake in lean men.
AB  - BACKGROUND: Intraduodenal fat and carbohydrate modulate antropyloroduodenal
      motility and hormone release and suppress appetite and energy intake in a load
      dependent manner. Protein also suppresses energy intake, but its effects on these
      gastrointestinal factors and their role in the appetite-suppressive effects of
      protein remain unclear. OBJECTIVE: We aimed to characterize the effects of
      different intraduodenal protein loads on antropyloroduodenal pressures,
      gastrointestinal hormone release, glucose and insulin concentrations, appetite
      perceptions, and energy intake. DESIGN: Sixteen lean, healthy men were studied on
      4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures,
      plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin,
      blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min
      intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline
      (control). Energy intakes at a buffet lunch consumed immediately after the
      infusion were quantified. RESULTS: Increases in the load of protein resulted in
      greater suppression of antral motility, greater stimulation of basal and isolated
      pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and
      greater suppression of energy intake. However, energy intake was reduced only
      after a protein load of 3 kcal/min compared with after all other treatments (P <
      0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP
      1, and insulin was related inversely with basal pyloric pressure (r = -0.51, P <
      0.001). CONCLUSION: The acute effects of intraduodenal protein on
      antropyloroduodenal motility, gastrointestinal hormone release, glucose, and
      insulin are load dependent and contribute to the suppression of energy intake.
      This trial was registered at www.anzctr.org.au as 12610000376044.

PMID- 22854404
TI  - Association between intake of artificially sweetened and sugar-sweetened
      beverages and preterm delivery: a large prospective cohort study.
AB  - BACKGROUND: Artificially sweetened (AS) and sugar-sweetened (SS) beverages are
      commonly consumed during pregnancy. A recent Danish study reported that the daily
      intake of an AS beverage was associated with an increased risk of preterm
      delivery. OBJECTIVE: We examined the intake of AS and SS beverages in pregnant
      women to replicate the Danish study and observe whether AS intake is indeed
      associated with preterm delivery. DESIGN: This was a prospective study of 60,761
      pregnant women in the Norwegian Mother and Child Cohort Study. Intakes of
      carbonated and noncarbonated AS and SS beverages and use of artificial sweeteners
      in hot drinks were assessed by a self-reported food-frequency questionnaire in
      midpregnancy. Preterm delivery was the primary outcome, and data were obtained
      from the Norwegian Medical Birth Registry. RESULTS: Intakes of both AS and SS
      beverages increased with increasing BMI and energy intake and were higher in
      women with less education, in daily smokers, and in single women. A high intake
      of AS beverages was associated with preterm delivery; the adjusted OR for those
      drinking >1 serving/d was 1.11 (95% CI: 1.00, 1.24). Drinking >1 serving of SS
      beverages per day was also associated with an increased risk of preterm delivery
      (adjusted OR: 1.25; 95% CI: 1.08, 1.45). The trend tests were positive for both
      beverage types. CONCLUSION: This study suggests that a high intake of both AS and
      SS beverages is associated with an increased risk of preterm delivery.

PMID- 22854405
TI  - Unmetabolized folic acid prevalence is widespread in the older Irish population
      despite the lack of a mandatory fortification program.
AB  - BACKGROUND: In 2006 the Food Safety Authority of Ireland recommended mandatory
      folic acid fortification of flour for the prevention of neural tube defects in
      addition to the existing extensive voluntary folic acid fortification culture in
      place there. This recommendation is now suspended until further scientific
      evidence surrounding safety becomes available. The safety issues include concerns
      about the masking of vitamin B-12 deficiency and potential cancer acceleration,
      both of which may be of concern for the elderly population. OBJECTIVE: The aim of
      this study was to measure the basal (fasted) concentrations of unmetabolized
      folic acid in the plasma of an elderly population group exposed to this liberal
      voluntary fortification of foodstuffs in Ireland. DESIGN: We invited participants
      aged 60-86 y from the Lifeways Cross-Generation Cohort Study to participate in
      this project. After providing informed consent, the participants were invited to
      provide fasting blood samples and to complete a standard food-frequency
      questionnaire and a questionnaire on recent and habitual intakes of folic acid.
      Samples were assayed for total plasma folate, red blood cell folate,
      homocysteine, and unmetabolized folic acid. RESULTS: A total of 137 subjects with
      a mean age of 67.4 y were studied. Unmetabolized folic acid was detected in 94.1%
      of the cohort with a mean concentration of 0.39 nmol/L (range: 0.07-1.59 nmol/L),
      accounting for 1.3% of total plasma folate. CONCLUSION: These results indicate
      unmetabolized folic acid in plasma in most of this elderly Irish cohort, even
      after an overnight fast. These results should be considered carefully by those
      legislating in this area.

PMID- 22854406
TI  - beta-Carotene in Golden Rice is as good as beta-carotene in oil at providing
      vitamin A to children.
AB  - BACKGROUND: Golden Rice (GR) has been genetically engineered to be rich in beta
      carotene for use as a source of vitamin A. OBJECTIVE: The objective was to
      compare the vitamin A value of beta-carotene in GR and in spinach with that of
      pure beta-carotene in oil when consumed by children. DESIGN: Children (n = 68;
      age 6-8 y) were randomly assigned to consume GR or spinach (both grown in a
      nutrient solution containing 23 atom% 2H2O) or [2H8]beta-carotene in an oil
      capsule. The GR and spinach beta-carotene were enriched with deuterium (2H) with
      the highest abundance molecular mass (M) at M(beta-C)+2H10. [13C10]Retinyl
      acetate in an oil capsule was administered as a reference dose. Serum samples
      collected from subjects were analyzed by using gas chromatography electron
      capture negative chemical ionization mass spectrometry for the enrichments of
      labeled retinol: M(retinol)+4 (from [2H8]beta-carotene in oil), M(retinol)+5
      (from GR or spinach [2H10]beta-carotene), and M(retinol)+10 (from [13C10]retinyl
      acetate). RESULTS: Using the response to the dose of [13C10]retinyl acetate (0.5
      mg) as a reference, our results (with the use of AUC of molar enrichment at days
      1, 3, 7, 14, and 21 after the labeled doses) showed that the conversions of pure
      beta-carotene (0.5 mg), GR beta-carotene (0.6 mg), and spinach beta-carotene (1.4
      mg) to retinol were 2.0, 2.3, and 7.5 to 1 by weight, respectively. CONCLUSIONS:
      The beta-carotene in GR is as effective as pure beta-carotene in oil and better
      than that in spinach at providing vitamin A to children. A bowl of ~100 to 150 g
      cooked GR (50 g dry weight) can provide ~60% of the Chinese Recommended Nutrient
      Intake of vitamin A for 6-8-y-old children.

PMID- 22854407
TI  - Food and nutrient intakes and their associations with lower BMI in middle-aged US
      adults: the International Study of Macro-/Micronutrients and Blood Pressure
      (INTERMAP).
AB  - BACKGROUND: Clinical trial data show that reduction in total energy intake
      enhances weight loss regardless of the macronutrient composition of the diet. Few
      studies have documented dietary patterns or nutrient intakes that favor leanness
      [BMI (in kg/m2) <=25] in free-living populations. OBJECTIVE: This investigation
      examined associations of usual energy, food, and nutrient intakes with BMI among
      US participants of the International Study of Macro-/Micronutrients and Blood
      Pressure (INTERMAP). DESIGN: The INTERMAP is an international cross-sectional
      study of dietary factors and blood pressure in men and women (ages 40-59 y) that
      includes 8 US population samples. The present study included data from 1794
      Americans who were not consuming a special diet and who provided four 24-h
      dietary recalls and 2 timed 24-h urine collections. Multivariable linear
      regression with the residual method was used to adjust for energy intake; sex
      specific associations were assessed for dietary intakes and urinary excretions
      with BMI adjusted for potential confounders including physical activity. RESULTS:
      Lower energy intake was associated with lower BMI in both sexes. Univariately,
      higher intakes of fresh fruit, pasta, and rice and lower intakes of meat were
      associated with lower BMI; these associations were attenuated in multivariable
      analyses. Lower urinary sodium and intakes of total and animal protein, dietary
      cholesterol, saturated fats, and heme iron and higher urinary potassium and
      intakes of carbohydrates, dietary fiber, and magnesium were associated with lower
      BMI in both sexes. CONCLUSION: The consumption of foods higher in nutrient-dense
      carbohydrate and lower in animal protein and saturated fat is associated with
      lower total energy intakes, more favorable micronutrient intakes, and lower BMI.

PMID- 22854408
TI  - Magnesium intake and colorectal tumor risk: a case-control study and meta
      analysis.
AB  - BACKGROUND: Dietary magnesium might be related to colorectal tumor risk through
      the pivotal roles of magnesium in cellular metabolism, insulin resistance, and
      systemic inflammation. OBJECTIVE: We evaluated the hypothesis of whether higher
      dietary magnesium intake is associated with reduced colorectal tumor risk.
      DESIGN: A case-control study on colorectal adenomas (768 cases; 709 polyp-free
      control subjects) and a meta-analysis of colorectal adenomas (3 case-control
      studies) and carcinomas (6 prospective cohort studies) were conducted. Dietary
      magnesium was estimated from food-frequency questionnaires in the case-control
      study and most studies in the meta-analyses. Data analysis comprised multiple
      logistic regression analysis (case-control study) and fixed- and random-effects
      meta-analyses. RESULTS: The case-control study showed a nonsignificant inverse
      association between dietary magnesium intake and risk of colorectal adenomas (OR
      for every 100-mg/d increase: 0.81; 95% CI: 0.62, 1.06). However, inverse
      associations were observed only in subjects with BMI (in kg/m2) >=25, in subjects
      aged >=55 y, and for advanced adenomas. Associations did not vary by the calcium
      to-magnesium intake ratio. In the meta-analysis, every 100-mg/d increase in
      magnesium intake was associated with 13% lower risk of colorectal adenomas (OR:
      0.87; 95% CI: 0.75, 1.00) and 12% lower risk of colorectal cancer (RR: 0.88; 95%
      CI: 0.81, 0.97). CONCLUSIONS: Our findings support the hypothesis that higher
      intakes of dietary magnesium are associated with lower risk of colorectal tumors.
      The consumption of magnesium-rich foods may be a new avenue to explore further in
      the search for cancer-prevention strategies.

PMID- 22854409
TI  - Low-calorie sweetener consumption is increasing in the United States.
AB  - BACKGROUND: Low-calorie and no-calorie sweeteners (LCSs) have emerged as
      alternatives to added sugars. Research suggests that consumption among all
      Americans is increasing, yet it is unknown whether consumption trends differ
      among population subgroups. OBJECTIVE: Our study aimed to assess recent national
      trends in LCS consumption among children and other demographic subgroups in the
      United States. DESIGN: We used NHANES data collected in five 2-y cycles from 1999
      2000 to 2007-2008. Consumption of foods and beverages with LCSs was estimated by
      using one 24-h dietary recall. Estimates of the proportion of the population
      consuming foods and beverages containing LCSs (prevalence of consumption) were
      weighted to obtain nationally representative results. Trends in prevalence of LCS
      consumption and mean intake of beverages sweetened with LCSs were tested by using
      chi-square tests for trend and F tests. RESULTS: In 2007-2008, the percentage of
      children and adults consuming foods and beverages containing LCSs increased. The
      prevalence of consuming beverages with LCSs increased from 6.1% to 12.5% among
      children (P-trend < 0.0001) and from 18.7% to 24.1% among adults (P < 0.001).
      Increases in the prevalence of consumption of calorie-containing beverages with
      LCSs were observed among all weight, age, socioeconomic, and race-ethnicity
      subgroups in both children and adults. However, little change in consumption of
      no-calorie beverages with LCSs or LCS-containing foods was found. CONCLUSIONS:
      The consumption of LCS-containing beverages has doubled among US children over
      the past decade. Further research is needed to understand the health effects of
      this trend.

PMID- 22854410
TI  - Sodium and potassium intakes among US adults: NHANES 2003-2008.
AB  - BACKGROUND: The American Heart Association (AHA), Institute of Medicine (IOM),
      and US Departments of Health and Human Services and Agriculture (USDA) Dietary
      Guidelines for Americans all recommend that Americans limit sodium intake and
      choose foods that contain potassium to decrease the risk of hypertension and
      other adverse health outcomes. OBJECTIVE: We estimated the distributions of usual
      daily sodium and potassium intakes by sociodemographic and health characteristics
      relative to current recommendations. DESIGN: We used 24-h dietary recalls and
      other data from 12,581 adults aged >=20 y who participated in NHANES in 2003
      2008. Estimates of sodium and potassium intakes were adjusted for within
      individual day-to-day variation by using measurement error models. SEs and 95%
      CIs were assessed by using jackknife replicate weights. RESULTS: Overall, 99.4%
      (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended
      by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM
      Tolerable Upper Intake Level (2300 mg). In US adults who are recommended by the
      Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African
      Americans aged >=51 y or persons with hypertension, diabetes, or chronic kidney
      disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d, and 60.4% consumed
      >3000 mg/d-more than double the recommendation. Overall, <2% of US adults and ~5%
      of US men consumed >=4700 mg K/d (ie, met recommendations for potassium).
      CONCLUSION: Regardless of recommendations or sociodemographic or health
      characteristics, the vast majority of US adults consume too much sodium and too
      little potassium.

PMID- 22854411
TI  - Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and
      habitual caffeine consumption.
AB  - BACKGROUND: Recent genome-wide association studies (GWASs) from populations of
      European descent identified single nucleotide polymorphisms (SNPs) in aryl
      hydrocarbon receptor (AHR) and cytochrome P450 1A1 and 1A2 (CYP1A1-CYP1A2) genes
      that are associated with habitual caffeine and coffee consumption. OBJECTIVE: We
      examined whether these SNPs (AHR: rs6968865 and rs4410790; CYP1A1-CYP1A2:
      rs2472297 and rs2470893) and 6 additional tag SNPs in the AHR gene were
      associated with habitual caffeine consumption in a Costa Rican population.
      DESIGN: Subjects were from a case-control study of gene-diet interactions and
      myocardial infarction. Subjects with hypertension or missing information on
      smoking, caffeine intake, or genotype were excluded. Subjects were genotyped by
      using polymerase chain reaction with mass spectrometry-based detection, and
      caffeine intake was assessed by using a validated food-frequency questionnaire.
      RESULTS: Compared with subjects who consumed <100 mg caffeine/d, subjects who
      consumed >400 mg caffeine/d were more likely to be carriers of the T, C, or T
      allele for rs6968865, rs4410790, and rs2472297, respectively. The corresponding
      ORs and 95% CIs were 1.41 (1.03, 1.93), 1.41 (1.04, 1.92), and 1.55 (1.01, 2.36).
      Multivariate-adjusted ORs (95% CIs) for rs6968865 were 1.44 (1.03, 2.00) for all
      subjects, 1.75 (1.16, 2.65) for nonsmokers, 1.15 (0.58, 2.30) for current
      smokers, 2.42 (1.45, 4.04) for subjects >57 y old, and 1.00 (0.65, 1.56) for
      subjects <=57 y old. A similar effect modification was observed for rs4410790 but
      not for rs2472297. CONCLUSION: Our findings show that previous associations
      between SNPs in AHR and CYP1A1-CYP1A2 and caffeine and coffee consumption from
      GWASs in European populations are also observed in an ethnically distinct Costa
      Rican population, but age and smoking are important effect modifiers.

PMID- 22854412
TI  - Manipulating antioxidant intake in asthma: a randomized controlled trial.
AB  - BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence
      in epidemiologic studies. We previously showed that short-term manipulation of
      antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The
      objective was to investigate the effects of a high-antioxidant diet compared with
      those of a low-antioxidant diet, with or without lycopene supplementation, in
      asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high
      antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46)
      or a low-antioxidant diet (<=2 servings of vegetables and 1 serving of fruit
      daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled
      supplementation trial. Subjects who consumed the high-antioxidant diet received
      placebo. Subjects who consumed the low-antioxidant diet received placebo or
      tomato extract (45 mg lycopene/d). The intervention continued until week 14 or
      until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low
      antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s
      and percentage predicted forced vital capacity than did those consuming the high
      antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma
      C-reactive protein at week 14. At the end of the trial, time to exacerbation was
      greater in the high-antioxidant than in the low-antioxidant diet group, and the
      low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as
      likely to exacerbate. Of the subjects in the low-antioxidant diet group, no
      difference in airway or systemic inflammation or clinical outcomes was observed
      between the groups that consumed the tomato extract and those who consumed
      placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical
      asthma outcomes. Improvements were evident only after increased fruit and
      vegetable intake, which suggests that whole-food interventions are most
      effective. This trial was registered at http://www.actr.org.au as
      ACTRN012606000286549.

PMID- 22854413
TI  - Functionally selective AT(1) receptor activation reduces ischemia reperfusion
      injury.
AB  - Angiotensin II (AngII) is a key peptide in cardiovascular homeostasis and is a
      ligand for the Angiotensin II type 1 and 2 seven transmembrane receptors (AT(1)R
      and AT(2)R). The AT(1) receptor is a seven-transmembrane (7TM) G protein-coupled
      receptor (GPCR) mediating the majority of the physiological functions of AngII.
      The AT(1)R mediates its effects through both G protein-dependent and independent
      signaling, which can be separated by functionally selective agonists. In the
      present study we investigate the effect of AngII and the beta-arrestin biased
      agonist [SII]AngII on ischemia-reperfusion injury in rat hearts. Isolated hearts
      mounted in a Langendorff perfused rat heart preparations showed that
      preconditioning with [SII]AngII reduced the infarct size induced by global
      ischemia from 46+/-8.4% to 22+/-3.4%. In contrast, neither preconditioning with
      AngII nor postconditioning with AngII or [SII]AngII had a protective effect.
      Together these results demonstrate a cardioprotective effect of simultaneous
      blockade of G protein signaling and activation of G protein independent signaling
      through AT(1) receptors.

PMID- 22854414
TI  - Microelectrode recording duration and spatial density constraints for automatic
      targeting of the subthalamic nucleus.
AB  - BACKGROUND: Accurate detection of the boundaries of the subthalamic nucleus (STN)
      in deep brain stimulation (DBS) surgery using microelectrode recording (MER) is
      considered to refine localization and may therefore improve clinical outcome.
      However, MER tends to extend operation time and its cost-utility balance has been
      debated. OBJECTIVES: To quantify the tradeoff between accuracy of STN
      localization and the spatial and temporal parameters of MER that effect the
      operation time using an automated detection method. METHODS: We retrospectively
      estimated the accuracy of STN detection on data from 100 microelectrode
      trajectories. Our dense (average step = 0.12 mm) and long (average duration =
      22.5 s) MER data was downsampled in the spatial and temporal domains. Then, the
      STN borders were detected automatically on both the downsampled and original data
      and compared to each other. RESULTS: With a recording duration of 16 s, average
      accuracy for detecting STN entry ranged from 0.06 mm for a 0.1-mm step to 0.51 mm
      for a 1.0-mm step. Smaller effects were found along the temporal axis. For
      example, a 0.1-mm recording step yielded an STN entry average accuracy ranging
      from 0.06 mm for a 16-second recording duration to 0.16 mm for 0.1 s.
      CONCLUSIONS: STN entry detection error was about half of the step size. Sampling
      duration of STN activity can be minimized to 1 s/record without compromising
      accuracy. We conclude that bilateral DBS surgery time utilizing MER may be
      significantly shortened without compromising targeting accuracy.

PMID- 22854415
TI  - Fact or faith?: on the evidence for psychotherapy for adults with intellectual
      disability and mental health needs.
AB  - PURPOSE OF REVIEW: This article summarizes research and commentaries on
      psychotherapy for adults with intellectual disabilities published since 2008.
      RECENT FINDINGS: There have been very few empirical studies of the effectiveness
      of psychotherapy in this context over recent years despite a strong perception
      that such approaches are not only necessary but also of great value. There have
      been some interesting, though so far only suggestive, findings concerning the
      relationship between intellectual level and suitability for treatment, primarily
      with cognitive behavioural therapy. Therapies based on mindfulness are emerging
      as important new developments. Despite their heritage, psychodynamic approaches
      continue to rely on opinion over evidence to support their use. SUMMARY: Research
      on both processes in therapy and its outcomes needs to be undertaken with renewed
      vigour if specialist psychotherapy for people with intellectual disability is to
      flourish, or indeed survive, in the public healthcare system. However, it may
      have much a broader value for people with intellectual disability, especially
      those in residential services, than can be easily quantified.

PMID- 22854416
TI  - Prison psychiatry.
AB  - PURPOSE OF REVIEW: Prison psychiatry is a secluded area of the psychiatric care
      system, which in fact often provides treatment for those who do not have access
      to community-based healthcare systems. The aim of this review is to give an
      impression of the special challenges of psychiatric work behind bars and to
      emphasize current trends in prison psychiatry. RECENT FINDINGS: In prisoners,
      mental disorders are more common than in the general population. There is
      evidence that prison suicide rates do not reflect general population suicide
      rates, suggesting that variation in prison suicide rates possibly also reflects
      differences in the provision of psychiatric care. Good transitional preparation
      preceding release seems to be necessary to reduce the risk of poor health
      outcome, but is hard to achieve. Up to now, there is no clear decision on whether
      it is useful or possible to treat adult prisoners with attention
      deficit/hyperactivity disorder with stimulants. SUMMARY: Prison psychiatry has to
      deal with a disproportionate burden of psychiatric disease in prisoners. Adequate
      psychiatric treatment options may reduce suicide behind bars. Further research
      should focus on the special needs of individuals who are out of reach of the
      conventional community-based health system.

PMID- 22854417
TI  - Current world literature.

PMID- 22854419
TI  - Adipokines, insulin resistance and hyperandrogenemia in obese patients with
      polycystic ovary syndrome: cross-sectional correlations and the effects of weight
      loss.
AB  - OBJECTIVE: To assess the effects of weight loss on serum adipokine levels in
      polycystic ovary syndrome (PCOS). METHODS: We determined serum leptin,
      adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS
      and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks
      of treatment with orlistat 120 mg 3 times per day along with an energy-restricted
      diet. RESULTS: At baseline, serum visfatin concentration was higher in patients
      with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and
      resistin did not differ between the two groups. After 24 weeks, a significant
      reduction in BMI and waist circumference was observed in both patients with PCOS
      and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels
      decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both
      groups). The reduction in serum leptin levels did not differ between groups.
      Serum adiponectin, resistin, and visfatin levels did not change in either group.
      CONCLUSIONS: Leptin, adiponectin, and resistin do not appear to play major
      pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin
      emerges as a potentially important mediator of the endocrine abnormalities of
      these patients. However, serum visfatin levels are not substantially affected by
      weight loss.

PMID- 22854420
TI  - Neuropsychiatric symptoms in mild dementia with lewy bodies and Alzheimer's
      disease.
AB  - BACKGROUND/AIMS: To compare neuropsychiatric symptoms in patients with
      Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). METHODS:
      Neuropsychiatric symptoms and caregiver distress were assessed using the
      Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and
      compared across the two groups using non-parametric tests. RESULTS: The DLB
      patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more
      numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant
      symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2,
      p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on
      the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). CONCLUSIONS: In
      mild dementia, DLB patients have more neuropsychiatric symptoms and more
      associated caregiver distress compared with AD.

PMID- 22854421
TI  - Measures of impact: diabetes and urothelial cancer.

PMID- 22854422
TI  - Factors affecting 5- and 10-year survival of women with breast cancer: an
      analysis based on a public general hospital in Barcelona.
AB  - BACKGROUND: Data from a long-established hospital-based cancer registry were used
      to analyse the relationship between clinical and organisational factors and
      disease-specific survival among women with primary breast cancer. METHODS: 2023
      women with incident invasive breast cancer diagnosed from 1992 to 2005 were
      identified through the Hospital del Mar Cancer Registry (Barcelona, Spain).
      Patients were followed until December 2008. One-, 5- and 10-year disease-specific
      survival rates were estimated. Kaplan-Meier and Cox regression models were used
      to analyse death from breast cancer. RESULTS: At diagnosis 70.2% of tumours were
      in stages I-II. During follow-up 705 deaths occurred, 58.4% specifically due to
      breast cancer. Five- and 10-year breast cancer specific survival rates were 83.3%
      and 73.7%, respectively (stage I, 97.1% and 94.0%; stage II, 88.0% and 79.4%;
      stage III, 70.1% and 46.3%, and stage IV, 24.5% and 6.1%, respectively). The 5
      year disease-specific survival rate increased from 73.5% in 1992-1995 to 86.4% in
      2001-2005 (log rank, p<0.001). Multivariate analyses showed that prognosis was
      less favourable for women diagnosed between 1992 and 1995, for those whose route
      to diagnosis was not the screening programme, women aged >= 70 years, with stage
      IV tumours, with high grade lesions, and for women who received only palliative
      or symptomatic treatment. Adjusting for prognostic factors, surgeon's experience
      did not significantly appeared to affect survival of operated women. CONCLUSIONS:
      In this centre survival from breast cancer improved markedly from 1992 to 2005.
      Breast cancer prognosis was influenced by both clinical and organisational
      variables. The quantification of the role of such factors affords valuable
      knowledge to improve cancer care in settings similar to the study hospital.

PMID- 22854423
TI  - A survey of environmental service workers' knowledge and opinions regarding
      environmental cleaning.
AB  - Environmental service workers play an important role in the prevention of health
      care-associated infections. Environmental service workers working at a Veterans
      Administration Medical Center completed the Environmental Service Workers'
      Knowledge and Opinions Regarding Environmental Cleaning Survey. The findings from
      this survey suggest the need for further education of environmental service
      workers regarding the different types of pathogens that are spread by
      contaminated environmental surfaces and which of these are killed with bleach.

PMID- 22854424
TI  - Organ donation and Islam-challenges and opportunities.
AB  - The issue of organ donation in Islam has been debated for decades, with most
      religious authorities sanctioning both living-organ and deceased-organ donation.
      However, disquiet among the Islamic community on the compatibility of organ
      donation with their faith remains, especially in relation to deceased-organ
      donation. This remains a topical, controversial, and challenging component of
      organ procurement at both local and international levels. In this article, I will
      explore Islamic arguments both for and against organ donation, in the context of
      both living-donor and deceased-donor models. By discussing both practical and
      philosophical perspectives, the aim is to facilitate discussion on how best to
      achieve consensus on this issue by driving the debate forward in an open and all
      encompassing manner. Although every attempt should be made to achieve consensus
      among key Muslim opinion makers (individuals, authorities, and institutions),
      encouraging personalized decision making by intellectual effort should be the
      goal to achieve genuine informed consent.

PMID- 22854425
TI  - Impairment of long-term depression in the anterior cingulate cortex of mice with
      bone cancer pain.
AB  - The anterior cingulate cortex (ACC) has been shown to play an important role in
      pain-related perception and chronic pain. However, little is known about the
      molecular mechanisms involved. To address this issue, we analyzed excitatory
      synaptic transmission and long-term synaptic plasticity in layer II/III pyramidal
      neurons within the rostral ACC (rACC) from mice with bone cancer pain induced by
      intra-tibia implantation of osteolytic fibrosarcoma cells. Ex vivo whole-cell
      patch-clamp recordings from rACC neurons showed no significant alterations in
      presynaptic glutamate release probability and postsynaptic alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated synaptic responses in
      mice with bone cancer pain. However, mechanical allodynia occurred in conjunction
      with decreased N-methyl-d-aspartate (NMDA)/AMPA ratio of synaptic currents
      elicited in bilateral rACC neurons. In addition, the induction of NMDA receptor
      dependent long-term depression (LTD) at rACC synapses was impaired in rACC
      neurons of tumor-bearing mice. Western blot analysis revealed a significant
      decrease in the levels of NR1, NR2A, and NR2B subunits of NMDA receptors in the
      rACC under bone cancer pain condition. No significant changes in overall mRNA
      levels for any of the NMDA receptor subunits or calpain activity were observed in
      the rACC of tumor-bearing mice. These results indicate that tumor-induced injury
      or remodeling of primary afferent sensory nerve fibers that innervate the tumor
      bearing bone may cause a persistent decrease in NMDA receptor expression in rACC
      neurons, resulting in a loss of LTD induction, thereby leading to long-term
      alterations of rACC activity and creating exaggerated pain behaviors.

PMID- 22854427
TI  - How much ischaemia should be tolerated before recommending revascularization?

PMID- 22854426
TI  - Clinical practice and evaluation of electronic portal imaging device for VMAT
      quality assurance.
AB  - Volumetric-modulated arc therapy (VMAT) is a novel extension of the intensity
      modulated radiation therapy (IMRT) technique, which has brought challenges to
      dose verification. To perform VMAT pretreatment quality assurance, an electronic
      portal imaging device (EPID) can be applied. This study's aim was to evaluate
      EPID performance for VMAT dose verification. First, dosimetric characteristics of
      EPID were investigated. Then 10 selected VMAT dose plans were measured by EPID
      with the rotational method. The overall variation of EPID dosimetric
      characteristics was within 1.4% for VMAT. The film system serving as a
      conventional tool for verification showed good agreement both with EPID
      measurements ([94.1 +/- 1.5]% with 3 mm/3% criteria) and treatment planning
      system (TPS) calculations ([97.4 +/- 2.8]% with 3 mm/3% criteria). In addition,
      EPID measurements for VMAT presented good agreement with TPS calculations ([99.1
      +/- 0.6]% with 3 mm/3% criteria). The EPID system performed the robustness of
      potential error findings in TPS calculations and the delivery system. This study
      demonstrated that an EPID system can be used as a reliable and efficient quality
      assurance tool for VMAT dose verification.

PMID- 22854428
TI  - Regularizing the approach to the irregularly irregular.

PMID- 22854429
TI  - Synthetic legal intoxicating drugs (April 2012).

PMID- 22854430
TI  - Geriatric patient-centered medical home (May 2012).

PMID- 22854431
TI  - An argument for reviving the disappearing skill of cardiac auscultation.

PMID- 22854432
TI  - The stethoscope as metaphor.

PMID- 22854433
TI  - Distinguishing cellulitis from its mimics.
AB  - Distinguishing true cellulitis from its many imitators is challenging but
      critical if we are to avoid unnecessary use of antibiotics and delays in
      treatment. Common imitators of cellulitis are stasis dermatitis,
      lipodermatosclerosis, contact dermatitis, lymphedema, eosinophilic cellulitis,
      and papular urticaria. Specific criteria do not exist for the diagnosis of
      cellulitis, but the alert physician can find clues in the history and physical
      examination that point toward cellulitis.

PMID- 22854434
TI  - Atrial fibrillation: new drugs, devices, and procedures.
AB  - The way atrial fibrillation is managed has changed in recent years. Although new
      anticoagulants are available and more are coming, they offer only marginal
      benefit over warfarin (Coumadin) and have the disadvantages that their levels
      cannot be monitored and that their effect cannot be reversed rapidly if bleeding
      develops. Attempts should be made To Whom It May Concern: control symptomatic
      atrial fibrillation, first with antiarrhythmic drugs, then with radiofrequency
      ablation or with a combination. Ablation can be repeated for fibrillation that
      persists after the first few months.

PMID- 22854435
TI  - Genetic counselors: your partners in clinical practice.
AB  - As our understanding of the human genome has grown, so too has the need for
      health care providers who can help patients and families understand the
      implications of these new discoveries for their health care. Increasingly,
      genetic counselors are working in partnership with physicians to provide a
      continuum of care from risk assessment to diagnosis. In this article, we explain
      the process of genetic counseling and its value for patients who have a personal
      or family history of a hereditary condition.

PMID- 22854436
TI  - Autoinflammatory syndromes: fever is not always a sign of infection.
AB  - Autoinflammatory syndromes are a newly understood group of conditions
      characterized by recurrent episodes of fever, rash, and serositis. Generalists
      and specialists should know about and consider these syndromes in the
      differential diagnosis of recurrent fever. This article reviews the genetics,
      pathophysiology, clinical presentation, and treatment of several of these
      relatively recently discovered diseases.

PMID- 22854437
TI  - Induction of apoptosis and growth arrest in human breast carcinoma cells by a
      snake (Walterinnesia aegyptia) venom combined with silica nanoparticles:
      crosstalk between Bcl2 and caspase 3.
AB  - We recently demonstrated that the snake venom extracted from Walterinnesia
      aegyptia (WEV) either alone or combined with silica nanoparticles (WEV+NP)
      enhanced the proliferation of mice immune cells and simultaneously decreased the
      proliferation of human breast carcinoma cell line (MDA-MB-231). However, the
      molecular mechanism of how this venom induced growth arrest of breast cancer
      cells has not been studied. In this context, we extended our study to evaluate
      the anti-tumor potential of WEV and WEV+NP on the human breast carcinoma cell
      lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal
      breast epithelial cells (MCF-10). The IC(50 )values of WEV alone and WEV+NP in
      these cell lines were determined to be 50 ng/ml and 20 ng/ml, respectively.
      Interestingly, at these concentrations, the venom did not affect the viability of
      normal MCF-10 cells and treatment of all these cell lines with NP alone did not
      affect their viability. Using annexin-V binding assay followed by flow cytometry
      analysis, we found that combination of WEV with NP strongly induced apoptosis in
      MDA-MB-231 and MCF-7 cancer cells without significant effect on normal MCF-10
      cells. Furthermore, we found that WEV+NP decreased the expression of Bcl2 and
      enhanced the activation of caspase 3 in MDA-MB-231 and MCF-7 cells. Most
      importantly, WEV+NP-treated breast cancer cells, but not normal MCF-10 cells,
      exhibited a significant (P<0.05) reduction in actin polymerization and
      cytoskeletal rearrangement in response to CXCL12. Our data reveal biological
      effects of WEV or WEV+NP and the underlying mechanisms to fight breast cancer
      cells.

PMID- 22854438
TI  - Epigenetic reprogramming of Yak iSCNT embryos after donor cell pre-treatment with
      oocyte extracts.
AB  - The treatment of donor cells with oocyte extracts before inter-species somatic
      cell nuclear transfer (iSCNT) is a novel method for cellular reprogramming. This
      study aims to evaluate the effect of pre-treatment donor cell with oocyte
      extracts on the early developmental competence of yak iSCNT embryos. Yak
      fibroblasts were reversibly permeabilized with streptolysin O, and then treated
      with yak oocyte extracts (YOE) or bovine oocyte extracts (BOE) prior to iSCNT.
      The 8-cell and blastocyst formation increased significantly compared with the
      control group (P<0.05) when donor cells pre-treated with YOE or BOE. The relative
      expression level of embryo-specific genes TBP1 and Mash2 were also up-regulated
      both in the blastocysts of the YOE and BOE groups. In addition, the methylation
      level of pluripotency-specific genes (Oct4 and Nanog) in the blastocysts of the
      YOE and BOE groups were similar to that of its IVF counterpart (53.1%, 48.8% vs.
      40.1%; 24.8%, 26.5% vs. 35.9%). Our results suggested that pre-treatment of donor
      cells with oocyte extracts can improve nuclear-cytoplasmic reprogramming; thus
      representing a novel way to improve the efficiency of yak iSCNT.

PMID- 22854440
TI  - Long range plasmon assisted all-optical switching at telecommunication
      wavelengths.
AB  - We exploit the properties of ultranarrow, Fano-like resonances generated by the
      coupling of long range surface plasmons with ultrathin (~10 nm), metallic,
      subwavelength gratings embedded in a nonlinear, cubic material to obtain all
      optical switching at telecommunication wavelengths for extremely low input power.
      We provide an example of a silver metallic grating embedded in a chalcogenide
      glass (As2S3), and we show the concrete possibility to achieve all-optical
      switching at local field intensities compatible with the photo-darkening
      threshold of the material.

PMID- 22854439
TI  - Intake of liquid and solid sucrose in relation to changes in body fatness over 6
      years among 8- to 10-year-old children: the European Youth Heart Study.
AB  - OBJECTIVE: To examine if intake of soft drinks is more closely associated with
      weight gain than other energy sources and if these associations are mediated
      through differences in energy intake or insulin level. METHODS: Data derived from
      the Danish part of the European Youth Heart Study (n = 359). Height, weight, and
      waist circumference (WC) were measured in 1997-1998 and again in 2003-2004.
      RESULTS: Intake of liquid sucrose was associated with changes in waist
      circumference (DeltaWC) (beta = 0.226, p = 0.07, R(2) = 0.17) as well as BMI z
      scores (DeltaBMI(z)) (beta = 0.031, p = 0.05, R(2) = 0.30). Associations
      attenuated slightly after adjusting for energy intake, but were substantially
      reduced when adjusting for insulin. Adjustment for both insulin and energy intake
      attenuated the effect of soft drinks intake on DeltaBMI(z), but not on DeltaWC.
      CONCLUSION: Liquid sucrose seemed more clearly associated with DeltaWC and
      DeltaBMI(z) than other energy sources. For DeltaWC, the association seemed to be
      based on decreases in insulin sensitivity rather than increases in energy intake,
      whereas for DeltaBMI(z) the association seemed to be based on both increases in
      energy intake and decreases in insulin sensitivity.

PMID- 22854441
TI  - Omnidirectional emission from top-emitting organic light-emitting devices with
      microstructured cavity.
AB  - We demonstrate optimized viewing-angle characteristics from top-emitting organic
      light-emitting devices by integrating a periodic microstructure into the cavity.
      A holographic lithography technique combined with filling process of the groove
      by spin coating of a polymer film has been employed to enable its periodically
      and gradually changed cavity length and suppress the viewing-angle dependence of
      the peak emission wavelength and intensity. The theoretical and experimental
      results support that the proposed microstructured cavity can resolve the angular
      dependence effect in a very simple and effective way, and a desired
      omnidirectional emission has been obtained.

PMID- 22854442
TI  - Time-division multiplexing of the orbital angular momentum of light.
AB  - We present an optical setup for generating a sequence of light pulses in which
      the orbital angular momentum (OAM) degree of freedom is correlated with the
      temporal one. The setup is based on a single q plate within a ring optical
      resonator. By this approach, we demonstrate the generation of a train of pulses
      carrying increasing values of OAM, or, alternatively, of a controlled temporal
      sequence of pulses having prescribed OAM superposition states. Finally, we
      exhibit an "OAM-to-time conversion" apparatus that divides different input OAM
      states into different time bins. The latter application provides a simple
      approach to digital spiral spectroscopy of pulsed light.

PMID- 22854443
TI  - Black-light continuum generation in a silica-core photonic crystal fiber.
AB  - We report the observation of a broadband continuum spanning from 350 to 470 nm in
      the black-light region of the electromagnetic spectrum as a result of picosecond
      pumping a solid-core silica photonic crystal fiber at 355 nm. This was achieved
      despite strong absorption and a large normal dispersion of silica glass in the
      UV. Further investigations reveal that the continuum generation results from the
      interplay of intermodally phase-matched four-wave mixing and cascaded Raman
      scattering. We also discuss the main limitations in terms of bandwidth and power
      due to temporal walk-off, fiber absorption, and the photo darkening effect, and
      we suggest simple solutions.

PMID- 22854444
TI  - High-sensitivity Fabry-Perot interferometric pressure sensor based on a nanothick
      silver diaphragm.
AB  - We present a fiber-optic extrinsic Fabry-Perot interferometer pressure sensor
      based on a nanothick silver diaphragm. The sensing diaphragm, with a thickness
      measured in a few hundreds of nanometers, is fabricated by the electroless
      plating method, which provides a simple fabrication process involving a high
      quality diaphragm at a low cost. The sensor exhibits a relatively linear response
      within the pressure variation range of 0-50 kPa, with a high pressure sensitivity
      of 70.5 nm/kPa. This sensor is expected to have potential applications in the
      field of highly sensitive pressure sensors.

PMID- 22854445
TI  - Injection-seeded, gain-switched tunable Cr:ZnSe laser.
AB  - We report a narrow-linewidth, tunable, gain-switched Cr:ZnSe laser operating
      between 2255 and 2455 nm. The spectral width of the laser was reduced from 125 nm
      to 0.3 nm by using injection seeding. Seeding was achieved with a second tunable
      CW Cr:ZnSe laser. The output wavelength was varied by tuning the wavelength of
      the seed laser. The seeded oscillator produced as high as 157 uJ pulses with 598
      uJ incident pump pulse energy at a repetition rate of 1 kHz. The slope efficiency
      was determined to be 26%.

PMID- 22854446
TI  - Three-dimensional study of planar optical antennas made of split-ring
      architecture outperforming dipole antennas for increased field localization.
AB  - Optical antennas are of fundamental importance for the strongly localizing field
      beyond the diffraction limit. We report that planar optical antennas made of
      split-ring architecture are numerically found in three-dimensional simulations to
      outperform dipole antennas for the enhancement of localized field intensity
      inside their gap regions. The computational results (finite-difference time
      domain) indicate that the resulting field localization, which is of the order of
      many thousandfold, in the case of the split-ring resonators is at least 2 times
      stronger than the one in the dipole antennas resonant at the same operating
      wavelength, while the two antenna types feature the same gap size and tip
      sharpness.

PMID- 22854447
TI  - Quantum memory in warm rubidium vapor with buffer gas.
AB  - The realization of quantum memory using warm atomic vapor cells is appealing
      because of their commercial availability and the perceived reduction in
      experimental complexity. In spite of the ambiguous results reported in the
      literature, we demonstrate that quantum memory can be implemented in a single
      cell with buffer gas using the geometry where the write and read beams are nearly
      copropagating. The emitted Stokes and anti-Stokes photons display cross
      correlation values greater than 2, characteristic of quantum states, for delay
      times up to 4 MUs.

PMID- 22854448
TI  - Standoff detection of large organic molecules using Rydberg fingerprint
      spectroscopy and microwave Rayleigh scattering.
AB  - We present a technique for nonintrusive and standoff detection of large organic
      molecules using coherent microwave Rayleigh scattering from plasma produced by
      structure sensitive photoionization through Rydberg states. We test the method on
      1,4-diazobicyclooctane. Transitions between the 3s Rydberg state and higher lying
      Rydberg states are probed using two-color photoionization with 266 nm photons and
      photons in the range of 460-2400 nm. Photoionization is detected using microwave
      radiation, which is scattered by the unbounded electrons. Highly resolved Rydberg
      spectra are acquired in vacuum and in air.

PMID- 22854449
TI  - Spatial-carrier phase-shifting digital holography utilizing spatial frequency
      analysis for the correction of the phase-shift error.
AB  - We propose a single-shot digital holography in which the complex amplitude
      distribution is obtained by spatial-carrier phase-shifting (SCPS) interferometry
      and the correction of the inherent phase-shift error occurred in this
      interferometry. The 0th order diffraction wave and the conjugate image are
      removed by phase-shifting interferometry and Fourier transform technique,
      respectively. The inherent error is corrected in the spatial frequency domain.
      The proposed technique does not require an iteration process to remove the
      unwanted images and has an advantage in the field of view in comparison to a
      conventional SCPS technique.

PMID- 22854450
TI  - Phase correlations and optical coherence.
AB  - We examine the properties of the recently introduced degrees of coherence
      regarding the phase correlations of the optical field. It is seen that some of
      these quantities are straightforwardly related to the limits of complete
      dependence and complete independence of phases, which were used as the extremes
      of complete coherence and complete incoherence by Zernike in 1938. Certain other
      coherence measures are not in agreement with these limits in all situations. Our
      results elucidate the physical meaning of coherence in electromagnetic fields.

PMID- 22854451
TI  - Experimental demonstration of terahertz metamaterial absorbers with a broad and
      flat high absorption band.
AB  - We present the design, numerical simulations and experimental measurements of
      terahertz metamaterial absorbers with a broad and flat absorption top over a wide
      incidence angle range for either transverse electric or transverse magnetic
      polarization depending on the incident direction. The metamaterial absorber unit
      cell consists of two sets of structures resonating at different but close
      frequencies. The overall absorption spectrum is the superposition of individual
      components and becomes flat at the top over a significant bandwidth. The
      experimental results are in excellent agreement with numerical simulations.

PMID- 22854452
TI  - Plasmonic properties of aluminum nanorings generated by double patterning.
AB  - In this Letter we evaluate a technique for the efficient and flexible generation
      of aluminum nanorings based on double patterning and variable shaped electron
      beam lithography. The process is demonstrated by realizing nanorings with
      diameters down to 90 nm and feature sizes of 30 nm utilizing a writing speed of
      one ring per microsecond. Because of redepositions caused by involved etching
      processes, the material of the rings and, therefore, the impact on the plasmonic
      properties, are unknown. This issue, which is commonly encountered when metals
      are nanostructured, is solved by adapting a realistic simulation model that
      accounts for geometry details and effective material properties. Based on this
      model, the redepositions are quantified, the plasmonic properties are
      investigated, and a design tool for the very general class of nanofabrication
      techniques involving the etching of metals is provided.

PMID- 22854453
TI  - Wavelength separation from extreme ultraviolet mirrors using phaseshift
      reflection.
AB  - A generic design and fabrication scheme of Mo/Si multilayer-grating phaseshift
      reflector systems is reported. Close to optimized extreme ultraviolet (EUV,
      lambda=13.5 nm) reflectance values up to 64% are demonstrated, while the
      diffractive properties can be exploited in spectral filtering applications. The
      results can contribute to a wavelength-unspecific solution for the suppression of
      lambda>100 nm out-of-band radiation in EUV lithography.

PMID- 22854454
TI  - Toward single-molecule detection with sensors based on propagating surface
      plasmons.
AB  - Surface plasmon resonance (SPR) sensors are known to be able to detect very low
      surface concentrations of (bio)molecules on macroscopic areas. To explore the
      potential of SPR biosensors to achieve single-molecule detection, we have
      minimized the read-out area (to ~64 MUm2) by employing a sensor system based on
      spectroscopy of surface plasmons generated on a diffractive structure via a
      microscope objective and light collection through a small aperture. This approach
      allows for decreasing the number of detected molecules by 3 orders of magnitude
      compared to state-of-the-art SPR sensors. A protein monolayer has been shown to
      produce a response of 5000 times the baseline noise, suggesting that as few as
      ~500 proteins could be detected by the sensor.

PMID- 22854455
TI  - Brillouin-assisted microwave frequency measurement with adjustable measurement
      range and resolution.
AB  - We present a reconfigurable microwave frequency measurement technique with
      adjustable measurement range and resolution. The key novelty of the technique is
      the employment of stimulated Brillouin scattering, which results in a tunable
      amplitude comparison function, leading to an adjustable measurement range and
      resolution. The proposed technique is switchable between a wideband tunable
      narrow measurement range (~2 GHz) with high resolution (+/-0.05 GHz) and a fixed
      wide measurement range (12 GHz) with moderate resolution (+/-0.25 GHz).

PMID- 22854456
TI  - Coherent-mode representation of supercontinuum.
AB  - We apply the coherent-mode expansion to correlation functions used to describe
      the coherence properties of supercontinuum generated in nonlinear fibers. We show
      that the leading term of the expansion represents the quasi-coherent part of the
      field while the quasi-stationary part is embedded into the higher-order modes.
      The evolution of the modal expansion and the number of modes needed to describe
      the supercontinuum field are also discussed.

PMID- 22854457
TI  - Deterministic qubit transfer between orbital and spin angular momentum of single
      photons.
AB  - In this work we experimentally implement a deterministic transfer of a generic
      qubit initially encoded in the orbital angular momentum of a single-photon to its
      polarization. Such a transfer of quantum information, which is completely
      reversible, has been implemented adopting an electrically tunable q-plate device
      and a Sagnac interferometer with a Dove prism. The adopted scheme exhibits high
      fidelity and low losses.

PMID- 22854458
TI  - Impact of slow gain dynamics on soliton molecules in mode-locked fiber lasers.
AB  - We theoretically demonstrate and experimentally confirm the major influence of
      gain dynamics on soliton molecules that self-assemble in mode-locked lasers. Both
      slow gain recovery and depletion play a pivotal role in the formation of chirped
      soliton molecules characterized by an increasing separation from leading to
      trailing pulses. These chirped molecules actually consist of many pulses and may
      be termed macromolecules. They are experimentally observed in a fiber laser and
      numerically modeled by an approach that properly includes the slow gain dynamics.
      Furthermore, it is shown that these processes stabilize soliton trains in fiber
      lasers by inhibiting internal oscillations.

PMID- 22854459
TI  - Beam tracing approach of 2*2 extended Jones matrix method for stratified uniaxial
      structures.
AB  - In compliance with the commonly adopted small anisotropy approximation, a beam
      tracing modeling of a 2*2 extended Jones matrix algorithm is proposed, which
      traces the phase retardation along the geometric beam path, instead of along the
      normal direction, as the light beam is propagating through a stratified
      anisotropic structure. Consequently, polarization transformation at interfaces of
      the structure is unified by rotational operations of the coordinate system for
      light waves incident at both normal and oblique angles. Numerical simulations on
      optical transmittance demonstrate rational and consistent results with respect to
      currently prevailing algorithms.

PMID- 22854460
TI  - Photonic generation of stable microwave signals from a dual-wavelength Al2O3:Yb3+
      distributed-feedback waveguide laser.
AB  - We report the fabrication and characterization of a dual-wavelength distributed
      feedback channel waveguide laser in ytterbium-doped aluminum oxide. Operation of
      the device is based on the optical resonances that are induced by two local phase
      shifts in the distributed-feedback structure. A stable microwave signal at ~15
      GHz with a -3 dB width of 9 kHz was subsequently created via the heterodyne
      photodetection of the two laser wavelengths. The long-term frequency stability of
      the microwave signal produced by the free-running laser is better than +/-2.5
      MHz, while the power of the microwave signal is stable within +/-0.35 dB.

PMID- 22854461
TI  - Twist phase-induced reduction in scintillation of a partially coherent beam in
      turbulent atmosphere.
AB  - The scintillation index of a Gaussian Schell-model beam with twist phase (i.e.,
      twisted GSM beam) in weak turbulent atmosphere is formulated with the help of a
      tensor method. Variations of the scintillation index of a twisted GSM beam on
      propagation in turbulent atmosphere are studied in detail. It is interesting to
      find that the scintillation index of a twisted GSM beam can be smaller than that
      without twist phase in weak turbulent atmosphere. Thus, modulation of the twist
      phase of a partially coherent beam provides a new way to reduce turbulence
      induced scintillation.

PMID- 22854462
TI  - Asynchronous midinfrared ultrafast optical parametric oscillator for dual-comb
      spectroscopy.
AB  - Two asynchronous, broadband 3.3 um pulse trains with a stabilized repetition-rate
      difference of up to 5 kHz were generated using an ultrafast optical parametric
      oscillator. The two oscillation channels, each producing ~100 mW average power,
      ran essentially independently, and weak non-phase-matched sum-frequency mixing
      between them provided a timing signal that indicated when the asynchronous pulses
      coincided. The system has immediate applications in incoherent asynchronous
      optical sampling and, with additional carrier-envelope-offset stabilization,
      could be applied to coherent dual-frequency-comb spectroscopy.

PMID- 22854463
TI  - Periodic nanostructures on Si(100) surfaces generated by high-repetition rate sub
      15 fs pulsed near-infrared laser light.
AB  - Nanoscale rifts and ripples at a periodicity of 130 nm were generated on Si(100)
      surfaces immersed in water using tightly focused 800 nm 12 fs pulsed 85 MHz laser
      light at subnanojoule pulse energies. At radiant exposure close to the ablation
      threshold rifts were typically 20-50 nm in width and 70 nm in depth running
      perpendicular to the laser polarization. On increase of the irradiance, the rifts
      broadened and formed periodic ripples, whereas at highest exposure, a random
      nanoporous surface topology emerged. Rift and ripple formation is explained by
      laser-induced standing surface plasma waves, which result in periodic variation
      of dissipation and ablation.

PMID- 22854464
TI  - Perfectly notched long-period fiber grating filter based on ICP dry etching
      technique.
AB  - This study presents a new process using inductively a coupled plasma dry etching
      method to manufacture a long-period fiber grating filter with exact period,
      vertical sidewalls, and smooth etched surfaces, and the filter is thus named a
      perfectly notched long-period fiber grating (NLPFG). This process can
      dramatically reduce production time, and thereby provide higher volume
      production. The fabricated NLPFG has periods of 640 MUm, resonant-attenuation
      wavelengths of 1518 nm, and maximum resonance-attenuation of 21.79 dB. A force
      induced loss-tunable calibration of the NLPFG filter was implemented, and a
      monotonically increasing quadratic fitting was observed. The results demonstrated
      that the proposed NLPFG has a much better period precision compared to corrugated
      LPFG, and it has great potential for a loss-tunable filter and force transducer
      applications.

PMID- 22854465
TI  - Wideband tunable laser phase noise reduction using single sideband modulation in
      an electro-optical feed-forward scheme.
AB  - A wideband laser phase noise reduction scheme is introduced where the optical
      field of a laser is single sideband modulated with an electrical signal
      containing the discriminated phase noise of the laser. The proof-of-concept
      experiments on a commercially available 1549 nm distributed feedback laser show
      linewidth reduction from 7.5 MHz to 1.8 kHz without using large optical cavity
      resonators. This feed-forward scheme performs wideband phase noise cancellation
      independent of the light source and, as such, it is compatible with the original
      laser source tunability without requiring tunable optical components. By placing
      the proposed phase noise reduction system after a commercial tunable laser, a
      tunable coherent light source with kilohertz linewidth over a tuning range of
      1530-1570 nm is demonstrated.

PMID- 22854466
TI  - Quantitative surface normal measurement by a wavefront camera.
AB  - A compact wavefront camera that allows users to quantitatively measure the
      intensity and wavefront at a remote object plane is reported. The camera is built
      from a chip-scale wavefront sensor that we previously developed. By measuring the
      wavefront of the image and calibrating the wavefront relationship between the
      image and object planes, the wavefront at the object plane can be computed and
      the surface normal of the object can be derived. We built a prototype camera and
      calibrated the wavefront relationship. In a proof-of-concept experiment, a set of
      concave mirrors with different focal lengths (50-200 mm), were imaged. The
      results agree well with their expected values. To demonstrate the application of
      the camera, we applied this method to measure the deformation of a microfluidic
      channel under pressure.

PMID- 22854467
TI  - High precision micro-displacement fiber sensor through a suspended-core Sagnac
      interferometer.
AB  - A sensing system for micro-displacement measurement based in a suspended-core
      fiber Sagnac interferometer is presented. The suspended-core fiber
      characterization was made through the use of an optical backscatter
      reflectometer, screening its multimodal and birefringent behavior. Its
      sensitivity to displacement measurements is shown to be due only to
      birefringence, being that core-cladding mode coupling is negligible. High
      precision (~0.45 MUm) was obtained using three different measurement instruments,
      showing an extremely high stability and high insensitivity to temperature,
      demonstrating that the sensing system has the ability for low cost applications.

PMID- 22854468
TI  - Intense red upconversion luminescence from Tm3+/Yb3+ codoped transparent glass
      ceramic.
AB  - Tm3+/Yb3+ codoped transparent glass ceramic containing beta-PbF2 nanocrystals was
      successfully prepared. After thermal treatment, emissions from the state of Tm3+
      excited by 980 nm laser were greatly quenched by cross relaxation and the 700 nm
      luminescence from Tm3+:3F2,3->3H6 transition was strongly enhanced. A nearly
      monochromatic red luminescence band was observed. Based on the luminescence decay
      curves and Judd-Ofelt analysis, the strengthened cross relaxation played an
      important role in such phenomenon.

PMID- 22854469
TI  - Tailored pulse sequences from an 880 nm pumped Nd:YVO4 bounce amplifier.
AB  - We report on an 880 nm quasi-continuously pumped Nd:YVO4 grazing-incidence
      "bounce" amplifier, operating at a 300 Hz repetition rate. More than 70 dB small
      signal gain is achieved with a single crystal. Combined with fast programmable
      modulators, high-contrast and near-diffraction-limited pulse sequences at the 100
      MUJ level are produced and can be tailored in terms of pulse duration, amplitude,
      and a temporal spacing well into the microsecond range. This system could
      significantly improve extreme-UV comb generation based on parametric
      amplification and harmonic upconversion of two near-IR comb laser pulses.

PMID- 22854470
TI  - Effective control of photoluminescence from ZnO nanowires by a-SiNx:H decoration.
AB  - The a-SiNx:H with a large bandgap of 3.8 eV was utilized to decorate ZnO
      nanowires. The UV emission from the a-SiNx:H-decorated ZnO nanowires are greatly
      enhanced compared with the undecorated ZnO nanowire. The deep-level defect
      emission has been completely suppressed even though the sample was annealed at
      temperatures up to 400  degrees C. The incorporation of H and N is suggested to
      passivate the defect states at the nanowire surface and thus result in the flat
      band effect near ZnO surface as well as reduction of the nonradiative
      recombination probability.

PMID- 22854471
TI  - Evanescent-wave photoacoustic spectroscopy with optical micro/nano fibers.
AB  - We demonstrate gas detection based on evanescent-wave photoacoustic (PA)
      spectroscopy with tapered optical fibers. Evanescent-field instead of open-path
      absorption is exploited for PA generation, and a quartz tuning fork is used for
      PA detection. A tapered optical fiber with a diameter down to the wavelength
      scale demonstrates detection sensitivity similar to an open-path system but with
      the advantages of easier optical alignment, smaller insertion loss, and
      multiplexing capability.

PMID- 22854472
TI  - Terahertz tomography using quantum-cascade lasers.
AB  - The interfaces of a dielectric sample are resolved in reflection geometry using
      light from a frequency agile array of terahertz quantum-cascade lasers. The
      terahertz source is a 10-element linear array of third-order distributed-feedback
      QCLs emitting at discrete frequencies from 2.08 to 2.4 THz. Emission from the
      array is collimated and sent through a Michelson interferometer, with the sample
      placed in one of the arms. Interference signals collected at each frequency are
      used to reconstruct an interferogram and detect the interfaces in the sample.
      Because of the long coherence length of the source, the interferometer arms need
      not be adjusted to the zero-path delay. A depth resolution of 360 um in the
      dielectric is achieved with further potential improvement through improved
      frequency coverage of the array. The entire experiment footprint is <1 m * 1 m
      with the source operated in a compact, closed-cycle cryocooler.

PMID- 22854473
TI  - Differential and product Mueller matrix decompositions: a formal comparison.
AB  - It is shown that the Mueller matrix logarithm and the Mueller matrix roots
      decompositions used for the extraction of the elementary polarization properties
      of a depolarizing medium, although being computationally different, are formally
      equivalent, being both based upon the differential representation of a
      continuously depolarizing medium. The common set of six elementary polarization
      properties provided by these two decompositions is generally different from that
      obtained from the various product decompositions summarized by the G-polar
      decomposition whereby the depolarization phenomenon is treated as being
      concentrated, and not uniformly distributed, within the medium. However, if the
      medium is weakly depolarizing, the two sets of elementary properties coincide to
      the first order in the depolarization and tend to the set of properties of the
      nondepolarizing estimate of the measured Mueller matrix obtained from its Cloude
      sum decomposition.

PMID- 22854474
TI  - High-speed wavelength-division multiplexing quantum key distribution system.
AB  - A high-speed quantum key distribution system was developed with the wavelength
      division multiplexing (WDM) technique and dedicated key distillation hardware
      engines. Two interferometers for encoding and decoding are shared over eight
      wavelengths to reduce the system's size, cost, and control complexity. The key
      distillation engines can process a huge amount of data from the WDM channels by
      using a 1 Mbit block in real time. We demonstrated a three-channel WDM system
      that simultaneously uses avalanche photodiodes and superconducting single-photon
      detectors. We achieved 12 h continuous key generation with a secure key rate of
      208 kilobits per second through a 45 km field fiber with 14.5 dB loss.

PMID- 22854475
TI  - Polarization-dependent ablation of silicon using tightly focused femtosecond
      laser vortex pulses.
AB  - We demonstrate experimentally that, in a tight focusing geometry, circularly
      polarized femtosecond laser vortex pulses ablate material differently depending
      on the handedness of light. This effect offers an additional degree of freedom to
      control the shape and size of laser-machined structures on a subwavelength scale.

PMID- 22854476
TI  - High-spatial-resolution one-dimensional rotational coherent anti-Stokes Raman
      spectroscopy imaging using counterpropagating beams.
AB  - A counterpropagating phase-matching geometry is employed for high-spatial
      resolution one-dimensional (1D) imaging of temperature and O2-to-N2 concentration
      ratio using picosecond pure-rotational coherent anti-Stokes Raman spectroscopy
      (RCARS) over a large field (20 mm). A single-shot 1D RCARS image of more than 20
      mm in length is thus acquired at 300 K in air. High-resolution 1D RCARS flame
      measurements are demonstrated using a custom-built burner and a premixed
      methane/air flame (Phi=0.6). This phase-matching scheme improves the spatial
      resolution by approximately 1 order of magnitude when compared to the standard
      small-angle BOXCARS phase-matching schemes typically employed in CARS
      measurements. Additionally, for a 20 mm 1D image, signal levels are increased by
      10(2) because of the higher irradiance provided in the current scheme.

PMID- 22854477
TI  - Coupling loss minimization of slow light slotted photonic crystal waveguides
      using mode matching with continuous group index perturbation.
AB  - We experimentally demonstrate highly efficient coupling into a slow light slotted
      photonic crystal waveguide. With optical mode converters and group index tapers
      that provide good optical mode matching and impedance matching, a nearly flat
      transmission over the entire guided mode spectrum of 68.8 nm range with 2.4 dB
      minimum insertion loss is demonstrated. Measurements also show up to 20 dB
      baseline enhancement and 30 dB enhancement in the slow light region, indicating
      that it is possible to design highly efficient and compact devices that benefit
      from the slow light enhancement without increasing the coupling loss.

PMID- 22854478
TI  - Multiple color reflection in a single unit cell using double-layer electrochromic
      reaction.
AB  - Multiple color states have been realized in single unit cell using double
      electrochromic (EC) reaction. The precise control of bistability in EC compounds
      which can maintain several colors on the two separated electrodes allows this new
      type of pixel to be realized. The specific electrical driving gives a way to
      maintain both sides in the reduced EC states and this colors overlapping in the
      vertical view direction can achieve the black state. The four color states (G, B,
      W, BK) in one cell/pixel can make a valuable progress to achieve a high quality
      color devices such like electronic paper, outdoor billboard, smart window and
      flexible display using external light source.

PMID- 22854479
TI  - Efficient generation of isolated attosecond pulses with high beam quality by two
      color Bessel-Gauss beams.
AB  - The generation of isolated attosecond pulses with high efficiency and high beam
      quality is essential for attosecond spectroscopy. We numerically investigate the
      supercontinuum generation in a neutral rare-gas medium driven by a two-color
      Bessel-Gauss beam. The results show that an efficient smooth supercontinuum in
      the plateau is obtained after propagation and the spatial profile of the
      generated attosecond pulse is Gaussian-like with the divergence angle of 0.1
      degrees  in the far-field. This bright source with high beam quality is
      beneficial for detecting and controlling the microscopic processes on attosecond
      time scale.

PMID- 22854481
TI  - Guided-wave second harmonics in Nd:YCOB optical waveguides for integrated green
      lasers.
AB  - We report on guided-wave second-harmonic generations in nonlinear Nd:YCa4O(BO3)3
      (Nd:YCOB) optical waveguides that are produced by the low-fluence swift Ar8+ ion
      irradiation. The guided-wave second harmonics are realized through the frequency
      doubling and the self-frequency-doubling of the waveguides under the optical
      pumps at wavelengths of 1064 and 810 nm, respectively. By virtue of the self
      frequency-conversion configuration, the Nd:YCOB waveguides are promising
      candidates as novel, compact, miniature green laser sources.

PMID- 22854480
TI  - Temporal contrast enhancement of picosecond pulses based on phase-conjugate wave
      generation.
AB  - A practical technique based on the phase-conjugate wave (PCW) generation is
      proposed to improve the temporal contrast of the picosecond pulses. Our theory
      predicts the temporal contrast of the picosecond pulses can be enhanced to about
      the cube of the temporal contrast of the input pulse via the PCW generation, in
      which the conversion efficiency from the incident pulse to the PCW is about 25%.
      In a proof-of-principle experiment, the temporal contrast of picosecond pulses
      was enhanced from 1.7*10(3) to 8.6*10(8) with the conversion efficiency of 10%.
      This technique is promising to effectively eliminate the background of the
      ultrashort and ultraintense laser pulses in the future.

PMID- 22854482
TI  - Surface-plasmon-polaritons-assisted nanolithography with dual-wavelength
      illumination for high exposure depth.
AB  - We propose a new direct writing nanolithography approach using a plasmonic
      focusing device and a nano silver mirror with dual-wavelength illumination for
      high exposure depth. Arrays of pyramid aperture are used to focus the incident
      light beams into 80 nm light spots. The pyramid combined with a thin silver film
      coated on the substrate constructs a surface plasmon polaritons (SPP) coupling
      cavity, which amplifies the intensity of the light field in it by SPP effect and
      resonance. The transmission depth of the standing wave formed by forward and
      reflected light could reach hundreds of nanometers. Two lasers with different
      wavelengths are used as illumination sources to homogenize the light field
      through complementation between the two standing waves. Simulation results show
      by using 355 nm and 441 nm wavelengths, a space of 44 nm at the bottom of the
      photoresist could be obtained after exposure and development. The feature size of
      resist patterns could be further scaled down, depending on the optimization of
      parameters of photoresist exposure and development, illumination wavelengths,
      etc.

PMID- 22854483
TI  - Streak camera crosstalk reduction using a multiple delay optical fiber bundle.
AB  - The streak camera is one of the fastest photodetection systems, while its
      capability of multiplexing is particularly attractive to many applications
      requiring parallel data acquisition. The degree of multiplexing in a streak
      camera is limited by the crosstalk between input channels. We developed a
      technique that introducing a fixed time delay between adjacent fiber channels in
      a customized two-dimensional to one-dimensional fiber array to significantly
      reduce crosstalk both at the sample plane and at the input of a streak camera. A
      prototype system has been developed that supports 100 input channels, and its
      performance in fluorescence microscopy is demonstrated.

PMID- 22854484
TI  - Generation of megawatt peak power picosecond pulses from a divided-pulse fiber
      amplifier.
AB  - Control of nonlinearity is a challenge in fiber amplifiers designed to generate
      pulses of a few picoseconds duration, and as a result, picosecond fiber
      amplifiers have failed to reach peak power of 1MW. Divided-pulse amplification,
      combined with the use of circular polarization, allows the generation of 2.2 ps
      pulses with energy as high as 2.5 MUJ and peak power of 1 MW.

PMID- 22854485
TI  - Laser-written nanoporous silicon ridge waveguide for highly sensitive optical
      sensors.
AB  - We report that low-loss ridge waveguides are directly written on nanoporous
      silicon layers by using an argon-ion laser at 514 nm up to 100 mW. Optical
      characterization of the waveguides indicates light propagation loss lower than
      0.5 dB/cm at 1550 nm after oxidation. A Mach-Zehnder interferometer sensor is
      experimentally demonstrated using the waveguide in its sensing branch, and
      analytical results indicate that very high sensitivity can be achieved. With
      large internal surface area, versatile surface chemistry, and adjustable index of
      refraction of porous silicon, the ridge waveguides can be used to configure Mach
      Zehnder interferometers, Young's interferometers, and other photonic devices for
      highly sensitive optical biosensors and chemical sensors as well as other
      applications.

PMID- 22854486
TI  - Triggering and guiding high-voltage discharge in air by single and multiple
      femtosecond filaments.
AB  - The abilities to trigger and guide high-voltage discharge by using single and
      <em>multiple filaments</em> (MFs) are experimentally studied. It is shown that
      the discharge voltage threshold can be reduced significantly in both regimes of
      single and MF; however, the MF does not gain a larger reduction than a single
      filament. This behavior of the MF is attributed to the single discharge path
      rather than simultaneous multiple ones as one might expect during the discharge
      process.

PMID- 22854487
TI  - Iterative retrieval of one-dimensional x ray wave field using a single intensity
      measurement.
AB  - The problem of retrieving a complex function from the modulus of its Fourier
      transform has non-unique solutions in one dimension. Therefore iterative phase
      retrieval methods cannot in general be confidently applied to one-dimensional
      problems, due to the presence of ambiguities. We present a method for a
      posteriori reduction of the ambiguities based on the correlation analysis of the
      solution of a large number of runs of an iterative phase retrieval algorithm with
      different random starting phases. The method is applied to experimentally
      measured diffraction patterns from an x ray waveguide illuminated by hard x rays.
      We demonstrate the possibility of retrieving the complex wave field at the exit
      face of the waveguide and compare the result with theoretical prediction.

PMID- 22854488
TI  - Scattering of electromagnetic waves by charged spheres: near-field external
      intensity distribution.
AB  - This Letter treats the scattering of electromagnetic waves by an electrically
      charged spherical particle in near-field approximation. Particular attention is
      paid to the external intensity distribution at the outer edges of the particle.
      The difference between scattering by a charged sphere and an electrically neutral
      sphere is significant only when size parameters exceed unity.

PMID- 22854489
TI  - Intense 2.7 um emission and structural origin in Er3+-doped bismuthate (Bi2O3
      GeO2-Ga2O3-Na2O) glass.
AB  - The 2.7 MUm emission properties in Er3+-doped bismuthate (Bi2O3-GeO2-Ga2O3-Na2O)
      glass were investigated in the present Letter. An intense 2.7 MUm emission in
      Er3+-doped bismuthate glass was observed. It is found that Er3+-doped bismuthate
      glass possesses high spontaneous transition probability A (65.26 s(-1)) and large
      2.7 MUm emission cross section sigma(em) (9.53*10(-21) cm2) corresponding to the
      stimulated emission of Er3+:4I11/2->4I13/2 transition. The emission
      characteristic and energy transfer process upon excitation of a conventional 980
      nm laser diode in bismuthate glass were analyzed. Additionally, the structure of
      bismuthate glass was analyzed by the Raman spectrum. The advantageous
      spectroscopic characteristics of Er3+ single-doped bismuthate glass together with
      the prominent thermal property indicate that bismuthate glass might become an
      attractive host for developing solid-state lasers around 2.7 MUm.

PMID- 22854490
TI  - Wideband plasmonic beam steering in metal gratings.
AB  - We demonstrate controllable light deflection in thick metal gratings with
      periodic subwavelength slits filled with an active material. Under specific
      illumination conditions, the grating becomes nearly transparent and acts as a
      uniform optical phased-array antenna where the phase of the radiating elements is
      controlled by modifying the index of refraction of the material that fills each
      slit. The beam-steering operational regime occurs in a wide wavelength band, and
      it is relatively insensitive to the input angle.

PMID- 22854491
TI  - Optimized free-form optical trapping systems.
AB  - We report a comprehensive process for designing and prototyping new and optimized
      optical trapping systems. A combination of traditional lens design strategies,
      simulation of optical forces, and high-end ultraprecision machining of optical
      free-form surfaces is applied to the realization of a highly specialized optical
      trapping system. The resulting compact and lightweight optical modules
      potentially open new classes of applications for optical manipulation. As an
      example we present a customized 3D trapping module made of a single piece of
      polymethylmethacrylate, with a large working distance of 650 MUm.

PMID- 22854492
TI  - Ronchi-grating-based measurement of photorefractive recording response time.
AB  - We report on a simple technique for the measurement of the recording response
      time in photorefractive materials. Three different material samples were
      successfully measured, and their response times, as well as their dependence upon
      the recording/measurement light irradiance, were also determined and compared
      with available data in the literature in order to assess the reliability of this
      technique.

PMID- 22854493
TI  - Enhanced photonic crystal cavity-waveguide coupling using local slow-light
      engineering.
AB  - This Letter introduces an enhanced cavity-waveguide coupling architecture based
      upon slow-light engineering in a two-port photonic crystal system. After
      analyzing the system transmittance using coupled-mode theory, the system is
      probed experimentally and shown to have increased transmittance due to the
      enhanced cavity-waveguide coupling. Such a coupling architecture may facilitate
      next-generation planar lightwave circuitry such as onchip quantum information
      processing or high precision light-matter sensing applications.

PMID- 22854494
TI  - Laser profile reshaping in a Fabry-Perot thin film.
AB  - We report the observation of non-Gaussian reflected and transmitted laser spatial
      profiles resulting from the excitation of resonant modes below the critical angle
      for total reflection in a Fabry-Perot cavity formed by a thin ~7 um air film
      between two glass prisms. The observations of an interference minimum in the
      reflected profile and exponential decay in the transmitted profile are new and in
      excellent agreement with a complex pole theory. Extension of the theory to a
      larger ~0.7 m cavity at normal incidence predicts similar reshaped profiles.

PMID- 22854496
TI  - Cyclic glycolipids from glandular trichome exudates of Cerastium glomeratum.
AB  - Fourteen cyclic glycolipids, named glomerasides A-N, have been isolated from the
      glandular trichome exudate of Cerastium glomeratum (Caryophyllaceae). Their
      structures were determined by spectroscopic analysis of the glycolipids, as well
      as by application of the Ohrui-Akasaka method to the fatty acid methyl esters
      derived from the glycolipids and GCMS studies of trimethylsilyl ether derivatives
      of the methyl esters. The various glomerasides have a glycosidic linkage between
      the anomeric hydroxy group of the glucose and the C-11, C-10 or C-9 positions of
      the docosanoyl moiety. They also contained an ester linkage between the C-6
      hydroxy group of the glucose ring and the carboxyl group of the oxygenated fatty
      acid to form their macrocyclic structures. The glucose moiety was optionally
      acetylated and/or malonylated at the C-2 or C-3 hydroxy groups. Among these
      compounds, the 1,6'-cyclic ester of 11(R)-(2-O-acetyl-beta-d
      glucopyranosyloxy)docosanoic acid (glomeraside D) was the most abundant (25%).

PMID- 22854495
TI  - Increased arginase II activity contributes to endothelial dysfunction through
      endothelial nitric oxide synthase uncoupling in aged mice.
AB  - The incidence of cardiovascular disease is predicted to increase as the
      population ages. There is accumulating evidence that arginase upregulation is
      associated with impaired endothelial function. Here, we demonstrate that arginase
      II (ArgII) is upregulated in aortic vessels of aged mice and contributes to
      decreased nitric oxide (NO) generation and increased reactive oxygen species
      (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling.
      Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to
      that observed in young mice and increased NO generation and decreased ROS
      production. Furthermore, enhanced vasoconstrictor responses to U46619 and
      attenuated vasorelaxation responses to acetylcholine in aged vasculature were
      markedly improved following siRNA treatment against ArgII. These results might be
      associated with increased L-arginine bioavailability. Collectively, these results
      suggest that ArgII may be a valuable target in age-dependent vascular diseases.

PMID- 22854497
TI  - Lignans in seeds of Linum species.
AB  - Mature seeds of 20 Linum species were analyzed for their content of lignans. The
      seeds of common flax (Linum usitatissimum L.) are known to contain as
      characteristic lignan sesoisolariciresinol diglucoside (SDG), whose presence in
      seeds of some other Linum species has also been reported. In order to investigate
      the material for the presence of such very polar lignans as well as for less
      polar non-glycosidic lignans as frequently found in aerial parts of Linum
      species, polar and non-polar extracts of each sample were analyzed by HPLC/ESI
      MSMS. SDG was detected in 15 of 16 investigated seed samples of taxa representing
      sections Linum and Dasylinum. None of eight samples of taxa from sections
      Syllinum and Linopsis contained detectable amounts of SDG. Quite interestingly,
      most of the SDG-positive samples contained the 8R,8'R-isomer exclusively while
      only three (including L. usitatissimum) contained the 8S,8'S-stereoisomer as the
      predominant form. As a most noteworthy finding, the dichloromethane extracts
      obtained from seeds of several Linum species were found to contain significant
      concentrations of non-polar cyclolignans of the arylnaphthalene/
      dihydronaphthalene lactone type or, alternatively of the aryltetralin lactone
      type. Thus, seeds of Linum perenne L. as well as those of several other
      representatives of sections Linum and Dasylinum were found to contain significant
      concentrations of the arylnaphthalene justicidin B along with further compounds
      of this type and some aryldihydronaphthalene-type lignans. On the other hand,
      seeds of Linum flavum and further representatives of section Syllinum were found
      to contain aryltetralin-type lignans, mainly in the form of esters with aliphatic
      carboxylic acids, such as 6-methoxypodophyllotoxin-7-O-n-hexanoate, whose
      occurrence in L. flavum seeds has very recently been reported by us for the first
      time. Various chemosystematic and biogenetic aspects are discussed in the light
      of these results.

PMID- 22854498
TI  - [Beyond psychosis: the challenge of early intervention in bipolar disorders].

PMID- 22854499
TI  - [Imaging evidence for depression: is there biology in the bibliography?].

PMID- 22854500
TI  - [Recommendations for the prevention and management of suicidal behaviour].
AB  - INTRODUCTION: Suicidal behaviour is a major public health issue. Suicidal
      behaviour is one of the main causes of years of life lost and it is the third
      leading cause of death among young adults. This project was initiated by the
      Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry
      with the aim of providing a document containing the main recommendations on the
      prevention and management of suicidal behaviour; these recommendations should be
      based on the best available evidence and the experts' opinion. MATERIAL AND
      METHODS: In this article we summarize the review of the available evidence on the
      epidemiology and impact of suicidal behaviour, risk and protective factors,
      evaluation tools for the assessment of suicide risk, international and local
      preventive protocols, educational interventions for health professionals, and
      potential interventions for at risk populations. RESULTS: Based on this review, a
      panel of psychiatrists summarized and agreed a set of recommendations about the
      impact, prevention and management of suicidal behaviour. CONCLUSION: The
      recommendations on the prevention and management of suicidal behaviour were
      summarized in the ten conclusions reported in this article.

PMID- 22854501
TI  - [Brief Suicide Questionnaire. Inter-rater reliability].
AB  - INTRODUCTION: Inter-rater agreement is a crucial aspect in the planning and
      performance of a clinical trial in which the main assessment tool is the clinical
      interview. The main objectives of this study are to study the inter-rater
      agreement of a tool for the assessment of suicidal behavior (Brief Suicide
      Questionnaire) and to examine whether the inter-examiner agreement when multiple
      ratings are made on a single subject is an efficient method to assess the
      reliability of an instrument. METHOD: In the context of designing a multicenter
      clinical trial, 32 psychiatrists assessed a videotaped clinical interview of a
      patient with suicidal behavior. In order to identify those items in which a
      greater level of discordance existed and detect the examiners whose ratings
      differed significantly from the average ratings, we used the DOMENIC method
      (Detecion of Multiple Examiners Not in Consensus). RESULTS: Inter-rater agreement
      was between poor (<70%) to excelent (90-100%. Inter-rater agreement in Brugha's
      list of threatening experiences ranged from 75.5 and 100%; in the Global
      Assessment of Functioning (GAF) Scale was 82.58%; in the Beck's Suicidal Intent
      Scale, ranged from 67.5 and 97%; in the Beck's Scale for Suicide Ideation, ranged
      from 63.5 and 100%; and in the Lethality Rating Scale was 88.39%. On the whole,
      the level of agreement among raters, both in general scores and in particular
      items, was appropriate. CONCLUSION: The proposed design allows the assessment of
      the inter-rater agreement in an efficient way (only in one session). In addition,
      regarding the Brief Suicide Questionnaire, inter-raters agreement was
      appropriate.

PMID- 22854502
TI  - [Clozapine and agranulocitosis in Spain: do we have a safer population? A 5-year
      hematologic follow-up].
AB  - INTRODUCTION: Clozapine is an efective antipsychotic. However, its use has been
      associated with agranulocitosis. For this reason, it has been restricted for the
      treatment of resistant schizophrenia under a strict hematologic control. The
      objective of this work was to assess the risk of hematologic dyscrasias in a
      sample of clozapine-treated patients in a 5-year period. MATERIALS AND METHOD:
      This is a follow-up study in a cohort of clozapine-treated patients in which the
      risk of haematological dyscrasias was assessed. Complete blood cell count was
      made for each patient in a weekly basis for the first 18 weeks and thereafter
      monthly. RESULTS: 271 patients in treatment with clozapine were followed up. The
      mean age was 32.3 years, with 36.5% women. The mean dose was 227,6 mg, ranging
      from 25 to 600 mg/day. During the first 18 weeks of follow-up, we observed a 3%
      incidence of neutropenia and 1.3% of leucopenia. During the next two years, only
      one new case of neutropenia and leucopenia was observed (n=120). No new cases
      were observed during the rest of follow up (n=69). No cases of agranulocytosis
      were observed. CONCLUSIONS: A 3% incidence of neutropenia concentrated in the
      first months of follow up and no cases of agranulocitosis were observed in our
      sample. Actual evidence on clozapine effectiveness and safety and the results of
      this study suggests that a critical revision of follow-up protocols is suitable.

PMID- 22854503
TI  - [Relationship between insight, violence and diagnoses in psychotic patients].
AB  - INTRODUCTION: Lack of insight is a common clinical problem in psichiatric
      patients, but few times has been properly studied until recently. Patients with
      good insight tend to show a better treatment adherence with a better prognosis
      and swow less hostility. This study aims to investigate whether there is a
      relationship between the hostility degree and insight or not and to anlalyze if
      there are insight quantitative differences between the patients regarding their
      diagnoses. METHOD: 168 psychotic patients were studied (including 86 patients
      with schizophrenia and 43 with bipolar disorder). PANNS P7 (hostility) item and
      G14 (poor impulse control) were analized in order to assess patients' violence
      and G12 in order to assess insight. All these data was correlated. It was also
      analyzed the PANSS results of schizophrenic vs bipolar patients regarding insight
      and hostility separately looking for a more homogenic pull of patients. RESULTS:
      Patients with greater hostility showed a worse impulse control and poorer insight
      than the rest. Schizophrenic patients showed a greater hostility and lower
      insight than bipolar patients. DISCUSSION: Lack of insight may lead to a greater
      hostility and worse impulse control. Therapeutic interventions adressed to
      improve insight could indirectly lower hostility and gain a better impulse
      control for psychotic patients.

PMID- 22854504
TI  - [Lifestyle medicine: the importance of considering all the causes of disease].
AB  - The enormous potential effects of health behavior change on mortality, morbidity,
      and health care costs provide ample motivation for the concept of lifestyle
      medicine. Lifestyle medicine involves the therapeutic use of lifestyle
      interventions on health and quality of life, and considers not only risk factors
      and markers, but also a range of antecedent factors from all levels of causality.
      Treatment would ultimate employ a combination of clinical (patient-centered) and
      public-health interventions. Examples of target patient behaviors include, but
      are not limited to, eliminating tobacco use, moderating alcohol consumption,
      increasing physical activity, improving diet, sleep, and emotional and mental
      well-being. The effective implementation of lifestyle medicine should be a
      priority within the necessary changes in current healthcare systems and public
      health policies.

PMID- 22854505
TI  - [In defence of the diagnosis of simple schizophrenia: reflections on a case
      presentation].
AB  - INTRODUCTION: Since the first case descriptions of dementia praecox (Diem, 1903),
      the diagnosis of simple schizophrenia has continued to be controversial. The
      questioning of its descriptive validity and its reliability, as well as its
      infrequent use, has led to it being eliminated as a sub-type of schizophrenia in
      the DSM-III. Criteria for the diagnosis of "simple deteriorative disorder" are
      currently included in the DSM-IV-TR as a disorder requiring more studies for its
      possible inclusion. OBJECTIVES: An attempt is made, using a clinical case, to
      perform a historical review of the concept of simple schizophrenia, and at the
      same what has led to the reflection on the possible reasons for the controversy,
      and a potential route to resolve it. METHODOLOGY: Using a controversial clinical
      case, which meets ICD-10 clinical criteria for simple schizophrenia (and those of
      the DSM-IV-TR for the simple deteriorative disorder), we reflect on the symptoms
      and diagnostic difficulties. A literature review and update on the subjects was
      also performed. DISCUSSION: Our patient highlights, by the absence in the
      clinical picture of the most obvious positive psychotic symptoms, the tendency by
      psychiatrists to identify the diagnosis of schizophrenia with the presence of the
      same, at least at some time during its evolution. The use of neuroimaging tests
      was useful to assess the level of deterioration and prognosis of the patient.
      CONCLUSIONS: Considering simple schizophrenia in the differential diagnosis of
      other chronic deteriorative disorders could increase its recognition in the
      initial phases. The use of neuropsychological function tests, and looking for
      typical deteriorative patterns of the schizophrenia spectrum, could help to
      increase the reliability of the diagnosis.

PMID- 22854506
TI  - [Why don't we talk about negative psychotic symptoms in affective bipolar
      disorder?].

PMID- 22854507
TI  - The quality of life of people with dementia and their family carers.
AB  - BACKGROUND: We aimed to identify factors associated with the quality of life
      (QoL) of 'persons with dementia' (PWDs) and their family carers. METHOD: Two
      hundred and thirty dyads of PWDs and their family carers were included. The PWDs
      were assessed with the Neuropsychiatric Inventory (NPI-Q), two Activities of
      Daily Living (ADL) scales, the Cornell Scale and the QoL-Alzheimer's Disease
      scale (QoL-AD; self- and proxy-reported scores). The carers were assessed with
      the QoL-AD and the Geriatric Depression Scale. RESULTS: Factors associated with
      self-reported QoL were depression (beta = -0.26, p < 0.001) and impaired ADL
      (beta = -0.26, p < 0.001) and with proxy-rated QoL were NPI (beta = -0.18, p =
      0.02), depression (beta = -0.32, p < 0.001) and impaired ADL (beta = -0.43, p <
      0.001). Factors associated with QoL in carers living together with the PWDs were
      depression (beta = -0.56, p < 0.001) and having a hobby (beta = 0.19, p = 0.01),
      whereas depression was associated with QoL in those who lived separately from the
      PWD (beta = -0.60, p < 0.001). CONCLUSION: Depression and impaired ADL were
      associated with the self- and proxy-rated QoL of the PWDs, whereas depression in
      the carers negatively affected their QoL.

PMID- 22854508
TI  - Treatment of antineutrophil cytoplasmic antibody-associated vasculitis.
AB  - PURPOSE OF REVIEW: The primary idiopathic small-vessel vasculitis syndromes
      include granulomatosis with polyangiitis, Churg-Strauss syndrome, and microscopic
      polyangiitis. These disorders are commonly referred to as antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitides and prominently affect the
      pulmonary vasculature. Although significant progress has been made in the
      management of these disorders, they continue to carry substantial morbidity and
      mortality as a result of both the underlying vasculitis as well as complications
      of its immunosuppressive therapy. This review will focus on the recent advances
      in the management and longitudinal monitoring of ANCA-associated vasculitis.
      RECENT FINDINGS: Cyclophosphamide and glucocorticoids are standard therapy, but
      carry measureable risk of treatment-related toxicity. The search for alternative
      therapies that are less toxic but similarly efficacious is continuing. Recent
      investigations suggest rituximab may be a well tolerated alternative to
      cyclophosphamide for the induction of remission, treatment of disease relapse,
      and as maintenance therapy. SUMMARY: The ANCA-associated vasculitides are a group
      of disorders that commonly affect the pulmonary vasculature and represent a
      diagnostic and therapeutic challenge to the pulmonary clinician. Recent findings
      have expanded our ability to diagnose and treat these disorders with a focus on
      limiting treatment-related toxicity while inducing and maintaining remission.

PMID- 22854510
TI  - Current world literature.

PMID- 22854509
TI  - EMT and interstitial lung disease:  a mysterious relationship.
AB  - PURPOSE OF REVIEW: Pathogenesis of interstitial lung diseases (ILD) has largely
      been investigated in the context of the most frequent ILD, idiopathic pulmonary
      fibrosis (IPF). We review studies of epithelial-to-mesenchymal transition (EMT)
      and discuss its potential contribution to collagen-producing (myo)fibroblasts in
      IPF. RECENT FINDINGS: Endoplasmic reticulum (ER) stress leading to epithelial
      apoptosis has been reported as a potential etiologic factor in fibrosis. Recent
      studies further suggest EMT as a link between ER stress and fibrosis.
      Combinatorial interactions among Smad3, beta-catenin and other transcriptional co
      activators at the alpha-smooth muscle actin (alpha-SMA) promoter provide direct
      evidence for crosstalk between transforming growth factor-beta (TGFbeta) and beta
      catenin pathways during EMT. Lineage tracing yielded conflicting results, with
      two recent studies supporting and one opposing a role for EMT in lung fibrosis.
      SUMMARY: Advances have been made in elucidating causes and mechanisms of EMT,
      potentially leading to new treatment options, although contributions of EMT to
      lung fibrosis in vivo remain controversial. In addition to EMT providing a direct
      source of (myo)fibroblasts, expression of mesenchymal markers may reflect
      epithelial injury, in which case inhibition of EMT might be deleterious. EMT
      derived cells may also contribute to aberrant epithelial-mesenchymal crosstalk
      that promotes fibrogenesis.

PMID- 22854512
TI  - How can cobalamin injections be spaced in long-term therapy for inborn errors of
      vitamin B(12) absorption?
AB  - Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary
      intrinsic factor deficiency (HIFD) and Imerslund-Grasbeck disease (IGD). HIFD is
      secondary to mutations in the HIF gene while IGD is due to mutations in one of
      the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or
      amnionless (AMN). These disorders lead to intracellular Cbl depletion which in
      turn causes megaloblastic bone marrow failure, accumulation of homocysteine and
      methylmalonic acid (MMA), and methionine depletion. The clinical presentation
      reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and
      megaloblastic anemia. Mixed proteinuria, when it is present is strongly
      suggestive of IGD. Accurate diagnosis is always an emergency because early
      detection and treatment with life-long parenteral pharmacological doses of
      hydroxocobalamin are life saving and prevent further deterioration. However, the
      optimal frequency for cobalamin injections as a maintenance therapy is poorly
      reported. In order to evaluate the optimal maintenance schedule of cobalamin
      injections, we retrospectively collected clinical, biological, molecular and
      treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike
      previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin
      twice a year was enough to ensure a normal clinical status and keep the
      hematological and metabolic parameters in the normal range. These data suggest
      that patients affected with inborn errors of cobalamin absorption may be safely
      long-term treated with cobalamin injections every 6 months with careful follow-up
      of hematological and metabolic parameters. This maintenance regime is beneficial
      because the patients' quality of life improves.

PMID- 22854513
TI  - Nutritional treatment for inborn errors of metabolism: indications, regulations,
      and availability of medical foods and dietary supplements using phenylketonuria
      as an example.
AB  - Medical foods and dietary supplements are used to treat rare inborn errors of
      metabolism (IEM) identified through state-based universal newborn screening.
      These products are regulated under Food and Drug Administration (FDA) food and
      dietary supplement statutes. The lack of harmony in terminology used to refer to
      medical foods and dietary supplements and the misuse of words that imply that FDA
      regulates these products as drugs have led to confusion. These products are
      expensive and, although they are used for medical treatment of IEM, third-party
      payer coverage of these products is inconsistent across the United States.
      Clinicians and families report termination of coverage in late adolescence,
      failure to cover treatment during pregnancy, coverage for select conditions only,
      or no coverage. We describe the indications for specific nutritional treatment
      products for IEM and their regulation, availability, and categorization. We
      conclude with a discussion of the problems that have contributed to the paradox
      of identifying individuals with IEM through newborn screening but not
      guaranteeing that they receive optimal treatment. Throughout the paper, we use
      the nutritional treatment of phenylketonuria as an example of IEM treatment.

PMID- 22854517
TI  - Association between lung function in school children and exposure to three
      transition metals from an e-waste recycling area.
AB  - The informal processing of electronic waste or e-waste contributes to the release
      of high concentrations of transition metals into the ambient air. The damage
      caused by chromium, nickel and manganese exposure on lung function in school
      children from an e-waste recycling area and the role of oxidative stress in this
      process were evaluated. We recruited school children (n=144, 8-13 years) from an
      e-waste recycling area in China compared with the control. Spirometry was
      performed to assess lung function status. The blood levels of chromium, nickel
      and manganese, antioxidant enzyme activities and lipid peroxidation of the
      subjects were examined. The concentrations of blood manganese (bMn) and serum
      nickel (sNi) in the exposed group were significantly higher than those in
      controls for all three age groups. The forced vital capacity value of boys aged 8
      9 years was significantly lower than that of the control. Malondialdehyde levels
      and superoxide dismutase activities increased significantly in children aged 8-9
      years from e-waste environment, but catalase activities declined. School children
      from an e-waste recycling area were exposed to high levels of the three
      transition metals. The accumulation of bMn and sNi may be risk factors for
      oxidative damage and decreased pulmonary function.

PMID- 22854518
TI  - Lifetime organophosphorous insecticide use among private pesticide applicators in
      the Agricultural Health Study.
AB  - Organophosphorous insecticides (OPs) are the most commonly used insecticides in
      US agriculture, but little information is available regarding specific OP use by
      individual farmers. We describe OP use for licensed private pesticide applicators
      from Iowa and North Carolina in the Agricultural Health Study (AHS) using
      lifetime pesticide use data from 701 randomly selected male participants
      collected at three time periods. Of 27 OPs studied, 20 were used by >1%. Overall,
      95% had ever applied at least one OP. The median number of different OPs used was
      4 (maximum=13). Malathion was the most commonly used OP (74%) followed by
      chlorpyrifos (54%). OP use declined over time. At the first interview (1993
      1997), 68% of participants had applied OPs in the past year; by the last
      interview (2005-2007), only 42% had. Similarly, median annual application days of
      OPs declined from 13.5 to 6 days. Although OP use was common, the specific OPs
      used varied by state, time period, and individual. Much of the variability in OP
      use was associated with the choice of OP, rather than the frequency or duration
      of application. Information on farmers' OP use enhances our ability to
      characterize and understand the potential health effects of multiple OP
      exposures.

PMID- 22854519
TI  - Length-dependent effect of single-walled carbon nanotube exposure in a dynamic
      cell growth environment of human alveolar epithelial cells.
AB  - Despite the great use of nanomaterials for engineering and medical applications,
      nanomaterials may have adverse consequences by accidental exposure, because of
      their nanoscale size, composition and shape. Like many nanomaterials, carbon
      nanotubes (CNTs) have been used for many proven applications, but the size of the
      CNTs makes them more readily become airborne and can therefore create the risk of
      being inhaled by a worker. In this study, we evaluated single-walled CNT (SWCNT)
      induced effects on cellular responses such as cell proliferation, inflammatory
      response and oxidative stress in dynamic cell growth condition. A dynamic cell
      growth environment was established to mimic the dynamic changes in the amount of
      circumferential and longitudinal expansion and contraction occurred during normal
      breathing movement in the lung. Two different length (short: outer diameter (OD)
      1-2 nm, length 0.5-2 MUm; long: OD 1-2 nm, length 5-30 MUm) of SWCNTs were used
      at different exposure concentrations (5, 10 and 20 MUg/ml) during the different
      exposure duration (24, 48 and 72 h). Dynamic environment facilitated altered
      interaction between SWCNTs and A549 monolayer. Cellular responses in dynamic
      condition were significantly different from those in static condition. Moreover,
      cellular responses were dependent on the length of SWCNTs both in static and
      dynamic cell growth conditions.

PMID- 22854520
TI  - EVAR reintervention management strategies in contemporary practice.
AB  - It is known that following an endovascular aneurysm repair (EVAR) procedure,
      patients may experience endoleaks, device migration, stent fractures, graft
      deterioration, or aneurysm growth that might require a reintervention. In this
      review management strategies of reinterventions after EVAR in contemporary
      practice will be discussed. The current endovascular treatment options of Type I
      endoleak involve securing of the attachment site with percutaneous transluminal
      balloon angioplasty, stent-graft extension, or placement of a stent at the
      proximal attachment site. Moreover, the use of endostaples to secure the position
      of the proximal cuff to the primary endograft have been developed. Type II
      endoleaks can be managed conservatively if the aneurysm is shrinking or remains
      stable. Otherwise, reinterventions include transarterial embolization,
      translumbar embolization, transcaval embolization, direct thrombin injection, and
      endoscopic or open ligation of the lumbar and mesenteric arteries. There is
      little debate regarding the treatment of type III endoleaks, including
      deployement of additional stent graft components to bridge the defect.
      Endovascular treatment of endotension includes endovascular conversion stent or
      relining of the stent graft. Alternative options are puncture of the aneurysm sac
      and removal of the aneurysm sac content. In case of migration large balloon
      expandable stents can be used to improve the seal between the components, or
      devices that deploy staples to secure endovascular grafts to the aortic wall to
      secure endovascular components together. In conclusion, the first treatment
      options for reinterventions after EVAR are catheter based nowadays.

PMID- 22854521
TI  - The use of endoanchors in repair EVAR cases to improve proximal endograft
      fixation.
AB  - AIM: The aim of this paper was to evaluate short-term outcome of the use of
      endoanchors to secure the primary migrated endograft and additional extender
      cuffs to the aortic wall in patients with previous failed endovascular aortic
      aneurysm repair. METHODS: Consecutive patients who needed proximal repair of a
      primary failed endograft due to migration (with or without type IA endoleaks)
      were treated with endoanchors, with or without additional extender cuffs. Data of
      this group were prospectively gathered in vascular referral centers that were
      early adopters of the endoanchor technique. Preprocedural and periprocedural data
      were prospectively gathered and retrospectively analyzed. Follow-up after
      endoanchor placement consisted of regular hospital visits, with computed
      tomography or duplex scanning at 1, 6, and 12 months. RESULTS: From July 2010 to
      May 2011, 11 patients (8 men), mean age 77 years (range, 59-88 years), were
      treated with endoanchors for a failed primary endograft (2 Excluder endografts, 1
      AneuRx endograft, and 8 Talent endografts) due to distal migration of the main
      body, with or without type IA endoleak. Revision consisted of using endoanchors
      to secure the body of the primary endograft to the aortic wall to avoid
      persistent migration. Most patients had additional proximal extender cuffs with
      suprarenal fixation, which were secured with endoanchors to the aortic wall and
      in some patients also to the primary endograft. A median of 6 endoanchors were
      implanted. All endoanchors were positioned correctly but one. One endoanchor
      dislodged but was successfully retrieved using an endovascular snare. During a
      mean follow-up of 10 months (range, 3-18 months) no endoanchor-related
      complications or renewed migration of the endografts occurred. Two patients
      underwent repeat intervention due to persistent type IA endoleak during follow
      up. CONCLUSION: The use of endoanchors to secure migrated endografts to the
      aortic wall is safe and feasible and might help to overcome persistent migration
      of primary failed endografts. In combination with the use of sole extender cuffs
      the majority of proximal EVAR failures can be solved.

PMID- 22854522
TI  - Current knowledge on EVAR with the ultra-low profile Ovation Abdominal Stent
      graft System.
AB  - Endovascular aneurysm repair (EVAR) has revolutionized the treatment of
      infrarenal abdominal aortic aneurysms (AAAs). The continuous collaboration of
      surgeons and bioengineers in the improvement of the devices the last two decades,
      lead to a continuous redesigning and improvement of the various endografts. In
      the last few years, the majority of companies have developed renewed models of
      grafts and have modified delivery systems tending to lower profile in order to
      deal with difficult anatomies. The ultra low profile 14F OD Ovation (Trivascular)
      Abdominal Stent-graft System with innovative sealing technology achieved through
      inflatable sealing rings, allows treatment of AAAs with small in diameter access
      vessels that might be unsuitable for EVAR with other currently available stent
      grafts. The aim of the present paper was to analyze the technical characteristics
      and properties of this endograft and to review the current literature.

PMID- 22854523
TI  - Evidence for endovascular aneurysm repair in patients with highly angulated neck
      anatomy.
AB  - Patients with highly angulated neck anatomy may account for up to a fifth of all
      patients treated by endovascular repair. However there is evidence that these
      patients have worse early and long-term outcomes, including sac expansion. This
      review explores the evidence supporting the use of endovascular repair in the
      setting of severe neck angulation, with particular emphasis on new technology
      with devices that have expanded the anatomical criteria for endovascular aneurysm
      repair such as the Lombard Aorfix and Medtronic Endurant endografts.

PMID- 22854524
TI  - The role of superficial femoral artery endoluminal bypass in long de novo lesions
      and in-stent restenosis.
AB  - AIM: Results of endovascular treatment for long de novo lesions of the
      superficial femoral artery (SFA) are limited by in-stent restenosis (ISR).
      Polytetrafluoroethylene (PTFE) covered stents are developed to reduce the
      incidence of ISR. This study was conducted to summarize available data on the use
      of endoprosthesis in the treatment of SFA occlusive disease and to evaluate their
      use in the treatment of ISR. METHODS: A systematic literature search was
      performed, using MEDLINE, EMBASE and Cochrane databases. Reports on the
      application of Hemobahn(r) and Viabahn(r) endoprosthesis in the treatment of long
      de-novo lesions and ISR of the SFA were included. RESULTS: A total of 19 articles
      were included. Technical success rates varied between 95-100%. Case series have
      shown 1-year primary patency rates varying between 44% and 86%, with secondary
      patency rates between 58% and 93%. Large differences in patient and lesion
      characteristics, medical therapy and developments in stent-graft design
      complicate comparisons between studies. Randomized studies have shown a
      superiority of the endoprosthesis above angioplasty only and similar patency
      rates with above-knee prosthetic femoro-popliteal bypass up to 48 months. Data on
      the use of endografts for ISR are scarce. CONCLUSION: The use of an
      endoprosthesis for SFA occlusive disease is an effective and safe treatment
      strategy for long de novo lesions. Patient selection and adequate medical support
      appear to be important in achieving long term patency. Data focusing on the
      effectiveness of endoprosthesis for ISR are still limited.

PMID- 22854525
TI  - Standard balloon angioplasty versus angioplasty with paclitaxel-eluting balloons
      for femoropopliteal artery stenosis.
AB  - AIM: The aim of this article was to review the available literature on the use of
      drug-coated balloons (DCB) for endovascular treatment of femoropopliteal arterial
      stenosis. METHODS: Manual searches of articles, presentations, and clinical
      trials were performed. Selected references were reviewed and summarized. RESULTS:
      Due to the high morbidity associated with femoropopliteal bypass, endovascular
      approaches, such as balloon angioplasty and stent placement, have become the
      first line of therapy for isolated, de novo femoral atherosclerosis. However,
      percutaneous interventions have been limited by restenosis. In an effort to
      overcome this obstacle, the use of antiproproliferative drugs to inhibit
      hyperplasia has been attempted. The success of drug-eluting stents (DES) in the
      coronary circulation has not been reproduced in the femoropopliteal segment.
      Animal and human experiments have shown prolonged inhibition of intimal
      hyperplasia with single delivery of large doses of paclitaxel during balloon
      angioplasty. Recent randomized trials have shown significant advantages at 12 and
      24 month angiographic follow-up with the use of DCB when compared to standard
      balloon angioplasty. CONCLUSION: Several clinical trials have demonstrated
      promising early results with the use of DCB in treating femoropopliteal stenosis.
      However, long term results, exact indications, and optimal applications are yet
      to be determined.

PMID- 22854526
TI  - Refining stent technologies for femoral interventions.
AB  - Stents were created as a mechanical scaffold to prevent vessel recoil and luminal
      renarrowing after percutaneous transluminal angioplasty (PTA). In femoropopliteal
      arteries, indication for stent implantation remains a topic much debated on,
      especially in long lesion configurations. Ever since the first stents were
      introduced on the market, in-stent restenosis (ISR) has been an important issue.
      The evolution in stent design has known a major progression in the last decades
      from the first generation of stents, plagued with high fracture rates and low
      primary patency rates, to the design of newer stents to tackle these outcomes.
      More flexible and longer stents decreased the high fracture rates and drug
      eluting stents offered a solution to the restenosis rates by local drug
      application. The difficult recrossibility of the lesion because of the presence
      of a permanent vascular scaffold is an obstacle that the drug-coated balloon
      (DCB) overcomes. Future perspectives in the treatment of femoropopliteal lesions
      are found in the bioresorbable stent implantation. The bioresorbable stent
      combines the advantages of a drug-eluting scaffolding stent without the remainder
      of a foreign object in the long-term. Further investigations in this area will
      eventually evolve in the creation of a superior endovascular treatment modality
      with high long-term patency rates and minimal detriments.

PMID- 22854527
TI  - Treatment for long-segment femoro-popliteal obstructions: initial experience with
      a 4-F compatible self-expanding nitinol stent and review of the literature.
AB  - AIM: The aim of this paper was to evaluate the efficacy of a novel 4-F compatible
      self-expanding Nitinol stent for the treatment of long femoro-popliteal
      obstructions. METHODS: This retrospective analysis includes patients with femoro
      popliteal obstructions >= 120 mm in length, treated with a novel Nitinol stent
      (Pulsar-18) between February 2010 and December 2011. Patients were categorized as
      either intermittent claudication (IC) or critical limb ischemia (CLI). Primary
      endpoint was primary patency, secondary endpoints were target lesion
      revascularization (TLR). RESULTS: A total of 31 patients (IC: N=18 and CLI: N=13)
      were included in the present series. Mean age was 73.3 +/- 10.1 years and 71%
      (22/31) of the patients were male. Primary intervention was performed in 77.4%
      (24/31) of the patients and re-do revascularization in the remaining. Mean lesion
      length of femoro-popliteal obstructions was 163.5 +/- 32.5 mm. Technical success
      was obtained in all patients. Mean follow-up duration was 316 +/- 198 days.
      Primary patency rates were 83.3% in IC and 80.0% in CLI patients at 6 months and
      64.1% and 54.9% at 12 months, respectively (P=0.84). Target lesion
      revascularization occurred in 5.6% of IC and 20.0% of CLI patients at 6 months
      and in 14.1% and 36.0% at 12 months, respectively (P=0.43). CONCLUSION:
      Endovascular stenting of long femoro-popliteal lesions using the Pulsar-18 stent
      provides acceptable results with patency and restenosis rates comparable with
      data from literature for stenting of long femoro-popliteal obstructions.

PMID- 22854528
TI  - Innovative technologies for SFA occlusions: drug coated balloons in SFA lesions.
AB  - The concept of using a balloon catheter to directly deliver an antiproliferative
      drug at the site of injury has become one of the most interesting technological
      developments in endovascular therapy. There have been important advances in
      knowledge concerning balloon-based drug delivery technologies during the last
      years, and different methods have been developed by different companies to coat
      the balloon with the antiproliferative agent. Currently there is a rapidly
      increasing clinical study program using drug coated balloons (DCB) in different
      locations and indications. There are four already finished randomized studies in
      patients with superficial femoral artery lesions investigating the efficacy of
      paclitaxel release by DCB, and all demonstrated significantly improved patency
      rates compared to balloon angioplasty with non coated balloons. DCB offer several
      advantages compared to drug eluting stents, since any stentless technology for
      improvement of longterm patency is preferable to overcome the drawbacks of
      stenting. This technology has demonstrated the capacity to have a significant
      impact on the practice of percutaneous cardiovascular interventions in the
      future.

PMID- 22854530
TI  - Medical treatment of small abdominal aortic aneurysm.
AB  - Conventional open repair or endovascular aneurysm repair is indicated for
      infrarenal abdominal aortic aneurysm (AAA) when the diameter of the latter is >=
      5.5 cm. This therapeutic strategy is based on results of randomized trials of
      open repair versus ultrasound surveillance of small AAA (<5.5 cm). Studies of
      screening for AAA have shown that >90% of aneurysms detected are small aneurysms
      (<5.5 cm). Despite the low annual risk of rupture of these aneurysms, patients
      with small AAA are left with a potentially life-threatening disease for which no
      immediate treatment is available. Hence, medical treatment directed at limiting
      the expansion of small AAA has emerged as an alternative therapeutic strategy.
      Randomized trials of doxycycline, roxithromycin, and propranolol in patients with
      small AAA have been published. The results of the doxycycline and roxithromycin
      trials suggest that both medications can limit AAA expansion, especially during
      the first year of treatment. Propranolol did not limit AAA expansion, and the
      trials were stopped because of its serious side effects. In other studies,
      statins and indomethacin have also been shown to limit AAA expansion. However,
      these studies were observational with relatively small numbers of patients. Thus,
      large randomized controlled trials with long follow-up are needed to objectively
      assess the efficacy of medications that have shown potential in limiting AAA
      expansion. In addition, recent evidence of regression of AAA in experimental
      animal models is likely to change our concepts of the molecular pathogenesis of
      AAA, and could make medical treatment of small AAA a possibility.

PMID- 22854529
TI  - Latest recanalization techniques for complex superficial femoral artery
      occlusions.
AB  - Complex, long segment lesions of the superficial femoral artery (SFA) are common,
      occurring in 40% of patients with peripheral vascular disease. In particular,
      chronic total occlusions (CTOs) continue to pose a challenge in the endovascular
      management of SFA disease. Several conventional wire and catheter based
      techniques have been described including subintimal recanalization and retrograde
      techniques. In addition, advances in endovascular technology have led to the
      development of a series of new devices aimed specifically at facilitating the
      crossing of long segment SFA occlusions or establishing re-entry of the true
      lumen. Here we present an overview of the minimally invasive techniques used to
      recanalize CTOs of the SFA and the latest specialized devices available for both
      recanalization and re-entry, as well as a summary of the literature supporting
      their application.

PMID- 22854531
TI  - Flow characteristics of LIMA radial composite sequential bypass grafting and
      single LIMA and saphenous vein sequential bypass grafting performed under OPCAB.
AB  - AIM: The present study was aimed to compare the hemodynamic flow characteristics
      of LIMA radial artery composite sequential bypass grafting and with single LIMA
      and saphenous vein sequential bypass grafting performed by off-pump coronary
      artery bypass grafting (OPCAB). METHODS: Between March 2007 and February 2008,
      121 OPCAB patients were prospectively divided into two groups; Group I (N.=70,
      left internal thoracic artery [LITA]-left anterior descending [LAD] and Ao-SV
      sequential grafting), and Group II (N.=51, LITA-RA sequential grafting). The mean
      flow, pulsatility index (PI) and back flow (BF) were measured using the Transit
      time flow meter (TTFM). In Group II, the proximal (p-LITA) and distal LITA (d
      LITA) flow in relation to the RA side branch anastomosis were measured
      separately. RESULTS: The mean flow and PI of the proximal SV sequential graft and
      that of the RA graft were 64.4 +/- 37.3 mL/min and 2.6 +/- 1.6 versus 27.3 +/-
      18.6 mL/min and 4.1 +/- 4.4, respectively (P<0.05). In Group I, the mean LITA
      flow, PI, and BF were 26.9 +/- 16.4 mL/min, 2.6 +/- 1.5, and 3.1 +/- 6.1% whereas
      in Group II those of the p-LITA were 37.3 +/- 21.6 mL/min, 2.3 +/- 1.0, and 2.0
      +/- 3.5% and the d-LITA were 18.8 +/- 12.2 mL/min, 3.9 +/- 3.3 and 7.4 +/- 11.8%
      (P<0.01). CONCLUSION: The results of the present data suggest the hemodynamic
      flow characteristics of composite bypass grafting to be inferior to the single
      LIMA and separate aorta-saphenous vein bypass grafting strategy. However, a
      longer follow up is warranted to assess the implications of these findings on
      graft durability.

PMID- 22854532
TI  - Spherical dilatation of the apex in failing left ventricles: a target for
      surgical remodelling techniques.
AB  - AIM: The present study investigates the geometry of failing left ventricles with
      a special focus on apical deformation. A new surgical remodelling technique is
      evaluated. METHODS: In 124 patients with impaired left ventricular function
      (EF<40%) undergoing coronary artery bypass grafting (CABG) left ventricular (LV)
      geometry was evaluated by MRI scanning before and after surgery. Besides the
      sphericity index (SI) two further indices were calculated, longitudinal EF (LEF)
      and an apical conicity index (ACI). The results were compared to 15 patients with
      coronary heart disease and normal LV function and 10 test persons. In 35 patients
      with impaired LV function perpendicular apical compression (AC) stitches were
      placed. RESULTS: In failing left ventricles indexed LV length increased (5.3 +/-
      0.6 cm/m2 vs. 4.7 +/- 0.8 cm/m2 in control patients and 4.6 +/- 0.3 cm/m2 in test
      persons, P=0.03). LEF was reduced (6% +/- 4 versus 22% +/- 6 and 19% +/- 7
      P=0.04). The classical SI was 0.56 +/- 0.06 in heart failure patients, 0.50 +/-
      0.05 in control patients and 0.48 +/- 0.04 in test persons. The ACI were 0.75 +/-
      0.06, 0.58 +/- 0.06 and 0.57 +/- 0.04 respectively (P<0.05), indicating a
      pronounced dilatation at the apex. After apical compression LEF improved to 15 +/
      1%, the ACI to 0.64 +/- 0.04 (P=0.04). LVEDV (166 +/- 11 mL [AC] vs. 196 +/- 14
      mL [without AC]) as well as LV-EF (48 +/- 3% [AC] vs. 36 +/- 2% [without AC])
      significantly improved only after remodelling (P<0.05). CONCLUSION: Apical
      compression improved ventricular geometry and ventricular function in patients
      with dialatation of the left ventricular apex.

PMID- 22854533
TI  - Lycopalhine A, a novel sterically congested Lycopodium alkaloid with an
      unprecedented skeleton from Palhinhaea cernua.
AB  - A novel sterically congested Lycopodium alkaloid named lycopalhine A (1) that
      possesses a fused hexacyclic (5/5/5/6/6/6) ring system comprising a 5,9-diaza
      tricyclo[6.2.1.0(4,9)]undecane moiety and a tricyclo[5.2.1.0(4,8)]decane moiety
      was isolated from Palhinhaea cernua L. The structure and absolute configuration
      were determined by spectroscopic and computational methods.

PMID- 22854534
TI  - Prediction of 3-hydroxypyridin-4-one (HPO) log K1 values for Fe(III).
AB  - As a means to aid in the design of 3-hydroxypyridin-4-ones (HPOs) intended for
      use as therapeutic Fe(3+) chelating agents, a novel methodology has been
      developed using quantum mechanical (QM) calculations for predicting the iron
      binding affinities of the compounds (more specifically, their log K(1) values).
      The reported/measured HPO log K(1) values were verified through their correlation
      with the corresponding sum of the compounds' ligating group pK(a) values. Using a
      training set of eleven HPOs with known log K(1) values, reliable predictions are
      shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model
      chemistry (with Bondi radii, and water as solvent). With this methodology, the
      observed log K(1) values for the training set compounds are closely matched by
      the predicted values, with the correlation between the observed and predicted
      values giving r(2) = 0.9. Predictions subsequently made by this method for a test
      set of 42 HPOs of known log K(1) values gave predicted values accurate to within
      +/-0.32 log units. In order to further investigate the predictive power of the
      method, four novel HPOs were synthesised and their log K(1) values were
      determined experimentally. Comparison of these predicted log K(1) values against
      the measured values gave absolute deviations of 0.22 (13.87 vs. 14.09), 0.02
      (14.31 vs. 14.29), 0.12 (14.62 vs. 14.50), and 0.13 (15.04 vs. 15.17). The
      prediction methodology reported here is the first to be provided for predicting
      the absolute log K(1) values of iron-chelating agents in the absence of pK(a)
      values.

PMID- 22854535
TI  - Adenosine induces apoptosis in SBC-3 human lung cancer cells through A(3)
      adenosine receptor-dependent AMID upregulation.
AB  - BACKGROUND/AIMS: We have shown that A(3) adenosine receptor mediates apoptosis in
      human lung cancer cells such as A549 cells, an epithelial adenocarcinoma cell
      line, and Lu-65 cells, a giant cell cancer cell line, via each different
      signaling pathway. AMID, a pro-apoptotic protein, induces caspase-independent
      apoptosis by accumulating in the nucleus. The present study investigated AMID
      dependent apoptosis through A(3) adenosine receptor in SBC-3 cells, a human small
      cell lung cancer cell line. METHODS: MTT assay, TUNEL staining, flow cytometry
      using propidium iodide and annexin V-FITC, and Western blotting were carried out
      in SBC-3 cells transfected with and without the siRNA to silence the A(3)
      adenosine receptor-targeted gene or the AMID-targeted gene. RESULTS: Adenosine
      induced SBC-3 cell apoptosis in a concentration (0.01-10 mM) and treatment time
      (24-72 h)-dependent manner, and a similar effect was obtained with the A(3)
      adenosine receptor agonist 2-Cl-IB-MECA. Adenosine-induced SBC-3 cell death was
      inhibited by the A(3) adenosine receptor inhibitor MRS1191, knocking-down A(3)
      adenosine receptor, or knocking-down AMID. Adenosine upregulated expression of
      the AMID mRNA and protein in SBC-3 cells, that is suppressed by knocking-down
      A(3) adenosine receptor. In addition, adenosine increased nuclear AMID
      localization in concert with decreased cytosolic AMID localization. CONCLUSION:
      The results of the present study show that adenosine induces SBC-3 cell apoptosis
      by upregulating AMID expression and promoting AMID translocation into the nucleus
      via A(3) adenosine receptor.

PMID- 22854536
TI  - Smoking behaviour, knowledge, attitudes and practice among healthcare providers
      in Kahramanmaras, Turkey.

PMID- 22854537
TI  - Change in body fat during a family-based treatment of obesity in children: the
      relative importance of energy intake and physical activity.
AB  - OBJECTIVE: The aim of the current study was to examine to what extent changes in
      reported energy intake and physical activity predict changes in body fat during a
      family-based outpatient treatment of obesity in children. METHODS: Total body fat
      (DXA), reported energy intake (4-day diet record), and physical activity
      (accelerometer) was measured in 99 children (age 7-12 years, mean BMI SDS = 2.99)
      at baseline as well as after 6 months 2 years of treatment. Repeated measures
      (GLM), growth modeling, and structural equation modeling (SEM) were applied in
      the data analyses. RESULTS: There was significant decrease in body fat, reported
      energy intake, and physical activity at both follow-ups (p < 0.001) compared to
      baseline. Changes in reported energy intake from baseline to 6 months predicted a
      decrease in body fat from baseline to 6 months (beta = 0.68, p < 0.001). In
      addition, changes in reported energy intake had a strong indirect effect on body
      fat at 2-year follow-up, mediated by changes in body fat from baseline to 6
      months (indirect beta = 0.50, p < 0.001). Changes in physical activity did not
      predict changes in body fat during treatment. CONCLUSIONS: Changes in reported
      energy intake significantly affected body fat at 6 months and indirectly
      predicted the amount of body fat at 2-year follow-up. The indirect effect was
      mediated by a decrease in body fat obtained during the first phase of treatment.

PMID- 22854538
TI  - Spatio-temporal patterns of Cu contamination in mosses using geostatistical
      estimation.
AB  - Several recent studies have reported temporal trends in metal contamination in
      mosses, but such assessments did not evaluate uncertainty in temporal changes,
      therefore providing weak statistical support for time comparisons. Furthermore,
      levels of contaminants in the environment change in both space and time,
      requiring space-time modelling methods for map estimation. We propose an
      indicator of spatial and temporal variation based on space-time estimation by
      indicator kriging, where uncertainty at each location is estimated from the local
      distribution function, thereby calculating variability intervals for comparison
      between several biomonitoring dates. This approach was exemplified using copper
      concentrations in mosses from four Portuguese surveys (1992, 1997, 2002 and
      2006). Using this approach, we identified a general decrease in copper
      contamination, but spatial patterns were not uniform, and from the uncertainty
      intervals, changes could not be considered significant in the majority of the
      study area.

PMID- 22854539
TI  - Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients.
AB  - The objective of our present study was to develop a warfarin dosing algorithm for
      the Omani patients, as performances of warfarin dosing algorithms vary across
      populations with impact on the daily maintenance dose. We studied the functional
      polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the
      warfarin maintenance dose in an admixed Omani patient cohort with Caucasian,
      African and Asian ancestries. We observed a 64-fold inter-patient variability for
      warfarin to achieve stable international normalized ratio in these patients.
      Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep
      vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1
      loci were significantly associated with warfarin dose in the studied patient
      population. However, multiple regression model showed that only the atrial
      fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and
      VKORC1 GA and AA genotypes remained significant. A multivariate model, which
      included demographic, clinical and pharmacogenetic variables together explained
      63% of the overall inter-patient variability in warfarin dose requirement in this
      microgeographically defined, ethnically admixed Omani patient cohort on warfarin.
      This locally developed model performed much better than the International
      Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only
      explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G>A
      polymorphism emerged as the single most important predictor of warfarin dose
      variability, even in this admixed population (partial R(2)=0.45).

PMID- 22854540
TI  - Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin
      reflectance and freckles in Japanese.
AB  - Most studies on the genetic basis of human skin pigmentation have focused on
      people of European ancestry and only a few studies have focused on Asian
      populations. We investigated the association of skin reflectance and freckling
      with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA
      samples were obtained from a total of 653 Japanese individuals (ages 19-40 years)
      residing in Okinawa; skin reflectance was measured using a spectrophotometer and
      freckling status was determined for each individual. Lightness index (L*) and
      freckling status were not correlated with age, body mass index or ancestry
      (Ryukyuan or Main Islanders of Japan). Among the 10 nonsynonymous variants that
      were identified by direct sequencing of the coding region of MC1R, two variants-
      R163Q and V92M--with the derived allele frequencies of 78.6 and 5.5%,
      respectively, were most common. Multiple regression analysis showed that the 163Q
      allele and the presence of nonsynonymous rare variants (allele frequencies <5%)
      were significantly associated with an increase in sex-standardized skin lightness
      (L* of CIELAB (CIE 1976 (L*a*b*) color space)) of the inner upper arm. Relative
      to the 92V allele, the 92M allele was significantly associated with increased
      odds of freckling. This is the first study to show an association between the
      163Q allele and skin reflectance values; this association indicated that light
      toned skin may have been subjected to positive selection in East Asian people.

PMID- 22854541
TI  - Paternal uniparental isodisomy of chromosome 22 in a patient with metachromatic
      leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage
      disease caused by deficiency of the enzyme arylsulfatase A encoded by the ARSA
      gene located on 22q13.33. Typically, in autosomal recessive disease, a patient
      inherits two mutations from both parents who are heterozygous carriers. However,
      in some instances, it is possible to develop the disease by uniparental isodisomy
      (UPiD), in which two copies of the same mutated allele are inherited from only
      one carrier parent. Here, we report the first patient with MLD caused by UPiD of
      chromosome 22. The patient has a homozygous missense mutation, P136T, on ARSA.
      Family study of the ARSA gene and leukocyte enzyme activity revealed that his
      father and sister were heterozygous carriers, but his mother possessed only wild
      type alleles and normal enzyme activity. Karyotypes of the patient and the
      parents were normal. Microsatellite analysis showed no discrepancy of parentage,
      and paternal UPiD of chromosome 22 was indicated. Finally, genome-wide single
      nucleotide polymorphism array confirmed the region of UPiD was extended to the
      entire chromosome 22 of the patient.

PMID- 22854542
TI  - Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways
      based on microRNA expression signature in prostate cancer.
AB  - microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and
      metastasis. miRNAs are aberrantly expressed in many human cancers and can
      function as tumor suppressors or oncogenes that target many cancer-related genes.
      This study seeks to identify novel miRNA-regulated molecular pathways in prostate
      cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed
      that 56 miRNAs were significantly downregulated in PCa compared with non-PCa
      tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR
      222 and miR-31) to investigate their functional significance in PCa cells.
      Expression levels of these four miRNAs were validated in PCa specimens (15 PCa
      tissues and 17 non-PCa tissues) to confirm that they were significantly reduced
      in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR
      31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3
      and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in
      PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants
      to identify the pathways they affect showed that many cancer-related genes are
      regulated by these miRNAs in PC3 cells. Identification and categorization of the
      molecular pathways regulated by tumor suppressive miRNAs could provide new
      information about the molecular mechanisms of PCa tumorigenesis.

PMID- 22854543
TI  - [Structural equation modeling on successful aging in elders - focused on
      selection . optimization . compensation strategy -].
AB  - PURPOSE: This study was designed to construct and test a structural equation
      modeling on specific domain health status and the Selection . Optimization .
      Compensation (SOC) strategy affecting successful aging in elderly people.
      METHODS: The model construction was based on the SOC model by Baltes and Baltes.
      Interviews were done with 201 elderly people aged 65 or older. Interview contents
      included demographics, functional health status, emotional health status, social
      health status, SOC strategies, and successful aging. Data were analyzed using
      SPSS 15.0 and AMOS 7.0. RESULTS: Model fit indices for the modified model were
      GFI=.93, CFI=.94, and RMSEA=.07. Three out of 7 paths were found to have a
      significant effect on successful aging in this final model. Functional health
      status had a direct and positive effect on successful aging. Emotional health
      status influenced successful aging through SOC strategies. CONCLUSION: This study
      suggests that interventions for improving functional health status and for
      strengthening SOC strategies are critical for successful aging. Continuous
      development of a variety of successful aging programs using SOC strategy is
      suggested.

PMID- 22854544
TI  - [Development and evaluation of a small group-based cardiocerebrovascular disease
      prevention education program for male bus drivers].
AB  - PURPOSE: This study was conducted to examine effects of a small group-based
      cardiocerebrovascular disease (CVD) prevention education program on knowledge,
      stage of change and health behavior among male bus drivers with CVD risk factors.
      METHODS: A non-equivalent control group pretest-posttest design was used.
      Participants were 68 male bus drivers recruited from two urban bus companies.
      Participants from the two groups were selected by matching age, education and
      risk factors. Experimental group (n=34) received a small group-based CVD
      prevention education program 8 times over 6 weeks and 3 times through telephone
      interviews at 2-week intervals. Data were collected between December, 2010 and
      March, 2011, and were analyzed using chi-square test, t-test, and repeated
      measure analysis of variance with SPSS/Win18.0. RESULTS: Experimental group
      showed significantly higher scores in CVD prevention knowledge (p<.001) and
      health behavior (p<.001) at 6 and 12 weeks after intervention. Participants in
      pre-contemplation and contemplation stages made progress to contemplation and
      action. This was significantly better at 6 and 12 weeks after intervention
      (p<.001). CONCLUSION: Results suggest that small group-based education programs
      for CVD prevention are effective in increasing knowledge, stage of change, and
      health behavior to prevent CVD among male bus drivers with CVD risk.

PMID- 22854545
TI  - [The effects of pre-operative visual information and parental presence
      intervention on anxiety, delirium, and pain of post-operative pediatric patients
      in PACU].
AB  - PURPOSE: The purpose of this study was to test whether pre-operative visual
      information and parental presence had positive effects on anxiety, delirium, and
      pain in pediatric patients who awoke from general anesthesia in a post-surgical
      stage. METHODS: This study used a non equivalent control-group post test design
      (n=76). Independent variables were provision of pre-operative visual information
      and parental presence for post-surgical pediatric patients in PACU (post
      anesthesia care unit). Dependent variables were anxiety, delirium, and pain in
      the pediatric patients measured three times at 10 minute intervals after
      extubation in the PACU. Measurements included Numerical Rating Scale for
      assessing state anxiety, Pediatric Anesthesia Emergence Delirium Scale by Sikich
      & Lerman (2004) for delirium, and Objective Pain Scale by Broadman, Rice &
      Hannallah (1988) for pain. RESULTS: Experimental group showed significantly
      decreased state anxiety at time points-10, 20, and 30 minutes after extubation.
      Delirium was significantly lower at 10 minutes and 30 minutes after extubation in
      the experimental group. Pain was significantly lower at 10 minutes after
      extubation in the experimental group. CONCLUSION: The results of this study
      suggest that this intervention can be a safe pre-operative nursing intervention
      for post-surgical pediatric patients at PACU.

PMID- 22854546
TI  - [Subjectivity of nursing college students' awareness of gender equality: an
      application of Q-methodology].
AB  - PURPOSE: This study was done to identify the awareness of gender equality among
      nursing college students, and to provide basic data for educational solutions and
      desirable directions. METHODS: A Q-methodology which provides a method of
      analyzing the subjectivity of each item was used. 34 selected Q-statements from
      each of 20 women nursing college students were classified into a shape of normal
      distribution using 9-point scale. Subjectivity on the equality among genders was
      analyzed by the pc-QUANL program. RESULTS: Four types of awareness of gender
      equality in nursing college students were identified. The name for type I was
      'pursuit of androgyny', for type II, 'difference-recognition', for type III,
      'human-relationship emphasis', and for type IV, 'social-system emphasis'.
      CONCLUSION: The results of this study indicate that different approaches to
      educational programs on gender equality are recommended for nursing college
      students based on the four types of gender equality awareness.

PMID- 22854547
TI  - [A proposal to improve nursing fee differentiation policy for general hospitals
      using profitability-analysis in the national health insurance].
AB  - PURPOSE: The purpose of this study was to propose optimal hospitalization fees
      for nurse staffing levels and to improve the current nursing fee policy. METHODS:
      A break-even analysis was used to evaluate the impact of a nursing fee policy on
      hospital's financial performance. Variables considered included the number of
      beds, bed occupancy rate, annual total patient days, hospitalization fees for
      nurse staffing levels, the initial annual nurses' salary, and the ratio of
      overhead costs to nursing labor costs. Data were collected as secondary data from
      annual reports of the Hospital Nursing Association and national health insurance.
      RESULTS: The hospitalization fees according to nurse staffing levels in general
      hospitals are required to sustain or decrease in grades 1, 2, 3, 4, and 7, and
      increase in grades 5 and 6. It is suggested that the range between grade 2 and 3
      be sustained at the current level, the range between grade 4 and 5 be widen or
      merged into one, and the range between grade 6 and 7 be divided into several
      grades. CONCLUSION: Readjusting hospitalization fees for nurse staffing level
      will improve nurse-patient ratio and enhance the quality of nursing care in
      hospitals. Follow-up studies including tertiary hospitals and small hospitals are
      recommended.

PMID- 22854548
TI  - [Nurses' cardiopulmonary resuscitation performance during the first 5 minutes in
      in-situ simulated cardiac arrest].
AB  - PURPOSE: The purpose of this study was to analyze the cardiopulmonary
      resuscitation skills and teamwork of nurses in simulated cardiac arrests in the
      hospital. METHODS: A descriptive study was conducted with 35 teams of 3 to 4
      registered nurses each in a university hospital located in Seoul. A mannequin
      simulator was used to enact simulated cardiac arrest. Assessment included
      critical actions, time elapsed to initiation of critical actions, quality of
      cardiac compression, and teamwork which comprised leadership behavior and
      communication among team members. RESULTS: Among the 35 teams, 54% recognized
      apnea, 43% determined pulselessness. Eighty percent of the teams compressed at an
      average elapsed time of 108+/-75 seconds with 35%, 36%, and 67% mean rates of
      correct compression depth, rate, and placement, respectively. Thirty-seven
      percent of the teams defibrillated at 224+/-67 seconds. Leadership behavior and
      communication among team members were absent in 63% and 69% of the teams,
      respectively. CONCLUSION: The skills of the nurses in this study cannot be
      considered adequate in terms of appropriate and timely actions required for
      resuscitation. Future resuscitation education should focus on improving the
      quality of cardiopulmonary resuscitation including team performance targeting the
      first responders of cardiac arrest.

PMID- 22854549
TI  - [Effects of a yoga-focused prenatal program on stress, anxiety, self confidence
      and labor pain in pregnant women with in vitro fertilization treatment].
AB  - PURPOSE: The purpose of this study was to identify the effects of a Yoga-focused
      prenatal program on the stress, anxiety, self confidence and labor pain of
      pregnant women who had in vitro fertilization (IVF) treatment. METHODS: A quasi
      experimental study with a non-equivalent control group pretest-posttest design
      was used. The data collection period and meditation program were between January
      9 and August 31, 2009. Forty-six women who were pregnant following IVF, and were
      between 12-20 weeks gestation, participated in the study (23 experimental group,
      23 control group). Data were analyzed using Chi-square test, Mann-Whitney U Test,
      ANCOVA, and Cronbach's alpha coefficients with the SPSS 12.0 for Windows Program.
      RESULTS: Although the sample size was limited, women who participated in the
      program showed statistically significant improvements in stress, anxiety, labor
      pain, and labor confidence for women pregnant after IVF. CONCLUSION: The result
      indicate that this 12-week Yoga-focused educational program can be utilized for
      women pregnant following IVF to reduce their stress, anxiety, and labor pain, and
      to increase delivery confidence. It is suggested that the Yoga-focused
      educational program be offered to every pregnant woman.

PMID- 22854550
TI  - [Factors affecting preparation stage to quit smoking in men].
AB  - PURPOSE: This study was done to investigate factors affecting preparation stage
      to quit smoking in men. METHODS: Based on data from the Community Health Survey
      conducted in Chungbuk Province in 2008, we estimated rates and odds ratio (OR) of
      smoking cessation intention for 2,639 men who were current smokers. Multivariate
      logistic regression analyses were used to identify factors affecting preparation
      stage to quit smoking. RESULTS: Among current male smokers, the rate of smoking
      cessation intention was 17.1%. The OR of factors affecting smoking cessation was
      as follows: Compared to men with middle school education, the OR for rate of
      smoking cessation intention in men with high school education was 1.47 (p=.018),
      and for college or higher, 1.55 (p=.017). Compared to being single, the OR for
      cohabitation after marriage was 1.61 (p=.011) and living alone after marriage,
      2.23 (p=.005). The OR for attempt to quit smoking, exposure to secondhand smoke
      and participation in smoking education were 6.80 (p<.001), 1.32 (p=.020) and 1.69
      (p=.005), respectively. CONCLUSION: Results of this study show that it is
      necessary to decrease exposure to secondhand smoke and to increase participation
      in smoking cessation education targeting current smokers to move them from
      precontemplation or contemplation stage to preparation stage.

PMID- 22854551
TI  - [Development and validation of self-efficacy scale for self-management of breast
      cancer (SESSM-B)].
AB  - PURPOSE: This purpose of this study was to develop and validate a Self-Efficacy
      Scale for Self-Management of Breast Cancer (SESSM-B). METHODS: The SESSM-B was
      developed and validated as follows: Item generation, pilot study, and tests of
      validity and reliability. Twenty-one items were developed through evaluation by
      10 experts and 13 items were finally confirmed through item analysis and factor
      analysis. Psychometric testing was performed with a convenience sample of 303
      women with breast cancer. Data were analyzed using factor analysis, Pearson
      correlation coefficients, and Cronbach's alpha. RESULTS: Five factors evolved
      from the factor analysis, which explained 69.8% of the total variance. The first
      factor 'coping with psycho-informational demand' explained 17.2%, 2nd factor
      'maintenance of healthy lifestyle' 14.5%. 3rd factor 'management of side-effects'
      13.3%, 4th factor 'therapeutic compliance' 12.8%, and 5th factor 'sexual life'
      11.9%. SESSM-B also demonstrated a concurrent validity with health-related
      quality of life scale, EORTC QLQ-C30 & BR23. The internal consistency, Cronbach's
      alpha, was .78, and reliability of the subscales ranged from .61 to .79.
      CONCLUSION: The results of this study suggest that the SESSM-B is an easy,
      reliable, and valid instrument to measure self-efficacy for self-management of
      breast cancer.

PMID- 22854552
TI  - [Risk factors and features of critically ill patients with deep vein thrombosis
      in lower extremities].
AB  - PURPOSE: The purpose of this study was to identify the features, risk scores and
      risk factors for deep vein thrombosis in critically ill patients who developed
      deep vein thrombosis in their lower extremities. METHODS: The participants in
      this prospective descriptive study were 175 adult patients who did not receive
      any prophylactic medication or mechanical therapy during their admission in the
      intensive care unit. RESULTS: The mean age was 62.24 (+/-17.28) years. Men made
      up 54.9% of the participating patients. There were significant differences in
      age, body mass index, and leg swelling between patients who developed deep vein
      thrombosis and those who did not have deep vein thrombosis. The mean risk score
      was 6.71(+/-2.94) and they had on average 4.01(+/-1.35) risk factors. In the
      multiple logistic regression, body mass index (odds ratio=1.14) and leg swelling
      (odds ratio=6.05) were significant predictors of deep vein thrombosis.
      CONCLUSION: Most critically ill patients are in the potentially high risk group
      for deep vein thrombosis. However, patients who are elderly, obese or have leg
      edema should be closely assessed and more than one type of active prophylactic
      intervention should be provided.

PMID- 22854553
TI  - [Effects of A-solution on halitosis and oral status in preoperative NPO
      patients].
AB  - PURPOSE: The aim of this study was to explore the effects of A-solution on
      halitosis and oral status in preoperative NPO patients. METHODS: A nonequivalent
      control group, non-synchronized pretest-posttest design was used in this study.
      The participants in this study were 66 patients who were admitted for gynecologic
      surgery. The experimental treatment was to give oral gargling with A-solution,
      blended essential oils and diluted with distilled water. To identify the
      experimental treatment effects, halitosis, salivary pH, and oral status were
      measured by a portable halitosis detector, visual analogue scale, Bromo Thymol
      Blue (BTB), Bromo Cresol Purple (BCP) test paper and oral assessment guide. Data
      were analyzed using chi2-test, t-test with PASW 18.0 version. RESULTS:
      Participants were homogeneous before experimental treatment. Objective halitosis
      in the experimental group, measured by a portable halitosis detector (t= -8.34,
      p<.001) was significantly lower than the control group. Subjective halitosis was
      significantly lower in the experimental group (t= -9.29, p<.001). Salivary pH was
      significantly different between two groups (t=8.81, p<.001). Oral status was
      significantly better in the experimental group (t= -13.31, p<.001). CONCLUSION:
      These findings indicate that oral gargling using A-solution is effective in
      reducing patient halitosis, and improving oral status.

PMID- 22854554
TI  - [Development and validation of the Korean Nursing Delirium Scale].
AB  - PURPOSE: The aims of this study were to develop and test the validity of the
      Korean Nursing Delirium Scale (Nu-DESC) for older patients in hospital. METHODS:
      The Korean Nu-DESC was developed based on the Nu-DESC (Gaudreau, 2005), and
      revised according to nursing records related to signs and symptoms of older
      patients with delirium (n=361) and the results of a pilot study (n=42) in one
      general hospital. To test the validity of the Korean Nu-DESC, 75 older patients
      whom nurses suspected of delirium from 731 older patients from 12 nursing units
      were assessed by bedside nurses using the Korean Nu-DESC. A Receiver Operating
      Characteristic Curve of the Korean Nu-DESC was constructed with an accompanying
      Area Under the Curve (AUC). RESULTS: Specific examples such as irritable,
      kidding, sleeping tendency, which were observed by bedside nurses in Korea, were
      identified in the five features of signs and symptoms of delirium in the
      instrument. The Korean Nu-DESC was psycho-metrically valid and had a sensitivity
      and specificity of .81-.76 and .97-.73, respectively. The AUC were .89, .74.
      CONCLUSION: Results of this study indicate that the Korean Nu-DESC is well-suited
      for widespread clinical use in busy inpatients settings and shows promise as a
      research instrument.

PMID- 22854555
TI  - [Accuracy, precision, and validity of fever detection using non-invasive
      temperature measurement in adult coronary care unit patients with pulmonary
      catheters].
AB  - PURPOSE: To investigate the accuracy, precision and validity of fever detection
      of tympanic membrane (TM), temporal artery (TA) and axillary temperature (AT)
      compared with pulmonary artery temperature (PA). METHODS: Repeated-measures
      design was conducted for one year on 83 adult cardiac care unit patients with
      pulmonary artery catheters after open heart surgery. Sequential temperature
      measurements were taken three times at 20-minute intervals. Accuracy, precision,
      repeatability, and validity of fever detection were analyzed. RESULTS: Mean
      pulmonary artery temperature was 37.04 degrees C (SD 0.70 degrees C). The mean
      (SD) offsets from PA, with the mean reflecting accuracy and SD reflecting
      precision, were -1.31 degrees C (0.75 degrees C) for TA, -0.20 degrees C (0.24
      degrees C) for TM, and -0.97 degrees C (0.64 degrees C) for AT. Percentage of
      pairs with differences within +/-0.5 degrees C was 9.6% for TA, 19.7% for AT, and
      91.6% for TM. Repeated measurements with all three methods had mean SD values
      within 0.04 degrees C. Sensitivity, specificity, and positive and negative
      predictive values of tympanic measurements were 0.76, 1.0, and 1.0, and 0.90,
      respectively. CONCLUSION: Results show that TM best reflects PA, and is most
      consistent, accurate, and precise. AT tends to underestimate PA, and TA is least
      accurate and precise. Therefore tympanic membrane measurement is a reliable
      alternative to other non-invasive methods of measuring temperatures.

PMID- 22854556
TI  - [Health-related quality of life in Korean patients with rheumatoid arthritis:
      association with pain, disease activity, disability in activities of daily living
      and depression].
AB  - PURPOSE: The purpose of this predictive study was to identify factors affecting
      health related quality of life (HRQoL) in patients with rheumatoid arthritis
      (RA). METHODS: The participants in this study were 131 patients with RA who were
      recruited from the outpatient clinic of a university hospital in Seoul. Disease
      activity in rheumatoid arthritis was evaluated by calculating the Disease
      Activity Score 28. Disability in activities of daily living (ADL) was assessed
      with the Korean Health Assessment Questionnaire, and depression with The Center
      for Epidemiologic Studies Depression Scale. HRQoL was evaluated using The Short
      Form 36 Health Survey. Data were analyzed using descriptive statistics,
      correlation, and hierarchical multiple regression. RESULTS: Pain, disability in
      ADL, disease activity, and depression correlated negatively with physical and
      mental dimensions of HRQoL. But hierachical multiple regression analysis revealed
      that disability in ADL and depression were the only variables negatively
      influencing physical and mental QoL after adjustment for influences of
      sociodemographic variables. CONCLUSION: Results of this study suggest that
      disability in ADL and depression, rather than disease activity and pain have
      profound effects on HRQoL in patients with RA. Further studies are needed to
      assess the predictive ability of disease activity and pain on HRQoL in this
      population.

PMID- 22854557
TI  - [A comparison of the rates of hemolysis and repeated blood sampling using syringe
      needles versus vacuum tube needles in the emergency department].
AB  - PURPOSE: This study was done to compare the rates of hemolysis and repeated
      sampling in blood samples obtained by a syringe needle versus a vacuum tube
      needle. METHODS: A randomized, prospective study was used to evaluate the
      differences between the two blood sampling methods. The study group consisted of
      patients seen in the emergency department (ED) for blood sampling to determine
      electrolyte level. ED patients were randomly assigned to either the syringe group
      or the vacuum tube group. All blood samples were collected by experienced ED
      nurses and hemolysis was determined by experienced laboratory technologists. Data
      were analyzed using Fisher's exact test and binary logistic regression. RESULTS:
      One hundred forty-five valid samples were collected (74 in the syringe group
      versus 71 in the vacuum tube group). 5 of 74 (6.8%) blood samples in the syringe
      group and 8 of 71 (11.3%) in the vacuum tube group hemolyzed. Repeated blood
      sampling occurred for 2 of 74 (2.7%) and 3 of 71 (4.2%) in each group
      respectively. There were no significant differences in rates of hemolysis and
      repeated sampling between two groups (B=1.97, p=.204; B=2.36, p=.345).
      CONCLUSION: Venipuncture with syringe needles can be recommended for ED nurses to
      obtain blood samples.

PMID- 22854559
TI  - Therapeutic penetrating keratoplasty in severe infective keratitis using glycerol
      preserved donor corneas.
AB  - PURPOSE: To report the surgical outcome of therapeutic penetrating keratoplasty
      (TPKP) using glycerol-preserved donor corneas in severe infective keratitis.
      METHODS: Glycerol-preserved corneas were obtained from the recipient corneas of
      the patients who underwent optical penetrating keratoplasty and preserved in
      glycerol. Eight eyes of 8 patients (3 men/5 women; average age, 69.7 years) with
      severe corneal ulcer with perforation were treated with TPKP using glycerol
      preserved corneas. RESULTS: With a mean follow-up time of 31.1 months (range, 9
      58 months), satisfactory anatomical integrity was obtained in 7 patients (87.5%)
      at the end of the follow-up. Eradication of infection without recurrence was
      obtained in 7 eyes (87.5%). The mean reepithelialization time was 10.2 days. One
      patient (12.5%) received secondary optical penetrating keratoplasty. The pre-TPKP
      visual acuity ranged from no light perception to 0.06. After surgery, 4 eyes
      (50%) improved or maintained preoperative visual acuity and four eyes (50%) had
      no light perception but maintained anatomical integrity. One had a recurrent
      infection and needed antibiotics and amniotic membrane graft. One suffered from
      secondary glaucoma and received evisceration 19 months later. CONCLUSIONS:
      Glycerol-preserved donor corneas may be effective substitutes in TPKP to control
      severe infective keratitis and preserve anatomical integrity.

PMID- 22854560
TI  - Serial 3-dimensional computed tomography and a novel method of volumetric
      analysis for the evaluation of the osteo-odonto-keratoprosthesis.
AB  - PURPOSE: To assess the use of serial computed tomography (CT) in the detection of
      osteo-odonto-lamina resorption in osteo-odonto-keratoprosthesis (OOKP) and to
      investigate the use of new volumetric software, Advanced Lung Analysis software
      (3D-ALA; GE Healthcare), for detecting changes in OOKP laminar volume. METHODS: A
      retrospective assessment of the radiological databases and hospital records was
      performed for 22 OOKP patients treated at the National OOKP referral center in
      Brighton, United Kingdom. Three-dimensional surface reconstructions of the OOKP
      laminae were performed using stored CT data. For the 2-dimensional linear
      analysis, the linear dimensions of the reconstructed laminae were measured,
      compared with original measurements taken at the time of surgery, and then
      assigned a CT grade based on a predetermined resorption grading scale. The
      volumetric analysis involved calculating the laminar volumes using 3D-ALA. The
      effectiveness of 2-dimensional linear analysis, volumetric analysis, and clinical
      examination in detecting laminar resorption was compared. RESULTS: The mean
      change in laminar volume between the first and second scans was -6.67% (range,
      +10.13% to -24.86%). CT grades assigned to patients based on laminar dimension
      measurements remained the same, despite significant changes in laminar volumes.
      Clinical examination failed to identify 60% of patients who were found to have
      resorption on volumetric analysis. CONCLUSIONS: Currently, the detection of
      laminar resorption relies on clinical examination and the measurement of laminar
      dimensions on the 2- and 3-dimensional radiological images. Laminar volume
      measurement is a useful new addition to the armamentarium. It provides an
      objective tool that allows for a precise and reproducible assessment of laminar
      resorption.

PMID- 22854561
TI  - Formaldehyde fixation of Drosophila testes.
AB  - This protocol describes formaldehyde fixation of Drosophila testes. The procedure
      preserves chromosome morphology very well, allowing a clear visualization of the
      chromosome condensation-decondensation cycle. It also results in excellent
      preservation of microtubules for immunostaining. The main disadvantage of this
      fixation technique is its poor preservation of cell morphology, as viewed by
      phase-contrast optics. In addition, because it involves a rather hard squashing
      of formaldehyde-fixed testes, it results in meiotic figures which are flatter and
      larger than those obtained using methanol-acetone or paraformaldehyde fixation
      protocols.

PMID- 22854562
TI  - Chromatin staining of Drosophila testes.
AB  - This protocol describes chromatin staining of Drosophila testes. To visualize
      DNA, preparations fixed using methanol-acetone, paraformaldehyde, or formaldehyde
      can be stained with several DNA-binding dyes. If the slides are to be examined
      with a fluorescence microscope equipped with filters that permit ultraviolet (UV)
      excitation, suitable dyes for DNA staining are Hoechst 33258 or 4',6-diamidino-2
      phenylindole (DAPI). If the slides are to be analyzed with a confocal microscope
      not equipped with a UV laser, DNA can be stained with either propidium iodide or
      TOTO-3 iodide.

PMID- 22854563
TI  - Analysis of Drosophila larval feeding response to quinine-adulterated food.
AB  - The food responses of Drosophila larvae offer an excellent opportunity to study
      the genetic and neural regulation of feeding behavior. Compared with fed larvae,
      hungry larvae are more likely to display aggressive foraging, rapid food intake,
      compensatory feeding, and stress-resistant food procurement. Omnivores, including
      humans, tend to avoid noxious or unfamiliar food. Fly larvae avoid bitter
      substances such as quinine. As an increasing amount of quinine is added to an
      otherwise palatable liquid medium containing sugar and inactivated yeast, larvae
      become less likely to consume the tainted food. Larval feeding activity is
      assayed by scoring the percentage of larvae containing dyed food in a large
      portion of the midgut. Defensive foraging behavior can be modulated by
      physiological need and food deprivation significantly increases larval tolerance
      to quinine. Therefore, the larval response to quinine food and its regulation by
      hunger provides a useful paradigm for elucidating the genetic and neural
      regulation of food choice that favors short-term survival. The test described
      here is designed for quantitative assessment of the motivation of individual
      larvae to ingest quinine-adulterated food under different energy states. The test
      is applicable to routine functional testing and larger-scale screening of genetic
      mutations and biologics that might affect food consumption.

PMID- 22854564
TI  - Whole-mount fluorescence in situ hybridization and antibody staining of
      Drosophila embryos.
AB  - Whole-mount RNA in situ hybridizations with digoxigenin-conjugated probes and
      alkaline phosphatase biochemistry have been used widely for many years to map
      expression pattern domains in the Drosophila embryo. To capitalize on the number
      of molecular markers in the central nervous system (CNS) and to enable expression
      analysis at the single-cell level, fluorescence in situ hybridization procedures
      are becoming standard. This protocol describes methods for the simultaneous
      detection of RNA and protein using fluorescence in Drosophila embryos. It uses
      the tyramide signal amplication (TSA) system from PerkinElmer to amplify a
      horseradish peroxidase (HRP) signal. By combining this technology with an HRP
      conjugated antidigoxigenin antibody, we can detect standard antidigoxigenin RNA
      probes fluorescently.

PMID- 22854565
TI  - Fluorescence-activated cell sorting (FACS) of fluorescently tagged cells from
      zebrafish larvae for RNA isolation.
AB  - This article describes a procedure for the dissociation of zebrafish (Danio
      rerio) embryos to produce a suspension of single cells that is suitable for
      fluorescence-activated cell sorting (FACS). The method has been applied to
      embryos at stages from 14 h post fertilization (hpf) to larvae at 5 d post
      fertilization (dpf), and it has also been successfully used for isolating
      fluorescently tagged neurons from whole dissociated embryos and early larvae. The
      cell collection procedures described in this protocol may also be adapted for
      older embryos and juvenile zebrafish. RNA can be extracted from the sorted cells
      and used for subsequent quantitative real-time PCR (qRT-PCR), microarrays, or
      next-generation sequencing (NGS) experiments.

PMID- 22854566
TI  - In vivo electroporation of E1 chick embryos.
AB  - In ovo electroporation of chick embryos at ages >= E2 is simple to conduct and
      widely used to manipulate gene function. However, in ovo electroporation at early
      E1 stages has so far been unsuccessful because of unacceptable levels of tissue
      damage and embryonic lethality. Early E1 manipulations in the chick have
      therefore relied on in vitro electroporation, posing problems for morphogenetic
      studies in which the long-term preservation (>24 h) of three-dimensional tissue
      organization is critical. This article describes a simple technique for in vivo
      electroporation of E1 embryos as young as Hamburger-Hamilton stage 4 (HH4). It
      uses thin microelectrodes and low voltages, which permit precise localization of
      gene misexpression while causing minimal tissue damage and embryonic lethality.
      Critically, it does not depend on the presence of a lumen for DNA injections and
      can easily be adapted for a wide variety of tissues.

PMID- 22854567
TI  - Delivery of recombinant alphavirus into hippocampal slice tissue culture.
AB  - The alphaviruses Semliki Forest virus (SFV) and Sindbis virus (SIN) have been
      used frequently as expression vectors in vitro and in vivo. Usually, these
      systems consist of replication-deficient vectors that require a helper vector for
      packaging of recombinant particles. Replication-proficient vectors have also been
      engineered. Alphaviral vectors can be used as nucleic-acid-based vectors (DNA and
      RNA) or infectious particles. High-titer viral production is achieved in <2 d.
      The broad host range of alphaviruses facilitates studies in mammalian and
      nonmammalian cell lines, primary cells in culture, and in vivo. The strong
      preference for expression in neuronal cells has made alphaviruses particularly
      useful in neurobiological studies. Unfortunately, their strong cytotoxic effect
      on host cells, relatively short-term transient expression patterns, and the
      reasonably high cost of viral production remain drawbacks. However, novel mutant
      alphaviruses have shown reduced cytotoxicity and prolonged expression. This
      protocol describes gene delivery of recombinant alphavirus to hippocampal slice
      cultures. Organotypic slices are covered by a layer of glial cells that impedes
      the penetration of viral particles to the neurons. Thus, viral particles should
      be injected manually into the extracellular space of the tissue.

PMID- 22854568
TI  - In vivo administration of recombinant alphavirus into rodents.
AB  - The alphaviruses Semliki Forest virus (SFV) and Sindbis virus (SIN) have been
      used frequently as expression vectors in vitro and in vivo. Usually, these
      systems consist of replication-deficient vectors that require a helper vector for
      packaging of recombinant particles. Replication-proficient vectors have also been
      engineered. Alphaviral vectors can be used as nucleic-acid-based vectors (DNA and
      RNA) or infectious particles. High-titer viral production is achieved in <2 d.
      The broad host range of alphaviruses facilitates studies in mammalian and
      nonmammalian cell lines, primary cells in culture, and in vivo. The strong
      preference for expression in neuronal cells has made alphaviruses particularly
      useful in neurobiological studies. Unfortunately, their strong cytotoxic effect
      on host cells, relatively short-term transient expression patterns, and the
      reasonably high cost of viral production remain drawbacks. However, novel mutant
      alphaviruses have shown reduced cytotoxicity and prolonged expression. This
      protocol describes stereotactic microinjection of recombinant alphavirus into
      rodents. Administration can be performed without any purification or
      concentration of viral stocks. However, filter-sterilization is recommended to
      ensure that cell debris or other contaminants are not present.

PMID- 22854569
TI  - Labeling Golgi with fluorescent ceramides.
AB  - The Golgi may be considered a principal organizer of macromolecular traffic in
      the cell because many molecules, such as secreted proteins, glycoproteins,
      glycolipids, and plasma membrane glycoproteins, pass through the Golgi during
      their maturation. The fluorescent probes used to tag the Golgi make use of this
      function for labeling by using a fluorescent ceramide. In this protocol, two
      probes for labeling the Golgi are presented: a classic NBD-ceramide and a BODIPY
      ceramide probe that is more resistant to photobleaching.

PMID- 22854570
TI  - Cellular bioluminescence imaging.
AB  - Bioluminescence imaging of live cells has recently been recognized as an
      important alternative to fluorescence imaging. Fluorescent probes are much
      brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide
      much better spatial and temporal resolution and much better contrast for
      delineating cell structure. However, with bioluminescence imaging there is
      virtually no background or toxicity. As a result, bioluminescence can be superior
      to fluorescence for detecting and quantifying molecules and their interactions in
      living cells, particularly in long-term studies. Structurally diverse luciferases
      from beetle and marine species have been used for a wide variety of applications,
      including tracking cells in vivo, detecting protein-protein interactions,
      measuring levels of calcium and other signaling molecules, detecting protease
      activity, and reporting circadian clock gene expression. Such applications can be
      optimized by the use of brighter and variously colored luciferases, brighter
      microscope optics, and ultrasensitive, low-noise cameras. This article presents a
      review of how bioluminescence differs from fluorescence, its applications to
      cellular imaging, and available probes, optics, and detectors. It also gives
      practical suggestions for optimal bioluminescence imaging of single cells.

PMID- 22854571
TI  - Automated lineage and expression profiling in live Caenorhabditis elegans
      embryos.
AB  - Describing gene expression during animal development requires a way to
      quantitatively measure expression levels with cellular resolution and to describe
      how expression changes with time. Fluorescent protein reporters make it possible
      to measure expression dynamics in live cells by time-lapse microscopy, but it can
      be challenging to identify expressing cells in complex tissues and to compare
      expression across organisms. This protocol describes how to use automated lineage
      analysis to identify cells in Caenorhabditis elegans embryos expressing
      fluorescent reporters and how to quantify that expression with cellular
      resolution. Because C. elegans develops through an invariant pattern of cell
      divisions, every cell's identity and future fate can be predicted from its
      pattern of previous cell divisions. Automated analysis of images collected from
      embryos expressing a fluorescent histone transgene in all cells allows lineage
      tracing and cell identification. This provides a scaffold with which to describe
      expression of a second color reporter such as a fusion of a second fluorescent
      protein to a gene of interest or its regulatory sequences. These methods can also
      be used for analysis of reporter expression, cell division timing, and cell
      position in genetically perturbed embryos. The protocol describes how to prepare
      C. elegans strains containing nuclear-expressed fluorescent reporters, collect
      images of appropriate quality from embryos, perform automated lineage analysis,
      manually edit and curate the lineage, and, finally, extract and display reporter
      signals.

PMID- 22854572
TI  - Introduction to stereology.
AB  - Just as astrology became astronomy and alchemy became chemistry through the
      application of mathematics, descriptive anatomy can be expected to become more
      and more quantitative in nature. This article describes the basics of stereology,
      which provides meaningful quantitative descriptions of the geometry of three
      dimensional (3D) structures from measurements that are made on two-dimensional
      (2D) images. With precise mathematical descriptions such as those that can be
      obtained with unbiased stereological techniques, it will be possible to make
      concise descriptions of the relationships between structure and function, of the
      dynamics of structure, and to reassert the importance of quantitative morphology
      as an essential part of the evaluation of biological tissues.

PMID- 22854573
TI  - Acousto-optical deflector-based patterned ultraviolet uncaging of
      neurotransmitter for the study of neuronal integration.
AB  - The method of patterned photoactivation is a natural fit for the study of
      neuronal dendritic integration. Photoactivatable molecules that influence a wide
      range of extracellular and intracellular neurophysiological functions are
      available. The choice of photosensitive molecules depends on the research
      question and will influence the design of the experimental apparatus. This
      article describes an acousto-optical deflector (AOD)-based system for rapid
      ultraviolet (UV) photolysis in arbitrary spatial and temporal patterns. Some
      basics of caged neurotransmitters and the theory of operation of AODs are
      covered, as are descriptions for implementing the system.

PMID- 22854574
TI  - Construction, alignment, and implementation of an acousto-optical deflector-based
      system for patterned uncaging with ultraviolet light.
AB  - The method of patterned photoactivation is a natural fit for the study of
      neuronal dendritic integration. Photoactivatable molecules that influence a wide
      range of extracellular and intracellular neurophysiological functions are
      available. The choice of photosensitive molecules depends on the research
      question and will influence the design of the experimental apparatus. An acousto
      optical deflector (AOD)-based system can be used for rapid ultraviolet (UV)
      photolysis in arbitrary spatial and temporal patterns. Photolysis-activated
      "caged" diffusible molecules or newer light-sensitive membrane proteins can be
      used in this system. This protocol describes the addition of a UV beam for
      uncaging to a homebuilt two-photon microscope. The goal is to get UV light from
      the light source (laser) to the approximate center of the objective's back
      aperture, passing through a pair of perpendicularly oriented AODs along the way.
      The protocol also describes the fine alignment of the UV beam and the
      implementation of AOD-based beam steering. Performing the final alignment with
      the beam passing through the AODs will ensure that the system is optimized for
      the idiosyncrasies of the crystals.

PMID- 22854575
TI  - Preparing, handling, and applying caged compound solutions for acousto-optical
      deflector-based patterned uncaging with ultraviolet light.
AB  - The method of patterned photoactivation is a natural fit for the study of
      neuronal dendritic integration. Photoactivatable molecules that influence a wide
      range of extracellular and intracellular neurophysiological functions are
      available. The choice of photosensitive molecules depends on the research
      question and will influence the design of the experimental apparatus. An acousto
      optical deflector (AOD)-based system can be used for rapid ultraviolet (UV)
      photolysis in arbitrary spatial and temporal patterns. This protocol describes
      how to prepare caged neurotransmitter compound solutions for use in this system
      and discusses options for introducing caged compounds into an experimental
      preparation.

PMID- 22854576
TI  - Treating anxiety disorders with virtual reality exposure therapy.

PMID- 22854577
TI  - [Eligibility of schizophrenia inpatients to participate in clinical trials].
AB  - INTRODUCTION: This study assesses the potential eligibility of patients admitted
      to a psychiatric hospitalisation unit to take part in the major clinical trials
      based on schizophrenia treatment in clinical practice (CATIE, CUtLASS and
      EUFEST). MATERIAL AND METHODS: A retrospective evaluation by consulting the
      medical records of 241 subjects (59.8% males and 40.2% females, mean age 39.7+/
      13.0 years), admitted consecutively over one year to psychiatric hospitalisation
      unit with a diagnosis of schizophrenia or another psychosis. The influence of the
      factors involved in the non-eligibility in each of the clinical trials is
      analysed using logistic regression analysis. RESULTS: Only 20.7%, 22.3%, and
      22.5% of patients with schizophrenia or another psychosis would be eligible to
      participate in the CATIE, CUtLASS and EUFEST studies, respectively. The main
      factors involved in the non-eligibility were polytherapy with anti-psychotics (2
      or more) (Odds Ratio (OR): 7.64, 95% confidence interval (CI): 3.06-19.06,
      P<.001), mental retardation (OR: 16.67, 95% CI: 1.75-166.67, P=.014), and
      resistance, intolerance or contraindication to any of the anti-psychotics of the
      study (OR: 3.68, 95% CI: 1.13-11.99, P=.030). CONCLUSIONS: Three out of every
      four patients with schizophrenia or another psychosis admitted to a psychiatric
      hospitalisation unit are not represented in the major clinical trials on
      schizophrenia treatment.

PMID- 22854578
TI  - [Adaptation of the Hinting Task theory of the mind test to Spanish].
AB  - INTRODUCTION: Many studies have found that patients with schizophrenia have a
      deficit in theory of mind. Some authors associate this deficit with the presence
      of symptoms, while others maintain that it can also be observed in patients in
      the remission phase. There is no reference test to assess theory of mind in
      schizophrenia, although one of the most used is the Hinting Task. The aim of the
      present study consists of adapting and validating, in Spanish, the 10 histories
      that make up this test. MATERIAL AND METHODS: The study was conducted on a sample
      of 39 control subjects and 40 patients with schizophrenia. The internal
      consistency and the between-observer reliability and test-retest were assessed in
      both sample groups. The performance of the patients and control subjects were
      also compared. RESULTS: Good reliability data was obtained in the inter-observer
      and test-retest in the two samples. On the other hand, the internal consistency
      was somewhat low for all of the 10 histories. For this reason, and starting from
      a previous study, a reduced version of 5 histories was prepared, which showed
      good internal consistency. The patients with schizophrenia obtained a
      significantly lower score than the control subjects in 8 out of the 10 histories.
      CONCLUSIONS: The reduced Spanish version of the Hinting Task demonstrated good
      psychometric properties. When compared to the control group, the patients with
      schizophrenia had a deficit in theory of mind.

PMID- 22854579
TI  - [Early detection of hypomania episodes in patients with affective disorder].
AB  - INTRODUCTION: Bipolar disorder (BP) is one of the major causes of disability in
      the world. Epidemiological studies suggest that this disorder could be under
      diagnosed owing to the difficulty in detecting hypomania episodes. The detection
      of present and past episodes of hypomania could help in the diagnosis and
      appropriate treatment of this disorder. The Hypomania Check List (HCL-32) is a
      questionnaire validated into Spanish and designed to detect past and present
      hypomania episodes in the psychiatric patient population. MATERIAL AND METHODS: A
      total of 128 patients over 18 years old and diagnosed with type I bipolar (BP-I)
      disorder (n=1), type II bipolar (BP-II) disorder (n=30), major depression (MD)
      (n=57), anxiety disorders (AD) (n=15) were selected, along with a control group
      (C) (n=25). The patients were diagnosed according to the diagnostic criteria of
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IVTR). Screening for hypomania episodes was carried out by applying
      the HCL-32 scale. RESULTS: The area under the ROC curve was 0.65 with a 95%
      confidence interval (CI) of 0.55-0.75. The chosen cut-off point of the HCL-32 was
      15. The values for the sensitivity (Se), specificity (Sp), positive predictive
      values (PPV) and negative predictive values (NPV), and the prevalence (P) of
      hypomania episodes in the patients of the UP depression, for a cut-off point of
      15 were: Se =71.4%, 95% CI; 57.8, 85.1, Sp =45.8%, 95% CI; 34.5-57.1, PPV=43.75%,
      95% CI; 32.25-55.25), NPV:73.08%, 95% CI; 60.06-86.09) and P=67.2%. CONCLUSIONS:
      The HCL-32 is a very sensitive, but not very specific, screening tool. This could
      partly explain the high proportion of hypomania episodes detected in our sample.
      Unlike previous studies, our sample is heterogeneous (from different
      environments) and at a more severe and unstable clinical level. Future research
      should develop more specific measuring tools, and with greater external
      validation, for hypomania episodes.

PMID- 22854580
TI  - [Opinions and beliefs of the Spanish population on serious mental illnesses
      (schizophrenia and bipolar disorder)].
AB  - INTRODUCTION: To find out the opinions, beliefs and concerns of the Spanish
      population on serious mental diseases: schizophrenia and bipolar disorder.
      MATERIAL AND METHODS: An ad-hoc questionnaire was constructed for the survey. A
      panel of seven experts extracted the contents. The Societies that involved were:
      ASAENES, ABBA, FEAFES-ANDALUCIA, AMAFE, and AFAEM-5 advocacy societies were also
      involved. The questionnaire contained 12 questions about: knowledge of the
      diseases, diagnostic difficulties, symptoms, triggering factors, interference,
      treatments and effectiveness, beliefs and concerns. The questionnaire was
      administered during the IV Campaign of Social Awareness about Serious Mental
      Illness (Madrid and Seville, September-October 2009). RESULTS: A total of 5,473
      questionnaires were collected, 55.8% in Seville. The majority (66.2%) of the
      sample were women, and the mean age was 35 years (SD=14.5). Both illnesses were
      known by 82% of the population, but 51% did not known any symptom of
      schizophrenia. Other notable opinions were; they are difficult to diagnose (59%),
      they were not diagnosed due to social rejection (27%), interfered quite a lot
      with daily life (49%) or prevented a normal life (42%), the effective treatments
      are psychological (72%). Beliefs were: social rejection, family burden, and
      patient suffering. Concerns included: dangerousness, social rejection, lack of
      information, and scarcity of resources. CONCLUSIONS: There is a lack of knowledge
      of the symptoms. The majority do not know about specific symptoms and highlight
      the negative ones. Combined pharmacological-psychological treatment is believed
      to be most effective. Social stigma and family and personal burden are concerns.

PMID- 22854581
TI  - [Use of the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and
      depression in fibromyalgia patients].
AB  - INTRODUCTION: The HADS is a questionnaire widely used to evaluate anxiety and
      depression, although its use in fibromyalgia patients has not yet been reported.
      The aim of this study is to know the usefulness of the HADS to evaluate the
      emotional aspects related to fibromyalgia patients. METHODS: This paper studies a
      sample of 301 fibromyalgia patients. The scientific goodness of the questionnaire
      is analyzed, and its structure is compared with other models by confirmatory
      factor analysis. Two external severity indices are used, number of tender points
      and patient's employment situation. RESULTS: The results show higher levels of
      anxiety than in other disorders, adequate reliability and a three-factor model
      with better statistical fit. Nevertheless, this structure was not shown more
      useful than the two-factor structure for the external criteria studied.
      CONCLUSIONS: The HADS has been shown to be a useful tool for exploring the
      presence of anxiety and depression in fibromyalgia patients and that the number
      of tender points does not seem to be related to the severity of the psychological
      aspects measured by the HADS in our sample, while there does seem to be a
      correspondence between psychological condition and absence from work.

PMID- 22854582
TI  - Anxiety disorder symptoms in children and adolescents: differences by age and
      gender in a community sample.
AB  - INTRODUCTION: Anxiety symptoms in childhood and adolescence are an important risk
      factor for developing anxiety disorders in subsequent development stages. This
      study examines the frequency and characteristics of the symptoms of the principal
      anxiety disorders in children and adoloscents using a self-report questionnaire
      based on the diagnostic categories of the American Psychiatric Association (APA)
      manual. MATERIAL AND METHODS: A cross-sectional, non-interventional study was
      conducted on 2522 children and adolescents form 8 to 17 years (49% males),
      enrolled from different schools in the Province of Alicante who completed the
      Spence Children's Anxiety Scale. RESULTS: The mean score obtained on the scale
      (range: 0-114) was 25.15 (standard deviation (SD)=13.54). More than one in four
      (26.41%) of the children and adolescents showed high scores in any anxiety
      disorder. The anxiety symptoms due to separation were the most frequent in the
      sample (5.5%), followed by physical fears (5.1%). Girls scored significantly
      higher in all disorders (P<.001), except in obsessive-compulsive disorder.
      Differences were found as regards age in all disorders, except physical fears,
      but the effect sizes were only in anxiety due to separation, which decreased with
      age, and generalised anxiety, which was higher in adolescents than in children.
      CONCLUSIONS: From the mental health perspective, it is important to be able to
      detect anxiety symptoms in children from 8 years onwards, in order to intervene
      early and prevent the development of anxiety disorders in later life.

PMID- 22854583
TI  - Quality of life of schizophrenia patients of Aymaran ethnic background in the
      north of Chile.
AB  - OBJECTIVE: To describe the quality of life of patients of Aymaran descent with
      schizophrenia and analyse the differences with patients of non-Aymaran descent.
      METHOD: The study included 45 patients who attended the Mental Health Services in
      Arica, Chile. The Positive and Negative Syndrome Scale (PANSS) and the Seville
      Quality of Life Questionnaire (SQoLQ) were used. RESULTS: The patients of the
      study showed moderate quality of life levels, with a strong association with the
      negative syndrome and the general psychopathology of the disorder. No significant
      differences were found in the quality of life dimensions as regards ethnic
      background. CONCLUSIONS: The results found demonstrate that the integration of
      patients in the Community Health Services is positively associated as regards
      their quality of life. The integration of the caregivers is considered essential
      in the treatments administered.

PMID- 22854584
TI  - Neuronal migration, apoptosis and bipolar disorder.
AB  - Bipolar disorder, like the majority of psychiatric disorders, is considered a
      neurodevelopment disease of neurodevelopment. There is an increased rate of
      neuronal birth and death during this development period. In the particular case
      of the processes that determine neuronal death, it is known that those neurons
      that establish connections have to be removed from the central nervous system.
      There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar
      disorder, accompanied by overexpression of proapoptic genes. There is also an
      alteration in the expression of molecules that mediate in the migration of these
      neurons and their inclusion in functional synapsis during the foetal stage. The
      role of these molecules in the neuronal death pathways by apoptosis will be
      reviewed here in an attempt to establish biological hypotheses of the genesis of
      bipolar disorder.

PMID- 22854585
TI  - Current update on the endovascular management of intracranial aneurysms.
AB  - Rapid technological advances in the endovascular field has revolutionized the
      treatment of intracranial aneurysms. Since the Food and Drug Administration
      approval of Guglielmi detachable coils in 1995, a variety of newer coils with
      different design and physical properties such as complex coils, stretch resistant
      and bioactive coils, have become available promising to increase packing density
      and decrease aneurysmal recurrence and recanalization rates. Treatment of wide
      neck intracranial aneurysms has improved with availability of compliant balloons
      and newer intracranial assist devices. Emerging technology such as flow diverters
      hold promise in treatment of large and difficult to treat intracranial aneurysms.
      Liquid embolic agent (Onyx HD 500) offer a novel, safe and effective adjunctive
      treatment option when used in combination with coils with stent and/or balloon
      assist technique. Endovascular treatment options have vastly expanded the
      armamentarium of neurosurgeons allowing safe and durable treatment of aneurysms
      previously amenable to clipping only.

PMID- 22854586
TI  - Clip occlusion versus coil embolization for the treatment of cerebral aneurysms.
AB  - Advances in the endovascular treatment of intracranial aneurysms since the advent
      of detachable coil embolization continue to expand the spectrum of lesions
      amenable to minimally invasive therapy. The feasibility of treating a given
      cerebral aneurysm by a given open or endovascular modality does not necessarily
      make such an approach the optimal choice. Rather, any given cerebral aneurysm and
      patient should be carefully analyzed on a multitude of parameters which are based
      on available adjunctive technology, aneurysm morphology and characteristics,
      endovascular vs. microsurgical accessibility, and long-term angiographic outcome.
      In addition to patient age, co-morbid conditions, lesion size and attendant risk,
      one must also consider patient preference with respect to length of hospital
      stay, recovery duration and required follow-up and radiographic assessments. The
      relentless improvements in minimally invasive embolization therapies ranging from
      coiling with adjunctive balloon and stent support to the emerging role of flow
      diversion must be balanced against the lower cost and complexity associated with
      longitudinal clinical and radiographic follow-up requirements of microsurgical
      clipping. This review will consider the various factors involved in the
      determination of optimal modality choice based on an assessment of clinical,
      morphological and anatomical considerations. In this rapidly evolving field, the
      quest for maximizing protection from aneurysm rupture at the lowest neurological
      cost dictates that a balance be maintained between technical virtuosity and
      procedural safety of either microsurgical clipping or endovascular repair to
      insure that the advantages of the selected modality not be negated by its
      associated shortcomings.

PMID- 22854587
TI  - An update on traumatic brain injuries.
AB  - Severe traumatic brain injury (TBI) represents a major cause of neurological
      mortality and morbidity throughout the world. Several challenges have been faced
      in the conduct of clinical research in TBI in past decades, including inclusion
      of a broad heterogeneity of injuries, difficulties with standardization and
      consistency of complex medical management, and lack of sophisticated outcomes
      measures to sufficiently detect differences in outcomes. Consequently, evidence
      based guidelines for targeted therapeutic approaches remain for the most part at
      the level of Class II or III evidence. Harnessing the power of computing is
      paramount to our understanding of different prognostic groups in order to devise
      treatments of the future. Multimodality bedside monitoring of various
      physiological parameters and events can be deployed in the intensive care unit
      (ICU) but better data repositories and analytics are required. Recent
      developments in neuroimaging and definition of potential genetic and biological
      markers in TBI are also aiding in the sub-categorization of patients into finer
      diagnostic and prognostic groups. Using mathematical prediction models
      incorporating the plethora of data gathered, future research will provide means
      of tailoring therapies to individuals based upon best evidence in populations
      similar to them, and according to their own biological and physiological
      situation.

PMID- 22854588
TI  - Current use of biologic graft extenders for spinal fusion.
AB  - Use of biologic graft extenders in spinal fusions is increasing. Multiple
      allograft alternatives exist to the "gold-standard" autologous bone grafting. The
      ideal graft extender is osteoconductive, osteoinductive and has osteogenic
      potential. While the ideal graft extender has yet to be found, available bone
      graft extenders have varying degrees of predominantly osteoconductive and
      osteoinductive properties. This review will provide an update on available graft
      extenders including bone morphogenetic proteins, mesenchymal stem cells, and
      demineralized bone matrix. The goal is to provide a review of the current use in
      spinal fusions and future directions in biologics for spinal fusion.

PMID- 22854589
TI  - A psychiatric primer for the functional neurosurgeon.
AB  - There is increasing attention in the neurosurgical literature towards surgery,
      specifically deep brain stimulation (DBS), for psychiatric indications. Several
      positive trials have spurred intense investigation and research in this area,
      owing to rapid advances in the neurosciences. As a result, the scope of
      neurosurgical practice is evolving to now include disorders that weren't
      traditionally in the purview of the average functional neurosurgeon. Further,
      functional neurosurgeons are now being charged with taking care of patients as
      part of a multi-disciplinary group that includes psychologists and psychiatrists.
      As DBS for psychiatry continues to evolve, and as further indications are
      explored, it is incumbent on neurosurgeons who treat these disorders to
      familiarize themselves with current standards of diagnosis and treatment. Just as
      the movement disorder surgeon should be familiar with the biology, physiology,
      diagnosis and treatment of Parkinson's disease, so they should become familiar
      with similar aspects of commonly referred psychiatric conditions. Specifically,
      much of the interest in the DBS literature currently surrounds major depression,
      obsessive-compulsive disorder and Tourette's syndrome. Here, we review the
      epidemiology, diagnostic criteria, hypothesized neurocircuitry and current
      treatments, both medical and surgical of each of these conditions to serve as a
      centralized, introductory primer for the practicing functional neurosurgeon.

PMID- 22854590
TI  - Stem cells based therapy in high grade glioma: why the intraventricular route
      should be preferred?
AB  - AIM: Mesenchymal stem cells (MSCs) migrate in response to chemokines and possess
      extensive tropism for experimental glioma. Antitumor effects have been reported
      following intracranial and intravenous administration of gene-modified MSCs.
      Among the different routes for cell transplant, the intraventricular (IV)
      approach found very little employment in comparison with intraparenchymal,
      intratumoral and intravenous administration protocols. Nevertheless, IV
      transplantation offers advantages in terms of cells viability and distribution
      toward target sites, opening interesting opportunities for its clinical
      application. METHODS: Using a rat glioma model, we investigated migratory
      capacity, tumor tropism, distribution and differentiation of MSCs following IV
      administration. RESULTS: Transplanted MSCs create niches of viable cells in the
      subventricular zone and can be stimulated to migrate to sites of tumor
      infiltration. MSCs seemed not to be involved in tumor growth and angiogenesis.
      CONCLUSION: We speculate that the IV route can be used to achieve a kind of
      reservoir of self-renewal cells, potentially active against the spread of cancer
      cells. Further studies are needed to shed light on MSCs distribution close to the
      ventricular wall, in order to define their lifespan and their capacity to migrate
      towards new-enhancing foci time after implantation.

PMID- 22854591
TI  - Traumatic brain injury in the elderly: considerations in a series of 103 patients
      older than 70.
AB  - AIM: Mortality and morbidity due to brain injury in the elderly population is a
      growing clinical problem: among older patients, those >70 years have a
      considerably higher risk both in terms of mortality and morbidity. Thereafter,
      the reasons influencing outcome have not been clearly examined: in the present
      study we addressed these questions considering the main clinical characteristics
      exerting a significant impact on the outcome of patients aged > 70, with emphasis
      for the severity of brain injury and anticoagulant (CAW) treatments. METHODS: We
      performed a retrospective analysis of 103 consecutive isolated head injury
      patients older than 70, admitted at our Department in the period November 2004
      November 2009. The clinical variables considered were as follow: age, sex, type
      of TBI, GCS, pre-TBI use of anti-coagulants (aspirin, warfarin, clopidogrel), INR
      at admission (INR values were subdivided in values >1.25 as at risk for
      hemorrhagic events and <1.25 as normal), initial CT scan classification looking
      at the presence of subarachnoid hemorrhage (t-SAH) or mass lesions; the main
      outcome measure was the Glasgow Outcome Scale. RESULTS: The most frequent cause
      of TBI was accidental fall (65%): 39 were in CAW therapies and in 36 cases the
      cause of falling down injury was recorded due to a sincopal event (arterial
      hypotension, atrial fibrillation); in the older patients an accidental fall is
      significantly related to the TBI, while in the patients aged 70-75 years, TBI is
      related to a traffic accident (P=0.002). Moreover the cause of TBI correlates
      with the CAW treatment, the accidental fall being significantly more frequent in
      patients in CAW treatment (P=0.003). Overall mortality rate is significantly
      related to an elevated INR class, to presence of t-SAH (16/50 patients) and
      subdural hematoma (26/46). CONCLUSION: The results of the present study show that
      in a population of patients aged > 70, TBI is a high risk event if patient has
      concurrent treatment with CAW therapies and if an accidental fall is the cause of
      TBI. In these cases the finding of t-SAH represents a high-risk parameter for
      mortality but not for morbidity.

PMID- 22854592
TI  - Survival prognostic factors in patients with glioblastoma: our experience.
AB  - AIM: Approximate survival for glioblastoma is less than 1 year. Age, histological
      features and performance status at presentation represent the three statistically
      independent factors affecting longevity. The purpose of the study was to assess
      the role of surgery and to analyze prognostic factors in our patients operated
      for glioblastoma. METHODS: We evaluated in 56 patients operated for glioblastoma
      their depressive and performance status in the preoperative and postoperative
      time. Moreover we analyzed the extent of surgery, the site and the size of
      lesions. RESULTS: Median overall survival was 17 months. An age of >=60 years
      (P<0.03), a preoperative Karnofsky Performance Status KPS<=70 (P=0.04), a
      subtotal tumor resection (P<0.001), a tumor size >5 cm (P=0.01), and no
      postoperative adjuvant treatment (P=0.01) were associated with the worst
      prognosis. Before surgery we found the presence of depression in 10 patients with
      a significative reduction of mean Back Depression Inventory scores after tumor
      resection (P=0.03). Finally, a KPS<=70 was significantly associated with an
      increased incidence of depression in the postoperative time. CONCLUSION: Tumor
      size, total resection and affective disorders were identified as predictors of
      survival in our series of patients with glioblastoma in addition to age and KPS
      score. In our opinion an early diagnosis and the use of specific safeguards in
      the operating room contribute to have an extension of the tumor progression time
      and median survival.

PMID- 22854594
TI  - Intraosseous hemangioma of the clivus: a case report and review of the
      literature.
AB  - Intraosseous hemangiomas are benign vascular tumors that are encountered most
      commonly in vertebrae and rarely in the skull. When presenting in the skull, they
      are commonly found in the calvarium in frontal and parietal bones and seldom in
      the skull base. We encountered a patient with an incidental finding on magnetic
      resonance imaging (MRI) of an enhancing lesion in the clivus. Here we report an
      unusual location of a clival intraosseous hemangioma. A 62 year old man worked up
      for carpal tunnel syndrome had imaging of his cervical spine that revealed an
      enhancing clival lesion, which extended into the left occipital condyle.
      Endoscopic endonasal biopsy was performed on the abnormality revealing a
      capillary hemangioma. Patient tolerated the biopsy well and no further surgical
      intervention is indicated at this time. Patient will be followed at six month
      intervals. Primary intraosseus hemangiomas of the skull are extremely rare and
      usually occur in the calvarium. This is one of the few reported case of an
      intraosseus hemangioma in the clivus. We present this case in part because it is
      unusual, but more importantly, with the wider use of MRI, it is likely that these
      lesions will be discovered more frequently, and conceivably confused for more
      dangerous lesions.

PMID- 22854593
TI  - Nimodipine can diminish oxidative stress in patients with severe head trauma.
AB  - AIM: Antioxidative effect of nimodipine was investigated in patient with severe
      head trauma. METHODS: The patients in group A were treated according to the
      standard procedures without nimodipine. Other patients in group B were treated
      with standard procedures plus intravenous nimodipine for a week. Three times per
      day, blood samples were taken from internal jugular venous saturation probe and
      central venous catheter for a week. The levels of malondialdehyde (MDA), reduced
      glutathione (GSH), nitrite, and nitrate, ascorbic acid, retinol and beta-carotene
      in the serum were measured. RESULTS: MDA levels in group B were significantly
      lower than those in the group A (P<0.05). As for GSH levels, it was observed that
      there was a significant increase in GSH levels in group B when compared to those
      in group A (P<0.01). Comparison of nitrate and nitrite levels in the serum of
      patient groups showed that these parameters were significantly higher in group B
      than those in group A (P<0.01). It was seen that there were a significant
      increase in ascorbic acid (P<0.01) and beta-carotene (P<0.05) levels in group B
      when compared to those in group A. Values of retinol levels were slightly higher
      in group B than that of group A, and there was no significant difference between
      the groups. CONCLUSION: Severe head trauma may increase oxidative stress.
      Administration of nimodipine may prevent the oxidative stress and may augment
      endogenous antioxidative defense systems in patients with severe head trauma.

PMID- 22854595
TI  - Stem cell transplantation into the intraventricular space via an Ommaya reservoir
      in a patient with amyotrophic lateral sclerosis.
AB  - Stem cells have been highlighted for a possible clinical trial in amyotrophic
      lateral sclerosis (ALS), and have been employed in SOD1 mice and ALS patients.
      Human trials for stem cell transplantations have used intrathecal route by lumbar
      puncture. However, stem cells introduced via lumbar injection would tend to sink
      downwards rather than ascending to the brain and cervical and thoracic spinal
      cord. Therefore, we adopted for intraventricular injection via an Ommaya
      reservoir, and wished to test the practicality of intraventricular stem cell
      injection in ALS. In the case presented autologous mesenchymal stromal cells
      (MSCs) were isolated from the bone marrow of a male patient with ALS who
      underwent insertion of an Ommaya reservoir. Expanded MSCs (hBM-MSCs: dose of 1 X
      106 cells/kg) were suspended in autologous CSF and directly transplanted into the
      ALS patient's lateral ventricle via the Ommaya reservoir. Clinical, laboratory,
      and radiographic evaluation of the patient revealed no serious adverse effects
      related to the stem cell therapy. Intraventricular injection with an optimized
      number of cells is safe, and is a potential route for stem cell therapy in
      patients with ALS. Intraventricular injection via an Ommaya reservoir makes
      repetitive injection of stem cells easy and reliable even in far advanced ALS
      patients.

PMID- 22854596
TI  - Chimerism in women with end stage renal diseases: Who's who?
AB  - Many sources of foreign or semi foreign cells, known as microchimerism (Mc), can
      be found in healthy individuals. We have recently shown in women with end stage
      renal disease (ESRD) that Mc frequencies and levels are exacerbated prior to
      kidney transplantation. Is Mc arising from pregnancy a protective factor for
      renal diseases explaining lower incidence in women? Is Mc helpful in slowing down
      disease progression? However, natural Mc is not the only actor as post blood
      transfusion Mc is also found at high levels in women with ESRD. The difficulty is
      therefore to distinguish the different types of Mc and this is made even more
      complicated when the recipient receives a potentially chimeric organ. What part
      does each source of chimerism play in disease and transplant fate, and can one
      decipher each role knowing that one chimerism may hide another?

PMID- 22854597
TI  - Facile formation of five-membered N-heterocyclic zirconacycloallenoids.
AB  - The reaction of eta(2)-iminozirconocene chloride complexes with
      trimethylsilylethynyl lithium leads to rapid C-C coupling at room temperature to
      yield the corresponding five-membered aza-zirconacycloallenoids. Such compounds
      were also obtained by trapping of in situ generated zirconocene with alkynyl
      imines.

PMID- 22854598
TI  - PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival
      PIDDosome signaling.
AB  - Biochemical evidence implicates the death-domain (DD) protein PIDD as a molecular
      switch capable of signaling cell survival or death in response to genotoxic
      stress. PIDD activity is determined by binding-partner selection at its DD:
      whereas recruitment of RIP1 triggers prosurvival NF-kappaB signaling, recruitment
      of RAIDD activates proapoptotic caspase-2 via PIDDosome formation. However, it
      remains unclear how interactor selection, and thus fate decision, is regulated at
      the PIDD platform. We show that the PIDDosome functions in the "Chk1-suppressed"
      apoptotic response to DNA damage, a conserved ATM/ATR-caspase-2 pathway
      antagonized by Chk1. In this pathway, ATM phosphorylates PIDD on Thr788 within
      the DD. This phosphorylation is necessary and sufficient for RAIDD binding and
      caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or
      activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM
      phosphorylation of the PIDD DD enables a binary switch through which cells elect
      to survive or die upon DNA injury.

PMID- 22854600
TI  - Comparison and phylogenetic analysis of the ISS gene in two predominant avian
      pathogenic E. coli serogroups isolated from avian colibacillosis in Iran.
AB  - The ISS (increased serum survival) gene and its protein product (ISS) of avian
      pathogenic Escherichia coli (APEC) are important characteristics of resistance to
      the complement system. The aims of this study were to clone, sequence and
      characterize sequence diversity of the ISS gene between two predominant
      serogroups in Iran and among those previously deposited in Genbank. The ISS gene
      of 309 bp from the APEC chi1390 strain was amplified by PCR, cloned and sequenced
      using pTZ57R/T vector. The ISS gene from the chi1390 strain has 100% identity
      among different serogroups of APEC in different geographical regions throughout
      the world. Phylogenetic analysis shows two different phylogenic groups among the
      different strains. Strong association of nucleotide sequences among different E.
      coli strains suggests that it may be a conserved gene and could be a suitable
      antigen to control and detect avian pathogenic E. coli, at least in our region.
      Currently, our group is working on the ISS protein as candidate vaccine in SPF
      poultry.

PMID- 22854599
TI  - Rem-GTPase regulates cardiac myocyte L-type calcium current.
AB  - RATIONALE: The L-type calcium channels (LTCC) are critical for maintaining Ca(2+)
      homeostasis. In heterologous expression studies, the RGK-class of Ras-related G
      proteins regulates LTCC function; however, the physiological relevance of RGK
      LTCC interactions is untested. OBJECTIVE: In this report we test the hypothesis
      that the RGK protein, Rem, modulates native Ca(2+) current (I(Ca,L)) via LTCC in
      murine cardiomyocytes. METHODS AND RESULTS: Rem knockout mice (Rem(-/-)) were
      engineered, and I(Ca,L) and Ca(2+) -handling properties were assessed. Rem(-/-)
      ventricular cardiomyocytes displayed increased I(Ca,L) density. I(Ca,L)
      activation was shifted positive on the voltage axis, and beta-adrenergic
      stimulation normalized this shift compared with wild-type I(Ca,L). Current
      kinetics, steady-state inactivation, and facilitation was unaffected by Rem(-/-)
      . Cell shortening was not significantly different. Increased I(Ca,L) density in
      the absence of frank phenotypic differences motivated us to explore putative
      compensatory mechanisms. Despite the larger I(Ca,L) density, Rem(-/-)
      cardiomyocyte Ca(2+) twitch transient amplitude was significantly less than that
      compared with wild type. Computer simulations and immunoblot analysis suggests
      that relative dephosphorylation of Rem(-/-) LTCC can account for the paradoxical
      decrease of Ca(2+) transients. CONCLUSIONS: This is the first demonstration that
      loss of an RGK protein influences I(Ca,L) in vivo in cardiac myocytes.

PMID- 22854601
TI  - Muscular arterial impedance in dogs with chronic degenerative mitral valve
      disease.
AB  - Systemic vascular impedance represents the retrograde strength of the blood flow
      to the left ventricle, thus it is one of the main compounds of afterload. Mitral
      regurgitation is markedly sensitive to afterload alterations. The purpose of this
      study was to evaluate muscular arterial impedance in dogs with chronic
      degenerative mitral valve disease (CDMVD) by use of duplex Doppler
      ultrasonography (DDU), since its technique there was not used before to determine
      impedance index in dogs with CDMVD. For this purpose, ten healthy dogs and ten
      dogs with CDMVD were used. Some parameters related to blood flow impedance in the
      common femoral artery were measured by DDU: pulsatility index (PI), resistance
      index (RI), high-resistance index (HRI), and acceleration velocity (AC) and
      deceleration velocity (DC) of the systolic peak. The results showed that RI and
      HRI were significantly higher in animals with CDMVD than in healthy animals.
      These findings showed that DDU provides quantitative data related to vascular
      impedance. Broader studies may therefore provide new aspects related to
      physiopathology and therapy in CDMVD patients.

PMID- 22854603
TI  - Current world literature.

PMID- 22854602
TI  - Consumption of sugar-sweetened beverages in relation to the metabolic syndrome
      among Iranian adults.
AB  - BACKGROUND: Few data are available linking intake of sugar-sweetened beverages
      (SSBs) with the metabolic syndrome. Furthermore, findings from these studies are
      inconsistent and most are from Western societies; no information is available in
      this regard from Middle Eastern populations. OBJECTIVE: This study was conducted
      to assess the relationship between SSB consumption and metabolic syndrome in an
      Iranian adult population. METHODS: In this cross-sectional study, data from 1,752
      people (782 men and 970 women) that were selected with the multistage cluster
      random sampling method from three counties of Isfahan, Najafabad and Arak were
      used. A validated food frequency questionnaire was used to assess participants'
      usual dietary intakes. Consumption of SSBs was calculated by summing up the
      consumption of 'soft drinks' and 'artificially sweetened fruit juices'. To
      categorize participants, we used three levels of SSB consumption: <1 time/week, 1
      3 times/week, and >3 times/week. Biochemical assessments were done after an
      overnight fasting. Metabolic syndrome was defined according to the guidelines of
      Adult Treatment Panel III. RESULTS: Subjects with high consumption of SSBs (>3
      times/week) were younger than those with low consumption (<1 time/week). Mean BMI
      was not significantly different across SSB categories. High consumption of SSBs
      was associated with greater intakes of energy and almost all food groups. We
      found a significant difference in serum triglyceride levels between men consuming
      SSBs 1-3 times/week and those consuming <1 time/week. However, after controlling
      for potential confounders, this association disappeared. In crude models, no
      significant associations were found between SSB intake and prevalence of the
      metabolic syndrome in either gender. After adjustment for potential confounders
      including BMI, we found that men in the top category of SSB intake were 17% more
      likely to have the metabolic syndrome (odds ratio (OR) 1.17; 95% confidence
      interval (95% CI) 0.56-2.46), while women in the highest category were 20% less
      likely to have the syndrome (OR 0.80; 95% CI 0.46-1.42) as compared with those in
      the bottom category. However, these associations were not significant in either
      men or women. CONCLUSION: Our results do not support the previous findings on the
      association between SSB consumption and metabolic syndrome. Prospective studies
      are needed to further explore for this association.

PMID- 22854605
TI  - Feasibility of double-blind clinical trials with oral diacetylmorphine: a
      randomized controlled phase II study in an inpatient setting.
AB  - The aim of this study was to evaluate the feasibility of conducting double-blind
      controlled randomized clinical trials using twice-a-day immediate-release oral
      diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the
      capacity of oral DAM to block opiate withdrawal and clinicians' ability to
      distinguish it from morphine and methadone. This was a randomized, phase II,
      double-blind, multicenter pilot study comparing immediate-release oral DAM, slow
      release oral morphine and oral methadone administered twice a day during 10 days.
      Forty-five heroin-dependent patients were randomly assigned to these three
      treatment groups in an inpatient regime. Patients were stabilized with a mean of
      350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow
      release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically
      significant differences were found between any studied medication in clinical
      outcome. Neither patients nor clinicians were able to identify the administered
      medication. This study shows the feasibility of double-blind clinical trials
      using b.i.d. immediate-release oral DAM allowing further phase III clinical
      trials in the process of introducing oral DAM as a medication for heroin
      dependent patients not responding to standard maintenance treatments.

PMID- 22854607
TI  - [Solutions for patients depend on whether we can bridge the divide between social
      and natural science research approaches in the area of mental health].

PMID- 22854606
TI  - Diabetes reduces beta-cell mitochondria and induces distinct morphological
      abnormalities, which are reproducible by high glucose in vitro with attendant
      dysfunction.
AB  - We investigated the impact of a diabetic state with hyperglycemia on morphometry
      of beta cell mitochondria and modifying influence of a K (+) -ATP channel opener
      and we related in vivo findings with glucose effects in vitro. For in vivo
      experiments islets from syngeneic rats were transplanted under the kidney capsule
      to neonatally streptozotocin-diabetic or non-diabetic recipients. Diabetic
      recipients received vehicle, or tifenazoxide (NN414), intragastrically for 9
      weeks. Non-diabetic rats received vehicle. Transplants were excised 7 d after
      cessation of treatment (wash-out) and prepared for electron microscopy.
      Morphological parameters were measured from approx. 25,000 mitochondria. Rat
      islets were cultured in vitro for 2-3 weeks at 27 or 11 (control) mmol/l glucose.
      Transplants to diabetic rats displayed decreased numbers of mitochondria (-31%, p
      < 0.05), increased mitochondrial volume and increased mitochondrial outer surface
      area, p < 0.001. Diabetes increased variability in mitochondrial size with
      frequent appearance of mega-mitochondria. Tifenazoxide partly normalized diabetes
      induced effects, and mega-mitochondria disappeared. Long-term culture of islets
      at 27 mmol/l glucose reproduced the in vivo morphological abnormalities. High
      glucose culture was also associated with reduced ATP and ADP contents, reduced
      oxygen consumption, reduced signaling by MitoTracker Red and reduction of
      mitochondrial proteins (complexes I-IV), OPA 1 and glucose-induced insulin
      release.   We conclude that (1) a long-term diabetic state leads to a reduced
      number of mitochondria and to distinct morphological abnormalities which are
      replicated by high glucose in vitro; (2) the morphological abnormalities are
      coupled to dysfunction; (3) K (+) -ATP channel openers may have potential to
      partly reverse glucose-induced effects.

PMID- 22854608
TI  - [The role of risk propensity in smokers and overweight people].
AB  - INTRODUCTION: The aim of this study is to investigate the nature of the link
      associating the risk propensity of smoking and overweight. For example, a person
      who is a smoker and obese does not have to be more prone to risk than another
      person who is obese and a non-smoker. MATERIAL AND METHODS: The data was taken
      from the German Questionnaire on Personality and Daily (Cross section for the
      period 2005). This questionnaire was selected because it collects individual data
      on the sociodemographic characteristic, behaviours, risk attitudes, lottery
      games, and health status. Our main contribution is to analyse the role of risk
      propensity taking into account smoking and overweight. RESULTS: Risk propensity
      encourages smoking, and to smoke and be overweight are positively associated.
      When the role of the unobserved characteristics are greater, the lower is the
      correlation between smoking and overweight. Although the risk propensity is an
      important determining factor of individual behaviour (smoking and overweight),
      its inclusion does not decrease the influence of personal circumstances and
      conditions. The need to define other measurements to be able to analyse the risk
      propensity of risk specific to risk behaviour is also highlighted. DISCUSSION: To
      reduce the number of smokers would require interventions in life styles. Given
      that overweight is an important determining factor in the decision to smoke, to
      encourage healthy behaviours, such as physical exercise or balanced diets, could
      improve the health status of the population on reducing obesity rates, and
      consequently the number of smokers.

PMID- 22854609
TI  - [Active and prodromal phase symptomatology of young-onset and late-onset paranoid
      schizophrenia].
AB  - INTRODUCTION: Young and late onset patients with paranoid schizophrenia were
      compared, regarding the initial prodromal and active phases of the disorder, in
      order to examine the influence of age of onset on the prodromal and active phase
      symptomatology of the disease. MATERIALS AND METHODS: We examined 88
      consecutively hospitalized patients with paranoid schizophrenia. Age cutoff
      points were set at <30 years of age for the young, and >=35 years of age for the
      late onset group. Diagnoses were made prospectively, using the Structured
      Clinical Interview for DSM-IV-Patient Edition for Axis I disorders (SCID-P). Type
      and severity of psychopathology in the active phase were assessed by applying the
      Structured Clinical Interview for Positive and Negative Syndrome Scale (PANSS).
      Patients were retrospectively examined regarding their initial prodromal symptoms
      by applying the Structured Clinical Interview for DSM-III-R Patient Edition and
      clinical interviewing for additional symptoms. Comparisons were performed by
      applying the two-tailed Wilcoxon rank-sum and the chi-square statistical tests.
      RESULTS: The young onset group was characterized by significantly more negative
      prodromal symptoms, and heavier negative symptomatology in the active phase, than
      the late onset group. Differences were more prominently shown in male patients.
      CONCLUSIONS: Older age of onset of paranoid schizophrenia appears to be related
      to a less severe form of the disease, characterized by less severity of negative
      symptomatology, already demonstrated in the prodromal phase of the disorder.

PMID- 22854610
TI  - [Psychopatological evaluation of traumatic brain injury patients with the
      Neuropsychiatric Inventory].
AB  - INTRODUCTION: The Neuropsychiatric Inventory (NPI) is a scale that assesses
      psychiatric symptoms in patients with neurological disorders, principally
      dementia. Despite its advantages, there are few published studies in traumatic
      brain injury (TBI) patients. With the NPI information we are going to describe
      the psychopatologic disorders in a group of TBI chronic patients and look the
      possible association with psychiatric history and outcome measures. METHOD: The
      NPI was applied to caregivers of 53 patients with severe TBI in chronic phase. We
      also collected functional and community integration scales. RESULTS: 92.5% of
      patients had some neuropsychiatric symptom, according to NPI. The most frequents
      were irritability/lability, apathy and depression/dysphoria. Those patients with
      drugs abuse history had more psychiatric symptoms. Presence of
      agitation/aggression, apathy and disinhibition were correlated with more
      disability. CONCLUSIONS: Psychiatric disorders are common between patients with
      TBI. The NPI is a scale that systematically assesses the behavioral and emotional
      disorders more common in these patients. Some of the symptoms negatively
      influence the degree of disability.

PMID- 22854611
TI  - [Gender-based violence against women the Aymara ethnic in northern Chile].
AB  - INTRODUCTION: We analyze the gender-based violence against women considering the
      Aymara ethnic ascendance as a casual factor. MATERIAL AND METHODS: We applied the
      spanish version of the Index of Spouse Abuse Scales (ISA) and Woman Abuse
      Screening Tool (WAST) on 400 women, which currently live in the region of Arica
      and Parinacota, Chile. RESULTS: The individuals show that non-physical violence
      is the predominant behavior in couples and higher rate of violence is present in
      women with Aymara ancestry than others. CONCLUSIONS: We conclude that social
      constructions of gender may be a risk factor in violence against women because of
      its influence in social inequalities and abuses of power against women.

PMID- 22854612
TI  - [Outpatient psychiatric care in the immigrant population of Segovia (2001-2008):
      descriptive study].
AB  - INTRODUCTION: Immigration is a phenomenon with a significant impact on mental
      health. The aims of this study were to describe health care characteristics, time
      trends, differences among Immigrant, and diagnoses associated with new outpatient
      psychiatric consultation Immigrant in Segovia. METHODS: A descriptive study of
      new consultations with sociodemographic, health care and clinical variables
      computerized records from the "Antonio Machado" Mental Health Center for 2001
      2002 and 2008 comparing immigrant and Spanish population. Population incidences
      were calculated by sex, geographic regions and countries of origin. By
      multivariate logistic regression assessed the relationship between ICD-10
      diagnoses and immigration. RESULTS: Immigrants had an average age 10 years
      younger than the Spanish. Incidence rate of new consultation was always higher in
      women, decreased in immigrants and increased in the Spanish between 2001 and
      2008. South Central Americans and Eastern Europeans had the highest and lowest
      rates of new visits, respectively. Bulgaria, Morocco, Romania and Poland were the
      countries most representative in 2008, with low incidences. Neurotic and
      somatoform disorders were the most common regardless of the origin of the
      patient. Psychotic and personality disorders were positively associated with
      immigration in the multivariate analysis. CONCLUSIONS: The attention of mental
      health immigrants in Segovia is characterized by young age, lower incidence of
      new queries with important variations between regions, and diagnostic association
      with processes more severe, which may reflect underdiagnosis and underutilization
      phenomena.

PMID- 22854613
TI  - [Variables associated with disability in elderly bipolar patients on ambulatory
      treatment].
AB  - INTRODUCTION: Studies on adult bipolar patients have demonstrated a disability
      associated with the bipolar disorder, even in euthymic patients, but there is a
      lack of data in the elderly population. MATERIAL AND METHOD: A cross-sectional,
      multicentre study on a consecutive sample of ambulatory bipolar patients (DSM-IV
      TR criteria), aged 65 years or over. Retrospective and cross-sectional
      sociodemographic and clinical data were collected, as well as the Clinical Global
      Impression for Bipolar Modified scale (CGI-BP-M) and the level of disability
      using the World Health Organisation Disability Assessment Schedule (WHO/DAS). The
      disability was assessed globally and by areas. The presence of a moderate to
      maximum disability compared to a mild to no disability was considered a dependent
      variable. RESULTS: A moderate to maximum global disability was present in 43.6%
      of the sample. By areas, occupational functioning was the area most frequently
      affected, and personal care the least affected. The only variables which were
      associated with disability were the presence of medical comorbidity (P = .01),
      increased age (P = .005) global clinical severity (P = .0001) and in the
      depressive pole (P = .03). There was no relationship between clinical subtype,
      duration of the disease, number of previous episodes, number of hospitalisations,
      or other clinical variables and the degree of disability. CONCLUSIONS: These data
      underline the need to establish specific therapeutic strategies in the approach
      to depressive symptoms and medical comorbidity, with the aim of minimising the
      disability in elderly bipolar patients. Given the lack of current data, new
      studies are needed with larger samples and control groups.

PMID- 22854614
TI  - [Burden of care in Aymara caregivers of patients with schizophrenia].
AB  - INTRODUCTION: The introduction of anti-psychotic medication and the de
      institutionalization have placed on the hands of their relatives the
      responsibility for their informal care. Many times, this role carries a high
      level of burden for all family members. There exist a few studies that approach
      this subject matter in groups of ethnic minority. The aim of this research was to
      describe the levels of burden in Aymaras caregivers (aborigines who are located
      on the highlands of Northen Chile) from Schizophrenia patients. MATERIAL AND
      METHODS: The sample corresponds to 45 caregivers of patients with schizophrenia
      that receive treatment at the Mental Health Services in the city of Arica, Chile.
      RESULTS: [corrected] Zarit Burden Scale classifies all Aymara relatives in the
      category of "Intense Burden", unlike not Aymara relatives, which classified as
      "Low Burden". Significant differences are observed in the subscale of
      incompetence where the Aymara Cargivers perceive not to feel able of taking care
      of the patient with the available resources. CONCLUSIONS: It is concludes that
      belonging to this ethnic minority would increase the psychopathological risk that
      caregivers of psychiatric patients experience.

PMID- 22854615
TI  - [Eating disorders: Considerations on nosology, etiology and treatment in the XXI
      century].
AB  - Amazing advances have been made in medical sciences since the first international
      conference on eating disorders (ED) was held in the 1970s, and there have been
      remarkable changes in the field of ED itself. Back then, virtually all that was
      talked about was anorexia nervosa; clinicians and researchers were mainly
      concerned about the possible hypothalamic and endocrine factors that seemed to be
      involved and there had been no epidemiological studies or controlled trials with
      psychiatric drugs or psychotherapy. Although the picture today is quite
      different, there are still significant gaps which even affect the classification
      of these disorders, as well as their neurobiological bases and both the
      pharmacological and psychological treatments which should be used. This paper
      gives a brief summary of these gaps and discusses the need to find endophenotypes
      which may help in categorising and directing research into these disorders.
      Mention is made of possible contributions from other fields for the benefit of
      greater progress in understanding eating disorders. Specific reference is made to
      the addictive model, out of which neuropsychology and animal models may provide
      data transferable to our area of expertise. Lastly, the current state of ED
      treatment is discussed with pointers as to from what perspective it would be most
      useful to seek improvements.

PMID- 22854616
TI  - [Primary hypersexuality: nosological status, pathogenesis, and treatment].

PMID- 22854617
TI  - Concentrations of organophosphate esters and brominated flame retardants in
      German indoor dust samples.
AB  - While it is known that the ingestion of indoor dust contributes substantially to
      human exposure to the recently restricted polybrominated diphenyl ethers (PBDEs),
      the situation for one class of potential replacements, i.e. organophosphate
      esters (OPEs), used in a variety of applications including as flame retardants
      has yet to be fully characterised. In this study, surface dust from twelve
      different cars from various locations throughout Germany were analysed for eight
      OPEs, decabromodiphenyl ethane (DBDPE), and eight PBDEs. In five cars, tris-(1,3
      dichloro-2-propyl) phosphate (TDCPP) was the dominant compound with
      concentrations up to 620 MUg g(-1) dust. High concentrations of tri-cresyl
      phosphate (TCP) (up to 150 MUg g(-1)) were also detected in two samples of car
      dust. Dust from ten offices in the same building in Ludwigsburg, Germany was also
      analysed. In these samples, tri (2-butoxyethyl) phosphate (TBEP) predominated
      with an average concentration of 7.0 MUg g(-1) dust, followed by tris (1-chloro-2
      propyl) phosphate (TCPP) at 3.0 MUg g(-1) and triphenyl phosphate (TPhP) at 2.5
      MUg g(-1) dust. Although caution must be exercised given the relatively small
      database reported here; this study provides evidence that cars and offices from
      Germany are significantly more contaminated with OPEs than PBDEs. Average
      concentrations of SigmaOPEs were ten times higher in car than in office dust.
      This is the first study to provide data on a wide range of OPE concentrations in
      German indoor dust samples.

PMID- 22854619
TI  - [Prognostic factors in severe traumatic brain injury].
AB  - OBJECTIVE: To describe the factors associated to mortality of patients with
      severe traumatic brain injury (TBI). DESIGN: A retrospective observational study
      was made of patients with severe TBI covering the period between 1 January 2007
      and 31 December 2010. SETTING: Virgen de la Vega Hospital, Salamanca (Spain).
      PATIENTS: All patients hospitalized during the consecutive study period. MAIN
      VARIABLES OF INTEREST: The dependent variable has been the death rate, while the
      independent variables were divided into two groups: epidemiological and clinical.
      RESULTS: The mean patient age was the 50.84 years; 75.5% were males. The average
      score on the Glasgow Coma Scale (GCS) was 5.09, and the average Injury Severity
      Score (ISS) was 30.8. Higher mortality was observed in older patients with a
      higher ISS score. A total of 68.1% of the patients in which intracranial pressure
      (ICP) was monitored showed intracranial hypertension (ICH). The mortality rate in
      patients with severe TBI was 36.8%, and was associated mainly to a lower GCS
      score, the existence of hyperglycemia, coagulopathy, hypoxemia, the presence of
      mydriasis and shock. The independent mortality indicators in patients with severe
      TBI were the existence of mydriasis (OR: 32.75), the GCS score (OR: 2.65) and
      hyperglycemia (OR: 6.08). CONCLUSIONS: The existence of mydriasis, the GCS score
      and hyperglycemia should be taken into account as prognostic factors in TBI
      patients.

PMID- 22854620
TI  - Advances in immunosuppression after lung transplantation.
AB  - Immunosuppression in transplantation has experienced changes in recent years as a
      result of the introduction of new drugs that act upon the different pathways of
      the host immune response with the purpose of securing more individualized immune
      suppression, with fewer side effects. Although following in the steps of other
      solid organ transplant modalities, lung transplantation, because of its special
      characteristics, has not yielded similar middle- and long-term results. Improved
      understanding of the underlying rejection mechanisms, the pharmacodynamic control
      of drugs, new administration routes designed to reduce the side effects, and new
      drug substances or immune modulating processes will all contribute to improve the
      expectations associated to lung transplantation in the near future.

PMID- 22854618
TI  - Community-acquired Legionella Pneumonia in the intensive care unit: Impact on
      survival of combined antibiotic therapy.
AB  - OBJECTIVES: To compare intensive care unit (ICU) mortality in patients with
      severe community-acquired pneumonia (SCAP) caused by Legionella pneumophila
      receiving combined therapy or monotherapy. METHODS: A prospective multicenter
      study was made, including all patients with sporadic, community-acquired
      Legionnaires' disease (LD) admitted to the ICU. Admission data and information on
      the course of the disease were recorded. Antibiotic prescriptions were left to
      the discretion of the attending physician and were not standardized. RESULTS:
      Twenty-five cases of SCAP due to L. pneumophila were included, and 7 patients
      (28%) out of 25 died after a median of 7 days of mechanical ventilation. Fifteen
      patients (60%) presented shock. Levofloxacin and clarithromycin were the
      antibiotics most commonly used in monotherapy, while the most frequent
      combination was rifampicin plus clarithromycin. Patients subjected to combination
      therapy presented a lower mortality rate versus patients subjected to monotherapy
      (odds ratio for death [OR] 0.15; 95%CI 0.02-1.04; p=0.08). In patients with
      shock, this association was stronger and proved statistically significant (OR for
      death 0.06; 95%CI 0.004-0.86; p=0.04). CONCLUSIONS: Combined antibiotic therapy
      decreases mortality in patients with SCAP and shock caused by L. pneumophila.

PMID- 22854621
TI  - Reflections on the field of photoimmunology.
AB  - Photoimmunology evolved from experiments carried out in the 1970s on the
      immunology of cancer. In studying the antigenic properties of skin cancers
      induced in mice by UV radiation, I found that most of these tumors failed to grow
      when transplanted into normal, syngeneic mice but grew progressively in
      immunosuppressed mice. Thus, these UV-induced skin cancers were highly antigenic.
      The critical question was, how can these antigenic skin cancers escape immune
      rejection in their primary host? The answer was that exposing their skin to UV
      radiation prevented mice from triggering an immune response against their tumors.
      The failure to reject these tumors was owing to the development of UV tumor
      specific regulatory T cells during the course of irradiation. In unraveling the
      mechanisms of this effect of UV, much has been learned about the immunology of
      the skin, including the function of Langerhans cells, the migration of immune
      cells in skin, the role of antigen-presenting cells in directing the immune
      response, and the role of keratinocytes as producers of immunological mediators.
      Thus, photoimmunology helped demonstrate that skin is an important immunological
      organ, and that the immune system can be influenced by the external environment
      via the skin.

PMID- 22854622
TI  - 1,25-dihydroxyvitamin D exerts similar immunosuppressive effects as UVR but is
      dispensable for local UVR-induced immunosuppression.
AB  - Low-dose UV radiation (UVR) inhibits the induction of contact hypersensitivity
      and induces regulatory T cells (Tregs), which because of their antigen
      specificity harbor therapeutic potential. Topical application of 1alpha,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is known to induce Tregs as well, which
      implies that 1,25(OH)(2)D(3) might be involved in UVR-induced immunosuppression.
      It was the aim of this study to clarify this issue, to further characterize
      1,25(OH)(2)D(3)-induced Tregs and to determine whether they differ from UVR
      induced Tregs. Our data demonstrate that 1,25(OH)(2)D(3)-induced Tregs act in an
      antigen-specific manner and belong to the Foxp3-expressing subtype of Tregs as
      demonstrated by diphtheria toxin (DT)-mediated depletion of Foxp3(+) Tregs in
      DEREG (depletion of Tregs) mice. Using Langerin-DTR (DT receptor) knock-in mice,
      it was shown that Langerhans cells (LCs) are required for the induction of Tregs
      by 1,25(OH)(2)D(3), as depletion of LCs but not Langerin(+) dermal dendritic
      cells abrogated the induction of Tregs. Taken together, 1,25(OH)(2)D(3) affects
      the immune system in a similar manner as UVR, probably using the same pathways.
      However, vitamin D receptor knockout mice were equally susceptible to UVR-induced
      immunosupppression as wild-type controls. This indicates that 1,25(OH)(2)D(3)
      exerts similar immunosuppressive effects as UVR but is dispensable for local UVR
      induced immunosuppression.

PMID- 22854623
TI  - Epidermolysis bullosa simplex ogna revisited.

PMID- 22854624
TI  - Consumption of cigarettes and combustible tobacco--United States, 2000-2011.
AB  - Smoking cigarettes and other combustible tobacco products causes adverse health
      outcomes, particularly cancer and cardiovascular and pulmonary diseases. A
      priority of the U.S. Department of Health and Human Services is to develop
      innovative, rapid-response surveillance systems for assessing changes in tobacco
      use and related health outcomes. The two standard approaches for measuring
      smoking rates and behaviors are 1) surveying a representative sample of the
      public and asking questions about personal smoking behaviors and 2) estimating
      consumption based on tobacco excise tax data. Whereas CDC regularly publishes
      findings on national and state-specific smoking rates from public surveys, CDC
      has not reported consumption estimates. The U.S. Department of Agriculture
      (USDA), which previously provided such estimates, stopped reporting on
      consumption in 2007. To estimate consumption for the period 2000-2011, CDC
      examined excise tax data from the U.S. Department of Treasury's Alcohol and
      Tobacco Tax and Trade Bureau (TTB); consumption estimates were calculated for
      cigarettes, roll-your-own tobacco, pipe tobacco, and small and large cigars. From
      2000 to 2011, total consumption of all combustible tobacco decreased from 450.7
      billion cigarette equivalents to 326.6, a 27.5% decrease; per capita consumption
      of all combustible tobacco products declined from 2,148 to 1,374, a 36.0%
      decrease. However, while consumption of cigarettes decreased 32.8% from 2000 to
      2011, consumption of loose tobacco and cigars increased 123.1% over the same
      period. As a result, the percentage of total combustible tobacco consumption
      composed of loose tobacco and cigars increased from 3.4% in 2000 to 10.4% in
      2011. The data suggest that certain smokers have switched from cigarettes to
      other combustible tobacco products, most notably since a 2009 increase in the
      federal tobacco excise tax that created tax disparities between product types.

PMID- 22854625
TI  - Public health interventions involving travelers with tuberculosis--U.S. ports of
      entry, 2007-2012.
AB  - Every day, approximately 950,000 international travelers arrive in the United
      States. The Secretary of the U.S. Department of Health and Human Services is
      authorized to prevent the introduction, transmission, and spread of communicable
      diseases by travelers into and within the United States. The Secretary, through
      the CDC director, delegates this authority to CDC's Division of Global Migration
      and Quarantine (DGMQ). Of the communicable diseases for which federal quarantine
      and isolation are authorized by executive orders of the president, infectious
      tuberculosis (TB) is encountered most commonly by DGMQ's network of quarantine
      stations at major U.S. ports of entry. Although legal immigrants and refugees
      undergo U.S. State Department-mandated TB screening overseas, CDC receives
      approximately 125 reports each year of arriving travelers with active TB,
      including foreign visitors, foreign students, and temporary workers (CDC,
      unpublished data, 2012). This report describes two cases that illustrate the TB
      control and prevention activities of quarantine stations.  Such activities,
      including issuing federal isolation orders, restricting travel, arranging safe
      transport for patients across state lines, and conducting airline contact
      investigations, support CDC's mission to limit the spread of infectious disease
      from travelers.

PMID- 22854626
TI  - Infant lead poisoning associated with use of tiro, an eye cosmetic from Nigeria-
      Boston, Massachusetts, 2011.
AB  - Lead is highly toxic and can damage the brain, kidneys, bone marrow, and other
      body systems; high levels can cause convulsions, coma, and death. Young children
      are especially susceptible to lead exposures because of their floor-hand-mouth
      activity, greater gut absorption, and developing central nervous systems. In June
      2011, a male infant aged 6 months of Nigerian descent was referred to the
      Pediatric Environmental Health Specialty Unit (PEHSU) at Boston Children's
      Hospital because of an elevated blood lead level (BLL). An investigation found no
      lead exposure except for "tiro," a Nigerian cosmetic that also is used as a folk
      remedy to promote visual development. The tiro applied to the infant's eyelids
      contained 82.6% lead. Products similar to tiro, such as "surma" and "kajal" in
      Asia and kohl in the Middle East, also might contain lead. This case adds to the
      medical literature documenting nonpaint lead sources as causes of elevated BLLs
      in children and highlights persons of certain immigrant populations as a risk
      group. Educational efforts are needed to inform immigrants from Africa, Asia, and
      the Middle East that tiro and similar products can cause lead poisoning in
      children. Health-care providers and public health workers should ask about eye
      cosmetics and folk remedies when seeking a source of exposure in children with
      elevated BLLs from certain immigrant populations.

PMID- 22854628
TI  - The nurse thing.

PMID- 22854627
TI  - Inhibition of Ca(2+) entry and suicidal erythrocyte death by naringin.
AB  - Naringin is a dietary flavonoid from citrus fruits with antioxidant and
      antiapoptotic activity. Similar to apoptosis of nucleated cells, suicidal death
      of erythrocytes or eryptosis is paralleled by cell shrinkage and cell membrane
      scrambling with phosphatidylserine exposure at the erythrocyte surface. Eryptosis
      is triggered by increased cytosolic Ca(2+) activity, e.g. following energy
      depletion or oxidative stress. The present study thus explored whether naringin
      interferes with eryptosis. To this end, the cytosolic Ca(2+) concentration was
      estimated from Fluo3 fluorescence, phosphatidylserine exposure from annexin-V
      binding and cell volume from forward scatter in FACS analysis. As a result,
      energy depletion (48 h glucose removal) and oxidative stress (30 min exposure to
      0.3 mM tert-butylhydroperoxide) increased Fluo-3 fluorescence, decreased the
      erythrocyte forward scatter and enhanced the percentage of annexin-V-binding
      erythrocytes. Naringin (up to 40 uM) did not significantly modify Fluo-3
      fluorescence, erythrocyte forward scatter or annexin-V-binding in the presence of
      glucose and absence of oxidative stress. Naringin, however, significantly blunted
      the effect of glucose depletion and oxidative stress on Fluo-3 fluorescence,
      erythrocyte forward scatter or annexin-V-binding. In conclusion, naringin blunts
      the increase of cytosolic Ca(2+) concentration, the shrinkage, the cell membrane
      scrambling and thus the suicidal death of erythrocytes following energy depletion
      or oxidative stress.

PMID- 22854629
TI  - [Control of bleeding in the military environment].
AB  - One of the basics of military medicine is the control of haemorrhagic shock.
      Haemorrhage is the first cause of preventable death in combat, with the adequate
      control of bleeding being considered as fundamental to estimate the survival of
      the combatant as well as therapeutic support aimed at minimising blood loss being
      a challenge within military health logistics. The aim of this work is to review
      the medical and logistics advances in the treatment of bleeding in the military
      environment and combat during the latest conflicts, and to describe what is the
      current contribution of the Spanish Armed Forces and to profile future lines of
      investigation.

PMID- 22854630
TI  - [Laryngoscopy and tracheal intubation with Airtraq in a pediatric patient with
      branchio-oto-renal syndrome].

PMID- 22854631
TI  - Prevalence of problem drug use and injecting drug use in Luxembourg: a
      longitudinal and methodological perspective.
AB  - BACKGROUND: To estimate the prevalence of problem drug use (PDU) and injecting
      drug use (IDU) in Luxembourg and analyze trends between 1997 and 2009. To assess
      the feasibility of prevalence estimations based on drug use surveillance systems.
      METHODS: Serial multi-method PDU/IDU prevalence estimations based upon capture
      recapture, Poisson regression, multiplier and back-calculation methods.
      Comparative analysis of methods and assessment of their robustness to variations
      of external factors. RESULTS: National PDU and IDU prevalence rates were
      estimated at 6.16/1,000 (95% CI 4.62/1,000 to 7.81/1,000) and 5.68/1,000 (95% CI
      4.53/1,000 to 6.85/1,000) inhabitants aged 15-64 years, respectively. Absolute
      prevalence and prevalence rates of PDU increased between 1997 and 2000 and
      declined from 2003 onwards, whereas IDU absolute prevalence and prevalence rates
      witnessed an increasing trend between 1997 and 2007. CONCLUSIONS: Drug use
      surveillance systems can be valuable instruments for the estimation and trend
      analysis of drug misuse prevalence given multiple methods are applied that rely
      on serial and representative data from different sources and different settings,
      control multiple counts and build upon standardized and sustained data collection
      routines. The described institutional contact indicator revealed to be a useful
      tool in the context of PDU/IDU prevalence estimations and thus contributes to
      enhancing evidence-based drug policy planning.

PMID- 22854632
TI  - Gastrobronchial fistula as a complication of bariatric surgery: a series of 6
      cases.
AB  - OBJECTIVE: To present a multicenter series of 6 patients who developed
      gastrobronchial fistula (GBF). GBF is a rare subtype of gastric leaks following
      bariatric surgery, which is the mainstay of treatment for the obesity pandemic.
      METHODS: We retrospectively identified 6 patients with GBF (out of 2,308 cases
      performed: 0.2%). One patient had undergone Roux-en-Y gastric bypass, and 5 had a
      sleeve gastrectomy. Demographics, previous surgeries, clinical presentation,
      timing of fistula diagnosis, diagnostic and treatment measures employed, and
      outcome were collected. RESULTS: Four patients were female, the average age and
      BMI were 42 years and 42.5 kg/m2, respectively. Three patients had previous
      surgeries (Nissen fundoplication, adjustable gastric banding, and vertical banded
      gastroplasty). Median time to fistula diagnosis was 40 days (range 15-90 days).
      Clinical presentation included chronic cough, hemoptysis, dyspnea and fever as
      well as persistent left pleural effusion or pneumonia. Diagnosis was confirmed by
      computed tomography in all cases. Two patients were treated nonoperatively, while
      4 eventually required surgery for resolution. Left lower lobectomy was necessary
      in 3 of 4 cases. Concomitant procedures were total gastrectomy in 2 cases and
      conversion of a sleeve to a gastric bypass in 1 case. Resolution occurred 30 days
      to 2 years after initial surgery. No mortalities were encountered. CONCLUSIONS:
      GBF is a rare but devastating complication following bariatric surgery. It may
      develop as a late complication of a chronic upper gastric leak. Surgery is
      curative although nonoperative management may be warranted in selected cases.

PMID- 22854633
TI  - A simulator study of the effects of singing on driving performance.
AB  - This study aimed to investigate how singing while driving affects driver
      performance. Twenty-one participants completed three trials of a simulated drive
      concurrently while performing a peripheral detection task (PDT); each trial was
      conducted either without music, with participants listening to music, or with
      participants singing along to music. It was hypothesised that driving performance
      and PDT response times would be impaired, and that driver subjective workload
      ratings would be higher, when participants were singing to music compared to when
      there was no music or when participants were listening to music. As expected,
      singing while driving was rated as more mentally demanding, and resulted in
      slower and more variable speeds, than driving without music. Listening to music
      was associated with the slowest speeds overall, and fewer lane excursions than
      the no music condition. Interestingly, both music conditions were associated with
      slower speed-adjusted PDT response times and significantly less deviation within
      the lane than was driving without music. Collectively, results suggest that
      singing while driving alters driving performance and impairs hazard perception
      while at the same time increasing subjective mental workload. However, singing
      while driving does not appear to affect driving performance more than simply
      listening to music. Further, drivers' efforts to compensate for the increased
      mental workload associated with singing and listening to music by slowing down
      appear to be insufficient, as evidenced by relative increases in PDT response
      times in these two conditions compared to baseline.

PMID- 22854635
TI  - [Performance of the VIDAS automated immunoassay for the determination of Epstein
      Barr virus serological status].
AB  - Enzyme linked fluorescent assays (VIDAS EBV VCA IgM, VIDAS EBV VCA/EA IgG and
      VIDAS EBV EBNA IgG (Biomerieux, France) were evaluated to determine markers for
      infection of Epstein Barr virus, as well as to establish antibody profiles,
      compared with immunofluorescence assays as reference. The assays evaluated showed
      good values for sensitivity, specificity and agreement, making them useful for
      their application in clinical laboratories.

PMID- 22854634
TI  - Soft microenvironments promote the early neurogenic differentiation but not self
      renewal of human pluripotent stem cells.
AB  - Human pluripotent stem cells (hPSCs) are of great interest in biology and
      medicine due to their ability to self-renew and differentiate into any adult or
      fetal cell type. Important efforts have identified biochemical factors, signaling
      pathways, and transcriptional networks that regulate hPSC biology. However,
      recent work investigating the effect of biophysical cues on mammalian cells and
      adult stem cells suggests that the mechanical properties of the microenvironment,
      such as stiffness, may also regulate hPSC behavior. While several studies have
      explored this mechanoregulation in mouse embryonic stem cells (mESCs), it has
      been challenging to extrapolate these findings and thereby explore their
      biomedical implications in hPSCs. For example, it remains unclear whether hPSCs
      can be driven down a given tissue lineage by providing tissue-mimetic stiffness
      cues. Here we address this open question by investigating the regulation of hPSC
      neurogenesis by microenvironmental stiffness. We find that increasing
      extracellular matrix (ECM) stiffness in vitro increases hPSC cell and colony
      spread area but does not alter self-renewal, in contrast to past studies with
      mESCs. However, softer ECMs with stiffnesses similar to that of neural tissue
      promote the generation of early neural ectoderm. This mechanosensitive increase
      in neural ectoderm requires only a short 5-day soft stiffness "pulse", which
      translates into downstream increases in both total neurons as well as
      therapeutically relevant dopaminergic neurons. These findings further highlight
      important differences between mESCs and hPSCs and have implications for both the
      design of future biomaterials as well as our understanding of early embryonic
      development.

PMID- 22854636
TI  - Cardiac events in hypertensive patients with renal artery stenosis treated with
      renal angioplasty or drug therapy: meta-analysis of randomized trials.
AB  - BACKGROUND: Cardiac outcome in patients with atherosclerotic renal artery
      stenosis (ARAS) undergoing percutaneous transluminal renal angioplasty (PTRA) or
      medical therapy is not yet completely clear. The aim of this study was to perform
      a meta-analysis of randomized controlled trials to compare the effect of PTRA and
      medical therapy on nonfatal myocardial infarction in patients with ARAS. METHODS:
      We searched for articles reporting cardiovascular outcome, including nonfatal
      myocardial infarction, in patients with renal artery stenosis randomized to PTRA
      with/without stenting or medical therapy. RESULTS: Five studies were identified.
      The pooled population consisted of 1,159 subjects who experienced 56 nonfatal
      myocardial infarctions. When compared with medical therapy, the overall relative
      risk (RR) was 0.85 (95% confidence interval (CI) 0.51-1.42), P = 0.55, for PTRA.
      There was no significant difference between PTRA and medical therapy according to
      procedural characteristics (with/without stent placement), mean serum creatinine
      at follow-up (higher or lower than 2.0 mg/dl), and maximum follow-up length (> or
      <2 years). CONCLUSIONS: In patients with ARAS and hypertension, there is a lack
      of evidence supporting the superiority of PTRA over medical therapy in prevention
      of nonfatal myocardial infarction. Awaiting for results of ongoing trials, our
      data and previous data suggest that PTRA and drug therapy have a similar impact
      on cardiovascular risk reduction in patients with renal artery stenosis and
      hypertension.

PMID- 22854637
TI  - Blood pressure control in Italian essential hypertensives treated by general
      practitioners.
AB  - BACKGROUND: Adequate control of blood pressure (BP) is limited worldwide. This
      has serious consequences for public health because in hypertensive patients,
      uncontrolled BP is associated with a higher incidence of cardiovascular events,
      particularly stroke. The aim of this study was to investigate BP control in a
      cohort of treated patients with diagnosed hypertension, who were under general
      practitioner care in Italy. METHODS: Data were collected by 2,643 physicians on
      8,572 individual Italian patients. Office BP was measured 5 min after seating
      each patient and then 3-5 min later. For each patient, data such as medical
      history of patients, physical examination data, antihypertensive drug usage, and
      self-BP measurement frequency were obtained. RESULTS: Male prevalence was 48.4%,
      and mean age was 64.3 +/- 10.5 years. Based on the second measurement, BP control
      (<140/90 mm Hg) was observed in 33.5% of all patients (34.2% in men and 33.4% in
      women). BP control was much lower for systolic BP than for diastolic BP (35.9 vs.
      61.3%, P < 0.0001); moreover, BP control was much more common in patients who
      were engaged in self-BP measurement (61.2 vs. 38.8%, P < 0.0001). A stricter BP
      control recommended by the guidelines of the European Society of Hypertension
      (ESH) and European Society of Cardiology (ESC) (<130/80 mm Hg) was observed in
      only 5.5% of diabetic patients. CONCLUSIONS: In treated Italian hypertensives
      effective BP control remains uncommon largely due to the failure to appropriately
      reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines
      for diabetic patients are achieved only by a small fraction of hypertensive
      diabetic population.

PMID- 22854638
TI  - Association of insomnia and short sleep duration with atherosclerosis risk in the
      elderly.
AB  - BACKGROUND: Short sleep duration is associated with an increased risk of
      cardiovascular disease and all-cause mortality, although a relationship with
      atherosclerosis in the elderly remains unclear. METHODS: Eighty-six volunteers
      aged >=65 years (mean, 73.6 +/- 4.9 years) were evaluated for insomnia. Total
      sleep time (TST) and sleep efficiency were measured by actigraphy. Subjective
      symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI).
      Atherosclerosis was evaluated using ultrasonographic measurements of carotid
      intima-media thickness (IMT). RESULTS: IMT was significantly greater and sleep
      efficiency was significantly lower in subjects with TST <=5 h than those with TST
      >7 h (1.3 +/- 0.5 vs. 0.9 +/- 0.3 mm; P = 0.009; 91.0 +/- 6.0 vs. 81.6 +/- 11.3%,
      P = 0.03, respectively). IMT was also significantly greater in the insomnia group
      than the noninsomnia group (1.3 +/- 0.5 vs. 1.1 +/- 0.4 mm; P = 0.03). IMT was
      significantly correlated with systolic blood pressure (SBP), diastolic blood
      pressure (DBP), and TST (SBP: r = 0.49, P < 0.0001; DBP: r = 0.33, P = 0.0021;
      TST: r = -0.28, P = 0.010). Multiple regression analysis revealed that SBP, TST,
      and the PSQI were significant contributing factors for increased IMT (SBP:
      coefficient beta = 0.56, P = 0.0001; TST: coefficient beta = -0.32, P = 0.005;
      PSQI: coefficient beta = 0.22, P = 0.05). CONCLUSIONS: High blood pressure, short
      sleep duration (<=5 h), poor sleep, and insomnia were associated with
      atherosclerosis risk leading to cardiovascular disease in the elderly.

PMID- 22854639
TI  - Effect of cholecalciferol supplementation during winter months in patients with
      hypertension: a randomized, placebo-controlled trial.
AB  - BACKGROUND: Low 25-hydroxy-vitamin D (25(OH)D) levels are inversely related to
      blood pressure (BP) and have been associated with incident hypertension. In
      people living at northern latitudes diminished cholecalciferol synthesis in the
      winter increases the risk of vitamin D deficiency. We wanted to test the
      hypothesis that daily cholecalciferol supplementation in the winter lowers BP in
      patients with hypertension. METHODS: We investigated the effect of 75 ug (3,000
      IU) cholecalciferol per day in a randomized, placebo-controlled, double-blind
      study in 130 hypertensive patients residing in Denmark (56o N). Ambulatory BP (24
      h BP) and arterial stiffness were measured before and after 20 weeks of
      treatment, that took place between October and March. RESULTS: A total of 112
      patients (mean age 61 +/- 10) with a baseline p-25(OH)D of 23 +/- 10 ng/ml
      completed the study. Compared with placebo, a nonsignificant 3/1 mm Hg (P =
      0.26/0.18) reduction was found in 24-h BP. In patients with vitamin D
      insufficiency (<32 ng/ml) at baseline (n = 92), 24-h BP decreased by 4/3 mm Hg (P
      = 0.05/0.01). Central BP (CBP) estimated by applanation tonometry and calibrated
      with a standardized office BP was reduced by 7/2 mm Hg (P = 0.007/0.15) vs.
      placebo. No differences in carotid-femoral pulse wave velocity (PWV) or central
      augmentation index (AIx) were found between treatment arms. CONCLUSIONS:
      Cholecalciferol supplementation, by a dose that effectively increased vitamin D
      levels, did not reduce 24-h BP, although central systolic BP decreased
      significantly. In a post-hoc subgroup analysis of 92 subjects with baseline p
      25(OH)D levels <32 ng/ml, significant decreases in 24-h systolic and diastolic BP
      occurred during cholecalciferol supplementation.

PMID- 22854640
TI  - Paraoxonase 1 (PON1) C/T-108 association with longitudinal mean arterial blood
      pressure.
AB  - BACKGROUND: Blood pressure is a complex quantitative trait with a strong genetic
      component. In this study, we leveraged the Veterans Affairs electronic medical
      record system to explore the relationship between Paraoxonase 1 (PON1)-108 C/T
      (rs705379) and mean arterial blood pressure (MAP). METHODS: Outpatient blood
      pressure data over an approximate 8-year period was collected from the Veterans
      Affairs Hypertensive Cohort (N = 1,302). Association between genotype and
      longitudinal MAP was further explored using a random effects model controlling
      for age, ancestry, renal function, and other determinants of blood pressure. To
      control for population stratification, principal component groupings based on
      ancestry informative markers in this dataset were included as covariates (in
      addition to self-identified ancestry). Data from the African American Study of
      Kidney Disease and Hypertension (AASK, N = 857) was used to confirm significant
      findings in an independent cohort. RESULTS: There was a significant interaction
      between PON1-108 C/T genotype and follow-up age group. At a younger age (<50
      years), there was an estimated 2.53 mm Hg (95% confidence interval: 1.06, 4.00)
      increase in MAP with each additional C-allele. At the older age groups, there
      were no significant associations between PON1-108 C/T genotype and MAP. Using
      data from the AASK trial, the C-allele at PON1-108 C/T was significantly
      associated with a higher MAP (P = 0.005) but only among younger participants (<54
      years). CONCLUSIONS: The PON1-108 polymorphism may be associated with MAP in an
      age-dependent manner.

PMID- 22854641
TI  - Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid
      nephropathy.
AB  - Experimental aristolochic acid nephropathy is characterized by early
      tubulointerstitial injury followed by fibrosis, reproducing chronic lesions seen
      in humans. In vitro, probenecid inhibits aristolochic acid entry through organic
      anion transporters, reduces specific aristolochic acid-DNA adduct formation, and
      preserves cellular viability. To test this in vivo, we used a mouse model of
      aristolochic acid nephropathy displaying severe tubulointerstitial injuries
      consisting of proximal tubular epithelial cell necrosis associated to transient
      acute kidney injury followed by mononuclear cell infiltration, tubular atrophy,
      and interstitial fibrosis. Treatment with probenecid prevented increased plasma
      creatinine and tubulointerstitial injuries, and reduced both the extent and the
      severity of ultrastructural lesions induced by aristolochic acid, such as the
      loss of brush border, mitochondrial edema, and the disappearance of mitochondrial
      crests. Further, the number of proliferating cell nuclear antigen-positive cells
      and total aristolochic acid-DNA adducts were significantly reduced in mice
      receiving aristolochic acid plus probenecid compared with mice treated with
      aristolochic acid alone. Thus, we establish the nephroprotective effect of
      probenecid, an inhibitor of organic acid transporters, in vivo toward acute
      proximal tubular epithelial cell toxicity in a mouse model of aristolochic acid
      nephropathy.

PMID- 22854642
TI  - Greater variability in kidney function is associated with an increased risk of
      death.
AB  - Intra-individual variability in kidney function is a common phenomenon; however,
      predictors of kidney function variability and its prognostic significance are not
      known. To examine this question, we assembled a cohort of 51,304 US veterans with
      an estimated glomerular filtration rate (eGFR) <60 ml/min at the end of the study
      period and who had at least two eGFR measurements during the previous 3 years.
      Variability in kidney function was defined for each patient as the coefficient of
      variation of the regression line fitted to all outpatient measures of eGFR during
      this time frame. In adjusted analyses, blacks, women, and those with Current
      Procedural Terminology and ICD-9-CM diagnostic codes for hypertension, diabetes,
      cardiovascular disease, peripheral artery disease, chronic lung disease,
      hepatitis C, dementia, acute kidney injury, and those with a greater number of
      hospitalizations had greater variability in eGFR. After a median follow-up of 4.9
      years, there were 23.66%, 25.68%, and 31.23% deaths among patients in the lowest,
      intermediate, and highest tertiles of eGFR variability, respectively. Compared
      with the referent (those in the lowest tertile), patients in the highest tertile
      had a significantly increased risk of death with a hazard ratio of 1.34 (1.28
      1.40), an association consistently present in all sensitivity analyses. Thus, our
      results demonstrate that greater variability in kidney function is independently
      associated with increased risk of death.

PMID- 22854644
TI  - Mild elevation of urinary biomarkers in prerenal acute kidney injury.
AB  - Prerenal acute kidney injury (AKI) is thought to be a reversible loss of renal
      function without structural damage. Although prerenal and intrinsic AKI
      frequently coexist in clinical situations, serum creatinine and urine output
      provide no information to support their differentiation. Recently developed
      biomarkers reflect tubular epithelial injury; therefore, we evaluated urinary
      biomarker levels in an adult mixed intensive care unit (ICU) cohort of patients
      who had been clinically evaluated as having prerenal AKI. Urinary L-type fatty
      acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL),
      interleukin-18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), and albumin in
      patients with prerenal AKI showed modest but significantly higher concentrations
      than in patients with non-AKI. We also conducted a proof-of-concept experiment to
      measure urinary biomarker excretion in prerenal AKI caused by volume depletion.
      Compared with cisplatinum and ischemia-reperfusion models in mice, volume
      depletion in mice caused a modest secretion of L-FABP and NGAL into urine with
      more sensitive response of L-FABP than that of NGAL. Although no histological
      evidence of structural damage was identified by light microscopy, partial kidney
      hypoxia was found by pimonidazole incorporation in the volume depletion model.
      Thus, our study suggests that new AKI biomarkers can detect mild renal tubular
      damage in prerenal acute kidney injury.

PMID- 22854643
TI  - Autophagy in proximal tubules protects against acute kidney injury.
AB  - Autophagy is induced in renal tubular cells during acute kidney injury; however,
      whether this is protective or injurious remains controversial. We address this
      question by pharmacologic and genetic blockade of autophagy using mouse models of
      cisplatin- and ischemia-reperfusion-induced acute kidney injury. Chloroquine, a
      pharmacological inhibitor of autophagy, blocked autophagic flux and enhanced
      acute kidney injury in both models. Rapamycin, however, activated autophagy and
      protected against cisplatin-induced acute kidney injury. We also established a
      renal proximal tubule-specific autophagy-related gene 7-knockout mouse model
      shown to be defective in both basal and cisplatin-induced autophagy in kidneys.
      Compared with wild-type littermates, these knockout mice were markedly more
      sensitive to cisplatin-induced acute kidney injury as indicated by renal
      functional loss, tissue damage, and apoptosis. Mechanistically, these knockout
      mice had heightened activation of p53 and c-Jun N terminal kinase, the signaling
      pathways contributing to cisplatin acute kidney injury. Proximal tubular cells
      isolated from the knockout mice were more sensitive to cisplatin-induced
      apoptosis than cells from wild-type mice. In addition, the knockout mice were
      more sensitive to renal ischemia-reperfusion injury than their wild-type
      littermates. Thus, our results establish a renoprotective role of tubular cell
      autophagy in acute kidney injury where it may interfere with cell killing
      mechanisms.

PMID- 22854645
TI  - Summary of the KDIGO guideline on anemia and comment: reading between the
      (guide)line(s).
AB  - The kidney disease improving global outcomes (KDIGO) clinical practice guideline
      for anemia in chronic kidney disease (CKD) is designed to assist health-care
      providers in treating CKD patients with anemia. A guideline is not intended to
      define a standard of care, and should not be construed as one, nor should it be
      interpreted as prescribing an exclusive course of management. It is intended to
      provide information and to allow the practitioner to make an informed decision,
      based on evidence and expert judgment. Every health-care professional making use
      of these recommendations is responsible for evaluating the appropriateness of
      applying them in any particular clinical situation. Owing to the general nature
      of a guideline, it is sometimes difficult to translate it to an individual
      patient's condition. As the primary goal is to improve patient care, we have
      decided to focus on practical clinical aspects of the KDIGO anemia guideline.

PMID- 22854647
TI  - Serotonin 1A receptors in the action of antipsychotic drugs: comment on
      'Measurement of the serotonin 1A receptor availability in patients with
      schizophrenia during treatment with the antipsychotic medication ziprasidone' by
      Frankle et al. 2011; 25(6): 734-743.

PMID- 22854646
TI  - Sensitive and specific assays for C3 nephritic factors clarify mechanisms
      underlying complement dysregulation.
AB  - C3 nephritic factors are autoantibodies that prolong the half-life or prevent
      regulation of the alternative pathway C3 convertase, resulting in uncontrolled
      complement activation. They are strongly associated with renal disease but their
      role in pathogenesis remains controversial. Here we optimized and compared a
      panel of assays to identify and interrogate nephritic factor activities. Of 101
      patients with histologic or clinically evident disease, 48 were positive in some
      or all assays. In the presence of properdin, binding of autoantibody was detected
      in 39 samples and convertase stabilization was detected in 36. Forty-two of 48
      nephritic factors tested prevented convertase decay by factor H, and most of
      these by decay accelerating factor (28) and complement receptor 1 (34).
      Representative properdin-independent nephritic factors had no effect on C5
      cleavage and terminal pathway activity, while properdin-dependent nephritic
      factors enhanced activity. Biacore analysis of four purified IgG samples
      confirmed resistance to decay and showed that properdin-independent nephritic
      factors increased convertase half-life over 50-fold, whereas properdin-dependent
      nephritic factors increased the half-life 10- to 20-fold and also increased
      activity of the C3 convertase up to 10-fold. Thus, our study provides a rational
      approach to detect and characterize nephritic factors in patients.

PMID- 22854648
TI  - Mortality in schizophrenia.

PMID- 22854649
TI  - Evidence for mitoxantrone-induced block of inwardly rectifying K(+) channels
      expressed in the osteoclast precursor RAW 264.7 cells differentiated with
      lipopolysaccharide.
AB  - BACKGROUND/AIMS: Mitoxanthrone (MX) is an anthracenedione antineoplastic agent.
      Whether this drug and other related compounds have any effects on ion currents in
      osteoclasts remains largely unclear. METHODS: In this study, the effects of MX
      and other related compounds on inwardly rectifying K(+) current (I(K(IR))) were
      investigated in RAW 264.7 osteoclast precursor cells treated with
      lipopolysaccharide. RESULTS: The I(K(IR))in these cells are blocked by BaCl(2) (1
      mM). MX (1-100 uM) decreased the amplitude of I(K(IR)) in a concentration
      dependent manner with an IC(50) value of 6.4 uM. MX also slowed the time course
      of I(K(IR)) inactivation elicited by large hyperpolarization. Doxorubicin (10
      uM), 17beta-estradiol (10 uM) and tertiapin (1 uM) decreased the I(K(IR))
      amplitude in these cells. In bafilomycin A(1)-treated cells, MX-mediated block of
      I(K(IR)) still existed. In cell-attached configuration, when the electrode was
      filled with MX (10 uM), the activity of inwardly rectifying K(+) (Kir) channels
      was decreased with no change in single-channel conductance. MX-mediated reduction
      of channel activity is accompanied by a shortening of mean open time. Under
      current-clamp conditions, addition of MX resulted in membrane depolarization.
      Therefore, MX can interact with the Kir channels to decrease the I(K(IR))
      amplitude and to depolarize the membrane in these cells. CONCLUSION: The block by
      this drug of Kir2.1 channels appears to be one of the important mechanisms
      underlying its actions on the resorptive activity of osteoclasts, if similar
      results occur in vivo. Targeting at Kir channels may be clinically useful as an
      adjunctive regimen to anti-cancer drugs (e.g., MX or doxorubicin) in influencing
      the resorptive activity of osteoclasts.

PMID- 22854650
TI  - Parenting practices, parental attachment and aggressiveness in adolescence: a
      predictive model.
AB  - The aim of this study was twofold: a) to test the mediation role of attachment
      between parenting practices and aggressiveness, and b) to clarify the
      differential role of mothers and fathers with regard to aggressiveness. A total
      of 554 adolescents (330 girls and 224 boys), ages ranging between 16 and 19,
      completed measures of mothers' and fathers' parenting practices, attachment to
      mother and to father, and aggressiveness. Acceptance/involvement of each parent
      positively predicted an adolescent's attachment to that parent, and
      coercion/imposition negatively predicted attachment to a lesser extent. Using
      structural equation modeling, a full mediation model provided the most
      parsimonious explanation for the data. With attachment in the model, the paths
      between the two parenting practices and aggressiveness were minor and
      statistically non-significant. Only attachment to the father, was predictive of
      adolescents' aggressiveness. Results are discussed in the light of the importance
      of the father-son/daughter relationship in adolescence.

PMID- 22854651
TI  - Less gastrointestinal toxicity after adjuvant radiotherapy on a small pelvic
      field compared to a standard pelvic field in patients with endometrial carcinoma.
AB  - OBJECTIVE: Radiotherapy is associated with short-term and long-term morbidity.
      This study compared toxicity rates among patients with endometrial carcinoma (EC)
      treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic
      field (SmPF) in comparison with a standard pelvic field (StPF) or an extended
      field (EF). METHODS: Patients with EC preoperatively diagnosed with high-grade
      histological disease (grade 3 endometrioid, papillary serous, clear cell, and
      mixed tumor type) or cervical involvement were treated with total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy in the
      University Medical Center Groningen between 1999 and 2008. Patients who received
      adjuvant EBRT were included in this study. External beam radiation therapy on
      SmPF (includes only the central pelvis and proximal vagina) was applied in case
      of negative lymph nodes after adequate lymphadenectomy (>=10 lymph nodes removed
      at the bilateral obturator and external iliac nodal stations). In case of
      positive pelvic lymph nodes or inadequate lymphadenectomy, EBRT on StPF was
      given. External beam radiation therapy on EF was applied in case of common iliac
      and/or para-aortic lymph node metastases. Retrospectively, using the Common
      Terminology Criteria for Adverse Events v3.0, acute toxicity was scored during
      radiotherapy, whereas late toxicity was scored, from 3 months onward after
      treatment. RESULTS: Toxicity could be evaluated in 75 patients treated with SmPF
      (n = 33), StPF (n = 28), and EF EBRT (n = 14). Most patients with late adverse
      events had also reported toxicity during radiotherapy (71%). The most common late
      adverse events were gastrointestinal tract related, more frequently present in
      the StPF group (60.7%) compared to SmPF (33.3%; P = 0.032). In particular, nausea
      and anorexia were more frequent in the StPF group (32.1%) compared to the SmPF
      group (3.0%; P = 0.004), as well as ileus (14.3% vs 0%, P = 0.039, respectively).
      CONCLUSIONS: Treatment with adjuvant EBRT on SmPF results in less
      gastrointestinal late adverse events compared to treatment with EBRT on StPF in
      patients with surgically staged EC.

PMID- 22854652
TI  - Diagnostic value of serum human epididymis protein 4 (HE4) in ovarian carcinoma:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: Human epididymis protein 4 (HE4), a precursor of human epididymis
      protein, has been recently identified as a new promising serum biomarker for
      ovarian carcinoma. We performed a systematic review of studies that investigated
      the use of HE4 in the diagnosis of ovarian cancer in patients with pelvic or
      gynecological masses. We also evaluated the diagnostic performance of HE4 for
      differentiating between patients with benign gynecological disease and those with
      ovarian cancer. METHODS: We searched PubMed database (1990-2011) to collect
      articles in English that evaluated the diagnostic value of HE4 in patients with
      gynecological or pelvic masses. Two reviewers independently assessed the
      methodological quality of each study using the quality assessment of diagnostic
      accuracy studies tool. The data were analyzed using Meta-Disc1.4 software. Meta
      analysis of the reported sensitivity and specificity of each study and summary
      receiver operating characteristic (SROC) curve were performed. RESULTS: A total
      of 9 studies involving 1807 women were included. When the control group was
      composed of healthy women, the pooled sensitivity and specificity for HE4 in
      diagnosing ovarian cancer were 83% (95% confidence interval [CI], 77%-88%) and
      90% (95% CI, 87%-92%), respectively. The area under the SROC curve was 0.9271.
      When the control group was composed of women with benign disease, the pooled
      sensitivity and specificity for HE4 were 74% (95% CI, 69%-78%) and 90% (95% CI,
      87%-92%). The area under the SROC curve was 0.8853. CONCLUSION: The current
      analysis indicated that HE4 may be a valuable marker in the diagnosis of ovarian
      carcinoma. Serum HE4 detection is not only a useful preoperative test for
      predicting the benign or malignant nature of pelvic masses but has a potential to
      be used as an initial step in ovarian cancer screening strategy.

PMID- 22854653
TI  - Temporal trends in the relative survival among women with cervical cancer in
      Canada: a population-based study.
AB  - OBJECTIVE: Cervical cancer was estimated to affect approximately 1300 women in
      Canada in 2011, and 350 women were expected to die from this disease. We
      estimated the trends in the relative survival ratio for patients diagnosed with
      epithelial invasive cervical cancer in Canadian population during the period 1992
      2005. METHODS: A flexible parametric model was used to estimate the relative
      survival ratio. Relative survival ratio is defined as the observed survival among
      patients with cancer divided by the expected survival in the general population.
      We incorporated age group, histology of tumor, geographical region, and year of
      diagnosis in the model to predict 2- and 5-year relative survival ratios.
      RESULTS: A total of 13,424 patients with a diagnosis of epithelial invasive
      cervical cancer were included in this analysis, whose mean (SD) age was 49.3
      (16.0) years at the time of diagnosis. The histologic classification of the
      cervical tumor was squamous for 75.4% of the cases followed by glandular for
      18.5% of the cases. Other epithelial tumors accounted for 6.2% of the cases. The
      same pattern was observed for all regions. The glandular and the "other
      epithelial" cancers had the best and worst survival, respectively. Fifty percent
      of all cases were diagnosed in Ontario. CONCLUSIONS: This article indicates
      gradual improvements for relative survival ratio for all age groups, all types of
      tumor, and all geographical regions in Canada during the 1992-2005 period. The
      improvements may be related to evolutions in screening, diagnosis, and treatment.
      Further progress may be achieved by extending the screening coverage, possibly
      changing the screening test, or advances in treatment.

PMID- 22854654
TI  - Extended-field intensity-modulated radiotherapy and concurrent cisplatin-based
      chemotherapy for postoperative cervical cancer with common iliac or para-aortic
      lymph node metastases: a retrospective review in a single institution.
AB  - OBJECTIVE: Retrospectively, to assess the toxicity of delivering postoperative
      extended-field intensity-modulated radiotherapy (EF-IMRT) and concurrent
      cisplatin chemotherapy for patients with cervical cancer with a pathologically
      confirmed positive common iliac node and/or a para-aortic node. METHODS: Each
      patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. The
      clinical target volume included regional lymph node regions (obturator; common,
      internal, and external iliac nodal regions; presacral region; and para-aortic
      regions) and the upper 2.0 cm of the vagina and paravaginal soft tissue lateral
      to the vagina. The acute and late toxicity were scored using the Common
      Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy
      Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS:
      Fifty-eight patients were treated with postoperative EF-IMRT and concurrent
      cisplatin chemotherapy. The median follow-up was 34 months. Eighteen patients
      (31%) had recurrence. The region of recurrence was in-field in 2 patients (3.4%)
      and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal,
      genitourinary, and hematologic toxicity occurred in 2, 1, and 11 patients,
      respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen
      patients experienced ovarian transposition; of these, 10 patients (77%)
      maintained ovarian function. Forty-one patients (71%) were alive at the last
      follow-up. CONCLUSIONS: Concurrent cisplatin chemotherapy with postoperative EF
      IMRT was safe and well tolerated. The acute and late toxicities are acceptable.
      The locoregional control rates are hopeful, although distant metastases continue
      to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity
      to preserve endocrine function for patients with ovarian transposition.

PMID- 22854655
TI  - [Le Fort I osteotomy and bone graft].
AB  - Preprosthetic surgery aiming implants insertion is recent. It is the result of
      the increasing demand for implant bone prosthesis, even in cases of bony mass
      deficit. Treatment of major bony atrophy with maxilla-mandible class III
      relationship has been proposed with combined correction of the discrepancy and
      bone reconstruction. This was the beginning of the Le Fort 1 and bone grafting
      reconstruction technique. This technique is nowadays one of the classic
      procedures performed in implant preprosthetic maxillar surgery. We here report
      the technique we recommend and its most usual variations.

PMID- 22854656
TI  - Emissions and photocatalytic selectivity of SrWO4:Ln3+ (Eu3+, Tb3+, Sm3+ and
      Dy3+) prepared by a supersonic microwave co-assistance method.
AB  - The chemical effects of high intensity ultrasound and microwave irradiation on
      lanthanide (Eu(3+), Tb(3+), Sm(3+) and Dy(3+)) activated SrWO(4) phosphors were
      extensively studied. Four classes of characteristic optically active materials
      (red, green, orange-red and blue-yellow) with striking luminescence were facilely
      prepared under very low temperature (70  degrees C) in 45 min. Particularly,
      Sm(3+), Dy(3+) and Eu(3+) doped strontium tungstates were visible-light driven
      emissive. The photocatalytic properties of these luminescent lanthanide doped
      tungstates were systematically examined by investigating the degradation behavior
      of different dyes.

PMID- 22854657
TI  - Cancer vaccines: are we there yet?
AB  - For nearly two decades there has been an abundance of research and clinical
      development programs underway to develop active specific immunotherapies, to
      educate the patient's immune response, specifically the T-cell immunity and
      memory, to recognize and destroy tumor cells by cell-mediated cellular toxicity.
      While many of these technology platforms achieved promising results in
      preclinical and clinical phase I and II clinical trials, essentially all but one
      have failed to achieve FDA market approval as a therapeutic drug product.

PMID- 22854658
TI  - Challenges in the development of an autologous heat shock protein based anti
      tumor vaccine.

PMID- 22854659
TI  - Inter-tumor heterogeneity.
AB  - Advances in the molecular study of cancer have focused on biomarkers in the
      setting of tumor-driving mutations within the great heterogeneity of the tumor
      genomic landscape. It is clearly recognized now that even two tumors originating
      from the same organ even if histological they appear similar their behavior and
      response to therapy can be different. These findings have increased interest and
      research to find truly prognostic and predictive biomarkers to serve as tools in
      better assessing the natural course of disease and response to treatments in the
      hope of truly individualizing cancer therapy in the future.

PMID- 22854661
TI  - Evaluation of immune response following one dose of an AS03A-adjuvanted H1N1 2009
      pandemic influenza vaccine in Japanese adults 65 years of age or older.
AB  - OBJECTIVE: This study assessed the immunogenicity, long-term persistence of
      immune response and safety of a single dose of an A/California/07/2009 H1N1
      pandemic influenza vaccine adjuvanted with AS03 (alpha-tocopherol and squalene
      based oil-in-water emulsion Adjuvant System) in subjects >= 65 y of age
      (NCT01114620). RESULTS: At Day 21, the HI immune response met all three European
      guidance criteria [seroconversion rate (SCR): 60.0%; seroprotection rate (SPR):
      64.0%; geometric mean fold rise (GMFR): 10.2] and the US guidance criterion for
      SCR. At month 6, the HI immune response against the A/California/07/2009 H1N1
      strain persisted but at levels lower than that observed at Day 21 (SCR: 38.8%;
      SPR: 42.9%; HI antibody geometric mean titer: 27.6); the European regulatory
      guidance criteria for SCR and GMFR were still met. Overall, the vaccine was well
      tolerated. METHODS: In this open-label, single group study, 50 subjects received
      one dose of the 3.75 ug hemagglutinin (HA) AS03-adjuvanted H1N1 2009 vaccine.
      Immunogenicity assessments were made before vaccination, 21 days and six months
      after vaccination using hemagglutination inhibition (HI) and microneutralization
      assays. Immunogenicity end points were based on US and European regulatory
      criteria. CONCLUSION: A single dose of the 3.75 ug HA AS03-adjuvanted H1N1 2009
      pandemic vaccine induced immune responses against the vaccine strain that met the
      European regulatory guidance criteria at day 21 in the elderly Japanese
      population; the immune response persisted at lower levels at month 6. No safety
      concerns were identified. These results suggest that two vaccine doses might be
      useful for the elderly population to improve antibody induction and persistence.

PMID- 22854662
TI  - A tale of two pities: autologous melanoma vaccines on the brink.
AB  - This paper reviews and compares two autologous vaccine technologies for human
      melanoma that failed to obtain marketing approval after 10-15 y of clinical
      development-the HSP vaccine invented by Srivastava and developed by the company,
      Antigenics, and the hapten-modified cellular vaccine invented by Berd and
      developed by AVAX Technologies. Both vaccines had a strong basic science
      background with a well-understood mechanism of action. The HSP vaccine failed in
      a phase III pivotal trial, while the haptenized cellular vaccine was never
      adequately tested in a phase III trial because of regulatory and financial
      problems. It is proposed that the phase I-II clinical trials of the HSP vaccine
      neglected to define optimal dose, schedule, and route of administration, which,
      together with safety, are the major reasons for doing such trials. Therefore, the
      phase III trial was bound to fail because it was based on insufficient
      immunopharmacological information. Developers of the haptenized cellular vaccine
      underestimated the manufacturing and regulatory hurdles inherent to that
      technology and were therefore unable to complete a pivotal trial. Valuable
      lessons can be learned by acknowledging the mistakes made in these attempts to
      bring forward new treatments that could have eased the burdens of melanoma
      patients.

PMID- 22854660
TI  - Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib
      vaccine Quinvaxem ((r))  demonstrating clinical equivalence, suitability of the
      vaccine as a booster and concomitant administration with measles vaccine.
AB  - This double-blind, randomized study evaluated the immunogenicity and safety of
      three production lots of the fully liquid combination DTwP-Hep-Hib vaccine,
      Quinvaxem ((r))  (Crucell, The Netherlands) in 360 healthy infants aged 42-64 d
      old given at 6, 10 and 14 weeks of age (Core Study). The Core Study was followed
      by an open-label Booster Phase evaluating immunogenicity and safety of a booster
      dose of Quinvaxem ((r))  given with either concomitant or deferred measles
      vaccine in 227 infants who completed the Core Study. One month after the third
      dose of Quinvaxem ((r))  immune responses reflecting seroprotection or
      seroconversion were observed in more than 90% of infants for all three vaccine
      lots. Quinvaxem ((r))  elicited a strong booster response as demonstrated by a
      large increase in antibodies against all antigens, which appeared to be
      unaffected by concomitant administration of the measles vaccine. Safety results
      were in line with previous reports for Quinvaxem ((r))  with no unexpected
      adverse events (AEs) being reported. In the Core Study and Booster Phase,
      Quinvaxem ((r))  was well tolerated. No study vaccine-related serious AEs were
      reported. Thus, Quinvaxem ((r))  was immunogenic and well-tolerated when
      administered to infants according to a 6-10-14 week vaccination schedule. The
      three production lots had consistent reactogenicity and immunogenicity profiles.
      The booster dose of Quinvaxem ((r))  was also immunogenic and safe, regardless of
      whether a monovalent measles vaccine was administered concomitantly or one month
      later.

PMID- 22854663
TI  - Comparison of stimulating effect on subpopulations of lymphocytes in human
      peripheral blood by methionine enkephalin with IL-2 and IFN-gamma.
AB  - The aim of this study was to investigate the effects of mechanisms of methionine
      enkephalin (MENK) on lymphocytes in human peripheral blood. We detected CD4+T
      cells, CD8+T cells, CD4+CD25+ regulatory T cells (Treg), dendritic cells (DCs),
      natural killer cells (NK), NKT cells and gammadeltaT cells before and after
      treatment with 10 (-12) M MENK, in cell culture by FCM and RT-PCR. Our findings
      show that MENK stimulating expansion of lymphocyte subpopulationns by inhibiting
      CD4+CD25+ regulatory T cells (Treg), which is unique discovery of our study. We
      may use MENK as a drug to treat cancer patients, whose immune systems are damaged
      by chemotherapy or radiotherapy.

PMID- 22854664
TI  - Immunotherapy with autologous tumor cell vaccines for treatment of occult disease
      in early stage colon cancer.
AB  - At the cellular level it is clear that cancer is a genetic disease arising as a
      clone that expands and grows in an unregulated manner. While it has always been
      presumed that neoplasia is a consequence of somatic cell mutations, only in the
      last few years has the magnitude and diversity of these mutations been elucidated
      by modern DNA sequencing technology. Immunotherapy is the premier biological
      approach to targeted therapy. Target therapies require targets. In this case the
      targets are tumor specific or associated antigens, the proteins expressed from
      these somatic cell mutations. While the immunotherapeutic approach to eliminating
      cancer was launched with the assumption that cancer cells were homogeneous, the
      recent genomic understanding of tumor cells indicates that there is both inter-
      and intra-tumoral heterogeneity. This presentation will discuss the consequences
      of this new knowledge of tumor cell biology to the immunotherapeutic approach to
      treating cancer.

PMID- 22854665
TI  - TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent
      memory responses in HIV-infected adults.
AB  - HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients
      twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/- a TLR9 agonist
      (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal
      polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group
      had significantly higher relative cytokine responses than the placebo group for
      IL-1beta, IL-2R, IL-6, IFN-gamma and MIP-beta, which, did not correlate with IgG
      antibody responses. These findings suggests that CPG 7909 as adjuvant to
      pneumococcal conjugate vaccine induces cellular memory to pneumococcal
      polysaccharides in HIV-patients, independently of the humoral response.

PMID- 22854666
TI  - Comparison of long-term immunogenicity (23 years) of 10 MUg and 20 MUg doses of
      hepatitis B vaccine in healthy children.
AB  - To compare the long-term immunogenicity and seroprotection rates in healthy
      children following 23 years of vaccination with 10 MUg or 20 MUg doses of plasma
      derived hepatitis B vaccine, we revisited all participants from our previous
      randomized controlled trial. At year 23, 81 participants were tested for HBV
      serological markers and HBV-DNA, and a booster dose was given to those with anti
      HBs titer < 10 mIU/mL. After eliminating the interference of a Year 11 booster
      dose and vaccines received outside of the trial, around 50% of participants still
      maintained anti-HBs titers >= 10 mIU/mL in both 10 MUg and 20 MUg groups (p >
      0.05). The peak immune response of vaccination (anti-HBs antibody levels at 12 mo
      after 1st vaccine dose) and Year 11 anti-HBs levels were significantly associated
      with Year 23 seroprotection rates. Most of the participants in both groups,
      regardless of their prior immune status, developed a rapid and robust anamnestic
      antibody response after the booster dose at year 23. No case of clinically
      significant HBV infection was observed during the entire study period of 23 y
      with only one transient HBsAg seroconversion in 10 MUg vaccine group. We
      concluded that seroprotection provided by 10MUg or 20 MUg doses of hepatitis B
      vaccine persists for 23 years in more than half of vaccinated individuals in
      highly HBV-endemic areas, irrespective of 10 MUg or 20 MUg vaccine doses. Future
      studies with larger sample sizes comparing long-term efficacy of various doses of
      plasma-derived and recombinant HBV vaccines are recommended.

PMID- 22854667
TI  - Model-based projections of the population-level impact of hepatitis A vaccination
      in Mexico.
AB  - There are indications of a shift in the pattern of hepatitis A (HAV) in Mexico
      from high to intermediate endemicity, progressively increasing the mean age of
      infection and the proportion of cases which are symptomatic.   This study
      estimated the potential impact of universal infant HAV vaccination in Mexico with
      two doses of HavrixTM at 12 and 18 mo of age on all HAV infections and
      symptomatic HAV infections. We developed a dynamic transmission model that
      accounts for changes in demography and HAV epidemiology. It was calibrated using
      Mexican age-specific seroprevalence and symptomatic HAV incidence data.   With
      70% first-dose coverage and 85% second-dose coverage, the calibrated model
      projected that HAV vaccination would reduce the incidence of all HAV infections
      (symptomatic and asymptomatic) after the first 25 y of vaccination by 71-76%
      (minimum and maximum for different transmission scenarios). The projected
      reduction in cumulative incidence of symptomatic HAV infections over the first 25
      y of vaccination was 45-51%. With 90% first-dose coverage and 85% second-dose
      coverage, the projected reduction in incidence of all HAV infections was 85-93%,
      and the projected reduction in the cumulative incidence of symptomatic HAV
      infections was 61-67%, over a 25-y time frame. Sensitivity analyses indicated
      that second-dose coverage is important under the conservative base-case
      assumptions made about the duration of vaccine protection.   The model indicated
      that universal infant HAV vaccination could substantially reduce the burden of
      HAV disease in Mexico.

PMID- 22854668
TI  - Size of clinical trials and Introductory prices of prophylactic vaccine series.
AB  - Costs of completing the recommended immunization schedule have increased over the
      last decade. Access to prophylactic vaccines may become limited due to financing
      obstacles within current delivery systems. Vaccine prices reflect research and
      development expenses incurred by vaccine manufacturers, including costs
      associated with evaluating candidate vaccines in human subjects. If the number of
      subjects in clinical trials is increasing over time and associated with vaccine
      price, this may help explain increases in prices of vaccine series. We examined
      whether: (A) the initial public- and private-sector prices for recommended
      prophylactic vaccine series licensed and recommended in the US increased from
      2000-2011, (B) the number of human subjects per licensed vaccine increased during
      the time period, and (C) the number of human subjects was associated with the
      initial public-and private-sector prices of the vaccine series. In regression
      analyses of 13 vaccines, approval year was not significantly associated with the
      number of human subjects, initial public-sector prices, or initial private-sector
      prices. While the number of phase II subjects was not significantly associated
      with prices, the numbers of phase III and combined late phase (phases II + III)
      subjects were significantly associated with initial public- and private-sector
      series prices (p < 0.05). The association between number of subjects and initial
      prices demonstrated diminishing marginal increases in price with increasing
      numbers of subjects. These findings may help guide the number of subjects
      required by the FDA in clinical trials, in order to reduce expenses for
      manufacturers and thereby help mitigate increases in initial vaccine series
      prices.

PMID- 22854669
TI  - Military vaccines in today's environment.
AB  - The US military has a long and highly distinguished record of developing
      effective vaccines against pathogens that threaten the armed forces. Many of
      these vaccines have also been of significant benefit to civilian populations
      around the world. The current requirements for force protection include vaccines
      against endemic disease threats as well as against biological warfare or
      bioterrorism agents, to include novel or genetically engineered threats. The cost
      of vaccine development and the modern regulatory requirements for licensing
      vaccines have strained the ability of the program to maintain this broad mission.
      Without innovative vaccine technologies, streamlined regulatory strategies, and
      coordinating efforts for use in civilian populations where appropriate, the
      military vaccine development program is in jeopardy.

PMID- 22854670
TI  - Overview of the cancer vaccine field: are we moving forward?
AB  - Cancer immunotherapy has seen a tremendous number of failures and only few recent
      regulatory successes. This review is a first in a series dedicated to evaluate
      the status of current global clinical pipeline for cancer vaccines. Apart from
      specific areas of medical need which can be addressed by cancer vaccines, the
      analysis of the pipeline by clinical indication suggests that a
      disproportionately large number of candidates is currently developed in prostate,
      breast, lung cancer and melanoma with significant gap of candidates in remaining
      oncology indications. With potential offering and benefits that cancer
      immunotherapy could bring to patient community and society as a whole, we require
      new innovative R&D, improved Antigen Discovery programs and business models to
      fill serious gaps in cancer vaccine R&D pipeline.

PMID- 22854671
TI  - Hepatitis A vaccine should receive priority in National Immunization Schedule in
      India.
AB  - Hepatitis A is an acute, usually self-limiting infection of the liver caused by a
      virus known as hepatitis A virus (HAV). Humans are the only reservoir of the
      virus; transmission occurs primarily through the fecal-oral route and is closely
      associated with poor sanitary conditions. The virus has a worldwide distribution
      and causes about 1.5 million cases of clinical hepatitis each year. The risk of
      developing symptomatic illness following HAV infection is directly correlated
      with age. As many 85% of children below 2 y and 50% of those between 2-5 y
      infected with HAV are anicteric, and among older children and adults, infection
      usually causes clinical disease, with jaundice occurring in more than 70% of
      cases. The infection is usually self-limiting with occasional fulminant hepatic
      failure and mortality. In most developing countries in Asia and Africa, hepatitis
      A is highly endemic such that a large proportion of the population acquires
      immunity through asymptomatic infection early in life. HAV is endemic in India;
      most of the population is infected asymptomatically in early childhood with life
      long immunity. Several outbreaks of hepatitis A in various parts of India have
      been recorded in the past decade such that anti-HAV positivity varied from 26 to
      85%. Almost 50% of children of ages 1-5 y were found to be susceptible to HAV.
      Any one of the licensed vaccines may be used since all have nearly similar
      efficacy and safety profiles (except for post-exposure prophylaxis /
      immunocompromised patients, where only inactivated vaccines may be used). Two
      doses 6 mo apart are recommended for all vaccines. All Hepatitis A vaccines are
      licensed for use in children aged 1 y or older. However in the Indian scenario,
      it is preferable to administer the vaccines at age 18 mo or more when maternal
      antibodies have completely declined. Vaccination at this age is preferable to
      later since it is easier to integrate with the existing schedule, protects those
      who have no antibodies, and protects children by the time they attend day care.
      In India the vaccine against hepatitis A is available for the people who can
      afford it, but the government of India should give this vaccine as a priority in
      the national immunization schedule.

PMID- 22854672
TI  - Importance of circulating antibodies in protection against meningococcal disease.
AB  - Neisseria meningitidis infection results in life-threatening illnesses, including
      bacteremia, sepsis and meningitis. Early diagnosis and treatment are a challenge
      due to rapid disease progression, resulting in high mortality and morbidity in
      survivors. Disease can occur in healthy individuals, however, risk of infection
      is higher in patients with certain risk factors. N meningitidis carriage and case
      fatality rates are high in adolescents and young adults. The absolute incidence
      of meningococcal disease has decreased partially due to increasing meningococcal
      vaccination rates. Maintaining protective levels of circulating antibodies by
      vaccination is necessary for clinical protection against disease. The Centers for
      Disease Control and Prevention Advisory Committee on Immunization Practices
      guidelines recommend vaccination for all individuals aged 11 through 12 years,
      followed by a booster dose at age 16 years for maintenance of protective antibody
      levels throughout the high-risk years. Despite these guidelines, many adolescents
      remain unvaccinated and susceptible to infection and disease.

PMID- 22854674
TI  - India is on the way forward to maternal and neonatal tetanus elimination!
AB  - Tetanus is an acute, potentially fatal disease, caused by a bacterium,
      Clostridium tetani. The disease usually occurs in newborns through infection of
      the unhealed umbilical stump, particularly when the stump is cut with a non
      sterile instrument. NT contributes to 5-7% of neonatal mortality worldwide.
      Several thousand mothers are also estimated to die annually of maternal tetanus.
      MNT elimination relies on promotion of maternal tetanus immunization along with
      safe delivery and avoidance of unsafe abortion and umbilical cord care practices.
      The Government of India (1983) introduced at least two doses of tetanus toxoid
      vaccine (TT) to all pregnant women during each pregnancy as a part of its
      nationwide immunization policy. To date, a total of 15 States including union
      territories of the India have achieved NT elimination. The remaining Indian
      States need to strengthen TT coverage to save the lives of neonates as well as
      mothers from tetanus.

PMID- 22854673
TI  - Yeast expressed foldable quadrivalent Abeta15 elicited strong immune response
      against Abeta without Abeta-specific T cell response in wild C57BL/6 mice.
AB  - Active and passive immunizations with Abeta and Abeta antibodies successfully
      reduced AD pathology and improved cognitive functions in an AD mouse model.
      However, human clinical trials of vaccination with synthetic Abeta(AN1792), were
      halted due to brain inflammation, presumably induced by T cell-mediated immune
      response. In this study, we used Picha pastoris to produce a recombinant peptide
      vaccine, r4 * Abeta15(recombinant 4 * Abeta15), four tandem repeats of Abeta(1
      15) interlinked by spacers . Wild-type mice were injected subcutaneously with
      CFA/IFA as adjuvant. r4 * Abeta15 vaccine elicited high titer anti-Abeta
      antibodies which bound to Abeta plaque in brain tissue from Tg2576 mouse. The
      antibody isotype was mainly IgG(1), indicating anti-inflammatory Th2 type. There
      was no splenocyte proliferation against Abeta peptide, which indicates that the
      r4 * Abeta15 vaccine does not induce Abeta-specific T cellular immune response.
      Thus, r4 * Abeta15 vaccine may be a safe and efficient vaccine for AD.

PMID- 22854675
TI  - Biological heterogeneity of cancer: implication to therapy.
AB  - Despite significant improvements in diagnosis, surgical techniques, and
      advancements in general patient care, the majority of deaths from cancer are
      caused by the continuous growth of metastases that are resistant to conventional
      therapies. In a large number of cancer patients, metastasis may well have
      occurred by the time of diagnosis. The metastases can be located in different
      distant organs and in different regions within a single organ. The major obstacle
      for the eradication of metastases is the biologic heterogeneity of tumor cells
      that constitute primary cancers and metastases. Specifically, by the time of
      diagnosis, malignant neoplasms contain multiple cell populations with diverse
      biological heterogeneity in growth rate, karyotype, cell surface receptors,
      antigenicity, immunogenicity, maker enzymes, gene expression, sensitivity to
      different cytotoxic drugs, invasion, and metastasis. This biologic heterogeneity
      is not restricted to primary lesions. The cellular composition of metastases in
      the same organ or in different organs is heterogeneous, both within a single
      metastasis (intralesional heterogeneity) and among different metastases
      (interlesional heterogeneity). This heterogeneity is due to two major processes:
      the selective nature of the metastatic process, and the rapid evolution and
      phenotypic diversification of clonal tumor cell populations during progressive
      tumor growth resulting from inherent genetic and epigenetic instability of many
      clonal populations of tumor cells.

PMID- 22854676
TI  - Altered serum levels of brain-derived neurotrophic factor in patients with
      pathological gambling.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays important roles in
      neurotransmitter release and synaptic plasticity and has been hypothesized to be
      involved in the development and maintenance of addictive disorders. The objective
      of this study was to investigate alterations of BDNF expression in a non
      substance-related addiction, i.e. pathological gambling (PG). METHODS: Serum
      levels of BDNF were assessed in male patients with PG (n = 14) and healthy
      control subjects (n = 13) carefully matched for sex, age, body mass index,
      smoking status and urbanicity. Symptoms and severity of PG were measured by the
      adapted form of the Yale-Brown Obsessive-Compulsive Scale. RESULTS: BDNF serum
      levels were significantly increased in patients with PG in comparison to healthy
      control subjects (p = 0.016). There were no significant correlations between BDNF
      serum levels and severity of PG or clinical and demographic variables.
      CONCLUSIONS: Our results show alterations of BDNF serum levels in patients
      suffering from a behavioural addiction and suggest that non-substance-related
      addictions like PG might be associated with neuroendocrinological changes similar
      to the changes observed in substance-related addictions.

PMID- 22854677
TI  - New cytosine derivatives as inhibitors of DNA methylation.
AB  - DNA cytosine methylation catalyzed by DNA methyltransferase 1 (DNMT1) is an
      epigenetic method of gene expression regulation and development. Changes in
      methylation pattern lead to carcinogenesis. Inhibition of DNMT1 activity could be
      a good strategy of safe and efficient epigenetic therapy. In this work, we
      present a novel group of cytosine analogs as inhibitors of DNA methylation. We
      show new methods of synthesis and their effect on in vitro reaction of DNA
      methylation. Almost all of analyzed compounds inhibit DNA methyltransferase
      activity in the competitive manner. K(i) values for the most potent compound 4-N
      furfuryl-5,6-dihydroazacytosines is 0.7 MUM. These compounds cause also a
      decrease of 5-methylcytosine (m(5)C) level in DNA of mammalian HeLa and HEK293
      cells.

PMID- 22854678
TI  - Influence of exclusive resistance training on body composition and cardiovascular
      risk factors in overweight or obese children: a systematic review.
AB  - OBJECTIVE: Since the last decade, a significant increase in the prevalence of
      overweight and obesity among children has been reported. Low aerobic fitness and
      a low compliance with endurance sports in such children are theoretical reasons
      to favor the use of resistance training in intervention studies, even though
      positive effects of resistance training on morbidity without accompanying dietary
      modifications are a matter of debate. In this review we summarize the studies
      that have shown the isolated effect of resistance training on body composition
      and cardiovascular risk factors in overweight and obese children. METHOD: We
      systematically reviewed interventional studies that exclusively applied
      resistance training to overweight and obese 3- to 18-year-old children. Outcome
      measurements were body composition or cardiovascular risk factors. RESULTS: Only
      six studies passed the inclusion criteria. All studies preferred an individually
      planned and supervised whole-body resistance training of moderate to submaximal
      intensity during treatment. The mean compliance was 84%. Four studies reported
      significant changes in body composition, with an increase in fat free mass and
      BMI, along with a decrease in fat mass. Three studies analyzed the effect of
      resistance training on cardiovascular risk factors, and only one study reported a
      significant decrease in systolic blood pressure. CONCLUSION: An individually
      planned and supervised whole-body resistance training of moderate to submaximal
      intensity in children seems to be safe and tends to show positive effects on body
      composition. Similar to interventions based on endurance exercise alone or in
      combination with dietary modifications, the effects on cardiovascular risk
      factors cannot be substantiated. In consequence, we suggest to substantiate the
      effect of resistance training on cardiovascular risk factors in overweight and
      obese children in upcoming randomized controlled trials with high case numbers,
      applying both resistance training only and resistance training in combination
      with dietary intervention to get knowledge about whether resistance training
      alone is effectual in the treatment of overweight and obesity in youth or if a
      combination of resistance training and dietary interventions is actually needed.

PMID- 22854679
TI  - High-efficiency dual labeling of influenza virus for single-virus imaging.
AB  - Many viruses invade host cells by entering the cells and releasing their genome
      for replication, which are remarkable incidents for viral infection. Therefore,
      the viral internal and external components should be simultaneously labeled and
      dynamically tracked at single-virus level for further understanding viral
      infection mechanisms. However, most of the previously reported methods have very
      low labeling efficiency and require considerable time and effort, which is
      laborious and inconvenient for researchers. In this work, we report a general
      strategy to high-efficiently label viral envelope and genome for single-virus
      imaging with quantum dots (QDs) and Syto 82, respectively. It was found that
      nearly all viral envelopes could be labeled with QDs with superior stability,
      which makes it possible to realize global and long-term tracking of single virus
      in individual cells. Effectively labeling their genome with Syto 82, about 90% of
      QDs-labeled viruses could be used to monitor the viral genome signal, which may
      provide valuable information for deeply studying viral genome transport. This is
      very important and meaningful to investigate the viral infection mechanism. Our
      labeling strategy has advantage in commonality, convenience and efficiency, which
      is expected to be widely used in biological research.

PMID- 22854680
TI  - Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function.
AB  - BACKGROUND AND AIMS: Epithelial barrier dysfunction is involved in the
      pathogenesis of allergic diseases; the mechanism is to be further understood.
      Ubiquitin E3 ligase A20 (A20) plays a role in maintaining the homeostasis in the
      body. This study aims to investigate the role of A20 in maintaining the
      epithelial barrier function. METHODS: Human intestinal epithelial cell line, Caco
      2 cells, was cultured to monolayers to test the endocytosis and degradation of a
      model allergen, ovalbumin (OVA). The role of A20 in the endosome/lysosome fusion
      in epithelial cells was tested with A20-sufficient and A20-deficient Caco-2 cells
      and visualized by immunocytochemistry. RESULTS: Caco-2 cells could endocytose
      exogenous allergens (OVA) in culture. The endocytic OVA was degraded in A20
      sufficient Caco-2 cells via the mechanism of endosome/lysosome fusion, while the
      A20-deficient Caco-2 monolayers converted the OVA to the basal compartment of
      transwells, which conserved the antigenicity reflected by that it induced T cell
      proliferation in an allergen-specific manner. A20 was required in the fusion of
      endosomes and lysosomes. CONCLUSION: A20 contributes to maintaining the
      epithelial barrier function.

PMID- 22854681
TI  - Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy of
      a single endothelial cell.
AB  - Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR)
      with the use of a slide-on germanium accessory followed by chemometric analysis
      allowed for providing meaningful information about the biochemical composition of
      a single endothelial cell. In this work, the methodology of the ATR-FTIR
      measurements of dried cells and dried cells immersed in water solution is
      presented. The contact of the cell and Ge crystal was set up manually and
      monitored through the integration of the amide I band. Additionally, the cell
      imaging in transreflection mode was tested, but the spectral differences between
      sub-cellular structures were not prominent in the registered spectra. It has been
      shown that the ATR-FTIR method gives better results due to the increased spatial
      resolution and S/R ratio as well as small contribution of the optical artifacts.

PMID- 22854682
TI  - Sleeping habits predict the magnitude of fat loss in adults exposed to moderate
      caloric restriction.
AB  - OBJECTIVE: To verify whether sleep quantity and quality at baseline predict the
      magnitude of fat loss in adults subjected to moderate caloric restriction.
      METHODS: A total of 123 overweight and obese men and women (age, 41.1 +/- 6.0
      years; BMI, 33.2 +/- 3.6 kg/m2 (mean +/- SD)) underwent a weight loss
      intervention consisting of a targeted 600-700 kcal/day decrease in energy intake
      supervised by a dietician. The length of the intervention varied between 15 and
      24 weeks. Body fat mass (dual-energy X-ray absorptiometry), sleep quality (total
      Pittsburgh sleep quality index score) and sleep duration (h/night, self-reported
      from the Pittsburgh sleep quality index) were assessed at both baseline and at
      the end of the weight loss program. RESULTS: The mean weight loss over the
      dietary intervention was 4.5 +/- 3.9 kg, 76% of which came from fat stores. Using
      a multiple linear regression analysis, we observed a significant positive
      relationship between sleep duration and the loss of body fat, both in absolute
      (adjusted beta = 0.72 kg/h; p < 0.05) as well as in relative terms (adjusted beta
      = 0.77%/h; p < 0.01), after adjusting for age, sex, baseline BMI, length of the
      intervention, and change in total energy intake. Furthermore, we observed that a
      better sleep quality at baseline was associated with greater fat mass loss.
      CONCLUSION: This study provides evidence that sleeping habits can influence the
      success of a weight loss intervention and should be taken into consideration when
      one decides to start a diet.

PMID- 22854683
TI  - Looking back to move forward: a view of nursing education through the theoretical
      lens of Dewey, James and Tyler.

PMID- 22854684
TI  - Better prognosis of multiple sclerosis in patients who experienced a full-term
      pregnancy.
AB  - OBJECTIVE: We conducted a longitudinal prospective study to evaluate the long
      term effect of pregnancy on the progression of multiple sclerosis (MS). METHOD:
      Parous female MS patients were extracted from the database of Isfahan multiple
      sclerosis society (IMSS). Through comparing the annual relapsing rate during a
      mean of 4 years before pregnancy versus a mean of 6 years after delivery, MS
      progression influenced by the pregnancy was analyzed. RESULT: 102 female patients
      were included in our study. The mean annual relapsing rate 4 years prior to
      pregnancy was significantly higher than at the subsequent 6 years after delivery
      (1.06 vs. 0.45, p < 0.001). In addition, the annual relapsing rate in years prior
      to pregnancy was significantly higher than each trimester of gestation (p <
      0.001). Furthermore, there was a 2.2-fold increased risk of having a relapse in
      individuals who had experienced more relapses prior to pregnancy, and a 0.8-fold
      decreased in the risk of having more relapses with older age at the onset of MS.
      CONCLUSION: Although the course of MS was deteriorated 3 months after delivery,
      it was not statistically significant comparing annual relapsing rates during the
      years prior to pregnancy. Moreover, the rate of disease progression slowed down
      in the 6-year period monitored after delivery.

PMID- 22854685
TI  - Predictors of cure, amputation and follow-up dropout among patients with mycetoma
      seen at the Mycetoma Research Centre, University of Khartoum, Sudan.
AB  - Complete cure of mycetoma is difficult to achieve and recurrence is common. The
      study objective was to determine the predictors of cure, amputation and follow-up
      dropout among the studied individuals with mycetoma. This prospective study
      included 1544 patients with confirmed mycetoma, of whom 1242 had eumycetoma and
      302 actinomycetoma. They were treated and followed up regularly. Data were
      collected and analysed using logistic regression models to determine the
      predictors. In the eumycetoma group, longer treatment duration (OR=1.9; 95% CI
      1.2-3.1) and absence of history of disease recurrence (OR=24.2; 95% CI 7.7-76.3)
      were significant predictors of increased odds of cure from mycetoma. A lesion
      size of 5-10 cm (OR=0.5; 95% CI 0.3-0.8) or >10 cm (OR=0.7; 95% CI 0.4-1.0) and
      combined medical treatment and surgery (OR=0.004; 95% CI 0.001-0.011) were each
      significant predictors of reduced odds of cure. Follow-up dropout among this
      group was high (54%). Large lesions (5-10 cm, OR=0.5, 95% CI 0.4-0.7; >10 cm,
      OR=0.6; 95% CI 0.5-0.9), amputations (OR=0.3; 95% CI 0.1-0.6) and longer
      treatment duration (OR=0.5; 95% CI 0.4-0.7) were significant predictors of
      reduced odds of follow-up dropout. In the actinomycetoma group, medical treatment
      was the only significant predictor of cure. Follow-up dropout among this group
      was also high (55.6%). Long treatment duration was a significant predictor of
      reduced odds of dropout (OR=0.5; 95% CI 0.3-0.8). There is a great demand for
      effective and efficient mycetoma treatment. Counselling and health education of
      patients is badly needed to encourage early reporting and treatment to reduce
      mycetoma's medical, social and economic impacts.

PMID- 22854686
TI  - [Design and validation of an instrument to assess families at risk for health
      problems].
AB  - BACKGROUND: There is a paucity of screening instruments with a high clinical
      predictive value to identify families at risk and therefore, develop focused
      interventions in primary care. AIM: To develop an easy to apply screening
      instrument with a high clinical predictive value to identify families with a
      higher health vulnerability. MATERIAL AND METHODS: In the first stage of the
      study an instrument with a high content validity was designed through a review of
      existent instruments, qualitative interviews with families and expert opinions
      following a Delphi approach of three rounds. In the second stage, concurrent
      validity was tested through a comparative analysis between the pilot instrument
      and a family clinical interview conducted to 300 families randomly selected from
      a population registered at a primary care clinic in Santiago. The sampling was
      blocked based on the presence of diabetes, depression, child asthma, behavioral
      disorders, presence of an older person or the lack of previous conditions among
      family members. The third stage, was directed to test the clinical predictive
      validity of the instrument by comparing the baseline vulnerability obtained by
      the instrument and the change in clinical status and health related quality of
      life perceptions of the family members after nine months of follow-up. RESULTS:
      The final SALUFAM instrument included 13 items and had a high internal
      consistency (Cronbach's alpha: 0.821), high test re-test reproducibility (Pearson
      correlation: 0.84) and a high clinical predictive value for clinical
      deterioration (Odds ratio: 1.826; 95% confidence intervals: 1.101-3.029).
      CONCLUSIONS: SALUFAM instrument is applicable, replicable, has a high content
      validity, concurrent validity and clinical predictive value.

PMID- 22854687
TI  - [Cardiovascular risk factors among university students].
AB  - BACKGROUND: Cardiovascular diseases are related to particular lifestyle patterns
      and the presence of cardiovascular risk factors (CVRF). AIM: To evaluate the
      presence of CVRF in students from Universidad Austral de Chile (UACh). MATERIAL
      AND METHODS: CVRF were evaluated in 385 university students aged 17 to 26years
      (63% women). Personal background, lifestyle, anthropometry, blood pressure, serum
      lipids and blood glucose were evaluated. RESULTS: Eighty eight percent of
      evaluated students had sedentary habits, 19% had high LDL cholesterol levels, 40%
      had high blood pressure, 28% smoked, 29% were overweight or obese and 20% had
      some stress level. CONCLUSIONS: There is a high frequency of non-healthy
      lifestyles and cardiovascular risk factors in this sample of university students.

PMID- 22854688
TI  - [Relation of genetic variants of CYP2A6 with tobacco dependence and smoking habit
      in Chilean subjects. A pilot study].
AB  - BACKGROUND: Genetic and metabolic factors associated with nicotine metabolism may
      be related to smoking behavior. AIM: To assess the prevalence of allelic and
      genotype variants of CYP2A6 in a sample of Chilean subjects and to evaluate their
      relationship with smoking and tobacco dependence. MATERIAL AND METHODS: The
      genotype frequencies for *2, *3 and *4 of CYP2A6*1 (wild type) gene were
      determined by polymerase chain reaction (PCR) in 54 volunteers. Addiction to
      tobacco was evaluated using the Fagerstrom Test. The association between the
      presence of allelic variants of CYP2A6 and smoking and tobacco dependence was
      evaluated with chi square test. RESULTS: The prevalence of *1, *2 (wt/*2), *3
      (wt/*3 or *31*3) and *4 (del/del) were 92.6%, 3.7%, 0% y 3.7%, respectively. No
      significant association was observed between being a carrier of a variant
      genotype of CYP2A6 and smoking or tobacco dependence. CONCLUSIONS: In this sample
      of Chilean individuals we did not find a relation between any CYP2A6 genotype
      with smoking or tobacco dependence.

PMID- 22854689
TI  - [Evaluation of olfaction in healthy subjects using the Sniffing Sticks battery].
AB  - BACKGROUND: Olfaction dysfunction is linked to neurodegenerative diseases,
      therefore the evaluation of this function is becoming important AIM: To evaluate
      olfaction in healthy participants. MATERIAL AND METHODS: We evaluated 44 healthy
      males and 55 females, aged 21 to 89 years with the Sniffing Sticks battery to
      determine normal values in Chilean population. During the test, participants must
      correctly identify 12 different odors. RESULTS: Normal olfaction, hyposmia and
      anosmia were defined. An age related decline in olfaction was observed,
      especially among males aged 59 years or more. CONCLUSIONS: This study provides
      age and gender specific normal values for the Sniffing Sticks battery.

PMID- 22854690
TI  - [Prevalence of psychiatric disorders among Chilean children and adolescents].
AB  - BACKGROUND: Psychiatric disorders that appear during childhood or adolescence
      should be a public health priority. AIM: To report the results of a national
      representative survey in the Latin American region examining the prevalence of
      DSM-IV psychiatric disorders in children and adolescents. MATERIAL AND METHODS:
      Subjects aged 4 to 18 years were selected using a stratified multistage design.
      The Diagnostic Interview Schedule for Children Version IV (DISC-IV) was used to
      obtain 12-month DSM-IV diagnoses, and was supplemented with questionnaires
      examining family risk factors, socioeconomic status and service use. RESULTS: A
      sample of 1558 children and adolescents (51% males) was evaluated. Fifty three
      percent of the sample were children aged 4 to 11 years and the rest were
      adolescents aged 12 to 18 years. The prevalence rate for any psychiatric disorder
      without impairment was 38.3% (33.5% for boys and 43.3% for girls). The prevalence
      rate was higher among children as compared to adolescents (42.9% and 33.2%,
      respectively). A third of participants receiving a diagnosis sought some form of
      assistance. Nearly a quarter of those using services, did not have a psychiatric
      diagnosis in the past year. Comorbidity was found in 27% of those with a
      disorder, but only 7% had three or more diagnoses. CONCLUSIONS: The prevalence of
      psychiatric disorders in Chile is high among children and adolescents. This study
      highlights the increasing need to re-evaluate mental health services provided to
      children and adolescents in our country.

PMID- 22854691
TI  - [Children with special health care needs: prevalence in a pediatric hospital and
      associated risks].
AB  - BACKGROUND: "Children with special health care needs" (CSHCN) is a novel
      definition for pediatric patients with chronic diseases, adopted by the Chilean
      Pediatric Society in 2008. As life expectancy in Chile increases, prevalence of
      CSHCN is progressively growing, leading to higher health costs. AIM: To describe
      the epidemiological profile and clinical characteristics of hospitalized CSHCN,
      and compare the risk assessment of adverse events during hospitalization using
      two definitions for CSHCN. PATIENTS AND METHODS: A cohort of hospitalized CSHCN
      in a Pediatric Center at Santiago, Chile, was followed from September to December
      2009. Clinical and demographic data were registered in a database, including
      admission to intensive care unit (ICU), nosocomial infections and prolonged
      hospitalization (> 7 days). Incidence ratios for these events were compared
      between CSHCN and non-CSHCN, and between children attended by three or more
      health care professionals (CSHCN-3) and non-CSHCN. RESULTS: Nine hundred twenty
      patients were included (54% male), with a median age 14 months (0-221) and median
      days of hospitalization 4 days (1-229). Prevalence of CSHCN was 60.8% of
      hospitalized children. When using CSHCN definition and comparing with non-CSHCN,
      no excess of risk was documented. On the other hand, prevalence of CSHCN-3 was
      19.9%. Compared to non-CSHCN, these patients had a higher risk of ICU admission
      (relative risk (RR) 1.58; 95% confidence intervals (CI) = 1.22-2.05; p < 0.01),
      nosocomial infections (RR 2.28; 95% CI = 1.54-3.39; p < 0.001) and prolonged
      hospitalization (RR 1.99; 95% CI = 1.52-2.60; p < 0.001). CONCLUSIONS: One in
      five hospitalized children met CSHCN-3 definition. These patients had an
      increased risk of adverse events during their hospitalization compared to non
      CSHCN.

PMID- 22854692
TI  - [Scientific production in clinical medicine and international collaboration
      networks in South American countries].
AB  - BACKGROUND: International collaboration is increasingly used in biomedical
      research. AIM: To describe the characteristics of scientific production in Latin
      America and the main international collaboration networks for the period 2000 to
      2009. MATERIAL AND METHODS: Search for papers generated in Latin American
      countries in the Clinical Medicine database of ISI Web of Knowledge v.4.10 -
      Current Contents Connect. The country of origin of the corresponding author was
      considered the producing country of the paper. International collaboration was
      analyzed calculating the number of countries that contributed to the generation
      of a particular paper. Collaboration networks were graphed to determine the
      centrality of each network. RESULTS: Twelve Latin American countries participated
      in the production of 253,362 papers. The corresponding author was South American
      in 79% of these papers. Sixteen percent of papers were on clinical medicine and
      36% of these were carried out in collaboration. Brazil had the highest production
      (22,442 papers) and the lower percentage of international collaboration (31%).
      North America accounts for 63% of collaborating countries. Only 8% of
      collaboration is between South American countries. Brazil has the highest
      tendency to collaborate with other South American countries. CONCLUSIONS: Brazil
      is the South American country with the highest scientific production and
      indicators of centrality in South America. The most common collaboration networks
      are with North American countries.

PMID- 22854693
TI  - [Differentiation of Entamoeba histolytica from Entamoeba dispar using Gal/GalNAc
      lectin and polymerase chain reaction].
AB  - BACKGROUND: Entamoeba histolytica and Entamoeba dispar are morphologically
      identical. However, the former is highly pathogenic and the latter is not. AIM:
      To differentiate Entamoeba histolytica from Entamoeba dispar through ELISA and
      PCR techniques in Colombian isolates from feces. MATERIAL AND METHODS:
      Descriptive study of Colombian fecal samples from 53 males and 47 women, that
      were positive for the complex E. histolytica/E. dispar on light microscopy.
      Positive samples were cultured on Robinson medium to isolate trophozoites. The
      presence of specific Gal/ GalNAc-lectin was determined by ELISA and polymerase
      chain reaction in genomic DNA, using the combination of three nucleotides that
      recognize a variable region of 16S small subunit ribosomal RNA, generating a 166
      base pair (bp) product for E. histolytica and 752 pb product for E. dispar.
      RESULTS: After verification, only eight of the 100 samples were positive for the
      complex E. histolytica/E. dispar and were cultivated. Isolates were obtained in
      six cultures, one corresponded to E. histolytica and six to E. dispar.
      CONCLUSIONS: The presence of E. histolytica/E. dispar complex was largely
      overestimated with light microscopy. In the few samples where isolates were
      obtained, the technique described differentiated between both strains.

PMID- 22854694
TI  - [Main characteristics of current biomedical research, in Chile].
AB  - BACKGROUND: Biomedical research is a fundamental tool for the development of a
      country, requiring human and financial resources. AIM: To define some current
      characteristics of biomedical research, in Chile. METHODS: Data on entities
      funding bio-medical research, participant institutions, and the number of active
      investigators for the period 2007-2009 were obtained from institutional sources;
      publications indexed in PubMed for 2008-2009 were analysed. RESULTS: Most
      financial resources invested in biomedical research projects (approximately US$
      19 million per year) came from the "Comision Nacional de Investigacion Cientifica
      y Tecnologica" (CONICYT), a state institution with 3 independent Funds
      administering competitive grant applications open annually to institutional or
      independent investigators in Chile. Other sources and universities raised the
      total amount to US$ 26 million. Since 2007 to 2009, 408 investigators
      participated in projects funded by CONICYT. The main participant institutions
      were Universidad de Chile and Pontificia Universidad Catolica de Chile, both
      adding up to 84% of all funded projects. Independently, in 2009,160 research
      projects -mainly multi centric clinical trials- received approximately US$ 24
      million from foreign pharmaceutical companies. Publications listed in PubMed were
      classified as "clinical research" (n = 879, including public health) or "basic
      biomedical research" (n = 312). CONCLUSIONS: Biomedical research in Chile is
      mainly supported by state funds and university resources, but clinical trials
      also obtained an almost equivalent amount from foreign resources. Investigators
      are predominantly located in two universities. A small number of MD-PhD programs
      are aimed to train and incorporate new scientists. Only a few new Medical Schools
      participate in biomedical research. A National Registry of biomedical research
      projects, including the clinical trials, is required among other initiatives to
      stimulate research in biomedical sciences in Chile.

PMID- 22854695
TI  - [Cutaneous tuberculosis. Report of one case].
AB  - BACKGROUND: Tuberculosis is uncommonly located in the skin, corresponding to 1 to
      2% of extrapulmonary forms. We report a 61-year-old woman, referred due to a two
      months history of erythematous plaques covered with honey-colored crusts in the
      left preauricular region and below the chin. The lesions were previously treated
      as pyoderma with poor response. She was otherwise healthy, without any other
      symptom. Skin biopsy showed exudative tuberculoid granulomas with caseation
      necrosis. Koch culture was positive for Mycobacterium tuberculosis. Complementary
      studies ruled out other foci. Lupus vulgaris was diagnosed and antituberculous
      therapy started, achieving regression of cutaneous lesions.

PMID- 22854696
TI  - [AA amyloidosis with cutaneous manifestations. Report of one case].
AB  - BACKGROUND: Systemic amyloidosis is a rare disease that can affect any organ. Its
      clinical manifestations are varied and nonspecific. The skin involvement of this
      disease is common and can be easily recognized on physical examination. We report
      a 57-year-old male presenting with a two years history of malaise, dyspnea and
      myalgias. On physical examination, ungueal dystrophy, orange pigmentation of
      eyelids with periocular petechiae and mild macroglossia were observed. Incisional
      biopsies of the eyelids, cheeks and hands were obtained. The pathological study
      demonstrated amyloid deposits. Since protein electrophoresis was normal, the
      diagnosis of AA amyloidosis was postulated.

PMID- 22854697
TI  - [Spurious hypoxemia due to hyperleukocytosis. Report of one case].
AB  - BACKGROUND: Arterial gasometry is considered the gold standard for establishing a
      diagnosis of respiratory failure of any etiology. However, there are some
      circumstances in which it loses specificity, making necessary to consider other
      tests such as pulse oximetry to adequately determine hypoxemia. We report a 67
      years old patient with sudden hypoacusia, right hemiparesis and polypnea. His
      laboratory exams on admission, showed extreme hypoxemia in several readings,
      without correlation to the patient's clinical condition nor the pulse oximetry,
      and a leukocytosis of 800.000 cells x ml, with many immature cells. Chronic
      myeloid leukemia was diagnosed and treatment with hydroxyurea was initiated,
      achieving normalization in the arterial gases in accordance with the fall of the
      white cell count. Interpretation of laboratory findings according to the general
      clinical context of the patient allowed to suspect a spurious hypoxemia, saving
      the patient from unnecessary and risky interventions.

PMID- 22854698
TI  - [Cocaine-induced vascular damage. Report of one case].
AB  - BACKGROUND: Cocaine abuse is associated with an increased risk of cardiac and
      cerebrovascular events, such as myocardial infarction, sudden cardiac death, and
      ischemic stroke. The underlying mechanisms leading to these complications are not
      fully understood although intravascular thrombus formation and accelerated
      atherosclerosis are prominent findings. We report a 39-year-old male addicted to
      cocaine, who presented with three consecutive ischemic events characterized by an
      acute myocardial infarction and two ischemic strokes complicated by cardiac
      failure and severe neurological sequelae. The pathophysiology of cocaine-induce
      vascular damage and the management of the ischemic complications are discussed.

PMID- 22854699
TI  - [Soy isoflavones and human health: breast cancer and puberty timing].
AB  - BACKGROUND: Accumulated exposure to high levels of estrogen is associated with an
      increased incidence of breast cancer. Thus, factors such as early puberty, late
      menopause and hormone replacement therapy are considered to be risk factors,
      whereas early childbirth, breastfeeding and puberty at a later age are known to
      consistently decrease the lifetime breast cancer risk. Epidemiological studies
      suggest that consumption of isoflavones correlates with a lower incidence of
      breast cancer. Data from human intervention studies show that the effects of
      isoflavones on early breast cancer markers differ between pre- and post
      menopausal women. The reports from experimental animals (rats and mice) on
      mammary tumors are variable. These results taken together with heterogeneous
      outcomes of human interventions, have led to a controversy surrounding the intake
      of isoflavones to reduce breast cancer risk. This review summarizes recent
      studies and analyzes factors that could explain the variability of results. In
      mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of
      isoflavones on the estrogen receptor and their capacity to act as agonists or
      antagonists. On the issue of puberty timing, we analyze the mechanisms by which
      girls, but not boys, with higher prepuberal isoflavone intakes appear to enter
      puberty at a later age.

PMID- 22854700
TI  - [Evolutionary perspective of eating disorders].
AB  - BACKGROUND: Evolutionary theory has contributed with physiological, psychological
      and behavioral explanations to the comprehension and treatment of eating
      disorders (ED). The aim of this review is to analyze the relationship between ED
      and the attachment theory and natural selection based hypotheses (famine flight,
      reproductive suppression and intrasexual competition). Insecure attachment is
      characteristic of ED and significantly interferes in the individuation
      developmental process. Maternal attachment is usually ambivalent; mainly avoidant
      in anorexics and anxious in bulimics. Anorexic syndrome evokes ancestral adaptive
      mechanisms to face food scarcity, status achievement and threat of group
      exclusion. Suppression of reproductive capacity in anorexics, favored by family
      dynamics, represents a self-sacrifice to obtain the benefit of its members
      through genetic altruism. Feminine intrasexual competence is related to nubile
      features in order to attract and retain high quality and long-term partners.
      Therefore, from an evolutionary perspective, ED symptomatology may be described
      as a self-destructive adaptive state of lack of control, in response to a
      particular genetic phenotype plasticity, environmental factors and cognitive
      processes.

PMID- 22854701
TI  - [Guy de Maupassant: medical aspects of his lustful and creative life].
AB  - BACKGROUND: The French writer Guy de Maupassant is considered one of the most
      important story-tellers of all times. In his short life, he produced relevant
      works which are full of interesting medical descriptions, as sleep palsy and
      unconscious memory, depicted on his famous tale The Horla. Furthermore, many of
      his novels and tales contain precise and very insightful descriptions of
      physicians, many of whom he contacted because of suffering severe migraine.
      Maupassant became psychotic on his last years as a result of neurosyphilis and
      died in an asylum. In this review, we analyze some medical aspects of his intense
      life and provide references of unknown medical descriptions in his works.

PMID- 22854702
TI  - [Evaluation of a faculty development program in curriculum development for
      program directors of medical specialties].
AB  - BACKGROUND: Few medical teaching institutions provide faculty development in
      curriculum development to program directors of medical specialties (PD), despite
      the increased demand for renewal of residency programs and the evaluation of
      outcomes. AIM: To describe and evaluate a training program in curriculum
      development for PD developed in 2008 and 2009. MATERIAL AND METHODS: Thirty PD
      attended an on campus course of fifteen hours. Evaluation was done using
      Kirkpatrick model through an end-of-course questionnaire, a retrospective
      pre/post self-assessment test of skills, the assessment of learning and the final
      projects developed by PD. RESULTS: All PD finished the course and answered the
      questionnaire. In level 1 (Reaction), 100% reported high satisfaction and would
      recommend it highly to others, with perceived mean achievement of course
      objectives of 81%. In level 2 (Learning), all the differences between the
      retrospective pre and posttest were statistically significant (p < 0.01), and
      achievement of learning was in average 82.9%. In level 3 (Behavior), 100% felt
      they would apply what was learnt and 17 PD (57%) sent projects. CONCLUSIONS: This
      model of faculty development was highly accepted by PD and had a positive
      evaluation based in high satisfaction, the improvement in pre/posttest
      assessment, the achievement of learning objectives and the development of
      projects.

PMID- 22854703
TI  - [The outstanding achievements of Adolf Kussmaul].
AB  - BACKGROUND: Adolf Kussmaul was born in Graben, close to Karlsruhe, Germany, on
      February 22,1822. He graduated at Heidelberg University in 1845 and he received
      his medical degree in 1855. He made original descriptions, such as the
      ophthalmoscope, the gastroscope or endoscope, and Kussmaul signs, besides the
      respiration named after him. He was the first to perform a thoracocenteses,
      peritoneal and gastric lavages. He rediscovered progressive bulbar paralysis
      (previously described by Guillaume Duchenne in 1861), polyarteritis nodosa (which
      was described by Karl von Rokitansky en 1852), dyslexia, (described by Thomas
      Willis in 1672) and pulsus paradoxus named after him, but that was reported by
      Richard Lower in 1669. During his 80 years of life, he wrote about different
      issues and topics (cardiology, rheumatology, endocrinology, gastroenterology,
      psychiatry, and neurology). Kussmaul was a student and professional without
      limits in his observation capacity. He preached with his own example in pursuit
      of science: observation, hypothesis, experimentation and analysis.

PMID- 22854705
TI  - Elderly and impoverished cancer patients need urgent help in India.

PMID- 22854706
TI  - [Normal distribution: is it as frequent as it seems?].

PMID- 22854707
TI  - Child physical abuse and concurrence of other types of child abuse in Sweden
      Associations with health and risk behaviors.
AB  - OBJECTIVE: To examine the associations between child physical abuse executed by a
      parent or caretaker and self-rated health problems/risk-taking behaviors among
      teenagers. Further to evaluate concurrence of other types of abuse and how these
      alone and in addition to child physical abuse were associated with bad health
      status and risk-taking behaviors. METHODS: A population-based survey was carried
      out in 2008 among all the pupils in 2 different grades (15 respectively 17 years
      old) in Sodermanland County, Sweden (n=7,262). The response rate was 81.8%. The
      pupils were asked among other things about their exposure to child physical
      abuse, exposure to parental intimate violence, bullying, and exposure to being
      forced to engage in sexual acts. Adjusted analyses were conducted to estimate
      associations between exposure and ill-health/risk-taking behaviors. RESULTS:
      Child physical abuse was associated with poor health and risk-taking behaviors
      with adjusted odds ratios (OR) ranging from 1.6 to 6.2. The associations were
      stronger when the pupils reported repeated abuse with OR ranging from 2.0 to
      13.2. Also experiencing parental intimate partner violence, bullying and being
      forced to engage in sexual acts was associated with poor health and risk-taking
      behaviors with the same graded relationship to repeated abuse. Finally there was
      a cumulative effect of multiple abuse in the form of being exposed to child
      physical abuse plus other types of abuse and the associations increased with the
      number of concurrent abuse. CONCLUSIONS: This study provides strong indications
      that child abuse is a serious public health problem based on the clear links seen
      between abuse and poor health and behavioral problems. Consistent with other
      studies showing a graded relationship between experiences of abuse and poor
      health/risk-taking behaviors our study shows poorer outcomes for repeated and
      multiple abuse. Thus, our study calls for improvement of methods of comprehensive
      assessments, interventions and treatment in all settings where professionals meet
      young people.

PMID- 22854708
TI  - CX(3)CR1(+) macrophages support IL-22 production by innate lymphoid cells during
      infection with Citrobacter rodentium.
AB  - Innate immune cells, such as intestinal epithelial cells, dendritic cells (DCs),
      macrophages, granulocytes, and innate lymphoid cells provide a first line of
      defence to enteric pathogens. To study the role of CX(3)CR1(+) DCs and
      macrophages in host defence, we infected CX(3)CR1-GFP animals with Citrobacter
      rodentium. When transgenic CX(3)CR1-GFP animals are infected with the natural
      mouse pathogen C. rodentium, CX(3)CR1(-/-) animals showed a delayed clearance of
      C. rodentium as compared with (age- and sex-matched) wild-type B6 animals. The
      delayed clearance of C. rodentium is associated with reduced interleukin (IL)-22
      expression. In C. rodentium-infected CX(3)CR1-GFP animals, IL-22 producing
      lymphoid-tissue inducer cells (LTi cells) were selectively reduced in the absence
      of CX(3)CR1. The reduced IL-22 expression correlates with decreased expression of
      the antimicrobial peptides RegIIIbeta and RegIIIgamma. The depletion of
      CX(3)CR1(+) cells by diphtheria toxin injection in CX(3)CR1-GFP * CD11c.DOG
      animals confirmed the role of CX(3)CR1(+) phagocytes in establishing IL-22
      production, supporting the clearance of a C. rodentium infection.

PMID- 22854709
TI  - A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal
      immunopathogenesis.
AB  - Interleukin-22 (IL-22) is a cytokine with epithelial reparative and regenerative
      properties that is produced by Th22 cells and by other immune cell subsets.
      Therefore, we explored the hypothesis that disruption of the gut barrier during
      HIV infection involves dysregulation of these cells in the gastrointestinal
      mucosa. Sigmoid IL-22-producing T cell and Th22 cells were dramatically depleted
      during chronic HIV infection, epithelial integrity was compromised, and microbial
      translocation was increased. These alterations were reversed after long-term
      antiretroviral therapy. While all mucosal IL-22-producing T-cell subsets were
      also depleted very early during HIV infection, at these early stages IL-22
      production by non-T-cell populations (including NKp44+ cells) was increased and
      gut epithelial integrity was maintained. Circulating Th22 cells expressed a
      higher level of the HIV co-receptor/binding molecules CCR5 and alpha4beta7 than
      CD4+ T-cell subsets in HIV-uninfected participants, but this was not the case
      after HIV infection. Finally, recombinant IL-22 was protective against HIV and
      tumor necrosis factor-alpha-induced gut epithelial damage in a validated in vitro
      gut epithelial system. We conclude that reduced IL-22 production and Th22
      depletion in the gut mucosa are important factors in HIV mucosal
      immunopathogenesis.

PMID- 22854710
TI  - Vinpocetine inhibits oligodendroglial precursor cell differentiation.
AB  - BACKGROUND: In multiple sclerosis during periods of remission a limited degree of
      myelin repair can be observed mediated by oligodendroglial precursor cells.
      Phosphodiesterase inhibitors act as anti-inflammatory agents and might hold
      promise for future multiple sclerosis treatment. AIMS: To investigate whether
      phosphodiesterase inhibitors could also influence myelin repair. METHODS: We
      stimulated primary oligodendroglial precursor cells with cilostazol, rolipram and
      vinpocetine and assessed their effects on repair related cellular processes.
      RESULTS: We found that vinpocetine exerted a strong negative effect on myelin
      expression while cilostazol and rolipram did not show such effects. In addition,
      vinpocetine decreased morphological complexities suggesting an overall negative
      impact on oligodendroglial cell maturation. We provide evidence that this is not
      mediated via a blockade of phosphodiesterase-1 but rather by inhibition of IKB
      kinase. CONCLUSION: These findings suggest that vinpocetine via IKB inhibition
      exerts a strong negative impact on oligodendroglial cell maturation and may
      therefore provide the rationale to restrict its application during periods of
      remission in multiple sclerosis patients. This is of particular interest since
      vinpocetine is widely used as a health supplement thought to act as a cognitive
      and memory enhancer for healthy people and patients with neurological or muscle
      diseases.

PMID- 22854711
TI  - Professor Panos Vardas: president of the European Society of Cardiology.

PMID- 22854712
TI  - Four polymorphisms of cholesteryl ester transfer protein gene and coronary
      stenosis in a Tunisian population.
AB  - AIMS: The role of cholesteryl ester transfer protein (CETP) in the development of
      atherosclerosis is under debate. We studied the association of four polymorphisms
      (Taq1B, I405V, R451Q and A373P) in the CETP gene with lipid profile and coronary
      artery disease. METHODS: Four CETP polymorphisms were studied in 316 Tunisian
      patients undergoing coronary angiography. Patients were clinically examined and
      their lipid profiles were estimated. Genotyping was performed using polymerase
      chain reaction-restriction fragment length polymorphism analysis. RESULTS: The
      451Q allele, associated with lower high-density lipoprotein-cholesterol (HDL-C)
      and higher total cholesterol and apolipoprotein B (ApoB) concentrations, was also
      significantly associated with an increased risk of significant stenosis [odds
      ratio (OR) = 1.74, 95% confidence interval (CI) 1.15-2.61, P = 0.007]. The B2
      allele of Taq1B polymorphism had an increase in HDL-C concentration and was
      associated with a decreased risk of coronary stenosis, as described earlier. It
      was also associated with low risk of hypoHDLaemia [OR = 0.615, 95% CI 0.377
      1.002, P = 0.035]. No significant effect of different A373P and I405V alleles was
      found on the lipid profile and on coronary stenosis. When CETP polymorphisms were
      combined in haplotypes possessing R451Q, A373P, I405V, Taq1B polymorphisms, the
      1112 haplotype (where 1 is the wild genotype and 2 represents carriers of the
      variant allele) seems to be the most protective against significant stenosis (OR
      = 0.71, 95% CI 0.188-0.983; P = 0.014), whereas 2111 was probably the most
      atherogenic, with an OR = 2.17, 95% CI 1.06-5.88; P = 0.039. CONCLUSION: The Q
      allele of the R451Q polymorphism was associated with decreased HDL-C, increased
      ApoB concentrations and increased risk of coronary stenosis. In haplotype
      analysis, we found that 1112 seems to be a protective haplotype, whereas 2111 has
      an atherogenic effect in a coronary Tunisian population.

PMID- 22854713
TI  - A simple colorimetric device for rapid detection of Hg2+ in water.
AB  - A 'turn-on' fluorescent colorimetric device for Hg(2+) sensing was built using a
      dual light-emitting diode system. Fluorescence generated from a rhodamine
      derivative (RHD), an indicator for Hg(2+) sensing, was combined with a background
      red light, and the complex light was captured by a commercial charge coupled
      device camera or by the naked eye.

PMID- 22854718
TI  - Nanomolar fluorescent detection of c-di-GMP using a modular aptamer strategy.
AB  - C-di-GMP regulates important processes involved in biofilm formation and
      virulence factors production in several bacteria. Herein we report a simple
      fluorescent strategy that allows for the detection of c-di-GMP (as low as 320 nM)
      using a Vc2 class I riboswitch domain as the sensing region and spinach as the
      fluorescent reporting module.

PMID- 22854719
TI  - Gary Bond and fidelity assessment: the work continues.

PMID- 22854721
TI  - Personal accounts: stepping into a crosswalk.

PMID- 22854722
TI  - Introduction to the Festschrift.

PMID- 22854723
TI  - Advances in fidelity measurement for mental health services research: four
      measures.
AB  - Mental health intervention research requires clear and accurate specification of
      treatment conditions in intervention studies. Measures are increasingly available
      for community-based interventions for persons with serious mental illnesses.
      Measures must go beyond structural features to assess critical processes in
      interventions. They must also balance effectiveness, or adequate coverage of
      active treatment elements, with efficiency, or the degree to which measures may
      be used cost-effectively. The context of their use is changing with the emergence
      of new frameworks for implementation research and quality improvement. To
      illustrate a range of approaches, this article describes four recently developed
      fidelity measures: Cognitive Therapy for Psychosis Adherence Scale, Strengths
      Model Fidelity Scale, Illness Management and Recovery Program Fidelity Scale, and
      Tool for Measurement of ACT. The fidelity measures assess interventions in a
      range of treatment contexts from dyads to teams. Each measure focuses assessment
      resources on critical elements. Each has demonstrated coverage of its target
      intervention and satisfactory psychometric properties and is related to outcomes.
      Measures have been used for training, quality improvement, or certification. They
      assess domains and have uses beyond their nominal position in implementation and
      quality frameworks. This review of recent fidelity measures indicates that
      process components in community-based interventions can be effectively assessed.
      Omission of elements assessing potentially critical active treatment components
      poses risk to both research and practice until there is evidence to demonstrate
      that they are nonessential. Further development of fidelity measurement theory
      and approaches should proceed in conjunction with development of theory and
      methods in implementation science.

PMID- 22854724
TI  - Development and reliability of a measure of clinician competence in providing
      illness management and recovery.
AB  - OBJECTIVE: Illness management and recovery (IMR) is an evidence-based, manualized
      illness self-management program for people with severe mental illness. This study
      sought to develop a measure of IMR clinician competence and test its reliability
      and validity. METHODS: Two groups of subject matter experts each independently
      created a clinician-level IMR competence scale based on the IMR Fidelity Scale
      and on two unpublished instruments used to evaluate provider competence. The two
      versions were merged, and investigators used the initial version to independently
      rate recordings of IMR sessions. Ratings were compared and discussed,
      discrepancies were resolved, and the scale was revised through 14 iterations. The
      resulting IMR Treatment Integrity Scale (IT-IS) includes 13 required items and
      three optional items rated only when the particular skill is attempted. Four
      independent raters then used the IT-IS to score tapes of 60 IMR sessions and 20
      control group sessions. RESULTS: The IT-IS showed excellent interrater
      reliability (.92). A factor analysis supported a one-factor model that showed
      good internal consistency. The scale successfully differentiated between IMR and
      control groups. Reliability and validity of individual items varied widely.
      CONCLUSIONS: The IT-IS is a promising measure of clinician competence in
      providing IMR. The scale could be used for research and quality assurance and as
      a supervisory feedback tool. Future research is needed to examine item-level
      changes, predictive validity of the IT-IS, discriminant validity compared with
      other more structured interventions, and the reliability and validity of the
      scale for nongroup IMR.

PMID- 22854725
TI  - A coding system to measure elements of shared decision making during psychiatric
      visits.
AB  - OBJECTIVE: Shared decision making is widely recognized to facilitate effective
      health care. The purpose of this study was to assess the applicability and
      usefulness of a scale to measure the presence and extent of shared decision
      making in clinical decisions in psychiatric practice. METHODS: A coding scheme
      assessing shared decision making in general medical settings was adapted to
      mental health settings, and a manual for using the scheme was created. Trained
      raters used the adapted scale to analyze 170 audio-recordings of medication check
      up visits with either psychiatrists or nurse practitioners. The scale assessed
      the level of shared decision making based on the presence of nine specific
      elements. Interrater reliability was examined, and the frequency with which
      elements of shared decision making were observed was documented. The association
      between visit length and extent of shared decision making was also examined.
      RESULTS: Interrater reliability among three raters on a subset of 20 recordings
      ranged from 67% to 100% agreement for the presence of each of the nine elements
      of shared decision making and 100% for the agreement between provider and
      consumer on decisions made. Of the 170 sessions, 128 (75%) included a clinical
      decision. Just over half of the decisions (53%) met minimum criteria for shared
      decision making. Shared decision making was not related to visit length after the
      analysis controlled for the complexity of the decision. CONCLUSIONS: The rating
      scale appears to reliably assess shared decision making in psychiatric practice
      and could be helpful for future research, training, and implementation efforts.

PMID- 22854726
TI  - Use of fidelity assessments to train clinicians in the CBT for PTSD program for
      clients with serious mental illness.
AB  - OBJECTIVE: One barrier to disseminating evidence-based practices for persons with
      serious mental illness is the difficulty of training frontline clinicians. This
      study evaluated whether frontline clinicians could be trained to implement an
      empirically supported cognitive-behavioral therapy (CBT) program for
      posttraumatic stress disorder (PTSD) among persons with serious mental illness
      when a standardized fidelity measure was used to provide clinicians with feedback
      on practice cases. METHODS: Twenty-five clinicians (23 master's level) at five
      agency sites were trained in the CBT for PTSD program and delivered it to 35
      clients (practice cases) over six months. Supervisors or consultants used the
      fidelity measure to rate audio-recorded sessions and provide feedback. A
      criterion of competence was established to designate program certification.
      Clients' PTSD and depression symptoms were monitored. Clinicians' satisfaction
      with training was also assessed. RESULTS: Two clinicians dropped out, and 21 of
      the remaining 23 clinicians (91%) achieved program certification with their first
      case; the remaining two (9%) achieved it with their second case. Clients'
      symptoms, measured by the PTSD Checklist and the Beck Depression Inventory,
      decreased significantly during treatment, suggesting clinical benefits of the
      program. Clinicians reported that group supervision was very helpful and written
      feedback was helpful or very helpful. All rated the training as excellent.
      CONCLUSIONS: Results support the feasibility of training frontline clinicians in
      the CBT for PTSD program by using regular feedback based on the fidelity measure
      and indicate that most clinicians can achieve competence in the model with a
      single practice case.

PMID- 22854727
TI  - Early mortality and years of potential life lost among Veterans Affairs patients
      with depression.
AB  - OBJECTIVE: Substantial literature documents excess and early mortality among
      individuals with serious mental illness, but there are relatively few data about
      mortality and depression. METHODS: During fiscal year 2007, data from the U.S.
      Department of Veterans Affairs and the National Death Index were used to
      calculate mean age of death and years of potential life lost (YPLL) associated
      with 13 causes of death among veterans with (N=701,659) or without (N=4,245,193)
      depression. RESULTS: Compared with nondepressed patients, depressed patients died
      younger (71.1 versus 75.9) and had more YPLL (13.4 versus 10.2) as a result of
      both natural and unnatural causes. Depending on the cause of death, depressed
      patients died between 2.5 and 8.7 years earlier and had 1.5 to 6.1 YPLL compared
      with nondepressed patients. CONCLUSIONS: These findings have important
      implications for clinical practice, given that improved quality of care may be
      needed to reduce early mortality among depressed VA patients.

PMID- 22854728
TI  - Racial differences in antidepressant use among older home health care patients.
AB  - OBJECTIVE: The objective of this study was to determine the association of race
      (black and white) with depression diagnosis and antidepressant use among older
      home health care patients. METHODS: Cross-sectional data were obtained from the
      2007 National Home and Hospice Care Survey of patients 65 years and older
      (N=3,157). Data were analyzed by race, antidepressant use, and charted depression
      diagnosis. RESULTS: Whites had greater odds than blacks of receiving a depression
      diagnosis (adjusted odds ratio [AOR]=4.46, 95% confidence interval [CI]=1.52
      13.09). Whites with no depression diagnosis were also more likely to receive an
      antidepressant (AOR=2.62, CI=1.58-4.36); however, the difference in receipt of an
      antidepressant between whites and blacks with a depression diagnosis was not
      significant. CONCLUSIONS: Older blacks were less likely than older whites to
      receive antidepressants, independent of a depression diagnosis. This finding
      suggests that older blacks with depression in home health care may face two
      disparities relative to whites: underdiagnosis and undertreatment of depression.

PMID- 22854729
TI  - Probation officers' perspectives on interagency collaboration for juvenile
      offenders with mental health problems.
AB  - OBJECTIVES: This study examined the interagency collaboration strategies used by
      juvenile probation officers in the treatment of delinquent youths. METHODS:
      Thirty-one juvenile probation officers were interviewed about the strategies they
      use with youths who have mental disorders. Transcriptions of these interviews
      were analyzed with grounded-theory conventions. RESULTS: Interagency
      collaboration was described in a framework of three models. The monitoring model
      involved minimal involvement of probation officers with treatment providers, the
      teamwork model involved collaborative decision making and frequent consultation,
      and the partnership model involved the direct involvement of probation officers
      in the treatment process. CONCLUSIONS: Results of this study provide a framework
      for conceptualizing interagency collaboration and juvenile court authority. This
      framework may be used in case and program planning as well as in research to
      develop evidence-based strategies for the treatment of court-involved youths with
      mental disorders.

PMID- 22854730
TI  - Use of coercion in recovery-oriented care: staying vigilant.

PMID- 22854732
TI  - Establishing directions for qualitative studies of recovery.

PMID- 22854739
TI  - IOM assesses efforts to prevent and treat PTSD among service members and
      veterans.

PMID- 22854733
TI  - Medical students' attitudes about mental illness.

PMID- 22854740
TI  - IOM report highlights inadequacies of the geriatric behavioral health workforce.

PMID- 22854742
TI  - Biomarkers of metal toxicity and histology of Perna viridis from Ennore estuary,
      Chennai, south east coast of India.
AB  - Distribution of heavy metals and its associated histological perturbations were
      studied in the soft tissues of Perna viridis collected from Ennore estuary and
      compared with the less polluted Kovalam coast. The concentration of copper, lead,
      zinc, cadmium, manganese and iron were quantified in gills, digestive gland and
      adductor muscle. The results showed marked differences between the two sites as
      well as significant variations within the tissues. Among the heavy metals
      analyzed, lead and cadmium recorded very low in the soft tissues of mussel. Heavy
      metal levels in tissues of mussel collected from Ennore estuary were in the order
      of gills>digestive gland>adductor muscle, while it was digestive
      gland>gills>adductor muscle in the mussel sampled from Kovalam coast. The
      decreasing trend of metals in the tissues of mussels sampled from both Ennore
      estuary and Kovalam coast was in the order of Fe>Mn>Zn>Cu>Pb>Cd. Overall, the
      highest metal concentrations were found in the mussel collected from Ennore
      estuary. The metal accumulation in the gills and digestive gland of Perna viridis
      was found to be quite high in comparison with the adductor muscle. These soft
      tissues were further investigated by light microscopy and the results were
      compared with the reference site (Kovalam coast). These results suggest that
      thickening of the digestive epithelium, hemocytic infiltration in the gills and
      myodegeneration in the muscle tissue are useful histological biomarkers for heavy
      metal induced stress, and demonstrate that precautions need to be taken in Ennore
      estuary in order to prevent heavy metal pollution that can occur in the future.

PMID- 22854743
TI  - Changes in body burden of mercury, lead, arsenic, cadmium and selenium in infants
      during early lactation in comparison with placental transfer.
AB  - The developing brains of both fetuses and infants are susceptible to
      environmental contaminants. However, the contribution of breast-feeding to the
      element body burden in infants remains unclear. The main objective of this study
      was to investigate the changes in body burden of elements such as methylmercury,
      lead, arsenic, cadmium, and selenium in infants during a 3-month breast-feeding
      period compared with placental transfer of the elements. Element concentrations
      were measured in maternal and umbilical cord (fetus) red blood cells (RBCs) at
      parturition and in infant RBCs at 3 months. Most of the mercury in RBCs is in the
      methyl form, and the total mercury concentration in RBCs reflects methylmercury
      exposure. The mercury level in cord RBCs was approximately 1.5 times higher than
      that in mothers, while in infants, it declined by approximately 60% after 3
      months' breast-feeding. The cord selenium level was similar to the maternal
      level, but declined approximately 75% after 3-months' breast-feeding in infants.
      Lead and arsenic concentrations in cord RBCs were about 60% of the maternal
      levels, and remained constant until the 3-month study period. The cadmium level
      in cord RBCs was about 20% of that in maternal RBCs, and remained almost constant
      until the end of the 3-month study period. In conclusion, although pregnant women
      should pay attention to avoid high methylmercury exposure, element exposure
      through breast-feeding does not pose any great concern in this population.

PMID- 22854744
TI  - Managing metolachlor and atrazine leaching losses using lignite fly ash.
AB  - Application of low cost amendment for pesticide retention in soil is an important
      area of research in environmental sciences. The present study reports the
      potential of coal fly ash (Inderprastha and Badarpur), a waste from thermal power
      stations, for retaining soil applied metolachlor and atrazine within the
      application zone. Both the fly ashes were highly effective in reducing the
      leaching losses of metolachlor and atrazine and at 2% and 5% fly ash amendment
      levels the herbicides were retained in the top 15 cm profile of the column.
      However, fly ashes varied in their capacity in reducing the downward mobility of
      herbicides, as the Inderprastha fly ash was more effective than the Badarpur fly
      ash. Although fly ash contained heavy metals like Cr, Cu or Pb, but they were not
      detected in the leachate. Also, concentration of other metals like Zn, Mn and Fe
      in leachate decreased after fly ash amendment. Results of this study have
      implications in reducing the leaching losses of these herbicides in agricultural
      soils.

PMID- 22854745
TI  - Are metallothioneins equally good biomarkers of metal and oxidative stress?
AB  - Several researchers investigated the induction of metallothioneins (MTs) in the
      presence of metals, namely Cadmium (Cd). Fewer studies observed the induction of
      MTs due to oxidizing agents, and literature comparing the sensitivity of MTs to
      different stressors is even more scarce or even nonexistent. The role of MTs in
      metal and oxidative stress and thus their use as a stress biomarker, remains to
      be clearly elucidated. To better understand the role of MTs as a biomarker in
      Cerastoderma edule, a bivalve widely used as bioindicator, a laboratory assay was
      conducted aiming to assess the sensitivity of MTs to metal and oxidative
      stressors. For this purpose, Cd was used to induce metal stress, whereas hydrogen
      peroxide (H2O2), being an oxidizing compound, was used to impose oxidative
      stress. Results showed that induction of MTs occurred at very different levels in
      metal and oxidative stress. In the presence of the oxidizing agent (H2O2), MTs
      only increased significantly when the degree of oxidative stress was very high,
      and mortality rates were higher than 50 percent. On the contrary, C. edule
      survived to all Cd concentrations used and significant MTs increases, compared to
      the control, were observed in all Cd exposures. The present work also revealed
      that the number of ions and the metal bound to MTs varied with the exposure
      conditions. In the absence of disturbance, MTs bound most (60-70 percent) of the
      essential metals (Zn and Cu) in solution. In stressful situations, such as the
      exposure to Cd and H2O2, MTs did not bind to Cu and bound less to Zn. When
      organisms were exposed to Cd, the total number of ions bound per MT molecule did
      not change, compared to control. However the sort of ions bound per MT molecule
      differed; part of the Zn and all Cu ions where displaced by Cd ions. For
      organisms exposed to H2O2, each MT molecule bound less than half of the ions
      compared to control and Cd conditions, which indicates a partial oxidation of
      thiol groups in the cysteine residues through ROS scavenging. The present results
      suggest that MTs are excellent markers of metal stress, but not of oxidative
      stress.

PMID- 22854746
TI  - Activation level of JNK and Akt/ERK signaling pathways determinates extent of DNA
      damage in the liver of diabetic rats.
AB  - AIMS: Diabetes-related oxidative stress conditions lead to progressive tissue
      damage and disfunctionality. Mechanisms underlying liver pathophysiology during
      diabetes are not fully understood. The aim of this study was to find relationship
      between diabetes-related DNA damage in the rat liver and activities of
      prosurvival signaling pathways. METHODS: Effect of diabetes was analyzed two
      (development stage) and eight weeks (stable diabetes) after single
      intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by
      comet assay, was corelated with oxidative status (plasma level of ROS, liver
      antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK,
      JAK) and transcription factors NF-kappaB p65 and STAT3. RESULTS: Significant DNA
      damage in development stage is accompanied by elevated plasma levels of O(2)(-)
      and H(2)O(2), decreased activities of CAT, MnSOD, and GST in the liver and
      increased activation of proapoptotic JNK signal pathway. Lower DNA damage in
      stable diabetes, is accompanied by elevated plasma level of O(2)(-), restored
      antioxidative liver enzyme activity, decreased activation of JNK and increased
      activation of prosurvival Akt and ERK signal pathways. CONCLUSION: These findings
      indicate that level of DNA damage in diabetic liver depends on the extent of
      oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal
      pathways activation .

PMID- 22854752
TI  - Open-label placebo for major depressive disorder: a pilot randomized controlled
      trial.

PMID- 22854759
TI  - DNA pseudoknot-functionalized sensing platform for chemoselective analysis of
      mercury ions.
AB  - A novel, simple, signal-enhanced electrochemical sensor was designed for
      sensitive and selective determination of mercury ions by using target-triggered
      conformational change of DNA pseudoknots with the assistance of auxiliary DNA
      strands.

PMID- 22854753
TI  - Escherichia coli membranes depleted of SecYEG elicit SecA-dependent ion-channel
      activity but lose signal peptide specificity.
AB  - We have developed a sensitive method to detect the opening of SecA-dependent,
      protein-conducting channels in Xenopus oocytes. In this study, we determined the
      ionic current activities of the SecA-dependent channel from membrane vesicles
      depleted of SecYEG. We found that these SecYEG-depleted membranes produced SecA
      dependent ionic currents in the oocytes, as did membranes containing SecYEG.
      However, reconstituted membranes depleted of SecYEG required higher
      concentrations of SecA to elicit ionic currents like those in membranes
      containing SecYEG. In contrast to membranes containing SecYEG, the proofreading
      capacity of signal peptides was lost for those membranes lacking SecYEG. These
      findings are consistent with loss of signal peptide specificity in channel
      activity from membranes of SecY suppressor or SecY plug domain mutants. The
      signal peptide specificity of the reconstituted membranes, like SecA-liposomes,
      can be restored by the addition of SecYEG proteoliposomes. On the other hand, the
      channel activity efficiency of reconstituted membranes was fully restored, while
      SecA-liposomes could only be partially enhanced by the addition of SecYEG,
      indicating that, in addition to SecYEG, other membrane proteins contribute to the
      efficiency of channel activity. The SecA-dependent channels in membranes that
      lacked SecYEG also lost ion selectivity to monovalent cations but retained
      selective permeability to large anions. Thus, the electrophysiological evidence
      presented here indicates that SecYEG is not obligatory for the channel activity
      of Escherichia coli membranes, as previously shown for protein translocation, and
      that SecYEG is important for maintenance of the efficiency and specificity of
      SecA-dependent channels.

PMID- 22854760
TI  - Kinesin family member 20A is a novel melanoma-associated antigen.
AB  - It has been shown recently that immunotherapy for advanced melanoma is effective.
      However, in order to improve the efficacy of immunotherapy, the identification of
      more specific melanoma-associated antigens is urgently needed. Kinesin family
      member 20A (KIF20A) has been reported to be a promising immunotherapeutic target
      for pancreatic cancer. To investigate the expression of KIF20A in melanoma, we
      performed quantitative reverse transcript (RT)-PCR and western blotting analyses
      of melanoma cell lines. We also investigated primary melanomas and naevus tissues
      with immunohistochemistry and real-time RT-PCR. KIF20A expression was detected in
      59% of melanomas and 12% of naevi by immunohisto-chemistry, and 64% of melanomas
      and 60% of naevi by real-time RT-PCR. The primary melanomas that were positive
      for KIF20A showed a significantly greater thickness than those that were
      negative, and patients with KIF20A+ melanoma tended to develop recurrence
      earlier. These results suggest that immunotherapy with KIF20A may be a novel
      treatment option for advanced melanoma.

PMID- 22854761
TI  - Cerebral electromagnetic infraslow activity.

PMID- 22854762
TI  - Ictal onset baseline shifts and infraslow activity.
AB  - Ictal onset baseline shifts, in surface and intracranial EEG, have been shown to
      localize focal epilepsies. However, whether direct current EEG amplifiers are
      required to detect infraslow activity is unresolved. We retrospectively analyzed
      intracranial EEG data from 24 patients with temporal lobe seizures, who underwent
      long-term invasive EEG investigation and subsequent surgery. Data were recorded
      using a DeltaMed/Natus (Paris, France) system with Braintronics Brainbox EEG-1164
      (Almere, The Netherlands) with an input filter of 0.1 Hz. Visual comparison of
      infraslow activity with seizure activity in conventional frequency bands was
      performed using BESA software (Megis, Grafeling, Germany). Ictal onset baseline
      shifts were seen in 52 of 88 partial seizures and in all 11 secondarily
      generalized tonic-clonic seizures. They preceded ictal activity in conventional
      frequencies in some cases by several seconds. Topographical distribution was
      concordant with seizure onsets and distant sites with suspected involvement in
      seizure generation. It is concluded that ictal onset baseline shifts can be
      detected by commonly used EEG systems with an input filter of 0.1 Hz and may
      contribute to identify seizure onset and areas involved in seizure generation.

PMID- 22854763
TI  - Peri-ictal and interictal, intracranial infraslow activity.
AB  - It is widely assumed that the recording of EEG infraslow activity (ISA) requires
      direct current amplifiers. Yet, it has been shown during the past decade that
      conventional EEG systems can record activity between 0.01 and 0.1 Hz and that
      this frequency band contains additional information, especially in regard to
      seizure onset. To delineate the characteristics of background ISA, 24-hour scalp
      and intracranial recordings obtained from 5 patients during long-term monitoring
      were investigated. Scalp recordings had been sampled but intracranial tracings
      were continuous over periods of up to 3 days. Although scalp recordings were
      subject to artifact, intermittent genuine ISA increase could occur episodically
      in the interictal state not only distant from the ictal onset zone but also in
      the contralateral hemisphere. Intracranial recordings were limited, in this
      study, to portions of one hemisphere but likewise revealed that distant areas
      could show ISA increase lasting minutes or hours. This was at times not
      detectable when only the conventional frequency band was viewed. It is concluded
      that ISA information is contained in the clinical setting of intensive video
      monitoring studies for the detection of the epileptogenic zone and can provide
      additional information above and beyond what is seen in the conventional
      frequencies.

PMID- 22854764
TI  - Seizure localization using broadband EEG: comparison of conventional frequency
      activity, high-frequency oscillations, and infraslow activity.
AB  - In neocortical epilepsy, we showed that the seizure onset defined by ictal high
      frequency oscillations (HFO: >= 70 Hz) with subsequent evolution into slower
      frequency activity (i.e., HFOs+) was smaller in spatial distribution than that
      defined by conventional frequency activity (1-70 Hz), and that resection of HFO+
      areas resulted in favorable seizure outcome. This study further investigates
      ictal broadband EEG in the same cohort of patients by examining the infraslow
      activity, including ictal baseline ("direct current") shifts (IBS) and peri-ictal
      infraslow activity (0.02 to 0.2 Hz). The seizure onset zone had been defined and
      resected based on HFO+ by a prospectively defined protocol. We reviewed 11
      representative seizures from 6 patients by visual and spectral analyses using
      appropriate filters and timescales. The HFO seizure onset, in the high gamma or
      ripple frequency, preceded or followed the IBS closely (<300 ms). The IBS were
      negative or positive, ~1 mV in amplitude and 2 to 3 seconds long. Although the
      HFO+ were always ipsilateral to the surgical hemisphere, the IBS could be
      ipsilateral or contralateral. Compared with conventional frequency activity, the
      HFO+ and IBS were significantly smaller in spatial distribution and likely to be
      concordant. The peri-ictal infraslow activity consisted of distinct periodic or
      rhythmic (0.12 to 0.16 Hz) patterns, poorly concordant with IBS or HFO+. Although
      not statistically significant, better seizure outcome tended to correlate with
      smaller seizure onset zones and more complete resection of the HFO+ and IBS
      contacts. We conclude that IBS, like HFO+, define a smaller seizure onset zone
      and probably a more accurate epileptogenic zone in neocortical epilepsy.

PMID- 22854765
TI  - Slow brain activity (ISA/DC) detected by MEG.
AB  - Infraslow activity (ISA), direct coupled (DC), and direct current (DC) are the
      terms used to describe brain activity that occurs in frequencies below 0.1 Hz.
      Infraslow activity amplitude increase is also associated with epilepsy, traumatic
      brain injuries, strokes, tumors, and migraines and has been studied since the
      early 90s at the Henry Ford Hospital MEG Laboratory. We have used a DC-based
      magnetoencephalography (MEG) system to validate and characterize the ISA from
      animal models of cortical spreading depression thought to be the underlying
      mechanism of migraine and other cortical spreading depression-like events seen
      during ischemia, anoxia, and epilepsy. Magnetoencephalography characterizes these
      slow shifts easier than electroencephalography because there is no attenuation of
      these signals by the skull. In the current study, we report on ISA MEG signals of
      12 patients with epilepsy in the preictal and postictal states. In the minutes
      just before the onset of a seizure, large-amplitude ISA MEG waveforms were
      detected, signaling the onset of the seizure. It is suggested that MEG assessment
      of ISA, in addition to activity in the conventional frequency band, can at times
      be useful in the lateralization of epileptic seizures.

PMID- 22854766
TI  - Tangential and radial epileptic spike activity: different sensitivity in EEG and
      MEG.
AB  - OBJECTIVE: Observations in epileptic patients show that interictal spikes are
      sometimes only visible in electroencephalography (EEG) and sometimes only in
      magnetoencephalography (MEG). This observation cannot readily be explained by the
      theoretical sensitivities of EEG and MEG based on analytical models. In this
      context, we aimed to study the directional sensitivity of radial and tangential
      spike activity in numerical simulations using realistic head models. METHODS: We
      calculated the signal-to-noise ratio (SNR) of simulated spikes at varying
      orientations and with varying background activity in 12 brain regions in 4
      volunteers. Different levels of background activity were modeled by adjusting the
      amplitudes of several thousand dipoles distributed in the cortex. RESULTS: For a
      fixed realistic background activity, we found a higher SNR for MEG spikes for
      spike orientations that deviated not > 30 degrees  from the tangential direction.
      In contrast, we found a higher SNR for EEG spikes that deviated not > 45 degrees 
      from the radial direction. When the radial background activity was selectively
      increased, the sensitivity of EEG for radially oriented spikes decreased; when
      the tangential background activity selectively increased, the sensitivity of MEG
      for tangentially oriented spikes was decreased. CONCLUSIONS: Our simulations
      provide a possible explanation for the clinically observed differences in
      epileptic spike detection between EEG and MEG. Epileptic spike detection can be
      improved by analyzing a combination of EEG and MEG data.

PMID- 22854767
TI  - The utility of routine EEG in the diagnosis of sleep disordered breathing.
AB  - Sleep disordered breathing (SDB) is a common medical condition. Its
      manifestations of snoring, nocturnal choking, arousals, and sleep fragmentation
      can lead to excessive daytime sleepiness, neuropsychological slowing, lapses of
      consciousness, and accidents that can be misinterpreted as epileptic phenomena.
      Moreover, patients with documented epilepsy commonly exhibit similar
      symptomatology because of the undiagnosed coexistence of sleep apnea. Therefore,
      a large proportion of patients referred to the electroencephalogram (EEG)
      laboratory primarily to confirm or refute the diagnosis of epilepsy could suffer
      from latent sleep apnea and the routine EEG has the potential to divulge it. We
      retrospectively evaluated the reporting of sleep apnea symptomatology (snoring,
      choking, gasping/deep breath, apnea, desaturation, excessive drowsiness) in
      routine inpatient and outpatient adult EEG studies performed in our institution
      over the past 12 years (39,130 studies, approximately half of which recorded at
      least early stages of sleep). Comparisons were performed with the medical records
      to ascertain the coexistence of objectively diagnosed SDB with polysomnography
      before or after the EEG study and the importance of reporting variations in
      assisting with the diagnosis. Two illustrative examples are provided. Sixty-nine
      EEG studies were identified, performed primarily to confirm, or refute the
      diagnosis of epilepsy. The mean age of the subjects at EEG was 64 years (range 30
      89), and 55 (80%) were male. 36% of them suffered from known epilepsy. Snoring
      was the most commonly reported sign in 48 (70%) of the studies, followed by
      arousals in 29 (42%), apnea in 16 (23%), excessive drowsiness in 13 (19%),
      gasping/deep breath in 9 (13%), and desaturation in 7 (10%). A sleep disorder was
      suggested in 25 (36%) of the interpretations and a direct recommendation for a
      sleep study was made in 22 of them (32%). This interpretation was included in the
      impression of the report in 21 (30%) of the cases, in the detail in 20 (30%) of
      the cases and in both in 28 (40%). Only 14 (20%) patients underwent
      polysomnography, and all of them were formally diagnosed with SDB. Seven (50%) of
      them were diagnosed with obstructive sleep apnea, 2 (14%) with central sleep
      apnea, 3 (22%) with both, 1 (7%) with upper airways resistance syndrome, and 1
      (7%) with primary snoring. From these 14 patients, 9 (64%) were diagnosed with a
      sleep study performed after the EEG, 4 (29%) before the EEG interpretation, and 1
      (7%) had a repeat study after the EEG. In the logistic regression model applied,
      with the exception of the presence of arousals (odds ratio = 4.63, P = 0.033),
      none of the aforementioned symptomatology or the reporting of suspicion for SDB
      or the location (impression vs. detail) of the reporting showed a statistically
      significant association with the completion of a sleep study. Routine EEG offers
      a unique opportunity of direct clinical observation along with electrophysiologic
      and cardiorespiratory monitoring. When sleep is recorded, it can help identify
      clinical and electrographic features of sleep apnea and prompt confirmation with
      a polysomnogram in the appropriate clinical context. It can therefore serve as a
      valuable, adjunctive tool for the diagnosis of SDB. Our data highlight that
      potential but unveil its decreased use in the neurology community. Increased
      awareness is required by the EEG technologists, interpreting neurologists, and
      referring physicians, regarding reporting and using sleep apnea features on the
      EEG.

PMID- 22854768
TI  - Unmasking of periodic limb movements with the resolution of obstructive sleep
      apnea during continuous positive airway pressure application.
AB  - PURPOSE: Periodic limb movements (PLMs) and obstructive sleep apnea (OSA) may
      present as overlapping conditions. This study investigated the occurrence of PLM
      during continuous positive airway pressure (CPAP) titration, with the hypothesis
      that the presence of PLM during CPAP represented "unmasking" of a coexisting
      sleep disorder. METHODS: A total of 78 polysomnographic recordings in 39 OSA
      subjects with an hourly PLM index >=5 during CPAP application were evaluated.
      RESULTS: Application of CPAP significantly improved sleep architecture without
      change in the PLM index when compared with baseline. The PLM indices and PLM
      arousal indices were linearly correlated during both nights (r = 0.553, P < 0.01;
      r = 0.548, P < 0.01, respectively). Eleven subjects with low PLM indices at
      baseline had greater changes in the PLM index as compared with the sample
      remainder (P = 0.004). Sixteen subjects with significantly lower PLM indices at
      baseline required optimal CPAP levels higher than the sample average of 8.2 cm
      H2O (P = 0.032). These subjects also showed significantly higher median apnea
      hypopnea index (AHI) at baseline than the sample remainder (74.4 events per hour
      [range: 24.2-124.4 events per hour] vs. 22.7 events per hour [range: 8.6-77.4
      events per hour], respectively, P < 0.001). CONCLUSIONS: These findings suggest
      that PLM seen during CPAP titration may be related to a concurrent sleep disorder
      because of "unmasking" in patients with treated OSA.

PMID- 22854769
TI  - Electrophysiological characteristics of polyneuropathy in POEMS syndrome:
      comparison with CIDP.
AB  - OBJECTIVE: The purpose of this study was to evaluate the electrophysiological
      characteristics of polyneuropathy in POEMS syndrome. METHODS: A total 46 patients
      with POEMS syndrome and 46 patients with chronic inflammatory demyelinating
      polyneuropathy (CIDP) were included in this study. Six nerve conduction
      parameters including (1) motor conduction velocity, distal compound muscle action
      potential; (2) conduction block and temporal dispersion; (3) motor distal
      latency; (4) F wave; and (5) sensory conduction velocity were reviewed for the
      subjects in both POEMS and CIDP groups. RESULTS: The frequency of nerve
      unresponsiveness in the lower limbs of the POEMS group (motor responses were
      absent in 37.7% and sensory was absent in 41.7% of the patients) was higher than
      that of the CIDP group (motor responses were absent in 18.4% and sensory was
      absent in 24.4% of the patients). The peroneal motor conduction velocity was
      slowed, compound muscle action potential was lower, and distal latency was longer
      in POEMS groups than those in CIDP group. The percentage of prolonged distal
      compound muscle action potential duration, conduction velocities, distal
      latencies, and the absent F waves compatible with demyelination were
      significantly different between the two groups. Abnormal temporal dispersion was
      rarely seen, and conduction block was not observed in the patients with POEMS
      syndrome. CONCLUSIONS: The findings suggest that peroneal nerves are more
      severely involved, temporal dispersion of the distal compound muscle action
      potential and conduction block are less common, and there are less alterations of
      conduction (less demyelination) as evidenced by more normal distal latencies,
      conduction velocities, and F-wave latencies in POEMS syndrome. These features may
      be useful for the differentiation between POEMS syndrome and CIDP.

PMID- 22854770
TI  - Interval neurophysiological changes in non septic critically ill mechanically
      ventilated patients.
AB  - Peripheral nerve changes in critically ill patients are common, sepsis being the
      most important risk factor. The aim of our study is to investigate interval
      neurophysiological changes in non septic mechanically ventilated critically ill
      patients, a group who has not been the focus of previous studies. Consecutive non
      septic mechanically ventilated critically ill patients were included. Baseline
      nerve conduction studies (NCS) were done within 3 days of intensive care unit
      admission, and 48 hours after the initiation of mechanical ventilation, and were
      followed up 7-8 days later. Sural and ulnar sensory, and median and peroneal
      motor nerves were tested. Nine patients were studied, five (56%) showed
      significant changes in their NCS compared to baseline. The peroneal and sural
      nerve amplitudes significantly dropped in all of the five affected patients, with
      drop of those of the median motor nerves in two, and ulnar sensory nerves in
      three patients. In conclusion, interval changes in peripheral nerves can exist in
      critically ill mechanically ventilated non septic patients. The pattern is
      similar to critically ill patients with sepsis. Theories of possible
      pathophysiology of critical illness neuropathy should not merely depend on the
      presence of sepsis as a trigger and other mechanisms should be investigated.

PMID- 22854771
TI  - EEG in syncope:  useful or not?

PMID- 22854773
TI  - Economic evaluation of a participatory return-to-work intervention for temporary
      agency and unemployed workers sick-listed due to musculoskeletal disorders.
AB  - OBJECTIVES: The aim of the study was to evaluate the cost-effectiveness, 
      utility, and -benefit of a newly developed participatory return-to-work (RTW)
      program for temporary agency and unemployed workers, sick-listed due to
      musculoskeletal disorders. METHODS: An economic evaluation was conducted
      alongside a randomized controlled trial with a 12-month follow-up. Temporary
      agency and unemployed workers, sick-listed for 2a?"8 weeks due to musculoskeletal
      disorders, were randomized to the participatory RTW program (N=79) or usual care
      group (N=84). The new RTW program was aimed at making a consensus-based RTW
      action plan with the possibility of a temporary (therapeutic) workplace. Effect
      outcomes were sustainable RTW and quality-adjusted life years (QALY). Healthcare
      utilization was measured from the social insurera?TMs perspective and societal
      perspective. RESULTS: Total healthcare costs in the participatory RTW program
      group [10 189 (standard deviation [SD] 7055) euros] were statistically
      significantly higher compared to care-as-usual [7862 (SD 7394) euros]. The cost
      effectiveness analyses showed that the new intervention was more effective but
      also more costly than usual care (ie, to gain RTW one day earlier in the
      participatory RTW program group approximately 80 euros needed to be invested).
      The net societal benefit of the participatory RTW program compared to care-as
      usual was 2073 euros per worker. CONCLUSIONS: The newly developed participatory
      RTW program was more effective but also more costly than usual care. The program
      enhanced work resumption and generated a net socioeconomic benefit. Hence,
      implementation of the participatory RTW program may have potential to achieve a
      sustainable contribution of vulnerable workers to the labor force.

PMID- 22854777
TI  - Defining the mode of tumour growth by clonal analysis.
AB  - Recent studies using the isolation of a subpopulation of tumour cells followed by
      their transplantation into immunodeficient mice provide evidence that certain
      tumours, including squamous skin tumours, contain cells with high clonogenic
      potential that have been referred to as cancer stem cells (CSCs). Until now, CSC
      properties have only been investigated by transplantation assays, and their
      existence in unperturbed tumour growth is unproven. Here we make use of clonal
      analysis of squamous skin tumours using genetic lineage tracing to unravel the
      mode of tumour growth in vivo in its native environment. To this end, we used a
      genetic labelling strategy that allows individual tumour cells to be marked and
      traced over time at different stages of tumour progression. Surprisingly, we
      found that the majority of labelled tumour cells in benign papilloma have only
      limited proliferative potential, whereas a fraction has the capacity to persist
      long term, giving rise to progeny that occupy a significant part of the tumour.
      As well as confirming the presence of two distinct proliferative cell
      compartments within the papilloma, mirroring the composition, hierarchy and fate
      behaviour of normal tissue, quantitative analysis of clonal fate data indicates
      that the more persistent population has stem-cell-like characteristics and cycles
      twice per day, whereas the second represents a slower cycling transient
      population that gives rise to terminally differentiated tumour cells. Such
      behaviour is shown to be consistent with double-labelling experiments and
      detailed clonal fate characteristics. By contrast, measurements of clone size and
      proliferative potential in invasive squamous cell carcinoma show a different
      pattern of behaviour, consistent with geometric expansion of a single CSC
      population with limited potential for terminal differentiation. This study
      presents the first experimental evidence for the existence of CSCs during
      unperturbed solid tumour growth.

PMID- 22854778
TI  - A III-V nanowire channel on silicon for high-performance vertical transistors.
AB  - Silicon transistors are expected to have new gate architectures, channel
      materials and switching mechanisms in ten years' time. The trend in transistor
      scaling has already led to a change in gate structure from two dimensions to
      three, used in fin field-effect transistors, to avoid problems inherent in
      miniaturization such as high off-state leakage current and the short-channel
      effect. At present, planar and fin architectures using III-V materials,
      specifically InGaAs, are being explored as alternative fast channels on silicon
      because of their high electron mobility and high-quality interface with gate
      dielectrics. The idea of surrounding-gate transistors, in which the gate is
      wrapped around a nanowire channel to provide the best possible electrostatic gate
      control, using InGaAs channels on silicon, however, has been less well
      investigated because of difficulties in integrating free-standing InGaAs
      nanostructures on silicon. Here we report the position-controlled growth of
      vertical InGaAs nanowires on silicon without any buffering technique and
      demonstrate surrounding-gate transistors using InGaAs nanowires and
      InGaAs/InP/InAlAs/InGaAs core-multishell nanowires as channels. Surrounding-gate
      transistors using core-multishell nanowire channels with a six-sided, high
      electron-mobility transistor structure greatly enhance the on-state current and
      transconductance while keeping good gate controllability. These devices provide a
      route to making vertically oriented transistors for the next generation of field
      effect transistors and may be useful as building blocks for wireless networks on
      silicon platforms.

PMID- 22854780
TI  - HIV-infected T cells are migratory vehicles for viral dissemination.
AB  - After host entry through mucosal surfaces, human immunodeficiency virus-1 (HIV-1)
      disseminates to lymphoid tissues to establish a generalized infection of the
      immune system. The mechanisms by which this virus spreads among permissive target
      cells locally during the early stages of transmission and systemically during
      subsequent dissemination are not known. In vitro studies suggest that the
      formation of virological synapses during stable contacts between infected and
      uninfected T cells greatly increases the efficiency of viral transfer. It is
      unclear, however, whether T-cell contacts are sufficiently stable in vivo to
      allow for functional synapse formation under the conditions of perpetual cell
      motility in epithelial and lymphoid tissues. Here, using multiphoton intravital
      microscopy, we examine the dynamic behaviour of HIV-infected T cells in the lymph
      nodes of humanized mice. We find that most productively infected T cells migrate
      robustly, resulting in their even distribution throughout the lymph node cortex.
      A subset of infected cells formed multinucleated syncytia through HIV envelope
      dependent cell fusion. Both uncoordinated motility of syncytia and adhesion to
      CD4(+) lymph node cells led to the formation of long membrane tethers, increasing
      cell lengths to up to ten times that of migrating uninfected T cells. Blocking
      the egress of migratory T cells from the lymph nodes into efferent lymph vessels,
      and thus interrupting T-cell recirculation, limited HIV dissemination and
      strongly reduced plasma viraemia. Thus, we have found that HIV-infected T cells
      are motile, form syncytia and establish tethering interactions that may
      facilitate cell-to-cell transmission through virological synapses. Migration of T
      cells in lymph nodes therefore spreads infection locally, whereas their
      recirculation through tissues is important for efficient systemic viral spread,
      suggesting new molecular targets to antagonize HIV infection.

PMID- 22854781
TI  - A restricted cell population propagates glioblastoma growth after chemotherapy.
AB  - Glioblastoma multiforme is the most common primary malignant brain tumour, with a
      median survival of about one year. This poor prognosis is due to therapeutic
      resistance and tumour recurrence after surgical removal. Precisely how recurrence
      occurs is unknown. Using a genetically engineered mouse model of glioma, here we
      identify a subset of endogenous tumour cells that are the source of new tumour
      cells after the drug temozolomide (TMZ) is administered to transiently arrest
      tumour growth. A nestin-DeltaTK-IRES-GFP (Nes-DeltaTK-GFP) transgene that labels
      quiescent subventricular zone adult neural stem cells also labels a subset of
      endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ,
      pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating
      with the Nes-DeltaTK-GFP transgene subpopulation. Ablation of the GFP+ cells with
      chronic ganciclovir administration significantly arrested tumour growth, and
      combined TMZ and ganciclovir treatment impeded tumour development. Thus, a
      relatively quiescent subset of endogenous glioma cells, with properties similar
      to those proposed for cancer stem cells, is responsible for sustaining long-term
      tumour growth through the production of transient populations of highly
      proliferative cells.

PMID- 22854783
TI  - Pericarditis: sometimes an autoinflammatory disease?

PMID- 22854782
TI  - Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular
      synapses.
AB  - Motor axons receive retrograde signals from skeletal muscle that are essential
      for the differentiation and stabilization of motor nerve terminals.
      Identification of these retrograde signals has proved elusive, but their
      production by muscle depends on the receptor tyrosine kinase, MuSK (muscle,
      skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein
      receptor (LDLR)-related protein 4), an LDLR family member that forms a complex
      with MuSK, binds neural agrin and stimulates MuSK kinase activity. Here we show
      that Lrp4 also functions as a direct muscle-derived retrograde signal for early
      steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary,
      independent of MuSK activation, for presynaptic differentiation in vivo, and we
      show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle
      and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse
      formation by binding agrin, activating MuSK and stimulating postsynaptic
      differentiation, and functioning in turn as a muscle-derived retrograde signal
      that is necessary and sufficient for presynaptic differentiation.

PMID- 22854784
TI  - Fish oil for attenuating posttraumatic stress symptoms among rescue workers after
      the great east Japan earthquake: a randomized controlled trial.

PMID- 22854785
TI  - Assessing the combined effects of urbanisation and climate change on the river
      water quality in an integrated urban wastewater system in the UK.
AB  - Climate change and urbanisation are key factors affecting the future of water
      quality and quantity in urbanised catchments and are associated with significant
      uncertainty. The work reported in this paper is an evaluation of the combined and
      relative impacts of climate change and urbanisation on the receiving water
      quality in the context of an Integrated Urban Wastewater System (IUWS) in the UK.
      The impacts of intervening system operational control parameters are also
      investigated. Impact is determined by a detailed modelling study using both local
      and global sensitivity analysis methods together with correlation analysis. The
      results obtained from the case-study analysed clearly demonstrate that climate
      change combined with increasing urbanisation is likely to lead to worsening river
      water quality in terms of both frequency and magnitude of breaching threshold
      dissolved oxygen and ammonium concentrations. The results obtained also reveal
      the key climate change and urbanisation parameters that have the largest negative
      impact as well as the most responsive IUWS operational control parameters
      including major dependencies between all these parameters. This information can
      be further utilised to adapt future IUWS operation and/or design which, in turn,
      should make these systems more resilient to future climate and urbanisation
      changes.

PMID- 22854786
TI  - Osteonecrosis of the femoral head in a patient with Henoch-Schonlein purpura and
      drug-induced hypersensitivity syndrome treated with corticosteroids.

PMID- 22854788
TI  - He loves her, he loves her not: attachment style as a personality antecedent to
      men's ambivalent sexism.
AB  - The authors present an integrative account of how attachment insecurities relate
      to sexism. Two studies showed that attachment avoidance predisposes men to
      endorse hostile but to reject benevolent sexism (BS), whereas attachment anxiety
      predisposes men toward ambivalent (both hostile and benevolent) sexism. The
      authors also tested predicted mediators, finding that men's social dominance
      orientation (a competitive intergroup ideology) mediated the avoidance to hostile
      sexism link. In addition, romanticism (an idealized interpersonal ideology)
      mediated attachment insecurity to BS links: (a) Avoidant men tended to reject
      romanticism (i.e., were cynical about romance) and, in turn, were likely to
      reject BS, whereas (b) anxious men tended to endorse romanticism (i.e., were
      idealistic about romance) and, in turn, likely to endorse BS. The authors
      conclude that men's sexism stems in part from dispositional attachment working
      models, both directly and through the interpersonal and intergroup ideologies
      they generate.

PMID- 22854789
TI  - The role of self-image concerns in discrepancies between implicit and explicit
      self-esteem.
AB  - Four experiments examined the hypothesis that individuals who hold discrepant
      implicit and explicit self-esteem possess relatively strong self-image concerns.
      As a result, they may act irrationally when expressing sexual health attitudes.
      In support of the hypothesis, Experiments 1a and 1b demonstrate that large self
      esteem discrepancy participants possess strong implicit self-image ambivalence
      relative to small self-esteem discrepancy participants. In Experiments 2 and 3,
      participants who varied in self-esteem discrepancies received either negative or
      positive (or no) feedback on an intelligence test, and then they were given an
      opportunity to express implicit and explicit attitudes toward condoms. Large self
      esteem discrepancy participants who received a self-threat responded irrationally
      and expressed relatively strong negative implicit (but not explicit) attitudes
      toward condoms. However, this detrimental effect was completely reversed
      following a self-affirmation to large discrepancy participants. The implicit and
      explicit attitudes toward condoms of small discrepancy participants were
      unaffected by a self-threat or a self-affirmation.

PMID- 22854790
TI  - Whether, when, and how is spirituality related to well-being? Moving beyond
      single occasion questionnaires to understanding daily process.
AB  - Prior research suggests that spirituality is positively related to well-being.
      Nevertheless, within-person variability in spirituality has yet to be addressed.
      Do people experience greater spirituality on some days versus others? Does daily
      spirituality predict daily well-being? Do within-person relationships between
      spirituality and well-being vary as a function of trait spirituality? The authors
      examined such questions using a daily diary study with 87 participants who
      provided reports of their daily spirituality and well-being for a total of 1,239
      days. They found that daily spirituality was positively related to meaning in
      life, self-esteem, and positive affect, and the link from daily spirituality to
      both self-esteem and positive affect was fully mediated by meaning in life.
      Moreover, within-person relationships between daily spirituality and self-esteem
      and meaning in life were stronger for people higher in trait spirituality. Lagged
      analyses found positive relationships between present day spirituality and next
      day's meaning in life; there was no evidence for meaning in life as a predictor
      of the next day's spirituality. When focusing on affect, for people higher in
      trait spirituality, greater negative affect (and lower positive affect) predicted
      greater spirituality the next day. These results provide new insights into how
      spirituality operates as a fluctuating experience in daily life.

PMID- 22854787
TI  - Chemoenzymatic synthesis of cholesteryl-6-O-tetradecanoyl-alpha-D
      glucopyranoside: a product of host cholesterol efflux promoted by Helicobacter
      pylori.
AB  - In a three-step protocol involving regioselective enzymatic acylation, per-O
      trimethylsilylation, and a one-pot alpha-glycosidation-deprotection sequence,
      cholesteryl-6-O-tetradecanoyl-alpha-D-glucopyranoside (alpha-CAG) of Helicobacter
      pylori is afforded starting from glucose in an overall yield of 45%. The
      production of CAG can be scaled to make purified quantities available to the
      biological community for the first time.

PMID- 22854791
TI  - Dispositional anxiety blocks the psychological effects of power.
AB  - A growing body of research demonstrates that power promotes a fundamental
      orientation toward approach and agency. The current studies suggest that this
      tendency is moderated by dispositional anxiety. In two experiments, high levels
      of dispositional anxiety blocked the psychological effects of power. Although
      people low in anxiety responded to a power prime with greater willingness to take
      risks, those high in anxiety did not (Experiment 1). Similarly, whereas those low
      in social anxiety responded to power with increased sexual attraction toward a
      confederate, individuals high in social anxiety failed to show the same effect
      (Experiment 2). In both studies, the interaction between power and anxiety was
      statistically mediated by perceptions of reward. Although power enhanced people's
      perceptions of reward, this effect was eliminated by high levels of dispositional
      anxiety. This research provides insight into how, and in whom, power promotes
      approach and agentic behavior.

PMID- 22854792
TI  - Are implicit motives the need to feel certain affect? Motive-affect congruence
      predicts relationship satisfaction.
AB  - The authors test the assumption that the core of implicit motives is the desire
      for particular affective experiences and that motive satisfaction need not be
      tied to any particular domain. Using the context of romantic relationships, cross
      sectional Study 1 and experimental Study 2 showed that people with a high
      affiliation motive were more satisfied when they experienced more affiliation
      specific affect (calmness and relaxation). However, people with a higher power
      motive were more satisfied in their relationships when they experienced more
      power-specific affect (strength and excitement) in these relationships. The
      results support the idea that an implicit motive involves the desire for specific
      affective experiences and that frequent experiences of one's preferred affect can
      lead to enhanced satisfaction and well-being in a domain, even one that is not
      typically associated with that motive.

PMID- 22854793
TI  - Measuring environmental barriers faced by individuals living with stroke:
      development and validation of the Chinese version of the Craig Hospital Inventory
      of Environmental Factors.
AB  - OBJECTIVE: To develop and validate a Chinese version of the Craig Hospital
      Inventory of Environmental Factors. DESIGN: Descriptive case-series. SUBJECTS: A
      total of 107 individuals with chronic stroke and 56 age-matched healthy subjects.
      METHODS: The English version of the 25-item Craig Hospital Inventory of
      Environmental Factors was translated into Chinese using standardized procedures,
      and then administered to both the stroke and control groups. The same
      questionnaire was administered again to the stroke group 1-2 weeks after the
      first session. RESULTS: The Craig Hospital Inventory of Environmental Factors had
      good internal consistency (Cronbach's alpha = 0.916) and test-retest reliability
      (intra-class correlation coefficient = 0.845). It also had significant
      association with Personal Wellbeing Index (r(s) = -0.379, p = 0.001) but not with
      Fugl-Meyer Assessment upper limb (r(s) = -0.107, p = 0.320) and lower limb motor
      scores (r(s) = -0.032, p = 0.768) among stroke subjects, thus demonstrating
      convergent and discriminant validity, respectively. The mean Craig Hospital
      Inventory of Environmental Factors score in the stroke group was also
      significantly higher than that in controls (p = 0.020), thus showing good known
      groups validity. CONCLUSION: The Chinese version of the Craig Hospital Inventory
      of Environmental Factors is a reliable and valid tool for evaluating the
      perceived environmental barriers experienced by people with chronic stroke.

PMID- 22854794
TI  - Can roads be used as transects for primate population surveys?.
AB  - Line transect distance sampling (LTDS) can be applied to either trails or roads.
      However, it is likely that sampling along roads might result in biased density
      estimates. In this paper, we compared the results obtained with LTDS applied on
      trails and roads for two primate species (Callithrix penicillata and Callicebus
      nigrifrons) to clarify whether roads are appropriate transects to estimate
      densities. We performed standard LTDS surveys in two nature reserves in south
      eastern Brazil. Effective strip width and population density were different
      between trails and roads for C. penicillata, but not for C. nigrifrons. The
      results suggest that roads are not appropriate for use as transects in primate
      surveys, at least for some species. Further work is required to fully understand
      this issue, but in the meantime we recommend that researchers avoid using roads
      as transects or treat roads and trails as covariates when sampling on roads is
      unavoidable.

PMID- 22854799
TI  - Stepwise assembly of homochiral coordination polymers based on the precursor of
      an enantiopure Yb3Mn6 cluster.
AB  - Two homochiral coordination polymers, namely, [Yb(III)(3)Mn(III)(6)(L)(6)(MU(2)
      OMe)(6)(isonicotinate)(2)(HOMe)(2)][Yb(III)(3)Mn(III)(6)(L)(6)(MU(2)
      OMe)(6)(isonicotinate)(2)(HOMe)(4)](NO(3))(2).6MeOH.12H(2)O (5) (H(3)L = (S,E)-4
      (2-hydroxybenzylideneamino)-2-hydroxybutanoic acid) and
      [Yb(III)(3)Mn(III)(6)Na(L)(6)(MU(2)-OMe)(6)(OOCH)(3)]I.17H(2)O (6), have been
      constructed by utilizing a stable enantiopure [Yb(III)(3)Mn(III)(6)(L)(6)(MU(2)
      OMe)(6)](3+) (Yb(3)Mn(6)) cluster as a precursor.

PMID- 22854803
TI  - Serum anti-lysosomal-associated membrane protein-2 antibody levels in cutaneous
      polyarteritis nodosa.
AB  - Lysosomal-associated membrane protein-2 (LAMP-2) is a target antigen for anti
      neutrophil cytoplasmic antibodies (ANCAs), which are closely linked to a subset
      of primary systemic vasculitides. Cutaneous polyarteritis nodosa (CPN) is a
      necrotizing vasculitis of small to medium-sized arteries within the skin. We
      measured levels of serum anti-LAMP-2 antibody in 50 patients with CPN, 8 with
      microscopic polyangiitis (MPA), and 34 healthy persons. We also investigated the
      presence of ANCA in patients with CPN using indirect immunofluorescence (IIF), a
      direct ELISA and a capture ELISA specific for myeloperoxidase (MPO) and
      proteinase 3 (PR3). Serum anti-LAMP-2 antibody levels differed significantly
      between patients with CPN (0.263 U/ml) and those with MPA (0.180 U/ml) (p =
      0.0102). Serum of all patients with CPN was negative for MPO-ANCA and PR3-ANCA by
      both direct ELISA and capture ELISA. In contrast, IIF assay revealed ANCA in 42
      (84.0%) of the 50 CPN patients. Serum anti-LAMP-2 antibody levels in the
      perinuclear ANCA (P-ANCA) group were significantly elevated compared with the non
      ANCA group (p = 0.0147). We suggest that anti-LAMP-2 antibody could play an
      important role in the pathogenesis of CPN in the presence of P-ANCA detected by
      IIF.

PMID- 22854804
TI  - Robot-aided gait training in an individual with chronic spinal cord injury:  a
      case study.
AB  - BACKGROUND AND PURPOSE: Traditional physical therapy is beneficial in restoring
      mobility in individuals who have sustained spinal cord injury (SCI), but residual
      limitations often persist. Robotic technologies may offer opportunities for
      further gains. The purpose of this case study was to document the use and
      practicality of gait training for an individual with chronic, incomplete SCI with
      asymmetric lower limb motor deficits using a novel robotic knee orthosis (RKO).
      CASE DESCRIPTION: The participant was a 22-year-old woman who sustained fractures
      of the odontoid process and C5-C6 vertebrae from a motor vehicle accident
      resulting in incomplete SCI with asymmetric tetraparesis, right side more severe
      than left side. She required supervised assistance with gait and balance tasks,
      minimal assistance to ascend/descend steps using a handrail, and upper extremity
      assistance for sit-to-stand tasks. INTERVENTION: The participant underwent 7 one
      hour sessions of mobility training, using a novel RKO. Her primary goal was to
      increase independence and endurance with mobility. OUTCOMES: Functional measures
      included the 6-Minute Walk Test, the Berg Balance Scale, the Timed Up & Go Test,
      and the 10-Meter Walk Test. Outcomes were assessed and recorded at baseline and
      on completion of 7 hours of training with the device over a 2-week period. No
      adverse events occurred. The RKO was well received by both the participant and
      the treating therapist. The participant demonstrated improvements in the 6-Minute
      Walk Test and Berg Balance Scale after RKO-training intervention. DISCUSSION:
      Outcomes suggest that the use of this device during a physical therapy program
      for an individual with incomplete SCI is practical and this device may be a
      useful adjunct to standard training.

PMID- 22854805
TI  - The World Health Organization Disability Assessment Scale, WHODAS II: reliability
      and validity in the measurement of activity and participation in a spinal cord
      injury population.
AB  - OBJECTIVE: To evaluate the reliability and validity of WHODAS II within the
      spinal cord injury population. SUBJECTS: Sixty-three people with traumatic spinal
      cord injury. METHODS: The World Health Organization Disability Assessment Scale
      II (WHODAS II), Craig Handicap Assessment and Reporting Technique, and Medical
      Outcomes Study 36-item Short-Form Health Survey (MOS SF-36) were administered at
      2 years post discharge from rehabilitation. Distribution, reliability,
      discriminant validity, and convergent/divergent validity were evaluated using
      classical tests. Rasch analyses were applied to assess dimensionality, item
      spread, and person/item reliability. RESULTS: Cronbach's alpha coefficients
      ranged from 0.61 (getting around) to 0.97 (participation). Ceiling effects were
      present in 4 out of 6 domains. WHODAS II discriminated between levels of
      impairment and work force status on 'self-care', 'getting around', 'life
      activities', and total score. Correlations with MOS SF-36 supported
      convergent/divergent validity. Five items didn't fit the Rasch model. The
      item/person map reveald a shortage of items able to differentiate the more able
      person. WHODAS II demonstrated good person and item separation and reliability.
      CONCLUSION: This study provides preliminary support for reliability and validity
      of WHODAS II in a spinal cord injured population. Limitations were noted for
      dimensionality and item person distribution. Findings need to be confirmed in
      larger samples.

PMID- 22854807
TI  - Rapid thermally assisted donor-acceptor catenation.
AB  - Charged donor-acceptor [2]catenanes containing cyclobis(paraquat-p-phenylene) as
      the ring component can be synthesised in yields of up to 88% in under one hour by
      heating two precursors in the presence of macrocyclic polyether templates in N,N
      dimethylformamide at 80  degrees C.

PMID- 22854806
TI  - Characterization of short white matter fiber bundles in the central area from
      diffusion tensor MRI.
AB  - INTRODUCTION: Diffusion tensor imaging and tractography allow studying white
      matter fiber bundles in the human brain in vivo. Electrophysiological studies and
      postmortem dissections permit improving our knowledge about the short association
      fibers connecting the pre- and postcentral gyri. The aim of this study was first
      to extract and analyze the features of these short fiber bundles and secondly to
      analyze their asymmetry according to the subjects' handedness. METHODS: Ten right
      handed and ten left-handed healthy subjects were included. White matter fiber
      bundles were extracted using a streamline tractography approach, with two seed
      regions of interest (ROI) taken from a parcellation of the pre- and postcentral
      gyri. This parcellation was achieved using T1 magnetic resonance images (MRI) and
      semi-automatically generated three ROIs within each gyrus. MRI tracks were
      reconstructed between all pairs of ROIs connecting the adjacent pre- and
      postcentral gyri. A quantitative analysis was performed on the number of tracks
      connecting each ROI pair. A statistical analysis studied the repartition of these
      MRI tracks in the right and left hemispheres and as a function of the subjects'
      handedness. RESULTS: The quantitative analysis showed an increased density of MRI
      tracks in the middle part of the central area in each hemisphere of the 20
      subjects. The statistical analysis showed significantly more MRI tracks for the
      left hemisphere, when we consider the whole population, and this difference was
      presumably driven by the left-handers. CONCLUSION: These results raise questions
      about the functional role of these MRI tracks and their relation with laterality.

PMID- 22854808
TI  - The data deluge.

PMID- 22854809
TI  - Finding CDK: linking yeast with humans.

PMID- 22854810
TI  - Classifying collective cancer cell invasion.
AB  - Most invasive solid tumours display predominantly collective invasion, in which
      groups of cells invade the peritumoral stroma while maintaining cell-cell
      contacts. As the concepts and experimental models for functional analysis of
      collective cancer cell invasion are rapidly developing, we propose a framework
      for addressing potential mechanisms, experimental strategies and technical
      challenges to study this process.

PMID- 22854811
TI  - Nuanced junctional RhoA activity.
AB  - RhoA signalling controls many diverse cellular processes, and thus discovering
      the mechanisms that determine its specific outcomes is a tantalizing challenge. A
      previously uncharacterized regulatory module operates selectively at the zonula
      adherens of epithelial cell junctions, in which positive and negative RhoA
      regulators are coordinated to fine-tune RhoA activity.

PMID- 22854812
TI  - FOXOphagy path to inducing stress resistance and cell survival.
AB  - Nutrient deprivation and other stress stimuli elicit metabolic changes (such as
      the induction of autophagy and activation of FOXO transcription factors) that
      help an organism adapt to stressful conditions. A link between these stress
      response pathways is revealed by the finding that FOXO3 upregulates the
      expression of glutamine synthetase to promote glutamine accumulation, inhibit
      mTOR signalling and promote autophagy.

PMID- 22854813
TI  - Brassinosteroids, gibberellins and light-mediated signalling are the three-way
      controls of plant sprouting.
AB  - The steroid hormones found in plants, the brassinosteroids, were originally
      genetically identified about 15 years ago as critical regulators of seedling
      photomorphogenesis. Two studies now shed light on the molecular mechanisms behind
      this observation. Brassinosteroids control seedling morphogenesis through direct
      interaction with master transcriptional regulators downstream of growth-promoting
      hormones and light signalling.

PMID- 22854814
TI  - Seeing the Warburg effect in the developing retina.
AB  - Proliferating cells of the Xenopus laevis retina facultatively use aerobic
      glycolysis instead of oxidative phosphorylation. This demonstrates that the
      metabolic rewiring usually associated with the Warburg effect in tumorigenesis
      may be a more widespread feature of proliferative metabolism than generally
      appreciated.

PMID- 22854821
TI  - A rosette cooling cell: more effective container for solubilization of single
      walled carbon nanotubes under probe-type ultrasonic irradiation.
AB  - Probe-type ultrasonication has been employed for surfactant-aided solubilization,
      or individualization, of single-walled carbon nanotubes (SWNTs). The resulting
      solution can be used not only for spectroscopic analyses such as absorption,
      photoluminescence, and circular dichroism, but also for separation by density
      gradient ultracentrifugation, dielectrophoresis, chromatography, and polymer
      wrapping. In spite of its importance, the sonochemical processing of SWNTs has
      not been considered seriously. Herein, we report on a more efficient cooling cell
      for probe-type ultrasonication. As compared with a conventional cylindrical cell,
      the concentration of the SWNTs solubilized in water was found to be almost double
      in a rosette cooling cell after ultracentrifugation. The efficiency of a rosette
      cell can be attributed to the higher efficiency in circulation and cooling of the
      SWNT dispersion as well as enhancement of the cavitation process.

PMID- 22854822
TI  - Block copolymer assisted synthesis of porous alpha-Ni(OH)2 microflowers with high
      surface areas as electrochemical pseudocapacitor materials.
AB  - Porous alpha-Ni(OH)(2) microflowers are successfully synthesized via a one-step
      aqueous-phase reaction assisted by block copolymers under mild conditions. The
      electrochemical measurement demonstrates that the alpha-Ni(OH)(2) microflowers
      calcined at 200  degrees C are capable to deliver a specific capacity of 1551 F
      g(-1) in 6 M KOH solution, suggesting their high potential as a novel
      electrochemical pseudocapacitor.

PMID- 22854823
TI  - Prevalence of history of childhood sexual abuse in consecutive hospital
      admissions of women with psychotic diagnosis in Israel: a preliminary report.

PMID- 22854824
TI  - [Sport for pacemaker patients].
AB  - Sport activity is an important issue in many patients with a pacemaker either
      because they performed sport activities before pacemaker implantation to reduce
      the cardiovascular risk or to improve the course of an underlying cardiovascular
      disease (e.g. coronary artery disease, heart failure) by sports. Compared to
      patients with an implantable cardioverter defibrillator (ICD) the risks from
      underlying cardiovascular disease (e.g. ischemia, heart failure), arrhythmia,
      lead dysfunction or inappropriate therapy are less important or absent. Sport is
      contraindicated in dyspnea at rest, acute heart failure, new complex arrhythmia,
      acute myocarditis and acute myocardial infarction, valvular disease with
      indications for intervention and surgery and comorbidities which prevent physical
      activity. Patients with underlying cardiovascular disease (including
      hypertension) should preferably perform types and levels of physical activity
      that are aerobic (with dynamic exercise) such as running, swimming, cycling
      instead of sport with high anaerobic demands and high muscular workload. In heart
      failure, studies demonstrated advantages of isometric sport that increases the
      amount of muscle, thereby preventing cardiac cachexia. Sport with a risk of blows
      to the chest or physical contact (e.g. boxing, rugby, martial arts) should be
      avoided. Implantation, programming and follow-up should respect specific
      precautions to allow optimal physical activity with a pacemaker including
      implantation of bipolar leads on the side contralateral to the dominant hand,
      individual programming of the upper sensor and tracking rate and regular exercise
      testing.

PMID- 22854825
TI  - The right heart in athletes. Do we really have sufficient evidence for exercise
      induced arrhythmogenic right ventricular cardiomyopathy?

PMID- 22854826
TI  - Characterization of metalloanticancer capacity of an agglutinin from wheat.
AB  - Many anticancer drugs cannot recognize selectively tumor tissues, and cause
      destruction to normal ones. Although it is very toxic, cisplatin is still one of
      the most applied chemotherapeutics used for treatment of sarcomas, carcinomas,
      etc. It causes severe side effects as a result of the lack of selectivity of the
      drug to tumor tissue and acquired or intrinsic resistance occurs. Wheat germ
      agglutinin (WGA) is a lectin that specifically recognizes transformed cells:
      prostate cancer cells, pancreatic cells etc., and is uptaken into the tumor cells
      for which it appears to be a suitable target for anticancer agents. A
      fluorescence spectroscopy method was used to study the interaction of WGA with
      four metal-based anticancer drugs: cisplatin, Pt porphyrin and two gold
      porphyrins. The affinity constant (k(D)) for binding of cisplatin with WGA was
      k(D) = 6.67 +/- 2.5 MUM. The hyperbolic curve indicated the presence of a single
      cisplatin binding site. The affinity of Au and Pt porphyrin to WGA (k(D) = 0.08
      0.49 MUM) is almost two orders of magnitude higher than that for cisplatin. We
      found that Pt porphyrin could displace fluorescent dye ANS showing an increase in
      the fluorescence intensity with a concomitant blue shift of the emission maximum
      suggesting that the compounds accommodate the same binding site. Current research
      characterizes the metalloanticancer binding capacity of WGA. Our results indicate
      that four metal-based anticancer agents have high affinity for WGA. Since WGA
      recognizes transformed cells, the obtained data show that this protein might have
      putative usage as a drug delivery molecule in cancer.

PMID- 22854827
TI  - Bottom-up synthesis of coordination polymers based on carborane backbones and
      Cu2(CO2)4 paddle-wheel: ligand metathesis with metallotecons.
AB  - Reported here are the bottom-up synthesis and structural analysis as well as the
      adsorption property investigation of a series of isostructural metal-organic
      frameworks based on carborane backbones and Cu(2)(CO(2))(4) units. All these
      compounds are 2D grid structures composed of four component rings. Using linear p
      CDC (p-CDCH(2) = 1,12-dihydroxycarbonyl-1,12-dicarba-closo-dodecaborane) as a
      backbone, only one type of ring formed. However, five types of rings may exist
      when m-CDCH(2) (m-CDCH(2) = 1,7-dihydroxycarbonyl-1,7-dicarba-closo-dodecaborane)
      was used due to its varied orientation. Here, the solvent molecules play a key
      role in the formation of these compounds and the expected five types of rings
      were obtained. The gas sorption properties of compounds 5' and 8' were studied.
      These frameworks preferentially adsorb CO(2) over both CH(4) and N(2) due to the
      coordinatively unsaturated copper ions.

PMID- 22854829
TI  - Patient recovery expectations in non-chronic non-specific low back pain: a
      qualitative investigation.
AB  - OBJECTIVE: Low recovery expectations have been identified as a strong and
      consistent predictor of poor outcome in non-chronic non-specific low back pain
      (NSLBP). The aim of this study was to explore how people determine their own
      recovery expectation during an episode of non-chronic NSLBP. SUBJECTS AND
      METHODS: In-depth interviews were conducted with a purposive sample of people
      with non-chronic NSLBP and low recovery expectations. Interviews were audio-
      recorded and transcribed verbatim. Two researchers independently applied open
      coding, followed by axial coding to allow themes to emerge from the data using a
      constant comparison method. RESULTS: The central theme of the person and 4
      subthemes of pain, progress, performance, and treatment emerged from the data.
      The formation of recovery expectations was dependent on the person's unique
      apprasial of their pain, how the condition had progressed, the limitation of
      their performance of activities, and the impact of different aspects of
      treatment. CONCLUSION: Recovery expectation is a person's appraisal of several
      factors to determine when they are likely to return to their usual activities
      during an episode of non-chronic NSLBP. Health professionals should explore the
      person's perception of these factors as part of a tailored intervention to
      prevent non-chronic NSLBP progressing to chronic NSLBP.

PMID- 22854828
TI  - MiR-30e and miR-181d control radial glia cell proliferation via HtrA1 modulation.
AB  - The precise mechanisms by which microRNAs (miRNAs) contribute to the dynamic
      regulation of gene expression during the forebrain development are still partly
      elusive. Here we show that the depletion of miRNAs in the cerebral cortex and
      hippocampus, via genetic inactivation of Dicer after the onset of forebrain
      neurogenesis, profoundly impairs the morphological and proliferative
      characteristics of neural stem and progenitor cells. The cytoarchitecture and
      self-renewal potential of radial glial (RG) cells located within the cerebral
      cortex and the hippocampus were profoundly altered, thus causing a significant
      derangement of both the post natal dorsal sub-ventricular zone and the dentate
      gyrus. This effect was attributed to the High-temperature requirement A serine
      peptidase 1 (HtrA1) gene product whose overexpression in the developing forebrain
      recapitulated some of the aspects of the Dicer(-/-) phenotype. MiR-30e and miR
      181d were identified as posttranscriptional negative regulators of HtrA1 by
      binding to its 3' untranslated region. In vivo overexpression of miR-30e and miR
      181d in Dicer(-/-) forebrain rescued RG proliferation defects.

PMID- 22854830
TI  - Inferior sinus venosus defects: anatomic features and echocardiographic
      correlates.
AB  - Inferior sinus venosus defects (SVDs) are rare imperfections located in the
      inferior portion of the atrial septum, leading to an overriding inferior vena
      cava (IVC) and an interatrial connection. These defects have increased risk of
      anomalous pulmonary venous return (PAPVR) and often are confused with secundum
      atrial septal defects (ASDs) with inferior extension. The authors sought to
      review their experience with inferior SVDs and to establish at their institution
      an echocardiographic definition that differentiates inferior SVDs from secundum
      ASDs with inferior extension. The study identified 161 patients 1.5 to 32 years
      of age who had undergone repair of a secundum ASD with inferior extension or
      inferior SVD over the preceding 10 years. All surgical notes, preoperative
      transthoracic echocardiograms (TTEs), and preoperative transesophageal
      echocardiograms (TEEs) were reviewed. Based on the surgical notes, 147 patients
      were classified as having a secundum ASD (147/161, 91 %) and 14 patients (9 %) as
      having an inferior SVD. The study identified PAPVR in 7 % (1/14) of the patients
      with inferior SVDs and 3.5 % (5/14) of the patients with secundum ASDs. Surgical
      diagnosis and preoperative TTE correlated for 143 (89 %) of the 161 patients.
      Using a strict anatomic and echocardiographic definition with a blinded observer,
      the majority of the defects (14/18, 78 %) were reclassified correctly after
      review of their TTE images, and 100 % of the defects were correctly reclassified
      after TEE image review. Accurate diagnosis of inferior SVDs remains challenging.
      The data from this study demonstrate that use of a strict anatomic and
      echocardiographic definition (a defect that originates in the mouth of the IVC
      and continues into the inferoposterior border of the left atrium, leaving no
      residual atrial septal tissue at the inferior margin) allows for accurate
      differentiation between secundum ASDs with inferior extension and inferior SVDs.
      This differentiation is extremely important in planning for surgical versus
      device closure of these rare defects.

PMID- 22854831
TI  - Intraoperative transesophageal echocardiogram using an intracardiac ultrasound
      catheter in a congenital heart surgery: a case report.
AB  - Transesophageal echocardiography (TEE) during cardiac surgery is a routine
      procedure. The use of pediatric TEE probes is limited in small infants weighing
      less than 5 kg. Recent reports have shown the safety of monoplane intravascular
      ultrasound catheters in transesophageal echocardiograms. This report describes
      the case of a newborn with total anomalous pulmonary venous return who underwent
      cardiac surgery. A pre- and postbypass TEE examination was performed, with
      successful visualization of the cardiac anatomy and function and no
      complications.

PMID- 22854832
TI  - Management strategies after cardiac surgery in an infant with human rhinovirus.
AB  - This report presents management strategies after cardiopulmonary bypass surgery
      for an infant with community-acquired rhinovirus bronchiolitis. The case report
      emphasizes human rhinovirus as a lower respiratory pathogen, the difficulty
      treating the complications of human rhinovirus for an infant with cyanotic
      congenital heart disease after cardiac surgery, and the importance of
      preoperative evaluation for this respiratory infection in high-risk infants
      before cardiac surgery. 

PMID- 22854836
TI  - Nestin expression is increased in the suprabasal epidermal layer in psoriasis
      vulgaris.
AB  - We investigated the expression of both epidermal fatty acid-binding protein
      (FABP5), a marker of transit amplifying cells, and nestin, a putative marker of
      epidermal stem cells, in psoriatic epidermis and in normal human cultured
      keratinocytes. In lesional psoriatic epidermis, immunostaining showed that the
      suprabasal layer was positive for nestin, with some cells co-expressing FABP5.
      Flow cytometric analysis revealed that the expression of both nestin and FABP5
      were increased in keratinocytes cultured in a low concentration of calcium
      relative to those cultured in a high concentration of calcium. These results
      suggest that nestin and FABP5 are expressed in actively proliferating
      keratinocytes in vitro and in the suprabasal layer in lesional psoriatic
      epidermis, and that double-positive cells may identify transit amplifying cells
      in the epidermis.

PMID- 22854837
TI  - Migration: VEGF suppresses invasion.

PMID- 22854841
TI  - Changes in permeability of the plasma membrane of myoblasts to fluorescent dyes
      with different molecular masses under sustained uniaxial stretching.
AB  - Deep tissue injury (DTI) is a serious pressure ulcer which onsets in skeletal
      muscle tissues adjacent to weight-bearing bony prominences. Recent literature
      points at sustained large deformations in muscle tissue, which translate to
      static stretching of the plasma membrane (PM) at the cell-scale, as the primary
      cause of accumulated cell death in DTI. It has been specifically suggested that
      prolonged exposure to large tensional PM strains interferes with normal cellular
      homeostasis, primarily by affecting transport through the PM which could become
      more permeable when stretched. In this context, using confocal imaging and
      fluorescence-activated cell sorter (FACS), we visualized and quantified here the
      uptake of fluorescent Dextran dye by myoblasts that were statically stretched
      uniaxially, up to physiological strains of 3%, 6% and 9%, using two different
      molecular masses for the Dextran (4kDa and 20kDa). The confocal and FACS studies
      provided consistent evidence that the permeability of the PM increased at large
      static deformations. Furthermore, the FACS data indicated that the kinetics of
      the PM permeability very likely depends on the size of the biomolecular marker.
      Both results were consistent with reports published in the neurotrauma literature
      on the kinetics of uptake of fluorescent biomolecules by dynamically stretched
      neurons; hence there are some analogues in the biomechanical pathways of cellular
      level injury between DTI and impact insults. The present work provides additional
      empirical support to the theory of cell-scale deformation-diffusion damage in the
      etiology of DTI, and may lead to better understanding of time courses for onset
      of cellular damage in DTI, by exploring mass transport processes across the PM of
      the involved cells.

PMID- 22854842
TI  - Feasibility of diagnostic criteria for psychosomatic research in India: a pilot
      qualitative evaluation.

PMID- 22854843
TI  - Literature review of outcome parameters used in studies of Geriatric Fracture
      Centers.
AB  - INTRODUCTION: A variety of multidisciplinary treatment models have been described
      to improve outcome after osteoporotic hip fractures. There is a tendency toward
      better outcomes after implementation of the most sophisticated model with a
      shared leadership for orthopedic surgeons and geriatricians; the Geriatric
      Fracture Center. The purpose of this review is to evaluate the use of outcome
      parameters in published literature on the Geriatric Fracture Center evaluation
      studies. MATERIALS AND METHODS: A literature search was performed using Medline
      and the Cochrane Library to identify Geriatric Fracture Center evaluation
      studies. The outcome parameters used in the included studies were evaluated.
      RESULTS: A total of 16 outcome parameters were used in 11 studies to evaluate
      patient outcome in 8 different Geriatric Fracture Centers. Two of these outcome
      parameters are patient-reported outcome measures and 14 outcome parameters were
      objective measures. CONCLUSION: In-hospital mortality, length of stay, time to
      surgery, place of residence and complication rate are the most frequently used
      outcome parameters. The patient-reported outcomes included activities of daily
      living and mobility scores. There is a need for generally agreed upon outcome
      measures to facilitate comparison of different care models.

PMID- 22854844
TI  - Siderophore-based detection of Fe(III) and microbial pathogens.
AB  - Siderophores are low-molecular-weight iron chelators that are produced and
      exported by bacteria, fungi and plants during periods of nutrient deprivation.
      The structures, biosynthetic logic, and coordination chemistry of these molecules
      have fascinated chemists for decades. Studies of such fundamental phenomena guide
      the use of siderophores and siderophore conjugates in a variety of medicinal
      applications that include iron-chelation therapies and drug delivery. Sensing
      applications constitute another important facet of siderophore-based
      technologies. The high affinities of siderophores for both ferric ions and
      siderophore receptors, proteins expressed on the cell surface that are required
      for ferric siderophore import, indicate that these small molecules may be
      employed for the selective capture of metal ions, proteins, and live bacteria.
      This minireview summaries progress in methods that utilize native bacterial and
      fungal siderophore scaffolds for the detection of Fe(III) or microbial pathogens.

PMID- 22854838
TI  - The influence of race and ethnicity on the biology of cancer.
AB  - It is becoming clear that some of the differences in cancer risk, incidence and
      survival among people of different racial and ethnic backgrounds can be
      attributed to biological factors. However, identifying these factors and
      exploiting them to help eliminate cancer disparities has proved challenging. With
      this in mind, we asked four scientists for their opinions on the most crucial
      advances, as well as the challenges and what the future holds for this important
      emerging area of research.

PMID- 22854845
TI  - Photo-controllable electronic switches based on azopyridine derivatives.
AB  - Stable photo-controllable electronic switches based on new light-sensitive
      azopyridines are reported herein. Such systems produce notable variations in the
      cathodic current density on working at low reduction potentials when UV light
      falls on them. The appropriate design of the azopyridine chromophore allows
      modulating the response time of the final opto-electronic switch.

PMID- 22854846
TI  - Encapsulation of divalent tetrahedral oxyanions of sulfur within the rigidified
      dimeric capsular assembly of a tripodal receptor: first crystallographic evidence
      of thiosulfate encapsulation within neutral receptor capsule.
AB  - A simple tris(2-aminoethyl)amine based meta-chloro substituted tripodal thiourea
      receptor L has been extensively studied with two divalent oxyanions of sulfur,
      such as sulfate and thiosulfate, with identical dimensionality. The solid state
      crystal structure of the anion complexes with L reveal that the anions are
      encapsulated within the dimeric rigid capsular assembly of the receptor via N
      H...anion interactions. To the best of our knowledge this is the first report on
      the encapsulation of thiosulfate within dimeric capsular assembly of a neutral
      receptor. The tight capsular sizes for both anion complexes are quite comparable,
      whereas the coordination mode of the anions and the hydrogen bonding parameters
      are significantly varied. The three dimensional solid state structural
      orientations of the capsular complexes are mainly governed by the Cl...Cl (for
      thiosulfate complex) and Cl...S (for sulfate complex) halogen bonding
      interactions. The solution-state binding and encapsulation of oxyanions by N
      H...anion hydrogen bonding has also been confirmed by quantitative (1)H NMR
      titration and 2D NOESY NMR experiments. Both the experiments confirm that in
      contradiction of 2:1 solid state binding, in solution the studied anions are
      bound within the pseudocavity of the receptor with 1:1 binding stoichiometry.
      Moreover, the change in chemical shifts of thiourea -NH protons and the binding
      constant values suggest the receptor-sulfate interaction is more energetically
      favorable compared to the receptor thiosulfate interaction.

PMID- 22854847
TI  - Familiarity with current practices of granting and maintaining privileges in
      pediatric interventional radiology--a worldwide survey of the members of the
      Society for Pediatric Interventional Radiology (SPIR).
AB  - BACKGROUND: Physician credentialing is a complex process driven by the demand for
      quality improvement in health care. In the U.S., the Joint Commission Standard of
      2007 has tied hospital accreditation to credentialing through mandated use of the
      Focused Professional Practice Evaluation (FPPE) and Ongoing Professional Practice
      Evaluation (OPPE). OBJECTIVE: To assess pediatric interventional radiologists'
      knowledge of how institutions grant them privileges. MATERIALS AND METHODS:
      Members of the Society for Pediatric Interventional Radiology (SPIR) were sent a
      web-based survey regarding credentialing. RESULTS: Of 122 members from 19
      countries, 81 (66%) responded, and of these 81, 59 (73%) were familiar with their
      hospital's privileging process. Of 49 U.S. respondents and 32 non-U.S.
      respondents, 37 (76%) and 17 (53%), respectively, stated that interventional
      radiology credentialing was different from diagnostic radiology credentialing. Of
      the 49 U.S. respondents, 24 (49%) reported an OPPE, and of the 32 non-U.S.
      respondents, 8 (25%) reported an ongoing evaluation. The U.S. OPPE is performed
      at shorter intervals than its international equivalent. CONCLUSION: Four years
      after the Joint Commission defined the FPPE and OPPE, separate credentialing of
      pediatric interventional radiology from pediatric diagnostic radiology is more
      likely in the U.S. than internationally, and U.S. pediatric interventional
      radiologists are more likely to have a defined ongoing professional evaluation
      and to be evaluated every 6 months or more frequently. There are many SPIR
      members who do not know how they obtain privileges and/or are not knowingly
      subject to an OPPE. This lack of knowledge may affect future education of
      interventional radiologists as well as the definition of pediatric interventional
      radiology practices within individual institutions.

PMID- 22854858
TI  - The health promoting hospital movement in Taiwan: recent development and gaps in
      workplace.
AB  - OBJECTIVE: To examine the development in healthcare workplace health promotion
      (WHP) in Taiwan through the Health Promoting Hospital (HPH) initiative. METHODS:
      A cross-sectional survey was conducted with a self-administered questionnaire,
      involving all 55 hospitals committed to the HPH approach (HP hospitals) as of the
      end of 2009; 52 completed the questionnaire. RESULTS: Fifty of 52 hospitals
      perceived a change in organizational capacity which mainly occurred in the areas
      of re-aligning strategies (96 %) and more resources (71 %). Regarding re-aligning
      strategies, 85 % of the hospitals engaged in increased staff participation, 66 %
      in staff-oriented health services. CONCLUSIONS: The HPH initiative has led to new
      developments in capacity building of WHP among HP hospitals in Taiwan, and this
      study has mapped a pattern of such developments.

PMID- 22854860
TI  - The many ways to be marginal in a group.
AB  - Previous theory and research primarily address marginal group members on the path
      to achieve core membership status. The authors argue that these only represent
      one form of marginality and that there are many other ways to be marginal within
      the group. The authors develop a dynamic model in which marginality is
      conceptualized as resulting from group and individual negotiation about inclusion
      (the Marginality as Resulting From Group and Individual Negotiation About
      Inclusion [MARGINI] model), and where individual and group inclusion goals can
      converge (resulting in relatively stable forms of marginality) or diverge
      (resulting in less stable forms of marginality). When the marginal position is
      unstable, individuals can either be motivated to move toward or move further away
      from the group, and such changing inclusion goals are associated with different
      emotions and behaviors. The authors argue that one needs to understand the
      interplay between individual and group inclusion goals to predict and explain the
      full complexity and diversity of the behavior of marginal group members.

PMID- 22854859
TI  - Specific capture and temperature-mediated release of cells in an aptamer-based
      microfluidic device.
AB  - Isolation of cells from heterogeneous mixtures is critically important in both
      basic cell biology studies and clinical diagnostics. Cell isolation can be
      realized based on physical properties such as size, density and electrical
      properties. Alternatively, affinity binding of target cells by surface
      immobilized ligands, such as antibodies, can be used to achieve specific cell
      isolation. Microfluidics technology has recently been used in conjunction with
      antibody-based affinity isolation methods to capture, purify and isolate cells
      with higher yield rates, better efficiencies and lower costs. However, a method
      that allows easy release and collection of live cells from affinity surfaces for
      subsequent analysis and detection has yet to be developed. This paper presents a
      microfluidic device that not only achieves specific affinity capture and
      enrichment, but also enables non-destructive, temperature-mediated release and
      retrieval of cells. Specific cell capture is achieved using surface-immobilized
      aptamers in a microchamber. Release of the captured cells is realized by a
      moderate temperature change, effected via integrated heaters and a temperature
      sensor, to reversibly disrupt the cell-aptamer interaction. Experimental results
      with CCRF-CEM cells have demonstrated that the device is capable of specific
      capture and temperature-mediated release of cells, that the released cells remain
      viable and that the aptamer-functionalized surface is regenerable.

PMID- 22854861
TI  - What we should expect from theories in social psychology: truth, abstraction,
      progress, and applicability as standards (TAPAS).
AB  - The construction and development of theory is one of the central routes to
      scientific progress. But what exactly constitutes a good theory? What is it that
      people might expect from an ideal theory? This article advances a new model,
      which delineates truth, abstraction, progress, and applicability as standards
      (TAPAS) for a good theory. After providing the rationale for TAPAS, this article
      evaluates several social-psychological theories in terms of TAPAS, especially
      classic theories, and illustrates its utility with some more recent theoretical
      contributions of social psychology. This article concludes by outlining
      recommendations for effective theory construction and development, such as the
      utility of meta-analytic approaches for pursuing truth, the utility of theory
      oriented courses and journals for pursuing abstraction, and the utility of
      adversarial collaboration for pursuing progress, and reaching out to major
      personal or societal issues for pursuing applicability.

PMID- 22854862
TI  - Features of multifinality.
AB  - Diverse facets of the multifinality configuration in goal-directed behavior are
      identified and empirically explored. The multifinality construct denotes a
      motivational structure wherein a single means is linked to several ends. A
      multifinality configuration maximizes value that a given means promises to
      deliver while sacrificing expectancy of attainment due to a dilution effect.
      Several phenomena implied by multifinality theory are investigated, including an
      unconscious quest for multifinal means, the constraints that such quest imposes
      on means to a focal goal, and structural conditions under which an activity may
      be experienced as intrinsically motivated. Multifinality phenomena appear in
      numerous domains of social cognition, and the present theory offers a novel
      perspective on classic motivational effects.

PMID- 22854863
TI  - Effect of humic acid on nickel(II) sorption to Ca-montmorillonite by batch and
      EXAFS techniques study.
AB  - The influence of humic acid (HA) on Ni(II) sorption to Ca-montmorillonite was
      examined by using a combination of batch sorption experiments and extended X-ray
      absorption fine structure (EXAFS) spectroscopy technique. The sorption of Ni(II)
      on HA-montmorillonite hybrids is strongly dependent on pH and temperature. At low
      pH, the sorption of Ni(II) is mainly dominated by Ni-HA-montmorillonite and outer
      sphere surface complexation. The EXAFS results indicate that the first
      coordination shell of Ni(II) consists of ~6 O atoms at the interatomic distances
      of ~2.04 A in an octahedral structure. At high pH, binary Ni-montmorillonite
      surface complexation is the dominant sorption mechanism. EXAFS analysis indicates
      the formation of mononuclear complexes located at the edges of Ca-montmorillonite
      platelets at pH 7.5, while a Ni-Al layered double hydroxide (LDH) phase at the Ca
      montmorillonite surface formed with pH 8.5. At pH 10.0, the dissolved HA-Ni(II)
      complexation inhibits the precipitation of Ni hydroxide, and Ni-Al LDH phase
      forms. The rise of temperature increases the sorption capacity of Ni(II), and
      promotes Ni-Al LDH phase formation and the growth of crystallites. The results
      are important to evaluate the physicochemical behavior of Ni(II) in the natural
      environment.

PMID- 22854864
TI  - Dehydration from conserved stem regions is fundamental for ligand-dependent
      conformational transition of the adenine-specific riboswitch.
AB  - Conformational dynamics and observed equilibrium constants for ligand binding of
      the adenine-specific riboswitch (add-A riboswitch) in the absence of Mg(2+) and
      presence of various concentrations of poly-ethylene glycol having an average
      molecular weight of 200 indicated that 54.2 water molecules were released from P2
      and P3 stem regions of the add-A riboswitch during conformational transition upon
      the binding of 2-aminopurine, an analog of the natural ligand adenine.

PMID- 22854869
TI  - Long-term follow-up results of the Cloward procedure for cervical spondylotic
      myelopathy.
AB  - PURPOSE: To assess the long-term results of anterior cervical discectomy and
      fusion using the Cloward procedure for the treatment of cervical spondylotic
      myelopathy, and to identify possible clinical outcome predictors. METHODS: A
      total of 14 cases with a 10-year postoperative follow-up were available (82.4 %
      of the surviving patients). Patients underwent preoperative and postoperative
      neurological examination. The symptom severity was graded according to the Nurick
      scale. MRI measurements were obtained preoperatively. Cervical spine radiographs
      were obtained preoperatively and at the time of follow-up. RESULTS: The mean
      improvement of the clinical status of patients on the Nurick scale was 1.43 +/-
      0.51 (range 1-2) with respect to the baseline values (p < 0.001), with a 62.5 %
      recovery rate. A positive association between the improvement of the Nurick scale
      and the length of follow-up was detected with an age-adjusted univariate analysis
      (p = 0.042). The Nurick grade improvement was also directly related to
      preoperative lower limb hyperreflexia (p = 0.039), spasticity (p = 0.017), and
      bladder dysfunction (p = 0.048). At the time of follow-up, an adjacent discopathy
      was noted above and below the operated level(s) in eight and six patients,
      respectively. CONCLUSIONS: The Cloward technique is a safe and effective
      procedure for the treatment of cervical spondylotic myelopathy. The patients'
      preoperative neurological status and the length of follow-up affect the grade of
      postoperative ambulatory improvement.

PMID- 22854870
TI  - X-ray lithography and small-angle X-ray scattering: a combination of techniques
      merging biology and materials science.
AB  - The advent of micro/nanotechnology has blurred the border between biology and
      materials science. Miniaturization of chemical and biological assays, performed
      by use of micro/nanofluidics, requires both careful selection of the methods of
      fabrication and the development of materials designed for specific applications.
      This, in turn, increases the need for interdisciplinary combination of suitable
      microfabrication and characterisation techniques. In this review, the advantages
      of combining X-ray lithography, as fabrication technique, with small-angle X-ray
      scattering measurements will be discussed. X-ray lithography enables the
      limitations of small-angle X-ray scattering, specifically time resolution and
      sample environment, to be overcome. Small-angle X-ray scattering, on the other
      hand, enables investigation and, consequently, adjustment of the nanostructural
      morphology of microstructures and materials fabricated by X-ray lithography.
      Moreover, the effect of X-ray irradiation on novel materials can be determined by
      use of small-angle X-ray scattering. The combination of top-down and bottom-up
      methods to develop new functional materials and structures with potential in
      biology will be reported.

PMID- 22854871
TI  - The use of PEEK nanorod arrays for the fabrication of nanoporous surfaces under
      high temperature: SiNx example.
AB  - Large area silicon nitride (SiN(x)) nanoporous surfaces are fabricated using
      poly(ether-ether-ketone) (PEEK) nanorod arrays as a template. The procedure
      involves manipulation of nanoporous anodic aluminum oxide (AAO) templates in
      order to form an ordered array of PEEK nanopillars with high temperature
      resistant characteristics. In this context, self-ordered AAO templates are
      infiltrated with PEEK melts via the "precursor film" method. Once the melts have
      been crystallized in the porous structure of AAO, the basis alumina layer is
      removed, yielding an ordered array of PEEK nanopillars. The resulting structure
      is a high temperature and chemical resistant polymeric nanomold, which can be
      utilized in the synthesis of nanoporous materials under aggressive conditions.
      Such conditions are high temperatures (up to 320  degrees C), vacuum, or extreme
      pH. For example, SiN(x) nanopore arrays have been grown by plasma enhanced
      chemical vapor deposition at 300  degrees C, which can be of interest as mold for
      nanoimprint lithography, due to its hardness and low surface energy. The SiN(x)
      nanopore array portrays the same characteristics as the original AAO template:
      120 nm diameter pores and an interpore distance of 430 nm. Furthermore, the
      aspect ratio of the SiN(x) nanopores can be tuned by selecting an AAO template
      with appropriate conditions. The use of PEEK as a nanotemplate extends the
      applicability of polymeric nanopatterns into a temperature regime up to now not
      accessible and opens up the simple fabrication of novel nanoporous inorganic
      surfaces.

PMID- 22854872
TI  - Music interventions and physical activity in older adults: a systematic
      literature review and meta-analysis.
AB  - OBJECTIVE: To determine the effectiveness of music interventions in increasing
      physical activity in older adults. METHODS: Searches until March 2011 were
      conducted through CINAHL, MEDLINE, EMBASE, PubMED, AMED, PsychINFO, AUSPORT,
      PEDro, OTseeker, Expanded Academic ASAP, SPORTDiscus, and The Cochrane Library.
      Selection criteria included older adults, music interventions, physical activity
      outcomes, and quantitative designs. Two reviewers independently screened records.
      Study details included objectives, designs, participants, music interventions,
      physical activity outcomes, and results. Risk of bias was assessed using the
      PEDro scale. RESULTS: The review included 12 low to moderate quality studies with
      309 participants. Three meta-analyses conducted for the review (4 trials and 99
      participants) did not demonstrate any within-session differences in comparisons
      between music and no-music interventions. Two individual trials of moderate
      quality demonstrated increased capacity to perform physical activity following
      exercise programs with music over 4 and 8 weeks compared with no-music. There was
      no evidence that any particular music intervention was superior to another.
      CONCLUSION: Evidence from a small number of low to moderate quality trials did
      not demonstrate within-session improvements for older adults who listen to music
      during exercise. However, there may be cumulative benefits following programs
      with music over several weeks.

PMID- 22854873
TI  - [Transcranial brain stimulation after stroke].
AB  - Stroke is the leading cause of disability in adults. In Germany an estimated 1.5
      million stroke survivors have to cope with persisting sensorimotor or cognitive
      deficits and effective therapies are scarce. The idea of using non-invasive brain
      stimulation to treat neuropsychiatric diseases was already born more than 2,000
      years ago (Scribonius largus, 43-48 AD). However, only the development of modern
      non-invasive brain stimulation methods, such as transcranial magnetic stimulation
      (TMS) and transcranial direct current stimulation (tDCS) has made it possible to
      evaluate these ideas. The therapeutic value of these non-invasive brain
      stimulation methods is currently under study for several neuropsychiatric
      diseases, mostly in a proof-of-principle fashion. In this article the focus will
      be on non-invasive brain stimulation to enhance functional regeneration after
      stroke.

PMID- 22854874
TI  - [Therapeutic hypothermia in acute brain injury].
AB  - Induced therapeutic hypothermia (TH) is defined as a controlled reduction of the
      core body temperature below the physiological range. While TH is neuroprotective
      in many different models of brain injury, it is only recommended for patients
      after cardiopulmonary resuscitation and newborns suffering from perinatal hypoxic
      ischemic encephalopathy (HIE). Although a strong association exists between
      elevated body core temperature (fever) and worsening of outcome, TH has so far
      not been proven to influence outcome after ischemic stroke, intracerebral
      hemorrhage or subarachnoidal hemorrhage because of insufficient clinical data.
      This review summarizes the data on TH for different clinical indications and
      discusses relevant aspects of its use in neurological intensive care units.

PMID- 22854875
TI  - Usefulness of fetal monitoring in intrahepatic cholestasis of pregnancy: a
      prospective study.
AB  - AIM: To study the role of fetal surveillance in intrahepatic cholestasis of
      pregnancy. MATERIALS AND METHODS: A total of 69 women with obstetric cholestasis
      were included. Fetal surveillance began at 34 weeks or later at diagnosis and
      included daily maternal record of fetal movements, biophysical profile (i.e., non
      stress test, amniotic fluid volume assessment using the four quadrant amniotic
      fluid index), and Doppler flow velocimetry. Fetal monitoring was done weekly
      before 36 weeks and biweekly after that. RESULTS: There were no abnormal non
      stress test readings and all pregnancies had good biophysical profile. One
      hundred and sixty Doppler measurements [Systolic-Diastolic (S/D ratio) and
      Pourcelot index (PR)] were taken from 67 patients at scheduled intervals during
      the study period. Findings were compared to gestation matched reference values of
      Doppler flow velocities of umbilical artery of normal pregnant population. Fifty
      six out of 160 PR indices and 33 out of 162 S/D ratio readings were above 2 SD
      and these results were found to be statistically significant. However, there was
      no significant correlation with the serum levels of alanine transaminase (r=
      0.071) or with aspartate transaminase (r=0.058). Further, there was no
      correlation of Doppler with rates of preterm delivery or meconium-stained liquor.
      CONCLUSION: Doppler investigation of the umbilical artery might be of some value
      in recognition of the specific risk of fetal compromise in pregnancies
      complicated by intrahepatic cholestasis.

PMID- 22854876
TI  - Vaginal sacrocolporectopexy for the surgical treatment of uterine and vaginal
      vault prolapses: confirmation of the surgical method and perioperative results of
      101 cases.
AB  - PURPOSE: In this study, we sought to confirm the surgical method of vaginal
      sacrocolporectopexy and previously reported positive perioperative results of
      this procedure in a large patient group. We describe the approach which offers a
      vaginal, safe alternative to sacrospinous repair, laparoscopic or open
      vaginosacropexy and the use of synthetic meshes to treat pelvic organ prolapse.
      METHODS: We conducted a monocentric, prospective, nonrandomized study for
      treatment of patients with uterine and vaginal vault relapse (grade 2-4). All
      patients underwent a preoperative urogynecological urodynamic examination. We
      focus on method, operative time, complications, blood transfusions, hospital stay
      and clinical data. RESULTS: Between March 2006 and March 2011, 101 consecutive
      patients of mean age 64 (40-89) years, with sub or total uterine prolapse (n=69,
      grade 2-4) and vaginal vault prolapse (n=32, grade 2-4) were treated with vaginal
      sacrocolporectopexy. Cystocele (grade 2-4) was found in 88 (87.1%) and rectocele
      (grade 2-4) in 43 (42.5%) patients. Mean duration of surgery with
      sacrocolporectopexy was 70 min (28-165) without hysterectomy, and 76 min (40-219)
      with hysterectomy. Regression analysis of all patients (n=101) showed a
      significant decrease of operative time in the group without hysterectomy after 40
      cases. Three bladder lesions, two in patients with a history of hysterectomy,
      occurred during surgery and were corrected intraoperatively without further
      complications. No patient required a blood transfusion. Hemoglobin levels
      decreased slightly from a preoperative mean of 13.6 mg/dl (10.3-15.7) to a
      postoperative mean of 11.7 mg/dl (8.6-14.7). CONCLUSION: Vaginal
      sacrocolporectopexy is a safe vaginal method for the treatment of sub-/total
      uterine/vaginal vault prolapse.

PMID- 22854879
TI  - Comparing single-frequency bioelectrical impedance analysis against deuterium
      dilution to assess total body water.
AB  - BACKGROUND/OBJECTIVES: In this study, we aimed to validate the accuracy of single
      frequency bioelectrical impedance analysis (SF-BIA) at 50 kHz to assess total
      body water (TBW) against the reference technique deuterium dilution (D(2)O) and
      to explore if the simple clinical parameters extracellular fluid (ECF)
      composition and body shape explain individual differences between D(2)O and SF
      BIA (Diff(BIA-D(2)O)). SUBJECTS/METHODS: We assessed TBW with D(2)O and SF-BIA in
      26 women and 26 men without known disease or anomalous body shapes. In addition,
      we measured body shape with anthropometry and ECF composition (osmolality,
      albumin, glucose, urea, creatinine, sodium and potassium). RESULTS: On group
      average, SF-BIA to predict TBW agreed well with D(2)O (SF-BIA, 39.8 +/- 10.1 l;
      D(2)O, 40.4 +/- 10.2 l; and Diff(BIA-D(2)O) -0.7 l). In four individuals
      ('outliers'; 15% of the study population), Diff(BIA-D(2)O) was high (-6.8 to +3.8
      l). Diff(BIA-D(2)O) was associated with individual variations in body shape
      rather than ECF composition. Using gender-specific analysis, we found that
      individual variability of waist circumference in men and arm length in women
      significantly contributed to Diff(BIA-D(2)O). When removing the four 'outliers',
      these associations were lost. CONCLUSIONS: In the majority of our sample, BIA
      agreed well with D(2)O. Adjusting for individual variability in body shape by
      anthropometrical assessment could possibly improve the accuracy of SF-BIA for
      individuals who deviate from mean values with respect to body shape. However,
      further studies with higher subject numbers are needed to confirm our findings.

PMID- 22854878
TI  - Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study
      and meta-analysis.
AB  - Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D),
      but the epidemiological evidence is inconclusive. The aim of this study is to
      examine the prospective association of FVI with T2D and conduct an updated meta
      analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC
      InterAct) prospective case-cohort study nested within eight European countries, a
      representative sample of 16,154 participants and 12,403 incident cases of T2D
      were identified from 340,234 individuals with 3.99 million person-years of follow
      up. For the meta-analysis we identified prospective studies on FVI and T2D risk
      by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct,
      estimated FVI by dietary questionnaires varied more than twofold between
      countries. In adjusted analyses the hazard ratio (95% confidence interval)
      comparing the highest with lowest quartile of reported intake was 0.90 (0.80
      1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables.
      Among FV subtypes, only root vegetables were inversely associated with diabetes
      0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including
      EPIC-InterAct, comparing the highest with lowest category for FVI was associated
      with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables
      separately were not associated with diabetes. Among FV subtypes, only green leafy
      vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated
      with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be
      beneficial for the prevention of diabetes, while total FVI may exert a weaker
      overall effect.

PMID- 22854880
TI  - Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative
      stress, inflammation and hemostasis in obese adults at risk for insulin
      resistance.
AB  - BACKGROUND/OBJECTIVES: Flavanols may provide protection against insulin
      resistance, but little is known about the amounts and types of flavanols that may
      be efficacious. SUBJECTS/METHODS: This study was designed to determine whether
      cocoa flavanols, over a range of intakes, improve biomarkers of glucose
      regulation, inflammation and hemostasis in obese adults at risk for insulin
      resistance. As an adjunct, green tea and cocoa flavanols were compared for their
      ability to modulate these biomarkers. In a randomized crossover design, 20 adults
      consumed a controlled diet for 5 days along with four cocoa beverages containing
      30-900 mg flavanol per day, or tea matched to a cocoa beverage for monomeric
      flavanol content. RESULTS: Cocoa beverages produced no significant changes in
      glucose, insulin, total area under the concentration-time curve (AUC) for glucose
      or total insulin AUC. As the dose of cocoa flavanols increased, total 8
      isoprostane concentrations were lowered (linear contrast, P=0.02), as were C
      reactive protein (CRP) concentrations (linear contrast, P=0.01). The relationship
      between cocoa flavanol levels and interleukin-6 (IL-6) concentrations was
      quadratic, suggesting that a maximum effective dose was achieved (quadratic
      contrast, P=0.01). There were no significant effects on measured indices of
      glucose regulation, nor on those of total 8-isoprostane, CRP and IL-6
      concentrations, when cocoa and green tea were compared. However, relative to
      cocoa, green tea lowered fibrinogen concentrations (P=0.0003). CONCLUSIONS: Short
      term intake of cocoa and green tea flavanols does not appear to improve glucose
      metabolism; they do affect selected markers of one or more measures of oxidative
      stress, inflammation or hemostasis in obese adults at risk for insulin
      resistance.

PMID- 22854881
TI  - Kinetics of alpha hydrogen abstractions from thiols, sulfides and thiocarbonyl
      compounds.
AB  - Hydrogen abstraction reactions involving organosulfur compounds play an important
      role in many industrial, biological and atmospheric processes. Despite their
      chemical relevance, little is known about their kinetics. In this work a group
      additivity model is developed that allows predicting the Arrhenius parameters for
      abstraction reactions of alpha hydrogen atoms from thiols, alkyl sulfides, alkyl
      disulfides and thiocarbonyl compounds by carbon-centered radicals at temperatures
      ranging from 300 to 1500 K. Rate coefficients for 102 hydrogen abstractions were
      obtained using conventional transition state theory within the high-pressure
      limit. Electronic barriers were calculated using the CBS-QB3 method and the rate
      coefficients were corrected for tunneling and hindered rotation about the
      transitional bond. Group additivity values for 46 groups are determined. To
      account for resonance and hyperconjugative stabilization in the transition state,
      8 resonance corrections were fitted to a set of 32 reactions. The developed group
      additivity scheme was validated using a test set containing an additional 30
      reactions. The group additivity scheme succeeds in reproducing the rate
      coefficients on average within a factor of 2.4 at 300 K and 1.4 at 1000 K. Mean
      absolute deviations of the Arrhenius parameters amount to, respectively, 2.5 kJ
      mol(-1) for E(a) and 0.13 for log A, both at 300 and 1000 K. This work hence
      illustrates that the recently developed group additivity methods for Arrhenius
      parameters extrapolate successfully to hetero-element containing compounds.

PMID- 22854882
TI  - Aortic fistula after neoadjuvant chemoradiotherapy and esophagectomy for
      esophageal carcinoma: an unusual cause of sudden death.
AB  - Aortic fistula to the enteric tract is an uncommon but recognized complication of
      esophagectomy, whereas an aortorespiratory fistula is usually described in the
      setting of aortic disease or previous aortic surgery. We describe 2 cases of
      fatal aortic fistula occurring after esophagectomy and neoadjuvant
      chemoradiotherapy, both encountered at autopsy.The first case is an
      aortobronchial fistula occurring in a 47-year-old male in the early postoperative
      setting. Death was caused by rupture of the fistula into the posterior
      mediastinum with transhiatal extension and hemoperitoneum. The tissue adjacent to
      the fistula showed radiation effect, and an esophageal stent had been placed
      before surgery. The second case is an aortogastric tube fistula occurring in a 50
      year-old male 2 years after surgery and resulting in fatal gastrointestinal
      hemorrhage. The fistula involved the site of anastomosis and a surgical clip was
      present in the adjacent soft tissue.The development of aortic fistula after
      esophagectomy for esophageal carcinoma is rare, but should be considered at
      autopsy as a potential cause of unexpected, sudden death in these patients.
      Possible inciting mechanisms in this setting include the presence of foreign
      material (stent placement and surgical clips) and previous chemoradiation.

PMID- 22854883
TI  - Ethnic differences in the prognostic utility of rheumatoid factor isotypes and
      anticyclic citrullinated peptides in rheumatoid arthritis patients: a cross
      sectional study.
AB  - OBJECTIVES: The prognostic significance of rheumatoid factor (RF) and anticyclic
      citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains
      contentious due to the conflicting lines of evidence. This study aims to
      determine the association between RF isotypes and anti-CCP with disease severity
      in RA patients from three ethnic groups. METHODS: A total of 147 RA patients from
      three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the
      1987 American College of Rheumatology (ACR) revised criteria for RA were
      recruited into this study. The seroprevalence of RF isotypes immunoglobulin
      (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme
      linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was
      performed to assess the independent effects of autoantibody status on the
      development of deforming and erosive RA and the presence of extra-articular
      manifestations (EAM). RESULTS: In Chinese patients, we found a significant
      association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive
      disease, as well as IgM RF and IgG RF with the presence of joint deformities. In
      Indian patients, IgM RF was associated with deforming disease, whereas none of
      the antibodies were associated with disease severity in Malay patients.
      Multinomial regression analysis revealed that IgG RF was the most important
      predictor variable for erosive disease in Chinese patients, and IgM RF the only
      predictor variable associated with deforming disease in both Chinese and Indian
      RA patients. CONCLUSIONS: There is variability in the phenotypic association of
      RF isotypes and anti-CCP in relation to disease severity of RA in the three
      ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of
      severe disease in Chinese and Indian patients.

PMID- 22854884
TI  - Conversion of D-penicillaminato trinuclear to mononuclear palladium(II) structure
      by diamine ligands: remarkable enantioselectivity toward racemic 1,2
      cyclohexanediamine.
AB  - The reactions of an S-bridged trinuclear palladium(II) complex, [Pd(3)(D-pen
      N,O,S)(3)] (D-H(2)pen = D-penicillamine), with ethylenediamine (en) and racemic
      (R,R/S,S) 1,2-cyclohexanediamine (chxn) in water gave mononuclear palladium(II)
      complexes, [Pd(D-pen-N,S)(en)] (1) and [Pd(D-pen-N,S)(chxn)] (2), respectively.
      Of two diastereomers, [Pd(D-pen-N,S)(R,R-chxn)] (2(R)) and [Pd(D-pen-N,S)(S,S
      chxn)] (2(S)), possible for 2, 2(S) was exclusively isolated in a high yield.

PMID- 22854885
TI  - I2 promoted domino oxidative cyclization for one-pot synthesis of 2
      acylbenzothiazoles via metal-free sp3 C-H functionalization.
AB  - An I(2) promoted domino protocol was developed to construct 2-acylbenzothiazoles
      from simple and readily available aromatic ketones/unsaturated methyl ketones and
      o-aminobenzenethiols. The reaction proceeded smoothly under metal-free and
      peroxide-free conditions.

PMID- 22854886
TI  - Pain acceptance-based coping in complex regional pain syndrome Type I: daily
      relations with pain intensity, activity, and mood.
AB  - This study aimed to examine the temporal patterning of pain acceptance-based
      coping, activity, and mood in patients with complex regional pain syndrome Type I
      (CRPS-I), by using a daily diary method. A total of 30 patients with CRPS-I
      seeking treatment in a tertiary pain management center located in Seoul, Korea
      participated in the study. Multilevel random effects analyses indicated that (a)
      engagement in pain acceptance-based coping was significantly associated with
      lower same-day pain and negative mood and greater same-day activity and positive
      mood; (b) pain acceptance-based coping predicted increases in activity on the
      following day; (c) greater pain intensity was significantly associated with lower
      same-day pain acceptance-based coping and activity and greater same-day negative
      mood; and (d) pain intensity did not predict pain acceptance-based coping,
      activity, or mood on the following day. These findings suggest that patients with
      CRPS-I may benefit from responding to pain with acceptance. Further study and
      eventual application of this process in CRPS-I may improve upon the success of
      current approaches to this problem. 

PMID- 22854887
TI  - Subjective cognitive-affective status following thalamic stroke.
AB  - Previous patient studies suggest that thalamic stroke may yield persistent
      deficits in several cognitive domains. At present, the subjective dimension and
      everyday relevance of these impairments is unclear, since many patients with
      thalamic stroke only show minor changes on physical examination. Here, we have
      studied subjective consequences of focal thalamic lesions. A sample of 68
      patients with a history of ischemic thalamic stroke was examined by using
      established clinical self-report questionnaires assessing memory, attention,
      executive functions, emotional status and health-related quality of life. In
      order to control for general factors related to cerebrovascular disease, self
      reports were compared to an age-matched group of 34 patients with a history of
      transient ischemic attack. Thalamic lesions were co-registered to an atlas of the
      human thalamus. Lesion overlap and subtraction analyses were used for lesion-to
      symptom mapping. When both patient groups were compared, no significant
      differences were found for either questionnaire. However, when subgroups were
      compared, patients with infarctions involving the posterior thalamus showed
      significant emotional disturbances and elevated anxiety levels compared to
      patients with more anterior lesions. Our findings thus point to the existence of
      a persistent affective impairment associated with chronic lesions of the
      posterior thalamus. This syndrome may result from damage to connections between
      medial pulvinar and extra-thalamic regions involved in affective processing. Our
      findings suggest that the posterior thalamus may contribute significantly to the
      regulation of mood.

PMID- 22854889
TI  - Regulation of plasma ceramide levels with fatty acid oversupply: evidence that
      the liver detects and secretes de novo synthesised ceramide.
AB  - AIMS/HYPOTHESIS: Plasma ceramide concentrations correlate with insulin
      sensitivity, inflammation and atherosclerotic risk. We hypothesised that plasma
      ceramide concentrations are increased in the presence of elevated fatty acid
      levels and are regulated by increased liver serine C-palmitoyltransferase (SPT)
      activity. METHODS: Lean humans and rats underwent an acute lipid infusion and
      plasma ceramide levels were determined. One group of lipid-infused rats was
      administered myriocin to inhibit SPT activity. Liver SPT activity was determined
      in lipid-infused rats, and obese, insulin resistant mice. The time and palmitate
      dose-dependent synthesis of intracellular and secreted ceramide was determined in
      HepG2 liver cells. RESULTS: Plasma ceramide levels were increased during lipid
      infusion in humans and rats, and in obese, insulin-resistant mice. The increase
      in plasma ceramide was not associated with changes in liver SPT activity, and
      inhibiting SPT activity by ~50% did not alter plasma ceramide levels in lipid
      infused rats. In HepG2 liver cells, palmitate incorporation into extracellular
      ceramide was both dose- and time-dependent, suggesting the liver cells rapidly
      secreted the newly synthesised ceramide. CONCLUSIONS/INTERPRETATION: Elevated
      systemic fatty acid availability increased plasma ceramide but this was not
      associated with changes in hepatic SPT activity, suggesting that liver ceramide
      synthesis is driven by substrate availability rather than increased SPT activity.
      This report also provides evidence that the liver is sensitive to the
      intracellular ceramide concentration, and an increase in liver ceramide secretion
      may help protect the liver from the deleterious effects of intracellular ceramide
      accumulation.

PMID- 22854890
TI  - Urinary podocalyxin is an early marker for podocyte injury in patients with
      diabetes: establishment of a highly sensitive ELISA to detect urinary
      podocalyxin.
AB  - AIMS/OBJECTIVE: Nephropathy, a major complication of diabetes, is the leading
      cause of end-stage renal disease. Recent studies have demonstrated that podocyte
      injury is involved in the onset of and progression to renal insufficiency. Here,
      we describe a novel, highly sensitive ELISA for detecting urinary podocalyxin, a
      glycoconjugate on the podocyte apical surface that indicates podocyte injury,
      particularly in the early phase of diabetic nephropathy. METHODS: Urine samples
      from patients with glomerular diseases (n = 142) and type 2 diabetes (n = 71)
      were used to quantify urinary podocalyxin by ELISA. Urine samples were obtained
      from 69 healthy controls for whom laboratory data were within normal values.
      Podocalyxin was detected in urine by immunofluorescence, immunoelectron
      microscopy and western blotting. RESULTS: Morphologically, urinary podocalyxin
      was present as a vesicular structure; western blotting showed it as a positive
      band at 165-170 kDa. Levels of urinary podocalyxin were elevated in patients with
      various glomerular diseases and patients with diabetes. In patients with
      diabetes, urinary podocalyxin was higher than the cut-off value in 53.8% patients
      at the normoalbuminuric stage, 64.7% at the microalbuminuric stage and 66.7% at
      the macroalbuminuric stage. Positive correlations were observed between urinary
      podocalyxin levels and HbA(1c), urinary beta(2) microglobulin, alpha(1)
      microglobulin and urinary N-acetyl-beta-D-glucosaminidase, although urinary
      podocalyxin levels were not correlated with other laboratory markers such as
      blood pressure, lipid level, serum creatinine, estimated GFR or proteinuria.
      CONCLUSIONS/INTERPRETATION: Urinary podocalyxin may be a useful biomarker for
      detecting early podocyte injury in patients with diabetes.

PMID- 22854891
TI  - ADA/EASD position statement of the treatment of type 2 diabetes: Reply to Rodbard
      HW and Jellinger PS [letter], Scheen AJ [letter] and Ceriello A, Gallo M, Gentile
      S et al [letter].

PMID- 22854892
TI  - Anaerobic bacteria as producers of antibiotics.
AB  - Anaerobic bacteria are the oldest terrestrial creatures. They occur ubiquitously
      in soil and in the intestine of higher organisms and play a major role in human
      health, ecology, and industry. However, until lately no antibiotic or any other
      secondary metabolite has been known from anaerobes. Mining the genome sequences
      of Clostridium spp. has revealed a high prevalence of putative biosynthesis genes
      (PKS and NRPS), and only recently the first antibiotic from the anaerobic world,
      closthioamide, has been isolated from the cellulose degrading bacterium
      Clostridium cellulolyticum. The successful genetic induction of antibiotic
      biosynthesis in an anaerobe encourages further investigations of obligate
      anaerobes to tap their hidden biosynthetic potential.

PMID- 22854893
TI  - Biotransformation of benzene and toluene to catechols by phenol hydroxylase from
      Arthrobacter sp. W1.
AB  - Phenol hydroxylase gene engineered microorganism (PHIND) was used to synthesize
      catechols from benzene and toluene by successive hydroxylation reaction. HPLC-MS
      and (1)H NMR analysis proved that the products of biotransformation were the
      corresponding catechols via the intermediate production of phenols. It was
      indicated that the main products of toluene oxidation were o-cresol and p-cresol.
      3-Methylcatechol was the predominant product for m-cresol biotransformation.
      Formation rate of catechol (25 MUM/min/g cell dry weight) was 1.43-fold higher
      than that of methylcatechols. It was suggested that phenol hydroxylase could be
      successfully used to transform both benzene and toluene to catechols by
      successive hydroxylation.

PMID- 22854894
TI  - Glucosamine as carbon source for amino acid-producing Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum grows with a variety of carbohydrates and carbohydrate
      derivatives as sole carbon sources; however, growth with glucosamine has not yet
      been reported. We isolated a spontaneous mutant (M4) which is able to grow as
      fast with glucosamine as with glucose as sole carbon source. Glucosamine also
      served as a combined source of carbon, energy and nitrogen for the mutant strain.
      Characterisation of the M4 mutant revealed a significantly increased expression
      of the nagB gene encoding the glucosamine-6P deaminase NagB involved in
      degradation of glucosamine, as a consequence of a single mutation in the promoter
      region of the nagAB-scrB operon. Ectopic nagB overexpression verified that the
      activity of the NagB enzyme is in fact the growth limiting factor under these
      conditions. In addition, glucosamine uptake was studied, which proved to be
      unchanged in the wild-type and M4 mutant strains. Using specific deletion
      strains, we identified the PTS(Glc) transport system to be responsible for
      glucosamine uptake in C. glutamicum. The affinity of this uptake system for
      glucosamine was about 40-fold lower than that for its major substrate glucose.
      Because of this difference in affinity, glucosamine is efficiently taken up only
      if external glucose is absent or present at low concentrations. C. glutamicum was
      also examined for its suitability to use glucosamine as substrate for
      biotechnological purposes. Upon overexpression of the nagB gene in suitable C.
      glutamicum producer strains, efficient production of both the amino acid L-lysine
      and the diamine putrescine from glucosamine was demonstrated.

PMID- 22854895
TI  - Response of a diuron-degrading community to diuron exposure assessed by real-time
      quantitative PCR monitoring of phenylurea hydrolase A and B encoding genes.
AB  - A real-time quantitative PCR method was developed to detect and quantify
      phenlylurea hydrolase genes' (puhA and puhB) sequences from environmental DNA
      samples to assess diuron-degrading genetic potential in some soil and sediment
      microbial communities. In the soil communities, mineralization rates (determined
      with [ring-14C]-labeled diuron) were linked to diuron-degrading genetic
      potentials estimated from puhB number copies, which increased following repeated
      diuron treatments. In the sediment communities, mineralization potential did not
      depend solely on the quantity of puhB copies, underlining the need to assess gene
      expression. In the sediment samples, both puhB copy numbers and mineralization
      capacities were highly conditioned by whether or not diuron-treated soil was
      added. This points to transfers of degradative potential from soils to sediments.
      No puhA gene was detected in soil and sediment DNA extracts. Moreover, some
      sediments exhibited high diuron mineralization potential even though puhB genes
      were not detected, suggesting the existence of alternative diuron degradation
      pathways.

PMID- 22854896
TI  - Relationship between severity of shoulder subluxation and soft-tissue injury in
      hemiplegic stroke patients.
AB  - OBJECTIVE: The aims of this study were: (i) to determine whether the severity of
      post-hemiplegic shoulder subluxation in stroke patients correlates with soft
      tissue injury; and (ii) to determine the shoulder subluxation measurement cut-off
      points that are indications for further ultrasound examination for soft-tissue
      injuries in these patients. DESIGN: Cross-sectional study. PATIENTS: A total of
      39 stroke patients with shoulder subluxation. METHODS: Shoulder subluxation was
      evaluated by physical examination, radiography and ultrasound. Soft-tissue
      injuries were assessed by ultrasound. Subluxation parameters were entered into
      stepwise logistic regression analyses to predict biceps and supraspinatus
      tendonitis. With the assumption that shoulder subluxation can be a predisposing
      factor for tendonitis, receiver operating characteristic curves for shoulder
      subluxation parameters of the affected side were used to determine cut-off points
      for optimal sensitivity and specificity of biceps and supraspinatus tendonitis.
      RESULTS: Shoulder subluxation lateral distance, measured by physical examination,
      is a predictor for supraspinatus tendonitis (odds ratio = 34.9, p = 0.036).
      Further ultrasound investigation for soft-tissue injury is indicated when
      subluxation lateral distance, measured by physical examination is >= 2.25 cm or,
      measured by radiographic examination, >= 3.18 cm for lateral distance, >= 3.08 cm
      for vertical distance, or >= 2.65 cm for horizontal distance. CONCLUSION: When
      post-hemiplegic shoulder subluxation measurements exceed the above-mentioned cut
      off points in physical or radiographic examinations, further ultrasound
      evaluation for soft-tissue injury is recommended.

PMID- 22854898
TI  - A ruthenium(II) complex with environment-responsive dual emission and its
      application in the detection of cysteine/homocysteine.
AB  - A ruthenium polypyridine complex [Ru(phen)(2)(IPBA)](PF(6))(2) (complex 1) (IPBA
      = 4-(1H-imidazo[4,5-f][1,9]phenanthroline-2-yl)benzaldehyde), which displays
      environment-responsive dual emissive properties, was designed and synthesized. In
      aprotic solvent, such as DMSO, DMF or CH(3)CN, the complex emits strong cyan
      light. When in protic solvent, it emits orange light. Similarly, the response of
      the complex to homocysteine and cysteine (Hcy/Cys) also shows obvious solvent
      dependence. TDDFT calculations reveal that the protonation of imidazole nitrogen
      in protic solution is responsible for the luminescent red shift. Hence, the
      complex could be used to detect Hcy/Cys in aprotic solvent, as well as in protic
      solvent.

PMID- 22854899
TI  - Bioconjugation of luminescent silicon quantum dots to gadolinium ions for
      bioimaging applications.
AB  - Luminescent imaging agents and MRI contrast agents are desirable components in
      the rational design of multifunctional nanoconstructs for biological imaging
      applications. Luminescent biocompatible silicon quantum dots (SiQDs) and
      gadolinium chelates can be applied for fluorescence microscopy and MRI,
      respectively. Here, we report the first synthesis of a nanocomplex incorporating
      SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct
      is composed of a PEGylated micelle, with hydrophobic SiQDs in its core,
      covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius
      of 85 nm for these nanoconstructs, which is consistent with the electron
      microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of
      the probes verified that they maintain their optical properties within the
      intracellular environment. The magnetic resonance relaxivity of the nanoconstruct
      was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000
      mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of
      the newly developed probe open the door for use of SiQDs in future multimodal
      applications such as tumour imaging.

PMID- 22854900
TI  - A comparison of manual and quantitative elbow strength testing.
AB  - OBJECTIVE: The aim of this study was to compare the clinical ratings of elbow
      strength obtained by skilled clinicians with objective strength measurement
      obtained through quantitative testing. DESIGN: A retrospective comparison of
      subject clinical records with quantitative strength testing results in a motion
      analysis laboratory was conducted. A total of 110 individuals between the ages of
      8 and 65 yrs with traumatic brachial plexus injuries were identified. Patients
      underwent manual muscle strength testing as assessed on the 5-point British
      Medical Research Council Scale (5/5, normal; 0/5, absent) and quantitative elbow
      flexion and extension strength measurements. RESULTS: A total of 92 subjects had
      elbow flexion testing. Half of the subjects clinically assessed as having normal
      (5/5) elbow flexion strength on manual muscle testing exhibited less than 42% of
      their age-expected strength on quantitative testing. Eighty-four subjects had
      elbow extension strength testing. Similarly, half of those displaying normal
      elbow extension strength on manual muscle testing were found to have less than
      62% of their age-expected values on quantitative testing. Significant differences
      between manual muscle testing and quantitative findings were not detected for the
      lesser (0-4) strength grades. CONCLUSIONS: Manual muscle testing, even when
      performed by experienced clinicians, may be more misleading than expected for
      subjects graded as having normal (5/5) strength. Manual muscle testing estimates
      for the lesser strength grades (1-4/5) seem reasonably accurate.

PMID- 22854901
TI  - Efficacy of early treatment with carbamazepine in prevention of neuropathic pain
      in patients with spinal cord injury.
AB  - OBJECTIVE: The aim of this study was to evaluate whether early treatment with
      carbamazepine decreases the incidence of neuropathic pain (NP) or its intensity
      in patients with spinal cord injury. DESIGN: This study was a randomized, double
      blind, placebo-controlled clinical trial at a third-level university hospital
      involving patients older than 18 yrs with a diagnosis of spinal cord injury
      sustained within 2 wks before enrollment and without evidence of NP. The patients
      received either carbamazepine up to 600 mg/day or placebo for 1 mo. Pain
      intensity was measured with a 10-cm visual analog scale and the SF-36 bodily pain
      subscale; quality-of-life, with the Short Form 36 (SF-36) Scale; and depression,
      with the Zung Self-Rating Depression Scale. Measurements were carried out at the
      start of the randomized trial and at the 1-, 3-, and 6-month follow-up
      assessments. RESULTS: Twenty-one of 46 patients developed NP. At the 1-, 3-, and
      6-month follow-up assessments, NP was present in 4, 11, and 10 patients of the
      carbamazepine group and in 8, 9, and 8 patients of the placebo group,
      respectively. At 1 mo, two patients in the carbamazepine group vs. eight patients
      in the placebo group reported moderate/intense pain (visual analog scale, >=4.0;
      P = 0.024). At the 3- and 6-month follow-up appointments, moderate/intense pain
      was reported by eight vs. six (P = 0.498) and six vs. eight patients (P = 0.298),
      carbamazepine and placebo group, respectively. There was no difference in the
      depression ratings or in any of the SF-36 scales. CONCLUSIONS: Early intervention
      with carbamazepine decreased NP incidence at the 1-month but not at the 3- and 6
      month follow-ups in the group of patients with acquired spinal cord injury.

PMID- 22854902
TI  - Long-term lifestyle intervention with optimized high-intensity interval training
      improves body composition, cardiometabolic risk, and exercise parameters in
      patients with abdominal obesity.
AB  - OBJECTIVE: The aim of this study was to study the impact of a combined long-term
      lifestyle and high-intensity interval training intervention on body composition,
      cardiometabolic risk, and exercise tolerance in overweight and obese subjects.
      DESIGN: Sixty-two overweight and obese subjects (53.3 +/- 9.7 yrs; mean body mass
      index, 35.8 +/- 5 kg/m(2)) were retrospectively identified at their entry into a
      9-mo program consisting of individualized nutritional counselling, optimized high
      intensity interval exercise, and resistance training two to three times a week.
      Anthropometric measurements, cardiometabolic risk factors, and exercise tolerance
      were measured at baseline and program completion. RESULTS: Adherence rate was
      97%, and no adverse events occurred with high-intensity interval exercise
      training. Exercise training was associated with a weekly energy expenditure of
      1582 +/- 284 kcal. Clinically and statistically significant improvements were
      observed for body mass (-5.3 +/- 5.2 kg), body mass index (-1.9 +/- 1.9 kg/m(2)),
      waist circumference (-5.8 +/- 5.4 cm), and maximal exercise capacity (+1.26 +/-
      0.84 metabolic equivalents) (P < 0.0001 for all parameters). Total fat mass and
      trunk fat mass, lipid profile, and triglyceride/high-density lipoprotein ratio
      were also significantly improved (P < 0.0001). At program completion, the
      prevalence of metabolic syndrome was reduced by 32.5% (P < 0.05). Independent
      predictors of being a responder to body mass and waist circumference loss were
      baseline body mass index and resting metabolic rate; those for body mass index
      decrease were baseline waist circumference and triglyceride/high-density
      lipoprotein cholesterol ratio. CONCLUSIONS: A long-term lifestyle intervention
      with optimized high-intensity interval exercise improves body composition,
      cardiometabolic risk, and exercise tolerance in obese subjects. This intervention
      seems safe, efficient, and well tolerated and could improve adherence to exercise
      training in this population.

PMID- 22854903
TI  - Efficacy of combined atorvastatin and sildenafil in promoting recovery after
      ischemic stroke in mice.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that a combination of
      atorvastatin and sildenafil promotes recovery in an additive manner after
      ischemic stroke in mice. DESIGN: Adult C57BL/6 mice (n = 67) were subjected to
      transient middle cerebral artery occlusion. Vehicle-control (H2O), atorvastatin
      (0.3 mg/kg), sildenafil (0.3 mg/kg), or combined atorvastatin (0.3 mg/kg) and
      sildenafil (0.3 mg/kg) were administrated via oral gavage daily for 6 days
      starting 24 hrs after ischemia. Behavioral studies including neurologic score and
      adhesive removal test were performed before surgery and on postoperative days 1
      and 7; cylinder test was performed before surgery and on postoperative day 7.
      Mice were killed after 7 days and brain slices were stained with hematoxylin and
      eosin to measure the infarct volume. RESULTS: The combination group performed
      significantly better in the adhesive removal test (mean +/- SD) (50 +/- 54 secs)
      as compared with the control group (147 +/- 109 secs) (P < 0.05) and to
      atorvastatin (144 +/- 102 secs) (P < 0.05) but did not show statistically
      significant improvement as compared with sildenafil (107 +/- 115 secs) (P =
      0.148). There were no significant differences among the groups in neurologic
      score and cylinder test. There was no significant difference in the infarct
      volume. CONCLUSIONS: The data suggest that combined atorvastatin and sildenafil
      generates a better functional outcome as compared with atorvastatin-only
      treatment, but not sildenafil-only treatment, in one of multiple variables
      tested.

PMID- 22854904
TI  - Quadriceps muscle atrophy after anterior cruciate ligament transection involves
      increased mRNA levels of atrogin-1, muscle ring finger 1, and myostatin.
AB  - OBJECTIVE: The aim of this study was to assess the mRNA levels of atrogin-1,
      muscle ring finger 1, and myostatin in rat quadriceps after anterior cruciate
      ligament (ACL) transection. DESIGN: Wistar rats were randomized into three
      different groups: ACL (surgery and ACL transection), sham (surgery without ACL
      transection), and control. Vastus medialis, rectus femoris, and vastus lateralis
      muscles were harvested at 1, 2, 3, 7, and 15 days after ACL transection. The mRNA
      levels of atrogin-1, muscle ring finger 1, and myostatin, as well as the
      ubiquitinated protein content, muscle mass, and cross-sectional area of the
      muscle fibers, were evaluated. RESULTS: Elevated levels of atrogin-1, muscle ring
      finger 1, and myostatin mRNA were detected in all tested muscles at most time
      points. The ubiquitinated protein content was increased at 3 days in the ACL and
      sham groups. The muscle mass of the ACL group was reduced at 3, 7, and 15 days
      (vastus lateralis and vastus medialis) and at 7 and 15 days (rectus femoris),
      whereas it was reduced in the sham group at 3 and 7 days (vastus lateralis and
      vastus medialis) and at 7 days (rectus femoris). The cross-sectional area of
      vastus medialis was reduced at 3, 7, and 15 days in the ACL group and at 3 and 7
      days in the sham group. The cross-sectional area of the vastus lateralis was
      reduced at 7 and 15 days in the ACL group and at 7 days in the sham group.
      Whereas muscle mass and cross-sectional area recovery was noted in the sham
      group, no recovery was observed in the ACL group. CONCLUSIONS: Quadriceps atrophy
      after ACL transection involves increased levels of myostatin, atrogin-1, and
      muscle ring finger 1 mRNA and the accumulation of ubiquitinated protein.

PMID- 22854905
TI  - Comparison of day rehabilitation to skilled nursing facility for the
      rehabilitation for total knee arthroplasty.
AB  - OBJECTIVES: Day rehabilitation (DR) is emerging in the United States as an
      alternative postacute rehabilitation setting. There have been no published
      studies focused on the efficacy of DR for a postacute orthopedic population. This
      study investigated the efficacy of DR as an alternative to inpatient skilled
      nursing facility (SNF) status post total knee arthroplasty. DESIGN: A
      retrospective chart review was conducted. Subjects were 50-75 yrs old, underwent
      total knee arthroplasty in 2009, and were discharged from an SNF or DR affiliated
      with a postacute healthcare system. The sample consisted of all DR (n = 56) and
      randomly selected SNF (n = 45) subjects. RESULTS: Upon admission, there were no
      differences between DR and SNF groups for age, sex, comorbidity score, pain
      score, knee range of motion, ambulation distance, locomotion Functional
      Independent Measure score, or body mass index. Upon discharge, there was no
      difference in knee range of motion or pain between groups. Discharge ambulation
      distance (P = 0.000) and locomotion Functional Independent Measure score (P =
      0.001) were greater for the DR compared with the SNF group. Cost was lower (P =
      0.000) and length of stay was shorter (P = 0.000) for the DR compared with the
      SNF group. CONCLUSIONS: Subjects discharged from DR had similar or improved
      outcomes compared with subjects discharged from SNF at a lower cost and shorter
      stay. Results suggest that DR delivered significant cost savings when compared
      with SNF without compromising patient outcomes.

PMID- 22854906
TI  - Cone-shaped epiphysis.

PMID- 22854907
TI  - Implementing a multidimensional geriatric curriculum in a physical medicine and
      rehabilitation residency program.
AB  - Residency training in physical medicine and rehabilitation may not contain a
      formal curriculum in geriatric patient care. A multidimensional geriatric
      curriculum to third and fourth year physical medicine and rehabilitation
      residents was implemented to enhance their knowledge in and attitude toward
      geriatrics. The curriculum consisted of a 12-wk clinical rotation at various
      sites of geriatric care including outpatient geriatric clinic, skilled nursing
      facility, continuing care retirement community, and home visits. Six online self
      learning modules and multiple didactic sessions were also created. The residents'
      knowledge and attitude were assessed by pretest and posttest design using the
      Geriatric Knowledge Test, the Geriatric Attitude Scale, and the Attitudes Toward
      Teamwork in Healthcare Scale. In addition, the residents completed rotation
      evaluations to rate their learning experiences. Ten postgraduate year 3 and 4
      physical medicine and rehabilitation residents participated in the geriatric
      curriculum, which included a required rotation. The Geriatric Knowledge Test
      score at baseline was 67.2%. With the completion of the curriculum, the Geriatric
      Knowledge Test scores showed improvement to 72.7%, although not statistically
      significant. The residents showed more favorable attitudes toward the geriatric
      population and interdisciplinary teamwork as measured by the Geriatric Attitude
      Scale and the Attitudes Toward Teamwork in Healthcare Scale. Overall, they rated
      the learning experiences highly on a 1-9 rating scale, with 9 being the highest
      rating; the residents assigned an average rating of 7.06 to specific learning
      activities within the rotation and an average rating of 6.89 to the
      organizational aspects of the rotation itself. The implementation of this
      geriatric curriculum allowed for improved geriatric training in physical medicine
      and rehabilitation residents.

PMID- 22854908
TI  - The relationship of the energetic cost of slow walking and peak energy
      expenditure to gait speed in mid-to-late life.
AB  - OBJECTIVE: Peak energy expenditure is highly correlated with usual gait speed;
      however, it is unknown whether the energetic cost of walking is also an important
      contributor to usual gait speed when considered as a component of peak walking
      capacity. DESIGN: The energetic cost of 5 mins of slow treadmill walking (0.67
      m/sec), peak overground walking energy expenditure, and usual gait speed over 6 m
      were assessed cross-sectionally in 405 adults aged 33 to 94 yrs in the Baltimore
      Longitudinal Study of Aging. RESULTS: Mean (SD) energy expenditures during slow
      and peak sustained walking were 8.9 (1.4) and 18.38 (4.8) ml kg(-1) min(-1),
      respectively. Overall, the energetic cost of slow walking as a percentage of peak
      walking energy expenditure was strongly associated with usual gait speed (P <
      0.001); however in stratified analyses, this association was maintained only in
      those with peak walking capacity below 18.3 ml kg(-1) min(-1) (P = 0.04), the
      threshold associated with independent living. CONCLUSIONS: In older persons with
      substantially reduced peak walking capacity, the energetic cost of walking is
      associated with gait speed, particularly when peak walking capacity nears the
      minimum level considered necessary for independent living. Thus, optimal
      habilitation in older frail persons may benefit from both improving fitness and
      reducing the energetic cost of walking.

PMID- 22854909
TI  - Kambin triangle versus the supraneural approach for the treatment of lumbar
      radicular pain.
AB  - OBJECTIVE: The aim of this study was to conduct a randomized, blinded,
      prospective outcome study on the short-term benefits of the Kambin triangle vs.
      the supraneural approach for the treatment of lumbar radicular pain. DESIGN:
      Subjects with lumbar radicular pain (n = 100) were randomly assigned to undergo
      transforaminal epidural steroid injection using either the Kambin triangle
      approach or the supraneural approach. Primary outcomes were measured with a
      verbal numeric pain scale and the Oswestry Disability Index, and the results at 2
      and 12 wks after the procedure were compared between the groups. Secondary
      outcomes included patient satisfaction and the incidence of complications during
      the transforaminal epidural steroid injection procedure. RESULTS: For both
      groups, the verbal numeric pain scale and Oswestry Disability Index scores
      improved 2 wks after the injections, and this improvement was maintained through
      the 12-wk follow-up. The verbal numeric pain scale, Oswestry Disability Index,
      and effectiveness scores were not significantly different between groups. Neural
      contact occurred in nine cases with the supraneural approach; no patients
      experienced neural contact with the Kambin triangle approach. CONCLUSIONS: The
      Kambin triangle approach can be used instead of the supraneural approach in cases
      where it is difficult to place the needle at the anterior epidural space.

PMID- 22854910
TI  - Relationship between body mass index and rehabilitation outcomes in chronic
      stroke.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between body
      mass index (BMI) and change in motor impairment and functional mobility after a
      gait rehabilitation intervention in chronic stroke subjects. DESIGN: Correlation
      and linear regression analyses of pretreatment and end-of-treatment Fugl-Meyer
      scores and modified Emory Functional Ambulation Profile scores from hemiparetic
      subjects (n = 108, >3 mos post stroke) who participated in a randomized
      controlled trial comparing two 12-wk ambulation training treatments were
      generated. RESULTS: A series of linear regression models that controlled for age,
      sex, stroke type, interval post-stroke, and training device found the change in
      the Fugl-Meyer score to be significantly negatively associated with pretreatment
      BMI (beta = -0.207, P = 0.036) and the change in the "up and go" modified Emory
      Functional Ambulation Profile score to be significantly positively associated
      with BMI (beta = 0.216, P = 0.03). Changes in modified Emory Functional
      Ambulation Profile scores in floor, carpet, obstacles, or stair climbing were not
      significantly associated with BMI. CONCLUSIONS: Chronic stroke subjects with a
      higher BMI were less likely to demonstrate improvement in motor impairment and up
      and go functional mobility performance in response to ambulation training,
      irrespective of treatment intervention. Stroke rehabilitation clinicians should
      consider BMI when formulating rehabilitation goals. Further studies are necessary
      to determine whether obesity is a predictor of longer-term post-stroke motor and
      functional recovery.

PMID- 22854911
TI  - Therapeutic effects of lidocaine patch on myofascial pain syndrome of the upper
      trapezius: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: The aim of this study was to compare topical 5% lidocaine patch with
      placebo patch in the treatment of myofascial pain syndrome of the upper
      trapezius. DESIGN: In this prospective, randomized, double-blind, placebo
      controlled study, 60 participants were randomly assigned, placing 31 subjects in
      the 5% lidocaine patch group and 29 subjects in the placebo patch group. We used
      the Verbal Rating Scale (VRS), the Pressure Pain Threshold, the ranges of motion
      of the neck, and the Neck Disability Index to evaluate the subjective pain
      intensity, objective pain intensity, ranges of motion, and disability of the
      neck, respectively. Outcome measures were performed before (day 0) the treatment
      course, 12 hrs after removal of the final patch on the seventh day (day 7), and 1
      wk (day 14) and 3 wks (day 28) after the completion of treatment course. RESULTS:
      The characteristics of the participants did not differ at baseline. Pain
      intensity assessed by the VRS decreased at day 7 in both the lidocaine patch and
      placebo patch groups. There was no significant difference between the two groups
      in the VRS, the Pressure Pain Threshold, the ranges of motion, and the Neck
      Disability Index. At day 14, the experimental group continued to improve in the
      VRS (1.06), but the pain of the placebo group aggravated (VRS, 1.5). The
      difference is significant (P = 0.03). In addition, the Neck Disability Index in
      the lidocaine patch group decreased significantly as compared to that in the
      placebo group. The pain-relieving effect of the lidocaine patch attenuated, and
      it was not significantly different between the two groups at day 28 in the VRS
      and the Neck Disability Index. Neither the Pressure Pain Threshold nor the ranges
      of motion were significantly different through the periods of this study.
      CONCLUSIONS: The application of the 5% lidocaine patch is probably superior to
      the placebo patch in relieving pain and in reducing associated neck disability
      for a period of longer than 1 wk for treating patients with myofascial pain
      syndrome of the upper trapezius.

PMID- 22854912
TI  - Peripheral arterial disease masquerading as low back pain.

PMID- 22854914
TI  - Base- and metal-free C-H direct arylations of naphthalene and other unbiased
      arenes with diaryliodonium salts.
AB  - A novel metal-free direct arylation of unbiased arenes with diaryliodonium
      triflates in a process where the use of solvents and additives is not required
      has been established.

PMID- 22854913
TI  - Epithelial machines of morphogenesis and their potential application in organ
      assembly and tissue engineering.
AB  - Sheets of embryonic epithelial cells coordinate their efforts to create diverse
      tissue structures such as pits, grooves, tubes, and capsules that lead to organ
      formation. Such cells can use a number of cell behaviors including contractility,
      proliferation, and directed movement to create these structures. By contrast,
      tissue engineers and researchers in regenerative medicine seeking to produce
      organs for repair or replacement therapy can combine cells with synthetic
      polymeric scaffolds. Tissue engineers try to achieve these goals by shaping
      scaffold geometry in such a way that cells embedded within these scaffold self
      assemble to form a tissue, for instance aligning to synthetic fibers, and
      assembling native extracellular matrix to form the desired tissue-like structure.
      Although self-assembly is a dominant process that guides tissue assembly both
      within the embryo and within artificial tissue constructs, we know little about
      these critical processes. Here, we compare and contrast strategies of tissue
      assembly used by embryos to those used by engineers during epithelial
      morphogenesis and highlight opportunities for future applications of
      developmental biology in the field of tissue engineering.

PMID- 22854916
TI  - The effect of insulin resistance on postprandial triglycerides in Korean type 2
      diabetic patients.
AB  - We hypothesized that the influence of metabolic parameters depends on metabolic
      syndrome (MetS) status. The clinical and metabolic implications of postprandial
      triglyceride (ppTG) in Korean type 2 diabetes were investigated in the presence
      or absence of MetS, MetS+, or MetS-. To investigate the relationship between ppTG
      and metabolic parameters, we analyzed plasma TG levels in 126 newly diagnosed,
      drug-naive diabetic patients after ingestion of a standardized low calorie and
      fat (500 kcal, 17.5 g fat) liquid meal formula. We report that MetS+ patients
      have significantly higher BMI, waist/hip ratio, HOMA-IR, and HOMA-beta, but
      insignificantly higher fasting TG, ppTG, and DeltaTG than MetS- patients. In the
      MetS+ patients, ppTG correlated with fasting TG and non-HDL, but was not related
      to HOMA-IR. In MetS- patients, ppTG correlated with fasting TG, non-HDL, blood
      pressure, waist/hip ratio, fasting C-peptide and insulin levels, and HOMA-IR.
      Multivariate analysis showed HOMA-IR to be a predictive factor for ppTG in MetS-
      patients but not in MetS+ patients. ppTG correlated with IR in MetS- type 2
      diabetic patients but not in MetS+. This unexpected result implies that MetS+
      diabetic patients already have high fasting TG and that IR influences fasting TG
      more dominantly than ppTG.

PMID- 22854915
TI  - Optofluidic detection for cellular phenotyping.
AB  - Quantitative analysis of the output of processes and molecular interactions
      within a single cell is highly critical to the advancement of accurate disease
      screening and personalized medicine. Optical detection is one of the most broadly
      adapted measurement methods in biological and clinical assays and serves cellular
      phenotyping. Recently, microfluidics has obtained increasing attention due to
      several advantages, such as small sample and reagent volumes, very high
      throughput, and accurate flow control in the spatial and temporal domains.
      Optofluidics, which is the attempt to integrate optics with microfluidics, shows
      great promise to enable on-chip phenotypic measurements with high precision,
      sensitivity, specificity, and simplicity. This paper reviews the most recent
      developments of optofluidic technologies for cellular phenotyping optical
      detection.

PMID- 22854917
TI  - Comment on: acute and chronic fluctuations in blood glucose levels can increase
      oxidative stress in type 2 diabetes mellitus.

PMID- 22854918
TI  - The ability of a new continuous cardiac output monitor to measure trends in
      cardiac output following implementation of a patient information calibration and
      an automated exclusion algorithm.
AB  - A new non-invasive continuous cardiac output (esCCO) monitoring system solely
      utilizing a routine cardiovascular monitor was developed, even though a reference
      cardiac output (CO) is consistently required. Subsequently, a non-invasive
      patient information CO calibration together with a new automated exclusion
      algorithm was implemented in the esCCO system. We evaluated the accuracy and
      trending ability of the new esCCO system. Either operative or postoperative data
      of a multicenter study in Japan for evaluation of the accuracy of the original
      version of esCCO system were used to develop the new esCCO system. A total of 207
      patients, mostly cardiac surgical patients, were enrolled in the study. Data were
      manually reviewed to formulate a new automated exclusion algorithm with enhanced
      accuracy. Then, a new esCCO system based on a patient information calibration
      together with the automated exclusion algorithm was developed. CO measured with a
      new esCCO system was compared with the corresponding intermittent bolus
      thermodilution CO (ICO) utilizing statistical methods including polar plots
      analysis. A total of 465 sets of CO data obtained using the new esCCO system were
      evaluated. The difference in the CO value between the new esCCO and ICO was 0.34
      +/- 1.50 (SD) L/min (95 % confidence limits of -2.60 to 3.28 L/min). The
      percentage error was 69.6 %. Polar plots analysis showed that the mean polar
      angle was -1.6 degrees  and radial limits of agreement were +/-53.3 degrees .
      This study demonstrates that the patient information calibration is clinically
      useful as ICO, but trending ability of the new esCCO system is not clinically
      acceptable as judged by percentage error and polar plots analysis, even though
      it's trending ability is comparable with currently available arterial waveform
      analysis methods.

PMID- 22854919
TI  - Subchondral impaction fractures of the non-weight-bearing portion of the lateral
      femoral condyle.
AB  - OBJECTIVE: To document the first report of intra-articular, non-weight-bearing,
      impaction fractures of the lateral femoral condyle. MATERIALS & METHODS:
      Institutional Review Board and Regional Ethics Committee approval for this study
      was obtained and patient informed consent deemed unnecessary. We prospectively
      documented all potential cases of non-weight-bearing posterior subchondral
      impaction fractures of the femoral condyles diagnosed on magnetic resonance
      imaging (MRI) of the knee performed at our institution between January 2006 and
      December 2011. The cases were reviewed and discussed by three experienced
      musculoskeletal radiologists and only cases satisfying pre-defined MRI criteria
      were included. RESULTS: Sixteen cases of intra-articular impaction fractures in a
      posterior, non-weight-bearing area of the lateral femoral condyle were diagnosed
      in patients with a mean age of 40. Eight were associated with recreational sports
      activities and 4 with repeated kneeling. There were no fractures documented in
      the non-weight-bearing aspect of the medial femoral condyles. Proposed underlying
      mechanisms for development of this type of fracture are presented. CONCLUSION:
      Awareness, along with a high level of suspicion, that non-specific knee pain,
      especially in patients involved in athletic activities, could be due to intra
      articular impaction fractures of the non-weight-bearing posterior aspect of the
      lateral femoral condyle is essential and MRI is the mainstay of diagnosis.

PMID- 22854920
TI  - Posterior-only approach surgery for fixation and decompression of thoracolumbar
      spinal tuberculosis: a retrospective study.
AB  - STUDY DESIGN: A retrospective case study series. OBJECTIVE: To evaluate the
      results of posterior decompression and transpedicular screw fixation in 18 cases
      of thoracolumbar spinal tuberculosis with neurological deficit. SUMMARY OF
      BACKGROUND DATA: Spinal tuberculosis has been managed with various modalities of
      treatment ranging from only antitubercular drugs to radical procedures such as
      anterior or combined approach surgeries. However, although the former method of
      treatment sometimes is met with unacceptable kyphosis, the later is considered to
      be too drastic. In the present study, authors have shown the results of posterior
      decompression and pedicle screw fixation in selected cases of Pott paraplegia.
      METHODS: The cases (12 males and 6 females) were operated with a posterior
      decompression and transpedicular screw fixation in a single stage along with
      antitubercular drug treatment. All of these patients had varying degrees of
      neurological deficit (4 with Frankel grade A, 8 Frankel B, 4 Frankel C, and 2
      Frankel D) and single level involvement with <50% vertebral body destruction and
      mild kyphosis of 8-27 degrees. Short-segment pedicle screw fixation, posterior
      decompression, and correction of kyphosis were performed in single stage.
      RESULTS: Kyphosis improved from preoperative value of 17.7+/-5.8 degrees to 9.4+/
      4.6 degrees postoperatively. At a follow-up period of 24-46 months, final
      kyphosis correction was maintained at 11.6+/-5.4 degrees. Bony fusion was
      achieved in 55.5% cases. Neurological recovery occurred in 17 patients (94.4%).
      All patients became pain free, with final visual analogue score 0-2. CONCLUSIONS:
      The procedure in safe and has satisfactory results in early active cases of Pott
      paraplegia with less destruction of vertebral bodies.

PMID- 22854921
TI  - Monitoring image guidance system accuracy during spinal surgery with mini-screw
      fiducials: technical note.
AB  - STUDY DESIGN: A technical note. OBJECTIVE: To describe a technique for measuring
      accuracy of intraoperative image guidance systems in spine surgery. SUMMARY OF
      BACKGROUND DATA: Image guidance may be of use when performing complex procedures
      on the spine. However, as the operation progresses and, in particular, once any
      deformity has been corrected, the image guidance system may become unreliable. In
      practice, this often results in repeated image acquisitions thus increasing the
      radiation exposure to the patient. METHODS: Small titanium, cranio-facial screws
      were placed on the dorsal aspect of the spine intraoperatively, before the
      acquisition of images and used as fiducials. RESULTS: The authors were able to
      accurately discern the true precision of the image guidance system used with an
      intraoperative computed tomography scanner, throughout the procedure.
      CONCLUSIONS: By using intraoperatively placed mini-screw fiducials, the surgeon
      may check and quantify the underlying system accuracy both initially and
      throughout the surgery. In the future, "auto-adjust" functions may be integrated
      into the computer software to automatically recalibrate the system when a probe
      is placed into the fiducials without the need for rescanning.

PMID- 22854922
TI  - Recurrent postpartum impetigo herpetiformis presenting after a "skip" pregnancy.

PMID- 22854923
TI  - Cadmium and lead concentrations in the fish tissues of a coastal lagoon system of
      the SE Gulf of California.
AB  - Mean Cd trend in the muscle of omnivorous (O), planktivorous (P), benthopelagic
      carnivorous (BPC), and benthic carnivorous (BC) fish of one lagoon of NW Mexico
      was BPC > BC > P > O (0.89, 0.59, 0.55 and 0.24 MUg g(-1)). That of Pb was P > BC
      > O > BPC (1.07, 0.48, 0.17 and 0.04 MUg g(-1)). In the liver Cd was P > BPC > O
      > BC (5.09, 2.40, 2.07 and 1.95 MUg g(-1)). Pb was P > O > BPC > BC (0.63, 0.40,
      0.13 and 0.07 MUg g(-1)). There were no differences in Cd and Pb contents due to
      feeding habits, and the correlations between metals and troph level were not
      significant (p > 0.05 in all cases).

PMID- 22854924
TI  - Taking note of over-the-counter remedies for adolescents with cannabis
      dependence.

PMID- 22854925
TI  - Metformin as a treatment for antipsychotic drug side effects: special focus on
      women with schizophrenia.

PMID- 22854926
TI  - Relation of childhood malnutrition to adult mental disorders.

PMID- 22854927
TI  - The highs and lows of amygdala reactivity in bipolar disorders.

PMID- 22854928
TI  - Launch of mental health support to the Fukushima Daiichi nuclear power plant
      workers.

PMID- 22854929
TI  - Designing case-control studies: decisions about the controls.
AB  - The authors quantified, first, the effect of misclassified controls (i.e.,
      individuals who are affected with the disease under study but who are classified
      as controls) on the ability of a case-control study to detect an association
      between a disease and a genetic marker, and second, the effect of leaving
      misclassified controls in the study, as opposed to removing them (thus decreasing
      sample size). The authors developed an informativeness measure of a study's
      ability to identify real differences between cases and controls. They then
      examined this measure's behavior when there are no misclassified controls, when
      there are misclassified controls, and when there were misclassified controls but
      they have been removed from the study. The results show that if, for example, 10%
      of controls are misclassified, the study's informativeness is reduced to
      approximately 81% of what it would have been in a sample with no misclassified
      controls, whereas if these misclassified controls are removed from the study, the
      informativeness is only reduced to about 90%, despite the reduced sample size. If
      25% are misclassified, those figures become approximately 56% and 75%,
      respectively. Thus, leaving the misclassified controls in the control sample is
      worse than removing them altogether. Finally, the authors illustrate how
      insufficient power is not necessarily circumvented by having an unlimited number
      of controls. The formulas provided by the authors enable investigators to make
      rational decisions about removing misclassified controls or leaving them in.

PMID- 22854930
TI  - Increased amygdala responses to sad but not fearful faces in major depression:
      relation to mood state and pharmacological treatment.
AB  - OBJECTIVE: Increased amygdala response to negative emotions seen in functional
      MRI (fMRI) has been proposed as a biomarker for negative emotion processing bias
      underlying depressive symptoms and vulnerability to depressive relapse that are
      normalized by antidepressant drug treatment. The purpose of this study was to
      determine whether abnormal amygdala responses to face emotions in depression are
      related to specific emotions or change in response to antidepressant treatment
      and whether they are present as a stable trait in medication-free patients in
      remission. METHOD: Sixty-two medication-free unipolar depressed patients (38 were
      currently depressed, and 24 were in remission) and 54 healthy comparison subjects
      underwent an indirect face-emotion processing task during fMRI. Thirty-two
      currently depressed patients were treated with the antidepressant citalopram for
      8 weeks. Adherence to treatment was evaluated by measuring citalopram plasma
      concentrations. RESULTS: Patients with current depression had increased bilateral
      amygdala responses specific to sad faces relative to healthy comparison subjects
      and nonmedicated patients in stable remission. Treatment with citalopram
      abolished the abnormal amygdala responses to sad faces in currently depressed
      patients but did not alter responses to fearful faces. CONCLUSIONS: Aberrant
      amygdala activation in response to sad facial emotions is specific to the
      depressed state and is a potential biomarker for a negative affective bias during
      a depressive episode.

PMID- 22854931
TI  - Acute clinical deterioration with increased systemic inflammation as a risk
      factor for depression: an alternative interpretation of the data.

PMID- 22854933
TI  - Long-term maintenance with intramuscular ketamine for treatment-resistant bipolar
      II depression.

PMID- 22854940
TI  - Treatment of gender identity disorder.

PMID- 22854953
TI  - Hepatic hemangiopericytoma/solitary fibrous tumor: a review of our current
      understanding and case study.
AB  - INTRODUCTION: In 2002, the World Health Organization reclassified the soft tissue
      tumors known as hemangiopericytoma (HPC) as a variant of solitary fibrous tumor
      (SFT). As this classification system is still debated and has not been
      universally applied, the following account will provide an updated review of our
      understanding of those tumors still classified as HPC in the literature with
      special emphasis on hepatic HPC/SFT. HPC is a soft tissue neoplasm of mesenchymal
      origin first described by Stout and Murray in 1942. HPC constitutes 1 % of all
      vascular neoplasms and has been thought to coexist with trauma, prolonged steroid
      use, and hypertension. CLINICAL OVERVIEW: Although its presentation may be
      variable, intrahepatic HPC often presents with the patient's increasing awareness
      of a painless mass. Marked hypoglycemia may also accompany the neoplasm. Recent
      evidence suggests that uncontrolled growth may result from a loss of imprinting
      with overproduction of IGF-II in addition to alternative promoter usage.
      Diagnostic modalities including imaging, biopsy, and biochemical assays may be
      used to detect the presence of HPC. As most lesions are benign and slow growing,
      the prognosis is relatively favorable with 10-year survival between 54 and 70 %.
      MANAGEMENT: Current mainstays of treatment include hepatic resection when
      possible especially with the use of adjuvant radiotherapy. Chemotherapeutic
      approaches have been poorly studied and are generally reserved for inoperable
      cases. Antiangiogenic compounds such as temozolomide and bevacizumab provide an
      exciting avenue of treatment. Finally, a case study will be reviewed highlighting
      diagnosis, treatment, and spectrum nature of hepatic HPC.

PMID- 22854954
TI  - Preliminary experience of fast-track surgery combined with laparoscopy-assisted
      radical distal gastrectomy for gastric cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of
      fast-track surgery combined with laparoscopy-assisted radical distal gastrectomy
      for gastric cancer. METHODS: Eighty-eight eligible patients were randomly
      assigned into four groups: (1) fast-track surgery (FTS) + laparoscopy-assisted
      radical distal gastrectomy (LADG), treated with LADG and FTS treatment; (2) LADG,
      treated with LADG and traditional treatment; (3) FTS + open distal grastectomy
      (ODG), treated with ODG and FTS treatment; and (4) ODG, treated with ODG and
      traditional treatment. The clinical parameters and serum indicators were
      compared. RESULTS: Compared with the ODG group, the other three groups had
      earlier first flatus and shorter postoperative hospital stay (all P <0.01; all P
      <0.05), especially in the FTS + LADG group. The level of ALB was higher in the
      FTS + LADG group than in the LADG group at 4 and 7 days after surgery (P <0.05, P
      <0.01). The level of CRP in the FTS + LADG group was lower than in the FTS+ODG
      group at 4 and 7 days after surgery (P <0.05, P <0.05). The FTS + ODG group had
      lowest medical costs. CONCLUSION: Combination of FTS and LADG in gastric cancer
      is safe, feasible, and efficient and can improve nutritional status, lessen
      postoperative stress, and accelerate postoperative rehabilitation. Compared with
      FTS + ODG and LADG, its advantages were limited in short-term follow-up.

PMID- 22854955
TI  - Alternative modes of binding of poly(ADP-ribose) polymerase 1 to free DNA and
      nucleosomes.
AB  - Poly(ADP-ribose) polymerase 1 (PARP-1) is an abundant nuclear protein that binds
      chromatin and catalyzes the transfer of ADP-ribose groups to itself and to
      numerous target proteins upon interacting with damaged DNA. The molecular basis
      for the dual role of PARP-1 as a chromatin architectural protein and a first
      responder in DNA repair pathways remains unclear. Here, we quantified the
      interactions of full-length PARP-1 and its N-terminal half with different types
      of DNA damage and with defined nucleosome substrates. We found that full-length
      PARP-1 prefers nucleosomes with two linker DNA extensions over any other
      substrate (including several free DNA models) and that the C-terminal half of
      PARP-1 is necessary for this selectivity. We also measured the ability of various
      substrates to activate PARP-1 activity and found that the most important feature
      for activation is one free DNA end rather than tight interaction with the
      activating nucleic acid. Our data provide insight into the different modes of
      interaction of this multidomain protein with nucleosomes and free DNA.

PMID- 22854956
TI  - Cystathionine protects against endoplasmic reticulum stress-induced lipid
      accumulation, tissue injury, and apoptotic cell death.
AB  - Cystathionine (R-S-(2-amino-2-carboxyethyl)-l-homocysteine) is a non
      proteinogenic thioether containing amino acid. In mammals, cystathionine is
      formed as an intermediate of the transsulfuration pathway by the condensation of
      serine and homocysteine (Hcy) in a reaction catalyzed by cystathionine beta
      synthase (CBS). Cystathionine is subsequently converted to cysteine plus ammonia
      and alpha-ketobutyrate by the action of cystathionine gamma-lyase (CGL).
      Pathogenic mutations in CBS result in CBS-deficient homocystinuria (HCU) which,
      if untreated, results in mental retardation, thromboembolic complications and
      connective tissue disorders. Currently there is no known function for
      cystathionine other than serving as an intermediate in transsulfuration and to
      date, the possible contribution of the abolition of cystathionine synthesis to
      pathogenesis in HCU has not been investigated. Using both mouse and cell-culture
      models, we have found that cystathionine is capable of blocking the induction of
      hepatic steatosis and kidney injury, acute tubular necrosis, and apoptotic cell
      death by the endoplasmic reticulum stress inducing agent tunicamycin. Northern
      and Western blotting analysis indicate that the protective effects of
      cystathionine occur without any obvious alteration of the induction of the
      unfolded protein response. Our data constitute the first experimental evidence
      that the abolition of cystathionine synthesis may contribute to the pathology of
      HCU and that this compound has therapeutic potential for disease states where ER
      stress is implicated as a primary initiating pathogenic factor.

PMID- 22854957
TI  - Ablation of vacuole protein sorting 18 (Vps18) gene leads to neurodegeneration
      and impaired neuronal migration by disrupting multiple vesicle transport pathways
      to lysosomes.
AB  - Intracellular vesicle transport pathways are critical for neuronal survival and
      central nervous system development. The Vps-C complex regulates multiple vesicle
      transport pathways to the lysosome in lower organisms. However, little is known
      regarding its physiological function in mammals. We deleted Vps18, a central
      member of Vps-C core complex, in neural cells by generating Vps18(F/F); Nestin
      Cre mice (Vps18 conditional knock-out mice). These mice displayed severe
      neurodegeneration and neuronal migration defects. Mechanistic studies revealed
      that Vps18 deficiency caused neurodegeneration by blocking multiple vesicle
      transport pathways to the lysosome, including autophagy, endocytosis, and
      biosynthetic pathways. Our study also showed that ablation of Vps18 resulted in
      up-regulation of beta1 integrin in mouse brain probably due to lysosome
      dysfunction but had no effects on the reelin pathway, expression of N-cadherin,
      or activation of JNK, which are implicated in the regulation of neuronal
      migration. Finally, we demonstrated that knocking down beta1 integrin partially
      rescued the migration defects, suggesting that Vps18 deficiency-mediated up
      regulation of beta1 integrin may contribute to the defect of neuronal migration
      in the Vps18-deficient brain. Our results demonstrate important roles of Vps18 in
      neuron survival and migration, which are disrupted in multiple neural disorders.

PMID- 22854958
TI  - Znt7-null mice are more susceptible to diet-induced glucose intolerance and
      insulin resistance.
AB  - The Znt7 gene encodes a ubiquitously expressed zinc transporter that is involved
      in transporting cytoplasmic zinc into the Golgi apparatus and a ZnT7-containing
      vesicular compartment. Overexpression of ZnT7 in the pancreatic beta-cell
      stimulates insulin synthesis and secretion through regulation of insulin gene
      transcription. In this study, we demonstrate that ZnT7 is expressed in the mouse
      skeletal muscle. The activity of the insulin signaling pathway was down-regulated
      in myocytes isolated from the femoral muscle of Znt7 knock-out (KO) mice. High
      fat diet consumption (45% kcal) induced weight gain in male Znt7 KO mice but not
      female Znt7 KO mice. Male Znt7 KO mice fed the high fat diet at 5 weeks of age
      for 10 weeks exhibited hyperglycemia in the non-fasting state. Oral glucose
      tolerance tests revealed that male Znt7 KO mice fed the high fat diet had severe
      glucose intolerance. Insulin tolerance tests showed that male Znt7 KO mice were
      insulin-resistant. Diet-induced insulin resistance in male Znt7 KO mice was
      paralleled by a reduction in mRNA expression of Insr, Irs2, and Akt1 in the
      primary skeletal myotubes isolated from the KO mice. Overexpression of ZnT7 in a
      rat skeletal muscle cell line (L6) increased Irs2 mRNA expression, Irs2 and Akt
      phosphorylation, and glucose uptake. We conclude that a combination of decreased
      insulin secretion and increased insulin resistance accounts for the glucose
      intolerance observed in Znt7 KO mice.

PMID- 22854959
TI  - Light chain of factor VIII is sufficient for accelerating cleavage of von
      Willebrand factor by ADAMTS13 metalloprotease.
AB  - We previously demonstrated that coagulation factor VIII (FVIII) accelerates
      proteolytic cleavage of von Willebrand factor (VWF) by A disintegrin and
      metalloprotease with thrombospondin type 1 repeats (ADAMTS13) under fluid shear
      stress. In this study, the structural elements of FVIII required for the rate
      enhancing effect and the biological relevance of this cofactor activity are
      determined using a murine model. An isolated light chain of human FVIII (hFVIII
      LC) increases proteolytic cleavage of VWF by ADAMTS13 under shear in a
      concentration-dependent manner. The maximal rate-enhancing effect of hFVIII-LC is
      ~8-fold, which is comparable with human full-length FVIII and B-domain deleted
      FVIII (hFVIII-BDD). The heavy chain (hFVIII-HC) and the light chain lacking the
      acidic (a3) region (hFVIII-LCDeltaa3) have no effect in accelerating VWF
      proteolysis by ADAMTS13 under the same conditions. Although recombinant hFVIII-HC
      and hFVIII-LCDeltaa3 do not detectably bind immobilized VWF, recombinant hFVIII
      LC binds VWF with high affinity (K(D), ~15 nM). Moreover, ultra-large VWF
      multimers accumulate in the plasma of fVIII(-/-) mice after hydrodynamic
      challenge but not in those reconstituted with either hFVIII-BDD or hFVIII-LC.
      These results suggest that the light chain of FVIII, which is not biologically
      active for clot formation, is sufficient for accelerating proteolytic cleavage of
      VWF by ADAMTS13 under fluid shear stress and (patho) physiological conditions.
      Our findings provide novel insight into the molecular mechanism of how FVIII
      regulates VWF homeostasis.

PMID- 22854960
TI  - Lignan from thyme possesses inhibitory effect on ASIC3 channel current.
AB  - A novel compound was identified in the acidic extract of Thymus armeniacus
      collected in the Lake Sevan region of Armenia. This compound, named "sevanol," to
      our knowledge is the first low molecular weight natural molecule that has a
      reversible inhibition effect on both the transient and the sustained current of
      human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely
      blocked the transient component (IC(50) 353 +/- 23 MUM) and partially (~45%)
      inhibited the amplitude of the sustained component (IC(50) of 234 +/- 53 MUM).
      Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol
      application, except ASIC1a, which showed more than six times less affinity to it
      as compared with the inhibitory action on the ASIC3 channel. To elucidate the
      structure of sevanol, the set of NMR spectra in two solvents (d(6)-DMSO and
      D(2)O) was collected, and the complete chemical structure was confirmed by liquid
      chromatography-mass spectrometry with electrospray ionization (LC-ESI(+)-MS)
      fragmentation. This compound is a new lignan built up of epiphyllic acid and two
      isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1-10
      mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's
      adjuvant injection and reduced response to acid in a writhing test. Thus, we
      assume the probable considerable role of sevanol in known analgesic and anti
      inflammatory properties of thyme.

PMID- 22854961
TI  - N-methyl-D-aspartate receptor- and calpain-mediated proteolytic cleavage of K+-Cl
      cotransporter-2 impairs spinal chloride homeostasis in neuropathic pain.
AB  - Loss of synaptic inhibition by gamma-aminobutyric acid and glycine due to
      potassium chloride cotransporter-2 (KCC2) down-regulation in the spinal cord is a
      critical mechanism of synaptic plasticity in neuropathic pain. Here we present
      novel evidence that peripheral nerve injury diminishes glycine-mediated
      inhibition and induces a depolarizing shift in the reversal potential of glycine
      mediated currents (E(glycine)) in spinal dorsal horn neurons. Blocking glutamate
      N-methyl-D-aspartate (NMDA) receptors normalizes synaptic inhibition, E(glycine),
      and KCC2 by nerve injury. Strikingly, nerve injury increases calcium-dependent
      calpain activity in the spinal cord that in turn causes KCC2 cleavage at the C
      terminus. Inhibiting calpain blocks KCC2 cleavage induced by nerve injury and
      NMDA, thereby normalizing E(glycine). Furthermore, calpain inhibition or
      silencing of MU-calpain at the spinal level reduces neuropathic pain. Thus, nerve
      injury promotes proteolytic cleavage of KCC2 through NMDA receptor-calpain
      activation, resulting in disruption of chloride homeostasis and diminished
      synaptic inhibition in the spinal cord. Targeting calpain may represent a new
      strategy for restoring KCC2 levels and tonic synaptic inhibition and for treating
      chronic neuropathic pain.

PMID- 22854962
TI  - A Polymerase mechanism-based strategy for viral attenuation and vaccine
      development.
AB  - Live, attenuated vaccines have prevented morbidity and mortality associated with
      myriad viral pathogens. Development of live, attenuated vaccines has
      traditionally relied on empirical methods, such as growth in nonhuman cells.
      These approaches require substantial time and expense to identify vaccine
      candidates and to determine their mechanisms of attenuation. With these
      constraints, at least a decade is required for approval of a live, attenuated
      vaccine for use in humans. We recently reported the discovery of an active site
      lysine residue that contributes to the catalytic efficiency of all nucleic acid
      polymerases (Castro, C., Smidansky, E. D., Arnold, J. J., Maksimchuk, K. R.,
      Moustafa, I., Uchida, A., Gotte, M., Konigsberg, W., and Cameron, C. E. (2009)
      Nat. Struct. Mol. Biol. 16, 212-218). Here we use a model RNA virus and its
      polymerase to show that mutation of this residue from lysine to arginine produces
      an attenuated virus that is genetically stable and elicits a protective immune
      response. Given the conservation of this residue in all viral polymerases, this
      study suggests that a universal, mechanism-based strategy may exist for viral
      attenuation and vaccine development.

PMID- 22854963
TI  - The antisense RNA As1_flv4 in the Cyanobacterium Synechocystis sp. PCC 6803
      prevents premature expression of the flv4-2 operon upon shift in inorganic carbon
      supply.
AB  - The functional relevance of natural cis-antisense transcripts is mostly unknown.
      Here we have characterized the association of three antisense RNAs and one
      intergenically encoded noncoding RNA with an operon that plays a crucial role in
      photoprotection of photosystem II under low carbon conditions in the
      cyanobacterium Synechocystis sp. PCC 6803. Cyanobacteria show strong gene
      expression dynamics in response to a shift of cells from high carbon to low
      levels of inorganic carbon (C(i)), but the regulatory mechanisms are poorly
      understood. Among the most up-regulated genes in Synechocystis are flv4, sll0218,
      and flv2, which are organized in the flv4-2 operon. The flavodiiron proteins
      encoded by this operon open up an alternative electron transfer route, likely
      starting from the Q(B) site in photosystem II, under photooxidative stress
      conditions. Our expression analysis of cells shifted from high carbon to low
      carbon demonstrated an inversely correlated transcript accumulation of the flv4-2
      operon mRNA and one antisense RNA to flv4, designated as As1_flv4. Overexpression
      of As1_flv4 led to a decrease in flv4-2 mRNA. The promoter activity of as1_flv4
      was transiently stimulated by C(i) limitation and negatively regulated by the
      AbrB-like transcription regulator Sll0822, whereas the flv4-2 operon was
      positively regulated by the transcription factor NdhR. The results indicate that
      the tightly regulated antisense RNA As1_flv4 establishes a transient threshold
      for flv4-2 expression in the early phase after a change in C(i) conditions. Thus,
      it prevents unfavorable synthesis of the proteins from the flv4-2 operon.

PMID- 22854964
TI  - Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/beta
      catenin pathway in human cancer.
AB  - Telomerase activation plays a critical role in human carcinogenesis through the
      maintenance of telomeres, but the activation mechanism during carcinogenesis
      remains unclear. The human telomerase reverse transcriptase (hTERT) promoter has
      been shown to promote hTERT gene expression selectively in tumor cells but not in
      normal cells. Deregulation of the Wnt/beta-catenin signaling pathway is reported
      to be associated with human carcinogenesis. However, little is known about
      whether the Wnt/beta-catenin pathway is involved in activating hTERT
      transcription and inducing telomerase activity (TA). In this study, we report
      that hTERT is a novel target of the Wnt/beta-catenin pathway. Transient
      activation of the Wnt/beta-catenin pathway either by transfection of a
      constitutively active form of beta-catenin or by LiCl or Wnt-3a conditioned
      medium treatment induced hTERT mRNA expression and elevated TA in different cell
      lines. Furthermore, we found that silencing endogenous beta-catenin expression by
      beta-catenin gene-specific shRNA effectively decreased hTERT expression,
      suppressed TA, and accelerated telomere shortening. Of the four members of the
      lymphoid-enhancing factor (LEF)/T-cell factor (TCF) family, only TCF4 showed more
      effective stimulation on the hTERT promoter. Ectopic expression of a dominant
      negative form of TCF4 inhibited hTERT expression in cancer cells. Through
      promoter mapping, electrophoretic mobility shift assay, and chromatin
      immunoprecipitation assay, we found that hTERT is a direct target of beta
      catenin.TCF4-mediated transcription and that the TCF4 binding site at the hTERT
      promoter is critical for beta-catenin.TCF4-dependent expression regulation. Given
      the pivotal role of telomerase in carcinogenesis, these results may offer insight
      into the regulation of telomerase in human cancer.

PMID- 22854965
TI  - NF-kappaB-dependent microRNA-125b up-regulation promotes cell survival by
      targeting p38alpha upon ultraviolet radiation.
AB  - UV-induced stress response involves expression change of a myriad of genes, which
      play critical roles in modulating cell cycle arrest, DNA repair, and cell
      survival. Alteration of microRNAs has been found in cells exposed to UV, yet
      their function in UV stress response remains elusive. Here, we show that UV
      radiation induces up-regulation of miR-125b, which negatively regulates p38alpha
      expression through targeting its 3'-UTR. Increase of miR-125b depends on UV
      induced NF-kappaB activation, which enhances miR-125b gene transcription upon UV
      radiation. The DNA damage-responsive kinase ATM (ataxia telangiectasia mutated)
      is indispensable for UV-induced NF-kappaB activation, which may regulate p38alpha
      activation and IKKbeta-dependent IkappaBalpha degradation in response to UV.
      Consequently, repression of p38alpha by miR-125b prohibits prolonged
      hyperactivation of p38alpha by UV radiation, which is required for protecting
      cells from UV-induced apoptosis. Altogether, our data support a critical role of
      NF-kappaB-dependent up-regulation of miR-125b, which forms a negative feedback
      loop to repress p38alpha activation and promote cell survival upon UV radiation.

PMID- 22854966
TI  - DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma
      cells as subunits of Elongator.
AB  - The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII
      transcript elongation through histone acetylation in the nucleus as well as tRNA
      modification in the cytoplasm. This acetyltransferase complex directly or
      indirectly regulates numerous biological processes ranging from exocytosis and
      resistance to heat shock in yeast to cell migration and neuronal differentiation
      in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported
      but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6
      (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further
      investigated the importance and function of these two subunits by a combination
      of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is
      required for the integrity of Elongator and directly connects ELP3 to ELP4.
      Importantly, the migration and tumorigenicity of melanoma-derived cells are
      significantly decreased upon Elongator depletion through ELP1 or ELP3.
      Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar
      defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are
      essential for Elongator function. Together, our data identify DERP6/ELP5 and
      C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of
      melanoma cells, as integral subunits of Elongator.

PMID- 22854967
TI  - Opposite stereoselectivities of dirigent proteins in Arabidopsis and schizandra
      species.
AB  - How stereoselective monolignol-derived phenoxy radical-radical coupling reactions
      are differentially biochemically orchestrated in planta, whereby for example they
      afford (+)- and (-)-pinoresinols, respectively, is both a fascinating mechanistic
      and evolutionary question. In earlier work, biochemical control of (+)
      pinoresinol formation had been established to be engendered by a (+)-pinoresinol
      forming dirigent protein in Forsythia intermedia, whereas the presence of a (-)
      pinoresinol-forming dirigent protein was indirectly deduced based on the
      enantiospecificity of downstream pinoresinol reductases (AtPrRs) in Arabidopsis
      thaliana root tissue. In this study of 16 putative dirigent protein homologs in
      Arabidopsis, AtDIR6, AtDIR10, and AtDIR13 were established to be root-specific
      using a beta-glucuronidase reporter gene strategy. Of these three, in vitro
      analyses established that only recombinant AtDIR6 was a (-)-pinoresinol-forming
      dirigent protein, whose physiological role was further confirmed using
      overexpression and RNAi strategies in vivo. Interestingly, its closest homolog,
      AtDIR5, was also established to be a (-)-pinoresinol-forming dirigent protein
      based on in vitro biochemical analyses. Both of these were compared in terms of
      properties with a (+)-pinoresinol-forming dirigent protein from Schizandra
      chinensis. In this context, sequence analyses, site-directed mutagenesis, and
      region swapping resulted in identification of putative substrate binding
      sites/regions and candidate residues controlling distinct stereoselectivities of
      coupling modes.

PMID- 22854968
TI  - The deactive form of respiratory complex I from mammalian mitochondria is a
      Na+/H+ antiporter.
AB  - In mitochondria, complex I (NADH:ubiquinone oxidoreductase) uses the redox
      potential energy from NADH oxidation by ubiquinone to transport protons across
      the inner membrane, contributing to the proton-motive force. However, in some
      prokaryotes, complex I may transport sodium ions instead, and three subunits in
      the membrane domain of complex I are closely related to subunits from the Mrp
      family of Na(+)/H(+) antiporters. Here, we define the relationship between
      complex I from Bos taurus heart mitochondria, a close model for the human enzyme,
      and sodium ion transport across the mitochondrial inner membrane. In accord with
      current consensus, we exclude the possibility of redox-coupled Na(+) transport by
      B. taurus complex I. Instead, we show that the "deactive" form of complex I,
      which is formed spontaneously when enzyme turnover is precluded by lack of
      substrates, is a Na(+)/H(+) antiporter. The antiporter activity is abolished upon
      reactivation by the addition of substrates and by the complex I inhibitor
      rotenone. It is specific for Na(+) over K(+), and it is not exhibited by complex
      I from the yeast Yarrowia lipolytica, which thus has a less extensive deactive
      transition. We propose that the functional connection between the redox and
      transporter modules of complex I is broken in the deactive state, allowing the
      transport module to assert its independent properties. The deactive state of
      complex I is formed during hypoxia, when respiratory chain turnover is slowed,
      and may contribute to determining the outcome of ischemia-reperfusion injury.

PMID- 22854969
TI  - Distinctive features of catalytic and transport mechanisms in mammalian sarco
      endoplasmic reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases.
AB  - Ca(2+) (sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA)) and Cu(+) (ATP7A/B)
      ATPases utilize ATP through formation of a phosphoenzyme intermediate (E-P)
      whereby phosphorylation potential affects affinity and orientation of bound
      cation. SERCA E-P formation is rate-limited by enzyme activation by Ca(2+),
      demonstrated by the addition of ATP and Ca(2+) to SERCA deprived of Ca(2+) (E2)
      as compared with ATP to Ca(2+)-activated enzyme (E1.2Ca(2+)). Activation by
      Ca(2+) is slower at low pH (2H(+).E2 to E1.2Ca(2+)) and little sensitive to
      temperature-dependent activation energy. On the other hand, subsequent (forward
      or reverse) phosphoenzyme processing is sensitive to activation energy, which
      relieves conformational constraints limiting Ca(2+) translocation. A "H(+)-gated
      pathway," demonstrated by experiments on pH variations, charge transfer, and Glu
      309 mutation allows luminal Ca(2+) release by H(+)/Ca(2+) exchange. As compared
      with SERCA, initial utilization of ATP by ATP7A/B is much slower and highly
      sensitive to temperature-dependent activation energy, suggesting conformational
      constraints of the headpiece domains. Contrary to SERCA, ATP7B phosphoenzyme
      cleavage shows much lower temperature dependence than EP formation. ATP-dependent
      charge transfer in ATP7A and -B is observed, with no variation of net charge upon
      pH changes and no evidence of Cu(+)/H(+) exchange. As opposed to SERCA after
      Ca(2+) chelation, ATP7A/B does not undergo reverse phosphorylation with P(i)
      after copper chelation unless a large N-metal binding extension segment is
      deleted. This is attributed to the inactivating interaction of the copper
      deprived N-metal binding extension with the headpiece domains. We conclude that
      in addition to common (P-type) phosphoenzyme intermediate formation, SERCA and
      ATP7A/B possess distinctive features of catalytic and transport mechanisms.

PMID- 22854970
TI  - Crystal structure and functional characterization of the complement regulator
      mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1).
AB  - The human lectin complement pathway activation molecules comprise mannose-binding
      lectin (MBL) and ficolin-1, -2, and -3 in complex with associated serine
      proteases MASP-1, -2, and -3 and the non-enzymatic small MBL associated protein
      or sMAP. Recently, a novel plasma protein named MBL/ficolin-associated protein-1
      (MAP-1) was identified in humans. This protein is the result of a differential
      splicing of the MASP1 gene and includes the major part of the heavy chain but
      lacks the serine protease domain. We investigated the direct interactions of MAP
      1 and MASP-3 with ficolin-3 and MBL using surface plasmon resonance and found
      affinities around 5 nm and 2.5 nm, respectively. We studied structural aspects of
      MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a
      calcium-dependent homodimer in solution. We were able to determine the crystal
      structure of MAP-1, which also contains a head-to-tail dimer ~146 A long. This
      structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in
      its entirety. Finally we found that MAP-1 competes with all three MASPs for
      ligand binding and is able to mediate a strong dose-dependent inhibitory effect
      on the lectin pathway activation, as measured by levels of C3 and C9.

PMID- 22854972
TI  - Sigma level performance of the innovated process in the imaging department at a
      Mexican health institute.
AB  - The National Institute of Respiratory Diseases is a third level public hospital
      in Mexico City, which in 2007 acquired an RIS-PACS to be implemented at its
      Imaging Department (ID), with the objective to enhance its service. This
      department attends an average of 3,500 patients per month developing different
      image modalities. The objective of this work was to determine the overall sigma
      level performance of four processes of the ID: reception, X-ray, computed
      tomography, and radiologist diagnosis, considering process analysis and
      innovation through Six Sigma methodology, measuring the innovation effectiveness
      by means of indicators and learning curves. Initially, a first measurement (M 1)
      of the original processes was determined; once 13 innovations were implemented in
      a pilot program, two more measurements were done, 15 days after (M 2) and 30 days
      after (M 3), in order to know the impact of the innovations in the ID processes.
      The initial sigma level of the ID before innovations was sigma 1 = 2.0, which
      means that there were 36 patients per day with a process defect during their stay
      at the ID. In the two following measurements, sigma 2 = 2.2 which means that
      there were 28 patients per day with a process defect, and sigma 3 = 2.3 with 24
      patients per day with a process defect. These results demonstrate that the
      percentage of performance enhancement between the original process and 15 days
      later was 23 % and 30 days later an enhancement of 15 %. In total, an overall
      enhancement of 38 % was obtained at the ID of the institute.

PMID- 22854973
TI  - Region-based nasopharyngeal carcinoma lesion segmentation from MRI using
      clustering- and classification-based methods with learning.
AB  - In clinical diagnosis of nasopharyngeal carcinoma (NPC) lesion, clinicians are
      often required to delineate boundaries of NPC on a number of tumor-bearing
      magnetic resonance images, which is a tedious and time-consuming procedure highly
      depending on expertise and experience of clinicians. Computer-aided tumor
      segmentation methods (either contour-based or region-based) are necessary to
      alleviate clinicians' workload. For contour-based methods, a minimal user
      interaction to draw an initial contour inside or outside the tumor lesion for
      further curve evolution to match the tumor boundary is preferred, but parameters
      within most of these methods require manual adjustment, which is technically
      burdensome for clinicians without specific knowledge. Therefore, segmentation
      methods with a minimal user interaction as well as automatic parameters
      adjustment are often favored in clinical practice. In this paper, two region
      based methods with parameters learning are introduced for NPC segmentation. Two
      hundred fifty-three MRI slices containing NPC lesion are utilized for evaluating
      the performance of the two methods, as well as being compared with other similar
      region-based tumor segmentation methods. Experimental results demonstrate the
      superiority of adopting learning in the two introduced methods. Also, they
      achieve comparable segmentation performance from a statistical point of view.

PMID- 22854971
TI  - Phosphatidylethanolamine binding is a conserved feature of cyclotide-membrane
      interactions.
AB  - Cyclotides are bioactive cyclic peptides isolated from plants that are
      characterized by a topologically complex structure and exceptional resistance to
      enzymatic or thermal degradation. With their sequence diversity, ultra-stable
      core structural motif, and range of bioactivities, cyclotides are regarded as a
      combinatorial peptide template with potential applications in drug design. The
      mode of action of cyclotides remains elusive, but all reported biological
      activities are consistent with a mechanism involving membrane interactions. In
      this study, a diverse set of cyclotides from the two major subfamilies, Mobius
      and bracelet, and an all-d mirror image form, were examined to determine their
      mode of action. Their lipid selectivity and membrane affinity were determined, as
      were their toxicities against a range of targets (red blood cells, bacteria, and
      HIV particles). Although they had different membrane-binding affinities, all of
      the tested cyclotides targeted membranes through binding to phospholipids
      containing phosphatidylethanolamine headgroups. Furthermore, the biological
      potency of the tested cyclotides broadly correlated with their ability to target
      and disrupt cell membranes. The finding that a broad range of cyclotides target a
      specific lipid suggests their categorization as a new lipid-binding protein
      family. Knowledge of their membrane specificity has the potential to assist in
      the design of novel drugs based on the cyclotide framework, perhaps allowing the
      targeting of peptide drugs to specific cell types.

PMID- 22854974
TI  - Vibrational circular dichroism spectroscopy of two chiral binaphthyl diphosphine
      ligands and their palladium complexes in solution.
AB  - BINAP (2,2'-diphenylphosphino-1,1'-binaphthyl) is a unique binaphthyl diphosphine
      ligand with axial chirality. The palladium complexes of BINAP and of its
      derivative TOLBINAP have found extensive applications in the field of asymmetric
      syntheses. The conformational changes in the BINAP and TOLBINAP ligands before
      and after coordination with palladium have been investigated using density
      functional theory, vibrational absorbance (VA) and vibrational circular dichroism
      (VCD) spectroscopy. VA and VCD spectra of these two chiral ligands and their
      corresponding palladium complexes have been recorded in CDCl(3) solution.
      Extensive conformational searches have been carried out for both the ligands and
      the associated palladium complexes. Coordination with palladium has been found to
      introduce structural rigidity to the ligands. The calculated VA and VCD spectra
      of the ligands and complexes in the gas phase show substantial differences to the
      experimental data. Incorporation of the implicit polarisable continuum solvation
      model has provided much better agreement between theory and experiment,
      especially for the complexes, allowing clear identification of the species and
      conformations. This and the high specificity of VCD spectral signatures to
      chirality and to conformations suggest the potential applications of VCD
      spectroscopy for following these important catalytic species in solution
      reactions directly.

PMID- 22854975
TI  - Electronic structure and quantum transport properties of trilayers formed from
      graphene and boron nitride.
AB  - We report the results of a theoretical study of graphene/BN/graphene and
      BN/graphene/BN trilayers using the van-der-Waals-corrected density functional
      theory in conjunction with the non-equilibrium Green's Function method. These
      trilayer systems formed from graphene and BN exhibit distinct stacking-dependent
      features in their ground state electronic structure and response to an applied
      electric field perpendicular to the trilayer planes. The graphene/BN/graphene
      system shows a negligible gap in the electronic band structure that increases for
      the AAA and ABA stackings under an external electric field, while the zero-field
      band gap of BN/graphene/BN remains unaffected by the electric field. When both
      types of trilayer systems are contacted with gold electrodes, a metal-like
      conduction is predicted in the low-field regime, which changes to a p-type
      conduction with an increase in the applied perpendicular bias field.

PMID- 22854976
TI  - Regularized logistic regression and multiobjective variable selection for
      classifying MEG data.
AB  - This paper addresses the question of maximizing classifier accuracy for
      classifying task-related mental activity from Magnetoencelophalography (MEG)
      data. We propose the use of different sources of information and introduce an
      automatic channel selection procedure. To determine an informative set of
      channels, our approach combines a variety of machine learning algorithms: feature
      subset selection methods, classifiers based on regularized logistic regression,
      information fusion, and multiobjective optimization based on probabilistic
      modeling of the search space. The experimental results show that our proposal is
      able to improve classification accuracy compared to approaches whose classifiers
      use only one type of MEG information or for which the set of channels is fixed a
      priori.

PMID- 22854977
TI  - Human pitch detectors are tuned on a fine scale, but are perceptually accessed on
      a coarse scale.
AB  - Single neurons in auditory cortex display highly selective spectrotemporal
      properties: their receptive fields modulate over small fractions of an octave and
      integrate across temporal windows of 100-200 ms. We investigated how these
      characteristics impact auditory behavior. Human observers were asked to detect a
      specific sound frequency masked by broadband noise; we adopted an experimental
      design which required the engagement of frequency-selective mechanisms to perform
      above chance. We then applied psychophysical reverse correlation to derive
      spectrotemporal perceptual filters for the assigned task. We were able to expose
      signatures of neuronal-like spectrotemporal tuning on a scale of 1/10 octave and
      50-100 ms, but detailed modeling of our results showed that observers were not
      able to rely on the explicit output of these channels. Instead, human observers
      pooled from a large bank of highly selective channels via a weighting envelope
      poorly tuned for frequency (on a scale of 1.5 octave) with sluggish temporal
      dynamics, followed by a highly nonlinear max-like operation. We conclude that
      human detection of specific frequencies embedded within complex sounds suffers
      from a high degree of intrinsic spectrotemporal uncertainty, resulting in low
      efficiency values (<1 %) for this perceptual ability. Signatures of the
      underlying neural circuitry can be exposed, but there does not appear to be a
      direct line for accessing individual neural channels on a fine scale.

PMID- 22854978
TI  - Regulation of advance directives in Italy: a bad law in the making.
AB  - PURPOSE: The Advance Directives (ADs) have been adopted in many countries to
      defend patients' autonomy. In Italy, the role of ADs has recently been the
      subject of heated debate involving political parties and the Roman Catholic
      Church. In February 2009, the conservative government coalition presented a bill
      of law on this issue. It has been passed by the Low Chamber and is now being
      discussed in the Senate.  The purpose of the article is to highlight any possible
      bill's contradiction with Italian Constitution, Italian Code of Medical Ethics
      (ICME), and Oviedo Convention contents, relevant for intensivists. METHODS:
      Analysis of bill's content in the light of Italian Constitution, ICME, Oviedo
      Convention articles and in comparison with French legislation regarding end of
      life (Leonetti law). RESULTS: In the Authors' point of view the bill's articles 
      limit the moral and judicial importance of four main issues as informed consent,
      permanent incapacity, artificial nutrition/hydration, and withdraw/withhold
      treatments. CONCLUSIONS: In the Authors' opinion the ADs must represent informed
      preferences made freely by patients within the relationship with their
      physicians, as part of an advance care planning. When this relationship develops
      in accordance with the ICME rules, it contains all of the ethical/professional
      dimensions to legitimate right choices in each case. The law should draw
      inspiration from ICME principles, assigning them a juridical power, acknowledging
      their validity in legitimating end-of-life decisions, and defining a framework of
      juridical legitimacy for these decisions without infringing on patients' right to
      autonomy with prescriptions on the care.

PMID- 22854979
TI  - Elderly age as a prognostic marker of 1-year poor outcome for subarachnoid
      hemorrhage patients through its interaction with admission hydrocephalus.
AB  - BACKGROUND: An increasing number of elderly patients are treated for aneurysmal
      subarachnoid hemorrhage. Given that elderly age is associated with both poor
      outcome and an increased risk of hydrocephalus, we sought to investigate the
      interaction between age and hydrocephalus in outcome prediction. METHODS: We
      enrolled 933 consecutive patients treated for subarachnoid hemorrhage between
      2002 and 2010 and followed them for 1 yr after intensive care unit discharge. We
      first performed stepwise analyses to determine the relationship among neurologic
      events, elderly age (60 or more yr old), and 1-yr poor outcome (defined as Rankin
      4-6). Within the most parsimonious model, we then tested for interaction between
      admission hydrocephalus and elderly age. Finally, we tested the association
      between age as a stratified variable and 1-yr poor outcome for each subgroup of
      patients with neurologic events. RESULTS: 24.1% (n=225) of subarachnoid
      hemorrhage patients were 60 yr old or more and 19.3% (n=180) had 1-yr poor
      outcomes. In the most parsimonious model (area under the receiver operating
      characteristic curve, 0.84; 95% CI: 0.82 to 0.88; P<0.001), elderly age and
      admission hydrocephalus were two independent predictors for 1-yr outcome (P<0.001
      and P=0.004, respectively). Including the significant interaction between age and
      hydrocephalus (P=0.04) improved the model's outcome prediction (P=0.03), but
      elderly age was no longer a significant predictor. Finally, stratified age was
      associated with 1-yr poor outcome for hydrocephalus patients (P=0.007), but not
      for patients without hydrocephalus (P=0.87). CONCLUSION: In this observational
      study, elderly age and admission hydrocephalus predicted poor outcome, but
      elderly age without hydrocephalus did not. An external validation, however, will
      be needed to generalize this finding.

PMID- 22854981
TI  - Acquired liver injury in the intensive care unit.

PMID- 22854980
TI  - Roles of aldosterone and oxytocin in abnormalities caused by sevoflurane
      anesthesia in neonatal rats.
AB  - BACKGROUND: The authors sought to determine whether subjects with
      pathophysiological conditions that are characterized by increased concentrations
      of aldosterone have increased susceptibility to the side effects of neonatal
      anesthesia with sevoflurane. METHODS: Postnatal day 4-20 (P4-P20) rats were
      exposed to sevoflurane, 6% and 2.1%, for 3 min and 60-360 min, respectively.
      Exogenous aldosterone was administered to imitate pathophysiological conditions
      with increased concentrations of aldosterone. RESULTS: Six hours of anesthesia
      with sevoflurane on P4-P5 rats resulted in a more than 30-fold increase in serum
      concentrations of aldosterone (7.02 +/- 1.61 ng/dl vs. 263.75 +/- 22.31 ng/dl,
      mean +/- SE, n = 5-6) and reduced prepulse inhibition of the acoustic startle
      response (F(2,37) = 5.66, P < 0.001). Administration of exogenous aldosterone
      during anesthesia with sevoflurane enhanced seizure-like electroencephalogram
      patterns in neonatal rats (48.25 +/- 15.91 s vs. 222.00 +/- 53.87 s, mean +/- SE,
      n = 4) but did not affect electroencephalographic activity in older rats.
      Exogenous aldosterone increased activation of caspase-3 (F(3,28) = 11.02, P <
      0.001) and disruption of prepulse inhibition of startle (F(3,46) = 6.36; P =
      0.001) caused by sevoflurane. Intracerebral administration of oxytocin receptor
      agonists resulted in depressed seizure-like electroencephalogram patterns
      (F(2,17) = 6.37, P = 0.009), reduced activation of caspase-3 (t(11) = 2.83, P =
      0.016), and disruption of prepulse inhibition of startle (t(7) = -2.9; P = 0.023)
      caused by sevoflurane. CONCLUSIONS: These results suggest that adverse
      developmental effects of neonatal anesthesia with sevoflurane may involve both
      central and peripheral actions of the anesthetic. Subjects with increased
      concentrations of aldosterone may be more vulnerable, whereas intracerebral
      oxytocin receptor agonists may be neuroprotective.

PMID- 22854982
TI  - Symptom burden of adults with type 2 diabetes across the disease course: diabetes
      & aging study.
AB  - BACKGROUND: Reducing symptom burden is paramount at the end-of-life, but
      typically considered secondary to risk factor control in chronic disease, such as
      diabetes. Little is known about the symptom burden experienced by adults with
      type 2 diabetes and the need for symptom palliation. OBJECTIVE: To examine pain
      and non-pain symptoms of adults with type 2 diabetes over the disease course - at
      varying time points before death and by age. DESIGN: Survey follow-up study.
      PARTICIPANTS: 13,171 adults with type 2 diabetes, aged 30-75 years, from Kaiser
      Permanente, Northern California, who answered a baseline symptom survey in 2005
      2006. MAIN MEASURES: Pain and non-pain symptoms were identified by self-report
      and medical record data. Survival status from baseline was categorized into <= 6,
      >6-24, or alive >24 months. KEY RESULTS: Mean age was 60 years; 48 % were women,
      and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported
      chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 %
      insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent
      in all survival status categories, but was more prevalent among those with
      shorter survival, p< .001. Adults >= 60 years who were alive >24 months reported
      more physical symptoms such as acute pain and dyspnea, whereas participants <60
      years reported more psychosocial symptoms, such as depressed mood and insomnia.
      Adjustment for duration of diabetes and comorbidity reduced the association
      between age and pain, but did not otherwise change our results. CONCLUSIONS: In a
      diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were
      common among all patients, not only among those near the end of life. However,
      symptoms were more prevalent among patients with shorter survival. Older adults
      reported more physical symptoms, whereas younger adults reported more
      psychosocial symptoms. Diabetes care management should include not only good
      cardiometabolic control, but also symptom palliation across the disease course.

PMID- 22854984
TI  - Prognostic value of pretreatment 18F-FDG PET/CT and human papillomavirus type 16
      testing in locally advanced oropharyngeal squamous cell carcinoma.
AB  - PURPOSE: Human papillomavirus type 16 (HPV-16) positivity is associated with
      favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report
      here a study of the prognostic significance of (18)F-FDG PET/CT functional
      parameters and HPV-16 infection in OPSCC patients. METHODS: We retrospectively
      analysed 60 patients with stage III or IV OPSCC who had had a pretherapy (18)F
      FDG PET/CT scan and had completed concurrent chemoradiotherapy (n = 58) or
      curative radiotherapy (n = 2). All patients were followed up for >=24 months or
      until death. We determined total lesion glycolysis (TLG) and the maximal
      standardized uptake values (SUV(max)) of the primary tumour and neck lymph nodes
      from the pretherapy (18)F-FDG PET/CT scan. Optimal cut-offs of the (18)F-FDG
      PET/CT parameters were obtained by receiver operating characteristic (ROC) curve
      analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to
      determine HPV infection status. RESULTS: The pretherapy tumour biopsies were
      positive for HPV-16 in 12 patients (20.0 %). Cox regression analyses revealed HPV
      16 positivity and tumour TLG >135.3 g to be independently associated with overall
      survival (p = 0.027 and 0.011, respectively). However, only tumour TLG >135.3 g
      was independently associated with progression-free survival, disease-free
      survival and locoregional control (p = 0.011, 0.001 and 0.034, respectively). A
      scoring system was formulated to define distinct overall survival groups using
      tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG
      <=135.3 g experienced better survival than those with tumour TLG >135.3 g and no
      HPV infection (p = 0.001). CONCLUSION: Tumour TLG was an independent predictor of
      survival in patients with locally advanced OPSCC. A scoring system was developed
      and may serve as a risk stratification strategy for guiding therapy.

PMID- 22854985
TI  - Clinical significance of MRI/(18)F-FDG PET fusion imaging of the spinal cord in
      patients with cervical compressive myelopathy.
AB  - PURPOSE: (18)F-FDG PET is used to investigate the metabolic activity of neural
      tissue. MRI is used to visualize morphological changes, but the relationship
      between intramedullary signal changes and clinical outcome remains controversial.
      The present study was designed to evaluate the use of 3-D MRI/(18)F-FDG PET
      fusion imaging for defining intramedullary signal changes on MRI scans and local
      glucose metabolic rate measured on (18)F-FDG PET scans in relation to clinical
      outcome and prognosis. METHODS: We studied 24 patients undergoing decompressive
      surgery for cervical compressive myelopathy. All patients underwent 3-D MRI and
      (18)F-FDG PET before surgery. Quantitative analysis of intramedullary signal
      changes on MRI scans included calculation of the signal intensity ratio (SIR) as
      the ratio between the increased lesional signal intensity and the signal
      intensity at the level of the C7/T1 disc. Using an Advantage workstation, the
      same slices of cervical 3-D MRI and (18)F-FDG PET images were fused. On the fused
      images, the maximal count of the lesion was adopted as the standardized uptake
      value (SUV(max)). In a similar manner to SIR, the SUV ratio (SUVR) was also
      calculated. Neurological assessment was conducted using the Japanese Orthopedic
      Association (JOA) scoring system for cervical myelopathy. RESULTS: The SIR on T1
      weighted (T1-W) images, but not SIR on T2-W images, was significantly correlated
      with preoperative JOA score and postoperative neurological improvement. Lesion
      SUV(max) was significantly correlated with SIR on T1-W images, but not with SIR
      on T2-W images, and also with postoperative neurological outcome. The SUVR
      correlated better than SIR on T1-W images and lesion SUV(max) with neurological
      improvement. Longer symptom duration was correlated negatively with SIR on T1-W
      images, positively with SIR on T2-W images, and negatively with SUV(max).
      CONCLUSION: Our results suggest that low-intensity signal on T1-W images, but not
      on T2-W images, is correlated with a poor postoperative neurological outcome.
      SUV(max) of lesions showing increased signal intensity and SUVR measured on
      fusion MRI/PET scans are more sensitive parameters for predicting clinical
      outcome than signal intensity on the MRI scan.

PMID- 22854986
TI  - Induction and repair of DNA double-strand breaks in blood lymphocytes of patients
      undergoing 18F-FDG PET/CT examinations.
AB  - PURPOSE: The purpose of this study was to evaluate DNA double-strand breaks
      (DSBs) in blood lymphocytes of patients undergoing positron emission tomography
      (PET)/CT using gamma-H2AX immunofluorescence microscopy and to differentiate
      between (18)F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions. METHODS: This
      study was approved by the local Ethics Committee and complies with Health
      Insurance Portability and Accountability Act (HIPAA) requirements. After written
      informed consent was obtained, 33 patients underwent whole-body (18)F-FDG PET/CT
      (3 MBq/kg body weight, 170/100 reference mAs at 120 kV). The FDG PET and CT
      portions were performed as an initial CT immediately followed by the PET. Blood
      samples were obtained before, at various time points following (18)F-FDG
      application and up to 24 h after the CT scan. Distinct foci representing DSBs
      were quantified in isolated lymphocytes using fluorescence microscopy after
      staining against the phosphorylated histone variant gamma-H2AX. RESULTS: The DSB
      values at the various time points were significantly different (p < 0.001). The
      median baseline level was 0.08/cell (range 0.06-0.12/cell). Peaks of radiation
      induced DSBs were found 30 min after (18)F-FDG administration (median excess foci
      0.11/cell, range 0.06-0.27/cell) and 5 min after CT (median excess foci
      0.17/cell, range 0.05-0.54/cell). A significant correlation between CT-induced
      DSBs and dose length product was obtained (rho = 0.898, p < 0.001). After 24 h
      DSB values were still slightly but significantly elevated (median foci 0.11/cell,
      range 0.10-0.14/cell, p = 0.003) compared to pre-exposure levels. CONCLUSION:
      PET/CT-induced DSBs can be monitored using gamma-H2AX immunofluorescence
      microscopy. Peak values may be obtained 30 min after (18)F-FDG injection and 5
      min after CT. The radionuclide contributes considerably to the total DSB
      induction in this setting.

PMID- 22854987
TI  - Asymmetric functionalization of colloidal dimer particles with gold
      nanoparticles.
AB  - We present a method to asymmetrically functionalize dimer particles with gold
      nanoparticles. Our method enables the fabrication of asymmetrically
      functionalized dimer particles on a large scale.

PMID- 22854988
TI  - Use of platelet-leukocyte membrane in arthroscopic repair of large rotator cuff
      tears: a prospective randomized study.
AB  - BACKGROUND: Arthroscopic rotator cuff repair generally provides satisfactory
      results including decreased shoulder pain and improved shoulder motion.
      Unfortunately, imaging studies demonstrate that the retear rate associated with
      the available arthroscopic techniques may be high. The purpose of this study was
      to evaluate the clinical and magnetic resonance imaging (MRI) results of
      arthroscopic rotator cuff repair with and without the use of platelet-leukocyte
      membrane in patients with a large posterosuperior rotator cuff tear. METHODS:
      Eighty consecutive patients with a large full-thickness posterosuperior rotator
      cuff tear were enrolled. All tears were repaired using an arthroscopic single-row
      technique. Patients were randomized to treatment either with or without a
      platelet-leukocyte membrane inserted between the rotator cuff tendon and its
      footprint. In patients treated with this membrane, one membrane was utilized for
      each suture anchor. The primary outcomes were the difference between the
      preoperative and postoperative Constant scores and the repair integrity assessed
      by MRI according to the Sugaya classification. The secondary outcome was the
      difference between the preoperative and postoperative Simple Shoulder Test (SST)
      scores. RESULTS: The only significant differences between the two groups involved
      the patient age and the preoperative and postoperative Constant scores; the
      differences in the Constant score were due to differences in the shoulder pain
      subscore. At a mean of thirteen months of follow-up, rotator cuff retears were
      observed only in the group of patients in whom the membrane had not been used,
      and a thin but intact tendon was observed more frequently in this group as well.
      The use of the membrane was associated with significantly better repair integrity
      (p = 0.04). CONCLUSIONS: The use of the platelet-leukocyte membrane in the
      treatment of rotator cuff tears improved repair integrity compared with repair
      without membrane. However, the improvement in repair integrity was not associated
      with greater improvement in the functional outcome. In fact, the Constant scores
      of the two groups would have been similar if the shoulder pain component (which
      had differed preoperatively) had been excluded.

PMID- 22854989
TI  - The cost-effectiveness of single-row compared with double-row arthroscopic
      rotator cuff repair.
AB  - BACKGROUND: Interest in double-row techniques for arthroscopic rotator cuff
      repair has increased over the last several years, presumably because of a
      combination of literature demonstrating superior biomechanical characteristics
      and recent improvements in instrumentation and technique. As a result of the
      increasing focus on value-based health-care delivery, orthopaedic surgeons must
      understand the cost implications of this practice. The purpose of this study was
      to examine the cost-effectiveness of double-row arthroscopic rotator cuff repair
      compared with traditional single-row repair. METHODS: A decision-analytic model
      was constructed to assess the cost-effectiveness of double-row arthroscopic
      rotator cuff repair compared with single-row repair on the basis of the cost per
      quality-adjusted life year gained. Two cohorts of patients (one with a tear of <3
      cm and the other with a tear of >=3 cm) were evaluated. Probabilities for retear
      and persistent symptoms, health utilities for the particular health states, and
      the direct costs for rotator cuff repair were derived from the orthopaedic
      literature and institutional data. RESULTS: The incremental cost-effectiveness
      ratio for double-row compared with single-row arthroscopic rotator cuff repair
      was $571,500 for rotator cuff tears of <3 cm and $460,200 for rotator cuff tears
      of >=3 cm. The rate of radiographic or symptomatic retear alone did not influence
      cost-effectiveness results. If the increase in the cost of double-row repair was
      less than $287 for small or moderate tears and less than $352 for large or
      massive tears compared with the cost of single-row repair, then double-row repair
      would represent a cost-effective surgical alternative. CONCLUSIONS: On the basis
      of currently available data, double-row rotator cuff repair is not cost-effective
      for any size rotator cuff tears. However, variability in the values for costs and
      probability of retear can have a profound effect on the results of the model and
      may create an environment in which double-row repair becomes the more cost
      effective surgical option. The identification of the threshold values in this
      study may help surgeons to determine the most cost-effective treatment.

PMID- 22854990
TI  - High-flexion total knee arthroplasty: survivorship and prevalence of osteolysis:
      results after a minimum of ten years of follow-up.
AB  - BACKGROUND: We are aware of no information about the mid-term performance of the
      high-flexion total knee arthroplasty, although early results have been reported.
      The purpose of this study was to evaluate the mid-term results of high-flexion
      and conventional knee prostheses. METHODS: We prospectively compared the results
      of 100 patients with osteoarthritis who had received a NexGen Legacy Posterior
      Stabilized (NexGen LPS) prosthesis in one knee and a NexGen Legacy Posterior
      Stabilized-Flex (NexGen LPS-Flex) prosthesis in the other. Seventy-five patients
      (150 knees) were women and twenty-five (fifty knees) were men. The mean age was
      sixty-five years (range, forty-eight to eighty-five years) at the time of the
      index procedure. The mean duration of follow-up was 10.3 years (range, ten to
      10.6 years). The patients were assessed with radiographs, with the rating system
      of the Knee Society, and with the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) score at three months, one year, and annually
      thereafter. RESULTS: Total knee scores, knee function scores, pain scores, WOMAC
      scores, knee motion, and activity scores did not differ significantly between the
      two designs of the implants, on the basis of the numbers studied, either
      preoperatively or at the time of final follow-up. One knee in the NexGen LPS-Flex
      group was revised because of recurrent infection. No knee in either group had
      aseptic loosening of the components. The Kaplan-Meier survivorship at ten years
      postoperatively, with revision defined as the end point, was 100% (95% confidence
      interval, 94 to 100) for the NexGen LPS prosthesis and 99% (95% confidence
      interval, 93 to 100) for the NexGen LPS-Flex prosthesis. CONCLUSIONS: After a
      minimum duration of follow-up of ten years, there were no significant differences
      between the two groups with regard to implant survivorship, functional outcome,
      knee motion, or prevalence of osteolysis.

PMID- 22854991
TI  - Intraoperative three-dimensional imaging in the treatment of acute unstable
      syndesmotic injuries.
AB  - BACKGROUND: Acute unstable syndesmotic ankle injuries are treated primarily by
      reduction and stabilization with a syndesmotic screw. Examination with
      fluoroscopy or standard radiographs may not provide reliable information about
      the quality of the reduction. There is evidence that intraoperative three
      dimensional imaging can demonstrate a large proportion of malreductions. The aim
      of this study was to determine whether intraoperative three-dimensional imaging
      improves the detection of inadequate positioning of the distal aspect of the
      fibula in the tibiofibular incisura after syndesmotic screw insertion compared
      with the findings on standard intraoperative fluoroscopy. METHODS: Of 2286 ankle
      fractures treated operatively from August 2001 to February 2011, 251 consecutive
      cases (11%) were identified in a retrospective chart review. All had an unstable
      syndesmosis and underwent syndesmosis stabilization on the basis of an
      intraoperative hook test. After fluoroscopy, an intraoperative three-dimensional
      scan was performed. The result of this scan was documented by the surgeon and
      analyzed retrospectively with regard to the incidence and nature of the need for
      intraoperative revisions. RESULTS: The intraoperative three-dimensional scan
      altered the surgical outcome in eighty-two ankles (32.7%). In most ankles
      (seventy-seven; 30.7%), the reduction was improved, with the most common
      improvement being the alignment of the fibula in the tibiofibular incisura in
      sixty-four patients (25.5%) followed by correction of the fracture reduction in
      thirteen patients (5.2%). The other five alterations involved implant
      corrections. The most common malpositions requiring correction after insertion of
      a positioning screw, with or without additional fixation, were anterior
      displacement and internal rotation of the distal aspect of the fibula.
      CONCLUSIONS: Following open reduction and internal fixation of an ankle fracture,
      the correct position of the syndesmosis cannot be evaluated reliably with use of
      conventional radiographs or intraoperative fluoroscopy. In view of the high
      proportion of positive findings in this study, we believe that any treatment of a
      syndesmotic injury should include intraoperative three-dimensional imaging or at
      least a postoperative computed tomography scan.

PMID- 22854992
TI  - Tendon transfer options about the shoulder in patients with brachial plexus
      injury.
AB  - BACKGROUND: The purpose of this study was to evaluate the early outcome of
      shoulder tendon transfer in patients with brachial plexus injury and to determine
      the factors associated with favorable outcomes. METHODS: Fifty-two patients with
      traumatic brachial plexus injury and a paralytic shoulder were included in the
      study. All patients were evaluated at a mean of nineteen months (range, twelve to
      twenty-eight months) postoperatively. Twelve patients had a C5-6 injury, twenty
      two had a C5-7 injury, five had a C5-8 injury, and thirteen had a C5-T1 injury.
      Transfer of the lower portion of the trapezius muscle was performed either in
      isolation or as part of multiple tendon transfers to improve shoulder function.
      Additional muscles transferred included the middle and upper portions of the
      trapezius, levator scapulae, upper portion of the serratus anterior, teres major,
      latissimus dorsi, and pectoralis major. RESULTS: All patients had a stable
      shoulder postoperatively. Shoulder external rotation improved substantially in
      all patients from no external rotation (hand-on-belly position) to a mean of 20
      degrees  (p = 0.001). Patients who underwent additional transfers had marginal
      improvement of shoulder flexion, from a mean of 10 degrees  preoperatively to 60
      degrees  postoperatively, and of shoulder abduction, from a mean of 10 degrees 
      to 50 degrees  (p = 0.01 for each). Mean pain on a visual analog scale improved
      from 6 points preoperatively to 2 points postoperatively. The mean Disabilities
      of the Arm, Shoulder and Hand (DASH) score improved from 59 to 47 points (p =
      0.001). The mean Subjective Shoulder Value improved from 5% to 40% (p = 0.001).
      Greater age, higher body mass index, and more extensive nerve injury were
      associated with a poorer DASH score in a multivariate analysis (p = 0.003).
      CONCLUSIONS: Tendon transfers about the shoulder can improve shoulder function in
      patients with brachial plexus injury resulting in a paralytic shoulder.
      Significant improvement of shoulder external rotation but only marginal
      improvements of shoulder abduction and flexion can be achieved. The outcome can
      be expected to be better in patients with less severe nerve injury.

PMID- 22854993
TI  - Effects of neoadjuvant chemotherapy on image-directed planning of surgical
      resection for distal femoral osteosarcoma.
AB  - BACKGROUND: Standard therapy for localized osteosarcoma includes neoadjuvant
      chemotherapy preceding local control surgery, followed by adjuvant chemotherapy.
      When limb-salvage procedures were being developed, preoperative chemotherapy
      allowed a delay in definitive surgery to permit fabrication of custom
      endoprosthetic reconstruction implants. One rationale for its continuation as the
      care standard has been the perception that it renders surgery easier and safer.
      Our objective was to compare surgical procedures planned on the basis of magnetic
      resonance images (MRIs) of distal femoral osteosarcomas acquired before
      neoadjuvant chemotherapy with surgical procedures planned on the basis of MRIs
      acquired after neoadjuvant chemotherapy as a measure of the surgically critical
      anatomic effects of the chemotherapy. METHODS: Twenty-four consecutive patients
      with distal femoral osteosarcoma had available digital MRIs preceding and
      following neoadjuvant chemotherapy. Thorough questionnaires were used to
      catalogue surgically critical anatomic details of MRI-directed surgical planning.
      Four faculty musculoskeletal oncologic surgeons and two musculoskeletal
      radiologists evaluated the blinded and randomly ordered MRIs. Interrater and
      intrarater reliabilities were calculated with intraclass correlation
      coefficients. The Student t test and chi-square test were used to compare pre
      chemotherapy and post-chemotherapy continuous and categorical variables on the
      questionnaire. Mixed-effect regression models were employed to compare surgical
      procedures planned on the basis of pre-chemotherapy MRIs and with those planned
      on the basis of post-chemotherapy MRIs. RESULTS: The blinded reviews generated
      strong intraclass correlation coefficients for both interrater (0.772) and mean
      intrarater (0.778) reliability. The MRI-planned resections for the majority of
      tumors changed meaningfully after chemotherapy, but in inconsistent directions.
      On the basis of mixed-effect regression modeling, it appeared that more
      amputations were planned on the basis of post-chemotherapy MRIs. No other
      parameters differed in a significant and clinically meaningful fashion. Surgeons
      demonstrated their expectation that neoadjuvant chemotherapy would improve
      resectability by planning more radical surgical procedures on the basis of scans
      that they predicted had been obtained pre-chemotherapy. CONCLUSIONS: Surgeons can
      reliably record the anatomic details of a planned resection of an osteosarcoma.
      Such methods may be useful in future multi-institutional clinical trials or
      registries. The common belief that neoadjuvant chemotherapy increases the
      resectability of extremity osteosarcomas remains anecdotally based. Rigorous
      assessment of this phenomenon in larger cohorts and at other anatomic sites as
      well as re-evaluation of other arguments for neoadjuvant chemotherapy should be
      considered.

PMID- 22854995
TI  - Risk of injury to the superior gluteal nerve when using a proximal incision for
      insertion of a piriformis-entry reamed femoral intramedullary nail: a cadaveric
      study.
AB  - BACKGROUND: This cadaveric study evaluated the risk of injury to the superior
      gluteal nerve when a proximal incision site is used for insertion of an
      antegrade, reamed femoral intramedullary nail into the piriformis fossa. Based on
      prior anatomical studies, our hypothesis is that the use of a proximal incision
      site for intramedullary nail insertion will consistently injure the superior
      gluteal nerve. METHODS: A reamed femoral intramedullary nail was inserted through
      a piriformis fossa entry site in six pairs of fresh-frozen cadaver femora. The
      specimens were randomized to two groups: reaming of the femoral canal with or
      without a protective sleeve. Damage to the superior gluteal nerve was evaluated
      by means of layered dissection of specimens. Damage to any part(s) of the
      superior gluteal nerve was recorded, and the distances between the path of the
      instrumentation and nail and the branches of the superior gluteal nerve were
      measured. RESULTS: A "spray" nerve pattern of the superior gluteal nerve was
      present in all twelve specimens. The average distance and standard deviation
      between the most superior branch of the superior gluteal nerve and the
      instrumentation and nail path was 17.75 +/- 8.58 mm. The average distance between
      the most inferior branch of the superior gluteal nerve and the instrumentation
      and nail path was 22.39 +/- 10.52 mm. There were no significant differences
      between the two groups. There were no injuries to any part of the superior
      gluteal nerve regardless of whether or not a protective sleeve was used.
      CONCLUSIONS: This anatomic study demonstrated that the superior gluteal nerve is
      not at risk for injury when a proximal incision site is used to place a reamed
      intramedullary nail into the piriformis fossa.

PMID- 22854996
TI  - Distraction osteogenesis for complex foot deformities: U-osteotomy with external
      fixation.
AB  - BACKGROUND: Certain complex foot deformities can be corrected surgically with a U
      osteotomy. This osteotomy is indicated for patients with a uniform deformity of
      the entire foot relative to the tibia, preexisting stiffness and/or fusion of the
      subtalar joint, and a pain-free ankle joint. The goal is to create a plantigrade
      foot through gradual osseous repositioning of the entire foot relative to the
      tibia by means of external fixation. If needed, foot height can be increased
      simultaneously. METHODS: Fifteen complex multiplanar foot deformities in fifteen
      patients were treated with a U-osteotomy and gradual correction by means of
      external fixation. Deformities resulted from congenital causes (seven), trauma
      (three), and developmental causes (five). The mean patient age at the time of
      surgery was twenty years (range, four to sixty-three years). The mean duration of
      external fixation was five months (range, three to eleven months). The mean
      duration of follow-up was five years (range, three to nineteen years). Clinical
      and radiographic results were assessed. RESULTS: Osseous union and a plantigrade
      foot were achieved in all fifteen patients. Seven complications related to the U
      osteotomy occurred in four patients, including deep pin-track infection in two,
      premature osseous consolidation in two, postoperative tarsal tunnel syndrome in
      two, and peroneal nerve entrapment in one. When comparing the preoperative and
      final postoperative radiographs, three significant differences were observed: the
      calcaneotibial angle changed by a mean of 18 degrees  valgus (range, 6 degrees 
      to 40 degrees  valgus) (p = 0.003), the calcaneus was translated posteriorly by a
      mean of -8 mm (range, -2 to -20 mm) (p = 0.001), and foot height increased by a
      mean of 20 mm (range, 3 to 40 mm) (p < 0.001). Fourteen patients were able to
      walk without supports or assistance; one used only one cane or crutch to walk.
      CONCLUSIONS: U-osteotomy with gradual correction by means of external fixation
      can be used to obtain a plantigrade foot in patients with complex multiplanar
      deformities of the foot relative to the tibia.

PMID- 22854994
TI  - Vancomycin-modified implant surface inhibits biofilm formation and supports bone
      healing in an infected osteotomy model in sheep: a proof-of-concept study.
AB  - BACKGROUND: Implant-associated infections contribute to patient morbidity and
      health care costs. We hypothesized that surface modification of titanium fracture
      hardware with vancomycin would support bone-healing and prevent bacterial
      colonization of the implant in a large-animal model. METHODS: A unilateral
      transverse mid-diaphyseal tibial osteotomy was performed and repaired with a
      titanium locking compression plate in nine sheep. Four control animals were
      treated with an unmodified plate and five experimental animals were treated with
      a vancomycin-modified plate. The osteotomy was inoculated with 2.5 * 106 colony
      forming units of Staphylococcus aureus. The animals were killed at three months
      postoperatively, and implants were retrieved aseptically. Microbiologic and
      histologic analyses, scanning electron and confocal microscopy, and microcomputed
      tomography were performed. RESULTS: All animals completed the study. Compared
      with the treatment cohort, control animals exhibited protracted lameness in the
      operatively treated leg. Gross findings during necropsy were consistent with an
      infected osteotomy accompanied by a florid and lytic callus. Microcomputed
      tomography and histologic analysis of the tibiae further supported the presence
      of septic osteomyelitis in the control cohort. Thick biofilms were also evident,
      and bacterial cultures were positive for Staphylococcus aureus in three of four
      control animals. In contrast, animals treated with vancomycin-treated plates
      exhibited a healed osteotomy site with homogenous remodeling, there was no
      evidence of biofilm formation on the retrieved plate, and bacterial cultures from
      only one of five animals were positive for Staphylococcus aureus. CONCLUSIONS:
      Vancomycin-derivatized plate surfaces inhibited implant colonization with
      Staphylococcus aureus and supported bone-healing in an infected large-animal
      model.

PMID- 22854997
TI  - Posttraumatic elbow stiffness.
AB  - Early posttraumatic elbow contractures may be treated with a combination of
      manipulation with the patient under anesthesia followed by bracing.Extrinsic
      contractures of the elbow may be treated with open or arthroscopic release,
      whereas intrinsic and combined contractures may require tissue release as well as
      partial or total arthroplasty.

PMID- 22854998
TI  - Variability in the definition and perceived causes of delayed unions and
      nonunions: a cross-sectional, multinational survey of orthopaedic surgeons.
AB  - BACKGROUND: Despite the large number of fracture outcome studies, there remains
      variability in the definitions of fracture-healing. It is unclear how orthopaedic
      surgeons are diagnosing and managing delayed unions and nonunions in clinical
      practice. We aimed to explore the current opinions of orthopaedic surgeons with
      regard to defining, diagnosing, and treating delayed unions and nonunions in
      extremity fractures. METHODS: We developed a survey using previous literature,
      key informants in the field of orthopaedic surgery, and a sample-to-redundancy
      strategy. Our final survey contained four sections and twenty-nine questions
      focusing on demographics and surgical experience, definitions of fracture union,
      prognostic factors for union, and the need for clinical trials. The Internet
      based survey and follow-up e-mails were continued until our a priori sample size
      of a minimum of 320 completed and eligible responses were collected. RESULTS:
      Three hundred and thirty-five surgeons completed the survey. The typical
      respondent was a North American, male orthopaedic surgeon or consultant over the
      age of thirty years who had completed trauma fellowship training, worked in an
      academic practice, supervised residents, and had more than six years of
      experience in treating orthopaedic injuries. Most surgeons endorsed a lack of
      standardization in definitions for delayed unions (73%) and nonunions (55%);
      almost all agreed that defining a delayed union and nonunion should be done on
      the basis of both radiographic and clinical criteria (88%). Most respondents
      believed that the degree of soft-tissue injury (approximately 93%), smoking
      history (approximately 82%), and vascular disease (approximately 76%) increased
      the risk of healing complications. CONCLUSIONS: Surgeons use similar prognostic
      factors to define and assess delayed unions and nonunions, but there is a lack of
      consensus in the definitions of delayed union and nonunion. The need for
      standardization and future randomized trials was strongly endorsed.

PMID- 22854999
TI  - Reconstructive surgery for overcorrected clubfoot in adults.
AB  - BACKGROUND: A known complication of the surgical treatment of clubfoot deformity
      is hindfoot valgus deformity of the ankle and/or the subtalar joint leading to
      calcaneofibular and/or anterior ankle impingement and flatfoot deformity. The
      purpose of this prospective study was to assess the radiographic outcome, pain
      relief, and functional improvement in patients with symptomatic overcorrected
      clubfoot deformity who were managed with a supramalleolar osteotomy. METHODS:
      Fourteen patients with an overcorrected clubfoot deformity and a mean age of 36.9
      +/- 14.0 years were managed with a supramalleolar osteotomy. The mean duration of
      follow-up was 50.6 months. Radiographic assessment included comparison of the
      preoperative and postoperative distal tibial joint surface angle, tibiotalar
      angle, and amount of calcaneal offset on the hindfoot alignment view. Clinical
      outcomes were quantified with use of a visual analog score for pain and the
      American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score. RESULTS: No
      perioperative complications occurred. Radiographically, all osteotomy sites
      healed within eight weeks and the orientation of the distal tibial articular
      surfaces was normalized in all cases. Clinically, calcaneofibular and anterior
      ankle impingement resolved in all patients and the mean visual analog score for
      pain decreased significantly from 4.1 +/- 1.7 to 2.2 +/- 1.5 (p < 0.05). The mean
      AOFAS hindfoot score increased significantly from 51.6 +/- 12.3 preoperatively to
      77.8 +/- 11.8 postoperatively (p < 0.05). The ankle motion increased
      significantly from 25 degrees  +/- 12 degrees  preoperatively to 29 degrees  +/-
      9 degrees  postoperatively (p < 0.05). All patients walked in normal shoes.
      CONCLUSIONS: Supramalleolar osteotomy is an effective surgical procedure for the
      treatment of ankle impingement in patients with an overcorrected congenital
      clubfoot deformity. The correction is associated with a low risk of perioperative
      complications and leads to significant reduction of pain, increased ankle motion,
      and improved clinical outcome (p < 0.05).

PMID- 22855000
TI  - A study in vivo of the effects of a static compressive load on the proximal
      tibial physis in rabbits.
AB  - BACKGROUND: The effect of compression on the physis is generally defined by the
      Hueter-Volkmann principle, in which decreased linear growth of the physis results
      from increased compression. This investigation examined whether mechanically
      induced compression of rabbit physes causes changes in gene expression, cells,
      and extracellular components that promote physeal resilience and strength (type
      II collagen and aggrecan) and cartilage hypertrophy (type-X collagen and matrix
      metalloprotease-13). METHODS: Static compressive loads (10 N or 30 N) were
      applied for two or six weeks across one hind limb proximal tibial physis of
      thirteen-week-old female New Zealand White rabbits (n = 18). The contralateral
      hind limb in all rabbits underwent sham surgery with no load to serve as an
      internal control. Harvested physes were divided into portions for histological,
      immunohistochemical, and quantitative reverse transcription-polymerase chain
      reaction analysis. Gene expression was statistically analyzed by means of
      comparisons between loaded samples and unloaded shams with use of analysis of
      variance and a Tukey post hoc test. RESULTS: Compared with unloaded shams, physes
      loaded at 10 N or 30 N for two weeks and at 10 N for six weeks showed
      histological changes in cells and matrices. Physes loaded at 30 N for six weeks
      were decreased in thickness and had structurally disorganized chondrocyte
      columns, a decreased extracellular matrix, and less intense type-II and X
      collagen immunohistochemical staining. Quantitative reverse transcription
      polymerase chain reaction analysis of loaded samples compared with unloaded shams
      yielded a significantly (p <= 0.05) decreased gene expression of aggrecan and
      type-II and X collagen and no significant (p > 0.05) changes in the matrix
      metalloprotease-13 gene expression with increasing load. CONCLUSIONS: Compressed
      rabbit physes generate biochemical changes in collagens, proteoglycan, and
      cellular and tissue matrix architecture. Changes potentially weaken overall
      physeal strength, consistent with the Hueter-Volkmann principle, and lend
      understanding of the causes of pathological conditions of the physis.

PMID- 22855001
TI  - Levels of evidence in foot and ankle surgery literature: progress from 2000 to
      2010?
AB  - BACKGROUND: The focus on evidence-based medicine has led to calls for increased
      levels of evidence in surgical journals. The purpose of the present study was to
      review the levels of evidence in articles published in the foot and ankle
      literature and to assess changes in the level of evidence over a decade. METHODS:
      All of the articles in the literature from the years 2000, 2005, and 2010 in Foot
      & Ankle International and Foot and Ankle Surgery, as well as all foot and ankle
      articles from The Journal of Bone and Joint Surgery (JBJS, American [A] and
      British [B] Volumes) were analyzed. Animal, cadaver, and basic science articles;
      editorials; surveys; special topics; letters to the editor; and correspondence
      were excluded. Articles were ranked by a five-point level-of-evidence scale,
      according to guidelines from the Centre for Evidence-Based Medicine. RESULTS: A
      total of 720 articles from forty-three different countries were analyzed. The
      kappa value for interobserver reliability showed very good agreement between the
      reviewers for types of evidence (kappa = 0.816 [p < 0.01]) and excellent
      agreement for levels of evidence (kappa = 0.869 [p < 0.01]). Between 2000 and
      2010, the percentage of high levels of evidence (Levels I and II) increased (5.2%
      to 10.3%) and low levels of evidence (Levels III, IV, and V) decreased (94.8% to
      89.7%). The most frequent type of study was therapeutic. The JBJS-A produced the
      highest proportion of high levels of evidence. CONCLUSION: There has been a trend
      toward higher levels of evidence in foot and ankle surgery literature over a
      decade, but the differences did not reach significance.

PMID- 22855002
TI  - Reshaping orthopaedic resident education in systems-based practice.
AB  - BACKGROUND: Despite advances in understanding the "systems-based practice"
      competency in resident education, this topic has remained difficult to teach,
      assess, and document. The goal of this study was to perform a needs assessment
      and an analysis of the current state of systems-based practice education in
      orthopaedic residency programs across the U.S. and within our own institution.
      METHODS: A sample of orthopaedic educators and residents from across the U.S. who
      were attending the 2010 American Orthopaedic Association (AOA) Effective
      Orthopaedic Educator Course, AOA Resident Leadership Forum, and AOA Council of
      Residency Directors meeting were surveyed to determine (1) which aspects of
      systems-based practice, if any, were being taught; (2) how systems-based practice
      is being taught; and (3) how residency programs are assessing systems-based
      practice. In addition, an in-depth case study of these issues was performed by
      means of seven semi-structured focus group sessions with diverse stakeholders who
      participated in the care of musculoskeletal patients at the authors' institution.
      A quantitative approach was used to analyze the survey data. The focus group data
      were analyzed with procedures associated with grounded theory, relying on a
      constant comparative method to develop salient themes arising from the
      discussion. RESULTS: "Clinical observation" (33%) and "didactic case-based
      learning" (23%) were reported by the survey respondents as the most commonly used
      teaching methods, but specific topics were taught inconsistently. Competency
      assessment was reported to occur infrequently, and 36% of respondents reported
      that systems-based practice areas were not being assessed by any methods. The
      focus group discussions emphasized the need for standardized experiential
      learning that was closely linked to the patient's perspective. Orthopaedic
      faculty members were uncomfortable with their knowledge of this competency and
      their ability to teach and assess it. CONCLUSIONS: Teaching the systems-based
      practice competency occurs inconsistently, and formal assessment occurs
      infrequently. In addition to formal teaching, learning systems-based practice
      will be best achieved experientially and from the patient's perspective.

PMID- 22855003
TI  - Platelet-rich plasma: is it ready for prime time?: Commentary on an article by
      Stefano Gumina, MD, PhD, et al.: "Use of platelet-leukocyte membrane in
      arthroscopic repair of large rotator cuff tears. A prospective randomized study".

PMID- 22855004
TI  - Are cognitive distortions associated with denial and minimization among sex
      offenders?
AB  - Although there has been much speculation about the relationship between cognitive
      distortions and denial/minimization, little research on the subject is available.
      The authors conducted secondary analyses on existing data sets to further examine
      the degree of association between various measures of cognitive distortions and
      denial/minimization among child molesters (Sample 1, n = 73; Sample 2, n = 42;
      Sample 3, n = 38) and rapists (Sample 1, n = 41; Sample 3, n = 14). Meta-analysis
      of the findings from Samples 1, 2, and 3 indicated that greater endorsement of
      cognitive distortions about sex offending in general was significantly associated
      with greater denial/minimization of one's own guilt and deviance (r = .24), harm
      to one's own victims (r = .32), one's need for treatment (r = .21), and
      responsibility for one's sex offenses (r = .16). Although correlated, cognitive
      distortions and denial/minimization, at least as typically measured, are distinct
      constructs.

PMID- 22855005
TI  - Can Circles of Support and Accountability (COSA) work in the United States?
      Preliminary results from a randomized experiment in Minnesota.
AB  - In 2008, the Minnesota Department of Corrections implemented Minnesota Circles of
      Support and Accountability (MnCOSA), a sex offender reentry program based on the
      Circles of Support and Accountability (COSA) model developed in Canada during the
      1990s. Using a randomized experimental design, this study evaluates the
      effectiveness of MnCOSA by conducting a cost-benefit analysis and comparing
      recidivism outcomes in the MnCOSA (N = 31) and control groups (N = 31). Despite
      the small total sample size (N = 62), the results from Cox regression models
      suggest that MnCOSA significantly reduced three of the five recidivism measures
      examined. By the end of 2011, none of the MnCOSA offenders had been rearrested
      for a new sex offense compared with one offender in the control group. Because of
      less recidivism observed among MnCOSA participants, the results from the cost
      benefit analysis show the program has produced an estimated US$363,211 in costs
      avoided to the state, resulting in a benefit of US$11,716 per participant. For
      every dollar spent on MnCOSA, the program has generated an estimated benefit of
      US$1.82 (an 82% return on investment).

PMID- 22855006
TI  - Drug-induced hypersensitivity syndrome induced by clindamycin.

PMID- 22855007
TI  - Health care utilization in the first year of life among small- and large- for
      gestational age term infants.
AB  - The objective of the study was to assess if small- and large-for gestational age
      term infants have greater health care utilization during the first year of life.
      The sample included 28,215 singleton term infants (37-42 weeks) without major
      birth defects delivered from 1998 through 2007 and continuously enrolled at
      Kaiser Permanente Northwest for 12 months after delivery. Birth weight for
      gestational age was categorized into 3 levels: <10th percentile (SGA), 10-90th
      percentile (AGA), >90th percentile (LGA). Length of delivery hospitalization, re
      hospitalizations and sick/emergency room visits were obtained from electronic
      records. Logistic regression models estimated associations between birth weight
      category and re-hospitalization. Generalized linear models estimated adjusted
      mean number of sick/emergency visits. Among term infants, 6.2 % were SGA and 13.9
      % were LGA. Of infants born by cesarean section, SGA infants had 2.7 higher odds
      [95 % 1.9, 3.8] than AGA infants of staying >=5 nights during the delivery
      hospitalization; of those born vaginally, SGA infants had 1.5 higher adjusted
      odds [95 % 1.1, 2.1] of staying >=4 nights. LGA compared to AGA infants had
      higher odds of re-hospitalization within 2 weeks of delivery [OR 1.25, 95 % CI
      0.99, 1.58] and of a length of stay >=4 days during that hospitalization [OR 2.6,
      95 % CI 1.3, 5.0]. The adjusted mean number of sick/emergency room visits was
      slightly higher in SGA (7.8) than AGA (7.5) infants (P < .05). Term infants born
      SGA or LGA had greater health care utilization than their counterparts, although
      the increase in utilization beyond the initial delivery hospitalization was
      small.

PMID- 22855008
TI  - Pemphigus with thymoma improved by thymectomy: report of a case.
AB  - A 53-year-old female with pemphigus vulgaris received treatment with prednisolone
      for 3 years. On chest computed tomography performed at follow-up, an anterior
      mediastinal tumor (4 cm * 3 cm) was detected and diagnosed as a thymoma. Although
      amyosthenia was absent, the patient's anti-acetylcholine-receptor antibody level
      was high, and she was positive for anti-desmoglein 3 antibodies. She underwent
      extended thymectomy in the same year, following which both the anti-acetylcholine
      receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The
      patient's skin symptoms improved, and the steroid dose was gradually lowered and
      finally discontinued 4 years postoperatively. Extended thymectomy may be an
      effective therapy for treating patients with pemphigus.

PMID- 22855010
TI  - Pancreaticoduodenectomy in portal annular pancreas: report of a case.
AB  - Portal annular pancreas (PAP) is a rare anatomical anomaly in which the
      pancreatic parenchyma surrounds the superior mesenteric vein and portal vein (PV)
      annularly. This anomaly requires careful consideration in pancreatic resection. A
      case is presented and the technical issues are discussed. A 61-year-old female
      was referred to the hospital for suspected papilla Vater adenocarcinoma.
      Preoperative computed tomography showed that the PV was annularly surrounded by
      pancreatic parenchyma. Surgery revealed the uncinate process extended extensively
      behind the PV and fused with the pancreatic body. The pancreas was first divided
      above the PV, and it was divided again in the body after liberating the PV from
      pancreatic annulation. The postoperative course was uneventful without pancreatic
      fistula. It is safer to divide the pancreatic body on the left of the fusion
      between the uncinate process and the pancreatic body to reduce the risk of
      pancreatic fistula in pancreaticoduodenectomy for PAP.

PMID- 22855012
TI  - Doctors targeted.
AB  - The Federal Trade Commission (FTC) has decided to get involved in scope-of
      practice issues. South Carolina dental regulators have already felt the FTC's
      wrath. That worries organized medicine and state licensing boards. They fear the
      powerful agency may place a higher value on competition than on patient safety.

PMID- 22855009
TI  - Recognition of other organ involvement might assist in the differential diagnosis
      of IgG4-associated sclerosing cholangitis without apparent pancreatic
      involvement: report of two cases.
AB  - IgG4-associated sclerosing cholangitis (IAC) was recently defined as biliary
      involvement of IgG4-related systemic disease. It is frequently associated with
      autoimmune pancreatitis, characterized by pancreatic enlargement and irregular
      narrowing of the pancreatic duct. However, a few cases of IAC with no apparent
      pancreatic involvement have been described, the characteristics of which may
      mimic those of cholangiocarcinoma. We report two rare cases of IgG4-associated
      sclerosing cholangitis at the hepatic hilum, mimicking hilar cholangiocarcinoma.
      When trying to establish the diagnosis, we should consider other organs that
      could be involved, such as the pancreas, salivary glands, retroperitoneum, lymph
      nodes, and kidneys, as well as chronic inflammatory changes. By recognizing these
      lesions and measuring serum IgG4, IAC can be diagnosed correctly, thereby
      avoiding unnecessary major surgery for a condition that is treated effectively by
      steroid therapy.

PMID- 22855011
TI  - Intrapleural chemotherapy improves the survival of non-small cell lung cancer
      patients with positive pleural lavage cytology.
AB  - PURPOSE: Information regarding the treatment of pleural lavage cytology (PLC)
      positive patients is still limited. This study evaluated the efficacy of
      intrapleural chemotherapy (IPC) in PLC-positive patients. METHODS: Three hundred
      eighty-six of the 567 lung cancer patients who underwent surgery had undergone
      PLC after thoracotomy, following by a complete resection were evaluated. IPC was
      performed after surgery, and cisplatin or adriamycin was injected intrapleurally
      through the thoracic tube. RESULTS: The pathological diagnosis showed that 17
      patients (4.4 %) were positive for (or suspected to have) malignancy in their
      PLC. The univariate and multivariate analysis showed that only pleural invasion
      was a significant predictor of a PLC-positive status. The 5-year overall survival
      in PLC-positive patients was 38 % and that in PLC-negative patients was 84 %.
      Both the univariate (p < 0.01) and multivariate (p = 0.045) analyses showed that
      the status of PLC was significantly associated with the overall survival. Eight
      of the 17 PLC-positive patients underwent IPC. The 2-year OS rate in the patients
      treated with IPC was 88 % and that of those without IPC was 44 (p = 0.04).
      CONCLUSION: IPC improved the postoperative survival in PLC-positive NSCLC
      patients, and a further prospective evaluation regarding this therapy is
      warranted.

PMID- 22855013
TI  - Lifesaving shots.
AB  - Unfortunately, low rates of influenza immunization among health care workers
      contribute to some influenza outbreaks in hospitals and long-term care
      facilities. The Texas Medical Association believes the hospital should be a place
      where people go to get better, not a place where they should worry about
      contracting a vaccine-preventable disease. TMA policy strongly endorses
      immunizing all physicians with the recommended vaccines available for
      preventable, communicable diseases.

PMID- 22855014
TI  - Avoiding the courthouse.
AB  - Four human resources topics commonly generate lawsuits for physicians: covenants
      not to compete, discrimination, independent contractor status, and disruptive
      physician behavior. A customized manual in a physician's practice can aid in
      effective communication and in implementing human resources policies and
      procedures.

PMID- 22855016
TI  - Making Aetna responsible.

PMID- 22855015
TI  - Keep insurers honest.
AB  - A law that the Texas Medical Association worked hard to pass in 2009 requires
      insurers' physician-ranking programs to use nationally recognized standards and
      guidelines and requires insurance plans to disclose those measurements to
      physicians before the evaluation period. It also gives physicians the right to
      dispute their rankings before insurers publish or advertise them to the public.
      TMA officials say most of the major plans suspended their ranking programs after
      the law was passed. But some of those insurance companies are preparing to roll
      out updated versions of their ranking programs early next year. TMA officials say
      physicians need to be aware of their rights and how to appeal any adverse
      rankings under the law.

PMID- 22855017
TI  - New rules.

PMID- 22855018
TI  - What the Joint Admission Medical Program (JAMP) can do for Texas physicians; what
      Texas physicians can do for JAMP.
AB  - Texas faces health challenges requiring a physician workforce with understanding
      of a broad range of issues -- including the role of culture, income level, and
      health beliefs -- that affect the health of individuals and communities. Building
      on previous successful physician workforce "pipeline" efforts, Texas established
      the Joint Admission Medical Program (JAMP), a first-of-its-kind program to
      encourage access to medical education by Texans who are economically
      disadvantaged. The program benefits those from racial and ethnic minority groups
      and involves all 31 public and 34 private Texas undergraduate colleges and
      universities offering life science degrees, as well as all 9 medical schools.
      Available program data indicate that JAMP has broadened enrollment diversity in
      Texas' medical schools. However, greater progress requires strengthened
      partnerships with professional colleagues practicing medicine in communities
      across Texas. This article explores how JAMP can help Texas physicians and how
      Texas physicians can help JAMP.

PMID- 22855019
TI  - Clinical and histopathological features of a suspected case of fish-eye disease.
AB  - PURPOSE: To report the clinical and histopathological features of a suspected
      case of fish-eye disease. CASE: A 57-year-old man presented with blurred vision.
      The best corrected visual acuity was 0.8 OD and 1.0 OS. The patient had no family
      history of cloudy cornea. Slit-lamp examination revealed massive bilateral
      diffuse corneal clouding. Because of progressive corneal clouding during the
      previous 3 years, we performed penetrating keratoplasty and cataract surgery. He
      had a low-plasma, high-density lipoprotein (HDL) concentration.
      Histopathologically, numerous small vacuoles were dispersed, especially in the
      anterior corneal stroma. An electron microscope revealed distinct 0.2-3.0-MUm
      lipid vacuoles with a conserved stromal structure. CONCLUSION: We suspected a
      case of sporadic fish-eye disease in a Japanese patient. Lipid deposition needs
      to be considered as a cause of diffuse corneal opacity.

PMID- 22855021
TI  - Effect on corneal shape of suturing the scleral wound during 23-gauge vitreous
      surgery.
AB  - PURPOSE: We investigated the effects on corneal shape of suturing the scleral
      wound during 23-gauge vitreous surgery. METHODS: We used a corneal topographic
      modeling system to measure the corneal shape in 39 eyes of 39 patients before and
      at 1 week, 1 month, and 3 months after performing 23-gauge vitreous surgery. We
      investigated the immediate postoperative changes and the postoperative changes
      over time according to whether suturing was performed. Suturing of the scleral
      wound was required in 20 eyes of 20 patients (suture group) and was not performed
      in 19 eyes of 19 patients (no-suture group). Spherical equivalent, regular
      astigmatism, asymmetry, and higher order irregularity components were
      investigated separately using Fourier analysis of corneal shape data obtained
      from the topographic modeling system. RESULTS: The no-suture group showed no
      significant change in any component at any point after surgery. In the suture
      group, spherical equivalent, regular astigmatism, asymmetry, and higher order
      irregularities were all increased 1 week postoperatively, but by 1 month
      postoperatively, these had all returned to their preoperative states.
      CONCLUSIONS: If suturing is required during 23-gauge vitreous surgery, patients
      should be monitored with the understanding that changes in refractive value may
      occur during the month after surgery owing to changes in corneal shape.

PMID- 22855020
TI  - The role of fibronectin in corneal wound healing explored by a physician
      scientist.
AB  - For the past 30 years, I have worked as a physician-scientist in both the clinic
      and laboratory setting at a number of university medical schools. Encountering
      patients in the clinic for whom treatment was not available led me to the
      laboratory in an attempt to develop the appropriate treatment for future
      patients. The main focus of my translational research has been the role of
      fibronectin in corneal epithelial wound healing and the development of
      fibronectin eyedrops for the treatment of patients with persistent corneal
      epithelial defects. An extension of this research led to the development of
      eyedrops containing the synthetic peptide proline-histidine-serine-arginine
      asparagine (PHSRN), which corresponds to the second cell-binding site of
      fibronectin. My clinical experience with fibronectin eyedrops also prompted me to
      examine the role of the sensory neurotransmitter substance P and insulin-like
      growth factor-1 (IGF-1) in corneal wound healing, leading to the development of
      eyedrops containing peptides derived from these agents (peptides FGLM-amide and
      SSSR, respectively). Although the path from the laboratory to the clinic in these
      instances has been relatively short, the time required to establish the newly
      identified treatment modalities in the wider community has been long. In this
      review, I relate the trajectory of my translational research career.

PMID- 22855022
TI  - Pathological findings of infraorbital nerve enlargement in IgG4-related
      ophthalmic disease.
AB  - PURPOSE: We report a case of bilateral infraorbital nerve enlargement (IONE)
      associated with immunoglobulin (Ig)G4-related ophthalmic disease and describe the
      associated histopathologic findings. CASE: An otherwise healthy 59-year-old man
      presented with bilateral exophthalmos and right visual disturbance. Orbital
      magnetic resonance imaging showed bilateral IONE and a soft tissue mass in the
      right orbit. Excisional biopsy in the left infraorbital canal was performed.
      Histopathologic assessment revealed IgG4-related disease involving the epineurium
      of the infraorbital nerve. The patient received systemic steroid therapy, to
      which he responded well. CONCLUSION: IONE in IgG4-related ophthalmic disease is
      due to IgG4-related disease involving the epineurium.

PMID- 22855023
TI  - Prognostic risk factors for failure of trabeculectomy with mitomycin C after
      vitrectomy.
AB  - PURPOSE: To evaluate the prognostic risk factors for failure of trabeculectomy
      with mitomycin C (MMC) in vitrectomized eyes. METHODS: Retrospective cohort
      study. We reviewed the medical records of 116 patients (116 eyes) treated at
      Kumamoto University Hospital. The primary endpoints were persistent intraocular
      pressure of >21 mmHg, deterioration of visual acuity to no light perception, or
      additional glaucoma procedures. Multivariable analysis was performed with the Cox
      proportional hazards model. RESULTS: The mean follow-up period was 36.5 months
      (range, 0.5-134.1 months). The probability of success 1 year after trabeculectomy
      was 55.1 %, 2 years after was 45.3 %, and 3 years after was 43.1 %. The
      multivariable model showed that higher preoperative intraocular pressure (IOP)
      [relative risk (RR), 1.05/mmHg; P = 0.0077] and neovascular glaucoma (NVG) (RR,
      1.88; P = 0.049) were prognostic factors for surgical failure. CONCLUSIONS: The
      prognostic factors for surgical failure of trabeculectomy with MMC in
      vitrectomized eyes are a higher preoperative IOP and NVG.

PMID- 22855024
TI  - Polymorphisms in folate-metabolizing genes and risk of having an offspring with
      congenital anomalies in the West Siberian region of Russia: a case-control study.
AB  - OBJECTIVE: Periconceptional folate supplementation prevents a number of
      congenital anomalies (CA). The aim of our study was to investigate the
      association of 11 polymorphisms in the folate-metabolizing genes with the risk of
      having an offspring with CA in the Russian ethnic group. METHOD: We genotyped 280
      mothers having a CA-affected pregnancy and 390 control mothers. The most common
      malformations among the cases were CA of the nervous, urinary, and cardiovascular
      systems, and these groups were analyzed separately. RESULTS: In the whole group
      of CA, we revealed the associations of MTHFR C677T and MTR A2756G loci with
      increased risk of CA-affected pregnancy. In the group of CA of the cardiovascular
      system, we observed an association of MTHFR A1298C with decreased risk and an
      association of MTR A2756G with increased risk of CA. After the Bonferroni
      correction, only the association between the genotype MTR 2756GG and the risk of
      having a fetus with CA of the cardiovascular system remained statistically
      significant (OR = 4.99, P = 0.03). CONCLUSION: These findings indicate that locus
      A2756G in the MTR gene may play a role in susceptibility to CA of the
      cardiovascular system in West Siberia, but further research is necessary to
      confirm the association.

PMID- 22855025
TI  - Synthesis and evaluation of inhibitors of E. coli PgaB, a polysaccharide de-N
      acetylase involved in biofilm formation.
AB  - Many medically important biofilm forming bacteria produce similar polysaccharide
      intercellular adhesins (PIA) consisting of partially de-N-acetylated beta-(1 ->
      6)-N-acetylglucosamine polymers (dPNAG). In Escherichia coli, de-N-acetylation of
      the beta-(1 -> 6)-N-acetylglucosamine polymer (PNAG) is catalysed by the
      carbohydrate esterase family 4 deacetylase PgaB. The de-N-acetylation of PNAG is
      essential for productive PNAG-dependent biofilm formation. Here, we describe the
      development of a fluorogenic assay to monitor PgaB activity in vitro and the
      synthesis of a series of PgaB inhibitors. The synthesized inhibitors consist of a
      metal chelating functional group on a glucosamine scaffold to target the active
      site metal ion of PgaB. Optimal inhibition was observed with N-thioglycolyl amide
      (K(i) = 480 MUM) and N-methyl-N-glycolyl amide (K(i) = 320 MUM) glucosamine
      derivatives. A chemoenzymatic synthesis of an N-thioglycolyl amide PNAG
      pentasaccharide led to an inhibitor with an improved K(i) of 280 MUM.

PMID- 22855026
TI  - Rothstein Roundtable Podcast--"Medical Homes, PACA, IFDS--Where do physical
      therapists fit in a reforming health care environment? ".

PMID- 22855027
TI  - Exploration of the active site of Escherichia coli cystathionine gamma-synthase.
AB  - Cystathionine gamma-synthase (CGS) catalyzes the condensation of O-succinyl-L
      homoserine (L-OSHS) and L-cysteine (L-Cys), to produce L-cystathionine (L-Cth)
      and succinate, in the first step of the bacterial transsulfuration pathway. In
      the absence of L-Cys, the enzyme catalyzes the futile alpha,gamma-elimination of
      L-OSHS, yielding succinate, alpha-ketobutyrate, and ammonia. A series of 16 site
      directed variants of Escherichia coli CGS (eCGS) was constructed to probe the
      roles of active-site residues D45, Y46, R48, R49, Y101, R106, N227, E325, S326,
      and R361. The effects of these substitutions on the catalytic efficiency of the
      alpha,gamma-elimination reaction range from a reduction of only ~2-fold for R49K
      and the E325A,Q variants to 310- and 760-fold for R361K and R48K, respectively. A
      similar trend is observed for the k(cat) /K(m)(l-OSHS) of the physiological,
      alpha,gamma-replacement reaction. The results of this study suggest that the
      arginine residues at positions 48, 106 and 361 of eCGS, conserved in bacterial
      CGS sequences, tether the distal and alpha-carboxylate moieties, respectively, of
      the L-OSHS substrate. In contrast, with the exception of the 13-fold increase
      observed for R106A, the K(m)(l-Cys) is not markedly affected by the site-directed
      replacement of the residues investigated. The decrease in k(cat) observed for the
      S326A variant reflects the role of this residue in tethering the side chain of
      K198, the catalytic base. Although no structures exist of eCGS bound to active
      site ligands, the roles of individual residues is consistent with the structures
      inhibitor complexes of related enzymes. Substitution of D45, E325, or Y101
      enables a minor transamination activity for the substrate L-Ala.

PMID- 22855028
TI  - Impact of acute lung injury and acute respiratory distress syndrome after
      traumatic brain injury in the United States.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability,
      morbidity, and mortality. The effect of the acute respiratory distress syndrome
      and acute lung injury (ARDS/ALI) on in-hospital mortality after TBI remains
      controversial. OBJECTIVE: To determine the epidemiology of ARDS/ALI, the
      prevalence of risk factors, and impact on in-hospital mortality after TBI in the
      United States. METHODS: Retrospective cohort study of admissions of adult
      patients>18 years with a diagnosis of TBI and ARDS/ALI from 1988 to 2008
      identified through the Nationwide Inpatient Sample. RESULTS: During the 20-year
      study period, the prevalence of ARDS/ALI increased from 2% (95% confidence
      interval [CI], 2.1%-2.4%) in 1988 to 22% (95% CI, 21%-22%) in 2008 (P<.001).
      ARDS/ALI was more common in younger age; males; white race; later year of
      admission; in conjunction with comorbidities such as congestive heart failure,
      hypertension, chronic obstructive pulmonary disease, chronic renal and liver
      failure, sepsis, multiorgan dysfunction; and nonrural, medium/large hospitals,
      located in the Midwest, South, and West continental US location. Mortality after
      TBI decreased from 13% (95% CI, 12%-14%) in 1988 to 9% (95% CI, 9%-10%) in 2008
      (P<.001). ARDS/ALI-related mortality after TBI decreased from 33% (95% CI, 33%
      34%) in 1988 to 28% (95% CI, 28%-29%) in 2008 (P<.001). Predictors of in-hospital
      mortality after TBI were older age, male sex, white race, cancer, chronic kidney
      disease, hypertension, chronic liver disease, congestive heart failure, ARDS/ALI,
      and organ dysfunctions. CONCLUSION: Our analysis demonstrates that ARDS/ALI is
      common after TBI. Despite an overall reduction of in-hospital mortality, ARDS/ALI
      carries a higher risk of in-hospital death after TBI.

PMID- 22855029
TI  - alpha-Amination of aldehydes catalyzed by in situ generated hypoiodite.
AB  - The metal-free amination of different aldehydes is catalyzed by hypoiodite, which
      is generated by employing commercially available sodium percarbonate as the co
      oxidant. This approach has several advantages: it is a metal-free oxidation that
      works under mild reaction conditions; furthermore, it has a wide substrate scope
      and does not give toxic by-products from the co-oxidant that is used.

PMID- 22855031
TI  - Treatment of neuropathic pain with plant medicines.
AB  - Neuropathic pain is a common and very prevalent disorder affecting the citizens
      of both developed and developing countries. The approved and licensed drugs for
      neuropathic pain are reported to have associated side effects. Traditional plant
      treatments have been used throughout the world for the treatment of neuropathic
      pain. Among the many medications and other alternative medicines, several herbs
      are known to cure and control neuropathic pain with no side effects. The present
      paper discusses the plants with neuropathic pain and related beneficial effects
      originating from different parts of world that are of current interest.

PMID- 22855030
TI  - Stearoyl-acyl carrier protein desaturase gene from the oleaginous microalga
      Chlorella zofingiensis: cloning, characterization and transcriptional analysis.
AB  - The green alga Chlorella zofingiensis can accumulate high level of oleic acid
      (OA, C18:1?(9)) rich oils in response to stress conditions. To understand the
      regulation of biosynthesis of fatty acid in particular OA at the molecular level,
      we cloned and characterized the stearoyl acyl carrier protein (ACP) desaturase
      (SAD) responsible for OA formation through desaturation of stearic acid (C18:0)
      from C. zofingiensis. Southern blot indicated that the C. zofingiensis genome
      contained a single copy of SAD, from which the deduced amino acid sequence shared
      high identity to the corresponding homologs from other microalgae and higher
      plants. The desaturation activity of SAD was demonstrated in vitro using C18:0
      ACP as a substrate. Stress conditions such as high light (HL), nitrogen
      deficiency (N(-)), or combination of HL and N(-) (HL + N(-)) drastically up
      regulated the transcripts of biotin carboxylase (BC, a subunit of ACCase) and
      SAD, and therefore induced considerably the cellular accumulation of total fatty
      acids including OA. Glucose (50 mM) gave rise to the similar up-regulation of the
      two genes and induction of fatty acid accumulation. The accumulation of
      intracellular reactive oxygen species was found to be associated with the up
      regulation of genes. This is the first report of characterization of Chlorella
      derived SAD and the results may contribute to understanding of the mechanisms
      involved in fatty acid/lipid biosynthesis in microalgae.

PMID- 22855032
TI  - Several considerations in using traditional Chinese patent medicine for cerebral
      infarction.
AB  - Nowadays, a great number of traditional Chinese patent medicine (TCPM) are used
      more and more widely to treat cerebral infarction in China. When great attention
      is paid to using TCPM in the real world, several problems can be identified:
      ignoring the Chinese medicine (CM) therapeutic principle based on syndrome
      differentiation, a lack of appropriate dosage and usage based on individual
      patient conditions, and a shortage of evidence from randomized, double-blind,
      placebo-controlled clinical trials. Furthermore, in terms of evaluation of the
      TCPM effectiveness, few comprehensive criteria and evaluation methods recognized
      by the international community exist. This article addresses some opinions
      regarding the above mentioned problems.

PMID- 22855033
TI  - Logistic regression analysis of damp-heat and cold-damp impeding syndrome of
      rheumatoid arthritis: a perspective in Chinese medicine.
AB  - OBJECTIVE: To investigate a method for quantitative differential diagnosis of
      damp-heat and cold-damp impeding syndrome of rheumatoid arthritis (RA) in Chinese
      medicine (CM). METHODS: Laboratory parameters were collected from 306 patients
      with RA. The clinical symptoms and laboratory parameters were compared between
      patients with these two syndromes (158 with RA of damp-heat impeding syndrome,
      and 148 with RA of cold-damp impeding syndrome), and a regression equation was
      established to facilitate discrimination of the two RA syndromes. RESULTS: There
      were significant differences in disease activity score in 28 joints [DAS28 (4)],
      erythrocyte sedimentation rate (ESR), white blood cell count (WBC), C-reactive
      protein (CRP), platelet count (PLT), albumin (ALB) and globulin (GLB) between the
      two syndrome of RA (P<0.05). Logistic regression analysis showed that the
      parameters ESR, WBC, CRP, joint pyrexia, joint cold, thirst, sweating, aversion
      to wind and cold, and cold extremities were statistically useful to discriminate
      damp-heat from cold-damp impeding syndrome. The regression equation was as
      follows: P=1/{1+exp[-(3.0-0.021X (1)-0.196X (2)-0.163X (3)-1.559X (4)+1.504X (5)
      0.927X (6)-1.039X (7)+1.070X (8)+1.330X (9))]}. The independent variables X (1)-X
      (9) were ESR, WBC, CRP, hot joint, cold joint, thirst, sweating, aversion to wind
      and cold, and cold limbs. A P value > 0.5 signified cold-damp impeding syndrome,
      and a P value < 0.5 signified damp-heat impeding syndrome. The accuracy was
      90.2%. CONCLUSION: The regression equation may be useful for discriminating damp
      heat from cold-damp impeding syndrome of RA.

PMID- 22855034
TI  - Effect of extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong
      on delaying aging of vascular smooth muscle cells in aged rats.
AB  - OBJECTIVE: To observe the effect of extracts from Radix Ginseng, Radix
      Notoginseng and Rhizoma Chuanxiong (EXT) on delaying vascular smooth muscle cells
      (VSMCs) aging in aged rats. METHODS: VSMCs were obtained by the modified tissue
      explants technique and were shown to be positive for smooth muscle alpha-actin
      (SM-alpha-actin) by immunohistochemistry staining. VSMCs obtained from the young
      rats were served as the young control group; VSMCs obtained from the old rats
      were treated with no drug (the old group), with low dose extracts (20 mg/L, the
      EXT low-concentration group) and high dose extracts (40 mg/L, the EXT high
      concentration group), and with Probucal (10(-6) mol/L, the Probucal group) as a
      positive control. All groups were cultured for 24 h in the medium with 10% serum
      for 24 h followed by another 24 h in the serum-free medium. At the end of the 48
      h culture, the following analyses were performed including determination of
      senescence-associated beta-galactosidase (SAbeta-Gal) activity, flow cytometry
      analysis of cell cycle, real-time quantitative reverse transcription polymerase
      chain reaction (RT-PCR) analyses of p16, Cyclin D1, cyclin-dependent kinase 4
      (CDK4) and retinoblastoma (Rb) mRNA expression, and Western blotting analyses of
      p16, cyclin D1, CDK4 and phosphoretinoblastoma (pRb) protein expressions.
      RESULTS: (1) In comparison to the younger rats, VSMCs from aged rats had
      significantly more SAbeta-Gal positive cells (P<0.01) and more cells in S phase
      (P<0.05). VSMCs from the all treated groups showed a significant decrease in both
      SAbeta-Gal positive cells (P<0.05) and S phase (P<0.05) compared to the old rats.
      (2) Compared with the young group, VSMCs in the old group had a significant
      decrease in p16 and Rb mRNA expression and a significant increase in Cyclin D1
      and CDK4 mRNA expression. Compared with the old group, VSMCs in the treated
      groups had a significant increase in p16 and Rb mRNA expression and a significant
      decrease in Cyclin D1 and CDK4 mRNA expression (P<0.05). (3) Compared with the
      young group, VSMCs in the old group had a significant decrease in p16 protein
      expression and a significant increase in Cyclin D1, CDK4 and pRb protein
      expressions (P<0.05). Compared with the old group, VSMCs in the treated groups
      had a significant increase in p16 protein expression and a significant decrease
      in cyclinD1, CDK4 and pRb protein expressions (P<0.05). CONCLUSIONS: VSMCs
      obtained from old rats showed typical signs of cellular senescence and vascular
      aging. EXT had an effect on delaying senescence of VSMCs in vitro by altering the
      p16-cyclinD/CDK-Rb pathway.

PMID- 22855035
TI  - Effects of brucine on vascular endothelial growth factor expression and
      microvessel density in a nude mouse model of bone metastasis due to breast
      cancer.
AB  - OBJECTIVE: To study the effects of brucine on vascular endothelial growth factor
      (VEGF) expression and microvessel density (MVD) in a nude mouse model of bone
      metastasis due to breast cancer, and to assess the possible antitumor mechanism
      of brucine. METHODS: A syringe needle was used to directly inject 0.2 mL
      monoplast suspension (with 2*10(5) human breast cancer cells contained) into the
      bony femoral cortex of the right hind leg for modeling. Twenty-five nude mice
      were randomized into five groups and administered with an intraperitoneal
      injection of saline or drug for 8 consecutive days: model group (0.2 mL normal
      saline), low-dose brucine group (1.73 mg.kg(-1)), medium-dose brucine group (3.45
      mg.kg(-1)), high-dose brucine group (6.90 mg.kg(-1)), and thalidomide group (200
      mg.kg(-1)). Diet and activity were recorded, and the tumors were harvested 5
      weeks later. The percentage of VEGF-positive cells was determined with
      hematoxylin and eosin staining and immunohistochemical staining, and MVD
      expression was determined by optical microscopy. RESULTS: The VEGF expressions in
      brucine- or thalidomide-treated mice were significantly reduced as compared with
      mice in the model group (P <0.01). There were no significant difference between
      the high-dose brucine group and the thalidomide group (P >0.05). Significant
      difference was between the high- and low-dose brucine group P<0.05). Further,
      VEGF expression was significantly increased in the low- and medium-dose brucine
      groups compared with the thalidomide group (P <0.05). The MVD values in the three
      brucine and thalidomide groups were significantly lower than that in the model
      group (P <0.01). The MVD values in the medium- and high-dose brucine groups were
      not significantly different from those in the thalidomide group (P >0.05), while
      the MVD value showed a significant increase in the low-dose group compared with
      the thalidomide group (P <0.05). CONCLUSION: Brucine could inhibit the growth of
      breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.

PMID- 22855036
TI  - Effects of tetramethylpyrazine on cardiac function and mortality rate in septic
      rats.
AB  - OBJECTIVE: To study the effects of tetramethylpyrazine (TMP) on cardiac function
      and mortality rate in septic rats. METHODS: Fifty male Sprague-Dawley rats were
      randomized into a sham-operation group (sham group, n=10), normal saline group
      (NS group, n=20), and TMP group (n=20). The rats in the NS and TMP groups
      underwent cecal ligation and puncture (CLP) to induce sepsis. Rats in the NS
      group were injected with NS (10 mL/kg) immediately after CLP and 6 h after CLP.
      Rats in the TMP group were injected with TMP (10 mg/kg) at the same time points.
      Twenty-four hours after modeling, the mortality rates were observed in each
      group. Cardiac function and serum concentration of tumor necrosis factor alpha
      (TNF-alpha) were also tested. The correlation between TNF-alpha and the ejection
      fraction (EF) was observed. Left ventricle specimens were reserved for
      histomorphologic study. RESULTS: Compared with the sham group, the NS and TMP
      groups had decreased EF values and increased mortality rates and serum TNF-alpha
      levels (P <0.05). The TMP group had a comparatively lower mortality rate and TNF
      alpha level and a higher EF value compared with the NS group (P <0.05).
      Histomorphology indicated that myocardial inflammation in the TMP group was mild
      compared with that in the NS group. There was a negative correlation between TNF
      alpha level and EF value (r=-0.583,P=0.000). CONCLUSION: TMP could reduce the
      mortality rate of septic rats and had certain protective effects on cardiac
      function.

PMID- 22855037
TI  - Effects of Panax notoginseng saponins on proliferation and differentiation in
      NIH3T3 cells.
AB  - OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on the
      proliferation and differentiation in NIH3T3 cells. METHODS: NIH3T3 cells were
      treated by various concentrations of PNS 0, 0.05, 0.10, 0.20, and 0.40 g/L. The
      vitality and proliferation potential of cells were detected by 3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the alkaline
      phosphatase (ALP) activity was measured by p-nitrophenyl phosphate (pNPP) assay,
      and the mineralization formation ability was tested for the cellular
      differentiation toward osteoblast, as well as the expression level of
      phosphorylated extracellular signal-regulated kinase1/2(P-ERK1/2), extracellular
      signal-regulated kinase1/2 (ERK1/2) protein kinase was analyzed by Western blot
      with total cell lysate of NIH3T3 cells treated by PNS. RESULTS: Both MTT and pNPP
      assay showed that optical density (OD) values were increased in response to PNS
      treatment at a dose-dependent pattern. The mineralization formation ability was
      enhanced in PNS-treated NIH3T3 cells compared with untreated cells. Meanwhile,
      the expression level of P-ERK1/2 protein kinase was up-regulated in PNS-treated
      NIH3T3 cells, while, the expression level of ERK1/2 protein kinase revealed no
      obvious difference with or without PNS treated cells. CONCLUSION: PNS could pay a
      role to promote the proliferation and differentiation in NIH3T3 cells by means of
      up-regulation of P-ERK1/2 protein kinase.

PMID- 22855038
TI  - A randomized controlled trial comparing total glucosides of paeony capsule and
      compound glycyrrhizin tablet for alopecia areata.
AB  - OBJECTIVE: To observe the efficacy and safety of total glucosides of paeony
      capsule (TGPC) in patients with mild and moderate alopecia areata. METHODS: A
      total of 86 outpatients were randomly allocated into two groups of TGPC
      (treatment, 44 cases) and compound glycyrrhizin tablet (control, 42 cases). The
      treatment group was given oral TGPC, three times daily and 600 mg per time; the
      control group was given oral compound glycyrrhizin tablets, three times daily and
      50 mg per time. In addition, both groups were given 10 mg of vitamin B(2) and
      tapped the bold patches with massage. The treatment course was three months for
      both groups. Peripheral blood T-cell subsets (CD3(+)CD4(+), CD3(+)CD8(+), Th, Ts,
      Th/Ts) of 10 patients randomly selected from each group respectively were tested
      before and after three months of treatment. The effectiveness and adverse
      reaction of all cases were observed each month. The safety was evaluated
      according to the incidence rate of adverse reaction. RESULTS: In the treatment
      group, the cured and markedly effective rate was 36.36% (16/44), 50.00% (22/44)
      and 68.18% (30/44) at the end of first, second and third month of treatment,
      respectively, and the incidence rate of adverse reaction was 13.64% (6/44). In
      the control group, the cured and markedly effective rate was 38.10% (16/42),
      57.14% (24/42) and 71.43% (30/42), respectively, and the incidence rate of
      adverse reaction was 16.67% (7/42). The cured and markedly effective rate and the
      incidence rate of adverse reaction were similar in both groups (P>0.05). TGPC and
      compound glycyrrhizin tablet can inhibit CD3(+)CD4(+) and CD3(+)CD8(+), and
      decrease the ratio of Th/Ts (P<0.05). CONCLUSION: TGPC is effective and safe in
      the treatment of alopecia areata.

PMID- 22855039
TI  - Longer overall survival in a patient with advanced non-small cell lung cancer
      treated with Chinese medicine and chemotherapy.

PMID- 22855040
TI  - Traditional Chinese medicine and the positive correlation with homeostatic
      evolution of human being: based on medical perspective.
AB  - Adaptation is an eternal theme of biological evolution. The paper aims at
      exploring the conception of positive correlation between traditional Chinese
      medicine (TCM) and human homeostatic evolution based on medical perspective.
      Discussions mainly involve TCM conforming to natural laws and natural evolution
      of life, spontaneous harmonization of yin and yang and operating system of human
      self-healing, modern human immunology and human endogenous immune function in
      TCM, self-homeostasis of human micro-ecological state and balance mechanism on
      regulating base in TCM, as well as adaptation-eternal theme of biological
      evolution and safeguarding adaptability-value of TCM. In perspective of medicine,
      theory and practice of TCM are in positive correlation with human homeostatic
      evolution, and what TCM tries to maintain is human intrinsic adaptive capability
      to disease and nature. Therefore, it is the core value of TCM, which is to be
      further studied, explored, realized and known to the world.

PMID- 22855041
TI  - Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral
      mucositis in head and neck cancer patients.
AB  - In recent years, more head and neck cancer patients have been treated with
      radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity
      of radiotherapy among patients with head and neck cancers. Patients undergoing
      radiation therapy for head and neck cancer are also at increased risk of
      developing oral candidiasis. A number of new agents applied locally or
      systemically to prevent or treat radiation-induced mucositis have been
      investigated, but there is no widely accepted prophylactic or effective treatment
      for mucositis. Topical Aloe vera is widely used for mild sunburn, frostbites, and
      scalding burns. Studies have reported the beneficial effects of Aloe gel for
      wound healing, mucous membrane protection, and treatment of oral ulcers, in
      addition to antiinflammatory, immunomudulation, antifungal, scavenging free
      radicals, increasing collagen formation and inhibiting collagenase. Herein the
      author postulates that oral Aloe vera mouthwash may not only prevent radiation
      induced mucositis by its wound healing and antiinflammatory mechanism, but also
      may reduce oral candidiasis of patients undergoing head and neck radiotherapy due
      to its antifungal and immunomodulatory properties. Hence, Aloe vera mouthwash may
      provide an alternative agent for treating radiation-induced oral mucositis and
      candidiasis in patients with head and neck cancers.

PMID- 22855042
TI  - Patient recall of surgical information after day case knee arthroscopy.
AB  - PURPOSE: Day case knee arthroscopy is frequently performed on dedicated lists
      designed to optimise the throughput of patients. This could affect patient recall
      of clinical information with clinical, ethical and medicolegal consequences. The
      purpose of this study was to assess patient recall after knee arthroscopy and
      identify potential contributory factors. METHODS: Seventy-two patients undergoing
      day case knee arthroscopy were provided with information about their surgery post
      operatively and tested for recall of the information prior to discharge. All
      patients underwent cognitive assessment when information was delivered and again
      when tested. Patient recall was correlated with demographic and anaesthetic
      factors and a multivariate regression model was used to identify risk factors for
      reduced recall. RESULTS: Recall overall was poor. Significant independent risk
      factors for reduced recall were reduced cognitive state at the time of
      information delivery and a shorter time between surgery and information delivery.
      Duration of anaesthesia, use of sedatives and use of opiate analgesia were not
      significantly correlated with recall. CONCLUSIONS: Information recall after day
      case knee athroscopy may be suboptimal. Allowing more time between surgery and
      information delivery may improve recall. However, this may be difficult during
      the course of a busy list and surgeons should consider using additional
      techniques to improve patient recall after surgery to reduce the risk of patient
      anxiety or non-compliance. LEVEL OF EVIDENCE: IV.

PMID- 22855043
TI  - Post-traumatic anterior impingement of the ankle.

PMID- 22855044
TI  - CrossTalk proposal: training the respiratory muscles does not improve exercise
      tolerance.

PMID- 22855045
TI  - CrossTalk opposing view: respiratory muscle training does improve exercise
      tolerance.

PMID- 22855048
TI  - Making do with what we have: use your bootstraps.

PMID- 22855049
TI  - Single myotonia mutation strikes multiple mechanisms of a chloride channel.

PMID- 22855050
TI  - The small airways accordion: concurrent or alternating fluid absorption and
      secretion?

PMID- 22855051
TI  - Sympathetic neural tone: large and in charge throughout pregnancy.

PMID- 22855052
TI  - Standing up for exercise: should deconditioning be medicalized?

PMID- 22855053
TI  - Andrew Fielding Huxley (1917-2012).

PMID- 22855055
TI  - Response to letter from Teppema and Berendsen concerning Fan et al. (2012):
      'Acetazolamide and cerebrovascular function at high altitude'.

PMID- 22855054
TI  - Protein S-glutathionylation enhances Ca2+-induced Ca2+ release via the IP3
      receptor in cultured aortic endothelial cells.
AB  - In non-excitable cells, thiol-oxidizing agents have been shown to evoke
      oscillations in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) by increasing
      the sensitivity of the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) to
      IP(3). Although thiol modification of the IP(3)R is implicated in this response,
      the molecular nature of the modification(s) responsible for changes in channel
      activity is still not well understood. Diamide is a chemical oxidant that
      selectively converts reduced glutathione (GSH) to its disulfide (GSSG) and
      promotes the formation of protein-glutathione (P-SSG) mixed disulfide, i.e.
      glutathionylation. In the present study, we examined the effect of diamide, and
      the model oxidant hydrogen peroxide (H(2)O(2)), on oscillations in [Ca(2+)](i) in
      fura-2-loaded bovine (BAECs) and human (HAECs) aortic endo-thelial cells using
      time-lapse fluorescence video microscopy. In the absence of extracellular Ca(2+),
      acute treatment with either diamide or H(2)O(2) increased the number of BAECs
      exhibiting asynchronous Ca(2+) oscillations, whereas HAECs were unexpectedly
      resistant. Diamide pretreatment increased the sensitivity of HAECs to histamine
      stimulated Ca(2+) oscillations and BAECs to bradykinin-stimulated Ca(2+)
      oscillations. Moreover, in both HAECs and BAECs, diamide dramatically increased
      both the rate and magnitude of the thapsigargin-induced Ca(2+) transient
      suggesting that Ca(2+)-induced Ca(2+) release (CICR) via the IP(3)R is enhanced
      by glutathionylation. Similar to diamide, H(2)O(2) increased the sensitivity of
      HAECs to both histamine and thapsigargin. Lastly, biochemical studies showed that
      glutathionylation of native IP(3)R(1) is increased in cells challenged with
      H(2)O(2). Collectively our results reveal that thiol-oxidizing agents primarily
      increase the sensitivity of the IP(3)R to Ca(2+), i.e. enhanced CICR, and suggest
      that glutathionylation may represent a fundamental mechanism for regulating
      IP(3)R activity during physiological redox signalling and during pathologicalical
      oxidative stress.

PMID- 22855057
TI  - Redox regulation of neurovascular function by acetazolamide: complementary
      insight into mechanisms underlying high-altitude acclimatisation.

PMID- 22855058
TI  - Expression and significance of Kruppel-like factor 6 gene in osteosarcoma.
AB  - PURPOSE: Osteosarcoma is primary malignant tumour of bone. Kruppel-like factor 6
      (KLF6) is a tumor suppressor gene frequently inactivated in a number of human
      cancers and a ubiquitously expressed zinc-finger transcription factor. The
      present study aimed to first explore the relationship between the expression
      level of the KLF6 gene in osteosarcoma and the occurrence of bone tumours.
      METHODS: KLF6 mRNA and protein expression levels in osteosarcoma and normal bone
      tissue were assayed by real-time quantitative PCR and immunohistochemistry. KLF6
      mRNA and protein expression levels in osteosarcoma cells and normal osteoblasts
      were detected by semi-quantitative reverse transcription PCR and Western
      blotting, respectively. RESULTS: Both the expression of KLF6 mRNA and protein in
      osteosarcoma cells and tissues were significantly lower than that in normal cells
      and tumour-adjacent tissues. CONCLUSIONS: KLF6 is a putative tumor suppressor
      gene involved in osteosarcoma which can be used as a new therapeutic target and
      an important marker for early diagnosis and postoperative monitoring.

PMID- 22855059
TI  - Expression of Vascular Endothelial Growth Factor correlates with the advance of
      clinical osteosarcoma.
AB  - PURPOSE: Osteosarcoma is the most common primary malignancy in orthopaedic
      surgery. Studies suggest that expression of VEGF and high vascularity within
      osteosarcoma may correlate with poor prognosis. The purpose of this study was to
      determine whether there was a correlation of VEGF expression with clinical tumour
      stage and metastasis. METHODS: This retrospective case series examined 54 cases
      of osteosarcoma patients who were treated during a ten-year period. Relevant
      clinical information included age, gender, tumour location, stage, adjuvant
      therapy, morbidity, mortality, and tumour subtypes. The clinical information was
      analysed for correlation of VEGF expression and tumour prognosis. Tumour sections
      were examined by routine H&E and by immunohistochemistry for VEGF, CD31, and the
      oncogenes c-myc and c-fos. RESULTS: There was a significantly positive
      correlation between VEGF expression and tumour stages among these cases (p <
      0.01). The data also suggested a higher cancer recurrence and more frequent cases
      of remote metastasis in the high-VEGF group compared to the low-VEGF group. VEGF
      expression also positively associated with c-fos and c-myc expressions in the
      primary tumour sections. CONCLUSION: The results of this study highlight the role
      of VEGF in angiogenesis and tumour burden. Data also suggest the influence of
      VEGF may associate with the elevations of c-fos and c-myc expression. The
      development of novel therapies to target the VEGF pathway in osteosarcoma may
      lead to improved survival.

PMID- 22855060
TI  - Mental health service use by youths in contact with child welfare: racial
      disparities by problem type.
AB  - OBJECTIVE: This study examined racial disparities in mental health service use by
      problem type (internalizing versus externalizing) for youths in contact with the
      child welfare system. METHODS: Participants included 1,693 non-Hispanic white,
      African-American, and Hispanic youths (ages four to 14) from the National Survey
      of Child and Adolescent Well-Being, a national probability study of youths who
      were the subject of investigations of maltreatment by child welfare agencies.
      Mental health need, assessed at baseline, was considered present if the youth had
      internalizing or externalizing scores in the clinical range on either the Child
      Behavior Checklist or the Youth Self-Report. Out patient mental health service
      use in the subsequent year was assessed prospectively. RESULTS: Children who were
      removed from the home and those investigated for abuse (versus neglect) were more
      likely to receive services in the year after the child welfare investigation.
      Overall, African-American youths were less likely than non-Hispanic white youths
      to receive mental health services. However, race-ethnicity moderated the
      association between externalizing need and service use such that African
      Americans were more likely to receive services when externalizing need was
      present (26% versus 4%) compared with non-Hispanic white youths (30% versus 14%).
      Race and ethnicity did not moderate the association between youth internalizing
      need and service use, but internalizing need was associated with increased
      probability of service use only for non-Hispanic white youths. CONCLUSIONS:
      Examinations of overall racial disparities in service use may obscure important
      problem specific disparities. Additional research is needed to identify factors
      that lead to disparities and to develop strategies for reducing them.

PMID- 22855063
TI  - Small-bowel endoscopy.

PMID- 22855062
TI  - Efficacy and tolerability of fixed-dose amlodipine/olmesartan medoxomil with or
      without hydrochlorothiazide in Hispanic and non-Hispanic patients whose blood
      pressure is uncontrolled on antihypertensive monotherapy.
AB  - OBJECTIVES: This is a prespecified subgroup analysis in Hispanic and non-Hispanic
      patients of a study that evaluated blood pressure (BP) control with fixed-dose
      amlodipine/olmesartan medoxomil (AML/OM)-based therapy in patients whose
      condition was uncontrolled on prior monotherapy. METHODS: In this prospective,
      open-label, dose-titration study, patients with uncontrolled BP after at least 1
      month of antihypertensive monotherapy were switched to fixed-dose AML/OM 5/20 mg.
      Patients were uptitrated to AML/OM 5/40 and 10/40 mg, with uptitration to AML/OM
      + hydrochlorothiazide 10/40 + 12.5 mg and 10/40 + 25 mg to achieve target BP. The
      primary efficacy endpoint was the cumulative proportion of patients achieving
      seated cuff systolic BP (SeSBP) less than 140 mmHg (<130 mmHg in patients with
      diabetes mellitus) at 12 weeks. Secondary endpoints included SeBP goal rates,
      ambulatory BP (ABP) target rates, and mean change from baseline in seated cuff BP
      (SeBP) and ABP at weeks 12 and 20. RESULTS: Mean baseline BP was similar in
      Hispanics (153.6/92.8 mmHg; n = 105) and non-Hispanics (153.7/91.8 mmHg; n =
      894). At 12 weeks, 72.0% of Hispanics and 76.3% of non-Hispanics achieved the
      primary endpoint. At week 12, goal rates for cumulative SeBP (<140/90 mmHg or
      <130/80 mmHg in patients with diabetes) were 69.0% and 71.5% in Hispanic and non
      Hispanic patients, respectively. Mean change in SeBP in Hispanics ranged from 
      15.3/-7.3 mmHg for AML/OM 5/20 mg to -23.2/-13.8 mmHg for AML/OM 10/40 mg +
      hydrochlorothiazide 25 mg, and in non-Hispanics from -14.1/-7.8 mmHg to -25.4/
      13.7 mmHg (all p < 0.0001 versus baseline). A majority of patients achieved mean
      24 h, daytime, and nighttime ABP targets in both subgroups. Greater proportions
      of Hispanics achieved ABP targets versus non-Hispanics at week 12; however, this
      trend was reversed at week 20. Treatment was well tolerated. CONCLUSIONS:
      Switching to a fixed-dose combination of AML/OM +/- hydrochlorothiazide provided
      significant BP lowering and effectively controlled BP in a large proportion of
      Hispanic and non-Hispanic patients with hypertension uncontrolled on previous
      monotherapy.

PMID- 22855064
TI  - Gastrointestinal bleeding.

PMID- 22855065
TI  - Natural orifice transluminal endoscopic surgery.

PMID- 22855066
TI  - Endoscopic ultrasonography.

PMID- 22855067
TI  - Non-Barrett's esophageal and gastric tumors: diagnosis and treatment.

PMID- 22855068
TI  - Barrett's esophagus, reflux esophagitis, and eosinophilic esophagitis.

PMID- 22855069
TI  - Colon tumors and colonoscopy.

PMID- 22855070
TI  - Endoscopic retrograde cholangiopancreatography.

PMID- 22855071
TI  - Transsphenoidal surgery for microprolactinomas in women: results and prognosis.
AB  - BACKGROUND: Long-term dopamine agonist (DA) therapy is recommended as a first
      line approach for the management of microprolactinomas. However, DA therapy may
      be poorly tolerated by some patients, and therefore some patients continue to
      prefer surgery over DA therapy. AIM: The aim of our study was to evaluate factors
      associated with favorable outcomes after surgical treatment of microprolactinomas
      in women. METHODS: Thirty-two women (mean age 31.0 +/- 8.2 years) with confirmed
      microprolactinomas who were operated using transsphenoidal approach were included
      to the study. Twenty-two (61 %) women had previous DA therapy and ten (39 %)
      women preferred surgery as a first treatment. Mean follow-up was 4.2 +/- 2.7
      years. Surgery was considered to be effective and remission achieved if serum
      prolactin was normal without DA therapy and there were no signs of tumor re
      growth on neuroimaging. RESULTS: Nine (47.4 %) patients in whom remission was
      achieved did not receive preoperative DA therapy when compared to one (7.7 %)
      patient in whom remission was not achieved (p = 0.02). Remission after operation
      was achieved in nine out of ten (90 %) patients who did not receive DA therapy
      compared to ten out of 22 patients (45.5 %) who were treated with DAs (p = 0.01).
      The independent factor associated with good outcome following surgical treatment
      was no preoperative DA therapy (RR = 14.57 (1.43-148.1), p = 0.02). Surgical
      complications were permanent diabetes insipidus in two patients (6.3 %) and
      transient DI in five (15.6 %) patients. CONCLUSIONS: The main factor associated
      with favorable microprolactinoma surgery outcome in women was the absence of
      preoperative DA therapy.

PMID- 22855072
TI  - Crescent posterior fossa durotomy for occipito-marginal venous sinus
      preservation: a pilot study.
AB  - PURPOSE: The standard approach of midline suboccipital craniectomy entails
      sacrifice of the Occipito-marginal sinus. We have attempted to preserve this
      venous channel by using a durotomy technique which preserves this system. In a
      pilot study initiative, two groups of patients using this technique versus the
      standard approach, were compared in terms of per and post operative benefits,
      morbidity and complications. The literature with reference to the anatomy and
      venous flow dynamics of the occipital and marginal sinuses and their significance
      has been reviewed. Similarly, literature regarding dural closure technique with
      reference to postoperative complications has also been reviewed. METHODS: In this
      novel approach, the dura is opened as a crescent to avoid damage to the occipital
      sinus. This technique was compared with the standard midline dural opening
      technique by random usage of both techniques in 24 patients. RESULTS: The
      'crescent' approach has been found to reduce the need for duroplasty, with
      comfortable primary closure and to reduce the risk of postoperative
      pseudomeningocele. CONCLUSIONS: This is a novel dural opening technique which
      attempts to preserve the normal venous flow physiology. In essence it helps in
      increased primary dural closures and reduction of Pseudomeningiocele/CSF leak as
      well as blood loss and venous hypertension.

PMID- 22855074
TI  - Acute myocardial infarction without chest pain: a life-threatening variant?

PMID- 22855075
TI  - Management of delirium in critically ill older adults.
AB  - Delirium in older adults in critical care is associated with poor outcomes,
      including longer stays, higher costs, increased mortality, greater use of
      continuous sedation and physical restraints, increased unintended removal of
      catheters and self-extubation, functional decline, new institutionalization, and
      new onset of cognitive impairment. Diagnosing delirium is complicated because
      many critically ill older adults cannot communicate their needs effectively.
      Manifestations include reduced ability to focus attention, disorientation, memory
      impairment, and perceptual disturbances. Nurses often have primary responsibility
      for detecting and treating delirium, which can be extraordinarily complicated
      because patients are often voiceless, extremely ill, and require high levels of
      sedatives to facilitate mechanical ventilation. An aggressive, appropriate, and
      compassionate management strategy may reduce the suffering and adverse outcomes
      associated with delirium and improve relationships between nurses, patients, and
      patients' family members.

PMID- 22855076
TI  - Incidence and severity of phlebitis in patients receiving peripherally infused
      amiodarone.
AB  - BACKGROUND: Nurses noted that the rate of phlebitis was high when intravenous
      amiodarone was infused via a peripheral site. Hospital policy recommends a
      central vascular catheter, but this method is often not feasible because the drug
      is administered in emergent situations for short periods. OBJECTIVE: To determine
      the rate and severity of phlebitis in patients given peripherally infused
      amiodarone. METHODS: The literature, policy, and procedures for administration of
      amiodarone were reviewed; the pharmacy was consulted; and a data collection tool
      was developed. The tool was pilot tested and revised, and face validation was
      established. Data were collected during a 6-month period. A convenience sample
      was used. RESULTS: The study included a total of 12 patients. Each new infusion
      of intravenous amiodarone was considered a separate occurrence, for a total of 24
      infusions. Various grades of phlebitis developed in 8 patients (67%). Phlebitis
      developed at 12 of the 24 infusion sites (50%). CONCLUSIONS: Patients receiving
      peripherally infused amiodarone are at high risk for phlebitis. This complication
      may lead to infection, additional medical intervention, delay in treatment, and
      prolonged hospitalization.

PMID- 22855077
TI  - Use of a 1-piece chlorhexidine gluconate transparent dressing on critically ill
      patients.
AB  - BACKGROUND: New transparent dressings with chlorhexidine gluconate in the
      dressing are available. OBJECTIVES: To compare the effectiveness of a new 1-piece
      occlusive dressing that incorporates chlorhexidine gluconate with that of a
      dressing plus a chlorhexidine gluconate patch in maintaining the low rate of
      catheter-related bloodstream infections in the intensive care unit and to
      evaluate nurses' satisfaction with and cost of the new dressing. METHODS: A
      quality improvement observational study was done in an adult medical-surgical
      intensive care unit. All patients with a central venous catheter had initial
      and/or subsequent dressing changes done with the new dressing. The central
      catheter bundle elements of the Institute for Healthcare Improvement were
      followed. Patients were monitored for catheter-related bloodstream infections,
      and the rate of infection was calculated. RESULTS: During the study period of
      1881 device days, the infection rate was 0.051 per 1000 device days, compared
      with a rate of 0.052 in 2008. Nurses preferred the new dressing. Cost savings
      were $3807. CONCLUSION: A low rate of catheter-related bloodstream infections can
      be maintained, nurses' satisfaction achieved, and cost savings realized with the
      new dressing.

PMID- 22855078
TI  - Using evidence-based practice to prevent ventilator-associated pneumonia.
AB  - BACKGROUND: Strategies are needed to help prevent ventilator-associated
      pneumonia. OBJECTIVE: To develop a ventilator bundle and care practices for
      nurses in critical care units to reduce the rate of ventilator-associated
      pneumonia. METHOD: The ventilator bundle developed by the Institute for
      Healthcare Improvement was expanded to include protocols for mouth care and hand
      washing, head-of-bed alarms, subglottic suctioning, and use of an electronic
      compliance feedback tool. Compliance audits were used to provide immediate
      electronic feedback. RESULTS: Adherence to practices included in the bundle
      increased. Compliance rates were greater than 98% for prophylaxis for peptic
      ulcer disease and deep-vein thrombosis, interruption of sedation, and elevation
      of the head of the bed. The compliance rate for the oral care protocol increased
      from 76% to 96.8%. Readiness for extubation reached at least 92.4%. Rates of
      ventilator-associated pneumonia decreased from 9.47 to 1.9 cases per 1000
      ventilator days. The decrease in rates produced an estimated savings of
      approximately $1.5 million. CONCLUSION: Strict adherence to bundled practices for
      preventing ventilator-associated pneumonia, enhanced accountability for
      initiating protocols, use of a feedback system, and interdisciplinary
      collaboration improved patients' outcomes and produced marked savings in costs.

PMID- 22855079
TI  - Drug reaction, skin care, skin loss.
AB  - Stevens-Johnson syndrome is a rare, potentially fatal drug reaction that causes
      necrosis of epidermal cells. Early recognition of the syndrome is essential to
      prevent complications. This article discusses identification, complications, and
      treatment of Stevens-Johnson syndrome.

PMID- 22855081
TI  - Removal of a pulmonary artery catheter in the presence of implanted leads.

PMID- 22855080
TI  - Medical devices and patient safety.
AB  - Errors related to health care devices are not well understood. Nurses in
      intensive care and progressive care environments can benefit from understanding
      manufacturer-related error and device-use error, the principles of human factors
      engineering, and the steps that can be taken to reduce risk of errors related to
      health care devices.

PMID- 22855083
TI  - Family presence: visitation in the adult ICU.

PMID- 22855082
TI  - An enteral nutrition protocol to improve efficiency in achieving nutritional
      goals.

PMID- 22855084
TI  - I am a critical care nurse.

PMID- 22855085
TI  - Case histories in the education of advanced practice nurses.
AB  - Case histories--rich, anecdotal narratives--are theorized to support the
      acquisition of cognitive, social, cultural, and emotional knowledge and motor
      skills through active learning. This manuscript focuses on the value of case
      histories in teaching and evaluating acute and critical care advanced practice
      nursing students. Information about the use of case histories in advanced
      critical care education and clinical practice is limited. Case histories support
      student-centered learning and development of clinical reasoning. An exemplar of a
      case history is provided, and application of case histories to both electronic
      and classroom settings is explored.

PMID- 22855086
TI  - Spontaneous coronary artery dissection: a rare threat to young women.
AB  - Spontaneous coronary artery dissection not associated with underlying coronary
      artery disease is rare. When the dissection does occur, it most often is
      manifested as an acute ST-elevation myocardial infarction in young women.
      Although the condition can occur in men, most often it involves women who are in
      their third trimester of pregnancy or the early postpartum period or are engaging
      in vigorous exercise. Because little is known about spontaneous coronary artery
      dissection in this population of women, recommendations for treatment are the
      same as for treatment of acute myocardial infarction associated with
      atherosclerotic coronary disease.

PMID- 22855093
TI  - Lentiviral-mediated administration of IL-25 in the CNS induces alternative
      activation of microglia.
AB  - Interleukin-25 (IL-25) is the only anti-inflammatory cytokine of the IL-17
      family, and it has been shown to be efficacious in inhibiting neuroinflammation.
      Known for its effects on cells of the adaptive immune system, it has been more
      recently described to be effective also on cells of the innate immune system,
      namely macrophages. We used a lentiviral-mediated gene therapy approach to
      deliver IL-25 to the central nervous system (CNS) in two mouse models of
      neuroinflammation, entorhinal cortex lesion and experimental autoimmune
      encephalomyelitis. In both, we found that IL-25 gene therapy was able to modulate
      CNS myeloid cells, either infiltrating macrophages or resident microglia, towards
      an anti-inflammatory, tissue-protective phenotype, as testified by the increase
      in markers such as Arginase-1 (Arg1), Mannose receptor 1 (CD206) and Chitinase 3
      like 3 (Ym1). As a consequence, neuroinflammation was partly inhibited and the
      CNS protected from immune-mediated damage. To our knowledge, this is the first
      example of M2 shift (alternative activation) induced in vivo on CNS-resident
      myeloid cells by gene therapy, and may constitute a promising strategy to
      investigate the potential role of protective microglia in neurological disorders.

PMID- 22855092
TI  - Heparin-binding correlates with increased efficiency of AAV1- and AAV6-mediated
      transduction of striated muscle, but negatively impacts CNS transduction.
AB  - Gene delivery vectors derived from adeno-associated virus (AAV) have great
      potential as therapeutic agents. rAAV1 and rAAV6, efficiently target striated
      muscle, but the mechanisms that determine their tropism remain unclear. It is
      known that AAV6, but not AAV1, interacts with heparin-sulfate proteoglycans
      (HSPG). HSPGs are not primary receptors for AAV6, but heparin interactions may
      affect tissue tropism and transduction. To investigate these possibilities, we
      generated rAAV1 and rAAV6 capsids that do or do not bind heparin. We evaluated
      the transduction profile of these vectors in vivo across multiple routes of
      administration, and found that heparin-binding capability influences tissue
      transduction in striated muscle and neuronal tissues. Heparin-binding capsids
      transduce striated muscle more efficiently than non-binding capsids, via both
      intramuscular and intravenous injection. However, rAAV6 achieved greater muscle
      transduction than the heparin-binding rAAV1 variant, suggesting that there are
      additional factors that influence differences in transduction efficiency between
      AAV1 and AAV6. Interestingly, the opposite trend was found when vectors were
      delivered via intracranial injection. Non-binding vectors achieved robust and
      widespread gene expression, whereas transduction via heparin-binding serotypes
      was substantially reduced. These data indicate that heparin-binding capability is
      an important determinant of transduction that should be considered in the design
      of rAAV-mediated gene therapies.

PMID- 22855094
TI  - Education becomes focus of classwide opioid REMS.

PMID- 22855095
TI  - New FDA law will help preserve production of "life-saving" drugs.

PMID- 22855096
TI  - Pharmacy projects selected for Innovation Center awards.

PMID- 22855097
TI  - Illinois hospital, specialty pharmacy team up to improve patient care.

PMID- 22855098
TI  - Collaborating on a residency research project.

PMID- 22855099
TI  - Posted versus actual drug shortages.

PMID- 22855100
TI  - Posted versus actual drug shortages.

PMID- 22855101
TI  - Optimizing 340B purchasing practices.

PMID- 22855102
TI  - Translating health care imperatives and evidence into practice: the "Institute of
      Pharmacy" report.

PMID- 22855103
TI  - Exemestane for primary prevention of breast cancer in postmenopausal women.
AB  - PURPOSE: The benefits and risks of exemestane for the primary prevention of
      breast cancer are discussed and compared with other breast cancer chemoprevention
      therapies. SUMMARY: Selective estrogen-receptor modulators (SERMs) are the
      current mainstay for primary prevention of breast cancer. As an alternative,
      exemestane, an aromatase inhibitor, has been evaluated for breast cancer
      prevention in postmenopausal women. A study of 4560 high-risk postmenopausal
      women taking exemestane 25 mg daily for a median of three years found a 65%
      relative reduction in the annual occurrence of invasive breast cancer compared
      with placebo (0.19% versus 0.55%; hazard ratio, 0.35; 95% confidence interval
      [CI], 0.18-0.70; p = 0.002) and a 53% reduction in invasive plus noninvasive
      breast cancer (0.35% versus 0.77%; hazard ratio, 0.47; 95% CI, 0.27-0.79; p =
      0.04). Adverse effects from exemestane are generally mild, with the most common
      being diarrhea, joint pain, and menopausal-related symptoms. Importantly,
      exemestane did not increase the risks of endometrial cancers, thromboembolism,
      cardiovascular events, or cataracts. However, joint stiffness and arthralgia were
      more common when compared with tamoxifen or raloxifene. Ongoing clinical trials
      with other aromatase inhibitors are underway to evaluate the benefits and long
      term skeletal risks. CONCLUSION: Exemestane 25 mg daily taken for at least three
      years is a new option for the prevention of breast cancer in high-risk
      postmenopausal women. Indirectly compared with SERMs, exemestane has a similar
      frequency of bothersome adverse effects without the risk of thromboembolic events
      or endometrial cancer, though an increased risk of osteoporosis is of concern.

PMID- 22855104
TI  - A new epoprostenol formulation for the treatment of pulmonary arterial
      hypertension.
AB  - PURPOSE: The pharmacology and pharmacokinetics of a novel formulation of
      epoprostenol for the treatment of pulmonary arterial hypertension (PAH) are
      reviewed, with guidance on addressing a number of important safety
      considerations. SUMMARY: Epoprostenol is a direct vasodilator of the pulmonary
      and systemic vasculature indicated for improving exercise capacity in patients
      with PAH. Veletri, a recently approved formulation of epoprostenol for continuous
      i.v. infusion, offers increased stability relative to other available
      epoprostenol products. Therefore, the use of Veletri can lessen the therapy
      burden associated with the other available formulation of the drug by allowing
      for the advance preparation of infusion pump cassettes (at certain
      concentrations) and administration at room temperature without the need for
      cooling with ice packs. Sterility, however, is of concern with outpatient
      preparation of epoprostenol-containing cassettes stored for the maximum duration
      according to stability guidelines. All epoprostenol infusions are classified as
      high-risk therapies due to complex dosing, the drug's short half-life, and the
      potential for life-threatening rebound PAH with abrupt discontinuation. Adverse
      effects reported in >=10% of participants in clinical trials of Veletri included
      flushing (58%), headache (49%), nausea or vomiting (32%), hypotension (16%),
      chest pain (11%), and anxiety, nervousness, or agitation (11%). As with other
      epoprostenol formulations, the use of Veletri requires an evaluation of health
      system medication-use practices to ensure patient safety. CONCLUSION: Veletri
      provides an epoprostenol therapy option that reduces some of the inconveniences
      of the other formulation. Drug stability is dependent on cassette concentrations,
      which may be limited by sterility concerns with outpatient preparation. Use of
      this new agent within the health system requires an evaluation of practices to
      ensure patient safety.

PMID- 22855105
TI  - Cardiac arrest and possible seizure activity after vincristine injection.
AB  - PURPOSE: A case of cardiac arrest and possible seizure activity after vincristine
      injection in a child is reported. SUMMARY: A two-year-old African-American girl
      with stage IV hepatoblastoma arrived at a clinic to receive her fourth dose of
      vincristine as part of standard induction therapy. The patient had tolerated her
      first three doses of vincristine sulfate 0.7 mg (1.5 mg/m(2)) i.v. without any
      adverse events. Laboratory tests, including a comprehensive metabolic panel,
      conducted before chemotherapy administration were unremarkable. Shortly after the
      administration of vincristine, the patient experienced tonic extension of all
      four extremities and upward sustained deviation of the eyes. The patient then
      became limp and exhibited perioral cyanosis. Further evaluation revealed a lack
      of central pulses and a heartbeat. Cardiopulmonary resuscitation was begun with
      chest compressions and positive-pressure ventilation via a bag-mask device. After
      approximately 45 seconds, her pulses returned, and perioral cyanosis resolved.
      She was admitted to the pediatric intensive care unit for further evaluation. Her
      serum electrolyte, glucose, and ammonia concentrations were within normal limits.
      No yeast or bacteria were isolated from the patient's blood. No contributing
      cardiac or neurologic factors were identified. The patient recovered without
      sequelae and was discharged after 72 hours. Subsequent doses of vincristine were
      administered with no adverse events, and the patient successfully completed her
      treatment regimen. CONCLUSION: A two-year-old girl with hepatoblastoma had
      seizurelike activity and cardiac arrest shortly after receiving i.v. vincristine.
      She received multiple doses of the drug before and after this event without a
      similar reaction. No contributing factors for the one-time event were identified.

PMID- 22855106
TI  - Method to determine allocation of clinical pharmacist resources.
AB  - PURPOSE: An objective methodology to guide decisions by hospital pharmacy
      departments on the best use of clinical pharmacist personnel is described.
      SUMMARY: To help determine the optimal deployment of state-licensed Clinical
      Pharmacist Specialist (CPS) staff, a task force led by the pharmacy department at
      University of North Carolina (UNC) Hospitals developed an objective approach to
      evaluating the relative need for and potential impact of CPS expertise within the
      medical center's many service units. After analyzing several years of patient
      census and medication-use data and using information from proprietary databases
      (Thomson Reuters) to calculate a "service-specific pharmacy intensity score" for
      each hospital service, the task force identified five staff-allocation metrics
      best suited to the medical center's service-based pharmacy coverage model. By
      applying the methodology, it was determined that CPS expertise was most needed in
      the UNC Hospitals adult medicine oncology service, the bone marrow transplant
      service, and the medical and neonatal intensive care units. The tool was
      initially used to validate the pharmacy department's existing human resource
      allocation and has since been used to guide budgeting for and deployment of newly
      added CPS positions. CONCLUSION: A novel tool to guide the application of
      pharmacy human resources incorporates the objective criteria of patient census,
      patient acuity, teaching involvement, drug expenditures, and use of high-risk
      medications. The tool can be used to determine the appropriate allocation and
      placement of clinical pharmacist resources in a service-based coverage model.

PMID- 22855107
TI  - Compatibility and stability of telavancin and vancomycin in heparin or sodium
      citrate lock solutions.
AB  - PURPOSE: The compatibility and stability of telavancin and vancomycin in heparin
      or sodium citrate lock solutions were evaluated. METHODS: Telavancin and
      vancomycin hydrochloride injection powder lyophilized for solution were
      reconstituted with 0.9% sodium chloride injection at room temperature according
      to the manufacturer's instructions and then further diluted with (1) commercially
      available heparin sodium to reach a final heparin concentration of 2500 units/mL
      or (2) sodium citrate solution 2.2% or 4% to achieve final telavancin and
      vancomycin concentrations of 2 and 5 mg/mL. Physical stability, chemical
      compatibility, and biological anticoagulant stability were analyzed for each
      antibiotic-anticoagulant combination immediately after preparation and at 24, 48,
      and 72 hours. Changes in coagulation were measured at each time point and
      compared using two-way analysis of variance. RESULTS: Both telavancin and
      vancomycin retained at least 90% of the initial concentration after incubation at
      37  degrees C over 72 hours. The biological stability of vancomycin 2 mg/mL and
      telavancin 2 mg/mL did not significantly alter prothrombin time when compared
      with that of 0.9% sodium chloride injection. However, telavancin 5 mg/mL and
      vancomycin 5 mg/mL significantly increased the activated partial thromboplastin
      time at 72 hours compared with the control solution. Visual precipitation only
      occurred with vancomycin-containing solutions; however, this dissipated after 10
      minutes. CONCLUSION: Telavancin 2 and 5 mg/mL was physically compatible in
      combination with heparin 2500 units/mL and with sodium citrate 2.2% and 4% over
      72 hours. Vancomycin 2 and 5 mg/mL initially precipitated in the sodium citrate
      2.2% formulation, but no precipitation was noted after 10 minutes of incubation
      at 37  degrees C. Telavancin and vancomycin 2 and 5 mg/mL retained over 90% of
      the initial concentration after incubation at 37  degrees C over 72 hours.

PMID- 22855108
TI  - Survey of learning opportunities in academia for pharmacy residents.
AB  - PURPOSE: The types of teaching experiences offered in academia in pharmacy
      residency programs affiliated with or offered through colleges of pharmacy
      throughout the United States were evaluated. METHODS: Two 15-item questionnaires
      were developed, one for programs that offer a concentrated rotation in academia
      and one for programs that offer longitudinal opportunities in academia. These
      questionnaires were developed to assess the activities incorporated into the
      different learning experiences, the number of residents completing concentrated
      rotations, the residency director's perception of the benefit to the residents,
      and barriers that exist for institutions that do not offer concentrated
      rotations. The questionnaires were distributed electronically to pharmacy
      residency directors at academic medical centers and colleges of pharmacy in the
      University HealthSystem Consortium listserver. The responses were analyzed with
      descriptive statistics. RESULTS: Of the 154 institutions identified for survey
      distribution, 86 were academic medical centers and 68 were colleges of pharmacy
      and affiliated programs. Program directors from 99 institutions completed a
      questionnaire (response rate, 64.3%), representing 434 postgraduate year 1 (PGY1)
      and 290 postgraduate year 2 (PGY2) residency positions. Thirty-six percent (n =
      36) of respondents offered a concentrated rotation in academia, and 64% (n = 63)
      offered longitudinal opportunities in academia. Sixty-six institutions offered a
      teaching certificate program; however, it was mandatory in only 42% of programs.
      CONCLUSION: The majority of PGY1 and PGY2 residency programs surveyed did not
      offer concentrated rotations in academia but did offer longitudinal opportunities
      for residents to gain teaching experience. The majority of programs that did not
      offer these experiences did want formal training on how to provide these
      opportunities.

PMID- 22855109
TI  - Successful importation of cytarabine into the United States during a critical
      national drug shortage.
AB  - PURPOSE: The importation of cytarabine into the United States during a critical
      national drug shortage is described. SUMMARY: In March 2011, the hospital
      pharmacy team at an acute care hospital was struggling to supply cytarabine for
      four specific patients, all of whom needed critical maintenance therapy after
      induction. Cytarabine was not available from any source in the United States, and
      the team had no realistic projected release dates for back orders. Idis UK, a
      pharmaceutical distributor, was asked to identify available drug and eventually
      found an unrestricted source of cytarabine in Switzerland. Once available drug
      was identified, a price quote for the supply amount was written for our
      consideration. This was inspected carefully to ensure that the drug, strength,
      dosage form, and any other ingredients listed were indeed what were expected. The
      pharmacy department worked with the hospital's department of finance and
      accounting to submit the necessary financial paperwork. Payment was
      electronically sent to the distributor before the drug was shipped. Before the
      order for cytarabine was placed, the associated risks and benefits were assessed.
      The patients provided consent to treatment with the unapproved product.
      Acceptance of the price quote and instructions to order the drug were e-mailed to
      the distributor. The necessary documentation was completed and included with the
      shipment. The importation process, from initial inquiries to delivery, took 21
      days. CONCLUSION: The importation of cytarabine amid a drug shortage required a
      complex process that involved the efforts of an overseas distributor, the
      cooperation of multiple health professionals, and meticulous attention to detail.

PMID- 22855110
TI  - Effect of closed-loop order processing on the time to initial antimicrobial
      therapy.
AB  - PURPOSE: The results of a study comparing the average time to initiation of i.v.
      antimicrobial therapy with closed-versus open-loop order entry and processing are
      reported. METHODS: A retrospective cohort study was performed to compare order-to
      administration times for initial doses of i.v. antimicrobials before and after a
      closed-loop order-processing system including computerized prescriber order entry
      (CPOE) was implemented at a large medical center. A total of 741 i.v.
      antimicrobial administrations to adult patients during designated five-month
      preimplementation and postimplementation study periods were assessed. Drug-use
      reports generated by the pharmacy database were used to identify order-entry
      times, and medication administration records were reviewed to determine times of
      i.v. antimicrobial administration. RESULTS: The mean +/- S.D. order-to
      administration times before and after the implementation of the CPOE system and
      closed-loop order processing were 3.18 +/- 2.60 and 2.00 +/- 1.89 hours,
      respectively, a reduction of 1.18 hours (p < 0.0001). Closed-loop order
      processing was associated with significant reductions in the average time to
      initiation of i.v. therapy in all patient care areas evaluated (cardiology,
      general medicine, and oncology). The study results suggest that CPOE-based closed
      loop order processing can play an important role in achieving compliance with
      current practice guidelines calling for increased efforts to ensure the prompt
      initiation of i.v. antimicrobials for severe infections (e.g., sepsis,
      meningitis). CONCLUSION: Implementation of a closed-loop order-processing system
      resulted in a significant decrease in order-to-administration times for i.v.
      antimicrobial therapy.

PMID- 22855112
TI  - Attentional control and competition between episodic representations.
AB  - The relationship between attentional control and episodic representation was
      investigated in six experiments that employed a variant of the classic
      attentional blink paradigm. We introduced a task-irrelevant (unpredictive) color
      match between the first and second target stimulus in a three-stream rapid serial
      visual presentation task. When this match was present, the first target reliably
      elicited a priming benefit to the identification of the second, lateralized
      target. However, this was only the case when the identities of the targets did
      not belong to the same category (digits, letters, or symbols). When targets did
      belong to the same category, interference was observed instead of priming,
      particularly at Lag 1. Furthermore, when color was the target-defining feature,
      interference at Lag 1 gave way to priming at longer lags. The interference effect
      is attributed to partial overlap between competing episodic target
      representations, which affects the availability of their overlapping features for
      successive attentional selection in rapid serial visual presentation.

PMID- 22855113
TI  - Comparison of diary-derived bladder and sleep measurements across OAB
      individuals, primary insomniacs, and healthy controls.
AB  - INTRODUCTION AND HYPOTHESIS: Can diary-derived bladder and sleep measurements
      differentiate individuals with overactive bladder syndrome (OAB) from individuals
      with primary insomnia and healthy controls? METHODS: Bladder- and sleep-diary
      data were compared in nine OAB, ten insomnia, and five control individuals. One
      way analysis of variance (ANOVA) was used for normally and Kruskal-Wallis test
      for nonnormally distributed variables, followed, when significant effects were
      found, by pairwise comparisons. RESULTS: OAB individuals woke up as frequently as
      insomniacs, but their awakenings were respectively shorter in duration (18.6 vs.
      38.1 min.) and were predominantly initiated by nocturic events (89.2 vs. 23.9 %
      respectively). Regardless, their reported quality of sleep was as impaired as for
      the insomniacs. Furthermore, smaller mean volume voided awakenings were evident
      not only in those with OAB but also in insomniacs compared to controls.
      CONCLUSIONS: Bladder- and sleep-diary data provide means to differentiate those
      with OAB from those with insomnia and healthy controls. Awakenings in OAB
      individuals were shorter than those with insomnia and much more likely due to the
      need to void. Thus, a reduction in the number of nocturic voids could be the most
      appropriate sleep-related outcome for nocturia therapy in individuals with OAB.
      In addition, limited nocturnal bladder capacity, though expected in OAB, was
      unexpectedly found in insomnia, possibly reflecting the role of consciousness
      (wakefulness at night) in modulating bladder sensation.

PMID- 22855115
TI  - Urogynecology digest : Presented by Andrea Crane.

PMID- 22855114
TI  - Urethral sphincter innervation and clitoral blood flow after the transobturator
      (TOT) approach.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to exclude neurovascular
      damage due to prosthetic mini-invasive surgery using transobturator tape (TOT) by
      pre- and postoperative electromyography (EMG) of the striated urethral sphincter
      and a color Doppler ultrasonography evaluation of clitoral blood flow. METHODS: A
      total of 25 women affected by clinical stress urinary incontinence (SUI) were
      enrolled. After undergoing urodynamic assessment, pelvic organ prolapse
      quantification, urine culture, Q-tip test, and stress test, each subject
      underwent color Doppler ultrasonography to record clitoral blood flow and EMG of
      the urethral sphincter with a needle electrode inserted through the mucosa into
      the muscle tissue before surgery. A single urogynecologist performed the TOT
      surgical technique for the treatment of all patients. Urogynecologic examination,
      EMG, and color Doppler ultrasound follow-up were performed at 1 and 6 months
      after surgery. RESULTS: At the urogynecologic examination performed 1 and 6
      months after the TOT approach the stress test was negative, urethral
      hypermobility was reduced, and sling exposure was not observed for each patient.
      There was no statistically significant difference in electromyographic values (p
      > 0.05) in both the follow-ups with regard to baseline values. Pulsatility index
      (PI), resistance index (RI), and peak systolic velocity (PSV) values increased
      during the first follow-up (p < 0.01); PI and RI values increased during the
      second follow-up with respect to baseline values (p < 0.01) CONCLUSIONS: TOT
      prosthesis surgery, avoiding denervation and devascularization of pelvic
      structures, does not damage the urethral sphincter.

PMID- 22855116
TI  - Genitourinary symptoms in patients with adenomyosis.
AB  - INTRODUCTION AND HYPOTHESIS: Adenomyosis causes problems in women, including
      dysmenorrhea and abnormally heavy and prolonged menstrual bleeding; however, its
      etiology is unknown. We hypothesized that urinary symptoms are frequent in
      patients with adenomyosis and that they affect the patients' quality of life.
      METHODS: We conducted a pilot study from September 2011 to December 2011. Ninety
      one patients with an ultrasound diagnosis of uterine adenomyosis comprised the
      study group (adenomyosis group). Ninety-four women with a normal-appearing
      uterine myometrium on ultrasound comprised the control group. Patients filled out
      two validated questionnaires, the Urogenital Distress Inventory (UDI-6) and the
      Incontinence Impact Questionnaire (IIQ-7). Patients also underwent a pelvic
      examination and urinary symptoms were recorded. Groups were compared using the
      nonparametric Mann-Whitney U test, chi-square test, and Fisher's exact test.
      RESULTS: The frequency of urinary symptoms was significantly higher in the
      adenomyosis group than in the control group (P = 0.0001), including stress
      urinary incontinence, urgency, daytime frequency, urge urinary incontinence, and
      dyspareunia. Total UDI scores were significantly higher in the adenomyosis group
      than those in the control group (P < 0.0001), as were IIQ scores of questions
      regarding social relations (P < 0.05). CONCLUSIONS: Our results suggest that
      urinary tract dysfunction is associated with adenomyosis and that urinary
      symptoms may affect patients' quality of life.

PMID- 22855117
TI  - The effects of a valgus collapse knee position on in vivo ACL elongation.
AB  - There are conflicting data regarding what motions increase ACL injury risk. More
      specifically, the mechanical role of valgus collapse positions during ACL injury
      remains controversial. Our objective was to evaluate ACL elongation in a model
      that mimics knee movements thought to occur during ACL injury. Eight healthy male
      subjects were imaged using MR and biplanar fluoroscopy to measure the in vivo
      elongation of the ACL and its functional bundles during three static knee
      positions: full extension, 30 degrees  of flexion, and a position intended to
      mimic a valgus collapse position described in the literature. For this study, the
      valgus collapse position consisted of 30 degrees  of knee flexion, internal
      rotation of the hip, and 10 degrees  of external tibial rotation. ACL length
      decreased significantly from full extension (30.2 +/- 2.6 mm) to 30 degrees  of
      flexion (27.1 +/- 2.2 mm). ACL length further decreased in the valgus collapse
      position (25.6 +/- 2.4 mm). Both functional bundles of the ACL followed similar
      trends with regards to decreases in length in each of the three positions. Since
      strain would follow patterns of ACL length, landing on an extended knee may be a
      more relevant risk factor for ACL injuries than the valgus collapse position in
      males. Future studies should evaluate the effects of dynamic motion patterns on
      in vivo ACL strains.

PMID- 22855118
TI  - Cationic nanoparticles have superior transvascular flux into solid tumors:
      insights from a mathematical model.
AB  - Despite their great promise, only a few nanoparticle formulations have been
      approved for clinical use in oncology. The failure of nano-scale drugs to enhance
      cancer therapy is in large part due to inefficient delivery. To overcome this
      outstanding problem, a better understanding of how the physical properties (i.e.,
      size, surface chemistry, and shape) of nanoparticles affect their transvascular
      transport in tumors is required. In this study, we developed a mathematical model
      for nanoparticle delivery to solid tumors taking into account electrostatic
      interactions between the particles and the negatively-charged pores of the vessel
      wall. The model predictions suggest that electrostatic repulsion has a minor
      effect on the transvascular transport of nanoparticles. On the contrary,
      electrostatic attraction, caused even by small cationic charges (surface charge
      density less than 3 * 10(-3) C/m(2)) can lead to a twofold or more increase in
      the transvascular flux of nanoparticles into the tumor interstitial space.
      Importantly, for every nanoparticle size, there is a value of charge density
      above which a steep increase in transvascular transport is predicted. Our model
      provides important guidelines for the optimal design of nanoparticle formulation
      for delivery to solid tumors.

PMID- 22855120
TI  - Optimizing magnetic nanoparticle based thermal therapies within the physical
      limits of heating.
AB  - Magnetic nanoparticle (mNP) based thermal therapies have demonstrated relevance
      in the clinic, but effective application requires an understanding of both its
      strengths and limitations. This study explores two critical limitations for
      clinical use: (1) maximizing localized mNP heating, while avoiding bulk heating
      due to inductive coupling of the applied field with the body and (2) the limits
      of treatable volumes, related to basic heat transfer. Two commercially available
      mNPs are investigated, one superparamagnetic and one ferromagnetic, thereby
      allowing a comparison between the two fundamental types of mNPs (both of which
      are being evaluated for clinical use). Important results indicate that in
      dispersed solutions, the superparamagnetic mNPs outperform on a per mass basis
      (2* better), but the ferromagnetic mNPs outperform on a per nanoparticle basis
      (170* better), at the fields of highest clinical relevance (approximately 100 kHz
      and 20 kA/m). We also demonstrate a new method of observing heating in microliter
      droplets of mNP solution, leading to scaling analyses that suggest treatable
      tumor volumes should be >=2 mm in diameter (for mNP loading of >=10 mg Fe/g
      tumor), to achieve therapeutic temperatures >=43  degrees C. This technique also
      provides a novel platform for quantifying heating from microgram quantities of
      mNPs.

PMID- 22855119
TI  - Design and testing of a percutaneously implantable fetal pacemaker.
AB  - We are developing a cardiac pacemaker with a small, cylindrical shape that
      permits percutaneous implantation into a fetus to treat complete heart block and
      consequent hydrops fetalis, which can otherwise be fatal. The device uses off-the
      shelf components including a rechargeable lithium cell and a highly efficient
      relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made
      from activated iridium can be screwed into the myocardium, followed by release of
      the pacemaker and a short, flexible lead entirely within the chest of the fetus
      to avoid dislodgement from fetal movement. Acute tests in adult rabbits
      demonstrated the range of electrical parameters required for successful pacing
      and the feasibility of successfully implanting the device percutaneously under
      ultrasonic imaging guidance. The lithium cell can be recharged inductively as
      needed, as indicated by a small decline in the pulsing rate.

PMID- 22855121
TI  - Microfluidic system for facilitated quantification of nanoparticle accumulation
      to cells under laminar flow.
AB  - The identification of novel, synthetic targeting ligands to endothelial receptors
      has led to the rapid development of targeted nanoparticles for drug, gene and
      imaging probe delivery. Central to development and optimization are effective
      models for assessing particle binding in vitro. Here, we developed a simple and
      cost effective method to quantitatively assess nanoparticle accumulation under
      physiologically-relevant laminar flow. We designed reversibly vacuum-sealed PDMS
      microfluidic chambers compatible with 35 mm petri dishes, which deliver uniform
      or gradient shear stress. These chambers have sufficient surface area for facile
      cell collection for particle accumulation quantitation through FACS. We tested
      this model by synthesizing and flowing liposomes coated with APN (K (D) ~ 300
      MUM) and VCAM-1-targeting (K (D) ~ 30 MUM) peptides over HUVEC. Particle binding
      significantly increased with ligand concentration (up to 6 mol%) and decreased
      with excess PEG. While the accumulation of particles with the lower affinity
      ligand decreased with shear, accumulation of those with the higher affinity
      ligand was highest in a low shear environment (2.4 dyne/cm(2)), as compared with
      greater shear or the absence of shear. We describe here a robust flow chamber
      model that is applied to optimize the properties of 100 nm liposomes targeted to
      inflamed endothelium.

PMID- 22855122
TI  - Dirty hands: photodynamic killing of human pathogens like EHEC, MRSA and Candida
      within seconds.
AB  - Hand hygiene is one of the most important interventions for reducing transmission
      of nosocomial life-threatening microorganisms, like methicillin resistant
      Staphylococcus aureus (MRSA), enterohemorrhagic Escherichia coli (EHEC) or
      Candida albicans. All three pathogens have become a leading cause of infections
      in hospitals. Especially EHEC is causing severe diarrhoea and, in a small
      percentage of cases, haemolytic-uremic syndrome (HUS) as reported for E. coli
      104:H4 in Germany 2011. We revealed the possibility to inactivate very fast and
      efficiently MRSA, EHEC and C. albicans using the photodynamic approach. MRSA,
      EHEC and C. albicans were incubated in vitro with different concentrations of
      TMPyP for 10 s and illuminated with visible light (50 mW cm(-2)) for 10 and 60 s.
      1 MUmol l(-1) of TMPyP and an applied radiant exposure of 0.5 J cm(-2) achieved a
      photodynamic killing of >=99.9% of MRSA and EHEC. Incubation with higher
      concentrations (up to 100 MUmol l(-1)) of TMPyP caused bacteria killing of >5
      log(10) (>=99.999%) after illumination. Efficient Candida killing (>=99.999%) was
      achieved first at a higher light dose of 12 J cm(-2). Different rise and decay
      times of singlet oxygen luminescence signals could be detected in Candida cell
      suspensions for the first time, indicating different oxygen concentrations in the
      surrounding for the photosensitizer and singlet oxygen, respectively. This
      confirms that TMPyP is not only found in the water-dominated cell surrounding,
      but also within the C. albicans cells. Applying a water-ethanol solution of TMPyP
      on ex vivo porcine skin, fluorescence microscopy of histology showed that the
      photosensitizer was exclusively localized in the stratum corneum regardless of
      the incubation time. TMPyP exhibited a fast and very effective killing rate of
      life-threatening pathogens within a couple of seconds that encourages further
      testing in an in vivo setting. Being fast and effective, antimicrobial
      photodynamic applications might become acceptable as a tool for hand hygiene
      procedures and also in other skin areas.

PMID- 22855123
TI  - Perioperative management for parturients with pulmonary hypertension: experience
      with 30 consecutive cases.
AB  - Pregnancy with pulmonary hypertension is considered to be associated with
      increased maternal and neonatal mortality. We retrospectively reviewed all
      parturients with pulmonary hypertension who registered at our hospital between
      1999 and December 2008. We collected information about patient characteristics,
      including maternal age, gravida and para, pulmonary hypertension category, New
      York Heart Association (NYHA) functional class, pulmonary artery pressure, mode
      of delivery and type of anesthesia, use of anticoagulation and advanced therapy
      (nitric oxide, prostacyclin analogus, bosentan or sildenafil). The overall
      maternal mortality was 16.7% in puerperium, and there were four fetal/neonatal
      deaths (13%). Logistic regression could not identify any factors, including modes
      of anesthesia, mode of delivery, and categories and severity of pulmonary
      hypertension, that were significant predictors of mortality. Maternal mortality
      in parturients with pulmonary hypertension is high and women with pulmonary
      hypertension who become pregnant warrant a multidisciplinary approach.

PMID- 22855124
TI  - Engineering the surface properties of microfluidic stickers.
AB  - We introduce a simple and effective method to tailor the wetting and adhesion
      properties of thiolene-based microfluidic devices. This one-step lithographic
      scheme combines most of the advantages offered by the current methods employed to
      pattern microchannels: (i) the channel walls can be modified in situ or ex situ,
      (ii) their wettability can be varied in a continuous manner, (iii) heterogeneous
      patterning can be easily accomplished, with contact-angle contrasts extending
      from 0 to 90 degrees  for pure water, (iv) the surface modification has proven to
      be highly stable upon aging and heating. We first characterize the wetting
      properties of the modified surfaces. We then provide the details of two
      complementary methods to achieve surface patterning. Finally, we demonstrate the
      two methods with three examples of applications: the capillary guiding of fluids,
      the production of double emulsions, and the culture of cells on adhesive
      micropatterns.

PMID- 22855125
TI  - Simple and rapid detection of swine hepatitis E virus by reverse transcription
      loop-mediated isothermal amplification.
AB  - Hepatitis E virus (HEV) is an enteric pathogen of humans and animals, and pigs
      have been considered an important reservoir of this virus. Recent evidence has
      indicated the cross-species transmission of hepatitis E virus (HEV) from pigs to
      humans, causing zoonosis, mostly via consumption of uncooked or undercooked
      animal meat/viscera. In this study, we have developed a one-step RT-LAMP assay
      for rapid detection of swine HEV. Specific primer sets targeting the ORF3 gene
      were designed. The sensitivity of the RT-LAMP assay was 10(1) copies/MUl of RNA
      template, which was tenfold higher than that of RT-nPCR. The specificity of this
      assay was demonstrated by the lack of amplification of DNA/RNA from other swine
      viruses. Furthermore, a total of 41 bile samples were subjected to RT-LAMP and RT
      nPCR. Eighteen positive samples were detected by RT-nPCR, while 36 positive
      samples were detected by RT-LAMP, indicating that the sensitivity of the RT-LAMP
      assay was higher than that of the conventional RT-nPCR assay. The RT-LAMP assay
      reported here may be used for diagnosis of swine HEV, not only in laboratories
      but also under field conditions.

PMID- 22855126
TI  - The population genetics of maize dwarf mosaic virus in Spain.
AB  - The population genetics of maize dwarf mosaic virus (MDMV) in Spain was assessed
      by analysis of the P1-HC region. Restriction fragment length polymorphism
      analysis of 363 isolates revealed that the MDMV population consisted of 69
      haplotypes. Sequence analysis of 112 isolates confirmed a high degree of
      nucleotide sequence diversity (0.143), which was higher for P1 than for the HC.
      Twelve sequences showed a single different recombination event. Selection
      pressure analysis revealed that the P1-HC region was under strong negative
      selection. The MDMV population was spatially structured but not structured
      temporally or by host. Phylogenetic analysis split the sequences into five major
      groups.

PMID- 22855127
TI  - Child contact centers and domestic abuse: victim safety and the challenge to
      neutrality.
AB  - Child contact with a nonresident father who has perpetrated domestic abuse has
      gained policy and research attention. Both feminist social policy and family law
      research identify the role child contact centers can play in facilitating contact
      in these circumstances. Drawing from a literature review carried out by the
      authors, this article examines the priorities that underpin feminist social
      policy and family law disciplines and how these manifest in research on contact
      centers and domestic abuse.

PMID- 22855129
TI  - Brachial-ankle pulse wave velocity and brachial pre-ejection period to ejection
      time ratio with renal outcomes in chronic kidney disease.
AB  - Heart failure and increased arterial stiffness are associated with declining
      renal function. This longitudinal study was designed to assess whether the
      combination of brachial-ankle pulse wave velocity (baPWV) and the ratio of
      brachial pre-ejection period (bPEP) to brachial ejection time (bET) was
      independently associated with renal outcomes in patients with chronic kidney
      disease (CKD), stages 3-5. The baPWV and bPEP/bET values were measured using an
      ankle-brachial index (ABI)-form device in 186 patients who were classified into 4
      groups according to the baPWV and bPEP/bET median values. Renal function change
      was determined by estimated glomerular filtration rate (eGFR) slope. Rapid renal
      progression was defined as an eGFR slope less than -3 ml min(-1) per 1.73 m(2)
      per year. The renal endpoints were defined as commencement of dialysis or ?25%
      decline in eGFR. Among the four study groups, the group with high baPWV and
      bPEP/bET values had the lowest eGFR slope (P?0.042). Multivariate analysis
      revealed that this group was independently associated with rapid renal
      progression (odds ratio, 9.560; P=0.009) and progression to renal endpoints
      (hazard ratio, 2.587; P=0.039). Our findings show that a combination of high
      baPWV and bPEP/bET is associated with adverse renal outcomes in patients with
      advanced CKD. Screening CKD patients by baPWV and bPEP/bET during the same
      examination may help identify patients with an elevated risk for adverse renal
      outcomes.

PMID- 22855128
TI  - cry1 and GPA1 signaling genetically interact in hook opening and anthocyanin
      synthesis in Arabidopsis.
AB  - While studying blue light-independent effects of cryptochrome 1 (cry1)
      photoreceptor, we observed premature opening of the hook in cry1 mutants grown in
      complete darkness, a phenotype that resembles the one described for the
      heterotrimeric G-protein alpha subunit (GPA1) null mutant gpa1. Both cry1 and
      gpa1 also showed reduced accumulation of anthocyanin under blue light. These
      convergent gpa1 and cry1 phenotypes required the presence of sucrose in the
      growth media and were not additive in the cry1 gpa1 double mutant, suggesting
      context-dependent signaling convergence between cry1 and GPA1 signaling pathways.
      Both, gpa1 and cry1 mutants showed reduced GTP-binding activity. The cry1 mutant
      showed wild-type levels of GPA1 mRNA or GPA1 protein. However, an anti-transducin
      antibody (AS/7) typically used for plant Galpha proteins, recognized a 54 kDa
      band in the wild type but not in gpa1 and cry1 mutants. We propose a model where
      cry1-mediated post-translational modification of GPA1 alters its GTP-binding
      activity.

PMID- 22855130
TI  - Empirical Studies of Self-Stigma Reduction Strategies: A Critical Review of the
      Literature.
AB  - OBJECTIVE: The purpose of this article was to comprehensively review published
      literature about strategies to reduce self-stigma among people with mental
      illness. Recommendations and implications for research also are discussed.
      METHODS: The electronic databases of Ovid, PubMed, and PsycINFO were searched for
      peer-reviewed articles published between January 2000 and August 2011 by using
      the key words "self-stigma," "internalized stigma," "perceived stigma," and
      "stigma intervention." The search was further narrowed to studies that described
      a detailed intervention and that used self-stigma as a primary or secondary
      outcome, tested the intervention among individuals with a psychiatric illness,
      and analyzed data quantitatively with acceptable statistical tools. RESULTS:
      Fourteen articles met inclusion criteria, and eight reported significant
      improvement in self-stigma outcomes. Participants predominantly had schizophrenia
      and related disorders or depression. Six self-stigma reduction strategies were
      identified. Psychoeducation was the most frequently tested intervention. Self
      stigma definitions, measurements, and conceptual frameworks varied considerably
      across these studies. Several studies lacked a theoretical framework for their
      intervention. Six different scales were used to measure self-stigma. CONCLUSIONS:
      Two prominent approaches for self-stigma reduction emerged from our review: one,
      interventions that attempt to alter the stigmatizing beliefs and attitudes of the
      individual; and two, interventions that enhance skills for coping with self
      stigma through improvements in self-esteem, empowerment, and help-seeking
      behavior. The second approach seems to have gained traction among stigma experts.
      Targeting high-risk groups to preempt self-stigma appears to be a promising area
      for future research.

PMID- 22855132
TI  - Diffuse dermal angiomatosis in a patient with an iatrogenic arterio-venous
      fistula and Wegener's granulomatosis.

PMID- 22855133
TI  - Cancer of unknown primary originating from oropharyngeal carcinomas are strongly
      correlated to HPV positivity.
AB  - Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma
      (OSCC) has been identified as a distinct entity within squamous cell carcinoma of
      the head and neck. It is associated with special characteristics and is
      preponderantly restricted to palatial tonsils and base of tongue. These primary
      locations have for long been associated with the clinical situation of cancer of
      unknown primary (CUP). In order to investigate the putative relationship between
      CUP and HPV, we investigated 26 patients who initially presented as CUP and were
      finally diagnosed with carcinomas of these two locations. Twenty-one cases proved
      to be positive for high-risk HPV. Primary carcinomas were small and frequently
      presented in a submucosal location. HPV-positive carcinomas, presented more often
      in women, showed atypical basaloid differentiation and correlated to cystic lymph
      node metastases. This study demonstrates an over-representation of HPV-associated
      OSCC in patients who were initially diagnosed with CUP. This finding indicates a
      strong relationship between HPV-association and CUP in OSCC. The frequent
      manifestation as CUP is presumably caused by the unusual predisposition for small
      size and submucosal location combined with early lymphatic metastization. In
      order not to miss clinically occult carcinomas, consequent interdisciplinary
      cooperation in combination with meticulous histological workup is mandatory.

PMID- 22855134
TI  - LGR4 and LGR6 are differentially expressed and of putative tumor biological
      significance in gastric carcinoma.
AB  - Gastric cancer (GC) is one of the most common causes of cancer-related deaths
      worldwide. We investigated the differential expression and putative tumor
      biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e.,
      LGR4, LGR6, GPR34, GPR160, and GPR171. Based on our previous microarray analyses,
      we identified five candidate genes in human GC samples. Real-time RT-PCR was
      carried out to validate their expression in malignant and non-malignant tissues
      on an independent collective comprising 32 GC patients with and without lymph
      node metastases. Selected protein targets LGR4 and LGR6 were further validated on
      paraffin-embedded sections of ten intestinal and ten poorly cohesive (diffuse)
      type GCs and their corresponding non-malignant tissue using immunohistochemistry.
      Additionally, the putative tumor biological significance of LGR4 and LGR6 was
      studied using tissue microarrays obtained from a cohort of 481 GC patients. On
      transcriptional level, GPR34, GPR160, and GPR171 were not differentially
      expressed in GC compared with non-neoplastic mucosa. LGR4 and LGR6 were up
      regulated on transcriptional (real-time RT-PCR) and translational
      (immunohistochemistry) levels in GC. Furthermore, in tissue microarray analysis,
      LGR6 expression was significantly associated with local tumor growth (T-category;
      p = 0.04) and correlated with patient survival. LGR4 expression was significantly
      correlated with nodal spread (N-category; p = 0.025). Our systematic analysis
      indicates that LGR4 and LGR6 may play a role in GC biology. Future studies will
      have to demonstrate whether these are also putative diagnostic, prognostic,
      and/or therapeutic targets for GC.

PMID- 22855135
TI  - Hereditary pancreatic cancer: molecular bases and their application in diagnosis
      and clinical management: a guideline of the TTD group.
AB  - Pancreatic carcinoma (PC) represents the fourth leading cause of cancer death in
      Spain with a death rate of 2,400 males and 2,000 females per year. Poor outcome
      related to its silent nature and the lack of reliable secondary prevention
      measures translate into advanced-stage diagnosis, 75 % of deaths within the first
      year of diagnosis and 5-year survival rate of <5 %. Family history was first
      recognized as a risk factor for PC. Further population-based and case-control
      studies subsequently found that 7.8 % of patients with PC have a family history
      of the same tumor and individuals with a first-degree relative with PC have a 3.2
      fold increased risk of developing PC. Overall, it is estimated that up to 10 % of
      PC have a familial component. However, known genetic syndromes account for <20 %
      of the observed familial aggregation of PC. We review the most important aspects
      in epidemiology, molecular biology and clinical management of familial PC.

PMID- 22855136
TI  - Surveillance of resected non-small cell lung cancer.
AB  - Lung cancer is the most common cancer in the world. 15 % of all patients with
      lung cancer are diagnosed at an early stage, and surgery is the treatment of
      choice for them. 40 % of all patients survive more than 5 years after surgery,
      and most of them die as a result of systemic disease. Half of all recurrences are
      diagnosed within the first 24 months after curative treatment, and 90 % in the
      first 5 years. Despite this, it is not standardized who should do the monitoring,
      what additional tests are needed and how often should they be performed. We
      present here a review on the various recommendations in clinical guidelines.

PMID- 22855138
TI  - A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and
      leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line
      chemotherapy for advanced colorectal cancer.
AB  - INTRODUCTION: The aim of this study was to compare TOMOX versus FOLFOX4 as first
      line treatment of advanced colorectal cancer (CRC). MATERIALS AND METHODS: 191
      chemotherapy-naive patients were randomized to receive TOMOX or FOLFOX4. Patients
      were evaluated every 3 months and chemotherapy was continued until disease
      progression or unacceptable toxicity. Overall response rate was the primary
      endpoint. RESULTS: 183 patients were included in the intent-to-treat analysis (92
      TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for
      TOMOX and FOLFOX4, respectively. No statistically significant differences were
      observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free
      survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6
      months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4
      neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the
      FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group
      (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in
      the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences
      between the two regimens for physical and mental composite scores after 6 weeks,
      and for body pain and emotional role functioning after 6 and 12 weeks; all of
      these favored the FOLFOX4 arm (p <= 0.05). CONCLUSIONS: TOMOX and FOLFOX4 seem to
      have similar efficacy and are well tolerated in the first-line treatment for
      advanced CRC with different profiles of toxicity. The convenient TOMOX regimen
      may offer an alternative to fluoropyrimidine-based regimens.

PMID- 22855137
TI  - Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC).
AB  - Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the
      sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies
      and a new generation of tyrosine kinase inhibitors, have been shown in phase II
      trials to be safe and effective in the treatment of advanced hepatocellular
      carcinoma. Several currently active phase III trials are testing these drugs,
      both in first- and second-line settings. Strategies to overcome primary and
      acquired resistance to antiangiogenic therapy are urgently needed. Novel
      biomarkers may help in improving the efficacy of drugs targeting angiogenesis.

PMID- 22855139
TI  - Recombinant human endostatin could eliminate the pro-angiogenesis priority of SP
      cells sorted from non-small cell lung cancer cells.
AB  - PURPOSE: To ascertain the biologic significance of lung cancer Side population
      (SP) cells, which represent putative cancer stem cells (CSC) in the absence of
      consensus biomarkers for tumor-specific CSC. MATERIALS AND METHODS: We sorted and
      analyzed the angiogenic features of SP cells, isolated from tumor cell lines
      based on the exclusion of the DNA dye Hoechst 33342, from the NSCLC cell lines
      A549 and H460. RESULTS: Compared with non-SP cells, mRNA of vascular endothelial
      growth factor (VEGF)-A, VEGF-B, angiopoietin (ang)-1, ang-2, fibroblast growth
      factor-2 (FGF-2), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8) were over
      expressed in SP cells accompanied by over-expression of ABCG2 and MDR1 mRNA. The
      supernatant of cultured SP cells could significantly induce migration of human
      umbilical vein endothelial cells, while recombinant human endostatin (Endostar
      25((r))) could inhibit the migration. CONCLUSIONS: This study revealed that the
      NSCLC SP cells might represent CSCs and possess pro-angiogenic properties, and
      antiangiogenesis represent a potential therapy.

PMID- 22855140
TI  - BIK/NBK gene as potential marker of prognostic and therapeutic target in breast
      cancer patients.
AB  - PURPOSE: The purpose of this study is to determine the association between the
      BIK/NBK gene expression and estrogen receptor alpha expression. MATERIALS AND
      METHODS: We determined the association of BIK/NBK gene expression by real time
      quantitative reverse transcription polymerase chain reaction and estrogen
      receptor alpha expression by immunohistochemistry in samples of breast cancer
      tissue. RESULTS: We found a statistically significant correlation of BIK/NBK gene
      expression with the estrogen receptor alpha expression (rho = 0.751, p = 0.004).
      For verify differences of BIK/NBK gene expression among ERalpha+ and ERalpha-
      breast cancer tissues, Mann-Whitney U test was performed, obtaining significant
      differences. CONCLUSIONS: BIK/NBK gene expression may have important clinical
      implications and provide predictive, prognostic or therapeutic marker in breast
      cancer patients according to the estrogen receptor alpha expression.

PMID- 22855141
TI  - Phase II study of preoperative radiotherapy and concomitant weekly intravenous
      oxaliplatin combined with oral capecitabine for stages II-III rectal cancer.
AB  - INTRODUCTION: A prospective phase II study was conducted to assess the clinical
      activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for
      neoadjuvant therapy of stages II-III rectal cancer. MATERIALS AND METHODS:
      Patients with histologically confirmed stages II-III (T3-T4 and/or N+) resectable
      rectal adenocarcinoma were eligible. Capecitabine was administered at 825 mg/m(2)
      twice daily for 5 days/week and oxaliplatin at 50 mg/m(2) on day 1 weekly for 5
      weeks starting the first day of RT (before RT). RT consisted of a total dose of
      45 Gy delivered in 25 fractions of 1.8 Gy, 5 days per week, for 5 weeks. RESULTS:
      A total of 46 patients were included (35 male, 10 female, median age 62 years).
      TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected
      nodal involvement. The intended chemoradiation treatment was completed in 94 %
      patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4
      patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and
      hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients,
      Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2.
      Forty-two patients underwent surgery (complete resection 95 %, sphincter-saving
      operation 55 %). The overall pathologic response rate was 83 %, with a pathologic
      complete response (pCR) rate of 11.9 % (95 % CI 4.0-25.6). CONCLUSIONS: The pCR
      rate observed with oxaliplatin plus capecitabine and RT did not reach the pre
      specified criteria of efficacy in this trial, which is in line with recent
      results of randomized phase III trials.

PMID- 22855142
TI  - Chemotherapy at the end of life: up until when?
AB  - AIM: The aim of this study is to analyze the use of CT in terminal stage cancer
      and the percentage of patients who received UCPD in 2009 and 2010 on the Medical
      Oncology and Palliative Home Care integrated service (UCPD) ward of the Marques
      de Valdecilla University Hospital. METHOD: Retrospective analysis of death rate
      registered on the Medical Oncology ward for 2009 and 2010 and the recorded date
      of the last CT given. The data are analyzed using the SPSS version 15.0 statistic
      package. Data were obtained from the Database Minimum Set for oncology
      admissions. RESULTS: The death rate on the Medical Oncology ward is 22-24%. Total
      number of cases studied is 303. 47% of patients are aged 60 or younger. 81.8%
      (248) received active cancer treatment; of these, 138 (55.6%) in the last month,
      and 84 (33.8%) in the last 2 weeks. Only 66 patients out of those who died on the
      ward (21%) were previously sent to the UCPD. CONCLUSIONS: Even when it is known
      that the majority of cancer patients become resistant to CT at the end of their
      lives, it is often given to patients of all ages. The request for palliative care
      is rare and often late.

PMID- 22855143
TI  - Toxicity of concurrent hyperfractionated radiation therapy and chemotherapy in
      locally advanced (stage III) non-small cell lung cancer (NSCLC): single
      institution experience in 600 patients.
AB  - PURPOSE: to investigate toxicity of hyperfractionated radiation therapy (Hfx RT)
      with or without concurrent chemotherapy (CHT) in patients with locally advanced
      non-small cell lung cancer (NSCLC) and factors independently influencing it.
      MATERIALS AND METHODS: Of a total of 600 patients treated during five prospective
      studies Hfx RT alone was given in 127 and Hfx RT-CHT was given in 473 patients.
      Hfx RT doses were 64.8 and 69.6 Gy (1.2 Gy bid) and 67.6 Gy (1.3 Gy bid). CHT
      administration consisted of concurrent carboplatin and etoposide in 409 patients
      and concurrent carboplatin and paclitaxel in 64 patients. RESULTS: Acute
      oesophageal toxicity was significantly increased with concurrent CHT (p = 0.034),
      as well as bronchopulmonary (p = 0.044) and haematological toxicity (p < 0.001).
      Only late high-grade bronchopulmonary (p = 0.007) toxicity was significantly more
      frequent in the RT-CHT group. Only acute high-grade haematological toxicity was
      significantly more frequent in split CHT than in daily CHT and Hfx RT alone (p <
      0.001). Only late high-grade bronchopulmonary toxicity remained significantly
      more frequent in both Hxf RT-CHT groups than in Hfx RT alone. No variable
      influenced acute high-grade bronchopulmonary, gastric or skin toxicity.
      Pronounced weight loss influenced increased acute high-grade oesophageal
      toxicity. Increased weight loss and lower KPS influenced increased haematological
      toxicity. Pronounced weight loss and concurrent CHT influenced increased late
      high-grade bronchopulmonary toxicity. CONCLUSIONS: This study reconfirmed low
      acute and late high-grade toxicity in stage III NSCLC treated with concurrent RT
      CHT and identified factors influencing it.

PMID- 22855144
TI  - Fifty percent patients avoid whole brain radiotherapy: stereotactic radiotherapy
      for multiple brain metastases: a retrospective analysis of a single center.
AB  - PURPOSE: To summarize the outcomes of stereotactic radiotherapy (SRT), with or
      without whole-brain radiotherapy (WBRT), in the treatment of multiple brain
      metastasis and to explore the status of WBRT and SRT in the management of
      multiple brain metastasis. METHODS: From May 1995 to April 2010, 98 patients with
      newly diagnosed, multiple brain metastasis were treated in our center. Forty-four
      patients were treated with SRT alone for the initial treatment, and 54 were
      treated with SRT + WBRT. Kaplan-Meier and Cox proportional hazards regression
      analyses were used for the survival analysis. RESULTS: The median survival time
      (MST) was 13.5 months. No difference was observed in MST between the SRT and the
      SRT + WBRT groups (p = 0.578). The Karnofsky Performance Score at the time of
      treatment (p = 0.025), the interval time between diagnosis of primary tumor and
      brain metastasis (P = 0.012) and the situation of extracranial disease (p =
      0.018) were significant predictors of survival. The crude distant intracranial
      recurrence (DIR) rates were 47.7 % in the SRT group and 24.1 % in the SRT + WBRT
      group (p = 0.018). In addition, 52.3 % patients in the SRT group were free from
      DIR and did not require WBRT in their whole lives. CONCLUSIONS: Our data suggest
      that use of SRT as the initial treatment while reserving WBRT as the salvage
      therapy in case of distant intracranial recurrence made about 50 % of the
      patients avoid WBRT throughout the course of their lives and may be another
      optional treatment modality for multiple brain metastases.

PMID- 22855145
TI  - Trends in the lung cancer incidence and mortality in the Slovak and Czech
      Republics in the contexts of an international comparison.
AB  - INTRODUCTION: Lung cancer represents the most frequent cause of cancer-related
      deaths in the industrialized countries. The aim of this study was to analyze the
      lung cancer incidence and mortality and the possible reasons for any differences
      discovered in two neighboring Central European countries-the Slovak Republic.
      METHODS: We used linear regression model when analyzing incidence and mortality;
      the trends are presented with corresponding 95% confidence intervals (CI) and p
      value with null hypothesis being constant with time. RESULTS: Statistically
      significant increase of age-standardized incidence (0.707/100,000/year, 95% CI
      0.107-1.307, p = 0,025) and mortality (1.339/100,000/year, 95% CI 1.050-1.629, p
      < 0.0001) of the lung cancer was revealed in males in the Slovak Republic (1980
      1991). On the contrary, values of both indicators were stabilized in the Czech
      Republic. Since year 1991-2005 a statistically highly significant decrease of
      both incidence and mortality values was observed in males, which was greater in
      the Slovak Republic. Peak of the curve was not reached in women population, while
      incidence and mortality values have significantly continuous growth in both
      countries. CONCLUSIONS: According to the lung cancer incidence and mortality
      trends in both countries (in correlation with smoking prevalence) we consider the
      support of efforts to change the attitude towards smoking predominantly in women
      and younger generation to be the most accurate action to reduce these trends.

PMID- 22855146
TI  - Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naive adult
      patients with gastrointestinal stromal tumours (GISTs) of the stomach and small
      intestine: relation to tumour-biological risk-profile and long-term outcome.
AB  - BACKGROUND: The identification of activating mutations in either c-KIT cell
      surface growth factor receptor or platelet-derived growth factor receptor alpha
      (PDGFRA) has lead the way for the development of novel agents that selectively
      inhibit key molecular events in gastrointestinal stromal tumour (GIST)
      pathogenesis. The aim of this study was to investigate the role of c-KIT and
      PDGFRA gene mutations in primary resectable, imatinib naive GISTs located in the
      stomach and small intestine. METHODS: All adult patients with GIST located in
      either stomach or small intestine who underwent surgical resection without prior
      imatinib (Glivec) treatment were included. DNA extraction and mutational analysis
      were performed. Mutational analyses were performed for c-KIT (exons 9, 11, 13,
      and 17) and the PDGFRA genes (exons 12, 14 and 18). Clinical and pathological
      parameters were analyzed in relation to the mutations in c-KIT and PDGFRA.
      RESULTS: A total of 38 patients who underwent surgery for GIST located in either
      the stomach (n = 24) or in the small intestines (n = 14) were included. Mutations
      were found in 31 of 38 (81.6 %) patients, with 24 (63.2 %) located in c-KIT and 7
      (18.4 %) in the PDGRFA exons, respectively. Seven patients (18.4 %) were wildtype
      (WT). The most common mutation was in c-KIT exon 11. Incidentally found GISTs
      were significantly smaller (size >5 cm in 15 % for incidental vs. 71 % for
      symptomatic; OR of 13.4, 95 % CI 2.3-76.5; P = 0.001) and had lower mitotic rate
      (0 % for incidental vs. 44 % of the symptomatic; OR 0.52, 95 % CI 0.36-0.75; P =
      0.005). Accordingly, the Fletcher grade was significantly better for incidental
      cases, with most having very low or low risk (85 %) in contrast to 19 of 25 (76
      %) symptomatic cases showing moderate to high-risk features (OR 17.4, 95 % CI
      2.98-101.7; P < 0.001). However, the distribution of c-KIT, PDGFRA and WT was not
      differently distributed between incidental and symptomatic GISTs. Long-term
      survival up to 25 years (median: 8 years) was best determined by Fletcher risk
      score in the multivariate model (HR 14.1, 95 % CI 1.7-114.5; p = 0.013).
      CONCLUSIONS: Long-term survival in resected GISTs of the stomach and small
      intestine is best determined by Fletcher risk-score. Mitotic activity appears
      related to tumour size and young age at onset. Mutational status did not
      influence the clinical or tumour-specific features in this cohort.

PMID- 22855148
TI  - Clinical safety of induced CTL infusion through recombinant adeno-associated
      virus-transfected dendritic cell vaccination in Chinese cancer patients.
AB  - AIM: The aim of the study is to explore the safety of cytotoxic T lymphocytes
      (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno
      associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients.
      PATIENTS AND METHODS: A total of 27 cancer patients with tumor tissue expression
      positivity and/or sera-elevated level of CEA were subsequently divided into
      cohort A and B resulted from the ex vivo expansion number of CTLs generated from
      co-culture of specific transfected DCs with autologous T lymphocytes. Based on
      the variations of infused number of specific CTL derived from different yields of
      individualized patients who had experienced various anti-cancer treatments, we
      compared the patients of low number of CTL cells (2-8 * 10(8) infused, cohort A,
      6 cases) with those of higher number (above 8 * 10(8) infused, cohort B, 21
      cases) to testify the possible adverse reactions caused by amount of infused
      CTLs. This study resembled a phase I study aiming for setting up clinical trial
      of adoptive cellular therapy that conceptually comes from conventional cytotoxic
      drugs. RESULTS: The results showed that one case from the each cohort had
      experienced moderate fever, and four cases with fatigue were seen in cohort B.
      The symptoms were transient without serious adverse events. For the consideration
      of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9
      stable disease (40 %, 10/25) were observed in 25 patients eligible for
      evaluation. Sera levels of CEA assay were lowered in six patients. During a
      median follow-up of 8.1 months, we could not observe severe or chronic adverse
      reactions related to rAAV-DC infusions. Meanwhile, the variation of number of
      CTLs infused in this setting did not alter the status of peripheral lymphocyte
      population. CONCLUSIONS: These preliminary data suggest that the rAAV-DC
      immunotherapy is well-tolerated and showed no severe adverse reactions in cancer
      patients.

PMID- 22855149
TI  - The association of annexin A2 and cancers.
AB  - Annexins are a group of calcium- and phospholipid-dependent proteins. As a member
      of the annexin, annexin A2 (Anxa2) is widely distributed in nucleus, cytoplasm
      and extracellular surface and mainly expressed in human endothelial cells,
      mononuclear cells, macrophages, marrow cells and some tumor cells. Accumulated
      evidences indicated that Anxa2 deregulation was associated with the occurrence,
      invasion and metastasis of cancers. Anxa2 up-regulation was related to the
      development, invasion, metastasis and drug resistance of hepatocellular
      carcinoma, colorectal cancer, breast cancer, pancreatic cancer, acute
      promyelocytic leukemia and renal cell carcinoma; while Anxa2 down-regulation was
      associated with prostate cancer, esophageal squamous carcinoma and nasopharyngeal
      carcinoma and sinonasal adenocarcinoma. The association between Anxa2 and
      malignant tumors as well as the potential action mechanisms were summarized in
      current work. Anxa2 might be used as a potential biomarker for the diagnosis,
      treatment and prognosis of certain tumors.

PMID- 22855150
TI  - Guidelines for biomarker testing in colorectal carcinoma (CRC): a national
      consensus of the Spanish Society of Pathology (SEAP) and the Spanish Society of
      Medical Oncology (SEOM).
AB  - This consensus statement, conceived as a joint initiative of the Spanish Society
      of Pathology and the Spanish Society of Medical Oncology, makes diagnostic and
      treatment recommendations for the management of patients with hereditary,
      localised and advanced CRC based on the current scientific evidence on biomarker
      use. This consensus statement thus provides an opportunity to improve healthcare
      efficiency and resource use, which will benefit these patients. Based on the
      currently available data on this subject, this expert group recommends testing
      for microsatellite instability (MSI) in patients with localised CRC, as this is a
      strong predictive factor for deciding on adjuvant treatment. However, although
      the ColoPrint((r)) and Oncotype Dx((r)) gene expression signatures have been
      shown to have prognostic value, no consensus yet exists concerning their use in
      clinical practice. For advanced CRC, it is essential to test for KRAS mutation
      status before administering an anti-EGFR treatment, such as cetuximab or
      panitumumab. However, testing for other biomarkers, such as BRAF, EGFR, PI3K and
      PTEN mutations, should not be done routinely, because this does not influence
      treatment planning at the present time. Other important issues addressed include
      organisational requirements and the quality controls needed for proper testing of
      these biomarkers as well as the legal implications to be borne in mind when
      testing some biomarkers.

PMID- 22855151
TI  - Incidence of hand-foot syndrome with capecitabine in combination with
      chemotherapy as first-line treatment in patients with advanced and/or metastatic
      gastric cancer suitable for treatment with a fluoropyrimidine-based regimen.
AB  - INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine,
      which is not life-threatening but could compromise capecitabine efficacy.
      MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed
      the safety, particularly grade three HFS incidence, and efficacy of four
      capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX),
      epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine
      (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for
      advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight
      patients were assigned to one of the four treatment groups, according to
      investigator's criteria, and grouped together for both safety and efficacy
      primary analyses. HFS was reported in 31 patients (19.6%) and its first
      presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS
      developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX
      chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation
      due to HFS was required in 5.7% of patients (9/158). The most common (> 10%)
      grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and
      diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in
      patients treated with capecitabine, which generally presented late and required
      dose reduction in < 1/3 of patients. The results suggest that capecitabine may be
      useful in combination with standard fluorouracil-based regimens in patients with
      advanced and/or metastatic gastric cancer with favourable safety profile.

PMID- 22855152
TI  - Immunohistochemical expression of cyclooxygenase-2 in patients with advanced
      cancer of the larynx who have undergone induction chemotherapy with the intention
      of preserving phonation.
AB  - INTRODUCTION: Cyclooxygenase-2 (COX2) is an enzyme that plays a role in different
      stages of the carcinogenic process and has prognostic and predictive values that
      have not yet been established. The objective of this study was to evaluate the
      role of COX2 overexpression in advanced squamous cell carcinoma of the larynx
      that has been treated with a phonation conservation protocol. MATERIALS AND
      METHODS: This study included a retrospective analysis of 59 patients with
      resectable tumours that were treated with chemotherapy (CT) and/or radiation
      therapy (RT). The expression levels of COX2, epidermal growth factor receptor
      (EGFR), vascular endothelial growth factor (VEGF), and vascular endothelial
      growth factor receptor (VEGFR-2) in collected biopsy specimens were determined
      via immunohistochemistry. RESULTS: Forty-four percent of the included samples
      demonstrated overexpression of COX2. In the statistical analysis, COX2
      overexpression did not correlate with other clinical or treatment efficacy
      prognostic factors; however, the median global survival (OS) of patients whose
      tumours expressed COX2 was 79 months, whereas COX2-negative patients had a median
      OS of only 38 months, although this finding did not reach statistical
      significance. The other analysed biological parameters did not demonstrate a
      significant relationship with COX2. CONCLUSIONS: COX2 overexpression was a common
      finding in our study. The results obtained did not reveal relationships with
      established prognostic categories; however, the difference in survival between
      patients with and without COX2 expression justifies the need for future
      prospective studies that utilise a larger patient sample size.

PMID- 22855153
TI  - Murine bone marrow stromal cells pulsed with homologous tumor-derived exosomes
      inhibit proliferation of liver cancer cells.
AB  - BACKGROUND: Increasing evidence shows that bone marrow stromal cells (BMSCs) have
      antitumor activities both in vitro and in animal models. Further studies fleshed
      out the supportive data that the antitumor activity of BMSCs could be markedly
      enhanced by cytokines such as IL-2 and IFN-beta (interferon). However, powerful
      strategies to activate BMSCs other than by genetically engineering interventions
      are still required. METHODS: In this study, new methods of generating antitumor
      activities of murine marrow-originated MSCs pulsed with homologous tumor-derived
      exosomes (TEX) were explored to yield potent immune effectors against
      hepatocellular carcinoma cells in vitro. RESULTS: The results showed that BMSCs
      pulsed with exosomes and IFN-gamma exhibited increased migration ability with a
      result of 163.22 +/- 26.90 versus 129.89 +/- 29.28 cells/HP by transwell
      determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma
      cells line H(22) cells by exosomes pulsed BMSCs was significantly increased by
      41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that
      the cell cycle of H(22) cells was arrested in G(0)/G(1) phase. Meanwhile, western
      blot analysis showed that PCNA protein expression in the supernatant of H(22)
      cells was significantly decreased. CONCLUSIONS: This study demonstrated that
      BMSCs pulsed with TEX could enhance its antitumor activities, which might be
      regarded as a novel promising antitumor treatment.

PMID- 22855154
TI  - Intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB)
      in a patient with left breast cancer and pectus excavatum.
AB  - INTRODUCTION: Pectus excavatum is a frequent anomaly. It represents a challenge
      for adjuvant radiotherapy in the conservative treatment of breast cancer. Primary
      objective of this study is to compare dosimetric outcomes, normal tissue
      complication probability (NTCP), and integral dose using four radiation
      techniques. Secondary objective is to describe acute toxicity and setup errors.
      METHODS AND MATERIALS: A 57-year-old female patient with an inner quadrant, left
      breast, ductal carcinoma in situ, was identified. Whole breast was prescribed
      with 50 Gy in 25 fractions. Boost planning target volume (PTV) was prescribed
      with 60 Gy in 30 fractions for sequential boost (SB) plans or 57.5 Gy in 25
      fractions in the simultaneous integrated boost (SIB) plan. All plans were
      normalized to deliver 47.5 Gy to 95 % of the breast PTV. Daily image-guided
      radiotherapy (IGRT) was performed. Setup deviations were described. RESULTS:
      Constraints were not accomplished for heart when using intensity modulated
      radiotherapy (IMRT) + SB or conformal radiotherapy with three photon fields and
      SB. Left lung constraint was not achieved by any of the techniques in comparison.
      IMRT + SIB and conformal photons and electrons + SB plan were closer to the
      objective. Integral doses were lower with IMRT for heart and ipsilateral lung;
      however, it were higher for contralateral breast and lung. Coverage and tumoral
      conformity indexes were similar for all techniques in comparison. Greater
      inhomogeneity was observed with the photons and electrons + SB. IMRT + SIB
      treatment was administered daily with grade I skin toxicity. The highest setup
      error was observed in Y direction. CONCLUSION: Planning target volume coverage
      was similar with the four techniques. Homogeneity was superior with both IMRT
      plans. A good balance between dose constraints for organs at risk, PTV coverage,
      homogeneity, and NTCP was observed with IMRT + SIB. The documented daily setup
      error justifies the use of online IGRT.

PMID- 22855155
TI  - The SGBS cell strain as a model for the in vitro study of obesity and cancer.
AB  - INTRODUCTION: The murine adipocyte cell line 3T3-L1 is well characterised and
      used widely, while the human pre-adipocyte cell strain, Simpson-Golabi-Behmel
      Syndrome (SGBS), requires validation for use in human studies. Obesity is
      currently estimated to account for up to 41 % of the worldwide cancer burden. A
      human in vitro model system is required to elucidate the molecular mechanisms for
      this poorly understood association. This work investigates the relevance of the
      SGBS cell strain for obesity and cancer research in humans. MATERIALS AND
      METHODS: Pre-adipocyte 3T3-L1 and SGBS were differentiated according to standard
      protocols. Morphology was assessed by Oil Red O staining. Adipocyte-specific gene
      expression was measured by qPCR and biochemical function was assessed by glycerol
      3-phosphate dehydrogenase (GPDH) enzyme activity. Differential gene expression in
      oesophageal adenocarcinoma cell line OE33 following co-culture with SGBS or
      primary omental human adipocytes was investigated using Human Cancer Profiler
      qPCR arrays. RESULTS: During the process of differentiation, SGBS expressed
      higher levels of adipocyte-specific transcripts and fully differentiated SGBS
      expressed more similar morphology, transcript levels and biochemical function to
      primary omental adipocytes, relative to 3T3-L1. Co-culture with SGBS or primary
      omental adipocytes induced differential expression of genes involved in adhesion
      (ITGB3), angiogenesis (IGF1, TEK, TNF, VEGFA), apoptosis (GZMA, TERT) and
      invasion and metastasis (MMP9, TIMP3) in OE33 tumour cells. CONCLUSIONS:
      Comparable adipocyte-specific gene expression, biochemical function and a shared
      induced gene signature in co-cultured OE33 cells indicate that SGBS is a relevant
      in vitro model for obesity and cancer research in humans.

PMID- 22855156
TI  - Outcomes and prognostic factors of conformal radiotherapy versus intensity
      modulated radiotherapy for nasopharyngeal carcinoma.
AB  - INTRODUCTION: This study retrospectively compared outcomes and prognostic factors
      of nasopharyngeal carcinoma (NPC) treated with conformal radiotherapy (CRT) and
      intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: The treatment
      records of 182 patients treated with IMRT and 198 patients treated with CRT from
      April 2005 to December 2007 in our hospital were reviewed. The clinical
      characteristics, treatment outcomes (including survival analysis and acute and
      late toxicity), and prognostic factors of the two groups were compared. RESULTS:
      The 4-year local-regional control (LRC), distant metastasis-free survival (DMFS),
      disease-free survival (DFS), and overall survival (OS) of the IMRT and CRT groups
      were 93.6 and 85.3 %, 79.1 and 73.6 %, 74.7 and 65.0 %, and 83.5 and 72.1 %,
      respectively. The acute radiation dermatitis and xerostomia of the two groups
      were significantly different (P < 0.05). In the IMRT group, OS between different
      T stages could not be well separated. Multivariate analysis revealed that, in the
      CRT group, the clinical stage and T and N stages were significant prognostic
      factors for OS, DMFS, and DFS and that T stage was a significant prognostic
      factor for LRC. In the IMRT group, T and N stages had no predictive value for
      outcomes. CONCLUSIONS: Compared with CRT, IMRT has a better prognosis and less
      adverse effects. For IMRT, T stage was not a significant prognostic factor for
      LRC, DMFS, DFS, or OS. An effective treatment strategy is needed for distant
      control. With the increasing use of IMRT and continued modulation of treatment
      strategies for NPC, the current staging system faces great challenges.

PMID- 22855157
TI  - Defects in mTR stability and telomerase activity produced by the Dkc1 A353V
      mutation in dyskeratosis congenita are rescued by a peptide from the dyskerin
      TruB domain.
AB  - BACKGROUND: The predominant X-linked form of dyskeratosis congenita results from
      mutations in dyskerin, a protein required for ribosomal RNA modification that is
      also a component of the telomerase complex. We have previously found that
      expression of an internal fragment of dyskerin (GSE24.2) rescues telomerase
      activity in X-linked dyskeratosis congenita (X-DC) patient cells. MATERIALS AND
      METHODS: Here, we have generated F9 mouse cell lines expressing the most frequent
      mutation found in X-DC patients, A353V and study the effect of expressing the
      GSE24.2 cDNA or GSE24.2 peptide on telomerase activity by TRAP assay, and mTERT
      and mTR expression by Q-PCR. Point mutation in GSE24.2 residues were generated by
      site-directed mutagenesis. RESULTS: Expression of GSE24.2 increases mTR and to a
      lesser extent mTERT RNA levels, and leads to recovery of telomerase activity.
      Point mutations in GSE24.2 residues known to be highly conserved and crucial for
      the pseudouridine-synthase activity of dyskerin abolished the effect of the
      peptide. Recovery of telomerase activity and increase in mTERT levels were found
      when the GSE24.2 peptide purified from bacteria was introduced into the cells.
      Moreover, mTR stability was also rescued by transfection of the peptide GSE24.2.
      DISCUSSION: These data indicate that supplying GSE24.2, either from a cDNA
      vector, or as a peptide, can reduces the pathogenic effects of Dkc1 mutations and
      could form the basis of a novel therapeutic approach.

PMID- 22855158
TI  - Prognostic value of clinicopathological parameters and outcome in 484 patients
      with oral squamous cell carcinoma: microvascular invasion (V+) is an independent
      prognostic factor for OSCC.
AB  - BACKGROUND: Several clinicopathological parameters have been implicated in
      prognosis, recurrence and survival, following oral squamous cell carcinoma
      (OSCC). The purpose of this retrospective study was to review the outcome of
      patients with oral cavity squamous cell carcinoma treated at a single institution
      by primary surgical resection with or without adjuvant radiotherapy or
      radiochemotherapy, or brachytherapy and to identify the factors affecting
      survival and locoregional control. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 429 consecutive patients after primary radical R0 tumor
      resection and 55 patients after brachytherapy in our department between 1997 and
      2010. OSCC pathological parameters were analyzed including age, gender, site
      distribution, tumor size, lymph node involvement, grading, microvascular
      invasion, lymphatic vessel involvement, and distant metastasis. Descriptive
      statistics were calculated for each variable and survival was calculated using
      the univariate Kaplan-Meier method. Prognostic factors were analyzed using the
      multivariate Cox proportional hazard model. RESULTS: Average tumor size was 10.9
      mm (95 % CI for the mean 9.6-12.3). Disease-free survival at 5 years was 65 % and
      overall 5-year survival was 62 %. On univariate analysis, patients with increased
      tumor size, lymph node involvement, microvascular invasion, and lymphatic vessel
      involvement had a significant poor prognosis. Multivariate analysis showed that
      independent prognostic factors were increased tumor size and microvascular
      invasion. CONCLUSION: This hospital-based retrospective cohort study points out
      different clinicopathological prognostic factors of survival in a large patient
      cohort treated for OSCC. It highlights increased tumor size and microvascular
      invasion as the most independent prognostic factors in predicting survival in
      patients with OSCC.

PMID- 22855159
TI  - Induced apoptosis in human prostate cancer cells by blocking of vascular
      endothelial growth factor by siRNA.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) regulates several cell
      functions including; proliferation, differentiation, permeability, vascular tone,
      and the production of vasoactive molecules. The purpose of this study was to
      evaluate the potency of specific short-interfering RNA (siRNA) to suppress human
      VEGF expression by siRNA and investigate the effects of VEGF down-regulation on
      the cell proliferation and apoptosis of the human prostate cancer cell lines DU
      145. METHODS: Transfection was performed using X-tremeGENE siRNA transfection
      reagent. At different time intervals, transfected cells were harvested and total
      RNA was extracted for RT-PCR. The VEGF content in supernatants were measured by
      ELISA. Inhibition of cell growth by hVEGF-siRNA was measured by using cell
      proliferation ELISA BrdU assay. Apoptotic cells were evaluated by using annexin-V
      FITC apoptotic detection method. RESULTS: Transfection of hVEGF-siRNA resulted in
      statistically significant inhibition of hVEGF-mRNA that in turn caused a marked
      reduction in the expression of hVEGF. The cell growth was assessed every 24 h for
      4 days after siRNA treatment resulted in a marked inhibition of cell
      proliferation as compared to scramble siRNA. The results of apoptosis showed that
      approximately 15 % of the cells treated with control-siRNA manifested evident
      apoptotic changes after 24 hpt, whereas DU-145 cells treated with hVEGF-siRNA
      significantly were positive, that is to say, 53 % at 72 hpt 23.9 +/- 2.78 % (P <
      0.001) and 13 +/- 1.57 % at 96 hpt. CONCLUSION: Our findings indicate that siRNA
      are effective in eliciting the RNAi pathway in cancerous cells and that specific
      siRNA efficiently down-regulate VEGF expression. They could decrease VEGF
      production and induce apoptosis, which may also be linked to the inhibition of
      cancerous cell proliferation. Therefore, it can be concluded that siRNA-mediated
      suppression of VEGF represents a powerful tool against prostate cancer cell
      proliferation. VEGF down-regulation exerts a direct anti-apoptotic function in
      the DU-145 cell lines and promises the development of drugs for cancer therapy.

PMID- 22855160
TI  - Reduced expression of Raf kinase inhibitor protein correlates with poor prognosis
      in pancreatic cancer.
AB  - AIM: Raf kinase inhibitory protein (RKIP) is an inhibitor of the Raf/MEK/MAP
      kinase signaling cascade and a suppressor of cancer metastasis. But its function
      in pancreatic cancer was not yet clarified completely. The aim of this study was
      to investigate the involvement of RKIP in pancreatic cancer. METHODS: RKIP
      expression was investigated retrospectively by immunohistochemistry in paraffin
      embedded primary tumor tissue samples from a series (n = 99) of consecutive
      patients with pancreatic cancer. Survival was calculated using Kaplan-Meier
      curves. Parameters found to be of prognostic significance in univariate analysis
      were verified in a multivariate Cox regression model. RESULTS: RKIP expression
      was high in normal pancreatic epithelium and retained to varying degrees in
      pancreatic cancer tissues. However, in tumor tissues with lymph node metastasis
      (P = 0.008) and high UICC stage (P = 0.006), RKIP expression was highly
      significantly reduced or lost. Furthermore, the reduced expression of RKIP
      significantly correlated with both poor overall and disease-free survival (P =
      0.008 and 0.01, respectively). Multivariate analyses revealed RKIP to be an
      independent prognosticator. CONCLUSION: These findings suggest that RKIP could be
      a promising marker for predicting a better prognosis in pancreatic cancer.

PMID- 22855161
TI  - Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage
      IV non-small cell lung cancer.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR), an index of systemic
      inflammation, has been associated with worse survival for many types of cancer.
      The aim of this study is to investigate the clinical significance of the blood
      NLR as a prognostic factor in non-small cell lung cancer (NSCLC) patients.
      METHODS AND PATIENTS: Stage IV NSCLC patients diagnosed in our institution
      between April 2004 and March 2009 were retrospectively reviewed. Potential
      prognostic factors such as histology, gender, performance status, response to
      chemotherapy and NLR were analyzed. NLR was assessed baseline and during
      chemotherapy treatment. Overall survival (OS) and progression free survival (PFS)
      were calculated by the Kaplan-Meier method. RESULTS: A total of 171 patients were
      included in the study and 60 patients (35.1 %) presented a NLR >= 5. Median
      survival for the entire cohort was 9.3 months. We found that patients with
      undifferentiated carcinoma and patients with NLR >= 5 had a worse survival.
      Median PFS of patients with NLR <5 was 5.62 months and in patients with NLR >= 5
      was 3.25 months (p = 0.098), and OS was 11.1 versus 5.6 months for patients with
      NLR<5 and NLR >= 5, respectively (p = 0.017). During the chemotherapy treatment,
      patients who normalized NLR after one cycle presented better outcomes (OS 8.7 vs.
      4.3 months, p = 0.001, for patients who normalized NLR and for patients who
      remained persistently elevated). After multivariate analysis, histology and NLR
      remained independent predictors of survival (p < 0.05). CONCLUSION: In our
      analysis, elevated NLR is a predictor of shorter survival in patients with
      advanced NSCLC and the variation of NLR during the first cycle of treatment
      predicts survival. NLR is an easily measured, reproducible test that could be
      considered to be incorporated in the routine practice in NSCLC patients.

PMID- 22855162
TI  - Pilot study on workload estimate in breast cancer, lung cancer and colorectal
      cancer in a Medical Oncology Service at Valme hospital.
AB  - New advances in the diagnosis and treatment of cancer and the increased incidence
      and prevalence of this disease have led to an increase in the number and duration
      of visits in Medical Oncology in the last few years. Based on the functions of a
      medical oncologist and the time recommended for each work activity established by
      the Spanish Society of Medical Oncology (SEOM), we carried out a pilot study on
      the three most frequent neoplasias in our country [breast cancer (BC), lung
      cancer (LC) and colorectal cancer (CRC)], in order to determine the real time
      each patient requires from a physician and thus establish a recommendation on the
      number of medical oncologists necessary. Using the actual itinerary of the first
      20 patients of 2009 in each of the three neoplasias seen at the Medical Oncology
      Service of the Virgen de Valme University Hospital, we measured the number of
      visits, the antineoplastic treatments received, the number of hospital admissions
      and average length of stay. During the years following the study, these data were
      estimated based on the natural history of each neoplasia. During the first year,
      the average time spent by the medical oncologist was 235, 390 and 265 min on each
      outpatient with BC, LC and CRC, respectively. In hospitalisation, the average
      oncologist/patient minutes were 40, 360 and 118 for BC, LC and CRC, respectively.
      Finally, the time spent on each visit or day of hospitalisation was that
      recommended by the SEOM, achieving an ultimate ratio of 1 oncologist for every 83
      first visits.

PMID- 22855163
TI  - The multimodal management of locally advanced N2 non-small cell lung cancer: is
      there a role for surgical resection? A single institution's experience.
AB  - BACKGROUND: The management of operable locally advanced N2 non-small cell lung
      cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is
      considered the standard of care for inoperable or unresectable patients, but the
      role of trimodality treatment remains controversial. We present our institution's
      experience with the management of stage III (N2) NSCLC patients, analyzing
      whether the addition of surgery improves survival when compared with definitive
      CT-RT alone. METHODS: From 1996 to 2006, 72 N2 NSCLC patients were treated.
      Thirty-four patients received cisplatin-based induction chemotherapy, followed by
      paclitaxel-cisplatin CT-RT, and 38 patients underwent surgery preceded by
      induction and/or followed by adjuvant therapy. Survival curves were estimated by
      Kaplan-Meier analysis, and the differences were assessed with the log-rank test.
      RESULTS: Most of the patients (87 %) were men. The median age was 59 years. A
      statistically significant association between T3-T4c and definitive CT-RT as well
      as between T1-T2c and surgery was noted (p < 0.0001). After a median follow-up
      period of 35 months, the median overall survival (OS) was 42 months for the
      surgery group versus 41 months for the CT-RT patients (p = 0.590). The median
      progression-free survival (PFS) was 14 months after surgery and 25 months after
      CT-RT (p = 0.933). Responders to radical CT-RT had a better OS than non
      responders (43 vs. 17 months, respectively, p = 0.011). No significant
      differences were found in the OS or PFS between the pN0 [14 (37.8 %) patients]
      and non-pN0 patients at thoracotomy. Three treatment-related deaths (7.8 %) were
      observed in the surgical cohort and none in the CT-RT group. CONCLUSIONS: The
      addition of surgery did not render a median OS or PFS benefit when compared with
      CT-RT alone in our series of stage III-N2 NSCLC patients, in accordance with
      previously published data. However, responses to CT-RT had a greater impact in
      terms of OS and PFS. Although the patients selected for management including
      surgery showed a favorable T clinical staging in comparison to patients
      exclusively treated with definitive CT-RT, similar survival outcomes were found.

PMID- 22855164
TI  - Characteristics and long-term survival of colorectal cancer patients aged 44
      years and younger.
AB  - BACKGROUND: This study was to investigate the clinicopathologic characteristics
      and prognosis of colorectal cancer (CRC) patients aged 44 years and younger.
      METHODS: Patients were identified from a prospectively maintained CRC database
      and divided into two groups by age: younger and older group (<=44 and >44 years).
      Clinicopathologic characteristics and postoperative outcomes were compared.
      RESULTS: There were 530 patients aged <=44 years at diagnosis. More patients in
      the younger group had a family history of CRC compared with older patients.
      Younger patients were more likely than older patients to have larger tumours,
      infiltrative growth type tumours, poorly differentiated tumours, mucinous and
      signet-ring cell adenocarcinoma, and advanced TNM stages. Compared to older
      patients, more younger patients received chemotherapy and died of cancer-related
      causes. Overall survival, disease-free survival and cancer-specific survival of
      younger patients were comparable to older patients. Blood transfusion, TNM stage,
      histological grade and disease recurrence were independently associated with
      survival in the younger group. CONCLUSIONS: Despite younger patients having
      unfavourable clinicopathologic features, younger age at diagnosis of CRC appears
      to be associated with similar oncologic outcomes as compared to older patients.

PMID- 22855166
TI  - Is obesity always a risk factor for all breast cancer patients? c-erbB2
      expression is significantly lower in obese patients with early stage breast
      cancer.
AB  - OBJECTIVES: The purpose of this study was to evaluate the relationship between
      body mass index and lipid profiles with breast cancer prognosis together with the
      relationship of these parametres with known breast cancer prognostic indices
      including c-erbB2 expression. PATIENTS AND METHODS: Four hundred and thirty-three
      patients diagnosed with breast cancer at Ankara University, Faculty of Medicine,
      Department of Medical Oncology made up the study population. The primary
      endpoints were relapse and death. Body mass index at the time of diagnosis, lipid
      levels at the time of diagnosis, estrogen receptor status, progesterone receptor
      status, c-erbB2 expression, tumor grade, patient age, axillary lymph node
      involvement level, tumor stage, menopausal status and surgery details were taken
      into account. RESULTS: The mean body mass indices were similar in the remission,
      relapse and mortality groups. Patients with body mass indices higher than 30
      kg/m2 had a lower incidence of c-erbB2 expression when compared to patients with
      body mass indices < 18.5 kg/m(2) (19 vs. 50 %, p = 0.009). Survival analysis
      revealed that patients with body mass indices < 18.5 kg/m(2) had significantly
      shorter disease free survivals when compared to patients with body mass indices
      between 25 and 29.9 kg/m(2). Mean serum lipid levels were similar in the
      remission, relapse and mortality groups. A trend toward relapse was shown in
      patients with total cholesterol > 240 mg/dl, but this was statistically
      insignificant. Survival analysis revealed that patients with triglyceride levels
      lower than 150 mg/dl had a statistically significant longer disease-free survival
      when compared to the other groups. Again a trend towards shorter overall survival
      was seen in patients with total cholesterol > 240 mg/dl, but this relationship
      was also statistically insignificant. CONCLUSION: Most large previous studies
      reported adverse breast cancer outcome with obesity. However in our study,
      patients with lower body weight had a shorter disease-free survival. This could
      be explained by the low number of patients in this study, genetic profile of the
      patient population, possible weight changes after treatment and the inverse
      relationship between body mass index and c-erbB2 expression.

PMID- 22855165
TI  - miRNAs as biomarkers in prostate cancer.
AB  - Current prostate cancer (PCa) diagnosis is based in the serum prostate-specific
      antigen biomarker and digital rectal examination. However, these methods are
      limited by a low predictive value (24-37 %) and a high risk of mistaken results.
      During last years, new promising biomarkers such as Prostate Cancer Antigen 3
      (PCA-3) and TMPRSS2-ETS fusion genes have been evaluated for their clinical use.
      However, the search of new biomarkers that could be used for PCa diagnosis and
      prognosis is still needed. Recent studies have demonstrated that the aberrant
      expression of microRNAs (miRNAs), small non-coding RNAs that negatively regulate
      gene expression, is related with the development of several cancers, including
      PCa. Since miRNAs serve as phenotypic signatures of different cancers, they
      appear as potential diagnostic, prognostic and therapeutic tools. Here, we review
      the current knowledge of miRNA expression patterns in PCa and their role in PCa
      prognosis and therapeutics.

PMID- 22855167
TI  - Helicobacter pylori infection of the larynx may be an emerging risk factor for
      laryngeal squamous cell carcinoma.
AB  - INTRODUCTION: Several studies have implicated Helicobacter pylori as a risk
      factor in laryngeal cancer, but other studies disagree. It is fundamental that
      the relationship between Helicobacter pylori and laryngeal cancer be verified in
      order to provide evidence of ways to prevent the initiation and development of
      this carcinoma. MATERIALS AND METHODS: In total, 81 patients with laryngeal
      squamous cell carcinoma and 75 control subjects were enrolled in a case-control
      study. Semi-nested polymerase chain reaction techniques were applied to detect
      Helicobacter pylori in the laryngeal mucosa and enzyme-linked immunosorbent
      assays were used to detect serum antibodies against Helicobacter pylori. Risk
      factors associated with laryngeal carcinoma were analyzed using logistic
      regression models. RESULTS: The presence of Helicobacter pylori in the larynx was
      higher in patients with laryngeal cancer than in control subjects (71.6 vs. 25.3
      %, p < 0.001). Among patients with laryngeal carcinoma, rates of Helicobacter
      pylori infection were higher in normal laryngeal tissues than in tumor tissues.
      After adjusting for confounding factors, regression analysis indicated that the
      microbe was an independent risk factor for laryngeal cancer (OR = 7.15, 95 % CI
      [3.29, 15.53], p < 0.001). CONCLUSIONS: This study suggests that Helicobacter
      pylori is present in the mucosa of the larynx. The microorganism may be an
      independent risk factor for laryngeal squamous cell carcinoma. The laryngeal
      mucosa thus provides a reservoir for the bacteria possibly, and is a likely
      staging place for its transmission to other areas.

PMID- 22855168
TI  - Clinical importance of phosphatase of regenerating liver-3 expression in breast
      cancer.
AB  - BACKGROUND: Several biomarkers have been previously studied for breast cancer to
      define risk of recurrence and metastasis. Phosphatase of regenerating liver-3
      (PRL-3) is one of them. High PRL-3 expression has been found to be correlated
      with axillary lymph node metastasis and survival in breast cancer. Herein, we
      evaluated the prognostic significance of PRL-3 expression and the relationship
      between PRL-3 and other clinicopathological factors. METHODS: PRL-3 expression
      was analyzed immunohistochemically in 122 invasive breast cancer tissues. We
      evaluated the correlation between PRL-3 and other clinicopathological factors by
      chi2 test. Kaplan-Meier test and log rank method were used to define prognostic
      importance of PRL-3 expression. RESULTS: Of 122 breast cancer tumor samples, 46
      (37.7 %) were negative while 76 (62.3 %) were positive in respect to PRL-3
      expression. There was significant correlation between PRL-3 expression and other
      clinicopathological factors, such as histology, lymphovascular invasion (LVI),
      necrosis, progesterone receptor (PR) status, and the presence of triple negative
      disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared
      to tumors without LVI or necrosis (P = 0.05 and 0.03, respectively). Triple
      negative and cerb-B overexpressed breast cancers were found to be more positive
      PRL-3 expression than hormone receptor positive with cerb-B negative groups
      (luminal A) (P = 0.02).We could not find any relationship between PRL-3
      expression and overall survival (OS) or disease-free survival (DFS) (P > 0.05).
      CONCLUSION: Although PRL-3 expression was related to LVI or necrosis which is
      important for tumor invasiveness, we could not find that PRL-3 as an important
      prognostic factor in breast cancer patients. In addition, triple negative and
      cerb-B overexpressed tumors, which had worse prognosis compared to hormone
      receptor positive without cerb-B expressed group, associated with also PRL-3
      positivity more than PRL-3 negative group.

PMID- 22855169
TI  - Efficiency and mechanism of intracellular paclitaxel delivery by novel
      nanopolymer-based tumor-targeted delivery system, Nanoxel(TM).
AB  - INTRODUCTION: An increasing research interest has been directed toward
      nanoparticle-based drug delivery systems for their advantages. The appropriate
      amalgamation of pH sensitivity and tumor targeting is a promising strategy to
      fabricate drug delivery systems with high efficiency, high selectivity and low
      toxicity. MATERIALS AND METHODS: A novel pH sensitive Cremophor-free paclitaxel
      formulation, Nanoxel(TM), was developed in which the drug is delivered as
      nanomicelles using a polymeric carrier that specifically targets tumors. The
      efficiency and mechanism of intracellular paclitaxel delivery by Nanoxel(TM) was
      compared with two other commercially available paclitaxel formulations:
      Abraxane(TM) and Intaxel(TM), using different cell lines representing target
      cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission
      electron microscopy and quantitative intracellular paclitaxel measurements by
      high performance liquid chromatography. RESULTS: The data obtained from the
      present study revealed that the uptake of nanoparticle-based formulations
      Nanoxel(TM) and Abraxane(TM) is mediated by the process of endocytosis and the
      uptake of paclitaxel was remarkably superior to Intaxel(TM) in all cell lines
      tested. Moreover, the intracellular uptake of paclitaxel in Nanoxel(TM)- and
      Abraxane(TM)-treated groups was comparable. Hence, the nanoparticle-based
      formulations of paclitaxel (Nanoxel(TM) and Abraxane(TM)) are endowed with higher
      efficiency to deliver the drug to target cells as compared to the conventional
      Cremophor-based formulation. CONCLUSION: Nanoxel(TM) appears to be of great
      promise in tumor targeting and may provide an advantage for paclitaxel delivery
      into cancer cells.

PMID- 22855170
TI  - Tumor bed segmentation: first step for partial breast irradiation.
AB  - INTRODUCTION: In breast IMRT simultaneous integrated boost (SIB) treatment and
      accelerated partial breast irradiation (APBI), proper delineation of the tumor
      bed is necessary. Conservative oncoplastic surgery causes changes in peritumoral
      breast tissue that complicates locating the site of the tumor. Nevertheless,
      there are still centers that do not use surgical clips to delineate the site.
      This study aims to show how the lack of clips affects the techniques of SIB and
      APBI in terms of dose distribution and safety margins in the tumor bed. MATERIALS
      AND METHODS: On 30 patients, the defining of the tumor bed obtained from the pre
      surgery CT scan to that outlined on the basis of clips on the post-surgery CT was
      compared. Tumor bed deviation from the original tumor site was quantified. In
      addition, the margins to the original tumor site necessary to guarantee the
      coverage of the tumor bed were calculated. RESULTS: Variations were detected in
      the distances between geometric centers of the PTV (minimum 0.5-maximum 3 cm).
      The maximum margin necessary to include the entire tumor bed was 4.5 cm. Lesions
      located in the upper outer quadrant required the widest margins. If margins are
      not added, the tumor bed volume defined with clips will be underdosed.
      CONCLUSIONS: The definition of the tumor bed based on studies before surgery does
      not have the necessary accuracy. Clips need to be placed in the surgical bed to
      identify the changes occurring after the restorative mammoplasty. Without clips,
      SIB and APBI are not safe.

PMID- 22855171
TI  - Multicenter validation of two nomograms to predict non-sentinel node involvement
      in breast cancer.
AB  - INTRODUCTION: Nomograms are used to predict the involvement of non-sentinel nodes
      (nSN) in breast cancer. This study attempts to externally validate two of the
      more commonly used nomograms (MSKCC and Stanford University). MATERIALS AND
      METHODS: Five hundred and one cases of positive SNB with posterior axillary
      lymphadenectomy from 11 Spanish hospitals with widespread experience of the
      technique were studied. In all cases, an estimate of the probability of nSN
      involvement was made using the MSKCC and the Stanford University nomograms.
      Discrimination was assessed by calculating the area under the receiver operating
      characteristic curve. To assess the calibration of the nomogram, observed
      probability was plotted against the nomogram-calculated predicted probability.
      RESULTS: The overall predictive accuracy of the MSKCC nomogram was 0.684 (95 %
      confidence interval, 0.635-0.732), while in the case of that from Stanford the
      predictive accuracy was 0.658 (95 % confidence interval 0.607-0.709). The mean
      predicted probability of nSN metastases in each group of patients was correlated
      with the observed probability with an acceptable concordance (r = 0.820; p <
      0.004 in MSKCC nomogram and r = 0.888; p < 0.001 in Stanford nomogram).
      CONCLUSION: These nomograms can be useful tools in the evaluation of patients
      with breast cancer and positive sentinel nodes but other factors, including a
      comprehensive clinical assessment, must be used to decide the most appropriate
      surgical approach for an individual patient, especially with regard to avoiding
      unnecessary lymphadenectomy.

PMID- 22855172
TI  - Intraperitoneal bevacizumab combined with cytoreductive surgery: a pre-clinical
      study of tolerance and pharmacokinetics in an animal model.
AB  - INTRODUCTION: Cytoreductive Surgery (CRS) combined with Hyperthermic
      Intraperitoneal Chemotherapy (HIPEC) is currently the only potentially curative
      treatment for peritoneal carcinomatosis (PC). Systemic administration of
      bevacizumab improves survival in patients with metastatic colorectal or ovarian
      cancer. Intraperitoneal administration of bevacizumab has been shown to be safe
      and effective in treating malignant ascites. The combination of CRS with
      intraperitoneal (IP) bevacizumab could maximize local control and survival from
      PC, but the associated morbidity from this is unknown. The aim of this study was
      to evaluate the safety of the combination of CRS with IP bevacizumab and to
      determine the pharmacokinetics of the drug in a rabbit model. METHODS: Twenty
      healthy rabbits underwent a standardized procedure of debulking surgery,
      including peritonectomy and gastrointestinal anastomosis and were randomized to
      receive IP bevacizumab (25 mg/kg) or placebo. Another group of three rabbits
      underwent an instillation of IP bevacizumab (25 mg/kg) without surgery. RESULTS:
      One rabbit that received IP bevacizumab died with no complication associated with
      the use of bevacizumab at autopsy. There was no significant difference between IP
      bevacizumab and placebo in weight loss, length of surgery or morbidity. The
      plasma concentration of bevacizumab increased to a peak at 24 h post IP
      administration. Bevacizumab was not detected in the plasma of animals without
      surgery. CONCLUSION: This study suggests that IP bevacizumab does not increase
      morbidity and mortality of debulking surgery in an animal model. When surgery is
      performed, the pharmacokinetics of IP bevacizumab are modified in plasma.

PMID- 22855173
TI  - EGFR expression is linked to osteopontin and Nf-kappaB signaling in clear cell
      renal cell carcinoma.
AB  - AIM AND BACKGROUND: Epidermal growth factor receptor (EGFR) is a receptor
      tyrosine kinase involved in many important aspects of cell biology that are
      related to tumorigenesis. There are opposite evidences of the role of EGFR in
      renal cancer and the outcome of EGFR-targeted therapies, suggesting the
      complexity of EGFR signaling pathways. In vitro, osteopontin (OPN) and nuclear
      factor kappa B (NF-kappaB) are thought to be involved in specific ligand
      independent EGFR activation that could have a role in resistance to EGFR mAb
      therapy. Aim of this study was to analyze the relationship between EGFR and OPN
      at the protein and mRNA level, as well as their relation to NF-kappaB in clear
      cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: Expression of EGFR,
      OPN, and p65 NF-kappaB protein was analyzed using immunohistochemistry and
      compared mutually in 88 CCRCC samples. Expression of EGFR and OPN mRNAs was
      analyzed using quantitative Real-time PCR in 22 CCRCC samples and compared
      mutually and with NF-kappaB protein expression. RESULTS: Epidermal growth factor
      receptor mRNA level was higher in CCRCC samples in comparison with normal renal
      tissue (p = 0.012) and was associated with high OPN mRNA level, and with NF
      kappaB activation (p < 0.001 and p = 0.045, respectively). Immunohistochemical
      staining showed the inverse association; high EGFR protein expression was related
      with low OPN and NF-kappaB protein expression (p < 0.001 and p = 0.047,
      respectively). CONCLUSION: Epidermal growth factor receptor gene is upregulated
      in CRCC and associated with OPN gene expression and NF-kB signaling. The inverse
      relation between OPN and EGFR at the protein level could probably reflect dynamic
      changes that EGFR undergoes following activation.

PMID- 22855174
TI  - Functional and biologic metrics for predicting radiation pneumonitis in locally
      advanced non-small cell lung cancer patients treated with chemoradiotherapy.
AB  - OBJECTIVE: To study the predictive value of functional and biologic metrics for
      predicting radiation pneumonitis (RP) in locally advanced non-small cell lung
      cancer (LANSCLC) patients treated with chemoradiotherapy. METHODS: Between March
      2006 and April 2010, 57 LANSCLC patients were enrolled in a prospective study.
      Fusion of SPECT and computed tomography scans provides perfusion-weighted
      functional dose-volume histogram (DVH) and associated functional dosimetric
      parameters. Blood for serum biomarkers-interleukin-6 (IL-6), transforming growth
      factor-beta1, and superoxide dismutase (SOD)-was drawn pre-RT and then 40 Gy/4
      weeks during the treatment. The incidence of RP was related to the functional and
      biologic metrics. The predictability of predictors was calculated and compared
      based on the area under receiver-operating characteristic (ROC) curve (AUC).
      RESULTS: Relative volumes of functional lung receiving more than a threshold dose
      of 5-50 Gy at increments of 5 Gy and elevated levels of serum SOD after delivery
      of 40 Gy/4 weeks were associated with RP (p < 0.05). The best predictive efficacy
      of SOD was observed for a cutoff value of 56 U/ml, with a sensitivity of 0.80 (95
      % CI 0.28-0.99) and a specificity of 0.67 (95 % CI 0.43-0.65) (p = 0.040).
      Functional DVH provided better predictive outcome (AUC 0.76-0.98) than standard
      DVH (AUC 0.62-0.86) for patients with poor baseline lung function. CONCLUSION:
      Functional metrics were identified to be better predictors for RP in patients
      with poor baseline lung function. SOD seemed to be a potential predictor for RP;
      however, it will need to be further verified using a larger sample size.

PMID- 22855175
TI  - CD44+/CD24- breast cancer cells isolated from MCF-7 cultures exhibit enhanced
      angiogenic properties.
AB  - BACKGROUND: Recent studies suggest that the relationship between cancer stem
      cells (CSCs) and the vascular niche may be bidirectional; the niche can support
      the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the
      niche. There is little knowledge concerning the role of breast cancer stem cells
      in promoting tumor angiogenesis. AIM: For human breast cancers, CSCs have been
      shown to be associated with a CD44+/CD24- phenotype. We investigated the
      potential activities of CD44+/CD24- breast cancer stem cells in promoting tumor
      angiogenesis. METHODS: The expression of pro-angiogenic genes was determined by
      quantitative real-time RT-PCR. Endothelial cell migration assays were employed to
      evaluate effects of conditioned media from CD44+/CD24- on human umbilical vein
      endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the
      potential of CD44+/CD24- cells to promote angiogenesis. RESULTS: In our study,
      CD44+/CD24- cells expressed elevated levels of pro-angiogenic factors compared
      with CD44+/CD24+ cells. CD44+/CD24- cell-conditioned media significantly
      increased endothelial cell migration. Breast cancer cell lines enriched with
      CD44+/CD24- cells were more pro-angiogenic in the CAM assay than those lacking a
      CD44+/CD24- subpopulation. CD44+/CD24- cells sorted from MCF-7 cell lines were
      more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF
      concentration was significantly higher in CD44+/CD24- cell-conditioned media than
      in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24-
      cells on endothelial cells was abolished by bevacizumab. CONCLUSION: Our findings
      demonstrate that CD44+/CD24- breast cancer stem cells have substantial pro
      angiogenic potential and activity. This provides new insights to explore in the
      development of targeted therapies.

PMID- 22855176
TI  - Intra-operative electron beam radiotherapy for newly diagnosed and recurrent
      malignant gliomas: feasibility and long-term outcomes.
AB  - INTRODUCTION: Intra-operative electron beam radiotherapy (IOERT) is an
      alternative to dose escalation for the treatment of central nervous system
      tumors. The objective of this study was to describe the feasibility and long-term
      outcomes of IOERT in the treatment of primary and recurrent gliomas. MATERIALS
      AND METHODS: From January 1992 through December 2002, all patients treated with
      IOERT at the Hospital San Francisco de Asis, Madrid/Spain were retrospectively
      reviewed. The selection criteria included patients with superficial tumors, KPS
      >70 % and lesions <6 cm. Irradiation was administered in one section. The
      prescribed dose considered the amount of post-resection residual tumor, previous
      radiotherapy and the tolerance level of brain structures exposed to IOERT.
      RESULTS: There were 17 patients (53 %) with newly diagnosed malignant brain
      gliomas and 15 patients with recurrent tumors. The delivered dose varied from 8
      to 20 Gy (median 12.5 Gy) for primary and from 8 to 16 Gy (median 10 Gy) for
      recurrent tumors. The median overall survival for the entire cohort was 13 months
      (14 and 10.4 months for the primary and recurrent, respectively). Three patients
      presented with radionecrosis, one patient with osteomyelitis at the craniotomy
      bone flap, one with intracerebral hemorrhage, and another patient experienced a
      pulmonary embolism. CONCLUSIONS: IOERT is a feasible technique and can be viewed
      as a tool in the treatment of newly diagnosed or recurrent brain gliomas.

PMID- 22855177
TI  - Daily schedule for high-dose-rate brachytherapy in postoperative treatment of
      endometrial carcinoma.
AB  - PURPOSE: To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on
      local control and toxicity in the postoperative treatment of endometrial
      carcinoma (EC). MATERIALS AND METHODS: From January 2007 to September 2010, 112
      patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48
      IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid
      and 23/112 other types. Radiotherapy patients were divided into two groups-Group
      1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of
      5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy).
      Toxicity evaluation RTOG scores for bladder and rectum, and the objective
      criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and
      Fisher exact tests. RESULTS: With a mean follow-up of 29.52 months (range 9.60
      53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity
      appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1);
      late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in
      vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9
      % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had
      G1-G2 as vaginal scores for late problems. CONCLUSIONS: (1) Daily HDRBT using two
      fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment
      was a safe regime. (2) Group 1 showed a higher incidence of late vaginal
      toxicity.

PMID- 22855178
TI  - Methylation in the p53 promoter in epithelial ovarian cancer.
AB  - OBJECTIVE: Ovarian cancer is a leading cause of death from gynecologic tumors,
      however, the molecular and especially epigenetic events underlying this
      transformation are poorly understood. Promoter methylation status of tumor
      suppressor genes may be associated with transcriptional silencing and tumor
      progression. It has been shown that methylation of CpG dinucleotides located in
      the promoter region of p53 is associated with low expression levels of this gene.
      The aim of this study was to investigate promoter methylation of p53 gene in
      ovarian cancer by comparison with normal ovarian tissue. METHODS: To search for
      promoter methylation of p53 gene we used methylation-specific PCR (MSP) to
      compare the methylation status of 66 tissue samples of ovarian cancer with 37
      control samples. RESULTS: In our study methylation specific PCR revealed p53
      promoter methylation in 34 of 66 (51.5 %) of specimens with ovarian cancer.
      CONCLUSION: These results indicate that methylation in p53 promoter region may
      play an important role in carcinogenesis of ovarian cancer and could potentially
      be used in screening of ovarian cancer, and may have implications for future
      chemotherapy based on epigenetic changes.

PMID- 22855179
TI  - Retreatment with radiotherapy for symptomatic bone, brain or visceral metastases.
AB  - BACKGROUND: The need for reirradiation in the metastatic disease appears when
      other modalities of treatment lose their efficacy. The aim of reirradiation in
      the metastatic disease is mainly palliative to control a particular symptom.
      However, this theoretical benefit must be confronted against the risk of an
      undesirable toxicity. MATERIALS AND METHODS: Experience with reirradiation for
      symptomatic bone, brain or visceral metastases are reviewed. Twenty-two patients
      were found to have a second palliative radiotherapy on the same location.
      Location of metastases were visceral in 5 (23 %) patients, brain in 4 (18 %)
      patients, spine in 1 (4.5 %) patient and bone metastasis other than spine in 12
      (54.5 %) patients. Median dose delivered in the first treatment was 30 Gy (range
      20-30 Gy) and 20 Gy for the second treatment (range 6-32.4 Gy). RESULTS: A good
      symptomatic response after first irradiation (complete response or disappearance
      of >50 % of symptoms) was reached in 21 (95.5 %) of the 22 patients analyzed.
      After second irradiation, 82 % (18 patients) achieved a good response, 3 (14 %)
      patients had a moderate response (relief of symptoms <50 %) whereas no response
      was observed in 1 (4 %) patient. Acute toxicity was limited to grade 1-2
      proctitis in 2 and 3 patients after the first and second irradiation,
      respectively. No cases of late toxicity after the first or second irradiation
      were recorded. CONCLUSION: A second treatment with palliative radiotherapy is
      feasible and well tolerated and offers the possibility of symptomatic relief in a
      high percentage of patients with symptomatic metastases.

PMID- 22855180
TI  - Human adipose tissue from normal and tumoral breast regulates the behavior of
      mammary epithelial cells.
AB  - INTRODUCTION: Stromal-epithelial interactions mediate both breast development and
      breast cancer progression. In the present work, we evaluated the effects of
      conditioned media (CMs) of human adipose tissue explants from normal (hATN) and
      tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases
      activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast
      epithelial cell lines. MATERIALS AND METHODS: Human adipose tissues were obtained
      from patients and the conditioned medium from hATN and hATT collected after 24 h
      of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs
      and proliferation and adhesion, as well as migration ability and metalloprotease
      activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs
      were quantified. The statistical significance between different experimental
      conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed.
      RESULTS: Tumor and non-tumor breast epithelial cells significantly increased
      their proliferation activity after 24 h of treatment with hATT-CMs compared to
      control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was
      significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to
      induce significantly lower expression or less activity of the components involved
      in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and
      MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to
      hATN-CMs. CONCLUSIONS: We conclude that the microenvironment of the tumor
      interacts in a dynamic way with the mutated epithelium. This evidence leads to
      the possibility to modify the tumor behavior/phenotype through the regulation or
      modification of its microenvironment. We developed a model in which we obtained
      CMs from adipose tissue explants completely, either from normal or tumor breast.
      In this way, we studied the contribution of soluble factors independently of the
      possible effects of direct cell contact.

PMID- 22855181
TI  - Quantitative analysis of EZH2 expression and its correlations with lung cancer
      patients' clinical pathological characteristics.
AB  - INTRODUCTION: Elevated Enhancer of Zeste Homologue 2 (EZH2) expression is
      involved in many human malignancies through epigenetically silencing related
      genes. However, the study of the EZH2 protein expression in lung cancer remains
      at the qualitative or semi-quantitative level. The present study is to elucidate
      the roles of EZH2 in the progression and metastasis of different subtypes of lung
      cancer at quantitative level. MATERIALS AND METHODS: Lung carcinoma tissue
      microarray was constructed containing 32 normal adult lung tissues, 113 lung
      carcinomas and 57 lymph-node metastases. EZH2 protein expression was detected by
      immunohistochemistry and assessed quantitatively with Leica Q500MC image analysis
      system. Positive unit (PU) value was used to evaluate the protein expression
      intensity of positive cells from systematically selected fields under the
      microscope. RESULTS: Elevated Enhancer of Zeste Homologue 2 PU in lung carcinomas
      was significantly greater than that in normal lung tissues (p = 0.001). Increased
      EZH2 expression was correlated with histological subtypes, differentiation, TNM
      stage, and lymph-node metastases (p < 0.05). EZH2 PU of primary lung carcinomas
      was smaller than that of lymph-node metastasis (p = 0.002). EZH2 PU was not
      associated with patients' gender, age, smoking status, tumor location, and tumor
      size (p > 0.05). CONCLUSIONS: Elevated Enhancer of Zeste Homologue 2 PU is
      increased with the development of lung cancer. EZH2 may play an important role in
      the progression and metastasis of lung cancer.

PMID- 22855182
TI  - Development and characterization of an isogenic cell line with a radioresistant
      phenotype.
AB  - INTRODUCTION: Radiation resistance is a major cause of death in cancer patients.
      Cancer cells react during radiotherapy by re-programming specific cell functions
      that may confer resistance to radiation. The understanding of this complex
      process is hindered due to the lack of appropriate study models. We describe an
      experimental development of a radioresistant isogenic cancer cell line, and its
      molecular characterization. MATERIALS AND METHODS: A431-cultured cells were
      irradiated for 7 month until 85 Gy. Then, a selected single cell was left to grow
      as stable A431-R cell line. Clonogenic assay was used to determine cell survival,
      the alpha and beta parameters of the LQ model, and the mean inactivation dose.
      The DNA repair ability of cells was evaluated by pulsed-field electrophoresis
      method. Differential effect of fractionated radiation was ultimately tested in
      xenografts. Furthermore, we used a wound healing assay, Western blot for EGFR,
      AKT and ERK1/2 and ELISA test for vascular endothelial growth factor (VEGF)
      secretion. Finally we explored CD44 marker and cell cycle distribution. RESULTS:
      The established A431-R cell line showed radiation resistance in clonogenic
      assays, repair of radiation-induced DNA fragmentation and xenografted tumours.
      The radiation resistance was associated with in vitro higher cell growth and
      migration, increased levels of former oncoproteins, and secretion of VEGF.
      CONCLUSIONS: In this model, the emergence of radiation resistance was associated
      with the acquisition of biological traits that support more aggressive behaviour
      of cancer cells. We have generated a model that will be useful for mechanistic
      studies and development of rational treatments against radiation resistance in
      cancer.

PMID- 22855183
TI  - Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma.
AB  - AIM: Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play
      an important role in the development of human gliomas. However, their prognostic
      values are not clear. The aim of this study was to investigate whether co
      expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas.
      METHODS: Immunohistochemistry and western blot were used to investigate the
      expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. RESULTS:
      The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both
      significantly higher (both P < 0.001) than those in non-neoplastic brain tissues
      according to the immunohistochemistry analysis, which was confirmed by the
      western blot analysis. Additionally, the overexpression of either MMP-14 or MMP
      19 was significantly associated with the advanced WHO grade (both P = 0.02), the
      low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the
      poor overall survival (both P = 0.01). Moreover, the Multivariate Cox
      proportional-hazards regression analysis revealed that the increased expressions
      of MMP-14 and MMP-19 were both independent prognostic factors for poor overall
      survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was
      additively and more significantly (P = 0.006) associated with adverse prognosis
      in patients with gliomas than respective expression of MMP-14 and MMP-19.
      CONCLUSIONS: These findings indicated for the first time that the co-expression
      of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma
      patients, suggesting that the co-expression of these proteins may be used as both
      an early diagnostic and independent prognostic marker.

PMID- 22855184
TI  - Ultrasound-assisted endocavitary HDR-Ir(192) brachytherapy for unresectable
      locally advanced uterine cervix carcinoma: retrospective analysis focusing the
      efficacy and tolerability.
AB  - PURPOSE: To evaluate the impact of uterine cavity's ultrasound to final selected
      length of intracavitary tandem. The efficacy and tolerability of external beam
      radiation plus HDR-Ir(192) brachytherapy in our cohort of patients were also
      estimated. MATERIALS AND METHODS: 48 women with locally advanced unresectable
      uterine cervix carcinoma were treated by HDR-Ir(192) endocavitary brachytherapy
      between January 2007 and January 2009. The median age was 63 (range 38-74). The
      distribution according to Federation of Gynaecology and Obstetrics (FIGO) staging
      system was as follows: Stage IIB, 54.16 %; IIIA, 10.4 %; IIIB, 27.0 %; and IVA,
      8.3 %. HDR intracavitary brachytherapy was given weekly, beginning at the last
      week of whole pelvis irradiation, with a dose of 7 Gy to point A for three to
      four fractions. The median overall treatment time was 50 days (range 42-73 days).
      The median follow-up time was 2.7 years (range 3 months to 4.9 years).
      Multivariate analysis was performed using the Cox regression proportional hazards
      model. RESULTS: The complete remission rate after radiotherapy was 93.75 %
      (45/48). The 5-year actuarial major complication rates (Grade 3 or above) were
      6.3 % overall (2.1 % proctitis, 2.1 % cystitis and 2.1 % enteritis). Estimation
      of the length of uterine cavity by ultrasound helped decisively in the proper
      placement of the intrauterine tandem inserted. CONCLUSIONS: Prior knowledge of
      the length of uterine cavity can facilitate the decisions regarding the proper
      insertion length of the tandem. Results of cervical cancer treatment with
      external beam radiation and HDR intracavitary brachytherapy in our hospital are
      encouraging.

PMID- 22855185
TI  - Decreased expression of chromodomain helicase DNA-binding protein 5 is an
      unfavorable prognostic marker in patients with primary gallbladder carcinoma.
AB  - AIM: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal
      neural development and in tumorigenesis of various human cancers. However, its
      role in primary gallbladder carcinoma (PGC) is still unclear. The aim of this
      study was to investigate CHD5 expression in PGC and its clinical significance.
      METHODS: CHD5 mRNA and protein expression in 120 PGC and 20 normal gallbladder
      specimens was determined by quantitative reverse transcription-polymerase chain
      reaction (QRT-PCR) and Western blotting analysis, respectively. RESULTS: The
      expression levels of CHD5 mRNA and protein in PGC tissues were both significantly
      lower than those in the normal epithelium of the gallbladder (mRNA: P = 0.006;
      protein: P = 0.01). CHD5 mRNA expression was closely correlated with its protein
      expression (r = 0.8; P < 0.001). Additionally, the low expression of CHD5 protein
      was significantly associated with high pathologic T stage (P = 0.01) and clinical
      stage (P = 0.008), and advanced histologic grade (P = 0.009). The expression
      levels of CHD5 protein in PGC tissues with positive nodal metastasis were also
      significantly lower than those without (P = 0.01). Survival analysis showed that
      low CHD5 expression was associated with shorter disease-free (P = 0.01) and
      overall survival (P = 0.008) compared to those with high CHD5 expression in PGC
      patients. Furthermore, multivariate analyses showed that the decreased expression
      of CHD5 was an independent prognostic marker for both unfavorable disease-free (P
      = 0.01) and overall survival (P = 0.006). CONCLUSION: CHD5 may be involved in
      carcinogenesis of PGC and its down-regulation may be significantly correlated
      with unfavorable clinicopathologic features including poor overall and disease
      free survival in patients.

PMID- 22855187
TI  - Promises and pitfalls of new technology in radiotherapy.

PMID- 22855186
TI  - Identification of valid reference housekeeping genes for gene expression analysis
      in tumor neovascularization studies.
AB  - INTRODUCTION: Real time RT-PCR is a widely used technique to evaluate and confirm
      gene expression data obtained in different cell systems and experimental
      conditions. However, there are many conflicting reports about the same gene or
      sets of gene expression. A common method is to report the interest gene
      expression relative to an internal control, usually a housekeeping gene (HKG),
      which should be constant in cells independently of experimental conditions.
      MATERIALS AND METHODS: In this study, the expression stability of ten HKGs was
      considered in parallel in two cell systems (endothelial and osteosarcoma cells):
      beta actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), TATA box
      binding protein (TBP), hypoxanthine phosphoribosyl-transferase 1 (HPRT1),
      Cyclophilin A (PPIA), beta-2-microglobulin (B2M), glucuronidase beta (GUSB),
      eukaryotic translation elongation factor 1 alpha1 (EEF1A1), transferrin receptor
      (TFRC), ribosomal protein S18 (RPS18). In order to study the stability of
      candidate reference genes, data have been also analyzed by several algorithms
      (geNorm, NormFinder, BestKeeper and delta-Ct method). RESULTS AND CONCLUSIONS:
      The overall analysis obtained by the comprehensive ranking showed that RPS18 and
      PPIA are appropriate internal reference genes for tumor neovascularization
      studies where it is necessary to analyze both systems at the same time.

PMID- 22855188
TI  - A high body mass index is not a worse prognostic factor for endometrial carcinoma
      in a predominantly obese population.
AB  - AIM: We investigate if body mass index (BMI, kg * m(2)) is related to clinical
      pathological characteristics in primary tumor and disease outcome in endometrial
      cancer. BACKGROUND: Endometrial cancer incidence is increasing in industrialized
      countries. High BMI is associated with worse prognosis for many diseases.
      INTRODUCTION: Endometrial carcinoma is the most common gynecological malignancy
      in industrialized countries and the incidence has been increasing over the last
      few decades associated with obesity, however, it is not clear if a high BMI is
      associated with poor prognosis. PATIENTS AND METHODS: In total, 147 women
      primarily treated for endometrial carcinoma at the Instituto Nacional de
      Cancerologia during 2000-2005 were studied. Body mass index was available for all
      patients and related to comprehensive clinical and histopathological data.
      RESULTS: High BMI was related to endometrioid histology and low/intermediate
      grade, and overweight/obese women had the same survival as the normal/underweight
      women. In survival analysis adjusting for age, histological subtype and grade,
      BMI showed no independent prognostic impact. CONCLUSION: High BMI was
      significantly associated with markers of non-aggressive disease and women with
      high BMI had the same survival time in univariate analysis.

PMID- 22855189
TI  - Hypofractionated helical tomotherapy using 2.5-2.6 Gy daily fractions for
      localized prostate cancer.
AB  - BACKGROUND: The purpose of this study is to evaluate the tolerability of
      hypofractionated helical tomotherapy (HT) in the treatment of localized prostate
      cancer. MATERIALS AND METHODS: We evaluated 48 patients with primary
      adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with
      hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens
      included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at
      2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored
      using the Radiation Therapy Oncology Group scoring system. RESULTS: Thirty-two
      patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy.
      The median age at diagnosis was 69 years (range 49-87) and the median follow-up
      11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %).
      No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU
      toxicities occurred in 19 and 6 % of patients, respectively. The incidence of
      late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher
      late toxicities were observed. Multivariate analysis showed that patients treated
      at 2.6 Gy/fraction or those who received a total radiation dose >=70 Gy had
      higher rates of grade >=2 acute GU toxicity (P = 0.004 and P = 0.048,
      respectively). CONCLUSION: Hypofractionated HT in the treatment of localized
      prostate cancer is well tolerated with no grade 3 or higher early or late GI and
      GU toxicities. Further research is needed to assess definitive late toxicity and
      tumor control.

PMID- 22855190
TI  - Serum VEGF and VEGF-C values before surgery and after postoperative treatment in
      gastric cancer.
AB  - INTRODUCTION: Angiogenesis and lymphangiogenesis are essential processes for the
      formation of blood and lymphatic vessels that allow tumour growth and spread. The
      binding of VEGF and VEGF-C factors with their receptors (VEGFR2, VEGFR3) in
      endothelial cells triggers signals that regulate these processes. We compared
      preoperative serum VEGF and VEGF-C levels with samples obtained after completion
      of surgery and adjuvant treatment in patients with gastric cancer. In addition,
      we determined the prognostic value and relationship to survival of serum VEGF and
      VEGF-C levels. METHODS: We used a prospective cohort study of 59 gastric cancer
      patients who underwent surgery. Serum VEGF and VEGF-C were measured by enzyme
      linked immunosorbent assay (ELISA) the day before surgery and 6 months later,
      after completion of adjuvant treatment. RESULTS: Serum VEGF values decreased
      after treatment in patients with resectable tumours (mean +/- SD) (405.42 +/-
      298.38 vs. 306.38 +/- 212.47 pg/ml; p < 0.01), poorly differentiated and
      undifferentiated tumours (G3, G4) (438 +/- 339.71 vs. 322.47 +/- 210.71 pg/ml; p
      = 0.01), locally advanced gastric tumours (T4 stage) (424.27 +/- 323.08 vs.
      333.62 +/- 221.72 pg/ml; p = 0.03) and tumours with a greater number of involved
      regional lymph nodes (N3) (442.38 +/- 311.52 vs. 337.4 +/- 203.64 pg/ml; p =
      0.04). Serum preoperative VEGF values over 761 pg/ml were associated with shorter
      patient survival. The mean overall survival time for patients with serum VEGF
      levels higher than 761 pg/ml was 7 +/- 2.99 months (95 % CI 1.14-12.86) while for
      patients with serum VEGF levels of less than 761 pg/ml was 21.18 +/- 2.88 (95 %
      CI 15.54-26.83) The mean disease-specific survival time for patients with serum
      VEGF levels higher than 761 pg/ml was 6.25 +/- 2.53 months (95 % CI 1.29-11.21)
      while for patients with serum VEGF levels of less than 761 pg/ml was 27.57 +/-
      3.45 (95 % CI 20.80-34.35). Multivariate analysis identified preoperative serum
      VEGF levels as an independent prognostic factor (HR = 0.144; p = 0.03).
      CONCLUSIONS: Serum VEGF levels decreased after the completion of treatment in
      patients with resected tumours, suggesting VEGF tracking may be useful in
      monitoring progression. Preoperative measurement of serum VEGF may help us
      identify patients with a poor prognosis.

PMID- 22855191
TI  - Effectiveness of oxaliplatin desensitization protocols.
AB  - INTRODUCTION: Hypersensitivity reaction (HSR) to antineoplastic drugs can force
      doctors to stop treatment and seek other alternatives. These alternatives may be
      less effective, not as well tolerated and/or more expensive. Another option is to
      use desensitization protocols that induce a temporary state of tolerance by
      gradually administering small quantities of the antineoplastic drug until the
      therapeutic dosage is reached. The aim of this study is to assess the
      effectiveness of oxaliplatin desensitization protocols. MATERIALS AND METHODS: A
      retrospective observational study was carried out between January 2006 and May
      2011. The inclusion criteria were patients undergoing chemotherapy treatment with
      oxaliplatin who had developed an HSR to the drug and who were candidates for
      continuing the treatment using a desensitization protocol. The patients' clinical
      records were reviewed and variables were gathered relating to the patient, the
      treatment, the HSR, and the desensitization protocol administered. The data were
      analysed using version 18.0 of the statistics program SPSS. RESULTS: A total of
      53 desensitization protocols were administered to 21 patients. In 89 % of these
      cases, no new reactions occurred while the drug was being administered. New
      reactions of mild severity only occurred in 11 % of cases, and none of these
      reactions were severe enough for treatment to be stopped. All patients were able
      to complete the desensitization protocol. CONCLUSION: This study confirms that
      oxaliplatin desensitization protocols are safe and effective and allow patients
      to continue with the treatment that initially caused an HSR.

PMID- 22855192
TI  - Comments to SEOM clinical guidelines for the treatment of thyroid cancer.

PMID- 22855193
TI  - IMRT: preliminary results in a series of advanced head-and-neck cancer patients.
AB  - PURPOSE: To determine retrospectively 2-3 year local and regional control (LRC),
      free-of-disease survival (FDS) and overall survival (OS), as well as summarized
      toxicities in a group of 31 advanced head-and-neck cancer patients, treated at
      our institution between 2004 and 2011 with definitive IMRT low-dose concomitant
      boost, the majority of them with concurrent chemotherapy based on cisplatin. The
      results are also shown in the sub-group of nasopharyngeal cancer patients (NPC:
      15 cases). PATIENTS AND METHODS: Radiological basal and contrasted CT series, MR
      CT or PET/CT fused images in the setup position with immobilization mask were
      registered in simulation therapy patients. Planed doses were: 70 Gy in primary
      tumor and positive nodes >1 cm; 63 Gy in high-risk areas of microscopic diseases
      +10 mm safety margin; and 56 Gy in low risk of diseases regional lymph nodes.
      Treatment was delivered using a Varian 2100 Clinac with sliding windows IMRT.
      Spinal cord doses were limited to a strict maximum of 45 Gy, and optimization
      aimed for mean doses in parotid glands below 26 Gy, especially in the
      contralateral parotid gland. Online DRR-portal X-ray comparison images were taken
      every day with a deviation module tolerance <=3 mm. RESULTS: The mean follow-up
      since IMRT was 34 months (interval: 8-89; median 31 months). Median follow-up in
      living patients was 22 months. The 2-year rate for global LRC was 64 %, for FDS
      61 % and OS 77 %. For the NPC group after 2 years, LRC was 73 %, FDS 73 % and OS
      93 %. The 3-year rates were similar. Seven patients died as a consequence of
      local and/or regional progression (mean time 10 months). Relapses were observed
      in eight patients (26 %), but only seven could be confirmed by biopsy (22.6 %;
      mean time to relapse: 8.6 months). Global acute mucositis was 61 % and chronic
      mucositis was shown in six cases which developed xerostomia (19 %) in the first
      control after IMRT, but 1 year later it was reduced to only four patients, two
      Grade 2 and two Grade 1. CONCLUSIONS: No excessive, unwarranted toxicities were
      observed using concomitant low doses boost in IMRT. High rates of compliance to
      concurrent chemotherapy were achieved. Late xerostomia associated with this
      regime decreased 1 year after conclusion of treatment. The implementation of IMRT
      requires advances in imaging for better tumor delineation; otherwise the
      physician loses the advantage of dose modulation or faces a risk of geographical
      miss.

PMID- 22855194
TI  - Therapeutic nanosystems for oncology nanomedicine.
AB  - Cancer is a complex disease which includes many pathologies featuring abnormal
      growth of healthy cells, invasion and metastization. Cellular uncontrolled growth
      increases the amount of abnormal cells, these cells reach the blood stream and
      other healthy tissues giving rise to secondary tumors. Even though great
      progresses have been made in understanding cancer aetiology and in the
      development of new anticancer drugs, cancer still remains one of the leading
      causes of death worldwide. Most common cancers include breast cancer, lung
      cancer, colorectal cancer and brain cancer. Conventional chemotherapeutics have
      proven to be inefficient in cancer treatment due to lack of specificity and poor
      drug accumulation in tumors. In addition, they cause severe side effects.
      Available treatments must be prolonged on time to achieve some therapeutic
      effect; however, this often leads to the development of multidrug resistance by
      tumor cells. Nanotechnology platforms are, therefore, being exploited as
      potential alternatives. Nanosystems have been reported to target and deliver the
      drug in situ to selectively kill cancer cells, decreasing toxicity on healthy
      organs and tissues as well as side effects. Furthermore, some nanosystems have
      been reported to overcome tumor resistance, at least to some extent. Over the
      years several nanosystems have been proposed to diagnose and treat cancers, such
      as dendrimers, polymeric micelles, superparamagnetic iron oxide cores, gold
      nanoparticles, liposomes and other lipid nanoparticles. Due to their small size
      and biocompatibility, they can reach the target site without being detected by
      the immune system and suffer cellular uptake or deliver the drug in the tumor
      vicinity.

PMID- 22855195
TI  - Practice patterns in the management of prostate cancer in Spain: results from a
      national survey among radiation oncologists in 2009.
AB  - INTRODUCTION: Little is known of practice patterns on advanced prostate cancer
      (PC) in Spain. The study objectives were to investigate practice patterns in the
      management of PC and to determine the adherence to the 2007 Spanish guidelines
      for the management of PC. MATERIALS AND METHODS: An epidemiological, cross
      sectional study was undertaken. Study-specific questionnaires were distributed to
      all centers with radiation oncology (RO) facilities delivering megavoltage
      radiation therapy (RT) in Spain (n = 108). A questionnaire evaluated diagnostic
      and treatment approaches to PC in low-risk and high-risk cases. And a 12-item
      questionnaire was used to assess guidelines adherence. RESULTS: Responses were
      obtained from 102 centers (94.0 % response rate). In the high-risk scenario, the
      majority of clinicians (99.0 %) chose combined modality treatment with RT and
      androgen deprivation (AD) and 93.0 % recommended long-term AD. External-beam RT
      (EBRT) doses ranging 72-76 Gy were used in 59.5 % of centers and >76 Gy was
      employed in 40.5 %. In the low-risk scenario, EBRT was chosen by 59.6 %,
      brachytherapy by 39.4 %, and active surveillance by 1 %. The consensus was high
      (score 5 + 4 >= 90 %) on 8/12 questions assessing adherence to guidelines, being
      high specifically on items related to RT technique, RT dose, combination of HT
      and RT in intermediate/high-risk patients, and prognostic factors. CONCLUSIONS:
      This is the largest survey to date of Spanish RO departments dealing with PC. The
      study results therefore likely provide a highly reliable picture of clinical
      practice in Spain in this century and show how this practice is influenced by
      clinical evidence from randomized trials and consensus conferences.

PMID- 22855196
TI  - Multicenter phase II clinical trial of preoperative capecitabine with concurrent
      radiotherapy in patients with locally advanced rectal cancer.
AB  - INTRODUCTION: To assess pathologic complete response, sphincter preservation
      rates and toxicity profile of preoperative chemoradiation with capecitabine in
      resectable locally advanced rectal cancer. MATERIALS AND METHODS: Fifty-eight
      patients from six Spanish centers were included (March 2004 to June 2005) with
      histological/cytological diagnosis of locally advanced rectal cancer, age between
      18 and 80 years, ECOG 0-2, adequate bone marrow, renal and hepatic functions.
      Prior chemotherapy/radiotherapy was not allowed. Preoperative treatment was
      capecitabine 825 mg/m(2) bid concomitant to radiotherapy (45 + 5.4 Gy boost over
      5.5 weeks). Surgery was performed 4-8 weeks after completion of
      chemoradiotherapy. RESULTS: Fifty-eight patients were enrolled in this study:
      60.3 % males, median age of 64.5 (30.9-78.7) years, 28.6 % with ECOG 0 and 71.4 %
      with ECOG 1. Median distance of tumor from the anal verge was 7 (1-12) cm. Fifty
      two (89.6. %) patients completed preoperative chemoradiotherapy. Primary tumor
      and node downstaging occurred in 61.1 and 69.6 % of patients, respectively.
      Surgery was performed in 55 patients (94.8 %): 80 % had negative lymph nodes and
      72.7 % underwent sphincter-preserving procedures. A pathologic complete response
      was observed in 10.5 % (95 % CI 2.5-18.5) of the patients. Main grade I-II
      toxicities were leucopenia (43.1 %), neutropenia (24.1 %), anemia (36.2 %),
      diarrhea (32.8 %) and skin disorders (5.1 %), from which diarrhea (6.9 %),
      leucopenia (1.7 %) and skin disorders (1.7 %) reached grade III. There were no
      grade IV toxicities. CONCLUSIONS: Preoperative capecitabine-based chemoradiation
      is a well-tolerated and effective neoadjuvant treatment for locally advanced
      rectal cancer that achieves encouraging rates of tumor downstaging.

PMID- 22855197
TI  - Impact of radiotherapy delay on survival in glioblastoma.
AB  - BACKGROUND: Previous studies in glioblastoma have concluded that there is no
      decrease in survival with increasing time to initiation of RT up to 6 weeks after
      surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6
      weeks is not small in some countries. The aim of our study was to evaluate the
      effect of RT delay beyond 6 weeks on survival of patients who have undergone
      completed resection of a glioblastoma. METHODS: We reviewed 107 consecutive
      glioblastoma patients who had a complete surgical resection at our hospital.
      Clinical data, including delay in initiation of RT, were prospectively collected.
      The impact of single parameters on overall survival was determined by univariate
      and multivariate analyses. RESULTS: According to univariate analysis, variables
      that had a prognostic influence on survival were age (p = 0.036), KPS (p =
      0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before
      42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance
      scale, additional treatment with chemotherapy, and initiation of RT before 6
      weeks after surgery were favorable, independent prognostic factors of survival.
      CONCLUSIONS: Survival is significantly reduced in glioblastoma patients if RT is
      not initiated within the 6 weeks after complete resection of the tumor.

PMID- 22855205
TI  - Understanding dietary monitoring and self-weighing by gastric bypass patients: a
      pilot study of self-monitoring behaviors and long-term weight outcomes.
AB  - BACKGROUND: Weight and dietary monitoring have been associated with better weight
      loss outcomes among dieters using lifestyle modification, but they have rarely
      been studied among gastric bypass surgery patients. This exploratory study
      examined dietary and weight self-monitoring behaviors and their association with
      weight outcomes in a sample of gastric bypass patients who were at least 12
      months post-surgery. METHODS: A convenience sample of 32 female and 5 male
      patients living in Upstate New York was recruited through support group list
      servs. The participants completed an anonymous on-line survey about their weight
      histories, surgical histories, current weights, dietary monitoring practices,
      weight monitoring practices, and demographic characteristics. Measures were
      developed to assess frequency of monitoring behaviors (recording food intake,
      mentally tracking food, weighing/measuring foods, and self-weighing). Weight loss
      outcomes, based on self-reported weights, were current body mass index (BMI),
      percent excess BMI lost, and percent weight loss maintained. RESULTS: Mean pre
      surgical BMI was 49.5 +/- 6.6. The participants were at an average of 32 months
      post-surgery with a BMI 31.2 +/- 6.6. They maintained 89.2 +/- 14.1% of their
      weight loss and 76.3 +/- 26.0% excess BMI was lost. Higher scores for dietary
      monitoring behaviors, being unmarried, and lower pre-surgery BMI were associated
      with lower current BMI and greater excess BMI lost when controlling for age, sex,
      and time since surgery. CONCLUSIONS: This study yielded constructs, measures, and
      relationships that warrant further examination in a larger sample of gastric
      bypass patients.

PMID- 22855199
TI  - Changes in calcitropic hormones, bone markers and insulin-like growth factor I
      (IGF-I) during pregnancy and postpartum: a controlled cohort study.
AB  - Pregnancy and lactation cause major changes in calcium homeostasis and bone
      metabolism. This population-based cohort study presents the physiological changes
      in biochemical indices of calcium homeostasis and bone metabolism during
      pregnancy and lactation INTRODUCTION: We describe physiological changes in
      calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy
      and lactation. METHODS: We studied 153 women planning pregnancy (n=92 conceived)
      and 52 non-pregnant, age-matched female controls. Samples were collected prior to
      pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls
      were followed in parallel. RESULTS: P-estradiol (E2), prolactin and 1,25
      dihydroxyvitamin D (1,25(OH)2D) increased (p<0.001) during pregnancy, whereas
      plasma levels of parathyroid hormone (P-PTH) and calcitonin decreased (p<0.01).
      Insulin-like growth factor I (IGF-I) was suppressed (p<0.05) in early pregnancy
      but peaked in the third trimester. Postpartum, E2 was low (p<0.05); prolactin
      decreased according to lactation status (p<0.05). 1,25(OH)2D was normal and IGF-I
      was again reduced (p<0.05). P-PTH and calcitonin increased postpartum. From early
      pregnancy, markers of bone resorption and formation rose and fall, respectively
      (p<0.001). From the third trimester, bone formation markers increased in
      association with IGF-I changes (p<0.01). Postpartum increases in bone turnover
      markers were associated with lactation status (p<0.001). During lactation, plasma
      phosphate was increased, whereas calcium levels tended to be decreased which may
      stimulate PTH levels during and after prolonged lactation. CONCLUSION: The
      increased calcium requirements in early pregnancy are not completely offset by
      increased intestinal calcium absorption caused by high 1,25(OH)2D since changes
      in bone markers indicated a negative bone balance. The rise in bone formation in
      late pregnancy may be initiated by a spike in IGF-I levels. The high bone
      turnover in lactating women may be related to high prolactin and PTH levels, low
      E2 levels and perhaps increased parathyroid hormone-related protein levels.

PMID- 22855206
TI  - The effect of acute taurine ingestion on 3-km running performance in trained
      middle-distance runners.
AB  - Limited research examining the effect of taurine (TA) ingestion on human exercise
      performance exists. The aim of this study was to investigate the effect of acute
      ingestion of 1,000 mg of TA on maximal 3-km time trial (3KTT) performance in
      trained middle-distance runners (MDR). Eight male MDR (mean +/- SD: age 19.9 +/-
      1.2 years, body mass 69.4 +/- 6.6 kg, height 180.5 +/- 7.5 cm, 800 m personal
      best time 121.0 +/- 5.3 s) completed TA and placebo (PL) trials 1 week apart in a
      double-blind, randomised, crossover designed study. Participants consumed TA or
      PL in capsule form on arrival at the laboratory followed by a 2-h ingestion
      period. At the end of the ingestion period, participants commenced a maximal
      simulated 3KTT on a treadmill. Capillary blood lactate was measured pre- and post
      3KTT. Expired gas, heart rate (HR), ratings of perceived exertion (RPE), and
      split times were measured at 500-m intervals during the 3KTT. Ingestion of TA
      significantly improved 3KTT performance (TA 646.6 +/- 52.8 s and PL 658.5 +/-
      58.2 s) (p = 0.013) equating to a 1.7 % improvement (range 0.34-4.24 %). Relative
      oxygen uptake, HR, RPE and blood lactate did not differ between conditions (p =
      0.803, 0.364, 0.760 and 0.302, respectively). Magnitude-based inference results
      assessing the likeliness of a beneficial influence of TA were 99.3 %. However,
      the mechanism responsible for this improved performance is unclear. TA's
      potential influence on exercise metabolism may involve interaction with the
      muscle membrane, the coordination or the force production capability of involved
      muscles. Further research employing more invasive techniques may elucidate TA's
      role in improving maximal endurance performance.

PMID- 22855207
TI  - Human relaxin-2: historical perspectives and role in cancer biology.
AB  - One of the most recognised and studied family of peptide hormones is the insulin
      superfamily. Within this family is the relaxin subfamily which comprises seven
      members: relaxin-1, -2 and -3 and insulin-like peptides 3, 4, 5 and 6. Besides
      exhibiting sequence similarities, each member exists as an active A-B heterodimer
      linked by three disulfide bonds. This mini-review is divided into three broad
      themes: an overview of all insulin superfamily members (including structural
      similarities); roles of each superfamily member and finally, a focus on the
      pleiotropic peptide hormone, human relaxin-2. In addition to promoting
      vasodilatory effects leading to evaluation in Phase III clinical trials for the
      treatment of acute heart failure, relaxin has recently been shown to be highly
      expressed by cancer cells, aiding in their proliferation, invasiveness and
      metastasis. These contrary effects of relaxin are discussed together with current
      efforts in the development of relaxin antagonists that may possess future
      therapeutic potential for the treatment of certain cancers.

PMID- 22855208
TI  - Characterization of the aqueous iron(III) chelation chemistry of a potential
      Trojan Horse antimicrobial agent: chelate structure, stability and pH dependent
      speciation.
AB  - The aqueous solution equilibria of a beta-lactam antimicrobial agent containing a
      3-hydroxy, 4-pyridinone group (L (PF)) binding to Fe(III) in aqueous solution has
      been characterized through spectrophotometric and potentiometric titrations. The
      metal-free ligand has four observable protonation constants, pK(a1) = 2.6, pK(a2)
      = 3.43, pK(a3) = 6.43, and pK(a4) = 9.62. L (PF) forms a 3:1 ligand:Fe(III)
      complex in aqueous solution through coordinate-covalent bond formation
      exclusively involving the bidentate hydroxypyridinone moiety. This 3:1 L (PF):Fe
      complex was found to have a stability constant of log beta(130) = 33.46. A
      speciation diagram for the L (PF) system demonstrates that in the region of
      physiological pH the tris-(L (PF))Fe(III) complex, Fe(L(PF)) (3) (6-) ,
      predominates. This complex exhibits two irreversible reduction waves in solution
      at -30 mV versus NHE, corresponding to a ligand-based reduction, and at -385 mV
      versus NHE, corresponding to an irreversible Fe(3+)/Fe(2+) reduction of the
      Fe(L(PF)) (3) (6-) complex.

PMID- 22855209
TI  - Reconstitution, spectroscopy, and redox properties of the photosynthetic
      recombinant cytochrome b(559) from higher plants.
AB  - A study of the in vitro reconstitution of sugar beet cytochrome b(559) of the
      photosystem II is described. Both alpha and beta cytochrome subunits were first
      cloned and expressed in Escherichia coli. In vitro reconstitution of this
      cytochrome was carried out with partially purified recombinant subunits from
      inclusion bodies. Reconstitution with commercial heme of both (alphaalpha) and
      (betabeta) homodimers and (alphabeta) heterodimer was possible, the latter being
      more efficient. The absorption spectra of these reconstituted samples were
      similar to that of the native heterodimer cytochrome b(559) form. As shown by
      electron paramagnetic resonance and potentiometry, most of the reconstituted
      cytochrome corresponded to a low spin form with a midpoint redox potential +36
      mV, similar to that from the native purified cytochrome b(559). Furthermore,
      during the expression of sugar beet and Synechocystis sp. PCC 6803 cytochrome
      b(559) subunits, part of the protein subunits were incorporated into the host
      bacterial inner membrane, but only in the case of the beta subunit from the
      cyanobacterium the formation of a cytochrome b(559)-like structure with the
      bacterial endogenous heme was observed. The reason for that surprising result is
      unknown. This in vivo formed (betabeta) homodimer cytochrome b(559)-like
      structure showed similar absorption and electron paramagnetic resonance spectral
      properties as the native purified cytochrome b(559). A higher midpoint redox
      potential (+126 mV) was detected in the in vivo formed protein compared to the in
      vitro reconstituted form, most likely due to a more hydrophobic environment
      imposed by the lipid membrane surrounding the heme.

PMID- 22855210
TI  - Treatment use and costs among privately insured youths with diagnoses of bipolar
      disorder.
AB  - OBJECTIVE: Recent evidence suggests that children are increasingly diagnosed as
      having bipolar disorder, yet no studies have quantified treatment costs for
      pediatric patients. The objectives of the study were to identify one-year health
      services utilization and treatment costs among youths newly diagnosed as having
      bipolar disorder. METHODS: MarketScan administrative claims from 2005 to 2007
      were used to construct a retrospective person-level cohort of children ages zero
      to 17 to identify one-year health services utilization and costs among privately
      insured youths with a bipolar diagnosis. Inpatient and outpatient services were
      categorized as mental health related or non-mental health related. Pharmacy costs
      were classified as psychotropic or nonpsychotropic. RESULTS: In the sample (4,973
      youths), one-year mean reimbursements for health services were $10,372, and
      patient out-of-pocket spending was $1,429 per child. Mental health services
      accounted for 71% of all health care spending, with psychotropic medications and
      inpatient care contributing the largest proportions of total spending (24% and
      27%, respectively) . CONCLUSIONS: The costs of care among privately insured
      children with bipolar disorder are similar to those of adults. However, spending
      on children is concentrated on mental health-related services. Because private
      insurance plans have historically limited mental health service benefits, the
      concentration of spending on mental health services may place a greater burden on
      families for out-of-pocket payments. As mental health parity is adopted by
      private insurers, monitoring its impact on patient utilization and costs of
      health services will be important, particularly for children with serious mental
      illness.

PMID- 22855211
TI  - Measures of phylogenetic differentiation provide robust and complementary
      insights into microbial communities.
AB  - High-throughput sequencing techniques have made large-scale spatial and temporal
      surveys of microbial communities routine. Gaining insight into microbial
      diversity requires methods for effectively analyzing and visualizing these
      extensive data sets. Phylogenetic beta-diversity measures address this challenge
      by allowing the relationship between large numbers of environmental samples to be
      explored using standard multivariate analysis techniques. Despite the success and
      widespread use of phylogenetic beta-diversity measures, an extensive comparative
      analysis of these measures has not been performed. Here, we compare 39 measures
      of phylogenetic beta diversity in order to establish the relative similarity of
      these measures along with key properties and performance characteristics. While
      many measures are highly correlated, those commonly used within microbial ecology
      were found to be distinct from those popular within classical ecology, and from
      the recently recommended Gower and Canberra measures. Many of the measures are
      surprisingly robust to different rootings of the gene tree, the choice of
      similarity threshold used to define operational taxonomic units, and the presence
      of outlying basal lineages. Measures differ considerably in their sensitivity to
      rare organisms, and the effectiveness of measures can vary substantially under
      alternative models of differentiation. Consequently, the depth of sequencing
      required to reveal underlying patterns of relationships between environmental
      samples depends on the selected measure. Our results demonstrate that using
      complementary measures of phylogenetic beta diversity can further our
      understanding of how communities are phylogenetically differentiated. Open-source
      software implementing the phylogenetic beta-diversity measures evaluated in this
      manuscript is available at http://kiwi.cs.dal.ca/Software/ExpressBetaDiversity.

PMID- 22855212
TI  - Significant and persistent impact of timber harvesting on soil microbial
      communities in Northern coniferous forests.
AB  - Forest ecosystems have integral roles in climate stability, biodiversity and
      economic development. Soil stewardship is essential for sustainable forest
      management. Organic matter (OM) removal and soil compaction are key disturbances
      associated with forest harvesting, but their impacts on forest ecosystems are not
      well understood. Because microbiological processes regulate soil ecology and
      biogeochemistry, microbial community structure might serve as indicator of forest
      ecosystem status, revealing changes in nutrient and energy flow patterns before
      they have irreversible effects on long-term soil productivity. We applied
      massively parallel pyrosequencing of over 4.6 million ribosomal marker sequences
      to assess the impact of OM removal and soil compaction on bacterial and fungal
      communities in a field experiment replicated at six forest sites in British
      Columbia, Canada. More than a decade after harvesting, diversity and structure of
      soil bacterial and fungal communities remained significantly altered by
      harvesting disturbances, with individual taxonomic groups responding
      differentially to varied levels of the disturbances. Plant symbionts, like
      ectomycorrhizal fungi, and saprobic taxa, such as ascomycetes and actinomycetes,
      were among the most sensitive to harvesting disturbances. Given their significant
      ecological roles in forest development, the fate of these taxa might be critical
      for sustainability of forest ecosystems. Although abundant bacterial populations
      were ubiquitous, abundant fungal populations often revealed a patchy
      distribution, consistent with their higher sensitivity to the examined soil
      disturbances. These results establish a comprehensive inventory of bacterial and
      fungal community composition in northern coniferous forests and demonstrate the
      long-term response of their structure to key disturbances associated with forest
      harvesting.

PMID- 22855213
TI  - Biogeography of Rhizobium radiobacter and distribution of associated temperate
      phages in deep subseafloor sediments.
AB  - Bacteriophages might be the main 'predators' in the marine deep subsurface and
      probably have a major impact on indigenous microbial communities. To identify
      their function within this habitat, we have determined their abundance and
      distribution along the sediment columns of two continental margin and two open
      ocean sites that were recovered during Leg 201 of the Ocean Drilling Program. For
      all investigated sites, viral abundance followed the total cell numbers with a
      virus-to-cell ratio between 1 and 10 in the upper 100 mbsf (meters below
      seafloor). An increasing ratio of about 20 in deeper layers indicated an ongoing
      viral production in up to 11 Ma old sediments. We have used Rhizobium radiobacter
      as the most frequently isolated organism from the deep subsurface with a high in
      situ abundance to identify the frequency of associated rhizobiophages. In this
      study, 16S rRNA gene copies of R. radiobacter accounted for up to 5.6% of total
      bacterial 16S rRNA genes (average: 0.75%) as detected by quantitative PCR. A
      distinctive distribution was identified for R. radiobacter as indicated by a site
      specific arrangement of genetically similar populations. Whole genome information
      of rhizobiophage RR1-A was used to generate a primer system for quantitative PCR
      specifically targeting the prophage antirepressor gene, indicative for temperate
      phages. The quantification of this gene within various sediment horizons showed a
      contribution of temperate phages of up to 14.3% to the total viral abundance.
      Thus, the high amount of temperate phages within the sediments and among all
      investigated isolates indicates that lysogeny is the main viral proliferation
      mode in deep subsurface populations.

PMID- 22855214
TI  - Single-incision laparoscopic cholecystectomy versus conventional laparoscopic
      cholecystectomy: meta-analysis and systematic review of randomized controlled
      trials.
AB  - BACKGROUND: The objective of this study was to analyze systematically the
      randomized, controlled trials that compared single-incision laparoscopic
      cholecystectomy (SILC) and conventional laparoscopic cholecystectomy (CLC).
      METHODS: The meta-analysis was conducted according to the Quality of Reporting of
      Meta-analysis (QUORUM) standards. The included studies were analyzed
      systematically using the statistical software package RevMan. The summated
      outcomes were expressed as the risk ratios (RR) for dichotomous variables and
      standardized mean differences (SMD) for continuous variables. RESULTS: Eleven
      randomized trials encompassing 858 patients were retrieved from the electronic
      databases. In the random effects model, postoperative pain, postoperative
      complications, length of hospital stay, cosmesis score, conversion rate, and time
      to return to normal activities were statistically comparable between the two
      cholecystectomy techniques. SILC was associated with a longer operating time [SMD
      0.71; 95 % confidence interval (CI) 0.38, 1.05; z = 4.18; p < 0.0001) and an
      increased requirement for additional port insertion (RR 6.54; 95 % CI 2.19,
      19.57; z = 3.36; p < 0008). However, there was significant heterogeneity among
      the trials. CONCLUSIONS: SILC does not offer any advantage over CLC for treating
      benign gallbladder disorders. CLC may be used assiduously for this purpose.

PMID- 22855215
TI  - High risk of biliary fistula after isolated segment VIII liver resection.
AB  - BACKGROUND: For tumors deeply located in segment VIII (S8), right hepatectomy
      (RH) often is thought to solve the issue of technical accessibility. Yet, the
      common existence of an associated underlying diseased liver raises the question
      of parenchymal-sparing resection. METHODS: From 2002 to 2011, 34 patients
      underwent isolated S8 resection, and their operative and postoperative
      characteristics were compared to 34 matched patients who underwent RH for lesions
      located in S8. RESULTS: Indications and preoperative characteristics were
      comparable between the two groups except for larger tumors in RH patients
      compared with S8 patients (48 vs. 40 mm; p = 0.001). Achieving S8 resection
      required significantly longer clamping time (45 vs. 37 min, p = 0.011), more
      additional biliostasis because of obvious biliary leak (65 vs. 18 %, p < 0.001),
      and subsequently increased application of sealant material (56 vs. 9 %, p <
      0.001) compared with RH. The overall complication rate was similar between the
      two groups (59 vs. 62 %, p = 0.804), although a trend toward a higher rate of
      biliary fistula was observed in S8 patients (20 vs. 6 %, p = 0.07). Routine CT
      scan performed on postoperative day 7 found significantly more subphrenic
      collections in S8 patients compared with RH patients (53 vs. 9 %, p = 0.003). On
      pathological examination, surgical margin width was comparable between the two
      groups. CONCLUSIONS: Anatomical S8 resection remains a technically demanding
      procedure with an elevated risk of postoperative biliary fistula but allows
      achieving adequate carcinologic resection. Increasing consideration for
      parenchymal sparing resection should lead to favor this approach as a treatment
      of choice for small and medium-sized tumors located in this segment.

PMID- 22855216
TI  - Early detection of hypocalcemia after total/completion thyroidectomy: routinely
      usable algorithm based on serum calcium level.
AB  - BACKGROUND: The purpose of this prospective bicentric study was to investigate
      the course of serum calcium (Ca) and phosphorus (Phph) after total/completion
      thyroidectomy to establish a reliable and cost-effective strategic algorithm to
      detect patients at risk for postoperative hypocalcemia. METHODS: This
      observational study included 136 patients. Serum Ca and Phph levels were
      preoperatively and postoperatively recorded 6, 12, 20, and 48 h (H) after skin
      closure. Criteria for hypocalcemia were postoperative Ca levels <=1.9 mmol/L at
      any time point and/or patients experiencing symptoms of hypocalcemia.
      Postoperative Ca supplementation was never given before H20 assay. Ca levels and
      their differences between time points were compared. RESULTS: Twenty-four percent
      of patients experienced hypocalcemia. At H12 and H20, the rates of patients with
      Ca levels <=1.9 mmol/L were similar and larger than at H6 (p < 0.001). The H20
      preoperative difference had the best area under the ROC curves (value = 0.87),
      and a difference <=-0.3 was significantly more frequent in case of hypocalcemia
      (p = 0.001). The H20 assay and the difference H20-preop were consequently
      selected to design a new algorithm for hypocalcemia detection. Adding H48 assay
      in some specific cases (12.5 % of all included patients) enabled 100 % detection.
      Phosphorus assays were not informative in detecting hypocalcemia. CONCLUSIONS:
      This new algorithm enables, with 100 % sensitivity and 88.4 % specificity, early
      detection of severe hypocalcemia after total/completion thyroidectomy. It may
      become a useful and cost-effective tool for safe and early patient discharge,
      especially if PTH assays cannot be routinely used because of their availability
      or cost.

PMID- 22855217
TI  - Robotic versus conventional laparoscopic surgery for rectal cancer: a cost
      analysis from a single institute in Korea.
AB  - BACKGROUND: Since its introduction, robotic surgery has been applied actively in
      several fields of minimally invasive surgery, and its use in the field of
      colorectal surgery is also increasing. In the studies to date, feasibility and
      safety have been the main focus, but the economics involved are important to
      examine. We compared the economics of robotic surgery with those of laparoscopic
      surgery for rectal cancer. MATERIAL AND METHODS: We analyzed the clinical
      characteristics, total hospital charges, payments, operating room costs, and
      hospital profits for patients who underwent robotic and laparoscopic resection of
      rectal cancer at Korea University Anam Hospital between July 2007 and August
      2010. RESULTS: From July 2007 and August 2010, 154 robot-assisted and 150
      laparoscopic rectal surgeries were performed. The patient demographics were
      similar in the two groups with the exception of tumor location (6.7 vs 8.7 cm
      distal to the anal verge; p = 0.043), preoperative chemoradiotherapy (22.7 vs 8
      %; p = 0.001), and operative time (285.2 vs 219.7 min; p = 0.018). Postoperative
      course and complications were also similar in the two groups. The total hospital
      charges in U.S. dollars ($14,647 vs $9,978; p = 0.001) and payments made by
      patients ($11,540 vs $3,956; p < 0.001) were significantly higher in the robotic
      group. Hospital profit was significantly lower in the robotic group than in the
      laparoscopic group ($689 vs $1,671; p < 0.001). CONCLUSIONS: Robot-assisted
      surgery is more expensive than laparoscopic surgery for rectal cancer.
      Considering that robotic surgery can be applied more easily for low-lying
      cancers, the cost-effectiveness of robotic rectal cancer surgery should be
      assessed based on oncologic outcomes and functional results from future studies.

PMID- 22855218
TI  - Myeloperoxidase levels predict executive function.
AB  - The main purpose of the study was to investigate whether baseline myeloperoxidase
      (MPO) levels are associated with executive cognitive function in individuals with
      high physical activity. Baseline serum MPO levels of 56 elderly marathon runners
      and 58 controls were assessed by ELISA. Standardized tests were applied to survey
      domain-specific cognitive functions. Changes in brain morphology were visualized
      by magnetic resonance imaging (MRI). High baseline serum MPO levels correlated
      with worse outcome in tests assessing executive cognitive function in athletes
      but not in the control group (NAI maze test p<0.05, Trail Making Test ratio
      p<0.01). In control participants, subcortical white matter hyperintensities were
      associated with higher scores on the Geriatric Depression Scale (p<0.05), whereas
      athletes seem to be protected from this effect. During strenuous exercising, MPO
      as well as its educts may be elevated due to increased oxygen intake and
      excretion of pro-inflammatory mediators inducing host tissue damage via oxidative
      stress. This outweighs the potential benefits of physical activity on cognitive
      function.

PMID- 22855219
TI  - Developing an effective arterial stiffness monitoring system using the spring
      constant method and photoplethysmography.
AB  - This study aimed to develop a fast and effective arterial stiffness monitoring
      system for diabetic patients using the spring constant method and
      photoplethysmography (PPG). The experimental group comprised 70 patients (4 type
      1 diabetes mellitus patients and 66 type 2 diabetes mellitus patients); 23
      participants suffered from atherosclerosis. All were subjected to the
      measurements of both the carotid-femoral pulse wave velocity (cfPWV) and the
      spring constants evaluated using the PPG pulse as well as the radial pulse. The
      control group comprised 70 normal participants (39 men and 31 women) who did not
      have diabetes mellitus, with an age range of 40-84 years. All control group
      members were only subjected to the measurement by the spring constant method. For
      the experimental group, statistical analysis indicated a significantly high
      correlation between the spring constants computed using PPG and the radial pulse
      (p < 0.001, correlation coefficient =0.89). The result also showed a significant
      negative correlation between the cfPWV and the spring constant of PPG (p < 0.001,
      correlation coefficient = - 0.72); multivariate analysis similarly indicated a
      close relationship. In addition, we used Student's t test to examine the
      difference between the experimental and control groups for the spring constant of
      PPG. A P value less than 0.05 confirmed that the difference between the two
      groups was statistically significant. In the receiver operating characteristic
      curve, area under curve (=0.82) indicates a good discrimination, and a spring
      constant of PPG below 516 (g/s  (2)) may imply a risk of arterial stiffness for
      diabetic patients. These findings imply that the spring constant of PPG could
      effectively identify normal versus abnormal characteristics of elasticity in
      normal and diabetic participants. As a result of some excellent characteristics
      in clinical monitoring, the spring constant computed using PPG shows the
      effectiveness and feasibility in the monitoring system of arterial stiffness.

PMID- 22855220
TI  - Forecasting depression in bipolar disorder.
AB  - Bipolar disorder is characterized by recurrent episodes of mania and depression
      and affects about 1% of the adult population. The condition can have a major
      impact on an individual's ability to function and is associated with a long-term
      risk of suicide. In this paper, we report on the use of self-rated mood data to
      forecast the next week's depression ratings. The data used in the study have been
      collected using SMS text messaging and comprises one time series of approximately
      weekly mood ratings for each patient. We find a wide variation between series:
      some exhibit a large change in mean over the monitored period and there is a
      variation in correlation structure. Almost half of the time series are forecast
      better by unconditional mean than by persistence. Two methods are employed for
      forecasting: exponential smoothing and Gaussian process regression. Neither
      approach gives an improvement over a persistence baseline. We conclude that the
      depression time series from patients with bipolar disorder are very heterogeneous
      and that this constrains the accuracy of automated mood forecasting across the
      set of patients. However, the dataset is a valuable resource and work remains to
      be done that might result in clinically useful information and tools.

PMID- 22855221
TI  - Gender-specific reference intervals for cord blood leptin in Crete, Greece.
AB  - Cord leptin is a biomarker of fetal growth and adiposity with a role in
      predicting weight gain during the first months of life and childhood obesity. Our
      objective was to calculate gender-specific reference intervals for cord blood
      leptin in healthy neonates in Crete, Greece. We used data from the prospective
      mother-child cohort ("Rhea" study) in Crete, Greece. The analysis included 398
      neonates chosen with strict inclusion criteria based on maternal and fetal
      characteristics. Cord leptin reference intervals for male neonates were 1.4-18.2
      ng/mL and for females 2.0-25.8 ng/mL. Females had higher leptin levels (median
      7.4; IQR 4.7-10.9) compared to males (median 4.9; IQR 3.2-7.6) (p < 0.001).
      Conclusion Gender-specific reference ranges are essential in clinical practice
      for correct interpretation of leptin values in cord blood and early detection of
      childhood obesity.

PMID- 22855226
TI  - Extraction of airways from CT (EXACT'09).
AB  - This paper describes a framework for establishing a reference airway tree
      segmentation, which was used to quantitatively evaluate fifteen different airway
      tree extraction algorithms in a standardized manner. Because of the sheer
      difficulty involved in manually constructing a complete reference standard from
      scratch, we propose to construct the reference using results from all algorithms
      that are to be evaluated. We start by subdividing each segmented airway tree into
      its individual branch segments. Each branch segment is then visually scored by
      trained observers to determine whether or not it is a correctly segmented part of
      the airway tree. Finally, the reference airway trees are constructed by taking
      the union of all correctly extracted branch segments. Fifteen airway tree
      extraction algorithms from different research groups are evaluated on a diverse
      set of twenty chest computed tomography (CT) scans of subjects ranging from
      healthy volunteers to patients with severe pathologies, scanned at different
      sites, with different CT scanner brands, models, and scanning protocols. Three
      performance measures covering different aspects of segmentation quality were
      computed for all participating algorithms. Results from the evaluation showed
      that no single algorithm could extract more than an average of 74% of the total
      length of all branches in the reference standard, indicating substantial
      differences between the algorithms. A fusion scheme that obtained superior
      results is presented, demonstrating that there is complementary information
      provided by the different algorithms and there is still room for further
      improvements in airway segmentation algorithms. 

PMID- 22855228
TI  - Semiautomatic white blood cell segmentation based on multiscale analysis.
AB  - This paper approaches novel methods to segment the nucleus and cytoplasm of white
      blood cells (WBC). This information is the basis to perform higher level tasks
      such as automatic differential counting, which plays an important role in the
      diagnosis of different diseases. We explore the image simplification and contour
      regularization resulting from the application of the Self-Dual Multiscale
      Morphological Toggle (SMMT), an operator with scale-space properties. To segment
      the nucleus, the image preprocessing with SMMT has shown to be essential to
      ensure the accuracy of two well-known image segmentations techniques, namely,
      watershed transform and Level Set methods. To identify the cytoplasm region, we
      propose two different schemes, based on granulometric analysis and on
      morphological transformations. The proposed methods have been successfully
      applied to a large number of images, showing promising segmentation and
      classification results for varying cell appearance and image quality, encouraging
      future works. 

PMID- 22855227
TI  - Hyperbaric oxygen preconditioning protects skin from UV-A damage.
AB  - Hyperbaric oxygen therapy (HBOT) is used for a number of applications, including
      the treatment of diabetic foot ulcers and CO poisoning. However, we and others
      have shown that HBOT can mobilize cellular antioxidant defenses, suggesting that
      it may also be useful under circumstances in which tissue protection from
      oxidative damage is desired. To test the protective properties of hyperbaric
      oxygen (HBO) on a tissue level, we evaluated the ability of a preconditioning
      treatment regimen to protect cutaneous tissue from UV-A-induced oxidative damage.
      Three groups of hairless SKH1-E mice were exposed to UV-A 3 days per week for 22
      weeks, with two of these groups receiving an HBO pretreatment either two or four
      times per week. UV-A exposure increased apoptosis and proliferation of the skin
      tissue, indicating elevated levels of epithelial damage and repair. Pretreatment
      with HBO significantly reduced UV-A-induced apoptosis and proliferation. A
      morphometric analysis of microscopic tissue folds also showed a significant
      increase in skin creasing following UV-A exposure, which was prevented by HBO
      pretreatment. Likewise, skin elasticity was found to be greatest in the group
      treated with HBO four times per week. The effects of HBO were also apparent
      systemically as reductions in caspase-3 activity and expression were observed in
      the liver. Our findings support a protective function of HBO pretreatment from a
      direct oxidative challenge of UV-A to skin tissue. Similar protection of other
      tissues may likewise be achievable.

PMID- 22855229
TI  - Embedded ubiquitous services on hospital information systems.
AB  - A Hospital Information Systems (HIS) have turned a hospital into a gigantic
      computer with huge computational power, huge storage and wired/wireless local
      area network. On the other hand, a modern medical device, such as echograph, is a
      computer system with several functional units connected by an internal network
      named a bus. Therefore, we can embed such a medical device into the HIS by simply
      replacing the bus with the local area network. This paper designed and developed
      two embedded systems, a ubiquitous echograph system and a networked digital
      camera. Evaluations of the developed systems clearly show that the proposed
      approach, embedding existing clinical systems into HIS, drastically changes
      productivity in the clinical field. Once a clinical system becomes a pluggable
      unit for a gigantic computer system, HIS, the combination of multiple embedded
      systems with application software designed under deep consideration about
      clinical processes may lead to the emergence of disruptive innovation in the
      clinical field. 

PMID- 22855230
TI  - Haptic feedback enhances grip force control of sEMG-controlled prosthetic hands
      in targeted reinnervation amputees.
AB  - In this study, we hypothesized that haptic feedback would enhance grip force
      control of surface electromyography (sEMG)-controlled prosthetic hands for
      targeted reinnervation (TR) amputees. A new miniature haptic device, a tactor,
      that can deliver touch, pressure, shear, and temperature sensation, allows
      modality-matching haptic feedback. TR surgery that creates sensory regions on the
      patient's skin that refer to the surface of the missing limb allows somatotopic
      matching haptic feedback. This paper evaluates the hypothesis via an sEMG
      controlled virtual prosthetic arm operated by TR amputees under diverse haptic
      feedback conditions. The results indicate that the grip force control is
      significantly enhanced via the haptic feedback. However, the simultaneous display
      of two haptic channels (pressure and shear) does not enhance, but instead
      degrades, grip force control.

PMID- 22855231
TI  - Classification of traumatic brain injury severity using informed data reduction
      in a series of binary classifier algorithms.
AB  - Assessment of medical disorders is often aided by objective diagnostic tests
      which can lead to early intervention and appropriate treatment. In the case of
      brain dysfunction caused by head injury, there is an urgent need for quantitative
      evaluation methods to aid in acute triage of those subjects who have sustained
      traumatic brain injury (TBI). Current clinical tools to detect mild TBI
      (mTBI/concussion) are limited to subjective reports of symptoms and short
      neurocognitive batteries, offering little objective evidence for clinical
      decisions; or computed tomography (CT) scans, with radiation-risk, that are most
      often negative in mTBI. This paper describes a novel methodology for the
      development of algorithms to provide multi-class classification in a substantial
      population of brain injured subjects, across a broad age range and representative
      subpopulations. The method is based on age-regressed quantitative features
      (linear and nonlinear) extracted from brain electrical activity recorded from a
      limited montage of scalp electrodes. These features are used as input to a unique
      "informed data reduction" method, maximizing confidence of prospective validation
      and minimizing over-fitting. A training set for supervised learning was used,
      including: "normal control," "concussed," and "structural injury/CT positive
      (CT+)." The classifier function separating CT+ from the other groups demonstrated
      a sensitivity of 96% and specificity of 78%; the classifier separating "normal
      controls" from the other groups demonstrated a sensitivity of 81% and specificity
      of 74%, suggesting high utility of such classifiers in acute clinical settings.
      The use of a sequence of classifiers where the desired risk can be stratified
      further supports clinical utility.

PMID- 22855232
TI  - Single-layer skull approximations perform well in transcranial direct current
      stimulation modeling.
AB  - In modeling the effect of transcranial direct current stimulation, the
      representation of the skull is an important factor. In a spherical model, we
      compared a realistic skull modeling approach, in which the skull consisted of
      three isotropic layers, to anisotropic and isotropic single-layer approximations.
      We simulated direct current stimulation for a range of conductivity values and
      investigated differences in the resulting current densities. Our results
      demonstrate that both approximation methods perform well, provided that the
      optimal conductivity values are used. We found that for both the anisotropic and
      the isotropic approximations the optimal conductivity values are largely dictated
      by the equivalent radial conductivity of the three-layered skull.

PMID- 22855233
TI  - Kinematic data analysis for post-stroke patients following bilateral versus
      unilateral rehabilitation with an upper limb wearable robotic system.
AB  - Robot-assisted stroke rehabilitation has become popular as one approach to
      helping patients recover function post-stroke. Robotic rehabilitation requires
      four important elements to match the robot to the patient: realistic
      biomechanical robotic elements, an assistive control scheme enabled through the
      human-robot interface, a task oriented rehabilitation program based on the
      principles of plasticity, and objective assessment tools to monitor change. This
      paper reports on a randomized clinical trial utilizing a complete robot-assisted
      rehabilitation system for the recovery of upper limb function in patients post
      stroke. In this study, a seven degree-of-freedom (DOF) upper limb exoskeleton
      robot (UL-EXO7) is applied in a rehabilitation clinical trial for patients stable
      post-stroke (greater than six months). Patients had a Fugl-Meyer Score between 16
      39, were mentally alert (> 19 on the VA Mini Mental Status Exam) and were between
      27 and 70 years of age. Patients were randomly assigned to three groups:
      bilateral robotic training, unilateral robotic training, and usual care. This
      study is concerned with the changes in kinematics in the two robotic groups. Both
      patient groups played eight therapeutic video games over 12 sessions (90 min, two
      times a week). In each session, patients intensively played the different
      combination of video games that directly interacted with UL-EXO7 under the
      supervision of research assistant. At each session, all of the joint angle data
      was recorded for the evaluation of therapeutic effects. A new assessment metric
      is reported along with conventional metrics. The experimental result shows that
      both groups of patients showed consistent improvement with respect to the
      proposed and conventional metrics.

PMID- 22855234
TI  - Using ultrasound images of the forearm to predict finger positions.
AB  - Medical ultrasound imaging is a well-known technique to gather live views of the
      interior of the human body. It is totally safe, it provides high spatial and
      temporal resolution, and it is nowadays available at any hospital. This suggests
      that it could be used as a human-computer interface. In this paper, we use
      ultrasound images of the human forearm to predict the finger positions, including
      thumb adduction and thumb rotation. Our experimental results show that there is a
      clear linear relationship between the features we extract from the images, and
      finger positions, expressed as angles at the metacarpo-phalangeal joints. The
      method is uniformly valid for all subjects considered. The unavoidable movements
      of the ultrasound probe with respect to the skin and of the skin with respect to
      the inner musculoskeletal structure are compensated for using the optical flow.
      Typical applications of this system range from teleoperated fine manipulation to
      finger stiffness estimation to ergonomy. If successfully applied to transradial
      amputees, it could be also used to reconstruct the imaginary limb, paving the way
      to, e.g., fine control of hand prostheses, treatment of neuropathic/phantom limb
      pain and visualization of the imaginary limb as a tool for the neuroscientist.

PMID- 22855235
TI  - Cyclic alternating patterns in normal sleep and insomnia: structure and content
      differences.
AB  - This work aims to investigate new markers for the quantitative characterization
      of insomnia, in the context of sleep microstructure, as expressed by cyclic
      alternating pattern (CAP) sleep. The study group includes 11 subjects with normal
      sleep and 10 subjects with diagnosed primary insomnia. Differences between normal
      sleepers and insomniacs are investigated, in terms of dynamics and content of CAP
      events. The overall rate of CAP and of different phases is considered. The
      dynamic in the structure and alternation of CAP events is further studied in
      different scales by use of wavelet analysis, and calculation of energy/entropy
      features. The content of CAP events is studied in terms of electroencephalography
      (EEG) complexity analysis for the different types of events. Statistically
      significant differences are highlighted, both in structure and content. Besides
      confirming the increase in CAP rate, main findings regarding the microstructure
      difference in insomnia include: 1) as regards the deep sleep building phases,
      more irregular activation-deactivation patterns, with bigger deactivation time,
      i.e., distance between consecutive activation events, and appearing with higher
      EEG complexity in deactivation, and 2) a bigger duration of desynchronisation
      phases, with increased EEG complexity and more irregular patterns. This analysis
      extends previous findings on the relation between CAPrate increase and sleep
      instability mechanisms, proposing specific features of CAP that seem to play a
      role in insomnia (as consistently presented via classification analysis). This
      opens new perspectives for the understanding of the role of CAP in the
      quantitative characterization of sleep and its disorders.

PMID- 22855236
TI  - Diagnosis and differential diagnosis of Crohn's disease of the ileal pouch.
AB  - Approximately 20%-30% of patients with ulcerative colitis will eventually require
      colectomy despite recent advances in medical therapy. Ileal pouch-anal
      anastomosis has become the surgical treatment of choice. A subset of patients
      with ileal pouches can develop Crohn's disease or a Crohn's-disease-like
      condition of the ileal pouch after surgery. Diagnosis, differential diagnosis,
      and management of Crohn's disease of the ileal pouch have been challenging. A
      combined assessment of clinical history, endoscopy, histology, abdominal/pelvic
      imaging, and examination under anesthesia is often necessary for accurate
      diagnosis, disease classification, management, and prognosis. A multidisciplinary
      approach with gastroenterologists, colorectal surgeons, gastrointestinal
      pathologists, and radiologists is advocated.

PMID- 22855238
TI  - Treatment response evaluation by MRI in breast cancer patients receiving
      neoadjuvant chemotherapy: there is more than just pathologic complete response
      prediction.

PMID- 22855237
TI  - Identification of Cys94 as the distal ligand to the Fe(III) heme in the
      transcriptional regulator RcoM-2 from Burkholderia xenovorans.
AB  - The CO-responsive transcriptional regulator RcoM from Burkholderia xenovorans
      (BxRcoM) was recently identified as a Cys(thiolate)-ligated heme protein that
      undergoes a redox-mediated ligand switch; however, the Cys bound to the Fe(III)
      heme was not identified. To that end, we generated and purified three Cys-to-Ser
      variants of BxRcoM-2--C94S, C127S, and C130S--and examined their spectroscopic
      properties in order to identify the native Cys(thiolate) ligand. Electronic
      absorption, resonance Raman, and electron paramagnetic resonance (EPR)
      spectroscopies demonstrate that the C127S and C130S variants, like wild-type
      BxRcoM-2, bind a six-coordinate low-spin Fe(III) heme using a Cys/His ligation
      motif. In contrast, electronic absorption and resonance Raman spectra of the C94S
      variant are most consistent with a mixture of five-coordinate high-spin and six
      coordinate low-spin Fe(III) heme, neither of which are ligated by a Cys(thiolate)
      ligand. The EPR spectrum of C94S is dominated by a large, axial high-spin Fe(III)
      signal, confirming that the native ligation motif is not maintained in this
      variant. Together, these data reveal that Cys(94) is the distal Fe(III) heme
      ligand in BxRcoM-2; by sequence alignment, Cys(94) is also implicated as the
      distal Fe(III) heme ligand in BxRcoM-1, another homologue found in the same
      organism.

PMID- 22855239
TI  - Breast fat and breast cancer.

PMID- 22855240
TI  - Novel percutaneous radiofrequency ablation of portal vein tumor thrombus: safety
      and feasibility.
AB  - PURPOSE: We report our experience of the safety of partial recanalization of the
      portal vein using a novel endovascular radiofrequency (RF) catheter for portal
      vein tumor thrombosis. METHODS: Six patients with liver cancer and tumor thrombus
      in the portal vein underwent percutaneous intravascular radiofrequency ablation
      (RFA) using an endovascular bipolar RF device. A 0.035-inch guidewire was
      introduced into a tributary of the portal vein and through which a 5G guide
      catheter was introduced into the main portal vein. After manipulation of the
      guide catheter over the thrombus under digital subtraction angiography, the
      endovascular RF device was inserted and activated around the thrombus. RESULTS:
      There were no observed technique specific complications, such as hemorrhage,
      vessel perforation, or infection. Post-RFA portography showed partial
      recanalization of portal vein. CONCLUSIONS: RFA of portal vein tumor thrombus in
      patients with hepatocellular carcinoma is technically feasible and warrants
      further investigation to assess efficacy compared with current recanalization
      techniques.

PMID- 22855241
TI  - Larvicidal and pupicidal activity of extracts and fractionates of Eichhornia
      crassipes (Mart.) Solms against the filarial vector Culex quinquefasciatus Say.
AB  - Petroleum ether, acetone, ethyl acetate, aqueous extract, methanol and ethanol
      fractionate of Eichhornia crassipes (Mart.) Solms was tested for their larvicidal
      efficacy against the different instars (I, II, III and IV) and pupae of Culex
      quinquefasciatus Say. The larval mortality was observed after 24 h of the
      treatment. The extracts showed a dose-dependent toxicity to larvae. The toxicity
      of the extracts decreased with increase in larval stage. Ethanol fractionate of
      E. crassipes showed the highest larvicidal and pupicidal activity against C.
      quinquefasciatus compared to other solvent extracts and fractionates with LC(50)
      71.43, 94.68,120.42, 152.15 and 173.35 ppm for I, II, III, IV and pupae,
      respectively. Presence of metabolites like flavonoids, alkaloids, anthroquinones
      and anthocyanins in the tested extracts might be the reason for the larvicidal
      and pupicidal activity of the plant extracts and fractionates of waterhyacinth.
      Mosquito-repellent activity was not exhibited by these extracts at the tested
      concentrations. The results demonstrated the potential of the aquatic plant E.
      crassipes in the successful control of the filarial vector C. quinquefasciatus.

PMID- 22855242
TI  - Molecular characterization of avian malaria parasites in three Mediterranean blue
      tit (Cyanistes caeruleus) populations.
AB  - We genetically analysed malaria parasites (Protozoa) in three Mediterranean blue
      tit (Cyanistes caeruleus) populations from central Spain. A total of 853 breeding
      individuals were screened for parasites of the genera Plasmodium and Haemoproteus
      using a very efficient polymerase chain reaction approach that amplifies a
      partial segment of the mitochondrial cytochrome b gene of these parasites. We
      have found six lineages of Plasmodium (SGS1, GRW11, COLL1, DELURB4, GRW04 and
      BLUTI10) parasitizing the studied populations but we did not detect any infection
      by Haemoproteus. One of the detected lineages (BLUTI10) has not been previously
      described in any bird species and this is the first study recording lineages
      DELURB4 and GRW04 in blue tits. SGS1 (belonging to the morphospecies Plasmodium
      relictum) was the most frequent lineage (overall prevalence, 24 %), whereas the
      other lineages showed a much lower prevalence (<4 %). Only a small proportion
      (12.2 %) of positive amplifications of the most common lineage (SGS1) was
      detected in blood smears using light microscopy and infection intensities were
      very low (mean +/- SE, 2.0 +/- 1.4 parasites/2,000 erythrocytes). We have also
      found strong inter-population variability in prevalence patterns (12-41 % for
      lineage SGS1), suggesting important differences in parasite transmission rates
      among the geographically close studied localities.

PMID- 22855243
TI  - pH effects on binding between the anthrax protective antigen and the host
      cellular receptor CMG2.
AB  - The anthrax protective antigen (PA) binds to the host cellular receptor capillary
      morphogenesis protein 2 (CMG2) with high affinity. To gain a better understanding
      of how pH may affect binding to the receptor, we have investigated the kinetics
      of binding as a function of pH to the full-length monomeric PA and to two
      variants: a 2-fluorohistidine-labeled PA (2-FHisPA), which is ~1 pH unit more
      stable to variations in pH than WT, and an ~1 pH unit less stable variant in
      which Trp346 in the domain 2beta(3) -2beta(4)  loop is substituted with a Phe
      (W346F). We show using stopped-flow fluorescence that the binding rate increases
      as the pH is lowered for all proteins, with little influence on the rate of
      dissociation. In addition, we have crystallized PA and the two variants and
      examine the influence of pH on structure. In contrast to previous X-ray studies,
      the domain 2beta(3) -2beta(4)  loop undergoes little change in structure from pH
      ~8 to 5.5 for the WT protein, but for the 2-FHis labeled and W346F mutant there
      are changes in structure consistent with previous X-ray studies. In accord with
      pH stability studies, we find that the average B-factor values increase by ~20
      30% for all three proteins at low pH. Our results suggest that for the full
      length PA, low pH increases the binding affinity, likely through a change in
      structure that favors a more "bound-like" conformation.

PMID- 22855244
TI  - [Progressive cranial nerve deficits after frontotemporal squamous cell carcinoma
      of the skin].

PMID- 22855245
TI  - [One tumor of the parotid gland, 2 aetiological findings].

PMID- 22855246
TI  - Organocatalytic asymmetric direct C(sp3)-H functionalization of ethers: a highly
      efficient approach to chiral spiroethers.

PMID- 22855250
TI  - Cutaneous disseminated sporotrichosis complicated by osteomyelitis.

PMID- 22855251
TI  - Need for mental health services and service use among high school students in
      China.
AB  - OBJECTIVE: Rapid economic growth and social change in China in recent years have
      been accompanied by increased rates of mental health problems among the country's
      adolescents. This study examined rates of mental health service use and
      associated factors among Chinese adolescents. METHODS: A survey of 1,891 high
      school students in grades ten through 12 from three high schools in Shantou,
      China, was conducted in 2009. Measures of mental health status, service need
      (perceived and objective), mental health service use, and informal help seeking
      were obtained. RESULTS: Twenty-five percent of the adolescents reported a
      perceived need for the services of a mental health professional. Only 5% of the
      sample had used school-based mental health services and only 4% had used non
      school-based services. Three factors emerged as independently associated with
      adolescent use of both school-based and non-school-based services: perceiving a
      need for mental health services, having turned to a teacher for help, and having
      turned to a relative other than one's parents for help. Male gender, being a 12th
      grader, and being an only child were independently associated with use of school
      based services only, whereas a suicide attempt and having turned to one's parents
      for help were independently associated with use of non-school-based services.
      CONCLUSIONS: Findings indicate a high level of unmet need for mental health
      services among Chinese adolescents and highlight the need to improve the mental
      health knowledge of parents, teachers, and other significant individuals in
      adolescents' lives to facilitate adolescents' access to the mental health
      services that they need.

PMID- 22855252
TI  - Transport, metabolism, cytotoxicity and effects of novel taxanes on the cell
      cycle in MDA-MB-435 and NCI/ADR-RES cells.
AB  - Resistance of tumours to taxanes causes chemotherapy failure in numerous
      patients. Resistance is partly due to the low tumour uptake of taxanes and their
      rapid metabolism. Structural modifications of taxanes can reduce their P
      glycoprotein-related efflux or decrease metabolism and consequently increase
      taxane efficiency. This study compared cytotoxicity and effects of the cell
      cycle, transport and metabolism of novel taxanes SB-T-1102, SB-T-1103, SB-T-1214
      and SB-T-1216, fluorinated SB-T-12851, SB-T-12852, SB-T-12853, SB-T-12854 and
      IDN5109 with paclitaxel in paclitaxel-sensitive (MDA-MB-435) and paclitaxel
      resistant (NCI/ADR-RES) human cancer cells. We have shown before that NCI/ADR-RES
      cells were 1,000-fold less sensitive to paclitaxel than MDA-MB-435 cells in
      correspondence to P-glycoprotein overexpression and up to 20-fold lower uptake of
      the drug in the resistant cells. The uptake of novel taxanes was 1.2 to 3.8 times
      lower than that of paclitaxel in the MDA-MB-435 cells, but 1.5 to 6.5 times
      higher in NCI/ADR-RES cells. NCI/ADR-RES cells were correspondingly only 2- to
      6.6-fold less sensitive than the MDA-MB-435 cells to novel taxanes. Both cell
      lines showed minimal metabolism of the novel taxanes which was therefore not
      responsible for their different sensitivity, the observed differences in their
      individual efficiency and higher effects than paclitaxel. All novel taxanes
      caused G(2)/M block of the cell cycle similar to paclitaxel, but lower at
      concentrations by order of magnitude. Thus, structural modifications of taxanes
      resulting in their decreased P-glycoprotein-related transport probably caused
      their higher efficiency than paclitaxel in multidrug-resistant NCI/ADR-RES tumour
      cells.

PMID- 22855253
TI  - Accuracy of self-reported sun exposure and sun protection behavior.
AB  - The objective of this study was to compare the accuracy of self-reported skin
      cancer risk outcome measures proposed as standards by prevention experts to
      aggregated estimates of behavior from weekly diaries. Weekly electronic diaries
      of ultraviolet radiation (UVR) behaviors, initially validated by comparison with
      daily electronic diaries, were used to assess the accuracy of commonly used end
      of-summer self-reported measures among 250 adults. Results revealed low biases,
      and good correspondence between simple open-ended self-reported estimates of days
      outside, hours outside, sunbathing days and hours, and days outside when not
      protected by either sunscreen, long-sleeved shirts, hats, or shade. Rating scale
      measures commonly used in the current literature and those recently recommended
      as standards by a workshop of experts showed evidence of being non-interval and
      lacking precision for more frequent behavior (e.g., >1 h sun exposure daily).
      These data indicated that open-ended frequency self-reports of skin cancer risk
      behaviors that follow procedures designed to increase accuracy were reliable over
      a summer-long period.

PMID- 22855255
TI  - An incidence estimation model for multi-stage diseases with differential
      mortality.
AB  - Prevalence and incidence are two important measures of the impact of a disease.
      For many diseases, incidence is the most useful measure for response planning.
      However, the longitudinal studies needed to calculate incidence are resource
      intensive, so prevalence estimates are often more readily available. In 1986,
      Podgor and Leske (Statistics in Medicine, 5:573-578, 1986) developed a model to
      estimate incidence of a single disease from one survey of age-specific
      prevalence, even where the presence of the disease increases the mortality rate
      of patients. Here, we extend their model to the case of progressive diseases,
      where the incidence of all disease stages is desired. As an example, we consider
      the case of cataract disease in Africa, where ophthalmologists wish to
      distinguish between unilateral and bilateral cataract incidence in order to plan
      the number of cataract surgeries needed to prevent the occurrence of blindness as
      a result of the disease. Our method has successfully provided cataract incidence
      estimates on the basis of prevalence data from new Rapid Assessment of Avoidable
      Blindness surveys in Africa (Lewallen et al., Archives of Ophthalmology,
      128(12):1584-1589, 2010). In this paper, we provide a more general form of the
      model in order to promote its applicability to other diseases.

PMID- 22855254
TI  - Derivation of vascular endothelial cells from human embryonic stem cells under
      GMP-compliant conditions: towards clinical studies in ischaemic disease.
AB  - Revascularisation of ischaemic tissue remains an area of substantial unmet
      clinical need in cardiovascular disease. Strategies to induce therapeutic
      angiogenesis are therefore attractive. Our recent focus has been on human
      embryonic stem cell (hESC) strategies since hESC can be maintained in a
      pluripotent state or differentiated into any desired cell type, including
      endothelial cells (EC), under defined differentiation culture conditions. We
      recently published a protocol for non-good manufacturing practice (GMP) feeder-
      and serum-free hESC-EC-directed monolayer differentiation to vascular EC
      demonstrating the potential to generate hESC-derived EC in a GMP-compliant manner
      suitable for use in clinical trials. In this study we modified that laboratory
      protocol to GMP compliance. EC production was confirmed by flow cytometry, qRT
      PCR and production of vascular structures in Matrigel(r), yielding approximately
      30 % mature VE-cadherin(+)/PECAM-1(+) cells using the GMP-compliant hESC line
      RC13. In conclusion, we have successfully demonstrated the production of vascular
      EC under GMP-compliant conditions suitable for clinical evaluation.

PMID- 22855256
TI  - Thyrolinguofacial trunk arising from the carotid bifurcation determined by three
      dimensional computed tomography angiography.
AB  - It is recognized that the branches of the external carotid artery (ECA) can show
      variation, but the presence of a thyrolinguofacial trunk is extremely rare and
      always originates from the ECA. We report a case of the thyrolinguofacial trunk
      arising from the carotid bifurcation (CB) on the left side in a 76-year-old man
      with advanced tongue cancer, as revealed by three-dimensional computed tomography
      angiography for vascular mapping of the carotid vessels prior to superselective
      intra-arterial catheterization. The thyrolinguofacial trunk arose 1.6 mm below
      the CB from the anterior surface of the left CB. The inner diameter of the
      thyrolinguofacial trunk at origin was 4.4 mm and the angle between the
      thyrolinguofacial trunk and CB was 128 degrees . After a 1.7-mm course, the trunk
      divided into the superior thyroid artery and a linguofacial trunk, the inner
      diameters of which were 1.5 and 3.4 mm, respectively, at origin. The angle
      between the two arteries was 88 degrees . After a 9.8-mm course from the
      bifurcation, the linguofacial trunk divided into the lingual artery and facial
      artery, the inner diameters of which were 1.8 and 1.9 mm, respectively, at
      origin. The angle between the two arteries was 61 degrees . It is important to
      recognize such an anatomic variation of the branches of the ECA prior to
      superselective intra-arterial catheterization or microsurgical reconstruction for
      head and neck cancer.

PMID- 22855257
TI  - Risk factors for colon cancer in 150,912 postmenopausal women.
AB  - BACKGROUND: Prospective data from the Women's Health Initiative were analyzed to
      evaluate more than 800 possible risk factors for an association with colon cancer
      in postmenopausal women. METHODS: Data included 150,912 postmenopausal women
      between the ages of 50 and 79. The Cox proportional hazard regression analysis
      was used to identify risk factors independently associated with the development
      of colon cancer during a median follow-up time of 8 years. RESULTS: A total of
      1,210 women developed colon cancer and 282 developed rectal cancer. Eleven risk
      factors were independently associated with an increased risk of colon cancer at
      the p < 0.001 level. In decreasing order of associated chi(2) values, they were
      age, waist girth (especially for subjects without diabetes), use of hormone
      therapy at baseline (protective), years smoked, arthritis (protective presumably
      because of medications used for treatment), relatives with colorectal cancer,
      lower hematocrit levels, fatigue, diabetes, less use of sleep medication, and
      cholecystectomy. Of the 11 factors, three were significantly associated with an
      increased risk of rectal cancer: age, waist, and not taking hormone therapy.
      CONCLUSIONS: The results provide additional support for the importance of waist
      girth, hormone therapy, smoking, NSAID use, diabetes, and cholecystectomy as risk
      factors for colon cancer. Some factors previously identified as influencing risk
      (exercise and black race) did not have a strong independent association with
      colon cancer in this analysis.

PMID- 22855258
TI  - Bootstrap-based inference on the difference in the means of two correlated
      functional processes.
AB  - We propose nonparametric inference methods on the mean difference between two
      correlated functional processes. We compare methods that (1) incorporate
      different levels of smoothing of the mean and covariance; (2) preserve the
      sampling design; and (3) use parametric and nonparametric estimation of the mean
      functions. We apply our method to estimating the mean difference between average
      normalized delta power of sleep electroencephalograms for 51 subjects with severe
      sleep apnea and 51 matched controls in the first 4  h after sleep onset. We
      obtain data from the Sleep Heart Health Study, the largest community cohort study
      of sleep. Although methods are applied to a single case study, they can be
      applied to a large number of studies that have correlated functional data.

PMID- 22855259
TI  - Inflammed skin harbours Th9 cells.

PMID- 22855260
TI  - Interaction between isolated transcriptional activation domains of Sp1 revealed
      by heteronuclear magnetic resonance.
AB  - The promoter-specific transcription factor Sp1 is expressed ubiquitously, and
      plays a primary role in the regulation of the expression of many genes. Domains A
      and B located in the N-terminal half of the protein are characterized by
      glutamine-rich (Q-rich) sequences. These Q-rich domains have been shown to be
      involved in the interaction between Sp1 and different classes of nuclear
      proteins, such as TATA-binding protein associated factors. Furthermore, the self
      association of Sp1 via Q-rich domains is also important for the regulation of
      transcriptional activity. It has been considered that an Sp1 molecule bound to a
      "distal" GC-box synergistically interacts with another Sp1 molecule at a
      "proximal" binding site. Although the formation of multimers via Q-rich domains
      seems functionally important for Sp1, little is known about the structural and
      physicochemical nature of the interaction between Q-rich domains. We analyzed the
      structural details of isolated glutamine-rich B (QB) domains of Sp1 by circular
      dichroism (CD), analytical ultracentrifugation, and heteronuclear magnetic
      resonance spectroscopy (NMR). We found the isolated QB domains to be disordered
      under all conditions examined. Nevertheless, a detailed analysis of NMR spectra
      clearly indicated interaction between the domains. In particular, the C-terminal
      half was responsible for the self-association. Furthermore, analytical
      ultracentrifugation demonstrated weak but significant interaction between
      isolated QB domains. The self-association between QB domains would be
      responsible, at least in part, for the formation of multimers by full-length Sp1
      molecules that has been proposed to occur during transcriptional activation.

PMID- 22855261
TI  - Changing trends in inpatient care for psychiatrically hospitalized youth: 1991
      2008.
AB  - Research has focused on changes in the psychiatric treatment of youth in
      outpatient settings, but less is known about trends in inpatient care. This study
      documents changes in the lengths of stay (LOS), clinical profiles of youth, and
      medication use within an inpatient setting in Massachusetts between 1991 and
      2008. A chart review of 233 medical records of psychiatrically hospitalized youth
      was conducted at three points in time (1991, 1998, and 2008). Sample includes
      youth between ages 4 and 18. Clinical data, including LOS, diagnoses and other
      clinical variables, and number and type of medications prescribed were compared
      across sample years. Findings indicate a significant decrease in the LOS coupled
      with a concurrent increase in psychotropic medication use between each successive
      sample year. The prescription of anti-psychotic medications, in particular,
      increased significantly. On clinical indices, findings show that there was an
      increase in the diagnosis of bipolar spectrum disorders and a concurrent decrease
      in unipolar diagnoses in the 2008 sample. Attention-deficit and developmental
      disorders showed little change. Trauma-related disorders were significantly less
      frequently diagnosed in 2008. Children hospitalized in 1998 and 2008 had more
      prior hospitalizations and presented with greater acuity than those in the 1991
      sample. Results highlight important changes that have occurred in
      child/adolescent inpatient settings over the past two decades. Data suggest that
      these changes have not resulted in decreased rates of inpatient hospitalization
      for youth with more severe psychiatric disorders.

PMID- 22855262
TI  - The flavonoids hesperidin and rutin promote neural crest cell survival.
AB  - The neural crest (NC) corresponds to a collection of multipotent and oligopotent
      progenitors endowed with both neural and mesenchymal potentials. The derivatives
      of the NC at trunk level include neurons and glial cells of the peripheral
      nervous system in addition to melanocytes, smooth muscle cells and some endocrine
      cells. Environmental factors control the fate decisions of NC cells. Despite the
      well-known influence of flavonoids on the central nervous system, the issue of
      whether they also influence NC cells has not been yet addressed. Flavonoids are
      polyphenolic compounds that are integral components of the human diet. The
      biological activities of these compounds cover a very broad spectrum, from
      anticancer and antibacterial activities to inhibition of bone reabsorption and
      modulation of inflammatory response. In the present work, we have investigated
      the actions of the flavonoids hesperidin, rutin and quercetin on NC cells of
      quail, in vitro. We show for the first time, that hesperidin and rutin increase
      the viability of trunk NC cells in culture, without affecting cell
      differentiation and proliferation. The molecular mechanism of this action is
      dependent on ERK2 and PI3K pathways. Quercetin had no effect on NC progenitors.
      Taken together, these results suggest that flavonoids hesperidin and rutin
      increase NC cell survival, which may be useful against the toxicity of some
      chemicals during embryonic development.

PMID- 22855263
TI  - Copper-catalyzed cross-coupling of functionalized alkyl halides and tosylates
      with secondary and tertiary alkyl Grignard reagents.
AB  - Added value: A copper-based method is highly efficient for the cross-coupling of
      alkyl electrophiles with secondary and tertiary alkyl Grignard reagents. The
      method is distinguished by its broad substrate scope and high functional group
      tolerance.

PMID- 22855264
TI  - Social support and religion: mental health service use and treatment of
      schizophrenia.
AB  - The perceptions and religious beliefs held by family members, mental health and
      health care professionals, and the community may affect the treatment of
      individuals with schizophrenia. To better identify and understand the influence
      of families, professionals and community members on individual's treatment for
      schizophrenia, this review paper examines: (1) the religious perceptions of
      families, professionals, and the public towards schizophrenia; (2) religious
      perceptions of the etiology of schizophrenia; (3) how others perceive religion as
      a coping mechanism; and (4) how religion influences treatment engagement and help
      seeking behaviors. MEDLINE and PsycInfo databases were systematically searched
      from 1980 to 2010 using the terms schizophrenia, schizoaffective,
      schizophreniform, psychotic disorder not otherwise specified and religion,
      religiosity, spirituality, and faith. Forty-three (n = 43) original research
      studies met the inclusion criteria. This study found that religious beliefs
      influence the treatment of schizophrenia in the following ways: Religious themes
      were positively associated with coping, treatment engagement and help-seeking
      behavior. Evidence of religious underpinnings was found in perceptions of
      etiology. The findings also indicate that there is often both a preference among
      family members and caregivers to utilize religious-based professionals and
      caution toward mental health professionals. Researchers and professionals may
      find avenues for improving treatment through examining the interaction of
      religious and schizophrenia at the social support level. 

PMID- 22855265
TI  - In vitro investigation of fluorescence of carious dentin observed with a
      Soprolife(r) camera.
AB  - OBJECTIVES: Our aim was to determine the origin of the red fluorescence of
      carious dentine observed with the Soprolife(r) camera. METHODS: We conducted in
      vitro studies to evaluate the origin of the red fluorescence using acids and
      matrix metalloproteinase (MMP) to mimic caries and methylglycoxal (MGO) to
      evaluate the effect of glycation reactions on the red fluorescence. In every step
      of these models, we detected the changes of dentin photonic response with
      Soprolife(r) in daylight mode and in treatment mode. A Raman spectroscopy
      analysis was performed to determine the variations of the dentin organic during
      the in vitro caries processes. Raman microscopy was performed to identify change
      in the collagen matrix of dentine. RESULTS: The red fluorescence observed in
      carious dentine using a Soprolife(r) camera corresponds to the brownish color
      observed using daylight. Demineralization using nitric acid induces a loss of the
      green fluorescence of dentine. The red fluorescence of carious dentine is
      resistant to acid treatment. Immersion of demineralized dentine in MGO induces a
      change of color from white to orange-red. This indicates that the Maillard
      reaction contributes to lesion coloration. Immersion of demineralized dentine in
      an MMP-1 solution followed by MGO treatment results in a similar red
      fluorescence. Raman microspectroscopy analysis reveals accumulation of AGE's
      product in red-colored dentine. CONCLUSIONS: Our results provide important
      information on the origin of the fluorescence variation of dentine observed with
      the Soprolife(r) camera. We demonstrate that the red fluorescence of carious
      dentine is linked to the accumulation of Advanced Glycation End products (AGE).
      CLINICAL RELEVANCE: The study provides a new biological basis for the red
      fluorescence of carious dentine and reinforces the importance of the Soprolife(r)
      camera in caries diagnostics.

PMID- 22855266
TI  - Biofilm formation on stainless steel and gold wires for bonded retainers in vitro
      and in vivo and their susceptibility to oral antimicrobials.
AB  - OBJECTIVE: Bonded retainers are used in orthodontics to maintain treatment
      result. Retention wires are prone to biofilm formation and cause gingival
      recession, bleeding on probing and increased pocket depths near bonded retainers.
      In this study, we compare in vitro and in vivo biofilm formation on different
      wires used for bonded retainers and the susceptibility of in vitro biofilms to
      oral antimicrobials. MATERIALS AND METHODS: Orthodontic wires were exposed to
      saliva, and in vitro biofilm formation was evaluated using plate counting and
      live/dead staining, together with effects of exposure to toothpaste slurry alone
      or followed by antimicrobial mouthrinse application. Wires were also placed intra
      orally for 72 h in human volunteers and undisturbed biofilm formation was
      compared by plate counting and live/dead staining, as well as by denaturing
      gradient gel electrophoresis for compositional differences in biofilms. RESULTS:
      Single-strand wires attracted only slightly less biofilm in vitro than multi
      strand wires. Biofilms on stainless steel single-strand wires however, were much
      more susceptible to antimicrobials from toothpaste slurries and mouthrinses than
      on single-strand gold wires and biofilms on multi-strand wires. Also, in vivo
      significantly less biofilm was found on single-strand than on multi-strand wires.
      Microbial composition of biofilms was more dependent on the volunteer involved
      than on wire type. CONCLUSIONS: Biofilms on single-strand stainless steel wires
      attract less biofilm in vitro and are more susceptible to antimicrobials than on
      multi-strand wires. Also in vivo, single-strand wires attract less biofilm than
      multi-strand ones. CLINICAL SIGNIFICANCE: Use of single-strand wires is preferred
      over multi-strand wires, not because they attract less biofilm, but because
      biofilms on single-strand wires are not protected against antimicrobials as in
      crevices and niches as on multi-strand wires.

PMID- 22855267
TI  - In vivo hemostatic efficacy of polyurethane foam compared to collagen and
      gelatin.
AB  - OBJECTIVES: Topical hemostatic agents are used in all surgical disciplines. Most
      of these hemostats are based on animal-derived products like collagen and
      gelatin. They carry the potential risk of pathogen transmission. A newly
      developed biodegradable, fully synthetic hemostatic agent based on polyurethane
      foam (PU) with 55 % polyethylene glycol (PEG) would prevent these potential
      risks. MATERIALS AND METHODS: The hemostatic efficacy of this new agent was
      compared to gelatin and collagen in humans who underwent extraction of an upper
      and lower molar (split-mouth model). After extraction of a molar in the maxilla
      and mandible, a PU foam and collagen or gelatin were inserted in the extraction
      socket for 2 min. Hereafter, the agents were removed and stored in
      ethylenediaminetetraacetic acid to stop coagulation. Then, the concentration of
      coagulation parameters thrombin-antithrombin III (TAT) complexes, fibrinogen, and
      thromboxane B2 (TxB2) in blood extracts from the agents was measured. The
      concentrations were also determined in baseline blood samples which were
      collected from the extraction socket. RESULTS: The concentrations of TAT and TxB2
      were significantly increased, and fibrinogen concentration was significantly
      reduced compared to baseline wound blood concentrations indicating enhanced
      hemostasis. No significant differences were seen in the concentrations of these
      coagulation parameters in the three different hemostatic agents. CONCLUSIONS:
      These results show that PU combined with 55 % PEG is a promising alternative for
      the animal-derived hemostatic agents. CLINICAL RELEVANCE: The synthetic
      hemostatic agent could replace the animal-derived products like collagen and
      gelatin and therewith prevent the potential risk of pathogen transmission.

PMID- 22855268
TI  - Serious mental illness and risk of new HIV/AIDS diagnoses: an analysis of
      Medicaid beneficiaries in eight states.
AB  - OBJECTIVE: A longitudinal analysis was used to explore the relationship between
      diagnosis of serious mental illness and subsequent new diagnoses of HIV. METHODS:
      Logistic regression was used to predict HIV/AIDS diagnoses in 2002-2004 among
      Medicaid beneficiaries in eight states (N=6,417,676) who were without HIV in
      2001. Results for beneficiaries with and without serious mental illness, a
      substance use disorder, and psychiatric comorbidities in 2001 were compared.
      RESULTS: After controlling for substance abuse or dependence and other factors,
      the analyses indicated that the odds of new HIV/AIDS diagnoses among
      beneficiaries with or without serious mental illness did not differ
      significantly. Compared with beneficiaries without a substance use disorder or
      serious mental illness, individuals with a substance use disorder but without
      serious mental illness were 3.1 times (OR=3.13, p<.001) more likely, and those
      with both substance abuse or dependence and serious mental illness were 2.1 times
      (OR=2.09, p<.001) more likely, to receive a new HIV diagnosis in 2002-2004.
      However, people with serious mental illness but without a substance use disorder
      in 2001 were 23% less likely (OR=.77, p<.001) than people without serious mental
      illness or a substance use disorder in 2001 to receive a new HIV diagnosis.
      CONCLUSIONS: After substance abuse or dependence was controlled for
      longitudinally, little independent association between serious mental illness and
      the risk of new HIV diagnoses was found. HIV-prevention services for low-income
      individuals should be delivered to all persons with serious mental illness, but
      especially those with comorbid substance use disorders.

PMID- 22855269
TI  - Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug
      interactions.
AB  - The use of herbal/botanical products, also referred to as complementary and
      alternative medicines (CAM), worldwide enjoys increasing popularity. It appears
      in particular highly prevalent in patient populations already exposed to complex
      treatment algorithms and polypharmacotherapy, frequently involving narrow
      therapeutic index drugs. Accordingly, the potential clinical dimension and
      relevance of herb-drug interactions has received considerable attention over the
      last years. However, review of pertinent literature indicates that the available
      clinical evidence in this regard is still limited and sometimes inconclusive.
      Also, communication of herb-drug interaction data in the
      biopharmaceutical/medical literature is often complex and confusing, not always
      unbiased, and in many cases appears not to strive for clear-cut and useful
      guidance in terms of the clinical relevance of such findings.This systematic
      review summarizes and interprets the published evidence on clinical herb-drug
      interaction studies which examined the potential of six popular herbal drugs
      (Echinacea, garlic, gingko, ginseng, goldenseal, and milk thistle) as
      perpetrators of pharmacokinetic (PK) drug interactions. Reported effect sizes
      were systematically categorized according to FDA drug interaction guideline
      criteria. A total of 66 clinical PK interaction studies, meeting the scope of the
      present review, were identified. The clinical evidence was found to be most
      robust and informative for Gingko biloba (GB; 21 studies) and milk
      thistle/silymarin (MT; 13), and appears still limited for ginseng (9),
      goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the
      available evidence indicates that, at commonly recommended doses, none of these
      herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP)
      enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or
      inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition,
      CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition),
      GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic
      CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses).
      Information was found not always complete for the major drug metabolizing CYP
      enzymes in the less well-studied herbs and is largely limited to P-glycoprotein
      (ABCB1) when effects on drug transporters have been investigated.

PMID- 22855270
TI  - Small-molecule STAT3 signaling pathway modulators from Polygonum cuspidatum.
AB  - Constitutively activated STAT3 plays a pivotal role in oncogenesis and metastasis
      in many human cancers, and STAT3 has been validated as a novel anticancer drug
      target. Thus, the identification of small molecules that modulate STAT3 activity
      could be of great therapeutic importance. The aim of this study was to isolate
      novel modulators of the STAT3 signaling pathway from the roots of Polygonum
      cuspidatum by bioassay-guided fractionation using a STAT3 reporter gene assay. 2
      Methoxystypandrone (1), as well as three anthraquinones (2-4), were identified as
      major active components of P. cuspidatum. Compound 1 demonstrated a potent
      inhibitory effect on STAT3 activation and significantly inhibited cell
      proliferation of human breast cancer cells, especially those with constitutively
      activated STAT3 (IC50 = 2.7-3.1 uM). The SAR analysis of quinone analogues
      suggested that the phenolic and carbonyl groups are the key structures
      contributing to their inhibitory activities against the STAT3 signaling.

PMID- 22855272
TI  - Rapidly involuting congenital melanocytic naevi in two children.

PMID- 22855271
TI  - The PDE5 inhibitor vardenafil does not affect auditory sensory gating in rats and
      humans.
AB  - RATIONALE: Sensory gating is an adaptive mechanism of the brain to prevent
      overstimulation. Patients suffering from clinical disorders such as Alzheimer's
      disease or schizophrenia exhibit a deficit in gating, which indicates not only an
      impairment in basic information processing that might contribute to the cognitive
      problems seen in these patients. Phosphodiesterase type 5 inhibitors (PDE5-Is)
      have been shown to improve cognition in rodents in various behavioural tasks and
      might consequently be an interesting target for cognition enhancement. However,
      the effects of PDE5-Is on sensory gating are not known yet. OBJECTIVES: This work
      aims to study the effects of PDE5 inhibition on auditory sensory gating in rats
      and humans. METHODS: In the rat study, vehicle or 0.3-3 mg/kg of the PDE5-I
      vardenafil was given orally 30 min before testing and electrode locations were
      the vertex, hippocampus and the striatum. The human subjects received placebo, 10
      20 mg vardenafil 85 min before testing and sensory gating was measured at the
      cortex (Fz, Fcz and Cz) electrodes. RESULTS: Significant gating was only found
      for the N1 component in rats while all three peaks P1, N1 and P2 showed gating in
      humans, i.e. the response to the second sound click was decreased as compared
      with the first for these deflections. Administration of vardenafil did neither
      have an effect on sensory gating in rats nor in humans. CONCLUSIONS: These
      findings imply that positive effects of PDE5 inhibition on cognition are not
      mediated by more early phases of information processing.

PMID- 22855273
TI  - L-Asparaginase, nitric oxide and posterior reversible encephalopathy syndrome.

PMID- 22855275
TI  - Utilization and costs of conventional and alternative pharmaceuticals in
      children: results from the German GINIplus and LISAplus birth cohort studies.
AB  - PURPOSE: The socioeconomic determinants for drug utilization, especially in
      children, have not been investigated sufficiently so far. The study's aim was the
      estimation of prevalences and determinants of conventional, homeopathic and
      phytotherapeutic drugs and expenditures. METHODS: Population-based data on drug
      utilization of 3,642 children in two German birth cohorts (GINIplus and LISAplus,
      10-year follow-up) were collected using a self-administered questionnaire. For
      analysis, the reported drugs (use within the last four weeks) were classified
      into the therapeutic categories of 'conventional medicine', 'homeopathy',
      'phytotherapy' and 'others'. Drug costs were estimated using pharmaceutical
      identification numbers. RESULTS: In all, 42.3% of the children reported drug use;
      24.1% of the drugs were homeopathic and 11.5% were phytotherapeutic. The
      proportion of children who took at least one homeopathic remedy was 14.3%. Drugs
      prescribed by physicians were dominated by conventional medicine (76.5%), whereas
      in non-prescribed drugs, both homeopathy and conventional medicine accounted for
      37% each. Boys (OR = 0.78) used less homeopathy than girls. Income showed only a
      weak influence. Education had a strong effect on the use of phytotherapy such
      that children of mothers with higher school education (>10 years vs. <10 years)
      used more phytotherapy (OR = 2.01). If out-of-pocket payments arose (n = 613),
      the mean was ?20. On average, total drug expenditures summed up to ?39 in 4 weeks
      for drug users if only clearly identifiable prices for drugs were considered (58%
      of all data). CONCLUSIONS: Utilization of homeopathy is common in children from
      the analyzed cohort. User profiles of homeopathy and phytotherapy differ from
      each other and should be analyzed separately.

PMID- 22855277
TI  - Body fat loss and compensatory mechanisms in response to different doses of
      aerobic exercise--a randomized controlled trial in overweight sedentary males.
AB  - The amount of weight loss induced by exercise is often disappointing. A diet
      induced negative energy balance triggers compensatory mechanisms, e.g., lower
      metabolic rate and increased appetite. However, knowledge about potential
      compensatory mechanisms triggered by increased aerobic exercise is limited. A
      randomized controlled trial was performed in healthy, sedentary, moderately
      overweight young men to examine the effects of increasing doses of aerobic
      exercise on body composition, accumulated energy balance, and the degree of
      compensation. Eighteen participants were randomized to a continuous sedentary
      control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high
      exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ~30 and 60 min of
      daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH:
      -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P <
      0.001) decreased similarly in both exercise groups. Although the exercise-induced
      energy expenditure in HIGH was twice that of MOD, the resulting accumulated
      energy balance, calculated from changes in body composition, was not different
      (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more
      negative than expected in MOD, while it was 20% less negative than expected in
      HIGH. No statistically significant changes were found in energy intake or
      nonexercise physical activity that could explain the different compensatory
      responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion,
      a similar body fat loss was obtained regardless of exercise dose. A moderate dose
      of exercise induced a markedly greater than expected negative energy balance,
      while a higher dose induced a small but quantifiable degree of compensation.

PMID- 22855276
TI  - Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial
      function in humans with uncomplicated type 1 diabetes mellitus.
AB  - Studies of experimental diabetes mellitus (DM) suggest that increased nitric
      oxide (NO) bioactivity contributes to renal hyperfiltration. However, the role of
      NO in mediating hyperfiltration has not been fully elucidated in humans. Our aim
      was to examine the effect of NO synthase inhibition on renal and peripheral
      vascular function in normotensive subjects with uncomplicated type 1 DM. Renal
      function and brachial artery flow-mediated vasodilatation (FMD) were measured
      before and after an intravenous infusion of the NO synthase inhibitor N(G)-nitro
      l-arginine methyl ester (l-NMMA) in 21 healthy control and 37 type 1 DM patients.
      Measurements in DM participants were made under clamped euglycemic conditions.
      The effect of l-NMMA on circulating and urinary NO metabolites (NO(x)) and cGMP
      and on urinary prostanoids was also determined. Baseline characteristics were
      similar in the two groups. For analysis, the DM patients were divided into those
      with hyperfiltration (DM-H, n = 18) and normal glomerular filtration rate (GFR)
      levels (DM-N, n = 19). Baseline urine NO(x) and cGMP were highest in DM-H. l-NMMA
      led to a decline in GFR in DM-H (152 +/- 16 to 140 +/- 11 ml.min(-1).1.73 m(-2))
      but not DM-N or healthy control participants. The decline in effective renal
      plasma flow in response to l-NMMA (806 +/- 112 to 539 +/- 80 ml.min(-1).1.73 m(
      2)) in DM-H was also exaggerated compared with the other groups (repeated
      measures ANOVA, P < 0.05), along with declines in urinary NO(x) metabolites and
      cGMP. Baseline FMD was lowest in DM-H compared with the other groups and did not
      change in response to l-NMMA. l-NMMA reduced FMD and plasma markers of NO
      bioactivity in the healthy control and DM-N groups. In patients with
      uncomplicated type 1 DM, renal hyperfiltration is associated with increased NO
      bioactivity in the kidney and reduced NO bioactivity in the systemic circulation,
      suggesting a paradoxical state of high renal and low systemic vascular NO
      bioactivity.

PMID- 22855278
TI  - Dynamic cardiac output regulation at rest, during exercise, and muscle
      metaboreflex activation: impact of congestive heart failure.
AB  - We tested whether mild and moderate dynamic exercise and muscle metaboreflex
      activation (MMA) affect dynamic baroreflex control of heart rate (HR) and cardiac
      output (CO), and the influence of stroke volume (SV) fluctuations on CO
      regulation in normal (N) and pacing-induced heart failure (HF) dogs by employing
      transfer function analyses of the relationships between spontaneous changes in
      left ventricular systolic pressure (LVSP) and HR, LVSP and CO, HR and CO, and SV
      and CO at low and high frequencies (Lo-F, 0.04-0.15 Hz; Hi-F, 0.15-0.6 Hz). In N
      dogs, both workloads significantly decreased the gains for LVSP-HR and LVSP-CO in
      Hi-F, whereas only moderate exercise also reduced the LVSP-CO gain in Lo-F. MMA
      during mild exercise further decreased the gains for LVSP-HR in both frequencies
      and for LVSP-CO in Lo-F. MMA during moderate exercise further reduced LVSP-HR
      gain in Lo-F. Coherence for HR-CO in Hi-F was decreased by exercise and MMA,
      whereas that in Lo-F was sustained at a high level (>0.8) in all settings. HF
      significantly decreased dynamic HR and CO regulation in all situations. In HF,
      the coherence for HR-CO in Lo-F decreased significantly in all settings; the
      coherence for SV-CO in Lo-F was significantly higher. We conclude that dynamic
      exercise and MMA reduces dynamic baroreflex control of HR and CO, and these are
      substantially impaired in HF. In N conditions, HR modulation plays a major role
      in CO regulation. In HF, influence of HR modulation wanes, and fluctuations of SV
      dominate in CO variations.

PMID- 22855279
TI  - Acute regulation of activin A and its binding protein, follistatin, in serum and
      tissues following lipopolysaccharide treatment of adult male mice.
AB  - Activin A, a member of the transforming growth factor-beta family, increases in
      the circulation within 1 h after administration of bacterial LPS. To clarify the
      origins of this rapid increase, the distribution of activin A and its binding
      protein, follistatin, and their production following LPS treatment, were assessed
      in adult male mice. In untreated mice, activin A was detectable in all 23 tissues
      examined, with highest mRNA expression (as measured by quantitative RT-PCR) was
      found in the liver, and the largest concentration of activin A protein (by ELISA)
      was found in the bone marrow. Likewise, follistatin mRNA and protein were present
      in all tissues, with highest expression in the vas deferens. Activin A and
      follistatin mRNA did not increase significantly in any tissue within the first
      hour after LPS, but activin A protein decreased by 35% in the bone marrow and
      increased 5-fold in the lung. No significant changes were observed in any other
      tissue. Activin A reached a peak in the circulation 1 h following LPS, and then
      declined. Cycloheximide, an inhibitor of protein translation, reduced this
      increase of activin A by more than 50%. Actinomycin D, an inhibitor of mRNA
      transcription, had no effect. Circulating follistatin did not increase until 4 h
      after LPS and was not affected by either inhibitor. These data indicate that the
      rapid increase in circulating activin A during LPS-induced inflammation is
      regulated at the posttranscriptional level, apparently from newly translated and
      stored protein, and implicate bone marrow-derived cells, and, in particular,
      neutrophils, as a significant source of this preformed activin A.

PMID- 22855280
TI  - Influence of exercise intensity on pulmonary oxygen uptake kinetics in young and
      late middle-aged adults.
AB  - It is unclear whether pulmonary oxygen uptake (Vo2) kinetics demonstrate linear,
      first-order behavior during supra gas exchange threshold exercise. Resolution of
      this issue is pertinent to the elucidation of the factors regulating oxygen
      uptake (Vo2) kinetics, with oxygen availability and utilization proposed as
      putative mediators. To reexamine this issue with the advantage of a relatively
      large sample size, 50 young (24 +/- 4 yr) and 15 late middle-aged (54 +/- 3 yr)
      participants completed repeated bouts of moderate and heavy exercise. Pulmonary
      gas exchange, heart rate (HR), and cardiac output (Q) variables were measured
      throughout. The phase II tau was slower during heavy exercise in both young
      (moderate: 22 +/- 9; heavy: 29 +/- 9 s; P <= 0.001) and middle-aged (moderate: 22
      +/- 9; heavy: 30 +/- 8 s; P <= 0.001) individuals. The HR tau was slower during
      heavy exercise in young (moderate: 33 +/- 10; heavy: 44 +/- 15 s; P <= 0.05) and
      middle-aged (moderate: 30 +/- 12; heavy: 50 +/- 20 s; P <= 0.05) participants,
      and the Q tau showed a similar trend (young moderate: 21 +/- 13; heavy: 28 +/- 16
      s; middle-aged moderate: 32 +/- 13; heavy: 40 +/- 15 s; P >= 0.05). There were no
      differences in primary component Vo2 kinetics between age groups, but the middle
      aged group had a significantly reduced Vo2 slow component amplitude in both
      absolute (young: 0.25 +/- 0.09; middle-aged: 0.11 +/- 0.06 l/min; P <= 0.05) and
      relative terms (young: 15 +/- 10; middle-aged: 9 +/- 4%; P <= 0.05). Thus Vo2
      kinetics do not demonstrate dynamic linearity during heavy intensity exercise.
      Speculatively, the slower phase II tau during heavy exercise might be
      attributable to reduced oxygen availability. Finally, the primary and slow
      components of Vo2 kinetics appear to be differentially influenced by middle age.

PMID- 22855282
TI  - C-N bond cleavage and ring expansion of N-heterocyclic carbenes using
      hydrosilanes.

PMID- 22855284
TI  - Someone is not listening to the facts: there is little psychiatry outside child
      and adolescent psychiatry.

PMID- 22855283
TI  - Angiographic and platelet reactivity outcomes with prasugrel 60 mg pretreatment
      and clopidogrel 600 mg pretreatment in primary percutaneous coronary
      intervention.
AB  - Pretreatment with 60 mg of prasugrel is more effective than 300 mg of clopidogrel
      in reducing thrombotic complications with primary percutaneous coronary
      intervention (PCI). We compared angiographic outcomes and platelet reactivity
      between treatment with 60 mg of prasugrel and 600 mg of clopidogrel administered
      before primary PCI. In this single centre non-randomized study, 65 consecutive
      Asian patients with ST-elevation myocardial infarction (STEMI) received 60 mg of
      prasugrel before primary PCI. The pre- and post-PCI corrected thrombolysis in
      myocardial infarction frame count (CTFC) and the 8-h post-treatment platelet
      vasodilator-stimulated phosphoprotein (VASP) index was compared with a matched
      historical Asian STEMI cohort (n = 65) receiving 600 mg of clopidogrel
      pretreatment. Comparing the prasugrel and clopidogrel groups, the mean age was
      54.1 +/- 10.2 versus 55.5 +/- 11.8 years, P = 0.238, and the mean body mass index
      was 24.6 +/- 2.0 versus 24.7 +/- 2.8 kg m(-2), P = 0.393. The mean pre-PCI CTFC
      was 82.1 +/- 30.2 versus 86.1 +/- 27.6, P = 0.045, and the mean post-PCI CTFC was
      21.1 +/- 13.9 versus 20.1 +/- 9.2, P = 0.309. Pre-PCI coronary thrombi were
      visualised in 6.3 versus 18.1 %, P = 0.038. The median VASP index was 22.2 +/-
      24.5 versus 70.5 +/- 17.5 %, P < 0.001, and high on-treatment platelet reactivity
      (VASP index > 50 %) was observed in 13.8 versus 84.3 %, P = 0.001. Rescue
      intracoronary glycoprotein inhibitors were administered to 29.7 versus 51.0 %, P
      = 0.018, respectively. Treatment with 60 mg of prasugrel before primary PCI was
      associated with lower platelet reactivity, a modest trend towards better pre-PCI
      angiographic outcomes, less pre-PCI coronary thrombi and less rescue glycoprotein
      inhibitor use compared with 600 mg of clopidogrel. The very high frequency of
      high on-clopidogrel platelet reactivity with 600 mg of clopidogrel in this Asian
      STEMI cohort deserves further study.

PMID- 22855285
TI  - Effectiveness of Modified Early Warning Score in predicting outcomes in oncology
      patients.
AB  - BACKGROUND: Patients at risk of rapid deterioration and critical illness often
      have preceding changes in physiological parameters. Track and trigger systems,
      such as the Modified Early Warning Score (MEWS) used in the UK, have been
      demonstrated to have some utility in identifying these patients particularly
      among general medical and surgical patients. AIM: Assess the effectiveness of
      MEWS and the proposed (NHS Early Warning Score) in oncology patients. Identify
      the key physiological parameters that predict outcome in this cohort. DESIGN: We
      performed a retrospective analysis at a specialist oncology hospital in the North
      West of England. METHOD: The data for 840 patients reviewed by the Outreach Team
      between April 2009 and January 2011 was analysed. The effectiveness of the MEWS
      in predicting Critical Care admission and 30 day mortality was assessed.
      Statistical analysis to identify the key physiological parameters in predicting
      these two outcomes was also performed. RESULTS: The MEWS score was statistically
      significant in predicting both outcome measures (CCU admission P = 0.037 and 30
      day mortality P = 0.004). Respiratory rate (P = 0.0003/P = 0.0001) and
      temperature (P = 0.033/P <= 0.0001) were the key physiological variables in
      predicting clinical deterioration. Blood pressure (P = 0.999/P = 0.619) and pulse
      rate (P = 0.446/P = 0.051) did not have statistical significance in predicting
      either outcome. However, analysis of receiver operator curves showed that MEWS
      had poor value in predicting both outcomes (0.55 and 0.6, respectively).
      CONCLUSION: The currently used track and trigger systems have poor discriminatory
      value in identifying Oncological patients at risk of deterioration. An adapted
      score more focused upon the key predictive physiological parameters in this
      population needs to be developed to produce a more effective tool.

PMID- 22855286
TI  - Back to the future: renal tubular acidosis then and now.

PMID- 22855287
TI  - Hypopituitarism, pulmonary infiltration and a spontaneously resolving occipital
      mass.

PMID- 22855288
TI  - Emphysematous cystitis.

PMID- 22855289
TI  - A fast collapsed data method for estimating haplotype frequencies from pooled
      genotype data with applications to the study of rare variants.
AB  - Haplotype information could lead to more powerful tests of genetic association
      than single-locus analyses but it is not easy to estimate haplotype frequencies
      from genotype data due to phase ambiguity. The challenge is compounded when
      individuals are pooled together to save costs or to increase sample size, which
      is crucial in the study of rare variants. Existing expectation-maximization type
      algorithms are slow and cannot cope with large pool size or long haplotypes. We
      show that by collapsing the total allele frequencies of each pool suitably, the
      maximum likelihood estimates of haplotype frequencies based on the collapsed data
      can be calculated very quickly regardless of pool size and haplotype length. We
      provide a running time analysis to demonstrate the considerable savings in time
      that the collapsed data method can bring. The method is particularly well suited
      to estimating certain union probabilities useful in the study of rare variants.
      We provide theoretical and empirical evidence to suggest that the proposed
      estimation method will not suffer much loss in efficiency if the variants are
      rare. We use the method to analyze re-sequencing data collected from a case
      control study involving 148 obese persons and 150 controls. Focusing on a region
      containing 25 rare variants around the MGLL gene, our method selects three rare
      variants as potentially causal. This is more parsimonious than the 12 variants
      selected by a recently proposed covering method. From another set of 32 rare
      variants around the FAAH gene, we discover an interesting potential interaction
      between two of them.

PMID- 22855290
TI  - Is use of PPIs related to increased intraepithelial lymphocytes in the colon?
AB  - BACKGROUND: The use of proton pump inhibitors (PPIs) is thought to increase the
      incidence of microscopic colitis (MC), although the exact mechanisms are not
      fully understood. Increased infiltration of intraepithelial lymphocytes (IELs) is
      a pathologic finding of MC (including collagenous or lymphocytic colitis). AIMS:
      We investigated whether PPI use is associated with increased IEL infiltration and
      inflammation in the lamina propria. METHODS: We retrospectively reviewed the
      medical records and histological reports of 78 patients receiving PPIs who had no
      symptoms of diarrhea, and their age- and gender- matched controls. The levels of
      IELs and inflammation in the lamina propria were assessed independently by two
      pathologists using H&E and immunohistochemical staining for CD3 and CD8. RESULTS:
      The IEL count was significantly higher in the PPI group than in controls (12.92
      +/- 6.27 vs. 8.10 +/- 4.21 per 100 epithelial cells, p < 0.001), as was the
      extent of inflammation (1.74 +/- 0.90 vs. 0.86 +/- 0.78, p < 0.001). PPI use was
      associated with increased IEL infiltration in a multivariate analysis (OR, 3.232;
      95 % CI, 1.631-6.404, p < 0.001). Within the PPI group, however, the IEL count
      was not significantly associated with gender, age, type of PPI, or duration of
      PPI use. CONCLUSIONS: The use of PPIs has a significant association with
      increased IEL infiltration for subjects without symptoms of diarrhea. This
      finding suggests that changes such histological alterations seen in the early
      phage seen in MC possibly represent the stage of the disease even before the
      onset of symptoms.

PMID- 22855291
TI  - The role of 5-HTT LPR and GNbeta3 825C>T polymorphisms and gene-environment
      interactions in irritable bowel syndrome (IBS).
AB  - BACKGROUND: Smaller studies have evaluated SLC6A4 5-HTTLPR and GNbeta3 825C>T
      polymorphisms in IBS, and interactions between 5-HTT LPR with life events have
      been reported in the psychiatric literature, but gene-environment studies in IBS
      are lacking. AIMS: The purpose of this study was to assess the association of two
      polymorphisms with IBS and age of onset, and whether there are gene-environment
      interactions with IBS. METHODS: Outpatients with IBS and controls completed a
      validated questionnaire and provided blood for DNA. Comparisons of
      genotype/allele frequencies between cases and controls were performed with
      logistic regression. Linear regression was used to evaluate the association
      between the variants and age of onset. Environmental variables tested included
      abuse, parental alcohol abuse, parental psychiatric disorders, and
      gastrointestinal infections. RESULTS: Genotyping was performed in 385 cases and
      262 controls with median age of 50 years (range, 18.0-70.0) and 498 (77 %)
      females. The IBS subtype distribution among cases was: 102 (26 %) D-IBS, 40 (10
      %) C-IBS, 125 (32 %) M-IBS, 118 (31 %) other. No association was observed between
      IBS or age of onset and both variants. Significant interactions were observed
      between GI infection and the GNbeta3 825T allele. For those reporting
      gastrointestinal infection, the OR for IBS was 3.9 (95 % CI 1.2-12.7) whereas the
      OR was 0.86 (95 % CI 0.65-1.13) for those without prior infection. CONCLUSIONS:
      There was a significant interaction between the GNbeta3 polymorphism and
      infection in the development of IBS, suggesting that its etiology is the result
      of a combination of specific genetic and environmental risk factors.

PMID- 22855292
TI  - Tetradecylthioacetic acid attenuates inflammation and has antioxidative potential
      during experimental colitis in rats.
AB  - BACKGROUND: The fatty acid analogue tetradecylthioacetic acid (TTA) is a moderate
      pan-activator of peroxisome proliferator-activated receptors (PPARs), and has in
      previous studies showed potential as an antioxidant and anti-inflammatory agent,
      both through PPAR and non-PPAR mediated mechanisms. AIMS: This study aimed to
      determine whether TTA could alleviate dextran sulfate sodium (DSS)-induced
      colitis in rats. METHODS: Male Wistar rats were fed a control diet (control- and
      DSS-group) or a diet supplemented with 0.4 % TTA (TTA + DSS-group) for 30 days,
      and DSS was added to the drinking water the last 7 days. Ultrasound measurements
      were performed at day 29. At day 30, rats were sacrificed and the distal colon
      was removed for histological evaluation and measurement of cytokine levels,
      oxidative damage, and gene expression. RESULTS: The disease activity index was
      not improved in the TTA + DSS-group compared to the DSS-group. However,
      ultrasound measurements showed a significantly reduced colonic wall thickening in
      the TTA + DSS-group. TNF-alpha, IL-1beta, and IL-6 were reduced at the protein
      and mRNA level in the TTA + DSS-group. Moreover, TTA-treated rats demonstrated
      reduced colonic oxidative damage, while inducible nitric oxide synthase 2 mRNA
      expression was elevated in both the DSS- and TTA + DSS-groups. PPARgamma
      signaling may be involved in the anti-inflammatory response to TTA, as Pparg mRNA
      expression was significantly upregulated in colon. CONCLUSIONS: This study
      demonstrated that the pan-PPAR agonist TTA reduced colonic oxidative damage and
      cytokine levels in a rat model of colitis, and its potential to ameliorate
      colitis should be further explored.

PMID- 22855294
TI  - Fretting about fat: a new look at the lipid droplet surface and the roundabout
      role of Plin2 in cellular lipid storage: focus on "Direct interaction of Plin2
      with lipids on the surface of lipid droplets: a live cell FRET analysis".

PMID- 22855293
TI  - Recurrent blood eosinophilia in ulcerative colitis is associated with severe
      disease and primary sclerosing cholangitis.
AB  - BACKGROUND AND AIMS: Eosinophils are implicated in the pathogenesis of
      inflammatory bowel disease (IBD). A subset of IBD patients develops blood
      eosinophilia, and the clinical profile of these patients is undefined. We sought
      to characterize IBD patients with and without eosinophilia. METHODS: We studied a
      prospective registry of 1,176 IBD patients followed in a tertiary referral
      center. Patients who developed eosinophilia at any time were identified by
      electronic medical record query. We performed a chart review case-control study
      comparing patients with recurrent eosinophilia versus randomly selected disease
      matched patients with no history of eosinophilia. Histological analysis was
      performed on selected cases and controls. RESULTS: Eosinophilia at any time was
      more prevalent in ulcerative colitis (UC) patients than Crohn's disease patients
      (22.2 versus 12.7%), as was recurrent eosinophilia (3.4 versus 0.7%). UC patients
      with recurrent eosinophilia were predominantly male compared with the control UC
      population (81.3 versus 46.9%) and had higher rates of colectomy for either
      medically refractory disease or dysplasia/cancer than control UC patients (56.3
      versus 15.6%). Primary sclerosing cholangitis (PSC) occurred in 37.5% of UC
      patients with recurrent eosinophilia compared with only 3.1% in the UC controls.
      Histological analysis of random diagnostic samples from UC patients with
      recurrent eosinophilia demonstrated a normal eosinophil pattern as seen in the
      control UC population. CONCLUSIONS: Eosinophilia-associated UC is a subgroup of
      IBD associated with severe colitis and PSC. Further studies are warranted to
      characterize molecular mechanisms underlying eosinophilia-associated UC and to
      determine optimal approaches for therapy.

PMID- 22855295
TI  - Regulation of endothelial cell morphogenesis by the protein kinase D
      (PKD)/glycogen synthase kinase 3 (GSK3)beta pathway.
AB  - Vascular morphogenesis is a key process for development, reproduction, and
      pathogenesis. Thus understanding the mechanisms of this process is of
      pathophysiological importance. Despite the fact that collagen I is the most
      abundant and potent promorphogenic molecule known, the molecular mechanisms by
      which this protein regulates endothelial cell tube morphogenesis are still
      unclear. Here we provide strong evidence that collagen I induces tube
      morphogenesis by inhibiting glycogen synthase kinase 3beta (GSK3beta). Further
      mechanistic studies revealed that GSK3beta activity is regulated by protein
      kinase D (PKD). PKD inhibited GSK3beta activity, which was required for collagen
      I-induced endothelial tube morphogenesis. We also found that GSK3beta regulated
      trafficking of integrin alpha(2)beta(1) in a Rab11-dependent manner. Taken
      together, our studies highlight the important role of PKD in the regulation of
      collagen I-induced vascular morphogenesis and show that it is mediated by the
      modulation of GSK3beta activity and integrin alpha(2)beta(1) trafficking.

PMID- 22855296
TI  - Managing macrophages in rheumatoid arthritis by reform or removal.
AB  - Macrophages play a central role in the pathogenesis of rheumatoid arthritis (RA).
      There is an imbalance of inflammatory and antiinflammatory macrophages in RA
      synovium. Although the polarization and heterogeneity of macrophages in RA have
      not been fully uncovered, the identity of macrophages in RA can potentially be
      defined by their products, including the co-stimulatory molecules, scavenger
      receptors, different cytokines/chemokines and receptors, and transcription
      factors. In the last decade, efforts to understand the polarization, apoptosis
      regulation, and novel signaling pathways in macrophages, as well as how distinct
      activated macrophages influence disease progression, have led to strategies that
      target macrophages with varied specificity and selectivity. Major targets that
      are related to macrophage development and apoptosis include TNF-alpha, IL-1, IL
      6, GM-CSF, M-CSF, death receptor 5 (DR5), Fas, and others, as listed in Table 1.
      Combined data from clinical, preclinical, and animal studies of inhibitors of
      these targets have provided valuable insights into their roles in the disease
      progression and, subsequently, have led to the evolving therapeutic paradigms in
      RA. In this review, we propose that reestablishment of macrophage equilibrium by
      inhibiting the development of, and/or eliminating, the proinflammatory
      macrophages will be an effective therapeutic approach for RA and other autoimmune
      diseases.

PMID- 22855298
TI  - Comparison of national mental health quality assessment programs across the
      globe.
AB  - OBJECTIVE: This study by the International Initiative for Mental Health
      Leadership Clinical Leaders Project sought to describe ongoing or soon-to-be
      established national-level mental health quality measurement programs in 12
      participating countries, in order to understand the nature and structure of these
      programs. METHODS: A survey was distributed to representatives from the
      participating countries (Australia, Canada, England, Germany, Ireland, Japan, the
      Netherlands, New Zealand, Norway, Scotland, Taiwan, and the United States). Data
      included descriptions of qualifying programs and the organizations responsible
      for them, quality indicators used, entities assessed, sources and means of the
      programs' data collection, the level at which data are reported, and how the data
      are used. Participants were asked to identify which quality domains and
      subdomains were represented by indicators in each program. Results were analyzed
      with descriptive statistics. RESULTS: Thirty-eight programs were identified. Most
      programs were administered by governmental organizations, focused on hospital
      care, and used encounter or utilization databases as sources of information.
      Programs used different methods to identify indicators. Program data were used
      for various purposes. A wide range of domains of quality were represented in the
      programs reported, although most commonality was seen in domains associated with
      high-acuity care, with fewer programs assessing recovery-related domains.
      CONCLUSIONS: This study found wide variation among established quality assessment
      programs, which may reflect a focus on local priorities. The goal of this project
      is to work toward establishing an international framework for mental health
      quality assessment and thus a means to compare key measures of performance across
      countries.

PMID- 22855299
TI  - Design and synthesis of novel 3-(4-chlorophenyl)-2-(3-substituted propyl thio)
      quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents.
AB  - A series of novel 3-(4-chlorophenyl)-2-(3-substituted propyl) quinazolin-4-(3H)
      ones have been synthesized and tested for their in vivo H1-antihistaminic
      activity on conscious guinea pigs. All the test compounds have protected the
      animals from histamine induced bronchospasm significantly. Compound 3-(4
      chlorophenyl)-2-(3-(4-methylpiperazin-1-yl) propylthio) quinazolin-4(3H)-one
      (PC5) emerged as the most active compound (77.53% protection) of the series when
      compared to the reference standard chlorpheniramine maleate (70.09% protection).
      Compound PC5 shows negligible sedation (6.16%) compared to chlorpheniramine
      maleate (29.58%). Therefore, compound PC5 can serve as the lead molecule for
      further development into a new class of H1-antihistaminic agents.

PMID- 22855297
TI  - Biologic therapies for spondyloarthritis: what is new?
AB  - The course of axial spondyloarthritis (axSpA), including ankylosing spondylitis
      (AS), is strongly influenced by the degree of disease activity over time, which
      is mainly based on inflammation, and by the impairment of function, which is
      based on structural damage-mainly, new bone formation-and inflammation. In AS,
      nonsteroidal anti-inflammatory agents are currently recommended as the first
      choice of medical therapy, and there is also a clear role for regular exercise
      and physiotherapy in order to preserve and prevent loss of spinal mobility. For
      patients who have insufficiently responded to conventional medications, there are
      now four biologics approved for the treatment of patients with active AS in many
      countries, all directed against TNFalpha: infliximab, etanercept, adalimumab, and
      golimumab; studies with certolizumab are currently ongoing. Several studies with
      patients classified as nonradiographic axSpA have also shown a good response to
      TNF blockers; in patients with early disease and high CRP levels, the response
      rates were even better. Long-term studies with TNF blockers have shown declining
      retention rates over time but sustained clinical efficacy in the patients who
      remained on treatment. States of drug-free remission are rarely reached and only
      for relatively short periods of time. More studies including magnetic resonance
      imaging (MRI) are needed to further examine the lack of effect of anti-TNF
      treatment on radiographic progression in the axial skeleton. Whether the effect
      of an early intervention with biologics will prevent the development of bone
      growth in patients with nonradiographic axial SpA remains to be seen. Biologics
      other than TNF blockers are currently not recommended for the treatment of
      patients with axSpA, because of insufficient evidence of clinically relevant
      efficacy. The anti-IL-17a antibody secukinumab may be efficacious, on the basis
      of a proof-of-concept trial. Finally, first data on biosimilars of TNF blockers
      have recently been presented.

PMID- 22855300
TI  - Paracetamol (acetaminophen) - a popular and widely used nonopioid analgesic.
AB  - For several decades paracetamol has proven its clinical efficacy and safety in
      the treatment of various acute and chronic pain states. Whereas its
      pharmacokinetic properties (high oral bioavailability, good penetration into the
      brain, relative rapid hepatic elimination) are well known, its exact central mode
      of action remains to be elucidated. According to many international
      guidelines/recommendations paracetamol is a drug of first choice for relieving
      mild to moderate pain. It has been successfully combined with opioids for severe
      pain. Due to its cardiovascular, renal and gastrointestinal safety paracetamol
      offers several advantages vs. NSAIDs. It should be realized that the maximum
      daily dose is restricted to 4 g to avoid unnecessary hepatic complications.
      Keeping this limitation in mind paracetamol still represents a valuable first
      line agent in the pharmacological management of pain.

PMID- 22855301
TI  - DNA methylation changes between relapse and remission of minimal change nephrotic
      syndrome.
AB  - BACKGROUND: DNA methylation of gene promoters is associated with transcriptional
      inactivation. Changes in DNA methylation can lead to differences in gene
      expression levels and thereby influence disease development. We hypothesized that
      epigenetics underlies the pathogenesis of minimal change nephrotic syndrome
      (MCNS). METHODS: Genome-wide DNA methylation changes between relapse and
      remission in monocytes (n = 6) and naive T helper cells (Th0s) (n = 4) isolated
      from patients with MCNS were investigated using the microarray-based integrated
      analysis of methylation by isochizomers (MIAMI) method. We confirmed the MIAMI
      results using bisulfite-pyrosequencing analysis. Expression analysis was
      performed using quantitative real-time PCR. RESULTS: Three gene loci (GATA2,
      PBX4, and NYX) were significantly less methylated in Th0s during relapse than in
      remission, compared to none in monocytes. In addition, the distance distribution
      from the regression line of all probes in MIAMI was significantly different
      between monocytes and Th0s. The mRNA levels of the three genes in Th0s were not
      significantly different between relapse and remission. CONCLUSIONS: Our results
      demonstrate that the change in DNA methylation patterns from remission to relapse
      in MCNS occurs predominantly in Th0s rather than in monocytes and suggest that
      epigenetic regulation in Th0s underlies the pathogenesis of MCNS.

PMID- 22855302
TI  - Safety profile assessment of buflomedil: an overview of adverse reactions between
      1975 and 2011.
AB  - PURPOSE: Review all the individualized cases of adverse drug reaction (ADR)
      potentially related to buflomedil, a vasodilator with the indication for
      peripheral arterial disease (PAD), marketed in Europe since the 1970s but
      recently suspended by the European Medicines Agency. METHODS: A review of all
      available individualised case safety data relating to oral buflomedil from the
      buflomedil global safety database (provided by the manufacturer of buflomedil),
      the worldwide published medical literature, toxicology/poison centres and
      regulatory authorities. RESULTS: The main ADRs reported were in the
      cardiovascular (CVS) and nervous systems (NS), grouped under four (MedDRA) System
      Organ Classes (SOCs): (i) Cardiac disorders; (ii) Vascular disorders; (iii)
      Investigations; (iv) NS disorders. From an initial cumulative number of 1054 case
      reports, there were 401 cases of intentional overdose (IOD) of which 63 were
      fatal, and 137 cases of accidental overdose, with two fatalities, and 516 case
      reports of ADRs under normal conditions of use of the product at normal
      therapeutic dosage with 11 fatalities. Overdosage (intentional or accidental)
      represented 50.9% of cases, with 47.6% of patients <40 years of age. The
      indications for which these young patients were prescribed buflomedil were not
      reported in most cases. CONCLUSIONS: The main indication of buflomedil is PAD;
      however, because most cases of IOD occurred in people <40 years of age, where PAD
      is unlikely, it is possible that buflomedil was prescribed for other indications
      and/or that it was not directly prescribed to the end user, who rather gained
      access to the medication prescribed to family members or friends.

PMID- 22855304
TI  - Heart rate variability and plasma norepinephrine concentration in diabetic dogs
      at rest.
AB  - Cardiac autonomic neuropathy in dogs with diabetic mellitus (DM) was evaluated
      using measurement of heart rate variability (HRV) and plasma norepinephrine (NE)
      concentration. Dogs were divided into 2 groups; the control non-DM group (n = 13)
      and the diabetic group (n = 22) which was further divided into the well
      controlled DM (n = 11) and the poorly-controlled DM subgroups (n = 11) according
      to their fasting plasma fructosamine concentrations. The electrocardiogram (ECG)
      was recorded continuously for at least 30 min to yield HRV. The results showed
      that in the poorly-controlled DM subgroup, the average of normal R-R interval
      (mean N-N), SD of the mean of all 5-min segments of normal RR intervals (SDANN)
      were lower than the control group while heart rate was higher (P < 0.05). The
      NNA, SDNN, SDNN index and pNN50% were significantly lower when compared with the
      well-controlled DM subgroup (P < 0.05). The high frequency (HF) and total power
      were significantly lower while the ratio of low to high frequency (LF/HF) was
      higher (P < 0.05) when compared with the well-controlled DM subgroup. Moreover,
      in the poorly-controlled DM subgroup, plasma NE concentration was lower than the
      control group (210 +/- 37 vs. 479 +/- 74 pg/ml, P < 0.05). There was a
      significantly negative correlation between plasma NE and plasma fructosamine
      concentrations. It is concluded that cardiac autonomic neuropathy occurred in
      poorly-controlled DM dogs. The sympathetic activity was suppressed as shown by
      decrease in both plasma NE concentration and LF component.

PMID- 22855305
TI  - Effect of dietary cadmium and/or lead on histopathological changes in the kidneys
      and liver of bank voles Myodes glareolus kept in different group densities.
AB  - Bank voles free living in a contaminated environment are known to be more
      sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under
      laboratory conditions, but the reasons for this difference are poorly defined.
      The present work was designed to determine whether dietary lead (Pb), a common
      environmental co-contaminant, and/or animal density that affects various
      physiological processes, would influence susceptibility to Cd toxicity in the
      kidneys and liver of these animals. For 6 weeks, the female bank voles were kept
      individually or in a group of six and provided with diet containing
      environmentally relevant concentrations of Cd [<0.1 MUg/g (control) and 60 MUg/g
      dry wt] and Pb [<0.2 MUg/g (control) and 300 MUg/g dry wt] alone or in
      combination. At the end of exposure period, histopathology and analyses of
      metallothionein, glutathione and zinc that are linked to a protective effect
      against Cd toxicity, as well as Cd, Pb, copper, iron and lipid peroxidation were
      carried out. Histopathological changes in the kidneys (a focal glomerular
      swelling and proximal tubule degeneration) and liver (a focal hepatocyte
      swelling, vacuolation and inflammation) occurred exclusively in some bank voles
      kept in a group and exposed to Cd alone (2/6) or Cd + Pb (4/6). The observed
      toxicity in grouped bank voles appeared not to be based on altered (1) tissue
      disposition of Cd and/or Pb, (2) metallothionein, glutathione and zinc
      concentrations, or (3) tissue copper, iron and lipid peroxidation. The data
      indicate that high population density in combination with environmental Pb may be
      responsible for an increased susceptibility to Cd toxicity observed in bank voles
      free living in a contaminated environment; the mechanism by which animal density
      affects Cd toxicity deserves further study.

PMID- 22855306
TI  - In vitro influences of TiO2 nanoparticles on barley (Hordeum vulgare L.) tissue
      culture.
AB  - In the last decades, extensive research on the effects of nano-TiO2 on plant
      systems and different microorganisms has confirmed its photocatalytic and
      antimicrobial activity. However, there is no report on its application in plant
      cell and tissue culture as well as its role in eliminating contaminating
      microorganisms in tissue culture. In this work, barley mature embryos were
      cultured in Murashige and Skoog medium with four concentrations (0, 10, 30, 60
      MUg/ml) of TiO2 suspension in four repetitions. Quantitative and qualitative
      characteristics of calli were analyzed after each subculture. Data analysis for
      calli number in the first culture and callus size in all three cultures showed
      that the effect of treatment was significant at p > 0.95. As a result,
      quantitative features such as callus color, shape, embryogenesis, etc. were
      completely similar in both control and TiO2 nanoparticle treatments; there is no
      doubt that TiO2 nanoparticles could dramatically increase callugenesis and the
      size of calli. As well, TiO2 nanoparticles are effective bactericides with an
      aseptic effect, causing no negative change in the quality of the callus. It is
      necessary to do more complementary works to identify mechanisms involved for the
      increased calli size and embryogenesis of explants in darkness.

PMID- 22855307
TI  - Pseudoaneurysm of the facial artery occurred after mandibular sagittal split
      ramus osteotomy.
AB  - INTRODUCTION: Pseudoaneurysms are caused by rupture of arteries with
      extravasation of blood. The compressed perivascular tissue forms the wall of
      aneurysmal sac. Pseudoaneurysm directly related with surgical procedure of
      sagittal split ramus osteotomy (SSRO) was reported quite rarely especially
      related with facial artery during the vertical osteotomy. CASE REPORT: SSRO was
      carried out for a 19-year-old male; the patient visited the emergency room with
      notable swelling 3 weeks after the surgery. We experienced severe intra-oral
      bleeding with surgical exploration. Angiography revealed a pseudoaneurysm of the
      right facial artery that might be related with vertical osteotomy over lateral
      cortex of the mandibular body during orthognathic surgery. This implies that the
      minor vascular trauma from vertical osteotomy of the mandibular body during the
      conventional orthognathic surgery might cause later development of
      pseudoaneurysm.

PMID- 22855308
TI  - Cementoblastoma: a case report in deciduous tooth.
AB  - BACKGROUND: The benign cementoblastoma is an odontogenic tumor originated from
      neoplastic cementoblasts, a rare lesion mainly associated to impacted and
      deciduous teeth. It affects mostly young people with an average age of 20 years
      old, and its preferred location is in the posterior region of the mandible; the
      lesion will present itself fused both radiologically and microscopically to a
      root of an erupted permanent tooth, and the anatomopathological diagnosis is
      obtained through the analysis of the piece sent together with the involved dental
      element. CASE REPORT: The present study presents a case of cementoblastoma in the
      mandible involving the second deciduous molar tooth and preventing the eruption
      of the premolar tooth in a girl aged 11 years old. DISCUSSION: This report
      discusses relevant aspects concerning clinical, radiographic, and
      histopathological characteristics and treatments.

PMID- 22855309
TI  - Response properties of temporomandibular joint mechanosensitive neurons in the
      trigeminal sensory complex of the rabbit.
AB  - The neurophysiological properties of neurons sensitive to TMJ movement (TMJ
      neurons) in the trigeminal sensory complex (Vcomp) during passive movement of the
      isolated condyle were examined in 46 rabbits. Discharges of TMJ neurons from the
      rostral part of the Vcomp were recorded with a microelectrode when the isolated
      condyle was moved manually and with a computer-regulated mechanostimulator. A
      total of 443 neurons responding to mechanical stimulation of the face and oral
      cavity were recorded from the brainstem. Twenty-one TMJ neurons were detected
      rostrocaudally from the dorsal part of the trigeminal principal sensory nucleus
      (NVsnpr), subnucleus oralis of the trigeminal spinal nucleus, and reticular
      formation surrounding the trigeminal motor nucleus. Most of the TMJ neurons were
      located in the dorso-rostral part of the NVsnpr. Of the TMJ units recorded, 90 %
      were slowly adapting and 26 % had an accompanying resting discharge. The majority
      (86 %) of the TMJ units responded to the movement of the isolated condyle in the
      anterior and/or ventral directions, and half were sensitive to the condyle
      movement in a single direction. The discharge frequencies of TMJ units increased
      as the condyle displacement and constant velocity (5 mm/s) increased within a 5
      mm anterior displacement of the isolated condyle. Based on these results, we
      conclude that sensory information is processed by TMJ neurons encoding at least
      joint position and displacement in the physiological range of mandibular
      displacement.

PMID- 22855310
TI  - Use of a chlorhexidine-impregnated patch does not decrease the incidence of
      bacterial colonization of femoral nerve catheters: a randomized trial.
AB  - PURPOSE: Femoral nerve catheter (FNC) insertion is commonly performed for
      postoperative analgesia following total knee arthroplasty (TKA). A wide range of
      rates has been reported relating to the bacterial colonization of catheters
      complicating FNC insertion. The BIOPATCH(r) is a chlorhexidine (CHG) impregnated
      patch designed to inhibit bacterial growth for days. The BIOPATCH has proven to
      be effective at decreasing bacterial colonization in epidural and vascular
      catheters. We hypothesized that the BIOPATCH would be effective at decreasing the
      rates of FNC bacterial colonization. METHODS: Following Institutional Review
      Board approval and written informed consent, 100 patients scheduled for TKA were
      prospectively enrolled in the study. Patients at elevated risk for infection were
      excluded from analysis. Femoral nerve catheters were inserted and tunneled under
      sterile conditions using ultrasound guidance following CHG skin cleansing.
      Participants were then randomized either to have the BIOPATCH applied to the
      catheter exit site or not to have the patch applied. All patients received
      pre/postoperative antibiotic therapy. The FNC tip and catheter exit site were
      cultured for bacterial growth at the conclusion of therapy. RESULTS: No
      differences were observed between groups in regards to catheter exit site.
      Catheter colonization was observed in three of 48 (6.3%) BIOPATCH patients and
      two of 47 (4.3%) non-BIOPATCH patients (risk ratio [RR] = 1.5; 95% confidence
      interval [CI] 0.3 to 8.4; P = 1.0). Colonization of the catheter exit site was
      observed in 12 BIOPATCH and 14 non-BIOPATCH patients (RR = 0.8; 95% CI 0.4 to
      1.6; P = 0.65). Local skin inflammation (non-BIOPATCH 10.6% vs BIOPATCH 2.1%) and
      colonization of the FNC exit site by more than one type of bacteria trended
      towards increased values in the non-BIOPATCH group. CONCLUSIONS: The baseline
      rate of bacterial colonization of FNCs is quite low in the setting of short-term
      use, CHG skin decontamination, ultrasound guidance, subcutaneous tunneling, and
      perioperative antibiotic therapy. No benefit was shown by using the BIOPATCH in
      this patient population. (ClinicalTrials.gov number: NCT01411891).

PMID- 22855311
TI  - Empirical shrinkage estimator for consistency assessment of treatment effects in
      multi-regional clinical trials.
AB  - Multi-regional clinical trials have been widely used for efficient global new
      drug developments. Both a fixed-effect model and a random-effect model can be
      used for trial design and data analysis of a multi-regional clinical trial. In
      this paper, we first compare these two models in terms of the required sample
      size, type I error rate control, and the interpretability of trial results. We
      then apply the empirical shrinkage estimation approach based on the random-effect
      model to two criteria of consistency assessment of treatment effects across
      regions. As demonstrated in our computations, compared with the sample estimator,
      the shrinkage estimator of the treatment effect of an individual region borrowing
      information from the other regions is much closer to the estimator of the overall
      treatment effect, has smaller variability, and therefore provides much higher
      probability for demonstrating consistency. We use a multinational trial example
      with time to event endpoint to illustrate the application of the method.

PMID- 22855312
TI  - [Quality in (acute) pain therapy: plea for a paradigm shift].

PMID- 22855314
TI  - [What Paul Sudeck already suspected: from Sudeck's disease to complex regional
      pain syndrome].

PMID- 22855313
TI  - [Quality management in acute pain therapy: results from a survey of certified
      hospitals].
AB  - AIM: Systems for and methods of quality management are increasingly being
      implemented in public health services. The aim of our study was to analyze the
      current state of the integrated quality management concept "quality management
      acute pain therapy" of the TUV Rheinland(r) (TUV) after a 5-year project period.
      MATERIAL AND METHODS: General characteristics of the participating hospitals,
      number of departments certified by the TUV and implementation of structures and
      processes according to the TUV guidelines were evaluated by a mail questionnaire.
      Furthermore, positive and negative aspects concerning the effects of
      certification were evaluated by the hospitals' representatives of certification.
      RESULTS: A total of 36 questionnaires were returned. Since 2006 the number of
      certified hospitals (2011: n = 48) and surgical departments (2011: n = 202) has
      increased continuously. The number of certified medical departments is low (2011:
      n = 39); however, in the last 3 years, it has increased by about 200-300%
      annually. Standard operative procedures for pain therapy and measurement of pain
      intensity at regular intervals were implemented in all certified clinics (100%).
      Although 41% take part in the benchmarking project QUIPS (Quality Improvement in
      Postoperative Pain Therapy), 24% do not systematically check the quality of the
      outcome of pain management. Acceptance of the new pain therapy concepts among
      nursing staff was rated positively (ratio positive:negative 16:1); however,
      acceptance among physicians was rated negatively (1:15). CONCLUSION:
      Certification by the TUV leads to sustainable implementation of quality
      management principles. Future efforts should focus on better integration of
      physicians in acute pain therapy and the development of an integrated tool to
      measure patients' outcome.

PMID- 22855315
TI  - [Pediatric caudal anesthesia: importance and aspects of safety concerns].
AB  - Caudal block is a safe procedure commonly used for pediatric perioperative
      analgesia. Complications are extremely rare but nevertheless local and systemic
      contraindications must be excluded. Optimal safety and quality result when strict
      attention is paid to technical details. A local anesthetic (LA) containing
      epinephrine allows early detection of inadvertent intravascular LA
      administration; therefore an epinephrine/LA mixture is recommended at least for
      the test dose. In terms of safety the choice of LA itself is probably of
      secondary importance. Clonidine as an adjuvant has an excellent risk/benefit
      profile with minimal side effects. Inadvertent systemic LA intoxication is a rare
      but potentially fatal complication of regional anesthesia and measures for
      prevention and early detection are essential. Should circulatory arrest occur,
      immediate resuscitation following standard guidelines is to be initiated
      including the use of epinephrine as the first line drug. Intravenous
      administration of lipid solutions may be beneficial as a secondary adjunct to
      stabilize hemodynamics but is not an alternative to epinephrine.

PMID- 22855318
TI  - Treatment of complex intracranial aneurysms with a telescoping stent technique.
AB  - BACKGROUND AND OBJECT: Complex intracranial aneurysms present a treatment
      challenge for both open and endovascular modalities of treatment. This report
      seeks to illustrate a series of patients with aneurysms treated with telescoping
      stents as a method of flow diversion for small and fusiform intracranial
      aneurysms. MATERIAL AND METHODS: A retrospective evaluation of six patients
      treated with a telescoping stent technique utilizing available stents (at that
      time before the pipeline era) for complex cerebral aneurysms between January 2009
      and January 2010 was performed. Five patients had dissecting aneurysms and one
      patient had a small superior hypophyseal artery aneurysm. One of the patients was
      treated in the setting of a Hunt and Hess grade IV subarachnoid hemorrhage.
      Follow-up cerebral angiography was performed postprocedure at 6 months. RESULTS:
      At a mean follow-up period of 9 months, all the patients experienced complete or
      near-complete occlusion (>95%). No periprocedural complications were noted in
      this series. No episodes of hemorrhage or thromboembolic complications occurred.
      CONCLUSIONS: Overlapping Neuroform and Enterprise stents may induce complete
      thrombosis of intracranial aneurysms and facilitate parent artery remodeling. The
      use of self-expanding stents is still an adequate treatment modality, especially
      if there is a need for vessel wall stabilization rather than flow diversion. The
      technique is also a sufficient alternative in small intracranial aneurysms not
      readily amenable to open surgical treatment or traditional endovascular coil
      embolization.

PMID- 22855319
TI  - Cerebrospinal fluid leaks after planned intradural spine surgery: a single-center
      analysis of 91 cases.
AB  - BACKGROUND AND STUDY OBJECT: A leak-proof dura closure after elective surgery for
      intradural spinal lesions is important to achieve an uncomplicated postoperative
      course. Because many different closure techniques and dura substitutes exist, we
      tried to identify the superior material and technique to avoid cerebrospinal
      fluid leaks (CSFLs). PATIENTS AND METHODS: Between 2004 and 2009, 91 patients
      underwent surgical treatment of intradural spinal pathologies with primary dura
      closure with or without the use of dura substitutes at our institution. Pre- and
      postoperative images and the clinical course were analyzed retrospectively with
      respect to the occurrence of CSFL. RESULTS: In 34% of the 91 patients,
      radiological signs of CSFL were observed. A total of 12 patients (13%) were
      symptomatic for CSFL and required a single puncture, lumbar drain, or surgical
      revision. No significant relation between CSFL and patient characteristics,
      underlying diagnosis, localization, or extension was noted. In contrast, the
      incidence of CSFL was significantly increased if more than one substitute for
      dura closure was used. The results showed that 41.7% of these patients showed
      radiological signs of CSFL as compared with 10.4% of patients in which only a
      single material was used. CONCLUSION: In our study, none of the applied products
      appeared to be superior to the others. Surgery with the combined use of multiple
      dura closure substitutes was associated with the enhanced incidence of
      postoperative CSFL. However, our findings concerning the various dura sealants
      could not be used to compare those different materials, due to the great variety
      of combinations of dura sealants and the retrospective analysis of the data.

PMID- 22855320
TI  - Surgery of cavernous hemangioma of the optic nerve: case report and review.
AB  - A case of a cavernous hemangioma of the optic nerve is presented. Cavernous
      malformations of the cranial nerves are quite rare and have been reported to
      involve the third nerve, the seventh nerve in the temporal bone, the seventh and
      the eighth nerves in the internal auditory canal as well as the optic chiasm and
      optic nerve. We present a case of a patient with a cavernous hemangioma within
      the right optic nerve, which could be removed by microsurgery with preservation
      and improvement of vision. Literature on this rare location of cavernoma is
      reviewed. 

PMID- 22855321
TI  - Transcranial microsurgical and endoscopic endonasal cavernous sinus (CS) anatomy:
      a cadaveric study.
AB  - AIMS AND OBJECTIVES: Even in the era of tremendous microneurosurgical and
      endoscopic development, the cavernous sinus (CS) is a challenging anatomical site
      for a neurosurgeon. Many transcranial and a few endoscopic cadaveric studies have
      been done to study the CS; probably none were undertaken to study its
      microsurgical and endoscopic anatomy side by side. In this cadaveric study we
      perform a side-by-side comparison of the microsurgical and endoscopic anatomy of
      the CS that can help neurosurgeons deal with CS lesions more efficiently.
      MATERIALS AND METHOD: Sixteen fresh cadaveric heads were studied after
      dissection. Six heads were dissected for transcranial study and six for
      endoscopic study of CS. During the transcranial study, the supratentorial brain
      was removed in three heads and CS and related anatomical structures were
      dissected. In the remaining heads, the CS was studied by keeping the brains in
      situ. In four heads both transcranial and endoscopic study was done
      simultaneously. Following dissection, microsurgical and endoscopic anatomy of CS
      was studied. RESULT: The CS and related anatomical structures were dissected
      sequentially in all cases (transcranially in 10 [6 + 4] heads; endoscopically in
      10 [6 + 4] heads), and their relationship was studied. CONCLUSION: Microscopic
      and endoscopic exposure of the CS is relatively easy in cadavers. But endoscopic
      or microsurgical exposure of the CS during surgery is more difficult requiring
      skill. With experience of the cadaveric study , the CS may be explored via
      transcranial microsurgery, endonasal endoscopy, or both simultaneously, according
      to the nature and extension of the pathology.

PMID- 22855323
TI  - Targeted delayed scanning at CT urography: a worthwhile use of radiation?
AB  - PURPOSE: To determine whether ureteral segments not filled with contrast material
      at computed tomographic (CT) urography ever contain tumor detectable only by
      filling these segments with contrast material. MATERIALS AND METHODS: In this
      institutional review board-approved, HIPAA-compliant retrospective study, with
      waiver of informed consent, databases were searched for all patients who
      underwent heminephroureterectomy or ureteroscopy between January 1, 2001, and
      December 31, 2009, with available CT urography findings in the 12 months prior to
      surgery or biopsy and patients who had undergone at least two CT urography
      procedures with a minimum 5-year follow-up between studies. One of two
      radiologists blinded to results of pathologic examination recorded location of
      unfilled segments, time of scan, subsequent filling, and pathologic or 5-year
      follow-up CT urography results. Tumors were considered missed in an unfilled
      segment if tumor was found at pathologic examination or follow-up CT urography in
      the same one-third of the ureter and there were no secondary signs of a mass with
      other index CT urography sequences. Estimated radiation dose for additional
      delayed sequences was calculated with a 32-cm phantom. RESULTS: In 59 male and 33
      female patients (mean age, 66 years) undergoing heminephroureterectomy, 27 tumors
      were present in 41 partially nonopacified ureters in 20 patients. Six tumors were
      present in nonopacified segments (one multifocal, none bilateral); all were
      identifiable by means of secondary signs present with earlier sequences. Among
      182 lesions biopsied at ureteroscopy in 124 male and 53 female patients (mean
      age, 69 years), 28 tumors were present in nonopacified segments in 25 patients
      (four multifocal, none bilateral), all with secondary imaging signs detectable
      without delayed scanning. In 64 male and 29 female patients (mean age, 69 years)
      who underwent 5-year follow-up CT urography, three new tumors were revealed in
      three patients; none occurred in the unfilled ureter at index CT urography.
      Estimated radiation dose from additional sequences was 4.3 mSv per patient.
      CONCLUSION: Targeted delayed scanning at CT urography yielded no additional
      ureteral tumors and resulted in additional radiation exposure.

PMID- 22855322
TI  - Evaluation of the association of prostate cancer-specific anxiety with sexual
      function, depression and cancer aggressiveness in men 1 year following surgical
      treatment for localized prostate cancer.
AB  - BACKGROUND: Cancer-specific anxiety (CSA) can affect treatment decisions and is
      common in men following surgery for prostate cancer (PCa). We hypothesized that
      CSA is also associated with factors affecting quality of life. Herein, we examine
      the association of CSA with psychosocial factors and PCa aggressiveness in a
      cohort of men 1 year after prostatectomy for localized PCa. METHODS: From our
      prospective PCa Registry, we identified 365 men who underwent prostatectomy for
      localized PCa who completed the Memorial Anxiety Scale for Prostate Cancer (MAX
      PC) and Expanded Prostate Cancer Index Composite at 1-year follow-up. We
      evaluated the association of scores on the MAX-PC with demographics,
      clinicopathologic features, sexual function, and depression scores using Wilcoxon
      Rank Sum and Kendall's tau correlation tests. RESULTS: Higher scores on the MAX
      PC (i.e., higher anxiety) are associated with younger age (p < 0.01) and non
      Caucasian race (p < 0.01). Men with higher MAX-PC scores also reported poor
      sexual satisfaction/function (p < 0.01) and increasing depressive symptoms (p <
      0.01). Finally, although higher anxiety is associated with several pathologic
      features of aggressiveness (stage, positive margins, PSA at 1 year; all p-values
      < 0.01), we noted several men with clinically indolent disease who reported
      significant anxiety. CONCLUSIONS: Our data suggest that higher levels of CSA are
      associated with poor sexual function and increased depressive symptoms 1 year
      after prostatectomy. Moreover, we noted demographic and pathologic features
      associated with higher CSA as well. If confirmed, our data support development of
      models to predict men at high risk of CSA following PCa surgery and targeted
      referral for additional counseling.

PMID- 22855324
TI  - N-acetylcysteine prevents electrical remodeling and attenuates cellular
      hypertrophy in epicardial myocytes of rats with ascending aortic stenosis.
AB  - Pressure overload is associated with cardiac hypertrophy and electrical
      remodeling. Here, we investigate the effects of the antioxidant N-acetylcysteine
      (NAC) on the cellular cardiac electrophysiology of female Sprague-Dawley rats
      with ascending aortic stenosis (AS). Rats were treated with NAC (1 g/kg body
      weight) or control solution 1 week before the intervention and in the week
      following AS or sham operation. Seven days after the operation, blood pressure
      and left ventricular pressure were measured before the heart was excised. Single
      cells were isolated from epicardial and endocardial layers of the left
      ventricular free wall and investigated using the whole-cell patch-clamp
      technique. Systolic blood pressure and left ventricular peak pressure were not
      significantly altered in the NAC group. NAC reduced the increase (p < 0.001) in
      the relative left ventricular weight (p < 0.05) as well as the increase (p <
      0.001) in cell capacitance in epicardial (p < 0.05), but not in endocardial
      myocytes of AS animals. The L-type Ca(2+) current (I (CaL)) was significantly
      increased by AS in epicardial (+19 % at 0 mV, p < 0.01) but not in endocardial
      myocytes. NAC completely prevented this increase in I (CaL) (p < 0.01). The
      current density of the transient outward K(+) current (I (to)) was not affected
      by AS or NAC. Action potential duration to 90 % repolarization was significantly
      prolonged in epicardial (p < 0.01) as well as in endocardial (p < 0.001) cells of
      AS animals. NAC prevented the AP prolongation in epicardial myocytes only (p <
      0.05). We conclude that reducing oxidative stress in pressure overload can
      prevent electrical remodeling and ameliorate hypertrophy in epicardial but not in
      endocardial myocytes.

PMID- 22855325
TI  - Insights into tris-(2-hydroxylethyl)methylammonium methylsulfate aqueous
      solutions.
AB  - We report herein a combined experimental-computational study on tris-(2
      hydroxylethyl)methylammonium methylsulfate in water solutions, as a
      representative ionic liquid of the aqueous-solution behavior of hydroxylammonium
      based ionic liquids. Relevant thermophysical properties were measured as a
      function of mixture composition and temperature. Classical molecular dynamics
      simulations were performed to infer microscopic structural features. The reported
      results for ionic liquid in water-rich solutions show that it behaves as isolated
      non-interacting ions solvated by water molecules, through well-defined solvation
      shells, exerting a disrupting effect on the water hydrogen bonding network.
      Nevertheless, as ionic liquid concentration increase, interionic association
      increases, even for diluted water solutions, evolving from the typical behavior
      of strong electrolytes in solution toward large interacting structures. For ionic
      liquid-rich mixtures, water exerts a minor disrupting effect on the fluid's
      structuring because it occupies regions around each ion (developing water-ion
      hydrogen bonds) but without significantly weakening anion-cation interactions.

PMID- 22855327
TI  - Preface: the hydra model system.
AB  - The freshwater Hydra polyp emerged as a model system in 1741 when Abraham
      Trembley not only discovered its amazing regenerative potential, but also
      demonstrated that experimental manipulations pave the way to research in biology.
      Since then, Hydra flourished as a potent and fruitful model system to help answer
      questions linked to cell and developmental biology, as such as the setting up of
      an organizer to regenerate a complex missing structure, the establishment and
      maintainance of polarity in a multicellular organism, the development of
      mathematical models to explain the robust developmental rules observed in this
      animal, the maintainance of stemness and multipotency in a highly dynamic
      environment, the plasticity of differentiated cells, to name but a few. However
      the Hydra model system is not restricted to cell and developmental biology;
      during the past 270 years it has also been heavily used to investigate the
      relationships between Hydra and its environment, opening new horizons concerning
      neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...

PMID- 22855328
TI  - Hydra, a fruitful model system for 270 years.
AB  - The discovery of Hydra regeneration by Abraham Trembley in 1744 promoted much
      scientific curiosity thanks to his clever design of experimental strategies away
      from the natural environment. Since then, this little freshwater cnidarian polyp
      flourished as a potent and fruitful model system. Here, we review some general
      biological questions that benefitted from Hydra research, such as the nature of
      embryogenesis, neurogenesis, induction by organizers, sex reversal, symbiosis,
      aging, feeding behavior, light regulation, multipotency of somatic stem cells,
      temperature-induced cell death, neuronal transdifferentiation, to cite only a
      few. To understand how phenotypes arise, theoricists also chose Hydra to model
      patterning and morphogenetic events, providing helpful concepts such as reaction
      diffusion, positional information, and autocatalysis combined with lateral
      inhibition. Indeed, throughout these past 270 years, scientists used
      transplantation and grafting experiments, together with tissue, cell and
      molecular labelings, as well as biochemical procedures, in order to establish the
      solid foundations of cell and developmental biology. Nowadays, thanks to
      transgenic, genomic and proteomic tools, Hydra remains a promising model for
      these fields, but also for addressing novel questions such as evolutionary
      mechanisms, maintenance of dynamic homeostasis, regulation of stemness, functions
      of autophagy, cell death, stress response, innate immunity, bioactive compounds
      in ecosystems, ecotoxicant sensing and science communication.

PMID- 22855326
TI  - Demographic history and genetic diversity in West Indian Coereba flaveola
      populations.
AB  - The bananaquit (Coereba flaveola) has been well studied throughout the Caribbean
      region from a phylogenetic perspective. However, data concerning the population
      genetics and long-term demography of this bird species are lacking. In this
      study, we focused on three populations within the Lesser Antilles and one on
      Puerto Rico and assessed genetic and demographic processes, using five nuclear
      and two mitochondrial markers. We found that genetic diversity of bananaquits on
      Puerto Rico exceeds that on the smaller islands (Dominica, Guadeloupe and
      Grenada); this might reflect either successive founder events from Puerto Rico to
      Grenada, or more rapid drift in smaller populations subsequent to colonization.
      Population growth rate estimates showed no evidence of rapid expansion and
      migration was indicated only between populations from the closest islands of
      Dominica and Guadeloupe. Overall, our results suggest that a "demographic
      fission" model, considering only mutation and drift, but without migration, can
      be applied to these bananaquit populations in the West Indies.

PMID- 22855329
TI  - Humidification during CPAP titration: an unresolved issue.

PMID- 22855330
TI  - Author response to "humidification during CPAP titration: an unresolved issue".

PMID- 22855331
TI  - Clinical and polysomnographic features of a large Turkish pedigree with restless
      leg syndrome and periodic limb movements.
AB  - PURPOSE: Restless leg syndrome (RLS) and periodic limb movements (PLMS) are
      common neurological diseases often associated with insomnia. A familial
      aggregation in RLS has been identified since it was first described; however,
      inheritance patterns of RLS/PLMS are poorly understood and their exact
      pathophysiology is not well-known. We have identified a Turkish pedigree with
      RLS/PLMS, which is a rare condition, in five generations of a family, including
      nine affected family members. METHODS: A detailed clinical evaluation of the
      family was conducted with the help of polysomnographic recording,
      electrophysiological findings, and biochemical parameters. RESULTS: The proband
      is a 38-year-old male member of the family who first started to show symptoms at
      the age of 29. All the patients from this family have been diagnosed with RLS,
      according to the criteria of the International RLS Study Group. Disease onset was
      early in all cases and even earlier in the younger generation. Three affected
      individuals also had PLMS on polysomnographic recordings. CONCLUSION: To our
      knowledge, this is the first Turkish family in which nine individuals in five
      generations are affected. We suggest an important effect of anticipation and
      genetic impact of the diseases and describe specific clinical features. Further
      investigation of clinical, genetic, and biochemical similarities between PLMS and
      RLS may yield important clues, adding to our understanding of the pathophysiology
      of these common diseases.

PMID- 22855332
TI  - Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon
      counterregulation during hypoglycemia in type 1 diabetes.
AB  - CONTEXT: The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon
      secretion at hyperglycemia but appears to enhance glucagon counterregulation
      during hypoglycemia in type 2 diabetes. OBJECTIVE: The objective of the
      investigation was to study whether vildagliptin also improves alpha-cell function
      in type 1 diabetes (T1D). PATIENTS AND METHODS: The study was a single-center,
      double-blind, randomized, placebo-controlled crossover study involving 28
      patients with C-peptide negative and antibody positive T1D [21 males, seven
      females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received
      vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy
      for 4 wk each. On d 28 of the respective treatment period, patients were served a
      standard meal (500 kcal) to raise the circulating incretin hormone levels
      followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter. MAIN OUTCOME
      MEASURE: The increase in plasma glucagon levels during the 30-min hypoglycemic
      clamp (min 165-195 of the test) was measured. RESULTS: During the meal, glucagon
      levels were lower with vildagliptin than with placebo (120 min area under the
      curve(glucagon) 2.4+/-0.2 vs. 2.6+/-0.2 nmol/liter*minutes, P=0.022 for between
      group difference). In contrast, during hypoglycemia, the glucagon
      counterregulation was not reduced by vildagliptin (increase in glucagon 1.5+/-1.0
      pmol/liter with vildagliptin vs. 1.7+/-0.8 pmol/liter with placebo, P=NS). In
      addition, the counterregulatory responses in epinephrine, norepinephrine,
      cortisol, and pancreatic polypeptide were not different between the treatments.
      During the 4-wk treatment period, vildagliptin reduced the mean glycosylated
      hemoglobin, whereas there was no change with placebo [between group difference
      was -3.4+/-1.0 mmol/mol (-0.32+/-0.09%; P=0.002)] from baseline of 57.9 mmol/mol
      (7.5%). CONCLUSIONS: Vildagliptin, although inhibiting glucagon secretion during
      hyperglycemia, does not compromise the glucagon counterregulatory response during
      hypoglycemia in T1D.

PMID- 22855333
TI  - The effect of vitamin D on calcium absorption in older women.
AB  - CONTEXT: Vitamin D is often recommended for use with calcium supplements to
      increase absorption. There are no systematic studies of vitamin D on calcium
      absorption that indicate what dose should be recommended. OBJECTIVE: Our
      objective was to study the effect of increasing doses of vitamin D3 on calcium
      absorption. DESIGN AND SETTING: We conducted a randomized double-blind placebo
      controlled trial at Creighton University Medical Center, Omaha, NE. PARTICIPANTS:
      Participants included 163 postmenopausal Caucasian women with vitamin D
      insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) below 20 ng/ml (50
      nmol/liter). INTERVENTION: Participants were randomized to receive one of the
      vitamin D3 doses, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d, or placebo for
      1 yr. Calcium intake was increased to 1200-1400 mg daily by giving daily calcium
      citrate. MAIN OUTCOME: We evaluated the change in calcium absorption on vitamin
      D. RESULTS: Mean serum 25OHD increased from baseline 15.6 ng/ml (39 nmol/liter)
      to 46.5 ng/ml (112 nmol/liter) in subjects randomized to the highest dose of
      vitamin D (4800 IU). Calcium absorption was more significantly related to serum
      25OHD (R2=0.50; P=0.001) than dose (R2=0.47; P=0.033). Calcium absorption of a
      100-mg dose increased from 52-58% (6 mg) over a serum 25OHD range of 20-66 ng/ml
      (50-165 nmol/liter). CONCLUSIONS: There was no evidence of a threshold for
      reduced calcium absorption in the serum 25OHD range of 10-66 ng/ml (25-165
      nmol/liter). The increase in absorbed calcium of 6% on high doses of vitamin D is
      so small that the same amount could be obtained from half a glass of milk (100
      ml) or 100 mg elemental calcium. The results challenge assumptions about the
      value of adding vitamin D to increase calcium absorption except when serum 25OHD
      is very low that is less than 10 ng/ml (25 nmol/liter).

PMID- 22855334
TI  - Sclerostin levels associated with inhibition of the Wnt/beta-catenin signaling
      and reduced bone turnover in type 2 diabetes mellitus.
AB  - CONTEXT: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone
      quality, and circulating levels of sclerostin significantly higher than non-T2DM
      controls. There are no data on the possible association of sclerostin with beta
      catenin, a key component of the Wnt/beta-catenin canonical signaling. OBJECTIVES:
      The aim of the study was to evaluate the circulating beta-catenin levels in T2DM
      patients and to analyze their relationship with sclerostin and bone turnover
      markers. DESIGN: This was a cross-sectional study. SETTING AND PATIENTS: The
      study was conducted at a clinical research center. Forty T2DM postmenopausal
      women were studied and compared with 40 healthy controls. Bone status was
      assessed by dual-energy x-ray absorptiometry measurements (bone mineral density)
      and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of
      type 1 collagen. Sclerostin and beta-catenin were evaluated by an
      immunoenzymetric assay. RESULTS: Consistent with previous reports in T2DM
      subjects, we found sclerostin levels higher and bone turnover markers lower than
      controls. In our cohort of T2DM patients, beta-catenin levels are significantly
      lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80;
      and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively;
      P=0.0002). beta-Catenin correlated negatively with sclerostin (P<0.0001) and
      positively with bone alkaline phosphatase (P=0.0030) only in T2DM patients and
      negatively with age in both groups. Eight of the 40 T2DM patients had vertebral
      fractures. CONCLUSIONS: These results show for the first time that T2DM patients
      have serum concentrations of beta-catenin lower than controls. The negative
      association of beta-catenin with sclerostin suggests a biological effect of
      increased sclerostin on the Wnt signaling, which appears impaired in T2DM.

PMID- 22855335
TI  - Association between physical activity and urinary estrogens and estrogen
      metabolites in premenopausal women.
AB  - OBJECTIVE: The objective of the study was to evaluate in premenopausal women the
      relationships of physically active and sedentary behaviors reported for adulthood
      and adolescence with a comprehensive profile of estrogen metabolism. METHODOLOGY:
      Fifteen estrogens and estrogen metabolites (jointly termed EM) were measured
      using liquid chromatography-tandem mass spectrometry in luteal phase urines from
      603 premenopausal women in the Nurses' Health Study II. Geometric means of
      individual EM, metabolic pathway groups, and pathway ratios were examined by
      level of exposure after adjustment for age, body mass index, alcohol intake,
      menstrual cycle length, and sample collection timing. RESULTS: High overall
      physical activity in adulthood (42+ metabolic equivalent h/wk vs. <3 metabolic
      equivalent h/wk) was associated with a 15% lower level of urinary estradiol
      (Ptrend=0.03) and 15% lower level of 16-hydroxylation pathway EM (Ptrend=0.03).
      Levels of 2- and 4-hydroxylation pathway EM did not differ significantly by
      physical activity. High overall activity was also positively associated with four
      ratios: 2-pathway EM to parent estrogens (Ptrend=0.05), 2-pathway catechols to
      parent estrogens (Ptrend=0.03), 2-pathway catechols to methylated 2-pathway
      catechols (Ptrend<0.01), and 2-hydroxyestrone to 16alpha-hydroxyestrone
      (Ptrend=0.01). Similar patterns of association were noted for walking and
      vigorous physical activity, but there was little evidence of associations with
      sedentary behaviors or activity during adolescence. CONCLUSIONS: High levels of
      physical activity were associated with lower levels of parent estrogens and 16
      hydroxylation pathway EM and preferential metabolism to 2-pathway catechols. The
      results of our analysis, the largest, most comprehensive examination of physical
      activity and estrogen metabolism to date, may be useful in future studies
      investigating the etiology of diseases linked to both physical activity and
      endogenous estrogen.

PMID- 22855336
TI  - Characterization of the cortisol stress response to sedation and anesthesia in
      children.
AB  - CONTEXT: The cortisol stress response to sedation and anesthesia in children is
      not well characterized. It is not clear whether it is necessary to give stress
      doses of corticosteroids to children with adrenal insufficiency undergoing
      sedated procedures. OBJECTIVE: Our objective was to describe the cortisol stress
      response to sedation and anesthesia in normal children. DESIGN, SETTING, AND
      PATIENTS: This was a prospective cohort study of 149 children ages 1 month to 17
      yr who presented for routine sedated procedures. Salivary cortisol was measured
      at baseline, every 30 min during procedures, at completion, and at recovery. MAIN
      OUTCOME MEASURES: We evaluated relative change in salivary cortisol from baseline
      for level of sedation achieved and type of procedure performed. RESULTS: In
      total, 117 patients had adequate samples collected, and 110 were included in the
      main analysis. Twenty-five percent of patients showed an increase in salivary
      cortisol greater than four times baseline, consistent with a stress response.
      Mean salivary cortisol increased more than 3-fold from baseline (3.7+/-0.4,
      P<0.001) for all patients in the study. There was no difference for change in
      cortisol when comparing by level of sedation achieved or by type of procedure
      performed. The majority of patients with a stress response had their highest
      levels in the recovery phase, after their procedure was completed. CONCLUSION:
      Sedation and anesthesia can induce a significant rise in cortisol in children.
      Additional studies should be performed to validate our results and to determine
      whether stress dosing of corticosteroids may be needed for children with adrenal
      insufficiency undergoing sedated procedures.

PMID- 22855337
TI  - Cardiometabolic correlates and heritability of fetuin-A, retinol-binding protein
      4, and fatty-acid binding protein 4 in the Framingham Heart Study.
AB  - CONTEXT: Fetuin-A, retinol-binding protein 4 (RBP4), and fatty-acid binding
      protein 4 (FABP4) are novel biomarkers that may link adiposity to insulin
      resistance and the metabolic syndrome (MetSyn). OBJECTIVE: The aim of this study
      was to investigate the correlates of these three adiposity biomarkers in a large
      community-based sample. DESIGN, SETTING, PARTICIPANTS, AND OUTCOMES: Serum
      concentrations of fetuin-A, RBP4, and FABP4 were assayed in 3658 participants of
      the Third Generation Framingham Heart Study cohort (mean age 40 yr, 54% women).
      We used multivariable regression to cross-sectionally relate biomarkers to
      insulin resistance, cardiovascular risk factors, and the MetSyn. The genetic
      contribution to inter-individual variation in biomarker levels was assessed using
      variance-components analysis. RESULTS: All three biomarkers exhibited sexual
      dimorphisms (levels higher in women for fetuin-A and FABP4 but greater in men for
      RBP4) and were associated positively with insulin resistance assessed using the
      homeostasis model, with high-sensitivity C-reactive protein, and with prevalent
      MetSyn (P<0.01 for all). The biomarkers showed distinct patterns of association
      with metabolic risk factors. RBP4 levels were correlated with body mass index
      only in unadjusted but not in adjusted models. None of the biomarkers were
      associated with prevalent diabetes in multivariable models. Circulating fetuin-A,
      RBP4, and FABP4 levels showed modest heritability, ranging from 15-44% (all
      P<0.0001). CONCLUSIONS: In our large young- to middle-aged community-based
      sample, we observed that circulating levels of fetuin-A, RBP4, and FABP4 are
      associated with insulin resistance and with distinct components of MetSyn
      consistent with the multifactorial pathogenesis of metabolic dysregulation.

PMID- 22855338
TI  - Clinical review: Current state and future perspectives in the diagnosis of
      diabetes insipidus: a clinical review.
AB  - CONTEXT: The differential diagnosis of diabetes insipidus (DI) is often
      challenging but essential, because treatment may vary substantially. This article
      analyzes the database and performance of currently used differential diagnostic
      tests for DI and discusses future perspectives for diagnostic improvement.
      EVIDENCE ACQUISITION: A review of electronic and print data comprising original
      and review articles retrieved from the PubMed or Cochrane Library database up to
      January 2012 was conducted. The search term "polyuria polydipsia syndrome" was
      cross-referenced with underlying forms of disease and associated clinical,
      diagnostic, and therapeutic MeSH terms. In addition, references from review
      articles and textbook chapters were screened for papers containing original data.
      Search results were narrowed to articles containing primary data with a
      description of criteria for the differential diagnosis of DI. EVIDENCE SYNTHESIS:
      Fifteen articles on differential diagnosis of DI were identified, mainly
      consisting of small series of patients, and mostly covering only part of the
      differential diagnostic spectrum of DI. Test protocols differed, and prospective
      validation of diagnostic criteria was consistently missing. Inconsistent data
      were reported on the diagnostic superiority of direct plasma arginine vasopressin
      determination over the indirect water deprivation test. Both test methods
      revealed limitations, especially in the differentiation of disorders with a
      milder phenotype. CONCLUSION: The available data demonstrate limitations of
      current biochemical tests for the differential diagnosis of DI, potentially
      leading to incorrect diagnosis and treatment. The newly available assay for
      copeptin, the C terminus of the vasopressin precursor, holds promise for a higher
      diagnostic specificity and simplification of the differential diagnostic protocol
      in DI.

PMID- 22855339
TI  - Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with
      severe vitamin D deficiency.
AB  - CONTEXT: Inherited forms of vitamin D deficiency are rare causes of rickets and
      to date have been traced to mutations in three genes, VDR, encoding the 1alpha,25
      dihydroxyvitamin D receptor, CYP27B1, encoding the vitamin D 1alpha-hydroxylase,
      and CYP2R1, encoding a microsomal vitamin D 25-hydroxylase. RESULTS: Multiple
      mutations have been identified in VDR and CYP27B1 in patients with rickets, and
      thus, the roles of these two genes in vitamin D metabolism are unassailable. The
      case is less clear for CYP2R1, in which only a single mutation, L99P in exon 2 of
      the gene, has been identified in Nigerian families, and because multiple enzymes
      with vitamin D 25-hydroxylase activity have been identified. Here we report
      molecular genetic studies on two siblings from a Saudi family who presented with
      classic symptoms of vitamin D deficiency. The affected offspring inherited two
      different CYP2R1 mutations (367+1, G->A; 768, iT), which are predicted to specify
      null alleles. CONCLUSION: We conclude that CYP2R1 is a major vitamin D 25
      hydroxylase that plays a fundamental role in activation of this essential
      vitamin.

PMID- 22855340
TI  - Involvement of hypothalamus autoimmunity in patients with autoimmune
      hypopituitarism: role of antibodies to hypothalamic cells.
AB  - CONTEXT: Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA)
      are usually searched for in autoimmune hypopituitarism. OBJECTIVE: Our objective
      was to search for AHA and characterize their hypothalamic target in patients with
      autoimmune hypopituitarism to clarify, on the basis of the cells stained by these
      antibodies, the occurrence of autoimmune subclinical/clinical central diabetes
      insipidus (CDI) and/or possible joint hypothalamic contribution to their
      hypopituitarism. DESIGN: We conducted a cross-sectional cohort study. PATIENTS:
      Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without
      (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in
      comparison with 20 patients with postsurgical hypopituitarism and 50 normal
      subjects. MAIN OUTCOME MEASURES: AHA by immunofluorescence and posterior
      pituitary function were evaluated; then AHA-positive sera were retested by double
      immunofluorescence to identify the hypothalamic cells targeted by AHA. RESULTS:
      AHA were detected at high titer in 12 patients in group 1 and in eight patients
      in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine
      of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive
      patients presented with subclinical/clinical CDI; in contrast, four patients with
      GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA
      targeting CRH- secreting cells. CONCLUSION: The occurrence of CDI in patients
      with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement
      rather than an expansion of the pituitary inflammatory process. To search for AVP
      antibody in these patients may help to identify those of them prone to develop an
      autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some
      patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells
      indicates that an autoimmune aggression to hypothalamus is jointly responsible
      for their hypopituitarism.

PMID- 22855341
TI  - A Mediterranean diet enriched with olive oil is associated with higher serum
      total osteocalcin levels in elderly men at high cardiovascular risk.
AB  - BACKGROUND: The intake of olive oil has been related to the prevention of
      osteoporosis in experimental and in in vitro models. Very few prospective studies
      have evaluated the effects of olive oil intake on circulating osteocalcin (OC) in
      humans. OBJECTIVE: The objective of the study was to examine the longitudinal
      effects of a low-fat control diet (n=34), a Mediterranean diet enriched with nuts
      (MedDiet+nuts, n=51), or a Mediterranean diet enriched with virgin olive oil
      (MedDiet+VOO, n=42) on circulating forms of OC and bone formation markers in
      elderly men at high cardiovascular risk. DESIGN: Longitudinal associations
      between baseline and follow-up (2 yr) measurements of total OC, undercarboxylated
      osteocalcin, C-telopeptide of type I collagen, and procollagen I N-terminal
      propeptide (P1NP) concentrations were examined in 127 elderly men randomized to
      three healthy dietary interventions. RESULTS: Baseline characteristics (age, body
      mass index, waist circumference, lipid profile, fasting insulin levels, and bone
      formation and resorption markers) were similar in all intervention groups. The
      total osteocalcin concentration increased robustly in the MedDiet+VOO group
      (P=0.007) in parallel to increased P1NP levels (P=0.01) and homeostasis model
      assessment-beta-cell function (P=0.01) but not in subjects on the MedDiet+nuts
      (P=0.32) or after the control diet (P=0.74). Interestingly, the consumption of
      olives was associated positively with both baseline total osteocalcin (r=0.23,
      P=0.02) and the 2-yr osteocalcin concentrations (r=0.21, P=0.04) in the total
      cohort. CONCLUSIONS: Consumption of a Mediterranean diet enriched with virgin
      olive oil for 2 years is associated with increased serum osteocalcin and P1NP
      concentrations, suggesting protective effects on bone.

PMID- 22855342
TI  - Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas.
AB  - CONTEXT: Genetic abnormalities, such as those of multiple endocrine neoplasia
      type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary
      (sporadic) parathyroid adenomas. OBJECTIVE: To identify genetic abnormalities in
      nonhereditary parathyroid adenomas by whole-exome sequence analysis. DESIGN:
      Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte
      DNA samples from 16 postmenopausal women without a family history of parathyroid
      tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland
      disease was cured by surgery. Somatic variants confirmed in this discovery set
      were assessed in 24 other parathyroid adenomas. RESULTS: Over 90% of targeted
      exons were captured and represented by more than 10 base reads. Analysis
      identified 212 somatic variants (median eight per tumor; range, 2-110), with the
      majority being heterozygous nonsynonymous single-nucleotide variants that
      predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in
      six of 16 (~35%) parathyroid adenomas, in association with loss of heterozygosity
      on chromosome 11. However, no other gene was mutated in more than one tumor.
      Mutations in several genes that may represent low-frequency driver mutations were
      identified, including a protection of telomeres 1 (POT1) mutation that resulted
      in exon skipping and disruption to the single-stranded DNA-binding domain, which
      may contribute to increased genomic instability and the observed high mutation
      rate in one tumor. CONCLUSIONS: Parathyroid adenomas typically harbor few somatic
      variants, consistent with their low proliferation rates. MEN1 mutation represents
      the major driver in sporadic parathyroid tumorigenesis although multiple low
      frequency driver mutations likely account for tumors not harboring somatic MEN1
      mutations.

PMID- 22855343
TI  - Excitotoxicity through NMDA receptors mediates cerebellar granule neuron
      apoptosis induced by prion protein 90-231 fragment.
AB  - Prion diseases recognize, as a unique molecular trait, the misfolding of CNS
      enriched prion protein (PrP(C)) into an aberrant isoform (PrP(Sc)). In this work,
      we characterize the in vitro toxicity of amino-terminally truncated recombinant
      PrP fragment (amino acids 90-231, PrP90-231), on rat cerebellar granule neurons
      (CGN), focusing on glutamatergic receptor activation and Ca(2+) homeostasis
      impairment. This recombinant fragment assumes a toxic conformation (PrP90
      231(TOX)) after controlled thermal denaturation (1 h at 53  degrees C) acquiring
      structural characteristics identified in PrP(Sc) (enrichment in beta-structures,
      increased hydrophobicity, partial resistance to proteinase K, and aggregation in
      amyloid fibrils). By annexin-V binding assay, and evaluation of the percentage of
      fragmented and condensed nuclei, we show that treatment with PrP90-231(TOX), used
      in pre-fibrillar aggregation state, induces CGN apoptosis. This effect was
      associated with a delayed, but sustained elevation of [Ca(2+)]i. Both CGN
      apoptosis and [Ca(2+)]i increase were not observed using PrP90-231 in PrP(C)-like
      conformation. PrP90-231(TOX) effects were significantly reduced in the presence
      of ionotropic glutamate receptor antagonists. In particular, CGN apoptosis and
      [Ca(2+)]i increase were largely reduced, although not fully abolished, by pre
      treatment with the NMDA antagonists APV and memantine, while the AMPA antagonist
      CNQX produced a lower, although still significant, effect. In conclusion, we
      report that CGN apoptosis induced by PrP90-231(TOX) correlates with a sustained
      elevation of [Ca(2+)]i mediated by the activation of NMDA and AMPA receptors.

PMID- 22855345
TI  - Poncet's disease (reactive arthritis associated with tuberculosis): retrospective
      case series and review of literature.
AB  - The primary objective of this study is to describe the demographics and clinical
      characteristics of patients with Poncet's disease (PD) in the Makkah region in
      Saudi Arabia, where tuberculosis is on the rise. The secondary objective is
      conducting a PD systematic literature review to compare our findings. We studied
      seven patients who presented with arthritis within the first 3 years from
      diagnosis of active tuberculosis in two centers in the Makkah region: King Faisal
      Specialist Hospital and King Fahad Hospital in Jeddah from January 2005 to
      December 2011. We conducted a literature review on PD in multiple
      biomedical/pharmaceutical databases up to December 2011. We detected a new
      pattern of reactive arthritis associated with tuberculosis (TB). We identified
      this as PD or tuberculous rheumatism, which is a sterile reactive arthritis that
      can emerge during any stage of acute TB infection. Seven cases of Poncet's
      disease were identified in our study. The most common presentation was
      extrapulmonary with involvement of multiple sites. Six out of seven patients
      developed arthritis after initiation of anti-TB drugs; one patient developed
      polyarthritis after completion of anti-TB medication. Asymmetrical polyarthritis
      was the most common presentation and the resolution of the arthritis was with
      symptomatic treatment and continuation of anti-TB drugs except in one case. PD
      may manifest in a variable pattern during the course of active tuberculous
      infection. Physicians should be aware of this rare complication associated with a
      common disease to prevent delay in diagnosis and initiation of appropriate
      treatment.

PMID- 22855346
TI  - What RA patients expect of their treatment--discussion over the result of our
      survey.
AB  - We conducted a survey among Japanese rheumatoid arthritis (RA) patients to better
      understand what they expect from treatment and whether there is a difference
      between expectations of biologics-treated and disease-modifying antirheumatic
      drugs (DMARDs)-treated patients. An anonymous survey was conducted with 165
      outpatients from our clinic (with informed written consent). On the survey, they
      wrote their age, gender, medical history, and commented on: (1) expectations for
      treatment, (2) disappointment with treatment, (3) experience of, and thoughts
      about switching treatments, (4) information wanted before starting a new
      treatment, (5) expectations before administration and noticeable differences
      after treatment, (6) level of satisfaction with current treatment, and (7)
      expectations of possible treatments. Patients who had never been treated with
      DMARDs were excluded from the survey. For "treatment goals before
      administration," 86 % responded with "assured efficacy," while 73 % responded
      "suppress joint destruction" or "recover from joint destruction." Also, more
      patients hoped for "long-lasting efficacy" (67 %) over "fast acting" (41 %),
      which suggests significance of the long-term improvement of QOL. Related to
      "disappointment with treatment," patients also felt anxiety over switching
      treatment for possibilities of not responding enough, or side effects. RA
      patients have high expectations for medication in terms of assured improvement of
      conditions and long-lasting efficacy of drugs, while the biggest concern was if
      they would have side effects or not, and if so, what type. The results suggest
      patients hope to have worries over switching medications dispelled. The results
      also verified those who have used biologics before have higher treatment goals
      than those who have not.

PMID- 22855347
TI  - Psycho-oncological care in certified cancer centres--a nationwide analysis in
      Germany.
AB  - BACKGROUND: Over the last few years, a nationwide voluntary certification system
      for cancer centres has been established in Germany. To qualify for certification,
      cancer centres must provide psycho-oncological care to every patient who needs
      it. The aim of this study was to find out how many patients have been treated by
      a psycho-oncologist in the certified centres. METHODS: All cancer centres in
      Germany that were re-certified in 2010 provided data documenting how many
      patients with primary cancer received at least 30 min of psycho-oncological
      consultation in 2009. RESULTS: Data from n = 456 certified cancer centres were
      available. In the centres, a total of 36,165 patients were seen by a psycho
      oncologist for at least 30 min, representing 37.3% of all patients in the
      centres. The highest percentage of patients who received psycho-oncological care
      was found in breast cancer centres (66.7%), and the lowest in prostate cancer
      centres (6.8%). Half of the patients (50.0%) in gynaecological cancer centres,
      37.7% in colon cancer centres and 25.4% in lung cancer centres received psycho
      oncological care. CONCLUSIONS: Compared with non-certified centres, the
      proportion of patients receiving psycho-oncological care in certified cancer
      centres has increased.

PMID- 22855349
TI  - Concerns about storage and application of dabigatran and rivaroxaban.

PMID- 22855348
TI  - Responsiveness to low-dose warfarin associated with genetic variants of VKORC1,
      CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population.
AB  - PURPOSE: The aim of this study was to assess the pharmacokinetics and
      pharmacodynamics of warfarin associated with genetic polymorphisms in VKORC1,
      CYP2C9, CYP2C19, and CYP4F2 in Indonesian patients treated with low-dose
      warfarin. METHODS: Genotyping of VKORC1, CYP2C9, CYP2C19, and CYP4F2 was carried
      out in 103 patients treated with a daily dose of 1-2 mg warfarin, 89 of whom were
      treated with a fixed daily dose of warfarin (1 mg). The plasma concentrations of
      S- and R-warfarin and S- and R-7-hydroxywarfarin were used as pharmacokinetic
      indices, while prothrombin time expressed as the international normalized ratio
      (PT-INR) was used as a pharmacodynamic index. RESULTS: In patients treated with a
      fixed daily dose of warfarin (1 mg), a higher PT-INR was associated with VKORC1
      1639 AA [median 1.35; interquartile range (IQR) 1.21-1.50] than with the GA
      (1.18; IQR 1.12-1.32; p < 0.01) and GG (1.02; IQR = 1.02-1.06; p < 0.01)
      polymorphisms, and with CYP2C9*1/*3 (1.63; IQR 1.45-1.85) compared to *1/*1
      (1.23; IQR  1.13-1.43; p < 0.05). The S-warfarin concentration was significantly
      higher in patients with CYP2C9*1/*3 than in those with *1/*1 (p < 0.05). With low
      dose warfarin administration, there was no significant difference in the
      concentrations of warfarin metabolites among any of the genotype variants. The
      genotype variations of CYP2C19 and CYP4F2 were not significantly associated with
      the PT-INR. CONCLUSION: For low-dose warfarin treatment, the VKORC1-1639 G > A
      and CYP2C9 genotype variations affected the pharmacokinetics and pharmacodynamics
      of warfarin, while we could not find significant effects of CYP4F2 or CYP2C19
      genotype variations on warfarin (metabolite) concentrations or PT-INR.

PMID- 22855350
TI  - The effects of daily weather variables on psychosis admissions to psychiatric
      hospitals.
AB  - Several studies have noted seasonal variations in admission rates of patients
      with psychotic illnesses. However, the changeable daily meteorological patterns
      within seasons have never been examined in any great depth in the context of
      admission rates. A handful of small studies have posed interesting questions
      regarding a potential link between psychiatric admission rates and meteorological
      variables such as environmental temperature (especially heat waves) and sunshine.
      In this study, we used simple non-parametric testing and more complex ARIMA and
      time-series regression analysis to examine whether daily meteorological patterns
      (wind speed and direction, barometric pressure, rainfall, sunshine, sunlight and
      temperature) exert an influence on admission rates for psychotic disorders across
      12 regions in Ireland. Although there were some weak but interesting trends for
      temperature, barometric pressure and sunshine, the meteorological patterns
      ultimately did not exert a clinically significant influence over admissions for
      psychosis. Further analysis is needed.

PMID- 22855351
TI  - Low-dose trichloroethylene alters cytochrome P450-2C subfamily expression in the
      developing chick heart.
AB  - Trichloroethylene (TCE) is an organic solvent and common environmental
      contaminant. TCE exposure is associated with heart defects in humans and animal
      models. Primary metabolism of TCE in adult rodent models is by specific hepatic
      cytochrome P450 enzymes (Lash et al. in Environ Health Perspect 108:177-200,
      2000). As association of TCE exposure with cardiac defects is in exposed embryos
      prior to normal liver development, we investigated metabolism of TCE in the early
      embryo. Developing chick embryos were dosed in ovo with environmentally relevant
      doses of TCE (8 and 800 ppb) and RNA was extracted from cardiac and extra-cardiac
      tissue (whole embryo without heart). Real-time PCR showed upregulation of CYP2H1
      transcripts in response to TCE exposure in the heart. No detectable cytochrome
      expression was found in extra-cardiac tissue. As seen previously, the dose
      response was non-monotonic and 8 ppb elicited stronger upregulation than 800 ppb.
      Immunostaining for CYP2C subfamily expression confirmed protein expression and
      showed localization in both myocardium and endothelium. TCE exposure increased
      protein expression in both tissues. These data demonstrate that the earliest
      embryonic expression of phase I detoxification enzymes is in the developing
      heart. Expression of these CYPs is likely to be relevant to the susceptibility of
      the developing heart to environmental teratogens.

PMID- 22855352
TI  - Molecular organization of various collagen fragments as revealed by atomic force
      microscopy and diffusion-ordered NMR spectroscopy.
AB  - Heterogeneous mixtures of collagen fragments can be used as nutrition supplement
      or as key ingredients for ointments with therapeutic relevance in wound healing.
      Some mixtures of collagen fragments are referred to as collagen hydrolysates
      owing to the production process with hydrolytic enzymes. Since the precise
      composition of collagen hydrolysates is generally unknown, it is of interest to
      analyze samples containing various collagen fragments with appropriate
      biophysical methods. Any product optimization without a profound knowledge
      concerning the size and the molecular weight distribution of its components is
      nearly impossible. It turned out that a combination of AFM methods with NMR
      techniques is exceptionally suited to examine the size range and the aggregation
      behavior of the collagen fragments in the hydrolysates of fish, jellyfish,
      chicken, porcine and bovine collagen. Supported by molecular modeling
      calculations, the AFM and NMR experiments provide a detailed knowledge about the
      composition of collagen hydrolysates and collagen ointments. Furthermore, the
      data allow a correlation between the size of the fragments and their potential
      bioactivity.

PMID- 22855354
TI  - Two-stage dose finding for cytostatic agents in phase I oncology trials.
AB  - Conventional dose-finding methods in oncology are mainly developed for cytotoxic
      agents with the aim of finding the maximum tolerated dose. In phase I clinical
      trials with cytostatic agents, such as targeted therapies, designs with toxicity
      endpoints alone may not work well. For cytostatic agents, the goal is often to
      find the most efficacious dose that is still tolerable, although these agents are
      typically less toxic than cytotoxic agents and their efficacy may not
      monotonically increase with the dose. To effectively differentiate doses for
      cytostatic agents, we develop a two-stage dose-finding procedure by first
      identifying the toxicity upper bound of the searching range through dose
      escalation and then determining the most efficacious dose through dose de
      escalation while toxicity is continuously monitored. In oncology, treatment
      efficacy often takes a relatively long period to exhibit compared with toxicity.
      To accommodate such delayed response, we model the time to the efficacy event by
      redistributing the mass of the censored observation to the right and compute the
      fractional contribution of the censored data. We evaluate the operating
      characteristics of the new dose-finding design for cytostatic agents and
      demonstrate its satisfactory performance through simulation studies.

PMID- 22855353
TI  - Pericardial syndromes: an update after the ESC guidelines 2004.
AB  - Despite a myriad of causes, pericardial diseases present in few clinical
      syndromes. Acute pericarditis should be differentiated from aortic dissection,
      myocardial infarction, pneumonia/pleuritis, pulmonary embolism, pneumothorax,
      costochondritis, gastroesophageal reflux/neoplasm, and herpes zoster. High-risk
      features indicating hospitalization are: fever >38  degrees C, subacute onset,
      large effusion/tamponade, failure of non-steroidal anti-inflammatory drugs
      (NSAIDs), previous immunosuppression, trauma, anticoagulation, neoplasm, and
      myopericarditis. Treatment comprises 10-14-days NSAID plus 3 months colchicine (2
      * 0.5 mg; 1 * 0.5 mg in patients <70 kg). Corticosteroids are avoided, except for
      autoimmunity, as they facilitate the recurrences. Echo-guided pericardiocentesis
      (+/-fluoroscopy) is indicated for tamponade and effusions >2 cm. Smaller
      effusions are drained if neoplastic, purulent or tuberculous etiology is
      suspected. In recurrent pericarditis, repeated testing for autoimmune and thyroid
      disease is appropriate. Pericardioscopy and pericardial/epicardial biopsy may
      clarify the etiology. Familial clustering was recently associated with tumor
      necrosis factor receptor-associated periodic syndrome (TNFRSF1A gene mutation).
      Treatment includes 10-14 days NSAIDs with colchicine 0.5 mg bid for up to 6
      months. In non-responders, low-dose steroids, intrapericardial steroids,
      azathioprine, and cyclophosphamide can be tried. Successful management with
      interleukin-1 receptor antagonist (anakinra) was recently reported.
      Pericardiectomy remains the last option in >2 years severely symptomatic
      patients. In constriction, expansion of the heart is impaired by the rigid,
      chronically inflamed/thickened pericardium (no thickening ~20 %). Chest
      radiography, echocardiography, computerized tomography, magnetic resonance
      imaging, hemodynamics, and endomyocardial biopsy indicate the diagnosis.
      Pericardiectomy is the only treatment for permanent constriction. Predictors of
      poor survival are prior radiation, renal dysfunction, high pulmonary artery
      pressures, poor left ventricular function, hyponatremia, age, and simultaneous
      HIV and tuberculous infection.

PMID- 22855355
TI  - Tissue concentrations, bioaccumulation, and biomagnification of synthetic musks
      in freshwater fish from Taihu Lake, China.
AB  - Synthetic musks are ubiquitous pollutants in aquatic environments. As hydrophobic
      chemicals, they can accumulate in terrestrial and aquatic organisms.
      Investigations into the bioaccumulation of these chemicals in aquatic ecosystem
      have, however, been limited, and previous results were inconsistent among species
      and ecosystem. Studies on this topic have been carried out in European countries,
      the USA, and Japan, but very few are known of the situation in China. The aim of
      this study was to investigate contaminant levels of musks in fish from Taihu
      Lake, the second largest freshwater lake in China, as well as bioaccumulation and
      biomagnification of the pollutants in the freshwater food chain. Five polycyclic
      musks and two nitro musks were determined in 24 fish species and nine surface
      sediment samples from Taihu Lake. HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta[gamma]-2-benzopyran) and AHTN (7-acetyl-1,1,3,4,4,6
      hexamethyl-1,2,3,4-tetrahydronaphthalene) were the predominant contaminants in
      the fish samples, with concentrations ranging from below the limit of detection
      (LOD) to 52.9 and from <LOD to 7.5 ng/g lipid weight, respectively. Other
      contaminants were at low detection frequencies. The results indicated low
      concentrations of musks yet widespread occurrence of these contaminants in fish
      from Taihu Lake. Species-specific and lipid-related bioaccumulation
      characteristics were suggested, but no significant region-specific differences
      were observed. Normalized biota-sediment accumulation factors for HHCB and AHTN
      were noted to increase with trophic levels in fish. Trophic magnification factors
      were estimated at 1.12 for HHCB and 0.74 for AHTN. A biomagnification for HHCB,
      and probably biodilution for AHTN, in the freshwater food chain are indicated,
      when trophic magnification factors were concerned. However, the correlations
      between logarithmic concentrations of the chemicals and trophic levels were not
      statistically significant. Further study using long food chains in this lake is
      still needed.

PMID- 22855356
TI  - Biodegradation potential of ofloxacin and its resulting transformation products
      during photolytic and photocatalytic treatment.
AB  - The release of pharmaceuticals in the environment, as parent compounds,
      metabolites and transformation products, and the consequent risks posed to living
      organisms due to the unintended exposure of the latter to these chemicals are
      nowadays of increasing scientific concern. The development of advanced oxidation
      processes able to degrade these substances is in the core of the current research
      objectives, the main target being the removal of these compounds from
      wastewaters. Often the focus is on the removal of the parent compound only.
      However, these processes can form transformation products. Knowledge on the risk
      related to such transformation products is scarce. Among others, knowledge on
      their toxic effects and their biodegradability is of importance not only when
      they are present in the environment but also for the assessment of the advanced
      oxidation processes' efficiency applied for their degradation. Photolytic (UV
      irradiation) and photocatalytic treatment (UV irradiation in the presence of
      TiO(2)) of the fluoroquinolone ofloxacin were applied, and the biodegradability
      of the formed products was investigated using the Closed Bottle test (OECD 301
      D). Various transformation products, formed both during the photo(cata)lytic
      treatment and the Closed Bottle test, were identified using chromatographic
      analysis with an ultra high-performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) system. The transformation products formed during the
      phototreatments were found to be non-readily biodegradable as the biodegradation
      percentages were close to zero. The persistence of the various photo(cata)lytic
      transformation products during the Closed Bottle test may be attributed to the
      fluorine present in all the transformation products formed. The transformation
      products identified suggest that two transformation routes were present:
      decarboxylation and opening of the piperazinyl ring. Interestingly, it was
      observed that in the presence of a readily biodegradable carbon source (sodium
      acetate), the biodegradation percentage increased drastically for some of the
      photolytically treated samples. This was not the case for the photocatalytically
      treated samples, in which also mineralization of the parent compound was achieved
      faster. Further research is needed, however, in order to increase the
      understanding of the conditions that may lead to less potent and persistent
      substances during the application of such engineered or natural processes.

PMID- 22855357
TI  - Source apportionment of polycyclic aromatic hydrocarbons in surface sediments of
      the Bohai Sea, China.
AB  - A total of 112 surface sediment samples covering virtually the entire Bohai Sea
      were analyzed for polycyclic aromatic hydrocarbons (PAHs), in order to provide
      the extensive information of recent occurrence levels, distribution, possible
      sources, and potential biological risk of these compounds in this area. Surface
      sediment samples were collected from the Bohai Sea using a stainless steel grab
      sampler. Sixteen PAHs were determined by a Finnigan TRACE DSQ gas
      chromatography/mass spectrometry. Diagnostic ratios, cluster analysis, and
      principal component analysis (PCA) with multivariate linear regression (MLR) were
      performed to identify and quantitatively apportion the major sources of
      sedimentary PAHs in the Bohai Sea. Concentrations of total PAHs in the Bohai Sea
      ranged widely from 97.2 to 300.7 ng/g (mean, 175.7 +/- 37.3 ng/g). High
      concentrations of PAHs were found in the vicinity of Luan River Estuary
      Qinhuangdao Harbor, Cao River Estuary-Bohai Sea Center, and north of the Yellow
      River Estuary. The three-ring PAHs were most abundant, accounting for about 37 +/
      5 % of total PAHs. The four-ring and five-ring PAHs were the next dominant ones
      comprising approximately 29 +/- 7 and 23 +/- 3 % of total PAHs, respectively.
      Concentrations of acenaphthylene, acenaphthene, and dibenz[a,h]anthracene are
      higher than Canadian interim marine sediment quality guideline values at most of
      the sites in the study area. Contamination levels of PAHs in the Bohai Sea were
      low in comparison with other coastal sediments in China and developed countries.
      The distribution pattern of PAHs and source identification implied that PAH
      contamination in the Bohai Sea mainly originates from petrogenic and pyrogenic
      sources. Further PCA/MLR analysis suggested that the contributions of spilled oil
      products (petrogenic), coal combustion, and traffic-related pollution were 39,
      38, and 23 %, respectively. Pyrogenic sources (coal combustion and traffic
      related pollution) contributed 61 % of anthropogenic PAHs to sediments, which
      indicates that energy consumption could be a dominant factor in PAH pollution in
      this area. Acenaphthylene, acenaphthene, and dibenz[a,h]anthracene are the three
      main species of PAHs with more ecotoxicological concern in the Bohai Sea.

PMID- 22855358
TI  - Differentiation and characterization of dendritic cells from human embryonic stem
      cells.
AB  - Human embryonic stem cells (hESCs) offer great hope in regenerative medicine.
      Their ability to give rise to almost any type of cell present in the adult body
      makes them an invaluable tool in finding cures for a variety of diseases. While
      considerable protocols have been devised to efficiently differentiate hESCs into
      various cells types including cells of hematopoietic origin, this protocol will
      focus on the derivation of dendritic cells (DC), a potent antigen-presenting
      cell. DCs are a highly important arm of the immune system, as they represent one
      of the few cells that bridge the innate and adaptive systems, leading to
      effective pathogen clearance. The study of DCs has led to potential applications
      in diverse fields, such as vaccine development, tumor immunology, and
      transplantation. In this protocol, we describe two different methods of
      differentiating hESCs into DCs. The first method uses OP9 bone marrow stromal
      supporting cells as a coculture system, while the second method utilizes the
      formation of embryoid body (EB, cellular aggregate) as an approach. To assure the
      successful outcome and subsequent assessment of the differentiated DCs,
      supporting protocols have been included in this chapter.

PMID- 22855359
TI  - Generation and characterization of mouse basophils from bone marrow and
      purification of basophils from spleen.
AB  - Basophils are rare circulating granulocytes that originate from progenitor cells
      in the bone marrow and have been considered important effector cells in IgE
      mediated allergic inflammation. Basophils constitute <1% of blood leukocytes and
      are usually absent or present only in small numbers in tissues. They may,
      however, be recruited to inflammatory sites when an antigen is present and
      contribute immediately to hypersensitivity reactions. Basophils can therefore
      serve as primary effector cells in allergic disorders. Despite a large pool of
      experimental evidence that has led to the discovery of these functional
      attributes of basophils, many questions regarding their contribution to these
      immune responses remain unanswered. This is due, in part, to the lack of methods
      for generation and purification of basophils and the lack of animal models
      appropriate for their functional analysis. Recent studies, however, have revealed
      a role for basophils as antigen-presenting cells that preferentially induce Th2
      cells in response to complexes of antigen plus antigen-specific IgE, to protease
      allergens, or to helminth parasites in vitro and in vivo through the production
      of "early IL-4" and the presentation to CD4(+) T cells of complexes of peptide
      plus MHC class II molecules. These findings have uncovered previously unknown
      functional characteristics of basophils. Knowledge of these and other functional
      properties of basophils may translate into the design of novel therapeutic
      strategies for Th2-IgE-mediated diseases, such as bronchial asthma. In this unit,
      protocols that will enable the study of mouse basophils are described.

PMID- 22855360
TI  - Isolation of human eosinophils.
AB  - Highly purified eosinophils can be isolated from peripheral blood by negative
      selection using an antibody-based magnetic negative selection protocol. The basic
      protocol describes a sequential fractionation of peripheral blood in which CD16+
      granulocytes are enriched first from whole blood, followed by isolation of
      eosinophils. This technique is easy to use, fast, and highly reproducible.
      Support protocols describe a staining methods that can be used to evaluate the
      purity of eosinophils and differentiation from other leukocyte populations.

PMID- 22855361
TI  - New strategy in hepatic metastatic colorectal cancer: tomotherapy and
      capecitabine followed by hepatic surgical resection.
AB  - The majority of patients who develop liver metastases in metastatic colorectal
      cancer (mCRC) has often unresectable disease. Several new methods of nonsurgical
      ablation have been tested with variable success. Helical tomotherapy (HT), such
      as intensity-modulated radiation therapy (IMRT) or stereotactic body radiotherapy
      therapy, is a recent radiation therapy technique which can provide simultaneous
      and precise targeting of multiple lesions, while sparing normal tissues. We
      retrospectively assess the feasibility and the tolerance of IMRT with
      capecitabine followed by hepatic surgery in mCRC patients. This original
      observation suggests that HT could be safely integrated in the multidisciplinary
      management of patients with metastatic colorectal cancer as an alternative to
      surgery or other local ablation therapies.

PMID- 22855362
TI  - Overexpression of miR-221 is associated with aggressive clinicopathologic
      characteristics and the BRAF mutation in papillary thyroid carcinomas.
AB  - Correlation between clinicopathogenetic features and the expression of specific
      miRNAs is unclear in papillary thyroid carcinoma (PTC). We therefore sought to
      assess whether miR-221 was associated with aggressive clinicopathologic
      characteristics and the BRAF mutation. We studied the expression levels of miR
      221 using northern blot quantitated by scion image in 51 cases of PTCs. The
      status of BRAF of PTCs was analyzed through direct DNA sequencing. Mann-Whitney U
      test was used to analyze different expression of miR-221 in PTCs with distinct
      clinicopathogenetic characteristics including gender, age, tumor size,
      multifocality, extrathyroidal invasion, disease stages, node metastasis, and BRAF
      status. Compared with the normal thyroid tissues, the relative expression of miR
      221 in tumor tissues was significantly upregulated (p < 0.001). Overexpression of
      miR-221 was significantly associated with extrathyroidal invasion (p = 0.001),
      lymph node metastasis (p = 0.046), advanced disease stages III-IV (p = 0.001),
      and the BRAF mutation (p = 0.014). While among BRAF wild tumors, miR-221 was only
      associated with extarthyroidal invasion, it showed strong association with all
      above aggressive features among BRAF mutation tumors. MiR-221 may be of potential
      importance in determining the aggressive properties of PTCs including the BRAF
      mutation, and it may further refine the risk stratification by BRAF mutation in
      PTCs.

PMID- 22855363
TI  - A comparative study between clinical grading of anterior chamber flare and flare
      reading using the Kowa laser flare meter.
AB  - To assess the accuracy of standard clinical grading of aqueous flare in uveitis
      according to the Standardization of Uveitis Nomenclature consensus, and compare
      the results with the readings of the laser flare meter, Kowa 500. Two examiners
      clinically graded the flare in 110 eyes. The flare was then measured using the
      Kowa laser flare meter. Twenty-nine eyes were graded as anterior chamber flare
      +2; for 18 of these, the clinicians were in agreement, the rest differed by the
      order of one grade. The range of the laser flare meter for these eyes was 5.2
      899.1 photons/ms. The median value was 41.4. Seventy-four eyes were graded with
      flare +1. Agreement was established in 51 of these eyes. Disagreement for the
      rest was again by the order of 1, and the flare meter range was 1.1-169.9
      photons/ms, median value 18.4. For the clinical measure of flare 0, the
      clinicians disagreed on three out of five eyes. The flare meter readings ranged
      from 2.5 to 14.1 photons/ms, median value 9.9. Only two eyes were graded with
      flare +3 and there was one step disagreement on both of them. We found little
      evidence of association between the flare readings and intraocular pressure or
      age. Our findings suggest that clinical evaluation of aqueous flare is
      subjective. Compared with the Kowa laser flare meter's numeric readings, the
      discrepancies observed indicate that clinical grading is an approximate science.
      The laser flare meter provides an accurate, reproducible, non-invasive assessment
      of aqueous flare that can prove valuable in research and clinical decisions. 

PMID- 22855364
TI  - Self-assembled monolayers with dynamicity stemming from (bio)chemical
      conversions: from construction to application.
AB  - Surfaces with "dynamicity" whereby surface properties can be modulated by an
      external stimulus on user demand have been actively exploited for the past
      decade. These switchable surfaces with dynamic properties are widely used for a
      number of applications such as micro/nanoarrays, biomolecule immobilization,
      basic cell studies, and tissue engineering on a variety of materials. This
      minireview highlights the dynamic control of surface properties on self-assembled
      monolayers and focuses on dynamicity that stems from (bio)chemical conversions
      achieved by electrical potentials, photoillumination, chemical reagents, enzymes,
      and pH.

PMID- 22855365
TI  - Identification, molecular characterisation and antimicrobial susceptibility of
      genomovars of the Burkholderia cepacia complex in Spain.
AB  - Burkholderia spp. strains collected in Spain over a 13-year period from patients
      with cystic fibrosis (CF) (n = 148), non-CF patients (n = 103) and from
      environmental sources (n = 64) were characterised. One hundred and forty-one of
      the examined strains were involved in seven suspected nosocomial disease
      outbreaks. Strains were identified by their 16s rRNA and recA genes. Their
      genetic relatedness, the possession of cable pili and the B. cepacia epidemic
      strain marker (BCESM), and their susceptibility to antimicrobial agents were
      studied using pulsed-field gel electrophoresis (PFGE), cblA and esmR genes
      analysis, and by the E-test, respectively. The genomovar distribution for the 315
      strains was as follows: B. stabilis 29.5 %, B. cepacia 14.9 %, B. multivorans
      11.1 %, B. cenocepacia IIIA 9.5 %, B. vietnamiensis 3.8 %, B. cenocepacia IIIB
      3.5 %, and B. ambifaria and B. pyrrocinia 0.3 % each. The genetic diversity of
      the B. cepacia complex (Bcc) was ample, with 57 different SpeI types, showing a
      genetic similarity of 36.4-96.6 %. No strain carried cblA, whereas 25 B.
      cenocepacia genotypes harboured BCESM (23 from patients with CF). Antimicrobial
      resistance rates to tobramycin (TOB; 86 %) and imipenem (IPM; 67 %) were high.
      The strains from patients with CF showed significantly greater resistance to
      piperacillin (PIP), levofloxacin (LVX) and co-trimoxazole (SXT) than those
      isolated from non-CF patients (p < 0.05). In conclusion, B. cenocepacia was the
      most prevalent genomovar found in patients with CF (19.1 %), whereas B. cepacia
      was the most common among non-CF patients (20.7 %). B. stabilis (47.6 %) was the
      most common environmental genomovar. Susceptibility to antimicrobial agents
      depended on genomovar status and strain origin.

PMID- 22855366
TI  - Periodontal infections and community-acquired pneumonia: a case-control study.
AB  - The aim of this study was to evaluate if the presence of periodontal infections
      (PI) is associated with community-acquired pneumonia (CAP) in a group of patients
      admitted to a hospital. A total of 140 patients were enrolled in this case
      control study, with 70 patients having CAP (case group) and the other 70 patients
      diagnosed with other systemic diseases (control group). A periodontal examination
      was carried out to assess pocket probing depth (PPD), clinical attachment loss
      (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and
      BOP showed higher scores in the case group over the control group. They were,
      respectively, 3.16 +/- 2.43 mm and 0.33 +/- 0.24 % for the case group, and 1.99
      +/- 2.23 mm and 0.25 +/- 0.24 % for the control group (p < 0.05). High scores for
      BP were observed in both groups (case: 97.1 %; control: 98.6 %, p = 1.0000).
      Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %;
      control: 41.4 %). The presence of moderate or severe CP increased the risk for
      CAP [odds ratio (OR) = 4.4, 95 % confidence interval (CI) = 1.4-13.8], even when
      adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic
      periodontitis were associated with CAP in this study.

PMID- 22855368
TI  - Statistical considerations when using a composite endpoint for comparing
      treatment groups.
AB  - When comparing two treatment groups in a time-to-event analysis, it is common to
      use a composite event consisting of two or more distinct outcomes. The goal of
      this paper is to develop a statistical methodology to derive efficiency
      guidelines for deciding whether to expand a study primary endpoint from E1 (for
      example, non-fatal myocardial infarction and cardiovascular death) to the
      composite of E1 and E2 (for example, non-fatal myocardial infarction,
      cardiovascular death or revascularisation). We investigate this problem by
      considering the asymptotic relative efficiency of a log-rank test for comparing
      treatment groups with respect to a primary relevant endpoint E1 versus the
      composite primary endpoint, say E, of E1 and E2, where E2 is some additional
      endpoint.

PMID- 22855369
TI  - Hydrogen activation by an intramolecular boron Lewis acid/zirconocene pair.

PMID- 22855367
TI  - ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise
      related phenotypes in older women in response to a muscle power training stimuli.
AB  - Genetic variation of the human ACE I/D and ACTN3 R577X polymorphisms subsequent
      to 12 weeks of high-speed power training on maximal strength (1RM) of the arm and
      leg muscles, muscle power performance (counter-movement jump), and functional
      capacity (sit-to-stand test) was examined in older Caucasian women [n = 139; mean
      age 65.5 (8.2) years; 67.0 (10.0) kg and 1.57 (0.06) m]. Chelex 100 was used for
      DNA extraction, and genotype was determined by PCR-RFLP methods. Muscular
      strength, power, and functional testing were conducted at baseline (T1) and after
      12 weeks (T2) of high-speed power training. At baseline, the ACE I/D and ACTN3
      R/X polymorphisms were not associated with muscle function or muscularity
      phenotypes in older Caucasian women. After the 12-week high-speed training
      program, subjects significantly increased their muscular and functional capacity
      performance (p < 0.05). For both polymorphisms, significant genotype-training
      interaction (p < 0.05) was found in all muscular performance indices, except for
      1RM leg extension in the ACE I/D (p = 0.187). Analyses of the combined effects
      between genotypes showed significant differences in all parameters (p < 0.05) in
      response to high-speed power training between the power (ACTN3 RR + RX & ACE DD)
      versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Our
      data suggest that the ACE and ACTN3 genotypes (single or combined) exert a
      significant influence in the muscle phenotypes of older Caucasian women in
      response to high-speed power training. Thus, the ACE I/D and ACTN3 R/X
      polymorphisms are likely factors in modulating exercise-related phenotypes in
      older women, particularly in response to a resistance training stimuli.

PMID- 22855370
TI  - Surface-charge-dependent nanoparticles accumulation in inflamed skin.
AB  - Polymeric nanoparticles (NPs) are interesting drug carriers for dermal
      application and drug targeting to certain skin structures. NP interactions with
      diseased skin and the associated benefits and risks have been hardly explored.
      Today, we study the behavior of polymeric NPs for selective drug delivery to
      inflamed skin. Neutral, cationic, and anionic NPs of nominal diameters around 100
      nm were administered to an experimental dithranol-induced dermatitis inflammation
      model in mice ears. The results showed that the surface charge had an important
      influence on the penetration and accumulation tendency in the inflamed skin
      compared with the neutral and cationic (2.8 +/- 0.3%, 2.1 +/- 0.2%, and 1.9 +/-
      0.3% for anionic, neutral, and cationic particles, respectively). Confocal laser
      scanning microscopy showed that all particles were accumulated in the inflamed
      pilosebaceous units. Betamethasone-loaded NPs showed that both charged particles
      were therapeutically more efficient than the neutral ones. Treatment with anionic
      and cationic particles led to the reduction of the inflammatory enzyme alkaline
      phosphatase activity by 50.7 +/- 2% and 57.7 +/- 5%, respectively, in comparison
      with the inflamed control. Noncharged particles had a lower therapeutic impact
      where the activity was only reduced by a factor of 75%. Histological sections
      examination had also confirmed these results. Therefore, it was concluded that
      the presence of charge could enhance skin-NPs adhesion and interaction leading to
      higher therapeutic effect on inflamed skin.

PMID- 22855371
TI  - 'Further Development' of Mendel's legacy? Erich von Tschermak-Seysenegg in the
      context of Mendelian-biometry controversy, 1901-1906.
AB  - The contribution of Erich von Tschermak-Seysenegg (1871-1962) to the beginning of
      classical genetics is a matter of dispute. The aim of this study is to analyse,
      based on newly accessible archive materials, the relevance of his positions and
      theoretical views in a debate between advocates of early Mendelian explanation of
      heredity and proponents of biometry, which took place in England around 1901
      1906. We challenge not only his role of an 'external consultant', which at the
      time de facto confirmed his status of 'rediscoverer' of Mendel's work but also
      analyse his ambivalent positions which are to be seen as a part of 'further
      development' (Weiterfuhrung), a development of Mendel's legacy as he understood
      it. Second, there is an interesting aspect of establishing connections within an
      'experimental culture' along the Mendel's lines of thought that was parallel to
      the first step of institutionalizing the new discipline of Genetics after
      1905/06. Part of the study is also the analysis of contribution of his older
      brother Armin von Tschermak-Seysenegg (1870-1952) who--much like in the case of
      'rediscovery' of 1900-1901--was for his younger brother an important source of
      theoretical knowledge. In this particular case, it regarded Bateson's 'Defence'
      of Mendel from 1902.

PMID- 22855372
TI  - Prevalence and onset of regression within autism spectrum disorders: a meta
      analytic review.
AB  - Rates and onset of regression were meta-analyzed from 85 articles representing
      29,035 participants with autism spectrum disorders (ASD). Overall prevalence rate
      for regression was 32.1, 95 % CI [29.5, 34.8] occurring at mean of 1.78 years, 95
      % CI [1.67, 1.89]. Regression prevalence rates differed according to four types
      of regression: language regression, 24.9 %; language/social regression, 38.1 %;
      mixed regression, 32.5 %; and unspecified regression, 39.1 %. Regression
      prevalence also differed according to sampling method: population-based
      prevalence was 21.8 %, clinic-based prevalence was 33.6 %, and parent survey
      based prevalence was 40.8 %. Risk of regression was equal for males and females,
      but higher for individuals diagnosed with autism versus another ASD. Later age of
      regression onset was predicted by older age of child.

PMID- 22855373
TI  - Chlamydiaceae family, Parachlamydia spp., and Waddlia spp. in porcine abortion.
AB  - At present, despite extensive laboratory investigations, most cases of porcine
      abortion remain without an etiological diagnosis. Due to a lack of recent data on
      the abortigenic effect of order Chlamydiales, 286 fetuses and their placentae of
      113 abortion cases (1-5 fetuses per abortion case) were investigated by
      polymerase chain reaction (PCR) methods for family Chlamydiaceae and selected
      Chlamydia-like organisms such as Parachlamydia acanthamoebae and Waddlia
      chondrophila. In 0.35% of the cases (1/286 fetuses), the Chlamydiaceae real-time
      PCR was positive. In the Chlamydiaceae-positive fetus, Chlamydia abortus was
      detected by a commercial microarray and 16S ribosomal RNA PCR followed by
      sequencing. The positive fetus had a Porcine circovirus-2 coinfection. By the
      Parachlamydia real-time PCR, 3.5% (10/286 fetuses of 9 abortion cases) were
      questionable positive (threshold cycle values: 35.0-45.0). In 2 of these 10
      cases, a confirmation by Chlamydiales-specific real-time PCR was possible. All
      samples tested negative by the Waddlia real-time PCR. It seems unlikely that
      Chlamydiaceae, Parachlamydia, and Waddlia play an important role as abortigenic
      agents in Swiss sows.

PMID- 22855374
TI  - Limited yield of diagnoses of intrahepatic infectious causes of canine
      granulomatous hepatitis from archival liver tissue.
AB  - Canine granulomatous hepatitis is an uncommon morphologic diagnosis that has been
      associated with a variety of diseases, including a number of systemic infectious
      etiologies. Formalin-fixed, paraffin-embedded (FFPE) tissues are typically the
      only source of liver tissue remaining for additional testing for the presence of
      infectious disease within granulomas. It is unclear if the more common infectious
      culprits of granulomatous hepatitis can be identified from such specimens. The
      aim of the current study was to retrospectively investigate archival FFPE liver
      tissue from dogs with granulomatous hepatitis for the presence of infectious
      agents. Semiquantitative analysis of copper accumulation in liver specimens was
      also performed. Medical records were examined for recorded evidence of systemic
      infectious disease diagnosis. Formalin-fixed, paraffin-embedded liver was
      prospectively evaluated for infectious agents via differential staining
      techniques (n = 13), eubacterial fluorescent in situ hybridization (n = 11), and
      Bartonella polymerase chain reaction assays (n = 15). An infectious cause of
      granulomatous hepatitis was not identified within liver tissue from any dog using
      these diagnostic methodologies. Six out of 25 (24%) dogs were diagnosed with
      concurrent systemic or localized bacterial infections at the time of
      presentation. Nine out of 17 (53%) dogs had excessive hepatic copper accumulation
      when evaluated by a semiquantitative histologic grading scheme or quantitative
      copper analysis. As definitive infectious causes of granulomatous hepatitis were
      not identified within archival liver biopsy samples, it was concluded that
      investigation of infectious etiologies within FFPE liver specimens using these
      diagnostic approaches may be of low yield.

PMID- 22855375
TI  - A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus.
AB  - Rapid, sensitive, and automatic detection platforms are among the major
      approaches of controlling viral diseases in aquaculture. An efficient detection
      platform permits the monitoring of pathogen spread and helps to enhance the
      economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the
      cause of viral encephalopathy and retinopathy, is among the most devastating
      aquaculture viruses that infect marine fish species worldwide. In the present
      study, a highly sensitive magnetoreduction assay was developed for detecting
      target biomolecules with a primary focus on NNV antigens. A standard curve of the
      different NNV concentrations that were isolated from infected Malabar grouper
      (Epinephelus malabaricus) was established before experiments were conducted. The
      test solution was prepared by homogeneous dispersion of magnetic nanoparticles
      coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution
      were oscillated by magnetic interaction with multiple externally applied,
      alternating current magnetic fields. The assay's limit of detection was
      approximately 2 * 10(1) TCID(50)/ml for NNV. Moreover, the immunomagnetic
      reduction readings for other aquatic viruses (i.e., 1 * 10(7) TCID(50)/ml for
      Infectious pancreatic necrosis virus and 1 * 10(6.5) TCID(50)/ml for grouper
      iridovirus) were below the background noise in the NNV solution, demonstrating
      the specificity of the new detection platform.

PMID- 22855376
TI  - Occurrence of antimicrobial resistance and virulence genes, and distribution of
      enterococcal clonal complex 17 from animals and human beings in Korea.
AB  - Enterococci are major zoonotic bacteria that cause opportunistic infections in
      human beings and animals. Moreover, pathogenic strains can be disseminated
      between human beings and animals, particularly companion animals that come into
      frequent contact with people. Recently, Enterococcus faecium clonal complex 17
      (CC17) has emerged as a pandemic clone. Most CC17 strains are ampicillin
      resistant and possess virulence genes such as esp and hyl. Despite the possible
      dissemination of CC17 between human beings and animals, prevalence data about
      CC17 in animals is limited. In the present study, the phenotypes and genotypes of
      antimicrobial resistance were compared, as well as virulence gene profiles from
      184 enterococci strains isolated from chickens, pigs, companion animals, and
      human patients in Korea. Ampicillin-resistant E. faecium (AREF) strains were
      selected, and multilocus sequence typing was performed to investigate the
      dispersion of CC17 among animals and human beings. The companion animal and human
      isolates showed high resistance rates to ampicillin and ciprofloxacin, whereas
      food animal isolates showed high tetracycline and erythromycin resistance rates.
      Ampicillin-resistant E. faecium was only detected in human (21/21 E. faecium,
      100%) and companion animal (3/5 E. faecium, 60%) isolates, and all human AREF
      strains and 1 canine AREF strain were confirmed as CC17. In conclusion, the
      occurrence of antimicrobial resistance and virulence genes, and the distribution
      of enterococcal CC17 in companion animal enterococcal strains were similar to
      those of human strains rather than to those of food animal strains.

PMID- 22855377
TI  - Development of an antigen-capture enzyme-linked immunosorbent assay for
      Clostridium perfringens beta2-toxin in porcine feces and the neonatal piglet
      intestine.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for detection and
      quantitation of beta2-toxin in neonatal piglet intestinal contents. Polystyrene
      plates were coated with polyclonal capture antibodies prepared against consensus
      recombinant beta2-toxin. The ELISA was developed using consensus recombinant
      beta2-toxin, atypical recombinant beta2-toxin, purified consensus native beta2
      toxin, and field samples of neonatal porcine intestinal contents. Captured
      antigen was detected using a horseradish peroxidase-labeled monoclonal antibody
      against consensus recombinant beta2-toxin. The limit of detection of the ELISA
      for consensus beta2-toxin was between 2.0 and 3.5 ng/ml. The ELISA detected
      atypical recombinant beta2-toxin only weakly. Optical density was protein
      concentration dependent. The test confirmed differences between consensus and
      atypical recombinant beta2-toxin, but similar results obtained when testing pure
      consensus recombinant beta2-toxin and native beta2-toxin. Results obtained from
      intestinal content samples, particularly from the small intestine, were highly
      inconsistent and suggested variable protease activity. Addition of protease
      inhibitors partially prevented degradation of the toxin; however, sample
      processing at low temperature, at a lower pH (citrate buffer with 5% of bovine
      serum albumin, pH 6.1), and "cold incubation" of applied antigens abolished
      protease activity. The recombinant toxin was preserved in spiked intestinal
      samples by freezing at -70 degrees C, suggesting that necropsy samples can be
      stored frozen for periodic testing. With appropriate sample preparation, antigen
      capture ELISA can detect beta2-toxin in the intestinal content and feces of
      neonatal piglets.

PMID- 22855378
TI  - Performance analysis of rapid diagnostic tests on atypical bovine spongiform
      encephalopathy.
AB  - The preferred method to determine the prevalence of bovine spongiform
      encephalopathy (BSE) in a country is to use immunology-based rapid-tests. Though
      these tests are validated to detect C-type BSE disease-associated prion
      (PrP(sc)), test-specific properties may influence their ability to detect H-
      and/or L-type BSE PrP(sc), where both are atypical from C-type PrP(sc). Molecular
      characterization shows atypical BSE PrP(sc) to have a different sensitivity to
      proteinase activity and different affinities for certain prion-specific
      antibodies. It is important to understand how atypical BSE PrP(sc) may affect the
      performance of rapid-tests, which are typically dependent on the use of specific
      proteases and antibodies. The current study used experimentally generated C-, H-,
      and L-type BSE PrP(sc) to evaluate 3 tests used in various national BSE
      surveillance programs: an immunochromatographic assay, a standard sandwich enzyme
      linked immunosorbent assay (stndELISA), and a PrP(sc)-conformation-specific ELISA
      (confELISA). Although BSE PrP(sc) type had some effects on rapid-test
      performance, analytical sensitivity for atypical BSE PrP(sc) on all 3 platforms
      was not significantly compromised. When testing for atypical BSE PrP(sc), the 3
      tests were able to meet the same requirements that the European Food Safety
      Authority set when evaluating the tests for C-type BSE PrP(sc).

PMID- 22855379
TI  - Cerebrospinal nematodiasis outbreak in an urban outdoor aviary of cockatiels
      (Nymphicus hollandicus) in southern California.
AB  - An outbreak of cerebrospinal nematodiasis due to Baylisascaris sp. was documented
      in an urban outdoor aviary in southern California. Thirty-four out of 35
      cockatiels (Nymphicus hollandicus, 97%) showed a variety of neurological signs
      including ataxia, lateral recumbency, opisthotonus, and torticollis. Thirteen
      carcasses were submitted for necropsy; the histological lesions were restricted
      to the central nervous system (brain and spinal cord) and were predominantly
      degenerative, characterized by multifocal white matter vacuolation, gliosis,
      axonal swelling, gitter cell infiltration, and mild hemorrhage, rarely
      accompanied by mild granulomatous inflammation and mild lymphocytic perivascular
      cuffs. Nematode larvae morphologically compatible with Baylisascaris sp. were
      observed in the brain of 5 birds, away from the lesion site.

PMID- 22855380
TI  - The "Swiss-cheese Doppler-guided laser tonsillectomy": a new safe cribriform
      approach to intracapsular tonsillectomy.
AB  - Outpatient laser ablation of palatine tonsils is a very interesting procedure
      that has been recently introduced as a routine in head and neck surgery
      departments. The aim of this study was to describe a new strategy using a Doppler
      guided fibre optic neodymium-yttrium-aluminium-garnet (YAG) laser to remove up to
      80 % of tonsillar tissue, as assessed in the long-term postoperative clinical
      evaluation of the volume of the tonsils at the follow-up, and leaving the capsule
      in place, thus avoiding any haemorrhagic complication and minimize pain. A total
      of 20 patients (men, n=13; women, n=7), aged between 6 and 63, were recruited for
      the procedure. They were affected by chronic hypertrophic tonsillitis with a
      recurrent fever and other symptoms that were related to oral inflammation. Among
      the 20 patients, no serious adverse events, including haemorrhage-related
      complications, were observed. Treatment was well tolerated, even in patients
      displaying an overall low pain threshold. No dropout or uncompleted procedure
      occurred in the present study. Minor complications included sore throat, moderate
      oedema, mild acute pharynx inflammation, slight peritonsillar exudate and local
      burning. The postoperative pain, measured by Scott-Huskisson visual analogue
      scale, was between 5 and 40 mm and was easily counteracted by means of external
      ice packages and nonsteroidal anti-inflammatory drugs, according to the
      individual patient's need. During the 12-36-month follow-up patients showed
      improved symptoms (n=7) and complete recovery (n=13). A relapse episode was
      observed in two patients. This study supports fibre optic laser neodymium-YAG
      tonsil surgery, named "cribriform intracapsular tonsillectomy" or "Swiss-cheese
      laser tonsillectomy", as an effective alternative to the traditional cold knife
      approach or electrosurgery. This approach could become the gold standard for
      tonsil surgery in the third millennium for safety reasons, acceptable cost
      benefit ratio, the precise targeting of the beam across the affected tissues and
      the short- and long-term recovery.

PMID- 22855381
TI  - Finite element analysis of cornea thermal damage due to pulse incidental far IR
      laser.
AB  - Due to the wide use of laser systems in human activities, an accidental event of
      laser exposure may occur where the most susceptible part to injury is the eye. A
      typical invisible pulsed, far IR, CO2 laser beam was used as an intrabeam
      accidentally struck an eye leading to raise its temperature to a limit where a
      pain sensation was started followed by aversion response with a delay of 0.25 s.
      At this time, the laser beam was assumed to terminate with respect to the cornea.
      The finite element method (FEM) was used successfully to predict, numerically,
      the temperature distribution through the anterior part of the eye when subjected
      to the laser beam. The FEM program was written using Visual Basic 6 coding. The
      effects of laser parameters such as laser beam profile, pulse width, and
      repetition rate on the temperature distribution and the consequential thermal
      damage were studied. The efficiency of the constructed computer program of the
      present work was examined by the comparison of the predicted results with those
      obtained from previously published experimental and theoretical works. The
      comparison shows good agreements.

PMID- 22855382
TI  - Shear strength of composite bonded to Er:YAG laser-prepared enamel: an in vitro
      comparative study.
AB  - The primary objective of this study is to investigate the adhesion properties
      between four current generations of bonding systems and enamel surface
      conditioned by Er:YAG laser, using an energy density comparable to the ablation
      threshold of enamel. By including an energy density comparable to published
      adhesion studies, the secondary objective is to compare the adhesion effects of
      these selected laser conditioning parameters on enamel with other similar
      published studies. MATERIAL AND METHODS: Buccal sides of randomly selected human
      molars (N=117) were prepared and divided into nine experimental groups depending
      on the generations of bonding system represented by the corresponding number (G4,
      G5, G6, G7) and the additional laser conditioning on the enamel surface
      represented by laser etch (LE) and laser etch with a higher pulse energy,
      followed by acid etch (AE), if required. The bonding resin systems and their
      specific requirements were applied after the enamel surfaces were laser
      conditioned following a specific set of laser parameters. Composite posts of 1.6
      mm in diameter and approximately 6 mm in length were then restored on each of the
      sample surfaces. After 48 h, the composite assemblies were tested to failure
      under compression using a knife edge loading head at a cross head speed of 1
      mm/min until the composite cylinders were separated from the surface. The data
      collected were then analyzed using one-way analysis of variance and SAS software
      program (9.1, TS1M3). RESULTS: No significant difference was found among these
      groups: AE+G4/LEAE+G4, G6/LE+G6, and G7/LE+G7. Significant differences were found
      in the remaining groups: AE+G5/LEAE+G5, AE+G5/LEAE-H+G5, and LEAE+G5/LEAE-H+G5.
      The bond strength results were compared among similar published data and possible
      influences from different laser parameters, bonding systems, and their combined
      impact on the enamel surface and its adhesion properties were analyzed.
      CONCLUSION: Under our specific settings, additional laser conditioning after
      phosphoric acid etch is beneficial to one generation of bonding resin (G5). There
      is no significant change or detrimental effect to the other three groups (G4, G6,
      and G7) of bonding resins with respect to their final bond strength. The
      published reports of lower bond strength after additional laser conditioning may
      be related to thermal damage or unfavorable alteration to the enamel surface by
      excessive laser energy and the chemistry of bonding systems studied. These
      factors will affect the overall wettability and the subsequent adhesion
      properties of the enamel surface.

PMID- 22855383
TI  - Prediction of the main route in the TiO2-photocatalyzed degradation of organic
      compounds in water by density functional calculations.
AB  - TiO(2) photocatalysis: It is shown theoretically that during photocatalysis by
      TiO(2) most organic molecules can be directly oxidized by trapped holes, while
      the oxidation of some organic molecules with low HOMO energies progresses mainly
      through indirect oxidation by .OH radicals.

PMID- 22855384
TI  - Quality of communication between primary health care and mental health care: an
      examination of referral and discharge letters.
AB  - In managing treatment for persons with mental illness, the primary care physician
      (PCP) needs to communicate with mental health (MH) professionals in various
      settings over time to provide appropriate management and continuity of care.
      However, effective communication between PCPs and MH specialists is often poor.
      The present study reviewed evidence on the quality of information transfer
      between PCPs and specialist MH providers for referral requests and after
      inpatient discharge. Twenty-three audit studies were identified that assessed the
      quality of content and nine that assessed strategies to improve quality. Results
      indicated that rates of item reporting were variable. Within the limited evidence
      on interventions to improve quality, use of structured forms showed positive
      results. Follow-up work can identify a minimum set of items to include in
      information transfers, along with item definitions and structures for holding
      this information. Then, methodologies for measuring data quality, including
      electronically generated performance metrics, can be developed.

PMID- 22855385
TI  - Gallstone abscess: some drops may end up costlier!

PMID- 22855386
TI  - Hydrogen peroxide induced activation of gene expression in mammalian cells using
      boronate estrone derivatives.
AB  - Keeping the boron out of the ER: A genetic switch was engineered that activates
      gene expression in the presence of H(2)O(2). The use of a boronate group on an
      estrone molecule allows for activation of gene expression through binding of the
      estrogen receptor only when the boron group is oxidized by H(2)O(2). This sensor
      is highly sensitive and specific for H(2)O(2).

PMID- 22855387
TI  - Thumb inhibitor binding eliminates functionally important dynamics in the
      hepatitis C virus RNA polymerase.
AB  - Hepatitis C virus (HCV) has infected almost 200 million people worldwide,
      typically causing chronic liver damage and severe complications such as liver
      failure. Currently, there are few approved treatments for viral infection. Thus,
      the HCV RNA-dependent RNA polymerase (gene product NS5B) has emerged as an
      important target for small molecule therapeutics. Potential therapeutic agents
      include allosteric inhibitors that bind distal to the enzyme active site. While
      their mechanism of action is not conclusively known, it has been suggested that
      certain inhibitors prevent a conformational change in NS5B that is crucial for
      RNA replication. To gain insight into the molecular origin of long-range
      allosteric inhibition of NS5B, we employed molecular dynamics simulations of the
      enzyme with and without an inhibitor bound to the thumb domain. These studies
      indicate that the presence of an inhibitor in the thumb domain alters both the
      structure and internal motions of NS5B. Principal components analysis identified
      motions that are severely attenuated by inhibitor binding. These motions may have
      functional relevance by facilitating interactions between NS5B and RNA template
      or nascent RNA duplex, with presence of the ligand leading to enzyme
      conformations with narrower and thus less accessible RNA binding channels. This
      study provides the first evidence for a mechanistic basis of allosteric
      inhibition in NS5B. Moreover, we present evidence that allosteric inhibition of
      NS5B results from intrinsic features of the enzyme free energy landscape,
      suggesting a common mechanism for the action of diverse allosteric ligands.

PMID- 22855388
TI  - Safety and immunogenicity of a meningococcal quadrivalent conjugate vaccine in
      five- to eight-year-old Saudi Arabian children previously vaccinated with two
      doses of a meningococcal quadrivalent polysaccharide vaccine.
AB  - Saudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent
      polysaccharide vaccine (MPSV4) when given before 2 years of age. This study
      examined whether such children were able to respond to 1 dose of quadrivalent
      meningococcal diphtheria toxoid conjugate vaccine (MCV4) when they were older.
      Saudi Arabian children 5 to 8 years of age who had previously been vaccinated
      with 2 doses of MPSV4 when they were under 2 years of age (termed the prior-MPSV4
      group) were enrolled in a controlled, open-label, multicenter study. In the prior
      MPSV4 group, children (n = 153) received 1 dose of MCV4, as did a group of age
      matched meningococcal vaccine-naive children (n = 85). Blood samples collected
      prevaccination and 28 days postvaccination were measured for serogroup-specific
      serum bactericidal antibody (SBA) levels in the presence of baby rabbit
      complement (rSBA) and for IgG antibody levels. Vaccine tolerability and safety
      were also evaluated. For all of the measured serogroups (A, C, Y, and W-135), the
      meningococcal vaccine-naive participants achieved higher postvaccination rSBA
      geometric mean titers (GMTs) than did those in the prior-MPSV4 group. This was
      statistically significant for serogroup C (512 versus 167). Percentages of
      participants with postvaccination titers of >=8 and with >=4-fold increases in
      prevaccination to postvaccination titers appeared to be quite similar in the 2
      groups. No worrisome safety signals were detected. MCV4 induced robust immune
      responses and was well tolerated in Saudi Arabian children who previously
      received 2 doses of MPSV4 as well as in those who were previously meningococcal
      vaccine naive.

PMID- 22855389
TI  - The absence of PspA or presence of antibody to PspA facilitates the complement
      dependent phagocytosis of pneumococci in vitro.
AB  - Pneumococcal surface protein A (PspA) is a surface molecule on pneumococci that
      is required for full virulence in mouse models of infection. PspA has been
      reported to inhibit complement deposition on the pneumococcal surface. It has
      been assumed that this decreased complement deposition results in the inefficient
      phagocytosis of wild-type pneumococci. However, an effect of PspA on phagocytosis
      had not been shown. Our present studies demonstrated that a loss of PspA by
      capsular type 3 strains WU2 and A66.1 led to enhanced complement-dependent
      phagocytosis of the pneumococci by the mouse macrophage cell line J774A.1. This
      observation was made using human complement as well as mouse complement. Since
      this enhanced phagocytosis could be blocked by antibody to complement receptor
      CR3 on J774A.1, it was concluded that PspA's effect on phagocytosis was due to
      its effect on the amount of deposited complement, which in turn helped opsonize
      the pneumococci for phagocytosis. Since these studies included new independent
      mutants lacking PspA, the results provide solid confirmation of the previously
      reported effects of PspA on pneumococcal virulence and complement deposition.
      Finally, we showed that antibody to PspA, which is also known to enhance
      complement deposition, also enhances the phagocytosis of pneumococci in a largely
      complement-dependent manner.

PMID- 22855390
TI  - Multiplex assay detection of immunoglobulin G antibodies that recognize Babesia
      microti antigens.
AB  - Human babesiosis, a blood-borne infection caused by several species of Babesia,
      including B. microti, is an emerging disease that is endemic in the Northeast,
      upper Midwest, and Pacific Northwest regions of the United States. Risk factors
      for babesiosis include exposure to the infected tick vector and blood
      transfusions from infected donors. In this work, we cloned and expressed two of
      the immunodominant antigens from B. microti and used them in a multiplex bead
      format assay (MBA) to detect parasite-specific IgG responses in human sera. The
      MBA using recombinant B. microti secreted antigen 1 (BmSA1) protein was more
      specific (100%) and slightly more sensitive (98.7%) than the assay using a
      truncated recombinant BMN1-17 construct (97.6% and 97.4%, respectively). Although
      some antibody reactivity was observed among sera from confirmed-malaria patients,
      only one Plasmodium falciparum sample was simultaneously positive for IgG
      antibodies to both antigens. Neither antigen reacted with sera from babesiosis
      patients who were infected with Babesia species other than B. microti. Both
      positive and negative MBA results were reproducible between assays and between
      instruments. Additional studies of these recombinant antigens and of the
      multiplex bead assay using blood samples from clinically defined babesiosis
      patients and from blood donors are needed to more clearly define their usefulness
      as a blood screening assay.

PMID- 22855391
TI  - The DBA/1 strain is a novel mouse model for experimental Borrelia burgdorferi
      infection.
AB  - Lyme arthritis, caused by Borrelia burgdorferi, has similarities to rheumatoid
      arthritis and its experimental murine model, collagen-induced arthritis (CIA).
      Currently, no common strain exists for examination of arthritis models of Lyme
      arthritis and CIA, which are typically studied in C3H/HeJ and DBA/1 mice,
      respectively. The aim of this study was to define the characteristics of Borrelia
      burgdorferi infection and arthritis in the DBA/1 murine strain. Murine Lyme
      arthritis was induced in C3H/HeJ and DBA/1 mice by subcutaneous infection with B.
      burgdorferi. Tibiotarsal joints were measured during infection, and mice were
      sacrificed for histologic, microbiologic, and serologic analysis on days 14 and
      42 postinfection. All bladder cultures obtained from C3H/HeJ and DBA/1 mice at 14
      days postinfection grew Borrelia. There was no significant difference in
      spirochetal burdens in hearts and tibiotarsal joints at days 14 and 42
      postinfection. Tibiotarsal joint swelling and histologic scoring were not
      significantly different between the two strains. Serologic analysis revealed
      increased IgG2a production in C3H/HeJ mice compared to DBA/1 mice. Analysis of 2
      dimensional immunoblots revealed several specific antigens (LA7, BBA03, BBA64,
      BBA73, OspA, and VlsE) which were not recognized by DBA/1 sera. We conclude that
      the DBA/1 murine strain is a suitable model for the study of Lyme arthritis and
      experimental B. burgdorferi infection, allowing direct comparison between Lyme
      arthritis and collagen-induced arthritis. The specificity of the humoral immune
      response differs between the two strains, further study of which may reveal
      important findings about how individual strains respond to B. burgdorferi
      infection.

PMID- 22855392
TI  - Dexamethasone downregulates the systemic cytokine response in patients with
      community-acquired pneumonia.
AB  - The influence of adjunctive corticosteroids on the cytokine response in community
      acquired pneumonia (CAP) is largely unknown. In this study, we analyzed the
      effect of dexamethasone on the cytokine response in patients with CAP and
      evaluated whether this effect is dependent on the causative microorganism. We
      hypothesized that dexamethasone has a larger effect on the cytokine response in
      patients with pneumococcal pneumonia than in patients with pneumonia caused by an
      atypical bacterium. A total of 304 hospitalized, nonimmunocompromised patients
      with CAP were randomized to an adjunctive 4-day course of 5 mg dexamethasone once
      a day (n = 151) or a placebo (n = 153). Serum concentrations of interleukin-1
      receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, IL-17, tumor necrosis factor
      alpha (TNF-alpha), gamma interferon (IFN-gamma), macrophage inflammatory protein
      1 alpha (MIP-1alpha), and monocyte chemotactic protein-1 (MCP-1) were measured on
      days 0, 1, 2, and 4 and at a control visit. Overall, the concentrations of IL-6
      (P < 0.01), IL-8 (P < 0.01), MCP-1 (P < 0.01), and TNF-alpha (P < 0.01) were
      significantly lower on day 2 in the dexamethasone group than in the placebo
      group. In patients with pneumococcal pneumonia (n = 72), both treatment groups
      showed a rapid decrease of cytokine concentrations; only the concentration of TNF
      alpha (P = 0.05) was significantly lower in the dexamethasone group on day 2. In
      patients with CAP caused by an atypical pathogen (Legionella pneumophila,
      Chlamydophila species, Coxiella burnetii, or Mycoplasma pneumoniae; n = 58), IL
      1Ra (P < 0.01), IL-6 (P < 0.01), and MCP-1 (P = 0.03) decreased more rapidly in
      the dexamethasone group than in the placebo group. In conclusion, dexamethasone
      downregulates the cytokine response during CAP. This effect seems to be dependent
      on the causative microorganism. This study provides insight into which patients
      with CAP might benefit most from adjunctive dexamethasone.

PMID- 22855393
TI  - Activation-induced FoxP3 expression regulates cytokine production in conventional
      T cells stimulated with autologous dendritic cells.
AB  - A defining feature of dendritic cells (DCs) is their ability to induce the
      proliferation of autologous T cells in the absence of foreign antigen-a process
      termed the "autologous mixed leukocyte reaction" (AMLR). We report that equine
      monocyte-derived DCs, but not macrophages, are potent inducers of the AMLR. The
      response is contact dependent and major histocompatibility complex class II
      dependent and primarily involves CD3(+) CD4(+) CD8(-) T cells. Upon stimulation
      with DCs or the mitogen concanavalin A, a subset of the proliferating T cells
      expresses the regulatory T-cell (Treg) transcription factor FoxP3. Although many
      of these FoxP3(+) T cells are capable of producing the effector cytokines
      interleukin-4 (IL-4) and gamma interferon (IFN-gamma), they are more likely to
      produce IL-10 and less likely to produce IFN-gamma than equivalent FoxP3(-)
      cells. Therefore, FoxP3 expression is an inherent component of equine T cell
      activation and is associated with a more immunosuppressive cytokine profile.
      These results confirm that FoxP3 expression in the horse, in contrast to the
      mouse, is regulated similarly to FOXP3 expression in humans and provide evidence
      that FoxP3 expression by conventional T cells may help regulate the developing
      immune response.

PMID- 22855394
TI  - Immunogenicity of a monovalent pandemic influenza A H1N1 virus vaccine with or
      without prior seasonal influenza vaccine administration.
AB  - The immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be
      modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We
      conducted a retrospective analysis of immunogenicity of 243 health care workers
      (number of sTIV-positive [sTIV(+)] subjects, 216; number of sTIV(-) subjects, 27)
      by hemagglutination inhibition. There was no significant difference in the ratios
      of antibody titers of >=40 (41.2% versus 48.1%; P = 0.49) and fold increases in
      geometric mean titer (3.8 versus 4.5; P = 0.37). sTIV injected 7 to 10 days prior
      to A/H1pdm vaccine administration did not interfere with the immunogenicity of
      the latter.

PMID- 22855395
TI  - Antibody in middle ear fluid of children originates predominantly from sera and
      nasopharyngeal secretions.
AB  - The human middle ear is devoid of any immunocompetent cells in normal mucosa. We
      sought to determine the source of antibody present in the middle ear of children.
      Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked
      immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of
      children with acute otitis media. The two-dimensional gel electrophoresis pattern
      of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid
      (MEF) was compared from the MEF and NW samples using isoelectric focusing and
      Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of
      137 children were compared. The ratio of IgG to IgA in the MEF was significantly
      different (P < 0.008) compared to NW because IgA levels were higher and IgG
      levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with
      transudation to the MEF. Small amounts of secretory IgA were detected in MEF but
      the electrophoresis patterns of the entire array of IgA antibodies in the MEF and
      NW were virtually identical in each child evaluated; thus, IgA in MEF derived
      predominantly from serum and the nasopharynx by reflux via the Eustachian tube.
      The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody
      in the MEF and NW identifies the predominant source of antibody in the MEF as a
      transudate of serum combined with nasal secretions refluxed from the nasopharynx
      in children.

PMID- 22855396
TI  - Daily quality control in CD3+ and CD4+ T cell estimation by the FACSCount system
      at a tertiary care center in south India.
AB  - CD4(+) T cell count estimations are subject to high variations; hence, in this
      study, the previous day's tested samples were included routinely as the internal
      quality controls. The percentages of variation of the 2-day values were analyzed
      for 280 observations and the mean variation for CD4(+) and CD3(+) T cell counts
      ranged from 5.21% to 9.66%. This method is a good internal quality control (IQC)
      procedure for the estimation of CD3(+) and CD4(+) T cell counts in resource-poor
      settings.

PMID- 22855397
TI  - Ultrasound-guided injection of botulinum toxin in a patient with omohyoid muscle
      syndrome: a case report.
AB  - Omohyoid muscle syndrome has a characteristic feature of a protruding lateral
      neck mass during swallowing. We present a case of omohyoid muscle syndrome
      diagnosed based on the clinical presentation and a dynamic imaging study.
      Botulinum toxin was injected into the inferior belly of one omohyoid muscle, and
      the neck mass resolved.

PMID- 22855398
TI  - Factors associated with fluoroscopy exposure during pediatric catheter ablation
      utilizing electroanatomical mapping.
AB  - PURPOSE: Exposure to ionizing radiation during electrophysiologic procedures in
      children is believed to increase the risk of future malignancy. Electroanatomical
      navigation can reduce exposure, but the cohort of children who derive the
      greatest benefit from this approach is incompletely defined. We sought to
      determine factors associated with fluoroscopy exposure with conventional catheter
      ablation versus electroanatomical navigation. METHODS: A retrospective review of
      all ablation procedures over a 5-year period during the transition to
      electroanatomical navigation performed by a single electrophysiologist was
      performed. Fluoroscopy time >20 min was considered "prolonged." Statistical
      analysis was performed to determine differences among groups. RESULTS: Two
      hundred thirty-four subjects underwent catheter ablation during the study period
      (conventional, n = 127; navigation, n = 107). Mean fluoroscopy decreased from
      11.1 to 3.5 min with electroanatomical navigation (p < 0.0001). Overall 53/107
      subjects (50 %) undergoing catheter ablation using electroanatomical navigation
      required no fluoroscopy, of which atrioventricular nodal reentry tachycardia
      (AVNRT) (n = 23) and right-sided accessory pathways (n = 22) were most common (p
      = 0.001). Prolonged fluoroscopic exposure was observed for 22/127 (17 %) subjects
      undergoing conventional fluoroscopy versus 3/107 (3 %) subjects with
      electroanatomical navigation (p = 0.001) and was not observed after increased
      experience. Flouroscopy time decreased significantly after the first 20
      procedures (p = 0.04). There was no difference in success, complication, or
      recurrence rate between groups. CONCLUSIONS: Electroanatomical navigation
      significantly reduced fluoroscopic exposure without compromising safety,
      efficacy, or recurrence. Subjects with AVNRT and right-sided accessory pathways
      derived the greatest benefit as did those requiring prolonged fluoroscopy by the
      conventional approach.

PMID- 22855399
TI  - Inference of potential genetic risks associated with large-scale releases of red
      sea bream in Kanagawa prefecture, Japan based on nuclear and mitochondrial DNA
      analysis.
AB  - Since 1978, millions of hatchery-reared red sea bream (Pagrus major) juveniles
      have been released in Sagami Bay and Tokyo Bay in Kanagawa Prefecture, Japan. The
      stock enhancement program has contributed to total catch; however, no information
      regarding the genetic interactions with wild counterparts is available. Here, we
      combined 15 microsatellite loci and mitochondrial D-loop sequencing to
      characterize the genetic resources of red sea bream in Sagami Bay and Tokyo Bay
      and to elucidate the potential harmful genetic effects associated with fish
      releases. Both types of markers evidenced higher levels of genetic diversity in
      wild samples (SB and TB) compared with offspring before stocking (H07 and H08) as
      well as a hatchery-released sample recaptured in Sagami Bay (HR). Microsatellite
      F (ST) estimates and Bayesian clustering analysis found significant genetic
      differences among samples (F (ST) = 0.013-0.054), except for the two wild samples
      (F (ST) = 0.002) and HR vs. H07 (F (ST) = 0.007). On the other hand,
      mitochondrial-based F (ST) suggested haplotypic similarity between SB, H07, and
      HR. The low effective number of females contributing to the offspring over
      multiple generations may be responsible for the lack of haplotypic
      differentiation. Moreover, the putative hatchery origin to three fish (8 %)
      without deformity in the inter-nostril epidermis was inferred for the first time.
      Our results showed the usefulness of combining nuclear and mitochondrial markers
      to elucidate genetic interactions between hatchery-released and wild red sea
      bream and warned about potential harmful genetic effects should interbreeding
      takes place.

PMID- 22855400
TI  - Isolation and characterization of male-specific DNA markers in the rock bream
      Oplegnathus fasciatus.
AB  - Sex-specific DNA markers applicable were very useful for elucidating the sex
      determination mechanism and sex control in fishes. In the present study,
      amplified fragment-length polymorphism (AFLP) approach with 144 primer
      combinations was employed to identify sex-specific markers in the rock bream.
      Four male-specific AFLP fragments were identified which were designated as
      Opl286, Opl237, Opl422, and Opl228. Further sequence analysis of the sex markers'
      genomic region revealed subtle differences between the males and females. We
      identified four male-specific single-nucleotide polymorphisms (SNPs) and a
      deletion of 8 bp in marker Opl286, six male-specific SNPs in marker Opl237, three
      male-specific SNPs in marker Opl422, and eight male-specific SNPs and 1 bp
      inversions in marker Opl228. Specific primers were designed based on the
      nucleotide variation in the sequences to develop a simple polymerase chain
      reaction method for identifying the genetic sex of rock bream. As a result, three
      out of the four male-specific markers were converted into SNP markers. The male
      specific AFLP markers and AFLP-derived SNP markers were tested in 100 individuals
      collected from three locations around the coast of Zhoushan, yielding
      reproducible sex identification. These male-specific DNA markers are a useful
      tool for the identification of the sex-determining locus in rock bream and for
      guiding artificial breeding programs.

PMID- 22855401
TI  - ESGAR 2012 Book of Abstracts.

PMID- 22855402
TI  - Development of simultaneous analysis for marker constituents in Hwangryunhaedok
      tang () and its application in commercial herbal formulas.
AB  - This study was performed to develop methods for the chromatographic determination
      of biomarkers in Hwangryunhaedok-tang (HHT) and the quantitative evaluation of
      commercial HHT. To develop an analytical method, an RP-amide column (2.7 MUm, 4.6
      * 100 mm, Halo: Supelco, Bellefonte, PA) was used with a gradient solvent system
      of mixed acetonitrile and 0.1 % phosphoric acid/water and an ultra performance
      liquid chromatography-diode array detector. The method was validated by
      specificity, linearity, accuracy (recovery) and precision tests (repeatability,
      intra and inter-day). The correlation coefficients (R (2)) of biomarkers were
      calculated as 0.9998-1.000 and their ranges were as follows: geniposide (62.5
      1,000.0 MUg/ml), berberine (31.3-500.0 mg/ml), palmatine (31.3-500.0 MUg/ml),
      baicalin (125.0-1,500.0 MUg/ml), baicalein (15.6-250.0 MUg/ml) and wogonin (5.2
      125.0 MUg/ml), respectively. The limit of detection was 0.34-4.01 MUg/ml, and the
      limit of quantification was 1.02-12.16 MUg/ml. The intra-day and inter-day
      precision of six components were revealed as 0.02-2.48 % as a relative standard
      deviation (RSD). The repeatability value of biomarkers in three different
      concentrations of HHT was 0.29-2.98 % (RSD value) and recovery was 95.72-104.90
      %. Among several extraction methods tested, biomarker content was higher with the
      20 times extraction (20TE) and mixture of extract powder (MEP) methods than with
      any other method, and some differences among diverse pharmaceutical medicines
      were revealed. The validation data indicated that the method developed is suited
      to the determination of six marker compounds in HHT. The content of biomarkers by
      simultaneous analysis was evaluated in 20TE, MEP, USA formula and Taiwan formula.

PMID- 22855404
TI  - Morphology- and phase-controlled iron oxide nanoparticles stabilized with maleic
      anhydride grafted polypropylene.

PMID- 22855403
TI  - Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally
      occurring inhibitors of cell proliferation in human leukemia HL-60 cells.
AB  - Flavonoids are widely occurring polyphenols that are found in plants. The aim of
      this study was to investigate the structure-activity relationships of 5,7
      dihydroxyflavones, with a focus on the effect of B ring structure substitution on
      the antiproliferative effects of the compounds in human leukemia HL-60 cells. We
      prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit
      the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell
      differentiation-inducing ability of the most potent flavones were investigated
      using staining and morphological analyses. This study explored the antileukemic
      and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and
      chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

PMID- 22855406
TI  - Contributions of various noncovalent bonds to the interaction between an amide
      and S-containing molecules.
AB  - N-Methylacetamide, a model of the peptide unit in proteins, is allowed to
      interact with CH(3) SH, CH(3)SCH(3), and CH(3)SSCH(3) as models of S-containing
      amino acid residues. All of the minima are located on the ab initio potential
      energy surface of each heterodimer. Analysis of the forces holding each complex
      together identifies a variety of different attractive forces, including SH???O,
      NH???S, CH???O, CH???S, SH???pi, and CH???pi H-bonds. Other contributing
      noncovalent bonds involve charge transfer into sigma* and pi* antibonds. Whereas
      some of the H-bonds are strong enough that they represent the sole attractive
      force in several dimers, albeit not usually in the global minimum, charge
      transfer-type noncovalent bonds play only a supporting role. The majority of
      dimers are bound by a collection of several of these attractive interactions. The
      SH???O and NH???S H-bonds are of comparable strength, followed by CH???O and
      CH???S.

PMID- 22855405
TI  - The mechanism of the converter domain rotation in the recovery stroke of myosin
      motor protein.
AB  - Upon ATP binding, myosin motor protein is found in two alternative conformations,
      prerecovery state M* and postrecovery state M**. The transition from one state to
      the other, known as the recovery stroke, plays a key role in the myosin
      functional cycle. Despite much recent research, the microscopic details of this
      transition remain elusive. A critical step in the recovery stroke is the rotation
      of the converter domain from "up" position in prerecovery state to "down"
      position in postrecovery state that leads to the swing of the lever arm attached
      to it. In this work, we demonstrate that the two rotational states of the
      converter domain are determined by the interactions within a small structural
      motif in the force-generating region of the protein that can be accurately
      modeled on computers using atomic representation and explicit solvent. Our
      simulations show that the transition between the two states is controlled by a
      small helix (SH1) located next to the relay helix and relay loop. A small
      translation in the position of SH1 away from the relay helix is seen to trigger
      the transition from "up" state to "down" state. The transition is driven by a
      cluster of hydrophobic residues I687, F487, and F506 that make significant
      contributions to the stability of both states. The proposed mechanism agrees well
      with the available structural and mutational studies.

PMID- 22855407
TI  - Acute right-sided colonic diverticulitis mimicking appendicitis: a report of two
      cases.
AB  - We describe two right-sided diverticulitis cases that presented with marked right
      iliac fossa tenderness with guarding and rebound and laboratory parameters
      resembling acute appendicitis. The imaging findings suggested diverticulitis in
      both cases. One of the patients underwent surgery and the other one was followed
      up with medical treatment. Awareness of these imaging findings may aid in the
      diagnosis of right-sided diverticulitis, which is frequently misdiagnosed and
      mistreated.

PMID- 22855408
TI  - New directions for therapeutics in ADHD.

PMID- 22855409
TI  - Neurohistochemistry in molluscan species: focus on extracellular matrix.
AB  - Carbohydrate polymers with acid-base properties of extracellular matrix (ECM)
      have a critical impact on guidance, migration and synaptic transmission. The
      present study showed acid-base properties of ECM stained with histochemical
      techniques. The central nervous system (CNS) of mature terrestrial slug Semperula
      maculata and freshwater bivalve Lamellidens corrianus was selected to visualize
      sulphated and carboxylic strong acid groups. Protein and carbohydrate molecules
      were found scattered in three different regions, viz. periganglionic sheath,
      along with the basement lamina, interperikaryal space including the perineuronal
      net, and neuropil, in both the molluscan species. Sulphated proteoglycans were
      abundant in periganglionic sheath of S. maculata and also occurred in the
      neuropil of L. corrianus. The interperikaryal space contained carboxyl groups
      along with hyaluronic acid, and neuropil contained abundant glycogen moiety in
      both species. Comparing the SDS-PAGE of the neural tissue extracts revealed
      protein molecules that were found in the same fraction. The ECM of neuronal cells
      from S. maculata and L. corrianus presented different kinds of glycoproteins and
      proteoglycans, which showed its morphological as well as habitual
      differentiation.

PMID- 22855410
TI  - Analyzing shoulder translation with navigation technology.
AB  - PURPOSE: Asymmetric stress imposed on the shoulder can lead to anterior shoulder
      instability in young athletes who perform repetitive overhead motions. A common
      treatment, surgical anterior capsule tightening, assumes that the instability is
      caused by abnormal anterior laxity. This study investigated the possibility that
      one element of overall imbalance, posterior capsular tightness, could be an
      underlying reason for shoulder instability. Surgical navigation technology, which
      is more accurate than whole-body motion-capture systems, was used to study
      anterior translational motions. METHOD: The study was used four cadaver
      shoulders, with the scapula and rotator cuff muscles intact. Opto-electronic
      surgical navigation localization devices were mounted on the scapula and humerus
      to accurately capture positions and orientations. The shoulders were passively
      moved through 7 motions, 5 of simple angulation and 2 combinations of clinical
      interest. Each motion was repeated in 4 different soft-tissue states: rotator
      cuff intact, capsule intact, and surgically induced capsular tightnesses of 5 and
      10mm. RESULTS: The shoulders had significantly greater anterior translation when
      the posterior capsule was artificially tightened (p < 0.05); this was
      particularly in movements that combined abduction with internal or external
      rotation, which are typical overhead sports motions. Overall translation was
      indifferent to whether the shoulders were intact or dissected down to the
      capsule, as was translation during flexion was indifferent to dissection state (p
      > 0.95). CONCLUSION: Surgical navigation technology can easily be used to analyze
      cadaveric shoulder motion, with opportunities for adaptation to anesthetized
      patients. Results suggest that the inverse of artificial tightening, such as
      surgical release of the posterior capsule, may be an effective minimally invasive
      treatment of chronic shoulder dislocation subsequent to sports motions.

PMID- 22855411
TI  - Binding of molecular magnesium hydrides to a zirconocene-enyne template.

PMID- 22855412
TI  - Avoiding diffusion limitations in cobalt(III/II)-tris(2,2'-bipyridine)-based dye
      sensitized solar cells by tuning the mesoporous TiO2 film properties.
AB  - Dye-sensitized solar cells based on electrolytes containing cobalt complexes as
      redox shuttles typically suffer a major limitation in terms of slow diffusion of
      those couples through the mesoporous TiO(2) film. This results in a drop of the
      photocurrent density, particularly at high incident light intensities, reducing
      the overall cell performance. This work illustrates how tuning the four
      characteristic parameters of the mesoporous TiO(2) layer, namely film thickness,
      particle size, pore size and porosity, by simply optimizing the TiCl(4) post
      treatment, completely eliminates diffusion problems of cobalt(III/II) tris(2,2'
      bipyridine) and at the same time maximizes the short-circuit photocurrent
      density. As a result, a power conversion efficiency of 10.0% at AM 1.5 G 100 mW
      cm(-2) was reached in conjunction with an organic sensitizer.

PMID- 22855413
TI  - Pathological features of oxalate nephrosis in a population of koalas
      (Phascolarctos cinereus) in South Australia.
AB  - The wild and captive koala population of the Mt Lofty Ranges in South Australia
      has a high level of renal dysfunction in which crystals consistent with calcium
      oxalate have been observed in the kidneys. This study aimed to describe the
      pathological features of the renal disease in this population, confirm the
      composition of renal crystals as calcium oxalate, and determine whether any age
      or sex predispositions exist for this disease. A total of 51 koalas (28 wild
      rescues, 23 captive) were examined at necropsy, of which 28 (55%) were found to
      have gross and/or histological evidence of oxalate nephrosis. Histopathological
      features included intratubular and interstitial inflammation, tubule dilation,
      glomerular atrophy, tubule loss, and cortical fibrosis. Calcium oxalate crystals
      were demonstrated using a combination of polarization microscopy, alizarin red S
      staining, infrared spectroscopy, and energy-dispersive X-ray analysis with
      scanning electron microscopy. Uric acid and phosphate deposits were also shown to
      be present but were associated with minimal histopathological changes. No
      significant differences were found between the numbers of affected captive and
      wild rescued koalas; also, there were no sex or age predispositions identified,
      but it was found that oxalate nephrosis may affect koalas <2 years of age. The
      findings of this study suggest that oxalate nephrosis is a leading disease in
      this koala population. Possible causes of this disease are currently under
      investigation.

PMID- 22855414
TI  - Comment on Masek-Hammerman et al, "epizootic myocarditis associated with
      encephalomyocarditis virus in a group of rhesus macaques (Macaca mulatta)," Vet
      Pathol. 2012;49:386-392.

PMID- 22855416
TI  - The effectiveness of erythromycin in reducing stent-related tissue hyperplasia:
      an experimental study with a rat esophageal model.
AB  - BACKGROUND: Erythromycin is not only a potent antibiotic; it also has effects of
      reduction of inflammation and suppression of protein synthesis. PURPOSE: To
      evaluate the impact of erythromycin on tissue hyperplasia after stent placement
      in a rat esophageal model. MATERIAL AND METHODS: A total of 21 rats were
      included. After placement of self-expanding stents in the mid esophagus, the rats
      were divided into two experimental groups and one control group. The rats in the
      experimental groups received daily intraperitoneal injections of erythromycin for
      5 weeks; 4 mg/kg (group A, n = 7) and 8 mg/kg (group B, n = 7). Those in the
      control group (n = 7) received 1 mL of saline intraperitoneally. After sacrifice,
      histologic analysis was done for thickness of the papillary projection,
      granulation tissue area, percentage of granulation tissue area, and degree of
      inflammatory cell infiltration. The statistical significance of differences
      between groups was assessed by Mann-Whitney U test. RESULTS: Tissue hyperplasia
      as reflected in thickness of papillary projection, granulation tissue area, and
      percentage of granulation tissue area, was higher in the control group than in
      the experimental groups, although there was no statistical significance (P =
      1.00, 0.332, and 0.263, respectively). However, degree of inflammatory cell
      infiltration was significantly lower in the experimental groups than the control
      group (P = 0.025), and the higher dosage of erythromycin reduced inflammatory
      cell infiltration significantly (P = 0.037). CONCLUSION: Intraperitoneal
      administration of erythromycin is very effective in reducing inflammation after
      stent placement in a rat esophageal model but has no significant effect on
      granulation tissue formation.

PMID- 22855415
TI  - Bicarbonate efflux via GABA(A) receptors depolarizes membrane potential and
      inhibits two-pore domain potassium channels of astrocytes in rat hippocampal
      slices.
AB  - Increasing evidence indicates the functional expression of ionotropic gamma
      aminobutyric acid receptor (GABA(A) -R) in astrocytes. However, it remains
      controversial in regard to the intracellular Cl(-) concentration ([Cl(-) ](i) )
      and the functional role of anion-selective GABA(A) -R in astrocytes. In
      gramicidin perforated-patch recordings from rat hippocampal CA1 astrocytes, GABA
      and GABA(A) -R-specific agonist THIP depolarized astrocyte membrane potential
      (V(m) ), and the THIP-induced currents reversed at the voltages between -75.3 and
      -78.3 mV, corresponding to a [Cl(-) ](i) of 3.1-3.9 mM that favored a passive
      distribution of Cl(-) anions across astrocyte membrane. Further analysis showed
      that GABA(A) -R-induced V(m) depolarization was ascribed to HCO(3) (-) efflux,
      while a passively distributed Cl(-) mediated no net flux or influx of Cl(-) that
      leads to an unchanged or hyperpolarized V(m) . In addition to a rapidly activated
      GABA(A) -R current component, GABA and THIP also induced a delayed inward current
      (DIC) in 63% of astrocytes. The DIC became manifest after agonist withdrawal and
      enhanced in amplitude with increasing agonist application duration or
      concentrations. Astrocytic two-pore domain K(+) channels (K2Ps), especially TWIK
      1, appeared to underlie the DIC, because (1) acidic intracellular pH, as a result
      of HCO(3) (-) efflux, inhibited TWIK-1, (2) the DIC remained in the Cs(+)
      recording solutions that inhibited conventional K(+) channels, and (3) the DIC
      was completely inhibited by 1 mM quinine but not by blockers for other
      cation/anion channels. Altogether, HCO(3) (-) efflux through activated GABA(A) -R
      depolarizes astrocyte V(m) and induces a delayed inhibition of K2Ps K(+) channels
      via intracellular acidification.

PMID- 22855417
TI  - Safety and efficacy of splenic artery coil embolization for hypersplenism in
      liver cirrhosis.
AB  - BACKGROUND: Partial splenic artery embolization is an effective treatment for
      hypersplenism but often lacks long-term benefits. PURPOSE: To evaluate the long
      term effects of coil embolization of the splenic artery in patients with liver
      cirrhosis and hypersplenism. MATERIAL AND METHODS: Forty-nine patients with liver
      cirrhosis and hypersplenism underwent coil embolization of the main splenic
      artery. The coils were deployed in the mid- or distal segment of the splenic
      artery to allow collateral blood flow to the spleen. The following data were
      collected from 2 weeks to 4 years after the embolization: technical success,
      length of hospital stay, white blood cell count, platelet count, splenic volume,
      and complication. RESULTS: The technical success rate of splenic artery coil
      embolization was 100%. The post embolization syndrome rate was 75% (36/49) with
      no incidence of major complications. The mean length of hospital stay was 9 days.
      After embolization, the patient's white blood and platelet counts increased
      significantly, peaked at 2 weeks, and gradually decreased during the 4-year
      follow-up period, but remained at significantly higher levels than pre
      embolization levels. Follow-up CT scans demonstrated a gradual increase in the
      volume of the enhanced portions of the spleens with a decrease in the volume of
      unenhanced portion. No significant changes occurred in the red blood cell count
      and liver function after the embolization. CONCLUSION: Embolization of the mid
      and distal main splenic artery with coils is a safe and effective treatment of
      hypersplenism in cirrhosis with long-term hematologic benefits.

PMID- 22855418
TI  - Can segmented 3D images be used for stenosis evaluation in coronary CT
      angiography?
AB  - BACKGROUND: Thanks to the development of computed tomography (CT) scanners and
      computer software, accurate coronary artery segmentation can be achieved with
      minimum user interaction. However, the question remains whether we can use these
      segmented images for reliable diagnosis. PURPOSE: To retrospectively evaluate the
      diagnostic accuracy of coronary CT angiography (CCTA) using segmented 3D data for
      the detection of significant stenosis. MATERIAL AND METHODS: CCTA data-sets from
      30 patients were acquired with a 64-slice CT scanner and segmented using the
      region growing (RG) method and the "virtual contrast injection" (VC) method.
      Three types of images of each patient were reviewed by different reviewers for
      the presence of stenosis with diameter reduction of 50% or more. The evaluation
      was performed on four main arteries of each patient (120 arteries in total). For
      the original series, the reviewer was allowed to use all the 2D and 3D
      visualization tools available (conventional method). For the segmented results
      from RG and VC, only maximum intensity projection was used. Evaluation results
      were compared with catheter angiography (CA) for each artery in a blinded
      fashion. RESULTS: Overall, 34 arteries with significant stenosis were identified
      by CA. The percentage of evaluable arteries, accuracy and negative predictive
      value for detecting stenosis were, respectively, 86%, 74%, and 93% for the
      conventional method, 83%, 71%, and 92% for VC, and 64%, 56%, and 93% for RG.
      Accuracy was significantly lower for the RG method than for the other two methods
      (P < 0.01), whereas there was no significant difference in accuracy between the
      VC method and the conventional method (P = 0.22). CONCLUSION: The diagnostic
      accuracy for the RG-segmented 3D data is lower than those with access to 2D
      images, whereas the VC method shows diagnostic accuracy similar to the
      conventional method.

PMID- 22855419
TI  - Bile aspiration and hydrodissection to prevent complications in hepatic RFA close
      to the gallbladder.
AB  - BACKGROUND: Radiofrequency ablation (RFA) of liver tumors is a mainstay of
      interventional oncology. Its application, however, is limited by tumor size and
      location with lesions located within 1 cm to the gallbladder being at increased
      risk for complications. PURPOSE: To evaluate the safety of hepatic RFA after bile
      aspiration with or without additional hydrodissection for lesions adjacent to the
      gallbladder. MATERIAL AND METHODS: Six patients undergoing RFA of tumors with a
      distance of less than 1 cm to the gallbladder were retrospectively identified
      from a computer database. All patients underwent RFA combined with percutaneous
      bile aspiration from the gallbladder. In four patients additional hydrodissection
      was performed. Technical success and post-interventional complications were
      assessed by reviewing images and patient charts. RESULTS: Ablations were
      successfully completed in 5/6 patients. In one patient with incomplete ablation
      re-ablation was performed 2 months after the initial procedure. Minor
      complications occurred in three patients, including right-sided pleural effusion,
      hematoma in the gallbladder fossa, and intralesional hemorrhage in one patient
      each. There were no cases with cholecystitis or damage to the gallbladder during
      follow-up. CONCLUSION: Bile aspiration with or without additional hydrodissection
      permits safe RFA of tumors located close to the gallbladder.

PMID- 22855420
TI  - Sonographic findings in two cases of complicated pregnancy in women previously
      treated with endometrial ablation.
AB  - When medical therapy fails for menorrhagia in a premenopausal woman, minimally
      invasive endometrial ablation can be used as a conservative management
      alternative to hysterectomy. Endometrial ablation alone is not considered
      effective contraception, and women of reproductive age can become pregnant after
      ablative therapy. We now present two cases of pregnancy after endometrial
      ablation and associated imaging where both cases required cesarean hysterectomy
      due to post-partum hemorrhage. Pregnancy after endometrial ablation incurs
      increased morbidity and diagnostic dilemmas.

PMID- 22855421
TI  - Electron capture dissociation of hydrogen-deficient peptide radical cations.
AB  - Hydrogen-deficient peptide radical cations exhibit fascinating gas phase
      chemistry, which is governed by radical driven dissociation and, in many cases,
      by a combination of radical and charge driven fragmentation. Here we examine
      electron capture dissociation (ECD) of doubly, [M + H](2+*), and triply, [M +
      2H](3+*), charged hydrogen-deficient species, aiming to investigate the effect of
      a hydrogen-deficient radical site on the ECD outcome and characterize the
      dissociation pathways of hydrogen-deficient species in ECD. ECD of [M + H](2+*)
      and [M + 2H](3+*) precursor ions resulted in efficient electron capture by the
      hydrogen-deficient species. However, the intensities of c- and z-type product
      ions were reduced, compared with those observed for the even electron species,
      indicating suppression of N-C(alpha) backbone bond cleavages. We postulate that
      radical recombination occurs after the initial electron capture event leading to
      a stable even electron intermediate, which does not trigger N-C(alpha) bond
      dissociations. Although the intensities of c- and z-type product ions were
      reduced, the number of backbone bond cleavages remained largely unaffected
      between the ECD spectra of the even electron and hydrogen-deficient species. We
      hypothesize that a small ion population exist as a biradical, which can trigger N
      C(alpha) bond cleavages. Alternatively, radical recombination and N-C(alpha) bond
      cleavages can be in competition, with radical recombination being the dominant
      pathway and N-C(alpha) cleavages occurring to a lesser degree. Formation of b-
      and y-type ions observed for two of the hydrogen-deficient peptides examined is
      also discussed.

PMID- 22855422
TI  - Dual-function CXCR4 antagonist polyplexes to deliver gene therapy and inhibit
      cancer cell invasion.

PMID- 22855423
TI  - Cranial roots of the accessory nerve exist in the majority of adult humans.
AB  - The inclusion of a cranial root as a component of the accessory nerve is
      controversial with at least one recent study claiming that intracranial rootlets
      do not exist in humans. In response to this debate, the present study aimed to
      clarify this anatomy in a large cadaveric sample. In this study, 43 adult
      cadavers (86 sides) were dissected via a posterior approach to the craniocervical
      junction. Observations were made for the presence or absence of cranial roots of
      the accessory nerve, and when present, their lengths and diameters were measured.
      Relationships of these rootlets were documented. A cranial root of the accessory
      nerve was identified in 76% of sides. When identified, 1-6 cranial rootlets (mean
      4.5) of the accessory nerve were observed. They ranged in diameter from 0.1 to
      1.1 mm (mean 0.7 mm). The length of these nerves ranged from 8 to 24 mm with a
      mean of 17 mm. In general, the more superior rootlets were shorter and the more
      inferior rootlets were longer. Although there was a slight tendency for the
      cranial roots to be more numerous and larger on right sides and in males, this
      did not reach statistical significance. We believe this to be the largest study
      to date documenting the presence of a cranial root of the accessory nerve. Based
      on our findings, a cranial root exists in the majority of specimens.
      Neurosurgical procedures or high quality imaging of this area should enable the
      physician to see these structures.

PMID- 22855424
TI  - Umbilical venous blood flow and its measurement in the human fetus.
AB  - In this review, we evaluate the published methodologies to describe a noninvasive
      technique for the quantitative assessment of umbilical venous blood flow in the
      human fetus. We identify a number of variations in the reported methodologies and
      address some of the common errors associated with Doppler assessment of umbilical
      venous flow volume. The potential role of umbilical venous flow volumetry in the
      management of intrauterine growth restriction is briefly evaluated including its
      utility and reliability in everyday clinical practice.

PMID- 22855425
TI  - Preparation and characterization of Mg-Zr mixed oxide aerogels and their
      application as aldol condensation catalysts.
AB  - A series of Mg-Zr mixed oxides with different nominal Mg/(Mg+Zr) atomic ratios,
      namely 0, 0.1, 0.2, 0.4, 0.85, and 1, is prepared by alcogel methodology and
      fundamental insights into the phases obtained and resulting active sites are
      studied. Characterization is performed by X-ray diffraction, transmission
      electron microscopy, X-ray photoelectron spectroscopy, N(2) adsorption-desorption
      isotherms, and thermal and chemical analysis. Cubic Mg(x)Zr(1-x)O(2-x) solid
      solution, which results from the dissolution of Mg(2+) cations within the cubic
      ZrO(2) structure, is the main phase detected for the solids with theoretical
      Mg/(Mg+Zr) atomic ratio <=0.4. In contrast, the cubic periclase (c-MgO) phase
      derived from hydroxynitrates or hydroxy precursors predominates in the solid with
      Mg/(Mg+Zr)=0.85. c-MgO is also incipiently detected in samples with
      Mg/(Mg+Zr)=0.2 and 0.4, but in these solids the c-MgO phase mostly arises from
      the segregation of Mg atoms out of the alcogel-derived c-Mg(x)Zr(1-x)O(2-x) phase
      during the calcination process, and therefore the species c-MgO and c-Mg(x)Zr(1
      x)O(2-x) are in close contact. Regarding the intrinsic activity in furfural
      acetone aldol condensation in the aqueous phase, these Mg-O-Zr sites located at
      the interface between c-Mg(x)Zr(1-x)O(2-x) and segregated c-MgO display a much
      larger intrinsic activity than the other noninterface sites that are present in
      these catalysts: Mg-O-Mg sites on c-MgO and Mg-O-Zr sites on c-Mg(x)Zr(1-x)O(2
      x). The very active Mg-O-Zr sites rapidly deactivate in the furfural-acetone
      condensation due to the leaching of active phases, deposition of heavy
      hydrocarbonaceous compounds, and hydration of the c-MgO phase. Nonetheless, these
      Mg-Zr materials with very high specific surface areas would be suitable solid
      catalysts for other relevant reactions catalyzed by strong basic sites in
      nonaqueous environments.

PMID- 22855426
TI  - Brentuximab vedotin in transplant-naive patients with relapsed or refractory
      hodgkin lymphoma: analysis of two phase I studies.
AB  - BACKGROUND: Brentuximab vedotin is an antibody-drug conjugate designed to
      selectively deliver monomethyl auristatin E, a microtubule-disrupting agent, to
      CD30-expressing cells. Brentuximab vedotin induces durable objective responses in
      patients with relapsed or refractory Hodgkin lymphoma (HL) after autologous stem
      cell transplantation (ASCT). The objective of this post-hoc analysis was to
      characterize the safety and efficacy of brentuximab vedotin for patients with
      relapsed or refractory HL who refused or were ineligible for ASCT. METHODS: This
      case series included 20 transplant-naive patients who were enrolled in two phase
      I multicenter studies. Patients received brentuximab vedotin intravenously every
      3 weeks or every week for 3 out of 4 weeks. RESULTS: The majority of patients
      were transplant-naive because of chemorefractory disease. Median age was 31.5
      years (range, 12-87 years). Treatment-emergent adverse events in >20% of patients
      were peripheral neuropathy, fatigue, nausea, pyrexia, diarrhea, weight decreased,
      anemia, back pain, decreased appetite, night sweats, and vomiting; most events
      were grade 1 or 2. Six patients obtained objective responses: two complete
      remissions and four partial remissions. Median duration of response was not met;
      censored durations ranged from >6.8 to >13.8 months. Three of six responders
      subsequently received ASCT. CONCLUSION: Brentuximab vedotin was associated with
      manageable adverse events in transplant-naive patients with relapsed or
      refractory HL. The objective responses observed demonstrate that antitumor
      activity is not limited to patients who received brentuximab vedotin after ASCT.
      The promising activity observed in this population warrants further study.

PMID- 22855427
TI  - Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas.
AB  - The concept that tumors are maintained by dedicated stem cells, the so-called
      cancer stem cell hypothesis, has attracted great interest but remains
      controversial. Studying mouse models, we provide direct, functional evidence for
      the presence of stem cell activity within primary intestinal adenomas, a
      precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre
      reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5
      (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein
      coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the
      growth of established intestinal adenomas. These Lgr5(+) cells, which represent
      about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as
      well as all other adenoma cell types. The Lgr5(+) cells are intermingled with
      Paneth cells near the adenoma base, a pattern reminiscent of the architecture of
      the normal crypt niche.

PMID- 22855428
TI  - The hands shield attention from visual interference.
AB  - Recent investigations have revealed enhanced processing of information that is
      presented within hand space. A potential consequence of such enhancement could be
      that simultaneous processing of information outside of hand space is diminished,
      but this possibility has yet to be tested. Here, we considered the possibility
      that the hands can serve as a natural remedy for unwanted interference, by acting
      as a physical manifestation of the attentional window. Participants performed a
      flanker task in which they identified a central target letter in the presence of
      flanking letters that varied in their degrees of compatibility with the target.
      Participants either held their hands around the target, such that the flankers
      appeared outside of the hands (but in clear view), or held their hands away from
      the display, and thus not around any of the stimuli. Flanker interference was
      markedly reduced when the hands were around the target, and these effects were
      not attributable to visual differences across the conditions. Collectively, these
      results indicate that the hands effectively shield attention from visual
      interference.

PMID- 22855429
TI  - Overcoming the limitations of lithiation chemistry for organoboron compounds with
      continuous processing.

PMID- 22855430
TI  - The Monro Bell controversy.
AB  - Amongst the contributions in anatomy and surgery of the celebrated Monros was the
      contentious "discovery" by Monro Secundus of the interventricular foramen.
      Monro's account (1783) was vehemently criticized in London, especially by Charles
      Bell for presuming to describe something which was already well known and for
      inaccuracies. Monro with some justification in 1797 disputed this attack,
      although his anatomical description was shown by later anatomists to be mistaken.

PMID- 22855431
TI  - Contrast-enhanced ultrasound findings in a case of renal extramedullary
      hematopoiesis.
AB  - We present the case of an 80-year-old man with two renal solid masses found at
      sonography, which were imaged by contrast-enhanced ultrasound, CT, and MRI and
      confirmed histologically. Contrast-enhanced ultrasound findings suggested a
      benign mass and a CT-guided biopsy yielded a diagnosis of extramedullary
      hematopoiesis.

PMID- 22855432
TI  - Activation of carbon dioxide over zinc oxide by localised electrons.
AB  - The unique mechanism of activation of carbon dioxide over zinc oxide is
      unravelled using advanced quantum mechanical methods. The key process is the
      CO(2)  chemisorption catalysed by a highly localized electron carrier trapped at
      a vacant oxygen interstitial surface site. At the top of the reaction barrier
      CO(2)  pulls the electron from the vacancy and thus becomes active.

PMID- 22855435
TI  - Catalytic asymmetric synthesis of alpha-quaternary proline derivatives by 1,3
      dipolar cycloaddition of alpha-silylimines.

PMID- 22855434
TI  - Transient reactivation of occult hepatitis B virus infection despite lamivudine
      prophylaxis in a patient treated for non-Hodgkin lymphoma.
AB  - A female patient with non-Hodgkin lymphoma who tested positive for surface
      antigen of the hepatitis B virus and negative for hepatitis B core antibody
      experienced a reactivation of occult HBV infection 20 months after rituximab
      discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab
      administration and the subsequent 12 months.

PMID- 22855433
TI  - Chlamydia trachomatis prevalence, genotype distribution and identification of the
      new Swedish variant in Southern Germany.
AB  - PURPOSE: In Germany, reliable data about the prevalence of urogenital Chlamydia
      trachomatis infections, causative genotypes, as well as corresponding clinical,
      demographic and behavioural information are sparse. We, therefore, performed a
      prospective prevalence study including 1,003 sexually active volunteers of a
      Southern German city. METHODS: Study participants completed a standardised
      questionnaire and provided first void urine samples for analysis. Our screening
      strategy included the performance of two nucleic acid amplification tests with
      different target genes, enabling the detection of the new Swedish variant of C.
      trachomatis (nvCT). Direct genotyping of positive specimens was performed by
      sequence analysis of the ompA gene. RESULTS AND CONCLUSION: The overall
      prevalence of C. trachomatis infection was 4.2 % in women and 4.6 % in men. A
      relatively high prevalence of 8.3 % was found in men older than 25 years. Never
      using condoms was an independent risk factor for infection. The most common
      symptom was discharge; however, 64.5 % of infected females and all of the
      infected men were asymptomatic, supporting the need for screening programmes. The
      most frequently encountered genotypes were E (46.5 %), F (20.9 %) and K (14.0 %).
      Since the nvCT was detected in one female student, this is one of the rare
      studies that reports on the molecular identification of nvCT apart from Sweden.

PMID- 22855436
TI  - Gene L. Colborn (1935-2011).

PMID- 22855437
TI  - Usefulness of transesophageal echocardiography during implantation of the
      CoreValve percutaneous aortic prosthesis: influence of the learning curve.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the
      usefulness of transesophageal echocardiography during the implantation of the
      CoreValve percutaneous aortic prosthesis and the influence of the learning curve
      in its indications. METHODS: From April 2008 to January 2010, 53 patients were
      treated for symptomatic severe aortic stenosis with a CoreValve percutaneous
      aortic prosthesis. Transesophageal echocardiography was performed during the
      procedure for two reasons: if a discrepancy between the measures of the aortic
      annulus arose before the implantation and to provide visualization if a
      complication occurred during the procedure. Patients were divided in to two
      groups based on the learning curve (group I:the first 25 patients, group II: all
      of the subsequent patients). RESULTS: Thirty-six transesophageal
      echocardiographies were performed on 28 patients (53%).In 15 cases the indication
      was to assist us in determining the proper sized prosthesis, and in the other 21
      cases it was performed due to a complication during the procedure. The numbers of
      intraprocedure transesophageal echocardiographies were similar in both learning
      curve groups, (64% in group I vs. 71% in group II, P = 0.56) but the proportion
      of the studies indicated by serious complications was significantly lower in the
      second period of the learning curve (67% in group I vs. 17% in group II, P <
      0.05). CONCLUSIONS: In our experience, transesophageal echocardiography was very
      useful in more than one-half of the patients during the implantation of the
      CoreValve percutaneous aortic prosthesis. After overcoming the learning curve,
      its indication due to serious procedure-related complications decreased
      significantly.

PMID- 22855438
TI  - Simple, but challenging: recent developments in the asymmetric synthesis of
      spiroketals.

PMID- 22855439
TI  - The supratrochlear foramen of the humerus in a South African dry bone sample.
AB  - The supratrochlear foramen (STF) of the humerus is the aperture that forms when
      the septum separating the coronoid and olecranon fossa is perforated. There are
      no known studies in the literature on the STF among various South African ethnic
      groups. The presence and shapes of the STF were established by visual observation
      from a sample of 538 skeletonized individuals with paired humeri (1,076) and of
      equal numbers between the sexes. Measurements of the transverse (TD) and vertical
      (VD) distance of the STF were obtained using extended jaw calipers. An
      osteometric board was used to measure the epicondylar breadth (EB). Sliding
      calipers were used to measure the distance of the medial epicondyle to medial
      aspect of the STF (MB) and that of the lateral epicondyle to lateral border of
      the STF (LB). The prevalence of STF in the South African population was 32.5% and
      predominantly on the left with the highest incidence among the Sotho population
      (41%) and the lowest incidence in Whites (16%). Females (19.5%) had a higher
      frequency of the STF compared with males (13%). The STF occurred in oval (136),
      round (77), triangular (9), and irregular (34) shapes. The average EB in this
      study was 56.1 mm, whereas the average MB and LB were 25.4 mm and 26.3 mm,
      respectively. The average TD was 6.3 mm and average VD was 4.3 mm. These findings
      may be of clinical significance to surgeons and osteologists and may have
      anthropological or forensic importance.

PMID- 22855440
TI  - [Geographic patterns and ecological factors correlates of snake species richness
      in China].
AB  - Understanding large-scale geographic patterns of species richness as well its
      underlying mechanisms are among the most significant objectives of macroecology
      and biogeography. The ecological hypothesis is one of the most accepted
      explanations of this mechanism. Here, we studied the geographic patterns of
      snakes and investigated the relationships between species richness and ecological
      factors in China at a spatial resolution of 100 km*100 km.  We obtained the
      eigenvector-based spatial filters by Principal Coordinates Neighbor Matrices, and
      then analyzed ecological factors by multiple regression analysis. The results
      indicated several things: (1) species richness of snakes showed multi-peak
      patterns along both the latitudinal and longitudinal gradient. The areas of
      highest richness of snake are tropics and subtropical areas of Oriental realm in
      China while the areas of lowest richness are Qinghai-Tibet Plateau, the
      grasslands and deserts in northern China, Yangtze-Huai Plain, Two-lake Plain, and
      the Poyang-lake Plain; (2) results of multiple regression analysis explained a
      total of 56.5% variance in snake richness. Among ecological factors used to
      explore the species richness patterns, we found the best factors were the
      normalized difference vegetation index, precipitation in the coldest quarter and
      temperature annual range ; (3) our results indicated that the model based on the
      significant variables that (P<0.05) uses a combination of precipitation of
      coldest quarter, normalized difference vegetation index and temperature annual
      range is the most parsimonious model for explaining the mechanism of snake
      richness in China. This finding demonstrates that different ecological factors
      work together to affect the geographic distribution of snakes in China. Studying
      the mechanisms that underlie these geographic patterns are complex, so we must
      carefully consider the choice of impact-factors and the influence of human
      activities.

PMID- 22855441
TI  - [Population and distribution of the Siberian crane (Grus leucogeranus) wintering
      in the Poyang lakes over the past decade].
AB  - Using simultaneous land surveys, we monitored the population size and spatial
      distribution of wintering Siberian cranes at 64 lakes around Poyang Lake between
      1998 and 2010. The results showed that 46 lakes were inhabited by wintering
      cranes, and in 25 of those, the number of wintering cranes accounted for more
      than 1% of the Siberian cranes' global population. The lakes where over 40.0% of
      the global population, e.g. 1 280 individuals, included Dachahu Lake in Jiujiang
      region, and Banghu Lake and Candouhu Lake in the Poyang Lake Nature Reserve. The
      average yearly population of the wintering Siberian crane in the Poyang lakes was
      3 108+/-849, with the maximum of 4 004 individuals in winter 2002. On the whole,
      there was no drastic fluctuation, but population numbers have shown considerable
      fluctuation since 2003. We also found the Poyang Lake Nature Reserve was the
      major wintering area of the Siberian crane, with over 60% of Siberian cranes
      wintering in the reserve since 2002 (except in 2006). Most of the inhabited lakes
      are covered in existing nature reserves, though some lakes outside the reserve
      were also considerably used by Siberian cranes.

PMID- 22855442
TI  - [Protocadherin alpha gene cluster is required for myelination and oligodendrocyte
      development].
AB  - This work used Immunohistochemistry to examine the expression of myelin basic
      protein and accumulation of oligodendrocytes in Pchdalpha knockout and control
      littermate mice. Data showed that in Pchdalpha knockout mice, Myelin proteins
      decrease in the central nervous system and mature oligodendrocytes in the
      cerebellum also decrease. Furthermore, deletion of the Pcdhalpha cluster does not
      cause any change to the axons and astrocytes in quantification of relative marker
      proteins. These findings suggest that the Pcdhalpha cluster may be required for
      myelination and oligodendrite development of the brain in mice, and that
      Pcdhalpha cluster may play a key role in the development of the central nervous
      system.

PMID- 22855443
TI  - [Effects of resistin on hepatic fibrosis: possible mechanisms in non-alcoholic
      fatty liver disease in in vitro and in vivo].
AB  - To investigate the effects and possible mechanisms of resistin on hepatic
      fibrosis in non-alcoholic fatty liver disease, this review used an in vivo model
      utilizing Wistar rats with a high fat diet. Recombinant resistin was selected to
      play role in hepatic stellate cells in the HSC-T6 cell line. We observed the
      degrees of hepatic fibrosis, measured the levels of Liver fibrosis spectrum and
      detected expression levels of resistin mRNA and protein in liver tissue as well
      as the expression levels of TGFbeta-1 and TNF-alpha mRNA in HSC-T6. The results
      showed that expression of resistin in rat liver tissue and the degree of hepatic
      fibrosis increased over time with a high fat diet. Along with the increased
      concentration of resistin and levels of fibrosis index, TGFbeta-1and TNF-alpha
      also increased in HSC-T6 cells. Compared with the control group, significant
      differences were found between each group, suggesting resistin by proinflammatory
      cytokine TNF-alpha and TGF-beta1 induced the occurrence and development of NAFLD
      in hepatic fibrosis.

PMID- 22855444
TI  - [Evolutionary stability analysis of asymmetric hawk-dove game considering the
      impact of common resource].
AB  - Explaining the evolution of cooperation remains one of the important problems in
      both biology and social science. Classical theories mainly based on an assumption
      that cooperative players are symmetrically interacted. However, almost all the
      well-studied systems showed that cooperative players are in fact asymmetrically
      interacted and that asymmetric interaction might greatly affect cooperation
      behavior of the involved players. Considering the asymmetric interaction and the
      selection pressure of resources, we present a model that possesses four
      strategies: strength- cooperation (SC), strength-defection (SD), weakness
      cooperation (WC) and weakness-defection (WD). Combining evolutionary game theory
      with dynamical stability theory, we find that the evolutionary results closely
      depend on the asymmetric interaction and selection pressure of resources as well
      as cost-to-benefit ratio of conflict. When the common resources are plentiful,
      the cost-to-benefit ratio of conflict is negatively correlated with the
      probability of SC, while it is positively correlated with the probability of SD
      and WD. With increasing the strength ratio between the strong and weak players,
      the proportion of SC and SD will increase, while the proportion of WD will
      reduce. The model developed here has intrinsically integrated Boxed Pigs game and
      Hawk-Dove game. When the common resource is at shortage, the Boxed Pigs game will
      transform into Hawk-Dove game under the increase of the strength ratio between
      the strong and weak players.

PMID- 22855445
TI  - [Cloning and expression of Tssk1 & Tssk2 in mice and the presence & localization
      of them in mature sperm].
AB  - We sought to experimentally verify if testis specific serine/threonine kinases
      (Tssks) play a role in spermatogenesis and/or the regulation of sperm function.
      Purified Tssk proteins were obtained based on cloning and expression of mouse
      Tssk1 and Tssk2. Tssk1 and Tssk2 were detected in mature mouse and human sperm by
      western blotting. Immunofluorescence indicated that Tssk1 is distributed in the
      acrosome and the entire flagellum of mouse sperm while Tssk2 was mainly
      distributed in post-acrosomal region. There was no alteration in the distribution
      pattern of Tssk1 and Tssk2 in non-capacitated and capacitated sperm. Tssk2
      distribution remained unchanged after induced acrosome reaction but no signals
      were detected in the acrosome for Tssk1, which was present before the acrosome
      reaction, though signals in flagellum were undisturbed. In human sperm, Tssk1 was
      found in neck and flagellum while Tssk2 was found in the equatorial region. Our
      results suggest Tssk1 and/or Tssk2 do play an important role(s) in the regulation
      of sperm function.

PMID- 22855446
TI  - [Phylogenetic analysis and expression patterns of tropomyosin in amphioxus].
AB  - In amphioxus, we found a mesoderm related gene, tropomyosin, which encodes a
      protein comprising 284 amino acid residues, sharing high identities with other
      known Tropomyosin proteins both in vertebrates and invertebrates.
      Phylogenetically, amphioxus Tropomyosin fell outside the invertebrate clade and
      was at the base of the vertebrate protein family clade, indicating that it may
      represent an independent branch. From the early neurula to the larva stage, whole
      mount in situ hybridization and histological sections found transcripts of
      amphioxus tropomyosin gene. Weak tropomyosin expression was first detected in the
      wall of the archenteron at about 10 hours-post-fertilization neurula stage, while
      intense expression was revealed in the differentiating presumptive notochord and
      the muscle. Transcripts of tropomyosin were then expressed in the formed
      notochord and somites. Gene expression seemed to continue in these developing
      organs throughout the neurular stages and remained till 72-hours, during the
      early larval stages. In situ study still showed tropomyosin was also expressed in
      the neural tube, hepatic diverticulum, notochord and the spaces between myotomes
      in adult amphioxus. Our results indicated that tropomyosin may play an important
      role in both embryonic development and adult life.

PMID- 22855447
TI  - [Molecular cloning of tubulin beta 3 (TUBB3) in Gekko japonicus and preparation
      of its polyclonal antibody].
AB  - The tubulin beta III (TUBB3) gene encodes a class III member of the beta tubulin
      protein family that is primarily expressed in neurons and is considered to play a
      critical role in proper axon guidance and maintenance. This protein is generally
      used as a specific marker of neurons in the central nervous system. We obtained
      the full length cDNA sequence of TUBB3 by using the RACE method based on the EST
      fragment from the brain and spinal cord cDNA library of Gekko japonicus. We
      further investigated the multi-tissue expression pattern by RT-PCR and identified
      one transcript of TUBB3 about 1.8 kb in the central nervous system of Gekko
      japonicus by Northern blotting. The completed cDNA of gecko TUBB3 is 1 790 bp
      with an open reading frame of 1 350 bp, encoding a 450 amino-acid protein. The
      recombinant plasmid of pET-32a-TUBB3 was constructed and induced to express His
      tagged TUBB3 protein in prokaryotic BL21 cells. The purified TUBB3 protein was
      then used to immunize rabbits to generate polyclonal antisera. The titer of the
      antiserum was more than 1:65 536 determined by ELISA. The result of western
      blotting showed that the TUBB3 antibody could specifically recognize the
      recombinant TUBB3 protein and endogenous TUBB3 protein. Our findings provide the
      tools to further understand the TUBB3 gene and investigate the regeneration of
      the central nervous system in Gekko japonicas.

PMID- 22855448
TI  - [Polymorphisms of inhibin alpha gene exon 1 in buffalo (Bubalus bubalis), gayal
      (Bos frontalis) and yak (Bos grunniens)].
AB  - To elucidate the genetic characteristics of the bovine Inhibin alpha subunit
      (INHA) gene, the polymorphisms in exon 1 of INHA and its bilateral sequences were
      assayed using PCR with direct sequencing in buffalo, gayal and yak. A comparative
      analysis was conducted by pooled the results in this study with the published
      data of INHA on some mammals including some bovine species together. A synonymous
      substitution c.73C>A was identified in exon 1 of INHA for buffalo, which results
      in identical encoding product in river and swamp buffalo. In gayal, two non
      synonymous but same property substitutions in exon 1 of INHA, viz. c.62 C>T and
      c.187 G>A, were detected, which lead to p. P21L, p. V63M changes in INHA,
      respectively. In yak, nucleotide substitution c.62C> T, c.129A>G were found in
      exon 1 of INHA, the former still causes p. P21L substitution and the latter is
      synonymous. For the sequence of the 5'-flanking region of INHA examined, no SNPs
      were found within the species, but a substitution, c. -6T>G, was found. The
      nucleotide in this site in gayal, yak and cattle was c. -6G, whereas in buffalo
      it was c. -6T. Meanwhile, a 6-bp deletion, namely c. 262+31_262+36delTCTGAC, was
      found in the intron of buffalo INHA gene. For this deletion, wild types (+/+)
      account for main part in river buffalo while mutant types (-/-) are predominant
      in swamp buffalo. This deletion was not found in gayal, yak and cattle, though
      these all have another deletion in the intron of INHA, c. 262+78_262+79delTG. The
      results of sequence alignment showed that the substitutions c. 43A and c. 67G in
      exon 1 of INHA are specific to buffalo, whereas the substitutions c. 173A and c.
      255G are exclusive to gayal, yak and cattle, and c. 24C, c. 47G, c. 174T and c.
      206T are specific to goat. Furthermore, there are few differences among gayal,
      yak and cattle, but there relatively great differences between buffalo, goat and
      other bovine species regarding the sequences of INHA exon 1.

PMID- 22855449
TI  - [Progress on the degeneration mechanism of cave fishes' eyes].
AB  - Attempts to understand the degeneration of the eyes in cave fish has largely been
      explained by either various extents of gradual degeneration, ranging from partial
      to total loss, observed in various species or by acceleration of loss caused by
      dark environments. However, neither the theory of biological evolution developed
      by Charles Darwin nor the neutral theory of molecular evolution formulated by
      Kimura Motoo adequately explains these phenomena. Recent trends in utilizing
      multidisciplinary research, however, have yielded better results, helping reveal
      a more complex picture of the mechanisms of degeneration. Here, we summarize the
      current progress of the research via morphology and anatomy, development biology,
      animal behavior science and molecular genetics, and offer some perspectives on
      the ongoing research into the development and degeneration of eyes in cave fish.

PMID- 22855450
TI  - [Research on MicroRNAs in pluripotent stem cells].
AB  - MicroRNAs (miRNAs) are a newly identified class of small regulatory non-coding
      endogenous RNAs that take part in a series of important processes by regulating
      gene expression. Recent studies have provided evidence that miRNAs may be
      involved in nearly all biological and metabolic processes, especially influencing
      self-renewal and differentiation of embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs). In this review, we briefly summarize the
      biological characteristics of miRNAs, the detection technologies, and the role of
      miRNAs regulation in ESCs and iPSCs to frame a discussion on the future prospects
      of miRNA research.

PMID- 22855451
TI  - [The mechanisms of weight-cutting effect and bioactive components in Pu-erh tea].
AB  - Originally grown and produced in southern of Yunnan, China, Pu-erh tea has a long
      history and carries rich cultural connotations. Consumption of Pu-erh has been
      thought to possess numerous health benefits including weight-loss, lowering of
      blood glucose levels, and preventing cardiovascular diseases. Research on humans,
      rodents, and cell lines have each confirmed that Pu-erh tea indeed displays
      weight-loss and blood lipid lowering effects. The main bioactive components, such
      as theabrownin (TB), polysaccharides, polyphenols, and statins, may down-regulate
      the biosynthesis of fat and up-regulate the oxidation of fat to cut weight and
      reduce the content of lipids in blood. Here, we summarize current progress on
      understanding the mechanisms and bioactive components of Pu-erh's weight-cutting
      effects as well as highlighting current weaknesses in the field in order to
      suggest possible solutions for future research on Pu-erh tea.

PMID- 22855452
TI  - Genetic diversity and differentiation of masu salmon (Oncorhynchus masou masou)
      between and within cultured populations inferred from microsatellite DNA
      analysis.
AB  - Masu salmon, Oncorhynchus masou masou, is one of the most valuable fishery
      species that has been introduced to China, though to date no studies on the
      genetic diversity and genetic relationship among hatchery populations has been
      performed with molecular markers. We undertook such a study and sampled 120
      individuals from three hatchery stocks and analyzed 20 microsatellite loci. All
      loci were polymorphic and a total of 91 alleles were detected. A relatively low
      level of genetic diversity was revealed with effective number of allele of
      3.1094, 3.3299 and 3.1894 and expected heterozygosity of 0.6600, 0.6648 and
      0.6638 in the three stocks, respectively. Deviations from Hardy-Weinberg
      equilibrium were found due to heterozygote deficit. Accordingly, evidence of
      genetic bottlenecks were found in the three stocks. An individual assignment test
      demonstrated that 85% of individuals were correctly assigned into their original
      stocks. Pairwise Fst revealed that significant differentiation occurred between
      these three stocks. The results of the study indicated that disequilibrium of
      genetic structure and differentiation has occurred in all three stocks. This
      information collectively provides a basis for measures to avoid of loss of
      genetic diversity and introgression in Chinese aquaculture.

PMID- 22855453
TI  - Molecular cloning and expression analysis of FTZ-F1 in the GIFT tilapia,
      Oreochromis niloticus.
AB  - The FTZ-F1 genes encode orphan receptors of the nuclear receptor superfamily and
      in mammals have been found to play important roles in the proper development of
      the adrenal-gonadal axis and sex-determination. We isolated the homologue of FTZ
      F1 in genetically improved farmed tilapia (gfFTZ-F1). The full-length cDNA was
      isolated from the ovary, which included an open reading frame encoding a
      predicted protein of 486 amino acids. Sequence, tissue distribution and
      phylogenic analysis of the FTZ-F1 showed that the gfFTZ-F1 belonged to SF-1/Ad4BP
      group and that gfFTZ-F1 transcripts were only expressed in the gonads and kidney
      but not in other tissues. Likewise our data suggests that the gfFTZ-F1 gene may
      share similar functions with other fish and mammalian counterparts, though
      further study is needed to make any definitive conclusions.

PMID- 22855454
TI  - Preliminary analysis of the mitochondrial genome evolutionary pattern in
      primates.
AB  - Since the birth of molecular evolutionary analysis, primates have been a central
      focus of study and mitochondrial DNA is well suited to these endeavors because of
      its unique features. Surprisingly, to date no comprehensive evaluation of the
      nucleotide substitution patterns has been conducted on the mitochondrial genome
      of primates. Here, we analyzed the evolutionary patterns and evaluated selection
      and recombination in the mitochondrial genomes of 44 Primates species downloaded
      from GenBank. The results revealed that a strong rate heterogeneity occurred
      among sites and genes in all comparisons. Likewise, an obvious decline in primate
      nucleotide diversity was noted in the subunit rRNAs and tRNAs as compared to the
      protein-coding genes. Within 13 protein-coding genes, the pattern of
      nonsynonymous divergence was similar to that of overall nucleotide divergence,
      while synonymous changes differed only for individual genes, indicating that the
      rate heterogeneity may result from the rate of change at nonsynonymous sites.
      Codon usage analysis revealed that there was intermediate codon usage bias in
      primate protein-coding genes, and supported the idea that GC mutation pressure
      might determine codon usage and that positive selection is not the driving force
      for the codon usage bias. Neutrality tests using site-specific positive selection
      from a Bayesian framework indicated no sites were under positive selection for
      any gene, consistent with near neutrality. Recombination tests based on the
      pairwise homoplasy test statistic supported complete linkage even for much older
      divergent primate species. Thus, with the exception of rate heterogeneity among
      mitochondrial genes, evaluating the validity assumed complete linkage and
      selective neutrality in primates prior to phylogenetic or phylogeographic
      analysis seems unnecessary.

PMID- 22855455
TI  - Description of a new record species of Heterodera from China (Tylenchida,
      Heteroderidae).
AB  - A new record species Heterodera ripae was found in the rhizosphere soil of nettle
      (Urtica sp.) on the bank of the Mangniu River in Shenyang City, Liaoning
      Province, China. The new record species can be characterized by vulval cone
      bifenestrate with circular or subcircular semifenestrae, vulval slit length
      averaging 34.2 MUm, vulval bridge mostly broad, underbridge weak, bullae absent;
      the second-stage larvae stylet knobs rather wide and slightly projecting
      anteriorly, tail length averaging 43.7 MUm and hyaline region length averaging
      22.3 MUm.

PMID- 22855456
TI  - The internal vertebral venous plexus.

PMID- 22855457
TI  - Ligand-accelerated activation of strong C-H bonds of alkanes by a
      (salen)ruthenium(VI)-nitrido complex.
AB  - Kinetic and mechanistic studies on the intermolecular activation of strong C-H
      bonds of alkanes by a (salen)ruthenium(VI) nitride were performed. The initial,
      rate-limiting step, the hydrogen atom transfer (HAT) from the alkane to Ru(VI)=N,
      generates Ru(V)=NH and RC.HCH(2)R. The following steps involve N-rebound and
      desaturation.

PMID- 22855458
TI  - Two drawings by Franz Batke in Gray's Anatomy.

PMID- 22855459
TI  - beta-Amyloid: enemy or remedy?

PMID- 22855460
TI  - Anti-CD25 immunotherapy: regulating the regulators.

PMID- 22855461
TI  - Drug screening for ALS using patient-specific induced pluripotent stem cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the
      motor neurons degenerate. The discovery of new drugs for treating ALS has been
      hampered by a lack of access to motor neurons from ALS patients and appropriate
      disease models. We generate motor neurons from induced pluripotent stem cells
      (iPSCs) from familial ALS patients, who carry mutations in Tar DNA binding
      protein-43 (TDP-43). ALS patient-specific iPSC-derived motor neurons formed
      cytosolic aggregates similar to those seen in postmortem tissue from ALS patients
      and exhibited shorter neurites as seen in a zebrafish model of ALS. The ALS motor
      neurons were characterized by increased mutant TDP-43 protein in a detergent
      insoluble form bound to a spliceosomal factor SNRPB2. Expression array analyses
      detected small increases in the expression of genes involved in RNA metabolism
      and decreases in the expression of genes encoding cytoskeletal proteins. We
      examined four chemical compounds and found that a histone acetyltransferase
      inhibitor called anacardic acid rescued the abnormal ALS motor neuron phenotype.
      These findings suggest that motor neurons generated from ALS patient-derived
      iPSCs may provide a useful tool for elucidating ALS disease pathogenesis and for
      screening drug candidates.

PMID- 22855462
TI  - Reversal of paralysis and reduced inflammation from peripheral administration of
      beta-amyloid in TH1 and TH17 versions of experimental autoimmune
      encephalomyelitis.
AB  - beta-Amyloid 42 (Abeta42) and beta-amyloid 40 (Abeta40), major components of
      senile plaque deposits in Alzheimer's disease, are considered neurotoxic and
      proinflammatory. In multiple sclerosis, Abeta42 is up-regulated in brain lesions
      and damaged axons. We found, unexpectedly, that treatment with either Abeta42 or
      Abeta40 peptides reduced motor paralysis and brain inflammation in four different
      models of experimental autoimmune encephalomyelitis (EAE) with attenuation of
      motor paralysis, reduction of inflammatory lesions in the central nervous system
      (CNS), and suppression of lymphocyte activation. Abeta42 and Abeta40 treatments
      were effective in reducing ongoing paralysis induced with adoptive transfer of
      either autoreactive T helper 1 (T(H)1) or T(H)17 cells. High-dimensional 14
      parameter flow cytometry of peripheral immune cell populations after in vivo
      Abeta42 and Abeta40 treatment revealed substantial modulations in the percentage
      of lymphoid and myeloid subsets during EAE. Major proinflammatory cytokines and
      chemokines were reduced in the blood after Abeta peptide treatment. Protection
      conferred by Abeta treatment did not require its delivery to the brain: Adoptive
      transfer with lymphocytes from donors treated with Abeta42 attenuated EAE in wild
      type recipient mice, and Abeta deposition in the brain was not detected in
      treated EAE mice by immunohistochemical analysis. In contrast to the improvement
      in EAE with Abeta treatment, EAE was worse in mice with genetic deletion of the
      amyloid precursor protein. Therefore, in the absence of Abeta, there is
      exacerbated clinical EAE disease progression. Because Abeta42 and Abeta40
      ameliorate experimental autoimmune inflammation targeting the CNS, we might now
      consider its potential anti-inflammatory role in other neuropathological
      conditions.

PMID- 22855463
TI  - Inhibition of LTi cell development by CD25 blockade is associated with decreased
      intrathecal inflammation in multiple sclerosis.
AB  - Genetic polymorphisms in the interleukin-2 receptor alpha (IL-2Ralpha) chain
      (CD25) locus are associated with several human autoimmune diseases, including
      multiple sclerosis (MS). Blockade of CD25 by the humanized monoclonal antibody
      daclizumab decreases MS-associated inflammation but has surprisingly limited
      direct inhibitory effects on activated T cells. The present study describes
      unexpected effects of daclizumab therapy on innate lymphoid cells (ILCs). The
      number of circulating retinoic acid receptor-related orphan receptor gammat
      positive ILCs, which include lymphoid tissue inducer (LTi) cells, was found to be
      elevated in untreated MS patients compared to healthy subjects. Daclizumab
      therapy not only decreased numbers of ILCs but also modified their phenotype away
      from LTi cells and toward a natural killer (NK) cell lineage. Mechanistic studies
      indicated that daclizumab inhibited differentiation of LTi cells from CD34+
      hematopoietic progenitor cells or c-kit+ ILCs indirectly, steering their
      differentiation toward immunoregulatory CD56(bright) NK cells through enhanced
      intermediate-affinity IL-2 signaling. Because adult LTi cells may retain lymphoid
      tissue-inducing capacity or stimulate adaptive immune responses, we indirectly
      measured intrathecal inflammation in daclizumab-treated MS patients by
      quantifying the cerebrospinal fluid chemokine (C-X-C motif) ligand 13 and
      immunoglobulin G index. Both of these inflammatory biomarkers were inhibited by
      daclizumab treatment. Our study indicates that ILCs are involved in the
      regulation of adaptive immune responses, and their role in human autoimmunity
      should be investigated further, including their potential as therapeutic targets.

PMID- 22855464
TI  - Tough at the top: must end-expiratory lung volume make way for end-inspiratory
      lung volume?

PMID- 22855465
TI  - The hidden costs of environmental contamination.

PMID- 22855466
TI  - Apoptotic cell clearance and fibrotic lung disease.

PMID- 22855467
TI  - Tidal volume, recruitment and compliance in HFOV: same principles, different
      frequency.

PMID- 22855468
TI  - Clinical COPD phenotypes identified by cluster analysis: validation with
      mortality.

PMID- 22855469
TI  - A new point of care cotinine test for saliva to identify and monitor smoking
      habit.

PMID- 22855471
TI  - Availability of anti-tuberculosis drugs in Europe.

PMID- 22855470
TI  - Drug-resistant tuberculosis among foreign-born persons in Italy.

PMID- 22855472
TI  - Continuous positive airway pressure delivered by oronasal mask may not be
      effective for obstructive sleep apnoea.

PMID- 22855473
TI  - Combined pulmonary fibrosis and emphysema associated with microscopic
      polyangiitis.

PMID- 22855474
TI  - Patient involvement in agenda setting for respiratory research in The
      Netherlands.

PMID- 22855475
TI  - Viral infections trigger exacerbations of cystic fibrosis in adults and children.

PMID- 22855476
TI  - Sleep apnoea and post-stroke vascular events: is it only due to poor continuous
      positive airway pressure use?

PMID- 22855479
TI  - Virome analysis for identification of novel mammalian viruses in bat species from
      Chinese provinces.
AB  - Bats are natural hosts for a large variety of zoonotic viruses. This study aimed
      to describe the range of bat viromes, including viruses from mammals, insects,
      fungi, plants, and phages, in 11 insectivorous bat species (216 bats in total)
      common in six provinces of China. To analyze viromes, we used sequence
      independent PCR amplification and next-generation sequencing technology (Solexa
      Genome Analyzer II; Illumina). The viromes were identified by sequence similarity
      comparisons to known viruses. The mammalian viruses included those of the
      Adenoviridae, Herpesviridae, Papillomaviridae, Retroviridae, Circoviridae,
      Rhabdoviridae, Astroviridae, Flaviridae, Coronaviridae, Picornaviridae, and
      Parvovirinae; insect viruses included those of the Baculoviridae, Iflaviridae,
      Dicistroviridae, Tetraviridae, and Densovirinae; fungal viruses included those of
      the Chrysoviridae, Hypoviridae, Partitiviridae, and Totiviridae; and phages
      included those of the Caudovirales, Inoviridae, and Microviridae and unclassified
      phages. In addition to the viruses and phages associated with the insects,
      plants, and bacterial flora related to the diet and habitation of bats, we
      identified the complete or partial genome sequences of 13 novel mammalian
      viruses. These included herpesviruses, papillomaviruses, a circovirus, a
      bocavirus, picornaviruses, a pestivirus, and a foamy virus. Pairwise alignments
      and phylogenetic analyses indicated that these novel viruses showed little
      genetic similarity with previously reported viruses. This study also revealed a
      high prevalence and diversity of bat astroviruses and coronaviruses in some
      provinces. These findings have expanded our understanding of the viromes of bats
      in China and hinted at the presence of a large variety of unknown mammalian
      viruses in many common bat species of mainland China.

PMID- 22855480
TI  - Human rotavirus-specific IgM Memory B cells have differential cloning
      efficiencies and switch capacities and play a role in antiviral immunity in vivo.
AB  - Protective immunity to rotavirus (RV) is primarily mediated by antibodies
      produced by RV-specific memory B cells (RV-mBc). Of note, most of these cells
      express IgM, but the function of this subset is poorly understood. Here, using
      limiting dilution assays of highly sort-purified human IgM(+) mBc, we found that
      62% and 21% of total (non-antigen-specific) IgM(+) and RV-IgM(+) mBc,
      respectively, switched in vitro to IgG production after polyclonal stimulation.
      Moreover, in these assays, the median cloning efficiencies of total IgM(+) (17%)
      and RV-IgM(+) (7%) mBc were lower than those of the corresponding switched
      (IgG(+) IgA(+)) total (34%) and RV-mBc (17%), leading to an underestimate of
      their actual frequency. In order to evaluate the in vivo role of IgM(+) RV-mBc in
      antiviral immunity, NOD/Shi-scid interleukin-2 receptor-deficient (IL
      2Rgamma(null)) immunodeficient mice were adoptively transferred highly purified
      human IgM(+) mBc and infected with virulent murine rotavirus. These mice
      developed high titers of serum human RV-IgM and IgG and had significantly lower
      levels than control mice of both antigenemia and viremia. Finally, we determined
      that human RV-IgM(+) mBc are phenotypically diverse and significantly enriched in
      the IgM(hi) IgD(low) subset. Thus, RV-IgM(+) mBc are heterogeneous, occur more
      frequently than estimated by traditional limiting dilution analysis, have the
      capacity to switch Ig class in vitro as well as in vivo, and can mediate systemic
      antiviral immunity.

PMID- 22855481
TI  - Spatiotemporal dynamics of adenovirus membrane rupture and endosomal escape.
AB  - A key step in adenovirus cell entry is viral penetration of cellular membranes to
      gain access to the cytoplasm and deliver the genome to the nucleus. Yet little is
      known about this important event in the adenoviral life cycle. Using the
      cytosolic protein galectin-3 (gal3) as a marker of membrane rupture with both
      live- and fixed-cell imaging, we demonstrate that in the majority of instances,
      exposure of pVI and recruitment of gal3 to ruptured membranes occur early at or
      near the cell surface and occur minimally in EEA-1-positive (EEA-1(+)) early
      endosomes or LAMP-1(+) late endosomes/lysosomes. Live-cell imaging of Ad5 egress
      from gal3(+) endosomes occurs most frequently from perinuclear locations. While
      the Ad5 capsid is observed escaping from gal3(+) endosomes, pVI appears to remain
      associated with the gal3(+) ruptured endosomes. Thus, Ad5 membrane rupture and
      endosomal escape appear to be both spatially and temporally distinct events.

PMID- 22855482
TI  - YB-1 functions as a porter to lead influenza virus ribonucleoprotein complexes to
      microtubules.
AB  - De novo-synthesized RNAs are under the regulation of multiple posttranscriptional
      processes by a variety of RNA-binding proteins. The influenza virus genome
      consists of single-stranded RNAs and exists as viral ribonucleoprotein (vRNP)
      complexes. After the replication of vRNP in the nucleus, it is exported to the
      cytoplasm and then reaches the budding site beneath the cell surface in a process
      mediated by Rab11a-positive recycling endosomes along microtubules. However, the
      regulatory mechanisms of the postreplicational processes of vRNP are largely
      unknown. Here we identified, as a novel vRNP-interacting protein, Y-box-binding
      protein 1 (YB-1), a cellular protein that is involved in regulation of cellular
      transcription and translation. YB-1 translocated to the nucleus from the
      cytoplasm and accumulated in PML nuclear bodies in response to influenza virus
      infection. vRNP assembled into the exporting complexes with YB-1 at PML nuclear
      bodies. After nuclear export, using YB-1 knockdown cells and in vitro
      reconstituted systems, YB-1 was shown to be required for the interaction of vRNP
      exported from the nucleus with microtubules around the microtubule-organizing
      center (MTOC), where Rab11a-positive recycling endosomes were located. Further,
      we also found that YB-1 overexpression stimulates the production of progeny
      virions in an Rab11a-dependent manner. Taking these findings together, we propose
      that YB-1 is a porter that leads vRNP to microtubules from the nucleus and puts
      it into the vesicular trafficking system.

PMID- 22855483
TI  - Cryo-electron tomography of rubella virus.
AB  - Rubella virus is the only member of the Rubivirus genus within the Togaviridae
      family and is the causative agent of the childhood disease known as rubella or
      German measles. Here, we report the use of cryo-electron tomography to examine
      the three-dimensional structure of rubella virions and compare their structure to
      that of Ross River virus, a togavirus belonging the genus Alphavirus. The
      ectodomains of the rubella virus glycoproteins, E1 and E2, are shown to be
      organized into extended rows of density, separated by 9 nm on the viral surface.
      We also show that the rubella virus nucleocapsid structure often forms a roughly
      spherical shell which lacks high density at its center. While many rubella
      virions are approximately spherical and have dimensions similar to that of the
      icosahedral Ross River virus, the present results indicate that rubella exhibits
      a large degree of pleomorphy. In addition, we used rotation function calculations
      and other analyses to show that approximately spherical rubella virions lack the
      icosahedral organization which characterizes Ross River and other alphaviruses.
      The present results indicate that the assembly mechanism of rubella virus, which
      has previously been shown to differ from that of the alphavirus assembly pathway,
      leads to an organization of the rubella virus structural proteins that is
      different from that of alphaviruses.

PMID- 22855484
TI  - Hepatitis C virus (HCV) induces formation of stress granules whose proteins
      regulate HCV RNA replication and virus assembly and egress.
AB  - Stress granules (SGs) are cytoplasmic structures that are induced in response to
      environmental stress, including viral infections. Here we report that hepatitis C
      virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)
      dependent manner. Moreover, we show an inverse correlation between the presence
      of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and
      USP18, in HCV-infected cells despite high-level expression of the corresponding
      MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is
      inhibited in stress granule-containing HCV-infected cells. Finally, in short
      hairpin RNA (shRNA) knockdown experiments, we found that the stress granule
      proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein
      (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for
      efficient HCV RNA and protein accumulation at early time points in the infection
      and that G3BP1 and TIA-1 are required for intracellular and extracellular
      infectious virus production late in the infection, suggesting that they are
      required for virus assembly. In contrast, TIAR downregulation decreases
      extracellular infectious virus titers with little effect on intracellular RNA
      content or infectivity late in the infection, suggesting that it is required for
      infectious particle release. Collectively, these results illustrate that HCV
      exploits the stress granule machinery at least two ways: by inducing the
      formation of SGs by triggering PKR phosphorylation, thereby downregulating the
      translation of antiviral interferon-stimulated genes, and by co-opting SG
      proteins for its replication, assembly, and egress.

PMID- 22855485
TI  - Acute diarrhea in West African children: diverse enteric viruses and a novel
      parvovirus genus.
AB  - Parvoviruses cause a variety of mild to severe symptoms or asymptomatic
      infections in humans and animals. During a viral metagenomic analysis of feces
      from children with acute diarrhea in Burkina Faso, we identified in decreasing
      prevalence nucleic acids from anelloviruses, dependoviruses, sapoviruses,
      enteroviruses, bocaviruses, noroviruses, adenoviruses, parechoviruses,
      rotaviruses, cosavirus, astroviruses, and hepatitis B virus. Sequences from a
      highly divergent parvovirus, provisionally called bufavirus, were also detected
      whose NS1 and VP1 proteins showed <39% and <31% identities to those of previously
      known parvoviruses. Four percent of the fecal samples were PCR positive for this
      new parvovirus, including a related bufavirus species showing only 72% identity
      in VP1. The high degree of genetic divergence of these related genomes from those
      of other parvoviruses indicates the presence of a proposed new Parvoviridae genus
      containing at least two species. Studies of the tropism and pathogenicity of
      these novel parvoviruses will be facilitated by the availability of their genome
      sequences.

PMID- 22855486
TI  - A mutation deleting sequences encoding the amino terminus of human
      cytomegalovirus UL84 impairs interaction with UL44 and capsid localization.
AB  - Protein-protein interactions are required for many biological functions. Previous
      work has demonstrated an interaction between the human cytomegalovirus DNA
      polymerase subunit UL44 and the viral replication factor UL84. In this study,
      glutathione S-transferase pulldown assays indicated that residues 1 to 68 of UL84
      are both necessary and sufficient for efficient interaction of UL84 with UL44 in
      vitro. We created a mutant virus in which sequences encoding these residues were
      deleted. This mutant displayed decreased virus replication compared to wild-type
      virus. Immunoprecipitation assays showed that the mutation decreased but did not
      abrogate association of UL84 with UL44 in infected cell lysate, suggesting that
      the association in the infected cell can involve other protein-protein
      interactions. Further immunoprecipitation assays indicated that IRS1, TRS1, and
      nucleolin are candidates for such interactions in infected cells. Quantitative
      real-time PCR analysis of viral DNA indicated that the absence of the UL84 amino
      terminus does not notably affect viral DNA synthesis. Western blotting
      experiments and pulse labeling of infected cells with [(35)S]methionine
      demonstrated a rather modest downregulation of levels of multiple proteins and
      particularly decreased levels of the minor capsid protein UL85. Electron
      microscopy demonstrated that viral capsids assemble but are mislocalized in
      nuclei of cells infected with the mutant virus, with fewer cytoplasmic capsids
      detected. In sum, deletion of the sequences encoding the amino terminus of UL84
      affects interaction with UL44 and virus replication unexpectedly, not viral DNA
      synthesis. Mislocalization of viral capsids in infected cell nuclei likely
      contributes to the observed decrease in virus replication.

PMID- 22855487
TI  - Identification of transmembrane protein 134 as a novel LMP1-binding protein by
      using bimolecular fluorescence complementation and an enhanced retroviral
      mutagen.
AB  - Latent membrane protein 1 (LMP1) of Epstein-Barr virus induces constitutive
      signaling in infected cells. LMP1 signaling requires oligomerization of LMP1 via
      its transmembrane domain, localization to lipid rafts in the membrane, and
      association of the LMP1 cytoplasmic domain to adaptor proteins, such as the tumor
      necrosis factor receptor-associated factors (TRAFs). Protein complementation is a
      novel technique to examine protein-protein interaction through the assembly of
      functional fluorescent proteins or enzymes from inactive fragments. A previous
      study in our lab demonstrated the use of bimolecular fluorescence complementation
      (BiFC) to study the assembly of the LMP1 signaling complexes within the plasma
      membrane of mammalian cells. In the present study, LMP1 was used as bait in a
      genome-wide BiFC screen with an enhanced retroviral mutagen to identify new LMP1
      binding proteins. Our screen identified a novel LMP1-binding protein,
      transmembrane protein 134 (Tmem134). Tmem134 is a candidate oncogene that is
      amplified in breast cancer cell lines. Binding, colocalization, and
      cofractionation between LMP1 and Tmem134 were confirmed. Finally, Tmem134
      affected LMP1-induced NF-kappaB induction. Together, these data suggest that BiFC
      is a unique and novel platform to identify proteins recruited to the LMP1
      signaling complex.

PMID- 22855488
TI  - Severe acute respiratory syndrome coronavirus nsp1 facilitates efficient
      propagation in cells through a specific translational shutoff of host mRNA.
AB  - Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus
      containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a
      set of common 5' and 3' untranslated regions (UTR) are synthesized from the
      incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1
      protein causes a severe translational shutoff by binding to the 40S ribosomal
      subunits. The nsp1-40S ribosome complex further induces an endonucleolytic
      cleavage near the 5'UTR of host mRNA. However, the mechanism by which SCoV viral
      proteins are efficiently produced in infected cells in which host protein
      synthesis is impaired by nsp1 is unknown. In this study, we investigated the role
      of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities
      were significantly suppressed in cells expressing nsp1 together with the mRNA
      carrying a luciferase gene, while nsp1 failed to suppress luciferase activities
      of the mRNA flanked by the 5'UTR of SCoV. An RNA-protein binding assay and RNA
      decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5'UTR of SCoV
      RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1.
      Furthermore, experiments using an SCoV replicon system showed that the specific
      interaction enhanced the SCoV replication. The specific interaction of nsp1 with
      SL1 is an important strategy to facilitate efficient viral gene expression in
      infected cells, in which nsp1 suppresses host gene expression. Our data indicate
      a novel mechanism of viral gene expression control by nsp1 and give new insight
      into understanding the pathogenesis of SARS.

PMID- 22855489
TI  - Membrane interaction of the portal protein gp20 of bacteriophage T4.
AB  - Assembly of the bacteriophage T4 head structure occurs at the cytoplasmic face of
      the inner membrane of Escherichia coli with the formation of proheads. The
      proheads contain an internal scaffolding core that determines the size and the
      structure of the capsid. In a mutant where the major shell protein gp23 was
      compromised, core structures without a shell had been detected. Such core
      structures were also found in the mutant T4am20am23. Since the mutation in gene
      20 is at the N terminus of gp20, it was assumed that these core structures
      assemble in the absence of gp20. However, sequencing showed that the mutation
      introduces a new ribosome binding site that leads to a restart at codon 15.
      Although the mutant protein gp20s lacks the very N-terminal sequence, we found
      that it still binds to the membrane of the host cell and can initiate prohead
      assembly. This explains its activity to allow the assembly of core structures and
      proheads at the membrane surface. With a cross-linking approach, we show here
      that gp20 and gp20s are escorted by the chaperones DnaK, trigger factor, and
      GroEL and dock on the membrane at the membrane protein YidC.

PMID- 22855490
TI  - Analysis of Epstein-Barr virus-regulated host gene expression changes through
      primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1
      mediated NF-kappaB activation.
AB  - Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that dramatically
      reorganizes host gene expression to immortalize primary B cells. In this study,
      we analyzed EBV-regulated host gene expression changes following primary B-cell
      infection, both during initial proliferation and through transformation into
      lymphoblastoid cell lines (LCLs). While most EBV-regulated mRNAs were changed
      during the transition from resting, uninfected B cells through initial B-cell
      proliferation, a substantial number of mRNAs changed uniquely from early
      proliferation through LCL outgrowth. We identified constitutively and dynamically
      EBV-regulated biological processes, protein classes, and targets of specific
      transcription factors. Early after infection, genes associated with
      proliferation, stress responses, and the p53 pathway were highly enriched.
      However, the transition from early to long-term outgrowth was characterized by
      genes involved in the inhibition of apoptosis, the actin cytoskeleton, and NF
      kappaB activity. It was previously thought that the major viral protein
      responsible for NF-kappaB activation, latent membrane protein 1 (LMP1), is
      expressed within 2 days after infection. Our data indicate that while this is
      true, LCL-level LMP1 expression and NF-kappaB activity are not evident until 3
      weeks after primary B-cell infection. Furthermore, heterologous NF-kappaB
      activation during the first week after infection increased the transformation
      efficiency, while early NF-kappaB inhibition had no effect on transformation.
      Rather, inhibition of NF-kappaB was not toxic to EBV-infected cells until LMP1
      levels and NF-kappaB activity were high. These data collectively highlight the
      dynamic nature of EBV-regulated host gene expression and support the notion that
      early EBV-infected proliferating B cells have a fundamentally distinct growth and
      survival phenotype from that of LCLs.

PMID- 22855491
TI  - Structural basis for the recognition of Lewis antigens by genogroup I norovirus.
AB  - Noroviruses (NoVs) bind to histo-blood group antigens, namely, ABH antigens and
      Lewis antigens. We previously showed the NoVs GI/2, GI/3, GI/4, and GI/8 were
      able to strongly bind to Lewis a (Le(a)) antigen, which is expressed by
      individuals who are nonsecretors. In this study, to investigate how Lewis
      antigens interact with GI NoV virion protein 1 (VP1), we determined the crystal
      structures of the P domain of the VP1 protein from the Funabashi 258 (FUV258)
      strain (GI/2) in complexes with Le(a), Le(b), H type 1, or A type 1 antigens. The
      structures were compared with those of the NV/68 strain (GI/1), which does not
      bind to the Le(a) antigen. The four loop structures, loop P, loop S, loop A, and
      loop B, continuously deviated by more than 2 A in length between the Calpha atoms
      of the corresponding residues of the FUV258 and NV/68 P domains. The most
      pronounced differences between the two VP1 proteins were observed in the
      structures of loop P. In the FUV258 P domain, loop P protruded toward the next
      protomer, forming a Le(a) antigen-binding site. The Gln389 residue make a
      significant contribution to the binding of the Le(a) antigen through the
      stabilization of loop P as well as through direct interactions with the alpha4
      fucosyl residue (alpha4Fuc) of the Le(a) antigen. Mutation of the Gln389 residue
      dramatically affected the degree of binding of the Lewis antigens. Collectively,
      these results suggest that loop P and the amino acid residue at position 389
      affect Lewis antigen binding.

PMID- 22855492
TI  - Cross-species transmission in the speciation of the currently known murinae
      associated hantaviruses.
AB  - To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried by
      Niviventer confucianus and other Murinae-associated hantaviruses, genome
      sequences of novel variants of DBSV were recovered from Niviventer rats trapped
      in the mountainous areas of Wenzhou, China. Genetic analyses show that all known
      genetic variants of DBSV, including the ones identified in this study, are
      distinct from other Murinae-associated hantaviruses. DBSV variants show
      geographic clustering and high intraspecies diversity. The data suggest that DBSV
      is a distinct species in the genus Hantavirus. Interestingly, DBSV shows the
      highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the
      sequences of the N, GPC, and L proteins, while N. confucianus is more closely
      related to Rattus norvegicus (the host of Seoul virus [SEOV]) than to Apodemus
      agrarius (the host of HTNV and Saaremaa virus [SAAV]). Further genetic analyses
      of all known Murinae-associated hantaviruses (both established and tentative
      species) show that many of them, including DBSV, may have originated from host
      switching. The estimation of evolutionary rates and divergence time supports the
      role of cross-species transmission in the evolution of Murinae-associated
      hantaviruses. The detection of positive selection suggests that genetic drift may
      contribute to the speciation of Murinae-associated hantaviruses and that
      adaptation has a role as well.

PMID- 22855493
TI  - Persistent infection of thymic epithelial cells with coxsackievirus B4 results in
      decreased expression of type 2 insulin-like growth factor.
AB  - It has been hypothesized that a disturbance of central self-tolerance to islet
      beta cells may play a role in the enteroviral pathogenesis of type 1 diabetes.
      Whether enteroviruses can induce an impaired expression of beta-cell self
      antigens in thymic epithelial cells has been investigated in a murine thymic
      epithelial (MTE) cell line. This cell line was permissive to the diabetogenic
      group B4 coxsackievirus (CV-B4) strain CV-B4 E2 and spontaneously expressed type
      2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin
      family. In this model, a persistent replication of CV-B4 E2 was obtained, as
      attested to by the prolonged detection of intracellular positive- and negative
      strand viral RNA by reverse transcription-PCR (RT-PCR) and capsid protein VP1 by
      immunofluorescent staining and by the release of infectious particles in culture
      supernatants. The chronic stage of the infection was characterized by a low
      proportion of VP1-positive cells (1 to 2%), whereas many cells harbored
      enteroviral RNA, as displayed by RT-PCR without extraction applied directly to a
      few cells. Igf2 mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2
      infected MTE cell cultures compared with mock-infected cultures, whereas
      housekeeping and interleukin-6 (Il6) gene expression was maintained and Igf1 mRNA
      was decreased, but to a lower extent. Inoculation of CV-B3, CV-B4 JVB, or
      echovirus 1 resulted in a low level of IGF-2 in culture supernatants as well,
      whereas herpes simplex virus 1 stimulated the production of the protein. Thus, a
      persistent infection of a thymic epithelial cell line with enteroviruses like CV
      B4 E2 can result in a disturbed production of IGF-2, a protein involved in
      central self-tolerance toward islet beta cells.

PMID- 22855494
TI  - Increased viral loads and exacerbated innate host responses in aged macaques
      infected with the 2009 pandemic H1N1 influenza A virus.
AB  - In contrast to seasonal influenza virus infections, which typically cause
      significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused
      severe infection in young adults. This phenomenon was attributed to the presence
      of cross-protective antibodies acquired by older individuals during previous
      exposures to H1N1 viruses. However, this hypothesis could not be empirically
      tested. To address this question, we compared viral replication and the
      development of the immune response in naive young adult and aged female rhesus
      macaques infected with A/California/04/2009 H1N1 (CA04) virus. We show higher
      viral loads in the bronchoalveolar lavage (BAL) fluid and nasal and ocular swabs
      in aged animals, suggesting increased viral replication in both the lower and
      upper respiratory tracts. T cell proliferation was higher in the BAL fluid but
      delayed and reduced in peripheral blood in aged animals. This delay in
      proliferation correlated with a reduced frequency of effector CD4 T cells in old
      animals. Aged animals also mobilized inflammatory cytokines to higher levels in
      the BAL fluid. Finally, we compared changes in gene expression using microarray
      analysis of BAL fluid samples. Our analyses revealed that the largest difference
      in host response between aged and young adult animals was detected at day 4
      postinfection, with a significantly higher induction of genes associated with
      inflammation and the innate immune response in aged animals. Overall, our data
      suggest that, in the absence of preexisting antibodies, CA04 infection in aged
      macaques is associated with changes in innate and adaptive immune responses that
      were shown to correlate with increased disease severity in other respiratory
      disease models.

PMID- 22855495
TI  - Symmetry-related clustering of positive charges is a common mechanism for heparan
      sulfate binding in enteroviruses.
AB  - Coxsackievirus A9 (CAV9), a member of the Picornaviridae family, uses an RGD
      motif in the VP1 capsid protein to bind to integrin alphavbeta6 during cell
      entry. Here we report that two CAV9 isolates can bind to the heparan
      sulfate/heparin class of proteoglycans (HSPG). Sequence analysis identified an
      arginine (R) at position 132 in VP1 in these two isolates, rather than a
      threonine (T) as seen in the nonbinding strains tested. We introduced a T132R
      substitution into the HSPG-nonbinding strain Griggs and recovered infectious
      virus capable of binding to immobilized heparin, unlike the parental Griggs
      strain. The known CAV9 structure was used to identify the location of VP1
      position 132, 5 copies of which were found to cluster around the 5-fold axis of
      symmetry, presumably producing a region of positive charge which can interact
      with the negatively charged HSPG. Analysis of several enteroviruses of the same
      species as CAV9, Human enterovirus B (HEV-B), identified examples from 5 types in
      which blocking of infection by heparin was coincident with an arginine (or
      another basic amino acid, lysine) at a position corresponding to 132 in VP1 in
      CAV9. Together, these data show that membrane-associated HSPG can serve as a
      (co)receptor for some CAV9 and other HEV-B strains and identify symmetry-related
      clustering of positive charges as one mechanism by which HSPG binding can be
      achieved. This is a potentially powerful mechanism by which a single amino acid
      change could generate novel receptor binding capabilities, underscoring the
      plasticity of host-cell interactions in enteroviruses.

PMID- 22855496
TI  - Large-scale spatial and temporal genetic diversity of feline calicivirus.
AB  - Feline calicivirus (FCV) is an important pathogen of domestic cats and a
      frequently used model of human caliciviruses. Here we use an epidemiologically
      rigorous sampling framework to describe for the first time the phylodynamics of a
      calicivirus at regional and national scales. A large number of FCV strains
      cocirculated in the United Kingdom at the national and community levels, with no
      strain comprising more than 5% and 14% of these populations, respectively. The
      majority of strains exhibited a relatively restricted geographical range, with
      only two strains (one field virus and one vaccine virus) spreading further than
      100 km. None of the field strains were identified outside the United Kingdom.
      Temporally, while some strains persisted locally for the majority of the study,
      others may have become locally extinct. Evolutionary analysis revealed a radial
      phylogeny with little bootstrap support for nodes above the strain level. In most
      cases, spatially and temporally diverse strains intermingled in the phylogeny.
      Together, these data suggest that current FCV evolution is not associated with
      selective competition among strains. Rather, the genetic and antigenic landscape
      in each geographical location is highly complex, with many strains cocirculating.
      These variants likely exist at the community level by a combination of de novo
      evolution and occasional gene flow from the wider national population. This
      complexity provides a benchmark, for the first time, against which vaccine cross
      protection at both local and national levels can be judged.

PMID- 22855497
TI  - Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the
      release efficiency and infectivity of HIV-1.
AB  - Human endogenous retroviruses (HERVs), which are remnants of ancestral
      retroviruses integrated into the human genome, are defective in viral
      replication. Because activation of HERV-K and coexpression of this virus with HIV
      1 have been observed during HIV-1 infection, it is conceivable that HERV-K could
      affect HIV-1 replication, either by competition or by cooperation, in cells
      expressing both viruses. In this study, we found that the release efficiency of
      HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition,
      we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON)
      Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON)
      Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of
      HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of
      virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late
      domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation
      deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear
      trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed
      to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane.
      Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required
      nucleocapsid (NC). These results provide evidence that HIV-1 Gag
      heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC
      RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1
      release efficiency but also HIV-1 infectivity in a myristylation- and NC
      dependent manner. Altogether, these results indicate that Gag proteins of
      endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase
      of HIV-1 replication.

PMID- 22855498
TI  - Hepatitis C virus envelope glycoprotein fitness defines virus population
      composition following transmission to a new host.
AB  - Genetic variability is a hallmark of RNA virus populations. However, transmission
      to a new host often results in a marked decrease in population diversity. This
      genetic bottlenecking is observed during hepatitis C virus (HCV) transmission and
      can arise via a selective sweep or through the founder effect. To model HCV
      transmission, we utilized chimeric SCID/Alb-uPA mice with transplanted human
      hepatocytes and infected them with a human serum HCV inoculum. E1E2 glycoprotein
      gene sequences in the donor inoculum and recipient mice were determined following
      single-genome amplification (SGA). In independent experiments, using mice with
      liver cells grafted from different sources, an E1E2 variant undetectable in the
      source inoculum was selected for during transmission. Bayesian coalescent
      analyses indicated that this variant arose in the inoculum pretransmission.
      Transmitted variants that established initial infection harbored key
      substitutions in E1E2 outside HVR1. Notably, all posttransmission E1E2s had lost
      a potential N-linked glycosylation site (PNGS) in E2. In lentiviral
      pseudoparticle assays, the major posttransmission E1E2 variant conferred an
      increased capacity for entry compared to the major variant present in the
      inoculum. Together, these data demonstrate that increased envelope glycoprotein
      fitness can drive selective outgrowth of minor variants posttransmission and that
      loss of a PNGS is integral to this improved phenotype. Mathematical modeling of
      the dynamics of competing HCV variants indicated that relatively modest
      differences in glycoprotein fitness can result in marked shifts in virus
      population composition. Overall, these data provide important insights into the
      dynamics and selection of HCV populations during transmission.

PMID- 22855499
TI  - Circumventing antivector immunity by using adenovirus-infected blood cells for
      repeated application of adenovirus-vectored vaccines: proof of concept in rhesus
      macaques.
AB  - Adenovirus has been extensively exploited as a vector platform for delivering
      vaccines. However, preexisting antiadenovirus immunity is the major stumbling
      block for application of adenovirus-vectored vaccines. In this study, we found
      that freshly isolated peripheral blood mononuclear cells (PBMCs), mostly CD14(+)
      cells, from adenovirus serotype 5 (Ad5)-seropositive primates (humans and rhesus
      macaques) can be efficiently infected with Ad5 in vitro. On the basis of this
      observation, a novel strategy based on adenoviral vector-infected PBMC (AVIP)
      immunization was explored to circumvent antivector immunity. Autologous infusion
      of Ad5-SIVgag-infected PBMCs elicited a strong Gag-specific cellular immune
      response but induced weaker Ad5-neutralizing antibody (NAb) in Ad5-seronegative
      macaques than in macaques intramuscularly injected with Ad5-SIVgag. Moreover, Ad5
      seropositive macaques receiving multiple AVIP immunizations with Ad5-SIVenv, Ad5
      SIVgag, and Ad5-SIVpol vaccines elicited escalated Env-, Gag-, and Pol-specific
      immune responses after each immunization that were significantly greater than
      those in macaques intramuscularly injected with these Ad5-SIV vaccines. After
      challenged intravenously with a highly pathogenic SIVmac239 virus, macaques
      receiving AVIP immunization demonstrated a significant reduction in viral load at
      both the peak time and set-point period compared with macaques without Ad5-SIV
      vaccines. Our study warranted further research and development of the AVIP
      immunization as a platform for repeated applications of adenovirus-vectored
      vaccines.

PMID- 22855500
TI  - Hepatitis C virus induces epidermal growth factor receptor activation via CD81
      binding for viral internalization and entry.
AB  - While epidermal growth factor receptor (EGFR) has been shown to be important in
      the entry process for multiple viruses, including hepatitis C virus (HCV), the
      molecular mechanisms by which EGFR facilitates HCV entry are not well understood.
      Using the infectious cell culture HCV model (HCVcc), we demonstrate that the
      binding of HCVcc particles to human hepatocyte cells induces EGFR activation that
      is dependent on interactions between HCV and CD81 but not claudin 1. EGFR
      activation can also be induced by antibody mediated cross-linking of CD81. In
      addition, EGFR ligands that enhance the kinetics of HCV entry induce EGFR
      internalization and colocalization with CD81. While EGFR kinase inhibitors
      inhibit HCV infection primarily by preventing EGFR endocytosis, antibodies that
      block EGFR ligand binding or inhibitors of EGFR downstream signaling have no
      effect on HCV entry. These data demonstrate that EGFR internalization is critical
      for HCV entry and identify a hitherto-unknown association between CD81 and EGFR.

PMID- 22855502
TI  - Focus issue: regulation of lymphocyte function.
AB  - During the month of July, Science Signaling has highlighted mechanisms by which
      lymphocytes of the innate and adaptive immune responses are regulated to promote
      effective immunity and prevent inappropriate and damaging responses. Research
      Articles and Perspectives in this series and the Archives focus on the mechanisms
      by which the functions of T cells, B cells, and natural killer cells are
      regulated and the therapeutic implications of understanding the regulation of
      these cells.

PMID- 22855501
TI  - Incoming influenza A virus evades early host recognition, while influenza B virus
      induces interferon expression directly upon entry.
AB  - The activation of the interferon (IFN) system, which is triggered largely by the
      recognition of viral nucleic acids, is one of the most important host defense
      reactions against viral infections. Although influenza A and B viruses, which
      both have segmented negative-strand RNA genomes, share major structural
      similarities, they have evolutionarily diverged, with total genetic
      incompatibility. Here we compare antiviral-inducing mechanisms during infections
      with type A and B influenza viruses in human dendritic cells. We observed that
      IFN responses are induced significantly faster in cells infected with influenza B
      virus than in cells infected with type A influenza virus and that the early
      induction of antiviral gene expression is mediated by the activation of the
      transcription factor IFN regulatory factor 3 (IRF3). We further demonstrate that
      influenza A virus infection activates IFN responses only after viral RNA (vRNA)
      synthesis, whereas influenza B virus induces IFN responses even if its
      infectivity is destroyed by UV treatment. Thus, initial viral transcription,
      replication, and viral protein synthesis are dispensable for influenza B virus
      induced antiviral responses. Moreover, vRNA molecules from both type A and B
      viruses are equally potent activators of IFN induction, but incoming influenza B
      virus structures are recognized directly in the cytosol, while influenza A virus
      is able to evade early recognition. Collectively, our data provide new evidence
      of a novel antiviral evasion strategy for influenza A virus without a
      contribution of the viral NS1 protein, and this opens up new insights into
      different influenza virus pathogenicities.

PMID- 22855503
TI  - T cell signaling targets for enhancing regulatory or effector function.
AB  - To respond to infection, resting or naive T cells must undergo activation, clonal
      expansion, and differentiation into specialized functional subsets of effector T
      cells. However, to prevent excessive or self-destructive immune responses,
      regulatory T cells (T(regs)) are instrumental in suppressing the activation and
      function of effector cells, including effector T cells. The transcription factor
      Forkhead box P3 (Foxp3) regulates the expression of genes involved in the
      development and function of T(regs). Foxp3 interacts with other transcription
      factors and with epigenetic elements such as histone deacetylases (HDACs) and
      histone acetyltransferases. T(reg) suppressive function can be increased by
      exposure to HDAC inhibitors. The individual contributions of different HDAC
      family members to T(reg) function and their respective mechanisms of action,
      however, remain unclear. A study showed that HDAC6, HDAC9, and Sirtuin-1 had
      distinct effects on Foxp3 expression and function, suggesting that selectively
      targeting HDACs individually or in combination may enhance T(reg) stability and
      suppressive function. Another study showed that the receptor programmed death 1
      (PD-1), a well-known inhibitor of T cell activation, halted cell cycle
      progression in effector T cells by inhibiting the transcription of the gene
      encoding the substrate-recognition component (Skp2) of the ubiquitin ligase
      SCF(Skp2). Together, these findings reveal new signaling targets for enhancing
      T(reg) or effector T cell function that may be helpful in designing future
      therapies, either to increase T(reg) suppressive function in transplantation and
      autoimmune diseases or to block PD-1 function, thus increasing the magnitude of
      antiviral or antitumor immune responses of effector T cells.

PMID- 22855504
TI  - Tyrosine kinases EnAbling adaptor molecules for chemokine-induced Rap1 activation
      in T cells.
AB  - Chemokines regulate T cell trafficking into secondary lymphoid organs and
      migration across endothelial cells in response to inflammatory signals. The small
      guanosine triphosphatase Rap1 is a critical regulator of chemokine signaling in T
      cells, but how chemokines activate Rap1 has been unclear. A study showed that Abl
      family tyrosine kinases were essential for chemokine-induced Rap1 activation, T
      cell polarization, and migration. Abl family kinases promoted Rap1 activation by
      phosphorylating the adaptor protein human enhancer of filamentation 1 (HEF1),
      thus establishing a critical Abl-HEF1-Rap1 signaling axis for chemokine-induced T
      cell migration.

PMID- 22855506
TI  - Differential RET signaling pathways drive development of the enteric lymphoid and
      nervous systems.
AB  - During the early development of the gastrointestinal tract, signaling through the
      receptor tyrosine kinase RET is required for initiation of lymphoid organ
      (Peyer's patch) formation and for intestinal innervation by enteric neurons. RET
      signaling occurs through glial cell line-derived neurotrophic factor (GDNF)
      family receptor alpha co-receptors present in the same cell (signaling in cis).
      It is unclear whether RET signaling in trans, which occurs in vitro through co
      receptors from other cells, has a biological role. We showed that the initial
      aggregation of hematopoietic cells to form lymphoid clusters occurred in a RET
      dependent, chemokine-independent manner through adhesion-mediated arrest of
      lymphoid tissue initiator (LTin) cells. Lymphoid tissue inducer cells were not
      necessary for this initiation phase. LTin cells responded to all RET ligands in
      trans, requiring factors from other cells, whereas RET was activated in enteric
      neurons exclusively by GDNF in cis. Furthermore, genetic and molecular approaches
      revealed that the versatile RET responses in LTin cells were determined by
      distinct patterns of expression of the genes encoding RET and its co-receptors.
      Our study shows that a trans RET response in LTin cells determines the initial
      phase of enteric lymphoid organ morphogenesis, and suggests that differential co
      expression of Ret and Gfra can control the specificity of RET signaling.

PMID- 22855505
TI  - The scaffolding protein synapse-associated protein 97 is required for enhanced
      signaling through isotype-switched IgG memory B cell receptors.
AB  - After their first encounter with a foreign antigen, naive B cells that have
      immunoglobulin M (IgM) B cell receptors (BCRs) trigger the primary antibody
      response and the generation of memory B cells with IgG BCRs. When these memory B
      cells reencounter the same antigen, the cell surface IgG BCRs stimulate their
      rapid differentiation into plasma cells that release large amounts of IgG
      antibodies. We showed that the conserved cytoplasmic tail of the IgG BCR, which
      contains a putative PDZ (postsynaptic density 95/disc large/zona occludens 1)
      binding motif, associated with synapse-associated protein 97 (SAP97), a PDZ
      domain-containing scaffolding molecule that is involved in controlling receptor
      density and signal strength at neuronal synapses. SAP97 accumulated and bound to
      IgG BCRs in the immunological synapses that formed in response to B cell
      engagement with antigen. Knocking down SAP97 in IgG+ B cells or mutating the
      putative PDZ-binding motif in the BCR tail impaired formation of the
      immunological synapse, initiation of IgG BCR signaling, and downstream activation
      of the mitogen-activated protein kinase p38. Thus, heightened B cell memory
      responses are encoded, in part, by a mechanism that involves SAP97 serving as a
      scaffolding protein in the IgG BCR immunological synapse.

PMID- 22855507
TI  - A measurement invariance examination of the Revised Child Anxiety and Depression
      Scale in a Southern sample: differential item functioning between African
      American and Caucasian youth.
AB  - This study examined the psychometric properties of the Revised Child Anxiety and
      Depression Scale in a large sample of youth from the Southern United States. The
      authors aimed to determine (a) if the established six-factor Revised Child
      Anxiety and Depression Scale structure could be replicated in this Southern
      sample and (b) if scores were associated with measurement invariance across
      African American and Caucasian youth representative of youth from this region of
      the United States. The established six-factor model evidenced the best fit in
      comparison to one-, two-, and five-factor models in the total sample (N =
      12,695), as well as in the African American (n = 4,906) and Caucasian (n = 6,667)
      subsamples. Multigroup confirmatory factor analysis also supported measurement
      invariance across African American and Caucasian youth at the levels of equal
      factor structure and equal factor loadings. Noninvariant item intercepts were
      identified, however, indicating differential functioning for a subset of items.
      Clinical and measurement implications of these findings are discussed and new
      norms are presented.

PMID- 22855508
TI  - Cross-validation of the PAI Negative Distortion Scale for feigned mental
      disorders: a research report.
AB  - A major strength of the Personality Assessment Inventory (PAI) is its systematic
      assessment of response styles, including feigned mental disorders. Recently,
      Mogge, Lepage, Bell, and Ragatz developed and provided the initial validation for
      the Negative Distortion Scale (NDS). Using rare symptoms as its detection
      strategy for feigning, the usefulness of NDS was examined via a known-groups
      comparison. The current study sought to cross-validate the NDS by implementing a
      between-subjects simulation design. Simulators were asked to feign total
      disability in an effort to secure unwarranted compensation from their insurance
      company. Even in an inpatient sample with severe Axis I disorders and concomitant
      impairment, the NDS proved effective as a rare-symptom strategy with low levels
      of item endorsement that remained mostly stable across genders. For construct
      validity, the NDS was moderately correlated with the Structured Interview of
      Reported Symptoms-Second Edition and other PAI feigning scales. For discriminant
      validity, it yielded a very large effect size (d = 1.81), surpassing the standard
      PAI feigning indicators. Utility estimates appeared to be promising for both
      ruling-out (low probability of feigning) and ruling-in (high probability of
      feigning) determinations at different base rates. Like earlier research, the data
      supported the creation of well-defined groups with indeterminate scores (i.e.,
      the cut score +/- 1 SEM) removed to avoid high rates of misclassifications for
      this narrow band.

PMID- 22855509
TI  - Scale- and item-level factor analyses of the VIA inventory of strengths.
AB  - The VIA Inventory of Strengths (VIA-IS) has emerged as the primary instrument for
      gauging individual strengths and virtues. Prior studies have generated
      inconsistent results concerning the latent structure of the VIA-IS. The present
      study attempted to address some of these inconsistencies. VIA-IS results from a
      large sample (N = 458,998) of U.S. adults who completed the inventory online were
      subjected to a series of principal components and factor analyses. The sample was
      66.46% female with a mean age of 34.36 years (SD = 14.13 years) and consistent
      with the general U.S. population in terms of geographic distribution. Information
      on ethnicity was not available. The size of the sample permitted both scale- and
      item-level analyses. The scale-level analyses produced findings similar to those
      of previous studies, but raised concerns about multidimensionality in the scales.
      Item-level analyses suggested an alternate set of 24 scales, 20 of which
      overlapped substantially with existing VIA-IS scales. A second-order analysis
      suggested five factors, including a new one labeled Future Orientation, versus
      the original six virtues proposed in the development of the VIA-IS. The results
      were used to speculate about elements of a second-generation model of strengths. 

PMID- 22855510
TI  - Prospective evaluation of a matrix-assisted laser desorption ionization-time of
      flight mass spectrometry system in a hospital clinical microbiology laboratory
      for identification of bacteria and yeasts: a bench-by-bench study for assessing
      the impact on time to identification and cost-effectiveness.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) has been found to be an accurate, rapid, and inexpensive method
      for the identification of bacteria and yeasts. Previous evaluations have compared
      the accuracy, time to identification, and costs of the MALDI-TOF MS method
      against standard identification systems or commercial panels. In this prospective
      study, we compared a protocol incorporating MALDI-TOF MS (MALDI protocol) with
      the current standard identification protocols (standard protocol) to determine
      the performance in actual practice using a specimen-based, bench-by-bench
      approach. The potential impact on time to identification (TTI) and costs had
      MALDI-TOF MS been the first-line identification method was quantitated. The MALDI
      protocol includes supplementary tests, notably for Streptococcus pneumoniae and
      Shigella, and indications for repeat MALDI-TOF MS attempts, often not measured in
      previous studies. A total of 952 isolates (824 bacterial isolates and 128 yeast
      isolates) recovered from 2,214 specimens were assessed using the MALDI protocol.
      Compared with standard protocols, the MALDI protocol provided identifications
      1.45 days earlier on average (P < 0.001). In our laboratory, we anticipate that
      the incorporation of the MALDI protocol can reduce reagent and labor costs of
      identification by $102,424 or 56.9% within 12 months. The model included the
      fixed annual costs of the MALDI-TOF MS, such as the cost of protein standards and
      instrument maintenance, and the annual prevalence of organisms encountered in our
      laboratory. This comprehensive cost analysis model can be generalized to other
      moderate- to high-volume laboratories.

PMID- 22855511
TI  - Comparative analysis of two broad-range PCR assays for pathogen detection in
      positive-blood-culture bottles: PCR-high-resolution melting analysis versus PCR
      mass spectrometry.
AB  - Detection of pathogens in bloodstream infections is important for directing
      antimicrobial treatment, but current culture-based approaches can be problematic.
      Broad-range PCR assays which target conserved genomic motifs for
      postamplification amplicon analysis permit detection of sepsis-causing pathogens.
      Comparison of different broad-range assays is important for informing future
      implementation strategies. In this study, we compared positive-blood-culture
      bottles processed by PCR coupled to high-resolution melting curve analysis
      (PCR/HRMA) and PCR coupled to electrospray ionization-mass spectrometry (PCR/ESI
      MS) to microbiology culture results. Genus-level concordance was 90% (confidence
      interval [CI], 80 to 96%) for PCR/HRMA and 94% (CI, 85 to 98%) for PCR/ESI-MS.
      Species-level concordance was 90% (CI, 80 to 96%) for PCR/HRMA and 86% (CI, 75 to
      93%) for PCR/ESI-MS. Unlike PCR/HRMA, PCR/ESI-MS was able to resolve
      polymicrobial samples. Our results demonstrated that the two assays have similar
      overall concordance rates but may have different roles as potential adjunctive
      tests with standard blood culture, since each method has different capabilities,
      advantages, and disadvantages.

PMID- 22855512
TI  - Genetic characterization of Trichomonas vaginalis isolates by use of multilocus
      sequence typing.
AB  - In this study, we introduce a multilocus sequence typing (MLST) scheme, comprised
      of seven single-copy housekeeping genes, to genetically characterize Trichomonas
      vaginalis. Sixty-eight historical and recent isolates of T. vaginalis were
      sampled from the American Type Culture Collection and female patients at area
      health care facilities, respectively, to assess the usefulness of this typing
      method. Forty-three polymorphic nucleotide sites, 51 different alleles, and 60
      sequence types were distinguished among the 68 isolates, revealing a diverse T.
      vaginalis population. Moreover, this discriminatory MLST scheme retains the
      ability to identify epidemiologically linked isolates such as those collected
      from sexual partners. Population genetic and phylogenetic analyses determined
      that T. vaginalis population structure is strongly influenced by recombination
      and is composed of two separate populations that may be nonclonal. MLST is useful
      for investigating the epidemiology, genetic diversity, and population structure
      of T. vaginalis.

PMID- 22855513
TI  - Aspergillus tanneri sp. nov., a new pathogen that causes invasive disease
      refractory to antifungal therapy.
AB  - The most common cause of invasive aspergillosis (IA) in patients with chronic
      granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans;
      other aspergilli rarely cause the disease. Here we review two clinical cases of
      fatal IA in CGD patients and describe a new etiologic agent of IA refractory to
      antifungal therapy. Unlike typical IA caused by A. fumigatus, the disease caused
      by the new species was chronic and spread from the lung to multiple adjacent
      organs. Mycological characteristics and the phylogenetic relationship with other
      aspergilli based on the sequence analysis of Mcm7, RPB2, and Tsr1 indicated that
      the new species, which we named as A. tanneri, belongs to Aspergillus section
      Circumdati. The species has a higher amphotericin B, voriconazole, and
      itraconazole MIC and causes more chronic infection in CGD mice than A. fumigatus.
      This is the first report documenting IA in CGD patients caused by a species
      belonging to the Aspergillus section Circumdati that is inherently resistant to
      azoles and amphotericin B. Unlike the results seen with many members of
      Aspergillus section Circumdati, ochratoxin was not detected in filtrates of
      cultures grown in various media. Our phenotypic and genetic characterization of
      the new species and the case reports will assist future diagnosis of infection
      caused by A. tanneri and lead to more appropriate patient management.

PMID- 22855514
TI  - Development of a real-time quantitative PCR for detecting duck hepatitis a virus
      genotype C.
AB  - Recently, duck hepatitis A virus genotype C (DHAV-C), a causative agent of duck
      viral hepatitis, has been responsible for increasing economic losses in the duck
      industry in China and South Korea. In this study, a real-time PCR assay targeting
      the 2C gene for detecting DHAV-C was developed. The assay was confirmed to be
      specific and sensitive, and the minimum detection limit was 3.36 * 10(3) copies
      per reaction, making this assay suitable for rapid diagnosis of DHAV-C infection
      from clinical samples. In addition, the dynamics of the viral loads in tissues of
      specific-pathogen-free (SPF) ducklings infected with DHAV-C were investigated
      using this method. The DHAV-C could be detected earliest in the liver within 12 h
      postinfection. Moreover, high viral loads were identified in the heart, liver,
      spleen, lung, kidney, bursa of Fabricius, thymus, pancreas, brain, and small
      intestine after 24 h postinfection. Taking the data collectively, the study
      described in this report is the first to have developed a real-time PCR method
      for detection of DHAV-C and thus contributes to pathogenicity research.

PMID- 22855515
TI  - Effects of storage on vancomycin and daptomycin MIC in susceptible blood isolates
      of methicillin-resistant Staphylococcus aureus.

PMID- 22855516
TI  - Emergence of methicillin-resistant Staphylococcus aureus ST239 with high-level
      mupirocin and inducible clindamycin resistance in a tertiary care center in
      Chennai, South India.

PMID- 22855517
TI  - Detection and serotyping of lyophilized nonculturable pneumococcal isolates.
AB  - One hundred fifty-two nonculturable lyophilized carriage pneumococcal isolates
      from a vaccine trial were subjected to PCR for serotyping, and 149 (98%) were
      successfully classified as vaccine or nonvaccine types, which were similar to
      viable isolates. The methodology will be useful for analysis of this and other
      studies where stored pneumococcal isolates fail to grow.

PMID- 22855518
TI  - Isolation and identification of Kroppenstedtia eburnea isolates from multiple
      patient samples.
AB  - No clinical isolates have been reported for the recently described
      thermoactinomycete Kroppenstedtia eburnea. Between 2006 and 2011, we obtained 14
      clinical isolates from patients in 9 U.S. states. Here we report growth
      characteristics, 16S rRNA gene sequencing, matrix-assisted laser desorption
      ionization-time of flight (MALDI-TOF) mass spectrometry-based identification, and
      antimicrobial susceptibility profiles of this recently described organism.

PMID- 22855519
TI  - Applying a real-time PCR assay for Histoplasma capsulatum to clinically relevant
      formalin-fixed paraffin-embedded human tissue.
AB  - A real-time PCR assay to detect Histoplasma capsulatum in formalin-fixed,
      paraffin-embedded (FFPE) tissue is described. The assay had an analytical
      sensitivity of 6 pg/MUl of fungal DNA, analytical specificity of 100%, and
      clinical sensitivity of 88.9%. This proof-of-concept study may aid in the
      diagnosis of histoplasmosis from FFPE tissue.

PMID- 22855520
TI  - Performance assessment of the DR. TBDR/NTM IVD kit for direct detection of
      Mycobacterium tuberculosis isolates, including rifampin-resistant isolates, and
      nontuberculous Mycobacteria.
AB  - We evaluated the performance of the DR. TBDR/NTM IVD kit, which was designed to
      detect Mycobacterium tuberculosis, rifampin-resistant M. tuberculosis, and
      nontuberculous mycobacteria, for detecting 110 positive and 50 negative cultures
      in Mycobacterium Growth Indicator Tubes. The accuracy rate of this kit for
      identification of Mycobacterium species was 95.5% (105/110).

PMID- 22855521
TI  - Could a peer-led intervention increase uptake of chlamydia screening? A proof of
      principle pilot study.
AB  - BACKGROUND: Uptake of the English National Chlamydia Screening Programme is lower
      than predicted necessary to result in a rapid fall in chlamydia prevalence. Peer
      led approaches may increase screening uptake but their feasibility and
      acceptability to young people is not known. METHODS: Focus groups and interviews
      with young women and men. Following interview, chlamydia postal kits were
      introduced to participants and their opinions on giving these out to their peers
      sought. Participants were asked for their views and experiences of discussing
      chlamydia screening and distributing kits to their friends 4-8 weeks after the
      focus group/interview. All kits returned to the laboratory over a 9-month period
      were recorded. RESULTS: Six men (mean age 19 years) and six women (mean age 20
      years) were recruited. In total 45 kits were distributed, 33 (73%) to female
      participants. 22 (67%) and 3 (25%) of kits given to females and males,
      respectively, were given to peers. Ten kits (22%; seven female, three male) all
      of which had been given out by females, were returned for testing. Participants
      generally felt positive about the idea of peer-led screening (PLS) using postal
      kits. However, embarrassment was a key theme, particularly among men. Generally
      women but not men were able to discuss PLS among their close friends. Both sexes
      felt PLS would be easier if kits were readily available in multiple sites, and
      chlamydia screening was more widely promoted. CONCLUSION: Female PLS but not male
      PLS was successful in recruiting peers to participate in chlamydia screening. An
      evaluation of the acceptability and cost-effectiveness of PLS is now indicated.

PMID- 22855522
TI  - Aeroplane headache and sinus barotrauma: any missing link?

PMID- 22855523
TI  - RIFL aims to be a new player in lipid metabolism.
AB  - RIFL (refeeding induced in fat and liver) is highly expressed in brown and white
      fat as well as in liver. In white adipose tissue and liver, RIFL expression is
      induced by refeeding and is also elevated in ob/ob mice. The function of RIFL is
      unknown, and there is some evidence to suggest it may be secreted. RIFL
      expression is induced during adipogenesis in rodent and human model systems, and
      cellular knockdown and mouse knockout studies demonstrate that RIFL expression
      correlates with lipid levels. Overall, these studies indicate that RIFL is a new
      important player in lipid metabolism.

PMID- 22855525
TI  - Association of Lis1 with outer arm dynein is modulated in response to alterations
      in flagellar motility.
AB  - The cytoplasmic dynein regulatory factor Lis1, which induces a persistent tight
      binding to microtubules and allows for transport of cargoes under high-load
      conditions, is also present in motile cilia/flagella. We observed that Lis1
      levels in flagella of Chlamydomonas strains that exhibit defective motility due
      to mutation of various axonemal substructures were greatly enhanced compared with
      wild type; this increase was absolutely dependent on the presence within the
      flagellum of the outer arm dynein alpha heavy chain/light chain 5 thioredoxin
      unit. To assess whether cells might interpret defective motility as a "high-load
      environment," we reduced the flagellar beat frequency of wild-type cells through
      enhanced viscous load and by reductive stress; both treatments resulted in
      increased levels of flagellar Lis1, which altered the intrinsic beat frequency of
      the trans flagellum. Differential extraction of Lis1 from wild-type and mutant
      axonemes suggests that the affinity of outer arm dynein for Lis1 is directly
      modulated. In cytoplasm, Lis1 localized to two punctate structures, one of which
      was located near the base of the flagella. These data reveal that the cell
      actively monitors motility and dynamically modulates flagellar levels of the
      dynein regulatory factor Lis1 in response to imposed alterations in beat
      parameters.

PMID- 22855524
TI  - The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1
      glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
AB  - The transport of glutamate receptors from the cell body to synapses is essential
      during neuronal development and may contribute to the regulation of synaptic
      strength in the mature nervous system. We previously showed that cyclin-dependent
      kinase-5 (CDK-5) positively regulates the abundance of GLR-1 glutamate receptors
      at synapses in the ventral nerve cord (VNC) of Caenorhabditis elegans. Here we
      identify a kinesin-3 family motor klp-4/KIF13 in a cdk-5 suppressor screen for
      genes that regulate GLR-1 trafficking. klp-4 mutants have decreased abundance of
      GLR-1 in the VNC. Genetic analysis of klp-4 and the clathrin adaptin unc-11/AP180
      suggests that klp-4 functions before endocytosis in the ventral cord. Time-lapse
      microscopy indicates that klp-4 mutants exhibit decreased anterograde flux of GLR
      1. Genetic analysis of cdk-5 and klp-4 suggests that they function in the same
      pathway to regulate GLR-1 in the VNC. Interestingly, GLR-1 accumulates in cell
      bodies of cdk-5 but not klp-4 mutants. However, GLR-1 does accumulate in klp-4
      mutant cell bodies if receptor degradation in the multivesicular body/lysosome
      pathway is blocked. This study identifies kinesin KLP-4 as a novel regulator of
      anterograde glutamate receptor trafficking and reveals a cellular control
      mechanism by which receptor cargo is targeted for degradation in the absence of
      its motor.

PMID- 22855526
TI  - A nuclear-derived proteinaceous matrix embeds the microtubule spindle apparatus
      during mitosis.
AB  - The concept of a spindle matrix has long been proposed. Whether such a structure
      exists, however, and what its molecular and structural composition are have
      remained controversial. In this study, using a live-imaging approach in
      Drosophila syncytial embryos, we demonstrate that nuclear proteins reorganize
      during mitosis to form a highly dynamic, viscous spindle matrix that embeds the
      microtubule spindle apparatus, stretching from pole to pole. We show that this
      "internal" matrix is a distinct structure from the microtubule spindle and from a
      lamin B-containing spindle envelope. By injection of 2000-kDa dextran, we show
      that the disassembling nuclear envelope does not present a diffusion barrier.
      Furthermore, when microtubules are depolymerized with colchicine just before
      metaphase the spindle matrix contracts and coalesces around the chromosomes,
      suggesting that microtubules act as "struts" stretching the spindle matrix. In
      addition, we demonstrate that the spindle matrix protein Megator requires its
      coiled-coil amino-terminal domain for spindle matrix localization, suggesting
      that specific interactions between spindle matrix molecules are necessary for
      them to form a complex confined to the spindle region. The demonstration of an
      embedding spindle matrix lays the groundwork for a more complete understanding of
      microtubule dynamics and of the viscoelastic properties of the spindle during
      cell division.

PMID- 22855527
TI  - GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic
      stem cell differentiation.
AB  - GATA-6 is a zinc-finger transcription factor essential for early embryogenesis.
      Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis
      of epiblast cells. The endoderm defects have been attributed to the loss of HNF4,
      disabled-2, and GATA-4. However, the mechanisms underlying epiblast apoptosis are
      unclear. In this study we used mouse embryonic stem cell-derived embryoid bodies
      (EBs) as a model for peri-implantation development and found that ablation of
      GATA-6 causes massive apoptosis during EB differentiation. Endoderm grafting
      experiments and ectopic basement membrane (BM) assembly suggest that both BM and
      non-BM factors contribute to cell survival. Furthermore, the increased cell death
      in mutant EBs is accompanied by reduced expression of bone morphogenetic protein
      2 (BMP-2). Chromatin immunoprecipitation reveals direct binding of GATA-6 to the
      Bmp2 promoter. Treatment of the mutant EBs with BMP-2 markedly suppresses
      apoptosis, whereas stable overexpression of the BMP antagonist noggin or a
      dominant-negative BMP receptor in normal EBs leads to increased apoptosis. Last,
      activation of SMAD1/5 by phosphorylation is significantly inhibited in the
      absence of GATA-6, and this is reversed by exogenous BMP-2. Treatment of normal
      EBs with SMAD phosphorylation inhibitor increases apoptosis. Collectively these
      results suggest that GATA-6 promotes cell survival by regulating endoderm
      expression of BMP-2 and BM during embryonic epithelial morphogenesis.

PMID- 22855528
TI  - Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells
      via a galectin-9-dependent mechanism.
AB  - The sialomucin endolyn is implicated in adhesion, migration, and differentiation
      of various cell types. Along rat kidney tubules, endolyn is variously localized
      to the apical surface and endosomal/lysosomal compartments. Apical delivery of
      newly synthesized rat endolyn predominates over direct lysosomal delivery in
      polarized Madin-Darby canine kidney cells. Apical sorting depends on terminal
      processing of a subset of lumenal N-glycans. Here we dissect the requirements of
      N-glycan processing for apical targeting and investigate the underlying
      mechanism. Modulation of glycan branching and subsequent polylactosamine
      elongation by knockdown of N-acetylglucosaminyltransferase III or V had no effect
      on apical delivery of endolyn. In contrast, combined but not individual knockdown
      of sialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are
      responsible for addition of alpha2,3- and alpha2,6-linked sialic acids on N
      glycans, dramatically decreased endolyn surface polarity. Endolyn synthesized in
      the presence of kifunensine, which blocks terminal N-glycan processing, reduced
      its interaction with several recombinant canine galectins, and knockdown of
      galectin-9 (but not galectin-3, -4, or -8) selectively disrupted endolyn
      polarity. Our data suggest that sialylation enables recognition of endolyn by
      galectin-9 to mediate efficient apical sorting. They raise the intriguing
      possibility that changes in glycosyltransferase expression patterns and/or
      galectin-9 distribution may acutely modulate endolyn trafficking in the kidney.

PMID- 22855529
TI  - SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles.
AB  - The mammalian cell nucleus is compartmentalized into nonmembranous subnuclear
      domains that regulate key nuclear functions. Nuclear speckles are subnuclear
      domains that contain pre-mRNA processing factors and noncoding RNAs. Many of the
      nuclear speckle constituents work in concert to coordinate multiple steps of gene
      expression, including transcription, pre-mRNA processing and mRNA transport. The
      mechanism that regulates the formation and maintenance of nuclear speckles in the
      interphase nucleus is poorly understood. In the present study, we provide
      evidence for the involvement of nuclear speckle resident proteins and RNA
      components in the organization of nuclear speckles. SR-family splicing factors
      and their binding partner, long noncoding metastasis-associated lung
      adenocarcinoma transcript 1 RNA, can nucleate the assembly of nuclear speckles in
      the interphase nucleus. Depletion of SRSF1 in human cells compromises the
      association of splicing factors to nuclear speckles and influences the levels and
      activity of other SR proteins. Furthermore, on a stably integrated reporter gene
      locus, we demonstrate the role of SRSF1 in RNA polymerase II-mediated
      transcription. Our results suggest that SR proteins mediate the assembly of
      nuclear speckles and regulate gene expression by influencing both transcriptional
      and posttranscriptional activities within the cell nucleus.

PMID- 22855530
TI  - Drosophila tubulin-binding cofactor B is required for microtubule network
      formation and for cell polarity.
AB  - Microtubules (MTs) are essential for cell division, shape, intracellular
      transport, and polarity. MT stability is regulated by many factors, including MT
      associated proteins and proteins controlling the amount of free tubulin
      heterodimers available for polymerization. Tubulin-binding cofactors are
      potential key regulators of free tubulin concentration, since they are required
      for alpha-beta-tubulin dimerization in vitro. In this paper, we show that
      mutation of the Drosophila tubulin-binding cofactor B (dTBCB) affects the levels
      of both alpha- and beta-tubulins and dramatically destabilizes the MT network in
      different fly tissues. However, we find that dTBCB is dispensable for the early
      MT-dependent steps of oogenesis, including cell division, and that dTBCB is not
      required for mitosis in several tissues. In striking contrast, the absence of
      dTBCB during later stages of oogenesis causes major defects in cell polarity. We
      show that dTBCB is required for the polarized localization of the axis
      determining mRNAs within the oocyte and for the apico-basal polarity of the
      surrounding follicle cells. These results establish a developmental function for
      the dTBCB gene that is essential for viability and MT-dependent cell polarity,
      but not cell division.

PMID- 22855531
TI  - Nonredundant roles of cytoplasmic beta- and gamma-actin isoforms in regulation of
      epithelial apical junctions.
AB  - Association with the actin cytoskeleton is critical for normal architecture and
      dynamics of epithelial tight junctions (TJs) and adherens junctions (AJs).
      Epithelial cells express beta-cytoplasmic (beta-CYA) and gamma-cytoplasmic (gamma
      CYA) actins, which have different cellular localization and functions. This study
      elucidates the roles of cytoplasmic actins in regulating structure and remodeling
      of AJs and TJs in model intestinal epithelia. Immunofluorescence labeling and
      latrunculin B treatment reveal affiliation of dynamic beta-CYA filaments with
      newly assembled and mature AJs, whereas an apical gamma-CYA pool is composed of
      stable perijunctional bundles and rapidly turning-over nonjunctional filaments.
      The functional effects of cytoplasmic actins on epithelial junctions are examined
      by using isoform-specific small interfering RNAs and cell-permeable inhibitory
      peptides. These experiments demonstrate unique roles of beta-CYA and gamma-CYA in
      regulating the steady-state integrity of AJs and TJs, respectively. Furthermore,
      beta-CYA is selectively involved in establishment of apicobasal cell polarity.
      Both actin isoforms are essential for normal barrier function of epithelial
      monolayers, rapid AJ/TJ reassembly, and formation of three-dimensional cysts.
      Cytoplasmic actin isoforms play unique roles in regulating structure and
      permeability of epithelial junctions.

PMID- 22855536
TI  - Contrasting patterns of X/Y polymorphism distinguish Carica papaya from other sex
      chromosome systems.
AB  - The sex chromosomes of the tropical crop papaya (Carica papaya) are
      evolutionarily young and consequently allow for the examination of evolutionary
      mechanisms that drive early sex chromosome divergence. We conducted a molecular
      population genetic analysis of four X/Y gene pairs from a collection of 45 wild
      papaya accessions. These population genetic analyses reveal striking differences
      in the patterns of polymorphism between the X and Y chromosomes that distinguish
      them from other sex chromosome systems. In most sex chromosome systems, the Y
      chromosome displays significantly reduced polymorphism levels, whereas the X
      chromosome maintains a level of polymorphism that is comparable to autosomal
      loci. However, the four papaya sex-linked loci that we examined display diversity
      patterns that are opposite this trend: the papaya X alleles exhibit significantly
      reduced polymorphism levels, whereas the papaya Y alleles maintain greater than
      expected levels of diversity. Our analyses suggest that selective sweeps in the
      regions of the X have contributed to this pattern while also revealing
      geographically restricted haplogroups on the Y. We discuss the possible role
      sexual selection and/or genomic conflict have played in shaping the contrasting
      patterns of polymorphism found for the papaya X and Y chromosomes.

PMID- 22855532
TI  - The essential iron-sulfur protein Rli1 is an important target accounting for
      inhibition of cell growth by reactive oxygen species.
AB  - Oxidative stress mediated by reactive oxygen species (ROS) is linked to
      degenerative conditions in humans and damage to an array of cellular components.
      However, it is unclear which molecular target(s) may be the primary "Achilles'
      heel" of organisms, accounting for the inhibitory action of ROS. Rli1p (ABCE1) is
      an essential and highly conserved protein of eukaryotes and archaea that requires
      notoriously ROS-labile cofactors (Fe-S clusters) for its functions in protein
      synthesis. In this study, we tested the hypothesis that ROS toxicity is caused by
      Rli1p dysfunction. In addition to being essential, Rli1p activity (in nuclear
      ribosomal-subunit export) was shown to be impaired by mild oxidative stress in
      yeast. Furthermore, prooxidant resistance was decreased by RLI1 repression and
      increased by RLI1 overexpression. This Rlip1 dependency was abolished during
      anaerobicity and accentuated in cells expressing a FeS cluster-defective Rli1p
      construct. The protein's FeS clusters appeared ROS labile during in vitro
      incubations, but less so in vivo. Instead, it was primarily (55)FeS-cluster
      supply to Rli1p that was defective in prooxidant-exposed cells. The data indicate
      that, owing to its essential nature but dependency on ROS-labile FeS clusters,
      Rli1p function is a primary target of ROS action. Such insight could help inform
      new approaches for combating oxidative stress-related disease.

PMID- 22855533
TI  - Actin polymerization controls the activation of multidrug efflux at fertilization
      by translocation and fine-scale positioning of ABCB1 on microvilli.
AB  - Fertilization changes the structure and function of the cell surface. In sea
      urchins, these changes include polymerization of cortical actin and a coincident,
      switch-like increase in the activity of the multidrug efflux transporter ABCB1a.
      However, it is not clear how cortical reorganization leads to changes in membrane
      transport physiology. In this study, we used three-dimensional superresolution
      fluorescence microscopy to resolve the fine-scale movements of the transporter
      along polymerizing actin filaments, and we show that efflux activity is
      established after ABCB1a translocates to the tips of the microvilli. Inhibition
      of actin polymerization or bundle formation prevents tip localization, resulting
      in the patching of ABCB1a at the cell surface and decreased efflux activity. In
      contrast, enhanced actin polymerization promotes tip localization. Finally,
      interference with Rab11, a regulator of apical recycling, inhibits activation of
      efflux activity in embryos. Together our results show that actin-mediated, short
      range traffic and positioning of transporters at the cell surface regulates
      multidrug efflux activity and highlight the multifaceted roles of microvilli in
      the spatial distribution of membrane proteins.

PMID- 22855535
TI  - Novel PKCalpha-mediated phosphorylation site(s) on cofilin and their potential
      role in terminating histamine release.
AB  - Using specific inhibitors, kinase-negative mutants, and small interfering RNA
      against protein kinase Calpha (PKCalpha) or PKCbetaI, we find that PKCbetaI
      positively regulates degranulation in rat basophilic leukemia-2H3 cells, whereas
      PKCalpha negatively regulates degranulation. Mass spectrometric and mutagenic
      analyses reveal that PKCalpha phosphorylates cofilin at Ser-23 and/or Ser-24
      during degranulation. Overexpression of a nonphosphorylatable form (S23,24A), but
      not that of a mutant-mimicking phosphorylated form (S23,24E), increases
      degranulation. Furthermore, the S23,24A mutant binds to F-actin and retains its
      depolymerizing and/or cleavage activity; conversely, the S23,24E mutant is unable
      to sever actin filaments, resulting in F-actin polymerization. In addition, the
      S23,24E mutant preferentially binds to the 14-3-3zeta protein. Fluorescence
      activated cell sorting analysis with fluorescein isothiocyanate-phalloidin and
      simultaneous observation of degranulation, PKC translocation, and actin
      polymerization reveals that during degranulation, actin polymerization is
      dependent on PKCalpha activity. These results indicate that a novel PKCalpha
      mediated phosphorylation event regulates cofilin by inhibiting its ability to
      depolymerize F-actin and bind to 14-3-3zeta, thereby promoting F-actin
      polymerization, which is necessary for cessation of degranulation.

PMID- 22855534
TI  - BiP prevents rod opsin aggregation.
AB  - Mutations in rod opsin-the light-sensitive protein of rod cells-cause retinitis
      pigmentosa. Many rod opsin mutations lead to protein misfolding, and therefore it
      is important to understand the role of molecular chaperones in rod opsin
      biogenesis. We show that BiP (HSPA5) prevents the aggregation of rod opsin.
      Cleavage of BiP with the subtilase cytotoxin SubAB results in endoplasmic
      reticulum (ER) retention and ubiquitylation of wild-type (WT) rod opsin (WT-green
      fluorescent protein [GFP]) at the ER. Fluorescence recovery after photobleaching
      reveals that WT-GFP is usually mobile in the ER. By contrast, depletion of BiP
      activity by treatment with SubAB or coexpression of a BiP ATPase mutant,
      BiP(T37G), decreases WT-GFP mobility to below that of the misfolding P23H mutant
      of rod opsin (P23H-GFP), which is retained in the ER and can form cytoplasmic
      ubiquitylated inclusions. SubAB treatment of P23H-GFP-expressing cells decreases
      the mobility of the mutant protein further and leads to ubiquitylation throughout
      the ER. Of interest, BiP overexpression increases the mobility of P23H-GFP,
      suggesting that it can reduce mutant rod opsin aggregation. Therefore inhibition
      of BiP function results in aggregation of rod opsin in the ER, which suggests
      that BiP is important for maintaining the solubility of rod opsin in the ER.

PMID- 22855537
TI  - Evolutionary genetics of the hydroid allodeterminant alr2.
AB  - We surveyed genetic variation in alr2, an allodeterminant of the colonial hydroid
      Hydractinia symbiolongicarpus. We generated cDNA from a sample of 239 Hydractinia
      colonies collected at Lighthouse Point, Connecticut, and identified 473 alr2
      alleles, 198 of which were unique. Rarefaction analysis suggested that the sample
      was near saturation. Most alleles were rare, with 86% occurring at frequencies of
      1% or less. Alleles were highly variable, diverging on average by 18% of the
      amino acids in a predicted extracellular domain of the molecule. Analysis of 152
      full-length alleles confirmed the existence of two structural types, defined by
      exons 4-8 of the gene. Several residues of the predicted immunoglobulin
      superfamily-like domains display signatures of positive selection. We also
      identified 77 unique alr2 pseudogene sequences from 85 colonies. Twenty-seven of
      these sequences matched expressed alr2 sequences from other colonies. This
      observation is consistent with pseudogenes contributing to alr2 diversification
      through sequence donation. A more limited collection of animals was made from a
      distant, relict population of H. symbiolongicarpus. Sixty percent of the unique
      sequences identified in this sample were found to match sequences from the
      Lighthouse Point population. The large number of alr2 alleles, their degree of
      divergence, the predominance of rare alleles in the population, their persistence
      over broad spatial and temporal scales, and the signatures of positive selection
      in multiple residues of the putative recognition domain paint a consistent
      picture of negative-frequency-dependent selection operating in this system. The
      genetic diversity observed at alr2 is comparable to that of the most highly
      polymorphic genetic systems known to date.

PMID- 22855538
TI  - White and gray matter impairment in chronic obstructive pulmonary disease: what's
      the matter?

PMID- 22855539
TI  - Endobronchial ultrasound in mediastinal lymphadenopathy: cutting costs not
      patients?

PMID- 22855541
TI  - Venous thromboembolism prophylaxis, shorter courses of isoniazid for
      tuberculosis, and the microbiome in asthma.

PMID- 22855540
TI  - Progress in pulmonary arterial hypertension pathology: relighting a torch inside
      the tunnel.

PMID- 22855542
TI  - Pulmonary sequestration syndrome diagnosed from a Nocardia infection.

PMID- 22855543
TI  - Subclinical interstitial lung disease: no place for crackles?

PMID- 22855544
TI  - Fatalism is not justified when evaluating the critically ill elderly.

PMID- 22855545
TI  - Favorable effect of sorafenib in a patient with neurofibromatosis-associated
      pulmonary hypertension.

PMID- 22855546
TI  - Pseudobronchiectasis after pertussis and mycoplasma infection.

PMID- 22855547
TI  - Scattered lung cysts as the main radiographic finding of constrictive
      bronchiolitis.

PMID- 22855548
TI  - A solitary pulmonary nodule mimicking lung cancer.

PMID- 22855549
TI  - Expression of concern: Dysregulation of claudin-5 in HIV-induced interstitial
      pneumonitis and lung vascular injury: protective role of PPAR-gamma.

PMID- 22855550
TI  - Tuberculosis elimination in the United States: an achievable goal or an illusion?

PMID- 22855551
TI  - Investigation of the skin sensitizing properties of 5 osmolytic prodrugs in a
      weight-of-evidence assessment, employing in silico, in vivo, and read across
      analyses.
AB  - The amino acid esters ethyl glycinate (EG), DL-alpha-tocopheryl-(mono-)betainate
      hydrochloride (TMB), DL-alpha-tocopheryl-(mono-)glycinate hydrochloride (TMG), DL
      alpha-tocopheryl-(mono-)prolinate hydrochloride (TMP), and DL-alpha-tocopheryl
      (mono-)sarcosinate hydrochloride (TMS) were previously shown to exert an
      osmoprotective function to human skin in vitro. Based on literature data, the
      parent compounds alpha-tocopherol (vitamin E) and the amino acids glycine,
      betaine (trimethylated glycine), proline, and sarcosine (N-methylated glycine)
      are not considered to be sensitizers. To investigate skin sensitizing properties
      of the esters, EG, TMG, and TMP were tested in the Local Lymph Node Assay (LLNA).
      Remaining esters were assessed by read across analysis considering structural
      similarities and mechanistic aspects. The LLNA results were consistent with in
      silico outcomes from ToxTree 2.5.0 indicative for protein binding; EG was
      negative; TMG and TMP were positive. Since TMB and TMS showed structural
      similarities to TMG and TMP and were also positive in ToxTree, it was concluded
      that both TMB and TMS can also be expected to have a skin sensitizing potential
      and therefore animal testing was waived.

PMID- 22855552
TI  - Long-term survival among Hodgkin's lymphoma patients with gastrointestinal
      cancer: a population-based study.
AB  - BACKGROUND: The increased risk of gastrointestinal (GI) cancers after Hodgkin's
      lymphoma (HL) is well established. However, no large population-based study has
      described the actuarial survival after subsequent GI cancers in HL survivors (HL
      GI). PATIENTS AND METHODS: For 209 patients with HL-GI cancers (105 colon, 35
      stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with
      first primary GI cancers (GI-1), actuarial survival was compared, accounting for
      age, gender, race, GI cancer stage, radiation for HL, and other variables.
      RESULTS: Though survival of HL patients who developed localized stage colon
      cancer was similar to that of the GI-1 group, overall survival (OS) of HL
      patients with regional or distant stage colon cancer was reduced [hazard ratio,
      (HR)=1.46, P=0.01]. The HL survivors with regional or distant stage colon cancer
      in the transverse segment had an especially high risk of mortality (HR: 2.7,
      P=0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors
      (HR=3.46, P=0.006). CONCLUSIONS: The HL patients who develop GI cancer experience
      significantly reduced survival compared with patients with a first primary GI
      cancer. Further research is needed to explain the inferior survival of HL
      patients and to define selection criteria for cancer screening in HL survivors.

PMID- 22855553
TI  - Meat consumption and risk of lung cancer: evidence from observational studies.
AB  - BACKGROUND: A number of epidemiological studies have reported inconsistent
      findings on the association between meat consumption and lung cancer. DESIGN: We
      therefore conducted a systematic review and meta-analysis to investigate the
      relationship between meat consumption and lung cancer risk in epidemiological
      studies. RESULTS: Twenty-three case-control and 11 cohort studies were included.
      All studies adjusted for smoking or conducted in never smokers. The summary
      relative risks (RRs) of lung cancer for the highest versus lowest intake
      categories were 1.35 (95% confidence interval (CI) 1.08-1.69) for total meat,
      1.34 (95% CI 1.18-1.52) for red meat, and 1.06 (95% CI 0.90-1.25) for processed
      meat. An inverse association was found between poultry intake and lung cancer (RR
      = 0.91, 95% CI 0.85-0.97), but not for total white meat (RR = 1.06, 95% CI 0.82
      1.37) or fish (RR = 1.01, 95% CI 0.96-1.07). CONCLUSIONS: The relationship
      between meat intake and lung cancer risk appears to depend on the types of meat
      consumed. A high intake of red meat may increase the risk of lung cancer by about
      35%, while a high intake of poultry decreases the risk by about 10%. More well
      designed cohort studies on meat mutagens or heme iron, meat cooking preferences,
      and doneness level are needed to fully characterize this meat-lung cancer
      association.

PMID- 22855554
TI  - Myocardial perfusion reserve assessed by T2-prepared steady-state free precession
      blood oxygen level-dependent magnetic resonance imaging in comparison to
      fractional flow reserve.
AB  - BACKGROUND: Blood oxygen level-dependent (BOLD) cardiac magnetic resonance
      imaging (CMR) has been shown to be able to detect myocardial perfusion
      differences. However, validation of BOLD CMR against fractional flow reserve
      (FFR) is lacking. The aim of our study was to analyze the potential diagnostic
      accuracy of BOLD CMR in comparison to invasively measured FFR, which served as
      gold standard for a hemodynamic significant coronary lesion. METHODS AND RESULTS:
      BOLD image was performed at rest and during adenosine infusion in a 1.5-T CMR
      scanner. Thirty-six patients were analyzed for relative BOLD signal intensity
      increase according to the 16-segment model. Invasive FFR measurements were
      performed in the 3 major coronary arteries during adenosine infusion in all
      patients. An FFR<=0.8 was regarded to indicate a significant coronary lesion.
      Relative BOLD signal intensity increase was significantly lower in myocardial
      segments supplied by coronary arteries with an FFR<=0.8 compared with segments
      with an FFR>0.8 (1.1+/-0.2 versus 1.5+/-0.2; P<0.0001). Sensitivity and
      specificity yielded 88.2% and 89.5%, respectively. CONCLUSIONS: CMR BOLD imaging
      reliably detects hemodynamic significant coronary artery disease and is, thus, an
      alternative to contrast-enhanced perfusion studies.

PMID- 22855555
TI  - Mouse estrous cycle regulation of vaginal versus uterine cytokines, chemokines,
      alpha-/beta-defensins and TLRs.
AB  - This study investigates the cyclic changes in innate immunity in the female
      reproductive tract (FRT) of mice during the estrous cycle. By examining uterine
      and vaginal tissues and secretions we show that innate immunity varies with the
      stage of the estrous cycle and site in the FRT. Secretions from the uterine lumen
      contained cytokines and chemokines that were significantly higher at proestrus
      and estrus relative to that measured at diestrus. In contrast, analysis of
      vaginal secretions indicated that only IL-1beta and CXCL1/mouse KC changed during
      the cycle, with highest levels measured at diestrus and estrus. In contrast,
      vaginal alpha-defensin 2 and beta-defensins 1-4 mRNA levels peaked at proestrus
      and estrus and are expressed 1-4 logs greater than that seen in the uterus. These
      studies further indicate that TLR5 and TLR12 in the uterus, and TLR1, TLR2, TLR5
      and TLR13 in the vagina varies with stage of the estrous cycle, with some peaking
      at proestrus/estrus and others at diestrus. Overall, these studies indicate that
      innate immune parameters in the uterus and vagina are separate and discrete, and
      regulated precisely during the estrous cycle.

PMID- 22855556
TI  - In vivo cardiac myosin binding protein C gene transfer rescues myofilament
      contractile dysfunction in cardiac myosin binding protein C null mice.
AB  - BACKGROUND: Decreased expression of cardiac myosin binding protein C (cMyBPC) in
      the heart has been implicated as a consequence of mutations in cMyBPC that lead
      to abnormal contractile function at the myofilament level, thereby contributing
      to the development of hypertrophic cardiomyopathy in humans. It has not been
      established whether increasing the levels of cMyBPC in the intact heart can
      improve myofilament and in vivo contractile function and attenuate maladaptive
      remodeling processes because of reduced levels of cMyBPC. METHODS AND RESULTS: We
      performed in vivo gene transfer of cMyBPC by direct injection into the myocardium
      of cMyBPC-deficient (cMyBPC(-/-)) mice, and mechanical experiments were conducted
      on skinned myocardium isolated from cMyBPC(-/-) hearts 21 days and 20 weeks after
      gene transfer. Cross-bridge kinetics in skinned myocardium isolated from cMyBPC(
      /-) hearts after cMyBPC gene transfer were significantly slower compared with
      untreated cMyBPC(-/-) myocardium and were comparable to wild-type myocardium and
      cMyBPC(-/-) myocardium that was reconstituted with recombinant cMyBPC in vitro.
      cMyBPC content in cMyBPC(-/-) skinned myocardium after in vivo cMyBPC gene
      transfer or in vitro cMyBPC reconstitution was similar to wild-type levels. In
      vivo echocardiography studies of cMyBPC(-/-) hearts after cMyBPC gene transfer
      revealed improved systolic and diastolic contractile function and reductions in
      left ventricular wall thickness. CONCLUSIONS: This proof-of-concept study
      demonstrates that gene therapy designed to increase expression of cMyBPC in the
      cMyBPC-deficient myocardium can improve myofilament and in vivo contractile
      function, suggesting that cMyBPC gene therapy may be a viable approach for
      treatment of cardiomyopathies because of mutations in cMyBPC.

PMID- 22855557
TI  - Effect of beta-blocker cessation on chronotropic incompetence and exercise
      tolerance in patients with advanced heart failure.
AB  - BACKGROUND: Chronotropic incompetence is defined as the inability to reach 80% of
      heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The
      presence of chronotropic incompetence is associated with reduced peak oxygen
      consumption, and rate-responsive pacing therapy is under investigation to improve
      exercise capacity in heart failure (HF). However, uncertainty exists about
      whether chronotropic incompetence and reduced exercise tolerance in HF are
      attributable to beta-blockade. METHODS AND RESULTS: Subjects with HF and
      receiving long-term beta-blocker therapy underwent cardiopulmonary exercise
      tolerance testing under 2 conditions in random sequence: (1) after a 27-hour
      washout period (Off-BB) and (2) 3 hours after beta-blocker ingestion (On-BB).
      Norepinephrine levels were drawn at rest and at peak exercise. beta1-response to
      norepinephrine was assessed using the chronotropic responsiveness index:
      DeltaHR/Deltalog norepinephrine. Nineteen patients with systolic HF (left
      ventricular ejection fraction, 22.8+/-7.7%) were enrolled. Mean age was 49.4+/
      12.3 years. Average carvedilol equivalent dose was 29.1+/-17.0 mg daily. Peak HR
      off/on beta-blockers was 62.7+/-18.7% and 51.4+/-18.2% HR reserve (P<0.01) and
      79.1+/-11.0% and 70.3+/-12.3% maximally predicted HR (P<0.01). For the Off-BB and
      On-BB conditions, the respiratory exchange ratios were 1.05+/-0.06 and 1.05+/
      0.10 (P=0.77), respectively, confirming maximal and near identical effort in both
      conditions. The peak oxygen consumption was 16.6+/-3.34 and 15.9+/-3.31 mL/kg/min
      (P=0.03), and the chronotropic responsiveness index was 19.3+/-7.2 and 16.2+/-7.1
      (P=0.18). CONCLUSIONS: Acute beta-blocker cessation does not normalize the
      chronotropic response to exercise in patients with advanced HF and chronotropic
      incompetence.

PMID- 22855558
TI  - Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6
      holocomplex.
AB  - Faithful chromosome segregation in meiosis is crucial to form viable, healthy
      offspring and in most species, it requires programmed recombination between
      homologous chromosomes. In fission yeast, meiotic recombination is initiated by
      Rec12 (Spo11 homolog) and generates single Holliday junction (HJ) intermediates,
      which are resolved by the Mus81-Eme1 endonuclease to generate crossovers and
      thereby allow proper chromosome segregation. Although Mus81 contains the active
      site for HJ resolution, the regulation of Mus81-Eme1 is unclear. In cells lacking
      Nse5-Nse6 of the Smc5-Smc6 genome stability complex, we observe persistent
      meiotic recombination intermediates (DNA joint molecules) resembling HJs that
      accumulate in mus81Delta cells. Elimination of Rec12 nearly completely rescues
      the meiotic defects of nse6Delta and mus81Delta single mutants and partially
      rescues nse6Delta mus81Delta double mutants, indicating that these factors act
      after DNA double-strand break formation. Likewise, expression of the bacterial HJ
      resolvase RusA partially rescues the defects of nse6Delta, mus81Delta and
      nse6Delta mus81Delta mitotic cells, as well as the meiotic defects of nse6Delta
      and mus81Delta cells. Partial rescue likely reflects the accumulation of
      structures other than HJs, such as hemicatenanes, and an additional role for Nse5
      Nse6 most prominent during mitotic growth. Our results indicate a regulatory role
      for the Smc5-Smc6 complex in HJ resolution via Mus81-Eme1.

PMID- 22855559
TI  - Analysis of the epigenetic status of telomeres by using ChIP-seq data.
AB  - The chromatin structure of eukaryotic telomeres plays an essential role in
      telomere functions. However, their study might be impaired by the presence of
      interstitial telomeric sequences (ITSs), which have a widespread distribution in
      different model systems. We have developed a simple approach to study the
      chromatin structure of Arabidopsis telomeres independently of ITSs by analyzing
      ChIP-seq data. This approach could be used to study the chromatin structure of
      telomeres in some other eukaryotes. The analysis of ChIP-seq experiments revealed
      that Arabidopsis telomeres have higher density of histone H3 than centromeres,
      which might reflects their short nucleosomal organization. These experiments also
      revealed that Arabidopsis telomeres have lower levels of heterochromatic marks
      than centromeres (H3K9(Me2) and H3K27(Me)), higher levels of some euchromatic
      marks (H3K4(Me2) and H3K9Ac) and similar or lower levels of other euchromatic
      marks (H3K4(Me3), H3K36(Me2), H3K36(Me3) and H3K18Ac). Interestingly, the ChIP
      seq experiments also revealed that Arabidopsis telomeres exhibit high levels of
      H3K27(Me3), a repressive mark that associates with many euchromatic genes. The
      epigenetic profile of Arabidopsis telomeres is closely related to the previously
      defined chromatin state 2. This chromatin state is found in 23% of Arabidopsis
      genes, many of which are repressed or lowly expressed. At least, in part, this
      scenario is similar in rice.

PMID- 22855560
TI  - Cell type-specific genomics of Drosophila neurons.
AB  - Many tools are available to analyse genomes but are often challenging to use in a
      cell type-specific context. We have developed a method similar to the isolation
      of nuclei tagged in a specific cell type (INTACT) technique [Deal,R.B. and
      Henikoff,S. (2010) A simple method for gene expression and chromatin profiling of
      individual cell types within a tissue. Dev. Cell, 18, 1030-1040; Steiner,F.A.,
      Talbert,P.B., Kasinathan,S., Deal,R.B. and Henikoff,S. (2012) Cell-type-specific
      nuclei purification from whole animals for genome-wide expression and chromatin
      profiling. Genome Res., doi:10.1101/gr.131748.111], first developed in plants,
      for use in Drosophila neurons. We profile gene expression and histone
      modifications in Kenyon cells and octopaminergic neurons in the adult brain. In
      addition to recovering known gene expression differences, we also observe
      significant cell type-specific chromatin modifications. In particular, a small
      subset of differentially expressed genes exhibits a striking anti-correlation
      between repressive and activating histone modifications. These genes are enriched
      for transcription factors, recovering those known to regulate mushroom body
      identity and predicting analogous regulators of octopaminergic neurons. Our
      results suggest that applying INTACT to specific neuronal populations can
      illuminate the transcriptional regulatory networks that underlie neuronal cell
      identity.

PMID- 22855562
TI  - Ectopic expression of human telomerase RNA component results in increased
      telomerase activity and elongated telomeres in bovine blastocysts.
AB  - Telomeres play an important role in aging, and are critical for the regenerative
      capacity of mammalian cells. The holoenzyme telomerase rebuilds telomeres and is
      composed of two components, the catalytic protein telomerase reverse
      transcriptase (TERT) and the telomerase RNA (TERC). TERC is ubiquitously
      expressed in somatic cells and is thought to have no regulatory effects on
      telomerase activity. Transgenic expression of human TERT (hTERT) in bovine
      somatic and embryonic cells extends telomere length and enhances telomerase
      activity. To obtain further insight into the regulatory capacity of the two
      telomerase components, we have studied the ability of hTERC and hTERT to increase
      telomerase activity and telomere length in bovine embryos. Expression plasmids
      for the human RNA component (hTERC) and/or the catalytic subunit of human
      telomerase (hTERT), respectively, were injected into the cytoplasm of in vitro
      produced bovine zygotes. Ectopic expression of hTERC increased telomerase
      activity and telomere length in bovine blastocysts. Coexpression of hTERT and
      hTERC did not result in further telomere elongation when compared to the hTERC
      group. These data indicate that TERC is one of the limiting factors of telomerase
      activity in bovine blastocysts, and further establish bovine preimplantation
      embryos as a useful model to modulate telomere length with impact for basic
      embryology and derivation of pluripotent cells.

PMID- 22855561
TI  - Fluorescent intercalator displacement replacement (FIDR) assay: determination of
      relative thermodynamic and kinetic parameters in triplex formation--a case study
      using triplex-forming LNAs.
AB  - Triplex forming oligonucleotides (TFOs) are the most commonly used approach for
      site-specific targeting of double stranded DNA (dsDNA). Important parameters
      describing triplex formation include equilibrium binding constants (K(eq)) and
      association/dissociation rate constants (k(on) and k(off)). The 'fluorescent
      intercalator displacement replacement' (FIDR) assay is introduced herein as an
      operationally simple approach toward determination of these parameters for
      triplexes involving TC-motif TFOs. Briefly described, relative rate constants are
      determined from fluorescence intensity changes upon: (i) TFO-mediated
      displacement of pre-intercalated and fluorescent ethidium from dsDNA targets
      (triplex association) and (ii) Watson-Crick complement-mediated displacement of
      the TFO and replacement with ethidium (triplex dissociation). The assay is used
      to characterize triplexes between purine-rich dsDNA targets and TC-motif TFOs
      modified with six different locked nucleic acid (LNA) monomers, i.e. conventional
      and C5-alkynyl-functionalized LNA and alpha-L-LNA pyrimidine monomers. All of the
      studied monomers increase triplex stability by decreasing the triplex
      dissociation rate. LNA-modified TFOs form more stable triplexes than alpha-L-LNA
      modified counterparts owing to slower triplex dissociation. Triplexes modified
      with C5-(3-aminopropyn-1-yl)-LNA-U monomer Z are particularly stable. The study
      demonstrates that three affinity-enhancing features can be combined into one high
      affinity TFO monomer: conformational restriction of the sugar ring, expansion of
      the pyrimidine pi-stacking surface and introduction of an exocyclic amine.

PMID- 22855563
TI  - Effects of slow freezing procedure on late blastocyst gene expression and
      survival rate in rabbit.
AB  - Studies of embryo cryopreservation efficiency have focused mainly on technical
      and embryo factors. To determine how a slow freezing process affects embryo and
      fetal development, we studied in vivo development ability after the freezing
      procedure by assessing blastocyst development at Day 6, implantation, and birth
      rates. A transcriptional microarray study was also performed to compare gene
      expression of 6-day-old rabbit embryos previously frozen and transferred into
      recipient rabbit females to their in vivo counterparts. Our goal was to study
      which alteration caused by the freezing procedure still remained in late
      blastocyst stage just at the time when the implantation process began. A
      microarray specifically designed to study rabbit gene expression profiling was
      used in this study. Lower implantation and birth rates were obtained in frozen
      embryos than in the control group (29.9% and 25.7% vs 88.5% and 70.8% for frozen
      and control embryos, respectively). Likewise, differences were also observed in
      gene expression profiles. Compared to 6-day-old in vivo-derived embryos, viable
      frozen embryos presented 70 differentially expressed genes, 24 upregulated and 46
      downregulated. In conclusion, our findings showed that the slow freezing process
      affected late blastocyst development, implantation, and birth rates and that the
      gene expression alterations identified at late blastocyst stage could be useful
      in understanding the differences in developmental potential observed and the
      deficiencies that might hinder implantation and fetal development.

PMID- 22855565
TI  - Lineage tree for the venous pole of the heart: clonal analysis clarifies
      controversial genealogy based on genetic tracing.
AB  - RATIONALE: Genetic tracing experiments and cell lineage analyses are
      complementary approaches that give information about the progenitor cells of a
      tissue. Approaches based on gene expression have led to conflicting views about
      the origin of the venous pole of the heart. Whereas the heart forms from 2
      sources of progenitor cells, the first and second heart fields, genetic tracing
      has suggested a distinct origin for caval vein myocardium, from a proposed third
      heart field. OBJECTIVE: To determine the cell lineage history of the myocardium
      at the venous pole of the heart. METHODS AND RESULTS: We used retrospective
      clonal analyses to investigate lineage segregation for myocardium at the venous
      pole of the mouse heart, independent of gene expression. CONCLUSIONS: Our lineage
      analysis unequivocally shows that caval vein and atrial myocardium share a common
      origin and demonstrates a clonal relationship between the pulmonary vein and
      progenitors of the left venous pole. Clonal characteristics give insight into the
      development of the veins. Unexpectedly, we found a lineage relationship between
      the venous pole and part of the arterial pole, which is derived exclusively from
      the second heart field. Integration of results from genetic tracing into the
      lineage tree adds a further temporal dimension to this reconstruction of the
      history of venous myocardium and the arterial pole.

PMID- 22855566
TI  - Vitamin D and depression: is there a relationship in young women?
AB  - BACKGROUND: Depression is emerging as a leading cause of morbidity and mortality
      in young adults. New biological assessment strategies such as biological markers
      are needed to more accurately assess for depression in this age group. Vitamin D
      may present such an opportunity. OBJECTIVE: A descriptive correlational design
      with convenience sampling was used to address the research question: Is there a
      relationship between vitamin D serum levels and depression scores in young adult
      women? DESIGN: One hundred thirty-nine participants completed a health
      questionnaire, Beck Depression Inventory, and had serum vitamin D, 25(OH)D,
      levels drawn. RESULTS: No statistically significant correlation between vitamin D
      level and depression was identified. Statistically significant differences
      between African American and Caucasian women were detected on vitamin D levels
      but not on the Beck Depression Inventory. CONCLUSION: Based on the results of
      this study, vitamin D cannot be used as a biomarker for depression in women aged
      18 to 24 years. Clinical implications of no relationship between vitamin D and
      depression will be explored and the cut-point for serum 25(OH)D levels will be
      discussed.

PMID- 22855567
TI  - An assessment of students' confidence in performing psychiatric mental health
      nursing skills: the impact of the clinical practicum experience.
AB  - BACKGROUND: In 2008, the American Psychiatric Nurses Association and the
      International Society for Psychiatric Nursing jointed developed Psychiatric
      Mental Health Nursing competencies for BSN students. In the newly created
      accelerated track of the BSN program, students spend less time than traditional
      students in psychiatric mental health (PMH) clinical practica. OBJECTIVES: The
      primary objective was to discover how the PMH practicum experience influences BSN
      students' perceptions of their confidence in performing PMH clinical skills.
      DESIGN: An evaluation design was used in this study. RESULTS: There was
      significant improvement in students' confidence performing PMH clinical
      competencies after completing the PMH nursing practicum. The current structure of
      clinical provides students with experiences that promote their confidence.
      CONCLUSIONS: Students self-assessment about learning needs and skill level should
      be assessed preclinically to allow for practice to gain confidence.

PMID- 22855568
TI  - APNA: demystifying our mission.

PMID- 22855571
TI  - Large ventral lateral neurons determine the phase of evening activity peak across
      photoperiods in Drosophila melanogaster.
AB  - The dual-oscillator model, originally proposed as a mechanism for how vertebrates
      adapt to seasonal changes, has been invoked to explain circadian entrainment in
      Drosophila melanogaster. Distinct subsets of neurons have been designated as
      "morning" and "evening" oscillators that function as regulators of rhythmic
      activity/rest behavior. Some studies have led to a model in which a subset of 8
      "morning" cells (4 bilaterally located small ventral lateral neurons) and another
      subset of approximately 130 "evening" cells exert different levels of dominance
      within the circadian circuit in different seasons. However, many studies propose
      a more integrative neuronal network, with the whole network orchestrating
      activity/rest rhythms in different seasons, as opposed to hierarchical dominance
      among neurons. Within the circadian network, our understanding of the role of the
      large ventral lateral neurons (l-LN(v)) has thus far been limited to conveying
      light information to the clocks and as light-activated neurons mediating arousal.
      In support of the framework of a more distributed model, we report an important
      circadian clock-related role for the l-LN(v) in electrical activity-dependent
      phasing of the evening peak across a range of photoperiods. Further, we propose a
      model in which l-LN(v) enable adaptation to seasonal changes by regulating the
      phase of the evening peak. Additionally, we demonstrate a hitherto unknown role
      for the small ventral lateral neurons (s-LN(v)) in the arousal circuit, thus
      showing that neuronal function is flexible such that certain neurons can play
      more than one role in distinct circuits.

PMID- 22855569
TI  - Improvement in coronary blood flow velocity with acute biventricular pacing is
      predominantly due to an increase in a diastolic backward-travelling decompression
      (suction) wave.
AB  - BACKGROUND: Normal coronary blood flow is principally determined by a backward
      traveling decompression (suction) wave in diastole. Dyssynchronous chronic heart
      failure may attenuate suction, because regional relaxation and contraction
      overlap in timing. We hypothesized that biventricular pacing, by restoring left
      ventricular (LV) synchronization and improving LV relaxation, might increase this
      suction wave, improving coronary flow. METHOD AND RESULTS: Ten patients with
      chronic heart failure (9 males; age 65+/-12; ejection fraction 26+/-7%) with left
      bundle-branch block (LBBB; QRS duration 174+/-18 ms) were atriobiventricularly
      paced at 100 bpm. LV pressure was measured and wave intensity calculated from
      invasive coronary flow velocity and pressure, with native conduction (LBBB) and
      during biventricular pacing at atrioventricular (AV) delays of 40 ms, 120 ms, and
      separately preidentified hemodynamically optimal AV delay. In comparison with
      LBBB, biventricular pacing at separately preidentified hemodynamically optimal AV
      delay (BiV-Opt) enhanced coronary flow velocity time integral by 15% (7%-25%)
      (P=0.007), LV dP/dt(max) by 15% (10%-21%) (P=0.005), and (neg)dP/dt(max) by 17%
      (9%-22%) (P=0.005). The cumulative intensity of the diastolic backward
      decompression (suction) wave increased by 26% (18%-54%) (P=0.005). The majority
      of the increase in coronary flow velocity time integral occurred in diastole (69%
      [41%-84% ]; P=0.047). The systolic compression waves also increased: forward by
      36% (6%-49%) (P=0.022) and backward by 38% (20%-55%) (P=0.022). Biventricular
      pacing at AV delays of 120 ms generated a smaller LV dP/dt(max) (by 12% [5%-23%
      ], P=0.013) and (neg)dP/dt(max) (by 15% [8%-40% ]; P=0.009) increase than BiV
      Opt, against LBBB as reference; BiV-Opt and biventricular pacing at AV delays of
      120 ms were not significantly different in coronary flow velocity time integral
      or waves. Biventricular pacing at AV delays of 40 ms was no different from LBBB.
      CONCLUSIONS: When biventricular pacing improves LV contraction and relaxation, it
      increases coronary blood flow velocity, predominantly by increasing the dominant
      diastolic backward decompression (suction) wave.

PMID- 22855570
TI  - Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor
      gamma deletion in smooth muscle cells impairs intravascular thermoregulation and
      enhances atherosclerosis.
AB  - BACKGROUND: Perivascular adipose tissue (PVAT) surrounds most vessels and shares
      common features with brown adipose tissue (BAT). Although adaptive thermogenesis
      in BAT increases energy expenditure and is beneficial for metabolic diseases,
      little is known about the role of PVAT in vascular diseases such as
      atherosclerosis. We hypothesize that the thermogenic function of PVAT regulates
      intravascular temperature and reduces atherosclerosis. METHODS AND RESULTS: PVAT
      shares similar structural and proteomics with BAT. We demonstrated that PVAT has
      thermogenic properties similar to BAT in response to cold stimuli in vivo.
      Proteomics analysis of the PVAT from mice housed in a cold environment identified
      differential expression in proteins highly related to cellular metabolic
      processes. In a mouse model deficient in peroxisome proliferator-activated
      receptor-gamma in smooth muscle cells (SMPG KO mice), we uncovered a complete
      absence of PVAT surrounding the vasculature, likely caused by peroxisome
      proliferator-activated receptor-gamma deletion in the perivascular adipocyte
      precursor cells as well. Lack of PVAT, which results in loss of its thermogenic
      activity, impaired vascular homeostasis, which caused temperature loss and
      endothelial dysfunction. We further showed that cold exposure inhibits
      atherosclerosis and improves endothelial function in mice with intact PVAT but
      not in SMPG KO mice as a result of impaired lipid clearance. Proinflammatory
      cytokine expression in PVAT is not altered on exposure to cold. Finally,
      prostacyclin released from PVAT contributes to the vascular protection against
      endothelial dysfunction. CONCLUSIONS: PVAT is a vasoactive organ with functional
      characteristics similar to BAT and is essential for intravascular
      thermoregulation of cold acclimation. This thermogenic capacity of PVAT plays an
      important protective role in the pathogenesis of atherosclerosis.

PMID- 22855572
TI  - Adult emergence rhythm of fruit flies Drosophila melanogaster under seminatural
      conditions.
AB  - In insects, the role of circadian clocks in the temporal regulation of adult
      emergence rhythm under natural conditions has not previously been reported. Here
      we present the results of a study aimed at examining the time course and waveform
      of emergence rhythm in the fruit fly Drosophila melanogaster under seminatural
      condition (SN). We studied this rhythm in wild-type and clock mutant flies under
      SN in parallel with laboratory condition (LAB) to examine (1) how the rhythm
      differs between SN and LAB, (2) what roles the circadian clock protein PERIOD and
      the circadian photoreceptor CRYPTOCHROME (CRY) play in the regulation of
      emergence rhythm under SN, and (3) whether there is seasonality in the rhythm.
      Under SN, wild-type flies displayed tightly gated emergence, peaking at "dawn"
      and gradually tapering down toward the evening, with little or no emergence by
      night, while in LAB, flies emerged throughout the light phase of light-dark (LD)
      cycles. The period loss-of-function mutant (per ( 0 )) flies were arrhythmic in
      LAB but displayed weak rhythmic emergence under SN. Under SN, cry mutants
      displayed less robust rhythm with wider gates, greater variance in peak timing,
      and enhanced nighttime emergence compared to controls. Furthermore, flies showed
      seasonal variation in emergence rhythm, coupled either to light or to
      humidity/temperature depending on the severity of environmental conditions. These
      results suggest that adult emergence rhythm of Drosophila is more robust in
      nature, is coupled to environmental cycles, and shows seasonal variations.

PMID- 22855573
TI  - Dissociation of ultradian and circadian phenotypes in female and male Siberian
      hamsters.
AB  - Three experiments addressed whether pronounced alterations in the circadian
      system yielded concomitant changes in ultradian timing. Female Siberian hamsters
      were housed in a 16L:8D photoperiod after being subjected to a disruptive phase
      shifting protocol that produced 3 distinct permanent circadian phenotypes: some
      hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal
      locomotor activity (ENTR), others displayed free-running CRs (FR), and a third
      cohort was circadian arrhythmic (ARR). The period of the ultradian locomotor
      rhythm (UR) did not differ among the 3 circadian phenotypes; neuroendocrine
      generation of URs remains viable in the absence of coherent circadian
      organization and appears to be mediated by substrates functionally and
      anatomically distinct from those that generate CRs. Pronounced light-dark
      differences in several UR characteristics in ENTR hamsters were completely absent
      in circadian arrhythmic hamsters. The disruptive phase-shifting protocol may
      compromise direct visual input to ultradian oscillators but more likely
      indirectly affects URs by interrupting visual afference to the circadian system.
      Additional experiments documented that deuterium oxide and constant light, each
      of which substantially lengthened the period of free-running CRs, failed to
      change the period of concurrently monitored URs. The resistance of URs to
      deuteration contrasts with the slowing of virtually all other biological timing
      processes, including CRs. Considered together, the present results point to the
      existence of separable control mechanisms for generation of circadian and
      ultradian rhythms.

PMID- 22855574
TI  - Acute behavioral responses to light and darkness in nocturnal Mus musculus and
      diurnal Arvicanthis niloticus.
AB  - The term masking refers to immediate responses to stimuli that override the
      influence of the circadian timekeeping system on behavior and physiology. Masking
      by light and darkness plays an important role in shaping an organism's daily
      pattern of activity. Nocturnal animals generally become more active in response
      to darkness (positive masking) and less active in response to light (negative
      masking), and diurnal animals generally have opposite patterns of response. These
      responses can vary as a function of light intensity as well as time of day. Few
      studies have directly compared masking in diurnal and nocturnal species, and none
      have compared rhythms in masking behavior of diurnal and nocturnal species. Here,
      we assessed masking in nocturnal mice (Mus musculus) and diurnal grass rats
      (Arvicanthis niloticus). In the first experiment, animals were housed in a 12:12
      light-dark (LD) cycle, with dark or light pulses presented at 6 Zeitgeber times
      (ZTs; with ZT0 = lights on). Light pulses during the dark phase produced negative
      masking in nocturnal mice but only at ZT14, whereas light pulses resulted in
      positive masking in diurnal grass rats across the dark phase. In both species,
      dark pulses had no effect on behavior. In the 2nd experiment, animals were kept
      in constant darkness or constant light and were presented with light or dark
      pulses, respectively, at 6 circadian times (CTs). CT0 corresponded to ZT0 of the
      preceding LD cycle. Rhythms in masking responses to light differed between
      species; responses were evident at all CTs in grass rats but only at CT14 in
      mice. Responses to darkness were observed only in mice, in which there was a
      significant increase in activity at CT 22. In the 3rd experiment, animals were
      kept on a 3.5:3.5-h LD cycle. Surprisingly, masking was evident only in grass
      rats. In mice, levels of activity during the light and dark phases of the 7-h
      cycle did not differ, even though the same animals had responded to discrete
      photic stimuli in the first 2 experiments. The results of the 3 experiments are
      discussed in terms of their methodological implications and for the insight they
      offer into the mechanisms and evolution of diurnality.

PMID- 22855575
TI  - Photic sensitivity for circadian response to light varies with photoperiod.
AB  - The response of the circadian system to light varies markedly depending on photic
      history. Under short day lengths, hamsters exhibit larger maximal light-induced
      phase shifts as compared with those under longer photoperiods. However, effects
      of photoperiod length on sensitivity to subsaturating light remain unknown. Here,
      Syrian hamsters were entrained to long or short photoperiods and subsequently
      exposed to a 15-min light pulse across a range of irradiances (0-68.03 uW/cm(2))
      to phase shift activity rhythms. Phase advances exhibited a dose response, with
      increasing irradiances eliciting greater phase resetting in both conditions.
      Photic sensitivity, as measured by the half-saturation constant, was increased 40
      fold in the short photoperiod condition. In addition, irradiances that generated
      similar phase advances under short and long days produced equivalent phase
      delays, and equal photon doses produced larger delays in the short photoperiod
      condition. Mechanistically, equivalent light exposure induced greater pERK, PER1,
      and cFOS immunoreactivity in the suprachiasmatic nuclei of animals under shorter
      days. Patterns of immunoreactivity in all 3 proteins were related to the size of
      the phase shift rather than the intensity of the photic stimulus, suggesting that
      photoperiod modulation of light sensitivity lies upstream of these events within
      the signal transduction cascade. This modulation of light sensitivity by
      photoperiod means that considerably less light is necessary to elicit a circadian
      response under the relatively shorter days of winter, extending upon the known
      seasonal changes in sensitivity of sensory systems. Further characterizing the
      mechanisms by which photoperiod alters photic response may provide a potent tool
      for optimizing light treatment for circadian and affective disorders in humans.

PMID- 22855576
TI  - Dim nighttime light impairs cognition and provokes depressive-like responses in a
      diurnal rodent.
AB  - Circadian disruption is a common by-product of modern life. Although jet lag and
      shift work are well-documented challenges to circadian organization, many more
      subtle environmental changes cause circadian disruption. For example, frequent
      fluctuations in the timing of the sleep/wake schedule, as well as exposure to
      nighttime lighting, likely affect the circadian system. Most studies of these
      effects have focused on nocturnal rodents, which are very different from diurnal
      species with respect to their patterns of light exposure and the effects that
      light can have on their activity. Thus, the authors investigated the effect of
      nighttime light on behavior and the brain of a diurnal rodent, the Nile grass
      rat. Following 3 weeks of exposure to standard light/dark (LD; 14:10 light [~150
      lux] /dark [0 lux]) or dim light at night (dLAN; 14:10 light [~150 lux] /dim [5
      lux]), rats underwent behavioral testing, and hippocampal neurons within CA1,
      CA3, and the dentate gyrus (DG) were examined. Three behavioral effects of dLAN
      were observed: (1) decreased preference for a sucrose solution, (2) increased
      latency to float in a forced swim test, and (3) impaired learning and memory in
      the Barnes maze. Light at night also reduced dendritic length in DG and basilar
      CA1 dendrites. Dendritic length in the DG positively correlated with sucrose
      consumption in the sucrose anhedonia task. Nighttime light exposure did not
      disrupt the pattern of circadian locomotor activity, and all grass rats
      maintained a diurnal activity pattern. Together, these data suggest that exposure
      to dLAN can alter affective responses and impair cognition in a diurnal animal.

PMID- 22855577
TI  - The Input Signal Step Function (ISSF), a standard method to encode input signals
      in SBML models with software support, applied to circadian clock models.
AB  - Time-dependent light input is an important feature of computational models of the
      circadian clock. However, publicly available models encoded in standard
      representations such as the Systems Biology Markup Language (SBML) either do not
      encode this input or use different mechanisms to do so, which hinders
      reproducibility of published results as well as model reuse. The authors describe
      here a numerically continuous function suitable for use in SBML for models of
      circadian rhythms forced by periodic light-dark cycles. The Input Signal Step
      Function (ISSF) is broadly applicable to encoding experimental manipulations,
      such as drug treatments, temperature changes, or inducible transgene expression,
      which may be transient, periodic, or mixed. It is highly configurable and is able
      to reproduce a wide range of waveforms. The authors have implemented this
      function in SBML and demonstrated its ability to modify the behavior of publicly
      available models to accurately reproduce published results. The implementation of
      ISSF allows standard simulation software to reproduce specialized circadian
      protocols, such as the phase-response curve. To facilitate the reuse of this
      function in public models, the authors have developed software to configure its
      behavior without any specialist knowledge of SBML. A community-standard approach
      to represent the inputs that entrain circadian clock models could particularly
      facilitate research in chronobiology.

PMID- 22855578
TI  - Learning chronobiology by improving Wikipedia.
AB  - Although chronobiology is of growing interest to scientists, physicians, and the
      general public, access to recent discoveries and historical perspectives is
      limited. Wikipedia is an online, user-written encyclopedia that could enhance
      public access to current understanding in chronobiology. However, Wikipedia is
      lacking important information and is not universally trusted. Here, 46 students
      in a university course edited Wikipedia to enhance public access to important
      discoveries in chronobiology. Students worked for an average of 9 h each to
      evaluate the primary literature and available Wikipedia information, nominated
      sites for editing, and, after voting, edited the 15 Wikipedia pages they
      determined to be highest priorities. This assignment
      (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to
      implement, required relatively short time commitments from the professor and
      students, and had measurable impacts on Wikipedia and the students. Students
      created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer
      reviewed articles. The targeted sites all became top hits in online search
      engines. Because their writing was and will be read by a worldwide audience,
      students found the experience rewarding. Students reported significantly
      increased comfort with reading, critiquing, and summarizing primary literature
      and benefited from seeing their work edited by other scientists and editors of
      Wikipedia. We conclude that, in a short project, students can assist in making
      chronobiology widely accessible and learn from the editorial process.

PMID- 22855580
TI  - The relationship between homologous recombination repair and the sensitivity of
      human epidermis to the size of daily doses over a 5-week course of breast
      radiotherapy.
AB  - PURPOSE: A molecular understanding of tissue sensitivity to radiotherapy fraction
      size is missing. Here, we test the hypothesis that sensitivity to fraction size
      is influenced by the DNA repair system activated in response to DNA double-strand
      breaks (DSB). Human epidermis was used as a model in which proliferation and DNA
      repair were correlated over 5 weeks of radiotherapy. EXPERIMENTAL DESIGN:
      Radiotherapy (25 fractions of 2 Gy) was prescribed to the breast in 30 women with
      early breast cancer. Breast skin biopsies were collected 2 hours after the 1st
      and 25th fractions. Samples of contralateral breast skin served as controls.
      Sections were coimmunostained for Ki67, cyclin A, p21, RAD51, 53BP1, and beta1
      integrin. RESULTS: After 5 weeks of radiotherapy, the mean basal Ki67 density
      increased from 5.72 to 15.46 cells per millimeter of basement membrane (P =
      0.002), of which the majority were in S/G2 phase, as judged by cyclin A staining
      (P < 0.0003). The p21 index rose from 2.8% to 87.4% (P < 0.0001) after 25
      fractions, indicating cell cycle arrest. By week 5, there was a 4-fold increase
      (P = 0.0003) in the proportion of Ki67-positive cells showing RAD51 foci,
      suggesting increasing activation of homologous recombination. CONCLUSIONS: Cell
      cycle arrest in S/G2 phase in the basal epidermis after a 5-week course of
      radiotherapy is associated with greater use of homologous recombination for
      repairing DSB. The high fidelity of homologous recombination, which is
      independent of DNA damage levels, may explain the low-fractionation sensitivity
      of tissues with high-proliferative indices, including self-renewing normal
      tissues and many cancers.

PMID- 22855579
TI  - Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low
      expression of the glucocorticoid receptor gene NR3C1.
AB  - PURPOSE: Because dexamethasone remains a key component of myeloma therapy, we
      wished to examine the impact of baseline and relapse expression levels of the
      glucocorticoid receptor gene NR3C1 on survival outcomes in the context of
      treatment with or without thalidomide. EXPERIMENTAL DESIGN: We investigated the
      clinical impact of gene expression profiling (GEP)-derived expression levels of
      NR3C1 in 351 patients with GEP data available at baseline and in 130 with data
      available at relapse, among 668 subjects accrued to total therapy 2 (TT2).
      RESULTS: Low NR3C1 expression levels had a negative impact on progression-free
      survival (PFS; HR, 1.47; P = 0.030) and overall survival (OS; HR, 1.90; P =
      0.002) in the no-thalidomide arm. Conversely, there was a significant clinical
      benefit of thalidomide for patients with low receptor levels (OS: HR, 0.54; P =
      0.015; PFS: HR, 0.54; P = 0.004), mediated most likely by thalidomide's
      upregulation of NR3C1. In the context of both baseline and relapse parameters,
      post-relapse survival (PRS) was adversely affected by low NR3C1 levels at relapse
      in a multivariate analysis (HR, 2.61; P = 0.012). CONCLUSION: These findings
      justify the inclusion of NR3C1 expression data in the work-up of patients with
      myeloma as it can significantly influence the choice of therapy and, ultimately,
      OS. The identification of an interaction term between thalidomide and NR3C1
      underscores the importance of pharmacogenomic studies in the systematic study of
      new drugs.

PMID- 22855582
TI  - Introduction and guide to the special issue on economic and workforce issues
      facing dentistry and dental education in the twenty-first century.

PMID- 22855581
TI  - Contrasted outcomes to gefitinib on tumoral IGF1R expression in head and neck
      cancer patients receiving postoperative chemoradiation (GORTEC trial 2004-02).
AB  - PURPOSE: Intermediate/high-risk operated patients with head and neck cancer may
      benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to
      chemoradiation. This study was designed to assess improved outcomes and identify
      predictive biomarkers. EXPERIMENTAL DESIGN: Patients provided informed consent
      for tumor biomarker analyses and, when eligible, were further enrolled in the
      therapeutic CARISSA multicenter randomized phase II trial of postoperative
      irradiation with cisplatin + gefitinib (GORTEC 2004-02-NCT00169221). RESULTS:
      Seventy-nine patients were included in the biomarker study, whereas 27 did not
      meet prerequisites for randomization between gefitinib and placebo. Two-year
      disease-free survival (DFS) rate was 65.0% and did not differ between randomized
      patients treated with gefitinib or placebo (P = 0.85). The similarity of DFS
      curves between nonrandomized patients (n = 27), randomized patients without
      gefitinib (n = 27), and randomized patients receiving gefitinib (n = 25), and
      similar histoclinical parameter distributions for all groups, allowed us to
      conduct statistical analyses on the entire population. On multivariate analysis,
      elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like
      growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly
      associated with shorter DFS. There was a significant interaction between IGF1R
      and gefitinib. Gefitinib abolished the prognostic discriminative power of high
      IGF1R expression; patients with elevated IGF1R expression benefited from
      gefitinib whereas those with low IGF1R fared worse. CONCLUSION: Gefitinib
      treatment affords no significant clinical benefit on DFS in an unselected
      population of patients with head and neck cancer. Our results point to the
      potential advantage of personalizing treatment for gefitinib based on tumoral
      IGF1R expression. This should foster confirmatory analyses in trials involving
      EGFR-targeting agents.

PMID- 22855583
TI  - The market for dental services.

PMID- 22855584
TI  - The structure and economics of dental education.

PMID- 22855585
TI  - Factors influencing demand for dental services: population, demographics,
      disease, insurance.

PMID- 22855586
TI  - National trends in economic data for dental services and dental education.

PMID- 22855587
TI  - Recent trends in the utilization of dental care in the United States.
AB  - The authors examined trends in the utilization of oral health services in the
      United States from 1997 to 2010, including breakdowns by age and poverty level.
      They examined trends in one major driver of utilization: insurance coverage. The
      results suggest that the recent economic downturn did not result in an overall
      decrease in the utilization of dental services. Rather, the findings suggest an
      earlier decline from 2003 to 2008. In this article, the authors report that the
      overall trend masked significant variation by age and poverty level. Among
      children, there was steady growth in utilization from 1997 to 2010. This appears
      to have coincided with a shift away from private insurance toward public coverage
      and a significant drop in the percentage of uninsured children. Among non-elderly
      adults, however, utilization has been falling steadily since 1997 among all but
      the wealthiest income group. During the great recession from December 2007 to
      June 2009, the decline in utilization accelerated among those in the lowest
      income group. The decrease in adult utilization appears related to a decrease in
      private insurance coverage and an increase in public coverage and noninsured
      rates. As a consequence of these trends in coverage, the authors predict a
      continued decline in the utilization of dental services among non-elderly adults.

PMID- 22855588
TI  - The past and future evolution of the dental workforce team.
AB  - This article looks at changes in the number and mix of providers in the dental
      workforce over the past sixty years. First, enrollment trends in dental education
      programs are investigated. These educational programs feed directly into the
      dental workforce. Then, the changes in the dental workforce are examined. The
      focus of this investigation is the composition of the dental workforce and how
      the components of the workforce have changed over time. The forces that are
      responsible for these changes in the workforce are explored next. Finally, the
      possibility for workforce changes in the future is considered.

PMID- 22855589
TI  - Evolving trends in size and structure of group dental practices in the United
      States.
AB  - In this study, the authors examined recent trends in the growth of dental
      establishments and dental firms, including geographic location. In this article,
      they also present information about the demographic characteristics of dentists
      who work in a dental practice that is part of a larger company that delivers
      dental care in multiple locations. The number of dental establishments (single
      locations) and the average size of these establishments grew from 1992 to 2007.
      Large multi-unit dental firms grew in terms of number of establishments and the
      percentage of total receipts. Large multi-unit dental firms represent a small but
      growing segment of the dental market. Dentists less than thirty-five years old
      were most likely to work in a practice that was part of a larger company, and
      females were more likely than males to work in such a setting. The percentage of
      dentists working in these settings was also found to vary by region and state.
      The authors present a typology of dental group practice and suggest that future
      research should take into account the differences so that appropriate conclusions
      can be drawn and generalizations across categories are not made.

PMID- 22855590
TI  - Economic impact of dental hygienists on solo dental practices.
AB  - The fact that a significant percentage of dentists employ dental hygienists
      raises an important question: Are dental practices that utilize a dental
      hygienist structurally and operationally different from practices that do not?
      This article explores differences among dental practices that operate with and
      without dental hygienists. Using data from the American Dental Association's 2003
      Survey of Dental Practice, a random sample survey of U.S. dentists, descriptive
      statistics were used to compare selected characteristics of solo general
      practitioners with and without dental hygienists. Multivariate regression
      analysis was used to estimate the effect of dental hygienists on the gross
      billings and net incomes of solo general practitioners. Differences in practice
      characteristics--such as hours spent in the practice and hours spent treating
      patients, wait time for a recall visit, number of operatories, square feet of
      office space, net income, and gross billings--were found between solo general
      practitioners who had dental hygienists and those who did not. Solo general
      practitioners with dental hygienists had higher gross billings. Higher gross
      billings would be expected, as would higher expenses. However, net incomes of
      those with dental hygienists were also higher. In contrast, the mean waiting time
      for a recall visit was higher among dentists who employed dental hygienists.
      Depending on personal preferences, availability of qualified personnel, etc.,
      dentists who do not employ dental hygienists but have been contemplating that
      path may want to further research the benefits and opportunities that may be
      realized.

PMID- 22855591
TI  - Expanded function allied dental personnel and dental practice productivity and
      efficiency.
AB  - This study examined the impact of expanded function allied dental personnel on
      the productivity and efficiency of general dental practices. Detailed practice
      financial and clinical data were obtained from a convenience sample of 154
      general dental practices in Colorado. In this state, expanded function dental
      assistants can provide a wide range of reversible dental services/procedures, and
      dental hygienists can give local anesthesia. The survey identified practices that
      currently use expanded function allied dental personnel and the specific
      services/procedures delegated. Practice productivity was measured using patient
      visits, gross billings, and net income. Practice efficiency was assessed using a
      multivariate linear program, Data Envelopment Analysis. Sixty-four percent of the
      practices were found to use expanded function allied dental personnel, and on
      average they delegated 31.4 percent of delegatable services/procedures. Practices
      that used expanded function allied dental personnel treated more patients and had
      higher gross billings and net incomes than those practices that did not; the more
      services they delegated, the higher was the practice's productivity and
      efficiency. The effective use of expanded function allied dental personnel has
      the potential to substantially expand the capacity of general dental practices to
      treat more patients and to generate higher incomes for dental practices.

PMID- 22855592
TI  - Impact of dental therapists on productivity and finances: I. Literature review.
AB  - This study examined the financial impact of dental therapists on Federally
      Qualified Health Center dental clinics (treating children) and on private general
      dental practices (treating children and adults). This article, the first of four
      on this subject, reviews the dental therapy literature and the dental access
      problem for low-income children. Dental therapists now practice in many developed
      countries, tribal areas of Alaska, and Minnesota. These allied dental
      professionals vary in their training and required dentist supervision, but all
      provide routine restorative and other related services to children and adults.
      The limited literature on the impact of dental therapists suggests that they work
      mainly in school and community clinics and some private practices, are well
      accepted by patients, provide restorations that are comparable in quality to
      those of dentists, expand the supply of services, do not increase private
      practices' net revenues, and in school programs decrease the number of untreated
      decayed teeth. Of the approximately 33.8 million children enrolled in Medicaid
      and the Children's Health Insurance Program (CHIP), some 40 percent now receive
      at least one annual dental visit. To increase utilization for all children to 60
      percent--the rate seen in children from upper-income families--another 6.7
      million children need to receive care; dental therapists may help to accomplish
      that objective.

PMID- 22855593
TI  - Impact of dental therapists on productivity and finances: II. Federally Qualified
      Health Centers.
AB  - This article estimates the impact of dental therapists treating children on
      Federally Qualified Health Center (FQHC) dental clinic finances and productivity.
      The analysis is based on twelve months of patient visit and financial data from
      large FQHC dental clinics (multiple delivery sites) in Connecticut and Wisconsin.
      Assuming dental therapists provide restorative, extraction, and pulpal services
      and dental hygienists continue to deliver all hygiene services, the maximum
      reduction in costs is about 6 percent. The limited impact of dental therapists on
      FQHC dental clinic finances is because 1) dental therapists only account for 17
      percent of children services and 2) dentists are responsible for only 25 percent
      of clinic expenses and cost reductions are related to the difference between
      dental therapist and dentist wage rates.

PMID- 22855594
TI  - Impact of dental therapists on productivity and finances: III. FQHC-run, school
      based dental care programs in Connecticut.
AB  - In many developed countries, the primary role of dental therapists is to care for
      children in school clinics. This article describes Federally Qualified Health
      Center (FQHC)-run, school-based dental programs in Connecticut and explores the
      theoretical financial impact of substituting dental therapists for dentists in
      these programs. In schools, dental hygienists screen children and provide
      preventive services, using portable equipment and temporary space. Children
      needing dentist services are referred to FQHC clinics or to FQHC-employed
      dentists who provide care in schools. The primary findings of this study are that
      school-based programs have considerable potential to reduce access disparities
      and the estimated reduction in per patient costs approaches 50 percent versus
      providing care in FQHC dental clinics. In terms of substituting dental therapists
      for dentists, the estimated additional financial savings was found to be about 5
      percent. Nationally, FQHC-operated, school-based dental programs have the
      potential to increase Medicaid/CHIP utilization from the current 40 percent to 60
      percent for a relatively modest increase in total expenditures.

PMID- 22855595
TI  - Dental therapists in general dental practices: an economic evaluation.
AB  - Dental access disparities are well documented and have been recognized as a
      national problem. Their major cause is the lack of reasonable Medicaid
      reimbursement rates for the underserved. Specifically, Medicaid reimbursement
      rates for children average 40 percent below market rates. In addition, most state
      Medicaid programs do not cover adults. To address these issues, advocates of
      better oral health for the underserved are considering support for a new allied
      provider--a dental therapist--capable of providing services at a lower cost per
      service and in low-income and rural areas. Using a standard economic analysis,
      this study estimated the potential cost, price, utilization, and dentist's income
      effects of dental therapists employed in general dental practices. The analysis
      is based on national general dental practice data and the broadest scope of
      responsibility for dental therapists that their advocates have advanced,
      including the ability to provide restorations and extractions to adults and
      children, training for three years, and minimum supervision. Assuming dental
      therapists provide restorative, extraction, and pulpal services to patients of
      all ages and dental hygienists continue to deliver all hygiene services, the mean
      reduction in a general practice costs ranges between 1.57 and 2.36 percent. For
      dental therapists treating children only, the range is 0.31 to 0.47 percent. The
      effects on price and utilization are even smaller. In addition, the effects on
      most dentists' gross income, hours of work, and net income are negative. The
      estimated economic impact of dental therapists in the United States on private
      dental practice is very limited; therefore, the demand for dental therapists by
      private practices also would probably be very limited.

PMID- 22855596
TI  - Influence of private practice employment of dental therapists in Saskatchewan on
      the future supply of dental therapists in Canada.
AB  - The profession of dental therapy has long been held up as a model for reducing
      access to care barriers in high-risk, underserved populations worldwide. Dental
      therapists practice in many countries delivering preventive and basic restorative
      care to children and adults. In North America, dental therapy education and
      practice date back to 1972 with the establishment of training programs at the
      National School of Dental Therapy in Fort Smith, Northwest Territories, and the
      Wascana Institute of Applied Arts and Science in Regina, Saskatchewan, as a means
      of reducing access to care barriers in Canada's northern territories and to
      implement the Saskatchewan Health Dental Plan, respectively. At present, dental
      therapy in North America has reached a crossroads: in the United States, the
      profession is cautiously being explored as a solution for improving access to
      care in at-risk populations. In 2011, Canada's sole training program, the
      National School of Dental Therapy in Prince Albert, Saskatchewan, closed when the
      federal government eliminated its funding. This article examines the impact of
      private practice employment of dental therapists in Saskatchewan on the supply of
      dental therapist human resources for health in Canada's three northern
      territories (Northwest Territories, Nunavut, and Yukon), its role in the closure
      of the National School of Dental Therapy in 2011, and ramifications for the
      future of dental therapy in Canada.

PMID- 22855597
TI  - Summary: Possible futures for dental practice and dental education.

PMID- 22855600
TI  - Perioperative management of patients on chronic antithrombotic therapy.
AB  - Perioperative management of antithrombotic therapy is a situation that occurs
      frequently and requires consideration of the patient, the procedure, and an
      expanding array of anticoagulant and antiplatelet agents. Preoperative assessment
      must address each patient's risk for thromboembolic events balanced against the
      risk for perioperative bleeding. Procedures can be separated into those with a
      low bleeding risk, which generally do not require complete reversal of the
      antithrombotic therapy, and those associated with an intermediate or high
      bleeding risk. For patients who are receiving warfarin who need interruption of
      the anticoagulant, consideration must be given to whether simply withholding the
      anticoagulant is the optimal approach or whether a perioperative "bridge" with an
      alternative agent, typically a low-molecular-weight heparin, should be used. The
      new oral anticoagulants dabigatran and rivaroxaban have shorter effective half
      lives, but they introduce other concerns for perioperative management, including
      prolonged drug effect in patients with renal insufficiency, limited experience
      with clinical laboratory testing to confirm lack of residual anticoagulant
      effect, and lack of a reversal agent. Antiplatelet agents must also be considered
      in the perioperative setting, with particular consideration given to the
      potential risk for thrombotic complications in patients with coronary artery
      stents who have antiplatelet therapy withheld.

PMID- 22855598
TI  - Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other
      p53-related genes in peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies of mature T
      lymphocytes with 5-year overall survival rates of only ~ 35%. Improvement in
      outcomes has been stymied by poor understanding of the genetics and molecular
      pathogenesis of PTCL, with a resulting paucity of molecular targets for therapy.
      We developed bioinformatic tools to identify chromosomal rearrangements using
      genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and
      applied these tools to 16 PTCL patient tissue samples and 6 PTCL cell lines.
      Thirteen recurrent abnormalities were identified, of which 5 involved p53-related
      genes (TP53, TP63, CDKN2A, WWOX, and ANKRD11). Among these abnormalities were
      novel TP63 rearrangements encoding fusion proteins homologous to DeltaNp63, a
      dominant-negative p63 isoform that inhibits the p53 pathway. TP63 rearrangements
      were seen in 11 (5.8%) of 190 PTCLs and were associated with inferior overall
      survival; they also were detected in 2 (1.2%) of 164 diffuse large B-cell
      lymphomas. As TP53 mutations are rare in PTCL compared with other malignancies,
      our findings suggest that a constellation of alternate genetic abnormalities may
      contribute to disruption of p53-associated tumor suppressor function in PTCL.

PMID- 22855599
TI  - CD25 expression status improves prognostic risk classification in AML independent
      of established biomarkers: ECOG phase 3 trial, E1900.
AB  - We determined the prognostic relevance of CD25 (IL-2 receptor-alpha) expression
      in 657 patients (<= 60 years) with de novo acute myeloid leukemia (AML) treated
      in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25(POS)
      myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics.
      CD25 expression correlated with expression of stem cell antigen CD123. In
      multivariate analysis, controlled for prognostic baseline characteristics and
      daunorubicin dose, CD25(POS) patients had inferior complete remission rates (P =
      .0005) and overall survival (P < .0001) compared with CD25(NEG) cases. In a
      subset of 396 patients, we integrated CD25 expression with somatic mutation
      status to determine whether CD25 impacted outcome independent of prognostic
      mutations. CD25 was positively correlated with internal tandem duplications in
      FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of
      FLT3-ITD(POS) AML was restricted to CD25(POS) patients. CD25 expression improved
      AML prognostication independent of integrated, cytogenetic and mutational data,
      such that it reallocated 11% of patients with intermediate-risk disease to the
      unfavorable-risk group. Gene expression analysis revealed that CD25(POS) status
      correlated with the expression of previously reported leukemia stem cell
      signatures. We conclude that CD25(POS) status provides prognostic relevance in
      AML independent of known biomarkers and is correlated with stem cell gene
      expression signatures associated with adverse outcome in AML.

PMID- 22855601
TI  - Induction of IL-4Ralpha-dependent microRNAs identifies PI3K/Akt signaling as
      essential for IL-4-driven murine macrophage proliferation in vivo.
AB  - Macrophage (MPhi) activation must be tightly controlled to preclude overzealous
      responses that cause self-damage. MicroRNAs promote classical MPhi activation by
      blocking antiinflammatory signals and transcription factors but also can prevent
      excessive TLR signaling. In contrast, the microRNA profile associated with
      alternatively activated MPhi and their role in regulating wound healing or
      antihelminthic responses has not been described. By using an in vivo model of
      alternative activation in which adult Brugia malayi nematodes are implanted
      surgically in the peritoneal cavity of mice, we identified differential
      expression of miR-125b-5p, miR-146a-5p, miR-199b-5p, and miR-378-3p in helminth
      induced MPhi. In vitro experiments demonstrated that miR-378-3p was specifically
      induced by IL-4 and revealed the IL-4-receptor/PI3K/Akt-signaling pathway as a
      target. Chemical inhibition of this pathway showed that intact Akt signaling is
      an important enhancement factor for alternative activation in vitro and in vivo
      and is essential for IL-4-driven MPhi proliferation in vivo. Thus, identification
      of miR-378-3p as an IL-4Ralpha-induced microRNA led to the discovery that Akt
      regulates the newly discovered mechanism of IL-4-driven macrophage proliferation.
      Together, the data suggest that negative regulation of Akt signaling via
      microRNAs might play a central role in limiting MPhi expansion and alternative
      activation during type 2 inflammatory settings.

PMID- 22855603
TI  - Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents
      and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in
      baboons.
AB  - The pathophysiology of thrombotic thrombocytopenic purpura (TTP) can be explained
      by the absence of active ADAMTS13, leading to ultra-large von Willebrand factor
      (UL-VWF) multimers spontaneously interacting with platelets. Preventing the
      formation of UL-VWF-platelet aggregates therefore is an attractive new treatment
      strategy. Here, we demonstrate that simultaneous administration of the inhibitory
      anti-VWF monoclonal antibody GBR600 and the inhibitory anti-ADAMTS13 antibody 3H9
      to baboons (prevention group) precluded TTP onset as severe thrombocytopenia and
      hemolytic anemia were absent in these animals. In addition, partial VWF
      inhibition was not enough to prevent thrombocytopenia, demonstrating the
      specificity of this therapeutic strategy. GBR600 treatment of baboons during
      acute TTP (treatment group) resulted in a rapid recovery of severe
      thrombocytopenia similar to the platelet count increases observed in TTP patients
      treated by plasma exchange. Baboons in the control group only injected with 3H9
      developed early stages of TTP as previously described. Hence, inhibiting VWF-GPIb
      interactions is an effective way to prevent and treat the early symptoms of
      acquired TTP in baboons.

PMID- 22855602
TI  - Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and
      primitive progenitor cells.
AB  - Skewing toward myeloid cell production is often observed in chronic inflammation
      and autoimmune diseases. Herein, we determined whether persistent myeloid
      activation and proinflammatory output occurring in pathologic conditions is at
      the level of hematopoietic stem and primitive progenitor cells (HSPPCs). By using
      a mouse arthritis model, we found that even though HSPPCs in arthritis still
      retained the capacity to differentiate into different lineages, they acquired
      enhanced in vitro and in vivo propensity in a disease-dependent manner to
      generate myeloid cells, the key perpetrators of tissue damage in arthritis. This
      myeloid skewing was cell intrinsic, as arthritic HSPPCs up-regulate myeloid
      specific transcripts including S100a8. Exogenous S100a8 promoted myeloid cell
      output from wild-type HSPPCs, suggesting mechanistic involvement of this gene in
      the myeloid priming that occurs in arthritic HSPPCs. Therefore, our results
      indicate that in arthritic mice, HSPPCs adopt a pathologic state that favors
      disease persistence.

PMID- 22855604
TI  - Outcome of high-risk acute myeloid leukemia after allogeneic hematopoietic cell
      transplantation: negative impact of abnl(17p) and -5/5q-.
AB  - The European LeukemiaNet classification combines a heterogeneous group of
      aberrations as adverse-risk abnormalities. Our goal was to investigate the
      outcomes associated with distinct high-risk chromosomal abnormalities in acute
      myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation
      (HSCT). We performed a retrospective cohort analysis in patients with high-risk
      AML who received first, HLA-compatible, allogeneic HSCT between January 2005 and
      December 2008. Data from 236 patients with a median age of 55 years were
      included. Because complex karyotype (CK), -5/5q-, and abnl(17p) are overlapping
      categories, a hierarchical classification system based on the presence or absence
      of abnl(17p) and -5/5q- was developed. Patients with abnl(17p) had a 2-year event
      free survival (EFS) of 11% (95% confidence interval [CI], 0%-25%), patients with 
      5/5q- but no abnl(17p) a 2-year EFS of 29% (95% CI, 14%-44%), and patients with
      adverse-risk AML but neither of the 2 marker lesions a 2-year EFS of 49% (95% CI,
      39%-59%). Notably, complex and monosomal karyotypes lost their prognostic value
      when these marker lesions were excluded. In conclusion, hierarchical
      classification of adverse-risk karyotypes by 2 marker lesions, abnl(17p) and 
      5/5q-, is effective in prognostication of the outcome of allogeneic HSCT in AML.

PMID- 22855606
TI  - Differential requirement for ROCK in dendritic cell migration within lymphatic
      capillaries in steady-state and inflammation.
AB  - Dendritic cell (DC) migration via lymphatic vessels to draining lymph nodes
      (dLNs) is crucial for the initiation of adaptive immunity. We imaged this process
      by intravital microscopy (IVM) in the ear skin of transgenic mice bearing red
      fluorescent vasculature and yellow-fluorescent DCs. DCs within lymphatic
      capillaries were rarely transported by flow, but actively migrated within
      lymphatics and were significantly faster than in the interstitium. Pharmacologic
      blockade of the Rho-associated protein kinase (ROCK), which mediates nuclear
      contraction and de-adhesion from integrin ligands, significantly reduced DC
      migration from skin to dLNs in steady-state. IVM revealed that ROCK blockade
      strongly reduced the velocity of interstitial DC migration, but only marginally
      affected intralymphatic DC migration. By contrast, during tissue inflammation,
      ROCK blockade profoundly decreased both interstitial and intralymphatic DC
      migration. Inhibition of intralymphatic migration was paralleled by a strong up
      regulation of ICAM-1 in lymphatic endothelium, suggesting that during
      inflammation ROCK mediates de-adhesion of DC-expressed integrins from lymphatic
      expressed ICAM-1. Flow chamber assays confirmed an involvement of lymphatic
      expressed ICAM-1 and DC-expressed ROCK in DC crawling on lymphatic endothelium.
      Overall, our findings further define the role of ROCK in DC migration to dLNs and
      reveal a differential requirement for ROCK in intralymphatic DC crawling during
      steady-state and inflammation.

PMID- 22855605
TI  - The murine allantois: a model system for the study of blood vessel formation.
AB  - The allantois is the embryonic precursor of the umbilical cord in mammals and is
      one of several embryonic regions, including the yolk sac and dorsal aorta, that
      undergoes vasculogenesis, the de novo formation of blood vessels. Despite its
      importance in establishing the chorioallantoic placenta and umbilical
      circulation, the allantois frequently is overlooked in embryologic studies.
      Nonetheless, recent studies demonstrate that vasculogenesis, vascular remodeling,
      and angiogenesis are essential allantois functions in the establishment of the
      chorioallantoic placenta. Here, we review blood vessel formation in the murine
      allantois, highlighting the expression of genes and involvement of pathways
      common to vasculogenesis or angiogenesis in other parts of the embryo. We discuss
      experimental techniques available for manipulation of the allantois that are
      unavailable for yolk sac or dorsal aorta, and review how this system has been
      used as a model system to discover new genes and mechanisms involved in vessel
      formation. Finally, we discuss the potential of the allantois as a model system
      to provide insights into disease and therapeutics.

PMID- 22855607
TI  - A major determinant of the immunogenicity of factor VIII in a murine model is
      independent of its procoagulant function.
AB  - A main complication of treatment of patients with hemophilia A is the development
      of anti-factor VIII (fVIII) antibodies. The immunogenicity of fVIII potentially
      is a function of its procoagulant activity, which may result in danger signals
      that drive the immune response. Alternatively, intrinsic structural elements in
      fVIII may be particularly immunogenic. Finally, VWF, the carrier protein for
      fVIII in plasma, may play a role in immune recognition. We compared the
      immunogenicity of wild-type (wt) B domain-deleted fVIII and 2 inactive fVIII
      molecules, R372A/R1689A fVIII and V634M fVIII in fVIII(-/-) and fVIII(-/-)/VWF(-/
      ) mice. R372A/R1689A fVIII lacks proteolytic recognition sites and is not
      released from VWF. In contrast, V634M fVIII undergoes proteolytic cleavage and
      dissociation from VWF. No significant difference was observed in the
      immunogenicity of wt fVIII and V634M fVIII. R372A/R1689A fVIII was slightly less
      immunogenic in a subset of immunization regimens tested. High doses of wt fVIII
      were required to produce an immune response in fVIII(-/-)/VWF(-/-) mice. Our
      results indicate that a main component of the immune response to fVIII is
      independent of its procoagulant function, is both positively and negatively
      affected by its association with VWF, and may involve intrinsic elements of fVIII
      structure.

PMID- 22855608
TI  - Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in
      children and adults with high proliferation index and no BCL2 rearrangement.
AB  - Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL)
      presenting as localized lymphadenopathy in children. Unlike conventional adult
      FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL
      are lacking, and it is uncertain whether this indolent lymphoma is defined by age
      or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found
      that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had
      > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and
      did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement
      and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a
      separate cohort of 58 adult FL (>= 18 years of age), all 13 BCL2-N/HPI cases were
      stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with
      BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult
      and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results
      confirm the highly indolent behavior of PFL and suggest that these are
      characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also
      occur in adults and are associated with indolent behavior in this patient
      population.

PMID- 22855609
TI  - Induction of functional platelets from mouse and human fibroblasts by p45NF
      E2/Maf.
AB  - Determinant factors leading from stem cells to megakaryocytes (MKs) and
      subsequently platelets have yet to be identified. We now report that a
      combination of nuclear factor erythroid-derived 2 p45 unit (p45NF-E2), Maf G, and
      Maf K can convert mouse fibroblast 3T3 cells and adult human dermal fibroblasts
      into MKs. To screen MK-inducing factors, gene expressions were compared between
      3T3 cells that do not differentiate into MKs and 3T3-L1 cells known to
      differentiate into MKs. 3T3 cells transfected with candidate factors were
      cultured in a defined MK lineage induction medium. Among the tested factors,
      transfection with p45NF-E2/MafG/MafK lead to the highest frequency of CD41
      positive cells. Adult human dermal fibroblasts transfected with these genes were
      cultured in MK lineage induction medium. Cultured cells had megakaryocytic
      features, including surface markers, ploidy, and morphology. More than 90% of MK
      sized cells expressed CD41, designated induced MK (iMK). Infusion of these iMK
      cells into immunodeficient mice led to a time-dependent appearance of CD41
      positive, platelet-sized particles. Blood samples from iMK-infused into
      thrombocytopenic immunodeficient mice were perfused on a collagen-coated chip,
      and human CD41-positive platelets were incorporated into thrombi on the chip,
      demonstrating their functionality. These findings demonstrate that a combination
      of p45NF-E2, Maf G, and Maf K is a key determinant of both megakaryopoiesis and
      thrombopoiesis.

PMID- 22855610
TI  - Inhibition of apoptosis by BCL2 prevents leukemic transformation of a murine
      myelodysplastic syndrome.
AB  - Programmed cell death or apoptosis is a prominent feature of low-risk
      myelodysplastic syndromes (MDS), although the underlying mechanism remains
      controversial. High-risk MDS have less apoptosis associated with increased
      expression of the prosurvival BCL2-related proteins. To address the mechanism and
      pathogenic role of apoptosis and BCL2 expression in MDS, we used a mouse model
      resembling human MDS, in which the fusion protein NUP98-HOXD13 (NHD13) of the
      chromosomal translocation t(2;11)(q31;p15) is expressed in hematopoietic cells.
      Hematopoietic stem and progenitor cells from 3-month-old mice had increased rates
      of apoptosis associated with increased cell cycling and DNA damage. Gene
      expression profiling of these MDS progenitors revealed a specific reduction in
      Bcl2. Restoration of Bcl2 expression by a BCL2 transgene blocked apoptosis of the
      MDS progenitors, which corrected the macrocytic anemia. Blocking apoptosis also
      restored cell-cycle quiescence and reduced DNA damage in the MDS progenitors. We
      expected that preventing apoptosis would accelerate malignant transformation to
      acute myeloid leukemia (AML). However, contrary to expectations, preventing
      apoptosis of premalignant cells abrogated transformation to AML. In contrast to
      the current dogma that overcoming apoptosis is an important step toward cancer,
      this work demonstrates that gaining a survival advantage of premalignant cells
      may delay or prevent leukemic progression.

PMID- 22855612
TI  - Ontogeny of aerodynamics in mallards: comparative performance and developmental
      implications.
AB  - Wing morphology correlates with flight performance and ecology among adult birds,
      yet the impact of wing development on aerodynamic capacity is not well
      understood. Recent work using chukar partridge (Alectoris chukar), a precocial
      flier, indicates that peak coefficients of lift and drag (C(L) and C(D)) and lift
      to-drag ratio (C(L):C(D)) increase throughout ontogeny and that these patterns
      correspond with changes in feather microstructure. To begin to place these
      results in a comparative context that includes variation in life-history
      strategy, we used a propeller and force-plate model to study aerodynamic force
      production across a developmental series of the altricial-flying mallard (Anas
      platyrhynchos). We observed the same trend in mallards as reported for chukar in
      that coefficients of vertical (C(V)) and horizontal force (C(H)) and C(V):C(H)
      ratio increased with age, and that measures of gross-wing morphology (aspect
      ratio, camber and porosity) in mallards did not account for intraspecific trends
      in force production. Rather, feather microstructure (feather unfurling, rachis
      width, feather asymmetry and barbule overlap) all were positively correlated with
      peak C(V):C(H). Throughout ontogeny, mallard primary feathers became stiffer and
      less transmissive to air at both macroscale (between individual feathers) and
      microscale (between barbs/barbules/barbicels) levels. Differences between species
      were manifest primarily as heterochrony of aerodynamic force development. Chukar
      wings generated measurable aerodynamic forces early (<8 days), and improved
      gradually throughout a 100 day ontogenetic period. Mallard wings exhibited
      delayed aerodynamic force production until just prior to fledging (day 60), and
      showed dramatic improvement within a condensed 2-week period. These differences
      in timing may be related to mechanisms of escape used by juveniles, with mallards
      swimming to safety and chukar flap-running up slopes to take refuge. Future
      comparative work should test whether the need for early onset of aerodynamic
      force production in the chukar, compared with delayed, but rapid, change in the
      mallard wing, leads to a limited repertoire of flight behavior in adult chukar
      compared with mallards.

PMID- 22855611
TI  - Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the
      FANCD2 protein.
AB  - The Fanconi anemia (FA)-BRCA pathway is critical for the repair of DNA
      interstrand crosslinks (ICLs) and the maintenance of chromosome stability. A key
      step in FA-BRCA pathway activation is the covalent attachment of monoubiquitin to
      FANCD2 and FANCI. Monoubiquitinated FANCD2 and FANCI localize in chromatin
      associated nuclear foci where they interact with several well-characterized DNA
      repair proteins. Importantly, very little is known about the structure, function,
      and regulation of FANCD2. Herein, we describe the identification and
      characterization of a CUE (coupling of ubiquitin conjugation to endoplasmic
      reticulum degradation) ubiquitin-binding domain (UBD) in FANCD2, and demonstrate
      that the CUE domain mediates noncovalent binding to ubiquitin in vitro. We show
      that although mutation of the CUE domain destabilizes FANCD2, the protein remains
      competent for DNA damage-inducible monoubiquitination and phosphorylation.
      Importantly, we demonstrate that the CUE domain is required for interaction with
      FANCI, retention of monoubiquitinated FANCD2, and FANCI in chromatin, and for
      efficient ICL repair. Our results suggest a model by which heterodimerization of
      monoubiquitinated FANCD2 and FANCI in chromatin is mediated in part through a
      noncovalent interaction between the FANCD2 CUE domain and monoubiquitin
      covalently attached to FANCI, and that this interaction shields monoubiquitinated
      FANCD2 from polyubiquitination and proteasomal degradation.

PMID- 22855613
TI  - Precocial hindlimbs and altricial forelimbs: partitioning ontogenetic strategies
      in mallards (Anas platyrhynchos).
AB  - Precocial development, in which juveniles are relatively mature at hatching or
      birth, is more common among vertebrates than altricial development, and is likely
      to be the basal condition. Altricial development characterizes many birds and
      mammals and is generally viewed as an alternate strategy, promoting fast growth
      rates, short developmental periods and relatively poor locomotor performance
      prior to attaining adult size. Many aquatic birds such as Anseriformes (ducks,
      geese and swans), Charadriformes (gulls and terns) and Gruiformes (rails) undergo
      distinctive developmental trajectories, in that hatchlings are able to run and
      swim the day they hatch, yet they do not begin to fly until fully grown. We
      hypothesized that there should be tradeoffs in apportioning bone and muscle mass
      to the hindlimb and forelimb that could account for these patterns in locomotor
      behavior within the mallard (Anas platyrhynchos). Growth of the musculoskeletal
      system in the forelimbs and hindlimbs was measured and compared with maximal
      aquatic and terrestrial sprint speeds and aerial descent rates throughout the 2
      month-long mallard ontogenetic period. At 30 days post hatching, when body mass
      is 50% of adult values, hindlimb muscle mass averages 90% and forelimb muscle
      mass averages 10% of adult values; similarly, bone growth (length and width) in
      the hindlimbs and forelimbs averages 90 and 60% of adult values, respectively.
      The attainment of mallard locomotor performance parallels the morphological
      maturation of forelimb and hindlimb morphometrics - hindlimb performance
      initiates just after hatching at a relatively high level (~50% adult values) and
      gradually improves throughout the first month of development, while forelimb
      performance is relatively non-existent at hatching (~10% adult values),
      experiencing delayed and dramatic improvement in function, and maturing at the
      time of fledging. This divergence in ontogenetic strategy between locomotor
      modules could allow developing Anseriformes to inhabit aquatic, predator-reduced
      refuges without relying on flight for juvenile escape. Furthermore, by freeing
      the forelimbs from locomotor demand early in ontogeny, Anseriformes may bypass
      the potential canalization (i.e. retention) of juvenile form present within their
      precocial hindlimbs, to dramatically depart in forelimb form and function in the
      adult.

PMID- 22855614
TI  - Autonomous measurement of ingestion and digestion processes in free-swimming
      sharks.
AB  - Direct measurement of predator feeding events would represent a major advance in
      marine trophic ecology. To date, devices available for empirically quantifying
      feeding in free-swimming fishes have relied on measuring stomach temperature, pH
      or physical motility, each of which has major practical limitations. We
      hypothesized that the considerable physical changes that occur in the stomachs of
      carnivorous predators during the processes of ingestion and digestion should be
      quantifiable using bulk electrical impedance measured across paired electrodes.
      We used a prototype archival data logging tag to record changes in impedance
      inside the stomachs of captive free-swimming tiger and sandbar sharks over
      multiple, successive feeding events. Feeding and digestion events produced
      characteristic changes in electrical impedance of the stomach contents,
      identifiable as five successive phases: (1) pre-ingestion (empty stomach), (2)
      ingestion, (3) chemical 'lag', (4) mechanical 'chyme' and (5) stomach emptying.
      The duration of the chyme phase was positively related to meal size.

PMID- 22855615
TI  - New insights from serranid fishes on the role of trade-offs in suction-feeding
      diversification.
AB  - Suction feeding is central to prey capture in the vast majority of ray-finned
      fishes and has been well studied from a detailed, mechanistic perspective.
      Several major trade-offs are thought to have shaped the diversification of
      suction-feeding morphology and behavior, and have become well established in the
      literature. We revisited several of these expectations in a study of prey capture
      morphology and kinematics in 30 species of serranid fishes, a large, ecologically
      variable group that exhibits diverse combinations of suction and forward
      locomotion. We find that: (1) diversity among species in the morphological
      potential to generate suction changes drastically across the range of attack
      speeds that species use, with all species that use high-speed attacks having low
      capacity to generate suction, whereas slow-speed attackers exhibit the full range
      of suction abilities (this pattern indicates a more complex 'ram-suction
      continuum' than previously recognized); (2) there is no trade-off between the
      mechanical advantage of the lower jaw opening lever and the speed of jaw
      depression, revealing that this simple interpretation of lever mechanics fails to
      predict kinematic diversity; (3) high-speed attackers show increased cranial
      excursions, potentially to compensate for a decrease in accuracy; (4) the amount
      of jaw protrusion is positively related to attack speed, but not suction
      capacity; and (5) a principal component analysis revealed three significant
      multivariate axes of kinematic variation among species. Two of the three axes
      were correlated with the morphological potential to generate suction, indicating
      important but complex relationships between kinematics and suction potential.
      These results are consistent with other recent studies that show that trade-offs
      derived from simple biomechanical models may be less of a constraint on the
      evolutionary diversification of fish feeding systems than previously thought.

PMID- 22855616
TI  - The sender-receiver matching hypothesis: support from the peripheral coding of
      acoustic features in songbirds.
AB  - The sender-receiver matching hypothesis predicts that species-specific features
      of vocalizations will be reflected in species-specific auditory processing. This
      hypothesis has most often been invoked to explain correlations between vocal
      frequency ranges and the frequency range of auditory sensitivity; however, it
      could apply to other structural features, such as the rise time of stimuli. We
      explored this hypothesis in five songbird species that vary in the rise times and
      frequency range of their vocalizations. We recorded auditory evoked potentials
      (AEPs) to onset and sustained portions of stimuli that varied in both frequency
      and rise time. AEPs are gross potentials generated in the auditory nerve and
      brainstem and measured from the scalp. We found that species with shorter rise
      times in their vocalizations had greater amplitude and shorter latency onset AEPs
      than species with longer rise times. We also found that species with lower
      frequency and/or more tonal vocalizations had stronger sustained AEPs that follow
      the sound pressure changes in the stimulus (i.e. frequency following responses)
      than species with higher frequency and/or less tonal vocalizations. This is the
      first study in songbirds to show that acoustic features such as rise time and
      tonality are reflected in peripheral auditory processing.

PMID- 22855617
TI  - The regulatory role of the NO/cGMP signal transduction cascade during larval
      attachment and metamorphosis of the barnacle Balanus (=Amphibalanus) amphitrite.
AB  - The barnacle Balanus amphitrite is among the most dominant fouling species on
      intertidal rocky shores in tropical and subtropical areas and is thus a target
      organism in antifouling research. After being released from adults, the swimming
      nauplius undertakes six molting cycles and then transforms into a cyprid. Using
      paired antennules, a competent cyprid actively explores and selects a suitable
      substratum for attachment and metamorphosis (collectively known as settlement).
      This selection process involves the reception of exogenous signals and subsequent
      endogenous signal transduction. To investigate the involvement of nitric oxide
      (NO) and cyclic GMP (cGMP) during larval settlement of B. amphitrite, we examined
      the effects of an NO donor and an NO scavenger, two nitric oxide synthase (NOS)
      inhibitors and a soluble guanylyl cyclase (sGC) inhibitor on settling cyprids. We
      found that the NO donor sodium nitroprusside (SNP) inhibited larval settlement in
      a dose-dependent manner. In contrast, both the NO scavenger carboxy-PTIO and the
      NOS inhibitors aminoguanidine hemisulfate (AGH) and S-methylisothiourea sulfate
      (SMIS) significantly accelerated larval settlement. Suppression of the downstream
      guanylyl cyclase (GC) activity using a GC-selective inhibitor ODQ could also
      significantly accelerate larval settlement. Interestingly, the settlement
      inhibition effects of SNP could be attenuated by ODQ at all concentrations
      tested. In the developmental expression profiling of NOS and sGC, the lowest
      expression of both genes was detected in the cyprid stage, a crucial stage for
      the larval decision to attach and metamorphose. In summary, we concluded that NO
      regulates larval settlement via mediating downstream cGMP signaling.

PMID- 22855618
TI  - Prolactin regulates luminal bicarbonate secretion in the intestine of the sea
      bream (Sparus aurata L.).
AB  - The pituitary hormone prolactin is a pleiotropic endocrine factor that plays a
      major role in the regulation of ion balance in fish, with demonstrated actions
      mainly in the gills and kidney. The role of prolactin in intestinal ion transport
      remains little studied. In marine fish, which have high drinking rates,
      epithelial bicarbonate secretion in the intestine produces luminal carbonate
      aggregates believed to play a key role in water and ion homeostasis. The present
      study was designed to establish the putative role of prolactin in the regulation
      of intestinal bicarbonate secretion in a marine fish. Basolateral addition of
      prolactin to the anterior intestine of sea bream mounted in Ussing chambers
      caused a rapid (<20 min) decrease of bicarbonate secretion measured by pH-stat. A
      clear inhibitory dose-response curve was obtained, with a maximal inhibition of
      60-65% of basal bicarbonate secretion. The threshold concentration of prolactin
      for a significant effect on bicarbonate secretion was 10 ng ml(-1), which is
      comparable with putative plasma levels in seawater fish. The effect of prolactin
      on apical bicarbonate secretion was independent of the generation route for
      bicarbonate, as shown in a preparation devoid of basolateral HCO(3)(-)/CO(2)
      buffer. Specific inhibitors of JAK2 (AG-490, 50 MUmol l(-1)), PI3K (LY-294002, 75
      MUmol l(-1)) or MEK (U-012610, 10 MUmol l(-1)) caused a 50-70% reduction in the
      effect of prolactin on bicarbonate secretion, and demonstrated the involvement of
      prolactin receptors. In addition to rapid effects, prolactin has actions at the
      genomic level. Incubation of intestinal explants of anterior intestine of the sea
      bream in vitro for 3 h demonstrated a specific effect of prolactin on the
      expression of the Slc4a4A Na(+)-HCO(3)(-) co-transporter, but not on the Slc26a6A
      or Slc26a3B Cl(-)/HCO(3)(-) exchanger. We propose a new role for prolactin in the
      regulation of bicarbonate secretion, an essential function for ion/water
      homeostasis in the intestine of marine fish.

PMID- 22855619
TI  - Magnetic compass orientation in two strictly subterranean rodents: learned or
      species-specific innate directional preference?
AB  - Evidence for magnetoreception in mammals remains limited. Magnetic compass
      orientation or magnetic alignment has been conclusively demonstrated in only a
      handful of mammalian species. The functional properties and underlying mechanisms
      have been most thoroughly characterized in Ansell's mole-rat, Fukomys anselli,
      which is the species of choice due to its spontaneous drive to construct nests in
      the southeastern sector of a circular arena using the magnetic field azimuth as
      the primary orientation cue. Because of the remarkable consistency between
      experiments, it is generally believed that this directional preference is innate.
      To test the hypothesis that spontaneous southeastern directional preference is a
      shared, ancestral feature of all African mole-rats (Bathyergidae, Rodentia), we
      employed the same arena assay to study magnetic orientation in two other mole-rat
      species, the social giant mole-rat, Fukomys mechowii, and the solitary silvery
      mole-rat, Heliophobius argenteocinereus. Both species exhibited spontaneous
      western directional preference and deflected their directional preference
      according to shifts in the direction of magnetic north, clearly indicating that
      they were deriving directional information from the magnetic field. Because all
      of the experiments were performed in total darkness, our results strongly suggest
      that all African mole-rats use a light-independent magnetic compass for near
      space orientation. However, the spontaneous directional preference is not common
      and may be either innate (but species-specific) or learned. We propose an
      experiment that should be performed to distinguish between these two
      alternatives.

PMID- 22855620
TI  - Serotonergic neuroepithelial cells of the skin in developing zebrafish:
      morphology, innervation and oxygen-sensitive properties.
AB  - In teleost fish, O(2) chemoreceptors of the gills (neuroepithelial cells or NECs)
      initiate cardiorespiratory reflexes during hypoxia. In developing zebrafish,
      hyperventilatory and behavioural responses to hypoxia are observed before
      development of gill NECs, indicating that extrabranchial chemoreceptors mediate
      these responses in embryos. We have characterised a population of cells of the
      skin in developing zebrafish that resemble O(2)-chemoreceptive gill NECs. Skin
      NECs were identified by serotonin immunolabelling and were distributed over the
      entire skin surface. These cells contained synaptic vesicles and were associated
      with nerve fibres. Skin NECs were first evident in embryos 24-26 h post
      fertilisation (h.p.f.), and embryos developed a behavioural response to hypoxia
      between 24 and 48 h.p.f. The total number of NECs declined with age from
      approximately 300 cells per larva at 3 days post-fertilisation (d.p.f.) to ~120
      cells at 7 d.p.f., and were rarely observed in adults. Acclimation to hypoxia (30
      mmHg) or hyperoxia (300 mmHg) resulted in delayed or accelerated development,
      respectively, of peak resting ventilatory frequency and produced changes in the
      ventilatory response to hypoxia. In hypoxia-acclimated larvae, the temporal
      pattern of skin NECs was altered such that the number of cells did not decrease
      with age. By contrast, hyperoxia produced a more rapid decline in NEC number. The
      neurotoxin 6-hydroxydopamine degraded catecholaminergic nerve terminals that made
      contact with skin NECs and eliminated the hyperventilatory response to hypoxia.
      These results indicate that skin NECs are sensitive to changes in O(2) and
      suggest that they may play a role in initiating responses to hypoxia in
      developing zebrafish.

PMID- 22855621
TI  - Self-perceived psychosomatic health in Swedish children, adolescents and young
      adults: an internet-based survey over time.
AB  - OBJECTIVES: The authors investigated self-perceived psychosomatic health in young
      people (10-24 years of age) in Sweden and analysed different samples during the
      years 2005 and 2007-2010 via a community website. DESIGN: Repeated cross
      sectional surveys: (1) single question on a single day in 2005. (2) One specific
      question delivered on each of eight separate days in 2005. (3) The same eight
      questions delivered to smaller groups on the same day in 2007 and then again to
      randomly selected subjects in 2010. SETTING: Validated questionnaires launched on
      the internet by a recognised Swedish community site. Study participants were
      invited to answer questions about their health with full anonymity as they logged
      into their personal area. PARTICIPANTS: 10-24-year-old children, adolescents and
      young adults. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-reported psychosomatic
      health in terms of sex and age over time. RESULTS: A large number of responses
      were obtained (up to 140 000). The response rate for the single item on stress
      was 41%. A high percentage of young subjects responded that they felt stressed
      very often/often; the numbers were higher for women (47%) than for men (29%).
      Older teenaged women had more psychosomatic complaints than did men of similar
      ages; in contrast, among 10-12-year-old children, the percentage of psychosomatic
      complaints was similar for men and women. When comparing results obtained in 2010
      with those obtained in 2007, young people of both sexes had a slightly better
      self-perceived health status in 2007. CONCLUSIONS: During the period 2005-2010 a
      high percentage of young people, particularly females, 16-18 years of age, had
      psychosomatic complaints and considered themselves as being often or very often
      stressed. These complaints were more pronounced in the older age groups. When
      directing questions to a large community, internet-based surveys appear to be
      valuable tools.

PMID- 22855622
TI  - Age differences in the associations between sick leave and aspects of health,
      psychosocial workload and family life: a cross-sectional study.
AB  - OBJECTIVES: To investigate differences in associations between sick leave and
      aspects of health, psychosocial workload, family life and work-family
      interference between four age groups (<36, 36-45, 46-55 and 55+ years). DESIGN: A
      cross-sectional study; a questionnaire was sent to the home addresses of all
      employees of a university. SETTING: A Dutch university. PARTICIPANTS: 1843
      employees returned the questionnaire (net response: 49.1%). The age distribution
      was as follows: <36: 32%; 36-45: 26%; 46-55: 27% and 55+: 12%. PRIMARY OUTCOMES:
      Frequent sick leave (FSL, >=3 times in the past 12 months) and prolonged sick
      leave (PSL, >2 weeks in total in the past 12 months). Differences between the age
      groups in independent variables and outcomes were investigated. Logistic
      regression analysis was used to calculate associations between various variables
      and the sick leave outcomes. Interaction terms were included to detect
      differences between the age groups. RESULTS: Age differences were found for many
      work- and family-related characteristics but not in the mean scores for health
      related aspects. Presence of chronic disease was reported more frequently with
      increasing age. The 55+ age group had almost two times less chance of FSL, but
      1.6 times more chance of PSL than the <36 age group. Age moderates the
      associations between career opportunities, partner's contribution in domestic
      tasks and sex, and FSL. Job security and pay, support from supervisor,
      challenging work and being breadwinner have different associations with PSL.
      However, life events in private lives and perceived health complaints are
      important in all age groups. FSL and PSL have some determinants in common, but
      there are differences between the outcomes as well. CONCLUSIONS: Age should be
      treated as a variable of interest instead of a control variable. Employers and
      occupational physicians need to be aware that each phase in life has specific
      difficulties that can lead to FSL and PSL.

PMID- 22855623
TI  - A chemical analysis examining the pharmacology of novel psychoactive substances
      freely available over the internet and their impact on public (ill)health. Legal
      highs or illegal highs?
AB  - OBJECTIVES: Public Health England aims to improve the nation's health and
      acknowledges that unhealthy lifestyles, which include drug use, undermine
      society's health and well-being. Recreational drug use has changed to include a
      range of substances sold as 'research chemicals' but known by users as 'legal
      highs' (legal alternatives to the most popular illicit recreational drugs), which
      are of an unknown toxicity to humans and often include prohibited substances
      controlled under the Misuse of Drugs Act (1971). Consequently, the long-term
      effects on users' health and inconsistent, often illegal ingredients, mean that
      this group of drugs presents a serious risk to public health both now and in the
      future. Therefore, the aim of this study was to ascertain what is in legal highs,
      their legality and safety, while considering the potential impact, these
      synthetic substances might be having on public health. DESIGN: A total of 22
      products were purchased from five different internet sites, 18 months after the
      UK ban on substituted cathinones, like mephedrone, was introduced in April 2010.
      Each substance was screened to determine its active ingredients using accepted
      analytical techniques. SETTING: The research was conducted in Leicestershire but
      has implications for the provision of primary and secondary healthcare throughout
      the UK. RESULTS: Two products, both sold as NRG-2 from different internet
      suppliers, were found to contain the banned substituted cathinones 4
      methylethcathinone (4-MEC) and 4-methylmethcathinone (4-MMC), the latter being
      present in much smaller quantities. Although sold as research chemicals and
      labelled 'not for human consumption', they are thinly disguised 'legal highs',
      available online in quantities that vary from 1 g to 1 kg. CONCLUSIONS: Despite
      amendments to legislation, prohibited class B substances are still readily
      available in large quantities over the internet. The findings suggest that these
      prohibited substances are being manufactured or imported into the UK on a large
      scale, which has serious implications for public health and clinicians who are
      ill equipped to deal with this newly emerging problem.

PMID- 22855624
TI  - Psychosocial risk factors, job characteristics and self-reported health in the
      Paris Military Hospital Group (PMHG): a cross-sectional study.
AB  - OBJECTIVES: To investigate the associations between psychosocial risk factors and
      self-reported health, taking into account other occupational risk factors.
      DESIGN: Cross-sectional survey using a self-administered questionnaire. SETTING:
      The three military hospitals in Paris, France. PARTICIPANTS: Surveys were
      distributed to 3173 employees (1807 military and 1336 civilian), a total of 1728
      employees completed surveys. Missing data prohibited the use of 26 surveys.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The authors used Karasek's model in order
      to identify psychosocial factors (psychological demands, decisional latitude,
      social support) in the workplace. The health indicator studied was self-reported
      health. Adjustments were made for covariates: age, gender, civil or military
      status, work injury, ergonomic score, physical and chemical exposures, and
      occupational profile. Occupational profile was defined by professional category,
      department, work schedule, supervisor status and service-related length in the
      hospital. RESULTS: Job strain (defined as high psychological demands and low
      decisional latitude) (adjusted OR 2.1, 95% CI 1.5 to 2.8, p<0.001) and iso-strain
      (job strain with low social support) were significantly associated with moderate
      or poor self-reported health. Among covariates, occupational profile (p<0.001)
      and an unsatisfactory ergonomic score (adjusted OR 2.3 95% CI 1.6 to 3.2,
      p<0.001) were also significantly associated with moderate or poor self-reported
      health. CONCLUSIONS: The results support findings linking moderate or poor self
      reported health to psychosocial risk factors. The results of this study suggest
      that workplace interventions that aim to reduce exposure to psychological demands
      as well as to increase decisional latitude and social support could help improve
      self-reported health.

PMID- 22855625
TI  - Mapping the receptivity of malaria risk to plan the future of control in Somalia.
AB  - OBJECTIVES: To measure the receptive risks of malaria in Somalia and compare
      decisions on intervention scale-up based on this map and the more widely used
      contemporary risk maps. DESIGN: Cross-sectional community Plasmodium falciparum
      parasite rate (PfPR) data for the period 2007-2010 corrected to a standard age
      range of 2 to <10 years (PfPR(2-10)) and used within a Bayesian space-time
      geostatistical framework to predict the contemporary (2010) mean PfPR(2-10) and
      the maximum annual mean PfPR(2-10) (receptive) from the highest predicted PfPR(2
      10) value over the study period as an estimate of receptivity. SETTING: Randomly
      sampled communities in Somalia. PARTICIPANTS: Randomly sampled individuals of all
      ages. MAIN OUTCOME MEASURE: Cartographic descriptions of malaria receptivity and
      contemporary risks in Somalia at the district level. RESULTS: The contemporary
      annual PfPR(2-10) map estimated that all districts (n=74) and population (n=8.4
      million) in Somalia were under hypoendemic transmission (<=10% PfPR(2-10)). Of
      these, 23% of the districts, home to 13% of the population, were under
      transmission of <1% PfPR(2-10). About 58% of the districts and 55% of the
      population were in the risk class of 1% to <5% PfPR(2-10). In contrast, the
      receptivity map estimated 65% of the districts and 69% of the population were
      under mesoendemic transmission (>10%-50% PfPR(2-10)) and the rest as hypoendemic.
      CONCLUSION: Compared with maps of receptive risks, contemporary maps of
      transmission mask disparities of malaria risk necessary to prioritise and sustain
      future control. As malaria risk declines across Africa, efforts must be invested
      in measuring receptivity for efficient control planning.

PMID- 22855626
TI  - Improper cause-of-death statements by specialty of certifying physician: a cross
      sectional study in two medical centres in Taiwan.
AB  - OBJECTIVE: To determine the frequency of various types of improper cause-of-death
      (COD) statements reported on death certificates and whether the frequency
      differed by specialty of the certifying physician. DESIGN: Cross-sectional
      descriptive study. SETTING: 2 medical centres in Tainan, Taiwan. PARTICIPANTS: A
      total of 2520 death certificates issued by 230 physicians. MAIN OUTCOME MEASURES:
      4 types of improper COD statements based on the criteria of correctness of the
      COD causal sequence and the level of specificity of underlying COD selected.
      RESULTS: Of 2520 death certificates analysed, 502 (19.9%) had at least one type
      of improper COD statement. However, only 235 (9.3%) sustained major errors, that
      is, 91 (3.6%) reported incorrect causal sequence and 144 (5.7%) reported only
      mechanism(s) of death (such as respiratory failure, heart failure, sepsis and
      acidosis). The improper reporting rate was highest among nephrologists (53%,
      24/45), followed by infectious diseases physicians (45%, 29/65) and was lowest
      among oncologists (6%, 57/995). CONCLUSIONS: About one-fifth issued death
      certificates sustained improper COD statements and only one-tenth had noteworthy
      errors that would threaten the quality of COD statistics. The frequency varied by
      specialty of the certifying physician because physicians in different specialties
      manage different types of diseases and conditions with contrasting complexities
      in terms of determining the causal sequence and specificity of COD statements.

PMID- 22855627
TI  - Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and
      c.101T>C (p.M34T), in a UK population study.
AB  - OBJECTIVES: To determine the carrier rate of the GJB2 mutation c.35delG and
      c.101T>C in a UK population study; to determine whether carriers of the mutation
      had worse hearing or otoacoustic emissions compared to non-carriers. DESIGN:
      Prospective cohort study. SETTING: University of Bristol, UK. PARTICIPANTS:
      Children in the Avon Longitudinal Study of Parents and Children. 9202 were
      successfully genotyped for the c.35delG mutation and c.101>T and classified as
      either carriers or non-carriers. OUTCOME MEASURES: Hearing thresholds at age 7, 9
      and 11 years and otoacoustic emissions at age 9 and 11. RESULTS: The carrier
      frequency of the c.35delG mutation was 1.36% (95% CI 1.13 to 1.62) and c.101T>C
      was 2.69% (95% CI 2.37 to 3.05). Carriers of c.35delG and c.101T>C had worse
      hearing than non-carriers at the extra-high frequency of 16 kHz. The mean
      difference in hearing at age 7 for the c.35delG mutation was 8.53 dB (95% CI
      2.99, 14.07) and 12.57 dB at age 9 (95% CI 8.10, 17.04). The mean difference for
      c.101T>C at age 7 was 3.25 dB (95% CI -0.25 to 6.75) and 7.61 dB (95% CI 4.26 to
      10.96) at age 9. Otoacoustic emissions were smaller in the c.35delG mutation
      carrier group: at 4 kHz the mean difference was -4.95 dB (95% CI -6.70 to -3.21)
      at age 9 and -3.94 dB (95% CI -5.78 to -2.10) at age 11. There was weak evidence
      for differences in otoacoustic emissions amplitude for c.101T>C carriers.
      CONCLUSION: Carriers of the c.35delG mutation and c.101T>C have worse extra-high
      frequency hearing than non-carriers. This may be a predictor for changes in lower
      frequency hearing in adulthood. The milder effects observed in carriers of
      c.101T>C are in keeping with its classification as a mutation causing
      mild/moderate hearing loss in homozygosity or compound heterozygosity.

PMID- 22855628
TI  - Dental status and incident falls among older Japanese: a prospective cohort
      study.
AB  - OBJECTIVE: To examine if self-reported number of teeth, denture use and chewing
      ability are associated with incident falls. DESIGN: Longitudinal cohort study
      (the Aichi Gerontological Evaluation Study). SETTING: 5 Japanese municipalities.
      PARTICIPANTS: 1763 community-dwelling individuals aged 65 years and older without
      experience of falls within the previous year at baseline. MAIN OUTCOME MEASURES:
      Self-reported history of multiple falls during the past year at the follow-up
      survey about 3 years later. Baseline data on the number of teeth present and/or
      denture use and chewing ability were collected using self-administered
      questionnaires. Logistic regression analyses controlled for sex, age, functional
      disability during follow-up period, depression, self-rated health and educational
      attainment. RESULTS: 86 (4.9%) subjects reported falls at the follow-up survey.
      Logistic regression models fully adjusted for all covariates showed that subjects
      having 19 or fewer teeth but not using dentures had a significantly increased
      risk for incident falls (OR 2.50, 95% CI 1.21 to 5.17, p=0.013) compared with
      those having 20 or more teeth. Among subjects with 19 or fewer teeth, their risk
      of falls was not significantly elevated so long as they wore dentures (OR 1.36,
      95% CI 0.76 to 2.45, p=0.299). No significant association was observed between
      chewing ability and incident falls in the fully adjusted model. CONCLUSIONS:
      Having 19 or fewer teeth but not using dentures was associated with higher risk
      for the incident falls in older Japanese even after adjustment for multiple
      covariates. Dental care to prevent tooth loss and denture treatment for older
      people might prevent falls, although the authors cannot exclude the possibility
      that the association is due to residual confounding.

PMID- 22855629
TI  - Inter-rater and test-retest reliability of quality assessments by novice student
      raters using the Jadad and Newcastle-Ottawa Scales.
AB  - INTRODUCTION: Quality assessment of included studies is an important component of
      systematic reviews. OBJECTIVE: The authors investigated inter-rater and test
      retest reliability for quality assessments conducted by inexperienced student
      raters. DESIGN: Student raters received a training session on quality assessment
      using the Jadad Scale for randomised controlled trials and the Newcastle-Ottawa
      Scale (NOS) for observational studies. Raters were randomly assigned into five
      pairs and they each independently rated the quality of 13-20 articles. These
      articles were drawn from a pool of 78 papers examining cognitive impairment
      following electroconvulsive therapy to treat major depressive disorder. The
      articles were randomly distributed to the raters. Two months later, each rater re
      assessed the quality of half of their assigned articles. SETTING: McMaster
      Integrative Neuroscience Discovery and Study Program. PARTICIPANTS: 10 students
      taking McMaster Integrative Neuroscience Discovery and Study Program courses.
      MAIN OUTCOME MEASURES: The authors measured inter-rater reliability using kappa
      and the intraclass correlation coefficient type 2,1 or ICC(2,1). The authors
      measured test-retest reliability using ICC(2,1). RESULTS: Inter-rater reliability
      varied by scale question. For the six-item Jadad Scale, question-specific kappas
      ranged from 0.13 (95% CI -0.11 to 0.37) to 0.56 (95% CI 0.29 to 0.83). The ranges
      were -0.14 (95% CI -0.28 to 0.00) to 0.39 (95% CI -0.02 to 0.81) for the NOS
      cohort and -0.20 (95% CI -0.49 to 0.09) to 1.00 (95% CI 1.00 to 1.00) for the NOS
      case-control. For overall scores on the six-item Jadad Scale, ICC(2,1)s for inter
      rater and test-retest reliability (accounting for systematic differences between
      raters) were 0.32 (95% CI 0.08 to 0.52) and 0.55 (95% CI 0.41 to 0.67),
      respectively. Corresponding ICC(2,1)s for the NOS cohort were -0.19 (95% CI -0.67
      to 0.35) and 0.62 (95% CI 0.25 to 0.83), and for the NOS case-control, the
      ICC(2,1)s were 0.46 (95% CI -0.13 to 0.92) and 0.83 (95% CI 0.48 to 0.95).
      CONCLUSIONS: Inter-rater reliability was generally poor to fair and test-retest
      reliability was fair to excellent. A pilot rating phase following rater training
      may be one way to improve agreement.

PMID- 22855630
TI  - The coronary CT angiography vision protocol: a prospective observational imaging
      cohort study in patients undergoing non-cardiac surgery.
AB  - INTRODUCTION: At present, physicians have a limited ability to predict major
      cardiovascular complications after non-cardiac surgery and little is known about
      the anatomy of coronary arteries associated with perioperative myocardial
      infarction. We have initiated the Coronary CT Angiography (CTA) VISION Study to
      (1) establish the predictive value of coronary CTA for perioperative myocardial
      infarction and death and (2) describe the coronary anatomy of patients that have
      a perioperative myocardial infarction. METHODS AND ANALYSIS: The Coronary CTA
      VISION Study is prospective observational study. Preoperative coronary CTA will
      be performed in 1000-1500 patients with a history of vascular disease or at least
      three cardiovascular risk factors who are undergoing major elective non-cardiac
      surgery. Serial troponin will be measured 6-12 h after surgery and daily for the
      first 3 days after surgery. Major vascular outcomes at 30 days and 1 year after
      surgery will be independently adjudicated. ETHICS AND DISSEMINATION: Coronary CTA
      results in a measurable radiation exposure that is similar to a nuclear perfusion
      scan (10-12 mSV). Treating physicians will be blinded to the CTA results until 30
      days after surgery in order to provide the most unbiased assessment of its
      prognostic capabilities. The only exception will be the presence of a left main
      stenosis >50%. This approach is supported by best available current evidence
      that, excluding left main disease, prophylatic revascularisation prior to non
      cardiac surgery does not improve outcomes. An external safety and monitoring
      committee is overseeing the study and will review outcome data at regular
      intervals. Publications describing the results of the study will be submitted to
      major peer-reviewed journals and presented at international medical conferences.

PMID- 22855632
TI  - Cost-effectiveness of ultrasound vs nerve stimulation guidance for continuous
      sciatic nerve block.
AB  - BACKGROUND: This study assessed the cost-effectiveness of ultrasound (US) vs
      nerve stimulation (NS) guidance for continuous sciatic nerve block in Danish
      elective patients undergoing major foot and ankle surgery. METHODS: > A cost
      effectiveness analysis was conducted alongside a randomized controlled trial. A
      total of 100 consecutive patients were randomly assigned to either traditional
      electrical NS or US technique for catheter insertion guidance. Information on
      effects and costs were collected prospectively. An incremental cost-effectiveness
      ratio (ICER) was calculated as the extra cost per extra successful nerve block.
      The robustness of the ICER was investigated using 4000 non-parametric bias
      corrected bootstrap replicates to calculate the likelihood that US leads to
      better effect and lower costs compared with NS guidance. RESULTS: The mean ICER
      was negative, indicating that US was a dominating technology providing both
      higher quality and lower costs. The likelihood of US being more effective and
      cheaper than NS was estimated to 84.7%. CONCLUSIONS: In this trial, US was cost
      effective. Assuming that the results are fairly generalizable, US should be the
      preferred catheter insertion technique in larger anaesthesia departments.

PMID- 22855635
TI  - Obstructive hydrocephalus, fifth nerve and hypothalamus involvement: acute
      presentation of a giant prolactinoma.
AB  - INTRODUCTION: Pituitary tumors from lactotrope cells account for about 40% of all
      functioning pituitary cancers. Men tend to present with a larger, more invasive
      and rapid growth prolactinomas than women, possibly because hypogonadism features
      are less evident. CASE REPORT: A 27-year-old, previously asymptomatic Saudi man
      presented with a 3-day history of emesis with severe left-sided frontal headache,
      left face and right upper limb numbness, with signs of obstructive hydrocephalus.
      Brain Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) revealed a
      giant pituitary mass occupying several regions (sellar, infra-sellar, and supra
      sellar) measuring 6.5 * 5.7 * 5.9 cm, and invading the sphenoid sinus as well as
      the cavernous sinuses bilaterally, with intra-pituitary hemorrhage compressing
      the third ventricle causing obstructive hydrocephalus. Prolactin levels were
      >200,000 mIU/L, consistent with invasive giant prolactinoma (IGP). He was treated
      with Cabergoline which eventually normalized the prolactin level and
      significantly reduced the size of IGP. CONCLUSION: This is a rare case of
      obstructive hydrocephalus with super-imposed intra-pituitary hemorrhage secondary
      to IGP, highlighting the importance of a full hormonal assessment for proper
      diagnosis and management.

PMID- 22855633
TI  - Effect of preoperative fever-range whole-body hyperthermia on immunological
      markers in patients undergoing colorectal cancer surgery.
AB  - BACKGROUND: Previous studies have demonstrated beneficial immunological effects
      of fever-range whole-body hyperthermia (FR-WBH) as an adjunct to non-surgical
      cancer therapy. We conducted a study of preoperative FR-WBH in patients
      undergoing colorectal cancer surgery to evaluate perioperative, hyperthermia
      induced immunomodulation. METHODS: The trial was conducted as a subject-blinded,
      controlled, randomized study. Subjects in the FR-WBH group (n=9) were treated
      with FR-WBH before operation under propofol sedation; the target core temperature
      was 39 (0.5) degrees C with 1 h warming and 2 h plateau phase. Subjects in the
      control group (n=9) were treated with propofol sedation only. Blood samples were
      acquired before and after treatment, after operation, and 24, 48 h, and 5 days
      after the end of surgery. The following parameters were measured:
      lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-alpha,
      procalcitonin (PCT), interleukin (IL)-6/10, heat shock proteins (HSPs) 60, 70,
      and 90, human leucocyte antigen-DR (HLA-DR), and LPS-binding protein (LBP).
      RESULTS: HSPs were increased in the FR-WBH group after treatment [HSP60, 48 h
      postop: 143 (41)% vs 89 (42)%, P=0.04; HSP90, postop: 111 (33)% vs 64 (31)%,
      P=0.04; HSP70: P=0.40; FR-WBH vs control, P-values for area under the level/time
      curve]. TNF-alpha levels were elevated after surgery in the control group and
      remained near baseline in the FR-WBH group [24 h postop: 73 (68)% vs 151 (72)%,
      P=0.04]. PCT increased in both groups 24 h after surgery; in the control group,
      this increase was significantly higher (P=0.02). There were no significant
      differences for IL, HLA-DR, or LBP. CONCLUSIONS: The immune system to react to
      surgical stress, as measured by a panel of laboratory indicators, might be
      improved by preoperative FR-WBH.

PMID- 22855637
TI  - A new genus and species of Metopiinae (Hymenoptera, Ichneumonidae) from Mexico.
AB  - A new genus of Metopiinae, Ojuelos Khalaim, gen. n., with a single species,
      Ojuelos juachicus Khalaim & Ruiz-Cancino, sp. n., is described from Jalisco
      Province in central Mexico. Ojuelos belongs to the group of three genera (Cubus
      Townes & Townes, Colpotrochia Holmgren and Triclistus Forster) having a high
      lamella separating the antennal sockets and reaching the median ocellus (this
      lamella possesses a dorsal groove in it, just below the median ocellus), but
      differs from these genera primarily by 1) face and clypeus not convex in lateral
      view, 2) face separated from clypeus by a shallow transverse impression, 3)
      mandible with lower tooth very strongly reduced, 4) flagellomeres of antenna
      strongly transverse, and 5) dorsal carinae of propodeum reduced. A portion of the
      key to the genera of Metopiinae is provided to distinguish the new genus.

PMID- 22855638
TI  - Taxonomic studies on genus Tetramorium Mayr (Hymenoptera, Formicidae) with report
      of two new species and three new records including a tramp species from India
      with a revised key.
AB  - Two new species of Tetramorium Mayr, namely Tetramorium shivalikensesp. n. and
      Tetramorium triangulatumsp. n. are described. Tetramorium triangulatumsp. n.
      belongs to the inglebyi-species group and is described based on worker, queen and
      male caste, while Tetramorium shivalikensesp. n. belongs to the ciliatum-species
      group and is described based on worker caste only. Three species viz.,
      Tetramorium caldarium (Roger), Tetramorium tonganum Mayr and Tetramorium urbanii
      Bolton represent first records from India. The male caste is described for the
      first time in the case of Tetramorium tonganum. Among these, Tetramorium
      caldarium is a tramp species which extends its limit to India as well. A revised
      key to the Indian ants of this genus is also provided herewith.

PMID- 22855636
TI  - Pathology of gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumor (GIST) is a well recognized and relatively well
      understood soft tissue tumor. Early events in GIST development are activating
      mutations in KIT or PDGFRA, which occur in most GISTs and encode for mutated
      tyrosine receptor kinases that are therapeutic targets for tyrosine kinase
      inhibitors, including imatinib and sunitinib. A small minority of GISTs
      possessing neither KIT nor PDGFRA mutations may have germline mutations in SDH,
      suggesting a potential role of SDH in the pathogenesis. Immunohistochemical
      detection of KIT, and more recently DOG1, has proven to be reliable and useful in
      the diagnosis of GISTs. Because current and future therapies depend on
      pathologists, it is important that they recognize KIT-negative GISTs, GISTs in
      specific clinical contexts, GISTs with unusual morphology, and GISTs after
      treatment. This review focuses on recent developments in the understanding of the
      biology, immunohistochemical diagnosis, the role of molecular analysis, and risk
      assessment of GISTs.

PMID- 22855639
TI  - White-toothed shrews (Mammalia, Soricomorpha, Crocidura) of coastal islands of
      Vietnam.
AB  - New findings of the white-toothed shrews (Crocidura spp.) from offshore islands
      of Vietnam are reported. The species identifications have been confirmed by the
      analysis of complete mitochondrial cytochrome b gene (1140 bp). Crocidura
      phuquocensis is the only species found in the Phu Quoc Island. Crocidura
      fuliginosa has been recorded from two islands of the Con Dao Archipelago (Con Son
      and Bai Canh). The occurrence of Crocidura fuliginosa in Vietnam has been
      genetically confirmed for the first time. Crocidura attenuata has been collected
      from the Cat Ba Island for the first time, and this finding corresponds well with
      the proposal that the species' distribution is confined to the north and east of
      the Red River only.

PMID- 22855640
TI  - A new species of Orobdella (Hirudinida, Arhynchobdellida, Orobdellidae) from
      Taipei, Taiwan.
AB  - A new quadrannulate species of Orobdella, Orobdella ketagalansp. n., from Taipei,
      Taiwan, is described. This is the first record of Orobdella and the family
      Orobdellidae from Taiwan. This new species possesses small, paired sperm duct
      bulbs in the male reproductive system. In addition to these bulbs, the following
      combination of characters distinguishes this new species from other quadrannulate
      species: somite IV uniannulate, male gonopore at XI b6, female gonopore at XIII
      a1, 1/2 + 4 + 1/2 between gonopores, simple tubular gastroporal duct, lacking
      epididymides, and undeveloped atrial cornua. Phylogenetic analyses using nuclear
      18S rDNA and histone H3 as well as mitochondrial COI, 12S rDNA, tRNA(Val), and
      16S rDNA markers showed that Orobdella ketagalan is related to the two Ryukyu
      Archipelago species Orobdella dolichopharynx Nakano, 2011 and Orobdella shimadae
      Nakano, 2011.

PMID- 22855641
TI  - Three new species of Atopsyche Banks (Trichoptera, Hydrobiosidae) from Brazil.
AB  - Three new species of Atopsyche Banks (Hydrobiosidae) from Brazil are described
      and illustrated: Atopscyhe (Atopsaura) blahnikisp. n., Atopsyche (Atopsyche)
      paraunasp. n., and Atopsyche (Atopsaura) galharadasp. n. Additional illustrations
      of the male genitalia of Atopsyche urumarca Schmid are provided, including its
      populational variation. Also, we provide new state records for 2 species:
      Atopsyche (Atopsyche) urumarca from Sao Paulo, and Atopsyche (Atopsaura) plancki
      Marlier from Santa Catarina.

PMID- 22855642
TI  - A new combination expands the range of the African araneid spider Singafrotypa
      (Araneae, Araneidae).
AB  - Study of the syntype of Larinioides subinermis, a species known from Ethiopia
      only, revealed that it actually belongs to Singafrotypa Benoit, 1962. We
      redescribe Singafrotypa subinermis (Caporiacco, 1940), comb. n., and provide a
      key to females of four species belonging to Singafrotypa. A distribution map for
      all species is provided.

PMID- 22855643
TI  - Does high sugar consumption exacerbate cardiometabolic risk factors and increase
      the risk of type 2 diabetes and cardiovascular disease?
AB  - Consumption of sugar has been relatively high in the Nordic countries; the impact
      of sugar intake on metabolic risk factors and related diseases has been debated.
      The objectives were to assess the effect of sugar intake (sugar-sweetened
      beverages, sucrose and fructose) on association with type 2 diabetes,
      cardiovascular disease and related metabolic risk factors (impaired glucose
      tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid,
      inflammation markers), and on all-cause mortality, through a systematic review of
      prospective cohort studies and randomised controlled intervention studies
      published between January 2000 and search dates. The methods adopted were as
      follows: the first search was run in PubMed in October 2010. A second search with
      uric acid as risk marker was run in April 2011. The total search strategy was
      rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two
      authors independently selected studies for inclusion from the 2,743 abstracts
      according to predefined eligibility criteria. The outcome was that out of the 17
      studies extracted, 15 were prospective cohort studies and two were randomised
      controlled crossover trials. All of the studies included only adults. With
      respect to incident type 2 diabetes (nine studies), four of six prospective
      cohort studies found a significant positive association for sugar-sweetened
      beverage intake. In general, larger cohort studies with longer follow-up more
      often reported positive associations, and BMI seemed to mediate part of the
      increased risk. For other metabolic or cardiovascular risk factors or outcomes,
      too few studies have been published to draw conclusions. In conclusion, data from
      prospective cohort studies published in the years 2000-2011 suggest that sugar
      sweetened beverages probably increase the risk of type 2 diabetes. For related
      metabolic risk factors, cardiovascular disease or all-cause mortality and other
      types of sugars, too few studies were available to draw conclusions.

PMID- 22855644
TI  - The urgent need for universally applicable simple screening procedures and
      diagnostic criteria for gestational diabetes mellitus--lessons from projects
      funded by the World Diabetes Foundation.
AB  - BACKGROUND: To address the risks of adverse pregnancy outcomes and future type 2
      diabetes associated with gestational diabetes mellitus (GDM), its early detection
      and timely treatment is essential. In the absence of an international consensus,
      multiple different guidelines on screening and diagnosis of GDM have existed for
      a long time. This may be changing with the publication of the recommendations by
      the International Association of Diabetes and Pregnancy Study Groups. However,
      none of these guidelines take into account evidence from or ground realities of
      resource-poor settings. OBJECTIVE: This study aimed to investigate whether GDM
      projects supported by the World Diabetes Foundation in developing countries
      utilize any of the internationally recommended guidelines for screening and
      diagnosis of GDM, explore experiences on applicability and usefulness of the
      guidelines and barriers if any, in implementing the guidelines. These projects
      have reached out to thousands of pregnant women through capacity building and
      improvement of access to GDM screening and diagnosis in the developing world and
      therefore provide a rich field experience on the applicability of the guidelines
      in resource-poor settings. DESIGN: A mixed methods approach using questionnaires
      and interviews was utilised to review 11 GDM projects. Two projects were
      conducted by the same partner; interviews were conducted in person or via phone
      by the first author with nine project partners and one responded via email. The
      interviews were analysed using content analysis. RESULTS: The projects use seven
      different screening procedures and diagnostic criteria and many do not completely
      adhere to one guideline alone. Various challenges in adhering to the
      recommendations emerged in the interviews, including problems with screening
      women during the recommended time period, applicability of some of the listed
      risk factors used for (pre-)screening, difficulties with reaching women for
      testing in the fasting state, time consuming nature of the tests, intolerance to
      high glucose load due to nausea, need for repeat tests, issues with scarcity of
      test consumables and lack of equipment making some procedures impossible to
      follow. CONCLUSION: Though an international consensus on screening and diagnosis
      for GDM is welcome, it should ensure that the recommendations take into account
      feasibility and applicability in low resource settings to ensure wider usage. We
      need to move away from purely academic discussions focusing on sensitivity and
      specificity to also include what can actually be done at the basic care level.

PMID- 22855645
TI  - Trends of blood pressure levels and management in Vasterbotten County, Sweden,
      during 1990-2010.
AB  - BACKGROUND: Availability of longitudinal data on hypertension and blood pressure
      levels are important to assess changes over time at the population level.
      Moreover, detailed information in different population sub-groups is important to
      understand inequity and social determinants of blood pressure distribution in the
      population. OBJECTIVES: The objectives of this study are to: (1) describe the
      trends of population blood pressure levels in men and women between different
      educational levels and geographic areas in Sweden during 1990-2010; (2) identify
      prevalences of hypertension, awareness, treatment, and control in the population;
      and (3) assess the 10-year risk of developing hypertension among individuals with
      normal and high normal blood pressures. METHODS: This study is based on data from
      the Vasterbotten Intervention Program (VIP) in Vasterbotten County, Sweden. The
      cross-sectional analysis includes 133,082 VIP health examinations among
      individuals aged 30, 40, 50, and 60 years from 1990 to 2010. The panel analysis
      includes 34,868 individuals who were re-examined 10 years after the baseline
      examination. Individuals completed a self-administered health questionnaire that
      covers demographic and socio-economic information, self-reported health, and
      lifestyle behaviours. Blood pressure measurement was obtained prior to the
      questionnaire. In the cross-sectional analysis, trends of blood pressure by sex,
      and between educational groups and geographic areas are presented. In the panel
      analysis, the 10-year risk of developing hypertension is estimated using the
      predicted probability from logistic regression analysis for each sex, controlling
      for age and educational level. RESULTS: The prevalence of hypertension decreased
      from 1990 to 2010; from 43.8 to 36.0% (p < 0.001) among men, and 37.6 to 27.5%
      among women (p < 0.001). Individuals with basic education had a significantly
      higher prevalence of hypertension compared to those with medium or high
      education. Although the decreases were observed in all geographic areas,
      individuals in rural inland areas had a much higher prevalence compared to those
      who lived in Umea City. The proportion of hypertensive women who were aware of
      their hypertension (61.7%) was significantly higher than men (51.6%). About 34%
      of men and 42% of women with hypertension reported taking blood pressure
      medication. Over time, awareness and control of hypertension improved (from 46.5%
      in 1990 to 69% in 2010 and from 30 to 65%, respectively). The gaps between
      educational groups diminished. This study shows a significantly higher risk of
      developing hypertension for men and women with high normal blood pressure
      compared to those with normal blood pressure at baseline in all age cohorts and
      educational groups. The average risks of developing hypertension among men with
      high normal blood pressure were 21.5, 45.8, and 56.3% in the 30, 40, and 50-year
      cohorts, respectively. Corresponding numbers for women were 22.6, 47.4, and
      57.9%. CONCLUSIONS: Levels of blood pressure and hypertension decreased
      significantly among the Vasterbotten population in the last 21 years.
      Hypertension management has improved and there is increased awareness, treatment,
      and control of blood pressure. Despite these achievements, the persisting social
      gaps in blood pressure levels and management demand further investigation and
      action from policy makers. Future research should attempt to identify and address
      the root causes of these health inequities to ensure better and equal health for
      the whole population.

PMID- 22855646
TI  - Mechanisms for achieving adolescent-friendly services in Ecuador: a realist
      evaluation approach.
AB  - BACKGROUND: Despite evidence showing that adolescent-friendly health services
      (AFSs) increase young people's access to these services, health systems across
      the world are failing to integrate this approach. In Latin America, policies
      aimed at strengthening AFS abound. However, such services are offered only in a
      limited number of sites, and providers' attitudes and respect for confidentiality
      have not been addressed to a sufficient extent. METHODS: The aim of this study
      was to explore the mechanisms that triggered the transformation of an 'ordinary'
      health care facility into an AFS in Ecuador. For this purpose, a realist
      evaluation approach was used in order to analyse three well-functioning AFSs.
      Information was gathered at the national level and from each of the settings
      including: (i) statistical information and unpublished reports; (ii) in-depth
      interviews and focus group discussions with policy makers, health care providers,
      users and adolescents participating in youth organisations and (iii) observations
      at the health care facilities. Thematic analysis was carried out, driven by the
      realist evaluation approach, namely exploring the connections between mechanisms,
      contexts and outcomes. RESULTS: The results highlighted that the development of
      the AFSs was mediated by four mechanisms: grounded self-confidence in trying new
      things, legitimacy, a transformative process and an integral approach to
      adolescents. Along this process, contextual factors at the national and
      institutional levels were further explored. CONCLUSION: The Ministry of Health of
      Ecuador, based on the New Guidelines for Comprehensive Care of Adolescent Health,
      has started the scaling up of AFSs. Our research points towards the need to
      recognise and incorporate these mechanisms as part of the implementation strategy
      from the very beginning of the process. Although contextually limited to Ecuador,
      many mechanisms and good practices in these AFS may be relevant to the Latin
      American setting and elsewhere.

PMID- 22855648
TI  - Genetic Overlap between Holoprosencephaly and Kallmann Syndrome.
AB  - Patients with Kallmann syndrome (KS; congenital hypogonadotropic hypogonadism and
      decreased/absent sense of smell), septo-optic dysplasia (SOD), or
      holoprosencephaly (HPE) reportedly have midline defects. In this study, we
      investigate a genetic overlap between KS, SOD, and HPE. Nineteen subjects (18
      males, 1 female) with KS and without mutations in the known KS genes were
      screened for mutations in SOX2, SHH, SIX3,TGIF1,TDGF1,FOXH1,GLI2, and GLI3. One
      male carried 2 heterozygous missense changes, one in SIX3 (c.428G>A, p.G143D) and
      the other in GLI2 (c.2509G>A, p.E837K). Both of these genes have been implicated
      in the etiology of HPE and neither of these changes were present in 200 control
      subjects. Other variants found among the subjects were known polymorphisms. KS
      and HPE may display a genetic overlap. The involvement of genes implicated in the
      etiology of midline defects in patients with KS warrants further studies.

PMID- 22855649
TI  - Two Missense Mutations in the Primary Autosomal Recessive Microcephaly Gene MCPH1
      Disrupt the Function of the Highly Conserved N-Terminal BRCT Domain of
      Microcephalin.
AB  - Primary microcephaly MCPH1 is an extremely rare autosomal recessive disorder
      associated with congenital microcephaly, mental retardation and a distinctive
      cellular phenotype of misregulated chromosome condensation. The MCPH1 gene
      encodes an 835-amino acid protein, microcephalin, which contains 1 N-terminal and
      2 C-terminal BRCT (BRCA1 C-terminus) domains. BRCT domains are predominantly
      found in proteins involved in cell cycle control and DNA repair. Here we describe
      1 novel and 1 previously reported MCPH1 missense mutation, p.Trp75Arg and
      p.Ser72Leu, respectively, in the N-terminal BRCT domain of microcephalin
      associated with severe congenital microcephaly. Both residues are entirely
      conserved in the MCPH1 orthologs of all vertebrate species and Drosophila.
      Proliferating lymphocytes of the patients with p.Trp75Arg and p.Ser72Leu show the
      unique cellular MCPH1 phenotype of misregulated chromosome condensation,
      indicating that these missense alterations disrupt the function of the N-terminal
      BRCT domain of the protein. Interestingly, both residues are strictly conserved
      in BRCT domains of BRCA1. ClustalW alignments show that the residue p.Ser72 of
      microcephalin corresponds to p.Ser1715 of the N-terminal BRCT domain of BRCA1,
      while the microcephalin residue p.Trp75 is analogous to p.Trp1718 in the N
      terminal BRCT and to p.Trp1837 in C-terminal BRCT domains of BRCA1. Missense
      alterations for all 3 corresponding BRCA1 residues were described and are
      predicted to be deleterious resulting in the destabilization of the BRCA1
      protein. Our data on the 2 MCPH1 missense alterations provide further evidence
      for the functional significance of these residues in BRCT domains.

PMID- 22855650
TI  - Neuropsychopathology in 7 Patients with the 22q13 Deletion Syndrome: Presence of
      Bipolar Disorder and Progressive Loss of Skills.
AB  - The 22q13 deletion syndrome is characterised by intellectual disability (ID),
      delayed or absent speech, autistic-like behaviour and minor, nonspecific
      dysmorphic features. The deletion of the SHANK3 gene is thought to be responsible
      for these features. In this study, the clinical data of 7 patients with the 22q13
      deletion syndrome are presented, obtained by clinical genetic examination, direct
      behavioural observation and by interview of family members and/or caregivers,
      complemented by behavioural questionnaires. The specific focus was on behaviour,
      psychopathology and the level of functioning during life course in order to
      determine common features that might contribute to the delineation of the
      syndrome. Major findings were a high incidence of psychiatric disorders, more in
      particular bipolar disorder (BPD) and attention deficit hyperactivity disorder
      (ADHD), and a sudden deterioration after acute events, in addition to a
      progressive loss of skills over years. Therefore, a deletion of SHANK3 may result
      in a dysfunctional nervous system, more susceptible to developmental problems and
      psychiatric disorders on the one hand, less able to recuperate after psychiatric
      and somatic events, and more vulnerable to degeneration at long term on the other
      hand. These results are exploratory and need to be confirmed in a larger sample.

PMID- 22855651
TI  - Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian
      Patient with Symphalangism Syndrome.
AB  - Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by
      stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and
      conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist
      essential for normal bone and joint development in humans and mice. Autosomal
      dominant mutations have been described in the NOG gene, encoding the noggin
      protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG
      mutation (L46P) based on a c.137T>C transition. A different pathogenic mutation
      in the same codon (L46D) has been previously described in an in vivo chicken
      model. An in silico model shows a decreased binding affinity between noggin and
      BMP7 for both L46D and L46P compared to the wild type. Therefore, this codon
      should play an important role in BMP7 binding activity of the noggin protein and
      consequently to the joint morphogenesis.

PMID- 22855652
TI  - Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome.
AB  - Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the
      COH1 gene. It is characterized by intellectual disability, hypotonia, joint
      hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some
      cases, intermittent isolated neutropenia. We investigated an Italian patient with
      CS together with his family. Genetic analysis disclosed 2 novel mutations: the
      first is an intronic mutation (c.8697-9A>G) creating a new splice site 8
      nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA)
      generating a premature stop codon. The compound heterozygous mutations explain
      the proband's phenotype and improved the knowledge of genotype-phenotype
      correlation.

PMID- 22855653
TI  - NRAS Mutations in Noonan Syndrome.
AB  - Noonan syndrome is a genetically heterogeneous disorder caused by mutations in
      PTPN11, SOS1, RAF1 and less frequently in KRAS, NRAS or SHOC2. Here, we performed
      mutation analysis of NRAS and SHOC2 in 115 PTPN11, SOS1, RAF1, and KRAS mutation
      negative individuals. No SHOC2 mutations were found, but we identified 3 NRAS
      mutations in 3 probands. One NRAS mutation was novel. The phenotype associated
      with germline NRAS mutations is variable. Our results confirm that a small
      proportion of Noonan syndrome patients carry germline NRAS mutations.

PMID- 22855654
TI  - Interstitial 4q Deletion and Isodicentric Y-Chromosome in a Patient with
      Dysmorphic Features.
AB  - We present a 2-year-old boy with a de novo
      46,XY,idic(Y)(q11.221),del(4)(q26q31.1) karyotype. G-banding, FISH, MLPA, and SNP
      array techniques were used to characterize the 24-Mb deletion in 4q and the
      breakpoint in the isodicentric Y-chromosome region between 15,982,252 and
      15,989,842 bp. The patient presented with mild facial dysmorphism, hemangioma,
      mild frontal cerebral atrophy, and Dandy-Walker variant. Essentially, this case
      reveals that patients can present more complex genomic imbalances than initially
      suspected.

PMID- 22855655
TI  - A Case of KIT-Negative Extra-Gastrointestinal Stromal Tumor of the Lesser
      Omentum.
AB  - We report the unique case of a 69-year-old man with an extra-gastrointestinal
      stromal tumor (EGIST) in the lesser omentum. Based on the location of the tumor
      and the radiological findings, we made a provisional diagnosis of hepatic
      cavernous hemangioma in the lateral segment. However, after 5 years of follow-up,
      tumor growth was noted and the patient underwent a laparotomy. The tumor was
      located in the lesser omentum and resected en bloc with its fused lesser omentum
      and an adherent portion of the liver. The pathology results indicated an EGIST
      with microscopic proliferation of epithelioid cells in the lesser omentum; the
      tumor was immunohistochemically negative for KIT staining and positive for CD34
      and PKC theta. Because of the rarity of mitotic figures and the low Ki-67
      labeling, the tumor was diagnosed as a KIT-negative EGIST with a low malignant
      potential. The patient was followed up without receiving imatinib mesylate
      treatment and has remained free of any signs of recurrence for 26 months. The
      present case report describes a very rare lesser omental KIT-negative EGIST.

PMID- 22855656
TI  - Transient Psychotic Episode Induced by Helicobacter pylori Triple Therapy
      Treatment.
AB  - The term 'antibiomania' refers to manic episodes that occur after a patient
      starts taking antibiotics. We report the case of a 49-year-old male who developed
      acute psychosis secondary to initiation of triple therapy for Helicobacter pylori
      eradication. Unlike with proton pump inhibitors, there have been several reported
      cases of central nervous system side effects and psychiatric consequences due to
      amoxicillin, however evidence points to clarithromycin as the likely culprit. On
      average onset of symptoms occurred within 1-5 days of initiating therapy. In all
      cases, symptoms resolved upon cessation of clarithromycin, mostly within 1-3
      days. Unfortunately, the mechanism through which clarithromycin causes
      neurotoxicity remains unclear. Clinicians should be cognizant of psychiatric side
      effects secondary to clarithromycin, and discontinuation should be prompt for
      rapid recovery of mental status.

PMID- 22855657
TI  - A patient with chronic hepatitis C and a pancreatic mass in endoscopic
      ultrasound.
AB  - We report a rare case of pancreas tumor (lymphoma) in a patient with a history of
      chronic hepatitis C virus (HCV) infection without treatment, with a high viral
      load (20,199,805 IU/ml). He presented with abdominal pain, jaundice, weight loss
      and sweating. Computed tomography showed a hypodense mass located in the head of
      the pancreas, and immunohistochemistry of a specimen obtained by endoscopic
      ultrasound-guided fine needle aspiration revealed non-Hodgkin's lymphoma of the
      pancreas, B cell type. An association of HCV infection with pancreatic lymphoma
      has only been reported rarely in the literature and its clinical significance is
      uncertain.

PMID- 22855659
TI  - Clues for diagnosing primary pancreatic lymphoma.
AB  - Primary pancreatic lymphoma (PPL), a localized lymphoma in the pancreas, accounts
      for <0.5% of all pancreatic masses and presents with symptoms favoring the more
      common adenocarcinoma. It is important to differentiate PPL from adenocarcinoma
      since treatment and prognosis differ considerably. PPL is potentially curable
      with chemotherapy, especially if it is diagnosed at early stages. A definitive
      diagnosis can only be based on histopathological findings. Endoscopic ultrasound
      guided fine needle aspiration (EUS-guided FNA) is a reliable, minimally invasive
      and cost-effective method for this purpose. Even though there are neither typical
      clinical features nor specific biomarker for the diagnosis of PPL, certain common
      presentations have been observed which may indicate PPL. We herein present the
      case of a 43-year-old man who was successfully diagnosed with PPL by EUS-guided
      FNA. His clinical, laboratory and radiographic findings supported PPL over
      adenocarcinoma as well. This case demonstrates that high clinical suspicion based
      on clinical, laboratory and imaging features is critical in PPL diagnosis and
      management.

PMID- 22855658
TI  - Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis.
AB  - Familial hypobetalipoproteinemia (FHBL) is a rare genetic disorder of lipid
      metabolism that is associated with abnormally low serum levels of low-density
      lipoprotein (LDL) cholesterol and apolipoprotein B. It is an autosomal co
      dominant disorder, and depending on zygosity, the clinical manifestations may
      vary from none to neurological, endocrine, hematological or liver dysfunction.
      Nonalcoholic fatty liver disease is common in persons with FHBL, however
      progression to nonalcoholic steatohepatitis is unusual. We describe here a
      patient with a novel APOB mutation, V703I, which appears to contribute to the
      severity of the FHBL phenotype. He had liver enzyme abnormalities, increased
      echogenicity of the liver consistent with steatosis, very low LDL cholesterol at
      0.24 mmol/l (normal 1.8-3.5 mmol/l) and an extremely low apolipoprotein B level
      of 0.16 g/l (normal 0.6-1.2 g/l). APOB gene sequencing revealed him to be a
      compound heterozygote with two mutations (R463W and V703I). APOB R463W has
      previously been reported to cause FHBL. Genetic sequencing of his first-degree
      relatives identified the APOB V703I mutation in his normolipidemic brother and
      father and the APOB R463W mutation in his mother and sister, both of whom have
      very low LDL cholesterol levels. These results suggest that the APOB V703I
      mutation alone does not cause the FHBL phenotype. However, it is possible that it
      has a contributory role to a more aggressive phenotype in the presence of APOB
      R463W.

PMID- 22855660
TI  - Metabolic alkalosis, acute renal failure and epileptic seizures as unusual
      manifestations of an upside-down stomach.
AB  - Upside-down stomach represents a critical and rare manifestation of hiatal
      hernias. Here we report on a 60-year-old male patient who was admitted to our
      hospital with epileptic seizures and dehydration. Laboratory tests revealed
      severe metabolic alkalosis (pH 7.56) with low potassium (2.7 mmol/l),
      hypochloremia (<60 mmol/l), increased hematocrit (53%) and high levels of serum
      creatinine (651 umol/l). Based on a history of recurrent vomiting, gastroscopy
      and computed tomography were performed. Both diagnostics showed an upside-down
      stomach with signs of incarceration. Upon infusion of sodium chloride 0.9%, acid
      base state, electrolyte balance and renal function became improved. Subsequently,
      the patient was referred to the department of surgery for hiatoplasty with
      fundoplication. This case report highlights severe metabolic and neurological
      disorders as unusual and life-threatening complications of an upside-down
      stomach.

PMID- 22855661
TI  - Complicated cholelithiasis: an unusual combination of acute pancreatitis and
      bouveret syndrome.
AB  - Bouveret syndrome is a rare form of gallstone ileus. The purpose of the present
      study was to present the unusual case of a female patient with complicated
      cholelithiasis manifested as a combination of acute pancreatitis and concomitant
      Bouveret syndrome. A 61-year-old female patient was admitted to the emergency
      department complaining of mid-epigastric and right upper quadrant abdominal pain
      radiating band-like in the thoracic region of the back as well as repeated
      episodes of vomiting over the last 24 h. The initial correct diagnosis of
      pancreatitis was subsequently combined with the diagnosis of Bouveret syndrome as
      a computed tomography scan revealed the presence of a gallstone within the
      duodenum causing luminal obstruction. After failure of endoscopic gallstone
      removal, a surgical approach was undertaken where gallstone removal was followed
      by cholecystectomy and restoration of the anatomy by eliminating the fistula. The
      concomitant pancreatitis complicated the postoperative period and prolonged the
      length of hospital stay. However, the patient was discharge on the 45th
      postoperative day. Attempts for endoscopic removal of the impacted stone should
      be the initial therapeutic step. Surgery should be reserved for cases refractory
      to endoscopic intervention and when definite treatment is the actual challenge.

PMID- 22855662
TI  - Unusual Manifestation of Gastric Helicobacter pylori Infection.
AB  - Infection with Helicobacter pylori (HP) is common in many parts of the world.
      While most patients are asymptomatic, it causes peptic ulcer disease and
      malignancy in some of them. Other rare conditions have occasionally been reported
      in association with this infection. We report a case of hypertrophic gastropathy
      caused by HP in a 52-year-old asymptomatic patient. He was found to have marked
      enlargement of the gastric mucosal folds on radiological imaging and endoscopy. A
      gastric mucosal biopsy showed HP colonization associated with neutrophilic
      inflammation. After exclusion of neoplasia, other infections and infiltrative
      disorders, HP was thought to be the cause of the gastric fold hypertrophy. The
      patient responded well to HP eradication therapy, with normalization of the
      gastric mucosal folds. HP infection should be considered in the differential
      diagnosis of hypertrophic gastropathy and treated accordingly.

PMID- 22855663
TI  - Jejunal scarf-covering method in pancreaticojejunostomy after total gastrectomy.
AB  - Pancreatic fistula is the most serious postoperative complication after
      pancreaticoduodenectomy, and it leads to intra-abdominal abscess, sepsis,
      hemorrhage and high mortality. To prevent pancreatic fistula, wrapping of
      skeletonized vessels and the anastomotic site of the pancreaticoenterostomy using
      the round ligament, greater omentum, or both has been evaluated. However, the
      round ligament and greater omentum have already been resected in patients who
      have previously undergone total gastrectomy, making them unavailable in
      pancreaticoduodenectomy. Therefore, we developed a procedure for wrapping the
      anastomotic site of the pancreaticojejunostomy using the jejunum, namely the
      'jejunal scarf-covering method' as a novel technique to prevent pancreatic
      fistula following pancreaticoduodenectomy in patients who have previously
      undergone total gastrectomy.

PMID- 22855664
TI  - Chylous ascites secondary to giant liver hemangioma.
AB  - Chylous ascites is rare in clinical practice. It is characterized by milky
      appearing peritoneal fluid with a triglycerides concentration of >1.25 mmol/l
      (110 mg/dl). Its pathophysiology is related to a disruption in the normal
      lymphatic flow. It is more common after trauma (including post surgery),
      neoplasia or atypical infections such as tuberculosis or filariasis. Other rare
      medical causes have been reported. The treatment is supportive and focused on
      correction of the underlying pathology. We report here the first case of chylous
      ascites caused by giant liver hemangioma and discuss the management of this
      condition.

PMID- 22855665
TI  - Colon carcinoma with unusual metastasis to the esophagus manifesting as multiple
      nodules and Dysphagia: management with systemic chemotherapy.
AB  - We present here the rare clinical case of a 44-year-old gentleman with metastasis
      from colon carcinoma to the esophagus presenting with multiple nodules and
      dysphagia, which was successfully managed with systemic chemotherapy. The patient
      presented at our institution with 3-month history of dysphagia almost 4 years
      after being operated for stage III carcinoma in the sigmoid colon. Endoscopic
      findings showed multiple nodules at the gastroesophageal junction and mid
      esophagus. Histological features and immunostains confirmed the diagnosis of
      metastatic colon carcinoma. Because of evidence of extensive metastatic disease
      in the spine and liver requiring systemic therapy, the patient was treated with
      chemotherapy with irinotecan and cetuximab, with subsequent improvement in tumor
      markers, liver metastasis and symptoms of dysphagia. Even though repeat endoscopy
      showed no improvement in esophageal nodules, the overall response to chemotherapy
      was positive. In conclusion, we present a very rare, previously unreported case
      of metastases from colon cancer to the esophagus presenting as non-obstructive
      nodules and dysphagia that responded to systemic chemotherapy.

PMID- 22855666
TI  - Obstructing gangliocytic paraganglioma in the third portion of the duodenum.
AB  - Gangliocytic paragangliomas are infrequent tumors almost exclusively found in the
      second portion of the duodenum. An unusual case of a gangliocytic paraganglioma
      in the third portion of the duodenum with obstructive symptoms is herein
      reported. A 16-year-old male patient presented with epigastric pain, postprandial
      plenitude and reflux. A barium swallow failed to demonstrate abnormalities.
      Endoscopy showed a pedunculated submucosal tumor, originating at the third
      duodenal portion and causing partial obstruction. Biopsy was not performed due to
      the risk of bleeding. CT scan demonstrated a polypoid lesion. Through a
      transmesocolic approach and an anterior duodenotomy, resection of the tumor was
      performed. No lymph node or other organ affection was found. Histologic
      examination revealed a gangliocytic paraganglioma. Immunohistochemical
      examination was performed. Gangliocytic paragangliomas originating in the third
      or fourth portion of the duodenum, as in the present case, are extremely rare.
      Characteristic histologic features including epithelioid cells, spindle-shaped
      cells and ganglion-like cells were met. The majority of cases manifest with a
      similar benign behavior. Local resection of the tumor is recommended for these
      cases. An infrequent case of a gangliocytic paraganglioma located in the third
      portion of the duodenum, with a less common clinical presentation, is herein
      reported.

PMID- 22855667
TI  - Rare endoscopic manifestation of pancreatic adenocarcinoma.
AB  - Gastric ulcer secondary to direct invasion from pancreatic adenocarcinoma is
      rare. Metastases to the stomach have been commonly reported with melanoma and
      with primary tumors of the breast, lung, ovary, liver, colon and testis. We
      report a patient who presented with epigastric pain and in whom subsequently
      upper endoscopy showed a malignant gastric ulcer secondary to direct invasion
      from pancreatic adenocarcinoma of the body. An 81-year-old female presented to
      our hospital with epigastric pain and subsequently underwent endoscopy with
      endoscopic ultrasound for evaluation of a pancreatic body mass. She had a large
      gastric ulcer in the fundus which was in direct continuity with the pancreatic
      mass. Pathology from biopsy of the ulcer revealed invasive well-to-moderately
      differentiated adenocarcinoma, and immunohistochemical stains were strongly
      positive for CA19-9, CK7, CK19 and carcinoembryonic antigen. These findings were
      consistent with a histopathological diagnosis of metastatic carcinoma of the
      pancreas. Patients with gastrointestinal metastases usually have advanced
      malignancy with poor prognosis. Endoscopic evaluation with adequate biopsies
      should be performed for symptomatic patients.

PMID- 22855668
TI  - Idiopathic granulomatous gastritis resembling a gastrointestinal stromal tumor.
AB  - A 41-year-old female presented with a 2 cm gastric submucosal tumor that was
      suspected to be a gastrointestinal stromal tumor or other malignancy, and local
      resection of the stomach was performed. However, histopathological examination
      showed granulomatous gastritis (GG) with a variety of chronic inflammatory cells
      and multinodular granulomas. Although she had a past history of tuberculosis and
      advanced breast cancer after surgery, there was no apparent evidence of either
      tuberculosis or a metastatic tumor. Other causes of GG, such as mycosis,
      syphilis, sarcoidosis or foreign body reaction were also excluded. There were no
      clinical features of Crohn's disease as the principal differential diagnosis.
      Therefore, she was diagnosed to have idiopathic granulomatous gastritis (IGG).
      IGG is rare with few reports, and this report presents a surgical case of IGG
      resembling a gastrointestinal stromal tumor.

PMID- 22855670
TI  - Functional organization and adaptability of a decision-making network in aplysia.
AB  - Whereas major insights into the neuronal basis of adaptive behavior have been
      gained from the study of automatic behaviors, including reflexive and rhythmic
      motor acts, the neural substrates for goal-directed behaviors in which decision
      making about action selection and initiation are crucial, remain poorly
      understood. However, the mollusk Aplysia is proving to be increasingly relevant
      to redressing this issue. The functional properties of the central circuits that
      govern this animal's goal-directed feeding behavior and particularly the neural
      processes underlying the selection and initiation of specific feeding actions are
      becoming understood. In addition to relying on the intrinsic operation of central
      networks, goal-directed behaviors depend on external sensory inputs that through
      associative learning are able to shape decision-making strategies. Here, we will
      review recent findings on the functional design of the central network that
      generates Aplysia's feeding-related movements and the sensory-derived plasticity
      that through learning can modify the selection and initiation of appropriate
      action. The animal's feeding behavior and the implications of decision-making
      will be briefly described. The functional design of the underlying buccal network
      will then be used to illustrate how cellular diversity and the coordination of
      neuronal burst activity provide substrates for decision-making. The contribution
      of specific synaptic and neuronal membrane properties within the buccal circuit
      will also be discussed in terms of their role in motor pattern selection and
      initiation. The ability of learning to "rigidify" these synaptic and cellular
      properties so as to regularize network operation and lead to the expression of
      stereotyped rhythmic behavior will then be described. Finally, these aspects will
      be drawn into a conceptual framework of how Aplysia's goal-directed circuitry
      compares to the central pattern generating networks for invertebrate rhythmic
      behaviors.

PMID- 22855671
TI  - The basic circuit of the IC: tectothalamic neurons with different patterns of
      synaptic organization send different messages to the thalamus.
AB  - The inferior colliculus (IC) in the midbrain of the auditory system uses a unique
      basic circuit to organize the inputs from virtually all of the lower auditory
      brainstem and transmit this information to the medial geniculate body (MGB) in
      the thalamus. Here, we review the basic circuit of the IC, the neuronal types,
      the organization of their inputs and outputs. We specifically discuss the large
      GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the
      more numerous glutamatergic neurons. The somata and dendrites of LG neurons are
      identified by axosomatic glutamatergic synapses that are lacking in the other
      cell types and exclusively contain the glutamate transporter VGLUT2. Although LG
      neurons are most numerous in the central nucleus of the IC (ICC), an analysis of
      their distribution suggests that they are not specifically associated with one
      set of ascending inputs. The inputs to ICC may be organized into functional zones
      with different subsets of brainstem inputs, but each zone may contain the same
      three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG
      neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary
      complex, intermediate nucleus of the lateral lemniscus, and IC itself that
      express the gene for VGLUT2 only are the likely origin of the dense VGLUT2
      axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG
      neurons are GABAergic tectothalamic neurons in addition to the numerous
      glutamatergic tectothalamic neurons. SG neurons evidently target other auditory
      structures. The basic circuit of the IC and the LG neurons in particular, has
      implications for the transmission of information about sound through the midbrain
      to the MGB.

PMID- 22855669
TI  - Critical evaluation of ayurvedic plants for stimulating intrinsic antioxidant
      response.
AB  - Oxidative damage caused by free radicals plays an important role in the causation
      and progression of many diseases, including aging. Free-radical damage is
      countered by many mechanisms, including both active antioxidant enzymatic
      activity in our body and passive antioxidants. Antioxidant response of our body
      can accommodate increased oxidative damage in diseased states to a level but
      beyond that level, additional antioxidants are required to combat the increased
      stress. Apart from the regular dietary sources of antioxidants, many traditional
      herbal medicines demonstrate a potential to boost antioxidant activity. Rasayana
      chikitsa that deals with rejuvenation and revitalization is a branch of the
      Indian traditional medical system of ayurveda. We review some select herbs
      described in rasayana chikitsa that have been assessed by modern means for
      stimulating intrinsic antioxidant responses in humans. A critical evaluation of
      rasayana chikitsa will likely provide urgently needed, actual stimulants of our
      physiological antioxidant responses and not just more passive antioxidants to add
      to an already large catalog.

PMID- 22855673
TI  - The effects of cues on neurons in the basal ganglia in Parkinson's disease.
AB  - Visual cues open a unique window to the understanding of Parkinson's disease
      (PD). These cues can temporarily but dramatically improve PD motor symptoms.
      Although details are unclear, cues are believed to suppress pathological basal
      ganglia (BG) activity through activation of corticostriatal pathways. In this
      study, we investigated human BG neurophysiology under different cued conditions.
      We evaluated bursting, 10-30 Hz oscillations (OSCs), and directional tuning (DT)
      dynamics in the subthalamic nucleus (STN) activity while seven patients executed
      a two-step motor task. In the first step (predicted +cue), the patient moved to a
      target when prompted by a visual go cue that appeared 100% of the time. Here, the
      timing of the cue is predictable and the cue serves an external trigger to
      execute a motor plan. In the second step, the cue appeared randomly 50% of the
      time, and the patient had to move to the same target as in the first step. When
      it appeared (unpredicted +cue), the motor plan was to be triggered by the cue,
      but its timing was not predictable. When the cue failed to appear (unpredicted 
      cue), the motor plan was triggered by the absence of the visual cue. We found
      that during predicted +cue and unpredicted -cue trials, OSCs significantly
      decreased and DT significantly increased above baseline, though these modulations
      occurred an average of 640 ms later in unpredicted -cue trials. Movement and
      reaction times were comparable in these trials. During unpredicted +cue trials,
      OSCs, and DT failed to modulate though bursting significantly decreased after
      movement. Correspondingly, movement performance deteriorated. These findings
      suggest that during motor planning either a predictably timed external cue or an
      internally generated cue (generated by the absence of a cue) trigger the
      execution of a motor plan in premotor cortex, whose increased activation then
      suppresses pathological activity in STN through direct pathways, leading to motor
      facilitation in PD.

PMID- 22855672
TI  - Monkey in the middle: why non-human primates are needed to bridge the gap in
      resting-state investigations.
AB  - Resting-state investigations based on the evaluation of intrinsic low-frequency
      fluctuations of the BOLD fMRI signal have been extensively utilized to map the
      structure and dynamics of large-scale functional network organization in humans.
      In addition to increasing our knowledge of normal brain connectivity, disruptions
      of the spontaneous hemodynamic fluctuations have been suggested as possible
      diagnostic indicators of neurological and psychiatric disease states. Though the
      non-invasive technique has been received with much acclamation, open questions
      remain regarding the origin, organization, phylogenesis, as well as the basis of
      disease-related alterations underlying the signal patterns. Experimental work
      utilizing animal models, including the use of neurophysiological recordings and
      pharmacological manipulations, therefore, represents a critical component in the
      understanding and successful application of resting-state analysis, as it affords
      a range of experimental manipulations not possible in human subjects. In this
      article, we review recent rodent and non-human primate studies and based on the
      examination of the homologous brain architecture propose the latter to be the
      best-suited model for exploring these unresolved resting-state concerns. Ongoing
      work examining the correspondence of functional and structural connectivity,
      state-dependency and the neuronal correlates of the hemodynamic oscillations are
      discussed. We then consider the potential experiments that will allow insight
      into different brain states and disease-related network disruptions that can
      extend the clinical applications of resting-state fMRI (RS-fMRI).

PMID- 22855674
TI  - Neurocognitive correlates of the effects of yoga meditation practice on emotion
      and cognition: a pilot study.
AB  - Mindfulness meditation involves attending to emotions without cognitive fixation
      of emotional experience. Over time, this practice is held to promote alterations
      in trait affectivity and attentional control with resultant effects on well-being
      and cognition. However, relatively little is known regarding the neural
      substrates of meditation effects on emotion and cognition. The present study
      investigated the neurocognitive correlates of emotion interference on cognition
      in Yoga practitioners and a matched control group (CG) underwent fMRI while
      performing an event-related affective Stroop task. The task includes image
      viewing trials and Stroop trials bracketed by neutral or negative emotional
      distractors. During image viewing trials, Yoga practitioners exhibited less
      reactivity in right dorsolateral prefrontal cortex (dlPFC) to negative as
      compared to neutral images; whereas the CG had the opposite pattern. A main
      effect of valence (negative > neutral) was observed in limbic regions (e.g.,
      amygdala), of which the magnitude was inversely related to dlPFC activation.
      Exploratory analyses revealed that the magnitude of amygdala activation predicted
      decreased self-reported positive affect in the CG, but not among Yoga
      practitioners. During Stroop trials, Yoga practitioners had greater activation in
      ventrolateral prefrontal cortex (vlPFC) during Stroop trials when negative,
      compared to neutral, emotional distractor were presented; the CG exhibited the
      opposite pattern. Taken together, these data suggest that though Yoga
      practitioners exhibit limbic reactivity to negative emotional stimuli, such
      reactivity does not have downstream effects on later mood state. This uncoupling
      of viewing negative emotional images and affect among Yoga practitioners may be
      occasioned by their selective implementation of frontal executive-dependent
      strategies to reduce emotional interference during competing cognitive demands
      and not during emotional processing per se.

PMID- 22855675
TI  - Facial mimicry and the mirror neuron system: simultaneous acquisition of facial
      electromyography and functional magnetic resonance imaging.
AB  - Numerous studies have shown that humans automatically react with congruent facial
      reactions, i.e., facial mimicry, when seeing a vis-a-vis' facial expressions. The
      current experiment is the first investigating the neuronal structures responsible
      for differences in the occurrence of such facial mimicry reactions by
      simultaneously measuring BOLD and facial EMG in an MRI scanner. Therefore, 20
      female students viewed emotional facial expressions (happy, sad, and angry) of
      male and female avatar characters. During picture presentation, the BOLD signal
      as well as M. zygomaticus major and M. corrugator supercilii activity were
      recorded simultaneously. Results show prototypical patterns of facial mimicry
      after correction for MR-related artifacts: enhanced M. zygomaticus major activity
      in response to happy and enhanced M. corrugator supercilii activity in response
      to sad and angry expressions. Regression analyses show that these congruent
      facial reactions correlate significantly with activations in the IFG, SMA, and
      cerebellum. Stronger zygomaticus reactions to happy faces were further associated
      to increased activities in the caudate, MTG, and PCC. Corrugator reactions to
      angry expressions were further correlated with the hippocampus, insula, and STS.
      Results are discussed in relation to core and extended models of the mirror
      neuron system (MNS).

PMID- 22855676
TI  - Use of tactile feedback to control exploratory movements to characterize object
      compliance.
AB  - Humans have been shown to be good at using active touch to perceive subtle
      differences in compliance. They tend to use highly stereotypical exploratory
      strategies, such as applying normal force to a surface. We developed similar
      exploratory and perceptual algorithms for a mechatronic robotic system (Barrett
      arm/hand system) equipped with liquid-filled, biomimetic tactile sensors
      (BioTac((r)) from SynTouch LLC). The distribution of force on the fingertip was
      measured by the electrical resistance of the conductive liquid trapped between
      the elastomeric skin and a cluster of four electrodes on the flat fingertip
      surface of the rigid core of the BioTac. These signals provided closed-loop
      control of exploratory movements, while the distribution of skin deformations,
      measured by more lateral electrodes and by the hydraulic pressure, were used to
      estimate material properties of objects. With this control algorithm, the robot
      plus tactile sensor was able to discriminate the relative compliance of various
      rubber samples.

PMID- 22855677
TI  - Novel Mutations of the GNE Gene in Distal Myopathy with Rimmed Vacuoles
      Presenting with Very Slow Progression.
AB  - We report novel compound heterozygous mutations of the UDP-N-acetylglucosamine-2
      epimerase and N-acetylmannosamine kinase (GNE) gene, c.302G>A (p.R101H) and c.617
      4A>G, in a Japanese family with distal myopathy with rimmed vacuoles (DMRV)
      presenting with slow progression. The three patients could stand and walk even
      36, 34, and 39 years after onset, respectively, although affected individuals
      become wheelchair bound on average 12 years after onset of the disease. The
      clinical spectrum of DMRV seems to be wider than previously thought in terms of
      both the clinical course and the severity of the disease.

PMID- 22855678
TI  - Hypertropia following Spontaneous Resolution of Brown's Syndrome.
AB  - PURPOSE: To report a case of bilateral Brown's syndrome with unilateral
      spontaneous resolution causing hypertropia and significant head tilt. CASE
      REPORT: A 3 1/2-year-old girl presented with bilateral typical Brown's syndrome
      and orthophoria in the primary position; she presented with unilateral resolution
      of right Brown's syndrome 6 months later, causing right hypertropia and gradually
      deteriorating left head tilt. She benefited from right superior rectus muscle
      recession to help correct her head posture. CONCLUSION: This is the first report
      of a patient presenting with known bilateral Brown's syndrome with subsequent
      documented unilateral resolution causing a significant hypertropia of the
      resolved side and contralateral head tilt. Our case provides evidence in support
      of Clark and Noel's [Can J Ophthalmol 1993;28:213-216] hypothesis that patients
      who present with unilateral Brown's syndrome and contralateral inferior oblique
      muscle overaction might originally have had bilateral Brown's syndrome with
      spontaneous resolution of 1 side only.

PMID- 22855679
TI  - Generational differences in the orientation of time in cantonese speakers as a
      function of changes in the direction of chinese writing.
AB  - It has long been argued that spatial aspects of language influence people's
      conception of time. However, what spatial aspect of language is the most
      influential in this regard? To test this, two experiments were conducted in Hong
      Kong and Macau with literate Cantonese speakers. The results suggest that the
      crucial factor in literate Cantonese people's spatial conceptualization of time
      is their experience with writing and reading Chinese script. In Hong Kong and
      Macau, Chinese script is written either in the traditional vertical orientation,
      which is still used, or the newer horizontal orientation, which is more common
      these days. Before the 1950s, the dominant horizontal direction was right-to
      left. However, by the 1970s, the dominant horizontal direction had become left-to
      right. In both experiments, the older participants predominately demonstrated
      time in a right-to-left direction, whereas younger participants predominately
      demonstrated time in a left-to-right direction, consistent with the horizontal
      direction that was prevalent when they first became literate.

PMID- 22855680
TI  - Once bitten, twice shy: on the transient nature of congruency sequence effects.

PMID- 22855681
TI  - Spinal injuries in children.
AB  - About 5% of spinal injuries occur in children - however the consequences to the
      society are devastating, all the more so because the cervical spine is more
      commonly affected. Anatomical differences with adults along with the inherent
      elasticity of the pediatric spine, makes these injuries a biomechanically
      separate entity. Hence clinical manifestations are unique, one of which is the
      Spinal Cord Injury Without Radiological Abnormality. With the advent of high
      quality MRI and CT scan along with digital X-ray, it is now possible to exactly
      delineate the anatomical location, geometrical configuration, and the
      pathological extent of the injury. This has improved the management strategies of
      these unfortunate children and the role of surgical stabilization in unstable
      injuries can be more sharply defined. However these patients should be followed
      up diligently because of the recognized long term complications of spinal
      deformity and syringomyelia.

PMID- 22855682
TI  - Age-related changes in sleep and circadian rhythms: impact on cognitive
      performance and underlying neuroanatomical networks.
AB  - Circadian and homeostatic sleep-wake regulatory processes interact in a fine
      tuned manner to modulate human cognitive performance. Dampening of the circadian
      alertness signal and attenuated deterioration of psychomotor vigilance in
      response to elevated sleep pressure with aging change this interaction pattern.
      As evidenced by neuroimaging studies, both homeostatic sleep pressure and
      circadian sleep-wake promotion impact on cognition-related cortical and arousal
      promoting subcortical brain regions including the thalamus, the anterior
      hypothalamus, and the brainstem locus coeruleus (LC). However, how age-related
      changes in circadian and homeostatic processes impact on the cerebral activity
      subtending waking performance remains largely unexplored. Post-mortem studies
      point to neuronal degeneration in the SCN and age-related modifications in the
      arousal-promoting LC. Alongside, cortical frontal brain areas are particularly
      susceptible both to aging and misalignment between circadian and homeostatic
      processes. In this perspective, we summarize and discuss here the potential
      neuroanatomical networks underlying age-related changes in circadian and
      homeostatic modulation of waking performance, ranging from basic arousal to
      higher order cognitive behaviors.

PMID- 22855684
TI  - White matter abnormalities in patients with focal cortical dysplasia revealed by
      diffusion tensor imaging analysis in a voxelwise approach.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) allows the analysis of changes in
      microstructure, through the quantification of the spread and direction of water
      molecules in tissues. We used fractional anisotropy (FA) maps to compare the
      integrity of WM between patients and controls. The objective of the present study
      was to investigate WM abnormalities in patients with frontal lobe epilepsy
      secondary to focal cortical dysplasia (FCD). MATERIALS AND METHODS: We included
      31 controls (12 women, 33.1 +/- 9.6 years, mean +/- SD) and 22 patients (11
      women, 30.4 +/- 10.0 years), recruited from our outpatient clinic. They had
      clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on
      MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained
      in 32 directions and b value of 1000 s/mm(2). To process the DTI we used the
      following softwares: MRIcroN and FSL/TBSS (tract-based spatial statistics). We
      used a threshold-free cluster enhancement with significance at p < 0.05, fully
      corrected for multiple comparisons across space. RESULTS: Areas with FA reduction
      in patients were identified in both hemispheres, mainly in the frontal lobes,
      cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p
      = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and
      inferior fronto-occipital fasciculus (p = 0.042). CONCLUSION: Our results showed
      a widespread pattern of WM microstructural abnormalities extending beyond the
      main lesion seen on MRI (frontal lobe), which may be related to frequent seizures
      or to the extent of MRI-invisible portion of FCD.

PMID- 22855683
TI  - Inhibition of A5 Neurons Facilitates the Occurrence of REM Sleep-Like Episodes in
      Urethane-Anesthetized Rats: A New Role for Noradrenergic A5 Neurons?
AB  - When rapid eye movement (REM) sleep occurs, noradrenergic cells become silent,
      with the abolition of activity in locus coeruleus (LC) neurons seen as a key
      event permissive for the occurrence of REM sleep. However, it is not known
      whether silencing of other than LC noradrenergic neurons contributes to the
      generation of REM sleep. In urethane-anesthetized rats, stereotyped REM sleep
      like episodes can be repeatedly elicited by injections of the cholinergic
      agonist, carbachol, into a discrete region of the dorsomedial pons. We used this
      preparation to test whether inhibition of ventrolateral pontine noradrenergic A5
      neurons only, or together with LC neurons, also can elicit REM sleep-like
      effects. To silence noradrenergic cells, we sequentially injected the alpha(2)
      adrenergic agonist clonidine (20-40 nl, 0.75 mM) into both A5 regions and then
      the LC. In two rats, successful bilateral clonidine injections into the A5 region
      elicited the characteristic REM sleep-like episodes (hippocampal theta rhythm,
      suppression of hypoglossal nerve activity, reduced respiratory rate). In five
      rats, bilateral clonidine injections into the A5 region and then into one LC
      triggered REM sleep-like episodes, and in two rats injections into both A5 and
      then both LC were needed to elicit the effect. In contrast, in three rats, uni-
      or bilateral clonidine injections only into the LC had no effect, and clonidine
      injections placed in another six rats outside of the A5 and/or LC regions were
      without effect. The REM sleep-like episodes elicited by clonidine had similar
      magnitude of suppression of hypoglossal nerve activity (by 75%), similar pattern
      of hippocampal changes, and similar durations (2.5-5.3 min) to the episodes
      triggered in the same preparation by carbachol injections into the dorsomedial
      pontine reticular formation. Thus, silencing of A5 cells may importantly enable
      the occurrence of REM sleep-like episodes, at least under anesthesia. This is a
      new role for noradrenergic A5 neurons.

PMID- 22855685
TI  - Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy
      Receptors, and Viral Receptors.
AB  - Chemokine receptors (CKRs) function in the inflammatory response and in
      vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologs
      with modified functions from those of the typical CKRs. The decoy receptors are
      able to bind ligands without signaling. On the other hand, the viral receptors
      show constitutive signaling without ligands. We examined the sites related to the
      functional difference. At first, the decoy and viral receptors were each
      classified into five groups, based on the molecular phylogenetic analysis. A
      multiple amino acid sequence alignment between each group and the CKRs was then
      constructed. The difference in the amino acid composition between the group and
      the CKRs was evaluated as the Kullback-Leibler (KL) information value at each
      alignment site. The KL information value is considered to reflect the difference
      in the functional constraints at the site. The sites with the top 5% of KL
      information values were selected and mapped on the structure of a CKR. The
      comparisons with decoy receptor groups revealed that the detected sites were
      biased on the intracellular side. In contrast, the sites detected from the
      comparisons with viral receptor groups were found on both the extracellular and
      intracellular sides. More sites were found in the ligand binding pocket in the
      analyses of the viral receptor groups, as compared to the decoy receptor groups.
      Some of the detected sites were located in the GPCR motifs. For example, the DRY
      motif of the decoy receptors was often degraded, although the motif of the viral
      receptors was basically conserved. The observations for the viral receptor groups
      suggested that the constraints in the pocket region are loose and that the sites
      on the intracellular side are different from those for the decoy receptors, which
      may be related to the constitutive signaling activity of the viral receptors.

PMID- 22855686
TI  - Species tropism of HIV-1 modulated by viral accessory proteins.
AB  - Human immunodeficiency virus type 1 (HIV-1) is tropic and pathogenic only for
      humans, and does not replicate in macaque monkeys routinely used for experimental
      infections. This specially narrow host range (species tropism) has impeded much
      the progress of HIV-1/acquired immunodeficiency syndrome (AIDS) basic research.
      Extensive studies on the underlying mechanism have revealed that Vif, one of
      viral accessory proteins, is critical for the HIV-1 species tropism in addition
      to Gag-capsid protein. Another auxiliary protein Vpu also has been demonstrated
      to affect this HIV-1 property. In this review, we focus on functional
      interactions of these HIV-1 proteins and species specific-restriction factors. In
      addition, we describe an evolutional viewpoint that is relevant to the species
      tropism of HIV-1 controlled by the accessory proteins.

PMID- 22855688
TI  - A Survey of MicroRNA Length Variants Contributing to miRNome Complexity in Peach
      (Prunus Persica L.).
AB  - MicroRNAs (miRNAs) are short non-coding RNA molecules produced from hairpin
      structures and involved in gene expression regulation with major roles in plant
      development and stress response. Although each annotated miRNA in miRBase
      (www.mirbase.org) is a single defined sequence with no further details on
      possible variable sequence length, isomiRs - namely the population of variants of
      miRNAs coming from the same precursors - have been identified in several species
      and could represent a way of broadening the regulatory network of the cell. Next
      gen-based sequencing makes it possible to comprehensively and accurately assess
      the entire miRNA repertoire including isomiRs. The aim of this work was to survey
      the complexity of the peach miRNome by carrying out Illumina high-throughput
      sequencing of miRNAs in three replicates of five biological samples arising from
      a set of different peach organs and/or phenological stages. Three hundred-ninety
      two isomiRs (miRNA and miRNA*-related) corresponding to 26 putative miRNA coding
      loci, have been highlighted by mirDeep-P and analyzed. The presence of the same
      isomiRs in different biological replicates of a sample and in different tissues
      demonstrates that the generation of most of the detected isomiRs is not random.
      The degree of mature sequence heterogeneity is very different for each individual
      locus. Results obtained in the present work can thus contribute to a deeper view
      of the miRNome complexity and to better explore the mechanism of action of these
      tiny regulators.

PMID- 22855687
TI  - Therapeutical measures to control airway tolerance in asthma and lung cancer.
AB  - Airway tolerance is a specialized immunological surveillance which is activated
      by the cells of the lung to deal with and distinguish between innocuous and
      pathogenic inhalants. However, this distinction does not always occur. Airway
      tolerance is necessary to avoid the development of allergic disorders, such as
      asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in
      the airways. By contrast, tumor cells induce tolerogenic factors in their
      microenvironment to evade T-cell mediated anti-tumor-immune responses. This
      review updates current understandings on the effect of the cytokines TGF-beta, IL
      10, and IL-17A on the lung immune responses to antigen, and analyzes their
      involvement in allergic asthma and lung cancer. The aim of the review is to
      evaluate where therapeutic intervention may be feasible and where it might fail.
      The multifunctional role of these cytokines further complicates the decision on
      the timing and concentration for their use as therapeutical targets. In fact, TGF
      beta has suppressive activity in early tumorigenesis, but may become tumor
      promoting in the later stages of the disease. This dual behavior is sometimes due
      to changes in the cellular target of TGF-beta, and to the expansion of the
      induced (i)-Tregs. Similarly, IL-17A has been found to elicit pro- as well as
      anti-tumor properties. Thus, this pro-inflammatory cytokine induces the
      production of IL-6 which interferes with Treg development. Yet IL-17A could
      promote tumor growth in conjunction with IL-6-dependent activation of Stat3.
      Thus, understanding the mechanisms of airway tolerance could help to improve the
      therapy to both, allergic asthma and lung cancer. Hereby, asthma therapy aims to
      induce and maintain tolerance to inhaled allergens and therapy against lung
      cancer tries to inhibit the tolerogenic response surrounding the tumor.

PMID- 22855689
TI  - Comparative study of visual inspection of the cervix using acetic acid (VIA) and
      Papanicolaou (Pap) smears for cervical cancer screening.
AB  - This article is a comparative study of two screening methods for pre-invasive
      lesions of the cervix. The Papanicolaou (Pap) smear, an old and tested screening
      method, is compared with the findings from visual inspection of the cervix
      following acetic acid (VIA) wash. VIA is a new screening method being advocated
      by the World Health Organization as an alternative to Pap smear in low-resource
      settings. OBJECTIVE: The objective of this article is to compare the sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of VIA and Pap smear. METHODS: This was a comparative study carried out in the
      postnatal clinic of Ahmadu Bello University Teaching Hospital, Zaria. Pap smear
      samples were taken by the researcher. Samples were fixed in 95% ethyl alcohol and
      taken to the Pathology Department for interpretation. The cervix was then painted
      with 3-5% VIA and observed for aceto-white lesions. Suspected areas were biopsied
      and transported to the Pathology Department for interpretation. Patients with
      positive Pap smear results were also called back for biopsy. Biopsy served as the
      reference standard. RESULTS: There were 351 samples that were suitable for
      statistical analysis. The sensitivity of VIA was 60%, specificity 94.4%, positive
      predictive value 50%, negative predictive value 99.4%, and accuracy was 98.6%.
      Pap smear had a sensitivity of 60%, specificity of 100%, positive predictive
      value of 100%, negative predictive value of 99.4%, and accuracy of 99.4%.
      CONCLUSIONS: VIA had a comparable result with Pap smear. It should be
      incorporated into our national screening programme to complementthe cervical
      cytology in low-resource settings similar to ours.

PMID- 22855690
TI  - Evidence that marine reserves enhance resilience to climatic impacts.
AB  - Establishment of marine protected areas, including fully protected marine
      reserves, is one of the few management tools available for local communities to
      combat the deleterious effect of large scale environmental impacts, including
      global climate change, on ocean ecosystems. Despite the common hope that reserves
      play this role, empirical evidence of the effectiveness of local protection
      against global problems is lacking. Here we show that marine reserves increase
      the resilience of marine populations to a mass mortality event possibly caused by
      climate-driven hypoxia. Despite high and widespread adult mortality of benthic
      invertebrates in Baja California, Mexico, that affected populations both within
      and outside marine reserves, juvenile replenishment of the species that supports
      local economies, the pink abalone Haliotis corrugata, remained stable within
      reserves because of large body size and high egg production of the protected
      adults. Thus, local protection provided resilience through greater resistance and
      faster recovery of protected populations. Moreover, this benefit extended to
      adjacent unprotected areas through larval spillover across the edges of the
      reserves. While climate change mitigation is being debated, coastal communities
      have few tools to slow down negative impacts of global environmental shifts.
      These results show that marine protected areas can provide such protection.

PMID- 22855691
TI  - Intranasal vaccination with murabutide enhances humoral and mucosal immune
      responses to a virus-like particle vaccine.
AB  - Murabutide (MB) is a synthetic immunomodulator recognized by the nucleotide
      binding oligomerization domain-containing protein 2 (NOD2) receptor on mammalian
      cells. MB has previously been approved for testing in multiple human clinical
      trials to determine its value as an antiviral therapeutic, and as an adjuvant for
      injected vaccines. We have found a new use for this immunomodulator; it functions
      as a mucosal adjuvant that enhances immunogenicity of virus-like particles (VLP)
      administered intranasally. MB enhanced Norwalk virus (NV) VLP-specific IgG
      systemically and IgA production at distal mucosal sites following intranasal (IN)
      vaccination. A dose escalation study identified 100 ug as the optimal MB dosage
      in mice, based on the magnitude of VLP-specific IgG, IgG1, IgG2a and IgA
      production in serum and VLP-specific IgA production at distal mucosal sites. IN
      vaccination using VLP with MB was compared to IN delivery VLP with cholera toxin
      (CT) or gardiquimod (GARD) and to parenteral VLP delivery with alum; the MB
      groups were equivalent to CT and GARD and superior to alum in inducing mucosal
      immune responses and stimulated equivalent systemic VLP-specific antibodies.
      These data support the further testing of MB as a potent mucosal adjuvant for
      inducing robust and durable antibody responses to non-replicating subunit
      vaccines.

PMID- 22855692
TI  - Novel Cell and Tissue Acquisition System (CTAS): microdissection of live and
      frozen brain tissues.
AB  - We developed a novel, highly accurate, capillary based vacuum-assisted
      microdissection device CTAS-Cell and Tissue Acquisition System, for efficient
      isolation of enriched cell populations from live and freshly frozen tissues,
      which can be successfully used in a variety of molecular studies, including
      genomics and proteomics. Specific diameter of the disposable capillary unit (DCU)
      and precisely regulated short vacuum impulse ensure collection of the desired
      tissue regions and even individual cells. We demonstrated that CTAS is capable of
      dissecting specific regions of live and frozen mouse and rat brain tissues at the
      cellular resolution with high accuracy. CTAS based microdissection avoids
      potentially harmful physical treatment of tissues such as chemical treatment,
      laser irradiation, excessive heat or mechanical cell damage, thus preserving
      primary functions and activities of the dissected cells and tissues. High quality
      DNA, RNA, and protein can be isolated from CTAS-dissected samples, which are
      suitable for sequencing, microarray, 2D gel-based proteomic analyses, and Western
      blotting. We also demonstrated that CTAS can be used to isolate cells from native
      living tissues for subsequent recultivation of primary cultures without affecting
      cellular viability, making it a simple and cost-effective alternative for laser
      assisted microdissection.

PMID- 22855693
TI  - Evolution of the vertebrate paralemmin gene family: ancient origin of gene
      duplicates suggests distinct functions.
AB  - Paralemmin-1 is a protein implicated in plasma membrane dynamics, the development
      of filopodia, neurites and dendritic spines, as well as the invasiveness and
      metastatic potential of cancer cells. However, little is known about its mode of
      action, or about the biological functions of the other paralemmin isoforms:
      paralemmin-2, paralemmin-3 and palmdelphin. We describe here evolutionary
      analyses of the paralemmin gene family in a broad range of vertebrate species.
      Our results suggest that the four paralemmin isoform genes (PALM1, PALM2, PALM3
      and PALMD) arose by quadruplication of an ancestral gene in the two early
      vertebrate genome duplications. Paralemmin-1 and palmdelphin were further
      duplicated in the teleost fish specific genome duplication. We identified a
      unique sequence motif common to all paralemmins, consisting of 11 highly
      conserved residues of which four are invariant. A single full-length paralemmin
      homolog with this motif was identified in the genome of the sea lamprey
      Petromyzon marinus and an isolated putative paralemmin motif could be detected in
      the genome of the lancelet Branchiostoma floridae. This allows us to conclude
      that the paralemmin gene family arose early and has been maintained throughout
      vertebrate evolution, suggesting functional diversification and specific
      biological roles of the paralemmin isoforms. The paralemmin genes have also
      maintained specific features of gene organisation and sequence. This includes the
      occurrence of closely linked downstream genes, initially identified as a
      readthrough fusion protein with mammalian paralemmin-2 (Palm2-AKAP2). We have
      found evidence for such an arrangement for paralemmin-1 and -2 in several
      vertebrate genomes, as well as for palmdelphin and paralemmin-3 in teleost fish
      genomes, and suggest the name paralemmin downstream genes (PDG) for this new gene
      family. Thus, our findings point to ancient roles for paralemmins and distinct
      biological functions of the gene duplicates.

PMID- 22855694
TI  - Pathology Imaging Informatics for Clinical Practice and Investigative and
      Translational Research.
AB  - Pathologists routinely interpret gross and microscopic specimens to render
      diagnoses and to engage in a broad spectrum of investigative research. Multiple
      studies have demonstrated that imaging technologies have progressed to a level at
      which properly digitized specimens provide sufficient quality comparable to the
      traditional glass slides examinations. Continued advancements in this area will
      have a profound impact on the manner in which pathology is conducted from this
      point on. Several leading institutions have already undertaken ambitious projects
      directed toward digitally imaging, archiving, and sharing pathology specimens. As
      a result of these advances, the use of informatics in diagnostic and
      investigative pathology applications is expanding rapidly. In addition, the
      advent of novel technologies such as multispectral imaging makes it possible to
      visualize and analyze imaged specimens using multiple wavelengths simultaneously.
      As these powerful technologies become increasingly accepted and adopted, the
      opportunities for gaining new insight into the underlying mechanisms of diseases
      as well as the potential for discriminating among subtypes of pathologies are
      growing accordingly.

PMID- 22855695
TI  - A half century (1961-2011) of applying microsurgery to experimental liver
      research.
AB  - The development of microsurgery has been dependent on experimental animals.
      Microsurgery could be a very valuable technique to improve experimental models of
      liver diseases. Microdissection and microsutures are the two main microsurgical
      techniques that can be considered for classifying the experimental models
      developed for liver research in the rat. Partial portal vein ligation,
      extrahepatic cholestasis and hepatectomies are all models based on
      microdissection. On the other hand, in portacaval shunts, orthotopic liver
      transplantation and partial heterotopic liver transplantation, the microsuture
      techniques stand out. By reducing surgical complications, these microsurgical
      techniques allow for improving the resulting experimental models. If good
      experimental models for liver research are successfully developed, the results
      obtained from their study might be particularly useful in patients with liver
      disease. Therefore experimental liver microsurgery could be an invaluable way to
      translate laboratory data on liver research into new clinical diagnostic and
      therapeutic strategies.

PMID- 22855696
TI  - Life style modification improves insulin resistance and liver histology in
      patients with non-alcoholic fatty liver disease.
AB  - AIM: To study the effect of regular aerobic exercise on insulin resistance, serum
      aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD)
      patients. METHODS: Sixty (mean age 40.0 +/- 8.5 years, 75% male) NAFLD patients
      were included in the study. After baseline anthropometric measurement i.e., body
      mass index (BMI), waist circumference (WC); all patients were advised regular
      aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around
      70% of his maximal heart rate. In addition, moderately energy restricted diet was
      advised to patients with high BMI (> 25 kg/m(2)). Monthly follow up was done by
      measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase
      (ALT). Insulin resistance was calculated using homeostasis model assessment
      (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin
      resistance was arbitrarily considered altered when it was >= 2. Liver biopsy was
      done in a section of patients at baseline and after 6 mo. RESULTS: Seventy
      percent (42/60) patients were overweight or obese; 95% (57/60) had central
      obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant
      patients insulin resistance decreased from 6.4 +/- 6.1 to 1.3 +/- 1.0, BMI from
      26.7 +/- 3.3 kg/m(2) to 25.0 +/- 3.3 kg/m(2), WC from 95.7 +/- 8.9 cm to 90.8 +/-
      7.3 cm and ALT from 84.8 +/- 43.5 U/L to 41.3 +/- 18.2 U/L (P < 0.01). In 15
      exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show
      significant change at 6 mo follow up. Six of 8 patients in compliant group on
      repeat liver biopsy showed significant change in steatosis and necroinflammation.
      Nonalcoholic steatohepatitis scores improved form 5.3 +/- 1.5 to 3.35 +/- 1.5.
      The decline in insulin resistance correlated with decline in ALT (P = 0.01, r(s)
      = 0.90) and liver histology (P = 0.03, r(s) = 0.73). CONCLUSION: Life style
      modification improves insulin resistance resulting in improvement in ALT and
      liver histology in NAFLD patients.

PMID- 22855697
TI  - Prevalence and virological profiles of hepatitis B infection in human
      immunodeficiency virus patients.
AB  - AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human
      immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm(3)
      and without antiretroviral therapy; to describe different HBV-HIV coinfection
      virological profiles; and to search for factors associated with HBs antigen
      (HBsAg) presence in these HIV positive patients. METHODS: During four months
      (June through September 2006), 491 patients were received in four HIV positive
      monitoring clinical centers in Abidjan. INCLUSION CRITERIA: HIV-1 or HIV-1 and 2
      positive patients, age >= 18 years, CD4+ T-cell count < 500/mL and formal and
      signed consent of the patient. Realized blood tests included HIV serology, CD4+ T
      cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg
      and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti
      HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients.
      Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb
      positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg
      negative status and without anti-HBsAb. Univariate analysis (Pearson chi(2) test
      or Fischer exact test) and multivariate analysis (backward step-wise selection
      logistic regression) were performed as statistical analysis. RESULTS: Mean age of
      491 patients was 36 +/- 8.68 years and 73.3% were female. Type-1 HIV was found in
      97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO)
      clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172
      (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm(3)
      (interquartile range: 221-470). One hundred and twelve patients had less than 200
      CD4+ T-cell/mm(3). Plasma HIV-1 RNA load was elevated (>= 5 log(10) copies/mL) in
      221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and
      72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%),
      21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis
      (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection
      prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and
      detectable HBV DNA) was 21.3%. Three parameters were significantly associated
      with the presence of HBsAg: male [odds ratio (OR): 2.2; P = 0.005; 95% confidence
      interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2; P = 0.01; 95% CI: 1.3-7.9); and
      aspartate aminotransferase (AST) level higher than the standard (OR: 1.9; P =
      0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV
      positive patients. HBeAg positive chronic hepatitis and occult HBV infection are
      more frequent in HIV-positive patients than in HIV negative ones. Parameters
      associated with HBsAg positivity were male gender, AIDS status and increased AST
      level.

PMID- 22855698
TI  - Lifestyle intervention in non-alcoholic fatty liver disease in Chengyang
      District, Qingdao, China.
AB  - AIM: To evaluate the effect of a 6 and 12 mo lifestyle modification intervention
      in nonalcoholic fatty liver diseases (NAFLD) in Chengyang District of Qingdao.
      METHODS: Participants with NAFLD who had resided in Chengyang District for more
      than 5 years were enrolled in this study. After the 6 and 12 mo lifestyle
      modification intervention based on physical activity, nutrition and behavior
      therapy, parameters such as body weight, body mass index (BMI), waist
      circumference, serum alanine aminotransferase (ALT), aspartate aminotransferase
      values, serum cholesterol, triglycerides, fasting glucose, fasting insulin and
      visceral fat area (VFA), the liver-spleen ratio and the homeostasis model
      assessment of insulin resistance (HOMA-IR) were evaluated and compared between
      participants with and without the intervention. RESULTS: Seven hundred and twenty
      four participants were assigned to the lifestyle intervention group (LS) and 363
      participants were assigned to the control group (CON). After the intervention,
      body weights in the LS group were significantly decreased compared to those in
      the CON group at 6 mo (11.59% +/- 4.7% vs 0.4% +/- 0.2%, P = 0.001) and at 12 mo
      (12.73% +/- 5.6% vs 0.9% +/- 0.3%, P = 0.001). Compared with the CON group, BMI
      was more decreased in the LS group after 6 and 12 mo (P = 0.043 and P = 0.032).
      Waist circumference was more reduced in the LS group than in CON (P = 0.031 and P
      = 0.017). After the 6 and 12 mo intervention, ALT decreased significantly in the
      LS group (P = 0.003 and P = 0.002). After 6 and 12 mo, the metabolic syndrome
      rate had decreased more in the LS group compared with the CON group (P = 0.026
      and P = 0.017). After 12 mo, the HOMA-IR score decreased more obviously in the LS
      group (P = 0.041); this result also appeared in the VFA after 12 mo in the LS
      group (P = 0.035). CONCLUSION: Lifestyle intervention was effective in improving
      NAFLD in both 6 and 12 mo interventions. This intervention offered a practical
      approach for treating a large number of NAFLD patients in the Chengyang District
      of Qingdao.

PMID- 22855699
TI  - Herbal hepatoxicity from Chinese skullcap: A case report.
AB  - The use of herbal supplements has increased considerably over the last decade. We
      report a case of an elderly woman who began taking Move Free Advanced for
      arthritis, which in addition to glucosamine and chondroitin, contained two herbal
      ingredients, Chinese skullcap and Black Catechu. Our patient presented with
      significant cholestasis and hepatitis which significantly improved after
      discontinuation of the supplement. Since neither the patient nor the treating
      physician recognized this supplement as a potential hepatotoxin, she resumed
      taking the supplement and again suffered from considerable hepatotoxicity. Liver
      biopsy at that time was consistent with acute drug induced liver injury. She,
      once again, recovered after discontinuation of the supplement. Review of the
      literature confirms that Chinese skullcap has been implicated as a possible
      hepatotoxic agent which was demonstrated in this case.

PMID- 22855700
TI  - Acute autoimmune hepatitis mimicking metastatic liver disease: A case report.
AB  - We report progressive painless jaundice in a 39 year old female with a suspicion
      of metastatic liver disease on ultrasound and computed tomography scan of the
      abdomen. Although the most frequent liver lesions are liver metastasis because of
      dual blood supply of the liver and the impact of hormones, the index case proved
      to have acute autoimmune hepatitis (AIH) after liver biopsy was undertaken. AIH,
      an unresolving inflammation of liver, occurs predominantly among females
      worldwide. It may present acutely and even fulminant hepatitis has been
      described. The index case had a dramatic response to steroid treatment with total
      recovery and complete resolution of liver lesions. She is clinically fine and has
      been regularly attending our clinic for the last year. To our knowledge from a
      Medline search, this is the first report where AIH was seen to mimic metastatic
      liver disease.

PMID- 22855702
TI  - Overstimulation of newborn mice leads to behavioral differences and deficits in
      cognitive performance.
AB  - Observational studies in humans have found associations between overstimulation
      in infancy via excessive television viewing and subsequent deficits in cognition
      and attention. We developed and tested a mouse model of overstimulation whereby
      p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights)
      for six hours per day for a total of 42 days. 10 days later cognition and
      behavior were tested using the following tests: Light Dark Latency, Elevated Plus
      Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated
      mice performed significantly worse compared to controls suggesting increased
      activity and risk taking, diminished short term memory, and decreased cognitive
      function. These findings suggest that excessive non-normative stimulation during
      critical periods of brain development can have demonstrable untoward effects on
      subsequent neurocognitive function.

PMID- 22855703
TI  - Pseudogap temperature as a Widom line in doped Mott insulators.
AB  - The pseudogap refers to an enigmatic state of matter with unusual physical
      properties found below a characteristic temperature T* in hole-doped high
      temperature superconductors. Determining T* is critical for understanding this
      state. Here we study the simplest model of correlated electron systems, the
      Hubbard model, with cluster dynamical mean-field theory to find out whether the
      pseudogap can occur solely because of strong coupling physics and short nonlocal
      correlations. We find that the pseudogap characteristic temperature T* is a sharp
      crossover between different dynamical regimes along a line of thermodynamic
      anomalies that appears above a first-order phase transition, the Widom line. The
      Widom line emanating from the critical endpoint of a first-order transition is
      thus the organizing principle for the pseudogap phase diagram of the cuprates. No
      additional broken symmetry is necessary to explain the phenomenon. Broken
      symmetry states appear in the pseudogap and not the other way around.

PMID- 22855701
TI  - Interventions to Alleviate Symptoms Related to Breast Cancer Treatments and Areas
      of Needed Research.
AB  - Treatments for breast cancer produce a host of side effects, which can become
      debilitating. Some cancer treatment-related side effects occur in up to 90% of
      patients during treatment and can persist for months or years after treatment has
      ended. As the number of breast cancer survivors steadily increases, the need for
      cancer control intervention research to alleviate side effects also grows. This
      review provides a general overview of recent clinical research studies of
      selected topics in the areas of symptom management for breast cancer with a focus
      on cognitive difficulties, fatigue, cardiotoxicity, bone loss, insomnia, and
      cancer pain. We review both pharmacological and behavioral intervention clinical
      research studies, conducted with breast cancer patients and survivors.
      Additionally, clinical perspectives on symptom management and recommendations for
      areas of needed research are provided.

PMID- 22855704
TI  - The hOGG1Ser326Cys polymorphism and increased lung cancer susceptibility in
      Caucasians: an updated meta-analysis.
AB  - hOGG1 encodes a DNA repair enzyme responsible for the excision of reactive oxygen
      species (ROS) in damaged DNA. Previous studies have obtained inconsistent
      results. To validate the association between the hOGG1Ser326Cys polymorphism and
      lung cancer risk, we performed an updated meta-analysis of 20 studies (8739 cases
      and 10385 controls) using STATA version 11.1. With this approach, we tested the
      overall and subgroup association between the SNP and lung cancer susceptibility
      stratified by ethnicity, control sources, cell histotypes, and smoking status. We
      demonstrated a novel, significant correlation between the hOGG1 Ser326Cys
      polymorphism and increased lung cancer susceptibility in Caucasians. Our findings
      indicate a need for larger-scale studies to verify the association of this SNP
      with lung cancer risk in Caucasians.

PMID- 22307173
TI  - Recovery of H14 influenza A virus isolates from sea ducks in the Western
      Hemisphere.
AB  - In 2010, H14 influenza A viruses were recovered from clinically normal sea ducks
      in the United States. These are the first H14 isolates recovered in the Western
      Hemisphere and represent the only documented H14 influenza A viruses isolated
      since the original isolates were recovered from near the Caspian Sea during 1982.

PMID- 22855706
TI  - VDJ recombinase-mediated TCR beta locus gene usage and coding joint processing in
      peripheral T cells during perinatal and pediatric development.
AB  - The generation of TCR proteins is the result of V(D)J recombinase-mediated
      genomic rearrangements at recombination signal sequences (RSS) in human
      lymphocytes. V(D)J recombinase can also mediate rearrangements at nonimmune or
      "cryptic" RSS in normal and leukemic human peripheral T cells. We previously
      demonstrated age- and gender-specific developmental differences in V(D)J coding
      joint processing at cryptic RSS within the HPRT locus in peripheral T cells from
      healthy children (Murray et al. 2006. J. Immunol. 177: 5393-5404). In this study,
      we investigated developmentally specific V(D)J recombinase TCRbeta immune gene
      rearrangements and coding joint processing at RSS in peripheral T cells in the
      same pediatric population. This approach provided a unique opportunity to
      investigate site-specific V(D)J recombinase rearrangements and coding joint
      processing at immune and nonimmune genes from the same individual T cell
      population. We determined the genomic sequence of 244 TCRbeta coding junctions
      from 112 (63 male, 49 female) subjects from the late stages of fetal development
      through 9 y of age. We observed both age- and gender-specific V(D)J recombinase
      mediated TCRbeta gene usage and coding joint processing at immune RSS. To the
      best of our knowledge, these data represent the first description of age- and
      gender-specific developmental differences in TCR gene usage and coding joint
      processing that could directly influence TCR diversity and immune specificity. It
      will be important for future studies to ascertain the mechanistic etiology of
      these developmental and gender differences in TCR diversity and specificity, as
      well as their importance with respect to the age and gender risks for infectious
      and autoimmune diseases in humans.

PMID- 22855707
TI  - B cell memory to a serogroup C meningococcal conjugate vaccine in childhood and
      response to booster: little association with serum IgG antibody.
AB  - The maintenance of adequate serum Ab levels following immunization has been
      identified as the most important mechanism for individual long-term protection
      against rapidly invading encapsulated bacteria. The mechanisms for maintaining
      adequate serum Ab levels and the relationship between Ag-specific memory B cells
      and Ab at steady state are poorly understood. We measured the frequency of
      circulating serogroup C meningococcal (MenC)-specific memory B cells in 250
      healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming,
      before a booster of a combined Haemophilus influenzae type b-MenC conjugate
      vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the
      relationship between circulating MenC-specific memory B cell frequencies and Ab
      at baseline and following the booster vaccine. We found very low frequencies of
      circulating MenC-specific memory B cells at steady state in primary school-aged
      children and little association with MenC IgG Ab levels. Following vaccination,
      there were robust memory B cell booster responses that, unlike Ab levels, were
      not dependent on age at priming with MenC. Measurement of B cell memory in
      peripheral blood does not predict steady state Ab levels nor the capacity to
      respond to a booster dose of MenC Ag.

PMID- 22855708
TI  - Tissue-expressed B7x affects the immune response to and outcome of lethal
      pulmonary infection.
AB  - B7x (B7-H4 or B7S1), a member of the B7 family, inhibits in vitro T cell
      proliferation and cytokine production by binding to an unidentified receptor on
      activated T cells, but its in vivo function remains largely unclear. We show that
      B7x protein was expressed in epithelial cells of the lung, but not in lymphoid
      tissues. To investigate the role of B7x in the lung, we determined the
      susceptibility of B7x-deficient (B7x(-/-)) mice to a lethal pulmonary infection
      with Streptococcus pneumoniae. B7x(-/-), but not B7-H3-deficient, mice were
      significantly more resistant to S. pneumoniae pulmonary infection than their wild
      type (Wt) counterparts. B7x(-/-) mice had significantly lower bacterial burdens
      and levels of inflammatory cytokines in lungs as early as 12 h postinfection.
      They also had milder immunopathology that was localized in alveolar spaces,
      whereas Wt mice had severe inflammation that was perivascular. Control of
      infection in B7x(-/-) mice was associated with a marked increase in activated CD4
      and CD8 T cells and fewer neutrophils in lungs, whereas the susceptible Wt mice
      had the opposite cellular profile. In B7x(-/-)Rag1(-/-) mice that lack T cells,
      reduction in bacterial burden was no longer observed. Control of S. pneumoniae
      and the increased survival observed was specific to the lung, because
      systemically infected B7x(-/-) mice were not resistant to infection. These data
      indicate that lung-expressed B7x negatively regulates T cells, and that in its
      absence, in B7x(-/-) mice, an enhanced T cell response contributed to reduced
      lethality in a pulmonary infection model with S. pneumoniae.

PMID- 22855709
TI  - Identification of a catalytic exosite for complement component C4 on the serine
      protease domain of C1s.
AB  - The classical pathway of complement is crucial to the immune system, but it also
      contributes to inflammatory diseases when dysregulated. Binding of the C1 complex
      to ligands activates the pathway by inducing autoactivation of associated C1r,
      after which C1r activates C1s. C1s cleaves complement component C4 and then C2 to
      cause full activation of the system. The interaction between C1s and C4 involves
      active site and exosite-mediated events, but the molecular details are unknown.
      In this study, we identified four positively charged amino acids on the serine
      protease domain that appear to form a catalytic exosite that is required for
      efficient cleavage of C4. These residues are coincidentally involved in
      coordinating a sulfate ion in the crystal structure of the protease. Together
      with other evidence, this pointed to the involvement of sulfate ions in the
      interaction with the C4 substrate, and we showed that the protease interacts with
      a peptide from C4 containing three sulfotyrosine residues. We present a molecular
      model for the interaction between C1s and C4 that provides support for the above
      data and poses questions for future research into this aspect of complement
      activation.

PMID- 22855710
TI  - CD4+ T cells are necessary and sufficient to confer protection against Chlamydia
      trachomatis infection in the murine upper genital tract.
AB  - Chlamydia trachomatis infection is the most common bacterial sexually transmitted
      disease in the United States. Chlamydia infections that ascend to the upper
      genital tract can persist, trigger inflammation, and result in serious sequelae
      such as infertility. However, mouse models in which the vaginal vault is
      inoculated with C. trachomatis do not recapitulate the course of human disease.
      These intravaginal infections of the mouse do not ascend efficiently to the upper
      genital tract, do not cause persistent infection, do not induce significant
      inflammation, and do not induce significant CD4+ T cell infiltration. In this
      article, we describe a noninvasive transcervical infection model in which we
      bypass the cervix and directly inoculate C. trachomatis into the uterus. We show
      that direct C. trachomatis infection of the murine upper genital tract stimulates
      a robust Chlamydia-specific CD4+ T cell response that is both necessary and
      sufficient to clear infection and provide protection against reinfection.

PMID- 22855712
TI  - The development and function of memory regulatory T cells after acute viral
      infections.
AB  - Natural CD4+CD25+Foxp3+ regulatory T cells (Tregs) are critical for the control
      of immune responses to pathogens. However, most studies have focused on chronic
      infections, in which pathogen-specific Tregs contribute to pathogen persistence
      and, in some cases, concomitant immunity. How Tregs behave and function following
      acute infections remains largely unknown. In this article, we show that pathogen
      specific Tregs can be activated and expand upon acute viral infections in vivo.
      The activated Tregs then contract to form a memory pool after resolution of the
      infection. These memory Tregs expand rapidly upon a secondary challenge, secrete
      large amounts of IL-10, and suppress excessive immunopathological conditions
      elicited by recall expansion of non-Tregs via an IL-10-dependent mechanism. Our
      work reveals a memory Treg population that develops after acute viral infections
      and may help in the design of effective strategies to circumvent excessive
      immunopathological effects.

PMID- 22855713
TI  - Airway epithelial expression of TLR5 is downregulated in healthy smokers and
      smokers with chronic obstructive pulmonary disease.
AB  - The TLRs are important components of the respiratory epithelium host innate
      defense, enabling the airway surface to recognize and respond to a variety of
      insults in inhaled air. On the basis of the knowledge that smokers are more
      susceptible to pulmonary infection and that the airway epithelium of smokers with
      chronic obstructive pulmonary disease (COPD) is characterized by bacterial
      colonization and acute exacerbation of airway infections, we assessed whether
      smoking alters expression of TLRs in human small airway epithelium, the primary
      site of smoking-induced disease. Microarrays were used to survey the TLR family
      gene expression in small airway (10th to 12th order) epithelium from healthy
      nonsmokers (n = 60), healthy smokers (n = 73), and smokers with COPD (n = 36).
      Using the criteria of detection call of present (P call) >= 50%, 6 of 10 TLRs
      (TLRs 1-5 and 8) were expressed. Compared with nonsmokers, the most striking
      change was for TLR5, which was downregulated in healthy smokers (1.4-fold, p < 10
      10) and smokers with COPD (1.6-fold, p < 10-11). TaqMan RT-PCR confirmed these
      observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was
      expressed mainly on the apical side of the epithelium and was decreased in
      healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream
      genes, IL-6 and IL-8, was highly induced by flagellin in TLR5 high-expressing
      cells compared with TLR5 low-expressing cells. In the context that TLR5 functions
      to recognize pathogens and activate innate immune responses, the smoking-induced
      downregulation of TLR5 may contribute to smoking-related susceptibility to airway
      infection, at least for flagellated bacteria.

PMID- 22855711
TI  - Dendritic cell sphingosine 1-phosphate receptor-3 regulates Th1-Th2 polarity in
      kidney ischemia-reperfusion injury.
AB  - Dendritic cells (DCs) are central to innate and adaptive immunity of early kidney
      ischemia-reperfusion injury (IRI), and strategies to alter DC function may
      provide new therapeutic opportunities. Sphingosine 1-phosphate (S1P) modulates
      immunity through binding to its receptors (S1P1-5), and protection from kidney
      IRI occurs in S1P3-deficient mice. Through a series of experiments we determined
      that this protective effect was owing in part to differences between S1P3
      sufficient and -deficient DCs. Mice lacking S1P3 on bone marrow cells were
      protected from IRI, and S1P3-deficient DCs displayed an immature phenotype. Wild
      type (WT) but not S1P3-deficient DCs injected into mice depleted of DCs prior to
      kidney IR reconstituted injury. Adoptive transfer (i.e., i.v. injection) of
      glycolipid (Ag)-loaded WT but not S1P3-deficient DCs into WT mice exacerbated
      IRI, suggesting that WT but not S1P3-deficient DCs activated NKT cells. Whereas
      WT DC transfers activated the Th1/IFN-gamma pathway, S1P3-deficient DCs activated
      the Th2/IL-4 pathway, and an IL-4-blocking Ab reversed protection from IRI,
      supporting the concept that IL-4 mediates the protective effect of S1P3-deficient
      DCs. Administration of S1P3-deficient DCs 7 d prior to or 3 h after IRI protected
      mice from IRI and suggests their potential use in cell-based therapy. We conclude
      that absence of DC S1P3 prevents DC maturation and promotes a Th2/IL-4 response.
      These findings highlight the importance of DC S1P3 in modulating NKT cell
      function and IRI and support development of selective S1P3 antagonists for
      tolerizing DCs for cell-based therapy or for systemic administration for the
      prevention and treatment of IRI and autoimmune diseases.

PMID- 22855715
TI  - Rapid differentiation of monocytes into type I IFN-producing myeloid dendritic
      cells as an antiviral strategy against influenza virus infection.
AB  - Myeloid dendritic cells (mDCs) have long been thought to function as classical
      APCs for T cell responses. However, we demonstrate that influenza viruses induce
      rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the
      virus-induced mDCs failed to upregulate DC maturation markers and were unable to
      induce allogeneic lymphoproliferation. Virus-induced mDCs secreted little, if
      any, proinflammatory cytokines; however, they secreted a substantial amount of
      chemoattractants for monocytes (MCP-1 and IP-10). Interestingly, the
      differentiated mDCs secreted type I IFN and upregulated the expression of IFN
      stimulated genes (tetherin, IFITM3, and viperin), as well as cytosolic viral RNA
      sensors (RIG-I and MDA5). Additionally, culture supernatants from virus-induced
      mDCs suppressed the replication of virus in vitro. Furthermore, depletion of
      monocytes in a mouse model of influenza infection caused significant reduction of
      lung mDC numbers, as well as type I IFN production in the lung. Consequently,
      increased lung virus titer and higher mortality were observed. Taken together,
      our results demonstrate that the host responds to influenza virus infection by
      initiating rapid differentiation of circulating monocytes into IFN-producing
      mDCs, which contribute to innate antiviral immune responses.

PMID- 22855714
TI  - Systemic analysis of PPARgamma in mouse macrophage populations reveals marked
      diversity in expression with critical roles in resolution of inflammation and
      airway immunity.
AB  - Although peroxisome proliferator-activated receptor gamma (PPARgamma) has anti
      inflammatory actions in macrophages, which macrophage populations express
      PPARgamma in vivo and how it regulates tissue homeostasis in the steady state and
      during inflammation remains unclear. We now show that lung and spleen macrophages
      selectively expressed PPARgamma among resting tissue macrophages. In addition, Ly
      6C(hi) monocytes recruited to an inflammatory site induced PPARgamma as they
      differentiated to macrophages. When PPARgamma was absent in Ly-6C(hi)-derived
      inflammatory macrophages, initiation of the inflammatory response was unaffected,
      but full resolution of inflammation failed, leading to chronic leukocyte
      recruitment. Conversely, PPARgamma activation favored resolution of inflammation
      in a macrophage PPARgamma-dependent manner. In the steady state, PPARgamma
      deficiency in red pulp macrophages did not induce overt inflammation in the
      spleen. By contrast, PPARgamma deletion in lung macrophages induced mild
      pulmonary inflammation at the steady state and surprisingly precipitated
      mortality upon infection with Streptococcus pneumoniae. This accelerated
      mortality was associated with impaired bacterial clearance and inability to
      sustain macrophages locally. Overall, we uncovered critical roles for macrophage
      PPARgamma in promoting resolution of inflammation and maintaining functionality
      in lung macrophages where it plays a pivotal role in supporting pulmonary host
      defense. In addition, this work identifies specific macrophage populations as
      potential targets for the anti-inflammatory actions of PPARgamma agonists.

PMID- 22855716
TI  - Cutting edge: lymphoid tissue inducer cells maintain memory CD4 T cells within
      secondary lymphoid tissue.
AB  - Phylogeny shows that CD4 T cell memory and lymph nodes coevolved in placental
      mammals. In ontogeny, retinoic acid orphan receptor (ROR)gamma-dependent lymphoid
      tissue inducer (LTi) cells program the development of mammalian lymph nodes. In
      this study, we show that although primary CD4 T cell expansion is normal in
      RORgamma-deficient mice, the persistence of memory CD4 T cells is RORgamma
      dependent. Furthermore, using bone marrow chimeric mice we demonstrate that LTi
      cells are the key RORgamma-expressing cell type sufficient for memory CD4 T cell
      survival in the absence of persistent Ag. This effect was specific for CD4 T
      cells, as memory CD8 T cells survived equally well in the presence or absence of
      LTi cells. These data demonstrate a novel role for LTi cells, archetypal members
      of the innate lymphoid cell family, in supporting memory CD4 T cell survival in
      vivo.

PMID- 22855717
TI  - Screening of environmental samples for bacteria producing 1,3-propanediol from
      glycerol.
AB  - Twenty nine environmental samples were screened for the presence of anaerobic
      microorganisms fermenting glycerol with 1,3-propanediol as a final product. Seven
      samples were then selected for the next step of our research and eight bacteria
      strains were cultured anaerobically. Seven of them produced 1,3-propanediol with
      a yield of 0.47-0.58. Six of the the isolated microorganisms were then classified
      as Clostridium butyricum (four strains), C. lituseburense (one strain), and C.
      sartagoforme (one strain). We suggest that of all these strains C. butyricum
      2CR371.5 is the best 1,3-propanediol producer as producing no lactate as a by
      product and growing well on a glycerol-containing medium.

PMID- 22855718
TI  - 1,3-propanediol production by Escherichia coli expressing genes of dha operon
      from Clostridium butyricum  2CR371.5.
AB  - 1,3-propanediol is used as a monomer in the production of some polymers e.g.
      polytrimethylene terephthalate used in the production of carpets and textile
      fibers and in the thermoplastics engineering. However, the traditional chemical
      synthesis is expensive, generates some toxic intermediates and requires a
      reduction step under high hydrogen pressure. Biological production of 1,3
      propanediol could be an attractive alternative to the traditional chemical
      methods. Moreover, crude glycerol which is a by-product of biodiesel production,
      can be used. We constructed a recombinant Escherichia coli strain producing 1,3
      propanediol from glycerol by introducing  genes of the dha operon from
      Clostridium butyricum 2CR371.5, a strain from our collection of environmental
      samples and strains. The E. coli strain produced 3.7 g of 1,3-propanediol per one
      litre of culture with the yield of 0.3 g per 1 g of glycerol consumed.

PMID- 22855719
TI  - Placental prostate-specific antigen content in preeclampsia.
AB  - Preeclampsia is a multisystem disorder that can manifest clinically with
      hypertension and proteinuria. Previous studies reported the presence of placental
      PSA in normal pregnancy but no study has been done in preeclampsia. The aim of
      this study was to investigate PSA content in preeclampsia. Preeclampsia was
      diagnosed according to the American College of Obstetricians and Gynecologists
      criteria. Placentas were obtained from 33 preeclamptic and 34 normotensive women.
      Placenta samples were homogenized and the supernatants were immediately analyzed.
      The tissue PSA content was measured by Immulite 2000 PSA assay. The data were
      analyzed with Student's t-test and Pearson correlation test. There was a
      significant difference in placental PSA content between preeclamptic and
      normotensive women. Placental content of PSA was higher in the preeclamptic group
      with intrauterine growth restriction (IUGR) than in the preeclamptic and
      normotensive pregnant without IUGR groups. No significant difference was found in
      this respect between preeclamptic and normotensive women without IUGR. In
      conclusion, we found that placental PSA content is elevated in preeclampsia and
      negatively correlated with infant birth weight. Further studies will be necessary
      to define the roles of PSA more precisely and to examine its effects on the
      pathophysiology of preeclampsia.

PMID- 22855720
TI  - NF-kappaB signaling pathway and free radical impact.
AB  - The activation of NF-kappaB transcription factor is critical for a wide range of
      processes such as immunity, inflammation, cell development, growth and survival.
      It is activated by a variety of stimuli including cytokines, ionizing radiation
      and oxidative stress. Redox modulations of NF-kappaB pathway have been widely
      demonstrated. Studies carried out during last years have advanced our knowledge
      about possible connections between NF-kappaB pathway and the impact of free
      radicals. This review is an endeavor to gather recent results focused on this
      issue, although an important question, whether oxidative stress plays a
      physiological role in NF-kappaB activation, seems to be still unanswered.

PMID- 22855721
TI  - Signaling mechanisms controlling cell fate and embryonic patterning.
AB  - During development, signaling pathways specify cell fates by activating
      transcriptional programs in response to extracellular signals. Extensive studies
      in the past 30 years have revealed that surprisingly few pathways exist to
      regulate developmental programs and that dysregulation of these can lead to human
      diseases, including cancer. Although these pathways use distinct signaling
      components and signaling strategies, a number of common themes have emerged
      regarding their organization and regulation in time and space. Examples from
      Drosophila, such as Notch, Hedgehog, Wingless/WNT, BMP (bone morphogenetic
      proteins), EGF (epidermal growth factor), and FGF (fibroblast growth factor)
      signaling, illustrate their abilities to act either at a short range or over a
      long distance, and in some instances to generate morphogen gradients that pattern
      fields of cells in a concentration-dependent manner. They also show how feedback
      loops and transcriptional cascades are part of the logic of developmental
      regulation.

PMID- 22855722
TI  - Dendritic cells: arbiters of immunity and immunological tolerance.
AB  - Dendritic cells (DCs) link innate immune sensing of the environment to the
      initiation of adaptive immune responses. Given their supreme capacity to interact
      with and present antigen to T cells, DCs have been proposed as key mediators of
      immunological tolerance in the steady state. However, recent evidence suggests
      that the role of DCs in central and peripheral T-cell tolerance is neither
      obligate nor dominant. Instead, DCs appear to regulate multiple aspects of T-cell
      physiology including tonic antigen receptor signaling, priming of effector T-cell
      response, and the maintenance of regulatory T cells. These diverse contributions
      of DCs may reflect the significant heterogeneity and "division of labor" observed
      between and within distinct DC subsets. The emerging complex role of different DC
      subsets should form the conceptual basis of DC-based therapeutic approaches
      toward induction of tolerance or immunization.

PMID- 22855723
TI  - Pluripotency in the embryo and in culture.
AB  - Specific cells within the early mammalian embryo have the capacity to generate
      all somatic lineages plus the germline. This property of pluripotency is confined
      to the epiblast, a transient tissue that persists for only a few days. In vitro,
      however, pluripotency can be maintained indefinitely through derivation of stem
      cell lines. Pluripotent stem cells established from the newly formed epiblast are
      known as embryonic stem cells (ESCs), whereas those generated from later stages
      are called postimplantation epiblast stem cells (EpiSCs). These different classes
      of pluripotent stem cell have distinct culture requirements and gene expression
      programs, likely reflecting the dynamic development of the epiblast in the
      embryo. In this chapter we review current understanding of how the epiblast forms
      and relate this to the properties of derivative stem cells. We discuss whether
      ESCs and EpiSCs are true counterparts of different phases of epiblast development
      or are culture-generated phenomena. We also consider the proposition that early
      epiblast cells and ESCs may represent a naive ground state without any
      prespecification of lineage choice, whereas later epiblasts and EpiSCs may be
      primed in favor of particular fates.

PMID- 22855724
TI  - Molecular mechanisms of inner ear development.
AB  - The inner ear is a structurally complex vertebrate organ built to encode sound,
      motion, and orientation in space. Given its complexity, it is not surprising that
      inner ear dysfunction is a relatively common consequence of human genetic
      mutation. Studies in model organisms suggest that many genes currently known to
      be associated with human hearing impairment are active during embryogenesis.
      Hence, the study of inner ear development provides a rich context for
      understanding the functions of genes implicated in hearing loss. This chapter
      focuses on molecular mechanisms of inner ear development derived from studies of
      model organisms.

PMID- 22855725
TI  - The role of apoptosis-induced proliferation for regeneration and cancer.
AB  - Genes dedicated to killing cells must have evolved because of their positive
      effects on organismal survival. Positive functions of apoptotic genes have been
      well established in a large number of biological contexts, including their role
      in eliminating damaged and potentially cancerous cells. More recently, evidence
      has suggested that proapoptotic proteins-mostly caspases-can induce proliferation
      of neighboring surviving cells to replace dying cells. This process, that we will
      refer to as "apoptosis-induced proliferation," may be critical for stem cell
      activity and tissue regeneration. Depending on the caspases involved, at least
      two distinct types of apoptosis-induced proliferation can be distinguished. One
      of these types have been studied using a model in which cells have initiated cell
      death, but are prevented from executing it because of effector caspase
      inhibition, thereby generating "undead" cells that emit persistent mitogen
      signaling and overgrowth. Such conditions are likely to contribute to certain
      forms of cancer. In this review, we summarize the current knowledge of apoptosis
      induced proliferation and discuss its relevance for tissue regeneration and
      cancer.

PMID- 22855727
TI  - On mammary gland growth factors: roles in normal development and in cancer.

PMID- 22855726
TI  - Spatio-temporal organization of replication in bacteria and eukaryotes (nucleoids
      and nuclei).
AB  - Here we discuss the spatio-temporal organization of replication in eubacteria and
      eukaryotes. Although there are significant differences in how replication is
      organized in cells that contain nuclei from those that do not, you will see that
      organization of replication in all organisms is principally dictated by the
      structured arrangement of the chromosome. We will begin with how replication is
      organized in eubacteria with particular emphasis on three well studied model
      organisms. We will then discuss spatial and temporal organization of replication
      in eukaryotes highlighting the similarities and differences between these two
      domains of life.

PMID- 22855728
TI  - On cell-matrix interactions in mammary gland development and breast cancer.

PMID- 22855729
TI  - Protein folding and quality control in the ER.

PMID- 22855730
TI  - GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in
      congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive
      K+ channel.
AB  - Infants with congenital hyperinsulinism owing to inactivating mutations in the
      K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require
      pancreatectomy to control the hypoglycemia. In preclinical studies, we showed
      that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion
      and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was
      to examine the effects of exendin-(9-39) on fasting blood glucose in subjects
      with K(ATP)HI. This was a randomized, open-label, two-period crossover pilot
      clinical study. Nine subjects with K(ATP)HI received either exendin-(9-39) or
      vehicle on two different days. The primary outcome was blood glucose; secondary
      outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood
      glucose and glucose area under the curve were significantly increased by exendin
      (9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39)
      infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not
      affected by treatment. In addition, exendin-(9-39) significantly inhibited amino
      acid-stimulated insulin secretion in pancreatic islets isolated from neonates
      with K(ATP)HI. Our findings have two important implications: 1) GLP-1 and its
      receptor play a role in the regulation of fasting glycemia in K(ATP)HI; and 2)
      the GLP-1 receptor may be a therapeutic target for the treatment of children with
      K(ATP)HI.

PMID- 22855732
TI  - Cardiovascular events after bariatric surgery in obese subjects with type 2
      diabetes.
AB  - OBJECTIVE: Obese individuals with type 2 diabetes have an increased risk of
      cardiovascular disease. The effect of bariatric surgery on cardiovascular events
      in obese individuals with type 2 diabetes remains to be determined. The Swedish
      Obese Subjects (SOS) study is a prospective, controlled intervention study that
      examines the effects of bariatric surgery on hard end points. The aim of the
      present study was to examine the effect of bariatric surgery on cardiovascular
      events in the SOS study participants with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: All SOS study participants with type 2 diabetes at baseline were
      included in the analyses (n = 345 in the surgery group and n = 262 in the control
      group). Mean follow-up was 13.3 years (interquartile range 10.2-16.4) for all
      cardiovascular events. RESULTS: Bariatric surgery was associated with a reduced
      myocardial infarction incidence (38 events among the 345 subjects in the surgery
      group vs. 43 events among the 262 subjects in the control group; log-rank P =
      0.017; adjusted hazard ratio [HR] 0.56 [95% CI 0.34-0.93]; P = 0.025). No effect
      of bariatric surgery was observed on stroke incidence (34 events among the 345
      subjects in the surgery group vs. 24 events among the 262 subjects in the control
      group; log-rank P = 0.852; adjusted HR 0.73 [0.41-1.30]; P = 0.29). The effect of
      surgery in reducing myocardial infarction incidence was stronger in individuals
      with higher serum total cholesterol and triglycerides at baseline (interaction P
      value = 0.02 for both traits). BMI (interaction P value = 0.12) was not related
      to the surgery outcome. CONCLUSIONS: Bariatric surgery reduces the incidence of
      myocardial infarction in obese individuals with type 2 diabetes. Preoperative BMI
      should be integrated with metabolic parameters to maximize the benefits of
      bariatric surgery.

PMID- 22855731
TI  - The influence of type 1 and type 2 diabetes on periodontal disease progression:
      prospective results from the Study of Health in Pomerania (SHIP).
AB  - OBJECTIVE: To explore associations between diabetes etiology (type 1 diabetes
      mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year
      periodontal status change. RESEARCH DESIGN AND METHODS: The Study of Health in
      Pomerania (SHIP) is a population-based stratified sample of German men and women.
      Healthy participants and those determined to have T2DM arose from the SHIP
      cohort, and T1DM participants were recruited from diabetes clinics in the
      catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53%
      women; 20-81 years of age) were included. Diabetes was determined via physician
      diagnosis and/or HbA(1c) >=6.5% (uncontrolled diabetes >7.0%). Examiners blinded
      to diabetes status performed random half-mouth periodontal examinations,
      assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at
      baseline and follow-up. Participants were categorized into six groups as follows:
      1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n =
      80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6)
      uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change
      (DeltaMPD), mean AL change (DeltaMAL), or incident tooth-loss values were
      regressed across the aforementioned diabetes categories. RESULTS: Mean (SD)
      DeltaMPD and DeltaMAL values among all participants were -0.08 +/- 0.5 mm and
      0.08 +/- 1.03 mm, respectively, and 34% lost one or more teeth. Relative to
      diabetes-free participants, those with uncontrolled T2DM experienced greater
      DeltaMPD +/- SE (P < 0.05), whereas participants with either uncontrolled T1DM or
      uncontrolled T2DM realized greater DeltaMAL (P < 0.05). Uncontrolled T1DM and
      T2DM were both associated with an increased risk of future tooth loss (P < 0.05).
      CONCLUSIONS: Diabetes control, but not etiology, was associated with future tooth
      loss and accelerated AL progression.

PMID- 22855733
TI  - Low hemoglobin A(1c) in nondiabetic adults: an elevated risk state?
AB  - OBJECTIVE: To identify predictors of low hemoglobin A(1c) (HbA(1c)) (<5.0%) and
      to investigate the association of low HbA(1c) with cause-specific mortality and
      risk of liver disease hospitalization. RESEARCH DESIGN AND METHODS: Prospective
      cohort study of 13,288 participants in the Atherosclerosis Risk in Communities
      Study. Logistic regression was used to identify cross-sectional correlates of low
      HbA(1c), and Cox proportional hazards models were used to estimate the
      association of low HbA(1c) with cause-specific mortality. RESULTS: Compared with
      participants with HbA(1c) in the normal range (5.0 to <5.7%), participants with
      low HbA(1c) were younger, less likely to smoke, had lower BMI, lower white cell
      count and fibrinogen levels, and lower prevalence of hypercholesterolemia and
      history of coronary heart disease. However, this group was more likely to have
      anemia and had a higher mean corpuscular volume. In adjusted Cox models with
      HbA(1c) of 5.0 to <5.7% as the reference group, HbA(1c) <5.0% was associated with
      a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.32,
      95% CI: 1.13-1.55) and of cancer death (1.47, 95% CI: 1.16-1.84). We also noted
      nonsignificant trends toward increased risk of death from cardiovascular causes
      (1.27, 95% CI: 0.93-1.75) and respiratory causes (1.42, 95% CI: 0.78-2.56). There
      was a J-shaped association between HbA(1c) and risk of liver disease
      hospitalization. CONCLUSIONS: No single cause of death appeared to drive the
      association between low HbA(1c) and total mortality. These results add to
      evidence that low HbA(1c) values may be a generalized marker of mortality risk in
      the general population.

PMID- 22855735
TI  - The role of a basolateral transporter in rosuvastatin transport and its interplay
      with apical breast cancer resistance protein in polarized cell monolayer systems.
AB  - Membrane transporters can play a clinically important role in drug absorption and
      disposition; Caco-2 and Madin-Darby canine kidney (MDCK) cells are the most
      widely used in vitro models for studying the functions of these transporters and
      associated drug interactions. Transport studies using these cell models are
      mostly focused on apical transporters, whereas basolateral drug transport
      processes are largely ignored. However, for some hydrophilic drugs, a basolateral
      uptake transporter may be required for drugs to enter cells before they can
      interact with apical efflux transporters. The objective of this study was to
      evaluate potential differences in drug transport across Caco-2 and MDCK
      basolateral membrane that could cause discrepancy in the identification of efflux
      transporter substrates and to elucidate the underlying factors that may cause
      such differences, using rosuvastatin as a model substrate. Bidirectional
      transport results in Caco-2 and breast cancer resistance protein-MDCK cells
      demonstrated the necessity of an uptake transporter at the basolateral membrane
      for rosuvastatin. Kinetic study revealed saturable and nonsaturable processes for
      rosuvastatin uptake across the Caco-2 basolateral membrane, with the saturable
      process encompassing >75% of overall rosuvastatin basolateral uptake at
      concentrations below the K(m) (4.2 MUM). Furthermore, rosuvastatin basolateral
      transport exhibited cis-inhibition and trans-stimulation phenomena, indicating a
      facilitated diffusion mechanism. This basolateral transporter appeared to be a
      prerequisite for rosuvastatin and perhaps for other hydrophilic substrates to
      interact with apical efflux transporters. Deficit of such a basolateral
      transporter in certain cell models may lead to false-negative results when
      screening drug interactions with apical efflux transporters.

PMID- 22855734
TI  - Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in
      children with DEND-associated mutations and may be improved by early treatment
      with sulfonylureas.
AB  - OBJECTIVE: To assess performance on an age-standardized neuromotor coordination
      task among sulfonylurea-treated KCNJ11-related neonatal diabetic patients.
      RESEARCH DESIGN AND METHODS: Nineteen children carrying KCNJ11 mutations
      associated with isolated diabetes (R201H; n = 8), diabetes with
      neurodevelopmental impairment (V59M or V59A [V59M/A]; n = 8), or diabetes not
      consistently associated with neurodevelopmental disability (Y330C, E322K, or
      R201C; n = 3) were studied using the age-standardized Beery-Buktenica
      Developmental Test of Visual-Motor Integration (VMI). RESULTS: Although R201H
      subjects tested in the normal range (median standard score = 107), children with
      V59M/A mutations had significantly lower than expected VMI standard scores
      (median = 49). The scores for all three groups were significantly different from
      each other (P = 0.0017). The age of sulfonylurea initiation was inversely
      correlated with VMI scores in the V59M/A group (P < 0.05). CONCLUSIONS:
      Neurodevelopmental disability in KCNJ11-related diabetes includes visuomotor
      problems that may be ameliorated by early sulfonylurea treatment. Comprehensive
      longitudinal assessment on larger samples will be imperative.

PMID- 22855736
TI  - Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to
      induce cholesterol efflux from human macrophage foam cells.
AB  - HDL particles may enter atherosclerotic lesions having an acidic intimal fluid.
      Therefore, we investigated whether acidic pH would affect their structural and
      functional properties. For this purpose, HDL(2) and HDL(3) subfractions were
      incubated for various periods of time at different pH values ranging from 5.5 to
      7.5, after which their protein and lipid compositions, size, structure, and
      cholesterol efflux capacity were analyzed. Incubation of either subfraction at
      acidic pH induced unfolding of apolipoproteins, which was followed by release of
      lipid-poor apoA-I and ensuing fusion of the HDL particles. The acidic pH-modified
      HDL particles exhibited an enhanced ability to promote cholesterol efflux from
      cholesterol-laden primary human macrophages. Importantly, treatment of the acidic
      pH-modified HDL with the mast cell-derived protease chymase completely depleted
      the newly generated lipid-poor apoA-I, and prevented the acidic pH-dependent
      increase in cholesterol efflux. The above-found pH-dependent structural and
      functional changes were stronger in HDL(3) than in HDL(2). Spontaneous acidic pH
      induced remodeling of mature spherical HDL particles increases HDL-induced
      cholesterol efflux from macrophage foam cells, and therefore may have
      atheroprotective effects.

PMID- 22855738
TI  - Moral transhumanism: the next step.
AB  - Although transhumanism offers hope for the transcendence of human biological
      limitations, it generates many intrinsic and consequential ethical concerns. The
      latter include issues such as the exacerbation of social inequalities and the
      exponentially increasing technological capacity to cause harm. To mitigate these
      risks, many thinkers have initiated investigations into the possibility of moral
      enhancement that could limit the power disparities facilitated by
      biotechnological enhancement. The arguments often focus on whether moral
      enhancement is morally permissible, or even obligatory, and remain largely in the
      realm of the hypothetical. This paper proposes that psilocybin may represent a
      viable, practical option for moral enhancement and that its further research in
      the context of moral psychology could comprise the next step in the development
      of moral transhumanism.

PMID- 22855737
TI  - Kinetic analysis of thermal stability of human low density lipoproteins: a model
      for LDL fusion in atherogenesis.
AB  - Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we
      showed that thermal denaturation mimics LDL remodeling and fusion, and revealed
      kinetic origin of LDL stability. Here we report the first quantitative analysis
      of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat
      denaturation, which is unique among lipoproteins, suggesting that fusion is
      preceded by other structural changes. High activation energy of denaturation,
      E(a) = 100 +/- 8 kcal/mol, indicates disruption of extensive packing interactions
      in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and
      negative-stain electron microscopy suggest that LDL dimerization is an early step
      in thermally induced fusion. Monoclonal antibody binding suggests possible
      involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion
      accelerates at pH < 7, which may contribute to LDL retention in acidic
      atherosclerotic lesions. Fusion also accelerates upon increasing LDL
      concentration in near-physiologic range, which likely contributes to
      atherogenesis. Thermal stability of LDL decreases with increasing particle size,
      indicating that the pro-atherogenic properties of small dense LDL do not result
      from their enhanced fusion. Our work provides the first kinetic approach to
      measuring LDL stability and suggests that lipid-lowering therapies that reduce
      LDL concentration but increase the particle size may have opposite effects on LDL
      fusion.

PMID- 22855739
TI  - Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker
      for unstable atherosclerosis.
AB  - AIMS: For the characterization of endothelial progenitor cells (EPCs), commonly
      the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent
      more immature 'early' progenitors. In patients with coronary artery disease
      (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN),
      which may mediate vascular calcification and abnormal repair. The aim of this
      study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk
      factors (RFs) and a history of stable (history of stenting/coronary artery bypass
      grafting) or unstable CAD (myocardial infarction). METHODS AND RESULTS: Medical
      history and blood samples from 282 patients (age 58 +/- 16 years) with CAD or at
      least one RF (mean 2.5 +/- 1.5) were analysed. For the analysis of EPC markers
      (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear
      cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts
      [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n =
      199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in
      those with a history of unstable CAD (n = 26; P < 0.001). The association with
      unstable CAD remained highly significant even after multivariate adjusting for
      RFs and the different characteristics of the groups. Osteocalcin positive 'early'
      EPCs trend to predict further events [HR for each doubling of the cell number:
      1.20 (95% CI: 1.00-1.46), P = 0.06]. CONCLUSION: Circulating OCN+ 'early' EPCs
      are strongly associated with unstable CAD. Therefore, this particular subset of
      EPCs could mediate abnormal vascular repair and may help identifying patients
      with a more unstable phenotype of atherosclerosis.

PMID- 22855740
TI  - Real-time MRI-guided right heart catheterization in adults using passive
      catheters.
AB  - AIMS: Real-time MRI creates images with superb tissue contrast that may enable
      radiation-free catheterization. Simple procedures are the first step towards
      novel interventional procedures. We aim to perform comprehensive transfemoral
      diagnostic right heart catheterization in an unselected cohort of patients
      entirely using MRI guidance. METHODS AND RESULTS: We performed X-ray and MRI
      guided transfemoral right heart catheterization in consecutive patients
      undergoing clinical cardiac catheterization. We sampled both cavae and both
      pulmonary arteries. We compared success rate, time to perform key steps, and
      catheter visibility among X-ray and MRI procedures using air-filled or gadolinium
      filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with
      coronary artery disease, three with other) underwent paired X-ray and MRI
      catheterization. Complete guidewire-free catheterization was possible in 15 of 16
      under both. MRI using gadolinium-filled balloons was at least as successful as X
      ray in all procedure steps, more successful than MRI using air-filled balloons,
      and better than both in entering the left pulmonary artery. Total catheterization
      time and individual procedure steps required approximately the same amount of
      time irrespective of image guidance modality. Catheter conspicuity was best under
      X-ray and next-best using gadolinium-filled MRI balloons. CONCLUSION: In this
      early experience, comprehensive transfemoral right heart catheterization appears
      feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters
      were more conspicuous than air-filled ones. Further workflow and device
      enhancement are necessary for clinical adoption.

PMID- 22855743
TI  - Embryonic protein nodal promotes breast cancer vascularization.
AB  - Tumor vascularization is requisite for breast cancer progression, and high
      microvascular density in tumors is a poor prognostic indicator. Patients bearing
      breast cancers expressing human embryonic stem cell (hESC)-associated genes
      similarly exhibit high mortality rates, and the expression of embryonic proteins
      is associated with tumor progression. Here, we show that Nodal, a hESC-associated
      protein, promotes breast cancer vascularization. We show that high levels of
      Nodal are positively correlated with high vascular densities in human breast
      lesions (P = 0.0078). In vitro, we show that Nodal facilitates breast cancer
      induced endothelial cell migration and tube formation, largely by upregulating
      the expression and secretion of proangiogenic factors by breast cancer cells.
      Using a directed in vivo angiogenesis assay and a chick chorioallantoic membrane
      assay, we show that Nodal promotes vascular recruitment in vivo. In a clinically
      relevant in vivo model, whereby Nodal expression was inhibited following tumor
      formation, we found a significant reduction in tumor vascularization concomitant
      with elevated hypoxia and tumor necrosis. These findings establish Nodal as a
      potential target for the treatment of breast cancer angiogenesis and progression.

PMID- 22855742
TI  - Autoregulatory mechanisms of phosphorylation of checkpoint kinase 1.
AB  - Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, is centrally
      involved in cell-cycle checkpoints and cellular response to DNA damage.
      Phosphorylation of Chk1 at 2 Ser/Gln (SQ) sites, Ser-317 and Ser-345, by the
      upstream kinase ATR is critical for checkpoint activation. However, the precise
      molecular mechanisms controlling Chk1 phosphorylation and subsequent checkpoint
      activation are not well understood. Here, we report unique autoregulatory
      mechanisms that control protein phosphorylation of human Chk1, as well as
      checkpoint activation and cell viability. Phosphorylation of Ser-317 is required,
      but not sufficient, for maximal phosphorylation at Ser-345. The N-terminal kinase
      domain of Chk1 prevents Chk1 phosphorylation at the C-terminus by ATR in the
      absence of DNA damage. Loss of the inhibitory effect imposed by the N-terminus
      causes constitutive phosphorylation of Chk1 by ATR under normal growth
      conditions, which in turn triggers artificial checkpoints that suppress the S
      phase progression. Furthermore, two point mutations were identified that rendered
      Chk1 constitutively active, and expression of the constitutively active mutant
      form of Chk1 inhibited cancer cell proliferation. Our findings therefore reveal
      unique regulatory mechanisms of Chk1 phosphorylation and suggest that expression
      of constitutively active Chk1 may represent a novel strategy to suppress tumor
      growth. Cancer Res; 72(15); 3786-94. (c)2012 AACR.

PMID- 22855744
TI  - Strongyloides pneumonia.

PMID- 22855746
TI  - Rapid implementation of new TB diagnostic tests: is it too soon for a global roll
      out of Xpert MTB/RIF?
AB  - In 2011 the World Health Organization approved Xpert MTB/RIF for tuberculosis
      diagnosis and recommended its rapid implementation. Xpert MTB/RIF is accurate:
      sensitivity is 72.5 -98.2% (smear-negative and -positive cases, respectively) and
      specificity 99.2%. Benefits include same-day diagnosis and simultaneous detection
      of rifampicin resistance. However, the test has some shortcomings and has not had
      time for thorough evaluation. Cost-effectiveness studies are difficult to perform
      and few have been completed. Existing data suggest cost-effectiveness in some,
      but not all, settings. The urgent need for better diagnostics is evident. Yet,
      serial implementation of new technologies causes ineffective spending and
      fragmentation of services. How new tests are incorporated into existing
      diagnostic algorithms affects both outcomes and costs. More detailed data on
      performance, effect on patient-important outcomes, and costs when used with
      adjunct tests are needed for each setting before implementation. While awaiting
      further clarification it seems prudent to slow its implementation among resource
      constrained tuberculosis control programs.

PMID- 22855747
TI  - Transforming TB diagnosis: can patients and control programs afford to wait?

PMID- 22855748
TI  - Resistance to rabies.

PMID- 22855749
TI  - Evidence of rabies virus exposure among humans in the Peruvian Amazon.
AB  - In May of 2010, two communities (Truenococha and Santa Marta) reported to be at
      risk of vampire bat depredation were surveyed in the Province Datem del Maranon
      in the Loreto Department of Peru. Risk factors for bat exposure included age less
      than or equal to 25 years and owning animals that had been bitten by bats. Rabies
      virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human
      sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG)
      antibodies were detected in the sera of three individuals, two of whom were also
      seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one
      respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent
      with positive rVNA results reported prior vaccination and 86% (six of seven) of
      rVNA-positive respondents reported being bitten by bats, these data suggest
      nonfatal exposure of persons to rabies virus, which is likely associated with
      vampire bat depredation.

PMID- 22855750
TI  - Drug coverage surveys for neglected tropical diseases: 10 years of field
      experience.
AB  - Mass drug administration is one of the public health strategies recommended by
      the World Health Organization for the control and elimination of seven neglected
      tropical diseases (NTDs). Because adequate coverage is vital to achieve program
      goals, periodically conducting surveys to validate reported coverage to guide NTD
      programs is recommended. Over the past decade, the Centers for Disease Control
      and Prevention (CDC) and collaborators conducted more than 30 two-stage cluster
      household surveys across three continents. The questionnaires gathered coverage
      data and information relevant to improving NTD programs including NTD-related
      attitudes and practices. From the 37 coverage survey estimates obtained in those
      surveys, 73.3% indicated an over reporting of coverage, including all three that
      assessed school-based distributions. It took an average of 1 week to conduct a
      survey. Our experiences led us to conclude that coverage surveys are useful and
      feasible tools to ensure NTD elimination and control goals are reached.

PMID- 22855751
TI  - Emerging nucleic acid-based tests for point-of-care detection of malaria.
AB  - Malaria remains a serious disease in the developing world. There is a growing
      consensus that new diagnostics are needed in low-resource settings. The ideal
      malaria diagnostic should be able to speciate; measure parasitemia; low-cost,
      quick, and simple to use; and capable of detecting low-level infections. A
      promising development are nucleic acid tests (NATs) for the diagnosis of malaria,
      which are well suited for point-of-care use because of their ability to detect
      low-level infections and speciate, and because they have high sensitivity and
      specificity. The greatest barrier to NAT use in the past has been its relatively
      high cost, and the amount of infrastructure required in the form of equipment,
      stable power, and reagent storage. This review describes recent developments to
      decrease the cost and run time, and increase the ease of use of NAT while
      maintaining their high sensitivity and specificity and low limit of detection at
      the point-of-care.

PMID- 22855752
TI  - Artemisinin-resistant malaria: research challenges, opportunities, and public
      health implications.
AB  - Artemisinin-based combination therapies are the most effective drugs to treat
      Plasmodium falciparum malaria. Reduced sensitivity to artemisinin monotherapy,
      coupled with the emergence of parasite resistance to all partner drugs, threaten
      to place millions of patients at risk of inadequate treatment of malaria.
      Recognizing the significance and immediacy of this possibility, the Fogarty
      International Center and the National Institute of Allergy and Infectious
      Diseases of the U.S. National Institutes of Health convened a conference in
      November 2010 to bring together the diverse array of stakeholders responding to
      the growing threat of artemisinin resistance, including scientists from malarious
      countries in peril. This conference encouraged and enabled experts to share their
      recent unpublished data from studies that may improve our understanding of
      artemisinin resistance. Conference sessions addressed research priorities to
      forestall artemisinin resistance and fostered collaborations between field- and
      laboratory-based researchers and international programs, with the aim of
      translating new scientific evidence into public health solutions. Inspired by
      this conference, this review summarizes novel findings and perspectives on
      artemisinin resistance, approaches for translating research data into relevant
      public health information, and opportunities for interdisciplinary collaboration
      to combat artemisinin resistance.

PMID- 22855753
TI  - Insecticide-treated plastic sheeting for emergency malaria prevention and shelter
      among displaced populations: an observational cohort study in a refugee setting
      in Sierra Leone.
AB  - A double-blind phase III malaria prevention trial was conducted in two refugee
      camps using pre-manufactured insecticide-treated plastic sheeting (ITPS) or
      untreated polyethylene sheeting (UPS) randomly deployed to defined sectors of
      each camp. In Largo camp the ITPS or UPS was attached to inner walls and ceilings
      of shelters, whereas in Tobanda the ITPS or UPS was used to line only the ceiling
      and roof. In Largo the Plasmodium falciparum incidence rate in children up to 3
      years of age who were cleared of parasites and monitored for 8 months was 163/100
      person-years under UPS and 63 under ITPS (adjusted odds ratio [AOR] = 0.40, 95%
      confidence interval [CI] = 0.33-0.47). In Tobanda incidence was 157/100 person
      years under UPS and 134 under ITPS (AOR = 0.85, 95% CI = 0.75-0.95). Protective
      efficacy was 61% under fully lined ITPS and 15% under roof lined ITPS. Anemia
      rates improved under ITPS in both camps. This novel tool proved to be a
      convenient, safe, and long-lasting method of malaria control when used as a full
      shelter lining in an emergency setting.

PMID- 22855754
TI  - Intralesional meglumine antimoniate for treatment of cutaneous leishmaniasis
      patients with contraindication to systemic therapy from Rio de Janeiro (2000 to
      2006).
AB  - We evaluated the effectiveness and safety of intralesional meglumine antimoniate
      (MA) in 24 not submitted to previous treatment patients with cutaneous
      leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment
      consisted of one to four intralesional applications of MA at 15-day intervals.
      Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional
      treatment in the absence of any relevant toxicity was successful in 20 (83.3%)
      patients. Three patients required additional treatment with amphotericin B and
      one required systemic MA. None of the patients developed mucosal lesions when
      followed up to 60 months. Intralesional MA is an effective and less toxic
      alternative treatment of patients with CL and contraindication to systemic
      therapy.

PMID- 22855755
TI  - Successful treatment of canine cutaneous leishmaniasis using radio-frequency
      induced heat (RFH) therapy.
AB  - Canine cutaneous leishmaniasis (CCL) is a significant veterinary problem.
      Infected dogs also serve as parasite reservoirs and contribute to human
      transmission of cutaneous leishmaniasis (CL). Current treatments for CCL are
      cumbersome and toxic because they are prolonged and involve multiple injections
      of antimonials. Radio-frequency induced heat (RFH) therapy has been found to be
      highly effective against CL in humans. Here, we examined the efficacy of topical
      RFH therapy in the treatment of CL in two pet dogs. We found that RFH therapy
      induced complete clinical cure and lesion healing within 45 days and both dogs
      have remained disease free for the last 16 months. This report is the first to
      demonstrate that a single topical application of RFH therapy is safe and
      effective in inducing long-term cure of CCL.

PMID- 22855756
TI  - Human African trypanosomiasis in a traveler: diagnostic pitfalls.
AB  - Abstract. An Israeli traveler returning from Tanzania presented with a relapsing
      febrile illness. A diagnosis of Trypanosoma brucei rhodesiense infection was
      established by blood smear after nearly a month. Blood polymerase chain reaction
      failed to provide an early diagnosis of human African trypanososmiasis.
      Recognition of suggestive signs should prompt physicians to perform repeated
      tests before ruling out human African trypanososmiasis.

PMID- 22855757
TI  - Evaluation of in-house ELISA using Trypanosoma cruzi lysate and recombinant
      antigens for diagnosis of Chagas disease and discrimination of its clinical
      forms.
AB  - The aim of this work was to investigate the potential usefulness of Trypanosoma
      cruzi lysate, recombinant protein JL7, and peptides P013, R13, JL18, JL19, and
      P0beta as serological markers for human Chagas disease. We analyzed 228 sera from
      Brazilian Chagas disease patients classified into four clinical groups and 108
      from non-chagasic patients. We defined the diagnostic sensitivity, specificity,
      and Kappa index measured by enzyme-linked immunosorbent assay (ELISA). As
      previously described, the highest values of diagnostic parameters were achieved
      for T. cruzi lysate and JL7; peptide P013 showed high specificity but low
      sensitivity. The other peptides resulted in lower sensitivity and specificity in
      our ELISA than T. cruzi lysate and JL7 protein. Antibodies against JL7 protein
      were mainly detected in sera from patients with severe chagasic cardiomyopathy,
      compared with those from the indeterminate form, whereas peptides failed to
      discriminate between the clinical forms of the disease.

PMID- 22855758
TI  - Evidence for stopping mass drug administration for lymphatic filariasis in some,
      but not all local government areas of Plateau and Nasarawa States, Nigeria.
AB  - An average of six annual rounds of ivermectin and albendazole were distributed in
      Plateau and Nasarawa States, Nigeria, to eliminate lymphatic filariasis. From
      2007 to 2008, population-based surveys were implemented in all 30 local
      government areas (LGAs) of the two states to determine the prevalence of
      Wuchereria bancrofti antigenemia to assess which LGA mass drug administration
      (MDA) could be halted. In total, 36,681 persons from 7,819 households were
      examined for filarial antigen as determined by immunochromatographic card tests.
      Overall antigen prevalence was 3.05% (exact upper 95% confidence interval [CI] =
      3.41%) with an upper 95% CI range by LGA of 0.50-19.3%. Among 3,233 children 6-7
      years of age, overall antigen prevalence was 1.71% (exact upper 95% CI = 2.19%),
      too high to recommend generally halting MDA in the two-state area. However, based
      on criteria of < 2% antigenemia among persons > 2 years of age, stopping MDA was
      recommended for 10 LGAs.

PMID- 22855759
TI  - A cross-sectional study of Taenia solium in a multiple taeniid-endemic region
      reveals competition may be protective.
AB  - We conducted cross-sectional surveys for taeniasis and cysticercosis in humans,
      pigs, and dogs in four northern provinces of Laos. Human cysticercosis and
      taeniasis prevalence was 2.2% (95% confidence interval [CI] = 1.4-3.0%) and 8.4%
      (95% CI = 6.9-9.9%), respectively. Eating uncooked beef, being male, province of
      residence, age, and ethnicity were significant risk factors for taeniasis and
      only province of residence was a significant risk factor for cystiercosis. Thirty
      five human tapeworms were recovered during the survey and 33 (94.3%) and 2 (5.7%)
      were identified as Taenia saginata and T. solium, respectively. Maximum
      likelihood adjusted prevalence of T. solium and T. hydatigena in pigs was 4.2%
      (95% CI = 0.5-7.9%) and 55.9% (95% CI = 47.5-64.3%), respectively, and T.
      hydatigena taeniasis in dogs was 4.8% (95% CI = 0.0-11.3%). Taenia hydatigena and
      T. saginata were the most prevalent taeniids in the respective pig and human
      populations and together may suppress T. solium transmission.

PMID- 22855760
TI  - Efficacy of diverse antiparasitic treatments for cysticercosis in the pig model.
AB  - Taenia solium cysticercosis infects pigs and humans. Because antiparasitic
      treatment for human cysticercosis has sub-optimal efficacy, alternative regimes
      are needed. Seven antiparasitic regimens were tested in 42 naturally infected
      pigs with cysticercosis, and compared with prednisone alone (n = 6) or no
      treatment (n = 6). The numbers of viable cysts in muscles and in the brain were
      examined after necropsy and were significantly decreased in pigs receiving
      combined albendazole plus praziquantel, albendazole alone, or oxfendazole. Pigs
      receiving praziquantel alone and nitazoxanide had numerous surviving cysts.
      Control (untreated) pigs and prednisone-treated pigs had many more viable cysts,
      suggesting no effect. Combined albendazole plus praziquantel, and oxfendazole,
      showed a strong cysticidal effect and provide suitable alternative treatments to
      be further explored for their use for treatment of human neurocysticercosis.

PMID- 22855761
TI  - Outbreak of human trichinellosis in Northern California caused by Trichinella
      murrelli.
AB  - In October of 2008, an outbreak of trichinellosis occurred in northern California
      that sickened 30 of 38 attendees of an event at which meat from a black bear was
      served. Morphologic and molecular testing of muscle from the leftover portion of
      bear meat revealed that the bear was infected with Trichinella murrelli, a
      sylvatic species of Trichinella found in temperate North America. Clinical
      records revealed a high attack rate for this outbreak: 78% for persons consuming
      any bear meat and 100% for persons consuming raw or undercooked bear meat. To our
      knowledge, this report is the first published report of a human trichinellosis
      outbreak in the United States attributed to T. murrelli, and it is the second
      such outbreak reported worldwide.

PMID- 22855762
TI  - Serum Aspergillus galactomannan for the management of disseminated histoplasmosis
      in AIDS.
AB  - Disseminated histoplasmosis is an emerging infection in patients with cellular
      immune deficiency in non-endemic countries, caused by the migration from endemic
      regions and the development of travels. Diagnosis can be challenging in this
      context because rapid diagnostic tools such as Histoplasma antigen detection or
      appropriate molecular tools are generally unavailable, serology is often negative
      in immunosuppressed patients, and isolation of the fungus from cultures often
      takes several weeks. Here, we report the contribution of galactomannan serum
      detection for the management of an HIV-infected patient with disseminated
      histoplasmosis.

PMID- 22855763
TI  - Prevalence of anemia and its risk factors among children 6-36 months old in
      Burma.
AB  - Anemia is a common nutritional problem, and it has a remarkably high prevalence
      rate in Southeast Asia. In this study, children from 6 to 36 months were
      investigated to determine (1) the prevalence of anemia and (2) risk factors
      associated with anemia. Convenience sampling was used to select three villages in
      three different regions in Burma. Hemoglobin and anthropometric indicators were
      measured for 872 children. Logistic regression analyses were used to determine
      factors associated with anemia. The overall prevalence of anemia was 72.6%, with
      40.0% having severe anemia. Predictors of anemia are a young age (P < 0.001),
      mother with anemia (P < 0.001), height-for-age Z score < -2 (P = 0.017), low
      family income (P < 0.001), mothers without primary education (P = 0.007),
      drinking unboiled water (P = 0.029), and fever in the last 3 months (P = 0.001).
      There is a high prevalence of anemia in children, and their nutritional status is
      quite poor. To control anemia, humanitarians and governments should launch
      comprehensive interventions.

PMID- 22855764
TI  - Hotel clinic-based diarrheal and respiratory disease surveillance in U.S. service
      members participating in Operation Bright Star in Egypt, 2009.
AB  - We conducted clinic-based, influenza-like illness and diarrheal disease
      surveillance among U.S. service members participating in Operation Bright Star
      2009. Epidemiologic data and samples were collected. Nasopharyngeal swab
      specimens were tested for viruses, and feces was tested for microbiologic,
      immunologic, and molecular diagnostics. A survey was used to collect self
      reported data. From 1,529 surveys, 41% reported diarrheal disease and 25%
      reported respiratory illness (incidence rate = 62 of 100 versus 37 of 100 person
      months; incidence rate ratio = 1.7, 95% confidence interval = 1.5-1.9).
      Enterotoxigenic Escherichia coli was identified in 74% (69 of 93) of fecal
      samples. In the influenza-like illness case series, 17% (9 of 52) were positive
      for influenza A; all were positive for pandemic (pH1N1) 2009 virus. Rates of
      decreased work performance reported by patients with diarrhea and influenza-like
      illness were similar (46% versus 48%; P = 0.8). Diarrheal diseases and
      respiratory illness remain common among deployed military personnel, with
      important operational impact. Despite an ongoing influenza pandemic, diarrheal
      disease incidence was higher than that of respiratory illness.

PMID- 22855767
TI  - Leptospira infection prevalence in small mammal host populations on three
      Hawaiian islands.
AB  - We describe the geographic distribution and variation in host-pathogen
      specificity for Leptospira-infected small mammals collected concurrently from
      three Hawaiian Islands over a period of 14 years: 1990-2003. Four serogroups
      (Icterohaemorrhagiae, Ballum, Sejroe, and Australis) were identified from the
      15,171 animals tested. Serogroup prevalence differed across host species and
      islands (P < 0.0001 for each), but not across years. The host associations and
      biogeographic patterns of Leptospira in Hawaii indicate a pathogen community
      shaped by ecological factors.

PMID- 22855766
TI  - Limited susceptibility of cynomolgus monkeys (Macaca fascicularis) to leprosy
      after experimental administration of Mycobacterium leprae.
AB  - Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility
      to M. leprae is unknown. A cynomolgus model of leprosy could increase
      understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions.
      We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three
      routes, with a median follow-up period of 6 years (range = 1-19 years) involving
      biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and
      lepromin skin testing. Most developed evanescent papules at intradermal M. leprae
      inoculation sites that, on biopsy, showed a robust cellular immune response akin
      to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy,
      four monkeys, without cutaneous or gross neurological signs of leprosy but with
      elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast
      bacilli (AFB), showed histological features, including AFB, suggestive of leprosy
      at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible
      to leprosy after experimental M. leprae administration.

PMID- 22855768
TI  - Scrub typhus among pediatric patients in Dambadeniya: a base hospital in Sri
      Lanka.
AB  - Data on pediatric scrub typhus is uncommon in Sri Lanka and other countries. The
      objective of this study was to identify the clinical features of patients with
      scrub typhus at a Base Hospital in Sri Lanka. Sixty patients presenting with
      suspected scrub typhus were included in the study. Their blood samples were
      tested for the presence of antibodies against rickettsioses using the reference
      method. Twenty patients had confirmed scrub typhus and 24 had possible scrub
      typhus. Their clinical features are discussed in this work.

PMID- 22855765
TI  - Identification of diverse Bartonella genotypes among small mammals from
      Democratic Republic of Congo and Tanzania.
AB  - Small mammals from the Democratic Republic (DR) of the Congo and Tanzania were
      tested to determine the prevalence and genetic diversity of Bartonella species.
      The presence of Bartonella DNA was assessed in spleen samples of the animals by
      rpoB- and gltA-polymerase chain reactions (PCRs). By rpoB-PCR, Bartonella was
      detected in 8 of 59 animals of DR Congo and in 16 of 39 Tanzanian animals. By
      gltA-PCR, Bartonella was detected in 5 and 15 animals of DR Congo and Tanzania,
      respectively. The gene sequences from Arvicanthis neumanni were closely related
      to Bartonella elizabethae. The genotypes from Lophuromys spp. and from Praomys
      delectorum were close to Bartonella tribocorum. Five genogroups were not
      genetically related to any known Bartonella species. These results suggest the
      need to conduct further studies to establish the zoonotic risks linked with those
      Bartonella species and, in particular, to verify whether these agents might be
      responsible for human cases of febrile illness of unknown etiology in Africa.

PMID- 22855769
TI  - A fatal urban case of rocky mountain spotted fever presenting an eschar in San
      Jose, Costa Rica.
AB  - This study reports the first urban human case of Rocky Mountain spotted fever
      caused by Rickettsia rickettsii, in Costa Rica. An 8-year-old female who died at
      the National Children's Hospital 4 days after her admission, and an important and
      significant observation was the presence of an "eschar" (tache noire), which is
      typical in some rickettsial infections but not frequent in Rocky Mountain spotted
      fever cases.

PMID- 22855771
TI  - Evaluation of a rapid analyte measurement platform for West Nile virus detection
      based on United States mosquito control programs.
AB  - The rapid analyte measurement platform (RAMP) system is an immunoassay test for
      West Nile virus (WNV) detection. Although reverse transcriptase-polymerase chain
      reaction (RT-PCR) methodology has been regarded as the gold standard for
      confirming WNV presence, usage of RAMP testing kits has increased in the past
      years. We collected RAMP test result data that were subsequently confirmed with
      RT-PCR methodology from mosquito control agencies to evaluate the efficacy of the
      RAMP testing. Results indicate that there are a high number of false positives
      (RAMP positive, RT-PCR negative) with RAMP testing. Correlation between RAMP unit
      values and RT-PCR cycle threshold values were varied depending on the
      primer/probe being compared. Comparison of RT-PCR results (on the same samples)
      between laboratories also indicates variation among the procedures and their
      potential to influence the RAMP testing efficacies. We discuss the potential
      issues and solutions that could prevent the high rate of false positives.

PMID- 22855772
TI  - Application of an autoregressive integrated moving average model for predicting
      the incidence of hemorrhagic fever with renal syndrome.
AB  - The Box-Jenkins approach was used to fit an autoregressive integrated moving
      average (ARIMA) model to the incidence of hemorrhagic fever with renal Syndrome
      (HFRS) in China during 1986-2009. The ARIMA (0, 1, 1) * (2, 1, 0)(12) models
      fitted exactly with the number of cases during January 1986-December 2009. The
      fitted model was then used to predict HFRS incidence during 2010, and the number
      of cases during January-December 2010 fell within the model's confidence interval
      for the predicted number of cases in 2010. This finding suggests that the ARIMA
      model fits the fluctuations in HFRS frequency and it can be used for future
      forecasting when applied to HFRS prevention and control.

PMID- 22855770
TI  - Molecular characterization and phylogenetic analysis of dengue viruses imported
      into Taiwan during 2008-2010.
AB  - We present our surveillance results on imported dengue cases in Taiwan during
      2008-2010. A total of 734 imported dengue patients were identified. The travelers
      were arriving from 18 countries, including Southeast Asia, the Indian
      subcontinent, South Pacific islands, and Latin America. Gene sequences from 358
      dengue virus (DENV) isolates were used to perform phylogenetic analyses, thus,
      providing an updated view of the geographic distribution and dynamic transmission
      of DENV strains circulating in these countries. Our results suggest that the DENV
      1 genotype I and DENV-2 Cosmopolitan genotype comprise the predominant DENV
      strains circulating in Southeast Asian countries. The DENV-3 Genotype III strain
      was found to be newly emerging in several Southeast Asian countries, however, the
      Asian genotype 2 and the Asian/American genotype of DENV-2 strains appeared to be
      less prevalent in Southeast Asia. Furthermore, imported dengue viruses are
      representative of the overall patterns of serotype/genotype frequencies of dengue
      outbreaks that occurred in Taiwan.

PMID- 22855773
TI  - Hantavirus infection prevalence in wild rodents and human anti-hantavirus
      serological profiles from different geographic areas of South Brazil.
AB  - Parana state presents the fourth highest number of accumulated cases of
      hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus
      transmission we carried out a study based on rodent trapping and determined the
      anti-hantavirus seroprevalence in these animals and in the inhabitants of these
      localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%,
      respectively. Eighty-two percent of the seropositive rodents were genetically
      analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples
      cluster with Araucaria (Juquitiba-like) or Jabora hantavirus genotypes. The
      Jabora strain was identified in Akodon serrensis and Akodon montensis, whereas
      the Araucaria strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A.
      montensis, and Akodon paranaensis, with the latter species being identified for
      the first time as a natural host. These findings expose the complex relationships
      between virus and reservoirs in Brazil, which could have an impact on hantavirus
      transmission dynamics in nature and human epidemiology.

PMID- 22855775
TI  - 5-hydroxytryptamine 2C receptors tonically augment synaptic currents in the
      nucleus tractus solitarii.
AB  - The nucleus tractus solitarii (nTS) is the primary termination and integration
      point for visceral afferents in the brain stem. Afferent glutamate release and
      its efficacy on postsynaptic activity within this nucleus are modulated by
      additional neuromodulators and transmitters, including serotonin (5-HT) acting
      through its receptors. The 5-HT(2) receptors in the medulla modulate the
      cardiorespiratory system and autonomic reflexes, but the distribution of the 5
      HT(2C) receptor and the role of these receptors during synaptic transmission in
      the nTS remain largely unknown. In the present study, we examined the
      distribution of 5-HT(2C) receptors in the nTS and their role in modulating
      excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons in the
      horizontal brain stem slice. Real-time RT-PCR and immunohistochemistry identified
      5-HT(2C) receptor message and protein in the nTS and suggested postsynaptic
      localization. In nTS neurons innervated by general visceral afferents, 5-HT(2C)
      receptor activation increased solitary tract (TS)-EPSC amplitude and input
      resistance and depolarized membrane potential. Conversely, 5-HT(2C) receptor
      blockade reduced TS-EPSC and miniature EPSC amplitude, as well as input
      resistance, and hyperpolarized membrane potential. Synaptic parameters in nTS
      neurons that receive sensory input from carotid body chemoafferents were also
      attenuated by 5-HT(2C) receptor blockade. Taken together, these data suggest that
      5-HT(2C) receptors in the nTS are located postsynaptically and augment excitatory
      neurotransmission.

PMID- 22855777
TI  - Transcranial electrical stimulation over visual cortex evokes phosphenes with a
      retinal origin.
AB  - Transcranial electrical stimulation (tES) is a promising therapeutic tool for a
      range of neurological diseases. Understanding how the small currents used in tES
      spread across the scalp and penetrate the brain will be important for the
      rational design of tES therapies. Alternating currents applied transcranially
      above visual cortex induce the perception of flashes of light (phosphenes). This
      makes the visual system a useful model to study tES. One hypothesis is that tES
      generates phosphenes by direct stimulation of the cortex underneath the
      transcranial electrode. Here, we provide evidence for the alternative hypothesis
      that phosphenes are generated in the retina by current spread from the occipital
      electrode. Building on the existing literature, we first confirm that phosphenes
      are induced at lower currents when electrodes are placed farther away from visual
      cortex and closer to the eye. Second, we explain the temporal frequency tuning of
      phosphenes based on the well-known response properties of primate retinal
      ganglion cells. Third, we show that there is no difference in the time it takes
      to evoke phosphenes in the retina or by stimulation above visual cortex.
      Together, these findings suggest that phosphenes induced by tES over visual
      cortex originate in the retina. From this, we infer that tES currents spread well
      beyond the area of stimulation and are unlikely to lead to focal neural
      activation. Novel stimulation protocols that optimize current distributions are
      needed to overcome these limitations of tES.

PMID- 22855776
TI  - Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle
      afferent neurons.
AB  - Muscle afferents are critical regulators of motor function (Group I and II) and
      cardiovascular responses to exercise (Group III and IV). However, little is known
      regarding the expressed voltage-dependent ion channels. We identified muscle
      afferent neurons in dorsal root ganglia (DRGs), using retrograde labeling to
      examine voltage-dependent sodium (Na(V)) channels. In patch-clamp recordings, we
      found that the dominant Na(V) current in the majority of identified neurons was
      insensitive to tetrodotoxin (TTX-R), with Na(V) current in only a few (14%)
      neurons showing substantial (>50%) TTX sensitivity (TTX-S). The TTX-R current was
      sensitive to a Na(V)1.8 channel blocker, A803467. Immunocytochemistry
      demonstrated labeling of muscle afferent neurons by a Na(V)1.8 antibody, which
      further supported expression of these channels. A portion of the TTX-R Na(V)
      current appeared to be noninactivating during our 25-ms voltage steps, which
      suggested activity of Na(V)1.9 channels. The majority of the noninactivating
      current was insensitive to A803467 but sensitive to extracellular sodium.
      Immunocytochemistry showed labeling of muscle afferent neurons by a Na(V)1.9
      channel antibody, which supports expression of these channels. Further
      examination of the muscle afferent neurons showed that functional TTX-S channels
      were expressed, but were largely inactivated at physiological membrane
      potentials. Immunocytochemistry showed expression of the TTX-S channels Na(V)1.6
      and Na(V)1.7 but not Na(V)1.1. Na(V)1.8 and Na(V)1.9 appear to be the dominant
      functional sodium channels in small- to medium-diameter muscle afferent neurons.
      The expression of these channels is consistent with the identification of these
      neurons as Group III and IV, which mediate the exercise pressor reflex.

PMID- 22855778
TI  - Reframing the action and perception dissociation in DF: haptics matters, but how?
AB  - Goodale and Milner's (1992) "vision-for-action" and "vision-for-perception"
      account of the division of labor between the dorsal and ventral "streams" has
      come to dominate contemporary views of the functional roles of these two
      pathways. Nevertheless, some lines of evidence for the model remain
      controversial. Recently, Thomas Schenk reexamined visual form agnosic patient
      DF's spared anticipatory grip scaling to object size, one of the principal
      empirical pillars of the model. Based on this new evidence, Schenk rejects the
      original interpretation of DF's spared ability that was based on segregated
      processing of object size and argues that DF's spared grip scaling relies on
      haptic feedback to calibrate visual egocentric cues that relate the posture of
      the hand to the visible edges of the goal-object. However, a careful
      consideration of the tasks that Schenk employed reveals some problems with his
      claim. We suspect that the core issues of this controversy will require a closer
      examination of the role that cognition plays in the operation of the dorsal and
      ventral streams in healthy controls and in patient DF.

PMID- 22855779
TI  - The effect of high-frequency conditioning stimulation of human skin on reported
      pain intensity and event-related potentials.
AB  - High-frequency conditioning electrical stimulation (HFS) of human skin induces an
      increased pain sensitivity to mechanical stimuli in the surrounding
      nonconditioned skin. The aim of this study was to investigate the effect of HFS
      on reported pain sensitivity to single electrical stimuli applied within the area
      of conditioning stimulation. We also investigated the central nervous system
      responsiveness to these electrical stimuli by measuring event-related potentials
      (ERPs). Single electrical test stimuli were applied in the conditioned area
      before and 30 min after HFS. During electrical test stimulation, the reported
      pain intensity (numerical rating scale) and EEG (ERPs) were measured. Thirty
      minutes after conditioning stimulation, we observed a decrease of reported pain
      intensity at both the conditioned and control (opposite arm) skin site in
      response to the single electrical test stimuli. In contrast, we observed enhanced
      ERP amplitudes after HFS at the conditioned skin site, compared with control
      site, in response to the single electrical test stimuli. Recently, it has been
      proposed that ERPs, at least partly, reflect a saliency detection system.
      Therefore, the enhanced ERPs might reflect enhanced saliency to potentially
      threatening stimuli.

PMID- 22855781
TI  - Investigating the impact of hepatitis B virus surface gene polymorphism on
      antigenicity using ex vivo phenotyping.
AB  - The hepatitis B virus (HBV) surface antigen (HBsAg) is a complex protein, and
      understanding accurately the impact of amino acid changes on the antigenicity of
      the immunodominant a determinant must take this complexity into consideration.
      Epitope mapping with four mAbs was used to phenotype HBsAg directly from
      patients' sera to investigate the effect of mutations in their native genetic
      backbone. The expected mAb reactivity was established initially for samples
      harbouring 'wild-type' HBsAg sequences across genotypes A-E. The alteration of
      HBsAg antigenicity, defined by mAb epitope loss, was demonstrated in a number of
      samples with sequence-inferred amino acid changes. Individual mutations within
      the mapped epitopes to which the mAbs were directed usually affected their
      binding. However, the loss of more than one epitope was observed as the number of
      mutations within a sequence increased. Conversely, not all mutations occurring in
      the a determinant altered the HBsAg conformation. The genotype backbone, the
      specific amino acid substitution and amino acid changes occurring outside the
      major antigenic region appeared to be important in determining expression of the
      predicted epitope loss. These data clearly demonstrate that sequence-based
      methods alone may not accurately define HBsAg phenotype. This phenotyping
      methodology allows for the rapid and accurate identification of antigenically
      altered viruses and will greatly enhance current HBV surveillance, research and
      diagnostic activities. The data generated can be used to inform on public health
      issues relating to prevalence, transmission and impact of HBsAg mutants in HBV
      infected populations.

PMID- 22855780
TI  - Association between prediagnostic IgE levels and risk of glioma.
AB  - BACKGROUND: Previous nested case-control studies suggest that a prediagnostic
      biomarker of allergy, IgE, is inversely associated with the risk of glioma, but
      these findings are inconsistent. The purpose of our study was to assess this
      association and determine how long before glioma diagnosis it may be observed.
      METHODS: We conducted a nested case-control study using serum specimens from the
      Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed
      with glioma (n = 594 case subjects), between January 1, 1974 to December 31,
      2007, were matched with subjects without glioma (n = 1177 control subjects) for
      date of blood collection, 2-year age interval at blood collection, and sex.
      Respiratory allergen-specific and total IgE levels in the serum were measured
      using fluorescent assays. Odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated using conditional logistic regression models stratified on sex
      and glioblastoma, the most common glioma subtype. Data were stratified on time
      from blood collection to tumor diagnosis to assess how long before glioma
      diagnosis the association could be observed. RESULTS: Among women, testing
      positive for allergen-specific IgE (>0.35 kU(A)/L) was associated with decreased
      risk of glioblastoma compared with testing negative (<=0.35 kU(A)/L; OR = 0.46,
      95% CI = 0.23 to 0.93). Among both sexes combined, testing positive for total IgE
      (>100 kU/L) was associated with decreased risk of glioma compared with testing
      negative (<=100 kU/L; OR = 0.75, 95% CI = 0.56 to 0.99), and simultaneously
      testing positive for allergen-specific IgE and total IgE was associated with a
      borderline statistically significantly decreased risk of glioblastoma and glioma
      compared with simultaneously testing negative for these types of IgE. Testing
      positive for total IgE at least 20 years before diagnosis was associated with
      decreased risk of glioma compared with testing negative (OR = 0.54, 95% CI = 0.30
      to 0.99). CONCLUSION: An inverse association between IgE levels and risk of
      glioma was detected; the association was present at least 20 years before tumor
      diagnosis.

PMID- 22855782
TI  - Evidence of multiple introductions of beak and feather disease virus into the
      Pacific islands of Nouvelle-Caledonie (New Caledonia).
AB  - Beak and feather disease virus (BFDV) is a circular ssDNA virus that causes
      psittacine beak and feather disease and has almost global presence. Here, we
      report for the first time the presence of in Nouvelle-Caledonie (New Caledonia).
      One hundred and sixty-eight exotic and 79 endemic birds were sampled in Nouvelle
      Caledonie, 26 were found to be positive for BFDV. We characterized the full
      genomes of 26 isolates and phylogenetic analysis placed nine of the isolates into
      the BFDV-J strain, with the remaining 17 isolates from Deplanche's Rainbow
      Lorikeet (Trichoglossus haematodus deplanchii) forming a novel strain, BFDV-P. Of
      more concern was the discovery of an infected bird from the vulnerable and
      endemic New Caledonian Parakeet (Cyanoramphus saisseti). Our results reveal that
      there have been at least two introductions of BFDV into Nouvelle-Caledonie.

PMID- 22855783
TI  - A baculovirus isolated from wild silkworm encompasses the host ranges of Bombyx
      mori nucleopolyhedrosis virus and Autographa californica multiple
      nucleopolyhedrovirus in cultured cells.
AB  - A baculovirus, named BomaNPV S2, was isolated from a diseased larva of the wild
      silkworm, Bombyx mandarina. Notably, BomaNPV S2 exhibited a distinguishing
      feature in that its host range covered that of both Bombyx mori
      nucleopolyhedrosis virus (BmNPV) and Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) in cultured cells. It could replicate in cells of
      B. mori (Bm5 and BmN), Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn-5B1
      4). However, occlusion-derived virions of BomaNPV S2 in B. mori cells contained
      only a single nucleocapsid, whereas they contained multiple nucleocapsids in Tn
      5B1-4 cells. The complete genome sequence of BomaNPV S2, including predicted
      ORFs, was determined and compared with the genome sequence of its close
      relatives. The comparison results showed that most of the BomaNPV S2 genome
      sequence was shared with BmNPV (BmNPV T3) or BomaNPV S1, but several regions
      seemed more similar to regions of AcMNPV. This observation might explain why
      BomaNPV S2 covers the host ranges of BmNPV and AcMNPV. Further recombinant virus
      infection experiments demonstrated that GP64 plays an important role in BomaNPV
      S2 host-range determination.

PMID- 22855784
TI  - Recombinant expression of the coat protein of Botrytis virus X and development of
      an immunofluorescence detection method to study its intracellular distribution in
      Botrytis cinerea.
AB  - Botrytis cinerea is infected by many mycoviruses with varying phenotypical
      effects on the fungal host, including Botrytis virus X (BVX), a mycovirus that
      has been found in several B. cinerea isolates worldwide with no obvious effects
      on growth. Here we present results from serological and immunofluorescence
      microscopy (IFM) studies using antiserum raised against the coat protein of BVX
      expressed in Escherichia coli fused to maltose-binding protein. Due to the high
      yield of recombinant protein it was possible to raise antibodies that recognized
      BVX particles. An indirect ELISA, using BVX antibodies, detected BVX in partially
      purified virus preparations from fungal isolates containing BVX alone and in
      mixed infection with Botrytis virus F. The BVX antiserum also proved suitable for
      IFM studies. Intensely fluorescing spots (presumed to be virus aggregates) were
      found to be localized in hyphal cell compartments and spores of natural and
      experimentally infected B. cinerea isolates using IFM. Immunofluorescently
      labelled sections through fungal tissue, as well as fixed mycelia grown on glass
      slides, showed aggregations of virions closely associated with fungal cell
      membranes and walls, next to septal pores, and in hyphal tips. Also, calcofluor
      white staining of mature cell walls of virus-transfected Botrytis clones revealed
      numerous cell wall areas with increased amounts of chitin/glycoproteins. Our
      results indicate that some BVX aggregates are closely associated with the fungal
      cell wall and raise the question of whether mycoviruses may be able to move
      through the wall and therefore not be totally dependent on intracellular routes
      of transmission.

PMID- 22855785
TI  - Photodynamic inactivation of prions by disulfonated hydroxyaluminium
      phthalocyanine.
AB  - Sulfonated phthalocyanines (Pcs) are cyclic tetrapyrroles that constitute a group
      of photosensitizers. In the presence of visible light and diatomic oxygen, Pcs
      produce singlet oxygen and other reactive oxygen species that have known
      degradation effects on lipids, proteins and/or nucleic acids. Pcs have been used
      successfully in the treatment of bacterial, yeast and fungal infections, but
      their use in the photodynamic inactivation of prions has never been reported.
      Here, we evaluated the photodynamic activity of the disodium salt of disulfonated
      hydroxyaluminium phthalocyanine (PcDS) against mouse-adapted scrapie RML prions
      in vitro. PcDS treatment of RML brain homogenate resulted in a time- and dose
      dependent inactivation of prions. The photodynamic potential of Pcs offers a new
      way to inactivate prions using biodegradable compounds at room temperature and
      normal pressure, which could be useful for treating thermolabile materials and
      liquids.

PMID- 22855786
TI  - DNA viruses and the cellular DNA-damage response.
AB  - It is clear that a number of host-cell factors facilitate virus replication and,
      conversely, a number of other factors possess inherent antiviral activity.
      Research, particularly over the last decade or so, has revealed that there is a
      complex inter-relationship between viral infection and the host-cell DNA-damage
      response and repair pathways. There is now a realization that viruses can
      selectively activate and/or repress specific components of these host-cell
      pathways in a temporally coordinated manner, in order to promote virus
      replication. Thus, some viruses, such as simian virus 40, require active DNA
      repair pathways for optimal virus replication, whereas others, such as
      adenovirus, go to considerable lengths to inactivate some pathways. Although
      there is ever-increasing molecular insight into how viruses interact with host
      cell damage pathways, the precise molecular roles of these pathways in virus life
      cycles is not well understood. The object of this review is to consider how DNA
      viruses have evolved to manage the function of three principal DNA damage
      response pathways controlled by the three phosphoinositide 3-kinase (PI3K)
      related protein kinases ATM, ATR and DNA-PK and to explore further how virus
      interactions with these pathways promote virus replication.

PMID- 22855787
TI  - Patient-derived hepatitis C virus and JFH-1 clones differ in their ability to
      infect human hepatoma cells and lymphocytes.
AB  - Hepatitis C virus (HCV) is a hepatotropic virus that also infects cells of the
      immune system. HCV clones cultivated in human hepatoma Huh-7.5 cells have
      significantly advanced our understanding of HCV replication and candidate
      hepatocyte receptors. However, naturally occurring patient-derived HCV, in
      contrast to the HCV JFH-1 clone, is unable to infect Huh-7.5 cells, while it can
      replicate in human primary T-cells and selected T-cell lines. To better
      understand this incongruity, we examined the susceptibility of primary T-cells,
      PBMCs and T-cell lines to infection with patient-derived HCV, the classical HCV
      JFH-1 and a cell culture-adapted JFH1(T) known to be highly infectious to Huh-7.5
      cells. We also tested whether Huh-7.5 cells are prone to virus readily infecting
      T-lymphocytes. The results revealed that while primary T-cells and Molt4 and
      Jurkat T-cell lines were susceptible to patient-derived HCV, they were resistant
      to infection with either JFH1(T) or JFH-1. However, the JFH1(T) clone interacted
      more firmly, although non-productively, with the cells than JFH-1. Further, Huh
      7.5 cells robustly supported replication of JFH1(T) but not patient-derived, wild
      type virus, despite using highly sensitive detection assays. In conclusion, JFH-1
      and JFH1(T) clones were unable to establish productive infection in human primary
      T-cells, PBMCs and T-cell lines known to be prone to infection by patient-derived
      HCV, while Huh-7.5 cells were resistant to infection with naturally occurring
      virus infecting immune cells. The data showed that the ability to infect
      lymphocytes is a characteristic of native virus but not laboratory HCV clones.

PMID- 22855788
TI  - Effect of resistance training during Ramadan on body composition and markers of
      renal function, metabolism, inflammation, and immunity in recreational
      bodybuilders.
AB  - The aim of this study was to evaluate the effects of a hypertrophic training
      program during Ramadan on body composition and selected metabolic markers in
      trained bodybuilders. Sixteen male recreational bodybuilders (9 Ramadan fasters
      and 7 nonfasters) participated in the study. All visited the laboratory 2 d
      before the start of Ramadan (Bef-R) and on the 29th day of Ramadan (End-R). In
      the morning of each session, subjects underwent anthropometric measurement,
      completed a dietary questionnaire, and provided fasting blood and urine samples.
      Body mass and body-mass index in nonfasters increased by 2.4% (p = .05 and p =
      .04, respectively) from Bef-R to End-R but remained unchanged in fasters over the
      period of the investigation. Fasters experienced an increase in the following
      parameters from Bef-R to End-R: urine specific gravity (1%, p = .022) and serum
      concentrations of urea (5%, p = .008), creatinine (5%, p = .007), uric acid (17%,
      p < .001), sodium (2%, p = .019), potassium (6%, p = .006), chloride (2%, p =
      .028), and high-density lipoprotein cholesterol (10%, p = .005). However, only
      serum creatinine and low-density lipoprotein cholesterol increased in nonfasters
      (3%, p <.001 and 14%, p = .007, respectively) during the same period. Creatinine
      clearance values of fasters decreased by 3% (p = .03) from Bef-R to End-R.
      Continuance of hypertrophic training through Ramadan had no effect on body mass
      and body composition of bodybuilders, but a state of dehydration and reduced
      renal function were apparent, perhaps because of the restricted opportunity for
      fluid intake imposed by the study design.

PMID- 22855789
TI  - Spatial and functional relationships among Pol V-associated loci, Pol IV
      dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome.
AB  - Multisubunit RNA polymerases IV and V (Pols IV and V) mediate RNA-directed DNA
      methylation and transcriptional silencing of retrotransposons and heterochromatic
      repeats in plants. We identified genomic sites of Pol V occupancy in parallel
      with siRNA deep sequencing and methylcytosine mapping, comparing wild-type plants
      with mutants defective for Pol IV, Pol V, or both Pols IV and V. Approximately
      60% of Pol V-associated regions encompass regions of 24-nucleotide (nt) siRNA
      complementarity and cytosine methylation, consistent with cytosine methylation
      being guided by base-pairing of Pol IV-dependent siRNAs with Pol V transcripts.
      However, 27% of Pol V peaks do not overlap sites of 24-nt siRNA biogenesis or
      cytosine methylation, indicating that Pol V alone does not specify sites of
      cytosine methylation. Surprisingly, the number of methylated CHH motifs, a
      hallmark of RNA-directed de novo methylation, is similar in wild-type plants and
      Pol IV or Pol V mutants. In the mutants, methylation is lost at 50%-60% of the
      CHH sites that are methylated in the wild type but is gained at new CHH
      positions, primarily in pericentromeric regions. These results indicate that Pol
      IV and Pol V are not required for cytosine methyltransferase activity but shape
      the epigenome by guiding CHH methylation to specific genomic sites.

PMID- 22855790
TI  - Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in
      medulloblastoma via regulating cell volume dynamics.
AB  - Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify
      EAG2 as an overexpressed potassium channel in MBs across different molecular and
      histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro,
      but also reduces tumor burden in vivo and enhances survival in xenograft studies.
      Mechanistically, we demonstrate that EAG2 protein is confined intracellularly
      during interphase but is enriched in the plasma membrane during late G2 phase and
      mitosis. Disruption of EAG2 expression results in G2 arrest and mitotic
      catastrophe associated with failure of premitotic cytoplasmic condensation. While
      the tumor suppression function of EAG2 knockdown is independent of p53
      activation, DNA damage checkpoint activation, or changes in the AKT pathway, this
      defective cell volume control is specifically associated with hyperactivation of
      the p38 MAPK pathway. Inhibition of the p38 pathway significantly rescues the
      growth defect and G2 arrest. Strikingly, ectopic membrane expression of EAG2 in
      cells at interphase results in cell volume reduction and mitotic-like morphology.
      Our study establishes the functional significance of EAG2 in promoting MB tumor
      progression via regulating cell volume dynamics, the perturbation of which
      activates the tumor suppressor p38 MAPK pathway, and provides clinical relevance
      for targeting this ion channel in human MBs.

PMID- 22855791
TI  - Identification of a DNA methylation-independent imprinting control region at the
      Arabidopsis MEDEA locus.
AB  - Genomic imprinting is exclusive to mammals and seed plants and refers to parent
      of-origin-dependent, differential transcription. As previously shown in mammals,
      studies in Arabidopsis have implicated DNA methylation as an important hallmark
      of imprinting. The current model suggests that maternally expressed imprinted
      genes, such as MEDEA (MEA), are activated by the DNA glycosylase DEMETER (DME),
      which removes DNA methylation established by the DNA methyltransferase MET1. We
      report the systematic functional dissection of the MEA cis-regulatory region,
      resulting in the identification of a 200-bp fragment that is necessary and
      sufficient to mediate MEA activation and imprinted expression, thus containing
      the imprinting control region (ICR). Notably, imprinted MEA expression mediated
      by this ICR is independent of DME and MET1, consistent with the lack of any
      significant DNA methylation in this region. This is the first example of an ICR
      without differential DNA methylation, suggesting that factors other than DME and
      MET1 are required for imprinting at the MEA locus.

PMID- 22855793
TI  - Neurally constrained cognitive modeling clarifies how action plans are changed.

PMID- 22855792
TI  - Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause
      centrosome reduplication.
AB  - Like DNA replication, centrosomes are licensed to duplicate once per cell
      division cycle to ensure genetic stability. In addition to regulating DNA
      replication, the Orc1 subunit of the human origin recognition complex controls
      centriole and centrosome copy number. Here we report that Orc1 harbors a PACT
      centrosome-targeting domain and a separate domain that differentially inhibits
      the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin
      binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin
      A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In
      contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different
      mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome
      patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the
      PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier
      Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow
      centrosome reduplication. Thus, Orc1 contains distinct domains that control
      centrosome copy number and DNA replication. We suggest that the Orc1 mutations
      present in some Meier-Gorlin syndrome patients contribute to the pronounced
      microcephaly and dwarfism observed in these individuals by altering centrosome
      duplication in addition to DNA replication defects.

PMID- 22855794
TI  - Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed
      rewards.
AB  - The forebrain serotonergic system is a crucial component in the control of
      impulsive behaviors. We previously reported that the activity of serotonin
      neurons in the midbrain dorsal raphe nucleus increased when rats performed a task
      that required them to wait for delayed rewards. However, the causal relationship
      between serotonin neural activity and the tolerance for the delayed reward
      remained unclear. Here, we test whether the inhibition of serotonin neural
      activity by the local application of the 5-HT(1A) receptor agonist 8-hydroxy-2
      (di-n-propylamino) tetralin in the dorsal raphe nucleus impairs rats' tolerance
      for delayed rewards. Rats performed a sequential food-water navigation task that
      required them to visit food and water sites alternately via a tone site to get
      rewards at both sites after delays. During the short (2 s) delayed reward
      condition, the inhibition of serotonin neural activity did not significantly
      influence the numbers of reward choice errors (nosepoke at an incorrect reward
      site following a conditioned reinforcer tone), reward wait errors (failure to
      wait for the delayed rewards), or total trials (sum of reward choice errors,
      reward wait errors, and acquired rewards). By contrast, during the long (7-11 s)
      delayed reward condition, the number of wait errors significantly increased while
      the numbers of total trials and choice errors did not significantly change. These
      results indicate that the activation of dorsal raphe serotonin neurons is
      necessary for waiting for long delayed rewards and suggest that elevated
      serotonin activity facilitates waiting behavior when there is the prospect of
      forthcoming rewards.

PMID- 22855795
TI  - A widely distributed spectral signature of task-negative electrocorticography
      responses revealed during a visuomotor task in the human cortex.
AB  - While research of human cortical function has typically focused on task-related
      increases in neuronal activity, there is a growing interest in the complementary
      phenomenon-namely, task-induced reductions. Recent human BOLD fMRI studies have
      associated such reductions with a specific network termed the default mode
      network (DMN). However, detailed understanding of the spatiotemporal patterns of
      task-negative responses and particularly how they compare across different
      cortical networks is lacking. Here we examined this issue in a large-scale
      electrocorticography study in patients performing a demanding backward masking
      task. Our results uncovered rapid (<1 s) task-induced reductions in gamma power,
      often concomitant with power increase in alpha/beta bands. Importantly, these
      responses were found both in the DMN and sensory-motor networks. Comparing the
      task-negative responses across these different networks revealed similar spectral
      signatures and dynamics. We hypothesize that the task-negative responses may
      reflect a cortical switching mechanism whose role is to steer activity away from
      cortical networks, which are inappropriate for the task at hand.

PMID- 22855796
TI  - Population-wide bias of surround suppression in auditory spatial receptive fields
      of the owl's midbrain.
AB  - The physical arrangement of receptive fields (RFs) within neural structures is
      important for local computations. Nonuniform distribution of tuning within
      populations of neurons can influence emergent tuning properties, causing bias in
      local processing. This issue was studied in the auditory system of barn owls. The
      owl's external nucleus of the inferior colliculus (ICx) contains a map of
      auditory space in which the frontal region is overrepresented. We measured
      spatiotemporal RFs of ICx neurons using spatial white noise. We found a
      population-wide bias in surround suppression such that suppression from frontal
      space was stronger. This asymmetry increased with laterality in spatial tuning.
      The bias could be explained by a model of lateral inhibition based on the
      overrepresentation of frontal space observed in ICx. The model predicted trends
      in surround suppression across ICx that matched the data. Thus, the uneven
      distribution of spatial tuning within the map could explain the topography of
      time-dependent tuning properties. This mechanism may have significant
      implications for the analysis of natural scenes by sensory systems.

PMID- 22855797
TI  - The resting transducer current drives spontaneous activity in prehearing
      mammalian cochlear inner hair cells.
AB  - Spontaneous Ca(2+)-dependent electrical activity in the immature mammalian
      cochlea is thought to instruct the formation of the tonotopic map during the
      differentiation of sensory hair cells and the auditory pathway. This activity
      occurs in inner hair cells (IHCs) during the first postnatal week, and the
      pattern differs along the cochlea. During the second postnatal week, which is
      before the onset of hearing in most rodents, the resting membrane potential for
      IHCs is apparently more hyperpolarized (approximately -75 mV), and it remains
      unclear whether spontaneous action potentials continue to occur. We found that
      when mouse IHC hair bundles were exposed to the estimated in vivo endolymphatic
      Ca(2+) concentration (0.3 mm) present in the immature cochlea, the increased open
      probability of the mechanotransducer channels caused the cells to depolarize to
      around the action potential threshold (approximately -55 mV). We propose that, in
      vivo, spontaneous Ca(2+) action potentials are intrinsically generated by IHCs up
      to the onset of hearing and that they are likely to influence the final sensory
      independent refinement of the developing cochlea.

PMID- 22855798
TI  - Nicotine exposure during adolescence leads to short- and long-term changes in
      spike timing-dependent plasticity in rat prefrontal cortex.
AB  - Adolescence is a critical period of brain development during which maturation of
      areas involved in cognitive functioning, such as the medial prefrontal cortex
      (mPFC), is still ongoing. Tobacco smoking during this age can compromise the
      normal course of prefrontal development and lead to cognitive impairments in
      later life. Recently, we reported that nicotine exposure during adolescence
      results in a short-term increase and lasting reduction in synaptic mGluR2 levels
      in the rat mPFC, causing attention deficits during adulthood. It is unknown how
      changed synaptic mGluR2 levels after adolescent nicotine exposure affect the
      ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we
      addressed this question. To model nicotine exposure, adolescent (P34-P43) or
      adult (P60-P69) rats were treated with nicotine injections three times per day
      for 10 d. We found that, both during acute activation of nicotinic receptors in
      the adolescent mPFC as well as immediately following nicotine treatment during
      adolescence, long-term plasticity in response to timed presynaptic and
      postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of
      adult rats 5 weeks after they received nicotine treatment during adolescence, but
      not during adulthood, tLTP was increased. Short- and long-term adaptation of mPFC
      synaptic plasticity after adolescent nicotine exposure could be explained by
      changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating
      mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure
      to nicotine during adolescence alters the rules for spike timing-dependent
      plasticity in prefrontal networks that may explain the observed deficits in
      cognitive performance in later life.

PMID- 22855799
TI  - Taste coding in the nucleus of the solitary tract of the awake, freely licking
      rat.
AB  - It is becoming increasingly clear that the brain processes sensory stimuli
      differently according to whether they are passively or actively acquired, and
      these differences can be seen early in the sensory pathway. In the nucleus of the
      solitary tract (NTS), the first relay in the central gustatory neuraxis, a rich
      variety of sensory inputs generated by active licking converge. Here, we show
      that taste responses in the NTS reflect these interactions. Experiments consisted
      of recordings of taste-related activity in the NTS of awake rats as they freely
      licked exemplars of the five basic taste qualities (sweet, sour, salty, bitter,
      umami). Nearly all taste-responsive cells were broadly tuned across taste
      qualities. A subset responded to taste with long latencies (>1.0 s), suggesting
      the activation of extraoral chemoreceptors. Analyses of the temporal
      characteristics of taste responses showed that spike timing conveyed
      significantly more information than spike count alone in almost one-half of NTS
      cells, as in anesthetized rats, but with less information per cell. In addition
      to taste-responsive cells, the NTS contains cells that synchronize with licks.
      Since the lick pattern per se can convey information, these cells may collaborate
      with taste-responsive cells to identify taste quality. Other cells become silent
      during licking. These latter "antilick" cells show a surge in firing rate
      predicting the beginning and signaling the end of a lick bout. Collectively, the
      data reveal a complex array of cell types in the NTS, only a portion of which
      include taste-responsive cells, which work together to acquire sensory
      information.

PMID- 22855800
TI  - Beneficial effects of Nrf2 overexpression in a mouse model of Alexander disease.
AB  - Alexander disease is a fatal neurodegenerative disease caused by dominant
      mutations in glial fibrillary acidic protein (GFAP). The disease is characterized
      by protein inclusions called Rosenthal fibers within astrocyte cell bodies and
      processes, and an antioxidant response mediated by the transcription factor Nrf2.
      We sought to test whether further elevation of Nrf2 would be beneficial in a
      mouse model of Alexander disease. Forcing overexpression of Nrf2 in astrocytes of
      R236H GFAP mutant mice decreased GFAP protein in all brain regions examined
      (olfactory bulb, hippocampus, cerebral cortex, brainstem, cerebellum, and spinal
      cord) and decreased Rosenthal fibers in olfactory bulb, hippocampus, corpus
      callosum, and brainstem. Nrf2 overexpression also restored body weights of R236H
      mice to near wild-type levels. Nrf2 regulates several genes involved in
      homeostasis of the antioxidant molecule glutathione, and the neuroprotective
      effects of Nrf2 in other neurological disorders may reflect restoration of
      glutathione to normal levels. However, glutathione levels in R236H mice were not
      decreased. Nrf2 overexpression did not change glutathione levels or ratio of
      reduced to oxidized glutathione (indicative of oxidative stress) in olfactory
      bulb, where Nrf2 dramatically reduced GFAP. Depletion of glutathione through
      knock-out of the GCLM (glutamate-cysteine ligase modifier subunit) also did not
      affect GFAP levels or body weight of R236H mice. These data suggest that the
      beneficial effects of Nrf2 are not mediated through glutathione.

PMID- 22855801
TI  - D1 receptor modulation of action potential firing in a subpopulation of layer 5
      pyramidal neurons in the prefrontal cortex.
AB  - Dopamine modulation in the prefrontal cortex is important for cognitive
      processing and disrupted in diverse neuropsychiatric diseases. Activation of D1
      receptors is thought to enable working memory by enhancing the firing properties
      of pyramidal neurons. However, these receptors are only sparsely expressed in the
      prefrontal cortex, and how they impact individual neurons remains unknown. Here
      we study D1 receptor modulation of layer 5 pyramidal neurons in acute slices of
      the mouse prefrontal cortex. Using whole-cell recordings and two-photon
      microscopy, we show that neurons expressing D1 receptors have unique
      morphological and physiological properties. We then demonstrate that activation
      of these receptors selectively enhances the firing of these neurons by signaling
      via the protein kinase A pathway. This finding of robust D1 receptor modulation
      in only a subpopulation of neurons has important implications for cognitive
      function and disease.

PMID- 22855802
TI  - Traveling waves on the organ of corti of the chinchilla cochlea: spatial
      trajectories of inner hair cell depolarization inferred from responses of
      auditory-nerve fibers.
AB  - Spatial magnitude and phase profiles for inner hair cell (IHC) depolarization
      throughout the chinchilla cochlea were inferred from responses of auditory-nerve
      fibers (ANFs) to threshold- and moderate-level tones and tone complexes. Firing
      rate profiles for frequencies <=2 kHz are bimodal, with the major peak at the
      characteristic place and a secondary peak at 3-5 mm from the extreme base.
      Response-phase trajectories are synchronous with peak outward stapes displacement
      at the extreme cochlear base and accumulate 1.5 period lags at the characteristic
      places. High-frequency phase trajectories are very similar to the trajectories of
      basilar-membrane peak velocity toward scala tympani. Low-frequency phase
      trajectories undergo a polarity flip in a region, 6.5-9 mm from the cochlear
      base, where traveling-wave phase velocity attains a local minimum and a local
      maximum and where the onset latencies of near-threshold impulse responses
      computed from responses to near-threshold white noise exhibit a local minimum.
      That region is the same where frequency-threshold tuning curves of ANFs undergo a
      shape transition. Since depolarization of IHCs presumably indicates the
      mechanical stimulus to their stereocilia, the present results suggest that
      distinct low-frequency forward waves of organ of Corti vibration are launched
      simultaneously at the extreme base of the cochlea and at the 6.5-9 mm transition
      region, from where antiphasic reflections arise.

PMID- 22855803
TI  - Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the
      murine auditory sensory epithelium.
AB  - Sox2 plays critical roles in cell fate specification during development and in
      stem cell formation; however, its role in postmitotic cells is largely unknown.
      Sox2 is highly expressed in supporting cells (SCs) of the postnatal mammalian
      auditory sensory epithelium, which unlike non-mammalian vertebrates remains
      quiescent even after sensory hair cell damage. Here, we induced the ablation of
      Sox2, specifically in SCs at three different postnatal ages (neonatal, juvenile
      and adult) in mice. In neonatal mice, Sox2-null inner pillar cells (IPCs, a
      subtype of SCs) proliferated and generated daughter cells, while other SC
      subtypes remained quiescent. Furthermore, p27(Kip1), a cell cycle inhibitor, was
      absent in Sox2-null IPCs. Similarly, upon direct deletion of p27(Kip1), p27(Kip1)
      null IPCs also proliferated but retained Sox2 expression. Interestingly, cell
      cycle control of IPCs by Sox2-mediated expression of p27(Kip1) gradually declined
      with age. In addition, deletion of Sox2 or p27(Kip1) did not cause a cell fate
      change. Finally, chromatin immunoprecipitation with Sox2 antibodies and
      luciferase reporter assays with the p27(Kip1) promoter support that Sox2 directly
      activates p27(Kip1) transcription in postmitotic IPCs. Hence, in contrast to the
      well known activity of Sox2 in promoting proliferation and cell fate
      determination, our data demonstrate that Sox2 plays a novel role as a key
      upstream regulator of p27(Kip1) to maintain the quiescent state of postmitotic
      IPCs. Our studies suggest that manipulating Sox2 or p27(Kip1) expression is an
      effective approach to inducing proliferation of neonatal auditory IPCs, an
      initial but necessary step toward restoring hearing in mammals.

PMID- 22855805
TI  - Unleashing potential: transcranial direct current stimulation over the right
      posterior parietal cortex improves change detection in low-performing
      individuals.
AB  - The limits of human visual short-term memory (VSTM) have been well documented,
      and recent neuroscientific studies suggest that VSTM performance is associated
      with activity in the posterior parietal cortex. Here we show that artificially
      elevating parietal activity via positively charged electric current through the
      skull can rapidly and effortlessly improve people's VSTM performance. This
      artificial improvement, however, comes with an interesting twist: it interacts
      with people's natural VSTM capability such that low performers who tend to
      remember less information benefitted from the stimulation, whereas high
      performers did not. This behavioral dichotomy is explained by event-related
      potentials around the parietal regions: low performers showed increased waveforms
      in N2pc and contralateral delay activity (CDA), which implies improvement in
      attention deployment and memory access in the current paradigm, respectively.
      Interestingly, these components are found during the presentation of the test
      array instead of the retention interval, from the parietal sites ipsilateral to
      the target location, thus suggesting that transcranial direct current stimulation
      (tDCS) was mainly improving one's ability to suppress no-change distractors
      located on the irrelevant side of the display during the comparison stage. The
      high performers, however, did not benefit from tDCS as they showed equally large
      waveforms in N2pc and CDA, or SPCN (sustained parietal contralateral negativity),
      before and after the stimulation such that electrical stimulation could not help
      any further, which also accurately accounts for our behavioral observations.
      Together, these results suggest that there is indeed a fixed upper limit in VSTM,
      but the low performers can benefit from neurostimulation to reach that maximum
      via enhanced comparison processes, and such behavioral improvement can be
      directly quantified and visualized by the magnitude of its associated
      electrophysiological waveforms.

PMID- 22855804
TI  - Movement-related changes in local and long-range synchronization in Parkinson's
      disease revealed by simultaneous magnetoencephalography and intracranial
      recordings.
AB  - Functional neurosurgery has afforded the opportunity to assess interactions
      between populations of neurons in the human cerebral cortex and basal ganglia in
      patients with Parkinson's disease (PD). Interactions occur over a wide range of
      frequencies, and the functional significance of those >30 Hz is particularly
      unclear. Do they improve movement, and, if so, in what way? We acquired
      simultaneously magnetoencephalography and direct recordings from the subthalamic
      nucleus (STN) in 17 PD patients. We examined the effect of synchronous and
      sequential finger movements and of the dopamine prodrug levodopa on induced power
      in the contralateral primary motor cortex (M1) and STN and on the coherence
      between the two structures. We observed discrete peaks in M1 and STN power at 60
      90 Hz and at 300-400 Hz. All these power peaks increased with movement and
      levodopa treatment. Only STN activity at 60-90 Hz was coherent with activity in
      M1. Directionality analysis showed that STN gamma activity at 60-90 Hz tended to
      drive gamma activity in M1. The effects of levodopa on both local and distant
      synchronization at 60-90 Hz correlated with the degree of improvement in
      bradykinesia-rigidity as did local STN activity at 300-400 Hz. Despite this,
      there were no effects of movement type, nor interactions between movement type
      and levodopa in the STN, nor in the coherence between STN and M1. We conclude
      that synchronization at 60-90 Hz in the basal ganglia cortical network is
      prokinetic but likely through a modulatory effect rather than any involvement in
      explicit motor processing.

PMID- 22855806
TI  - Experience-dependent switch in sign and mechanisms for plasticity in layer 4 of
      primary visual cortex.
AB  - Neural circuits are extensively refined by sensory experience during postnatal
      development. How the maturation of recurrent cortical synapses may contribute to
      events regulating the postnatal refinement of neocortical microcircuits remains
      controversial. Here we show that, in the main input layer of rat primary visual
      cortex, layer 4 (L4), recurrent excitatory synapses are endowed with multiple,
      developmentally regulated mechanisms for induction and expression of excitatory
      synaptic plasticity. Maturation of L4 synapses and visual experience lead to a
      sharp switch in sign and mechanisms for plasticity at recurrent excitatory
      synapses in L4 at the onset of the critical period for visual cortical
      plasticity. The state of maturation of excitatory pyramidal neurons allows
      neurons to engage different mechanisms for plasticity in response to the same
      induction paradigm. Experience is determinant for the maturation of L4 synapses,
      as well as for the transition between forms of plasticity and the mechanisms they
      may engage. These results indicate a tight correlation between the effects of
      sensory drive and maturation on cortical neurons and provide a new set of
      cellular mechanisms engaged in the postnatal refinement of cortical circuits.

PMID- 22855807
TI  - Strain background influences neurotoxicity and behavioral abnormalities in mice
      expressing the tetracycline transactivator.
AB  - The tet-off system has been widely used to create transgenic models of
      neurological disorders including Alzheimer's, Parkinson's, Huntington's, and
      prion disease. The utility of this system lies in the assumption that the
      tetracycline transactivator (TTA) acts as an inert control element and does not
      contribute to phenotypes under study. Here we report that neuronal expression of
      TTA can affect hippocampal cytoarchitecture and behavior in a strain-dependent
      manner. While studying neurodegeneration in two tet-off Alzheimer's disease
      models, we unexpectedly discovered neuronal loss within the dentate gyrus of
      single transgenic TTA controls. Granule neurons appeared most sensitive to TTA
      exposure during postnatal development, and doxycycline treatment during this
      period was neuroprotective. TTA-induced degeneration could be rescued by moving
      the transgene onto a congenic C57BL/6J background and recurred on reintroduction
      of either CBA or C3H/He backgrounds. Quantitative trait analysis of B6C3 F2 TTA
      mice identified a region on Chromosome 14 that contains a major modifier of the
      neurodegenerative phenotype. Although B6 mice were resistant to degeneration,
      they were not ideal for cognitive testing. F1 offspring of TTA C57BL/6J and
      129X1/SvJ, FVB/NJ, or DBA/1J showed improved spatial learning, but TTA expression
      caused subtle differences in contextual fear conditioning on two of these
      backgrounds, indicating that strain and genotype can interact independently under
      different behavioral settings. All model systems have limitations that should be
      recognized and mitigated where possible; our findings stress the importance of
      mapping the effects caused by TTA alone when working with tet-off models.

PMID- 22855809
TI  - Large-scale synchronized activity during vocal deviance detection in the zebra
      finch auditory forebrain.
AB  - Auditory systems bias responses to sounds that are unexpected on the basis of
      recent stimulus history, a phenomenon that has been widely studied using
      sequences of unmodulated tones (mismatch negativity; stimulus-specific
      adaptation). Such a paradigm, however, does not directly reflect problems that
      neural systems normally solve for adaptive behavior. We recorded multiunit
      responses in the caudomedial auditory forebrain of anesthetized zebra finches
      (Taeniopygia guttata) at 32 sites simultaneously, to contact calls that recur
      probabilistically at a rate that is used in communication. Neurons in secondary,
      but not primary, auditory areas respond preferentially to calls when they are
      unexpected (deviant) compared with the same calls when they are expected
      (standard). This response bias is predominantly due to sites more often not
      responding to standard events than to deviant events. When two call stimuli
      alternate between standard and deviant roles, most sites exhibit a response bias
      to deviant events of both stimuli. This suggests that biases are not based on a
      use-dependent decrease in response strength but involve a more complex mechanism
      that is sensitive to auditory deviance per se. Furthermore, between many
      secondary sites, responses are tightly synchronized, a phenomenon that is driven
      by internal neuronal interactions rather than by the timing of stimulus acoustic
      features. We hypothesize that this deviance-sensitive, internally synchronized
      network of neurons is involved in the involuntary capturing of attention by
      unexpected and behaviorally potentially relevant events in natural auditory
      scenes.

PMID- 22855808
TI  - Live-cell imaging evidence for the ciliary transport of rod photoreceptor opsin
      by heterotrimeric kinesin-2.
AB  - Primary cilia detect extracellular signals through membrane receptors and
      channels. The outer segment of a vertebrate photoreceptor cell represents the
      most elaborate of all primary cilia, containing extraordinarily large amounts of
      the visual receptor protein, opsin. Because of its high abundance, opsin
      represents a potential model system for the study of ciliary membrane receptors,
      including their transport. Here, we have analyzed the movement of ciliary opsin
      to test whether the highly conserved intraflagellar transport (IFT), as driven by
      heterotrimeric kinesin-2, is required. Results show that opsin can enter and move
      along the primary cilium of a nonphotoreceptor cell (an hTERT-RPE1 epithelial
      cell), suggesting that it can co-opt the basic anterograde motor system of cilia.
      Fluorescence recovery after photobleaching analysis of cilia of hTERT-RPE1 cells
      showed that the movement of ciliary opsin was comparable to that of the IFT
      protein, IFT88. Moreover, the movement of opsin in these cilia, as well as in
      cilia of mouse rod photoreceptor cells, was reduced significantly when KIF3A, the
      obligate motor subunit of heterotrimeric kinesin-2, was deficient. These studies
      therefore provide evidence from live-cell analysis that the conserved
      heterotrimeric kinesin-2 is required for the normal transport of opsin along the
      ciliary plasma membrane.

PMID- 22855810
TI  - A new concept: Abeta1-42 generates a hyperfunctional proteolytic NCX3 fragment
      that delays caspase-12 activation and neuronal death.
AB  - Although the amyloid-beta(1-42) (Abeta(1-42)) peptide involved in Alzheimer's
      disease is known to cause a dysregulation of intracellular Ca(2+) homeostasis,
      its molecular mechanisms still remain unclear. We report that the extracellular
      dependent early increase (30 min) in intracellular calcium concentration
      ([Ca(2+)](i)), following Abeta(1-42) exposure, caused the activation of calpain
      that in turn elicited a cleavage of the Na(+)/Ca(2+) exchanger isoform NCX3. This
      cleavage generated a hyperfunctional form of the antiporter and increased NCX
      currents (I(NCX)) in the reverse mode of operation. Interestingly, this NCX3
      calpain-dependent cleavage was essential for the Abeta(1-42)-dependent I(NCX)
      increase. Indeed, the calpain inhibitor calpeptin and the removal of the calpain
      cleavage recognition sequence, via site-directed mutagenesis, abolished this
      effect. Moreover, the enhanced NCX3 activity was paralleled by an increased
      Ca(2+) content in the endoplasmic reticulum (ER) stores. Remarkably, the
      silencing in PC-12 cells or the knocking-out in mice of the ncx3 gene prevented
      the enhancement of both I(NCX) and Ca(2+) content in ER stores, suggesting that
      NCX3 was involved in the increase of ER Ca(2+) content stimulated by Abeta(1-42).
      By contrast, in the late phase (72 h), when the NCX3 proteolytic cleavage
      abruptly ceased, the occurrence of a parallel reduction in ER Ca(2+) content
      triggered ER stress, as revealed by caspase-12 activation. Concomitantly, the
      late increase in [Ca(2+)](i) coincided with neuronal death. Interestingly, NCX3
      silencing caused an earlier activation of Abeta(1-42)-induced caspase-12. Indeed,
      in NCX3-silenced neurons, Abeta(1-42) exposure hastened caspase-dependent
      apoptosis, thus reinforcing neuronal cell death. These results suggest that
      Abeta(1-42), through Ca(2+)-dependent calpain activation, generates a
      hyperfunctional form of NCX3 that, by increasing Ca(2+) content into ER, delays
      caspase-12 activation and thus neuronal death.

PMID- 22855811
TI  - A fast and simple population code for orientation in primate V1.
AB  - Orientation tuning has been a classic model for understanding single-neuron
      computation in the neocortex. However, little is known about how orientation can
      be read out from the activity of neural populations, in particular in alert
      animals. Our study is a first step toward that goal. We recorded from up to 20
      well isolated single neurons in the primary visual cortex of alert macaques
      simultaneously and applied a simple, neurally plausible decoder to read out the
      population code. We focus on two questions: First, what are the time course and
      the timescale at which orientation can be read out from the population response?
      Second, how complex does the decoding mechanism in a downstream neuron have to be
      to reliably discriminate between visual stimuli with different orientations? We
      show that the neural ensembles in primary visual cortex of awake macaques
      represent orientation in a way that facilitates a fast and simple readout
      mechanism: With an average latency of 30-80 ms, the population code can be read
      out instantaneously with a short integration time of only tens of milliseconds,
      and neither stimulus contrast nor correlations need to be taken into account to
      compute the optimal synaptic weight pattern. Our study shows that-similar to the
      case of single-neuron computation-the representation of orientation in the spike
      patterns of neural populations can serve as an exemplary case for understanding
      the computations performed by neural ensembles underlying visual processing
      during behavior.

PMID- 22855812
TI  - Visual fixation as equilibrium: evidence from superior colliculus inactivation.
AB  - During visual fixation, the image of an object is maintained within the fovea.
      Previous studies have shown that such maintenance involves the deep superior
      colliculus (dSC). However, the mechanisms by which the dSC supports visual
      fixation remain controversial. According to one view, activity in the rostral dSC
      maintains gaze direction by preventing neurons in the caudal dSC from issuing
      saccade commands. An alternative hypothesis proposes that gaze direction is
      achieved through equilibrium of target position signals originating from the two
      dSCs. Here, we show in monkeys that artificially reducing activity in the rostral
      half of one dSC results in a biased estimate of target position during fixation,
      consistent with the second hypothesis, rather than an inability to maintain gaze
      fixation as predicted by the first hypothesis. After injection of muscimol at
      rostral sites in the dSC, fixation became more stable since microsaccade rate was
      reduced rather than increased. Moreover, the scatter of eye positions was offset
      relative to preinactivation baselines. The magnitude and the direction of the
      offsets depended on both the target size and the injected site in the collicular
      map. Other oculomotor parameters, such as the accuracy of saccades to peripheral
      targets and the amplitude and velocity of fixational saccades, were largely
      unaffected. These results suggest that the rostral half of the dSC supports
      visual fixation through a distributed representation of behaviorally relevant
      target position signals. The inactivation-induced fixation offset establishes the
      foveal visual stimulation that is required to restore the balance of activity
      between the two dSCs.

PMID- 22855813
TI  - Deconstructing the architecture of dorsal and ventral attention systems with
      dynamic causal modeling.
AB  - Attentional orientation to a spatial cue and reorientation-after invalid cueing
      are mediated by two distinct networks in the human brain. A bilateral dorsal
      frontoparietal network, comprising the intraparietal sulcus (IPS) and the frontal
      eye fields (FEF), controls the voluntary deployment of attention and may modulate
      visual cortex in preparation for upcoming stimulation. In contrast, reorienting
      attention to invalidly cued targets engages a right-lateralized ventral
      frontoparietal network comprising the temporoparietal junction (TPJ) and ventral
      frontal cortex. The present fMRI study investigated the functional architecture
      of these two attentional systems by characterizing effective connectivity during
      lateralized orienting and reorienting of attention, respectively. Subjects
      performed a modified version of Posner's location-cueing paradigm. Dynamic causal
      modeling (DCM) of regional responses in the dorsal and ventral network,
      identified in a conventional (SPM) whole-brain analysis, was used to compare
      different functional architectures. Bayesian model selection showed that top-down
      connections from left and right IPS to left and right visual cortex,
      respectively, were modulated by the direction of attention. Moreover, model
      evidence was highest for a model with directed influences from bilateral IPS to
      FEF, and reciprocal coupling between right and left FEF. Invalid cueing enhanced
      forward connections from visual areas to right TPJ, and directed influences from
      right TPJ to right IPS and IFG (inferior frontal gyrus). These findings shed
      further light on the functional organization of the dorsal and ventral
      attentional network and support a context-sensitive lateralization in the top
      down (backward) mediation of attentional orienting and the bottom-up (forward)
      effects of invalid cueing.

PMID- 22855814
TI  - Stepwise connectivity of the modal cortex reveals the multimodal organization of
      the human brain.
AB  - How human beings integrate information from external sources and internal
      cognition to produce a coherent experience is still not well understood. During
      the past decades, anatomical, neurophysiological and neuroimaging research in
      multimodal integration have stood out in the effort to understand the perceptual
      binding properties of the brain. Areas in the human lateral occipitotemporal,
      prefrontal, and posterior parietal cortices have been associated with sensory
      multimodal processing. Even though this, rather patchy, organization of brain
      regions gives us a glimpse of the perceptual convergence, the articulation of the
      flow of information from modality-related to the more parallel cognitive
      processing systems remains elusive. Using a method called stepwise functional
      connectivity analysis, the present study analyzes the functional connectome and
      transitions from primary sensory cortices to higher-order brain systems. We
      identify the large-scale multimodal integration network and essential
      connectivity axes for perceptual integration in the human brain.

PMID- 22855815
TI  - The stat3/socs3a pathway is a key regulator of hair cell regeneration in
      zebrafish. [corrected].
AB  - All nonmammalian vertebrates studied can regenerate inner ear mechanosensory
      receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993;
      Baird et al., 1996), but mammals possess only a very limited capacity for
      regeneration after birth (Roberson and Rubel, 1994). As a result, mammals
      experience permanent deficiencies in hearing and balance once their inner ear
      hair cells are lost. The mechanisms of hair cell regeneration are poorly
      understood. Because the inner ear sensory epithelium is highly conserved in all
      vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration
      mechanism in adult zebrafish, hoping the results would be transferrable to
      inducing hair cell regeneration in mammals. We defined the comprehensive network
      of genes involved in hair cell regeneration in the inner ear of adult zebrafish
      with the powerful transcriptional profiling technique digital gene expression,
      which leverages the power of next-generation sequencing ('t Hoen et al., 2008).
      We also identified a key pathway, stat3/socs3, and demonstrated its role in
      promoting hair cell regeneration through stem cell activation, cell division, and
      differentiation. In addition, transient pharmacological inhibition of stat3
      signaling accelerated hair cell regeneration without overproducing cells. Taking
      other published datasets into account (Sano et al., 1999; Schebesta et al., 2006;
      Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009),
      we propose that the stat3/socs3 pathway is a key response in all tissue
      regeneration and thus an important therapeutic target for a broad application in
      tissue repair and injury healing.

PMID- 22855817
TI  - Deciding when to decide: time-variant sequential sampling models explain the
      emergence of value-based decisions in the human brain.
AB  - The cognitive and neuronal mechanisms of perceptual decision making have been
      successfully linked to sequential sampling models. These models describe the
      decision process as a gradual accumulation of sensory evidence over time. The
      temporal evolution of economic choices, however, remains largely unexplored. We
      tested whether sequential sampling models help to understand the formation of
      value-based decisions in terms of behavior and brain responses. We used
      functional magnetic resonance imaging (fMRI) to measure brain activity while
      human participants performed a buying task in which they freely decided upon how
      and when to choose. Behavior was accurately predicted by a time-variant
      sequential sampling model that uses a decreasing rather than fixed decision
      threshold to estimate the time point of the decision. Presupplementary motor
      area, caudate nucleus, and anterior insula activation was associated with the
      accumulation of evidence over time. Furthermore, at the beginning of the decision
      process the fMRI signal in these regions accounted for trial-by-trial deviations
      from behavioral model predictions: relatively high activation preceded relatively
      early responses. The updating of value information was correlated with signals in
      the ventromedial prefrontal cortex, left and right orbitofrontal cortex, and
      ventral striatum but also in the primary motor cortex well before the response
      itself. Our results support a view of value-based decisions as emerging from
      sequential sampling of evidence and suggest a close link between the accumulation
      process and activity in the motor system when people are free to respond at any
      time.

PMID- 22855818
TI  - Purinergic modulation of neuronal activity in developing auditory brainstem.
AB  - In the developing nervous system, spontaneous neuronal activity arises
      independently of experience or any environmental input. This activity may play a
      major role in axonal pathfinding, refinement of topographic maps, dendritic
      morphogenesis, and the segregation of axonal terminal arbors. In the auditory
      system, endogenously released ATP in the cochlea activates inner hair cells to
      trigger bursts of action potentials (APs), which are transferred to the central
      auditory system. Here we show the modulatory role of purinergic signaling beyond
      the cochlea, i.e., the developmentally regulated and cell-type-specific
      depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We
      assessed the effects of P2X receptors (P2XRs) on neuronal excitability from
      prehearing to early stages of auditory signal processing. Our results demonstrate
      that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with
      Ca(2+) signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous
      and also acoustically evoked activity in vivo, but these effects diminish with
      maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also
      evoked APs in the absence of glutamatergic transmission. In vivo recordings also
      revealed that endogenously released ATP in the CN contributes to neuronal firing
      activity by facilitating AP generation and prolonging AP duration. Given the
      enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory
      brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable
      that purinergic signaling plays a specific role in the development of neuronal
      brainstem circuits.

PMID- 22855816
TI  - Cross-linking of cell surface amyloid precursor protein leads to increased beta
      amyloid peptide production in hippocampal neurons: implications for Alzheimer's
      disease.
AB  - The accumulation of the beta-amyloid peptide (Abeta) in Alzheimer's disease (AD)
      is thought to play a causative role in triggering synaptic dysfunction in
      neurons, leading to their eventual demise through apoptosis. Abeta is produced
      and secreted upon sequential cleavage of the amyloid precursor protein (APP) by
      beta-secretases and gamma-secretases. However, while Abeta levels have been shown
      to be increased in the brains of AD patients, little is known about how the
      cleavage of APP and the subsequent generation of Abeta is influenced, or whether
      the cleavage process changes over time. It has been proposed that Abeta can bind
      APP and promote amyloidogenic processing of APP, further enhancing Abeta
      production. Proof of this idea has remained elusive because a clear mechanism has
      not been identified, and the promiscuous nature of Abeta binding complicates the
      task of demonstrating the idea. To work around these problems, we used an
      antibody-mediated approach to bind and cross-link cell-surface APP in cultured
      rat primary hippocampal neurons. Here we show that cross-linking of APP is
      sufficient to raise the levels of Abeta in viable neurons with a concomitant
      increase in the levels of the beta-secretase BACE1. This appears to occur as a
      result of a sorting defect that stems from the caspase-3-mediated inactivation of
      a key sorting adaptor protein, namely GGA3, which prevents the lysosomal
      degradation of BACE1. Together, our data suggest the occurrence of a positive
      pathogenic feedback loop involving Abeta and APP in affected neurons possibly
      allowing Abeta to spread to nearby healthy neurons.

PMID- 22855819
TI  - Ablation of retinal horizontal cells from adult mice leads to rod degeneration
      and remodeling in the outer retina.
AB  - In the brain, including the retina, interneurons show an enormous structural and
      functional diversity. Retinal horizontal cells represent a class of interneurons
      that form triad synapses with photoreceptors and ON bipolar cells. At this first
      retinal synapse, horizontal cells modulate signal transmission from
      photoreceptors to bipolar cells by feedback and feedforward inhibition. To test
      how the fully developed retina reacts to the specific loss of horizontal cells,
      these interneurons were specifically ablated from adult mice using the diphtheria
      toxin (DT)/DT-receptor system and the connexin57 promoter. Following ablation,
      the retinal network responded with extensive remodeling: rods retracted their
      axons from the outer plexiform layer and partially degenerated, whereas cones
      survived. Cone pedicles remained in the outer plexiform layer and preserved
      synaptic contacts with OFF but not with ON bipolar cells. Consistently, the
      retinal ON pathway was impaired, leading to reduced amplitudes and prolonged
      latencies in electroretinograms. However, ganglion cell responses showed only
      slight changes in time course, presumably because ON bipolar cells formed
      multiple ectopic synapses with photoreceptors, and visual performance, assessed
      with an optomotor system, was only mildly affected. Thus, the loss of an entire
      interneuron class can be largely compensated even by the adult retinal network.

PMID- 22855820
TI  - A common neural mechanism for preventing and terminating the allocation of
      attention.
AB  - Much is known about the mechanisms by which attention is focused to facilitate
      perception, but little is known about what happens to attention after perception
      of the attended object is complete. One possibility is that the focus of
      attention passively fades. A second possibility is that attention is actively
      terminated after the completion of perception so that the brain can be prepared
      for the next target. The present study investigated this issue with event-related
      potentials in humans, focusing on the N2pc component (a neural measure of
      attentional deployment) and the Pd component (a neural measure of attentional
      suppression). We found that active suppression occurred both to prevent the
      allocation of attention to known distractors and to terminate attention after the
      perception of an attended object was complete. In addition, the neural measure of
      active suppression was correlated with a behavioral measure of trial-to-trial
      variations in the allocation of attention. Active suppression therefore appears
      to be a general-purpose mechanism that both prevents and terminates the
      allocation of attention.

PMID- 22855821
TI  - Neural correlates of the lombard effect in primate auditory cortex.
AB  - Speaking is a sensory-motor process that involves constant self-monitoring to
      ensure accurate vocal production. Self-monitoring of vocal feedback allows rapid
      adjustment to correct perceived differences between intended and produced
      vocalizations. One important behavior in vocal feedback control is a compensatory
      increase in vocal intensity in response to noise masking during vocal production,
      commonly referred to as the Lombard effect. This behavior requires mechanisms for
      continuously monitoring auditory feedback during speaking. However, the
      underlying neural mechanisms are poorly understood. Here we show that when
      marmoset monkeys vocalize in the presence of masking noise that disrupts vocal
      feedback, the compensatory increase in vocal intensity is accompanied by a shift
      in auditory cortex activity toward neural response patterns seen during
      vocalizations under normal feedback condition. Furthermore, we show that neural
      activity in auditory cortex during a vocalization phrase predicts vocal intensity
      compensation in subsequent phrases. These observations demonstrate that the
      auditory cortex participates in self-monitoring during the Lombard effect, and
      may play a role in the compensation of noise masking during feedback-mediated
      vocal control.

PMID- 22855822
TI  - Opposing effects of aging on large-scale brain systems for memory encoding and
      cognitive control.
AB  - Episodic memory declines with advancing age. Neuroimaging studies have associated
      such decline to age-related changes in general cognitive-control networks as well
      as to changes in process-specific encoding or retrieval networks. To assess the
      specific influence of aging on encoding and retrieval processes and associated
      brain systems, it is vital to dissociate encoding and retrieval from each other
      and from shared cognitive-control processes. We used multivariate partial-least
      squares to analyze functional magnetic resonance imaging data from a large
      population-based sample (n = 292, 25-80 years). The participants performed a face
      name paired-associates task and an active baseline task. The analysis revealed
      two significant network patterns. The first reflected a process-general encoding
      retrieval network that included frontoparietal cortices and posterior
      hippocampus. The second pattern dissociated encoding and retrieval networks. The
      anterior hippocampus was differentially engaged during encoding. Brain scores,
      representing whole-brain integrated measures of how strongly an individual
      recruited a brain network, were correlated with cognitive performance and
      chronological age. The scores from the general cognitive-control network
      correlated negatively with episodic memory performance and positively with age.
      The encoding brain scores, which strongly reflected hippocampal functioning,
      correlated positively with episodic memory performance and negatively with age.
      Univariate analyses confirmed that bilateral hippocampus showed the most
      pronounced activity reduction in older age, and brain structure analyses found
      that the activity reduction partly related to hippocampus atrophy. Collectively,
      these findings suggest that age-related structural brain changes underlie age
      related reductions in the efficient recruitment of a process-specific encoding
      network, which cascades into upregulated recruitment of a general cognitive
      control network.

PMID- 22855823
TI  - Role of rhodopsin and arrestin phosphorylation in retinal degeneration of
      Drosophila.
AB  - Arrestins belong to a family of multifunctional adaptor proteins that regulate
      internalization of diverse receptors including G-protein-coupled receptors
      (GPCRs). Defects associated with endocytosis of GPCRs have been linked to human
      diseases. We used enhanced green fluorescent protein-tagged arrestin 2 (Arr2) to
      monitor the turnover of the major rhodopsin (Rh1) in live Drosophila. We
      demonstrate that during degeneration of norpA(P24) photoreceptors the loss of Rh1
      is parallel to the disappearance of rhabdomeres, the specialized visual organelle
      that houses Rh1. The cause of degeneration in norpA(P24) is the failure to
      activate CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) and retinal
      degeneration C (RDGC) because of a loss of light-dependent Ca(2+) entry. A lack
      of activation in CaMKII, which phosphorylates Arr2, leads to hypophosphorylated
      Arr2, while a lack of activation of RDGC, which dephosphorylates Rh1, results in
      hyperphosphorylated Rh1. We investigated how reversible phosphorylation of Rh1
      and Arr2 contributes to photoreceptor degeneration. To uncover the consequence
      underlying a lack of CaMKII activation, we characterized ala(1) flies in which
      CaMKII was suppressed by an inhibitory peptide, and showed that morphology of
      rhabdomeres was not affected. In contrast, we found that expression of
      phosphorylation-deficient Rh1s, which either lack the C terminus or contain Ala
      substitution in the phosphorylation sites, was able to prevent degeneration of
      norpA(P24) photoreceptors. This suppression is not due to a loss of Arr2
      interaction. Importantly, co-expression of these modified Rh1s offered protective
      effects, which greatly delayed photoreceptor degeneration. Together, we conclude
      that phosphorylation of Rh1 is the major determinant that orchestrates its
      internalization leading to retinal degeneration.

PMID- 22855824
TI  - Interaction between alphaCaMKII and GluN2B controls ERK-dependent plasticity.
AB  - Understanding how brief synaptic events can lead to sustained changes in synaptic
      structure and strength is a necessary step in solving the rules governing
      learning and memory. Activation of ERK1/2 (extracellular signal regulated protein
      kinase 1/2) plays a key role in the control of functional and structural synaptic
      plasticity. One of the triggering events that activates ERK1/2 cascade is an NMDA
      receptor (NMDAR)-dependent rise in free intracellular Ca(2+) concentration.
      However the mechanism by which a short-lasting rise in Ca(2+) concentration is
      transduced into long-lasting ERK1/2-dependent plasticity remains unknown. Here we
      demonstrate that although synaptic activation in mouse cultured cortical neurons
      induces intracellular Ca(2+) elevation via both GluN2A and GluN2B-containing
      NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2
      phosphorylation. We show that alphaCaMKII, but not betaCaMKII, is critically
      involved in this GluN2B-dependent activation of ERK1/2 signaling, through a
      direct interaction between GluN2B and alphaCaMKII. We then show that interfering
      with GluN2B/alphaCaMKII interaction prevents synaptic activity from inducing ERK
      dependent increases in synaptic AMPA receptors and spine volume. Thus, in a
      developing circuit model, the brief activity of synaptic GluN2B-containing
      receptors and the interaction between GluN2B and alphaCaMKII have a role in long
      term plasticity via the control of ERK1/2 signaling. Our findings suggest that
      the roles that these major molecular elements have in learning and memory may
      operate through a common pathway.

PMID- 22855825
TI  - Neural selectivity and representation of gloss in the monkey inferior temporal
      cortex.
AB  - When we view an object, its appearance depends in large part on specific surface
      reflectance properties; among these is surface gloss, which provides important
      information about the material composition of the object and the fine structure
      of its surface. To study how gloss is represented in the visual cortical areas
      related to object recognition, we examined the responses of neurons in the
      inferior temporal (IT) cortex of the macaque monkey to a set of object images
      exhibiting various combinations of specular reflection, diffuse reflection, and
      roughness, which are important physical parameters of surface gloss. We found
      that there are neurons in the lower bank of the superior temporal sulcus that
      selectively respond to specific gloss. This neuronal selectivity was largely
      maintained when the shape or illumination of the object was modified and
      perceived glossiness was unchanged. By contrast, neural responses were
      significantly altered when the pixels of the images were randomly rearranged, and
      perceived glossiness was dramatically changed. The stimulus preference of these
      neurons differed from cell to cell, and, as a population, they systematically
      represented a variety of surface glosses. We conclude that, within the visual
      cortex, there are mechanisms operating to integrate local image features and
      extract information about surface gloss and that this information is
      systematically represented in the IT cortex, an area playing an important role in
      object recognition.

PMID- 22855826
TI  - Eeny meeny miny moe, catch a transcript by the toe, or how to enumerate
      eukaryotic transcripts.
AB  - In this issue of Genes & Development, Revyakin and colleagues (pp. 1691-1702)
      measure the relation between individual RNA polymerase II transcription events
      and transcription factor assembly by counting RNA transcripts retained on the
      template DNA using single-molecule fluorescence.

PMID- 22855827
TI  - Blunt-ended telomeres: an alternative ending to the replication and end
      protection stories.
AB  - Telomeres ensure the complete replication of genetic material while
      simultaneously distinguishing the chromosome terminus from a double-strand break.
      A prevailing theme in telomere biology is that the two chromosome ends are
      symmetrical. Both terminate in a single-strand 3' extension, and the 3' extension
      is crucial for telomere end protection. In this issue of Genes & Development,
      Kazda and colleagues (pp. 1703-1713) challenge this paradigm using a series of
      elegant biochemical and genetic assays to demonstrate that half of the
      chromosomes in flowering plants are blunt-ended. This discovery reveals
      unanticipated complexity in telomeric DNA processing and a novel mode of
      chromosome end protection.

PMID- 22855828
TI  - Regulation of dendritic branching by Cdc42 GAPs.
AB  - Nerve cells form elaborate, highly branched dendritic trees that are optimized
      for the receipt of synaptic signals. Recent work published in this issue of Genes
      & Development by Rosario and colleagues (pp. 1743-1757) shows that a Cdc42
      specific GTPase-activating protein (NOMA-GAP) regulates the branching of
      dendrites by neurons in the top layers of the mouse cortex. The results raise
      interesting questions regarding the specification of arbors in different cortical
      layers and the mechanisms of dendrite branching.

PMID- 22855830
TI  - Autoregulation of TDP-43 mRNA levels involves interplay between transcription,
      splicing, and alternative polyA site selection.
AB  - TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in
      mammals. Its expression is tightly autoregulated, with loss of this regulation
      implicated in human neuropathology. We demonstrate that TDP-43 overexpression in
      humans and mice activates a 3' untranslated region (UTR) intron, resulting in
      excision of the proximal polyA site (PAS) pA(1). This activates a cryptic PAS
      that prevents TDP-43 expression through a nuclear retention mechanism.
      Superimposed on this process, overexpression of TDP-43 blocks recognition of
      pA(1) by competing with CstF-64 for PAS binding. Overall, we uncover complex
      interplay between transcription, splicing, and 3' end processing to effect
      autoregulation of TDP-43.

PMID- 22855829
TI  - Condensins: universal organizers of chromosomes with diverse functions.
AB  - Condensins are multisubunit protein complexes that play a fundamental role in the
      structural and functional organization of chromosomes in the three domains of
      life. Most eukaryotic species have two different types of condensin complexes,
      known as condensins I and II, that fulfill nonoverlapping functions and are
      subjected to differential regulation during mitosis and meiosis. Recent studies
      revealed that the two complexes contribute to a wide variety of interphase
      chromosome functions, such as gene regulation, recombination, and repair. Also
      emerging are their cell type- and tissue-specific functions and relevance to
      human disease. Biochemical and structural analyses of eukaryotic and bacterial
      condensins steadily uncover the mechanisms of action of this class of highly
      sophisticated molecular machines. Future studies on condensins will not only
      enhance our understanding of chromosome architecture and dynamics, but also help
      address a previously underappreciated yet profound set of questions in chromosome
      biology.

PMID- 22855831
TI  - Unraveling the KNOTTED1 regulatory network in maize meristems.
AB  - KNOTTED1 (KN1)-like homeobox (KNOX) transcription factors function in plant
      meristems, self-renewing structures consisting of stem cells and their immediate
      daughters. We defined the KN1 cistrome in maize inflorescences and found that KN1
      binds to several thousand loci, including 643 genes that are modulated in one or
      multiple tissues. These KN1 direct targets are strongly enriched for
      transcription factors (including other homeobox genes) and genes participating in
      hormonal pathways, most significantly auxin, demonstrating that KN1 plays a key
      role in orchestrating the upper levels of a hierarchical gene regulatory network
      that impacts plant meristem identity and function.

PMID- 22855832
TI  - Cfp1 integrates both CpG content and gene activity for accurate H3K4me3
      deposition in embryonic stem cells.
AB  - Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised
      promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains
      the conserved subunit CxxC finger protein 1 (Cfp1), which binds to unmethylated
      CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays
      unanticipated roles in organizing genome-wide H3K4me3 in embryonic stem cells.
      Cfp1 deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at
      expressed CGI-associated genes, with minimal consequences for transcription, and
      creation of "ectopic" H3K4me3 peaks at numerous regulatory regions. DNA binding
      by Cfp1 was dispensable for targeting H3K4me3 to active genes but was required to
      prevent ectopic H3K4me3 peaks. The presence of ectopic peaks at enhancers often
      coincided with increased expression of nearby genes. This suggests that CpG
      targeting prevents "leakage" of H3K4me3 to inappropriate chromatin compartments.
      Our results demonstrate that Cfp1 is a specificity factor that integrates
      multiple signals, including promoter CpG content and gene activity, to regulate
      genome-wide patterns of H3K4me3.

PMID- 22855833
TI  - Biased transcription and selective degradation of small RNAs shape the pattern of
      DNA elimination in Tetrahymena.
AB  - The ciliated protozoan Tetrahymena undergoes extensive programmed DNA elimination
      when the germline micronucleus produces the new macronucleus during sexual
      reproduction. DNA elimination is epigenetically controlled by DNA sequences of
      the parental macronuclear genome, and this epigenetic regulation is mediated by
      small RNAs (scan RNAs [scnRNAs]) of ~28-30 nucleotides that are produced and
      function by an RNAi-related mechanism. Here, we examine scnRNA production and
      turnover by deep sequencing. scnRNAs are produced exclusively from the
      micronucleus and nonhomogeneously from a variety of chromosomal locations.
      scnRNAs are preferentially derived from the eliminated sequences, and this
      preference is mainly determined at the level of transcription. Despite this bias,
      a significant fraction of scnRNAs is also derived from the macronuclear-destined
      sequences, and these scnRNAs are degraded during the course of sexual
      reproduction. These results indicate that the pattern of DNA elimination in the
      new macronucleus is shaped by the biased transcription in the micronucleus and
      the selective degradation of scnRNAs in the parental macronucleus.

PMID- 22855836
TI  - Association between aortic valve calcification and myocardial ischemia,
      especially in asymptomatic patients.
AB  - Aortic valve calcification (AVC) is recognized as a manifestation of systemic
      arteriosclerosis. However, it is unclear whether AVC is associated with
      myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for
      the diagnosis of myocardial ischemia. However, routine MPS is not recommended,
      particularly in asymptomatic patients. Accordingly, we investigated the
      hypothesis that the presence of AVC is strongly associated with inducible
      myocardial ischemia, even among asymptomatic patients. METHODS: We investigated
      669 consecutive patients who underwent both adenosine stress (201)Tl MPS and
      echocardiography. We evaluated the extent and severity of myocardial ischemia by
      the summed difference score (SDS). We defined the presence of myocardial ischemia
      as SDS >= 3 and moderate to severe ischemia as SDS >= 8. We classified the
      severity of AVC according to the number of affected aortic leaflets. We also
      compared the mean SDS and the prevalence of SDS >= 3 and SDS >= 8 among patients
      stratified by the severity of AVC. RESULTS: The presence of AVC was significantly
      associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence
      interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16;
      95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly
      associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P =
      0.0043). However, the SDS value and the prevalence of SDS >= 3 and SDS >= 8 did
      not increase with increasing number of affected aortic leaflets. CONCLUSION: The
      presence of AVC may be associated with the presence of myocardial ischemia,
      particularly in asymptomatic patients. However, we found no association between
      the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a
      useful anatomic marker to help identify patients at high risk of myocardial
      ischemia, particularly asymptomatic patients.

PMID- 22855834
TI  - Context-specific roles for paracrine IL-6 in lymphomagenesis.
AB  - A basic requirement for the development of complex organ systems is that the
      cellular response to identical environmental cues can vary significantly between
      distinct cell types and developmental stages. While it is well established that
      paracrine signaling can similarly elicit diverse responses in distinct tumor
      types, the relevance of developmental stage-specific signaling responses to tumor
      development remains unclear. Here, we show that the same microenvironmental
      factor, IL-6, can both promote and prevent lymphoma development by acting on
      cells at distinct stages of hematopoietic development. Specifically, paracrine IL
      6 signaling promotes the survival of transplanted hematopoietic stem cells
      following lethal irradiation, allowing for the persistence and expansion of
      progenitor cells bearing a cancer-promoting alteration. Conversely, IL-6
      signaling also initiates a paracrine secretory program in the bone marrow that
      promotes B-cell differentiation and inhibits the development of B-cell
      malignancies. Thus, stage-specific responses to cytokines may promote progenitor
      cell expansion while also inhibiting neoplastic development within a single
      developmental lineage. Once transformed, the resulting B-cell lymphomas again use
      paracrine IL-6 signaling as a survival signal, highlighting the ability of tumor
      cells to co-opt pathways used for stem cell protection. These data not only
      suggest a complex regulation of tumor development by the preneoplastic
      microenvironment, but also that this regulation can decisively impact the outcome
      of well-established tumor modeling approaches.

PMID- 22855837
TI  - Targeted folate receptor beta fluorescence imaging as a measure of inflammation
      to estimate vulnerability within human atherosclerotic carotid plaque.
AB  - The probability of atherosclerotic plaque rupture and its thrombotic sequelae are
      thought to be increased at sites of macrophage accumulation. Folate receptor beta
      (FR-beta) is present on activated macrophages but not on quiescent macrophages or
      other immune cells. By conjugating the ligand folate with a fluorescent contrast
      agent, fluorescein isothiocyanate (FITC), we aimed to explore the potential role
      of FR-beta fluorescence imaging in the distinction of vulnerable sites from more
      stable regions. METHODS: Carotid specimens were taken from 20 patients and
      incubated with folate-FITC for 30 min. Ex vivo fluorescence imaging was performed
      to determine the exact location of folate-FITC uptake. Sections displaying
      regions of high uptake (determined as hot spots) were compared with sections
      showing low uptake (cold spots) through immunohistochemistry and real-time
      quantitative reverse-transcription polymerase chain reaction for FR-beta.
      RESULTS: Hot spots showed significantly higher folate-FITC uptake than cold spots
      (P < 0.001). Hot spots tended to contain more macrophages and areas of hypoxia
      than cold spots. A positive correlation between messenger RNA levels of CD68
      (marker for macrophages), FR-beta (r = 0.53, P = 0.045), and hypoxia-inducible
      factor-1alpha expression (marker for intraplaque hypoxia; r = 0.55, P = 0.034)
      was found. CONCLUSION: Compared with areas with low folate-FITC uptake, areas of
      high folate-FITC uptake within human atherosclerotic plaques had an increased
      number of activated macrophages and higher areas of hypoxia. These
      characteristics of vulnerability imply that molecular imaging of FR-beta through
      folate conjugates might be a good indicator for plaque vulnerability in future
      noninvasive imaging studies.

PMID- 22855840
TI  - The role of imaging physicians in industry.

PMID- 22855835
TI  - Contributions of mRNA abundance, ribosome loading, and post- or peri
      translational effects to temporal repression of C. elegans heterochronic miRNA
      targets.
AB  - miRNAs are post-transcriptional regulators of gene activity that reduce protein
      accumulation from target mRNAs. Elucidating precise molecular effects that animal
      miRNAs have on target transcripts has proven complex, with varied evidence
      indicating that miRNA regulation may produce different molecular outcomes in
      different species, systems, and/or physiological conditions. Here we use high
      throughput ribosome profiling to analyze detailed translational parameters for
      five well-studied targets of miRNAs that regulate C. elegans developmental
      timing. For two targets of the miRNA lin-4 (lin-14 and lin-28), functional down
      regulation was associated with decreases in both overall mRNA abundance and
      ribosome loading; however, these changes were of substantially smaller magnitude
      than corresponding changes observed in protein abundance. For three functional
      targets of the let-7 miRNA family for which down-regulation is critical in
      temporal progression of the animal (daf-12, hbl-1, and lin-41), we observed only
      modest changes in mRNA abundance and ribosome loading. lin-41 provides a striking
      example in that populations of ribosome-protected fragments from this gene
      remained essentially unchanged during the L3-L4 time interval when lin-41
      activity is substantially down-regulated by let-7. Spectra of ribosomal positions
      were also examined for the five lin-4 and let-7 target mRNAs as a function of
      developmental time, with no indication of miRNA-induced ribosomal drop-off or
      significant pauses in translation. These data are consistent with models in which
      physiological regulation by this set of C. elegans miRNAs derives from
      combinatorial effects including suppressed recruitment/activation of
      translational machinery, compromised stability of target messages, and post- or
      peri-translational effects on lifetimes of polypeptide products.

PMID- 22855841
TI  - R. Edward Coleman, MD, 1943-2012.

PMID- 22855843
TI  - Heightened DNA damage response impairs hematopoiesis in Fanconi anemia.

PMID- 22855844
TI  - Ligand-induced MET signaling as targetable codependence in acute myeloid
      leukemia.

PMID- 22855845
TI  - Infliximab therapy in hematologic malignancies: handle with care.

PMID- 22855847
TI  - Acute leukemia arising after radioiodine treatment for thyroid cancer.

PMID- 22855849
TI  - HSP90alpha deficiency does not affect immunoglobulin gene hypermutation and class
      switch but causes enhanced MHC class II antigen presentation.
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone required for efficient
      antigen presentation and cross-presentation. In addition, HSP90 was recently
      reported to interact with and stabilize the activation-induced cytidine deaminase
      (AID) and plays a critical role in immunoglobulin gene hypermutation and class
      switch recombination. In mice and humans, there are two HSP90 isoforms,
      HSP90alpha and HSP90beta, but the in vivo role of each isoform remains largely
      unknown. Here we have analyzed humoral immune responses in HSP90alpha-deficient
      mice. We found that HSP90alpha deficiency did not affect AID protein expression.
      B cell development and maturation, as well as immunoglobulin gene hypermuation
      and class switch, occurred normally in HSP90alpha-deficient mice. However,
      antibody production to a T-dependent antigen was elevated in the mutant mice and
      this was associated with enhanced MHC class II antigen presentation to T helper
      cells by dendritic cells. Our results reveal a previously unidentified inhibitory
      role for HSP90alpha isoform in MHC class II antigen presentation and the humoral
      immune response. Along with our recent finding that HSP90alpha is required for
      antigen cross-presentation, these results suggest that HSP90alpha controls the
      balance of humoral and cellular immunity by dictating the fate of presentation of
      exogenous antigen.

PMID- 22855850
TI  - The use of dual-mobility components in total hip arthroplasty.
AB  - Dual-mobility hip components provide for an additional articular surface, with
      the goal of improving range of motion, jump distance (ie, vertical or inferior
      head displacement required for dislocation), and stability of the total hip
      arthroplasty. A large polyethylene head articulates with a polished metal
      acetabular component, and an additional smaller metal head is snap-fit within the
      polyethylene. New components have recently been released for use in North
      America. Although these devices are routinely used in some European centers for
      primary hip arthroplasty, their greatest utility may be to manage recurrent
      dislocation in the setting of revision hip arthroplasty. Several small
      retrospective series have shown satisfactory results for this indication at short
      to midterm follow-up. Polyethylene wear and intraprosthetic dislocation are
      concerns, as is the lack of long-term data. Caution is thus advised in the
      routine use of dual-mobility components in primary and revision total hip
      arthroplasty.

PMID- 22855851
TI  - Total hip arthroplasty in the very young patient.
AB  - The surgical management of end-stage hip disease in patients aged <30 years
      remains a challenge. Hip-preserving surgical procedures in the setting of
      advanced disease often do not provide adequate pain relief, but the implications
      of joint arthroplasty surgery in the very young patient are a matter of concern.
      The outcome of total hip arthroplasty (THA) in these patients varies, largely
      because of the wide spectrum of diagnoses associated with hip disease in this
      group, the complexity of deformities requiring THA, and the need for prolonged
      durability. The greatest number of THAs in this population is performed for
      secondary osteoarthritis or osteonecrosis, whereas most reports in the
      orthopaedic literature have focused on the outcomes of cemented THA in patients
      with juvenile rheumatoid arthritis. Given the frequent complexity of THA in the
      very young patient, special attention should be given to preoperative planning,
      implant selection, and patient education as well as to joint-preservation
      techniques to facilitate future hip arthroplasty surgery.

PMID- 22855852
TI  - Displaced clavicle fractures in adolescents: facts, controversies, and current
      trends.
AB  - There is an increasing trend toward stabilization and fixation of markedly
      displaced midshaft clavicle fractures in adolescents. Recent studies in the adult
      literature have shown a greater prevalence of symptomatic malunion, nonunion, and
      poor functional outcomes after nonsurgical management of displaced fractures.
      Fixation of displaced midshaft clavicle fractures can restore length and
      alignment, resulting in shorter time to union. Symptomatic malunion after
      significantly displaced fractures in adolescents may be more common than
      previously thought. Adolescents often have high functional demands, and their
      remodeling potential is limited. Knowledge of bone biology and the effects of
      shortening, angulation, and rotation on shoulder girdle mechanics is critical in
      decision making in order to increase the likelihood of optimal results at
      skeletal maturity. Selection of fixation is dependent on many factors, including
      fracture type, patient age, skeletal maturity, and surgeon comfort.

PMID- 22855853
TI  - Nerve transfers for the upper extremity: new horizons in nerve reconstruction.
AB  - Nerve transfers are key components of the surgeon's armamentarium in brachial
      plexus and complex nerve reconstruction. Advantages of nerve transfers are that
      nerve regeneration distances are shortened, pure motor or sensory nerve fascicles
      can be selected as donors, and nerve grafts are generally not required. Similar
      to the principle of tendon transfers, expendable donor nerves are transferred to
      denervated nerves with the goal of functional recovery. Transfers may be
      subdivided into intraplexal, extraplexal, and distal types; each has a unique
      role in the reconstructive process. A thorough diagnostic workup and
      intraoperative assessment help guide the surgeon in their use. Nerve transfers
      have made a positive impact on the outcomes of nerve surgery and are essential
      tools in complex nerve reconstruction.

PMID- 22855854
TI  - Management of mid-season traumatic anterior shoulder instability in athletes.
AB  - Shoulder dislocation and subluxation injuries are common in young athletes and
      most frequently occur during the competitive season. Controversy exists regarding
      optimal treatment of an athlete with an in-season shoulder dislocation, and
      limited data are available to guide treatment. Rehabilitation may facilitate
      return to sport within 3 weeks, but return is complicated by a moderate risk of
      recurrence. Bracing may reduce the risk of recurrence, but it restricts motion
      and may not be tolerated in patients who must complete certain sport-specific
      tasks such as throwing. Surgical management of shoulder dislocation or
      subluxation with arthroscopic or open Bankart repair reduces the rate of
      recurrence; however, the athlete is unable to participate in sport for the
      remainder of the competitive season. When selecting a management option, the
      clinician must consider the natural history of shoulder instability, pathologic
      changes noted on examination and imaging, sport- and position-specific demands,
      duration of treatment, and the athlete's motivation.

PMID- 22855855
TI  - Degenerative lumbar spinal stenosis: evaluation and management.
AB  - Degenerative lumbar spinal stenosis is caused by mechanical factors and/or
      biochemical alterations within the intervertebral disk that lead to disk space
      collapse, facet joint hypertrophy, soft-tissue infolding, and osteophyte
      formation, which narrows the space available for the thecal sac and exiting nerve
      roots. The clinical consequence of this compression is neurogenic claudication
      and varying degrees of leg and back pain. Degenerative lumbar spinal stenosis is
      a major cause of pain and impaired quality of life in the elderly. The natural
      history of this condition varies; however, it has not been shown to worsen
      progressively. Nonsurgical management consists of nonsteroidal anti-inflammatory
      drugs, physical therapy, and epidural steroid injections. If nonsurgical
      management is unsuccessful and neurologic decline persists or progresses,
      surgical treatment, most commonly laminectomy, is indicated. Recent prospective
      randomized studies have demonstrated that surgery is superior to nonsurgical
      management in terms of controlling pain and improving function in patients with
      lumbar spinal stenosis.

PMID- 22855856
TI  - Orthogenomics: an update.
AB  - The study of genomics in orthopaedics has considerably lagged behind such study
      in other medical disciplines. Seminal work from other lines of medical research
      demonstrates the importance of genomic information in the evolution of
      personalized medicine. Common techniques for studying genome-phenotype
      associations include single nucleotide polymorphism, haplotype, and quantitative
      trait loci analysis. The few genome-based studies in major orthopaedic and
      related conditions have focused on osteoporosis, osteoarthritis, neuropathy and
      nerve compression, spinal deformity, trauma and inflammatory response, and pain
      and analgesia. The nascent field of orthogenomics, newly defined here as the
      application of genomic study to orthopaedic practice, has produced findings that
      could affect the practice of orthopaedics. However, more work is required, and
      the findings must be distilled and harnessed into applicable and achievable steps
      to improve clinical orthopaedic practice.

PMID- 22855857
TI  - Retrocyclin inhibits Gardnerella vaginalis biofilm formation and toxin activity.
AB  - BACKGROUND: Retrocyclins are cyclic antimicrobial peptides that have been shown
      to be both broadly active and safe in animal models. RC-101, a synthetic
      retrocyclin, targets important human pathogens and is a candidate vaginal
      microbicide. Its activity against microbes associated with bacterial vaginosis is
      unknown. METHODS: We investigated the effect of RC-101 on toxin activity,
      bacterial growth and biofilm formation of Gardnerella vaginalis in vitro.
      RESULTS: RC-101 potently inhibits the cytolytic activity of vaginolysin, the
      Gardnerella vaginalis toxin, on both erythrocytes and nucleated cells. RC-101
      lacks inhibitory activity against planktonic G. vaginalis but markedly decreases
      biofilm formation. CONCLUSIONS: These dual properties, toxin inhibition and
      biofilm retardation, justify further exploration of RC-101 as a candidate agent
      for bacterial vaginosis prevention.

PMID- 22855858
TI  - Carbapenemase-producing Enterobacteriaceae in Finland: the first years (2008-11).
AB  - OBJECTIVES: Carbapenemase-producing Enterobacteriaceae (CPE) are becoming a
      global problem; they are often resistant to nearly all available antibiotics.
      Here we report details on all Finnish CPE isolates found until the end of 2011:
      carbapenemase genes, travel history and multilocus sequence typing (MLST) data.
      METHODS: Enterobacteriaceae sent to the Antimicrobial Resistance Unit of the
      National Institute for Health and Welfare were tested for susceptibility to
      carbapenems, screened for carbapenemases by PCR and isolates with decreased
      susceptibility to carbapenems were tested for hydrolysis of imipenem.
      Carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolates were
      typed by MLST. RESULTS: In all, 26 CPE strains were found from 25 patients: 10
      with OXA-48-like enzymes, 5 with KPC, 4 with VIM, 3 with NDM, 3 with IMI/NMC-A
      and 1 with GES-14. The species were K. pneumoniae (n = 16), E. coli (n = 6),
      Enterobacter cloacae (n = 3) and Raoultella planticola (n = 1). Of the 25
      patients, 18 had a known travel history/hospital transfer from abroad. Local
      spread/transmission was suspected in 2011, but there were no hospital outbreaks.
      The K. pneumoniae multilocus sequence types ST258, ST182, ST147, ST244, ST14,
      ST13, ST383, ST101 and ST15, and the E. coli sequence types ST38 and ST90 were
      found. Many of these are global epidemic clones. CONCLUSIONS: CPE strains are
      increasingly found in Finland, but still at a very low prevalence.

PMID- 22855859
TI  - C-reactive protein in intracerebral hemorrhage: time course, tissue localization,
      and prognosis.
AB  - OBJECTIVES: We examined the C-reactive protein (CRP) response after spontaneous
      intracerebral hemorrhage (sICH) and its relationship to outcome. We additionally
      characterized early brain localization of CRP. METHODS: In this prospective,
      multicenter, international, collaborative, longitudinal study with cross
      sectional immunohistochemical analysis of brain tissue, 223 patients (M/F:
      132/91) were recruited during the 2010 calendar year. CRP was evaluated at
      admission (median 93 minutes from symptom onset), 24 hours, 48 hours, and 72
      hours after sICH. Brains of 5 subjects with sICH were compared to brains of 2
      aged controls without evidence of brain pathology and 7 patients with ischemic
      stroke. Plasma CRP was measured over 72 hours following sICH and its relationship
      to 30-day mortality and functional outcome at 30 days (Glasgow Outcome Scale) was
      determined. CRP immunostaining patterns were analyzed in samples of sICH autopsy
      brains. RESULTS: Plasma CRP increased over the 48 hours from admission and was
      significantly (p < 0.001) related to hematoma volume at later time points. The
      predictive utility of CRP for morbidity and mortality were maintained when
      adjusted for other risk factors and improved at 48 hours and 72 hours when
      compared with admission values. Although an early CRP localization was present in
      both ischemic and hemorrhagic lesions, an intense and diffuse neuropil staining
      was only present in sICH patients and particularly evident proximal to the
      hemorrhagic areas. CONCLUSIONS: Plasma CRP production increases markedly over the
      48 hours to 72 hours period following sICH and is related to outcome. CRP is also
      present in large amounts around the hemorrhagic lesion and within neurons and
      glia of patients who died within 12 hours of sICH.

PMID- 22855860
TI  - Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease.
AB  - OBJECTIVES: While plasma biomarkers have been proposed to aid in the clinical
      diagnosis of Alzheimer disease (AD), few biomarkers have been validated in
      independent patient cohorts. Here we aim to determine plasma biomarkers
      associated with AD in 2 independent cohorts and validate the findings in the
      multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Using a
      targeted proteomic approach, we measured levels of 190 plasma proteins and
      peptides in 600 participants from 2 independent centers (University of
      Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified
      17 analytes associated with the diagnosis of very mild dementia/mild cognitive
      impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C
      reactive protein, pancreatic polypeptide) were also found to be altered in
      clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF
      Abeta42 levels and t-tau/Abeta42 ratios to correlate with the number of APOE4
      alleles and plasma levels of B-type natriuretic peptide and pancreatic
      polypeptide. CONCLUSION: Four plasma analytes were consistently associated with
      the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts.
      These plasma biomarkers may predict underlying AD through their association with
      CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers
      needs to be confirmed in a prospective study.

PMID- 22855861
TI  - Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from
      multiple sclerosis.
AB  - OBJECTIVE: To investigate distinct white matter and cortical gray matter
      pathology in neuromyelitis optica spectrum disorders (NMOSDs) and multiple
      sclerosis (MS) at 7-T MRI in a cross-sectional study. METHODS: We included 10
      patients with NMOSDs and 18 patients with MS in our 7-T MRI study. The imaging
      protocol comprised T2*-weighted fast low angle shot and turbo inversion recovery
      magnitude sequences. White matter and cortical gray matter lesions were assessed
      with special regard to their (perivascular) localization as well as the
      expression of a hypointense rim. RESULTS: In total, we detected 140 white matter
      lesions in 7 of 10 patients with NMOSDs. In contrast to MS plaques, which were
      nearly exclusively centered by a small vein (92%) and showed a characteristic
      hypointense rim (23%), white matter changes in patients with NMOSDs were
      nonspecific in appearance and were only infrequently neighbored by a blood vessel
      (49 lesions [35%], p = 0.003). Hypointense rims were very rarely detectable (3
      lesions [2%], p < 0.001). Cortical pathology was absent in NMOSDs. In our MS
      cohort, we detected 36 leukocortical, 8 intracortical, and 8 subpial cortical
      lesions in 7 of 18 patients. CONCLUSION: The MRI features of white matter and the
      absence of cortical gray matter findings substantially differentiate NMOSDs from
      MS and can be used as a potential marker to distinguish these 2 entities. The
      fact that cortical pathology is common in MS but is not present in patients with
      NMOSDs may reflect the difference in the underlying pathogenesis.

PMID- 22855862
TI  - Antiplatelets vs anticoagulation for dissection: CADISS nonrandomized arm and
      meta-analysis.
AB  - OBJECTIVE: To present the results of the nonrandomized arm of the Cervical Artery
      Dissection in Stroke Study (CADISS-NR) trial, comparing anticoagulation and
      antiplatelets for prevention of recurrent stroke after carotid and vertebral
      dissection, and perform a meta-analysis of these results with previously
      published studies comparing the 2 therapeutic strategies. METHODS: A total of 88
      patients from 22 centers with extracranial carotid and vertebral dissection were
      recruited within 1 month of symptom onset. The primary endpoint was recurrent
      stroke at 3 months. A systematic review was performed, and results of published
      studies included in a meta-analysis with the CADISS-NR results. RESULTS: In
      CADISS-NR, one patient in each group had recurrent ischemic stroke (antiplatelet
      1/59 [1.69% ], anticoagulation 1/28 [3.57%]). At the primary endpoint of 3
      months, 3 (5.08%) antiplatelet patients had recurrent TIA, compared with none in
      the anticoagulation group. For meta-analysis, there were data from 40
      nonrandomized studies including 1,636 patients. There was no significant
      difference between the 2 treatments in recurrent stroke risk (antiplatelet 13/499
      [2.6%], anticoagulant 20/1,137 [1.8%], odds ratio [OR] 1.49) or risk of death
      (antiplatelet 5/499 [1.00%], anticoagulant 9/1,137 [0.80%], OR 1.27). CONCLUSION:
      There is no evidence for superiority of anticoagulation or antiplatelet therapy
      in prevention of stoke after carotid and vertebral artery dissection; however,
      all data are from nonrandomized studies and randomized studies are required. The
      nonrandomized CADISS data show a lower rate of recurrent stroke than reported in
      some previous studies. CLINICAL TRIAL REGISTRATION INFORMATION:
      www.dissection.co.uk, ISRNCTN44555237.

PMID- 22855864
TI  - Using blood markers for Alzheimer disease in clinical practice?

PMID- 22855863
TI  - Increased levels of acute-phase inflammatory proteins in plasma of patients with
      sporadic CJD.
AB  - OBJECTIVE: Screening plasma samples from patients with sporadic Creutzfeldt-Jakob
      disease (CJD) to discover diagnostic biomarkers. METHODS: Plasma samples were
      collected from 17 patients with sporadic CJD, 17 patients with Alzheimer disease
      (AD), and 20 healthy subjects. A 2-phase screening was carried out using
      quantitative protein mass spectrometry. The putative sporadic CJD biomarkers were
      then validated independently by immunoturbidimetry. RESULTS: Mass spectrometry
      uncovered 7 candidate sporadic CJD protein biomarkers, all belonging to the acute
      phase response. Highly significant increases of these markers in patients with
      sporadic CJD, compared with healthy subjects and patients with AD, was confirmed
      by immunoturbidimetry. CONCLUSIONS: The increase in plasma levels of a related
      set of acute-phase reactants in patients with sporadic CJD is a novel finding
      that suggests new pathogenetic hypotheses. The possible value of this set of
      proteins as biomarkers in the diagnosis of sporadic CJD or for blood/tissue donor
      screening remains to be further explored and validated in larger studies.

PMID- 22855865
TI  - Student assessment by objective structured examination in a neurology clerkship.
AB  - OBJECTIVES: We evaluated the reliability and predictive ability of an objective
      structured clinical examination (OSCE) in the assessment of medical students at
      the completion of a neurology clerkship. METHODS: We analyzed data from 195 third
      year medical students who took the OSCE. For each student, the OSCE consisted of
      2 standardized patient encounters. The scores obtained from each encounter were
      compared. Faculty clinical evaluations of each student for 2 clinical inpatient
      rotations were also compared. Hierarchical regression analysis was applied to
      test the ability of the averaged OSCE scores to predict standardized written
      examination scores and composite clinical scores. RESULTS: Students' OSCE scores
      from the 2 standardized patient encounters were significantly correlated with
      each other (r = 0.347, p < 0.001), and the scores for all students were normally
      distributed. In contrast, students' faculty clinical evaluation scores from 2
      different clinical inpatient rotations were uncorrelated, and scores were skewed
      toward the highest ratings. After accounting for clerkship order, better OSCE
      scores were predictive of better National Board of Medical Examiners standardized
      examination scores (R(2)Delta = 0.131, p < 0.001) and of better faculty clinical
      scores (R(2)Delta = 0.078, p < 0.001). CONCLUSIONS: Student assessment by an OSCE
      provides a reliable and predictive objective assessment of clinical performance
      in a neurology clerkship.

PMID- 22855867
TI  - CLIPPERS complicating multiple sclerosis causing concerns of CNS lymphoma.

PMID- 22855866
TI  - Caffeine for treatment of Parkinson disease: a randomized controlled trial.
AB  - OBJECTIVE: Epidemiologic studies consistently link caffeine, a nonselective
      adenosine antagonist, to lower risk of Parkinson disease (PD). However, the
      symptomatic effects of caffeine in PD have not been adequately evaluated.
      METHODS: We conducted a 6-week randomized controlled trial of caffeine in PD to
      assess effects upon daytime somnolence, motor severity, and other nonmotor
      features. Patients with PD with daytime somnolence (Epworth >10) were given
      caffeine 100 mg twice daily *3 weeks, then 200 mg twice daily *3 weeks, or
      matching placebo. The primary outcome was the Epworth Sleepiness Scale score.
      Secondary outcomes included motor severity, sleep markers, fatigue, depression,
      and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical
      models, adjusting for study site, baseline scores, age, and sex. RESULTS: Of 61
      patients, 31 were randomized to placebo and 30 to caffeine. On the primary
      intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in
      Epworth Sleepiness Scale score (-1.71 points; 95% confidence interval [CI] -3.57,
      0.13). However, somnolence improved on the Clinical Global Impression of Change
      (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth
      Sleepiness Scale score on per-protocol analysis (-1.97; -3.87, -0.05). Caffeine
      reduced the total Unified Parkinson's Disease Rating Scale score (-4.69 points; 
      7.7, -1.6) and the objective motor component (-3.15 points; -5.50, -0.83). Other
      than modest improvement in global health measures, there were no changes in
      quality of life, depression, or sleep quality. Adverse events were comparable in
      caffeine and placebo groups. CONCLUSIONS: Caffeine provided only equivocal
      borderline improvement in excessive somnolence in PD, but improved objective
      motor measures. These potential motor benefits suggest that a larger long-term
      trial of caffeine is warranted. CLASSIFICATION OF EVIDENCE: This study provides
      Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant
      benefit on excessive daytime sleepiness in patients with PD.

PMID- 22855868
TI  - Randomized clinical trial for geotropic horizontal canal benign paroxysmal
      positional vertigo.
AB  - OBJECTIVES: To determine the immediate and long-term therapeutic efficacies of
      barbecue rotation and Gufoni maneuvers, a randomized, prospective, and sham
      controlled study was conducted in patients with the geotropic type of benign
      paroxysmal positional vertigo involving the horizontal semicircular canal (HC
      BPPV). METHODS: In 10 nationwide dizziness clinics in Korea, 170 consecutive
      patients (107 women, age range 11-97 years, mean age +/- SD 61 +/- 15 years,
      median = 61 years) with geotropic HC-BPPV were randomly assigned to barbecue
      rotation (n = 56), Gufoni (n = 64), or sham maneuver (n = 50). An immediate
      response was determined within 1 hour after a maximum of 2 trials of each
      maneuver on the visit day. We also assessed the cumulative results of each
      maneuver by following up the patients for 1 month. RESULTS: After a maximum of 2
      maneuvers on the initial visit day, barbecue rotation (38 of 55 [69.1%]) and
      Gufoni (39 of 64 [60.9%]) maneuvers showed better responses than the sham
      maneuver (17 of 48 [35.4%]). The cumulative therapeutic effects were also better
      with barbecue rotation (p = 0.006) and Gufoni (p = 0.031) maneuvers than with the
      sham maneuver. However, therapeutic efficacies did not differ between the
      barbecue rotation and Gufoni groups in terms of both immediate (p = 0.46) and
      long-term (p = 0.10) outcomes. CONCLUSION: Using a prospective randomized trial,
      we demonstrated that barbecue rotation and Gufoni maneuvers are effective in
      treating geotropic HC-BPPV. CLASSIFICATION OF EVIDENCE: This study provides Class
      I evidence that barbecue rotation and Gufoni maneuvers are effective in the
      treatment of geotropic HC-BPPV.

PMID- 22855869
TI  - Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe.
AB  - OBJECTIVE: The long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) are potential candidates for interventions to delay
      Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at
      determining whether plasma levels of EPA or DHA predict atrophy of medial
      temporal lobe (MTL) gray matter regions in older subjects. METHODS: A total of
      281 community dwellers from the Three-City Study, aged 65 years or older, had
      plasma fatty acid measurements at baseline and underwent MRI examinations at
      baseline and at 4 years. We studied the association between plasma EPA and DHA
      and MTL gray matter volume change at 4 years. RESULTS: Higher plasma EPA, but not
      DHA, was associated with lower gray matter atrophy of the right
      hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise
      error corrected). Based on a mean right amygdala volume loss of 6.0 mm(3)/y
      (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline
      was related to a 1.3 mm(3) smaller gray matter loss per year in the right
      amygdala. Higher atrophy of the right amygdala was associated with greater 4-year
      decline in semantic memory performances and more depressive symptoms. CONCLUSION:
      The amygdala, which develops neuropathology in the early stage of AD and is
      involved in the pathogenesis of depression, may be an important brain structure
      involved in the association between EPA and cognitive decline and depressive
      symptoms.

PMID- 22855870
TI  - Caffeine in Parkinson disease: better for cruise control than snooze patrol?

PMID- 22855871
TI  - TMEM106B risk variant is implicated in the pathologic presentation of Alzheimer
      disease.

PMID- 22855872
TI  - Sporadic Creutzfeldt-Jakob disease: changes not only in the brain?

PMID- 22855873
TI  - Education of healthcare professionals and the public.
AB  - In the winter of 2007-08 a new public-facing antimicrobial campaign was agreed by
      the Advisory Committee on Antimicrobial Resistance and Healthcare-Associated
      Infection (ARHAI) Education sub-Group (later divided into subgroups for
      professional and public education): it comprised posters with a positive message
      on how the public could help themselves when they had a cold. However, the poster
      campaign, used in isolation in England, did not improve antibiotic use;
      therefore, the Public Education sub-Group took forward educational approaches to
      change the behaviour of the public and health professionals. Professionals have
      been encouraged to give patients clear information about the likely duration of
      symptoms, self-care, and benefits and harms of antibiotics, reinforcing the
      public poster campaigns in surgeries, hospitals and pharmacies. Since 2008,
      campaigns have been launched in England to coincide with European Antibiotic
      Awareness Day (EAAD) on 18 November, using Department of Health and EAAD
      materials. Professional education has been facilitated by the 2008 National
      Institute for Health and Clinical Excellence respiratory tract infection delayed
      prescribing guidance for general practitioners. A toolkit of materials for
      medicines management teams, to facilitate good antimicrobial stewardship in
      primary care (ASPIC), is being taken forward by the Public Education sub-Group
      and professional societies. After advice from ARHAI, in 2009 the General Medical
      Council requested that all postgraduate deans and Royal Colleges ensure infection
      prevention and control and antimicrobial prescribing become standard practice
      implemented in all clinical settings, and that they are emphasized strongly in
      undergraduate and postgraduate medical training. ARHAI has also taken a keen
      interest in reviewing, advising and leading on a number of European Union
      initiatives dealing with professional education.

PMID- 22855874
TI  - Policy development for Clostridium difficile.
AB  - The Advisory Committee on Antimicrobial Resistance and Healthcare Associated
      Infection (ARHAI) was created at the height of the incidence of Clostridium
      difficile infection (CDI). This article describes the role of ARHAI in the
      evaluation of laboratory testing for CDI, a related consultation on the legal
      requirements for manufacturers of in vitro diagnostic medical devices, a CDI
      healthcare bundle and surveillance of CDI in children.

PMID- 22855875
TI  - Recommendations for surveillance priorities for healthcare-associated infections
      and criteria for their conduct.
AB  - Surveillance and feedback of results to clinical teams is central to performance
      improvement in managing healthcare-acquired infections. A major role of the
      Advisory Committee on Antimicrobial Resistance and Healthcare-Associated
      Infections (ARHAI) is to advise on surveillance priorities. A sub-committee was
      set up to systematically review existing UK surveillance schemes. The following
      three systems were examined in detail: mandatory reporting of methicillin
      resistant Staphylococcus aureus (MRSA) bacteraemia and Clostridium difficile
      infection to the HPA; surveillance of surgical site infection undertaken by the
      HPA; and surgical site infection surveillance undertaken at University College
      London Hospital. Recommendations included the extension of mandatory reporting to
      include bacteraemia due to Escherichia coli and methicillin-susceptible S. aureus
      (MSSA), post-discharge surveillance of surgical site infection, the need for
      validation of surveillance systems and mandatory reporting of Caesarean section
      wound infections. Mandatory reporting of bacteraemia due to E. coli and MSSA were
      introduced during 2011 and further extension of surveillance is likely.

PMID- 22855876
TI  - Addressing healthcare-associated infections and antimicrobial resistance from an
      organizational perspective: progress and challenges.
AB  - This paper explores the progress and challenges associated with the application
      of organizational factors and approaches to infection prevention and control
      (IPC) and antibiotic stewardship (AS) in England, many of which have been
      considered and supported by the Advisory Committee on Antimicrobial Resistance
      and Healthcare-associated Infections (ARHAI). An organizational perspective is
      described and the wider macro context and socio-political forces that shape an
      organizational approach are considered. Factors that drive organizational change
      in IPC and AS are discussed. The tensions, constraints and dilemmas that can
      occur are identified and outstanding challenges are debated. Some recommendations
      for the future direction of IPC and AS organizationally focused strategies and
      research are proposed.

PMID- 22855877
TI  - Current challenges in antimicrobial resistance and healthcare-associated
      infections: role and organization of ARHAI.
AB  - The UK Government Specialist Advisory Committee on Antimicrobial Resistance and
      Healthcare-Associated Infections (ARHAI) was established in 2007. It has
      responsibility for providing practical and scientific advice to government on
      healthcare-associated infections (HCAIs) and to maintain the effectiveness of
      antimicrobial agents in the treatment and prevention of infection in man and
      animals. The manner in which this has been approached by ARHAI is described. In
      essence, key themes have been defined and issues dealt with through 'Focus
      Sessions', Subgroups and Working Groups. This Supplement reports on a selection
      of the key issues that have been addressed and the resulting recommendations and
      actions. Topics featured include: educational initiatives that target healthcare
      professionals and the public; methicillin-resistant Staphylococcus aureus and
      Clostridium difficile infections; surveillance priorities; healthcare management
      and HCAI and antimicrobial resistance (AMR); AMR in pathogens involving man and
      animals; technological innovation to support the control of AMR and HCAI;
      antimicrobial stewardship; and issues dealing with antiviral drug resistance.

PMID- 22855878
TI  - Working across the veterinary and human health sectors.
AB  - Antibiotics are widely used in human and veterinary medicine for the prevention
      and treatment of infectious diseases. This practice has led to the emergence of
      antimicrobial-resistant bacteria in both humans and animals. The potential role
      that animals, particularly livestock, might play as potential reservoirs of
      antibiotic resistance genes has been recognized, and it is currently a cause of
      public health concern. The impact of animal and human antibiotic usage on the
      emergence and persistence of resistant bacteria and the precise transfer pathways
      for resistance genes between humans and animals are not currently fully
      understood. As part of the remit of the UK Advisory Committee on Antimicrobial
      Resistance and Healthcare-Associated Infection (ARHAI), two main areas were
      addressed, namely methicillin-resistant Staphylococcus aureus (MRSA) and
      multidrug-resistant Gram-negative bacteria, where both the human and veterinary
      health sectors share interests. We review the current knowledge of MRSA and
      resistant Gram-negative bacteria, and provide guidance on occupational risks for
      veterinary healthcare workers relating to animals infected or colonized with
      MRSA. Findings and recommendations for further work across disciplines and future
      research in multidrug-resistant Gram-negative bacteria are also presented.
      Working collaboratively across disciplines is essential in order to better
      understand and challenge an important human and animal health problem:
      antimicrobial resistance.

PMID- 22855879
TI  - Improving the quality of antibiotic prescribing in the NHS by developing a new
      Antimicrobial Stewardship Programme: Start Smart--Then Focus.
AB  - There has been dramatic change in antibiotic use in English hospitals. Data from
      2004 and 2009 show that the focus on reducing fluoroquinolone and second- and
      third-generation cephalosporin use seems to have been heeded in NHS secondary
      care, and has been associated with a substantial decline in hospital Clostridium
      difficile rates. However, there has been a substantial increase in use of co
      amoxiclav, carbapenems and piperacillin/tazobactam. In primary care, antibiotic
      prescribing fell markedly from 1995 to 2000, but has since risen steadily to
      levels seen in the early 1990s. There remains a 2-fold variation in antimicrobial
      prescribing among English General Practices. In 2010, the NHS Atlas of Variation
      documented a 3-fold variation in the prescription of quinolones and an 18-fold
      variation in cephalosporins by Primary Care Trusts across England. There is a
      clear need to improve antimicrobial prescribing. This paper describes the
      development of new antimicrobial stewardship programmes for primary care and
      hospitals by the Department of Health's Advisory Committee on Antimicrobial
      Resistance and Healthcare Associated Infection: Antimicrobial Stewardship in
      Primary Care Initiative. The secondary care programme promotes the rapid
      prescription of the right antibiotic at the right dose at the right time,
      followed by active review for all patients still on antibiotics 48 h after
      admission. The five options available are to stop, switch to oral, continue and
      review again, change (if possible to a narrower spectrum) or move to outpatient
      parenteral antibiotic therapy. A range of audit and outcome tools has been
      developed, but to maintain optimal antimicrobial usage, monitoring of local and
      national quantitative and qualitative data on prescribing and consumption is
      required, linked to the development of key performance indicators in primary,
      secondary and tertiary care.

PMID- 22855880
TI  - ARHAI: antiviral resistance.
AB  - Development of antiviral resistance is a particular concern for the Advisory
      Committee on Antimicrobial Resistance and Healthcare-Associated Infections
      (ARHAI). Over the last 4 years, considerable time has been devoted to examining
      the ability of the UK to monitor the presence and transmission of antiviral
      resistance. Resistances to antiviral agents in influenza virus, HIV and hepatitis
      B and C viruses were identified as the main targets. The emphasis is on a network
      of laboratories that are able to perform diagnostic tests for resistance and to
      participate in surveillance programmes with co-ordination either through a
      central reference facility in the HPA or a collaborative study group.

PMID- 22855882
TI  - Assessing tobacco dependence among cannabis users smoking cigarettes.
AB  - INTRODUCTION: This study examines the relationship between nicotine exposure and
      tobacco addiction among young smokers consuming either only tobacco or only
      tobacco and cannabis. METHODS: Data on tobacco and cannabis use were collected by
      a questionnaire among 313 adolescents and young adults in Western Switzerland
      between 2009 and 2010. In addition, a urine sample was used to determine urinary
      cotinine level. Nicotine addiction was measured using the Fagerstrom Test for
      Nicotine Dependence (FTND). In this study, we focused on a sample of 142
      participants (mean age 19.54) that reported either smoking only tobacco
      cigarettes (CIG group, n = 70) or smoking both tobacco cigarettes and cannabis
      (CCS group, n = 72). RESULTS: The FTND did not differ significantly between CIG
      (1.96 +/- 0.26) and CCS (2.66 +/- 0.26) groups (p = 0.07). However, participants
      in the CCS group smoked more cigarettes (8.30 +/- 0.79 vs. 5.78 +/- 0.8, p =
      0.03) and had a higher mean cotinine value (671.18 +/- 67.6 vs. 404.32 +/- 68.63,
      p = 0.008) than the CIG group. Further, the association between cotinine and FTND
      was much stronger among the CIG than among the CCS group (regression coefficient
      of 0.0031 vs. 0.00099, p < 0.0001). CONCLUSION: Adolescents smoking tobacco and
      cannabis cigarettes featured higher levels of cotinine than youth smoking only
      tobacco; however, there was no significant difference in the addiction score. The
      FTND score is intended to measure nicotine dependence from smoked tobacco
      cigarettes. Hence, to accurately determine nicotine exposure and the associated
      dependence among young smokers, it seems necessary to inquire about cannabis
      consumption.

PMID- 22855883
TI  - FDA summary of adverse events on electronic cigarettes.

PMID- 22855884
TI  - Nicotine don't get no respect: a replication test.
AB  - INTRODUCTION: Although nicotine/tobacco use is the most prevalent, most deadly,
      and most treatable drug problem, a 1994 study by the author found that few
      scientific articles that generally discussed "drug/substance
      abuse/dependence/use" included nicotine as a focus. This analysis tested if this
      finding is still true in journals published in 2010-2011. METHOD: A random sample
      (n = 100) of articles whose titles used the term "drug/substance
      abuse/dependence/use" or "addiction" and did not refer to specific drugs in the
      2010-2011 issues of the 5 leading drug abuse/addiction journals. RESULTS: One
      fourth (25%) of these articles included nicotine/tobacco dependence/use or
      smoking as a focus, whereas 82% included alcohol or an illicit drug as a focus (p
      < .001). Only 3 articles (4%) mentioned the exclusion of tobacco/nicotine
      dependence/use. CONCLUSIONS: These results suggest most researchers consider
      nicotine/tobacco dependence/use to be different from other types of drug
      dependence. Whether nicotine is included when the term "drug/substance
      dependence/abuse/use" is used in a scientific article varies and could lead to
      confusion about the prevalence, harms, costs, treatment methods, etc. associated
      with drug use. The author recommends the use of the adjective "non-nicotine" when
      appropriate to avoid confusion.

PMID- 22855885
TI  - Smoking during consecutive pregnancies among primiparous women in the population
      based Norwegian Mother and Child Cohort Study.
AB  - INTRODUCTION: This study investigated changes in smoking behavior across
      pregnancies in a sample of 10,890 primiparous women participating in the
      prospective population-based Norwegian Mother and Child Cohort Study (MoBa) in
      order to identify risk factors that may inhibit smoking cessation and promote
      smoking during a woman's second pregnancy. METHODS: Registry information
      regarding smoking, age, marital status, parity, and year of birth was applied, in
      addition to questionnaire assessments of own and partner's smoking behavior,
      educational attainment, and symptoms of anxiety and depression at weeks 17 and 30
      of gestation from both pregnancies. RESULTS: The vast majority did not smoke in
      either of the pregnancies, and more women quit smoking than relapsed to smoking
      in their second pregnancy. Among smokers in the first pregnancy, 30.9% quit
      smoking by their second pregnancy. Women living with a nonsmoking partner or a
      partner who quit between pregnancies were more likely to quit smoking, as were
      women smoking occasionally in their first pregnancy. Symptoms of psychological
      distress and increasing number of years between pregnancies were negatively
      associated with smoking cessation. Among women not smoking in their first
      pregnancy, 2.3% did smoke during their second. Living with a smoking partner, low
      educational attainment, symptoms of psychological distress, and increasing number
      of years between pregnancies were all associated with smoking during the second
      pregnancy. CONCLUSIONS: These findings, linking smoking behavior to changes
      taking place between pregnancies, offer new and additional insight into
      modifiable risk factors that may help facilitate more targeted smoking cessation
      interventions for women at the highest risk.

PMID- 22855886
TI  - Germany SimSmoke: the effect of tobacco control policies on future smoking
      prevalence and smoking-attributable deaths in Germany.
AB  - INTRODUCTION: Although Germany has recently implemented some tobacco control
      policies, there is considerable scope to strengthen policies consistent with the
      MPOWER guidelines. This article describes the development of a simulation model
      projecting the effect of future tobacco control policies in Germany on smoking
      prevalence and associated premature mortality. METHODS: Germany SimSmoke-an
      adapted version of the SimSmoke simulation model of tobacco control policy-uses
      population, smoking rates, and policy data for Germany. It assesses, individually
      and in combination, the effect of seven types of policies: taxes, smoke-free air
      laws, mass media campaigns, advertising bans, warning labels, cessation
      treatment, and youth access policies. RESULTS: With a comprehensive set of
      policies, smoking prevalence within the first few years can be reduced by about
      22.0% relative to the status quo and by 37.9% (40.5%) for males (females) in 30
      years. By 2040, 39,548 deaths could be averted in that year alone. Without
      stronger policies, 700,000 additional smoking-attributable deaths (SADs) would
      occur in Germany over the next 30 years. CONCLUSIONS: The model indicates that
      the consequences of inaction are considerable; without the implementation of a
      stronger set of policies, smoking prevalence rates will remain relatively stable,
      and SADs among women will continue to rise over a 30-year horizon. Significant
      inroads into reducing smoking prevalence and premature mortality can be achieved
      through strengthening tobacco control policies in line with MPOWER
      recommendations.

PMID- 22855887
TI  - Risk factors and consequences of hyperaluminemia in a peritoneal dialysis cohort.
AB  - BACKGROUND: Widespread Al toxicity is unusual today. In 2005, Canadian peritoneal
      dialysis (PD) centers reported widespread hyperaluminemia in patients using
      dialysates from one specific manufacturer. Our objectives were to evaluate risk
      factors related to Al accumulation and to assess its clinical consequences in
      patients from 2 centers. METHODS: A retrospective closed cohort study was
      conducted in patients treated with PD in May 2005. A multivariate linear
      regression model was constructed to identify variables associated with a higher
      serum Al level in the exposed group at the moment of solution change. Using
      appropriate statistical methods, anemia and bone metabolism parameters were
      compared between the exposed and unexposed groups. Time to first peritonitis was
      estimated by the Kaplan-Meier method. RESULTS: The study cohort included 87 Al
      exposed patients and 95 unexposed patients. In the exposed group, serum Al at the
      moment of solution change was influenced by the length of exposure to Al
      containing dialysates and by PD creatinine clearance; serum Al was inversely
      correlated with renal creatinine clearance. No consequences of Al accumulation
      were observed. No difference was observed in the time to first peritonitis
      between patients who switched manufacturers and those who remained with the
      original manufacturer. CONCLUSIONS: Our results suggest that hyperaluminemia is
      directly related to the length and extent of exposure to Al-containing
      dialysates; residual renal function is protective against Al accumulation.
      Because the problem was detected rapidly, no clinical consequences of
      hyperaluminemia were observed in the study cohort.

PMID- 22855888
TI  - Clinical characteristics and outcomes of "silent" and "non-silent" peritonitis in
      patients on peritoneal dialysis.
AB  - OBJECTIVES: We compared the clinical characteristics and outcomes of "silent"
      peritonitis (meaning episodes without fever and abdominal pain) and "non-silent"
      peritonitis in patients on peritoneal dialysis (PD). METHODS: Our cohort study
      collected data about all peritonitis episodes occurring between January 2008 and
      April 2010. Disease severity score, demographics, and biochemistry and nutrition
      data were recorded at baseline. Effluent cell counts were examined at regular
      intervals, and the organisms cultured were examined. Treatment failure was
      defined as peritonitis-associated death or transfer to hemodialysis. RESULTS: Of
      248 episodes of peritonitis occurring in 161 PD patients, 20.9% led to treatment
      failure. Of the 248 episodes, 51 (20.6%) were not accompanied by fever and
      abdominal pain. Patients with these silent peritonitis episodes tended to be
      older (p = 0.003). The baseline values for body mass index, triglycerides, and
      daily energy intake were significantly lower before silent peritonitis episodes
      than before non-silent episodes (p = 0.01, 0.003, and 0.001 respectively).
      Although silent peritonitis episodes were more often culture-negative and less
      often caused by gram-negative organisms, and although they presented with low
      effluent white cell counts on days 1 and 3, the risk for treatment failure in
      those episodes was not lower (adjusted odds ratio: 1.33; 95% confidence interval:
      0.75 to 2.36; p = 0.33). CONCLUSIONS: Silent peritonitis is not a rare
      phenomenon, especially in older patients on PD. Although these episodes were more
      often culture-negative, silent presentation was not associated with a better
      outcome.

PMID- 22855889
TI  - Bacteria on catheters in patients undergoing peritoneal dialysis.
AB  - BACKGROUND: Peritonitis is the leading cause of morbidity for peritoneal dialysis
      (PD) patients, and microbial biofilms have previously been identified on
      catheters from infected patients. However, few studies of catheters from patients
      without clinical signs of infection have been undertaken. The aim of the present
      study was to investigate the extent to which bacteria are present on catheters
      from PD patients with no symptoms of infection. METHODS: Microbiologic culturing
      under aerobic and anaerobic conditions and confocal laser scanning microscopy
      were used to determine the distribution of bacteria on PD catheters from 15
      patients without clinical signs of infection and on catheters from 2 infected
      patients. The 16S rRNA gene sequencing technique was used to identify cultured
      bacteria. RESULTS: Bacteria were detected on 12 of the 15 catheters from patients
      without signs of infection and on the 2 catheters from infected patients. Single
      species and mixed-microbial communities containing up to 5 species were present
      on both the inside and the outside along the whole length of the colonized
      catheters. The bacterial species most commonly found were the skin commensals
      Staphylococcus epidermidis and Propionibacterium acnes, followed by S. warneri
      and S. lugdunensis. The strains of these micro-organisms, particularly those of
      S. epidermidis, varied in phenotype with respect to their tolerance of the major
      classes of antibiotics. CONCLUSIONS: Bacteria were common on catheters from
      patients without symptoms of infection. Up to 4 different bacterial species were
      found in close association and may represent a risk factor for the future
      development of peritonitis in patients hosting such micro-organisms.

PMID- 22855890
TI  - Predicting 12-month mortality for peritoneal dialysis patients using the
      "surprise" question.
AB  - BACKGROUND: Studies in hemodialysis patients suggest that the "surprise" question
      can help to identify a group of patients with a high mortality risk who should
      receive priority for palliative care interventions. However, the same instrument
      has not been tested in peritoneal dialysis (PD) patients. METHOD: We studied 367
      prevalent PD patients from a single dialysis center. Three clinicians
      independently answered the "surprise" question (Would I be surprised if this
      patient died within the next 12 months?) according to their clinical impression
      of the individual patient. Patients are then classified into "yes" (yes,
      surprised) and "no" (no, not surprised) groups. All patients were followed for 12
      months. RESULTS: In this cohort, 109 patients (29.7%) were allocated to the "no"
      group, and 258 (70.3%), to the "yes" group. Patients in the "no" group were older
      and had high prevalences of pre-existing ischemic heart disease, cerebrovascular
      disease, and peripheral vascular disease. The "no" group had a higher score on
      the Charlson comorbidity index and a higher malnutrition-inflammation score. At
      12 months, 44 patients had died. Mortality was 24.8% in the "no" group and 6.6%
      in the "yes" group. Multivariate analysis showed that an opinion of "Not
      surprised if dies in the next 12 months" was an independent predictor of 12-month
      mortality, with an associated 3.594 excess mortality risk (95% confidence
      interval: 1.411 to 9.151; p = 0.007). The positive predictive value of this
      opinion was 24.8%, and its negative predictive value was 93.4%. CONCLUSIONS: The
      "surprise" question has the potential to help identify a group of PD patients
      with high short-term mortality. Its use may contribute to a decision to refer PD
      patients for early palliative care assessment.

PMID- 22855892
TI  - Periodontitis and atherosclerotic vascular disease: what we know and why it is
      important.

PMID- 22855891
TI  - Leptin/adiponectin ratio is an independent predictor of mortality in nondiabetic
      peritoneal dialysis patients.
AB  - BACKGROUND: The leptin/adiponectin (L/A) ratio has been suggested to be an
      atherosclerotic index for diabetic patients and a useful marker of insulin
      resistance in patients with and without diabetes. Even though end-stage renal
      disease (ESRD) patients on peritoneal dialysis (PD) are well characterized by
      abnormal adipocytokine metabolism, the significance of alterations in the L/A
      ratio is largely unexplored in these patients. In this prospective study, we
      investigated the associations of leptin, adiponectin, and the L/A ratio with
      clinical outcomes in nondiabetic PD patients. METHODS: The study included 131
      stable nondiabetic ESRD patients who had been on PD for more than 3 months. Serum
      leptin and adiponectin levels were determined at baseline. Mortality was
      evaluated over a 5-year follow-up period. RESULTS: During the follow-up period,
      22 patients died (16.8%), including 10 (45.5%) as a result of cardiovascular
      disease. The L/A ratio showed a significant positive correlation with body mass
      index [BMI (r = 0.47, p < 0.001)], high-sensitivity C-reactive protein (r = 0.32,
      p < 0.001), and triglycerides (r = 0.43, p < 0.001). In addition, we observed
      significant inverse correlations between the L/A ratio and percentage lean body
      mass (r = -0.30, p = 0.001) and high-density lipoprotein cholesterol (r = -0.31,
      p = 0.001). In contrast to individual leptin and adiponectin levels, the L/A
      ratio was found to be independently associated with an increased mortality risk
      (relative risk: 1.15; 95% confidence interval: 1.05 to 1.27; p = 0.003) even
      after adjustments for age and BMI. CONCLUSIONS: The L/A ratio might be better
      related to patient outcomes than adipocytokines are individually in nondiabetic
      patients undergoing PD.

PMID- 22855893
TI  - Three-unit FDPs.

PMID- 22855895
TI  - Human trafficking.

PMID- 22855896
TI  - CBCT in orthodontics.

PMID- 22855898
TI  - The oral health status of 4,732 adults with intellectual and developmental
      disabilities.
AB  - BACKGROUND: Two reports by the U.S. surgeon general noted the disproportionate
      impact of oral disease on and lack of oral health information regarding people
      with disabilities. METHODS: In this retrospective study, the authors used
      clinical and demographic data (from April 1, 2009, through March 31, 2010) from
      electronic dental records of 4,732 adults with intellectual and developmental
      disabilities (IDDs) who were receiving dental care through a state-supported
      system of dental clinics. The authors used these data to investigate the oral
      health status of, and associated risk factors for, adults with IDD. RESULTS: The
      prevalence of untreated caries in the study population was 32.2 percent, of
      periodontitis was 80.3 percent and of edentulism was 10.9 percent. The mean
      (standard deviation) numbers of decayed teeth; missing teeth; and decayed,
      missing and filled teeth were 1.0 (2.2), 6.7 (7.0) and 13.9 (7.7), respectively.
      CONCLUSIONS: Management of oral health presents significant challenges in adults
      with IDD. Age, ability to cooperate with dental treatment and type of residence
      are important considerations in identifying preventive strategies. CLINICAL
      IMPLICATIONS: The study population demonstrated a high burden of dental disease.
      Further research is required to identify effective interventions to improve oral
      health in adults with IDD.

PMID- 22855899
TI  - The effectiveness of splint therapy in patients with temporomandibular disorders:
      a systematic review and meta-analysis.
AB  - PURPOSE: The authors conducted a systematic review of all published randomized
      controlled trials in which investigators compared the effectiveness of splint
      therapy with that of minimal or no treatment in patients with temporomandibular
      disorders (TMDs). TYPES OF STUDIES REVIEWED: The authors searched MEDLINE, Embase
      and the Cochrane Central Register of Controlled Trials for studies published from
      inception of each database through August 2011. In eligible studies,
      investigators enrolled adult patients with TMDs and assigned them randomly to
      splint therapy or a control group receiving minimal or no treatment. RESULTS: Of
      1,567 potentially eligible studies, 11 proved eligible and were included.
      Moderate-quality evidence suggests that splint therapy reduced pain in the
      temporomandibular joint (TMJ) area (standardized response mean = -0.93, 95
      percent confidence interval [CI], -1.33 to -0.53; risk difference for having
      continued pain = -0.35, 95 percent CI, -0.21 to -0.46; mean change on the 100
      millimeter visual analog scale = -11.5 mm, 95 percent CI, -16.5 mm to -6.6 mm).
      Low to very low quality of evidence showed no significant differences between the
      splint therapy and control groups in terms of quality of life or depression. None
      of the trial reports described effect on function. CONCLUSIONS: Although overall
      results are promising for the reduction of pain, establishing the role of splints
      for patients with TMDs will require large trials with stronger safeguards against
      bias.

PMID- 22855900
TI  - Pregnancy, breast-feeding and drugs used in dentistry.
AB  - BACKGROUND AND OVERVIEW: Despite advances in the study of birth defects related
      to drug exposures during pregnancy, medication use during pregnancy still causes
      anxiety and misunderstanding among both members of the public and health care
      professionals. This may result in a woman's unknowingly taking a medication that
      may harm the fetus or cause a birth defect or discontinuing medications necessary
      for treating chronic conditions. Using medications while breast-feeding also
      represents a challenge for patients and prescribers. Many mothers are told they
      must stop breast-feeding or "pump and discard" their breast milk if they are
      taking certain medications; however, in many cases, this advice-based on what may
      be limited education on the part of the health care provider about breast-feeding
      and medication use-may be incorrect. The authors review the current evidence
      regarding drugs that may be safe for pregnant or breast-feeding patients and
      medications that such patients should avoid. CONCLUSIONS: When considering
      prescribing in pregnancy, the dentist must weigh the risk to the fetus versus the
      benefit to the mother, and the appropriate conclusion should reflect current
      evidence. In some cases medication dosing should be avoided or altered; however,
      there are times when it is unnecessary to stop the use of medications. Breast
      feeding also represents a clinical challenge, the risks and benefits of which
      need to be understood by both the patient and practitioner before any medication
      is administered. PRACTICE IMPLICATIONS: Dentists should be familiar with the
      risks and benefits for pregnant or breast-feeding patients posed by five types of
      medications: analgesics and anti-inflammatories, antibiotics, local anesthetics,
      sedatives and emergency medications.

PMID- 22855901
TI  - The cardiovascular effects and pharmacokinetics of intranasal tetracaine plus
      oxymetazoline: preliminary findings.
AB  - BACKGROUND: The authors evaluated the cardiovascular effects and pharmacokinetics
      of an intranasal 3 percent tetracaine/0.05 percent oxymetazoline spray developed
      to provide needle-free anesthesia of maxillary teeth. METHODS: The authors
      administered to 12 participants a proposed maximum recommended dose (MRD) (18
      milligrams tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1
      milliliter nasal sprays. They administered two times this dose (36 mg
      tetracaine/0.6 mg oxymetazoline) as six bilateral pairs one to three weeks later.
      The authors recorded the patients' heart rate, blood pressure and oxygen
      saturation. They drew blood samples at baseline and 15 times during the two hours
      after drug administration. RESULTS: Physiological measures remained fairly stable
      throughout the two-hour period, with small but significant decreases (P < .05) in
      heart rate at 40 and 50 minutes for the two-times MRD (6.1 beats/minute) and MRD
      (7.5 beats/minute) administrations, respectively, and a significant increase in
      diastolic blood pressure (5.9 millimeters of mercury) for the two-times-MRD
      administration at 90 minutes. Mean oxygen saturation remained above 99 percent.
      Tetracaine plasma levels were undetectable in most participants, whereas
      concentrations of its major metabolite parabutylaminobenzoic acid from the two
      times-MRD administration were approximately twice that from the MRD
      administration. Oxymetazoline concentrations from the two-times-MRD
      administration were approximately 50 percent greater than those from the MRD
      administration, with a half-life of 1.72 to 2.32 hours. CONCLUSIONS: Intranasal
      tetracaine/oxymetazoline mist generally was well tolerated in study participants.
      CLINICAL IMPLICATIONS: The safety profile and pharmacokinetics of this intranasal
      formulation indicate that it appears to be generally well tolerated in patients
      for achieving anesthesia of the maxilla. Additional safety and efficacy data are
      required, particularly in patients with cardiovascular disease and other
      comorbidities.

PMID- 22855902
TI  - The first-choice standard of care for an edentulous mandible: a Delphi method
      survey of academic prosthodontists in the United States.
AB  - BACKGROUND: In 2002 and 2009, two consensus statements-one from a symposium in
      Canada and one from England-were issued that recommended that the first-choice
      standard of care for an edentulous mandible should be the two implant-retained
      mandibular overdenture (IRMOD). The authors conducted a survey to determine if,
      in 2011, U.S. academic prosthodontic experts' opinions were aligned with those in
      the two consensus statements. METHODS: The authors administered a Delphi method
      survey to an expert panel of 16 nationally representative academic
      prosthodontists to determine if there is consensus on the first-choice standard
      of care for an edentulous mandible between the IRMOD and a conventional
      mandibular complete denture (CD). Consensus agreement was defined as a 70 percent
      agreement level among the panelists. RESULTS: The panel attained consensus
      favoring the IRMOD for nine of the 10 parameters assessed-retention, stability,
      speech, masticatory efficiency, comfort while eating soft foods and hard foods,
      confidence in intimate situations, satisfaction and self-esteem. The exception
      was esthetics for which only a majority (51-69 percent) favored the IRMOD.
      CONCLUSIONS: The panelists reached consensus that they would recommend an IRMOD
      instead of a CD as the first-choice standard of care for patients who are healthy
      or have mild systemic disease, but not for patients with severe systemic disease.
      CLINICAL IMPLICATIONS: Surveyed academic prosthodontists recommend an IRMOD as
      the first choice standard of care when restoring an edentulous mandible of a
      healthy patient or a patient with mild systemic disease.

PMID- 22855903
TI  - The prevalence of substance use among patients at a dental school clinic in
      Michigan.
AB  - BACKGROUND: Problematic alcohol use and illicit drug use are associated with a
      number of physical health consequences, including poor oral health. The authors
      evaluate the prevalence of problematic alcohol use and illicit drug use in adults
      who visited a dental school clinic. METHODS: The authors recruited patients from
      the waiting area of the clinic. During recruitment, 85.9 percent of patients (n =
      384) who the authors approached consented to participate in the study. RESULTS:
      Overall, 20.6 percent of the participants reported either recent problematic
      alcohol use or illicit drug use; 7.4 percent of reported problematic alcohol use
      and 18.6 percent reported illicit drug use. The most common illicit drugs
      participants reported that they used were marijuana (16.8 percent), amphetamines
      (2.6 percent) and cocaine (1.1 percent). Participants who reported recent
      problematic alcohol use or illicit drug use were more likely to identify as
      white, were younger and did not have a spouse or partner. CONCLUSIONS: There was
      a high prevalence of illicit drug use and problematic alcohol use among the
      patients seen at dental school clinic. These rates were higher than those in the
      general population. CLINICAL IMPLICATIONS: The findings suggest that dental
      clinics are appropriate settings in which to identify and provide interventions
      for adults at risk of experiencing problems due to alcohol or drug use.

PMID- 22855904
TI  - Articaine is superior to lidocaine in providing pulpal anesthesia.

PMID- 22855905
TI  - The use of cone-beam computed tomography in dentistry: an advisory statement from
      the American Dental Association Council on Scientific Affairs.
AB  - BACKGROUND AND OVERVIEW: The American Dental Association Council on Scientific
      Affairs (CSA) promotes safe use of cone-beam computed tomography (CBCT) and
      appropriate professional justification of CBCT imaging procedures. The CSA
      reviewed the current research literature to develop collaborative guidance
      regarding the use of CBCT in dentistry with input from a broad group of
      stakeholder organizations. The Council's principles for CBCT safety may be
      applied to any number of potential dental CBCT imaging applications. PRACTICE
      IMPLICATIONS: As with other radiographic modalities, CBCT imaging should be used
      only after a review of the patient's health and imaging history and the
      completion of a thorough clinical examination. Dental practitioners should
      prescribe CBCT imaging only when they expect that the diagnostic yield will
      benefit patient care, enhance patient safety or improve clinical outcomes
      significantly.

PMID- 22855906
TI  - Why are dental implants not used more in the United States?

PMID- 22855907
TI  - 'Nudging' your patients toward improved oral health.
AB  - BACKGROUND: Behavioral economics combines research from the fields of psychology,
      neurology and economics to help people understand how people make choices in
      complex social and economic environments. The principles of behavioral economics
      increasingly are being applied in health care. The author describes how dental
      team members can use behavioral economics principles to improve patients' oral
      health. CONCLUSIONS: Dental patients must make complex choices about care, and
      dental team members must provide information to patients to help them make
      choices. Patients are subject to predictable biases and are prone to making
      errors. Dental team members can use this information to "nudge" patients in
      healthy directions by providing an appropriate mix of incentives, default options
      and feedback.  Practice Implications. The suggestions the author presents may
      help dental team members choose strategies that maximize both patient welfare and
      the success of their practices, while preserving patient autonomy.

PMID- 22855908
TI  - What is the ethical course of action for a dentist whose patient's previous
      dentist may have treated the wrong tooth?

PMID- 22855909
TI  - Neurosensory testing of orofacial pain in the dental clinic.

PMID- 22855910
TI  - The shear bond strength of resin-based composite to white mineral trioxide
      aggregate.
AB  - BACKGROUND: It is unknown if resin-based composite can be placed on top of
      mineral trioxide aggregate (MTA) immediately after placement of the MTA. The
      authors aimed to measure the bond strength of a resin-based composite to white
      MTA (WMTA) with different bonding strategies at different intervals. METHODS: The
      authors bonded resin-based composite to MTA with three bonding protocols (n = 45
      per group) (group 1, total-etching adhesive; group 2, two-step self-etching
      adhesive; or group 3, one-step self-etching adhesive), immediately (subgroup A),
      45 minutes (subgroup B) or 24 hours (subgroup C) after placement of the MTA. The
      authors measured shear bond strength by means of a universal testing machine and
      performed statistical analysis of the data by means of two-way and one-way
      analysis of variance (P < .05). RESULTS: In all three groups, subgroup A
      demonstrated greater bond strengths than the other subgroups. Group/subgroup 3/A
      demonstrated the highest bond strength (mean [standard deviation] 49.2 [2.1]
      megapascals), which was significantly higher than that in all other groups (P <
      .05). This was followed by group/subgroup 1/A (40.2 [2.5] MPa), 2/A (38.4 [1.3]
      MPa) and 1/B (38.5 [1.91] MPa). The lowest bond strength was shown by
      group/subgroup 2/C (14.7 [1.90] MPa). There was a significant difference between
      the two-step and one-step self-etching adhesives at all three intervals (P <
      .05). CONCLUSIONS: Within the limitations of this study, the representative one
      step self-etching adhesive demonstrated the strongest bond to WMTA immediately
      after fabrication of MTA samples. CLINICAL IMPLICATIONS: One-step self-etching
      adhesive may be used to bond resin-based composite to WMTA immediately after
      placement, thereby offsetting the need for a second appointment for permanent
      restoration.

PMID- 22855911
TI  - Cognitive performance and dehydration.
AB  - No matter how mild, dehydration is not a desirable condition because there is an
      imbalance in the homeostatic function of the internal environment. This can
      adversely affect cognitive performance, not only in groups more vulnerable to
      dehydration, such as children and the elderly, but also in young adults. However,
      few studies have examined the impact of mild or moderate dehydration on cognitive
      performance. This paper reviews the principal findings from studies published to
      date examining cognitive skills. Being dehydrated by just 2% impairs performance
      in tasks that require attention, psychomotor, and immediate memory skills, as
      well as assessment of the subjective state. In contrast, the performance of long
      term and working memory tasks and executive functions is more preserved,
      especially if the cause of dehydration is moderate physical exercise. The lack of
      consistency in the evidence published to date is largely due to the different
      methodology applied, and an attempt should be made to standardize methods for
      future studies. These differences relate to the assessment of cognitive
      performance, the method used to cause dehydration, and the characteristics of the
      participants.

PMID- 22855912
TI  - Effects of intentional weight loss on physical and cognitive function in middle
      aged and older obese participants: a pilot study.
AB  - OBJECTIVES: Obesity is a risk factor for cognitive decline and dementia. Whether
      weight loss improves cognition in older obese adults is not known. The objective
      was to investigate the effects of intentional weight loss on physical and
      cognitive function in middle-aged and older obese adults attending a weight loss
      clinic. METHOD: Eleven male and 39 female nonsmoking, adult obese (body mass
      index 30-50 kg/m(2)) participants were recruited. Participants were stratified by
      age: middle aged (30-59 years) and older aged (>= 60 years). The weight loss
      target for each subject was 8% to 12% of initial body weight. Information on
      anthropometry, bioelectrical impedance, hand-grip strength, Mini-Mental State
      Examination (MMSE), Short Portable Mental Status Questionnaire (SPMSQ), and Trail
      Making Test (TMT) A and B were collected at baseline and after weight loss.
      RESULTS: At baseline, older participants showed a nonsignificant trend for lower
      global cognitive function (MMSE, SPMSQ) and significantly slower processing speed
      (TMT-A). Twenty-one participants completed the weight loss study. The average
      weight loss relative to baseline was 9.7% +/- 2.1%. Weight loss was associated
      with significant improvements in hand-grip strength and cognitive function (MMSE,
      TMT-A, and TMT-B). MMSE scores improved significantly only in older obese
      participants (p < 0.05). CONCLUSIONS: Weight loss in middle-aged and in older
      obese participants has a beneficial effect on cognitive and physical function. If
      confirmed in future trials, weight loss can significantly affect public health
      strategies for the prevention of dementia as well as on the clinical management
      of obesity.

PMID- 22855913
TI  - Swiss children consuming breakfast regularly have better motor functional skills
      and are less overweight than breakfast skippers.
AB  - OBJECTIVE: The aim of this study was to examine the associations among eating
      behavior, body mass index (BMI), and motor functional skills in Swiss elementary
      school children. METHODS: In total, 656 schoolchildren, aged 7 to 10 years,
      participated in the study. Five different, normalized, and standardized motor
      function tests (sidewise jumping, tapping, standing long jump, 20-m sprint, and
      shuttle run) that determine the coordinative and conditional skills were carried
      out with each child at 1 of 4 time points (8, 9, 10, or 11 am) along with
      anthropometric measurements. Furthermore, all children completed a nutrition
      survey including different questions on their eating habits with emphasis on
      breakfast and the morning snack at school. RESULTS: Children consuming breakfast
      almost every day had a significantly (p < 0.05) lower BMI (16.7 +/- 2.2 kg/m2)
      compared with children eating breakfast only sometimes or almost never (18.2 +/-
      3.0 kg/m2 and 18.8 +/- 3.4 kg/m2, respectively). They also reached better scores
      in 3 of the 5 motor function tests (standing long jump, 20-m sprint, and shuttle
      run, p < 0.05). Furthermore, overweight and obese children reached poorer results
      in 4 disciplines of the motor functional tests (sidewise jumping, standing long
      jump, 20-m sprint, and shuttle run) than normal-weight children, and they tended
      to eat lunch and dinner more frequently in front of the TV or in their rooms (p <
      0.05). In multiple regression analysis, BMI was a significant predictor of the
      results for sprint, sidewise jumping, standing long jump, and shuttle run,
      whereas daytime, breakfast frequency, and gender predicted only some of the
      outcomes. CONCLUSION: This study clearly underlines the importance of breakfast
      for school-aged children: Children eating breakfast almost every day had better
      motor functional skills and a lower BMI than children not regularly eating
      breakfast. The study further hints at the importance of generally healthy
      nutritional habits with regard to both motor functional skills and healthy weight
      status.

PMID- 22855914
TI  - Ultrahigh-viscosity hydroxypropylmethylcellulose blunts postprandial glucose
      after a breakfast meal in women.
AB  - OBJECTIVE: To determine the effects of two water-soluble dietary fibers,
      ultrahigh-viscosity hydroxypropylmethylcellulose (UHV-HPMC, nonfermentable) and
      psyllium fiber (fermentable), on postprandial glucose and second meal effects.
      METHODS: In a single-blind crossover design, 12 healthy adult subjects were given
      standardized, premeasured breakfast and lunch meals with either 4 g of the fiber
      supplements or a placebo. Blood glucose was measured with a continuous blood
      glucose monitoring system (DexCom Seven Plus, San Diego, CA). RESULTS: Subjects
      consuming UHV-HPMC had significantly (p < 0.05) lower blood glucose area under
      the curve (AUC) 2 hours after breakfast than those receiving a placebo. Subjects
      consuming psyllium also tended to have lower glucose levels than the placebo
      group. Peak glucose concentration following breakfast was significantly (p <
      0.01) less with UHV-HPMC when compared with the placebo. No significant
      differences in AUC or peak glucose concentration between treatments following the
      second meal (lunch) were detected, suggesting no residual effect from the fiber
      supplements. CONCLUSIONS: Supplementation with viscous water-soluble fibers may
      be an effective means of reducing the glycemic response of a meal in healthy
      adults.

PMID- 22855915
TI  - The effect of soy protein beverages on serum cell adhesion molecule
      concentrations in prehypertensive/stage 1 hypertensive individuals.
AB  - OBJECTIVE: Prehypertensive and hypertensive individuals are at increased risk of
      atherosclerotic cardiovascular disease (CVD), in part because hypertension
      contributes to endothelial dysfunction and increased cell adhesion molecule
      expression. Soy protein and isoflavones may favorably alter CVD risk factors, and
      hence the aim of this study was to determine whether intake of cow's milk
      compared with soy beverage prepared from whole soy bean (WSB) or soy protein
      isolate (SPI) would lower soluble cell adhesion molecule concentrations as a
      means of decreasing CVD risk. METHODS: We enrolled healthy prehypertensive/stage
      1 hypertensive men (n = 60; 18-63 years) and premenopausal women (n = 8; 20-48
      years). Participants were randomized to 1 of 3 groups for 8 weeks: cow's milk
      (600 mL/d), SPI beverage (840 mL/d; 30.1 mg total isoflavones/d), or WSB beverage
      (840 mL/d; 91.4 mg total isoflavones/d). We measured soluble vascular cell
      adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1),
      and endothelial-leukocyte adhesion molecule-1 (E-selectin) concentrations at
      baseline and week 8. RESULTS: Soluble CAM concentrations were not altered by
      treatment and did not differ between prehypertensive and hypertensive
      participants. However, analysis of variance indicated a treatment * gender
      interaction (gender effect) for ICAM-1 (p = 0.0037) but not for E-selectin (p =
      0.067) or VCAM-1 (p = 0.16). Men had higher concentrations of ICAM-1 and E
      selectin, respectively, at baseline (p = 0.0071, p = 0.049) and week 8 (p =
      0.0054, p = 0.038) than women did. CONCLUSION: Neither intake of cow's milk nor
      soy beverage for 8 weeks altered soluble CAM concentrations in
      prehypertensive/stage 1 hypertensive individuals, suggesting that neither type of
      beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals
      by way of improving circulating CAM concentrations.

PMID- 22855916
TI  - Postprandial glycemia and appetite sensations in response to porridge made with
      rolled and pinhead oats.
AB  - OBJECTIVE: To determine the influence of porridge made with milk, honey, and
      either rolled oats (R) or pinhead oats (P) on postprandial glycemia and satiety.
      METHODS: Fifteen healthy participants were recruited, but because of
      noncompliance with the protocol, only 13 participants were included in the final
      analysis. In a randomized, crossover design, participants consumed porridge made
      with milk, water, honey, and either R or P. Finger-prick blood samples were taken
      at baseline and at 15, 30, 45, 60, 90, and 120 minutes following consumption of
      the porridge to determine blood glucose concentrations. Visual analog scales were
      used at the same time points to assess appetite sensations. Incremental area
      under the blood glucose concentration versus time curve (IAUC), ignoring area
      below the baseline, was used to assess glycemia. RESULTS: Porridge made with P
      reduced the blood glucose IAUC by 19.51 mmol/L * 120 minutes (95% confidence
      interval: 5.18, 33.84 mmol/L * 120 minutes; p = 0.012), although no differences
      in peak or time to peak blood glucose concentrations were observed (p = 0.603 and
      1.00, respectively). Hunger was not affected by the type of oats used (p =
      0.991), yet participants felt fuller following consumption of R compared with P
      (p = 0.024). CONCLUSIONS: Glycemia is improved yet feelings of fullness are
      attenuated following consumption of porridge made with P compared with R.

PMID- 22855917
TI  - Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in
      overweight and obese women with polycystic ovary syndrome: a randomized
      controlled intervention study.
AB  - OBJECTIVE: The recommended composition of a hypocaloric diet for obese women with
      polycystic ovary syndrome (PCOS) is unclear. The aim of this study was to
      investigate the effects of a high-protein, low-glycemic-load diet compared with a
      conventional hypocaloric diet on reproductive hormones, inflammatory markers,
      lipids, glucose, and insulin levels in obese women with PCOS. METHODS: A total of
      60 overweight and obese women with PCOS who did not use insulin-sensitizing
      agents were recruited and randomly assigned to 1 of the 2 hypocaloric diet groups
      for a single-blind clinical trial. The groups included a conventional hypocaloric
      diet (CHCD) (15% of daily energy from protein) and a modified hypocaloric diet
      (MHCD) with a high-protein, low-glycemic load (30% of daily energy from protein
      plus low-glycemic-load foods selected from a list) that was prescribed via
      counseling visits weekly during 12 weeks of study. Anthropometric assessments and
      biochemical measurements including reproductive hormones, inflammatory factors,
      lipids, glucose, and insulin were performed on fasting blood samples at baseline
      and after 12 weeks of dietary intervention. RESULTS: Weight loss was significant
      and similar in the 2 groups. Mean of testosterone in the MHCD and CHCD groups
      decreased from 1.78 +/- 0.32 to 1.31 +/- 0.26 ng/ml and from 1.51 +/- 0.12 to
      1.15 +/- 0.11 ng/ml, respectively (p < 0.001). Follicle sensitizing hormone
      (FSH), luteinizing hormone (LH), and blood lipids concentrations were not changed
      except low-density lipoprotein cholesterol (LDL-C) was reduced by 24.5% +/- 12.3%
      (p < 0.001 for both) after 12 weeks of intervention. MHCD resulted in a
      significant reduction in insulin level, homeostatic model assessment for insulin
      resistance (HOMA), and high-sensitivity C- reactive protein (hsCRP) concentration
      (p < 0.001). CONCLUSIONS: In this study both hypocaloric diets significantly led
      to reduced body weight and androgen levels in these two groups of women with
      PCOS. The combination of high-protein and low-glycemic-load foods in a modified
      diet caused a significant increase in insulin sensitivity and a decrease in hsCRP
      level when compared with a conventional diet.

PMID- 22855918
TI  - Evidence for the association between abdominal fat and cardiovascular risk
      factors in overweight and obese African American women.
AB  - OBJECTIVE: To determine the association between total body fat and abdominal
      region fat derived from dual-energy x-ray absorptiometry (DXA) scans and
      cardiovascular disease (CVD) risk factors in middle- to older-aged African
      American (AA) women. We also compared tape-measured waist and hip circumference
      and their ratio (WHR) with DXA measurements in the context of CVD risk factor
      predictability. METHODS: Participants included 59 overweight or obese African
      American women (age, 48.7 +/- 5.6 years). Anthropometries, including waist and
      hip circumferences, were measured, and DXA scans were used to derive fat mass
      from the total body and abdominal region. Blood analyses included glucose, total
      cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, total cholesterol/HDL and LDL/HDL ratios,
      C-reactive protein (CRP), and fibrinogen. Multiple linear regression models were
      used to investigate the association among DXA-derived fat mass measures, waist
      circumference, WHR, and cardiovascular risk factors. RESULTS: Among DXA-derived
      fat mass measures, DXA-derived abdominal fat mass showed the best prediction for
      glucose and triglycerides, although waist circumference and DXA-derived abdominal
      fat mass had equivalent capacity for predicting the total cholesterol/HDL ratio.
      Furthermore, waist circumference showed the best prediction for LDL/HDL ratio and
      CRP. CONCLUSIONS: Both DXA-derived abdominal fat mass and waist circumference had
      comparable capacity for predicting blood lipid profiles and CRP. Therefore, if
      waist circumference is measured correctly, it could be used as the simplest means
      of predicting CVD risk factors in overweight/obese AA women when DXA is not
      available.

PMID- 22855919
TI  - Determinants of weight loss after an intervention in low-income women in early
      postpartum.
AB  - OBJECTIVE: Postpartum is a critical period for the development of obesity in
      women, yet there is limited research of factors associated with changes in weight
      during early postpartum. Therefore, the objective of this study was to identify
      determinants of weight loss after an intervention. METHODS: A sample of women in
      early postpartum was recruited from the Special Supplemental Nutrition Program
      for Women, Infants, and Children clinics, doctors' offices, and neighborhood
      centers (N = 58). Women participated in an 8-week weight-loss intervention.
      Subjects were measured for weight and height and completed demographics, the
      Eating Stimulus Index, a nutrition knowledge test, a food-frequency
      questionnaire, and a household environment survey. Correlations and linear
      regression determined associations with the outcome variable weight loss, and
      hierarchical regression was used to determine the most significant predictors.
      RESULTS: All subjects improved their nutrition knowledge, skills, convenience
      eating resistance, and fruit and vegetable availability after the intervention.
      Responders had greater changes in dietary restraint, fruit juice servings, and
      discretionary energy than did nonresponders. Increases in dietary restraint,
      weight-management skills, and weight-loss self-efficacy and decreases in
      discretionary energy intake significantly predicted weight loss in individual
      regression analysis. After hierarchical regression analysis, improvement in
      dietary restraint was the most significant determinant, followed by decreases in
      total energy intake. Although weight-loss self-efficacy, weight-management
      skills, and discretionary energy intake significantly predicted weight loss when
      analyzed alone, these variables did not contribute to the prediction model
      revealed by this study. CONCLUSIONS: Positive changes in social cognitive theory
      constructs are associated with weight loss in low-income postpartum women.
      Dietary restraint, weight-management skills, weight loss self-efficacy, and
      reductions in total and discretionary energy are modifiable factors that should
      be emphasized in interventions designed for this population, but only dietary
      restraint and total energy intake were predicted in the model.

PMID- 22855921
TI  - Breastfeeding and maternal smoking.

PMID- 22855922
TI  - Breastfeeding and atopic dermatitis.

PMID- 22855923
TI  - Donor human milk for preterm infants.

PMID- 22855924
TI  - Policy statements on breastfeeding and human milk: additional comments.

PMID- 22855925
TI  - Varicella, influenza: not necessary to separate mother and infant.

PMID- 22855926
TI  - Vitamins.
AB  - * Based on strong research evidence, all infants should receive 400 IU/day of
      vitamin D beginning in the first few days of age to prevent vitamin D deficiency
      and rickets. * Based on strong research evidence, children and adolescents age >1
      year may require as much as 600IU/day of vitamin D. * Based on strong research
      evidence, all newborns should receive 1 mg of vitamin K at birth to prevent
      vitamin K deficiency bleeding. * Based on strong research evidence,
      preconceptional and pregnant women should be supplemented with folate to decrease
      the likelihood of neural tube defects.

PMID- 22855927
TI  - Patient safety and quality improvement: an overview of QI.
AB  - It is important for pediatric providers to be involved in quality improvement
      (QI) activities to improve children's health outcomes.* The Model for Improvement
      asks several key questions related to a process, then uses Plan-Do-Study
      Act(PDSA) cycles to implement, test, and spread changes.* Lean and Six Sigma
      methodologies can improve quality by increasing workflow efficiency and
      decreasing variation.* Root cause analysis (RCA) is a retrospective quality tool
      that helps determine factors contributing to errors and adverse events, so that
      improvements can be implemented.* Failure modes and effects analysis (FMEA) isa
      prospective quality tool that anticipates system vulnerabilities and helps
      develop risk reduction strategies.* Evidence-based interventions, such as best
      practice guidelines, promote standardization and reduce errors and adverse
      events, especially in high-risk health-care settings.* Team training can improve
      communication and situational awareness to create a safer health-care
      environment.

PMID- 22855928
TI  - Apparent life-threatening events: an update.
AB  - Based on strong research evidence, the most common causes of apparent life
      threatening events (ALTEs) are gastroesophageal reflux, lower respiratory tract
      infection, and seizure. * The minimum initial diagnostic panel for ALTE should
      include complete blood cell (CBC) count with differential; blood levels of C
      reactive protein,glucose, sodium, potassium, urea, calcium,magnesium, ammonia,
      lactate, and pyruvate; arterial blood gas determination, urinalysis, and
      toxicology screen; electrocardiography; and assessments for Bordetella pertussis
      and respiratory syncytial virus in season. * Other testing should be done based
      on the infant's clinical presentation and clinician's degree of suspicion.* Most
      infants should be hospitalized for cardiorespiratory monitoring for 23 hours
      after an ALTE. * There is strong evidence that newborns are at higher risk of
      ALTE and sudden infant death syndrome (SIDS)within the first 24 hours after birth
      and therefore should be frequently monitored as much as possible while room
      sharing with their mothers. * Evidence suggests that maternal smoking may place
      an infant for higher risk of SIDS after an ALTE.

PMID- 22855929
TI  - Bioethics education and resources.
AB  - Ethics education based upon everyday ethical dilemmas can help trainees place
      themselves within the situation and encourage them to reflect on their role and
      responsibility in reaching its resolution.* Three elements can help augment the
      bioethics teaching experience: (a) identifying the ethical dilemma, (b) employing
      methods of ethical analysis, and(c) having knowledge of additional bioethics
      resources.An increasing number of bioethics resources are available to
      clinicians, including clinical ethics consultation (CEC) and print and Web-based
      resources.

PMID- 22855930
TI  - Behind the screen: responding to intimate partner violence.

PMID- 22855932
TI  - Index of suspicion.

PMID- 22855933
TI  - Posttraumatic stress disorder.

PMID- 22855935
TI  - A 6-year-old girl with restricted upward gaze of her right eye.
AB  - Brown syndrome is an incomitant strabismus syndrome characterized by inability of
      the eye to elevate during adduction. * Primary Brown syndrome is thought to occur
      due to the inability of the superior oblique tendon to stretch.However, there are
      many secondary causes of this condition that must be ruled out. * Despite
      significant misalignment of the eyes during upgaze, patients with Brown syndrome
      usually do not have decreased vision or diplopia with primary gaze. * Unlike
      paralytic strabismus, forced duction tests demonstrate restriction and a Parks'
      three-step test does not demonstrate a paralytic muscle. Spontaneous resolution
      is frequent, and surgical management typically is not indicated because of the
      high incidence of postoperative symptomatic superior oblique palsy.

PMID- 22855936
TI  - MdCOP1 ubiquitin E3 ligases interact with MdMYB1 to regulate light-induced
      anthocyanin biosynthesis and red fruit coloration in apple.
AB  - MdMYB1 is a crucial regulator of light-induced anthocyanin biosynthesis and fruit
      coloration in apple (Malus domestica). In this study, it was found that MdMYB1
      protein accumulated in the light but degraded via a ubiquitin-dependent pathway
      in the dark. Subsequently, the MdCOP1-1 and MdCOP1-2 genes were isolated from
      apple fruit peel and were functionally characterized in the Arabidopsis
      (Arabidopsis thaliana) cop1-4 mutant. Yeast (Saccharomyces cerevisiae) two
      hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation
      assays showed that MdMYB1 interacts with the MdCOP1 proteins. Furthermore, in
      vitro and in vivo experiments indicated that MdCOP1s are necessary for the
      ubiquitination and degradation of MdMYB1 protein in the dark and are therefore
      involved in the light-controlled stability of the MdMYB1 protein. Finally, a
      viral vector-based transformation approach demonstrated that MdCOP1s negatively
      regulate the peel coloration of apple fruits by modulating the degradation of the
      MdMYB1 protein. Our findings provide new insight into the mechanism by which
      light controls anthocyanin accumulation and red fruit coloration in apple and
      even other plant species.

PMID- 22855939
TI  - [More artemisinin-resistant malaria in Thailand].

PMID- 22855937
TI  - Plasma membrane localization of Solanum tuberosum remorin from group 1, homolog 3
      is mediated by conformational changes in a novel C-terminal anchor and required
      for the restriction of potato virus X movement].
AB  - The formation of plasma membrane (PM) microdomains plays a crucial role in the
      regulation of membrane signaling and trafficking. Remorins are a plant-specific
      family of proteins organized in six phylogenetic groups, and Remorins of group 1
      are among the few plant proteins known to specifically associate with membrane
      rafts. As such, they are valuable to understand the molecular bases for PM
      lateral organization in plants. However, little is known about the structural
      determinants underlying the specific association of group 1 Remorins with
      membrane rafts. We used a structure-function approach to identify a short C
      terminal anchor (RemCA) indispensable and sufficient for tight direct binding of
      potato (Solanum tuberosum) REMORIN 1.3 (StREM1.3) to the PM. RemCA switches from
      unordered to alpha-helical structure in a nonpolar environment. Protein structure
      modeling indicates that RemCA folds into a tight hairpin of amphipathic helices.
      Consistently, mutations reducing RemCA amphipathy abolished StREM1.3 PM
      localization. Furthermore, RemCA directly binds to biological membranes in vitro,
      shows higher affinity for Detergent-Insoluble Membranes lipids, and targets
      yellow fluorescent protein to Detergent-Insoluble Membranes in vivo. Mutations in
      RemCA resulting in cytoplasmic StREM1.3 localization abolish StREM1.3 function in
      restricting potato virus X movement. The mechanisms described here provide new
      insights on the control and function of lateral segregation of plant PM.

PMID- 22855940
TI  - [Meeting with the holy in clinical practice].

PMID- 22855938
TI  - Expansive evolution of the trehalose-6-phosphate phosphatase gene family in
      Arabidopsis.
AB  - Trehalose is a nonreducing sugar used as a reserve carbohydrate and stress
      protectant in a variety of organisms. While higher plants typically do not
      accumulate high levels of trehalose, they encode large families of putative
      trehalose biosynthesis genes. Trehalose biosynthesis in plants involves a two
      step reaction in which trehalose-6-phosphate (T6P) is synthesized from UDP
      glucose and glucose-6-phosphate (catalyzed by T6P synthase [TPS]), and
      subsequently dephosphorylated to produce the disaccharide trehalose (catalyzed by
      T6P phosphatase [TPP]). In Arabidopsis (Arabidopsis thaliana), 11 genes encode
      proteins with both TPS- and TPP-like domains but only one of these (AtTPS1)
      appears to be an active (TPS) enzyme. In addition, plants contain a large family
      of smaller proteins with a conserved TPP domain. Here, we present an in-depth
      analysis of the 10 TPP genes and gene products in Arabidopsis (TPPA-TPPJ).
      Collinearity analysis revealed that all of these genes originate from whole
      genome duplication events. Heterologous expression in yeast (Saccharomyces
      cerevisiae) showed that all encode active TPP enzymes with an essential role for
      some conserved residues in the catalytic domain. These results suggest that the
      TPP genes function in the regulation of T6P levels, with T6P emerging as a novel
      key regulator of growth and development in higher plants. Extensive gene
      expression analyses using a complete set of promoter-beta-glucuronidase/green
      fluorescent protein reporter lines further uncovered cell- and tissue-specific
      expression patterns, conferring spatiotemporal control of trehalose metabolism.
      Consistently, phenotypic characterization of knockdown and overexpression lines
      of a single TPP, AtTPPG, points to unique properties of individual TPPs in
      Arabidopsis, and underlines the intimate connection between trehalose metabolism
      and abscisic acid signaling.

PMID- 22855941
TI  - Retraction. Push-out bond strengths of two fiber post types bonded with different
      dentin bonding agents.

PMID- 22855942
TI  - Neuroprotective activityof Cymbopogon martinii against cerebral
      ischemia/reperfusion-induced oxidative stress in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon martinii (Roxb.) Watson (Family:
      Graminae), commonly known as Palmarosa, is traditionally prescribed for central
      nervous system (CNS) disorders such as neuralgia, epileptic fits and anorexia.
      Although the plant possesses diverse pharmacological actions, the neuroprotective
      action has got little attention. AIM OF THE STUDY: The present study evaluated
      neuroprotective effect of essential oil of Cymbopogon martinii (EOCM) against
      global cerebral ischemia/reperfusion (I/R)-induced oxidative stress in rats.
      MATERIALS AND METHODS: Global ischemic brain damage was induced by bilateral
      common carotid artery (BCCA) occlusion for 30 min, followed by 60 min reperfusion
      on Wistar albino rats. The biochemical levels of lipid peroxidation (LPO),
      superoxide dismutase (SOD), catalase (CAT), total thiols and glutathione (GSH)
      were estimated and brain coronal sections and histopathological studies were
      performed. RESULTS: BCCA occlusion, followed by reperfusion caused varied
      biochemical/enzymatic alterations viz. increase in LPO and decrease in SOD, CAT,
      total thiols and GSH. The prior treatment of EOCM (50 mg/kg and 100 mg/kg, p.o.
      for 10 days) markedly reversed these changes and restored to normal levels as
      compared to I/R groups. Moreover, brain coronal sections and histopathological
      studies revealed protection against ischemic brain damage in the EOCM-treated
      groups. CONCLUSION: This study, for the first time, shows potent neuroprotective
      effect of EOCM against global cerebral I/R-induced oxidative stress in rats,
      suggesting its therapeutic potential in cerebrovascular diseases (CVD) including
      stroke.

PMID- 22855943
TI  - Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves
      extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Indian medicine, all parts of
      Emblica officinalis Gaertn plant including the fruit, seed, leaves, root, bark
      and flowers are used in various herbal preparations for the treatment of diabetes
      mellitus, chronic diarrhea, anti-inflammatory and antipyretic. AIM OF THE STUDY:
      To evaluate the hypoglycemic and antioxidants effects of the hydro-methanolic
      (20:80) extract of leaves of Emblica officinalis Gaertn. (HMELEO) in
      streptozotocin induced diabetic rats. MATERIAL AND METHODS: The hypoglycemic
      effect was measured by blood glucose and plasma insulin level. The oxidative
      stress was measured in liver and kidney by level of antioxidant markers i.e.
      lipid peroxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH),
      glutathione peroxidase (GPx) and catalase (CAT), and the biochemical parameters,
      i.e. blood serum levels of creatinine, urea, serum glutamic pyruvic transaminases
      (SGPT), serum glutamic oxaloacetic transaminases (SGOT), alkaline phosphatase
      (ALP), total cholesterol and triglyceride levels were the salient features
      observed in diabetic control and treated rats. RESULTS: Oral administration of
      the HMELEO at a concentration of 100, 200, 300 and 400 mg/kg b.w. daily for 45
      days showed a significant (P<0.05) decrease in fasting blood glucose and increase
      insulin level as compared with the diabetic rats. Also it significantly (P<0.05)
      reduced all biochemical parameters (serum creatinine, serum urea, SGOT, SGPT and
      lipid profile). The treatment also resulted in a significant (P<0.05) increase in
      reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, and
      decrease LPO level in the liver and kidney of diabetic rats. CONCLUSION: The
      results clearly suggest that the hydro methanolic extract of leaves of Emblica
      officials Gaertn. treated group may effectively normalize the impaired
      antioxidant status in streptozotocin induced diabetes at dose dependent manner
      than the glibenclamide-treated groups. The extract exerted rapid protective
      effects against lipid peroxidation by scavenging of free radicals and reducing
      the risk of diabetic complications.

PMID- 22855944
TI  - In vitro anti-breast cancer activity of ethanolic extract of Wrightia tomentosa:
      role of pro-apoptotic effects of oleanolic acid and urosolic acid.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Wrightia tomentosa Roem. & Schult. (Apocynaceae)
      is known in the traditional medicine for anti-cancer activity along with other
      broad indications like snake and scorpion bites, renal complications, menstrual
      disorders etc. However, the anti-cancer activity of this plant or its
      constituents has never been studied systematically in any cancer types so far.
      AIM OF THE STUDY: To evaluate the anti-cancer activities of the ethanolic extract
      of W. tomentosa and identified constituent active molecule(s) against breast
      cancer. MATERIAL AND METHODS: Powdered leaves of W. tomentosa were extracted with
      ethanol. The ethanolic extract, subsequent hexane fractions and fraction F-4 of
      W. tomentosa were tested for its anti-proliferative and pro-apoptotic effects in
      breast cancer cells MCF-7 and MDA-MB-231. RESULTS: The ethanolic extract,
      subsequent hexane fractions and fraction F-4 of W. tomentosa inhibited the
      proliferation of human breast cancer cell lines, MCF-7 and MDA-MB-231. The
      fraction F-4 obtained from hexane fraction inhibited proliferation of MCF-7 and
      MDA-MB-231 cells in concentration and time dependent manner with IC50 of 50
      MUg/ml and 30 MUg/ml for 24 h, 28 MUg/ml and 22 MUg/ml for 48 h and 25 MUg/ml and
      20 MUg/ml for 72 h respectively. The fraction F-4 induced G1 cell cycle arrest,
      reactive oxygen species (ROS) generation, loss of mitochondrial membrane
      potential and subsequent apoptosis. Apoptosis is indicated in terms of increased
      Bax/Bcl-2 ratio, enhanced Annexin-V positivity, caspase 8 activation and DNA
      fragmentation. The active molecule isolated from fraction F-4, oleanolic acid and
      urosolic acid inhibited cell proliferation of MCF-7 and MDA-MB-231 cells at IC50
      value of 7.5 MUM and 7.0 MUM respectively, whereas there is devoid of significant
      cell inhibiting activity in non-cancer originated cells, HEK-293. In both MCF-7
      and MDA-MB-231, oleanolic acid and urosolic acid induced cell cycle arrest and
      apoptosis as indicated by significant increase in Annexin-V positive apoptotic
      cell counts. CONCLUSION: Our results suggest that W. tomentosa extracts has
      significant anti-cancer activity against breast cancer cells due to induction of
      apoptosis pathway. Olenolic and urosolic acid are important constituent molecules
      in the extract responsible for anti-cancer activity of W. tomentosa.

PMID- 22855945
TI  - The in vitro antiviral property of Azadirachta indica polysaccharides for
      poliovirus.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Azadirachta indica A. Juss, popularly known as
      neem, has been extensively used in Ayurvedic medicine by Indian population for
      over 2000 years. It is used traditionally for the healing of various diseases.
      Natural products and their derivatives provide an excellent source for new anti
      viral drugs. AIM OF THE STUDY: The present study aims at evaluating the activity
      of two polysaccharides (P1 and P2) isolated from the leaves of Azadirachta indica
      and their chemical sulfated derivatives (P1S and P2S) against poliovirus type 1
      (PV-1). MATERIALS AND METHODS: The cytotoxicity of the compounds was analyzed by
      MTT and the antiviral effect was determined by plaque reduction assay in
      different protocols. RESULTS: The polysaccharides did not show any cytotoxic
      effects on HEp-2 cells at the highest tested concentration (200 MUg/ml) and
      exhibited significant antiviral activity with inhibitory concentrations (IC50) of
      80 MUg/ml, 37.5 MUg/ml, 77.5 MUg/ml, and 12.1 MUg/ml for P1, P1S, P2 and P2S,
      respectively, and the selectivity indexes (SI) ranged from 18 to 131.9. The
      compounds demonstrated better inhibitory effect when added concomitantly with the
      virus infection with a dose-dependent curve inhibition. Lesser effect was
      observed when the compounds were added after viral infection and the least effect
      at pre-treatment. CONCLUSIONS: We suggested that the polysaccharides obtained
      from Azadirachta indica act against PV-1 by inhibiting the initial stage of viral
      replication. Importantly, original polysaccharides showed better virucidal effect
      than their sulfated derivatives at all tested concentrations. This study provides
      a scientific basis for the past and present ethnomedical uses of this plant.

PMID- 22855947
TI  - Dapsone hemolysis.

PMID- 22855946
TI  - Antibiotics attenuate anti-scratching behavioral effect of ginsenoside Re in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Panax ginseng CA Meyer (ginseng) has
      been used for diabetes, cancer, stress and allergic diseases in the traditional
      Chinese medicine. AIM OF THE STUDY: To understand the role of intestinal
      microflora in the pharmacological effect of ginsenoside Re, which is a main
      constituent of ginseng, we investigated its anti-scratching behavioral effect in
      the mice treated with or without antibiotics. MATERIALS AND METHODS: Ginsenoside
      Re was orally administered to the mice treated with antibiotics (cefadroxil,
      oxytetracycline and erythromycin mixture (COE), streptomycin or/and tetracycline)
      and then investigated the relationship between ginsenoside Re-metabolizing beta
      glucosidase and alpha-rhamnosidase activities of intestinal microflora and its
      antiscratching behavioral effect. The anti-scratching behavioral effects of
      ginsenosides were investigated in the increments of 1 h and 6 h after their oral
      administrations. The scratching behavioral frequency was measured for 1 h after
      treatment with histamine. RESULTS: Ginsenoside Re inhibited histamine-induced
      scratching behavior in mice. The anti-scratching behavioral effect of ginsenoside
      Re was more potent 6 h after its oral administration than 1 h after. However, its
      inhibitory effect was significantly attenuated in mice treated with COE, but it
      nearly was not affected in mice treated with streptomycin and/or tetracycline.
      Treatment with COE also significantly lowered fecal ginsenoside Re-metabolizing
      beta-glucosidase and alpha-rhamnosidase activities in mice, as well as fecal
      metabolic activity of ginsenoside Re to ginsenoside Rh1. The anti-scratching
      behavioral effect of ginsenoside Rh1, a metabolite of ginsenoside Re by
      intestinal microflora, was superior to that of ginsenoside Re. Ginsenoside Rh1
      potently inhibited the expression of IL-4 and TNF-alpha, as well as the
      activation of NF-kappaB and c-jun activation in histamine-stimulated scratching
      behavioral mice. CONCLUSION: Ginsenoside Re may be metabolized to ginsenoside Rh1
      by intestinal microflora, which enhances its anti-scratching behavioral effect by
      inhibiting NF-kappaB and c-jun activations.

PMID- 22855948
TI  - Bert Lester Vallee: a lasting legacy.
AB  - The enlightened formation, by Bert and Kuggie Vallee, of a procedure whereby
      senior scientists spend short time of about a month at Harvard, Oxford and other
      institutions, is illustrated by the views and opinions of those selected.

PMID- 22855949
TI  - Zinc in evolution.
AB  - The first part of this paper gives an account of the early work I did with Vallee
      on zinc enzymes. The second part is work and thoughts on zinc biochemistry
      subsequent to this work and following on from it. I shall then put our knowledge
      of zinc biochemistry into the context of the evolution of organisms. The zinc
      proteins are divided into two classes: (1) mainly enzymes often found in the
      early forms of life, prokaryotes, and continued in eukaryotes, showing virtually
      no exchange of zinc; (2) mainly buffers, pumps, chaperones and transcription
      factors all showing faster exchange and largely only found in eukaryotes. The
      complexity of organisms, especially in three steps, prokaryotes, single-cell and
      then multicell eukaryotes, coincides with the two major rises of oxygen. The rise
      of oxygen caused a rise of zinc in the sea as estimated from the analysis of
      sediments. These changes of zinc and other elements with oxygen indicate that
      environmental changes were inevitable. To a considerable extent then the rise of
      organism complexity arose from a need to use and in some cases to avoid the steps
      in element availability. After about 0.5 Ga there has been little change in the
      chemistry of the environment and little in the gross features of the chemistry of
      life notwithstanding the huge increase in diversity. The final paragraph
      acknowledges the inspiration and stimulation of the work of Vallee in the biology
      and biochemistry of zinc.

PMID- 22855950
TI  - Will Rio+20 find a way to more sustainable development?

PMID- 22855951
TI  - Major league nursing.

PMID- 22855952
TI  - Five FDA-approved HPV assays.

PMID- 22855953
TI  - Sales principles to help grow lab revenues--Part II.

PMID- 22855954
TI  - Outright defiance. Some states likely to reject expanding Medicaid.

PMID- 22855955
TI  - Pilot problems. Two programs under heavy scrutiny.

PMID- 22855956
TI  - Largest hospitals. Ranked by total number of staffed beds.

PMID- 22855975
TI  - [Health service research (20). Cultural anthropological approach in the field of
      international health: an intermediary approach at the local and global approaches
      meet].

PMID- 22855976
TI  - Replication study of CYP4F2 association with warfarin  response in an Israeli
      population.

PMID- 22855978
TI  - The ability to identify and discharge the low-risk patient.

PMID- 22855977
TI  - From patient to discoverer--Niels Ryberg Finsen (1860-1904) --the founder of
      phototherapy in dermatology.
AB  - Niels Ryberg Finsen (1860-1904) developed a lamp based on electric carbon arcs
      (later known as the Finsen light) that was used for skin therapy a century ago.
      He became director of the Medical Light Institute in Copenhagen, later the Finsen
      Institute, where he developed this method of treatment. Within a few years, 40
      Finsen Institutes were established in Europe and in the United States of America.
      In 1903, Finsen received the Nobel Prize in Medicine in recognition of his work
      on the treatment of diseases and, in particular, the treatment of lupus vulgaris
      by means of concentrated light rays. Finsen's scientific interests were greatly
      influenced by his health condition. Beginning in 1883, he began to experience
      symptoms of an illness that would be later diagnosed as Niemann-Pick disease. He
      spent the last years of his life confined to a wheelchair. Dermatology reaps the
      benefits of light treatment to this day.

PMID- 22855979
TI  - The goal of the Journal of Invasive Cardiology(r) is to provide state-of-the-art
      information that will support clinicians in the effective management of patients
      with cardiovascular disease.

PMID- 22855980
TI  - ["More, amore" (With love and action) Interview with Zoltan Rihmer by Emoke
      Bagdy].

PMID- 22855981
TI  - Article retraction. Parsian H et al. Relationship between serum hyaluronic acid
      level and stage of liver fibrosis in patients with chronic hepatitis. Biochem Med
      2009;19:154-65.

PMID- 22855982
TI  - Much has changed in cancer clinical trials in the past 10 years.

PMID- 22855983
TI  - Phase 1 clinical trials nursing: determining safety and side effects on the road
      approval.

PMID- 22855984
TI  - What skills and training do phase I clinical research nurses need?

PMID- 22855985
TI  - Studies support value of exercise in patients at different stages of cancer.

PMID- 22855986
TI  - HRSA administrator talks about importance of nurses.

PMID- 22855987
TI  - First trial tests targeted nanoparticles in patients.

PMID- 22855988
TI  - The case of the perplexing platelet product.

PMID- 22855989
TI  - Embrace the future: lead, inspire, and empower.

PMID- 22855990
TI  - [Zoonoses as occupational diseases].
AB  - The article represents materials on risk for animal husbandry workers of being
      infected with Coxiella and Leptospira. The authors describe contemporary
      difficulties in diagnosis and epidemiologic surveillance for these diseases. The
      materials demonstrate that undiagnosed infected (ill) animals on veterinary
      objects, with violated biologic safety rules, could promote contraction of
      zoonotic infection by susceptible subjects (workers engaged into animal husbandry
      and enterprises on animal materials processing). Contemporary laboratory methods
      and professional skills enable opportune and complete diagnosis of infections and
      diseases, with further possibility to apply preventive measures efficiently.

PMID- 22855991
TI  - [The working conditions at animal farm complexes of workers with occupational
      brucellosis].
AB  - According to sanitary-and-hygienic characteristics of working conditions, cards
      certification of working conditions at workplaces, cards of epizootologo
      epidemiological inspection of the zoonotic disease' centres and medical records
      of outpatient working conditions of 134 workers of cattle-breeding complexes of
      Omsk region, professional brucellosis' patients are studied. Harmful factors of
      working conditions' workers of cattle-breeding complexes are the biological
      factor, weight and intensity of labour process (a 3.2-3.3 class), factors
      increasing risk of occurrence professional brucellosis were absence of
      preliminary at receipt for work and/or irregularity periodic physical
      examinations, infringements of sanitary-and-epidemiologic mode, lack of awareness
      of workers about the possibility of brucellosis' contamination in the workplace.

PMID- 22855993
TI  - [Monitoring of functional body status in agricultural machine operators].
AB  - Sanitary and hygienic work conditions of operators of different kinds of combine
      harvesters were evaluated. Pecularities of adaptation of labourers' organism to
      work process were studied. A technique of remote transmission of physiological
      data, obtained in the field conditions to remote laboratory for subsequent expert
      analysis of the results was used.

PMID- 22855992
TI  - [The prevalence of gastroesophageal reflux disease in agricultural workers].
AB  - Among agricultural workers is common gastroesophageal reflux disease. On a
      professional factors affecting agricultural labor (physical activity, weight
      lifting, carrying heavy loads, frequent and/or long slopes). These factors
      contribute to the development of gastroesophageal reflux disease and severe
      course.

PMID- 22855994
TI  - [Cytomorphological assessment of cotton dust effect on the body of experimental
      animals].
AB  - Experimental studies to determine the cytomorphologicalchanges when exposed to
      cotton dust at concentrations 5mg/m3 in 2 months time. Cytomorphological effect
      of the accumulation manifested destructively changed cells in the bronchoalveolar
      lavage, stomach, liver, thyroid, pancreas, spleen, and kidney (females, these
      changes are expressed more).

PMID- 22855996
TI  - [Professional incapability of sailors in Sahalin Region].
AB  - The Studied track record of the professional impracticability 15 115 sailors in
      Sakhalin Region in 2001-2010 years. Factor professional impracticability sailor
      for analysis years realistically increased in 3,3 times with 2,9 +/- 0,9 per
      thousand before 9,5 +/- 2,1 per thousand (p < 0,05), 60,7 % occupy the diseases
      of the cardiovascular system. For reduction professional impracticability sailors
      in Sakhalin Region necessary actions directed on primary and secondary preventive
      maintenance of the cardiovascular pathology.

PMID- 22855995
TI  - [Occupational risk for agricultural workers health, hygienic aspects of its
      assessment and management (literature review)].
AB  - The authors analyzed the facts of contemporary work conditions of agricultural
      production, which are given in non-fiction. The results of analysis showed up
      occupational hazard factors of agricultural workers health. The authors
      determined foreground directions of effective managerial decisions developing,
      concerning its minimization and elimination.

PMID- 22855997
TI  - [To question about integrated prevention of diabetes taking into account the
      technogenic factors of environment (experimental results)].
AB  - Experimental conditions shown that formaldehyde decreased course of diabetes.
      Adding to meal the powder of plant's rhizome Curcuma longa contributes to the
      restoration of the morphological structure of the liver, kidney, the
      normalization of water-salt and carbohydrate metabolism, this can be used in
      programs for integrated prevention of diabetes in areas of technological risk.

PMID- 22855998
TI  - [The preserving-health model of employees of oil and gas industry].
AB  - The state of occupational health problem and occupational rate of accident in
      Russia has been studied. It has been set forward the innovation model of health
      care of employees in oil and gas industry based on integrated approach, which
      combines the medical examination practice, the objective appraisal of workplaces
      on working condition, use of new saving production technologies, providing the
      employees with the means of individual protection, teaching the personnel to
      occupational safety and health culture and the first medical aid. The received
      results approve the efficiency of application of this model.

PMID- 22856000
TI  - How do you stay current?

PMID- 22855999
TI  - [Association of polymorph variants of CYP1A2 and CYP1A1 genes with reproductive
      and thyroid diseases in female workers of petrochemical industry].
AB  - The article presents results obtained in study of relationship between polymorph
      variants of CYP1A1 and CYP1A2 genes with reproductive and thyroid diseases risk
      in female workers of petrochemical industry, when compared with reference group
      females. Variants TD and DD of CYP1A2 gene appeared to be associated with nodes
      formation in uterus and breast in female workers and reference group females.
      Following liability markers are obtained: homozygous in rare allele genotype CC
      of CYP1A1 gene for reproductive and thyroid diseaes (fibrous cystic mastopathy
      and nodular goitre), heterozygous genotype AG of CYP1A1 gene in uterine myoma and
      fibrous cystic mastopathy, homozygous in deleted T genotype of CYP1A2 gene in
      autoimmune thyroiditis. Occupational hazards and long length of service at
      hazardous industries increase effects of rare alleles of the genes studied.

PMID- 22856001
TI  - What are the benefits of a professional corporation?

PMID- 22856002
TI  - Mandating out-of-office staff training may cost you.

PMID- 22856003
TI  - The ADA's statement on dental patient rights and responsibilities.

PMID- 22856004
TI  - Coverage for core buildup procedures.

PMID- 22856005
TI  - The times, they are a-changin'.

PMID- 22856006
TI  - Diagnostic dilemma: the enigma of an oral burning sensation.

PMID- 22856007
TI  - Management of burning mouth syndrome.
AB  - Burning mouth syndrome is a challenging condition in terms of both diagnosis and
      management. These challenges lead to frustration for patients and difficulties
      for dental practitioners. Unfortunately, delays are common between initial
      presentation and definitive diagnosis, and also between diagnosis and appropriate
      management. Furthermore, interventions are often undertaken without a working
      diagnosis, knowledge of the underlying condition or knowledge of best management
      strategies for this form of chronic orofacial pain. This article discusses
      potential reasons for diagnostic delays. It also presents current strategies for
      managing burning mouth syndrome, to assist the dental practitioner in making
      prudent therapeutic

PMID- 22856008
TI  - The Smiles are Everywhere dental program: a dental home in a Winnebago bus.

PMID- 22856009
TI  - Where is it?

PMID- 22856010
TI  - Bowen-Conradi: a common Hutterite condition that mimics trisomy 18.
AB  - Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive condition having
      significant clinical overlap with trisomy 18. Though rare in the general
      population, it is quite common in the Hutterites of the United States and Canada.
      The carrier frequency in the Hutterite population is estimated to be one in 10,
      making BCS one of the most commonly inherited genetic diseases in any human group
      studied to date. We describe two infant patients who were initially thought to
      have trisomy 18, but for whom chromosome studies were normal. Additionally, we
      briefly review the historical background of the Anabaptist Hutterite populations
      in South Dakota, compare the clinical findings in BCS and trisomy 18 and discuss
      the importance of genetic counseling for couples of Hutterite descent.

PMID- 22856011
TI  - Vitamin D status in eastern South Dakota.
AB  - BACKGROUND: Vitamin D deficiency is prevalent in the general U.S. population. To
      date, although there are a number of case reports, no studies of the prevalence
      of vitamin D deficiency in the general population of the upper Midwest have been
      reported. The present study was undertaken to define the vitamin D status in
      three groups: healthy working adults, pregnant women and nursing home residents.
      METHODS: A prospective evaluation of serum vitamin D levels. RESULTS: Seventy
      five percent of healthy working adults, 63 percent of nursing home residents and
      83 percent of maternity patients had serum calcidiol levels below 32 ng/mL. Mean
      levels were 26.4 ng/mL, 28.8 ng/mL, and 20.7 ng/mL, respectively. CONCLUSION:
      Hypovitaminosis D is highly endemic in this region's population; routine
      supplementation and/or empiric replacement therapy should be considered,
      especially as a part of routine prenatal care.

PMID- 22856012
TI  - New sedation practices in the adult intensive care unit: analgosedation.

PMID- 22856013
TI  - Quality focus: update on care transitions.

PMID- 22856014
TI  - DAKOTACARE update: what you don't know can hurt you.

PMID- 22856015
TI  - A doctor's story.

PMID- 22856016
TI  - Comprehensive cancer control--impacting every physician.

PMID- 22856017
TI  - Connecticut Cancer Partnership: the development of a statewide comprehensive
      control program.

PMID- 22856018
TI  - Connecticut's Cancer Control Program.

PMID- 22856020
TI  - Cancer control not cancer care: a public health perspective.

PMID- 22856019
TI  - The burden of cancer in Connecticut.
AB  - Considerable progress in cancer prevention, early detection and treatment has led
      to a reduction in the incidence and mortality of this disease, and resulted in
      significant improvements in cancer survival. Despite these advances, certain
      populations in Connecticut continue to suffer disparately from this frequently
      debilitating disease. In this article, we use data from the Connecticut Tumor
      Registry to examine trends in the four most commonly diagnosed cancers (breast,
      prostate, lung and colorectal) that collectively account for more than 50% of
      cancers diagnosed annually in Connecticut. We report on time trends and compare
      incidence and mortality rates, stage at diagnosis, survival and screening rates,
      giving insight into opportunities to improve health and reduce disparities in
      residents of the state.

PMID- 22856021
TI  - Results of nine Connecticut Cancer Partnership implementation projects.
AB  - The Connecticut Cancer Partnership (Partnership), through funds from the
      Connecticut legislature, the AttorneyGeneral Fund and some limited federal
      funding, has spearheaded the implementation of a series of projects by
      Connecticut institutions and State of Connecticut departments. Among them are
      projects in prevention, detection, treatment, survivorship and end-of-life care,
      along with programs that target ethnic and uninsured populations. This article
      highlights funding sources, procedures for choosing projects and summaries for
      nine completed projects of interest to practicing physicians. It also includes a
      listing of additional projects currently underway. The use of shared funding
      among the State's partners highlights the energy of the Partnership in carrying
      out the common vision embodied in the Connecticut Cancer Plan.

PMID- 22856022
TI  - Scientific horizons in cancer control: genomes, informatics and personalized
      medicine.
AB  - The goals of cancer control are to reduce cancer risk, detect cancers earlier,
      improve treatments and enhance the health of cancer survivors. Personalized
      medicine aims to customize health care by tailoring care to the individual
      patient using genetic and other information. This review considers the
      traditional strengths of Connecticut's cancer control program as well as trends
      in emerging science, primarily under development through the auspices of the
      National Cancer Institute's Division of Cancer Control and Population Sciences.
      It focuses on resources for cancer control offered by the Connecticut Tumor
      Registry in addition to opportunities for improving cancer control through
      developments in informatics and cancer genomics. It provides an overview of the
      use of informatic tools, electronic health records, health information exchange,
      integration of genotyping into risk models, and genomic analyses of clinical
      tumor specimens, demonstrating how the common theme in these advances will lead
      toward more personalized cancer control.

PMID- 22856023
TI  - A medical home for a breast cancer survivor.

PMID- 22856024
TI  - The treatment of tumors of the mammary gland. 1912.

PMID- 22856025
TI  - Cancer control in Connecticut.

PMID- 22856026
TI  - Defending our interests--our collective responsibility.

PMID- 22856027
TI  - Flexner revisited.

PMID- 22856028
TI  - The end of the world ... or not.

PMID- 22856030
TI  - Put down the cake.

PMID- 22856029
TI  - Future ramifications of zirconia crowns.

PMID- 22856031
TI  - Dentures effectively disinfected in microwave.

PMID- 22856033
TI  - Esthetic transformation of a failed implant reconstruction to fixed-supported
      prosthesis: a case report.
AB  - This article describes a clinical situation where an ill-fitting prosthesis
      supported by malpositioned dental implants was esthetically transformed to fixed
      definitive restorations. Provisional restorations were used as a blueprint for
      fabrication of definitive restorations.

PMID- 22856032
TI  - The importance of the optical properties in dental silica-based ceramics.
AB  - To make esthetic rehabilitation similar to the natural teeth, all-ceramic
      restorations must have equal optical properties to the natural teeth in terms of
      color, translucency, fluorescence, and opalescence. Furthermore, a correct
      communication process with the laboratory is the key to success and
      biointegration with the ceramic indirect restoration and the teeth.

PMID- 22856034
TI  - Ultimate ceramic veneer: a laboratory-guided preparation technique for minimally
      invasive laminate veneers.
AB  - Clinical success of ceramic laminate veneers depends on material selection,
      bonding procedures, controlled laboratory steps, and enamel preservation. Enamel
      preservation is the most critical because excessive tooth preparation can expose
      dentin reducing bond strength, which is a factor that can cause a decrease in
      long-term clinical success. The proposed technique based on carefully treatment
      planning developed between clinician and dental technician helps to maximize
      enamel preservation, which is an important element for clinical success.

PMID- 22856035
TI  - Implant-supported full-mouth reconstruction Malo Implant Bridge.
AB  - This article describes the clinical techniques and laboratory procedures for
      fabricating a predictable Malo Implant Bridge involving application of an
      occlusal screw-retained implant superstructure on the basis of the All-on-4
      concept. The Malo Implant Bridge features a removable occlusal screw-retained
      superstructure; fabrication of the framework with a computer-aided
      design/computer-aided manufacturing system allowing accurate adaptation; and use
      of the final tooth position model with guide temporary crowns allowing easy
      porcelain build-up and satisfying the patient's esthetic concerns.

PMID- 22856037
TI  - Celebreteeth for sale.

PMID- 22856036
TI  - Esthetic considerations for the treatment of the edentulous maxilla based on
      current informatic alternatives: a case report.
AB  - This report presents a protocol used to transfer the virtual treatment plan data
      to the surgical and prosthetic reality and its clinical application, bone site
      augmentation with computer-custom milled bovine bone graft blocks to their ideal
      architecture form, implant insertion based on image-guided stent fabrication, and
      the restorative manufacturing process through computed tomography-based software
      programs and navigation systems and the computer-aided design and manufacturing
      techniques for the treatment of the edentulous maxilla.

PMID- 22856038
TI  - U.S. Supreme Court takes up ACA.

PMID- 22856039
TI  - Nurses leading through innovation.

PMID- 22856040
TI  - Professional service organizations.

PMID- 22856041
TI  - Re: Board service.

PMID- 22856042
TI  - Re: assessinq competence to practice.

PMID- 22856043
TI  - Re: assessinq competence to practice.

PMID- 22856044
TI  - Re: assessing competence to practice.

PMID- 22856045
TI  - Re: assessing competence to practice.

PMID- 22856046
TI  - Re: assessing competence to practice.

PMID- 22856047
TI  - Re: assessing competence to practice.

PMID- 22856048
TI  - Increasing productivity in dental practice: the role of ancillary personnel.
AB  - Dentistry has achieved substantial improvements in productivity which have the
      effect of making more care available at reasonable cost. Data are presented
      documenting trends in productivity. These are analyzed with respect to number of
      dentists, hours worked by dentists, and the use of ancillary personal in dental
      offices. There is strong evidence linking increased productivity to the use of
      ancillary personnel. The history of creation, recognition, and integration of
      ancillary personnel into dental practice is also presented.

PMID- 22856049
TI  - Readiness requires a team.
AB  - The mission of the Navy Dental Corps is to ensure combat readiness. In addition
      to commissioned dental officers, oral health care is provided by auxiliaries such
      as dental hospital corpsmen, the traditional dental hygienist, and the
      independent duty corpsman.

PMID- 22856050
TI  - The human capital crisis in orthodontics.
AB  - The economics of dental practice are changing. The author reflects on the loss of
      a long-term, highly effective, and dedicated assistant in an orthodontic
      practice. Changes in technology, numbers of dentists, expected benefit levels,
      and a competitive workplace environment are combining to put pressures on the
      traditional model of oral health care. Whatever the solution turns out to be, the
      profession should take the lead in actively developing alternatives, and these
      will necessarily involve development of human capital in the dental practice.

PMID- 22856051
TI  - ThE Alaska Native Tribal Health System Dental Health Aide Therapist as a dentist
      centric model.
AB  - Differences in disease patterns and living circumstances should play no role in
      the quality of oral health care or in dentists' role in directing this care. Such
      differences, however, very likely suggest that the delivery model that works in
      many circumstances may not be best in all. The Alaska Tribal Health System Dental
      Health Aide Therapist (DHAT) model is one alternative whose potential is being
      evaluated. These teams are managed by dentists and have several features in
      common with general practice residency training programs. Alaska dentists
      supervising DHATs customize their practice protocols based on the skills of the
      therapists and the needs of the communities served. The emphasis of therapists is
      on prevention and basic oral health services, leaving the dentists to focus on
      higher level treatment that better uses the skills for which they have been
      trained. The characteristics of effective dentist team managers and the economic
      and social realities of this program are discussed.

PMID- 22856052
TI  - Looking at the past to see the future: the role of the dental hygienist in
      collaborating with dentists to expand and improve oral health care.
AB  - As dental hygiene approaches its 100th anniversary in 2013, it is clear that the
      profession has evolved far beyond the initial vision of Dr. Alfred Fones. Much of
      this evolution has been driven by changing oral health needs of the public as
      well as the way dentists practice, based on innovations in dentistry, to
      concentrate on more advanced procedures and delegate other duties to the dental
      hygienist. By and large, these changes have been achieved by dentists, dental
      hygienists, and other team members working together. We have an opportunity to
      overcome initial resistance and, based upon evidence of successful outcomes,
      further extend the reach of the dental team for the benefit of patients,
      especially the most vulnerable among them.

PMID- 22856053
TI  - The person who wears the white coat.
AB  - Legal practice, charity care, and professionalism are the outward signs of dental
      competence, symbolized by the white coat. Ethics, the transformation of
      character, is a reflection of the person wearing the white coat. Patients and
      others assume the first three from the title "doctor." What they want to know is
      what kind of person is wearing the white coat.

PMID- 22856054
TI  - Schadenfreude: an all too common affliction.
AB  - The ADA Code of Professional Conduct requires that care be taken that criticism
      of colleagues' work is justifiable. Several cases are presented where this
      standard appeared not to have been met, and the consequences were dire for all
      involved. Sometimes unjustified criticism can be as inadvertent as ambiguous body
      language; sometimes it is possible to interpret unjustified criticism as being
      driven by envy or by what the Germans call schadenfreude--satisfaction at others'
      misfortunes.

PMID- 22856055
TI  - Energy.
AB  - Energy is the capacity to do the things we are capable of and desire to
      accomplish. Most often this is thought of in terms of PEP--personal energy
      potential--a reservoir of individual vivacity and zest for work. Like a battery,
      energy can be conceived of as a resource that is alternatively used and
      replenished. Transitions between activities, variety of tasks, and choices of
      what to spend energy on are part of energy management. Energy capacity can be
      thought of at four levels: (a) so little that harm is caused and extraordinary
      steps are needed for recovery, (b) a deficit that slightly impairs performance
      but will recover naturally, (c) the typical range of functioning, and (d) a
      surplus that may or may not be useful and requires continual investment to
      maintain. "Flow" is the experience of optimal energy use when challenges balance
      capacity as a result of imposing order on our environment. There are other energy
      resources in addition to personal vim. Effective work design reduces demands on
      energy. Money, office design, and knowledge are excellent substitutes for
      personal energy.

PMID- 22856056
TI  - Educating for partnering.

PMID- 22856057
TI  - Partnership nursing: recovering lost threads of the nursing story.
AB  - Nursing has been challenged to claim full partnership with other health care
      providers. To reach this goal nurse educators must ensure that curriculum and
      textbooks provide appropriate content on the nature and use of power, how to
      collaborate, and how to develop partnerships.

PMID- 22856058
TI  - Preparing nursing students to be effective health team partners through
      interprofessional education.
AB  - This article will provide an overview of recent significant activities related to
      interprofessional education to promote care quality through teamwork and
      collaboration, followed by a discussion of what nursing schools can do to develop
      the knowledge, skills, attitudes, and values to enhance health care team
      performance and care outcomes.

PMID- 22856059
TI  - Foundations of interprofessional communication and collaboration.
AB  - Communication and collaboration skills are important now among health
      professionals and are likely to become absolutely vital in the future. Health
      care team efficiency will be the hallmark of clinical and financial success as
      care delivery systems continue to evolve. Teaching these skills to beginning
      health professions students, with reinforcement throughout their education, is an
      exciting development in academia.

PMID- 22856060
TI  - Nurse #65X89: the emerging story from an emancipatory study of nursing practice.
AB  - This article provides a creative account of contemporary nursing practice
      challenges by using a unitary appreciative inquiry process to create a metastory.
      A brief review of the Nurse Manifest Project is followed by the story "Nurse
      #65X89." Nurses are encouraged to explore their own emerging stories and to
      define avenues for action, emancipation, and change for the profession.

PMID- 22856061
TI  - Grade inflation: a problem in nursing?
AB  - This article examines grade inflation in higher education and in nursing
      education. The factors related to grade inflation and consequences of grade
      inflation are explored. Actions that address grade inflation and recommendations
      for future research in nursing education are provided.

PMID- 22856062
TI  - Nursing care plans versus concept maps in the enhancement of critical thinking
      skills in nursing students enrolled in a baccalaureate nursing program.
AB  - Appropriate and effective critical thinking and problem solving is necessary for
      all nurses in order to make complex decisions that improve patient outcomes,
      safety, and quality of nursing care. With the current emphasis on quality
      improvement, critical thinking ability is a noteworthy concern within the nursing
      profession. An in-depth review of literature related to critical thinking was
      performed. The use of nursing care plans and concept mapping to improve critical
      thinking skills was among the recommendations identified. This study compares the
      use of nursing care plans and concept mapping as a teaching strategy for the
      enhancement of critical thinking skills in baccalaureate level nursing students.
      The California Critical Thinking Skills Test was used as a method of comparison
      and evaluation. Results indicate that concept mapping enhances critical thinking
      skills in baccalaureate nursing students.

PMID- 22856063
TI  - Fourth stage of labor and midwifery.

PMID- 22856064
TI  - Teso Safe Motherhood Project and Soroti Regional Referral Hospital.

PMID- 22856065
TI  - The fourth stage: sharing the Asian way.

PMID- 22856066
TI  - First hours after birth: family integration and mutual regulation.

PMID- 22856067
TI  - Childbirth from a bacteriological perspective.

PMID- 22856068
TI  - Building my nest.

PMID- 22856069
TI  - No midwife left behind.

PMID- 22856070
TI  - Evidence-based midwifery: the case against newborn suctioning.

PMID- 22856071
TI  - Let time stand still: bonding with your baby.

PMID- 22856072
TI  - The fourth trimester and the calming reflex: novel ideas for nurturing young
      infants.

PMID- 22856073
TI  - I am not God.

PMID- 22856074
TI  - Stanislawa Leszczynska: the midwife of Auschwitz.

PMID- 22856075
TI  - Postpartum emotions.

PMID- 22856076
TI  - A new understanding: relating to c-section trauma via abdominal hernia surgery.

PMID- 22856077
TI  - All that matters is a healthy husband.

PMID- 22856078
TI  - Violence, the human experience and midwifery.
AB  - Sarah Proechel, Midwife International clinical director, reflects on the state of
      violence in the world today including its presence in birth and explores its
      roots as deeply embedded in the human experiences of shame and vulnerability. She
      offers the role of the midwife as an opportunity to transform violence at the
      source, holding the space for a more peaceful world to be born.

PMID- 22856079
TI  - Neonatal resuscitation with intact umbilical cord.
AB  - This paper investigates neonatal resuscitation with the umbilical cord intact.
      Research confirms numerous immediate and long-term benefits to leaving the cord
      intact while performing neonatal resuscitation in both term and preterm neonates,
      while doing no harm. Current neonatal resuscitation guidelines from around the
      world are discussed with respect to the cord. Methods for incorporating an intact
      cord into standard resuscitation procedures are explored.

PMID- 22856080
TI  - Prodromal labor: Terra's birth story.

PMID- 22856081
TI  - Prenatal ultrasound does not improve perinatal outcomes.
AB  - Based on accurate randomized controlled studies, the correct evidence-based
      recommendation would be for women not to undergo prenatal ultrasound except to
      assist with turning a breech baby to head down, evaluating ectopic pregnancy and
      directing the needle during amniocentesis and fetal blood transfusions. First and
      second trimester organ scans, biophysical profile (BPP), amniotic fluid index
      (AFI), placental grading 0-III and Doppler umbilical, uterine and fetal artery
      velocity testing have been tested in randomized controlled studies on tens of
      thousands of women. They are used to attempt to predict suspected fetal growth
      restriction (FGR or IUGR), suspected placental insufficiency and suspected
      postdate pregnancy. They are unable to predict those with sufficient accuracy to
      direct management that will reduce the number of stillbirths or improve perinatal
      mortality rates and in most settings result in increased cesarean rates as a
      result of failed induction.

PMID- 22856082
TI  - Social media and midwives: what is appropriate?

PMID- 22856083
TI  - A triumphant homebirth story.

PMID- 22856084
TI  - Compound presentation: in HBAC triumph!

PMID- 22856085
TI  - Building communities of lactation support.

PMID- 22856086
TI  - Pokot tribe.

PMID- 22856087
TI  - Kraamverzorgsters: postpartum aid in The Netherlands.

PMID- 22856088
TI  - Homebirth in Puerto Rico: a little-known choice.

PMID- 22856089
TI  - Birth in Israel.

PMID- 22856090
TI  - "Care will suffer if staff satisfaction is neglected".

PMID- 22856091
TI  - Cuts fuel fears over future care.

PMID- 22856093
TI  - "You don't need to be Einstein to see the dangers of overwork".

PMID- 22856092
TI  - "Get involved with the forum's work to reduce care variations".

PMID- 22856094
TI  - "Lack of community support puts strain on family carers".

PMID- 22856095
TI  - Exploring the professional identity of health visitors.
AB  - Health visiting is a complex, diverse and varied role. This article reviews the
      development of the role and how this has affected health visitors' professional
      identity.

PMID- 22856096
TI  - Feeding hospital patients: a multiprofessional approach.
AB  - Nurses have a key role in ensuring that inpatients receive adequate nutrition and
      hydration. This article gives practical advice on helping patients during
      mealtimes.

PMID- 22856097
TI  - Raising nurses' awareness of nutritional supplements.
AB  - Hospital patients are at increased risk of malnutrition and may need oral
      nutritional supplements. This article describes the development of a poster to
      raise nurses' awareness of the importance of chilling supplements to encourage
      patients to take them and find out their preferred flavours.

PMID- 22856098
TI  - A governance framework for advanced nursing.
AB  - This second in a three-part series outlines the introduction of a governance
      framework for advanced nursing practice. Part 1 explored the history of the
      evolution of advanced practice, while part 3, to be published next week, will
      discuss the future of advanced practice and how it may shape the career structure
      of nursing.

PMID- 22856100
TI  - How job sharing helps employers.

PMID- 22856099
TI  - A person-friendly ward.

PMID- 22856101
TI  - Stop all of that unnecessary testing! (Oh, and by the way, can you also get the
      patients to care about their health?).

PMID- 22856102
TI  - Cardiopulmonary resuscitation inpatient outcomes in cancer patients in a large
      community hospital.
AB  - BACKGROUND: Patients and clinicians have unrealistic expectations when it comes
      to cardiopulmonary resuscitation (CPR). Only a small percentage of patients
      survive a cardiopulmonary arrest and those that do live, still have a high
      likelihood of dying in the hospital. The quality of life for those patients who
      do survive to discharge is often severely diminished. For cancer patients, the
      statistics may be even worse. OBJECTIVE: To determine and compare the rate of
      survival of adult patients, with and without malignancy, after undergoing in
      hospital cardiopulmonary resuscitation. The purpose of obtaining this data is to
      provide clinicians with tools to effectively and honestly discuss expectations
      concerning end of life issues with cancer patients. METHODS: A retrospective
      medical record review from a single large community hospital involved 154 adult
      patients (> or = 18 years of age) who had undergone an in-patient cardiopulmonary
      arrest from October 1999 to October 2011 on a combined medical oncology/medical
      nursing unit. The patients were divided into two groups: those with a known
      active malignancy and those without cancer. The groups were further categorized
      by various characteristics. The end points included the number of survivors at
      day 0 and day 30 after CPR. RESULTS: There were a total of 94 cancer patients and
      60 non-cancer patients. The cancer patients were subdivided into those with solid
      tumors (63 patients) versus those with hematological malignancy (31 patients).
      The solid tumor group was further divided into localized (23 patients) and
      metastatic (40 patients) disease. The cancer patients were also divided by age,
      those 65 and older (37 patients) and those less than 65 years of age (57
      patients). The non-cancer group was similarly divided into 65 and older (38
      patients) and younger than 65 (22 patients). In total 16 percent of all cancer
      patients were alive at day 30 compared to 23 percent of non-cancer patients (p =
      0.167). With respect to solid vs. hematologic tumors, both had a survival rate of
      16 percent at 30 days. When comparing age differences, the younger non-cancer
      patients had better outcomes (27 percent survival rate) compared with younger
      oncology patients (18 percent). There was not a significant difference in
      survival between the older patients in either group. CONCLUSION: Overall the rate
      of survival of cancer patients in a community hospital after undergoing CPR is
      similar to what is described in the recent literature. The prognosis remains poor
      for cancer patients undergoing CPR. Therefore, clinicians should and are now
      mandated by law (in certain states) to engage in honest discussions using data
      concerning end of life care and expectations.

PMID- 22856103
TI  - A controversial viewpoint on aging and medical technology.

PMID- 22856104
TI  - CMS final rule requires NPI submission for Medicare and Medicaid provider
      enrollments and orders.
AB  - Despite the recent debate in the U.S. Supreme Court regarding the
      constitutionality of the health care reform act, CMS published a final rule
      related to several provisions from the Affordable Care Act (the Act).

PMID- 22856105
TI  - Nurturing potential. Being a mentor is a powerful thing.

PMID- 22856106
TI  - Reaching the top. Reflections on the importance of education in the dental field.

PMID- 22856107
TI  - "We don't get along, but the patient doesn't know!"--resolving conflict in the
      dental practice.

PMID- 22856108
TI  - Taking charge of temporization. Tips on proper temporization techniques.

PMID- 22856109
TI  - Progress in HIV care.

PMID- 22856110
TI  - Convenient care's second spring.

PMID- 22856111
TI  - Primary care and population health.

PMID- 22856112
TI  - The top 5 faux pas committed by job seekers.

PMID- 22856113
TI  - HIV/AIDS in 2012: key treatment issues.

PMID- 22856114
TI  - Diagnosing peanut allergy: molecular allergy testing provides a more complete
      picture.

PMID- 22856115
TI  - Are you at risk for stroke? Know the warning signs and risks.

PMID- 22856116
TI  - Rosacea overview: patients require attention to skin care and self-esteem.

PMID- 22856117
TI  - Transition: a part of life.

PMID- 22856118
TI  - Preparing to lead... the journey continues for NCNA Leadership Academy Class.

PMID- 22856119
TI  - What will happen to the nursing workforce in the years ahead?

PMID- 22856120
TI  - [80-th anniversary of Moscow Neurosurgical Institute: history and achievements].

PMID- 22856121
TI  - [Endoscopic endonasal surgery of pituitary adenomas (experience of 1700
      operations)].
AB  - The current paper analyses results of endoscopic endonasal surgical treatment of
      1700 patients with pituitary adenomas in Burdenko Neurosurgical Institute during
      recent 7 years. We assessed the following parameters: dynamics of basic syndromes
      (neuroophthalmological, neurological and endocrinological symptoms), degree of
      resection, frequency and types of postoperative complications, postoperative
      mortality, recurrence rate etc. The obtained data were compared with results of
      microsurgical transnasal operations which were formerly performed in our
      department, as well as with results of leading endoscopic neurosurgeons of the
      world. In majority of parameters our results are on the same level as the data of
      most prominent endoscopic neurosurgeons of the world and are significantly better
      that in the group of patients operated using a microscope.

PMID- 22856122
TI  - [Microsurgical treatment of cerebral arteriovenous malformations in Burdenko
      Neurosurgical Institute (recent experience)].
AB  - Recently the number of AVM resections in Burdenko Neurosurgical Institute has
      been increased dramatically. Aim of this study was to assess the results of open
      surgery in our clinic in modern neurosurgical era. Consecutive series if 160
      patients with AVM treated using microsurgical technique since 2009 till 2011 was
      analyzed. Spetzler-Martin score distribution was: grade I--29 (18.1%) cases,
      grade II--84 (52.5%), grade III--38 (23.8%), grade IV--9 (5.6%). Patients with
      grade V AVMs were not operated. Treatment options included: AVM resection in 143
      (89.4%) cases, embolization followed by resection in 15 (9.3%) and clipping of
      afferents in 2 (1.3%). Glasgow outcome scale score distribution was the
      following: V (good recovery)--70 (43.7%), IV (moderate disability)--71 (44.4%),
      III (severe disability)--16 (10%), II (vegetative state)--1 (0.6%) and I (death)-
      2 (1.3%). Microsurgery remains the primary option for radical treatment of
      cerebral AVMs. Careful selection of patients and planning of surgery are crucial
      for good outcomes.

PMID- 22856123
TI  - [Substantiation of differentiated management of patients with multiple cerebral
      aneurysms].
AB  - The study was performed to substantiate optimal tactics of management of patients
      with multiple cerebral aneurysms based on analysis of surgical results. This
      study included 233 (20%) patients with multiple cerebral aneurysms who were
      treated in Burdenko Neurosurgical Institute since 1995 till 2007. We analyzed
      results of single-stage (microsurgical technique) and multistage (microsurgical
      technique and step-by-step application of endovascular and microsurgical
      techniques) approaches. The following factors were investigated: severity of
      subarachnoid hemorrhage (Hunt-Hess scale), localization of aneurysms in different
      arterial systems, quantity and size of aneurysms.. Postoperative mortality was
      4.7%. Poor outcomes were observed in 37 (16%) patients. In multi-stage surgical
      treatment the number of totally occluded aneurysms was significantly higher (92%
      vs. 79%, p < 0.05) as the number of palliative operations and untreated aneurysms
      was lower (5.8% vs. 16%, p < 0.05). The best technical and clinical results were
      obtained in the group of patients who were treated using step-by-step application
      of endovascular and microsurgical techniques. Despite coexistence of aneurysms of
      both carotid systems with vertebrobasilar aneurysms in 15% of this group, poor
      outcomes were not observed and total occlusion of aneurysms was performed in
      91.4% of cases. Obtained technical and clinical results of treatment of multiple
      aneurysms prove that multi-stage surgical management is the therapy of choice in
      surgery of multiple aneurysms. Our data demonstrate high effectiveness of
      multimodal approach with integration of endovascular and microsurgical methods.
      Combination of both techniques is preferential in coexistence of aneurysms of
      carotid and vertebrobasilar systems.

PMID- 22856124
TI  - [Arteriovenous malformations of the Galen vein: results of treatment].
AB  - We performed retrospective and prospective analysis of surgical treatment of
      arteriovenous malformations of vein of Galen. Since 1987 till 2009 90 patients
      were operated in Burdenko Neurosurgical Institute. Age varied between 1 month and
      38 years, 69 patients were children below 10. The paper describes main techniques
      for early diagnosis of the disease, its manifestation depending on age and type
      of malformation, treatment modalities, early postoperative and follow-up results.
      Endovascular treatment was applied in 75 (83.3%) patients. Complications with
      persistent neurological deficit after endovascular occlusion were observed in 10
      (16%) patients, 2 patients died shortly after surgery. CONCLUSION: endovascular
      surgery is the treatment of choice in arteriovenous malformations of vein of
      Galen; optimal age for endovascular procedure is 4-5 months; observation in
      asymptomatic course is ineffective.

PMID- 22856126
TI  - [Decompressive hemicraniectomy in extensive ischemic middle cerebral artery
      stroke].

PMID- 22856125
TI  - [Analysis of radiological criteria correlation and clinical manifestation of
      central lumbosacral spinal stenosis].
AB  - OBJECTIVE: to assess the correlation analysis of radiologic criteria referred to
      central degenerative spinal stenosis and intensity of clinical manifestation.
      MATERIALS AND METHODS: a retrospective cohort data were collected from 2010 till
      2011, 27 patients who underwent surgical treatment of central spinal stenosis in
      Burdenko Neurosurgical Institute. 16 male and 11 female patients were included in
      the present study. Mean age of the patients at the time of surgery was 57.9
      years. All patients had spinal canal decompression and transpedicular or oblique
      transcorporal fusion. Stabilization included different types of pedicle screws,
      including transcutaneous stabilization systems. Interbody fusion was achieved by
      posterolateral transforaminal approach (TLIF --transforaminal lumbar interbody
      fusion). 13 cases included combination of interbody fusion and guided oblique
      lumbar interbody fusion "GO-LIF", which could not be managed without robotic
      assistance. All patients underwent full preoperative examination. MR image
      evaluation included: antero-posterior diameter of the spinal canal (mm),
      interfacet interval (mm), and cross-section area of the spinal canal (mm2).
      Patients were evaluated by outcome analysis scales: Degenerative Disease
      Intensity Level (DDIL) and Swiss Spinal Stenosis Score (Zurich Claudication
      Questionnaire, Brigham spinal stenosis questionnaire). Surgical outcomes were
      evaluated according to modified classes of Kawabata et al. RESULTS AND
      DISCUSSION: analysis of our patients group demonstrated absence of correlation
      between intensity level of degenerative central spinal stenosis based on
      neurovisualization methods and intensity of its clinical manifestation. Pearson's
      coefficient of correlation and Spearmen rank correlation for variable which
      evaluates clinical signs (DDIL in %) and neurovisualization data (antero
      posterior diameter of the spinal canal (mm), interfacet interval (mm), and cross
      section area of the spinal canal (mm2)) are not significant to zero (p > 0.2).

PMID- 22856128
TI  - [Brain tumors in infants].

PMID- 22856127
TI  - [Cervical spondylogenic myelopathy: diagnostics, treatment, prognosis].
AB  - The authors present a review of literature focusing on state-of-art of surgical
      management of cervical spondylogenic myelopathy (CSM). Pathophysiology of CSM,
      evaluation and differential diagnosis are also described. Special attention is
      given to the value of neurophysiological aspects in pre- and postoperative
      examination.

PMID- 22856130
TI  - [Computer classification models on the relationship between chemical structures
      of compounds and drugs with their blood brain barrier penetration].
AB  - Ability of drugs to cross blood-brain barrier (BBB) (BBB+ for BBB-penetrating and
      BBB- for non-penetrating compounds) is one of the most important properties of
      chemicals acting on the central nervous system (CNS). This work presents the
      results of modelling of the relationship between chemicals structure and BBB
      crossing ability. The data set included 1513 compounds BBB+/- (1276 BBB+ and 237
      BBB-). Computer modelling of structure-activity relationship was realized by two
      directions: using the "read-across" method and linear discriminant analysis (LDA)
      based on physico-chemical descriptors. It was found that a sum of donor-acceptor
      factors is the principal parameter, which define BBB penetration.

PMID- 22856129
TI  - [Clinical and prognostic value of inflammatory genetic markers in traumatic brain
      injury].
AB  - The paper analyses the published data about association of polymorphic gene
      markers of different bioactive agents (interleukins, angiotensin convertase,
      catechol-O-methyltransferase, dopamine receptors etc.) with traumatic brain
      injury. Analysis of the entire pool of data concerning clinical and experimental
      studies of association of different polymorphic markers of candidate genes with
      outcome of traumatic brain injury allows to conclude that IL 1alpha and IL 1beta,
      IL 6, catechol-O-methyltransferase, angiotensin convertase, D2 dopamine receptors
      in fact play important role in neuroinflammatory response to injury and recovery
      of the brain ant its functions. Moreover presence or absence of certain
      polymorphic gene markers differentially influence separate pathogenetic
      mechanisms of brain injury (e.g., severity of brain edema, cerebral blood flow,
      cognitive functions). Consequently each of the investigated genes contributes in
      outcome after traumatic brain injury.

PMID- 22856131
TI  - [Mechanisms of anti-cancer effects of plant polyphenols. II. Suppression on tumor
      growth].
AB  - Mechanisms of suppression of carcinogenesis promotion/progression by plant
      polyphenols have been considered. They can decrease cyclins and cycline dependent
      kinases and activate inhibitor proteins in tumor cells that results in cell cycle
      arrest. Plant polyphenols can induce apoptosis by modulating anti/proapoptotic
      proteins and also can inhibit tumor metastasis and angiogenesis. Polyphenols act
      through the regulation of cell signal transduction and gene expression.

PMID- 22856132
TI  - [Binase penetration into alveolar epithelial cells does not induce cell death].
AB  - Microbial ribonucleases possess a broad spectra of biological activities,
      demonstrating stimulating properties at low concentrations and cytotoxicity and
      genotoxicity at high concentrations. The mechanisms of their penetration into the
      cells are not clear so far. This research is aimed to the study of Bacillus
      intermedius RNase (binase) penetration in alveolar lung epithelial cells-
      pneumocytes of type II. Using immunofluorescence we have shown for the first time
      have internalization of binase by primary non-differentiated pneumocytes ATII.
      The enzyme did not penetrate in pneumocytes MLE-12, which also derived from type
      II cells. However, binase was cytotoxic towards tumor MLE-12 cells, but not ATII
      cells. The obtained results testified the higher sensitivity of tumor cells
      towards binase compared with normal cells, and also showed that penetration of
      the enzyme into alveolar cells did not directly correlated with the cell death.

PMID- 22856133
TI  - [Pharmacological activity echinochrome A singly and consisting of BAA "Timarin"].
AB  - Pharmacological activity of echinochrome A (EchA) alone and in the biologically
      active additives (BAA) "Timarin", administered per os has been investigated on
      volunteers. EchA decreased serum glutatione (GSH) and increased catalase activity
      1 h after treatment; catalase activity normalized, while GSH exceeded the initial
      level 3 h after the treatment. Changes in serum lipid spectrum, demonstrating
      reduction of the risk atherogenesis were determined.

PMID- 22856134
TI  - [Manganese in atherogenesis: detection, origin, and role].
AB  - The role of transition metal ions in atherogenesis is controversial; they can
      participate in the hydroxyl radical generation and catalyze the reactive oxygen
      species neutralization reaction as cofactors of antioxidant enzymes. Using EPR
      spectroscopy, we revealed that 70% of the samples of aorta with atherosclerotic
      lesions possessed superoxide dismutase activity, 100% of the samples initiated
      Fenton reaction and demonstrated the presence of manganese paramagnetic centers.
      The sodA gene encoding manganese-dependent bacterial superoxide dismutase was not
      found in the samples of atherosclerotic plaques by PCR using degenerate primers.
      The data obtained indicates the perspectives of manganese analysis as a marker
      element in the express diagnostics of atherosclerosis.

PMID- 22856135
TI  - [Antioxidant and antiaggregant effects of covalent bienzyme superoxide dismutase
      chondroitin sulfate-catalase conjugate in platelet interactions].
AB  - A covalent bienzyme superoxide dismutase-chondroitin sulfate-catalase conjugate
      (SOD-CHS-CAT) demonstrated the dose-dependent inhibitory action on induced
      aggregation of platelets in the presence of hydrogen peroxide. Antioxidant
      activity of SOD-CHS-CAT appeared at much lower doses than for other CAT
      derivatives. We detected the antiaggregation effect of SOD-CHS-CAT for platelet
      aggregation induced by ADP, serotonin, TRAP (with their different mechanism of
      action). Novel properties of SOD-CHS-CAT confirmed with its action agains spread
      eagle platelets on glass surface. The new characteristics of SOD-CHS-CAT
      conjugate underline the prospects of its biopharmaceutical development for
      antioxidant therapy.

PMID- 22856136
TI  - [Tissue-specific expression of hormonal carcinogenesis target genes in rats
      treated with polycyclic aromatic hydrocarbons].
AB  - We have investigated the effect of polycyclic aromatic hydrocarbons (PAHs) on
      estrogen-metabolizing genes CYP1A1, CYP1B1, CYP19 and ERalpha and cyclin D1
      genes, which control of cell division in estrogen-depended tissues. Treatment of
      rats with benzo(a)pyren (BP) or 3-methylcholantrene (MC) significantly up
      regulated CYP1A1, CYP1B1 gene expression in liver, uterus and ovary, whereas alfa
      naphthoflavone (alpha-NF) did not have any effect. The high level of aromatase
      gene (CYP19) expression was detected in ovary only. Treatment of rats with BP or
      MC significantly down-regulated expression of this gene (15- and 5,5-fold,
      respectively), whereas alpha-NF did not have any effect. BP produced an increase
      in ERalpha and cyclin D1 gene expression in rat liver. This effect was not seen
      with MC and alpha-NF. ERalpha and cyclin D1 mRNA levels were unchanged in uterus
      of rats after PAHs treatment. On the other hand, BP treatment caused an increase
      of the ERalpha and cyclin D1 mRNA levels (3,5- and 2,5-fold, respectively) in
      ovary, whereas MC and alpha-NF did not have any effects. Thus, our results give
      evidence for tissue-specific effects of PAHs on expression of genes, which
      participate in hormonal carcinogenesis. Moreover, the fact that BP and MC
      treatment affects the expression of estrogen-metabolizing genes and genes, which
      control of cell division, supports the view that PAHs may be one of the causes of
      endocrine disorder and consequent hormonal carcinogenesis.

PMID- 22856137
TI  - [Sulfated polysaccharides of brown seaweeds--ligands of toll-like receptors].
AB  - The interaction of sulfated polysaccharides--fucoidans from brown seaweeds
      Laminaria japonica, Laminaria cichorioides and Fucus evanescens with Toll-like
      receptors (TLRs) expressed on membranes of embryonic human kidney epithelial
      cells (HEK293-null, HEK293-TLR2/CD14, HEK293-hTLR4/CD14-MD2 and HEK293-hTLR2/6)
      was investigated. In vitro fucoidans specifically interacted with TLR-2, TLR-4,
      and the heterodimer TLR-2/6 resultated in activation of transcription nuclear
      factor NF-kappaB. Analysis of composition the hydrolyzed fucoidan from F.
      evanescens was carried out by gas-liquid chromatography and chromatography-mass
      spectrometry. Results indicated the absence of 3-3-hydroxytetradecanoic acid (3
      OHC14), the basic component of lipopolysaccharides in the preparation. Thus, the
      obtained results suggested that fucoidans from brown seaweeds possessing
      immunotropic activity are independent ligands for TLRs, and are able to induce
      genetically determined biochemical processes of protection organisms against
      pathogenic microorganisms.

PMID- 22856138
TI  - [Liposome formulations of combretastatin A4 and 4-arylcoumarin analog prodrugs:
      antitumor effect in the mouse model of breast cancer].
AB  - The antimitotic agent combretastatin A4 (CA-4) has been suggested as an
      antivascular agent for anticancer therapy relatively recently. To reduce systemic
      toxicity by means of administration in liposome formulations, in this study new
      lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analog (CA4
      Ole and ArC-Ole, respectively), have been synthesized: Liposomes of 100 nm mean
      diameter prepared on the basis of egg phosphatidylcholine and
      phosphatidylinositol from bakers yeast have been shown to include completely up
      to 10 mol. % of CA4-Ole, or 7 mol. % of ArC-Ole. Also, prodrug bearing liposomes
      decorated with tetrasaccharide selectin ligand Sialyl Lewis X (SiaLe(x)) have
      been constructed to achieve targeting to endothelium under neovascularization.
      The antitumor activity in vivo was studied in the model of slowly growing mouse
      breast cancer. Under the used dose (22 mg/kg) as well as the regimen of treatment
      (four injections, one per a week, starting from the appearance of palpable
      tumors) cytostatic CA-4 did not reveal any anticancer effect, and oppositely even
      stimulated tumor growth. Liposome formulations of CA4-Ole did not show such
      stimulation. However, to achieve pronounced antitumor effect, number of
      injections of liposomes should be apparently elevated. New antimitotic agent ArC
      revealed cytotoxic activity of only one tenth value obtained for CA-4 in vitro in
      the culture of human breast carcinoma cells. Nevertheless, in vivo in the mouse
      model of breast cancer this compound showed antitumor effect under double CA-4
      equivalent dose. The results demonstrate availability of SiaLe(x)-liposomes
      loaded with ArC-Ole: this preparation began to inhibit tumor growth already after
      the second injection. It is necessary further to choose doses and regimens of
      administration both for ArC and liposome formulations bearing ArC-Ole.

PMID- 22856139
TI  - [The influence of glucose on the free radical peroxidation of low density
      lipoproteins in vitro and in vivo].
AB  - It was shown that glucose in concentration 12.5-100 mM stimulated of Cu(2+)
      mediated free radical peroxidation of low density lipoproteins (LDL) from human
      blood plasma. On the base investigation of kinetic parameters of LDL peroxidation
      it was stated that intensification of this process in the conditions of our
      experiments is caused by formation of free radical intermediates of glucose
      autoxidation during active oxygen species generation in the presence of metal
      ions with variable valence. It was found that glucose level normalization in the
      blood of patients with type 2 diabetes during therapy accompanied by significant
      decreasing of LDL oxidizing. During therapy with sugar-lowering drug metformin
      which utilizate methylglyoxal the LDL peroxidation from blood diabetes mellitus
      in vivo inhibited in more higher degree probably in consequence of decreasing of
      methylglyoxal-dependent generation of superoxide anion radicals as was shown by
      us early [Biochemistry (Moscow), 2007, 72: 1081-1090; Biochemistry (Moscow),
      20(09, 74: 461-466].

PMID- 22856140
TI  - [Role of phospholipase D in metabolism reactions of transgenic tobacco cax1 cells
      under salinity stress].
AB  - The work was aimed at investigation of primary reactions of plant cell metabolism
      in response to salt stress influence. It was found that phospholipase D
      regulatory enzyme is activated in wild type tobacco plants and transgenic cax1
      tobacco plants during the early stages of salt stress influence. We have shown
      that disturbance of intracellular calcium ions homeostasis and oppression of
      phospholipase D activity decrease resistance of tobacco plants under salinity
      influence and also indicate the implication of such systems to signaling during
      stress adaptation of plants.

PMID- 22856141
TI  - [Identification of genes that promote awnedness in the Triticum aestivum/Aegilops
      umbellulata introgressive line].
AB  - Genetic analysis of Triticum aestivum/Aegilops umbellulata introgressive line for
      the character ear awnedness has been realized. According to the studying the
      lines and hybrids for the characters awnedness and electrophoresis spectra of
      microsatellite components the digenic model for control of awnedness is
      suggested. The model supposes participation of gene--inhibitor of awnedness B1
      (5AL) and gene--promoter of awnedness Awn1 in chromosome 6U of Aegilops
      umbellulata. Chromosome 5A of the awned line is rearranged relative to the same
      chromosome of the Aurora genotype. The distance between the Xwmc705-5AL SSR-locus
      and rearranged fragment or locus B1/b1 is determined as 15,5 cM.

PMID- 22856142
TI  - [Ultrastructure and metabolic activity of pea mitochondria under clinorotation].
AB  - Experimental data on the mitochondrial ultrastructure and tissue respiration in
      root apex as well as metabolic activity of the organelles isolated from pea
      seedling roots after 5-day of clinorotation are presented. It was shown that
      mitochondrial condensation in the distal elongation zone correlated with an
      increased rate of oxygen uptake on 7%. We also observed increase in rate of
      malate oxidation and respiratory control ratio increased simultaneously with a
      decreased in efficiency of oxidative phosphorylation. Such character of
      mitochondrial rearrangements in simulated microgravity is assumed to be a
      consequence of adaptation to these conditions.

PMID- 22856143
TI  - [Features of lettuce transgenic plants with ifn-alpha2b gene regenerated after
      Agrobacterium rhizogenes-mediated transformation].
AB  - "Hairy" roots of lettuce Lactuca sativa and regenerated plants with interferon
      alpha2b gene had been obtained via Agrobacterium rhizogenes-mediated
      transformation. According to the results of PCR and rt-PCR analyses the studied
      plants had ifn-alpha2b gene. The regenerated plants differed from the plants of
      wild type by elongated internodes, early flower-bearing stem formation and purple
      coloration of leaves in artificial illumination conditions.

PMID- 22856144
TI  - [Lewis lung carcinoma variant with high sensitivity to antitumor antiangiogenic
      therapy reveals a high capacity to autophagy].
AB  - Comparative investigation of two variants of Lewis lung carcinoma cells (LLC and
      LLC/R9) growing under nutrient deficiency caused by long-term incubation without
      growth medium replacement was performed. It was established that LLC/R9 cells
      which in contrast to LLC cells had a high sensitivity to antitumor antiangiogenic
      therapy (AAT) revealed a high dependence of their survival from glucose level in
      growth medium as well as high capacity to autophagy under nutrient deficiency.
      Perhaps high autophagy activity in tumor cells may be considered as a marker of
      tumor AAT sensitivity.

PMID- 22856145
TI  - [Oxidoreductase expression and protein storage in winter and spring cereals under
      extremal temperature condition].
AB  - Cultivation of wheat and barley plants under temperature stress fluctuations was
      the reason of reduction of acid protein common storage in the tissues more than
      25% and the reason of reduction of peroxidase and superoxide dismutase common
      activities. There were no changes of common phenoloxidase activity. Activity
      redistribution between separate fractions of enzyme spectra were linked with
      enzyme expression changes. Alteration of peroxidase/oxidase ratio for separate
      fractions of electrophoretical spectra has been defined as a result of extreme
      temperature influence over a period of plant growing. At the same time there were
      no alterations in peroxidase/superoxide reductase fraction ratio in seedlings.
      The Vrn1-loci did not have a single meaning for expression of investigated
      oxidoreductases because their influence was determined by the "organism
      environment" definite situation. In "normal" growth circumstances there was no
      correlation between the type of development and qualitative and quantitative
      characteristics of oxidoreductase spectra. The alteration of definite enzyme
      izoform degree in forming of plant stress response was different for spring and
      winter genotypes that testifies dependence of the functional state of the probed
      enzymes on allelic composition of locus Vrn1.

PMID- 22856146
TI  - [Docking of low-molecular ligands on the plant FtsZ-protein with application of
      CUDA-accelerated calculations].
AB  - This article provides review and analysis of opportunities for application of the
      CUDA technology for acceleration of computations in structural biology and
      bioinformatics. On the example of work with the Hex 6.1 program, comparative
      analysis of increase in the speed and quality of results of hard-docking of a
      number of low-molecular compounds on the surface of the FtsZ protein from
      Arabidopsis thaliana was performed. Several potential benzimidazole--plant FtsZ
      protein binding sites were identified.

PMID- 22856147
TI  - [The role of some donor-host cell interactions in conditions of the regenerative
      process microenvironment].
AB  - The review is devoted to the analysis of experimental data about possible
      mechanisms of transdifferentiation or plasticity of tissue specific stem cells.
      Considerable attention is focused on the mechanisms and genetic consequences of
      fusion of different types of donor cells with the cells of recipient tissues
      which investigated on the models of cellular therapy of liver and heart diseases.
      The role of various kinds of cell contacts and their role in stem cells
      integration, reparation and regeneration of injured tissue and horizontal genes
      transfer are considered.

PMID- 22856148
TI  - [Cytomixis, its nature, significance and the cytological consequences].
AB  - Cytomixis is the widespread natural process of intercellular interaction which is
      characteristic for vegetative and generative tissues in both normal and
      pathological conditions. The origin significance and genetic control cytomixis
      still remain not completely clear. The popularity of view of the pathological
      nature of cytomixis based on its peculiar plants with genetic instability and
      impaired homeostasis. In the genetic control of cytomixis seem to be involved
      meiotic genes which are responsible for segregation and organization of
      chromosomes. Their activity is modified by environmental factors through signal
      transduction. It is assumed via cytomixis, from one side, the informational
      contact can be reached and meiosis and gametogenesis are synchronized, with
      another, increase of the genetic variety and level of the heterozygosis of
      microsporocytes. The activity of cytomixis varies over wide limits. The greatest
      influence on its activity have mutagenesis hybridization and polyploidy. In this
      context cytomixis can fulfill the function of cell selection which is activated
      by exceeding of the threshold level of the microsporocyte damages (or genetical
      disbalance).

PMID- 22856149
TI  - [Structural and functional characteristics of betulin derivatives].
AB  - The effect of betulin derivatives on persistence properties of microorganisms was
      studied in vitro. It was shown that the antipersistence action of the betulin
      derivatives depended on their structure and the microbial species. The
      experimental data on the structure - function relation could be useful in
      development and synthesis of new agents for therapy of chronic infections
      associated with persistence of bacterial pathogens in macroorganism.

PMID- 22856150
TI  - [Comparative study of antiviral activity of luteolin and 7,3'-disulfate
      luteolin].
AB  - Antiviral activity of 7,3'-disulfate luteolin, extracted from Zostera marina was
      studied on an experimental model of tick-borne encephalitis (TBE) in vivo and in
      vitro. The drug increased the survival of the experimental mice infected with TBE
      virus and prolonged their lifespan. It was shown that 7,3'-disulfate luteolin
      reduced the virus accumulation in the SPEV cells by 2.0-4.0 lg TCID50/ml.

PMID- 22856151
TI  - [Influence of rimantadine, ribavirine and triazavirine on influenza A virus
      replication in human monolayer and lymphoblastoid cell lines].
AB  - The influence of antivirals, such as rimantadine, ribavirine and triazavirine on
      influenza virus replication in human cell cultures was evaluated. All the
      antivirals inhibited viral nucleoprotein NP synthesis. The strongest effect was
      shown for ribavirine in lung carcinoma A-549 cells and endothelial ECV-304 cells.
      Hoechst-33258 staining revealed induction of apoptosis in all the cell lines.
      Rimantadine and ribavirine inhibited virus-induced apoptosis while ribavirine
      enhanced it. The effect was registered in monolayer cell cultures as well as in
      suspension cell cultures. The influence of the antiviral drugs on the virus
      induced cell proliferation in the suspension cell cultures is also described.

PMID- 22856152
TI  - [Spectrophotometric determination of cefazolin in mixed saliva of practically
      healthy subjects and patients with infective somatic pathology].
AB  - The behaviour of cefazolin in aqueous and biological media with varying the
      antibiotic concentration was studied by UV-spectroscopy. Range of the contents
      and the detection limits of cefazolin were determined. The procedure of UV
      spectroscopy of cefazolin in mixed saliva of patients with urinary tract
      infection was developed.

PMID- 22856153
TI  - [Interferon inductors in treatment of associative forms of tick-borne infection
      in children].
AB  - Thirty three children with associative forms of thick-borne infection (thick
      borne encephalitis with ixodic borreliosis) were clinically observed. The disease
      was characterized by subfebrile temperature, moderate intoxication, rare erythema
      (39.5%) and frequent cardiovascular disorders with development of Lyme carditis
      (32.6 +/- 7.2%) and further rise of hepatomegalia in the diseases dynamics and
      development of meningeal symptoms. There were observed changes in the cytokine
      spectrum, characterized by INF-gamma high levels, and hypersecretion of the whole
      spectrum cytokines in the dynamics, that provided the Th2 type immune response.
      High clinicoimmunological efficacy of the complex therapy with cycloferon as an
      immunomodulator providing more balanced production of pro- and anti-inflammatory
      cytokines (IL-1alpha, INF-gamma and IL-10) was shown.

PMID- 22856154
TI  - [Combined therapy of patients with recurring anogenital herpes infection].
AB  - Up-to-date conceptions of etiology and epidemiology of anogenital herpetic
      infection are described. The main mechanisms of immunological shifts in subjects
      with anogenital Herpes infection are discussed. The efficacy and safety of
      cycloferon in the combined treatment of patients with recurring anogenital
      herptic infection were estimated. The clinical efficacy of the combined therapy
      (acyclovir in a dose of 200 mg 5 times a day for 5 days + cycloferon liniment
      applied topically on the eruptions twice a day for 5 days) was 85% or 25% higher
      vs. the control.

PMID- 22856155
TI  - [Biologically active nonribosomal peptides. II. Nonribosomal peptides of various
      biological action].

PMID- 22856156
TI  - [Present stage of chemotherapy and chemoprophylaxis of rickettsiosis and Q
      fever].
AB  - The analysis of the published experimental and clinical data on chemoprophylaxis
      and chemotherapy of rickettsiosis and Q fever confirmed the preserved role of
      doxycycline, the main drug of choice in the treatment of the diseases, then
      followed chloramphenicol. Macrolides, such as azithromycin and clarithromycin
      proved to be useful in pediatric practice and the treatment of pregnant women
      with rickettsiosis. The treatment of acute and chronic Q fever required the use
      of doxycycline, fluoroquinolobes, co-trimoxazole and hydroxachloroquine in
      combined therapy. It is concluded that in vivo studies of novel drugs and
      investigation of prospective macrolides and fluoroquinolones are necessary.
      Clinical trials of a new glycycline, i.e. tigecycline, which experimentally
      showed highy strong activity against the Q fever pathogen, should be accelerated.

PMID- 22856157
TI  - [Cardiology and cardiosurgery--innovative development].

PMID- 22856158
TI  - [Protective systems of the human organism as a basis of search and development of
      new original medical drugs].

PMID- 22856159
TI  - [Strategy of innovative development of Federal Organization "E.N. Meshalkin
      NSRICD" of the Russian Federation Ministry of Health Care and Social Development
      as a part of the program "Cardio-vascular diseases"].

PMID- 22856160
TI  - [Development of scientific researches in the Siberian Department of the Russian
      Academy of Medical Sciences as a part of the programm "Cardio-vascular
      diseases"].

PMID- 22856161
TI  - [Cardio-vascular diseases in 21th century: new challenges and new solutions].

PMID- 22856162
TI  - [The presidium resolution on development of scientific researches and
      infrastructure as a part of the programm "Cardio-vascular diseases"].

PMID- 22856163
TI  - [Treatment of HIV-infection by means of gene therapy].
AB  - Current methods of HIV treatment can contain a progression of the disease;
      however they do not lead to a cure. Lifelong antiretroviral therapy is therefore
      necessary, leading to problems of cost and toxicity of chemical drugs. The recent
      advances in science have allowed a new approach to the HIV-treatment - gene
      therapy. In the present publication we focus on one strategy of the gene therapy
      called "intracellular immunization". The strategy is based on the introducing of
      antiviral genes into the HIV-sensitive cells. We highlight the mechanisms of
      action of various antiviral genetic agents and discuss some issues concerning
      target cells and genes delivery. Finally we summarize the results of certain gene
      therapy clinical trials.

PMID- 22856164
TI  - [Evaluation of association between 9 genetic polymorphism and myocardial
      infarction in the Siberian population].
AB  - AIM: to evaluate association between genetic polymorphism (SNPs) and myocardial
      infarction (identified in recent GWAS) as markers of high risk of myocardial
      infarction (MI) in Siberian population. Patients were divided into 2 groups - MI
      patients and control group (ratio 1:2) and presented the sapmle of population of
      Novosibirsk (9400 patients, 45-69 years) within international project HAPIEE
      (Health, Alcohol and Psychosocial factors In Eastern Europe). 200 patients with
      MI (129 men, 71 women) were included. Control group - individuals without MI
      (420) matched for age and sex. Genomic DNA was extracted from venous blood by
      phenol-chloroform extraction. Gene polymorphism of genes tested by real-time PCR
      according to protocol (probes TaqMan, Applied Biosystems, USA) with the use of
      ABI 7900HT. The following SNPs were studied: rs28711149, rs499818, rs619203,
      rs10757278 and rs1333049 (hr. 9), rs1376251, rs2549513, rs4804611, rs17465637.
      The association of SNP and MI was confirmed for 4 of 9 studied SNPs: rs1333049
      (hr. 9), rs10757278 (hr. 9), rs499818 (hr. 6), rs619203 gene ROS1. Heart rate was
      associated with rs1333049 and rs10757278. Glucose level was associated with
      rs619203, rs28711149 and rs1376251. Total cholesterol and atherogenic index was
      associated with rs28711149. For the first time in Russian population the
      associations of GWAS with myocardial infarction SNPs was detected for rs619203,
      rs499818, rs1333049 and rs10757278. These genetic markers can be used for
      assessing the risk of myocardial infarction in Russian population.

PMID- 22856165
TI  - [Sarcoidosis: problems in classification].
AB  - In this article the authors discuss the issues related to assessment of activity
      and severity of sarcoidosis, course and radiographic manifestations of this
      disease. Problems in defining of different forms of sarcoidosis resulted in
      suggestion of new version of classification.

PMID- 22856166
TI  - [About experience of producing city health profile as a part of the international
      who healthy cities project].
AB  - The article presents information about the international project "Healthy
      cities", knowledge about principles and axioms of the project. The authors have
      analyzed the experience of producing the "City Health Profile" under the project
      WHO "Healthy cities". The authors believe that the "Health Profile" of each
      individual city varies depending on specific conditions, both physical (the size
      of the territory, the state of the environment, its location) and political, and
      socio-economic. However, the formation of the "City Health Profile" is
      universally, regardless of geographical location or structure. It was noted that
      the "City Health Profile" has reflected all aspects of the life of the city,
      facilitates or barriers the promotion of inhabitants' health and their well
      being. For producing of "City Health Profile" additional data are needed: survey,
      sociological polls of the city population (self-assessment of their health
      status, lifestyle and quality of life). The advantage of these researches,
      carried out in the framework of the project "Healthy Cities", is implementation
      of complex sociological survey with a focused multi-purpose monitoring, covering
      all spheres of life in the city, to present a versatile, complete and objective
      evidences to illustrate the city as a territory of health and make up the
      holistic picture and the centre of which is the citizen and his/her health
      according to the WHO recommendations.

PMID- 22856167
TI  - [Improvement of health care for patients with upper respiratory tract diseases
      associated with chlamydia infection].
AB  - At present the issues in regard to Chlamydia infection are not only limited by
      urogenital system. By the way optimal organization and non-urogenital
      chlamydiosis treatment strategy (with respiratory tract involvement in
      particular) have not been worked out yet and require immediate solutions. Due to
      new knowledge on respiratory chlamidiosis the authors discuss scientific
      background for future development of complex measures and main directions of
      health care support strategy for patients with upper respiratory associated with
      Chlamydia infection.

PMID- 22856168
TI  - [Mechanisms of protective influence of endotoxin-activated Kupffer cells on
      hepatocytes].
AB  - Various aspects of protective and damaging influences of endotoxin-activated
      Kupffer cells on hepatocytes are discussed. Requests for protective subcellular
      mechanism activated by Kupffer cells mediators were formulated. Two possible
      mechanisms of activated Kupffer cells protective influence on hepatocytes which
      satisfy these requests are considered. One of them may operate via hepatocyte non
      specific reaction to damage initiated by Kupffer cells mediators. Another one may
      work through activation of endotoxin-dependent tissue stress mechanism in
      hepatocytes. The data confirm the development of non-specific reaction to damage
      and the mechanism of tissue stress realized by means of tissue-specific effector
      in hepatocytes under endotoxin-activated Kupffer cells influence.

PMID- 22856169
TI  - [Role of dopamine D1- and D2-receptors in the delta1-opioidergic
      immunostimulation].
AB  - The study has shown that activation of delta1-opioid receptors by a highly
      selective peptide agonist DPDPE (100 microg/kg) results in a significant increase
      of the immune response to antigen (SRBC, 5 x 10(8)) in CBA mice. SCH-23390 (1
      mg/kg), a selective antagonist of the postsynaptic dopamine D1-receptors, and
      selective D2-blocker haloperidol (1 mg/kg) prevented immunostimulating effect of
      DPDPE. Comparison of effects of the antagonists suggests that delta1-opioidergic
      immunostimulation has more significant impact due to involvement of dopamine D1
      receptors.

PMID- 22856170
TI  - [Molecular mechanisms of formation of blood eosinophilia under pulmonary
      tuberculosis].
AB  - Molecular factors of pathogenesis of the eosinophilic blood reaction under
      pulmonary tuberculosis are analyzed in the article. It has been established that
      the key cytokine providing the development of hemic eosinophilia in patients with
      pulmonary tuberculosis is IL-5. IL-5 plasma concentration turned out to be
      increased only in patients with eosinophilia. Increase of eotaxin was determined
      in patients with tuberculosis despite of the presense of eosinophilia. One
      directional nature of the defined changes in eotaxin concentration might be
      explained by dual properties of this chemokine: on the one hand, eotaxin mediates
      long-term presence of eosinophils in blood; on the other hand, it initiates the
      process of adhesion of eosinophilic leucocytes to vascular endothelium with their
      further migration to the focus of granulomatous inflammation. The established
      increase in number of IL-5R-positive eosinophils presents one more mechanism
      which explains the basis of long-term presence of eosinophils in peripheral blood
      in patients with pulmonary tuberculosis.

PMID- 22856171
TI  - [Gnotobiology in modern bio-medical research].
AB  - An overview of the present status and prospects of gnotobiology along with a role
      of normal microflora studied using laboratory animals with controlled microflora
      (gnotobiotes) is presented. The principal elements of gnotobiotechnology as well
      as possibilities of its using in both experimental and clinical investigations
      are analyzed. A multifaceted role of normal microflora in the host physiology and
      pathology prejudge the increasing importance of gnotiological models in various
      fields of biology and medicine, such as the development of new generations
      probiotics. An assessment and characteristics of selected microbial strains, host
      microbe interactions etc. An organization of further complex gnotobiotic research
      is of prospective value.

PMID- 22856172
TI  - Social enterprise in health organisation and management: hybridity or
      homogeneity?
AB  - PURPOSE: The purpose of this paper is to reflect on social enterprise as an
      organisational form in health organisation and management.
      DESIGN/METHODOLOGY/APPROACH: The paper presents a critique of the underlying
      assumptions associated with social enterprise in the context of English health
      and social care. FINDINGS: The rise of social enterprise models of service
      provision reflects increasingly hybrid organisational forms and functions
      entering the health and social care market. Whilst at one level this hybridity
      increases the diversity of service providers promoting innovative and responsive
      services, the paper argues that further inspection of the assumptions associated
      with social enterprise reveal an organisational form that is symbolic of
      isomorphic processes pushing healthcare organisations toward greater levels of
      homogeneity, based on market-based standardisation and practices. Social
      enterprise forms part of isomorphic processes moving healthcare organisation and
      management towards market norms". ORIGINALITY/VALUE: In line with the aim of the
      "New Perspectives section", the paper aims to present a provocative perspective
      about developments in health and social care, as a spur to further debate and
      research in this area.

PMID- 22856173
TI  - Managing in the context of healthcare's escalating technology and evolving
      culture.
AB  - PURPOSE: As healthcare has become more scientifically based and far more
      sophisticated in terms of technology, it has become more fragmented in terms of
      care-giving, and less personal. The purpose of this paper is to discuss the
      challenging task of leading and managing in the gap between the existing and
      emerging cultures of healthcare. DESIGN/METHODOLOGY/APPROACH: This paper
      considers the literature on culture, how it exists at many levels and in multiple
      forms, and the impacts it has on the US healthcare system. Further, the paper
      explores foundations of the current healthcare culture and attempts to forecast
      features of the emerging culture, incorporating examples of advances in
      scientific knowledge and technology. FINDINGS: System change will continue to be
      problematic until leaders and change agents find ways to operate effectively in
      the gap between the existing cultural tenets and those emerging as the result of
      scientific and technological advancements. ORIGINALITY/VALUE: Punctuated
      equilibrium theory serves as a main tenet for describing how changes will
      continue to push the USA towards a cultural tipping point. This paper contends
      that leaders and managers can succeed only by understanding and respecting both
      cultures and calls for improved theory development and research to help find
      creative ways to advance the new culture without trampling the old.

PMID- 22856174
TI  - Quality improvement through clinical communities: eight lessons for practice.
AB  - PURPOSE: Approaches to quality improvement in healthcare based on clinical
      communities are founded in practitioner networks, peer influence and professional
      values. However, evidence for the value of this approach, and how to make it
      effective, is spread across multiple disciplines. The purpose of this paper is to
      review and synthesise relevant literature to provide practical lessons on how to
      use community-based approaches to improve quality. DESIGN/METHODOLOGY/APPROACH:
      Diverse literatures were identified, analysed and synthesised in a manner that
      accounted for the heterogeneity of methods, models and contexts they covered.
      FINDINGS: A number of overlapping but distinct community-based approaches can be
      identified in the literature, each suitable for different problems. The evidence
      for the effectiveness of these is mixed, but there is some agreement on the
      challenges that those adopting such approaches need to address, and how these can
      be surmounted. PRACTICAL IMPLICATIONS: Key lessons include: the need for co
      ordination and leadership alongside the lateral influence of peers; advantages of
      starting with a clear programme theory of change; the need for training and
      resources; dealing with conflict and marginalisation; fostering a sense of
      community; appropriate use of data in prompting behavioural change; the need for
      balance between "hard" and "soft" strategies; and the role of context.
      ORIGINALITY/VALUE: The paper brings together diverse literatures with important
      implications for community-based approaches to quality improvement, drawing on
      these to offer practical lessons for those engaged in improving healthcare
      quality in practice.

PMID- 22856175
TI  - Organisational culture and change: implementing person-centred care.
AB  - PURPOSE: The purpose of this paper is to explore the connection between
      organisational cultures and the employee's resistance to change at five hospital
      wards in Western Sweden. Staff had experienced extensive change during a research
      project implementing person-centred care (PCC) for patients with chronic heart
      failure. DESIGN/METHODOLOGY/APPROACH: Surveys were sent out to 170 nurses. The
      survey included two instruments--the Organisational Values Questionnaire (OVQ)
      and the Resistance to Change Scale (RTC). FINDINGS: The results indicate that a
      culture with a dominating focus on social competence decreases "routine seeking
      behaviour", i.e. tendencies to uphold stable routines and a reluctance to give up
      old habits. The results indicate that a culture of flexibility, cohesion and
      trust negatively covariate with the overall need for a stable and well-defined
      framework. PRACTICAL IMPLICATIONS: An instrument that pinpoints the conditions of
      a particular healthcare setting can improve the results of a change project.
      Managers can use instruments such as the ones used in this study to investigate
      and plan for change processes. ORIGINALITY/VALUE: Earlier studies of
      organisational culture and its impact on the performance of healthcare
      organisations have often investigated culture at the highest level of the
      organisation. In this study, the culture of the production units--i.e. the health
      workers in different hospital wards--was described. Hospital wards develop their
      own culture and the cultures of different wards are mirrored in the hospital.

PMID- 22856176
TI  - A systems perspective on nursing productivity.
AB  - PURPOSE: Recent New Zealand reports have identified the nursing workforce for its
      potential to make a significant contribution to increased productivity in health
      services. The purpose of this paper is to review critically the recent and
      current labour approaches to improve nursing productivity in New Zealand, in a
      context of international research and experience. DESIGN/METHODOLOGY/APPROACH: An
      examination of government documents regarding productivity, and a review of New
      Zealand and international literature and research on nursing productivity and its
      measurement form the basis of the paper. FINDINGS: It is found that productivity
      improvement strategies are influenced by theories of labour economics and
      scientific management that conceptualise a nurse as a labour unit and a cost to
      the organisation. Nursing productivity rose significantly with the health reforms
      of the 1990s that reduced nursing input costs but impacts on patient safety and
      nurses were negative. Current approaches to increasing nursing productivity,
      including the "productive ward" and reconfiguration of nursing teams, also draw
      on manufacturing innovations. Emerging thinking considers productivity in the
      context of the work environment and changing professional roles, and proposes
      reconceptualising the nurse as an intellectual asset to knowledge-intensive
      health organisations. PRACTICAL IMPLICATIONS: Strategies that take a systems
      approach to nursing productivity, that view nursing as a capital asset, that
      focus on the interface between nurse and working environment and measure patient
      and nurse outcomes are advocated. ORIGINALITY/VALUE: The paper shows that
      reframing nursing productivity brings into focus management strategies to raise
      productivity while protecting nursing and patient outcomes.

PMID- 22856177
TI  - Radical change in healthcare organization: mapping transition between templates,
      enabling factors, and implementation processes.
AB  - PURPOSE: The purpose of this paper is to examine: the content of radical change
      by mapping differences between two templates for organizing delivery of
      healthcare; the enabling and constraining mechanisms underlying major change from
      one template to another; and the processes implicated in change implementation.
      DESIGN/METHODOLOGY/APPROACH: Longitudinal, qualitative case study design allowed
      the tracking, over a four-year period, of the transformation of healthcare
      service in a community from provider-centered, fragmented delivery to patient
      centered, integrated delivery. The authors conducted 90 interviews at three
      intervals, observed meetings, and analyzed internal and external documents.
      Concepts on content, process and mechanisms were used to analyze the data.
      FINDINGS: Transition from one template to another involves radical change in
      structures/systems and underlying values. Mechanisms precipitating and enabling
      change include: powerful stakeholders' dissatisfaction with current template and
      commitment to a new one, willingness to resource the change, provision of
      credible leadership, and manipulation of incentive programs. Radical change is
      underlain by a series of micro change processes that involve emergent, non-linear
      dynamics, and that follow their own track with enabling and constraining
      mechanisms. ORIGINALITY/VALUE: The paper describes a case of positive, successful
      change. Implications include importance of: attention to power dynamics,
      persistent leadership, elimination of boundaries between collaborating groups,
      and aligning incentives with desired practice changes; and attending to both
      variance and process in understanding healthcare change.

PMID- 22856178
TI  - Implementing organisation and management innovations in Swedish healthcare:
      lessons from a comparison of 12 cases.
AB  - PURPOSE: The purpose of this paper is to compare the implementation of 12
      different organisation and management innovations (OMIs) in Swedish healthcare,
      to discover the generic and specific factors important for successful healthcare
      improvement change in a public health system. DESIGN/METHODOLOGY/APPROACH:
      Longitudinal cross-case comparison of 12 case studies was employed, where each
      case study used a common framework for collecting data about the process of
      change, the content of the change, the context, and the intermediate and final
      outcomes. FINDINGS: Clinical leaders played a more important part in the
      development of these successful service innovations than managers. Strategies for
      and patterns of change implementation were found to differ according to the type
      of innovation. Internal organisational context factors played a significant role
      in the development of nearly all, but external factors did not. "Developmental
      evolution" better described the change process than "implementation". RESEARCH
      LIMITATIONS/IMPLICATIONS: The 12 cases were all of relatively successful change
      processes: some unsuccessful examples would have provided additional testing of
      the hypotheses about what would predict successful innovation which were used in
      the case comparison. The cross-case comparative hypothesis testing method allows
      systematic comparison if the case data are collected using similar frameworks,
      but this approach to management research requires considerable resources and
      coordination. PRACTICAL IMPLICATIONS: Management innovations that improve patient
      care can be carried out successfully by senior clinicians, under certain
      circumstances. A systematic approach is important both for developing and
      adapting an innovation to a changing situation. A significant amount of time was
      required for all involved, which could be reduced by "fast-tracking" approval for
      some types of change. ORIGINALITY/VALUE: This is the first empirical report
      comparing longitudinal and contextualised findings from a number of case studies
      of different organisational and management healthcare innovations. The findings
      made possible explanations for success factors and useful practical
      recommendations for conditions needed to nurture such innovation in public
      healthcare.

PMID- 22856179
TI  - Determinants of managerial competencies for primary care managers in Southern
      Thailand.
AB  - PURPOSE: The purpose of this paper is first, to identify the critical managerial
      competencies of primary care managers; and second, to determine the relationship
      between personality and motivation, and managerial competency.
      DESIGN/METHODOLOGY/APPROACH: A survey was conducted involving distribution of
      questionnaires to 358 rural primary care managers in Southern Thailand. FINDINGS:
      The survey found six critical managerial competencies: visionary leadership;
      assessment, planning, and evaluation; promotion of health and prevention of
      disease; information management; partnership and collaboration; and
      communication. Both personality and motivation are found to significantly
      influence primary care managers' managerial competency. In particular,
      conscientiousness (i.e. perseveres until the task is finished, does a thorough
      job, full of energy, does things efficiently, and a lot of enthusiasm) is related
      to all managerial competencies. It is clear that extrinsic and intrinsic factors
      (i.e. quality of supervision and leadership, organizational policy and
      administration, interpersonal relationship, working conditions, work itself,
      amount of responsibility, and job recognition) are influential in primary care
      manager motivation that can significantly improve morale. RESEARCH
      LIMITATIONS/IMPLICATIONS: The short version of the personality instrument may
      limit the generalization of some of the findings. Future research is needed to
      assess the relationship between managerial competency and performance. Further
      research could be done in other countries to see if this conclusion is in fact
      correct. It would also be useful to research if the findings apply to other
      health and social areas. PRACTICAL IMPLICATIONS: Personality and motivation are
      able to co-predict managerial competency whereby motivation tends to have a
      stronger influence than personality. These findings will be useful to policy
      makers and to those responsible for the human development in the preparation of
      management training and development programs. Moreover, top management should not
      overlook the motivational system as a way to encourage managers to be competent
      in their job. ORIGINALITY/VALUE: The paper contributes to our understanding of
      managerial competency within the context of rural primary care sectors. The
      success of any organized health program depends upon effective management, but
      health systems worldwide face a lack of competent management at all levels.
      Management development for health systems, particularly at the first line of
      supervision, must be given much higher priority for investment.

PMID- 22856180
TI  - Epidemiologic characterization of Colorado backyard bird flocks.
AB  - Backyard gallinaceous bird flocks may play an important role in the spread of
      infectious diseases within poultry populations as well as the transmission of
      zoonotic diseases to humans. An epidemiologic characterization was conducted of
      Colorado backyard flocks to gather information on general flock characteristics,
      human movement of birds, human-bird interaction, biosecurity practices, and flock
      health. Our results suggest that backyard poultry flocks in Colorado are small
      sized flocks (68.6% of flocks had < 50 birds); consist primarily of layer
      chickens (85.49% of flocks), show chickens (32.18% of flocks), and waterfowl
      (34.07% of flocks); and are primarily owned for food (meat or egg) production for
      the family (86.44%) or as pet or hobby birds (42.27%). The backyard flock
      environment may promote bird-to-bird transmission as well as bird-to-human
      transmission of infectious disease. Birds are primarily housed with free access
      to the outside (96.85%), and many are moved from the home premises (46.06% within
      1 yr). Human contact with backyard flocks is high, biosecurity practices are
      minimal, and bird health is negatively impacted by increased movement events.
      Increased knowledge of backyard bird characteristics and associated management
      practices can provide guidelines for the development of measures to decrease
      disease transmission between bird populations, decrease disease transmission from
      birds to humans, and increase the overall health of backyard birds.

PMID- 22856181
TI  - The efficacy of three commercial Mycoplasma gallisepticum vaccines in laying
      hens.
AB  - The efficacy of three commercial Mycoplasma gallisepticum (MG) immunizing agents
      a bacterin, a recombinant fowlpox-MG vaccine, and a live F-strain vaccine-was
      compared in specific-pathogen-free hens in egg production. Three groups of 25
      chickens were vaccinated with one of the vaccines at 10 wk of age and 25 birds
      were not vaccinated. At 25 wk of age (and approximately 50% egg production), 20
      birds from each of the three vaccinated groups and 15 nonvaccinated controls were
      challenged with virulent R-strain via aerosol; the birds were necropsied and
      evaluated at 10 days post-challenge. The MG bacterin and live F-strain
      vaccinations were both protective and resulted in significant differences in air
      sac lesions, tracheal lesions, and ovarian regression compared to the
      nonvaccinated controls and the recombinant fowlpox-MG vaccine (P < or = 0.05).
      The evaluation of ovarian regression is a useful method of testing the efficacy
      of MG vaccines in laying hens.

PMID- 22856182
TI  - Low pathogenicity avian influenza viruses infect chicken layers by different
      routes of inoculation.
AB  - In order to develop better control measures against avian influenza, it is
      necessary to understand how the virus transmits in poultry. In a previous study
      in which the infectivity and transmissibility of the pandemic H1N1 influenza
      virus was examined in different poultry species, we found that no or minimal
      infection occurred in chicken and turkeys intranasally (IN) inoculated with the
      virus. However, we demonstrated that the virus can infect laying turkey hens by
      the intracloacal (IC) and intraoviduct (IO) routes, possibly explaining the drops
      in egg production observed in turkey breeder farms affected by the virus. Such
      novel routes of exposure have not been previously examined in chickens and could
      also explain outbreaks of low pathogenicity avian influenza (LPAI) that cause a
      decrease in egg production in chicken layers and breeders. In the present study,
      46-wk-old specific-pathogen-free chicken layers were infected by the IN, IC, or
      IO routes with one of two LPAI viruses: a poultry origin virus,
      A/chicken/CA/1255/02 (H6N2), and a live bird market isolate,
      A/chicken/NJ/12220/97 (H9N2). Only hens IN inoculated with the H6N2 virus
      presented mild clinical signs consisting of depression and anorexia. However, a
      decrease in number of eggs laid was observed in all virus-inoculated groups when
      compared to control hens. Evidence of infection was found in all chickens
      inoculated with the H6N2 virus by any of the three routes and the virus
      transmitted to contact hens. On the other hand, only one or two hens from each of
      the groups inoculated with the H9N2 virus shed detectable levels of virus, or
      seroconverted and did not transmit the virus to contacts, regardless of the route
      of inoculation. In conclusion, LPAI viruses can also infect chickens through
      other routes besides the IN route, which is considered the natural route of
      exposure. However, as seen with the H9N2 virus, the infectivity of the virus did
      not increase when given by these alternate routes.

PMID- 22856183
TI  - Advancement in vaccination against Newcastle disease: recombinant HVT NDV
      provides high clinical protection and reduces challenge virus shedding with the
      absence of vaccine reactions.
AB  - Newcastle disease (ND) is a highly contagious disease of chickens causing
      significant economic losses worldwide. Due to the limitation in their efficacy,
      current vaccination strategies against ND need improvements. This study aimed to
      evaluate a new-generation ND vaccine for its efficacy in providing clinical
      protection and reducing virus shedding after challenge. Broiler chickens were
      vaccinated in ovo or subcutaneously at hatch with a turkey herpesvirus-based
      recombinant vaccine (rHVT) expressing a key protective antigen (F glycoprotein)
      of Newcastle disease virus (NDV). Groups of birds were challenged at 20, 27, and
      40 days of age with a genotype V viscerotropic velogenic NDV strain. Protection
      was 57% and 81%, 100% and 95%, and 100% and 100% after the subsequent challenges
      in the in ovo and subcutaneously vaccinated chickens, respectively. Humoral
      immune response to vaccination could be detected from 3-4 wk of age. Challenge
      virus shedding was lower and gradually decreased over time in the vaccinated
      birds compared to the unvaccinated control chickens. In spite of the phylogenetic
      distance between the NDV F gene inserted into the vector vaccine and the
      challenge virus (genotype I and V, respectively), the rHVT NDV vaccine provided
      good clinical protection and significantly reduced challenge virus shedding.

PMID- 22856184
TI  - Transmission and shedding patterns of Salmonella in naturally infected captive
      wild roof rats (Rattus rattus) from a Salmonella-contaminated layer farm.
AB  - Rodents play a major role in the transmission and maintenance of Salmonella
      contamination cycles in poultry facilities. However, very limited field data are
      available regarding the transmission routes, infection cycle, and shedding
      patterns of Salmonella by naturally infected wild rodents from commercial layer
      farms. In this study, a total of 128 resident wild roof rats (Rattus ratus) were
      captured from a Salmonella-contaminated layer facility. All roof rats were
      divided into 51 laboratory cages, and weekly monitoring of Salmonella fecal
      shedding patterns was conducted for 53 wk. Seven roof rats from cages that were
      observed to frequently shed Salmonella were isolated in individual cages, and
      daily Salmonella monitoring was performed for 35 days. At the end of monitoring,
      each roof rat was euthanatized, and isolation of Salmonella from different organs
      was performed. Results of weekly monitoring of Salmonella showed that 21 of 51
      cages (41.2%) were positive for Salmonella Infantis, while two cages (3.92%) were
      positive for Salmonella Enteritidis. Moreover, 11 cages were positive for
      Salmonella for at least two sampling weeks. Isolation of Salmonella from fecal
      droppings was mainly observed during the first 12 wk of captivity. The longest
      interval between two Salmonella-positive fecal dropping was 24 wk. In the daily
      Salmonella monitoring, only Salmonella Infantis was isolated from fecal
      droppings, in which the highest number of Salmonella Infantis organisms per fecal
      dropping was at 1 x 10(8) colony-forming units (cfu), while the lowest measured
      quantity was 1 x 10(3) cfu. It was noted that the frequency of Salmonella
      shedding in fecal droppings appeared to have a linear correlation (r = 0.85) with
      the number of Salmonella organisms (cfu) per fecal pellet (P < 0.05). Moreover,
      pulsed-field gel electrophoresis analysis of Salmonella Infantis isolates
      revealed a single identical pulsed-field pattern. Salmonella Enteritidis isolates
      from fecal droppings and internal organs also generated a single identical pulsed
      field pattern. Interestingly, Salmonella Infantis was not isolated from any of
      the organs examined, while Salmonella Enteritidis was isolated from the spleen
      and liver of one roof rat. These results may indicate that wild roof rats could
      persistently carry Salmonella and contaminate commercial poultry facilities
      through intermittent fecal shedding. Moreover, Salmonella Enteritidis in wild
      roof rats appears to be more of a systemic infection, in which isolation is most
      likely to occur in internal organs, whereas Salmonella Infantis is more likely an
      enteric type of infection, in which isolation is most likely to occur in the
      intestinal contents. It is very plausible that layer chickens could become
      infected with Salmonella through ingestion of Salmonella-positive fecal droppings
      or feeds contaminated with these fecal droppings from infected resident roof
      rats. This is likely one of the major reasons why layer houses can be
      persistently infected by Salmonella even if the facilities are thoroughly cleaned
      and disinfected and if replacement stocks are obtained from Salmonella-free
      breeders and rearing units. It is therefore a noteworthy suggestion that rodent
      control programs inside poultry premises comprise an essential and effective tool
      in the management and control of Salmonella contamination in layer flocks.

PMID- 22856185
TI  - Optimization of the protocols for double vaccination against Marek's disease by
      using commercially available vaccines: evaluation of protection, vaccine
      replication, and activation of T cells.
AB  - Revaccination against Marek's disease is a widespread practice in some countries.
      The rationale of this practice is unknown, and there is no consensus in the
      protocols. Recently, we have demonstrated that administration of the first
      vaccine at 18 days of embryonation followed by a more protective second vaccine
      at hatch (18ED/1d) reproduced systematically the benefits of revaccination under
      laboratory conditions. Here, we have used the same model to optimize the
      revaccination protocols by using currently available vaccines and to determine
      whether two features associated with Marek's disease vaccine-induced protection
      (activation of T cells and replication of vaccine virus) are involved in the
      revaccination protocols. Protection conferred by three revaccination protocols
      (turkey herpesvirus [HVT] 18ED/HVT+SB-1 1d, HVT 18ED/CVI988 1d, and HVT+SB-1
      18ED/ CVI988 1d) was evaluated. Revaccination protocols also were compared with
      single vaccination protocols (HVT 18ED, HVT+SB-1 18ED, HVT+SB-1 1d, CVI988 18ED,
      and CVI988 1d). Our results demonstrated that it is possible to improve efficacy
      of the currently available vaccines by using them in revaccination programs.
      Administration of HVT 18ED/CVI988 1d and HVT+SB-1 18ED/CVI988 1d were the two
      protocols that conferred the highest protection against a very early challenge (2
      days of age) with very virulent plus Marek's disease virus strain 648A. In a
      separate experiment, we evaluated vaccine replication and activation of T cells
      in single and revaccination protocols. Our results demonstrated that replication
      of the second vaccine, although decreased compared with single vaccination, could
      be detected at 3 days (HVT, CVI988) or at 6 days (SB-1). Administration of the
      first vaccine (HVT) at 18ED resulted in a high percentage of activated T cells.
      Administration of a second vaccine (either HVT-SB-1 or CVI988) at 1d resulted in
      increased intensity of MHC-II stain in activated T cells.

PMID- 22856186
TI  - Gel-Bead Delivery of Eimeria oocysts protects chickens against coccidiosis.
AB  - Vaccines composed of either virulent or attenuated Eimeria spp. oocysts have been
      developed as an alternative to medication of feed with ionophore drugs or
      synthetic chemicals. The purpose of this study was to evaluate the use of gel
      beads containing a mixture of Eimeria acervulina, Eimeria maxima, and Eimeria
      tenella oocysts as a vaccine against coccidiosis. Newly hatched chicks (Gallus
      gallus domesticus) were either sprayed with an aqueous suspension of Eimeria
      oocysts or were allowed to ingest feed containing Eimeria oocysts-incorporated
      gel-beads. Control day-old chicks were given an equivalent number of Eimeria
      oocysts (10(4) total) by oral gavage. After 3 days, chicks were randomly assigned
      to individual cages, and feces were collected between days 5 and 8 postinfection.
      All samples were processed for total Eimeria oocysts. At 4 wk of age, all
      chickens and a control nonimmunized group received a high-dose E acervulina, E
      maxima, and E. tenella challenge infection. Oocyst excretion by chicks fed gel
      beads or inoculated by oral gavage was 10- to 100-fold greater than that of
      chicks spray-vaccinated with the Eimeria oocysts mixture (log 6.3-6.6 vs. log
      4.8). Subsequent protection against challenge as measured by weight gain and feed
      conversion efficiency was significantly greater (P < 0.05) in gel-bead and oral
      gavage groups compared with spray-vaccinated or nonimmunized groups. Also, gel
      bead and oral gavage groups showed no significant difference (P > 0.05) in weight
      gain and feed conversion efficiency compared with nonchallenged controls. These
      findings indicate that incorporation of Eimeria spp. oocysts in gel-beads may
      represent an effective way to deliver live oocyst vaccines to day-old chicks for
      preventing subsequent outbreaks of coccidiosis in the field.

PMID- 22856187
TI  - Influence of swab material on the detection of Mycoplasma gallisepticum and
      Mycoplasma synoviae by real-time PCR.
AB  - Recent reports have shown an increased recovery of cells from flocked nylon swabs
      which may improve the specimen quality and the real sensitivity of diagnostic
      tests in a clinical setting. In this study, the detection of Mycoplasma
      gallisepticum (MG) and M. synoviae (MS), using dry swabs of different materials
      (nylon flocked, cotton, and polyester), was investigated using real-time TaqMan
      PCR protocols. Different types of samples, including dilutions of pure broth
      cultures of MG and MS as well as swabs from tracheas of experimentally infected
      chickens and field cases of infection, were analyzed. There were no statistical
      differences in real-time PCR results among the different swab types (P < 0.05),
      indicating that this is not likely to be a significant factor in MG and MS
      detection by this method.

PMID- 22856188
TI  - Development and preliminary application of a quantitative PCR assay for detecting
      gtxA-containing Gallibacterium species in chickens.
AB  - A quantitative PCR (qPCR) assay using SYBR Green I was developed based on the
      published sequence of the gtxA gene from Gallibacterium anatis. This method
      produced reliable specificity, sensitivity, and repeatability. The detection rate
      of Gallibacterium in 181 clinical samples was 36.5% (66/181) by qPCR, which was
      superior to the detection rate of Gallibacterium-specific PCR (0/181) and an
      isolation and identification assay (18.2% or 33/181). No association was found
      between the prevalence of Gallibacterium and the age of the chickens.
      Gallibacterium infection was detected in one 4-day-old chicken, showing that
      infection can occur much earlier than the previously stated fourth week of life.
      Tissue sample analysis showed that Gallibacterium is mainly located in the
      trachea and ovaries, based on results from three groups of chicken with different
      health statuses. Furthermore, a titer analysis suggested that Gallibacterium
      loads in different organs may correlate with different clinical manifestations of
      disease. Thus, the qPCR assay developed in the present study is useful for
      identification and quantitative analysis of gtxA-containing Gallibacterium in
      various tissue samples from birds and for the assessment of the pathogenic
      mechanisms of Gallibacterium.

PMID- 22856189
TI  - Complete genomic sequence of the virulent bacteriophage RAP44 of Riemerella
      anatipestifer.
AB  - A virulent Riemerella anatipestifer bacteriophage, RAP44, belonging to the
      Siphoviridae family of tailed phages, was previously isolated from feces of
      healthy Muscovy ducks in China. A complete genomic sequence analysis indicates
      that the phage's genome consists of a linear, double-stranded DNA molecule of
      49,329 nucleotides. Eighty open reading frames (ORF) were identified. Putative
      functions could be assigned to 24 of the ORFs. The location of these genes was
      consistent with organization of the genome in a modular format which includes
      modules for host cell lysis, tail morphogenesis, head morphogenesis, and DNA
      replication and modification modules. Until now, no R. anatipestifer phage genome
      sequence has been reported in the literature. Therefore, this study represents
      the first complete genomic and molecular description of the R. anatipestifer
      phage.

PMID- 22856191
TI  - Antibody response and viral shedding profile of Egyptian geese (Alopochen
      aegyptiacus) infected with low pathogenicity H7N1 and H6N8 avian influenza
      viruses.
AB  - Egyptian geese (Alopochen aegypticus), a duck species endemic to sub-Saharan
      Africa and occasionally implicated in the transmission of avian influenza viruses
      (AIV) to farmed ostriches, were experimentally infected with low pathogenicity
      H7N1 and H6N8 viruses to assess viral shedding and immune profiles. Following the
      first infection with H7N1 virus, high titers of virus were shed from both the
      tracheae and cloacae for at least 7 days postinfection, and tracheal shedding
      lasting until day 14. All detectable shedding from both tracheae and cloacae had
      ceased within 28 days of infection. Antibody titers peaked at day 7
      postinfection, but the initial immune response was short-lived. Birds that
      received a second challenge with the homologous H7N1 virus mounted a more robust
      response that lasted beyond 66 days postchallenge, and H7N1 virus was detected,
      albeit at much lower levels, until day 28 post secondary infection (psi) in the
      cloaca and beyond day 28 psi in the trachea. Birds that received an initial
      infection with H7N1 virus were also challenged with H6N8 virus, and because a
      comparable shedding pattern to the H7N1 challenge group was observed, we
      concluded that the effect of any nonspecific immunity was negligible.

PMID- 22856190
TI  - Selection of a recombinant Marek's disease virus in vivo through expression of
      the Marek's EcoRI-Q (Meq)-encoded oncoprotein: characterization of an rMd5-based
      mutant expressing the Meq of strain RB-1B.
AB  - Marek's disease (MD) is a highly contagious viral disease of chickens (Gallus
      gallus domesticus) caused by MD virus (MDV), characterized by paralysis,
      neurologic signs, and the rapid onset of T-cell lymphomas. MDV-induced T-cell
      transformation requires a basic leucine zipper protein called Marek's EcoRI-Q
      encoded protein (Meq). We have identified mutations in the coding sequence of Meq
      that correlated with virus pathotype (virulent, very virulent, and very virulent
      plus). The aim of this study was to determine whether recombinant viruses could
      be isolated based on Meq expression through in vivo selection. Chicken embryo
      fibroblasts (CEFs) were cotransfected with an rMd5 strain-based Meq deletion
      virus (rMd5deltaMeq) and meq loci from strains representing different pathotypes
      of MDV. Transfected CEFs were inoculated into chickens in two independent
      studies. We were able to isolate a single recombinant virus, rMDV-1137, in a
      contact-exposed chicken. rMDV-1137 had recombined two copies of the meq gene of
      RB-1B and was found to have pathogenicity similar to both RB-1B and rMd5 parental
      strains. We found the RB-1B- and rMd5-induced lymphomas showed differences in
      composition and that rMDV-1137-induced lymphomas were intermediate in their
      composition. We were able to establish cell lines from both RB-1B- (MDCC-UD35, 
      UD37) and rMDV-1137 (MDCC-UD36, -UD38)-induced, but not rMd5-induced, lymphomas.
      To date, no rMd5- or parent Md5-transformed T-cell lines have been reported. Our
      results suggest that 1) a recombinant MDV can be selected on the basis of
      oncogenicity; 2) changes in Meq sequence seem to affect tumor composition and the
      ability to establish cell lines; and 3) in addition to meq, other genomic loci
      affect MDV pathogenicity and oncogenicity.

PMID- 22856192
TI  - Immune response to liposome-associated recombinant SEF21 following oral
      immunization in chickens.
AB  - In order to generate Salmonella enterica serovar Enteritidis fimbriae antigens
      (rSEF21), the intact region encoding SEF21 was amplified from Salmonella
      Enteritidis by PCR and subcloned into a prokaryotic expression vector pET-28a(+)
      to yield pET-28a(+)-SEF21. The rSEF21 protein was highly expressed and purified
      by nickel affinity chromatography. Liposomeassociated rSEF21 was prepared for
      oral immunization to seek protective efficacy for intestinal infection with
      Salmonella Enteritidis. Evidence of IgA and IgG responses were found in the
      intestinal tracts and in the sera of a group of chickens immunized. Two weeks
      after the booster immunization, the chickens were challenged orally with 2 x
      10(6) colony-forming units of live Salmonella Enteritidis, and fecal samples were
      examined for bacterial excretion from the intestinal tract. Significantly less
      fecal excretion of bacteria was observed in immunized chickens for 4 wk after
      challenge. The numbers of bacteria in the intestinal contents (cecum and rectum)
      were also significantly lower in immunized chickens than in unimmunized controls.
      Therefore, oral immunization with liposome-associated rSEF21 elicits both
      systemic and mucosal antibody responses, leading to a reduction in bacterial
      colonization in the intestinal tract and excretion of Salmonella Enteritidis in
      the feces.

PMID- 22856193
TI  - Efficacy of soluble recombinant FliC protein from Salmonella enterica serovar
      enteritidis as a potential vaccine candidate against homologous challenge in
      chickens.
AB  - FliC, the flagellin antigen of Salmonella Enteritidis, was tested as a vaccine
      candidate for protective effect against a homologous challenge in chickens. After
      immunization with recombinant FliC (rFliC) or administration of phosphate
      buffered saline (PBS) at 56 days old, the chickens were challenged with 10(9)
      colony-forming units of Salmonella Enteritidis at 76 days old. The vaccinated
      birds showed significantly decreased bacterial counts in the liver and cecal
      contents compared to those administered PBS at 7 days postchallenge, but the
      protection was partial. The replication experiment also showed a similar result.
      In both experiments, vaccination induced an increased level of serum anti-rFliC
      IgG, which was also reactive to the native flagella. The intestinal IgA level was
      slightly higher in the vaccinated birds than in the control. However, neither the
      proliferative response nor interferon-gamma secretion of splenic cells upon
      stimulation with rFliC was induced. Therefore, the effect of rFliC as a vaccine
      is limited, and further improvement is needed.

PMID- 22856194
TI  - Serovar identification, antimicrobial sensitivity, and virulence of Avibacterium
      paragallinarum isolated from chickens in Thailand.
AB  - Avibacterium paragallinarum causes infectious coryza in chickens, an acute
      respiratory disease that has worldwide economic significance. The objectives of
      this study were to determine the serovars, antimicrobial resistance, and
      pathogenicity of A. paragallinarum isolated from chickens in Thailand. Eighteen
      field isolates of A. paragallinarum were confirmed by PCR. When examined by
      serotyping in a hemagglutination inhibition test, 10 isolates were serovar A,
      five isolates were serovar B, and three isolates were serovar C. The
      susceptibility of the isolates to 16 antimicrobial agents was tested by a disk
      diffusion method. All isolates were susceptible to amoxicillin-clavulanic acid.
      There was a high level of resistance to lincomycin and erythromycin. All isolates
      were resistant to cloxacillin and neomycin. A study of bacterial entry into, and
      survival within, chicken macrophages showed variation between isolates but no
      clear connection to serovar. A virulence test was performed by challenging 4-wk
      old layers via the nasal route with 400 dl of bacteria (10(8) colony-forming
      units/ml). Clinical signs were observed daily for 7 days, and the birds were
      subjected to a postmortem necropsy at 7 days postchallenge. All 18 field isolates
      caused the typical clinical signs of infectious coryza and could be re-isolated
      at 7 days after challenge. There was no significant difference in the clinical
      scores of the isolates except that two isolates (112179 and 102984, serovars A
      and B, respectively) gave a significantly higher score than did isolate CMU1009
      (a serovar A isolate). No correlation between serovar and severity of clinical
      signs was found.

PMID- 22856195
TI  - Improved broiler performance associated with Ornithobacterium rhinotracheale
      vaccination in breeders.
AB  - During a field study in 2010 the daily growth, feed conversion, first-week
      mortality, broiler loss due to mortality and slaughterhouse condemnation, and
      production index were monitored in 100 broiler flocks derived from four breeder
      farms vaccinated with Nobilis OR inac and four Ornithobacterium rhinotracheale
      unvaccinated breeder farms of the same organization in Belgium. Other parameters
      related to the broiler flocks, such as flock size, season, age of the breeders,
      and corresponding breeder farms, were also noted. All gathered data were examined
      with ANOVA, linear correlation, and linear regression analyses. Results
      demonstrated a significant 22.3% lower broiler loss and a significant 3.9% higher
      production index in the broiler flocks derived from breeders vaccinated with
      Nobilis OR inac. These results confirm field observations obtained in 1999,
      thereby providing further evidence for an effect of O. rhinotracheale vaccination
      in breeders with regard to the improved performance of broilers.

PMID- 22856196
TI  - Detection and differentiation of avian reoviruses using SYBR-Green I-based two
      step real-time reverse transcription PCR with melting curve analysis.
AB  - A two-step SYBR-Green I-based real-time PCR with melting curve analysis was
      developed to detect and differentiate the avian reovirus (ARV) sigmaC gene in
      field and vaccine ARVs. Three primer sets were used to amplify the sigmaC gene
      from its 5', center, and 3' regions and analyze the melting point temperatures of
      nine ARVs. By combining the melting curves of the three ARV sigmaC gene regions,
      melting curve analysis could accurately distinguish the ARVs of different
      subtypes, and the results were consistent with phylogenetic analysis. The ARV
      sigmaC gene polymorphisms from different strains were also used to explain the
      differences in melting point temperatures. Compared with traditional subtyping
      methods, the current melting curve analysis provided an accurate test for
      separating ARVs, thereby making it a useful method for the improved selection of
      ARV vaccines.

PMID- 22856197
TI  - Diagnostic sensitivity and specificity of a participatory disease surveillance
      method for highly pathogenic avian influenza in household chicken flocks in
      Indonesia.
AB  - A study was conducted to assess the diagnostic sensitivity and specificity of a
      disease surveillance method for diagnosis of highly pathogenic avian influenza
      (HPAI) outbreaks in household chicken flocks used by participatory disease
      surveillance (PDS) teams in Yogyakarta Province, Indonesia. The Government of
      Indonesia, in partnership with the Food and Agriculture Organization of the
      United Nations, has implemented a PDS method for the detection of HPAI outbreaks
      in poultry since 2006. The PDS method in Indonesia utilizes both a clinical case
      definition (CD) and the result of a commercial rapid antigen test kit Yogyakarta
      55611, to diagnose HPAI outbreaks, primarily in backyard chicken flocks. The
      following diagnostic sensitivities and specificities were obtained relative to
      real-time reverse transcription-PCR as the gold standard diagnostic test: 1) 89%
      sensitivity (CI95: 75%-97%) and 96% specificity (CI95: 89%-99%) for the PDS CD
      alone; 2) 86% sensitivity (CI95: 71%-95%) and 99% specificity (CI95: 94%-100%)
      for the rapid antigen test alone; and 3) 84% sensitivity (CI95: 68%-94%) and 100%
      specificity (CI95: 96%-100%) for the PDS CD result combined with the rapid
      antigen test result. Based on these results, HPAI outbreaks in extensively raised
      household chickens can be diagnosed with sufficient sensitivity and specificity
      using the PDS method as implemented in Indonesia. Subject to further field
      evaluation, data from this study suggest that the diagnostic sensitivity of the
      PDS method may be improved by expanding the PDS CD to include more possible
      clinical presentations of HPAI and by increasing the number of rapid antigen
      tests to three different birds with HPAI-compatible signs of same flock.

PMID- 22856198
TI  - Study of nebulization delivery of aerosolized fluorescent microspheres to the
      avian respiratory tract.
AB  - This study investigated the delivery of an aerosol of monodisperse microspheres
      to the respiratory tract of birds following aerosol exposure. Adult domestic
      pigeons (Columbia livia domestica, n = 5 birds per timed treatment) were exposed
      to an aerosol of fluorescent 1.0 microm diameter carboxylate microspheres for
      0.5, 1, 2, or 4 hr. During the aerosolization period, the birds were free
      standing in a plexiglass treatment chamber and the aerosol was delivered using a
      commercial nebulizer. Immediately following aerosol exposure, the birds were
      euthanatized and the carcasses were intravenously infused with a modified
      paraformaldehyde/gluteraldehyde fixative. Evaluation of microsphere distribution
      was performed using a stereoscopic microscope with an epifluorescent module. The
      results from this study revealed that the amount of aerosolized particles
      delivered using a commercial nebulizer was proportional to exposure periods.
      Aerosol exposure periods of 0.5 hr or 1 hr did not result in a readily observable
      distribution of 1.0 microm fluorescent microspheres to the cranial thoracic,
      caudal thoracic, or abdominal air sac membranes. This was partly attributed to
      the relatively low concentration of the individual monodisperse microspheres in
      the aerosolized suspension. The 2- and 4-hr exposure periods resulted in readily
      observable deposition of the 1.0 mirom fluorescent microspheres in the cranial
      thoracic, caudal thoracic, or abdominal air sac membranes, with the 4-hr exposure
      period resulting in the greatest number of particles on the membrane surfaces.
      For each of the exposure periods, there was individual animal variation regarding
      the distribution and relative number of spheres deposited. This study
      demonstrates the widespread deposition of particles that had an aerodynamic
      equivalent diameter of approximately 1 microm and provides a better understanding
      of particle deposition efficiency within the respiratory system following aerosol
      exposure in birds.

PMID- 22856199
TI  - An rRT-PCR assay to detect the matrix gene of a broad range of avian
      paramyxovirus serotype-1 strains.
AB  - The current U.S. Department of Agriculture (USDA)-validated real-time reverse
      transcription-polymerase chain reaction (rRT-PCR) assay designed to detect the
      matrix gene of avian paramyxovirus serotype-1 (APMV-1) is the primary screening
      assay used in the United States. It has previously been shown to be unable to
      consistently detect all members of class I APMV-1. Diagnostic testing relies on
      rRT-PCR to quickly detect APMV-1 in wild birds, backyard flocks, live bird
      markets, commercial poultry, and for export testing. Limitations of the current
      USDA assay have raised concerns about the potential for some strains of APMV-1 to
      remain undetected by the primary screening assay. Mismatches in the probe were
      shown to cause a loss in template binding efficiency, resulting in lack of
      detection by the assay. Here, we describe the development and analytical
      validation of a new rRT-PCR assay designed to target a highly conserved region of
      the matrix gene across a wide range of APMV-1 strains. Limit of detection testing
      revealed a 3 log10 decrease in sensitivity for one low-virulence strain when
      compared to the USDA validated assay. Conversely, the assay showed increased
      sensitivity for a class I isolate and two virulent strains of APMV-1 that were
      not detected by the USDA-validated assay. The new assay also demonstrated a high
      degree of specificity by the lack of detection of 43 non-APMV-1 viruses.

PMID- 22856200
TI  - A comparative study of live attenuated F strain-derived Mycoplasma gallisepticum
      vaccines.
AB  - Commercially available attenuated strains of Mycoplasma gallisepticum (MG) are
      commonly used within the layer industry to control MG-induced mycoplasmosis.
      Among these are two live MG vaccines derived from the moderately pathogenic MG
      "chick F" strain. In the present study, the commercially available F strain
      derivatives were compared for their ability to elicit seroconversion, persist in
      vivo, and protect against virulent MG-induced airsacculitis. In addition, a
      noncommercial laboratory-derived high-passage F strain isolate was included in
      the study. Commercial (Hy-Line W-36) layers were placed in biological isolation
      units at 9 wk of age (woa). At 10 woa, birds within each biological isolation
      unit were treated via eye-drop application with one of the three F strain-derived
      vaccines at one of four levels (1x, 10(-1)x, 10(-2)x, or 10(-3)x). For the
      commercially available F strain derivatives, 1x equaled the manufacturer's
      recommended dose. The 1x dose of the noncommercial laboratory-maintained F strain
      derivative equaled 20 microl of a 48 hr culture. For wk 1-6 postvaccination
      (p.v.), sera were collected weekly from each bird, and seroconversion was
      assessed via serum plate agglutination (SPA). Virulent MG (strain R(low))
      challenge occurred via intratracheal inoculation at 7 wk p.v. Necropsies were
      subsequently performed to assess challenge-associated airsacculitus. For each F
      strain derivative applied at 1x and 10(-1)x, 100% seroconversion, as measured by
      SPA, was demonstrated by 6 wk p.v., and rates at the 10(-2)x dosage were 10% and
      90% for the commercial vaccines and 60% for the laboratory-derived strain in this
      period. Following challenge, airsacculitis was observed in 66.67% of the
      nontreated controls but not in any 1x- or 10(-1)x-treated bird independent of
      applied F strain derivative.

PMID- 22856201
TI  - Evaluation of novel adjuvant Eimeria profilin complex on intestinal host immune
      responses against live E. acervulina challenge infection.
AB  - The effects against avian coccidiosis of two novel adjuvants, Quil
      A/cholesterol/dimethyl dioctadecyl ammonium bromide/Carbopol (QCDC) and QCDC/Bay
      R1005 (R)/cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (CpG ODN [T])
      (QCDCRT) emulsified with profilin, a conserved Eimeria recombinant protein, were
      determined in broiler chickens. Chickens were subcutaneously immunized with
      isotonic saline (control group), profilin (P), profilin emulsified with QCDC (P
      Q), or profilin with QCDCRT (P-QR) at 2 and 9 days post-hatch and orally
      challenged with 1.0 x 10(4) sporulated oocysts of Eimeria acervulina (EA) at 7
      days postimmunization. All profilin-immunized groups showed increased body weight
      gain when compared to the control group, and the P-QR group had significantly
      higher body weight gain than did those of the P and P-Q groups following EA
      challenge infection. All groups immunized with profilin showed significantly
      decreased intestinal lesions compared with the control group, with the P-QR group
      showing the lowest intestinal lesions among the profilin-treated groups. Finally,
      the P-QR group showed greater CD4+/CD8+ and TCR1+/TCR2+ splenocytes and higher
      antiprofilin serum antibody titers compared with the P and P-Q (or both) groups
      following EA challenge infection. These results further suggest that vaccination
      of chickens with profilin, in combination with the QCDCRT adjuvant, may provide a
      novel control strategy against EA infection in commercial flocks.

PMID- 22856202
TI  - Optimization of a duplex real-time PCR method for relative quantitation of
      infectious laryngotracheitis virus.
AB  - Infectious laryngotracheitis is a highly contagious respiratory disease of
      chickens controlled by biosecurity and vaccination with live attenuated or
      recombinant vaccines. Infectious laryngotracheitis virus (ILTV) infections are
      characterized by a peak of viral replication in the trachea followed by a steady
      decrease in replication that results in the establishment of latency. Estimation
      of viral load is an important tool to determine the stage of ILTV infection.
      Here, a multiplex real-time PCR was optimized for the quantification of ILTV
      genomes. Quantification of viral genomes was based on the amplification of the
      ILTV UL44 gene, and sample variability was normalized using the chicken
      (Gallusgallus domesticus) alpha2-collagen gene as an endogenous control in a
      duplex reaction.

PMID- 22856203
TI  - Serologic evidence of exposure of raptors to influenza A virus.
AB  - Serum or plasma samples from raptors that prey or scavenge upon aquatic birds
      were tested by a commercially available blocking enzyme-linked immunosorbent
      assay for the evidence of antibodies to influenza A virus. Samples were taken
      from birds (n = 616) admitted to two rehabilitation centers in the United States.
      In addition, samples from 472 migrating peregrine falcons (Falco peregrinus)
      trapped on autumnal and vernal migrations for banding purposes were also tested.
      Only bald eagles were notably seropositive (22/406). One each of peregrine
      falcon, great horned owl (Bubo virginianus), and Cooper's hawk (Accipiter
      cooperi) from a total of 472, 81, and 100, respectively, were also positive. None
      of the turkey vultures (n = 21) or black vultures (n = 8) was positive. No
      clinical signs referable to avian influenza were seen in any bird at the time of
      capture. These data indicate that, among raptors, bald eagles do have exposure to
      influenza A viruses.

PMID- 22856204
TI  - Identification of mixed infections with different genotypes of avian bornaviruses
      in psittacine birds with proventricular dilatation disease.
AB  - Proventricular dilatation disease (PDD) is a fatal, progressive neurological
      disorder of psittacine birds, which is caused by a single-stranded RNA virus, the
      avian bornavirus (ABV). The disease pattern includes lymphoplasmacytic
      inflammation of the central, peripheral and autonomic nervous system. Seven avian
      bornavirus genotypes have been identified during the last years. So far only
      monoinfections with a single genotype of ABV have been attributed to PDD cases.
      However, after a recent survey discovered a case of a double infection with two
      different ABV genotypes, this seemed to indicate the need for a more systematic
      search for mixed infections. Brain specimens from 21 psittacine birds affected
      with PDD were examined. Aim of the investigation was to generate partial ABV
      sequences of a part of the matrix protein (M) gene and to evaluate whether
      sequences of more than one ABV genotype were present. RNA was extracted, and
      subjected to reverse transcriptase PCR with primer pairs generating a partial
      sequence of the matrix protein (M) gene, followed by a cloning procedure. Ten
      clones per case were sequenced in order to elucidate whether sequences
      characteristic for one or more than one genotype were present. In 19 of 21 cases
      clear M gene sequences could be generated; in two cases nucleic acid
      amplification failed. Seven birds were infected with ABV 2 and nine with ABV 4,
      representing the predominant genotypes in Europe. Two cases showed a mixed
      infection with ABV 2 and ABV 4, and one case a mixed infection with ABV 2 and ABV
      6. These results suggest that the molecular cloning method is a useful tool for
      distinguishing between single and multiple infection events by different ABV
      genotypes.

PMID- 22856205
TI  - Downgrading of heavy broiler chicken carcasses due to myodegeneration of the
      anterior latissimus dorsi: pathologic and epidemiologic studies.
AB  - Recently, in some Brazilian poultry companies, a dorsal cranial muscular lesion
      has been increasingly detected in broilers, causing heavy economic losses due to
      carcass downgrading. The observed gross lesions located in the anterior
      latissimus dorsi (ALD) muscle are characterized by yellowish discoloration of the
      skin and swelling on the dorsal cranial region of that muscle. When the ALD
      muscle is cut, subcutaneous edema, muscular superficial hemorrhage, pallor,
      adherence, and increased thickness and density are observed. Microscopically,
      findings indicate degenerative and polyphasic features, variation in fiber size
      and splitting, presence of hyaline, necrotic and regenerative myofibers,
      extensive fibrosis, and adipose tissue with lymphohistiocytic infiltration in all
      ALD muscles affected. The etiology of the lesion is unknown, and no detailed
      report was found in literature. The highest frequency of carcass downgrading due
      to this lesion was found in the heaviest and the oldest males of high-yield
      broiler strains (P < 0.01). This study is the first to describe the pathologic
      and some epidemiologic aspects of this new myopathy.

PMID- 22856206
TI  - Primary bone tumors in birds: a review and description of two new cases.
AB  - Primary bone tumors are only occasionally reported in avian species. This paper
      presents the cases of an osteosarcoma in a 6-yr-old free-range chicken and a
      chondrosarcoma in a 3-yr-old barred Plymouth Rock chicken. The well
      differentiated, moderately productive osteoblastic osteosarcoma arose from the
      synsacral vertebrae and had metastasized to the liver. The chondrosarcoma was
      well differentiated and firmly attached to the left side of the keel. There was
      no evidence of metastasis.

PMID- 22856207
TI  - A case of unilateral periorbital cellulitis and mandibular osteomyelitis in a
      turkey flock.
AB  - A farm of meat turkeys was affected by a condition, clinically characterized by
      unilateral inflammation of the orbital region and progressive crossing of the
      beak, observed in three successive flocks in 2010. While no toxic, genetic,
      technical, or diet causes could be found, pathologic and bacteriologic analyses
      were conducted to investigate the case. Pathologic analyses of the heads of
      affected birds showed blepharitis and exudative sinusitis as well as severe
      chronic osteomyelitis of all skull bones and mandibula. Staphylococcus aureus was
      consistently isolated from these lesions. It is supposed that the severe
      bacterial osteomyelitis induced deviation of some bones, thereby leading to
      deviation of the beak. Further investigations remain to be carried out to explain
      these successive outbreaks of staphylococcal osteomyelitis in skull bones.

PMID- 22856208
TI  - Prevalence of pigeon circovirus infections in feral pigeons in Ljubljana,
      Slovenia.
AB  - Pigeon circovirus (PiCV) was detected by real-time PCR in cloacal swabs,
      pharyngeal swabs, and serum samples taken from 74 feral pigeons (Columba livia
      var. domestica) that were caught at various locations in the city of Ljubljana,
      Slovenia. PiCV infections were detected in the majority of the tested birds. The
      highest (74.3%) detection rate was observed in the cloacal swabs and the lowest
      (31.1%) in serum samples. PiCV DNA was more readily detected in the cloacal
      swabs, pharyngeal swabs, and serum samples of birds younger than 1 yr. Molecular
      analysis of partial open reading frame V1 sequences showed that PiCV strains
      detected in feral pigeons share high nucleotide and amino acid sequence
      identities with PiCV strains detected in ornamental, racing, meat, and feral
      pigeons.

PMID- 22856209
TI  - Characterization of extraintestinal Escherichia coli isolated from a peacock
      (Pavo cristatus) with colisepticemia.
AB  - Extraintestinal infections by avian pathogenic strains of Escherichia coli (APEC)
      are commonly reported in poultry, but there is little information on infections
      by APEC in other bird species. Here we report on the characterization of
      extraintestinal E. coli isolated from a domesticated peacock, from the south of
      Brazil, that died of colisepticemia. Necropsy examination revealed congested
      liver, hypertrophied kidneys, peritonitis, severe typhlitis suggestive of
      coligranuloma, pneumonia, and airsacculitis--typical signs of colisepticemia. The
      isolates from lungs, kidney, heart, intestine, liver, and bone marrow all
      harbored the same virulence-associated factors (iucD, colV, iss, mat, fimC, ompA,
      traT crl, csgA vgrG, and hcp), yielded the same band pattern in amplified
      ribosomal DNA restriction analysis, and were allocated to the Escherichia coli
      Reference Collection group B1. The isolates were resistant to bacitracin,
      trimethoprim, and tetracycline, but displayed slight differences in their
      resistance to other antimicrobials. The isolates also differed in their virulence
      in 1-day-old chickens, but none displayed high virulence in vivo. We conclude
      that the peacock died of colisepticemia after it was infected with an
      extraintestinal E. coli strain of low virulence that nevertheless harbored
      virulence factors generally associated with APEC. This study represents the first
      characterization of an APEC isolated from a nonpoultry bird species.

PMID- 22856210
TI  - Trichomonosis in free-ranging Eurasian collared doves (Streptopelia decaocto) and
      African collared dove hybrids (Streptopelia risoria) in the Caribbean and
      description of ITS-1 region genotypes.
AB  - We report the first documented occurrence of an outbreak of trichomonosis in a
      free-ranging small flock of Eurasian collared doves (Streptopelia decaocto) and
      African collared dove hybrids (Streptopelia risoria) in the Caribbean. In total,
      18 birds were examined, including six African collared dove x Eurasian collared
      dove hybrids and 12 Eurasian collared doves. The affected age class consisted of
      adults. Sex distribution was equal. With a flock population size of 200 birds,
      mortality rate for the outbreak was estimated at 15-20%. Living birds were weak,
      showing evidence of mucus-stained beaks and open-mouth breathing. Caseous
      ulcerative yellow lesions were restricted to the upper gastrointestinal tract,
      with the exception of one bird, which had lesions in the upper gastrointestinal
      tract and in the liver. Ninety-four percent (17/18) of the affected birds had
      multiple extensive lesions. Lesions located on the roof of the oral cavity
      extended in 33% (6/18) into the orbit and in 11% (2/18) into the braincase. Using
      wet-mount microscopy, we were able to confirm Trichomonas gallinae in 22% (4/18)
      of the sampled animals. Fifteen samples submitted for PCR analysis tested
      positive. Sequence analysis of the internal transcribed spacer 1 (ITS-1) region
      of the ribosomal RNA (rRNA) revealed two distinct genotypes of Trichomonas. One
      sequence had 100% identity to the prototype T. gallinae isolate, whereas the
      other sequences had 98-100% identity to recently described Trichomonas-like
      parabasalid. On the basis of gross and histologic findings, along with the
      sequence results from the columbids in this report, it is likely that this
      Trichomonas-like parabasalid is pathogenic.

PMID- 22856211
TI  - If this is where we are in nursing, is this where we want to be?
AB  - I realize this incident was a decision made by one Nurse Leader. However, I see
      an inappropriate and, yes, unethical focus upon leadership. Two classic articles
      support my concern. Meindl and Ehrlich (1987) argue that romantization of
      leadership negatively impacts collective efforts to understand and improve
      organizations. Hall (2002) challenged that systems do not make mistakes, people
      do. She does not advocate blaming people; her point is that people make errors
      that kill patients but fixing the systems without 'fixing' people won't work.
      Both systems and people make mistakes. When I study current popular leadership
      theories and models, I see an 'if - then' format. For example, if and only if the
      Transformational Leader enacts specific behaviors, then RNs will act like adults,
      come to work, and do their job. I love nursing. I truly am saddened to see the
      direction the profession is taking. We are refusing to give staff RNs the gift of
      being professionals. This is where we are, is this where we want to be?

PMID- 22856212
TI  - Evidence-based practice: a basis challenge for nurse educators?

PMID- 22856213
TI  - Professional guides: bridging the gap between student and professional an
      assessment and challenge.
AB  - Orientation and socialization of new nurses is both a time intensive and costly
      endeavor. Positive mentorship experiences during instruction are crucial to
      optimum development and growth of expert nurses. Research has shown an increase
      in the attrition rate for new graduate nurses (Mills & Mullins, 2008, Ali &
      Pantaer, 2008). The attrition rate is attributed to the lack of adequate
      mentorship by professional nurses to new registered nurses as they transition
      from the student to professional role. The expenditure to hire, train, and orient
      a new registered nurse is equivalent to a registered nurse earned income of one
      year (Mills & Mullins, 2008). In order to combat some of these issues, attention
      must be directed at supporting the nursing student during nursing school and
      facilitating a smooth transition for the student entering the nursing profession.
      A program has been developed to ease the transition from student to professional
      which commences during the nursing student's junior year and progresses to
      graduation. This preliminary exposure to a structured mentorship program during
      nursing school provides the nursing student the opportunity to experience and
      utilize their mentor to smooth the transition from nursing student to registered
      nurse.

PMID- 22856214
TI  - Addressing moral distress: challenge and strategies for nursing faculty.

PMID- 22856215
TI  - Maternal genetic legacy of the eastern Adriatic island of Krk--an interplay of
      evolutionary forces and island's historical events in shaping the genetic
      structure of contemporary island population.
AB  - This study presents genetic diversity and structure of contemporary Krk islanders
      revealed by high-resolution mitochondrial DNA analysis on a sample of 132
      unrelated autochthonous adults from seven different settlements and regions of
      the island. Relatively high level of haplogroup and haplotype diversity in the
      overall island sample is an indicator of numerous migrations and gene flows
      throughout the history. Expectedly, the results show the highest frequency of
      haplogroup H (33.3%), yet this value is much lower compared to different Croatian
      and other European mainland populations. An interesting finding refers to highly
      elevated frequencies of some haplogroups, otherwise rare in Croatia and most of
      the Europe, such as I (11.3%) and W (7.6%) in Krk population, especially
      pronounced in some settlements. At the level of settlements, many of the major
      European haplogroups were found to be absent from their mtDNA gene pools, whereas
      several others show a pronounced deviation from an average. Overall, our results
      suggest a tangled interplay of different evolutionary forces, such as founder
      effects and a few strong bottlenecks, presumably due to epidemics, which have
      occurred in various periods of the island's history. Cultural customs, such as
      frequent endogamy in some regions of the island during past centuries, have
      additionally shaped its genetic structure into the observed present-day diversity
      patterns.

PMID- 22856216
TI  - Body mass index, waist circumference and waist-to-hip ratio: which anthropometric
      indicator is better predictor for the hypertension development in women
      population of the island Cres.
AB  - The aim of this research was to investigate the prevalence of obesity and high
      blood pressure and to prove which of three anthropometric indicators of obesity -
      waist circumference, body mass index (BMI) waist-to-hip ratio - is better
      predictor for the development of hypertension in women population of the island
      of Cres. We approached separately groups of women with measured high blood
      pressure and with previously diagnosed. The research was preformed within the
      research project "Genetic and biomedical characteristics of the population of the
      island of Cres". This was the cross sectional study and data were obtained on the
      sample of 247 females over 18 years old that voluntarily participated in this
      study. In our study group the prevalence of overweight was 39.0%, obesity 27.5%,
      increased waist circumference was present in 69.4% while increased blood pressure
      was found in 53.0% examinees. Our results indicate that age, BMI, impaired
      glucose concentration and serum cholesterol could be considered as predictors for
      the development of arterial hypertension, whether measured or previously
      diagnosed.

PMID- 22856217
TI  - A pilot Croatian survey of risk factor (CRO-SURF) management in patients with
      cardiovascular disease.
AB  - A pilot survey was performed to determine the presence of known risk factors for
      cardiovascular disease in Croatian patients with diagnosed coronary heart disease
      (CHD) using a new questionnaire. The idea was to test this new and very simple
      questionnaire but also to compare the data collected in this pilot survey with
      the results of the last Croatian national survey (TASPIC-CRO V) and so to obtain
      the information whether secondary prevention has improved between 2003 and 2010.
      122 patients with established CHD (88 men, 34 women, mean age 66.3 years) treated
      in Zagreb University Hospital Center were included. Data collection was based on
      filling the SURF questionnaire right after the clinical exam or later using
      review of medical records. Patients were hospitalized because of CABG (1%), PCI
      (8%), ACS (35%) or chronic stable angina (56%). The history of arterial
      hypertension had 95%patients (however, on admission mean systolic pressure was
      130.1 mmHg, diastolic 76.8 mmHg), 90% had dyslipidaemia (total cholesterol <4.5
      mmol/L had 43%; <4.0 mmol/L 33%; LDL-cholesterol <2.5 mmol/L 49%; <2.0 mmol/L
      32%; HDL>1.2 mmol/L (women) or >1.0 mmol/L (men) had 67%), 25% had diabetes which
      was poorly regulated (mean HbA1c 8.2%), 18% were active smokers. After discharge
      only 24% performed cardiac rehabilitation. Mean body mass index of the patients
      was 28.3 kg/m2 (32% were obese, 72% overweight). Compared to TASPIC-CRO V there
      was lower usage of aspirin than recommended on discharge. This was also true for
      statin therapy. More patients were taking beta blockers, calcium antagonists and
      diuretics than 7 years ago. This pilot survey showed that CRO-SURF questionnaire
      is short, quick, effective and simple to use. It is a good and cost effective
      tool to collect data on CVD risk factors and their management. The results
      obtained by using it indicate that there is still a high prevalence of modifiable
      risk factors in Croatian patients with CHD.

PMID- 22856218
TI  - Increase in specific density of levobupivacaine and fentanyl solution ensures
      lower incidence of inadequate block.
AB  - The clinical presentation of a subarachnoid block (SAB) is dependent upon the
      intrathecal spread of local anesthetic (LA). Intrathecal distribution depends on
      the chemical and physical characteristics of LA, puncture site, technique used,
      patient anatomical characteristics and hydrodynamic properties of cerebrospinal
      fluid. We tried to determine whether a combined glucose/LA solution can render a
      clinically significant difference in sensory block distribution and motor block
      intensity.This was a controlled, randomized and double blinded study. The
      surgical procedures were stripping of the great or small saphenous vein and
      extirpation of remaining varicose veins. The study included 110 patients
      distributed into two groups: Hyperbaric (7.5 mg levobupivacaine (1.5 ml 0.5%
      Chirocaine) + 50 microg Fentanyl (0.5 ml Fentanil) and 1 ml 10% glucose (Pliva))
      vs. Hypobaric (7.5 mg levobupivacaine (1.5 ml 0.5% Chirocaine) + 50 microg
      Fentanyl (0.5 ml Fentanil) and 1 ml 0.9% NaCl (Pliva, Zagreb)) adding to a total
      volume of 3.5 ml per solution. Spinal puncture was at L3-L4 level. Spinal block
      distribution was assessed in five minute intervals and intensity of motor block
      was assessed according to the modified Bromage scale. Pain was assessed with the
      Visual Analogue Scale. A statistically significant difference in sensory block
      distribution, motor block intensity and recovery time was established between
      hyperbaric and hypobaric solutions. By increasing the specific density of
      anesthetic solution, a higher sensory block, with lesser variability, a
      diminished influence of Body Mass Index, decreased motor block intensity and
      faster recovery time may be achieved.

PMID- 22856219
TI  - The relationship between prolonged cerebral oxygen desaturation and postoperative
      outcome in patients undergoing coronary artery bypass grafting.
AB  - 58 patients who underwent on-pump coronary artery bypass graft surgery were
      evaluated for changes in regional cerebral oxygen saturation (rSO2) measured by
      near infrared spectroscopy (NIRS). If rSO2 during the operation fell to more than
      20% under the baseline, standardized interventions were undertaken to maintain
      rSO2. Despite those interventions, in some cases we observed inability to
      maintain rSO2 above this threshold. Therefore we divided patients in two
      subgroups: 1. without prolonged rSO2 desaturation; 2. with prolonged rSO2
      desaturation (area under the curve >150 min% for rSO2<20% of baseline and >50
      min% for rSO2<50% of absolute value). The data were analyzed to determine whether
      there were major differences in outcome of these two groups. 18 out of 58
      patients (31%) had prolonged rSO2 desaturation during operation. There was
      significantly higher number of diabetic patients in group with prolonged rSO2
      desaturation (p=0.02). Intraoperative data revealed significantly more blood
      consumption during cardiopulmonary bypass (p=0.007) and the need for inotropes
      (p=0.04) in desaturation group. Three patients in prolonged desaturation group
      and no one in another group had stroke, coma or stupor (p=0.03). Logistic
      regression analysis revealed diabetes mellitus and age as predictors for
      prolonged rSO2 desaturation. We concluded that prolonged intraoperative rSO2
      desaturation is significantly associated with worse neurological outcome in
      patients - nonresponders to standardized interventions for prevention of rSO2
      desaturation.

PMID- 22856220
TI  - Dermatoglyphics in patients with hypothyreosis.
AB  - About 15% of all females and 3% of all males suffers from hypothyreosis. The
      thyroid disease is the most frequent cause of hypothyreosis, and among people in
      Croatia who are suffering from that disease 90% have been affected by its
      autoimmune form. The thyroid diseases are supposed to be caused by the influence
      of various genetic and external factors and some forms of genetic influences have
      not yet been studied. Analysis of digito-palmar dermatoglyphics has been used in
      the research of the role of genetic predisposition in many various diseases. We
      have analyzed correlation of qualitative and quantitative traits between the
      group of 50 females suffering from hypothyreosis and a control group of 100
      phenotypically healthy females. Quantitative statistical analysis using t-test
      has indicated only few significantly different variables, while the discriminant
      analysis has shown 76.9% correctly classified samples. The factor analysis has
      shown a high percentage of total variance within patients suffering from
      hypothyreosis, as well as the different structure of individual factors.
      Qualitative analysis has shown the heterogeneity between the two examined groups.
      The results of the research have proved that the qualitative characteristics are
      more unstable than the quantitative ones and they have also shown the instability
      of genes taking part in hypothyreosis development implying genetic predisposition
      of the disease.

PMID- 22856221
TI  - The influence of clinical and anthropometric parameters on the serum levels of
      the endothelin-1 in pregnant women and their newborns.
AB  - Pregnancy induced hypertension (PIH) is major contributor to maternal death in
      developing countries. Endothelin-1 (ET-1) is the most potent vasoconstriction
      agent known and its serum levels are increased in PIH. Therefore it is important
      to elucidate maternal and neonatal factors which influence endothelin-1 serum
      levels. 100 pathological pregnancies and 88 controls were analyzed for blood
      endothelin-1 and their anthropometric and clinical data were collected. In
      maternal blood ET-1 levels were strongly predicted by diagnosis, therapy and BMI,
      while umbilical cord ET-1 levels were strongly predicted by gestational age,
      therapy and delivery termination. Positive correlation between BMI and ET-1
      levels suggest that obese pregnant women have increased risk for cardiovascular
      diseases. Inverse relationship between Apgar and umbilical ET-1 indicates that ET
      1 could be considered as a prognostic marker in cases of neonatal asphyxia.

PMID- 22856222
TI  - Value of rapid aetiological diagnosis in optimization of antimicrobial treatment
      in bacterial community acquired pneumonia.
AB  - In 80 adult patients with community acquired pneumonia (CAP) conventional
      microbiological methods, polymerase chain reaction (PCR) and serum C-reactive
      protein (CRP) levels were performed and the appropriateness of the empirical
      antimicrobial treatment was evaluated according to bacterial pathogen detected.
      The aetiology was determined in 42 (52.5%) patients, with Streptococcus
      pneumoniae as the most common pathogen. PCR applied to bronchoalveolar lavage
      (BAL) provided 2 and PCR on sputum samples 1 additional aetiological diagnosis of
      CAP The mean CRP values in the S. pneumoniae group were not significantly higher
      than in the group with other aetiological diagnoses (166.89 mg/L vs. 160.11 mg/L,
      p = 0.457). In 23.8% (10/42) of patients with determined aetiology, the empirical
      antimicrobial treatment was inappropriate. PCR tests need further investigation,
      particularly those for the atypical pathogens, as they are predominant in
      inappropriately treated patients. Our results do not support the use of CRP as a
      rapid test to guide the antimicrobial treatment in patients with CAP.

PMID- 22856223
TI  - Tetrahydrophthalazine derivative "sodium nucleinate" exert its anti-inflammatory
      effects through inhibition of oxidative burst in human monocytes.
AB  - We described the use of a new chemical substance Sodium nucleinate (SN) as an
      immunomodulatory substance exhibiting antiinflammatory properties. Sodium
      nucleinate (SN) registrated in Russian Federation as Tamerit, is 2-amino-1,2,3,4
      tetrahydrophthalazine-1,4-dione sodium salt dihydrate, derivative of well known
      chemical substance luminol. To comprehend the mechanisms of SN immunomodulatory
      activity, we examined the SN modulation of the oxidative burst responses of whole
      blood human monocytes and polimorphonuclear cells (PMC) stimulated with phorbol
      12-myristate 13-acetate (PMA) or E. coli suspension in vitro. SN did not inhibit
      the proportion of neutrophils and monocytes phagocytosing E. coli. Oxidative
      burst responses of monocytes stimulated with PMA were strongly inhibited at SN
      concentration ranging from 10-500 mg/ml, less efficient inhibitor was SN in E.
      coli stimulated monocytes (inhibition range was from 50-500 mg/ml SN). SN
      inhibited PMC oxidative burst only in range 100-500 mg/ml SN. In conclusion, we
      found SN as an efficient inhibitor of oxidative burst in monocytes. Since ROS
      generation in monocytes/macrophages has been found to be important for LPS-driven
      production of several proinflammatory cytokines, SN may exsert its
      antiinflammatory effects through monocyte/macrophage oxidative burst inhibition.

PMID- 22856224
TI  - Correlation of endothelin-1 concentration and angiotensin-converting enzyme
      activity with the staging of liver fibrosis.
AB  - Increased serum angiotensin-converting enzyme (SACE) activity and serum
      concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We
      investigated a correlation between the different stages of liver fibrosis and
      SACE activity and serum ET-1 concentration. Seventy patients with
      pathohistologically established chronic liver disease were divided in three
      groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak
      score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak
      score 6, n=30). SACE activity and ET-1 concentration were determined using
      commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to
      the severity of disease, the highest being in patients with liver cirrhosis.
      Maximal increase in SACE activity was found between minimal and medium fibrosis
      while maximal increase in ET-1 concentration was revealed between medium fibrosis
      and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve
      for SACE activity suggested a cut-off value to separate minimal from medium
      fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value
      for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4
      pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE
      activity and ET-1 concentration was registered (Spearman's n = 0.438, p = 0.004).
      Both SACE activity and ET-1 concentration were increased in all stages of liver
      fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a
      biochemical marker for the progression of fibrosis. Positive correlation between
      SACE activity and ET-1 concentration might indicate their interaction in the
      development of liver cirrhosis.

PMID- 22856225
TI  - Rectal cancer treatment and survival--comparison of two 5-year time intervals.
AB  - In last two decades there was a huge step forward concerning rectal cancer
      treatment. The aim of our study was comparison of two time intervals regarding
      the methods of treatment and results of radical rectal cancer surgery. 407
      patients operated on for rectal cancer were included in study. Those were
      patients with elective radical resection of solitary rectal tumor who survived
      first month after the operation. Patients were divided in two groups regarding
      the time of operation. In group one were patients operated on between 1996 and
      2000 and in group two patients operated on between 2001 and 2005. We compared our
      results in both intervals with special interest about type of operation
      considering localization of the tumor, local recurrence and cancer related
      survival. Significant differences were found between two groups. There were more
      sphincter saving operations in second group, less local recurrences and better
      survival than in first group. This study observed significant improvements at
      recurrence rates and total survival for patients operated on rectal cancer.

PMID- 22856226
TI  - Detection of ovarian cancer by determination of CA 125 in different
      patohistologycal types of tumor according to age.
AB  - During the eighteen-year period in "Sestre milosrdnice" University Hospital
      Center, Zagreb, 271 women with ovarian tumor was studied. 229 women with ovarian
      cancer and 42 with borderline tumor. The pathohistological types of tumors were
      different. The age of the patients ranged from 20-83 years. In all patients the
      value of biochemical marker CA125 was determined. The aim of this study was to
      determine the usefulness of CA125 measurement in different age groups and in
      different patohistologycal forms of tumor. CA125 has proven to be positive in
      89.1% of women with ovarian cancer and in 62% with neoplasm of low malignant
      potential. The higher values of CA125 were detected in younger women with low
      malignant tumor potential. Serous and metastatic tumor types were also associated
      with higher values of CA125.

PMID- 22856227
TI  - Does life along the sea carry greater risk of thyroid cancer?
AB  - Aim of this study was to determine whether there are any differences between
      coastal and inland Dalmatia in incidence rates and clinical characteristics of
      thyroid cancer. Data on 651 persons who suffer from and have undergone surgery
      for thyroid cancer have been analysed. All patients lived in Dalmatia between
      1997 and 2006. Data were collected via surveys, insight into medical histories
      and results of histopathological analysis. In Dalmatia, in the overall sample,
      there are no statistically significant differences in incidence between coastal
      and inland areas (chi2=3.03; df=1; p=0.082). Somewhat higher overall incidence
      has been recorded in the inland (8.5%000) than in the coastal Dalmatia (7.3%000).
      In the overall sample, in Dalmatia, women make up 81.4% of patients and papillary
      cancer accounts for 80.0% of all thyroid cancers. The ratio of papillary to
      folicullar cancer is 7.8:1 in coastal and 4.2:1 in inland Dalmatia. Papillary and
      medullary types are more common in the coastal area and follicular and anaplastic
      cancer types in the inland area and the differences are statistically significant
      (p>0.033). Epidemiological characteristics of thyroid cancer in coastal Dalmatia
      are in accordance with the characteristics of this cancer as described in iodine
      sufficient areas: the most common type is papillary cancer, and the ratio of
      papillary to follicular is 7.8:1. Sex-wise, the coastal area records a higher
      ratio of male patients (1:3.8) than the inland area (1:7.1). There are no
      statistically significant differences in thyroid cancer incidence rates between
      coastal and inland Dalmatia. Epidemiological characteristics of thyroid cancer in
      inland Dalmatia are in some ways more similar to those of continental Croatia.
      This result could be the consequence of previous iodine insufficiency in inland
      Dalmatia.

PMID- 22856228
TI  - Macular thickness and volume parameters measured using optical coherence
      tomography (OCT) for evaluation of glaucoma patients.
AB  - The aim of this study was to evaluate macular thickness parameters in glaucoma
      patients and to compare them to normal subjects using Optical Coherence
      Tomography (OCT). This prospective, observational study included 20 primary open
      angle glaucoma patients (POAG) and 20 healthy subjects in control group.
      Exclusion criteria were diabetes and other macular pathology, like age-related
      macular degeneration, macular oedema, central serous retinopathy and high myopia
      >4.00 dsph. OCT imaging of peripapillar retina and macular area were performed
      using Cirrus HD OCT In these two groups of patients we analyzed changes of
      macular thickness parameters (central subfield thickness, macular volume, and
      average macular thickness). The group of glaucoma patients had decreased values
      of the two macular thickness parameters: macular volume and average macular
      thickness, compared to control group. There was no difference in central macular
      thickness, presumably because of the absence of the ganglion cells in this layer.
      Macular imaging can be a useful additional method to determine glaucoma status
      and has a potential for tracking glaucoma progression.

PMID- 22856229
TI  - Modified operative technique for involutional lower lid entropion.
AB  - The paper presents a modified operative technique for involutional lower lid
      entropion. The prospective noncomparative study of 101 lower eyelids of 88
      patients undergoing surgery for involutional lower lid entropion was conducted in
      period from September 2005 until March 2012. Indication for the surgery was
      entropion, previously untreated, with moderate to severe horizontal lid laxity
      and no clinically relevant medial and lateral canthal tendon laxity. The
      operative technique is our modification of Quickert and Jones procedures. Photo
      was taken preoperatively and one month after surgery. Clinical follow-up was at
      7th postoperative day, one month and six months after surgery and in case of the
      recurrence. Long-term follow-up was obtained via telephone interviews. There were
      44 male (50%) and 44 female (50%) patients included in the study. The age of
      patients was in average 73.27 +/- 8.1 years (range 53-90 years). Early
      postoperative complication was localized lid swelling found in two patients
      starting 4-6 weeks postoperatively at the area of absorbable suture. It resolved
      spontaneously in two and three weeks respectively. There was recurrence of
      entropion in 11 eyelids (10.89%) of 10 patients. The mean interval between
      primary surgery and the recurrence was 17.45 +/- 14.84 months (range 4-48
      months). In these eyelids Jones procedure was performed. However in four eyelids
      of four patients from the recurrent group an additional surgery needed to be
      performed after 6, 12, 12 and 17 months respectively. Our modification of
      surgical treatment for involutional lower lid entropion was effective in 89.11%
      of eyelids. Complications of the procedure were scarce.

PMID- 22856230
TI  - Polymorphisms of vitamin D receptor gene in the population of eastern Croatia
      with psoriasis vulgaris and diabetes mellitus.
AB  - The aim of this study was to evaluate the possible association between
      polymorphisms in the Vitamin D receptor gene (VDR gene) and tendency for
      development of psoriasis vulgaris and diabetes mellitus in the population of
      Slavonia, which is a region in the Eastern Croatia. In order to conduct the
      mentioned evaluation the restriction fragment length polymorphisms (ApaI, BsmI
      and TaqI) in the Vitamin D receptor gene were researched in three groups of
      patients: patients suffering only from psoriasis vulgaris, patients suffering
      only from diabetes mellitus, and patients suffering at the same time from both
      diseases. Four most common genotypes were found in all standardized control
      patients: triple heterozygotes BbAaTt (in 29.3% of the studied patients), bbAaTT
      (in 18.6% of the studied patients), bbaaTT (in 12.9% of the studied patients) and
      BbAATt (in 8.6% of the studied patients). Three most common VDR 3'-RFLP
      haplotypes determined in this study were: three-component baT, Bat and bAT
      haplotype. Results of the Hardy-Weinberg equilibrium showed presence of BsmI
      polymorphism genotype frequencies disequilibrium in the group of patients
      suffering from psoriasis and ApaI polymorphism in the group of patients suffering
      from both diseases. According to the same statistical test all conditions for
      TaqI polymorphism genotype frequency were fulfilled in all groups of studied
      patients. There was no significant difference in distribution of BsmI, ApaI or
      TaqI polymorphism genotype frequencies between control patients and any of the
      subgroup of studied patients. In studied population none of analysed
      polymorphisms individually was associated with the risk of development of
      psoriasis, diabetes or combined phenotype.

PMID- 22856231
TI  - Estimated glucose disposal rate in assessment of renal function in patients with
      type 1 diabetes.
AB  - Insulin resistance has been documented in type 1 diabetes and may contribute to
      the high risk for cardiovascular disease in this population and progression of
      nephropathy. We investigated associations of renal parameters, including urinary
      albumin excretion rate (UAE), serum creatinine and creatinine clearance, with
      surrogate measure of insulin sensitivity calculated using a formula derived from
      euglycemic-hyperinsulinemic clamp studies (estimated glucose disposal rate,
      eGDR). Study included 353 patients with type 1 diabetes, none showed signs of
      adrenal, thyroid, renal, or cardiovascular diseases. Insulin sensitivity was
      measured with eGDR calculated with the equation: 24.31-(12.22xWHR)-(3.29xHT)
      (0.57xHbA1c). The units were mgkg(-1)min(-1); WHR=waist to hip ratio;
      HT=hypertension. Correlations and logistic regression analysis were performed to
      identify relationships between renal parameters and eGDR, individual components
      of insulin resistance and risk of insulin resistance. UAE and serum creatinine
      significantly correlated with insulin resistance measured by eGDR (r=-0.13, and 
      0.17, all p<0.05), and its components disorders, WHR and HbA1c. After stratifying
      patients in quartiles of eGDR, those in the upper quartile of the eGDR had
      significantly reduced levels of UAE and serum creatinine, compared to subjects in
      lowest quartile. In a logistic regression analysis risk for development of
      insulin resistance in our subjects were independently predicted only by UAE (odds
      ratio = 1.01, p<0.01). Our results provide evidence of associations between
      insulin resistance and its components disorders with renal parameters, such as
      UAE and serum creatinine. Insulin resistance, measured with eGDR, predicts the
      increment in UAE in subjects with type 1 diabetes. Since progression to
      microalbuminuria is likely to occur in majority of diabetic patients, there is a
      need to further explore the role of risk factors such as insulin resistance.

PMID- 22856232
TI  - Relationship between psychopathological factors and metabolic control in children
      and adolescents with insulin-dependent diabetes mellitus.
AB  - This paper provides a critical overview of the literature on the relationship
      between psychological/psychopathological factors and metabolic control in
      children and adolescents with insulin dependent diabetes mellitus (IDDM). We
      discuss studies on individual and family psychopathological factors, as well as
      reports on the effects of psychoeducational/psychotherapeutic interventions on
      glycemic control in patients with IDDM aged <18 years. The analysis of the
      literature indicates that while evidence on the relationship between individual
      factors and metabolic control is still mixed, in part due to methodological
      issues, results from family studies do suggest that patients in dysfunctional
      families and children of parents with high degrees of psychopathology present
      with poor glycemic control. As for the effects of
      psychoeducational/psychotherapeutic interventions, limited but increasing
      evidence shows that they can actually contribute to improve metabolic control. We
      finally suggest some future underexplored avenues of research in the field,
      including studies on the psychopathological and neurobiological mechanisms
      underlying the above mentioned findings. All this body of research should provide
      a strong empirical rationale for allocating resources in order to include
      psychiatrists within the interdisciplinary diabetes health care team.

PMID- 22856233
TI  - The prevalence and pulmonary consequences of anxiety and depressive disorders in
      patients with asthma.
AB  - The aim of this study was to determine the prevalence of anxiety and depression
      symptoms in outpatients with treated asthma and to determine the influence of
      anxiety and depression symptoms on lung function and asthma symptoms. The study
      was conducted in the pulmonary clinic of the Department of Pulmonary Diseases,
      Osijek University Hospital Centre, on 200 outpatients with asthma, aged 18-50
      years, of which there were 65.5% women and 35.5% men. Each patient underwent a
      clinical examination with an extensive anamnesis and lung auscultation. The lung
      function was tested by spirometry. Demographic data and data on general and
      socioeconomic characteristics were evaluated using a questionnaire created
      internally for the purposes of this research, psychological status was assessed
      by HAD questionnaire, and Q test was used as a measure of asthma control. Based
      on the HAD questionnaire, 44.5% of asthma patients met the criteria for anxiety,
      and 24.5% of asthma patients met the criteria for depression. There was no
      significant correlation between asthma symptoms and the degree of anxiety or
      depression, while the pulmonary function of asthma patients negatively correlated
      with the degree of anxiety and depression. Pulmonary function in asthma patients
      with symptoms of anxiety and depression was significantly poorer than in asthma
      patients without anxiety and/or depression symptoms. The results show that among
      asthma patients there are large number of those who have symptoms of anxiety and
      depression. Asthma patients with symptoms of anxiety and depression have poorer
      lung function than patients with only asthma symptoms, however there is no
      significant correlation between the lung function and symptoms of asthma. We have
      confirmed that patients with anxiety symptoms visit general practitioners or EMS
      significantly more when compared to patients with depression symptoms.

PMID- 22856234
TI  - Time trends in prescribing habits of anxiolytics and antidepressants in Slovenian
      family practices (with emphasis on elderly patients).
AB  - The aim of the study was to investigate prescription of anxiolytics and
      antidepressants among Slovenian family physicians regarding drug class with an
      emphasis on the elderly population and possible time-trends. Exploratory survey
      and register-based analysis of anxiolytic and antidepressant prescriptions of one
      hundred family physicians in Slovenia was performed in 2005 and 2008. Drugs
      included in the study were classified according to the Anatomical-Therapeutic
      Chemical (ATC) drug classification system, and ATC data were used to calculate
      defined daily doses (DDD) per 1,000 practice population per day. The most often
      prescribed anxiolytics and antidepressants were identified and
      anxiolytic/antidepressant ratio was estimation by patient age-group for the two
      studied years. Benzodiazepines showed highest share in the overall utilization of
      psychotropic drugs. The ratio between short- and long-acting benzodiazepines
      decreased by about one tenth during the observed period. Long-acting
      benzodiazepines were prescribed more often to the older patients. The decrease in
      anxiolytic/antidepressant ratio from 2005 to 2008 was the smallest in the elderly
      population. Further research is needed to ascertain the prescribers' attitudes in
      order to devise strategies to further improve prescribing performance in elderly
      patients.

PMID- 22856235
TI  - An ethnomedicine study among women in Uremia (North-West Iran).
AB  - During the recent years, ethomedicine has attracted a great deal of attention
      among the investigators throughout the world. Although ethnomedicine seeks, in
      the first place, to compensate for a biological need through providing cures for
      disorders, it, however, is of a cultural nature, too, in that it investigates
      people's behaviors and reactions toward health and the issues related to it.
      Consequently, traditional health must be counted as a component of a society's
      culture. Investigations of people's views toward traditional medicine are capable
      of throwing light on acquaintance with their conducts, customs, traditions and
      behaviors, as well as the social-economic conditions prevailing in their
      environment. In addition, such investigations of public medicine bring about
      familiarities with gradual developments in traditional medical methodologies as
      introduced by culture, economic, or social factors, first into the society, then
      medicine. Familiarizations with cultural diversities in relation to medicine are
      the end results. The present paper comprise an anthropological approach toward
      investigation of ethnomedical practiced by women of Uremia (North-West, Iran).

PMID- 22856236
TI  - Vaginal delivery and continuous epidural analgesia: should we change our clinical
      approach?
AB  - The aim of the study was to investigate the effects of continuous epidural
      analgesia (EA) on the course of vaginal delivery with an emphasis on duration of
      labor and instrumental interventions. In a prospective 2-year trial, the study
      group included singleton vaginal births between 35 and 41 gestational weeks with
      a vertex fetus, in which continuous EA with bupivacaine or chirocaine in
      concentration of 0.125% combined with 2-4 microg of fentanyl or 0.5 microg of
      sufenta was used. The control group was created randomly from laboring patients
      with singleton pregnancies but without EA. The groups were adjusted for
      epidemiological characteristics and compared regarding the obstetric data and
      perinatal outcome. Student t-test and Mann-Whitney U-test were performed for
      normally and non-normally distributed results, respectively. Out of 1284
      patients, 551 pregnant women were included in the study group and 733 in the
      control group. The statistically significant differences between the groups
      related to duration of the first and second stage of labor, frequency of
      premature rupture of membranes, intrapartal complications, and incidence of
      operative deliveries were found. Both stages of labor were significantly
      protracted and the incidence of operative deliveries was higher in the study
      group of patients compared with controls. There is a need for an active obstetric
      approach and management of vaginal deliveries of women who receive continuous EA,
      particularly if it is medically indicated.

PMID- 22856237
TI  - Wegener's granulomatosis: clinico-radiological finding at initial presentation.
AB  - Diagnosis of Wegener's granulomatosis at the early stage is difficult because of
      the nonspecific symptoms which mimic other disorders. The aim of this paper is to
      describe clinical and radiological features of Wegener's granulomatosis (WG) in a
      Serbian population at initial presentation. A retrospective review of 37
      patient's case records was carried out. All those patients were diagnosed with WG
      and they attended the Institute for lung diseases in Belgrade over the period of
      15 years. There were 20 males and 17 females, ranging in age from 18 to 73 years
      (mean age 46.2 years). The mean period from the onset of the first symptoms to
      diagnosis of WG was 4.59 +/- 6.15 months. The criteria of American College of
      Rheumatology were fulfilled in all patients. Twenty-five of 37 patients had
      systemic, generalized form of WG and while 12 of them had a limited involvement
      of upper and lower respiratory system. The frequency of different system
      involvement was: upper respiratory tract 64.8%, lower respiratory tract 100%,
      kidneys 67.5%, musculoskeletal system 40.5%, skin 27.2%, eyes 8.1%, and nervous
      system two patients. ANCA (antineutrophil cytoplasmic antibodies) test was
      positive in 32 ((86.5%) patients, and negative in 5 (13.5%). All patients were
      ANA negative. Histological evidence of granulomatous vasculitis was obtained in
      34 (91.9%), whereas in three patients the diagnosis was based on clinical
      manifestations and positive c-ANCA test. There are minor variations in our data
      when compared with those reported in literature.

PMID- 22856238
TI  - Electrophysiological correlates activated during the Wisconsin Card Sorting Test
      (WCST).
AB  - In the present study we investigated changes in Event-Related Potentials (ERPs)
      during the Wisconsin Card Sorting Test (WCST) in order to identify cognitive
      processes underlying the set-shifting aspects of the task and to determine test
      sensitivity for frontal and prefrontal cortical areas. ERP's were recorded from a
      sample of 20 healthy adults while they performed a computerized version of the
      Grant & Berg (1948) version of the WCST, using 32-channel electroencephalogram
      recordings. The ERP waveforms were calculated for the set-shifting trials, or
      more precisely for the 2nd and the 3rd trials in the WCST series (set change
      condition) and compared to those associated with the last two trials in a series
      before the set change (set unchanged condition). The results indicated changes in
      central frontal and parietal electrodes during attentional set-shifting. More
      precisely, the P300 effect was replicated in this dataset, confirming the claim
      that the WCST measures function of prefrontal cortical areas of the brain.
      However, the obtained wave resembled P3b indicating the working memory component
      of the task. The results suggest that the frontal and parietal cortical activity
      is especially involved in set-shifting during WCST performance. Therefore, these
      electrophysiological results are not consistent with some recent studies that
      question the specificity of WCST as a measure of frontal and parietal lesions.

PMID- 22856239
TI  - Vertebral pathologies and related activity patterns in two mediaeval populations
      from Spain.
AB  - The main aim of this study was to explore the usefulness of several types of
      vertebral pathology as activity markers in osteological populations. A total of
      2165 vertebrae from 124 individuals were studied. They were derived from
      cemeteries in two villages: Villanueva de Soportilla (Burgos, north of Spain),
      with a Christian population, and La Torrecilla (Granada, south of Spain),
      inhabited by Muslims. Degenerative joint diseases, Schmorl's nodes, compression
      fractures and spondylolysis with spondylolisthesis were analysed in individuals
      and separate vertebral pieces. All pathological conditions, except compression
      fractures, were significantly more frequent in males than in females, reflecting
      more intensive labour conditions for males. They were significantly more frequent
      in males from Villanueva, a border population of peasant-soldiers, than in males
      from La Torrecilla. They were also significantly more frequent in females from
      Christian Villanueva than in those from Muslim La Torrecilla, where the women
      mainly worked at home. The benefits and limitations of the study of these
      vertebral pathologies are discussed.

PMID- 22856240
TI  - Influence of the position on the bicycle on the frontal area in road cyclists.
AB  - The aims of the present study were to determine whether the estimations of the
      frontal area of the combined cyclist-bicycle (APCB) obtained with the Heil's non
      logarithmic prediction equations (NPE) in the stem position (SP), brake hoods
      position (BHP) and drops position (DP) are comparable to the measured APCB with
      the computerized planimetry (CP) method, and to analyse with the CP method and
      the NPE the influence of the body position on the APCB. Nineteen participants
      competing in the Spanish Road Cycling First division took part in the study. The
      NPE overestimated the APCB in the BHP and in the DP compared with the measured
      APCB with the CP method (6.9% and 5.1%, respectively; p<0.05). Significant
      differences among the three positions were obtained with the CP method. The
      overestimation of the APCB with the NPE in the BHP and in the DP and the less
      sensitivity of the NPE to show significant differences between the SP and DP
      suggest that the NPE are not appropriate to accurately predict the APCB.

PMID- 22856241
TI  - Mucormycosis of the nasal ala in a leukemic (M7 AML) child. Is surgery of the
      nasal defect indicated?
AB  - Anterior tamponade with Surgicel (oxidized cellulose) was performed on a 5-year
      old girl with megakaryoblastic leukemia (M7 AML) and epistaxis. Several days
      later necrosis of the nasal ala occurred. Debridement was performed and
      mucormycosis caused by Rhizopus was found in the material. Having cured
      mucormycosis, a defect of the complete nasal ala remained. The question of a
      surgical resolution of the disfiguring nasal defect arises.

PMID- 22856242
TI  - Risk factors for acute respiratory tract infections in children.
AB  - Acute respiratory tract infections (ARTI) are the most common cause of childhood
      morbidity and an important public health problem. The aim of this study was to
      identify the significant risk factors for ARTI in children. The study took place
      in Ivankovo which is a rural area of Eastern Slavonia and with small socio
      economic differences. The study population were 159 children who were 3-5 years
      old at the time of the study, and who were registrated at doctor's office
      Ivankovo. The study was conducted retrospectively through a questionnaire from
      January 2008 to December 2008. The risk factors studied were the gender,
      breastfeeding history, any atopic manifestation in the form of atopic eczema,
      rhinoconjuctivitis and/or asthma, the size of the family, parents smoking habits
      and main form of childcare. The number of ARTI requiring the consultation of a
      doctor throughout 2007 were measured; and whether ARTI had been treated with
      antibiotic or there were recommendation for symptomatic treatment only. Results
      of this research show that the risk factor for consulting a doctor because ofARTI
      in children was passive exposure to cigarette-smoke. For receiving antibiotics
      because of ARTI in children, the risk factors were passive exposure to cigarette
      smoke and atopic manifestation. By giving the available evidence, parents must be
      told that ceasing smoking offers a significant opportunity to reduce the risk of
      ARTI in their children.

PMID- 22856243
TI  - Croatian children's views towards importance of health care information.
AB  - The aim of research was to investigate: the need for health care information of
      Croatian adolescents aged from 13 to 18 years; the difference in evaluation of
      the frequency of receiving information between hospitalized and healthy children;
      if the hospitalized children expectations about the frequency of receiving health
      care information differed significantly from information they have actually
      received; whose information was most comprehensible to the hospitalized children
      (doctors, parents, other health care givers). The children were either
      hospitalized in the pediatrics departments or were high schools pupils (healthy
      children). The hospitalized children "Completely agreed" (92.7%) with the
      statement "When I am sick, I should receive information about my health" in
      comparison to the healthy children (85.1%). In comparison to healthy children,
      the hospitalized children assessed that doctors, other health care givers and
      parents should give them information more frequently. The experience of
      hospitalized children indicate that they received less information then they have
      actually excepted. The information received from doctors was mostly in
      correlation with the understanding of this information. We concluded that the
      children want to be informed about their health, especially hospitalized
      children. Health care professionals should offer understandable health care
      information according to the children's expectation.

PMID- 22856244
TI  - Secular changes in growth and obesity in perinatal population.
AB  - The survey was conducted during the last 25 years and included 2414 healthy women
      who delivered in "Sestre milosrdnice" University Hospital Center in Zagreb,
      Croatia and their newborns. The aim was to establish the secular trend of some
      anthropological factors through two generations. Anthropological features such as
      pre-pregnancy weight, body mass index before pregnancy, height, age, place of
      residence, educational level, parity and the newborn weight were registered. The
      study was randomized. The mothers from the city of Zagreb and the surrounding
      villages, rural areas are examined. The women age was different and also
      different levels of education and socioeconomic status. The study included women
      who had not given birth yet, who had delivered once, twice, and three or more
      times. Maternal height in 25 years increased by 3.1cm. and increases with
      education. The pre-pregnancy weight increased 2.8 kg and increases with age,
      parity and rural life. The body mass index (BMI) which the women had before
      pregnancy was calculated, and according to its value the participants were
      divided in three groups: with normal weight, overweight and fat. Among the
      studied periods BMI does not differ significantly, but does differ significantly
      with respect to the ordinal number of births, parity, age and living environment.
      Higher BMI was associated with deliveries to heavier children.

PMID- 22856245
TI  - Biomotor status and kinesiological education of students aged 13 to 15 years -
      example: karate.
AB  - The aim of this paper was to obtain information relevant for efficient selection
      in karate, based on comparison of biomotor status of male/female 7th and 8th
      grade students in primary school "Bijaci" from Kastel Novi and karate
      practitioners and non-practitioners (cadets) in Croatia. For this purpose, a
      sample was drawn of 352 primary school students (150 males and 152 females) and
      50 karate practitioners (25 males and 25 females), all aged 13 to 15 years, and 2
      morphological measures (body height and body mass) and a battery of 6 motor tests
      was used. A biomotor system which determines the situation efficacy in male and
      female karate practitioners was defined based on the comparison of test results
      of students from Kastela, Croatian karateka and Croatian standards, factor
      analysis of applied variables and discriminant analysis of those variables
      between karate athletes and students from Kastela. In male karate athletes,
      general motor efficacy in karate is based on explosive strength of jumping type,
      repetitive strength of the trunk and coordination, followed by flexibility,
      static strength of the arms, and movement frequency speed. In female karate
      athletes, integration of force, coordination, muscle tone regulation and speed is
      dominant for achieving success in karate. Female karate athletes use speed and
      fine muscle tone regulation in motor functioning more than male karate athletes,
      who use basic strength more.

PMID- 22856246
TI  - Gender differentiations of cognitive-motor functioning in prepubertal and
      pubertal children.
AB  - The aim of this study was to determine cognitive and motor status factors in
      female and male children aged 10-14, as well as developmental and/or integration
      functions according to gender. The study included 162 girls and 134 boys aged 10
      14, divided into four groups: 84 girls aged 10-12 (mean age 11.26, SD 0.68), 84
      boys aged 10-12 (mean age 11.41, SD 0.50), 78 girls aged 13-14 (mean age 13.52,
      SD 0.63) and 50 boys aged 13-14 (mean age 13.21, SD 0.53). The significance of
      quantitative differences between boys and girls in the overall system of
      variables was defined based on the results of canonic discriminant analysis of
      variance, and within each variable based on the results on univariate analysis of
      variance (ANOVA). In the younger age group (10-12 years), girls were superior to
      boys in a test assessing flexibility (Seated straddle stretch), whereas, compared
      to girls, boys had greater strength of the trunk (Crossed-arm sit-ups), greater
      explosive strength ofjump and sprint type (Standing broad jump and 20 m dash),
      and coordination (Obstacle course backwards and Steps laterally). In the older
      age group (13-14 years) differences in flexibility were even more prominent in
      favor of girls, whereas the differences in explosive strength increased in favor
      of boys, especially of the throwing type with better agility (Steps laterally),
      balance (Board balance) and greater static strength of arms and shoulders (Bent
      arm hang). In order to determine qualitative differences between pubertal and
      prepubertal girls and boys, the matrix of variable inter-correlations was
      factorized by the procedure of principal components procedure, that were then
      transformed to promax solution. The results showed that cognitive functioning had
      a significant role in the motor efficacy of girls and boys aged 10 to 14. In the
      age group of 10-12 years, in females, cognitive functioning is related to the
      motor system which integrates the regulation of muscle tone with
      agility/coordination, whereas in males there is a relation between cognitive
      abilities and the regulator of speed of upper extremities movement frequency. In
      the age group of 13-14 years, in females, cognitive functioning is involved in
      forming the factors for regulation of coordination and the intensity of energy
      mobilization in lower extremities, and to some degree, in the factor for
      regulation of intensity of energy mobilization in upper extremities and strength
      of the trunk, whereas in males the integration of synergetic regulation of
      movement in terms of balance and agility in terms of speed of direction change is
      carried out with significant involvement of cognitive abilities.

PMID- 22856247
TI  - Effect of micronutrient fortified biscuit supplementation on the weight, height
      and BMI of adolescent girls.
AB  - A study was designed to determine the effect of supplementation of biscuits with
      and without micronutrients on the weight and height of adolescent girls (N=107)
      in the age group of 10 to 16 years studying in a government school in Jaipur
      city. Data on weights and heights were collected using standardized techniques.
      Hundred grams of biscuits furnishing 497 kcal and 11.36 g of protein per day for
      all working days in a 4 month period was provided to the control group (N=54);
      and 100 g of biscuits fortified with one RDA levels of vitamin A, iron, folic
      acid, vitamin C and iodine was provided to the experimental group (N=53).
      Supplementation with biscuits resulted in significant weight gains of 1.85 kg and
      2.00 kg in the control and experimental groups, respectively. As per weight for
      age, the increments in the normal category was from 27.8% to 40.7% in adolescent
      girls of the control group and from 34.0% to 45.3% in those of the experimental
      group. There was statistically significant improvement in the mean BMI, as well
      as in various grades of chronic energy deficiency, after intervention. In
      conclusion, intervention with biscuits with and without nutrients resulted in
      significant improvements in weight gain and BMI.

PMID- 22856248
TI  - Nutritional assessment by mid-upper arm circumference of santal adults of
      Purulia, West Bengal, India.
AB  - The present community based cross-sectional study was undertaken to determine the
      prevalence of undernutrition using mid-upper arm circumference (MUAC) among adult
      (> 18 years) Santals of Purulia District, West Bengal, India. It was undertaken
      at 10 villages of the district. A total of 520 (217 males and 303 females)
      subjects were measured. Commonly used indicator i.e., MUAC and BMI, were used to
      evaluate the nutritional status of the subjects. More women (64.7%) then men
      (54.4%) based on MUAC and women (59.4%) then men (34.6%) based on BMI were
      undernourished. Significant sex difference both in MUAC (t=2.378, p<0.05) and BMI
      (t=4.971, p<0.001) were observed. Significant age group difference for MUAC was
      observed (F=8.93***, df=3) for men and (F=9.52***, df=3) for women. For BMI,
      these values were F=10.10*** (df=3) F=6.17*** (df=3) respectively. In conclusion,
      we found that adult Santals of both sexes were under critical nutritional stress,
      women and the oldest among them were the most.

PMID- 22856249
TI  - Tracking variability: recent anthropometric data for croatian population and
      comparison with other world populations.
AB  - The variability that exists within the populations of individual countries and
      the variability that exists between the populations of different countries are
      both of interest in practical application. For these reasons, a comparison is
      made in this work between certain anthropometric variables of our sample of
      Croatian population and anthropometric variables that are available for other
      human populations in the world of the same or a similar age. The total sample was
      1,372 subjects aged from 23 to 59 years old. For the purpose of comparison, data
      were taken from the study "International Data on Anthropometry" which provides an
      overview of anthropometric variables for many world populations, as well as data
      from Rudan's research that was carried out on Croatian population in the late
      seventies of the last century. Mean value, standard deviation and coefficient of
      variation have been calculated for every measured parameter. A comparison between
      the two research samples of Croatian population fairly displays up going trend,
      for body mass and other bodily dimensions, formed in three decades of difference.
      Mean value for body height in Rudan's sample is 161.0 cm, and for Bubas's sample
      in this research was 170.6 cm, both values state for Croatian population but with
      difference of more than 30 years. Human biologists use term "secular trend" to
      describe alterations in the measurable characteristics of a population of humans
      that occur over a century. Accordingly, in adult age, the rate of gain,
      concerning body height, is 10 to 30 mm per decade. The changes in body
      proportions during recent decades are less marked than those in body size, but
      the relationships between stature and weight within one national group have
      changed significantly.

PMID- 22856250
TI  - The latent structure of soccer in the phases of attack and defense.
AB  - With the aim of establishing the latent structure of tactical elements in the
      attack and defense phases of soccer 117 tactical elements of soccer were defined
      and their importance assessed by means of 30 variables that determine the basic
      segments of the game of soccer. 93 attack and 24 defense tactical elements were
      chosen as the entity sample and described by the 15 variables of the attack phase
      and 15 variables of the defense phase. Ten competent soccer experts determined
      the characteristics of the aforementioned entities by means of 30 variables. The
      experts graded from 0 to 5 the impact of every entity (tactical technique) on the
      individual variables that describe soccer in its phases of either attack and
      defense. A high level of inter-expert agreement was reached in regard to the
      properties of attack and defense techniques, as demonstrated by the objectivity
      coefficients. According to principal component factor analysis and the Kaiser and
      Guttman rule a total of five significant latent dimensions were obtained:
      finishing efficiency, ball possession performance, counter-attack efficiency,
      combined defense performance, and obstruction and redirection of the opposing
      team's attack build-up. The research partly resolved the issue of the
      hypothetical structure of tactical techniques in soccer by dividing the game into
      phases and sub-phases, attack and defense players'positions, and types (styles)
      of play in the attack and defense. If it is clear which movement structures have
      the most significant influence on the efficiency on a particular playing position
      and performance in the sub-phases and styles of play, it would be possible to
      create such training operators that will facilitate the formation of the most
      important motor skills in soccer.

PMID- 22856251
TI  - Comparative assessment of the acute ankle injury by ultrasound and magnetic
      resonance.
AB  - We compared ultrasound (US) with magnetic resonance (MR) findings of muscle
      tendon and ligaments (mt&l) of 17 men and 13 women, 16-66 years old, who suffered
      from acute ankle injury without bone fracture visible on conventional
      radiographs. Joint effusion (JE), and injury of the Tibials anterior muscle
      tendon (TAmt), Calcaneofibular ligament (CFl), Long flexor of the great toe
      muscle tendon (LFGTmt), Short peroneus muscle tendon (SPmt), Long peroneus muscle
      tendon (LPmt), and Anterior talofibular ligament (ATFl) were assessed by the US,
      at seven days, and MR, at seventeenth day. Grading of ligament and muscle tendon
      injury as stretching (Grade 1), partially ruptured (Grade 2), and complete
      rupture (Grade 3); no lesion was considered to be Grade 0. Joint effusion and
      ATFl were the most common lesions whereas the TAmt lesion was the least frequent:
      JE approximately ATFl > SPmt approximately LPmt > LFGTmt approximately CFl
      approximately TAmt. Both US and MR were equally sensitive in detecting the
      presence (or absence) of the mt&l ankle injury, whereas US was less specific than
      MR in detecting G3 injury.

PMID- 22856252
TI  - Total knee replacement surgery is followed by transitory endothelial dysfunction.
AB  - Acute coronary syndrome (ACS) presents today the leading group of post-operative
      cardiovascular complications, while endothelial dysfunction (ED) is one of the
      key elements in its development. The chronic ED represents thus the basis for the
      gradual development of atherosclerotic changes, while its sudden aggravation
      leads to ACS. The persistent ED occurs due to the effects of chronic
      cardiovascular risk factors, while according to the available studies it can also
      develop or aggravate under the impact of different acute events. We have directed
      this study to the investigation of the dynamic of endothelial function before and
      after a major orthopaedic surgical intervention. This randomised prospective
      study included 19 patients that underwent the intervention of total knee
      replacement and 20 healthy examinees of the adequate age and gender High
      resolution ultrasound test based on the flow mediated dilatation of the brachial
      artery is what at we carried out at the beginning of the research, respectively
      12, 24, 48 and 72 hours, as well as 7 days after the surgical intervention. The
      starting values of the FMD test were within the normal range in both groups,
      although the ability of dilatation upon stimulus was significantly lower in the
      investigated group. The FMD percentage change in the total sample was negatively
      connected with the body weight, not having shown additional connections with
      other cardiovascular risk factors. During the early post-operative period, a
      significant transitory lowering of the FMD percentage change was recorded, having
      reached the lowest value 24 hours after the surgery. During the seven-day
      prospective surveillance, no significant cardiovascular complications were
      recorded. Further research is necessary in order to confirm these results as well
      as the testing of the possible connection of the described post-operative
      transitory endothelial dysfunction with the development of cardiovascular
      complications and the adverse event.

PMID- 22856253
TI  - Treatment of infected tibial nonunion with bone defect using central bone
      grafting technique.
AB  - Treatment of infected tibial nonunion with bone defect represents a challenge for
      every orthopaedic surgeon. Various methods of treatment have been described for
      nonunions with infection, bone loss or both. One of them is the central bone
      grafting technique, which is a safe and effective treatment for nonunions of the
      tibia. The technique involves placement of autogenous cancellous bone from the
      iliac crest on the anterior surface of the interosseous membrane with the aim of
      creating a tibiofibular synostosis. We present the results of uncontrolled,
      retrospective and continuous series of ten patients treated by a central bone
      grafting technique for infected tibial nonunion with bone loss. Mean follow-up
      period was 12 (10-15) years. Most injuries were a result of war injuries.
      Clinically and radiologically confirmed bony healing with total consolidation of
      the graft was achieved in all patients within a period of 10-12 months without
      further bone grafting. The newly-formed bone mass was able to fulfil the
      mechanical and functional demands of everyday life activities. Once again, the
      central bone grafting technique has shown to be a safe, reliable and effective
      method of treatment for infected tibial nonunion with bone defect.

PMID- 22856254
TI  - The impact of wool in the patients with chronic non-specific low back pain.
AB  - The aim was to assess the effect of wool underwear use in patients with chronic
      non specific low back pain. The study employed two-group, experimental design. A
      total of 48 patients with chronic non specific low back pain were selected for
      the study. They were distributed into two groups: a control group and a treatment
      group. The 24 patients in each group were randomly selected and the compositions
      of the two groups. The patients in the treatment group wore woolen underwear
      during the experimental period of 2 month. All patients were assessed at the
      beginning the trial (pre-test) and the end of 8th (post-test) week. Data were
      collected using the visual analogue pain scale, Oswestry Disability Index and
      Schober test measurements. Patients in the treatment group reported significant
      improvements in their conditions including a reduction in pain levels and
      Oswestry Disability Index, and Schober test measurements increased (p<0.001).
      Patients with chronic non-specific low back pain who wore wool underwear
      experienced significant improvements in pain intensity, disability, and lower
      back flexibility.

PMID- 22856256
TI  - Immediate fatal outcome vs. fatal outcome within the first 48 hours following a
      severe traffic trauma--analysis of the possible effect of alcohol intoxication on
      the outcome.
AB  - This paper is a retrospective analysis of data on 278 persons with fatal outcomes
      in traffic accidents in Osjecko--baranjska County, Croatia, during a five-year
      period. The observed sample of casualties was divided according to the time of
      fatal outcome into three groups: immediately deceased (139 or 50.0%), deceased
      within the first 48 hours (84 or 30.2%) and deceased after 48 hours (55 or
      19.8%). A comparison of data was made for the first two groups of casualties,
      based on the level of alcohol intoxication, and an analysis of the possible
      influence of alcohol intoxication on an early outcome of severe trauma, which was
      defined as immediate fatal outcome and fatal outcome within the first 48 hours
      following the trauma. Casualties from the group of immediately deceased had a
      significantly higher average blood alcohol level than casualties from the group
      of persons deceased within the first 48 hours (shown through arithmetic mean of
      0.81 g/kg vs. 0.33 g/kg, p =0.000). A binary logistic regression analysis showed
      that every increase in blood alcohol level by 1 g/kg also increased the odds of
      an immediate fatal outcome by 1.92 times (p=0.004). CONCLUSION: Beside increased
      risks of traffic accidents, the collected data showed that alcohol intoxication
      of accident participants also increases their chances of an immediate fatal
      outcome.

PMID- 22856255
TI  - Causal connection of non-specific low back pain and disc degeneration in children
      with transitional vertebra and/or Spina bifida occulta: role of magnetic
      resonance--prospective study.
AB  - The problem of low back pain (LBP) in children is very common and many
      specialists are dealing with it in everyday practice. The cause for low back pain
      often is not found and classified under the diagnosis of non specific low back
      pain. The objective of this prospective study is to determine wether children
      with non specific low back pain and existence of anomalies in LS spine
      (transitional vertebra- TV and/or Spina bifida occulta SBO) also have the
      degeneration of the intervertebral disc (DD) L4-L5 and/or L5-S1. This prospective
      study included 69 patients from 8 to 16 years of age (X 12.81) of whom 40 were
      male (57.97%), and 29 female (42.03%). They all were examinated in University of
      Zagreb, "Sestre milosrdnice" University Hospital Center, Zagreb Children's
      Hospital, Department of Orthopaedic, Zagreb, Croatia. The reason of their visit
      was non specific low back pain. Pain was measured by visual analog scale (VAS)
      and mean score was three, duration of pain was between two and four weeks. Also,
      pain was sporadic, during daytime and not connected with level of physical
      activity. They all have undergone an algorithm of radiological examinations.
      Standard AP and LL radiographs (RTG) were made, as well as magnetic resonance
      (MR) of LS spine and sacrum in sagittal and transversal plane in T1 and T2
      weighted sequence. The anomalies of L5 and S1 were found in 65 patients:
      transitional vertebra classified according to Castellvi et al. and SBO. In MRI in
      T2 weighted sequence DD was found in 61 patients which was classified modified
      from Pearce. Data analysis and comparison showed that 56patients with TV and/or
      SBO have changes on vertebral dynamic segment L5-S1 (VDS) and that means DD. In
      13 patients only DD or spinal anomaly (TV and/or SBO) were found. Correlation
      between anomalies and DD in those patients was established by McNemar analysis
      and has shown significant difference (p=0.581) in favour of the patients with
      anomaly and DD. This has established that all of 56 patients with spinal anomaly
      could have DD as known cause of LBP.

PMID- 22856257
TI  - Unexpected sudden death due to recreational swimming and diving in men in Croatia
      in a 14-year period.
AB  - The article deals with 17 sudden deaths which occurred during recreational
      swimming and diving in men in Croatia in a 14-year period: from January 1, 1998
      to December 31, 2011. The sample is taken out from the total number of 61 sudden
      deaths in men during or immediately after sport or recreational exercise.
      Included are also sudden deaths of 8 foreigners spending holidays at the Croatian
      Adriatic Coast. In all of them forensic medicine autopsy was done. Thirteen males
      from Croatia died during recreational swimming. Three of them were aged 15-29
      yrs: one had signs of hypertrophic cardiomyopathy, the second suffered from
      chronic myopericarditis with left ventricular aneurysm, and the third had
      cardiomegaly and blood alcohol level of 1.7 per thousand. Five were aged 30-64
      yrs: four of them have suffered from coronary atherosclerosis and left
      ventricular hypertrophy of 15-18-18-22 mm, and one with left ventricular
      hypertrophy drowned suddenly, probably because of malignant ventricular
      arrhythmia. The fifth suffered stroke and drowned. Five elderly men, aged 65-85
      yrs, have suffered from coronary atherosclerosis, myocardial fibrosis or
      myocardial scars, and three of them had left ventricular hypertrophy of 19 mm.
      Four males died during recreational diving. One aged 26yrs drowned, at autopsy he
      had left ventricular hypertrophy of 17 mm. Three males were middle-aged: two had
      coronary atherosclerosis, two of them had a severe degree of coronary
      atherosclerosis and one had coronary atherosclerosis of medium degree but with
      myocardial fibrosis and left ventricular hypertrophy of 18 mm. Seven male
      foreigners died, five of them during swimming: two aged 30-64 and two aged 65-85.
      They all have had coronary atherosclerosis: one of them had an acute myocardial
      infarction of the posterior wall, and one hypertrophic cardiomyopathy as well.
      One middle-aged and one elderly man died during diving, and both had an acute
      myocardial infarction of the posterior wall. One elderly foreign woman died
      during swimming, she had coronary atherosclerosis and a myocardial scar. In
      Croatia, death rate during both swimming and diving in men aged 15-29 years
      amounted to 0.63/1,000.000 (p=1.0000); in those aged 30-64 it reached
      0.56/1,000.000 (p=0.3698), and in those aged 65-85 it was 1.41/1,000.000
      (p=0.1849). The death rate during swimming in men aged 15-29 amounted to
      1.47/1,000.000 (p=0.9864), in men aged 30-64 it reached 0.35/1,000.000
      (p=0.2245), and in those aged 65-85 it was 1.41/1,000.000 (the difference is
      significant, p=0.0472). The death rate during diving in men aged 15-29 was
      0.16/1,000.000, and in men aged 30-64 the observed rate was 0.21/1,000.000
      (p=1.0000).

PMID- 22856258
TI  - Residues of lindane in adipose tissue of lambs and sheep from islands Krk and
      Cres.
AB  - Concentrations of lindane from adipose tissue i.e. omentum of sheep from
      homesteads of island Krk that were treated with lindane, were compared with the
      concentrations of lindane measured in adipose tissue of non treated sheep from
      husbandry cooperative on island Cres. Evaluation of food safety for this samples
      were estimated by comparing obtained results and maximum tolerance concentration
      (MTC) for lindane (2.0 and 0.2 mg/kg). In treated lambs from Krk measured
      concentrations of lindane were in range from 0.0038 to 1.8644 mg/kg, and in
      treated sheep from 0.0094 to 1.646 mg/kg. In control group of lambs and sheep
      concentration of lindane was < or = 0.0051 mg/kg. Estimation of food safety based
      on the results from this research are discussable, regarding the fact that MTC
      prescribed before year 2007 was 2.0 mg/kg. When the new law Regulations of MTC
      for residues of pesticides in food and animal feed (NN 119/07) came into the
      force prescribed MTC was 0.02 mg/kg. If food safety of sheep meat from Krk would
      be estimated based on latter, then 73.4% of samples of lamb meat and 80% of sheep
      meat could be proclaimed unsafe for human consumption. It is encouraging that
      after completion of using lindane in year 2005, levels of lindane in adipose
      tissue of lamb from Krk in year 2006 were under the concentration set by new
      legislate (< 0.02 mg/kg).

PMID- 22856259
TI  - Alterations in the masseter muscle and plasma IL-6 level following experimentally
      induced occlusal interference and chronic stress--a study in rats.
AB  - This study was undertaken to examine the alteration of masseter and plasma
      interleukin-6 after inducing occlusal interference and chronic stress. Male
      Wistar rats were submitted to chronic stress procedure, exposed to occlusal
      interference, or exposed to both mentioned procedures. Whole blood and masseter
      tissue were collected to determine interleukin-6 level, measured by means of
      ELISA. Masseter pain was evaluated using the orofacial formalin test. Masseter
      interleukin-6 level was significantly higher in animals submitted to combination
      of occlusal interference and chronic stress than in the control group (p<0.05).
      There was positive and significant correlation between pain response and masseter
      interleukin-6 level (r=0.5741; p<0.0003). No significant differences in plasma
      interleukin-6 level were found between groups (p>0.05), as well as no correlation
      with pain (p>0.05). Combination of occlusal interference and chronic stress leads
      to strong local reaction characterized by high levels of masseter interleukine-6.
      High concentrations of muscle interleukin-6 and its correlation with pain point
      to inflammatory background of masticatory muscle pain.

PMID- 22856260
TI  - Current trends in breast reduction.
AB  - Results of our study describe the long term effects of reduction mammaplasty.
      Many women with excessively small or large breasts have an altered personal self
      image and often suffer from low self-esteem and other psychological stresses.
      This procedure is designed to reduce and reshape large breasts, and since the
      size, shape, and symmetry of a woman's breasts can have a profound effect on her
      mental and physical well-being it is important to observe the patient's long-term
      outcome. Currently, breast reduction surgery is safe, effective and beneficial to
      the patient. In Croatia, reduction mammoplasty is often excluded from the general
      health care plan. The distinction between "reconstructive" versus "cosmetic"
      breast surgery is very well defined by the American Society of Plastic Surgeons
      Board of Directors. Unfortunately, the Croatian Health Society has yet to
      standardize such a distinction. There is an imperative need for evidence-based
      selection criteria. We retrospectively analyzed data of 59 female patients
      suffering from symptomatic macromastia who underwent reduction mammaplasty over a
      16 year period (1995 until 2011). Our aim was to compare and contrast the various
      techniques available for reduction mammaplasty and to determine, based on patient
      outcome and satisfaction, which technique is most suited for each patient. The
      results of our study generally reinforce the observation that reduction
      mammaplasty significantly provides improvements in health status, long-term
      quality of life, postsurgical breast appearance and significantly decrease
      physical symptoms of pain. A number of 59 consecutive cases were initially
      treated with the four different breast reduction techniques: inverted-T scat or
      Wisa pattern breast reduction, vertical reduction mammaplasty, simplified
      vertical reduction mammaplasty, inferior pedicle and free nipple graft
      techniques. The average clinical follow-up period was 6-months, and included 48
      patients. The statistical analysis of the postoperative patient complications
      revealed a significant positive relationship in regards to smoking. The majority
      of these complications were wound related, with no significant relationship
      between patient complications and variables such as age, BMI, ASA score,
      resection weight of breast parenchyma, nipple elevation, duration of surgery, and
      type of pedicle. The higher number of complication correlated with a lower volume
      of parenchyma resection (rho=-0.321). Overall satisfaction with the new breast
      size (79%), appearance of the postoperative scars (87%), overall cosmetic outcome
      score (91%), overall outcome (100%), psychosocial outcome (46%), sexual outcome
      (85%), physical outcome (88%), satisfaction with preoperative information data
      (92%), and finally satisfaction with overall care process (96%) was calculated.
      As expected, the physical symptoms disappeared or were minimized in 88% of
      patients. Each method of breast reduction has its advantages and disadvantages.
      The surgeon should evaluate each patient's desires on the basis of her physical
      presentation. Breast reduction surgery increases the overall personal and social
      health; not only for the patient, but for their family and friends as well. It is
      an imperative that every surgeon is aware of this, in order to provide the
      highest level of care and quality to their patients.

PMID- 22856261
TI  - The carcinoid tumour in Meckel's diverticulum: how to treat young adults with
      appendicitis?--Case report.
AB  - This case reports the concomitant and unexpected finding of carcinoid tumour
      within a Meckel's diverticulum presenting as an acute abdomen due to gangrenous
      appendicitis in a young adult male. Both Meckel's diverticula and carcinoid
      tumour are rare clinical entities, and carcinoid tumours occurring within a
      Meckel's diverticulum are even more uncommon. The initial clinical presentation
      of carcinoid tumours occurring in a Meckel's diverticulum is usually similar to
      that of appendicle carcinoids.Carcinoid tumours are the most common primary
      tumour of the small bowel. They resemble appendicle carcinoids to the extent that
      they are usually small, single, and asymptomatic. Surgical treatment of Meckel's
      diverticula is recommended procedure. By presenting this case we wished to stress
      the value of systematic identification and removal of the diverticulum during
      laparotomy and to underline the importance of exploration the Meckel's
      diverticulum particularly in case of young adult subjects.

PMID- 22856262
TI  - Primary Ewing's sarcoma of the kidney: a case report.
AB  - Primary adult Ewing's sarcoma is a rare entity. They most commonly occur in
      children and young adults. 6% of them are localized extraosseously. We present a
      case of a 51 year old patient with primary renal Ewing's sarcoma and multiple
      metastases in liver and iliac bone. Patients with metastatic disease are usually
      treated with aggressive chemotherapy and have a poor outcome. Our patient
      underwent complete surgical excision of tumour, and was treated with aggressive
      chemotherapy, respectively. Two and half years after presentation he is well,
      without any symptoms.

PMID- 22856263
TI  - Preventative valve-sparing aortic root replacement and pregnancy outcome in
      Marfan syndrome.
AB  - In Marfan syndrome, with dilatation of the aortic root secondary to an underlying
      connective tissue defect, pregnancy can cause hemodynamic stress leading to the
      development of an aortic aneurysm and even a fatal aortic dissection. In the
      presence of existing aortic root enlargement and a family history of aortic
      dissection, preventative elective surgery is suggested. Aortic root replacement
      with or without a valve-sparing procedure is superior to total aortic root
      replacement with prosthetic valve/tube graft. It provides excellent survival with
      low rates of aortic - valve related complications.

PMID- 22856264
TI  - Disposal of the body after murder committed by juvenile offender.
AB  - Disposal of the body by setting in concrete or sealing with bricks represents
      relatively rare form of corpse hiding after crime. We report a unique case of
      juvenile offender who killed his father and subsequently concealed the body. The
      victim had been reported missing by members of his family but the body was not
      found until 12 months later. Hidden in concrete body was well preserved allowing
      not only identification of the victim but also determination of the cause of
      death.

PMID- 22856265
TI  - Antituberculosis consortium founded in Rijeka (Croatia): implementation of public
      health measures between 1924-1945.
AB  - Between two World Wars the city of Rijeka was a port and industrial town whose
      infrastructure failed to provide adequate living conditions for numerous workers
      and their families. Insufficient organization of the health care system, poor
      living conditions-especially among the poor, low hygienic standards combined with
      a large number of transitory citizens made city and its citizens vulnerable to
      tuberculosis. Between 1924-1945 Rijeka was a part of the Kingdom of Italy.
      Therefore, the fight against tuberculosis was organised according to Italian
      public health plan and laws. In 1925, Antituberculosis consortium was founded in
      order to organise and coordinate antituberculosis activities in the city region.
      Despite its ambitious administrative measures it was unsuccessful in the field:
      Rijeka had a high mortality and morbidity rate due to tuberculosis. This article
      is based on unpublished archival material.

PMID- 22856266
TI  - Instruments for measuring service quality in sport and physical activity
      services.
AB  - Studies that conceptualize and measure quality in sport services date back to the
      last two decades. The present study aims to examine quality in sport services in
      terms of the classification of participant services and spectator services and to
      provide a summary of the empirical studies carried out to date. This study
      demonstrates that sport services literature is still in its infancy and no
      agreement exists on the developed models. Furthermore, the research models
      examined indicate that sports services not only possess different attributes and
      dimensions than other service industries but also differ in themselves.
      Consequently, the produced models need to be tested in the future on different
      sample groups for further clarification.

PMID- 22856267
TI  - The influence of environment and energy macro surroundings on the development of
      tourism in the 21st century.
AB  - Trying to anticipate the future of tourism may be a particularly fraught task.
      However, this does not mean that trying to predict the future of tourism is not
      without value. From a business perspective, examining the future enables firms to
      anticipate new business conditions and develop new strategies. From a destination
      perspective, reflections on the future enable consideration of how to maintain or
      improve the qualities of a destination. The paper is focused on an analysis of
      the impacts of the energy and ecological macro environments on tourism trends in
      21st century. Mass international tourism has thrived on the abundant and cheap
      supply of energy, and this may be about to change as the world moves towards
      'Peak Oil'. The resultant scarcity and high price of all energy fuels will
      produce changes in human activities, specifically in tourism. The basis of the
      health of the economy is the health of the environment. Therefore issues of
      global environmental changes are increasingly influencing consideration of trends
      in tourism. In this looming transitional era tourism needs to make some dramatic
      changes to harmonize with the new realities of a post-energy world affected
      additionaly by global warming and other environmental changes.

PMID- 22856268
TI  - Opening the dialogue on access to care.

PMID- 22856269
TI  - Common management errors.

PMID- 22856270
TI  - Top 10 ways to guarantee a lawsuit: PLUS #11.

PMID- 22856271
TI  - Social media in the health care provider office.

PMID- 22856272
TI  - Social media marketing still subject to advertising rules.

PMID- 22856273
TI  - Improving access to oral health care in Florida.
AB  - It is the position of the Florida Dental Association that every Floridian should
      understand that good oral health is important to overall health and well-being.
      Good oral health does not just happen; it is the result of both personal
      responsibility and professional care. The great majority of Floridians (more than
      70 percent) receive high quality dental care. Unfortunately, that is not where
      the story of Florida's oral health ends. For the other approximate 30 percent of
      Floridians, the system is broken. Only 23.5 percent of Medicaid enrolled children
      and 11 percent of Medicaid adults receive any dental care annually. This White
      Paper explains the barriers to accessing dental care in Florida, what is
      currently being done to address the problem, and what solutions exist that, if
      implemented in totality, could improve the oral health of millions Floridians.
      Lack of access to care is the result of many factors, including patients'
      preceived need for care, lack of oral health literacy, geographic distribution of
      dentists and dental teams, financial support for care and transportation
      challenges to name a few. It is important that government, dental professionals,
      and advocates work together to identify and address the many barriers to access
      to care.

PMID- 22856274
TI  - Managing dental erosion.
AB  - The clinical signs of dental erosion are initially subtle, yet often progress
      because the patient remains asymptomatic, unaware and uninformed. Erosion
      typically works synergistically with abrasion and attrition to cause loss of
      tooth structure, making diagnosis and management complex. The purpose of this
      article is to outline clinical examples of patients with dental erosion that
      highlight the strategy of early identification, patient education and
      conservative restorative management. Dental erosion is defined as the pathologic
      chronic loss of dental hard tissues as a result of the chemical influence of
      exogenous or endogenous acids without bacterial involvement. Like caries or
      periodontal disease, erosion has a multifactorial etiology and requires a
      thorough history and examination for diagnosis. It also requires patient
      understanding and compliance for improved outcomes. Erosion can affect the loss
      of tooth structure in isolation of other cofactors, but most often works in
      synergy with abrasion and attrition in the loss of tooth structure (Table 1).
      Although erosion is thought to be an underlying etiology of dentin sensitivity,
      erosion and loss of tooth structure often occurs with few symptoms. The purpose
      of this article is threefold: first, to outline existing barriers that may limit
      early management of dental erosion. Second, to review the clinical assessment
      required to establish a diagnosis of erosion. And third, to outline clinical
      examples that review options to restore lost tooth structure. The authors have
      included illustrations they hope will be used to improve patient understanding
      and motivation in the early management of dental erosion.

PMID- 22856275
TI  - Diagnostic discussion: lymphoma.

PMID- 22856276
TI  - Risks and benefits of electronic dental records.

PMID- 22856277
TI  - I got it again. I got it B.A.D.D.

PMID- 22856278
TI  - Weakly electric fish for biomonitoring water quality.
AB  - Environmental pollution is a major issue that calls for suitable monitoring
      systems. The number of possible pollutants of municipal and industrial water
      grows annually as new chemicals are developed. Technical devices for pollutant
      detection are constructed in a way to detect a specific and known array of
      pollutants. Biological systems react to lethal or non-lethal environmental
      changes without pre-adjustment, and a wide variety have been employed as broad
      range monitors for water quality. Weakly electric fish have proven particularly
      useful for the purpose of biomonitoring municipal and industrial waters. The
      frequency of their electric organ discharges directly correlates with the quality
      of the surrounding water and, in this way, concentrations of toxicants down to
      the nanomolar range have been successfully detected by these organisms. We have
      reviewed the literature on biomonitoring studies to date, comparing advantages
      and disadvantages of this test system and summarizing the lowest concentrations
      of various toxicants tested. Eighteen publications were identified investigating
      35 different chemical substances and using six different species of weakly
      electric fish.

PMID- 22856279
TI  - Comparative study of the degradation of carbamazepine in water by advanced
      oxidation processes.
AB  - Degradation of carbamazepine (CBZ) using ultraviolet (UV), UV/H2O2, Fenton,
      UV/Fenton and photocatalytic oxidation with TiO2 (UV/TiO2) was studied in
      deionized water. The five different oxidation processes were compared for the
      removal kinetics of CBZ. The results showed that all the processes followed
      pseudo-first-order kinetics. The direct photolysis (UV alone) was found to be
      less effective than UV/H2O2 oxidation for the degradation of CBZ. An approximate
      20% increase in the CBZ removal efficiency occurred with the UV/Fenton reaction
      as compared with the Fenton oxidation. In the UV/TiO2 system, the kinetics of CBZ
      degradation in the presence of different concentrations of TiO2 followed the
      pseudo-first order degradation, which was consistent with the Langmuir
      Hinshelwood (L-H) model. On a time basis, the degradation efficiencies ofCBZ were
      in the following order: UV/Fenton (86.9% +/- 1.7%) > UV/TiO2 (70.4% +/- 4.2%) >
      Fenton (67.8% +/- 2.6%) > UV/H2O2 (40.65 +/- 5.1%) > UV (12.2% +/- 1.4%).
      However, the lowest cost was obtained with the Fenton process.

PMID- 22856280
TI  - Using D-optimal experimental design to optimise remazol black B mineralisation by
      Fenton-like peroxidation.
AB  - The mineralisation of remazol black B (RBB) was studied at concentrations ranging
      from 20-1000 mgL(-1). The work was aimed at investigating the Fenton-like
      peroxidation of RBB at a concentration typically obtained in Batik cottage
      industries. Other response parameters were degradation and colour removal
      efficiencies. The parameters that were measured included total organic carbon
      (TOC), chemical oxygen demand (COD) as well as absorbance for mineralisation,
      degradation and colour. To optimise the process, the interaction effects of
      several controlling variables on the treatment process were examined using
      dispersion matrix-optimal design and response surface analysis. Four specific
      variables: initial dye concentration (Dye)o; the molar ratio of oxidant to dye
      organic strength (H2O2):(COD); the mass ratio of the oxidant to the catalyst
      (H2O2):(Fe3+) and reaction time (t(r)), were observed. Three reduced empirical
      models, one for each response, were developed for describing the treatment
      process. For 20, 510 and 1000 mgL(-1), the optimum %TOC reduction and oxidation
      times were 44% for 95 min, 52% for 52.5 min and 68% for 10 min corresponding to
      67, 81 and 75% COD reduction, respectively. The optimum COD reduction and
      oxidation times were 89% for 95 min, 91% for 10 min and 84% for 95 min for
      concentrations of 20, 510 and 1000 mg L(-1), respectively. For all
      concentrations, total colour removal was achieved. A comparison of the results
      obtained in this study with literature values for traditional Fenton, photo
      Fenton and photo-Fenton-like oxidation indicated that the TOC reduction obtained
      using the Fenton-like process was satisfactory.

PMID- 22856281
TI  - Removal of toxic metals from aqueous effluents by electrodeposition in a spouted
      bed electrochemical reactor.
AB  - This work investigates the removal of metal ions from synthetic aqueous effluents
      using a spouted bed electrochemical reactor whose cathode was composed of 1.0 mm
      copper particles. Using a Box-Behnken factorial design, the effects of current
      (I), electrode thickness (L), draught distance (d) and support electrolyte
      concentration (C(s)) on current efficiency (CE), space-time yield (Y) and energy
      consumption (EC) were analysed. The results were statistically analysed and the
      effect of each variable was evaluated using the surface response methodology. The
      results showed that C(s) is the most important variable to consider in the
      process optimization. A current of 8.0 A can be applied in order to obtain high Y
      and CE with an acceptable EC. Electrode thicknesses greater than 1.3 cm are not
      recommended because the irregular potential distribution leads to a Y drop owing
      to the low CE observed for this condition. The draught distance does not have
      statistical significance; therefore, the particle circulation rate is not
      important in this kind of electrochemical reactor.

PMID- 22856282
TI  - Applying real-time control for achieving nitrogen removal via nitrite in a lab
      scale CAST system.
AB  - In this study, a bench-scale Cyclic Activated Sludge Technology (CAST) reactor
      (72?L), fed with domestic sewage, was operated in alternating anoxi-aerobic
      operation mode to investigate the feasibility of achieving short-cut
      nitrification and denitrification with a real-time control strategy. An online
      system for controlling the length of the aeration and stirring phases was
      implemented, based on pH and oxidation-reduction potential signals, to switch
      between aerobic and anoxic sequences. Results show that the real-time control
      strategy was successful in achieving a stable nitrogen removal performance.
      Furthermore, short-cut nitrification can be achieved by controlling aeration
      length under the modified real-time control strategy. Gradually reducing the
      energy supply for nitrite-oxidizing bacteria caused the limitation of their
      growth and, finally, their elimination. When short-cut nitrification was
      obtained, the nitrite pathway became the primary way for nitrogen removal, and
      aeration duration was reduced by 28.4%.

PMID- 22856283
TI  - Effect of organic carbon on nitrogen conversion and microbial communities in the
      completely autotrophic nitrogen removal process.
AB  - Two identical SBBRs (sequencing batch biofilm reactors) were monitored to
      evaluate the effects of organic carbon (OC) on nitrogen conversion and microbial
      communities. In the organic-fed reactor, an ammonium conversion efficiency of
      above 99%, TN (total nitrogen) removal efficiency of 84-95% and COD (chemical
      oxygen demand) removal efficiency of about 90% were obtained at a C/N ratio of
      1.2. In the OC-fed reactor, the contribution of partial nitrification-anammox to
      nitrogen removal decreased to 50.78%, and the contribution of denitrification
      increased to 49.22%. Denaturing gradient gel electrophoresis profiles showed an
      intensified bacterial diversity and an enrichment of Planctomycetes bacteria due
      to the presence of OC particularly in the biofilm. Clone library analysis
      revealed the coexistence of denitrifiers, aerobic ammonium oxidizers, and anammox
      bacteria in the OC-fed reactor.

PMID- 22856284
TI  - Municipal wastewater treatment in Mexico: current status and opportunities for
      employing ecological treatment systems.
AB  - The aim of this paper is to evaluate the current status of municipal wastewater
      (MWW) treatment in Mexico, as well as to assess opportunities for using
      ecological treatment systems, such as constructed wetlands. In 2008, Mexico had
      2101 MWW treatment plants that treated only 84 m3/s of wastewater (208 m3/s ofMWW
      were collected in sewer systems). Unfortunately, most treatment plants operate
      below capacity owing to a lack of maintenance and paucity of properly trained
      personnel. The main types of treatment systems applied in Mexico are activated
      sludge and waste stabilization ponds, which treat 44.3% and 18% of the MWW
      collected, respectively. As in many other developing nations around the world,
      there is a great need in Mexico for low-cost, low-maintenance wastewater
      treatment systems that are both economically and environmentally sustainable. In
      2005, 24.3 million Mexicans lived in villages of less than 2500 inhabitants and
      14.1 million lived in towns with 2500-15,000 inhabitants. An opportunity exists
      to extend the use of ecological treatment systems to these low population density
      areas and considerably increase the percentage of MWW that is treated in Mexico.
      Small-scale and medium-size constructed wetlands have been built successfully in
      some states, primarily during the past five years. Several barriers need to be
      overcome to increase the adoption and utilization of ecological wastewater
      technology in Mexico, including: a lack of knowledge about this technology,
      scarce technical information in Spanish, and the government's concentration on
      constructing MWW treatment plants solely in urban areas.

PMID- 22856285
TI  - Wastewater from wood and pulp industry treated by combination of coagulation,
      adsorption on modified clinoptilolite tuff and membrane processes.
AB  - Wastewater from the wood and pulp industry is of environmental concern. It
      contains high concentrations of organic and inorganic matter. In this work a
      combined method of coagulation, adsorption and nanofiltration/reverse osmosis
      (NF/RO) was investigated in the purification of biologically treated wastewater
      from wood processing. Coagulation with 0.8 g dm(-3) AlCl3 x 6H2O and adsorption
      on 2.5 g m(-3) modified clinoptilolite tuff resulted in removal efficiencies of
      total carbon (TC), total organic carbon (TOC) and inorganic carbon (IC) up to
      67.1%, 77.4% and 49.5%, respectively. Almost complete removal of solutes was
      achieved after NF/RO treatment. The TOC removal efficiency with RO membrane (CPA
      3, LFC-1, XLE) and tight NF membrane (NF90) was 98% and with highly porous NF
      membrane (DK), 88%. After the proposed treatment the purified water stream can be
      recycled into the process or safely disposed to the river.

PMID- 22856286
TI  - Killing of total heterotrophic bacteria using the gas diffusion electrode system.
AB  - This study focused on the disinfection of dual electrodes with a gas diffusion
      cathode using total heterotrophic bacteria as indicator microorganisms. Batch
      tests were performed to study the effects of platinum load W(Pt) and the pore
      forming agent content WNH4HCO3 in gas diffusion electrodes on the germicidal
      efficacy eta and H2O2 yield. The results showed that the disinfection improved
      with W(Pt), but its efficiency at W(Pt) of 3 per thousand was equivalent to W(Pt)
      of 4 per thousand. The right amount of the pore-forming agent improved
      disinfection. Continuous tests were performed to study residence times (RTs), pH
      and oxygen flow rates Qo2 on the germicidal efficacy and H2O2 yield. The results
      indicated that at the steady state total heterotrophic bacteria in the outlet
      stream were completely inactivated under our experimental conditions.
      Disinfection improved with increasing RT. This phenomenon was more significant
      when RT < 20 min. A drop in pH value resulted in the rapid rise of germicidal
      efficacy, while disinfection shortened with an increasing oxygen flow rate Qo2.
      The operating costs are high. Further research is required to fully understand
      all parameters and reduce operating costs.

PMID- 22856287
TI  - Thermal decomposition kinetics of Brazilian limestones: effect of CO2 partial
      pressure.
AB  - The influence of the partial pressure of carbon dioxide (CO2) on the thermal
      decomposition process of a calcite (CI) and a dolomite (DP) is investigated in
      this paper using a thermogravimetric analyser. The tests were non-isothermal at
      five different heating rates in dynamic atmosphere of air with 0% and 15% carbon
      dioxide (CO2). In the atmosphere without CO2, the average activation energies
      (E(alpha)) were 197.4 kJ mol(-1) and 188.1 kJ mol(-1) for CI and DP,
      respectively. For the DP with 15% CO2, two decomposition steps were observed,
      indicating a change of mechanism. The values of E(alpha) for 15% CO2 were 378.7
      kJ mol(-1) for the CI, and 299.8 kJ mol(-1) (first decomposition) and 453.4 kJ
      mol(-1) (second decomposition) for the DP, showing that the determination of
      E(alpha) for DP should in this case be considered separately in those two
      distinct regions. The results obtained in this study are relevant to
      understanding the behaviour changes in the thermal decomposition of limestones
      with CO2 partial pressure when applied to technologies, such as carbon capture
      and storage (CCS), in which carbon dioxide is present in high concentrations.

PMID- 22856289
TI  - Dissolution kinetics of quicklime in various organic solvents and solutions.
AB  - The rate of the dissolution of quicklime was measured in different organic
      solvents and solutions of methanol, ethylene glycol, glycerol and sucrose. It was
      found that the rate of dissolution in methanol, glycerol and sucrose was
      dramatically reduced compared with that in deionized water. However, little
      difference was measured in a solution of ethylene glycol compared with aqueous
      solutions. The presence of chloride ions increases the rate of dissolution in all
      solvents and solutions, except for ethylene glycol, where a decrease was actually
      observed. It was also found that the presence of sulphate ions decreases the rate
      in all organic solvents and solutions tested.

PMID- 22856288
TI  - Enhanced photodegradation of o-cresol in aqueous Mn(1%)-doped ZnO suspensions.
AB  - The effective removal of o-cresol is currently both an environmental and economic
      challenge. ZnO is not only an efficient photocatalyst but is also cost effective,
      as its photoabsorption can extend from the ultraviolet (UV) to the visible range
      thereby allowing the use of inexpensive visible light sources, such as sunlight.
      The principal objective of the present work is to investigate the visible light
      driven removal of o-cresol from aqueous solution in the presence of 1.0 wt% Mn
      doped ZnO. To measure the efficiency ofphotodegradation, the variables studied
      included the amount ofphotocatalyst, concentration of o-cresol, pH and
      irradiation time. The concentration ofo-cresol and residual organic carbon was
      monitored using a UV-visible spectrophotometer, ultra high-pressure liquid
      chromatography and a total organic carbon analyser. The optimum conditions under
      which the photodegradation of o-cresol was most favourable corresponded to 1.5
      g/l ZnO, 35 ppm o-cresol and pH 9. The ZnO-1 wt% Mn photoprocess has demonstrated
      reusability for more than three times, which warrants its scale-up from
      laboratory- to in industrial-scale application.

PMID- 22856290
TI  - Experimental investigation on consistency limits of cement and lime-stabilized
      marine sediments.
AB  - This paper presents the effects of treatments with cement and lime on the
      consistency limits of marine sediments dredged from Dunkirk port. The Casagrande
      percussion test and the fall cone test were used to determine the liquid limits
      of raw sediments and treated marine sediments. For the evaluation of the plastic
      limits, the results of the fall cone test were compared with those obtained by
      the rolling test method. The relationship between the water contents and the
      penetration depths for the determination of the liquid limit and the plastic
      limit was explored. Liquid limits at 15.5 mm and plastic limits at 1.55 mm seem
      to be a more appropriate choice for the studied marine sediments compared with
      the limits determined by other used prediction methods. Finally, the effect of
      cement treatment and lime treatment on the Casagrande classification of the
      studied sediments was investigated according to the different prediction results.

PMID- 22856291
TI  - Evaluation of hydrogen sulphide concentration and control in a sewer system.
AB  - This study focused on monitoring hydrogen sulphide (dissolved and atmospheric)
      generation and wastewater volumetric flow in a 21.4 km sewer line of the City of
      San Antonio, Texas. The results were used to evaluate daily and seasonal trends
      of atmospheric and dissolved sulphide, and to better apply sulphide control using
      ferrous sulphate to prevent odour and sewer pipe deterioration. As part of this
      study, the evaluation of a cost-effective dosing strategy with ferrous sulphate
      was performed to better control the sulphide contents in wastewater. Dosing
      studies were performed in the laboratory to find the required ratio of ferrous
      sulphate for acceptable sulphide removal. The results indicate a 1.25 mole ratio
      requirement, to reduce sulphide by 93%. Over a typical daily diurnal cycle,
      necessary dosing rates to maintain sulphide concentrations below 2mg varied
      between 0 and 36,777 mold(-1) with a daily average rate of 14,438 mol d(-1). If,
      instead of dosing at the maximum required rate, dosing was matched over the
      diurnal cycle, chemical savings would amount to 22,339 mold(-1) while achieving
      sulphide control. The approximate cost of the ferrous sulphate solution dosed is
      $0.14 per mol and this amount of chemical savings translates into roughly $2923
      per day. Actual dosing cost for the hypothetical average day will be $1889 per
      day. These cost savings can easily recoup the required instrumentation costs to
      achieve this diurnal dose matching.

PMID- 22856292
TI  - Partial oxidative gasification of municipal sludge in subcritical and
      supercritical water.
AB  - Subcritical and supercritical water gasification of dewatered sewage sludge
      obtained from a typical municipal wastewater treatment plant was investigated in
      a one-litre high-pressure autoclave at temperatures of 300-400 degrees C and
      pressures of 17.5-23.5 MPa. The sludge (without catalyst) was gasified at
      subcritical and supercritical water conditions, with different reaction times
      ranging from 30 to 60 min. The results showed that gaseous product yield
      increased with increasing temperature and reaction time. Gas products consisted
      primarily of hydrogen, carbon dioxide, methane, carbon monoxide and other light
      hydrocarbons. The liquid products contained high levels of organic matter,
      ammonia nitrogen and a few heavy metals. Compared with the landfilling of sewage
      sludge, the solid residues were in accordance with the Chinese standard for
      sludge quality in co-landfilling even without further treatment. In addition, the
      heavy metals in solid products exhibited more stable characteristics attributable
      to the reduced leaching toxicity after supercritical water gasification.

PMID- 22856293
TI  - Advances on simultaneous desulfurization and denitrification using activated
      carbon irradiated by microwaves.
AB  - This paper describes the research background and chemistry of desulfurization and
      denitrification technology using microwave irradiation. Microwave-induced
      catalysis combined with activated carbon adsorption and reduction can reduce
      nitric oxide to nitrogen and sulfur dioxide to sulfur from flue gas effectively.
      This paper also highlights the main drawbacks of this technology and discusses
      future development trends. It is reported that the removal of sulfur dioxide and
      nitric oxide using microwave irradiation has broad prospects for development in
      the field of air pollution control.

PMID- 22856294
TI  - Isolation and characterization of pullulan-degrading Anoxybacillus species
      isolated from Malaysian hot springs.
AB  - Two thermophilic bacteria (SK3-4 and DT3-1) were isolated from the Sungai Klah
      (SK) and Dusun Tua (DT) hot springs in Malaysia. The cells from both strains were
      rod-shaped, stained Gram positive and formed endospores. The optimal growth of
      both strains was observed at 55 degrees C and pH 7. Strain DT3-1 exhibited a
      higher tolerance to chloramphenicol (100 microg ml(-1)) but showed a lower
      tolerance to sodium chloride (2%, w/v) compared to strain SK3-4. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that both strains belong to
      the genus Anoxybacillus. High concentrations of 15:0 iso in the fatty acid
      profiles support the conclusion that both strains belong to the genus
      Anoxybacillus and exhibit unique fatty acid compositions and percentages compared
      to other Anoxybacillus species. The DNA G + C contents were 42.0 mol% and 41.8
      mol% for strains SK3-4 and DT3-1, respectively. Strains SK3-4 and DT3-1 were able
      to degrade pullulan and to produce maltotriose and glucose, respectively, as
      their main end products. Based on phenotypic and chemotaxonomic characteristics,
      16S rRNA gene sequences, and the DNA G + C content, we propose that strains SK3-4
      and DT3-1 are new pullulan-degrading Anoxybacillus strains.

PMID- 22856295
TI  - An investigation on the sorption behaviour of montmorillonite for selected
      organochlorine pesticides from water.
AB  - The sorption behaviour of montmorillonite towards organochlorine pesticides
      (OCPs) from aqueous solutions is reported. After preliminary investigation of the
      sorption capability of clay for selected OCPs, aldrin was used as a model
      compound for further experiments. The batch sorption experiments were carried out
      as functions of contact time, pH of the solution, initial aldrin concentration
      and dosage of the montmorillonite. After traditional liquid-liquid extraction,
      the determination of OCPs was carried out by gas chromatography coupled with a
      micro-electron capture detector (GC-microECD). The results indicated that
      sorption of aldrin followed the second-order kinetic model and that the
      equilibrium time depended on the initial aldrin concentration. The film diffusion
      was found to be a main sorption rate control mechanism. The removal was explained
      according to the electrostatic bonding mechanism. The Freundlich isotherm model
      better represented the sorption data than the Langmuir model. The montmorillonite
      was also used efficiently for the removal of OCPs from fortified tap and surface
      (lake) water samples.

PMID- 22856296
TI  - Simultaneous removal of ammonium and suspended solids in multipurpose filters.
AB  - A multipurpose filter in which sand and clinoptilolite are used together as
      filter material is suggested for the simultaneous removal of suspended solids and
      ammonium in one single unit. The capacity of the clinoptilolite used was
      determined as 10.4 mg/g for 20 mg/l initial ammonium concentration. In addition,
      a packed column ion exchanger with clinoptilolite and a classical sand filter
      were also investigated for comparison. Ammonium and suspended solids removal
      rates were observed and compared for all columns. The results of the column
      analysis have revealed that the ammonium removal rate, which was only 20% in the
      sand column, was increased to 100% by replacing 50% of the sand with
      clinoptilolite; similarly, the suspended solids removal, which was only 17% in
      the clinoptilolite column, was increased to 75% by replacing 50% of the
      clinoptilolite with sand. As such, when ion exchange and filtration processes
      were carried out in a multipurpose column, high removals for both parameters
      could be obtained simultaneously. Multipurpose columns could be an alternative
      both for the upgrading of existing treatment plants or for new plants for
      simultaneous removal of ammonium and suspended solids, giving considerable
      savings in terms of land requirements.

PMID- 22856297
TI  - Depuration in aerated ponds of citrus processing wastewater with a high
      concentration of essential oils.
AB  - Citrus processing wastewater was treated in aerated pilot plants in order to
      evaluate the following: (a) energy efficiency under different air flow rates and
      times; and (b) limits of spontaneous microflora in adapting to essential oils. In
      comparison to permanent air flow, night aeration for 12 hours determined an
      increase of up to 12% of the monthly removal rate of chemical oxygen demand (COD)
      and a consequent reduction by 10% of energy consumptions per unit of COD removed
      from 0.63 to 0.57 kWh/kg(COD). Lowering night aeration from 14 to 7 1/m3/h
      reduced by only 10% the removal rate of COD; the energy consumption per unit of
      COD removed (0.32 kWh/kg(COD)) was consequently reduced by more than 40%.
      Dissolved oxygen was maintained at very low level, rarely exceeding 0.2 ppm, with
      no bad smell. The consequent high oxygen deficit of 98-99% of saturation induced
      high oxygen transfer efficiency. The microbial population was characterized
      mainly by aerobic bacteria; only 5-8% of bacteria were strictly anaerobic. In the
      deep tank layer under the air diffuser a small amount of sludge settled (0.03
      0.04 kg of dry matter per kg of COD removed), containing only 3% of total organic
      matter detected at the end of the depuration process. The fact that the
      concentration of essential oils could be progressively increased up to 1400 ppm
      without noticeably slowing down the biological processes demonstrated the
      remarkable microbial adaptation.

PMID- 22856298
TI  - Kinetic analysis of an anaerobic fixed-film fixed bed-reactor treating wastewater
      arising from production of a chemically synthesized pharmaceutical.
AB  - The kinetics of the treatment of a pharmaceutical wastewater (PW), pretreated in
      a first stage by electrocaogulation (EC), using an anaerobic fixed-film fixed-bed
      reactor was investigated. The experimental results for the substrate removal
      kinetics were found to be in good agreement with those of the Monod model and the
      modified Stover-Kincannon model, with a high regression value (R2 > 0.9). For the
      modified Stover-Kincannon model, the constants U(max), and K(B) were found to be
      13.1 and 13.87 kg COD/(m3 x d) respectively. With reference to the biomass
      kinetics, the increase in organic loading rate (OLR) is attributed to the
      increased biomass growth rate (micro) and decrease in the biological constant
      K(micro). The corresponding constants for the modified Monod's model, i.e.
      'micro(max) and decay constant K(d), were found to be 0.159 and 0.0113 d(-)1
      respectively. Finally, the gas production kinetics was interpreted in relation to
      the Kincannon-Stover model.

PMID- 22856299
TI  - Nitrification and denitrification using biofilters packed with sulfur and
      limestone at a pilot-scale municipal wastewater treatment plant.
AB  - A pilot-scale municipal wastewater treatment plant composed of a fixed film
      activated sludge (IFAS) system with sulfur-limestone autotrophic denitrification
      (SLAD) was operated for a year and the influence of different operational factors
      was investigated. Nitrification efficiency was found to be above 91% at
      temperatures above 25 degrees C even at short hydraulic residence times (HRTs),
      but declined to 51 +/- 2% when the temperature dropped to 22 +/- 3 degrees C. The
      minimum HRT (HRT(min)) to achieve nitrification efficiency > 90% was found to be
      12 h at temperatures above 25 degrees C. Denitrification efficiencies were found
      to be 89% and 79% at a nitrate loading of 0.36 kg NO3(-)-N m(-3) d(-1) and at
      0.18 kg NO3(-)-N m(-3) d(-1), respectively. The minimum empty bed residence time
      (EBRT) to achieve denitrification efficiency above 80% without methanol addition
      was 3 h at a nitrate loading rate of 0.27-0.38 kg NO3(-)-N m(-3) d(-1). The
      amount of nitrate removed as a function of the sulfate formed was found to be
      0.188 g NO3(-)-N/g SO4(2-). The nitrate load removed by the biofilter as a
      function of the alkalinity consumed was found to be very close to the theoretical
      stoichiometric value. The application of the pilot plant was proven to be
      feasible and the performance of the SLAD system, especially with respect to the
      minimum EBRT to achieve denitrification efficiency above 80%, the maximum
      denitrification rate and performance at temperatures below 10 degrees C. To
      achieve a nitrification efficiency above 90% in the IFAS system, temperature
      changes and the minimum HRT were found to be the most influential operational
      parameters.

PMID- 22856300
TI  - Removal of diclofenac potassium from wastewater using clay-micelle complex.
AB  - The presence of an ionized carboxyl group in the widely used non-steroidal anti
      inflammatory (NSAID) drug diclofenac potassium results in a high mobility of
      diclofenac and in its low sorption under conditions of slow sand filtration or
      subsoil passage. No diclofenac degradation was detected in pure water or sludge
      during one month. Tertiary treatments of wastewater indicated that the effective
      removal of diclofenac was by reverse osmosis, but the removal by activated carbon
      was less satisfactory. This study presents an efficient method for the removal of
      diclofenac from water by micelle-clay composites that are positively charged,
      have a large surface area and include large hydrophobic domains. Adsorption of
      diclofenac in dispersion by charcoal and a composite micelle
      (otadecyltrimethylammonium [ODTMA] and clay [montmorillonite]) was investigated.
      Analysis by the Langmuir isotherm revealed that charcoal had a somewhat larger
      number of adsorption sites than the composite, but the latter had a significantly
      larger binding affinity for diclofenac. Filtration experiments on a solution
      containing 300 ppm diclofenac demonstrated poor removal by activated carbon, in
      contrast to very efficient removal by micelle-clay filters. In the latter case
      the weight of removed diclofenac exceeded half that of ODTMA in the filter.
      Filtration of diclofenac solutions at concentrations of 8 and 80 ppb yielded
      almost complete removal at flow rates of 30 and 60 mL min(-1). One kilogram of
      ODTMA in the micelle-clay filter has been estimated to remove more than 99% of
      diclofenac from a solution of 100 ppb during passage of more than 100 m3.

PMID- 22856301
TI  - Aeration efficiency influenced by venturi aerator arrangement, liquid flow rate
      and depth of diffusing pipes.
AB  - The effect of aerator module configuration, liquid flow rate and diffuser
      submergence on oxygen transfer efficiency was examined in a surface aeration
      system with venturi injectors using the clean water test. Six venturi aerator
      modules were evaluated and the results indicated that better aeration
      efficiencies could be achieved by simply changing the way the venturi aerators
      were connected. Among all the configurations examined (modules a-f), two and
      three aerators connected in parallel (modules d, e and f) were able to bring more
      oxygen into water than the others. An increase in liquid flow rate led to an
      enhancement of the oxygen transfer coefficients, but the improvement was reduced
      if the liquid flow rate was too high. The oxygen transfer coefficient was found
      to have a relationship with the depth of diffusing pipes (surface aeration depth)
      for the surface aeration system and an optimal depth of around 40 cm was obtained
      from this study.

PMID- 22856302
TI  - Removal of BTEX from aqueous solution using Moringa oleifera seed cake.
AB  - In this study, the removal of BTEX (benzene, toluene, ethylbenzene, p-xylene and
      o-xylene) from aqueous solution using Moringa oleifera seed cake (MOSC) was
      investigated. The effect of parameters such as contact time, pH and initial BTEX
      concentration were studied to optimize the conditions for maximum removal.
      Maximum removal values of 75 +/- 1%, 85 +/- 2%, 86 +/- 2%, 88 +/- 2% and 87 +/-
      1% were obtained for benzene, toluene, ethylbenzene, p-xylene and o-xylene,
      respectively, at pH 7.0, with a 20 min contact time for an adsorbent dose of 10 g
      L(-1) of 1 mg L(-1) BTEX concentration. The adsorption data fitted the Langmuir
      and Freundlich adsorption isotherms. The capacity of MOSC to adsorb BTEX was
      compared with that for a commercial activated carbon. The results from the two
      methods were not significantly different (judged by t-test at 95% confident
      interval). A low cost, easy purchase and the satisfactory experimental results
      indicated that MOSC is a promising natural material for the removal of BTEX from
      aqueous solution.

PMID- 22856303
TI  - Manganese-electrolysed slag treatment: bioleaching of manganese by Fusarium sp.
AB  - A fungi strain named Fusarium sp. was isolated from manganese-electrolysed slag
      by using a gradient dilution spread plate method, identified by 26S RNA sequence
      analysis and phylogenetic tree analysis, and explored for the bioleaching
      capacity to manganese (II) from manganese-electrolysed slag in liquid mineral
      medium under different environmental conditions, including system temperature,
      incubator rotation speed and initial pH value. DNA sequence and phylogenetic
      analysis indicated the name of this fungi strain, that is, Fusarium sp., and
      higher bioleaching efficiencies (71.6%) of manganese by this fungi were observed
      when the bioleaching was carried out under the optimized conditions as follows:
      contact time: 72 h; system temperature: 28 degrees C; inoculums concentration: 2%
      (v/v); incubator rotation speed: 150 rpm; pH 4.0. Because of its low cost,
      environment friendliness and better efficiency, the bioleaching technique will
      have a significant impact on manganese-electrolysed slag pollution mitigation.

PMID- 22856304
TI  - Feasibility of manufacturing geopolymer bricks using circulating fluidized bed
      combustion bottom ash.
AB  - This paper presents a study on geopolymer bricks manufactured using bottom ash
      from circulating fluidized bed combustion (CFBC). The alkali activators used for
      synthesis were sodium silicate, sodium hydroxide, and potassium hydroxide and
      lithium hydroxide solutions. The study included the impact of alkali activator on
      compressive strength. The reaction products were analysed by XRD, FT-IR and
      SEM/EDS. The compressive strength of bricks was dependent on the modulus of the
      sodium silicate activator and the type and concentration of alkali activator. The
      highest compressive strength could be gained when the modulus was 1.5, and the
      value could reach 16.1 MPa (7 d after manufacture) and 21.9 MPa (28 d after
      manufacture). Under pure alkaline systems, the compressive strength was in the
      order of 10 M KOH > 10 M NaOH > 5 M LiOH > 5 M KOH > 5 M NaOH. Quartz was the
      only crystalline phase in the original bottom ash, and no new crystalline phase
      was found after the reaction. The main product of reaction was amorphous alkali
      aluminosilicate gel and a small amount of crystalline phase was also found by
      SEM.

PMID- 22856305
TI  - Efficiency of subsurface flow constructed wetland with trickling filter.
AB  - Effective wastewater purification in subsurface flow constructed wetlands must
      include adequate pretreatment and ensure a sufficient amount of dissolved oxygen.
      In a pilot-scale operation, a subsurface flow constructed wetland (CW) consisted
      of a primary settlement tank, a trickling filter for pretreatment and two
      serially assembled basins. The trickling filter was added to ensure sufficient
      aeration, increase purification of the wastewater and shorten the wastewater
      purification time. The estimated nominal flow was 0.7 m3/d. The experiments were
      conducted using the wastewater from the municipal sewage canal of the city of
      Zagreb, with utilization of three different flows: 0.72 (A), 1.44 (B) and 2.88
      (C) m3/d. The efficiency of the purification process was monitored over a period
      of three years (TSS, BOD5, COD, NH4-N, NO2-N, PO4-P, dissolved oxygen,
      temperature and pH). The experimental results showed an increase in the removal
      efficiency with a doubling of the nominal flow from 0.7 to 1.44 m3/d, which could
      be related to the implementation of the trickling filter where high removal rates
      were achieved.

PMID- 22856306
TI  - Selective catalytic reduction (SCR) of NO by urea loaded on activated carbon
      fibre (ACF) and CeO2/ACF at 30 degrees C: the SCR mechanism.
AB  - Selective catalytic reduction (SCR) of NO by urea loaded on rayon-based activated
      carbon fibre (ACF) and CeO2/ACF (CA) was studied at ambient temperature (30
      degrees C) to establish a basic scheme for its reduction. Nitric oxide was found
      to be reduced to N2 with urea deposited on the ACF and CA. When oxygen was
      present, the greater the amount of loaded urea (20-60%), the greater the NO(x)
      conversions, which were between 72.03% and 77.30%, whereas the NO(x) conversions
      were about 50% when oxygen was absent. Moreover, when the urea was loaded on CA,
      a catalyst containing 40% urea/ACF loaded with 10% CeO2 (UCA4) could yield a
      NO(x) conversion of about 80% for 24.5 h. Based on the experimental results, the
      catalytic mechanisms of SCR with and without oxygen are discussed. The enhancing
      effect of oxygen resulted from the oxidation of NO to NO2, and urea was the main
      reducing agent in the SCR of loaded catalysts. ACF-C was the catalytic centre in
      the SCR of NO of ACF, while CeO2 of urea-loaded CA was the catalytic centre.

PMID- 22856307
TI  - Catalytic behaviour and copper leaching of Cu0.10Zn0.90Al1.90Fe0.10O4 spinel for
      catalytic wet air oxidation of phenol.
AB  - A Cu0.10Zn0.90Al1.90Fe0.10O4 spinel catalyst prepared by the sol-gel method was
      tested for catalytic wet air oxidation (CWAO) of phenol. The catalyst showed high
      activity for phenol degradation. During successive test at 170 degrees C, 100%
      phenol conversion and 95% chemical oxygen demand (COD) removal were observed.
      Results from scanning electron microscopy (SEM), Fourier transform infrared
      spectroscopy (FT-IR) and X-ray diffraction (XRD) indicated that the catalyst
      structure remained unchanged during reaction. From the analysis of temperature
      programmed reduction (TPR), diffuse reflectance UV-Vis spectra (DR UV-Vis) and
      activity assay at basic solution pH, it can be suggested that the highly
      dispersed copper ions on the catalyst surface were almost completely dissolved
      into the reaction solution, whereas the tetra-coordinated copper ions were not
      only stable against leaching but also active towards phenol degradation.

PMID- 22856308
TI  - Adsorption of phosphate from aqueous solution by hydrous zirconium oxide.
AB  - Synthetic ZrO2 x nH2O was used for phosphate removal from aqueous solution. The
      optimum adsorbent dose obtained for phosphate adsorption on to hydrous zirconium
      oxide was 0.1 g. The kinetic process was described very well by a pseudo-second
      order rate model. The phosphate adsorption tended to increase with the decrease
      in pH. The adsorption capacity increased from 61 to 66 mg g(-1) when the
      temperature was increased from 298 to 338 K. A phosphate desorption of
      approximately 74% was obtained using water at pH 12.

PMID- 22856309
TI  - Effect of membrane properties on the performance of a hybrid GAC and
      ultrafiltration process for water treatment.
AB  - The performance of a hybrid granular activated carbon (GAC) and ultrafiltration
      (UF) process for water treatment was investigated using five types of UF
      membranes. The removal percentages for chemical oxygen demand (COD(Mn)),
      particles (> or = 2 microm) and total bacteria by the hybrid process were 30-40%,
      98-99% and 76-92%, respectively. No invertebrates were detected in the hybrid
      process effluent. Transmembrane pressure and specific permeate flux (SPF) of the
      five types of membranes varied. With decreasing membrane pore sizes, removal of
      COD(Mn) and particles increased, whereas SPF firstly decreased and then
      increased. Hydrophilic membranes had a relatively high COD(Mn) removal potential,
      but did not obviously affect particle removal or SPF.

PMID- 22856310
TI  - Fast start-up and controlled operation during a long-term period of a high-rate
      partial nitrification activated sludge system.
AB  - Partial nitrification of a high-strength ammonium wastewater (1150 +/- 150 mg N
      NH4(+) L(-1)), mimicking reject water, was achieved in an activated sludge pilot
      plant with a configuration of three continuous reactors in series plus a settler.
      Stable and robust partial nitrification was maintained during 800 days of
      operation at 30 degrees C with a sludge retention time (SRT) of 8 +/- 3 days. A
      high volumetric ammonium oxidation rate (2.0 g N L(-1) d(-1)) was obtained with a
      [N-NO2-]/[N-NO(x)-] ratio of 1, i.e. full nitritation. The start-up of the
      partial nitrification system was quickly and successfully performed with an on
      line control system using municipal wastewater treatment plant (WWTP) sludge as
      inoculum. An ammonia-oxidizing bacteria (AOB) fraction of 72 +/- 10% was obtained
      after only 30 days of start-up. The applied SRT of 7-10 days with the combination
      of free ammonia inhibition and dissolved oxygen limitation provided the selective
      washout of nitrite-oxidizing bacteria (NOB) and an active nitrifying population
      with high ammonium oxidizing rates.

PMID- 22856311
TI  - Removal of bisphenol A from aqueous solution by a dodecylsulfate ion-intercalated
      hydrotalcite-like compound.
AB  - A Mg-Al hydrotalcite-like compound (HTlc) and a dodecylsufate ion-intercalated Mg
      Al HTlc (MHTlc) were prepared. The effects of temperature, ionic strength, and
      initial pH on the adsorptions ofbisphenol A (BPA) on both HTlc and MHTlc were
      studied in detail. The adsorption capacity of the pristine HTlc for BPA was low,
      and the adsorption was due to the substitution of surface anions within the
      pristine HTlc by the hydroxybenzene anion that was dissociated from BPA. The
      adsorption capacity for BPA increased notably with modification. The high
      adsorption capacity of MHTlc for BPA was mainly due to the dissolution of BPA
      molecules into the hydrophobic organic phase formed in the interlayers of MHTlc.
      The adsorption capacity of MHTlc for BPA decreased with increasing temperature
      and initial pH, but increased when increasing the ionic strength.

PMID- 22856312
TI  - Effect of phenol and acetate addition on 2-chlorophenol consumption by a
      denitrifying sludge.
AB  - Chlorophenols are widely distributed in the environment. Various strategies have
      been used to improve their biological elimination under anaerobic conditions;
      however, such information is still scarce. The aim of this study was to evaluate
      in batch assays the consumption of 2-chlorophenol (2-CP) by a denitrifying sludge
      and the influence of acetate or phenol as co-substrates in the 2-CP consumption.
      It was observed that phenol (69 and 92 mg phenol-C L(-1)) and acetate (60 and 108
      mg acetate-C L(-1)) enhanced 2-CP consumption by the denitrifying sludge,
      increasing both the efficiency (up to 100%) and specific rate of 2-CP
      consumption. When phenol was added at 92 mg C L(-1), the specific consumption
      rate of 2-CP increased 2.6 times with respect to the control lacking co
      substrates, whereas with acetate (108 mgC L(-1)) the increase was 9.0 times.
      Acetate appeared to be a better co-substrate for 2-CP consumption, obtaining a
      specific consumption rate of 2.48 +/- 0.14 mg 2-CP-C g(-1) VSS d(-1) at 108 mg
      acetate-C L(-1). The mass balance analysis indicated that the denitrifying sludge
      was able to simultaneously mineralize 2-CP, phenol or acetate (E2-CP, E(Phenol),
      and E(Acetate) close to 100% [E = consumption efficiency], Y(HCO3-) of 0.90 +/-
      0.10 [Y = yield]) and reduce nitrate to nitrogen gas (E(NO3-) of 100% and Y(N2)
      of 0.96 +/- 0.02). It was shown that the addition of co-substrates as phenol or
      acetate could be a good alternative for improving the elimination of
      chlorophenols from wastewaters by denitrifying sludges.

PMID- 22856313
TI  - Metal-resistant microorganisms and metal chelators synergistically enhance the
      phytoremediation efficiency of Solanum nigrum L. in Cd- and Pb-contaminated soil.
AB  - The effects of metal-resistant microorganisms and metal chelators on the ability
      of Solanum nigrum L. to accumulate heavy metals were investigated. In the
      presence of multiple metal contaminants (Cd and Pb), citric acid (CA)
      significantly enhanced the biomass and Cd accumulation of S. nigrum, but these
      conditions decreased the accumulation of Pb. Application of Cd- or Pb-resistant
      microorganisms improved the ability of S. nigrum to accumulate heavy metals and
      increased plant yield, but the effects of microorganisms on phytoextraction were
      smaller than the effects of CA. When plants were grown in the presence of Cd
      contamination, the co-application of CA and metal-resistant strains enhanced
      biomass by 30-50% and increased Cd accumulation by 25-35%. However, these
      conditions decreased Pb accumulation in the presence of Pb pollution. S. nigrum
      could tolerate a combination of Cd and Pb pollution. In the presence of CA and
      the metal-resistant microorganisms, the plants were able to acquire 15-25% more
      Cd and 10-15% more Pb than control plants. We propose that the synergistic
      combination of plants, microorganisms and chelators can enhance phytoremediation
      efficiency in the presence of multiple metal contaminants.

PMID- 22856314
TI  - Effect of extraction solutions on carbonation of cementitious materials in
      aqueous solutions.
AB  - Carbonation efficiency was evaluated for three cementitious materials having
      different CaO-bearing minerals (lime, Portland cement and waste concrete) using
      various extraction reagents (HCl, CH3COOH, NH4Cl and deionized water). The
      cementitious materials were subjected to Ca extraction and carbonation tests
      under ambient pressure and temperature conditions. The Ca extraction efficiency
      generally decreased in the order lime, Portland cement and waste concrete,
      regardless of the extraction solution. Among the extraction solutions, NH4Cl was
      the most effective for Ca extraction and carbonation. The results of this study
      suggest that the types of extraction solution and CaO-bearing mineral of the
      materials are primary factors affecting carbonation efficiency.

PMID- 22856315
TI  - Efficiency of a pilot-scale integrated sludge thickening and digestion reactor in
      treating low-organic excess sludge.
AB  - The sludge production from medium- and small-scale wastewater treatment plants in
      the Three Gorges Reservoir Region is low and non-stable; especially, the organic
      content in this sludge is low (near 40% of VS/TS). An integrated thickening and
      digestion (ISTD) reactor was developed to treat this low-organic excess sludge.
      After a flow test and start-up experiment of the reactor, a running experiment
      was used to investigate the excess sludge treatment efficiency under five
      different excess sludge inflows: 200, 300, 400, 500 and 400 L/d (a mixture of
      excess sludge and primary sludge in a volume ratio of 9:1). This trial was
      carried out in the wastewater treatment plant in Chongqing, which covers 80% of
      the Three Gorges Reservoir Region, under the following conditions: (1) sludge was
      heated to 38-40 degrees C using an electrical heater to maintain anaerobic
      mesophilic digestion; (2) the biogas produced was recirculated to mix raw sludge
      with anaerobic sludge in the reactor under the flow rate of 12.5 L/min. There
      were three main results. Firstly, the flow pattern of the inner reactor was
      almost completely mixed under the air flow of 12.0 L/min using clear water.
      Secondly, under all the different sludge inflows, the water content in the outlet
      sludge was below 93%. Thirdly, the organic content in the outlet sludge was
      decreased from 37% to 30% and from 24% to 20%, whose removal ratio was in
      relation to the organic content of the inlet sludge. The excess sludge treatment
      capacity of the ISTD reactor was according to the organic content in the excess
      sludge.

PMID- 22856316
TI  - Column-mode fluoride removal from aqueous solution by magnesia-loaded fly ash
      cenospheres.
AB  - Column experiments in a fixed bed reactor packed with a certain amount of
      magnesia-loaded fly ash cenospheres (MLC) were conducted to examine the effects
      of adsorbent mass, flow velocities, influent concentrations and coexisting anions
      on fluoride removal. The breakthrough time increased with an increase in
      adsorbent mass, but decreased with increasing influent fluoride concentration.
      The exhaustion time decreased with the increase in the influent fluoride
      concentration. The capacity at the breakthrough point increased with an increase
      in adsorbent mass, flow velocity and the influent fluoride concentration. The
      capacity at the exhaustion point increased with an increase in flow velocity, but
      showed no specific trend with an increase in the initial fluoride concentration.
      The bed volumes at breakthrough point increased with an increase in adsorbent
      mass, flow velocity and the influent fluoride concentration. The empty bed
      contact time decreased with an increase in flow velocity. The coexisting anions
      reduced the adsorption capacity of the fixed bed reactor in the order: mixture of
      all three anions > dihydric phosphate > nitrate > sulfate. The adsorbent
      exhaustion rate decreased with the increase in flow velocity and adsorbent mass,
      whereas it increased with increasing influent fluoride concentration. Columns
      with large amounts of MLC are preferable in order to obtain optimal results
      during the adsorption process, and the higher the flow velocity, the better the
      column performance. The Bohart and Adams model and the Thomas model were applied
      to the experimental results. Column adsorption was reversible and the
      regeneration operation was accomplished by pumping 0.2 M NaOH through the loaded
      MLC column.

PMID- 22856317
TI  - Removal of organic dyes by UV/H2O2 process: modelling and optimization.
AB  - The effects of different operational parameters on the decolorization of a dye
      solution containing C.I. Acid Blue 92 (AB92) or C.I. Acid Black 1 (AB1) by the
      UV/H2O2 process were optimized using response surface methodology (RSM). The
      reaction time, dye and H2O2 initial concentrations and distance of the UV lamp
      from the solution were chosen as input variables. The removal process was
      performed according to a central composite design. Predicted results by the
      proposed models were in good agreement with experimental values (R2 = 0.942 and
      0.957 for AB92 and AB1, respectively). The optimum points were located by
      graphical response surfaces and contour plots. The removal process of the dyes
      was compared and the efficiency difference justified by considering the chemical
      structure of the dyes. Additionally, the electrical energy consumption and the
      related treatment costs were estimated employing the figure-of-merit electrical
      energy per order (E(EO)).

PMID- 22856318
TI  - Characterisation of humic substances formed during co-composting of grass and
      wood wastes with animal grease.
AB  - Meat processing grease wastes were composted with lignocellulosic material.
      Judging by the reduction in the yield of compost lipophilic extract, grease was
      degraded during the first 20 days of composting. Compost humic acids (HA) and
      fulvic acids (FA) were characterized by elemental analysis, Fourier transform
      infrared (FT-IR) spectroscopy and analytical pyrolysis. The compost HA and FA
      fractions contained a ligno-protein complex. The presence of grease (6.7% dry
      weight) during composting had a slight influence on the chemical composition of
      HA and FA. Analytical pyrolysis indicated that, during composting, major changes
      were observed in the FA fraction, namely, the proportion of nitrogen-bearing
      compounds increased and carbohydrate-derived products decreased drastically in
      the final compost. In addition, the shortening of the aliphatic chains of lignin
      derived compounds was observed with an increase in the C6C(0-2)/C6C3 ratio in
      pyrolysates.

PMID- 22856319
TI  - Comparing the effects of three pre-treatment disintegration techniques on aerobic
      sludge digestion: biodegradability enhancement and microbial community monitoring
      by PCR-DGGE.
AB  - The objectives of this work were to compare and investigate the effect of three
      activated sludge disintegration processes before aerobic sludge digestion on 1)
      aerobic biodegradability enhancement and 2) microbial community evolution using
      the polymerase chain reaction-denaturant gel gradient electrophoresis (PCR-DGGE)
      technique. The comparison of three disintegration processes: thermal treatment
      (95 degrees C, 2h), sonication (100,000 kJ/kgTS) and ozonation (0.108 g O3/gTS)
      showed that the disintegration processes acted differently according to the
      composition of the soluble phase and to the DNA damage. Thermal treatment led to
      significant protein solubilization and to DNA modification. Sonication and
      ozonation resulted in similar soluble phase compositions and did not lead to any
      DNA modifications. During activated sludge aerobic digestion, intrinsic
      biodegradability enhancement was observed for thermal and ozone activated sludge
      pre-treatments. The analysis of the DGGE patterns at the end of aerobic digestion
      showed that population diversity was affected by both the aerobic digestion and
      the pre-treatment. The dissimilarity percentages measured at the end of aerobic
      digestion in the control sample and in the treated sludge were equal to 22, 25
      and 20% for thermal treatment, sonication and ozonation respectively. This study
      indicated that PCR-DGGE could be a useful tool for the comparison of
      disintegration processes before and after aerobic digestion.

PMID- 22856320
TI  - Sewage treatment in integrated system of UASB reactor and duckweed pond and reuse
      for aquaculture.
AB  - The performance of a laboratory-scale upflow anaerobic sludge blanket (UASB)
      reactor and a duckweed pond containing Lemna gibba was investigated for
      suitability for treating effluent for use in aquaculture. While treating low
      strength sewage having a chemical oxygen demand (COD) of typically less than 200
      mg/L, with an increase in hydraulic retention time (HRT) from 10.04 to 33.49 h,
      COD removal efficiency of the UASB reactor decreased owing to a decrease in
      organic loading rate (OLR) causing poor mixing in the reactor. However, even at
      the lower OLR (0.475 kg COD/(m3 x d)), the UASB reactor gave a removal efficiency
      of 68% for COD and 74% for biochemical oxygen demand (BOD). The maximum COD, BOD,
      ammonia-nitrogen and phosphate removal efficiencies of the duckweed pond were
      40.77%, 38.01%, 61.87% and 88.57%, respectively. Decreasing the OLR by increasing
      the HRT resulted in an increase in efficiency of the duckweed pond for removal of
      ammonia-nitrogen and phosphate. The OLR of 0.005 kg COD/(m2 x d) and HRT of 108 h
      in the duckweed pond satisfied aquaculture quality requirements. A specific
      growth rate of 0.23% was observed for tilapia fish fed with duckweed harvested
      from the duckweed pond. The economic analysis proved that it was beneficial to
      use the integrated system of a UASB reactor and a duckweed pond for treatment of
      sewage.

PMID- 22856321
TI  - Heavy metal removal by combining anaerobic upflow packed bed reactors with water
      hyacinth ponds.
AB  - The removal of four selected heavy metals (Cu, Cd, Pb and Zn) has been assessed
      in an upflow anaerobic packed bed reactor filled with porous volcanic rock as an
      adsorbent and an attachment surface for bacterial growth. Two different feeding
      regimes were applied using low (5 mg L(-1) of heavy metal each) and high (10 mg
      L(-1) of heavy metal each) strength wastewater. After a start-up and
      acclimatization period of 44 days, each regime was operated for a period of 10
      days with a hydraulic retention time of one day. Good removal efficiencies of at
      least 86% were achieved for both the low and high strength wastewater. A
      subsequent water hyacinth pond with a hydraulic retention time of one day removed
      an additional 61% Cd, 59% Cu, 49% Pb and 42% Zn, showing its importance as a
      polishing step. The water hyacinth plant in the post-treatment step accumulated
      heavy metals mainly in the root system. Overall metal removal efficiencies at the
      outlet of the integrated system were 98% for Cd, 99% for Cu, 98% for Pb and 84%
      for Zn. Therefore, the integrated system can be used as an alternative treatment
      system for metal-polluted wastewater, especially in developing countries.

PMID- 22856322
TI  - Transient fibril structures facilitating nonenzymatic self-replication.
AB  - An emerging new direction of research focuses on developing "self-synthesizing
      materials", those supramolecular structures that can promote their own formation
      by accelerating the synthesis of building blocks and/or an entire assembly. It
      was postulated recently that practical design of such systems can benefit from
      the ability to control the assembly of amphiphilic molecules into nanostructures.
      We describe here the self-assembly pathway of short amphiphilic peptides into
      various forms of soluble beta-sheet structures--beta-plates, fibrils, and hollow
      nanotubes--and their consequent activity as autocatalysts for the synthesis of
      monomeric peptides from simpler building blocks. A detailed kinetic analysis of
      both the self-assembly and self-replication processes allows us to suggest a full
      model and simulate the replication process, revealing that only specific
      structures, primarily fibrils that are stable within the solution for a time
      shorter than a few hours, can be active as catalysts. Interestingly, we have
      found that such a process also induces fibril reproduction, in a mechanism very
      similar to the propagation of prion proteins by transmission of misfolded states.

PMID- 22856323
TI  - Self-assembled bilayers on indium-tin oxide (SAB-ITO) electrodes: a design for
      chromophore-catalyst photoanodes.
AB  - A novel approach for creating assemblies on metal oxide surfaces via the addition
      of a catalyst overlayer on a chomophore monolayer derivatized surface is
      described. It is based on the sequential self-assembly of a chromophore,
      [Ru(bpy)(4,4'-(PO(3)H(2)bpy)(2))](2+), and oxidation catalyst,
      [Ru(bpy)(P(2)Mebim(2)py)OH(2)](2+), pair, resulting in a spatially separated
      chromophore-catalyst assembly.

PMID- 22856324
TI  - Annona montana fruit and leaves improve the glycemic and lipid profiles of Wistar
      rats.
AB  - Species of the family Annonaceae has been used traditionally as a medicinal plant
      in tropical regions of South and North America and in Africa. Annona montana is
      known popularly as false graviola and originates from tropical America and can be
      cultivated throughout Brazil. There are no studies in the literature that
      associate A. montana with the metabolic profile of animals. Therefore, the
      purpose of this work was to assess the effects of the consumption of pulp and
      leaves of this plant on the metabolic profile of Wistar rats. The animals, which
      were treated for 40 days, were divided into two control groups--treated with
      water via gavage and ad libitum, respectively, and two treated groups--one
      treated with leaf juice and the other with pulp juice of the fruit. Glycemia,
      lipids, and body weight were found to decrease and high density lipoprotein
      cholesterol (HDL-c) levels to increase in the animals treated with leaf juice.
      The group treated with pulp juice showed a reduction in lipids and augmented HDL
      c. The use of A. montana may have beneficial effects in the prevention of
      diabetes mellitus and dyslipidemia and may thus contribute to the prevention of
      cardiovascular diseases.

PMID- 22856325
TI  - Decision-making in healthcare: a practical application of partial least square
      path modelling to coverage of newborn screening programmes.
AB  - BACKGROUND: Decision-making in healthcare is complex. Research on coverage
      decision-making has focused on comparative studies for several countries,
      statistical analyses for single decision-makers, the decision outcome and
      appraisal criteria. Accounting for decision processes extends the complexity, as
      they are multidimensional and process elements need to be regarded as latent
      constructs (composites) that are not observed directly. The objective of this
      study was to present a practical application of partial least square path
      modelling (PLS-PM) to evaluate how it offers a method for empirical analysis of
      decision-making in healthcare. METHODS: Empirical approaches that applied PLS-PM
      to decision-making in healthcare were identified through a systematic literature
      search. PLS-PM was used as an estimation technique for a structural equation
      model that specified hypotheses between the components of decision processes and
      the reasonableness of decision-making in terms of medical, economic and other
      ethical criteria. The model was estimated for a sample of 55 coverage decisions
      on the extension of newborn screening programmes in Europe. Results were
      evaluated by standard reliability and validity measures for PLS-PM. RESULTS:
      After modification by dropping two indicators that showed poor measures in the
      measurement models' quality assessment and were not meaningful for newborn
      screening, the structural equation model estimation produced plausible results.
      The presence of three influences was supported: the links between both
      stakeholder participation or transparency and the reasonableness of decision
      making; and the effect of transparency on the degree of scientific rigour of
      assessment. Reliable and valid measurement models were obtained to describe the
      composites of 'transparency', 'participation', 'scientific rigour' and
      'reasonableness'. CONCLUSIONS: The structural equation model was among the first
      applications of PLS-PM to coverage decision-making. It allowed testing of
      hypotheses in situations where there are links between several non-observable
      constructs. PLS-PM was compatible in accounting for the complexity of coverage
      decisions to obtain a more realistic perspective for empirical analysis. The
      model specification can be used for hypothesis testing by using larger sample
      sizes and for data in the full domain of health technologies.

PMID- 22856328
TI  - Oxidative stress in ulcerative colitis: an old concept but a new concern.
AB  - Ulcerative colitis is an idiopathic, chronic and relapsing inflammatory bowel
      disease, which elicits the risk of colorectal cancer, the third most common
      malignancy in humans. It has been known for a long time that oxidative stress is
      a major pathogenic factor in the inflamed tissue that can pave the way towards
      DNA damage and carcinogenesis. However, the DNA damage produced due to oxidative
      stress in the inflamed tissue is not limited to the local site but extends
      globally, thereby augmenting the risk of global carcinogenesis. Targeting
      oxidative stress may provide an exciting avenue to combat inflammation-associated
      local as well as global DNA damage and the subsequent carcinogenesis. The present
      review portrays the role of oxidative stress in the pathogenesis of ulcerative
      colitis and the associated local as well as global DNA damage, which may lead to
      carcinogenesis.

PMID- 22856327
TI  - Genetics of gene expression responses to temperature stress in a sea urchin gene
      network.
AB  - Stress responses play an important role in shaping species distributions and
      robustness to climate change. We investigated how stress responses alter the
      contribution of additive genetic variation to gene expression during development
      of the purple sea urchin, Strongylocentrotus purpuratus, under increased
      temperatures that model realistic climate change scenarios. We first measured
      gene expression responses in the embryos by RNA-seq to characterize molecular
      signatures of mild, chronic temperature stress in an unbiased manner. We found
      that an increase from 12 to 18  degrees C caused widespread alterations in gene
      expression including in genes involved in protein folding, RNA processing and
      development. To understand the quantitative genetic architecture of this
      response, we then focused on a well-characterized gene network involved in
      endomesoderm and ectoderm specification. Using a breeding design with wild-caught
      individuals, we measured genetic and gene-environment interaction effects on 72
      genes within this network. We found genetic or maternal effects in 33 of these
      genes and that the genetic effects were correlated in the network. Fourteen
      network genes also responded to higher temperatures, but we found no significant
      genotype-environment interactions in any of the genes. This absence may be owing
      to an effective buffering of the temperature perturbations within the network. In
      support of this hypothesis, perturbations to regulatory genes did not affect the
      expression of the genes that they regulate. Together, these results provide novel
      insights into the relationship between environmental change and developmental
      evolution and suggest that climate change may not expose large amounts of cryptic
      genetic variation to selection in this species.

PMID- 22856329
TI  - Insect ryanodine receptor: distinct but coupled insecticide binding sites for [N
      C(3)H(3)]chlorantraniliprole, flubendiamide, and [(3)H]ryanodine.
AB  - Radiolabeled anthranilic diamide insecticide [N-C(3)H(3)]chlorantraniliprole was
      synthesized at high specific activity. It was compared with phthalic diamide
      insecticide flubendiamide and [(3)H]ryanodine in radioligand binding studies with
      house fly muscle membranes to provide the first direct evidence with a native
      insect ryanodine receptor that the major anthranilic and phthalic diamide
      insecticides bind at different allosterically coupled sites, i.e., there are
      three distinct Ca(2+)-release channel targets for insecticide action.

PMID- 22856330
TI  - Changes in spinal excitability during dual task performance.
AB  - The authors investigated how the nervous system responds to dual task
      performance. Because dual tasking is associated with greater postural challenges,
      it was hypothesized that spinal excitability would be reduced when simultaneously
      performing 2 tasks. For this experiment, participants maintained a lying or
      standing posture with or without performing a concurrent cognitive task (i.e.,
      reacting to an auditory tone). Spinal excitability was assessed by eliciting the
      soleus Hoffmann reflex (H-reflex). Results indicated that the H-reflex was 6.4 +/
      2.3% smaller (p = .011) when dual compared to single tasking. The reduced H
      reflex amplitude, indicating a depressed spinal excitability, when dual tasking
      is suggested to reflect a neural strategy that individuals adopt to maintain
      postural stability when cognitive resources are divided between 2 concurrent
      tasks.

PMID- 22856331
TI  - One-pot, two-step conversion of aldehydes to phosphonyl- and sulfonylpyrazoles
      using Bestmann-Ohira reagent.
AB  - A one-pot, two-step, three-component method for the conversion of commercially
      available aldehydes to phosphonylpyrazoles has been developed, demonstrating, for
      the first time, the dual reactivity of the Bestmann-Ohira reagent (BOR) in a
      single-pot transformation. This method, extended to the synthesis of
      sulfonylpyrazoles by employing BOR in the first step and a diazomethyl sulfone in
      the second step, is complementary, with regard to regioselectivity, to the
      previous methods for the synthesis of such functionalized pyrazoles.

PMID- 22856332
TI  - Multiple informant agreement on the anxiety disorders interview schedule in youth
      with autism spectrum disorders.
AB  - OBJECTIVE: The purpose of this study was to examine child, parent, and
      clinician's consensus agreement on the Anxiety Disorders Interview Schedule,
      Child and Parent versions (ADIS-C/P) in a sample of children and adolescents with
      autism spectrum disorders (ASD). METHOD: Youth with ASD (n=85; age range=7-17
      years) and their parents were each administered the ADIS-C/P by a trained
      clinician. Consensus diagnoses were determined in a clinical conference using
      best estimate procedures that incorporated all available information. RESULTS:
      Children and youth with ASD diagnoses generally showed poor diagnostic agreement
      with parents and clinical consensus, whereas parents showed good-to-excellent
      diagnostic agreement with clinical consensus diagnoses. Diagnostic agreement
      between parents and consensus was moderated by the specific ASD diagnosis.
      Otherwise, the pattern of relationships did not systematically differ as a
      function of age or externalizing comorbidity. CONCLUSIONS: These data suggest
      that parent and youth agreement regarding the presence of clinical levels of
      anxiety is markedly poor among youth with ASD. Additionally, clinicians are
      likely to base their diagnostic impressions on parent report, placing minimal
      emphasis on child report.

PMID- 22856333
TI  - Jasmonic acid is involved in the signaling pathway for fungal endophyte-induced
      volatile oil accumulation of Atractylodes lancea plantlets.
AB  - BACKGROUND: Jasmonic acid (JA) is a well-characterized signaling molecule in
      plant defense responses. However, its relationships with other signal molecules
      in secondary metabolite production induced by endophytic fungus are largely
      unknown. Atractylodes lancea (Asteraceae) is a traditional Chinese medicinal
      plant that produces antimicrobial volatiles oils. We incubated plantlets of A.
      lancea with the fungus Gilmaniella sp. AL12. to research how JA interacted with
      other signal molecules in volatile oil production. RESULTS: Fungal inoculation
      increased JA generation and volatile oil accumulation. To investigate whether JA
      is required for volatile oil production, plantlets were treated with JA
      inhibitors ibuprofen (IBU) and nordihydroguaiaretic acid. The inhibitors
      suppressed both JA and volatile oil production, but fungal inoculation could
      still induce volatile oils. Plantlets were further treated with the nitric oxide
      (NO)-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl
      3-oxide potassium salt (cPTIO), the H2O2 inhibitors diphenylene iodonium (DPI)
      and catalase (CAT), and the salicylic acid (SA) biosynthesis inhibitors
      paclobutrazol and 2-aminoindan-2-phosphonic acid. With fungal inoculation, IBU
      did not inhibit NO production, and JA generation was significantly suppressed by
      cPTIO, showing that JA may act as a downstream signal of the NO pathway.
      Exogenous H2O2 could reverse the inhibitory effects of cPTIO on JA generation,
      indicating that NO mediates JA induction by the fungus through H2O2-dependent
      pathways. With fungal inoculation, the H2O2 scavenger DPI/CAT could inhibit JA
      generation, but IBU could not inhibit H2O2 production, implying that H2O2
      directly mediated JA generation. Finally, JA generation was enhanced when SA
      production was suppressed, and vice versa. CONCLUSIONS: Jasmonic acid acts as a
      downstream signaling molecule in NO- and H2O2-mediated volatile oil accumulation
      induced by endophytic fungus and has a complementary interaction with the SA
      signaling pathway.

PMID- 22856334
TI  - LuxS-dependent AI-2 regulates versatile functions in Enterococcus faecalis V583.
AB  - Bacteria utilize a quorum sensing (QS) system to coordinate gene expression by
      monitoring the concentration of molecules known as autoinducers (AI). In the
      present study, we confirmed the presence of a LuxS/AI-2 dependent QS system in
      vancomycin-resistant Enterococcus faecalis V583. Then, the cellular targets
      controlled by AI-2 were identified by comparative proteomics analysis in order to
      elucidate the possible role of AI-2 in E. faecalis. Results demonstrated 15
      proteins that are differentially expressed upon the addition of AI-2, including
      proteins involved in metabolism, translation, energy production and/or
      conversion, and cell wall biogenesis. Glyceraldehyde-3-phosphate dehydrogenase
      and malate dehydrogenase associated with carbohydrate metabolism and energy
      production were up-regulated upon inducing by AI-2. In addition, externally added
      AI-2 could down-regulate acetyl-coenzyme A carboxylase and ornithine
      carbamoyltransferase, two key enzyme involved in metabolism. All these data
      suggest that AI-2 signaling may play a role in the regulation of a number of
      important metabolic properties of E. faecali. We further investigated the role of
      AI-2 in biofilm formation by E. faecalis, showing the addition of AI-2 to E.
      faecalis V583 cultures resulted in increased biofilm formation. Our results
      provide important clues to the role of a LuxS/AI-2 dependent QS system in
      vancomycin-resistant E. faecalis.

PMID- 22856335
TI  - Infrared optical constants of crystalline sodium chloride dihydrate: application
      to study the crystallization of aqueous sodium chloride solution droplets at low
      temperatures.
AB  - Complex refractive indices of sodium chloride dihydrate, NaCl.2H(2)O, have been
      retrieved in the 6000-800 cm(-1) wavenumber regime from the infrared extinction
      spectra of crystallized aqueous NaCl solution droplets. The data set is valid in
      the temperature range from 235 to 216 K and was inferred from crystallization
      experiments with airborne particles performed in the large coolable aerosol and
      cloud chamber AIDA at the Karlsruhe Institute of Technology. The retrieval
      concept was based on the Kramers-Kronig relationship for a complex function of
      the optical constants n and k whose imaginary part is proportional to the optical
      depth of a small particle absorption spectrum in the Rayleigh approximation. The
      appropriate proportionality factor was inferred from a fitting algorithm applied
      to the extinction spectra of about 1 MUm sized particles, which, apart from
      absorption, also featured a pronounced scattering contribution. NaCl.2H(2)O is
      the thermodynamically stable crystalline solid in the sodium chloride-water
      system below the peritectic at 273.3 K; above 273.3 K, the anhydrous NaCl is more
      stable. In contrast to anhydrous NaCl crystals, the dihydrate particles reveal
      prominent absorption signatures at mid-infrared wavelengths due to the hydration
      water molecules. Formation of NaCl.2H(2)O was only detected at temperatures
      clearly below the peritectic and was first evidenced in a crystallization
      experiment conducted at 235 K. We have employed the retrieved refractive indices
      of NaCl.2H(2)O to quantify the temperature dependent partitioning between
      anhydrous and dihydrate NaCl particles upon crystallization of aqueous NaCl
      solution droplets. It was found that the temperature range from 235 to 216 K
      represents the transition regime where the composition of the crystallized
      particle ensemble changes from almost only NaCl to almost only NaCl.2H(2)O
      particles. Compared to the findings on the NaCl/NaCl.2H(2)O partitioning from a
      recent study conducted with micron-sized NaCl particles deposited onto a surface,
      the transition regime from NaCl to NaCl.2H(2)O is shifted by about 13 K to lower
      temperatures in our study. This is obviously related to the different
      experimental conditions of the two studies. The partitioning between the two
      solid phases of NaCl is essential for predicting the deliquescence and ice
      nucleation behavior of a crystalline aerosol population which is subjected to an
      increasing relative humidity.

PMID- 22856336
TI  - Comparative diagnostic efficacy of serum squamous cell carcinoma antigen in
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common liver malignancy in
      Nigeria. Hepatitis B and C viruses, alcohol and Aflatoxin B are among the various
      aetiologies. More work needs to be done in the search for markers that will aid
      early detection of this condition as it is uniformly fatal once advanced.
      Alphafetoprotein (AFP) remains the most widely used tumour marker of HCC
      detection in spite of its known shortcomings. The objective of this study was to
      determine the efficacy of serum squamous cell carcinoma antigen (SCCA) , in
      comparison to alphafetoprotein in the detection of HCC. METHOD: Sixty patients
      with HCC and thirty apparently healthy controls attending the Medical Outpatient
      Department(MOPD) of the University College Hospital Ibadan(UCH) Nigeria were
      selected for the study. Questionnaire was used to collect clinical data while
      AFP, SCCA levels, serum HBsAg and anti-HCV were determined using ELISA method-
      (Diagnostic Automation Inc. Canada). Abdominal ultrasound scan was also done.
      RESULT: Thirty one (51.7%) out of 60 selected cases were positive for HBsAg while
      six (20%) out of 30 controls were positive for HBsAg(p = 0.004). Out of the 60
      cases selected for this study, only 2 (3.3.%) cases were positive for hepatitis C
      virus, while only 1(3.3%) out of 30 control was positive for hepatitis C virus(p
      = 0.74).The mean AFP value for cases with HCC was 393.21 ng/ml +/-386.97 compared
      to the control group which was 5.60 +/- 13.03 ng/ml (p value 0.001). The mean
      SCCA level was 0.64 +/- 0.56 ng/ml and 0.71 +/- 0.65 ng/ml for cases and controls
      respectively (p = 0.631). CONCLUSION: Alphafetoprotein remains a good tumour
      marker for the diagnosis of HCC. Serum squamous cell carcinoma antigen(SCCA) has
      no discriminatory power and may not be useful as a tumour marker for Nigerians
      with hepatocellular carcinoma.

PMID- 22856337
TI  - Multifocal VEP and OCT findings in patients with primary open angle glaucoma: a
      cross-sectional study.
AB  - BACKGROUND: To evaluate objectively the anatomical and functional changes of
      optic nerve in eyes with primary open angle glaucoma (POAG) by the joint use of
      optical coherence tomography (OCT) and multifocal visual evoked potentials
      (mfVEP). METHODS: 29 eyes with open angle glaucoma and visual field defects, as
      well as 20 eyes of 10 age-matched control normal subjects were tested. All
      participants underwent a complete ophthalmological examination. Moreover,
      Humphrey visual field test, OCT examination and recording of mfVEP were
      performed. Amplitude and implicit time of mfVEP, as well as RNFL thickness were
      measured. Differences in density components of mfVEP and in RNFL thickness among
      POAG eyes and control eyes were examined using Student's t-test. RESULTS: In
      glaucomatous eyes the mean Retinal Response Density (RRD) was lower than normal
      in ring 1, 2 and 3 of mfVEP (p < 0.0001). Specifically the mean amplitude of
      mfVEP in POAG eyes was estimated at 34.2 +/- 17.6 nV/deg2, 6.9 +/- 4.8 nV/deg2
      and 2.6 +/- 1.6 nV/deg2 in rings 1, 2 and 3 respectively. In contrast the mean
      implicit time was similar to control eyes. In addition, the mean RNFL thickness
      in POAG eyes was estimated at 76.8 +/- 26.6 MUm in the superior area, 52.1 +/-
      16.3 MUm in the temporal area, 75.9 +/- 32.5 MUm in the inferior area and 58.6 +/
      19.4 MUm in the nasal area. There was a statistically significant difference in
      RNFL thickness in all peripapillary areas (p < 0.0001) between POAG eyes and
      controls, with superior and inferior area to present the highest decrease.
      CONCLUSIONS: Our study shows that, although Standard Automatic Perimetry is the
      gold standard to evaluate glaucomatous neuropathy, the joint use of mfVEP and OCT
      could be useful in better monitoring glaucoma progression.

PMID- 22856338
TI  - Cardiovascular and perceptual responses to blood-flow-restricted resistance
      exercise with differing restrictive cuffs.
AB  - The purpose of this study was to determine (i) the cardiovascular responses to
      acute blood-flow-restricted (BFR) resistance exercise and (ii) the influence of
      applied BFR cuff type on the cardiovascular and perceptual responses. METHODS: In
      a randomized, crossover design, 27 participants wore either a 5.0 cm wide elastic
      cuff or a 13.5 cm wide non-elastic cuff around the thigh while performing four
      sets of knee extension exercise using 20% of 1-RM. Brachial and central blood
      pressure (BP) and aortic augmentation index (AIx) were measured before and after
      the restrictive cuffs were applied and inflated, after the 2nd and 4th set of
      resistance exercise, and 5 and 15 min following the 4th set of exercise. Ratings
      of perceived exertion and pain were obtained before exercise and after the 2nd
      and 4th set of exercise. RESULTS: Both brachial and central BPs increased and AIx
      decreased during BFR exercise but returned to baseline levels within 15 min
      following exercise. The wide cuffs caused a greater elevation in heart rate,
      brachial and central BPs, perceived effort and pain and a greater decrease in AIx
      during the BFR exercise. CONCLUSIONS: These findings suggest that low-intensity
      BFR resistance exercise does not appear to acutely negatively affect the
      vasculature. Also, cuff type will greatly affect cardiovascular and perceptual
      responses to BFR resistance exercise and thus is an important consideration in
      study design.

PMID- 22856339
TI  - Blood flow velocity and vascular resistance during passive leg exercise in the
      critically ill patient.
AB  - Passive range of motion exercise is a very common physical therapy treatment for
      patients admitted to an intensive care unit. However is the knowledge scarce
      regarding its impact on blood circulation in the extremities. The objective of
      this study was therefore to investigate the effect of passive range of motion on
      arterial peripheral leg blood flow velocity (BFV) and vascular resistance. A
      cross-sectional consecutive study of twelve patients admitted to an intensive
      care unit and twelve healthy age- and gender-matched controls was conducted.
      Passive range of motion was performed in one leg by a physical therapist. Blood
      flow velocities and resistance index in the common femoral artery (CFA), blood
      pressure and heart rate were measured before, directly after and at rest after
      passive range of motion. No changes were seen in BFV or resistance index in the
      patient group or the control group. No changes were found in blood pressure or
      heart rate in the patient group. In the control group, changes were found in
      systolic and mean blood pressure, with a higher pressure before passive range of
      motion. The controls had lower BFV and higher resistance index than the patients
      when comparing the groups. The conclusion of this study including twelve patients
      is that passive range of motion does not alter BFV or resistance index in the CFA
      in comatose and/or sedated critically ill patients.

PMID- 22856340
TI  - Signal-morphology impedance cardiography during incremental cardiopulmonary
      exercise testing in pulmonary arterial hypertension.
AB  - BACKGROUND: Haemodynamic responses to exercise are related to physical impairment
      and worse prognosis in patients with pulmonary arterial hypertension (PAH). It is
      clinically relevant, therefore, to investigate the practical usefulness of non
      invasive methods of monitoring exercise haemodynamics in this patient population.
      METHODS: Using a novel impedance cardiography (ICG) approach that does not
      require basal impedance estimations and relies on a morphological analysis of the
      impedance signal (Signal-Morphology-ICG(TM)), stroke volume (SV) and cardiac
      index (CI) were evaluated in 50 patients and 21 age-matched controls during a
      ramp-incremental cardiopulmonary exercise testing. RESULTS: Technically
      unacceptable readings were found in 12 of 50 (24%) patients. In the remaining
      subjects, early decrease (N = 9) or a 'plateau' in SV (N = 8) and Delta (peak
      unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). DeltaCI
      <= 1.5-fold and early estimated lactate threshold were the only independent
      predictors of a severely reduced peak oxygen uptake (VO(2)) in patients (R(2) =
      0.71, P<0.001). The finding of DeltaCI <= 1.5-fold plus peak VO(2) < 50%
      predicted was associated with a number of clinical and functional markers of
      disease severity (P<0.001). In addition, abnormal SV responses and DeltaCI <= 1.5
      fold were significantly related to 1-year frequency of PAH-related adverse events
      (death and balloon atrial septostomy, N = 8; P<0.05). CONCLUSIONS: 'Qualitative'
      and 'semi-quantitative' signal-morphology impedance cardiography(TM)
      (PhysioFlow(TM)) during incremental exercise provided clinically useful
      information to estimate disease severity and short-term prognosis in patients
      with PAH in whom acceptable impedance signals could be obtained.

PMID- 22856341
TI  - Aortic reservoir function, estimated myocardial demand and coronary perfusion
      pressure following steady-state and interval exercise.
AB  - Aortic reservoir function is a measure of the aorta's ability to distribute blood
      during diastole, attenuating the pulsatility of blood flow, and is important in
      balancing cardiac flow. Effects of acute high versus moderate exercise intensity
      on reservoir function and cardiac energetics is unknown. Eighteen athletes
      completed a interval (INT) and steady-state (SS) cycling bout at 60% of VO(2) 
      peak. Reservoir function was calculated as the ratio of diastolic run-off to
      stroke volume and expressed as a percentage. Coronary perfusion pressure was
      derived from tissue Doppler imaging and echocardiography. Systolic tension-time
      integral (TTI) from the aortic pressure waveform served as a measure of
      myocardial oxygen consumption. All measures were made at rest, 30-min
      postexercise and 60-min postexercise. Average reservoir function before SS was
      76%, which was reduced to 62% 30-min post-SS and 67% 60-min post-SS (P<0.05).
      Significantly greater reductions in reservoir function were seen following INT
      (from 71% pre-INT to 45% 30-min post-INT and 53% 60-min INT, P<0.05). Estimated
      coronary perfusion pressure was reduced 30 min following INT but not SS; both
      bouts reduced coronary perfusion pressure at 60-min postexercise (P<0.05). TTI
      increased following both INT and SS at 30- and 60-min postexercise with greater
      increases following INT (P<0.05). Following exercise, reservoir function was
      associated with TTI (P<0.05), but not coronary perfusion pressure (P>0.05). We
      conclude that reservoir function is attenuated following acute SS and INT, but
      these reductions were greater post-INT, suggesting that exercise intensity
      affects reservoir function. Reduction of reservoir function following exercise is
      related to TTI, a reflection of myocardial oxygen consumption but apparently not
      associated with coronary perfusion pressure.

PMID- 22856342
TI  - Differential vasodilatory responses to local heating in facial, glabrous and
      hairy skin.
AB  - BACKGROUND AND AIMS: Local heating induces biphasic cutaneous vasodilation in non
      glabrous skin of the forearm. However, little data exist in other skin regions,
      despite the prevalence of facial flushing disorders. We hypothesized that facial
      skin will have greater initial peak responses to local heating than forearm skin
      because of neural differences between sites and, furthermore, axon reflex
      vasodilation will be eliminated in facial sites with sensory blockade. METHODS:
      Skin blood flow (laser-Doppler flowmetry) responses of healthy, non-obese
      subjects to local heating (32-42 degrees C in ~5 min, held 40 min) in the
      forehead (n = 22), cheek (n = 22), forearm (n = 22) and palm (n = 13) were
      expressed as percentage of maximum cutaneous vascular conductance (CVC; flux/mean
      arterial pressure). In an additional group (n = 7), sensation was blocked
      (topical prilocaine-lidocaine) prior to the local heating protocol. RESULTS:
      Prior to heating, CVC differences were noted (forearm = 10 +/- 3, cheek = 19 +/-
      3, forehead = 16 +/- 1 and palm = 65 +/- 11%CVC; P<0.05). Initial peak CVC was
      similar between forehead, cheek and forearm (85 +/- 3, 92 +/- 2, and 91 +/-
      6%CVC, respectively), but elevated in the palm (120 +/- 8%CVC; P<0.05). Compared
      to facial control sites, sensory blockade delayed increases in both cheek and
      forehead (P<0.05) CVC but did not change magnitude of the biphasic response
      (P>0.05). CONCLUSIONS: These data indicate that facial skin initial CVC peaks to
      local heating are similar to non-glabrous skin. In contrast to forearm responses,
      facial topical sensory blockade does not abate axon reflex responses to local
      heating. Palm skin data indicate that maximal skin blood flow is not obtained
      during local heating as it is in non-glabrous skin.

PMID- 22856343
TI  - Increased intrathoracic pressure affects cerebral oxygenation following cardiac
      surgery.
AB  - BACKGROUND: Cerebral oximetry reflects circulatory stability during surgery. We
      evaluated whether frontal lobe oxygenation is influenced by a transient increase
      in intrathoracic pressure as induced by a lung recruitment manoeuvre. METHODS:
      Intrathoracic pressure was increased to 40 cm H(2)O for 20 s immediately after
      cardiac surgery in ten patients (age 64 +/- 10 year, mean +/- SD) with frontal
      lobe oxygenation assessed by near-infrared spectroscopy and cardiac output by
      thermodilution. RESULTS: The lung recruitment manoeuvre increased arterial O(2)
      pressure (from 29 +/- 15 to 40 +/- 12 kPa) with a decrease in mean arterial
      pressure (MAP) (from 69 +/- 7 to 55 +/- 11 mmHg), cardiac output (from 5.4 +/-
      0.6 to 5.0 +/- 0.7 l min(-1)) and frontal lobe oxygenation (from 68 +/- 9 to 60
      +/- 13%; all P<0.05). A reduction in MAP by more than 15 mmHg caused cerebral
      desaturation by 10%, the lowest cerebral oxygenation (44%) was with a reduction
      in MAP by 24 mmHg, and according to multiple linear regression, only MAP
      predicted cerebral deoxygenation (P = 0.03). Following the lung recruitment
      manoeuvre, hemodynamic variables and frontal lobe oxygenation were restored.
      CONCLUSIONS: A lung recruitment manoeuvre decreases frontal lobe oxygenation when
      MAP is low suggesting that with increased intrathoracic pressure, arterial
      pressure should be kept within the limits of cerebral autoregulation.

PMID- 22856344
TI  - Regional LV deformation in healthy individuals during isovolumetric contraction
      and ejection phases assessed by 2D speckle tracking echocardiography.
AB  - PURPOSE: The main purpose of the this human study was by speckle tracking imaging
      to characterize the regional and temporal distribution of normal left ventricular
      (LV) deformation and the LV geometry during isovolumetric contraction (IVC) and
      the ejection phase. METHODS: Twelve healthy young men [22 (2.3) years] were
      included. Longitudinal and circumferential strain and local twist angle were
      measured at four LV short-axis levels: basal, papillary, subpapillary and apical
      level during IVC and ejection phases. In addition, LV length from apex to the
      atrio-ventricular level, two diameters at LV basal short-axis level and atrio
      ventricular plane displacement (AVPD) were measured to characterize LV shape
      during IVC. RESULTS: During IVC, longitudinal and circumferential shortening was
      demonstrated at all four short-axis levels from base to apex, while the LV made a
      basal counterclockwise and apical clockwise rotation representing untwist. In
      addition, there was a reduction in LV length and changes in short-axis diameters
      at basal level and AVPD from end-diastole to end-IVC, reflecting that the LV
      changed from an oval to a more spherical shape. At end-systole, longitudinal and
      circumferential shortening and local twist angle were significantly increased
      towards apex (P<0.05). CONCLUSION: This study demonstrated that the IVC in
      healthy humans is characterized by regional longitudinal and circumferential
      shortening and LV untwist, which occurs parallel to geometric changes of the LV
      into a spherical shape. During ejection, increased regional gradients of LV
      deformation towards apex in LV longitudinal and circumferential shortening and
      local and net twist angle were demonstrated.

PMID- 22856345
TI  - Muscle force recovery in relation to muscle oxygenation.
AB  - The aim of this study was to investigate the relative contribution of human
      muscle reoxygenation on force recovery following a maximal voluntary contraction
      (MVC). Ten athletes (22.9 +/- 4.0 years) executed a plantar-flexion sequence
      including two repeated MVCs [i.e. a 30-s MVC (MVC(30)) followed by a 10-s MVC
      (MVC(10))] separated by 10, 30, 60, 120 or 300 s of passive recovery. A 10-min
      passive recovery period was allowed between each MVC sequence. This procedure was
      randomly repeated with two different recovery conditions: without (CON) or with
      (OCC) arterial occlusion of the medial gastrocnemius. During OCC, the occlusion
      was maintained from the end of MVC(30) to the end of MVC(10). Muscle oxygenation
      (Near-infrared spectroscopy, NIRS, [Hb(diff) ]) was continuously measured during
      all MVC sequences and expressed as a percentage of the maximal changes in optical
      density observed during MVC(30). Maximal Torque was analysed at the start of each
      contraction. Torque during each MVC(10) was expressed as a percentage of the
      Torque during the previous MVC(30). Torque recovery was complete within 300 s
      after MVC(30) during CON (MVC(10) = 101.8 +/- 5.0%); 88.6 +/- 8.9% of the Torque
      was recovered during OCC (P = 0.005). There was also a moderate correlation
      between absolute level of muscle oxygenation and Torque (r = 0.32 (90% CI,
      0.09;0.52), P = 0.02). Present findings confirm the role of human muscle
      oxygenation in muscular force recovery during repeated-maximal efforts. However,
      the correlation between absolute muscle oxygenation and force level during
      recovery is only moderate, suggesting that other mechanisms are likely involved
      in the force recovery process.

PMID- 22856346
TI  - Relationship between peak cardiac pumping capability and indices of cardio
      respiratory fitness in healthy individuals.
AB  - Cardiac power output (CPO) is a unique and direct measure of overall cardiac
      function (i.e. cardiac pumping capability) that integrates both flow- and
      pressure-generating capacities of the heart. The present study assessed the
      relationship between peak exercise CPO and selected indices of cardio-respiratory
      fitness. Thirty-seven healthy adults (23 men and 14 women) performed an
      incremental exercise test to volitional fatigue using the Bruce protocol with gas
      exchange and ventilatory measurements. Following a 40-min recovery, the subjects
      performed a constant maximum workload exercise test at or above 95% of maximal
      oxygen consumption. Cardiac output was measured using the exponential CO(2) 
      rebreathing method. The CPO, expressed in W, was calculated as the product of the
      mean arterial blood pressure and cardiac output. At peak exercise, CPO was well
      correlated with cardiac output (r = 0.92, P<0.01), stroke volume (r = 0.90,
      P<0.01) and peak oxygen consumption (r = 0.77, P<0.01). The coefficient of
      correlation was moderate between CPO and anaerobic threshold (r = 0.47, P<0.01),
      oxygen pulse (r = 0.57, P<0.01), minute ventilation (r = 0.53, P<0.01) and carbon
      dioxide production (r = 0.56, P<0.01). Small but significant relationship was
      found between peak CPO and peak heart rate (r = 0.23, P<0.05). These findings
      suggest that only peak cardiac output and stroke volume truly reflect CPO. Other
      indices of cardio-respiratory fitness such as oxygen consumption, anaerobic
      threshold, oxygen pulse, minute ventilation, carbon dioxide production and heart
      rate should not be used as surrogates for overall cardiac function and pumping
      capability of the heart.

PMID- 22856347
TI  - The effects of exercise modality on the incidence of plateau at VO2max.
AB  - The purpose of this study was to determine the effect of exercise modality on the
      incidence of plateau at VO2max. Twelve recreationally active men (age, 21.7 +/-
      2.3 year; mass, 74.8 +/- 6.5 kg; height, 177.6 +/- 5.6 cm) completed four
      incremental tests to volitional exhaustion, of which two were completed on a
      treadmill (TRE) and two were completed using a cycle ergometer (CYC). The work
      rate employed for CYC was 1 W.2 s(-1) from an initial loading of 100 W with
      cadence being maintained at 60 rpm. For TRE, the workload (gradient) increased at
      a rate of 0.5% . 30 s(-1) while maintaining a constant running speed of 10 kph.
      Throughout all the trials, VO2 was determined on a breath-by-breath basis using a
      precalibrated metabolic cart. The criteria adopted for determination of a plateau
      was a Delta VO2 over the final two consecutive 30-s sampling periods of <=50 ml .
      min(-1). Averaging across the two trials per each exercise modality showed a
      significant difference for plateau incidence between CYC (8%) and TRE (58%) (P =
      0.017). This was aligned with a significant difference in the slope of the
      regression line during the final 60 s of the VO2max test, CYC (99.9 +/- 49.7 ml .
      min(-1)) and TRE (49.6 +/- 42.6 ml . min(-1)) (P = 0.017). Repeat measures ANOVA
      of these data suggests that plateau incidence rates at VO2max differ between
      treadmill- and cycle ergometry-based exercises. Future studies need to address
      whether these response rates are replicated in well-trained athletes.

PMID- 22856348
TI  - Echogenicity of the carotid intima-media complex and cardiovascular risk factors.
AB  - INTRODUCTION: Increased carotid intima-media thickness (IMT) has been associated
      with increased risk of myocardial infarction (MI) and stroke. A measure of
      echogenicity, the grey scale median (GSM), has been shown to be inversely
      correlated with cardiovascular risk factors and to be predictive of mortality in
      a community-based cohort. We assessed the factors associated with carotid IM-GSM
      in younger, non-diabetic patients with a recent MI. METHODS AND RESULTS: A total
      of 122 patients (women, 25%) aged 31-80 years (61) were recruited 2-3 days after
      an acute MI. Ultrasound examinations of the carotid arteries were performed 1-12
      months after the MI. IMT was 0.78 (SD 0.17) mm on the right side and 0.81 (0.20)
      mm on the left side (P = 0.05). GSM was 88.60 (range 46-132, SD 18.32) on the
      right side and 82.10 (40-126, 17.89) on the left side (P = 0.002). Triglycerides
      (TG) correlated with GSM on both sides (right, r = -0.27, P = 0.003; left, r = 
      0.18, P = 0.05). On the right side, GSM was 92.15 and 82.26 (P = 0.05) in
      patients with TG < and >=1.7, and on the left side, it was 84.04 and 74.55 (P =
      0.02) in patients with TG < and >=2.3. On multivariate analysis, TG were
      significantly associated with GSM, both on the right side (P = 0.01) and on the
      left side (P = 0.009). CONCLUSION: We found a negative association between TG and
      carotid IM-GSM on both sides in patients with a recent MI. Our results also
      suggest that atherosclerosis progression may be faster on the left side in
      patients with coronary heart disease.

PMID- 22856349
TI  - Plasma nitrite concentration decreases after hyperoxia-induced oxidative stress
      in healthy humans.
AB  - The aim of this study was to measure plasma nitrite, the biochemical marker of
      endothelial nitric oxide ((*)NO) synthesis, before and after hyperoxia, in order
      to test the hypothesis that hyperoxia-induced vasoconstriction is a consequence
      of reduced bioavailability of (*)NO caused by elevated oxidative stress. Ten
      healthy men breathed 100% normobaric O(2) for 30 min between 15th and 45th min of
      the 1-h study protocol. Plasma nitrite and malondialdehyde (MDA), arterial
      stiffness (indicated by augmentation index, AIx) and arterial oxygen (P(tc)O(2))
      pressure were measured at 1st, 15th, 45th and 60th minute of the study. Breathing
      of normobaric 100% oxygen during 30 min caused an increase in P(tc)O(2) (from 75
      +/- 2 to 412 +/- 25 mm Hg), AIx (from -63 +/- 4 to -51 +/- 3%) and MDA (from 152
      +/- 13 to 218 +/- 15 nm) values and a decrease in plasma nitrite (from 918 +/- 58
      to 773 +/- 55 nm). During the 15-min recovery phase, plasma nitrite, AIx and MDA
      values remained altered. This study suggests that the underlying mechanism of
      hyperoxia-induced vasoconstriction may involve reduced (*)NO bioavailability
      caused by elevated and sustained oxidative stress.

PMID- 22856350
TI  - Shoulder sensorimotor control assessment by force platform: feasibility and
      reliability.
AB  - Given the important role of the shoulder sensorimotor system in shoulder
      stability, its assessment appears of interest. Force platform monitoring of
      centre of pressure (CoP) in upper-limb weight-bearing positions is of interest as
      it allows integration of all aspects of shoulder sensorimotor control. This study
      aimed to determine the feasibility and reliability of shoulder sensorimotor
      control assessment by force platform. Forty-five healthy subjects performed two
      sessions of CoP measurement using Win-Posturo((r))  Medicapteurs force platform
      in an upper-limb weight-bearing position with the lower limbs resting on a table
      to either the anterior superior iliac spines (P1) or upper patellar poles (P2).
      Four different conditions were tested in each position in random order: eyes open
      or eyes closed with trunk supported by both hands and eyes open with trunk
      supported on the dominant or non-dominant side. P1 reliability values were
      globally moderate to high for CoP length, CoP velocity and CoP standard deviation
      (SD), standard error of measurement ranged from 6.0% to 26.5%, except for CoP
      area. P2 reliability values were globally low and not clinically acceptable. Our
      results suggest that shoulder sensorimotor control assessment by force platform
      is feasible and has good reliability in upper-limb weight-bearing positions when
      the lower limbs are resting on a table to the anterior superior iliac spines. CoP
      length, CoP velocity and CoP SD velocity appear to be the most reliable
      variables.

PMID- 22856351
TI  - Discrepancies in accelerometer-measured physical activity in children due to cut
      point non-equivalence and placement site.
AB  - This study examined dissonance in physical activity (PA) between two youth
      specific hip-derived intensity cut-points for the Actiwatch (AW), and compared PA
      between hip and wrist placements using site-specific cut-points. Twenty-four
      children aged 11.2 +/- 0.5 years wore the AW on the right hip and non-dominant
      wrist during a typical school day. Minutes of sedentary behaviour and vigorous
      activity were greater using Puyau et al. (2002) cut-points, but light, moderate,
      and moderate-to-vigorous (MVPA) were greater when derived using Puyau et al.
      (2004) cut-points (P < 0.01). Total hip activity counts were lower than wrist.
      Sedentary minutes were greater at the hip, but minutes of light, vigorous and
      MVPA were lower (P < 0.01). Moderate minutes were greater at the hip, but
      differed only when applying the Puyau et al. (2004) cut-points (P < 0.01). In
      conclusion, data comparisons between two hip derived AW cut-points and between
      hip and wrist data are inappropriate. Future researchers using the AW at the hip
      should present data reduced using both published cut-points. As hip and wrist
      data differ, the wrist placement is preferable as it will likely increase
      children's compliance to monitoring protocols due to reduced obtrusiveness
      compared to the hip.

PMID- 22856352
TI  - Spectroscopic study on the interaction of pristine C60 and serum albumins in
      solution.
AB  - The interaction of nanomaterials with biological macromolecules is an important
      foundation of the design and the biological safety assessments of nanomaterials.
      This work aims to investigate the interaction between pristine C60 and serum
      albumins (human serum albumin and bovine serum albumin) in solution. Stable
      aqueous dispersion of C60 was prepared by simple direct ultrasonic method and
      characterized by UV-vis spectrophotometry, transmission electronic microscopy and
      dynamic light scattering techniques, and spectroscopic methods (fluorescence
      spectroscopy, synchronous fluorescence spectroscopy and circular dichroism
      spectroscopy) were utilized for the investigation. It was found that the
      fluorescence of serum albumins could be quenched by C60 nanoparticles in a
      substantially similar way. Slight changes of the surrounding microenvironment of
      amino residues were observed, while little effects on the protein secondary
      structure occurred. The different effects of dispersion methods on the
      interaction of C60 nanoparticles with serum protein were also compared and
      discussed.

PMID- 22856353
TI  - Monozygotic twins discordant for port wine stains support the post-zygotic
      mutation hypothesis.

PMID- 22856355
TI  - The potential usefulness of free fetal DNA in maternal blood for prenatal fetal
      gender determination in multiple pregnancies.
AB  - We applied a noninvasive prenatal test for the determination of fetal gender in
      multiple pregnancies by using free fetal DNA circulating in maternal blood in
      order to evaluate whether the quantification of male DNA could distinguish the
      fetal gender and the number of male and female fetuses in multiple pregnancies.
      We enrolled consecutively 44 women with twin pregnancies between 11-14 weeks of
      gestation. Peripheral maternal blood was collected, and genomic DNA was extracted
      from maternal plasma and analyzed for the multicopy DYS 14 sequence by using real
      time PCR to quantify male DNA. Results showed that male DNA concentration was
      significantly higher in twin pregnancies with at least one male fetus, compared
      to twin pregnancies with only female fetuses. Comparing male DNA concentration in
      pregnancies with two male fetuses versus pregnancies with one female fetus and
      one male fetus, we did not obtain a significant difference between the two groups
      due to a slight overlapping of the range values. Therefore, our test correctly
      predicted fetal gender, distinguishing twin pregnancies with at least one male
      fetus from twin pregnancies with only female fetuses, with a diagnostic accuracy
      of 100%. For distinguishing pregnancies with two male fetuses from pregnancies
      with both female and male fetuses, a diagnostic accuracy of 76.1% was achieved.

PMID- 22856354
TI  - The use of nasal epithelial stem/progenitor cells to produce functioning ciliated
      cells in vitro.
AB  - BACKGROUND: Although epithelial stem/progenitor cells have been isolated from
      many parts of the human airway epithelium such as lung and trachea, there is
      limited information in regard to stem cells in nasal epithelium. The aim of this
      study was to determine if (1) human  nasal epithelial stem/progenitor cells
      (hNESPCs) can be isolated and propagated in vitro and (2) allogeneic adult
      primary human fibroblasts can serve as a feeder layer for hNESPCs expansion under
      serum-free conditions. METHODS: Primary cells taken from inferior turbinate 
      biopsy specimens (n = 3) were enzymically dissociated and plated on either
      allogeneic human fibroblasts or murine NIH 3T3 fibroblasts, in a chemical-defined
      medium supplemented with growth factors. Self-renewal, proliferation, and
      differentiation potential were compared. RESULTS: The optimized media were
      capable of supporting the undifferentiated growth and expansion of hNESPCs on
      both feeder cells. The doubling time and cloning efficiency of hNESPCs cultured
      on a human feeder layer were comparable with that cultured on 3T3 feeders.
      Significantly, the hNESPCs on  both feeder layers could be cultured for four
      passages, and they can differentiate into ciliated columnar cells and goblet
      cells at the air-liquid interface, resembling the in vivo mucociliary airway
      epithelium. CONCLUSION: Our results showed the feasibility  of expanding hNESPCs
      for clinical purpose by using human feeder layer, avoiding components of animal
      source, while preserving their self-renewal and differentiation potential. This
      study represents an early step toward a better understanding of hNESPCs, and
      serum -free media plus human feeder  potentially would be an ideal method for
      making clinical grade hNESPCs on a large scale.

PMID- 22856356
TI  - Effects of chorionicity and zygosity on triplet birth weight.
AB  - Birth weight in triplets is, on average, lower than in singletons and twins, and
      more children are classified as having very low or extremely low birth weight.
      Still, there is limited research on factors that affect triplet birth weight, and
      samples under study are often small. Chorionicity and zygosity influence triplet
      birth weight, but it is unknown whether the effect of zygosity can be entirely
      ascribed to the effect of chorionicity or whether zygosity has an additional
      effect on triplet birth weight. This question was investigated in 346 triplets
      (from 116 trios) registered with the Netherlands Twin Register for whom data on
      chorionicity were available. 'Triplet' refers to one child and the set of three
      triplets is referred to as 'trio'. Trios and triplets were classified based on
      zygosity and chorionicity. With regression analysis, the effects of zygosity and
      chorionicity on triplet birth weight were examined, while controlling for
      gestational age, sex, and maternal smoking during pregnancy. In addition, within
      the dizygotic trios a within-family comparison was made between the birth weight
      of the triplets that were part of a monozygotic pair (with some pairs sharing a
      chorion), and the birth weight of the dizygotic triplet. Based on the
      classification on individual level, monozygotic, monochorionic triplets had a
      lower mean birth weight than dizygotic, dichorionic triplets. Most remarkably, in
      dizygotic trios, monozygotic pairs only had a lower mean birth weight than their
      dizygotic sibling triplet when the pair shared a chorion. We conclude that having
      shared a chorion, rather than being monozygotic, increases the risk of a low
      birth weight.

PMID- 22856357
TI  - Causes of comorbidity: pleiotropy or causality? Shared genetic and environmental
      influences on migraine and neuroticism.
AB  - Comorbidity - the clustered occurrence of two traits or disorders - may be
      studied in genetically informative designs such as the classical twin study, to
      test whether genetic and/or environmental factors underlying the two disorders
      are correlated. When a genetic correlation is found, this can be explained by
      several mechanisms, including pleiotropy (the same genes influencing multiple
      traits), and causality (one trait causing the other). With a cotwin control
      design, it can be investigated which scenario is most plausible. In this design,
      monozygotic twin pairs discordant for the first trait (i.e., one twin is
      affected, the other is not) are compared in terms of their risk for the second
      trait: under a causal model, only the twins affected for the first trait will be
      at increased risk for the second trait. Under genetic pleiotropy, this risk will
      be increased in both twins because they share the same risk genes. We first
      discuss the cotwin control design and then illustrate its application with data
      on migraine and neuroticism that were collected in 5,200 Dutch twins, including
      1,648 complete twin pairs (981 monozygotic and 667 dizygotic pairs). There was a
      significant association between migraine and neuroticism, which could be
      attributed to genetic and environmental correlations (rG = .27 and rE = .19). In
      monozygotic and dizygotic twin pairs discordant for neuroticism, the risk of
      migraine was significantly higher in the twins with a high neuroticism score.
      This pattern of results is consistent with a causal relationship, suggesting that
      neuroticism increases the risk of migraine.

PMID- 22856358
TI  - Feeling of cold hands and feet is a highly heritable phenotype.
AB  - The prevalence of the feeling of cold hands and feet (FCHF) is high in the
      general population but the etiology of FCHF is largely unknown. The aim of the
      present study was to explore whether the FCHF is heritable. Eight hundred and
      ninety-four pairs of twins completed a question about FCHF. Tetrachoric
      correlations for FCHF were .58, .29, .67, .52, and .04 for monozygotic male,
      dizygotic male, monozygotic female, and dizygotic female twins, respectively.
      Model-fitting analyses suggested that in the best fitting model, additive genetic
      and nonshared environmental variance including measurement error were 64% (95%
      CI: 55%-72%) and 36% (28%-45%), respectively. Sex differences in genetic and
      environmental influences were not significant.

PMID- 22856360
TI  - Organ donation: a twin-based perspective.
AB  - Monozygotic cotwins are ideal organ donors for one another due to their genetic
      identity. The present report treats this topic differently, from the perspective
      of a monozygotic twin who donated her deceased twin sister's organs following her
      sister's untimely death. This discussion is followed by reviews of recent
      research concerning increased twinning rates in the United States, availability
      of informative kinship pedigrees, and twin discordance for physical activities.
      Noteworthy news items include ethical issues surrounding conjoined twin
      separation, a genomic discovery for diseased twins, China's One-Child Policy, a
      striking New Yorker Magazine cartoon, and twin delivery complications.

PMID- 22856362
TI  - Neuroimaging and genetics: exploring, searching, and finding.

PMID- 22856363
TI  - Associations between variants near a monoaminergic pathways gene (PHOX2B) and
      amygdala reactivity: a genome-wide functional imaging study.
AB  - As the amygdala is part of the phylogenetic old brain, and its anatomical and
      functional properties are conserved across species, it is reasonable to assume
      genetic influence on its activity. A large corpus of candidate gene studies
      indicate that individual differences in amygdala activity may be caused by
      genetic variants within monoaminergic signaling pathways such as dopamine,
      serotonin, and norepinephrine. However, to our knowledge, the use of genome-wide
      data to discover genetic variants underlying individual differences in adult
      amygdala activity is novel. In the present study, the combination of genome-wide
      data and functional imaging phenotypes from an emotional faces task yielded a
      significant association between rs10014254 and the amygdala using a region of
      interest approach. This single nucleotide polymorphism is located in a regulatory
      region upstream of the Paired-like homeobox 2b (PHOX2B) gene; therefore it could
      affect the expression of this gene. PHOX2B regulates the expression of enzymes
      necessary for the synthesis of several monoamines and is essential for the
      development of the autonomic nervous system. However, an attempt to replicate the
      finding in an independent sample from North America did not succeed. The
      synthesis of functional magnetic resonance imaging (fMRI) and genome-wide data
      takes a hypothesis-free approach as to which genetic variants are of interest.
      Therefore, we believe that an undirected finding within such a plausible region
      is of interest, and that our results add further support to the hypothesis that
      monoaminergic signaling pathways play a central role in regulating amygdala
      activity.

PMID- 22856364
TI  - Alzheimer's disease risk gene, GAB2, is associated with regional brain volume
      differences in 755 young healthy twins.
AB  - The development of late-onset Alzheimer's disease (LOAD) is under strong genetic
      control and there is great interest in the genetic variants that confer increased
      risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2
      associated protein (GAB2), has been shown to provide a 1.27-1.51 increased odds
      of developing LOAD for rs7101429 major allele carriers, in case-control analysis.
      GAB2 is expressed across the brain throughout life, and its role in LOAD
      pathology is well understood. Recent studies have begun to examine the effect of
      genetic variation in the GAB2 gene on differences in the brain. However, the
      effect of GAB2 on the young adult brain has yet to be considered. Here we found a
      significant association between the GAB2 gene and morphological brain differences
      in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene
      based test with principal components regression (PCReg). Detectable differences
      in brain morphology are therefore associated with variation in the GAB2 gene,
      even in young adults, long before the typical age of onset of Alzheimer's
      disease.

PMID- 22856365
TI  - The effect of the neurogranin schizophrenia risk variant rs12807809 on brain
      structure and function.
AB  - A single nucleotide polymorphism rs12807809 located upstream of the neurogranin
      (NRGN) gene has been identified as a risk variant for schizophrenia in recent
      genome-wide association studies. To date, there has been little investigation of
      the endophenotypic consequences of this variant, and our own investigations have
      suggested that the effects of this gene are not apparent at the level of
      cognitive function in patients or controls. Because the impact of risk variants
      may be more apparent at the level of brain, the aim of this investigation was to
      delineate whether NRGN genotype predicted variability in brain structure and/or
      function. Healthy individuals participated in structural (N = 140) and/or
      functional (N = 36) magnetic resonance imaging (s/fMRI). Voxel-based morphometry
      was used to compare gray and white matter volumes between carriers of the non
      risk C allele (i.e., CC/CT) and those who were homozygous for the risk T allele.
      Functional imaging data were acquired during the performance of a spatial working
      memory task, and were also analyzed with respect to the difference between C
      carriers and T homozygotes. There was no effect of the NRGN variant rs12807809 on
      behavioral performance or brain structure. However, there was a main effect of
      genotype on brain activity during performance of the working memory task, such
      that while C carriers exhibited a load-independent decrease in left superior
      frontal gyrus/BA10, TT individuals failed to show a similar decrease in activity.
      The failure to disengage this ventromedial prefrontal region, despite preserved
      performance, may be indicative of a reduction in processing efficiency in healthy
      TT carriers. Although it remains to be established whether this holds true in
      larger samples and in patient cohorts, if valid, this suggests a potential
      mechanism by which NRGN variability might contribute to schizophrenia risk.

PMID- 22856366
TI  - A comparison of heritability maps of cortical surface area and thickness and the
      influence of adjustment for whole brain measures: a magnetic resonance imaging
      twin study.
AB  - Understanding the genetic and environmental contributions to measures of brain
      structure such as surface area and cortical thickness is important for a better
      understanding of the nature of brain-behavior relationships and changes due to
      development or disease. Continuous spatial maps of genetic influences on these
      structural features can contribute to our understanding of regional patterns of
      heritability, since it remains to be seen whether genetic contributions to brain
      structure respect the boundaries of any traditional parcellation approaches.
      Using data from magnetic resonance imaging scans collected on a large sample of
      monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we
      created maps of the heritability of areal expansion (a vertex-based area measure)
      and cortical thickness and examined the degree to which these maps were affected
      by adjustment for total surface area and mean cortical thickness. We also
      compared the approach of estimating regional heritability based on the average
      heritability of vertices within the region to the more traditional region-of
      interest (ROI)-based approach. The results suggested high heritability across the
      cortex for areal expansion and, to a slightly lesser degree, for cortical
      thickness. There was a great deal of genetic overlap between global and regional
      measures for surface area, so maps of region-specific genetic influences on
      surface area revealed more modest heritabilities. There was greater inter
      regional variability in heritabilities when calculated using the traditional ROI
      based approach compared to summarizing vertex-by-vertex heritabilities within
      regions. Discrepancies between the approaches were greatest in small regions and
      tended to be larger for surface area than for cortical thickness measures.
      Implications regarding brain phenotypes for future genetic association studies
      are discussed.

PMID- 22856367
TI  - Genetic contributions to the midsagittal area of the corpus callosum.
AB  - The degree to which genes and environment determine variations in brain structure
      and function is fundamentally important to understanding normal and disease
      related patterns of neural organization and activity. We studied genetic
      contributions to the midsagittal area of the corpus callosum (CC) in pedigreed
      baboons (68 males, 112 females) to replicate findings of high genetic
      contribution to that area of the CC reported in humans, and to determine if the
      heritability of the CC midsagittal area in adults was modulated by fetal
      development rate. Measurements of callosal area were obtained from high
      resolution MRI scans. Heritability was estimated from pedigree-based maximum
      likelihood estimation of genetic and non-genetic variance components as
      implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Our
      analyses revealed significant heritability for the total area of the CC and all
      of its subdivisions, with h2 = .46 for the total CC, and h2 = .54, .37, .62, .56,
      and .29 for genu, anterior midbody, medial midbody, posterior midbody and
      splenium, respectively. Genetic correlation analysis demonstrated that the
      individual subdivisions shared between 41% and 98% of genetic variability.
      Combined with previous research reporting high heritability of other brain
      structures in baboons, these results reveal a consistent pattern of high
      heritability for brain morphometric measures in baboons.

PMID- 22856368
TI  - Heritability of multivariate gray matter measures in schizophrenia.
AB  - Structural brain measures are employed as endophenotypes in the search for
      schizophrenia susceptibility genes. We analyzed two independent structural
      imaging datasets with voxel-based morphometry and with source-based morphometry,
      a multivariate, independent components analysis, to determine the stability and
      heritability of regional gray matter concentration abnormalities in
      schizophrenia. The samples comprised 209 and 102 patients with schizophrenia and
      208 and 96 healthy volunteers, respectively. The second sample additionally
      included non-ill siblings of participants with and without schizophrenia. A
      standard voxel-based analysis showed reproducible regional gray matter deficits
      in the affected participants compared with unrelated, unaffected controls in both
      datasets: patients showed significant gray matter concentration deficits in
      cortical frontal, temporal, and insular lobes. Source-based morphometry (SBM) was
      applied to the gray matter images of the entire sample to determine the effects
      of diagnosis on networks of covarying structures. The SBM analysis extracted 24
      significant sets of covarying regions (components). Four of these components
      showed significantly lower gray matter concentrations in patients (p < .05). We
      determined the familiality of the observed SBM components based on 66 sibling
      pairs (25 discordant for schizophrenia). Two components, one including the medial
      frontal, insular, inferior frontal, and temporal lobes, and the other including
      the posterior occipital lobe, showed significant familiality (p < .05). We
      conclude that structural brain deficits in schizophrenia are replicable, and that
      SBM can extract unique familial and likely heritable components. SBM provides a
      useful data reduction technique that can provide measures that may serve as
      endophenotypes for schizophrenia.

PMID- 22856369
TI  - White matter heritability using diffusion tensor imaging in neonatal brains.
AB  - Understanding genetic and environmental effects on white matter development in
      the first years of life is of great interest, as it provides insights into the
      etiology of neurodevelopmental disorders. In this study, the genetic and
      environmental effects on white matter were estimated using data from 173 neonatal
      twin subjects. Diffusion tensor imaging scans were acquired around 40 days after
      birth and were non-rigidly registered to a group-specific atlas and parcellated
      into 98 ROIs. A model of additive genetic, and common and specific environmental
      variance components was used to estimate overall and regional genetic and
      environmental contributions to diffusion parameters of fractional anisotropy,
      radial diffusivity, and axial diffusivity. Correlations between the regional
      heritability values and diffusion parameters were also examined. Results indicate
      that individual differences in overall white matter microstructure, represented
      by the average diffusion parameters over the whole brain, are heritable, and
      estimates are higher than found in studies in adults. Estimates of genetic and
      environmental variance components vary considerably across different white matter
      regions. Significant positive correlations between radial diffusivity
      heritability and radial diffusivity values are consistent with regional genetic
      variation being modulated by maturation status in the neonatal brain: the more
      mature the region is, the less genetic variation it shows. Common environmental
      effects are present in a few regions that tend to be characterized by low radial
      diffusivity. Results from the joint diffusion parameter analysis suggest that
      multivariate modeling approaches might be promising to better estimate maturation
      status and its relationship with genetic and environmental effects.

PMID- 22856371
TI  - Brain activation during response interference in twins discordant or concordant
      for obsessive compulsive symptoms.
AB  - One of the core behavioral features associated with obsessive compulsive
      symptomatology is the inability to inhibit thoughts and/or behaviors.
      Neuroimaging studies have indicated abnormalities in frontostriatal and
      dorsolateral prefrontal - anterior cingulate circuits during inhibitory control
      in patients with obsessive compulsive disorder compared with controls. In the
      present study, task performance and brain activation during Stroop color-word and
      Flanker interference were compared within monozygotic twin pairs discordant for
      obsessive compulsive symptoms and between groups of pairs scoring very low or
      very high on obsessive compulsive symptoms, in order to examine the differential
      impact of non-shared environmental versus genetic risk factors for obsessive
      compulsive symptomatology on inhibitory control related functional brain
      activation. Although performance was intact, brain activation during inhibition
      of distracting information differed between obsessive compulsive symptom high
      scoring compared to low-scoring subjects. Regions affected in the discordant
      group (e.g., temporal and anterior cingulate gyrus) were partly different from
      those observed to be affected in the concordant groups (e.g., parietal gyrus and
      thalamus). A robust increase in dorsolateral prefrontal activity during response
      interference was observed in both the high-scoring twins of the discordant sample
      and the high-scoring twins of the concordant sample, marking this structure as a
      possible key region for disturbances in inhibitory control in obsessive
      compulsive disorder.

PMID- 22856370
TI  - Genetic and environmental influences on neuroimaging phenotypes: a meta
      analytical perspective on twin imaging studies.
AB  - Because brain structure and function are affected in neurological and psychiatric
      disorders, it is important to disentangle the sources of variation in these
      phenotypes. Over the past 15 years, twin studies have found evidence for both
      genetic and environmental influences on neuroimaging phenotypes, but considerable
      variation across studies makes it difficult to draw clear conclusions about the
      relative magnitude of these influences. Here we performed the first meta-analysis
      of structural MRI data from 48 studies on >1,250 twin pairs, and diffusion tensor
      imaging data from 10 studies on 444 twin pairs. The proportion of total variance
      accounted for by genes (A), shared environment (C), and unshared environment (E),
      was calculated by averaging A, C, and E estimates across studies from independent
      twin cohorts and weighting by sample size. The results indicated that additive
      genetic estimates were significantly different from zero for all meta-analyzed
      phenotypes, with the exception of fractional anisotropy (FA) of the callosal
      splenium, and cortical thickness (CT) of the uncus, left parahippocampal gyrus,
      and insula. For many phenotypes there was also a significant influence of C. We
      now have good estimates of heritability for many regional and lobar CT measures,
      in addition to the global volumes. Confidence intervals are wide and number of
      individuals small for many of the other phenotypes. In conclusion, while our meta
      analysis shows that imaging measures are strongly influenced by genes, and that
      novel phenotypes such as CT measures, FA measures, and brain activation measures
      look especially promising, replication across independent samples and demographic
      groups is necessary.

PMID- 22856372
TI  - Individual differences in EEG spectral power reflect genetic variance in gray and
      white matter volumes.
AB  - The human electroencephalogram (EEG) consists of oscillations that reflect the
      summation of postsynaptic potentials at the dendritic tree of cortical neurons.
      The strength of the oscillations (EEG power) is a highly genetic trait that has
      been related to individual differences in many phenotypes, including intelligence
      and liability for psychopathology. Here, we investigated whether brain anatomy
      underlies these EEG power differences by correlating it to gray and white matter
      volumes (GMV, WMV), and additionally investigated whether this association can be
      attributed to genes or environmental factors. EEG was measured in a sample of 405
      young adult twins and their siblings, and power in the theta (~4 Hz), alpha (~10
      Hz), and beta (~20 Hz) frequency bands determined. A subset of 121 subjects were
      also scanned in a 1.5 T MRI scanner, and gray and white matter volumes defined as
      the total of cortical and subcortical volumes, excluding cerebellum. Both MRI
      based volumes and EEG power spectra were highly heritable. GMV and WMV correlated
      .25 to .29 with EEG power for the slower oscillations (theta, alpha). Moreover,
      these phenotypic correlations largely reflected genetic covariation, irrespective
      of oscillation frequency and volume type. Genetic correlations (.31 < rA < .43)
      revealed that only moderate proportions of the heritable variance overlapped
      between MRI volumes and EEG power. The results suggest that MRI volumes and EEG
      power share genetic sources of variation, which may reflect such processes as
      myelination, synaptic density, and dendritic outgrowth.

PMID- 22856373
TI  - Estimation of subject-specific heritabilities from intra-individual variation:
      iFACE.
AB  - A new genetic factor model for multivariate phenotypic time series, iFACE, is
      presented which allows for the estimation of subject-specific model parameters of
      genetic and environmental factors. The iFACE was applied to multivariate EEG
      registrations obtained with single dizygotic twin pairs. The results showed
      evidence for considerable subject-specificity in heritabilities and environmental
      effects. The assumption that the population is homogeneous (i.e., that each case
      in the population obeys the same parametric model), does not hold for these
      psychophysiological data, and its use should be critically reconsidered. We
      conclude that the iFACE provides a powerful new methodology to assess
      heterogeneity (subject-specificity) based on phenotypic observations.

PMID- 22856374
TI  - Cerebral asymmetry: a quantitative, multifactorial, and plastic brain phenotype.
AB  - The longitudinal fissure separates the human brain into two hemispheres that
      remain connected through the corpus callosum. The left and the right halves of
      the brain resemble each other, and almost every structure present in one side has
      an equivalent structure in the other. Despite this exceptional correspondence,
      the two hemispheres also display important anatomical differences and there is
      marked lateralization of certain cognitive and motor functions such as language
      and handedness. However, the mechanisms that underlie the establishment of these
      hemispheric specializations, as well as their physiological and behavioral
      implications, remain largely unknown. Thanks to recent advances in neuroimaging,
      a series of studies documenting variation in symmetry and asymmetry as a function
      of age, gender, brain region, and pathological state, have been published in the
      past decade. Here, we review evidence of normal and atypical cerebral asymmetry,
      and the factors that influence it at the macrostructural level. Given the
      prominent role that cerebral asymmetry plays in the organization of the brain,
      and its possible implication in neurodevelopmental and psychiatric conditions,
      further research in this area is anticipated.

PMID- 22856375
TI  - EnigmaVis: online interactive visualization of genome-wide association studies of
      the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium.
AB  - In an attempt to increase power to detect genetic associations with brain
      phenotypes derived from human neuroimaging data, we recently conducted a large
      scale, genome-wide association meta-analysis of hippocampal, brain, and
      intracranial volume through the Enhancing NeuroImaging Genetics through Meta
      Analysis (ENIGMA) consortium. Here, we present a freely available online
      interactive tool, EnigmaVis, which makes it easy to visualize the association
      results generated by the consortium alongside allele frequency, genes, and
      functional annotations. EnigmaVis runs natively within the web browser, and
      generates plots that show the level of association between brain phenotypes at
      user-specified genomic positions. Uniquely, EnigmaVis is dynamic; users can
      interact with elements on the plot in real time. This software will be useful
      when exploring the effect on brain structure of particular genetic variants
      influencing neuropsychiatric illness and cognitive function. Future projects of
      the consortium and updates to EnigmaVis will also be displayed on the site.
      EnigmaVis is freely available online at http://enigma.loni.ucla.edu/enigma-vis/

PMID- 22856376
TI  - The TWIN-E project in emotional wellbeing: study protocol and preliminary
      heritability results across four MRI and DTI measures.
AB  - Despite the significant advancements being made in the neurogenetics for mental
      health, the identification and validation of potential endophenotype markers of
      risk and resilience remain to be confirmed. The TWIN-E study (The Twin study in
      Wellbeing using Integrative Neuroscience of Emotion) aims to validate
      endophenotype markers of mental health across cognitive, brain, and autonomic
      measures by testing the heritability, clinical plausibility, and reliability of
      each of these measures in a large adult twin cohort. The specific gene and
      environmental mechanisms that moderate prospective links between endophenotype
      phenotype markers and the final outcome of wellbeing will also be identified.
      TWIN-E is a national prospective study with three phases: I) baseline testing on
      a battery of online questionnaires and cognitive tasks, and EEG, MRI, and
      autonomic testing; II) 12-month follow-up testing on the online assessments; and
      III) randomized controlled trial of brain training. Minimum target numbers
      include 1,500 male/female twins (18-65 years) for the online assessments (Phase I
      and II), 300 twins for the EEG testing component, and 244 twins for the MRI
      testing component. For Phase III, each twin out of the pair will be randomized to
      either the treatment or waitlist control group to test the effects of brain
      training on mental health over a 30-day period, and to confirm the gene
      environment and endophenotype contributions to treatment response. Preliminary
      heritability results are provided for the first 50% of the MRI subgroup (n = 142)
      for the grey matter volume, thickness, and surface area measures, and white
      matter diffuse tensor imaging fractional anisotropy.

PMID- 22856377
TI  - Imaging and cognitive genetics: the Norwegian Cognitive NeuroGenetics sample.
AB  - Data collection for the Norwegian Cognitive NeuroGenetics sample (NCNG) was
      initiated in 2003 with a research grant (to Ivar Reinvang) to study cognitive
      aging, brain function, and genetic risk factors. The original focus was on the
      effects of aging (from middle age and up) and candidate genes (e.g., APOE,
      CHRNA4) in cross-sectional and longitudinal designs, with the cognitive and MRI
      based data primarily being used for this purpose. However, as the main topic of
      the project broadened from cognitive aging to imaging and cognitive genetics more
      generally, the sample size, age range of the participants, and scope of available
      phenotypes and genotypes, have developed beyond the initial project. In 2009, a
      genome-wide association (GWA) study was undertaken, and the NCNG proper was
      established to study the genetics of cognitive and brain function more
      comprehensively. The NCNG is now controlled by the NCNG Study Group, which
      consists of the present authors. Prominent features of the NCNG are the adult
      life-span coverage of healthy participants with high-dimensional imaging, and
      cognitive data from a genetically homogenous sample. Another unique property is
      the large-scale (sample size 300-700) use of experimental cognitive tasks
      focusing on attention and working memory. The NCNG data is now used in numerous
      ongoing GWA-based studies and has contributed to several international consortia
      on imaging and cognitive genetics. The objective of the following presentation is
      to give other researchers the information necessary to evaluate possible
      contributions from the NCNG to various multi-sample data analyses.

PMID- 22856378
TI  - Brain SCALE: brain structure and cognition: an adolescent longitudinal twin study
      into the genetic etiology of individual differences.
AB  - From childhood into adolescence, the child's brain undergoes considerable changes
      in both structure and function. Twin studies are of great value to explore to
      what extent genetic and environmental factors explain individual differences in
      brain development and cognition. In The Netherlands, we initiated a longitudinal
      study in which twins, their siblings and their parents are assessed at three year
      intervals. The participants were recruited from The Netherlands Twin Register
      (NTR) and at baseline consisted of 112 families, with 9-year-old twins and an
      older sibling. Three years later, 89 families returned for follow-up assessment.
      Data collection included psychometric IQ tests, a comprehensive
      neuropsychological testing protocol, and parental and self-ratings of behavioral
      and emotional problems. Physical maturation was measured through assessment of
      Tanner stages. Hormonal levels (cortisol, luteinizing hormone, follicle
      stimulating hormone, testosterone, and estrogens) were assessed in urine and
      saliva. Brain scans were acquired using 1.5 Tesla Magnetic Resonance Imaging
      (MRI), which provided volumetric measures and measures of cortical thickness.
      Buccal swabs were collected for DNA isolation for future candidate gene and
      genome-wide analysis studies. This article gives an overview of the study and the
      main findings. Participants will return for a third assessment when the twins are
      around 16 years old. Longitudinal twin-sibling studies that map brain development
      and cognitive function at well-defined ages aid in the understanding of genetic
      influences on normative brain development.

PMID- 22856379
TI  - Solvent exposure and Parkinson's disease: co-twin control study.

PMID- 22856382
TI  - Race/ethnicity-, gender- and age-specific differences in micronutrient intakes of
      US adults with and without diabetes.
AB  - Race/ethnicity-, gender- and age-specific differences in dietary micronutrient
      intakes of US adults >=  21 years were assessed from National Health and
      Nutrition Examination Survey, 2007-2008. The participants included Black non
      Hispanics, Mexican-American and White non-Hispanics who signed an informed
      consent form for the interview and who completed the in-person 24-h recall.
      Micronutrient intakes were based on the Institute of Medicines' classifications
      of recommended dietary allowances specific for age and gender. Likelihood of many
      micronutrient insufficiencies was associated with being female, over 65 years,
      having diabetes and minority status. Younger and female adults had a greater
      likelihood of iron insufficiency than male and older adults. These findings
      demonstrate the importance of considering the intersection of age, gender and
      race in setting policies for micronutrient deficiency screening, particularly in
      young female adults and minorities.

PMID- 22856383
TI  - Resveratrol in cholesterol metabolism and atherosclerosis.
AB  - Resveratrol, a natural polyphenol produced by plants in response to environmental
      stress, has received great attention during the past few years due to its
      beneficial roles in longevity and glucose homeostasis. Resveratrol has been found
      to display antioxidant, anti-inflammatory, antifibrotic, and cardioprotective
      properties. Resveratrol reduces platelet aggregation, induces vasorelaxation,
      limits endothelial activation, and modulates lipid and lipoprotein metabolism.
      Although the mechanisms of action of resveratrol have not been completely
      defined, there is evidence that some of the effects of resveratrol may be
      mediated via activation of sirtuin 1 and AMP-activated protein kinase and through
      inhibition of the pleiotropic transcription factor nuclear factor kappaB.
      Pathways proposed to underlie resveratrol-mediated cardioprotection include
      reduction of oxidative stress and activation of endothelial nitric oxide
      synthase. Adenosinergic mechanisms may play a role in its atheroprotective
      activity. The ability of the nutraceutical resveratrol to positively influence
      the future treatment of cardiovascular disease is discussed.

PMID- 22856384
TI  - Age-specific prevalence, incidence of new diagnoses, and drug treatment of
      attention-deficit/hyperactivity disorder in Germany.
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence and incidence
      of new diagnoses of attention-deficit/hyperactivity disorder (ADHD) and assess
      drug treatment of ADHD in the 3-17 year age group in Germany. METHOD: We analysed
      data from the German Pharmacoepidemiological Research Database (GePaRD) for the
      years 2004-2006. The GePaRD includes claim records of 14,000,000 members of four
      statutory health insurances, representing 17% of the German population. The
      assessment of ADHD diagnoses was based on International Classification of
      Diseases version 10 (ICD-10) codes in outpatient and hospital data. RESULTS: In
      2005, the age-standardized prevalence and incidence of new diagnoses were 2.5%
      and 9/1000 person-years, respectively. Both measures were 3-4 times higher for
      males than for females. Incidence of new ADHD diagnoses increased linearly up to
      the age of 8 years for boys and 9 years for girls and decreased abruptly
      thereafter. In the calendar quarter of the initial ADHD diagnosis, 9.4% (95%
      confidence interval [CI] 8.9-9.8%) received methylphenidate or atomoxetine and
      36.8% (95% CI 36.1-37.6%) received at least one prescription of either drug
      within the first year. Initiation of drug treatment and choice of drug were
      similar for both sexes. CONCLUSIONS: ADHD is a common condition among children
      and youth in Germany. There are substantial differences by sex in the prevalence
      and incidence of new ADHD diagnoses, but only a small difference in drug
      treatment among those diagnosed with ADHD. A relatively low percentage of
      children receives drug treatment in the first year after the initial diagnosis of
      ADHD.

PMID- 22856385
TI  - Susceptibility of mitochondrial electron-transport complexes to oxidative damage.
      Focus on cytochrome c oxidase.
AB  - Reactive oxygen species (ROS) are associated with a number of mitochondrial
      disorders. These include: ischemia/reperfusion injury, Parkinson's disease,
      Alzheimer's disease, neurodegenerative diseases, and other age-related
      degenerative changes. ROS can be generated at numerous sites within the cell, but
      the mitochondrial electron transport chain is recognized as the major source of
      intracellular ROS. Two mitochondrial electron-transfer complexes are major
      sources of ROS: complex I and complex III. Oxidative damage to either of these
      complexes, or to electron transport complexes that are in close proximity to
      these ROS sources, e.g., cytochrome c oxidase, would be expected to inhibit
      electron transport. Such inhibition would lead to increased electron leakage and
      more ROS production, much like the well-known effect of adding electron transport
      inhibitors. Recent studies reveal that ROS and lipid peroxidation products are
      effective inhibitors of the electron-transport complexes. In some cases,
      inactivation of enzymes correlates with chemical modification of only a small
      number of unusually reactive amino acids. In this article, we review current
      knowledge of ROS-induced alterations within three complexes: (1) complex IV; (2)
      complex III; and (3) complex I. Our goal is to identify "hot spots" within each
      complex that are easily chemically modified and could be responsible for ROS
      induced inhibition of the individual complexes. Special attention has been placed
      on ROS-induced damage to cardiolipin that is tightly bound to each of the inner
      membrane protein complexes. Peroxidation of the bound cardiolipin is thought to
      be particularly important since its close proximity and long residence time on
      the protein make it an especially effective reagent for subsequent ROS-induced
      damage to these proteins.

PMID- 22856386
TI  - Presenteeism according to healthy behaviors, physical health, and work
      environment.
AB  - The objective of this study is to identify the contribution that selected
      demographic characteristics, health behaviors, physical health outcomes, and
      workplace environmental factors have on presenteeism (on-the-job productivity
      loss attributed to poor health and other personal issues). Analyses are based on
      a cross-sectional survey administered to 3 geographically diverse US companies in
      2010. Work-related factors had the greatest influence on presenteeism (eg, too
      much to do but not enough time to do it, insufficient technological
      support/resources). Personal problems and financial stress/concerns also
      contributed substantially to presenteeism. Factors with less contribution to
      presenteeism included physical limitations, depression or anxiety, inadequate job
      training, and problems with supervisors and coworkers. Presenteeism was greatest
      for those ages 30-49, women, separated/divorced/widowed employees, and those with
      a high school degree or some college. Clerical/office workers and service workers
      had higher presenteeism. Managers and professionals had the highest level of
      presenteeism related to having too much to do but too little time to do it, and
      transportation workers had the greatest presenteeism because of physical health
      limitations. Lowering presenteeism will require that employers have realistic
      expectations of workers, help workers prioritize, and provide sufficient
      technological support. Financial stress and concerns may warrant financial
      planning services. Health promotion interventions aimed at improving nutrition
      and physical and mental health also may contribute to reducing presenteeism.

PMID- 22856387
TI  - Pharmacokinetic characterization of the novel TAZ modulator TM-25659 using a
      multicompartment kinetic model in rats and a possibility of its drug-drug
      interactions in humans.
AB  - This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in
      rats following intravenous and oral administration at dose ranges of 0.5-5 mg/kg
      and 2-10 mg/kg, respectively. Plasma protein binding, plasma stability, liver
      microsomal stability, CYP inhibition, and transport in Caco-2 cells were also
      evaluated. After intravenous injection, systemic clearance, steady-state volumes
      of distribution, and half-life were dose-independent, with values ranging from
      0.434-0.890 mL . h(-1) . kg(-1), 2.02-4.22 mL/kg, and 4.60-7.40 h, respectively.
      Mean absolute oral bioavailability was 50.9% and was not dose dependent. Recovery
      of TM-25659 was 43.6% in bile and <1% in urine. In pharmacokinetic modeling
      studies, the three-compartment (3C) model was appropriate for understanding these
      parameters in rats. TM-25659 was stable in plasma. Plasma protein binding was
      approximately 99.2%, and was concentration-independent. TM-25659 showed high
      permeation of Caco-2 cells and did not appear to inhibit CYP450. TM-25659 was
      metabolized in phase I and II steps in rat liver microsomes. In conclusion, the
      pharmacokinetics of TM-25659 was characterized for intravenous and oral
      administration at doses of 0.5-5 and 2-10 mg/kg, respectively. TM-25659 was
      eliminated primarily by hepatic metabolism and urinary excretion.

PMID- 22856388
TI  - The effect of playing tactics and situational variables on achieving score-box
      possessions in a professional soccer team.
AB  - The aim of this study was to analyse the influence of playing tactics, opponent
      interaction and situational variables on achieving score-box possessions in
      professional soccer. The sample was constituted by 908 possessions obtained by a
      team from the Spanish soccer league in 12 matches played during the 2009-2010
      season. Multidimensional qualitative data obtained from 12 ordered categorical
      variables were used. Sampled matches were registered by the AMISCO PRO system.
      Data were analysed using chi-square analysis and multiple logistic regression
      analysis. Of 908 possessions, 303 (33.4%) produced score-box possessions, 477
      (52.5%) achieved progression and 128 (14.1%) failed to reach any sort of
      progression. Multiple logistic regression showed that, for the main variable
      "team possession type", direct attacks and counterattacks were three times more
      effective than elaborate attacks for producing a score-box possession (P < 0.05).
      Team possession originating from the middle zones and playing against less than
      six defending players (P < 0.001) registered a higher success than those started
      in the defensive zone with a balanced defence. When the team was drawing or
      winning, the probability of reaching the score-box decreased by 43 and 53
      percent, respectively, compared with the losing situation (P < 0.05). Accounting
      for opponent interactions and situational variables is critical to evaluate the
      effectiveness of offensive playing tactics on producing score-box possessions.

PMID- 22856389
TI  - Age-related changes in visual and auditory sustained attention in preschool-aged
      children.
AB  - OBJECTIVE: The development of sustained attention in the preschool years is not
      yet fully understood. Delineating age-related changes of attentional
      proficiencies and deficiencies is important for understanding atypical
      developmental trajectories, specifically in neurodevelopmental disorders that are
      characterized by attentional difficulties. The objective of the current study was
      to develop preschool-appropriate measures for assessing sustained attention and
      to chart developmental changes in attention in early childhood. METHOD: Using
      adapted computerized paradigms, the present study investigated age-related
      changes in visual and auditory sustained attention in seventy typically
      developing children aged 3 to 6 years. RESULTS: The results indicated that
      similar age-related gains in performance emerged across both visual and auditory
      attention tasks. CONCLUSION: The findings suggest that the adapted measures
      developed in this study are sensitive enough to capture developmental variations
      in attention performance.

PMID- 22856390
TI  - Multiple birth families with children with special needs: a qualitative
      investigation of mothers' experiences.
AB  - Multiple birth remains prevalent, with prematurity and subsequent disability
      being common complications. However, little is known of the experiences of
      mothers living with the combined circumstances of multiple birth, prematurity,
      and special needs. This paper reports an exploratory study using the qualitative
      technique of thematic analysis, to describe and interpret the experiences of 10
      mothers of prematurely born multiple birth children with diverse special needs.
      Mothers were shocked to learn they were carrying multiple fetuses, including
      those who underwent in vitro fertilization with dual embryo transfer. Most
      experienced protracted concern over one or more babies' survival during
      pregnancy, and prescribed bed rest was frequently associated with increased
      anxiety and other adverse psychological effects. Some experienced disenfranchised
      grief, such as those grieving the opportunity to bear a single child. The
      contrast with experiences of mothers of healthy, term singletons caused
      considerable distress. Feelings of detachment and unreality were common in the
      immediate postpartum period, possibly due to transient depersonalization. Having
      more than one newborn created practical and psychological problems during the
      neonatal period, particularly when infants were separated due to differences in
      medical status. The extent to which hospitals accommodated the multiple birth
      relationship varied and significantly affected mothers' postnatal experiences.
      Mothers often felt guilty, particularly regarding inequality of care and
      attention they were able to provide to each child. This was especially
      problematic for multiples discordant for special needs status. The presence of
      one normally developing child complicated adjustment to the other's difficulties,
      and several experienced chronic sorrow. Serious maternal mental health
      difficulties were common but not universal. Available formal supports were
      generally perceived as inadequate, addressing some, but not all, of the mothers'
      needs. Further work is needed to advance understanding of the relationships
      between mothers and their multiples, and to explore the implications of special
      needs within multiple birth families.

PMID- 22856394
TI  - Potentiating effects of honey on antioxidant properties of lemon-flavoured black
      tea.
AB  - Health benefits including antioxidant potential of black tea (Camellia sinensis),
      lemon (Citrus limon) and honey bees (Apis mellifera) have been extensively
      reported. Nevertheless, nothing is reported about the effects of their
      concomitant use. Herein, those effects were evaluated in infusions of lemon
      flavoured black tea with three different kinds of honey (light amber, amber and
      dark amber) from Lavandula stoechas, Erica sp. pl. and other indigenous floral
      species from north-east Portugal, a region with high amounts of this food
      product. Data obtained showed that the use of honey (dark amber>amber>light
      amber) potentiates the antioxidant activity of lemon-flavoured black tea,
      increasing the reducing power and lipid peroxidation inhibition properties, as
      also the antioxidant contents such as phenolics, flavonoids and organic acids
      including ascorbic acid.

PMID- 22856396
TI  - [Infective endarteritis complicating clinically silent patent ductus arteriosus].
AB  - Infective Endocarditis is caused by bacteria or fungi involving the heart or the
      great vessels (Endarteritis). It is a rare and potentially ominous disease, with
      increasing incidence. Despite technological advances it remains difficult to
      diagnose and treat, particularly in children below two years. Congenital heart
      disease is the main risk factor for Infective Endocarditis in children. A patent
      ductus arteriosus clinically silent is infrequently implied. Over two-month-old
      Streptococci spp and Staphylococcus aureus are the main agents, responsible for
      62-77% of cases. Gram negative rods count for 4-6%, being Klebsiella pneumoniae a
      rare pathogen. The authors report a case of a previously healthy four-months-old
      infant, admitted for bronchiolitis. He developed a Klebsiella pneumoniae
      persistent bacteremia related to Endarteritis of a silent patent ductus
      arteriosus. After prolonged and successful antibiotic therapy, the ductus
      arteriosus was surgically closed. He suffered no complication during the disease
      process and recovered uneventfully.

PMID- 22856397
TI  - [Hypoprothrombinemia--lupus anticoagulant syndrome].
AB  - Diagnosis criteria, pathogenic mechanisms, incidence and prevalence of the
      Antiphospholipid Syndrome are focused in a brief review. Hypoprothrombinemia
      (HPT) may be hereditary or acquired; the first is rare and with recessive
      autossomic transmission. We report the case of a 66-year-old white woman with
      Systemic Lupus Erythematosus (SLE), autoimmune haemolytic anaemia, periostitis,
      haematomas, bleeding leg ulcer and rectal haemorrhages; she had decreased levels
      of the prothrombin. Haemorrhagic episodes were related with the anti-prothrombin
      specificity of Lupus Anticoagulant (LA) detected. The SLE/LA/HPT association is
      less frequent than the correlated to SLE/LA/anti- beta2Glycoprotein I antibodies
      and was first reported in 1960 by Rapaport et al, in an 11-year- -old girl with
      severe haemorrhagic manifestations.

PMID- 22856395
TI  - Protective effect of Korean red ginseng extract on the infections by H1N1 and
      H3N2 influenza viruses in mice.
AB  - Ginseng has been used in humans for thousands of years and is known to have
      multiple biological and immunomodulatory effects. In this study, we investigated
      whether Korean red ginseng extract would have preventive and antiviral effects on
      influenza virus infection. Oral administration to mice of red ginseng extract
      prior to infection significantly increased survival after infection with the 2009
      pandemic H1N1 virus. Daily oral treatment of vaccinated mice with red ginseng
      extract provided enhanced cross-protection against antigenically distinct H1N1
      and H3N2 influenza viruses. Naive mice that were infected with virus mixed with
      red ginseng extract showed significantly enhanced protection, lower levels of
      lung viral titers and interleukin-6, but higher levels of interferon-gamma
      compared with control mice having virus infections without red ginseng extract,
      indicating an antiviral effect of ginseng. In addition, ginseng extract exhibited
      inhibitory effects on the growth of influenza virus in vitro. This study provides
      evidence that intake of ginseng extract will have beneficial effects on
      preventing lethal infection with newly emerging influenza viruses.

PMID- 22856398
TI  - [Streptococcus pyogenes toxic-shock syndrome].
AB  - Recently there has been an exponential increase in invasive infections caused by
      Streptococcus beta hemolyticus group A. In about one third of cases they are
      complicated by toxic shock syndrome, characterized by septic shock and multiorgan
      failure. The authors, by their rarity, report a case of bacteraemia caused by
      Streptococcus pyogenes complicated by toxic shock syndrome.

PMID- 22856399
TI  - [Necrotizing fasciitis post-acute appendicitis].
AB  - Necrotizing fasciitis (FN) is a deep infection of the subcutaneous tissue and
      fascia, resulting in its progressive destruction. Usually it evolves very
      quickly. The authors present a case to FN abdominal wall, an extremely rare
      complication of acute appendicitis. A child had surgical removal of the appendix
      because of gangrenous acute appendicitis, which evolved into severe infection,
      with pain and inflammatory process of the abdominal wall. After diagnosis, he
      underwent a surgical debridement of the abdominal wall and drainage of
      intraperitoneal abscess. Antibiotic therapy, surgical debridement and successive
      dressings were done and at 22nd day a dermo-epidermal graft was done in a small
      residual lesion of the abdominal wall. Because the prognosis is closely related
      to time to correct diagnosis and initiation of appropriate therapy, it's
      extremely important that this diagnosis is considered.

PMID- 22856400
TI  - [Bacterial meningitis. A rare cause].
AB  - BACKGROUND: Meningitis is an uncommon clinical manifestation of invasive
      infection by Streptococcus pyogenes. CASE REPORT: A four years-old female child,
      previously healthy, started a history of high fever, associated to right
      otorrhea, prostration and vomiting. On admission she was haemodynamically stable
      but prostrated, with stiff neck and right otorrhea. Laboratory evaluation showed
      leukocytosis with neutrophilia, thrombocytosis and high C-reactive protein. The
      cerebrospinal fluid (CSF) examination suggested bacterial meningitis and
      treatment with ceftriaxone was started. After Streptococcus pyogenes grew in the
      CSF, clindamycin was added. She completed 15 days of antibiotics and was
      discharged clinically recovered. No neurological or hearing sequelae were
      observed. CONCLUSIONS: Although the incidence of group A streptococcal meningitis
      seems to be low, invasive infection by this agent is raising. Despite the
      excellent evolution of this case, a fatal outcome or neurological sequelae can
      arise, even in healthy children.

PMID- 22856401
TI  - [Acute acalculous cholecystitis in a patient with severe malaria].
AB  - The authors present a clinical case of a 53 years old male admited in an ICU - DI
      (Intensive care Unit of Infectious Disease) with the diagnosis of severe malaria.
      He was treated with IV quinine di-hydrochloride and doxycycline and developed on
      the sixth day an acute alithiasic cholecystitis. Transhepatic percutaneous
      drainage was performed and the patient had good clinical outcome.

PMID- 22856402
TI  - [Ovarian hyperstimulation syndrome in a spontaneous pregnancy].
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is considered to be an
      iatrogenic complication of ovulation induction therapy. However, OHSS may rarely
      be associated with spontaneous ovulatory cycles, usually in multiple or molar
      gestations or hypothyroidism. Clinical manifestations vary and may be potentially
      fatal in severe cases. CASE REPORT: A 28-year-old primigravid, with no history of
      an infertility treatment, presented with enlarged ovaries and ascite. The patient
      had minor abdominal discomfort, without other complains. Ultrasound evaluation
      showed enlarged cystic ovaries and mild ascites. Hormonal profile revealed
      increased estradiol levels, with normal TSH and hCG. The patient was managed
      expectantly with no complications. DISCUSSION: Although spontaneous OHSS is a
      rare entity, it is important to consider it in cases of bilateral ovarian masses
      in pregnancy. Three different mechanisms responsible for the occurrence of
      spontaneous OHSS have been described. This syndrome is thought to be secondary to
      promiscuity of the FSH receptor for hCG and/or TSH. It may occur with normal or
      increased levels of hCG and/or TSH.

PMID- 22856403
TI  - [Eating disorders and type 1 diabetes: about 4 clinical reports].
AB  - Type 1 Diabetes mellitus is a chronic disease, often diagnosed in youth and
      associated with important psychological, familial and social disorders. Its
      intensive treatment with insulin and dietary changes is an extra stress factor in
      a stage of life already complicated. This vulnerability, coupled with low self
      esteem and psychological factors typical of the youth, makes eating disorders
      twice as common in young girls with type 1 diabetes. The omission of insulin is
      the sole purging behavior used to lose weight, culminating in a poor glycemic
      control and increased acute and chronic complications. The treatment seeks to
      achieve specific objectives, depending on the associated psychiatric pathology.
      Because of its frequency, the clinician should be alert to early manifestations
      of this association. We present four clinical cases of young people with type 1
      diabetes and eating disorders, which show the complexity of the approach and
      monitoring of these patients.

PMID- 22856404
TI  - [Negative paraquaturia does not exclude paraquat fatal poisoning].
AB  - The authors present a case report of fatal paraquat poisoning demonstrating
      persistently negative urine paraquat test. A brief review is also made,
      concerning the importance of blood test for paraquat, the false negative results
      in urine test and the need for new effective therapeutic approaches that can
      change the tragic course of most of these poisoning cases.

PMID- 22856405
TI  - [Aggressive NK/T cell leukemia/lymphoma associated with EBV].
AB  - The authors describe an unusual case of a young man presenting with fever,
      asthenia, anorexia and jaundice, associated to hepatosplenomegaly, evolving
      rapidly to multiorganic failure. Final diagnosis revealed an aggressive NK cell
      leukemia/lymphoma associated to the Epstein-Barr virus (EBV). The diagnosis,
      suggested clinically and after bone marrow immunophenotyping, was confirmed by
      morphologic and immunohistochemical findings on the post-mortem hepatic and
      splenic biopsy .The tumor cells were positive for CD3 and cytotoxic molecules,
      TIA, granzyme B and perforin. The herein reported case is a rare clinical entity,
      only recently recognized and with a difficult early diagnosis. We emphasize the
      necessity to exclude a Natural Killer cell malignancy in cases with identical
      characteristics.

PMID- 22856406
TI  - [Hypertensive crisis in adolescence...what is it?].
AB  - Blood pressure in the pediatric age group is percentilated, depending on age,
      gender and height. Hypertension exists if either systolic or diastolic averages
      are greater than 95th percentile for age, gender and height. The prevalence of
      hypertension in the pediatric age group is about one to three percent, many of
      these patients are mildly affected. The most common cause of hypertension in
      prepubertal child is renal. By adolescence, the hypertension is primary or
      essential in majority of cases. We present a case of hypertension in an
      adolescent of secondary cause.

PMID- 22856407
TI  - [Pure primary breast squamous cell carcinoma].
AB  - Pure and primary breast squamous cell carcinoma is a very rare entity, with a
      prevalence rate of less than 0.1% of all breast carcinomas. Its diagnosis has
      strict histologic and clinical diagnosis criteria, in order to exclude ductal
      breast carcinoma with squamous differentiation, squamous carcinoma originated
      from the breast skin and metastasis from non-mammary tissues. Described as an
      aggressive disease, often treatment-refractory, it has a significantly worse
      prognosis than other nonsquamous cell tumours of the breast. The authors present
      a case report of a woman diagnosed in our institution with breast pure primary
      squamous cell carcinoma and review the literature for diagnosis criteria,
      morphological features, histogenesis, prognosis, and therapy.

PMID- 22856408
TI  - [Pituitary atypical adenoma or malignant corticotrophinoma?].
AB  - Pituitary tumors are classified into typical adenomas, atypical adenomas or
      carcinomas. Carcinoma represents 0.2% of pituitary tumors and is defined by the
      presence of metastases. It often presents as invasive and secreting macroadenoma,
      showing features of malignancy ab initio or over time. The high proliferative
      index (Ki-67) and immunostaining for p53 protein are common indicators of
      aggressiveness. We report a 58 years old male with invasive sellar incidentaloma.
      The hormonal study showed gonadal, thyroid, and somatotrophic failure, with
      increase of corticotropin (ACTH) and cortisol. Transsphenoidal surgery was
      performed and histology revealed a typical corticotrophinoma. The successive
      recurrences over 10 years led to five surgical reoperation and radiotherapy.
      After the third surgery, cellular atypia, Ki-67 of 27% and immunostaining for p53
      were revealed. Subsequently, there were lesions suspicious of metastases (lung
      and lymph nodes), but the biopsy of the lymph nodes was inconclusive. The patient
      died before chemotherapy. In this case, the progressive loss of differentiation
      points to the need for early diagnosis, timely and aggressive treatment.

PMID- 22856409
TI  - [Legionella pneumophila pneumonia and ataxia].
AB  - Legionella pneumophila is responsible for approximately 6-14% of hospital
      admitted community acquired pneumonia (CAP) cases. It is associated with a
      significant severity. In untreated patients is associated with 80% mortality and
      in patients with comorbidities mortality is approximately 100%. The authors
      present a case of Legionella pneumophila pneumonia with cerebellar dysfunction.
      Cerebellar dysfunction is a rare disorder (3.7% of cases), but is well documented
      and has been reported in the first cases of the disease. The authors warn for the
      relevance of the epidemiological context and emphasize the importance of
      reporting cases to identify outbreaks, tracing the source of contamination and
      preventing new cases.

PMID- 22856410
TI  - [Bartter syndrome: a new therapeutic approach].
AB  - The Bartter syndrome is a rare hereditary salt-wasting tubulopathy, characterized
      by metabolic alkalosis, hypokalemia, hyperreninemia and hyperaldosteronemia of
      varying severity. Indomethacin and high doses of oral potassium have been until
      now the therapeutic strategies used, with high risk of gastrointestinal injury.
      Since April 2009, aliskiren--renin inhibitor--has been used in individual cases
      of Bartter syndrome in adults, by ignoring its use in pediatrics. The authors
      present the case of an eight year old child with Bartter syndrome, treated with
      oral potassium chloride and oral indomethacin, whom has been diagnosed a giant
      gastric ulcer. To enable the reduction of the amount of potassium administered,
      we chose to start the aliskiren.

PMID- 22856411
TI  - [Epithelial-myoepithelial carcinoma of parotid gland: a tumor of low grade
      malignancy?].
AB  - Epithelial-myoepithelial carcinoma (EMC) is a rare tumor with predilection for
      the major salivary glands, mainly the parotid gland. It is a tumor of low grade
      malignancy, and despite its tendency to local recurrence with low metastatic
      potential, rare cases of EMC may have an aggressive behavior with distant
      metastasis. Treatment consists primarily of complete surgical resection whenever
      possible followed by radiotherapy (RT) in an attempt to prevent local recurrence.
      The authors describe two cases of patients with EMC from the parotid gland.
      Despite treatment and good local response both later developed pulmonary
      metastases, and also later cerebral metastization. In the sequence of these
      clinical cases, a literature review is made.

PMID- 22856412
TI  - [Histiocytic necrotizing lymphadenitis: (Kukuchi-Fujimoto disease): a diagnostic
      challenge].
AB  - Kikuchi-Fujimoto disease, also called Histiocytic necrotizing lymphadentis, is a
      rare, benign and self-limited disease, with unknown etiology, that affects mainly
      young women, and is characterized by adenopathy (usually localized in the
      cervical region) and fever. Diagnosis is based on histopathological findings in
      ganglionar tissue obtained in excisional biopsy, which allows, in most cases, the
      differential diagnosis with other similar clinical conditions, but which have a
      completely different clinical evolution and therapeutic needs. We report a case
      of a twenty four year old woman with persistent cervical lymphadenopathy, in
      which histopathological examination followed by immunohistochemical analysis of
      ganglionar tissue revealed to be Kikuchi-Fujimoto disease.

PMID- 22856413
TI  - [Biphasic pulmonary blastoma with germ cell differentiation: a challenge in
      diagnosis and treatment].
AB  - Servico de Oncologia Medica. Instituto Portugues de Oncologia Francisco Gentil.
      Porto. Portugal. A 27-year-old man, smoker, presented with three months history
      of fever. A left pulmonary mass inseparable from the heart was identified and
      serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and
      immunohistochemistry of the biopsy specimen, in conjunction with the clinical
      findings were compatible with a diagnosis of pulmonary blastoma with germ cell
      differentiation. The tumour was considered unresectable. The patient was
      submitted to two cycles of primary chemotherapy with bleomycin, etoposide and
      cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not
      regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was
      instituted, but progressive disease was identified after 2 cycles. Six months
      after the diagnosis cerebral metastases were found and the patient died. This
      case illustrates a rare situation of difficult diagnosis and treatment.

PMID- 22856414
TI  - [Malignant peritoneal mesothelioma].
AB  - Malignant peritoneal mesothelioma is a rare tumor arising from the mesothelial
      cells of this serosal membrane. The authors report a case of a female patient
      referred to our hospital for ascites of unknown etiology. As all the exams
      requested were negative, the patient underwent a diagnostic laparoscopy with
      biopsies of multiple peritoneal nodules. Histologic examination confirmed the
      diagnosis of malignant peritoneal mesothelioma. A cytoreductive surgery in
      combination with hyperthermic intraperitoneal chemotherapy was performed. After
      four months of the procedure the patient remains asymptomatic.

PMID- 22856415
TI  - [Nutcracker syndrome. Hematuria without diagnosis?].
AB  - The nutcracker syndrome is associated with left renal vein compression in its
      passage between the abdominal aorta and superior mesenteric artery. This
      phenomenon can cause left renal vein hypertension manifested by abdominal pain,
      hematuria, and pelvic congestion syndrome. The diagnosis is essentially clinical,
      supported by imaging and necessarily one of exclusion. The literature suggests
      that it occurs with a reasonable prevalence in children who present with isolated
      hematuria but is commonly misdiagnosed. We describe two clinical cases of
      children with hematuria whose investigation led to the diagnosis of Nutcracker
      Syndrome. In the presence of hematuria of unknown origin it's necessary to
      consider this entity, highlighting the essential role of a noninvasive test such
      as renal ultrasound with Doppler in its diagnosis.

PMID- 22856416
TI  - [Sarcoidosis in an adolescent].
AB  - Sarcoidosis is a multisystem granulomatous disease. We report the case of 13
      years old boy with mediastinal adenopathies. Etiological investigation revealed
      pulmonary sarcoidosis with periferic adenopathies involvement. Although rare, as
      the differential diagnosis is with multiple pathologies (infectious,tumor,
      rheumatoid), is a disease to be consider.

PMID- 22856417
TI  - [Blueberry muffin baby. A rare presentation of congenital cytomegalovirus
      infection].
AB  - The 'blueberry muffin baby' designation was used to describe the cutaneous
      manifestations of congenital rubella. The differential diagnosis includes other
      TORCH infections, blood dyscrasias, neoplasms, or vascular disorders. We present
      a case of a newborn admitted at birth for presenting disseminated violaceous
      cutaneous nodules. Pregnancy was full term and without infectious complications,
      with prenatal diagnosis of restrictive intrauterine growth, hydramnios and
      suspected esophageal atresia. Maternal serology with no evidence of infection.
      The newborn blood study showed thrombocytopenia, direct hyperbilirubinemia,
      elevated transaminases and coagulopathy. During hospitalization he showed
      progressive hepatosplenomegaly. Skin biopsy showed extramedullary erythropoiesis.
      Myelogram revealed absence of megakaryocytic line precursors. The molecular
      analysis for cytomegalovirus in peripheral blood and bone marrow was positive.
      Cerebral ultrasound examination revealed bilateral calcifications and
      periventricular hyperechogenicity. The placental anatomopathological exam showed
      features suggestive of cytomegalovirus infection. On the fifth day of life was
      initiated ganciclovir. This case presentation is intended to emphasize that
      although it is a rare manifestation, congenital cytomegalovirus infection should
      be considered in the differential diagnosis of 'blueberry muffin baby'.

PMID- 22856418
TI  - [Psoriasis induced by infliximab].
AB  - INTRODUCTION: Recently, the tumor necrosis factor-alpha inhibitors (anti-TNF
      alpha) have been extensively used in clinical practice, in the treatment of
      several immune-mediated disorders, such as inflammatory bowel diseases,
      rheumatoid arthritis and more recently in psoriasis. CASE REPORT: A 35-year-old
      woman, suffering from Crohn's disease, diagnosed in 1994, successfully treated
      with infliximab at the dosage of 5 mg/Kg every 8 weeks, since 10 months ago, was
      referred to our Dermatology Department due to the development of erythematic
      scaling confluent plaques on the scalp, back and umbilical fold. The skin biopsy
      confirmed the clinical diagnosis of psoriasis. Given the severity of the skin
      lesions and its relation with the anti-TNF-alpha, we decided to discontinue
      infliximab. DISCUSSION: Psoriasis results from the combination of polygenic
      predisposition and several triggering factors. Paradoxically, it has been
      described an increase of psoriasis induced by biologic agents. The pathogenic
      mechanism of such paradoxical effect has not yet been clearly elucidated.

PMID- 22856419
TI  - [Langerhans cell histiocytosis and breast].
AB  - Langerhans cell histiocytosis (LCH) is a rare systemic disorder, with a
      diversified presentation and natural history. It can compromise any organ. We
      report a case of a 32-year-old woman who came to our clinic with an asymptomatic
      palpable breast mass. She underwent excisional biopsy. Immunohistochemical and
      pathological evaluation revealed Langerhans cell histiocytosis. No multisystem
      involvement was found.

PMID- 22856420
TI  - [Cryptorchidism in adolescence].
AB  - INTRODUCTION: An early investigation and management op cryptorchidism are
      essential for the diagnosis of associated pathologies, because intra-abdominal
      testis are associated with infertility and neoplasic risk. The authors describe a
      case of late presentation of cryptorchidism associated with genetic disorder.
      CASE REPORT: Adolescent male with 17 years old, referred to Adolescent Clinic for
      short stature and bilateral cryptorchidism. Hypertension, short stature and
      bilateral cryptorchidism were detected in clinical evaluation. Bone age is
      coincident with chronological age and testosterone was slightly below normal
      values. The study of secondary hypertension was negative. He underwent bilateral
      orchidopexy, and histological analysis revealed severe bilateral testicular
      atrophy. The karyotype showed 45,X[15]/46,X,+mar.ish der(Y)(SRY+)[117] mosaicism.
      COMMENTS: With this case report the authors intend to enhance the need of early
      management of cryptorchidism and short stature, in order to improve the
      prognosis.

PMID- 22856421
TI  - [Overlap syndrome].
AB  - The overlap syndromes are characterized by the occurrence in the same patient of
      two or more autoimmune diseases. The overlap syndrome between scleroderma and
      polymyositis is rare. We describe a case of a 58-year-old woman in which the
      clinical expression, the effect of therapy and the evolution, support the concept
      that this syndrome is a distinct clinical entity in the spectrum of autoimmune
      disease.

PMID- 22856422
TI  - [Spontaneous spinal subdural hematoma].
AB  - Spontaneous spinal subdural hematomas are rare and may be caused by vascular
      malformations or bleeding disorders. The diagnosis is based on the conjunction of
      clinical examination with imaging studies, being MRI the gold standard in
      detection and surgical planning. The authors report the case of a patient on
      anticoagulant therapy in the context of atrial fibrillation and mechanical
      prosthetic mitral and tricuspid valves, presenting with sudden onset of dorsal
      pain radiated to both lower limbs, paresthesias and progressive paraparesis. The
      impossibility to perform MRI (because the mechanical valve prostheses) hindered
      the diagnosis of acute spontaneous subdural hematoma. After reversal of the
      anticoagulation and surgical treatment, clinical course was favorable with
      neurological recovery.

PMID- 22856423
TI  - [Levofloxacin hepatotoxicity. Higher risk in diabetics?].
AB  - Levofloxacin, commonly used in medical practice, is prescribed to treat pneumonia
      in patients with comorbidities. Although generally well tolerated and safe, it
      has a well-known, but rarely reported, undercharacterized and ill-identified
      hepatotoxicity, with an unknown signature. With cases of fulminant hepatitis,
      cholestasis episodes reveal an apparently benign progression. Its capability of
      interference with the glucidic metabolism is also well-known, and the
      susceptibility factors to these events include age, presence of multiple
      pathologies and polymedication. The link between Diabetes Mellitus and
      hepatotoxicity has not yet been identified. Nonetheless, reports of several cases
      in literature along with the identification of two cases in insulin-treated
      diabetics, lead to believe that this is a higher-risk group.

PMID- 22856424
TI  - Preclinical evaluation of VB6-845: an anti-EpCAM immunotoxin with reduced
      immunogenic potential.
AB  - VB6-845 is a recombinant immunotoxin comprised of deBouganin (a de-immunized
      plant toxin) genetically linked to an epithelial cell adhesion molecule (EpCAM)
      targeting humanized Fab fragment (4D5MOCB). EpCAM is highly expressed on a wide
      range of epithelial tumors but has limited expression on most normal epithelia
      and therefore represents an excellent target for immunotherapy. A comprehensive
      preclinical evaluation was performed to determine the safety and suitability of
      VB6-845 as a systemically administered drug for the treatment of solid tumors.
      Efficacy studies in mice demonstrated that VB6-845 specifically and potently
      targeted EpCAM-positive tumors. In a dose-ranging study in Sprague-Dawley rats,
      single doses of VB6-845 were well-tolerated resulting in a no-observable adverse
      effect level (NOAEL) of 100 mg/kg whereas repeated doses of VB6-845 resulted in
      vascular leak-associated symptoms particularly at higher dose levels. However,
      much higher doses in Cynomolgus monkeys were well-tolerated when given as a 3
      hour infusion mimicking the intended route of administration in the clinic. In
      addition, VB6-845 proved to be minimally immunogenic in monkeys. The
      toxicological data obtained in Cynomolgus monkeys indicated an excellent safety
      profile with a NOAEL value of 30 mg/kg (equivalent to a 10 mg/kg dose in humans).
      These results are supportive of an exploratory Phase I trial.

PMID- 22856425
TI  - Increased expression of CD133 is a strong predictor of poor outcome in stage I
      colorectal cancer patients.
AB  - OBJECTIVE: Stage I colorectal carcinomas display a highly variable behavior which
      is not accurately predicted by the available prognostic markers. CD133 is
      considered a useful marker to identify the so-called cancer stem cells in
      colorectal cancers (CRCs) and its expression has been shown to have prognostic
      significance in CRC patients. This study aimed to verify whether
      immunohistochemical evaluation of CD133 might correlate with the progression risk
      of stage I CRC patients. MATERIAL AND METHODS: Expression levels of the CD133
      molecule were analyzed and compared in two series of stage I surgically resected
      CRC patients showing disease progression and death for the disease and patients
      with no evidence of disease progression after at least 6 years after surgery.
      RESULTS: A positive staining for CD133 was detected in 52% of the cases with poor
      prognosis and only in 9% of the group with good prognosis, and this difference
      was highly significant (p < 0.001). A significant correlation was detected
      between CD133 expression and histological parameters, such as tumor budding,
      vascular invasion, and presence of lymph node micrometastases but not tumor
      grading, gender, and age. Disease-free survival and cancer-specific survival of
      CD133 negative tumors were significantly longer compared to positive cases. In
      multivariate analyses, CD133 staining confirmed to be a predictor of shorter
      survival independent from vascular invasion but not from lymph nodes
      micrometastases. CONCLUSIONS: These findings demonstrate that CD133
      immunostaining is a useful predictor of high risk progression in stage I CRC
      patients and might help to identify patients eligible for adjuvant chemotherapy.

PMID- 22856426
TI  - Attitude toward money modulates outcome processing: an ERP study.
AB  - Love of money (LOM) is concerned with the attitude toward money, which can be
      measured by the LOM scale through affective, behavioral, and cognitive
      dimensions. Research has observed that monetary attitude was tightly related to
      reward processing and could affect economic behavior. This study examined how
      monetary attitude modulated risky behavior and the underlying neural mechanisms
      of reward processing using event-related potential (ERP) technique. We compared
      both the risk level and brain responses of a high-level LOM (HLOM) group to a low
      level LOM (LLOM) group using a simple gambling task. The behavioral results
      showed that the HLOM group was more risky than the LLOM group, particularly after
      loss. The feedback-related negativity (FRN) was measured as the difference wave
      (gain-related ERP was subtracted from loss-related ERP). The FRN difference wave
      was larger in the HLOM group than that in the LLOM group. The P3 in the HLOM
      group was more positive than that in the LLOM group. These results suggest that
      monetary attitude can modulate both the underlying neural mechanisms and
      behavioral performance in a reward-related task. The HLOM participants are more
      sensitive to gain/loss than the LLOM participants.

PMID- 22856427
TI  - Ciliary epithelium: an underevaluated target for therapeutic regeneration.
AB  - The purpose of stem cells in various organs of vertebrates is to replenish dying
      cells or to replace damaged tissues. However, a few organs have reasonable, while
      others have very limited regenerative, capacity. Until the last two decades, the
      organs such as brain, heart, and kidneys were known to lack regenerative capacity
      for lack of resident stem cell population. However, with advancement of
      techniques and an increase in scientific communication, new discoveries have
      brought novel concepts and data to discover and manipulate these valuable
      resources. Much focus has been devoted to understanding the regulation and
      maintenance of these stem cells. We discuss the preclinical data emerging from
      retino-vascular interactions useful in the exploitation of ciliary epithelium
      derived stem cells for therapeutic regeneration.

PMID- 22856428
TI  - Paracrine sonic hedgehog signaling derived from tumor epithelial cells: a key
      regulator in the pancreatic tumor microenvironment.
AB  - Activation of the hedgehog (Hh) signaling pathway is involved in embryo
      development and tumorigenesis. While normal pancreatic tissue exhibits little Hh
      pathway activity, patients with pancreatic adenocarcinoma have high levels of Hh
      pathway signaling in both the tumor epithelia and the surrounding stromal tissue.
      Hh ligands expressed by pancreatic cancers promote tumor growth indirectly by
      activating Hh signaling in the surrounding stroma. This paracrine activation of
      Hh signaling in the tumor microenvironment provides a more favorable environment
      for tumor cellular proliferation, metastasis, and resistance to therapy. Taken
      together, these findings are of valuable implications for the use of Hh pathway
      inhibitors currently in development and inhibition of the Hh pathway paracrine
      loop in pancreatic cancer.

PMID- 22856429
TI  - Thymosin beta4: a potential molecular target for tumor therapy.
AB  - Thymosin beta4 (Tbeta4), a 5 kDa protein, has been demonstrated to play an
      important role in a variety of biological activities, such as actin sequestering,
      cellular motility, migration, inflammation, and damage repair. Recently, several
      novel findings provided compelling evidence that Tbeta4 played a key role in
      facilitating tumor metastasis and angiogenesis. It has been found that Tbeta4
      expressed increasingly in a number of metastatic tumors, which was associated
      with an increased expression of a known angiogenic factor, vascular endothelial
      growth factor. Thus, Tbeta4 provided a potential target of opportunity for cancer
      management, especially for cancer metastasis therapy.

PMID- 22856432
TI  - The effects of nrf2 on tumor angiogenesis: a review of the possible mechanisms of
      action.
AB  - To date, preclinical and clinical data have shown that various cancer patients
      benefit from antiangiogenic therapy because of the important role of angiogenesis
      in the tumor development process. NF-E2-related factor 2 (Nrf2) is recognized as
      a key transcription factor of genes coding for various antioxidant and
      cytoprotective enzymes, and Nrf2 plays important roles during tumor progression.
      Recent studies have begun to explore the role of Nrf2 in tumor angiogenesis,
      which may be to promote the advancement of tumor antiangiogenic therapy. This
      article reviews the Nrf2-related pathways involved in tumor angiogenesis and
      summarizes the possible mechanisms of Nrf2 action as a pro-angiogenic factor in
      tumor progression.

PMID- 22856430
TI  - Targeting the regulatory machinery of BIM for cancer therapy.
AB  - BIM represents a BH3-only proapoptotic member of the BCL-2 family of apoptotic
      regulatory proteins. Recent evidence suggests that in addition to its involvement
      in normal homeostasis, BIM plays a critical role in tumor cell biology, including
      the regulation of tumorigenesis through activities as a tumor suppressor, tumor
      metastasis, and tumor cell survival. Consequently, BIM has become the focus of
      intense interest as a potential target for cancer chemotherapy. The control of
      BIM expression is complex, and involves multiple factors, including epigenetic
      events (i.e., promoter acetylation or methylation, miRNA), transcription factors,
      posttranscriptional regulation, and posttranslational modifications, most notably
      phosphorylation. Significantly, the expression of BIM by tumor cells has been
      shown to play an important role in determining the response of transformed cells
      to not only conventional cytotoxic agents, but also to a broad array of targeted
      agents that interrupt cell signaling and survival pathways. Furthermore,
      modifications in BIM expression may be exploited to improve the therapeutic
      activity and potentially the selectivity of such agents. It is likely that
      evolving insights into the factors that regulate BIM expression will ultimately
      lead to novel BIM-based therapeutic strategies in the future.

PMID- 22856433
TI  - PAX proteins and fables of their reconstruction.
AB  - The PAX proteins derive their name from the "paired box," a region of homology
      first described between the Drosophila paired (Prd) and gooseberry (Gsb) proteins
      and later found to encode a sequence-specific DNA-binding activity. Both Prd and
      Gsb also contain a homeodomain, and this combination of DNA-binding domains is
      conserved in ancestral predecessors, reflecting an early "homeodomain-capturing"
      event. In addition, the prototypic PAX protein was thought to contain 2
      additional features, namely the octapeptide (or eh1) motif and PHT (or OAR)
      domain-both modulate PAX regulatory activity but are not unique to the PAX
      family. Together with gene duplications and mutagenesis, a domain loss model
      accounts for the distinct architecture and sequence of extant PAX proteins.
      Despite the disparate evolutionary history of these 4 conserved motifs, there is
      a remarkable level of interplay that is modulated by discrete sequences elsewhere
      in the protein. Here, the implications with respect to the evolution of PAX
      protein structure and activity are discussed, it is suggested that the sum of
      these constituent domains is more than the contribution of individual parts. When
      combined with alternative splicing and posttranslational modifications, this
      model confers an extraordinary degree of functional diversity to even highly
      related PAX proteins.

PMID- 22856434
TI  - Self-reported oral health needs and dental-care seeking behavior among women who
      use methamphetamine.
AB  - This study describes the prevalence of self-reported oral health needs and dental
      care-seeking behavior among women who use methamphetamine, using respondent
      driven sampling in San Francisco, California, from 2007 to 2009 (N = 322). The
      sample had a high prevalence of self-reported dental needs; however, a low
      proportion of those reporting needs sought care. In bivariate analysis, the
      preferred route of methamphetamine use and frequency were not associated with
      self-reported dental needs. Over 90% of the sample used illicit substances in
      addition to methamphetamine, which may limit our ability to detect an association
      between methamphetamine use and oral health needs.

PMID- 22856431
TI  - Prostate cancer and parasitism of the bone hematopoietic stem cell niche.
AB  - A subpopulation of men that appear cured of prostate cancer (PCa) develop bone
      metastases many years after prostatectomy. This observation indicates that PCa
      cells were present outside of the prostate at the time of prostatectomy and
      remained dormant. Several lines of evidence indicate that there are disseminated
      tumor cells (DTCs) in the bone marrow at the time of prostatectomy. DTCs
      parasitize the bone microenvironment, where they derive support and impact the
      microenvironment itself. These DTCs appear to be a heterogeneous population of
      PCa cells; however, some of them appear to have some aspects of a cancer stem
      cell (CSC) phenotype as they can develop into clinically detectable metastases.
      The concept of CSC is controversial; however, several markers of CSC have been
      identified for PCa, which may represent cells of either basal or luminal origin.
      These DTCs have now been shown to compete for the hematopoietic stem cell niche
      in bone, where they may be placed in a dormant state. Interaction with a variety
      of host factors, including cytokine and cells, may impact the metastatic
      development and progression, including the dormant state. For example, myeloid
      cells have been shown to impact both the premetastatic niche and established
      tumors. Understanding the concepts of how PCa successfully parasitizes the bone
      microenvironment is paramount toward identifying therapeutic candidates to
      prevent or diminish PCa bone metastases.

PMID- 22856435
TI  - A qualitative exploration of individuals' motivators for seeking substance user
      treatment.
AB  - Substance abuse continues to greatly impact the US population. The purpose of
      this study is to improve understanding of the reasons why individuals seek
      substance user treatment. Qualitative interviews were conducted with 50 men (n =
      25) and women (n = 25) across eight substance user treatment programs in Durham,
      North Carolina, in 2010. We identify six motivating themes regarding reasons for
      seeking treatment and explore how these themes vary by the participants' mode of
      entry into treatment. Findings provide a holistic understanding of how and why
      individuals come into treatment that can enhance the quality and impact of
      substance user services.

PMID- 22856436
TI  - Percutaneous transhepatic self-expanding metal stents for palliation of malignant
      biliary obstruction.
AB  - BACKGROUND: Malignant biliary obstruction is often inoperable at presentation and
      has a poor prognosis. Percutaneously placed self-expanding metal stents (SEMS)
      have been widely used for palliation of malignant biliary obstruction as an
      alternative to major bypass surgery or when endoscopic drainage is not
      technically feasible. The success rate, procedural complications and outcomes in
      patients who underwent placement of SEMS in a tertiary referral centre are
      presented. METHODS: All patients who had percutaneous transhepatic
      cholangiography (PTC) and SEMS for palliation of malignant biliary obstruction
      between May 2008 and July 2010 at Groote Schuur Hospital, Cape Town, were
      reviewed. A retrospective chart review was undertaken using multidisciplinary
      case notes of all patients. The data analysed included demographic information,
      diagnosis, level of biliary obstruction, number and type of procedures, efficacy
      and complications of SEMS insertion. Boston Scientific 69 mm by 10 mm Wallstent
      SEMS were used in all patients. RESULTS; Fifty patients (28 men, 22 women, mean
      age 61 years, range 48 - 80 years) underwent percutaneous SEMS placement. Twenty
      one patients had biliary obstruction at the level of the hilum involving the
      hepatic duct bifurcation, 5 in the mid-common bile duct and 24 in the low common
      bile duct. In 20 patients (40%) SEMS were placed at the time of initial biliary
      drainage (one-stage procedure), while the remaining 30 patients underwent stent
      placement within 2 - 23 days of biliary drainage as a two-stage procedure because
      of difficult access through the lesion during the initial procedure. Five
      patients (10%) required bilateral SEMS insertion. Stent placement was successful
      in all patients and biliary obstruction was relieved in all. The mean serum
      bilirubin level decreased by a mean of 56% from 294 umol/l to 129 umol/l measured
      5 days after stent insertion. Mean hospital stay after stent insertion was 4.1
      days. The average length of hospital stay for patients who underwent a one-stage
      procedure was 3.2 days (range 1 - 11 days), and for patients who underwent a two
      stage procedure 7.6 days (range 3 - 23 days). Nine patients (18%) developed a
      procedure-related complication, which included cholangitis after stent insertion
      (n=4), cholangitic liver abscesses (n=1), subphrenic liver collection (n=1), bile
      leakage (n=1) and cholecystitis (n=2). Three patients (6%) developed
      complications unrelated to SEMS insertion, which included myocardial ischaemia
      (n=2) and pneumonia (n=1). Stent occlusion occurred in 4 patients (8%) within a
      week as result of stent migration (n=3) or presumed biliary sludge (n=1); 2 (4%)
      stents occluded between 7 days and 1 month. Four patients (8%) died during
      hospital admission due to pre-existing biliary sepsis (n=3) and pneumonia (n=1).
      Nine patients developed duodenal obstruction due to disease progression and
      required endoscopic duodenal stenting. Four patients (8%) survived less than 1
      month, 12 (24%) between 1 month and 3 months, 11 (22%) between 3 and 6 months,
      and 10 (20%) beyond 6 months. Follow-up was not possible for 9 patients (18%)
      from distant referral sites. CONCLUSION: These results demonstrate that
      percutaneously placed SEMS achieved satisfactory palliation with a low
      complication rate in a high-risk patient group with advanced malignant biliary
      obstruction.

PMID- 22856437
TI  - Laparoscopic cholecystectomy in acute cholecystitis: an analysis of the risk
      factors.
AB  - BACKGROUND AND AIM: Laparoscopic cholecystectomy (LC) is increasingly being used
      as the initial surgical approach in patients with acute cholecystitis (AC). We
      describe our experience with LC in the treatment of AC. MATERIALS AND METHODS: In
      this study 2 412 patients underwent LC, in 315 cases for AC. The diagnosis was
      based on clinical, laboratory and intra-operative findings. Rates of conversion,
      complications, length of hospital stay, operating times, and factors associated
      with conversion or morbidity were analysed. RESULTS: Conversion to open
      cholecystectomy was necessary in 60 patients (19.04%) with AC. Factors associated
      with conversion were age >65 years, male gender, presence of empyema, previous
      abdominal surgery, and fever (temperature >37.5oC). There were no deaths, and the
      complication rate was 6.4%. The only risk factor for morbidity was a bilirubin
      level of >20.52 umol/l. The operating time and hospital stay were significantly
      longer in AC than in elective cases. CONCLUSIONS: LC for AC is technically
      demanding but safe and effective. With patience, experience, careful dissection
      and identification of vital structures, the laparoscopic approach is safe in the
      majority of cases.

PMID- 22856438
TI  - Oesophageal pouches and diverticula: a pictorial review.
AB  - Diverticula of the oesophagus are rare. They can occur at any level, and are
      often defined by their anatomical location. Three categories are recognised,
      namely pharyngo-oesophageal, parabronchial and epiphrenic. Although these
      diverticula are often asymptomatic, patients can develop significant problems
      with dysphagia, regurgitation and aspiration. The causation of oesophageal
      diverticula is controversial; however, the popular current belief is that most
      occur because of oesophageal dysmotility. This paper demonstrates the categories
      of oesophageal diverticula pictorially, including the radiological features and
      underlying pathology.

PMID- 22856440
TI  - Single-centre comparison of a novel single-step balloon inflation device and
      Amplatz sheath dilatation during percutaneous nephrolithotomy: a pilot study.
AB  - OBJECTIVE: A new second-generation balloon dilatation device for percutaneous
      nephrolithotomy (PCNL) has been launched, promising to challenge the traditional
      Amplatz serial dilators (ASDs). This device allows for the polyurethane sheath to
      be deployed on balloon inflation. Our primary objective in this pilot study was
      to determine whether the use of this new device impacted on overall patient
      outcome when compared with the traditional ASD system. DESIGN: Retrospective
      chart review. SETTING: Department of Urology, Inkosi Albert Luthuli Central
      Hospital, Durban. Subject. Single-centre comparison of a novel single-step
      balloon inflation device and Amplatz sheath dilatation during percutaneous
      nephrolithotomy - a pilot study. Outcome measures. Single procedure success
      rates, retreatment rates, hospital stay, haemoglobin concentration, calculi
      volume, calculi configuration, patient demographics. RESULTS: The stone-free
      rates after a single procedure were 30% (3/10) in the Amplatz sheath dilatation
      arm (series 1) and 80% (8/10) in the single-step balloon inflation device arm
      (series 2). Correspondingly, 11 individual repeat procedures in 7 patients (4
      relook PCNLs, 5 ureteroscopies and 2 extracorporeal shockwave lithotripsies) were
      required in series 1 to render the remaining 70% stone free. Mean hospital stay
      was 5.2 days (range 3 - 10 days) in series 1 and 3.8 days in series 2. The mean
      fall in haemoglobin concentration after treatment was 1.79 g/dl in the whole
      group, 2.1 g/dl in series 1, and 1.5 g/dl in series 2. CONCLUSION: The single
      step balloon dilatation device is found to have an improved patient outcome
      compared with ASDs.

PMID- 22856439
TI  - The histology of peau d'orange in breast cancer -  what are the implications for
      surgery?
AB  - INTRODUCTION: Surgery is sometimes performed on patients with peau d'orange
      (dermal oedema) of the breast. This may be done to achieve local control of
      cancer after neo-adjuvant chemotherapy or in resectable locally advanced disease.
      Conventional practice is not to place excision lines through areas of peau
      d'orange for fear of recurrence in such an area. The question can be asked
      whether this wisdom is still valid in modern practice. No formal cohort studies
      documenting the histopathology of the skin in areas of peau d'orange have been
      published, and available descriptions are scanty. AIM: To describe the
      histopathological features of peau d'orange. METHOD: Consecutive patients
      undergoing mastectomy for cancer in whom peau d'orange was present were selected
      over a period of 2 years. Blocks of skin were excised from areas of peau d'orange
      and examined histologically. The presence, nature and location of malignant cells
      were recorded and correlated with lymph node pathology. Prior administration of
      neo-adjuvant chemotherapy was noted. RESULTS: Twenty-six mastectomy specimens
      were examined. Tumour islands in lymphatics were identified in 10 of the 26
      specimens. These tumour groups were found in lymph vessels of both the
      superficial and deep dermal plexuses. In 1 specimen the presence of malignant
      cells was equivocal. Metastatic tumour was present in axillary lymph nodes in 19
      of 22 specimens. Fourteen patients had been treated with neo-adjuvant
      chemotherapy, and 5 of their specimens exhibited the presence of tumour cell
      groups in lymphovascular channels. CONCLUSION: Tumour cells were present in the
      lymphatic vessels in areas of peau d'orange in 38% of the specimens studied. It
      would be expected that placing an excision line in such an area would result in
      an incomplete cancer operation in a high percentage of, but not all, cases.

PMID- 22856441
TI  - Treatment of male urethral strictures - possible reasons for the use of repeated
      dilatation or internal urethrotomy rather than urethroplasty.
AB  - OBJECTIVE: To investigate the possible reasons for repeated urethral dilatation
      or optical internal urethrotomy rather than urethroplasty in the treatment of
      male urethral strictures. PATIENTS AND METHODS: Men referred to the stricture
      clinic of our institution during the period April 2007 - March 2008 were reviewed
      and the operative urological procedures performed in the same period were
      analysed. Statistical analysis was performed using Student's t-test and Fisher's
      exact test (p<0.05 statistically significant). RESULTS: The mean age of the 125
      men was 49.9 years (range 12.8 - 93.4 years). Previous stricture treatment had
      been given 1 - 2, 3 - 4 and 5 - 6 times in 52%, 32% and 12% of patients,
      respectively (4% had not undergone treatment). In these groups, previous
      treatment was dilatation in 70%, 76% and 72%, urethrotomy in 26%, 15% and 28%,
      and urethroplasty in 4%, 9% and 0, respectively. The group with 5 - 6 compared
      with 1 - 2 previous treatments was significantly older (mean age 60.2 v. 46.6
      years) and had a significantly greater proportion with underlying co-morbidities
      (80% v. 52%). The group that had undergone urethroplasty compared with 5 - 6
      repeated dilatations or urethrotomies was significantly younger (mean age 48.2 v.
      60.2 years) with a lower prevalence of co-morbidities (47% v. 80%). During the
      study period urethroplasty was performed in 16 (2%) of 821 inpatients, whereas 55
      men were seen who had undergone >=3 previous procedures, indicating that
      urethroplasty was performed in less than one-third of cases in which it would
      have been the optimal treatment. Owing to limited theatre time, procedures
      indicated for malignancy, urolithiasis, renal failure and congenital anomalies
      were performed more often than urethroplasty. CONCLUSIONS: Factors that possibly
      influenced the decision to perform repeated urethrotomy or dilatation instead of
      urethroplasty were limited theatre time, increased patient age and the presence
      of underlying co-morbidities.

PMID- 22856442
TI  - Beware the left-sided gallbladder.
AB  - A left-sided gallbladder is a rare biliary anomaly with a prevalence of 0.2%. Its
      identification is important because of the numerous and potentially hazardous
      associated biliary and vascular anomalies that may be encountered during surgery.

PMID- 22856443
TI  - Diaphragmatic eventration complicated by gastric volvulus with perforation.
AB  - Eventration of the diaphragm with gastric volvulus is uncommon. Gastric
      perforation in these cases is rare and usually associated with acute gastric
      volvulus with strangulation. We describe a case of diaphragmatic eventration with
      chronic gastric volvulus with gastric perforation without strangulation in an
      elderly man.

PMID- 22856444
TI  - Isolated splenic peliosis in an immunocompromised patient.
AB  - BACKGROUND: Peliosis is a rare condition characterised by multiple cyst-like,
      blood-filled cavities within the parenchyma of solid organs, most commonly
      affecting the liver. Isolated splenic peliosis is an even more unusual
      phenomenon. Patients with AIDS may develop peliosis in association with bacillary
      angiomatosis. This is due to secondary infection with Bartonella henselae or a
      similar organism, Rochalimaea henselae. CASE PRESENTATION: A 45-year-old HIV
      positive man on antiretroviral therapy presented with a left hypochodrial
      abdominal mass. Radiological and histopathological examination confirmed splenic
      peliosis.

PMID- 22856445
TI  - Misdiagnosis of diaphragmatic rupture in a  trauma setting.
AB  - Distinguishing diaphragmatic eventration from rupture in the trauma setting can
      be a considerable challenge. We present a case involving a man suffering from
      chest pain and with a raised left hemidiaphragm on the chest radiograph after a
      motor vehicle injury. A review of the literature discusses the use of imaging
      modalities and subsequent surgical diagnostic procedures in the face of
      uncertainty.

PMID- 22856446
TI  - AAST grade III pancreatic injury following blunt abdominal trauma.
AB  - Isolated pancreatic trauma with major pancreatic duct disruption is a rare
      finding; it can present with equivocal clinical signs. Serum amylase levels and
      diagnostic contrast-enhanced computed tomography can facilitate the diagnostic
      process.

PMID- 22856447
TI  - Bilateral synchronous testicular germ cell tumours in a patient with bilateral
      cryptorchidism.
AB  - Bilateral testicular tumours are rare, and 80% of bilateral tumours are
      metachronous. The incidence of testicular tumours is high in cryptorchidism.
      Synchronous bilateral testicular tumours are rare, and bilateral synchronous
      testicular tumours in bilateral cryptorchidism extremely rare, probably not
      reported previously.

PMID- 22856448
TI  - Unexpected intra-operative diagnosis of a large cystic phaeochromocytoma and
      secondary nifedipine pharmacobezoar.
AB  - Cystic phaeochromocytoma is a rare neuro-endocrine tumour that is frequently
      asymptomatic and often diagnosed incidentally on imaging or intra-operatively. A
      pharmacobezoar is a rare complication of extended-release drug delivery systems.
      We present a case of a 70-year-old woman diagnosed intra-operatively with cystic
      phaeochromocytoma and antihypertensive pharmacobezoar.

PMID- 22856450
TI  - Intestinal prolapse through a persistent omphalomesenteric duct causing small
      bowel obstruction.
AB  - Persistent omphalomesenteric duct as a cause of small-bowel obstruction is an
      exceptional finding. A neonate presented with occlusion due to intestinal
      prolapse through a persistent omphalomesenteric duct. Remnants of the duct were
      successfully resected, and the postoperative course was uneventful. We discuss
      the presentation of omphalomesenteric duct and its management.

PMID- 22856449
TI  - Enterovesical fistula in an HIV patient - reactivation of tuberculosis as part of
      IRIS.
AB  - Enterovesical fistula is a known complication of tuberculosis (TB) of the
      abdomen. We present a case of a young HIV-infected man who developed an
      enterovesical fistula due to reactivation of TB as part of the immune
      reconstitution inflammatory syndrome (IRIS).

PMID- 22856451
TI  - A 'wandering' gallstone.
AB  - When all three of the features of Rigler's triad are present on an abdominal
      radiograph, the cause of a small-bowel obstruction can be identified.

PMID- 22856452
TI  - Effect of thermal processing on free and total phenolics in nine varieties of
      common beans.
AB  - Though much attention has been devoted to phenolics in beans, to our knowledge no
      studies have been done to determine the effect commercial canning has on these
      compounds. Free and total phenolic concentration in 18 cultivars of raw beans and
      9 cultivars of commercial canned beans was determined. Alkaline hydrolysis was
      used on samples prior to analysis by Folin-Ciocalteu's reagent (FCR) and ferric
      reducing antioxidant power (FRAP). A correction for non-phenolic antioxidants,
      interferences, was then made. There is a significant difference between the free
      phenolics of canned and raw beans using FCR (P = 0.006) but not FRAP. There is
      also a significant difference in the total phenolics of canned and raw beans
      using FRAP (P = 0.006) but not FCR. When considered on a single serving basis,
      the amount of phenolics in canned beans is comparable to that provided by raw
      fruits and vegetables.

PMID- 22856453
TI  - Anti-atherogenic effects of a phenol-rich fraction from Brazilian red wine (Vitis
      labrusca L.) in hypercholesterolemic low-density lipoprotein receptor knockout
      mice.
AB  - Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a
      reduced risk of morbidity and mortality from cardiovascular disease. The aim of
      this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic
      ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis
      labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL)
      receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic
      diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end
      of the treatment, the level of plasma lipids, the vascular reactivity, and the
      atherosclerotic lesions were evaluated. Our results demonstrated that the
      treatment with EAF at 3 mg/kg significantly decreased total cholesterol,
      triglycerides, and LDL plus very low-density lipoprotein levels compared with
      control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also
      preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta
      from hypercholesterolemic LDLr-/- mice. This result is in agreement with the
      degree of lipid deposit on arteries. Taken together, the results show for the
      first time that the lowest concentration of an EAF obtained from a red wine
      produced in southern Brazil significantly reduced the progression of
      atherosclerosis in mice.

PMID- 22856454
TI  - Affective startle potentiation in juvenile offenders: the role of conduct
      problems and psychopathic traits.
AB  - Emotion processing difficulties are observed in antisocial individuals exhibiting
      serious antisocial behavior. This study examined emotion processing in 40 male
      juvenile offenders (JOs) and 52 male controls by measuring startle reflex
      responses to aversive sounds during the passive viewing of affective and neutral
      images. JOs as a group exhibited reduced startle-elicited blinks across all slide
      categories compared to normal controls. Moreover, within the offender group those
      with more conduct disorder symptoms and higher levels of psychopathic traits
      displayed reduced startle amplitudes compared to lower-scoring offenders. The
      finding that startle magnitudes were inversely related to severity of conduct
      problems supports a dimensional or continuous approach to understanding
      externalizing disorders. Reductions in amygdala activity could lead to blunted
      startle magnitudes. The current findings not only provide further evidence that
      antisocial children have a general defensive motivational system dysfunction and
      present with impairments in neural systems that subserve emotion processing, but
      also show for the first time that those with more severe conduct problems have
      reduced startle responses compared to those who are less severely affected. The
      implications of these findings for interventions with JOs are discussed.

PMID- 22856455
TI  - Data mining of protein-binding profiling data identifies structural modifications
      that distinguish selective and promiscuous compounds.
AB  - Activity profiling of compound collections across multiple targets is
      increasingly being used in probe and drug discovery. Herein, we discuss an
      approach to systematically analyzing the structure-activity relationships of a
      large screening profile data with emphasis on identifying structural changes that
      have a significant impact on the number of proteins to which a compound binds. As
      a case study, we analyzed a recently released public data set of more than 15 000
      compounds screened across 100 sequence-unrelated proteins. The screened compounds
      have different origins and include natural products, synthetic molecules from
      academic groups, and commercial compounds. Similar synthetic structures from
      academic groups showed, overall, greater promiscuity differences than do natural
      products and commercial compounds. The method implemented in this work readily
      identified structural changes that differentiated highly specific from
      promiscuous compounds. This approach is general and can be applied to analyze any
      other large-scale protein-binding profile data.

PMID- 22856457
TI  - Emission switching of 4,6-diphenylpyrimidones: solvent and solid state effects.
AB  - The photophysics of 1-ethyl-4,6-bis(4-methoxyphenyl)-2(1H)-pyrimidone (1) and 1
      ethyl-4,6-bis(4-(dimethylamino)phenyl)-2(1H)-pyrimidone (2) were investigated to
      determine the mechanisms of emission switching in response to protonation. UV-vis
      and steady state emission spectroscopy of the protonated and unprotonated forms
      across a range of solvents reveal the polarity dependence of the vertical
      excitation energies. Emission lifetimes and quantum yields show the solvent
      dependency of the excited states. Emission enhancements were observed in
      polyethylene glycol solutions and in the solid state (both thin film and single
      crystal), demonstrating the role of intramolecular rotation in thermal relaxation
      of the excited states. TD-DFT calculations provide insights into the excited
      state geometries and the role of intramolecular charge transfer. The collected
      data show that emission of diphenylpyrimidones can be modulated by four factors,
      including the identity of the electron-donating auxochrome, protonation state,
      solvent polarity, and viscosity.

PMID- 22856458
TI  - CcpA-mediated enhancement of sugar and amino acid metabolism in Lysinibacillus
      sphaericus by NMR-based metabolomics.
AB  - Lysinibacillus sphaericus is a bacterium incapable of metabolizing sugars with
      the sole exception of N-acetylglucosamine. To unravel the regulatory role of
      catabolite control protein A (CcpA) in the sugar metabolism of L. sphaericus, a
      ccpA deficient mutant was constructed by homologous recombination. The mutant
      showed growth deficiency and a low efficiency of carbon and energy utilization.
      NMR spectroscopy in combination with multivariate data analysis revealed that the
      metabolome of L. sphaericus was dominated by 25 metabolites mainly including
      amino acids, carbohydrate derivatives and organic acids, and that the mutation of
      the ccpA gene caused significant reduction of leucine, valine, alanine,
      threonine, glutamate, lysine, d-ornithine, tyrosine, uridine 5'-diphospho-N
      acetlyglucosamine formate, fumarate, phenylalanine, aspartate, asparagine, and
      acetate but elevation of ribose-5-phosphate, and uracil. Furthermore, the
      networks of CcpA-mediated regulation based on the metabolome were constructed by
      arrangement of significantly decreasing or increasing metabolites. The network
      map suggests CcpA regulates and promotes sugar and amino acid metabolism of L.
      sphaericus.

PMID- 22856456
TI  - Marine algal toxin azaspiracid is an open-state blocker of hERG potassium
      channels.
AB  - Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in
      shellfish and represent an emerging human health risk. Although human exposure is
      primarily manifested by severe and protracted diarrhea, this toxin class has been
      shown to be highly cytotoxic, a teratogen to developing fish, and a possible
      carcinogen in mice. Until now, AZA's molecular target has not yet been
      determined. Using three independent methods (voltage clamp, channel binding
      assay, and thallium flux assay), we have for the first time demonstrated that
      AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-a-go-go related
      gene) potassium channel heterologously expressed in HEK-293 mammalian cells.
      Inhibition of K(+) current for each AZA analogue was concentration-dependent
      (IC(50) value range: 0.64-0.84 MUM). The mechanism of hERG channel inhibition by
      AZA1 was investigated further in Xenopus oocytes where it was shown to be an open
      state-dependent blocker and, using mutant channels, to interact with F656 but not
      with Y652 within the S6 transmembrane domain that forms the channel's central
      pore. AZA1, AZA2, and AZA3 were each shown to inhibit [(3)H]dofetilide binding to
      the hERG channel and thallium ion flux through the channel (IC(50) value range:
      2.1-6.6 MUM). AZA1 did not block the K(+) current of the closely related EAG1
      channel. Collectively, these data suggest that the AZAs physically block the K(+)
      conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the
      open pore. Although the concentrations necessary to block hERG channels are
      relatively high, AZA-induced blockage may prove to contribute to the
      toxicological properties of the AZAs.

PMID- 22856459
TI  - Predictors of primary care referrals to a vascular disease prevention lifestyle
      program among participants in a cluster randomised trial.
AB  - BACKGROUND: Cardiovascular disease accounts for a large burden of disease, but is
      amenable to prevention through lifestyle modification. This paper examines
      patient and practice predictors of referral to a lifestyle modification program
      (LMP) offered as part of a cluster randomised controlled trial (RCT) of
      prevention of vascular disease in primary care. METHODS: Data from the
      intervention arm of a cluster RCT which recruited 36 practices through two rural
      and three urban primary care organisations were used. In each practice, 160
      eligible high risk patients were invited to participate. Practices were randomly
      allocated to intervention or control groups. Intervention practice staff were
      trained in screening, motivational interviewing and counselling and encouraged to
      refer high risk patients to a LMP involving individual and group sessions. Data
      include patient surveys; clinical audit; practice survey on capacity for
      preventive care; referral records from the LMP. Predictors of referral were
      examined using multi-level logistic regression modelling after adjustment for
      confounding factors. RESULTS: Of 301 eligible patients, 190 (63.1%) were referred
      to the LMP. Independent predictors of referral were baseline BMI >= 25 (OR 2.87
      95%CI:1.10, 7.47), physical inactivity (OR 2.90 95%CI:1.36,6.14),
      contemplation/preparation/action stage of change for physical activity (OR 2.75
      95%CI:1.07, 7.03), rural location (OR 12.50 95%CI:1.43, 109.7) and smaller
      practice size (1-3 GPs) (OR 16.05 95%CI:2.74, 94.24). CONCLUSIONS: Providing a
      well-structured evidence-based lifestyle intervention, free of charge to
      patients, with coordination and support for referral processes resulted in over
      60% of participating high risk patients being referred for disease prevention.
      Contrary to expectations, referrals were more frequent from rural and smaller
      practices suggesting that these practices may be more ready to engage with these
      programs. TRIAL REGISTRATION: ACTRN12607000423415.

PMID- 22856461
TI  - Hormonal interactions in the regulation of plant development.
AB  - Plants exhibit a unique developmental flexibility to ever-changing environmental
      conditions. To achieve their profound adaptability, plants are able to maintain
      permanent stem cell populations and form new organs during the entire plant life
      cycle. Signaling substances, called plant hormones, such as auxin, cytokinin,
      abscisic acid, brassinosteroid, ethylene, gibberellin, jasmonic acid, and
      strigolactone, govern and coordinate these developmental processes. Physiological
      and genetic studies have dissected the molecular components of signal perception
      and transduction of the individual hormonal pathways. However, over recent years
      it has become evident that hormones do not act only in a linear pathway. Hormonal
      pathways are interconnected by a complex network of interactions and feedback
      circuits that determines the final outcome of the individual hormone actions.
      This raises questions about the molecular mechanisms underlying hormonal cross
      talk and about how these hormonal networks are established, maintained, and
      modulated throughout plant development.

PMID- 22856460
TI  - Fecundity compensation and tolerance to a sterilizing pathogen in Daphnia.
AB  - Hosts are armed with several lines of defence in the battle against parasites:
      they may prevent the establishment of infection, reduce parasite growth once
      infected or persevere through mechanisms that reduce the damage caused by
      infection, called tolerance. Studies on tolerance in animals have focused on
      mortality, and sterility tolerance has not been investigated experimentally.
      Here, we tested for genetic variation in the multiple steps of defence when the
      invertebrate Daphnia magna is infected with the sterilizing bacterial pathogen
      Pasteuria ramosa: anti-infection resistance, anti-growth resistance and the
      ability to tolerate sterilization once infected. When exposed to nine doses of a
      genetically diverse pathogen inoculum, six host genotypes varied in their average
      susceptibility to infection and in their parasite loads once infected. How host
      fecundity changed with increasing parasite loads did not vary between genotypes,
      indicating that there was no genetic variation for this measure of fecundity
      tolerance. However, genotypes differed in their level of fecundity compensation
      under infection, and we discuss how, by increasing host fitness without targeting
      parasite densities, fecundity compensation is consistent with the functional
      definition of tolerance. Such infection-induced life-history shifts are not
      traditionally considered to be part of the immune response, but may crucially
      reduce harm (in terms of fitness loss) caused by disease, and are a distinct
      source of selection on pathogens.

PMID- 22856462
TI  - Assessing the existing information on the efficacy of bovine vaccination against
      Escherichia coli O157:H7--a systematic review and meta-analysis.
AB  - The objective of this study was to conduct a systematic review and meta-analysis
      to evaluate the existing information on the efficacy of commercial vaccination to
      reduce the prevalence of Escherichia coli O157:H7 in weaned cattle in beef
      feedlot finishing systems under commercial conditions. Currently, only two
      commercial vaccines exist, and thus, only publications reporting the use of
      vaccines targeting type III secreted proteins and/or siderophore receptor and
      porin proteins (SRP) were considered relevant. A total of 18 studies reporting 45
      comparisons were included in this review. Meta-analyses were conducted variously
      on (i) pre-harvest outcomes, (ii) at-harvest outcomes and (iii) both pre-harvest
      and at-harvest outcomes combined. Overall, efficacy of vaccination was
      consistently observed. Efficacy and homogeneity of the results was demonstrated
      for the two-dose regimen, allowing us to conclude with confidence that the two
      dose approach is efficacious. For pre-harvest outcomes and two-dose regimens, the
      odds ratios (OR) were 0.53 (95% CI = 0.45-0.62) for the two vaccines combined and
      0.49 (95% CI = 0.40-0.60) for vaccine targeting type III secreted proteins. The
      test for heterogeneity among studies yielded a Q test P = 0.354 for the two
      vaccines combined and Q test P = 0.269 for the vaccine targeting type III
      secreted proteins, indicating homogeneity in both cases. For pre- and at-harvest
      outcomes combined and two-dose regimens, the odds ratios (OR) were 0.52 (95% CI =
      0.44-0.61) for the two vaccines combined and 0.45 (95% CI = 0.34-0.60) for
      vaccine targeting type III secreted proteins. The test for heterogeneity among
      studies yielded a Q test P = 0.134 for the two vaccines combined indicating
      homogeneity and Q test P = 0.089 for the vaccine targeting type III secreted
      proteins indicating heterogeneity. Based on this meta-analysis, bovine
      vaccination appears to be an effective approach to the pre-harvest control of E.
      coli O157:H7.

PMID- 22856463
TI  - Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus
      infections in allogeneic hematopoietic stem cell transplantation for
      hematological malignancies.
AB  - BACKGROUND: Intensified conditioning regimens (increasing the intensity of
      standard myeloablative conditioning) for hematological malignancies in allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) could reduce the relapse rate
      of the underlying disease, but it might simultaneously increase the transplant
      related mortality including the mortality of infections. To explore whether
      intensified conditioning affected Epstein-Barr virus (EBV) and cytomegalovirus
      (CMV) infections, 185 patients undergoing allo-HSCT were enrolled. METHODS: A
      total of 104 cases received standard and 81 intensified conditioning.
      Cyclosporine A (CsA) withdrawal and/or donor lymphocyte infusion (DLI) were
      conducted in high-risk patients. The EBV-DNA and CMV-DNA levels of blood were
      monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR)
      and immune reconstitution of recipients were analyzed by flow cytometry. RESULTS:
      The 3-year cumulative incidence of EBV viremia, EBV-associated diseases and
      mortality of EBV-associated diseases were 25.3% +/- 4.6%, 10.5% +/- 3.4% and 0.0%
      +/- 0.0% in the standard group, compared with 45.6% +/- 6.5%, 26.0% +/-5.3% and
      7.3% +/- 3.1% in the intensified group (P = 0.002, P = 0.002, P = 0.008). The 3
      year cumulative incidence of CMV viremia and CMV-associated diseases, mortality
      of CMV-associated diseases and incidence of bacterial and fungal infections were
      similar between the two groups (P = 0.855, P = 0.581, P = 0.933, P = 0.142, P =
      0.182, respectively). Multivariate analysis showed that intensified conditioning
      was one of the risk factors for EBV viremia and EBV-associated diseases (P =
      0.037, P = 0.037), but it had no effects on CMV infections. The percentage of
      CD4+ T cells and CD4+/CD8+ ratio at 3 months post-transplantation were lower in
      the intensified group (P = 0.032, P = 0.022). The 3-year OS and DFS in the
      standard group were 62.2% +/- 5.8% and 60.6% +/- 5.6%, compared with 51.6% +/-
      6.2% and 51.1% +/- 5.9% in the intensified group (P = 0.029, P = 0.063).
      CONCLUSIONS: Intensified conditioning represents a promising approach for high
      risk hematological malignancies, although it affects early immune reconstitution
      of recipients and increases the incidence and mortality of EBV infections.

PMID- 22856465
TI  - Influence of the ratio of gate length to drain-to-source distance on the electron
      mobility in AlGaN/AlN/GaN heterostructure field-effect transistors.
AB  - Using measured capacitance-voltage curves with different gate lengths and
      current-voltage characteristics at low drain-to-source voltage for the
      AlGaN/AlN/GaN heterostructure field-effect transistors (HFETs) of different drain
      to-source distances, we found that the dominant scattering mechanism in
      AlGaN/AlN/GaN HFETs is determined by the ratio of gate length to drain-to-source
      distance. For devices with small ratio (here, less than 1/2), polarization
      Coulomb field scattering dominates electron mobility. However, for devices with
      large ratio (here, more than 1/2), longitudinal optical (LO) phonon scattering
      and interface roughness scattering are dominant. The reason is closely related to
      polarization Coulomb field scattering.

PMID- 22856466
TI  - Flaxseed does not enhance the estrogenic effect of low-dose estrogen therapy on
      markers of uterine health in ovariectomized rats.
AB  - Flaxseed (FS) is an oilseed rich in phytoestrogens and n-3 polyunsaturated fatty
      acids, compounds that may attenuate bone loss during aging. We previously
      demonstrated using the ovariectomized (OVX) rat model of postmenopausal
      osteoporosis that 10% dietary FS combined with low-dose estrogen therapy (LD)
      preserves vertebral bone mass and strength more so than either treatment alone.
      However, it was prudent to also consider the effect of this intervention on
      uterine tissue as LD, and possibly FS, may have estrogenic, and thus negative,
      effects on uterine tissue. The present study investigated if FS enhances the
      estrogenic effect of LD on markers of uterine health in OVX rats. Three-month-old
      rats were randomized to groups: (1) SHAM, (2) OVX, (3) OVX+FS, (4) OVX+LD, or (5)
      OVX+FS+LD. Ground FS was added to the AIN-93M diet (100 g/kg of diet), and LD was
      delivered by subcutaneous implant (0.42 MUg of 17beta-estradiol/kg of body
      weight/day) to mimic LD in postmenopausal women. After 12 weeks, histological
      analyses of uterine tissue demonstrated flattened or cuboidal luminal epithelia
      organized in a single layer in the OVX group, while FS, LD, and FS+LD induced a
      single layer of elongated luminal epithelia, columnar in shape. The SHAM group
      had the greatest epithelial mass. Cell proliferation was similar among all OVX
      groups. Therefore FS and FS+LD similarly induce estrogen-like effects on the
      morphology of luminal epithelia that are weaker than in the SHAM group without
      inducing cell proliferation in OVX rats. Thus, FS does not enhance the estrogenic
      effect of LD on markers of uterine health in OVX rats.

PMID- 22856467
TI  - Organizational climate and culture.
AB  - Organizational climate and organizational culture theory and research are
      reviewed. The article is first framed with definitions of the constructs, and
      preliminary thoughts on their interrelationships are noted. Organizational
      climate is briefly defined as the meanings people attach to interrelated bundles
      of experiences they have at work. Organizational culture is briefly defined as
      the basic assumptions about the world and the values that guide life in
      organizations. A brief history of climate research is presented, followed by the
      major accomplishments in research on the topic with regard to levels issues, the
      foci of climate research, and studies of climate strength. A brief overview of
      the more recent study of organizational culture is then introduced, followed by
      samples of important thinking and research on the roles of leadership and
      national culture in understanding organizational culture and performance and
      culture as a moderator variable in research in organizational behavior. The final
      section of the article proposes an integration of climate and culture thinking
      and research and concludes with practical implications for the management of
      effective contemporary organizations. Throughout, recommendations are made for
      additional thinking and research.

PMID- 22856464
TI  - Electrochemically active biofilms: facts and fiction. A review.
AB  - This review examines the electrochemical techniques used to study extracellular
      electron transfer in the electrochemically active biofilms that are used in
      microbial fuel cells and other bioelectrochemical systems. Electrochemically
      active biofilms are defined as biofilms that exchange electrons with conductive
      surfaces: electrodes. Following the electrochemical conventions, and recognizing
      that electrodes can be considered reactants in these bioelectrochemical
      processes, biofilms that deliver electrons to the biofilm electrode are called
      anodic, ie electrode-reducing, biofilms, while biofilms that accept electrons
      from the biofilm electrode are called cathodic, ie electrode-oxidizing, biofilms.
      How to grow these electrochemically active biofilms in bioelectrochemical systems
      is discussed and also the critical choices made in the experimental setup that
      affect the experimental results. The reactor configurations used in
      bioelectrochemical systems research are also described and the authors
      demonstrate how to use selected voltammetric techniques to study extracellular
      electron transfer in bioelectrochemical systems. Finally, some critical concerns
      with the proposed electron transfer mechanisms in bioelectrochemical systems are
      addressed together with the prospects of bioelectrochemical systems as energy
      converting and energy-harvesting devices.

PMID- 22856468
TI  - The BRCA1 S1715N mutation segregates with breast and ovarian cancer in an
      extended family pedigree.

PMID- 22856469
TI  - Comparison of the monocular Humphrey Visual Field and the binocular Humphrey
      Esterman Visual Field test for driver licensing in glaucoma subjects in Sweden.
AB  - BACKGROUND: The purpose of this study was to compare the monocular Humphrey
      Visual Field (HVF) with the binocular Humphrey Esterman Visual Field (HEVF) for
      determining whether subjects suffering from glaucoma fulfilled the new medical
      requirements for possession of a Swedish driver's license. METHODS: HVF SITA Fast
      24-2 full threshold (monocularly) and HEVF (binocularly) were performed
      consecutively on the same day on 40 subjects with glaucomatous damage of varying
      degrees in both eyes. Assessment of results was constituted as either "pass" or
      "fail", according to the new medical requirements put into effect September 1,
      2010 by the Swedish Transport Agency. RESULTS: Forty subjects were recruited and
      participated in the study. Sixteen subjects passed both tests, and sixteen
      subjects failed both tests. Eight subjects passed the HEFV but failed the HVF.
      There was a significant difference between HEVF and HVF (chi(2), p = 0.004).
      There were no subjects who passed the HVF, but failed the HEVF. CONCLUSIONS: The
      monocular visual field test (HVF) gave more specific information about the
      location and depth of the defects, and therefore is the overwhelming method of
      choice for use in diagnostics. The binocular visual field test (HEVF) seems not
      be as efficient as the HVF in finding visual field defects in glaucoma subjects,
      and is therefore doubtful in evaluating visual capabilities in traffic
      situations.

PMID- 22856471
TI  - GA(M)E-QSAR: a novel, fully automatic genetic-algorithm-(meta)-ensembles approach
      for binary classification in ligand-based drug design.
AB  - Computer-aided drug design has become an important component of the drug
      discovery process. Despite the advances in this field, there is not a unique
      modeling approach that can be successfully applied to solve the whole range of
      problems faced during QSAR modeling. Feature selection and ensemble modeling are
      active areas of research in ligand-based drug design. Here we introduce the
      GA(M)E-QSAR algorithm that combines the search and optimization capabilities of
      Genetic Algorithms with the simplicity of the Adaboost ensemble-based
      classification algorithm to solve binary classification problems. We also explore
      the usefulness of Meta-Ensembles trained with Adaboost and Voting schemes to
      further improve the accuracy, generalization, and robustness of the optimal
      Adaboost Single Ensemble derived from the Genetic Algorithm optimization. We
      evaluated the performance of our algorithm using five data sets from the
      literature and found that it is capable of yielding similar or better
      classification results to what has been reported for these data sets with a
      higher enrichment of active compounds relative to the whole actives subset when
      only the most active chemicals are considered. More important, we compared our
      methodology with state of the art feature selection and classification approaches
      and found that it can provide highly accurate, robust, and generalizable models.
      In the case of the Adaboost Ensembles derived from the Genetic Algorithm search,
      the final models are quite simple since they consist of a weighted sum of the
      output of single feature classifiers. Furthermore, the Adaboost scores can be
      used as ranking criterion to prioritize chemicals for synthesis and biological
      evaluation after virtual screening experiments.

PMID- 22856470
TI  - Down-regulation of POLYGALACTURONASE1 alters firmness, tensile strength and water
      loss in apple (Malus x domestica) fruit.
AB  - BACKGROUND: While there is now a significant body of research correlating apple
      (Malus x domestica) fruit softening with the cell wall hydrolase ENDO
      POLYGALACTURONASE1 (PG1), there is currently little knowledge of its
      physiological effects in planta. This study examined the effect of down
      regulation of PG1 expression in 'Royal Gala' apples, a cultivar that typically
      has high levels of PG1, and softens during fruit ripening. RESULTS: PG1
      suppressed 'Royal Gala' apples harvested from multiple seasons were firmer than
      controls after ripening, and intercellular adhesion was higher. Cell wall
      analyses indicated changes in yield and composition of pectin, and a higher
      molecular weight distribution of CDTA-soluble pectin. Structural analyses
      revealed more ruptured cells and free juice in pulled apart sections, suggesting
      improved integrity of intercellular connections and consequent cell rupture due
      to failure of the primary cell walls under stress. PG1-suppressed lines also had
      reduced expansion of cells in the hypodermis of ripe apples, resulting in more
      densely packed cells in this layer. This change in morphology appears to be
      linked with reduced transpirational water loss in the fruit. CONCLUSIONS: These
      findings confirm PG1's role in apple fruit softening and suggests that this is
      achieved in part by reducing cellular adhesion. This is consistent with previous
      studies carried out in strawberry but not with those performed in tomato. In
      apple PG1 also appears to influence other fruit texture characters such as
      juiciness and water loss.

PMID- 22856472
TI  - Building multivariate systems biology models.
AB  - Systems biology methods using large-scale "omics" data sets face unique
      challenges: integrating and analyzing near limitless data space, while
      recognizing and removing systematic variation or noise. Herein we propose a
      complementary multivariate analysis workflow to both integrate "omics" data from
      disparate sources and analyze the results for specific and unique sample
      correlations. This workflow combines principal component analysis (PCA),
      orthogonal projections to latent structures discriminate analysis (OPLS-DA),
      orthogonal 2 projections to latent structures (O2PLS), and shared and unique
      structures (SUS) plots. The workflow is demonstrated using data from a study in
      which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing
      cholesterol levels followed by therapeutic intervention (fenofibrate,
      rosuvastatin, and LXR activator T-0901317). The levels of structural lipids
      (lipidomics) and free fatty acids in liver were quantified via liquid
      chromatography-mass spectrometry (LC-MS). The complementary workflow identified
      diglycerides as key hepatic metabolites affected by dietary cholesterol and drug
      intervention. Modeling of the three therapeutics for mice fed a high-cholesterol
      diet further highlighted diglycerides as metabolites of interest in
      atherogenesis, suggesting a role in eliciting chronic liver inflammation. In
      particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or
      rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to
      that of control animals.

PMID- 22856473
TI  - Endometrioma causing sigmoid stricture.

PMID- 22856474
TI  - Hydrocele camouflaging cryptorchidism.

PMID- 22856475
TI  - Portable video education of patients in fiber therapy for quality assessment in
      the outpatient setting.

PMID- 22856476
TI  - Operative management of a large superior mesenteric artery pseudoaneurysm
      secondary to chronic uncontrolled hypertension.

PMID- 22856477
TI  - Myositis ossificans of the forearm after yoga.

PMID- 22856478
TI  - Postoperative inflammatory neuropathy: a challenging diagnosis.

PMID- 22856479
TI  - An adult case of intestinal nonrotation causing distal duodenal obstruction.

PMID- 22856480
TI  - Minimally invasive mitral valve surgery: smaller incisions, better outcomes?

PMID- 22856481
TI  - Left inguinal endometriosis.

PMID- 22856482
TI  - An unusual association of cerebral schwannoma, parathyroid adenoma, and papillary
      thyroid carcinoma.

PMID- 22856483
TI  - Role of Calendula extract in treatment of anal fissures.

PMID- 22856484
TI  - Gastric adenocarcinoma associated with gastritis cystica profunda in an
      unoperated stomach.

PMID- 22856485
TI  - Diagnostic difficulties associated with peritoneal tuberculosis.

PMID- 22856486
TI  - Use of computed tomography findings and contrast extravasation in predicting the
      need for embolization with pelvic fractures.
AB  - Transarterial embolization (AE) can be a lifesaving procedure for severe
      hemorrhage associated with pelvic fractures. The purpose of this study was to
      identify demographic and radiographic findings that predict the need for
      embolization. We performed a retrospective review of all patients  with at least
      one pelvic fracture and admission to the intensive care unit over a 35-month
      period. Computed tomography (CT) and pelvic radiographs were reviewed. Patient
      demographics, outcomes, time to angiography, and whether or not embolization was
      performed were determined. Statistical  analysis was used to determine factors
      associated with the need for AE. Of the 327 total patients with pelvic fractures,
      317 underwent CT scanning. Forty-four patients (13.5%) underwent angiography and
      25 (7.6%) required therapeutic embolization. There were 39 total deaths (11.6%)
      with five  deaths related to pelvic hemorrhage (1.5%). Multivariate analysis
      revealed that age older than 55 years (odds ratio [OR], 1.06; P < 0.001),
      systolic blood pressure less than 90 mmHg in the emergency department (OR, 11.64;
      P = 0.0008), and CT extravasation (OR, 147.152; P  < 0.0001) were significantly
      associated with the need for embolization. Contrast extravasation was not present
      in 25 per cent of patients requiring therapeutic AE. The presence of contrast
      extravasation is highly associated with the need for pelvic embolization in
      patients with pelvic fractures,  but its absence does not exclude the need for
      pelvic angiography.

PMID- 22856487
TI  - Evaluation of preoperative risk factors for converting laparoscopic to open
      cholecystectomy.
AB  - Performing laparoscopic cholecystectomy (LC) always carries the risk of having to
      convert from laparoscopic to open cholecystectomy (LOC). Being able to identify
      these patients preoperatively may allow better preoperative planning and lowering
      operative cost. All LC and LOC were performed  by the Eastern Virginia Medical
      School Department of Surgery retrospectively identified between January 2008 and
      December 2009. Preoperative risk factors identified in both groups included: age,
      gender, body mass index greater than 30 kg/m(2), diabetes mellitus, previous
      upper abdominal  surgery, previous abdominal surgery, presence of pericholecystic
      fluid, gallbladder wall thickness greater than 3 mm, preoperative diagnosis of
      acute cholecystitis, and pancreatitis. Reasons for conversion in the LOC group
      were identified from the operative note. A total of 346 LC and LOC  were
      identified. The LOC group had 41 identified with a conversion rate of 11.9 per
      cent. The LOC group was compared with 100 randomly chosen LC. Risk factors that
      reached statistical significance for conversion included advanced age, male
      gender, previous upper abdominal surgery, preoperative  diagnosis of acute
      cholecystitis, and gallbladder wall thickness greater than 3 mm (P = 0.0009).
      Average operative time was higher in LOC compared with open cholecystectomy (123
      minutes average vs 109 minutes average). Of the reasons for conversion, the
      degree of inflammation  was the most common (51.2%). Preoperative risk factors
      that were associated with need for conversion were advanced age, male gender,
      previous upper abdominal surgery, preoperative diagnosis of acute cholecystitis,
      and pericholecystitic fluid. In patients who have all of these risk factors,  we
      recommend starting with an open cholecystectomy. This will save operative time
      and overall cost.

PMID- 22856488
TI  - Solid organ injury grading in trauma: accuracy of grading by surgical residents.
AB  - The American Association for the Surgery of Trauma developed an Organ Injury
      Scale for management of patients with splenic, kidney, or liver injuries. Despite
      widespread use of the guidelines, the person who determines the injury grade
      varies among institutions. Our purpose was to determine  the accuracy and
      interobserver agreement between surgical residents and a radiologist in grading
      solid organ injuries. We retrospectively reviewed patients with solid organ
      injuries from January 2009 to May 2010 and compared the grade of solid organ
      injuries by a single resident with grades  by a single blinded radiologist using
      a paired t test, analysis of variance, or Kruskal-Wallis. Computed tomography
      scans of 58 patients with splenic injuries, 43 with liver injuries, and 16 with
      kidney injuries were reviewed. Average grades for splenic injuries were 2.5 and
      2.4 (radiologist/resident);  liver injuries, 2.6 and 2.1; and kidney injuries,
      2.7 and 2.8. There were no significant differences in grading by the radiologist
      and resident for splenic and kidney injuries; however, equal values were only
      achieved in 43 and 38 per cent, respectively. There was a significant difference 
      (average rating difference 0.54, P = 0.0002) in grading between the radiologist
      and resident for liver injuries with only 35 per cent having equal values and the
      radiologist grading on average 0.5 points higher than the resident. No
      demographic, injury, or outcome variables were significantly  associated with
      interobserver variability (P > 0.05). Despite a significant difference for liver
      injury grading, interobserver agreement between residents and a single
      radiologist was low. Clinical implications and the impact on outcomes related to
      interobserver variations require  further study.

PMID- 22856489
TI  - Readmissions after pancreaticoduodenectomy: efforts need to focus on patient
      expectations and nonhospital medical care.
AB  - Readmissions after operations are a burden. This study was undertaken to
      determine factors predicting readmissions after pancreaticoduodenectomy. Since
      1991, patients undergoing pancreaticoduodenectomy have been prospectively
      followed. Nineteen per cent of 913 patients were readmitted  within 30 days after
      discharge from pancreaticoduodenectomy. The causes for readmissions were
      reviewed. Median data are presented. All patients had preoperative comorbidities;
      most common were cardiovascular (26%), gastrointestinal (23%), or endocrine
      (15%). Twenty-nine per cent had extended  pancreaticoduodenectomy, including
      major vascular resections. The most common reasons for readmission were:
      nausea/vomiting (26%), wound infection (15%), and abdominal pain (18%). Gender,
      body mass index, duration of operation, blood loss, length of stay, pathology,
      American Joint Committee  on CancerTM stage, and margin status did not predict
      readmission. Patients being readmitted were younger (65 vs 69 years, P < 0.001)
      and had more comorbidities (P < 0.001). Readmission did not curtail long-term
      survival. Pancreaticoduodenectomy is a complex  operation undertaken in patients
      with notable comorbidities. Readmissions occur frequently after
      pancreaticoduodenectomy and patients with more comorbidities are at particular
      risk. Readmissions are not generally the result of complications specific to
      pancreaticoduodenectomy, but seem more  related to ill health, inaccessible
      nonhospital medical care, and poor expectations. Efforts must focus on patient
      expectations, intermediate care, home health care, and improving medical care
      after discharge.

PMID- 22856490
TI  - Parathyroidectomies using intraoperative parathormone monitoring: when should we
      stop measuring intraoperative parathormone levels?
AB  - Intraoperative parathyroid hormone monitoring (IOPM), in use for the last 15
      years, has facilitated focused parathyroidectomy. We undertook this study to
      determine if a drop in IOPT hormone levels below 50 per cent of baseline were
      sufficient to terminate the procedure. We conducted  a retrospective chart review
      (January 2007 to September 2010) of 104 patients who underwent initial
      parathyroidectomies with IOPM by general surgeons for primary
      hyperparathyroidism. Patients were followed up for serum calcium levels (range, 6
      to 48 months). The number of specimens excised  was significantly decreased when
      IOPT hormone levels dropped to greater than 50 per cent and came within the
      normal range earlier. Moreover, for single-gland parathyroid adenomas, once the
      parathyroid hormone values dropped to less than 50 per cent in the 5-minute
      sample, they continued to  decrease in the subsequent samples. In 23 cases
      requiring further exploration, the parathyroid hormone values had already
      decreased to greater than 50 per cent in 14 cases but had not normalized
      (reference range, 8 to 74), leading to additional exploration. However,
      subsequent pathologic analysis  showed that the initial gland removed was the
      adenoma in all these cases. A drop in the initial 5-minute parathyroid hormone
      value to less than 50 per cent of the baseline should serve as sufficient
      evidence to terminate the procedure. This would translate into significant
      laboratory and personnel  cost savings over time. However, this should be
      carefully correlated with preoperative ultrasound/sestamibi findings.

PMID- 22856491
TI  - Ventilator-associated pneumonia: depends on your definition.
AB  - Reduction of hospital-acquired infections is a patient safety goal and regularly
      monitored by Performance Improvement committees. There is discordance between the
      ventilator-associated pneumonia (VAP) rate reported by the Infection Control
      Committee (ICC) and that observed by our Trauma  Service. To investigate this
      difference, a retrospective evaluation of cases of VAP diagnosed on a single
      service was undertaken. A prospectively collected database was queried for VAP in
      intensive care unit patients between January 2010 and June 2011. This was
      compared with the list of mechanically  ventilated patients provided by the ICC.
      Comparison for criteria used to diagnose pneumonia, ventilator day of the
      diagnosis, was recorded. The ICC identified two VAPs from 136 potential patients
      compared with the Trauma Service identifying 36 VAPs. A difference in diagnostic
      criteria between  the ICC and the Trauma Service focused on use of the National
      Nosocomial Infection Survey (NNIS) algorithm versus quantitative microbiology
      from bronchoalveolar lavage specimens. Thirty-five of 36 Trauma Service VAPs were
      not identified as VAPs by the NNIS algorithm as a result of the  chest
      radiographs. Application of differing definitions of VAP results in markedly
      different VAP rates. The difference has significant implications as infection
      rates are increasingly reported as a quality metric.

PMID- 22856492
TI  - Breakdown of the consent process at a quaternary medical center: our full
      disclosure.
AB  - Circumstances may arise in the intensive care unit (ICU) when the physician is
      unable to obtain informed consent. We undertook this study to determine the
      variations in the consent process. An anonymous survey was distributed to all
      critical care nurses (RN), resident physicians (RES),  advanced practitioners
      (AP), and attending physicians (ATT). Participants were asked to describe the
      risks of nine common ICU procedures (central venous line, peripherally inserted
      central catheter, bronchoscopy, tube thoracostomy, tracheostomy, vena cava
      filter, angioembolization, image-guided  drainage, and percutaneous endoscopic
      gastrostomy tube). Participants were also asked which member of the healthcare
      team should obtain consent. All groups were compared with ATT responses and RN
      responses were compared with the remaining groups. The response rate was 134 of
      610 participants  (22%) with 51 per cent RN (n = 68), 17 per cent RES (n = 23), 7
      per cent AP (n = 9), and 25 per cent ATT (n = 34). Compared with ATT, RN
      assessment of important risks varied significantly for eight of nine procedures.
      RES responses varied in three procedures. A minority believed that nurses  should
      obtain consent. However, many physicians (34% ATT and 27% RES) denied having
      informed consent discussions with 50 per cent or more of their patients. This
      study has exposed a wide variation in consent practices. Future efforts to
      standardize consent processes are needed to protect patients  and physicians.

PMID- 22856493
TI  - Incisional hernia risk after hand-assisted laparoscopic surgery.
AB  - Hand-assisted laparoscopic surgery (HALS) bridges traditional open surgery and
      pure laparoscopy. The HALS technique provides the necessary site for organ
      retrieval, reduces operative time, and realizes the postoperative benefits of
      laparoscopic techniques. Although the reported rates  of incisional hernia should
      be theoretically low, we sought to determine our incidence of hernia after HALS
      procedures. A retrospective review of all HALS procedures was performed from July
      2006 to June 2011. All patients who developed postoperative incisional hernias at
      the hand port site  were confirmed by imaging or examination findings. Patient
      factors were reviewed to determine any predictors of hernia formation. Over the 5
      years, 405 patients undergoing HALS procedures were evaluated: colectomy (264),
      nephrectomy (107), splenectomy/pancreatectomy (18), and ostomy reversal  (10).
      The overall incidence of incisional hernia was 10.6 per cent. There were three
      perioperative wound dehiscences. The mean body mass index was significantly
      higher in the hernia group versus the no hernia cohort (32.1 vs 29.2 kg/m(2); P =
      0.001). The hernia  group also had a higher incidence of renal disease (18.6 vs
      7.2%; P = 0.018). Mean time to hernia formation was 11.4 months (range, 1 to 57
      months). Follow-up was greater than 12 months in 188 (46%) of patients, in which
      the rate of incisional hernia was 17 per cent. The rate  of incisional hernia
      formation after hand-assisted laparoscopic procedures is higher than the reported
      literature. Because the mean time to hernia development is approximately 1 year,
      it is important to follow these patients to this end point to determine the true
      incidence of incisional hernia  after hand-assisted laparoscopy.

PMID- 22856494
TI  - Dedicated tracking of patients with retrievable inferior vena cava filters
      improves retrieval rates.
AB  - Retrievable IVC filters (R-IVCF) are associated with multiple complications,
      including filter migration and deep venous thrombosis. Unfortunately, most series
      of R-IVCF show low retrieval rates, often due to loss to follow-up. This study
      demonstrates that actively tracking R-IVCF improves  retrieval. Trauma patients
      at one institution with R-IVCF placed between January 2007 and January 2011 were
      tracked in a registry with a goal of retrieval. These were compared to a control
      group who had R-IVCF placed previously (December 2005 to December 2006). Outcome
      measures include filter  retrieval, retrieval attempts, loss to follow-up, and
      time to filter retrieval. We compared 93 tracked patients with R-IVCF with 20
      controls. The baseline characteristics of the groups were similar. Tracked
      patients had significantly higher rates of filter retrieval (60% vs 30%, P  =
      0.02) and filter retrieval attempts (70% vs 30%, P = 0.002) and were
      significantly less likely to be lost to follow-up (5% vs 65%, P < 0.0001). Time
      to retrieval attempt was 84 days in the registry versus 210 days in the control
      group, which trended  towards significance (P = 0.23). Tracking patients with R
      IVCF leads to improved retrieval rates, more retrieval attempts, and decreased
      loss to follow up. Institutions should consider tracking R-IVCF to maximize
      retrieval rates.

PMID- 22856495
TI  - Can CT angiography replace conventional bi-planar angiography in the management
      of severe scapulothoracic dissociation injuries?
AB  - Severe scapulothoracic dissociation (SSTD) (Type III or IV; Zelle classification)
      is often life-threatening and is commonly associated with other devastating
      injuries. Rapid evaluation, including of the vascular system, is critical to
      limit the time to definitive therapy. CT angiography  (CTA) has evolved as a
      diagnostic tool, replacing angiography (angio) as it can simultaneously evaluate
      bony, soft tissue, and vascular injuries. We hypothesized that CTA would be
      useful in evaluating patients with SSTD. We retrospectively reviewed the trauma
      registry between June 2002 and  June 2010 to identify patients over 18 years of
      age who sustained SSTD. Patients that were transferred or died before diagnostic
      imaging were excluded. Comparisons were made between the group that underwent
      angio before surgery compared with CTA with regards to outcome and length of
      hospital  and intensive care unit stay. Fourteen patients were identified with
      Type III or IV SSTD over the study period. In the CTA group, mean Injury Severity
      Score was higher, but time to definitive operative intervention was significantly
      shorter. There was no difference in amputation rates or mortality.  Replacing
      arteriography with CTA in the preoperative workup of patients with SSTD reduces
      time to surgery. Despite a greater injury severity in the group in which CTA was
      used as the primary imaging modality, length of stay, amputation rates, and
      mortality were no different. CTA can be safely  used to evaluate patients with
      suspected SSTD.

PMID- 22856496
TI  - Initial suction evacuation of traumatic hemothoraces: a novel approach to
      decreasing chest tube duration and complications.
AB  - Between 2 and 4.4 per cent of all patients with trauma chest tubes develop
      retained hemothoraces. Retained hemothoraces prolong chest tube duration and
      hospital length of stay, and increase infectious complications like empyema.
      Early surgical drainage of retained hemothoraces has been  shown to decrease
      complications and reduce hospital length of stay. However, the high resource and
      expertise requirement may limit the widespread applicability of surgical
      drainage. We present the results of a relatively simple and novel intervention
      for traumatic hemothoraces undertaken by  our faculty to shorten chest tube
      duration and prevent empyema formation. At our Level I trauma center, 10 trauma
      patients underwent initial suction evacuation of their traumatic hemothoraces
      using a sterile suction catheter before chest tube placement. Compared with
      propensity matched controls,  patients that underwent initial suction evacuation
      experienced significantly shorter chest tube duration (4.2 +/- 1.9 vs 5.8 +/- 2.3
      days, P = 0.04). Also, in this population, there was an 8.2 per cent decrease in
      the number of patients that developed empyema or required  additional drainage.
      Our study suggests that initial suction evacuation of traumatic hemothoraces is
      an effective and relatively easy intervention that reduces the duration of chest
      tube therapy, empyema formation, and the need for additional surgical
      intervention.

PMID- 22856497
TI  - A comparative analysis between laparoscopic and open ventral hernia repair at a
      tertiary care center.
AB  - Laparoscopic ventral hernia repair reportedly yields lower postoperative
      complications than open repair. We hypothesized that patients undergoing
      laparoscopic repair would have lower postoperative infectious outcomes. Also,
      certain preoperative patient characteristics and preoperative  hernia
      characteristics are hypothesized to increase complication risk in both groups.
      All ventral hernia repairs performed at University of Virginia from January 2004
      to January 2006 were reviewed. Primary outcomes included wound healing
      complications and hernia recurrence. Categorical data  were analyzed with chi(2)
      and Fisher's exact tests. Continuous variables were evaluated with independent t
      tests and Mann-Whitney U tests. Multivariable logistic regression was performed.
      A total of 268 repairs (110 open, 158 laparoscopic) were evaluated. Patient and 
      hernia characteristics were similar between groups, though the percents of wound
      contamination (5.4% vs 0.6%; P = 0.02) and simultaneous surgery (7.2% vs 0%; P =
      0.001) were greater in the open procedures. Univariate analysis also revealed
      that open cases had a  greater incidence of postoperative superficial surgical
      site infection (SSI) (30.0% vs 10.7%; P < 0.0001). Multivariable analysis
      revealed that both diabetes and open repair were associated with an increased
      risk of superficial SSI (P = 0.019; odds ratio = 3.512; 95%  confidence interval
      = 1.229-10.037 and P = 0.001; odds ratio = 4.6; 95% confidence interval = 1.9
      11.2, respectively). Laparoscopic ventral hernia repair yielded lower rates of
      postoperative superficial SSI than open surgery. Other preoperative patient
      characteristics  and preoperative hernia characteristics, with the exception of
      diabetes, were not found to be associated with an increased risk of postoperative
      complications.

PMID- 22856498
TI  - Total pancreatectomy with islet autotransplantation for chronic pancreatitis: do
      patients with prior pancreatic surgery have different outcomes?
AB  - Total pancreatectomy with immediate islet autotransplantation (IAT) can be an
      effective therapy in patients with chronic pancreatitis. Patient selection
      criteria for radical resection are not well defined. The impact of prior
      pancreatic surgery on quality of life outcomes in patients  undergoing IAT is
      evaluated. A retrospective review of a prospectively collected database of
      patients undergoing pancreatectomy with islet autotransplantation was undertaken.
      Patients having undergone prior pancreatic resection and/or drainage procedures
      were compared with those without prior  pancreatic operative history. Sixty-one
      patients underwent pancreatectomy with IAT for pancreatitis. Twenty-three
      patients had a prior history of pancreatic surgery (Group S); 38 had no prior
      history of pancreatic surgery (Group NS). Demographics between the groups were
      similar. Patients in  Group S took more daily oral morphine equivalents and had a
      lower psychological quality of life preoperatively. Operative times and blood
      loss were similar between the patient groups. Islet yields were lower for
      patients in Group S. Postoperatively, daily insulin requirements at 6 months and 
      1 year trended higher in Group S. Postoperative quality of life scores at 6
      months were improved and similar between the groups. Quality of life metrics
      continued to improve beyond 1 year of follow-up, with a trend toward greater
      improvement in the NS Group. Total pancreatectomy for chronic  pancreatitis
      improves quality of life in patients with and without a prior history of
      pancreatic surgery. This study demonstrates that IAT without preceding pancreatic
      surgery may enhance outcomes measured by long term insulin requirements and
      quality of life.

PMID- 22856499
TI  - Delaying an appendectomy: is it safe?
AB  - Appendicitis has always been an indication for an urgent operation, as delay is
      thought to lead to disease progression and therefore worse outcomes. Recent
      studies suggest that appendectomy can be delayed slightly without worse outcomes,
      however the literature is contradictory. The  goal of our study was to examine
      the relationship between this delay to surgery and patient outcomes. We reviewed
      all patients that underwent an appendectomy in our institution from January 2009
      to December 2010. We recorded the time of surgical diagnosis from when both the
      surgical consult  and the CT scan (if done) were completed. The delay from
      surgical diagnosis to incision was measured, and patients were divided into two
      groups: early (<=6 hours delay) and late (>6 hours delay). Outcome measures were
      30-day complication rate, length of stay, perforation rate, and laparoscopic  to
      open conversion rate. Three hundred and seventy-seven patients had appendectomies
      in the study period, and 35 patients were excluded as per the exclusion criteria
      leaving 342 in the study: 269 (78.7%) in the early group and 73 (21.3%) in the
      late group. Complications occurred in 21 patients  (6.1%) with no difference
      between the groups: 16/253 (5.9%) in the early group and 5/73 (6.8%) in the late
      group (P = 0.93, chi(2)). The mean (+/- standard deviation) length of stay was
      86.1 +/- 67.1 hours in the early group, and 95.9 +/- 73.0 hours in the  late
      group. This difference was not significant (P = 0.22). Delaying an appendectomy
      more than 6 hours, but less than 24 hours from diagnosis is safe and does not
      lead to worse outcomes. This can help limit the disruption to the schedules of
      both the surgeon and the operating room.

PMID- 22856500
TI  - Screening human immunodeficiency virus-positive men for anal intraepithelial
      neoplasia.
AB  - Squamous cell carcinoma of the anus is rare, but more common in men with human
      immunodeficiency virus (HIV). We describe our findings in 50 biopsies done on 37
      HIV-positive men over 5 years. The men were referred from our HIV clinic for
      abnormal cytology on anal pap or anal condyloma.  Thirty-seven patients were
      referred from the HIV clinic for abnormal cytology on anal pap or the presence of
      anal condyloma. Biopsies were done in the operating room using acetic acid to
      visually localize areas of dysplasia. If no abnormalities were seen, biopsies
      were taken from each quadrant  of the anus. A retrospective review was done for
      biopsy indication, pathology, recurrence, and correlation with anal pap results.
      On initial biopsy, anal condyloma conferred the presence of anal intraepithelial
      neoplasia (AIN) in 64.7 per cent (11 of 17), abnormal paps in 83.3 per cent (10 
      of 12), and both in 50 per cent (3 of 6). Patients with anal condyloma had AIN in
      an average of 2.5 quadrants whereas those with abnormal cytology had AIN in 2.3
      quadrants. Thirty-four of 50 biopsies showed abnormalities (68%), with AIN
      present in 32 cases, one case of carcinoma in situ,  and one case of invasive
      carcinoma. Aldara was used nine times with improvement in four cases. In HIV
      positive men, the presence of condyloma warrants surgical biopsy. Performing anal
      cytology on patients with anal condyloma did not increase the rate of positive
      results. Patients with AIN  often had disease in more than two quadrants, making
      surgical excision problematic.

PMID- 22856501
TI  - They are not just little adults: angioembolization improves salvage of high grade
      IV-V blunt splenic injuries in adults but not in pediatric patients.

PMID- 22856502
TI  - Can large gauge core biopsies for high risk benign breast lesions eliminate the
      need for excisional biopsy: a correlation between breast biopsy and final
      surgical pathology.

PMID- 22856503
TI  - Effect of ration size on fillet fatty acid composition, phospholipid allostasis
      and mRNA expression patterns of lipid regulatory genes in gilthead sea bream
      (Sparus aurata).
AB  - The effect of ration size on muscle fatty acid (FA) composition and mRNA
      expression levels of key regulatory enzymes of lipid and lipoprotein metabolism
      have been addressed in juveniles of gilthead sea bream fed a practical diet over
      the course of an 11-week trial. The experimental setup included three feeding
      levels: (i) full ration until visual satiety, (ii) 70 % of satiation and (iii) 70
      % of satiation with the last 2 weeks at the maintenance ration. Feed restriction
      reduced lipid content of whole body by 30 % and that of fillet by 50 %. In this
      scenario, the FA composition of fillet TAG was not altered by ration size,
      whereas that of phospholipids was largely modified with a higher retention of
      arachidonic acid and DHA. The mRNA transcript levels of lysophosphatidylcholine
      acyltransferases, phosphatidylethanolamine N-methyltransferase and FA desaturase
      2 were not regulated by ration size in the present experimental model. In
      contrast, mRNA levels of stearoyl-CoA desaturases were markedly down-regulated by
      feed restriction. An opposite trend was found for a muscle-specific lipoprotein
      lipase, which is exclusive of fish lineage. Several upstream regulatory
      transcriptions were also assessed, although nutritionally mediated changes in
      mRNA transcripts were almost reduced to PPARalpha and beta, which might act in a
      counter-regulatory way on lipolysis and lipogenic pathways. This gene expression
      pattern contributes to the construction of a panel of biomarkers to direct marine
      fish production towards muscle lean phenotypes with increased retentions of long
      chain PUFA.

PMID- 22856505
TI  - Service contacts prior to death in people dying by suicide in the Scottish
      Highlands.
AB  - INTRODUCTION: Many people who die by suicide have been in contact with health
      services prior to their death. This study examined service contacts in people in
      urban and rural areas of the Scottish Highlands. METHODS: Highland residents
      dying by suicide or undetermined intent in 2001-2004 were identified using
      routine death records. Health service databases were searched to identify general
      hospital, mental health and general practice notes. RESULTS: 177 residents died
      in the time period (136 males). At least one type of record was identified on 175
      people, including general practice records (167 people, 94.4%), psychiatric
      hospital records (n=87, 49.2%) and general hospital records (n=142, 80.2%). Of
      these, 52.5% had been in contact with at least one health service in the month
      before their death, including 18.6% with mental health services, and 46.4% with
      general practice. In total, 68.9% had a previous diagnosis of mental illness,
      52.5% of substance misuse problems, and 40.1% of self-harm. The commonest mental
      illness diagnosis was depression (n=97, 54.8%). There was no difference in rates
      of GP contact in rural and urban areas. Of those dying in urban areas, 32% had
      been in contact with mental health services in the previous month, compared with
      21% in Accessible Rural/Accessible Small Towns, and 11% in Remote Rural/Remote
      Small Towns (p<0.01). People in rural areas were less likely to have had contact
      with mental health services in the year before their death (p<0.01), and to have
      had lower recorded lifetime rates of mental health service contact (p<0.001),
      deliberate self-harm (p<0.005) and mental illness (p<0.001). CONCLUSIONS: Overall
      service contact rates prior to death by suicide were very similar to the results
      of a previous meta-analysis. Rates of contact with specialist mental health
      services were significantly lower in rural than urban areas, and this finding
      increased with greater rurality.

PMID- 22856504
TI  - Structured self-management education maintained over two years in insufficiently
      controlled type 2 diabetes patients: the ERMIES randomised trial in Reunion
      Island.
AB  - BACKGROUND: Self-management education programs can reduce the complications and
      mortality in type 2 diabetes. The need to structure these programs for outpatient
      and community care with a vision for long-term maintenance has been recognised.
      In Reunion Island, an area affected by epidemiological and nutritional
      transition, diabetes affects 18% of the adult population over 30 years, with
      major social disparities, poor glycaemic control and frequent cardiovascular
      complications. METHODS/DESIGN: ERMIES is a randomised controlled trial designed
      to test the efficacy of a long-term (2 years) structured group self management
      educational intervention in improving blood glucose in non-recent, insufficiently
      controlled diabetes. After an initial structured educational cycle carried out
      blind for the intervention arm, patients will be randomised in two parallel group
      arms of 120 subjects: structured on-going group with educational intervention
      maintained over two years, versus only initial education. Education sessions are
      organised through a regional diabetes management network, and performed by
      trained registered nurses at close quarters. The educational approach is
      theoretically based (socio-constructivism, social contextualisation, empowerment,
      action planning) and reproducible, thanks to curricula and handouts for educators
      and learners. The subjects will be recruited from five hospital outpatient
      settings all over Reunion Island. The main eligibility criteria include: age >=18
      years, type 2 diabetes treated for more than one year, HbA1c >= 7.5% for >=3
      months, without any severe evolving complication (ischaemic or proliferative
      retinopathy, severe renal insufficiency, coronaropathy or evolving foot lesion),
      and absence of any major physical or cognitive handicap. The primary outcome
      measure is HbA1c evolution between inclusion and 2 years. The secondary outcome
      measures include anthropometric indicators, blood pressure, lipids, antidiabetic
      medications, level of physical activity, food ingestion, quality of life, social
      support, anxiety, depression levels and self-efficacy. An associated nested
      qualitative study will be conducted with 30 to 40 subjects in order to analyse
      the learning and adaptation processes during the education cycles, and throughout
      the study. CONCLUSIONS: This research will help to address the necessary but
      difficult issue of structuring therapeutic education in type 2 diabetes based on:
      efficacy and potential interest of organising on-going empowerment group
      sessions, at close quarters, over the long term, in a heterogeneous socioeconomic
      environment. TRIAL REGISTRATION: ID_RCB number: 2011-A00046-35Clinicaltrials.gov
      number: NCT01425866.

PMID- 22856506
TI  - Long directional interactions (LDIs) in oligomeric cofacial silicon
      phthalocyanines and other oligomeric and polymeric cofacial phthalocyanines.
AB  - Crystal structures have been determined for the three-member set of cofacial
      silicon phthalocyanines, ((n-C(6)H(13))(3)SiO)[SiPcO](1-3)(Si(n-C(6)H(13))(3)).
      The staggering angles between adjacent rings in the dimer and trimer of this set
      are ~16 degrees . The interactions leading to these angles have been investigated
      by the atoms-in-molecules (AIM) and reduced-density-gradient (RDG) methods. The
      results show that long directional interactions (LDIs) are responsible for these
      angles. A survey of the staggering angles in various cofacial phthalocyanines
      described in the literature has revealed the existence of significant LDIs in a
      number of them. It is apparent that in many cases the ability of LDIs to dominate
      the forces giving rise to the staggering angles observed in cofacial
      phthalocyanines depends on their inter-ring separations.

PMID- 22856507
TI  - Methods for evaluating cervical range of motion in trauma settings.
AB  - Immobilisation of the cervical spine is a common procedure following traumatic
      injury. This is often precautionary as the actual incidence of spinal injury is
      low. Nonetheless, stabilisation of the head and neck is an important part of pre
      hospital care due to the catastrophic damage that may follow if further
      unrestricted movement occurs in the presence of an unstable spinal injury.
      Currently available collars are limited by the potential for inadequate
      immobilisation and complications caused by pressure on the patient's skin,
      restricted airway access and compression of the jugular vein. Alternative
      approaches to cervical spine immobilisation are being considered, and the
      investigation of these new methods requires a standardised approach to the
      evaluation of neck movement. This review summarises the research methods and
      scientific technology that have been used to assess and measure cervical range of
      motion, and which are likely to underpin future research in this field. A
      systematic search of international literature was conducted to evaluate the
      methodologies used to assess the extremes of movement that can be achieved in six
      domains. 34 papers were included in the review. These studies used a range of
      methodologies, but study quality was generally low. Laboratory investigations and
      biomechanical studies have gradually given way to methods that more accurately
      reflect the real-life situations in which cervical spine immobilisation occurs.
      Latterly, new approaches using virtual reality and simulation have been
      developed. Coupled with modern electromagnetic tracking technology this has
      considerable potential for effective application in future research. However, use
      of these technologies in real life settings can be problematic and more research
      is needed.

PMID- 22856508
TI  - Promotion and inhibition of cardiac hypertrophy by A-kinase anchor proteins.
AB  - Originally identified as mediators of cyclic adenosine monophosphate (cAMP) and
      protein kinase A signaling, A-kinase anchor proteins (AKAPs) are now recognized
      as a diverse family of molecular scaffolds capable of interacting with many other
      proteins. Members of the AKAP family within the heart can take on either pro- or
      anti-hypertrophic roles by interacting with a myriad of protein kinases and
      phosphatases in the process. AKAPs often form the core of large signaling
      complexes (or signalosomes) that allow multiple pathways to converge and
      functionally intertwine. Approximately 30% of AKAPs discovered to date are
      expressed in the heart, but the functions of many of these remain to be
      discovered. This review focuses on AKAPs that have been demonstrated to play
      roles in mediating cardiac hypertrophy.

PMID- 22856509
TI  - Antiviral activity of acidic polysaccharides from Coccomyxa gloeobotrydiformi, a
      green alga, against an in vitro human influenza A virus infection.
AB  - The extracts prepared from green algae are reported to possess a variety of
      biological activities including antioxidant, antitumor and antiviral activities.
      The acidic polysaccharide fraction from a green alga Coccomyxa gloeobotrydiformi
      (CmAPS) was isolated and the antiviral action on an in vitro infection of
      influenza A virus was examined. CmAPS inhibited the growth and yield of all
      influenza A virus strains tested, such as A/H1N1, A/H2N2, A/H3N2 and A/H1N1
      pandemic strains. The 50% inhibitory concentration of CmAPS on the infection of
      human influenza A virus strains ranged from 26 to 70 ug/mL and the antiviral
      activity of CmAPS against influenza A/USSR90/77 (H1N1) was the strongest. The
      antiviral activity of CmAPS was not due to the cytotoxicity against host cells.
      The antiviral activity of CmAPS required its presence in the inoculation of virus
      onto MDCK cells. Pretreatment and post-treatment with CmAPS was ineffective for
      the antiviral activity. CmAPS inhibited influenza A virus-induced erythrocyte
      hemagglutination and hemolysis. Taken together, CmAPS was suggested to exhibit
      the anti-influenza virus activity through preventing the interaction of virus and
      host cells. The detailed antiviral activity of CmAPS is discussed.

PMID- 22856510
TI  - Re-emergence of brucellosis in cattle in France and risk for human health.
AB  - A case of human brucellosis was diagnosed in France in January 2012. The
      investigation demonstrated that the case had been contaminated by raw milk cheese
      from a neighbouring dairy farm. As France has been officially free of bovine
      brucellosis since 2005, veterinary investigations are being conducted to
      determine the origin of the infection and avoid its spread among other herds.
      Hypotheses about the source of this infection are discussed.

PMID- 22856511
TI  - Differences in hepatitis B infection rate between ethnic groups in antenatal
      women in Birmingham, United Kingdom, May 2004 to December 2008.
AB  - Hepatitis B virus (HBV) is a major cause of morbidity and mortality worldwide.
      Although the United Kingdom (UK) prevalence of HBV is low, it is increasing.
      There is some evidence that the rate of infection is much higher in some
      populations living in Britain of non-white ethnicity or who were not born in
      Britain, compared with the British-born white population. We examined the
      prevalence of HBV infection in pregnant women through hepatitis B surface antigen
      (HBsAg) or e-antigen (HBeAg) in Birmingham UK between May 2004 and December 2008
      and the effect of ethnicity on the relative risk of infection. There was a
      significant increase in the number of antenatal HBV infections detected over the
      study period from 106 cases in 2005 to 161 cases in 2008 (p=0.037). Women who
      define themselves as of black African, non-British white and Pakistani ethnicity
      had a markedly elevated rate of HBV infection (relative risk (RR): 11.25, 5.87
      and 2.33 respectively) compared to the England average. Health organisations that
      serve populations with a high or increasing proportion of women originating from
      intermediate and high HBV prevalence areas of the world such as Africa, some
      parts of Europe and Asia, should anticipate a need for perinatal and postnatal
      prophylaxis to children born to HBV infected mothers.

PMID- 22856512
TI  - Long-term control of vancomycin-resistant Enterococcus faecium at the scale of a
      large multihospital institution: a seven-year experience.
AB  - Repeated outbreaks of vancomycin-resistant Enterococcus faecium (VRE) occurred
      between 2004 and 2010 in Assistance Publique--Hopitaux de Paris (AP-HP), a 23,000
      bed multi-hospital institution. From August 2004 to December 2005, the French
      guidelines for preventing cross-transmission of multiresistant bacteria were
      applied. Because the number of VRE cases continued to increase, an institutional
      control programme was implemented from January 2006 onwards: it foresees stopping
      transfer of VRE and contact patients, separating VRE and contact patients in
      distinct cohorts, intervention of a central infection control team to support
      local teams, and quick application of measures as soon as first VRE cases are
      identified. Between August 2004 and December 2010, 45 VRE outbreaks occurred in
      21 of the 38 AP-HP hospitals, comprising 533 cases. Time series analysis showed
      that the mean number of cases increased by 0.8 cases per month (95% confidence
      interval (CI): 0.3 to 1.3, p=0.001) before, and decreased by 0.7 cases per month
      after implementation of the programme (95% CI: -0.9 to -0.5, p<0.001), resulting
      in a significant trend change of -1.5 cases per month (95% CI: -2.1 to -0.9,
      p<0.001). The number of cases per outbreak was significantly lower after
      implementation of the programme. A sustained and coordinated strategy can control
      emerging bacteria at the level of a large regional multihospital institution.

PMID- 22856514
TI  - Genome-wide identification, evolutionary and expression analyses of putative Fe-S
      biogenesis genes in rice (Oryza sativa).
AB  - Iron-sulfur (Fe-S) proteins are ubiquitous in nature and carry Fe-S clusters
      (ISCs) as prosthetic groups that are essential in maintaining basic biological
      processes such as photosynthesis, respiration, nitrogen fixation, and DNA repair.
      In the present investigation, a comprehensive genome-wide analysis was carried
      out to find all the genes involved in the formation of ISCs in rice ( Oryza
      sativa  L.) through a systematic EST and genomic DNA sequence data mining. This
      analysis profiled 44 rice ISC genes (OsISCs) that were identified using in silico
      analysis. Multiple sequence alignment and phylogenetic analysis revealed that
      these genes were highly conserved among bacteria, fungi, animals, and plants. EST
      analysis and RT-PCR assays demonstrated that all OsISCs were active and that the
      transcript abundance of some OsISCs was tissue specific. The results of this
      study will assist further investigations to identify and elucidate the structural
      components involved in the assembly, biogenesis, and regulation of OsISCs. Thus,
      the outcome of the present study provides basic genomic information for the OsISC
      and will pave the way for elucidating the precise role of OsISCs in plant growth
      and development in the future. Also, it may enable us in the future to enhance
      the crop yield, uptake of Fe, and protection against abiotic and biotic stress.

PMID- 22856515
TI  - Investigations of the distribution and persistence of Salmonella and
      ciprofloxacin-resistant Escherichia coli in turkey hatcheries in the UK.
AB  - This study aimed at gaining information on the presence of Salmonella in UK
      turkey hatcheries and possible epidemiological links between breeding farms,
      hatcheries and finishing farms. The presence of ciprofloxacin-resistant E. coli
      in hatchery samples, as well as in faecal samples from farms, and trends in
      occurrence of resistance were also investigated. Over a 2 year-period, four
      British turkey hatcheries were visited and intensively sampled for the presence
      of Salmonella and ciprofloxacin-resistant E. coli. In two hatcheries, a link
      could be demonstrated between the presence of certain Salmonella serovars in the
      hatcheries and on breeding and finishing farms. Within the hatcheries, serovars
      linked to breeding farms were found more frequently in the poult processing and
      dispatch areas, whereas serovars identified as 'resident hatchery contaminants'
      were predominantly found inside the hatcher cabinets. Ciprofloxacin-resistant
      isolates of S. Senftenberg were identified in one hatchery, which coincided with
      enrofloxacin treatment of some of the breeding flocks. Ciprofloxacin-resistant E.
      coli was found in two hatcheries, and the majority of these isolates showed
      multidrug resistance.

PMID- 22856516
TI  - Oxcarbazepine versus carbamazepine in the treatment of paroxysmal kinesigenic
      dyskinesia.
AB  - Paroxysmal kinesigenic dyskinesia (PKD) is an uncommon neurological disorder,
      consisting of brief attacks of involuntary movements triggered by sudden action.
      Patients with PKD generally respond positively to antiepileptic drugs. We
      compared the efficacy and tolerability of oxcarbazepine (OXC) and carbamazepine
      (CBZ) in the treatment of PKD, in order to find the optimal prescription. This
      retrospective study reviewed monotherapy use of CBZ or OXC in 28 patients with
      PKD during 2005-2011, dividing into two groups. The frequency and severity of
      attacks and adverse events were recorded. Ten patients in the OXC group and 12 in
      the CBZ group continued the therapy for more than 12 months. The 12-month
      retention rate was 76.92% and 80.00%. Both groups showed a marked reduction in
      attack frequency and the degree of reduction did not differ significantly between
      the groups. Side effects in patients with OXC included headache, diplopia, and
      elevated hepatic enzymes, while diplopia, nausea, and leukopenia were recorded in
      CBZ group. Another three cases were found with better tolerance when converted to
      OXC from CBZ for rash, drowsiness, diplopia, and nervousness. In conclusion, OXC
      and CBZ are similarly effective and tolerated in the treatment of PKD, however,
      more evidence from larger and blind prospective trials are needed.

PMID- 22856517
TI  - Mental health first aid for eating disorders: pilot evaluation of a training
      program for the public.
AB  - BACKGROUND: Eating disorders cause significant burden that may be reduced by
      early and appropriate help-seeking. However, despite the availability of
      effective treatments, very few individuals with eating disorders seek treatment.
      Training in mental health first aid is known to be effective in increasing mental
      health literacy and supportive behaviours, in the social networks of individuals
      with mental health problems. Increases in these domains are thought to improve
      the likelihood that effective help is sought. However, the efficacy of mental
      health first aid for eating disorders has not been evaluated. The aim of this
      research was to examine whether specific training in mental health first aid for
      eating disorders was effective in changing knowledge, attitudes and behaviours
      towards people with eating disorders. METHODS: A repeated measures, uncontrolled
      trial was conducted to establish proof of concept and provide guidance on the
      future design of a randomised controlled trial. Self-report questionnaires,
      administered at baseline, post-training and 6-month follow-up, assessed the
      effectiveness of the 4-hour, single session, mental health first aid training.
      RESULTS: 73 participants completed the training and all questionnaires. The
      training intervention was associated with statistically significant increases in
      problem recognition and knowledge of appropriate mental health first aid
      strategies, which were maintained at 6-month follow-up. Sustained significant
      changes in attitudes and behaviours were less clear. 20 participants reported
      providing assistance to someone with a suspected eating disorder, seven of whom
      sought professional help as a result of the first aid interaction. Results
      provided no evidence of a negative impact on participants or the individuals they
      provided assistance to. CONCLUSIONS: This research provides preliminary evidence
      for the use of training in mental health first aid as a suitable intervention for
      increasing community knowledge of and support for people with eating disorders to
      seek appropriate help. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry ACTRN12611001181998.

PMID- 22856518
TI  - Higher incidence of death in multi-vessel coronary artery disease patients
      associated with polymorphisms in chromosome 9p21.
AB  - BACKGROUND: We investigated whether 9p21 polymorphisms are associated with
      cardiovascular events in a group of 611 patients enrolled in the Medical,
      Angioplasty or Surgery Study II (MASS II), a randomized trial comparing
      treatments for patients with coronary artery disease (CAD) and preserved left
      ventricular function. METHODS: The participants of the MASS II were genotyped for
      9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival
      curves were calculated with the Kaplan-Meier method and compared with the log
      rank statistic. We assessed the relationship between baseline variables and the
      composite end-point of death, death from cardiac causes and myocardial infarction
      using a Cox proportional hazards survival model. RESULTS: We observed significant
      differences between patients within each polymorphism genotype group for baseline
      characteristics. The frequency of diabetes was lower in patients carrying GG
      genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared
      to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and
      40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant
      differences in genotype frequencies between double and triple vessel disease
      patients were observed for the rs10757274, rs10757278 and rs1333049. Finally,
      there was a higher incidence of overall mortality in patients with the GG
      genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%,
      11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still
      significantly associated with a 1.75-fold increased risk of overall mortality (p
      = 0.02) even after adjustment of a Cox multivariate model for age, previous
      myocardial infarction, diabetes, smoking and type of coronary anatomy.
      CONCLUSIONS: Our data are in accordance to previous evidence that chromosome 9p21
      genetic variation may constitute a genetic modulator in the cardiovascular system
      in different scenarios. In patients with established CAD, we observed an
      association between the rs2383206 and higher incidence of overall mortality and
      death from cardiac causes in patients with multi-vessel CAD.

PMID- 22856519
TI  - Effect of dietary blueberry pomace on selected metabolic factors associated with
      high fructose feeding in growing Sprague-Dawley rats.
AB  - An experiment was conducted to study the protective effect of feeding extruded
      and unextruded blueberry pomace (BBP) on selected metabolic parameters associated
      with metabolic syndrome in a model of high fructose (HF)-fed growing Sprague
      Dawley rats. Treatments were as follows: (1) control (modified AIN-based diet);
      (2) HF diet (AIN diet with 58% fructose); (3) HF diet with 1.5% unextruded BBP;
      (4) HF diet with 1.5% extruded BBP; (5) HF diet with 3% unextruded BBP; and (6)
      HF diet with 3% extruded BBP. Compared with the control, HF feeding increased
      fasting plasma insulin and fasting and postprandial plasma triglycerides as well
      as homeostatic scores of insulin resistance and beta-cell function, but not
      weight gain, diet intake and efficiency, abdominal fat, oral glucose tolerance,
      and fasting and postprandial plasma glucose, cholesterol, and leptin levels.
      Inclusion of unextruded or extruded BBP was effective in minimizing or
      ameliorating the fructose-induced metabolic anomalies, except postprandial plasma
      triglycerides, especially at 3% of the diet. In addition, unextruded or extruded
      BBP at 3% of the diet was also able to reduce plasma cholesterol and abdominal
      fat relative to the HF control, which may impart additional health benefits.
      Compared with the control, inclusion of unextruded or extruded BBP at both 1.5%
      and 3% resulted in lower total fat weight, and animals fed a diet supplemented
      with 3% unextruded BBP in fasting state or 3% unextruded BBP in fed state had
      lower leptin levels than the control. This is the first study demonstrating the
      beneficial effects of feeding blueberry pomace on health.

PMID- 22856520
TI  - Interferon-gamma, pulmonary macrophages and airway responsiveness in asthma.
AB  - Asthma is increasingly being recognised as involving not only allergic
      inflammatory mechanisms but also a variety of other cell types and cytokines.
      While the role of interferon-gamma(IFN-gamma) in asthma remains controversial, it
      has been proposed to contribute to the pathogenesis of both chronic stable asthma
      and acute severe asthma. We have shown that in a model of chronic allergic asthma
      in mice, airway hyper-responsiveness (AHR) is independent of various Th2
      cytokines and their signalling pathways, but is dependent on IFN-gamma. In a
      model of an allergen-induced acute exacerbation of chronic asthma, we have
      demonstrated that activation of pulmonary macrophages may play a critical role in
      driving the inflammatory response. Furthermore, we have demonstrated that IFN
      gamma stimulation of macrophages can lead to steroidresistant airway inflammation
      and AHR via the production of interleukin-27. These findings strengthen the
      notion that the pathogenesis of the lesions of asthma, and especially of AHR,
      involves both Th2 and Th1 cytokines, as well as interaction between the allergic
      response and the innate host defence system. Targeting the effects of IFN-gamma
      on pulmonary macrophages may be particularly relevant to the treatment of steroid
      resistant acute exacerbations of asthma.

PMID- 22856521
TI  - Investigation of ovarian cancer associated sialylation changes in N-linked
      glycopeptides by quantitative proteomics.
AB  - BACKGROUND: In approximately 80% of patients, ovarian cancer is diagnosed when
      the patient is already in the advanced stages of the disease. CA125 is currently
      used as the marker for ovarian cancer; however, it lacks specificity and
      sensitivity for detecting early stage disease. There is a critical unmet need for
      sensitive and specific routine screening tests for early diagnosis that can
      reduce ovarian cancer lethality by reliably detecting the disease at its earliest
      and treatable stages. RESULTS: In this study, we investigated the N-linked
      sialylated glycopeptides in serum samples from healthy and ovarian cancer
      patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative
      proteomics methods. We identified 45 N-linked sialylated glycopeptides containing
      46 glycosylation sites. Among those, ten sialylated glycopeptides were
      significantly up-regulated in ovarian cancer patients' serum samples. LC-MS/MS
      analysis of the non-glycosylated peptides from the same samples, western blot
      data using lectin enriched glycoproteins of various ovarian cancer type samples,
      and PNGase F (+/-) treatment confirmed the sialylation changes in the ovarian
      cancer samples. CONCLUSION: Herein, we demonstrated that several proteins are
      aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection
      of glycopeptides with abnormal sialylation changes may have the potential to
      serve as biomarkers for ovarian cancer.

PMID- 22856522
TI  - Pepsin immobilized on high-strength hybrid particles for continuous flow online
      digestion at 10,000 psi.
AB  - Pepsin was immobilized on ethyl-bridged hybrid (BEH) particles, and digestion
      performance was evaluated in a completely online format, with the specific intent
      of using the particles for hydrogen-deuterium exchange mass spectrometry (HDX MS)
      experiments. Because the BEH particles are mechanically strong, they could
      withstand prolonged, continuous high-pressure at 10,000 psi. Online digestion was
      performed under isobaric conditions with continuous solvent flow, in contrast to
      other approaches where the pressure or flow is cycled. As expected, digestion
      efficiency at 10,000 psi was increased and reproducibly produced more peptic
      peptides versus digestion at 1000 psi. Prototype columns made with the BEH pepsin
      particles exhibited robust performance, and deuterium back-exchange was similar
      to that of other immobilized pepsin particles. These particles can be easily
      incorporated in existing HDX MS workflows to provide more peptide coverage in
      experiments where fast, efficient, and reproducible online pepsin digestion is
      desired.

PMID- 22856523
TI  - Superhelical DNA as a preferential binding target of 14-3-3gamma protein.
AB  - The 14-3-3 protein family is a highly conserved and widely distributed group of
      proteins consisting of multiple isoforms in eukaryotes. Ubiquitously expressed,
      14-3-3 proteins play key roles in DNA replication, cell cycle regulation, and
      apoptosis. The function of 14-3-3 proteins is mediated by interaction with a
      large number of other proteins and with DNA. It has been demonstrated that 14-3
      3gamma protein binds strongly to cruciform structures and is crucial for
      initiating replication. In this study, we analyzed DNA binding properties of the
      14-3-3gamma isoform to linear and supercoiled DNA. We demonstrate that 14-3
      3gamma protein binds strongly to long DNA targets, as evidenced by
      electrophoretic mobility shift assay on agarose gels. Binding of 14-3-3gamma to
      DNA target results in the appearance of blurry, retarded DNA bands. Competition
      experiments with linear and supercoiled DNA on magnetic beads show very strong
      preference for supercoiled DNA. We also show by confocal microscopy that 14-3-3
      protein in the HCT-116 cell line is co-localized with DNA cruciforms. This
      implies a role for the 14-3-3gamma protein in its binding to local DNA structures
      which are stabilized by DNA supercoiling.

PMID- 22856525
TI  - The importance of modelling the spread of insecticide resistance in a
      heterogeneous environment: the example of adding synergists to bed nets.
AB  - BACKGROUND: Insecticides are an effective and practical tool for reducing malaria
      transmission but the development of resistance to the insecticides can
      potentially compromise controls efforts. In this study a mathematical model was
      developed to explore the effects on mosquito populations of spatial heterogeneous
      deployment of insecticides. This model was used to identify important parameters
      in the evolution of insecticide resistance and to examine the contribution of new
      generation long-lasting insecticidal bed nets, that incorporate a chemical
      synergist on the roof panel, in delaying insecticide resistance. METHODS: A
      genetic model was developed to predict changes in mosquito fitness and resistance
      allele frequency. Parameters describing insecticide selection, fitness cost and
      the additional use of synergist were incorporated. Uncertainty and sensitivity
      analysis were performed followed by investigation of the evolution of resistance
      under scenarios of fully effective or ineffective synergists. RESULTS: The spread
      of resistance was most sensitive to selection coefficients, fitness cost and
      dominance coefficients while mean fitness was most affected by baseline fitness
      levels. Using a synergist delayed the spread of resistance but could, in specific
      circumstances that were thoroughly investigated, actually increase the rate of
      spread. Different spread dynamics were observed, with simulations leading to
      fixation, loss and most interestingly, equilibrium (without explicit
      overdominance) of the resistance allele. CONCLUSIONS: This strategy has the
      potential to delay the spread of resistance but note that in an heterogeneous
      environment it can also lead to the opposite effect, i.e., increasing the rate of
      spread. This clearly emphasizes that selection pressure acting inside the house
      cannot be treated in isolation but must be placed in context of overall
      insecticide use in an heterogeneous environment.

PMID- 22856526
TI  - Effect of coincubation time of sperm-oocytes on fertilization, embryonic
      development, and subsequent pregnancy outcome.
AB  - Several studies have reported improved IVF by shortening the time of sperm-oocyte
      coincubation from 16-18 hours to 1-4 hours. The objective of this study was to
      examine the advantages and disadvantages of a shortened sperm-oocyte coincubation
      time in order to assess the effects of this insemination method for clinical IVF
      practice. Two insemination methods, the shortened method (4 hours) and the
      standard method (16-18 hours) of coincubation of sperm-oocytes for two groups of
      patients based on the quality of sperm were compared. Group I, was composed of
      couples without male factor; Group II, involved couples with mild male factor.
      Fertilization, good quality embryos, clinical pregnancy, and implantation rates
      were compared by two different insemination methods. In Group I, fertilization,
      clinical pregnancy, and implantation rates were not different between the two
      insemination methods. However, the polyspermy rate was significantly higher (P <
      0.05) in the shortened (7.3%) than in the standard (4.1%) insemination method. In
      Group II, the fertilization rate was significantly lower (P < 0.05) using the
      shortened insemination method (62.6%) compared to the standard insemination
      method (68.7%). When fertilization failed with the shortened insemination method,
      the clinical pregnancy and implantation rates were 34.7% and 24.1%, respectively,
      from the rescue intracytoplasmic sperm injection (ICSI). The live birth rate from
      the rescue ICSI was 32.0% with normal infants. The duration of sperm-oocyte
      coincubation does not affect fertilization, embryo quality, clinical pregnancy,
      and implantation rates. However, fertilization rates will decrease with the
      shortened insemination method when the sperm parameters are poor. From the
      results of the present study we suggest that the combination of the shortened
      sperm-oocyte coincubation and rescue ICSI method may be an efficient method for
      IVF treatment in order to prevent fertilization failure when sperm parameters
      were poor as mild male factor.

PMID- 22856527
TI  - Semantic physical science.
AB  - The articles in this special issue arise from a workshop and symposium held in
      January 2012 (Semantic Physical Science'). We invited people who shared our
      vision for the potential of the web to support chemical and related subjects.
      Other than the initial invitations, we have not exercised any control over the
      content of the contributed articles.

PMID- 22856528
TI  - Nature of the interlayer environment in an organoclay optimized for the
      sequestration of dibenzo-p-dioxin.
AB  - A Na-smectite clay (Na-SWy-2) was exchanged with various amounts of
      dimethyldioctadecylammonium bromide (DODA-Br) up to twice the cation exchange
      capacity (CEC). The organoclay (DODA-SWy-2) with DODA-Br added at 2 * CEC
      exhibited a maximum 4.2 nm d-spacing and a 31.4% carbon content, which
      demonstrates DODA(+) intercalation. DODA-SWy-2 was evaluated as an archetype of
      commercial products used to sequester hydrophobic contaminants, and the nature of
      the primarily C18 alkylhydrocarbon-chain interlayer environment was emhasized.
      Shifts in nu(CH) and CH(2) rocking band positions in DODA-SWy-2-complex FTIR
      spectra indicate that DODA C18 chains were more ordered as DODA surface coverage
      was increased. Differential scanning calorimetry analysis indicated a DODA-SWy-2
      gel-to-liquid transition temperature much lower than the melting point of
      crystalline DODA-Br and similar to that of aqueous DODA-Br vesicles. This
      suggests that the transition was governed by C18 alkyl tail-tail interactions in
      the clay interlamellar region. Dibenzo-p-dioxin (DD) sorption from water by DODA
      SWy-2 was compared to DD sorption by the geosorbents granular activated carbon
      (GAC), K-exchanged saponite, and a muck soil. The linear K(l) sorption
      coefficients (log K(l)) from a linear fit of the sorption isotherms were 4.37 for
      DODA-SWy-2, 5.55 for GAC, 3.19 for muck soil, and 2.46 for K-saponite. The DD
      organic-matter-normalized sorption coefficient (K(om)) was ~2.4 times the octanol
      water partition coefficient (K(ow)). This indicates that DD has a higher affinity
      for the nonpolar interlayer DODA organic phase than for octanol. In contrast, the
      K(om) for muck soil DD sorption was ~10 times less than K(ow), which reflects the
      higher polarity of amorphous soil organic matter relative to octanol. Enhanced DD
      uptake by the DODA-derived lipophilic phase in the organoclay is attributed to
      the low polarity, "open" C18 alkyl structure due to the physical dimensions of "v
      shaped" DODA(+) molecular, and low density of the interlamellar phase (~0.50
      g/cm3) density of intercalated DODA(+).

PMID- 22856529
TI  - Group A streptococcal panniculitis.
AB  - Infectious panniculitis caused by group A beta-hemolytic streptococcus is rare,
      especially in immunocompetent patients. Its clinical presentation is usually
      nonspecific, but skin biopsy may provide information on the source. We describe
      the case of a previously healthy 2-year-old girl who presented with fever,
      tachycardia, and diffuse erythematous skin nodule; biopsy revealed a deep lobular
      neutrophilic panniculitis with gram-positive bacteria. 

PMID- 22856530
TI  - In situ electrochemical-transmission surface plasmon resonance spectroscopy for
      poly(pyrrole-3-carboxylic acid) thin-film-based biosensor applications.
AB  - In this study, we describe the combination of transmission surface plasmon
      resonance (TSPR) and electrochemical techniques for the application to biosensors
      with conducting polymers. Electropolymerization was employed to construct
      poly(pyrrole-3-carboxylic acid) (PP3C) film on a gold-coated grating substrate
      using pyrrole-3-carboxylic acid (P3C) monomer solution in 0.5 M H(2)SO(4). In
      situ electrochemical-transmission surface plasmon resonance (EC-TSPR)
      measurements were carried out to study the kinetic and electroactivity properties
      of PP3C film. Immobilization of antihuman IgG on the activated surface and the
      binding process of human IgG and antihuman IgG in neutral solution could be
      detected in situ by EC-TSPR measurement. The surface modification steps on the
      PP3C layer led to an increase in intensity of the transmission peak. The
      performance, sensitivity, and utility of EC-TSPR spectroscopy showed obvious
      advantages for the detection of binding process with the simple experimental
      setup, and could be applied to the study of biomolecular interactions in various
      systems.

PMID- 22856531
TI  - Medicine, morality and health care social media.
AB  - Social media includes many different forms of technology including online forums,
      blogs, microblogs (i.e. Twitter), wikipedias, video blogs, social networks and
      podcasting. The use of social media has grown exponentially and time spent on
      social media sites now represents one in five minutes spent online. Concomitant
      with this online growth, there has been an inverse trajectory in direct face-to
      face patient-provider moments, which continue to become scarcer across the
      spectrum of health care. In contrast to standard forms of engagement and
      education, social media has advantages to include profound reach, immediate
      availability, an archived presence and broad accessibility. Our opportunity as
      health care providers to partner with our patients has never been greater, yet
      all too often we allow risk averse fears to limit our ability to truly leverage
      our good content effectively to the online community. This risk averse behavior
      truly limits our capacity to effectively engage our patients where they are-
      online.

PMID- 22856532
TI  - Biodistribution of inhaled gold nanoparticles in mice and the influence of
      surfactant protein D.
AB  - BACKGROUND: The pulmonary route is very promising for drug delivery by
      inhalation. In this regard, nanoparticulate drug delivery systems are discussed,
      and one very promising nano carrier example is gold nanoparticles (Au NP).
      Directly after their deposition, inhaled Au NP come into contact with pulmonary
      surfactant protein D (SP-D). SP-D can agglomerate Au NP in vitro, and this may
      influence the clearance as well as the systemic translocation in vivo. The aim of
      the present study was to investigate the clearance and translocation of Au NP at
      a very early time point after inhalation, as well as the influence of SP-D.
      METHODS: Aerosolized 20-nm radioactively labeled Au NP were inhaled by healthy
      adult female mice. One group of mice received dissolved 10 MUg of SP-D by
      intratracheal instillation prior to the Au NP inhalation. After a 2-hr Au NP
      inhalation period, the mice were killed immediately, and the clearance and
      translocation to the blood stream were investigated. RESULTS: The highest amount
      of Au NP was associated with the lung tissue. In the bronchoalveolar lavage fluid
      (BALF), more Au NP remained free compared with the amount associated with the
      BALF cells. The amount of Au NP cleared by the mucociliary escalator was low,
      probably because of this very early time point. Instillation of SP-D prior to Au
      NP inhalation had no statistically significant effect on the biodistribution of
      the Au NP. CONCLUSION: Our data show that inhaled Au NP are retained in the mouse
      lungs and are translocated after a short time, and that SP-D has only a minor
      effect on Au NP translocation and clearance at a very early time point.

PMID- 22856533
TI  - Meat supplementation increases arm muscle area in Kenyan schoolchildren.
AB  - The present study examines the effect of animal-source-food (ASF) intake on arm
      muscle area growth as part of a larger study examining causal links between ASF
      intake, growth rate, physical activity, cognitive function and micronutrient
      status in Kenyan schoolchildren. This randomised, controlled feeding intervention
      study was designed with three isoenergetic feeding interventions of meat, milk,
      and plain traditional vegetable stew (githeri), and a control group receiving no
      snack. A total of twelve elementary schools were randomly assigned to
      interventions, with three schools per group, and two cohorts of 518 and 392
      schoolchildren were enrolled 1 year apart. Children in each cohort were given
      feedings at school and studied for three school terms per year over 2 years, a
      total of 9 months per year: cohort I from 1998 to 2000 and cohort II from 1999 to
      2001. Food intake was assessed by 24 h recall every 1-2 months and biochemical
      analysis for micronutrient status conducted annually (in cohort I only).
      Anthropometric measurements included height, weight, triceps skinfold (TSF) and
      mid-upper-arm circumference (MUAC). Mid-upper-arm muscle area (MAMA) and mid
      upper-arm fat area (MAFA) were calculated. The two cohorts were combined for
      analyses. The meat group showed the steepest rates of gain in MUAC and MAMA over
      time, and the milk group showed the next largest significant MUAC and MAMA gain
      compared with the plain githeri and control groups (P< 0.05). The meat group
      showed the least increase in TSF and MAFA of all groups. These findings have
      implications for increasing micronutrient intake and lean body mass in primary
      schoolchildren consuming vegetarian diets.

PMID- 22856534
TI  - Targeting cardiovascular risk: the impact of age, gender and compliance to
      treatment.

PMID- 22856535
TI  - Opioids before and after initiation of pregabalin in patients with diabetic
      peripheral neuropathy.
AB  - OBJECTIVES: To examine opioid prescription claims before and after initiation of
      pregabalin in patients with a diagnosis of diabetic peripheral neuropathy (DPN).
      METHODS: This retrospective analysis used a national commercial database of
      integrated inpatient, outpatient, and prescription claims to identify adults with
      a DPN diagnosis code within 360 days prior to the first claim for pregabalin
      between January 1, 2006 and March 31, 2008. Prescription claims for pregabalin or
      opioids were analyzed in nine consecutive 60-day periods from 180 days before
      through 360 days after the first pregabalin claim. It was not possible to
      establish drug administration dates, compliance rates, indications for opioid
      use, or reasons for treatment discontinuation. RESULTS: Of the 8004 adults who
      met eligibility criteria, 6080 (76%) received an opioid within the 180 days
      before and/or 360 days after their first prescription for pregabalin, including
      3956 (49%) both before and after, 1580 (20%) after only, and 544 (7%) before
      only. The percentage of patients with pregabalin claims covering >=20 of 60 days
      (within 60-day periods) was 99% (day 1-60), 63% (day 61-120), 50% (day 121-180),
      45% (day 181-240), 42% (day 241-300), and 39% (day 301-360). The percentage of
      patients with opioid claims covering >=20 of 60 days within the 60-day periods
      remained stable (range, 25-30%). Among patients with opioid claims, 73-76%
      received only short-acting opioids, 6-7% received only long-acting opioids, and
      18-20% received both short- and long-acting opioids. In the first year, 982 (12%)
      patients had opioid claims covering >=20 of 60 days in every 60-day period (i.e.,
      persistent use of opioids). Coexisting musculoskeletal (95%) or neuropathic (61%)
      pain conditions were frequent. CONCLUSION: A majority of patients with DPN
      receive an opioid before and/or after their first pregabalin claim. Pregabalin
      neither interferes with nor replaces opioid use for pain management in patients
      with DPN. Although nearly 1 in 8 patients received opioids throughout the study
      period, most claims were for short-acting opioids. The majority of this DPN
      sample had other pain conditions, including musculoskeletal and neuropathic pain
      conditions. These results highlight the frequency of opioid use with pregabalin,
      particularly short-acting opioids.

PMID- 22856536
TI  - Genomic characteristics of a diploid F(4) festulolium hybrid (Lolium multiflorum
      * Festuca arundinacea).
AB  - The grass festulolium, a hybrid between the genera  Festuca  and  Lolium , has a
      variety of beneficial agronomic attributes derived from both parents. Compared
      with high-ploidy festulolium, diploid festulolium is well suited to stabilizing
      ploidy and for studying agronomic traits and  genetic relationships. We sought to
      produce a diploid festulolium hybrid that was resistant to summer depression, by
      hybridizing diploid  Lolium multiflorum  Lam. and hexaploid  Festuca arundinacea 
      Schreb., which has a high tolerance to summer depression. We obtained seven
      diploid F(4) plants that were capable of surviving the extremely hot summer in
      Morioka, Japan, in 2010, which was 2.7  degrees C higher than the average summer
      temperature. The observed resistance to summer depression in these plants was
      likely due to heat stress tolerance. The genomic constitutions of these seven
      hybrids were analyzed by GISH, and the chromosomal characteristics of a single
      diploid F(4) was analyzed by FISH using rDNA probes. The results showed that
      although no Festuca-specific genome remained in any of the seven diploid F(4)
      plants, extensive chromosomal rearrangement was observed in one of them. Our
      findings suggested that hybridizing diploid L. multiflorum and hexaploid F.
      arundinacea may be useful for modifying chromosome architecture in the Lolium
      genome with potential applications in chromosome engineering.

PMID- 22856537
TI  - Comparison of the accuracy of aerosol refractive index measurements from single
      particle and ensemble techniques.
AB  - The ability of two techniques, aerosol cavity ring down spectroscopy (A-CRDS) and
      optical tweezers, to retrieve the refractive index of atmospherically relevant
      aerosol was compared through analysis of supersaturated sodium nitrate at a range
      of relative humidities. Accumulation mode particles in the diameter range 300-600
      nm were probed using A-CRDS, with optical tweezer measurements performed on
      coarse mode particles several micrometers in diameter. A correction for doubly
      charged particles was applied in the A-CRDS measurements. Both techniques were
      found to retrieve refractive indices in good agreement with previously published
      results from Tang and Munkelwitz, with a precision of +/-0.0012 for the optical
      tweezers and +/-0.02 for the A-CRDS technique. The coarse mode optical tweezer
      measurements agreed most closely with refractive index predictions made using a
      mass-weighted linear mixing rule. The uncertainty in the refractive index
      retrieved by the A-CRDS technique prevented discrimination between predictions
      using both mass-weighted and volume-weighted linear mixing rules. No
      efflorescence or kinetic limitations on water transport between the particle and
      the gas phase were observed at relative humidities down to 14%. The magnitude of
      the uncertainty in refractive index retrieved using the A-CRDS technique reflects
      the challenges in determining particle optical properties in the accumulation
      mode, where the extinction efficiency varies steeply with particle size.

PMID- 22856538
TI  - Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as
      a potential adjunct to radiation therapy.
AB  - OBJECTIVE: Abdominal and pelvic radiotherapy is limited by the radiosensitivity
      of the small and large intestine. PHY906 (KD018), a state-of-the-art, well
      defined adaptation of a traditional Chinese medicine, decreased intestinal injury
      from chemotherapy in preclinical studies and is in clinical trials with
      chemotherapy. This project assessed whether PHY906 would also reduce intestinal
      injury from abdominal irradiation in mice. MATERIALS AND METHODS: BALB/c mice
      received whole-abdomen irradiation (2 Gy/day) +/- PHY906 by oral gavage twice
      daily for 4 days. Intestinal injury was assayed by physiological observations and
      histological studies. Effects of PHY906 on EMT6 mouse mammary tumors were assayed
      in tumor growth studies. RESULTS: PHY906 decreased toxicity from fractionated
      abdominal irradiation. Radiation alone produced marked blunting and loss of
      villi, crypt hyperplasia and irregular crypt morphology, which were reduced by
      PHY906. The radiation-induced reduction in viable crypt numbers was also
      mitigated by PHY906. PHY906 did not alter radiation-induced weight loss, but
      resulted in more rapid recovery. PHY906 did not alter tumor growth, local
      invasion or metastatic spread and did not protect tumors from growth delays
      produced by single-dose or fractionated irradiation. CONCLUSION: In this mouse
      model, PHY906 (KD018) decreased the toxicity of abdominal irradiation without
      protecting tumors and thereby increased the therapeutic ratio.

PMID- 22856539
TI  - Identifying areas of high risk of human exposure to coccidioidomycosis in Texas
      using serology data from dogs.
AB  - Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis
      affecting humans and animals. Most non-human cases of VF are found in dogs, which
      we hypothesize may serve as sentinels for estimating the human exposure risk. The
      objective of this study is to use the spatial and temporal distribution and
      clusters of dogs seropositive for VF to define the geographic area in Texas where
      VF is endemic, and thus presents a higher risk of exposure to humans. The
      included specimens were seropositive dogs tested at a major diagnostic laboratory
      between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical
      Bayesian estimation to develop an isopleth map of VF seropositive rates using
      kriging. Clusters of seropositive dogs were identified using the spatial scan
      test. Both the isopleth map and the scan test identified an area with a high rate
      of VF-seropositive dogs in the western and southwestern parts of Texas (relative
      risk = 31). This location overlapped an area that was previously identified as a
      potential endemic region based on human surveys. Together, these data suggest
      that dogs may serve as sentinels for estimating the risk of human exposure to VF.

PMID- 22856540
TI  - Medication adherence and utilization in patients with schizophrenia or bipolar
      disorder receiving aripiprazole, quetiapine, or ziprasidone at hospital
      discharge: a retrospective cohort study.
AB  - BACKGROUND: Schizophrenia and bipolar disorder are chronic debilitating disorders
      that are often treated with second-generation antipsychotic agents, such as
      aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized
      for schizophrenia and bipolar disorder often receive these agents at discharge,
      comparatively little information exists on subsequent patterns of
      pharmacotherapy. METHODS: Using a database linking hospital admission records to
      health insurance claims, we identified all patients hospitalized for
      schizophrenia (ICD-9-CM diagnosis code 295.XX) or bipolar disorder (296.0, 296.1,
      296.4-296.89) between January 1, 2001 and September 30, 2008 who received
      aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously
      enrolled for 6 months before and after hospitalization ("pre-admission" and
      "follow-up", respectively) were excluded. We examined patterns of use of these
      agents during follow-up, including adherence with treatment (using medication
      possession ratios [MPRs] and cumulative medication gaps [CMGs]) and therapy
      switching. Analyses were undertaken separately for patients with schizophrenia
      and bipolar disorder, respectively. RESULTS: We identified a total of 43 patients
      with schizophrenia, and 84 patients with bipolar disorder. During the 6-month
      period following hospitalization, patients with schizophrenia received an average
      of 101 therapy-days with the second-generation antipsychotic agent prescribed at
      discharge; for patients with bipolar disorder, the corresponding value was 68
      therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and
      37.3% for those with bipolar disorder; approximately one-quarter of patients
      switched to another agent over this period. CONCLUSIONS: Medication compliance is
      poor in patients with schizophrenia or bipolar disorder who initiate treatment
      with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

PMID- 22856542
TI  - Effects of charge separation, effective concentration, and aggregate formation on
      the phase transfer catalyzed alkylation of phenol.
AB  - The factors that influence the rate of alkylation of phenol under phase transfer
      catalysis (PTC) have been investigated in detail. Six linear, symmetrical
      tetraalkylammonium cations, Me(4)N(+), Et(4)N(+), (n-Pr)(4)N(+), (n-Bu)(4)N(+),
      (n-Hex)(4)N(+), and (n-Oct)(4)N(+), were examined to compare the effects of
      cationic radius and lipophilicity on the rate of alkylation. Tetraalkylammonium
      phenoxide.phenol salts were prepared, and their intrinsic reactivity was
      determined from initial alkylation rates with n-butyl bromide in homogeneous
      solution. The catalytic activity of the same tetraalkylammonium phenoxides was
      determined under PTC conditions (under an extraction mechanism) employing
      quaternary ammonium bromide catalysts. In homogeneous solution the range in
      reactivity was small (6.8-fold) for Me(4)N(+) to (n-Oct)(4)N(+). In contrast,
      under PTC conditions a larger range in reactivity was observed (663-fold). The
      effective concentration of the tetraalkylammonium phenoxides in the organic phase
      was identified as the primary factor influencing catalyst activity. Additionally,
      titration of active phenoxide in the organic phase confirmed the presence of both
      phenol and potassium phenoxide aggregates with (n-Bu)(4)N(+), (n-Hex)(4)N(+), and
      (n-Oct)(4)N(+), each with a unique aggregate stoichiometry. The aggregate
      stoichiometry did not affect the PTC initial alkylation rates.

PMID- 22856541
TI  - Design, synthesis, and preclinical evaluations of novel 4-substituted 1,5
      diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitor
      (NNRTI) drug candidates.
AB  - Twenty-one new 4-substituted diarylaniline compounds (DAANs) (series 13, 14, and
      15) were designed, synthesized, and evaluated against wild-type and drug
      resistant HIV-1 viral strains. As a result, approximately a dozen new DAANs
      showed high potency with low nano- to subnanomolar EC(50) values ranging from 0.2
      to 10 nM. The three most promising compounds 14e, 14h, and 15h exhibited high
      potency against wild-type and drug-resistant viral strains with EC(50) values at
      the subnanomolar level (0.29-0.87 nM) and were comparable to or more potent than
      the new NNRTI drug riplivirine (2) in the same assays. Druglike physicochemical
      property assessments revealed that the most active DAANs (EC(50) < 10 nM) have
      better aqueous solubility (>1-90 MUg/mL at pH 7.4 and pH 2) and metabolic
      stability in vitro than 2, as well as desirable log P values (<5) and polar
      surface areas (PSA) (<140 A(2)). These promising results warrant further
      development of this novel compound class as potential potent anti-AIDS clinical
      trial candidates.

PMID- 22856543
TI  - Is the APLS formula used to calculate weight-for-age applicable to a Trinidadian
      population?
AB  - BACKGROUND: In paediatric emergency medicine, estimation of weight in ill
      children can be performed in a variety of ways. Calculation using the 'APLS'
      formula (weight = [age + 4] * 2) is one very common method. Studies on its
      validity in developed countries suggest that it tends to under-estimate the
      weight of children, potentially leading to errors in drug and fluid
      administration. The formula is not validated in Trinidad and Tobago, where it is
      routinely used to calculate weight in paediatric resuscitation. METHODS: Over a
      six-week period in January 2009, all children one to five years old presenting to
      the Emergency Department were weighed. Their measured weights were compared to
      their estimated weights as calculated using the APLS formula, the Luscombe and
      Owens formula and a "best fit" formula derived (then simplified) from linear
      regression analysis of the measured weights. RESULTS: The APLS formula
      underestimated weight in all age groups with a mean difference of -1.4 kg (95%
      limits of agreement 5.0 to -7.8). The Luscombe and Owens formula was more
      accurate in predicting weight than the APLS formula, with a mean difference of 
      0.4 kg (95% limits of agreement 6.9 to -6.1%). Using linear regression analysis,
      and simplifying the derived equation, the best formula to describe weight and age
      was (weight = [2.5 x age] + 8). The percentage of children whose actual weight
      fell within 10% of the calculated weights using any of the three formulae was not
      significantly different. CONCLUSIONS: The APLS formula slightly underestimates
      the weights of children in Trinidad, although this is less than in similar
      studies in developed countries. Both the Luscombe and Owens formula and the
      formula derived from the results of this study give a better estimate of the
      measured weight of children in Trinidad. However, the accuracy and precision of
      all three formulae were not significantly different from each other. It is
      recommended that the APLS formula should continue to be used to estimate the
      weight of children in resuscitation situations in Trinidad, as it is well known,
      easy to calculate and widely taught in this setting.

PMID- 22856545
TI  - Transcriptional responses of the brain-gonad-liver axis of fathead minnows
      exposed to untreated and ozone-treated oil sands process-affected water.
AB  - Oil sands process-affected water (OSPW) produced by the surface mining oil sands
      industry in Alberta, Canada, is toxic to aquatic organisms. Ozonation of OSPW
      attenuates this toxicity. Altered concentrations of sex steroid hormones,
      impaired reproductive performance, and less prominent secondary sexual
      characteristics have been reported for fish exposed to OSPW. However, the
      mechanism(s) by which these effects occur and whether ozonation can attenuate
      these effects in fish was unknown. The objective of this in vivo study was to
      investigate the endocrine-disrupting effects of OSPW and ozone-treated OSPW on
      the abundances of transcripts of genes in the brain-gonad-liver (BGL) axis in
      male and female fathead minnows (Pimephales promelas). Abundances of transcripts
      of genes important for synthesis of gonadotropins were greater in brains from
      both male and female fish exposed to untreated OSPW compared to that of control
      fish. In gonads from male fish exposed to untreated OSPW the abundances of
      transcripts of gonadotropin receptors and several enzymes of sex hormone
      steroidogenesis were greater than in control fish. The abundances of transcripts
      of estrogen-responsive genes were greater in livers from male fish exposed to
      untreated OSPW than in control fish. In female fish exposed to untreated OSPW
      there was less abundance of transcripts of gonadotropin receptors in gonads, as
      well as less abundance of transcripts of estrogen-responsive genes in livers.
      Many effects were either fully or partially attenuated in fish exposed to ozone
      treated OSPW. The results indicate that (1) OSPW has endocrine-disrupting effects
      at all levels of BGL axis, (2) OSPW has different effects in male and female
      fish, (3) ozonation attenuates the effects of OSPW on abundances of transcripts
      of some genes, and the attenuation is more prominent in males than in females,
      but effects of ozonation on endocrine-disrupting effects of OSPW were less clear
      than in previous in vitro studies. The results provide a mechanistic basis for
      the endocrine-disrupting effects of OSPW from other studies.

PMID- 22856544
TI  - Host co-factors of the retrovirus-like transposon Ty1.
AB  - BACKGROUND: Long-terminal repeat (LTR) retrotransposons have complex modes of
      mobility involving reverse transcription of their RNA genomes in cytoplasmic
      virus-like particles (VLPs) and integration of the cDNA copies into the host
      genome. The limited coding capacity of retrotransposons necessitates an extensive
      reliance on host co-factors; however, it has been challenging to identify co
      factors that are required for endogenous retrotransposon mobility because
      retrotransposition is such a rare event. RESULTS: To circumvent the low frequency
      of Ty1 LTR-retrotransposon mobility in Saccharomyces cerevisiae, we used
      iterative synthetic genetic array (SGA) analysis to isolate host mutations that
      reduce retrotransposition. Query strains that harbor a chromosomal Ty1his3AI
      reporter element and either the rtt101Delta or med1Delta mutation, both of which
      confer a hypertransposition phenotype, were mated to 4,847 haploid ORF deletion
      strains. Retrotransposition was measured in the double mutant progeny, and a set
      of 275 ORF deletions that suppress the hypertransposition phenotypes of both
      rtt101Delta and med1Delta were identified. The corresponding set of 275
      retrotransposition host factors (RHFs) includes 45 previously identified Ty1 or
      Ty3 co-factors. More than half of the RHF genes have statistically robust human
      homologs (E < 1 x 10-10). The level of unintegrated Ty1 cDNA in 181 rhfDelta
      single mutants was altered <2-fold, suggesting that the corresponding co-factors
      stimulate retrotransposition at a step after cDNA synthesis. However, deletion of
      43 RHF genes, including specific ribosomal protein and ribosome biogenesis genes
      and RNA degradation, modification and transport genes resulted in low Ty1 cDNA
      levels. The level of Ty1 Gag but not RNA was reduced in ribosome biogenesis
      mutants bud21Delta, hcr1Delta, loc1Delta, and puf6Delta. CONCLUSION: Ty1
      retrotransposition is dependent on multiple co-factors acting at different steps
      in the replication cycle. Human orthologs of these RHFs are potential, or in a
      few cases, presumptive HIV-1 co-factors in human cells. RHF genes whose absence
      results in decreased Ty1 cDNA include characterized RNA metabolism and
      modification genes, consistent with their having roles in early steps in
      retrotransposition such as expression, nuclear export, translation, localization,
      or packaging of Ty1 RNA. Our results suggest that Bud21, Hcr1, Loc1, and Puf6
      promote efficient synthesis or stability of Ty1 Gag.

PMID- 22856546
TI  - Fabrication of single gold particle arrays with pattern directed electrochemical
      deposition.
AB  - A simple and efficient method for fabricating gold nanoparticle (AuNP) arrays is
      developed. With this method, the AuNP arrays are fabricated by taking an
      electrochemical deposition (ECD) process on the ITO substrate, which is initially
      patterned with nanoimprint lithography (NIL). The stamp for NIL is fabricated by
      the cost-efficient nanosphere lithography (NSL). The size of the AuNPs can be
      adjusted by varying the potential and duration of ECD. In this work, the
      diameters of AuNPs are varied from 130 to 420 nm. The AuNP arrays can be readily
      extended to other conductive substrates, which may be applied for detecting and
      sensing.

PMID- 22856547
TI  - Melatonin MT1 receptor-induced transcriptional up-regulation of p27(Kip1) in
      prostate cancer antiproliferation is mediated via inhibition of constitutively
      active nuclear factor kappa B (NF-kappaB): potential implications on prostate
      cancer chemoprevention and therapy.
AB  - Our laboratory has recently demonstrated a melatonin MT1 receptor-mediated
      antiproliferative signaling mechanism in androgen receptor (AR)-positive prostate
      epithelial cells which involves up-regulation of p27(Kip1) through dual
      activation of Galpha(s)/protein kinase A (PKA) and Galpha(q)/protein kinase C
      (PKC) in parallel, and down-regulation of activated AR signaling via PKC
      stimulation. The aim of the present investigation was to identify the
      transcription factor that mediates melatonin's up-regulatory effect on p27(Kip1)
      in LNCaP and 22Rv1 prostate cancer cells. Deletion mapping and reporter assays of
      the p27(Kip1) promoter revealed that the putative melatonin-responsive
      transcription factor binds to a 116 base-pair region of the promoter sequence,
      which contains a potential nuclear factor kappa B (NF-kappaB) binding site. When
      the NF-kappaB binding site was abolished by site-directed mutagenesis, the
      stimulatory effect of melatonin on p27(Kip1) promoter activity was mitigated.
      Notably, melatonin inhibited the DNA binding of activated NF-kappaB via MT1
      receptor-induced PKA and PKC stimulation. Furthermore, melatonin's up-regulatory
      effect on p27(Kip1) transcription and consequent cell antiproliferation were
      abrogated by NF-kappaB activator but mimicked by NF-kappaB inhibitor. The results
      indicate that inhibition of constitutively active NF-kappaB via melatonin MT1
      receptor-induced dual activation of (Galpha(s)) PKA and (Galpha(q)) PKC can de
      repress the p27(Kip1) promoter leading to transcriptional up-regulation of
      p27(Kip1). MT1 receptor-mediated inhibition of activated NF-kappaB signaling
      provides a novel mechanism supporting the use of melatonin in prostate cancer
      chemoprevention and therapy.

PMID- 22856548
TI  - Embracing change: practical and theoretical considerations for successful
      implementation of technology assisting upper limb training in stroke.
AB  - BACKGROUND: Rehabilitation technology for upper limb training of stroke patients
      may play an important role as therapy tool in future, in order to meet the
      increasing therapy demand. Currently, implementation of this technology in the
      clinic remains low. This study aimed at identifying criteria and conditions that
      people, involved in development of such technology, should take into account to
      achieve a (more) successful implementation of the technology in the clinic.
      METHODS: A literature search was performed in PubMed and IEEE databases, and semi
      structured interviews with therapists in stroke rehabilitation were held, to
      identify criteria and conditions technology should meet to facilitate
      (implementation of) technology-assisted arm-hand skills training in
      rehabilitation therapy of stroke patients. In addition, an implementation
      strategy frequently applied in general health care was used to compose a stepwise
      guidance to facilitate successful implementation of this technology in therapy of
      stroke patients. Implementation-related criteria mentioned by therapists during
      the interviews were integrated in this guidance. RESULTS: Results indicate that,
      related to therapy content, technology should facilitate repetition of task
      related movements, tailored to the patient and patient's goals, in a meaningful
      context. Variability and increasing levels of difficulty in exercises should be
      on offer. Regarding hardware and software design of technology, the system should
      facilitate quick familiarisation and be easily adjustable to individual patients
      during therapy by therapists (and assistants). The system should facilitate
      adaptation to individual patients' needs and their progression over time, should
      be adjustable as to various task-related variables, should be able to provide
      instructions and feedback, and should be able to document patient's progression.
      The implementation process of technology in the clinic is provided as a stepwise
      guidance that consists of five phases therapists have to go through. The guidance
      includes criteria and conditions that motivate therapists, and make it possible
      for them, to actually use technology in their daily clinical practice.
      CONCLUSIONS: The reported requirements are important as guidance for people
      involved in the development of rehabilitation technology for arm-hand therapy of
      stroke patients. The stepwise guide provides a tool for facilitating successful
      implementation of technology in clinical practice, thus meeting future therapy
      demand.

PMID- 22856549
TI  - CYP450 phenotyping and accurate mass identification of metabolites of the 8
      aminoquinoline, anti-malarial drug primaquine.
AB  - BACKGROUND: The 8-aminoquinoline (8AQ) drug primaquine (PQ) is currently the only
      approved drug effective against the persistent liver stage of the hypnozoite
      forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V
      gametocytes of Plasmodium falciparum. To date, several groups have investigated
      the toxicity observed in the 8AQ class, however, exact mechanisms and/or
      metabolic species responsible for PQ's haemotoxic and anti-malarial properties
      are not fully understood. METHODS: In the present study, the metabolism of PQ was
      evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450
      (CYP) and mono-amine oxidase (MAO) families. Based on this information,
      metabolite identification experiments were performed using nominal and accurate
      mass measurements. RESULTS: Relative activity factor (RAF)-weighted intrinsic
      clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4,
      and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism,
      respectively. CYP 2D6 was shown to produce at least six different oxidative
      metabolites along with demethylations, while MAO-A products derived from the PQ
      aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace
      levels of hydroxylated species. CONCLUSIONS: As a result of this work, CYP 2D6
      and MAO-A have been implicated as the key enzymes associated with PQ metabolism,
      and metabolites previously identified as potentially playing a role in efficacy
      and haemolytic toxicity have been attributed to production via CYP 2D6 mediated
      pathways.

PMID- 22856551
TI  - Can LDL-cholesterol targets be achieved in a population at high risk? Results of
      the non-interventional study ACT II.
AB  - OBJECTIVE: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce
      vascular clinical endpoints in outcome studies. Despite this evidence, previous
      cross-sectional analyses reported a mean LDL-C target attainment of <50%. This
      non-interventional, longitudinal study aimed to asses the rate of target
      attainment by intensified LDL-C lowering therapy in a high-risk population under
      routine medical care. DESIGN: This was an open-label, non-interventional,
      observational, non-comparative longitudinal study. METHODS: A total of 1682
      outpatients at high cardiovascular risk, not at LDL-C target despite statin
      therapy, were documented. Treating physicians administered an intensified therapy
      at their discretion. In all, 794 patients completed all the examinations at
      baseline after 3 and 12 months. The achieved LDL-C reductions was evaluated based
      on expert consensus reflecting the 2007 guidelines issued by the European Society
      of Cardiology (ESC) on cardiovascular disease prevention. REGISTRATION:
      www.clinicaltrials.gov , identification number NCT 01381679 RESULTS: In the
      study, 40.3% achieved the individual LDL-C target of <.8 mmol/L (70 mg/dl) or
      <2.5 mmol/L (100 mg/dl); 73% received a simvastatin/ezetimibe fixed-dose
      combination; 3% received add-on ezetimibe and 23% statin therapy at maintained or
      increased doses; 1% received no drug treatment at all. LDL-C declined after 12
      months by -31.0% (ratio 0.69, 95% CI 0.67-0.71, p<0.001), triglycerides by -11.8%
      (ratio 0.88, 95% CI 0.85-0.91, p<0.01) and high-density lipoprotein cholesterol
      (HDL-C) increased by 11.9% (ratio 1.12, 95% CI 1.10-1.14, p<0.01). CONCLUSION:
      Intensified therapy was effective, but target attainment was still low at 40.3%
      or 13.9% with regard to the new 2011 guidelines issued by the European
      Atherosclerosis Society (EAS) and the ESC on dyslipidemias. Enhanced screening of
      LDL-C levels and the use of statins at highest tolerated dose and concomitant
      combination therapy is recommended in order to achieve LDL-C targets outlined by
      current guidelines. Limitations include the design as a non-interventional study.
      However, this study reflects real life conditions.

PMID- 22856552
TI  - Hantavirus infection among wild small mammals in Vellore, south India.
AB  - Wild indigenous small mammals including 83 rodents (bandicoot and black rats, and
      house mice) and a shrew captured from multiple sites in Vellore, south India,
      were tested for serological and molecular evidence of hantavirus infection.
      Indirect immunofluorescence assay (IFA) using Hantaan virus (HTNV) antigen
      indicated hantavirus-reactive antibodies in 16 (19.3%) of 83 rodents (bandicoot
      and black rats). Western blot (WB) using Thailand virus (THAIV) antigen confirmed
      hantavirus-reactive antibodies in nine of the 16 HTNV IFA-positive rodents.
      Reverse transcription polymerase chain reaction (RT-PCR) of lung and kidney
      tissue of captured mammals resulted in the detection of partial S segment
      sequence in a bandicoot rat. This study complements our earlier reports on
      hantavirus epidemiology in south India and documents first laboratory evidence
      for rodent-associated hantaviruses in south India. 

PMID- 22856553
TI  - Delays in seeking cancer diagnosis in relation to beliefs about the curability of
      cancer in patients with different disease locations.
AB  - This study is aimed at investigating factors leading to delayed oncologic
      examinations versus immediate consultation with a physician in patients with
      various cancers. We analysed the results of a study of patients (n = 291)
      reporting for their first oncologic examinations. We conducted structured
      interviews containing social, demographic and clinical data, the Spielberger
      State-Trait Anxiety Inventory, the Beck Depression Inventory and Harris and
      Guten's health appraisal scores. Based on an analysis of decision-making trees,
      the results indicate that it is possible to predict beliefs regarding the
      curability of cancer and immediate versus delayed reporting to a physician.
      Delayed reports may be predicted on the basis of two factors: (1) a belief that
      cancer is incurable combined with increased state anxiety, 'good' or 'very good'
      self-appraisal of health and low depression; and (2) a belief that cancer is
      incurable accompanied by increased anxiety and depression. The characteristics of
      patients delaying a visit to the oncologist suggest the existence of three
      independent factors leading to both considerable (longer than nine months) and
      minor (up to one month) delays in seeking treatment.

PMID- 22856554
TI  - Evaluation of neuropsychological rehabilitation following severe traumatic brain
      injury: a case report.
AB  - This case study presents the evaluation of traumatic brain injury rehabilitation
      for Jane, a 35-year-old woman who sustained a severe traumatic brain injury
      (TBI). On-going rehabilitation addressed difficulties within a structured neuro
      rehabilitative therapeutic milieu and was holistically evaluated. Results showed
      improvement in mood and quality of life and at the compensatory level for
      cognition. At the impairment level, many of the affected areas of cognition
      remained at least below predicted pre-morbid levels. This supports the view that
      although TBI impairments may be permanent, structured neuro-rehabilitation can be
      effective through external and compensatory aids. Recording this holistically
      contributes to evidencing this. 

PMID- 22856555
TI  - Segregation of sperm subpopulations in normozoospermic infertile men.
AB  - Sperm function is essential for fertilization and embryogenesis yet semen contain
      a heterogeneous population of sperm. This study was designed to evaluate two
      different sperm populations separated by the density gradient method. Semen from
      25 idiopathic normozoospermic infertile men was processed by double density
      gradient centrifugation and evaluated for sperm present in the 50% (upper) layer
      and the 90% (lower) layer for reactive oxygen species (ROS), sperm chromatin
      integrity, and morphology. The population of sperm in the 90% layer showed
      significantly lower ROS levels (22.90 (0.92, 85.32) vs. 382.03 (158.30, 1409.51)
      and lower DNA fragmentation index (DFI) (24.26 (22.54, 25.50) vs. 29.93 (28.48,
      31.25) and higher number of sperm with normal morphology (55 (45.0, 60.0) vs.
      32.5 (20, 40) compared to sperm in the 50% layer. However, in the original raw
      semen, sperm DFI (27.02 (26.19, 27.76)) and percentage high DNA stainability (%
      HDS) (3.1 (2.40, 3.78)) cells were significantly higher compared to the 90% layer
      population. Density gradient separation of the sperm subpopulation from the
      original semen favors the selection of sperm with genome integrity, low levels of
      ROS, and normal morphology. Therefore presence of pathological sperm in the semen
      may disrupt the function of normal spermatozoa, and hence the selection of the
      normal sperm subpopulation may be a better candidate for assisted conception.
      Further studies are required to evaluate the gradient separated sperm population
      in assisted reproductive techniques (ART).

PMID- 22856556
TI  - Mental health, duration of unemployment, and coping strategy: a cross-sectional
      study of unemployed migrant workers in eastern China during the economic crisis.
AB  - BACKGROUND: 20 million migrant workers in China lost their jobs during the
      economic crisis of 2008. Both urban migration and unemployment have long been
      documented to be associated with vulnerability to mental problems. This study
      aims to examine the mental health of unemployed migrant workers in Eastern China
      and its relation to duration of unemployment and coping strategy during the
      recent economic crisis. METHODS: The data were collected through interview-based
      survey with a sample of 210 unemployed migrant workers in Zhejiang Province of
      China from 2008 to 2009. Symptom Checklist-90-Revised, Coping Strategies
      Questionnaire, and seven short demographic questions were used. RESULTS: The
      majority of the unemployed migrant workers were found to be young male
      manufacturing industry workers with short-term unemployment and a relatively low
      education level. Nearly 50% of unemployed migrant workers were classified as
      mentally unhealthy and the most frequently reported symptom was depression.
      Compared with the adult norm of 1986, 2003, and 2007 in China, unemployed
      migrants had more mental problems. Long-term unemployed migrant workers had more
      psychiatric symptoms than the short-term unemployed workers and employed migrant
      workers. Unemployed migrant workers with immature coping strategies expressed
      significantly more psychiatric symptoms than those with mixed and mature coping
      strategies. Duration of unemployment and two coping strategies, problem-solving
      and self-blaming, predicted the mental problems of unemployed migrant workers.
      CONCLUSIONS: The results indicated that mental health status of unemployed
      migrant workers in Eastern China was poorer than the national adult norm. More
      psychiatric symptoms are evidenced among unemployed migrant workers who lost
      their jobs for a long term and who had immature coping strategies. These findings
      can be used for prevention and intervention of mental illness among unemployed
      migrant workers.

PMID- 22856557
TI  - Lung physiology and aerosol deposition imaged with positron emission tomography.
AB  - Physiological conditions and pathophysiological changes in the lungs may affect
      many applications in aerosol medicine and pulmonary drug delivery. In the
      diseased lung, spatial heterogeneity in function and structure may cause
      substantial changes in aerosol transport and local deposition among different
      lung regions. Non-uniform aerosol deposition affects airway or tissue
      pharmacological dosing, which could reduce the therapeutic effectiveness of
      inhalation therapy. This review article presents examples of pulmonary imaging
      using PET and PET-CT in lung physiology with an emphasis on their implications
      for aerosol medicine. Measurements of regional ventilation, perfusion, and
      ventilation/perfusion ratio, by imaging local kinetics of intravenously injected
      Nitrogen-13 in saline solution, and of pulmonary inflammation, by assessing the
      regional uptake of the radiotracer (18)F-FDG, are presented. These examples
      demonstrate that it is possible to access both preexisting conditions, such as
      heterogeneity of ventilation, perfusion, and/or inflammatory stimuli, which may
      affect inhalation therapy, and the functional effects of inhaled medications or
      inflammatory agents on lung regional function. The imaging techniques described
      could be efficient tools to evaluate quantitatively and noninvasively these
      processes in vivo. Furthermore, it can be expected that imaging of respiratory
      structure and function will yield sensitive biomarkers of disease, which will
      help and speed drug discovery, and the evaluation of novel inhalation therapies.

PMID- 22856559
TI  - Inactivation of salmonella on tomato stem scars by edible chitosan and organic
      Acid coatings.
AB  - This study was conducted to investigate the efficacy of antimicrobial coatings
      for inactivation of Salmonella on the surface of tomato stem scars. Scars were
      inoculated with a four-strain cocktail of Salmonella (serovars Montevideo,
      Newport, Saintpaul, and Typhimurium)  and coated with acid-chitosan solutions.
      The chitosan coating with three acids (3A plus chitosan), the chitosan coating
      with one acid, and the three-acid solution without chitosan reduced the
      populations of Salmonella by 6.0, 3.6, and 5.3 log CFU per stem scar,
      respectively. Addition  of allyl isothiocyanate (10 MUl/ml) to the 3A plus
      chitosan coating did not significantly increase (P > 0.05) the antimicrobial
      efficacy. Although the populations of Salmonella in the controls (ca. 7.5 log CFU
      per stem scar) did not change significantly throughout the 14-day  storage period
      at 10 degrees  C, Salmonella cells were reduced to undetectable levels (< 0.7 log
      CFU per stem scar) in the samples treated with 3A plus chitosan coating after two
      days of storage, and no growth was observed for the remaining storage period.
      Results from this study demonstrate  that coatings of acid plus chitosan provide
      an alternative antimicrobial intervention for decontamination of tomatoes.

PMID- 22856558
TI  - Aptamer-containing surfaces for selective capture of CD4 expressing cells.
AB  - Aptamers have recently emerged as an excellent alternative to antibodies because
      of their inherent stability and ease of modification. In this paper, we describe
      the development of an aptamer-based surface for capture of cells expressing CD4
      antigen. The glass or silicon surfaces were modified with amine-terminated
      silanes and then modified with thiolated RNA aptamer against CD4. Modification of
      the surface was first characterized by ellipsometry to demonstrate assembly of
      biointerface components and to show specific capture of recombinant CD4 protein.
      Subsequently, surfaces were challenged with model lymphocytes (cell lines) that
      were either positive or negative for CD4 antigen. Our experiments show that
      aptamer-functionalized surfaces have similar capture efficiency to substrates
      containing anti-CD4 antibody. To mimick capture of specific T-cells from a
      complex cell mixture, aptamer-modified surfaces were exposed to binary mixtures
      containing Molt-3 cells (CD4+) spiked into Daudi B cells (CD4-). 94% purity of
      CD4 cells was observed on aptamer-containing surfaces from an initial fraction of
      15% of CD4. Given the importance of CD4 cell enumeration in HIV/AIDS diagnosis
      and monitoring, aptamer-based devices may offer an opportunity for novel cell
      detection strategies and may yield more robust and less expensive blood analysis
      devices in the future.

PMID- 22856560
TI  - Novel real-time PCR method to detect Escherichia coli O157:H7 in raw milk cheese
      and raw ground meat.
AB  - Raw milk, raw milk cheeses, and raw ground meat have been implicated in
      Escherichia coli O157:H7 outbreaks. Developing methods to detect these bacteria
      in raw milk and meat products is a major challenge for food safety. The aim of
      our study was to develop a real-time PCR assay  to detect E. coli O157:H7 in raw
      milk cheeses and raw ground meat. Well-known primers targeting a mutation at
      position +93 of the uidA gene in E. coli O157:H7 were chosen, and a specific
      TaqMan-minor groove binder probe was designed. This probe targets another
      mutation,  at position +191 of the uidA gene in E. coli O157:H7. The first step
      in the study was to evaluate the specificity of this probe with 156 different
      O157:H7/NM strains and 48 non-O157:H7/NM strains of E. coli. The sensitivity of
      the method was evaluated by pre- and postinoculation  of cheeses and meat
      enrichments with different E. coli O157:H7 strains. All the E. coli O157:H7
      isolates tested were positive, and none of the other bacteria were detected. Our
      results indicate that this method is sensitive enough to detect 10(2) E. coli
      O157:H7  isolates per ml of cheese or meat enrichment broth (24 h at 41.5 degrees
      C) and is more sensitive than the International Organization for Standardization
      reference method. We can conclude that this new real-time PCR protocol is a
      useful tool for rapid, specific, and sensitive detection of E.  coli O157:H7 in
      raw milk and raw ground meat products.

PMID- 22856561
TI  - Detection and enumeration of four foodborne pathogens in raw commingled silo milk
      in the United States.
AB  - A nationwide survey was conducted to obtain qualitative and quantitative data on
      bacterial contamination of raw commingled silo milk intended for pasteurization.
      The levels of total aerobic bacteria, total coliforms, Enterobacteriaceae,
      Escherichia coli, and Staphylococcus  aureus were determined using the TEMPO
      system. The prevalence rates and levels of presumptive Bacillus cereus, E. coli
      O157:H7, Listeria monocytogenes, and Salmonella spp. were determined in 214
      samples. B. cereus was detected in 8.91% of samples, at 3.0 to  93 CFU/ml. E.
      coli O157:H7 was detected in 3.79 to 9.05% of samples, at <0.0055 to 1.1 CFU/ml,
      depending on the assay utilized. Salmonella spp. were recovered from 21.96 to
      57.94% of samples, at <0.0055 to 60 CFU/ml. L. monocytogenes was detected in
      50.00% of samples,  at <0.0055 to 30 CFU/ml. The average log-transformed counts
      of total viable bacteria were slightly lower in samples containing no pathogens.
      No correlation was observed between the levels of organisms detected with the
      TEMPO system and the presence or levels of any pathogen except E.  coli O157:H7.
      A higher average log-transformed count of total viable bacteria was observed in
      samples positive for this organism. The high prevalence rates of target pathogens
      may be attributed to a variety of factors, including detection methods, sample
      size, and commingling of the milk  in the silo. The effects of commingling likely
      contributed to the high prevalence rates and low levels of target pathogens
      because of the inclusion of milk from multiple bulk tanks. The high prevalence
      rates also may be the result of analysis of larger sample volumes using more
      sensitive detection  methods. These quantitative data could be utilized to
      perform more accurate risk assessments and to better estimate the appropriate
      level of protection for dairy products and processing technologies.

PMID- 22856562
TI  - Survival of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes on
      inoculated almonds and pistachios stored at -19, 4, and 24 degrees  C.
AB  - The survival of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes
      was determined on almonds and pistachios held at typical storage temperatures.
      Almond kernels and inshell pistachios were inoculated with four- to six-strain
      cocktails of nalidixic acid-resistant  Salmonella, E. coli O157:H7, or L.
      monocytogenes at 6 log CFU/g and then dried for 72 h. After drying, inoculated
      nuts were stored at -19, 4, or 24 degrees C for up to 12 months. During the
      initial drying period after inoculation, levels of all pathogens declined by 1 to
      -log  CFU/g on both almonds and pistachios. During storage, moisture content
      (4.8%) and water activity (0.4) of the almonds and pistachios were consistent at 
      19 degrees C; increased slowly to 6% and 0.6, respectively, at 4 degrees C; and
      fluctuated from 4 to 5% and 0.3 to 0.5 at 24 degrees C, respectively.  Every 1 or
      2 months, levels of each pathogen were enumerated by plating; samples were
      enriched when levels fell below the limit of detection. No reduction in
      population level was observed at -19 or 4 degrees C for either pathogen, with the
      exception of E. coli O157:H7-inoculated  almonds stored at 4 degrees C (decline
      of 0.09 log CFU/g/month). At 24 degrees C, initial rates of decline were 0.20,
      0.60, and 0.71 log CFU/g/month on almonds and 0.15, 0.35, and 0.86 log
      CFU/g/month on pistachios for Salmonella, E. coli O157:H7, and L. monocytogenes,
      respectively,  but distinct tailing of the survival curves was noted for both E.
      coli O157:H7 and L. monocytogenes.

PMID- 22856563
TI  - Effects of lactic acid on the growth characteristics of Listeria monocytogenes on
      cooked ham surfaces.
AB  - The surfaces of ready-to-eat meats are susceptible to postprocessing
      contamination by Listeria monocytogenes. This study examined and modeled the
      growth characteristics of L. monocytogenes on cooked ham treated with lactic acid
      solutions (LA). Cooked ham was inoculated  with L. monocytogenes (ca. 10(3)
      CFU/g), immersed in 0, 0.5, 0.75, 1.0, 1.25, 1.5, and 2.0% LA for 30 min, vacuum
      packaged, and stored at 4, 8, 12, and 16 degrees C. LA immersion resulted in <0.7
      log CFU/g immediate reduction of L. monocytogenes on ham surfaces, indicating 
      the immersion alone was not sufficient for reducing L. monocytogenes. During
      storage, no growth of L. monocytogenes occurred on ham treated with 1.5% LA at 4
      and 8 degrees C and with 2% LA at all storage temperatures. LA treatments
      extended the lag-phase duration (LPD) of L. monocytogenes  and reduced the growth
      rate (GR) from 0.21 log CFU/day in untreated ham to 0.13 to 0.06 log CFU/day on
      ham treated with 0.5 to 1.25% LA at 4 degrees C, whereas the GR was reduced from
      0.57 log CFU/day to 0.40 to 0.12 log CFU/day at 8 degrees C. A significant
      extension of the LPD and reduction of the  GR of L. monocytogenes occurred on ham
      treated with >1.25% LA. The LPD and GR as a function of LA concentration and
      storage temperature can be satisfactorily described by a polynomial or expanded
      square-root model. Results from this study indicate that immersion treatments
      with >1.5%  LA for 30 min may be used to control the growth of L. monocytogenes
      on cooked meat, and the models would be useful for selecting LA immersion
      treatments for meat products to achieve desired product safety.

PMID- 22856564
TI  - Evaluation of methods to assess the biofilm-forming ability of Listeria
      monocytogenes.
AB  - The contamination of ready-to-eat products with Listeria monocytogenes has been
      related to the presence of biofilms in production lines, as biofilms protect
      cells from chemical sanitizers. The ability of L. monocytogenes to produce
      biofilms is often evaluated using in  vitro methodologies. This work aims to
      compare the most frequently used methodologies, including high-throughput
      screening methods based on microplates (crystal violet and the Calgary Biofilm
      Device) and methods based on CFU enumeration and microscopy after growth on
      stainless steel. Thirty  isolates with diverse origins and genetic
      characteristics were evaluated. No (or low) correlations between methods were
      observed. The only significant correlation was found between the methods using
      stainless steel. No statistically significant correlation (P > 0.05) was detected
      among genetic lineage, serovar, and biofilm-forming ability. Because results
      indicate that biofilm formation is influenced by the surface material, the
      extrapolation of results from high-throughput methods using microplates to more
      industrially relevant surfaces should be undertaken with caution.

PMID- 22856565
TI  - Biofilm formation by Shiga toxin-producing Escherichia coli O157:H7 and Non-O157
      strains and their tolerance to sanitizers commonly used in the food processing
      environment.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains are important foodborne
      pathogens. Among these, E. coli O157:H7 is the most frequently isolated STEC
      serotype responsible for foodborne diseases. However, the non-O157 serotypes have
      been associated with serious  outbreaks and sporadic diseases as well. It has
      been shown that various STEC serotypes are capable of forming biofilms on
      different food or food contact surfaces that, when detached, may lead to cross
      contamination. Bacterial cells at biofilm stage also are more tolerant to
      sanitizers compared  with their planktonic counterparts, which makes STEC
      biofilms a serious food safety concern. In the present study, we evaluated the
      potency of biofilm formation by a variety of STEC strains from serotypes O157:H7,
      O26:H11, and O111:H8; we also compared biofilm tolerance with two types of common
      sanitizers, a quaternary ammonium chloride-based sanitizer and chlorine. Our
      results demonstrated that biofilm formation by various STEC serotypes on a
      polystyrene surface was highly strain-dependent, whereas the two non-O157
      serotypes showed a higher potency of pellicle formation at  air-liquid interfaces
      on a glass surface compared with serotype O157:H7. Significant reductions of
      viable biofilm cells were achieved with sanitizer treatments. STEC biofilm
      tolerance to sanitization was strain-dependent regardless of the serotypes. Curli
      expression appeared to play a critical  role in STEC biofilm formation and
      tolerance to sanitizers. Our data indicated that multiple factors, including
      bacterial serotype and strain, surface materials, and other environmental
      conditions, could significantly affect STEC biofilm formation. The high potential
      for biofilm formation  by various STEC serotypes, especially the strong potency
      of pellicle formation by the curli-positive non-O157 strains with high
      sanitization tolerance, might contribute to bacterial colonization on food
      contact surfaces, which may result in downstream product contamination.

PMID- 22856566
TI  - Role of lactic acid bacteria as a biosanitizer to prevent attachment of Listeria
      monocytogenes F6900 on deli slicer contact surfaces.
AB  - The study was conducted to evaluate the attachment of three lactic acid bacteria
      (LAB) strains and their combination in a cocktail, to stainless steel coupons
      from a deli slicer, and their ability to inhibit the attachment of Listeria
      monocytogenes. In a previous study, three  LAB strains, Pediococcus acidilactici,
      Lactobacillus amylovorus, and Lactobacillus animalis, were isolated from ready-to
      eat meat and exhibited antilisterial effect. In the study reported here,
      hydrophobicity tests were determined according to the method of microbial
      adhesion  to solvent. The attachment of the cells was evaluated on stainless
      steel coupons from deli slicers. Extracellular carbohydrates were determined with
      a colorimetric method. Based on these tests, L. animalis exhibited the greatest
      hydrophobicity (26.3%), and its adherence increased sharply  from 24 to 72 h,
      whereas L. amylovorus yielded the lowest hydrophobicity (3.86%) and was weakly
      adherent. Although P. acidilactici had moderate hydrophobicity (10.1%), it
      adhered strongly. The attached LAB strains produced significantly (P < 0.05)
      higher total carbohydrates  than their planktonic counterparts did, which is an
      important characteristic for attachment. Three conditions were simulated to
      evaluate the ability of the LAB cocktail (10(8) CFU/ml) to competitively exclude
      L. monocytogenes (10(3) CFU/ml) on the surface of the coupons.  The coupons were
      pretreated with the LAB cocktail for 24 h prior to the addition of L.
      monocytogenes, simultaneously treated with the LAB cocktail and L. monocytogenes,
      or pretreated with L. monocytogenes 24 h prior to the addition of the LAB
      cocktail. The LAB cocktail  was able to reduce the attachment L. monocytogenes
      significantly (P < 0.05). The LAB cocktail indicated potential attachment on
      stainless steel and bacteriostatic activity toward L. monocytogenes attached on
      stainless steel, which indicates a possible role for LAB as  a biosanitizer in
      the food industry.

PMID- 22856567
TI  - Human norovirus transfer to stainless steel and small fruits during handling.
AB  - Human noroviruses (NoVs) cause an estimated 58% of foodborne illnesses in the
      United States annually. The majority of these outbreaks are due to contamination
      by food handlers. The objective of this study was to quantify the transfer rate
      and degree of contamination that occurs on small  fruits (blueberries, grapes,
      and raspberries) and food contact surfaces (stainless steel) when manipulated
      with NoV-contaminated hands. Human NoVs (genogroups I and II [GI and GII]) and
      murine norovirus (MNV-1) were inoculated individually or as a three-virus
      cocktail onto donor surfaces (gloved  fingertips or stainless steel) and either
      immediately interfaced with one or more recipient surfaces (fruit, gloves, or
      stainless steel) or allowed to dry before contact. Viruses on recipient surfaces
      were quantified by real-time quantitative reverse transcriptase PCR. Transfer
      rates were  58 to 60% for GII NoV from fingertips to stainless steel,
      blueberries, and grapes and 4% for raspberries under wet conditions. Dry transfer
      occurred at a much lower rate (<1%) for all recipient surfaces. Transfer rates
      ranged from 20 to 70% from fingertips to stainless steel or fruits for  the GI,
      GII, and MNV-1 virus cocktail under wet conditions and from 4 to 12% for all
      viruses under dry transfer conditions. Fomite transfer (from stainless steel to
      fingertip and then to fruit) was lower for all viruses, ranging from 1 to 50% for
      wet transfer and 2 to 11% for dry transfer.  Viruses transferred at higher rates
      under wet conditions than under dry conditions. The inoculum matrix affected the
      rate of virus transfer, but the majority of experiments resulted in no difference
      in the transfer rates for the three viruses. While transfer rates were often low,
      the amount  of virus transferred to recipient surfaces often exceeded 4- or 5-log
      genomic copy numbers, indicating a potential food safety hazard. Quantitative
      data such as these are needed to model scenarios of produce contamination by food
      handling and devise appropriate interventions to manage risk.

PMID- 22856568
TI  - Multilocus genetic characterization of two ant vectors (Group II "Dirty 22"
      species) known to contaminate food and food products and spread foodborne
      pathogens.
AB  - The U.S. Food and Drug Administration utilizes the presence of filth and
      extraneous materials as one of the criteria for implementing regulatory actions
      and assessing adulteration of food products of public health importance. Twenty
      two prevalent pest species (also known as the ''Dirty  22'' species) have been
      considered by this agency as possible vehicles for the spread of foodborne
      diseases, and the presence of these species is considered an indicator of
      unsanitary conditions in food processing and storage facilities. In a previous
      study, we further categorized the Dirty  22 species into four groups: group I
      includes four cockroach species, group II includes two ant species, group III
      includes 12 fly species, and group IV includes four rodent species. Here, we
      describe the development of three nested PCR primer sets and multilocus genetic
      characterization by  amplifying the small subunit rRNA, elongation factor 1
      alpha, and wingless (WNT-1) genes of group II Dirty 22 ant species Monomorium
      pharaonis and Solenopsis molesta. These novel group II Dirty 22 species-specific
      nested PCR primer sets can be used when the specimens cannot be  identified using
      conventional microscopic methods. These newly developed assays will provide
      correct identification of group II Dirty 22 ant species, and the information can
      be used in the control of foodborne pathogens.

PMID- 22856569
TI  - Safe Eats: an evaluation of the use of social media for food safety education.
AB  - Many undergraduate students are cooking for the first time, and they need to
      learn safe food practices to reduce their risk of foodborne illness. Social media
      tools are being utilized to disseminate public health messages, but limited
      research has been conducted to examine the effectiveness  of these tools for food
      safety education. The purpose of this study was to develop and evaluate a social
      media-based intervention for young adults to improve food safety attitudes,
      practices, and knowledge. Preliminary surveys were conducted and online focus
      groups were convened to guide  design of this social media intervention. College
      students (710) were included in treatment and control groups. Results from
      pretests and posttests indicate that participation in the "Safe Eats" Facebook
      intervention leads to improvements in food safety attitudes, practices, and 
      knowledge. Although students reported that they learned more from the
      intervention than from a traditional lecture, the combination of lecture and
      Facebook resulted in higher knowledge scores than those resulting from the
      intervention alone. Participants who spent more time on the Facebook  page had
      greater improvements in food safety attitudes and practices.

PMID- 22856570
TI  - Tracking the sources of salmonella in ground beef produced from nonfed cattle.
AB  - The objective of this study was to determine the source(s) of Salmonella
      contamination in ground beef. One hundred dairy cows were harvested in a U.S.
      commercial beef processing plant. Samples of hides, carcasses after hide removal
      and before exposure to antimicrobial intervention,  carcasses after all
      antimicrobial interventions, superficial cervical lymph nodes from the chuck,
      trim, ground beef, and air were obtained. Ninety-six percent of the hide samples,
      47% of the carcasses before intervention, 18% of the lymph nodes, 7.14% of the
      trim, and 1.67% of the ground beef  samples were positive for Salmonella. None of
      the samples obtained from the carcasses after the full complement of
      interventions and none of the air samples were positive for Salmonella. All
      Salmonella-positive samples were subjected to pulsed-field gel electrophoresis, 
      and eight DNA Xba I restriction patterns were identified. The majority of
      isolates had one of two restriction digest patterns. The strain isolated from
      ground beef had the same pattern as the strains isolated from hides and from
      carcasses immediately after hide removal. The Salmonella  isolates from trim
      samples and lymph nodes also had the same restriction digest pattern. These
      results indicate that hide and lymph nodes are the most likely sources of
      Salmonella in ground beef. Dressing practices that effectively reduce or
      eliminate the transfer of bacteria from hide  to carcass and elimination of lymph
      nodes as a component of raw ground beef should be considered as measures to
      reduce Salmonella contamination of ground beef. Because total elimination of
      lymph nodes from ground beef is not possible, other approaches should be
      explored. Easily accessible  lymph nodes could be screened for Salmonella very
      early in the slaughter process. When the results are positive for Salmonella, the
      corresponding carcasses should be fabricated separately at the end of the
      production run, and the trim from these carcasses should be subjected  to a
      treatment that destroys Salmonella.

PMID- 22856571
TI  - Prevalence of Salmonella on retail chicken meat in Russian Federation.
AB  - The objective of this study was to estimate the prevalence of Salmonella on raw
      retail chicken meat in Russia. Broiler chicken carcasses (n = 698) were collected
      from three regions of Russia: central (i.e., Moscow area), northwest (i.e., St.
      Petersburg area), and southern  (i.e., Krasnodar area). In each region, samples
      were collected to represent various cities and districts, as well as different
      types of retail stores and carcass storage temperatures (i.e., chilled and
      frozen). All chicken samples were analyzed for the presence of Salmonella using a
      whole-carcass rinse method. The overall Salmonella prevalence was 31.5%. There
      were significant differences (P < 0.05) in Salmonella prevalence by (i) region
      29.3% (n = 464) in Moscow, 38.5% (n = 192) in St. Petersburg, and 23.8% (n = 42) 
      in Krasnodar; (ii) retail store type-28.8% (n = 236) in hypermarkets, 31.9% (n =
      260) in supermarkets (part of chain stores), 44.3% (n = 61) in independent
      supermarkets, 42.9% (n = 28) in independent minimarkets, and 26.6% (n = 113) in
      wet markets;  and (iii) poultry company-34.3% (n = 545) on chickens produced by
      integrated companies compared with 22.9% (n = 118) on chickens produced by
      nonintegrated companies. Strategies such as good agriculture and management
      practices should be enhanced to reduce Salmonella  prevalence on raw poultry in
      Russia and therefore increase the safety of chicken products.

PMID- 22856572
TI  - Prevalence and distribution of Arcobacter spp. in raw milk and retail raw beef.
AB  - A total of 106 beef samples which consisted of local (n = 59) and imported (n =
      47) beef and 180 milk samples from cows (n = 86) and goats (n = 94) were
      collected from Selangor, Malaysia. Overall, 30.2% (32 of 106) of beef samples
      were found positive for  Arcobacter species. Imported beef was significantly more
      contaminated (46.80%) than local beef (16.9%). Arcobacter butzleri was the
      species isolated most frequently from imported (81.8%) and local (60%) beef,
      followed by Arcobacter cryaerophilus in local (33.3%) and imported  (18.2%) beef
      samples. Only one local beef sample (10%) yielded Arcobacter skirrowii.
      Arcobacter species were detected from cow's milk (5.8%), with A. butzleri as the
      dominant species (60%), followed by A. cryaerophilus (40%), whereas none of the
      goat's milk samples  were found positive for Arcobacter. This is the first report
      of the detection of Arcobacter in milk and beef in Malaysia.

PMID- 22856573
TI  - Prevalence and concentration of Arcobacter spp. on Australian Beef Carcasses.
AB  - The International Commission on Microbiological Specifications for Foods (ICMSF)
      classified Arcobacter spp. as emerging pathogens in 2002. Arcobacter spp. have
      been isolated from numerous food products at retail and from animal carcasses and
      feces at slaughter. A survey was conducted to determine both the prevalence and
      concentration of Arcobacter spp. on pre-chill beef carcasses. Surface swab
      samples were collected from 130 beef carcasses at the end of processing, prior to
      chilling. The concentration of Arcobacter spp. was determined by a most-probable
      number per square centimeter (3 by 3) method with a limit of detection of 0.12
      CFU/cm(2). Of the 100 carcasses examined from export abattoirs, 20 (20.0%) were
      contaminated with Arcobacter spp., and 5 of these had quantifiable levels of
      contamination ranging from 0.12 to 0.31 CFU/cm(2). Of the 30 carcasses examined
      at a pet food abattoir, 25 (83.3%) were contaminated with Arcobacter spp., and 10
      of these had quantifiable levels of contamination ranging from 0.12 to 0.95
      CFU/cm(2). Three species of Arcobacter, A. butzleri, A. cryaerophilus, and A.
      skirowii, were identified by PCR. Each of the species was present in an
      approximately equal ratio from export abattoirs. This study demonstrates that
      slaughter practices at export abattoirs are sufficient to maintain both low
      prevalence and low levels of contamination of beef carcasses with Arcobacter spp.

PMID- 22856574
TI  - Seroprevalence of anti-hepatitis E virus and anti-Salmonella antibodies in pigs
      at slaughter in Switzerland.
AB  - Hepatitis E virus (HEV) and Salmonella bacteria are zoonotic pathogens that can
      be acquired by foodborne transmission because food animals, for example pigs, are
      recognized as a reservoir. The objectives of this study were to determine the
      seroprevalence of anti-HEV immunoglobulin  G (IgG) and anti-Salmonella antibodies
      from healthy pigs at slaughter in Switzerland, a country with a good health
      status of pig herds (e.g., eradication of enzootic pneumonia) compared with those
      of many countries in the European Union, and a rate of importation of live pigs
      that is  very low (<1%). Based on pooled (diaphragm muscles from 3 to 5 animals
      per producer) meat juice samples, 120 (60%) of 200 and 8 (4%) of 200 samples were
      positive for anti-HEV IgG and anti-Salmonella antibodies, respectively. HEV seems
      to be highly prevalent among fattening pigs in  Switzerland, whereas the low
      seroprevalence of anti-Salmonella IgG has not changed in recent years.

PMID- 22856575
TI  - Characterization of antimicrobial resistance and virulence genotypes of
      Enterococcus faecalis recovered from a pork processing plant.
AB  - The objective of this study was to assess the antimicrobial resistance and
      virulence genotypes of Enterococcus faecalis isolated from samples obtained from
      a commercial pork processing plant. A total of 200 samples were randomly obtained
      from carcasses after bleeding (BC; 50  samples) and pasteurization (PC; 100
      samples) and from retail pork products (RP; 50 samples). One isolate from each E.
      faecalis -positive sample was analyzed for antimicrobial susceptibility and
      characterized using a enterococcal microarray for analysis of resistance and
      virulence  genes. E. faecalis was isolated from 79.5% of BC samples, 2% of PC
      samples, and 72.7% of RP samples. Resistance to the clinically important drugs
      ciprofloxacin (one isolate each from BC and RP samples) and daptomycin (one
      isolate each from PC and RP samples) was found. Multiresistance  (to five or more
      antimicrobials) was more common in E. faecalis isolates from BC (77.4% of
      isolates) samples than those from PC (25%) and RP (37.6%) samples. Resistance to
      kanamycin (43.5%) and streptomycin (69.2%) was noted mostly in E. faecalis from
      BC samples. The most common  resistance genes (>5% prevalence) found in E.
      faecalis were those for aminoglycosides (aac(6), aphA3, and aadE), macrolides
      lincosamide (ermB, ermA, sat(4), and linB), and tetracyclines (tetL, tetM, and
      tetO ). The virulence genes expressing  adhesion (ace, efaAfs, and agrBfs),
      gelatinase (gelE), and pheromone (cAM, ccF10, cob, and cpd1) factors were found
      in the majority of isolates. Significant associations were found between
      resistance and virulence genes, suggesting their possible relationship.  These
      data suggest that carcasses entering the final product processing area are mostly
      free of E. faecalis but are recontaminated with antimicrobial-resistant strains
      during processing. The source of these contaminants remains to be identified;
      however, these results underscore the  importance of E. faecalis as a reservoir
      of resistance and virulence genes.

PMID- 22856576
TI  - Assessment of F-RNA coliphage as a potential indicator of enteric virus
      contamination of hog carcasses.
AB  - Hepatitis E virus (HEV) is common in pigs, and some swine HEV strains are closely
      related to human strains. The zoonotic transmission of HEV is now well
      established. HEV can be detected by molecular techniques, but the significance of
      the presence of viral nucleic acid is questionable  when foods are subjected to
      virus inactivation treatments. F-RNA coliphages are attractive candidates as
      indicators for enteric viruses because they are similar in size and survival
      characteristics and can be rapidly cultured. Information on the contamination of
      hog carcasses with enteric  or hepatic viruses during slaughter is lacking. The
      objective of this study was to compare the incidence and levels of contamination
      of hog carcasses with F-RNA coliphages, HEV, total aerobic bacteria, coliforms,
      and Escherichia coli at different stages of the dressing process. Hog  carcasses
      entering the commercial slaughter facility are heavily contaminated with F-RNA
      coliphages and HEV. Subsequent processes such as scalding, singing, and
      pasteurization can reduce the incidence and levels of F-RNA coliphages and HEV
      substantially to almost undetectable levels. Large  discrepancies between the
      amount of viral nucleic acid and infectious F-RNA coliphage particles, both at
      high levels and low levels of contamination, were observed. The prevalence and
      levels of viable F-RNA coliphages were lower than those of total aerobic
      bacteria, coliforms, and E. coli  in the anal area and on random sites before
      pasteurization. At a research abattoir, there was no overall mean reduction of
      viable F-RNA coliphages recovered from random sites before pasteurization and
      after washing, whereas overall mean reductions of 1.2, 2.6, and 2.9 log CFU for
      total aerobic  bacteria, coliforms, and E. coli, respectively, were obtained.
      These findings suggest that bacteria such as coliforms and E. coli may not be
      suitable as indicators for enteric viruses in a meat processing environment.

PMID- 22856577
TI  - Depuration of Oysters (Crassostrea gigas) contaminated with Vibrio
      parahaemolyticus and Vibrio vulnificus with UV light and chlorinated seawater.
AB  - The efficacy of depuration using UV light and chlorinated seawater for
      decontaminating Vibrio parahaemolyticus and Vibrio vulnificus from oysters was
      investigated. Oysters were contaminated with a five-strain cocktail of V.
      parahaemolyticus or V. vulnificus  to levels of 10(4) to 10(5) CFU ml(-1) for
      bioaccumulation. The depuration was conducted in a closed system in which 350
      liters of seawater was recirculated at a rate of 7 liters/min for 48 h at room
      temperature. Counts of V. parahaemolyticus or V.  vulnificus were determined at
      0, 6, 18, 24, and 48 h. Three treatments were conducted: T1, control treatment;
      T2, UV treatment; and T3, UV plus chlorine treatment. After 48 h of depuration of
      V. parahaemolyticus, T3 reduced the count by 3.1 log most probable number (MPN)
      g(-1)  and T2 reduced the count by 2.4 log MPN g(-1), while T1 reduced the count
      by only 2.0 log MPN g(-1). After 48 h of depuration of V. vulnificus, T2 and T3
      were efficient, reducing the counts by 2.5 and 2.4 log MPN g(-1), respectively,
      while  T1 reduced the count by only 1.4 log MPN g(-1). The UV light plus chlorine
      treatment was more efficient for controlling V. parahaemolyticus in oysters. Both
      UV light and UV light plus chlorine were efficient for V. vulnificus. The present
      study is the first report  showing the efficacy of depuration systems for
      decontaminating V. parahaemolyticus and V. vulnificus in oysters cultivated on
      the Brazilian coast. This study provides information on processes that can
      contribute to controlling and preventing such microorganisms in oysters and 
      could be used for effective postharvest treatment by restaurants and small
      producers of oysters on the coast of Brazil.

PMID- 22856578
TI  - Modulation of cell surface hydrophobicity and attachment of bacteria to abiotic
      surfaces and shrimp by Malaysian herb extracts.
AB  - The use of simple crude water extracts of common herbs to reduce bacterial
      attachment may be a cost-effective way to control bacterial foodborne pathogens,
      particularly in developing countries. The ability of water extracts of three
      common Malaysian herbs (Andrographis paniculata,  Eurycoma longifolia, and
      Garcinia atroviridis) to modulate hydrophobicity and attachment to surfaces of
      five food-related bacterial strains (Bacillus cereus ATCC 14576, Escherichia coli
      ATCC 25922, Pseudomonas aeruginosa ATCC 10145, Salmonella Enteritidis  ATCC
      13076, Staphylococcus aureus ATCC 25923) were determined. The bacterial
      attachment to hydrocarbon assay was used to determine bacterial hydrophobicity.
      Staining and direct microscopic counts were used to determine attachment of
      bacteria to glass and stainless steel. Plating on  selective media was used to
      determine attachment of bacteria to shrimp. All extracts were capable of either
      significantly ( P < 0.05) increasing or decreasing bacterial surface
      hydrophobicity, depending on the herb extract and bacteria combination. Bacterial
      attachment to all surfaces  was either significantly (P < 0.05) increased or
      decreased, depending on the herb extract and bacteria combination. Overall,
      hydrophobicity did not show a significant correlation (P > 0.05) to bacterial
      attachment. For specific combinations of bacteria, surface material,  and plant
      extract, significant correlations (R > 0.80) between hydrophobicity and
      attachment were observed. The highest of these was observed for S. aureus
      attachment to stainless steel and glass after treatment with the E. longifolia
      extract (R = 0.99, P  < 0.01). The crude water herb extracts in this study were
      shown to have the potential to modulate specific bacterial and surface
      interactions and may, with further work, be useful for the simple and practical
      control of foodborne pathogens.

PMID- 22856579
TI  - Prevalence and antimicrobial resistance of Cronobacter sakazakii isolated from
      domestic kitchens in middle Tennessee, United States.
AB  - Cronobacter sakazakii is an emerging opportunistic pathogen that has been
      implicated in cases of severe meningitis, sepsis, and necrotizing enterocolitis
      in premature and full-term infants. In this study, the prevalence of C. sakazakii
      was estimated in selected domestic  kitchens in middle Tennessee. Antimicrobial
      resistance patterns of these C. sakazakii isolates were examined for points of
      public health significance. A total of 234 contact sites in 78 domestic kitchens
      were tested for C. sakazakii. Consumers' used dishcloths and cleaning sponges 
      were also tested. Antimicrobial susceptibility of the identified C. sakazakii
      isolates was determined for 10 antimicrobial drugs by means of the disk diffusion
      method. C. sakazakii was recovered from 26.9% of domestic kitchens visited.
      Multidrug resistance was observed; the highest  resistance was to penicillin
      (76.1% of isolates) followed by tetracycline (66.6%), ciprofloxacin (57.1%), and
      nalidixic acid (47.6%). None of the C. sakazakii isolates were resistant to
      gentamicin. These results suggest that antibiotic-resistant C. sakazakii could be
      present  at various sites in domestic kitchens.

PMID- 22856580
TI  - Performance of three culture media commonly used for detecting Listeria
      monocytogenes.
AB  - Listeria monocytogenes poses a serious threat to public health, and the majority
      of cases of human listeriosis are associated with contaminated food. Reliable
      microbiological testing is needed for effective control of this pathogen by the
      food industry and competent authorities.  The aim of this study was to determine
      the performance of three culture media commonly used for detecting L.
      monocytogenes in foods. Minced pork meat samples (n = 100) were subjected to
      microbiological testing for L. monocytogenes according to International
      Organization  for Standardization methods 11290-1:1996 and 11290-2:1998 using
      PALCAM, ALOA, and RAPID'L. mono culture media in parallel. Presence of the
      pathogen was confirmed by conducting biochemical and molecular tests on the
      presumptive L. monocytogenes colonies. Performance attributes of sensitivity, 
      specificity, positive and negative predictive values, positive and negative
      likelihood ratios, diagnostic odds ratios, error odds ratios, receiving operating
      characteristic (ROC) curve, and area under this curve were calculated from the
      presence-absence microbiological test results by combining  the results obtained
      from the culture media and confirmative tests. PALCAM had the best performance in
      terms of positive predictive value (i.e., a positive result indicates high
      probability of L. monocytogenes presence) but not in terms of sensitivity (i.e.,
      the ability of the medium  to detect the pathogen when present). RAPID'L. mono
      was the most sensitive medium. None of the culture media were perfect for
      detecting L. monocytogenes in minced pork meat alone. The pathogen was detected
      in 16, 19, and 26% (apparent prevalence) of the samples by PALCAM, ALOA, and 
      RAPID'L. mono, respectively, although the true prevalence of the pathogen was
      22%. These findings indicate that the use of a single culture medium may lead to
      erroneous determination of the prevalence of L. monocytogenes.

PMID- 22856581
TI  - Vacuum-packed beef primals with extremely long shelf life have unusual
      microbiological counts.
AB  - When vacuum-packed striploins and cube rolls processed by six Australian
      establishments were stored at 2 0.5 degrees C to determine their shelf life, all
      product was acceptable organoleptically for at least 26 weeks. The aerobic plate
      counts and counts of lactic acid bacteria over the storage  period did not accord
      with those established by previous studies, i.e., stationary phase attained at 7
      to 8 log CFU/cm(2) after 5 to 8 weeks followed by the development of negative
      sensory characteristics around 12 to 16 weeks. Rather, counts rarely progressed
      to 7 log CFU/cm(2)  even after 30 weeks. It is believed that the combined effects
      of meat pH, temperature, and CO(2) concentration may combine to create conditions
      in which little or no growth occurs.

PMID- 22856582
TI  - Mold and aflatoxin reduction by gamma radiation of packed hot peppers and their
      evolution during storage.
AB  - The effect of gamma radiation on moisture content, total mold counts, Aspergillus
      counts, and aflatoxins of three hot pepper hybrids (Sky Red, Maha, and Wonder
      King) was investigated. Whole dried peppers packed in polyethylene bags were
      gamma irradiated at 0 (control), 2, 4,  and 6 kGy and stored at 25 degrees C for
      90 days. Gamma radiation proved to be effective in reducing total mold and
      Aspergillus counts in a dose-dependent relationship. Total mold counts in
      irradiated peppers immediately after treatments were significantly lowered
      compared with those in  nonirradiated samples, achieving 90 and 99% reduction at
      2- and 4-kGy doses, respectively. Aspergillus counts were significantly reduced,
      by 93 and 97%, immediately after irradiation at doses of 2 and 4 kGy,
      respectively. A radiation dose of 6 kGy completely eliminated the population  of
      total molds and Aspergillus fungi. The evolution of total molds in control and
      irradiated samples indicated no further fungal proliferation during 3 months of
      storage at 25 degrees C. Aflatoxin levels were slightly affected by radiation
      doses of 2 and 4 kGy and showed a nonsignificant  reduction of 6% at the highest
      radiation dose of 6 kGy. The distinct effectiveness of gamma radiation in molds
      and aflatoxins can be explained by the target theory of food irradiation, which
      states that the likelihood of a microorganism or a molecule being inactivated by
      gamma rays increases  as its size increases.

PMID- 22856583
TI  - Efficacy of a levulinic acid plus sodium dodecyl sulfate-based sanitizer on
      inactivation of human norovirus surrogates.
AB  - Human noroviruses are the most common etiologic agent of foodborne illness in the
      United States. The inability to culture human noroviruses in the laboratory
      necessitates the use of surrogate viruses such as murine norovirus (MNV-1) and
      feline calicivirus (FCV) for inactivation studies.  In this study, a novel
      sanitizer of organic acid (levulinic acid) plus the anionic detergent sodium
      dodecyl sulfate (SDS) was evaluated. Viruses were treated with levulinic acid
      (0.5 to 5%), SDS (0.05 to 2%), or combinations of levulinic acid plus SDS (1:10
      solution of virus to sanitizer).  MNV-1 inoculated onto stainless steel also was
      treated with a 5% levulinic acid plus 2% SDS liquid or foaming solution. Log
      reductions of viruses were determined with a plaque assay. Neither levulinic acid
      nor SDS alone were capable of inactivating MNV-1 or FCV, resulting in a <=0.51
      log  reduction of the infectious virus titer. However, the combination of 0.5%
      levulinic acid plus 0.5% SDS inactivated both surrogates by 3 to 4.21 log PFU/ml
      after 1 min of exposure. Similarly, MNV-1 inoculated onto stainless steel was
      reduced by >1.50 log PFU/ml after 1 min and by >3.3  log PFU/ml after 5 min of
      exposure to a liquid or foaming solution of 5% levulinic acid plus 2% SDS. The
      presence of organic matter (up to 10%) in the virus inoculum did not
      significantly affect sanitizer efficacy. The fact that both of the active
      sanitizer ingredients are generally recognized  as safe to use as food additives
      by the U.S. Food and Drug Administration further extends its potential in
      mitigating foodborne disease.

PMID- 22856584
TI  - Histology as a valid and reliable tool to differentiate fresh from frozen-thawed
      fish.
AB  - Selling fish products as fresh when they have actually been frozen and thawed is
      a common fraudulent practice in seafood retailing. Unlike fish products frozen to
      protect them against degenerative changes during transportation and to extend the
      product's storage life, fish intended  for raw consumption in European countries
      must be previously frozen at -20 degrees  C for at least 24 h to kill parasites.
      The aim of this study was to use histological analysis to distinguish between
      fresh and frozen-thawed fish and to evaluate this method for use as a routine
      screening  technique in compliance with the requirements of European Commission
      Regulation No. 882/2004 on official food and feed controls. Method performance
      (i.e., accuracy and precision) was evaluated on tissue samples from three common
      Mediterranean fish species; the evaluation was subsequently extended  to include
      samples from 35 fish species in a second experiment to test for method
      robustness. Method accuracy was tested by comparing histological results against
      a "gold standard" obtained from the analysis of frozen and unfrozen fish samples
      prepared for the study. Method precision  was evaluated according to interrater
      agreement (i.e., three laboratories with expertise in histopathology in the first
      experiment and three expert analysts in the second experiment) by estimating
      Cohen's kappa (and corresponding 95 % confidence intervals) for each pair of
      laboratories and  experts and the combined Cohen's kappa for all three experts
      and laboratories. The observed interrater agreement among the three laboratories
      and the three experts indicated high levels of method accuracy and precision
      (high sensitivity and specificity) and method reproducibility. Our results 
      suggest that histology is a rapid, simple, and highly accurate method for
      distinguishing between fresh and frozen-thawed fish, regardless of the fish
      species analyzed.

PMID- 22856585
TI  - Examining the role of information exchange in residential aged care work
      practices--a survey of residential aged care facilities.
AB  - BACKGROUND: The provision of residential aged care is underpinned by information,
      and is reliant upon systems that adequately capture and effectively utilise and
      communicate this information. The aim of this study was to explicate and quantify
      the volume and method by which information is collected, exchanged within
      facilities and with external providers, and retrieved from facility information
      systems and hospitals. METHODS: A survey of staff (n = 119), including managers,
      health informatics officers (HIOs), quality improvement staff, registered nurses
      (RNs), enrolled nurses (ENs)/endorsed enrolled nurses (EENs) and assistants in
      nursing (AINs) was carried out in four residential aged care facilities in New
      South Wales and Victoria, Australia. Sites varied in size and displayed a range
      of information technology (IT) capabilities. The survey investigated how and by
      whom information is collected, retrieved and exchanged, and the frequency and
      amount of time devoted to these tasks. Descriptive analysis was performed using
      SPSS, and open responses to questions were coded into key themes. RESULTS: Staff
      completed a median of six forms each, taking a median of 30 min per shift. 68.8%
      of staff reported transferring information from paper to a computer system, which
      took a median of 30 min per shift. Handover and face-to-face communication was
      the most frequently used form of information exchange within facilities. There
      was a large amount of faxing and telephone communication between facility staff
      and General Practitioners and community pharmacists, with staff reporting sending
      a median of 2 faxes to pharmacy and 1.5 faxes to General Practitioners, and
      initiating 2 telephone calls to pharmacies and 1.5 calls to General Practitioners
      per shift. Only 38.5% of respondents reported that they always had information
      available at the point-of-care and only 35.4% of respondents reported that they
      always had access to hospital stay information of residents after hospital
      discharge. CONCLUSIONS: This survey identified a high volume of information
      exchange activities, as well as inefficient procedures, such as the transfer of
      information from paper to computer systems and the reliance upon faxes for
      communication with external providers. These findings contribute to evidence for
      the need for interoperable IT systems to allow more efficient and reliable
      information exchange between facilities and external providers.

PMID- 22856586
TI  - Total protein, animal protein and physical activity in relation to muscle mass in
      middle-aged and older Americans.
AB  - Resistance training is recognised as a good strategy for retarding age-related
      declines in muscle mass and strength. Recent studies have also highlighted the
      potential value of protein intakes in excess of present recommendations. The
      roles that leisure-time physical activity and protein quality play in the
      preservation of skeletal muscle during ageing, and how such influences interact
      in free-living people are unclear. We sought to clarify these issues using data
      collected on 2425 participants aged >= 50 years in the US National Health and
      Nutrition Examination Survey (2003-2006). We estimated subjects' usual intakes of
      total protein and beef from two 24 h diet recalls and computed the appendicular
      skeletal muscle mass index from anthropometric measures. Participants self
      reported their physical activity levels. Analyses accounted for demographic
      factors and smoking. The association between muscle-strengthening activity and
      the appendicular skeletal muscle mass index varied with protein intake.
      Furthermore, among obese subjects with protein intakes < 70 g/d, those who
      performed such activities had a lower appendicular skeletal muscle mass index
      than those who were physically inactive. Protein intakes above the present
      recommendations were associated with benefits to obese subjects only. The
      appendicular skeletal muscle mass index of non-obese subjects who performed
      vigorous aerobic activities was consistently high; in obese subjects, it varied
      with protein intake. High-protein intake was associated with a modest increase in
      the appendicular skeletal muscle mass index in non-obese, physically inactive
      subjects. The present findings reinforce the idea that muscle-strengthening
      exercise preserves muscle when combined with adequate dietary protein. Vigorous
      aerobic activity may also help.

PMID- 22856587
TI  - The law of Bergonie and Tribondeau: a nice formula for a first approximation.
AB  - PURPOSE: By extending to other animal models the experiments on irradiated rabbit
      testes performed by the German Albers-Schonberg and Frieben and inspired by the
      preliminary observations of Regaud on spermatogenesis after irradiation, Bergonie
      and Tribondeau established a link between radiosensitivity and proliferation as a
      'law' in 1906. Although it is still popular and taken as one of the founding laws
      of radiation oncology, it was early considered as a 'first approximation'.
      CONCLUSIONS: More than 100 years later, one tribute paid to these pioneers should
      be to at least avoid mixing notions like radiosensitivity, proliferation,
      differentiation, stem cells that they deeply contributed to define and to re-read
      their works in their original version in order to better understand what the
      technological and conceptual advances really are today.

PMID- 22856588
TI  - Patient perspectives on personalized glucose advisory systems for type 1 diabetes
      management.
AB  - BACKGROUND: Diabetes technology is rapidly advancing toward fully automated
      glucose control systems, but little is known about patient perspectives on these
      systems. This study aimed to gather qualitative and quantitative data on patient
      attitudes and concerns about using a personalized glucose advisory system
      (PGASystem) for diabetes management. SUBJECTS AND METHODS: Fifty-six adults with
      type 1 diabetes on insulin pump therapy participated in focus group interviews
      following use of an insulin pump and continuous glucose monitoring for 4 weeks in
      a parent study to develop a PGASystem. Focus groups were transcribed and coded
      for thematic content. RESULTS: All participants endorsed the desire to use a
      PGASystem, and the majority wanted advice from the system on all aspects of
      insulin delivery. However, participants indicated that they might be reluctant to
      follow such advice because of the following concerns: how the advice was
      generated, relinquishing control to automated technology, and inadequate
      personalization of the system. Participants believed the system would need to
      consider numerous factors related to their food, activities, and other personal
      information to provide optimally individualized advice. The majority also
      reported difficulties with behavioral event recording on their insulin pumps, and
      approximately one-third endorsed difficulty with accurate carbohydrate counting.
      CONCLUSIONS: Adults with type 1 diabetes appear to be enthusiastic about using a
      PGASystem system for their diabetes management but also have significant concerns
      affecting their overall willingness to follow such a system's advice. Addressing
      these concerns will be crucial in the future development of glucose advisory and
      control technology.

PMID- 22856589
TI  - Synthesis and structure determination of a new microporous zeolite with large
      cavities connected by small pores.
AB  - A new small-pore germanosilicate zeolite, named as ITQ-49, has been synthesized
      using a new ditetraalkylphosphonium dication as an organic structure-directing
      agent, and its structure has been solved by direct methods applied to the powder
      X-ray diffraction pattern of the calcined solid. This new zeolite crystallizes in
      the space group Immm with cell parameters a = 19.6007(8) A, b = 18.3274(7) A, and
      c = 16.5335(6) A. The pore topology of ITQ-49 consists of large, nonspherical
      cavities that are connected to each other through small eight-membered-ring
      windows, resulting in a unidirectional small-pore zeolite that has a relatively
      large adsorption capacity. Also, ITQ-49 contains double four-membered-ring units
      where Ge is preferentially located, and fluoride anions are placed inside these
      units.

PMID- 22856590
TI  - Genome-wide profiling in melatonin-exposed human breast cancer cell lines
      identifies differentially methylated genes involved in the anticancer effect of
      melatonin.
AB  - Epigenetic alterations have emerged as an important mechanism involved in
      tumorigenesis. The epigenetic impact of DNA methylation in various types of human
      cancer is not completely understood. Previously, we observed melatonin-induced
      differential expression of miRNA and miRNA-related genes in human breast cancer
      cell lines that indicated an anticancer effect of melatonin. In this report, we
      further characterized epigenetic changes in melatonin-exposed MCF-7 cells through
      the analysis of DNA methylation profiles in breast cancer cells to provide new
      insights into the potential mechanisms of the anticancer effect of melatonin.
      Microarray-based DNA methylation and gene expression profiling were carried out
      using human breast cancer cell lines. We further identified a number of mRNAs
      whose expression levels show an inverse correlation with DNA methylation levels.
      The mRNA expression levels and methylation status of candidate genes in melatonin
      exposed cells were confirmed by real-time quantitative PCR and bisulfite PCR.
      This approach led to the detection of cancer-related genes, which were oncogenic
      genes, including EGR3 and POU4F2/Brn-3b were down-regulated, while the tumor
      suppressor gene, GPC3, was up-regulated by 1 nm melatonin-treated MCF-7 cells.
      Our results provide detailed insights into the DNA methylation patterns induced
      by melatonin and suggest a potential mechanism of the anticancer effect of
      aberrant DNA methylation in melatonin-treated breast cancer cells.

PMID- 22856591
TI  - Enhanced epoxy/silica composites mechanical properties by introducing graphene
      oxide to the interface.
AB  - Controlling the interface interaction of polymer/filler is essential for the
      fabrication of high-performance polymer composites. In this work, a core-shell
      structured hybrid (SiO(2)-GO) was prepared and introduced into an epoxy polymer
      matrix as a new filler. The incorporation of the hybrid optimized the modulus,
      strength and fracture toughness of the composites simultaneously. The ultrathin
      GO shells coated on silica surfaces were regarded as the main reason for the
      enhancement. Located at the silica-epoxy interface, GO served as an
      unconventional coupling agent of the silica filler, which effectively enhanced
      the interfacial interaction of the epoxy/SiO(2)-GO composites, and thus greatly
      improved the mechanical properties of the epoxy resin. We believe this new and
      effective approach that using GO as a novel fillers surface modifier may open a
      novel interface design strategy for developing high performance composites.

PMID- 22856593
TI  - Role of zinc in severe pneumonia: a randomized double bind placebo controlled
      study.
AB  - BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children.
      OBJECTIVE: The aim of study was to evaluate the efficacy of Zinc supplementation
      in treatment of severe pneumonia in hospitalized children. DESIGN/METHODS: A
      double blind randomized, placebo- controlled clinical trial conducted at a
      tertiary care centre of a teaching hospital. Children with diagnosis of severe
      pneumonia were randomly assigned to receive supplementation with either elemental
      zinc or placebo by mouth at the time of enrollment. From day 2, they received 10
      mg of their assigned treatment by mouth twice a day for 7 days along with
      standard antimicrobial therapy. RESULTS: The baseline characteristics like age,
      sex, weight, weight Z score, height, height Z score, weight for height Z score
      and hemoglobin were comparable in both study groups. The respiratory rate, chest
      indrawing, cyanosis, stridor, nasal flaring, wheeze and fever in both groups
      recorded at enrollment and parameters did not differ significantly between the
      two groups. The outcome measures like time taken for resolution of severe
      pneumonia, pneumonia, duration of hospital stay, nil per oral, intravenous fluid,
      oxygen use, treatment requiring 2nd line of drug and 3rd line drug were evaluated
      and found to be same. CONCLUSION: The present study did not show a statistically
      significant reduction in duration of severe pneumonia, or reduction in hospital
      stay for children given daily zinc supplementation along with standard
      antimicrobial therapy. Therefore, zinc supplementation given during the acute
      episode does not help in short term clinical recovery from severe pneumonia.

PMID- 22856594
TI  - Inhalation therapy in patients receiving mechanical ventilation: an update.
AB  - Incremental gains in understanding the influence of various factors on aerosol
      delivery in concert with technological advancements over the past 2 decades have
      fueled an ever burgeoning literature on aerosol therapy during mechanical
      ventilation. In-line use of pressurized metered-dose inhalers (pMDIs) and
      nebulizers is influenced by a host of factors, some of which are unique to
      ventilator-supported patients. This article reviews the impact of various factors
      on aerosol delivery with pMDIs and nebulizers, and elucidates the correlation
      between in-vitro estimates and in-vivo measurement of aerosol deposition in the
      lung. Aerosolized bronchodilator therapy with pMDIs and nebulizers is commonly
      employed in intensive care units (ICUs), and bronchodilators are among the most
      frequently used therapies in mechanically ventilated patients. The use of inhaled
      bronchodilators is not restricted to mechanically ventilated patients with
      chronic obstructive pulmonary disease (COPD) and asthma, as they are routinely
      employed in other ventilator-dependent patients without confirmed airflow
      obstruction. The efficacy and safety of bronchodilator therapy has generated a
      great deal of interest in employing other inhaled therapies, such as surfactant,
      antibiotics, prostacyclins, diuretics, anticoagulants and mucoactive agents,
      among others, in attempts to improve outcomes in critically ill ICU patients
      receiving mechanical ventilation.

PMID- 22856595
TI  - A methodological overview on molecular preimplantation genetic diagnosis and
      screening: a genomic future?
AB  - The genetic diagnosis and screening of preimplantation embryos generated by
      assisted reproduction technology has been consolidated in the prenatal care
      framework. The rapid evolution of DNA technologies is tending to molecular
      approaches. Our intention is to present a detailed methodological view, showing
      different diagnostic strategies based on molecular techniques that are currently
      applied in preimplantation genetic diagnosis. The amount of DNA from one single,
      or a few cells, obtained by embryo biopsy is a limiting factor for the molecular
      analysis. In this sense, genetic laboratories have developed molecular protocols
      considering this restrictive condition. Nevertheless, the development of whole
      genome amplification methods has allowed preimplantation genetic diagnosis for
      two or more indications simultaneously, like the selection of histocompatible
      embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular
      techniques have permitted preimplantation genetic screening to progress, by
      implementing microarray-based comparative genome hybridization. Finally, a future
      view of the embryo-genetics field based on molecular advances is proposed. The
      normalization, cost-effectiveness analysis, and new technological tools are the
      next topics for preimplantation genetic diagnosis and screening. Concomitantly,
      these additions to assisted reproduction technologies could have a positive
      effect on the schedules of preimplantation studies.

PMID- 22856596
TI  - Dendrochemistry of multiple releases of chlorinated solvents at a former
      industrial site.
AB  - Trees can take up and assimilate contaminants from the soil, subsurface, and
      groundwater. Contaminants in the transpiration stream can become bound or
      incorporated into the annual rings formed in trees of the temperate zones. The
      chemical analysis of precisely dated tree rings, called dendrochemistry, can be
      used to interpret past plant interactions with contaminants. This investigation
      demonstrates that dendrochemistry can be used to generate historical scenarios of
      past contamination of groundwater by chlorinated solvents at a site in Verl,
      Germany. Increment cores from trees at the Verl site were collected and analyzed
      by energy-dispersive X-ray fluorescence (EDXRF) line scanning. The EDXRF profiles
      showed four to six time periods where tree rings had anomalously high
      concentrations of chlorine (Cl) as an indicator of potential contamination by
      chlorinated solvents.

PMID- 22856597
TI  - A high-affinity ErbB4Fc fusion protein is a potent antagonist of heregulin
      mediated receptor activation.
AB  - Ligand-mediated activation of ErbB3 and ErbB4 is implicated in the pathogenesis
      of several human malignancies including cancer of the ovary and melanoma. We have
      used the broad ErbB ligand specificity of ErbB4 to assemble and express an ErbB4
      fusion protein comprising the first 497 amino acids of the mature ErbB4
      ectodomain fused to the human IgG Fc constant region. The purified fusion
      protein, designated sErbB4.497.Fc, binds the ErbB receptor ligands betacellulin
      and heregulin-beta1 (HRG-beta1) with high affinity (K(D) = 130 pM), an increase
      in affinity of 10- to 20-fold, respectively, compared with sErbB4.615.Fc.
      sErbB4.497.Fc inhibited ligand-stimulated phosphorylation of epidermal growth
      factor receptor and ErbB2, and blocked HRG-beta1 activation of the
      IKB/MAP/JNK/AKT signalling pathways. sErbB4.497.Fc inhibited HRG-beta1-stimulated
      proliferation in MCF7 cells. In a mouse tumour xenograft model, sErbB4.497.Fc as
      a monotherapy modestly inhibited the growth of MDA-MB-231 breast cancer cells.
      sErbB4.497.Fc may be useful in an adjuvant setting in combination with
      conventional therapeutic agents.

PMID- 22856598
TI  - Clinical tolerability of artesunate-amodiaquine versus comparator treatments for
      uncomplicated falciparum malaria: an individual-patient analysis of eight
      randomized controlled trials in sub-Saharan Africa.
AB  - BACKGROUND: The widespread use of artesunate-amodiaquine (ASAQ) for treating
      uncomplicated malaria makes it important to gather and analyse information on its
      tolerability. METHODS: An individual-patient tolerability analysis was conducted
      using data from eight randomized controlled clinical trials conducted at 17 sites
      in nine sub-Saharan countries comparing ASAQ to other anti-malarial treatments.
      All patients who received at least one dose of the study drug were included in
      the analysis. Differences in adverse event (AE) and treatment emergent adverse
      event (TEAE) were analysed by Day 28. RESULTS: Of the 6,179 patients enrolled
      (74% <5 years of age), 50% (n = 3,113) received ASAQ, 20% (n = 1,217) another
      ACT, and 30% (n = 1,849) a non-ACT (combination or single-agent) treatment.
      Overall, 8,542 AEs were recorded. The proportion of patients experiencing at
      least one gastro-intestinal AE on ASAQ was 43% (and higher than that with
      artemether-lumefantrine and dihydroartemisinin-piperaquine at two sites), and was
      23% for any other AEs (not different from other treatments). Specifically, the
      risk of diarrhoea, vomiting, cough and weakness was lower with artemether
      lumefantrine; artemether-lumefantrine and dihydroartemisinin-piperaquine carried
      a higher risk of pruritus, chloroquine-SP had a higher risk of nausea.
      Parasitological recurrence increased the risk of occurrence of any AE. No other
      difference was detected. Comparing AE to TEAE in patients who had pre-treatment
      occurrence and grades of intensity recorded, AEs were significantly more related
      to the pre-treatment prevalence of the symptom (p = 0.001, Fisher test); AEs
      overestimated TEAEs by a factor ranging from none to five-fold. The overall
      incidence of serious AEs (SAEs) with ASAQ was nine per 1,000 (29/3,113) and
      mortality was one per 1,000 (three deaths, none drug-related); both were similar
      to other treatments. CONCLUSION: ASAQ was comparatively well-tolerated. Safety
      information is important, and must be collected and analysed in a standardized
      way. TEAEs are a more objective measure of treatment-induced toxicity.

PMID- 22856599
TI  - Identification of nonessential regions of the nsp2 protein of an attenuated
      vaccine strain (HuN4-F112) of highly pathogenic porcine reproductive and
      respiratory syndrome virus for replication in marc-145 cell.
AB  - BACKGROUND: The regions in the middle of nonstructural protein 2 (nsp2) of
      porcine reproductive and respiratory syndrome virus (PRRSV) have been shown to be
      nonessential for PRRSV replication, and these nonessential regions are different
      in various viral strains. FINDING: In this study, the nonessential regions of the
      nsp2 of an attenuated vaccine strain (HuN4-F112) of highly pathogenic porcine
      reproductive and respiratory syndrome virus were identified based on an
      infectious cDNA clone of HuN4-F112. The results demonstrated that the segments of
      nsp2 [amino acids (aa) 480 to 667] tolerated deletions. Characterization of the
      mutants demonstrated that those with small deletions did not affect the viral
      growth on Marc-145 cells, but deletion of these regions led to earlier PRRSV
      replication increased (before 36 h after infectious in vitro). CONCLUSION: The
      functional roles of nsp2 variable middle region for PRRSV HuN4-F112 replication
      have been identified. Our results also suggested that none-essential region might
      be an ideal insertion region to express foreign gene in PRRSV genome.

PMID- 22856600
TI  - Editorial: The therapeutic sound of silencing: managing the expectations on
      targeting RNAi.

PMID- 22856601
TI  - Exosomes and the emerging field of exosome-based gene therapy.
AB  - Exosomes are a subtype of membrane vesicle released from the endocytic
      compartment of live cells. They play an important role in endogenous cell-to-cell
      communication. Previously shown to be capable of traversing biological barriers
      and to naturally transport functional nucleic acids between cells, they
      potentially represent a novel and exciting drug delivery vehicle for the field of
      gene therapy. Existing delivery vehicles are limited by concerns regarding their
      safety, toxicity and efficacy. In contrast, exosomes, as a natural cell-derived
      nanocarrier, are immunologically inert if purified from a compatible cell source
      and possess an intrinsic ability to cross biological barriers. Already utilised
      in a number of clinical trials, exosomes appear to be well-tolerated, even
      following repeat administration. Recent studies have shown that exosomes may be
      used to encapsulate and protect exogenous oligonucleotides for delivery to target
      cells. They therefore may be valuable for the delivery of RNA interference and
      microRNA regulatory molecules in addition to other single-stranded
      oligonucleotides. Prior to clinical translation, this nanotechnology requires
      further development by refinement of isolation, purification, loading, delivery
      and targeting protocols. Thus, exosome-mediated nanodelivery is highly promising
      and may fill the void left by current delivery methods for systemic gene therapy.

PMID- 22856602
TI  - Non-viral delivery of RNA interference targeting cancer cells in cancer gene
      therapy.
AB  - RNA interference (RNAi) is a collection of small RNA-directed mechanisms that
      result in sequence-specific inhibition of gene expression. RNAi delivery has
      demonstrated promising efficacy in the treatment of genetic disorders in cancer.
      Although viral vectors are currently the most efficient systems for gene therapy,
      potent immunogenicity, mutagenesis, and the biohazards of viral vectors remain
      their major risks. Various non-viral delivery vectors have been developed to
      provide a safer approach for gene delivery, including polymers, peptides,
      liposomes, and nanoparticles. However, some concerns and challenges of these non
      viral gene delivery approaches remain to be overcome. In this review, we
      summarize the recent progress in the development of non-viral systems delivering
      RNAi and the currently available preclinical and clinical data, and discuss the
      challenges and future directions in cancer therapy.

PMID- 22856603
TI  - MicroRNAs and the Warburg Effect: new players in an old arena.
AB  - It is known that tumor cells adapt characteristic metabolic phenotypes during
      cancer initiation and progression. The hallmark of tumor metabolism is aerobic
      glycolysis, or Warburg Effect, which was first described more than 80 years ago.
      Unlike normal cells, most cancer cells produce energy by a high rate of glycolic
      catabolism to lactate in the cytosol, rather than by oxidation of pyruvate in
      mitochondria, even in the presence of oxygen. Progress over the past decade has
      revealed that alterations of oncogenes and tumor suppressors are responsible for
      such metabolic reprogramming in cancer cells, however, the underlying molecular
      basis remains largely unknown. Mounting evidence shows the interplay between
      microRNAs and oncogenes/tumor suppressors, via key metabolic enzyme effecters,
      which could facilitate the Warburg Effect in cancer cells. In this review, we
      will summarize our current understanding of the roles of microRNAs, in particular
      their interplay with oncogenes/tumor suppressors such as cMyc, HIF-1 and P53, in
      tumor metabolism.

PMID- 22856604
TI  - MicroRNAs in genetic disease: rethinking the dosage.
AB  - To date, the general assumption was that most mutations interested protein-coding
      genes only. Thus, only few illustrations have mentioned here that mutations may
      occur in non-protein coding genes such as microRNAs (miRNAs). We thus report
      progress in delineating their contribution as phenotypic modulators, genetic
      switches and fine-tuners of gene expression. We reasoned that browsing their
      contribution to genetic disease may provide a framework for understanding the
      proper requirements to devise miRNA-based therapy strategies, in particular the
      relief of an appropriate dosage. Gain and loss of function of miRNA enforce the
      need to respectively antagonize or supply the miRNAs. We further categorized
      human disease according to the different ways in which the miRNA was altered
      arising either de novo, or inherited whether as a mendelian or as an epistatic
      trait, uncovering its role in epigenetics. We discuss how improving our knowledge
      on the contribution of miRNAs to genetic disease may be beneficial to devise
      appropriate gene therapy strategies.

PMID- 22856605
TI  - Combating hepatitis C virus by targeting microRNA-122 using locked nucleic acids.
AB  - MicroRNAs have been predicted to regulate the stability and translation of many
      target mRNAs that are involved in modulating disease outcome. Thus, valuable
      strategies to enhance or to diminish the function of microRNAs are needed to
      manipulate microRNA-mediated target gene expression. Recently, it has become
      apparent that one class of antisense oligonucleotides, locked nucleic acids, can
      be used to sequester microRNAs in the liver of a variety of animals including
      humans, opening the possibility of applying locked nucleic acid-mediated gene
      therapy. This review summarizes the success of sequestration of liver-specific
      microRNA miR-122 by antisense locked nucleic acids and their use in combating
      hepatitis C virus in clinical trials.

PMID- 22856607
TI  - Translational siRNA therapeutics using liposomal carriers: prospects &
      challenges.
AB  - Gene silencing has emerged as a promising strategy for molecular therapy of
      various malignant, viral, hereditary and inflammatory disorders. However, its
      translation from lab to clinic is yet to gain momentum due to the numerous
      problems that plague its development. A multi-functional siRNA delivery system
      with desired properties such as enhanced immune compatibility, target
      specificity, high cell uptake and excellent silencing efficiency is required to
      understand the challenges involved in the selection and modification of small
      interfering RNA (siRNA), factors influencing the complexation process and the
      response of the biological system to the formulation. Liposomes have been used as
      delivery systems due to its versatility in handling different types of drugs,
      tunable size, charge and surface functionalities that improve its effectiveness
      in vivo. This review highlights the challenges involved in gene silencing and
      describes the progression of liposomal systems used in gene silencing. The
      rationale in introducing chemical modifications in siRNA, synthesizing designer
      cationic lipids and evolution of hybrid liposomal systems has been elaborated,
      emphasizing their merits and short-comings. Finally, a description of the current
      state of clinical trials involving liposomal formulations has been included to
      provide an unbiased perspective of the future of liposomal systems and gene
      silencing tools as therapeutic tools.

PMID- 22856608
TI  - Adeno-associated virus vectors: immunobiology and potential use for immune
      modulation.
AB  - Recombinant viral vectors based on the human parvovirus, adeno-associated virus
      (AAV) show considerable promise for human therapeutic application. An important
      feature that sets this gene transfer system apart from other contemporary virus
      based systems is relatively weak induction of innate and cognate immune
      responses, such that in defined contexts foreign antigens can be expressed long
      term in immune competent hosts. This in turn has led to increasing interest in
      the possibility of exploiting AAV for immune system modulation, including both
      the induction and avoidance of antigen- specific responses, depending on the
      therapeutic need. This interest is fuelled by the recognition that the full
      potential of cell and gene based therapies cannot be realised without parallel
      developments in therapeutic immune system modulation that allow specific rather
      than generalised immunosuppression. This review outlines current understanding of
      AAV immunobiology and explores its potential as a tool for therapeutic
      manipulation of immune system responses.

PMID- 22856606
TI  - RNAi-based gene therapy for dominant Limb Girdle Muscular Dystrophies.
AB  - Limb Girdle Muscular Dystrophy (LGMD) refers to a group of 25 genetic diseases
      linked by common clinical features, including wasting of muscles supporting the
      pelvic and shoulder girdles. Cardiac involvement may also occur. Like other
      muscular dystrophies, LGMDs are currently incurable, but prospective gene
      replacement therapies targeting recessive forms have shown promise in pre
      clinical and clinical studies. In contrast, little attention has been paid to
      developing gene therapy approaches for dominant forms of LGMD, which would likely
      benefit from disease gene silencing. Despite the lack of focus to date on
      developing gene therapies for dominant LGMDs, the field is not starting at square
      one, since translational studies on recessive LGMDs provided a framework that can
      be applied to treating dominant forms of the disease. In this manuscript, we
      discuss the prospects of treating dominantly inherited forms of LGMD with gene
      silencing approaches.

PMID- 22856609
TI  - Fast-scan deposition-stripping voltammetry at carbon-fiber microelectrodes: real
      time, subsecond, mercury free measurements of copper.
AB  - Elevated concentrations of hazardous metals in aquatic systems are known to
      threaten human health. Mobility, bioavailability, and toxicity of metals are
      controlled by chemical speciation, a dynamic process. Understanding metal
      behavior is limited by the lack of analytical methods that can provide rapid,
      sensitive, in situ measurements. While electrochemistry shows promise, it is
      limited by its temporal resolution and the necessity for Hg modified electrodes.
      In this letter, we apply fast-scan deposition-stripping voltammetry at carbon
      fiber microelectrodes for in situ measurements of Cu(II). We present a novel, Hg
      free technique that can measure Cu(II) with ppb sensitivity at 100 ms temporal
      resolution.

PMID- 22856610
TI  - Effect of substrate temperature on the epitaxial growth of oriented n-alkane thin
      films on graphite.
AB  - A complex orientational morphology is observed when n-alkane thin films are vapor
      deposited on highly oriented pyrolytic graphite surfaces. Substrate temperature
      can be used to tune the orientation and morphology of n-alkane thin films. The
      molecular orientation changes from lateral to normal to the surface when the
      substrate temperature is raised sufficiently. Under specific substrate
      temperature conditions, the n-alkane molecules are aligned in the plane of the
      sample surface, in directions reflecting the 6-fold symmetry of the graphite
      substrate. A series of different morphologies, from uniform thin films to
      oriented bars, are observed as a function of chain length and substrate
      temperature. The systematic evolution of these oriented morphologies is mapped as
      a function of deposition conditions, and the kinetic and thermodynamic factors
      that govern the formation of different in-plane and normal domains are
      considered.

PMID- 22856611
TI  - The gender gap in mobility: a global cross-sectional study.
AB  - BACKGROUND: Several studies have demonstrated that women have greater mobility
      disability than men. The goals of this research were: 1) to assess the gender gap
      in mobility difficulty in 70 countries; 2) to determine whether the gender gap is
      explained by sociodemographic and health factors; 3) to determine whether the
      gender gap differs across 6 regions of the world with different degrees of gender
      equality according to United Nations data. METHODS: Population-based data were
      used from the World Health Survey (WHS) conducted in 70 countries throughout the
      world. 276,647 adults aged 18 years and over were recruited from 6 world regions.
      Mobility was measured by asking the level of difficulty people had moving around
      in the last 30 days and then creating a dichotomous measure (no difficulty,
      difficulty). The human development index and the gender-related development index
      for each country were obtained from the United Nations Development Program
      website. Poisson regression with Taylor series linearized variance estimation was
      used. RESULTS: Women were more likely than men to report mobility difficulty (38%
      versus 27%, P < 0.0001). The age-adjusted prevalence rate ratio for female gender
      was 1.35 (95% CI 1.31-1.38). The addition of education, marital status, and urban
      versus rural setting reduced the prevalence rate ratio to 1.30 (95% CI 1.26
      1.33). The addition of the presence of back pain, arthritis, angina, depressive
      symptoms, and cognitive difficulties further reduced the prevalence rate ratio to
      1.12 (95% CI 1.09-1.15). There was statistical interaction on the multiplicative
      scale between female gender and region (P < 0.01). The Eastern Mediterranean
      region, which had the greatest loss of human development due to gender
      inequality, showed the largest gender gap in mobility difficulty, while the
      Western Pacific region, with the smallest loss of human development due to gender
      inequality, had the smallest gender gap in mobility difficulty. CONCLUSIONS:
      These are the first world-wide data to examine the gender gap in mobility.
      Differences in chronic diseases are the main reasons for this gender gap. The
      gender gap seems to be greater in regions with the largest loss of human
      development due to gender inequality.

PMID- 22856612
TI  - Symptom validity indicators embedded in the Controlled Oral Word Association
      Test.
AB  - Embedded symptom validity measures facilitate the detection of below-capacity
      performance in neuropsychological assessment. A number of such indicators have
      been proposed for the Controlled Oral Word Association Test (COWAT), a widely
      used test of word generation. However, several of these embedded indicators have
      not been cross-validated and it is currently unclear which represent the optimal
      combination of predictors. This study used Bayesian Model Averaging (BMA) to
      determine the set of predictors that best differentiate between patients
      presenting with (n = 46) and without (n = 55) malingered neurocognitive
      dysfunction (MND). Mild traumatic brain injury was the most common diagnosis in
      the MND group (96%). BMA selected the COWAT total score and a measure of change
      in output over time. A logistic regression model combining these variables
      yielded good discriminability, with an AUC of. 774, (95% confidence interval =
      .679 to. 869), 78% of cases were classified correctly, with 67% sensitivity and
      88% specificity. Two alternative models performed similarly, but the variables
      involved required slightly longer administration and/or calculation time, making
      them somewhat less desirable. These results support the use of a weighted
      combination of embedded symptom validity measures in the COWAT.

PMID- 22856613
TI  - Vibration response imaging: a novel noninvasive tool for evaluating the initial
      therapeutic effect of noninvasive positive pressure ventilation in patients with
      acute exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: The popular methods for evaluating the initial therapeutic effect
      (ITE) of noninvasive positive pressure ventilation (NPPV) can only roughly
      reflect the therapeutic outcome of a patient's ventilation because they are
      subjective, invasive and time-delayed. In contrast, vibration response imaging
      (VRI) can monitor the function of a patient's ventilation over the NPPV therapy
      in a non-invasive manner. This study aimed to investigate the value of VRI in
      evaluating the ITE of NPPV for patients with acute exacerbation of chronic
      obstructive pulmonary disease (AECOPD). METHODS: Thirty-six AECOPD patients
      received VRI at three time points: before NPPV treatment (T1), at 15 min of NPPV
      treatment (T2), and at 15 min after the end of NPPV treatment (T4). Blood gas
      analysis was also performed at T1 and at 2 hours of NPPV treatment (T3). Thirty
      nine healthy volunteers also received VRI at T1 and T2. VRI examination at the
      time point T2 in either the patients or volunteers did not require any
      interruption of the on-going NPPV. The clinical indices at each time point were
      compared between the two groups. Moreover, correlations between the PaCO2 changes
      (T3 vs T1) and abnormal VRI scores (AVRIS) changes (T2 vs T1) were analyzed.
      RESULTS: No significant AVRIS differences were found between T1 and T2 in the
      healthy controls (8.51 +/- 3.36 vs. 8.53 +/- 3.57, P > 0.05). The AVRIS, dynamic
      score, MEF score and EVP score showed a significant decrease in AECOPD patients
      at T2 compared with T1 (P < 0.05), but a significant increase at T4 compared with
      T2 (P < 0.05). We also found a positive correlation (R2 = 0.6399) between the
      PaCO2 changes (T3 vs T1) and AVRIS changes (T2 vs T1). CONCLUSIONS: VRI is a
      promising noninvasive tool for evaluating the initial therapeutic effects of NPPV
      in AECOPD patients and predicting the success of NPPV in the early stage.

PMID- 22856614
TI  - ABO blood group, hypercoagulability, and cardiovascular and cancer risk.
AB  - The antigens of the ABO system (A, B, and H determinants, respectively) consist
      of complex carbohydrate molecules. It has been known for nearly half a century
      that the ABO blood group exerts a major influence on plasma levels of the von
      Willebrand factor (VWF)-factor VIII (FVIII) complex and that normal group O
      individuals have significantly lower levels of VWF and FVIII than do non-O
      individuals. As a consequence, several investigators have studied the association
      between ABO blood group and the risk of developing bleeding or thrombotic events.
      A number of epidemiological studies have also analyzed the biologic relevance of
      this interaction by assessing whether the ABO blood group could influence human
      longevity through the regulation of VWF-FVIII plasma levels. In this review, the
      molecular mechanisms by which the ABO blood group determines plasma VWF and
      consequently, FVIII levels, the possible clinical implications, and the current
      knowledge on the association between the ABO blood group and the risk of
      developing certain cancers will be reviewed.

PMID- 22856615
TI  - Social inhibition as a mediator of neuroticism and depression in the elderly.
AB  - BACKGROUND: A number of factors, such as demographics, cognitive function,
      personality and interpersonal relationship) play a role in late-life depression.
      This study investigates the influence of social inhibition on the inverse
      emotional stability (neuroticism) and depressive symptoms found in elderly Thai
      people. METHODS: In total, 123 elderly Thais aged 60 years of age or older were
      tested using the 64-item Inventory of Interpersonal Problems, Symptom Checklist
      90, and the 16 Personality Factors Questionnaire. Hierarchical regression and
      path analyses were performed in order to identify the relationships among these
      variables. RESULTS: The age of the participants ranged from 60 to 93 years old
      (mean = 71.7; SD = 6.2), and out of the group, 51.2% were male, 56.1% were
      married and 61.8% were on a low income. The average number of years spent in
      education among the participants was 7.6 (SD = 5.1). The variables found to be
      significantly associated with depression were age, intellect, social inhibition
      and possession of inverse emotional stability (neuroticism). Low levels of
      emotional stability were most strongly associated with depressive symptoms
      (standardized regression coefficients -0.29), but this effect was found to be
      reduced (mediated, to -0.26) by social inhibition. In total, 30% of the total
      variance could be explained by this model, and there was an excellent statistical
      fit. CONCLUSIONS: The variables found to be significantly associated with
      depression were a younger age, as well as lower levels of intellectual skill,
      social inhibition and inversed emotional stability (neuroticism). It was found
      that a lack of emotional stability is, along with a younger age, the strongest
      predictor of depressive symptoms, but can be mediated by social inhibition.

PMID- 22856616
TI  - Changes in waist circumference and body mass index in the US CARDIA cohort: fixed
      effects associations with self-reported experiences of racial/ethnic
      discrimination.
AB  - Prior studies examining the association between self-reported experiences of
      racial/ethnic discrimination and obesity have had mixed results and primarily
      been cross-sectional. This study tests the hypothesis that an increase in self
      reported experiences of racial/ethnic discrimination predicts gains in waist
      circumference and body mass index in Black and White women and men over eight
      years. In race/ethnicity- and gender-stratified models, this study examined
      whether change in self-reported experiences of racial/ethnic discrimination
      predicts changes in waist circumference and body mass index over time using a
      fixed-effects regression approach in SAS statistical software, providing control
      for both measured and unmeasured time-invariant covariates. Between 1992-93 and
      2000-01, self-reported experiences of racial/ethnic discrimination decreased
      among 843 Black women (75% to 73%), 601 Black men (80% to 77%), 893 White women
      (30% to 23%) and 856 White men (28% to 23%). In fixed-effects regression models,
      controlling for all time-invariant covariates, social desirability bias, and
      changes in education and parity (women only) over time, an increase in self
      reported experiences of racial/ethnic discrimination over time was significantly
      associated with an increase in waist circumference (beta=1.09, 95% CI: 0.00-2.19,
      p=0.05) and an increase in body mass index (beta=0.67, 95% CI: 0.19-1.16,
      p=0.007) among Black women. No associations were observed among Black men and
      White women and men. These findings suggest that an increase in self-reported
      experiences of racial/ethnic discrimination may be associated with increases in
      waist circumference and body mass index among Black women over time.

PMID- 22856617
TI  - Predictors of treatment use among foster mothers in an attachment-based
      intervention program.
AB  - The current study examined predictors of treatment use among 56 foster mothers
      who participated in an attachment-based intervention program for foster infants.
      Foster mothers' levels of treatment use were coded at early, middle, and late
      phases of the intervention program. Foster mothers' states of mind with regard to
      attachment predicted their understanding of the intervention session concepts.
      Specifically, autonomous foster mothers showed higher levels of understanding at
      the start of the intervention program, when compared with non-autonomous foster
      mothers. State of mind with regard to attachment also predicted foster mothers'
      levels of reflective functioning during the intervention sessions. Autonomous
      foster mothers showed higher levels of reflective functioning at early, middle,
      and late stages of the intervention program, when compared with non-autonomous
      foster mothers. The relevance of these findings for both treatment effectiveness
      and treatment delivery is discussed.

PMID- 22856618
TI  - Adult attachment representations predict cortisol and oxytocin responses to
      stress.
AB  - There are many factors contributing to individual variations in the response to
      stressful experiences. The present study evaluated the patterns of stress
      responses according to attachment representations in 28 adults from a community
      sample, plus 46 subjects expected to be particularly sensitive to stress, having
      been exposed during childhood and/or adolescence to traumatizing events such as
      abuse or potentially lethal illnesses. Subjects were given the Adult Attachment
      Interview, which provides attachment classifications, and the Trier Social Stress
      Test (TSST), involving an experimental psychosocial challenge. Subjective
      responses to the TSST, as well as saliva samples (assayed for cortisol) and blood
      plasma samples (assayed for ACTH and oxytocin) were collected before, during and
      after the stress procedure. The stress responses presented specific patterns
      according to attachment classifications. Subjects with an autonomous attachment
      classification reported relatively low subjective stress, they presented a
      moderate response of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and
      cortisol), and a high level of oxytocin. Subjects with a dismissing
      classification reported a moderate subjective stress, they presented an elevated
      response of the HPA axis, and moderate levels of oxytocin. Subjects with a
      preoccupied classification presented moderate levels of subjective stress, and of
      HPA response, and a relatively low level of oxytocin. Finally, subjects with an
      unresolved classification reported elevated subjective stress; they presented a
      suppressed HPA response, and moderate levels of oxytocin. These data support the
      notion that attachment representations may affect stress responses, and suggest a
      specific role of oxytocin in both the attachment system and the stress system.

PMID- 22856619
TI  - Regulating emotion expression and regulating emotion experience: divergent
      associations with dimensions of attachment among older women.
AB  - Adult attachment research does not systematically distinguish between
      experiential and expressive forms of regulation. Drawing insights from
      developmental-functionalism - a lifespan theory of emotion and emotion regulation
      - the current report examined the relations among attachment, trait emotion, and
      expressive emotion regulation in a large (N = 1204) sample of older women.
      Although both preoccupation and fearful-avoidance predicted more anxiety and
      anger, preoccupation predicted greater fear withdrawal and less fear expression,
      while fearful-avoidance predicted greater fear expression and greater anger
      withdrawal; attachment security predicted less fear withdrawal and less anger
      expression. Importantly, results regarding expressive regulation held even when
      controlling for trait levels of the underlying emotion. Results are interpreted
      within the context of models of attachment and lifespan socioemotional
      functioning. It is suggested that attachment research may benefit from
      considering the distinct functions of experienced versus expressed emotion in
      developmentally diverse contexts. Limitations are discussed and directions for
      future research are given.

PMID- 22856620
TI  - Script-like attachment representations in dreams containing current romantic
      partners.
AB  - Recent research has demonstrated parallels between romantic attachment styles and
      general dream content. The current study examined partner-specific attachment
      representations alongside dreams that contained significant others. The general
      prediction was that dreams would follow the "secure base script," and a general
      correspondence would emerge between secure attachment cognitions in waking life
      and in dreams. Sixty-one undergraduate student participants in committed dating
      relationships of six months duration or longer completed the Secure Base Script
      Narrative Assessment at Time 1, and then completed a dream diary for 14
      consecutive days. Blind coders scored dreams that contained significant others
      using the same criteria for secure base content in laboratory narratives. Results
      revealed a significant association between relationship-specific attachment
      security and the degree to which dreams about romantic partners followed the
      secure base script. The findings illuminate our understanding of mental
      representations with regards to specific attachment figures. Implications for
      attachment theory and clinical applications are discussed.

PMID- 22856621
TI  - Parent-child attachment and executive functioning in relation to ADHD symptoms in
      middle childhood.
AB  - This study investigated attachment representations and executive functioning
      (i.e., response inhibition and working memory) at age 81/2 in relation to ADHD
      symptoms one year later. Well-validated laboratory measures of both executive
      functioning and attachment representations were used. Additive, interaction, as
      well as mediation effects were investigated. The results showed that attachment
      disorganization and executive functioning were independently related to ADHD
      symptoms, even when using conduct problems as a covariate. No significant
      interaction effects were found, and executive functioning was not found to act as
      a mediator between attachment disorganization and ADHD symptoms. In conclusion,
      attachment disorganization had a significant effect on ADHD symptoms, independent
      of both executive functioning and conduct problems, which suggests that the
      parent-child attachment is a factor that needs to be included if we are to more
      fully understand the development of ADHD.

PMID- 22856623
TI  - The current role of statin therapy in the treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and one of the major
      causes of morbidity and hospitalization. It is an important risk factor for
      thromboembolic complications and cerebrovascular disease. In AF, extensive
      electrical and structural remodeling of atrial tissue takes place with the main
      underlying mechanisms being inflammation and fibrosis. In recent years it has
      been shown, that beside conventional antiarrhythmic therapies, modalities aiming
      at reversal of atrial tissue derangement could be of some benefit in the
      treatment of AF. In this respect, the main focus was oriented towards drugs such
      as angiotensin convertase (ACE) inhibitors, angiotensin receptor blockers (ARBs),
      polyunsaturated fatty acids and statins. Data about the potential beneficial role
      of statins for AF treatment is continuously growing. It is now evident that
      statins act on AF mainly through their pleiotropic and not their lipid lowering
      properties. Several retrospective trials have shown that statins exert
      antiarrhythmic effects in patients with AF, while data from prospective studies
      are still conflicting. Thus, the definitive confirmation and explanation of
      statin's role in AF treatment is still missing. Herein, the current
      patophysiological concepts providing rationale for the use of statins in AF
      treatment as well as up-to-date data from retrospective and prospective clinical
      studies are reviewed and discussed. Particular attention is paid to various
      clinical settings such as primary prevention, secondary prevention (post
      cardioversion) and postoperative setting. We also present our own data regarding
      the role of statins in prevention of the recurrence of AF after successful
      cardioversion.

PMID- 22856624
TI  - Does duration of untreated psychosis predict very long term outcome of
      schizophrenic disorders? results of a retrospective study.
AB  - BACKGROUND: Studies performed to assess the relevance of duration of untreated
      psychosis (DUP) as a predictor of long-term outcome (i.e. follow-ups of ten years
      or more) are somewhat limited. The aim of this study was to evaluate the
      potential association between DUP and very long-term outcome (16-33 yrs) of
      schizophrenia by means of a retrospective design. METHODS: Retrospective data
      obtained from clinical records were collected regarding DUP and outcome variables
      (number of hospitalizations; number of attempted suicides; course of illness; GAF
      scores at last observation) for a cohort of 80 outpatients (52 Males, 28 Females,
      mean age 51.0+/-11.58 years) affected by schizophrenia according to DSMIVTR
      attending a university community mental health centre. RESULTS: Mean duration of
      follow up was 25.2 +/- 8.68 years; mean duration of untreated psychosis was 49.00
      months (range 1-312 mo), with no significant difference according to gender.
      Patients with a shorter DUP (=/< 1 year) displayed more frequent "favourable"
      courses of illness (28.9% vs 8.6%) (p = 0.025), more frequent cases with limited
      (=/< 3) number of hospital admissions (85.7% vs 62.1%) (p = 0.047) and a better
      functioning (mean GAF score = 50.32+/-16.49 vs 40.26+/-9.60, p = 0.002);
      regression analyses confirmed that shorter DUP independently predicted a more
      positive outcome in terms of number of hospital admissions, course of illness,
      functioning (GAF scores). CONCLUSION: A shorter DUP appears to act as a
      significant predictor of better outcome in schizophrenia even in the very long
      term.

PMID- 22856625
TI  - Multilocus sequence analysis (MLSA) of 'Rickettsiella costelytrae' and
      'Rickettsiella pyronotae', intracellular bacterial entomopathogens from New
      Zealand.
AB  - AIMS: Larvae of scarab beetles live in the soil and are frequently hosts for
      microbial pathogens. In New Zealand, larvae of the grass grub, Costelytrae
      zealandica (Coleoptera: Scarabaeidae), and manuka beetles, Pyronota spp.
      (Coleoptera: Scarabaeidae), have been collected from field populations showing
      loss of vigour and a whitened appearance. Diagnosis indicated an intracellular
      infection of fat body tissues by Rickettsiella-like micro-organisms.
      Rickettsiella bacteria are under evaluation as a possible new source of insect
      bio-control agents for important agricultural pests as, e.g. scarabaeid and
      elaterid larvae. The present study aimed at the unequivocal molecular taxonomic
      identification and comparison of the bacteria associated with Costelytra and
      Pyronota. METHODS AND RESULTS: Electron microscopy and phylogenetic
      reconstruction using a multilocus sequence analysis approach based on the 16S
      ribosomal RNA gene together with four protein-encoding markers (ftsY, gidA, rpsA,
      and sucB) demonstrated that both bacteria from New Zealand are phylogenetically
      closely related, but not identical, and belong to the taxonomic genus
      Rickettsiella. CONCLUSIONS: The bacteria under study should be referred to as
      pathotypes 'Rickettsiella costelytrae' and 'Rickettsiella pyronotae',
      respectively. Moreover, on the basis of the currently accepted systematic
      organization of the genus Rickettsiella, both pathotypes should be considered
      synonyms of the nomenclatural type species, Rickettsiella popilliae. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The study demonstrates that Rickettsiella bacteria are
      geographically widespread pathogens of scarabaeid larvae. Implications of the
      phylogenetic findings presented for the stability of host adaptation by
      Rickettsiella bacteria are critically discussed.

PMID- 22856622
TI  - Impact of retrospective calibration algorithms on hypoglycemia detection in
      newborn infants using continuous glucose monitoring.
AB  - BACKGROUND: Neonatal hypoglycemia is common and may cause serious brain injury.
      Diagnosis is by blood glucose (BG) measurements, often taken several hours apart.
      Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while
      reducing the number of BG measurements. Calibration algorithms convert sensor
      signals into CGM output. Thus, these algorithms directly affect measures used to
      quantify hypoglycemia. This study was designed to quantify the effects of
      recalibration and filtering of CGM data on measures of hypoglycemia (BG <2.6
      mmol/L) in neonates. SUBJECTS AND METHODS: CGM data from 50 infants were
      recalibrated using an algorithm that explicitly recognized the high-accuracy BG
      measurements available in this study. CGM data were analyzed as (1) original CGM
      output, (2) recalibrated CGM output, (3) recalibrated CGM output with
      postcalibration median filtering, and (4) recalibrated CGM output with
      precalibration median filtering. Hypoglycemia was classified by number of
      episodes, duration, severity, and hypoglycemic index. RESULTS: Recalibration
      increased the number of hypoglycemic events (from 161 to 193), hypoglycemia
      duration (from 2.2% to 2.6%), and hypoglycemic index (from 4.9 to 7.1 MUmol/L).
      Median filtering postrecalibration reduced hypoglycemic events from 193 to 131,
      with little change in duration (from 2.6% to 2.5%) and hypoglycemic index (from
      7.1 to 6.9 MUmol/L). Median filtering prerecalibration resulted in 146
      hypoglycemic events, a total duration of hypoglycemia of 2.6%, and a hypoglycemic
      index of 6.8 MUmol/L. CONCLUSIONS: Hypoglycemia metrics, especially counting
      events, are heavily dependent on CGM calibration BG error, and the calibration
      algorithm. CGM devices tended to read high at lower levels, so when high accuracy
      calibration measurements are available it may be more appropriate to recalibrate
      the data.

PMID- 22856626
TI  - Diversity of HIV type 1 and drug resistance mutations among injecting drug users
      in Kenya.
AB  - Drug use in Kenya dates back to the precolonial period but research among drug
      users in relation to human immunodeficiency virus (HIV)-associated risk and
      intervention strategies has been low. To evaluate HIV-1 diversity and drug
      resistance among injecting drug users (IDUs), a cross-sectional study involving
      58 patients was carried out in Mombasa between February and March 2010. HIV-1 RNA
      was extracted from plasma and polymerase chain reaction using specific primers
      for HIV-1 reverse transcriptase was done. Population sequencing was done and
      subtypes were determined phylogenetically. The prevalent HIV-1 subtypes were A1
      (52/58), D (5/58), and C (2/58). The prevalence of drug resistance was 13.8%
      (8/58) with detection of nucleoside reverse transcriptase inhibitor (NRTI)
      mutations, T215F (n=5), K219Q (n=3), M184V (n=1), and nonnucleoside RTI mutation,
      K103N (n=1). Antiretroviral therapy (ART) and its monitoring among infected
      Kenyan IDUs is feasible. Policymakers and service providers in HIV prevention
      initiatives should improve service delivery so as to measure ART coverage among
      IDUs to prevent further transmission of drug-resistant variants.

PMID- 22856627
TI  - Melatonin prevents ultraviolet radiation-induced alterations in plasma membrane
      potential and intracellular pH in human keratinocytes.
AB  - Melatonin exhibits protective effects against ultraviolet radiation (UVR) via
      modulation of proinflammatory mediators and its free radical scavenging capacity.
      To date, several reports presented protective mechanisms of this agent against
      UVR-induced alterations in mitochondria and nuclei. This investigation evaluates
      the potent preventing action of melatonin regarding early-stage UVR-mediated
      perturbations in plasma membrane potential (mbDeltapsi) and intracellular
      (cytosolic) pH (pH i) analyzed by flow cytometry. Experiments were carried out in
      a dose- and time-dependent manner using human keratinocytes [HaCaT and normal
      human epidermal keratinocytes (NHEK)]. First investigations, which used
      viability/cytotoxicity assays, showed the gradual mortality with increasing UVR
      doses and cultivation time. Pre-incubation with melatonin (10(-3) m) prior to UVR
      exposure reduced lactate dehydrogenase release by 30% (HaCaT) and 28% (NHEK) at
      the dose of 50 mJ/cm(2) after 48 hr (P < 0.001). Furthermore, UVR caused
      hyperpolarization of mbDeltapsi immediately (0 hr) after irradiation (25 or 50
      mJ/cm(2)). At the dose of 50 mJ/cm(2), cells cultivated for 48 hr manifested a
      marked increase in mbDeltapsi by 112% (HaCaT) and 123% (NHEK). The presence of
      melatonin significantly protected the cells by 12% (HaCaT) and 14% (NHEK) (P <
      0.001). Simultaneously, 50 mJ/cm(2) induced dramatic acidification reaching after
      24 hr the level of 6.40 (without melatonin), 6.56 (with melatonin) for HaCaT and
      6.11 (without melatonin), 6.43 (with melatonin) for NHEK. The results presented
      provide information about the protective mechanisms of melatonin itself on one
      hand and, combined with data reported so far, confirm the potent antiapoptotic
      action of melatonin.

PMID- 22856628
TI  - Rapid methods to estimate potential exposure to semivolatile organic compounds in
      the indoor environment.
AB  - A systematic and efficient strategy is needed to assess and manage potential
      risks to human health that arise from the manufacture and use of thousands of
      chemicals. Among available tools for rapid assessment of large numbers of
      chemicals, significant gaps are associated with the capability to evaluate
      exposures that occur indoors. For semivolatile organic compounds (SVOCs),
      exposure is strongly influenced by the types of products in which these SVOCs
      occur. We propose methods for obtaining screening-level estimates for two primary
      SVOC source classes: additives in products used indoors and ingredients in
      products sprayed or applied to interior surfaces. Accounting for product use,
      emission characteristics, and the properties of the SVOCs, we estimate exposure
      via inhalation of SVOCs in the gas-phase, inhalation of SVOCs sorbed to airborne
      particles, ingestion of SVOCs sorbed to dust, and dermal sorption of SVOCs from
      the air into the blood. We also evaluate how exposure to the general public will
      change if chemical substitutions are made. Further development of a comprehensive
      set of models including the other SVOC-containing products and the other SVOC
      exposure pathways, together with appropriate methods for estimating or measuring
      the key parameters (in particular, the gas-phase concentration in equilibrium
      with the material-phase concentration of the SVOC in the product, or y(0)), is
      needed. When combined with rapid toxicity estimates, screening-level exposure
      estimates can contribute to health-risk-based prioritization of a wide range of
      chemicals of concern.

PMID- 22856629
TI  - Urinary fluticasone propionate-17beta-carboxylic acid to assess asthma therapy
      adherence.
AB  - Although the National Asthma Education and Prevention Program Expert Panel Report
      3 recommends referral to specialists to address adherence, guidelines do not
      provide a tool to determine nonadherence. This study was designed to
      prospectively evaluate the characteristics of urinary analysis of fluticasone
      propionate-17beta-carboxylic acid (FP17betaCA) as a test to verify if a specific
      patient has not taken fluticasone propionate (FP) within 16-24 hours. Urine of
      asthmatic subjects was prospectively analyzed 16-24 hours after witnessed
      administration of orally inhaled FP using liquid chromatography tandem mass
      spectrometry (LC-MS/MS) analysis; limit of quantitation was 10.3 pg/mL. Results
      were compared with those from asthmatic subjects not receiving inhaled FP. Thirty
      asthmatic subjects receiving inhaled FP (2 oral inhalations of FP at 110
      micrograms each or 1 oral inhalation twice daily of fluticasone and salmeterol in
      fixed combination at 250/50 micrograms for 1 week) were compared with 30
      asthmatic subjects not receiving FP. FP17betaCA was detected in the urine of 30
      of 30 asthmatic subjects receiving FP (median, interquartile range [IQR; 413.5,
      212.8-1230.0] range 12.4-3290.0 pg/mL [corrected for urine creatinine: median,
      IQR {576.2, 188.1-1306.6} range 6.3-5425.9 ng/g Cr]) and was undetectable in 30
      of 30 subjects not receiving inhaled FP. The sensitivity and specificity of LC
      MS/MS to detect FP17betaCA in urine were 100% (95% exact binomial confidence
      interval, 88-100) and 100% (95% exact binomial confidence interval, 88-100),
      respectively. Analysis of FP17betaCA in urine provides a sensitive method that
      may be used to verify that a specific patient may not have administered FP within
      a 16- to 24-hour window before testing.

PMID- 22856630
TI  - Hereditary angioedema: short-term prophylaxis for surgery.

PMID- 22856631
TI  - Difficult asthma: assessment and management, Part 1.
AB  - A minority of asthma patients have disease that proves difficult to control with
      usual medications and experience ongoing symptoms, poor quality of life, and
      limitations in activity and/or frequent asthma exacerbations. This group of
      patients accounts for much of the expense associated with asthma care and is the
      focus of national and international collaborative study groups. Distinguishing
      between "difficult-to-manage asthma" and truly "therapy-resistant asthma" is
      helpful and promotes a systematic consideration of contributory factors. Critical
      evaluation of factors contributing to difficult-to-manage asthma including
      adverse environment, comorbidities, nonadherence, and incorrect diagnosis is
      recommended in a systematic fashion in Part 1 of this contribution.

PMID- 22856632
TI  - Difficult asthma: assessment and management, Part 2.
AB  - Patients with severe asthma have considerable morbidity related to their asthma
      and are at risk for serious, life-threatening exacerbations. Their management
      requires an intensive and comprehensive approach, including attention to reducing
      exposure to environmental inciters of airway  inflammation and triggers of
      symptoms, patient education (including an asthma action plan), and opportunity
      for close patient-provider communication. Approved medical options include the
      lipoxygenase inhibitor, zileuton; the anti-immunoglobulin E monoclonal antibody,
      omalizumab; and bronchial  thermoplasty. Nonapproved interventions of potential
      benefit are ultrahigh-dose inhaled corticosteroids, anticholinergic
      bronchodilators (tiotropium), macrolide antibiotics, and vitamin D
      supplementation for the vitamin D-deficient patient. Potentially toxic, "steroid
      sparing"  therapies such as methotrexate, cyclosporine, and etanercept are best
      reserved for patients participating in clinical trials. Recognition of specific
      subtypes of patients with therapy-resistant asthma permits more targeted
      treatment approaches, such as for aspirin-sensitive asthma, persistent 
      eosinophilic asthma, asthma complicated by allergic bronchopulmonary
      aspergillosis, asthma with persistent airflow obstruction, and asthma with life
      threatening (near fatal) asthmatic attacks. Novel therapies based on an improved
      understanding of the pathobiology of therapy-resistant asthma  are greatly
      needed.

PMID- 22856633
TI  - MP29-02 (a novel intranasal formulation of azelastine hydrochloride and
      fluticasone propionate) in the treatment of seasonal allergic rhinitis: a
      randomized, double-blind, placebo-controlled trial of efficacy and safety.
AB  - Many patients with allergic rhinitis (AR) have uncontrolled symptoms despite
      available treatment options. This study was designed to evaluate the efficacy and
      safety of MP29-02 (a novel intranasal formulation of fluticasone propionate [FP]
      and azelastine [AZ] hydrochloride), compared with monotherapy with FP, AZ, and
      placebo sprays for the treatment of seasonal allergic rhinitis (SAR). This 2-week
      randomized, double-blind, placebo-controlled trial was conducted in 779 patients
      with moderate-to-severe SAR. Treatments were administered 1 spray/nostril twice
      daily in the same vehicle and delivery device. Daily doses of AZ and FP were 548
      and 200 micrograms, respectively. The primary efficacy variable was the 12-hour
      reflective total nasal symptom score (rTNSS), consisting of nasal congestion,
      sneezing, itchy nose, and runny nose. Secondary efficacy variables were (1) 12
      hour reflective individual nasal symptom scores; (2) onset of action; (3) 12-hour
      reflective total ocular symptom score (rTOSS), including itchy eyes, watery eyes,
      and red eyes; and (4) the Rhinoconjunctivitis Quality of Life Questionnaire
      (RQLQ) overall score. MP29-02 significantly reduced the mean rTNSS from baseline
      by -5.54 points compared with FP (-4.55; p = 0.038), AZ (-4.54; p = 0.032), and
      placebo (-3.03; p < 0.001), improving the rTNSS by 39% beyond the contribution of
      FP. All individual nasal symptoms contributed to the efficacy of MP29-02. Onset
      of action was within 30 minutes. MP29-02 significantly improved rTOSS compared
      with placebo, provided a clinically important improvement in the overall RQLQ
      score, and was well tolerated. In this study, MP29-02 provided more complete
      symptom relief than two widely used first-line AR treatments and was well
      tolerated.

PMID- 22856634
TI  - A study of IgE sensitization and skin response to histamine in Asian-Pacific
      American adults.
AB  - Allergic disorders and skin response to histamine have been noted to vary in
      different ethnicities. We investigated IgE-mediated allergic sensitization and
      skin response to histamine in Asian Pacific Americans (APAs), black and Hispanic
      Americans, and white adults. A retrospective questionnaire-based  study was
      performed of 2222 adults presenting at a New York City allergy referral center
      from 1994 to 2003. Questionnaire data included sex, age, and ethnicity and
      personal and family history of atopic disorders. Skin-prick test (SPT) data
      included saline and histamine controls and response  to a standardized panel of
      10 aeroallergens. APA patients had a lower odds of asthma (adjusted odds ratio
      [aOR], 0.68; 95% confidence interval [CI], 0.52-0.89; p = 0.005) and/or animal
      allergies (aOR, 0.64; 95% CI, 0.50-0.82; p = 0.0003). Histamine response was not
      significantly  different in APA (aOR, 0.90; 95% CI, 0.73-1.12; p = 0.36) or
      Hispanic Americans (aOR, 1.03; 95% CI, 0.85-1.24; p = 0.76), but was higher in
      black Americans (aOR, 2.32; 95% CI, 1.67-3.21; p < 0.0001). APA had higher odds
      of a positive SPT to trees (aOR, 1.49; 95% CI,  1.16-1.91; p = 0.002), grasses
      (aOR, 1.32; 95% CI, 1.05-1.43; p = 0.02), feathers (aOR, 1.65; 95% CI, 1.31-2.09;
      p < 0.0001), and cockroaches (aOR, 1.37; 95% CI, 1.10-1.62; p = 0.005). Moreover,
      APA had a higher total number of positive SPTs when compared with  white patients
      (5.5 +/- 3.2 versus 4.9 +/- 3.3; aOR, 1.34; 95% CI, 1.10-1.62 p = 0.004). APA
      adults in our patient population had more IgE sensitizations but not an increased
      skin response to histamine. In contrast, black Americans had increased skin
      response to histamine.

PMID- 22856635
TI  - Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent
      hereditary angioedema attacks.
AB  - Patients with hereditary angioedema (HAE) may have attacks triggered by dental,
      medical, or surgical procedures. This analysis evaluated the efficacy and safety
      of preprocedural administration of nanofiltered C1 esterase inhibitor (C1 INH-nf;
      human) for the prevention of HAE attacks during and after dental, medical, or
      surgical procedures. Data were reviewed retrospectively from two acute treatment
      trials in which at least 1000 U of C1 INH-nf was administered i.v. within 24
      hours before an emergency or noncosmetic medical, surgical, or dental procedure.
      Dosing data, HAE attacks reported within 72 hours, and adverse events (AEs)
      reported within 7 days after a preprocedural dose of C1 INH-nf were analyzed to
      assess efficacy and safety. Forty-one unique subjects (8 children and 33 adults)
      received C1 INH-nf for 91 procedures (40 in children and 51 in adults). The
      majority of procedures (56%) involved dental work and 44% involved a variety of
      surgical or medical procedures. A single 1000-U dose of C1 INH-nf was
      administered for 96% of procedures. An HAE attack did not occur within 72 hours
      after C1 INH-nf dosing for 98% (89/91) of procedures. Two HAE attacks were
      reported after the procedure, and both were treated with C1 INH-nf and achieved
      relief. None of the reported AEs were judged to be related to C1 INH-nf or were
      associated with an HAE attack. This analysis supports the efficacy and safety of
      preprocedural administration of C1 INH-nf for the prevention of HAE attacks.

PMID- 22856636
TI  - Treatment response after repeated administration of C1 esterase inhibitor for
      successive acute hereditary angioedema attacks.
AB  - Placebo-controlled studies established the efficacy of replacement therapy with
      C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary
      angioedema (HAE) attacks, but only limited data from prospective studies are
      available on repeated treatment of successive HAE attacks. This study evaluates
      the association between repeated treatments with 20 U/kg of C1-INH concentrate
      (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location
      and treatment response. In a post hoc analysis of an open-label extension study
      (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]),
      the association between repeated treatment with C1-INH and times to onset of
      symptom relief and complete resolution of HAE symptoms was assessed in patients
      who were treated for at least 15 attacks by linear regression on the ordinal
      attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE
      attacks over a mean duration of 34 months. Demographic and baseline
      characteristics of these patients were similar to those of all patients in the
      study. The distribution of body locations and the intensity of HAE attacks were
      similar for each of the first 15 attacks and subsequent attacks. The extent of
      previous use of C1-INH concentrate had no effect on the time to onset of symptom
      relief, the time to complete resolution of HAE symptoms, or the time between
      attacks treated with C1-INH concentrate; the median of individual linear
      regression coefficients was not statistically significantly different from 0.
      Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment
      response in patients treated for multiple successive HAE attacks at any body
      location. (Clinicaltrials.gov identifier: NCT00292981).

PMID- 22856637
TI  - Salivary cortisol monitoring: determination of reference values in healthy
      children and application in asthmatic children.
AB  - Venipuncture testing of adrenocortical function in asthmatic infants and young
      children receiving inhaled corticosteroids can raise cortisol levels and mask
      physiological responses. This study aimed to establish reference ranges for
      salivary cortisol levels and evaluate the safety and effects of jet-nebulized
      budesonide inhalation suspension (BIS) on salivary cortisol levels and patient
      outcomes in infants and young children with mild or persistent asthma. Reference
      salivary cortisol levels were determined in healthy children aged 6 months to 4
      years old. A 12-week multicenter, randomized, parallel-group, open-label study
      was performed involving 53 age-matched asthmatic children who received either 0.5
      mg/day of BIS or 40-60 mg/day of cromolyn sodium inhalation suspension (CIS) via
      compressor nebulizer. The effective measuring range of salivary cortisol
      concentration in asthmatic children was 0.12-3.00 micrograms/dL. The upper and
      lower limits of the reference range were 0.827 and 0.076 micrograms/dL,
      respectively. No significant difference was seen from baseline through week 12 in
      the CIS and BIS groups. BIS was safe in these patients, with no inhibitory
      effects on adrenocortical function. Salivary cortisol measurement offers a useful
      and accurate tool for testing adrenocortical function in infants and young
      children. Longer-term studies that incorporate testing of the hypothalamic
      pituitary-adrenal axis are warranted to confirm our findings.

PMID- 22856638
TI  - Allergy consult for eosinophilia in an infant.
AB  - Specialists in allergy/immunology are often asked to evaluate patients with
      eosinophilia, with the general assumption of an underlying allergic or
      immunologic disease. We present a case of an infant referred for marked
      eosinophilia. Although atopic disease may be in the differential  diagnosis, it
      is rarely associated with hypereosinophilia, and other conditions need to be
      investigated. Until the underlying cause is identified, systemic corticosteroid
      therapy may be initiated, mainly in severe cases.

PMID- 22856639
TI  - Molecular simulation of fibronectin adsorption onto polyurethane surfaces.
AB  - Poly(ethylene glycol)-based polyurethanes have been widely used in biomedical
      applications; however, they are prone to swelling. A natural polyol, castor oil,
      can be incorporated into these polyurethanes to control the degree of the
      swelling, which alters mechanical properties and protein adsorption
      characteristic of the polymers. In this work, we modeled poly(ethylene glycol)
      and castor oil copolymers of hexamethylene diisocyanate-based polyurethanes (PEG
      HDI and CO-HDI, respectively) and compared their mechanisms for fibronectin
      adsorption using molecular mechanics and molecular dynamics simulations. Results
      showed that the interplay between the hydrophobic residues concentrated at the N
      terminal end of the protein, the surface roughness, and the hydrophilicity of the
      polymer surface determine the overall protein adsorption affinity. Incorporating
      explicit water molecules in the simulations results in higher affinity for
      fibronectin adsorption to more hydrophobic surface of CO-HDI surfaces,
      emphasizing the role that water molecules play during adsorption. We also
      observed that the strain energies that are indicative of flexibility and
      consequently entropy are significantly affected by the changes in the patterns of
      beta-sheet formation/breaking. Our study lends supports to the view that while
      castor oil controls the degree of swelling, it increases the adsorption of
      fibronectin to a limited extent due to the interplay between its hydrophobicity
      and its surface roughness, which needs to be taken into account during the design
      of polyurethane-based biomaterials.

PMID- 22856640
TI  - Degradation of biodegradable plastic mulch films in soil environment by
      phylloplane fungi isolated from gramineous plants.
AB  - To improve the biodegradation of biodegradable plastic (BP) mulch films, 1227
      fungal strains were isolated from plant surface (phylloplane) and evaluated for
      BP-degrading ability. Among them, B47-9 a strain isolated from the leaf surface
      of barley showed the strongest ability to degrade poly-(butylene succinate-co
      butylene adipate) (PBSA) and poly-(butylene succinate) (PBS) films. The strain
      grew on the surface of soil-mounted BP films, produced breaks along the direction
      of hyphal growth indicated that it secreted a BP-degrading enzyme, and has
      directly contributing to accelerating the degradation of film. Treatment with the
      culture filtrate decomposed 91.2 wt%, 23.7 wt%, and 14.6 wt% of PBSA, PBS, and
      commercially available BP polymer blended mulch film, respectively, on
      unsterlized soil within 6 days. The PCR-DGGE analysis of the transition of soil
      microbial community during film degradation revealed that the process was
      accompanied with drastic changes in the population of soil fungi and Acantamoeba
      spp., as well as the growth of inoculated strain B47-9. It has a potential for
      application in the development of an effective method for accelerating
      degradation of used plastics under actual field conditions.

PMID- 22856641
TI  - New nebulizer technology to monitor adherence and nebulizer performance in cystic
      fibrosis.
AB  - Topical delivery of aerosolized therapies is an established treatment for chronic
      airway infection and inflammation in cystic fibrosis (CF). Recent developments in
      nebuliser technology have enabled Adaptive Aerosol Delivery (AAD) of mesh
      generated aerosol particles resulting in more efficient airway deposition than
      existing jet nebulizers. An additional feature of these new devices is the
      ability to record and examine the performance of the device by downloading stored
      data (electronic data capture). In a series of studies we have used this
      downloading facility to monitor treatment times and examine adherence to
      nebulizer therapy in our pediatric patients. We found routine adherence
      monitoring is possible in busy CF clinic. We have shown that good adherence to
      treatment can be maintained in both patients chronically infected with
      Pseudomonas aeruginosa on long-term therapy, and in patients with first/new
      growths of Pseudomonas on short-term eradication therapy. When adherence was
      examined from an individual perspective, we demonstrated a wide variation both
      between and within individual patients. A further modification of AAD technology,
      Target Inhalation Mode (TIM) optimises patient inhalations through a direct
      feedback mechanism. This new breathing mode has also been evaluated in our
      pediatric CF clinic in a recent randomized controlled trial (RCT) and we have
      shown that children maintain adherence to treatment through the TIM mouthpiece
      and average treatment times reduced from 6.9 to 3.7 min when using TIM. This is a
      new era of aerosol delivery and novel advances in medical devices need to be
      monitored and assessed rigorously, particularly as new and potentially expensive
      therapies emerge from translational studies. Electronic data capture enables CF
      teams to work in an open partnership with patients to achieve the common goals of
      improving drug delivery and reducing patient burden.

PMID- 22856643
TI  - Social, psychological, and environmental-structural factors determine consistent
      condom use among rural-to-urban migrant female sex workers in Shanghai China.
AB  - BACKGROUND: To determine potential social, psychological, and environmental
      structural factors that may result in motivating female sex workers (FSWs), who
      are rural-to-urban migrants, and their paying partners in Shanghai, China to
      promote consistent condom use (CCU). METHODS: A cross-sectional study was
      conducted in five districts of Shanghai, including three suburbs and two downtown
      locales. We adopted a cluster randomized sampling method to obtain 20 geographic
      sites, which consisted of 1 or more communities/villages proximal to a location
      where FSWs were accessible. Five hundred four FSWs from 132 Xitou Fang (shampoo
      wash rooms), massage parlors, and hair salons who explicitly provided sexual
      services were enrolled in the study. Each participant completed a questionnaire
      survey and interview aimed to collect information on the perceptions and
      behaviors of individuals associated with a risk for human immunodeficiency
      virus/acquired immunodeficiency syndrome(HIV/AIDS),self-efficacy at negotiating
      safe sex,and the physical, social, and policy environment of the establishments
      where they worked. RESULTS: The percentage of FSWs who reported consistent condom
      use with their paying partners was 63.3%. Controlling for socio-demographic
      characteristics in multivariate analyses, environmental-structural support (OR,
      3.96; CI, 2.52-6.22) for condom use was the most significant positive predictor
      of CCU among FSWs and their regular paying partners. A high perception of
      susceptibility and risk of HIV/AIDS (OR, 1.96; CI, 1.25-3.01), a high perception
      of benefits on condom use to protect themselves (OR, 2.06; CI, 1.32-3.22), and
      high safe sex self-efficacy (OR, 2.52; CI, 1.64-3.85) also play important roles
      on CCU based on multivariate analyses. CONCLUSIONS: Environmental-structural
      factor support for condom use, in addition to social, psychological, and
      individual cognitive factors are significant predictors of CCU among FSWs, which
      should be assessed and addressed in research and interventions related to
      HIV/AIDS prevention among FSWs in China.

PMID- 22856644
TI  - Selective sidewall wetting of polymer blocks in hydrogen silsesquioxane directed
      self-assembly of PS-b-PDMS.
AB  - We show the importance of sidewall chemistry for the graphoepitaxial alignment of
      PS-b-PDMS using prepatterns fabricated by electron beam lithography of hydrogen
      silsesquioxane (HSQ) and by deep ultraviolet (DUV) lithography on SiO(2) thin
      films. Density multiplication of polystyrene-block-polydimethylsiloxane (PS-b
      PDMS) within both prepatterns was achieved by using a room temperature dynamic
      solvent annealing environment. Selective tuning of PS and PDMS wetting on the HSQ
      template sidewalls was also achieved through careful functionalization of the
      template and substrate surface using either brush or a self-assembled
      trimethylsilyl monolayer. PDMS selectively wets HSQ sidewalls treated with a
      brush layer of PDMS, whiereas PS is found to selectively wet HSQ sidewalls
      treated with hexamethyldisilazane (HMDS) to produce a trimethylsilyl-terminated
      surface. The etch resistance of the aligned polymer was also evaluated to
      understand the implications of using block copolymer patterns which have high
      etch resistance, self-forming (PDMS) wetting layers at both interfaces. The
      results outlined in this work may have direct applications in nanolithography for
      continued device scaling toward the end-of-roadmap era.

PMID- 22856645
TI  - Larval food quantity affects development time, survival and adult biological
      traits that influence the vectorial capacity of Anopheles darlingi under
      laboratory conditions.
AB  - BACKGROUND: The incidence of malaria in the Amazon is seasonal and mosquito
      vectorial capacity parameters, including abundance and longevity, depend on
      quantitative and qualitative aspects of the larval diet. Anopheles darlingi is a
      major malaria vector in the Amazon, representing >95% of total Anopheles
      population present in the Porto Velho region. Despite its importance in the
      transmission of the Plasmodium parasite, knowledge of the larval biology and
      ecology is limited. Studies regarding aspects of adult population ecology are
      more common than studies on larval ecology. However, in order develop effective
      control strategies and laboratory breeding conditions for this species, more data
      on the factors affecting vector biology is needed. The aim of the present study
      is to assess the effects of larval food quantity on the vectorial capacity of An.
      darling under laboratory conditions. METHODS: Anopheles darlingi was maintained
      at 28 degrees C, 80% humidity and exposed to a daily photoperiod of 12 h. Larvae
      were divided into three experimental groups that were fed either a low, medium,
      or high food supply (based on the food amounts consumed by other species of
      culicids). Each experiment was replicated for six times. A cohort of adults were
      also exposed to each type of diet and assessed for several biological
      characteristics (e.g. longevity, bite frequency and survivorship), which were
      used to estimate the vectorial capacity of each experimental group. RESULTS: The
      group supplied with higher food amounts observed a reduction in development time
      while larval survival increased. In addition to enhanced longevity, increasing
      larval food quantity was positively correlated with increasing frequency of
      bites, longer blood meal duration and wing length, resulting in greater vectorial
      capacity. However, females had greater longevity than males despite having
      smaller wings. CONCLUSIONS: Overall, several larval and adult biological traits
      were significantly affected by larval food availability. Greater larval food
      supply led to enhance larval and production and larger mosquitoes with longer
      longevity and higher biting frequency. Thus, larval food availability can alter
      important biological traits that influence the vectorial capacity of An.
      darlingi.

PMID- 22856646
TI  - The p53 codon 72 polymorphism and the risk of oral cancer in a Chinese Han
      population.
AB  - BACKGROUND: The p53 codon 72 polymorphism has been investigated extensively for
      its association with various cancers around the world. It is still unclear
      whether the p53 codon 72 polymorphism is associated with oral cancer risk. AIM:
      The aim of our study was to evaluate the association between the p53 codon 72
      polymorphism and the oral cancer risk in Chinese Han patients. METHODS: A
      hospital-based case-control study with 200 patients with oral cancer and 200
      matched controls was conducted. Genomic DNA was isolated from peripheral blood,
      and gene polymorphisms were analyzed by polymerase chain reaction-restriction
      fragment length polymorphism. RESULTS: The arginine (Arg)/Arg genotype conferred
      0.57 times reduced risk to oral cancer (95% confidence interval [CI]=0.36, 0.89;
      p=0.01). The Arg allele frequency was significantly lower (odds ratios [OR]=0.74,
      95% CI=0.56, 0.98; p=0.03) in comparison with controls in patients with oral
      cancer. The proline allele frequency was significantly higher (OR=1.35, 95%
      CI=1.02, 1.79; p=0.03) in comparison with controls in patients with oral cancer.
      When stratified by the clinical stage, lymph node metastasis, and histological
      differentiation of oral cancer, no statistically significant results were
      observed. CONCLUSION: Our results thus suggest that the p53 codon 72 polymorphism
      modulates susceptibility to oral cancer in Chinese Han patients.

PMID- 22856647
TI  - Synthesis of the silaisocyanoacetylene molecule.
AB  - The hitherto elusive silaisocyanoacetylene molecule (HCCNSi)-a member of the
      silaisocyanide family-has been synthesized for the first time through the
      reaction of the silicon nitride radical (SiN) with acetylene (C(2)H(2)) in the
      gas phase under single collision conditions. Compared to the isoelectronic
      reaction of the cyano radical (CN) with acetylene, the replacement of the carbon
      atom in the cyano group by an isovalent silicon atom has a pronounced effect on
      the reactivity. Whereas the silicon nitride radical was found to pass an entrance
      barrier and adds with the nitrogen atom to the acetylene molecule, the cyano
      radical adds barrierlessly with the carbon atom forming the HCCH(NSi) and
      HCCH(CN) intermediates, respectively. These structures undergo hydrogen loss to
      form the linear silaisocyanoacetylene (HCCNSi) and cyanoacetylene molecules
      (HCCCN), respectively. Therefore, the isovalency of the silicon atom was found to
      bear little resemblance with the carbon atom having a dramatic effect not only on
      the reactivity, but also on the reaction mechanism, thermochemistry, and chemical
      bonding of the isoelectronic silaisocyanoacetylene and cyanoacetylene products,
      effectively reversing the thermodynamical stability of the nitrile versus
      isonitrile and silanitrile versus isosilanitrile isomer pairs.

PMID- 22856648
TI  - The bond of different post materials to a resin composite cement and a resin
      composite core material.
AB  - PURPOSE: To investigate the bond of endodontic post materials, with and without
      grit blasting, to a resin composite cement and a core material using push-out
      bond strength tests. MATERIALS AND METHODS: Fiber-reinforced composite (FRC)
      posts containing carbon (C) or glass (A) fiber and a steel (S) post were cemented
      into cylinders of polymerized restorative composite without surface treatment (as
      controls) and after grit blasting for 8, 16, and 32 seconds. Additional steel
      post samples were sputter-coated with gold before cementation to prevent chemical
      interaction with the cement. Cylindrical composite cores were bonded to other
      samples. After sectioning into discs, bond strengths were determined using push
      out testing. Profilometry and electron microscopy were used to assess the effect
      of grit blasting on surface topography. RESULTS: Mean (standard deviation) bond
      strength values (MPa) for untreated posts to resin cement were 8.41 (2.80) for C,
      9.61(1.88) for A, and 19.90 (3.61) for S. Prolonged grit blasting increased bond
      strength for FRC posts but produced only a minimal increase for S. After 32
      seconds, mean values were 20.65 (4.91) for C, 20.41 (2.93) for A, and 22.97
      (2.87) for S. Gold-coated steel samples produced the lowest bond strength value,
      7.84 (1.40). Mean bond strengths for untreated posts bonded to composite cores
      were 6.19 (0.95) for C, 13.22 (1.61) for A, and 8.82 (1.18) for S, and after 32
      seconds of grit blasting the values were 17.30 (2.02) for C, 26.47 (3.09) for A,
      and 20.61 (2.67) for S. FRC materials recorded higher roughness values before and
      after grit blasting than S. With prolonged grit blasting, roughness increased for
      A and C, but not for S. CONCLUSIONS: There was no evidence of significant bonding
      to untreated FRC posts, but significant bonding occurred between untreated steel
      posts and the resin cement. Increases in the roughness of FRC samples were
      material dependent and roughening significantly increased bond strength values
      (p<0.05). Surface roughening of the tested FRC posts is required for effective
      bonding.

PMID- 22856649
TI  - A resource for benchmarking the usefulness of protein structure models.
AB  - BACKGROUND: Increasingly, biologists and biochemists use computational tools to
      design experiments to probe the function of proteins and/or to engineer them for
      a variety of different purposes. The most effective strategies rely on the
      knowledge of the three-dimensional structure of the protein of interest. However
      it is often the case that an experimental structure is not available and that
      models of different quality are used instead. On the other hand, the relationship
      between the quality of a model and its appropriate use is not easy to derive in
      general, and so far it has been analyzed in detail only for specific application.
      RESULTS: This paper describes a database and related software tools that allow
      testing of a given structure based method on models of a protein representing
      different levels of accuracy. The comparison of the results of a computational
      experiment on the experimental structure and on a set of its decoy models will
      allow developers and users to assess which is the specific threshold of accuracy
      required to perform the task effectively. CONCLUSIONS: The ModelDB server
      automatically builds decoy models of different accuracy for a given protein of
      known structure and provides a set of useful tools for their analysis. Pre
      computed data for a non-redundant set of deposited protein structures are
      available for analysis and download in the ModelDB database. IMPLEMENTATION,
      AVAILABILITY AND REQUIREMENTS: Project name: A resource for benchmarking the
      usefulness of protein structure models. Project home page:
      http://bl210.caspur.it/MODEL-DB/MODEL-DB_web/MODindex.php.Operating system(s):
      Platform independent. Programming language: Perl-BioPerl (program); mySQL, Perl
      DBI and DBD modules (database); php, JavaScript, Jmol scripting (web server).
      Other requirements: Java Runtime Environment v1.4 or later, Perl, BioPerl, CPAN
      modules, HHsearch, Modeller, LGA, NCBI Blast package, DSSP, Speedfill (Surfnet)
      and PSAIA. License: Free. Any restrictions to use by non-academics: No.

PMID- 22856650
TI  - Modelling the effects of maternal socio-demographic characteristics on the
      preterm and term birth weight distributions in Greece using quantile regression.
AB  - The present study aims at modelling the effects of maternal socio-demographic
      characteristics on the birth weight distribution in Greece. The analysis is based
      on nationwide vital registration micro-data; 103,266 single live births recorded
      in 2006 are considered. Quantile regression models, allowing for the effects of
      covariates to vary across the conditional distribution of the dependent variable,
      birth weight, are applied to preterm and term births separately. The statistical
      analysis shows that the effects of most factors differentiate across the birth
      weight distributions. Ordinary Least Squares (OLS) coefficients, on the other
      hand, systematically underestimate effects at the lower tail and overestimate
      effects among heavier babies. Hence, quantile regression has a strong advantage
      over the OLS method. The findings also indicate that birth weight distributions
      of term and preterm infants are distinct and should be analysed separately. For
      both distributions female sex, primiparity, age of mother over 35 and prior
      history of stillbirths and child deaths are related to lower birth weight while
      higher educational attainment has a protective effect. Among term births,
      illegitimacy, living in big metropolitan areas and immigrant status of the mother
      are also significant predictors. For preterm births the impact of age of mother,
      parity and, in particular, prior stillbirths or deceased children is very
      pronounced.

PMID- 22856651
TI  - Association between serum endogenous secretory receptor for advanced glycation
      end products and risk of type 2 diabetes mellitus with combined depression in the
      Chinese population.
AB  - OBJECTIVE: The role of the endogenous secretory receptor for advanced glycation
      end products (esRAGE) in depression of diabetes patients and its clinical
      significance are unclear. This study investigated the role of serum esRAGE in
      patients with type 2 diabetes mellitus with depression in the Chinese population.
      PATIENTS AND METHODS: One hundred nineteen hospitalized patients with type 2
      diabetes were recruited at Fujian Provincial Hospital (Fuzhou, China) from
      February 2010 to January 2011. All selected subjects were assessed with the
      Hamilton Rating Scale for Depression (HAMD). Among them, 71 patients with both
      type 2 diabetes and depression were included. All selected subjects were examined
      for the following: esRAGE concentration, glycosylated hemoglobin (HbA1c), blood
      lipids, C-reactive protein, trace of albumin in urine, and carotid artery intima
      media thickness (IMT). Association between serum esRAGE levels and risk of type 2
      diabetes mellitus with depression was also analyzed. RESULTS: There were
      statistically significant differences in gender, age, body mass index, waist
      circumference, and treatment methods between the group with depression and the
      group without depression (P<0.05). Multiple linear regression analysis showed
      that HAMD scores were negatively correlated with esRAGE levels (standard
      regression coefficient -0.270, P<0.01). HAMD-17 scores were positively correlated
      with IMT (standard regression coefficient 0.183, P<0.05) and with HbA1c (standard
      regression coefficient 0.314, P<0.01). CONCLUSIONS: Female gender, younger age,
      obesity, poor glycemic control, complications, and insulin therapy are all risk
      factors of type 2 diabetes mellitus with combined depression in the Chinese
      population. Inflammation and atherosclerosis play an important role in the
      pathogenesis of depression. esRAGE is a protective factor of depression among
      patients who have type 2 diabetes.

PMID- 22856652
TI  - Use of UV-C radiation to disinfect non-critical patient care items: a laboratory
      assessment of the Nanoclave Cabinet.
AB  - BACKGROUND: The near-patient environment is often heavily contaminated, yet the
      decontamination of near-patient surfaces and equipment is often poor. The
      Nanoclave Cabinet produces large amounts of ultraviolet-C (UV-C) radiation (53
      W/m2) and is designed to rapidly disinfect individual items of clinical
      equipment. Controlled laboratory studies were conducted to assess its ability to
      eradicate a range of potential pathogens including Clostridium difficile spores
      and Adenovirus from different types of surface. METHODS: Each test surface was
      inoculated with known levels of vegetative bacteria (10(6) cfu/cm(2)), C.
      difficile spores (10(2)-10(6) cfu/cm(2)) or Adenovirus (10(9) viral genomes),
      placed in the Nanoclave Cabinet and exposed for up to 6 minutes to the UV-C light
      source. Survival of bacterial contaminants was determined via conventional
      cultivation techniques. Degradation of viral DNA was determined via PCR. Results
      were compared to the number of colonies or level of DNA recovered from non
      exposed control surfaces. Experiments were repeated to incorporate organic soils
      and to compare the efficacy of the Nanoclave Cabinet to that of antimicrobial
      wipes. RESULTS: After exposing 8 common non-critical patient care items to two 30
      second UV-C irradiation cycles, bacterial numbers on 40 of 51 target sites were
      consistently reduced to below detectable levels (>= 4.7 log10 reduction).
      Bacterial load was reduced but still persisted on other sites. Objects that
      proved difficult to disinfect using the Nanoclave Cabinet (e.g. blood pressure
      cuff) were also difficult to disinfect using antimicrobial wipes. The efficacy of
      the Nanoclave Cabinet was not affected by the presence of organic soils.
      Clostridium difficile spores were more resistant to UV-C irradiation than
      vegetative bacteria. However, two 60-second irradiation cycles were sufficient to
      reduce the number of surface-associated spores from 10(3) cfu/cm(2) to below
      detectable levels. A 3 log10 reduction in detectable Adenovirus DNA was achieved
      within 3 minutes; after 6 minutes, viral DNA was undetectable. CONCLUSION: The
      results of this study suggest that the Nanoclave Cabinet can provide rapid and
      effective disinfection of some patient-related equipment. However, laboratory
      studies do not necessarily replicate 'in-use' conditions and further tests are
      required to assess the usability, acceptability and relative performance of the
      Nanoclave Cabinet when used in situ.

PMID- 22856654
TI  - Role of reactive oxygen species in cocaine-induced target organ dysfunction.
      Mechanisms of action and therapeutic perspectives.

PMID- 22856653
TI  - IL-1 generated subsequent to radiation-induced tissue injury contributes to the
      pathogenesis of radiodermatitis.
AB  - Radiation injury in the skin causes radiodermatitis, a condition in which the
      skin becomes inflamed and the epidermis can break down. This condition causes
      significant morbidity and if severe it can be an independent factor that
      contributes to radiation mortality. Radiodermatitis is seen in some settings of
      radiotherapy for cancer and is also of concern as a complication post-radiation
      exposure from accidents or weapons, such as a "dirty bomb". The pathogenesis of
      this condition is incompletely understood. Here we have developed a murine model
      of radiodermatitis wherein the skin is selectively injured by irradiation with
      high-energy electrons. Using this model we showed that the interleukin-1 (IL-1)
      pathway plays a significant role in the development of radiodermatitis. Mice that
      lack either IL-1 or the IL-1 receptor developed less inflammation and less severe
      pathological changes in their skin, especially at later time-points. These
      findings suggest that IL-1 pathway may be a potential therapeutic target for
      reducing the severity of radiodermatitis.

PMID- 22856655
TI  - Data available on the extent of cocaine use and dependence: biochemistry,
      pharmacologic effects and global burden of disease of cocaine abusers.
AB  - Drug use is seen more as an individualistic behaviour and is therefore not
      readily conceived of from a population perspective. There is general recognition
      of several phases and degrees of drug abuse, from initiation and early-use
      patterns to long-term chronic use. Cocaine and its derivative "crack" cocaine
      provide an example of both the globalization of substance use and the cyclical
      nature of drug epidemics. Cocaine is a powerful CNS (Central Nervous System)
      stimulant but exerts its action in a several types of adverse health effects,
      including acute toxic effects (i.e. overdose, accidental injury and violence),
      dependence, cardiovascular disease, cirrhosis, bloodborne bacterial and viral
      infections, and mental disorders. Of interest, many people who use Cocaine will
      use also other drugs; therefore, ascribing adverse health effect to a certain
      drug might be difficult. Any mucous membrane can act as a port of entry for
      cocaine and the systemic effect is greatly influenced by the route and speed of
      administration. The effects of Cocaine mainly depend on the user's addiction, the
      dose received and the mode of assumption. Laws restricting the availability of
      cocaine saw a decrease in consumption in these countries until the 1960s. The
      number of cocaine users worldwide ranged from 14 million to 21 million (0.3-0.5%
      of the population aged 15-64 years). The largest market was North America, then
      western and central Europe and South America.

PMID- 22856656
TI  - Neuropathological alterations in cocaine abuse.
AB  - Cocaine abuse represents a significant health issue worldwide. Besides
      cardiovascular complications, psychiatric and neurologic symptoms are the most
      common manifestations of cocaine toxicity. In cocaine abusers brain abnormalities
      have been shown with computed tomography (CT), magnetic resonance imaging (MRI),
      positron emission tomography (PET), or single photon emission computed tomography
      (SPECT). The spectrum of neuropathologic alterations seen in cocaine abusers is
      broad. The major findings consist of vascular complications such as stroke,
      subarachnoid and intracerebral hemorrhages and cerebral ischemia. Persons with
      underlying arteriovenous malformation or aneurysm are especially prone for such
      events. Except for a few incidents of vasculitis, the etiology of cocaine-
      related cerebrovascular events is still unclear. Cocaine-induced vasospasm,
      impaired hemostasis and platelet function, as well as decreased cerebral blood
      flow, have been proposed as possible mechanisms. On the molecular level,
      alterations in the expression of transcription factors and changes of brain
      neurotransmitter systems have been reported.

PMID- 22856657
TI  - Cardiovascular effects of cocaine: cellular, ionic and molecular mechanisms.
AB  - Cocaine is a widely abused drug responsible for the majority of deaths ascribed
      to drug overdose. Many mechanisms have been proposed in order to explain the
      various cocaine associated cardiovascular complications. Conventionally, cocaine
      cardiotoxicity has been thought to be mediated indirectly through its
      sympathomimetic effect, i.e., by inhibiting the reuptake and thus increasing the
      levels of neuronal catecholamines at work on adrenoceptors. Increased oxidative
      stress, reactive oxygen species, and cocaine-induced apoptosis in the heart
      muscle have suggested a new way to understand the cardiotoxic effects of cocaine.
      More recent studies have led the attention to the interaction of cocaine and some
      metabolites with cardiac sodium, calcium and potassium channels. The current
      paper is aimed to investigate the molecular mechanisms of cocaine cardiotoxicity
      which have a specific clinical and forensic interest. From a clinical point of
      view the full knowledge of the exact mechanisms by which cocaine exerts cardio -
      vascular damage is essential to identify potential therapeutic targets and
      improve novel strategies for cocaine related cardiovascular diseases. From a
      forensic point of view, it is to be underlined that cocaine use is often
      associated to sudden death in young, otherwise healthy individuals. While such
      events are widely reported, the relationship between cardiac morphological
      alterations and molecular/cellular mechanisms is still controversial. In
      conclusion, the study of cocaine cardiovascular toxicity needs a strict
      collaboration between clinicians and pathologists which may be very effective in
      further dissecting the mechanisms underlying cocaine cardiotoxicity and
      understanding the cardiac cocaine connection.

PMID- 22856658
TI  - Cocaine toxicity and hepatic oxidative stress.
AB  - Cocaine belongs to the group of psychostimulants and together with amphetamines
      has been recognized as one of the most significant examples of drug abuse.
      Cocaine abuse is due to intense feelings of euphoria, friendliness, empathy, and
      hyperactivity, which result from its potent inhibitory effects on presynaptic
      dopamine and noradrenaline re-uptake. Misuse of cocaine can induce severe toxic
      effects, including neurotoxicity, cardiotoxicity, hepatotoxicity. There are a
      number of data, both experimental and clinical, regarding its hepatotoxic
      effects, associated with lipid peroxidation-induced oxidative damage. The
      oxidative metabolism of cocaine to reactive oxygen species (ROS) like nitrogen
      peroxide and superoxide anion radicals are thought to be responsible for the
      cocaine associated liver injury. This review summarizes the present information
      on cocaine hepatic biotransformation and the possible role of its oxidative
      metabolism in cocaine-induced hepatic injury.

PMID- 22856659
TI  - Contribution of oxidative metabolism to cocaine-induced liver and kidney damage.
AB  - Cocaine is a potent psychoactive illicit substance and its abuse represents a
      major health burden worldwide. The pharmacodynamics and toxicity of cocaine have
      been extensively documented, and are generally associated to its affinity towards
      neurotransmitters transporters and several receptors. However, drug-related
      formation of reactive compounds, as is the case of pro-oxidant reactive species,
      and interaction at molecular level is still an understudied matter. The
      involvement of oxidative stress (OS) in cocaine-induced toxicity has been
      reported in both human and animal models, in several organs and systems,
      including heart, liver, kidney, and central nervous system (CNS). Cytochrome P450
      (CYP450)-mediated cocaine metabolism yields the reactive pro-oxidant compound
      norcocaine (NCOC) and further oxidative metabolites. Special emphasis should be
      given to the stable radical norcocaine nitroxide (NCOC-NO.), which plays a key
      role in cocaine-induced hepatotoxicity, either by entering a futile redox cycle
      with an N-oxidative metabolite, or by being further oxidized to a highly reactive
      ion. In fact, cocaine-induced generation of reactive oxygen species (ROS) and
      consequent OS has been postulated based on the reactivity of cocaine N-oxidative
      metabolites. Depletion of cellular antioxidant defenses and impairment of
      mitochondrial respiration have also been considered important causes of ROS
      production, and subsequent cell death mediated by cocaine. The present review
      provides a thorough description of the current knowledge on cocaine oxidative
      metabolism and its role on drug-induced liver and kidney damage.

PMID- 22856660
TI  - Toxicokinetics of cocaine and metabolites: the forensic toxicological approach.
AB  - Cocaine is one of the most used psychomotor stimulants all over the world. On
      this basis, the interest for the pharmacological activity and the pharmacodynamic
      and pharmacokinetic aspects of this drug is very prominent in both clinical and
      forensic toxicological environments. The review presents and discusses 65
      scientific publications covering all the aspects of cocaine toxicokinetic,
      including absorption, distribution, metabolism and elimination of the drug.
      Particular attention has been dedicated to the studies on the disposition of the
      drug in alternative biological matrices, such as oral fluid, hair, fetus fluids
      and tissues, and sweat. In fact, in the last years the use of these matrices has
      been proposed in clinical and forensic drug analysis in order to obtain
      additional information to that which can be obtained by analyzing the traditional
      biological matrices, such as blood and urine.

PMID- 22856661
TI  - Diagnosis and consequences of cocaine addiction.
AB  - Cocaine remains the second most commonly used and trafficked illicit drug in the
      world after cannabis. This psychostimulant drug has become an essential part of
      the world drug scene with a different use among countries. Prevalence of cocaine
      use (lifetime, last year, last month use) is particulary high among males aged
      between 15 and 34 years. Five per cent of cocaine users will develop a substance-
      dependence during the first year of use, and 20% of these will become long-term
      cocaine-dependent patients. The number of patients entering drug treatment for
      primary cocaine use has been increasing in Europe for several years. Cocaine
      addiction is a worldwide public health problem, which has somatic, psychological,
      psychiatric, socio-economic and judicial complications. This article aims to
      provide the clinician with a detailed description of the clinical aspects, the
      adverse effects and the complications of cocaine addiction. Literature searches
      were conducted for the period from January 1985 to February 2012 using PubMed,
      EMBASE, PsycInfo, and Google Scholar.

PMID- 22856662
TI  - Role of oxidative stress in cocaine-induced cardiotoxicity and cocaine-related
      death.
AB  - Cocaine-induced cardiovascular disorders such as hypertension, thrombosis,
      myocardial dysfunction, cardiac dysrhythmias and endocarditis have received
      widespread attention in the context of cocaine abuse. The number of sudden deaths
      from cardiac causes, including myocardial infarction, ventricular tachyarrhythmia
      or aortic dissection, is also increasing. This manuscript will highlight the
      recent employment of study about cocaine cardiotoxicity and oxidative stress.
      Evidence has revealed that cardiac oxidative stress is a prominent early event of
      cocaine administration, which severely compromises the cardiac antioxidant
      cellular system and causes cardiac antioxidant cellular system injuries.
      Oxidative damage such as peroxidation of membrane phospholipids and depletion of
      nonenzymatic antioxidants such as glutathione have been found in the myocardium
      of chronic cocaine-treated animals and in patients. The data indicate that
      cocaine administration compromised the heart's antioxidant defense system. About
      the mechanisms involved in the cellular damage, the evidence that cocaine causes
      apoptosis in the heart comes from in vivo study. In animals model after short
      term and long term-cocaine administration, the investigators demonstrates the
      role of Reactive Oxygen Species as a trigger of cardiac injury induced by
      cocaine. Cocaine also increased infiltration of inflammatory cells in the heart,
      and apoptotic cells were predominantly found near inflammatory cells. The role of
      oxidative stress in cocaine-induced apoptosis in the heart is wide studied and
      documented.

PMID- 22856663
TI  - Targeting Bcl-2 in CLL.
AB  - Chronic lymphocytic leukemia (CLL) is a common adult leukemia in the Western
      world with an incidence of 4.2/100,000/year. The clinical course of disease is
      highly heterogenous; it affects people over 65-70 years of age. This hematologic
      cancer is characterized by the resistance to apoptosis stimuli predominantly
      associated with overexpression of antiapoptotic Bcl-2 family members. Therapeutic
      options for advanced CLL patients are limited. Thus there is an urgent need to
      discover a novel, less toxic, and much more effective agent(s) or drug
      combinations for CLL patients. Among chemotherapeutic(s) and immunotherapeutics
      currently in use, several enzyme inhibitors were tested to gain better results in
      CLL treatment. Here, we review the main achievements made on targeting of
      prosurvival Bcl-2 proteins through the use of different approaches, i.e. anti
      sense methodology, small molecules that mimic the action of BH3 domain and
      microRNAs (mainly miRNA-15a and miRNA-16-1).

PMID- 22856664
TI  - Induction of apoptosis in macrophages via Kv1.3 and Kv1.5 potassium channels.
AB  - We have previously shown that the mitochondrial potassium channel Kv1.3 (mtKv1.3)
      in T lymphocytes is a novel target of Bax. Mutation of Bax at lysine 128
      (BaxK128E) abrogates its inhibitory effects on mtKv1.3 and prevents apoptosis.
      The importance of mtKv1.3 inhibition was underscored by the finding that membrane
      permeant Kv1.3 inhibitors induced Bax/Bak-independent cell death and reduced the
      volume of an mtKv1.3-expressing tumor by 90% in a mouse model. However, the
      possible involvement of other Kv channels in apoptosis has not been clarified.
      Here we report that, like Kv1.3, Kv1.1 and Kv1.5 also interact with Bax.
      Transfection of Kvdeficient lymphocytes with Kv1.1 restores sensitivity to cell
      death in apoptosis-resistant CTLL-2 lymphocytes. SiRNA down-regulation of Kv1.3
      and Kv1.5 expression in macrophages confers resistance to apoptosis. We further
      report that J774 macrophages express Kv1.3 and Kv1.5 in their mitochondria and
      that inhibition of both channels with specific membrane-permeant drugs can
      efficiently induce apoptosis in a macrophage cell line. Thus, our results
      indicate that the mechanism proposed for Kv1.3 can be extended to other Kv
      channels and suggest that membrane-permeant drugs may be a novel pharmacological
      tool for inducing apoptosis in macrophages, important players in the immune
      system. This result could be exploited for the depletion of tumor-associated
      macrophages, which have been shown to foster tumor growth.

PMID- 22856665
TI  - New strategies against prostate cancer--Pt(II)-based chemotherapy.
AB  - Prostate cancer is the second most common cancer worldwide and the sixth cause of
      cancer-related death in men. When hormone therapy fails to control tumour growth,
      castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be
      administered. Since 2004, docetaxel administration is the standard of care in
      metastatic CRPC, although it presents severe limitations such as acquired
      resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA
      in 2010 as a second-line chemotherapeutic agent. Novel immuno- and hormonal
      therapy agents, as well as tumour vaccines, have been recently developed, but new
      strategies are still needed for effectively handling this type of neoplasia.
      Platinum compounds, in particular, have been the object of a growing interest,
      despite the former belief that they should have modest activity against prostate
      cancer. Compounds such as carboplatin, oxaliplatin or satraplatin, either alone
      or in combination, have lately shown promising results. In order to overcome the
      deleterious side-effects usually associated to these metal-based agents, several
      approaches have been followed with a view to optimise drug delivery and
      targeting, some of which showed considerable success in CRPC. Platinum drugs may
      therefore have an important role in the chemotherapeutic management of human
      metastatic castration-resistant prostate cancer, mostly in second-line
      strategies. The present review addresses the most relevant studies on platinum
      based antineoplastic agents towards CRPC in the last decade--from first--and
      second-generation complexes to newly developed compounds.

PMID- 22856666
TI  - Assessment of static telecytological diagnoses' reproducibility in cervical
      smears prepared by means of liquid-based cytology.
AB  - OBJECTIVE: This study evaluated the accuracy and reproducibility of
      telecytological diagnoses proffered on the basis of digitized images from
      cervical smears prepared by means of liquid-based cytology. MATERIALS AND
      METHODS: Representative digital cytological images from a total of 404 cervical
      smears (benign, 135; atypical squamous cells of undetermined significance, 92;
      low-grade squamous intraepithelial lesion, 62; high-grade squamous
      intraepithelial lesion, 87; squamous cell carcinoma, 26; and adenocarcinoma, 2)
      were uploaded to the CytoTrainer e-learning telecytology platform (developed in
      the Department of Cytopathology, "ATTIKON" University General Hospital, Athens,
      Greece) with specific password-protected accounts and were reviewed remotely by
      four independent board-certified cytopathologists (checking round). Their reports
      were recorded and classified. After 12 and 24 months, the same representative
      digital images were transferred in random order to the same cytopathologists and
      were reviewed again (first and second review rounds, respectively). The
      cytopathologists' first and second round diagnoses were recorded and compared
      with their initial ones. RESULTS: Statistical evaluation of cytological diagnoses
      detected no significant difference in diagnostic accuracy among checking and
      review diagnoses. The overall interobserver agreement was almost perfect with
      kappa values of 0.79-0.97, whereas intraobserver agreement ranged from almost
      perfect to perfect with kappa values of 0.76-1 in all diagnostic rounds.
      CONCLUSIONS: Digital images of cervical smears can be used for rapid and accurate
      diagnosis, by diminishing turnaround times and improving small cytology
      departments' quality indices. Diagnoses made by using static telecytological
      systems can be as reliable as those made by using conventional microscopy, under
      the conditions that representative images are taken and that standard cytological
      diagnostic criteria are applied. Telecytology can be used as an alternative
      method for the cytologic diagnosis of cervical smears, particularly in quality
      assurance programs.

PMID- 22856667
TI  - Quantitative evaluation of an automatic segmentation method for 3D reconstruction
      of intervertebral scoliotic disks from MR images.
AB  - BACKGROUND: For some scoliotic patients the spinal instrumentation is inevitable.
      Among these patients, those with stiff curvature will need thoracoscopic disk
      resection. The removal of the intervertebral disk with only thoracoscopic images
      is a tedious and challenging task for the surgeon. With computer aided surgery
      and 3D visualisation of the interverterbral disk during surgery, surgeons will
      have access to additional information such as the remaining disk tissue or the
      distance of surgical tools from critical anatomical structures like the aorta or
      spinal canal. We hypothesized that automatically extracting 3D information of the
      intervertebral disk from MR images would aid the surgeons to evaluate the
      remaining disk and would add a security factor to the patient during
      thoracoscopic disk resection. METHODS: This paper presents a quantitative
      evaluation of an automatic segmentation method for 3D reconstruction of
      intervertebral scoliotic disks from MR images. The automatic segmentation method
      is based on the watershed technique and morphological operators. The 3D Dice
      Similarity Coefficient (DSC) is the main statistical metric used to validate the
      automatically detected preoperative disk volumes. The automatic detections of
      intervertebral disks of real clinical MR images are compared to manual
      segmentation done by clinicians. RESULTS: Results show that depending on the type
      of MR acquisition sequence, the 3D DSC can be as high as 0.79 (+/-0.04). These 3D
      results are also supported by a 2D quantitative evaluation as well as by
      robustness and variability evaluations. The mean discrepancy (in 2D) between the
      manual and automatic segmentations for regions around the spinal canal is of 1.8
      (+/-0.8) mm. The robustness study shows that among the five factors evaluated,
      only the type of MRI acquisition sequence can affect the segmentation results.
      Finally, the variability of the automatic segmentation method is lower than the
      variability associated with manual segmentation performed by different
      physicians. CONCLUSIONS: This comprehensive evaluation of the automatic
      segmentation and 3D reconstruction of intervertebral disks shows that the
      proposed technique used with specific MRI acquisition protocol can detect
      intervertebral disk of scoliotic patient. The newly developed technique is
      promising for clinical context and can eventually help surgeons during
      thoracoscopic intervertebral disk resection.

PMID- 22856668
TI  - Photoelectrocatalytic oxidation of glutathione based on porous TiO2-Pt
      nanowhiskers.
AB  - The performance of TiO(2) nanoparticles is extremely attractive in various areas
      of chemical and biochemical engineering as they can effectively work by combining
      the photocatalytic property with various superior properties of the related
      nanostructure. The relevant photoelectrochemical detection has attracted
      considerable interest and shown potential applications in a wide range of areas.
      In this study, we have prepared new nanowhiskers of platinum-doped titanium
      dioxide (TiO(2)-Pt), which could be further used to fabricate a novel
      nanointerface for the sensitive detection of biomolecules including glutathione
      (GSH). Our observations demonstrate that the sensitive TiO(2)-Pt nanowhiskers
      biointerface could be readily fabricated by casting the TiO(2)-Pt nanowhiskers
      suspension on a glassy carbon electrode (GCE), which could readily combine the
      photocatalytic and eletrocatalytic properties of TiO(2) nanocomposites to
      introduce a novel photoelectrocatalytic biosensor for GSH detection in real
      samples. Compared to other analysis strategies, the TiO(2)-Pt nanowhiskers
      modified GCE showed a considerably high sensitivity for the detection of GSH due
      to the excellent photoelectrocatalytic ability of the porous TiO(2)-Pt
      nanowhiskers. Scanning electron microscopy (SEM), Raman spectroscopy, and
      electrochemical impedance spectroscopy have shown that Pt can readily blend with
      porous TiO(2) nanowhiskers and facilitate the relevant catalysis property of
      TiO(2), resulting in the enhanced photoelectrocatalytic effect. Thus, through the
      new strategy of the utilization of the excellent photoelectrocatalytic property
      of TiO(2)-Pt nanocomposites, it is possible to realize the rapid electrochemical
      detection of glutathione with high sensitivity, low cost, and good
      reproducibility.

PMID- 22856669
TI  - Long-range atmospheric transport of polycyclic aromatic hydrocarbons: a global 3
      D model analysis including evaluation of Arctic sources.
AB  - We use the global 3-D chemical transport model GEOS-Chem to simulate long-range
      atmospheric transport of polycyclic aromatic hydrocarbons (PAHs). To evaluate the
      model's ability to simulate PAHs with different volatilities, we conduct analyses
      for phenanthrene (PHE), pyrene (PYR), and benzo[a]pyrene (BaP). GEOS-Chem
      captures observed seasonal trends with no statistically significant difference
      between simulated and measured mean annual concentrations. GEOS-Chem also
      captures variability in observed concentrations at nonurban sites (r = 0.64,
      0.72, and 0.74, for PHE, PYR, and BaP). Sensitivity simulations suggest snow/ice
      scavenging is important for gas-phase PAHs, and on-particle oxidation and
      temperature-dependency of gas-particle partitioning have greater effects on
      transport than irreversible partitioning or increased particle concentrations.
      GEOS-Chem estimates mean atmospheric lifetimes of <1 day for all three PAHs.
      Though corresponding half-lives are lower than the 2-day screening criterion for
      international policy action, we simulate concentrations at the high-Arctic
      station of Spitsbergen within four times observed concentrations with strong
      correlation (r = 0.70, 0.68, and 0.70 for PHE, PYR, and BaP). European and
      Russian emissions combined account for ~80% of episodic high-concentration events
      at Spitsbergen.

PMID- 22856670
TI  - Chemotherapy-related changes in central nervous system phospholipids and
      neurocognitive function in childhood acute lymphoblastic leukemia.
AB  - Long-term survivors of childhood leukemia are at risk for neurocognitive
      impairment, although the neurophysiological basis is not well understood. The
      purpose of this study was to explore associations between changes in
      cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children
      undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children
      were followed prospectively from diagnosis. CSF samples were collected during
      scheduled lumbar punctures and phospholipids were extracted. Neurocognitive
      evaluations were conducted annually beginning shortly after diagnosis.
      Concentrations of sphingomyelin (SM) increased following induction (p = 0.03) and
      consolidation (p = 0.04), while lysophosphatidylcholine (LPC) increased following
      induction (p = 0.003). Multivariable analyses demonstrated associations between
      post-induction SM and motor speed at 1 year (p < 0.001), 2 years (p = 0.001) and
      3 years (p = 0.02) following diagnosis. Post-induction LPC was associated with
      verbal working memory (p = 0.007). Results indicate that early changes in
      phospholipids are related to neurocognitive decline and suggest a chemotherapy
      impact on white matter integrity.

PMID- 22856671
TI  - Impact of 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase on IVF
      outcome: is screening necessary for all infertile women?
AB  - AIM: Polymorphisms of genes connected to folate metabolism may alter the
      beneficial effect of folic acid on the methyl group cycle. The most common
      variation is the 677C>T polymorphism of the gene of the 5,10
      methylentetrahydrofolate reductase (MTHFR). The aim of this study is to
      investigate of what influence, if any, does MTHFR 677C>T mutation have on female
      fertility and on the in vitro fertilization (IVF) outcome. PATIENTS AND METHODS:
      Data of 273 patients were retrospectively analyzed. The study group (group A)
      consisted of 103 women, homozygous for the MTHFR 677C>T mutant genotype. The
      control group (group B) consisted of 170 patients without the mutation. RESULTS:
      A longer stimulation duration was found in group A and the total amount of
      recombinant follicle-stimulating hormone (r-FSH) needed was appreciably higher.
      The fertilization rate was significantly higher in group B, although the
      implantation rate and clinical pregnancies were similar in both groups.
      CONCLUSIONS: Alteration of inherited thrombophilic factors is connected with
      early pregnancy loss and IVF implantation failure. Our study showed an abortion
      rate higher, but not statistically significant, in group A. Based on these
      findings, our study suggests that MTHFR 677C>T mutation does not affect the IVF
      outcome and patients without thrombophilic risk factors undergoing an IVF cycle
      should not all be screened for thrombophilic disorders.

PMID- 22856672
TI  - PSP/reg: a new stone in sepsis biomarkers?
AB  - Rapid diagnosis, appropriate management, and time are the key factors for
      improving survival rate in many emergency clinical scenarios such as acute
      myocardial infarction, pulmonary embolism, cerebral stroke, and severe sepsis.
      Clinical signs and electrocardiographic, radiological, and echographic
      investigations associated with biomarkers usually allow a quick diagnosis in all
      of the above situations, except severe sepsis, in which the diagnosis in the
      early phases is often only presumptive. In sepsis, microbiological cultures are
      still considered the 'gold standard' for diagnosis, whereas the numerous
      biomarkers investigated are actually valuable only for patient stratification and
      evaluation of clinical course. In this issue of Critical Care, Que and colleagues
      describe the prognostic value of pancreatic stone protein/regenerating protein
      (PSP/reg) concentration in patients with severe infections. The data reported are
      interesting, but several questions about this biomarker arise, and further
      studies are needed to understand its role in sepsis and clinical practice. 

PMID- 22856673
TI  - AGORA: Assembly Guided by Optical Restriction Alignment.
AB  - BACKGROUND: Genome assembly is difficult due to repeated sequences within the
      genome, which create ambiguities and cause the final assembly to be broken up
      into many separate sequences (contigs). Long range linking information, such as
      mate-pairs or mapping data, is necessary to help assembly software resolve
      repeats, thereby leading to a more complete reconstruction of genomes. Prior work
      has used optical maps for validating assemblies and scaffolding contigs, after an
      initial assembly has been produced. However, optical maps have not previously
      been used within the genome assembly process. Here, we use optical map
      information within the popular de Bruijn graph assembly paradigm to eliminate
      paths in the de Bruijn graph which are not consistent with the optical map and
      help determine the correct reconstruction of the genome. RESULTS: We developed a
      new algorithm called AGORA: Assembly Guided by Optical Restriction Alignment.
      AGORA is the first algorithm to use optical map information directly within the
      de Bruijn graph framework to help produce an accurate assembly of a genome that
      is consistent with the optical map information provided. Our simulations on
      bacterial genomes show that AGORA is effective at producing assemblies closely
      matching the reference sequences.Additionally, we show that noise in the optical
      map can have a strong impact on the final assembly quality for some complex
      genomes, and we also measure how various characteristics of the starting de
      Bruijn graph may impact the quality of the final assembly. Lastly, we show that a
      proper choice of restriction enzyme for the optical map may substantially improve
      the quality of the final assembly. CONCLUSIONS: Our work shows that optical maps
      can be used effectively to assemble genomes within the de Bruijn graph assembly
      framework. Our experiments also provide insights into the characteristics of the
      mapping data that most affect the performance of our algorithm, indicating the
      potential benefit of more accurate optical mapping technologies, such as nano
      coding.

PMID- 22856674
TI  - Cumulative keyboard strokes: a possible risk factor for carpal tunnel syndrome.
AB  - ABSTRACT:  BACKGROUND: Contradictory reports have been published regarding the
      association of Carpal Tunnel Syndrome (CTS) and the use of computer keyboard.
      Previous studies did not take into account the cumulative exposure to keyboard
      strokes among computer workers. The aim of the present study was to investigate
      the association between cumulative keyboard use (keyboard strokes) and CTS.
      METHODS: Employees (461) from a Governmental data entry & processing unit agreed
      to participate (response rate: 84.1 %) in a cross-sectional study. Alpha
      questionnaire was distributed to the participants to obtain information on socio
      demographics and risk factors for CTS. The participants were examined for signs
      and symptoms related to CTS and were asked if they had previous history or
      surgery for CTS. The cumulative amount of the keyboard strokes per worker per
      year was calculated by the use of payroll's registry. Two case definitions for
      CTS were used. The first included subjects with personal history/surgery for CTS
      while the second included subjects that belonged to the first case definition
      plus those participants were identified through clinical examination. RESULTS:
      Multivariate analysis used for both case definitions, indicated that those
      employees with high cumulative exposure to keyboard strokes were at increased
      risk of CTS (case definition A: OR = 2.23;95 % CI = 1.09-4.52 and case definition
      B: OR = 2.41; 95%CI = 1.36-4.25). A dose response pattern between cumulative
      exposure to keyboard strokes and CTS has been revealed (p < 0.001). CONCLUSIONS:
      The present study indicated a possible association between cumulative exposure to
      keyboard strokes and development of CTS. Cumulative exposure to key-board strokes
      would be taken into account as an exposure indicator regarding exposure
      assessment of computer workers. Further research is needed in order to test the
      results of the current study and assess causality between cumulative keyboard
      strokes and development of CT.

PMID- 22856675
TI  - Air pollution during pregnancy and neonatal outcome: a review.
AB  - There is increasing evidence of the adverse impact of prenatal exposure to air
      pollution. This is of particular interest, as exposure during pregnancy--a
      crucial time span of important biological development--may have long-term
      implications. The aims of this review are to show current epidemiological
      evidence of known effects of prenatal exposure to air pollution and present
      possible mechanisms behind this process. Harmful effects of exposure to air
      pollution during pregnancy have been shown for different birth outcomes: higher
      infant mortality, lower birth weight, impaired lung development, increased later
      respiratory morbidity, and early alterations in immune development. Although
      results on lower birth weight are somewhat controversial, evidence for higher
      infant mortality is consistent in studies published worldwide. Possible
      mechanisms include direct toxicity of particles due to particle translocation
      across tissue barriers or particle penetration across cellular membranes. The
      induction of specific processes or interaction with immune cells in either the
      pregnant mother or the fetus may be possible consequences. Indirect effects could
      be oxidative stress and inflammation with consequent hemodynamic alterations
      resulting in decreased placental blood flow and reduced transfer of nutrients to
      the fetus. The early developmental phase of pregnancy is thought to be very
      important in determining long-term growth and overall health. So-called
      "tracking" of somatic growth and lung function is believed to have a huge impact
      on long-term morbidity, especially from a public health perspective. This is
      particularly important in areas with high levels of outdoor pollution, where it
      is practically impossible for an individual to avoid exposure. Especially in
      these areas, good evidence for the association between prenatal exposure to air
      pollution and infant mortality exists, clearly indicating the need for more
      stringent measures to reduce exposure to air pollution.

PMID- 22856676
TI  - Spatial visual contrast sensitivity in liver transplanted Portuguese familial
      amyloidotic polyneuropathy (ATTR V30M) patients.
AB  - Liver transplanted patients with familial amyloidosis (FAP) patients develop
      earlier presbyopia due to the deposition of amyloid on the anterior capsule of
      the lens. Despite normal visual acuity of 20/20 Snellen chart, some patients
      reported complaints of impaired vision. The aim of this study is to investigate
      the visual spatial contrast sensitivity in these patients. This is a
      retrospective, nonrandomized study. Spatial contrast sensitivity was performed in
      both eyes of 25 FAP patients with best correct visual acuity of 20/20 Snellen
      chart. In each patient, one eye had visible opacification of anterior capsule of
      the lens. FAP patients had poorer visual contrast sensitivity than normal even in
      absence of visible opacification of the anterior capsule of the lens. Comparing
      eyes with visible opacification of anterior capsule of the lens with eyes without
      visible opacification of the anterior capsule of the lens, a worse visual
      sensitivity was observed at all frequencies tested. This occurred with similar
      lacrimal function in both groups. The eyes of FAP patients have decreased spatial
      contrast sensitivity which is worse in presence of visible opacification of the
      anterior capsule of the lens. This could explain the visual complaints in
      presence of normal visual acuity by Snellen chart.

PMID- 22856677
TI  - Copolymer coatings consisting of 2-methacryloyloxyethyl phosphorylcholine and 3
      methacryloxypropyl trimethoxysilane via ATRP to improve cellulose
      biocompatibility.
AB  - AB diblock copolymers comprised of poly(2-methacryloyloxyethyl phosphorylcholine)
      (PMPC) and poly(3-methacryloxypropyl trimethoxysilane) (PMTSi) segments, which
      are used for biocompatible coatings, were investigated. Block copolymers with
      various compositions were synthesized by atomic transfer radical polymerization
      (ATRP). The obtained copolymers were dissolved in an ethanol solution, and
      dynamic light scattering showed that all block copolymers were capable of
      existing as micelles. After a convenient "one-step" reaction, the cellulose
      membranes could be covalently modified by these copolymers with stable chemical
      bonds (C-O-Si and Si-O-Si). Block copolymers with different PMPC chain length
      were applied to surface modification to find the most suitable copolymer. The
      functional MPC density can be controlled by adjusting the ratio of the two
      monomers (MPC and MTSi), which also affect surface properties, including the
      surface contact angle, surface morphology, and number of functional PC groups.
      The low-fouling properties were measured by protein adsorption, platelet adhesion
      and activation, and cell adhesion. Protein adsorption of bovine serum albumin
      (BSA), fibrinogen, and human plasma were also tested and a moderate monomer
      composite was attained. The protein adsorption behavior on the novel interfaces
      depends both on MPC density and PMPC chain length. Platelet adhesion and
      activation were reduced on all the modified surfaces. The adhesion of Human
      Embryonic Kidney 293 (293T) cells on the coated surfaces also decreased.

PMID- 22856678
TI  - Effect of delaying toothbrushing during bleaching on enamel surface roughness: an
      in vitro study.
AB  - This study aimed to evaluate the effect of toothbrushing on enamel surface
      roughness at three different intervals after daily bleaching treatment. Eighty
      enamel slabs were initially evaluated for surface roughness and then randomly
      divided into four groups. The bleaching procedure was carried out for 21 days,
      six hours daily. In the control group (group 1), the specimens were not brushed
      after bleaching, but in groups 2-4, they were brushed with toothpaste
      immediately, one hour, or two hours after bleaching, respectively. Then the
      specimens were stored in artificial saliva. Enamel surface roughness was
      reevaluated at the end of the period. Kruskal-Wallis and Mann-Whitney U tests
      showed statistically significant differences in the means of surface roughness
      values between the immediately brushed group and the three other groups
      (p<0.001). Daily toothbrushing immediately after bleaching increased enamel
      surface roughness; however, postponing the procedure for one or two hours after
      daily bleaching and exposing the specimens to artificial saliva during the study
      period resulted in enamel surface roughness comparable to that of the control
      group.

PMID- 22856679
TI  - Wear rates of resin composites.
AB  - SUMMARY A laboratory study was conducted to examine the wear of resin composite
      materials using a generalized wear simulation model. Ten specimens each of five
      resin composites (Esthet*X [EX], Filtek Supreme Plus [SP], Filtek Z250 [Z2],
      Tetric EvoCeram [EC], and Z100 Restorative [Z1]) were subjected to wear
      challenges of 100,000, 400,000, 800,000, and 1,200,000 cycles. The materials were
      placed in cylinder-shaped stainless-steel fixtures, and wear was generated using
      a flat stainless-steel antagonist in a slurry of polymethylmethacrylate beads.
      Wear (mean facet depth [MUm] and volume loss [mm(3)]) was determined using a
      noncontact profilometer (Proscan 2000) with Proscan and ProForm software.
      Statistical analysis of the laboratory data using analysis of variance and
      Tukey's post hoc test showed a significant difference (p<0.05) for mean wear
      facet depth and volume loss for both the number of cycles and resin composite
      material. Linear regression analysis was used to develop predictive wear rates
      and volume loss rates. Linear wear was demonstrated with correlation coefficients
      (R(2)) ranging from 0.914 to 0.995. Mean wear values (mean facet depth [MUm]) and
      standard deviations (SD) for 1200K cycles were as follows: Z1 13.9 (2.0), Z2 26.7
      (2.7), SP 30.1 (4.1), EC 31.8 (2.3), and EX 67.5 (8.2). Volume loss (mm(3)) and
      SDs for 1200K cycles were as follows: Z1 0.248 (0.036), Z2 0.477 (0.044), SP
      0.541 (0.072), EC 0.584 (0.037), and EX 1.162 (0.139). The wear rate (MUm) and
      volume loss rate (mm(3)) per 100,000 cycles for the five resin composites were as
      follows: wear rate Z1 0.58, EC 1.27, Z2 1.49, SP 1.62, and EX 4.35, and volume
      loss rate Z1 0.009, EC 0.024, Z2 0.028, SP 0.029, and EX 0.075. The generalized
      wear model appears to be an excellent method for measuring relative wear of resin
      composite materials.

PMID- 22856680
TI  - Clinical evaluation of ceramic inlays and onlays fabricated with two systems:
      five-year follow-up.
AB  - This study evaluated the five-year clinical performance of ceramic inlays and
      onlays made with two systems: sintered Duceram (Dentsply-Degussa) and pressable
      IPS Empress (Ivoclar Vivadent). Eighty-six restorations were placed by a single
      operator in 35 patients with a median age of 33 years. The restorations were
      cemented with dual-cured resin cement (Variolink II, Ivoclar Vivadent) and Syntac
      Classic adhesive under rubber dam. The evaluations were conducted by two
      independent investigators at baseline, and at one, two, three, and five years
      using the modified United States Public Health Service (USPHS) criteria. At the
      five-year recall, 26 patients were evaluated (74.28%), totalling 62 (72.09%)
      restorations. Four IPS restorations were fractured, two restorations presented
      secondary caries (one from IPS and one from Duceram), and two restorations showed
      unacceptable defects at the restoration margin and needed replacement (one
      restoration from each ceramic system). A general success rate of 87% was
      recorded. The Fisher exact test revealed no significant difference between
      Duceram and IPS Empress ceramic systems for all aspects evaluated at different
      recall appointments (p>0.05). The McNemar chi-square test showed significant
      differences in relation to marginal discoloration, marginal integrity, and
      surface texture between the baseline and five-year recall for both systems
      (p<0.001), with an increased percentage of Bravo scores. However, few Charlie or
      Delta scores were attributed to these restorations. In conclusion, these two
      types of ceramic materials demonstrated acceptable clinical performance after
      five years.

PMID- 22856681
TI  - Noncarious cervical lesions restored with three different tooth-colored
      materials: two-year results.
AB  - INTRODUCTION: The aim of this two-year prospective clinical study was to evaluate
      and compare the clinical performance of three different adhesive esthetic
      materials in noncarious cervical lesions. MATERIAL AND METHODS: A total of 90
      restorations (30 per material) were placed in 30 patients who ranged in age
      between 18 and 50 years and of both genders, by a single operator with no
      previous preparation. The restoration of noncarious cervical lesions was done
      with either a microfilled composite (Esthet.X/Dentsply/De Trey, Konstanz,
      Germany, and Prime&Bond NT/Dentsply/De Trey), a nanohybrid composite
      (TetricEvoCeram/Vivadent, Schaan, Liechtenstein, and AdheSE/Vivadent), or a
      compomer (Dyract eXtra/Dentsply/De Trey and Xeno III Dentsply/De Trey). All
      restorations were evaluated by independent examiners using a modified US Public
      Health Service criteria at baseline and after 12 and 24 months for six clinical
      categories. Data were analyzed statistically by Pearson's chi-square or the
      Fisher's exact test at 5% significance level (p<0.05). RESULTS: Results showed
      that most of the restorations were clinically satisfactory after 12 and 24
      months, with no statistically significant differences among the three groups for
      all evaluated criteria. CONCLUSION: Treatment of noncarious cervical lesions
      using composite and compomer materials, combined with the appropriate adhesive
      systems and properly implemented restorative procedures, gives satisfactory
      results after a two-year evaluation period.

PMID- 22856682
TI  - Effects of surface treatments, thermocycling, and cyclic loading on the bond
      strength of a resin cement bonded to a lithium disilicate glass ceramic.
AB  - SUMMARY Objectives : The aim of this present study was to investigate the effect
      of two surface treatments, fatigue and thermocycling, on the microtensile bond
      strength of a newly introduced lithium disilicate glass ceramic (IPS e.max Press,
      Ivoclar Vivadent) and a dual-cured resin cement. Methods : A total of 18 ceramic
      blocks (10 mm long * 7 mm wide * 3.0 mm thick) were fabricated and divided into
      six groups (n=3): groups 1, 2, and 3-air particle abraded for five seconds with
      50-MUm aluminum oxide particles; groups 4, 5, and 6-acid etched with 10%
      hydrofluoric acid for 20 seconds. A silane coupling agent was applied onto all
      specimens and allowed to dry for five seconds, and the ceramic blocks were bonded
      to a block of composite Tetric N-Ceram (Ivoclar Vivadent) with RelyX ARC (3M
      ESPE) resin cement and placed under a 500-g static load for two minutes. The
      cement excess was removed with a disposable microbrush, and four periods of light
      activation for 40 seconds each were performed at right angles using an LED curing
      unit (UltraLume LED 5, Ultradent) with a final 40 second light exposure from the
      top surface. All of the specimens were stored in distilled water at 37 degrees C
      for 24 hours. Groups 2 and 5 were submitted to 3,000 thermal cycles between 5
      degrees C and 55 degrees C, and groups 3 and 6 were submitted to a fatigue test
      of 100,000 cycles at 2 Hz. Specimens were sectioned perpendicular to the bonding
      area to obtain beams with a cross-sectional area of 1 mm(2) (30 beams per group)
      and submitted to a microtensile bond strength test in a testing machine (EZ Test)
      at a crosshead speed of 0.5 mm/min. Data were submitted to analysis of variance
      and Tukey post hoc test (p<=0.05). Results : The microtensile bond strength
      values (MPa) were 26.9 +/- 6.9, 22.2 +/- 7.8, and 21.2 +/- 9.1 for groups 1-3 and
      35.0 +/- 9.6, 24.3 +/- 8.9, and 23.9 +/- 6.3 for groups 4-6. For the control
      group, fatigue testing and thermocycling produced a predominance of adhesive
      failures. Fatigue and thermocycling significantly decreased the microtensile bond
      strength for both ceramic surface treatments when compared with the control
      groups. Etching with 10% hydrofluoric acid significantly increased the
      microtensile bond strength for the control group.

PMID- 22856683
TI  - Melatonin-rich transgenic rice plants exhibit resistance to herbicide-induced
      oxidative stress.
AB  - To examine whether melatonin-rich plants can defend against oxidative stress, we
      subjected melatonin-rich transgenic (MRT) rice plants to the singlet-oxygen
      generating herbicide butafenacil. Both MRT and transgenic control (TC; expressing
      the vector only) rice seeds germinated and grew equally well in continuous dark
      on half-strength Murashige and Skoog (MS) medium containing 0.1 MUm butafenacil.
      However, after transferring the seedlings to light, the TCs rapidly necrotized,
      whereas the MRT seedlings showed resistant phenotypes. Seven-day-old MRT
      seedlings treated with 0.1 MUm butafenacil were resistant to the herbicide and
      contained high chlorophyll levels and low malondialdehyde and hydrogen peroxide
      contents compared with the TCs. As they did before the herbicide treatment, the
      MRT plants also produced much more melatonin after the herbicide treatment than
      the TCs. In addition, the MRT plants exhibited higher superoxide dismutase and
      catalase activities before and after the herbicide treatment compared with the
      TCs. This is the first report showing that MRT plants exhibit resistance against
      a peroxidizing herbicide that acts by generating reactive oxygen species (ROS)
      that kill plants. This result indicates that melatonin scavenges ROS efficiently
      in vivo in the transgenic plants, leading to oxidative stress resistance.

PMID- 22856684
TI  - Gene expression profiles in white blood cells of volunteers exposed to a 50 Hz
      electromagnetic field.
AB  - Consistent and independently replicated laboratory evidence to support a
      causative relationship between environmental exposure to extremely low-frequency
      electromagnetic fields (EMFs) at power line frequencies and the associated
      increase in risk of childhood leukemia has not been obtained. In particular,
      although gene expression responses have been reported in a wide variety of cells,
      none has emerged as robust, widely replicated effects. DNA microarrays facilitate
      comprehensive searches for changes in gene expression without a requirement to
      select candidate responsive genes. To determine if gene expression changes occur
      in white blood cells of volunteers exposed to an ELF-EMF, each of 17 pairs of
      male volunteers age 20-30 was subjected either to a 50 Hz EMF exposure of 62.0 +/
      7.1 MUT for 2 h or to a sham exposure (0.21 +/- 0.05 MUT) at the same time
      (11:00 a.m. to 13:00 p.m.). The alternative regime for each volunteer was
      repeated on the following day and the two-day sequence was repeated 6 days later,
      with the exception that a null exposure (0.085 +/- 0.01 MUT) replaced the sham
      exposure. Five blood samples (10 ml) were collected at 2 h intervals from 9:00 to
      17:00 with five additional samples during the exposure and sham or null exposure
      periods on each study day. RNA samples were pooled for the same time on each
      study day for the group of 17 volunteers that were subjected to the ELF-EMF
      exposure/sham or null exposure sequence and were analyzed on Illumina
      microarrays. Time courses for 16 mammalian genes previously reported to be
      responsive to ELF-EMF exposure, including immediate early genes, stress response,
      cell proliferation and apoptotic genes were examined in detail. No genes or gene
      sets showed consistent response profiles to repeated ELF-EMF exposures. A stress
      response was detected as a transient increase in plasma cortisol at the onset of
      either exposure or sham exposure on the first study day. The cortisol response
      diminished progressively on subsequent exposures or sham exposures, and was
      attributable to mild stress associated with the experimental protocol.

PMID- 22856685
TI  - Calcium-dependent interaction of calmodulin with human 80S ribosomes and
      polyribosomes.
AB  - Ribosomes are the protein factories of every living cell. The process of protein
      translation is highly complex and tightly regulated by a large number of diverse
      RNAs and proteins. Earlier studies indicate that Ca(2+) plays a role in protein
      translation. Calmodulin (CaM), a ubiquitous Ca(2+)-binding protein, regulates a
      large number of proteins participating in many signaling pathways. Several 40S
      and 60S ribosomal proteins have been identified to interact with CaM, and here,
      we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in
      a Ca(2+)-dependent manner. No binding is observed in buffer with 6 mM Mg(2+) and
      1 mM EGTA that chelates Ca(2+), suggesting high specificity of the CaM-ribosome
      interaction dependent on the Ca(2+) induced conformational change of CaM. The
      interactions between CaM and ribosomes are inhibited by synthetic peptides
      comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a
      cell-free in vitro translation system, we further found that these synthetic
      peptides are potent inhibitors of protein synthesis. Our results identify an
      involvement of CaM in the translational activity of ribosomes.

PMID- 22856686
TI  - Health and nutritional status of children in Ethiopia: do maternal
      characteristics matter?
AB  - In Ethiopia, despite some recent improvements, the health and nutritional status
      of children is very poor. A better understanding of the main socioeconomic
      determinants of child health and nutrition is essential to address the problem
      and make appropriate interventions. In the present study, an attempt is made to
      explore the effect of maternal characteristics on the health and nutritional
      status of under-five children using the 2005 Ethiopian Demographic and Health
      Survey. The health and nutritional status of children are measured using the two
      widely used anthropometric indicators height-for-age (HAZ) and weight-for-height
      (WHZ). In the ordinary least squares (OLS) estimation, it is observed that
      maternal characteristics have a significant impact on child health and
      nutritional status. The magnitudes of the coefficients, however, are found to
      slightly increase when maternal education is instrumented in the 2SLS estimation.
      Moreover, in the quantile regression (QR) estimation, the impacts of maternal
      characteristics are observed to vary between long-term and current child health
      and nutritional status.

PMID- 22856687
TI  - Clinical issues in oesophageal adenocarcinoma: could DNA copy number hold the
      key?
AB  - While not being considered a common cancer, since 1975 oesophageal adenocarcinoma
      (OAC) has had the fastest-rising incidence of any malignancy in Caucasian Western
      populations. In the absence of major improvements in treatment since this rise
      began, the number of deaths has also increased rapidly. In contrast, there have
      been significant advances in basic science in this period. One such advance is
      the discovery of DNA copy number aberrations (CNAs), and their potential role in
      carcinogenesis. The study of CNAs offers the potential to answer fundamental
      clinical questions in OAC, which in turn may lead to improved diagnosis, staging
      and treatment. This review outlines current clinical dilemmas in OAC, discusses
      the role that CNAs have been shown to play to date and highlights potential
      future applications.

PMID- 22856688
TI  - Applying what works: a systematic search of the transfer and implementation of
      promising Indigenous Australian health services and programs.
AB  - BACKGROUND: The transfer and implementation of acceptable and effective health
      services, programs and innovations across settings provides an important and
      potentially cost-effective strategy for reducing Indigenous Australians' high
      burden of disease. This study reports a systematic review of Indigenous health
      services, programs and innovations to examine the extent to which studies
      considered processes of transfer and implementation within and across Indigenous
      communities and healthcare settings. METHODS: Medline, Informit, Infotrac,
      Blackwells Publishing, Proquest, Taylor and Francis, JStor, and the Indigenous
      HealthInfoNet were searched using terms: Aborigin* OR Indigen* OR Torres AND
      health AND service OR program* OR intervention AND Australia to locate
      publications from 1992-2011. The reference lists of 19 reviews were also checked.
      Data from peer reviewed journals, reports, and websites were included. The 95%
      confidence intervals (95% CI) for proportions that referred to and focussed on
      transfer were calculated as exact binomial confidence intervals. Test comparisons
      between proportions were calculated using Fisher's exact test with an alpha level
      of 5%. RESULTS: Of 1311 publications identified, 119 (9.1%; 95% CI: 7.6%-10.8%)
      referred to the transfer and implementation of Indigenous Australian health
      services or programs, but only 21 studies (1.6%; 95% CI: 1.0%-2.4%) actually
      focused on transfer and implementation. Of the 119 transfer studies, 37 (31.1%;
      95% CI: 22.9-40.2%) evaluated the impact of a service or program, 28 (23.5%; 95%
      CI: 16.2%-32.2%) reported only process measures and 54 were descriptive. Of the
      37 impact evaluation studies, 28 (75.7%; 95% CI: 58.8%-88.2%) appeared in peer
      reviewed journals but none included experimental designs. CONCLUSION: While
      services and programs are being transferred and implemented, few studies focus on
      the process by which this occurred or the effectiveness of the service or program
      in the new setting. Findings highlight a need for partnerships between
      researchers and health services to evaluate the transfer and implementation of
      Indigenous health services and programs using rigorous designs, and publish such
      efforts in peer-reviewed journals as a quality assurance mechanism.

PMID- 22856867
TI  - New insights into the mechanism and an expanded scope of the Fe(III)-mediated
      vinblastine coupling reaction.
AB  - A definition of the scope of aromatic substrates that participate with
      catharanthine in an Fe(III)-mediated coupling reaction, an examination of the key
      structural features of catharanthine required for participation in the reaction,
      and the development of a generalized indole functionalization reaction that bears
      little structural relationship to catharanthine itself are detailed. In addition
      to providing insights into the mechanism of the Fe(III)-mediated coupling
      reaction of catharanthine with vindoline suggesting the reaction conducted in
      acidic aqueous buffer may be radical mediated, the studies provide new
      opportunities for the preparation of previously inaccessible vinblastine analogs
      and define powerful new methodology for the synthesis of indole-containing
      natural and unnatural products.

PMID- 22856869
TI  - Patient early session experience and treatment outcome.
AB  - Patient Session Evaluation Questionnaire (SEQ: Stiles, 1980) ratings from early
      in treatment were examined in relation to outcomes during psychodynamic
      psychotherapy. Twenty-eight therapists treated 73 patients at a university-based
      clinic. A relationship between Smoothness ratings and symptom improvement
      approached statistical significance using bivariate correlations and multilevel
      analyses. A significant relationship was found between Positivity ratings and a
      broad scale of patient-rated functional improvement across many domains (i.e.,
      psychopathology, interpersonal, occupational, and social) before and after
      accounting for therapist effects.

PMID- 22856870
TI  - Loss of BCL7A expression correlates with poor disease prognosis in patients with
      early-stage cutaneous T-cell lymphoma.

PMID- 22856868
TI  - Bone-induced streak artifact suppression in sparse-view CT image reconstruction.
AB  - BACKGROUND: In sparse-view CT imaging, strong streak artifacts may appear around
      bony structures and they often compromise the image readability. Compressed
      sensing (CS) or total variation (TV) minimization-based image reconstruction
      method has reduced the streak artifacts to a great extent, but, sparse-view CT
      imaging still suffers from residual streak artifacts. We introduce a new bone
      induced streak artifact reduction method in the CS-based image reconstruction.
      METHODS: We firstly identify the high-intensity bony regions from the image
      reconstructed by the filtered backprojection (FBP) method, and we calculate the
      sinogram stemming from the bony regions only. Then, we subtract the calculated
      sinogram, which stands for the bony regions, from the measured sinogram before
      performing the CS-based image reconstruction. The image reconstructed from the
      subtracted sinogram will stand for the soft tissues with little streak artifacts
      on it. To restore the original image intensity in the bony regions, we add the
      bony region image, which has been identified from the FBP image, to the soft
      tissue image to form a combined image. Then, we perform the CS-based image
      reconstruction again on the measured sinogram using the combined image as the
      initial condition of the iteration. For experimental validation of the proposed
      method, we take images of a contrast phantom and a rat using a micro-CT and we
      evaluate the reconstructed images based on two figures of merit, relative mean
      square error and total variation caused by the streak artifacts. RESULTS: The
      images reconstructed by the proposed method have been found to have smaller
      streak artifacts than the ones reconstructed by the original CS-based method when
      visually inspected. The quantitative image evaluation studies have also shown
      that the proposed method outperforms the conventional CS-based method.
      CONCLUSIONS: The proposed method can effectively suppress streak artifacts
      stemming from bony structures in sparse-view CT imaging.

PMID- 22856871
TI  - Influence of brain-derived neurotrophic factor genetic polymorphisms on the ages
      of onset for heroin dependence in a Chinese population.
AB  - AIM: The study aims at evaluating the association between brain-derived
      neurotrophic factor (BDNF) gene polymorphisms and heroin-dependent patients in
      the Chinese population. Three polymorphisms of the BDNF-gene (rs10835210,
      rs16917234, and rs6265) in 486 heroin-dependent patients and in 226 healthy
      controls were genotyped for analyzing the association of these polymorphisms with
      age of onset of heroin dependence. We defined the healthy cases as "unknown
      phenotype" and used the endophenotype (behavior traits) to stratify the heroin
      dependents group on the basis of self-reporting traits for examining the
      association between BDNF polymorphisms (rs10835210, rs16917234, and rs6265) and
      heroin dependence. RESULTS: Allelic distributions of BDNF gene polymorphisms did
      not differ significantly between heroin-dependent patients and controls. However,
      we found that the AA carriers of BDNF rs6265 had an earlier onset of heroin
      dependence and a clearer tendency of family history of heroin-dependent than GG
      carriers after controlling behavior characteristics across rs6265 genotypes.
      CONCLUSIONS: Our findings suggested that the BDNF genetic polymorphism (rs6265)
      may have effects on the age of onset of heroin dependence among the Chinese
      population. The BDNF gene could contribute to vulnerabilities to heroin
      dependence.

PMID- 22856872
TI  - The complete mitochondrial genome of Leucoptera malifoliella Costa (Lepidoptera:
      Lyonetiidae).
AB  - The mitochondrial genome (mitogenome) of Leucoptera malifoliella (=L. scitella)
      (Lepidoptera: Lyonetiidae) was sequenced. The size was 15,646 bp with gene
      content and order the same as those of other lepidopterans. The nucleotide
      composition of L. malifoliella mitogenome is highly A+T biased (82.57%), ranked
      just below Coreana raphaelis (82.66%) (Lepidoptera: Lycaenidae). All protein
      coding genes (PCGs) start with the typical ATN codon except for the cox1 gene,
      which uses CGA as the initiation codon. Nine PCGs have the common stop codon TAA,
      four PCGs have the common stop codon T as incomplete stop codons, and nad4l and
      nad6 have TAG as the stop codon. Cloverleaf secondary structures were inferred
      for 22 tRNA genes, but trnS1(AGN) was found to lack the DHU stem. The secondary
      structure of rrnL and rrnS is generally similar to other lepidopterans but with
      some minor differences. The A+T-rich region includes the motif ATAGA, but the
      poly (T) stretch is replaced by a stem-loop structure, which may have a similar
      function to the poly (T) stretch. Finally, there are three long repeat (154 bp)
      sequences followed by one short repeat (56 bp) with four (TA)(n) intervals, and a
      10-bp poly-A is present upstream of trnM. Phylogenetic analysis shows that the
      position of Yponomeutoidea, as represented by L. malifoliella, is the same as
      traditional classifications. Yponomeutoidea is the sister to the other
      lepidopteran superfamilies covered in the present study.

PMID- 22856874
TI  - Editorial: oncolytic viruses.

PMID- 22856873
TI  - Evaluation of common genetic variants in 82 candidate genes as risk factors for
      neural tube defects.
AB  - BACKGROUND: Neural tube defects (NTDs) are common birth defects (~1 in 1000
      pregnancies in the US and Europe) that have complex origins, including
      environmental and genetic factors. A low level of maternal folate is one well
      established risk factor, with maternal periconceptional folic acid
      supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene
      variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and
      MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized
      that variants in additional folate/B12 pathway genes contribute to NTD risk.
      METHODS: A tagSNP approach was used to screen common variation in 82 candidate
      genes selected from the folate/B12 pathway and NTD mouse models. We initially
      genotyped polymorphisms in 320 Irish triads (NTD cases and their parents),
      including 301 cases and 341 Irish controls to perform case-control and family
      based association tests. Significantly associated polymorphisms were genotyped in
      a secondary set of 250 families that included 229 cases and 658 controls. The
      combined results for 1441 SNPs were used in a joint analysis to test for case and
      maternal effects. RESULTS: Nearly 70 SNPs in 30 genes were found to be associated
      with NTDs at the p < 0.01 level. The ten strongest association signals (p-value
      range: 0.0003-0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN,
      GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor
      MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new
      candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor
      allele). Though nominally significant, these associations did not remain
      significant after correction for multiple hypothesis testing. CONCLUSIONS: To our
      knowledge, with respect to sample size and scope of evaluation of candidate
      polymorphisms, this is the largest NTD genetic association study reported to
      date. The scale of the study and the stringency of correction are likely to have
      contributed to real associations failing to survive correction. We have produced
      a ranked list of variants with the strongest association signals. Variants in the
      highest rank of associations are likely to include true associations and should
      be high priority candidates for further study of NTD risk.

PMID- 22856875
TI  - Virus-poly(3,4-ethylenedioxythiophene) biocomposite films.
AB  - Virus-poly(3,4-ethylenedioxythiophene) (virus-PEDOT) biocomposite films are
      prepared by electropolymerizing 3,4-ethylenedioxythiophene (EDOT) in aqueous
      electrolytes containing 12 mM LiClO(4) and the bacteriophage M13. The
      concentration of virus in these solutions, [virus](soln), is varied from 3 to 15
      nM. A quartz crystal microbalance is used to directly measure the total mass of
      the biocomposite film during its electrodeposition. In combination with a
      measurement of the electrodeposition charge, the mass of the virus incorporated
      into the film is calculated. These data show that the concentration of the M13
      within the electropolymerized film, [virus](film), increases linearly with
      [virus](soln). The incorporation of virus particles into the PEDOT film from
      solution is efficient, resulting in a concentration ratio of
      [virus](film):[virus](soln) ~ 450. Virus incorporation into the PEDOT causes
      roughening of the film topography that is observed using scanning electron
      microscopy and atomic force microscopy (AFM). The electrical conductivity of the
      virus-PEDOT film, measured perpendicular to the plane of the film using
      conductive tip AFM, decreases linearly with virus loading, from 270 MUS/cm for
      pure PEDOT films to 50 MUS/cm for films containing 100 MUM virus. The presence on
      the virus surface of displayed affinity peptides did not significantly influence
      the efficiency of incorporation into virus-PEDOT biocomposite films.

PMID- 22856876
TI  - Pulmonary vaccine delivery: a realistic approach?
AB  - Pulmonary vaccine delivery has gained increasing attention during the last decade
      because this vaccination method combines potential advantages such as the fact
      that it omits the use of needles and may elicit immunity at the port of entry for
      many pathogens. In this review the current status of pulmonary vaccination, the
      potential advantages of pulmonary vaccine delivery, the hurdles to overcome in
      the future, and the overall perspectives of this vaccination strategy are
      described.

PMID- 22856877
TI  - Medicinal ethnobotany in Huacareta (Chuquisaca, Bolivia).
AB  - BACKGROUND: The aim of this study was to document the types of diseases treated
      by the use of medicinal plants, their main applications and also to have a report
      of the major diseases treated at the Hospital of San Pablo de Huacareta
      (Chuquisaca Bolivia). METHODS: We conducted semi-structured interviews on the use
      medicinal plants with 10 local informants, and categorized the kinds of diseases
      treated by traditional medicine. We obtained reports of cases treated at the
      Hospital of Huacareta in order to compare the use frequency of traditional
      medicine and allopathic medicine for the treatment of recurrent diseases in the
      area. RESULTS: Our survey identified 258 traditional medicine uses, spanning a
      total of 13 diseases categories and including 91 native and exotic plant species
      and one unidentified sample plant type. Gastrointestinal disorders (55%) were
      most frequently treated with medicinal plants, followed by afflictions of the
      musculoskeletal system (25%) and dermatological disorders (24%). Hospital
      information indicates that the most common diseases are acute respiratory
      infections (47%) and acute diarrheal diseases (37%). The herbal remedies were
      mostly used in the form of teas and decoctions. The informants used mainly native
      plant species, although exotic species has been introduced to the pharmacopoeia.
      CONCLUSIONS: The treatment of gastrointestinal disorders is the primary objective
      of the medical ethnobotany of the inhabitants of Huacareta, while respiratory
      system diseases are mostly treated in the hospital. Looking at the data from the
      Hospital records we can infer that gastrointestinal disorders are among the most
      common diseases in the study area. For most respondents, traditional medicine is
      a reliable choice for the care of their illnesses. However, the preference of the
      population for either traditional medicine or allopathic medicine needs to be
      clarified in future comparative studies to obtain more convincing results. The
      results presented can be used as a base for subsequent work related to
      traditional medicine and its contribution to allopathic medicine in San Pablo de
      Huacareta.

PMID- 22856878
TI  - Copper(0) nanoparticles supported on silica-coated cobalt ferrite magnetic
      particles: cost effective catalyst in the hydrolysis of ammonia-borane with an
      exceptional reusability performance.
AB  - Herein we report the development of a new and cost-effective nanocomposite
      catalyst for the hydrolysis of ammonia-borane (NH(3)BH(3)), which is considered
      to be one of the most promising solid hydrogen carriers because of its high
      gravimetric hydrogen storage capacity (19.6% wt) and low molecular weight. The
      new catalyst system consisting of copper nanoparticles supported on magnetic
      SiO(2)/CoFe(2)O(4) particles was reproducibly prepared by wet-impregnation of
      Cu(II) ions on SiO(2)/CoFe(2)O(4) followed by in situ reduction of the Cu(II)
      ions on the surface of magnetic support during the hydrolysis of NH(3)BH(3) and
      characterized by ICP-MS, XRD, XPS, TEM, HR-TEM and N(2) adsorption-desorption
      technique. Copper nanoparticles supported on silica coated cobalt(II) ferrite
      SiO(2)/CoFe(2)O(4) (CuNPs@SCF) act as highly active catalyst in the hydrolysis of
      ammonia-borane, providing an initial turnover frequency of TOF = 2400 h(-1) at
      room temperature, which is not only higher than all the non-noble metal catalysts
      but also higher than the majority of the noble metal based homogeneous and
      heterogeneous catalysts employed in the same reaction. More importantly, they
      were easily recovered by using a permanent magnet in the reactor wall and reused
      for up to 10 recycles without losing their inherent catalytic activity
      significantly, which demonstrates the exceptional reusability of the CuNPs@SCF
      catalyst.

PMID- 22856879
TI  - A web-based multi-genome synteny viewer for customized data.
AB  - BACKGROUND: Web-based synteny visualization tools are important for sharing data
      and revealing patterns of complicated genome conservation and rearrangements.
      Such tools should allow biologists to upload genomic data for their own analysis.
      This requirement is critical because individual biologists are generating large
      amounts of genomic sequences that quickly overwhelm any centralized web resources
      to collect and display all those data. Recently, we published a web-based synteny
      viewer, GSV, which was designed to satisfy the above requirement. However, GSV
      can only compare two genomes at a given time. Extending the functionality of GSV
      to visualize multiple genomes is important to meet the increasing demand of the
      research community. RESULTS: We have developed a multi-Genome Synteny Viewer
      (mGSV). Similar to GSV, mGSV is a web-based tool that allows users to upload
      their own genomic data files for visualization. Multiple genomes can be presented
      in a single integrated view with an enhanced user interface. Users can navigate
      through all the selected genomes in either pairwise or multiple viewing mode to
      examine conserved genomic regions as well as the accompanying genome annotations.
      Besides serving users who manually interact with the web server, mGSV also
      provides Web Services for machine-to-machine communication to accept data sent by
      other remote resources. The entire mGSV package can also be downloaded for easy
      local installation. CONCLUSIONS: mGSV significantly enhances the original
      functionalities of GSV. A web server hosting mGSV is provided at http://cas
      bioinfo.cas.unt.edu/mgsv.

PMID- 22856880
TI  - Hypouricemic effect of the methanol extract from Prunus mume fruit in mice.
AB  - CONTEXT: The fruit of the Prunus mume Sieb. et Zucc (Rosaceae) is used as a
      health food or medicinal material in traditional herb medicine for a long time in
      Eastern Asian countries. OBJECTIVE: Our present study investigated the
      hypouricemic effect of the methanol extract from P. mume fruit (MPMF) in mice
      with potassium oxonate-induced hyperuremia. MATERIALS AND METHODS: Effect of MPMF
      (35, 70 and 140 mg/kg, p.o.) administrated for 7 days on the serum, liver,
      urinary uric acid levels and liver xanthine oxidase (XO) activity were assessed
      in mice. RESULTS: Hyperuricemic mice induced by potassium oxonate demonstrated an
      elevation in serum and liver uric acid levels (11.0 mg/dL and 0.52 mg/g tissue)
      and a reduction in urinary uric acid levels (49.9 mg/dL). Oral administration of
      140 mg/kg MPMF for 7 days reversed the abnormalities in serum, liver and urinary
      uric acid levels (7.1 mg/dL, 0.37 mg/g tissue and 69.7 mg/dL, respectively). In
      addition, 70 and 140 mg/kg MPMF (3.1 and 2.9 nmol/min per mg protein) inhibited
      liver XO activity compared with hyperuricemic mice (3.9 nmol/min per mg protein).
      DISCUSSION AND CONCLUSION: The results indicated that the beneficial
      hypouricaemic effect of MPMF may be mediated, at least in part, by inhibiting XO
      activity in the liver. Our study suggests that P. mume and its extracts may have
      a considerable potential for development as an anti-gout agent for clinical
      application.

PMID- 22856881
TI  - Religious affiliation and under-five mortality in Mozambique.
AB  - The influence of religion on health remains a subject of considerable debate both
      in developed and developing settings. This study examines the connection between
      the religious affiliation of the mother and under-five mortality in Mozambique.
      It uses unique retrospective survey data collected in a predominantly Christian
      area in Mozambique to compare under-five mortality between children of women
      affiliated to organized religion and children of non-affiliated women. It finds
      that mother's affiliation to any religious organization, as compared with non
      affiliation, has a significant positive effect on child survival net of education
      and other socio-demographic factors. When the effects of affiliation to specific
      denominational groups are examined, only affiliation to the Catholic or
      mainstream Protestant churches and affiliation to Apostolic churches are
      significantly associated with improved child survival. It is argued that the
      advantages of these groups may be achieved through different mechanisms: the
      favourable effect on child survival of having mothers affiliated to the Catholic
      or mainstream Protestant churches is probably due to these churches' stronger
      connections to the health sector, while the beneficial effect of having an
      Apostolic mother is probably related to strong social ties and mutual support in
      Apostolic congregations. The findings thus shed light on multiple pathways
      through which organized religion can affect child health and survival in sub
      Saharan Africa and similar developing settings.

PMID- 22856882
TI  - The bZIP dimer localizes at DNA full-sites where each basic region can
      alternately translocate and bind to subsites at the half-site.
AB  - Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1
      or CRE site show how each GCN4 basic region binds to a 4 bp cognate half-site as
      a single DNA target; however, this may not always fully describe how bZIP
      proteins interact with their target sites. Previously, we showed that the GCN4
      basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR) and that
      5H-LR comprises two 4 bp subsites, TTGC and TGCG, which individually are also
      target sites of the basic region. In this work, we explore how the basic region
      interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER
      molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing
      5H-LR to investigate in silico the interface between the basic region and 5H-LR.
      We also performed in vitro investigation of bZIP-DNA interactions at a number of
      full-sites that contain 5H-LR versus either subsite: we analyzed results from
      DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from
      EMSA titrations to quantify binding affinities. Our computational and
      experimental results together support a highly dynamic DNA-binding model: when a
      bZIP dimer localizes to its target full-site, the basic region can alternately
      recognize either subsite as a distinct target at 5H-LR and translocate between
      the subsites, potentially by sliding and hopping. This model provides added
      insights into how alpha-helical DNA-binding domains of transcription factors can
      localize to their gene regulatory sequences in vivo.

PMID- 22856883
TI  - A common genetic basis to the origin of the leaf economics spectrum and metabolic
      scaling allometry.
AB  - Many facets of plant form and function are reflected in general cross-taxa
      scaling relationships. Metabolic scaling theory (MST) and the leaf economics
      spectrum (LES) have each proposed unifying frameworks and organisational
      principles to understand the origin of botanical diversity. Here, we test the
      evolutionary assumptions of MST and the LES using a cross of two genetic variants
      of Arabidopsis thaliana. We show that there is enough genetic variation to
      generate a large fraction of variation in the LES and MST scaling functions. The
      progeny sharing the parental, naturally occurring, allelic combinations at two
      pleiotropic genes exhibited the theorised optimum 3/4 allometric scaling of
      growth rate and intermediate leaf economics. Our findings: (1) imply that a few
      pleiotropic genes underlie many plant functional traits and life histories; (2)
      unify MST and LES within a common genetic framework and (3) suggest that observed
      intermediate size and longevity in natural populations originate from stabilising
      selection to optimise physiological trade-offs.

PMID- 22856884
TI  - Vitreous surgery impact in glaucoma development in liver transplanted familial
      amyloidosis ATTR V30M Portuguese patients.
AB  - PURPOSE: Familial amyloidosis with polyneuropathy (FAP) sometimes courses with
      vitreous amyloid. The aim of this study was to evaluate the incidence of glaucoma
      after vitrectomy in FAP patients. METHODS: A total of 79 eyes of 42 liver
      transplanted FAP patients and 16 eyes of 16 non-FAP patients with rhegmatogenous
      retina detachment were collected. The patients were divided in to three groups:
      Group I - FAP patients with vitreous opacities submitted to vitrectomy, Group II 
      FAP patients without vitreous opacities and not submitted to vitrectomy and,
      Group III - non-FAP patients with rhegmatogenous retinal detachment submitted to
      vitrectomy. The Group I was subdivided into: Ia - "complete" vitrectomy; Ib -
      "incomplete" vitrectomy. The onset of glaucoma was considered when the
      intraocular pressure level was higher than 21 mmHg, with concomitant visual field
      abnormalities and optic nerve cupping. RESULTS: Post vitrectomy glaucoma was more
      frequent in Group I (56.1%) than in Group III (12.5%) and in Group II (10.5%). We
      observed a higher incidence of glaucoma in the Ia than in the Ib subgroup (86.4
      vs. 21.1%) and earlier appearance in subgroup Ia (7.9 +/- 3.6 vs. 39.5 +/- 6.6
      months). CONCLUSION: Vitrectomy induced the development of glaucoma in FAP
      patients.

PMID- 22856885
TI  - Antibiotic catheter locks in the treatment of tunneled hemodialysis catheter
      related blood stream infection.
AB  - We prospectively examined the efficacy of systemic antibiotics and antibiotic
      catheter locks for the treatment of tunneled hemodialysis catheter related blood
      stream infections (CRBSI). Patients with clinical signs of tunnel or metastatic
      infection were excluded. All patients with suspected CRBSI were treated
      empirically with systemic antibiotics at the onset of symptoms before final
      culture and susceptibility results were available. Once the organism was
      identified, antibiotics treatment was tailored and antibiotic catheter locks were
      instilled after each dialysis treatment. Clearance of infection was documented by
      negative surveillance cultures after completion of antibiotic course. Out of 46
      episodes of CRBSI; 16 were due to gram positive organisms, 22 were due to gram
      negative organisms, and 8 were polymicrobial (>=2 organisms) infections. 19 cases
      required removal of dialysis catheter. Antibiotic lock protocol was successful
      for eradicating infection in 27 of 46 episodes (59%). The likelihood of a
      clinical cure was identical in both gram-positive and gram-negative infections
      (63% and 62% respectively). Antibiotic lock protocol remains an option in the
      treatment of clinically stable patients with CRBSI; however, success rate of this
      protocol in eradicating the infection is modest.

PMID- 22856886
TI  - Fullerene-enhanced accumulation of p,p'-DDE in agricultural crop species.
AB  - The effect of C(60) fullerene exposure on the accumulation of
      dichlorodiphenyldichloroethylene (p,p'-DDE; DDT metabolite) by Cucurbita pepo L.
      (zucchini), Glycine max L. (soybean), and Solanum lycopersicum L. (tomato) was
      determined. The plants were grown in 125 mL jars of vermiculite amended with 0 or
      40 mg of C(60) fullerenes. Prior to planting, the jars were amended with 40 mL
      solution containing 100 ng/mL of p,p'-DDE with 0 or 100 mg/L humic acid. During
      three weeks of growth, plants were watered with the same p,p'-DDE containing
      solutions. Total shoot p,p'-DDE levels in nonfullerene exposed tomato, soybean,
      and zucchini were 26.9, 131, and 675 ng, respectively; total root DDE content for
      the three plants was 402, 5970, and 5830 ng, respectively. Fullerenes increased
      the shoot p,p'-DDE content of zucchini by 29%; contaminant levels in soybean
      shoots were decreased by 48% but tomato shoot content was unaffected. The root
      and total plant p,p'-DDE content of all three species was significantly increased
      by fullerene exposure; enhanced contaminant uptake ranged from 30 to 65%. Humic
      acid, regardless of fullerene presence or plant type, significantly decreased the
      p,p'-DDE uptake. Fullerenes were detected in the roots of all plants but were not
      detected in plant shoots in the initial study. In a follow up study with zucchini
      designed to maximize biomass for extraction, over half the analyzed stems
      contained fullerenes at 60.5 to 4490 ng/g. These findings show that the carbon
      based nanomaterials may significantly alter the accumulation and potentially the
      toxicity of cocontaminants in agricultural systems.

PMID- 22856887
TI  - Electrostatic interactions and aqueous two-phase separation modes of aqueous
      mixed oppositely charged surfactants system.
AB  - Electrostatic interactions play an important role in setting the aqueous two
      phase separation behaviors of mixtures of oppositely charged surfactants. The
      aqueous mixture of cetyltrimethylammonium bromide (CTAB) and sodium
      dodecylsulfonate (AS) is actually a five-component system, comprised of CTAB, AS,
      complex salt (cetyltrimethylammonium dodecylsulfonate, abbreviated as CTA(+)AS(
      )), NaBr, and water. In the three-dimensional pyramid phase diagram, the aqueous
      two-phase region with excess AS or with excess CTAB extends successively from the
      region very near to the NaBr-H2O line through the CTAB-AS-H2O conventional mixing
      plane to the CTA(+)AS(-)-AS-H2O side plane or to the CTA(+)AS(-)-CTAB-H2O side
      plane, respectively. Large or small molar ratios between the counterions and
      their corresponding surfactant ions for oppositely charged surfactants located in
      the NaBr side or the CTA(+)AS(-) side of the pyramid imply strong or weak
      electrostatic screening. Electrostatic screening of counterions alters the
      electrostatic attractions between the oppositely charged head groups or the
      electrostatic repulsions between the like-charged head groups in excess, and the
      electrostatic free energy of aggregation thus affects the aqueous two-phase
      separation modes. Composition analysis, rheological property investigation, and
      TEM images suggest that there are two kinds of aqueous two-phase systems (ATPSs).
      On the basis of these experimental results and Kaler's cell model, two kinds of
      phase separation modes were proposed. Experimental results also indicate that all
      of the top phases are surfactant-rich, and all of the bottom phases are
      surfactant-poor; the density difference between the top phase and the bottom
      phase in one ATPS is very small; the interfacial tension (sigma) of the ATPS is
      ultralow. 

PMID- 22856888
TI  - Cancer mortality following radiotherapy for benign gynecologic disorders.
AB  - The purpose of this study is to quantify cancer mortality in relationship to
      organ-specific radiation dose among women irradiated for benign gynecologic
      disorders. Included in this study are 12,955 women treated for benign gynecologic
      disorders at hospitals in the Northeastern U.S. between 1925 and 1965; 9,770
      women treated by radiation and 3,186 women treated by other methods. The average
      age at treatment was 45.9 years (range, 13-88 years), and the average follow-up
      period was 30.1 years (maximum, 69.9 years). Radiation doses to organs and active
      bone marrow were reconstructed by medical physicists using original radiotherapy
      records. The highest doses were received by the uterine cervix (median, 120 Gy)
      and uterine corpus (median, 34 Gy), followed by the bladder, rectum and colon
      (median, 1.7-7.2 Gy), with other abdominal organs receiving median doses <=1 Gy
      and organs in the chest and head receiving doses <0.1 Gy. Standardized mortality
      rate ratios relative to the general U.S. population were calculated. Radiation
      related risks were estimated in internal analyses using Poisson regression
      models. Mortality was significantly elevated among irradiated women for cancers
      of the uterine corpus, ovary, bladder, rectum, colon and brain, as well as for
      leukemia (exclusive of chronic lymphocytic leukemia) but not for cancer of the
      cervix, Hodgkin or non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic
      leukemia. Evidence of a dose-response was seen for cancers of the ovary [excess
      relative risk (ERR) = 0.31/Gy, P < 0.001], bladder (ERR = 0.21/Gy, P = 0.02) and
      rectum (ERR = 0.23/Gy, P = 0.05) and suggested for colon (ERR = 0.09/Gy, P =
      0.10), but not for cancers of the uterine corpus or brain nor for non-chronic
      lymphocytic leukemia. Relative risks of mortality due to cancers of the stomach,
      pancreas, liver and kidney were close to 1.0, with no evidence of dose-response
      over the range of 0-1.5 Gy. Breast cancer was not significantly associated with
      dose to the breast or ovary. Mortality due to cancers of heavily irradiated
      organs remained elevated up to 40 years after irradiation. Significantly elevated
      radiation-related risk was seen for cancers of organs proximal to the radiation
      source or fields (bladder, rectum and ovary), as well as for non-chronic
      lymphocytic leukemia. Our results corroborate those from previous studies that
      suggest that cells of the uterine cervix and lymphopoietic system are relatively
      resistant to the carcinogenic effects of radiation. Studies of women irradiated
      for benign gynecologic disorders, together with studies of women treated with
      higher doses of radiation for uterine cancers, provide quantitative information
      on cancer risks associated with a broad range of pelvic radiation exposures.

PMID- 22856889
TI  - Knowledge, attitudes and practices among people with chronic hepatitis B
      attending a hepatology clinic in Malaysia: a cross sectional study.
AB  - BACKGROUND: Hepatitis B (HBV) is the leading cause of cirrhosis and
      hepatocellular carcinoma worldwide. This study assessed the knowledge, attitudes
      and practices of people with chronic HBV and the associated factors. METHODS:
      This cross-sectional study was conducted at an outpatient adult hepatology clinic
      at a tertiary hospital in Kuala Lumpur. A self-administered questionnaire was
      administered on a one-to-one basis to assess knowledge, attitudes, and lifestyle
      practices of people with chronic HBV. RESULTS: The response rate was 89% (n =
      483/543). Participants had a mean age of 46.3 (+/-14.7) years and the mean
      duration of HBV from time of diagnosis was 12.2 (+/-8.8) years. The mean
      knowledge score was 12.57/20 (standard deviation: +/-4.4, range: 0-19).
      Participants aged 30-39 years, with higher educational attainment, employed in
      professional jobs, longer duration of diagnosis and those without cirrhosis had
      significantly higher knowledge scores. Age, education level and duration of
      diagnosis were significant predictors of the knowledge score on standard multiple
      regression analysis. More than half of the participants were worried of spreading
      HBV infection to family and friends and worried since the diagnosis. A third of
      the participants (33.5%) were embarrassed to reveal their diagnosis to the public
      but most of them (93.6%) would inform their family. Those who reported feeling
      worried since their diagnosis were more likely to be middle-aged, of Malay
      ethnicity, have shorter duration of diagnosis of less than 10 years and have
      received therapy. About half of the participants (50.6%) did not share dining
      utensils and the majority (93.2%) believed that HBV can be transmitted by sharing
      of eating and drinking utensils. Older patients were significantly less likely to
      share utensils. Those who felt worried since diagnosis had significant higher
      knowledge of HBV. CONCLUSION: The findings highlight the stigma and
      misconceptions that still exist among the HBV patients. More patient and public
      education about HBV and its prevention are essential to increase awareness and to
      demystify the disease.

PMID- 22856890
TI  - Spatially resolved Raman spectroelectrochemistry of solid-state
      polythiophene/viologen memory devices.
AB  - A three terminal molecular memory device was monitored with in situ Raman
      spectroscopy during bias-induced switching between two metastable states having
      different conductivity. The device structure is similar to that of a
      polythiophene field effect transistor, but ethylviologen perchlorate was added to
      provide a redox counter-reaction to accompany polythiophene redox reactions. The
      conductivity of the polythiophene layer was reversibly switched between high and
      low conductance states with a "write/erase" (W/E) bias, while a separate readout
      circuit monitored the polymer conductance. Raman spectroscopy revealed reversible
      polythiophene oxidation to its polaron form accompanied by a one-electron
      viologen reduction. "Write", "read", and "erase" operations were repeatable, with
      only minor degradation of response after 200 W/E cycles. The devices exhibited
      switching immediately after fabrication and did not require an "electroforming"
      step required in many types of memory devices. Spatially resolved Raman
      spectroscopy revealed polaron formation throughout the polymer layer, even away
      from the electrodes in the channel and drain regions, indicating that thiophene
      oxidation "propagates" by growth of the conducting polaron form away from the
      source electrode. The results definitively demonstrate concurrent redox reactions
      of both polythiophene and viologen in solid-state devices and correlate such
      reactions with device conductivity. The mechanism deduced from spectroscopic and
      electronic monitoring should guide significant improvements in memory
      performance.

PMID- 22857001
TI  - Steric effects in the tuning of the diastereoselectivity of the intramolecular
      free-radical cyclization to an olefin as exemplified through the synthesis of a
      carba-pentofuranose scaffold.
AB  - Two free-radical cyclization reactions with the radical at the chiral C4 of the
      pentose sugar and the intramolecularly C1-tethered olefin (on radical precursors
      8 and 17) gave a new diastereospecific C4-C8 bond in
      dimethylbicyclo[2.2.1]heptane 9, whereas the new C4-C7 bond in 7-methyl-2
      oxabicyclo[2.2.1]heptanes 18a/18b gave trans and cis diastereomers, in which the
      chirality of the C4 center is fully retained as that of the starting material. It
      has been shown how the chemical nature of the fused carba-pentofuranose
      scaffolds, dimethylbicyclo[2.2.1]heptane 9 vis-a-vis 7-methyl-2
      oxabicyclo[2.2.1]heptanes 18a/18b (C7-Me in the former versus 2-O- in the
      latter), dictates the stereochemical outcome both at the Grignard reaction step
      as well as in the free-radical ring-closure reaction. The formation of pure 1,8
      trans-bicyclo[2.2.1]heptane 9 from 8 suggests that the boat-like transition state
      is favored due to the absence of steric clash of the bulky 1(S)-O-p-methoxybenzyl
      (PMB) and 7(R)-Me substituents (both in the alpha-face) with that of the 8(R)
      CH(2)(*) radical in the beta-face. The conversion of 17 -> 18a-7(S) and 18b-7(R)
      in 6:4 ratio shows that the participation of both the chair- and the boat-like
      transition states is likely.

PMID- 22857000
TI  - Targeting filamin A reduces K-RAS-induced lung adenocarcinomas and endothelial
      response to tumor growth in mice.
AB  - BACKGROUND: Many human cancer cells express filamin A (FLNA), an actin-binding
      structural protein that interacts with a diverse set of cell signaling proteins,
      but little is known about the biological importance of FLNA in tumor development.
      FLNA is also expressed in endothelial cells, which may be important for tumor
      angiogenesis. In this study, we defined the impact of targeting Flna in cancer
      and endothelial cells on the development of tumors in vivo and on the
      proliferation of fibroblasts in vitro. METHODS: First, we used a Cre-adenovirus
      to simultaneously activate the expression of oncogenic K-RAS and inactivate the
      expression of Flna in the lung and in fibroblasts. Second, we subcutaneously
      injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells.
      RESULTS: Knockout of Flna significantly reduced K-RAS-induced lung tumor
      formation and the proliferation of oncogenic K-RAS-expressing fibroblasts, and
      attenuated the activation of the downstream signaling molecules ERK and AKT.
      Genetic deletion of endothelial FLNA in mice did not impact cardiovascular
      development; however, knockout of Flna in endothelial cells reduced subcutaneous
      fibrosarcoma growth and vascularity within tumors. CONCLUSIONS: We conclude that
      FLNA is important for lung tumor growth and that endothelial Flna impacts local
      tumor growth. The data shed new light on the biological importance of FLNA and
      suggest that targeting this protein might be useful in cancer therapeutics.

PMID- 22857002
TI  - Kiricephalus coarctatus in an Eastern Indigo Snake (Drymarchon couperi);
      endoscopic removal, identification, and phylogeny.

PMID- 22857003
TI  - Therapeutic drug monitoring: a way to improve long-term immunological balance?

PMID- 22857004
TI  - Bacterial pathogens: from natural ecosystems to human hosts.
AB  - The analysis of the genomes of bacterial pathogens indicates that they have
      acquired their pathogenic capability by incorporating different genetic elements
      through horizontal gene transfer. The ancestors of virulent bacteria, as well as
      the origin of virulence determinants, lay most likely in the environmental
      microbiota. Studying the role that these determinants may have in non-clinical
      ecosystems is thus of value for understanding in detail the evolution and the
      ecology of bacterial pathogens. In this article, I propose that classical
      virulence determinants might be relevant for basic metabolic processes (for
      instance iron-uptake systems) or in modulating prey/predator relationships
      (toxins) in natural, non-infective ecosystems. The different role that horizontal
      gene transfer and mutation may have in the evolution of bacterial pathogens
      either for their speciation or in short-sighted evolution processes is also
      discussed.

PMID- 22857005
TI  - Pathogen and host genotype differently affect pathogen fitness through their
      effects on different life-history stages.
AB  - BACKGROUND: Adaptation of pathogens to their hosts depends critically on factors
      affecting pathogen reproductive rate. While pathogen reproduction is the end
      result of an intricate interaction between host and pathogen, the relative
      contributions of host and pathogen genotype to variation in pathogen life history
      within the host are not well understood. Untangling these contributions allows us
      to identify traits with sufficient genetic variation for selection to act and to
      identify mechanisms of coevolution between pathogens and their hosts. We
      investigated the effects of pathogen and host genotype on three life-history
      components of pathogen fitness; infection efficiency, latent period, and
      sporulation capacity, in the oat crown rust fungus, Puccinia coronata f.sp.
      avenae, as it infects oats (Avena sativa). RESULTS: We show that both pathogen
      and host genotype significantly affect total spore production but do so through
      their effects on different life-history stages. Pathogen genotype has the
      strongest effect on the early stage of infection efficiency, while host genotype
      most strongly affects the later life-history stages of latent period and
      sporulation capacity. In addition, host genotype affected the relationship
      between pathogen density and the later life-history traits of latent period and
      sporulation capacity. We did not find evidence of pathogen-by-host genotypic
      (GxG) interactions. CONCLUSION: Our results illustrate mechanisms by which
      variation in host populations will affect the evolution of pathogen life history.
      Results show that different pathogen life-history stages have the potential to
      respond differently to selection by host or pathogen genotype and suggest
      mechanisms of antagonistic coevolution. Pathogen populations may adapt to host
      genotypes through increased infection efficiency while their plant hosts may
      adapt by limiting the later stages of pathogen growth and spore production within
      the host.

PMID- 22857006
TI  - Mutation analysis in Chinese patients with Cornelia de Lange syndrome.
AB  - AIMS: Cornelia de Lange syndrome (CdLS) is a dominant multisystem developmental
      disorder and related to mutations of the NIPBL, SMC1A, and SMC3 genes. So far,
      there has been no report of a mutation analysis in Chinese patients with CdLS,
      while 12 cases have been clinically described. In the present study, we tried to
      search for pathogenic mutations of the NIPBL, SMC1A, and SMC3 genes in four
      patients with CdLS from four unrelated Chinese families. RESULTS: The mutational
      analysis of the NIPBL, SMC1A, and SMC3 genes by direct sequencing revealed a
      heterozygous splice-site mutation c.4321G>T(p.V1441L) at exon 20 of NIPBL in
      proband 2 and a novel heterozygous splice-site mutation c.6589+5G>C at intron 38
      of NIPBL in proband 3, which was showed by reverse transcription polymerase chain
      reaction to generate both the full-length and an alternatively spliced transcript
      with an exon 38 deletion. CONCLUSIONS: This is the first report of the mutation
      analysis of NIPBL in China and our findings both expand the mutation spectrum of
      NIPBL and provide data for further understanding of the diverse and variable
      effects of NIPBL mutations.

PMID- 22857007
TI  - An investigation into the seroprevalence of Toxoplasma gondii, Bartonella spp.,
      feline immunodeficiency virus (FIV), and feline leukaemia virus (FeLV) in cats in
      Addis Ababa, Ethiopia.
AB  - Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline
      immunodeficiency virus (FIV), and feline leukaemia virus (FeLV) are
      immunosuppressive viruses of cats that can affect T. gondii oocyst shedding. In
      this study, the prevalence of antibodies to T. gondii, Bartonella spp., FIV, as
      well as FeLV antigens were determined in sera from feral cats (Felis catus) from
      Addis Ababa, Ethiopia. Using the modified agglutination test, IgG antibodies to
      T. gondii were found in 41 (85.4%) of the 48 cats with titres of 1:25 in one,
      1:50 in one, 1:200 in six, 1:400 in six, 1:800 in six, 1:1600 in eight, and
      1:3200 in 13 cats. Toxoplasma gondii IgM antibodies were found in 11/46 cats
      tested by ELISA, suggesting recent infection. Antibodies to Bartonella spp. were
      found in five (11%) of 46 cats tested. Antibodies to FIV or FeLV antigen were not
      detected in any of the 41 cats tested. The results indicate a high prevalence of
      T. gondii and a low prevalence of Bartonella spp. infection in cats in Ethiopia.

PMID- 22857008
TI  - Effects of the antimycobacterial compound 2-phenoxy-1-phenylethanone on rat
      hepatocytes and formation of metabolites.
AB  - CONTEXT: Neolignans are usually dimers formed by oxidative coupling of allyl and
      propenyl phenols, and the neolignan analogue, 2-phenoxy-1-phenylethanone (LS-2)
      is a promising antimycobacterial compound showing very weak cytotoxicity in
      mammalian cells and lack of acute toxicity in murine models. OBJECTIVES: To
      investigate the mechanism of action of LS-2 in rat hepatocytes by evaluating the
      activity levels of enzymes related to oxidation status and drug-metabolizing
      activity. MATERIALS AND METHODS: Hepatocytes were treated with LS-2 from 0.05 up
      to 1 mM, for 24 and 48 h, and reduced glutathione (GSH), lipid peroxidation and
      cytochrome P450 enzyme (CYP450) activity were assayed. A homologous series of
      phenoxazone ethers were used as substrates to measure the enzymatic profile. The
      biotransformation of LS-2 was studied in hepatocytes by gas chromatography-mass
      spectrometry (GC-MS) for detection and analysis of possible metabolites. RESULTS:
      Hepatocytes treated with LS-2 up to 1 mM for 24 or 48 h did not induce the
      formation of GSH and lipid peroxidation. O-Dealkylation activities of the
      isoenzymes CYP4501A1, CYP4501A2, CYP4502B1 and CYP4502B2 were also not detected
      in the hepatocytes treated with LS-2 for 24 or 48 h. DISCUSSION AND CONCLUSION:
      The results indicate that LS-2 or its two detected metabolites, 2-phenoxy-1
      phenylethanol and 2,4-(2-hydroxy-2-phenylethoxy)phenol, are not cytotoxic to rat
      hepatocytes. These compounds maintain a balance between the production of pro
      oxidant agents and their respective antioxidant systems. The data show that
      enzymes related to oxidation status and drug-metabolizing activities are not
      involved in the mechanism of action of LS-2.

PMID- 22857009
TI  - Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report.
AB  - BACKGROUND: With an increasing incidence of congenital heart defects (CHDs) in
      recent years, genotype-phenotype correlation and array-based methods have
      contributed to the genome-wide analysis and understanding of genetic variations
      in the CHD population. Here, we report a copy number deletion of chromosomal
      14q23.1 in a female fetus with complex congenital heart defects. This is the
      first description of DAAM1 gene deletion associated with congenital heart
      anomalies. CASE PRESENTATION: Compared with the control population, one CHD fetus
      showed a unique copy number deletion of 14q23.1, a region that harbored DAAM1 and
      KIAA0666 genes. CONCLUSIONS: Results suggest that the copy number deletion on
      chromosome 14q23.1 may be critical for cardiogenesis. However, the exact
      relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the
      onset of CHD is yet to be determined.

PMID- 22857010
TI  - Activity-dependent phosphorylation of dynamin 1 at serine 857.
AB  - Dynamin 1 is thought to mediate synaptic transmission through interactions with
      multiple endocytic accessory proteins in a phosphorylation-dependent manner.
      Previously, we have shown that DYRK1A, a chromosome 21-encoded kinase implicated
      in the mental retardation of Down syndrome, phosphorylates primarily serine 857
      (S857) in the proline-rich domain, found only in 1xa, one of the alternative C
      terminal splicing isoforms of dynamin 1. Dynamin 1xa and 1xb isoforms are able to
      assemble into heterologous complexes and are coregulated by DYRK1A
      phosphorylation in binding to amphiphysin in vitro. To help in assessing the
      physiological significance of S857 phosphorylation, we developed a
      semiquantitative method for measuring the cellular level of phospho-S857 (pS857).
      Dynamin 1xa is highly phosphorylated at S857 in resting hippocampal neurons and
      in a hippocampal cell line, with >60% of all endogenous protein phosphorylated at
      this residue. In the hippocampus, the level of pS857 is dynamically controlled by
      synaptic stimulations with the involvement of Ca(2+)/calcineurin and AMPA/kainate
      receptors. Immunofluorescence staining shows that pS857 is found in the soma and
      throughout the entire length of apical dendrites in resting pyramidal neurons.
      Neuronal stimulation in the Schaffer collateral pathway promotes pS857
      dephosphorylation in distal areas of apical dendrites, the region forming
      synapses with the impinging axons of Schaffer collateral. In summary, our results
      support the conclusion that S857 phosphorylation is a physiological event and its
      level is modulated by neuronal activity in nerve terminals.

PMID- 22857012
TI  - Probing ligand-binding modes and binding mechanisms of benzoxazole-based amide
      inhibitors with soluble epoxide hydrolase by molecular docking and molecular
      dynamics simulation.
AB  - Soluble epoxide hydrolase (sEH) has become a new therapeutic target for treating
      a variety of human diseases. The inhibition of human sEH hydrolase activity was
      studied by molecular docking and molecular dynamics (MD) simulation techniques. A
      set of six benzoxazole-based amide inhibitors binding to sEH has been studied
      through molecular docking, MD simulation, free energy calculations, and energy
      decomposition analysis. On the basis of molecular mechanics-generalized
      Born/surface area (MM-GB/SA) computation and normal-mode analysis (NMA), the
      obtained results indicate that the rank of calculated binding free energies
      (DeltaDeltaGTOT) of these inhibitors is in excellent agreement with that of
      experimental bioactivity data (IC50). The correlation coefficient (r(2)) between
      the predicted DeltaDeltaGTOT and IC50 is 0.88. van der Waals energies are the
      largest component of the total energies, and the entropy changes play an
      indispensable role in determining the DeltaDeltaGTOT. Rational binding modes were
      discussed and determined by the docking results and binding free energies. The
      free energy decomposition of each residue reveals that the residue Trp334
      dominates the most binding free energies among all residues and that the
      activities for these molecules to the sEH are not decided by hydrogen bonds or a
      certain residue but by the common effect of multiple side chains in the active
      site. 

PMID- 22857011
TI  - Photocured biodegradable polymer substrates of varying stiffness and microgroove
      dimensions for promoting nerve cell guidance and differentiation.
AB  - Photocross-linkable and biodegradable polymers have great promise in fabricating
      nerve conduits for guiding axonal growth in peripheral nerve regeneration. Here,
      we photocross-linked two poly(epsilon-caprolactone) triacrylates (PCLTAs) with
      number-average molecular weights of ~7000 and ~10,000 g mol(-1) into substrates
      with parallel microgrooves. Cross-linked PCLTA7k was amorphous and soft, while
      cross-linked PCLTA10k was semicrystalline with a stiffer surface. We employed
      different dimensions of interests for the parallel microgrooves, that is, groove
      widths of 5, 15, 45, and 90 MUm and groove depths of 0.4, 1, 5, and 12 MUm. The
      behaviors of rat Schwann cell precursor line (SpL201) cells with the glial nature
      and pheochromocytoma (PC12) cells with the neuronal nature were studied on these
      microgrooved substrates, showing distinct preference to the substrates with
      different mechanical properties. We found different threshold sensitivities of
      the two nerve cell types to topographical features when their cytoskeleton and
      nuclei were altered by varying the groove depth and width. Almost all of the
      cells were aligned in the narrowest and deepest microgrooves or around the edge
      of microgrooves. Oriented SpL201 cell movement had a higher motility as compared
      to unaligned ones. After forskolin treatment, SpL201 cells demonstrated
      significantly upregulated S-100 and O4 on stiffer substrates or narrower
      microgrooves, suggesting more differentiation toward early Schwann cells (SCs).
      PC12 neurites were oriented with enhanced extension in narrower microgrooves. The
      present results not only improve our fundamental understanding on nerve cell
      substrate interactions, but also offer useful conduit materials and appropriate
      feature dimensions to foster guidance for axonal growth in peripheral nerve
      regeneration.

PMID- 22857013
TI  - CO2 copolymers from epoxides: catalyst activity, product selectivity, and
      stereochemistry control.
AB  - The use of carbon dioxide as a carbon source for the synthesis of organic
      chemicals can contribute to a more sustainable chemical industry. Because CO(2)
      is such a thermodynamically stable molecule, few effective catalysts are
      available to facilitate this transformation. Currently, the major industrial
      processes that convert CO(2) into viable products generate urea and
      hydroxybenzoic acid. One of the most promising new technologies for the use of
      this abundant, inexpensive, and nontoxic renewable resource is the alternating
      copolymerization of CO(2) and epoxides to provide biodegradable polycarbonates,
      which are highly valuable polymeric materials. Because this process often
      generates byproducts, such as polyether or ether linkages randomly dispersed
      within the polycarbonate chains and/or the more thermodynamically stable cyclic
      carbonates, the choice of catalyst is critical for selectively obtaining the
      expected product.  In this Account, we outline our efforts to develop highly
      active Co(III)-based catalysts for the selective production of polycarbonates
      from the alternating copolymerization of CO(2) with epoxides. Binary systems
      consisting of simple (salen)Co(III)X and a nucleophilic cocatalyst exhibited high
      activity under mild conditions even at 0.1 MPa CO(2) pressure and afforded
      copolymers with >99% carbonate linkages and a high regiochemical control (~95%
      head-to-tail content). Discrete, one-component (salen)Co(III)X complexes bearing
      an appended quaternary ammonium salt or sterically hindered Lewis base showed
      excellent activity in the selectively alternating copolymerization of CO(2) with
      both aliphatic epoxides and cyclohexene oxide at high temperatures with low
      catalyst loading and/or low pressures of CO(2). Binary or one-component catalysts
      based on unsymmetric multichiral Co(III) complexes facilitated the efficient
      enantioselective copolymerization of CO(2) with epoxides, providing aliphatic
      polycarbonates with >99% head-to-tail content. These systems were also very
      efficient in catalyzing the terpolymerization of cyclohexene oxide, propylene
      oxide and CO(2). The resulting terpolymer had a single glass-transition
      temperature and a single thermolysis peak.  This Account also provides a thorough
      mechanistic understanding of the high activities, excellent selectivities, and
      unprecedented stereochemical control of these Co(III)-based catalysts in the
      production of CO(2) copolymers . The catalysis occurs through a cooperative
      monometallic mechanism, in which the Lewis acidic Co(III) ion serves as
      electrophile to activate then epoxide and the nucleophilic counterion or
      cocatalyst serves as a nucleophile to initiate polymer-chain growth. The high
      activity and excellent regioselectivity observed in the epoxide ring-opening
      reactions results from epoxide activation through the moderate electrophilicity
      of the Co(III) ion, the fast insertion of CO(2) into the Co-O bond, and the
      facile dissociation of the propagating carboxylate species from the central metal
      ion. The reversible intra- or intermolecular Co-O bond formation and dissociation
      helps to stabilize the active Co(III) species against reversion to the inactive
      Co(II) ion. We also describe our laboratory's recent preparation of the first
      crystalline CO(2)-based polymer via highly stereospecific copolymerization of
      CO(2) and meso-cyclohexene oxide and the selective synthesis of perfectly
      alternating polycarbonates from the coupling of CO(2) with epoxides bearing an
      electron-withdrawing group.

PMID- 22857014
TI  - A pooled analysis of thyroid cancer incidence following radiotherapy for
      childhood cancer.
AB  - Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to
      radiation is a known thyroid carcinogen; however, data are limited for the
      evaluation of radiation dose-response at high doses, modifiers of the dose
      response relationship and joint effects of radiotherapy and chemotherapy. To
      address these issues, we pooled two cohort and two nested case-control studies of
      childhood cancer survivors including 16,757 patients, with 187 developing primary
      thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for
      thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin
      were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in
      patients without radiotherapy, and declined with greater radiation dose (RR
      trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs
      increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30
      Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10
      Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing
      age at exposure (P < 0.01), but did not vary with attained age or time-since
      exposure, remaining elevated 25+ years after exposure. Gender and number of
      treatments did not modify radiation effects. Thyroid cancer risks remained
      elevated many decades following radiotherapy, highlighting the need for continued
      follow up of childhood cancer survivors.

PMID- 22857015
TI  - Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: is it
      better than three dimensional conformal radiotherapy?
AB  - BACKGROUND: Cure rate of early Hodgkin Lymphoma are high and avoidance of late
      toxicities is of paramount importance. This comparative study aims to assess the
      normal tissue sparing capability of intensity-modulated radiation therapy (IMRT)
      versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of
      dose-volume parameters and normal tissue complication probability (NTCP) for
      different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients.
      METHODS: Ten HL patients were actually treated with 3D-CRT and all treatments
      were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus,
      heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose
      volume histograms generated by TPS were analyzed to predict the NTCP for the
      considered organs at risk, according to different endpoints. RESULTS: Regarding
      dose-volume parameters no statistically significant differences were recorded for
      heart and origin of coronary arteries. We recorded statistically significant
      lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1
      p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and
      lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to
      the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with
      IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p =
      0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found,
      respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs
      20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10:
      2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right
      breast.) As for the NTCP, our data point out that IMRT is not always likely to
      significantly increase the NTCP to OARs. CONCLUSIONS: In HL male patients IMRT
      seems feasible and accurate while for women HL patients IMRT should be used with
      caution.

PMID- 22857016
TI  - Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of
      lung cancer in nude rats.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Pulmonary
      anticancer therapy might offer several advantages over systemic delivery, leading
      to an increased exposure of the lung tumor to the drug, while minimizing side
      effects, due to regional containment. Here, we studied if a combination of
      inhalation therapy and drug targeting holds potential as an even more efficient
      lung cancer therapy. METHODS: Transferrin (Tf )-conjugated PEG liposomes loaded
      with doxorubicin (DOX) were administered using an intracorporeal nebulizing
      catheter to an orthotopic lung cancer model established in athymic Rowett nude
      rats. Different DOX formulations and doses (0.2 and 0.4 mg/kg) were tested and
      the influence on tumor progression and life span of rats was evaluated in
      comparison with the i.v. administration of Tf-PEG-liposomes loaded with DOX at a
      therapeutic dose of 2 mg/kg. RESULTS: Rats in the untreated control group showed
      significant weight loss 2 weeks after tumor induction and died between days 19
      and 29. Lungs of these animals showed multiple foci of neoplastic deposits,
      ranging up to 20 mm replacing the entire lobe. Empty Tf-liposomes showed a
      significant effect on survival time. This might be caused by the secondary
      cytotoxicity via stimulation of pulmonary macrophages. All animal treated
      intravenously also perished before the end of the study. No significant (p<0.05)
      improvement in survival was observed between the groups treated with aerosols of
      free drug, DOX encapsulated in plain and in Tf-modified liposomes. However, more
      animals survived in the Tf-liposome groups than in the other treatment regimes,
      and their lung tissue generally had fewer and smaller tumors. Nevertheless, the
      size of the groups, and the duration of the trial render it impossible to come to
      a definite conclusion. CONCLUSIONS: Drug targeting demonstrated potential for
      improving the aerosol treatment of lung cancer.

PMID- 22857018
TI  - Extremely short duration high-intensity training substantially improves endurance
      performance in triathletes.
AB  - High-intensity training (HIT) involving 30-s sprints is an effective training
      regimen to improve aerobic performance. We tested whether 6-s HITs can improve
      aerobic performance in triathletes. Six subelite triathletes (age, 40 +/- 9
      years; weight, 86 +/- 11 kg; body mass index, 26 +/- 3 kg.m-2) took part in cycle
      HIT and 6 endurance-trained subelite athletes (age, 36 +/- 9 years; weight, 82 +/
      11 kg; BMI, 26 +/- 3 kg.m-2) maintained their normal training routine. Before
      and after 2 weeks of HIT, involving 10 * 6-s sprints or normal activity,
      participants performed a self-paced 10-km time trial and a time to exhaustion
      test on a cycle ergometer. Finger prick blood samples were taken throughout the
      time to exhaustion test to determine blood lactate concentration. Two weeks of
      HIT resulted in a 10% decrease in self-paced 10-km time trial (p = 0.03) but no
      significant change in time to exhaustion. The time taken to reach onset of blood
      lactate accumulation (OBLA, defined as the point where blood lactate reaches 4
      mmol.L-1) was significantly increased following 2 weeks of HIT (p = 0.003). The
      change in time trial performance was correlated to the change in time taken to
      reach OBLA (R2 = 0.63; p = 0.001). We concluded that a very short duration HIT is
      a very effective training regimen to improve aerobic performance in subelite
      triathletes and this is associated with a delay in blood lactate build-up.

PMID- 22857017
TI  - Randomised controlled trial of an automated, interactive telephone intervention
      (TLC Diabetes) to improve type 2 diabetes management: baseline findings and six
      month outcomes.
AB  - BACKGROUND: Effective self-management of diabetes is essential for the reduction
      of diabetes-related complications, as global rates of diabetes escalate. METHODS:
      Randomised controlled trial. Adults with type 2 diabetes (n = 120), with HbA1c
      greater than or equal to 7.5 %, were randomly allocated (4 * 4 block randomised
      block design) to receive an automated, interactive telephone-delivered management
      intervention or usual routine care. Baseline sociodemographic, behavioural and
      medical history data were collected by self-administered questionnaires and
      biological data were obtained during hospital appointments. Health-related
      quality of life (HRQL) was measured using the SF-36. RESULTS: The mean age of
      participants was 57.4 (SD 8.3), 63% of whom were male. There were no differences
      in demographic, socioeconomic and behavioural variables between the study arms at
      baseline. Over the six-month period from baseline, participants receiving the
      Australian TLC (Telephone-Linked Care) Diabetes program showed a 0.8% decrease in
      geometric mean HbA(1c) from 8.7% to 7.9%, compared with a 0.2% HbA(1c) reduction
      (8.9% to 8.7%) in the usual care arm (p = 0.002). There was also a significant
      improvement in mental HRQL, with a mean increase of 1.9 in the intervention arm,
      while the usual care arm decreased by 0.8 (p = 0.007). No significant
      improvements in physical HRQL were observed. CONCLUSIONS: These analyses indicate
      the efficacy of the Australian TLC Diabetes program with clinically significant
      post-intervention improvements in both glycaemic control and mental HRQL. These
      observed improvements, if supported and maintained by an ongoing program such as
      this, could significantly reduce diabetes-related complications in the longer
      term. Given the accessibility and feasibility of this kind of program, it has
      strong potential for providing effective, ongoing support to many individuals
      with diabetes in the future.

PMID- 22857019
TI  - Are H-reflex and M-wave recruitment curve parameters related to aerobic capacity?
AB  - Soleus Hoffmann reflex (H-reflex) amplitude is affected by a training period and
      type and level of training are also well known to modify aerobic capacities.
      Previously, paired changes in H-reflex and aerobic capacity have been evidenced
      after endurance training. The aim of this study was to investigate possible links
      between H- and M-recruitment curve parameters and aerobic capacity collected on a
      cohort of subjects (56 young men) that were not involved in regular physical
      training. Maximal H-reflex normalized with respect to maximal M-wave
      (H(max)/M(max)) was measured as well as other parameters of the H- or M
      recruitment curves that provide information about the reflex or direct
      excitability of the motoneuron pool, such as thresholds of stimulus intensity to
      obtain H or M response (H(th) and M(th)), the ascending slope of H-reflex, or M
      wave recruitment curves (H(slp) and M(slp)) and their ratio (H(slp)/M(slp)).
      Aerobic capacity, i.e., maximal oxygen consumption and maximal aerobic power
      (MAP) were, respectively, estimated from a running field test and from an
      incremental test on a cycle ergometer. Maximal oxygen consumption was only
      correlated with M(slp), an indicator of muscle fiber heterogeneity (p < 0.05),
      whereas MAP was not correlated with any of the tested parameters (p > 0.05).
      Although higher H-reflex are often described for subjects with a high aerobic
      capacity because of endurance training, at a basic level (i.e., without training
      period context) no correlation was observed between maximal H-reflex and aerobic
      capacity. Thus, none of the H-reflex or M-wave recruitment curve parameters,
      except M(slp), was related to the aerobic capacity of young, untrained male
      subjects.

PMID- 22857130
TI  - Long-term energy and climate implications of carbon capture and storage
      deployment strategies in the US coal-fired electricity fleet.
AB  - To understand the long-term energy and climate implications of different
      implementation strategies for carbon capture and storage (CCS) in the US coal
      fired electricity fleet, we integrate three analytical elements: scenario
      projection of energy supply systems, temporally explicit life cycle modeling, and
      time-dependent calculation of radiative forcing. Assuming continued large-scale
      use of coal for electricity generation, we find that aggressive implementation of
      CCS could reduce cumulative greenhouse gas emissions (CO(2), CH(4), and N(2)O)
      from the US coal-fired power fleet through 2100 by 37-58%. Cumulative radiative
      forcing through 2100 would be reduced by only 24-46%, due to the front-loaded
      time profile of the emissions and the long atmospheric residence time of CO(2).
      The efficiency of energy conversion and carbon capture technologies strongly
      affects the amount of primary energy used but has little effect on greenhouse gas
      emissions or radiative forcing. Delaying implementation of CCS deployment
      significantly increases long-term radiative forcing. This study highlights the
      time-dynamic nature of potential climate benefits and energy costs of different
      CCS deployment pathways and identifies opportunities and constraints of
      successful CCS implementation.

PMID- 22857129
TI  - Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual
      smoking on the risk of dyslipidemia in middle-aged Japanese men.
AB  - BACKGROUND: Several genetic polymorphisms have been reported to modify the
      effects of smoking on serum lipid levels. The objective of this study was to
      investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A
      polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia
      in middle-aged Japanese subjects. METHODS: A total of 394 male subjects (age,
      53.9 +/- 7.9 years; mean +/- SD) were selected from among individuals visiting
      the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross
      sectional study assessing the joint effect of Mt5178 C/A polymorphism and
      cigarette smoking on the risk of hypo-high-density lipoprotein (HDL)
      cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or
      hypertriglyceridemia was conducted. RESULTS: For subjects with Mt5178C, the risk
      of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily
      (P for trend = 0.001). On the other hand, the association between Mt5178A
      genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the
      number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL
      cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P
      for trend = 0.017 and P for trend = 0.002, respectively). However, the
      association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or
      hypertriglyceridemia did not depend on the number of cigarettes smoked daily.
      CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modulates
      the effects of habitual smoking on the risk of dyslipidemia in middle-aged
      Japanese men.

PMID- 22857131
TI  - Editorial: Treatment of atherosclerosis as an inflammatory disease.

PMID- 22857132
TI  - In situ anomalous small-angle X-ray scattering studies of platinum nanoparticle
      fuel cell electrocatalyst degradation.
AB  - Polymer electrolyte fuel cells (PEFCs) are a promising high-efficiency energy
      conversion technology, but their cost-effective implementation, especially for
      automotive power, has been hindered by degradation of the electrochemically
      active surface area (ECA) of the Pt nanoparticle electrocatalysts. While numerous
      studies using ex situ post-mortem techniques have provided insight into the
      effect of operating conditions on ECA loss, the governing mechanisms and
      underlying processes are not fully understood. Toward the goal of elucidating the
      electrocatalyst degradation mechanisms, we have followed Pt nanoparticle growth
      during potential cycling of the electrocatalyst in an aqueous acidic environment
      using in situ anomalous small-angle X-ray scattering (ASAXS). ASAXS patterns were
      analyzed to obtain particle size distributions (PSDs) of the Pt nanoparticle
      electrocatalysts at periodic intervals during the potential cycling. Oxide
      coverages reached under the applied potential cycling protocols were both
      calculated and determined experimentally. Changes in the PSD, mean diameter, and
      geometric surface area identify the mechanism behind Pt nanoparticle coarsening
      in an aqueous environment. Over the first 80 potential cycles, the dominant Pt
      surface area loss mechanism when cycling to 1.0-1.1 V was found to be
      preferential dissolution or loss of the smallest particles with varying extents
      of reprecipitation of the dissolved species onto existing particles, resulting in
      particle growth, depending on potential profile. Correlation of ASAXS-determined
      particle growth with both calculated and voltammetrically determined oxide
      coverages demonstrates that the oxide coverage is playing a key role in the
      dissolution process and in the corresponding growth of the mean Pt nanoparticle
      size and loss of ECA. This understanding potentially reduces the complex changes
      in PSD and ECA resulting from various voltage profiles to a response dependent on
      oxide coverage.

PMID- 22857133
TI  - Viral infection of Phaeocystis globosa impedes release of chitinous star-like
      structures: quantification using single cell approaches.
AB  - Phaeocystis globosa is an ecologically important bloom-forming phytoplankton,
      which sequesters substantial amounts of inorganic carbon and can form carbon
      enriched chitinous star-like structures. Viruses infecting P. globosa (PgVs) play
      a significant regulatory role in population dynamics of the host species.
      However, the extent to which viruses alter host physiology and its carbon
      assimilation on single cell level is still largely unknown. This study
      demonstrates for the first time the impact of viral infection on carbon
      assimilation and cell morphology of individual axenic P. globosa cells using two
      single cell techniques: high resolution nanometre-scale Secondary-Ion Mass
      Spectrometry (nanoSIMS) approach and atomic force microscopy (AFM). Up until
      viral lysis (19 h post infection), the bulk carbon assimilation by infected P.
      globosa cultures was identical to the assimilation by the non-infected cultures
      (33 umol C l(-1)). However, single cell analysis showed that viral infection of
      P. globosa impedes the release of star-like structures. Non-infected cells
      transfer up to 44.5 umol C l(-1) (36%) of cellular biomass in the form of star
      like structures, suggesting a vital role in the survival of P. globosa cells. We
      hypothesize that impediment of star-like structures in infected P. globosa cells
      may inactivate viral infectivity by forming flocculants after cell lysis.
      Moreover, we show that substantial amounts of newly produced viruses (~ 68%) were
      attached to P. globosa cells prior to cell lysis. Further, we speculate that
      infected cells become more susceptible for grazing which provides potential
      reasons for the sudden disappearance of PgVs in the environment. The scenarios of
      enhanced grazing is at odds to the current perspective that viral infections
      facilitates microbial mediated processes by diverting host material away from the
      higher trophic levels.

PMID- 22857134
TI  - "That's so gay!": Examining the covariates of hearing this expression among gay,
      lesbian, and bisexual college students.
AB  - OBJECTIVE: The investigators examined the health and well-being correlates of
      hearing the popular phrase "that's so gay" among gay, lesbian, and bisexual (GLB)
      emerging adults. PARTICIPANTS: Participants were 114 self-identified GLB students
      aged 18 to 25 years. METHODS: An online survey was distributed to students at a
      large public university in the Midwest during winter 2009. RESULTS: Participants'
      social and physical well-being was negatively associated with hearing this
      phrase, specifically feeling isolated and experiencing physical health symptoms
      (ie, headaches, poor appetite, or eating problems). CONCLUSIONS: College
      professionals and student leaders must acknowledge that the phrase is a form of
      heterosexist harassment. As such, policies addressing diversity and harassment
      should address students' use of this phrase, aiming to reduce its use.
      Additionally, colleges and universities should develop practices that counteract
      poorer well-being associated with hearing the phrase.

PMID- 22857135
TI  - What college students do not know: where are the gaps in sexual health knowledge?
AB  - OBJECTIVE: This study aimed to understand the gaps in college students' knowledge
      regarding sexual health information. PARTICIPANTS: A sample of 242 participants
      enrolled in an introductory college course participated in this study in the Fall
      2009 semester. METHODS: Students participated in 1 of 2 brief interventions and
      wrote a response paper about their experience. The papers were analyzed using
      conventional content analysis for information that was new to participants by
      looking for key words that suggested learning took place. RESULTS: The findings
      indicated that the majority of participants learned new information. Most
      learning occurred regarding sexually transmitted infections (ie, types, symptoms,
      prevalence, treatment, testing) and correct condom use. There were also
      demographic differences regarding reported new information. CONCLUSIONS: Findings
      can be used to develop future sex education programs for college students by
      providing college educators with an understanding of where students lack
      knowledge of sexual health.

PMID- 22857136
TI  - Exploring the relationship between experiential avoidance, alcohol use disorders,
      and alcohol-related problems among first-year college students.
AB  - OBJECTIVE: This study explored the relationship of experiential avoidance (eg,
      the tendency to avoid, suppress, or otherwise control internal experiences even
      when doing so causes behavioral harm) to alcohol use disorders and alcohol
      related problems. PARTICIPANTS: Cross-sectional data were collected from 240
      undergraduate college students in their first year in college between December
      2009 and April 2010. METHODS: Participants completed a diagnostic interview and
      online self-report survey. RESULTS: Students with a history of alcohol abuse or
      dependence had significantly higher levels of experiential avoidance relative to
      students with no alcohol use disorder diagnosis. A hierarchical linear regression
      analysis found that experiential avoidance significantly predicted alcohol
      related problems, even after controlling for gender and psychological distress.
      Furthermore, experiential avoidance mediated the relationship of psychological
      distress to alcohol-related problems. CONCLUSIONS: These findings suggest that
      experiential avoidance may play a role in problematic alcohol use among college
      students.

PMID- 22857137
TI  - Predicting human papillomavirus vaccine intentions of college-aged males: an
      examination of parents' and son's perceptions.
AB  - OBJECTIVE: To examine male students' and their parents' human papillomavirus
      (HPV) vaccine communication in relation to males' willingness to discuss the
      vaccine with their health care provider and the likelihood of being vaccinated.
      PARTICIPANTS: Dyads (n = 111) of students and parents. METHODS: Participants
      completed a HPV vaccine survey based on the risk perception attitude framework in
      2009. RESULTS: Male students' perceived susceptibility for HPV and self-efficacy
      to talk to their provider were directly related to their intention to discuss the
      HPV vaccine, and their intention was directly related to their likelihood of
      being vaccinated. Parents' perceived self-efficacy to talk to their son and
      response efficacy of the vaccine were directly related to their intention to talk
      to their son; however, parents' intention was not related to the likelihood of
      their son being vaccinated. CONCLUSIONS: College males may benefit from HPV
      vaccine educational programs that include communication skills training to
      discuss the HPV vaccine with their parents.

PMID- 22857138
TI  - A review of human papillomavirus (HPV) infection and HPV vaccine-related
      attitudes and sexual behaviors among college-aged women in the United States.
AB  - OBJECTIVE: To identify human papillomavirus (HPV) infection and HPV vaccine
      related attitudes among college-aged women and the relationship between HPV
      vaccine uptake and subsequent sexual behaviors. METHODS: PubMed, MEDLINE, CINAHL,
      and Google Scholar searches were performed from 2006, the date after the first
      HPV vaccine became available, to present. RESULTS: Of the 13 studies identified,
      most were cross-sectional. College-aged women saw HPV infection as serious and
      had positive attitudes toward the HPV vaccine. Barriers (ie, cost, lack of
      insurance coverage) existed that prevented women from obtaining the vaccine and
      many women did not see themselves at risk for HPV. The vaccine uptake rate,
      although increasing, has been slow. CONCLUSION: College-aged women in the United
      States may need unbiased information about HPV and HPV vaccine. Studies that
      focus on risk perception and the relationship between knowledge, attitudes,
      vaccine uptake, and sexual behaviors are needed to inform interventions and
      public health programs.

PMID- 22857139
TI  - Antibiotic resistance in urinary tract infections in college students.
AB  - OBJECTIVE: To determine resistance to antibiotics of Escherichia coli in
      uncomplicated urinary tract infections (uUTIs) in female college students.
      PARTICIPANTS: Symptomatic patients presenting to a student health service from
      September 2008 to December 2009. METHODS: Clean catch midstream urine samples
      were tested for urinalysis (UA) and culture and sensitivity. RESULTS: Of 168
      students enrolled in the study, 138 had positive UA, and 94 of these grew
      >100,000 colonies/mL of E. coli. Ampicillin resistance was 31.9%, trimethoprim
      sulfamethoxazole (TMP-SMX) resistance 16.0%, ciprofloxacin resistance 4.3%,
      amoxicillin/clavulanate resistance 3.2%, and nitrofurantoin resistance 1.1%. The
      sensitivity of UA was 95.4% and the positive predictive value was 87.0% (p <=
      .001). Specificity was 77.5% and negative predictive value 92.9%. CONCLUSIONS: In
      healthy college women with uUTI symptoms, TMP-SMX should not be universally used
      for empirical therapy, whereas use of ciprofloxacin, amoxicillin/clavulanate, and
      nitrofurantoin are appropriate.

PMID- 22857140
TI  - Experience with a drug screening program at a school of pharmacy.
AB  - Substance use and abuse among pharmacy students is a concern of pharmacy schools,
      boards of pharmacy, and training sites alike. Pharmacy students must complete
      approximately 30% of their academic coursework in experiential settings such as
      community pharmacies, hospitals, and other health systems as part of any
      accredited pharmacy school's curriculum, and these training sites are starting to
      require drug testing of pharmacy students as part of their contractual agreements
      with schools of pharmacy. The authors describe the implementation of a mandatory
      random urine drug screening program at their school as well as the changes that
      occurred owing to assessment of the program. The authors report the basic results
      to date of the drug screening program. The authors also speculate on secondary
      benefits of the drug screening program. Finally, the authors describe current and
      future evaluations that they are undertaking regarding this program.

PMID- 22857141
TI  - Rates of asymptomatic nonurethral gonorrhea and chlamydia in a population of
      university men who have sex with men.
AB  - OBJECTIVES: The study determined prevalence of asymptomatic nonurethral gonorrhea
      and chlamydia in men who have sex with men (MSM) seen at the Columbia University
      Health Service for routine care. PARTICIPANTS: The study enrolled 200
      participants from March 2007 to May 2010. RESULTS: Specimens were tested using
      culture and nucleic acid amplification testing (NAAT): 3.5% (n = 7) tested
      positive for pharyngeal gonorrhea by NAAT, none were positive by culture; 3% (n =
      6) tested positive for rectal chlamydia by NAAT and 0.5% (n = 1) by culture.
      CONCLUSIONS: The incidence of pharyngeal gonorrhea and rectal chlamydia in MSM
      who visited the Columbia Health Service was similar to rates of asymptomatic
      nonurethral gonorrhea and chlamydia in studies conducted in the MSM population in
      non-university settings. This suggests that, following the Centers for Disease
      Control and Prevention guidelines, 3-site testing for MSM seen at the Columbia
      clinic is indicated. NAAT is more sensitive than culture for nonurethral
      gonorrhea and chlamydia.

PMID- 22857142
TI  - The effect of mixing events on the dynamics of pH1N1 outbreaks at small
      residential colleges.
AB  - OBJECTIVE: The authors examine the dynamics and the impact of all-campus events
      on pH1N1 spread at Bates College in fall 2009, with comparisons to 3 other
      campuses. PARTICIPANTS: Students (N = 285) presented or called in to the Bates
      Health Center with symptoms consistent with influenza-like illness. METHODS:
      Health Center staff at Bates collected data on the outbreak; data from other
      colleges are from Web sites and journal articles. Data were analyzed using a
      mathematical model for influenza. RESULTS: Bates held 2 vaccine clinics mid
      outbreak. The data are consistent with the hypothesis that the vaccine clinics
      may have altered routine student interactions, facilitating transmission of pH1N1
      among students who otherwise might not have encountered each other. CONCLUSION:
      The vaccine clinics, held when vaccine became available, were too late to halt
      transmission. The disruptions to campus rhythms due to the vaccine clinics may
      instead have contributed to pH1N1 spread.

PMID- 22857143
TI  - Widespread disruptive selection in the wild is associated with intense resource
      competition.
AB  - BACKGROUND: Disruptive selection has been documented in a growing number of
      natural populations. Yet, its prevalence within individual systems remains
      unclear. Furthermore, few studies have sought to identify the ecological factors
      that promote disruptive selection in the wild. To address these issues, we
      surveyed 15 populations of Mexican spadefoot toad tadpoles, Spea multiplicata,
      and measured the prevalence of disruptive selection acting on resource-use
      phenotypes. We also evaluated the relationship between the strength of disruptive
      selection and the intensity of intraspecific competition-an ecological agent
      hypothesized to be an important driver of disruptive selection. RESULTS:
      Disruptive selection was the predominant mode of quadratic selection across all
      populations. However, a directional component of selection favoring an extreme
      ecomorph--a distinctive carnivore morph--was also common. Disruptive selection
      was strongest in populations experiencing the most intense intraspecific
      competition, whereas stabilizing selection was only found in populations
      experiencing relatively weak intraspecific competition. CONCLUSIONS: Disruptive
      selection can be common in natural populations. Intraspecific competition for
      resources may be a key driver of such selection.

PMID- 22857144
TI  - Overview of genetic defects in endocrinopathies in the island of Cyprus; evidence
      of a founder effect.
AB  - AIM: Hereditary endocrinopathies in Cyprus exhibit evidence of a founder effect
      and display the influence of past migration patterns. The genetic frequency and
      mutation pattern of a specific disorder of sex development (DSD), which is
      classified as 46,XX DSD or 46,XY DSD, and the non-classic form of congenital
      adrenal hyperplasia (NC-CAH) outline a type of genetic drift. RESULTS: Not only
      the high prevalence of the NC-CAH p.V281L mutation but also the rarity of CAH
      large lesions present a genetic diversity similar to that observed in the Middle
      Eastern countries. In addition, both the high frequency of the 5-alpha steroid
      reductase deficiency (5alphaSRD) IVS1-2A>G mutation and the carrier frequency of
      the 17-beta hydroxysteroid dehydrogenase 3 (17beta-HSD-3) p.R80Q mutation are
      good examples of a founder effect. p.R80Q can be considered a founder mutation,
      even though it has been identified in patients of Dutch, Brazilian, and
      Portuguese origin. This has led to the speculation that it has a Phoenician
      origin. Phoenicians as ancient traders migrated around 750 BC from present day
      Syria, Lebanon, and Israel toward Portugal, Spain, and also to nearby Cyprus.
      While the 5alphaSRD IVS1-2A>G mutation has already been extensively reported in
      Turkish patients, it is very common in the Eastern Mediterranean region.
      CONCLUSION: This short article portrays clearly, through specific endocrine
      genetic disorders, the past migration trends in Cyprus that shaped the present
      day gene pool of the Greek-Cypriot population.

PMID- 22857145
TI  - Metabolites: novel therapeutics or "me-too" drugs? Using desvenlafaxine as an
      example.

PMID- 22857146
TI  - Hydrogen donor-acceptor fluctuations from kinetic isotope effects: a
      phenomenological model.
AB  - Kinetic isotope effects (KIEs) and their temperature dependence can probe the
      structural and dynamic nature of enzyme-catalyzed proton or hydride transfers.
      The molecular interpretation of their temperature dependence requires expensive
      and specialized quantum mechanics/molecular mechanics (QM/MM) calculations to
      provide a quantitative molecular understanding. Currently available
      phenomenological models use a nonadiabatic assumption that is not appropriate for
      most hydride and proton-transfer reactions, while others require more parameters
      than the experimental data justify. Here we propose a phenomenological
      interpretation of KIEs based on a simple method to quantitatively link the size
      and temperature dependence of KIEs to a conformational distribution of the
      catalyzed reaction. This model assumes adiabatic hydrogen tunneling, and by
      fitting experimental KIE data, the model yields a population distribution for
      fluctuations of the distance between donor and acceptor atoms. Fits to data from
      a variety of proton and hydride transfers catalyzed by enzymes and their mutants,
      as well as nonenzymatic reactions, reveal that steeply temperature-dependent KIEs
      indicate the presence of at least two distinct conformational populations, each
      with different kinetic behaviors. We present the results of these calculations
      for several published cases and discuss how the predictions of the calculations
      might be experimentally tested. This analysis does not replace molecular QM/MM
      investigations, but it provides a fast and accessible way to quantitatively
      interpret KIEs in the context of a Marcus-like model.

PMID- 22857147
TI  - Simultaneous control of pH and ionic strength during interfacial rheology of beta
      lactoglobulin fibrils adsorbed at liquid/liquid Interfaces.
AB  - Proteins can aggregate as amyloid fibrils under denaturing and destabilizing
      conditions such as low pH (2) and high temperature (90  degrees C). Fibrils of
      beta-lactoglobulin are surface active and form adsorption layers at fluid-fluid
      interfaces. In this study, beta-lactoglobulin fibrils were adsorbed at the oil
      water interface at pH 2. A shear rheometer with a bicone geometry set up was
      modified to allow subphase exchange without disrupting the interface, enabling
      the investigation of rheological properties after adsorption of the fibrils, as a
      function of time, different pH, and ionic strength conditions. It is shown that
      an increase in pH (2 to 6) leads to an increase of both the interfacial storage
      and loss moduli. At the isoelectric point (pH 5-6) of beta-lactoglobulin fibrils,
      the maximum storage and loss moduli are reached. Beyond the isoelectric point, by
      further increasing the pH, a decrease in viscoelastic properties can be observed.
      Amplitude sweeps at different pH reveal a weak strain overshoot around the
      isoelectric point. With increasing ionic strength, the moduli increase without a
      strain overshoot. The method developed in this study allows in situ subphase
      exchange during interfacial rheological measurements and the investigation of
      interfacial ordering.

PMID- 22857148
TI  - Investigating the relationship between UMODL1 gene polymorphisms and high myopia:
      a case-control study in Chinese.
AB  - BACKGROUND: The UMODL1 gene was found to be associated with high myopia in
      Japanese. This study aimed to investigate this gene for association with high
      myopia in Chinese. METHODS: Two groups of unrelated Han Chinese from Hong Kong
      were recruited using the same criteria: Sample Set 1 comprising 356 controls
      (spherical equivalent, SE, within +/-1 diopter or D) and 356 cases (SE <= -8D),
      and Sample Set 2 comprising 394 controls and 526 cases. Fifty-nine tag single
      nucleotide polymorphisms (SNPs) were selected and genotyped for Sample Set 1.
      Four SNPs were followed up with Sample Set 2. Both single-marker and haplotype
      analyses were performed with cases defined by different SE thresholds. Secondary
      phenotypes were also analyzed for association with genotypes. RESULTS: Data
      filtering left 57 SNPs for analysis. Single-marker analysis did not reveal any
      significant differences between cases and controls in the initial study. However,
      haplotype GCT for markers rs220168-rs220170-rs11911271 showed marginal
      significance (empirical P = 0.076; SE <= -12D for cases), but could not be
      replicated in the follow-up study. In contrast, non-synonymous SNP rs3819142 was
      associated with high myopia (SE <= -10D) in the follow-up study, but could not be
      confirmed using Sample Set 1. The SNP rs2839471, positive in the original
      Japanese study, gave negative results in all our analyses. Exploratory analysis
      of secondary phenotypes indicated that allele C of rs220120 was associated with
      anterior chamber depth (adjusted P = 0.0460). CONCLUSIONS: Common UMODL1
      polymorphisms were unlikely to be important in the genetic susceptibility to high
      myopia in Han Chinese.

PMID- 22857149
TI  - Expedient synthesis of norbenzomorphan library via multicomponent assembly
      process coupled with ring-closing reactions.
AB  - A 124-member norbenzomorphan library has been prepared utilizing a novel
      multicomponent assembly process (MCAP) followed by a variety of ring-closing
      reactions to generate norbenzomorphan scaffolds that were readily derivatized via
      a series of aryl halide cross-coupling and nitrogen functionalization reactions.
      Biological screening has revealed some novel activities that have not been
      previously associated with this class of compounds. 

PMID- 22857150
TI  - Water-soluble molecular capsule for the complexation of cesium and thallium
      cations.
AB  - Binding properties of cesium and thallium cations by an enantiopure cryptophane
      derivative PP-1 have been investigated in water under basic conditions. The
      binding process has been evidenced using electronic circular dichroism (ECD), and
      binding constants of the Cs(+)@PP-1 and Tl(+)@PP-1 complexes have been determined
      from isothermal titration calorimetry (ITC) experiments in LiOH/H(2)O,
      NaOH/H(2)O, and KOH/H(2)O solutions. In addition, Tl(+)@PP-1 complex has been
      characterized for the first time by (205)Tl NMR spectroscopy. Cryptophane 1
      exhibits an exceptionally high affinity for thallium and cesium cations in a
      large range of experimental conditions (nature, concentration of the counterion,
      and temperature). For example, binding constants as high as 2.9 * 10(9) M(-1) and
      5.3 * 10(8) M(-1) have been measured by ITC at 298 K in NaOH/H(2)O (0.1 M)
      solution, for the Tl(+)@PP-1 and Cs(+)@PP-1 complexes, respectively. The high
      affinity of cryptophane 1 for Cs(+) and Tl(+) cations is preserved at higher
      LiOH, NaOH, and KOH concentrations and under extreme basic conditions, revealing
      the stability and the great selectivity of this supramolecular system toward
      Li(+), Na(+), and K(+) cations.

PMID- 22857151
TI  - Antioxidative effects of Alisma orientale extract in palmitate-induced cellular
      injury.
AB  - CONTEXT: Alisma orientale (Sam.) Juzepczuk (Alismataceae) is an indigenous
      medicinal herb that has been traditionally used for diuretic, hypolipidemic, anti
      inflammatory, and antidiabetic proposes in northern and eastern Asia. OBJECTIVE:
      This study examined the mechanisms underlying the cytoprotective effect of an
      aqueous extract of A. orientale (AEAO) against long-chain saturated fatty acid
      induced cellular injury. MATERIALS AND METHODS: HepG2 cells were treated with 0.5
      mM palmitate to generate a cellular model of nonalcoholic fatty liver disease
      (NAFLD). Using this cellular model, the cytoprotective effect of AEAO (100 ug/mL)
      against long-chain saturated fatty acid-induced cellular injury was evaluated by
      measuring the steatosis, ROS accumulation, and apoptosis. RESULTS: AEAO
      significantly attenuated palmitate-induced intracellular steatosis and cellular
      damage up to 54 and 33%, respectively. Palmitate-induced intracellular levels of
      reactive oxygen species (ROS) and reactive aldehydes were significantly reduced
      in the presence of AEAO to 40 and 75%, respectively, suggesting that oxidative
      stress plays a role in the palmitate-induced damage. AEAO inhibited the palmitate
      mediated activation of c-Jun NH(2)-terminal kinase (JNK), a kinase that is
      correlated with NAFLD. Inhibition of JNK by SP600125 or addition of AEAO
      significantly reduced palmitate-induced steatosis, ROS accumulation, and
      apoptosis, indicating that the protective effects of AEAO against palmitate
      induced cellular damage result from blocking ROS-activated JNK signaling.
      DISCUSSION AND CONCLUSION: The combined properties of AEAO in cellular steatosis
      and ROS production are beneficial for treating NAFLD, which includes complex
      metabolic changes, such that modulation of a single target is often not
      sufficient to achieve the desired therapeutic effect.

PMID- 22857152
TI  - Foot strike patterns and ground contact times during high-calibre middle-distance
      races.
AB  - The aims of this study were to examine ground contact characteristics, their
      relationship with race performance, and the time course of any changes in ground
      contact time during competitive 800 m and 1500 m races. Twenty-two seeded, single
      sex middle-distance races totalling 181 runners were filmed at a competitive
      athletics meeting. Races were filmed at 100 Hz. Ground contact time was recorded
      one step for each athlete, on each lap of their race. Forefoot and midfoot
      strikers had significantly shorter ground contact times than heel strikers.
      Forefoot and midfoot strikers had significantly faster average race speed than
      heel strikers. There were strong large correlations between ground contact time
      and average race speed for the women's events and men's 1500 m (r = -0.521 to 
      0.623; P < 0.05), whereas the men's 800 m displayed only a moderate relationship
      (r = -0.361; P = 0.002). For each event, ground contact time for the first lap
      was significantly shorter than for the last lap, which might reflect runners
      becoming fatigued.

PMID- 22857153
TI  - Cystic fibrosis: the role of the small airways.
AB  - Cystic fibrosis (CF) infants are born with normal airway anatomy, and dilatation
      of mucus glands in smaller airways has been described as the earliest
      histological changes in the lung of patients. This and other evidence has led to
      the concept that the small airways may be the region demonstrating initial
      pathology. Studies clarifying this have been challenged by the lack of a clear
      definition of what constitutes "small airways" and the difficulties to find
      accurate measures to quantify and track abnormalities in this region of the lung.
      Dynamic lung function test are not ideally suited to capture small airway
      abnormalities as the overall surface area of the small airways is about 40 times
      greater than that of central airways. Measures that are linked to airway size
      therefore often fail to capture abnormalities in a disease such as cystic
      fibrosis that is unevenly distributed throughout the lung. This review summarizes
      our current understanding of the role of small airways in disease development in
      cystic fibrosis patients and describes the spectrum of diagnostic tools available
      to diagnose and follow small airway disease and highlight the opportunities as
      well as challenges of targeting small airways via aerosol therapy in CF patients.

PMID- 22857154
TI  - Efficacy and toxicity of whole brain radiotherapy in patients with multiple
      cerebral metastases from malignant melanoma.
AB  - BACKGROUND: To retrospectively access outcome and toxicity of whole brain
      radiotherapy (WBRT) in patients with multiple brain metastases (BM) from
      malignant melanoma (MM). PATIENTS AND METHODS: Results of 87 patients (median age
      58 years; 35 female, 52 male) treated by WBRT for BM of MM between 2000 and 2011
      were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56) or 40
      Gy in 20 fractions (n = 31). All but 9 patients suffered from extra-cerebral
      metastases. Prior surgical resection of BM was performed in 18 patients, salvage
      stereotactic radiosurgery in 13 patients. RESULTS: Mean follow-up was 8 months
      (range, 0-57 months), the 6- and 12-months overall-(OS) survival rates were 29.2%
      and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up
      imaging 6 (11) patients showed a complete (partial) remission, while 11 (17)
      patients had stable disease (intra-cerebral tumor progression). In comparison of
      total dose, the group treated with 40 Gy in 20 fractions achieved a significant
      longer OS (p = 0.003, median 3.1 vs. 5.6 months). Furthermore, DS-GPA score (p <
      0.001) as well as RPA class (p < 0.001) influenced significantly on OS and
      patients had a significantly longer OS after surgical resection (p = 0.001,
      median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral
      metastases didn't significantly impact on OS (p = 0.21). CONCLUSION: Treatment of
      BM from MM with WBRT is tolerated well and some remissions of BM could be
      achieved. An advantage for higher treatment total doses was seen. However,
      outcome is non-satisfying, and further improvements in treatment of BM from MM
      are warranted.

PMID- 22857256
TI  - Reinforced wind turbine blades--an environmental life cycle evaluation.
AB  - A fiberglass composite reinforced with carbon nanofibers (CNF) at the resin-fiber
      interface is being developed for potential use in wind turbine blades. An energy
      and midpoint impact assessment was performed to gauge impacts of scaling
      production to blades 40 m and longer. Higher loadings force trade-offs in energy
      return on investment and midpoint impacts relative to the base case while
      remaining superior to thermoelectric power generation in these indicators. Energy
      intensive production of CNFs forces impacts disproportionate to mass
      contribution. The polymer nanocomposite increases a 2 MW plant's global warming
      potential nearly 100% per kWh electricity generated with 5% CNF by mass in the
      blades if no increase in electrical output is realized. The relative scale of
      impact must be compensated by systematic improvements whether by deployment in
      higher potential zones or by increased life span; the trade-offs are expected to
      be significantly lessened with CNF manufacturing maturity. Significant challenges
      are faced in evaluating emerging technologies including uncertainty in future
      scenarios and process scaling. Inventories available for raw materials and monte
      carlos analysis have been used to gain insight to impacts of this development.

PMID- 22857257
TI  - The innate immune protein Nod2 binds directly to MDP, a bacterial cell wall
      fragment.
AB  - Mammalian Nod2 is an intracellular protein that is implicated in the innate
      immune response to the bacterial cell wall and is associated with the development
      of Crohn's disease, Blau syndrome, and gastrointestinal cancers. Nod2 is required
      for an immune response to muramyl dipeptide (MDP), an immunostimulatory fragment
      of bacterial cell wall, but it is not known whether MDP binds directly to Nod2.
      We report the expression and purification of human Nod2 from insect cells. Using
      novel MDP self-assembled monolayers (SAMs), we provide the first biochemical
      evidence for a direct, high-affinity interaction between Nod2 and MDP.

PMID- 22857258
TI  - ATP driven clathrin dependent entry of carbon nanospheres prefer cells with
      glucose receptors.
AB  - BACKGROUND: Intrinsically fluorescent glucose derived carbon nanospheres (CSP)
      efficiently enter mammalian cells and also cross the blood brain barrier (BBB).
      However, the mechanistic details of CSP entry inside mammalian cells and its
      specificity are not known. RESULTS: In this report, the biochemical and cellular
      mechanism of CSP entry into the living cell have been investigated. By employing
      confocal imaging we show that CSP entry into the mammalian cells is an ATP
      dependent clathrin mediated endocytosis process. Zeta potential studies suggest
      that it has a strong preference for cells which possess high levels of glucose
      transporters such as the glial cells, thereby enabling it to target individual
      organs/tissues such as the brain with increased specificity. CONCLUSION: The
      endocytosis of Glucose derived CSP into mammalian cells is an ATP dependent
      process mediated by clathrin coated pits. CSPs utilize the surface functional
      groups to target cells containing glucose transporters on its membrane thereby
      implicating a potential application for specific targeting of the brain or cancer
      cells.

PMID- 22857260
TI  - Lipids and proteins in membranes: from in silico to in vivo.

PMID- 22857259
TI  - Characterization and optimization of ArtinM lectin expression in Escherichia
      coli.
AB  - BACKGROUND: ArtinM is a d-mannose-specific lectin from Artocarpus integrifolia
      seeds that induces neutrophil migration and activation, degranulation of mast
      cells, acceleration of wound healing, induction of interleukin-12 production by
      macrophages and dendritic cells, and protective T helper 1 immune response
      against Leishmania major, Leishmania amazonensis and Paracoccidioides
      brasiliensis infections. Considering the important biological properties of
      ArtinM and its therapeutic applicability, this study was designed to produce high
      level expression of active recombinant ArtinM (rArtinM) in Escherichia coli
      system. RESULTS: The ArtinM coding region was inserted in pET29a(+) vector and
      expressed in E. coli BL21(DE3)-Codon Plus-RP. The conditions for overexpression
      of soluble ArtinM were optimized testing different parameters: temperatures (20,
      25, 30 or 37 degrees C) and shaking speeds (130, 200 or 220 rpm) during
      induction, concentrations of the induction agent IPTG (0.01-4 mM) and periods of
      induction (1-19 h). BL21-CodonPlus(DE3)-RP cells induced under the optimized
      conditions (incubation at 20 degrees C, at a shaking speed of 130 rpm, induction
      with 0.4 mM IPTG for 19 h) resulted in the accumulation of large amounts of
      soluble rArtinM. The culture provided 22.4 mg/L of rArtinM, which activity was
      determined by its one-step purification through affinity chromatography on
      immobilized d-mannose and glycoarray analysis. Gel filtration showed that rArtinM
      is monomeric, contrasting with the tetrameric form of the plant native protein
      (jArtinM). The analysis of intact rArtinM by mass spectrometry revealed a
      16,099.5 Da molecular mass, and the peptide mass fingerprint and esi-cid-ms/ms of
      amino acid sequences of peptides from a tryptic digest covered 41% of the total
      ArtinM amino acid sequence. In addition, circular dichroism and fluorescence
      spectroscopy of rArtinM indicated that its global fold comprises beta-sheet
      structure. CONCLUSIONS: Overall, the optimized process to express rArtinM in E.
      coli provided high amounts of soluble, correctly folded and active recombinant
      protein, compatible with large scale production of the lectin.

PMID- 22857261
TI  - Vitamin D intake and serum vitamin D in ethnically diverse urban schoolchildren.
AB  - OBJECTIVE: Low serum vitamin D, which largely affects ethnic minorities, is
      associated with obesity and other chronic diseases. Little is known about
      racial/ethnic differences in intake, particularly in children, or if any
      differences are associated with differences in serum 25-hydroxyvitamin D
      (25(OH)D). The objective of the present study was to determine whether
      racial/ethnic differences in dietary vitamin D intake exist and whether they
      explain differences in 25(OH)D. DESIGN: Vitamin D intakes (Block Kids 2004 FFQ)
      and 25(OH)D were measured. Race/ethnicity was parent-reported (white (37.9 %),
      Hispanic (32.4 %), black (8.3 %), Asian (10.3 %), multi-racial/other (11.0 %)).
      Multivariable analyses were conducted to examine the associations among dietary
      vitamin D and race/ethnicity, as well as 25(OH)D, independent of BMI Z-score and
      other covariates. SETTING: Elementary/middle schools in Somerville, MA, USA,
      during January-April 2010. SUBJECTS: Schoolchildren (n 145) in 4th-8th grade.
      RESULTS: Only 2.1 % met the 2011 RDA (15 MUg/d (600 IU/d)). Average dietary
      intake was 3.5 (sd 2.2) MUg/d (140 (sd 89.0) IU/d). No racial/ethnic differences
      in intake were evident. Most (83.4 %) were 25(OH)D deficient (<20 ng/ml; 16.0 (sd
      6.5) ng/ml). In ANOVA post hoc analyses, 25(OH)D levels were lower in Hispanics
      than whites (14.6 (sd 6.1) ng/ml v. 17.9 (sd 4.6) ng/ml; P < 0.01). Dietary
      vitamin D was associated with 25(OH)D overall (P < 0.05), but did not explain the
      racial/ethnic differences in 25(OH)D. CONCLUSIONS: Most children in this north
      east US sample did not meet dietary recommendations for vitamin D and were
      vitamin D deficient. Dietary vitamin D did not explain the difference in 25(OH)D
      between Hispanic and white children. Further research is needed to determine if
      changes in dietary vitamin D by race/ethnicity can impact 25(OH)D levels.

PMID- 22857262
TI  - A toll-like receptor 3 ligand enhances protective effects of vaccination against
      Marek's disease virus and hinders tumor development in chickens.
AB  - Marek's disease (MD) is caused by Marek's disease virus (MDV). Various vaccines
      including herpesvirus of turkeys (HVT) have been used to control this disease.
      However, HVT is not able to completely protect against very virulent strains of
      MDV. The objective of this study was to determine whether a vaccination protocol
      consisting of HVT and a Toll-like receptor (TLR) ligand could enhance protective
      efficacy of vaccination against MD. Hence, chickens were immunized with HVT and
      subsequently treated with synthetic double-stranded RNA polyriboinosinic
      polyribocytidylic [poly(I:C)], a TLR3 ligand, before or after being infected with
      a very virulent strain of MDV. Among the groups that were HVT-vaccinated and
      challenged with MDV, the lowest incidence of tumors was observed in the group
      that received poly(I:C) before and after MDV infection. Moreover, the groups that
      received a single poly(I:C) treatment either before or after MDV infection were
      better protected against MD tumors compared to the group that only received HVT.
      No association was observed between viral load, as determined by MDV genome copy
      number, and the reduction in tumor formation. Overall, the results presented here
      indicate that poly(I:C) treatment, especially when it is administered prior to
      and after HVT vaccination, enhances the efficacy of HVT vaccine and improves
      protection against MDV.

PMID- 22857263
TI  - Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in
      Leishmania.
AB  - Leishmania are unicellular eukaryotes that have many markedly original molecular
      features compared with other uni- or multicellular eukaryotes like yeasts or
      mammals. Genome plasticity in this parasite has been the subject of many
      publications, and has been associated with drug resistance or adaptability.
      Aneuploidy has been suspected by several authors and it is now confirmed using
      state-of-the-art technologies such as high-throughput DNA sequencing. The
      analysis of genome contents at the single cell level using fluorescence in situ
      hybridization (FISH) has brought a new light on the genome organization: within a
      cell population, every chromosome, in every cell, may be present in at least two
      ploidy states (being either monosomic, disomic or trisomic), and the chromosomal
      content varies greatly from cell to cell, thus generating a constitutive intra
      strain genomic heterogeneity, here termed 'mosaic aneuploidy'. Mosaic aneuploidy
      deeply affects the genetics of these organisms, leading, for example, to an
      extreme degree of intra-strain genomic diversity, as well as to a clearance of
      heterozygous cells in the population without however affecting genetic
      heterogeneity. Second, mosaic aneuploidy might be considered as a powerful
      strategy evolved by the parasite for adapting to modifications of environment
      conditions as well as for the emergence of drug resistance. On the whole, mosaic
      aneuploidy may be considered as a novel mechanism for generating phenotypic
      diversity driven by genomic plasticity.

PMID- 22857265
TI  - Combined excision and intralesional bevacizumab for sebaceous carcinoma of the
      eyelid in an Amur tiger (Panthera tigris altaica).
AB  - An 18-year-old zoo-kept female Amur tiger presented with an approximately 5 mm
      diameter lateral canthal eyelid mass in the left eye which grossly appeared red
      and irregular. The mass was completely excised via lateral canthoplasty.
      Histopathologic evaluation was consistent with a diagnosis of sebaceous cell
      carcinoma, which is a potentially aggressive cutaneous neoplasm. The sebaceous
      carcinoma recurred within 3 months and slowly increased in size until a second
      surgical excision was performed 9 months following the first surgery. The second
      surgical excision was combined with intralesional injection of 10 mg of the
      antiangiogenic drug bevacizumab. Histology confirmed the diagnosis. The tiger was
      euthanized 16 months postoperatively for reasons unrelated to, and without
      recurrence of, the eyelid neoplasm. At postmortem, no gross periocular or
      metastatic lesions were noted, and histopathology of the lateral canthus provided
      no evidence of recurrence. Surgical excision combined with intralesional
      bevacizumab treatment induced life-long resolution of the sebaceous carcinoma.
      Bevacizumab treatment may be associated with the regression of periocular
      angiogenic proliferative conditions, including neoplasia, by inhibiting
      angiogenesis.

PMID- 22857264
TI  - Copy number expansion of the STX17 duplication in melanoma tissue from Grey
      horses.
AB  - BACKGROUND: Greying with age in horses is an autosomal dominant trait, associated
      with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We
      recently identified a 4.6 kb duplication in STX17 to be associated with the
      phenotype. The aims of this study were to investigate if the duplication in Grey
      horses shows copy number variation and to exclude that any other polymorphism is
      uniquely associated with the Grey mutation. RESULTS: We found little evidence for
      copy number expansion of the duplicated sequence in blood DNA from Grey horses.
      In contrast, clear evidence for copy number expansions was indicated in five out
      of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher
      copy number in aggressive tumours was also found. Massively parallel resequencing
      of the ~350 kb Grey haplotype did not reveal any additional mutations perfectly
      associated with the phenotype, confirming the duplication as the true causative
      mutation. We identified three SNP alleles that were present in a subset of Grey
      haplotypes within the 350 kb region that shows complete linkage disequilibrium
      with the causative mutation. Thus, these three nucleotide substitutions must have
      occurred subsequent to the duplication, consistent with our interpretation that
      the Grey mutation arose more than 2,000 years before present. CONCLUSIONS: These
      results suggest that the mutation acts as a melanoma-driving regulatory element.
      The elucidation of the mechanistic features of the duplication will be of
      considerable interest for the characterization of these horse melanomas as well
      as for the field of human melanoma research.

PMID- 22857266
TI  - Prospects and challenges of reprogrammed cells in hematology and oncology.
AB  - Induced pluripotent stem cells (iPSCs) have emerged as a promising basis for
      modeling pediatric genetic disorders, allowing the derivation, study, and genetic
      correction of disease and patient-specific cell lines in vitro. Similar to
      embryonic stem cells (ESCs), iPSCs are capable of unlimited in vitro expansion
      and derivation of many cell types, including hematopoietic stem cells (HSCs).
      These may not only allow large scale screenings to develop therapeutic compounds,
      but also help to overcome cross-species barriers of genetically engineered animal
      models, which do not adequately recapitulate the associated human phenotype.
      Here, we review the current state and emerging developments of iPSC research,
      which can be exploited as a tool in modeling pediatric hematopoietic disorders
      and could lead to new clinical applications in gene and cell therapies.

PMID- 22857267
TI  - MicrobesFlux: a web platform for drafting metabolic models from the KEGG
      database.
AB  - BACKGROUND: Concurrent with the efforts currently underway in mapping microbial
      genomes using high-throughput sequencing methods, systems biologists are building
      metabolic models to characterize and predict cell metabolisms. One of the key
      steps in building a metabolic model is using multiple databases to collect and
      assemble essential information about genome-annotations and the architecture of
      the metabolic network for a specific organism. To speed up metabolic model
      development for a large number of microorganisms, we need a user-friendly
      platform to construct metabolic networks and to perform constraint-based flux
      balance analysis based on genome databases and experimental results. RESULTS: We
      have developed a semi-automatic, web-based platform (MicrobesFlux) for generating
      and reconstructing metabolic models for annotated microorganisms. MicrobesFlux is
      able to automatically download the metabolic network (including enzymatic
      reactions and metabolites) of ~1,200 species from the KEGG database (Kyoto
      Encyclopedia of Genes and Genomes) and then convert it to a metabolic model
      draft. The platform also provides diverse customized tools, such as gene
      knockouts and the introduction of heterologous pathways, for users to reconstruct
      the model network. The reconstructed metabolic network can be formulated to a
      constraint-based flux model to predict and analyze the carbon fluxes in microbial
      metabolisms. The simulation results can be exported in the SBML format (The
      Systems Biology Markup Language). Furthermore, we also demonstrated the platform
      functionalities by developing an FBA model (including 229 reactions) for a recent
      annotated bioethanol producer, Thermoanaerobacter sp. strain X514, to predict its
      biomass growth and ethanol production. CONCLUSION: MicrobesFlux is an
      installation-free and open-source platform that enables biologists without prior
      programming knowledge to develop metabolic models for annotated microorganisms in
      the KEGG database. Our system facilitates users to reconstruct metabolic networks
      of organisms based on experimental information. Through human-computer
      interaction, MicrobesFlux provides users with reasonable predictions of microbial
      metabolism via flux balance analysis. This prototype platform can be a
      springboard for advanced and broad-scope modeling of complex biological systems
      by integrating other "omics" data or 13 C- metabolic flux analysis results.
      MicrobesFlux is available at
      http://tanglab.engineering.wustl.edu/static/MicrobesFlux.html and will be
      continuously improved based on feedback from users.

PMID- 22857268
TI  - GnRH-agonist ovulation trigger in patients undergoing controlled ovarian
      hyperstimulation for IVF with ultrashort flare GnRH-agonist combined with
      multidose GnRH-antagonist protocol.
AB  - OBJECTIVE: To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH
      agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH
      antagonist (GnRH-ant) protocol is as effective as in patients at high risk to
      develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the
      multidose GnRH-ant protocol. DESIGN: Cohort study. SETTING: University hospital.
      PATIENTS: All consecutive women aged <=35 years admitted to our IVF unit from
      January 2011 to October 2011 who reached the ovum pick-up stage. INTERVENTIONS:
      Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder
      patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH
      antagonist controlled ovarian hyperstimulation (COH) protocols. MAIN OUTCOME
      MEASURES: Ovarian stimulation characteristics, percentage of mature oocytes,
      fertilization and pregnancy rates. RESULTS: No inbetween groups differences were
      observed in ovarian-stimulation related variable, percentage of mature oocytes,
      fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in
      the study, or the control groups. CONCLUSIONS: Three consecutive doses of daily
      GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH
      protocol, did not interfere with the ability of the GnRH-ag to trigger final
      oocytes maturation at the end of the COH cycle.

PMID- 22857269
TI  - Dominant optic atrophy in Denmark - report of 15 novel mutations in OPA1, using a
      strategy with a detection rate of 90%.
AB  - BACKGROUND: Investigation of the OPA1 mutation spectrum in autosomal dominant
      optic atrophy (ADOA) in Denmark. METHODS: Index patients from 93 unrelated ADOA
      families were assessed for a common Danish founder mutation
      (c.2826_2836delinsGGATGCTCCA) inOPA1. If negative, direct DNA sequencing of the
      coding sequence and multiplex ligation-dependent probe amplification (MLPA) were
      performed. Results from MLPA analysis have been previously reported. Haplotype
      analysis was carried out analysing single nucleotide polymorphisms (SNP).
      Retrospective clinical data were retrieved from medical files. RESULTS: Probably
      causative mutations were identified in 84 out of 93 families (90%) including 15
      novel mutations. Three mutations c.983A > G, c.2708_2711delTTAG and
      c.2826_2836delinsGGATGCTCCA, were responsible for ADOA in10, 11 and 28 families,
      respectively, corresponding to 11%, 12% and 30%. A common haplotype in nine of
      ten c.983A > G families suggests that they descend from a single founder. The
      c.2708_2711delTTAG mutation was present on at least two haplotypes and has been
      repeatedly reported in various ethnic groups,thus represents a mutational
      hotspot. Clinical examinations of index patients with the two latter mutations
      demonstrated large inter- and intra-familial variations apparently. CONCLUSIONS:
      Genetic testing for OPA1mutations assist in the diagnosis. We have identified
      mutations in OPA1 in 90% of families including 15 novel mutations. Both DNA
      sequencing and MLPA analysis are necessary to achieve a high detection rate. More
      than half of the affected families in Denmark are represented by three common
      mutations, at least two of which are due to a founder effect, which may account
      for the high prevalence of ADOA in Denmark.

PMID- 22857270
TI  - Adapting the Abbreviated Impactor Measurement (AIM) concept to make appropriate
      inhaler aerosol measurements to compare with clinical data: a scoping study with
      the "Alberta" idealized throat (AIT) inlet.
AB  - BACKGROUND: The Abbreviated Impactor Measurement (AIM) concept simplifies
      determination of aerodynamic size metrics for inhaler quality control testing. A
      similar approach is needed to compare in vitro particle size distribution metrics
      with human respiratory tract (HRT) deposition. METHODS: An abbreviated impactor
      based on the Andersen eight-stage cascade impactor (ACI) was developed having two
      size-fractionating stages with cut-points at 4.7 and 1.1 MUm aerodynamic diameter
      at 28.3 L/min, to distinguish between coarse (CPM), fine (FPM), and extra-fine
      (EPM) mass fractions likely to deposit in the oropharynx, airways of the lungs,
      or be exhaled, respectively. In vitro data were determined for pressurized
      metered dose inhaler (pMDI)-delivered salbutamol (100 MUg/actuation ex valve)
      with an "Alberta" idealized adult upper airway (throat) inlet (AIM-pHRT).
      Corresponding benchmark data for a full resolution Andersen eight-stage cascade
      impactor with "Alberta" idealized throat (ACI-AIT) and ACI-Ph.Eur./USP inlet were
      obtained with the same product. RESULTS: Mass recoveries (MUg/actuation; mean +/-
      SD) were equivalent at 100.5 +/- 0.7; 97.2 +/- 4.9 and 101.5 +/- 9.5 for the AIM
      pHRT, ACI-AIT, and ACI-Ph.Eur./USP induction port, respectively [one-way analysis
      of variance (ANOVA), p=0.64]. Corresponding values of CPM were 59.2 +/- 4.2; 58.4
      +/- 2.4, and 65.6 +/- 5.8; the AIT captured larger particles more efficiently
      than the Ph.Eur./USP induction port, so that less large particle mass was
      apparent in the upper stages of the ACI-AIT (p <= 0.037). Equivalent values of
      FPM were similar regardless of inlet/abbreviation at 41.3 +/- 4.2; 38.7 +/- 3.0,
      and 35.9 +/- 3.8 (p=0.054), and EPM measures (1.7 +/- 0.3; 2.0 +/- 0.5; 2.1 +/-
      0.3) were also comparable (p=0.32). CONCLUSIONS: The AIT inlet significantly
      increased the capture of the coarse fraction compared with that collected by the
      Ph.Eur./USP induction port. Measures obtained using the AIM-pHRT apparatus were
      comparable with those obtained with the ACI-AIT.

PMID- 22857271
TI  - Regulatory aspects of Phase 3 endpoints for new inhaled antibiotics for cystic
      fibrosis patients with chronic Pseudomonas aeruginosa infections.
AB  - Available regulatory guidelines for developing inhaled anti-infective therapies
      offer general advice, but specific guidance often provides conflicting and
      outdated advice in regard to clinical trial design. For instance, the
      availability of two approved drugs makes the conduct of placebo-controlled trials
      longer than 28 days problematic. Comparator drugs require use per the product
      label, making comparator trials difficult to blind as taste, foaming, regimen,
      device, and delivery time differences are present. Currently, there is no
      consensus on the most appropriate endpoints for evaluation of aerosolized
      antimicrobials. FEV(1) is a surrogate endpoint that it is a predictor of
      mortality--it is standardized, reproducible, noninvasive, simple, and inexpensive
      to perform but small statistically significant changes may not be clinically
      important. FEV(1) improvement also has a ceiling effect in patients with mild
      lung function impairment and spirometry cannot be reliably done in patients under
      the age of 6 years. A patient-reported outcome is a promising clinical endpoint.
      However, there is not currently an accepted tool that can be used as a primary
      endpoint for the FDA or the EMA, although the latter recognizes the CFQ-R as a
      validated secondary endpoint and the FDA grandfathered acceptance of the CFQ-R
      respiratory domain in the pivotal aztreonam for inhalation study. Exacerbations
      are an important clinical endpoint that reflects morbidity and are a major driver
      of cost of care, but they occur infrequently and a standardized definition has
      not been reached. Furthermore, an exacerbation endpoint may fail even with an
      otherwise effective antibiotic therapy. Regulatory authorities will have a
      difficult time approving any new inhaled antibiotic based on one clinical
      endpoint alone.

PMID- 22857272
TI  - Comparison of ISO standards for device performance; 20072 and 27427: a critical
      appraisal.
AB  - Two separate international standards, ISO 20072:2009 and ISO 27427:2010, have
      recently been published that relate to the development and performance testing of
      oral inhaled products (OIPs). The scope of ISO 20072 encompasses all OIP forms
      except nebulizing systems, whereas ISO 27427 was developed specifically for this
      class of OIP. Compliance with these standards will likely be necessary for
      manufacturers seeking approval to market inhaler devices in the European Union
      (EU). Their adoption in the United States may take a considerable time, but the
      FDA has expressed support in general terms for the ISO process. Key aspects of
      both standards that are very different in style and content are identified and
      discussed from the perspective of a potential user. In the approach adopted by
      ISO 20072, a formalized risk assessment is undertaken as a key part of design
      verification, in order to develop the Device Functionality Profile (DFP) of the
      device. The DFP is subsequently verified by the System Verification Test (SVT),
      in which pharmacopeial test methods are used to evaluate in vitro performance of
      the device with a chosen drug product in a statistically robust manner. On the
      other hand, ISO 27427 adopts a more prescriptive approach that involves
      performance verification of the finished nebulizing system using 1% w/v
      salbutamol as the test formulation. Although ISO 27427 is currently undergoing
      revision, at present it is unclear whether the changes that are made will
      significantly alter its fundamentally different approach to device performance
      verification. A strong case can be made for a single OIP-wide ISO standard, based
      on the principles developed in ISO 20072 and that makes use of the well
      understood and validated in vitro test procedures that are available or will
      shortly be available in the case of nebulizing systems, in the United States and
      European pharmacopeias.

PMID- 22857273
TI  - Clinically relevant test methods to establish in vitro equivalence for spacers
      and valved holding chambers used with pressurized metered dose inhalers (pMDIs).
AB  - Regulatory guidance in Canada and Europe recommends that the manufacturer of an
      inhaled drug product delivered by pressurized metered-dose inhaler (pMDI)
      identify a spacer (S) or valved holding chamber (VHC) to be used with their
      designated product. It therefore becomes necessary to include the S/VHC in the
      process of establishing bioequivalence (BE) to the reference pMDI product for
      both new-entry generic and subsequent market entry products (SMEPs). S/VHCs
      substantially modify the aerodynamic particle size distribution (APSD) of the
      inhaled medication, and potentially the spatial distribution of the mass of
      active pharmaceutical ingredient(s) [API(s)] depositing in the respiratory tract.
      The processes whereby S/VHCs can influence BE outcomes are examined, and the
      inadequacy of compendial in vitro methods to provide pertinent information to
      assess BE for the pMDI+VHC combination is highlighted. A three-part strategy is
      proposed whereby in vitro testing for BE can simulate more clinically-relevant
      conditions than in the current compendial procedures: 1. The inclusion of a short
      delay between inhaler actuation and sampling onset is appropriate when
      determining APSD at flow rate(s) suitable for the intended patient population; 2.
      Assessment of total emitted mass ex S/VHC by simulating tidal breathing
      pattern(s) appropriate for intended use; 3. Incorporation of appropriate face
      model(s), representative of the intended patient age range(s), into test
      procedures for S/VHCs with facemask, enabling clinically-appropriate dead space
      and fit-to-face to be simulated. Although the compendial authorities have been
      slow to recognize the need for such in vitro testing, a Canadian standard
      provides direction for implementing most proposals, which should result in better
      performance predictions and more appropriate clinical outcomes, highlighting
      similarities and differences between reference and test products.

PMID- 22857274
TI  - The US and EU regulatory landscapes for locally acting generic/hybrid inhalation
      products intended for treatment of asthma and COPD.
AB  - This is a review of the current regulatory requirements associated with
      development and submission of abridged dossiers for locally acting inhalation
      drugs intended for the treatment of asthma and chronic obstructive pulmonary
      disease. The current EU law does not provide for submission of such products as
      generics due to the definition of bioequivalence and bioavailability; instead
      they must be submitted as hybrids. A guideline from 2009 is available that
      suggests a stepwise approach toward approval. An applicant should first consider
      the degree of in vitro match with the reference product; provided that the match
      is extensive, approval may be granted. If the in vitro match cannot be proven,
      the next step is comparison of lung deposition and systemic exposure. If this
      match is proven, approval may be granted; otherwise, the final step is
      pharmacodynamic evaluation. In the United States, submission as a generic is
      possible, but only a single specific guidance document from 1989 is in force. It
      describes in vitro requirements for comparison of albuterol and metaproterenol
      pressurized metered dose inhalers. Applicants are encouraged to seek dialogue
      with regulators prior to and during development. Although parallel scientific
      advice procedures have been established between the US Food and Drug
      Administration and the European Medicines Agency, the two authorities give
      independent and individual advice.

PMID- 22857379
TI  - Visual color perception in green exercise: positive effects on mood and perceived
      exertion.
AB  - Positive effects of green exercise on physical and psychological wellbeing have
      been found, yet little is known about the underlying cognitive mechanisms
      responsible for such effects. The purpose of this visual sensation study was to
      establish the extent to which the color green, as a primitive visual feature of
      many natural environments, contributes to the green exercise effect. Fourteen
      participants performed three moderate-intensity 5-min cycling tasks (50% peak
      power output) while watching video footage of a rural cycling course that
      simulated cycling through a real natural environment. The three randomly counter
      balanced video conditions were unedited (V(GREEN)), achromatic (V(GRAY)) or red
      filter (V(RED)). Lower total mood disturbance and ratings of perceived exertion
      were found during the V(GREEN) compared to V(GRAY) and V(RED). Feelings of anger
      were higher after V(RED) compared to the other conditions. Feelings of tension,
      depression, fatigue, vigor, and confusion did not differ among conditions. This
      is the first study to show that the color green, as a primitive feature of visual
      sensation, has a contributory effect toward positive green exercise outcomes.

PMID- 22857380
TI  - Force field development for actinyl ions via quantum mechanical calculations: an
      approach to account for many body solvation effects.
AB  - Advances in computational algorithms and methodologies make it possible to use
      highly accurate quantum mechanical calculations to develop force fields (pair
      wise additive intermolecular potentials) for condensed phase simulations. Despite
      these advances, this approach faces numerous hurdles for the case of actinyl
      ions, AcO2(n+) (high-oxidation-state actinide dioxo cations), mainly due to the
      complex electronic structure resulting from an interplay of s, p, d, and f
      valence orbitals. Traditional methods use a pair of molecules ("dimer") to
      generate a potential energy surface (PES) for force field parametrization based
      on the assumption that many body polarization effects are negligible. We show
      that this is a poor approximation for aqueous phase uranyl ions and present an
      alternative approach for the development of actinyl ion force fields that
      includes important many body solvation effects. Force fields are developed for
      the UO2(2+) ion with the SPC/Fw, TIP3P, TIP4P, and TIP5P water models and are
      validated by carrying out detailed molecular simulations on the uranyl aqua ion,
      one of the most characterized actinide systems. It is shown that the force fields
      faithfully reproduce available experimental structural data and hydration free
      energies. Failure to account for solvation effects when generating PES leads to
      overbinding between UO2(2+) and water, resulting in incorrect hydration free
      energies and coordination numbers. A detailed analysis of arrangement of water
      molecules in the first and second solvation shell of UO2(2+) is presented. The
      use of a simple functional form involving the sum of Lennard-Jones + Coulomb
      potentials makes the new force field compatible with a large number of available
      molecular simulation engines and common force fields.

PMID- 22857381
TI  - Enlightenment and measurement - a way to improve health among high school
      students.
AB  - This paper examines the effect of participating in a web-based health programme
      that promotes personal tracking of high school students' own measurements of a
      number of health-related parameters. Danish cross-sectional survey data were used
      to examine the effects of the health programme on various health measures. Both
      quantile regression models and standard ordinary least squares (OLS) models were
      used to explore the correlations between the students' participation in the
      health programme and their body mass index (BMI), body fat percentage, aerobic
      fitness, and well-being. Participation in the health programme increased BMI and
      aerobic fitness among students with a BMI or an aerobic fitness value ranging
      from the 25th percentile to the 75th percentile and reduced body fat percentage
      among students with the highest percentages of body fat. In addition, the health
      programme led to an increased feeling of wellbeing among students, especially
      those with high BMI levels and poor aerobic fitness. As the schools participated
      in the health programme on voluntary basis and at a financial cost to themselves,
      the positive effects of participation found can only be stated to be valid among
      students from committed schools.

PMID- 22857383
TI  - Proteomic analysis of plasma membranes isolated from undifferentiated and
      differentiated HepaRG cells.
AB  - Liver infection with hepatitis B virus (HBV), a DNA virus of the Hepadnaviridae
      family, leads to severe disease, such as fibrosis, cirrhosis and hepatocellular
      carcinoma. The early steps of the viral life cycle are largely obscure and the
      host cell plasma membrane receptors are not known. HepaRG is the only
      proliferating cell line supporting HBV infection in vitro, following specific
      differentiation, allowing for investigation of new host host-cell factors
      involved in viral entry, within a more robust and reproducible environment. Viral
      infection generally begins with receptor recognition at the host cell surface,
      following highly specific cell-virus interactions. Most of these interactions are
      expected to take place at the plasma membrane of the HepaRG cells. In the present
      study, we used this cell line to explore changes between the plasma membrane of
      undifferentiated (-) and differentiated (+) cells and to identify differentially
      regulated proteins or signaling networks that might potentially be involved in
      HBV entry. Our initial study identified a series of proteins that are
      differentially expressed in the plasma membrane of (-) and (+) cells and are good
      candidates for potential cell-virus interactions. To our knowledge, this is the
      first study using functional proteomics to study plasma membrane proteins from
      HepaRG cells, providing a platform for future experiments that will allow us to
      understand the cell-virus interaction and mechanism of HBV viral infection.

PMID- 22857382
TI  - Development of an efficient, non-viral transfection method for studying gene
      function and bone growth in human primary cranial suture mesenchymal cells
      reveals that the cells respond to BMP2 and BMP3.
AB  - BACKGROUND: Achieving efficient introduction of plasmid DNA into primary cultures
      of mammalian cells is a common problem in biomedical research. Human primary
      cranial suture cells are derived from the connective mesenchymal tissue between
      the bone forming regions at the edges of the calvarial plates of the skull.
      Typically they are referred to as suture mesenchymal cells and are a
      heterogeneous population responsible for driving the rapid skull growth that
      occurs in utero and postnatally. To better understand the molecular mechanisms
      involved in skull growth, and in abnormal growth conditions, such as
      craniosynostosis, caused by premature bony fusion, it is essential to be able to
      easily introduce genes into primary bone forming cells to study their function.
      RESULTS: A comparison of several lipid-based techniques with two electroporation
      based techniques demonstrated that the electroporation method known as
      nucleofection produced the best transfection efficiency. The parameters of
      nucleofection, including cell number, amount of DNA and nucleofection program,
      were optimized for transfection efficiency and cell survival. Two different genes
      and two promoter reporter vectors were used to validate the nucleofection method
      and the responses of human primary suture mesenchymal cells by fluorescence
      microscopy, RT-PCR and the dual luciferase assay. Quantification of bone
      morphogenetic protein (BMP) signalling using luciferase reporters demonstrated
      robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic
      BMP3. CONCLUSIONS: A nucleofection protocol has been developed that provides a
      simple and efficient, non-viral alternative method for in vitro studies of gene
      and protein function in human skull growth. Human primary suture mesenchymal
      cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a
      valuable method for studying the potential competing action of these two bone
      growth factors in a model system of cranial bone growth.

PMID- 22857384
TI  - Clinical significance of TSH circadian variability in patients with
      hypothyroidism.
AB  - OBJECTIVE: To investigate the clinical significance of thyroid-stimulating
      hormone (TSH) circadian variability in patients with hypothyroidism. DESIGN: A
      total of 20 women with subclinical hypothyroidism and 22 patients taking L
      thyroxine replacement therapy for hypothyroidism were enrolled in the study.
      Measurements of serum TSH levels were done twice a day from 08.00 to 09.00 a.m.
      and from 2.00 to 4.00 p.m. RESULTS: The morning median TSH value in the patients
      with subclinical hypothyroidism was 5.83 mU/L; in the afternoon, it was 3.79
      mU/L. The range of TSH circadian variability reached the level of 73%. According
      to the current TSH reference interval, hypothyroidism was not diagnosed in about
      50% of the cases in the afternoon. The morning median TSH value in the patients
      taking l-thyroxine was 3.27 mU/L; it decreased to the value of 2.18 mU/L in the
      afternoon. The range of TSH circadian variability reached the level of 64.7%.
      Further analysis demonstrated inadequate compensation of hypothyroidism, which
      was defined in 45.5% of the morning samples and in 9% of the afternoon samples (p
      < 0.05). CONCLUSION: The time of blood sampling has an important role in the
      interpretation of TSH levels. Moreover, the high TSH circadian variability should
      be considered in discussions about the narrowing of its reference range.

PMID- 22857385
TI  - The root-knot nematode calreticulin Mi-CRT is a key effector in plant defense
      suppression.
AB  - Root-knot nematodes (RKN) are obligate biotrophic parasites that settle close to
      the vascular tissues in roots, where they induce the differentiation of
      specialized feeding cells and maintain a compatible interaction for 3 to 8 weeks.
      Transcriptome analyses of the plant response to parasitic infection have shown
      that plant defenses are strictly controlled during the interaction. This suggests
      that, similar to other pathogens, RKN secrete effectors that suppress host
      defenses. We show here that Mi-CRT, a calreticulin (CRT) secreted by the nematode
      into the apoplasm of infected tissues, plays an important role in infection
      success, because Mi-CRT knockdown by RNA interference affected the ability of the
      nematodes to infect plants. Stably transformed Arabidopsis thaliana plants
      producing the secreted form of Mi-CRT were more susceptible to nematode infection
      than wild-type plants. They were also more susceptible to infection with another
      root pathogen, the oomycete Phytophthora parasitica. Mi-CRT overexpression in A.
      thaliana suppressed the induction of defense marker genes and callose deposition
      after treatment with the pathogen-associated molecular pattern elf18. Our results
      show that Mi-CRT secreted in the apoplasm by the nematode has a role in the
      suppression of plant basal defenses during the interaction.

PMID- 22857386
TI  - The impact of adding front-of-package sodium content labels to grocery products:
      an experimental study.
AB  - OBJECTIVE: Canadians consume approximately twice the daily Adequate Intake of
      sodium. The present study examined the efficacy of four types of front-of-package
      (FOP) sodium labels at influencing consumers' selection of products low v. high
      in sodium. DESIGN: Participants were randomly assigned to one of five
      experimental conditions: (i) control condition with no FOP label; (ii) basic
      numeric FOP label; (iii) numeric FOP label with 'high' and 'low' sodium content
      descriptors; (iv) detailed Traffic Light (TL) label with colour coding, content
      descriptors and numeric information; and (v) simple TL label with no numeric
      information. Participants were shown pairs of grocery products that varied in
      sodium content and told they could choose a free sample. Selection of the low
      sodium v. the high-sodium product was the primary behavioural outcome, in
      addition to ratings of effectiveness, understanding, liking and believability.
      SETTING: Waterloo, Ontario, Canada. SUBJECTS: Adults (n 430) aged >=18 years,
      recruited from community settings. RESULTS: Participants in the three FOP
      conditions with 'high/low' sodium content descriptors were significantly more
      likely to choose the lower-sodium product compared with the control group. The
      detailed TL label was ranked most effective at helping participants select low
      sodium products, and was rated significantly higher than other formats in liking,
      understanding and believability. Product selection did not differ significantly
      across sociodemographic groups. CONCLUSIONS: FOP labels that include content
      descriptors may be more effective in helping consumers to select lower-sodium
      products. TL labels, which incorporate content descriptors and colour coding,
      should be considered for future FOP labelling initiatives.

PMID- 22857387
TI  - Translational regulation of Anopheles gambiae mRNAs in the midgut during
      Plasmodium falciparum infection.
AB  - BACKGROUND: Malaria is caused by Plasmodium parasites, which are transmitted via
      the bites of infected Anopheline mosquitoes. Midgut invasion is a major
      bottleneck for Plasmodium development inside the mosquito vectors. Malaria
      parasites in the midgut are surrounded by a hostile environment rich in digestive
      enzymes, while a rapidly responding immune system recognizes Plasmodium ookinetes
      and recruits killing factors from the midgut and surrounding tissues,
      dramatically reducing the population of invading ookinetes before they can
      successfully traverse the midgut epithelium. Understanding molecular details of
      the parasite-vector interactions requires precise measurement of nascent protein
      synthesis in the mosquito during Plasmodium infection. Current expression
      profiling primarily monitors alterations in steady-state levels of mRNA, but does
      not address the equally critical issue of whether the proteins encoded by the
      mRNAs are actually synthesized. RESULTS: In this study, we used sucrose density
      gradient centrifugation to isolate actively translating Anopheles gambiae mRNAs
      based upon their association with polyribosomes (polysomes). The proportion of
      individual gene transcripts associated with polysomes, which is determined by RNA
      deep sequencing, reflects mRNA translational status. This approach led to
      identification of 1017 mosquito transcripts that were primarily regulated at the
      translational level after ingestion of Plasmodium falciparum-infected blood.
      Caspar, a negative regulator of the NF-kappaB transcription factor Rel2, appears
      to be substantially activated at the translational levels during Plasmodium
      infection. In addition, transcripts of Dcr1, Dcr2 and Drosha, which are involved
      in small RNA biosynthesis, exhibited enhanced associations with polysomes after
      P. falciparum challenge. This observation suggests that mosquito microRNAs may
      play an important role in reactions against Plasmodium invasion. CONCLUSIONS: We
      analyzed both total cellular mRNAs and mRNAs that are associated with polysomes
      to simultaneously monitor transcriptomes and nascent protein synthesis in the
      mosquito. This approach provides more accurate information regarding the rate of
      protein synthesis, and identifies some mosquito factors that might have gone
      unrecognized because expression of these proteins is regulated mainly at the
      translational level rather than at the transcriptional level after mosquitoes
      ingest a Plasmodium-infected blood meal.

PMID- 22857388
TI  - Tandem attenuators control expression of the Salmonella mgtCBR virulence operon.
AB  - The mgtCBR operon from Salmonella enterica serovar Typhimurium specifies the
      virulence protein MgtC, the Mg(2+)  transporter MgtB and the regulatory peptide
      MgtR. The mgtCBR transcript includes a long leader region harbouring two short
      open reading frames (ORFs). Translation of these ORFs is anticipated to impact
      the formation of particular stem-loop structures and control transcription of the
      coding region by an attenuation-like mechanism. We previously reported that ORF
      mgtM enables Salmonella to promote transcription of the mgtC and mgtB coding
      regions when experiencing a rise in cytoplasmic ATP levels. We now show that the
      proline codon-rich ORF mgtP mediates an increase in transcription of the mgtC and
      mgtB coding regions under conditions predicted to decrease the levels of proline
      charged tRNA(Pro) . The high ATP and low proline signals act independently in an
      additive form. Replacing conserved mgtP proline codons with codons specifying
      other amino acids abolished the response to proline limitation but had no effect
      on the response to ATP. Substitution of conserved adenine nucleotides in mgtM
      abolished the response to ATP but had no effect in the response to proline
      limitation. This provides a singular example of a leader mRNA with tandem
      attenuators responding to different signals.

PMID- 22857389
TI  - Spontaneous remission of juvenile myelomonocytic leukemia with NRAS mutation.

PMID- 22857390
TI  - Anterior segment fluorescein angiography of the normal feline eye using a dSLR
      camera adaptor.
AB  - PURPOSE: To describe anterior segment fluorescein angiography (ASFA) of the
      normal feline eye using a digital single-lens reflex (dSLR) camera adaptor.
      ANIMALS: Ten cats free of ocular and systemic disease were evaluated. METHODS:
      All cats received maropitant citrate (1.0 mg/kg SQ) and diphenhydramine (2.0
      mg/kg SQ) 20 min prior to anesthesia using propofol (4 mg/kg IV bolus, 0.2
      mg/kg/min CRI). Standard color and red-free images were obtained prior to the
      administration of 10% sodium fluorescein (20 mg/kg IV). Imaging was performed
      using a dSLR camera (Canon 7D), dSLR camera adaptor, camera lens (Canon EF-S 60
      mm f/2.8 macro), and an accessory flash (Canon 580EXII). Imaging occurred at a
      rate of 1/second immediately following IV bolus of sodium fluorescein for a total
      of 30 s, then at 1, 2, 3, 4, 5, and 10 min. RESULTS: Ten cats with an average age
      of 3.7 +/- 0.9 years and various iris colors were imaged. Arterial, capillary,
      and venous phases occurred 4.6, 7.8, and 8.9 s postinjection, respectively.
      Visibility of the vasculature was not impaired by the degree of iris
      pigmentation. Patency of a persistent pupillary membrane was noted in one cat.
      Vessel leakage was common, as well as, leakage into the aqueous humor. Proper
      patient positioning and restricted ocular movements were critical. No adverse
      events were noted. CONCLUSIONS: This study demonstrates ASFA findings in normal
      feline eyes using a cost-effective dSLR camera adaptor. Fluorescein leakage from
      vessels and into the aqueous humor was a common finding. Visibility of iris
      vasculature was not impaired by the degree of iris pigmentation.

PMID- 22857391
TI  - Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a
      case control study.
AB  - BACKGROUND: The Toll-like receptor proteins are important in host defense and
      initiation of the innate and adaptive immune responses. A number of studies have
      identified associations between genetic variation in the Toll-like receptor genes
      and allergic disorders such as asthma and allergic rhinitis. The present study
      aim to search for genetic variation associated with allergic rhinitis in the Toll
      like receptor genes. METHODS: A first association analysis genotyped 73 SNPs in
      182 cases and 378 controls from a Swedish population. Based on these results an
      additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709
      controls and one Chinese population with 948 cases and 580 controls. RESULTS: The
      first association analysis identified 4 allergic rhinitis-associated SNPs in the
      TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified
      7 and 5 significant SNPs from the Swedish and Chinese populations, respectively.
      The corresponding risk-associated haplotypes are significant after Bonferroni
      correction and are the most common haplotypes in both populations. The
      associations are primarily detected in females in the Swedish population, whereas
      it is seen in males in the Chinese population. Further independent support for
      the involvement of this region in allergic rhinitis was obtained from
      quantitative skin prick test data generated in both populations. CONCLUSIONS:
      Haplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in
      one Swedish and one Chinese population. Since this region has earlier been
      associated with asthma and allergic rhinitis in a Danish linkage study this
      speaks strongly in favour of this region being truly involved in the development
      of this disease.

PMID- 22857392
TI  - Association of Hepatitis A exposure and TIM-1 with childhood allergic asthma.
AB  - BACKGROUND: Hepatitis A virus (HAV) receptor (TIM-1) polymorphism plays an
      important role in asthma and autoimmune diseases. Objective. To analyze the
      association of TIM-1 polymorphism and HAV infection with childhood allergic
      asthma in Southwest China. METHODS: TIM-1 exon 4 (157insMTTTVP) and two
      polymorphism loci, -416G>C and -1454G>A, in the HAV receptor promoter region were
      studied. Polymerase chain reaction (PCR) was used to test the genotypes of three
      polymorphism loci among 579 cases of asthma and 524 controls. The HAV infection
      status was determined in a case-control study with stratified analysis. RESULTS:
      HAV exposure associated with childhood allergic asthma in the study population
      was compared with controls (odds ratio (OR) = 0.181, 95% confidence interval (CI)
      0.126-0.260, p < .001). The -416G>C polymorphism was associated with asthma (OR =
      1.384, 95% CI 1.148-1.669, p < .001), but the insertion variant 157delMTTTVP of
      exon 4 and the -1454G>A polymorphism were not. CONCLUSION: Our results indicated
      that the -416G>C polymorphism of the TIM-1 gene is associated with childhood
      allergic asthma, providing a better understanding of the pathogenesis of the
      allergic asthma among children aged below 15 years in Southwest China.

PMID- 22857393
TI  - A generalized strategy for measuring performance in the velocity-position phase
      plane.
AB  - Recent work has proposed the reformulation of smoothness measures derived from
      standard integrated squared jerk, as a function of position, not time. However,
      its promulgation was in the context of monotonic excursion data extracted from
      single degree-of-freedom (DOF) movements; the result was a formulation of a phase
      smoothness measure with limited generalizability. Here, we present a complete
      methodology for implementing the phase smoothness measure in arbitrary datasets,
      i.e. for multi-DOF movements with no assumptions of monotonicity in the kinematic
      profile. Additional suggestions are made for best practices.

PMID- 22857394
TI  - Facile approach for the dispersion of regenerated cellulose in aqueous system in
      the form of nanoparticles.
AB  - This study reports a facile method to disperse cellulose in deionized water,
      wherein a critical condition of regenerated cellulose is discovered, where it
      completely disperses up to a maximum of 5 g L(-1) concentration in deionized
      water with the help of ultrasonication. The dispersed cellulose is characterized
      by TEM and DLS, the latter among which shows 200 nm hydrodynamic radii of
      cellulose nanoparticles dispersed in deionized water. FTIR analysis of dispersed
      cellulose reveals that dispersed cellulose losses its crystallinity during
      regeneration and dispersion step employed in this study. The dispersed cellulose
      reported in this study is able to form free-standing, transparent films, which
      were characterized by SEM, XRD, TGA, EDX, and FTIR spectroscopy and show
      resistance against dissolution in water. Additionally, the dispersed cellulose is
      able to undergo at least three times faster enzymatic hydrolysis in comparison to
      pristine microcrystalline cellulose under similar reaction conditions. The
      dispersed cellulose reported here could be a better material for reinforcement,
      preparation of hydrogels, and drug delivery applications under physiological
      environment.

PMID- 22857395
TI  - Wettability phenomena at the CO2-brine-mineral interface: implications for
      geologic carbon sequestration.
AB  - Geologic carbon sequestration (GCS) in deep saline aquifers results in chemical
      and transport processes that are impacted by the wettability characteristics of
      formation solid phases in contact with connate brines and injected CO(2). Here,
      the contact angle (theta) at the CO(2)-brine-mineral interface is studied for
      several representative solids including quartz, microcline, calcite, kaolinite,
      phlogopite, and illite under a range of GCS conditions. All were found to be
      water wetting (theta < 30 degrees ) with subtle but important differences in
      contact angles observed between the surfaces. Temperature and pressure conditions
      affected the results but did not produce discernible trends common to all
      surfaces. Brine composition, in terms of pH and ionic strength, was a better
      predictor of interfacial behavior. For the nonclays, the wettability is impacted
      by the pH at the point of zero charge of the solid. For the clays, the response
      was more complex. Under nonequilibrium conditions, hysteretic effects were
      observed when CO(2) was dissolving into the bulk fluid and this effect varied
      between minerals. Contact angle was found to decrease during the CO(2) phase
      transition from supercritical or liquid phase to gas phase. These results are
      useful for developing a more complete understanding of leakage through caprocks
      and capillary trapping in GCS.

PMID- 22857396
TI  - Singlet-oxygen-mediated cell death using spatially-localized two-photon
      excitation of an extracellular sensitizer.
AB  - Controlling and quantifying the photosensitized production of singlet oxygen are
      key aspects in mechanistic studies of oxygen-dependent photoinitiated cell death.
      In this regard, the commonly accepted practice of using intracellular
      photosensitizers is, unfortunately, plagued by problems that include the
      inability to accurately (1) quantify the sensitizer concentration in the
      irradiated domain and (2) control the local environment that influences light
      delivery and sensitizer photophysics. However, capitalizing on the fact that
      singlet oxygen produced outside a cell is also cytotoxic, many of these problems
      can be avoided with the use of an extracellular sensitizer. For the present
      study, a hydrophilic dendrimer-encased membrane-impermeable sensitizer was used
      to generate an extracellular population of singlet oxygen upon spatially
      localized two-photon irradiation. Through the use of this sensitizer and this
      approach, it is now possible to better control the singlet oxygen dose in
      microscope-based time- and space-resolved single cell experiments. Thus, we
      provide a solution to a limiting problem in mechanistic studies of singlet-oxygen
      mediated cell death. 

PMID- 22857397
TI  - Methods of monitoring the training and match load and their relationship to
      changes in fitness in professional youth soccer players.
AB  - Previous studies examining methods of monitoring the training and match load in
      soccer players have simply compared those methods to each other, not to changes
      in fitness. Training and match load measures from nine professional youth soccer
      players were collected for a period of six weeks. A lactate threshold test was
      conducted before and after this period. Mean weekly training and match load as
      determined by session-RPE, Banister's TRIMP, Team TRIMP and individualised TRIMP
      (iTRIMP) were correlated with each other, percentage changes in the velocity at 2
      mmol . L(-1) (vLT) and 4 mmol . L(-1) (vOBLA) blood lactate concentration, and
      heart rate at 2 mmol . L(-1) (LT(HR)) and 4 mmol . L(-1) (OBLA(HR)). There were
      no significant changes in fitness across the six weeks: vLT (p = 0.54), vOBLA (p
      = 0.16), LT(HR) (p = 0.51) and OBLA(HR) (p = 0.63). Banister's TRIMP was
      significantly correlated with session-RPE (r = 0.75; p = 0.02) and Team TRIMP (r
      = 0.92; p < 0.001). The percentage change in vLT was significantly correlated to
      mean weekly iTRIMP (r = 0.67; p = 0.04). The results suggest that an
      individualised measure of internal load (iTRIMP) related better than other
      methods to changes in vLT in professional youth soccer players.

PMID- 22857398
TI  - Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant
      enzymes.
AB  - BACKGROUND: Ageing is associated with gastrointestinal dysfunction, which can
      have a major impact on quality of life of the elderly. A number of changes in the
      innervation of the gut during ageing have been reported, including neuronal loss
      and degenerative changes. Evidence indicates that reactive oxygen species (ROS)
      are elevated in ageing enteric neurons, but that neurotrophic factors may reduce
      generation of neuronal ROS. Two such factors, glial cell line derived
      neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to
      protect enteric neurons against oxidative stress induced cell death of enteric
      ganglion cells in vitro. We have investigated the possible roles of neurotrophic
      factors further, by examining their expression in the gut during ageing, and by
      analysing their effects on antioxidant enzyme production in cultures of enteric
      ganglion cells. RESULTS: Analysis of the expression of GDNF and its receptors c
      Ret and GFR alpha - 1 in rat gut by RT-PCR showed that expression continues
      throughout life and into ageing, in both ad libitum(AL) and calorically
      restricted (CR) animals. Levels of expression of GDNF and GFR alpha - 1 were
      elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and
      6 month control animals respectively. The related factor Neurturin and its
      receptor GFR alpha - 2 were also expressed throughout life, the levels of the GFR
      - alpha-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that
      c-Ret and GFR alpha - 1 proteins were expressed by myenteric neurons in ageing
      animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide
      dismutase and catalase by cultured enteric ganglion cells. CONCLUSIONS: The
      neurotrophic factors GDNF and neurturin and their receptors continue to be
      expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR
      alpha-1 and GFR alpha-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT
      3, increased the levels of antioxidant enzymes in cultured enteric ganglion
      cells, indicating a possible mechanism for the reported protective effect of GDNF
      against menadione-induced neuronal apoptosis in the ageing gut. Together these
      data suggest that GDNF family members may play a protective role in the gut
      throughout life, and support the suggestion that dysregulation of neurotrophic
      factor support could contribute to neuronal ageing in the gut.

PMID- 22857399
TI  - A scoping review about conference objectives and evaluative practices: how do we
      get more out of them?
AB  - Large multi-day conferences have often been criticized as ineffective ways to
      improve social outcomes and to influence policy or practice. Unfortunately, many
      conference evaluations have also been inadequate in determining the impact of a
      conference on its associated social sector, with little evidence gathered or
      analyzed to substantiate or refute these criticisms. The aim of this scoping
      review is to investigate and report stakeholders' objectives for planning or
      participating in large multi-day conferences and how these objectives are being
      evaluated. We conducted a scoping review supplemented by a small number of key
      informant interviews. Eight bibliographic databases were systematically searched
      to identify papers describing conference objectives and/or evaluations. We
      developed a conference evaluation framework based on theoretical models and
      empirical findings, which structured the descriptive synthesis of the data. We
      identified 3,073 potential papers for review, of which 44 were included in this
      study. Our evaluation framework connects five key elements in planning a
      conference and its evaluation (number in brackets refers to number of themes
      identified): conference objectives (8), purpose of evaluation (7), evaluation
      methods (5), indicators of success (9) and theories/models (8). Further analysis
      of indicators of success identified three categories of indicators with differing
      scopes (i.e. immediate, prospective or follow-up) as well as empirical links
      between the purpose of evaluations and these indicators. Conference objectives
      and evaluations were largely correlated with the type of conference (i.e.
      academic, political/governmental or business) but diverse overall. While much can
      be done to improve the quality and usefulness of conference evaluations, there
      are innovative assessments that are currently being utilized by some conferences
      and warrant further investigation. This review provides conference evaluators and
      organizers a simple resource to improve their own assessments by highlighting and
      categorizing potential objectives and evaluation strategies.

PMID- 22857400
TI  - Dependence of alpha-helical and beta-sheet amino acid propensities on the overall
      protein fold type.
AB  - BACKGROUND: A large number of studies have been carried out to obtain amino acid
      propensities for alpha-helices and beta-sheets. The obtained propensities for
      alpha-helices are consistent with each other, and the pair-wise correlation
      coefficient is frequently high. On the other hand, the beta-sheet propensities
      obtained by several studies differed significantly, indicating that the context
      significantly affects beta-sheet propensity. RESULTS: We calculated amino acid
      propensities for alpha-helices and beta-sheets for 39 and 24 protein folds,
      respectively, and addressed whether they correlate with the fold. The
      propensities were also calculated for exposed and buried sites, respectively.
      Results showed that alpha-helix propensities do not differ significantly by fold,
      but beta-sheet propensities are diverse and depend on the fold. The propensities
      calculated for exposed sites and buried sites are similar for alpha-helix, but
      such is not the case for the beta-sheet propensities. We also found some fold
      dependence on amino acid frequency in beta-strands. Folds with a high Ser, Thr
      and Asn content at exposed sites in beta-strands tend to have a low Leu, Ile,
      Glu, Lys and Arg content (correlation coefficient = -0.90) and to have flat beta
      sheets. At buried sites in beta-strands, the content of Tyr, Trp, Gln and Ser
      correlates negatively with the content of Val, Ile and Leu (correlation
      coefficient = -0.93). "All-beta" proteins tend to have a higher content of Tyr,
      Trp, Gln and Ser, whereas "alpha/beta" proteins tend to have a higher content of
      Val, Ile and Leu. CONCLUSIONS: The alpha-helix propensities are similar for all
      folds and for exposed and buried residues. However, beta-sheet propensities
      calculated for exposed residues differ from those for buried residues, indicating
      that the exposed-residue fraction is one of the major factors governing amino
      acid composition in beta-strands. Furthermore, the correlations we detected
      suggest that amino acid composition is related to folding properties such as the
      twist of a beta-strand or association between two beta sheets.

PMID- 22857402
TI  - Improving influenza immunization rates through a specialized clinic review.
AB  - PURPOSE: The purpose of this capstone project was to determine if alternative
      access by way of a focused immunization clinic rather than a regular physician
      office visit caused an increase from 2009 to 2010 in the number of people in a
      rural community who received the influenza vaccine. Reasons why the immunization
      clinic was chosen by the patient for immunization were identified. METHODS: This
      project was conducted by using a descriptive survey design. A questionnaire was
      given to individuals who participated in an influenza immunization clinic in a
      rural community in a southeastern state. Data were collected using a seven-item
      questionnaire completed by participants. RESULTS: Evaluation of data revealed
      that 40% of individuals who did not receive their vaccine in 2009 received a flu
      shot in 2010 through access to the immunization clinic. CONCLUSION: Evidence
      suggests that providing alternative access to immunizations in a rural community
      could potentially improve the rate of participation of individuals.

PMID- 22857403
TI  - Impact of the environment on asthma control.
AB  - Asthma is a complex condition that requires individualized interventions. The
      purpose of this article is to describe the relationship between the physical and
      social environments with asthma symptoms, present evidence that supports
      environmental interventions in asthma control and the implications for asthma
      management. There is evidence that indoor and outdoor allergens relate to asthma
      morbidity. Knowledge about which environmental exposures present risk is
      essential because many of these exposures can be modified, reduced, or
      eliminated. The community health nurse should provide care relative to the
      client's indoor and outdoor environment and existing allergens.

PMID- 22857404
TI  - Compulsive hoarding: overview and implications for community health nurses.
AB  - Hoarding is a serious public health hazard that poses significant health and
      safety risks for individuals, families, and communities. Research indicates that
      compulsive hoarding is a growing social and environmental problem across the
      United States, affecting as many as 2-5% of the population. Hoarders often live
      chaotically in their own private clutter until it spreads so far that it evolves
      into medical emergencies or can only be contained by the law. Visiting clients in
      their homes provides community health nurses with the unique opportunity to
      identify cases of hoarding and connect individuals and their families with
      appropriate resources, potentially preventing catastrophic outcomes.
      Interventions such as case-finding, outreach, case management, community
      education, and advocacy may be implemented by the community health nurse to
      improve the health of this very vulnerable population. The aim of this article is
      to inform community health nurses of the complexity of this emerging phenomenon,
      its symptoms, treatments, and impacts on individuals, their families, and their
      communities.

PMID- 22857405
TI  - The relationship between repeated unintended pregnancies and current
      contraceptive use: National Survey of Family Growth (NSFG) 2006-2008 data.
AB  - The purpose of this study is to examine the relationship between the number of
      unintended pregnancies and current contraceptive use. This is a secondary
      analysis of a cross-sectional survey, the 2006-2008 National Survey of Family
      Growth, which included 4,052 women between the ages of 15 and 44 years. A
      statistically significant association was found between the nonuse of
      contraceptives and repeated unintended pregnancies, as well as among those who
      used an effective contraceptive method and repeated unintended pregnancies.
      Nurses are encouraged to ask questions about intendedness of pregnancies during
      women's visits and help women choose appropriate contraceptive methods.

PMID- 22857406
TI  - The role of rape myth acceptance in the social norms regarding sexual behavior
      among college students.
AB  - This study examined the antecedents for the acceptance of rape myths. The
      information motivation behavioral skills model was the basis for this study. In
      this cross-sectional study at a northeastern university, 237 students consented
      to participate in an online survey examining knowledge, social norms regarding
      sexual behavior, future time perspective, and rape myth acceptance (RMA). The
      majority of the sample was female. Forty-one percent believed that a woman who
      was raped while drunk was responsible. Men had higher RMA and the less sexual
      knowledge they had, the more they accepted the rape myths. Direction is provided
      regarding primary prevention of sexual assault.

PMID- 22857513
TI  - Editorial : recent strategies in gene delivery.

PMID- 22857512
TI  - Chemical, genetic and structural assessment of pyridoxal kinase as a drug target
      in the African trypanosome.
AB  - Pyridoxal-5'-phosphate (vitamin B(6) ) is an essential cofactor for many
      important enzymatic reactions such as transamination and decarboxylation. African
      trypanosomes are unable to synthesise vitamin B(6) de novo and rely on uptake of
      B(6) vitamers such as pyridoxal and pyridoxamine from their hosts, which are
      subsequently phosphorylated by pyridoxal kinase (PdxK). A conditional null mutant
      of PdxK was generated in Trypanosoma brucei bloodstream forms showing that this
      enzyme is essential for growth of the parasite in vitro and for infectivity in
      mice. Activity of recombinant T. brucei PdxK was comparable to previously
      published work having a specific activity of 327 +/- 13 mU mg(-1) and a K(m)(app)
      with respect to pyridoxal of 29.6 +/- 3.9 uM. A coupled assay was developed
      demonstrating that the enzyme has equivalent catalytic efficiency with pyridoxal,
      pyridoxamine and pyridoxine, and that ginkgotoxin is an effective pseudo
      substrate. A high resolution structure of PdxK in complex with ATP revealed
      important structural differences with the human enzyme. These findings suggest
      that pyridoxal kinase is an essential and druggable target that could lead to
      much needed alternative treatments for this devastating disease.

PMID- 22857514
TI  - P53 and cellular glucose uptake.
AB  - OBJECTIVES: Tumor protein p53 is a transcription factor involved with cellular
      responses to stressors including limited glucose availability. We hypothesized
      that modulating p53 levels would affect cellular glucose uptake. METHODS AND
      RESULTS: Transfecting cultured primary mouse hepatocytes with p53 siRNA
      suppressed p53 mRNA expression >90%. Control hepatocytes (transfected with non
      targeting siRNA) increased glucose uptake (2.28 +/- 1.02-fold vs basal, p 0.009)
      in response to 100 nM insulin, but p53 siRNA-treated hepatocytes had a blunted
      response (0.92 +/- 0.11-fold vs basal; between group difference p 0.0012). In
      adipocytes differentiated from the pre-adipocyte line 3T3-L1, knockdown of p53
      had no effect on insulin-stimulated glucose uptake. There were no differences in
      Glut 1 or Glut 2 expression in the plasma membrane fraction or in the levels of
      phosphorylated AKT in cell lysates between primary hepatocytes transfected with
      p53 siRNA or control siRNA. Glycemic responses to insulin tolerance, glucose
      tolerance, and pyruvate tolerance tests did not differ between p53 knockout and
      wild type mice. DISCUSSION: Thus, inhibition of p53 has pleiotropic effects,
      inhibiting glucose uptake in the liver but having no effect on adipocytes.
      Knockout of p53 has no apparent effect on glucose homeostasis in intact lean
      mice. An explanation for the association between p53 expression and hepatocyte
      glucose uptake remains to be elucidated.

PMID- 22857515
TI  - Sources of Verticillium dahliae affecting lettuce.
AB  - ABSTRACT   Since 1995, lettuce in coastal California, where more than half of the
      crop in North America is grown, has consistently suffered from severe outbreaks
      of Verticillium wilt. The disease is confined to this region, although the
      pathogen (Verticillium dahliae) and the host are present in other crop production
      regions in California. Migration of the pathogen with infested spinach seed was
      previously documented, but the geographic sources of the pathogen, as well as the
      impact of lettuce seed sparsely infested with V. dahliae produced outside coastal
      California on the pathogen population in coastal California remain unclear.
      Population analyses of V. dahliae were completed using 16 microsatellite markers
      on isolates from lettuce plants in coastal California, infested lettuce seed
      produced in the neighboring Santa Clara Valley of California, and spinach seed
      produced in four major spinach seed production regions: Chile, Denmark, the
      Netherlands, and the United States (Washington State). California produces 80% of
      spinach in the United States and all seed planted with the majority infested by
      V. dahliae comes from the above four sources. Three globally distributed genetic
      populations were identified, indicating sustained migration among these distinct
      geographic regions with multiple spinach crops produced each year and repeated
      every year in coastal California. The population structure of V. dahliae from
      coastal California lettuce plants was heavily influenced by migration from
      spinach seed imported from Denmark and Washington. Conversely, the sparsely
      infested lettuce seed had limited or no contribution to the Verticillium wilt
      epidemic in coastal California. The global trade in plant and seed material is
      likely contributing to sustained shifts in the population structure of V.
      dahliae, affecting the equilibrium of native populations, and likely affecting
      disease epidemiology.

PMID- 22857516
TI  - Hypovirus virulence and vegetative incompatibility in populations of the chestnut
      blight fungus.
AB  - Cryphonectria hypovirus 1 hyperparasitizes the chestnut blight fungus
      Cryphonectria parasitica and acts as a biocontrol agent for this serious tree
      disease. The virus is transmitted cytoplasmatically between fungal individuals.
      However, highly virulent viruses strongly debilitate their host and, thus, reduce
      their own transmission probability. Furthermore, vegetative incompatibility
      between fungi is an important transmission barrier. Therefore, virulent viruses
      are expected to be strongly selected against in fungal populations with high
      levels of vegetative incompatibility, eventually leading to the erosion of
      biocontrol. To test this prediction, we assessed the virulence of the virus in
      four European C. parasitica populations with high diversity of vegetative
      compatibility types and in four populations with low diversity. We expected the
      degree of virus virulence to be lower in fungal populations with high levels of
      vegetative incompatibility. However, our results did not reveal such a trend. No
      significant differences in virus virulence between populations with low versus
      high diversity of vegetative compatibility types were observed. There was no
      evidence for an erosion of disease control due to the presence of these
      transmission barriers. Thus, the findings of this study are promising for the
      sustainability of Cryphonectria hypovirus 1 as a biocontrol agent for chestnut
      blight in Europe.

PMID- 22857518
TI  - Validity and reliability of the TGMD-2 for Brazilian children.
AB  - The Test of Gross Motor Development (TGMD-2) is broadly used in research and
      clinical settings. The author aimed to translate and investigate the content,
      criteria, and construct validity and reliability of the TGMD-2 for Brazilian
      children. The study involved translators, experts, and 3,124 Brazilian children
      from several states of Brazil. Results confirmed language clarity and pertinence
      of the TGMD-2. Appropriate indices of the confirmatory factorial validity (root
      mean square error of approximation = .06; comparative fit index = .88; Tucker
      Lewis index = .83; normed fit index = .09; goodness-of-fit index = .98; adjusted
      goodness-of-fit index = .95), test-retest (values from .83 to .91) and inter- and
      intrarater reliability were found. Concurrent validity between TGMD-2 and
      Movement Assessment Battery for Children was weak. The TGMD-2 is a validity and
      reliability instrument for Brazilian children.

PMID- 22857517
TI  - Shared meals among young adults are associated with better diet quality and
      predicted by family meal patterns during adolescence.
AB  - OBJECTIVE: To describe shared meal patterns and examine associations with dietary
      intake among young adults. DESIGN: Population-based, longitudinal cohort study
      (Project EAT: Eating and Activity in Teens and Young Adults). SETTING:
      Participants completed surveys and FFQ in high-school classrooms in
      Minneapolis/St. Paul, MN, USA in 1998-1999 (mean age = 15.0 years, 'adolescence')
      and follow-up measures online or by mail in 2008-2009 (mean age = 25.3 years,
      'young adulthood'). SUBJECTS: There were 2052 participants who responded to the
      10-year follow-up survey and reported on frequency of having shared meals.
      RESULTS: Among young adults, the frequency of shared meals during the past week
      was as follows: never (9.9 %), one or two times (24.7 %), three to six times
      (39.1 %) and seven or more times (26.3 %). Having more frequent family meals
      during adolescence predicted a higher frequency of shared meals in young
      adulthood above and beyond other relevant sociodemographic factors such as
      household composition and parental status. Compared with young adults who never
      had family meals during adolescence, those young adults who reported seven or
      more family meals per week during adolescence had an average of one additional
      shared meal per week. Having more frequent shared meals in young adulthood was
      associated with greater intake of fruit among males and females, and with higher
      intakes of vegetables, milk products and some key nutrients among females.
      CONCLUSIONS: Nutrition professionals should encourage families of adolescents to
      share meals often and establish the tradition of eating together, and work with
      young adults to ensure that healthy food and beverage choices are offered at
      mealtimes.

PMID- 22857519
TI  - Advances in determining the absolute proton affinities of neutral organic
      molecules in the gas phase and their interpretation: a theoretical account.

PMID- 22857520
TI  - Synthesis and characterization of the crystal structure and magnetic properties
      of the new fluorophosphate LiNaCo[PO4]F.
AB  - The new compound LiNaCo[PO(4)]F was synthesized by a solid state reaction route,
      and its crystal structure was determined by single-crystal X-ray diffraction
      measurements. The magnetic properties of LiNaCo[PO(4)]F were characterized by
      magnetic susceptibility, specific heat, and neutron powder diffraction
      measurements and also by density functional calculations. LiNaCo[PO(4)]F
      crystallizes with orthorhombic symmetry, space group Pnma, with a = 10.9334(6), b
      = 6.2934(11), c = 11.3556(10) A, and Z = 8. The structure consists of edge
      sharing CoO(4)F(2) octahedra forming CoFO(3) chains running along the b axis.
      These chains are interlinked by PO(4) tetrahedra forming a three-dimensional
      framework with the tunnels and the cavities filled by the well-ordered sodium and
      lithium atoms, respectively. The magnetic susceptibility follows the Curie-Weiss
      behavior above 60 K with theta = -21 K. The specific heat and magnetization
      measurements show that LiNaCo[PO(4)]F undergoes a three-dimensional magnetic
      ordering at T(mag) = 10.2(5) K. The neutron powder diffraction measurements at 3
      K show that the spins in each CoFO(3) chain along the b-direction are
      ferromagnetically coupled, while these FM chains are antiferromagnetically
      coupled along the a-direction but have a noncollinear arrangement along the c
      direction. The noncollinear spin arrangement implies the presence of spin
      conflict along the c-direction. The observed magnetic structures are well
      explained by the spin exchange constants determined from density functional
      calculations.

PMID- 22857521
TI  - Mechanistic insights into phosphopeptide--BRCT domain association:
      preorganization, flexibility, and phosphate recognition.
AB  - Promiscuous proteins are commonly observed in biological systems, for example, in
      modular domains that recognize phosphopeptides during signal transduction. This
      promiscuous recognition is of fundamental interest in chemistry and biology but
      is challenging when designing phosphopeptides in silico for cell biology studies.
      To investigate promiscuous recognition and binding processes of phosphopeptides
      and the modular domain, we selected a domain essential in breast cancer-the
      breast-cancer-associated protein 1 (BRCA1) C-terminal (BRCT) repeats as our model
      system. We performed molecular dynamics simulations and detailed analyses of the
      dihedral space to study protein fluctuation and conformational changes with
      phosphopeptide binding. We also studied the association processes of
      phosphorylated and unphosphorylated peptides using Brownian dynamics with a
      coarse-grained model. We found that the BRCT domain is preorganized for
      phosphopeptide binding but has a moderate arrangement of side chains to form
      complexes with various types of phosphopeptides. Phosphopeptide binding restricts
      the system motion in general, while the nonpolar phosphopeptide becomes more
      flexible in the bound state. Our analysis found that the BRCT domain utilizes
      different mechanisms, usually termed lock and key, induced-fit, and population
      shift/conformational-selection models, to recognize peptides with different
      features. Brownian dynamics simulations revealed that the charged phosphate group
      may not always accelerate peptide association processes, but it helps the
      phosphopeptide orient into binding pockets accurately and stabilizes the complex.
      This work provides insights into molecular recognition in the promiscuous protein
      system. 

PMID- 22857522
TI  - A three-dimensional topology of complex I inferred from evolutionary
      correlations.
AB  - BACKGROUND: The quaternary structure of eukaryotic NADH:ubiquinone oxidoreductase
      (complex I), the largest complex of the oxidative phosphorylation, is still
      mostly unresolved. Furthermore, it is unknown where transiently bound assembly
      factors interact with complex I. We therefore asked whether the evolution of
      complex I contains information about its 3D topology and the binding positions of
      its assembly factors. We approached these questions by correlating the
      evolutionary rates of eukaryotic complex I subunits using the mirror-tree method
      and mapping the results into a 3D representation by multidimensional scaling.
      RESULTS: More than 60% of the evolutionary correlation among the conserved seven
      subunits of the complex I matrix arm can be explained by the physical distance
      between the subunits. The three-dimensional evolutionary model of the eukaryotic
      conserved matrix arm has a striking similarity to the matrix arm quaternary
      structure in the bacterium Thermus thermophilus (rmsd=19 A) and supports the
      previous finding that in eukaryotes the N-module is turned relative to the Q
      module when compared to bacteria. By contrast, the evolutionary rates contained
      little information about the structure of the membrane arm. A large evolutionary
      model of 45 subunits and assembly factors allows to predict subunit positions and
      interactions (rmsd=52.6 A). The model supports an interaction of NDUFAF3, C8orf38
      and C2orf56 during the assembly of the proximal matrix arm and the membrane arm.
      The model further suggests a tight relationship between the assembly factor NUBPL
      and NDUFA2, which both have been linked to iron-sulfur cluster assembly, as well
      as between NDUFA12 and its paralog, the assembly factor NDUFAF2. CONCLUSIONS: The
      physical distance between subunits of complex I is a major correlate of the rate
      of protein evolution in the complex I matrix arm and is sufficient to infer parts
      of the complex's structure with high accuracy. The resulting evolutionary model
      predicts the positions of a number of subunits and assembly factors.

PMID- 22857524
TI  - Non-isothermal kinetics of thermal degradation of chitosan.
AB  - BACKGROUND: Chitosan is the second most abundant nitrogen containing biopolymer
      in nature, obtained from the shells of crustaceans, particularly crabs, shrimp
      and lobsters, which are waste products of seafood processing industries. It has
      great potential application in the areas of biotechnology, biomedicine, food
      industries, and cosmetics. Chitosan is also capable of adsorbing a number of
      metal ions as its amino groups can serve as chelation sites. Grafted functional
      groups such as hydroxyl, carboxyl, sulfate, phosphate, and amino groups on the
      chitosan have been reported to be responsible for metal binding and sorption of
      dyes and pigments. The knowledge of their thermal stability and pyrolysis may
      help to better understand and plan their industrial processing. RESULTS:
      Thermogravimetric studies of chitosan in air atmosphere were carried out at six
      rates of linear increasing of the temperature. The kinetics and mechanism of the
      thermal decomposition reaction were evaluated from the TG data using recommended
      from ICTAC kinetics committee iso-conversional calculation procedure of Kissinger
      Akahira-Sunose, as well as 27 mechanism functions. The comparison of the obtained
      results showed that they strongly depend on the selection of proper mechanism
      function for the process. Therefore, it is very important to determine the most
      probable mechanism function. In this respect the iso-conversional calculation
      procedure turned out to be the most appropriate. CONCLUSION: Chitosan have
      excellent properties such as hydrophilicity, biocompatibility, biodegradability,
      antibacterial, non-toxicity, adsorption application. The thermal degradation of
      chitosan occurs in two stages. The most probable mechanism function for both
      stages is determined and it was best described by kinetic equations of n-th order
      (Fn mechanism). For the first stage, it was established that n is equal to 3.0
      and for the second stage - to 1.0 respectively. The values of the apparent
      activation energy E, pre-exponential factor A in Arrhenius equation, as well as
      the changes of entropy DeltaS?, enthalpy DeltaH? and free Gibbs energy DeltaG?
      for the formation of the activated complex from the reagent are calculated.

PMID- 22857523
TI  - Evidence for sequence biases associated with patterns of histone methylation.
AB  - BACKGROUND: Combinations of histone variants and modifications, conceptually
      representing a histone code, have been proposed to play a significant role in
      gene regulation and developmental processes in complex organisms. While various
      mechanisms have been implicated in establishing and maintaining epigenetic
      patterns at specific locations in the genome, they are generally believed to be
      independent of primary DNA sequence on a more global scale. RESULTS: To address
      this systematically in the case of the human genome, we have analyzed primary DNA
      sequences underlying patterns of 19 different methylated histones in human
      primary T-cells and patterns of three methylated histones across additional human
      cell lines. We report strong sequence biases associated with most of these
      histone marks genome-wide in each cell type. Furthermore, the sequence
      characteristics for such association are distinct for different groups of histone
      marks. CONCLUSIONS: These findings provide evidence of an influence of genomic
      sequence on patterns of histone modification associated with gene expression and
      chromatin programming, and they suggest that the mechanisms responsible for
      global histone modifications may interpret genomic sequence in various ways.

PMID- 22857525
TI  - Development of continuous pharmaceutical production processes supported by
      process systems engineering methods and tools.

PMID- 22857526
TI  - Blocking pathogen entry into the cell: the future of infectious disease treatment
      and control?

PMID- 22857527
TI  - Peptides could be used as anti-inflammatory agents in severe malaria.
AB  - Australia-based researchers demonstrate the potential use of innate defense
      regulator proteins to treat inflammation in malaria sufferers.

PMID- 22857528
TI  - Ask the experts.
AB  - The Uniting to Combat Neglected Tropical Diseases partners, including the US, UK,
      UAE and other national governments, along with 13 pharmaceutical industry
      businesses, the World Bank, the Bill and Melinda Gates Foundation, and other
      neglected tropical disease-endemic countries, announced that they are to join
      together to drive research and innovation for the treatment of neglected tropical
      diseases. The collaboration will see neglected tropical disease-endemic countries
      work alongside these organizations with the goal of fueling R&D of treatments for
      ten neglected tropical diseases in support of WHO's 2020 goals. Isaac Bruce,
      Commissioning Editor, spoke to four experts in the field from academia, not-for
      profit organizations and the pharmaceutical industry, and asked their opinions on
      the partnerships announced and what the status of neglected tropical disease
      research will be at the end of this decade.

PMID- 22857529
TI  - Lab reports and cat scans: can veterinary oncology guide our way to new
      treatments for human cancers?

PMID- 22857530
TI  - Use of the electronic laboratory notebook to facilitate green chemistry within
      the pharmaceutical industry.

PMID- 22857531
TI  - Electron density study of the anti-Alzheimer's disease drug donepezil from
      conventional x-ray data and invariom database application.
AB  - BACKGROUND: The crystal structures of a very large number of compounds with
      biological relevance are known. Application of the invariom formalism provides
      the aspherical electron density distribution. RESULTS AND DISCUSSION: The
      electron density distribution of the anti-Alzheimer's disease drug donepezil was
      derived from its x-ray structure reported in the literature, using the invariom
      database. The electrostatic potential mapped on the electron density isosurface
      shows how the positive charge of the donepezilium cation is distributed over a
      wide surface range. The presence of intermolecular contacts can be illustrated by
      the Hirshfeld surface. Comparable interactions are found in both the small
      molecule structure and an acetylcholinesterase complex with donezepil from the
      literature. CONCLUSION: The electron density of donepezil in the small-molecule
      crystal structure mimics the intermolecular interactions within the receptor
      site. Complementing steric properties with electronic information can be a
      valuable procedure in the examination of molecular recognition of systems with
      biological activity.

PMID- 22857532
TI  - Macrocycles in new drug discovery.
AB  - The use of drug-like macrocycles is emerging as an exciting area of medicinal
      chemistry, with several recent examples highlighting the favorable changes in
      biological and physicochemical properties that macrocyclization can afford.
      Natural product macrocycles and their synthetic derivatives have long been
      clinically useful and attention is now being focused on the wider use of
      macrocyclic scaffolds in medicinal chemistry in the search for new drugs for
      increasingly challenging targets. With the increasing awareness of concepts of
      drug-likeness and the dangers of 'molecular obesity', functionalized macrocyclic
      scaffolds could provide a way to generate ligand-efficient molecules with
      enhanced properties. In this review we will separately discuss the effects of
      macrocyclization upon potency, selectivity and physicochemical properties,
      concentrating on recent case histories in oncology drug discovery. Additionally,
      we will highlight selected advances in the synthesis of macrocycles and provide
      an outlook on the future use of macrocyclic scaffolds in medicinal chemistry.

PMID- 22857533
TI  - Histone deacetylase inhibitors in the treatment of cancer: overview and
      perspectives.
AB  - Histone deacetylase inhibitors (HDACis) are one of the last frontiers in
      pharmaceutical research. Several classes of HDACi have been identified. Although
      more than 20 HDACi are under preclinical and clinical investigation as single
      agents and in combination therapies against different cancers, just two of them
      were approved by the US FDA: Zolinza((r)) and Istodax((r)), both licensed for the
      treatment of cutaneous T-cell lymphoma, the latter also of peripheral T-cell
      lymphoma. Since HDAC enzymes act by forming multiprotein complexes (clusters),
      containing cofactors, the main problem in designing new HDACi is that the
      inhibition activity evaluated on isolated enzyme isoforms does not match the in
      vivo outcomes. In the coming years, the research will be oriented toward a better
      understanding of the functioning of these protein complexes as well as the
      development of new screening assays, with the final goal to obtain new drug
      candidates for the treatment of cancer.

PMID- 22857534
TI  - Nucleoside transporters: biological insights and therapeutic applications.
AB  - Nucleoside transporters play important physiological roles by regulating intra-
      and extra-cellular concentrations of purine and pyrimidine (deoxy)nucleosides.
      This review describes the biological function and activity of the two major
      families of membrane nucleoside transporters that exist in mammalian cells. These
      include equilibrative nucleoside transporters that transport nucleosides in a
      gradient-dependent fashion and concentrative nucleoside transporters that import
      nucleosides against a gradient by coupling movement with sodium transport.
      Particular emphasis is placed on describing the roles of nucleoside transport in
      normal physiological processes, including inflammation, cardiovascular function
      and nutrient transport across the blood-brain barrier. In addition, the role of
      nucleoside transport in pathological conditions such as cardiovascular disease
      and cancer are discussed. The potential therapeutic applications of manipulating
      nucleoside transport activities are discussed, focusing on nucleoside analogs as
      anti-neoplastic agents. Finally, we discuss future directions for the development
      of novel chemical entities to measure nucleoside transport activity at the
      cellular and organismal level.

PMID- 22857535
TI  - Quantum kernel applications in medicinal chemistry.
AB  - Progress in the quantum mechanics of biological molecules is being driven by
      computational advances. The notion of quantum kernels can be introduced to
      simplify the formalism of quantum mechanics, making it especially suitable for
      parallel computation of very large biological molecules. The essential idea is to
      mathematically break large biological molecules into smaller kernels that are
      calculationally tractable, and then to represent the full molecule by a summation
      over the kernels. The accuracy of the kernel energy method (KEM) is shown by
      systematic application to a great variety of molecular types found in biology.
      These include peptides, proteins, DNA and RNA. Examples are given that explore
      the KEM across a variety of chemical models, and to the outer limits of energy
      accuracy and molecular size. KEM represents an advance in quantum biology
      applicable to problems in medicine and drug design.

PMID- 22857536
TI  - Bismuth compounds in medicinal chemistry.
AB  - In recent years, the chemical potential of bismuth and bismuth compounds has been
      actively exploited. Bismuth salts are known for their low toxicity, making them
      potential valuable reagents for large-scale synthesis, which becomes more obvious
      when dealing with products such as active pharmaceutical ingredients or synthetic
      intermediates. Conversely, bismuth compounds have been widely used in medicine.
      After extensive use in the treatments of syphilis and other bacterial infections
      before the advent of modern antibiotics, bismuth compounds remain important for
      the treatment of several gastrointestinal disorders and also exhibit
      antimicrobial properties and cytotoxic activity, among others. This review
      updates relevant advances in the past few years, concerning the application of
      bismuth reagents and catalysts in innovative synthetic processes for the
      preparation of compounds of medicinal interest, as well as the preparation,
      biological evaluation and potential medicinal uses of bismuth compounds.

PMID- 22857538
TI  - A modeled economic evaluation of sevelamer for treatment of hyperphosphatemia
      associated with chronic kidney disease among patients on dialysis in the United
      Kingdom.
AB  - OBJECTIVE: There is limited information regarding the cost-effectiveness of
      sevelamer for the treatment of hyperphosphatemia in chronic kidney disease (CKD)
      patients on dialysis in the UK. Using a UK National Health Service (NHS)
      perspective and final results of the Dialysis Clinical Outcomes Revisited (DCOR)
      study, an evaluation was performed to determine the cost-effectiveness of
      sevelamer compared to calcium-based phosphate binders for the first-line
      treatment of hyperphosphatemia in CKD patients on dialysis. METHODS: A Markov
      model was developed to estimate life years, quality-adjusted life years (QALYs),
      costs, incremental cost per life year (LY) gained, and QALY gained. Treatment
      specific overall survival up to 44 months, hospitalizations, and resource
      utilization were derived from the DCOR study. Survival was extrapolated to a
      lifetime horizon using Weibull regression analysis. Unit costs and utility
      estimates specific to the UK were obtained from the published literature. Sub
      group analyses were conducted based on data reported from the DCOR study for
      increasing age cut-points. Outcomes and costs were modeled for a lifetime
      horizon. RESULTS: In the base case analysis, the use of sevelamer resulted in a
      gain of ~0.73 LYs and 0.44 QALYs per patient (discounted at 3.5% per year). Total
      per-patient costs were higher for sevelamer, resulting in an incremental cost of
      L22,157 per QALY gained and L13,427 per LY gained (in L2009). Increasingly
      favorable cost per QALY ratios were observed with increasing age cut-points,
      ranging from L15,864 for patients >=45 to L13,296 for patients >=65 years of age.
      Results were most sensitive to assumptions regarding overall survival and the
      inclusion of dialysis costs. Key limitations of the analysis included the use of
      non-UK trial data for survival and hospitalizations, and the exclusion of quality
      of-life impacts associated with hospitalization. CONCLUSIONS: In CKD patients
      receiving dialysis, treatment of hyperphosphatemia with sevelamer offers good
      value for money compared with calcium-based binders.

PMID- 22857539
TI  - One-year follow-up healthcare costs of patients hospitalized for transient
      ischemic attack or ischemic stroke and discharged with aspirin plus extended
      release dipyridamole or clopidogrel.
AB  - OBJECTIVE: To examine healthcare costs among patients hospitalized for transient
      ischemic attack or ischemic stroke (TIA/stroke) and prescribed aspirin plus
      extended-release dipyridamole (ASA-ERDP) or clopidogrel (CLOPID) within 30 days
      post-discharge using a retrospective claims database from a large US managed care
      organization. METHODS: Adult patients with >=1 hospitalizations for TIA/stroke
      between January 2007-July 2009 and >=1 claims for an oral anti-platelet (OAP)
      were observed for 1 year before and after the first TIA/stroke hospitalization or
      until death, whichever came first. Cohorts were defined by the first claim for
      ASA-ERDP or CLOPID within 30 days post-discharge. A generalized linear model,
      adjusting for demographics, baseline comorbidities and costs, compared total
      follow-up costs (medical + pharmacy) between ASA-ERDP and CLOPID patients.
      RESULTS: Of 6377 patients (2085 ASA-ERDP; 4292 CLOPID) who met the selection
      criteria, mean (SD) age was 69 (13) years and 50% were male. Unadjusted mean
      total follow-up costs were lower for ASA-ERDP than CLOPID ($26,201 vs $30,349;
      p=0.002), of which average unadjusted medical and pharmacy costs were $22,094 vs
      $26,062 (p=0.003) and $4107 vs $4288 (p=0.119), respectively. Multivariate
      modeling indicated that the following were associated with higher total costs
      (all p<0.05): higher baseline Quan-Charlson comorbidity score, history of atrial
      fibrillation and myocardial infarction, index stroke hospitalization, death post
      discharge, and index CLOPID use. Adjusted mean total follow-up costs for CLOPID
      were 9% higher than ASA-ERDP (cost ratio: 1.09; p=0.038). CONCLUSION: In this
      study, compared to CLOPID patients, ASA-ERDP patients were observed to have lower
      total costs 1 year post-discharge TIA/stroke hospitalization, driven primarily by
      lower medical costs. Further research into the real-world impact of OAP therapies
      on clinical and economic outcomes of patients with stroke/TIA is warranted. The
      findings of this study should be considered within the limitations of an
      administrative claims analysis, as claims data are collected for the purpose of
      payment.

PMID- 22857540
TI  - Validation of the Traumatic Sexualization Survey for use with heterosexual men.
AB  - Two studies were conducted to validate the traumatic sexualization survey (TSS)
      for use with heterosexual men. In study 1, an online sample of men completed the
      TSS and measures used to examine convergent and divergent validity. An
      exploratory factor analysis revealed that the TSS had a similar factor structure
      in men as previously found in women. The TSS demonstrated adequate reliability
      and validity with men. In study 2, male sexually transmitted disease clinic
      patients completed the TSS and a measure of child maltreatment. Men with a child
      sexual abuse (CSA) history reported higher levels of traumatic sexualization than
      men with a history of only physical abuse or no abuse, providing some preliminary
      evidence of construct validity. The TSS appears to be an adequate measure of
      maladaptive attitudes that have been conceptually linked to CSA impact in men.

PMID- 22857598
TI  - ArfA recruits release factor 2 to rescue stalled ribosomes by peptidyl-tRNA
      hydrolysis in Escherichia coli.
AB  - The ribosomes stalled at the end of non-stop mRNAs must be rescued for productive
      cycles of cellular protein synthesis. Escherichia coli possesses at least three
      independent mechanisms that resolve non-productive translation complexes (NTCs).
      While tmRNA (SsrA) mediates trans-translation to terminate translation, ArfA
      (YhdL) and ArfB (YaeJ) induce hydrolysis of ribosome-tethered peptidyl-tRNAs.
      ArfB is a paralogue of the release factors (RFs) and directly catalyses the
      peptidyl-tRNA hydrolysis within NTCs. In contrast, the mechanism of the ArfA
      action had remained obscure beyond its ability to bind to the ribosome. Here, we
      characterized the ArfA pathway of NTC resolution in vitro and identified RF2 as a
      factor that cooperates with ArfA to hydrolyse peptidyl-tRNAs located in the P
      site of the stalled ribosome. This reaction required the GGQ (Gly-Gly-Gln)
      hydrolysis motif, but not the SPF (Ser-Pro-Phe) codon-recognition sequence, of
      RF2 and was stimulated by tRNAs. From these results we suggest that ArfA binds to
      the vacant A-site of the stalled ribosome with possible aid from association with
      a tRNA, and then recruits RF2, which hydrolyses peptidyl-tRNA in a GGQ motif
      dependent but codon-independent manner. In support of this model, the ArfA-RF2
      pathway did not act on the SecM-arrested ribosome, which contains an aminoacyl
      tRNA in the A-site.

PMID- 22857597
TI  - Serum microRNAs as biomarkers for recurrence in melanoma.
AB  - BACKGROUND: Identification of melanoma patients at high risk for recurrence and
      monitoring for recurrence are critical for informed management decisions. We
      hypothesized that serum microRNAs (miRNAs) could provide prognostic information
      at the time of diagnosis unaccounted for by the current staging system and could
      be useful in detecting recurrence after resection. METHODS: We screened 355
      miRNAs in sera from 80 melanoma patients at primary diagnosis (discovery cohort)
      using a unique quantitative reverse transcription-PCR (qRT-PCR) panel. Cox
      proportional hazard models and Kaplan-Meier recurrence-free survival (RFS) curves
      were used to identify a miRNA signature with prognostic potential adjusting for
      stage. We then tested the miRNA signature in an independent cohort of 50 primary
      melanoma patients (validation cohort). Logistic regression analysis was performed
      to determine if the miRNA signature can determine risk of recurrence in both
      cohorts. Selected miRNAs were measured longitudinally in subsets of patients pre
      /post-operatively and pre-/post-recurrence. RESULTS: A signature of 5 miRNAs
      successfully classified melanoma patients into high and low recurrence risk
      groups with significant separation of RFS in both discovery and validation
      cohorts (p = 0.0036, p = 0.0093, respectively). Significant separation of RFS was
      maintained when a logistic model containing the same signature set was used to
      predict recurrence risk in both discovery and validation cohorts (p < 0.0001, p =
      0.033, respectively). Longitudinal expression of 4 miRNAs in a subset of patients
      was dynamic, suggesting miRNAs can be associated with tumor burden. CONCLUSION:
      Our data demonstrate that serum miRNAs can improve accuracy in identifying
      primary melanoma patients with high recurrence risk and in monitoring melanoma
      tumor burden over time.

PMID- 22857599
TI  - Comparison of three generations of ActiGraphTM activity monitors in children and
      adolescents.
AB  - In this study, we evaluated agreement among three generations of ActiGraphTM
      accelerometers in children and adolescents. Twenty-nine participants (mean age =
      14.2 +/- 3.0 years) completed two laboratory-based activity sessions, each
      lasting 60 min. During each session, participants concurrently wore three
      different models of the ActiGraphTM accelerometers (GT1M, GT3X, GT3X+). Agreement
      among the three models for vertical axis counts, vector magnitude counts, and
      time spent in moderate-to-vigorous physical exercise (MVPA) was evaluated by
      calculating intraclass correlation coefficients and Bland-Altman plots. The
      intraclass correlation coefficient for total vertical axis counts, total vector
      magnitude counts, and estimated MVPA was 0.994 (95% CI = 0.989-0.996), 0.981 (95%
      CI = 0.969-0.989), and 0.996 (95% CI = 0.989-0.998), respectively. Inter-monitor
      differences for total vertical axis and vector magnitude counts ranged from 0.3%
      to 1.5%, while inter-monitor differences for estimated MVPA were equal to or
      close to zero. On the basis of these findings, we conclude that there is strong
      agreement between the GT1M, GT3X, and GT3X+ activity monitors, thus making it
      acceptable for researchers and practitioners to use different ActiGraphTM models
      within a given study.

PMID- 22857600
TI  - Infant nutrition in the first seven days of life in rural northern Ghana.
AB  - BACKGROUND: Good nutrition is essential for increasing survival rates of infants.
      This study explored infant feeding practices in a resource-poor setting and
      assessed implications for future interventions focused on improving newborn
      health. METHODS: The study took place in the Kassena-Nankana District of the
      Upper East Region of northern Ghana. In-depth interviews were conducted with 35
      women with newborn infants, 8 traditional birth attendants and local healers, and
      16 community leaders. An additional 18 focus group discussions were conducted
      with household heads, compound heads and grandmothers. All interviews and
      discussions were audio taped, transcribed verbatim and analyzed using NVivo 9.0.
      RESULTS: Community members are knowledgeable about the importance of
      breastfeeding, and most women with newborn infants do attempt to breastfeed.
      However, data suggest that traditional practices related to breastfeeding and
      infant nutrition continue, despite knowledge of clinical guidelines. Such
      traditional practices include feeding newborn infants water, gripe water, local
      herbs, or traditionally meaningful foods such as water mixed with the flour of
      guinea corn (yara'na). In this region in Ghana, there are significant cultural
      traditions associated with breastfeeding. For example, colostrum from first-time
      mothers is often tested for bitterness by putting ants in it - a process that
      leads to a delay in initiating breastfeeding. Our data also indicate that
      grandmothers - typically the mother-in-laws - wield enormous power in these
      communities, and their desires significantly influence breastfeeding initiation,
      exclusivity, and maintenance. CONCLUSION: Prelacteal feeding is still common in
      rural Ghana despite demonstrating high knowledge of appropriate feeding
      practices. Future interventions that focus on grandmothers and religious leaders
      are likely to prove valuable in changing community attitudes, beliefs, and
      practices with regard to infant nutrition.

PMID- 22857601
TI  - Noncovalent organocatalytic synthesis of enantioenriched terminal aziridines with
      a quaternary stereogenic center.
AB  - A high-yielding and enantioselective access to novel N-Boc terminal aziridines,
      bearing a quaternary stereogenic center, has been developed via an aza-Michael
      initiated ring-closure (aza-MIRC) reaction of alpha-acyl acrylates with an N
      tosyloxy tert-butyl carbamate catalyzed by a chiral amino thiourea. The
      feasibility of the aziridine regioselective ring-opening to valuable alpha,alpha
      disubstituted alpha-amino acid esters has been demonstrated.

PMID- 22857602
TI  - Socio-economic disparities in the consumption of vegetables, fruit and energy
      dense foods: the role of motive priorities.
AB  - OBJECTIVE: A low socio-economic status (SES) is related to less healthy dietary
      habits, but the reasons for this remain unclear. We examined whether the absolute
      or relative importance of various food choice motives contributed to SES
      disparities in vegetable/fruit and energy-dense food intake. DESIGN: We analysed
      cross-sectional data from the FINRISK Study 2007 by means of structural equation
      modelling and used a shortened version of the Food Choice Questionnaire to assess
      the absolute importance of health, pleasure, convenience, price, familiarity and
      ethicality motives. We calculated the relative importance of each motive by
      dividing the participant's rating of it by his/her mean score on all motives.
      Dietary intake was measured with an FFQ. SETTING: A population-based survey in
      Finland. SUBJECTS: Men (n 1691) and women (n 2059) aged 25-64 years. RESULTS:
      Higher education and income were related to a greater vegetable/fruit intake
      (beta = 0.12, P < 0.001), while education was associated negatively with the
      consumption of energy-dense foods (beta = -0.09, P < 0.001). Socio-economically
      disadvantaged individuals considered price and/or familiarity more important in
      their food choices in both absolute and relative terms. A higher income was
      related to a greater relative importance of health considerations. Relative
      motives were more strongly associated with vegetable/fruit and energy-dense food
      consumption than absolute motives and the relative importance of price,
      familiarity and health partly mediated the effects of the SES indicators on the
      consumption of these food items. CONCLUSIONS: Individual priorities in food
      choice motives, rather than the absolute importance of single motives, play a
      role in producing SES disparities in diet.

PMID- 22857603
TI  - Understanding the photomagnetic behavior in copper octacyanomolybdates.
AB  - The mechanism of photomagnetism in copper octacyanomolybdate molecules is
      currently under debate. Contrary to the general belief that the photomagnetic
      transition occurs only due to a photoinduced electron transfer from the
      molybdenum to the copper atom, recent X-ray magnetic dichroic (XMCD) data clearly
      indicate that this phenomenon is associated at low temperature to a local low
      spin-high-spin transition on the molybdenum atom. In this article we provide
      theoretical justification for these experimental facts. We show the first
      simulation of X-ray absorption (XAS) and magnetic circular dichroism (XMCD)
      spectra at the L(2,3) edges of molybdenum from the joint perspective of density
      functional theory (DFT) calculations and ligand field multiplet (LFM) theory. The
      description of electronic interactions seems mandatory for reproducing the
      photomagnetic state.

PMID- 22857604
TI  - Health performance of individuals within the Campbell paradigm.
AB  - In this paper, we developed a comprehensive health performance measure that
      formally links individual health attitudes with the likelihood of engaging in a
      wide variety of health-related behaviours from various domains such as
      sustenance, hygiene, and physical exercise. Within what Kaiser, Byrka, and Hartig
      (2010) call the Campbell paradigm, we equated general health attitude with what a
      person does to retain or promote his or her health. Thus, health behaviours, on
      one hand, were expected to form a homogeneous, transitively ordered class of
      behaviours. On the other hand, the very behavioural class was in turn thought to
      be the basis from which an individual's health attitude could be directly
      assessed. A sample of 391 adults provided us with survey data containing
      different sets of health behaviours as well as variables and personality measures
      that had been corroborated as health-behaviour relevant in previous research. We
      found that self-reports of 50 behaviours and expressions of appreciation for 20
      of these behaviours from various domains formed a transitively ordered class of
      activities. In contrast to the conventional view in health psychology, in which
      attitudes are regarded as a psychological cause behind individual behaviour, and
      in contrast to conventional findings in health psychology, where behaviours
      appear to fall into numerous sets of more or less distinct domains of health
      enhancing activities (e.g., exercising or avoiding risks), our findings speak of
      the psychological and formal unity of health behaviour. Inevitably, attitude
      measures grounded in the Campbell paradigm gauge individual attitudes, and just
      as much, they measure the health performance of individuals. 

PMID- 22857605
TI  - Risk factors for surgical site infection following caesarean section in England:
      results from a multicentre cohort study.
AB  - OBJECTIVE: To assess the frequency and risk factors for surgical site infection
      following caesarean section. DESIGN: Prospective multicentre cohort study.
      SETTING: Fourteen NHS hospitals in England, April to September 2009. POPULATION:
      Women who underwent caesarean section at participating hospitals during
      designated study periods. METHODS: Infections that met standard case definitions
      were identified through active follow up by healthcare staff during the hospital
      stay, on return to hospital, during midwife home visits and through self
      completed patient questionnaires. MAIN OUTCOME MEASURE: Surgical site infection
      within 30 days of operation. RESULTS: Altogether, 9.6% (394/4107) of women in the
      study developed a postsurgical infection following caesarean section with 0.6%
      (23/4107) readmitted for treatment of the infection. Being overweight (body mass
      index [BMI] 25-30 kg/m(2) odds ratio [OR] 1.6, 95% confidence interval [95% CI]
      1.2-2.2) or obese (BMI 30-35 kg/m(2) OR 2.4, 95% CI 1.7-3.4; BMI > 35 kg/m(2) OR
      3.7, 95% CI 2.6-5.2) were major independent risk factors for infection (compared
      with BMI 18.5-25 kg/m(2)). There was a suggestion that younger women, and
      operations performed by associate specialist and staff grade surgeons had a
      greater odds of developing surgical site infection with OR 1.9, 95% CI 1.1-3.4
      (<20 years versus 25-30 years), and OR 1.6, 95% CI 1.0-2.4 (versus consultants),
      respectively. CONCLUSIONS: This study identified high rates of postsurgical
      infection following caesarean section. Given the number of women delivering by
      caesarean section in the UK, substantial costs will be incurred as a result of
      these infections. Prevention of these infections should be a clinical and public
      health priority.

PMID- 22857606
TI  - Communicating food safety, authenticity and consumer choice. Field experiences.
AB  - The paper reviews patented and non-patented technologies, methods and solutions
      in the area of food traceability. It pays special attention to the communication
      of food safety, authenticity and consumer choice. Twenty eight recent patents are
      reviewed in the areas of (secure) identification, product freshness indicators,
      meat traceability, (secure) transport of information along the supply chain,
      country/region/place of origin, automated authentication, supply chain management
      systems, consumer interaction systems. In addition, solutions and pilot projects
      are described in the areas of Halal traceability, traceability of bird's nests,
      cold chain management, general food traceability and other areas.

PMID- 22857607
TI  - Nonviral gene delivery vectors use syndecan-dependent transport mechanisms in
      filopodia to reach the cell surface.
AB  - Lipoplexes and polyplexes, that is, assemblies of cationic lipids and polymers
      with nucleic acids, respectively, are popular nanocarriers for delivery of genes
      or siRNA into cells for therapeutic or cell biological purposes. Although
      endocytosis represents a major mechanism for their cellular entry, very little is
      known about parameters that govern early events in the initial interaction of
      such delivery devices with the cell surface. Here, we demonstrate that prior to
      entry, poly- and lipoplexes are captured by thin, actin-rich filopodial
      extensions, protruding from the cell surface. Subsequent additional recruitment
      and local clustering of filopodia-localized syndecans, presumably driven by
      multivalent interactions with the polycationic nanocarriers, appear instrumental
      in their processing to the cell body. Detailed microscopic analyses reveal that
      the latter relies on either directional surfing along or retraction of the
      filopodia. By interfering with actin polymerization or inhibiting the motor
      protein myosin II, localized at the base of filopodia, our data reveal that the
      binding of the nanocarriers to and subsequent clustering of syndecans initiates
      actin retrograde flow, which moves the syndecan-bound nanocarriers to the cell
      body. At the present experimental conditions, inhibition of this process inhibits
      nanocarrier-mediated transfection by 50-90%. The present findings add novel
      insight to our understanding of the mechanism of nanocarrier-cell surface
      interaction, which may be instrumental in further improving delivery efficiency.
      In addition, the current experimental approach may also be of relevance to
      improving our understanding of cellular infection by viruses and pathogenic
      bacteria, given a striking parallel in filopodia-mediated processing of these
      infectious particles and nanocarriers.

PMID- 22857608
TI  - Theoretical study on steric effects of DNA phosphorothioation: B-helical
      destabilization in Rp-phosphorothioated DNA.
AB  - Phosphorothioation, with sulfur replacing a nonbridging oxygen of phosphate, has
      surfaced in bacterial DNA electrophoresis. To understand structural
      characteristics of the thio-substituted DNA, we have investigated the correlation
      between the relative energy of phosphate/phosphorothioate linkage and the
      backbone torsions. The relative energies (R.E.) computed by the quantum
      mechanical method, the PBE1PBE(CPCM, solvent=water)//PBE1PBE/6-31+G(2df) level of
      theory, were used to construct energy-scoring functions against backbone torsion
      variables, resulting in the squared correlation coefficients r(2) of 0.90-0.95.
      Then, the DNA energy alteration by phosphorothioation is estimated with the
      relative energy difference (DeltaR.E.) between phosphate and phosphorothioate of
      the phosphate linkages in the DNA crystallographic database (NDB). As a result,
      Rp-phosphorothioation shifts the relative energy of B-helical structures by 2.7
      +/- 3.4 kcal/mol, destabilizing about 95% linkages, while Sp-phosphorothioation
      by -1.4 +/- 2.4 kcal/mol, stabilizing over 84% linkages in the data sets. The B
      helical destabilization is likely caused by the steric effect between the sulfur
      atom of Rp-phosphorothioate and the neighboring C-H groups of deoxyribose on the
      groove wall in B-helix. The unfavorable interaction may be magnified by the
      increasing rigidness of P-O-involving backbone torsions alpha and zeta upon the
      nonbridging phosphorothioations. Since B-helix is the most prevalent DNA double
      helical structure and Rp-phosphorothioation is the exclusive configuration in
      bacteria thio-DNA found to date, the observed stereospecificity-destabilization
      correlation may reflect a structure-function relationship of biological DNA
      phosphorothiation.

PMID- 22857609
TI  - Profiling the clinical presentation of diagnostic characteristics of a sample of
      symptomatic TMD patients.
AB  - BACKGROUND: Temporomandibular disorder (TMD) patients might present a number of
      concurrent clinical diagnoses that may be clustered according to their
      similarity. Profiling patients' clinical presentations can be useful for better
      understanding the behavior of TMD and for providing appropriate treatment
      planning. The aim of this study was to simultaneously classify symptomatic
      patients diagnosed with a variety of subtypes of TMD into homogenous groups based
      on their clinical presentation and occurrence of comorbidities. METHODS: Clinical
      records of 357 consecutive TMD patients seeking treatment in a private
      specialized clinic were included in the study sample. Patients presenting
      multiple subtypes of TMD diagnosed simultaneously were categorized according to
      the AAOP criteria. Descriptive statistics and two-step cluster analysis were used
      to characterize the clinical presentation of these patients based on the primary
      and secondary clinical diagnoses. RESULTS: The most common diagnoses were
      localized masticatory muscle pain (n = 125) and disc displacement without
      reduction (n = 104). Comorbidity was identified in 288 patients. The automatic
      selection of an optimal number of clusters included 100% of cases, generating an
      initial 6-cluster solution and a final 4-cluster solution. The interpretation of
      within-group ranking of the importance of variables in the clustering solutions
      resulted in the following characterization of clusters: chronic facial pain (n =
      36), acute muscle pain (n = 125), acute articular pain (n = 75) and chronic
      articular impairment (n = 121). CONCLUSION: Subgroups of acute and chronic TMD
      patients seeking treatment can be identified using clustering methods to provide
      a better understanding of the clinical presentation of TMD when multiple
      diagnosis are present. Classifying patients into identifiable symptomatic
      profiles would help clinicians to estimate how common a disorder is within a
      population of TMD patients and understand the probability of certain pattern of
      clinical complaints.

PMID- 22857611
TI  - Giant cystic meconium peritonitis presenting in a neonate with classic
      radiographic eggshell calcifications and treated with an elective surgical
      approach: a case report.
AB  - INTRODUCTION: Giant cystic meconium peritonitis is relatively rare. Patients
      often present with nonspecific physical findings such as distension and emesis.
      Plain abdominal films remain invaluable for identifying the characteristic
      calcifications seen with a meconium pseudocyst, and large eggshell calcifications
      are pathognomonic for the giant cystic subtype. CASE PRESENTATION: We present
      classic plain X-ray findings and an intraoperative image of a premature low birth
      weight two-day-old Hispanic male baby treated for giant cystic meconium
      peritonitis with a staged procedure involving peritoneal drainage, ostomy
      creation and closure. CONCLUSION: Pediatric surgeons have a range of potential
      therapeutic approaches for giant cystic meconium peritonitis. A delay of
      definitive surgical management in the setting of massive abdominal soiling is a
      safe and acceptable strategy if adequate temporizing drainage is performed in the
      early perinatal period.

PMID- 22857610
TI  - The receptor like kinase at Rhg1-a/Rfs2 caused pleiotropic resistance to sudden
      death syndrome and soybean cyst nematode as a transgene by altering signaling
      responses.
AB  - BACKGROUND: Soybean (Glycine max (L. Merr.)) resistance to any population of
      Heterodera glycines (I.), or Fusarium virguliforme (Akoi, O'Donnell, Homma &
      Lattanzi) required a functional allele at Rhg1/Rfs2. H. glycines, the soybean
      cyst nematode (SCN) was an ancient, endemic, pest of soybean whereas F.
      virguliforme causal agent of sudden death syndrome (SDS), was a recent, regional,
      pest. This study examined the role of a receptor like kinase (RLK) GmRLK18-1
      (gene model Glyma_18_02680 at 1,071 kbp on chromosome 18 of the genome sequence)
      within the Rhg1/Rfs2 locus in causing resistance to SCN and SDS. RESULTS: A BAC
      (B73p06) encompassing the Rhg1/Rfs2 locus was sequenced from a resistant cultivar
      and compared to the sequences of two susceptible cultivars from which 800 SNPs
      were found. Sequence alignments inferred that the resistance allele was an
      introgressed region of about 59 kbp at the center of which the GmRLK18-1 was the
      most polymorphic gene and encoded protein. Analyses were made of plants that were
      either heterozygous at, or transgenic (and so hemizygous at a new location) with,
      the resistance allele of GmRLK18-1. Those plants infested with either H. glycines
      or F. virguliforme showed that the allele for resistance was dominant. In the
      absence of Rhg4 the GmRLK18-1 was sufficient to confer nearly complete resistance
      to both root and leaf symptoms of SDS caused by F. virguliforme and provided
      partial resistance to three different populations of nematodes (mature female
      cysts were reduced by 30-50%). In the presence of Rhg4 the plants with the
      transgene were nearly classed as fully resistant to SCN (females reduced to 11%
      of the susceptible control) as well as SDS. A reduction in the rate of early
      seedling root development was also shown to be caused by the resistance allele of
      the GmRLK18-1. Field trials of transgenic plants showed an increase in foliar
      susceptibility to insect herbivory. CONCLUSIONS: The inference that soybean has
      adapted part of an existing pathogen recognition and defense cascade (H.glycines;
      SCN and insect herbivory) to a new pathogen (F. virguliforme; SDS) has broad
      implications for crop improvement. Stable resistance to many pathogens might be
      achieved by manipulation the genes encoding a small number of pathogen
      recognition proteins.

PMID- 22857613
TI  - Control of archaellation in Sulfolobus acidocaldarius: unravelling of the
      regulation of surface structure biosynthesis in Archaea begins.
AB  - Archaea have a variety of surface appendages including archaella (archaeal
      flagella), pili, hami and cannulae. While expected to be energetically expensive
      to express, studies focused on the regulation of such structures are nevertheless
      lacking. In the current issue of Molecular Microbiology, Reimann et al. (2012)
      identified a two-partner system called ArnA and ArnB in Sulfolobus acidocaldarius
      that interact strongly with each other and are repressors of archaella expression
      while also having an enhancing effect on the appearance of type IV pili. ArnA is
      a forkhead-associated domain-containing protein while ArnB is a von Willebrand
      domain-containing protein. Both proteins can be phosphorylated in vitro by S.
      acidocaldarius protein kinases. The repression of archaella expression is
      dependent on dephosphorylation of the Arn proteins. Deletions of arnA or arnB
      resulted in increased levels of archaella operon proteins and cells that were
      hypermotile due to increased archaellation. Direct effects of ArnA/ArnB on
      transcription from fla promoters were demonstrated using arnA and arnB deletion
      strains but only a modest increase in transcription was demonstrated in each
      mutant suggesting that the repression effect observed may be due to protein
      protein interactions. This paper represents a significant step forward in our
      understanding of archaeal surface structure biogenesis.

PMID- 22857614
TI  - Pyrophosphate complexation of tin(II) in aqueous solutions as applied in
      electrolytes for the deposition of tin and tin alloys such as white bronze.
AB  - Electrodeposition of tin and tin alloys from electrolytes containing tin(II) and
      pyrophosphates is an important process in metal finishing, but the nature of the
      tin pyrophosphate complexes present in these solutions in various pH regions has
      remained unknown. Through solubility and pH studies, IR and (31)P and (119)Sn NMR
      spectroscopic investigations of solutions obtained by dissolving Sn(2)P(2)O(7) in
      equimolar quantities of either Na(4)P(2)O(7).10H(2)O or K(4)P(2)O(7) the
      formation of anionic 1:1 complexes {[Sn(P(2)O(7))]}(n)(2n-) has now been verified
      and the molecular structures of the monomer (n = 1) and the dimer (n = 2) have
      been calculated by density functional theory (DFT) methods. Whereas the alkali
      pyrophosphates Na/K(4)P(2)O(7) give strongly alkaline aqueous solutions (pH ~13),
      because of partial protonation of the [P(2)O(7)](4-) anion, the [Sn(P(2)O(7))](2
      ) anion is not protonated and the solutions of Na/K(2)[Sn(P(2)O(7))] are almost
      neutral (pH ~8). The monomeric dianion appears to have a ground state with C(2v)
      symmetry with the Sn atom in a square pyramidal coordination and the lone pair of
      electrons in the apical position, while the dimer approaches C(2) symmetry with
      the Sn atoms in a rhombic pyramidal coordination, also with a sterically active
      lone pair. A comparison of experimental and calculated IR details favors the
      monomer as the most abundant species in solution. With an excess of
      pyrophosphate, 3:2 and 2:1 complexes (P(2)O(7)):(Sn) are first formed, which, in
      the presence of more pyrophosphate, undergo rapid ligand exchange on the NMR time
      scale. The structure of the 2:1 complex [Sn(P(2)O(7))(2)](6-) was calculated to
      have a pyramidal complexation by two 1,5-chelating pyrophosphate ligands.
      Neutralization of these alkaline solutions by sulfuric or sulfonic acids
      (H(2)SO(4), MeSO(3)H), as also practiced in electroplating, appears to afford the
      tin(II) hydrogen pyrophosphates [Sn(P(2)O(7)H)](-) and [Sn(H(2)P(2)O(7))](0). The
      molecular structures of the mononuclear model units have also been calculated and
      were shown to have an unsymmetrical complexation and to feature trigonal
      pyramidal (pseudotetrahedral) coordination. NMR observations have shown that,
      contrary to the results obtained for Sn(II) compounds, Sn(IV) as present in
      K(2)SnO(3) or its hydrated form (K(2)Sn(OH)(6)) does not form a pyrophosphate
      complex in aqueous solution near pH 7. There is also no interference of sulfite.

PMID- 22857612
TI  - Resveratrol inhibits inflammation induced by heat-killed Listeria monocytogenes.
AB  - Resveratrol is a polyphenolic compound in red wine that has antioxidant and
      cardioprotective effects in animal models. Listeria monocytogenes is a pathogen
      that mainly affects immunocompromised individuals and is initially detected at
      the cell surface or in phagosomes by toll-like receptor 2. Many antioxidants also
      exert anti-inflammatory activities; therefore, we evaluated the anti-inflammatory
      properties of resveratrol by studying the various inflammatory responses induced
      by heat-killed L. monocytogenes (HKLM). Resveratrol strongly blocked HKLM-induced
      NADPH oxidase-1 mRNA and reactive oxygen species production by macrophages.
      Resveratrol also suppressed monocyte chemotactic protein-1 expression,
      cyclooxygenase-2 expression, prostaglandin production, inducible nitric oxide
      (NO) synthase expression, and NO production induced by HKLM. We investigated the
      signaling pathway involved in the resveratrol effect. HKLM stimulated glycogen
      synthase kinase 3beta (GSK3beta) and extracellular signal-regulated kinase 1/2
      (ERK1/2) phosphorylation. The involvement of GSK3beta and ERK1/2 was tested using
      inhibitors. While the GSK3beta inhibitor LiCl potentiated the effect of HKLM, the
      MEK inhibitor U0126 blocked these responses. Additionally, pretreatment with
      resveratrol blocked phosphorylation of both kinases induced by HKLM. These
      results suggest that HKLM is strong inducer of inflammatory mediators, and that
      the inhibitory effect of resveratrol may be mediated by the GSK3beta and ERK1/2
      pathways.

PMID- 22857615
TI  - Some aspects of quality management in deep regional hyperthermia.
AB  - The hyperthermia effect is based on its thermal influence on tumours. Therefore a
      controlled heating of the tumours must be achieved. In order to guarantee this,
      two points must be fulfilled at least: First, the hyperthermia equipment must
      have the necessary power and steering capability. Second, the distribution of the
      'hyperthermic drug', the heat, has to be measured and controlled over the whole
      treatment time. To reach this aim both a sophisticated technique and a staff
      trained in hyperthermia are required. In treating patients such as those with
      cervical cancer, the volume to be exposed and the dosage must be clarified. This
      means that very special technical and medical conditions must be fulfilled in
      hyperthermia. To reach and maintain a certain level of quality, hyperthermia is
      embedded in a framework of procedures. These procedures are defined in the
      modules of quality management. Therefore quality management must contain specific
      guidelines for each application, i.e. coordinated standards have to be defined.
      When adapting these standards in hyperthermia, comparable and comprehensible
      results of the treatment are guaranteed. Furthermore, an analysis of the
      treatments under a scientific point of view will be possible and finally result
      in improvements of this method.

PMID- 22857616
TI  - Fixed-point drift and hysteresis in frequency-scaled unimanual coordination.
AB  - Research on human rhythmic coordination has shown that the in-phase and antiphase
      coordination modes are typically stable and that the coordination of asymmetric
      effectors frequently exhibits fixed-point drift. The author extended research on
      symmetry breaking in coordination dynamics by examining a frequency-scaled
      unimanual pronation-supination task. The results showed symmetry breaking and
      fixed-point drift, with the radioulnar joint increasingly more phase advanced
      than the shoulder with increments in movement frequency. Hysteresis was also
      observed, as the relative phase patterns produced at 3 of the 4 movement
      frequencies were lower in the upward frequency scaling direction than in the
      downward direction. These results showed that the dynamic properties of symmetry
      breaking and fixed-point drift in unimanual pronation-supination movements were
      consistent with prior research and modeling. The hysteresis effect was explained
      as potentially being due to the control structures that organize this redundant
      coordination task.

PMID- 22857643
TI  - 10 must-dos for successful breastfeeding support groups.

PMID- 22857644
TI  - An association between hOGG1 Ser326Cys polymorphism and the risk of bladder
      cancer in non-smokers: a meta-analysis.
AB  - BACKGROUND: Bladder cancer results from complex interactions between many genetic
      and environment factors. The polymorphism Ser326Cys in hOGG1 gene has been
      reported to be associated with bladder cancer in some studies, though the results
      remain inconclusive. To explore this relationship of hOGG1 polymorphism and the
      susceptibility for bladder cancer and the impact of smoking exposures, a
      cumulative meta-analysis was performed in this study. METHODS: We extracted the
      data from the Pubmed database up to January 9, 2012 using the search phrases
      "hOGG1, Ser326Cys polymorphism and bladder cancer". Seven case-control studies
      were identified, including 2474 patients and 2408 controls. Four of them provided
      the analysis of smoking effects, with 1372 smokers and 947 non-smokers. The odds
      ratios (ORs) and associated 95 % confidence intervals (CIs) were calculated using
      fixed- or random- effects models. RESULTS: Regarding the overall association
      between the hOGG1 326Cys allele and bladder cancer risk, the meta-analysis did
      not reveal a significant effect in the additive model (OR: 1.06, 95 % CI: 0.96
      1.26; p = 0.49), the recessive genetic model (OR: 1.05, 95 % CI: 0.65-1.70; p =
      0.85) or the dominant genetic model (OR: 1.07, 95 % CI: 0.87-1.32; p = 0.53).
      Similarly, no significant relationship was observed in the stratified analysis by
      ethnicity, study design and Hardy-Weinberg equilibrium (all p > 0.05). In the non
      smokers, however, hOGG1 326Cys allele significantly increased the risk for
      bladder cancer and the ORs in the additive model, homozygote contrast and
      recessive genetic model were 1.59 (p = 0.02), 2.53(p = 0.003) and 2.41(p =
      0.0005), respectively. Nevertheless, in the smoker subgroup, similar findings
      could not be found in all genetic models (all p > 0.05). CONCLUSIONS: The
      association between the hOGG1 326Cys allele and bladder cancer was significant in
      non-smoker population, while was non-detectable in common or smoker populations.
      This meta-analysis suggests that the hOGG1 Ser326Cys polymorphism may be a risk
      factor for bladder cancer without exposure to smoking. Further functional studies
      are needed to elucidate the gene polymorphism-bladder cancer relationship and
      gene-environment interactions.

PMID- 22857645
TI  - Commentary: True blood--changes in blood management in pediatric deformity
      surgery.

PMID- 22857646
TI  - Commentary: Interspinous devices, spondylolisthesis, and spinous process-related
      complications.

PMID- 22857647
TI  - Letter to the editor regarding: "Early versus delayed decompression for traumatic
      cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord
      Injury Study (STASCIS)".

PMID- 22857650
TI  - Association of fish and n-3 fatty acid intake with the risk of type 2 diabetes: a
      meta-analysis of prospective studies.
AB  - Results from observational studies on the association of fish and n-3 fatty acid
      consumption with type 2 diabetes mellitus (T2DM) risk are conflicting. Hence, a
      meta-analysis was performed to investigate this association from cohort studies.
      A comprehensive search was then conducted to identify cohort studies on the
      association of fish and/or n-3 fatty acid intake with T2DM risk. In the highest
      v. lowest categorical analyses, the fixed or random-effect model was selected
      based on the homogeneity test among studies. Linear and non-linear dose-response
      relationships were also assessed by univariate and bivariate random-effect meta
      regression with restricted maximum likelihood estimation. In the highest v.
      lowest categorical analyses, the pooled relative risk (RR) of T2DM for intake of
      fish and n-3 fatty acid was 1.146 (95 % CI 0.975, 1.346) and 1.076 (95 % CI
      0.955, 1.213), respectively. In the linear dose-response relationship, the pooled
      RR for an increment of one time (about 105 g)/week of fish intake (four
      times/month) and of 0.1 g/d of n-3 fatty acid intake was 1.042 (95 % CI 1.026,
      1.058) and 1.057 (95 % CI 1.042, 1.073), respectively. The significant non-linear
      dose-response associations of fish and n-3 fatty acid intake with T2DM risk were
      not observed. The present evidence from observational studies suggests that the
      intake of both fish and n-3 fatty acids might be weakly positively associated
      with the T2DM risk. Further studies are needed to confirm these results.

PMID- 22857651
TI  - Rhodium-catalyzed three-component reaction between silylacetylene and two ketenes
      leading to 1,3-enynes bearing a carboxylic ester group via double insertion of
      ketenes.
AB  - The first cross-reaction between a terminal silylacetylene and two ketene
      molecules leading to 1,3-enynes bearing a carboxylic ester group via double
      insertion of ketenes is achieved using a cationic rhodium complex catalyst. This
      reaction is applicable for various symmetrical and unsymmetrical ketenes with
      good stereoselectivities.

PMID- 22857649
TI  - Diagnostic and prognostic value of cardiovascular magnetic resonance in non
      ischaemic cardiomyopathies.
AB  - Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool
      which in a single scan setting can assess ventricular volumes and function,
      myocardial fibrosis, iron loading, flow quantification, tissue characterisation
      and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic
      contrast-enhanced protocols for tissue characterisation have dramatically changed
      the non-invasive work-up of patients with suspected or known cardiomyopathy.
      Although the technique initially focused on the in vivo identification of
      myocardial necrosis through the late gadolinium enhancement (LGE) technique,
      recent work highlighted the ability of CMR to provide more detailed in vivo
      tissue characterisation to help establish a differential diagnosis of the
      underlying aetiology, to exclude an ischaemic substrate and to provide important
      prognostic markers. The potential application of CMR in the clinical approach of
      a patient with suspected non-ischaemic cardiomyopathy is discussed in this
      review.

PMID- 22857653
TI  - Lipid-peptide vesicle nanoscale hybrids for triggered drug release by mild
      hyperthermia in vitro and in vivo.
AB  - The present study describes leucine zipper peptide-lipid hybrid nanoscale
      vesicles engineered by self-assembled anchoring of the amphiphilic peptide within
      the lipid bilayer. These hybrid vesicles aim to combine the advantages of
      traditional temperature-sensitive liposomes (TSL) with the dissociative,
      unfolding properties of a temperature-sensitive peptide to optimize drug release
      under mild hyperthermia, while improving in vivo drug retention. The secondary
      structure of the peptide and its thermal responsiveness after anchoring onto
      liposomes were studied with circular dichroism. In addition, the lipid-peptide
      vesicles (Lp-peptide) showed a reduction in bilayer fluidity at the inner core,
      as observed with DPH anisotropy studies, while the opposite effect was observed
      with an ANS probe, indicating peptide interactions with both the headgroup region
      and the hydrophobic core. A model drug molecule, doxorubicin, was successfully
      encapsulated in the Lp-peptide vesicles at higher than 90% efficiency following
      the remote loading, pH-gradient methodology. The release of doxorubicin from Lp
      peptide hybrids in vitro indicated superior serum stability at physiological
      temperatures compared to lysolipid-containing temperature-sensitive liposomes
      (LTSL) without affecting the overall thermo-responsive nature of the vesicles at
      42  degrees C. A similar stabilizing effect was observed in vivo after
      intravenous administration of the Lp-peptide vesicles by measuring (14)C
      doxorubicin blood kinetics that also led to increased tumor accumulation after 24
      h. We conclude that Lp-peptide hybrid vesicles present a promising new class of
      TSL that can offer previously unexplored opportunities for the development of
      clinically relevant mild hyperthermia-triggered therapeutic modalities.

PMID- 22857655
TI  - Good exams made easy: the item management system for multiple examination
      formats.
AB  - BACKGROUND: The development, implementation and evaluation of assessments require
      considerable resources and often cannot be carried out by a single
      faculty/institution. Therefore some medical faculties have founded cooperation
      projects which mainly focus on the exchange of multiple choice questions (MCQs).
      METHODS: Since these cooperation projects do not entirely support all relevant
      processes in terms of preparation, implementation and evaluation of assessment,
      in 2006 the Medical Assessment Alliance (MAA) was founded for mutual support. In
      addition to MCQs the MAA started to develop innovative assessment formats and
      facilitate content through a coordinated exchange of experiences. To support
      cooperation within this network, the web-based Item Management System (IMS) was
      developed which supports all processes of the assessment workflow as an all-in
      one working platform. RESULTS: At present, the Alliance has 28 partner faculties
      in Europe. More than 2.800 users in 750 working groups are collaborating.
      Currently 90.000 questions have been stored in the IMS. Since 2007, nearly 4.600
      examinations have been successfully conducted. CONCLUSION: This article describes
      in detail the unique features of the IMS and contrasts it with the item
      management systems of other associations.

PMID- 22857657
TI  - Lactic acidosis secondary to metformin overdose: a case report.
AB  - INTRODUCTION: Metformin is a commonly used treatment modality in type 2 diabetes
      mellitus, with a well documented side effect of lactic acidosis. In the intensive
      care setting lactate and pH levels are regularly used as a useful predictor of
      poor prognosis. In this article we highlight how high lactate levels are not an
      accurate predictor of mortality in deliberate metformin overdose. CASE
      PRESENTATION: We present the case of a 70-year-old Caucasian man who took a
      deliberate metformin overdose of unknown quantity. He had a profound lactic
      acidosis at presentation with a pH of 6.93 and a lactate level of more than
      20mmol/L. These figures would normally correspond with a mortality of more than
      80%; however, with appropriate management this patient's condition improved.
      CONCLUSION: We provide evidence that the decision to treat severe lactic acidosis
      in deliberate metformin overdose should not be based on arterial lactate and pH
      levels, as would be the case in other overdoses. We also demonstrate that
      appropriate treatment with hemodiafiltration and 8.4% sodium bicarbonate, even in
      patients with a very high lactate and low pH, can be successful.

PMID- 22857707
TI  - Experimental and computational study of a new wheel-shaped
      {[W5O21]3[(U(VI)O))2(MU-O2)]3}30- polyoxometalate.
AB  - A new wheel-shaped polyoxometalate {[W(5)O(21)](3)[(U(VI)O(2))(2)(MU
      O(2))](3)}(30-) has been synthesized and structurally characterized. The
      calculated electrostatic potential reveals the protonation of several MU-oxo
      bridges reducing the polyoxometalate total charge. A protonated structure
      computed at the density functional level of theory (DFT) is in good agreement
      with the experimental fit. This species presents a classical polyoxometalate
      electronic structure with well-defined metal and oxo bands belonging to its U/W
      and oxo/peroxo constituents, respectively. Furthermore, fragment calculations
      indicate that the electronic structures of the uranyl-peroxide and
      polyoxotugstate fragments are little affected by the nanowheel assembly.

PMID- 22857656
TI  - Jasmonate and ethylene dependent defence gene expression and suppression of
      fungal virulence factors: two essential mechanisms of Fusarium head blight
      resistance in wheat?
AB  - BACKGROUND: Fusarium head blight (FHB) caused by Fusarium species like F.
      graminearum is a devastating disease of wheat (Triticum aestivum) worldwide.
      Mycotoxins such as deoxynivalenol produced by the fungus affect plant and animal
      health, and cause significant reductions of grain yield and quality. Resistant
      varieties are the only effective way to control this disease, but the molecular
      events leading to FHB resistance are still poorly understood. Transcriptional
      profiling was conducted for the winter wheat cultivars Dream (moderately
      resistant) and Lynx (susceptible). The gene expressions at 32 and 72 h after
      inoculation with Fusarium were used to trace possible defence mechanisms and
      associated genes. A comparative qPCR was carried out for selected genes to
      analyse the respective expression patterns in the resistant cultivars Dream and
      Sumai 3 (Chinese spring wheat). RESULTS: Among 2,169 differentially expressed
      genes, two putative main defence mechanisms were found in the FHB-resistant Dream
      cultivar. Both are defined base on their specific mode of resistance. A non
      specific mechanism was based on several defence genes probably induced by
      jasmonate and ethylene signalling, including lipid-transfer protein, thionin,
      defensin and GDSL-like lipase genes. Additionally, defence-related genes encoding
      jasmonate-regulated proteins were up-regulated in response to FHB. Another
      mechanism based on the targeted suppression of essential Fusarium virulence
      factors comprising proteases and mycotoxins was found to be an essential, induced
      defence of general relevance in wheat. Moreover, similar inductions upon fungal
      infection were frequently observed among FHB-responsive genes of both mechanisms
      in the cultivars Dream and Sumai 3. CONCLUSIONS: Especially ABC transporter, UDP
      glucosyltransferase, protease and protease inhibitor genes associated with the
      defence mechanism against fungal virulence factors are apparently active in
      different resistant genetic backgrounds, according to reports on other wheat
      cultivars and barley. This was further supported in our qPCR experiments on seven
      genes originating from this mechanism which revealed similar activities in the
      resistant cultivars Dream and Sumai 3. Finally, the combination of early-stage
      and steady-state induction was associated with resistance, while transcript
      induction generally occurred later and temporarily in the susceptible cultivars.
      The respective mechanisms are attractive for advanced studies aiming at new
      resistance and toxin management strategies.

PMID- 22857708
TI  - Snail transcription factor negatively regulates maspin tumor suppressor in human
      prostate cancer cells.
AB  - BACKGROUND: Maspin, a putative tumor suppressor that is down-regulated in breast
      and prostate cancer, has been associated with decreased cell motility. Snail
      transcription factor is a zinc finger protein that is increased in breast cancer
      and is associated with increased tumor motility and invasion by induction of
      epithelial-mesenchymal transition (EMT). We investigated the molecular mechanisms
      by which Snail increases tumor motility and invasion utilizing prostate cancer
      cells. METHODS: Expression levels were analyzed by RT-PCR and western blot
      analyses. Cell motility and invasion assays were performed, while Snail
      regulation and binding to maspin promoter was analyzed by luciferase reporter and
      chromatin immunoprecipitation (ChIP) assays. RESULTS: Snail protein expression
      was higher in different prostate cancer cells lines as compared to normal
      prostate epithelial cells, which correlated inversely with maspin expression.
      Snail overexpression in 22Rv1 prostate cancer cells inhibited maspin expression
      and led to increased migration and invasion. Knockdown of Snail in DU145 and C4-2
      cancer cells resulted in up-regulation of maspin expression, concomitant with
      decreased migration. Transfection of Snail into 22Rv1 or LNCaP cells inhibited
      maspin promoter activity, while stable knockdown of Snail in C4-2 cells increased
      promoter activity. ChIP analysis showed that Snail is recruited to the maspin
      promoter in 22Rv1 cells. CONCLUSIONS: Overall, this is the first report showing
      that Snail can negatively regulate maspin expression by directly repressing
      maspin promoter activity, leading to increased cell migration and invasion.
      Therefore, therapeutic targeting of Snail may be useful to re-induce expression
      of maspin tumor suppressor and prevent prostate cancer tumor progression.

PMID- 22857709
TI  - Characterizing genomic variation of Arabidopsis thaliana: the roles of geography
      and climate.
AB  - Arabidopsis thaliana inhabits diverse climates and exhibits varied phenology
      across its range. Although A. thaliana is an extremely well-studied model
      species, the relationship between geography, growing season climate and its
      genetic variation is poorly characterized. We used redundancy analysis (RDA) to
      quantify the association of genomic variation [214 051 single nucleotide
      polymorphisms (SNPs)] with geography and climate among 1003 accessions collected
      from 447 locations in Eurasia. We identified climate variables most correlated
      with genomic variation, which may be important selective gradients related to
      local adaptation across the species range. Climate variation among sites of
      origin explained slightly more genomic variation than geographical distance.
      Large-scale spatial gradients and early spring temperatures explained the most
      genomic variation, while growing season and summer conditions explained the most
      after controlling for spatial structure. SNP variation in Scandinavia showed the
      greatest climate structure among regions, possibly because of relatively
      consistent phenology and life history of populations in this region. Climate
      variation explained more variation among nonsynonymous SNPs than expected by
      chance, suggesting that much of the climatic structure of SNP correlations is due
      to changes in coding sequence that may underlie local adaptation.

PMID- 22857710
TI  - Butyltin compounds in liver of harbour porpoises (Phocoena phocoena) from the UK
      prior to and following the ban on the use of tributyltin in antifouling paints
      (1992-2005 & 2009).
AB  - Liver butyltin concentrations (monobutyl, dibutyl and tributyltin (TBT)) in
      harbour porpoises (n=410) have been determined during 1992-2005, and again in
      2009 following a ban on the use of tributyltin-based antifouling paints on ships.
      The aim was to assess the effectiveness of the regulation, which was implemented
      during 2003-2008. Since the ban was put in place summed butyltin concentrations
      have declined. Also, the percentage of animals in which TBT was detected has
      fallen sharply, indicating the cessation of fresh inputs. In 1992, 1993 and 1995,
      TBT was detected in 100% of samples analysed. In 2003-2005, once the
      implementation of the ban had begun, this fell to 61-72%, and in 2009, following
      the completion of the ban, had reduced to 4.3% (i.e. in only 1 of 23 samples
      analysed). Thus we conclude that the ban has proved effective in reducing TBT
      inputs to the seas from vessels.

PMID- 22857711
TI  - Ascidian introductions through the Suez Canal: The case study of an Indo-Pacific
      species.
AB  - Although marine biological invasions via the Suez Canal have been extensively
      documented, little is known about the introduction of non-indigenous ascidians
      (Chordata, Ascidiacea), a group containing particularly aggressive invasive
      species. Here, we used a multidisciplinary approach to study the introduction of
      the ascidian Herdmania momus into the Mediterranean Sea. We reviewed its taxonomy
      and global distribution, and analyzed how genetic variation is partitioned
      between sides of the Suez Canal. The taxonomic revision showed that H. momus
      currently has a wide Indo-Pacific distribution. Genetic data indicated two well
      differentiated colonization histories across the eastern Mediterranean. Our
      findings suggest that the range expansion of H. momus has been greatly
      facilitated by the combined effect of human-mediated transport and the species'
      ability to adapt to different environments. The integrative approach presented
      here is critical to attain a holistic understanding of marine biological
      invasions, especially when studying groups with a poorly resolved taxonomy.

PMID- 22857712
TI  - Therapeutic antioxidants for neurodegenerative disease.

PMID- 22857713
TI  - Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of
      tumor initiation.
AB  - Pyrrolizidine alkaloid-containing plants are widespread in the world and are
      probably the most common poisonous plants affecting livestock, wildlife, and
      humans. Pyrrolizidine alkaloids are among the first chemical carcinogens
      identified in plants. Previously, we determined that metabolism of pyrrolizidine
      alkaloids in vivo and in vitro generated a common set of DNA adducts that are
      responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously
      determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4)
      were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid.
      Because of the lack of an adequate amount of authentic standards, the structures
      of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for
      DHP-dG-4 warranted further validation. In this study, we developed an improved
      synthetic methodology for these DNA adducts, enabling their full structural
      elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA
      3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)
      dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)
      yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA
      adducts unequivocally elucidated, we conclude that cellular DNA preferentially
      binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9
      position of the necine base, rather than at the C7 position. We also determined
      that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are
      interconvertible. This study represents the first report with detailed structural
      assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid
      tumor induction on the molecular level. A mechanism of tumor initiation by
      pyrrolizidine alkaloids is consequently fully determined.

PMID- 22857714
TI  - Where can you do more: medical schools, hospitals, clinics, or community-based
      organizations?

PMID- 22857715
TI  - Do humans prefer to see their grasping points?
AB  - To grasp an object the digits need to be placed at suitable positions on its
      surface. The selection of such grasping points depends on several factors. Here
      the authors examined whether being able to see 1 of the selected grasping points
      is such a factor. Subjects grasped large cylinders or oriented blocks that would
      normally be grasped with the thumb continuously visible and the final part of the
      index finger's trajectory occluded by the object in question. An opaque screen
      that hid the thumb's usual grasping point was used to examine whether individuals
      would choose a grip that was oriented differently to maintain vision of the
      thumb's grasping point. A transparent screen was used as a control. Occluding the
      thumb's grasping point made subjects move more carefully (adopting a larger grip
      aperture) and choose a slightly different grip orientation. However, the change
      in grip orientation was much too small to keep the thumb visible. The authors
      conclude that humans do not particularly aim for visible grasping points.

PMID- 22857716
TI  - Pediatric head injuries.
AB  - Head injuries in children are common, comprising more than half of all injuries
      sustained. The mortality and morbidity associated with traumatic head injury in
      children is staggering, and the cumulative effect of such on the pediatric and
      general populations is propagated through related health care measures and
      subsequent socioeconomic burden. The majority of deaths due to trauma in children
      are caused by brain injury. This article reviews the evaluation and management of
      scalp injuries in the pediatric patient. The second portion addresses skull
      fractures, the specter of child abuse, management of acute fracture, and the
      phenomenon of growing skull fractures.

PMID- 22857717
TI  - Growth and development considerations for craniomaxillofacial surgery.
AB  - The purpose of craniomaxillofacial surgery is to improve function, occlusion,
      craniofacial balance, and aesthetics. Accurate diagnosis, assessment, and careful
      treatment planning are essential in achieving a successful outcome, and an
      understanding of the pattern of facial growth is integral in this process.
      Patients with craniofacial congenital dysmorphologies, posttraumatic asymmetries,
      or disturbances of facial balance from radiation may have functional and/or
      aesthetic issues that require treatment. Understanding the complexities of growth
      in the skull and face is a key component to appropriate treatment planning for
      these disorders. This article reviews growth and development in the craniofacial
      skeleton.

PMID- 22857718
TI  - Pediatric neck masses.
AB  - The majority of neck masses in the pediatric population are congenital or
      inflammatory in origin requiring a thorough understanding of embryology and
      anatomy of the cervical region. However, malignancy must always be ruled out as
      they represent 11%-15% of all neck masses in the pediatric population. The
      initial history and physical are of utmost important to correctly work-up and
      eventually diagnose the lesion. This article addresses many aspects of the
      workup, diagnosis and eventual proper surgical or medical management of pediatric
      neck masses.

PMID- 22857719
TI  - Sinonasal disease and orbital cellulitis in children.
AB  - Sinonasal disease is common in the pediatric population because of anatomic,
      environmental, and physiologic factors. Once paranasal sinusitis develops,
      orbital cellulitis is a concerning sequela that can result in loss of visual
      acuity and even intracranial disease. Thus, a clear history and physical
      examination in conjunction with radiographic studies are critical to a correct
      diagnosis and timely institution of treatment that may include hospitalization,
      serial ophthalmologic examinations, intravenous antibiotics, and surgery. The
      serious nature of orbital cellulitis in children cannot be overestimated; but, if
      prompt and appropriate treatment is initiated, the prognosis is excellent and
      long-term sequelae should be limited.

PMID- 22857720
TI  - Facial dermatologic lesions in children.
AB  - This article briefly reviews some of the most common skin lesions in the head and
      neck of a child. Benign "lumps and bumps" are very common in children and it is
      prudent for the pediatric maxillofacial surgeon to be familiar with their
      presentation, workup (including radiographic studies), and definitive surgical
      management. Inflammatory and infectious lesions require prompt treatment to avoid
      more serious sequelae of progressive infection and scarring.

PMID- 22857722
TI  - [Prioritization in health care 2012 - on the current status of the discussion].

PMID- 22857721
TI  - Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo
      controlled trial in healthy male subjects.
AB  - BACKGROUND: Heme arginate can induce heme oxygenase-1 to protect tissue against
      ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional
      magnetic resonance imaging measures changes in tissue oxygenation with a high
      spatial and temporal resolution. BOLD imaging was applied to test the effect of
      heme arginate on experimental ischemia reperfusion injury in the calf muscles.
      METHODS: A two period, controlled, observer blinded, crossover trial was
      performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or
      placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff.
      3 Tesla BOLD-imaging of the calf was performed and signal time courses from
      soleus, gastrocnemius and tibialis anterior muscle were available from 11
      participants for technical reasons. RESULTS: Peak reactive hyperemia signal of
      the musculature was significantly increased and occurred earlier after heme
      arginate compared to placebo (106.2 +/- 0.6% at 175 +/- 16s vs. 104.5 +/- 0.6% at
      221 +/- 19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak).
      CONCLUSIONS: A single high dose of heme arginate improves reperfusion patterns
      during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is
      applicable for the assessment of experimental ischemia reperfusion injury in
      skeletal muscle.

PMID- 22857723
TI  - [What kind of debate on prioritisation do we need for the benefit of our health
      system and society?].
AB  - The debate on prioritisation aims to generate broad consensus on the social
      distribution of health care goods. There is nothing wrong with this aim but the
      political debate around it should include a discussion whether prioritisation is
      the strategy needed to realize this goal. Obviously, prioritisation follows the
      currently prevalent logic of evaluation as a universal legitimating strategy but,
      due to its multiple and unforeseeable effects, this does not necessarily imply
      that prioritisation will deliver on its promises. Hence, the debate cannot be
      focused on the appropriate strategies of prioritisation as its proponents seem to
      intend, but must also include the social costs and potentially adversary effects
      of this strategy of rationalisation. (As supplied by publisher).

PMID- 22857724
TI  - [The national public discourse on priority setting in health care in German print
      media].
AB  - Germany's Central Ethics Committee of the Federal Chamber of Physicians (FCP) and
      other relevant national actors called for a public discourse on priority setting
      in health care. Politicians, members of a Federal Joint Committee and health
      insurance representatives, however, refused to promote or participate in the
      establishment of a public discussion. A change to that attitude only became
      apparent after former FCP President Hoppe's opening speech at the annual FCP
      assembly in Mainz in 2009. The present paper applies the Sociology of Knowledge
      Approach to Discourse, implemented through Qualitative Content Analysis and
      elements of Grounded Theory, to examine the development of the national public
      discourse in leading German print media. It creates a matrix that represents the
      discourse development between May 2009 and May 2010 and reflects central actors,
      their "communicative phenomena" and their interactions. Additionally, the matrix
      has been extended to cover the period until December 2011. Hoppe's arguments for
      priority setting in health care are faced with a wide opposition assuming
      opposing prerequisites and thus demanding alternative remedies. The lack of
      interaction between the different parties prevents any development of the
      speakers' positions. Incorrect accounts, reductions and left-outs in the media
      representation add to this effect. Consequently, the public discussion on
      priority setting is far from being an evolving rational discourse. Instead, it
      constitutes an exchange of preformed opposing positions.

PMID- 22857725
TI  - [Critical reflections on the prioritisation debate: are we setting the right
      priorities to address our prioritisation challenges?].
AB  - A personal view of a stubborn opponent of rationing: why my conscience is fine
      with refraining from rationing but not from conducting research on
      prioritisation.

PMID- 22857726
TI  - [Prioritization is actually quite a self-evident evaluation process, however it
      may not supplant the important debate about rationalization (interview by Heiner
      Raspe and Sabine Stumpf)].

PMID- 22857727
TI  - [Democratic institutional design in health care priority setting and rationing].
AB  - Decisions on priority setting and rationing in health care have both
      informational and distributional aspects, which is why they require expert
      knowledge and specialised bodies on the one hand and democratic consent on the
      other hand. The paper presents normative criteria for the evaluation and
      empirical categories for the description and comparison of respective bodies. As
      procedural decisions always have implications for resulting distributional
      decisions, the bodies charged with priority setting and rationing decisions must
      be subject to democratic institutional design. (As supplied by publisher).

PMID- 22857728
TI  - [Stakeholder participation in priority setting - a consideration of the normative
      status of quantitative and qualitative methods].
AB  - Priority setting in medicine is generally regarded as an appropriate means for
      preparing just allocation of medical resources. By involving the general public
      or affected stakeholders in priority setting, advocates hope to legitimise this
      process and increase the acceptability of future decisions on resource
      allocation. Here, we differentiate between two ideal-typical methods of
      stakeholder involvement: 1) qualitative and 2) quantitative ones. We argue that
      the level of information of participants is important to the quality of the
      outcome of participatory events. Qualitative methods aim at fostering
      deliberative discussions among well-informed stakeholders. By contrast,
      quantitative methods usually do not have the capacity to ensure or, at least,
      control the level of information that participants use to guide their decisions.
      Hence, we conclude that in the context of priority setting qualitative and
      especially deliberative methods are preferable to quantitative approaches.

PMID- 22857729
TI  - [Deliberative participation of citizens in the prioritisation debate: what is
      their contribution?].
AB  - The German debate on prioritisation in medicine is getting well under way. This
      development has raised the question of which substantial and procedural criteria
      should be used to guide fair and legitimate prioritisation. It seems to be
      obvious that in a pluralist, democratic society citizens should be involved in
      such a discussion. But which is the adequate method, and what is the potential of
      citizen participation? In this paper we compare the results of a regional
      citizens' conference on prioritisation in medicine with various European reports
      on principles and criteria for prioritisation, and thereby aim to identify the
      conference members'contributions to the German debate on prioritisation criteria.
      The results of this exemplary deliberative event can provide hints towards the
      general potential of discursive participation. (As supplied by publisher).

PMID- 22857730
TI  - [Rationing health care by thresholds for clinical benefit and its acceptance by
      the German population].
AB  - Fair rationing in publicly accessible health care has become a subject of current
      international debate. One suggestion is to cut reimbursement for any medical
      intervention below some threshold of small clinical benefit. One can further
      differentiate between thresholds of small expectable clinical benefit as such and
      thresholds of low chances for clinical success. Public acceptance of both types
      of thresholds has been tested in a population survey. Results are presented and
      discussed in this paper. (As supplied by publisher).

PMID- 22857731
TI  - [National and regional prioritisation in Swedish health care: experiences from
      cardiology].
AB  - Prioritisation of medical services in Sweden takes place on two different levels.
      On the national level, the Swedish priority guidelines ascribe priority values
      ranging from 1 (high priority) to 10 (low priority) to measures (in terms of
      condition-treatment pairs) of prevention, diagnosis, treatment and rehabilitation
      of cardiovascular diseases. In addition, this list contains interventions that
      should be avoided and those that should only be provided as part of clinical
      research projects. The government then commissions a multi-professional team
      under the supervision of the National Board of Health and Welfare
      "Socialstyelsen" with the development of corresponding guidelines. In addition to
      the scientific evidence, the priority lists incorporate ethical and economical
      aspects and are based on the so-called ethics platform consisting of human
      dignity, needs, solidarity and cost-effectiveness. At the other level of
      prioritisation there are regional projects aiming at the in- and exclusion of
      medical measures. The Swedish prioritisation process will be described using the
      example of priority lists in cardiology. (As supplied by publisher).

PMID- 22857732
TI  - [The 'Myozyme' decision of the Federal Supreme Court of Switzerland and German
      Law: a constitutional rights and health insurance law perspective].
AB  - In November 2010, the Federal Supreme Court of Switzerland dismissed a plea
      seeking reimbursement for treatment of glycogen storage disease type II - a very
      rare genetic metabolic disease also referred to as acid maltase deficiency (AMD)
      or Pompe disease -with a drug called 'Myozyme'. The Court held that the
      medication was not sufficiently effective or, alternatively, there was
      insufficient evidence for its effectiveness. The Court argued that the cost was
      out of balance with respect to the effects of the drug and concluded that it
      would be against the principle of legal equality if taxpayers were required to
      defray excessive expenses benefiting only an extremely small fraction of the
      population. Cost-effectiveness, however, cannot be accepted as a standard
      criterion governing the allocation of health insurance benefits because diversity
      of individual health must be regarded as a risk which nature has distributed
      equally among the members of the population. Therefore, it is a manifestation,
      rather than a violation, of the principle of legal equality that a public health
      insurance provider should pay for medical treatment in a particular case even if
      such treatment could not necessarily be administered to all other insured parties
      as well. At the same time, if cost-effectiveness in public health care is taken
      into account carefully, the risk of irrational resource allocation may be
      minimised. (As supplied by publisher).

PMID- 22857733
TI  - [GRADE guidelines: 3. Rating the quality of evidence (confidence in the estimates
      of effect)].
AB  - This article introduces the GRADE approach to rating the quality of evidence.
      GRADE specifies four categories (high, moderate, low, and very low) that are
      applied to a body of evidence, not to individual studies. In the context of a
      systematic review, quality reflects our confidence that the estimates of the
      effect are correct. In the context of recommendations, quality reflects our
      confidence that the effect estimates are adequate to support a particular
      recommendation. Randomised trials begin as high quality evidence, observational
      studies as low quality. "Quality" as used in GRADE means more than risk of bias
      and so may also be compromised by imprecision, inconsistency, indirectness of
      study results, and publication bias. In addition, several factors can increase
      our confidence in an estimate of effect. GRADE provides a systematic approach for
      considering and reporting each of these factors. GRADE separates the process of
      assessing quality of evidence from the process of making recommendations.
      Judgments about the strength of a recommendation depend on more than just the
      quality of evidence.

PMID- 22857734
TI  - [GRADE guidelines: 4. Rating the quality of evidence - limitations of clinical
      trials (risk of bias)].
AB  - In the GRADE approach, randomised trials start as high-quality evidence and
      observational studies as low-quality evidence, but both can be rated down if most
      of the relevant evidence comes from studies that suffer from a high risk of bias.
      Well-established limitations of randomised trials include failure to conceal
      allocation, failure to blind, loss to follow-up, and failure to appropriately
      consider the intention-to-treat principle. More recently, recognised limitations
      include stopping early for apparent benefit and selective reporting of outcomes
      according to the results. Key limitations of observational studies include use of
      inappropriate controls and failure to adequately adjust for prognostic imbalance.
      Risk of bias may vary across outcomes (e.g., loss to follow-up may be far less
      for all-cause mortality than for quality of life), a consideration that many
      systematic reviews ignore. In deciding whether to rate down for risk of bias -
      whether for randomised trials or observational studies-authors should not take an
      approach that averages across studies. Rather, for any individual outcome, when
      there are some studies with a high risk, and some with a low risk of bias, they
      should consider including only the studies with a lower risk of bias.

PMID- 22857735
TI  - Synthesis of frame-shifted farnesyl diphosphate analogs.
AB  - A set of synthetic approaches were developed and applied to the synthesis of
      eight frame-shifted farnesyl diphosphate (FPP) analogs. These analogs bear
      increased or decreased methylene units between the double bonds and/or
      diphosphate moieties of the isoprenoid structure. Evaluation versus mammalian
      FTase revealed that small structural changes can lead to dramatic changes in
      substrate ability.

PMID- 22857736
TI  - Physiological function of microglia.
AB  - Broad interest in the rapidly advancing field of microglial involvement in
      forming neural circuits is evident from the fresh findings published in leading
      journals. This special issue of Neuron Glia Biology contains a special collection
      of research articles and reviews concerning the new appreciation of microglial
      function in the normal physiology of the brain that extends beyond their
      traditionally understood role in pathology.

PMID- 22857738
TI  - Microglia in development: linking brain wiring to brain environment.
AB  - Microglia are enigmatic non-neuronal cells that infiltrate and take up residence
      in the brain during development and are thought to perform a surveillance
      function. An established literature has documented how microglia are activated by
      pathogenic stimuli and how they contribute to and resolve injuries to the brain.
      However, much less work has been aimed at understanding their function in the
      uninjured brain. A series of recent in vivo imaging studies shows that microglia
      in their resting state are highly motile and actively survey their neuronal
      surroundings. Furthermore, new data suggest that microglia in their resting state
      are able to phagocytose unwanted synapses and in this way contribute to synaptic
      pruning and maturation during development. Coupled with their exquisite
      sensitivity to pathogenic stimuli, these data suggest that microglia form a link
      that couples changes in brain environment to changes in brain wiring. Here we
      discuss this hypothesis and propose a model for the role of microglia during
      development in sculpting brain connectivity.

PMID- 22857737
TI  - Neonatal rat microglia derived from different brain regions have distinct
      activation responses.
AB  - The regional heterogeneity of neuronal phenotypes is a well-known phenomenon.
      Whether or not glia derived from different brain regions are phenotypically and
      functionally distinct is less clear. Here, we show that microglia, the resident
      immune cells of the brain, display region-specific responses for activating
      agents including glutamate (GLU), lipopolysaccharide (LPS) and adenosine 5'
      triphosphate (ATP). Primary microglial cultures were prepared from brainstem
      (Brs), cortex (Ctx), hippocampus (Hip), striatum (Str) and thalamus (Thl) of 1
      day-old rats and were shown to upregulate the release of nitric oxide (NO) and
      brain-derived neurotrophic factor (BDNF) in a region- and activator-specific
      manner. With respect to ATP specifically, ATP-induced changes in microglial tumor
      necrosis factor-alpha (TNF-alpha) release, GLU uptake and purinergic receptor
      expression were also regionally different. When co-cultured with hypoxia (Hyp)
      injured neurons, ATP-stimulated microglia from different regions induced
      different levels of neurotoxicity. These region-specific responses could be
      altered by pre-conditioning the microglia in a different neurochemical milieu,
      with taurine (TAU) being one of the key molecules involved. Together, our results
      demonstrate that microglia display a regional heterogeneity when activated, and
      this heterogeneity likely arises from differences in the environment surrounding
      the microglia. These findings present an additional mechanism that may help to
      explain the regional selectiveness of various brain pathologies.

PMID- 22857739
TI  - Obtaining enhanced circular dichroism in [4]heterohelicenium analogues.
AB  - Electronic circular dichroism in the three helicenium analogues
      dimethoxyquinacridinium (DMQA(+)), dimethoxychromenoacridinium (DMCA(+)), and
      dimethoxychromenoxanthenium (DMCX(+)) were investigated in vacuum with time
      dependent density functional theory methods using the CAM-B3LYP functional with
      the basis set 6-311++G**. The systems were thoroughly studied by designing
      derivatives with several different electron-donating and -withdrawing
      substituents while at the same time keeping the net charge of the molecule either
      positive, neutral, or negative. Fifty-six derivatives were examined, and we
      identify a superior substitution pattern that is found to be independent of the
      bridging atoms and gives a rotational strength close to 90 * 10(-40) esu(2) cm(2)
      for DMQA, DMCA, and DMCX. The optimal system shows promising applications as a
      chromophore because it has a highly allowed primary electronic transition with an
      angle between the electronic and magnetic transition dipole moments close to 50
      degrees  and its chiroptical response is thereby limited only by the magnetic
      transition.

PMID- 22857740
TI  - C-reactive protein in patients with advanced metastatic renal cell carcinoma:
      usefulness in identifying patients most likely to benefit from initial
      nephrectomy.
AB  - OBJECTIVE: C-reactive protein (CRP) is considered a useful serum marker for
      patients with RCC. However, its clinical utility in advanced metastatic renal
      cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy
      at the onset, is not well studied. PATIENTS AND METHODS: We retrospectively
      evaluated 181 patients with AM-RCC, including 18 patients underwent potentially
      curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received
      medical treatment only. CRP cutoff points were determined by receiver operating
      characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses
      were used for survival tests. RESULTS: ROC analysis suggested that grouping
      patients according to 3 CRP ranges was a rational model. Patients with highly
      elevated CRP (>=67.0 mg/L) presented remarkably poor prognosis despite treatment
      (nephrectomy or medical treatment only). Cox regression models demonstrated that
      risk factors of overall survival for patients who underwent nephrectomy were the
      CRP ranges defined in this study (<=18.0 mg/L, >18.0 and <67.0 mg/L, and >=67.0
      mg/L), ECOG PS (0, 1, and >=2), and number of metastatic organ sites (0-1 and
      >=2). The retrospective design is a limitation of this study. CONCLUSION: Our
      study demonstrated that the serum CRP level is a statistically significant
      prognostic parameter for patients with AM-RCC. The data also indicated that
      pretreatment serum CRP level provides useful prognostic information that helps in
      deciding whether to perform initial nephrectomy for patients with AM-RCC.

PMID- 22857741
TI  - e-MIR2: a public online inventory of medical informatics resources.
AB  - BACKGROUND: Over the past years, the number of available informatics resources in
      medicine has grown exponentially. While specific inventories of such resources
      have already begun to be developed for Bioinformatics (BI), comparable
      inventories are as yet not available for the Medical Informatics (MI) field, so
      that locating and accessing them currently remains a difficult and time-consuming
      task. DESCRIPTION: We have created a repository of MI resources from the
      scientific literature, providing free access to its contents through a web-based
      service. We define informatics resources as all those elements that constitute,
      serve to define or are used by informatics systems, ranging from architectures or
      development methodologies to terminologies, vocabularies, databases or tools.
      Relevant information describing the resources is automatically extracted from
      manuscripts published in top-ranked MI journals. We used a pattern matching
      approach to detect the resources' names and their main features. Detected
      resources are classified according to three different criteria: functionality,
      resource type and domain. To facilitate these tasks, we have built three
      different classification schemas by following a novel approach based on
      folksonomies and social tagging. We adopted the terminology most frequently used
      by MI researchers in their publications to create the concepts and hierarchical
      relationships belonging to the classification schemas. The classification
      algorithm identifies the categories associated with resources and annotates them
      accordingly. The database is then populated with this data after manual curation
      and validation. CONCLUSIONS: We have created an online repository of MI resources
      to assist researchers in locating and accessing the most suitable resources to
      perform specific tasks. The database contains 609 resources at the time of
      writing and is available at http://www.gib.fi.upm.es/eMIR2. We are continuing to
      expand the number of available resources by taking into account further
      publications as well as suggestions from users and resource developers.

PMID- 22857742
TI  - Urothelial carcinoma with orbital metastasis.
AB  - A case of urothelial carcinoma of the bladder with orbital metastasis in a 53
      year-old woman is presented. This case is unique in that the orbit was the sole
      site of metastasis and extensive lymph node dissection was negative just weeks
      before the diagnosis of orbital disease. Although rare, patients with urothelial
      carcinoma and ophthalmic signs or symptoms warrant specialist consultation and
      appropriate imaging.

PMID- 22857744
TI  - Jean B. DeKernion--a gentleman chairman. Interview by Arnold I. Chin.

PMID- 22857743
TI  - Nature of bacterial colonization influences transcription of mucin genes in mice
      during the first week of life.
AB  - BACKGROUND: Postnatal regulation of the small intestinal mucus layer is
      potentially important in the development of adult gut functionality. We
      hypothesized that the nature of bacterial colonization affects mucus gene
      regulation in early life.We thus analyzed the influence of the presence of a
      conventional microbiota as well as two selected monocolonizing bacterial strains
      on the transcription of murine genes involved in mucus layer development during
      the first week of life.Mouse pups (N = 8/group) from differently colonized dams:
      Germ-free (GF), conventional specific pathogen free (SPF), monocolonized with
      either Lactobacillus acidophilus NCFM (Lb) or Escherichia coli Nissle (Ec) were
      analyzed by qPCR on isolated ileal tissue sections from postnatal days 1 and 6
      (PND1, PND6) after birth with respect to: (i) transcription of specific genes
      involved in mucus production (Muc1-4, Tff3) and (ii) amounts of 16S rRNA of
      Lactobacillus and E. coli. Quantification of 16S rRNA genes was performed to
      obtain a measure for amounts of colonized bacteria. RESULTS: We found a
      microbiota-independent transcriptional increase of all five mucus genes from PND1
      to PND6. Furthermore, the relative level of transcription of certain mucus genes
      on PND1 was increased by the presence of bacteria. This was observed for Tff3 in
      the SPF, Ec, and Lb groups; for Muc2 in SPF; and for Muc3 and Muc4 in Ec and Lb,
      respectively.Detection of bacterial 16S rRNA genes levels above the qPCR
      detection level occurred only on PND6 and only for some of the colonized animals.
      On PND6, we found significantly lower levels of Muc1, Muc2 and Muc4 gene
      transcription for Lb animals with detectable Lactobacillus levels as compared to
      animals with Lactobacillus levels below the detection limit. CONCLUSIONS: In
      summary, our data show that development of the expression of genes encoding
      secreted (Muc2/Tff3) and membrane-bound (Muc1/Muc3/Muc4) mucus regulatory
      proteins, respectively, is distinct and that the onset of this development may be
      accelerated by specific groups of bacteria present or absent at the mucosal site.

PMID- 22857745
TI  - Minimum 1.5-year results of "surgeon-tailored" transvaginal mesh repair for
      female stress urinary incontinence and pelvic organ prolapse.
AB  - OBJECTIVE: To evaluate our minimum 1.5-year results with "surgeon-tailored"
      polypropylene mesh (STPM) in stress urinary incontinence treatment and the impact
      of concomitant pelvic organ prolapse repair on functional outcomes. METHODS: All
      patients who were treated for stress urinary incontinence and pelvic organ
      prolapse using STPM between 2006 and 2010 were reviewed. Fifty-two patients
      received transobturator midurethral sling alone. Concomitant pelvic organ
      prolapse repair was performed in 74 (67 cystocele, 14 rectocele). Pre- and
      postoperative evaluation included subjective assessment of the impact of voiding
      and prolapse symptoms with International Consultation on Incontinence-Short Form
      and Prolapse Quality of Life (P-QOL) questionnaires, uroflowmetry, and urodynamic
      studies when necessary. Surgical outcomes at the last follow-up and complications
      were compared between the transobturator midurethral sling and transobturator
      midurethral sling + pelvic organ prolapse repair groups. RESULTS: One-hundred
      eighteen women were available for analysis. With a mean follow-up of 33.4 and
      41.2 months for transobturator midurethral sling and transobturator midurethral
      sling + pelvic organ prolapse repair groups, stress urinary incontinence was
      cured in 86.4% and 81.1% of the patients, respectively. Preoperative urge
      symptoms resolved in 53.8% and 62.5%, and de novo urge symptoms developed in 22%
      and 15% of patients with respect to study groups. Pelvic organ prolapse was cured
      in 98.6% patients, with a significant improvement in all domains of the P-QOL
      questionnaire at the last follow-up. Vaginal mesh erosions were detected in 11
      (14.8%) patients with concomitant pelvic organ prolapse repair. CONCLUSION: STPM
      may represent a cost-effective option for stress urinary incontinence treatment.
      Concomitant pelvic organ prolapse repair with STPM does not affect incontinence
      outcomes and provides high anatomic success and patient satisfaction in the long
      term. However, mesh-related complications with this approach is a major concern
      that deserves further investigation of risk factors and better definition of
      patient selection criteria.

PMID- 22857746
TI  - Editorial comment.

PMID- 22857748
TI  - Laparoscopic cryoablation of renal masses: single-center long-term experience.
AB  - OBJECTIVE: To evaluate perioperative and long-term functional and oncological
      outcomes of laparoscopic cryoablation (LCA) performed at Washington University.
      METHODS: A retrospective chart review was performed evaluating 62 consecutive
      patients who underwent LCA at our institution between 2000 and 2005. RESULTS:
      Mean age-adjusted Charlson Comorbidity Index (CCI) was 6.1 (SD, 2.1; 95%
      confidence interval [CI], 5.6-6.6). Mean tumor size was 2.52 cm (SD, 0.99; CI,
      2.3-2.8). Mean operative time was 162.0 minutes (SD, 66.6; CI, 142.0-182.1). Mean
      estimated blood loss was 84.9 mL (SD, 102; CI, 58.6-111.2). Mean hospital stay
      was 2.6 days (SD, 1.90; CI, 2.1-3.1). The perioperative complication rate was
      9.7% (Clavien 1-2). Among patients with biopsy proven, localized renal cell
      carcinoma, the 6-year Kaplan-Meier estimated disease-free survival (DFS) was 80%;
      cancer-specific survival (CSS) was 100%; and overall survival (OS) was 76.2%.
      Mean follow-up in this subset was 76.0 months (SD, 39.3; CI, 62.7-89.4; n = 35),
      whereas mean time to cancer recurrence was 27.6 months (SD, 11.2; CI, 15.9-39.3;
      n = 6). Tumor size >=2.6 cm was the only predictor of cancer recurrence in a
      multivariate Cox proportional hazards model (hazard ratio [HR] = 28.9; P = .046;
      n = 35). Mean preoperative estimated glomerular filtration rate (eGFR) was 68.3
      (SD, 22.3; CI, 62.1-74.5), compared to 64.5 mL/min/1.73 m(2) (SD, 28.9; CI, 56.5
      72.6) at last follow-up (P = .12; n = 52). Excluding patients requiring secondary
      ablative or extirpative treatments for recurrent renal cell carcinoma,
      preoperative eGFR <60 mL/min/1.73 m(2) (odds ratio [OR] = 88.3; P = .036) and age
      adjusted CCI >=6 (OR = 32.4; P = .046) were the only factors predicting renal
      disease progression on multiple logistic regression (n = 47). CONCLUSION: We
      report what is by far the longest follow-up to date of postlaparoscopic
      cryoablation changes in eGFR and note excellent long-term renal functional
      outcomes. For those willing to accept the potential need for retreatment for
      recurrent disease, LCA offers excellent long-term CSS.

PMID- 22857749
TI  - Editorial comment.

PMID- 22857751
TI  - Assessing renal function after partial nephrectomy using renal nuclear
      scintigraphy and estimated glomerular filtration rate.
AB  - OBJECTIVE: To create a model intended to more accurately characterize renal
      function alteration after partial nephrectomy using a combination of renal
      scintigraphy and estimated glomerular filtration rate (eGFR). METHODS: Thirty-two
      partial nephrectomy patients from a single center with preoperative and
      postoperative renal scans were reviewed. Renal scan data were used to calculate
      proportional eGFR in the involved kidney as a product of the percentage function
      of the operated kidney and total eGFR. Linear regression models were created to
      describe endpoints (postoperative eGFR, involved kidney percent function,
      proportional eGFR) as functions of clinical variables associated with kidney
      damage. RESULTS: For the ipsilateral kidney, mean preoperative percent function
      and eGFR were 50% (SD, 4.8) and 31 mL/min/m(2) (SD, 3.4), respectively;
      postoperative percent function and involved kidney eGFR were 44% (SD, 9.0) and 27
      mL/min/m(2) (SD, 9.0), respectively. Decreased postoperative proportional eGFR
      was significantly associated with increased clamp time and tumor size in
      univariate linear regression models. Clamp time was associated with total eGFR,
      where tumor size was not. Additionally, clamp time and tumor size explain more of
      the variation in proportional eGFR (R(2) = 0.39 and R(2) = 0.17, respectively),
      compared to percent effort and total eGFR. CONCLUSION: Proportional eGFR has a
      stronger association with putative factors of renal dysfunction after partial
      nephrectomy, including clamp time and tumor size, compared to total eGFR,
      indicating it may be a more sensitive marker of renal function after partial
      nephrectomy.

PMID- 22857752
TI  - Hexaminolevulinate-induced fluorescence versus white light during transurethral
      resection of noninvasive bladder tumor: does it reduce recurrences?
AB  - OBJECTIVE: To evaluate the effect of hexaminolevulinate (HAL)-induced
      fluorescence during resection of noninvasive bladder cancer on tumor recurrence
      compared with resection under white light. METHODS: Between 2008 and 2010, 102
      consecutive patients with suspected bladder cancer were randomized to undergo
      transurethral resection with either conventional white light or combination of
      white light and HAL-induced fluorescence. Difference in tumor recurrence rate and
      recurrence-free survival between the 2 groups was evaluated. Subgroup analysis on
      recurrence-free survival was performed for different tumor parameters. RESULTS:
      Cystoscopy at 3 months revealed tumor recurrence in 6 of 45 (13.3%) patients of
      the white light group compared with only 1 of 41 patients of the HAL group (2.4%)
      (P < .001). The recurrence-free rates in white light patients at 12 and 18 months
      were 56.3% and 50.6%, respectively, compared with 91% and 82.5% in HAL patients
      (P = .0006). In subgroup analyses, recurrence-free survival was similar between
      the 2 groups when solitary tumors were treated (P = .3525). However, the HAL
      group had a favorable recurrence-free survival compared with the white light
      group when multifocal tumors (P < .001), primary tumors (P = .0237), recurrent
      tumors (P = .0189), nonaggressive (papillary urothelial neoplasm of low malignant
      potential and low grade) tumors (P = .0204), or aggressive (high grade and
      carcinoma in situ) tumors (P = .0134) were treated. CONCLUSION: HAL significantly
      aids resection of non-muscle-invasive bladder cancer with the result of reduction
      in tumor recurrence rates.

PMID- 22857753
TI  - Editorial comment.

PMID- 22857755
TI  - Clinicopathologic characteristics of 23 cases of invasive low-grade papillary
      urothelial carcinoma.
AB  - OBJECTIVE: To investigate the clinicopathologic and immunohistochemical features
      associated with invasive low-grade papillary urothelial carcinoma (LGPUC), an
      uncommon entity not previously described in published studies. METHODS: A
      multicenter effort originally identified 36 cases diagnosed as invasive LGPUC by
      urologic pathology subspecialists; after re-review, 23 cases were included.
      RESULTS: The average patient age was 69 years (range 46-82); 20 patients were men
      and 3 were women. Stage pT1 disease was present in 19 (83%) of 23 and pT2 disease
      in 4 patients. Of the 23 cases, 13 (57%) showed a single focus of invasion and 10
      multiple foci. The invasive front showed rounded, variably sized nests in 17
      cases (74%) and irregular nests with retraction artifact in 6. Additional
      findings in the noninvasive component included inverted growth in 23, apoptotic
      debris in 5, focal brisk mitotic activity in 4, dispersed chromatin in individual
      cells in 4, and a single atypical cell in 2. Immunohistochemical stains showed
      focal p53 nuclear stain in 23, patchy full-thickness cytokeratin 20 stain in 20,
      full-thickness CD44 expression in 17, and retention of E-cadherin in 23 cases.
      Clinical follow-up was available for all patients. The subsequent diagnosis
      included papilloma in 1 patient (4%), LGPUC in 5 (22%), and high-grade papillary
      urothelial carcinoma in 8 (35%) of the 23 patients, with 5 demonstrating
      invasion. Of the latter patients, 2 developed metastatic disease. CONCLUSION:
      Given the risk of progressive disease in these patients, especially the limited
      stage pT1 disease in most patients, additional studies investigating the
      molecular properties and outcomes associated with this uncommon lesion are
      warranted.

PMID- 22857756
TI  - Effect of prostate-specific antigen screening on metastatic disease burden 10
      years after diagnosis.
AB  - OBJECTIVE: To examine the effect of prostate-specific antigen screening on the
      development of metastatic disease after treatment relative to 1992, the year that
      prostate-specific antigen screening was recommended by the American Urological
      Association. Screening for cancer of the prostate (CaP) with prostate-specific
      antigen has been questioned because of its modest impact on survival in two
      randomized trials. Its impact on the metastatic disease burden in a population
      was not assessed. To account for lead-time bias, we compared the 10-year
      metastasis-free survival rate for the prescreening era group (PRE) to the 15-year
      metastases-free survival rate of the postscreening era group (POST). METHODS:
      From 1986 to 1996, a total of 1721 CaP patients were definitively treated at our
      institution. The cohort was divided into PRE (1986-1992; n = 575) and POST (1993
      1996; n = 1146). PRE patients were censored at 10 years, and POST patients were
      censored at 15 years. The 10- and 15-year metastasis-free survival rate and the
      characteristics associated with the risk of developing metastatic disease were
      assessed. RESULTS: Median follow up for all patients was 10 years (range 0.1-15
      years), 9.6 years (range 0.1-10 years) for PRE, and 10.25 years (range 0.1-15
      years) for POST. The 10-year PRE versus 15-year POST metastasis-free survival
      rate was 58% versus 65% for high-risk (P < .0001), 79% versus 86% for
      intermediate-risk (P < .0001), and 90% versus 96% (P = .0001) for low-risk
      patients. On multivariable analysis, screening era (P < .0001, hazard ratio =
      4.2, 95% confidence interval = 3.1-5.7), T-stage, biopsy Gleason score, and post
      treatment prostate-specific antigen testing frequency were significant for the
      development of metastatic disease. CONCLUSION: The implementation of prostate
      specific antigen screening in this population is associated with a decrease in
      metastatic disease.

PMID- 22857757
TI  - Editorial comment.

PMID- 22857759
TI  - Prognostic factors and outcomes after definitive treatment of female urethral
      cancer: a population-based analysis.
AB  - OBJECTIVE: To evaluate the prognostic factors and outcomes for a large
      observational cohort of female patients with urethral cancer in the Surveillance,
      Epidemiology, and End Results database. METHODS: We identified 722 women
      diagnosed with urethral cancer from 1983 to 2008 in the Surveillance,
      Epidemiology, and End Results database. Descriptive statistics were used to
      explore the epidemiology, standard treatment practices, and tumor
      characteristics. A total of 359 women with nonmetastatic primary urethral cancer
      were identified for cancer-specific and survival analysis. Kaplan-Meier plots and
      log-rank tests were performed for each potential covariate. A multivariate Cox
      proportional hazards model was performed to evaluate age, demographic factors, T
      stage, nodal status, histologic findings, surgery, and radiotherapy. RESULTS: The
      median overall survival time was 42 months (95% confidence interval 35-57), and
      the 5- and 10-year overall survival rate was 43% and 32%, respectively. The
      median cancer-specific survival (CSS) time was 78 months, and the 5- and 10-year
      CSS rate was 53% and 46%, respectively. On multivariate analysis, black race,
      Stage T3-T4 tumors compared with T1, node-positive disease, nonsquamous
      histologic features, and advanced age were associated with shortened CSS. Surgery
      was associated with longer CSS. Black patients presented with a statistically
      significant greater T stage. CONCLUSION: Advanced age, T stage, node-positive
      disease, nonsquamous histologic features, and black race were associated with
      reduced CSS, and surgical resection was associated with longer CSS. We found that
      black patients present with more advanced tumors and have shorter CSS than white
      women with urethral cancer.

PMID- 22857761
TI  - Editorial comment.

PMID- 22857762
TI  - 120W GreenLight High Performance System laser for benign prostate hyperplasia: 68
      patients with 3-year follow-up and analysis of predictors of response.
AB  - OBJECTIVE: To investigate 3-year postoperative results of photoselective
      vaporization of the prostate using the 120W GreenLight High Performance System
      photoselective vaporization of the prostate (HPS-PVP) for treating benign
      prostate hyperplasia (BPH) >30 mL. METHODS: Records of 68 of 85 men who underwent
      HPS-PVP and were followed up for 3 years were analyzed retrospectively. Patients
      were older than 50 years with prostate volume >30 mL, International Prostate
      Symptom Score (IPSS) >=8, maximum flow rate (Q(max.)) <15 mL/s, and bladder
      outlet obstruction (BOO) index >=20. Parameters, including IPSS and Q(max.), were
      measured at baseline and 6, 12, 24, and 36 months postoperatively. Patients who
      improved by at least 30% from baseline IPSS scores were considered responders,
      and logistic regression analysis was done to determine predictors of response.
      RESULTS: Mean age, prostate volume, IPSS, Q(max.), and operative time were 71.6
      +/- 7.3 years, 50.0 +/- 17.0 mL, 21.7 +/- 7.9, 8.7 +/- 3.1 mL/s, and 60.6 +/-
      31.9 minutes, respectively. Six months postoperatively, 50 (73.5%) patients
      responded with respect to IPSS score, and 40 (58.8%) maintained improvements at 3
      years postoperatively. Analysis at 3-year follow-up showed that for IPSS >=19,
      the higher the IPSS the greater the functional bladder capacity (FBC) and the
      lower the frequency of nocturia; and for BOO index >=40, the higher the BOO index
      the better the response. CONCLUSION: HPS-PVP is a safe and effective procedure
      for treating BPH, having demonstrated that 60% of patients maintained efficacy at
      3 years postoperatively. Baseline IPSS, FBC, nocturia, BOO index, and bladder
      contractility index were valuable for predicting response to surgery.

PMID- 22857763
TI  - Sigmoidocolocystoplasty with ureteral reimplantation for treatment of neurogenic
      bladder.
AB  - OBJECTIVE: To assess the clinical and urodynamic results of
      sigmoidocolocystoplasty in patients with neurogenic bladder dysfunction. METHODS:
      We retrospectively reviewed 78 augmentation enterocystoplasty cases in our
      database from 2005 to 2011 to identify 47 patients who had undergone
      sigmoidocolocystoplasty alone or combined with ureter reimplantation. The
      indications for surgery and postoperative complications were evaluated. Renal
      function preservation, increased postoperative bladder capacity, decreased
      maximal detrusor pressure, and overall patient satisfaction were deemed
      successful outcomes. RESULTS: The mean follow-up period was 24 months. The mean
      bladder capacity increased from 160.6 +/- 128.3 to 468.5 +/- 60.6 mL (P < .001)
      and the maximal detrusor pressure decreased from 31.1 +/- 26.4 to 10.9 +/- 4.5 cm
      H(2)O (P = .002). The serum creatinine level decreased from 270.3 +/- 113.6 to
      174.4 +/- 81.3 MUmol/L (P = .001). Most patients resolved the urinary
      incontinence using clean self-intermittent catheterization. The decrease in the
      mean number of incontinence episodes and pads used daily indicated a marked
      improvement in patients' quality of life. Postoperative complications included
      bowel dysfunction in 5 patients (10.6%), adhesive intestinal obstruction in 4
      (8.5%), deteriorating renal function in 3 (6.4%), and vesicoureteral reflux
      recurrence in 2 patients (4.3%). Nearly all patients expressed satisfaction with
      the urologic management. CONCLUSION: Our results suggest that
      sigmoidocolocystoplasty is safe and effective in treating patients with
      neurogenic bladder dysfunction. Concomitant ureter reimplantation will be
      beneficial for patients with a long history of illness.

PMID- 22857764
TI  - Novel technique for fragment removal after percutaneous management of large
      volume neobladder calculi.
AB  - OBJECTIVE: To describe a novel method for fragment evacuation after percutaneous
      lithotripsy of neobladder calculi. METHODS: The technique was developed using a
      Urovac bladder evacuator, which was attached to a standard 30F Amplatz working
      sheath. RESULTS: The attachment of the Urovac evacuator to the Amplatz sheath
      rapidly evacuated large quantities of stone material. Careful attention should be
      paid to maintaining low-pressure irrigation by ensuring the bladder is not overly
      full and the Urovac device is not vigorously manipulated, to minimize the
      likelihood of bladder injury. CONCLUSION: Percutaneous ultrasonic/hydraulic
      lithotripsy for large-volume neobladder calculi often results in a substantial
      burden of stone fragments that can be difficult to clear using standard
      techniques. Attaching a Urovac bladder evacuator to the 30F Amplatz sheath can
      simplify the management of this task.

PMID- 22857765
TI  - Re: Mirzazadeh M, Nouran MG, Richards KA, et al: Effects of drinking water
      quality on urinary parameters in men with and without urinary tract stones
      (Urology 2012;79:501-507).

PMID- 22857767
TI  - Re: Barbosa et al.: Shock wave lithotripsy associated with greater prevalence of
      hypertension (Urology 2011;78:22-25).

PMID- 22857769
TI  - Re: Patel SR, Nakada SY: Quantification of preoperative stone burden for
      ureteroscopy and shock wave lithotripsy: current state and future recommendations
      (Urology 2011;78:282-285).

PMID- 22857772
TI  - Re: Nelius T, Armstrong ML, Rinard K, et al: Genital piercings: diagnostic and
      therapeutic implications for urologists (Urology 2011;78(5):998-1007).

PMID- 22857774
TI  - Re: Elkoushy MA: Impact of radiological technologists on the outcome of shock
      wave lithotripsy (Urology 2011 [Epub ahead of print]).

PMID- 22857775
TI  - Pseudoaneurysm after laparoscopic partial nephrectomy for an 11-cm renal tumor.
AB  - A case of renal artery pseudoaneurysm (RAP) after partial nephrectomy for an 11
      cm renal tumor is reviewed. Symptoms, computed tomography (CT) scan images and
      angiography are all displayed. A 57-year-old woman was readmitted 4 months after
      she underwent a retroperitoneal laparoscopic partial nephrectomy for an 11-cm
      right renal tumor. Contrast CT revealed a 10.3-cm mass recurrence in the same
      position as her former tumor. Renal arteriography confirmed active bleeding from
      the anterior upper pole segmental branch into a 3 * 3 * 7-cm pseudoaneurysm.
      Percutaneous selective coil angioembolization was successfully performed. The
      remaining kidney parenchyma was fully preserved.

PMID- 22857776
TI  - Biogenic amines in low- and reduced-fat dry fermented sausages formulated with
      konjac gel.
AB  - Biogenic amines in low- and reduced-fat dry fermented sausages made with konjac
      gel (KG) as pork backfat replacer were studied. An increase (P < 0.05) was
      observed in the microbial count during the fermentation process, reaching levels
      of over 8 Log cfu/g of total viable microorganisms and lactic acid bacteria.
      However, no significant differences were observed in the microbiota evolution as
      a function of the reformulation process (fat and konjac gel content). High levels
      of physiological amines (spermidine, spermine, and agmatine) were observed in the
      raw material. From day 2 of the fermentation process an increase (P < 0.05) was
      observed in tyramine and putrescine, which were the predominant amines at the end
      of the storage period. The increase in these amines was proportional to the
      presence of KG and fat reduction. This can also be seen for spermine, with
      agmatine showing the inverse. The biogenic amine levels in these products
      reformulated with KG are not considered to pose a health risk to consumers.

PMID- 22857777
TI  - Medical interpreters as tools: dangers and challenges in the utilitarian approach
      to interpreters' roles and functions.
AB  - OBJECTIVE: This study explores the tensions, challenges, and dangers when a
      utilitarian view of interpreter is constructed, imposed, and/or reinforced in
      health care settings. METHODS: We conducted in-depth interviews and focus groups
      with 26 medical interpreters from 17 different languages and cultures and 39
      providers of five specialties. Grounded theory was used for data analysis.
      RESULTS: The utilitarian view to interpreters' roles and functions influences
      providers in the following areas: (a) hierarchical structure and unidirectional
      communication, (b) the interpreter seen as information gatekeeper, (c) the
      interpreter seen as provider proxy, and (d) interpreter's emotional support
      perceived as tools. CONCLUSION: When interpreters are viewed as passive
      instruments, a utilitarian approach may compromise the quality of care by
      silencing patients' and interpreters' voice, objectifying interpreters' emotional
      work, and exploiting patients' needs. PRACTICE IMPLICATIONS: Providers need to
      recognize that a utilitarian approach to the interpreter's role and functions may
      create interpersonal and ethical dilemmas that compromise the quality of care. By
      viewing interpreters as smart technology (rather than passive instruments), both
      providers and interpreters can learn from and co-evolve with each other, allowing
      them to maintain control over their expertise and to work as collaborators in
      providing quality care.

PMID- 22857778
TI  - Exploring communication pathways to better health: clinician communication of
      expectations for acupuncture effectiveness.
AB  - OBJECTIVE: This study tested a pathway whereby acupuncturists' communication of
      optimism for treatment effectiveness would enhance patients' satisfaction during
      treatment, which in turn would contribute to better pain and function outcomes
      for patients with osteoarthritis of the knee. METHODS: Secondary analysis from a
      2 arm (real vs. sham acupuncture, high vs. neutral expectations) RCT. 311
      patients with knee osteoarthritis received acupuncture over 10-12 sessions.
      Coders rated the degree to which acupuncturists communicated optimism for the
      treatment's effectiveness. Satisfaction with acupuncture was assessed 4 weeks
      into treatment. Pain and function were assessed 6 weeks following treatment.
      RESULTS: Patients experiencing better outcomes were more satisfied with
      acupuncture during treatment, were younger, and had better baseline pain and
      function scores. Satisfaction during treatment was greater when patients
      interacted with more optimistic clinicians and had higher pretreatment
      expectations for acupuncture efficacy. CONCLUSION: Acupuncturists' communication
      of optimism about treatment effectiveness contributed to pain and function
      outcomes indirectly through its effect on satisfaction during treatment. Future
      research should model pathways through which clinician-patient communication
      affects mediating variables that in turn lead to improved health outcomes.
      PRACTICAL IMPLICATIONS: While clinicians should not mislead patients,
      communicating hope and optimism for treatment effectiveness has therapeutic value
      for patients.

PMID- 22857779
TI  - A new microspore embryogenesis system under low temperature which mimics zygotic
      embryogenesis initials, expresses auxin and efficiently regenerates doubled
      haploid plants in Brassica napus.
AB  - BACKGROUND: Microspore embryogenesis represents a unique system of single cell
      reprogramming in plants wherein a highly specialized cell, the microspore, by
      specific stress treatment, switches its fate towards an embryogenesis pathway. In
      Brassica napus, a model species for this phenomenon, incubation of isolated
      microspores at 32 degrees C is considered to be a pre-requisite for embryogenesis
      induction. RESULTS: We have developed a new in vitro system at lower temperature
      (18 degrees C) to efficiently induce microspore embryogenesis throughout two
      different developmental pathways: one involving the formation of suspensor-like
      structures (52.4%) and another producing multicellular embryos without suspensor
      (13.1%); additionally, a small proportion of non-responsive microspores followed
      a gametophytic-like development (34.4%) leading to mature pollen. The suspensor
      like pathway followed at 18 degrees C involved the establishment of asymmetric
      identities from the first microspore division and an early polarity leading to
      different cell fates, suspensor and embryo development, which were formed by
      cells with different organizations and endogenous auxin distribution, similar to
      zygotic embryogenesis. In addition, a new strategy for germination of microspore
      derived embryos was developed for achieving more than 90% conversion of embryos
      to plantlets, with a predominance of spontaneous doubled haploids plants.
      CONCLUSION: The present work reveals a novel mechanism for efficient microspore
      embryogenesis induction in B. napus using continuous low temperature treatment.
      Results indicated that low temperature applied for longer periods favours an
      embryogenesis pathway whose first division originates asymmetric cell identities,
      early polarity establishment and the formation of suspensor-like structures,
      mimicking zygotic embryogenesis. This new in vitro system provides a convenient
      tool to analyze in situ the mechanisms underlying different developmental
      pathways during the microspore reprogramming, breaking or not the cellular
      symmetry, the establishment of polarity and the developmental embryo patterning,
      which further produce mature embryos and plants.

PMID- 22857780
TI  - Avanafil for the treatment of erectile dysfunction: a multicenter, randomized,
      double-blind study in men with diabetes mellitus.
AB  - OBJECTIVE: To prospectively assess the safety and effectiveness of the
      investigational phosphodiesterase 5 inhibitor avanafil to treat erectile
      dysfunction in men with diabetes mellitus. PATIENTS AND METHODS: This 12-week,
      multicenter, double-blind, placebo-controlled study conducted between December
      15, 2008, and February 11, 2010, randomized 390 men with diabetes and erectile
      dysfunction 1:1:1 to receive avanafil, 100 mg (n=129), avanafil, 200 mg (n=131),
      or placebo (n=130). Coprimary end points assessed changes in the percentage of
      sexual attempts in which men were able to maintain an erection of sufficient
      duration to have successful intercourse (Sexual Encounter Profile [SEP] 3),
      percentage of sexual attempts in which men were able to insert the penis into the
      partner's vagina (SEP 2), and International Index of Erectile Function erectile
      function domain score. RESULTS: Compared with placebo, least-squares mean change
      from baseline to study end in SEP 3, SEP 2, and International Index of Erectile
      Function erectile function domain score were significantly improved with both
      avanafil, 100 mg (P<=.002), and avanafil, 200 mg (P<.001). Additional analyses
      indicated that successful intercourse could be initiated in 15 minutes or less
      through more than 6 hours after avanafil dosing. Adverse events most commonly
      reported with avanafil treatment were headache, nasopharyngitis, flushing, and
      sinus congestion. CONCLUSION: Avanafil was safe and effective for treating
      erectile dysfunction in men with diabetes and was effective as early as 15
      minutes and more than 6 hours after dosing. The adverse events seen with avanafil
      were similar to those seen with other phosphodiesterase 5 inhibitors. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier NCT00809471.

PMID- 22857781
TI  - Caging peroxide: anion-templated synthesis and characterization of a rare-earth
      cluster.
AB  - Sequestration of peroxide derived from molecular oxygen has resulted in the
      templated synthesis of a terbium picolinate cluster, isolated as a 2D sodiated
      network in the solid state. This first example of an air-stable rare-earth
      peroxide cluster represents key evidence for a peroxide-containing intermediate
      in rare-earth-cluster-catalyzed oxidation reactions. Luminescent and magnetic
      properties have also been investigated.

PMID- 22857782
TI  - Antihypertensive profile of 2-thienyl-3,4-methylenedioxybenzoylhydrazone is
      mediated by activation of the A2A adenosine receptor.
AB  - Several N-acylhydrazone derivatives synthesized from safrole have been found to
      promote intense vasodilation and antihypertensive activity. The present work
      describes the synthesis and antihypertensive profile of 2-thienyl-3,4
      methylenedioxybenzoylhydrazone (LASSBio-1027), a new analogue of the lead
      compound 3,4-methylenedioxybenzoyl-2-thienylhydrazone. Thoracic aortas from
      Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were prepared
      for isometric tension recording. Noninvasive blood pressure measurements were
      made during 14 days of intraperitoneal (10 mg/kg) or oral (20 mg/kg)
      administration of LASSBio-1027. LASSBio-1027 exhibited partially endothelium
      dependent vasorelaxant activity, which was attenuated in the presence of l-NAME,
      glibenclamide, or ZM 241385. LASSBio-1027 exhibited an antihypertensive effect in
      SHR during 14 days of intraperitoneal or oral administration, but did not induce
      a hypotensive effect in normotensive WKY rats. LASSBio-1027-induced vascular
      relaxation of aortas from WKY rats was mediated by the activation of A(2A)
      adenosine receptors. Docking studies and binding assays suggested that LASSBio
      1027 has affinity for A(2A) and A(3) adenosine receptors. This new N
      acylhydrazone derivative represents a potential strategy for the treatment of
      arterial hypertension.

PMID- 22857783
TI  - A survey of hospitals to determine the prevalence and characteristics of
      healthcare coalitions for emergency preparedness and response.
AB  - Previous reports have identified the development of healthcare coalitions as the
      foundation for disaster response across the United States. This survey of acute
      care hospitals characterizes the current status of participation by US hospitals
      in healthcare coalitions for emergency preparedness planning and response. The
      survey results show the nearly universal nature of a coalition approach to
      disaster response. The results suggest a need for wide stakeholder involvement
      but also for flexibility in structure and organization. Based on the survey
      results, the authors make recommendations to guide the further development of
      healthcare coalitions and to improve local and national response to disasters.

PMID- 22857784
TI  - Fluorescent magnetic nanoparticles for magnetically enhanced cancer imaging and
      targeting in living subjects.
AB  - Early detection and targeted therapy are two major challenges in the battle
      against cancer. Novel imaging contrast agents and targeting approaches are
      greatly needed to improve the sensitivity and specificity of cancer theranostic
      agents. Here, we implemented a novel approach using a magnetic micromesh and
      biocompatible fluorescent magnetic nanoparticles (FMN) to magnetically enhance
      cancer targeting in living subjects. This approach enables magnetic targeting of
      systemically administered individual FMN, containing a single 8 nm
      superparamagnetic iron oxide core. Using a human glioblastoma mouse model, we
      show that nanoparticles can be magnetically retained in both the tumor
      neovasculature and surrounding tumor tissues. Magnetic accumulation of
      nanoparticles within the neovasculature was observable by fluorescence intravital
      microscopy in real time. Finally, we demonstrate that such magnetically enhanced
      cancer targeting augments the biological functions of molecules linked to the
      nanoparticle surface.

PMID- 22857785
TI  - Increased morning salivary cortisol levels in older adults with nonamnestic and
      multidomain mild cognitive impairment.
AB  - Exposure to elevated glucocorticoid levels has a detrimental impact on cognitive
      function. In the present study, elderly individuals were classified according to
      their cognitive status to (i) cognitively healthy; (ii) amnestic; (iii)
      nonamnestic; or (iv) multidomain, with an extensive cognitive profiling. Salivary
      cortisol samples were taken at awakening, evening and night. We report that,
      compared to cognitively normal control individuals, subjects with nonamnestic or
      multidomain mild cognitive impairment profiles show increased salivary cortisol
      levels, immediately after awakening, but not in the evening or at night.
      Importantly, individuals with amnestic mild cognitive impairment did not show
      this increase in salivary cortisol levels. We also found that higher morning
      cortisol levels were associated with a lower global cognitive state, as well as
      poorer score in executive function and visuoconstructive praxes, verbal fluency,
      and a worse free immediate recall of items from a word list. These findings open
      new avenues to the use of salivary cortisol levels as a possible biomarker for
      nonamnestic and multidomain mild cognitive impairment in elderly subjects.

PMID- 22857786
TI  - Presence of the viral genome in the myocardial tissue of patients without
      clinical suspicion of myocarditis.

PMID- 22857787
TI  - Improved training tolerance by supplementation with alpha-Keto acids in untrained
      young adults: a randomized, double blind, placebo-controlled trial.
AB  - BACKGROUND: Exercise causes a variety of physiological and metabolic changes that
      can in turn reduce exercise tolerance. One of the potential mechanisms
      responsible for fatigue is "exercise-induced hyperammonemia". Previous studies
      have shown that supplementation with amino acids can increase training tolerance.
      The alpha-keto acids are biochemical analogs of amino acids and can be converted
      to amino acids through transamination, thus reducing the cellular ammonia level.
      This double blind, placebo-controlled study was designed to investigate the
      effects of alpha-keto acid supplementation (KAS) on training tolerance, training
      effect, and stress-recovery state. METHODS: Thirty-three untrained young male
      adults underwent four weeks of training (5 sessions/week; 30 minutes running at
      the individual anaerobic threshold followed by 3 x 3 minute sprints/each
      session). Throughout the 4 weeks of training and one week of recovery, subjects
      took alpha-ketoglutarate (AKG group, 0.2 g/kg/d, n = 9), branched-chain keto
      acids (BCKA group, 0.2 g/kg/d, n = 12) or isocaloric placebo (control group, n =
      12) daily. RESULTS: The 4th week training volume, maximum power output and muscle
      torque were higher in the AKG group (175 +/- 42 min, 412 +/- 49 Watts and 293 +/-
      58 Newton meters, respectively, P<0.05) and the BCKA group (158 +/- 35, 390 +/-
      29 and 273 +/- 47, P<0.05) than in the control group (92 +/- 70, 381 +/- 67 and
      233 +/- 43). The general stress and emotional exhaustion as assessed by the rest
      stress-questionnaire-sport after the 3rd week of training increased significantly
      in the control group (P<0.05), but not in the KAS groups. CONCLUSIONS: Under KAS,
      subjects could bear a higher training volume and reach a higher power output and
      peak muscle torque, accompanied by a better stress-recovery-state. Thus, KAS
      improves exercise tolerance and training effects along with a better stress
      recovery state. Whether the improved training tolerance by KAS is associated with
      effects on ammonia homeostasis requires further observation.

PMID- 22857788
TI  - Impact of grade separator on pedestrian risk taking behavior.
AB  - Pedestrians on Delhi roads are often exposed to high risks. This is because the
      basic needs of pedestrians are not recognized as a part of the urban transport
      infrastructure improvement projects in Delhi. Rather, an ever increasing number
      of cars and motorized two-wheelers encourage the construction of large numbers of
      flyovers/grade separators to facilitate signal free movement for motorized
      vehicles, exposing pedestrians to greater risk. This paper describes the
      statistical analysis of pedestrian risk taking behavior while crossing the road,
      before and after the construction of a grade separator at an intersection of
      Delhi. A significant number of pedestrians are willing to take risks in both
      before and after situations. The results indicate that absence of signals make
      pedestrians behave independently, leading to increased variability in their risk
      taking behavior. Variability in the speeds of all categories of vehicles has
      increased after the construction of grade separators. After the construction of
      the grade separator, the waiting time of pedestrians at the starting point of
      crossing has increased and the correlation between waiting times and gaps
      accepted by pedestrians show that after certain time of waiting, pedestrians
      become impatient and accepts smaller gap size to cross the road. A Logistic
      regression model is fitted by assuming that the probability of road crossing by
      pedestrians depends on the gap size (in s) between pedestrian and conflicting
      vehicles, sex, age, type of pedestrians (single or in a group) and type of
      conflicting vehicles. The results of Logistic regression explained that before
      the construction of the grade separator the probability of road crossing by the
      pedestrian depends on only the gap size parameter; however after the construction
      of the grade separator, other parameters become significant in determining
      pedestrian risk taking behavior.

PMID- 22857789
TI  - Novel, panzootic and hybrid genotypes of amphibian chytridiomycosis associated
      with the bullfrog trade.
AB  - Global amphibian declines are linked with the presence of specific, highly
      virulent genotypes of the emerging fungal disease chytridiomycosis caused by
      Batrachochytrium dendrobatidis (Bd) known as the global panzootic lineage (Bd
      GPL). The global trade in amphibians for human consumption is suspected to have
      facilitated emergence of the disease, but evidence to support this is largely
      lacking. Here, we investigated the role the Lithobates catesbeianus (North
      American bullfrog) trade in spreading Bd genotypes by comparing strains
      associated with L. catesbeianus to a global panel using 36 sequenced loci from
      multiple chromosomal regions. Most bullfrogs were infected with Bd-GPL genotypes,
      but we also detected novel, highly divergent Bd genotypes (Bd-Brazil) from a live
      bullfrog in a US market and from native Brazilian anurans in the Atlantic Forest
      where bullfrogs are widely farmed. Sexual reproduction was also detected for the
      first time in Bd in the form of a hybrid genotype between the Bd-GPL and Bd
      Brazil lineages in the Atlantic Forest. Despite the demonstration that ribosomal
      RNA types in Bd fail to undergo concerted evolution (over 20 sequence types may
      be found in a single strain), the Bd-GPL and Bd-Brazil lineages form largely
      separate clusters of related internal transcribed spacer (ITS) RNA sequences.
      Using ITS sequences, we then demonstrate the presence of Bd-Brazil in Japan,
      primarily on invasive L. catesbeianus. The finding that Bd is capable of sexual
      reproduction between panzootic and endemic genotypes emphasizes the risk of
      international wildlife trade as a source of additional Bd epizootics owing to
      hybridization.

PMID- 22857790
TI  - Evaluation of real-time location systems in their hospital contexts.
AB  - OBJECTIVE: The purpose of the research was to assess real-time location systems
      (RTLS) that have been implemented in U.S. hospitals. We examined the type of uses
      to which RTLS have been put, the degree of functionality of the various
      technologies and software, and the organizational effects of implementing RTLS.
      METHODS: The project was a 3-year qualitative study of 23 U.S. hospitals that had
      implemented RTLS for the purpose of tracking assets, personnel, and/or patients.
      We observed the systems in use and conducted 80 semi-structured interviews with
      hospital personnel and vendors. In order to protect the confidentiality of the
      hospitals and vendors in our sample, we conducted an aggregate analysis of our
      findings rather than providing evaluations of specific technologies or hospital
      case studies. RESULTS: The most important findings from our research were (1)
      substandard functionality of most real-time location systems in use and (2)
      serious obstacles to effective deployment of the systems due to the material and
      organizational constraints of the hospitals themselves. We found that the current
      best use of RTLS is for asset tracking, but importantly it requires whole
      hospital deployment as well as centralized control of the system, preferably by
      materials management or biomedical engineering departments. DISCUSSION: There are
      serious technological, material, and organizational barriers to the
      implementation of RTLS, and these barriers need to be overcome if hospitals are
      to maximize the potential benefits of these systems. CONCLUSION: In addition to
      considering the available technological options, hospitals must assess their
      unique environments, including the myriad material and organizational constraints
      that will affect the success of RTLS implementation.

PMID- 22857791
TI  - Household mold as a predictor of asthma risk: recent progress, limitations, and
      future directions.

PMID- 22857792
TI  - Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand
      (FASLG) mutation.
AB  - BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is characterized by
      chronic nonmalignant lymphoproliferation, accumulation of double-negative T
      cells, hypergammaglobulinemia G and A, and autoimmune cytopenia. OBJECTIVES:
      Although mostly associated with FAS mutations, different genetic defects leading
      to impaired apoptosis have been described in patients with ALPS, including the
      FAS ligand gene (FASLG) in rare cases. Here we report on the first case of
      complete FAS ligand deficiency caused by a homozygous null mutant. METHODS:
      Double-negative T-cell counts and plasma IL-10 and FAS ligand concentrations were
      determined as ALPS markers. The FASLG gene was sequenced, and its expression was
      analyzed by means of Western blotting. FAS ligand function was assessed based on
      reactivation-induced cell death. RESULTS: We describe a patient born to
      consanguineous parents who presented with a severe form of ALPS caused by FASLG
      deficiency. Although the clinical presentation was compatible with a homozygous
      FAS mutation, FAS-induced apoptosis was normal, and plasma FAS ligand levels were
      not detectable. This patient carries a homozygous, germline, single-base-pair
      deletion in FASLG exon 1, leading to a premature stop codon (F87fs x95) and a
      complete defect in FASLG expression. The healthy parents were each heterozygous
      for the mutation, confirming its recessive trait. CONCLUSION: FAS ligand
      deficiency should be screened in patients presenting with ALPS features but
      lacking the usual markers, including plasma soluble FAS ligand and an in vitro
      apoptotic defect. An activation-induced cell death test could help in
      discrimination.

PMID- 22857793
TI  - Preventing disease in the 21st century: the importance of maternal and early
      infant diet and nutrition.

PMID- 22857794
TI  - Autoimmunity in primary antibody deficiency is associated with protein tyrosine
      phosphatase nonreceptor type 22 (PTPN22).
AB  - BACKGROUND: The 1858T allele of protein tyrosine phosphatase nonreceptor type 22
      (PTPN22; R620W) exhibits one of the strongest and most consistent associations
      with sporadic autoimmune disease. Although autoimmunity is common in patients
      with primary antibody deficiency (PAD), it remains unknown whether its
      pathogenesis is similar when it arises in this context compared with in
      immunocompetent patients. OBJECTIVE: We set out to determine whether the 1858T
      allele of PTPN22 was associated with PAD or with autoimmunity in the context of
      PAD. METHODS: We genotyped rs2476601 (g.1858C>T), a single nucleotide
      polymorphism encoding substitution of arginine for tryptophan in PTPN22 (R620W),
      in 193 patients with PAD and 148 control subjects from an Australian cohort. We
      also performed a subgroup analysis according to the presence of autoimmunity and
      B-cell phenotypes. RESULTS: C/T and T/T PTPN22 genotypes were more common in
      patients with PAD than in the matched control subjects (C/T, 18.1% vs 9.5%; T/T,
      1.04% vs 0.6%). The T allele was associated with an increased risk of PAD
      relative to control subjects (odds ratio, 2.10; 95% CI, 1.11-4.00). The
      distribution of genotypes in control subjects was similar to those reported
      previously and did not deviate significantly from Hardy-Weinberg equilibrium. We
      found a strong association between the 1858T allele and PAD with coexistent
      autoimmune diseases. In patients with PAD and autoimmunity, 16 (43.2%) of 37 had
      at least one T allele of PTPN22 compared with 27 (17.3%) of 156 with the C/C
      genotype (P=.0014; odds ratio, 3.64; 95% CI, 1.68-7.88). We found no evidence
      that this effect was mediated by enrichment of CD21low B cells. CONCLUSION: The
      1858T PTPN22 allele is strongly associated with autoimmunity in patients with
      PAD.

PMID- 22857795
TI  - Sensitization and allergic histories differ between black and white pregnant
      women.
AB  - BACKGROUND: Racial differences in allergic diseases have been reported, with
      black subjects suffering disproportionately compared with white subjects,
      although such studies have been more commonly done in pediatric populations.
      OBJECTIVE: We sought to determine whether there are differences in rates of
      allergic sensitization or prior diagnoses of asthma, hay fever, or eczema in
      black and white pregnant women. METHODS: Women were recruited during pregnancy
      (regardless of allergic history) as part of a birth cohort study in the Detroit
      metropolitan area and were interviewed about prior doctors' diagnoses of asthma,
      hay fever/nasal allergies/allergic rhinitis, and eczema. Blood samples were
      collected, total IgE levels were determined, and specific IgE levels were
      measured for Alternaria alternata, cat, cockroach, dog, Dermatophagoides farinae,
      short ragweed, timothy grass, and egg. RESULTS: Black women (n = 563) were more
      likely than white women (n = 219) to have had at least 1 specific IgE level of
      0.35 IU/mL or greater (62.5% vs 40.2%, P < .001). Black women had higher total
      IgE levels (geometric mean, 47.8 IU/mL [95% CI, 42.5-53.8 IU/mL] vs 20.0 IU/mL
      [95% CI, 16.2-24.6 IU/mL]; P < .001, Wilcoxon rank sum test). Black women were
      more likely to have had a prior doctor's diagnosis of asthma (22.7% vs 16.0%, P =
      .04) and eczema (21.9% vs 14.8%) but not hay fever (white women: 17.5% vs black
      women: 15.7%, P = .55). Associations persisted for total IgE levels, having 1 or
      more positive allergen-specific IgE levels, and eczema after adjusting for common
      socioeconomic or environmental variables. CONCLUSIONS: Racial differences in
      allergic sensitization and diagnoses were present, even after controlling for
      various factors. Future research should focus on prevention to ameliorate these
      disparities.

PMID- 22857796
TI  - Cross-sector sponsorship of research in eosinophilic esophagitis: a collaborative
      model for rational drug development in rare diseases.
AB  - Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood
      disorder, and assessment tools to accurately determine disease activity,
      remission, and natural history have long been inadequate. Clinical outcome end
      points able to assess the effectiveness of candidate therapeutic agents in
      clinical trials have been a particular deficiency and are urgently needed. With
      no approved therapy available to patients and with the prevalence of EoE on the
      increase, collaborative approaches to drug development are becoming ever more
      important. We describe a collaborative effort mobilized across institutions,
      including both the public and private sectors, that was initiated within the past
      18 months expressly to address the need for further clinical research into the
      cause and treatment of EoE. Collaborators include the North American Society of
      Pediatric Gastroenterology, Hepatology and Nutrition; the International
      Gastrointestinal Eosinophilic Researchers; and the US Food and Drug
      Administration. This effort has resulted in the elucidation of several parameters
      essential for effective EoE registration trials, including the need for
      clinically meaningful end points that measure changes in clinical symptoms in
      addition to the assessment of intraepithelial mucosal eosinophilia. The
      development and use of biomarkers, particularly in early-phase drug development,
      have become an important focus for investigations that might reduce clinical
      reliance on serial invasive monitoring. The concerted efforts described here to
      develop rational therapeutics and drug development paradigms in EoE also appear
      to provide a model for effective collaboration in the context of drug development
      for rare diseases and perhaps more generally for public health initiatives.

PMID- 22857797
TI  - Sputum cell counts and methacholine hyperresponsiveness as asthma outcomes.

PMID- 22857798
TI  - No own-age bias in 3-year-old children: more evidence for the role of early
      experience in building face-processing biases.
AB  - This study aimed to investigate the presence of an own-age bias in young children
      who accumulated different amounts of early experience with child faces.
      Discrimination abilities for upright and inverted adult and child faces were
      tested using a delayed two-alternative, forced-choice matching-to-sample task in
      two groups of 3-year-old children, one composed of first-born children and the
      other composed of children who, from the time of their birth, had daily exposure
      to a child face through the presence of an older sibling in their home. Children
      without an older sibling were better at differentiating among adult faces than
      among child faces and showed an inversion effect that was selective for adult
      faces. Children with an older sibling were equally skilled at differentiating
      upright adult and child faces and showed inversion effects of comparable
      magnitude for both face types. Results support the notion that face
      representational space of younger children is tuned to adult faces and suggest
      that age biases during early childhood are dependent on the effects of early
      experience.

PMID- 22857799
TI  - Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis:
      evidence from meta-analysis.
AB  - INTRODUCTION: Toll like receptor 4 (TLR4) expression was found to increase
      markedly in human atherosclerotic lesions, notably on macrophages and endothelial
      cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor
      activity and a subsequently diminished inflammatory response, and may
      subsequently reduce atherosclerosis (AS) risk. However, the results of molecular
      epidemiological studies remained inconsistent. MATERIALS AND METHODS: The PubMed,
      CNKI databases were searched for all articles available. The OR corresponding to
      the 95% confidence interval (95% CI) was used to assess the association between
      TLR4 Asp299Gly polymorphism and risk of AS. RESULTS: 15 case-control studies with
      9,989 cases and 6,746 controls were available for this analysis. For control
      subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from
      0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with
      significantly risk of AS (OR=1.02, 95% CI=0.83 - 1.26 for G versus A and OR=0.96,
      95% CI=0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.
      CONCLUSION: These findings indicated that TLR4 Asp299Gly polymorphism may not
      play a role in AS development.

PMID- 22857800
TI  - Initiation of rivaroxaban following low molecular weight heparin for
      thromboprophylaxis after total joint replacement: the Safe, Simple Transitions
      (SST) study.
AB  - INTRODUCTION: No data are available regarding appropriate strategies for the
      transition of patients undergoing total hip or knee replacement (THR/TKR) surgery
      from subcutaneous low molecular weight heparin (LMWH) to rivaroxaban. This study
      determined the pharmacodynamic effects of rivaroxaban on the first day of
      administration compared with serial administration in patients who had
      transitioned to rivaroxaban 22-28 hours after the last once-daily LMWH dose (or
      12-18 hours after the last twice-daily LMWH dose). METHODS: Patients undergoing
      THR or TKR surgery who had received at least one post-operative LMWH dose were
      included in this open-label, single-arm, multicentre study. Measurements of anti
      Factor Xa activity and prothrombin time were made on the first and third days of
      daily rivaroxaban administration. The effects of age and renal function on these
      parameters, and safety and tolerability, were assessed. RESULTS: Fifty-six
      patients were enrolled in the Safe, Simple Transitions (SST) study; 52 patients
      comprised the intention-to-treat population. Mean anti-Factor Xa activity
      increased slightly but significantly from day 1 to day 3, whereas the area under
      the concentration-time curve (AUC) was similar on days 1 and 3. Mean prothrombin
      time was slightly prolonged on day 1 compared with day 3; the AUC was
      significantly increased (p<0.0001). The pharmacodynamic effects of rivaroxaban
      were slightly increased in older patients and those with reduced renal function.
      There were no cases of venous thromboembolism or bleeding and no unexpected
      adverse events. CONCLUSION: Initiating rivaroxaban approximately 12 or 24 hours
      after the last LMWH dose (as appropriate) provides a simple, well-tolerated
      transition strategy for thromboprophylaxis in patients undergoing THR/TKR
      surgery.

PMID- 22857801
TI  - Cerebral infarction in beta-thalassemia intermedia: breaking the silence.
AB  - Despite remarkable advances in understanding cerebrovascular disease attributed
      to sickle cell anemia, data from other hemoglobinopathies have only recently
      started to emerge. Several brain magnetic resonance imaging studies confirm a
      high prevalence of silent ischemic lesions in patients with beta-thalassemia
      intermedia, especially in splenectomized adults who are transfusion-independent
      and those with elevated platelet counts. Large-vessel disease is also common in
      this patient population but without apparent association with silent white matter
      infarcts, leaving smaller arteriolar involvement as a potential explanation. The
      hypothesized pathophysiology is multifactorial with hypercoagulability and
      toxicity from free iron species playing major roles. The long-term sequelae of
      such covert findings is unknown, although experience from patients with sickle
      cell anemia confirms their association with subsequent overt stroke and
      neurocognitive deficits. The roles of transfusion and antiplatelet therapy to
      prevent the occurrence and progression of silent ischemic lesions in patients
      with beta-thalassemia intermedia should be the focus of future trials.

PMID- 22857802
TI  - Comment on Monte Carlo calculation of the dose distributions of two 106Ru eye
      applicators [Radiother Oncol 49 (1998) 191-196].

PMID- 22857803
TI  - Equivalent doses for gynecological patients undergoing IMRT or RapidArc with
      kilovoltage cone beam CT.
AB  - PURPOSE: To investigate in-field and peripheral kilovoltage cone beam CT (CBCT)
      doses in gynecological patients in comparison with IMRT or RapidArc scatter and
      linac leakage doses. MATERIALS AND METHODS: Monte Carlo codes BEAMnrc/DOSXYZnrc
      were used to simulate dose for daily use of kV CBCT in patients undergoing
      adjuvant pelvic radiotherapy for uterine or ovarian malignancies. Biological
      effectiveness was accounted for using a lineal energy based quality factor. Organ
      equivalent doses (OED) within the treatment field were modeled with linear
      exponential, plateau and linear dose response curves. CBCT doses in peripheral
      regions were compared with IMRT and RapidArc scatter doses as well as linac
      leakage doses. RESULTS: CBCT doses in peripheral regions were on the order of
      linac leakage doses and one order of magnitude lower than IMRT or RapidArc
      scatter doses. OEDs increased slightly, leveled off or even decreased within the
      treatment field with the addition of CBCT doses according to different dose
      response models. CONCLUSION: The results of this study indicate that patients
      undergoing IMRT or RapidArc treatments with daily use of kV CBCT imaging are not
      subjected to additional risk due to CBCT imaging doses.

PMID- 22857804
TI  - Has partial breast irradiation by IORT or brachytherapy been prematurely
      introduced into the clinic?
AB  - In contrast to most new oncology treatments, wide clinical introduction of
      partial breast irradiation (PBI) is not based on level A trial evidence. Despite
      promising phase I/II data, new reports based upon large cohorts of patients
      mention more recurrences and/or complications from PBI compared with whole breast
      irradiation (WBI), necessitating more careful selection of patients for PBI while
      awaiting long term results of major clinical trials. In an attempt to improve
      this we give preoperative PBI within a prospective trial.

PMID- 22857805
TI  - [Are intravenous immunoglobulins useful in severe episodes of autoimmune
      hemolytic anemia?: Comparative results in 21 episodes from a single centre].
AB  - BACKGROUND AND OBJECTIVE: To analyze haemolytic episodes in patients with warm
      antibody autoimmune haemolytic anemia (AIHA) and compare corticosteroids
      treatment with intravenous immunoglobulins (IVIG) (group A) or without IVIG
      (group B). PATIENTS AND METHODS: Observational study that includes 21 haemolytic
      episodes occurred in 17 patients (9 males and 12 females), with a median age of
      59 years (26-82). In group A, 8 episodes received IGIV + corticosteroids and in
      group B, 12 episodes received only corticosteroids and one rituximab. RESULTS:
      Hemoglobin (Hb) value at diagnosis was 1.8 g/dl lower (95% confidence interval:
      0.6 to 3.1; P = .007) in group A, with a median Hb of 6.3g/dl in this group vs
      7.9 g/dl in group B. There were non-significant differences in red blood cells
      transfusion (50 vs 23%; P > .20) and global increase of Hb values (7.3 vs 5.6; P
      > .20). Overall hematological responses were similar: 88 vs 92% (P > .20).
      CONCLUSIONS: Hematological response achieved in more severe episodes with the use
      of IVIG was similar to non-severe episodes treated without IVIG.

PMID- 22857806
TI  - Compatible rhizosphere microbes mediated alleviation of biotic stress in chickpea
      through enhanced antioxidant and phenylpropanoid activities.
AB  - The study was conducted to examine efficacy of a rhizospheric microbial
      consortium comprising of a fluorescent Pseudomonas (PHU094), Trichoderma
      (THU0816) and Rhizobium (RL091) strain on activation of physiological defense
      responses in chickpea against biotic stress caused by the collar rot pathogen
      Sclerotium rolfsii. Results of individual microbes were compared with dual and
      triple strain mixture treatments with reduced microbial load (1/2 and 1/3rd,
      respectively, of individual microbial load compared to single microbe
      application) in the mixtures. Periodical studies revealed maximum activities of
      phenylalanine ammonia lyase [E.C. 4.1.3.5] and polyphenol oxidase [E.C.
      1.14.18.1] and accumulation of total phenol content in chickpea in the triple
      microbe consortium treated plants challenged with the pathogen compared to the
      single microbe and dual microbial consortia. Similarly, the expression of the
      antioxidant enzymes superoxide dismutase [E.C.1.15.1.1] and peroxidase
      [E.C.1.11.1.7] was also highest in the triple microbial consortium which was
      correlated with lesser lipid peroxidation in chickpea under the biotic stress.
      Histochemical staining clearly showed maximum and uniform lignification in
      vascular bundles of chickpea stem sections treated with the triple microbes. The
      physiological responses were directly correlated with the mortality rate as least
      plant mortality was recorded in the triple microbe consortium treated plants. The
      results thus suggest an augmented elicitation of stress response in chickpea
      under S. rolfsii stress by the triple microbial consortium in a synergistic
      manner under reduced microbial load.

PMID- 22857807
TI  - Prevalence of frailty and factors associated with frailty in the elderly
      population of Lleida, Spain: the FRALLE survey.
AB  - The aim of this study was to assess the prevalence of frailty and to identify
      factors associated with frailty in older people living in the community through a
      cross-sectional study of community-dwelling persons age 75 and older. A total of
      640 individuals were interviewed using the FRALLE survey between 2009 and 2010.
      This survey measures frailty through the five Fried criteria, and through
      questions on sociodemographics, health habits, health status, social relations
      and data on health-related quality of life. The mean age of the participants was
      81.3 +/- 5.0; 39.7% were men. The prevalence of frailty was 9.6% (95% confidence
      interval (CI): 7.6-11.5) and that of pre-frailty was 47% (95% CI: 42.7-51.2).
      After the logistic regression, age (over 85 years) (odds ratio (OR): 3.61; 95%
      CI: 1.65-7.91; p<0.001), depressive symptoms (OR: 3.13; 95% CI: 1.37-7.13;
      p=0.0006), comorbidity (OR: 5.20; 95% CI: 1.78-15.16; p=0.0002), cognitive
      impairment (OR: 3.22; 95% CI: 1.48-7.02; p=0.0003), poor social ties (OR: 0.57;
      95% CI: 0.43-0.77; p<0.001) and poor physical health (OR: 0.98; 95% CI: 0.97
      0.98; p<0.001) were significantly associated with frailty. There is great
      variability in the prevalence of frailty depending on the study considered. The
      lack of homogeneity in the measurement of the five criteria, the age of
      participants and the degree of dependence could explain the differences observed.
      Here, the factors associated with frailty were age, comorbidity, cognitive
      impairment and depressive symptoms, while the diversity of social interaction and
      health-related physical function were protective factors.

PMID- 22857808
TI  - Impact of chronic kidney disease on outcomes after abdominal aortic aneurysm
      repair.
AB  - OBJECTIVE: Chronic kidney disease (CKD) is associated with increased morbidity
      and death after open abdominal aortic aneurysm (AAA) repair (OAR). This study
      highlights the effect of CKD on outcomes after endovascular AAA (EVAR) and OAR in
      contemporary practice. METHODS: The National Surgical Quality Improvement Program
      (NSQIP) Participant Use File (2005-2008) was queried by Current Procedural
      Terminology (American Medical Association, Chicago, Ill) code to identify EVAR or
      OAR patients, who were grouped by CKD class as having mild (CKD class 1 or 2),
      moderate (CKD class 3), or severe (CKD class 4 or 5) renal disease. Propensity
      score analysis was performed to match OAR and EVAR patients with mild CKD with
      those with moderate or severe CKD. Comparative analysis of mortality and clinical
      outcomes was performed based on CKD strata. RESULTS: We identified 8701 patients
      who were treated with EVAR (n = 5811) or OAR (n = 2890) of intact AAAs. Mild,
      moderate, and severe CKD was present in 63%, 30%, and 7%, respectively. CKD
      increased (P < .01) overall mortality, with rates of 1.7% (mild), 5.3%
      (moderate), and 7.7% (severe) in unmatched patients undergoing EVAR or OAR.
      Operative mortality rates in patients with severe CKD were as high as 6.2% for
      EVAR and 10.3% for OAR. Severity of CKD was associated with increasing frequency
      of risk factors; therefore, propensity matching to control for comorbidities was
      performed, resulting in similar baseline clinical and demographic features of
      patients with mild compared with those with moderate or severe disease. In
      propensity-matched cohorts, moderate CKD increased the risk of 30-day mortality
      for EVAR (1.9% mild vs 3.2% moderate; P = .013) and OAR (3.1% mild vs 8.4%
      moderate; P < .0001). Moderate CKD was also associated with increased morbidity
      in patients treated with EVAR (8.3% mild vs 12.8% moderate; P < .0001) or OAR
      (25.2% mild vs 32.4% moderate; P = .001). Similarly, severe CKD increased the
      risk of 30-day mortality for EVAR (2.6% mild vs 5.7% severe; P = .0081) and OAR
      (4.1% mild vs 9.9% severe; P = .0057). Severe CKD was also associated with
      increased morbidity in patients treated with EVAR (10.6% mild vs 19.2% severe; P
      < .0001) or OAR (31.1% mild vs 39.6% severe; P = .04). CONCLUSIONS: The presence
      of moderate or severe CKD in patients considered for AAA repair is associated
      with significantly increased mortality and therefore should figure prominently in
      clinical decision making. The high mortality of AAA repair in patients with
      severe CKD is such that elective repair in such patients is not advised, except
      in extenuating clinical circumstances.

PMID- 22857809
TI  - Ezetimibe reduces intimal hyperplasia in rabbit jugular vein graft.
AB  - BACKGROUND: The selective cholesterol transport inhibitor ezetimibe is widely
      used to prevent development of atherosclerosis in patients with
      hypercholesterolemia. However, whether this agent inhibits intimal hyperplasia in
      autologous vein grafts is unknown. The present study was undertaken to clarify if
      ezetimibe reduces cell proliferation and intimal hyperplasia in vein grafts.
      METHODS: Forty-four rabbits were randomly divided into two groups: one group
      received ezetimibe (0.6 mg/kg/d), and the control group did not. Ezetimibe
      administration was started 1 week before rabbits underwent interposition reversed
      autologous jugular vein grafts. The proliferative cells and apoptotic cells were
      counted in the vein grafts 14 days after implantation, and changes in
      acetylcholine-induced relaxation and endothelial intracellular concentration of
      Ca2+ ([Ca2+]i) were examined at 28 days. RESULTS: Ezetimibe reduced serum
      cholesterol and triglyceride. There were fewer proliferating cells in the
      ezetimibe group (5.7%+/-0.2%, n=7) than in the control group (12.8%+/-0.5%, n=7;
      P<.0001) and more apoptotic cells in the ezetimibe group (5.3%+/-0.2%, n=7) than
      in the control group (2.3%+/-0.2%, n=7; P<.0001). Intimal hyperplasia was less in
      the ezetimibe group (46.1+/-6.0 MUm, n=7) than in the control group (76.0+/-2.5
      MUm, n=7; P<.01). Acetylcholine-produced endothelium-dependent relaxation was
      observed only in the ezetimibe group, which was blocked by the nitric oxide (NO)
      synthase inhibitor Nomega-nitro-l-arginine. Acetylcholine increased [Ca2+]i only
      in the ezetimibe group. CONCLUSIONS: Ezetimibe reduced cell proliferation and
      enhanced cell apoptosis, thus inhibiting intimal hyperplasia in rabbit autologous
      vein grafts. Ezetimibe restored the acetylcholine-induced increase in [Ca2+]i in
      endothelial cells and improved endothelium-dependent NO-mediated relaxation in
      the vein graft. Our results suggest that ezetimibe enhances the function of
      endothelial NO through an increase in endothelial [Ca2+]i, thus reducing vein
      graft intimal hyperplasia.

PMID- 22857810
TI  - New temporary internal introducer shunt for brain perfusion during total
      endovascular arch replacement with in situ fenestration technique.
AB  - Complete endovascular arch replacement by in situ fenestration technique requires
      maintenance of cerebral perfusion during the fenestration procedure by an
      extracorporeal femoral-carotid bypass. The bypass has the disadvantages of being
      invasive, requiring a pump, and shunting blood extracorporeally. This report
      describes bench testing and an in vivo experimental animal setup with an
      endovascular, temporary introducer shunt. This technique represents an adjunctive
      step toward a complete endovascular repair for the aortic arch.

PMID- 22857811
TI  - Two cases of misaligned deployment of Valiant Captivia thoracic stent graft.
AB  - Thoracic aortic stent grafts have been widely used. We report two cases of
      proximal misaligned deployment of the Valiant Captivia stent graft after hybrid
      treatment of thoracic aneurysms. This complication has, to our knowledge, never
      been previously reported in the literature with this stent graft. We discuss the
      various factors that may explain this complication. We also describe the bailout
      technique that was carried out.

PMID- 22857814
TI  - A comparison of 0 + 5 versus 5 + 2 applicants to vascular surgery training
      programs.
AB  - OBJECTIVE: The new integrated 0 + 5 vascular surgery (VS) training paradigm
      introduced in 2007 required program directors and faculty to reconsider
      recruiting methods and exposure of medical students to VS. As a means to identify
      variables important for recruitment of 0 + 5 VS applicants, we sought to analyze
      national 0 + 5 VS residency application trends and to compare medical school
      demographics of applicants to both our 0 + 5 residency and 5 + 2 fellowship
      programs. METHODS: Electronic Residency Application Service and National Resident
      Matching Program online public databases were queried to evaluate nationwide
      trends in the number of applicants to integrated VS residency programs between
      2007 and 2010. Demographic data from Electronic Residency Application Service
      applications submitted to our institution's 0 + 5 and 5 + 2 VS training programs
      during the same time period were reviewed. RESULTS: From 2008 to 2011, there were
      190 applicants to our 0 + 5 VS residency program and 161 applicants to our 5 + 2
      fellowship program, with 127 (66.8%) and 122 (75.8%) being United States medical
      graduates, respectively. Annual application volume to our programs over these
      years remained stable for both training pathways (range, 39-49 for 0 + 5
      integrated; range, 39-43 for 5 + 2 traditional). Nationally, applications to 0 +
      5 programs increased sixfold over the same time period (52 in 2007 to 340
      applicants in 2010; P < .001), far exceeding the available training positions.
      Compared with applicants to the 5 + 2 VS fellowships, medical students applying
      to the 0 + 5 programs are more likely to be female, be slightly older, have
      additional postgraduate degrees and publications, have higher United States
      Medical Licensure Examination test scores, and are more likely to be in the top
      quartile of their medical school class. CONCLUSIONS: Nationwide interest in the 0
      + 5 vascular surgery residency training paradigm continues to significantly
      increase. Significant differences exist between the cohorts of 0 + 5 residency
      and 5 + 2 fellowship program applicants at the completion of medical school,
      suggesting that 0 + 5 VS residency programs are attracting a different medical
      student population to the VS specialty. VS program directors should continue to
      foster interest in this new applicant pool through early exposure, mentorship,
      and extracurricular research activities.

PMID- 22857812
TI  - Early versus delayed carotid endarterectomy in symptomatic patients.
AB  - BACKGROUND: Delayed carotid endarterectomy (CEA) after a stroke or transient
      ischemic attack (TIA) is associated with risks of recurrent neurologic symptoms.
      In an effort to preserve cerebral function, urgent early CEA has been recommended
      in many circumstances. We analyzed outcomes of different time intervals in early
      CEA in comparison with delayed treatment. STUDY DESIGN: Retrospective chart
      review from a single university hospital tertiary care center between April 1999
      and November 2010 revealed 312 patients who underwent CEA following stroke or
      TIA. Of these 312 patients, 69 received their CEA within 30 days of symptom onset
      and 243 received their CEA after 30 days from symptom onset. The early CEA cohort
      was further stratified according to the timing of surgery: group A (27 patients),
      within 7 days; group B (17), between 8 and 14 days; group C (12), between 15 and
      21 days; and group D (12), between 22 and 30 days. Demographic data as well as 30
      day (mortality, stroke, TIA, and myocardial infarction) and long-term (all-cause
      mortality and stroke) adverse outcome rates were analyzed for each group. These
      were also analyzed for the entire early CEA cohort and compared against the
      delayed CEA group. RESULTS: Demographics and comorbid conditions were similar
      between groups. For 30-day outcomes, there were no deaths, 1 stroke (1.4%), 0
      TIAs, and 0 myocardial infarctions in the early CEA cohort; in the delayed CEA
      cohort, there were 4 (1.6%), 4 (1.6%), 2 (0.8%), and 2 (0.8%) patients with these
      outcomes, respectively (P > .05 for all comparisons). Over the long term, the
      early group had one ipsilateral stroke at 17 months and the delayed group had two
      ipsilateral strokes at 3 and 12 months. For long-term outcomes, there were 16
      deaths in the early CEA cohort (21%) and 74 deaths in the delayed CEA cohort
      (30%, P > .05). Mean follow-up times were 4.5 years in the early CEA cohort and
      5.8 years in the delayed CEA cohort. CONCLUSIONS: There were no differences in 30
      day and long-term adverse outcome rates between the early and delayed CEA
      cohorts. In symptomatic carotid stenosis patients without evidence of
      intracerebral hemorrhage, carotid occlusion, or permanent neurologic deficits
      early carotid endarterectomy can be safely performed and is preferred over
      delaying operative treatment.

PMID- 22857815
TI  - Distribution, elimination, and toxicity of silver nanoparticles and silver ions
      in rats after 28-day oral exposure.
AB  - We report the results of a 28-day oral exposure study in rats, exposed to <20 nm
      noncoated, or <15 nm PVP-coated silver nanoparticles ([Ag] = 90 mg/kg body weight
      (bw)), or AgNO(3) ([Ag] = 9 mg/kg bw), or carrier solution only. Dissection was
      performed at day 29, and after a wash-out period of 1 or 8 weeks. Silver was
      present in all examined organs with the highest levels in the liver and spleen
      for all silver treatments. Silver concentrations in the organs were highly
      correlated to the amount of Ag(+) in the silver nanoparticle suspension,
      indicating that mainly Ag(+), and to a much lesser extent silver nanoparticles,
      passed the intestines in the silver nanoparticle exposed rats. In all groups
      silver was cleared from most organs after 8 weeks postdosing, but remarkably not
      from the brain and testis. Using single particle inductively coupled plasma mass
      spectrometry, silver nanoparticles were detected in silver nanoparticle exposed
      rats, but, remarkably also in AgNO(3) exposed rats, hereby demonstrating the
      formation of nanoparticles from Ag(+)in vivo that are probably composed of silver
      salts. Biochemical markers and antibody levels in blood, lymphocyte proliferation
      and cytokine release, and NK-cell activity did not reveal hepatotoxicity or
      immunotoxicity of the silver exposure. In conclusion, oral exposure to silver
      nanoparticles appears to be very similar to exposure to silver salts. However,
      the consequences of in vivo formation of silver nanoparticles, and of the long
      retention of silver in brain and testis should be considered in a risk assessment
      of silver nanoparticles.

PMID- 22857817
TI  - Lentigo maligna.
AB  - Lentigo maligna is a type of in situ melanoma. It develops mainly in middle-aged
      and elderly individuals on areas of the skin chronically exposed to sunlight. It
      progresses to its invasive form, lentigo maligna melanoma, in 5% to 50% of cases.
      Management of lentigo maligna is open to debate, with a notable lack of
      randomized trials and specific guidelines and protocols. Early diagnosis and
      treatment is necessary to achieve cure if possible and prevent progression to
      invasive melanoma with the corresponding risk of metastasis. The treatment of
      choice for lentigo maligna is surgery. When surgery is not possible, other
      alternatives are available although outcomes and rates of recurrence are
      variable. The objective of this study was to review the diagnostic methods and
      criteria for lentigo maligna, as well as the different surgical options and
      alternatives to surgery, in order to provide information on the best approach in
      each case. 

PMID- 22857818
TI  - Your mind wanders weakly, your mind wanders deeply: objective measures reveal
      mindless reading at different levels.
AB  - When the mind wanders, attention turns away from the external environment and
      cognitive processing is decoupled from perceptual information. Mind wandering is
      usually treated as a dichotomy (dichotomy-hypothesis), and is often measured
      using self-reports. Here, we propose the levels of inattention hypothesis, which
      postulates attentional decoupling to graded degrees at different hierarchical
      levels of cognitive processing. To measure graded levels of attentional
      decoupling during reading we introduce the sustained attention to stimulus task
      (SAST), which is based on psychophysics of error detection. Under experimental
      conditions likely to induce mind wandering, we found that subjects were less
      likely to notice errors that required high-level processing for their detection
      as opposed to errors that only required low-level processing. Eye tracking
      revealed that before errors were overlooked influences of high- and low-level
      linguistic variables on eye fixations were reduced in a graded fashion,
      indicating episodes of mindless reading at weak and deep levels. Individual
      fixation durations predicted overlooking of lexical errors 5s before they
      occurred. Our findings support the levels of inattention hypothesis and suggest
      that different levels of mindless reading can be measured behaviorally in the
      SAST. Using eye tracking to detect mind wandering online represents a promising
      approach for the development of new techniques to study mind wandering and to
      ameliorate its negative consequences.

PMID- 22857819
TI  - New graduate nurses' experiences in their first year of practice.
AB  - AIMS: This study aimed to explore new graduates' experiences of entering the
      nursing workforce in NSW, Australia, and to identify factors that impact on their
      transition to the workforce, satisfaction and likelihood of retention.
      BACKGROUND: The nature of new graduates' experiences in their first year of
      employment has been shown to have a significant impact on their future career
      directions. It is well reported that often these experiences are stressful and
      unsatisfying. METHODS: A mixed method cross sectional design was used combining
      quantitative and qualitative approaches. Data was gathered by online survey and
      focus groups. RESULTS: A total of 282 new graduates, aged 21 to 54, responded to
      the online survey (response rate 24%). Overall, respondents were satisfied with
      their recruitment process (mean 3.54) and support for professional development
      (mean 3.37) but job satisfaction was rated lower (mean 2.91). Qualitative
      findings from focus groups and survey comments revealed a number of key factors
      impacting on the experience of transition for new graduates. These are; the
      nature of the workplace environment, the level and nature of support available to
      new graduates, together with their propensity to learn and adapt to workplace
      cultures and to accommodate their own expectations and the expectations of
      others, and to a lesser degree, the amount of prior experience. CONCLUSION: There
      is an urgent need to develop and test a range of evidence based approaches that
      will both empower nurses and embed systematic approaches that enable equitable
      and contextually relevant stewardship of new graduate nurses into the future.

PMID- 22857821
TI  - [Do differences exist in the neurosurgical handling of intracranial lesions of
      pregnant patient? Outcomes of our experience and literature review].
AB  - OBJECTIVE: The main objective of our work is to revise our neurosurgical
      experience in pregnant patient and to carry out a revision of the related
      literature in order to optimize the neurosurgical handling of these kind of
      patients. METHOD: Retrospective study between august 1993 and June 2010. We
      included patients who were pregnant at the time and who presented any trace of
      cranial neurosurgical or spinal disease. RESULTS: The research includes the cases
      of 12 patients aged between 17 and 37 years old with an average age of 28.8 years
      old. The average gestation period was of 24.17 weeks, finding 50% of the patients
      within their third three-month period of pregnancy at the moment of diagnosis,
      25% in their second three-month period and the remaining 25% in their first three
      month period. The mean follow-up duration for this series was 84 months. 4 of
      them presented brain vascular lesions, 5 presented brain tumor lesions, 1 of them
      presented Chiari malformation, one lumbar disc herniation and 1 patient suffered
      from traumatic intracraneal hemorrhage. 8 of the 12 patients were subjected to
      neurosurgical procedures under general anesthetic, 2 for aneurysm embolizations
      and 2 for conservative treatments. Between the neurosurgical procedures 6
      craniotomies were done, of wich 4 were to resection of the tumor and 2 for
      aneurysm clippings. There were done a transesfenoidal approach and a lumbar
      microdiscectomy. 2 of the 6 patients given craniotomies required external
      ventricular drainage before the operation. 5 elective cesareans were done in the
      group of patients given the craniotomies whilst of the rest the pregnancy was
      allowed to bring to term for reasons of pulmonary maturity. In our patients there
      were no cases of therapeutic abortion. There was found no morbidity no mortality
      neither in the mother nor in the fetus related to surgery. CONCLUSIONS: In our
      experience with pregnant patients who suffered from neurosurgical lesion and in
      the experience we got from the revision of the related literature, the surgery of
      intracranial lesions is well tolerated by the mothers and the fetus. It must
      though be considered, the possibility of labor through cesarean depending on the
      fetus' lung maturity.

PMID- 22857820
TI  - Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic
      fibrosis patient subpopulations.
AB  - BACKGROUND: Clinical observations suggest that Mycobacterium avium complex (MAC)
      and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis (CF)
      patients with different characteristics and risk factors, but this has never been
      demonstrated within a single prospective cohort. METHODS: We studied 50 MABSC
      positive and 23 MAC-positive patients from a French prevalence study of non
      tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with
      MABSC and MAC were analyzed by nested case-control studies, with two NTM-negative
      controls matched by age, sex and center for each case. RESULTS: MAC-positive
      patients were significantly older than MABSC-positive patients (mean [SD] age,
      23.1 [10.2] vs 17.4 [8.3] years, p=0.013), and were also older at CF diagnosis
      (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p=0.015); they tended to be less
      frequent of the DeltaF508/DeltaF508 genotype (33.3 vs 61.1%, p=0.17) and to use
      pancreatic extracts less frequently (82.4 vs 97.6%, p=0.07). Risk factors
      identified by multivariate analysis were: i) in the MAC case-control study, an
      older age at CF diagnosis (p=0.004); ii) in the MABSC case-control study, at
      least one course of intravenous antibiotics (p=0.01) and more frequent isolation
      of Aspergillus (p=0.03). CONCLUSIONS: MAC affects adult patients with a mild form
      of CF, whereas MABSC affects younger patients with more severe CF and more
      frequent intravenous antimicrobial treatment.

PMID- 22857823
TI  - Immune senescence and vaccines to prevent herpes zoster in older persons.
AB  - Varicella-zoster virus (VZV) T-cell-mediated immunity (VZV-CMI) in older persons
      prevents latent VZV in sensory neurons from reactivating to cause herpes zoster.
      VZV-CMI declines greatly with aging, but can be restored by the licensed zoster
      vaccine. However, the vaccine-induced boost in VZV-CMI (which determines the
      efficacy of the vaccine) is a function of the age of the vaccinee, and the
      duration of this boost wanes with time. Both factors influence the value of this
      vaccine. To understand these aging effects, limited information about the
      phenotypic and functional differences in VZV-CMI in old and young persons are
      reviewed, as well as the reversal of these differences by vaccination. Based on
      information from these studies some potential approaches to improving prevention
      of herpes zoster are discussed.

PMID- 22857822
TI  - Using epigenetic mechanisms to understand the impact of common disease causing
      alleles.
AB  - Many common genetic variants have been identified to be associated with
      autoimmune diseases such as Type I diabetes. Methods to identify these genetic
      loci have become powerful, but deciphering the functional effects of these
      variants in disease progression remains a major challenge. Recent studies have
      shown that single nucleotide polymorphisms are associated with altered DNA
      methylation and chromatin accessibility, suggesting that genetic variants can
      alter epigenetic features and epigenetic variations can mediate genetic
      variability. In this review, we highlight recent studies that have examined the
      relationship between genetics and epigenetics, and how epigenetic studies may
      complement genetic studies in understanding the impact of common disease causing
      alleles.

PMID- 22857824
TI  - Chemistry of DNA minor groove binding agents.
AB  - Most of the clinically used anticancer drugs exert their antitumor effect by
      damaging the replication machinery of DNA either by covalent or non-covalent
      binding. Intercalation and groove fitting are the major modes of non-covalent
      interaction. Small crescent shaped molecules have been claimed to bind with DNA
      via minor grooves. A plethora of hybrid molecules based on distamycin or
      netropsin have been synthesised with the objectives of improved selectivity and
      specificity with no/reduced unwanted side effects. This review critically and
      objectively describes the previously known hybrid DNA minor groove binding agents
      based on five membered, distamycin or netropsin. Moreover, the future use of six
      membered benzamides has also been highlighted. Special emphasis has been put on
      developing structure-activity relationships of DNA minor groove binding agents.

PMID- 22857825
TI  - Exclusive elemental diet impacts on the gastrointestinal microbiota and improves
      symptoms in patients with chronic pouchitis.
AB  - BACKGROUND: Treatment resistant chronic pouchitis causes significant morbidity.
      Elemental diet is effective treatment for Crohn's disease. Since pouchitis shares
      some similarities to Crohn's disease we hypothesised that elemental diet may be
      an effective treatment. METHOD: Seven pouchitis patients (with ulcerative
      colitis) were studied. All had active pouchitis with a pouch disease activity
      index (PDAI) >=7. Exclusion criteria were recent NSAIDs, antibiotics or
      probiotics. Sufficient elemental diet to achieve energy requirements was
      provided. Flexible-pouchoscopy was performed, and the Cleveland Global Quality of
      Life score (CGQoL), Pouch Disease Activity Index (PDAI) and BMI were recorded at
      baseline and following 28 days of elemental diet. Faecal samples were also
      collected at these time points and analysed for major bacterial groups using
      culture independent fluorescence in situ hybridisation. Data were analysed using
      Wilcoxon's signed-rank test. RESULTS: Following 28 days of exclusive elemental
      diet, median stool frequency decreased from 12 to 6 per day (p=0.028), median
      clinical PDAI decreased from 4 to 1 (p=0.039). There was no significant
      difference in quality of life scores or PDAI before and following treatment.
      There was a trend towards an increase in the concentration of Clostridium
      coccoides-Eubacterium rectale (median 7.9 to 8.5 log10/g, p=0.08) following
      exclusive elemental diet. CONCLUSION: Treatment with four weeks elemental diet
      appeared to improve the symptoms of chronic pouchitis in some patients but is not
      an effective strategy for inducing remission. Although a potential symptom
      modifier, elemental diet cannot be recommended for the routine treatment of
      active pouchitis.

PMID- 22857826
TI  - Prenatal ultrasound and urological anomalies.
AB  - Prenatal ultrasound is an integral part of caring for pregnant women in the
      United States. Although surprisingly few data exist to support the clinical
      benefit of screening ultrasound during pregnancy, its use continues to rise.
      Urologic anomalies are among the most commonly identified, with overall detection
      sensitivity approaching 90%. Prenatal hydronephrosis is the most frequently
      identified finding and predicting postnatal pathology based on its presence can
      be difficult. As the degree of fetal hydronephrosis increases so does the risk of
      true urinary tract pathology. Diagnoses that require more urgent care include
      causes of lower urinary tract obstruction and bladder and cloacal exstrophy.

PMID- 22857827
TI  - The current management of the neurogenic bladder in children with spina bifida.
AB  - The urological care of the neurogenic bladder consists of 2 components: medical
      management with preservation of renal function and quality-oflife issues with
      achieving dryness and independence of bladder and bowel management. Both
      components are equally important for patients to live a healthy and fulfilled
      life. This report explores the diagnosis of the neurogenic bladder; quality-of
      life issues that caregivers and patients should expect; the importance of primary
      care knowledge of the neurogenic bladder and treatment; surgical options; the
      transition of pediatric patients to adult care; and the importance of caregiver
      and patient understanding of their disease, treatment options, and
      responsibilities.

PMID- 22857828
TI  - Inguinal and genital anomalies.
AB  - Problems of the groin and genitalia are a common presenting complaint in both
      pediatrician's offices and emergency departments. The authors endeavor to provide
      a comprehensive review of the most common inguinal and genital anomalies
      encountered by the pediatrician, with a special focus on examination and
      management.

PMID- 22857829
TI  - Functional bladder problems in children: pathophysiology, diagnosis, and
      treatment.
AB  - Functional lower urinary tract problems, bladder and bowel problems, or
      dysfunctional elimination syndrome are all terms that describe the common array
      of symptoms that include overactive bladder syndrome, voiding postponement,
      stress incontinence, giggle incontinence, and dysfunctional voiding in children.
      This article discusses the nomenclature and looks at the pathophysiology of
      functional bladder disorders from a different perspective than has been the norm
      in the past. Some standard medical treatments as well as some newer forms of
      treatment are outlined. Treatment algorithms for urinary frequency and urinary
      incontinence have been created to help the practitioner manage the patient.

PMID- 22857830
TI  - Current options in the management of primary vesicoureteral reflux in children.
AB  - The management of vesicoureteral reflux (VUR) is varied and remains
      controversial, which is likely because children with VUR have different risks for
      urinary tract infection or renal injury. Consequently, the treatment of VUR needs
      to be individualized based on the patient's characteristics. In this article, the
      authors review the medical and surgical management options for VUR in the
      pediatric population. The authors hope to provide a systematic approach to
      determine which treatment is optimal for a specific patient.

PMID- 22857831
TI  - Management of primary vesicoureteral reflux in children: editorial commentary.
AB  - Decisions are needed about the clinical management of children with
      vesicoureteral reflux (VUR) and a standardized risk-specific treatment approach
      is needed. Clinicians and researchers must begin to think creatively about VUR.
      Clinicians are beginning to understand that there are a variety of abnormalities
      in specific host defenses that might predispose some children to recurrent
      urinary tract infection, and that knowledge of these deficiencies may lead to
      therapies designed to compensate for them. There is also much to be learned about
      host inflammatory response to kidney infection.

PMID- 22857832
TI  - Hydronephrosis: a view from the inside.
AB  - Unilateral ureteropelvic junction obstruction (UPJO) is the most common
      prenatally detected disease leading to hydronephrosis. The obstructive anatomic
      lesion leads to varying degrees of hydronephrosis, ranging from no apparent
      effect on renal function to atrophy. Furthermore, the natural course of
      hydronephrosis varies from spontaneous resolution to progressive deterioration
      and may take upwards of 3 years for a kidney to declare itself. The objectives of
      this article are to update our knowledge regarding the evaluation and management
      of UPJO in depth and to discuss the emerging value of urinary proteome analysis
      to the clinical arena.

PMID- 22857833
TI  - Update on the management of disorders of sex development.
AB  - A number of factors have contributed to a sharp increase in the number of
      publications related to disorders of sex development (DSD) in the past 5 years,
      namely: the establishment of a consensus in 2006 about nomenclature,
      investigations and the need to treat these patients in a multidisciplinary
      setting; increase of the knowledge base about genetic mechanisms of normal and
      abnormal sex development; critical appraisal about the timing and nature of
      genital surgery in patients with DSD. Herein, the authors present a comprehensive
      review with up-to-date data about the approach to the newborn with ambiguous
      genitalia as well as the diagnosis and management of the most common DSD.

PMID- 22857834
TI  - Management of disorders of sex development: editorial commentary.
AB  - In 2005, the Lawson Wilkins Pediatric Endocrine Society and the European Society
      for Pediatric Endocrinology convened a conference on intersex to review clinical
      management practices and data from long-term health-related and gender-related
      outcomes research and to identify key areas for future research. Romao and
      colleagues provide an overview of the evolving changes after publication of this
      guidance, informed by experiences in their multidisciplinary clinic. This
      commentary highlights and expands on several of the topics explored, with a
      special emphasis on the psychosocial aspects of care for persons affected by
      disorders of sex development and their families.

PMID- 22857836
TI  - Urolithiasis in children: surgical approach.
AB  - Over the past 3 decades, minimally invasive stone surgery has completely
      overtaken open surgical approaches to upper tract pediatric urolithiasis.
      Progressing from least to most minimally invasive, extracorporeal shock wave
      lithotripsy, ureteroscopy, and percutaneous nephrolithotomy are the surgical
      methods of today for kidney and ureteral stones. The choice of treatment modality
      is individualized in children, considering patient age, stone size, number,
      location, and anatomic and clinical contributing factors. The purpose of this
      article is to review these techniques for pediatric upper urinary tract stones
      and summarize outcomes and complications.

PMID- 22857835
TI  - Urolithiasis in children: medical approach.
AB  - Childhood urolithiasis is an evolving condition with an increasing incidence and
      prevalence over the last 2 decades. Over that time the underlying cause has
      shifted from predominantly infectious to metabolic in nature. This review
      describes the pathophysiology, underlying metabolic abnormalities, clinical
      presentation, evaluation, and management of childhood urolithiasis. A
      comprehensive metabolic evaluation is essential for all children with renal
      calculi, given the high rate of recurrence and the importance of excluding
      inherited progressive conditions.

PMID- 22857837
TI  - Issues in febrile urinary tract infection management.
AB  - Urinary tract infections are common occurrences in the pediatric age group and
      are a cause of significant morbidity and expense. The understanding of the
      consequences and sequelae of febrile urinary tract infections led to revision of
      standard protocols initiated by the American Academy of Pediatrics (AAP) in 1999.
      A less invasive protocol of radiologic evaluation has been the major outcome of
      the revised AAP guidelines. Emphasis on prevention of recurrent febrile urinary
      tract infections has also led to therapeutic programs that are centered less
      around the use of prophylactic antibiotics than has previously been the practice.

PMID- 22857838
TI  - Evidence basis for individualized evaluation and less imaging in febrile urinary
      tract infection: an editorial commentary.
AB  - The past decade has seen a remarkable retreat from previous dogma regarding
      urinary tract infections (UTIs). Less aggressive imaging is now recommended
      because although vesicoureteral reflux (VUR) is frequently found in children with
      a history of febrile UTIs, most VUR resolves spontaneously and we do not have
      evidence that treatment of the rest improves outcome. Available evidence suggests
      urine testing for UTI can be less aggressive as well, focusing on those with the
      most risk factors for UTI, those with the most severe illness, and those at
      highest risk of complications.

PMID- 22857839
TI  - Advances in the surgical pediatric urologic armamentarium.
AB  - The surgical armamentarium of the pediatric urologist has changed greatly in the
      past 2 decades on account of new technology and careful adaptation of minimally
      invasive techniques in children. Conventional laparoscopy, robotic-assisted
      laparoscopy, laparoendoscopic single-site surgery, and endourologic surgery have,
      to varying degrees, provided new approaches to urologic surgery in the pediatric
      population. This article reviews the technology and adaptations behind these
      recent advances as well as their current applications in management of urologic
      disease in children.

PMID- 22857840
TI  - Bladder dysfunction in children science fiction or [corrected] science fact:
      editorial comment.
AB  - Functional bladder problems in children are often insidious and are frequently
      ignored by the child, by parents, and by many caregivers. Consideration of both
      the urinary and bowel outlets, and more recently, of the corticospinal tracts and
      brain reveal great complexity in this condition. In this article, the author
      addresses many of these issues in depth with a familiar personal experience
      derived from many years of dedicated consideration of these problems. Bladder
      dysfunction in the child is in many ways the pediatric urologist's hypertension
      diagnosis. Like antihypertensive therapy, bladder retraining strategies must be
      adhered to for life.

PMID- 22857841
TI  - Pediatric urologic oncology.
AB  - This article reviews common pediatric urologic cancers involving the
      genitourinary system. Rhabdomyosarcoma may occur in the bladder, prostate,
      paratesticular regions, vagina, or uterus. Some of these locations, such as the
      paratesticular region, have a more favorable outcome. Benign neoplasms account
      for the majority of pediatric testicular tumors and most are managed with testis
      sparing surgery. Most genitourinary malignancies are expected to have a good
      outcome. One focus of treatment is organ preservation but not at the expense of a
      good oncologic outcome. Late sequelae of anticancer therapy are a concern and
      every attempt is made to decrease the intensity of tumor treatment.

PMID- 22857842
TI  - Geintourinary malignancies in children: editorial comment.
AB  - The modern management of pediatric genitourinary malignancies has resulted in
      survival rates that are dramatically better than figures from just a few decades
      ago. This is largely due to advances in multimodal treatment, collaborative
      efforts, and multidisciplinary management. Nevertheless, issues related to long
      term side effects, treatment-related morbidity, and progression or recurrences
      remain important and pressing in terms of research directions and areas for
      improvement. In this Editorial Comment the author attempts to employ the current
      state of the art, masterfully summarized in the accompanying review by Drs
      Grimsby and Ritchey, to provide a view of trends that are likely to become
      increasingly important in the future, highlighting common patterns in treatment
      philosophy seen in other areas of oncology: more selective or patient-tailored
      treatment strategies, refined protocols and -whenever possible- tissue sparing
      and minimally invasive surgical interventions.

PMID- 22857843
TI  - Pediatric urological emergencies.
AB  - Although few children are severely ill when evaluated in the pediatric office,
      developing the skills to recognize an infant or child who requires
      hospitalization is critical. Some children will require treatment in an emergency
      department or direct admission to an inpatient facility, whereas other children
      can be managed as outpatients. Determining when an infant requires an inpatient
      admission is particularly important because the metabolic reserve is less
      abundant in the newborn. Patients with hemodynamic instability must be emergently
      addressed. This article outlines the most common urgent and emergent pediatric
      urological conditions with the goal to direct initial evaluation and treatment.

PMID- 22857844
TI  - Circumcision controversies.
AB  - Despite its long history and common practice, circumcision remains a
      controversial procedure. This article reviews the history of this operation,
      examines the controversy that surrounds it, and emphasizes the performing
      practitioner's responsibility to the patient and his family in guiding them
      through the complicated decision making surrounding newborn circumcision.

PMID- 22857845
TI  - Preface: What pediatricians need to know about urology.

PMID- 22857846
TI  - A pilot plant scale evaluation of a new process aid for enhancing chlorine
      efficacy against pathogen survival and cross-contamination during produce wash.
AB  - Developing food safety intervention technology that can be readily adopted by the
      industry often requires test conditions that match as closely as possible to
      those of commercial food processing operations; yet biosafety risks inherent in
      pathogen studies constrain most experiments to laboratory settings. In this
      study, we report the first semi-commercial pilot-scale evaluation of a new
      process aid, T128, for its impact on enhancing the antimicrobial efficacy of
      chlorinated wash water against pathogen survival and cross-contamination. A non
      pathogenic, BSL-1, strain of Escherichia coli O157:H7 was inoculated onto freshly
      harvested baby spinach leaves and washed with large amounts of freshly cut un
      inoculated iceberg lettuce shreds in wash water with free chlorine periodically
      replenished, in the presence or absence of T128. Changes in water quality and
      pathogen survival and cross-contamination were monitored at every 2 min intervals
      for up to 36 min for each treatment during the wash operation. Results indicated
      that the use of T128 did not significantly (P>0.05) influence the rate of wash
      water deterioration, nor the pathogen populations remaining on the inoculated
      spinach leaves. However, in the absence of T128 (control), survival of E. coli
      O157:H7 in wash water and cross-contamination of un-inoculated lettuce frequently
      occurred when free chlorine in solution dropped below 1mg/l during the wash
      process. In contrast, the use of T128 significantly reduced the occurrence of E.
      coli O157:H7 surviving in wash water and of cross-contamination to un-inoculated
      shredded iceberg lettuce under the same operational conditions, suggesting that
      the application of T128 in a chlorine-based fresh produce sanitization system
      could increase the safety margin of process control on fresh-cut operations.

PMID- 22857847
TI  - Cuboid-navicular tarsal coalition: report of a small case series with description
      of a surgical approach for resection.
AB  - Tarsal coalitions are an uncommon pathology, representing approximately a 1%
      occurrence in the general population, and most commonly diagnosed in the younger
      population. Coalitions between the cuboid and navicular are especially rare. In
      this case series, all patients were young (15-35 years of age), active patients
      with fibrous coalitions at the cuboid-navicular interface; 3 of the 4 patients
      related a past history of ankle sprains on the affected side. After conservative
      treatment was exhausted and a diagnostic injection was performed that eliminated
      the pain, surgical intervention was used that consisted of coalition resection
      and interposition of an adipose graft harvested from the lower leg. All patients
      were able to return to their previous level of activity and remain pain-free at
      the surgical site. Our series of 4 cases of this coalition suggests that,
      although rare, cuboid-navicular coalition should be included in the differential
      diagnosis when patients present with persistent foot pain and suspicion of tarsal
      coalition is high. We also demonstrate that surgical resection of this coalition
      with an interpositional adipose graft provides excellent results.

PMID- 22857848
TI  - Bilateral cadaveric Achilles tendon graft in reconstruction after Achilles tendon
      tumor resection.
AB  - The standard approach to reconstruction after resection of a diffuse-type
      tenosynovial giant cell tumor is a local patch with free flaps. However, in cases
      in which the Achilles tendon involvement is extensive, and the entire tendon must
      be removed, an autologous flap graft might not be adequate to allow a return to
      function. We report a case of a 52-year-old female patient who developed
      bilateral tumors of the Achilles tendon, with a 10-year duration. By the time,
      she sought medical help, both Achilles tendons required removal. We chose to use
      Achilles tendon allografts to replace the Achilles tendons. Postoperatively, the
      patient did well. The allograft shortened the recovery time, and the patient
      regained full ankle range of motion.

PMID- 22857849
TI  - Restenosis after carotid artery stenting: remaining issues.

PMID- 22857851
TI  - Clinical spectrum of disease associated with ATP1A3 mutations.

PMID- 22857852
TI  - Survey of naturally and conventionally cured commercial frankfurters, ham, and
      bacon for physio-chemical characteristics that affect bacterial growth.
AB  - Natural and organic food regulations preclude the use of sodium nitrite/nitrate
      and other antimicrobials for processed meat products. Consequently, processors
      have begun to use natural nitrate/nitrite sources, such as celery juice/powder,
      sea salt, and turbinado sugar, to manufacture natural and organic products with
      cured meat characteristics but without sodium nitrite. The objective of this
      study was to compare physio-chemical characteristics that affect Clostridium
      perfringens and Listeria monocytogenes growth in naturally cured and
      traditionally cured commercial frankfurters, hams, and bacon. Correlations of
      specific product characteristics to pathogen growth varied between products and
      pathogens, though water activity, salt concentration, and product composition
      (moisture, protein and fat) were common intrinsic factors correlated to pathogen
      growth across products. Other frequently correlated traits were related to curing
      reactions such as % cured pigment. Residual nitrite and nitrate were
      significantly correlated to C. perfringens growth but only for the ham products.

PMID- 22857850
TI  - Restenosis after carotid artery stenting and endarterectomy: a secondary analysis
      of CREST, a randomised controlled trial.
AB  - BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial
      (CREST), the composite primary endpoint of stroke, myocardial infarction, or
      death during the periprocedural period or ipsilateral stroke thereafter did not
      differ between carotid artery stenting and carotid endarterectomy for symptomatic
      or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to
      compare the composite endpoint of restenosis or occlusion. METHODS: Patients with
      stenosis of the carotid artery who were asymptomatic or had had a transient
      ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and
      were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000,
      and July 18, 2008. In this secondary analysis, the main endpoint was a composite
      of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by
      duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a
      reduction in diameter of the target artery of at least 70%, diagnosed by a peak
      systolic velocity of at least 3.0 m/s. Studies were done in CREST-certified
      laboratories and interpreted at the Ultrasound Core Laboratory (University of
      Washington). The frequency of restenosis was calculated by Kaplan-Meier survival
      estimates and was compared during a 2-year follow-up period. We used proportional
      hazards models to assess the association between baseline characteristics and
      risk of restenosis. Analyses were per protocol. CREST is registered with
      ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their
      assigned treatment within 30 days of randomisation and had eligible
      ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid
      endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting
      (Kaplan-Meier rate 6.0%) and 62 who had carotid endarterectomy (6.3%) had
      restenosis or occlusion (hazard ratio [HR] 0.90, 95% CI 0.63-1.29; p=0.58).
      Female sex (1.79, 1.25-2.56), diabetes (2.31, 1.61-3.31), and dyslipidaemia
      (2.07, 1.01-4.26) were independent predictors of restenosis or occlusion after
      the two procedures. Smoking predicted an increased rate of restenosis after
      carotid endarterectomy (2.26, 1.34-3.77) but not after carotid artery stenting
      (0.77, 0.41-1.42). INTERPRETATION: Restenosis and occlusion were infrequent and
      rates were similar up to 2 years after carotid endarterectomy and carotid artery
      stenting. Subsets of patients could benefit from early and frequent monitoring
      after revascularisation. FUNDING: National Institute of Neurological Disorders
      and Stroke and Abbott Vascular Solutions.

PMID- 22857853
TI  - Effect of very fast chilling and aging time on ultra-structure and meat quality
      characteristics of Chinese Yellow cattle M. Longissimus lumborum.
AB  - Objectives of the current study were to evaluate meat ultra-structure and
      tenderness variation at different chilling regimes and aging times. Hot boned
      longissimus lumborum of 18 Chinese crossbred cattle were divided into 4 portions
      per side. One portion underwent very fast chilling (VFC, at -21  degrees C to
      achieve core temperature of 0  degrees C, then transferred to another incubator
      at 2  degrees C), whereas other treatments were held at 14, 7 and 0  degrees C
      for 10 h postmortem, respectively. At 10 h postmortem, all muscles were vacuum
      aged at 2  degrees C for 21 d. Cold shortened muscles had greatest absolute
      amount of tenderization during aging. VFC caused lowest sarcomere length, with
      super-contractions, ruptured Z-lines and myofibril cleavage, but improved
      myofibril fragmentation index (MFI), with no significant negative effect on
      toughness. Overall, aging improved the meat quality of cold shortened beef.
      Moreover, it should be prudent in some applications to apply VFC to excised
      muscles from a food safety perspective, and to improve tenderness compared to
      cold-shortened muscles.

PMID- 22857855
TI  - Heritability variations of body linearity and obesity indicators during growth.
AB  - Longitudinal as well as cross-sectional studies have shown variations with age in
      heritability estimates for body dimensions from infancy to adulthood, even though
      the patterns of variation are not completely clear. Further study on this subject
      is of great interest and may help obesity interventions for preventing or
      treating obesity in children. Therefore, the aim of the present study is to
      analyse the changes in the genetic and environmental architecture of 8 body
      linearity and obesity-related phenotypes during the growth process in a cross
      sectional sample of 1018 nuclear families from the province of Biscay (Basque
      Country, Spain). The contribution of additive genetic effects to the variation of
      the analysed traits was estimated by a variance component analysis using the
      SOLAR program. Moderate to high heritability estimates were obtained for all 8
      anthropometric phenotypes (38.23-65.98%). The heritability values show an
      increasing trend with age and in the course of the entire ontogenetic development
      two age periods were remarkable. At 7(+)-8(+) years of age a strong increase in
      heritability estimates was found for all the anthropometric phenotypes, except
      for the sum of skinfolds (SF6), reflecting the biological significance of genes
      during mid-childhood. During puberty, most of the obesity related phenotypes
      showed their highest heritability values while linear measurements and weight
      presented a decrease in the genetic contributions. In conclusion, this study
      confirms that additive genetic influences have a considerable effect on body
      linearity and obesity-related traits throughout the growth period and that mid
      childhood and puberty are very sensitive periods in human life cycle.

PMID- 22857854
TI  - Dietary and commensal derived nutrients: shaping mucosal and systemic immunity.
AB  - The intestine serves as the primary site of nutrient absorption in the body while
      also harboring the highest burden of commensal microflora and representing a
      major portal of pathogen exposure. As such, the immune network of the intestine
      relies on both dietary and commensal derived signals to guide appropriate
      function. Recent advances highlight the role of dietary derived nutrients and
      commensal derived metabolites in shaping gastrointestinal immunity. In
      particular, vitamin A has been shown to have dominant and pleiotropic effects in
      the intestine. In addition, dietary derived AHR ligands and commensal derived
      metabolites are now emerging as important players in mucosal immunity. Thus
      nutrition, commensal microflora and the mucosal immune system are all intimately
      connected.

PMID- 22857856
TI  - Hypocalcaemia, alcohol drinking and viroimmune responses in ART recipients.
AB  - Metabolic perturbations associated with HIV and antiretroviral therapies are
      widespread. Unfortunately, research has predominantly focused in cardiometabolic
      problems, neglecting other important areas. In fact, the immune-calcium-skeletal
      interface has been understudied despite its potential relevance in people living
      with HIV (PLWH). Using a case-control methodology, 200 PLWH receiving medical
      care were enrolled and stratified according to hazardous vs. non-hazardous
      alcohol intake (HAU vs. non-HAU) and calcium (Ca) levels by analyzing baseline
      data. The group was chosen to represent relatively "pure" HAU with minimal drug
      use and no psychiatric diagnoses. With these narrow parameters in place, we found
      evidence that HAU significantly increases TNF-alpha levels compared to Non-HAU
      (2.8 +/- 0.6 vs. 1.9 +/- 0.3 pg/ml, p = 0.05) and decreases blood Ca levels (9 +/
      0.6 vs. 9.4 +/- 0.5, p = 0.03). Our analyses also suggest that chronic
      inflammation, as indicated by increased TNF-alpha levels, is associated with
      hypocalcemia (hypoCa <8.6). Despite the limited prevalence of hypoCa, these
      findings are clinically significant given that hypoCA PLWH exhibited decreased
      CD4 (253 +/- 224 vs. 417.7 +/- 281, p = 0.02), B cells (147 +/- 58 vs. 248 +/-
      151, p = 0.03) and NK cells (146.8 +/- 90 vs. 229 +/- 148, p = 0.008) and
      elevated CD8 (902.5 +/- 438 vs. 699 +/- 510, p = 0.09) compared to those with
      normal calcium. Furthermore, calcium effects on viral load were also evident with
      hypoCA exhibiting the highest loads (140,187 +/- 111 vs. 35,622 +/- 7770 HIV
      copies, p = 0.01). Multivariate analyses confirmed the significance of hypoCa in
      predicting viroimmune parameters. This paper provides the first evidence that
      hypoCa accounts for some of the variation in viroimmune measures in HAART
      recipients and suggests that hypoCa may be mediating alcohol's deleterious
      effects.

PMID- 22857858
TI  - Clinical and dosimetric characteristics of temporal lobe injury following
      intensity modulated radiotherapy of nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: To evaluate the temporal lobe injury (TLI) in
      nasopharyngeal carcinoma (NPC) patients who had received intensity modulated
      radiotherapy (IMRT) and to assess the dosimetric parameters associated with TLI.
      MATERIALS AND METHODS: Forty of 870 patients were diagnosed with TLI after IMRT,
      the clinical and dosimetric characteristics of these TLI were analyzed. RESULTS:
      A total of 4.6% (40/870) patients have developed TLI. However, TLI is not
      observed in T1-2 patients, the incidences are 3.1% and 13.4% in T3 and T4
      patients respectively. The Dmax (maximum point dose, Gy) and D1 cc (the dose
      delivered to the 1 cubic centimeter volume, Gy) in injured temporal lobes (TLs)
      are greater than that in normal TLs (P<0.01). TLI is not observed in TLs with
      Dmax<64 Gy or D1 cc<52 Gy, and the 5-year incidence of TLI in patients with Dmax
      64-68 Gy or D1 cc 52-58 Gy is <5.0%. A linear regression demonstrates a 2.6%
      augment of TLI per Gy of Dmax exceeding 64 Gy and a 2.5% augment of TLI per Gy of
      D1 cc exceeding 52 Gy; TLI is correlated with Dmax (r=0.89, P<0.01) and D1 cc
      (r=0.87, P<0.01) respectively. CONCLUSIONS: The incidence of TLI is relatively
      high, especially for patients with advanced T-stage NPC, and correlated with Dmax
      and D1 cc. IMRT with Dmax<68 Gy or D1 cc<58 Gy in TLs is relatively safe.

PMID- 22857857
TI  - Prostate post-implant dosimetry: interobserver variability in seed localisation,
      contouring and fusion.
AB  - AIM: Reliable post-implant evaluation of prostate seed implants requires optimal
      seed identification and accurate delineation of anatomical structures. In this
      study the GEC-ESTRO groups BRAPHYQS and PROBATE investigated the interobserver
      variability in post-implant prostate contouring, seed reconstruction and image
      fusion and its impact on the dose-volume parameters. MATERIALS: Post-implant T2
      TSE, T1-GE and CT images were acquired for three patients, in order to evaluate
      four post-plan techniques: (a) CT, (b) T1+T2, (c) CT+T2, (d) CT+T1(int)+T2. Three
      interobserver studies were set up. (1) Contouring: the CTV-prostate was
      delineated on CT and T2 by eight physicians. Additionally one reference contour
      was defined on both image modalities for each patient. (2) Seed reconstruction:
      seven physicists localised the seeds on T1 and CT, manually and with CT seed
      finder tools. A reference seed geometry was defined on CT and T1. (3) Fusion: six
      physicists registered the image sets for technique (b)-(d), using seeds (if
      visible) and anatomical landmarks. A reference fusion was determined for each
      combined technique. RESULTS: (1) The SD(ref) for contouring (1 SD with respect to
      the reference volume) was largest for CT (23%), but also surprisingly large for
      MRI (17%). This resulted in large SD(ref) values for D90 for all techniques (17
      23%). The surprisingly large SD(ref) for MRI was partly due to variations in
      interpretation of what to include in the prostate contour. (2) The SD(ref) in D90
      for seed reconstruction was small (2%) for all techniques, except for T1+T2 (7%).
      (3) The SD(ref) in D90 due to image fusion was quite large, especially for direct
      fusion of CT+T2 (16%) where clearly corresponding landmarks were missing (seeds
      hardly visible on T2). In general, we observed large differences in D90 depending
      on the technique used. CONCLUSIONS: The dosimetric parameters for prostate post
      implant evaluation showed large technique-dependent interobserver variabilities.
      Contouring and image fusion are the 'weak links' in the procedure. Guidelines and
      training in contouring together with incorporation of automated fusion software
      need to be implemented.

PMID- 22857859
TI  - Three cytotoxic drugs combined with pelvic radiation and as maintenance
      chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): long
      term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and
      cisplatin.
AB  - PURPOSE: Phase III trials in the 1990s for squamous cell carcinoma of the anus
      (SCCA) demonstrated 5-fluorouracil (5FU) and mitomycinC (MMC) chemoradiation
      (CRT) improved outcome compared to radiation (RT) alone, but local recurrence
      remained significant. This prospective pilot study intensified treatment by
      integrating 3 cytotoxic drugs into CRT and maintenance chemotherapy. METHODS: CRT
      comprised 5-FU 1000 mg/m(2) days 1-4,29-32, MMC 10 mg/m(2) day 1 and Cisplatin
      (CDDP) 60 mg/m(2) days1 and 29, with 45 Gy in 25 daily fractions, followed by a
      15 Gy boost. Maintenance chemotherapy started 4-8 weeks later, three courses
      repeated every 21 days, using 5-FU/CDDP doses above, with MMC reduced to 7
      mg/m(2) and administered with the first and third cycles. RESULTS: In CRT only
      14/19 (74%) patients received protocol-defined chemotherapy doses in week 5.
      Compliance to maintenance chemotherapy was poor. 15/19 started cycle 1, 13
      started cycle 2 and 11 cycle 3. 17/19 experienced G3-G5 toxicity (16 Grade 3/4
      and one Grade 5). 16/19 patients (84%) remain alive and disease-free - median
      follow-up 79 months (34-115). CONCLUSIONS: Despite favourable results, the
      significant toxicity and low compliance of the three-drug CRT regimen used,
      deemed it unsuitable for testing in a phase III trial. A two-drug maintenance
      regimen was explored in the ACT II trial.

PMID- 22857860
TI  - Recommendations for CTV margins in radiotherapy planning for non melanoma skin
      cancer.
AB  - PURPOSE: To provide practice guidelines for delineating clinical target volume
      (CTV) for radiotherapy planning of non melanoma (NMSC) skin cancers. METHODS AND
      MATERIALS: A prospective, single arm, study. Preoperatively, a radiation
      oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental
      marks in four directions from the delineated border. Under local anesthesia, the
      lesion was excised, and resection margins were assessed microscopically by frozen
      section. Once resection margins were clear, the microscopic tumor extent was
      calculated using the presurgical incremental markings as references. A potential
      relationship between the distance of microscopic tumor extension and other
      variables was analyzed. RESULTS: A total of 159 lesions in 150 consecutive
      patients, selected for surgical excision with frozen section assisted assessment
      of resection margins, were accrued. The distance of microscopic tumor extension
      beyond a gross lesion varied from 1mm to 15 mm, with a mean of 5.3mm. The
      microscopic tumor extent was positively correlated with the size of gross lesion,
      histology and number of surgical attempts required to obtain a clear margin. To
      provide a 95% or greater chance of covering microscopic disease we make the
      following recommendations for CTV margins; 10mm for BCC less than 2 cm, 13 mm for
      BCC greater than 2 cm, 11 mm for SCC less than 2 cm, and 14 mm for SCC greater
      than 2 cm. CONCLUSIONS: Tumors greater than 2 cm and SCC histology required
      larger margins to adequately cover the microscopic extent of disease. This
      information is crucial in radiation planning of NMSC. Clinicians should be
      cautioned, as these guidelines may not offer optimum treatment for patients with
      extremely large or small lesions.

PMID- 22857861
TI  - Fishing human monoclonal antibodies from a CHO cell supernatant with boronic acid
      magnetic particles.
AB  - In this work we have evaluated the potential of boronic acid functionalized
      magnetic particles for the one-step capture of a human monoclonal antibody (mAb)
      from a Chinese hamster ovary (CHO) cell culture supernatant. For comparison,
      Protein A coated magnetic particles were also used. The most important factor
      influencing the overall process yield and product purity in boronic acid
      particles was found to be the binding pH. Basic pH values promoted higher
      purities while resulting in decreased yields due to the competing effects of
      molecules such as glucose and lactate present in the cell culture supernatant.
      After optimization, the particles were successfully used in a multi-cycle
      purification process of the mAb from the CHO feedstock. Boronic acid particles
      were able to achieve an average overall yield of 86% with 88% removal of CHO host
      cell proteins (HCP) when the binding was performed at pH 7.4, while at pH 8.5
      these values were 58% and 97%, respectively. In both cases, genomic DNA removal
      was in excess of 97%. Comparatively, Protein A particles recorded an average
      overall yield of 80% and an HCP removal greater than 99%. The adsorption of the
      mAb to the boronic acid particles was shown to be mediated by strong affinity
      interactions. Overall, boronic acid based purification processes can offer a cost
      effective alternative to Protein A as the direct capturing step from the
      mammalian cell culture.

PMID- 22857862
TI  - Quantitative profiling of glucosinolates by LC-MS analysis reveals several
      cultivars of cabbage and kale as promising sources of sulforaphane.
AB  - Sulforaphane is an isothiocyanate well known for its potential health benefits.
      With the aim of finding sulforaphane supply sources, its precursor,
      glucoraphanin, was widely searched for among Brassica oleracea varieties.
      Quantitative profiling of seven glucosinolates by LC-MS analysis was performed on
      6 cultivars of broccoli, 32 of cabbage and 24 cultivars of kale. The
      glucoraphanin levels found in three cultivars of cabbage and six cultivars of
      kale were comparable with, or even higher than, the highest of broccoli (119.4
      mg/100g FW). The most promising group belonged to the black kale, Cavolo nero.
      Use of a C30 column and an ammonium formate buffer in LC-MS and a micro plate
      solid phase extraction technique was highly effective.

PMID- 22857863
TI  - Simultaneous measurement of imatinib, nilotinib and dasatinib in dried blood spot
      by ultra high performance liquid chromatography tandem mass spectrometry.
AB  - Imatinib, dasatinib and nilotinib are three tyrosine kinase inhibitors currently
      used to treat Bcr-Abl1 positive chronic myelogenous leukaemia (CML). However,
      achieving maximum benefit with these drugs may require optimal dosing and
      adherence to therapy. In those cases, therapeutic drug monitoring (TDM) can be a
      useful tool in managing patients with CML. The paper presents simple and high
      throughput method for simultaneous determination of all three TKIs in dried blood
      spot (DBS) samples from CML patients. DBS samples were prepared by applying 10
      MUL of spiked whole blood onto an Agilent DBS cards. Whole blood spot was punched
      out of the card, transferred to a well in a 96-well Captiva ND Lipids filter
      plate. After the addition of isotopically labelled internal standard, the drug
      was extracted with 0.1% formic acid in methanol. The collected extract (1 MUL)
      was injected onto a Phenomenex Kinetex 50 mm * 2.1 mm C18 column and eluted with
      acetonitrile gradient into a triple quadrupole ESI-MS/MS Agilent 6460 operated in
      positive mode. The total run time was only 2.6 min. The method was validated in
      terms of linearity, selectivity, specificity, accuracy, precision, absolute and
      relative matrix effect and stability. The effect of haematocrit (Hct) on the
      accurate concentration determination was also examined. The method was linear in
      the range of 50-5000 MUg/L for imatinib and nilotinib and in the range of 2.5-250
      MUg/L for dasatinib, with correlation coefficient values higher than 0.997. Lower
      limits of quantification (LLOQ) were 50 MUg/L for imatinib and nilotinib and 2.5
      MUg/L for dasatinib. The method proved to be accurate (% bias < 13.2) and precise
      (CV < 10.3%) on intra- as well as on inter-day basis. Sample matrix (% ME=94.5
      106.7) and different Hct values had no significant effect on the accuracy of
      measured concentrations. Samples proved to be stable whilst stored on DBS cards
      at room temperature or in the refrigerator; however, at 40  degrees C the
      stability of dasatinib was compromised. The method presented was successfully
      applied to clinical samples.

PMID- 22857864
TI  - A stable isotope dilution LC-ESI-MS/MS method for the quantification of pyridoxal
      5'-phosphate in whole blood.
AB  - Vitamin B6 is a cofactor in numerous biologic processes that include
      gluconeogenesis, neurotransmitter synthesis and amino acid metabolism. The aim of
      this study was to develop a method to measure the concentration of the
      biologically active form of vitamin B6 (pyridoxal-5'-phosphate, PLP) in whole
      blood with stable isotope dilution LC-ESI-MS/MS and compare this new procedure
      with an established HPLC method based on derivatization of pyridoxal-5'
      phosphate. 50 MUl of stable isotope (PLP-d3) was added to 250 MUl of sample,
      followed by deproteinization with 10% trichloroacetic acid. After centrifugation,
      20 MUl of the supernatant was injected into the LC-ESI-MS/MS. Reversed phase
      chromatography was performed on a UPLC system, using a WatersTM Symmetry C18
      column, with a gradient of 0.1% formic acid in methanol. PLP was measured on a
      tandem MS with a mass transition of 247.8>149.8 in the positive ion mode with a
      collision energy of 14 eV. The chromatographic run lasted 4 min. The method was
      linear from 4 to 8000 nmol/l. The intra-day and inter-day precision ranged
      between 1.7-2.8% and 3.0-4.1%, respectively. The mean absolute matrix-effect was
      99.3% [97-102%]. The relative matrix-effect was 98.8%. The mean recovery was 98%
      [89-103%]. The lower limit of quantification was 4 nmol/l. The comparison of the
      LC-ESI-MS/MS method with our current HPLC method yielded the following equation:
      LC-ESI-MS/MS=1.11 [confidence interval, CI: 1.03-1.20] * HPLC+4.6 [CI: -1.3 to
      11.0] (r2=0.94). This LC-ESI-MS/MS based method is characterized by simple sample
      processing and a short run time. The comparison with the current HPLC method is
      excellent although a significant proportional bias was detected. To conclude, the
      LC-ESI-MS/MS method is an appropriate method to determine PLP in whole blood.

PMID- 22857865
TI  - Measurement of bone mineral density in the tunnel regions for anterior cruciate
      ligament reconstruction by dual-energy X-ray absorptiometry, computed tomography
      scan, and the immersion technique based on Archimedes' principle.
AB  - PURPOSE: To determine, for anterior cruciate ligament (ACL) reconstruction,
      whether the bone mineral density (BMD) of the femoral tunnel was higher than that
      of the tibial tunnel, to provide objective evidence for choosing the appropriate
      diameter of interference screws. METHODS: Two groups were enrolled. One group
      comprised 30 normal volunteers, and the other comprised 9 patients with ACL
      rupture. Dual-energy X-ray absorptiometry was used to measure the BMD of the
      femoral and tibial tunnel regions of the volunteers' right knees by choosing a
      circular area covering the screw fixation region. The knees were also scanned by
      spiral computed tomography (CT), and the 3-dimensional reconstruction technique
      was used to determine the circular sections passing through the longitudinal axis
      of the femoral and tibial tunnels. Grayscale CT values of the cross-sectional
      area were measured. Cylindrical cancellous bone blocks were removed from the
      femoral and tibial tunnels during the ACL reconstruction for the patients. The
      volumetric BMD of the bone blocks was measured using a standardized immersion
      technique according to Archimedes' principle. RESULTS: As measured by dual-energy
      X-ray absorptiometry, the BMD of the femoral and tibial tunnel regions was 1.162
      +/- 0.034 g/cm(2) and 0.814 +/- 0.038 g/cm(2), respectively (P < .01). The CT
      value of the femoral tunnel region was 211.7 +/- 11.5 Hounsfield units, and the
      value of the tibial tunnel region was 104.9 +/- 7.4 Hounsfield units (P < .01).
      The volumetric BMD of the bone block from the femoral tunnel (2.80 +/- 0.88
      g/cm(3)) was higher than the value from the tibial tunnel (1.88 +/- 0.59 g/cm(3))
      (P < .01). Comparing the data between male and female patients, we found no
      significant difference in both femoral and tibial tunnel regions. CONCLUSIONS:
      For ACL reconstruction, the BMD of the femoral tunnel is higher than that of the
      tibial tunnel. This implies that a proportionally larger-diameter interference
      screw should be used for fixation in the proximal tibia than that used for
      fixation in the distal femur. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 22857866
TI  - [Methimazole-induced liver injury].

PMID- 22857867
TI  - Association between SIRT2 gene polymorphism and height in healthy, elderly
      Japanese subjects.

PMID- 22857869
TI  - MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.
AB  - Conventional clinical parameters are not sensitive or specific enough for
      detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE).
      Measurement of cytokines in urine is an encouraging approach to detection of
      early flares in this disease. Here we have profiled 27 different cytokines,
      chemokines and celular growth factors in the urine of 48 patients previously
      diagnosed of SLE as potential biomarkers of disease activity. Correlation
      analysis with Bonferroni correction showed that MCP-1 was the only immune
      mediator which levels in urine correlated directly with the SLE Disease Activity
      Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003).
      MCP-1 correlated inversely with levels of C3 complement protein in serum (
      0.50,0.001). MCP-1 showed significant higher levels in patients with severe
      disease activity in comparison with those exhibiting mild activity. Levels of
      this chemokine were also higher in patients with severe disease activity in
      comparison with patients with inactive disease and healthy controls. Areas under
      receiver operating characteristic curves (AUROC) for detection of severe disease
      (SLEDAI?8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96)
      0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for
      detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis
      were repeated excluding those patients with active renal disease (n=14), levels
      of MCP-1 in urine kept on showing a significant positive association with SLEDAI
      2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated
      the superiority of MCP-1 over a wide range of cytokines as biomarker of disease
      activity in SLE.

PMID- 22857868
TI  - Umbilical artery chemokine CCL16 is associated with preterm preeclampsia and
      fetal growth restriction.
AB  - BACKGROUND: Cytokines and growth factors synthesized by placental trophoblasts
      are suggested to induce endothelial and vascular smooth muscle cell apoptosis and
      affect angiogenesis. OBJECTIVE: To investigate cord blood and placental
      immunoproteins in order to find new clues on pathogenetic factors of preterm
      preeclampsia. METHODS: Cord blood samples were collected on 163 consecutive
      preterm deliveries prior to 32 gestational weeks. Placental function, clinical
      risk factors and 107 umbilical artery immunoproteins were analyzed.
      Classification and regression trees analysis was used to detect associations
      between the immunoproteins, clinical parameters and preterm preeclampsia.
      Placental expression of the immunoproteins and their receptors were subsequently
      investigated. RESULTS: Preeclampsia complicated 34% of the pregnancies in this
      preterm cohort. Umbilical artery CCL16, CCL24, and CCL23 were associated with
      preeclampsia, CCL16 showing the strongest relationship with an OR (95% CI) of
      24.5 (5.4-112.0). High umbilical artery CCL16 was also characteristic to fetuses
      with severe growth restriction (<3rd percentile). CCL16, CCL24 and their
      receptors, CCR1 and CCR3 were expressed in preeclamptic placentas. CONCLUSIONS:
      High umbilical artery CCL16 is prominently detected in preterm preeclamptic
      pregnancies with severe growth restriction. A link to compensatory proangiogenic
      mechanisms has to be considered.

PMID- 22857870
TI  - An examination of wilderness first aid knowledge, self-efficacy, and skill
      retention.
AB  - OBJECTIVE: The purpose of this study was to examine the retention of wilderness
      first aid (WFA) knowledge, self-efficacy beliefs, and skills over time in a
      sample of WFA course participants. METHODS: Seventy-two open enrollment
      (volunteer) WFA course participants were assessed at 4 months, 8 months, or 12
      months after training. Changes in WFA knowledge and self-efficacy were assessed
      by written instruments after the course and at the follow-up interval (4, 8, or
      12 months). The WFA skills were assessed by a scored medical scenario at the
      follow-up interval. RESULTS: As the time interval increased, WFA knowledge, self
      efficacy, and skill proficiency decreased. The WFA knowledge and self-efficacy
      beliefs were not highly correlated with skill performance. CONCLUSIONS: Without
      additional training, regular use of the course content, or efforts to refresh
      thinking on key topics, the ability of WFA students to effectively apply their
      learning will likely decrease as time from training increases. With respect to
      these WFA courses, student scores on written tests did not accurately reflect
      competence in performing practical skills related to a medical scenario. In
      addition, student self-confidence in the ability to perform such skills did not
      strongly correlate with actual skills and ability.

PMID- 22857871
TI  - Peculiar charging effects on titania in aqueous 1:1, 2:1, 1:2 and mixed
      electrolyte suspensions.
AB  - Charging of particles in aqueous suspensions is primarily related to potential
      determining ions, such as silver and iodide ions at silver halide particle
      surfaces. Proton is considered as a (secondary) potential determining ion at
      hydrated metal oxide surfaces. Indifferent electrolytes neutralize at increased
      concentration the surface charge but do not reverse it. However, in the presence
      of a non-Coulombic interaction the surface charge may be enhanced or reversed at
      increased ionic strength. Such interaction is denoted specific which may be due
      to enhanced van der Waals dipolar, Lewis acid-base, solvation (Hofmeister) and/or
      Born solvation effects. Alternatively, these interactions have been characterized
      in terms of (semi) empirical ion and surface properties, such as hard-soft acid
      base (HSAB) interaction. Within the Stern layer closest to the particle surface
      truly specific effects are related to the inner Helmholtz plane (IHP) in order to
      distinguish them from the charge and solvation related effects occurring within
      the outer Helmholtz plane (OHP). We review some recent observations on the
      particular influence of ions on the charging of titania particles in aqueous 1:1,
      2:1, 1:2 and mixed electrolyte suspensions.

PMID- 22857872
TI  - The role of total hip replacement in the treatment of displaced intracapsular hip
      fractures in the elderly.

PMID- 22857873
TI  - Evaluation of constipation after parasacral transcutaneous electrical nerve
      stimulation in children with lower urinary tract dysfunction--a pilot study.
AB  - OBJECTIVE: To evaluate the efficacy of parasacral transcutaneous electrical nerve
      stimulation (TENS) for the treatment of constipation in children with lower
      urinary tract dysfunction (LUTD). MATERIALS AND METHODS: We treated 9 boys and 5
      girls with a mean age of 8.07 +/- 2.72 years. 10 (71.4%) had overactive bladder
      and 4 (28.6%) had voiding dysfunction. A total of 20 parasacral TENS sessions, 20
      min each (10 Hz), were performed 3 times per week. The criteria used to assess
      constipation were the Rome III criteria for children, the Bristol Stool Chart,
      and a visual analog scale (pain from 0 to 10). The children were reassessed
      immediately after treatment. No specific treatment of constipation was performed.
      RESULTS: After treatment, 85.7% (p < 0.001) of the children's constipation
      symptoms had improved following the Rome III criteria. Parasacral TENS
      significantly impacted the following symptoms: "the presence of at least one
      episode of fecal incontinence per week", "history of stool retention", and "the
      presence of a large fecal mass in the rectum." There was no significant change in
      the Bristol Stool Chart evaluation (p < 0.25), but there was a significant
      improving trend in level of pain before and after treatment (p < 0.063). All
      urinary symptoms evaluated showed improvement after TENS treatment. There was a
      decrease in post-void residual urine. CONCLUSION: In this first study to evaluate
      the results of parasacral TENS on constipation in children with LUTD,
      satisfactory results were obtained for both complaints.

PMID- 22857874
TI  - As always we are very grateful to all of you who act as reviewers of submitted
      articles to the journal. Introduction.

PMID- 22857875
TI  - Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in comatose
      survivors of cardiac arrest: characteristics and prognostic value.
AB  - OBJECTIVES: To analyze the prevalence of stimulus-induced rhythmic, periodic or
      ictal discharges (SIRPIDs) in patients with coma after cardiac arrest (CA) and
      therapeutic hypothermia (TH) and to examine their potential association with
      outcome. METHODS: We studied our prospective cohort of adult survivors of CA
      treated with TH, assessing SIRPIDs occurrence and their association with 3-month
      outcome. Only univariated analyses were performed. RESULTS: 105 patients with
      coma after CA who underwent electroencephalogram (EEG) during TH and normothermia
      (NT) were studied. Fifty-nine patients (56%) survived, and 48 (46%) had good
      neurological recovery. The prevalence of SIRPIDs was 13.3% (14/105 patients), of
      whom 6 occurred during TH (all died), and 8 in NT (3 survived, 1 with good
      neurological outcome); none had SIRPIDs at both time-points. SIRPIDs were
      associated with discontinuous or non-reactive EEG background and were a robustly
      related to poor neurological outcome (p < 0.001). CONCLUSION: This small series
      provides preliminary univariate evidence that in patients with coma after CA,
      SIRPIDs are associated with poor outcome, particularly when occurring during in
      therapeutic hypothermia. However, survival with good neurological recovery may be
      observed when SIRPIDs arise in the post-rewarming normothermic phase.
      SIGNIFICANCE: This study provides clinicians with new information regarding the
      SIRPIDs prognostic role in patients with coma after cardiac arrest.

PMID- 22857876
TI  - Blink reflex prepulse inhibition and excitability recovery: influence of age and
      sex.
AB  - OBJECTIVE: Age and sex affect various reflexes in healthy humans. Their
      respective influence on prepulse inhibition (PPI) of the trigeminofacial blink
      reflex (BR) and BR excitability recovery has not as yet been investigated in
      detail. METHODS: We studied the trigeminofacial BR bilaterally in 62 healthy
      volunteers (31 males, age 41.0 +/- 13.2 years, mean +/- SD, 31 females, 39.2 +/-
      11.7 years) following right supraorbital nerve stimulation. Single sweeps were
      recorded either alone (n = 8) or conditioned by a prepulse applied 100 ms earlier
      to the dominant index finger though ring electrodes (n = 8). Latency and
      amplitude of the ipsilateral R1 component, as well as latency and area-under-the
      curve of the ipsilateral R2 and contralateral R2c components were measured in
      single traces and then averaged per subject. BR excitability recovery was
      established bilaterally following right supraorbital nerve stimulation with
      paired pulses. Six responses were averaged on-line per interstimulus interval
      (ISI 160, 300, and 500 ms). RESULTS: Unconditioned BR did not differ
      significantly between males and females, but R2 and R2c latencies increased with
      age. Prepulse stimulation caused significant facilitation of R1 (latency and
      amplitude), and inhibition of R2 and R2c (latency and area), irrespective of age.
      PPI of R2 and R2c area was significantly more pronounced in men. BR excitability
      recovery was significantly influenced by age, but not by sex. Multiple regression
      showed inverse correlation of age with conditioned R2 and R2c area at ISI 300 ms
      and 500 ms (P < 0.01 each), indicating reduced excitability recovery. No
      parameter showed significant interaction of age * sex. CONCLUSION: These data
      indicate less pronounced PPI of the trigeminofacial BR in females, concurring
      with previous reports of sex differences in protective reflexes, but also
      suggesting less rigorous filtering of information flow to the brain in females.
      Reduced BR excitability to paired-pulse stimulation may counteract age-related
      disinhibition of brainstem interneuronal circuitry. SIGNIFICANCE: The present
      findings allow new insight into human brainstem physiology.

PMID- 22857877
TI  - Diametral compression test with composite disk for dentin bond strength
      measurement--finite element analysis.
AB  - OBJECTIVE: A novel technique using a composite disk under diametral compression
      was presented in a previous study for measuring the bond strength between
      intracanal posts and dentin. This study deals with the stress distribution within
      the composite disk to allow the bond strength to be calculated accurately. The
      effects of changing geometrical and material parameters on the post-dentin
      interfacial stress are also evaluated. METHODS: The finite element method with 3D
      models is used to analyze the stress distribution and to carry out the
      sensitivity analysis. Progressive post-dentin interfacial debonding is also
      simulated to better understand the failure process observed in experiments.
      RESULTS: Material mismatch causes stress concentrations at the interfaces. The
      results are presented as correction factors to be used in conjunction with the
      analytical solution for a homogeneous disk. Comparison between the stresses at
      the post-dentin interface and those in dentin confirms that interfacial debonding
      will take place prior to fracture in the dentin. SIGNIFICANCE: The numerical
      solutions presented here will facilitate the adoption of the composite disk in
      diametral compression for bond strength measurement.

PMID- 22857881
TI  - Effect of anti-inflammatory supplementation with whey peptide and exercise
      therapy in patients with COPD.
AB  - BACKGROUND: One of the major pathophysiologies in advanced chronic obstructive
      pulmonary disease (COPD) has been attributed to systemic inflammation. Meta
      analysis of the 2005 Cochrane Database concluded the effect of nutritional
      supplementation alone on stable COPD was insufficient to promote body weight gain
      or exercise capacity. The aim of this study was to investigate the effectiveness
      of nutritional supplementation therapy using a nutritional supplement containing
      whey peptide with low-intensity exercise therapy in stable elderly patients with
      COPD. METHOD: In stable elderly COPD patients with %IBW and %FEV(1) of less than
      110 and 80%, respectively, anti-inflammatory nutritional supplementation therapy
      was added to low-intensity exercise therapy. Thirty-six COPD patients were
      divided into those with and those without the ingestion of an anti-inflammatory
      nutritional supplement containing whey peptide, which exhibited an anti
      inflammatory effect. These two groups were designated as the nutritional support
      and the control groups, respectively. The body composition, skeletal muscle
      strength, exercise tolerance, health-related QOL (HRQOL), and inflammatory
      cytokines were evaluated before and three months after nutritional support
      combined with exercise therapy in both the nutritional support group and the
      control group. RESULTS: In the nutritional support group, the body weight, %IBW,
      FM, energy intake, %AC, Alb, PImax, PEmax, 6MWD, WBI, emotional function, and CRQ
      total were significantly increased, and the levels of hsCRP, IL-6, IL-8, and TNF
      alpha were reduced significantly, while no significant change was noted in any
      item of physiological evaluation or any biomarker in the control group.
      CONCLUSION: Concomitant use of a anti-inflammatory nutritional supplement
      containing whey peptide, which exhibits an anti-inflammatory effect, with
      exercise therapy in stable elderly COPD patients with %IBW<110% and %FEV(1)<80%
      may not only increase body weight but may also inhibit systemic inflammation and
      thus improve exercise tolerance and HRQOL.

PMID- 22857882
TI  - Chronic kidney disease predicts poor prognosis in patients with stable premature
      coronary artery disease.
AB  - OBJECTIVE: This study was performed to determine the prevalence of chronic kidney
      disease (CKD) as well as its association with mid-term prognosis in patients with
      stable premature coronary artery disease (CAD) in a Chinese population. METHODS:
      Five hundred and twelve patients from Jiangsu Province, China with stable,
      premature CAD were enrolled using an estimated glomerular filtration rate (eGFR)
      to determine the presence of CKD. The patients were then monitored over a two
      year follow up during which major adverse cardiac events (MACEs) were recorded
      and analyzed. RESULTS: One hundred and eighty-three patients (35.74%) were
      determined to have CKD. Having CKD was associated with a higher ratio of type 2
      diabetes mellitus, multi-vessel disease, higher levels of fasting blood sugar and
      lower levels of left ventricular ejection fraction (all P<0.05). Patients with
      CKD had significantly higher incidences of composite MACEs than the non-CKD group
      at the end of the two- (45.35% vs 30.72%, P=0.001) but not one-year follow up
      (30.64% vs 25.32%, P=0.209). Furthermore, as eGFR decreased, more MACEs occurred
      (all P<0.05). Multivariate analysis confirmed that both CKD (P<0.001) and multi
      vessel disease (P<0.001) are independent risk factors for MACEs. CONCLUSION:
      Chinese patients diagnosed with stable, premature CAD and CKD have more risk
      factors and worse two-year outcomes than those with only CAD.

PMID- 22857879
TI  - Periostin is a systemic biomarker of eosinophilic airway inflammation in
      asthmatic patients.
AB  - BACKGROUND: Eosinophilic airway inflammation is heterogeneous in asthmatic
      patients. We recently described a distinct subtype of asthma defined by the
      expression of genes inducible by T(H)2 cytokines in bronchial epithelium. This
      gene signature, which includes periostin, is present in approximately half of
      asthmatic patients and correlates with eosinophilic airway inflammation. However,
      identification of this subtype depends on invasive airway sampling, and hence
      noninvasive biomarkers of this phenotype are desirable. OBJECTIVE: We sought to
      identify systemic biomarkers of eosinophilic airway inflammation in asthmatic
      patients. METHODS: We measured fraction of exhaled nitric oxide (Feno),
      peripheral blood eosinophil, periostin, YKL-40, and IgE levels and compared these
      biomarkers with airway eosinophilia in asthmatic patients. RESULTS: We collected
      sputum, performed bronchoscopy, and matched peripheral blood samples from 67
      asthmatic patients who remained symptomatic despite maximal inhaled
      corticosteroid treatment (mean FEV(1), 60% of predicted value; mean Asthma
      Control Questionnaire [ACQ] score, 2.7). Serum periostin levels are significantly
      increased in asthmatic patients with evidence of eosinophilic airway inflammation
      relative to those with minimal eosinophilic airway inflammation. A logistic
      regression model, including sex, age, body mass index, IgE levels, blood
      eosinophil numbers, Feno levels, and serum periostin levels, in 59 patients with
      severe asthma showed that, of these indices, the serum periostin level was the
      single best predictor of airway eosinophilia (P = .007). CONCLUSION: Periostin is
      a systemic biomarker of airway eosinophilia in asthmatic patients and has
      potential utility in patient selection for emerging asthma therapeutics targeting
      T(H)2 inflammation.

PMID- 22857883
TI  - Anxiety, personality traits and quality of life in functional dyspepsia-suffering
      patients.
AB  - BACKGROUND: Psychosocial stressors either acute or more sustained frequently
      precede the onset and exacerbation of the symptoms of the functional dyspepsia
      (FD). Depressive mood and quality of life have been already reported for
      interference in functional dyspepsia suffering patients. METHODS: The examination
      were performed on 60 FD patients (30 females and 30 males), aged 20-79 years, 60
      peptic ulcer subjects and 60 healthy volunteers in which we have investigate
      levels of anxiety and depression, personality traits and quality of life. RESULT:
      According to the Hamilton Depression and Anxiety Rating Scales, the population
      with FD had the average score which classified them into the group of patients
      with the moderate depression (20.57 +/- 4.45). Personality traits estimation
      based on data obtained by the Eysenck personality questionnaire revealed higher
      neuroticism scores in the group with functional dyspepsia. Both parameters, level
      of the neuroticism and anxiety level, expressed highly significant level of
      mutual concordance. Patients with functional dyspepsia reported a greater adverse
      impact of symptoms of emotional distress and food and drink problems. CONCLUSION:
      Results are indicating that the depression and anxiety level is the highest in
      patients with functional dyspepsia and that anxiety level corroborates with the
      neuroticism level from the Eysenck scale. Psychological disturbances are
      influencing the quality of life mostly in patients with dyspepsia in the form of
      emotional distress and the problem with the food and beverage intake.

PMID- 22857878
TI  - Polydrug abuse: a review of opioid and benzodiazepine combination use.
AB  - This paper reviews studies examining the pharmacological interactions and
      epidemiology of the combined use of opioids and benzodiazepines (BZDs). A search
      of English language publications from 1970 to 2012 was conducted using PubMed and
      PsycINFO((r)). Our search found approximately 200 articles appropriate for
      inclusion in this paper. While numerous reports indicate that the co-abuse of
      opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of
      these medications are not entirely clear. Though the possibility remains that
      opioid abusers are using BZDs therapeutically to self-medicate anxiety, mania or
      insomnia, the data reviewed in this paper suggest that BZD use is primarily
      recreational. For example, co-users report seeking BZD prescriptions for the
      purpose of enhancing opioid intoxication or "high," and use doses that exceed the
      therapeutic range. Since there are few clinical studies investigating the
      pharmacological interaction and abuse liability of their combined use, this
      hypothesis has not been extensively evaluated in clinical settings. As such, our
      analysis encourages further systematic investigation of BZD abuse among opioid
      abusers. The co-abuse of BZDs and opioids is substantial and has negative
      consequences for general health, overdose lethality, and treatment outcome.
      Physicians should address this important and underappreciated problem with more
      cautious prescribing practices, and increased vigilance for abusive patterns of
      use.

PMID- 22857884
TI  - The risk of sporadic colorectal cancer development is not influenced by fat mass
      and obesity related gene polymorphism in Slavs.

PMID- 22857885
TI  - Enteral feeding tubes in patients undergoing definitive chemoradiation therapy
      for head-and-neck cancer: a critical review.
AB  - Definitive chemoradiation therapy has evolved as the preferred organ preservation
      strategy in the treatment of locally advanced head-and-neck cancer (LA-HNC). Dry
      mouth and dysphagia are among the most common and most debilitating treatment
      related toxicities that frequently necessitate the placement of enteral feeding
      tubes (FT) in these patients to help them meet their nutritional requirements.
      The use of either a percutaneous endoscopic gastrostomy tube or a nasogastric
      tube, the choice of using a prophylactic vs a reactive approach, and the effects
      of FTs on weight loss, hospitalization, quality of life, and long-term functional
      outcomes are areas of continued controversy. Considerable variations in practice
      patterns exist in the United States and abroad. This critical review synthesizes
      the current data for the use of enteral FTs in this patient population and
      clarifies the relative advantages of different types of FTs and the timing of
      their use. Recent developments in the biologic understanding and treatment
      approaches for LA-HNC appear to be favorably impacting the frequency and severity
      of treatment-related dysphagia and may reduce the need for enteral tube feeding
      in the future.

PMID- 22857886
TI  - Effect of body mass index on intrafraction prostate displacement monitored by
      real-time electromagnetic tracking.
AB  - PURPOSE: To evaluate, using real-time monitoring of implanted radiofrequency
      transponders, the intrafraction prostate displacement of patients as a function
      of body mass index (BMI). METHODS AND MATERIALS: The motions of Beacon
      radiofrequency transponders (Calypso Medical Technologies, Seattle, WA) implanted
      in the prostate glands of 66 men were monitored throughout the course of
      intensity modulated radiation therapy. Data were acquired at 10 Hz from setup to
      the end of treatment, but only the 1.7 million data points with a "beam on" tag
      were used in the analysis. There were 21 obese patients, with BMI >= 30 and 45
      nonobese patients in the study. RESULTS: Mean displacements were least in the
      left-right lateral direction (0.56 +/- 0.24 mm) and approximately twice that
      magnitude in the superior-inferior and anterior-posterior directions. The net
      vector displacement was larger still, 1.95 +/- 0.47 mm. Stratified by BMI cohort,
      the mean displacements per patient in the 3 Cartesian axes as well as the net
      vector for patients with BMI >= 30 were slightly less (<0.2 mm) but not
      significantly different than the corresponding values for patients with lower
      BMIs. As a surrogate for the magnitude of oscillatory noise, the standard
      deviation for displacements in all measured planes showed no significant
      differences in the prostate positional variability between the lower and higher
      BMI groups. Histograms of prostate displacements showed a lower frequency of
      large displacements in obese patients, and there were no significant differences
      in short-term and long-term velocity distributions. CONCLUSIONS: After patients
      were positioned accurately using implanted radiofrequency transponders, the
      intrafractional displacements in the lateral, superior-inferior, and anterior
      posterior directions as well as the net vector displacements were smaller, but
      not significantly so, for obese men than for those with lower BMI.

PMID- 22857887
TI  - The impact of local and regional disease extent on overall survival in patients
      with advanced stage IIIB/IV non-small cell lung carcinoma.
AB  - PURPOSE: Patients with advanced stage IIIB or stage IV non-small cell lung
      carcinoma are typically treated with initial platinum-based chemotherapy. A
      variety of factors (eg, performance status, gender, age, histology, weight loss,
      and smoking history) are generally accepted as predictors of overall survival.
      Because uncontrolled pulmonary disease constitutes a major cause of death in
      these patients, we hypothesized that clinical and radiographic factors related to
      intrathoracic disease at diagnosis may be prognostically significant in addition
      to conventional factors. The results have implications regarding the selection of
      patients for whom palliative thoracic radiation therapy may be of most benefit.
      METHODS AND MATERIALS: We conducted a pooled analysis of 189 patients enrolled at
      a single institution into 9 prospective phase II and III clinical trials
      involving first-line, platinum-based chemotherapy. Baseline clinical and
      radiographic characteristics before trial enrollment were analyzed as possible
      predictors for subsequent overall survival. To assess the relationship between
      anatomic location and volume of disease within the thorax and its effect on
      survival, the pre-enrollment computed tomography images were also analyzed by
      contouring central and peripheral intrapulmonary disease. RESULTS: On univariate
      survival analysis, multiple pulmonary-related factors were significantly
      associated with worse overall survival, including pulmonary symptoms at
      presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and
      evidence of obstruction of major bronchi or vessels on prechemotherapy computed
      tomography (P<.0001). When partitioned into central and peripheral volumes,
      central (P<.0001) but not peripheral (P=.74) disease was associated with worse
      survival. On multivariate analysis with known factors, pulmonary symptoms (hazard
      ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and
      bronchial/vascular compression (hazard ratio, 1.54; P=.022) remained significant.
      CONCLUSIONS: Patients with bulky central disease, bronchial/vascular compression,
      and/or pulmonary symptoms exhibited worse overall survival after first-line,
      platinum-based chemotherapy. A subset of these patients may be studied to
      determine whether early, planned palliative thoracic radiation could also be of
      benefit.

PMID- 22857888
TI  - Latest update on the primary Sjogren's syndrome.

PMID- 22857889
TI  - Posterior approach for surgical treatment of neglected elbow dislocation.
AB  - INTRODUCTION: Neglected elbow dislocations often result in contracture and
      functional impairment. Surgical treatment is challenging because of the
      accompanying triceps retraction. We wanted to share our experience in treating
      these neglected dislocations using the posterior approach. PATIENTS AND METHODS:
      This was a consecutive, prospective study over a 4.5-year period (January 2003 to
      June 2007) that included all the patients who presented with a neglected elbow
      dislocation that was older than 21 days. We treated 22 patients (17 men, five
      women) with an average age of 22.8+/-8.2 years (range 14 to 46 years). The
      dislocations were 8.5+/-4.2 months old on average (range 2 to 17 months). Average
      elbow flexion was 46.0 degrees +/-25.9 degrees  (10 degrees  to 90 degrees ) and
      the extension deficit was 19.5 degrees +/-18.4 degrees  (0 degrees  to 60 degrees
      ) before the surgery. A paratricipital approach was used in all patients. In 14
      patients, the dislocation was reduced without triceps lengthening. In eight
      patients, a V-Y plasty of the triceps muscle was required. RESULTS: The average
      follow-up was 21 months (range 12 to 30 months). The improvement in the overall
      range of motion was statistically significant. Average elbow flexion was 112.7
      degrees +/-13.3 degrees  (60 degrees  to 130 degrees ) and the extension deficit
      was 26.6 degrees +/-17.0 degrees  (0 degrees  to 60 degrees ). The average Mayo
      Clinic Elbow Performance Index score was 86 (range 50 to 100), with 14 excellent,
      four good, two average and two poor results. Complications included three cases
      of ulnar nerve paresis, which subsided within three months, and one case of
      superficial infection. DISCUSSION: Although surgical treatment is challenging,
      the functional improvement in neglected elbow dislocations is outstanding. The
      best functional results can be expected when the triceps splitting approach to
      the elbow is not used. LEVEL OF EVIDENCE: IV.

PMID- 22857890
TI  - Patient information ahead of anterior cruciate ligament reconstruction:
      Experience in a university hospital center.
AB  - INTRODUCTION: Patient information is the requisite first step in securing
      informed consent ahead of surgery, and is legally mandatory. The study hypothesis
      was that this information is deficient in a significant proportion of cases. This
      was tested on a clinical audit. The principal objective was to quantify the rate
      of correct patient information communication. The secondary objectives were to
      assess the quality of the information provided by the physician as compared to
      other sources, and to assess the resultant patient satisfaction. MATERIALS AND
      METHODS: A targeted clinical audit included all patients undergoing isolated
      anterior cruciate ligament (ACL) reconstruction in 2009 and 2010. The information
      provided was analyzed from emergency admission through to the specialized
      orthopedic consultation, where all information should in principle be traceable
      in the patient's file. Concordance with information gleaned by the patient
      himself/herself was also assessed. RESULTS: Seventy of the 93 patients recruited
      responded to the study questionnaire (75%). Forty-two had received primary care
      in the Emergency Department, where 67% had been informed about the ACL tear.
      Surgery-related information could be traced in 61% of cases; surgery had been
      discussed in the Emergency Department itself in half of the cases, but only 16%
      had been informed of the duration of the interruption of sports activity and 21%
      of the duration of time off work and the need for early rehabilitation. Following
      the orthopedic consultation, 100% of patients knew that they had an ACL tear, but
      surgery had been spelled out in detail for only 80%, complications for 70%,
      foreseeable outcome for 30%, rehabilitation for 20% and time off work for 60%.
      Thirty-eight patients had retrieved information from the Internet; concordance
      with hospital information was rated at 5.6/10 for the Emergency Department and
      7.5/10 for the orthopedic consultation. DISCUSSION: The quality of patient
      information remains deficient. Traceability of information in the patient's file
      was only 61%. In the Emergency Department, information comprised diagnosis and
      referral to specialist consultation. In the orthopedic consultation, information
      focused on surgical procedure more than on postoperative course. Family doctors
      and physical therapists also have a role to play, but other sources, such as
      validated brochures including recommended web-sites, could improve patient
      information. LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 22857891
TI  - Geometrical analysis results of 42 resurfacing shoulder prostheses: A CT scan
      study.
AB  - BACKGROUND: Shoulder resurfacing arthroplasty was introduced in Scandinavia in
      the early 1980s then developed by SA Copeland. HYPOTHESIS: Resurfacing prostheses
      restore the normal anatomy of the proximal humerus. Here, our objective was to
      evaluate humeral resurfacing prosthesis position on radiographs and computed
      tomography (CT) images. MATERIALS AND METHODS: We retrospectively reviewed 42
      consecutive cases seen at a single centre between 2004 and 2009. Mean patient age
      was 65 years. CT was performed routinely before prosthesis implantation and at re
      evaluation. The Copeland Mark III((r)) (Biomet France SARL, 26903 Valence,
      France) implant was used in 32 cases and the Aequalis Resurfacing Head((r))
      (Tornier France, 38334 Saint-Ismier, France) in 10 cases. The post-implantation
      CT images were used to measure the angle of inclination, medial humeral offset,
      lateral glenohumeral offset, and version of the implant. RESULTS: Mean follow-up
      was 18 months. Compared to baseline, no significant changes were found at re
      evaluation for the angle of inclination or lateral glenohumeral offset. In
      contrast, medial humeral offset increased by 3.47mm, and excessive anteversion of
      4.23 degrees  compared to the bicondylar line was noted. DISCUSSION: Humeral head
      resurfacing prostheses restore the overall anatomy of the proximal humeral head.
      Our CT scan evaluation protocol seems reproducible and enables an evaluation of
      implant geometry. In our experience, resurfacing arthroplasty restored the native
      humeral offset. Inadequate retroversion was noted and was probably related to
      insufficient exposure during surgery. LEVEL OF EVIDENCE: Level IV, retrospective
      study.

PMID- 22857892
TI  - Involvement of lipooligosaccharide heptose residues of Haemophilus parasuis SC096
      strain in serum resistance, adhesion and invasion.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease. To investigate
      the role of lipooligosaccharide (LOS) in H. parasuis infection, DeltaopsX,
      DeltarfaF and DeltawaaQ mutants defective in expressing opsX, rfaF and waaQ
      heptosyltransferases were constructed by transformation. Compared to the wild
      type SC096 strain, the DeltaopsX and DeltarfaF mutants, but not the DeltawaaQ
      mutant, produced severely truncated LOS. The mutants exhibited various degrees of
      reduction in resistance to complement-mediated killing in porcine and rabbit
      sera. In addition, the DeltaopsX and DeltarfaF mutant strains showed impaired
      ability to adhere to and invade porcine kidney epithelial cells (PK-15) and
      porcine umbilical vein endothelial cells, indicating roles for heptose I and II
      residues in the interaction with host cells. The DeltawaaQ mutant strain, with no
      obvious truncation of LOS structure, did not exhibit significant defects in
      adhesion to and invasion of host cells. This study provides insight into the
      contribution of the inner core oligosaccharide, especially heptose I and heptose
      II residues, to the virulence-associated properties of H. parasuis.

PMID- 22857893
TI  - Enteroscopy of the canine gastrointestinal tract: a push to go deeper.

PMID- 22857894
TI  - Inhibition of phosphoinositide-3 kinase pathway down regulates ABCG2 function and
      sensitizes malignant pleural mesothelioma to chemotherapy.
AB  - Malignant pleural mesothelioma (MPM) is a relatively chemoresistant malignancy.
      Diverse biological targets are under investigation to develop new therapeutic
      options. One of these targets, namely the phosphoinositide-3-kinase (PI3K)
      pathway, has been shown to be a regulator of the side population (SP) phenotype
      in different cancers. The SP phenotype is due to drug efflux abilities providing
      drug-resistant properties. The presence of a SP fraction in MPM was recently
      observed in our laboratory. The aim of this study was to investigate the role of
      the PI3K pathway in the regulation of the SP phenotype in MPM. Treatment of
      overnight serum-starved cells with IGF increased phosphorylation of downstream
      target AKT, S6 and 4EBP1 and SP fraction in ZL55, ZL34 and SDM103T2 MPM cell
      lines. The PI3K/mTOR inhibitor NVP-BEZ235 and PI3K inhibitor wortmannin reduced
      the phosphorylation of downstream target AKT, S6 and 4EBP1 and decreased the SP
      fraction. Chemotherapy resistance mediated by drug efflux was tested by treating
      the cells with mitoxantrone. NVP-BEZ235 increased mitoxantrone cytotoxicity and
      this effect was mimicked by fumitremorgin C, a specific ABCG2 inhibitor, although
      not to the same extent, indicating that ABCG2-mediated drug efflux participates
      to chemoresistance. The involvement of ABCG2 in drug efflux was confirmed by
      determination of ABCG2-mediated decrease of intracellular mitoxantrone
      accumulation and silencing experiments. NVP-BEZ235-mediated decrease in drug
      efflux was associated with a significant decrease of ABCG2 present at the cell
      surface in ZL55 and SDM103T2 cells. In conclusion, the PI3K pathway is playing an
      important role in regulating the SP phenotype in MPM cells and inhibition of this
      activity may contribute to a more efficient cancer treatment.

PMID- 22857895
TI  - Evaluating food menus from daycare centers in Guatemala City: descriptive and
      analytical approaches.
AB  - OBJECTIVE: This objective of this study was a methodological analysis of the
      variety and diversity of dietary items and their different origins offered in
      institutional menus across four daycare centers serving low-income families in
      Guatemala City. METHODS: Foods, as served in daycare centers, were used to
      explore and illustrate the different approaches to evaluating food quality. Foods
      served at daycare centers were analyzed for variety (number of different items)
      and diversity (using three food-classification systems). The weight and energy
      contributions for each meal were reported for animal, plant, mixed, or water;
      modern versus traditional foods; fortified versus non-fortified foods; and
      processed versus unprocessed foods. RESULTS: During 5 d of observation, three of
      the four daycare centers served 100% of the food groups of the current Guatemalan
      and international classification systems. In addition, the results showed the
      four daycare centers provided mainly traditional and non-fortified plant-based
      foods. However, although the traditional foods contributed more by weight, the
      modern foods contributed more energy. These findings showed that the "modern"
      foods served at daycare centers are energy dense compared with traditional foods.
      CONCLUSIONS: These daycare centers contributed to variety and diversity while
      serving mainly traditional, plant-based foods. Our analysis went beyond the
      simple existence (mention) of a food as consumed to weight in grams or calories
      to provide potentially new and useful perspectives for understanding how
      guidelines for healthful eating patterns can be promoted and assessed, not only
      in children or in institutions but across all age groups, and settings.

PMID- 22857896
TI  - Age-related increase of stem marker expression influences vascular smooth muscle
      cell properties.
AB  - OBJECTIVE: Aging represents a major risk factor for vascular disease development.
      With aging, changes of the biological properties of vascular smooth muscle cells
      (SMCs) are observed. Stem marker expression characterizes SMCs during
      developmental growth and atherosclerosis, but the contribution of SMCs with stem
      features to the age-related arterial remodeling remains largely unknown. METHODS
      AND RESULTS: Immunostaining revealed rare vascular growth factor receptor-1(+)
      (flt-1(+)) and c-kit(+) cells in tunica media of grossly normal human young (17
      30 years old) large arteries and 2-month old rat aorta, whereas CD133(+) cells
      were absent. In large arteries of human aged donors (64-77 years), flt-1(+) and c
      kit(+) cell number increased in the intimal thickening and tunica media. Double
      immunofluorescence revealed that 30.6 +/- 3% of flt-1(+) intimal cells co
      expressed alpha-smooth muscle actin. Immunostaining, blots and RT-PCR documented
      the increased expression of flt-1 and c-kit in 20-24-month old rat aortic media.
      In vitro, old rat aortic SMCs proliferated and migrated more with greater flt-1,
      c-kit, NF-kappaB, VCAM-1, IAP-1 and MCP-1 levels and less alpha-smooth muscle
      actin and myosin compared to young SMCs. Old SMCs were also more susceptible to
      all-trans retinoic and NF-kappaB inhibition-induced apoptosis compared to young
      SMCs. Anti-flt-1 blocking antibody reduced migration and placental growth factor
      induced but not serum and PDGF-BB-stimulated proliferation of old SMCs.
      CONCLUSIONS: The increase of flt-1(+) and c-kit(+) SMCs characterizes large
      arteries of aged donors; the blocking of flt-1 signaling influences the behavior
      of old SMCs, suggesting that the accumulation of SMCs with a stem phenotype
      contributes to the age-dependent adverse arterial remodeling.

PMID- 22857897
TI  - Accumulation of tissue advanced glycation end products correlated with glucose
      exposure dose and associated with cardiovascular morbidity in patients on
      peritoneal dialysis.
AB  - OBJECTIVES: Accumulation of tissue advanced glycation end products (AGEs) is a
      marker of cumulative glycemic and/or oxidative stress. Cutaneous AGEs levels
      measured by skin autofluorescence correlate well with cardiovascular outcomes in
      diabetes and hemodialysis (HD) patients. The present study aimed to compare
      tissue AGEs levels with peritoneal dialysis (PD) and HD patients and to evaluate
      the relationship between skin autofluorescence and cardiovascular morbidity in
      patients on PD. METHODS: A total of 2388 maintenance dialysis patients (613 PD
      and 1775 HD) were enrolled in this cross-sectional study. Skin autofluorescence
      was measured non-invasively with an autofluorescence reader. Cardiovascular
      morbidity was defined as clinically diagnosed ischemic heart disease, heart
      failure, stroke or peripheral vascular disease from initiation of dialysis.
      RESULTS: More than 90% of patients on both PD and HD had met current dialysis
      adequacy targets. Compared to HD group, PD patients receiving conventional
      glucose-containing dialyzate had significantly higher skin autofluorescence
      values in each category of age and dialysis duration, irrespective of the
      presence or absence of diabetes. In PD patients, skin autofluorescence values
      were strongly correlated with the duration of PD and glucose exposure dose and
      independently associated with cardiovascular morbidity. Multivariate analysis
      revealed that glucose exposure dose and skin autofluorescence were the strongest
      risk factors for cardiovascular morbidity in PD patients after adjustment by age,
      gender, and other classic- or uremic-related risk factors. CONCLUSIONS:
      Accumulation of tissue AGEs provides a potential link between PD exposure of
      metabolic stress and progression of cardiovascular disease in patients on PD.

PMID- 22857898
TI  - Inhibition of neointimal hyperplasia in the rat carotid artery injury model by a
      HMGB1 inhibitor.
AB  - OBJECTIVE: High mobility group box 1 protein (HMGB1) is expressed in
      atherosclerotic lesions. However, its role in vascular system is unknown. In this
      study, we explore whether the inhibition of HMGB1 attenuates neointimal formation
      in animal models. METHODS AND RESULTS: Experiments were performed with VSMCs from
      thoracic aorta of SD rats in vitro, and a rat carotid artery balloon injury model
      in vivo. HMGB1 levels were increased after stimulation of angiotensin II (Ang II)
      and 10% serum in cultured VSMCs. HMGB1 inhibitor (glycyrrhizin) significantly
      inhibited the proliferation and migration of Ang II-treated VSMCs, which was
      accompanied with decreased oxidative stress and inflammation. The underlying
      mechanisms were related with the promotion of antioxidant systems activity and
      deactivation of p38 MAPK/NF-kappaB signaling pathway, respectively. Furthermore,
      inhibition of HMGB1 blunted Notch signaling pathway during VSMCs phenotypic
      transition, and correspondingly restored VSMCs differentiated phenotype under 10%
      serum stimulation. In vivo study, HMGB1 expression was elevated after artery
      injury. Meanwhile, glycyrrhizin treatment suppressed HMGB1 expression, which was
      accompanied with blunted inflammation and oxidative stress after 7 days of
      balloon injury. Moreover, the area of neointimal to media area ratio was
      significantly decreased in glycyrrhizin group compared with injury group at 14
      days after balloon injury. CONCLUSIONS: Inhibition of HMGB1 activity attenuated
      VSMCs activation and neointimal formation after carotid injury. Therefore,
      blockage of HMGB1 might represent a novel therapeutic strategy for vascular
      injury.

PMID- 22857899
TI  - The transfer of stable 133Cs from rice to Japanese sake.
AB  - Possible contamination by radioactive cesium (Cs), released by the Fukushima
      Daiichi Nuclear Plant Accident in Japan on March 2011, has been a matter of
      concern with respect to Japanese sake made from rice grains cultivated in
      affected fields. In this study, the behavior of stable (133)Cs, which is a useful
      analogue for predicting the behavior of radioactive Cs, was investigated in the
      production of sake using rice grains harvested in Japan in 2010. The
      concentration of stable (133)Cs in the polished rice grains decreased gradually
      with decreasing milling ratios until a ratio of 70% was reached, and below that
      point, it did not change significantly. The (133)Cs concentration in the 70%
      polished rice was approximately 20% of that found in brown rice. The sake was
      brewed on a small scale using 70% polished rice, and the transfer of (133)Cs from
      rice to sake was examined. Approximately 30-40% of (133)Cs in the 70% polished
      rice was removed during the washing and the steeping of the rice grains, and
      approximately 40% of the (133)Cs in the 70% polished rice was transferred to the
      sake. If the radioactive Cs species behaves similarly, these results suggest that
      brown rice containing 100 Bq/kg radioactivity of Cs would generate 70% polished
      rice grains containing 20 Bq/kg and that the sake brewed from these grains would
      contain 3-5 Bq/kg.

PMID- 22857900
TI  - AOBP needs to be accurate.

PMID- 22857901
TI  - Coronary artery dissection in Prader-Willi syndrome: case report and literature
      review.
AB  - Prader-Willi syndrome (PWS) is a syndrome characterized in babies by small birth
      weight, hypogonadism, flaccid muscle tone, and skeletal abnormalities, and in
      older children by intense food cravings leading to morbid obesity, hypoxemia, and
      right heart failure. To our knowledge, PWS has not been associated with coronary
      artery dissection. We report a 17-year-old woman with PWS who suffered an
      inferior myocardial infarction secondary to dissection of her right coronary
      artery.

PMID- 22857902
TI  - The thalamus and language revisited.
AB  - Regionalization of language function within the left thalamus has been
      established with language and verbal memory effects of thalamic stimulation
      during surgery for movement disorders. Three distinct language effects of
      thalamic stimulation were established: anomia from posterior ventrolateral (VL)
      and pulvinar regions; perseveration from mid-VL regions; and, a memory and
      acceleratory effect from anterior VL, described as a "specific alerting response"
      (SAR). These studies are reviewed in context of pertinent contemporary and recent
      literature on the thalamic role in memory and language. An explicit mechanistic
      model for the anomia and SAR effect is proposed. The suggested model for the SAR
      effect involves secondary switching in the striatum by the activation of
      thalamostriatal projections, whereas the anomia effect implicates the disruption
      of the cortical synchronization action of pulvinar via the cortico-pulvinar
      cortical projection system. Further experimental data is required to firmly
      establish these mechanisms.

PMID- 22857903
TI  - Mechanical control of integrin-mediated adhesion and signaling.
AB  - Integrin-mediated adhesion is controlled by the number of bonds between cell
      surface integrins and substrate-bound ligands. Integrin-ligand affinity is
      modulated by chemical allostery, mechanical allostery and integrin clustering.
      This review analyzes how each of these factors changes through the phases of cell
      attachment, adhesion strengthening, and clustering. The analysis predicts a
      dominant role of mechanical factors in both adhesive regulation and integrin
      signaling for adherent cells. New approaches and experimental analyses will be
      required to substantiate this hypothesis.

PMID- 22857904
TI  - Acceleration of deposition of Abeta(1-40) peptide on ultrasonically formed
      Abeta(1-42) nucleus studied by wireless quartz-crystal-microbalance biosensor.
AB  - High-frequency (~ 55 MHz) wireless quartz-crystal microbalance biosensor was used
      for studying heterogeneous deposition behavior of Abeta(1-40) peptide on Abeta(1
      42) nuclei, which were grown under the stirring agitation and 200-kHz
      ultrasonication at pH 2.2, 4.6, and 7.4. The deposition reaction was monitored
      over 40 h, and the deposition rate was deduced. Among the agitation nuclei, the
      maximum deposition rate was observed on the nucleus grown at pH 4.6. However,
      ultrasonication nucleus grown at pH 7.4 produced much larger deposition rate,
      despite the same beta-sheet concentration. This result indicates that local
      structural modulation is caused in the nucleus by ultrasonication, which adsorbs
      the Abeta peptide more actively than other nuclei. The resultant deposits clearly
      show oligomeric structure.

PMID- 22857905
TI  - Highly amplified electrochemiluminescence of peroxydisulfate using bienzyme
      functionalized palladium nanoparticles as labels for ultrasensitive immunoassay.
AB  - An immunosensor based on the electrochemiluminescence (ECL) of peroxydisulfate
      was firstly proposed by coupling the cooperation of two enzymes to in situ
      generate coreactant with palladium nanoparticles (PdNPs) as catalyst for the ECL
      reaction. PdNPs were previously synthesized, which successfully attached to
      functional carbon nanotubes (FCNTs), to bind the secondary antibody and bienzyme
      (horseradish peroxidase and glucose oxidase). Then the prepared bioconjugates
      were introduced to the electrode via sandwich immunoreactions. Accordingly, a
      dramatically amplified ECL signal was obtained for that GOD catalyzed glucose to
      produce H(2)O(2) which was subsequently reduced by HRP to in situ generate O(2),
      then PdNPs as catalyst for the ECL reaction of peroxydisulfate/O(2). The present
      immunosensor was used to detect alpha-1-fetoprotein (AFP) and showed a wide
      linear range of 1*10(-5)-100ng mL(-1), with a low detection limit of 3.3fg mL(
      1)(S/N=3). This new signal amplification strategy for preparation of the ECL
      immunosensor could be easily realized and has a potential application in
      ultrasensitive bioassays.

PMID- 22857906
TI  - Direct detection of genomic DNA by surface plasmon resonance imaging: an
      optimized approach.
AB  - The direct detection of specific sequences in genomic DNA samples is very
      challenging in the biosensor-based approach. In this work we developed an
      optimized strategy for the direct detection of DNA sequences in human genomic
      samples by a surface plasmon resonance imaging technology. As model study, the
      target analyte was identified in a DNA sequence mapping the human ABCB1 gene. The
      computed-assisted approach was here applied for probe design. After a preliminary
      evaluation of the probe functioning by the complementary synthetic target, the
      system was applied to the direct detection of the target sequence in human
      genomic DNA extracted from lymphocytes. To achieve this result, several steps
      aimed to improve the analytical performances of the biosensor were studied and
      optimized. The immobilization chemistry, based on thiolated probes, was adapted
      here to non-amplified sequence detection. DNA sample pre-treatments, i.e. genomic
      fragmentation by ultrasounds and dsDNA denaturation by thermal treatment were
      also investigated. A sandwich-like strategy, by using a secondary probe, was also
      applied to understand and confirm the selectivity of the developed biosensor in
      detecting ABCB1 gene in genomic samples. Finally, a reliable calibration curve of
      ABCB1 was obtained with an experimental detection limit of 140 aM. Furthermore,
      the biosensor was well regenerable, assuring up to thirty cycles of effective
      measurements.

PMID- 22857907
TI  - Detection of multi-color fluorescent objects with single photon spectrometer.
AB  - Single photon counting is the most sensitive and accurate method for detection of
      very weak fluorescent signals obtained in many applications such as DNA
      sequencing, detection of biological reporters on micro-beads, detection of
      droplets in micro-fluidic systems, etc. In this paper we describe the use of
      single photon spectrometer for detection and characterization of very weak
      multicolor fluorescence produced by mixtures of various fluorescent dyes and
      quantum dots.

PMID- 22857908
TI  - Relationship between glycated hemoglobin and glucose concentrations in the adult
      Galician population: selection of optimal glycated hemoglobin cut-off points as a
      diagnostic tool of diabetes mellitus.
AB  - AIMS/HYPOTHESIS: To analyze the relationship between glucose and glycated
      hemoglobin (HbA(1c)) in the adult Galician population, evaluate the use of
      HbA(1c) for the screening and diagnosis of diabetes, and calculate the diagnostic
      threshold required for this purpose. METHODS: We analyzed data on 2848 subjects
      (aged 18-85 years) drawn from a study undertaken in 2004 to assess the prevalence
      of diabetes in Galicia. For study purposes, diabetes was defined using the
      criteria recommended in 2002. Participants were classified into four glucose
      based groups. The relationship between glucose and HbA(1c) was described using
      linear regression models, generalized additive models and Spearman's correlation.
      Diagnostic capacity was assessed, and optimal HbA(1c) cut-off points were
      calculated as a diabetes marker using the receiver operating characteristic
      curve. RESULTS: Prevalence of pre-diabetes, unknown diabetes and known diabetes
      was 20.86, 3.37 and 4.39%, respectively. The correlations between HbA(1c) and
      fasting glucose were higher than those obtained for HbA(1c) and glycemia at 2h of
      the oral glucose overload (0.344 and 0.270, respectively). Taking glucose levels
      as the gold standard, a greater discriminatory capacity was obtained for HbA(1c)
      (area under de cruve: 0.839, 95% confidence intervals: 0.788-0.890). Based on the
      study criteria, the optimal minimum and maximum HbA(1c) values were 5.9% and
      6.7%, respectively. CONCLUSIONS/INTERPRETATION: HbA(1c) did not prove superior to
      glycemia for diagnosis of diabetes in the adult Galician population, and cannot
      therefore be used to replace the oral glucose tolerance test for screening and
      diagnosis purposes. Indeed, determination of glucose is essential to verify the
      diagnosis in the majority of cases.

PMID- 22857909
TI  - The effect of search term on the quality and accuracy of online information
      regarding distal radius fractures.
AB  - PURPOSE: Recent emphasis on shared decision making and patient-centered research
      has increased the importance of patient education and health literacy. The
      internet is rapidly growing as a source of self-education for patients. However,
      concern exists over the quality, accuracy, and readability of the information.
      Our objective was to determine whether the quality, accuracy, and readability of
      information online about distal radius fractures vary with the search term.
      METHODS: This was a prospective evaluation of 3 search engines using 3 different
      search terms of varying sophistication ("distal radius fracture," "wrist
      fracture," and "broken wrist"). We evaluated 70 unique Web sites for quality,
      accuracy, and readability. We used comparative statistics to determine whether
      the search term affected the quality, accuracy, and readability of the Web sites
      found. Three orthopedic surgeons independently gauged quality and accuracy of
      information using a set of predetermined scoring criteria. We evaluated the
      readability of the Web site using the Fleisch-Kincaid score for reading grade
      level. RESULTS: There were significant differences in the quality, accuracy, and
      readability of information found, depending on the search term. We found higher
      quality and accuracy resulted from the search term "distal radius fracture,"
      particularly compared with Web sites resulting from the term "broken wrist." The
      reading level was higher than recommended in 65 of the 70 Web sites and was
      significantly higher when searching with "distal radius fracture" than "wrist
      fracture" or "broken wrist." There was no correlation between Web site reading
      level and quality or accuracy. CONCLUSIONS: The readability of information about
      distal radius fractures in most Web sites was higher than the recommended reading
      level for the general public. The quality and accuracy of the information found
      significantly varied with the sophistication of the search term used. CLINICAL
      RELEVANCE: Physicians, professional societies, and search engines should consider
      efforts to improve internet access to high-quality information at an
      understandable level.

PMID- 22857910
TI  - A biomechanical comparison of 3 loop suture materials in a 6-strand flexor tendon
      repair technique.
AB  - PURPOSE: The braided polyblend (FiberWire) suture is recognized for its
      superiority in tensile strength in flexor tendon repair. The purpose of this
      study was to compare the biomechanical performance of 3 loop-suture materials
      used in a locking 6-strand flexor tendon repair configuration: braided polyblend
      (FiberLoop 4-0), cable nylon (Supramid Extra II 4-0), and braided polyester
      (Tendo-Loop 4-0). We hypothesized that, using this technique, the braided
      polyblend suture would give superior tensile strength compared with the other 2
      suture materials. METHODS: We divided 30 fresh porcine flexor tendons
      transversely and repaired each with 1 of the 3 suture materials using a modified
      Lim-Tsai 6-strand suture technique. We loaded the repaired tendons to failure
      using a materials testing machine and collected data on the mechanism of failure,
      ultimate tensile strength, gap strength, and stiffness. RESULTS: Failure
      mechanisms for the repaired specimens were as follows: the braided polyblend had
      50% suture breakage and 50% suture pullout; the cable nylon had 100% suture
      breakage; and the braided polyester had 80% suture breakage and 20% suture
      pullout. Specimens repaired with the braided polyblend suture had the highest
      mean ultimate tensile strength (97 N; standard deviation, 22) and the highest
      mean gap force (35 N; standard deviation, 7). CONCLUSIONS: This study supports
      the findings of previous studies showing superior strength of the braided
      polyblend suture. CLINICAL RELEVANCE: We were able to achieve up to 124 N in
      ultimate tensile strength and 48 N of gap force with this suture in porcine
      tendons. This gives greater confidence in starting immediate controlled passive
      or active rehabilitation after repair of flexor tendon injuries.

PMID- 22857911
TI  - Percutaneous pinning of middle phalangeal neck fractures: surgical technique.
AB  - Extra-articular middle phalangeal neck fractures are uncommon fractures of the
      hand that are often difficult to treat. Surgery is indicated when closed
      reduction fails; 1 option is closed reduction and percutaneous pinning.
      Maintaining closed reduction while inserting K-wires is challenging. We present a
      new technique for percutaneous pinning of these fractures that was developed to
      address these issues. Our technique uses flexion of the interphalangeal joints
      during K-wire insertion to maintain fracture reduction and improve fixation.

PMID- 22857912
TI  - Surgical correction of the "Popeye biceps" deformity: dual-window approach for
      combined subpectoral and deltopectoral access and proximal biceps tenodesis.
AB  - "Popeye biceps" deformity represents the appearance of a distally retracted
      biceps muscle resulting from either a traumatic long biceps tendon (LBT) rupture
      or an iatrogenic LBT tenotomy. Cosmetic and functional problems associated with
      the deformity may necessitate surgical correction, and surgical exposure using
      multiple incisions is recommended. The technique presented here describes a novel
      mini-open approach using a single 1-in incision that provides access to 3
      peripectoral anatomical zones. Preoperative sonographic localization of the
      ruptured and retracted LBT is used to guide incision placement, and facilitates
      intraoperative tendon retrieval via a limited incision and minimal dissection.
      Inferolateral retraction of the mini-incision window permits infrapectoral and
      subpectoral LBT mobilization and dissection. Deltopectoral access via
      superomedial retraction of the same skin window is used to expose the
      suprapectoral zone and is employed for LBT retrieval and proximal tenodesis.
      Technical tips for safe dissection via a mini-incision, and methods for
      biological LBT augmentation are discussed.

PMID- 22857913
TI  - Relationship duration moderation of identity status differences in emerging
      adults' same-sex friendship intimacy.
AB  - Previous research has not yielded consistent identity and intimacy associations
      for female and male emerging adults. Intimacy varies with time spent in a
      relationship, and relationship duration may explain variations in the identity
      process association with intimacy. Data from 278 female and 156 male emerging
      adults revealed relationship duration moderated the identity commitment and
      exploration associations with intimacy. Findings indicated longer relationship
      duration was associated with lower intimacy levels for high identity
      commitment/high exploration females, and longer relationship duration was
      associated with higher intimacy levels for high commitment/low exploration
      females. Findings also indicated longer relationship duration was associated with
      higher intimacy levels for high commitment/high exploration males, and longer
      relationship duration was associated with lower intimacy levels for low
      commitment/high exploration males. Findings are discussed with regards to the
      empirical importance of considering relationship characteristics when examining
      emerging adult identity process associations with friendship intimacy.

PMID- 22857914
TI  - Indoor air quality in Montreal area day-care centres, Canada.
AB  - Indoor air quality (IAQ) has been understudied in day-care centres (DCCs), even
      though it can affect the respiratory health of children. This study was
      undertaken to assess IAQ in a randomly selected sample of 21 DCCs having space
      for at least 40 children in Montreal, Canada, and to determine associations
      between building characteristics and IAQ. Questionnaires on building
      characteristics and operation of the DCC were administered to managers.
      Temperature, relative humidity, and concentrations of carbon dioxide (CO(2)),
      formaldehyde and volatile organic compounds were measured in January and February
      2008 in rooms attended by children aged between 18 and 60 months. Most DCCs (81%)
      had a mechanical ventilation system. Over 85% of the DCCs had a mean CO(2)
      concentration higher than 1000 ppm, the value generally targeted for comfort in
      buildings. Mean CO(2) concentrations were significantly lower in DCCs having a
      floor space meeting the provincial standards. The mean (standard deviation-SD)
      formaldehyde concentration was 22.9 (8.2) MUg/m(3), with all participating DCCs
      being within Health Canada's Residential IAQ Guideline of 50 MUg/m(3). The
      presence of a mechanical ventilation system and a large surface of play area per
      child were significantly associated with lower CO(2) levels, explaining 44% of
      the variance in indoor CO(2) concentrations. The presence of a mechanical
      ventilation system was also associated with significantly lower formaldehyde and
      acetaldehyde levels. Moreover, 68% of the variance in indoor acetaldehyde
      concentrations was explained by CO(2) levels, indicating that CO(2) was a better
      proxy of ventilation than the presence of a ventilation system, as this latter
      variable did not imply that the ventilation system was running or functioning
      adequately. These results demonstrate the need for on-going efforts to ensure
      sufficient floor space and adequate ventilation in DCCs to maintain good IAQ.

PMID- 22857915
TI  - Isolated pulmonary valve endocarditis in a normal heart.
AB  - Isolated pulmonary valve endocarditis is a very rare entity, usually associated
      with intravenous drug abuse. We describe a case of isolated pulmonary valve
      endocarditis in a diabetic patient with no apparent precipitating factors besides
      a lesion on the right hallux. The clinical course was favorable and he was
      discharged home after a six-week course of antibiotic therapy.

PMID- 22857916
TI  - Three-tier versus five-tier fetal heart rate classification systems.

PMID- 22857917
TI  - Naked caspase 3 small interfering RNA is effective in cold preservation but not
      in autotransplantation of porcine kidneys.
AB  - BACKGROUND: Caspase 3 associated with apoptosis and inflammation plays a key role
      in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering
      RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not
      in autotransplantation. MATERIALS AND METHODS: The left kidney was retrieved from
      mini pigs and infused with the University of Wisconsin solution with or without
      0.3mg of caspase 3 siRNA into the renal artery with the renal artery and vein
      clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was
      autotransplanted into the right for 48 h without systemic treatment of siRNA.
      RESULTS: Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS
      kidneys but was weakened after transplantation. The expression of caspase 3
      messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In
      the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA
      and active subunit were upregulated with further decreased precursor but
      increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells.
      Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal
      function was not significantly changed. CONCLUSIONS: Naked caspase 3 siRNA
      administered into the kidney was effective in cold preservation but not enough to
      protect posttransplant kidneys, which might be because of systemic complementary
      responses overcoming local effects.

PMID- 22857918
TI  - The role of exogenous adenosine triphosphate administration for the prevention of
      ischemia-reperfusion injury in skeletal muscle.

PMID- 22857919
TI  - Incomplete thermal ablation of hepatocellular carcinoma: effects on tumor
      proliferation.
AB  - INTRODUCTION: Local recurrence after thermal ablation of hepatocellular carcinoma
      (HCC) is common, problematic, and poorly understood. The continued effects of the
      heat sink around major vessels have been hypothesized to increase local ablation
      failure and possibly enhance the growth of the incompletely ablated malignancy.
      The aim of this study was to evaluate the critical temperature to which
      incomplete ablation would occur. METHODS: Established murine (Hep-6L), rodent
      (Hep-4IIE), and human (Hep-G2) HCC cells were cultivated and then exposed to
      variable 2 degrees  temperatures from 37  degrees C-54  degrees C and incubated
      at 37  degrees C for 72 h. After incubation, 3-(4, 5-dimthyl-thiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL) assays were used to measure
      proliferation, metabolic activity, and apoptosis. RESULTS: Reliable cell death
      occurred in all three cell lines by microscopy and MTT assay after treatment at
      temperatures above 48  degrees C. However, in the 72 h after treatment, we
      observed successive recovery or maintenance of cellular proliferation at each
      time endpoint at <=47  degrees C. This effect was present across all cell lines
      at 45  degrees C, and was most pronounced in the Hep-6L and Hep-4IIE cell lines
      (P < 0.05). Hep-G2 cells demonstrated maintenance of proliferation by MTT assay
      over the 72 h following treatment at 45  degrees C. TUNEL assays were strongly
      positive at temperatures >=48  degrees C. TUNEL positivity suggests death via
      apoptotic mechanisms as opposed to coagulative processes seen at higher
      temperatures. Cells treated at these higher temperatures had a statistically
      significant (P < 0.05) higher apoptotic index as measured by TUNEL positivity,
      despite being morphologically similar by light microscopy. CONCLUSIONS: Cellular
      proliferation and resistance to apoptosis are significantly increased after
      incomplete thermal ablation, with a 2 degrees  difference in complete versus
      incomplete ablation.

PMID- 22857920
TI  - Imaging fluorescently labeled complexes by means of multidimensional correlative
      light and transmission electron microscopy: practical considerations.
AB  - These days the common ground between structural biology and molecular biology
      continues to grow thanks to the biomolecular insights offered by correlative
      microscopy, even though the vision of combining insights from different imaging
      tools has been around for nearly four decades. The use of correlative imaging
      methods to dissect the cell's internal structure is progressing faster than ever
      as shown by the boom in the number of methodological approaches available for
      correlative microscopy studies, each designed to address a specific scientific
      question. In this chapter, we will present a relatively straightforward approach
      to combining information from fluorescence microscopy and electron microscopy at
      the supramolecular level. The method combines live-cell and/or confocal laser
      microscopy with classical sample preparation for transmission electron microscopy
      (TEM), thereby allowing the integration of dynamic details of subcellular
      processes with insights about the organelles and molecular machinery involved. We
      illustrate the applicability of this multidimensional correlative microscopy
      approach on cultured Caco-2 colorectal cancer cells exposed to fluorescently
      labeled cisplatin, and discuss how these methods can deepen our understanding of
      key cellular processes, such as drug uptake and cell fate.

PMID- 22857921
TI  - Visualizing live dynamics and ultrastructure of intracellular organelles with
      preembedding correlative light-electron microscopy.
AB  - One of the very effective methods to perform correlative light-electron
      microscopy (CLEM) is to combine video imaging of live cells with immuno-electron
      microscopy. This technique can thus provide detailed, high-resolution
      characterization of dynamic intracellular organelles. The use of green
      fluorescent protein (GFP)-tagged chimeras allows the movements and/or behavior of
      intracellular structures in a live cell to be followed, which can then be fixed
      at the moment of interest. The subsequent immuno-electron microscopy analysis
      reveals the three-dimensional (3D) architecture of the same structure, together
      with the precise identification of the GFP-labeled protein pattern. The process
      resembles taking a high-resolution snapshot of an interesting and/or rare live
      event. Conceptually, it consists of a switch of wavelengths, from that of photons
      to that of electrons, with the associated huge gain in resolution. In this
      respect, CLEM can be considered as the first, and probably one of the most
      powerful, super-resolution microscopy techniques. This switch, however, requires
      complex manipulations of the sample. Considering that CLEM is a very valuable but
      technically challenging and time-consuming method, accurate protocols are needed
      to simplify the efforts of researchers who are willing to apply this method for
      their own purposes. Here, we present a detailed description of the preembedding
      CLEM procedures that explains the know-how and the "tricks of the trade" that are
      involved in carrying out the crucial steps of CLEM.

PMID- 22857922
TI  - Correlative fluorescence and transmission electron microscopy in tissues.
AB  - Correlative microscopy has meant different things over the years; currently, this
      term refers to imaging the same exact structures with two or more imaging
      modalities. This commonly involves combining fluorescence and electron
      microscopy. Much of the recent work related to correlative microscopy has been
      done using cell culture models. However, many biological questions cannot be
      addressed in these models, but require instead the 3-dimensional organization of
      cells found in tissues. Herein, we discuss some of the issues related to
      correlative microscopy of tissues including the major reporter systems presently
      available for correlative microscopy. We present data from our own work in which
      we have focused on the use of ultrathin cryosections of tissues as the substrate
      for immunolabeling to combine immunofluorescence and electron microscopy of the
      same sub-cellular structures.

PMID- 22857923
TI  - Correlative light and electron microscopy in parasite research.
AB  - The interaction of a parasite and a host cell is a complex process, which
      involves several steps: (1) attachment to the plasma membrane, (2) entry inside
      the host cell, and (3) hijacking of the metabolism of the host. In biochemical
      experiments, only an event averaged over the whole cell population can be
      analyzed. The power of microscopy, however, is to investigate individual events
      in individual cells. Therefore, parasitologists frequently perform experiments
      with fluorescence microscopy using different dyes to label structures of the
      parasite or the host cell. Though the resolution of light microscopy has greatly
      improved, it is not sufficient to reveal interactions at the ultrastructural
      level. Furthermore, only specifically labeled structures can be seen and related
      to each other. Here, we want to demonstrate the additional value of electron
      microscopy in this area of research. Investigation of the different steps of
      parasite-host cell interaction by electron microscopy, however, is often hampered
      by the fact that there are only a few cells infected, and therefore it is
      difficult to find enough cells to study. A solution is to profit from low
      magnification, hence large overview, and specific location of the players by
      fluorescence labels in a light microscope with the high power resolution and
      structural information provided by an electron microscope, in short by
      correlative light and electron microscopy.

PMID- 22857924
TI  - Labeling of ultrathin resin sections for correlative light and electron
      microscopy.
AB  - Correlative microscopy combines the versatility of the light microscope with the
      excellent spatial resolution of the electron microscope. Here, we describe fast
      and simple methods for correlative immunofluorescence and immunogold labeling on
      the very same ultrathin section. The protocols are demonstrated on sections of
      tissue samples embedded in the methacrylate Lowicryl K4M. Ultrathin sections are
      mounted on electron microscopy (EM) grids and stained simultaneously with
      fluorescent and gold markers. For the detection of primary antibodies, we applied
      either protein A gold or immunoglobulin G (IgG) gold in combination with
      secondary antibodies coupled to Alexa488 or Alexa555. Alternatively, the
      correlative marker FluoroNanogold was used, followed by silver enhancement. The
      samples have to be analyzed first at the light microscope and then in the
      transmission electron microscope (TEM), because the fluorescence is bleached by
      the electron beam. Labeled structures selected at the fluorescence microscope can
      be identified in the TEM and analyzed at high resolution. This way, fluorescent
      signals can be directly correlated to the corresponding subcellular structures in
      the area of interest.

PMID- 22857925
TI  - 3D HDO-CLEM: cellular compartment analysis by correlative light-electron
      microscopy on cryosection.
AB  - Fundamental to obtaining a depth-understanding of the function and structure of
      cells is the ability to study and correlate their molecular topography with the
      ultrastructural morphology, for example, to visualize the position of a given
      protein relative to a given cell compartment and its morphology. Standard
      fluorescence light microscopy (FLM) relies on simple sample preparations, and
      localizes proteins in living or fixed cells with a resolution in the range of few
      hundred nanometers, allowing large field of view. However, FLM is unable to
      visualize the unlabeled cellular context. On the other hand, electron microscopy
      (EM) techniques reveal protein topology with the resolution in a range of a few
      tens of nanometer, retains the cellular context, but can only be applied on a
      limited field of view. Therefore, both approaches present shortcomings, in terms
      of field of view, statistical output, resolution, sample preparation, and context
      analysis, that can likely complement each other. To bridge the gap between FLM
      imaging and EM, several laboratories have developed methods for correlative light
      electron microscopy (CLEM). In a nutshell, CLEM enables one to investigate the
      same exact region of interest utilizing the two microscope platforms, and thereby
      virtually combine their capabilities. In this chapter, we describe a protocol
      based on immunolabeling of Tokuyasu cryosections that allows correlation of LM
      and EM images with excellent preservation of cellular ultrastructure. We will
      refer to this method as high-data-output CLEM (HDO-CLEM). The major benefits of
      HDO-CLEM are the possibility to (1) correlate several hundreds of events at the
      same time, (2) perform three-dimensional (3D) correlation, (3) immunolabel both
      endogenous and recombinantly tagged proteins at the same time, and (4) combine
      the high data analysis capability of FLM with the high precision of transmission
      EM in a CLEM hybrid morphometric analysis. We have identified and optimized
      critical steps in sample preparation, defined routines for sample analysis and
      retracing of regions of interest, developed software for semi/fully automatic 3D
      FLM reconstruction and set the basis for a hybrid light/EM morphometry approach.

PMID- 22857926
TI  - Correlative light and electron microscopy of GFP.
AB  - The correlation of light and electron microscopy (EM) is a powerful tool as it
      combines the investigation of dynamic processes in vivo with the resolution power
      of the electron microscope. The green fluorescent proteins (GFPs) and its
      derivatives revolutionized live-cell light microscopy. Hence, this review
      outlines correlative microscopy of GFP through photo-oxidation, a method that
      allows for the direct ultrastructural visualization of fluorophores upon
      illumination. Oxygen radicals generated during the GFP bleaching process photo
      oxidize diaminobenzidine (DAB) into an electron dense precipitate that can be
      visualized both by routine EM of thin sections and by electron tomography for 3D
      analysis. There are different levels of correlative microscopy, i.e. the
      correlation of certain areas, cells, or organelles from light to EM, where photo
      oxidation of DAB through GFP allows the highest possible degree--the correlation
      of specific molecules.

PMID- 22857928
TI  - Correlated light microscopy and electron microscopy.
AB  - Understanding where, when, and how biomolecules (inter)act is crucial to uncover
      fundamental mechanisms in cell biology. Recent developments in fluorescence light
      microscopy (FLM) allow protein imaging in living cells and at the near molecular
      level. However, fluorescence microscopy only reveals selected biomolecules or
      organelles but not the (ultra)structural context, as can be examined by electron
      microscopy (EM). LM and EM of the same cells, so-called correlative (or
      correlated) light and electron microscopy (CLEM), allow examining rare or dynamic
      events first by LM, and subsequently by EM. Here, we review progress in CLEM,
      with focus on matching the areas between different microscopic modalities.
      Moreover, we introduce a method that includes a virtual overlay and automated
      large-scale imaging, allowing to switch between most microscopes. Ongoing
      developments will revolutionize and standardize CLEM in the near future, which
      thus holds great promise to become a routine technique in cell biology.

PMID- 22857929
TI  - Capturing endocytic segregation events with HPF-CLEM.
AB  - We have advocated the use of high-pressure freezing (HPF) in specific types of
      Correlative Light Electron Microscopy (CLEM) experiments because the
      intracellular components such as the cytoskeleton and membrane tubules can only
      be adequately preserved via cryofixation. To allow fast transfer from the light
      microscope into a cryofixation device, we have developed the Rapid Transfer
      System (RTS) for the EMPACT2 high-pressure freezer. In this chapter, we will
      describe how to prepare and perform a CLEM experiment using this device and will
      highlight the latest changes made to the original system to optimize the
      workflow.

PMID- 22857927
TI  - Picking faces out of a crowd: genetic labels for identification of proteins in
      correlated light and electron microscopy imaging.
AB  - Correlated light and electron microscopic (CLEM) imaging is a powerful method for
      dissecting cell and tissue function at high resolution. Each imaging mode
      provides unique information, and the combination of the two can contribute to a
      better understanding of the spatiotemporal patterns of protein expression,
      trafficking, and function. Critical to these methods is the use of genetically
      appended tags that highlight specific proteins of interest in order to be able to
      pick them out of their complex cellular environment. Here we review and discuss
      the current generation of genetic labels for direct protein identification by
      CLEM, addressing their relative strengths and weaknesses and in what experiments
      they would be most useful.

PMID- 22857930
TI  - Targeted ultramicrotomy: a valuable tool for correlated light and electron
      microscopy of small model organisms.
AB  - Correlative light and electron microscopy (CLEM) is used when one needs to
      combine both imaging modalities on the same sample. When working on living small
      model organisms, such as Caenorhabditis elegans, specific CLEM protocols are
      required to acquire high-resolution light microscopic images of a region of
      interest and thereafter to relocate and study the same object at the
      ultrastructural level using a transmission electron microscope. In this chapter,
      we describe how to process living specimens from the confocal microscope to the
      transmission electron microscopy (TEM), focusing on an improved ultramicrotomy
      technique that allows a precise and reliable targeting of the object of interest.
      This improvement significantly reduces the time consuming and frequently
      frustrating search for the region of interest. Our targeted ultramicrotomy
      protocol is versatile enough to be applied on a variety of bulk specimens, such
      as fly and fish embryos, or mouse tissues.

PMID- 22857931
TI  - Correlative light and electron microscopy of intermediate stages of meiotic
      spindle assembly in the early Caenorhabditis elegans embryo.
AB  - This chapter is an update of the previously published book chapter "Correlative
      Light and Electron Microscopy of Early C. elegans Embryos in Mitosis" (Muller
      Reichert, Srayko, Hyman, O'Toole, & McDonald, 2007). Here, we have adapted and
      improved the protocol for the isolated meiotic embryos, which was necessary to
      meet the specific challenges a researcher faces while investigating the
      development of very early Caenorhabditis elegans embryos ex-utero. Due to the
      incompleteness of the eggshell assembly, the meiotic embryo is very fragile and
      much more susceptible to changes in the environmental conditions than the mitotic
      ones. To avoid phototoxicity associated with wide-field UV illumination, we stage
      the meiotic embryos primarily using transmitted visible light. Throughout the
      staging and high-pressure freezing, we incubate samples in an isotonic embryo
      buffer. The ex-utero approach allows precise tracking of the developmental events
      in isolated meiotic embryos, thus facilitating the comparison of structural
      features between wild-type and mutant or RNAi-treated samples.

PMID- 22857932
TI  - Precise, correlated fluorescence microscopy and electron tomography of lowicryl
      sections using fluorescent fiducial markers.
AB  - The application of fluorescence and electron microscopy to the same specimen
      allows the study of dynamic and rare cellular events at ultrastructural detail.
      Here, we present a correlative microscopy approach, which combines high accuracy
      of correlation, high sensitivity for detecting faint fluorescent signals, as well
      as robustness and reproducibility to permit large dataset collections. We provide
      a step-by-step protocol that allows direct mapping of fluorescent protein signals
      into electron tomograms. A localization precision of <100 nm is achieved by using
      fluorescent fiducial markers which are visible both in fluorescence images and in
      electron tomograms. We explain the critical details of the procedure, give
      background information on the individual steps, present results from test
      experiments carried out during establishment of the method, as well as
      information about possible modifications to the protocol, such as its application
      to 2D electron micrographs. This simple, robust, and flexible method can be
      applied to a large variety of cellular systems, such as yeast cell pellets and
      mammalian cell monolayers, to answer a broad spectrum of structure-function
      related questions.

PMID- 22857933
TI  - Integrative approaches for cellular cryo-electron tomography: correlative imaging
      and focused ion beam micromachining.
AB  - The application of cryo-electron tomography to cells and tissues is commonly
      referred to as "cellular tomography," and enables visualization of the
      supramolecular architecture of cells in a near-native state. However, in order to
      access structural features hidden deep inside cellular volumes, it is necessary
      to use hybrid techniques to identify and localize features of interest and
      prepare such regions for subsequent analysis by transmission electron microscopy.
      We present a workflow that integrates different approaches: (1) correlative cryo
      fluorescence microscopy to localize features within frozen-hydrated cells, (2)
      focused ion beam milling to thin these specimens in a targeted manner, and (3)
      cryo-electron tomography to provide detailed information about the cellular
      ultrastructure of thinned samples. We describe the combined use of these
      techniques and the instrumentation required to enable cryo-electron tomography
      for a vast range of cellular samples.

PMID- 22857935
TI  - Atmospheric scanning electron microscope for correlative microscopy.
AB  - The JEOL ClairScope is the first truly correlative scanning electron and optical
      microscope. An inverted scanning electron microscope (SEM) column allows electron
      images of wet samples to be obtained in ambient conditions in a biological
      culture dish, via a silicon nitride film window in the base. A standard inverted
      optical microscope positioned above the dish holder can be used to take reflected
      light and epifluorescence images of the same sample, under atmospheric conditions
      that permit biochemical modifications. For SEM, the open dish allows successive
      staining operations to be performed without moving the holder. The standard
      optical color camera used for fluorescence imaging can be exchanged for a high
      sensitivity monochrome camera to detect low-intensity fluorescence signals, and
      also cathodoluminescence emission from nanophosphor particles. If these particles
      are applied to the sample at a suitable density, they can greatly assist the task
      of perfecting the correlation between the optical and electron images.

PMID- 22857936
TI  - Bridging microscopes: 3D correlative light and scanning electron microscopy of
      complex biological structures.
AB  - The rationale of correlative light and electron microscopy (CLEM) is to collect
      data on different information levels--ideally from an identical area on the same
      sample--with the aim of combining datasets at different levels of resolution to
      achieve a more holistic view of the hierarchical structural organization of cells
      and tissues. Modern three-dimensional (3D) imaging techniques in light and
      electron microscopy opened up new possibilities to expand morphological studies
      into the third dimension at the nanometer scale and over various volume
      dimensions. Here, we present two alternative approaches to correlate 3D light
      microscopy (LM) data with scanning electron microscopy (SEM) volume data. An
      adapted sample preparation method based on high-pressure freezing for structure
      preservation, followed by freeze-substitution for multimodal en-bloc imaging or
      serial-section imaging is described. The advantages and potential applications
      are exemplarily shown on various biological samples, such as cells, individual
      organisms, human tissue, as well as plant tissue. The two CLEM approaches
      presented here are per se not mutually exclusive, but have their distinct
      advantages. Confocal laser scanning microscopy (CLSM) and focused ion beam-SEM
      (FIB-SEM) is most suitable for targeted 3D correlation of small volumes, whereas
      serial-section LM and SEM imaging has its strength in large-area or -volume
      screening and correlation. The second method can be combined with
      immunocytochemical methods. Both methods, however, have the potential to extract
      statistically relevant data of structural details for systems biology.

PMID- 22857934
TI  - Visualizing proteins in electron micrographs at nanometer resolution.
AB  - To understand protein function, we need a detailed description of the molecular
      topography of the cell. The subcellular localization of proteins can be revealed
      using genetically encoded fluorescent proteins or immunofluorescence. However,
      the precise localization of proteins cannot be resolved due to the diffraction
      limit of light. Recently, the diffraction barrier has been overcome by employing
      several microscopy techniques. Using super-resolution fluorescence microscopy,
      one can pinpoint the location of proteins at a resolution of 20 nm or even less.
      However, the cellular context is often absent in these images. Recently, we
      developed a method for visualizing the subcellular structures in super-resolution
      images. Here we describe the method with two technical improvements. First, we
      optimize the method to preserve more fluorescence without compromising the
      morphology. Second, we implement ground-state depletion and single-molecule
      return (GSDIM) imaging, which does not rely on photoactivatable fluorescent
      proteins. These improvements extend the utility of nano-resolution fluorescence
      electron microscopy (nano-fEM).

PMID- 22857937
TI  - Correlative light and volume electron microscopy: using focused ion beam scanning
      electron microscopy to image transient events in model organisms.
AB  - The study of a biological event within a live model organism has become routine
      through the use of fluorescent labeling of specific proteins in conjunction with
      laser confocal imaging. These methods allow 3D visualization of temporal events
      that can elucidate biological function but cannot resolve the tissue
      organization, extracellular and subcellular details of the tissues. Here, we
      present a method for correlating electron microscopy image data with the light
      microscopy data from the same sample volume to reveal the 3D structural
      information: "correlative light and volume electron microscopy." The methods for
      live video confocal microscopy, fixation and embedding of the tissue for electron
      microscopy, the focused ion beam scanning electron microscopy method for
      sequentially slicing and imaging the volume of interest, and the treatment of the
      resulting 3D dataset are presented. The method is illustrated with data collected
      during the angiogenesis of blood vessels in a transgenic zebrafish embryo.

PMID- 22857938
TI  - Introduction to correlative light and electron microscopy.

PMID- 22857939
TI  - Cost effective waste management through composting in Africa.
AB  - Greenhouse gas (GHG) emissions per person from urban waste management activities
      are greater in sub-Saharan African countries than in other developing countries,
      and are increasing as the population becomes more urbanised. Waste from urban
      areas across Africa is essentially dumped on the ground and there is little
      control over the resulting gas emissions. The clean development mechanism (CDM),
      from the 1997 Kyoto Protocol has been the vehicle to initiate projects to control
      GHG emissions in Africa. However, very few of these projects have been
      implemented and properly registered. A much more efficient and cost effective way
      to control GHG emissions from waste is to stabilise the waste via composting and
      to use the composted material as a soil improver/organic fertiliser or as a
      component of growing media. Compost can be produced by open windrow or in-vessel
      composting plants. This paper shows that passively aerated open windrows
      constitute an appropriate low-cost option for African countries. However, to
      provide an usable compost material it is recommended that waste is processed
      through a materials recovery facility (MRF) before being composted. The paper
      demonstrates that material and biological treatment (MBT) are viable in Africa
      where they are funded, e.g. CDM. However, they are unlikely to be instigated
      unless there is a replacement to the Kyoto Protocol, which ceases for
      Registration in December 2012.

PMID- 22857940
TI  - Functional comparison of Deinococcus radiodurans Dps proteins suggests distinct
      in vivo roles.
AB  - Deinococcus radiodurans exhibits extreme resistance to DNA damage and is one of
      only few bacteria that encode two Dps (DNA protection during starvation)
      proteins. Dps-1 was shown previously to bind DNA with high affinity and to
      localize to the D. radiodurans nucleoid. A unique feature of Dps-2 is its
      predicted signal peptide. In the present paper, we report that Dps-2 assembly
      into a dodecamer requires the C-terminal extension and, whereas Dps-2 binds DNA
      with low affinity, it protects against degradation by reactive oxygen species.
      Consistent with a role for Dps-2 in oxidative stress responses, the Dps-2
      promoter is up-regulated by oxidative stress, whereas the Dps-1 promoter is not.
      Although DAPI (4',6-diamidino-2-phenylindole) staining of Escherichia coli
      nucleoids shows that Dps-1 can compact genomic DNA, such nucleoid condensation is
      absent from cells expressing Dps-2. A fusion of EGFP (enhanced green fluorescent
      protein) to the Dps-2 signal peptide results in green fluorescence at the
      perimeter of D. radiodurans cells. The differential response of the Dps-1 and Dps
      2 promoters to oxidative stress, the distinct cellular localization of the
      proteins and the differential ability of Dps-1 and Dps-2 to attenuate hydroxyl
      radical production suggest distinct functional roles; whereas Dps-1 may function
      in DNA metabolism, Dps-2 may protect against exogenously derived reactive oxygen
      species.

PMID- 22857941
TI  - Technologies for global health.

PMID- 22857942
TI  - [A case of Alice-in-Wonderland syndrome probably associated with the use of
      montelukast].

PMID- 22857943
TI  - [Diabetes mellitus: clinical presentation and differential diagnosis of
      hyperglycemia in childhood and adolescence].
AB  - Diabetes mellitus is one of the most common chronic diseases in childhood.
      Despite being a clinical and etiopathogenically heterogeneous disorder, type 1
      autoimmune diabetes accounts for more than 95% of cases in children. Recent
      advances have meant that a growing number of patients have been assigned to other
      subtypes of diabetes. In such cases, the correct diagnosis is facilitated by the
      fact that many of these rare causes of diabetes are associated with specific
      clinical syndromes or may present at a certain age. Many of them are also
      subsidiaries of molecular diagnosis. The aim of this review is to update the
      current knowledge in this field of pediatric diabetes, in an attempt to determine
      the most accurate diagnosis and its implications on appropriate treatment and
      prognosis.

PMID- 22857944
TI  - Cognitive demand and predictive adaptational responses in dynamic stability
      control.
AB  - We studied the effects of a concurrent cognitive task on predictive motor
      control, a feedforward mechanism of dynamic stability control, during disturbed
      gait in young and old adults. Thirty-two young and 27 elderly male healthy
      subjects participated and were randomly assigned to either control or dual task
      groups. By means of a covered exchangeable element the surface condition on a
      gangway could be altered to induce gait perturbations. The experimental protocol
      included a baseline on hard surface and an adaptation phase with twelve trials on
      soft surface. After the first, sixth and last soft surface trial, the surface
      condition was changed to hard (H1-3), to examine after-effects and, thus, to
      quantify predictive motor control. Dynamic stability was assessed using the
      'margin of stability (MoS)' as a criterion for the stability state of the human
      body (extrapolated center of mass concept). In H1-3 the young participants
      significantly increased the MoS at touchdown of the disturbed leg compared to
      baseline. The magnitude and the rate of these after-effects were unaffected by
      the dual task condition. The old participants presented a trend to after-effects
      (i.e., increase of MoS) in H3 but only under the dual task condition.In
      conclusion, the additional cognitive demand did not compromise predictive motor
      control during disturbed walking in the young and old participants. In contrast
      to the control group, the old dual task group featured a trend to predictive
      motor adjustments, which may be a result of a higher state of attention or
      arousal due to the dual task paradigm.

PMID- 22857945
TI  - Flow oscillation - a measure to predict the surgery outcome for obstructed sleep
      apnea (OSA) subject.
AB  - Obstructed sleep apnea (OSA) is a common disorder which may need surgery to widen
      the airway; however the success rate of surgery is limited. Here we report a
      finding that could be used to predict the outcome of the OSA surgery. We found
      that inspiratory flow oscillates due to flow separation near the larynx, and the
      resulting periodic signal (3-5Hz) is an intrinsic property of breathing. This
      flow oscillating signal may be the afferent stimulus to trigger respiratory
      events. It is found that the flow oscillation is attenuated for the OSA subjects.
      The computational fluid dynamics (CFD) simulation reveals that there exists flow
      separation near larynx and this separation is severely weakened in the OSA upper
      airway model. It is believed that the flow oscillating signal can serve as the
      measure to quantify the breathing quality of an OSA subject. This makes it
      possible to predict the surgery outcome of the OSA subject by applying CFD
      simulation.

PMID- 22857946
TI  - Computed tomography, histological and ultrasonic measurements of adolescent
      scoliotic rib hump geometrical and material properties.
AB  - In Adolescent Idiopathic Scoliosis (AIS), numerical models can enhance
      orthopaedic or surgical treatments and provide reliable insights into the
      mechanism of progression. Computational methods require knowledge of relevant
      parameters, such as the specific geometrical or material properties of the AIS
      rib, about which there is currently a lack of information. The aim of our study
      was to determine the geometrical and material properties (Young's modulus [E] and
      Poisson's ratio [nu]) for AIS rib bones. Twelve ribs extracted during gibbectomy
      on 15 and 17 year old girls were tested using computed tomography (CT) scanner,
      histology and ultrasonic scanner. The mean porosity (+/- standard deviation (SD))
      is 1.35 (+/-0.52)% and the mean (+/-SD) bone mineral density is 2188 (+/
      19)mmHA/cc. The cortical part of the AIS rib hump is found to be thicker than
      physiological values in the literature. To mimic the rib hump for an AIS girl,
      our results suggest that ribs should be modeled as hollow circular cylinders with
      a 10.40 (+/-1.02)mm external radius and 7.56mm (+/-0.75) internal radius, and
      material properties with a mean E of 14.9GPa (+/-2.6) and a mean nu of 0.26 (+/
      0.08).

PMID- 22857947
TI  - Platelet aggregation at discharge: a useful tool in acute coronary syndromes?
AB  - INTRODUCTION: Inhibition of platelet aggregation appears two hours after the
      first dose of clopidogrel, becomes significant after the second dose, and
      progresses to a steady-state value of 55% by day seven. Low response to
      clopidogrel has been associated with increased risk of stent thrombosis and
      ischemic events, particularly in the context of stable heart disease treated by
      percutaneous coronary intervention. OBJECTIVE: To stratify medium-term prognosis
      of an acute coronary syndrome (ACS) population by platelet aggregation. METHODS:
      We performed a prospective longitudinal study of 70 patients admitted for an ACS
      between May and August 2009. Platelet function was assessed by ADP-induced
      platelet aggregation using a commercially available kit (Multiplate((r))
      analyzer) at discharge. The primary endpoint was a combined outcome of mortality,
      non-fatal myocardial infarction, or unstable angina, with a median follow-up of
      136.0 (79.0-188.0) days. RESULTS: The median value of platelet aggregation was
      16.0U (11.0-22.5U) with a maximum of 41.0U and a minimum of 4.0U (normal value
      according to the manufacturer: 53-122U). After ROC curve analysis with respect to
      the combined endpoint (AUC 0.72), we concluded that a value of 18.5U conferred a
      sensitivity of 75.0% and a specificity of 68% to that result. We therefore
      created two groups based on that level: group A - platelet aggregation <18.5U,
      n=44; and group B - platelet aggregation >=18.5U, n=26. The groups were similar
      with respect to demographic data (age 60.5 [49.0-65.0] vs. 62.0 [49.0-65.0]
      years, p=0.21), previous cardiovascular history, and admission diagnosis. There
      were no associations between left ventricular ejection fraction, GRACE risk
      score, or length of hospital stay and platelet aggregation. The groups were also
      similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6
      vs. 46.2%, p=0.15) and statin therapy. The variability in platelets and
      hemoglobin was also similar between groups. Combined event-free survival was
      higher in group A (96.0 vs. 76.7%, log-rank p<0.01). Platelet aggregation higher
      than 18.5U was an independent predictor of the combined event (HR 6.75, 95% CI
      1.38-32.90, p=0.02). CONCLUSION: In our ACS population platelet aggregation at
      discharge was a predictor of medium-term prognosis.

PMID- 22857948
TI  - Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese
      population.
AB  - BACKGROUND: Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic
      expressions, of which sudden cardiac death is the most feared. A genetic
      diagnosis is essential to identify subjects at risk in each family. The spectrum
      of disease-causing mutations in the Portuguese population is unknown. METHODS:
      Seventy-seven unrelated probands with hypertrophic cardiomyopathy were
      systematically screened for mutations by PCR and sequencing of five sarcomeric
      genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was
      performed in most patients. RESULTS: Thirty-four different mutations were
      identified in 41 (53%) index patients, 71% with familial hypertrophic
      cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22
      different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%)
      and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3
      and/or MYH7. Additionally, 276 relatives were screened, leading to the
      identification of a mean of three other affected relatives for each pedigree with
      the familial form of the disease. CONCLUSIONS: Disease-associated mutations were
      identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea
      that rarely studied genes may be implicated in sporadic forms. Private mutations
      are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3
      and MYH7 accounted for most cases of sarcomere-related disease. Multiple
      mutations in these genes may occur, which highlights the importance of screening
      both. The detection of novel mutations strongly suggests that all coding regions
      should be systematically screened. Genotyping in hypertrophic cardiomyopathy
      enables a more precise diagnosis of the disease, with implications for risk
      stratification and genetic counseling.

PMID- 22857949
TI  - Accumulation of linear mitochondrial DNA fragments in the nucleus shortens the
      chronological life span of yeast.
AB  - Translocation of mitochondrial DNA (mtDNA) fragments to the nucleus and insertion
      of those fragments into nuclear DNA has been observed in several organisms
      ranging from yeast to plants and mammals. Disruption of specific nuclear genes by
      de novo insertions of mtDNA fragments has even been linked to the initiation of
      several human diseases. Recently, we demonstrated that baker's yeast strains with
      high rates of mtDNA fragments migrating to the nucleus (yme1-1 mutant) exhibit
      short chronological life spans (CLS). The yeast CLS is determined by the survival
      of non-dividing cell populations. Here, we show that lack of the non-homologous
      end-joining enzyme DNA ligase IV (DNL4) can rescue the short CLS of the yme1-1
      mutant. In fission yeast, DNA ligase IV has been shown to be required for the
      capture of mtDNA fragments during the repair of double-stranded DNA breaks in
      nuclear DNA. In further analyses using pulse field gel and 2D gel electrophoresis
      we demonstrate that linear mtDNA fragments with likely nuclear localization
      accumulate in the yme1-1 mutant. The accumulation of the linear mtDNA fragments
      in the yme1-1 mutant is suppressed when Dnl4 is absent. We propose that the
      linear nuclear mtDNA fragments accelerate the aging process in the yme1-1 mutant
      cells by possibly affecting nuclear processes including DNA replication,
      recombination, and repair as well as transcription of nuclear genes. We speculate
      further that Dnl4 protein has besides its function as a ligase also a role in DNA
      protection. Dnl4 protein may stabilize the linear mtDNA fragments in the nucleus
      by binding to their physical ends. In the absence of Dnl4 protein the linear
      fragments are therefore unprotected and possibly degraded by nuclear nucleases.

PMID- 22857950
TI  - CCL5 and CCL20 mediate immigration of Langerhans cells into the epidermis of full
      thickness human skin equivalents.
AB  - Epidermal Langerhans cells (LC) play a key role in initiation and regulation of
      immune responses. Whereas LC migration out of the epidermis upon environmental
      assault is extensively studied, the mechanisms involved in the (re)population of
      the epidermis with LC are poorly understood. Here, we investigated the
      immigration of LC derived from the human MUTZ-3 cell line (MUTZ-LC) into the
      epidermis of a full thickness skin equivalent, comprising a fully differentiated
      epidermis on a fibroblast-populated dermis. MUTZ-LC were used to determine which
      epidermis-derived chemokines play a role in mediating LC trans-dermal migration
      into the epidermis. We found evidence for a role of keratinocyte-derived CCL5 and
      CCL20 in the chemo-attraction of MUTZ-LC. Neutralizing antibodies against CCL5
      and CCL20 blocked LC migration towards keratinocytes. Secretion of these two
      chemokines was associated with incorporation of MUTZ-LC into the epidermis of
      full thickness skin equivalents. In conclusion, our findings suggest that
      epidermis derived CCL5 and CCL20 are pivotal mediators in recruitment of LC into
      the epidermis.

PMID- 22857952
TI  - Building synthetic cell systems from the ground up.

PMID- 22857953
TI  - Viral disease of cattle. Foreword.

PMID- 22857951
TI  - Molecular basis for specific regulation of neuronal kinesin-3 motors by
      doublecortin family proteins.
AB  - Doublecortin (Dcx) defines a growing family of microtubule (MT)-associated
      proteins (MAPs) involved in neuronal migration and process outgrowth. We show
      that Dcx is essential for the function of Kif1a, a kinesin-3 motor protein that
      traffics synaptic vesicles. Neurons lacking Dcx and/or its structurally conserved
      paralogue, doublecortin-like kinase 1 (Dclk1), show impaired Kif1a-mediated
      transport of Vamp2, a cargo of Kif1a, with decreased run length. Human disease
      associated mutations in Dcx's linker sequence (e.g., W146C, K174E) alter
      Kif1a/Vamp2 transport by disrupting Dcx/Kif1a interactions without affecting Dcx
      MT binding. Dcx specifically enhances binding of the ADP-bound Kif1a motor domain
      to MTs. Cryo-electron microscopy and subnanometer-resolution image reconstruction
      reveal the kinesin-dependent conformational variability of MT-bound Dcx and
      suggest a model for MAP-motor crosstalk on MTs. Alteration of kinesin run length
      by MAPs represents a previously undiscovered mode of control of kinesin transport
      and provides a mechanism for regulation of MT-based transport by local signals.

PMID- 22857954
TI  - Tarsal tunnel syndrome: A literature review.
AB  - BACKGROUND: Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the
      posterior tibial nerve or its branches within its fibro-osseous tunnel beneath
      the flexor retinaculum on the medial side of the ankle. It is a rare but
      important condition which is regularly under diagnosed leading to a range of
      symptoms affecting the plantar aspect of the foot. Management of this entrapment
      neuropathy remains a challenge and we have therefore reviewed the published
      literature in an attempt to clarify aspects of initial presentation,
      investigation and definitive treatment including surgical decompression. We also
      assessed the continuing controversial role of electrodiagnostic techniques in its
      diagnosis. CONCLUSION: Recommendations from literature: Excellent results with
      decompression in selected patients. To prevent nerve fibrosis, decompression
      should be performed early. Remain aware of false negative NCS (under-diagnosing
      of those with symptoms but 'normal' NCS. Role of NCS remains controversial with
      inability to predict which cases respond to decompression. Poor outcome may be
      due to nerve fibrosis.

PMID- 22857955
TI  - Functional outcome of ankle fracture patients treated with biodegradable
      implants.
AB  - BACKGROUND: Biodegradable devices have been developed to overcome the
      disadvantages of metallic implants especially the need for their subsequent
      removal, though they have their own drawbacks like poor mechanical properties and
      tissue reactions. Aim of this prospective study was to access the outcome of
      bimalleolar fractures fixed with biodegradable plates and screws. METHODS: A
      prospective study was conducted between July 2006 and November 2008 comprising of
      sixteen patients with unilateral bimalleolar fractures. Fibula fractures were
      fixed with biodegradable plates and medial malleoli with screws. Patients were
      followed at two weeks, six weeks, three months, six months, twelve months and
      eighteen months. Final evaluation was done using Olerud Molander ankle score.
      RESULTS: Six patients had excellent results; four patients had good results and
      six patients had fair performance. No patient in this series had a poor outcome.
      One patient had both pain and swelling at 14 weeks postoperatively which settled
      down with debridement and antibiotics. None of the patients needed implant
      removal. CONCLUSION: Biodegradable plates and screws when used to fix bimalleolar
      fracture along with restricted weight bearing, provide satisfactory fracture
      healing, good functional results and reduce the need of implant removal.

PMID- 22857956
TI  - UK national survey of venous thromboembolism prophylaxis in ankle fracture
      patients treated with plaster casts.
AB  - BACKGROUND: Ankle fractures are one of the commonest orthopaedic injuries. A
      substantial proportion of these are treated non-operatively at outpatient clinics
      with cast immobilization. We conducted this survey to assess the current practice
      in UK regarding thromboembolism prophylaxis in these patients. METHODS: A
      telephonic survey was carried out on junior doctors within orthopaedic
      departments of 56 hospitals across the UK. A questionnaire was completed
      regarding venous thromboembolism risk assessment, prophylaxis, hospital
      guidelines, etc. RESULTS: 84% (n=47) hospitals did not routinely use any
      prophylaxis for these patients, while 7% (n=4) hospitals used chemo-prophylaxis.
      Only 5.3% (n=3) hospitals had DVT prophylaxis guidelines regarding these patients
      while other 9% (n=5) hospitals were in process of developing such guidelines. In
      64% (n=36) hospitals, no formal DVT risk assessment was carried out. CONCLUSION:
      A large variation exists across NHS hospitals and a poor risk assessment is being
      carried out in these patients. Development of local guidelines and extension of
      national guidelines to include high risk outpatients may improve the situation.

PMID- 22857957
TI  - Preliminary results of 97 percutaneous gastrocnemius muscular lengthening
      operations in neurologically healthy children with an equinus contracture.
AB  - BACKGROUND: We report a gastrocnemius lengthening in neurologically healthy
      children, whose gastrocnemius equinus could not be corrected non-operatively.
      METHODS: Fifty-five children with an equinus contracture were included in this
      study. Ninety-seven operations were performed in these patients. The mean age was
      11.5 years [6-16] and sixty percent of the patients were male. After 12 weeks we
      measured dorsiflexion post-surgery and after one year all parents of patients
      were telephoned and asked about their satisfaction with the result of the
      surgical treatment. Persistence of pre-operative complaints and complications
      were evaluated. RESULTS: Ankle dorsiflexion significantly improved by more than
      11 degrees  post-surgery compared with preoperative (p=0.01). The mean
      satisfaction was 8.0 [4-10] on a 10-point VAS scale. Except one complication of
      ankle fracture during surgery, no other clinically relevant complications were
      observed. At follow up 50% of the patients have no complaints, 47% reported an
      improvement but some persisting complaints and 3% of the patients report no
      improvement. CONCLUSION: Percutaneous muscular gastrocnemius lengthening can be
      used to correct gastrocnemius equinus in otherwise healthy children, who have not
      benefited from prior nonsurgical treatment.

PMID- 22857958
TI  - Closed reduction and percutaneous cannulated screws fixation of displaced intra
      articular calcaneus fractures.
AB  - BACKGROUND: Displaced intra-articular calcaneal fractures remain a therapeutic
      challenge due to fracture complexity and different treatment options. One of the
      adverse effects of operative treatment is secondary damage to soft tissues. To
      avoid soft tissue complications, several less invasive procedures have been
      introduced. The most frequently used minimally invasive technique is closed
      reduction of fracture and percutaneous cannulated screws fixation. METHOD: This
      study evaluates the medium-term outcome of a new technique of percutaneous
      treatment in 60 cases operated in Al-Razi orthopedic hospital in Kuwait in the
      period from 2007 to 2009. The described technique applies the principle of closed
      manipulation with new reduction method using a medial subperiosteal tunnel to
      manipulate the fragments. The technique involves new method of distribution of
      screws required to fix the fracture. RESULTS: According to the American
      Orthopedic Foot and Ankle Society Hind foot Score, 38.3% of all cases (22 cases)
      had excellent results, 41% good (25 cases), fair results in 15% (9 cases), and
      poor results in 5% (4 cases). The overall satisfactory results (excellent and
      good) were 79.3%. CONCLUSION: The technique is suitable for most types of intra
      articular fractures especially in patients with compromised soft tissues in which
      open reduction and internal fixation is contraindicated.

PMID- 22857959
TI  - Reliability of metatarsus adductus angle and correlation with hallux valgus.
AB  - BACKGROUND: Metatarsus adductus is a common congenital foot deformity. Variable
      prevalence values were reported using different techniques in different
      populations. Numerous radiological measurements have been proposed to assess this
      deformity with a paucity of studies reporting the reliability of these methods.
      The metatarsus adductus angle was shown to correlate with the severity of hallux
      abductovalgus in normal feet and preselected populations of juvenile hallux
      valgus. MATERIALS AND METHODS: Weight bearing dorsoplantar radiographs of 150
      feet were examined for 5 angles commonly used in assessing metatarsus adductus:
      angle between the second metatarsus and the longitudinal axis of the lesser
      tarsus (using the 4th or 5th metatarso-cuboid joint as a reference), Engel's
      angle and modified Engle's angle. The prevalence of metatarsus adductus was
      assessed according to published criteria for different techniques. Inter and
      intra-observer reliabilities of these angles were evaluated on 50 X-rays. Linear
      regression tests were used to assess the correlation between hallux valgus and
      different angles used in assessing metatarsus adductus. RESULTS: Intraclass
      correlation coefficients were high for intra- as well as inter-observer
      reliability for the 5 angles tested. Prevalence of metatarsus adductus ranged (45
      70%) depending on the angle used in the same population. Only the metatarsus
      adductus angle using the 4th metatarso-cuboid joint as a reference demonstrated
      significant correlation between metatarsus adductus and hallux abductovalgus
      angles. CONCLUSION: Five techniques commonly used in assessing metatarsus
      adductus demonstrated high inter and intra-observer reliability values.
      Prevalence of metatarsus adductus and the correlation between the severity of
      this deformity and hallux valgus angle is sensitive to the assessment method.

PMID- 22857960
TI  - Bohler's angle - What is normal in the uninjured British population?
AB  - Bohler's angle is a radiographic parameter widely used in the detection and
      assessment of fractures of the os calcis. The normal range in the uninjured
      British adult population has not previously been established. We analysed 128
      lateral radiographs without fracture in order to establish the true value of
      Bohler's angle. Analysis was performed with respect to age, sex and laterality.
      Interobserver reliability was also assessed. The mean angle was 36.4 degrees  (SD
      4.2 degrees , range 24.7-48.9 degrees ). The normal range was 28.2-44.5 degrees ,
      which incorporates 95% of subjects. There was no difference with respect to age,
      sex or laterality. Agreement between independent observers was good
      (interobserver correlation coefficient=0.72), although there was disagreement of
      >5 degrees  in 40.9% of cases. Given the wide range of normal values we recommend
      a comparative radiograph of the contralateral side if the presence of fracture is
      ambiguous.

PMID- 22857961
TI  - A new limb-salvaging technique for the treatment of late stage complicated
      Charcot foot deformity: Two-staged Boyd's operation.
AB  - BACKGROUND: Depending on the stage of disease, several operative and non
      operative treatment options exist for diabetic patients with Charcot foot
      deformity. In the early stages of the disease, the most effective treatment is
      total-contact cast application. In patients with multiple bone fractures and
      deformations, surgical interventions are generally required for the
      reconstruction of foot architecture. Exostectomy, osteotomy, arthrodesis, and
      internal-external fixation are some of these operative methods. However,
      recurrence of ulcer and infection is very likely following these surgical
      procedures. If the lesion and infection reach to midfoot and hindfoot region, a
      major amputation is usually required for treatment. METHODS: We have been
      performing Boyd's operation for the last 10 years in diabetic foot patients who
      had complicated lesions in midfoot and hindfoot regions. Furthermore, since 2004,
      we have been doing the same operation for complicated Charcot foot deformities.
      So far, we have treated 11 patients. RESULTS: The mean age of the patients was
      53.4+/-10.2 years, and the mean duration of diabetes mellitus (DM) was 17.5+/-7.2
      years. All patients had chronic infections with fractures of the tarsal bones for
      at least 2 years. Durable wound coverage and ankylosis were achieved in all
      patients with two-staged Boyd's operation. No recurrence is detected in any of
      the patients during mean post-operative follow-up period of 2.1+/-0.8 years.
      CONCLUSION: Boyd's operation is a reliable option for the treatment of patients
      with late stage Chatcot foot deformity.

PMID- 22857962
TI  - A comparative study of bone shortening and bone loss with use of saw blades
      versus burr in hallux valgus surgery.
AB  - BACKGROUND: The aim of this study was to assess bone loss and thickness of the
      cut with the use of a burr in percutaneous hallux valgus surgery. METHODS: Twelve
      blocks of saw bone were used. Cuts of same depth were made in each block with two
      different saw blades and a burr. Each block was assessed for bone loss and
      thickness of the cut. RESULTS: There was statistically significant (p<0.05)
      increased bone loss and thickness of the cuts with the use of a burr as compared
      to use of two different saw blades. The use of a burr resulted in threefold
      increased loss of bone material and fourfold increase in the thickness of the cut
      as compare to use of two different saw blades. CONCLUSION: The metatarsal
      shortening is a risk factor in percutaneous hallux valgus surgery with the use of
      a burr.

PMID- 22857963
TI  - Internet information quality for ten common foot and ankle diagnoses.
AB  - BACKGROUND: Patients use the Internet regularly to access health-related
      information. This study's goal was to assess the quality and content of Internet
      based information for common foot and ankle diagnoses. METHODS: We identified the
      ten most common foot and ankle diagnoses in our academic foot and ankle practice.
      Ten websites for each diagnosis were identified using two large Internet search
      engines. A custom grading form was used to determine website quality, based upon
      the Health On the Net Foundation (HON) principles, and information content. Four
      independent reviewers graded each website. RESULTS: One hundred thirty-six unique
      websites were reviewed. Average HON score was 62.4 (range, 52.3-68.8) and content
      score was 49.7 (range, 33.8-62.1) out of a maximum of 100. Interobserver
      variability was low. CONCLUSIONS: The overall quality of Internet information for
      common foot and ankle diagnoses is variable, raising concerns about what
      information is currently available to patients.

PMID- 22857964
TI  - Motion of the fibula relative to the tibia and its alterations with syndesmosis
      screws: A cadaver study.
AB  - BACKGROUND: The motion of the fibula in relation to the tibia is coupled on the
      motion of the talus in the ankle joint. Several authors investigated this motion
      with different methods. An injury of the elastic fixation of the fibula to the
      tibia and its treatment with the syndesmotic set screw has an impact on this
      motion. METHODS: The motion of the fibula relative to the tibia was measured in
      eight embalmed human above the knee amputated cadaver specimens using a 3D-motion
      analysis system. The relative motion was measured from 50 degrees  of plantar
      flexion to 30 degrees  of dorsiflexion. Experiments were performed in the
      following conditions: without fixation and intact ligaments, after sectioning of
      the four syndesmotic ligaments and the interosseous membrane, and application of
      either a tricortical screw, or a quadricortical screw or two quadricortical
      screws. RESULTS: Concordant movements of the lateral malleolus were a medial
      translation during plantar flexion, external rotation around the sagittal axis
      during plantar and dorsiflexion. The motion of the proximal fibula was smaller
      and more variable than in the distal part. After sectioning of the syndesmosis
      the range of motion, compared to the intact state increased, particularly in
      translation along the transversal (118%), sagittal (160%) and the longitudinal
      (136%) axis and in axial rotation (145%). Syndesmotic screws reduced the range of
      motion in transversal (p<0.006) and sagittal translation (p<0.011) and axial
      rotation. CONCLUSION: The small relative motion of the tibia and fibula is
      increased by syndesmotic injuries. Syndesmosis screws significantly limit this
      increased relative motion below physiologic values, which makes it necessary to
      remove the screws before flexion in the ankle joint is performed.

PMID- 22857965
TI  - Metatarsal extension osteotomy without plantar aponeurosis release in cavus feet.
      The effect on claw toe deformity a radiographic assessment.
AB  - BACKGROUND: This study reviewed patients undergoing correction of cavus foot
      deformity by metatarsal extension osteotomy with preservation of the plantar
      aponeurosis, and assessed the correction achieved of the claw deformity of the
      toe by radiographic assessment. METHOD: 15 patients (18 feet) were reviewed
      clinically and radiographically. All feet required extension osteotomy of the
      first metatarsal and four patients (5 feet) had extension osteotomy of the first
      to fourth metatarsals. Hallux extension angle in relation to the 1st metatarsal
      and in relation to the ground was measured in all feet to estimate the degree of
      clawing of the hallux. RESULTS: 13 patients (15 feet) were satisfied with the
      outcome of their surgery and also the appearance of their foot. The mean
      radiographic change in the hallux extension angle in relation to the 1st
      metatarsal was 16 degrees , and in relation to the ground was 7 degrees . These
      changes were statistically significant. CONCLUSION: Our results indicate an
      improvement in the claw toe deformity and we recommend preservation of the
      plantar aponeurosis in corrective surgery for cavus foot.

PMID- 22857966
TI  - The use of surgeon-performed ultrasound assessment in a foot and ankle clinic.
AB  - BACKGROUND: We describe the first reported use of ultrasound examination
      performed by an orthopaedic surgeon in the setting of a foot and ankle clinic.
      METHODS: The senior author attended a course in musculoskeletal ultrasound and
      performed 100 examinations each checked against the results from a consultant
      radiologist. Records were kept of all examinations performed in the clinic over a
      6-month period with results. RESULTS: Of the 622 patients seen, 91 had an
      ultrasound scan and 36 had guided injections. All patients had one hospital
      attendance spared, for most two. Time saved on the treatment pathway per patient
      was on average 6 weeks. CONCLUSION: Ultrasound assessment performed by a
      clinician during an outpatient clinic appointment reduces delay in treatment and
      cuts costs by reducing patient episodes.

PMID- 22857967
TI  - Soft tissue injury to the sole of the foot secondary to a retained AV impulse
      foot pump.

PMID- 22857969
TI  - Owens et al. "Morton's neuroma: Clinical testing and imaging in 76 feet, compared
      to a control group" [Foot and Ankle Surgery 17 (September (3)) 2011].

PMID- 22857970
TI  - A rare case of closed pantalar dislocation combined with Lisfranc's injury--The
      unusual complex.
AB  - Closed pantalar dislocation with associated Lisfranc's injury is a very rare
      injury. We report a rare case of such injury. Our patient had fall from height
      and presented with closed pantalar dislocation with Lisfranc's injury of the left
      foot and other multiple injuries. He was immediately operated and dislocation was
      reduced and was stabilised with multiple Kirschner wires. At the end of 1 year
      follow up, he had an AOFAS score of 78 and had painless ankle movements. To the
      best of our knowledge, this is the first case reported with such a rare
      combination of injury.

PMID- 22857971
TI  - Resection of bilateral massive Achilles tendon xanthomata with reconstruction
      using a flexor hallucis longus tendon transfer and Bosworth turndown flap: A case
      report and literature review.
AB  - Tumours of the Achilles tendon are rare. Reconstruction of the large defect
      following excision, however, is often a challenge and is sometimes a factor in
      deciding against operative treatment of a benign lesion. We report a case of
      excision of bilateral Achilles tendon xanthomata, with reconstruction using a
      flexor hallucis longus tendon transfer and Bosworth turndown flap.

PMID- 22857972
TI  - Osteosarcoma of navicular bone. En bloc excision and salvage of the foot.
AB  - AIM: To present foot salvage for osteosarcoma of the navicular bone with en bloc
      resection and reconstruction using bone allograft and talus-cuneiform
      arthrodesis. PATIENT AND SURGICAL TECHNIQUE: A 20 year-old male with a history of
      osteosarcoma of the distal femur presented to our department 5 years later with a
      metastatic lesion of the navicular bone of the contralateral foot. The patient
      received 4 cycles of neo-adjuvant chemotherapy with satisfactory response. Tumor
      shrinkage allowed en bloc excision of the navicular bone with clear margins.
      Reconstruction was done using a tricortical allograft and talus-allograft
      cuneiform arthrodesis, secured with a mini-fracture plate (Synthes). Weight
      bearing protection was advised for 2 months and partial weight bearing for
      another 4 months. Patient received 4 cycles of adjuvant chemotherapy. RESULTS:
      Three years postoperatively, the patient was free of local recurrence or distant
      metastasis. There were no signs of allograft resorption, fracture or non union.
      The patient was asymptomatic and full weight bearing. Ankle and subtalar joint
      motion was within normal limits. CONCLUSION: Foot salvage after excision of
      osteosarcoma of the navicular bone could be possible if en bloc resection of the
      lesion could be performed. Talus-cuneiform fusion with allograft interposition is
      a viable reconstructive option.

PMID- 22857973
TI  - Talonavicular synostosis with lateral ankle instability--A case report and review
      of the literature.
AB  - Talonavicular coalition is a rare autosomal recessive congenital anomaly that is
      usually asymptomatic and detected incidentally on radiographs. It is associated
      with symphalangism, clinodactyly, a great toe that is shorter than the second
      toe, clubfoot, calcaneonavicular coalition, talocalcaneal coalition and a ball
      and-socket ankle joint. The authors present a review of the literature and case
      report of a patient with complete osseous talonavicular coalition, talocalcaneal
      coalition and lateral ankle instability which was successfully treated with
      subtalar fusion and lateral ligament reconstruction.

PMID- 22857975
TI  - Transmission of avian-origin canine influenza viruses A (H3N2) in cats.

PMID- 22857974
TI  - Technologies for global health.

PMID- 22857976
TI  - Analyses of intestinal commensal Escherichia coli strains from wild boars suggest
      adaptation to conventional pig production conditions.
AB  - To test the hypothesis that Escherichia coli populations have adapted to
      conventional pig production practices, we comparatively tested intestinal
      commensal E. coli from wild boars versus isolates from domestic pigs by analyzing
      virulence-associated factors, adhesion, and metabolic activities. Virulence
      associated genes typical for intestinal pathogenic E. coli (inVAGs) were
      sporadically detected among E. coli from wild boars except the adhesion-related
      gene paa and the enterotoxin-encoding gene astA. In contrast, several VAGs
      typical for extraintestinal pathogenic E. coli (exVAGs) were common in E. coli
      from wild boars. The exVAG chuA occurred more often in E. coli from wild boars
      compared to E. coli from domestic pigs. 23.5% of E. coli from wild boars belonged
      to EcoR group B2 which is higher than observed for E. coli from clinically
      healthy domestic pigs. Furthermore, E. coli from wild boars were more efficient
      in fermentation of carbohydrate sources (dulcitol, inositol, d-sucrose, d
      tagatose), and adhered better to the intestinal porcine epithelial cell line IPEC
      J2. In conclusion, our findings point towards an adaptation of porcine intestinal
      E. coli to a specific intestinal milieu caused by different animal living
      conditions.

PMID- 22857977
TI  - Viral tropism and pathology associated with viral hemorrhagic septicemia in
      larval and juvenile Pacific herring.
AB  - Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in
      wild Pacific herring, a species of economic value, in the Northeast Pacific
      Ocean. Young of the year herring are particularly susceptible and can be carriers
      of the virus. To understand its pathogenesis, tissue and cellular tropisms of
      VHSV in larval and juvenile Pacific herring were investigated with
      immunohistochemistry, transmission electron microscopy, and viral tissue titer.
      In larval herring, early viral tropism for epithelial tissues (6d post-exposure)
      was indicated by foci of epidermal thickening that contained heavy concentrations
      of virus. This was followed by a cellular tropism for fibroblasts within the fin
      bases and the dermis, but expanded to cells of the kidney, liver, pancreas,
      gastrointestinal tract and meninges in the brain. Among wild juvenile herring
      that underwent a VHS epizootic in the laboratory, the disease was characterized
      by acute and chronic phases of death. Fish that died during the acute phase had
      systemic infections in tissues including the submucosa of the gastrointestinal
      tract, spleen, kidney, liver, and meninges. The disease then transitioned into a
      chronic phase that was characterized by the appearance of neurological signs
      including erratic and corkscrew swimming and darkening of the dorsal skin. During
      the chronic phase viral persistence occurred in nervous tissues including
      meninges and brain parenchymal cells and in one case in peripheral nerves, while
      virus was mostly cleared from the other tissues. The results demonstrate the
      varying VHSV tropisms dependent on the timing of infection and the importance of
      neural tissues for the persistence and perpetuation of chronic infections in
      Pacific herring.

PMID- 22857978
TI  - Disseminated systemic mycosis in Veiled chameleons (Chamaeleo calyptratus) caused
      by Chamaeleomyces granulomatis.
AB  - The aim of the examination was to gain knowledge on the incidence of
      Chamaeleomyces granulomatis mycosis in Veiled chameleons (Chamaeleo calyptratus),
      a disease which has recently been described as a single outbreak in a zoo
      collection. During a time period of 26 months (September 2009-November 2011) 18
      Veiled chameleons presented at the clinic for various reasons were examined for
      the presence of C. granulomatis. Swabs were taken from tongue and skin lesions of
      live chameleons and from internal granulomas of deceased chameleons. Mycological
      culture was performed on Sabouraud dextrose and Potato dextrose agar as described
      previously. For the first time, the obtained isolates were screened for
      susceptibility towards different antifungal drugs by use of agar diffusion
      testing. Fungal species were determined by amplification with different primers,
      as reported before, and sequencing of parts of the 28S rDNA gene, the 18S rDNA
      gene, internal transcribed spacer region-1 DNA and 5.8S rDNA gene. Ten cases of
      disseminated mycosis caused by C. granulomatis were thus documented. These
      animals were kept in nine different collections of differing owners. Common
      findings in diseased chameleons were disseminated mycosis, glossitis and
      dermatitis. Although all isolates were tested sensitive to terbinafine and
      nystatin. The results of this study clearly show, contrary to a recently
      published single outbreak in a zoo collection, that disseminated mycosis caused
      by C. granulomatis in Veiled chameleons is, a common and often fatal infectious
      disease in this species. The routes of infection or treatment options are still
      unknown and need further investigation.

PMID- 22857979
TI  - Successful effect of tocilizumab in anti-TNF-alpha-induced palmoplantar
      pustulosis in rheumatoid arthritis.
AB  - Anti-tumour necrosis factor-alpha (TNF-alpha) agents are effective drugs used in
      several chronic inflammatory diseases such as rheumatoid arthritis (RA).
      Psoriasiform lesions, including palmoplantar pustulosis, have been described
      following anti-TNF-alpha therapy. These lesions often resolve with topical
      therapy with or without discontinuation of these drugs. However, in some cases,
      psoriasiform lesions may persist despite anti-TNF-alpha withdrawal. We report on
      two RA patients treated with adalimumab (ADA) who developed palmoplantar pustular
      despite dermatological treatment and ADA discontinuation. Tocilizumab (TCZ)
      therapy was initiated because of persistence of skin lesions and flare of the
      disease. Following treatment with this drug, complete resolution of the
      dermatological lesions and induction of remission of RA was achieved. To the best
      of our knowledge, management of palmoplantar pustulosis due to TNF-alpha agents
      with TCZ leading to both improvement of the disease and resolution of the
      cutaneous lesions has not previously been reported.

PMID- 22857980
TI  - [Copayment can also be a social measure].
AB  - Psychology shows that what is free is poorly valued. Free of cost national health
      systems may become blocked due to misuse and may even become unfeasible.
      Copayment already exist in Spain. It was introduced in pharmaceutical
      prescriptions as a solidarity measure. This copayment has generated abuses. Its
      introduction has always been seen as a co-financing action to the system or as a
      discouraging measure to avoid misuse. The truly solidarity action is a proper
      organization of a copayment system as a social measure together with efficiency
      measures and rational use of health resources by all participant actors in the
      system: managers, professionals and users.

PMID- 22857981
TI  - Serum biomarkers of neurologic injury in cardiac operations.
AB  - Assessment of subtle neurocognitive decline after surgical procedures has been
      hampered by heterogeneous testing techniques and a lack of reproducibility. This
      review summarizes the sensitivity and specificity of biomarkers of neurologic
      injury to determine whether they can be applied in the postoperative period to
      accurately predict neurocognitive decline. Creatine kinase-brain type, neuron
      specific enolase, and S100B can be released into serum during operations by
      extracranial sources. Glial fibrillary acidic protein is a sensitive marker, and
      there are extracranial sources that are antigenically different from the brain
      derived form. Serum levels of tau protein after acute neurologic injury do not
      reliability correlate with incidence.

PMID- 22857982
TI  - Late outcomes in patients undergoing aortopulmonary window for pulmonary
      atresia/stenosis and major aortopulmonary collaterals.
AB  - BACKGROUND: Pulmonary atresia with ventricular septal defect (PA/VSD) and major
      aortopulmonary collateral arteries (MAPCAs) is a complex form of congenital heart
      defect. One identifiable subset has small (<2.5 mm) intrapericardial branch
      pulmonary arteries that are (1) confluent, (2) have normal arborization, and (3)
      have dual-supplied collateral vessels. When this anatomy is associated with
      limited pulmonary blood flow, the patients are candidates for creation of an
      aortopulmonary window to stimulate growth of the pulmonary arteries. The purpose
      of this study was to review our experience with creation of an aortopulmonary
      window as the initial palliative procedure. METHODS: This was a retrospective
      review of our surgical experience with 35 children undergoing aortopulmonary
      window creation from 2002 to 2011. Patients were identified by preoperative
      cardiac catheterization to define the cardiac and pulmonary artery anatomy.
      RESULTS: There was no mortality in 35 patients undergoing aortopulmonary window
      creation. These patients have subsequently undergone 78 cardiac procedures (with
      2 operative mortalities). Eighteen of these patients have achieved complete
      repair, 4 patients in a second procedure, 6 patients in a third procedure, 5
      patients in a fourth procedure, and 3 patients in a fifth procedure. CONCLUSIONS:
      The data demonstrate that patients can undergo creation of an aortopulmonary
      window with excellent early results. Few patients were amenable to complete
      repair at the second operation, and most required multiple reoperations to
      recruit sufficient arborization. We interpret these counterintuitive results to
      suggest that hypoplastic central pulmonary arteries and diminished pulmonary
      blood flow are markers for a less well developed pulmonary vascular bed.

PMID- 22857985
TI  - Oral mucosa and urethroplasty: it's time to change.

PMID- 22857986
TI  - Ray-tracing intraocular lens power calculation using anterior segment optical
      coherence tomography measurements.
AB  - PURPOSE: To assess the efficiency of ray-tracing intraocular lens (IOL) power
      calculation with anterior segment optical coherence tomography (AS-OCT) in normal
      eyes with cataract. SETTING: Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan.
      DESIGN: Case series. METHODS: The study comprised consecutive patients who had
      cataract surgery and obtained a corrected visual acuity of 0.15 logMAR or better
      postoperatively. Preoperatively, Placido topography and AS-OCT measurements were
      taken during a routine examination. The predicted postoperative refractions were
      obtained using 3 methods: the SRK/T formula with autokeratometry, ray-tracing
      calculation with Placido topography data, and ray-tracing calculations with AS
      OCT measurement of both corneal surfaces. The refractive errors from the manifest
      refraction spherical equivalent were compared 1 month postoperatively, and the
      effects of corneal eccentricity and posterior corneal curvature were evaluated.
      RESULTS: Seventy patients (102 eyes) were enrolled. There was no significant
      difference in refractive errors (P=.89). The refractive error with the SRK/T
      formula was correlated significantly with corneal eccentricity (P=.0017); the ray
      tracing calculations were unaffected. There was a weak correlation with the
      posterior corneal curvature in the ray-tracing calculations performed with
      Placido topography (P<.0002). CONCLUSION: The accuracy of the ray-tracing IOL
      power calculations using AS-OCT data was comparable to that of the conventional
      formula and minimized the effect of corneal eccentricity and posterior corneal
      curvature.

PMID- 22857983
TI  - Advanced prostate cancer treated with intermittent or continuous androgen
      deprivation in the randomised FinnProstate Study VII: quality of life and adverse
      effects.
AB  - BACKGROUND: Intermittent dosing may reduce the adverse events (AEs) of androgen
      deprivation therapy (ADT). OBJECTIVE: To compare intermittent androgen
      deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health
      related quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: A total of 852
      men with advanced prostate cancer (PCa) were enrolled to receive goserelin
      acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate
      specific antigen (PSA) decreased to <10 ng/ml or by >=50% (<20 ng/ml at baseline)
      were randomised to IAD or CAD. INTERVENTION: In the IAD arm, ADT was resumed for
      at least 24 wk whenever PSA increased >20 ng/ml or above baseline. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: QoL was monitored with a validated Cleary
      30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard
      deviation rule, and repeated measures analysis of variance. AEs and adverse drug
      reactions (ADRs) were analysed by the chi-square test. RESULTS AND LIMITATIONS:
      Median follow-up was 65 mo. Significant differences in QoL emerged in activity
      limitation, physical capacity, and sexual functioning, favouring IAD. No
      significant differences emerged in the prevalence of AEs: 87 patients in the IAD
      arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59),
      with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%)
      dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19
      (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats
      were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7%
      vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the
      IAD arm. CONCLUSIONS: IAD showed benefits in the treatment of advanced PCa with
      respect to QoL. The prevalence of AEs was not significantly lower with IAD. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT00293670.

PMID- 22857987
TI  - The impact of mental practice on stroke patients' postural balance.
AB  - INTRODUCTION: The most common problem in stroke patients is reduced balance and
      derangements of postural control that lead to increase the chance of falling and
      instability during walking. Since physical practice improves balance and postural
      control, it is assumed also that the application of mental practice would be
      useful in enhancing such balance. Mental practice is defined as the cognitive
      rehearsal of a physical skill in the absence of overt physical movements. Factors
      such as similar time between actual execution and mental performance of a task,
      the increase of regional cerebral blood flow and also the vegetative activation,
      all suggest that mental practice imitates physical performance of a task. Thus,
      the main purpose of this study was to investigate the effect of such mental
      practice on postural balance among stroke survivors. METHOD AND MATERIALS: This
      study was implemented as an experimental (interventional), case-control, double
      blind and randomized trial design. A total of 30 subjects (16 males and 14
      females) with necessary arousal, attention and memory functions as their major
      components of mental practice, participated. Subjects' mean ages were 48.1 +/-
      10.5 years. They were divided randomly in two control and experimental groups.
      Timed Get up and Go (TUG) test was used to evaluate the balance of all
      participants. They were assessed before-after treatment and two weeks post
      treatment as research's follow up. The two groups received the same method of
      occupational therapy services, but the experimental group in addition to
      aforementioned occupational therapy, was requested to participate in mental
      practice sessions. RESULTS: Mental practice had a significant effect on postural
      balance in stroke survivors (P=<0.001). CONCLUSION: Mental practice may improve
      postural balance in stroke patients and can be considered for them as a
      beneficial rehabilitative technique.

PMID- 22857988
TI  - Serum biomarkers of spontaneous intracerebral hemorrhage induced secondary brain
      injury.
AB  - Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with a
      high rate of morbidity and mortality. It is now believed that much of this damage
      occurs in the subacute period following the initial insult via a cascade of
      complex pathophysiologic pathways that continues to be investigated. Increased
      levels of certain serum proteins have been identified as biomarkers that may
      reflect or directly participate in the inflammation, blood brain barrier
      disruption, endothelial dysfunction, and neuronal and glial toxicity that occur
      during this secondary period of cerebral injury. Some of these biomarkers have
      the potential to serve as therapeutic targets or surrogate endpoints for future
      research or clinical trials. Others may someday augment current clinical
      techniques in diagnosis, risk-stratification, prognostication, treatment decision
      and measurement of therapeutic efficacy. While much work remains to be done,
      biomarkers show significant potential to expand clinical options and improve
      clinical management, thereby reducing mortality and improving functional outcomes
      in ICH patients.

PMID- 22857989
TI  - Do the paramedian tract neurons in pons take a role as a vertical neural
      integrator in humans?
AB  - Impairment of gaze holding mechanism and gaze-evoked nystagmus (GEN) in the
      vertical plane due to a focal brain lesion is usually caused by a failure of the
      vertical neural integrator, which is known to be localized in the interstitial
      nucleus of the Cajal in the upper midbrain. We report a patient with hemorrhagic
      stroke involving the paramedian pontine tegmentum who presented with vertical GEN
      due to a failure of vertical gaze holding mechanism and unilateral internuclear
      ophthalmoplegia. The possible structure taking a role as a vertical neural
      integrator in this patient might be the paramedian tract (PMT) neuron.

PMID- 22857990
TI  - White matter lesions and depression in patients with Parkinson's disease.
AB  - Depression is frequently associated with Parkinson disease (PD) but neural basis
      is still unclear. In previous studies white matter changes present as signal
      hyperintesities on T2-wighted MRI studies (WMHs) commonly observed in older
      adults have been associated with depressive symptomatology. In this study we
      investigated whether WMHs were associated with depression in PD patients with
      disease onset above the age of 60. Thirty-four patients, with (PD-D) and 25
      without depression (PD-nD), and 30 healthy age- and sex-matched controls were
      analyzed using the Scheltens visual rating scale. Cerebrovascular risk factors
      were similar across groups. Comparing controls and PD patients as a group there
      were no differences in WMHs in any examined regions. However, PD-D group had more
      common frontal WMHs although WMHs score didn't rich statistical significance. The
      same came true for total deep white matter changes comparing those two groups. In
      addition PD-D group had a significantly higher score for periventricular regions
      WMHs comparing with both PD-nD group and controls.PD-D group had significantly
      higher WMHs scores BG regions when compared to controls. The only significance in
      multivariate analyses was shown for periventricular WMHs total score explaining
      the 39% of the variance in the depressive score. Our findings suggest that WMH in
      the deep white matter may contribute to depression in PD.

PMID- 22857991
TI  - The vascular factor in Alzheimer's disease: a study in Golgi technique and
      electron microscopy.
AB  - Although the etiopathological background of Alzheimer's disease (AD) is mostly
      associated with the deposition of Alphabeta-peptide, the hyperphosphorylation of
      tau protein, the synaptic pathology and the mitochondrial alterations, the
      vascular factor may play substantial role in plotting the multifactorial pattern
      of the disease. We attempted to study the blood capillaries in the hippocampus,
      the acoustic, the visual and the parietal cortex in twelve early cases of
      Alzheimer's disease. Samples were processed for Golgi silver impregnation
      technique and electron microscopy. The morphological findings were compared with
      normal controls. The study of the brain capillaries in cases of AD, revealed
      numerous fusiform dilatations, tortuosities, abnormal branching and fusion,
      though the morphometric estimation revealed a decrease of the number of
      capillaries per mm(3) in comparison with normal control brains. The
      ultrastructural study revealed mitochondrial abnormalities in the endothelial
      cells of a substantial number of capillaries and marked degeneration of the
      pericytes. Perivascular microglial proliferation was also prominent in the
      hippocampus and the parietal lobe. Our findings both in Golgi staining and
      electron microscopy plead in favor of the essential role that the microvascular
      alterations may play in the broad pathogenetic spectrum of AD.

PMID- 22857992
TI  - Implications of altered replication fidelity on the evolution and pathogenesis of
      coronaviruses.
AB  - RNA virus evolution results from viral replication fidelity and mutational
      robustness in combination with selection. Recent studies have confirmed the
      impact of increased fidelity on RNA virus replication and pathogenesis; however,
      the impact of decreased fidelity is less defined. Coronaviruses have the largest
      RNA genomes, and encode an exoribonuclease activity that is required for high
      fidelity replication. Genetically stable exoribonuclease mutants will allow
      direct testing of viral mutational tolerance to RNA mutagens and other selective
      pressures. Recent studies support the hypothesis that coronavirus replication
      fidelity may result from a multi-protein complex, suggesting multiple pathways to
      disrupt or alter virus fidelity and diversity, and attenuate pathogenesis.

PMID- 22857993
TI  - Early cell changes and TGFbeta pathway alterations in the aortopathy associated
      with bicuspid aortic valve stenosis.
AB  - Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose
      aetiology is still debated, have focused mainly on severe dilatations. In the
      present study, we aimed to detect earlier signs of aortopathy. Specimens were
      collected from the 'concavity' (lesser curvature) and the 'convexity' (greater
      curvature) of mildly dilated AAs (ascending aortas; diameter <=4 cm) with
      stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas.
      Specimens were submitted to morphometry, immunohistochemistry and differential
      gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype,
      remodelling, MF (myofibroblast) differentiation and TGFbeta (transforming growth
      factor beta) pathway. Smoothelin and myocardin mRNAs decreased in all the samples
      from patients, with the exception of those from BAV convexity, where a change in
      orientation of smoothelin-positive SMCs and an increase of alpha-SMA (alpha
      smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients
      showed both shared and distinct alterations concerning the TGFbeta pathway,
      including an increased TGFbeta and TGFbetaR2 (TGFbeta receptor 2) expression in
      both groups and a decreased TGFbetaR1 expression in BAV samples only. Despite a
      decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN
      (fibronectin) in the BAV convexity, the onset of the expression of the
      corresponding protein in the media was observed in dilated aortas, whereas the
      normal media from donors was negative for this isoform. This discrepancy could be
      related to modifications in the intima, normally expressing ED-A FN and showing
      an altered structure in mild aortic dilatations in comparison with donor aorta.
      Our results suggest that changes in SMC phenotype and, likely, MF
      differentiation, occur early in the aortopathy associated with valve stenosis.
      The defective expression of TGFbetaR1 in BAV might be a constitutive feature,
      while other changes we reported could be influenced by haemodynamics.

PMID- 22857994
TI  - Iridium oxide pH sensor for biomedical applications. Case urea-urease in real
      urine samples.
AB  - This work demonstrates the implementation of iridium oxide films (IROF) grown on
      silicon-based thin-film platinum microelectrodes, their utilization as a pH
      sensor, and their successful formatting into a urea pH sensor. In this context,
      Pt electrodes were fabricated on Silicon by using standard photolithography and
      lift-off procedures and IROF thin films were growth by a dynamic oxidation
      electrodeposition method (AEIROF). The AEIROF pH sensor reported showed a super
      Nerstian (72.9+/-0.9mV/pH) response between pH 3 and 11, with residual standard
      deviation of both repeatability and reproducibility below 5%, and resolution of
      0.03 pH units. For their application as urea pH sensors, AEIROF electrodes were
      reversibly modified with urease-coated magnetic microparticles (MP) using a
      magnet. The urea pH sensor provided fast detection of urea between 78MUM and 20mM
      in saline solution, in sample volumes of just 50MUL. The applicability to urea
      determination in real urine samples is discussed.

PMID- 22857995
TI  - Microfluidic flow fractionation device for label-free isolation of circulating
      tumor cells (CTCs) from breast cancer patients.
AB  - Circulating tumor cells (CTCs) are dissociated from primary tumor and circulate
      in peripheral blood. They are regarded as the genesis of metastasis. Isolation
      and enumeration of CTCs serve as valuable tools for cancer prognosis and
      diagnosis. However, the rarity and heterogeneity of CTCs in blood makes it
      difficult to separate intact CTCs without loss. In this paper, we introduce a
      parallel multi-orifice flow fractionation (p-MOFF) device in which a series of
      contraction/expansion microchannels are placed parallel on a chip forming four
      identical channels. CTCs were continuously isolated from the whole blood of
      breast cancer patients by hydrodynamic forces and cell size differences. Blood
      samples from 24 breast cancer patients were analyzed (half were from metastatic
      breast cancer patients and the rest were from adjuvant breast cancer patients).
      The number of isolated CTCs varied from 0 to 21 in 7.5 ml of blood. Because our
      devices do not require any labeling processes (e.g., EpCAM antibody),
      heterogeneous CTCs can be isolated regardless of EpCAM expression.

PMID- 22857996
TI  - Alimentary disorders in young females with irritable bowel syndrome or ulcerative
      procto-sigmoiditis: a preliminary report.

PMID- 22857997
TI  - Crohn's disease of the large bowel following diagnosis of chronic lymphoid
      leukaemia: a case report.

PMID- 22857998
TI  - On influence of sample loading conditions on peak shape and separation efficiency
      in preparative isocratic counter-current chromatography.
AB  - The cell model theory of CCC is extended to develop analytical solutions for
      various sample loading conditions (non-impulse loading with separate feed stream
      and with the mobile phase flow, impulse and non-impulse periodic loading).
      Equations are presented allowing the simulation of the chromatograms for various
      sample loading conditions. These equations can help to predict the influence of
      sample loading conditions on the separation of a given feed mixture and select a
      suitable compromise between the productivity and the resolution in the isocratic
      preparative and production CCC separations. It is shown that: when the sample
      loading time is about 2% of the mean residence time, the effect of loading time
      can be neglected; the loading time about 20% of the mean residence time seems to
      be quite acceptable; proper selection of the conditions for the sample loading
      can allow increasing the productivity by an order of magnitude ensuring, a
      desirable separation.

PMID- 22857999
TI  - A versatile semi-permanent sequential bilayer/diblock polymer coating for
      capillary isoelectric focusing.
AB  - A sequential surfactant bilayer/diblock copolymer coating was previously
      developed for the separation of proteins. The coating is formed by flushing the
      capillary with the cationic surfactant dioctadecyldimethylammonium bromide
      (DODAB) followed by the neutral polymer poly-oxyethylene (POE) stearate. Herein
      we show the method development and optimization for capillary isoelectric
      focusing (cIEF) separations based on the developed sequential coating.
      Electroosmotic flow can be tuned by varying the POE chain length which allows
      optimization of resolution and analysis time. DODAB/POE 40 stearate can be used
      to perform single-step cIEF, while both DODAB/POE 40 and DODAB/POE 100 stearate
      allow performing two-step cIEF methodologies. A set of peptide markers is used to
      assess the coating performance. The sequential coating has been applied
      successfully to cIEF separations using different capillary lengths and inner
      diameters. A linear pH gradient is established only in two-step CIEF methodology
      using 3-10 pH 2.5% (v/v) carrier ampholyte. Hemoglobin A(0) and S variants are
      successfully resolved on DODAB/POE 40 stearate sequentially coated capillaries.

PMID- 22858000
TI  - Enterocytozoon bieneusi in Bovine Viral Diarrhea Virus (BVDV) infected and
      noninfected cattle herds.
AB  - Enterocytozoon bieneusi known as a causative agent of opportunistic infections
      instigating diarrhoea in AIDS patients was identified also in a number of
      immunocompetent patients and in a wide range of animals, including cattle. In the
      present study we tested if the Bovine Viral Diarrhea Virus (BVDV), the most
      common pathogen underlying immunosuppressive Bovine Viral Diarrhoea (BVD), can
      enhance the occurrence of opportunistic infections with E. bieneusi in cattle.
      Six dairy farms were investigated using ELISA to detect antibodies against or
      antigens arising from BVDV in collected sera. A total of 240 individual faecal
      samples from four age groups were examined for the presence of E. bieneusi by
      nested PCR. Sequence analysis of six E. bieneusi positive samples revealed the
      presence of the genotype I of E. bieneusi, previously described in cattle. The
      hypothesis expecting higher prevalence of E. bieneusi in BVDV positive cattle
      herds was not confirmed in this study; however this is the first description
      about E. bieneusi in cattle in the Czech Republic.

PMID- 22858001
TI  - Evaluation of a microsphere-based immunofluorescence assay for the determination
      of Immunoglobulin A concentrations in cerebrospinal fluid of dogs.
AB  - The simultaneous increase of immunoglobulin A (IgA) in serum and cerebrospinal
      fluid (CSF) is a characteristic finding in dogs suffering from canine steroid
      responsive meningitis-arteritis (SRMA). The study aimed at developing and
      evaluating a microsphere-based immunofluorescence assay (MIA) for the measurement
      of IgA, trying to fulfill the need of a quicker method using only small volumes
      of CSF. Microsphere beads were coated with goat-anti-dog IgA antibodies and bound
      IgA was detected by a mouse-anti-dog IgA antibody in combination with a PE
      labeled goat-anti-mouse IgG. CSF from 44 dogs were tested for IgA and compared
      with an in-house utilized ELISA. Using clinical relevant reference ranges, the
      new method showed a good agreement (84.17%) with the ELISA. A method comparison
      revealed a moderate agreement only. These findings indicate that the MIA will not
      replace the ELISA, but it opens the possibility for further research with
      microsphere-based assays.

PMID- 22858002
TI  - Intracellular trafficking mechanism, from intracellular uptake to extracellular
      efflux, for phospholipid/cholesterol liposomes.
AB  - Liposomes are widely used as drug delivery vehicles to transfer chemotherapeutic
      agents, proteins, and nucleic acids into target cells. To improve therapeutic
      effects and reduce unexpected toxic side-effects, it is necessary to understand
      the mechanism of liposomal uptake into cells, and the intracellular fate of
      internalized liposomes. The intracellular fate of synthesized components used in
      the construction of liposomes remains unclear. In the work presented here, we
      investigated the trafficking processes from intracellular uptake to extracellular
      efflux using conventional liposomes constructed with phospholipids (DOPC) and
      cholesterols (Chol). Following intracellular transport of liposomes via
      endocytosis, DOPC was localized in the endoplasmic reticulum (ER) and Golgi
      apparatus after escape from the endosome/lysosome, whereas Chol was only
      localized in the ER. Moreover, proteins involved in the intracellular trafficking
      of liposomal components were identified. Additionally, we showed that DOPC was
      partly effluxed via ABCG1, while Chol was partly effluxed via ABCA1 or ABCB1;
      suggesting that each liposomal component examined in this study was effluxed
      through different transporters. Our findings offer valuable information regarding
      targeted delivery to specific intracellular organelles, and how to possibly avoid
      unexpected toxic effects following multiple applications of liposome
      formulations.

PMID- 22858003
TI  - Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through
      knockdown of cofilin-1 by carbon nanohorn delivered siRNA.
AB  - We synthesized a non-viral delivery system (f-CNH3) for small interfering RNA
      (siRNA) by anchoring a fourth-generation polyamidoamine dendrimer (G4-PAMAM) to
      carbon nanohorns (CNHs). Using this new compound, we delivered a specific siRNA
      designed to knockdown cofilin-1, a key protein in the regulation of cellular
      cytoskeleton, to human prostate cancer (PCa) cells. The carbon nanohorn (CNH)
      derivative was able to bind siRNA and release it in the presence of an excess of
      the polyanion heparin. Moreover, this hybrid nanomaterial protected the siRNA
      from RNAse-mediated degradation. Synthetic siRNA delivered to PCa cells by f-CNH3
      decreased the cofilin-1 mRNA and protein levels to about 20% of control values.
      Docetaxel, the drug of choice for the treatment of PCa, produced a concentration
      dependent activation of caspase-3, an increase in cell death assessed by lactate
      dehydrogenase release to the culture medium, cell cycle arrest and inhibition of
      tumor cell proliferation. All of these toxic effects were potentiated when
      cofilin-1 was down regulated in these cells by a siRNA delivered by the
      nanoparticle. This suggests that knocking down certain proteins involved in
      cancer cell survival and/or proliferation may potentiate the cytotoxic actions of
      anticancer drugs and it might be a new therapeutic approach to treat tumors.

PMID- 22858004
TI  - The induction of angiogenesis by cerium oxide nanoparticles through the
      modulation of oxygen in intracellular environments.
AB  - Angiogenesis is the formation of new blood vessels from existing blood vessels
      and is critical for many physiological and pathophysiological processes. In this
      study we have shown the unique property of cerium oxide nanoparticles (CNPs) to
      induce angiogenesis, observed using both in vitro and in vivo model systems. In
      particular, CNPs trigger angiogenesis by modulating the intracellular oxygen
      environment and stabilizing hypoxia inducing factor 1alpha endogenously.
      Furthermore, correlations between angiogenesis induction and CNPs physicochemical
      properties including: surface Ce(3+)/Ce(4+) ratio, surface charge, size, and
      shape were also explored. High surface area and increased Ce(3+)/Ce(4+) ratio
      make CNPs more catalytically active towards regulating intracellular oxygen,
      which in turn led to more robust induction of angiogenesis. Atomistic simulation
      was also used, in partnership with in vitro and in vivo experimentation, to
      reveal that the surface reactivity of CNPs and facile oxygen transport promotes
      pro-angiogenesis.

PMID- 22858005
TI  - Liposomal amphotericin B in comparison to sodium stibogluconate for Leishmania
      braziliensis cutaneous leishmaniasis in travelers.
AB  - BACKGROUND: New World cutaneous leishmaniasis is mostly acquired in the Amazon
      Basin of Bolivia where L viannia (V) braziliensis is endemic. Treatment with
      systemic pentavalent antimonial compounds has been shown to be effective in
      achieving clinical cure in only 75% of cases. OBJECTIVE: We sought to assess the
      efficacy and safety of liposomal amphotericin B (L-AmB) treatment for primary
      infection of cutaneous L (V) braziliensis. METHODS: A prospective observational
      evaluation was performed for cutaneous leishmaniasis due to L (V) braziliensis
      which was treated with L-AmB, 3 mg/kg, for 5 consecutive days, and a sixth dose
      on day 10. This therapy regimen was compared with the treatment regimen of sodium
      stibogluconate (SSG) 20 mg/kg for 3 weeks. RESULTS: Our study was divided into
      two groups; 34 patients received L-AmB and 34 received SSG treatment. Almost all
      patients were infected in Bolivia. In the L-AmB group, 29 patients (85%) had
      complete cure compared with 70% in the SSG group (P = not significant), 4 other
      patients were slow healers, and only one patient needed additional treatment with
      SSG. No relapses were seen during a mean 29-month follow-up period. Failure rate
      was 3% in the L-AmB versus 29% in the SSG group (P = .006). Treatment was
      interrupted in 65% of patients taking SSG because of adverse events, whereas all
      patients receiving L-AmB completed treatment. LIMITATIONS: This was a non-blinded
      comparative study. CONCLUSIONS: Comparison of L-Amb to SSG treatment for L (V)
      braziliensis shows that the former is effective, better tolerated, and more cost
      effective. L-AmB should therefore be considered as the first-line treatment
      option for cutaneous L (V) braziliensis infection.

PMID- 22858006
TI  - Common features of diverse circuits.

PMID- 22858007
TI  - Monte Carlo simulation of COMS ophthalmic applicators loaded with Bebig I25.S16
      seeds and comparison with planning system predictions.
AB  - PURPOSE: To simulate the Bebig model I125.S16 source and obtain AAPM Task Group
      Report 43 brachytherapy dosimetry parameters for comparison to consensus and
      previously published values. The seed model will then be incorporated into a
      Monte Carlo model of COMS eye plaques and simulation results will be used for
      seed-carrier set modeling in a commercial planning system. METHODS: PENELOPE was
      used to simulate the seed and the applicators for different sizes and loading
      levels. The corresponding TG-43U1 dosimetric parameters of the seed were
      calculated. Bebig Plaque Simulator was used. RESULTS: The air kerma strength, the
      dose rate constant and the radial dose and 2D anisotropy functions found showed a
      good agreement with those published by other authors. Dose distributions were
      determined for the 12 and 20 mm COMS plaques loaded with a single seed and for
      the 12 mm plaque fully loaded. The plaque effect on the eye dose and the
      interseed absorption were evaluated. If the plaque is loaded with a single seed,
      the dose in the central axis reduces about 10% at 5-6 mm depth with respect to
      the case in which the plaque is not present. This reduction does not depend on
      the plaque size. When the plaque is fully loaded, an additional reduction in the
      dose with respect to the dose in water is observed mainly due to the effect of
      the Silastic carrier. The mean dose reduction in the central axis of the 12 mm
      plaque due to the interseed absorption was 0.5%. A new physics file for the
      planning system was created with the results obtained from the simulations.
      Results obtained using this adapted model for the 12 mm plaque fully loaded
      agreed with the corresponding simulation. Dose rate at the prescription point
      differs 4.7% when the adapted model is used instead of the default model.
      CONCLUSIONS: Simulation results for COMS plaques are consistent with those
      published for other seeds. The planning system studied appears as a good tool for
      dose calculation in ophthalmic brachytherapy treatments. The new physics model,
      built up from Monte Carlo results, has been commissioned by comparing
      calculations made with the planning system to those obtained from Monte Carlo
      simulations.

PMID- 22858008
TI  - Obesity-related differences in muscular capacity during sustained isometric
      exertions.
AB  - Over one-third of the world adult population is overweight or obese, and the
      prevalence continues to increase. Obesity is a risk factor for injury, and the
      growing prevalence may be associated with increases in the future incidence and
      cost of injuries. In this study, we examined obesity-related differences in
      muscular capacity during sustained isometric exertions involving hand grip,
      shoulder flexion, and trunk extension. Thirty-six young individuals who were
      obese or not obese (aged 18-29) completed these exertions at fixed levels of
      absolute loads involving low-moderate levels of effort. Individuals who were
      obese had an overall ~20% higher absolute strength, but ~20% lower relative
      strength. These differences were most evident in the hand grip and shoulder
      exertions. Parameters of fitted exponential relationships between endurance time
      and task demands (as a percentage of strength) were similar in both groups.
      Perceptual and performance responses were also consistent between groups.
      Accordingly, we conclude that obesity may not substantially influence muscular
      capacity for these tasks.

PMID- 22858009
TI  - Transient effects of harsh luminous conditions on the visual performance of
      aviators in a civil aircraft cockpit.
AB  - The aim of this work was to examine how harsh luminous conditions in a cockpit,
      such as lightning in a thunderstorm or direct sunlight immediately after an
      aircraft passes through clouds, may affect the visual performance of pilots, and
      how to improve it. Such lighting conditions can result in the temporary visual
      impairment of aviators, which may greatly increase the risk of accidents. Tests
      were carried out in a full-scale simulator cockpit in which two kinds of dynamic
      lighting scenes, namely pulse changed and step changed lighting, were used to
      represent harsh luminous conditions. Visual acuity (VA), reaction time (RT) and
      identification accuracy (IA) were recorded as dependent variables. Data analysis
      results indicate that standardized VA values decreased significantly in both
      pulsing and step conditions in comparison with the dark condition. Standardized
      RT values increased significantly in the step condition; on the contrary, less
      reaction time was observed in the pulsing condition. Such effects could be
      reduced by an ambient illumination provided by a fluorescent lamp in both
      conditions. The results are to be used as a principle for optimizing lighting
      design with a thunderstorm light.

PMID- 22858010
TI  - Molecular identification of green algae from the rafts based infrastructure of
      Porphyra yezoensis.
AB  - To provide more information on the origin of the Ulva prolifera bloom in Qingdao
      sea area in China from 2007 to 2011, the diversity of green algae growing on the
      rafts of Porphyra yezoensis on the coast in Jiangsu Province was investigated
      based on ITS, rbcL and 5S sequences. Eighty-four of green algal samples from
      various sites and cruises in 2010 and 2011 were collected. According to ITS and
      rbcL sequences, samples from the rafts of P. yezoensis fell into four clades:
      Ulva linza-procera-prolifera (LPP) complex, Ulva flexuosa, Blidingia sp. and
      Urospora spp. However, based on the 5S rDNA, a more resolved DNA marker, only one
      of the 84 samples belonged to U. prolifera. Combined with the previous reports,
      it is likely that U. prolifera bloom in Qingdao sea area might consist of more
      than one origin, and Porphyra cultivation rafts might be one of the causes.

PMID- 22858011
TI  - Particulate metal distribution in Tagus estuary (Portugal) during a flood
      episode.
AB  - Particulate metal concentrations were assessed before, during and after a flood
      episode in the Tagus estuary. Particulate metal concentrations showed a decrease
      during the flood period and very similar values in the months before and after
      the flood event. Before this period, sampling station characteristics were
      verified to be homogenous during the peak of the flooding event, as all of the
      sampling stations assumed very specific characteristics. One of the main
      consequences from the flood, concurrent with a decrease in particulate metal
      concentrations, was the high input of SPM into the estuarine area. This finding
      indicates higher levels of heavy metals in fine-sized particles at low SPM
      concentration than those present in coarser particles at high SPM levels. These
      periodic flood events can be considered as estuarine contamination masks and
      should be interpreted as periods of dilution in heavy metal contamination rather
      than as an estuarine cleansing process.

PMID- 22858012
TI  - Response by Dauvin to correspondence by Christophe Luczak and Nicolas Spilmont on
      'Are the Eastern and Western Basins of the English Channel two separate
      ecosystems? Get back in line with some cautionary comments'.

PMID- 22858013
TI  - Elevated levels of radium-226 and radium-228 in marine sediments of the Norwegian
      Trench ("Norskrenna") and Skagerrak.
AB  - Oil and gas extraction activities discharge waters bearing radium isotopes which
      may potentially be transported to locations distant from the discharge point.
      Sediment cores from the Norwegian Trench and Skagerrak, potential sinks for North
      Sea discharges, were analyzed for the contents of these isotopes. All cores were
      such that data could be obtained from periods prior to and during extensive
      operations in the North Sea. Results indicate elevated levels of radium isotopes
      in upper sedimentary layers when compared to data for the Baltic Sea and
      Kattegat. Although diagenetic processes involving manganese cycling may be
      responsible for these enrichments, the data support previous work indicating a
      possible influence of North Sea discharges on sediments of the area. The results
      highlight the need for further work on elaborating background levels of these
      isotopes in the North Sea and related areas such that possible impacts of these
      discharges can be properly evaluated.

PMID- 22858014
TI  - Biomarkers responses in muscle of Senegal sole (Solea senegalensis) from a heavy
      metals and PAHs polluted estuary.
AB  - The biochemical responses in muscle, such as the enzymatic activities of
      acetylcholinesterase, lactate dehydrogenase and isocitrate dehydrogenase, were
      studied in sole (Solea senegalensis) collected in Huelva estuary (SW Spain), in
      the vicinity of a petrochemical and mining industry. The sampling sites showed
      different type and degree of pollution. The results demonstrated significant
      differences in muscle activities of AChE and IDH in Odiel and Tinto Rivers
      compared to control fish. LDH activity did not show any difference between
      sampling sites. Significant correlations were established between some biomarkers
      and heavy metals: AChE was correlated with Pb, Cd and Cu concentrations in water;
      IDH activity was correlated with Cd and Cu concentrations in water and As, Pb and
      Cd concentrations in sediments; LDH activity was correlated with As and Zn
      concentration in water and Cd concentration in sediment. Only one correlation was
      established between the biomarkers analysed and the concentrations of PAHs:
      benzo(b)fluoranthene concentration in sediment and IDH.

PMID- 22858015
TI  - Non-invasive monitoring of male and female numbat (Myrmecobius fasciatus:
      Myrmecobiidae) reproductive activity.
AB  - The reproductive endocrinology of the highly endangered numbat (Myrmecobius
      fasciatus) is described for the first time. Patterns of faecal steroid secretion
      (progesterone [PM], oestradiol-17beta [E2] and testosterone [TM] metabolites)
      were examined within a captive numbat population over 1 year and revealed a
      highly synchronized seasonal pattern of reproduction. TM secretion increased
      progressively from September to November, peaked in December and then decreased
      in February. All females displayed luteal phases (1-3), between late-November to
      late-March, in association with pregnant (Pr, n=4), non-productive mated oestrous
      cycles (NMEC, n=8) and non-mated oestrous cycles (NEC, n=6). The mean oestrous
      cycle length was 30.2 +/- 1.1 d (n=11) and was comprised of a mean follicular
      (n=11) and luteal (n=18) phase length of 16.2 +/- 1.6 d and 14.0 +/- 0.8 d,
      respectively. No variation in mean luteal phase length or PM concentration
      according to cycle type (Pr, NMEC, NEC) or cycle number (1st, 2nd or 3rd cycle)
      was detected. Longitudinal profiling of PM secretion confirmed that the female
      numbat is seasonally polyoestrous and that the luteal phase occurs spontaneously.
      Changes in the secretion of E2 provided little instructive information on
      oestrous cycle activity. Mating success was 31%, with age and subject having no
      effect on mating success. Timing of introduction, of male to female, appeared to
      impact mating success, with paired animals introduced for a shorter time frame
      (<=14 d) prior to the first observed mating successfully producing young.
      Collectively, results of the present study confirm that PM and TM can be reliably
      used to index numbat reproductive activity.

PMID- 22858016
TI  - Factors influencing attractiveness of soft tissue profile.
AB  - BACKGROUND AND AIM: The factors affecting the attractiveness of the soft tissue
      profile are assessed in only very few nonmatched and controversial studies. We
      aimed to evaluate these factors in a matched comprehensive study. METHODS:
      Profile photographs of 100 students with good occlusion were sorted according to
      facial beauty by 20 judges. After excluding 40 unmatched subjects or those with
      marginal scores, 12 soft tissue variables were compared among profiles of 30
      attractive and 30 unattractive matched participants (t test, alpha = 0.05).
      RESULTS AND CONCLUSION: As the most important factor, excessive mandibular
      retrusion made both men and women unattractive. Both attractive men and women
      tended to have less prominent noses with higher nose tips, protruded upper lips
      compared with the position of lower lips, and deeper lower faces. Closeness of
      lips to the middle of vertical chin-nose distance enhanced female beauty only.
      Straight profiles and more protruded maxillae merely made men more attractive.

PMID- 22858017
TI  - Implantation of radioactive particles into the cranial base and orbital apex with
      the use of a magnetic resonance imaging-based surgical navigation system.
AB  - OBJECTIVE: The aim of this study was try to find a new way with high precision to
      implant (125)I-radioactive particles for safe and effective control of tumors
      that have invaded into the cranial base and orbital regions. STUDY DESIGN: Eight
      patients with invasive adenoid cystic carcinoma of the cranial base and orbital
      apex and a history of multiple surgeries were selected. A preoperative magnetic
      resonance scan was performed and the Brainlab surgical navigation system was used
      to aid the surgery. RESULTS: The radioactive particles were distributed evenly
      within the tissue and accurately positioned. No intracranial injury or visual
      impairment occurred, and the treatment was effective. CONCLUSIONS: The
      implantation of radioactive particles with the use of magnetic resonance imaging
      guidance is an effective and safe method for treating invasive malignancies of
      the skull base and orbital apex, and it should be considered for conditional use.

PMID- 22858018
TI  - Case presentation of florid cemento-osseous dysplasia with concomitant cemento
      ossifying fibroma discovered during implant explantation.
AB  - A 39-year-old African American woman presented for treatment of a symptomatic
      mandibular right first molar with a large, periapical radiolucency. After initial
      attempts at endodontic therapy, this tooth was ultimately extracted owing to
      unabated symptoms. The extraction site underwent ridge preservation grafting,
      implant placement, and restoration. After 26 months of implant function, the
      patient returned with clinical symptoms of pain, buccal swelling, and the
      sensation of a "loose" implant. This case report details a diagnosis of 2
      distinct disease entities associated with the implant site, a cemento-ossifying
      fibroma and florid cemento-osseous dysplasia of the mandible. This diagnosis was
      determined from clinical, surgical, radiographic, and histopathologic evidence
      after biopsy and removal of the previously osseointegrated implant following
      postinsertion failure by fibrous encapsulation. Before implant therapy, it is
      essential to conduct a thorough radiographic evaluation of any dental arch with
      suspected bony lesions to prevent implant failure.

PMID- 22858019
TI  - Long-term dental and skeletal changes in patients submitted to surgically
      assisted rapid maxillary expansion: a meta-analysis.
AB  - OBJECTIVE: This meta-analysis evaluated long-term dental and skeletal changes in
      patients submitted to surgically assisted rapid maxillary expansion. METHODS: A
      search was performed in electronic databases. Human clinical trials with patients
      submitted to surgically assisted rapid maxillary expansion with a follow-up of at
      least 1 year after expansion were selected. A methodological quality scoring
      process was used. A meta-analysis was performed to compare measurements of
      skeletal and dental structures. RESULTS: Three hundred sixty-five titles and
      abstracts were read. Ultimately 10 studies met the inclusion criteria. The 3
      articles ranked as presenting low methodological quality were excluded. Three
      measurements could be compared and 3 time periods were used to assess changes.
      CONCLUSIONS: There is moderate evidence to conclude that maxillary alveolar width
      and intercanine and intermolar width have a long-term significant increase as a
      result of surgically assisted rapid maxillary expansion. A significant relapse is
      expected in the intercanine width after expansion.

PMID- 22858020
TI  - Facial trauma patients with a preexisting psychiatric illness: a 5-year study.
AB  - OBJECTIVES: The aim of this study was to identify and assess the demographics and
      presence of preexisting psychiatric disorders in an adult patient cohort admitted
      for the management of a facial injury. STUDY DESIGN: The analysis included
      demographics, type of facial injury, length of hospital stay, and psychiatric
      diagnosis according to criteria as set out in the DSM-IV-TR-2000. RESULTS: We
      identified 71 patients who had confirmed psychiatric comorbidity. A range of
      intentional, unintentional, and recidivist injuries were identified. We found a
      significant association between length of hospital stay and the number of
      diagnostic categories of preexisting psychopathology (P < .05). CONCLUSIONS: This
      study further confirms that there is a subgroup of facially injured patients with
      preexisting psychiatric illness which often goes unrecognized and untreated.
      Early recognition, together with appropriate referral to and management by
      liaison psychiatry may play an important role in reducing the rate of facial
      trauma recidivism.

PMID- 22858021
TI  - Results of oral implant-supported prostheses after mandibular vertical alveolar
      ridge distraction: a propos of 54 sites.
AB  - OBJECTIVE: The aim of this study was to present retrospective long-term results
      of oral implant-supported prostheses after mandibular vertical alveolar ridge
      distraction. STUDY DESIGN: Patients who had alveolar mandibular distraction
      before oral rehabilitation from 1999 to 2009 were retrospectively reviewed.
      RESULTS: Fifty-four distractions were performed in 25 women and 12 men with a
      mean age of 51.7 years. Seventeen patients had bilateral distraction. Most of the
      distracted sites were posterior. Global major complications were major
      misdirection (3.7%), fracture (3.7%), and permanent alveolar nerve paresthesia (1
      patient). All of the patients experienced osseous improvement. Mean height of the
      distraction was 11.7 mm. A total of 127 implants were inserted with survival and
      success rates, respectively, of 100% and 96.2% (mean follow-up of 62 months). All
      of the patients had satisfactory oral rehabilitation. CONCLUSIONS: Mandibular
      alveolar vertical distraction could be a reliable and effective procedure with
      precise indications. A less complicated implant distractor may simplify the
      procedure.

PMID- 22858022
TI  - Mandibular coronoid process grafting for alveolar ridge defects.
AB  - OBJECTIVE: We describe the clinical results of mandibular augmentation with
      coronoid process bone grafts for dental implant insertion. STUDY DESIGN: Fifteen
      patients with vertical and transverse defects of the posterior alveolar process
      of the mandible were treated. All patients underwent mandibular rehabilitation
      with autogenous coronoid process bone grafts via minimal-access surgery. After 6
      months, 40 dental implants were inserted. RESULTS: At the time of implant
      insertion, the grafted alveolar ridges showed mean transverse and vertical
      augmentations of 3.07 and 2.80 mm, respectively. At 24 months after implant
      surgery, the cumulative implant survival rate was 95% and mean marginal bone loss
      was 1.6 +/- 0.18 mm. No complete bone graft loss or infection occurred.
      CONCLUSIONS: Coronoid process bone grafts can be used to reconstruct moderate
      defects in edentulous alveolar processes. The insertion of the graft with minimal
      access in a tunneled fashion minimizes the risk of infection.

PMID- 22858023
TI  - MicroRNA-155 inhibits proliferation and migration of human extravillous
      trophoblast derived HTR-8/SVneo cells via down-regulating cyclin D1.
AB  - MiR-155 is known to participate in various cellular processes by targeting gene
      expression. We previously revealed a link between miR-155 and perturbation of
      trophoblast invasion and differentiation. This study aimed to investigate the
      target molecule(s) of miR-155 on the influence on the proliferation and migration
      of trophoblast cells. Bioinformatics analysis showed that, at the 3' untranslated
      region (UTR) of cyclin D1, six bases are complementary to the seed region of miR
      155. Luciferase assays and cyclin D1 3'UTR transfection assays validated that
      cyclin D1 3'UTR was the target of miR-155 in HTR-8/SVneo cells. Overexpression of
      miR-155 in HTR-8/SVneo cells reduced the level of cyclin D1 protein, decreased
      cell proliferation and invasion, and increased cell number at the G1 stage.
      Furthermore, the increased expression of miR-155 also regulated the protein
      levels of kinase inhibitory protein p27 and phosphorylated cytoskeletal protein
      filamin A. In conclusion, we found that cyclin D1 may be a target of miR-155 in
      HTR-8/SVneo cells, and demonstrated a negative regulatory role of miR-155
      involved in cyclin D1/p27 pathway in proliferation and migration of the cells.

PMID- 22858024
TI  - Endophthalmitis is not a "never event".

PMID- 22858025
TI  - Corneal disease in China.

PMID- 22858026
TI  - Autofluorescence in posterior uveitis.

PMID- 22858027
TI  - T-cell leukemia.

PMID- 22858028
TI  - Human corneal endothelium regeneration.

PMID- 22858029
TI  - Scleritis and episcleritis.

PMID- 22858030
TI  - Pupil size and LASIK.

PMID- 22858033
TI  - Pediatric IOL opacification.

PMID- 22858034
TI  - Atropine dose to treat myopia.

PMID- 22858036
TI  - Methicillin-resistant Staphylococus aureus.

PMID- 22858038
TI  - Intra-arterial chemotherapy for retinoblastoma.

PMID- 22858040
TI  - [Medical English as a foreign language - there can be no more excuses!].

PMID- 22858041
TI  - The economic benefits of cell salvage in obstetric haemorrhage.
AB  - BACKGROUND: Cell salvage is increasingly used in the management of major
      obstetric haemorrhage. Its financial considerations were evaluated over a 5-year
      period. METHOD: Cell salvage was introduced in the Liverpool Women's NHS
      Foundation Trust in 2006. Data were collected from all cases in which it was set
      up and included the volume of blood processed and returned and whether surgery
      was elective or emergency. RESULTS: Between 1st January 2006 and 30th June 2011,
      cell salvage for collection was set-up 587 times and blood was returned in 137
      patients. Total volume of blood returned was 47143mL, equivalent to 189 units of
      packed red cells. The return rate was higher for emergency than elective cases
      (P=0.03). As the use of cell salvage has extended over time to include a greater
      proportion of patients, return rates have decreased (P<0.0001). The volume of
      blood returned from cell salvage was significantly related to the estimated blood
      loss (P<0.00001), with a best fit line described by estimated blood
      loss=3.45x+454, where x was the volume of blood returned. In 2011 total costs of
      cell salvage were L9245 for the equivalent of 83 units of blood. At the current
      price of L125 per unit of allogeneic blood this would have cost L10375: a saving
      of L1130. No intraoperative or postoperative complications associated with cell
      salvage were seen. CONCLUSION: The routine use of cell salvage was associated
      with more salvaged blood being returned to patients, which offset the cost of
      collection sets when compared to the cost of using allogeneic blood. Cell salvage
      is an appropriate expenditure to reduce the use of allogeneic blood.

PMID- 22858042
TI  - Management of HSV-1 encephalitis due to reactivation of HSV-1 during late
      pregnancy.
AB  - A previously healthy 31-year-old G4P2 woman at 33 weeks of gestation was admitted
      as an emergency with a pyrexia of 39 degrees C, vomiting, headache and neck
      stiffness associated with photophobia, phonophobia and visual and auditory
      symptoms. There were no heraldic signs of eclampsia. Polymerase chain reaction
      and testing for herpes simplex virus in the cerebrospinal fluid diagnosed herpes
      simplex-1 meningoencephalitis. Following acyclovir, the clinical course improved.
      Spontaneous vaginal delivery occurred at 39 weeks of gestation with epidural
      analgesia using ropivacaine. Mother and child were neurologically normal and
      healthy 15 months later. Early administration of acyclovir is essential to reduce
      the risk of neurological complications. After treatment and a negative polymerase
      chain reaction for herpes simplex virus in the cerebrospinal fluid, epidural
      analgesia with local anesthetic and sufentanil is possible.

PMID- 22858043
TI  - Maternal critical care in the United Kingdom: developing the service.

PMID- 22858044
TI  - A comparison of epidural magnesium and/or morphine with bupivacaine for
      postoperative analgesia after cesarean section.
AB  - BACKGROUND: Magnesium can potentiate the antinociceptive effect of morphine. This
      prospective randomized double-blinded study was undertaken to establish the
      analgesic effect of adding magnesium to epidural morphine during cesarean
      section. METHODS: Two hundred patients undergoing cesarean section under combined
      spinal-epidural anesthesia were recruited. After administration of intrathecal
      bupivacaine 10mg, patients were randomly assigned to receive one of four epidural
      study solutions: 0.1% bupivacaine 10 mL (Group B); 0.1% bupivacaine 10 mL and
      morphine 1.5mg (Group B+Mor); 0.1% bupivacaine 10 mL and magnesium 500 mg (Group
      B+Mg); or 0.1% bupivacaine 10 mL morphine 1.5mg and magnesium 500 mg (Group
      B+Mor+Mg). The primary outcome was the area under the curve for visual analog
      scale pain scores during 36 h postoperatively. Secondary outcomes included time
      to the use of rescue analgesics, patient satisfaction and side effects. RESULTS:
      Patients in Group B+Mor+Mg had lower for pain scores and area under the curve
      pain scores both at rest and on movement, increased time for first analgesic
      request, and increased satisfaction score at 24h after surgery. CONCLUSION:
      Addition of magnesium 500 mg and morphine 1.5mg to epidural 0.1% bupivacaine 10
      mL reduced postoperative pain compared with addition of morphine or magnesium
      alone or no additive.

PMID- 22858045
TI  - Reduction in spinal-induced hypotension with ondansetron.

PMID- 22858046
TI  - Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic
      carboxymethyl-hexanoyl chitosan hydrogel.
AB  - Induced pluripotent stem cells (iPSCs) have promising potential in regenerative
      medicine, but whether iPSCs can promote corneal reconstruction remains
      undetermined. In this study, we successfully reprogrammed human corneal
      keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were
      cultured onto a serum- and feeder-free system in which they remained stable
      through 30 passages and showed ESC-like pluripotent property. To investigate the
      availability of iPSCs as bioengineered substitutes in corneal repair, we
      developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan
      (CHC) nanoscale hydrogel and found that such gel increased the viability and
      CD44+proportion of iPSCs, and maintained their stem-cell like gene expression, in
      the presence of culture media. Combined treatment of iPSC with CHC hydrogel
      (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured
      corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced
      corneal reconstruction by downregulating oxidative stress and recruiting
      endogenous epithelial cells to restore corneal epithelial thickness. Therefore,
      we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined
      with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance
      corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical
      residues may serve as an alternative cell source for personalized therapies for
      human corneal damage.

PMID- 22858047
TI  - Charge reversal of moisturous porous silica colloids by take-up of protons.
AB  - The net charge of porous Stober silica colloids is studied using a modified
      Poisson-Boltzmann theory in a spherical cell, with a focus on the case of water
      filled porous silica particles suspended in a non-aqueous solvent. We show that
      the silica's usual negative surface charge, due to deprotonisation of the Si-OH
      group, is counteracted by an excess uptake of protons in the water-filled pores
      of the particle at low enough pH. A small volume fraction of pores suffices to
      induce a point of zero charge at pH~4. Based on the difference in Donnan
      potential between the porous medium and the solvent a relation can be constructed
      that describes the location of the point of zero charge analytically. The
      accuracy of this relation is confirmed by numerical calculations. For Stober
      silica in water we find a charge reversal below pH~3, which is in this case
      solely a result of the selective uptake of cations in the porous network.

PMID- 22858048
TI  - Heterostructured Tin oxide-pillared tetratitanate with enhanced photocatalytic
      activity.
AB  - An effective active heterostructured photocatalyst of porous SnO(2)-pillared
      tetratitanate nanocomposite is synthesized by assembling tetratitanate nanosheets
      with SnO(2) nanoparticles via an exfoliation-restacking route. The nanocomposite
      was characterized by powder X-ray diffraction, high-resolution transmission
      electron microscope, thermogravimetric analysis, UV-vis DRS, X-ray photoelectron
      spectroscopy, and N(2) adsorption-desorption measurements. It was found that the
      pillared nanaocomposite is mesoporous with a gallery height of about 2 nm and a
      specific surface area of 154 m(2)/g. The pillared nanaocomposite exhibited
      enhanced photocatalytic activity in the photodegradation of Rhodamine B under UV
      light irradiation. The improved performance is attributed to the electronic
      coupling between the host and the guest components, as well as its high surface
      area and mesoporosity.

PMID- 22858050
TI  - Accounting for context in studies of health inequalities: a review and comparison
      of analytic approaches.
AB  - BACKGROUND: A common epidemiologic objective is to evaluate the contribution of
      residential context to individual-level disparities by race or socioeconomic
      position. PURPOSE: We reviewed analytic strategies to account for the total
      (observed and unobserved factors) contribution of environmental context to health
      inequalities, including conventional fixed effects (FE) and hybrid FE implemented
      within a random effects (RE) or a marginal model. METHODS: To illustrate results
      and limitations of the various analytic approaches of accounting for the total
      contextual component of health disparities, we used data on births nested within
      neighborhoods as an applied example of evaluating neighborhood confounding of
      racial disparities in gestational age at birth, including both a continuous and a
      binary outcome. RESULTS: Ordinary and RE models provided disparity estimates that
      can be substantially biased in the presence of neighborhood confounding. Both FE
      and hybrid FE models can account for cluster level confounding and provide
      disparity estimates unconfounded by neighborhood, with the latter having greater
      flexibility in allowing estimation of neighborhood-level effects and
      intercept/slope variability when implemented in a RE specification. CONCLUSIONS:
      Given the range of models that can be implemented in a hybrid approach and the
      frequent goal of accounting for contextual confounding, this approach should be
      used more often.

PMID- 22858049
TI  - Small size for gestational age and the risk for infant mortality in the
      subsequent pregnancy.
AB  - PURPOSE: To examine the association between small for gestational age (SGA) in
      the first pregnancy and risk for infant mortality in the second pregnancy.
      METHODS: This is a population-based, retrospective cohort study in which we used
      the Missouri maternally linked cohort dataset for 1978-2005. Analyses were
      restricted to women who had two singleton pregnancies during the study period.
      The exposure was SGA in the first pregnancy, whereas the primary outcome was
      infant mortality in the second pregnancy. Kaplan-Meier Estimate and Cox
      proportional hazard regression were conducted. RESULTS: Infant mortality was
      significantly greater among mothers with previous SGA (P < .01). A persistent
      association of previous SGA with subsequent infant mortality was observed
      (adjusted hazard ratio [AHR] 1.35, 95% confidence interval [95% CI] 1.24-1.48).
      Race-specific data illustrated that black women with a previous SGA birth were
      40% more likely to experience infant mortality (AHR 1.40, 95% CI 1.21-1.63) than
      their counterparts without a history of SGA, but white women with a previous SGA
      had an increased risk of 31% (AHR 1.31, 95% CI 1.17-1.46). CONCLUSIONS: Women
      with previous SGA bear increased risks for subsequent infant mortality, which was
      greater among black mothers. Hence, SGA plays an important role in the black
      white disparity in infant mortality. Women's previous childbearing experiences
      could serve as important criterion in determining appropriate interconception
      strategies to improve infant health and survival.

PMID- 22858051
TI  - [Isolated traumatic injuries of the axillary nerve. Radial nerve transfer in four
      cases and literatura review].
AB  - OBJECTIVE: To analyze the results of an initial series of four cases of traumatic
      injuries of the axillary nerve, treated by a nerve transfer from the triceps long
      branch of the radial nerve. An extensive analysis of the literature has also been
      made. MATERIALS AND METHODS: Four patients aged between 21 and 42 years old
      presenting an isolated traumatic palsy of the axillary nerve were operated
      between January 2007 and June 2010. All cases were treated by nerve transfer six
      to eight months after the trauma. The results of these cases are analyzed, the
      same as the axillary nerve injuries series presented in the literature from 1982.
      RESULTS: One year after the surgery, all patients improved their abduction a mean
      of 70 degrees  (range 30 to 120 degrees ), showing a M4 in the British Medical
      Council Scale. No patient complained of triceps weakness after the procedure.
      These results are similar to those published employing primary grafting for the
      axillary nerve. CONCLUSIONS: Isolated injuries of the axillary nerve should be
      treated with surgery when spontaneous recovery is not verified 6 months after the
      trauma. Primary repair with grafts is the most popular surgical technique, with a
      rate of success of approximately 90%. The preliminary results of a nerve transfer
      employing the long triceps branch are similar, and a definite comparison of both
      techniques with a bigger number of cases should be done in the future.

PMID- 22858052
TI  - [Perspectives of cell therapy in sequelae from cerebrovascular accidents].
AB  - INTRODUCTION: Spontaneous intracerebral hemorrhage (ICH) is associated with
      mortality between 40 and 50% of cases. Among the survivors, only 10% are
      independent after one month, there is no effective treatment of sequelae, except
      for the limited possibilities providing for rehabilitation. OBJECTIVES: We review
      the current experience with intracerebral transplantation of mesenchymal stem
      cells (MSCs) obtained from bone marrow as a potential treatment of neurological
      sequelae occurring after experimental ICH. MATERIAL AND METHODS: We describe the
      model of ICH by intracerebral administration of collagenaseIV at basal ganglia
      level in Wistar rats. Neurological deficits caused by ICH can be quantified
      through a variety of functional assessment test (NMSS, Rota-rod, VTB-test).
      5*10allogeneic MSCs in 10MUl of saline were administered intracerebrally in 10
      animals, 2 months after ICH. In another 10 animals (controls) the same volume of
      saline was administered. Changes in the functional deficits were assessed during
      the next 6 months in both experimental groups. RESULTS: The results suggested
      therapeutic efficacy of MSCs transplantation and showed that transplanted stem
      cells can survive in the injured brain, transforming into neurons and glial
      cells. This form of cell therapy induces reactivation of endogenous neurogenesis
      at the subventricular zone (SVZ) and achieves antiapoptotic protective effect in
      the injured brain. CONCLUSIONS: Cell therapy represents an important field of
      research with potential clinical application to treatment of neurological
      sequels, currently considered irreversible. Neurosurgeons should become involved
      in the development of these new techniques that are likely to shape the future of
      this specialty.

PMID- 22858053
TI  - Multicentric glioblastoma multiforme. Report of 3 cases, clinical and
      pathological study and literature review.
AB  - Multicentric gliomas are uncommon lesions of the central nervous system. Their
      management remains controversial, but histopathologic diagnosis after complete or
      partial resection must be performed to differentiate these tumors from other
      multiple cerebral lesions. Three cases of multicentric glioma are presented, one
      of which had supra- and infratentorial lesions. Histological specimens were
      obtained from removal of at least one of the lesions. Neuropathological
      examinations confirmed the diagnosis of grade IV malignant glioma (glioblastoma).
      All 3 patients died soon after symptom onset. However, one patient, with
      metachronous glioblastomas, had a comparatively long survival. We discuss the
      pathogenetic hypotheses and the diagnostic problems, especially the differential
      diagnosis from other multifocal diseases of the central nervous system.

PMID- 22858054
TI  - [Extended endoscopic endonasal approach to skull base].
AB  - OBJECTIVE: Different approaches to the skull base have been developed through the
      sphenoidal sinus. Traditional boundaries of the trans-sphenoidal approach can be
      extended in antero-posterior and lateral plane. We review our experience with
      extended endoscopic endonasal approach in 127 cases. METHODS: We used the
      extended endoscopic endonasal approach in 127 patients with different lesions of
      the skull base. This study specifically focuses on: type of lesions, surgical
      approach, outcome and surgical complications. RESULTS: Extended endoscopic
      endonasal approach was used in 127 patients with following lesions: 61 invasive
      adenomas to cavernous sinus, 10 clival chordomas, 21 craniopharyngiomas, 26
      meningiomas, 4 cerebrospinal fluid leakages, one meningoencephalocele, 2 malignan
      lesions and 2 thyroid ophthalmopathy. In tumoral lesions gross total resection
      was achieved in 82.5%, with better results in craniopharyngiomas 90.5%, followed
      by invasive adenomas with 85.2%, and meningiomas with 84.6%. The most frequent
      complications were the insipid (8.6%) diabetes, meningoencefalitis (3.9%) and the
      hydrocephalic (3.9%). Mortality was 3.9%. CONCLUSIONS: The extended endoscopic
      endonasal approach is a promising minimally invasive alternative for selective
      cases with skull base lesions. As techniques and technology advance this approach
      may become the procedure of choice for most lesions and should be considered an
      option in the management of the patients with these complex pathologies by skull
      base surgeon.

PMID- 22858055
TI  - Learning from Nature to design new biomolecules.

PMID- 22858057
TI  - The effect of loading in mechanical response predictions of bone lengthening.
AB  - Intramedullary (IM) distractor nails have become a viable alternative in bone
      distraction operations. Upon stabilization of the fractured/dissected limb via
      the nail, the resulting construct accommodates the load bearing function of the
      otherwise healthy limb. In establishing design performance targets for these
      devices, in vitro test conditions are widely accepted leaving the in vivo
      conditions aside. However, in vivo device failures due to distraction forces
      necessitate novel modeling considerations. It is especially important to simulate
      the loads in limb distraction, as this brings the bone-implant construct to a
      totally different regime than the hip-joint contact force (Point-Force Model,
      PFM). In this work we used a simplified approach to incorporate ligament
      stretching due to limb distraction via self-equilibrating spring elements in a
      finite-element setting (spring-force model, SFM). We compared the effect of
      loading type on load transmission paths through the locking pins, for these two
      distinct loading modes, namely, SFM and PFM. The two modes illustrate entirely
      different load transfer regimes around the bone/nail interface region. In order
      to avoid high contact stresses between the nail and the bone segments, it is
      advisable to keep the osteotomy away from the mid-range between the pin
      connections. It was also seen for both loading modes that including an additional
      pin at a load transfer location does not significantly alter the load carried by
      a single pin (the additional pin rather acts as a geometric stabilizer).

PMID- 22858056
TI  - Estrogens, hormone therapy, and hippocampal volume in postmenopausal women.
AB  - The brain atrophies in late life. However, there are many factors that either
      magnify or mitigate the rate of atrophy. Loss of estrogens during menopause and
      administration of hormone therapy have both been hypothesized as sources of
      individual variation in the prevalence of cortical and subcortical atrophy and
      loss of cognitive function in late adulthood. In this review we critically
      summarize and assess the extant rodent and human neuroimaging studies that
      examine the link between estrogens and hippocampal morphology and function and
      focus predominantly on human studies of the hippocampus in postmenopausal women.
      Several cross-sectional studies report that the size of the hippocampus is larger
      in women receiving hormone therapy while several other cross-sectional studies
      report either negligible effects or smaller volumes in women receiving hormone
      therapy. We suggest that these differences might be caused by the variation
      between studies in the age of the samples studied, the duration of therapy, and
      the age at which hormone therapy is initiated. Unfortunately, all of the human
      studies reviewed here are cross-sectional in nature. With the lack of well
      controlled randomized trials with neuroimaging measures on postmenopausal women
      both before and after some exposure interval, the effect of hormone therapy on
      hippocampal atrophy will remain equivocal and poorly understood.

PMID- 22858058
TI  - Hepatic iron deposition does not predict extrahepatic iron loading in mouse
      models of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis is characterized by tissue iron loading and associated
      organ damage. However, the phenotype can be highly variable. The relationship
      between iron loading of different organs and the temporal nature of its
      deposition is still not well understood. We examined the progression of tissue
      iron loading in three mouse models to advance our understanding of the natural
      history of iron deposition in hereditary hemochromatosis. Wild-type, Hfe(-/-),
      Tfr2(-/-), and Hfe(-/-)/Tfr2(-/-) mice were analyzed at 3, 5, 10, 26, and 52
      weeks, respectively. Hepatic, splenic, cardiac, and pancreatic iron
      concentrations were determined. Expression of both iron-regulatory and fibrosis
      genes was determined by quantitative real-time PCR in livers and hearts of 52
      week-old mice. In all models, hepatic iron increased rapidly, plateauing before
      10 weeks at different levels, depending on the genotype. Iron deposition in the
      pancreas and heart occurred after maximal iron loading of the liver was reached
      and was most marked in the Hfe(-/-)/Tfr2(-/-) mice. Although a significant
      positive correlation was identified between pancreatic and cardiac iron in all
      models at 52 weeks, there was no correlation between hepatic and either
      pancreatic or cardiac iron. There is variability in the timing and extent of
      tissue iron loading within a genotype, suggesting that hepatic iron levels in
      hereditary hemochromatosis may not accurately predict the iron content of other
      organs.

PMID- 22858059
TI  - Knockdown of osteopontin reduces the inflammatory response and subsequent size of
      postsurgical adhesions in a murine model.
AB  - Adhesions between organs after abdominal surgery remain a significant unresolved
      clinical problem, causing considerable postoperative morbidity. Osteopontin (OPN)
      is a cytokine up-regulated after cell injury and tissue repair. Our previous
      studies have shown that blocking OPN expression at sites of cutaneous wounding
      resulted in reduced granulation tissue and scarring. We hypothesize that it may
      be possible to similarly reduce inflammation-associated fibrosis that causes
      small-bowel adhesions after abdominal surgery. By using a mouse model, we deliver
      OPN antisense oligodeoxynucleotides via Pluronic gel to the surface of injured,
      juxtaposed small bowel and show a significant reduction of inflammatory cell
      influx to the developing adhesion and a dramatic reduction in the resulting
      adhesion size. A significant reduction in alpha-smooth muscle actin expression
      and collagen deposition within the mature adhesion is also demonstrated. We see
      no impact on mortality, and the healing of serosal injury to intact bowel
      appeared normal given the reduced inflammatory response. Our studies suggest that
      dampening OPN levels might be a potentially important target for anti-adhesion
      therapeutics.

PMID- 22858060
TI  - Simultaneous wavefront-guided photorefractive keratectomy and corneal collagen
      crosslinking after intrastromal corneal ring segment implantation for
      keratoconus.
AB  - PURPOSE: To study the results of simultaneous photorefractive keratectomy (PRK)
      and corneal collagen crosslinking (CXL) in keratoconus after previous
      intrastromal corneal ring segment (ICRS) implantation. SETTING: Enaim Laser
      Center, Jerusalem, Israel. DESIGN: Case series. METHODS: This study comprised
      patients with moderate keratoconus who had previous Intacs ICRS implantation with
      the Intralase laser at least 6 months before PRK-CXL. Wavefront-guided PRK and
      ultraviolet-A CXL were performed simultaneously. Refraction, uncorrected (UDVA)
      and corrected (CDVA) distance visual acuities, keratometry (K) values,
      endothelial cell count (ECC), pachymetry, corneal resistance factor (CRF), and
      corneal hysteresis (CH) were assessed 3, 6, and 12 months postoperatively.
      RESULTS: Twelve months after PRK-CXL, the mean decimal UDVA improved
      significantly from 0.20 +/- 0.12 (SD) to 0.55 +/- 0.15 (P<.01). The mean decimal
      CDVA improved from 0.58 +/- 0.13 to 0.77 +/- 0.17 (P=.01). The mean cylinder
      decreased from -3.60 +/- 1.70 to -1.30 +/- 1.10 diopters (D) (P<.001). The mean
      apex K decreased from 50.91 +/- 5.50 D to 46.61 +/- 4.52 D (P<.005). The other
      corneal parameters did not change significantly after treatment. No significant
      difference was found between the 6-month and 12-month results. No patient lost
      lines of CDVA. Mild haze remained in 11.1% of eyes 12 months after treatment.
      CONCLUSIONS: Simultaneous wavefront-guided PRK and CXL for keratoconus after ICRS
      implantation was safe and effective. It significantly improved the UDVA, CDVA,
      and central K value, and consequently the visual function, of patients with
      moderate keratoconus.

PMID- 22858061
TI  - Effect of primary posterior continuous curvilinear capsulorrhexis with posterior
      optic buttonholing on pilocarpine-induced IOL shift.
AB  - PURPOSE: To assess intraocular lens (IOL) shift along the visual axis induced by
      ciliary muscle contraction with pilocarpine after cataract surgery and to compare
      primary posterior continuous curvilinear capsulorrhexis (CCC) and posterior optic
      buttonholing with IOLs implanted in the bag. SETTING: Department of
      Ophthalmology, Medical University of Vienna, Vienna, Austria. DESIGN: Clinical
      trial. METHODS: Eyes with age-related cataract had cataract surgery with
      implantation of a nonaccommodating IOL (AF-1 YA-60BB). Surgery was performed with
      primary posterior CCC and posterior buttonholing in 1 eye (study eyes) and with
      conventional in-the-bag implantation in the contralateral eye (control eyes).
      After a minimum of 6 months postoperatively, the anterior chamber depth was
      assessed with partial coherence interferometry before and after application of
      pilocarpine 2.0% and, after a washout interval of 1 week, before and after the
      application of cyclopentolate 1.0%. RESULTS: Forty eyes of 20 patients were
      enrolled. A slight backward shift of the IOL (+78 MUm) in study eyes and in
      control eyes (+118 MUm) was detected after pilocarpine application (both P<.05).
      No significant difference in IOL shift was found between study eyes and control
      eyes (P=.19). CONCLUSIONS: Combined primary posterior CCC and posterior optic
      buttonholing did not affect IOL shift during pharmacologically stimulated ciliary
      muscle contraction compared with in-the-bag implanted IOLs. Capsule fibrosis
      diminished with primary posterior CCC but did not seem to be the only limiting
      factor in the accommodative IOL shift. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 22858062
TI  - Child maltreatment, subsequent non-suicidal self-injury and the mediating roles
      of dissociation, alexithymia and self-blame.
AB  - OBJECTIVE: Although child maltreatment is associated with later non-suicidal self
      injury (NSSI), the mechanism through which it might lead to NSSI is not well
      understood. The current retrospective case-control study examined associations
      between child maltreatment and later NSSI, and investigated the mediating roles
      of dissociation, alexithymia, and self-blame. METHODS: Participants were 11,423
      Australian adults (response rate 38.5%), randomly selected from the Australian
      Electronic White Pages, aged between 18 and 100 (M=52.11, SD=16.89), 62.2%
      female. Data were collected via telephone interviewing. Main outcome measures
      were reported history of child maltreatment (sexual abuse, physical abuse,
      neglect) and reported 12-month NSSI. Dissociation, alexithymia, and self-blame
      were examined as potential mediating variables in the relationship between child
      maltreatment and later NSSI. All analyses were conducted using logistic
      regression and adjusted for age and psychiatric diagnosis. RESULTS: Results
      differed by gender. Compared to no child maltreatment, physical abuse (OR 2.75,
      95% CI 1.68-4.51) and neglect (OR 2.56, 95% CI 1.65-3.99) independently increased
      the odds of NSSI among females. Physical abuse (OR 2.69, 95% CI 1.44-5.03)
      increased the odds of NSSI among males. Sexual abuse did not independently
      increase the odds of NSSI for males or females. For females, self-blame had the
      greatest effect on the child maltreatment-NSSI relationship (OR decreased by
      14.6%, p<.000), although dissociation and alexithymia also partially mediated the
      relationship. For males, dissociation had the greatest effect (OR decreased by
      12.9%, p=.003) with self-blame also having a relatively strong effect.
      CONCLUSIONS: The results indicate that child maltreatment, and in particular,
      physical abuse, is strongly associated with the development of subsequent NSSI
      and may be partially mediated by dissociation, alexithymia, and self-blame for
      females and dissociation and self-blame for males. Altering attributional style
      (through cognitive therapy or emotion focussed therapy) and improving the
      capacity to regulate emotions (through dialectical behaviour therapy) may
      contribute to reduction or cessation of NSSI.

PMID- 22858063
TI  - Reading between the lines: implicit assessment of the association of parental
      attributions and empathy with abuse risk.
AB  - OBJECTIVE: Researchers in the child maltreatment field have traditionally relied
      on explicit self-reports to study factors that may exacerbate physical child
      abuse risk. The current investigation evaluated an implicit analog task utilizing
      eye tracking technology to assess both parental attributions of child misbehavior
      and empathy. METHOD: Based on the observation that readers experience
      comprehension difficulty when encountering passages inconsistent with their
      beliefs, an eye tracker gauged the extent of difficulty parents experienced
      reading vignettes that inappropriately characterized a child as culpable for
      misbehavior and that presented a non-empathic child interaction. RESULTS: Results
      suggest self-reports of attributions and empathy are related to both child abuse
      potential and discipline intentions; however, the eye tracking analog for empathy
      correlated with abuse potential but not punishment decisions whereas the analog
      for attributions correlated with punishment decisions but not abuse potential.
      CONCLUSIONS: Such contrasts between self-report and analog assessment underscore
      the need for continued research studying theorized abuse risk constructs using
      alternative approaches to better identify the important risk markers associated
      with elevated child abuse risk and to minimize methodological overlap.

PMID- 22858064
TI  - Intellectual deficits in Brazilian victimized children and adolescents: a
      psychosocial problem?

PMID- 22858065
TI  - Caspase-7 in molar tooth development.
AB  - OBJECTIVES: The primary enamel knot (PEK) is a population of cells that shows
      spatio-temporal restricted apoptosis during tooth development. It has been shown
      that caspase-9 and Apaf-1 are essential for apoptosis in the PEK as well as the
      central caspase-3. Caspase-7, as another executioner member in the caspase
      machinery, is considered to have caspase-3 like properties. DESIGN: The aim of
      this study was to detect caspase-7 activation during molar tooth development with
      a special focus on the cells of the PEK and to correlate the expression with the
      pattern of apoptosis and caspase-3 activation. Apoptosis in the PEK was
      investigated in caspase-7 deficient mice to examine the functional consequence of
      loss of this specific caspase. In addition, odontoblasts and ameloblasts, which
      are known to undergo cell death during their secretory and maturation stages,
      were investigated. RESULTS: Cleaved caspase-7 was found in the apoptotic region
      of the PEK, however, caspase-7-deficient mice still possessed apoptotic cells in
      the PEK in a similar distribution to the wild type. Caspase-7 is therefore not
      essential for apoptosis in the PEK. Notably, cleaved caspase-7-positive cells
      were found at later stages in odontoblasts and ameloblasts, but expression did
      not correlate with apoptosis in these tissues. CONCLUSIONS: The results indicate
      a non-essential apoptotic role of caspase-7 in the PEK apoptosis but suggest also
      possible non-apoptotic functions for caspase-7 in tooth development.

PMID- 22858071
TI  - African-American parents' trust in their child's primary care provider.
AB  - OBJECTIVE: Patients' trust in their primary care providers has important
      implications in terms of health outcomes and, among minority patients, mitigating
      racial health disparities. This study aims to identify family, provider, and
      health care setting characteristics that predict African American parents' trust
      in their child's primary care provider and whether provider partnership-building
      communication style explains this association. METHODS: Data were collected via
      retrospective telephone interviews completed 2 weeks after a child's health care
      visit to 1 of 7 pediatric primary care clinics in Washington, DC (3 community
      health centers, 3 private practices, and 1 hospital-based clinic). Four hundred
      twenty-five self-identified African American parents of children 0 to 5 years of
      age participated. Parents completed several standard survey instruments about
      trust and provider communication style as well as demographic questionnaires
      about their family and their child's provider. RESULTS: A step-wise linear
      regression revealed significant independent effects of having a previous
      relationship with the provider and seeing a provider in a community health center
      (CHC) on higher trust. There was also evidence of mediation by provider
      communication style, suggesting that parents who take their child to a CHC report
      greater trust in their child's provider because they have higher perceptions of
      provider partnership building. CONCLUSIONS: African American parents' trust in
      their child's provider may be enhanced by continuity of care and greater use of a
      partnership-building communication style by providers.

PMID- 22858072
TI  - Lung transplant: an emerging challenge in the ICU.

PMID- 22858073
TI  - H(2)S--the newest gaseous messenger on the block.

PMID- 22858074
TI  - Effect of fixed-dose combined isosorbide dinitrate/hydralazine in elderly
      patients in the African-American heart failure trial.
AB  - BACKGROUND: Fixed-dose combined isosorbide dinitrate/hydralazine (FDC I/H)
      significantly improved outcomes in patients with advanced heart failure (HF)
      receiving background neurohormonal therapy in the African-American Heart Failure
      Trial (A-HeFT). In this analysis, we investigated treatment effects by age <65 or
      >=65 years. METHODS AND RESULTS: Time-to-event curves were produced by the Kaplan
      Meier method. Hazard ratios were calculated with the Cox proportional hazards
      model. Baseline characteristics showed that patients >=65 years old had less
      hypertensive and more ischemic HF, better quality of life (QoL) scores, higher
      plasma B-type natriuretic peptide and creatinine levels, and received less
      background neurohormonal therapy. Kaplan-Meier curves showed that FDC I/H
      improved mortality and event-free survival in elderly patients. The hazard ratios
      for mortality, first heart failure hospitalization, and event-free survival (both
      unadjusted and adjusted for baseline differences), were similar quantitatively
      and in direction of effect in both age groups. CONCLUSIONS: In A-HeFT, FDC I/H
      improved outcomes in HF patients aged <65 or >=65 years, despite significant
      baseline differences between these age groups. Patients aged >=65 years, a group
      at greater mortality risk, had the greatest survival benefit from FDC I/H.

PMID- 22858075
TI  - Protective effect of carvedilol on adriamycin-induced left ventricular
      dysfunction in children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Adriamycin (ADR) is a potent chemotherapeutic agent widely used in
      the treatment of childhood acute lymphoblastic leukemia (ALL); its clinical use
      is limited owing to its marked cardiotoxicity. The present study investigated the
      possible protective role of carvedilol on ADR-induced left ventricular
      dysfunction in children with ALL. METHODS AND RESULTS: Fifty children with newly
      diagnosed ALL were included in this study. They were divided into 2 equal groups:
      1) ADR; and 2) ADR + carvedilol. Patients were evaluated with conventional 2
      dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and
      2-dimensional longitudinal strain echocardiography (2DS) before and after
      therapy. Plasma lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and
      troponin I levels were also determined before and after therapy. ADR treatment
      reduced left ventricular systolic dysfunction as assessed by a significant
      decrease in fractional shortening (FS) (2D) and global peak-systolic strain
      (GPSS; 2DS). In addition, ADR treatment significantly increased plasma troponin I
      and LDH. Pretreatment of ADR-treated patients with carvedilol resulted in a
      significant increase in FS (2D) and GPSS (2DS). Furthermore, carvedilol
      pretreatment inhibited ADR-induced increase in plasma troponin I and LDH.
      CONCLUSIONS: These results suggested a protective role of carvedilol against ADR
      induced cardiotoxicity.

PMID- 22858076
TI  - Prognostic impact of the addition of ventilatory efficiency to the Seattle Heart
      Failure Model in patients with heart failure.
AB  - BACKGROUND: The Seattle Heart Failure Model (SHFM) is a multivariable model with
      proven prognostic value. Cardiopulmonary exercise testing (CPX) and neurohormonal
      markers (eg, B-type natriuretic peptide [BNP]) are also well accepted assessment
      techniques in the HF population and have both demonstrated robust prognostic
      value. The purpose of this investigation was to assess the combined prognostic
      value of the SHFM and CPX. METHODS AND RESULTS: This study included all 453
      patients enrolled in the Multicenter In-Sync Randomized Clinical Evaluation
      (MIRACLE) trial. Baseline SHFM and CPX were used. Both peak oxygen consumption
      (VO(2)) and ventilatory efficiency (VE/VCO(2)) were determined. In a univariate
      Cox proportional model analysis, SHFM and log-transformed peak VE/VCO(2) were
      stronger predictors of 6-month mortality (both P < .001) than log-transformed BNP
      (P = .013) or peak VO(2) (P = .066). In a multivariable Cox proportional hazards
      model, neither peak VO(2) nor BNP were independent predictors when added to the
      SHFM (P > .1). Conversely, peak VE/VCO(2) was a strong independent predictor when
      added to the SHFM, with an increase in the Cox proportional hazards model Wald
      chi(2) from 22.7 for SHFM alone to 33.8 with inclusion of log-transformed peak
      VE/VCO(2) (P < .0001) and significant changes in the net reclassification
      improvement and integrated discrimination index (both P < .002). CONCLUSIONS:
      These results indicate that the SHFM and peak VE/VCO(2) work synergistically to
      improve prognostic resolution. Further investigation is needed to continue to
      optimize multivariable prognostic models in patients with HF, a chronic disease
      population that continues to suffer from a high adverse event rate despite
      advances in medical care.

PMID- 22858077
TI  - Progression of hyponatremia is associated with increased cardiac mortality in
      patients hospitalized for acute decompensated heart failure.
AB  - BACKGROUND: Although hyponatremia during hospitalization for acute decompensated
      heart failure (ADHF) has been reported to correlate with poor prognosis, few
      studies have examined the effect of progression of hyponatremia on cardiac
      prognosis in ADHF patients who were normonatremic at admission. METHODS AND
      RESULTS: Consecutive ADHF patients (n = 662) categorized as New York Heart
      Association Class III or IV were investigated retrospectively. Of these patients,
      634 who survived to discharge were examined and 531 were normonatremic (serum
      sodium concentration [Na] >= 135 and <= 145 mmol/L) at admission. The 531
      patients were divided into 2 groups: the non-developed group, who remained
      normonatremic at discharge (n = 455), and the developed group, who had progressed
      to hyponatremia (Na < 135 mmol/L) at discharge (n = 76). The cardiac event-free
      rate after 12 months was significantly lower in the developed group than in the
      non-developed group (22% vs. 71%; P < .0001). Although their baseline levels of
      brain natriuretic peptide and left ventricular ejection fraction were similar
      before discharge, the patients in the developed group exhibited higher fractional
      excretion of sodium and received higher doses of diuretics than did those in the
      non-developed group. CONCLUSION: Our data suggest that progression to
      hyponatremia during hospitalization is a robust predictor of poor cardiac
      prognosis in ADHF patients who were normonatremic at admission.

PMID- 22858079
TI  - Spoiler alert: positive small natriuretic peptide--guided therapy sub-study
      ahead: read at your own risk.

PMID- 22858078
TI  - Heart failure outcomes and benefits of NT-proBNP-guided management in the
      elderly: results from the prospective, randomized ProBNP outpatient tailored
      chronic heart failure therapy (PROTECT) study.
AB  - BACKGROUND: Elderly patients with heart failure (HF) have a worse prognosis than
      younger patients. We wished to study whether elders benefit from natriuretic
      peptide-guided HF care in this single-center study. METHODS AND RESULTS: A total
      of 151 patients with HF resulting from left ventricular systolic dysfunction
      (LVSD) were treated with HF treatment by standard-of-care (SOC) management or
      guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a
      goal to lower NT-proBNP <=1000 pg/mL) over 10 months. The primary end point for
      this post-hoc analysis was total cardiovascular events in 2 age categories (<75
      and >=75 years). In those >=75 years of age (n = 38), NT-proBNP values increased
      in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP
      guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC
      management had the highest rate of cardiovascular events, whereas the elderly
      with NT-proBNP management had the lowest rate of cardiovascular events (1.76
      events per patient versus 0.71 events per patient, P = .03); the adjusted
      logistic odds for cardiovascular events related to NT-proBNP-guided care for
      elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted
      logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10).
      CONCLUSIONS: Natriuretic peptide-guided HF care was well tolerated and resulted
      in substantial improvement in cardiovascular event rates in elders
      (ClinicalTrials.Gov #00351390).

PMID- 22858080
TI  - The impact of heart failure on the classification of COPD severity.
AB  - BACKGROUND: Pulmonary restriction-a reduction of lung volumes-is common in heart
      failure (HF), rendering severity grading of chronic obstructive pulmonary disease
      (COPD) potentially problematic in subjects with both diseases. We compared
      pulmonary function in patients with either HF or COPD, or the combination to
      assess whether grading of COPD using the Global Initiative of Chronic Obstructive
      Lung Disease classification is hampered in the presence of HF. METHODS AND
      RESULTS: In 2 cohorts involving 591 patients with established HF and 405 with a
      primary care diagnosis of COPD, the presence of HF and COPD was assessed
      according to guidelines. HF severity was staged according to the NYHA
      classification system into Classes I-IV. COPD was diagnosed if the ratio of post
      bronchodilator forced expiratory volume in 1 second and forced vital capacity
      (FEV1/FVC) was <0.70, and categorized in GOLD stages I-IV according to post
      bronchodilator-predicted FEV1 levels (FEV1% >=80%; 50-79%; 30-49%; <30%). In
      total, 557 patients with HF only, 108 with HF+COPD, and 194 with COPD only were
      studied. Patients, who had neither HF nor COPD according to definition, or HF
      with reversible obstruction in post-bronchodilator pulmonary function tests were
      excluded from this analysis (n = 137). Compared with COPD only, patients with HF
      plus COPD had higher levels of post-bronchodilator FEV1/FVC (median [quartiles]
      0.57 [0.47-0.64] vs 0.62 [0.55-0.66] and lower total lung capacity % (115 [104
      126]% vs 105 [95-117]%, P < .001) P < .001), but comparable levels of post
      bronchodilator FEV1% (70 [56-84]% vs 68 [54-80]%, P = .22) and thus similar
      distributions of GOLD stages I-IV in both groups (24/56/19/4% vs 31/50/19/1%, P =
      .57). In patients with HF only, 25% exhibited pre-bronchodilator FEV1% levels of
      <80% (FEV1% 94 [80-108]%), despite a pre-bronchodilator FEV/FVC ratio >=0.7 in
      this group. The reduction of FEV1 in patients with HF only was associated with HF
      severity. CONCLUSIONS: In stable HF, FEV1 may be significantly reduced even in
      the absence of "real" airflow obstruction. In this situation, diagnosing COPD
      according to GOLD criteria (based on FEV1/FVC) still seems feasible, because both
      FEV1 and FVC are usually decreased to an equal extent in HF. However, classifying
      COPD based on FEV1 levels may overrate obstruction severity in patients with
      combined disease (HF plus COPD), and thus may lead to unjustified use of
      bronchodilators.

PMID- 22858081
TI  - The diversity of heart failure in a hospitalized population: the role of age.
AB  - BACKGROUND: The prevalence of heart failure (HF) among hospitalized elderly
      patients is high and steadily growing. However, because most studies have focused
      mostly on young patients, little is known about the clinical characteristics,
      echocardiographic measures, prognostic factors, and outcome of hospitalized
      elderly HF patients. METHODS AND RESULTS: We identified all HF patients aged >=50
      years who had undergone >=1 echocardiography study and had been hospitalized
      during January 2000 to December 2009. A comparative analysis was performed
      between 3,897 "young" patients (aged 50-75 years) and 5,438 "elderly" patients
      (aged >75 years), followed for a mean 2.8 +/- 2.6 years. Elderly HF patients were
      more often female (50% vs 35%; P < .0001) and had a higher prevalence of HF with
      preserved ejection fraction (64.8% vs 53%; P < .0001), more significant valvular
      disease (35.7% vs 32.5%; P < .0001), and lower rates of ischemic heart disease
      (65.5% vs 70.9%; P < .0001) and diabetes (34.4% vs 53.9%; P < .0001). Thirty-day
      and 1-year mortality rates were significantly higher among the elderly population
      (12.2% vs 6.9% [P < .0001] and 34.3% vs 21.2% [P < .0001], respectively).
      Prognostic markers differed significantly between age groups. Young-specific
      predictors were chronic renal failure, diastolic dysfunction, malignancy, and
      tricuspid regurgitation, whereas elderly-specific predictors were HF with reduced
      ejection fraction, chronic obstructive pulmonary disease, pulmonary hypertension,
      and mitral regurgitation. CONCLUSIONS: Hospitalized elderly, compared with young,
      HF patients differed in prevalence of cardiac and noncardiac comorbid conditions,
      echocardiographic parameters, and predictors of short- and intermediate-term
      mortality. Identifying unique features in the elderly population may render age
      tailored therapeutics.

PMID- 22858082
TI  - Effect of colchicine on myocardial injury induced by Trypanosoma cruzi in
      experimental Chagas disease.
AB  - BACKGROUND: The hallmark of Chagas disease (CD) is multifocal myocarditis and
      extensive fibrosis. We investigated the potential effect of colchicine on
      myocardial remodeling in experimental CD. METHODS AND RESULTS: One hundred Syrian
      hamsters were randomly divided into noninfected untreated control (CG),
      noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage),
      infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1))
      groups. The interstitial collagen volume fraction (ICVF) was evaluated by
      videomorphometry with picrosirius red staining. The gelatinolytic activities of
      matrix metalloproteinase (MMP) 2 were examined with the use of zymography.
      Myocarditis was described according to the Dallas criteria. Statistical
      comparisons were performed with parametric analysis of variance and Tukey test.
      ICVF (%) accumulation was attenuated in infected colchicine-treated animals in
      the left (CG 0.81 +/- 0.13, COLG 0.85 +/- 0.13, IG: 1.35 +/- 0.31,* ICOLG 1.06 +/
      0.19; *P < .05 compared with ICOLG) and right ventricles (CG 1.4 +/- 0.36, COLG
      1.26 +/- 0.14, IG 1.97 +/- 0.058,* ICOLG: 1.52 +/- 0.23; *P < .05 compared with
      ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in
      ICOLG (17,432.8*) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P
      < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG.
      CONCLUSIONS: Colchicine had a protective effect on myocardium, indicated by
      decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and
      attenuated myocardial inflammation.

PMID- 22858083
TI  - Proteomic profiling implies mitochondrial dysfunction in tachycardia-induced
      heart failure.
AB  - BACKGROUND/OBJECTIVES: Molecular mechanisms of congestive heart failure as
      reflected by alterations of protein expression patterns are still incompletely
      analyzed. We therefore investigated intraventricular (ie, left ventricular
      congestive heart failure [LV-CHF] vs. LV-control [CTRL], and right ventricular
      [RV]-CHF vs. RV-CTRL) and interventricular (ie, LV-CHF vs. RV-CHF, and LV-CTRL
      vs. RV-CTRL) protein expression differences in an animal model. METHODS: The
      model of rapid ventricular pacing in rabbits was combined with a proteomic
      approach using 2-dimensional gel electrophoresis. Identification of proteins was
      done by matrix-assisted laser desorption/ionization-tandem mass spectrometry
      (MALDI-MS/MS). RESULTS: Rapid ventricular pacing-induced heart failure was
      characterized by LV dilatation, dysfunction, and hypotension as well as by
      increased BNP gene expression. By comparing LV-CHF vs. LV-CTRL, proteins were
      found to be underexpressed at 3 crucial points of cellular energy metabolism. In
      RV-CHF vs. RV-CTRL, proteins belonging to respiratory chain complexes were
      underexpressed, but additionally a disturbance in the nitric oxide-generating
      enzymatic apparatus was seen. Regarding the interventricular analyses, a stronger
      expression of energetic pathways was accompanied by an underexpression of
      contractile and stress response proteins in failing left vs. right ventricles.
      Finally, significant protein expression differences were found in LV-CTRL vs. RV
      CTRL reflecting a higher expression of contractile, stress response, and
      respiratory chain proteins in LV tissue. CONCLUSIONS: In tachycardia-induced
      heart failure, significant inter- and intraventricular protein expression
      patterns were found with a predominance of proteins, which are involved in
      cellular energy metabolism.

PMID- 22858084
TI  - Aneurysmal subarachnoid hemorrhage in patients under 35-years-old: a single
      center experience.
AB  - OBJECTIVE: Aneurysmal subarachnoid hemorrhage (SAH) is relatively uncommon in
      young adults. There is a paucity of data pertaining to the management of
      aneurysmal SAH in young patients, especially with endovascular therapy. METHODS:
      We reviewed all SAH patients under the age of 35 years treated at Jefferson
      Hospital for Neuroscience, Philadelphia, USA, from 2004 to 2009. RESULTS: A total
      of 40 patients (15 males and 25 females) under the age of 35 were treated for
      aneurysmal SAH. The average patient age was 30 years (17-35 yo); 25 (62.5%) were
      smokers. Seventeen patients presented with a Hunt and Hess Grade I or II (42.5%),
      20 with a Grade III (50%), and 3 with a Grade IV (7.5%). Thirty-two aneurysms
      (80%) were located in the anterior circulation and 8 (20%) in the posterior
      circulation. Thirty-five patients (87.5%) were treated with coil embolization
      versus 5 with craniotomy and clipping. The endovascular and microsurgical
      occlusion rates were 90.6% and 100%, respectively. There were no procedural
      complications with endovascular therapy. Of 35 patients undergoing endovascular
      treatment, 24 (68.6%) had excellent outcomes at time of discharge with a Glasgow
      outcome scale of 5. There were no deaths in the series. No patient experienced a
      rehemorrhage after endovascular treatment. CONCLUSION: Smoking, female sex, and
      anterior circulation aneurysms are highly prevalent in young adults with SAH.
      Endovascular treatment resulted in an overall favorable outcome with no
      rehemorrhages in patients under the age of 35 years. Our results suggest that
      endovascular therapy is a reasonable treatment for young patients with SAH.

PMID- 22858085
TI  - Endoscopic supracerebellar infratentorial parapineal approach for third
      ventricular colloid cyst in a patient with quadrigeminal cistern arachnoid cyst:
      Case report.

PMID- 22858086
TI  - [Health 2.0: new communication tools for professional practice in a hospital
      pharmacy].

PMID- 22858087
TI  - [Sealing with 70% alcohol in catheter-related infection in home parenteral
      nutrition].

PMID- 22858088
TI  - [Carglumic acid for treatment of valproic acid-induced hyperammonaemia in a
      paediatric patient].

PMID- 22858089
TI  - [Analysis of adherence and efficiency when replacing an antiretroviral therapy
      with efavirenz-emtricitabine-tenofovir in a single daily dose].
AB  - OBJECTIVE: To analyse whether the change of antiretroviral therapy to
      efavirenz/emtricitabine/tenofovir in a single daily dose (EETu) increases
      adherence and maintains effectiveness, and establish the cost increase caused by
      the change. METHODS: An observational, retrospective, and intra-subject study,
      performed in the outpatient dispensing unit. The study period was 1 year (6
      months before and 6 months after the change). Computer dispensing records and
      days of hospitalisation during the study period were reviewed, and the difference
      in treatment adherence calculated. To determine the effectiveness of treatment,
      viral load and CD4 lymphocytes data before and after the change were reviewed.
      The cost before and after treatment for each patient was determined, and
      therefore the annual cost increase and the incremental cost per patient. RESULTS:
      The study included 127 patients. The difference in adherence was 0.6%. The
      percentage of poor adherence was 35.4% and 40.9% before and after the treatment
      change, respectively. The levels of CD4 lymphocytes and viral load did not change
      significantly with treatment. The economic analysis revealed an annual increase
      of 25,374.60 and ?199.80 per patient. CONCLUSIONS: The use of EETu did not
      improve the control of HIV infection in terms of effectiveness and adherence, and
      resulted in increased economic costs. Therefore, its choice as antiretroviral
      treatment will have to be based on criteria other than those described above.

PMID- 22858090
TI  - [Topical sirolimus 0.4% formulation for treatment of facial angiofibromas].

PMID- 22858091
TI  - Rich man, poor man: developmental differences in attributions and perceptions.
AB  - In an examination guided by cognitive developmental and attribution theory of how
      explanations of wealth and poverty and perceptions of rich and poor people change
      with age and are interrelated, 6-, 10-, and 14-year-olds (N=88) were asked for
      their causal attributions and trait judgments concerning a rich man and a poor
      man. First graders, like older children, perceived the rich man as more competent
      than the poor man. However, they had difficulty in explaining wealth and poverty,
      especially poverty, and their trait perceptions were associated primarily with
      their attributions of wealth to job status, education, and luck. Fifth and ninth
      graders more clearly attributed wealth and poverty to the equity factors of
      ability and effort and based their trait perceptions on these attributions.
      Although the use of structured attribution questions revealed more understanding
      among young children than previous studies have suggested, the findings suggest a
      shift with age in the underlying bases for differential evaluation of rich and
      poor people from a focus on good outcomes associated with wealth (a good
      education and job) to a focus on personal qualities responsible for wealth
      (ability and effort).

PMID- 22858092
TI  - Vulnerability to violence of Talibe children in Mauritania.

PMID- 22858093
TI  - Intimate partner violence exposure, salivary cortisol, and childhood asthma.
AB  - OBJECTIVES: Neuroendocrine alterations may help explain health differences
      between intimate partner violence (IPV) exposed children and non-exposed
      children. We sought to determine the feasibility of having families, recruited at
      a child asthma visit, collect at home and return via mail child salivary samples,
      and whether socio-demographic variables were associated with sample return. For
      those returning samples, we examined whether past-year IPV exposure was
      associated with total cortisol output (AUC) and the magnitude of the cortisol
      awakening response (CAR), and whether these cortisol values were associated with
      asthma control. METHODS: Fifty-five families with an asthmatic child of any age
      were recruited from 2 pediatric asthma clinics. At the time of the visit, parents
      completed a survey packet which included a modified version of the Conflict
      Tactics Scale to assess IPV. Parents were given supplies to collect 3 child
      salivary cortisol samples (awakening, 30-min after awakening, bedtime) at home on
      a typical day, and return them via mail. Medical records also were abstracted.
      RESULTS: Fifty-three percent (n=29) returned child salivary samples. Families who
      returned samples typically returned them within 2 weeks, most commonly before we
      made a reminder call. Parental male sex was associated (p=.06) with increased
      rate of return at the trend level. In multivariable models, a 1-unit increase in
      IPV was significantly associated with a .93 SD increase in root-transformed total
      cortisol output (AUC) (un-standardized beta=2.5; SE .59; p=.001). The odds of
      uncontrolled asthma were marginally higher for every nmol/l increase in CAR (OR
      1.04; 95% CI 1.0, 1.1; p=.06). CONCLUSIONS: This study provides support for the
      feasibility of obtaining a moderate return of salivary specimens from a
      convenience sample. Findings that IPV was associated with elevated total cortisol
      output and uncontrolled asthma was marginally associated with cortisol awakening
      response suggest that future studies should investigate whether cortisol mediates
      the IPV-child asthma relationship.

PMID- 22858094
TI  - Analysis of the relationship between neonaticide and denial of pregnancy using
      data from judicial files.
AB  - OBJECTIVES: Using judicial files on neonaticides, (1) to examine the frequency of
      the association between neonaticide and denial of pregnancy; (2) to assess the
      accuracy of the concept of denial of pregnancy; (3) to examine its usefulness in
      programs to prevent neonaticides. METHODS: Quantitative and qualitative analyses
      of data collected from judicial files during a population-based study carried out
      in 26 courts in 3 regions of France over a 5-year period. RESULTS: There were 32
      cases of neonaticides identified; 24, perpetrated by 22 mothers, were solved by
      police investigation. Aged 26 years on average, the mothers had occupations that
      resembled those of the general population and 17 had jobs, 13 were multiparous
      and 11 lived in a couple relationship. No effective contraception was used by
      women in 20 cases. Psychopathology was rare but mothers shared a personality
      profile marked by immaturity, dependency, weak self esteem, absence of affective
      support, psychological isolation and poor communication with partners. No
      pregnancy was registered nor prenatal care followed. Two (perhaps 3) pregnancies
      were undiscovered until delivery. No typical denial of pregnancy was observed in
      the other cases. Pregnancies were experienced in secrecy, with conflicting
      feelings of desire and rejection of the infant and an inability to ask for help.
      Those around the mothers, often aware of the pregnancy, offered none. In the
      absence of parallel clinical data, it is not possible to calculate the frequency
      of the association between neonaticide and denial of pregnancy. CONCLUSIONS: The
      term 'denial of pregnancy' cannot fully reflect the complexity of emotions and
      feelings felt by all perpetrators of neonaticide and is used differently by
      different professionals. The term itself and its excessive generalization
      contribute to pathologizing women while absolving those around them and has
      little operational value in preventing neonaticides. The authors suggest
      rethinking the terms presently used to describe the phenomenon of pregnancy
      denial.

PMID- 22858095
TI  - Insights into the recognition of the human glycome by microbial carbohydrate
      binding modules.
AB  - Mammalian glycans are often very complex and consequently both commensal bacteria
      and bacterial pathogens have developed specialized and often elaborate
      carbohydrate-active enzyme (CAZyme) systems to interact with these sugars. These
      enzymes are frequently multimodular, with modular functions most often conferring
      catalysis (glycoside hydrolase catalytic modules) or carbohydrate-binding
      (carbohydrate-binding modules or CBMs). Structure-function studies of five CBM
      families are revealing specificities for complex mammalian carbohydrates. Three
      of these CBM families (32, 47, and 51) show significant structural identity
      between their beta-sandwich folds, suggesting a shared evolutionary precursor,
      but have divergent binding specificities. The family 40 and 41 CBMs recognize
      sialic acid and glycogen, respectively, through different modes of sugar binding,
      though they also adopt all beta-structure folds. A structural view of new models
      generated for complete CAZymes suggests three distinct modes of CBM deployment:
      (i) formation of the catalytic site, (ii) coordinated catalysis and binding, and
      (iii) general substrate adherence.

PMID- 22858096
TI  - The development of first Staphylococcus aureus SplB protease inhibitors:
      phosphonic analogues of glutamine.
AB  - Produced by Staphylococcus aureus, SplB belongs to the chymotrypsin-like serine
      protease family. Since the biological role of SplB protease is unknown, the
      design and application of its specific inhibitors may help to reveal the function
      of this enzyme. Until now no SplB inhibitors have been reported. Herein, we
      present the design and synthesis of novel alpha-aminophosphonic analogues of
      glutamine, as well as their peptidyl derivatives. The inhibitory effects of these
      compounds towards the newly discovered SplB serine protease from S. aureus are
      characterized. We have also investigated the influence of aromatic ester
      substituents on inhibitory potency towards SplB. One of the compounds-Cbz-Glu-Leu
      Gln(P)(OC(6)H(4)-4-O-CH(3))(2)-displayed an apparent second-order inhibition rate
      value of 1400 M(-1)s(-1).

PMID- 22858097
TI  - Synthesis and anti-HIV activities of symmetrical dicarboxylate esters of
      dinucleoside reverse transcriptase inhibitors.
AB  - Three nucleoside analogues, 3'-fluoro-2',3'-dideoxythymidine (FLT), 3'-azido
      2',3'-dideoxythymidine (AZT), and 2',3'-dideoxy-3'-thiacytidine (3TC) were
      conjugated with three different dicarboxylic acids to afford the long chain
      dicarboxylate esters of nucleosides. In general, dinucleoside ester conjugates of
      FLT and 3TC with long chain dicarboxylic acids exhibited higher anti-HIV activity
      than their parent nucleosides. Dodecanoate and tetradecanoate dinucleoside ester
      derivatives of FLT were found to be the most potent compounds with EC(50) values
      of 0.8-1.0 nM and 3-4 nM against HIV-1(US/92/727) and HIV-1(IIIB) cells,
      respectively. The anti-HIV activity of the 3TC conjugates containing long chain
      dicarboxylate diester (EC(50)=3-60 nM) was improved by 1.5-66 fold when compared
      to 3TC (EC(50)=90-200 nM). This study reveals that the symmetrical ester
      conjugation of dicarboxylic acids with a number of nucleosides results in
      conjugates with improved anti-HIV profile.

PMID- 22858098
TI  - Identification of a novel serum and glucocorticoid regulated kinase-1 (SGK1)
      ligand from virtual screening.
AB  - The serum and glucocorticoid regulated kinase-1 (SGK1) is part of the
      serine/threonine kinase family and has therapeutic potential in several
      neurodegenerative diseases such as ischemic stroke and Parkinson's disease. Here
      we use structure-based virtual screening to identify a novel ligand which
      inhibits SGK1 activity. The data presented here can be used for future scaffold
      hopping and possible drug development efforts.

PMID- 22858099
TI  - Discovery of potent and selective rhodanine type IKKbeta inhibitors by hit-to
      lead strategy.
AB  - Regulation of NF-kappaB activation through the inhibition of IKKbeta has been
      identified as a promising target for the treatment of inflammatory and autoimmune
      disease such as rheumatoid arthritis. In order to develop novel IKKbeta
      inhibitors, we performed high throughput screening toward around 8000 library
      compounds, and identified a hit compound containing rhodanine moiety. We modified
      the structure of hit compound to obtain potent and selective IKKbeta inhibitors.
      Throughout hit-to-lead studies, we have discovered optimized compounds which
      possess blocking effect toward NF-kappaB activation and TNFalpha production in
      cell as well as inhibition activity against IKKbeta. Among them, compound 3q
      showed the potent inhibitory activity against IKKbeta, and excellent selectivity
      over other kinases such as p38alpha, p38beta, JNK1, JNK2, and JNK3 as well as
      IKKalpha.

PMID- 22858100
TI  - Diaminopropionic acid lipopeptides: characterization studies of polyplexes aimed
      at pDNA delivery.
AB  - Here we report a novel class of peptides-d-diaminopropionic acids (Dap)-for gene
      delivery. These peptides have attractive properties for gene delivery, and the
      advantage that they can be easily manipulated in relation to their composition,
      abiding with tailored-design. We characterized the toxicological and biophysical
      properties of DNA particles resulting from the interaction of the nucleic acid
      with a series of Dap(8) peptides conjugated to different alkyl groups. These
      peptides formed small and homogenous DNA particle populations that protected
      against DNase I degradation at non-toxic concentrations. However, despite the
      similarity between these peptides and others that are arginine-rich, and
      efficient vectors, functional studies suggest the need for additional
      modifications in the carriers to improve their DNA delivery efficiency. Taken
      together, these studies underscore the relevance of the overall structure of the
      carrier and the complexity of designing from scratch a carrier.

PMID- 22858101
TI  - Synthesis and characterization of quinoline-based thiosemicarbazones and
      correlation of cellular iron-binding efficacy to anti-tumor efficacy.
AB  - Iron chelators have emerged as a potential anti-cancer treatment strategy. In
      this study, a series of novel thiosemicarbazone iron chelators containing a
      quinoline scaffold were synthesized and characterized. A number of analogs show
      markedly greater anti-cancer activity than the 'gold-standard' iron chelator,
      desferrioxamine. The anti-proliferative activity and iron chelation efficacy of
      several of these ligands (especially compound 1b), indicates that further
      investigation of this class of thiosemicarbazones is worthwhile.

PMID- 22858102
TI  - Synthesis and antibacterial activity of 6-O-(heteroaryl-isoxazolyl)propynyl 2
      fluoro ketolides.
AB  - Macrolide antibiotics are widely prescribed for the treatment of respiratory
      tract infections; however, the increasing prevalence of macrolide-resistant
      pathogens is a public health concern. Therefore, the development of new macrolide
      derivatives with activities against resistant pathogens is urgently needed. A
      series of novel 6-O-(heteroaryl-isoxazolyl)propynyl 2-fluoro ketolides has been
      synthesized from erythromycin A. These compounds have shown very promising in
      vitro and in vivo antibacterial activities against key respiratory pathogens
      including erythromycin-susceptible/resistant strains.

PMID- 22858103
TI  - Fate of isotopically labeled zinc oxide nanoparticles in sediment and effects on
      two endobenthic species, the clam Scrobicularia plana and the ragworm Hediste
      diversicolor.
AB  - Although it is reported that metal and metal oxide nanoparticles, which are among
      the most rapidly commercialized materials, can cause toxicity to organisms, their
      fate in the environment and toxicity to marine organisms are not well understood.
      In this study, we used a stable isotope labelling approach to trace the fate of
      nanoparticles (NPs) in sediments and also investigated bio-uptake in two
      estuarine intra-sedimentary invertebrates Scrobicularia plana and Nereis
      diversicolor. We selected exposure to 3 mg kg(-1) sediment ZnO NPs since this
      level is a realistic prediction of the environmental concentration in sediments.
      67ZnO NPs (DLS: 21-34 nm, positively charged: 31.3 mV) suspensions were
      synthesised in diethylene glycol (DEG). We explored the fate of 67ZnO NPs in
      sediment, 67Zn bioaccumulation and the biochemical (biomarkers of defence and
      damage) and behavioural (burrowing kinetics and feeding rates) biomarkers in both
      species to 67ZnO NPs and DEG on its own during a 16 d laboratory exposure. After
      exposure, 67Zn concentrations in sediment showed higher levels in the upper
      section (1cm: 2.59 mg kg(-1)) decreasing progressively (2 cm: 1.63 mg kg(-1), 3
      cm: 0.90 mg kg(-1), 4 cm: 0.67 mg kg(-1)) to a minimum value at the bottom (5 cm:
      0.31 mg kg(-1)). 67Zn bioaccumulation was observed in both organisms exposed to
      67ZnO NPs in DEG but no major inter-species differences were found. At the
      biochemical level, 67ZnO NPs exposure significantly induced increased glutathione
      S-transferase activity in worms and catalase activity in clams whereas superoxide
      dismutase activity and thiobarbituric acid reactive substance levels were not
      affected in any species. Exposure to DEG on its own leads to a significant
      increase of metallothionein-like protein levels in clams compared with those
      exposed to 67ZnO NPs or controls. Burrowing behaviour as well as feeding rate
      were significantly impaired in both species exposed to 67ZnO NPs. Concerning
      exposure to DEG on its own, burrowing behaviour impairments were also shown in
      both species and feeding rate was impaired in bivalves. At environmentally
      realistic concentration of 67ZnO NPs in sediment, there is no strong evidence for
      a severe nanoparticle effect since most effects were also observed in the
      presence of DEG alone.

PMID- 22858104
TI  - Environmental hazard assessment of coal fly ashes using leaching and ecotoxicity
      tests.
AB  - The environmental hazard of six coal fly ash samples collected from various coal
      incineration plants were examined in the present study, using various leaching
      tests along with physicochemical and ecotoxicological analyses. Physicochemical
      analyses indicated that the concentration of Ba, Cr, Mo, Se, sulfates and total
      dissolved solids (TDS) exceeded the threshold values, according to the European
      Council decision 2003/33/EC for inert, non-hazardous or hazardous waste. The
      highest sensitivity, among examined organisms, was presented by Daphnia magna and
      was ascribed to the lowest tolerance of the organism to Cr. The toxic effect
      profile of the leachates toward Vibrio fischeri revealed that its bioluminescence
      was significantly altered by the presence of heavy metals in the leachates (such
      as Cu, Ni and Zn) in low or sub-lethal doses. Although the toxicity of the
      leachates toward Pseudokirchneriella subcapitata was relatively high, the
      correlation between the toxicity and heavy metals concentration was rather poor,
      indicating the significance of the bioavailability of constituents and the
      importance of toxicity testing. Based on the classification of the samples
      resulted by physicochemical analyses of the leachates and the results of
      ecotoxicity tests, Physicochemical and Ecotoxicological indices were also
      defined, for an overall evaluation of the environmental impact assessment of fly
      ashes. The suggested indices showed that ecotoxicity tests were in some cases
      inconsistent with the outcome of waste classification based on physicochemical
      analyses. Moreover, the examination of leaching protocols and obtained results
      showed that one stage leaching test (L/S=10 L/kg) underestimated the fly ash
      classification, when compared with the two stage test EN 12457-3 at the
      cumulative ratio L/S=10 L/kg. In addition, the application of availability test
      NEN 7341 provided useful results about the ecotoxicity wastes. Thus, NEN 7341 is
      strongly suggested for the implementation of such studies, since the
      bioavailability of constituents may not be altered by pH adjustment tactics and
      pH-originated toxicity effects may be avoided.

PMID- 22858105
TI  - A lower limit of detection for atrazine was obtained using bioluminescent
      reporter bacteria via a lower incubation temperature.
AB  - The present article reports on the influence of various atrazine concentrations
      to the response of genetically modified Escherichia coli TV1061 bacterial cells
      while modulating the experimental conditions. Interesting increases of
      bioluminescence signals are recorded for E. coli TV1061 bacteria in the presence
      of 10 MUg/mL atrazine concentration named "high-toxicity bacteria alert" when
      compared with 1 MUg/mL -10 fg/mL atrazine termed "low-toxicity bacteria alert".
      Detecting the effect of atrazine via its effect on bioluminescence of bacteria
      has been carried out by two consecutive measurements (fresh and overnight modes)
      at different concentrations of analyte. We have shown that a more precise
      discrimination at lower-toxicity concentrations can be obtained through overnight
      incubation of bacteria with the analyte at 4  degrees C. In addition,
      centrifugation of bacterial cells and analyte dilutions has been performed in
      order to ensure a better interaction between the insoluble atrazine pesticide and
      the bacterial cells.

PMID- 22858106
TI  - Psychiatric disorder and suicide in the military, then and now: commentary on
      Frueh and Smith.
AB  - Consulting archival medical data from the American Civil War, Frueh and Smith
      found little evidence of mental disorders, no evidence of reexperiencing symptoms
      suggestive of posttraumatic stress disorder, but a notable rate of suicide. In
      this commentary, I suggest reasons why the archives contain so few traces of
      combat-related disorders despite the massive trauma experienced by soldiers in
      the Civil War, and I draw implications for military personnel returning from the
      wars in Iraq and Afghanistan.

PMID- 22858107
TI  - Reliability of a new method for lower-extremity measurements based on
      stereoradiographic three-dimensional reconstruction.
AB  - INTRODUCTION: Several clinical and radiological techniques have been described to
      assess lower limb length and angle measurements. None of them has yet met the
      ideal criteria for a reliable, reproducible, safe, and inexpensive system. In
      this context, a new biplanar X-ray system (EOSTM, EOS imaging, Paris, France)
      makes it possible to obtain a 3D reconstruction of the lower extremities from two
      2D orthogonal radiographic images, with associated calculation of 3D
      measurements. The reliability of this technique has never been documented on
      adults. HYPOTHESIS: Lower limb measurements produced by the 3D EOSTM
      reconstruction system are reproducible regarding inter- and intraobserver
      assessment and more reliable with this 3D technique than when they are obtained
      from 2D measurements. MATERIALS AND METHODS: This study included 25 patients
      awaiting total hip arthroplasty (50 lower limbs). Two independent observers made
      all measurements twice, both on the 2D frontal radiograph and using 3D
      reconstructions (femoral measurements of length, offset, neck shaft angle, neck
      length, and head diameter, as well as the tibia length, limb length, HKA and
      HKS). Reproducibility was estimated by intraclass correlation coefficients.
      RESULTS: Both the inter- and intraobserver reproducibility of the EOSTM
      measurements was excellent; more specifically inter- and intraobserver
      reproducibility was 0.997 and 0.997 for femoral length, 0.996 and 0.995 for
      tibial length, 0.999 and 0.999 for limb length, 0.894 and 0.891 for HKS, 0.993
      and 0.994 for HKA, 0.870 and 0.845 for femoral offset, and 0.765 and 0.851 for
      neck shaft angle. For most of the variables, the interobserver correlations were
      statistically better with the EOSTM 3D reconstruction. DISCUSSION: Our results
      show that the EOSTM systems allow reproducible lower limb measurements.
      Furthermore, 3D EOSTM reconstructions offer better reproducible measures for most
      of the parameters than radiographic 2D projection. Its use before deciding on
      surgery and during planning for lower limb arthroplasty appears essential to us.
      LEVEL OF EVIDENCE: Level III: diagnostic prospective study on consecutive
      patients.

PMID- 22858108
TI  - A ganglion cyst generated by non-absorbable meniscal repair suture material.
AB  - Arthroscopic meniscal repair has been a common procedure for the treatment of a
      torn meniscus, since the importance of meniscal preservation is widely
      understood. Over the years, the complications associated with suture material
      have been reported. Meniscal cyst is also one of those things. But ganglion cyst
      triggered by non-absorbable suture material was not documented in the literature.
      We report the case of a 19-year-old boy who underwent arthroscopic ACL
      reconstruction and repair of the medial meniscus by inside-out technique using 2
      0 non-absorbable polyester sutures. The patient returned to our clinic at 4-year
      F/U with right knee pain due to medial meniscus tear and ganglion cyst. We
      suspect non-absorbable suture materials itself might have caused soft tissue
      irritation with repetitive trauma that lead to mucoid degeneration which results
      in ganglion cyst formation in the end.

PMID- 22858109
TI  - Free vascularised fibular graft in multi-operated patients for an aseptic non
      union of the humerus with segmental defect: Surgical technique and results.
AB  - In cases of non-union of the humerus with segmental bone defect, if a
      conventional treatment has failed, free fibular transfer should be considered as
      a reliable option to allow satisfactory bone union. We reported five cases of
      aseptic and multi-operated non-union of the humerus from trauma. In each case, a
      free fibular flap was performed after failure of a conventional treatment and
      bony union was demonstrable radiologically within six months. Some technical
      points such as harvesting of the fibula, humerus approach, fibula placement and
      fixation are highlighted in order to simplify the transfer and to standardise the
      technique.

PMID- 22858110
TI  - Comments on: "Arthroscopic treatment of rotator cuff tear in the over-60s: Repair
      is preferable to isolated acromioplasty-tenotomy in the short term," by C.
      Dezaly, F. Sirveaux, R. Philippe, F. Wein-Remy, J. Sedaghatian, O. Roche and D.
      Mole, published in Orthop Traumatol Surg Res 2011;97S:S125-30.

PMID- 22858111
TI  - Fracture of the lower cervical spine in patients with ankylosing spondylitis:
      Retrospective study of 19 cases.
AB  - INTRODUCTION: Controversy exists surrounding optimal treatment of cervical spine
      fractures secondary to ankylosing spondylitis (AS). HYPOTHESIS: The anterior
      approach is an effective surgical technique for these fractures and can be used
      to correct the AS-induced cervical-thoracic kyphosis. MATERIALS AND METHODS: This
      continuous, retrospective series between 1990 and 2010 included 19 patients aged
      33 to 84 years who presented with a lower cervical spine fracture in the context
      of AS. The average follow-up was 45 months. Sixteen of these patients were
      surgically treated using an anterior approach and anterior fixation. In five
      patients without any neurological deficit, their cervical-thoracic kyphosis was
      corrected during the same surgery. Regional kyphosis was measured before the
      surgery, immediately after the surgery and at the last follow-up. RESULTS: Five
      deaths occurred; these were all patients with post-traumatic complete
      quadriplegia. Most the incomplete neurological problems improved (66%). In no
      cases did the neurological condition worsen. Among the 16 patients operated with
      the anterior approach, two patients also required an additional procedure with a
      posterior approach because of a persistent neurological deficit. The fractures in
      the operated patients who survived (14 patients) had healed within an average 4
      month delay (range 3-7 months), without worsening of the kyphosis at final follow
      up. In the five cases where the kyphosis was corrected, the correction averaged
      26 degrees  (range 18-36 degrees ); there were no neurological complications.
      DISCUSSION: Based on these results, we suggest using the anterior approach to
      perform internal fixation as a treatment for cervical fractures secondary to AS
      and to correct the cervical-thoracic kyphosis in patients without neurological
      deficits. LEVEL OF EVIDENCE: Level IV - retrospective study.

PMID- 22858112
TI  - [Predictive value of intraepithelial (CD3) T-lymphocyte infiltration in resected
      colorectal cancer].
AB  - INTRODUCTION: Colorectal cancer (CRC) can induce an anti-tumoral immune response
      mediated by T-lymphocytes, which express CD3. OBJECTIVES: To analyze the
      prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall
      and in the early tumoral stages. METHODS: We revised 251 patients with resected
      CRC and favorable clinical course. CD3I expression was analyzed by
      immunohistochemistry. Multivariate analysis was used to analyze the variables
      independently associated with survival. We analyzed CD3I(+) expression in
      relation to survival and tumoral progression, both overall and in patients with
      pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative
      predictive values and diagnostic accuracy of CD3I expression were analyzed.
      RESULTS: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow
      up of 74 months, CD3I(+) expression showed a favorable prognostic value for
      survival in the multivariate analysis (p=0.045). Survival curves and absence of
      tumoral progression were more favorable in CD3I(+) cases, both overall (p=0.009
      and p=0.004, respectively), and in stages I-II (p=0.029 and p=0.015). The
      specificity and positive predictive value of CD3I(+) were as follows: Survival:
      overall: specificity =0.89; positive predictive value =0.91. Stage (I-II):
      specificity =0.94; positive predictive value =0.98. Absence of tumoral
      progression: overall: specificity=0.89; positive predictive value =0.88. Stage (I
      II): specificity =0.92; positive predictive value =0.96. CONCLUSIONS: CD3I
      expression has an favorable independent prognostic value, with statistically
      significantly higher percentages of survival and absence of tumoral progression.
      This more favorable outcome is maintained in the less advanced stages (I-II).
      CD3I expression shows high specificity and positive predictive value.

PMID- 22858113
TI  - Immune biomarkers in immunotherapeutic trials for type 1 diabetes: cui prodest?
AB  - Decades of research efforts aimed at upgrading type 1 diabetes (T1DM) treatment
      did not harvest much success besides improving insulin therapy, which remains the
      standard of care since 1922. Immunological strategies targeting autoimmune
      mechanisms, rather than their metabolic consequences, are highly demanded. A
      dealt of preclinical studies in animal models offered some promises, which were
      however not maintained once translated into human. All these immune intervention
      trials evaluated metabolic and clinical endpoints, namely C-peptide secretion,
      HbA(1c) and insulin requirements. While critical, we argue that these endpoints
      are insufficient and should be complemented with immune surrogate endpoints, i.e.
      biomarkers reflecting the immune modifications induced by such treatments. This
      is even more critical when clinical expectations are not met, in order to sort
      out the reasons of such failure, i.e. whether immune changes are not accomplished
      or whether, despite being accomplished, they are insufficient to translate into
      clinical benefits. Furthermore, these ancillary analyses may give precious
      indications to design further trials, i.e. to enroll patients with the best odds
      to respond to therapy and to follow-up their response.

PMID- 22858114
TI  - HRS/ACCF expert consensus statement on pacemaker device and mode selection.
      Developed in partnership between the Heart Rhythm Society (HRS) and the American
      College of Cardiology Foundation (ACCF) and in collaboration with the Society of
      Thoracic Surgeons.

PMID- 22858115
TI  - Polyethylene glycol treatment promotes metabolic events associated with maize
      callus morphogenic competence.
AB  - Metabolic changes were studied, which accompanied the conversion of 6month old
      HiII maize non-regenerable (NR) calli into regenerable (R) calli when cultured
      for 63days with 10% polyethylene glycol (PEG) (3350MW) in culture medium. The
      conversion of 6month old NR to R callus morphotype caused by PEG application
      decreased cell wall contents in callus dry mass and changed cell wall phenolics
      making their profile similar to that of R callus by reduction of lignin and ester
      and ether-bound phenolic concentrations, including p-coumaric acid and ester-
      and ether-bound diferulates and by increase of the ratios of ester- and ether
      bound ferulic acid/coumaric acid and ferulic acid/diferulic acid in cell walls of
      NR callus. Some similar changes of cell wall phenolics caused by PEG application
      were also found in 48month old NR callus, that changed the morphology, but did
      not regenerate plants. However, there were no changes in the old callus in levels
      of total ester and ether-bound cell wall phenolics and substantially smaller
      decreases were found in ratios of ester- and ether-bound ferulic acid/coumaric
      acid and ferulic acid/diferulic acid, as well as in diferulate concentrations
      compared to young NR callus cultured with PEG. Remarkably, application of PEG
      also changed the primary metabolism of young NR callus tissues, so that they
      acquired metabolic features of highly regenerable callus. These data clearly
      suggest that PEG alters metabolism of NR calli, so they acquire biochemical
      characteristics of R calli, and that adaptive osmotic adjustments vary in
      different types of callus tissues.

PMID- 22858116
TI  - Limitations and pitfalls of antimullerian hormone measurements.

PMID- 22858117
TI  - Flotation of marine microalgae: effect of algal hydrophobicity.
AB  - This study aims to understand the underlying reasons for the poor flotation
      response of marine microalgae. The flotation performance and hydrophobicity of a
      freshwater microalga (Chlorella sp. BR2) were compared to those of a marine
      microalga (Tetraselmis sp. M8) at different salinities in the presence of a
      cationic collector, tetradecyl trimethylammonium bromide. It was found that
      microalgal hydrophobicity played a more important role than salinity in
      determining the flotation performance.

PMID- 22858118
TI  - Novel mechanisms of EBV-induced oncogenesis.
AB  - Epstein-Barr virus is an etiologic factor in multiple types of cancer that
      primarily develop in lymphocytes and epithelial cells. The tumors are latently
      infected yet express distinct subsets of viral proteins that are essential for
      transformation. The viral oncogenes may be expressed in a subset of cells and are
      transferred through exosomes to many cells to induce growth and alter the tumor
      environment. In some of the viral cancers, viral proteins are not expressed,
      however, the viral miRNAs can alter growth by decreasing expression of negative
      regulators of cell growth such as tumor suppressors and cellular proteins that
      induce apoptosis.

PMID- 22858119
TI  - eSwab flocked swabs unfit for viral culture.

PMID- 22858120
TI  - An objective assessment of the perceived quality of life of living with bilateral
      mastectomy defect.
AB  - BACKGROUND: Mastectomy is a common treatment for breast cancer. We set out to
      quantify the health state utility assessment of living with bilateral mastectomy
      using previously described validated methods. METHODS: Utility assessments using
      visual analogue scale (VAS), time trade-off (TTO), and standard gamble (SG) were
      used to obtain utilities for mastectomy, monocular blindness and binocular
      blindness from a prospective sample of the general population and medical
      students. RESULTS: All measures (VAS, TTO, SG) for mastectomy (0.70 +/- 0.18,
      0.85 +/- 0.16, and 0.86 +/- 0.17, respectively) of the 120 volunteers were
      significantly different (p < 0.0001) from the corresponding scores for binocular
      blindness (0.38 +/- 0.17, 0.67 +/- 0.24, and 0.69 +/- 0.23, respectively).
      Utility scores for mastectomy were not statistically different (p > 0.05) when
      compared to those for monocular blindness (0.67 +/- 0.13, 0.86 +/- 0.15, and 0.86
      +/- 0.15, respectively). Age, gender, race, and income were not statistically
      significant independent predictors of utility scores. Medical education was
      associated with statistically significant higher SG compared to general
      population (0.90 +/- 0.11 versus 0.84 +/- 0.19; p < 0.05). CONCLUSION: In a
      sample of the general population and medical students, utility assessments for
      living with bilateral mastectomy were comparable with those of living with the
      loss of sight from one eye. Our sample population, if faced with living with
      bilateral mastectomy, would consent to undergo a procedure such as breast
      reconstruction with a theoretical 14 percent chance of mortality and be willing
      to trade 5.4 years of existing life-years for such a procedure.

PMID- 22858121
TI  - Differences in sleep disturbance, fatigue and energy levels between women with
      and without breast pain prior to breast cancer surgery.
AB  - The purpose of this study was to evaluate for differences in occurrence and
      severity ratings of sleep disturbance, fatigue, and decreased energy in women who
      reported breast pain prior to surgery for breast cancer. Of the 390 women who
      completed self-report measures for each symptom, 28.2% reported pain in their
      breast prior to surgery. A higher percentage of women in the pain group (i.e.,
      66.7% versus 53.5%) reported clinically meaningful levels of sleep disturbance.
      However, no between group differences were found in the severity of sleep
      disturbance, fatigue, or decreased energy. Findings from this study suggest that
      sleep disturbance, fatigue, and decreased levels of energy are significant
      problems for women prior to breast cancer surgery. Future studies need to
      evaluate for specific characteristics that place women at greater risk for these
      symptoms as well as the mechanisms that underlie these symptoms.

PMID- 22858122
TI  - Metals concentrations in Nile tilapia Oreochromis niloticus () from illegal fish
      farm in Al-Minufiya Province, Egypt, and their effects on some tissues
      structures.
AB  - This study clarified the suitability of fishes caught from illegal fish farms to
      human consumption and their hazards to public health. For this purpose, the
      concentrations of some metals (Al, Cd, Pb, Hg and Ni) in water and Nile tilapia
      (Oreochromis niloticus) fish samples collected from an illegal fish farm, in
      addition to pathological conditions of the fish tissues, were examined. The
      illegal farm water was found to be heavily polluted with metals which far
      exceeded the permissible limits. It was found that metals accumulated in tissues
      of O. niloticus in concentrations higher than those of farm water. Kidney of O.
      niloticus contained the highest concentrations of the detected metals, while
      muscle and skin contained the lowest concentrations. The examination of fish
      tissues revealed various histopathological lesions which related directly to the
      pollution of the illegal farm water. Moreover, metals levels in O. niloticus
      muscle were higher than the maximum permissible levels for human consumption.
      Consequently, the flesh of fishes from the illegal farms could be considered
      hazardous to human health. Therefore, warning against eating fish caught from the
      illegal fish farms should be announced. Moreover, removal of such illegal fish
      farms is necessary for the public health protection.

PMID- 22858123
TI  - Infectious keratitis progressing to endophthalmitis: a 15-year study of
      microbiology, associated factors, and clinical outcomes.
AB  - PURPOSE: To describe the incidence, microbiology, associated factors, and
      clinical outcomes of patients with infectious keratitis progressing to
      endophthalmitis. DESIGN: Nonrandomized, retrospective, consecutive case series.
      PARTICIPANTS: All patients treated for culture-proven keratitis and
      endophthalmitis between January 1, 1995 and December 31, 2009, at the Bascom
      Palmer Eye Institute. METHODS: Ocular microbiology and medical records were
      reviewed on all patients with positive corneal and intraocular cultures over the
      period of the study. Univariate analysis was performed to obtain P values
      described in the study. MAIN OUTCOME MEASURES: Microbial isolates, treatment
      strategies, and visual acuity (VA) outcomes. RESULTS: A total of 9934 corneal
      cultures were performed for suspected infectious keratitis. Only 49 eyes (0.5%)
      progressed to culture-proven endophthalmitis. Fungi (n = 26) were the most common
      responsible organism followed by gram-positive bacteria (n = 13) and gram
      negative bacteria (n = 10). Topical steroid use (37/49 [76%]) was the most common
      associated factor identified in the current study, followed by previous surgery
      (30/49 [61%]), corneal perforation (17/49 [35%]), dry eye (15/49 [31%]), relative
      immune compromise (10/49 [20%]), organic matter trauma (9/49 [18%]), and contact
      lens wear (3/49 [6%]). There were 27 patients in whom a primary infectious
      keratitis developed into endophthalmitis, and 22 patients in whom an infectious
      keratitis adjacent to a previous surgical wound progressed into endophthalmitis.
      Patients in the primary keratitis group were more likely to be male (22/27 [81%]
      vs 8/22 [36%]; P = 0.001), have history of organic matter trauma (8/27 [30%] vs
      1/22 [5%]); P = 0.030), and have fungal etiology (21/27 [78%] vs 5/22 [23%];
      P<0.001). Patients in the surgical wound-associated group were more likely to use
      topical steroids (20/22 [91%] vs 17/27 [63%]; P = 0.024). A VA of >= 20/50 was
      achieved in 7 of 49 patients (14%), but was <5/200 in 34 of 49 (69%) at last
      follow-up. Enucleation or evisceration was performed in 15 of 49 patients (31%).
      CONCLUSIONS: Progression of infectious keratitis to endophthalmitis is relatively
      uncommon. The current study suggests that patients at higher risk for progression
      to endophthalmitis include patients using topical corticosteroids, patients with
      fungal keratitis, patients with corneal perforation, and patients with infectious
      keratitis developing adjacent to a previous surgical wound. Patients with
      sequential keratitis and endophthalmitis have generally poor visual outcomes.
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after
      the references.

PMID- 22858124
TI  - Effect of lutein and zeaxanthin on macular pigment and visual function in
      patients with early age-related macular degeneration.
AB  - PURPOSE: To determine whether supplementation with lutein and zeaxanthin improves
      macular pigment and visual function in patients with early age-related macular
      degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial.
      PARTICIPANTS: Participants with probable AMD who were 50 to 79 years of age were
      screened for study eligibility from the local communities. One hundred eight
      subjects with early AMD were recruited. INTERVENTION: Early AMD patients were
      assigned randomly to receive 10 mg/day lutein (n = 27), 20 mg/day lutein (n =
      27), 10 mg/day lutein plus 10 mg/day zeaxanthin (n = 27); or placebo (n = 27) for
      48 weeks. Macular pigment optical density (MPOD) and visual function variables
      were assessed at baseline, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The
      primary outcome was MPOD. Secondary outcomes were visual function variables
      including best-corrected visual acuity (BCVA), contrast sensitivity (CS),
      photorecovery time, and Amsler grid testing results. RESULTS: Macular pigment
      optical density increased significantly by a mean +/- standard error of 0.076 +/-
      0.022 density unit in the 20-mg lutein group and 0.058 +/- 0.027 density unit in
      the lutein and zeaxanthin group during 48 weeks. There was a significant dose
      response effect for lutein supplementation, and the changes in MPOD from baseline
      to 48 weeks were correlated negatively with baseline MPOD in all active treatment
      groups (r = -0.56; P<0.001). At 48 weeks, a trend toward improvement was seen in
      BCVA, and there was a significant between-group difference in CS at 3 and 6
      cycles/degree between the 20-mg lutein group and the placebo group. The increase
      in MPOD related positively to the reduction in the logarithm of the minimum angle
      of resolution BCVA (r = -0.31; P<0.01) and the increases in CS at 4 spatial
      frequencies (r ranging from 0.26 to 0.38; all P<0.05). CONCLUSIONS: Among
      patients with early AMD, supplementation with lutein and zeaxanthin improved
      macular pigment, which played a causative role in boosting visual function and
      might prevent the progression of AMD. Future studies are required to evaluate the
      effect of these carotenoids on the incidence of late AMD.

PMID- 22858126
TI  - Scleral patch grafts in the management of uveal and ocular surface tumors.
AB  - OBJECTIVE: To evaluate the outcome of scleral patch grafts in a series of
      patients undergoing management for uveal and ocular surface tumors. DESIGN: Case
      series. PARTICIPANTS: Ten patients underwent scleral patch grafting. Five
      patients had uveal melanoma with extrascleral extension, 2 patients had
      scleromalacia secondary to plaque radiotherapy for uveal melanoma, 2 patients had
      suspicious uveoscleral nevi, and 1 patient had invasive conjunctival squamous
      cell carcinoma with scleral necrosis. METHODS: Retrospective, interventional,
      noncomparative chart review of patients undergoing treatment for ocular tumors
      followed by scleral grafts in a tertiary eye care center in the United States
      between September 2003 and January 2011. Sclera was reconstructed with allogenic
      scleral grafts. Clinical observations were performed after grafting. MAIN OUTCOME
      MEASURES: Structural integrity, appearance, and stability of the grafts. RESULTS:
      Ten patients were reviewed. All melanoma cases received plaque radiotherapy with
      palladium 103. The cases with nevi and squamous cell carcinoma underwent local
      resection with cryotherapy as primary treatment. In 8 cases, scleral grafting was
      performed as part of the initial surgery. In all of these cases, satisfactory
      anatomic and functional outcomes were achieved. In 2 cases with scleromalacia
      secondary to radiotherapy for uveal melanoma, grafts were placed several years
      after the initial treatment. In these 2 cases, one showed signs of graft
      retraction, whereas another showed graft thinning. No patients experienced graft
      infection, rejection, or tumor recurrence. CONCLUSIONS: In this series, scleral
      grafts were well accepted when placed as part of the primary tumor management
      despite synchronous radiotherapy, scleral resection, or cryotherapy. Grafting was
      less successful when performed as a late procedure for radiation-induced
      scleromalacia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 22858125
TI  - Change in prostaglandin expression levels and synthesizing activities in dry eye
      disease.
AB  - OBJECTIVE: To investigate the expression level of prostaglandins (PGs) and their
      de novo synthesis in dry eye (DE) disease. DESIGN: Cross-sectional case-control
      study and in vivo mouse experimental study. PARTICIPANTS: Forty-six eyes from 23
      DE patients and 33 eyes from 17 age- and sex-matched controls were studied. Also,
      DE-induced murine eyes were compared with control eyes. METHODS: Patients
      completed a symptom questionnaire using a 100-mm visual analog scale (VAS). Nano
      liquid chromatography tandem mass spectrometry was used for the quantification of
      PGE2 and PGD2. A DE disease environmental chamber was used to induce DE in mice.
      One week after induction, enzyme expressions of cyclooxygenase-1, cyclooxygenase
      2 (COX-2), PG E synthase (PGES), and PG D synthase (PGDS) in the lacrimal glands,
      meibomian glands, and corneas were examined using immunohistochemistry and
      quantitative real-time polymerase chain reaction (qRT-PCR). MAIN OUTCOME
      MEASURES: The mean PGE2 and PGD2 levels in the tears of DE patients were measured
      and compared with symptom severity scores. Immunohistochemistry staining patterns
      and qRT-PCR data of DE mice were quantified. RESULTS: The mean PGE2 level in the
      tears of DE patients (2.72 +/-3 .42 ng/ml) was significantly higher than that in
      the control group (0.88 +/- 0.83 ng/ml; P = 0.003). However, the mean PGD2 level
      in the tears of DE patients (0.11 +/- 0.22 ng/ml) was significantly lower (0.91
      +/- 3.28 ng/ml; P = 0.028). The mean PGE2-to-PGD2 ratio correlated strongly with
      VAS scoring (P = 0.008). In DE mice, COX-2 mRNA was significantly higher in
      ocular surface tissue and lacrimal glands. Furthermore, PGES mRNA was
      significantly higher in ocular surface tissue, whereas PGDS mRNA was decreased.
      Immunohistochemistry staining showed elevated COX-2 expression in the lacrimal
      glands, meibomian glands, corneas, and conjunctivas. Furthermore, PGES expression
      was found in periductal infiltrated cells of the lacrimal glands and conjunctival
      epithelium. Also, PGDS expression was decreased in meibomian glands and increased
      focally in the conjunctival epithelium. CONCLUSIONS: A reciprocal change in PGE2
      and PGD2 levels was found in the tears of DE patients, which correlated with
      patients' symptom scores. These clinical results were supported by increased COX
      2 and PGES expression levels found in tear-producing tissues of DE mice.

PMID- 22858127
TI  - Mycelial fungi completely remediate di(2-ethylhexyl)phthalate, the hazardous
      plasticizer in PVC blood storage bag.
AB  - This pioneering work describes how simply, inexpensively and efficiently novel
      fungi utilize the alarming plasticizer, di(2-ethylhexyl)phthalate (DEHP) blended
      in PVC blood storage bags (BB). In order to quantify total DEHP (33.5%, w/w)
      present in BB, it was extracted using n-hexane and confirmed by GC-MS. Three
      mycelial fungi, viz., Aspergillus parasiticus, Fusarium subglutinans and
      Penicillium funiculosum isolated in our laboratory form heavily plastics
      contaminated soil - either singly or in consortium - completely consumed intact
      DEHP physically bound to BB by static submerged growth (28  degrees C) in simple
      basal salt medium (BSM). A two-stage cultivation strategy was adopted for the
      complete removal of DEHP from BB in situ. During the first growth stage, almost
      70% DEHP contained in the BB was consumed in 2 weeks, accompanied by increased
      fungal biomass (~0.15-0.35 g/g BB; OD ~7 at 600 nm) and a sharp declining (3.3)
      of initial pH (7.2). Spent BSM was replaced at this stagnant growth state (low
      pH), thus in the second stage, remaining DEHP bound to BB utilized completely
      (over 99%). Furthermore, A. parasiticus and F. subglutinans also grew well on
      scrapes of PVC water pipes in BSM. F. subglutinans was as efficient independently
      as consortium in completely utilizing the DEHP bound to BB, and these fungi offer
      great potentials for the inexpensive and eco-friendly bioremediation of
      phthalates in medical and allied PVC wastes on a large scale through a batch
      process in alleviating the plactics waste management issue.

PMID- 22858128
TI  - A novel ion chromatography cycling-column-switching system for the determination
      of low-level chlorate and nitrite in high salt matrices.
AB  - A novel ion chromatography cycling-column-switching system was developed for the
      determination of chlorate and nitrite in high salt matrices. The simple system
      included a pump, two valves, a single eluent, and a conductivity detector. Both
      online pre-concentration and matrix elimination were achieved by this method. The
      target anions were eluted from the concentrator column to the analytical columns
      circularly. Chloride matrix was then eliminated completely. The method was
      applied to the determination of low-level chlorate and nitrite in the chloride
      matrix. Our experimental results demonstrated that this system is of advantages
      such as high sensitivity, facile automation and simple sample pretreatment, which
      might be a promising approach for environmental researches and food control.

PMID- 22858129
TI  - Kinetics and thermodynamics of adsorption for Cd on green manufactured nano
      particles.
AB  - Magnetic nano-particles CuFe(2)O(4) were successful manufactured from industrial
      sludge by combination of acid leaching, chemical exchange, and ferrite process.
      For the first time these recycled nano-particles were used as adsorbent to
      investigate the kinetics and thermodynamics for adsorption of Cd in aqueous
      solutions. These experimental results showed that Cd(2+) adsorption efficiency
      increased from 0.85 to 99.9% when pH increased from 2 to 6. The maximum
      adsorption capacity of Cd(2+) was found to be 17.54 mg g(-1) under the conditions
      at pH 6.0, contact time 30 min, and temperature 318 K. The pseudo-second-order
      kinetic model provides the best correlation with the experimental data compared
      to the pseudo-first-order model. The Langmuir model yields a better fitting than
      the Freundlich model for Cd(2+) adsorption on CuFe(2)O(4) nano-particles under
      investigated temperatures. The thermodynamic constants of the adsorption process
      were evaluated, DeltaG degrees , DeltaH degrees  and DeltaS degrees  is -6.05 kJ
      mol(-1) (at 318 K), 0.71 kJ mol(-1), and 4.53 J mol(-1) K(-1), respectively.
      These results imply that Cd(2+) adsorption onto CuFe(2)O(4) is feasible,
      spontaneous and endothermic in nature.

PMID- 22858130
TI  - Cadmium tolerance and accumulation characteristics of mature flax, cv. Hermes:
      contribution of the basal stem compared to the root.
AB  - The potential of mature flax plants (cv. Hermes) to tolerate and accumulate
      cadmium (Cd) was studied to determine which part of the plant would be the key
      organ for phytoremediation purposes. After 4 month-growth on sand substrate
      containing 0.1mM Cd in a greenhouse, the roots and stems were separated and the
      stems were divided into three parts. The effects of Cd were studied on growth
      parameters, histology and mineral nutrition. No visible toxic symptoms were
      observed. Tolerance-index values calculated from growth parameters and nutrients
      remained relatively high, allowing the development of the plant until maturity
      and formation of seeds. The roots and bottom stem accumulated the highest
      quantity of Cd (750 and 360 mg/kg dry matter), values which largely exceeded the
      threshold defined for hyperaccumulators. On the other hand, basal stem had a high
      bioconcentration factor (BCF=32) and translocation factor TF' (2.5) but a low TF
      (0.5), indicating that this basal part would play a major role in
      phytoremediation (phytostabilization rather than phytorextraction). Therefore,
      the high tolerance to Cd and accumulation capacity make possible to grow Hermes
      flax on Cd-polluted soils.

PMID- 22858131
TI  - Explosion of gaseous ethylene-air mixtures in closed cylindrical vessels with
      central ignition.
AB  - Explosions of gaseous ethylene-air mixtures with various concentrations between
      3.0 and 14.0 vol.% and initial pressures between 0.20 and 1.10 bar were
      experimentally investigated at ambient initial temperature, using several
      elongated cylindrical vessels with length to diameter ratio between 1.0 and 2.4.
      The maximum explosion pressures p(max), the explosion times theta(max), the
      maximum rates of pressure rise, (dp/dt)(max) and the severity factors of
      centrally ignited explosions K(G) are examined in comparison with similar data
      obtained in a spherical vessel. The measured deflagration indices are strongly
      influenced by the length to diameter ratio of the vessels, initial pressure and
      composition of the flammable mixtures. Even when important heat losses are
      present, linear correlations p(max)=f(p(0)) and (dp/dt)(max)=f(p(0)) were found
      for all examined fuel-air mixtures, in all closed vessels. The heat losses
      appearing in the last stage of explosions occurring in asymmetrical vessels were
      estimated from the differences between the experimental and adiabatic maximum
      explosion pressures. These heat losses are higher when the asymmetry ratio L/D is
      higher and were found to depend linearly on the initial pressure.

PMID- 22858132
TI  - [Hip fracture guidelines. A comparison of the main recommendations].
AB  - Hip fracture is the most severe complication of osteoporosis, and despite being a
      frequent health problem, there is a wide variability in both the health care
      provided to these patients and the results achieved after their treatment.
      Clinical guidelines are a tool that helps to reduce this variability. The authors
      of this review try to give a panoramic and comparative view of the key
      recommendations proposed by the main guidelines for the hospital care of hip
      fracture patients. Recommendations on the care in the acute phase are reviewed,
      particularly the initial hospital management, use of tools, preventive measures
      to avoid medical complications, surgery related aspects, treatment of usual
      clinical problems, and shared orthopaedic and geriatric care. Circulating and
      putting into practice the main recommendations will help to improve the health
      care provided to these patients and obtain better outcomes.

PMID- 22858133
TI  - Pre-operative muscle activation patterns during walking are associated with TKA
      tibial implant migration.
AB  - BACKGROUND: Gait biomechanical variables have been associated with total knee
      arthroplasty tibial implant migration measured with Radiostereometric Analysis
      (RSA), but no studies have examined the role of the periarticular musculature,
      which is responsible for a high proportion of the forces on the joint. The
      purpose of this study was to measure the pre-operative electromyography (EMG)
      patterns of the periarticular knee muscles during gait and determine the
      association of these patterns with the post-operative tibial implant migration
      measured with RSA. We hypothesized that pre-operative muscle activation patterns
      (specifically the activation patterns of the vastus and gastrocnemius muscle
      groups) measured with EMG are associated with migration at 6months. METHODS:
      Electromyographic data were collected from 6 periarticular knee joint muscles on
      37 patients pre-operatively during gait. Radiostereometric exams were performed
      immediately and at 6 months post-operatively. Relationships between the pre
      operative patterns of muscle activation and micromotion of the implant were
      examined using Pearson correlation and regression models. FINDINGS: Statistically
      significant correlations were found between the pattern of the quadriceps and
      gastrocnemius muscle activations during gait and implant translation in the
      posterior direction. Regression analysis illustrated that a substantial
      proportion of the variance in the post-operative tibial component posterior
      translation (R2=0.49) was explained by a prolonged activation of the vastus
      medialis muscle and higher activation of the lateral gastrocnemius muscle during
      early stance. INTERPRETATION: The variability in migration explained by the
      muscle activation patterns supports the hypothesis that pre-operative functional
      characteristics can contribute to predicting implant migration following total
      knee arthroplasty surgery.

PMID- 22858134
TI  - Molecular strategies for pre-implantation genetic diagnosis of single gene and
      chromosomal disorders.
AB  - Pre-implantation genetic diagnosis is used to analyse pre-implantation stage
      embryos or oocytes for genetic defects, generally for severe Mendelian disorders
      and chromosome abnormalities. New but controversial indications for pre
      implantation genetic diagnosis include identifying human leukocyte antigen
      compatible embryos suitable as donor, sex selection and adult-onset disorders,
      particularly cancer. Pre-implantation genetic screening is a variant of pre
      implantation genetic diagnosis to improve outcomes of in-vitro fertilisation.
      Array comparative genomic hybridisation is replacing fluorescence in-situ
      hybridisation for aneuploidy screening. Besides technical advancement of array
      platform, the success of pre-implantation genetic screening is strongly related
      to the embryonic biological nature of chromosomal mosaicism. Having been applied
      for more than 20 years, pre-implantation genetic diagnosis is recognised as an
      important alternative to prenatal diagnosis. Diagnosis from a single cell,
      however, remains a technically challenging procedure, and the risk of
      misdiagnosis cannot be eliminated.

PMID- 22858135
TI  - Characterisation of the exopolysaccharide (EPS)-producing Lactobacillus
      paraplantarum BGCG11 and its non-EPS producing derivative strains as potential
      probiotics.
AB  - Traditional fermented foods are the best source for the isolation of strains with
      specific traits to act as functional starters and to keep the biodiversity of the
      culture collections. Besides, these strains could be used in the formulation of
      foods claimed to promote health benefits, i.e. those containing probiotic
      microorganisms. For the rational selection of strains acting as probiotics,
      several in vitro tests have been proposed. In the current study, we have
      characterized the probiotic potential of the strain Lactobacillus paraplantarum
      BGCG11, isolated from a Serbian soft, white, homemade cheese, which is able to
      produce a "ropy" exopolysaccharide (EPS). Three novobiocin derivative strains,
      which have lost the ropy phenotype, were characterized as well in order to
      determine the putative role of the EPS in the probiotic potential. Under
      chemically gastrointestinal conditions, all strains were able to survive around 1
      2% (10(6)-10(7)cfu/ml cultivable bacteria) only when they were included in a food
      matrix (1% skimmed milk). The strains were more resistant to acid conditions than
      to bile salts and gastric or pancreatic enzymes, which could be due to a pre
      adaptation of the parental strain to acidic conditions in the cheese habitat. The
      ropy EPS did not improve the survival of the producing strain. On the contrary,
      the presence of an EPS layer surrounding the strain BGCG11 hindered its adhesion
      to the three epithelial intestinal cell lines tested, since the adhesion of the
      three non-ropy derivatives was higher than the parental one and also than that of
      the reference strain Lactobacillus rhamnosus GG. Aiming to propose a potential
      target application of these strains as probiotics, the cytokine production of
      peripheral blood mononuclear cells (PBMC) was analyzed. The EPS-producing L.
      paraplantarum BGCG11 strain showed an anti-inflammatory or immunosuppressor
      profile whereas the non-ropy derivative strains induced higher pro-inflammatory
      response. In addition, when PBMC were stimulated with increasing concentrations
      of the purified ropy EPS (1, 10 and 100MUg/ml) the cytokine profile was similar
      to that obtained with the EPS-producing lactobacilli, therefore pointing to a
      putative role of this biopolymer in its immune response.

PMID- 22858136
TI  - Regioselective synthesis of fraxinellone-based hydrazone derivatives as
      insecticidal agents.
AB  - In continuation of our program aimed at the discovery and development of natural
      products-based insecticidal agents, twenty-three new fraxinellone-based hydrazone
      derivatives were smoothly prepared from fraxinellone via regioselectively allylic
      oxidation in the presence of selenium dioxide or chromium trioxide under
      microwave irradiation and subsequent condensation with hydrazides or hydrazines.
      Their insecticidal activity was evaluated against the pre-third-instar larvae of
      Mythimna separata Walker in vivo. Especially compounds 6d and 7a displayed the
      most pronounced insecticidal activity compared with toosendanin, a commercial
      botanical insecticide derived from Melia azedarach.

PMID- 22858137
TI  - Urea/thiourea catalyzed, solvent-free synthesis of 5-arylidenethiazolidine-2,4
      diones and 5-arylidene-2-thioxothiazolidin-4-ones.
AB  - An efficient and organo-catalyzed method has been developed for the synthesis of
      5-arylidenethiazolidine-2,4-diones and 5-arylidene-2-thioxothiazolidin-4-ones via
      Knoevenagel condensation of arylaldehydes 1 and 2,4-thiazolidinedione 2a/2
      thioxothiazolidin-4-one 2b under mild conditions. Urea-adduct 4 and azomethine 5
      also afford arylidene-products 3 by reacting with 2a-b via addition-elimination
      reaction. This protocol has the features of use of inexpensive, ecofriendly
      readily available, effective catalyst system viz. urea/thiourea, avoidance of
      volatile solvents, excellent yield and simple work-up procedure.

PMID- 22858138
TI  - DBD dyes as fluorescent probes for sensing lipophilic environments.
AB  - Small fluorescent organic molecules based on [1,3]dioxolo[4,5-f][1,3]benzodioxole
      (DBD) could be used as probes for lipophillic microenvironments in aqueous
      solutions by indicating the critical micelles concentration of detergents and
      staining cell organelles. Their fluorescence lifetime decreases drastically by
      the amount of water in their direct environment. Therefore they are potential
      probes for fluorescence lifetime imaging microscopy (FLIM).

PMID- 22858139
TI  - Combining pharmacophore, docking and substructure search approaches to identify
      and optimize novel B-RafV600E inhibitors.
AB  - In this study for searching novel B-Raf(V600E) inhibitors, pharmacophore-based
      virtual screening identified 1 as a hit bearing 5-benzylidene-2
      thioxodihydropyrimidine-4,6(1H,5H)-dione. Based on 1, scaffold hopping inspired
      by molecular docking discovered 5-(furan-2-ylmethylene)-2-thioxodihydropyrimidine
      4,6(1H,5H)-dione as a new and better scaffold. Substructure search with the new
      scaffold identified 28 active compounds, among which 12 compounds (42.9%) showed
      IC(50) less than 1 MUM. Especially, compound 3o, which is 10-fold more potent
      than the hit 1, is a potent inhibitor comparable to that of the marketed drug
      vemurafenib.

PMID- 22858140
TI  - In vitro evolution of an HIV integrase binding protein from a library of C
      terminal domain gammaS-crystallin variants.
AB  - A protein without natural binding functions was engineered to bind HIV-1
      integrase. Phage display selections applied a library of variants based on the C
      terminal domain of the eye lens protein human gammaS-crystallin. Multiple loop
      regions were altered to encode libraries with ~3.6 * 10(11) different variants. A
      crystallin variant, termed integrase binding protein-10 (IBP-10), inhibits
      integrase catalysis with nanomolar K(i) values. IBP-10 interacts with the
      integrase C-terminal domain and inhibits integrase substrate affinity. This
      allosteric mechanism allows IBP-10 to inhibit drug-resistant integrase variants.
      The results demonstrate the applicability of the crystallin scaffold for the
      discovery of binding partners and enzyme inhibitors.

PMID- 22858141
TI  - Discovery of triazolopyrimidine-based PDE8B inhibitors: exceptionally ligand
      efficient and lipophilic ligand-efficient compounds for the treatment of
      diabetes.
AB  - PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases
      (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput
      screen was run with the goal of identifying selective tools for exploring the
      potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was
      particularly attractive since it was amenable to rapid deconstruction leading to
      inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency
      (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME
      properties ultimately leading to compound 42. This compound was highly potent and
      selective with good bioavailability and advanced into pre-clinical development.

PMID- 22858142
TI  - Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K
      inhibitors free from hERG channel inhibition.
AB  - The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K)
      with good bioavailability in dog is described. The compound was used to
      demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model.
      The margin to hERG ion channel inhibition was deemed too low for a clinical
      candidate and an optimisation program to find isosteres or substitutions on
      benzothiazole group led to the discovery of 20, 24 and 27; all three free from
      hERG inhibition.

PMID- 22858143
TI  - Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV
      replication inhibitors.
AB  - Introduction of a nitrogen atom into the benzene ring of a previously identified
      HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery
      of the more potent pyridothiazole analogues 3. The potency and PK properties of
      the compounds were attenuated by the introductions of various functionalities at
      the R(1), R(2) or R(3) positions of the molecule (compound 3). Inhibitors 38 and
      44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in
      all species studied, and cross genotype activity.

PMID- 22858144
TI  - Synthesis and biological evaluation of novel triazoles and isoxazoles linked 2
      phenyl benzothiazole as potential anticancer agents.
AB  - A new series of isoxazoles and triazoles linked 2-phenyl benzothiazole were
      synthesized and evaluated for their anticancer activity. These compounds have
      been tested for their cytotoxicity three cancer cell lines. Among the compounds
      tested, compound 5d showed good cytotoxicity against Colo-205 and A549 cells in
      comparison to standard control PMX 610(1). Further compound 5d has been tested
      for its apoptotic activity and its inhibitory activity against caspase and PARP
      proteins. Hence this compound has the potential that it can be selected for
      further biological studies.

PMID- 22858145
TI  - Distinct spontaneous shrinkage of a sporadic vestibular schwannoma.
AB  - We present a case with outspoken spontaneous vestibular schwannoma shrinkage and
      review the related literature. The patient was initially diagnosed with a left
      sided, intrameatal vestibular schwannoma, which subsequently grew into the
      cerebello-pontine angle (CPA), followed by total shrinkage of the CPA component
      without any intervention over a 12-year observation period. The literature on
      spontaneous tumor shrinkage was retrieved by searching the subject terms
      "vestibular schwannoma, conservative management" in PubMed/MEDLINE database,
      without a time limit. Of the published data, the articles on "shrinkage" or
      "negative growth" or "regression" or "involution" of the tumor were selected, and
      the contents on the rate, extent and mechanism of spontaneous tumor shrinkage
      were extracted and reviewed. The reported rate of spontaneous shrinkage of
      vestibular schwannoma is 5-10% of patients managed conservatively. Extreme
      shrinkage of the tumor may occur spontaneously.

PMID- 22858146
TI  - Non-radiographic spondyloarthritis: a theoretical concept or a real entity?

PMID- 22858147
TI  - Regulatory B cells play a key role in immune system balance.
AB  - Regulatory B cells (Bregs) may act earlier than regulatory T cells (Tregs) and
      may play as important a role in autoimmune and allergic diseases. Obstacles to
      the investigation of Bregs are the same as those encountered for Tregs: the
      regulatory effects are short-lived in some cases, there is no consistent
      phenotype (C5 expression is neither indispensable nor sufficient), differences
      exist across species (e.g., between humans and mice), and there are a number of
      suppression modalities (IL-10, TGF-beta, expression of proapoptotic membrane
      molecules) that vary across Breg subtypes. The Breg subtypes may be homologous to
      the Treg subtypes (Br1 cells expressing IL-10, Br3 cells expressing TGF-beta, and
      B-Foxp3 cells), although the Br1 subtype seems to predominate. Nevertheless,
      differences with Treg cells may exist: Breg activation may chiefly involve the
      toll-like receptors rather than the antigen receptor; and Bregs act earlier,
      facilitating the recruitment of Tregs then disappearing once the Tregs become
      operational. Bregs make a major contribution to autoimmune disorders associated
      with several forms of immune deficiency, as well as to the absence of transplant
      rejection when there is a strong B cell response. Breg deficiencies have been
      reported in lupus, and the disappointing effects in this disease of treatments
      designed to inhibit the B cell response may be related to further Breg
      impairment. In several animal models, Breg stimulation is effective in correcting
      a variety of autoimmune disorders, most notably those initiated in the mucous
      membranes. Research into the interactions between the gut microbiota and Bregs
      holds considerable promise.

PMID- 22858148
TI  - Isolated rheumatoid arthritis-associated cerebral vasculitis: a diagnostic
      challenge.
AB  - Central nervous system involvement in rheumatoid arthritis is uncommon. In order
      of frequency, published cases have reported rheumatoid nodules, meningeal
      vasculitis, and cerebral vasculitis (CV). The frequency of vasculitic cerebral
      involvement in rheumatoid arthritis is unknown. However, it is known that it is
      more common in patients with seropositive, long-standing rheumatoid arthritis,
      and in those with concomitant systemic vasculitis. We report the case of a 47
      year-old woman with an 11-year history of seropositive rheumatoid arthritis
      without any extra-articular manifestations, with the exception of secondary
      Sjogren's syndrome, presenting with mental status changes and tonic-clonic
      seizures as symptoms of isolated CV. Magnetic resonance imaging (T2) showed
      hyperintense white-matter lesions in the frontal and temporal lobes, as well as
      in the hippocampus and cerebellum. Transcranial Doppler ultrasound findings were
      consistent with CV. Other differential diagnoses were ruled out. The patient
      responded favorably to methylprednisolone and intravenous gammaglobulin therapy.

PMID- 22858149
TI  - Osteomesopyknosis: an incidental discovery due to back pain.

PMID- 22858150
TI  - Effects of modafinil on neural correlates of response inhibition in alcohol
      dependent patients.
AB  - BACKGROUND: Impaired response inhibition is a key feature of patients with
      alcohol dependence. Improving impulse control is a promising target for the
      treatment of alcohol dependence. The pharmacologic agent modafinil enhances
      cognitive control functions in both healthy subjects and in patients with various
      psychiatric disorders. However, very little is known about the underlying neural
      correlates of improvements in response inhibition following modafinil. METHODS:
      We conducted a randomized, double-blind, placebo-controlled, crossover study
      using functional magnetic resonance imaging with a stop signal task to examine
      effects of a single dose of modafinil (200 mg) on response inhibition and
      underlying neural correlates in abstinent alcohol-dependent patients (AD) (n =
      16) and healthy control subjects (n = 16). RESULTS: Within the AD group modafinil
      administration improved response inhibition (reflected by the stop signal
      reaction time [SSRT]) in subjects with initial poor response inhibition, whereas
      response inhibition was diminished in better performing subjects. In AD patients
      with initial poor response inhibition, modafinil-induced SSRT improvement was
      accompanied by greater activation in the thalamus and supplementary motor area
      (SMA) and reduced connectivity between the thalamus and the primary motor cortex.
      In addition, the relationship between baseline response inhibition and modafinil
      induced SSRT improvement was mediated by these changes in thalamus and SMA
      activation. CONCLUSIONS: These findings indicate that modafinil can improve
      response inhibition in alcohol-dependent patients through its effect on thalamus
      and SMA function but only in subjects with poor baseline response inhibition.
      Therefore, baseline levels of response inhibition should be taken into account
      when considering treatment with modafinil in AD.

PMID- 22858152
TI  - Modeling elastic waves in coupled media: Estimate of soft tissue influence and
      application to quantitative ultrasound.
AB  - The effect of medium coupling on propagation of elastic waves is a general
      concern in a variety of engineering and bio-medical applications. Although some
      theories and analytical models are available for describing waves in multi
      layered engineering structures, they do not focus on canvassing ultrasonic waves
      in human bones with coupled soft tissues, where the considerable differences in
      acoustic impedance between bone and soft tissue may pose a challenge in using
      these models (the soft tissues having an acoustic impedance around 80% less than
      that of a typical bone). Without proper treatment of this coupling effect, the
      precision of quantitative ultrasound (QUS) for clinical bone assessment can be
      compromised. The coupling effect of mimicked soft tissues on the first-arriving
      signal (FAS) and second-arriving signal (SAS) in a series of synthesized soft
      tissue-bone phantoms was investigated experimentally and calibrated
      quantitatively. Understanding of the underlying mechanism of the coupling effect
      was supplemented by a dedicated finite element analysis. As revealed, the medium
      coupling impacts influence on different wave modes to different degrees: for FAS
      and SAS, the most significant changes take place when the soft tissues are
      initially introduced, and the decrease in signal peak energy continues with
      increase in the thickness or elastic modulus of the soft tissues, but the changes
      in propagation velocity fluctuate within 5% regardless of further increase in the
      thickness or elastic modulus of the soft tissues. As an application, the
      calibrated effects were employed to enhance the precision of SAS-based QUS when
      used for predicting the simulated healing status of a mimicked bone fracture, to
      find prediction of healing progress of bone fracture based on changes in velocity
      of the FAS or the SAS is inaccurate without taking into account the effect of
      soft tissue coupling, entailing appropriate compensation for the coupling effect.

PMID- 22858151
TI  - Frontal-amygdala connectivity alterations during emotion downregulation in
      bipolar I disorder.
AB  - BACKGROUND: The symptoms of bipolar disorder suggest dysfunction of emotion
      regulatory networks. In healthy control populations, downregulation of emotional
      responses activates the ventral lateral prefrontal cortex (vlPFC) and dampens
      amygdala activation. This study investigated frontal and limbic function and
      connectivity during emotion downregulation in euthymic subjects with bipolar I
      disorder (BPI) and healthy control subjects. METHODS: Thirty BPI and 26 control
      subjects underwent functional magnetic resonance imaging scanning while
      performing an emotion processing task with passive viewing and emotion
      downregulation conditions. Contrasts were made for each group comparing the
      downregulation and passive viewing conditions, and these were entered into a
      between-group random effects analysis to assess group differences in activation.
      Psychophysiological interaction analyses were conducted to test for significant
      group differences in functional connectivity between the amygdala and inhibitory
      frontal regions (i.e., vlPFC). RESULTS: Control subjects showed the expected
      robust bilateral activation of frontal and limbic regions during passive viewing
      and emotion downregulation tasks. Between-group analyses revealed similar
      activation of BPI and control subjects during passive viewing but significantly
      decreased activation in bilateral vlPFC, bilateral anterior and posterior
      cingulate, medial frontal gyrus, and bilateral dorsal lateral prefrontal cortex
      during emotion downregulation in subjects with BPI. Connectivity analysis
      demonstrated that control subjects had significantly greater negative functional
      connectivity between the left amygdala and bilateral vlPFC compared with subjects
      with BPI. CONCLUSIONS: This study provides evidence that dysfunction in the
      neural networks responsible for emotion regulation, including the prefrontal
      cortex, cingulate, and subcortical structures, are present in BPI subjects, even
      while euthymic.

PMID- 22858153
TI  - Alternative nuclear transport for cellular protein quality control.
AB  - Herpesvirus capsids traverse the nuclear envelope (NE) by utilizing an unusual
      export pathway termed nuclear egress. In this process, the viral capsid is
      delivered into the perinuclear space (PNS), producing a vesicular intermediate
      after fission. After fusion with the outer nuclear membrane (ONM), the naked
      capsid is released into the cytosol. A recent study now suggests that this
      pathway might be an endogenous cellular pathway, co-opted by viruses, that serves
      to transport cellular cargo exceeding the size limit imposed by the nuclear pore
      complex (NPC). We propose that one function of this pathway is to transport
      nuclear protein aggregates to the cytosolic autophagy machinery. Our model has
      implications for our understanding of laminopathies and related diseases
      affecting proteins residing at the inner nuclear membrane (INM) and nuclear
      lamina.

PMID- 22858154
TI  - BMI, hypertension and low bone mineral density in adult men and women.
AB  - The aim of this work was to estimate the body mass index (BMI) at which risk of
      hypertension is lowest in men and women, while concurrently considering the
      protective role of adipose tissue in osteoporosis. Healthy, occupationally active
      inhabitants of the city of Wroclaw, Poland, 1218 women and 434 men were studied.
      BMI, systolic and diastolic blood pressures, bone mineral density (BMD) of the
      trabecular compartment and distal radius of the non-dominant hand were recorded.
      Overweight in young women (<=45 years) was associated with increased risk of
      hypertension, whereas the risk of low bone mineral was decreased for the same
      BMI. In older women (>45 years), a BMI>27 was the threshold for increased risk of
      hypertension. In this age group, extremely slim women (BMI<21) had the highest
      risk of low bone mineral density. In younger males (<=45 years), risk of
      hypertension was lowest among the thinnest subjects (BMI<21). Increase in BMI
      over 21 kg/m(2) increased the risk of hypertension. The probability of low bone
      mineral density was the same in all BMI categories of men. In older men (>45
      years), the thinnest (BMI<21) had higher risk of hypertension. To begin from
      BMI=25 kg/m(2), there was a monotonous increase in risk of hypertension in men.
      Higher risk for low bone mineral density was observed in older men with the
      BMI<23. Among younger adults, risk of hypertension and low bone mineral density
      increase at BMI>=21 kg/m(2) in men and BMI>=23 kg/m(2) in women. Among older men
      and women, the BMI threshold was 27 kg/m(2).

PMID- 22858155
TI  - Comments on Soltysiak's paper: "Comment: low dental caries rate in Neandertals:
      the result of diet or the oral flora compositions?".
AB  - A low frequency of dental caries in Neandertal population is still puzzling. Many
      authors stress that the lower frequency of dental caries was related to a meat
      diet. However, a recent publication in HOMO - Journal Comparative Human Biology
      presented a new interpretation of dental caries in Neandertals. In this article,
      Soltysiak supports the thesis that the lower frequency of caries in the
      Neandertal population from the Near East could not be related to the low-sugar
      diet, but rather to the absence of cariogenic bacteria species (S. mutans).
      Although this hypothesis is interesting, I suspect it to be based on several
      erroneous assumptions, and a misunderstanding of caries as a disease. Although he
      stressed that the caries lesion is related to many different factors, in his
      argument he considers one of two alternatives "a low-sugar diet or a lack of
      cariogenic bacterial species".

PMID- 22858157
TI  - Pharmacokinetics, tissue distribution, and the lactone/carboxylate equilibrium of
      hydroxycamptothecin delivered via aerosol in mice.
AB  - Aerosol delivery is a route which is advantageous to the therapy of pulmonary
      diseases, such as lung cancer. The pharmacokinetics and tissue distribution after
      aerosol delivery of carboxylate form of hydroxycamptothecin (C-HCPT) were
      investigated. The concentrations of the three different types (lactone,
      carboxylate and the total of both forms) of HCPT were measured by HPLC analysis.
      The initial experiment showed no evident difference between lactone and
      carboxylate in the lungs during the aerosol treatment, compared with the HCPT
      content in plasma. The AUC(inf) value of lactone in the lungs was higher than
      that of carboxylate, which was 138,176.00 min ng g-1 and 128,460.00 min ng g-1,
      respectively. Meanwhile, AUC(inf) in the plasma during the entire treatment
      indicated that the lactone content was always at a lower level, and the
      carboxylate form tended to predominate, as shown by the lactone/carboxylate (L/C)
      equilibrium. The tissue distribution results showed that the lactone proportion
      in the liver increased up to the maximum value of 69.69% after aerosol
      administration, whereas the mean L/C equilibrium index for the liver was 2.07+/
      1.06, and the C(max) and AUC(0-infinity) values of the total HCPT were highest in
      the tissues. Based on these results we speculated that the initial wholly
      carboxylate form of the HCPT atomized liquid did not influence the transformation
      to lactone form. Moreover, the deposition of the total HCPT and lactone was
      higher in the lungs and other tissues than in the plasma after the aerosol
      treatment. This study will be beneficial to the therapy of pulmonary carcinoma.

PMID- 22858158
TI  - Aqueous ionic liquid based ultrasonic assisted extraction of four acetophenones
      from the Chinese medicinal plant Cynanchum bungei Decne.
AB  - In this study, an aqueous ionic liquid based ultrasonic assisted extraction
      (ILUAE) method for the extraction of the four acetophenones, namely 4
      hydroxyacetophenone (1), 2,5-dihydroxyacetophenone (2), baishouwubenzophenone (3)
      and 2,4-dihydroxyacetophenone (4) from the Chinese medicinal plant Cynanchum
      bungei was developed. Three kinds of aqueous l-alkyl-3-methylimidazolium ionic
      liquids with different anion and alkyl chain were investigated. The results
      indicated that ionic liquids (ILs) showed remarkable effects on the extraction
      efficiency of acetophenones. In addition, the ILUAE, including several ultrasonic
      parameters, such as the ILs concentration, solvent to solid ratio, power,
      particle size, temperature, and extraction time have been optimized. Under these
      optimal conditions (e.g., with 0.6M [C(4)MIM]BF(4), solvent to solid ratio of
      35:1, power of 175 W, particle size of 60-80 mesh, temperature of 25  degrees  C
      and time of 50 min), this approach gained the highest extraction yields of four
      acetophenones 286.15, 21.65, 632.58 and 205.38 MUg/g, respectively. The proposed
      approach has been evaluated by comparison with the conventional heat-reflux
      extraction (HRE) and regular UAE. The results indicated that ILUAE is an
      alternative method for extracting acetophenones from C. bungei.

PMID- 22858156
TI  - Mechanisms of glioma-associated neovascularization.
AB  - Glioblastomas (GBMs), the most common primary brain tumor in adults, are
      characterized by resistance to chemotherapy and radiotherapy. One of the defining
      characteristics of GBM is an abundant and aberrant vasculature. The processes of
      vascular co-option, angiogenesis, and vasculogenesis in gliomas have been
      extensively described. Recently, however, it has become clear that these three
      processes are not the only mechanisms by which neovascularization occurs in
      gliomas. Furthermore, it seems that these processes interact extensively, with
      potential overlap among them. At least five mechanisms by which gliomas achieve
      neovascularization have been described: vascular co-option, angiogenesis,
      vasculogenesis, vascular mimicry, and (the most recently described) glioblastoma
      endothelial cell transdifferentiation. We review these mechanisms in glioma
      neovascularization, with a particular emphasis on the roles of hypoxia and glioma
      stem cells in each process. Although some of these processes are well
      established, others have been identified only recently and will need to be
      further investigated for complete validation. We also review strategies to target
      glioma neovascularization and the development of resistance to these therapeutic
      strategies. Finally, we describe how these complex processes interlink and
      overlap. A thorough understanding of the contributing molecular processes that
      control the five modalities reviewed here should help resolve the treatment
      resistance that characterizes GBMs.

PMID- 22858159
TI  - Epidemiological surveillance of myotonic dystrophy type 1: a 25-year population
      based study.
AB  - This epidemiological study investigates the evolution of the prevalence and the
      phenotypes in a large cohort of myotonic dystrophy type 1 (DM1) patients living
      in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) over a 25-year
      period (1985-2010). In 1985, 406 patients with DM1 were known. From 1985 to 2010,
      352 new DM1 patients were diagnosed and 321 patients died. During this period, we
      observed a significant ageing of the DM1 population, from a median age of
      34.5years to 49.0years. The proportion of patients with an adult phenotype
      decreased significantly from 78% to 53% while the proportion of patients with a
      mild phenotype increased from 6% to 26%. Reasons for the ageing of the DM1
      population and the changes in the distribution of DM1 phenotypes include the
      progressive lowering of total fertility rates over the last decades, a reduction
      of births at risk as a result of genetic counselling and prenatal diagnosis, and
      an increase in the number of mildly affected patients often recognised at an
      older age by predictive testing and molecular analysis. Although the DM1
      prevalence remains very high in 2010 (158/100,000) in the SLSJ region, we observe
      a trend toward a decline in point prevalence rates over the last 10years.

PMID- 22858160
TI  - [Acute otitis media: prevalence of ear pathogens in patients at a public
      hospital].
AB  - BACKGROUND AND OBJECTIVE: Acute otitis media (AOM) is one of the most common
      diseases in childhood and is the most common cause of antibiotic prescriptions in
      children. The gold standard for identifying the pathogens causing AOM is
      tympanocentesis. This is only possible in the stage of AOM when exudate is
      retained in the middle ear. The aim of this study was to describe the prevalence
      of organisms causing AOM in eutrophic patients at a public paediatric hospital.
      MATERIAL AND METHODS: We included all patients with AOM diagnosed by
      otomicroscopy with purulent exudate retained in middle ear and suppurative AOM
      with inadequate drainage consulting at the Otorhinolaryngology Department in a
      paediatric tertiary care centre from 2 May 2009 to 31 August 2010. RESULTS: There
      were 324 patients included in the study, with 180/324 (55.6%) being male. The
      median age was 8 months (interquartile range: 4 to 15 months). Bilateral AOM was
      recorded in 109/324 (33.6%) patients (433 samples for culture were obtained by
      tympanocentesis in 324 patients). At diagnosis, 37% (120/324) of the children had
      been receiving antimicrobial treatment. Of the patients who had received
      antibiotics, 71/120 (59.1%) had bacterial growth in middle ear fluid (MEF)
      cultures, with 51/71 (71.8%) being susceptible to the antibiotic they received;
      20/71 (28.2%) patients were receiving an antibiotic that did not cover the
      spectrum of organisms isolated. CONCLUSION: The pathogens most frequently
      isolated are Streptococcus pneumoniae (39.5%), Haemophilus influenzae (37.4%),
      Moraxella catarrhalis (6.1%) and Streptococcus pyogenes (3.0%).

PMID- 22858161
TI  - Advances in bispecific biotherapeutics for the treatment of cancer.
AB  - Conventional monoclonal antibody (mAb) therapeutics interfering with cellular
      signaling of their respective target antigens are frequently limited in their
      ability to induce significant anti-tumor activities when administered as single
      agents in patients with solid tumors. To overcome these limitations, several new
      technologies are being developed to empower biotherapeutics and to improve their
      anti-tumor activities, while maintaining their high tumor selectivity and
      superior safety profiles. The various efficacy enhancement technologies developed
      for mAbs can be divided broadly into two categories: First, technologies that
      improve the intrinsic anti-tumor activities of conventional immunoglobulin mAb
      formats, including the enhancement of effector cell functions and modulations of
      target binding properties, including interference with multiple signaling
      pathways. The second category of empowered biologics combines complementary anti
      tumor modalities independent of the IgG format, including antibody drug
      conjugates (ADCs). In addition, bispecific compounds designed to recruit
      different subsets of inflammatory cells to the tumor environment, also belong to
      the mechanistic complementation strategy. This approach termed redirected immune
      cell killing, belongs to one the most promising new biotherapeutic platforms
      developed in oncology. Over 20 bispecific compounds are currently being developed
      pre-clinically, and several compounds are undergoing early stage clinical trials.
      In this report, we review the progress made in the development of bispecific
      biotherapeutics in the context of ADCs, redirected T- and B-cell killing and
      targeting of multiple signaling pathways. We also discuss the status of the
      clinical development of this class of compounds in oncology and the promises and
      challenges this field is currently facing.

PMID- 22858162
TI  - Effect of supervised exercise therapy for intermittent claudication in patients
      with diabetes mellitus.
AB  - BACKGROUND: Primary treatment for patients with intermittent claudication is
      exercise therapy. Diabetes mellitus (DM) is a frequently occurring comorbidity in
      patients with intermittent claudication, and in these patients, exercise
      tolerance is decreased. However, there is little literature about the increase in
      walking distance after supervised exercise therapy (SET) in patients with both
      intermittent claudication and DM. The objective of this study was to determine
      the effectiveness of SET for intermittent claudication in patients with DM.
      METHODS: Consecutive patients with intermittent claudication who started SET were
      included. Exclusion criteria were Rutherford stage 4 to 6 and the inability to
      perform the standardized treadmill test. SET was administered according to the
      guidelines of the Royal Dutch Society for Physiotherapy. At baseline and at 1, 3,
      and 6 months of follow-up, a standardized treadmill exercise test was performed.
      The primary outcome measurement was the absolute claudication distance (ACD).
      RESULTS: We included 775 patients, of whom 230 had DM (29.7%). At 6 months of
      follow-up, data of 440 patients were available. Both ACD at baseline and at 6
      months of follow-up were significantly lower in patients with DM (P < 0.001).
      However, increase in ACD after 6 months of SET did not differ significantly (P =
      0.48) between the DM group and the non-DM group (270 m and 400 m, respectively).
      CONCLUSION: In conclusion, SET for patients with intermittent claudication is
      equally effective in improving walking distance for both patients with and
      without DM, although ACD remains lower in patients with DM.

PMID- 22858163
TI  - Anti-GalNAcbeta: a novel anti-glycan autoantibody associated with pregnancy loss
      in women with antiphospholipid syndrome and in a mouse experimental model.
AB  - OBJECTIVES: We evaluated the presence of anti-glycan antibodies (aGA) in patients
      with antiphospholipid syndrome (APS), and associations between aGA and clinical
      features of the disease. METHODS: Sera from APS patients and healthy controls
      were analyzed for aGA levels by ELISA. Analysis of the association of specific
      aGA with clinical manifestations of APS was performed. Selected aGA were affinity
      purified and injected intravenously into naive mice which were tested for fetal
      loss. Matrigel invasion assay was performed for detection of choriocarcinoma
      cells (JAR) invasion and proliferation in the presence of selected aGA. Culture
      fluid of JAR invasion assays was analyzed for the presence of MMP2 and MMP9.
      RESULTS: High levels of several aGA were found in APS sera, of which anti-GalNAc
      beta was significantly associated with recurrent pregnancy loss. Naive mice
      infused intravenously with anti-GalNAc-beta developed increased fetal loss. Anti
      GalNAc-beta significantly inhibited the in-vitro percentage of JAR invasiveness
      and the secretion of MMP2 and MMP9 by human JAR cells. CONCLUSIONS: APS sera
      contain significant levels of aGA directed against several glycans. Anti-GalNAc
      beta Ab is specifically associated with recurrent pregnancy loss both in human
      patients and experimental mouse model. The pathogenic effects of anti-GalNAc-beta
      include inhibition of JAR cells invasiveness accompanied by decreased MMP2 and
      MMP9 secretion.

PMID- 22858164
TI  - Development of a new computer-based physical activity questionnaire to estimate
      habitual physical activity level in Malaysian adolescents.
AB  - OBJECTIVES: To assess the validity and reproducibility of a new computer-based
      physical activity questionnaire (cPAQ) to estimate the habitual physical activity
      levels in Malaysian adolescents. DESIGN: Cross-sectional study. METHODS: About
      425 adolescent boys and girls participated in the study. A heart rate monitor and
      a 7-days physical activity logbook were used as objective and subjective method
      criteria, respectively. RESULTS: The mean estimated weekly total physical
      activity levels measured by the cPAQ were 16.5+/-17.5h and 13.1+/-16.9h for boys
      and girls, respectively. Analyses of the gender-specific Spearman's correlation
      coefficient between cPAQ and both objective and subjective method criteria showed
      that r values ranged from 0.54 to 0.76 (p<0.001). Method comparisons assessed by
      the Bland-Altman plot analysis found that the total physical activity levels,
      calculated from the cPAQ, fell within the mean+/-2 standard deviation.
      Reproducibility of the cPAQ was re-examined after two-weeks, showing that intra
      class correlations for most PA intensity levels in boys and girls were high with
      a mean r value of 0.72. The effectiveness of the cPAQ showed a significantly
      shorter assessment time compared to the manual paper-administered questionnaire
      in adolescents (p<0.001) and the majority of participants (93%) accepted the
      overall appearance of this new cPAQ. CONCLUSIONS: The cPAQ provides a valid and
      reliable method for assessing the habitual physical activity levels for the past
      year in Malaysian adolescents. It was also proven to be highly effective, based
      on duration time and its overall appearance for the adolescent participants.

PMID- 22858165
TI  - Increasing intensity of TENS prevents analgesic tolerance in rats.
AB  - Transcutaneous electrical nerve stimulation (TENS) reduces hyperalgesia and pain.
      Both low-frequency (LF) and high-frequency (HF) TENS, delivered at the same
      intensity (90% motor threshold [MT]) daily, result in analgesic tolerance with
      repeated use by the fifth day of treatment. The current study tested 1) whether
      increasing intensity by 10% per day prevents the development of tolerance to
      repeated TENS; and 2) whether lower intensity TENS (50% MT) produces an
      equivalent reduction in hyperalgesia when compared to 90% MT TENS. Sprague-Dawley
      rats with unilateral knee joint inflammation (3% carrageenan) were separated
      according to the intensity of TENS used: sham, 50% LF, 50% HF, 90% LF, 90% HF,
      and increased intensity by 10% per day (LF and HF). The reduced mechanical
      withdrawal threshold following the induction of inflammation was reversed by
      application of TENS applied at 90% MT intensity and increasing intensity for the
      first 4 days. On the fifth day, the groups that received 90% MT intensity showed
      tolerance. Nevertheless, the group that received an increased intensity on each
      day still showed a reversal of the mechanical withdrawal threshold with TENS.
      These results show that the development of tolerance can be delayed by increasing
      intensity of TENS. PERSPECTIVE: Our results showed that increasing intensity in
      both frequencies of TENS was able to prevent analgesic tolerance. Results from
      this study suggest that increasing intensities could be a clinical method to
      prevent analgesic tolerance and contribute to the effective use of TENS in
      reducing inflammatory pain and future clinical trials.

PMID- 22858166
TI  - The importance of full-time work for urban adults' mental and physical health.
AB  - Unemployment and underemployment have adverse mental and physical health
      consequences, such as increased stress and depression. Health damaging behaviors
      like unhealthy eating, smoking, and alcohol use may be used to cope, contributing
      to chronic disease risk. In this adverse economic climate, it is vital to
      understand the health implications of unemployment and underemployment as well as
      underlying mechanisms. A randomized household survey of adults in six low
      resource communities was conducted in New Haven, Connecticut in 2009, yielding a
      sample of 1205 (73% participation) racially diverse adults (61% Black, 20%
      Latino, 12% White) ages 18-65 (61% women). We used ANOVA to test group
      differences and structural equation modeling to test mediation. 14.5% were
      unemployed and looking for work, 18.4% worked part-time, 38.2% worked full-time.
      Those employed full-time reported the least damaging psychological factors and
      health behaviors: lowest levels of stress and depression, most healthy and least
      unhealthy eating, most physical activity, and lowest levels of smoking and
      drinking. Those employed part-time fell in the middle, and those unemployed fell
      on the unhealthy end of all psychological and behavioral factors. Stress
      significantly mediated the associations of full-time employment with frequency of
      unhealthy eating and physical activity, and amount of cigarette smoking and
      alcohol consumption. Depression significantly mediated the association of full
      time employment with frequency of healthy eating. Compared to <10% nationwide,
      rates of unemployment in this sample were high. Both those unemployed and
      employed part-time reported adverse health behaviors as compared to those
      employed full-time, partially mediated by heightened stress and depression. It is
      vital for the health and well-being of the nation to increase not simply
      employment, but specifically full-time employment. Provision of mental health
      services to those unemployed and underemployed should be a priority to promote
      healthier lifestyles and prevent costly future chronic disease.

PMID- 22858167
TI  - Eye of the beholder? Maternal mental health and the quality of infant sleep.
AB  - Transactional models of parenting and infant sleep call attention to
      bidirectional associations among parenting, the biosocial environment, and infant
      sleep behaviors. Although night waking and bedtime fussing are normative during
      infancy and early childhood, they can be challenging for parents. The current
      study, conducted in the United States between 2003 and 2009, examined concurrent
      and longitudinal associations between maternal mental health and infant sleep
      during the first year. Concurrent associations at 6 and 12 months and
      longitudinal associations from 6 to 12 months were studied in a non-clinic
      referred sample of 171 economically and culturally diverse families. Mothers with
      poorer mental health reported that their infants had more night waking and
      bedtime distress and were more bothered by these sleep issues. Associations
      between infant sleep and maternal mental health were moderated by culture
      (Hispanic/Asian vs. other) and by stressors that included high parenting stress,
      more stressful life events, and low family income. Individual differences in
      maternal well-being may color mothers' interpretations of infants' sleep
      behaviors. It may be prudent to intervene to support maternal mental health when
      infants are referred for sleep problems.

PMID- 22858168
TI  - 20-Hydroxyecdysone attenuates TGF-beta1-induced renal cellular fibrosis in
      proximal tubule cells.
AB  - Renal fibrosis progresses to end stage of diabetes kidney disease, which causes
      irreversible progressive proximal tubular injury. In a previous study, 20
      hydroxyecdysterone (20-HE), a phytoecdysteroid, attenuated renal injury in
      diabetes models. However, the fibrosis regulatory role remains to be
      investigated. METHODS: The proximal tubular epithelial cells (designated as HK-2)
      were treated for 48 h with TGF-beta1 (5 ng/ml) in different concentrations of 20
      HE (0 to 500 nM/ml) in the last 24 h of culture. The extracellular fibronectin
      was measured by ELISA assay. Western blot and immunofluorescence were used to
      evaluate the expression of TGF-beta1/Smads transducer (including Smad2/3, 4, and
      7), epithelial and mesenchymal markers (e.g. E-cadherin and alpha-smooth muscle
      actin) and Snail (transcriptional regulators for EMT). RESULTS: 20-HE reverses
      TGF-beta1-induced increase in fibronectin (both intracellular and extracellular
      fibronectin). Simultaneously, 20-HE reverses TGF-beta1-induced down-regulation of
      Smad7. In addition, 20-HE significantly attenuates TGF-beta1-induced upregulation
      of Smad2/3 and pSmad2/3, and downregulation of E-Cadherin. Moreover, 20-HE
      dramatically suppresses TGF-beta1-induced increases in the expression of Snail.
      CONCLUSION: We propose that 20-HE is a potential fibrosis antagonist for renal
      proximal tubule cells. 20-HE might act through suppressing post-receptor
      signaling of TGF-beta1 and restoring tubule epithelial character by blocking the
      expression of Snail.

PMID- 22858169
TI  - Risk of hospitalization for type 2 diabetes in first- and second-generation
      immigrants in Sweden: a nationwide follow-up study.
AB  - OBJECTIVES: This is the first nationwide study with the aim to analyze whether
      there is an association between country of birth in first-generation immigrants
      and hospitalization for type 2 diabetes (T2D), and to study whether any such
      association remains in second-generation immigrants. DESIGN: In this follow-up
      study, the Swedish Hospital Discharge Register was used to identify all hospital
      diagnoses of T2D in first- and second-generation immigrants in Sweden between
      January 1, 1964 and December 31, 2007. Hospitalization rate ratios standardized
      with regard to gender, age, geographical region, socioeconomic status, obesity,
      and family history of hospitalization for T2D were estimated in first- and second
      generation immigrants. RESULTS: Both increased and decreased risks of
      hospitalization for T2D were shown for several first-generation immigrant groups.
      However, only second-generation immigrants with Finnish or former Yugoslavian
      parents had higher rates of hospitalization for T2D than the reference group. No
      other differences remained in the second-generation immigrants. CONCLUSIONS: The
      present study suggests that ethnic environmental factors may be more important
      than ethnic genetic factors in explaining the observed variation in
      hospitalization for T2D among first-generation immigrants.

PMID- 22858170
TI  - Reported lack of agreement between self-report pain scores in children may be due
      to a too strict criterion for agreement.

PMID- 22858171
TI  - Health and well-being: the role of government.
AB  - This article focuses on the roles that governments take in promoting, protecting
      and enhancing the health and well-being of their populations. It differentiates
      between the policy options available to governments (e.g. legislation, taxation)
      and the key roles that governments carry out using these policy options. Through
      case studies, it provides an insight into the governmental landscape, identifying
      key drivers and levers, and suggesting ways in which progress can be made by
      making links between policy areas.

PMID- 22858172
TI  - Health and work: progress and priorities in 2011.
AB  - This article reflects on the progress that has been made in Britain since
      publication of the Black report on workplace health in 2008. It provides an
      overview of the key recommendations of the report, reflecting on the
      interventions that have been put in place in response to these recommendations by
      the end of September 2011.

PMID- 22858173
TI  - [Evaluation of the Sysmex UF-1000i automated system for the diagnosis of urinary
      tract infection].
AB  - OBJECTIVE: To evaluate the Sysmex UF-1000i system as a urine screening method for
      the diagnosis of urinary tract infection, and epithelial cells as a predictive
      value of contamination in woman of childbearing age. METHODS: A total of 1730
      urine samples were processed using a urine culture as a reference. RESULTS: With
      50 bacteria/MUl as a cut-off point, the results were: sensitivity 91.3%,
      specificity 73.1%, negative predictive value 96.2%. For a specificity of 90% for
      epithelial cells, the results were: sensitivity 31.0%, positive predictive value
      67.0%, negative predictive value 66.0%. CONCLUSION: The evaluated system is fast
      and effective. Epithelial cells could be used to predict contamination.

PMID- 22858174
TI  - Mutations in the West Nile prM protein affect VLP and virion secretion in vitro.
AB  - Mutation of the West Nile virus-like particle (WN VLP) prM protein (T20D, K31A,
      K31V, or K31T) results in undetectable VLP secretion from transformed COS-1
      cells. K31 mutants formed intracellular prM-E heterodimers; however these
      proteins remained in the ER and ER-Golgi intermediary compartments of transfected
      cells. The T20D mutation affected glycosylation, heterodimer formation, and WN
      VLP secretion. When infectious viruses bearing the same mutations were used to
      infect COS-1 cells, K31 mutant viruses exhibited delayed growth and reduced
      infectivity compared to WT virus. Epitope maps of WN VLP and WNV prM were also
      different. These results suggest that while mutations in the prM protein can
      reduce or eliminate secretion of WN VLPs, they have less effect on virus. This
      difference may be due to the quantity of prM in WN VLPs compared to WNV or to
      differences in maturation, structure, and symmetry of these particles.

PMID- 22858175
TI  - Does the reverse shoulder prosthesis medialize the center of rotation in the
      glenohumeral joint?
AB  - Reverse shoulder arthroplasty is commonly used to improve the function of
      osteoarthritic shoulders in cases with irreparable refractory rotator cuff-tear
      arthropathy when conventional prosthesis designs cannot be applied. There is
      indication that moving the glenohumeral joint center more medially may lead to
      improved shoulder function by extending the lever arm for the deltoid muscle and
      facilitating muscle recruitment. However, there is little experimental evidence
      for this medialization effect. Marker based motion data of pre- and one year
      postoperative examinations on nine subjects who underwent reverse shoulder
      arthroplasty were analyzed applying functional methods for joint center
      estimation. The aim was to determine the location of the functional center of
      rotation in the operated and the non-operated contralateral side before and after
      surgery to verify if the joint center of this reverse prosthesis design is
      located more medially compared to the anatomic situation before surgery. It was
      shown that the operated shoulders demonstrated a medialization effect of 8.3+/
      4.3mm. For the non-operated side the difference was 0.1+/-2.3mm, proving the
      accuracy of measurements.

PMID- 22858176
TI  - Evaluation of the absolute bioavailability of pegylated interferon alfa-2a after
      subcutaneous administration to healthy male volunteers: an open-label,
      randomized, parallel-group study.
AB  - BACKGROUND: Interferon (IFN)-based therapy is the recommended treatment for
      hepatitis C virus. Because pegylated IFN (PEG-IFN) alfa-2a is administered
      subcutaneously, it is of interest to determine the proportion of the dose that is
      absorbed from the subcutaneous (SC) tissue and ultimately reaches systemic
      circulation. OBJECTIVE: The goal of this study was to characterize the absolute
      bioavailability of PEG-IFN alfa-2a (40 kDa) after SC dosing (180 MUg) and to
      evaluate the pharmacokinetics of PEG-IFN alfa-2a after intravenous (IV) and SC
      administration. METHODS: In this parallel-group study, 18 participants were given
      a single IV dose of PEG-IFN alfa-2a 90 MUg and 18 participants received PEG-IFN
      alfa-2a 180 MUg SC. Serum concentrations of PEG-IFN alfa-2a were measured predose
      and serially until 312 hours after the first dose. Pharmacokinetic parameters
      (CL/F, volume of distribution, C(max), and T(max)) were estimated using
      noncompartmental methods. Bioavailability was calculated by using the following
      formula: (AUC(SC)/AUC(IV)) . (dose(IV)/dose(SC)). RESULTS: Eighteen healthy males
      received IV PEG-IFN alfa-2a, and an additional 18 healthy males received SC PEG
      IFN alfa-2a. Subjects in each group had comparable mean weight, height, and body
      mass index. After IV administration of PEG-IFN alfa-2a (90 MUg), there was a slow
      decline in serum concentration, the mean rate of systemic clearance was low at
      126 mL/h, and the estimated mean volume of distribution at steady state was 9 L.
      After SC administration of PEG-IFN alfa-2a 180 MUg, absorption was sustained,
      with mean T(max) occurring 102 hours after administration. The mean absolute
      bioavailability was 84%. A higher rate of influenza-like symptoms was observed
      after IV administration, along with decreased neutrophil counts, compared with
      subjects who underwent SC dosing. CONCLUSIONS: Approximately 84% of a SC
      administered dose of PEG-IFN alfa-2a reached the systemic circulation in these
      male healthy volunteers. The slow absorption, restricted distribution, and slow
      elimination of PEG-IFN alfa-2a resulted in sustained serum levels throughout the
      7-day dosing interval.

PMID- 22858177
TI  - Bioavailability and tolerability of combination treatment with revaprazan 200 mg
      + itopride 150 mg: a randomized crossover study in healthy male Korean
      volunteers.
AB  - BACKGROUND: To date, no definitive treatment of functional dyspepsia (FD) has
      been proven to be effective and reasonably well-tolerated. Proton pump inhibitors
      (PPIs) combined with prokinetic agents are considered an effective option.
      Revaprazan is a selective potassium-competitive acid blocker that reversibly
      inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable
      to PPIs. Itopride is a prokinetic agent that has anticholinesterase activity as
      well as dopamine D(2) receptor antagonistic activity. For this reason, revaprazan
      and itopride have been prescribed for FD; however, no available studies have
      reported the pharmacokinetic interactions of these 2 drugs. OBJECTIVE: The
      objective of this study was to compare the bioavailability and tolerability of
      revaprazan and itopride combination therapy to those of equally dosed
      monotherapies to acquire basic drug-drug interaction information about
      revaprazan. METHODS: This multiple-dose, randomized crossover study was conducted
      in healthy male Korean subjects. Subjects received, in randomized sequence, a 7
      day oral dose of revaprazan 200 mg once daily, itopride 50 mg TID, or both. Each
      treatment period was separated by a 7-day washout period. Blood samples were
      collected for up to 24 hours following the last dose at steady state, and drug
      concentrations were determined using validated LC/MS-MS. Pharmacokinetic
      properties were obtained using noncompartmental analysis. Drug tolerability was
      assessed throughout the study, using measurements of vital signs, clinical
      chemistry testing, and interviews. RESULTS: A total of 30 subjects were enrolled
      in the study. Among them, 28 subjects completed revaprazan treatment, and 27
      completed the study (3 subjects were withdrawn). The geometric mean ratios (GMRs)
      (90% CI) of C(max,ss), and AUC(tau,ss) with revaprazan were 0.92 (0.84-1.00) and
      0.96 (0.89-1.03), respectively. The GMRs of C(max,ss) and AUC(tau,ss) with
      itopride were 1.07 (0.96-1.20) and 1.12 (1.06-1.18), respectively. A total of 15
      adverse events (AEs) were reported in 8 subjects. All AEs were considered to be
      mild, and there were no clinically significant differences between treatment
      groups. CONCLUSION: The findings from this study suggest bioequivalence between
      revaprazan given as monotherapy and in combination with itopride in these healthy
      Korean male volunteers, with no clinical significant drug-drug interaction. All
      treatments in this study was generally well tolerated. ClinicalTrials.gov
      identifier: NCT0133289.

PMID- 22858178
TI  - EEG in ischaemic stroke: quantitative EEG can uniquely inform (sub-)acute
      prognoses and clinical management.
AB  - Investigations of (sub-)acute ischaemic stroke (IS) employing quantitative
      electroencephalographic (QEEG) methods, in concert with other assessments, are
      reviewed. Numerous outcomes from hundreds of patients collectively indicate that
      (sub-)acute QEEG indices from standard systems can uniquely inform clinical
      management, particularly prognostication of outcomes from IS. Two classes of QEEG
      indices have proven particularly informative. The first quantifies the power of
      abnormal, slow activity relative to that of faster activity and the second,
      interhemispheric voltage asymmetry (broadband). Both have been identified as
      statistically significant predictors of outcomes assessed (via routine clinical
      scales) in the weeks and months following IS. Furthermore both have demonstrated
      higher predictive value than concomitant neurological assessments and scales, and
      to improve upon outcome prediction afforded by neuroimaging alone. These indices
      also may continuously provide unique, real-time insights into the efficacy of
      thrombolytic therapy, prior to clinical changes. Two key applications of QEEG
      which should prove valuable for future clinical management of IS are: (1)
      continuous, acute monitoring to inform about the efficacy of thrombolysis and
      decisions about potential additional interventions, and; (2) brief, subacute
      recording to inform outcome prognostication and clinical decisions about, for
      example, rehabilitation strategies. Ongoing research and technological
      developments will continue to facilitate clinical translation of QEEG
      investigations reviewed herein.

PMID- 22858179
TI  - Alpha-synuclein aggregates in epicardial fat tissue in living subjects without
      parkinsonism.
AB  - BACKGROUND: In Parkinson's disease (PD), alpha-synuclein (AS) aggregates occur
      frequently in peripheral autonomic nervous system (pANS). Their presence in
      asymptomatic subjects suggests incidental Lewy-body disease (iLBD) that is
      thought to reflect pre-clinical PD. Cardiac involvement has been detected in post
      mortem studies in both, PD and also in iLBD. In vivo documentation of cardiac AS
      pathology is lacking. OBJECTIVE: To prospectively assess the presence of AS
      aggregates in epicardial fat tissue from living subjects without parkinsonism
      undergoing elective cardiac surgery. MATERIAL AND METHODS: Epicardial fat tissue
      obtained during cardiac surgery from 91 subjects was studied by histology and
      immunohistochemistry. Areas more likely to contain pANS elements were selected.
      PD-related motor and non-motor symptoms (NMS) were assessed immediately before or
      after surgery. RESULTS: Small autonomic nerves, ganglia and/or tyrosine
      hydroxylase positive fibres were identified in epicardial fat in each of the 91
      subjects (62 male/29 female, mean age 67 years). AS aggregates were detected in 7
      subjects (7.7%), and were more frequent in those aged above 70 years. In AS
      positive subjects constipation and acting dreams were significantly more frequent
      than in the AS-negative ones. CONCLUSION: AS aggregates occur in epicardial pANS
      in subjects without parkinsonism, suggesting the diagnosis of iLBD. The presence
      in some of these subjects of non-motor symptoms such as acting dreams and
      constipation known to occur in premotor PD supports this interpretation. Adequate
      follow-up of the subjects in this study will indicate the time, if any, to
      progression to motor PD.

PMID- 22858180
TI  - Long-duration Parkinson's disease: role of lateralization of motor features.
AB  - BACKGROUND: A mean of 10 years elapse before patients with Parkinson's disease
      (PD) reach Hoehn & Yahr (H&Y) stage 4, and 14 years for stage 5. A small
      proportion of PD patients survive and are ambulatory for >= 20 years. We sought
      to identify features associated with long-duration PD (dPD). METHODS: This five
      center, case-control study compared 136 PD patients with >= 20 years of duration
      and H&Y stage <= 4 (dPD) to 134 H&Y-, age- and gender-matched PD patients between
      10 and 15 years of disease (cPD). RESULTS: By study design, there were no between
      group differences in age, gender and H&Y. dPD subjects were younger at onset (p <
      0.0001), had more psychosis (p: 0.038), were receiving higher levodopa equivalent
      daily doses (p: 0.02), were predominantly left-handed (p: 0.048), and had greater
      frequency of left-sided onset (p: 0.015) compared to cPD subjects. Both groups
      had similar rates of resting tremor, dementia and REM sleep behavior disorder.
      CONCLUSIONS: Early disease onset, left-handedness and left-sided onset are
      associated with long disease and ambulatory PD survival. The neurobiological
      basis of the prognostic value of lateralization deserves further investigation.

PMID- 22858182
TI  - Exercise stress echocardiographic assessment of outflow tract and ventricular
      function in patients with an obstructed right ventricular-to-pulmonary artery
      conduit after repair of conotruncal heart defects.
AB  - This study assessed right ventricular (RV) and RV outflow tract (RVOT) function
      and pressure in response to exercise in patients with an obstructed RV-pulmonary
      artery (PA) conduit using exercise stress echocardiography (ESE) to evaluate
      these parameters. RV-PA conduits inevitably develop stenosis and/or regurgitation
      over time. Assessment of conduit obstruction only at rest may not reveal the
      extent of physiologic perturbation related to RV pressure loading. Patients with
      a stenotic RV-PA conduit who were being considered for transcatheter pulmonary
      valve placement were approached prospectively. ESE was performed and ventricular
      images were obtained at rest and at peak exercise. Forty patients (median age 17
      years) were enrolled. Most patients had tetralogy of Fallot (63%) and were in New
      York Heart Association class II (59%). Exercise stress echocardiographic images
      were adequate in 38 patients (95%). With exercise there was a significant
      increase in maximum instantaneous RVOT gradient from rest (59 vs 96 mm Hg, p
      <0.001); exercise-induced change in RVOT gradient correlated with global RV
      strain at rest (r = -0.3, p = 0.05). Compared to measurements at rest there were
      significant increases in median peak longitudinal strain of the left ventricular
      free wall, interventricular septum, and global left ventricular strain at peak
      exercise. There were no significant changes in median RV strain at peak exercise
      (RV free wall -14.3 [-26, -8] at rest vs -15.2 [-27, -3] at peak exercise, p =
      0.87; global RV strain -13.9 [-32, -9] vs -15.1 [-23, -6], p = 0.11). In
      conclusion, using ESE it was possible to evaluate abnormal ventricular function
      and conduit dysfunction at peak exercise in patients with an obstructed RV-PA
      conduit.

PMID- 22858181
TI  - Frequency of edema in patients with pulmonary arterial hypertension receiving
      ambrisentan.
AB  - Edema is a common side effect of endothelin receptor antagonists. Ambrisentan is
      an endothelin type A-selective endothelin receptor antagonist approved for the
      treatment of pulmonary arterial hypertension. We examined the clinical outcomes
      of patients who developed edema with and without ambrisentan treatment in 2 phase
      III, randomized placebo-controlled trials, ambrisentan for the treatment of
      pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial
      hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy
      (ARIES) study 1 and 2 (ARIES-1 and ARIES-2) (n = 393). Edema-related adverse
      events were extracted using broad adverse event search terms. The present post
      hoc analysis included 132 placebo patients and 261 ambrisentan patients. Of these
      patients, 14% of the placebo patients and 23% of the ambrisentan patients
      experienced edema-related adverse events. Overall, the patients who experienced
      edema tended to have a worse baseline World Health Organization (WHO) functional
      class (edema 76%, WHO functional class III-IV; no edema 56%, WHO functional class
      III-IV). In the ambrisentan patients, those with edema were older (mean age 58 +/
      13 years) and heavier (mean weight 75 +/- 19 kg) than those without edema (mean
      age 49 +/- 15 years; mean weight 70 +/- 17 kg). At week 12 of treatment, the
      ambrisentan patients had significantly increased their 6-minute walk distance
      (6MWD) by 34.4 m compared to the placebo patients in whom the 6MWD had
      deteriorated by -9.0 m (p <0.001). Among the ambrisentan patients, those without
      edema had a 6MWD increase of 38.9 m and those with edema had a 6MWD increase of
      19.4 m. Ambrisentan significantly improved the brain natriuretic peptide levels
      by -34% compared to the brain natriuretic peptide levels in the placebo group
      that had worsened by +11% (p <0.001). Ambrisentan reduced the brain natriuretic
      peptide concentrations similarly in patients with and without edema. In
      conclusion, the present subanalysis of patients with pulmonary arterial
      hypertension has revealed that ambrisentan therapy provides clinical benefit
      compared to placebo, even in the presence of edema.

PMID- 22858183
TI  - Ambulatory electrocardiogram-based T-wave alternans in patients with vasospastic
      angina during asymptomatic periods.
AB  - T-wave alternans (TWA) is a useful method for evaluating repolarization
      abnormalities and as a predictor of life-threatening ventricular arrhythmias.
      Although life-threatening ventricular arrhythmias are occasionally observed
      during ischemic attacks in patients with vasospastic angina (VSA), there have
      been no studies to detect repolarization abnormalities using TWA analysis in
      these patients during the asymptomatic phase. The aim of this study was to
      analyze modified moving average (MMA) TWA using Holter recordings in 40 patients
      with VSA and in 40 control subjects. The incidence of positive TWA was higher in
      the VSA group than in the control group (24 of 40 [60%] vs 0 of 40 [0%], p
      <0.01). The value of the maximum MMA TWA was also greater in the VSA group than
      in the control group (68.6 +/- 21 vs 34.0 +/- 11 MUV, p <0.01). In the VSA group,
      although there was no significant difference in maximum MMA TWA values between
      patients with multiple- and single-vessel spasm, patients with ventricular
      tachycardias had higher values than those without (83.0 +/- 15 vs 65.9 +/- 20
      MUV, p <0.05). Patients taking calcium channel blockers exhibited decreased
      values of maximum MMA TWA compared with subjects not taking these drugs (73.8 +/-
      18 vs 59.5 +/- 21 MUV, p <0.05). In conclusion, high values and incidences of TWA
      events were observed in patients with VSA. In the VSA group, maximum values of
      MMA TWA were high in patients with ventricular tachycardias but decreased in
      those taking calcium channel blockers. The results suggest that the patients with
      VSA during asymptomatic phases exhibit repolarization abnormalities leading to a
      potential risk for life-threatening arrhythmias.

PMID- 22858184
TI  - High-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and
      cardiovascular disease in United States adults.
AB  - High-density lipoprotein (HDL) cholesterol is inversely associated with the risk
      of cardiovascular disease (CVD). However, whether the protective effect of HDL
      becomes impaired by elevated high-sensitivity C-reactive protein (hs-CRP) is not
      well-established. We evaluated 13,572 United States adults aged >=18 years who
      participated in the cross-sectional National Health and Nutrition Examination
      Survey 1999-2008. The subjects were classified according to the recognized
      cutpoints of HDL cholesterol elevations of >=60 mg/dl, hs-CRP of >3 mg/L, and by
      a history of self-reported coronary heart disease (CHD) or CVD. Multivariate
      logistic regression analysis was used to assess the odds of prevalent CHD and CVD
      according to HDL cholesterol/hs-CRP group, after adjusting for known risk
      factors. Those with HDL cholesterol of >=60 mg/dl and CRP >3 mg/L versus HDL
      cholesterol <60 mg/dl and CRP <=3 mg/L had as high or a greater prevalence of CHD
      (5.5% and 5.3%, respectively) and CVD (8.6% and 6.9%, respectively). Compared to
      those with HDL cholesterol of >=60 mg/dl and CRP <=3 mg/L, those with HDL
      cholesterol >=60 mg/dl and hs-CRP >3 mg/L had a 1.38 (95% confidence interval
      0.94 to 2.02) adjusted odds of CHD and 1.38 (95% confidence interval 1.00 to
      1.90) adjusted odds of CVD. Those with an HDL cholesterol <60 mg/dl and CRP >3
      mg/L had the greatest adjusted odds of both CHD (1.75, 95% confidence interval
      1.28 to 2.38) and CVD (1.74, 95% confidence interval 1.33 to 2.28). In
      conclusion, an hs-CRP >3 mg/L in the presence of HDL cholesterol of >=60 mg/dl is
      associated with an attenuation in the protective association of HDL cholesterol
      >=60 mg/dl and CRP of <=3 mg/L with CHD and CVD.

PMID- 22858185
TI  - Usefulness of the neutrophil-to-lymphocyte ratio to predict bare-metal stent
      restenosis.
AB  - Inflammation plays a crucial role in the pathogenesis of in-stent restenosis
      (ISR). Neutrophil-to-lymphocyte ratio (NLR) provides a simple method for
      assessment of inflammatory status and prognosis in patients with coronary artery
      disease. The aim of the present study was to investigate the predictive value of
      preprocedural NLR on development of ISR in patients undergoing coronary stent
      implantation. We retrospectively analyzed clinical, hematologic, and angiographic
      data of 624 patients (mean age 60.5 +/- 10.2 years, 71.8% men) who had undergone
      coronary stent implantation and a further control coronary angiography owing to
      stable or unstable angina pectoris. Patients were divided into 3 tertiles based
      on preprocedural NLR. Restenosis occurred in 21 patients (10.1%) in the lowest
      tertile, in 62 (29.8%) in the middle tertile, and in 107 (51.4%) in the highest
      NLR tertile (p <0.001). Serum C-reactive protein levels were also significantly
      higher in patients in tertile 3 than in those in tertiles 1 and 2 (p <0.001).
      Using multiple logistic regression analysis, smoking, diabetes mellitus, stent
      length, preprocedural NLR, and C-reactive protein levels emerged as independent
      predictors of ISR. In receiver operating characteristics curve analysis, NLR
      >2.73 had 80% sensitivity and 75% specificity in predicting ISR. In conclusion,
      high preprocedural NLR is a powerful and independent predictor of bare-metal
      stent restenosis in patients with stable and unstable angina pectoris.

PMID- 22858186
TI  - Impact of long-term statin therapy on postprocedural myocardial infarction in
      patients undergoing nonemergency percutaneous coronary intervention.
AB  - Periprocedural statin therapy has been shown to decrease the rate of myocardial
      infarctions (MIs) after percutaneous coronary intervention (PCI). However, the
      impact of long-term statin therapy on postprocedure MI remains unknown. We
      examined the impact of long-term statin therapy on cardiac enzyme (cardiac
      troponin I [cTnI] and creatine kinase-MB [CK-MB]) increases after PCI in patients
      undergoing nonemergency PCI. Using the 2004/2005 Cornell Angioplasty Registry, we
      evaluated 1,482 patients undergoing elective or urgent PCI with normal
      preprocedure cardiac enzymes levels (cTnI and CK-MB). The population was divided
      into 2 groups: (1) patients on long-term (>=7 days) statin therapy before PCI (n
      = 1,073) and (2) patients not on long-term statin regimen (n = 409). Cardiac
      enzyme levels after PCI were assessed at 8, 12, and 18 hours after PCI. An
      increase in cTnI >=1 time upper-limit of normal (ULN) was observed in 830
      patients (56.1%) and an increase in cTnI >=3 times ULN was observed in 518
      patients (35.0%). There was no difference in incidence of cTnI increases >=3
      times ULN in patients on long-term statin therapy versus those not on long-term
      statin therapy in the overall group (35.1% vs 34.5%, p = 0.855). There was a
      trend toward a lower incidence of small cTnI increases >=1 time ULN in patients
      on long-term statin therapy versus those not receiving long-term statins (54.6%
      vs 59.7%, p = 0.090). Incidence of CK-MB increases >=1 time or >=3 times ULN and
      peak cTnI and CK-MB levels were similar between the 2 groups. In a subgroup of
      patients with unstable angina, long-term statin therapy decreased small cTnI
      increases (>=1 time ULN) after PCI (54.6% vs 64.3%, p = 0.023). The greatest
      benefit in decrease of MIs after PCI was seen in patients with unstable angina
      receiving long-term high-dose statin therapy. In conclusion, long-term statin
      therapy did not decrease the incidence of periprocedural MI in patients with
      stable coronary artery disease undergoing nonemergency PCI. In patients with
      unstable coronary syndromes, long-term statin therapy may be beneficial,
      particularly at a high dose.

PMID- 22858187
TI  - Mortality risk associated with bundle branch blocks and related repolarization
      abnormalities (from the Women's Health Initiative [WHI]).
AB  - Electrocardiographic bundle branch block (BBB) has higher cardiac and all-cause
      death. However, reports on the association between BBBs and mortality in the
      general populations are conflicting. The aim of this study was to evaluate the
      risk for coronary heart disease (CHD) and all-cause death associated with left
      BBB (LBBB) and right BBB (RBBB) during 14 years of follow-up in 66,450
      participants from the Women's Health Initiative (WHI) study. Cox proportional
      hazards regression was performed for mortality risk in Women with LBBB (n = 714)
      and those with RBBB (n = 832). In risk models adjusted for demographic and
      clinical risk factors in women with cardiovascular disease (CVD), hazard ratios
      for CHD death were 2.92 (95% confidence interval 2.08 to 4.08, p <0.001) for LBBB
      and 1.62 (95% confidence interval 1.08 to 2.43, p <0.05) for RBBB, and only LBBB
      was a significant predictor of all-cause death (hazard ratio 1.43, 95% confidence
      interval 1.11 to 1.83, p <0.01). In CVD-free women, only LBBB was a significant
      predictor of CHD death (fully adjusted hazard ratio 2.17, 95% confidence interval
      1.37 to 3.43, p <0.01), and neither blocks was predictive of all-cause death.
      From several repolarization variables that were significant mortality predictors
      in univariate risk models, after adjustment for other electrocardiographic
      covariates and risk factors, ST J-point depression in lead aVL <=-30 MUV in women
      with LBBB was an independent predictor of CHD death, with a more than fivefold
      increase in risk. None of the repolarization variables were independent
      predictors in women with RBBB. In conclusion, prevalent LBBB in CVD-free women
      and LBBB and RBBB in women with CVD were significant predictors of CHD death. In
      women with LBBB, ST J-point depression in lead aVL was a strong independent
      predictor of CHD death.

PMID- 22858188
TI  - Safety, effectiveness, and outcomes of cardiac catheterization in nonagenarians.
AB  - With an aging population, nonagenarians (>=90 years of age) are increasingly
      being considered for cardiac catheterization. Because of the paucity of outcomes
      data in this population, we sought to evaluate the acute and intermediate
      outcomes of nonagenarians undergoing cardiac catheterization. A retrospective
      cohort of 44 nonagenarians undergoing 53 cardiac catheterizations from 2002 to
      2010 was identified. Mean age was 91 years (range 90 to 96) with 57% of patients
      being women. Thirteen percent presented with ST-segment elevation myocardial
      infarction, 32% with non-ST-segment elevation myocardial infarction, 14% with
      unstable angina, 25% with chronic angina, and 16% with aortic stenosis. Eighteen
      percent had left main coronary artery disease and 73% had multivessel coronary
      disease. Complications occurred in 6 of 44 patients (3 with acute kidney injury,
      2 with atrial fibrillation, 1 with femoral artery pseudoaneurysm). Twenty
      patients were treated with medical management, 1 patient underwent coronary
      artery bypass surgery, and 2 patients underwent aortic valve replacement. Twenty
      one patients underwent percutaneous coronary intervention in 27 different
      vessels. There was procedural success in 93% of these patients. There were no
      major adverse cardiac events. Five complications occurred after the intervention
      (4 atrial fibrillations, 1 femoral artery pseudoaneurysm). Cumulative mortalities
      at 1 month and 6 and 12 months were 0%, 9%, and 20% respectively. In patients who
      underwent percutaneous coronary intervention or surgery, mortalities were 0%, 0%,
      and 13% at 1 month and 6 and 12 months, respectively.

PMID- 22858189
TI  - Comparison of aortic root diameter to left ventricular outflow diameter versus
      body surface area in patients with marfan syndrome.
AB  - Aortic root dilation is important in the diagnosis of familial aortic syndromes,
      such as Marfan syndrome, and an important risk factor for aortic complications,
      such as dissection or rupture. Transthoracic echocardiography reliably measures
      the absolute aortic root size; however, the degree of abnormality of the
      measurement requires correction for the expected normal aortic root size for each
      patient. The expected normal size is currently predicted according to the body
      surface area (BSA) and age. However, the correlation between root size and BSA is
      imperfect, particularly for older patients. A potential exists to improve the
      diagnosis and treatment of patients with aortic disease, with an improved
      estimation of normal aortic root size. A reference size derived from within the
      cardiovascular system has been hypothesized to provide a more direct correlation
      with the aortic root size. Images from the Stanford echocardiography database
      were reviewed, and measurements of the aortic root and internal dimensions were
      performed in a control cohort (n = 150). The measurements were repeated in adult
      patients with Marfan syndrome (n = 70) on serial echocardiograms (145 total
      studies reviewed). Of the 150 control patients, excellent correlation was found
      between the aortic root and left ventricular outflow tract diameters, r(2) =
      0.67, and r(2) = 0.34 with BSA (p <0.0001, for both). More importantly, using the
      left ventricular outflow tract to predict the normal aortic root size, instead of
      the BSA and age, improved the diagnostic accuracy of aortic root measurements for
      diagnosing Marfan syndrome. In conclusion, an internal cardiovascular reference,
      the left ventricular outflow tract diameter, can improve the diagnosis of aortic
      disease and might provide a better reference for the degree of abnormality.

PMID- 22858190
TI  - Usefulness of albuminuria as predictor for coronary artery stenosis, regardless
      of estimated glomerular filtration rate, in patients with type 2 diabetes
      mellitus.
AB  - The aim of the present study was to evaluate the independent predictors of
      coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and
      subclinical atherosclerosis. A total of 232 patients with type 2 DM and
      subclinical atherosclerosis underwent multislice computed tomography coronary
      angiography. Subclinical atherosclerosis was determined by the carotid intima
      media thickness (IMT) or carotid plaque. Multislice computed tomography coronary
      angiography revealed significant coronary stenosis (>50% in diameter) in 71
      subjects (31%). The subjects who had significant coronary stenosis were much
      older and had had a longer duration of DM. In particular, the log-transformed
      albumin/creatinine ratio (ACR) was greater in the subjects with significant
      coronary stenosis compared to the subjects without significant coronary stenosis.
      The age- and gender-adjusted odds ratio for significant coronary stenosis
      increased in proportion to albuminuria with a given estimated glomerular
      filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95%
      confidence interval 1.497 to 11.599) or categorical variable (ACR >30 MUg/mg,
      odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an
      increased risk of significant coronary stenosis, independent of conventional
      cardiovascular risk factors. In receiver operating characteristic analysis, the
      ACR had an additive effect with carotid IMT for predicting significant coronary
      stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710
      with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of
      albuminuria is an independent predictor for significant coronary stenosis in
      patients with type 2 DM and subclinical atherosclerosis.

PMID- 22858191
TI  - Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity
      and endothelial function: the FAITH randomized clinical trial.
AB  - OBJECTIVE: Aged garlic extract (AGE) is associated with a significant decrease in
      atherosclerotic plaque progression and endothelial function improvement.
      Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial
      function. A stressful lifestyle is a well-known risk factor for the presence and
      progression of atherosclerosis. This study investigated the effect of AGE plus
      CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and
      endothelial function measured by digital thermal monitoring (DTM) in
      firefighters. METHODS: Sixty-five Los-Angeles County firefighters who met the
      eligibility criteria were enrolled in this placebo-controlled, double-blinded
      randomized trial. The firefighters were randomized to four tablets of AGE (300
      mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent
      quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and
      at the 1-year follow-up. RESULTS: There were no significant differences in age,
      cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo
      groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the
      AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for
      cardiovascular risk factors and statin therapy, the mean decrease in vascular
      stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P
      = 0.005). Similarly, the mean increase in the area under the temperature curve,
      the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with
      the placebo group (P = 0.01). CONCLUSION: The combination of AGE and CoQ10 was
      independently associated with significant beneficial effects on vascular
      elasticity and endothelial function in firefighters with high occupational
      stress, highlighting the important role of AGE and CoQ10 in atherosclerotic
      prevention of such individuals.

PMID- 22858192
TI  - Soy isoflavone supplementation could reduce body weight and improve glucose
      metabolism in non-Asian postmenopausal women--a meta-analysis.
AB  - OBJECTIVE: The objective of this study was to conduct a systematic review and a
      meta-analysis to confirm the effects of soy isoflavone supplementation on body
      weight, fasting glucose, and insulin level in non-Asian postmenopausal women.
      METHODS: We searched the PubMed, EMBASE, and Cochrane databases up to October
      2010 for randomized controlled trials regarding the effects of isoflavone
      supplementation on body weight, fasting glucose, and insulin level. Pooled
      estimates and 95% confidence intervals (CIs) were calculated by the fixed-and
      random-effects model. RESULTS: Nine studies with 528 participants for body
      weight, 11 studies with 1182 participants for fasting glucose, and 11 studies
      with 1142 participants for fasting insulin were included, respectively.
      Significant reductions were found in body weight [weighted mean difference (WMD),
      -0.515; 95%CI: -0.895 to -0.134; P = 0.008), glucose level (WMD, -0.189; 95%CI: 
      0.344 to -0.033), and fasting insulin level (WMD, -0.940; 95%CI: -1.721 to 
      0.159) with soy isoflavone supplementation compared with placebo control group in
      non-Asian postmenopausal women after adjusted by unpublished studies.
      Furthermore, isoflavone supplementation in shorter duration (<6 mo) could
      significantly reduce body weight (WMD, -0.506; 95%CI: -0.888 to -0.124; P =
      0.009) and longer duration (>= 6 mo) could significantly reduce blood glucose in
      postmenopausal women (WMD, -0.270; 95%CI: -0.430 to -0.110; P = 0.001).
      Meanwhile, more reduction in body weight was observed in the lower dose subgroup
      (dose < 100 mg). Moreover, it is more effective to reduce body weight and fasting
      insulin level with soy isoflavone supplementation in normal weight (body mass
      index < 30) than obese (body mass index >= 30) women. CONCLUSIONS: This meta
      analysis showed soy isoflavone supplementation could be beneficial for body
      weight reduction, glucose, and insulin control in plasma. Large and well-designed
      studies are recommended to confirm this conclusion.

PMID- 22858193
TI  - Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized
      rats.
AB  - OBJECTIVE: Several studies have shown that soy isoflavones have estrogen-like
      activities and might constitute an alternative to hormone replacement treatment.
      The present study investigated the effects of soy isoflavones alone and combined
      with vitamin D3 on prevention of bone loss. METHODS: Sprague-Dawley rats were
      sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were
      randomly assigned to five groups that were untreated or treated for 14 wk with
      vitamin D3, 17beta-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus
      SIE. The effects of the isoflavones and 1alpha,25(OH)(2)D(3) on cultured
      osteoblasts and osteoclasts also were investigated. RESULTS: In OVX rats, the
      bone mineral density and trabecular bone volume loss were improved by 17beta
      estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more
      effective than vitamin D3 or 17beta-estradiol in inhibiting increases in serum
      tumor necrosis factor-alpha levels and osteoblast osteoprotegerin expression. SIE
      plus vitamin D3 was more effective in increasing osterix expression than each
      alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to
      differentiate into osteoblasts and increased osteoblast mineralization.
      Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased
      osteoclast resorption. The combination of isoflavones plus 1alpha,25(OH)(2)D(3)
      showed additive effects on the increase in cell proliferation of cultured
      preosteoblasts. CONCLUSION: Treatment with soy isoflavones might be an
      alternative to hormone replacement therapy in decreasing bone loss from
      postmenopausal estrogen deficiency. In addition, there are further effects on
      increasing transcription factor osterix expression and preosteoblast
      proliferation when these were combined with vitamin D3.

PMID- 22858194
TI  - The impact of music on metabolism.
AB  - The study of music and medicine is a rapidly growing field that in the past, has
      been largely focused on the use of music as a complementary therapy. Increasing
      interest has been centered on understanding the physiologic mechanisms underlying
      the effects of music and, more recently, the suggested role of music in
      modulating metabolic responses. Research has established a role for music in the
      regulation of the hypothalamic-pituitary axis, the sympathetic nervous system,
      and the immune system, which have key functions in the regulation of metabolism
      and energy balance. More recent findings have shown a role for music in the
      metabolic recovery from stress, the regulation of gastric and intestinal
      motility, the moderation of cancer-related gastrointestinal symptoms, and the
      increase of lipid metabolism and lactic acid clearance during exercise and
      postexercise recovery. The purpose of this article is to summarize the most
      current understanding of the mechanisms by which music affects the metabolic
      responses in the context of potential applications.

PMID- 22858195
TI  - Nonalcoholic fatty liver disease as a pro-resolution defective disorder.

PMID- 22858196
TI  - Therapeutic food benefits after ischemic brain edema.

PMID- 22858197
TI  - Malnutrition screening tools: comparison against two validated nutrition
      assessment methods in older medical inpatients.
AB  - OBJECTIVE: Although several validated nutritional screening tools have been
      developed to "triage" inpatients for malnutrition diagnosis and intervention,
      there continues to be debate in the literature as to which tool/tools clinicians
      should use in practice. This study compared the accuracy of seven validated
      screening tools in older medical inpatients against two validated nutritional
      assessment methods. METHODS: This was a prospective cohort study of medical
      inpatients at least 65 y old. Malnutrition screening was conducted using seven
      tools recommended in evidence-based guidelines. Nutritional status was assessed
      by an accredited practicing dietitian using the Subjective Global Assessment
      (SGA) and the Mini-Nutritional Assessment (MNA). Energy intake was observed on a
      single day during first week of hospitalization. RESULTS: In this sample of 134
      participants (80 +/- 8 y old, 50% women), there was fair agreement between the
      SGA and MNA (kappa = 0.53), with MNA identifying more "at-risk" patients and the
      SGA better identifying existing malnutrition. Most tools were accurate in
      identifying patients with malnutrition as determined by the SGA, in particular
      the Malnutrition Screening Tool and the Nutritional Risk Screening 2002. The MNA
      Short Form was most accurate at identifying nutritional risk according to the
      MNA. No tool accurately predicted patients with inadequate energy intake in the
      hospital. CONCLUSION: Because all tools generally performed well, clinicians
      should consider choosing a screening tool that best aligns with their chosen
      nutritional assessment and is easiest to implement in practice. This study
      confirmed the importance of rescreening and monitoring food intake to allow the
      early identification and prevention of nutritional decline in patients with a
      poor intake during hospitalization.

PMID- 22858198
TI  - Epigenetic consequences of maternal folic acid supplementation on hepatic protein
      expression.

PMID- 22858199
TI  - Characterization of post-hospital infections in adults requiring home parenteral
      nutrition.
AB  - OBJECTIVE: Limited data are available on the incidence and risk factors for
      infection in patients requiring home parenteral nutrition (HPN). METHODS: A
      retrospective study was conducted in 101 consecutive adults (63 female, 38 male)
      discharged on HPN from the Emory University Hospital, Atlanta, GA. New
      bloodstream infections (BSIs) requiring rehospitalization and other infections
      were evaluated. RESULTS: Most infections (75%) developed during the initial 6 mo
      after hospital discharge; rates of BSI were particularly high during the first 4
      mo. Fifty-six patients (55.4%) developed 102 BSIs (11.5 BSIs/1000 catheter-days).
      Most BSIs were attributed to gram-positive organisms (46%), including coagulase
      negative Staphylococcus, Staphylococcus aureus, Enterococcus species, and others,
      followed by Candida species (20%) and gram-negative organisms (13%). Twenty-one
      percent of BSIs were polymicrobial. The BSI incidence rate ratio was
      significantly increased for patients with mean prehospital discharge blood
      glucose concentrations in the highest quartile versus the lowest quartile
      (incidence rate ratio 2.4, P = 0.017). Patients with a peripherally inserted
      central catheter versus non-peripherally inserted central catheter central venous
      catheters had significantly higher rates of BSI (P = 0.018). Thirty-nine patients
      (38.6%) developed 81 non-BSIs, including pneumonia, urinary tract infections, and
      surgical site infections. Postdischarge PN dextrose, lipid, and total calorie
      doses were unrelated to BSI but were variably related to the rate of non-BSIs.
      CONCLUSIONS: Adult patients on HPN exhibit a very high incidence of post-hospital
      infections. Higher mean blood glucose levels during predischarge hospitalization
      and the use of peripherally inserted central catheters at discharge are
      associated with an increased risk of BSI in the postdischarge home setting.

PMID- 22858200
TI  - Angiotensinogen gene polymorphisms and food-intake behavior in young, normal
      female subjects in Japan.
AB  - OBJECTIVE: We examined whether angiotensinogen (AGT) gene polymorphisms are
      associated with food preferences in young, normal female subjects. METHODS: Fifty
      two young, normal female subjects (21-22 y old) were recruited. After a 12-h
      fast, blood samples were obtained to examine the AGT gene polymorphisms (rs699
      and rs7079), angiotensin-converting enzyme (ACE) insertion (I)/deletion (D), and
      adrenergic beta3 receptor (ADRB3) gene polymorphisms (rs4994). A trained
      dietitian interviewed the participants to determine the portion size and
      frequency of food eaten for 1 wk by using the established questionnaire FFQg 3.0.
      RESULTS: The genotypes of the AGT Met235Thr polymorphisms were TT:TC:CC = 2:19:31
      (T:C = 0.22:0.78). The genotypes of AGT rs7079 were CC:CA:AA = 26:21:5 (C:A =
      0.70:0.30), and those of ACE were DD:DI:II = 5:28:19 (D/I = 0.37:0.63). The
      genotypes of ADRB3 Trp64Arg were TT:TC:CC = 38:11:3 (T:C = 0.84:0.16). The total
      caloric intake was greater for those with the MM/MT genotype of AGT Met235Thr
      than for those with the TT genotype (1993 versus 1698 kcal/d, P < 0.05). The
      consumption of total lipids, cholesterol, and unsaturated free fatty acids was
      also higher in those with the MM/MT genotype of AGT Met235Thr than in those with
      the TT genotype. However, the AGT polymorphism (rs7079) and the ACE I/D were not
      associated with food preferences. In contrast, the subjects with ADRB3 Trp64
      tended to show a high energy intake and preferences for proteins and lipids
      including fatty acids and cholesterol. They ate more fish and meat. Multiple
      regression analysis showed that the energy intake in subjects with the MM/MT
      genotype was independently determined by total lipids (B = 11.7, P < 0.0001) and
      carbohydrates (B = 4.6, P < 0.0001). CONCLUSIONS: The AGT Met235Thr polymorphism
      was significantly associated with a higher caloric intake owing to total fat and
      carbohydrate consumption.

PMID- 22858201
TI  - Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin
      signaling and intestinal lipoprotein metabolism of small intestinal enterocytes.
AB  - OBJECTIVE: Increasing evidence suggests that dietary factors may affect the
      expression of multiple genes and signaling pathways, which regulate intestinal
      lipoprotein metabolism. The small intestine is actively involved in the
      regulation of dietary lipid absorption, intracellular transport, and metabolism
      and is closely linked to systemic lipid metabolism. Cinnamon polyphenols have
      been shown to improve glucose, insulin, and lipid metabolism and improve
      inflammation in cell culture, animal, and human studies. However, little is known
      of the effects of an aqueous cinnamon extract (CE) on the regulation of genes and
      signaling pathways related to intestinal metabolism. The aim of the study was to
      investigate the effects of a CE on the primary enterocytes of chow-fed rats.
      METHODS: Freshly isolated intestinal enterocytes were used to investigate
      apolipoprotein-B48 secretion by immunoprecipitation; gene expressions by
      quantitative reverse transcriptase-polymerase chain reaction and the protein and
      phosphorylation levels were evaluated by western blot and flow cytometric
      analyses. RESULTS: Ex vivo, the CE significantly decreased the amount of
      apolipoprotein-B48 secretion into the media, inhibited the mRNA expression of
      genes of the inflammatory cytokines, interleukin-1beta, interleukin-6, and tumor
      necrosis factor-alpha, and induced the expression of the anti-inflammatory gene,
      Zfp36. CE also increased the mRNA expression of genes leading to increased
      insulin sensitivity, including Ir, Irs1, Irs2, Pi3k, and Akt1, and decreased Pten
      expression. CE also inhibited genes associated with increased cholesterol,
      triacylglycerols, and apolipoprotein-B48 levels, including Abcg5, Npc1l1, Cd36,
      Mttp, and Srebp1c, and facilitated Abca1 expression. CE also stimulated the
      phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and
      extracellular-signal-regulated kinase expressions determined by flow cytometry,
      with no changes in protein levels. CONCLUSIONS: These results demonstrate that
      the CE regulates genes associated with insulin sensitivity, inflammation, and
      cholesterol/lipogenesis metabolism and the activity of the mitogen-activated
      protein kinase signal pathway in intestinal lipoprotein metabolism.

PMID- 22858202
TI  - Changes in eating behaviors and body weight in Koreans: the Healthy Twin Study.
AB  - OBJECTIVE: We examined the associations between eating behavior at baseline and
      changes in eating behaviors with weight change, and quantified the contribution
      of eating behavior and genetic effects on weight change. METHODS: A prospective
      study of male (n = 482) and female (n = 879) Korean twins and family members who
      were weighed and assessed twice (baseline visit from December 2005 to December
      2008, follow-up visit 2.7 +/- 0.9 y later) using eating behavior subscales
      (external, emotional, and restrained eating) as measured by the Dutch Eating
      Behavior Questionnaire. RESULTS: After adjusting for family variables, eating
      behavior subscales at baseline, changes in emotional and restrained eating, age,
      education, weight, and lifestyle at baseline, and menopausal status at baseline
      (for women), an increase in external eating was significantly associated with
      weight gain in men (1.08, 95% confidence interval 0.41-1.74) and in women (0.63,
      95% confidence interval 0.13-1.12). None of the three eating behavior subscales
      at baseline or changes in emotional and restrained eating were associated with
      weight change. Eating behavior at baseline and changes in those eating behaviors
      accounted for 4% and 1% of the changes in weight in men and women, respectively.
      Additive genetic effects in women contributed to 18% of weight change, whereas in
      men there was no genetic contribution. CONCLUSIONS: These results suggest that an
      increase in external eating may predict adult weight gain in men and women.
      However, the relative contribution of eating behavior to weight change was very
      small, whereas the contribution of genetic effects on weight change was
      significant in women.

PMID- 22858203
TI  - Fetal programming of dietary fructose and saturated fat on hepatic quercetin
      glucuronidation in rats.
AB  - OBJECTIVE: Phase II biotransformation of flavonoids generates bioactive
      metabolites in vivo. However, data on the effect of environmental and physiologic
      factors and fetal programming on phase II pathways toward flavonoids are limited.
      We examined the effect of parental exposure to a diet high in saturated fats and
      fructose 1 mo before conception through lactation on in vitro hepatic uridine 5'
      diphosphate (UDP)-glucuronosyltransferase (UGT) activity toward quercetin in
      parent and offspring rats and the interaction between diet and sex. METHODS:
      Parents were fed a diet containing 9.9% coconut fat, 0.5% cholesterol, 30%
      fructose, and 30% glucose (SFF) or a control (C) diet containing 11% corn oil and
      60% glucose. After weaning, offspring were fed the C diet for an additional 12
      wk. The glucuronidation rate of microsomal UGT was determined with quercetin 30
      MUmol/L and 12.5 MUg of protein in a total volume of 100 MUL after a 15-min
      incubation at 37 degrees C. Three quercetin glucuronides (7-O-quercetin
      glucuronide, 4'-O-quercetin glucuronide, and 3'-O-quercetin glucuronide) were
      quantified. RESULTS: In the parent females, the SFF diet decreased by 29% and 19%
      the production rate of 3'- and 4'-O-quercetin glucuronide quercetin glucuronides,
      respectively, compared with the C diet (P <= 0.05). The production rate of 7-O
      quercetin glucuronide quercetin glucuronide in the female offspring rats born to
      C dams was 59% larger than in their male counterparts (P < 0.05), but no
      difference was observed in the offspring of SFF dams. CONCLUSION: High dietary
      fructose and saturated fat decreased UGT capacity toward quercetin in female rats
      and in utero exposure to the diet decreased the glucuronidation capacity of their
      pups.

PMID- 22858204
TI  - Effects of heat treatment on structural modification and in vivo antioxidant
      capacity of soy protein.
AB  - OBJECTIVE: The present study identified the effects of heat oxidation on protein
      carbonyl content and alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radical
      scavenging activity in soy protein. The changes on antioxidant status in male
      mice fed a heat-oxidized diet were also investigated. METHODS: Soy protein heated
      at 100 degrees C for 30, 60, and 90 min was used to determine the protein
      carbonyl content and DPPH free radical-scavenging activity in vitro. Male KM mice
      (3 wk old) were fed a normal diet, an oxidized diet (HD) containing 12% heat
      oxidized soy protein, or an HD supplemented with 0.1% lipoic acid. After 4 wk of
      feeding, apparent digestibility, reactive oxygen species, malondialdehyde, and
      total antioxidant capacity levels were measured. The antioxidant enzyme
      activities in serum and tissues were also assayed. RESULTS: Heat-oxidized soy
      protein showed a significant increase in protein carbonyl formation and a
      decrease in DPPH free radical-scavenging activity. The HD induced a significant
      decrease in food intake and apparent digestibility of dry matter and crude
      protein in mice. Increased levels of reactive oxygen species and malondialdehyde
      in serum and tissues accompanied by decreased total antioxidant capacity and
      antioxidant enzyme activities were also observed in HD-fed mice. These changes
      were partly restored in the lipoic acid-treated group. CONCLUSION: Heat-oxidized
      soy protein showed a relatively higher protein carbonyl content and a loss of its
      free radical-scavenging activity in vitro. The heat oxidation also led the soy
      protein to generate reactive oxygen species, decrease the antioxidant status, and
      induce redox imbalance in vivo. The heat oxidation of food protein could be a
      potential health risk in humans.

PMID- 22858205
TI  - Patterns in training, knowledge, and performance of skilled birth attendants
      providing emergency obstetric and newborn care in Afghanistan.
AB  - OBJECTIVE: To assess current skilled birth attendants (SBAs) in Afghanistan,
      looking for opportunities to improve quality and expand emergency obstetric and
      newborn care (EmONC) services. METHODS: The EmONC training, knowledge, and skills
      of 82 doctors and 142 midwives in 78 facilities were assessed using interviews,
      knowledge tests, observation of performance on anatomic models, and decision
      making scenarios. RESULTS: Three-quarters had training in at least half of the 24
      possible skills. Doctors' and midwives' levels of training in specific skills
      were generally similar. Doctors were more likely to be very confident of their
      skills. Midwives and doctors scored similarly in assessments of decision making
      and performance of technical skills. SBAs showed weaknesses in specific steps to
      manage common high-risk emergencies. Decision-making skills were good in a
      maternal care scenario but weak on managing a newborn not breathing. Doctors' and
      midwives' scores were similar. CONCLUSION: Midwives and doctors in Afghanistan
      are similarly competent. Focusing on training and deploying midwives may be cost
      effective without diminishing quality. In-service training and job rotation could
      help SBAs retain their EmONC skills. Training and practice to manage common high
      risk emergencies deserve priority.

PMID- 22858206
TI  - Stable ventricular fibrillation in a heterotopic heart transplant recipient.
AB  - We present an unusual case of ventricular fibrillation in a conscious patient
      symptomatic for chest pain and shortness of breath. Almost 20 years ago he
      underwent heterotopic cardiac transplantation for the treatment of severe
      idiopathic cardiomyopathy. In the precyclosporine era, this technique was
      extremely useful because of the high rate of graft rejection in which the
      maintenance of the native heart could prevent patient death. To date, with the
      improvements in immunosuppressive therapy, it is generally reserved to a specific
      subset of conditions. A coronary angiography and a cardiac MRI confirmed the
      diagnosis. Six months follow-up ECG was unchanged suggesting the persistence of a
      double heart rhythm in the same body.

PMID- 22858207
TI  - Reasons for suicide attempts in a clinical sample of active duty soldiers.
AB  - BACKGROUND: Self-reported reasons for suicide attempts were examined in a sample
      of active duty soldiers who had attempted suicide using a functional approach
      that classifies suicidal behaviors into four primary functions of reinforcement:
      automatic negative (AN-R; to reduce aversive internal experiences), automatic
      positive (AP-R; to generate desired internal experiences), social negative (SN-R;
      to avoid aversive contextual demands), and social positive (SP-R; to generate
      desired environmental contexts). Based on previous theory and research, the
      authors hypothesized that soldiers would attempt suicide primarily to reduce
      aversive internal experiences (i.e., AN-R). METHODS: 72 soldiers (66 male, 6
      female; 65.3% Caucasian, 9.7% African-American, 2.8% Asian, 2.8% Pacific
      Islander, 4.2% Native American, and 9.7% "other"; age M=27.34, SD=6.50) were
      interviewed using the Suicide Attempt Self Injury Interview to assess suicidal
      intent, method, lethality, and reasons for attempting suicide. RESULTS: Soldiers
      endorsed attempting suicide for both automatic and social reasons, with multiple
      functions being endorsed in 95% of attempts. AN-R was endorsed in 100% of suicide
      attempts, and was primary to other functions. Suicidal intent was weakly
      correlated with AN-R, AP-R, and SN-R functions (rs<.22), and medical lethality
      was very weakly correlated with only the SP-R function (r=.18). LIMITATIONS:
      Small sample size and retrospective self-report methodology. CONCLUSIONS:
      Soldiers attempt suicide primarily to alleviate emotional distress. Reasons for
      attempting suicide do not correlate strongly with suicidal intent or medical
      lethality.

PMID- 22858208
TI  - Do alcohol use disorders destabilize the course of bipolar disorder?
AB  - OBJECTIVES: To determine whether long-term data implicate a negative effect of
      alcohol-use disorders (AUDs) on time to remission, risk of mood episode
      recurrence, and risk of mood switch/cycling in patients with bipolar disorder
      (BD). The short-term temporal sequence between alcohol use and onset of mood
      episodes was also examined. METHODS: A MEDLINE literature search was conducted
      for measurement-based reports of alcohol and course of bipolar disorder. RESULTS:
      Twenty-three original data publications were identified. Three out of 5 studies
      addressing the impact of AUDs on recovery from a mood episode demonstrated that
      alcohol did not prolong index mood episodes of any type. Six out of 11 reports
      evaluating the relationship between alcohol and the long term risk of mood
      episode recurrences suggested that high levels of alcohol intake increase the
      risk of a mood recurrence. Five out of 7 studies evaluating the short-term
      temporal sequence of AUDs and development of mood episodes among BD patients
      found that increased alcohol use preceded the development of new mood episodes.
      Four out of 5 studies examining the association between alcohol and rapid cycling
      indicated that AUDs were associated with higher rates of rapid-cycling.
      LIMITATIONS: We limited our review to studies that were large enough to perform
      statistical testing, which may have led us to overlook informative smaller
      studies. CONCLUSIONS: Although alcohol does not seem to affect time to mood
      episode remission, alcohol use destabilizes the course of illness over the long
      run as evidenced by associations with more rapid cycling and mood episode
      recurrence.

PMID- 22858209
TI  - Multivariate analysis of bipolar mania: retrospectively assessed structure of
      bipolar I manic and mixed episodes in randomized clinical trial participants.
AB  - BACKGROUND: Manic episodes are heterogeneous. Mixed states may differ in
      important clinical characteristics from other manic episodes. However, it has not
      been established whether mixed states are a distinct type of episodes, or a
      common basic structure exists across manic episodes. METHODS: Using 2179 well
      characterized subjects in the pretreatment phase of six randomized, clinical
      trials, we conducted rotated factor analysis followed by cluster analysis, using
      all items from the Young Mania Rating Scale and the Montgomery-Asberg Depression
      Scale. Analyses were conducted for all subjects (n=2179) and for those in
      Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV)
      mixed (n=644) and non-mixed (n=1535) episodes separately. RESULTS: There were
      five factors characterized (in order of variance accounted for) as depression,
      mania, sleep disturbance, judgment/impulsivity and irritability/hostility.
      Cluster analysis identified five clusters. Three were predominately manic, with
      depression scores below average for the overall group. Two had high average
      depression scores; these clusters differed in irritability/hostility.
      Judgment/impulsivity scores were similar across factors. Essentially identical
      factors and clusters existed whether analyses were done in all subjects or only
      in subjects classified by DSM-IV as mixed or non-mixed. LIMITATIONS: Exclusion
      criteria of studies may limit generalizability of findings. DISCUSSION: All manic
      episodes, whether mixed or non-mixed, shared a similar structure according to
      factor/cluster analysis. Patients with high depression factor scores were
      heterogeneous with respect to irritability. These data suggest that depressive
      symptoms should be considered a dimensional property across manic episodes,
      rather than as defining a specific type of episode.

PMID- 22858211
TI  - Early vs. conventional switching of antidepressants in patients with MDD and
      moderate to severe pain: a double-blind randomized study.
AB  - BACKGROUND: Concomitant painful physical symptoms in depressive patients
      frequently impair functioning and failure to treat these symptoms may adversely
      impact treatment outcomes of depression. Early vs. conventional switch of
      antidepressants were compared in patients with major depressive disorder (MDD)
      and moderate to severe pain. METHOD: Pre-specified subgroup analysis of a 16
      week, randomized, double-blind clinical study on MDD patients with >30 mm overall
      pain visual analog scale (VAS). Patients not achieving 30% reduction Hamilton
      Depression Rating Scale (HAM-D) after 4 weeks escitalopram (10 mg/day) were
      randomized to duloxetine 60-120 mg/day (early switch) or continued on
      escitalopram (conventional switch) with non-responders at week 8 switching to
      duloxetine. Endpoints were time to confirmed response and remission, VAS pain
      severity, and Sheehan disability scale (SDS). Switch strategies were compared
      using Kaplan-Meier, logistic regression, and repeated measures analyses. RESULTS:
      No differences between early and conventional switching were found in time to
      confirmed response after randomization (3.9 vs. 4.1 weeks, p=0.511) or remission
      (6.0 vs. 8.0 weeks, p=0.238). Significantly lower VAS mean pain levels at for
      overall pain, headache, back pain, shoulder pain, interference with daily
      activities, and time being awake in pain were found for patients in the early
      switching group. Time to achieving normal functioning (SDS total score <6) was
      shorter in the early switching group (p=0.042). Safety results were comparable
      between switch strategies. CONCLUSIONS: In MDD patients with moderate to severe
      painful physical symptoms not improving after 4 weeks of treatment with
      escitalopram, an earlier switch to duloxetine may lead to better pain and
      functional outcomes.

PMID- 22858210
TI  - Cortisol responses to psychosocial stress predict depression trajectories: social
      evaluative threat and prior depressive episodes as moderators.
AB  - BACKGROUND: Alterations of hypothalamic-pituitary-adrenal (HPA) function are well
      established in adults with current depression. HPA alterations may persist into
      remission and confer increased risk for recurrence. METHODS: A modified version
      of the Trier Social Stress Test (TSST) was administered at baseline to 32 young
      adults with remitted major depressive disorder and 36 never-depressed controls.
      Participants were randomly assigned to either a 'high-stress' condition involving
      social evaluation or a 'low-stress' control condition. Cortisol concentrations
      were measured in saliva samples throughout the TSST. Participants were assessed
      again after 6 months for the occurrence of stressful life events and depressive
      symptoms/disorders during the follow-up period. RESULTS: Participants who
      exhibited enhanced cortisol reactivity in the low-stress condition showed
      increases in depressive symptoms over follow-up, after controlling for stressful
      life events during the follow-up period. Anticipatory stress cortisol and
      cortisol reactivity each interacted with history of depressive episodes to
      predict depression trajectories. LIMITATIONS: The single TSST administration
      limits conclusions about whether alterations of cortisol reactivity represent
      trait-like vulnerability factors or consequences ("scars') of past depression.
      CONCLUSIONS: These results extend previous findings on stress sensitivity in
      depression and suggest that altered HPA function during remission could reflect
      an endophenotype for vulnerability to depression recurrence. Findings support
      interactive models of risk for depression recurrence implicating HPA function,
      depression history, and sensitivity to minor stressors. Results may have
      implications for interventions that match treatment approaches to profiles of HPA
      function.

PMID- 22858212
TI  - Randomized sham controlled trial of repetitive transcranial magnetic stimulation
      to the dorsolateral prefrontal cortex for the treatment of panic disorder with
      comorbid major depression.
AB  - BACKGROUND: In an open-label trial low-frequency repetitive transcranial magnetic
      stimulation (rTMS) to the right dorsolateral prefrontal cortex (DLPFC)
      significantly improved symptoms of panic disorder and major depression. Here we
      present data of a randomized double-blind study. METHODS: Twenty-five patients
      were assigned 4 weeks of active or sham rTMS to the right DLPFC. rTMS parameters
      consisted of 1800 stimuli/day, 1-Hz, at 110% of resting motor threshold. Response
      was defined as a >=40% decrease on the panic disorder severity scale and a >=50%
      decrease on the Hamilton depression rating scale. At the end of the randomized
      phase, patients were offered the option of receiving open-label rTMS for an
      additional 4 weeks. RESULTS: Repeated-measures ANOVA revealed significantly
      better improvement in panic symptoms with active compared with sham rTMS, but no
      significant difference in depression. At 4 weeks, response rate for panic
      disorder was 50% with active rTMS and 8% with sham. After 8 weeks of active rTMS,
      response rate was 67% for panic and 50% for depressive symptoms. Repeated-measure
      ANOVA showed significant improvements in panic disorder, major depression,
      clinical global impression, and social adjustment. Clinical improvement was
      sustained at 6-month follow-up. LIMITATIONS: Limitation of this study is the
      relatively small sample size. CONCLUSIONS: Although 4 weeks of rTMS was
      sufficient to produce a significant effect in panic symptoms, a longer course of
      treatment resulted in better outcomes for both panic disorder and major
      depression. These data suggest that inhibitory rTMS to the right DLPFC affects
      symptoms expression in comorbid anxiety and depression. ClinicalTrials.gov
      Identifier: NCT00521352.

PMID- 22858213
TI  - Reduced posterior corpus callosum area in suicidal and non-suicidal patients with
      bipolar disorder.
AB  - BACKGROUND: Impulsivity is a characteristic of bipolar disorder (BD) that can
      contribute to the risk for suicidal behavior. Evidence suggests that gray and
      white matter abnormalities are linked with impulsivity, but little is known about
      the association between corpus callosum (CC) and impulsivity in BD. We examined
      the CC area and impulsivity in euthymic bipolar I patients, with and without
      lifetime history of suicide attempts, and in healthy controls. METHODS: Nineteen
      bipolar patients with a suicide attempt history (BP-S), 21 bipolar patients
      without suicide attempt history (BP-NS), and 22 healthy controls (HC) underwent
      clinical assessment by the Structured Clinical Interview with the DSM-IV axis I
      (SCID-I), the Barratt Impulsiveness Scale (BIS-11), and MRI scan. RESULTS: No
      differences were observed for any CC subregion between BP-S and BP-NS groups.
      There was a significant reduction in the genu (p=0.04) and isthmus areas
      (p=0.01), in bipolar patients compared with HC. In the BP-S group, the BIS-11
      total (p=0.01), attention (p=0.001) and non-planning (p=0.02) impulsivity scores
      were significantly higher than in the BP-NS and HC groups. LIMITATIONS: These
      results cannot establish causality because of the cross-sectional nature of the
      study. CONCLUSION: This report potentially provides evidence that a reduction in
      the CC area is present even in non-symptomatic bipolar patients, which may be
      evidence of a biological trait marker for BD. Furthermore, the study demonstrated
      that BP-S group had higher impulsivity even during euthymia, which points to a
      sustained association between lifetime history of suicide attempts and
      impulsivity in BD.

PMID- 22858214
TI  - Social phobia in obsessive-compulsive disorder: prevalence and correlates.
AB  - BACKGROUND: Social Phobia (SP) is an anxiety disorder that frequently co-occurs
      with obsessive-compulsive disorder (OCD); however, studies that evaluate clinical
      factors associated with this specific comorbidity are rare. The aim was to
      estimate the prevalence of SP in a large multicenter sample of OCD patients and
      compare the characteristics of individuals with and without SP. METHOD: A cross
      sectional study with 1001 patients of the Brazilian Research Consortium on
      Obsessive-Compulsive Spectrum Disorders using several assessment instruments,
      including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the
      Structured Clinical Interview for DSM-IV Axis I Disorders. Univariate analyses
      were followed by logistic regression. RESULTS: Lifetime prevalence of SP was
      34.6% (N=346). The following variables remained associated with SP comorbidity
      after logistic regression: male sex, lower socioeconomic status, body dysmorphic
      disorder, specific phobia, dysthymia, generalized anxiety disorder, agoraphobia,
      Tourette syndrome and binge eating disorder. LIMITATIONS: The cross-sectional
      design does not permit the inference of causal relationships; some retrospective
      information may have been subject to recall bias; all patients were being treated
      in tertiary services, therefore generalization of the results to other samples of
      OCD sufferers should be cautious. Despite the large sample size, some hypotheses
      may not have been confirmed due to the small number of cases with these
      characteristics (type 2 error). CONCLUSION: SP is frequent among OCD patients and
      co-occurs with other disorders that have common phenomenological features. These
      findings have important implications for clinical practice, indicating the need
      for broader treatment approaches for individuals with this profile.

PMID- 22858215
TI  - Effects of adjunctive peer support on perceptions of illness control and
      understanding in an online psychoeducation program for bipolar disorder: a
      randomised controlled trial.
AB  - OBJECTIVES: To examine the comparative effectiveness of an online psychoeducation
      program for people diagnosed with bipolar disorder within the previous 12 months,
      completed alone or with adjunctive peer support, on symptoms and perceived
      control over the illness. METHOD: Participants were randomly allocated to an
      eight-week online psychoeducation program (n=139), a psychoeducation program plus
      online peer support (n=134) or an attentional control condition (n=134). RESULTS:
      Increased perceptions of control, decreased perceptions of stigmatisation and
      significant improvements in levels of anxiety and depression, from pre- to post
      intervention were found across all groups. There were no significant differences
      between groups on outcome measures, although a small clinical difference was
      found between the supported and unsupported conditions in depression symptoms and
      in functional impairment at the six-month follow-up. Adherence to the treatment
      program was significantly higher in the supported intervention than in the
      unsupported program. Gender and age were also significant predictors of
      adherence, with females and those over the age of 30 showing greater adherence.
      LIMITATIONS: Mood state at study entry was measured by self-report rather than by
      clinical interview. CONCLUSIONS: The pattern of outcomes suggests a primary
      influence of non-specific or common therapeutic factors across all three
      intervention groups. A personally tailored intervention may be more suitable for
      individuals recently diagnosed with bipolar disorder, and longer term coaching
      may increase program adherence and long-term improvement in symptoms and
      functioning.

PMID- 22858216
TI  - Is comorbid borderline personality disorder in patients with major depressive
      episode and bipolarity a developmental subtype? Findings from the international
      BRIDGE study.
AB  - BACKGROUND: The nature of the relationship between bipolar disorder (BD) and
      borderline personality disorder (BPD) is controversial. The aim of this study was
      to characterize the clinical profile of patients with BD and comorbid BPD in a
      world-wide sample selected during a major depressive episode (MDE). METHODS: From
      a general sample of 5635 in and out-patients with an MDE, who were enrolled in
      the multicenter, multinational, transcultural BRIDGE study, we identified 2658
      subjects who met bipolarity specifier criteria. Bipolar specifier patients with
      (BPD+) and without (BPD-) comorbid BPD were compared on diagnostic, socio
      demographic, familial and clinical characteristics. RESULTS: 386 patients (14.5%)
      met criteria for BPD. A diagnosis of BD according to DSM-IV criteria was
      significantly more frequent in the BPD- than in BPD+, while similar rates in the
      two groups occurred using DSM-IV-Modified criteria. A subset of the BD criteria
      with an atypical connotation, such as irritability, mood instability and
      reactivity to drugs were significantly associated withthe presence of BPD. BPD+
      patients were significantly younger than BPD- bipolar patients for age, age at
      onset of first psychiatric symptoms and age at first diagnosis of depression.
      They also reported significantly more comorbid Alcohol and Substance abuse,
      Anxiety disorders, Eating Disorder and Attention Deficit Hyperactivity Disorder.
      In comparison with BPD-, BPD+ patients showed significantly more psychotic
      symptoms, history of suicide attempts, mixed states, mood reactivity, atypical
      features, seasonality of mood episodes, antidepressants induced mood lability and
      irritability, and resistance to antidepressant treatments. LIMITATIONS: Centers
      were selected for their strong mood disorder clinical programs, recall bias is
      possible with a cross-sectional design, and participating psychiatrists received
      limited training. CONCLUSIONS: We confirm in a large sample of BD patients with
      MDE the high prevalence of patients who meet DSM-IV criteria for BPD. Further
      prospective researches should clarify whether the mood reactivity and instability
      captured by BPD DSM-IV criteria are distinguishable from the subjective mood of
      an instable, dysphoric, irritable manic/hypomanic/mixed state or simply represent
      a phenotypic variant of BD, related to developmental factors.

PMID- 22858217
TI  - Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients
      during bipolar depression.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an enzyme implicated in a
      number of pathological conditions such as cardiovascular disease, cancer, and
      neuropsychiatric disorders. Increased blood levels of MMP-9 were found in cancer,
      heart disease and migraine. Molecular-genetic studies demonstrated an association
      of functional polymorphism of MMP-9 gene with predisposition to schizophrenia and
      bipolar illness. In this first study of serum MMP-9 in psychiatric illness, we
      estimated it in patients with bipolar mood disorder both during depression or
      mania as well as during immediate remission after these episodes. METHODS: The
      study was performed on 54 in-patients with bipolar mood disorder (19 males, 35
      females), aged 42+/-14 years. Thirty were studied during acute episode and
      immediate remission after depression, and 24 during acute episode and immediate
      remission after mania. The control group consisted of 29 subjects (15 males, 14
      females) aged 40+/-11 years. Serum MMP-9 was estimated by ELISA. RESULTS: In
      patients with bipolar illness, a significant correlation of MMP-9 levels was
      obtained with age. Younger patients with depression (below or equal 45 years of
      age), both during acute episode and in remission after depression had
      significantly higher MMP-9 levels compared to those with acute episode and
      remission after mania and control subjects. LIMITATIONS: Relatively small number
      of patients, who were receiving different antidepressant, antipsychotic and mood
      stabilizing drugs that might have influenced MMP-9 levels. CONCLUSIONS: Increased
      levels of serum MMP-9 during depression in young patients may indicate this
      phenomenon as a possible biochemical marker for staging of bipolar disorder.

PMID- 22858218
TI  - Depression, anxiety and cardiovascular disease: which symptoms are associated
      with increased risk in community dwelling older adults?
AB  - BACKGROUND: Depression is a risk factor for Cardiovascular Disease (CVD). It has
      been reported that somatic symptoms of depression and not cognitive symptoms are
      associated with increased risk although findings have been inconsistent. Few
      studies have examined whether co-morbid anxiety confers additive risk. METHODS:
      We conducted a cross sectional analysis of 7872 community dwelling adults aged 50
      years and over from The Irish LongituDinal Study on Ageing (TILDA). Depressive
      and anxiety symptoms were assessed with Center for Epidemiologic Studies
      Depression (CES-D) scale and the anxiety subscale of the Hospital Anxiety and
      Depression Scale (HADS-A), respectively. We conducted logistic regression
      analyses to determine the relationship between depression, anxiety, individual
      depressive symptoms and CVD. We further determined whether co-morbid anxiety was
      associated with increased risk. RESULTS: Seven hundred and thirty eight (9.4%)
      study participants reported clinically significant depression. Depression was
      associated with 80% increased risk of CVD following adjustment for cardiovascular
      risk factors. Individual depressive symptoms most consistently associated with
      CVD included low mood, sadness, amotivation, fatigue, diminished appetite and
      concentration difficulties. Anxiety was associated with increased risk of CVD but
      did not confer additive risk in participants with depression. LIMITATIONS: Cross
      sectional design. CONCLUSION: Core symptoms of depression, which are both
      cognitive and somatic in nature, are associated with increased risk of CVD while
      co-morbid anxiety did not confer additive risk. It is important that clinicians
      give due regard both to both cognitive and somatic symptoms of depression when
      determining cardiovascular risk. Future longitudinal investigation should confirm
      these findings and explore potential pathological mechanisms.

PMID- 22858219
TI  - Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a
      randomised controlled trial.
AB  - BACKGROUND: Preliminary evidence suggests that the use of ketamine during
      electroconvulsive therapy (ECT) may be neuroprotective against cognitive
      impairment and have synergistic antidepressant effects. This study tested whether
      the addition of ketamine reduced cognitive impairment and enhanced efficacy over
      a course of ECT, in a randomised, placebo-controlled, double-blind study.
      METHODS: Fifty-one depressed patients treated with ultrabrief pulse-width right
      unilateral ECT were randomised to receive either ketamine (0.5mg/kg) or placebo
      (saline) in addition to thiopentone during anaesthesia for ECT.
      Neuropsychological outcomes (measured before ECT, after six treatments, and after
      the final ECT treatment) and mood outcomes (measured before ECT, and weekly after
      every three ECT treatments) were measured by a rater blinded to treatment
      condition. RESULTS: Neuropsychological outcomes did not differ between groups.
      The ECT-ketamine group had a slightly greater improvement in depressive symptoms
      over the first week of treatment and at one-week follow up, though there was no
      overall difference in efficacy at the end of the ECT course. No psychomimetic
      effects were detected. LIMITATIONS: The study was conducted in a clinical
      setting, so not all aspects of ECT treatment were fully controlled. Thiopentone
      doses differed slightly between groups, in order to accommodate the addition of
      ketamine to the anaesthetic. CONCLUSIONS: The addition of ketamine did not
      decrease cognitive impairment in patients having ultrabrief pulse-width right
      unilateral ECT, but was safe and slightly improved efficacy in the first week of
      treatment and at one-week follow up. CLINICAL TRIALS REGISTRATION:
      Clinicaltrials.gov ID: NCT00680433. Ketamine as an anaesthetic agent in
      electroconvulsive therapy (ECT). www.clinicaltrials.gov.

PMID- 22858220
TI  - Does executive functioning (EF) predict depression in clinic-referred adults? EF
      tests vs. rating scales.
AB  - BACKGROUND: Deficits in executive functioning (EF) are implicated in
      neurobiological and cognitive-processing theories of depression. EF deficits are
      also associated with Attention-deficit/hyperactivity disorder (ADHD) in adults,
      who are also at increased risk for depressive disorders. Given debate about the
      ecological validity of laboratory measures of EF, we investigated the
      relationship between depression diagnoses and symptoms and EF as measured by both
      rating scales and tests in a sample of adults referred for evaluation of adult
      ADHD. METHOD: Data from two groups of adults recruited from an ADHD specialty
      clinic were analyzed together: Adults diagnosed with ADHD (N=146) and a clinical
      control group of adults referred for adult ADHD assessment but not diagnosed with
      the disorder ADHD (N=97). EF was assessed using a rating scale of EF deficits in
      daily life and a battery of tests tapping various EF constructs. Depression was
      assessed using current and lifetime SCID diagnoses (major depression, dysthymia)
      and self-report symptom ratings. RESULTS: EF as assessed via rating scale
      predicted depression across measures even when controlling for current anxiety
      and impairment. Self-Management to Time and Self-Organization and Problem-Solving
      showed the most robust relationships. EF tests were weakly and inconsistently
      related to depression measures. LIMITATIONS: Prospective studies are needed to
      rigorously evaluate EF problems as true risk factors for depressive onset.
      CONCLUSIONS: EF problems in everyday life were important predictors of
      depression. Researchers and clinicians should consistently assess for the ADHD
      depression comorbidity. Clinicians should consider incorporating strategies to
      address EF deficits when treating people with depression.

PMID- 22858222
TI  - Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic
      nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE
      acyclic moiety.
AB  - Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine
      (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)
      HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The
      activity of the prodrugs was evaluated in vitro against different virus families.
      Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive,
      monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced
      antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)
      HPMPG emerged as the most potent and selective derivatives against these DNA
      viruses. None of the compounds were inhibitory against RNA viruses and
      retroviruses.

PMID- 22858223
TI  - Anti-HIV activity of semisynthetic derivatives of andrographolide and
      computational study of HIV-1 gp120 protein binding.
AB  - Andrographolide, a diterpene lactone of the Andrographis paniculata, displays
      anti-HIV activity in vitro. A series of andrographolide derivatives have been
      synthesized and evaluated for their anti-HIV activity in a cell-free virus
      infectivity assay using TZM-bl cells. As compared to andrographolide, 3
      nitrobenzylidene derivative 6 showed higher in vitro anti-HIV activity, whereas
      2',6'-dichloro-nicotinoyl ester derivative 9 showed higher Therapeutic Index. The
      andrographolide and its derivatives, 6 and 9, inhibited gp120-mediated cell
      fusion of HL2/3 cells (expressing gp120 on its surface) with TZM-bl cells
      (expressing CD4 and co-receptors CCR5 & CXCR4). Further, computational studies
      revealed that these molecules bind to the important residues of V3 loop of gp120.
      These results suggest that andrographolide derivatives may be promising
      candidates for prevention of HIV infection.

PMID- 22858224
TI  - Drugs for stroke: action of nitrone (Z)-N-(2-bromo-5-hydroxy-4
      methoxybenzylidene)-2-methylpropan-2-amine oxide on rat cortical neurons in
      culture subjected to oxygen-glucose-deprivation.
AB  - The action of (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2
      amine oxide (RP6) on rat cortical neurons in culture, under oxygen-glucose
      deprivation conditions, is reported. Cortical neurons in culture were treated
      during 1 h with OGD. After, they were placed under normal conditions during 24 h
      (reperfusion) in absence and presence of RP6. Different parameters were measured
      under each condition (control, 1 h OGD and 1 h OGD + reperfusion in absence and
      presence of RP6). RP6 protects neurons against ROS generation, lipid peroxidation
      levels, LDH release and mitochondrial membrane potential alteration, when
      administered during reperfusion after the OGD damage. Consequently, these results
      show that nitrone RP6 protects cells against ischemia injury produced during the
      reoxygenation, and could be a potential drug for the ictus therapy.

PMID- 22858225
TI  - The synthesis, spectroscopic, X-ray characterization and in vitro cytotoxic
      testing results of activity of five new trans-platinum(IV) complexes with
      functionalized pyridines.
AB  - Platinum(IV) complexes with general formulas [Pt(L(1-2))(2)Cl(4)], where L(1-2)
      are 3-acetylpyridine (1) and 4-acetylpyridine (2) respectively, and [Pt(HL(3
      5))(2)Cl(2)], where H(2)L(3-5) are 2,3-pyridinedicarboxylic acid (3), 2,4
      pyridinedicarboxylic acid (4) and 2,5-pyridinedicarboxylic acid (5) respectively,
      were prepared by the reaction of K(2)[PtCl(6)] with the corresponding ligand in
      1:2 M ratio in water. The complexes were characterized by elemental analysis and
      IR and NMR spectroscopy. The structures of complexes 2 and 5 were determined by X
      ray crystallography, which revealed the trans orientation of chloride anions
      around platinum(IV) in the case of both complexes. The antiproliferative activity
      was investigated in six tumor cell lines (human cervical carcinoma cells (HeLa),
      murine melanoma cells (B16), human breast carcinoma cells (MDA-MB-453), human
      colon carcinoma cells (LS-174), transformed human umbilical vein endothelial
      cells (EA.hy 926) and murine endothelial cells (MS1)) and in one non-tumor cell
      line-human fetal lung fibroblast cells (MRC-5). Cytotoxicity studies indicated
      that Pt(IV) complexes with acetyl-substituted pyridine ligands exhibit
      significantly higher in vitro antiproliferative activity than the complexes with
      carboxylato-substituted pyridines. Complexes 1 and 2 showed antiproliferative
      activity in all tested tumor cell lines, with the highest potential in human
      endothelial cells EA.hy 926, since they had IC(50) values of 13.8 +/- 5.8 MUM and
      23.4 +/- 3.3 MUM, respectively and were more active than cisplatin. Complexes 1
      and 2 exhibited lower toxicity against the non-tumor human lung fibroblast cell
      line (MRC-5) than against most of the tested tumor cell lines.

PMID- 22858226
TI  - F200Y polymorphism in the beta-tubulin gene in field isolates of Haemonchus
      contortus and risk factors of sheep flock management practices related to
      anthelmintic resistance.
AB  - Haemonchus contortus is the most prevalent and pathogenic nematode of sheep in
      tropical areas. The objectives of this study were to assess the frequency of the
      F200Y polymorphism on the beta-tubulin gene in third-stage larvae of H. contortus
      from 33 sheep flocks in Sao Paulo state, Brazil, and to associate this frequency
      to risk factors based on farm management practices. The resistance allele
      frequency varied from 9 to 74%, and the resistance genotype frequency varied from
      0 to 66.7%. Resistance genotype frequencies higher than 40% were associated with
      multiple risk factors - new sheep farming enterprises, the absence of farm
      records, the use of Dorper and Suffolk breeds, rotational grazing, the lack of
      wetlands on farms, pasture sharing with cattle or horses, frequent incorporation
      of animals into the flock, semi-intensive farming systems, whole-flock treatment,
      failure to use the FAMACHA method, lack of the dose-and-move practice,
      anthelmintic rotation after each application, visual estimation of animal weight
      for treatment, and lack of drug combination use. It can be concluded that
      genotyping the F200Y polymorphism can be used to monitor the resistance in sheep
      flocks and the knowledge of management strategies at the farm level is important
      to identify drug resistance related factors.

PMID- 22858227
TI  - Widespread occurrence of Trypanosoma vivax in bovines of tsetse- as well as non
      tsetse-infested regions of Ethiopia: a reason for concern?
AB  - A cross-sectional study was undertaken to assess the prevalence of bovine
      trypanosomosis in some tsetse-infested and tsetse-free areas of Ethiopia. From
      August 2010 till April 2011, a total of 1524 animals were parasitologically
      examined and compared by the haematocrit centrifugation technique (Woo test) and
      polymerase chain reaction (ITS-1 PCR). The ITS-1 PCR was more sensitive and more
      accurate in species identification than the Woo test. In ITS-1 PCR, an overall
      trypanosome prevalence of 31.0% was observed that is significantly (P<0.001)
      higher than in the Woo test (5.3%). Trypanosoma vivax was the predominant taxon
      (24.9%), followed by T. theileri (6.0%), T. congolense (2.9%) and Trypanozoon
      (1.6%). Mixed infections were quite common (14% of all infections). The overall
      prevalence of trypanosome infections in tsetse area (32.4%) was not different
      from non-tsetse area (30.5%) neither were the prevalences of T. vivax in both
      areas (respectively 22.6% and 25.7%). With these high prevalences, bovine
      trypanosomosis continues to hinder animal production and productivity in
      Ethiopia, both in tsetse-infested and non-infested parts of the country. Attempts
      to control African trypanosomosis should also pay attention to mechanically
      transmitted pathogenic trypanosomes and should adopt the most advanced molecular
      tests for species identification.

PMID- 22858228
TI  - Comparative evaluation of real time PCR assay with conventional parasitological
      techniques for diagnosis of Trypanosoma evansi in cattle and buffaloes.
AB  - For comparative evaluation, a real time PCR assay was standardized by using
      TaqMan primer and probe targeting the internal transcribed spacer 1 (ITS-1)
      region of rRNA for Trypanosoma evansi and sensitivity was evaluated by using DNA,
      extracted from diethyleamino ethane cellulose purified trypanosomes and
      trypanosomes infected whole blood of mice. The minimum detection limit for
      purified trypanosomal DNA was 0.01 ng (~ 0.33 genomic DNA of T. evansi) whereas
      for whole blood the minimum detection limit was 0.1 ng (~ 6.12 genomic DNA). T.
      evansi infected mice blood samples were collected at different interval post
      infection and were analysed by conventional parasitological methods (CPT) viz.
      wet blood smear, thin blood smear, thick blood smear, quantitative buffy coat and
      real time PCR and found that TaqMan assay was two fold sensitive than CPT in case
      of in vivo infectivity in mice and gave positive signal at 36 h post infection
      where as QBC and blood smear examination was able to detect at 60 h and 72 h post
      infection respectively. A total 109 (80 cattle and 29 buffaloes) blood samples
      were collected from in and around Ludhiana district and analysed by CPT and real
      time PCR. The overall prevalence of T. evansi by CPT in cattle and buffaloes was
      2.75 per cent. The prevalence rate was 2.5 per cent in cattle and 3.45 per cent
      in buffaloes. By real time PCR overall prevalence was 12.84 per cent in cattle
      and buffaloes, with a prevalence rate of 12.50 per cent in cattle and 13.79 per
      cent in buffaloes.

PMID- 22858229
TI  - Tubercle bacilli rely on a type VII army for pathogenicity.
AB  - Mycobacteria, such as the major human pathogen Mycobacterium tuberculosis, have a
      highly unusual and characteristic diderm cell envelope that protects them against
      harmful conditions. Protein secretion across this hydrophobic barrier requires
      specialized secretion systems. Recently, a type VII secretion (T7S) pathway has
      been identified that fulfills this function. Pathogenic mycobacteria have up to
      five different T7S systems, some of which play a crucial role in virulence. The
      interactions between secreted substrates and host molecules are only starting to
      become clear and will help in furthering our understanding of the persistence of
      these enigmatic pathogens. In this review, we discuss current knowledge on the
      role of T7S systems in mycobacterial virulence.

PMID- 22858230
TI  - UV-based advanced oxidation processes for the treatment of odour compounds:
      efficiency and by-product formation.
AB  - The occurrence of the taste and odour compounds geosmin and 2-methyl isoborneol
      (2-MIB) affects the organoleptic quality of raw waters from drinking water
      reservoirs worldwide. UV-based oxidation processes for the removal of these
      substances are an alternative to adsorption and biological processes, since they
      additionally provide disinfection of the raw water. We could show that the
      concentration of geosmin and 2-MIB could be reduced by VUV irradiation and the
      combination of UV irradiation with ozone and hydrogen peroxide in pure water and
      water from a drinking water reservoir. The figure of merit EE/O is an appropriate
      tool to compare the AOPs and showed that VUV and UV/O(3) yielded the lowest
      treatment costs for the odour compounds in pure and raw water, respectively.
      Additionally, VUV irradiation with addition of ozone, generated by the VUV lamp,
      was evaluated. The generation of ozone and the irradiation were performed in a
      single reactor system using the same low-pressure mercury lamp, thereby reducing
      the energy consumption of the treatment process. The formation of the undesired
      by-products nitrite and bromate was investigated. The combination of VUV
      irradiation with ozone produced by a VUV lamp avoided the formation of relevant
      concentrations of the by-products. The internal generation of ozone is capable to
      produce ozone concentrations sufficient to reduce EE/O below 1 kWh m(-3) and
      without the risk of the formation of nitrite or bromate above the maximum
      contaminant level.

PMID- 22858231
TI  - Effect of sow and piglet porcine circovirus type 2 (PCV2) vaccination on piglet
      mortality, viraemia, antibody titre and production parameters.
AB  - The present study describes the effects of sow and/or piglet porcine circovirus
      type 2 (PCV2) vaccination on viraemia, antibody response and production
      parameters (average daily weight gain [ADWG] and mortality) of piglets from a
      PCV2 subclinically infected farm. Four hundred seventy-six piglets born from
      vaccinated (V) or non-vaccinated (NV) sows were further subdivided in a total of
      four groups: NV sows-NV pigs (NV-NV, n=134), NV sows-V pigs (NV-V, n=135);V sows
      NV pigs (V-NV, n=104) and V sows-V pigs (V-V, n=103). A single vaccination of
      sows before mating was able to confer significantly higher antibody titres to
      their piglets at 4 weeks of age and a different PCV2 dynamics infection compared
      to piglets coming from NV sows. Piglet vaccination (independently of sow
      treatment) caused an earlier seroconversion and lower percentages of PCV2
      infected pigs compared to the NV ones throughout their life. The double PCV2
      vaccination strategy was able to reduce PCV2 infection but apparently caused some
      interference in piglet humoral response development. PCV2 vaccination was able to
      overcome this interference since the ADWG was improved in both groups of
      vaccinated piglets, independently of the sow treatment, being the highest ones
      obtained in the double vaccination group.

PMID- 22858232
TI  - Development and genetic influence of the rectal bacterial flora of newborn
      calves.
AB  - The aim of the study was to investigate a dynamic change in the rectal flora of
      calves as well as to study a genetic influence on the intestinal microflora of
      calves. The bacterial community of fecal samples from calves was examined by PCR
      single strand conformation polymorphism (PCR-SSCP) in two independent studies. In
      study one 14 newborn calves of the same farm were examined. Sampling was
      conducted directly after delivery (meconium) and after 6 h, 12 h, 24 h, 48 h, 3
      d, 7 d, 14 d and 42 d of life. In study two 6 twin calves and their coresident of
      the same age and farm were analysed in order to study for the first time whether
      genetic predisposition of the host may influence the fecal microflora. All calves
      were weaned directly after delivery and received pumped colostrum without direct
      contact to other farm animals. After delivery and during the first 12h of life
      the SSCP profiles were simple, but became more complex since the bacterial
      diversity increased with time in all calves. It became obvious that the intra
      individual band-pattern similarity decreased over time and inter-individual
      similarity was low. The analysis of fecal samples from twin calves revealed
      higher similarity in SSCP profiles for twins compared to their coresident
      indicating that the individual microflora might be genetically or epigenetically
      influenced. The insight that there are several conformities between intestinal
      microfloras of healthy calves and that there might be genetic influence on the
      fecal flora could help to prevent diarrhoeal diseases in the future.

PMID- 22858233
TI  - Predictors of improvement in patients with acute and chronic low back pain
      undergoing chiropractic treatment.
AB  - OBJECTIVES: The purpose of this study was to investigate outcomes and prognostic
      factors in patients with acute or chronic low back pain (LBP) undergoing
      chiropractic treatment. METHODS: This was a prognostic cohort study with medium
      term outcomes. Adult patients with LBP of any duration who had not received
      chiropractic or manual therapy in the prior 3 months were recruited from multiple
      chiropractic practices in Switzerland. Participating doctors of chiropractic were
      allowed to use their typical treatment methods (such as chiropractic
      manipulation, soft tissue mobilization, or other methods) because the purpose of
      the study was to evaluate outcomes from routine chiropractic practice. Patients
      completed a numerical pain rating scale and Oswestry disability questionnaire
      immediately before treatment and at 1 week, 1 month, and 3 months after the start
      of treatment, together with self-reported improvement using the Patient Global
      Impression of Change. RESULTS: Patients with acute (<4 weeks; n = 523) and
      chronic (>3 months; n = 293) LBP were included. Baseline mean pain and disability
      scores were significantly (P < .001) higher in patients with acute LBP. In both
      groups of patients, there were significant (P < .0001) improvements in mean
      scores of pain and disability at 1 week, 1 month, and 3 months, although these
      change scores were significantly greater in the acute group. Similarly, a greater
      proportion of patients in the acute group reported improvement at each follow-up.
      The most consistent predictor was self-reported improvement at 1 week, which was
      independently associated with improvement at 1 month (adjusted odds ratio [OR],
      2.4 [95% confidence interval, 1.3-4.5] and 5.0 [2.4-10.6]) and at 3 months (2.9
      [1.3-6.6] and 3.3 [1.3-8.7]) in patients with acute and chronic pain,
      respectively. The presence of radiculopathy at baseline was not a predictor of
      outcome. CONCLUSIONS: Patients with chronic and acute pain reporting that they
      were "much better" or "better" on the Patient Global Impression of Change scale
      at 1 week after the first chiropractic visit were 4 to 5 times more likely to be
      improved at both 1 and 3 months compared with patients who were not improved at 1
      week. Patients with acute pain reported more severe pain and disability initially
      but recovered faster. Patients with chronic and acute back pain both reported
      good outcomes, and most patients with radiculopathy also improved.

PMID- 22858234
TI  - Response of pain intensity to soft tissue mobilization and neurodynamic
      technique: a series of 18 patients with chronic carpal tunnel syndrome.
AB  - OBJECTIVE: The purpose of this prospective case series was to examine the
      combined effects of soft tissue mobilization and nerve slider neurodynamic
      technique on pain and pressure sensitivity in women with chronic carpal tunnel
      syndrome (CTS). METHODS: Eighteen women with a clinical and electromyographic
      diagnosis of CTS participated. Patients completed the numerical pain rating scale
      (NPRS) for current, worst, and lowest pain intensity and underwent pain pressure
      threshold (PPT) testing over the median, radial, and ulnar nerves; the C5-C6
      zygapophyseal joint; the carpal tunnel; and the tibialis anterior muscle. Pain
      was assessed at baseline and 1-week follow-up, whereas PPT were assessed at
      baseline and immediately after and 1-week after intervention. Each received soft
      tissue mobilization and nerve slider neurodynamic technique directed at different
      anatomical sites of potential entrapment of the median nerve. RESULTS: A decrease
      in the mean current intensity and worst level of hand pain (P<.01) was found 1
      week after the treatment session (mean changes, 2.2+/-1.1 points). A treatment
      effect for PPT levels over the C5-C6 zygapophyseal joint (P<.001) was found: PPT
      increased bilaterally 1 week after the intervention. No other significant changes
      in PPT levels were found (P>.195). CONCLUSIONS: The application of soft tissue
      mobilization and neurodynamic technique decreased the intensity of pain but did
      not change pressure pain sensitivity in this group of women with chronic CTS.

PMID- 22858236
TI  - Interest in cosmetic vulvar surgery and perception of vulvar appearance.
AB  - OBJECTIVE: The objective of the study was to determine whether reproductive-age
      women are more likely to perceive their vulva as abnormal compared with older
      aged women. STUDY DESIGN: Women aged 18-44 years (group 1) and 45-72 years (group
      2) completed a survey on demographics, grooming patterns, vulvar perceptions, and
      source of information about the vulva. RESULTS: There was no difference between
      group 1 and group 2 in how often women looked at their vulva or their perception
      of having a normal vulva (91% vs 93%, P = .76). Both groups were satisfied with
      the appearance of their vulva (81% vs 82%, P = .71). A higher percentage in group
      2 would consider cosmetic surgery if cost were not an issue versus group 1 (15%
      vs 8%, P = .05). CONCLUSION: A woman's age does not have an impact on her
      perception of a normal vulva. The majority of women perceived their vulva to be
      normal and were satisfied with its appearance. However, older women are more
      interested in cosmetic vulvar surgery.

PMID- 22858235
TI  - Impact of paroxetine on sleep problems in 426 cancer patients receiving
      chemotherapy: a trial from the University of Rochester Cancer Center Community
      Clinical Oncology Program.
AB  - BACKGROUND: Sleep problems are a frequent distressing symptom in cancer patients,
      yet little is known about their treatment. Sleep problems and depression
      frequently co-occur, leading healthcare professionals to treat depression with
      the expectation that sleep problems will also improve. The purpose of this study
      was to compare the effect of paroxetine to placebo on sleep problems via a
      secondary data analysis of a RCT designed to compare the effects of paroxetine to
      placebo on fatigue in cancer patients undergoing chemotherapy. A previously
      published report found a significant effect of paroxetine on depression in this
      cohort. METHODS: A total of 426 patients were randomized following Cycle 2 of
      chemotherapy to receive either 20mg of paroxetine or placebo. Sleep problems were
      assessed using questions from the Hamilton Depression Inventory three times
      during chemotherapy. RESULTS: A total of 217 patients received paroxetine and 209
      received placebo. Significantly fewer patients taking paroxetine reported sleep
      problems compared to patients on placebo (Paroxetine 79% versus Placebo 88%;
      p<0.05). These differences remained significant even after controlling for
      baseline sleep problems and depression (p<0.05). CONCLUSION: Paroxetine had a
      significant benefit on sleep problems in both depressed and non-depressed cancer
      patients. However, rates of sleep problems remained high even among those
      effectively treated for depression with paroxetine. There is a need to develop
      and deliver sleep-specific interventions to effectively treat sleep-related side
      effects of cancer treatments. These findings suggest that sleep problems and
      depression are prevalent and co-morbid. Cancer progression, its response to
      treatment, and overall patient survival are intricately linked to host factors,
      such as inflammatory response and circadian rhythms, including sleep/wake cycles.
      Sleep problems and depression are modifiable host factors that can influence
      inflammation and impact cancer progression and quality of life. Future research
      should focus on discovering the pathogenesis of sleep dysregulation and
      depression in cancer so that better treatment approaches can be developed to
      ameliorate these symptoms.

PMID- 22858237
TI  - The impact of organizational factors on the urinary incontinence care quality in
      long-term care hospitals: a longitudinal correlational study.
AB  - BACKGROUND: With the rapid increase in the number of long-term care hospitals in
      Korea, care quality has become an important issue. Urinary incontinence is an
      important condition affecting many residents' quality of life. Thus, it is
      important that urinary incontinence be amenable to improving conditions with
      appropriate interventions, since a change in urinary incontinence status can
      reflect care quality in long-term care facilities if patient level factors are
      adjusted. OBJECTIVES: We aim to examine the impact of organizational factors on
      urinary incontinence care quality defined as the improvement of urinary
      incontinence status or maintenance of continent status post-admission to Korean
      long-term care hospitals. DESIGN AND DATA: This is a longitudinal correlation
      study. Data came from two sources: monthly patient assessment reports using the
      Patient Assessment Instrument and the hospital information system from the Health
      Insurance Review and Assessment Services. The final analysis includes 5271
      elderly adults without indwelling urinary catheter or urostomy who were admitted
      to 534 Korean long-term care hospitals in April 2008. METHODS: Multi-level
      logistic analysis was used to explore the organizational factors that influence
      urinary incontinence care quality controlling for patient level factors. RESULTS:
      With respect to the organizational factors, the findings showed that location and
      RN/total nursing staff ratio variables were statistically significant,
      controlling for risk factors at the patient level. The odds of urinary
      incontinence improvement from admission in urban long-term care hospitals were
      1.28 times higher than rural long-term care hospitals. In addition, when a long
      term care hospital increased one standard deviation (0.19) in the RN ratio, the
      odds of urinary incontinence status improvement or maintenance of continence
      status from admission increased about 1.8 times. CONCLUSIONS: The most
      significant finding was that a higher RN to patient ratio and urban location were
      associated with better resident outcomes of urinary incontinence among
      organizational factors. For a better understanding of how these significant
      organizational factors influence positive care outcomes and provide more
      practical implications, studies should examine concrete care process measures as
      well as structure and outcome measures based on systematic conceptual models.

PMID- 22858238
TI  - Employment goals, expectations, and migration intentions of nursing graduates in
      a Canadian border city: a mixed methods study.
AB  - BACKGROUND: Internationally, nurse migration in border cities has received little
      attention. Nurses who graduate from nursing programs in Canadian border
      communities have the option of working in Canada or the United States. They are
      able to cross the international border each day as commuter migrants returning to
      their home country after work. Despite recent investment by Canada to increase
      the number of nursing students, the migration intentions of graduating nurses and
      the factors influencing their decision making has not been explored. OBJECTIVES:
      The objective of this study is to explore the migration intentions of a
      graduating class of baccalaureate nursing students in a Canadian border community
      and the factors influencing their decision making. METHODS: An explanatory
      sequential mixed methods design was used. In the first quantitative phase, data
      was collected by a web-based self-report survey. In the qualitative phase, semi
      structured interviews were conducted. Data collection took place between February
      and July 2011. RESULTS: The response rate to the survey was 40.9% (n=115). Eighty
      six percent of graduates preferred to work in Canada although two thirds
      identified that they were considering migrating for work outside of Canada.
      Knowing a nurse who worked in the US (Michigan) influenced intention to migrate
      and living in a border community was a strong predictor of migration. Migrants
      had significantly higher expectations that their economic, professional
      development, healthy work environment, adventure and autonomy values would be met
      in another country than Canada. Evidence from the interviews revealed that
      clinical instructors and clinical experiences played a significant role in
      framing students' perceptions of the work environment, influencing their choice
      of specialty, and where they secured their first job. CONCLUSION: The value
      expectancy framework offered a novel approach to identifying job factors driving
      migration intentions. The study offered a snapshot of the graduates' perception
      of the work environment before entering the workforce. The graduates doubted that
      their future work environment would meet many of their job expectations, a
      troubling finding requiring further investigation. Expectations influenced their
      migration intentions and may be relevant to their integration and retention in
      the workforce.

PMID- 22858239
TI  - Dynamic vascular changes following intravenous antibiotics in patients with
      cystic fibrosis.
AB  - BACKGROUND: Adults with cystic fibrosis (CF) have altered large artery
      haemodynamics which is associated with a persisting systemic inflammatory state.
      We hypothesized that a short-term intervention favorably influencing the
      inflammatory status may modify their haemodynamic state. METHODS: Adult patients
      with CF were studied immediately preceding and following 2 weeks of intravenous
      antibiotics. Large artery haemodynamics, principally heart rate-adjusted
      augmentation index (AIx) were obtained. Blood pressure (BP), spirometry and CRP
      were also measured. RESULTS: Complete data was available for 15 patients; mean
      (SD) age 28 (6)years. CRP was reduced while FEV1% predicted improved. Following
      treatment AIx was lower: 10.9 (10.9)% to 8.1 (10.9)% (p<0.05) while BP was
      similar and a trend toward lower heart rate (p=0.06). Change in AIx was related
      to baseline FEV1% predicted (r=0.77) and BMI (r=0.71) (both P<0.01). CONCLUSION:
      The abnormal central haemodynamics evident in adults with CF is modulated with a
      short intervention of intravenous antibiotics.

PMID- 22858240
TI  - Postoperative changes in mandibular prognathism surgically treated by intraoral
      vertical ramus osteotomy.
AB  - This study investigated short- and long-term postoperative skeletal changes
      following intraoral vertical ramus osteotomy (IVRO) for mandibular prognathism,
      as determined from lateral cephalograms. The subjects were 20 patients with
      mandibular prognathism who had undergone surgical orthodontic treatment combined
      with IVRO. Lateral cephalograms were taken at six time points: 1 month before
      surgery, and 1 day, 3 months, 6 months, 1 year, and approximately 2 years after
      surgery. Intermaxillary fixation (IMF) with four monocortical screws was
      maintained for 1 week in all patients. Mean posterior movement of the menton (Me)
      was 5.9 mm at surgery. 3 months after surgery, the FMA and FH-CorMe angles had
      increased 6.3 and 6.2 degrees, respectively, indicating clockwise rotation of the
      distal segment of the mandible. This rotation was observed in all 20 patients,
      suggesting that postoperative rotation of the mandible in the postoperative short
      term is likely to occur after IVRO and could be considered an adaptation of the
      mastication system newly established by surgery. In the long term after IVRO, Me
      had moved anteriorly by only 0.9 mm and the relapse ratio was 15.3%. These
      findings suggest the excellent long-term stability of surgical orthodontic
      treatment combined with IVRO in patients with mandibular prognathism.

PMID- 22858241
TI  - Notes on the use of urine-CCA dipsticks for detection of intestinal
      schistosomiasis in preschool children.
AB  - Urine-dipstick diagnostic tests that detect schistosome circulating cathodic
      antigen (CCA) have the potential to provide more sensitive and rapid testing for
      intestinal schistosomiasis in field-based surveys; this is especially so when
      examining preschool children, from whom it may be difficult to obtain consecutive
      stool samples. To assess the performance of urine dipsticks, 569 preschool
      children from four villages along the shore of Lake Albert, Uganda, were screened
      for Schistosoma mansoni by Kato-Katz (K-K) examination of a single stool sample
      and CCA urine dipsticks. The prevalence of infection was 32.2% by K-K and 40.0%
      by CCA tests. Sensitivity and specificity were influenced by whether 'trace'
      results from the CCA test were characterised as positive or negative for
      infection with S. mansoni; ambiguities around this issue need to be resolved.
      Nevertheless, the CCA test showed particular promise for routine epidemiological
      screening in this setting.

PMID- 22858242
TI  - Zebrafish: an emerging model of vascular development and remodelling.
AB  - The zebrafish has attracted interest from both the scientific and general press
      owing to its transition from a model of developmental biology to a tool for
      biomedical and preclinical studies. In this brief review, we summarise the
      advantages of a unique model organism and outline some of its recent
      contributions to the understanding of vascular development and remodelling.

PMID- 22858244
TI  - A multi-segment foot model based on anatomically registered technical coordinate
      systems: method repeatability and sensitivity in pediatric planovalgus feet.
AB  - Several multisegment foot models have been proposed and some have been used to
      study foot pathologies. These models have been tested and validated on typically
      developed populations; however application of such models to feet with
      significant deformities presents an additional set of challenges. For the first
      time, in this study, a multisegment foot model is tested for repeatability in a
      population of children with symptomatic abnormal feet. The results from this
      population are compared to the same metrics collected from an age matched (8-14
      years) typically developing population. The modified Shriners Hospitals for
      Children, Greenville (mSHCG) foot model was applied to ten typically developing
      children and eleven children with planovalgus feet by two clinicians. Five
      subjects in each group were retested by both clinicians after 4-6 weeks. Both
      intra-clinician and inter-clinician repeatability were evaluated using static and
      dynamic measures. A plaster mold method was used to quantify variability arising
      from marker placement error. Dynamic variability was measured by examining trial
      differences from the same subjects when multiple clinicians carried out the data
      collection multiple times. For hindfoot and forefoot angles, static and dynamic
      variability in both groups was found to be less than 4 degrees  and 6 degrees 
      respectively. The mSHCG model strategy of minimal reliance on anatomical markers
      for dynamic measures and inherent flexibility enabled by separate anatomical and
      technical coordinate systems resulted in a model equally repeatable in typically
      developing and planovalgus populations.

PMID- 22858243
TI  - Systems biology: personalized medicine for the future?
AB  - Systems biology is actively transforming the field of modern health care from
      symptom-based disease diagnosis and treatment to precision medicine in which
      patients are treated based on their individual characteristics. Development of
      high-throughput technologies such as high-throughout sequencing and mass
      spectrometry has enabled scientists and clinicians to examine genomes,
      transcriptomes, proteomes, metabolomes, and other omics information in
      unprecedented detail. The combined 'omics' information leads to a global
      profiling of health and disease, and provides new approaches for personalized
      health monitoring and preventative medicine. In this article, we review the
      efforts of systems biology in personalized medicine in the past 2 years, and
      discuss in detail achievements and concerns, as well as highlights and hurdles
      for future personalized health care.

PMID- 22858245
TI  - Effects of obesity on dynamic plantar pressure distribution in Chinese
      prepubescent children during walking.
AB  - The purpose of this study was to examine the effects of obesity on dynamic
      plantar pressure distribution during walking for prepubescent children. A
      footscan((r)) plantar pressure plate system was used to collect the gait data.
      Fifty obese prepubescent children and fifty non-obese prepubescent children
      walked across the plate at preferred speed while barefoot. SPSS11.5 was used for
      analysis and significance is defined as p<0.05. Obese subjects had longer
      midstance duration (p=0.004) and shorter propulsion duration (p=0.047) compared
      to non-obese subjects. The peak pressures under the metatarsal heads II-V,
      midfoot and heel lateral (p=0.004, p=0.03, p=0.004) were significantly higher for
      obese subjects. The time to peak pressures under the toes II-V, the metatarsal
      heads IV, V and midfoot (p=0.008, p=0.009, p=0.01, p=0.006), and pressure rate
      under the heel medial and lateral heel (p=0.03, p=0.009) were also significantly
      higher. In addition, the arch index for the left foot (p=0.01), the left and
      right foot axis angle (p=0.027, p=0.03) were significant larger among obese
      subjects. We also found that obese subjects had significantly higher relative
      regional impulses of contact with the plate at the midfoot of left foot (p=0.01)
      and the forefoot of right foot (p=0.047). There were also differences in foot
      balance during the midstance and propulsion phase (p=0.0004, p=0.03) and in
      pronation extent during midstance and propulsion phases between left and right
      foot in the obese group (p=0.03, p=0.01). In conclusion, the obese children have
      weaker walking stability with flatter foot pattern, the larger foot axis angle
      and dynamic plantar pressure distribution changes compared to non-obese children.

PMID- 22858246
TI  - Early left ventricular abnormalities in children with heterozygous familial
      hypercholesterolemia.
AB  - BACKGROUND: Few data are available on cardiac morphology and function in children
      with heterozygous familial hypercholesterolemia (FH). Such patients represent a
      unique clinical model to assess the effect of pure hypercholesterolemia on
      cardiac morphology and function, excluding the effect of comorbidities. Speckle
      tracking echocardiography, a relatively new echocardiographic modality, allows
      the assessment of myocardial deformation properties. The aim of this study was to
      define in children with FH the preclinical effects of isolated
      hypercholesterolemia on the cardiovascular system by examining left ventricular
      (LV) function using speckle-tracking echocardiography. METHODS: Ninety children
      (45 with FH and 45 controls; mean age, 11 +/- 3 years) were prospectively
      studied. RESULTS: Children with FH showed thicker LV walls and significantly
      higher LV mass indexed for height(2.7) (P = .0008) and for body surface area (P <
      .0001). LV ejection fractions were similar in both groups. Assessment of
      diastolic function demonstrated longer deceleration times (P < .0001), reduced
      early diastolic mitral annular velocities (P < .0001), and higher transmitral
      early/early diastolic mitral annular velocity ratios (P = .0003) in children with
      FH. Longitudinal and circumferential myocardial deformation of the left ventricle
      were significantly reduced (P < .0001) whereas radial deformation was increased
      in children with FH (P = .04) compared with controls. CONCLUSIONS: This study
      demonstrates that hypercholesterolemia is associated with significant LV
      morphologic and functional alterations during childhood. The findings also
      suggest that reductions in longitudinal and circumferential deformation are
      compensated for by increasing radial strain in children with FH with normal LV
      ejection fractions. This study raises the questions of the clinical importance of
      these findings and the opportunity for cholesterol-lowering therapy. The
      potential benefits and risks of such treatment at a young age need to be
      addressed in larger long-term studies.

PMID- 22858247
TI  - An exaggerated blood pressure response to treadmill exercise does not increase
      the likelihood that exercise echocardiograms are abnormal in men or women.
AB  - BACKGROUND: Some experts have suggested that patients with exaggerated blood
      pressure responses during exercise echocardiography are more likely to have
      abnormal exercise echocardiographic findings and less likely to have
      angiographically significant coronary artery disease than patients with normal
      blood pressure responses. The aim of this study was to evaluate the impact of
      exercise blood pressure on exercise echocardiographic findings and subsequent
      angiographic results in men and women. METHODS: In this retrospective study,
      clinical, exercise, and echocardiographic characteristics of patients who
      underwent treadmill exercise echocardiography over a 2-year period were examined,
      and the angiographic findings of the subgroup of patients who subsequently
      underwent coronary angiography within 30 days were analyzed. RESULTS: Among the
      7,015 patients (mean age, 61 +/- 13 years), 3,992 were men (57%). The likelihood
      of patients' having abnormal exercise echocardiographic results was similar at
      all levels of exercise blood pressure, except in men who had low peak systolic
      blood pressures (<120 mm Hg); they had the highest rate of abnormal exercise
      echocardiographic findings. Of the 3,225 patients without histories of
      hypertension or coronary artery disease, 3,098 had peak systolic blood pressures
      of 120 to 219 mm Hg (a "normal" blood pressure response), and 59 had peak
      systolic blood pressures >= 220 mm Hg (an exaggerated blood pressure response).
      These patients with exaggerated blood pressure responses were just as likely to
      have normal exercise echocardiographic results as those who had normal blood
      pressure responses (85% vs 83%, P > .99). A subgroup of 508 patients underwent
      coronary angiography. The rate of false-positive findings was similar for
      patients who had exaggerated blood pressure responses and those who had normal
      blood pressure responses. The false-positive rate tended to be lower in patients
      who had low blood pressure responses. CONCLUSIONS: Patients who have exaggerated
      blood pressure responses to exercise are not more likely to have abnormal
      exercise echocardiographic findings than those with normal blood pressure
      responses. The majority of patients who have echocardiographic abnormalities and
      subsequently undergo coronary angiography have substantial (>=50% stenosis)
      coronary artery disease.

PMID- 22858248
TI  - Photodynamic therapy of malignant brain tumours: a complementary approach to
      conventional therapies.
AB  - The poor outcome of primary malignant brain tumours is predominantly due to local
      invasion and local recurrence and their prognosis is highly dependent on the
      degree of resection. They have no border and, at best, a marginal zone that
      remains invisible to the surgeon. Photodynamic therapy (PDT) appears to be an
      interesting modality to fill the need for a targeted treatment that may reduce
      recurrence and extend survival with minimal side effects. In this review, we
      summarize the different technologies of brain tumour PDT employed such as
      interstitial PDT, and PDT-associated surgical resection, describing new light
      delivery devices. The role of dosimetry - one of the key factors behind
      successful brain tumour PDT - is discussed. This can be achieved by integrating
      results from in vivo studies. In this context, the development of new therapeutic
      photosensitizer delivery systems is also an area of significant research
      interest. Multifunctionality can be engineered into a single nanoplatform to
      provide tumour-specific detection, treatment, and follow-up. Such multitasking
      systems appear to be complementary to conventional technologies.

PMID- 22858249
TI  - Does interleukin-6 link explain the link between tumour necrosis, local and
      systemic inflammatory responses and outcome in patients with colorectal cancer?
AB  - Cancer-associated inflammation has been identified as a key determinant of
      disease progression and survival in colorectal cancer. In particular, it has been
      consistently reported that both the local and systemic inflammatory responses
      play an important role in determining outcome in colorectal cancer. Given the
      importance of cancer-associated inflammation, up-regulation or attenuation of
      these respective inflammatory responses may be important for progression and
      survival in colorectal cancer. Recent work has focused on the inter-relationships
      between the tumour and these key inflammatory processes. In particular, tumour
      necrosis has been reported to be associated with decreased local inflammatory
      infiltrate and with elevated markers of systemic inflammation in colorectal
      cancer and has been proposed as a potential link between the systemic and local
      inflammatory responses. Thus there is increasing interest in the potential
      biochemical mediators of this link. In this review we examine the evidence for IL
      6 in the natural history of colorectal cancer and its relationship with tumour
      necrosis and the local and systemic inflammatory responses. There is now good
      evidence that tumour concentrations of IL-6 have been directly associated with
      increased necrosis, proliferation, differentiation and vascular invasion, while
      circulating concentrations of IL-6 are directly associated with T-stage, CRP
      concentrations and poorer survival. Also, interleukin-6 and down-stream pathways,
      such as the JAK/STAT pathway, have emerged as important factors in the modulation
      of cancer-associated inflammation. Therefore, IL-6 has emerged as a key mediator
      of the relationship between tumour necrosis, local and systemic inflammatory
      responses and outcome in patients with colorectal cancer.

PMID- 22858250
TI  - Factors related to different reasons for antipsychotic drug discontinuation in
      the treatment of schizophrenia: a naturalistic 18-month follow-up study.
AB  - In recent years, measurement of the effectiveness of antipsychotic therapy in
      schizophrenia has received increasing attention from clinicians and researchers.
      Several studies have used time to antipsychotic discontinuation for any reason as
      a global index of antipsychotic effectiveness because it reflects both the
      physician's and patient's judgment of drug efficacy and tolerability. In this
      study, we extend this approach by analyzing the rate of discontinuation for
      different reasons of antipsychotics administered to patients with schizophrenia
      in a naturalistic setting of care, and explore the determinants of such
      discontinuation. Ninety-nine patients with schizophrenia who received a first or
      second generation antipsychotic were followed for 18 months in the Italian
      outpatient community psychiatric system. We found discontinuation rates for
      different reasons to be variable and to be influenced by several factors not
      involving the type of pharmacologic therapy. Some of these factors, such as the
      frequency of visits to the care unit, underline the need to take into account the
      role of the care delivery system as potentially influencing the effectiveness of
      antipsychotics in the "real world".

PMID- 22858251
TI  - Changes in facets of mindfulness and posttraumatic stress disorder treatment
      outcome.
AB  - Though there has been a recent surge of interest in the relations between facets
      of mindfulness and Posttraumatic Stress Disorder (PTSD), there has been a dearth
      of empirical studies investigating the impact of changes in facets of mindfulness
      on PTSD treatment outcomes. The present study tested the prospective associations
      between pre- to post-treatment changes in facets of mindfulness and PTSD and
      depression severity at treatment discharge, among 48 military Veterans in
      residential PTSD treatment adhering to a cognitive-behavioral framework.
      Together, changes in facets of mindfulness significantly explained post-treatment
      PTSD and depression severity (19-24% of variance). Changes in acting with
      awareness explained unique variance in post-treatment PTSD severity and changes
      in nonjudgmental acceptance explained unique variance in post-treatment
      depression severity. These results remained significant after adjusting for
      shared variance with length of treatment stay.

PMID- 22858252
TI  - Homeostatic mechanisms by alternative forms of tRNA synthetases.
AB  - Although aminoacyl tRNA synthetases (aaRSs) act in translation, numerous examples
      demonstrate ex-translational functions in fundamental networks of higher
      organisms. These functions involve modified versions of aaRSs and natural
      fragments. The interplay of aaRS-derived entities appears to be at the heart of
      homeostatic mechanisms controlling angiogenesis, inflammation, metabolism, and
      tumorigenesis.

PMID- 22858253
TI  - Long-term duration of function of ovarian tissue transplants: case reports - how
      many swallows make a summer?

PMID- 22858254
TI  - Ovarian cryopreservation: experimental or established and a cure for the
      menopause?
AB  - Long-term (>7 years) duration of function of ovarian cortical tissue grafts in
      three patients who have had several successful pregnancies is encouraging and
      requires us to carefully examine the risk benefit analysis of this technique for
      our future patients. However, the success rate for ovarian cryopreservation is
      unclear as the denominator (the number of women in whom frozen-thawed ovarian
      tissue has been re-implanted) is unknown. There still remain many unknowns and
      much more research is required before ovarian transplantation can be considered
      standard practice. The ability of ovarian cryopreservation to preserve fertility
      for some young survivors of cancer is proven, but the indications for which
      patients should be offered this exciting new technology are not yet established.

PMID- 22858255
TI  - Function of ovarian tissue after long-term storage.
AB  - Ovarian tissue cryopreservation is one of the options available to preserve
      fertility in cancer patients and to allow them to conceive when they have
      overcome their primary disease. The publication of a report by Anderson and
      colleagues documenting live births in three women arising from ovarian cortical
      strips that had been transplanted more than 7 years previously represents an
      apparent further advance in this field.

PMID- 22858256
TI  - Chemical and toxicological evaluation of an emerging pollutant (enrofloxacin) by
      catalytic wet air oxidation and ozonation in aqueous solution.
AB  - This study evaluates the degradation efficiency of enrofloxacin (ENR) by
      catalytic wet air oxidation (CWAO) and ozonation. Results obtained by CWAO
      experiments show that 99.5% degradation, 37.0% chemical oxidation demand (COD)
      removal and 51.0% total organic carbon (TOC) conversion were obtained when 100
      mol% FeCl(3) and 25 mol% NaNO(2) at 150  degrees C under 0.5 MPa oxygen pressure
      after 120 min are used. The degradation products are identified by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass
      spectrometry (GC-MS) and ion chromatography (IC). The oxidation end products, F(
      ), NO(3)(-) and NH(4)(+) were determined by IC. The BOD(5)/COD ratio as a measure
      of the biodegradability of the parent compound increased from 0.01 to 0.12 after
      120 min of reaction time, indicating an improved biodegradability of the parent
      compound. The inhibition of bioluminescence of the marine bacteria V. fischeri
      decreased from 43% to 12% demonstrating a loss in toxicity of ENR during CWAO.
      Ozonation of 0.2 mM ENR was carried out with an ozone concentration of 7.3 g m(
      3) at pH 7. ENR decomposition with a degradation rate of 87% was obtained
      corresponding to the reaction time. Moderate changes in COD (18%) and TOC (17%)
      removal has been observed. The bioluminescence inhibition increased from 8% to
      50%, due to the generation of toxic degradation products during ozonation. In
      comparison to the widely use of well developed method of ozonation CWAO exhibits
      better performance in terms of COD, TOC removals and generates less toxic
      products.

PMID- 22858257
TI  - The reaction of selenium (IV) with ascorbic acid: its relevance in aqueous and
      soil systems.
AB  - Abiotic processes able to reduce oxidized Se species may have a strong influence
      on the environmental behavior of selenium since Se toxicity, bioavailability and
      mobility follow the order Se(-II)<Se(0)<Se(IV)<Se(VI). Ascorbic acid, which is
      exudated from plant roots, aquatic macrophytes and phytoplankton and also derives
      from decomposition of organic matter (e.g. litter, dead roots, algal cells), is
      present either in soil solution or in the water phase and may interact with Se
      affecting its speciation and environmental behavior. The rates of the reduction
      of Se(IV) by ascorbic acid (C(6)H(8)O(6)=H(2)A) were measured in NaCl and
      NaClO(4) solutions with 1 MUM Se(IV) and 100-1000 MUM H(2)A as a function of pH,
      temperature and ionic strength and in the presence of possible interfering
      metals. The rates of the reaction decreased abruptly with increasing of pH in the
      range 2-5.5, while slowly at lower pH. The rates showed a small influence of
      temperature in the range 10-40 degrees C and were independent of ionic strength
      from 0.01 M to 1M. The values of the second-order rate constant (k) calculated
      from the values of k(1)/[H(2)A](T) can be determined from the equation: log k = 
      0.92 * pH - 3368.4/T + 0.24 * I(0.5) + 16.94 for the pH range 2-5.5 (sigma=+/
      0.23), from 10 to 40  degrees C and from 0.01 to 1M ionic strength. The effect of
      pH and ionic strength on the reaction suggests that the second-order rate
      expression over the entire pH range investigated can be determined from
      (H(2)A=C(6)H(8)O(6); HA=C(6)H(7)O(6)(-); H(2)B=H(2)SeO(3); HB=HSeO(3)(-))
      [formula, see text] where K(HA), K(A), K(HB), K(B) are the dissociation constants
      of selenous acid and ascorbic acid, k(H2A-H2B)=5577+/-78 and k(H2A-HB)=812+/-102
      M(-1)h(-1). The presence of Cu(II), which is a strong catalyzer for the oxidation
      of H(2)A, decreases the rates of Se(IV) reduction by H(2)A in oxygenated waters.
      Mn(IV) causes an oxidation of Se(IV) to Se(VI) at high Mn(IV)/H(2)A molar ratios
      (>0.3), while does not affect significantly the reduction of Se(IV) by H(2)A at
      low ratios (<0.1). Fe(III) also catalyzes the oxidation of H(2)A but in this case
      the possible diminution of the reduction rates of Se(IV) by H(2)A are masked by
      additional processes of adsorption on and coprecipitation by ferric
      oxyhydroxides, which lower the concentrations of Se(IV).

PMID- 22858258
TI  - Effect of endophyte-infection on growth parameters and Cd-induced phytotoxicity
      of Cd-hyperaccumulator Solanum nigrum L.
AB  - The aim of this work was to evaluate effects of endophytic bacterium inoculation
      on plant growth and assess the possible mechanism of endophyte in heavy metal
      phytoremediation. Seeds of Solanum nigrum L. were inoculated with endophyte
      Serratia nematodiphila LRE07 and were subjected to Cd in the growing medium. Cd
      produced a significant inhibition on plant growth and a reduction in the content
      of photosynthetic pigments. The inoculation of endophytic bacterium alleviated
      the Cd-induced changes, resulting in more biomass production and higher
      photosynthetic pigments content of leaves compared with non-symbiotic ones. The
      beneficial effect was more obvious at relatively low Cd concentration (10 MUM).
      Based on the alteration of nutrient uptake and activated oxygen metabolism in
      infected plants, the possible mechanisms of endophytic bacterium in Cd
      phytotoxicity reduction can be concluded as uptake enhancement of essential
      mineral nutrition and improvement in the antioxidative enzymes activities in
      infected plant.

PMID- 22858259
TI  - A cross-cultural comparison of the phenotype of depression as measured by the
      Cornell Scale and the MADRS in two elderly outpatient populations.
AB  - BACKGROUND: Different cutoff points for a depressive disorder on depression
      scales exist in different countries. The reasons could be that the presence or
      the intensity of the various symptoms on the scales differ. We wanted to explore
      differences in scores on depression scales among patients in Brazil and Norway.
      METHODS: The Cornell Scale for Depression in Dementia (CSDD) and the Montgomery
      Aasberg Depression Rating Scale (MADRS) were completed independently among 211
      elderly outpatients in Brazil and Norway. A psychiatrist, blind to the results,
      diagnosed depression using the ICD-10 and DSM-IV criteria. RESULTS: According to
      the ICD-10 criteria, 29 (33.7%) Brazilian and 51 (40.8%) Norwegian patients had
      depression (p=0.3). Mean CSDD score was 14.4 (SD 8.9) in Brazil and 6.8 (SD 4.9)
      in Norway (p<0.001). Mean MADRS score was 13.2 (SD 12.1) in Brazil and 8.4 (SD
      6.8) in Norway (p=0.02). We analyzed the scores for the depressed and the non
      depressed patients separately. In both groups the Brazilian patients had
      significantly higher scores on both scales compared to the Norwegian patients. In
      an adjusted linear regression analysis the variable "country" was associated with
      the CSDD score (beta=-0.29, p=0.01). LIMITATIONS: The protocols in the two
      countries were not exactly the same. Only one psychiatrist evaluated the
      patients. CONCLUSIONS: The scores on the MADRS and the CSDD were higher in
      patients in Brazil than in Norway. In an adjusted linear regression analysis,
      "country" was the only variable associated with the higher CSDD score.

PMID- 22858260
TI  - Prior sleep problems predict internalising problems later in life.
AB  - BACKGROUND: One possible risk marker of later internalising symptoms is poor
      sleep, which is a problem for up to 40% of children. The present study
      investigated whether prior sleep problems could predict internalising symptoms
      over a period of 18 years of follow-up. METHODS: The study sample included 1503
      French young adults from the TEMPO cohort (mean age=28.8+/-3.6 years) whose
      parents participate in the GAZEL cohort study. All TEMPO participants previously
      took part in a study of children's mental health and behaviour in 1991 (mean
      age=10.3+/-3.6 years) and 1999 (mean age=18.8+/-3.6 years). Sleep problems and
      internalising symptoms (depression, anxiety, somatic complaints) were assessed
      three times (1991, 1999, 2009) using the Achenbach System of Empirically Based
      Assessment (ASEBA) questionnaire. The association between sleep problems in 1991
      and trajectories of internalising problems from 1991 to 2009 was tested in a
      multinomial logistic regression framework, controlling for sex, age, baseline
      temperament, behavioural problems and stressful life events, as well as family
      income, and parental history of depression. RESULTS: We identified four
      trajectories of internalising symptoms: high-persistent (2.5%), high-decreasing
      (11.4%), low-increasing (11.6%), and low-persistent (74.5%). After controlling
      for covariates, compared to participants who did not have sleep problems in 1991,
      those who did were 4.51 times (95% CI=1.54-13.19, P=.006) more likely to have
      high-persistent internalising symptoms and 3.69 times (95% CI=2.00-6.82, P<.001)
      more likely to have high-decreasing internalising symptoms over the 18-year
      follow-up. LIMITATIONS: Sleep problems and internalising symptoms were based on
      self-report questions, results should be interpreted with due caution.
      CONCLUSIONS: Sleep problems early in life are associated with an increased
      likelihood of internalising symptoms that persist from childhood to adulthood.

PMID- 22858261
TI  - Cardiovascular diseases do not influence the mental health outcome of older men
      with depression over 6 years.
AB  - BACKGROUND: The concept of 'vascular depression' implies that cardiovascular
      disease facilitates the onset or persistence of depression in later life, and
      that the natural course of depression should differ according to whether or not
      vascular pathology is present. METHODS: Population-based cohort of 431 older men
      were diagnosed with depression (prevalent cases) and followed for up to 6 years.
      We used the Western Australian Data Linkage System to establish the presence of
      cardiovascular disease (CVD, documented history of coronary heart disease or
      stroke) and subsequent persistence or recurrence of depression during follow up
      (ICD-10 codes). Other measures recorded: age, place of birth, education, social
      support and disadvantage, smoking history, sensory impairment, medical morbidity
      burden and use of antidepressants. RESULTS: The age of participants ranged from
      69 to 86 years and CVD was present in 212 (49.2%) of them. Depressed men with and
      without CVD had a similar distribution of demographic, lifestyle, social and
      clinical factors as men without CVD, but higher medical morbidity. One hundred
      and twenty six (29.2%) men died and another 43 had a recorded diagnosis of
      depressive disorder between the baseline assessment and the 31st December 2007.
      Compared with participants without CVD, the adjusted hazard ratio of recurrent or
      persistent depression during follow up for participants with CVD was 0.78 (95%
      confidence interval, 95% CI=0.43-1.42). An additional 30 men were identified with
      depression during a new clinical assessment in 2008-09. Logistic regression
      showed that the adjusted odds of depression for men with compared to those
      without CVD was 0.98 (95% CI=0.61-1.59). CONCLUSION: Persistence or recurrence of
      symptoms over 6 years in older men with depression is not influenced by the
      presence of CVD, which raises doubts about the usefulness and validity of the
      concept of vascular depression.

PMID- 22858262
TI  - A preliminary open trial of nefazodone added to mood stabilizers for bipolar
      depression.
AB  - BACKGROUND: Little information exists on the use of nefazodone to treat bipolar
      depression. We hypothesized that nefazodone added to a standard mood stabilizer
      would show significant antidepressant efficacy with minimal agitation or
      induction of mania, by virtue of its selective 5-HT(2A) blockade. METHODS:
      Thirteen DSM-IV pure depressed-phase nonpsychotic bipolar outpatients received an
      open-label 8-week pilot trial of flexibly dosed nefazodone (mean+/-SD peak
      dose=462.5+/-164.0mg/day) with a concurrent mood stabilizer or atypical
      antipsychotic. Primary outcomes included the Hamilton Rating Scale for Depression
      (HAM-D) and Clinical Global Impressions Severity Scale (CGI-S). RESULTS: All
      subjects completed at least 4 weeks of treatment, while 9 (69%) completed the 8
      week protocol. Based on last observation point, 8 (62%) had at least a 50%
      reduction from baseline HAM-D scores. Significant improvement from baseline was
      observed in both HAM-D (z=2.05, p=.04) and CGI severity ratings (z=2.21, p=.03).
      Induction of mania occurred in 1 subject (7%). No subjects manifested clinical
      signs of hepatic failure, and none prematurely terminated the study due to other
      adverse events (most common side effects included fatigue, insomnia, nausea, or
      headache). LIMITATIONS: This was a small open-label pilot study with use of
      varied concomitant pharmacotherapies and no placebo comparator. CONCLUSIONS:
      While nefazodone is seldom used in clinical practice due to concerns about rare
      but severe hepatotoxicity, it may represent a model for postsynaptic 5HT(2A)
      antagonism that mechanistically could help to inform the development of future
      treatments for bipolar depression.

PMID- 22858263
TI  - A multilevel analysis of association between neighborhood social capital and
      depression: evidence from the first South African National Income Dynamics Study.
AB  - BACKGROUND: As neuropsychiatric disorders account for a great proportion of the
      total burden of disease in sub-Saharan Africa, depression is rapidly emerging as
      a public health issue in South Africa. Given the divisions enforced by a legacy
      of the apartheid spatial and economic policies, features of communities such as
      neighborhood-level social capital may play a critical role in depression.
      However, the extent to which neighborhood-level social capital is associated with
      depression in South Africa at the population-level is unknown. METHODS: Data from
      the first wave of the South African National Income Dynamics Study (SA-NIDS) was
      used to examine the association between the neighborhood-level social capital and
      individual depression using multilevel regression models. RESULTS: There was a
      negative association between neighborhood-level social capital and depression
      score with social trust and neighborhood preference accounting for this
      association. Structural social capital, namely civic participation, was not
      related to depression. Individual predictors, including social class, self-rated
      health status and education, were strong covariates of depression. LIMITATIONS:
      The cross-sectional design of the study limits our understanding of the temporal
      order of social capital and depression. CONCLUSIONS: In post-apartheid South
      Africa, low social capital remains an important social determinant of health,
      including depression outcome. This is in addition to individual determinants
      related to class such as unemployment, education and social class which play an
      important role in influencing depression. Further research utilizing a
      longitudinal study design is warranted to examine the association between social
      capital and depression in South Africa.

PMID- 22858264
TI  - A randomized, controlled, pilot study of dialectical behavior therapy skills in a
      psychoeducational group for individuals with bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BD) is a chronic and disabling psychiatric disorder
      characterized by recurrent episodes of mania/hypomania and depression.
      Dialectical behavior therapy (DBT) techniques have been shown to effectively
      treat borderline personality disorder, a condition also marked by prominent
      affective disturbances. The utility of DBT techniques in treating BD has been
      largely unexplored. The purpose of this research was to conduct a pilot study of
      a DBT-based psychoeducational group (BDG) in treating euthymic, depressed, or
      hypomanic Bipolar I or II patients. METHODS: In this experiment, 26 adults with
      bipolar I or II were randomized to intervention or wait-list control groups and
      completed the Beck depression inventory II, mindfulness-based self-efficacy
      scale, and affective control scale at baseline and 12 weeks. The BDG intervention
      consisted of 12 weekly 90-min sessions which taught DBT skills, mindfulness
      techniques, and general BD psychoeducation. RESULTS: Using RM-ANOVA, subjects in
      BDG demonstrated a trend toward reduced depressive symptoms, and significant
      improvement in several MSES subscales indicating greater mindful awareness, and
      less fear toward and more control of emotional states (ACS). These findings were
      supported with a larger sample of patients who completed the BDG. Furthermore,
      group attendees had reduced emergency room visits and mental health related
      admissions in the six months following BDG. LIMITATIONS: The small sample size in
      RCT affects power to detect between group differences. How well improvements
      after the12-week BDG were maintained is unknown. CONCLUSIONS: There is
      preliminary evidence that DBT skills reduce depressive symptoms, improve
      affective control, and improve mindfulness self-efficacy in BD. Its application
      warrants further evaluation in larger studies.

PMID- 22858265
TI  - Aberrant limbic and salience network resting-state functional connectivity in
      panic disorder without comorbidity.
AB  - BACKGROUND: Panic disorder (PD) is a prevalent and debilitating disorder but its
      neurobiology is still poorly understood. We investigated resting-state functional
      connectivity (RSFC) in PD without comorbidity in three networks that have been
      linked to PD before. This could provide new insights in how functional
      integration of brain regions involved in fear and panic might relate to the
      symptomatology of PD. METHODS: Eleven PD patients without comorbidity and eleven
      pair-wise matched healthy controls underwent resting-state fMRI. We used seed
      regions-of-interest in the bilateral amygdala (limbic network), the bilateral
      dorsal anterior cingulate cortex (dACC) (salience network), and the bilateral
      posterior cingulate cortex (default mode network). RSFC of these areas was
      assessed using seed-based correlations. All results were cluster corrected for
      multiple comparisons (Z>2.3, p<.05). RESULTS: Abnormalities were identified in
      the limbic network with increased RSFC between the right amygdala and the
      bilateral precuneus in PD patients. In the salience network the dACC demonstrated
      altered connectivity with frontal, parietal and occipital areas. LIMITATIONS: The
      small sample size and hypothesis-driven approach could restrict finding
      additional group differences that may exist. Other caveats are reflected in the
      use of medication by two participants and the acquisition of the resting-state
      scan at the end of a fixed imaging protocol. CONCLUSION: We found altered RSFC in
      PD between areas involved in emotion regulation and emotional and somatosensory
      stimulus processing, as well as an area engaged in self-referential processing,
      not implicated in models for PD before. These findings extend existing functional
      neuroanatomical models of PD, as the altered RSFC may underlie increased
      sensitivity for bodily symptoms.

PMID- 22858266
TI  - A systematic review of resting-state functional-MRI studies in major depression.
AB  - BACKGROUND: To evaluate the literature pertaining to the use of resting-state
      functional magnetic resonance imaging (fMRI) in Major Depression (MD). METHODS: A
      search for papers published in English was conducted using MedLine, Embase,
      PsycINFO, OvidSP, and ScienceDirect with the following words: resting state,
      depression, MRI, affective, and default-mode. RESULTS: The findings from 16
      resting-state fMRI studies on MD are tabulated. Some common findings are
      discussed in further detail. CONCLUSION: The use of resting-state fMRI in MD
      research has yielded a number of significant findings that provide the basis for
      understanding the pathophysiology of depressive symptoms. Of particular note and
      deserving of further research are the roles of the cortico-limbic mood regulating
      circuit (MRC) and the interaction between task-positive and task-negative
      networks in MD. There is increasing interest in the use of resting-state fMRI in
      the study of psychiatric conditions, and continued improvement in technique and
      methodology will prove valuable in future research.

PMID- 22858267
TI  - Grasses provide new insights into regulation of shoot branching.
AB  - Tillering (branching) is a major determinant of crop yield that is controlled by
      complex interactions between hormonal, developmental, and environmental factors.
      Historically, research on shoot branching has focused on eudicots, mainly due to
      the ease of manipulating branching by shoot decapitation and grafting in these
      species. These studies demonstrated hormonal control of branching. Recent studies
      in monocots have contributed to our knowledge of tillering/branching by
      identifying novel branching genes and regulatory mechanisms. A comparison of
      branching controls in eudicots and monocots reveals that the regulatory signals
      and genes are broadly conserved, but that there are differences in the detail.

PMID- 22858268
TI  - Rhizobium etli taxonomy revised with novel genomic data and analyses.
AB  - The taxonomic position of Phaseolus vulgaris rhizobial strains with available
      sequenced genomes was examined. Phylogenetic analyses with concatenated conserved
      genomic fragments accounting for over half of each genome showed that Rhizobium
      strains CIAT 652, Ch24-10 (newly reported genome) and CNPAF 512 constituted a
      well-supported group independent from Rhizobium etli CFN 42(T). DNA-DNA
      hybridization results indicated that CIAT 652, Ch24-10 and CNPAF 512 could
      correspond to R. etli, although the hybridization values were at the borderline
      that distinguishes different species. In contrast, experimental hybridization
      results were higher (over 80%) with Rhizobium phaseoli type strain ATCC 14482(T)
      in congruence to phylogenetic and ANIm analyses. The latter criterion allowed the
      reclassification of R. etli strains 8C-3 and Brasil5 as R. phaseoli. It was
      therefore concluded, based on all the evidence, that the CIAT 652, Ch24-10, and
      CNPAF 512 strains should be reclassified as R. phaseoli in spite of several
      common features linking them to R. etli. The R. phaseoli and R. etli speciation
      process seems to be a more recent event than the speciation that has occurred
      among other sister species, such as R. leguminosarum-R. etli or R. rhizogenes-R.
      tropici.

PMID- 22858269
TI  - Role of mitral valve plication in the surgical management of hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: We have previously reported our 3-step repair for obstructive
      hypertrophic cardiomyopathy (HCM) consisting of resection of the septum,
      horizontal plication of the anterior mitral leaflet (AML), and release of
      abnormal papillary muscle attachments. This article reviews our complete
      experience with surgical management of HCM to better understand the role and
      relevance of mitral plication. METHODS: From 1997 to 2011, 132 patients with HCM
      underwent surgical treatment at our institution. Eighty-two patients (62%)
      received AML plication based on selection criteria and were classified as group
      A; patients in group B did not receive plication. All patients underwent
      preoperative and postoperative echocardiography. Long-term clinical follow-up was
      obtained by review of scheduled echocardiograms and direct patient interview.
      RESULTS: The average age of all patients was 55.5 years. Operative mortality was
      0%. The mean left ventricular outflow tract (LVOT) gradient decreased from 118+/
      41 mm Hg to 6+/-13 mm Hg (p<0.0001). Mean mitral regurgitation improved from
      2.4+/-1.0 to 0.5+/-0.7 (p<0.0001). Postoperatively, 96.2% of patients had no
      residual systolic anterior motion (SAM). Significant improvements in heart
      failure classification and quality of life scores were noted for all patients.
      Comparison of groups A and B showed no statistically significant differences in
      outcomes, complications, or survival. Survival at 1, 5, and 10 years was 98%,
      98%, and 92%, respectively. CONCLUSIONS: The heterogeneity of the pathologic
      process in HCM supports detailed analysis of the septum, mitral leaflets, and
      subvalvular apparatus. Surgical management of HCM that includes horizontal
      plication of a lax and elongated AML is safe and results in durable clinical and
      echocardiographic improvement.

PMID- 22858270
TI  - Evaluation of pediatric near-infrared cerebral oximeter for cardiac disease.
AB  - BACKGROUND: Cerebral hypoxia-ischemia remains a complication in children with
      congenital heart disease. Near-infrared spectroscopy can be utilized at the
      bedside to detect cerebral hypoxia-ischemia. This study aimed to calibrate and
      validate an advanced technology near-infrared cerebral oximeter for use in
      children with congenital heart disease. METHODS: After institutional review board
      approval and parental consent, 100 children less than 12 years and less than 40
      kg were enrolled. Phase I (calibration) measured arterial and jugular venous
      saturation (SaO(2), SjO(2)) by co-oximetry simultaneously with device signals to
      calibrate an algorithm to determine regional cerebral saturation against a
      weighted average cerebral saturation (0.7 SjO(2) + 0.3 SaO(2)). Phase II
      (validation) evaluated regional cerebral saturation from the algorithm against
      the weighted average cerebral saturation by correlation, bias, precision, and
      A(Root Mean Square) assessed by linear regression and Bland-Altman analysis.
      RESULTS: Of 100 patients, 86 were evaluable consisting of 7 neonates, 44 infants,
      and 35 children of whom 55% were female, 79% Caucasian, and 41% with cyanotic
      disease. The SaO(2) and regional cerebral saturation ranged from 34% to 100% and
      34% to 91%, respectively. There were no significant differences in subject
      characteristics between phases. For the entire cohort, A(RMS), bias, precision,
      and correlation coefficient were 5.4%, 0.5%, 5.39%, and 0.88, respectively. Age,
      skin color, and hematocrit did not affect these values. CONCLUSIONS: This
      cerebral oximeter accurately measures the absolute value of cerebral saturation
      in children over a wide range of oxygenation and subject characteristics,
      offering advantages in assessment of cerebral hypoxia-ischemia in congenital
      heart disease.

PMID- 22858271
TI  - Tethering symmetry reflects advanced left ventricular mechanical dyssynchrony in
      patients with ischemic mitral regurgitation undergoing restrictive mitral valve
      repair.
AB  - BACKGROUND: We evaluated the papillary muscle systolic dyssynchrony (DYS-PAP)
      using two-dimensional speckle tracking echocardiography (2D-STE) in patients with
      chronic ischemic mitral regurgitation (CIMR) showing different preoperative
      leaflet pattern and investigated the impact of baseline tethering pattern in the
      prediction of significant post-repair desynchronized papillary muscle
      contraction. METHODS: We recruited 152 CIMR consecutive patients (64.4% male,
      mean age 65.9 +/- 7.1 years) who survived coronary artery bypass grafting (CABG)
      and (undersized mitral ring annuloplasty, performed between 2001and 2010. The
      assessment of DYS-PAP was performed preoperatively and at follow-up (median 41.5
      months [IQR 23-61]) by 2D-STE in the apical 4-chamber view for anterolateral
      papillary muscle and apical long-axis view for posteromedial papillary muscle).
      Based on the cutoff value (anterior-posterior tethering angle ratio alpha/beta >=
      0.76) patients were classified in 2 groups; symmetrical (group 1, n = 73, mean
      alpha/beta = 0.81 +/- 0.6) and asymmetrical preoperative tethering pattern (group
      2, n = 79, mean alpha/beta = 0.66 +/- 0.4). RESULTS: Recurrent MR occurred in
      67.1% (n = 49) in group 1 versus 3.8% (n = 3) in group 2 (p < 0.001). Comparing
      both groups at baseline, patients in group 1 had higher DYS-PAP (57.7 +/- 5.3 vs
      29.8 +/- 2.4 ms in group 2, p < 0.001) that significantly worsened at follow-up
      (78.1 +/- 8.8 ms, p < 0.001 versus baseline), whereas in group 2 it improved
      (26.6 +/- 6.0 ms, p < 0.001 versus baseline). Tethering symmetry significantly
      correlated with DYS-PAP (r = 0.90, p < 0.001) and it was a strong multivariable
      predictor of significant postoperative DYS-PAP (odds ratio 4.2; 95% confidence
      level 3.4 to 5.2, p < 0.001). CONCLUSIONS: Tethering symmetry is an easy and
      immediate tool to identify CIMR patients with advanced DYS-PAP who are unlikely
      to benefit from mitral repair with undersized mitral ring annuloplasty.

PMID- 22858272
TI  - Clinical outcomes of redo valvular operations: a 20-year experience.
AB  - BACKGROUND: A higher operative mortality rate has been reported after redo
      valvular procedures than after the primary operation. METHODS: Outcomes of 330
      consecutive patients undergoing 433 redo valvular operations at our institute
      during a 20-year period (January 1990 to December 2010) were reviewed
      retrospectively. The mean follow-up was 6.4 years (range, 0.05 to 1.3 years).
      Logistic regression analysis was used to identify factors associated with
      hospital death. RESULTS: The overall hospital mortality rate was 6.7% (29 of 433
      procedures). Logistic regression analysis identified only advanced New York Heart
      Association (NYHA) class as an independent predictor of hospital death. Overall
      survival at 5, 10, and 15 years was 83.6%+/-2.2%, 70.7%+/-3.4%, and 61.5%+/-4.5%,
      respectively. The 5-, 10-, and 15-year survivals for the first redo vs more than
      second redo groups were 86.5%+/-2.4% vs 74.7%+/-5.5%, 71.8%+/-3.9% vs 66.8%+/
      6.6%, and 60.2%+/-5.7% vs 63.1%+/-7.2%, respectively (log-rank P=0.505). The 5-
      and 10-year survivals for NYHA class I/II vs III/IV patients were 91.5%+/-2.1% vs
      70.4%+/-4.5% and 77.8%+/-4.1% vs 58.5%+/-5.6%, respectively (log-rank p<0.005).
      CONCLUSIONS: Redo valvular operation in NYHA class III/IV patients is associated
      with high hospital death and poor long-term survival. To achieve low hospital
      death and good long-term survival, redo operations, including more than third
      redo operations, should be performed in patients with lower NYHA class.

PMID- 22858273
TI  - Interim results of the 5-box thoracoscopic maze procedure.
AB  - BACKGROUND: In accordance with the Cox-Maze paradigm, successful treatment of
      atrial fibrillation (AF) requires (1) complete posterior left atrial isolation,
      (2) elimination of corridors for perimitral reentry, (3) elimination of cardiac
      venous (superior vena cava and coronary sinus) arrhythmogenic foci, (4) complete
      autonomic denervation, and (5) occlusion or removal of the left atrial appendage.
      Using a totally thoracoscopic approach, isolation of all left atrial
      arrhythmogenic substrate is achieved through the creation of 5 discrete but
      contiguous compartments, thereby enabling unambiguous verification with
      bidirectional block. Since no previous closed-chest procedure incorporates all
      these end points, an update on patient outcomes is reported. METHODS: One hundred
      seventy-nine consecutive patients with antiarrhythmic drug-resistant AF (3
      paroxysmal, 5 persistent, 171 longstanding persistent cases), known
      preoperatively for 5.7 (range 0.5 to 25) years, underwent the 5-box thoracoscopic
      Maze procedure. Only 1 patient suffered a serious procedural complication
      (sternotomy for pulmonary artery injury). Postoperative rhythm surveillance
      consisted of 1 week of continuous ambulatory monitoring at 3, 6, 13, and 24
      months. Failure was defined as any tachyarrhythmia exceeding 30 seconds beyond
      the 3-month anniversary. RESULTS: Freedom from AF was observed in 137 of 142
      patients at 3 months, 115 of 119 patients at 6 months, 75 of 78 patients at 13
      months, and 24 of 25 patients at 24 months. Two patients remain in sinus rhythm
      on low-dose antiarrhythmia therapy. Warfarin is discontinued only after the first
      monitoring session confirms rhythm stability. CONCLUSIONS: Replication of the
      left atrial Cox-Maze lesion set through a totally thoracoscopic approach isolates
      virtually all arrhythmogenic substrate. Meticulous verification of compartment
      integrity allows for outcomes equivalent to the Cox-Maze benchmark.

PMID- 22858274
TI  - Real-time complication monitoring in pediatric cardiac surgery.
AB  - BACKGROUND: As overall mortality rates have fallen in pediatric cardiac surgical
      procedures, complication monitoring is becoming an increasingly important metric
      of patient outcome. Currently there is no standardized method available to
      monitor severity-adjusted complications in congenital cardiac surgical
      procedures. METHODS: Complications associated with pediatric cardiac surgical
      procedures were prospectively collected from consecutive cases in a single
      pediatric cardiac surgical unit from October 1, 2009 to September 31, 2011.
      Complications were accounted for by frequency and severity and then stratified by
      surgical complexity, using the Risk Adjustment for Congenital Heart Surgery
      (RACHS) method, giving an average morbidity burden per RACHS category. "Expected"
      morbidity burden for each RACHS category was derived from year 1 (2009-2010)
      data. Observed minus expected (O:E) plots were then generated for the entire
      series of complications from year 2 (2010-2011) data. Separate O:E plots were
      also created for 5 complication classes and monitored for increases. RESULTS:
      There were 181 index surgical procedures performed in 178 patients. Two hundred
      and seventeen complications occurred in 80 procedures. The frequency and severity
      of complications increased with surgical complexity. The overall O:E plot was
      flagged twice for unanticipated increases in severity-adjusted complications.
      When the class-specific O:E plots were monitored for increases, the overall flags
      were found to originate from increased rates of infections and cardiac/operative
      complications. CONCLUSIONS: The O:E plot provides a simple and effective system
      to monitor complication rates over time based on severity-adjusted complication
      data. Grouping complications into classes allows us to identify specific subsets
      of complications that can be focused on to improve patient outcomes.

PMID- 22858275
TI  - Thromboembolic events before esophagectomy for esophageal cancer do not result in
      worse outcomes.
AB  - BACKGROUND: Esophageal cancer, chemotherapy, and radiation are all associated
      with an increased incidence of thromboembolic events (TEE). Development of a TEE
      during neoadjuvant treatment for esophageal cancer can alter the treatment
      course, as surgery may be delayed or cancelled because patients require
      anticoagulation therapy. We evaluated the incidence of preoperative TEE among
      esophageal cancer patients undergoing neoadjuvant treatment and the impact on
      morbidity, mortality, and timing of surgery. METHODS: We performed a
      retrospective review of a prospectively collected database of 1,057 patients who
      underwent esophagectomy for esophageal cancer between January 1999 and May 2010.
      Of these patients, 534 were treated with neoadjuvant chemotherapy and radiation.
      RESULTS: Preoperative thromboembolic events occurred in 75 of 534 patients
      (14.0%). The only preoperative factor associated with increased risk of TEE was
      increased preoperative weight (p=0.02). Fluorouracil significantly increased the
      risk of TEE (p=0.028, odds ratio 2.12, 95% confidence interval: 1.09 to 4.26),
      whereas there was no difference in patients receiving cisplatin (p=0.299). There
      was a trend toward an association between infectious complications during
      neoadjuvant therapy and TEE development (p=0.076). Patients with TEEs had a delay
      from neoadjuvant therapy to surgery (p=0.0004). The TEE group had a trend toward
      the increased onset of postoperative atrial fibrillation (p=0.0688, odds ratio
      1.77, 95% confidence interval: 0.96 to 3.27). There was no difference in
      respiratory complications (p=0.934), overall complications (p=0.859), 30-day
      mortality (p=0.899), or overall survival (p=0.790). CONCLUSIONS: Thromboembolic
      events in the preoperative period delay the time to surgery for patients with
      esophageal cancer. Despite this delay, there is no demonstrable effect on
      postoperative complications or mortality.

PMID- 22858276
TI  - Development and validation of a new outcome score in subglottic stenosis.
AB  - BACKGROUND: We prospectively evaluated a clinical and endoscopic score, the
      tracheal endoscopic clinical score (TECS), developed as a disease-specified
      outcome measure in adult patients undergoing operation for subglottic stenosis.
      We also performed a retrospective chart review to identify preoperative and
      intraoperative risk factors for worse TECS. METHODS: The TECS includes endoscopic
      (vocal cord and glottic function, anastomotic healing, and patency) and interview
      (respiration, voice, swallow) variables, and was administered at 6-month follow
      up. Endoscopic and subjective domains were weighted to obtain a continuous TECS
      index ranging from 0 (best) to 1 (worse). The TECS and preoperative variables
      relationships were evaluated by univariate and multivariate analysis. RESULTS: We
      collected data (January 2009 to December 2010) from 30 patients (mean age, 48.3+/
      19 years) undergoing subglottic resection and primary reconstruction. Stenosis
      etiology was postintubation (n=8), idiopathic (n=2), tracheostomy (n=18), and
      malignant (n=2). Surgery included Pearson operation with (n=7) or without (n=23)
      a Liberman-Mathisen cricoplasty. Mean length of resected trachea was 30.5+/-13.5
      mm, and mean hospital stay was 7.4 days. Mortality rate was 1 patient (3.3%). The
      univariate analysis showed positive correlation between 6-month TECS and degree
      of stenosis (McCaffrey and Cotton scale 0 to 4) stage 4, tracheostomy or T-tube
      at surgery, bottleneck-type transition stenosis, and resection length. At
      multivariate analysis, the presence of tracheostomy, bottleneck-type transition
      stenosis and resection length were indicators of worse postoperative functional
      result. CONCLUSIONS: The TECS seems to be a valid and simple instrument to
      identify preoperative variables predicting worse results and to assess
      postoperative outcome. Validation on larger series is necessary.

PMID- 22858277
TI  - Should patients 60 years and older undergo bridge to transplantation with
      continuous-flow left ventricular assist devices?
AB  - BACKGROUND: Although left ventricular assist devices (LVADs) are now commonly
      used as a bridge to orthotopic heart transplantation (OHT), the upper patient age
      limit for this therapy has not been defined. Smaller studies have suggested that
      advanced age should not be a contraindication to bridge to transplantation (BTT)
      LVAD placement. The purpose of this study was to examine outcomes in patients 60
      years and older undergoing BTT with continuous-flow LVADs. METHODS: The United
      Network for Organ Sharing (UNOS) database was reviewed to identify first-time OHT
      recipients 60 years of age and older (2005-2010). Patients were stratified by
      preoperative support: continuous-flow LVAD, intravenous inotropic agents, and
      direct transplantation. Survival after OHT was modeled using the Kaplan-Meier
      method. All-cause mortality was examined using multivariable Cox proportional
      hazard regression. RESULTS: Of 2,554 patients, 1,142 (44.7%) underwent direct
      transplantation, 264 (10.3%) had LVAD BTT, and 1,148 (45.0%) had BTT with
      inotropic agents. The mean age was 64+/-3 years, and 460 (18.0%) patients were
      women. Mean follow-up was 29+/-19 months. Survival differed significantly among
      the 3 groups. Patients with LVAD BTT had significantly lower survival after OHT
      compared with the other groups at 30 days and 1 year. This survival difference
      was no longer significant at 2 years after OHT or when deaths in the first 30
      days were censored. LVAD BTT increased the hazard of death at 1 year by 50%
      (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.05-2.15; p=0.03),
      compared with patients who underwent direct transplantation. CONCLUSIONS: This
      study represents the largest modern cohort in which survival after OHT has been
      evaluated in patients 60 years or older who received BTT. Older patients have
      lower short-term survival after OHT when BTT is carried out with a continuous
      flow LVAD compared with inotropic agents or direct transplantation.

PMID- 22858278
TI  - Longitudinal outcome of isolated mitral repair in older patients: results from
      14,604 procedures performed from 1991 to 2007.
AB  - BACKGROUND: Mitral valve (MV) repair is performed with less frequency than MV
      replacement in older persons, with referral often delayed until symptoms are
      severe. Surgical practice in this population remains inconsistent in the absence
      of national MV repair outcomes. The goal of this study was to assess durability
      and longitudinal outcomes after isolated primary MV repair in patients aged 65
      years or more. METHODS: We linked clinical data from The Society of Thoracic
      Surgeons adult cardiac surgery database (STS) to longitudinal claims data from
      the Centers for Medicare and Medicaid Services (CMS). Between January 1991 and
      December 2007, we identified 14,604 isolated nonemergent primary MV repair
      operations in STS-CMS data. These were longitudinally examined for mortality,
      mitral reoperation, and readmissions for heart failure, bleeding, and stroke.
      Predictors of 5-year death after MV repair were identified using Cox proportional
      hazard modeling. RESULTS: The study cohort had a mean age of 73.3+/-5.5 years,
      ejection fraction 54.0%+/-12.9%; 55.8% (8,148 of 14,604) were female; and 8.4%
      (1,233 of 14,604) were non-Caucasian. Operative mortality was 2.59% (378 of
      14,604). Mean follow-up was 5.9+/-3.9 years (range, 1.0 to 18.0). Survival during
      follow-up was 74.9% (10,934 of 14,604). The number of observed events for mitral
      reoperation, heart failure, bleeding, and stroke were 552 of 14,604 (3.7%), 2,681
      of 14,604 (18.4%), 1,051 of 14,604 (7.2%), and 1,131 of 14,604 (7.7%),
      respectively. The 10-year Kaplan-Meier event rates for mitral reoperation, heart
      failure, bleeding, and stroke were 6.2%, 30.1%, 15.3%, and 16.4%, respectively.
      The 10-year actuarial survival of 57.4% was equivalent to the matched US
      population. CONCLUSIONS: Utilizing linked STS and CMS databases, we demonstrate
      that MV repair is a safe and durable long-term option for older patients.
      Survival restored to the normal population suggests repair may suppress the
      longitudinal impact of mitral regurgitation in the elderly and that the practice
      of delayed referral should be reevaluated. These data provide a contemporary
      longitudinal benchmark of MV repair outcomes.

PMID- 22858279
TI  - Management of giant congenital pulmonary airway malformations requiring
      pneumonectomy.
AB  - BACKGROUND: Congenital pulmonary airway malformation (CPAM) is a rare congenital
      anomaly that occurs sporadically throughout fetal development. CPAM is usually a
      lobar process, but involvement of an entire lung is exceedingly rare. We present
      a small series of patients with multilobar CPAM who, to the best of our
      knowledge, are the first reported cases of giant CPAMs treated with pneumonectomy
      at birth. METHODS: After institutional review board approval, 93 medical records
      were reviewed for infants 0 to 12 months with congenital cystic adenomatoid
      malformation (CCAM) from 1990 to 2011. Three patients with entire lung
      involvement were included. RESULTS: Two patients were identified prenatally by
      ultrasonography and 1 was diagnosed at birth. Prenatally, the 2 patients
      exhibited mediastinal shift and steroids were administered. A pericardial
      effusion and decreased movement developed in 1 patient, requiring an emergent
      cesarean section at 31 weeks' gestation. All 3 patients underwent immediate
      newborn resection. One infant went into cardiac arrest on delivery and was
      resuscitated and taken for emergent resection. The 2 patients delivered vaginally
      at term tolerated spontaneous ventilation without positive pressure. All 3
      patients underwent an emergent pneumonectomy on the first day of life. The
      premature infant died intraoperatively after CPAM removal from severe pulmonary
      hypertension (HTN) and contralateral lung hypoplasia. The hospital course for
      these patients was characterized by prolonged stays in the intensive care unit
      (ICU), pneumonia, ventilator dependence, and pulmonary HTN. Bronchoscopy revealed
      tracheomalacia in 1 patient that was relieved by aortopexy; the other patient had
      bronchomalacia requiring tracheotomy. CONCLUSIONS: Emergent total pneumonectomy
      can be lifesaving, although significant pulmonary HTN can be expected. Management
      options may include fetal surgical intervention, ex utero intrapartum treatment
      (EXIT), and expectant management. Extracorporeal membrane oxygenation (ECMO), a
      prolonged ICU course, and symptomatic tracheomalacia/bronchomalacia may be
      anticipated. Families can be counseled that survival is achievable with adequate
      contralateral lung development.

PMID- 22858280
TI  - Inflow typology and ventricular geometry determine efficiency of filling in the
      hypoplastic left heart.
AB  - BACKGROUND: Pediatric patients with hypoplastic left heart syndrome rely solely
      on the right ventricle, resulting in anatomic maladaptations that can
      significantly compromise diastolic efficiency and lead to heart failure. Clinical
      indices to evaluate diastole are generally derived from the adult left ventricle,
      limiting their relevance to patients with hypoplastic left heart syndrome. We
      investigated the effect of the ventricular cavity shape and tricuspid inflow
      typology on the filling dynamics to provide new directions of investigation for
      assessing diastolic function in these patients. METHODS: Magnetic resonance
      imaging data were used to generate personalized mathematic models of 4 patients
      with different prognoses after stage I of the Norwood procedures. Two of these
      patients were also modeled after stage II. Numeric simulations were performed to
      analyze the interaction between blood flow and the myocardium during diastole.
      RESULTS: The filling dynamics were characterized by the formation of an organized
      structure of swirling blood (vortex ring). This was strongly influenced by the
      ventricular shape and the timing of the E and A wave. Biphasic rather than fused
      inflows and more elliptical than spherical cavities were found to increase the
      intraventricular pressure gradients and the filling capacity by optimizing the
      energy transfer between blood flow and the myocardium. This resulted in a better
      flow propagation and higher tissue velocities and displacements. CONCLUSIONS: The
      variations in the kinetic energy associated with the blood motion reflected the
      base-to-apex pressure difference and can therefore be used to quantify the
      efficiency of filling, providing a potential new metric to assess diastolic
      function in these patients.

PMID- 22858281
TI  - Anthelmintic cyclcooctadepsipeptides: complex in structure and mode of action.
AB  - The broad-spectrum anthelmintic cyclooctadepsipeptide PF1022A is a fungal
      metabolite from Rosellinia sp. PF1022, which is a Mycelia sterilia found on the
      leaves of Camellia japonica. A broad range of structurally related
      cyclooctadepsipeptides has been characterized and tested for anthelmintic
      activities. These metabolites have been used as starting points to generate
      semisynthetic derivatives with varying nematocidal capacity. Predominant among
      these compounds is emodepside, which exhibits a broad nematocidal potential
      against gastrointestinal and extraintestinal parasites. Here we review the
      chemical biology and mode of action of cyclooctadepsides with particular
      attention to PF1022A and emodepside. We illustrate how they target nematode
      neuromuscular function, opening up new avenues for antiparasitic treatments with
      potential capability for important selective toxicity.

PMID- 22858282
TI  - Characterization of turbidity in Florida's Lake Okeechobee and Caloosahatchee and
      St. Lucie estuaries using MODIS-Aqua measurements.
AB  - This paper describes the use of ocean color remote sensing data from the Moderate
      Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua satellite to
      characterize turbidity in Lake Okeechobee and its primary drainage basins, the
      Caloosahatchee and St. Lucie estuaries from 2002 to 2010. Drainage modification
      and agricultural development in southern Florida transport sediments and
      nutrients from watershed agricultural areas to Lake Okeechobee. As a result of
      development around Lake Okeechobee and the estuaries that are connected to Lake
      Okeechobee, estuarine conditions have also been adversely impacted, resulting in
      salinity and nutrient fluctuations. The measurement of water turbidity in
      lacustrine and estuarine ecosystems allows researchers to understand important
      factors such as light limitation and the potential release of nutrients from re
      suspended sediments. Based on a strong correlation between water turbidity and
      normalized water-leaving radiance at the near-infrared (NIR) band (nL(w)(869)), a
      new satellite water turbidity algorithm has been developed for Lake Okeechobee.
      This study has shown important applications with satellite-measured nL(w)(869)
      data for water quality monitoring and measurements for turbid inland lakes. MODIS
      Aqua-measured water property data are derived using the shortwave infrared (SWIR)
      based atmospheric correction algorithm in order to remotely obtain synoptic
      turbidity data in Lake Okeechobee and normalized water-leaving radiance using the
      red band (nL(w)(645)) in the Caloosahatchee and St. Lucie estuaries. We found
      varied, but distinct seasonal, spatial, and event driven turbidity trends in Lake
      Okeechobee and the Caloosahatchee and St. Lucie estuary regions. Wind waves and
      hurricanes have the largest influence on turbidity trends in Lake Okeechobee,
      while tides, currents, wind waves, and hurricanes influence the Caloosahatchee
      and St. Lucie estuarine areas.

PMID- 22858283
TI  - Renovation activities during pregnancy induce a Th2 shift in fetal but not in
      maternal immune system.
AB  - The aim of the present study was to investigate to which extent environmental
      influences like indoor renovation activities affect the immune system of mother
      and child during the gestation period. Within the LINA (Lifestyle and
      Environmental Factors and their Influence on Newborn Allergy risk) birth cohort
      study blood samples of mothers during pregnancy and cord blood samples were
      analyzed for concentrations of the Th1/Th2 cytokines IL-4, IL-5, IL-13, IFN-gamma
      and IgE. Data on indoor renovation activities (painting, flooring and new
      furniture) were assessed with questionnaires. Data on cytokine blood
      concentrations and exposure variables were available for 422 mother/child pairs.
      Neonates, who were strongly affected by renovation activities (especially floor
      covering and new furniture) during pregnancy, had significantly higher
      concentrations of IL-4 and IL-5 in cord blood. Among the single activities, new
      furniture, particularly flake board, were associated with increased IL-4 levels.
      Elevated IL-4 levels were also observed in the cord blood of children whose
      mothers reported wall-to-wall carpeting. Among flooring, polyvinylchloride (PVC)
      showed the strongest effect with increased IL-5 concentrations. The Th1/Th2
      imbalance towards Th2 at birth was related to allergic sensitization in children
      at the age of one. There were only few and negative associations between
      renovation activities and Th1/Th2 cytokine concentration in maternal blood. Our
      study shows that under similar exposure situations the fetal immune system is
      more susceptible to the influence of environmental factors, in particular
      renovation products (flake board, wall-to-wall carpets and PVC) compared to the
      maternal.

PMID- 22858284
TI  - Atherosclerotic disease in octogenarians: a challenge for science and clinical
      practice.
AB  - Besides the time of exposure to the traditional risk factors, new players take
      the lead in the modulation of atherogenesis in the very elderly, promoting a step
      increase in the incidence of cardiovascular events. Accordingly, atherosclerotic
      plaques become more abundant and portray more unstable features, such as
      increased inflammatory activity and reduction of smooth muscle cells in the very
      elderly. This new scenario is composed of new potential modulators of
      atherogenesis such as cellular senescence, immunosenescence, frailty syndrome,
      sarcopenia and sirtuins, and changes among the traditional cardiovascular risk
      factors which gain new attributes and new magnitudes of interaction with
      atherosclerotic disease. Consistent with this concept, mortality from
      atherosclerotic disease has shown a decrease in individuals younger than 60
      years, but no change in incidence in individuals over the age of 60 years. In
      this review, we present the most recent and relevant pieces of evidence to the
      peculiarities of traditional cardiovascular risk factors and new aging-related
      potential modulators of atherosclerotic disease in very elderly.

PMID- 22858285
TI  - Abnormal lipoprotein particles and cholesterol efflux capacity in patients with
      psoriasis.
AB  - OBJECTIVES: Psoriasis is a Th-1/17 mediated inflammatory disease associated with
      increased risk of cardiovascular disease (CVD). Inflammation may modulate
      lipoprotein particle number and directly impair HDL functions, in particular
      reverse cholesterol transport (RCT). We sought to study how chronic in vivo
      inflammation modulates lipoprotein particle composition using nuclear magnetic
      resonance spectroscopy (NMR) and HDL efflux in psoriasis. METHODS AND RESULTS: We
      prospectively enrolled a consecutive sample of patients with psoriasis (n = 122)
      and compared lipoprotein and metabolic risk factors to patients without psoriasis
      (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and
      lipoprotein concentration and size were measured by NMR. In a random subset (n =
      100 each group), HDL efflux capacity was quantified using a validated ex vivo
      system involving the incubation of macrophages with apolipoprotein B-depleted
      serum from patients. Traditional lipid concentrations were similar in both groups
      except for HDL concentration which was lower in psoriasis (43 mg/dl (36-58) vs 50
      (42-62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis
      similar to that observed in diabetes, with significant increase in LDL particle
      concentration [1210.5 (1002-1498) vs 1115 (935-1291), p = 0.02] with decrease in
      LDL size [20.6 (20.3-21.1) vs 21.3 (20.6-21.1), p < 0.001] beyond CV risk factors
      and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis
      compared to controls in fully adjusted models (beta -0.14, p = 0.001).
      CONCLUSIONS: These data support a more atherogenic lipoprotein profile by NMR and
      decreased HDL efflux capacity in psoriasis patients compared to controls beyond
      CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux
      capacity in psoriasis may provide a link between psoriasis and CVD.

PMID- 22858286
TI  - Cellular growth factors in relation to mortality from cardiovascular disease in
      middle-aged Japanese: the JACC study.
AB  - OBJECTIVE: Limited evidence has been available on the relationships of cellular
      growth factors with cardiovascular disease in population-based samples. METHODS:
      We conducted a nested case-control study under a large prospective cohort study
      (JACC study) where a total of 39,242 subjects aged 40-79 years provided serum
      sample. We measured cellular growth factors [insulin-like growth factors I, II
      and binding protein-3 (IGF-I, IGF-II and IGFBP-3) and transforming growth factor
      (TGF-beta1)] among cases and controls, matched for sex, age, area of residence
      and year of serum storage. RESULTS AND CONCLUSIONS: During the follow-up for 9
      years, there were 233 deaths from total stroke (49 subarachnoid hemorrhages, 55
      intraparenchymal hemorrhages, 71 ischemic strokes), and 97 deaths from coronary
      heart disease. The multivariable odds ratio (95%CI) of intraparenchymal
      hemorrhage associated with a 1-SD increment of IGF-I (men:4 8 ng/ml, women: 61
      ng/ml) was 0.31 (0.14-0.71). That of ischemic stroke associated with a 1-SD
      increment of TGF-beta1 (men: 8.0 ng/ml, women: 10.9 ng/ml) was 0.58 (0.34-0.98).
      Serum IGF-II and IGFBP-3 were not associated with mortality from any outcomes. In
      conclusion, IGF-I was inversely associated with mortality from intraparenchymal
      hemorrhage while TGF-beta1 was so with ischemic stroke, suggesting potential
      roles of cellular proliferation in the development or prognosis of stroke.

PMID- 22858287
TI  - Independent and incremental role of quantitative right ventricular evaluation for
      the prediction of right ventricular failure after left ventricular assist device
      implantation.
AB  - OBJECTIVES: This study sought to determine the utility of quantitation of right
      ventricular (RV) function in predicting RV failure in patients undergoing left
      ventricular assist device (LVAD) implantation. BACKGROUND: Clinical evaluation
      alone seems insufficient for predicting RV failure, an important cause of
      morbidity and mortality after LVAD implantation. METHODS: Clinical, hemodynamic,
      and echocardiographic data were collected on 117 patients undergoing LVAD
      implantation. Standard pre-procedural echocardiographic RV measurements were
      supplemented by velocity vector imaging of RV free wall longitudinal strain. RV
      failure was defined as the need for placement of an RV assist device, or the use
      of inotropic agents for >14 days. Receiver operating characteristic curves were
      derived, with resampling to generate valid estimates of prediction accuracy. A
      net reclassification index was calculated for comparison of risk scores. RESULTS:
      RV failure occurred in 47 of 117 patients (40%). There was a significant
      difference in peak strain between patients with and without RV failure (-9.0% vs.
      -12.2%; p < 0.01). A peak strain cutoff of -9.6% predicted RV failure with 76%
      specificity and 68% sensitivity. In a multivariate logistic regression analysis
      including variables from the established Michigan RV risk score, peak strain
      remained an independent predictor of RV failure. RV strain was incremental to the
      Michigan risk score as a predictor of RV failure (area under the receiver
      operating characteristic curve: 0.77 vs. 0.66; p < 0.01). The net
      reclassification index with strain was +10.4%. CONCLUSIONS: Reduced RV free wall
      peak longitudinal strain was associated with an increased risk for RV failure
      among patients undergoing LVAD implantation.

PMID- 22858288
TI  - The right prediction.

PMID- 22858289
TI  - Does the left atrial appendage morphology correlate with the risk of stroke in
      patients with atrial fibrillation? Results from a multicenter study.
AB  - OBJECTIVES: This study investigated the left atrial appendage (LAA) by computed
      tomography (CT) and magnetic resonance imaging (MRI) to categorize different LAA
      morphologies and to correlate the morphology with the history of stroke/transient
      ischemic attack (TIA). BACKGROUND: LAA represents one of the major sources of
      cardiac thrombus formation responsible for TIA/stroke in patients with atrial
      fibrillation (AF). METHODS: We studied 932 patients with drug-refractory AF who
      were planning to undergo catheter ablation. All patients underwent cardiac CT or
      MRI of the LAA and were screened for history of TIA/stroke. Four different
      morphologies were used to categorize LAA: Cactus, Chicken Wing, Windsock, and
      Cauliflower. RESULTS: CT scans of 499 patients and MRI scans of 433 patients were
      analyzed (age 59 +/- 10 years, 79% were male, and 14% had CHADS(2) [Congestive
      heart failure, hypertension, Age >75, Diabetes mellitus, and prior stroke or
      transient ischemic attack] score >=2). The distribution of different LAA
      morphologies was Cactus (278 [30%]), Chicken Wing (451 [48%]), Windsock (179
      [19%]), and Cauliflower (24 [3%]). Of the 932 patients, 78 (8%) had a history of
      ischemic stroke or TIA. The prevalence of pre-procedure stroke/TIA in Cactus,
      Chicken Wing, Windsock, and Cauliflower morphologies was 12%, 4%, 10%, and 18%,
      respectively (p = 0.003). After controlling for CHADS2 score, gender, and AF
      types in a multivariable logistic model, Chicken Wing morphology was found to be
      79% less likely to have a stroke/TIA history (odd ratio: 0.21, 95% confidence
      interval: 0.05 to 0.91, p = 0.036). In a separate multivariate model, we entered
      Chicken Wing as the reference group and assessed the likelihood of stroke in
      other groups in relation to reference. Compared with chicken wing, cactus was
      4.08 times (p = 0.046), Windsock was 4.5 times (p = 0.038), and Cauliflower was
      8.0 times (p = 0.056) more likely to have had a stroke/TIA. CONCLUSIONS: Patients
      with Chicken Wing LAA morphology are less likely to have an embolic event even
      after controlling for comorbidities and CHADS2 score. If confirmed, these results
      could have a relevant impact on the anticoagulation management of patients with a
      low-intermediate risk for stroke/TIA.

PMID- 22858290
TI  - Left main coronary artery compression associated with primary pulmonary
      hypertension.

PMID- 22858291
TI  - The heart of the matter: Why the ACC has an international outreach.

PMID- 22858292
TI  - Clinical valve of myocardial contrast delayed enhancement with multidetector
      computed tomography.

PMID- 22858295
TI  - The predictive value of plasma neutrophil gelatinase-associated lipocalin on
      cardiovascular death and all-cause mortality might be mediated by leukocytosis.

PMID- 22858296
TI  - Transcatheter aortic valve replacement with coronary artery protection performed
      in a patient with an anomalous left main coronary artery.

PMID- 22858297
TI  - Leishmanicidal activities and cytotoxicities of bisnaphthoquinone analogues and
      naphthol derivatives from Burman Diospyros burmanica.
AB  - A methanol extract of the wood of Diospyros burmanica, collected in Burma
      (Myanmar), was found to exhibit significant activity against Leishmania major.
      Subsequent chromatographically resolved fractionation led to the isolation of
      three novel bisnaphthoquinone analogues, burmanin A, B, and C (1-3), together
      with nine known compounds (4-12). The structure of 1 was confirmed by X-ray
      crystallography, and those of 2 and 3 by spectroscopic techniques, including 1D
      and 2D NMR. The inhibitory activities of the isolates were evaluated against the
      promastigote forms of Leishmania major and the murine macrophage-like cell line,
      RAW264.7.

PMID- 22858298
TI  - Synthesis, cytotoxic and antioxidant evaluations of amino derivatives from
      perezone.
AB  - A series of eight amino derivatives (3a-h) from perezone 1 were prepared by
      nucleophilic addition of bioactive amines v.gr. melatonin, acetyl tryptamine,
      tryptophan and other amino acids esters (valine, leucine and methionine). Their
      structures were elucidated by spectroscopy data. The cytotoxic evaluation against
      four human tumor cell lines PC-3, K-562, HCT-15 and SKLU-1 was performed as well
      as the TBARS assay for antioxidant activity. The results suggest that 1 and its
      isomer 4 were highly active against all cell lines, 4 was twice as potent than 1
      against PC-3 and HCT-15. The derivative 3a (IC(50)=7.5 +/- 0.3 MUM) was more
      active than 1 against HCT-15 whereas 3h was selective against K-562 with
      IC(50)=4.5 +/- 0.4 MUM. The TBARS assay has shown that 3c with IC(50)=5.564 +/-
      0.24 MUM is a potent antioxidant with superior effect comparing to alpha
      tocopherol and moreover was more active than the precursor molecule 1.

PMID- 22858299
TI  - Synthesis of sulfur containing dihydro-pyrrolo derivatives and their biological
      evaluation as antioxidants.
AB  - The 1,3-dipolar cycloaddition to N-phenylmaleimide of azomethine ylides,
      generated in situ from sulfanyl-substituted imines of glycine esters, yields 5H
      dihydro-pyrrolo products with syn diastereoselectivity. The syn (major) and anti
      (minor) products were isolated chromatographically and fully characterized by
      spectroscopic methods and in two cases also by X-ray analysis. The diastereomeric
      cycloadducts were tested for their antioxidant activity with good results.

PMID- 22858300
TI  - Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria
      combination therapy.
AB  - Malaria and HIV are among the most important global health problems of our time
      and together are responsible for approximately 3 million deaths annually. These
      two diseases overlap in many regions of the world including sub-Saharan Africa,
      Southeast Asia and South America, leading to a higher risk of co-infection. In
      this study, we generated and characterized hybrid molecules to target Plasmodium
      falciparum and HIV simultaneously for a potential HIV/malaria combination
      therapy. Hybrid molecules were synthesized by the covalent fusion of
      azidothymidine (AZT) with dihydroartemisinin (DHA), a tetraoxane or a 4
      aminoquinoline derivative; and the small library was tested for antiviral and
      antimalarial activity. Our data suggests that compound 7 is the most potent
      molecule in vitro, with antiplasmodial activity comparable to that of DHA
      (IC(50)=26 nM, SI>3000), a moderate activity against HIV (IC(50)=2.9 MUM; SI>35)
      and not toxic to HeLa cells at concentrations used in the assay (CC(50)>100 MUM).
      Pharmacokinetics studies further revealed that compound 7 is metabolically
      unstable and is cleaved via O-dealkylation. These studies account for the lack of
      in vivo efficacy of compound 7 against the CQ-sensitive Plasmodium berghei N
      strain in mice, when administered orally at 20mg/kg.

PMID- 22858301
TI  - Application of the Knowledge-to-Action and Medical Research Council frameworks in
      the development of an osteoporosis clinical decision support tool.
AB  - OBJECTIVE: Informatics-based knowledge translation interventions have the
      potential to address clinical practice and patient care, but evidence shows that
      they can fail, have the potential to be ineffective, function poorly, and result
      in medical or technology-induced errors if rushed to become an integral part of
      health care systems and practices. In an attempt to meet these challenges and
      advance the science of developing knowledge translation interventions, the
      objective of this study was to apply two theoretical frameworks (the Knowledge-to
      Action and the Medical Research Council frameworks for complex interventions) in
      the development of an osteoporosis clinical decision support tool. STUDY DESIGN
      AND SETTING: Descriptive analysis of how the Knowledge-to-Action and Medical
      Research Council frameworks can be applied in the development of an osteoporosis
      tool. RESULTS: An osteoporosis tool was developed using a seven-phase process by
      collapsing the "action" steps of the Knowledge-to-Action cycle and phases of the
      Medical Research Council framework. Analysis of this procedure informed a
      proposed seven-step process that may be applied by others in the development of
      knowledge translation tools and complex interventions. CONCLUSIONS: The combined
      frameworks can be used to map the process for translating evidence into practice
      by addressing potential barriers, and anticipating how knowledge will be
      sustained and disseminated.

PMID- 22858302
TI  - Interstitial pneumonitis secondary to eprosartan.

PMID- 22858303
TI  - High incidence of bloodstream infection due to gram-negative bacilli in patients
      with pulmonary hypertension receiving intravenous treprostinil.
AB  - INTRODUCTION: An excessive risk for bacteremia has recently been reported in
      patients with pulmonary arterial hypertension (PAH) treated with intravenous
      treprostinil. We aimed to assess this association in a cohort of patients from a
      Spanish referral center. PATIENTS AND METHODS: We performed a retrospective
      cohort study that included 55 patients diagnosed with PAH who received a
      continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil)
      for >=1month at our center between January 1991 and December 2011. The risk
      factors associated with the incidence of bacteremia were analyzed with the log
      rank test. RESULTS: After a total follow-up of 64,453 treatment days, we found 12
      episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram
      negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and
      Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118
      episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938
      episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037).
      All episodes of bacteremia due to Gram-negative bacilli were diagnosed in
      patients on treprostinil. In the univariate analysis the treatment with
      intravenous treprostinil was associated with the incidence of bacteremia (hazard
      ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of
      events prevented us from performing a multivariate analysis. CONCLUSIONS: Therapy
      with intravenous treprostinil is associated with a higher risk for bacteremia,
      especially due to non-fermenting Gram-negative bacilli. This association should
      be taken in consideration when choosing empirical antibiotic therapy for patients
      with PAH and sepsis.

PMID- 22858304
TI  - Purification and differential biological effects of ginger-derived substances on
      normal and tumor cell lines.
AB  - This study describes an optimization of [6]-, [8]- and [10]-gingerol isolation
      and purification in semi-preparative HPLC scale and their anti-proliferative
      activity. The gingerols purification was carried out in HPLC system using a Luna
      C18 and the best mobile phase evaluated was MeOH/H2O (75:25, v/v). This new
      methodology for the gingerols isolation was very effective, since considerable
      amounts (in the range of milligrams) with a good purity degree (~98%) were
      achieved in 30 min of chromatographic run. [6]-, [8]- and [10]-Gingerol purified
      by this methodology inhibited the proliferation of MDA-MB-231 tumor cell line
      with IC50 of 666.2+/-134.6 MUM, 135.6+/-22.6 MUM and 12.1+/-0.3 MUM,
      respectively. These substances also inhibited human fibroblasts (HF) cell
      proliferation, however in concentrations starting from 500 MUM. In conclusion,
      our results demonstrate an optimization of gingerols isolation and their specific
      anti-proliferative activities against tumor cells, suggesting their use as
      important models for drug design in an attempt to develop new compounds with
      fewer side effects when compared to conventional chemotherapy.

PMID- 22858305
TI  - Hochschild (2003) - the managed heart: the recognition of emotional labour in
      public service work.

PMID- 22858306
TI  - The effects of a deliberate practice program on nursing students' perception of
      clinical competence.
AB  - BACKGROUND: New nursing graduates' readiness for practice often does not meet the
      requirements needed in the real situation of clinical sites. Therefore, nurse
      education has placed more emphasis on developing students' technical skills to
      cultivate proficiencies needed for clinical sites. OBJECTIVES: To develop a
      program including deliberate skill practices and technical skill testing, each
      conducted before students' clinical practicum, and to examine the program's
      effects on nursing students' clinical competence. DESIGN: The study was a
      repeated measure correlational design. SETTINGS: One nursing university.
      PARTICIPANTS: Two-hundred-fifty-six and 266 nursing students in a RN-to-BSN night
      school program in Taiwan completed pretest and posttest surveys, respectively in
      2009 and 2010. Their mean age was 22.61 years and had worked 12.75 months as a
      nurse. METHODS: Students were asked to participate in the deliberate nursing
      practice program, which includes skill practice and tests, before their last
      clinical practicum. The Clinical Competence Questionnaire was used to measure the
      outcome of deliberate practice. RESULTS: Findings indicated that participants who
      had nursing work experience, a higher grade point average, practiced their skills
      by watching videos, and higher pretest competence scores exhibited significantly
      higher posttest competence scores. Participants who worked in the operating
      room/outpatient department, scored higher on self-confidence in clinical
      performance, and had a higher level of future job stress exhibited significantly
      lower posttest competence scores. CONCLUSIONS: Although work experience increased
      clinical competence, working in the operating room/outpatient department where
      many nursing skills were not performed did not have the effects. In contrast,
      skill reviews and better performance before practice promoted competence.
      Attaining motor skill competency is a slow process requiring practices. Thus,
      providing deliberate skill-practice program is suggested to help students
      increase their competence.

PMID- 22858307
TI  - Culturally diverse health care students' experiences with teaching strategies in
      Finland: a national survey.
AB  - BACKGROUND: All over the world, current health care students come from a variety
      of cultural, linguistic and educational backgrounds. Their expectations and
      learning needs vary, yet little is known about how our current education system
      meets their needs. OBJECTIVES: The purpose of this study was to explore
      culturally diverse health care students' experiences of teaching strategies in
      polytechnic faculties of health care in Finland. Specifically, we aimed to
      compare how international students and Finnish students experience the same
      curriculum. DESIGN: A cross sectional survey. SETTINGS: Ten polytechnic faculties
      of health care in Finland offering English-Language-Taught Degree Programmess
      (ELTDPs). PARTICIPANTS: 283 students studying nursing, public health nursing, or
      physiotherapy in English. Of these, 166 were international students and 112 were
      Finnish students. METHODS: The data were collected using a questionnaire designed
      specifically for this study. The survey included items grouped into seven
      dimensions: 1. concreteness of theoretical instruction, 2. encouragement of
      student activity, 3. use of skills labs, 4. variation among teaching strategies,
      5. assessment, 6. interaction in the English-Language-Taught Degree Programmes,
      and 7. approach to diversity in the English-Language-Taught Degree Programmes.
      RESULTS: The most positive experiences for all students were with the approach to
      cultural diversity and the concreteness of theoretical instruction, whereas the
      most negative experiences were with assessment. International students'
      experiences were more positive than Finnish students' in the following
      dimensions: encouragement of student activity (p=0.005), variation among teaching
      strategies (p<0.001), and assessment (p<0.001). Compared to the Finnish students,
      more than double the number of international students were dissatisfied with
      their lives (p<0.001). CONCLUSIONS: The implications for education include the
      strengthening teachers' leadership role in small group activities, providing
      individual and detailed feedback, and ensuring appropriate support mechanisms for
      all students.

PMID- 22858308
TI  - Temporal trends in pre-surgical evaluations and epilepsy surgery in the U.S. from
      1998 to 2009.
AB  - OBJECTIVE: To analyze trends in utilization of pre-surgical evaluations including
      video-EEG (VEEG) monitoring, intracranial EEG (IEEG) monitoring, and epilepsy
      surgery from 1998 to 2009 in the U.S. METHODS: Data from the Nationwide Inpatient
      Sample were used to identify admissions for pre-surgical evaluations and surgery.
      Surgical treatment of epilepsy was identified by the presence of primary ICD-9-CM
      procedure codes 01.52 (hemispherectomy), 01.53 (lobectomy), or 01.59 (other
      excision of the brain, including amygdalohippocampectomy). We calculated annual
      rates of pre-surgical evaluations and surgery based on published estimates of
      prevalence of epilepsy in the U.S. In addition, we examined variations by region
      and hospital characteristics, and conducted multivariable analysis to detect
      temporal trends, adjusting for changes in the population. Sensitivity analysis
      was also conducted using different algorithms to identify the study population
      and outcomes. RESULTS: We detected an increase in the rate of hospitalizations
      related to intractable epilepsy. Similarly, we noted a significant increase in
      hospitalizations for VEEG monitoring, but not in IEEG monitoring or in surgery.
      Multivariable analysis and sensitivity analysis confirmed these results. In
      addition, there was a significant increase in the proportion of pre-surgical
      evaluations and surgery performed in non-teaching hospitals. CONCLUSIONS: Despite
      the increase in VEEG monitoring, the availability of guideline and evidences
      demonstrating benefits of epilepsy surgery was not associated with a greater
      employment of surgery over time. Nevertheless, access to pre-surgical evaluations
      and epilepsy surgery is no longer limited to large medical centers.

PMID- 22858309
TI  - Racial and socioeconomic disparities in epilepsy in the District of Columbia.
AB  - We investigated social and demographic factors as they relate to prevalence and
      incidence of epilepsy in Washington, DC, a culturally diverse area. Probability
      based sampling was used to select 20,000 households to complete a mailed epilepsy
      screening survey on all household members. Screened individuals with a history of
      epilepsy were sent a detailed case survey about seizures and treatment.
      Prevalence and incidence of epilepsy were estimated using weighted data. Lifetime
      prevalence was 1.53% overall; 0.77% in Whites, 2.13% in Blacks, and 3.4% in those
      with less than a high school diploma. Prevalence of active epilepsy was 0.79% and
      followed similar subgroup comparisons as lifetime prevalence. Age-adjusted
      lifetime and active epilepsy from multivariate analyses demonstrated
      significantly higher rates for Blacks compared to Whites and for those not
      completing high school compared to those that attended graduate school. The
      incidence of epilepsy was 71 per 100,000 persons. Adults with active epilepsy
      were significantly less likely to live alone than those without epilepsy.
      Residents of DC for <4 years had the lowest prevalence and incidence of all
      subgroups indicating a possible healthy mover effect. This is the first study to
      provide estimates and profiles of the epilepsy population in DC which can help
      better target resources to improve the health and outcomes of people with
      epilepsy and their families.

PMID- 22858310
TI  - Quantification of endostar in rat plasma by LC-MS/MS and its application in a
      pharmacokinetic study.
AB  - LC-MS/MS is a promising analytical platform for the quantification of recombinant
      therapeutic proteins in biological fluids for pharmacokinetic (PK) studies.
      Herein, an absolute quantification method based on LC-MS/MS technique was
      developed to quantify endostar, which is modified from the recombinant human
      endostatin by adding a nine-amino acid sequence (MGGSHHHHH) at the N-terminal. A
      reproducible three-step analytical procedure was adopted: (1) Ni(2+) Sepharose
      was used to selectively extract endostar; (2) the signature peptide
      "TEAPSATGQASSLLGGR" (m/z 802.3(2+)-651.8(2+)) of endostar and a synthetic peptide
      "TEAPSATGQVSSLLGGR" (m/z 816.9(2+)-666.4(2+)) as internal standard (IS) were
      selected and analyzed in the multiple reaction monitoring (MRM) mode; (3) the
      proposed method was validated and applied to the pharmacokinetic study of
      endostar. The lower limit of quantification (LLOQ) for quantifying endostar was
      50 ng/ml and this method is linear over 50-10,000 ng/ml. The accuracy was between
      85% and 115%, and the intra-batch and inter-batch analytic precision and accuracy
      were below 15%. This LC-MS/MS approach was validated for the application to the
      pharmacokinetic study of endostar in rats.

PMID- 22858311
TI  - Alcohol education revisited: exploring how much time we devote to alcohol
      education in the nursing curriculum.
AB  - INTRODUCTION: This study examines student nurses knowledge, attitudes and
      educational preparation to work with patients who misuse alcohol. The study
      begins to quantify how much time is devoted to alcohol education at one Scottish
      University. METHOD: The study modified the Short Alcohol Attitudes Problem
      Perception Questionnaire (SAAPPQ) and incorporated three case vignettes to
      examine the student nurses knowledge, attitudes and experience of working with
      patients who have an alcohol problem. The questionnaire was hand delivered to a
      convenience sample of third year nursing students. RESULTS: The results show that
      the student nurses exhibit positive attitudes and beliefs about working with
      patients who have an alcohol misuse problem. A series of significant associations
      was found between the adult nursing cohort and their ability to include a
      comprehensive alcohol history in their nursing assessments (chi(2) = 19.82, df =
      4, p < 0.0005); recognise signs of acute alcohol withdrawal (chi(2) = 52.26, df =
      16, p < 0.000); and the psychological signs associated with alcohol misuse
      (chi(2) = 41.81, df = 16, p < 0.000). A baseline figure of 2.5 h of alcohol
      education is noted at this university. CONCLUSIONS: Alcohol education strongly
      features in three out of the five nursing programmes surveyed. Nurse education
      needs to focus on strategies that extend to teaching nurses how to respond,
      provide brief interventions and identify when to refer the patient for specialist
      intervention. These approaches should be universal to all areas of nursing
      practice.

PMID- 22858312
TI  - Association of manganese superoxide dismutase and glutathione S-transferases
      genotypes with myocardial infarction in patients with type 2 diabetes mellitus.
AB  - AIM: In the present study we investigated the association between genetic
      polymorphisms with functional effects on redox regulation: Val16Ala of manganese
      superoxide dismutase (MnSOD), polymorphic deletions of glutathione S-transferases
      M1 (GSTM1) and T1 (GSTT1) and Ile105Val of glutathione S-transferase P1 (GSTP1)
      and myocardial infarction (MI) in a group of patients with type 2 diabetes
      mellitus. METHODS: The study population consisted of 463 Caucasian subjects with
      type 2 diabetes mellitus of more than 10 years' duration: 206 patients with MI
      and 257 patients with no history of coronary artery disease (CAD). Genotypes were
      determined by polymerase chain reaction (PCR) with restriction fragment length
      polymorphism (RFLP) and with multiplex PCR. RESULTS: The genotype distributions
      of tested single nucleotide polymorphisms did not show significant difference
      between cases and controls. After adjustment for age, gender, smoking, BMI,
      duration of diabetes and lipid parameters carriers of GSTM1/GSTT1-null haplotype
      showed an increased risk for MI (OR=3.22, 95% CI 1.37-5.04, p=0.03). CONCLUSIONS:
      The GSTM1/GSTT1 haplotype might be a genetic risk factor for MI in patients with
      type 2 diabetes mellitus.

PMID- 22858313
TI  - Outcomes following chemoradiotherapy for N3 head and neck squamous cell carcinoma
      without a planned neck dissection.
AB  - OBJECTIVES: The optimal management of the N3 neck in head and neck squamous cell
      carcinoma (HNSCC) remains controversial. We report the outcomes of patients with
      N3 disease treated with a strategy of concurrent chemo-radiotherapy (CRT)+/
      induction chemotherapy (ICT) without a planned neck dissection. MATERIALS AND
      METHODS: Forty patients with HNSCC N3 disease treated between January 2004 and
      December 2010 were retrospectively identified. Inclusion criteria for the study
      were: non-nasopharyngeal HNSCC, N3 nodal disease, intention to treat with CRT+/
      ICT. RESULTS: Median age was 60 (range 39-74). Median follow up was 32 months
      (range 8-88). 34 (85%) of patients received ICT. 35 patients received cisplatin
      CRT, 4 carboplatin-CRT and 1 patient was treated with radiotherapy alone due to
      ICT toxicity. 27 (67.5%) patients had a complete response (CR) to CRT. 5 (12.5%)
      patients had an incomplete response in both the primary and nodal sites. 8 (20%)
      patients had a CR in the primary site but incomplete in the nodal regions. The
      crude rate of regional failure following a CR was 3/27 (11.2%). Isolated regional
      failure occurred in 1/27 (3.7%) patients who had achieved a CR post-CRT. 3 year
      overall survival, disease free survival, locoregional control, local control and
      regional control in the whole cohort were 51.4%, 49.6%, 65.7%, 77.3%, 69.3%, and
      in patients with a CR were 73.3%, 70.0%, 86.6%, 90.5% and 91.7% respectively.
      CONCLUSION: Isolated regional nodal failure is rare following a complete response
      to CRT for N3 HNSCC managed without a planned neck dissection.

PMID- 22858314
TI  - Venous thromboembolism and its prophylaxis in elective knee arthroplasty: an
      international perspective.
AB  - INTRODUCTION: Patients undergoing knee arthroplasty are at high risk of
      developing post-operative deep vein thrombosis (DVT) or a pulmonary embolus (PE).
      Despite best efforts, the best prophylaxis for thromboembolic disease remains
      controversial. This article aims to update the reader on the newest guidelines
      concerning venous thromboembolism (VTE) prophylaxis for elective knee
      arthroplasty, highlighting their inconsistencies and why variations in
      recommendations exist. METHODS: The Medline database and the Internet were
      searched for VTE prophylaxis guidelines in English. 12 guidelines were found and
      compared. The comparison looked at the recommendations made, the grade of
      recommendation, the level of evidence available for these recommendations and any
      inconsistencies between the guidelines. RESULTS: Nearly all the guidelines
      advocate the use of low molecular weight heparin (LMWH) and Fondaparinux. There
      is little consensus in terms of other recommended drugs, the doses, duration and
      their recommendation grades. There are marked differences in the methodologies
      adopted by the different guideline working-groups. CONCLUSION: There is still
      uncertainty about the optimal methods of thromboprophylaxis in elective knee
      arthroplasty. Although there are always going to be disagreements about the
      endpoints amongst guideline makers, guidelines should achieve uniformity in their
      reporting of end-points, criteria for levels of evidence and recommendation
      grades, facilitating the clinician's decision-making process.

PMID- 22858315
TI  - Insights into fluorometabolite biosynthesis in Streptomyces cattleya DSM46488
      through genome sequence and knockout mutants.
AB  - Streptomyces cattleya DSM 46488 is unusual in its ability to biosynthesise
      fluorine containing natural products, where it can produce fluoroacetate and 4
      fluorothreonine. The individual enzymes involved in fluorometabolite biosynthesis
      have already been demonstrated in in vitro investigations. Candidate genes for
      the individual biosynthetic steps were located from recent genome sequences. In
      vivo inactivation of individual genes including those encoding the S-adenosyl-l
      methionine:fluoride adenosyltransferase (fluorinase, SCATT_41540), 5'-fluoro-5'
      deoxyadenosine phosphorylase (SCATT_41550), fluoroacetyl-CoA thioesterase
      (SCATT_41470), 5-fluoro-5-deoxyribose-1-phosphate isomerase (SCATT_20080) and a 4
      fluorothreonine acetaldehyde transaldolase (SCATT_p11780) confirm that they are
      essential for fluorometabolite production. Notably gene disruption of the
      transaldolase (SCATT_p11780) resulted in a mutant which could produce
      fluoroacetate but was blocked in its ability to biosynthesise 4-fluorothreonine,
      revealing a branchpoint role for the PLP-transaldolase.

PMID- 22858316
TI  - Thumb motor performance varies with thumb and wrist posture during single-handed
      mobile phone use.
AB  - Design features of mobile computing technology such as device size and key
      location may affect thumb motor performance during single-handed use. Since
      single-handed use requires the thumb posture to vary with key location, we
      hypothesize that motor performance is associated with thumb and wrist joint
      postures. A repeated measures laboratory experiment of 10 right-handed
      participants measured thumb and wrist joint postures during reciprocal tapping
      tasks between two keys for different key pairs among 12 emulated keys. Fitts'
      effective index of performance and joint postures at contact with each key were
      averaged across trials for each key. Thumb motor performance varied for different
      keys, with poorest performances being associated with excessive thumb flexion
      such as when tapping on keys closest to the base of the thumb in the bottom right
      corner of the phone. Motor performance was greatest when the thumb was in a
      typical resting posture, neither significantly flexed nor fully extended with
      slight CMC joint abduction and supination, such as when tapping on keys located
      in the top right and middle left areas on the phone. Grip was also significantly
      affected by key location, with the most extreme differences being between the top
      left and bottom right corners of the phone. These results suggest that keypad
      designs aimed at promoting performance for single-handed use should avoid placing
      frequently used functions and keys close to the base of the thumb and instead
      should consider key locations that require a thumb posture away from its limits
      in flexion/extension, as these postures promote motor performance.

PMID- 22858317
TI  - Overextended sarcomeres regain filament overlap following stretch.
AB  - Sarcomere overextension has been widely implicated in stretch-induced muscle
      injury. Yet, sarcomere overextensions are typically inferred based on indirect
      evidence obtained in muscle and fibre preparations, where individual sarcomeres
      cannot be observed during dynamic contractions. Therefore, it remains unclear
      whether sarcomere overextensions are permanent following injury-inducing stretch
      shortening cycles, and thus, if they can explain stretch-induced force loss. We
      tested the hypothesis that overextended sarcomeres can regain filament overlap in
      isolated myofibrils from rabbit psoas muscles. Maximally activated myofibrils
      (n=13) were stretched from an average sarcomere length of 2.6+/-0.04MUm by 0.9MUm
      sarcomere(-1) at a speed of 0.1MUm sarcomere(-1)s(-1) and immediately returned to
      the starting lengths at the same speed (sarcomere strain=34.1+/-2.3%). Myofibrils
      were then allowed to contract isometrically at the starting lengths (2.6MUm) for
      ~30s before relaxing. Force and individual sarcomere lengths were measured
      continuously. Out of the 182 sarcomeres, 35 sarcomeres were overextended at the
      peak of stretch, out of which 26 regained filament overlap in the shortening
      phase while 9 (~5%) remained overextended. About 35% of the sarcomeres with
      initial lengths on the descending limb of the force-length relationship and ~2%
      of the sarcomeres with shorter initial lengths were overextended. These findings
      provide first ever direct evidence that overextended sarcomeres can regain
      filament overlap in the shortening phase following stretch, and that the
      likelihood of overextension is higher for sarcomeres residing initially on the
      descending limb.

PMID- 22858318
TI  - Can micro-imaging based analysis methods quantify structural integrity of rat
      vertebrae with and without metastatic involvement?
AB  - This study compares the ability of MUCT image-based registration, 2D structural
      rigidity analyses and multimodal continuum-level finite element (FE) modeling in
      evaluating the mechanical stability of healthy, osteolytic, and mixed
      osteolytic/osteoblastic metastatically involved rat vertebrae. MUMR and MUCT
      images (loaded and unloaded) were acquired of lumbar spinal motion segments from
      15rnu/rnu rats (five per group). Strains were calculated based on image
      registration of the loaded and unloaded MUCT images and via analysis of FE models
      created from the MUCT and MUMR data. Predicted yield load was also calculated
      through 2D structural rigidity analysis of the axial unloaded MUCT slices.
      Measures from the three techniques were compared to experimental yield loads. The
      ability of these methods to predict experimental yield loads were evaluated and
      image registration and FE calculated strains were directly compared.
      Quantitatively for all samples, only limited weak correlations were found between
      the image-based measures and experimental yield load. In comparison to the
      experimental yield load, we observed a trend toward a weak negative correlation
      with median strain calculated using the image-based strain measurement algorithm
      (r=-0.405, p=0.067), weak significant correlations (p<0.05) with FE based median
      and 10th percentile strain values (r=-0.454, -0.637, respectively), and a trend
      toward a weak significant correlation with FE based mean strain (r=-0.366,
      p=0.09). Individual group analyses, however, yielded more and stronger
      correlations with experimental results. Considering the image-based strain
      measurement algorithm we observed moderate significant correlations with
      experimental yield load (p<0.05) in the osteolytic group for mean and median
      strain values (r=-0.840, -0.832, respectively), and in the healthy group for
      median strain values (r=-0.809). Considering the rigidity-based predicted yield
      load, we observed a strong significant correlation with the experimental yield
      load in the mixed osteolytic/osteoblastic group (r=0.946) and trend toward a
      moderate correlation with the experimental yield load in the osteolytic group
      (r=0.788). Qualitatively, strain patterns in the vertebral bodies generated using
      image registration and FEA were well matched, yet quantitatively a significant
      correlation was found only between mean strains in the healthy group (r=0.934).
      Large structural differences in metastatic vertebrae and the complexity of motion
      segment loading may have led to varied modes of failure. Improvements in load
      characterization, material properties assignments and resolution are necessary to
      yield a more generalized ability for image-based registration, structural
      rigidity and FE methods to accurately represent stability in healthy and
      pathologic scenarios.

PMID- 22858319
TI  - You might miss something obvious.

PMID- 22858321
TI  - Question about relapse of corrected deepbites.

PMID- 22858322
TI  - When less might be more.

PMID- 22858324
TI  - Treatment and stability of class II division 2 malocclusion in children and
      adolescents: a systematic review.
AB  - INTRODUCTION: Our objectives were to evaluate the evidence with regard to the
      effectiveness and stability of orthodontic treatment interventions for Class II
      Division 2 malocclusion in children and adolescents. This is a systematic review
      conducted according to the PRISMA statement. METHODS: The Cochrane Oral Health
      Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, and
      EMBASE were searched to November 2011. Relevant conference abstracts were also
      screened. No language restrictions were applied. Inclusion criteria were clinical
      studies with at least 20 subjects with Class II Division 2 malocclusion in which
      comparisons were made with an untreated Class II Division 2 malocclusion group,
      another treated Class II Division 2 malocclusion group, or neither. For included
      studies ranked best on the hierarchy of evidence, assessments of methodologic
      quality and risk of bias were undertaken. Abstracts and, when appropriate, full
      articles were examined independently by 2 investigators. Disagreements were
      resolved through discussion. Treatment changes and stability with or without
      retainers were measured with the following: skeletal, soft tissue, dental, and
      occlusal changes; gingival health; temporomandibular joint status and related
      muscular activity; and quality of life. RESULTS: Of the 322 studies identified in
      the search, 20 met the final inclusion criteria. All had a high risk of bias.
      CONCLUSIONS: Highly biased evidence exists with regard to management and
      stability of Class II Division 2 malocclusion. Guidelines are proposed based on
      current evidence.

PMID- 22858325
TI  - Cortical bone and ridge thickness of hyperdivergent and hypodivergent adults.
AB  - INTRODUCTION: The purpose of this study was to assess differences in dentoalvolar
      cortical bone thickness between hyperdivergent and hypodivergent young adults.
      METHODS: Pretreatment cone-beam computed tomography images of 57 patients,
      including 30 hypodivergent subjects (22 women, 8 men) and 27 hyperdivergent
      subjects (20 women, 7 men), were analyzed. The data were imported into imaging
      software (version 10.5; Dolphin Imaging Systems, Chatsworth, Calif); standardized
      orientations were used to measure buccal and lingual cortical bone thicknesses at
      16 interradicular sites of the maxilla and the mandible. Total alveolar ridge
      thickness and medullary space thickness were measured at the same sites. RESULTS:
      T tests showed significant (P <0.05) group differences, with hypodivergent
      subjects having significantly thicker buccal cortices. The lingual cortex of the
      maxilla was also significantly thicker in the hypodivergent than in the
      hyperdivergent subjects. Alveolar ridge thickness was significantly greater at
      all sites of the hypodivergent mandible and at the anterior 2 sites of the
      hypodivergent maxilla. Medullary thickness was significantly greater only in the
      hypodivergent mandibles between the first molars and the second premolars, and
      between the first and second premolars. Buccal cortical bone was significantly
      thicker than lingual cortical bone in the mandible; lingual bone was
      significantly thicker in the maxilla. CONCLUSIONS: Cortical bone tends to be
      thicker in hypodivergent than in hyperdivergent subjects. This explains the
      concomitant differences in alveolar ridge thickness. Medullary space thickness is
      largely unaffected by facial divergence.

PMID- 22858326
TI  - Mandibular dimensions of subjects with asymmetric skeletal class III malocclusion
      and normal occlusion compared with cone-beam computed tomography.
AB  - INTRODUCTION: The purpose of this study was to use cone-beam computed tomography
      to compare mandibular dimensions in subjects with asymmetric skeletal Class III
      malocclusion and those with normal occlusion. METHODS: Cone-beam computed
      tomography scans of 38 subjects with normal occlusion and 28 patients with facial
      asymmetry were evaluated and digitized with Invivo software (Anatomage, San Jose,
      Calif). Three midsagittal and 13 right and left measurements were taken. The
      paired t test was used to compare the right and left sides in each group. The
      Mann-Whitney U test was used to compare the midsagittal variables and the
      differences between the 2 sides of the group with normal occlusion with those of
      asymmetry patients. RESULTS: The posterior part of the mandibular body showed
      significant differences between the deviated and nondeviated sides in asymmetric
      Class III patients. The difference of the asymmetry group was significantly
      greater than that of the normal occlusion group for the mediolateral ramal and
      the anteroposterior condylar inclinations (P = 0.007 and P = 0.019,
      respectively). CONCLUSIONS: The asymmetric skeletal Class III group showed
      significant differences in condylar height, ramus height, and posterior part of
      the mandibular body compared with the subjects with normal occlusion. These
      results might be useful for diagnosis and treatment planning of asymmetric Class
      III patients.

PMID- 22858327
TI  - Effects of thread shape on the pullout strength of miniscrews.
AB  - INTRODUCTION: The aim of this study was to determine the effects of variations in
      thread shape on the axial pullout strength of orthodontic miniscrews. METHODS: A
      total of 35 miniscrews, 7 of each design being considered, were tested by
      performing pullout tests on a synthetic bone support. We used self-tapping and
      self-drilling miniscrews having a diameter of 2 mm and a thread shaft length of
      12 mm (the longest and the largest supplied by the manufacturer). A buttress
      reverse thread shape served as the control design and was tested against 4
      experimental designs, each manufactured with a modification in thread shape while
      maintaining all other characteristics. The experimental groups had the following
      thread designs: buttress, 75 degrees  joint profile, rounded, and trapezoidal.
      RESULTS: The control group with a buttress reverse thread shape had consistently
      higher pullout strength values than did the other designs. A statistically
      significant reduction in pullout force was found between the buttress reverse and
      the buttress thread miniscrews. CONCLUSIONS: Thread design influenced the
      resistance to pullout of the orthodontic miniscrews. The buttress reverse thread
      shape provided the greatest pullout strength.

PMID- 22858328
TI  - Clinical color intensity of white spot lesions might be a better predictor of
      enamel demineralization depth than traditional clinical grading.
AB  - INTRODUCTION: The aims of this study were to calculate the volume of white spot
      lesions by using microcomputed tomography and to determine which clinical
      attribute of the white spot lesion could better predict its volume: the
      clinically visible white spot lesion surface area or its color intensity.
      METHODS: White spot lesions were induced in 8 patients in vivo on 23 healthy
      premolars destined for extraction during orthodontic treatment by using specially
      designed plaque-retaining orthodontic bands. After 7 weeks, the premolars were
      extracted. After extraction, the resulting white spot lesions were photographed
      and clinically graded. The teeth were analyzed with microcomputed tomography.
      RESULTS: After 7 weeks, 70% of the teeth developed clinical white spot lesions.
      Clinically, the size of the lesions varied from minor to severe. Their volumes
      varied from 0 to 1.2931 mm(3). The traditional grades for white spot lesions
      correlated significantly with color intensity. A significant correlation was
      found between white spot lesion color intensity and lesion volume. This
      correlation was found to be better than that between the white spot lesion
      clinical score and lesion volume. CONCLUSIONS: Our results indicate that white
      spot lesion color intensity might predict the depth of enamel demineralization as
      well as or better than traditional white spot lesion scoring. Therefore, the
      dentist could use this information when planning treatment for white spot
      lesions.

PMID- 22858329
TI  - Accelerated decompensation of mandibular incisors in surgical skeletal class III
      patients by using augmented corticotomy: a preliminary study.
AB  - INTRODUCTION: Our objectives were to evaluate the amount of decompensation of the
      mandibular incisors and the change of periodontal support around them after
      corticotomy with bone augmentation before orthognathic surgery. METHODS: Before
      orthognathic surgery for 15 skeletal Class III patients, orthodontic treatment
      was combined with corticotomy and bone augmentation labially to the anterior
      mandibular roots. Lateral cephalograms were taken before orthodontic treatment
      and before surgery (completion of preoperative orthodontic treatment). The
      amounts of mandibular incisor proclination, alveolar bone thickness, and
      periodontal support (gingival margin levels and augmentation pattern) were
      evaluated. RESULTS: Significant proclination of the mandibular incisors was shown
      after decompensation (P <0.001; incisor mandibular plane angle, 10.45 degrees ;
      incisor symphyseal plane angle, 10.74 degrees ). The incisor edge moved labially
      by 3.47 mm. The alveolar bone thickness increased by 1.56 mm at the root apex and
      1.98 mm at the level of B-point (P <0.001). There was no gingival recession
      irrespective of the degree of proclination of the mandibular incisiors. Two types
      of bone augmentation pattern were evident. One was characterized by alveolar bone
      proclination proportional to the labial tipping of the mandibular incisors.
      Buccal alveolar bone at the cervical area was well maintained (60%, 9 subjects).
      The other showed greater increases in alveolar thickness at B-point than at the
      cervical area (40%, 6 subjects). CONCLUSIONS: The augmented corticotomy provided
      effective decompensation of the mandibular incisors in skeletal Class III
      patients while maintaining labial bone thickness and with no periodontal side
      effects. This technique reduces or eliminates the risk of moving the roots
      through the labial plate during decompensation with the associated risk of
      gingival recession.

PMID- 22858330
TI  - Palatal bone thickness compared with cone-beam computed tomography in adolescents
      and adults for mini-implant placement.
AB  - INTRODUCTION: The purpose of this study was to compare the bone thickness of the
      palatal areas in early and late mixed and early permanent dentitions according to
      dental age. METHODS: Cone-beam computed tomography scans of 118 subjects were
      selected and divided into 38 early mixed (8.03 +/- 0.93 years), 40 late mixed
      (11.51 +/- 0.92 years), and 40 permanent (20.92 +/- 1.17 years) dentition
      subjects. The measurements of palatal bone thickness were made at 49 sites by
      using InVivoDental5.0 software (Anatomage, San Jose, Calif). Repeated measures
      analysis of variance was used to analyze intragroup and intergroup differences as
      well as sex dimorphism. RESULTS: There was significantly lower bone thickness in
      the early mixed dentition group than in the 2 other groups (P <0.001). Bone
      thickness was higher in the anterior region than in the middle and posterior
      regions (P <0.001). Also, significant differences were found among the midline,
      medial, and lateral areas of the palate. CONCLUSIONS: Palatal bone thicknesses
      were significantly lower in the early mixed dentition group than in both the late
      mixed and permanent dentition groups. These findings might be helpful for
      clinicians to enhance the successful use of temporary anchorage devices in the
      palate.

PMID- 22858331
TI  - Motivation for orthodontic treatment investigated with Q-methodology: patients'
      and parents' perspectives.
AB  - INTRODUCTION: Motivation and cooperation are vital components of orthodontic
      treatment if a good outcome is to be achieved. In this study, we used Q
      methodology to investigate motivating factors among adolescents seeking
      orthodontic treatment and parents wanting their children to undergo orthodontic
      treatment. This technique asks participants to rank a series of statements, and
      the analysis of this ranking then provides insight into the participants'
      opinions. METHODS: Each of these complementary studies was divided into 2 phases:
      interviews to generate a list of reasons for seeking orthodontic treatment and
      the use of Q-methodology to assess and categorize the relative importance of
      these reasons for the groups of participants. In the patient study, 32 items were
      generated from the interviews and placed in order of importance on a Q
      methodology grid by 60 patients who were about to commence orthodontic treatment.
      The rankings were subjected to factor analysis, which categorized the patients'
      views into groups of shared opinions. The same methodology was used with the
      parent group, and a Q-methodology grid was designed to accommodate 35 items that
      were then ranked by the 60 parents. The rankings were subjected to factor
      analysis as for the patient group. RESULTS: For the patients, factor analysis
      identified 3 factors, all of which included esthetics, as important. The
      remaining respondents had more individual viewpoints and did not map to any of
      the 3 factors. For the parents, factor analysis identified 4 factors, all of
      which included treatment in adolescence to prevent future problems, as important.
      CONCLUSIONS: This study showed that Q-methodology is a novel and efficient tool
      that can be used in dental research with few difficulties. It might prove useful
      for the aspects of care for which subjective views or opinions play an important
      role.

PMID- 22858332
TI  - Relapse revisited--again.
AB  - INTRODUCTION: Long-term changes in the dentitions of orthodontic patients have
      been studied. However, most studies in the literature report findings after only
      a few years posttreatment. In this study, we examined records an average of 24
      years after active treatment. The purpose was to answer 2 questions: (1) does
      irregularity increase with time after treatment, and (2) how much relapse can be
      expected if a conservatively treated sample is recalled 2.5 decades after active
      treatment? METHODS: The sample consisted of dental casts of 52 women who were
      treated in the mid-1970s to the early 1980s with 0.022 * 0.028-in standard
      edgewise appliances. Each was given a maxillary Hawley retainer and either a
      mandibular Hawley or a banded canine-to-canine retainer at debanding. Retention
      lasted 24 to 32 months. The same practitioner treated all the patients. The
      sample is one of convenience; specifically, inclusion depended only on each
      patient's willingness to return for a recall examination. Records were collected
      at 3 examinations for each patient: start of treatment, end of the active phase
      of treatment, and long-term retention recall. The long-term maxillary and
      mandibular casts were measured and occluded in maximum intercuspation. Variables
      were measured, including incisor overjet and overbite, buccal segment
      relationship of the first molars and canines, and incisor irregularity in each
      arch. Variables were measured on the casts with digital readout sliding calipers
      precise to 0.001 mm. RESULTS: Mandibular incisor irregularity at recall was less
      than 3.5 mm in 77% of the patients examined. Correction of the maxillary incisor
      irregularity remained relatively stable over the time interval studied. Buccal
      segment Class II correction remained stable at the recall examination.
      CONCLUSIONS: Orthodontic treatment can yield reasonably good long-term stability
      in both occlusal correction and tooth alignment.

PMID- 22858333
TI  - Miniscrew design and bone characteristics: an experimental study of primary
      stability.
AB  - INTRODUCTION: The purpose of this study was to evaluate the correlations between
      bone characteristics, orthodontic miniscrew designs, and primary stability.
      METHODS: Four different miniscrews were placed in pig ribs. The miniscrews were
      first scanned with a scanning electron microscope to obtain measurable images of
      their threads. Subsequently, the maximum insertion torque of the screws and the
      maximum load value in the pullout force tests were measured; furthermore, bone
      specimen characteristics were analyzed by using cone-beam computed tomography.
      For each bone sample, the insertion site cortical thickness as well as both
      cortical and marrow bone density were evaluated. The nonparametric Kendall rank
      correlation (tau) was used to evaluate the strength of the associations among the
      characteristics measured. The nonparametric Kruskall-Wallis test was used to
      evaluate the differences among the groups, and post-hoc comparisons were assessed
      by using the Nemenyi-Damico-Wolfe-Dunn test. RESULTS: A significant dependence
      was found between pitch and maximum insertion torque (tau, -0.49). Positive
      correlations were also found between pullout force and maximum insertion torque
      (tau, 0.64), cortical thickness (tau, 0.36), and marrow bone density (tau, 0.35).
      CONCLUSIONS: In this in-vitro experimental study, strong correlations were
      observed among miniscrew geometry, bone characteristics, and primary stability.

PMID- 22858334
TI  - Multidisciplinary management including periodontics, orthodontics, implants, and
      prosthetics for an adult.
AB  - This article describes the complex dental treatment of an adult patient with
      multiple missing teeth, mild chronic periodontitis, and a malocclusion with a
      cant of the occlusal plane. After periodontal treatment, titanium implants and a
      miniscrew were placed to correct the occlusal plane canting with orthodontic
      treatment. Prosthodontic treatment was completed by using osseointegrated
      implants to replace the missing teeth.

PMID- 22858335
TI  - Two-phase treatment of skeletal class II malocclusion with the combination of the
      twin-block appliance and high-pull headgear.
AB  - The patient was a boy with a Class II skeletal and dental relationship, a large
      overjet, an impinging overbite, and a steep mandibular plane angle. Treatment
      started with the Twin-block appliance combined with high-pull headgear to promote
      growth of the mandible, restrain the maxilla in the anteroposterior and vertical
      planes, and improve his profile. This was followed by extraction of the maxillary
      second premolars and the mandibular first premolars. Then fixed appliances were
      used to align and level the dentition. Pretreatment and posttreatment records are
      shown, and the treatment results are stable 2 years after debonding.

PMID- 22858336
TI  - Complications of misdiagnosis of maxillary canine ectopic eruption.
AB  - Ectopic eruption of maxillary canines can be associated with root resorption of
      adjacent teeth. This case report describes and discusses an interesting case of a
      15-year-old girl with a Class III malocclusion and an impacted maxillary canine.
      Because of the unfavorable position of the ectopic canine and the severe root
      resorption of the maxillary left central and lateral incisors, the treatment
      options included extraction of the maxillary permanent canines. The mandibular
      first premolars were extracted to compensate for the Class III malocclusion. A
      panoramic radiograph taken earlier in the mixed dentition already indicated a
      possible eruption disturbance of the maxillary left permanent canine. The
      importance of early diagnosis of maxillary canine ectopic eruption is highlighted
      in this case report. The early identification of radiographic signs of an ectopic
      pathway of eruption should be followed by deciduous canine extraction to prevent
      canine retention and maxillary incisor root resorption.

PMID- 22858337
TI  - Laryngeal impaction of an archwire segment after accidental ingestion during
      orthodontic adjustment.
AB  - Orthodontic archwires or fractured appliances that are accidentally swallowed can
      become lodged in the airway or gastrointestinal tract. Inadvertent ingestion or
      aspiration of an appliance or archwire piece during orthodontic appliance
      adjustment is a medical emergency with potentially serious complications,
      including possible death from asphyxiation. This article reports the accidental
      ingestion of a piece of orthodontic archwire that became impacted in the larynx;
      it was subsequently retrieved. Some potential complications are discussed, along
      with suggested precautions to prevent such mishaps when using fixed appliances.

PMID- 22858338
TI  - Accuracy and reproducibility of 3-dimensional digital model measurements.
AB  - INTRODUCTION: The purpose of this study was to evaluate the reliability of
      measurements made on 3-dimensional digital models obtained with a surface laser
      scanner (D-250; 3Shape, Copenhagen, Denmark). METHODS: Twenty orthodontic dental
      casts of permanent dentitions were selected. Three-dimensional images were
      obtained on this scanner and analyzed by using the Geomagic Studio 5 software
      (Raindrop Geomagic, Inc, Morrisville, NC). Measurements were made with a digital
      caliper directly on the dental casts and also digitally on the digital models.
      Fifteen anatomic dental points were identified, and a total of 11 linear
      measurements were taken from each cast, including arch length and width.
      Dependent t tests were used to evaluate intraexaminer reproducibility and
      measurement accuracy on the digital models. RESULTS: No statistically significant
      differences were found between the measurements made directly on the dental casts
      and on the digital models. CONCLUSIONS: Linear measurements on digital models are
      accurate and reproducible. Digital models obtained with the surface laser scanner
      are reliable for measurements of arch width and length.

PMID- 22858339
TI  - Litigation and legislation. I'm sorry, so sorry.

PMID- 22858340
TI  - Cluster-randomized controlled trials: part 1.

PMID- 22858341
TI  - Unilateral maxillary molar distalization with zygoma-gear appliance.
AB  - The aim of this study was to present the orthodontic treatment of a 15-year-old
      boy with a unilateral maxillary molar distalization system, called the zygoma
      gear appliance. It consisted of a zygomatic anchorage miniplate, an inner bow,
      and a Sentalloy closed coil spring (GAC International, Bohemia, NY). A
      distalizing force of 350 g was used during the distalization period. The
      unilateral Class II malocclusion was corrected in 5 months with the zygoma-gear
      appliance. The maxillary left first molar showed distalization of 4 mm with an
      inclination of 3 degrees . The maxillary premolars moved distally with the help
      of the transseptal fibers. In addition, there were slight decreases in overjet (
      0.5 mm) and maxillary incisor inclination (-1 degrees ), indicating no anchorage
      loss from the zygoma-gear appliance. Preadjusted fixed appliances (0.022 * 0.028
      in, MBT system; 3M Unitek, Monrovia, Calif) were placed in both arches to achieve
      leveling and alignment. After 14 months of unilateral distalization with the
      zygoma-gear appliance and fixed appliances, Class I molar and canine
      relationships were established with satisfactory interdigitation of the posterior
      teeth. Acceptable overjet and overbite were also achieved. This article shows
      that this new system, the zygoma-gear appliance, can be used for unilateral
      maxillary molar distalization without anchorage loss.

PMID- 22858343
TI  - Epidemiology of chronic pain: a population-based nationwide study on its
      prevalence, characteristics and associated disability in Portugal.
AB  - A cross-sectional nationwide epidemiological study was performed in a random
      sample of the Portuguese adult population, aiming to describe the prevalence and
      impact of chronic pain (CP). The 5,094 participants were selected by random digit
      dialing, between January 2007 and March 2008, and estimates were adequately
      weighted for the population. Prevalence of CP was 36.7% (95% confidence interval
      [CI] [35.3-38.2]), based on the definition of the International Association for
      the Study of Pain. Recurrent or continuous pain was present in 85% of those with
      CP, and moderate-to-severe intensity and disability were present in 68 and 35%,
      respectively. Highest CP prevalence was observed among the elderly, retired,
      unemployed, and less educated. Highest disability was found in relation with
      family/home responsibilities, recreational activities, occupation/work, and
      sleep/rest; 13% reported a diagnosis of depression and 49% reported interference
      in their job. The main factors associated with disability were sex, pain
      intensity, and depression or depressive symptoms. CP is highly prevalent, causes
      high personal and social burden, and affects particularly the most vulnerable
      subgroups. Portugal, depending on CP definition, could be placed in the lower
      prevalence group in Europe. Improvement in pain intensity management and special
      attention to affective components of CP are recommended. PERSPECTIVE: In this
      cross-sectional nationwide epidemiological study, we showed that chronic pain is
      a significant problem that is present in 37% of the Portuguese adult general
      population, is associated with high personal, family, and social burden, and
      affects in particular the most vulnerable subgroups of the population.

PMID- 22858342
TI  - Mechanisms of G protein-coupled estrogen receptor-mediated spinal nociception.
AB  - Human and animal studies suggest that estrogens are involved in the processing of
      nociceptive sensory information and analgesic responses in the central nervous
      system. Rapid pronociceptive estrogenic effects have been reported, some of which
      likely involve G protein-coupled estrogen receptor (GPER) activation. Membrane
      depolarization and increases in cytosolic calcium and reactive oxygen species
      (ROS) levels are markers of neuronal activation, underlying pain sensitization in
      the spinal cord. Using behavioral, electrophysiological, and fluorescent imaging
      studies, we evaluated GPER involvement in spinal nociceptive processing.
      Intrathecal challenging of mice with the GPER agonist G-1 results in pain-related
      behaviors. GPER antagonism with G15 reduces the G-1-induced response.
      Electrophysiological recordings from superficial dorsal horn neurons indicate
      neuronal membrane depolarization with G-1 application, which is G15 sensitive. In
      cultured spinal sensory neurons, G-1 increases intracellular calcium
      concentration and induces mitochondrial and cytosolic ROS accumulation. In the
      presence of G15, G-1 does not elicit the calcium and ROS responses, confirming
      specific GPER involvement in this process. Cytosolic calcium concentration
      elevates faster and with higher amplitude following G-1 intracellular
      microinjections compared to extracellular exposure, suggesting subcellular GPER
      functionality. Thus, GPER activation results in spinal nociception, and the
      downstream mechanisms involve cytosolic calcium increase, ROS accumulation, and
      neuronal membrane depolarization. PERSPECTIVE: Our results suggest that GPER
      modulates pain processing in spinal sensory neurons via cytosolic calcium
      increase and ROS accumulation. These findings extend the current knowledge on
      GPER involvement in physiology and disease, providing the first evidence of its
      pronociceptive effects at central levels and characterizing some of the
      underlying mechanisms.

PMID- 22858344
TI  - The expression of pain behaviors in high catastrophizers: the influence of
      automatic and controlled processes.
AB  - In the present study, patients with musculoskeletal pain conditions (n = 55) were
      filmed while performing a lifting task designed to elicit pain behaviors.
      Patients were asked to perform the lifting task twice, under 2 distinct
      conditions. In the first condition, patients were asked to rate their pain while
      lifting a series of weights. In the second condition, patients were asked to
      estimate the weight of the objects they lifted. The weight estimation condition
      was conceived as a way to increase the cognitive load associated with the lifting
      task. The primary purpose of the present study was to examine whether
      manipulation of cognitive load differentially influenced the expression of pain
      behaviors in high and low catastrophizers. During the pain rating condition,
      results indicated that high catastrophizers displayed significantly higher levels
      of communicative and protective pain behaviors than low catastrophizers. During
      the weight estimation condition, however, high and low catastrophizers no longer
      differed in the expression of communicative pain behaviors. These results suggest
      that increasing cognitive load during a pain-eliciting task may interfere with
      the expression of communicative pain behaviors in high catastrophizers. The
      discussion addresses the potential role of automatic and cognitive control
      processes in the expression of pain behaviors. PERSPECTIVE: The present study
      provides new insights into the processes that might underlie the expression of
      pain behaviors in patients with high levels of catastrophizing. Our findings
      could have implications for the management of patients presenting with pain
      conditions, particularly those with high levels of catastrophizing.

PMID- 22858345
TI  - Surgical treatment of enophthalmos using an endoscope and T-shaped porous
      polyethylene fabricated with a mirror image.
AB  - Enophthalmos is corrected mostly through reducing the enlarged orbit volume by
      identifying intact bone edges and spanning the defect with an implant or
      autogenous graft. Predicting the amount of volume which must be added to correct
      enophthalmos is not easy using this method, and the outcome may be
      unsatisfactory. In this study, the authors examined 9 patients in whom
      enophthalmos was caused by a defect or inadequate surgery of the orbital medial
      wall. The authors designed an adequately shaped implant by using the mirror image
      obtained before surgery, and prepared a T-shaped Medpor for each patient in order
      to maintain the accurate contour of the medial wall and to decrease the enlarged
      orbital volume. During the surgery, the T-shaped Medpor was inserted while
      monitoring the posterior portion of the orbital wall. Satisfactory results were
      obtained for all the patients. Although the new method of implant design
      developed by the authors in this study is limited to the reconstruction of the
      medial wall, it is considered useful for the surgical treatment of posttraumatic
      enophthalmos because it takes into account both the contour and volume of the
      orbital wall.

PMID- 22858346
TI  - Epidemiology of football injuries in Asia: a prospective study in Qatar.
AB  - OBJECTIVES: To investigate the incidence, characteristics and patterns of
      football injuries at club level in Qatar. DESIGN: Prospective cohort study.
      METHODS: Data were prospectively collected from the first division football
      league clubs in Qatar, in accordance with the international consensus statement
      on football injury epidemiology. An injury was defined as any physical complaint
      sustained during football activity resulting in the inability to participate
      fully in the next training or match. Individual injuries and exposure of each
      player were recorded by the medical staff of each team over one season. RESULTS:
      A total of 217 injuries were recorded, with an injury rate during matches of
      14.5/1000h (95% CI: 11.6-18.0) compared with 4.4/1000h during training sessions
      (95% CI: 3.7-5.2). More than one third of all injuries were muscle strains
      (36.4%). Hamstring strains (54.4% of all muscle strains) exhibited a higher
      incidence than all other injury types (p<0.001). The thigh was the most frequent
      injury location (41.9%, p<0.001). Reinjuries (15% of total injuries) were mainly
      comprised of muscle strains associated with a higher severity compared with new
      injuries. CONCLUSIONS: Despite the different environmental, social and cultural
      setting, our findings are comparable with previous data from European club
      football, confirming the previous finding at national team level that there are
      no regional peculiarities of football injuries in this part of the Asiatic
      continent. The relatively high overuse injury incidence rate and the high
      recurrence rate for (severe) thigh muscle strains, especially during games,
      warrants prevention strategies.

PMID- 22858348
TI  - Is dydrogesterone progesterone?

PMID- 22858349
TI  - The ultrastructural characteristics of the spermatozoa stored in the cauda
      epididymidis in Chinese soft-shelled turtle Pelodiscus sinensis during the
      breeding season.
AB  - The ultrastructure of spermatozoa in cauda epididymidis of soft-shelled turtle,
      P. sinensis during breeding season was investigated by light microscopy (LM) and
      electron microscopy (TEM and SEM). The mature spermatozoa appeared elongated and
      filiform. In general, the turtle spermatozoon contains a characteristic head,
      midpiece and tail, similar in morphology to that of birds, amphibians and other
      reptiles. However, several features are unique. These include (1) three
      intranuclear tubules containing dense core extend from the subacrosomal cone
      through the rostral nucleus and deep into the nuclear body; (2) the midpiece is
      composed of 40 mitochondria which present a staggered rings-and-columns
      arrangement (8 parallel rings and 5 columns); (3) unusual spherical mitochondria
      with a dense core are surrounded by 8-10 concentric layers of cristae.
      Surprisingly, about 21.4+/-3.6 percent immature spermatozoa with normal
      morphology are also observed in this season. Different from the mature
      spermatozoa, a variable amount of cytoplasm droplets are attached to the immature
      spermatozoa under SEM. Some spermatozoa still show the tail coiled tightly around
      the cytoplasm. These spermatozoa in transverse sections under TEM, showed a large
      amount of cytoplasm wrapped by plasma membrane; even some free mitochondria and
      higher electron density material still seen in the cytoplasm. Among the immature
      spermatozoa, most of them possess a cytoplasmic droplet which is located
      eccentrically on the midpiece, and contains a lot of lipid droplets in addition
      to hollow vesicles. Lipid droplets are closely associated with mitochondrial
      membranes and may function in the formation or degradation of mitochondria. These
      immature spermatozoa may be the dormant cells, but whether or not they can
      fertilize the ovum or not is unknown. Thus, in the present study we hypothesized
      that the cauda epididymidis might be involved in the sperm maturation in this
      species.

PMID- 22858351
TI  - The subscale structure of the Inventory of Depressive Symptomatology Self Report
      (IDS-SR) in older persons.
AB  - BACKGROUND: Using symptom dimensions may be more effective than using categorical
      subtypes when investigating clinical outcome and underlying mechanisms of late
      life depression. Therefore, this study aims to identify both the factor and
      subscale structure of late-life depression underlying the Inventory of Depressive
      Symptomatology Self Report (IDS-SR) in older persons. METHOD: IDS-SR data of 423
      participants in the Netherlands Study of Depression in Older Persons (NESDO) were
      analyzed by exploratory (EFA) and confirmatory factor analysis (CFA). The best
      fitting factor solution in a group of older persons with a major depressive
      disorder diagnosis in the last month (n = 229) was replicated in a control group
      of older persons with no or less severe depression (n = 194). Multiple group (MG
      CFA) was performed to evaluate generalizability of the best-fitting factor
      solution across subgroups, and internal consistency coefficients were calculated
      for each factor. RESULTS: EFA and CFA show that a 3-factor model fits best to the
      data [comparative fit index (CFI) = 0.98; Tucker Lewis Index (TLI) = 0.99; and
      root mean square error of approximation (RMSEA) = 0.052], consisting of a 'mood',
      'motivation' and 'somatic' factor with adequate internal consistencies (alpha
      coefficient 0.93, 0.83 and 0.70, respectively). MG-CFA shows a structurally
      similar factor model across subgroups. CONCLUSION: The IDS-SR can be used to
      measure three homogeneous symptom dimensions that are specific to older people.
      Application of these dimensions that may serve as subscales of the IDS-SR may
      benefit both clinical practice and scientific research.

PMID- 22858353
TI  - Diagnostic specificity of poor premorbid adjustment: comparison of schizophrenia,
      schizoaffective disorder, and mood disorder with psychotic features.
AB  - Individuals with schizophrenia have significant deficits in premorbid social and
      academic adjustment compared to individuals with non-psychotic diagnoses.
      However, it is unclear how severity and developmental trajectory of premorbid
      maladjustment compare across psychotic disorders. This study examined the
      association between premorbid functioning (in childhood, early adolescence, and
      late adolescence) and psychotic disorder diagnosis in a first-episode sample of
      105 individuals: schizophrenia (n=68), schizoaffective disorder (n=22), and mood
      disorder with psychotic features (n=15). Social and academic maladjustment was
      assessed using the Cannon-Spoor Premorbid Adjustment Scale. Worse social
      functioning in late adolescence was associated with higher odds of schizophrenia
      compared to odds of either schizoaffective disorder or mood disorder with
      psychotic features, independently of child and early adolescent maladjustment.
      Greater social dysfunction in childhood was associated with higher odds of
      schizoaffective disorder compared to odds of schizophrenia. Premorbid decline in
      academic adjustment was observed for all groups, but did not predict diagnosis at
      any stage of development. Results suggest that social functioning is disrupted in
      the premorbid phase of both schizophrenia and schizoaffective disorder, but
      remains fairly stable in mood disorders with psychotic features. Disparities in
      the onset and time course of social dysfunction suggest important developmental
      differences between schizophrenia and schizoaffective disorder.

PMID- 22858352
TI  - Testosterone levels in suicide attempters with bipolar disorder.
AB  - OBJECTIVE: The best known neurobehavioral effects of testosterone are on sexual
      function and aggression. However, testosterone and other androgens may be
      involved in the pathophysiology of mood disorders and suicidal behavior. This is
      the first study to examine whether there is a relation between testosterone
      levels and clinical parameters in bipolar suicide attempters. METHODS: Patients
      with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a
      depressive or mixed episode with at least one past suicide attempt were enrolled.
      Demographic and clinical parameters, including lifetime suicidal behavior, were
      assessed and recorded. Plasma testosterone was assayed using a double antibody
      radioimmunoassay procedure. RESULTS: The number of major depressive episodes, the
      maximum lethality of suicide attempts, and the testosterone levels were higher in
      men compared to women. Current suicidal ideation scores were higher in women
      compared to men. Controlling for sex, we found that testosterone levels
      positively correlated with the number of manic episodes and the number of suicide
      attempts. CONCLUSION: Our findings are consistent with previous observations of
      the association between testosterone levels and parameters of mood and behavior.
      This study suggests that testosterone levels may be related to the course of
      bipolar disorder and suicidal behavior. Further studies of the role of
      testosterone in the neurobiology of mood disorders and suicidal behavior are
      merited.

PMID- 22858354
TI  - Handling e-waste in developed and developing countries: initiatives, practices,
      and consequences.
AB  - Discarded electronic goods contain a range of toxic materials requiring special
      handling. Developed countries have conventions, directives, and laws to regulate
      their disposal, most based on extended producer responsibility. Manufacturers
      take back items collected by retailers and local governments for safe destruction
      or recovery of materials. Compliance, however, is difficult to assure, and
      frequently runs against economic incentives. The expense of proper disposal leads
      to the shipment of large amounts of e-waste to China, India, Pakistan, Nigeria,
      and other developing countries. Shipment is often through middlemen, and under
      tariff classifications that make quantities difficult to assess. There, despite
      the intents of national regulations and hazardous waste laws, most e-waste is
      treated as general refuse, or crudely processed, often by burning or acid baths,
      with recovery of only a few materials of value. As dioxins, furans, and heavy
      metals are released, harm to the environment, workers, and area residents is
      inevitable. The faster growth of e-waste generated in the developing than in the
      developed world presages continued expansion of a pervasive and inexpensive
      informal processing sector, efficient in its own way, but inherently hazard
      ridden. 

PMID- 22858355
TI  - Analysis of monitoring programmes and their suitability for ecotoxicological risk
      assessment in four Spanish basins.
AB  - Data from four Spanish basin management authorities were analysed. Chemical and
      biological data from four Spanish basin management authorities were analysed,
      focusing on three consecutive years. Aims were to i) determine the chemicals most
      likely responsible for the environmental toxicological risk in the four Spanish
      basins and ii) investigate the relationships between toxicological risk and
      biological status in these catchments. The toxicological risk of chemicals was
      evaluated using the toxic unit (TU) concept. With these data we considered if the
      potential risk properly reflects the risk to the community or, alternatively, if
      new criteria should be developed to improve risk assessment. Data study revealed
      inadequacies in processing and monitoring that should be improved (e.g., site
      coincidence for chemical and biological sampling). Analysis of the chemical data
      revealed high potential toxicological risk in the majority of sampling points, to
      which metals were the main contributors to this risk. However, clear
      relationships between biological quality and chemical risk were found only in one
      river. Further investigation of metal toxicity may be necessary, and future
      analyses are necessary to accurately estimate the risk to the environment.

PMID- 22858356
TI  - Could heart rate play a role in pericardial inflammation?
AB  - PURPOSE AND MEDICAL HYPOTHESIS: Rest is usually recommended in acute
      pericarditis, as it could help to lower heart rate (HR) and contribute to limit
      "mechanical inflammation". Whether HR on admission could be correlated and
      perhaps participate to inflammation has not been reported. METHODS: Between March
      2007 and February 2010, we conducted a retrospective study on all patients
      admitted to our center for acute pericarditis. Diagnosis criteria included two of
      the following ones: typical chest pain, friction rub, pericardial effusion on
      cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint
      was biology: CRP on admission, on days 1, 2, 3, and especially peak. RESULTS: We
      included 73 patients. Median age was 38 years (interquartiles 28-51) and median
      hospitalization duration was 2.0 days (1.5-3.0). Median heart rate was 88.0 beats
      per minute (bpm) on admission (interquartiles 76.0-100.0) and 72.0 on discharge
      (65.0-80.0). Heart rate on admission was significantly correlated with CRP peak
      (p<0.001), independently of temperature on admission, hospitalization duration
      and age. Recurrences occurred within 1 month in 32% of patients. Heart rate on
      hospital discharge was correlated with recurrence, independently of age.
      CONCLUSION: In acute pericarditis, heart rate on admission is independently
      correlated with CRP levels and heart rate on discharge seems to be independently
      correlated to recurrence. This could suggest a link between heart rate and
      pericardial inflammation.

PMID- 22858357
TI  - Bone QUS measurement performed under loading condition, a more accuracy
      ultrasound method for osteoporosis diagnosis.
AB  - Osteoporosis is a worldwide health problem with enormous social and economic
      impact. Quantitative ultrasound (QUS) method provides comprehensive information
      on bone mass, microstructure and mechanical properties of the bone. And the
      cheap, safe and portable ultrasound equipment is more suitable for public health
      monitoring. QUS measurement was normally performed on bone specimens without
      mechanical loading. But human bones are subjected to loading during routine daily
      activities, and physical loading leads to the changes of bone microstructure and
      mechanical properties. We hypothesized that bone QUS parameters measured under
      loading condition differ from those measured without loading because the
      microstructure of bone was changed when loading subjected to bone. Furthermore,
      when loading was subjected on bone, the loading-lead microstructure change of
      osteoporosis bone may larger than that of health bone. By considering the high
      relationship between bone microstructure and QUS parameters, the QUS parameters
      of osteoporosis bone may changed larger than that of health bone. So osteoporosis
      may be detected more effectively by the combination of QUS method and mechanical
      loading.

PMID- 22858358
TI  - Confirmation of the "protein-traffic-hypothesis" and the "protein-localization
      hypothesis" using the diabetes-mellitus-type-1-knock-in and transgenic-murine
      models and the trepitope sequences.
AB  - As possible mechanisms to explain the emergence of autoimmune diseases, the
      current author has suggested in earlier papers two new pathways: the "protein
      localization hypothesis" and the "protein traffic hypothesis". The "protein
      localization hypothesis" states that an autoimmune disease develops if a protein
      accumulates in a previously unoccupied compartment, that did not previously
      contain that protein. Similarly, the "protein traffic hypothesis" states that a
      sudden error within the transport of a certain protein leads to the emergence of
      an autoimmune disease. The current article discusses the usefulness of the
      different commercially available transgenic murine models of diabetes mellitus
      type 1 to confirm the aforementioned hypotheses. This discussion shows that
      several transgenic murine models of diabetes mellitus type 1 are in-line and
      confirm the aforementioned hypotheses. Furthermore, these hypotheses are
      additionally inline with the occurrence of several newly discovered protein
      sequences, the so-called trepitope sequences. These sequences modulate the immune
      response to certain proteins. The current study analyzed to what extent the
      hypotheses are supported by the occurrence of these new sequences. Thereby the
      occurrence of the trepitope sequences provides additional evidence supporting the
      aforementioned hypotheses. Both the "protein localization hypothesis" and the
      "protein traffic hypothesis" have the potential to lead to new causal therapy
      concepts. The "protein localization hypothesis" and the "protein traffic
      hypothesis" provide conceptional explanations for the diabetes mouse models as
      well as for the newly discovered trepitope sequences.

PMID- 22858359
TI  - Ustekinumab associated thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare disorder. Plasma exchange
      therapy has been shown to significantly reduce mortality in patients with TTP.
      Here, we report a case of TTP associated with ustekinumab therapy after a period
      of 2-3 years. Ustekinumab, a monoclonal antibody that inhibits interleukin 12 and
      interleukin 23, is one of the newer treatments for psoriasis. Although our
      patient experienced a prolonged course of TTP requiring 1 month of daily plasma
      exchange therapy, he recovered and remains in remission after 6 months.

PMID- 22858360
TI  - Fungal infections: the next challenge.

PMID- 22858361
TI  - Prototheca wickerhamii as a cause of neuroinfection in a child with congenital
      hydrocephalus. First case of human protothecosis in Poland.
AB  - This report describes a rare case of neuroinfection due to Prototheca wickerhamii
      in a child with severe, congenital hydrocephalus. The infection resolved
      completely after the patient was treated with oral ketoconazole, followed by
      intravenous fluconazole and amphotericin B. A probable source of infection was
      contamination during ventriculoperitoneal drain care procedures.

PMID- 22858362
TI  - ASCO 2012: a good year for HER2 therapy.

PMID- 22858363
TI  - Chiral drug analysis using mass spectrometric detection relevant to research and
      practice in clinical and forensic toxicology.
AB  - This paper reviews analytical approaches published in 2002-2012 for chiral drug
      analysis and their relevance in research and practice in the field of clinical
      and forensic toxicology. Separation systems such as gas chromatography, high
      performance liquid chromatography, capillary electromigration, and supercritical
      fluid chromatography, all coupled to mass spectrometry, are discussed. Typical
      applications are reviewed for relevant chiral analytes such as amphetamines and
      amphetamine-derived designer drugs, methadone, tramadol, psychotropic and other
      CNS acting drugs, anticoagulants, cardiovascular drugs, and some other drugs.
      Usefulness of chiral drug analysis in the interpretation of analytical results in
      clinical and forensic toxicology is discussed as well.

PMID- 22858364
TI  - Contribution of oxidized tallow to aroma characteristics of beeflike process
      flavour assessed by gas chromatography-mass spectrometry and partial least
      squares regression.
AB  - Flavour profiles of seven beeflike process flavours (BFs) including non-oxidized
      or oxidized tallow were comparatively analysed by electronic nose, gas
      chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis to
      characterize the headspace of BFs. Analysis of volatiles by GC-MS indicated that
      the effect of oxidized tallow with moderate oxidization level on Maillard
      reaction was more prominent than that of others, which potentially could result
      in an optimal meat flavour with strong, harmony and species-specific
      characteristics detected by sensory analysis. In addition, electronic nose data
      confirmed the accuracy of the GC-MS and sensory analysis results. Correlation
      analysis of the electronic nose measurements, sensory evaluation and
      characteristic compounds through Partial Least Squares Regression (PLSR) further
      explained that moderate oxidized tallow with peroxide value (PV) of 87.67-160
      mequiv./kg, the p-anisidine value (p-AV) of 30.57-50, and the acid value (AV) of
      1.8-2.2 mg KOH/g tallow was a desirable precursor for imparting aroma
      characteristics of beef flavour.

PMID- 22858365
TI  - The effects of polyphenols on oxidative stress and the arachidonic acid cascade.
      Implications for the prevention/treatment of high prevalence diseases.
AB  - Redox state unbalance and the activation of the arachidonic acid (AA) cascade,
      contribute to the pathogenesis of cardiovascular disease (CVD) and cancer.
      Inflammatory cells that infiltrate the atheroma plaque or tumor are a major
      source of reactive oxygen species and eicosanoids. The human antioxidant defense
      network is complex and interlocking and there is controversy surrounding the
      beneficial effects of diet-derived antioxidants in vivo. However, epidemiological
      studies indicate that populations that consume high levels of plant-derived foods
      containing phenolic compounds have low rates of CVD and cancer. The molecular
      mechanisms for these effects are multi-faceted. They include the regulation of
      transcription factors and consequently the modulation of genes (cytokines, growth
      factors and adhesion molecules), and growth factor-receptor interactions and cell
      signaling cascades, which determine the expression of genes involved in cell
      cycle, cell survival and apoptosis, as well as adhesiveness/invasiveness and
      angiogenesis. The present paper also focuses on the effects of phenolic compounds
      on AA cascade enzymes (cyclooxygenases and lipoxygenases) and the subsequent
      synthesis of eicosanoids, which are involved in CVD and cancer. A better
      understanding of these processes could explain the beneficial effects of
      polyphenols on the most prevalent diseases in Western societies. This commentary
      shows that antioxidants under evaluation include structural modifications of low
      molecular-mass polyphenols, which could lead to a valuable strategy for
      modulating the generation of inflammatory mediators involved in these chronic
      diseases.

PMID- 22858366
TI  - Successful management of cardiogenic shock with intracoronary nitroglycerin in a
      patient with left main coronary artery lesion.

PMID- 22858367
TI  - An uncommon complication of infective bacterial endocarditis.
AB  - Coronary artery septic embolisation resulting in cardioembolic myocardial
      infarction (MI) is a rare complication of bacterial infective endocarditis (IE),
      representing <1% of complications related to IE. Diagnosis requires a combination
      of high clinical suspicion, coronary angiography, echocardiography and cultures
      of peripheral blood and/or embolic material. The associated mortality rate
      remains high despite early diagnosis. Optimal interventional therapy is unknown
      with published international experience over the past two decades limited to very
      small case series and individual case reports. We present a case of ST elevation
      MI resulting from coronary artery septic embolisation with an accompanying
      comprehensive review of the literature.

PMID- 22858369
TI  - Effect of transfer delay on left ventricular function after primary PCI for ST
      elevation myocardial infarction.
AB  - BACKGROUND: Primary PCI (PPCI) is superior to thrombolysis for treatment of acute
      ST Elevation Myocardial Infarction (STEMI). However, transfer to a PCI centre
      results in a treatment delay compared to those presenting directly to such
      hospitals. The aim of this study was to investigate the influence of transfer
      delay on LV function and clinical outcomes in PPCI patients. METHODS: Of 113
      consecutive PPCI patients, 69 presented directly to the PCI centre and 44 were
      transferred. Echocardiography was performed at day 1 and after 6 weeks to assess
      LV function using the Wall Motion Score Index (WMSI). Patients were followed for
      a mean of 3.51 years. RESULTS: There was no significant difference in WMSI at day
      1 between local and transfer patients (1.52+/-0.36 and 1.48+/-0.34 respectively,
      p=ns). After 6 weeks the WMSI improved significantly in both groups (1.33+/-0.33
      and 1.31+/-0.31 respectively, p<0.001 for both). On multivariate analysis, pain
      to balloon time>160 min, LAD stenosis and initial TIMI flow 0-1 were significant
      independent predictors of LV dysfunction. There was no significant difference in
      clinical events during long term follow up. CONCLUSIONS: Patients transferred for
      PPCI had similar LV function and clinical outcomes compared to those who
      presented directly to a PCI hospital.

PMID- 22858370
TI  - Dioxin-like activity in environmental and human samples from Greenland and
      Denmark.
AB  - Dioxins and dioxin-like (DL) compounds are some of the most toxic chemicals being
      highly persistent in the environment. The toxicological effects of dioxins are
      mediated via the aryl hydrocarbon receptor (AhR). Compounds of diverse structure
      and lipophility can bind and activate AhR. The AhR transactivation bioassay is
      utilized in an array of projects to study the AhR-mediated activities of
      individual chemicals and mixtures and for epidemiological purposes. This review
      summarizes a series of studies regarding the DL-activity of single compounds and
      complex compound mixtures in the environment and humans. We found that some
      pesticides, plasticizers and phytoestrogens can activate the AhR, and the
      combined effect of compounds with no or weak AhR potency cannot be ignored. The
      significant DL-activity in the wastewater effluent indicates the treatment is not
      sufficient to prevent contamination of surface waters with dioxins. Our results
      from human studies suggest that the serum DL-activity reflect the complex mixture
      of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL
      activity level compared to Europeans, probably due to long distance from the
      dioxin sources and UV degradation of the high potent dioxin and/or the inhibitory
      effect of the high level of non-DL POPs. Selective bioaccumulation of PCBs in the
      food chain may contribute to the negative correlation between serum POPs and DL
      activity observed in Greenlandic Inuit. Hence the AhR transactivation bioassay
      provides a cost-effective and integrated screening tool for measurement of the DL
      activity in human, environmental and commercial samples.

PMID- 22858371
TI  - Cerebrospinal fluid anti-whole myelin antibodies are not correlated to magnetic
      resonance imaging activity in multiple sclerosis.
AB  - BACKGROUND: The role of antimyelin antibodies as biomarker in multiple sclerosis
      is subject of debate. Here antimyelin antibody reactivity against native myelin
      is studied in CSF and serum. OBJECTIVE: To compare antimyelin antibody reactivity
      between patients with multiple sclerosis (MS) and patients with other
      neurological diseases in CSF and serum. In addition, MRI measures were studied in
      relation to antimyelin antibody reactivity. METHODS: 77 MS patients (13 primary
      progressive, 27 secondary progressive and 37 relapsing remitting), 26 patients
      with other non-inflammatory neurological diseases and 9 patients with
      inflammatory neurological diseases other than MS were included. A myelin flow
      cytometry assay was used to detect anti-myelin antibody levels which were
      expressed as mean fluorescence intensity (myelin-MFI). MRI outcome measures were
      new or persistent T2 lesions, gadolinium enhancing T1 lesions and brain atrophy
      which were assessed by normalized brain volumes. RESULTS: There was no
      significant difference between myelin-MFI values in serum and CSF between MS
      patients and controls (Mann-Whitney test p=0.19 and p=0.51). Myelin-MFI values in
      CSF were not correlated with number of T2 lesions (Spearman r=-0.023, p=0.85),
      number of gadolinium enhancing T1 lesions (Spearman r=-0.066, p=0.588) or
      normalized brain volume (Spearman r=-0.065, p=0.594). CONCLUSIONS: These results
      do not confirm an association between anti-myelin antibody reactivity and the
      presence of MS or MRI measures of disease activity.

PMID- 22858372
TI  - Systematic discovery of synergistic novel antibiotic combinations targeting
      multidrug-resistant Acinetobacter baumannii.

PMID- 22858373
TI  - Probiotics for infectious diseases: more drugs, less dietary supplementation.
AB  - According to current definitions, probiotics are live microorganisms that, when
      ingested in adequate quantities, exert a health benefit to the host. The action
      of probiotics in the host is exerted by three mechanisms: modulation of the
      content of gut microbiota; maintenance of the integrity of the gut barrier and
      prevention of bacterial translocation; and modulation of the local immune
      response by the gut-associated immune system. Regarding their role for the
      prevention and treatment of infectious diseases, adequate evidence coming from
      randomised clinical trials (RCTs) is available for antibiotic-associated
      diarrhoea (AAD), Clostridium difficile infection (CDI), acute gastroenteritis and
      infectious complications following admission to the Intensive Care Unit (ICU).
      Existing evidence supports their role for decreasing the incidence of AAD and CDI
      when administered in parallel with antimicrobials. They also shorten the duration
      of symptoms when administered in paediatric populations with acute
      gastroenteritis, particularly of rotavirus aetiology. Available evidence is not
      sufficient to support administration for the management of CDI. Regarding
      populations of critically ill patients, data from many RCTs suggest a decrease of
      infectious complications by starting feeding with probiotics following ICU
      admission, with the exception of patients suffering from severe pancreatitis.
      However, it should be underscored that all analysed RCTs are characterised by
      marked heterogeneity regarding the type of administered probiotic species,
      precluding robust recommendations.

PMID- 22858374
TI  - A single-step kit formulation for the (99m)Tc-labeling of HYNIC-Duramycin.
AB  - INTRODUCTION: (99m)Tc-Duramycin is a unique radiopharmaceutical that binds
      specifically to phosphatidylethanolamine (PE). The current effort is to develop a
      single-step kit formulation for the (99m)Tc labeling of HYNIC-Duramycin. METHODS:
      A titration series of Tricine/TPPTS coligand systems were tested for an optimal
      formulation to produce (99m)Tc-Duramycin with high radiochemical purity and
      specific activity. The radiopharmaceutical prepared using the kit formulation was
      tested for PE binding specificity using polystyrene microbeads coated with
      different phospholipid species. Radiochemical performance of the kits was
      assessed after storage at -20 degrees C, room temperature and 37 degrees C.
      Biodistribution profile of kit-prepared (99m)Tc-Duramycin was characterized in
      healthy rats at 3, 10, 20, 60 and 180min after intravenous injection. Binding
      studies were performed using the rat aortic arch and a rat model of myocardial
      ischemia/reperfusion, which represent scenarios of physiological and pathological
      PE externalization. RESULTS: A Tricine/TPPTS ratio of 10:1 led to a consistent
      production of (99m)Tc-Duramycin with high radiochemical purity (> 90%), whereas a
      higher ratio at 40:1 produced radiopharmaceuticals with incomplete substitution
      of Tricine coligand. (99m)Tc-Duramycin prepared using the single-step kit
      formulation retained PE-binding specificity. The kits are stable over long-term
      storage. The biodistribution profile of kit-prepared (99m)Tc-Duramycin is
      consistent with HPLC purified radiopharmaceutical from prior studies. Binding
      studies on a tissue level indicate that the radiopharmaceutical is suitable for
      studying biological processes that involve PE distribution and redistribution in
      various physiological and pathological conditions. CONCLUSION: A single-step kit
      formulation is developed for (99m)Tc-labeling of HYNIC-Duramycin. The
      radiopharmaceutical has high radiochemical purity and specific activity, retained
      PE binding activities, amiable to long-term storage, and is injection-ready for
      in vivo applications.

PMID- 22858375
TI  - The economic burden of epilepsy in a sample of people with epilepsy in China.
AB  - PURPOSE: Epilepsy causes a significant burden to both patients as well as
      society. The primary aim of this study was to calculate the factual excess costs
      of epilepsy in China in order to provide essential information regarding the
      treatment of the epilepsy for both individuals and society as a whole. METHODS:
      This study was performed on a retrospective cohort of medically treated patients.
      Data collected from 500 patients were analyzed in a standardized format, and
      included clinical characteristics, utilization of sources as well as the
      associated costs of epilepsy. RESULTS: Based on our analyses, a modest estimate
      of the direct cost of epilepsy in China is roughly RMB 3860 (USD 594) per person
      per year. The main expenditures included treatment cost followed by the cost of
      living and inpatient care. The cost of informal treatment accounted for roughly
      41% of all costs. The excess expenditures were similar for gender and the living
      place; however, our findings suggest that the composition proportions were
      different. CONCLUSION: Our findings demonstrate that epilepsy has a significant
      impact on individual medical expenditure, and places a heavy economic burden to
      both patients and the nation of China. Therefore, appropriate treatment and
      management of epilepsy must be assessed not only to increase quality of life, but
      also to consider the financial implications of the prescribed treatments for this
      disease.

PMID- 22858376
TI  - Africa: continent of genome contrasts with implications for biomedical research
      and health.
AB  - The genomic architecture of African populations is poorly understood and there is
      considerable variation between ethno-linguistic groups. Genome-wide approaches
      have been extensively applied to search for genetic associations to complex
      traits in Europeans, but rarely in Africans. This is largely attributed to lower
      levels of funding, poor infrastructure and public health systems, and to the
      small pool of trained scientists. High levels of genetic variation and underlying
      population structure in Africans present significant challenges, but lower levels
      of linkage disequilibrium provide an opportunity for more effective localisation
      of causal variants. High throughput technologies, including dense genotyping
      arrays, genome sequencing and epigenome studies, together with plummeting costs,
      are making research more affordable, even for African scientists. Understanding
      the interactions between genome structure and environmental influences is
      essential to interpreting their contributions to the increase in infectious
      diseases and non-communicable diseases, exacerbated by adverse environments and
      lifestyle choices. The unique genome dynamics in African populations have an
      important role to play in understanding human health and susceptibility to
      disease.

PMID- 22858377
TI  - Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance: NUPR1
      and p21 in chemoresistance.
AB  - The expression of Nuclear Protein 1 (NUPR1) is associated with chemoresistance in
      multiple malignancies. We previously reported that NUPR1 functions as a
      transcriptional cofactor for the p300-p53 complex and transcriptionally regulates
      p21 expression. In the present study we investigated the activity of NUPR1 in p53
      deficient, triple-negative, inflammatory SUM159 breast cancer cells. Our studies
      reveal that NUPR1 confers growth benefit and chemoresistance by causing Akt
      mediated phosphorylation and subsequent cytoplasmic re-localization of p21 and
      activation of the anti-apoptotic Bcl-xL protein. Our findings elucidate a NUPR1
      PI-3-K/Akt-phospho-p21 axis that functions in p53-negative, inflammatory breast
      cancer cells to enhance chemoresistance in breast cancer.

PMID- 22858378
TI  - Transglutaminase-mediated transamidation of serotonin, dopamine and noradrenaline
      to fibronectin: evidence for a general mechanism of monoaminylation.
AB  - The activity of some small GTPases is regulated by covalent transamidation of
      serotonin (5-hydropxytryptamien) to glutamine residues of the enzymes. This
      process is mediated by transglutaminase (TGase) and is termed "serotonylation".
      In addition, serotonylation of neural proteins and proteins of the extracellular
      matrix such as fibronectin has been demonstrated. Here we show that the
      catecholamines dopamine (DA) and noradrenaline (NA) inhibit serotonylation of
      fibronectin and that DA and NA themselves can be selectively transamidated into
      fibronectin by TGase. All three biogenic monoamines also block TGase-mediated
      transamidation of another monoamine, monodansylacadaverine, into fibronectin,
      suggesting a general mechanism of TGase-mediated "monoaminylation".

PMID- 22858379
TI  - Advances in the evaluation of the neonatal brain.

PMID- 22858380
TI  - Neurodevelopment evaluation in children with congenital hypothyroidism by Bayley
      III.
AB  - BACKGROUND: Congenital hypothyroidism is the most common reason of mental
      retardation, and normal neurological development can be provided by early and
      effective treatment. In this present study, it is aimed to compare neurological
      developments of patients in 6-42 months of age with congenital hypothyroidism and
      healthy controls of the same age group prospectively by Bayley III test. METHODS:
      In this present study, neurological developments of 41 congenital hypothyroidism
      cases and 39 healthy controls, who applied to Pediatric Endocrinology Section of
      Mersin Children Hospital and Pediatric Neurology Outpatient Clinic of the Medical
      School at Mersin University between years 2009 and 2011, were evaluated by Bayley
      III test. RESULTS: Cognitive, language and global motor scores in addition to
      receptive communication, expressive communication, fine motor and gross motor
      subscores in children with congenital hypothyroidism were statistically
      significantly lower than those in the control group (p<0.05). It is detected that
      initiation dose and day of treatments, severity of hypothyroidism and time to
      normalization thyroid stimulating hormone had no statistically significant
      effects on neurological development of the study group (p>0.05). In both groups,
      as the education levels of mothers are increased, language development scores are
      also increased (p<0.05). Additionally, statistically significant increases in
      Bayley III scores except cognitive scores have been observed in both groups as
      the level of income is increased (p<0.05). CONCLUSIONS: Despite early and
      effective treatment in newborns with congenital hypothyroidism, retardation in
      neurological developmental has been detected. This situation can be related to
      influences on neurodevelopment in intrauterine period. According to our present
      knowledge, this study is the first case-control study in the literature that
      neurological developments of congenital hypothyroidism patients are evaluated
      with Bayley-III score.

PMID- 22858381
TI  - Disparities in mortality after blunt injury: does insurance type matter?
AB  - BACKGROUND: Insurance-related outcomes disparities are well-known, but
      associations between distinct insurance types and trauma outcomes remain unclear.
      Prior studies have generally merged various insurance types into broad groups.
      The purpose of this study is to determine the association of specific insurance
      types with mortality after blunt injury. MATERIALS AND METHODS: Cases of blunt
      injury among adults aged 18-64 y with an injury severity score >9 were identified
      using the 2007-2009 National Trauma Data Bank. Crude mortality was calculated for
      10 insurance types. Multivariable logistic regression was employed to determine
      difference in odds of death between insurance types, controlling for injury
      severity score, Glasgow Coma Scale motor, mechanism of injury, sex, race, and
      hypotension. Clustering was used to account for possible inter-facility
      variations. RESULTS: A total of 312,312 cases met inclusion criteria. Crude
      mortality ranged from 3.2 to 6.0% by insurance type. Private Insurance, Blue
      Cross Blue Shield, Workers Compensation, and Medicaid yielded the lowest relative
      odds of death, while Not Billed and Self Pay yielded the highest. Compared with
      Private Insurance, odds of death were higher for No Fault (OR 1.25, P = 0.022),
      Not Billed (OR 1.77, P < 0.001), and Self Pay (OR 1.77, P < 0.001). Odds of death
      were higher for Medicare (OR 1.52, P < 0.001) and Other Government (OR 1.35, P =
      0.049), while odds of death were lower for Medicaid (OR 0.89, P = 0.015).
      CONCLUSIONS: Significant differences in mortality after blunt injury were seen
      between insurance types, even among those commonly grouped in other studies.
      Policymakers may use this information to implement programs to monitor and reduce
      insurance-related disparities.

PMID- 22858382
TI  - Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4.
AB  - Yessotoxin (YTX) and okadaic acid (OA), algal toxins accumulated in edible
      shellfish, were previously shown to induce a specific and reversible T Cell
      Receptor (TCR) down-regulation in T lymphocyte EL-4 cells, in a time and
      concentration-dependent manner, via protein kinase C (PKC) and serine/threonine
      protein phosphatase 2A (PP2A) activities. In this study we have evaluated the
      development of other signs of toxicity induced by low concentrations of YTX or OA
      for 3 days of treatment. Concentrations of YTX as low as 1 nM decreased a 35% the
      concentration of viable cells after 48 h exposure to the toxin, while
      concentrations as little as 5 nM YTX or OA were sufficient to induce membrane
      blebbing. The concentration of YTX that produced after 24 h of incubation a 50%
      reduction in maximum cell viability (EC5024) was approximately 46 nM, whereas
      with OA over 75% of the cells were still viable after exposure to 100 nM OA.
      According to our results, the cytoskeleton of EL-4 cells seems to be a cell
      component particularly sensitive to YTX and OA with disruption of F-actin
      cytoskeleton in these cells treated with concentrations of YTX or OA as low as 5
      nM at 48 h incubation. Toxicity by YTX or OA involved typical hallmarks of
      apoptosis and an increase of reactive oxygen species (ROS) production. The
      cytotoxic effects of YTX and OA reported here, and the previously demonstrated
      potential of these toxins to regulate the activity of EL-4 cells through the
      regulation of TCR expression, rise reasonable concern about possible risks for
      human health associated to the chronic exposure to low amounts of YTX or OA
      itself or enhanced by the presence of other shellfish toxins specially by a
      population potentially at risk such as immunocompromised patients.

PMID- 22858383
TI  - The impact of electrocautery method on post-operative bleeding complications
      after non-newborn circumcision and revision circumcision.
AB  - PURPOSE: We evaluated post-operative bleeding complications in non-newborns
      following use of monopolar versus bipolar electrocautery for circumcision or
      revision circumcision. MATERIALS AND METHODS: We retrospectively reviewed
      sequentially performed cases of circumcision and revision circumcision performed
      by nine pediatric urologists at our institution from 2005 to 2010. In order to
      incorporate both the monopolar and bipolar electrocautery experience for a single
      surgeon employing bipolar technique, sequential cases from 2002 to 2010 were
      reviewed. Variables assessed included age, procedure, method of electrocautery,
      skin approximation and dressing, and bleeding complications. RESULTS: 1810
      patients that underwent either circumcision or revision circumcision were
      reviewed. Complete data was available for 1617 patients. Age at operation was a
      mean 3.7 +/- 4.9 yrs and median 1.5 yrs. Return for bleeding complication for all
      surgeons, was 2/336 (0.6%) for bipolar and 28/1281 (2.2%) for monopolar (p =
      0.0545). For the single surgeon using bipolar technique, returns were 2/336
      (0.6%) for bipolar and 5/309 (1.6%) for monopolar (p = 0.2133). Returns per
      procedure type were 1/200 (0.5%) bipolar and 24/844 (2.8%) monopolar for primary
      circumcision (p = 0.0513), and 1/136 (0.7%) bipolar and 4/437 (0.9%) monopolar (p
      = 0.84) for revision. Four of 1617 (0.2%) patients returned to the operating room
      [4/1281 (0.3%) monopolar (p = 0.31)]. There was no difference in return to the
      operating room for circumcision versus revision. CONCLUSION: Return for bleeding
      complications after circumcision and revision circumcision occurred more
      frequently after monopolar electrocautery compared to bipolar. However, there was
      no significant difference between the two electrocautery methods. Either form of
      electrocautery appears to be effective for this common pediatric urologic
      procedure.

PMID- 22858385
TI  - Defibrillation testing: should the paradigm shift?

PMID- 22858384
TI  - Clinical evaluation of defibrillation testing in an unselected population of
      2,120 consecutive patients undergoing first implantable cardioverter
      defibrillator implant.
AB  - OBJECTIVES: The purpose of this study is to assess the effectiveness of
      defibrillation testing (DT) in patients undergoing implantable cardioverter
      defibrillator (ICD) insertion. BACKGROUND: Although DT is considered a standard
      procedure during ICD implantation, its usefulness has not been definitively
      proven. METHODS: The SAFE-ICD (Safety of Two Strategies of ICD Management at
      Implantation) study is a prospective observational study designed to evaluate the
      outcome of 2 strategies: performing defibrillation testing (DT+) versus not
      performing defibrillation testing (DT-) during de novo ICD implants. No deviation
      from the centers' current practice was introduced. In all, 2,120 consecutive
      patients (836 DT+ and 1,284 DT-) age >=18 years were enrolled at 41 Italian
      centers from April 2008 to May 2009 and followed up for 24 months until June
      2011. The primary endpoint was a composite of severe complications at ICD implant
      and sudden cardiac death or resuscitation at 2 years. RESULTS: The primary
      endpoint occurred in 34 patients: 12 intraoperative complications (8 in DT+
      group; 4 in DT- group) and 22 during follow-up (10 in DT+ group; 12 in DT-
      group). Overall, the estimated yearly incidence (95% confidence interval) was DT+
      1.15% (0.73 to 1.83) and DT- 0.68% (0.42 to 1.12). The difference between the 2
      groups was negligible: 0.47% per year (-0.15 to 1.10). Mortality from any cause
      was similar at 2 years (adjusted hazard ratio: 0.97 [0.76 to 1.23], p = 0.80).
      CONCLUSIONS: In this large cohort of new ICD implants, event rates were similar
      and extremely low in both groups. These data indicate a limited clinical
      relevance for DT testing, thus supporting a strategy of omitting DT during an ICD
      implant. (Safety of Two Strategies of ICD Management at Implantation [SAFE-ICD];
      NCT00661037).

PMID- 22858386
TI  - Exercise as medical treatment for depression.

PMID- 22858388
TI  - Cardiovascular disease in the developing world: prevalences, patterns, and the
      potential of early disease detection.
AB  - Over the past decade or more, the prevalence of traditional risk factors for
      atherosclerotic cardiovascular diseases has been increasing in the major populous
      countries of the developing world, including China and India, with consequent
      increases in the rates of coronary and cerebrovascular events. Indeed, by 2020,
      cardiovascular diseases are predicted to be the major causes of morbidity and
      mortality in most developing nations around the world. Techniques for the early
      detection of arterial damage have provided important insights into disease
      patterns and pathogenesis and especially the effects of progressive urbanization
      on cardiovascular risk in these populations. Furthermore, certain other diseases
      affecting the cardiovascular system remain prevalent and important causes of
      cardiovascular morbidity and mortality in developing countries, including the
      cardiac effects of rheumatic heart disease and the vascular effects of malaria.
      Imaging and functional studies of early cardiovascular changes in those disease
      processes have also recently been published by various groups, allowing
      consideration of screening and early treatment opportunities. In this report, the
      authors review the prevalences and patterns of major cardiovascular diseases in
      the developing world, as well as potential opportunities provided by early
      disease detection.

PMID- 22858387
TI  - Exercise and pharmacological treatment of depressive symptoms in patients with
      coronary heart disease: results from the UPBEAT (Understanding the Prognostic
      Benefits of Exercise and Antidepressant Therapy) study.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of exercise and
      antidepressant medication in reducing depressive symptoms and improving
      cardiovascular biomarkers in depressed patients with coronary heart disease.
      BACKGROUND: Although there is good evidence that clinical depression is
      associated with poor prognosis, optimal therapeutic strategies are currently not
      well defined. METHODS: One hundred one outpatients with coronary heart disease
      and elevated depressive symptoms underwent assessment of depression, including a
      psychiatric interview and the Hamilton Rating Scale for Depression. Participants
      were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50
      200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers
      included measures of heart rate variability, endothelial function, baroreflex
      sensitivity, inflammation, and platelet function. RESULTS: After 16 weeks, all
      groups showed improvement on Hamilton Rating Scale for Depression scores.
      Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: 
      9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9)
      groups achieved larger reductions in depressive symptoms compared with those
      receiving placebo (mean -4.5; 95% confidence interval: -7.6 to -1.5; p = 0.034);
      exercise and sertraline were equally effective at reducing depressive symptoms (p
      = 0.607). Exercise and medication tended to result in greater improvements in
      heart rate variability compared with placebo (p = 0.052); exercise tended to
      result in greater improvements in heart rate variability compared with sertraline
      (p = 0.093). CONCLUSIONS: Both exercise and sertraline resulted in greater
      reductions in depressive symptoms compared to placebo in patients with coronary
      heart disease. Evidence that active treatments may also improve cardiovascular
      biomarkers suggests that they may have a beneficial effect on clinical outcomes
      as well as on quality of life. (Exercise to Treat Depression in Individuals With
      Coronary Heart Disease; NCT00302068).

PMID- 22858389
TI  - Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction
      scores in patients with atrial fibrillation undergoing anticoagulation: the
      AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in
      patients with atrial fibrillation) study.
AB  - OBJECTIVES: The objective of this study was to compare the predictive performance
      of bleeding risk-estimation tools in a cohort of patients with atrial
      fibrillation (AF) undergoing anticoagulation. BACKGROUND: Three bleeding risk
      prediction schemes have been derived for and validated in patients with AF:
      HEMORR(2)HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age,
      Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic
      Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors
      in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver
      Function, Stroke, Bleeding History or Predisposition, Labile International
      Normalized Ratio, Elderly, Drugs/Alcohol). Tauhe relative predictive values of
      these bleeding scores have not previously been compared. METHODS: We analyzed the
      dataset from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or
      Acenocoumarol in Patients With Atrial Fibrillation) trial, a multicenter,
      randomized, open-label noninferiority study that compared fixed-dose idraparinux
      with adjustable-dose oral vitamin K antagonist therapy in patients with AF. The
      principal safety outcome was any clinically relevant bleeding event, which was a
      composite of major bleeding plus clinically relevant nonmajor bleeding. RESULTS:
      The HAS-BLED score performed best in predicting any clinically relevant bleeding,
      reflected both in net reclassification improvement (10.3% and 13% improvement
      compared with HEMORR(2)HAGES and ATRIA, respectively) and receiver-operating
      characteristic (ROC) analyses (c-indexes: 0.60 vs. 0.55 and 0.50 for HAS-BLED vs.
      HEMORR(2)AGES and ATRIA, respectively). Using decision-curve analysis, the HAS
      BLED score demonstrated superior performance compared with ATRIA and
      HEMORR(2)HAGES at any threshold probability for clinically relevant bleeding. HAS
      BLED was the only score that demonstrated a significant predictive performance
      for intracranial hemorrhage (c-index: 0.75; p = 0.03). An ATRIA score >3 was not
      significantly associated with the risk for any clinically relevant bleeding on
      Cox regression or on ROC analysis (c-index: 0.50; p = 0.87). CONCLUSIONS: All 3
      tested bleeding risk-prediction scores demonstrated only modest performance in
      predicting any clinically relevant bleeding, although the HAS-BLED score
      performed better than the HEMORR(2)HAGES and ATRIA scores, as reflected by ROC
      analysis, reclassification analysis, and decision-curve analysis. Only HAS-BLED
      demonstrated a significant predictive performance for intracranial hemorrhage.
      Given its simplicity, the HAS-BLED score may be an attractive method for the
      estimation of oral anticoagulant-related bleeding risk for use in clinical
      practice, supporting recommendations in international guidelines.

PMID- 22858390
TI  - Radial versus femoral randomized investigation in ST-segment elevation acute
      coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized
      Investigation in ST-Elevation Acute Coronary Syndrome) study.
AB  - OBJECTIVES: The purpose of this study was to assess whether transradial access
      for ST-segment elevation acute coronary syndrome undergoing early invasive
      treatment is associated with better outcome compared with conventional
      transfemoral access. BACKGROUND: In patients with acute coronary syndrome,
      bleeding is a significant predictor of worse outcome. Access site complications
      represent a significant source of bleeding for those patients undergoing
      revascularization, especially when femoral access is used. METHODS: The RIFLE
      STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute
      Coronary Syndrome) was a multicenter, randomized, parallel-group study. Between
      January 2009 and July 2011, 1,001 acute ST-segment elevation acute coronary
      syndrome patients undergoing primary/rescue percutaneous coronary intervention
      were randomized to the radial (500) or femoral (501) approach at 4 high-volume
      centers. The primary endpoint was the 30-day rate of net adverse clinical events
      (NACEs), defined as a composite of cardiac death, stroke, myocardial infarction,
      target lesion revascularization, and bleeding). Individual components of NACEs
      and length of hospital stay were secondary endpoints. RESULTS: The primary
      endpoint of 30-day NACEs occurred in 68 patients (13.6%) in the radial arm and
      105 patients (21.0%) in the femoral arm (p = 0.003). In particular, compared with
      femoral, radial access was associated with significantly lower rates of cardiac
      mortality (5.2% vs. 9.2%, p = 0.020), bleeding (7.8% vs. 12.2%, p = 0.026), and
      shorter hospital stay (5 days first to third quartile range, 4 to 7 days] vs. 6
      [range, 5 to 8 days]; p = 0.03). CONCLUSIONS: Radial access in patients with ST
      segment elevation acute coronary syndrome is associated with significant clinical
      benefits, in terms of both lower morbidity and cardiac mortality. Thus, it should
      become the recommended approach in these patients, provided adequate operator and
      center expertise is present. (Radial Versus Femoral Investigation in ST Elevation
      Acute Coronary Syndrome [RIFLE-STEACS]; NCT01420614).

PMID- 22858395
TI  - Lysozyme transport in p-HEMA hydrogel contact lenses.
AB  - Protein binding in hydrogels adversely affects their performance and can
      interfere with their usage in several biomedical applications including contact
      lenses. In this study we focus on understanding and modeling the mechanisms of
      protein transport in hydrogels, specifically focusing on the effect of protein
      concentration and gel crosslinking on transport. Specifically, we focus on
      lysozyme, the most abundant protein in tear fluid, and hydrogels of poly
      hydroxyethyl methacrylate (p-HEMA), a common contact lens material. Protein
      uptake experiments with gels of different thicknesses showed a time scale
      increase as the square of the thickness suggesting diffusion controlled
      transport. Partition coefficient was found to be dependent on the equilibrium
      concentration of lysozyme, and also on the degree of crosslinking. Since
      transport is related to mesh size, gel modulus was obtained for various
      crosslinkings and utilized to estimate the mesh size. The transport data were
      fitted to a diffusion model and the fitted diffusivity was compared to
      diffusivity predicted from a model based on hydrogel mesh size. Both protein
      absorption and desorption data fitted the diffusion model with the same value of
      diffusivity, but the experimentally measured diffusivities were significantly
      smaller than those estimated on the basis of the gel mesh size. Models were
      modified to take into account protein binding to the polymer but the modified
      predictions were still larger than the measured values. The results of this study
      could assist in the development of contact lens materials that exhibit minimal
      protein binding, in designing cleaning regimens for protein removal from contact
      lenses, and in applications related to protein binding in several other
      biomaterials.

PMID- 22858396
TI  - Surface molecular imprinting on polypropylene fibers for rhodamine B selective
      adsorption.
AB  - A surface molecular imprinted fiber (MIF-B) for rhodamine B (RhB) was prepared by
      bonding polyethylenimine (PEI) onto polypropylene (PP) fibers and subsequently
      cross-linking with epichlorohydrin (ECH) in the presence of RhB. The chemical
      structures of composites in each synthetic step were traced by FTIR analyses. The
      MIF-B exhibited excellent static and dynamic adsorption properties for RhB. Its
      adsorption isotherm for RhB followed Langmuir model. The competitive adsorption
      results indicated that the MIF-B had much higher selectivity for RhB over a
      structural analog (rhodamine 6G) with a selectivity coefficient (K(c)) of 74.1.
      The MIF-B proved to be a pH-sensitive material. Poly(acrylic acid) (PAA) and PEI
      chains grafted on PP would stretch or shrink in response to pH, resulting in the
      change in size and shape of binding sites of the MIF-B. Basic condition could
      induce the lightly cross-linked MIF-B to swell and expand its surface area, thus
      providing more memory cavities and internal binding sites constructed by
      imprinting process and ultimately leading to higher binding capacity and better
      RhB recognition.

PMID- 22858391
TI  - Genetically-defined metabolic reprogramming in cancer.
AB  - Oncogenes and tumor suppressors regulate cell metabolism. Evidence demonstrates
      that tumorigenic mutations in these genes tend to orchestrate metabolic activity
      into a platform that promotes cell survival, growth, and proliferation. Recent
      work has shown that some metabolic enzymes are also mutated in cancer, and that
      these mutations may influence malignancy directly. Thus, these enzymes seem to
      function as oncogenes and tumor suppressors, and would appear to be compelling
      targets for therapeutic intervention. Here, we review several enzymes mutated in
      cancer - phosphoglycerate dehydrogenase, isocitrate dehydrogenases 1 and 2,
      succinate dehydrogenase, and fumarate hydratase - and discuss exciting new work
      that has begun to pull back the curtain on how mutations in these enzymes
      influence tumorigenesis.

PMID- 22858397
TI  - Nanosilica-supported polyethoxyamines as low-cost, reversible carbon dioxide
      sorbents.
AB  - Novel hybrid quasi-solid-state sorbents pairing inexpensive CO(2)-reactive
      polyethoxyamine (Jeffamine(r)) fluids with an abundantly available silica support
      have been investigated for carbon capture. The highest performance sorbent was
      capable of reversibly capturing close to 70 mg of CO(2) per gram of sorbent at 45
      degrees C, could be almost fully (~90%) regenerated by simple vacuum swing, and
      was stable over many sequential capture-release cycles. The new supports can be
      handled as solventless, free-flowing powders even post-CO(2) capture, obviating
      the mass flow problems arising from viscous liquid (or solid, gel, or wax)
      formation frequently attending carbamate formation. Our results have important
      ramifications for reducing the high costs of thermal regeneration in conventional
      carbon capture schemes, particularly in comparison with the aqueous
      monoethanolamine-based system currently favoured industrially. The strategy of
      uniformly dispersing a functional fluid onto a solid nanosupport in a manner that
      allows intimate contact with and diffusion of external gaseous species is
      additionally projected to find value in a range of gas separation and sensing
      endeavours.

PMID- 22858398
TI  - Functionalization of electropolished titanium surfaces with silane-based self
      assembled monolayers and their application in drug delivery.
AB  - This work reports a novel and reproducible route for the successful modification
      of the surface of titanium (Ti) with self-assembled monolayers (SAMs). By
      electropolishing the surface of Ti, suitable physical/chemical surface properties
      were obtained for adequate growth of OctadecylTrichloroSilane (OTS) based SAM.
      Optimum conditions to achieve a well-organized and densely packed OTS film were
      also determined by monitoring the effect of different parameters including time,
      concentration, and temperature for OTS adsorption. The optimum conditions for the
      formation of an OTS-SAM were found to be upon immersion of the electropolished Ti
      substrate in a 10mM OTS solution at 10 degrees C for 24h. Furthermore, multiple
      growth regimes for the formation of OTS-SAM on electropolished Ti surface were
      observed. The kinetics for the self-assembly were fast at the beginning of OTS
      adsorption, but rapidly slowed down after 10h of immersion, i.e. during the
      densification process of the film at the surface of Ti. In addition, the growth
      behavior was found to be random as opposed to the island growth behavior usually
      observed with OTS at the surface of silica. The successful implementation of OTS
      SAM was further investigated through the immobilization and delivery of a model
      drug and the OTS monolayer showed clear abilities in drug delivery with an
      initial burst release up to 5 days followed by a sustained release up to 26 days.

PMID- 22858399
TI  - Modeling adsorption rate of organic micropollutants present in landfill leachates
      onto granular activated carbon.
AB  - The overall adsorption rate of single micropollutants present in landfill
      leachates such as phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA),
      2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2-methylphenoxyacetic acid
      (MCPA) on two commercial activated carbons was studied. The experimental data
      obtained were interpreted by using a diffusional model (PVSDM) that considers
      external mass transport, intraparticle diffusion, and adsorption on an active
      site. Furthermore, the concentration decay data were interpreted by using
      kinetics models. Results revealed that PVSDM model satisfactorily fitted the
      experimental data of adsorption rate on activated carbon. The tortuosity factor
      of the activated carbons used ranged from 2 to 4. The contribution of pore volume
      diffusion represented more than 92% of intraparticle diffusion confirming that
      pore volume diffusion is the controlling mechanism of the overall rate of
      adsorption and surface diffusion can be neglected. The experimental data were
      satisfactorily fitted the kinetic models. The second-order kinetic model was
      better fitted the experimental adsorption data than the first-order model.

PMID- 22858400
TI  - A colloidal route to fabricate hierarchical sticky and non-sticky substrates.
AB  - We present a facile and inexpensive bottom-up colloidal route to prepare sticky
      superhydrophobic surfaces and non-sticky ones. Either spin coating to assemble
      silica microspheres into random multilayered arrays or irreversible adsorption of
      gold nanoparticles is used to manufacture substrates with a single length scale
      roughness. Hierarchical roughness with multiple length scales is achieved by
      decorating the silica spheres with gold nanoparticles. The surface chemistry of
      the silica surfaces is modified by the adsorption of fluoroalkylsilane self
      assembled monolayers, while gold nanoparticles are hydrophobized by
      dodecanethiol. The wetting properties, both static and dynamic, of surfaces in
      relation to the morphology of the substrates are addressed. We demonstrate the
      role of hierarchy in the roughness in converting a sticky into a non-sticky
      superhydrophobic surface and discuss the results in terms of existing models
      describing wetting characteristics.

PMID- 22858401
TI  - Probing the impact of advanced melting and advanced adsorption phenomena on the
      accuracy of pore size distributions from cryoporometry and adsorption using NMR
      relaxometry and diffusometry.
AB  - The accuracy of pore size distributions (PSD) obtained from gas adsorption and
      cryoporometry is compromised by the presence of advanced adsorption and advanced
      melting effects, respectively. In order to improve PSD accuracy, it is necessary
      to know the extent of such effects. In this work cryoporometry and adsorption
      have been combined to study the onset of advanced melting effects in a sample
      partially-saturated with different volumes of condensate, in turn, by pre
      equilibration with different vapour pressures of adsorbate. NMR relaxometry and
      diffusometry have been used to independently study the size and connectivity of
      adsorbed liquid ganglia at different molten fractions. It has been found that the
      onset of significant advanced melting coincided with abrupt changes in levels of
      individual pore-filling and ganglia inter-connections determined by NMR. These
      findings also highlighted where significant advanced adsorption processes were
      occurring, where larger pores were being filled with condensate before smaller
      pores. These studies have enabled the critical pores governing the advanced
      processes to be identified, and the likely errors in PSDs arising from advanced
      effects to be quantified.

PMID- 22858402
TI  - Conformational switching in bis(zinc porphyrin) Langmuir-Schaefer film as an
      effective tool for selectively sensing aromatic amines.
AB  - A conformational switching of bis(zinc octaethylporphyrin) was observed, for the
      first time, in a Langmuir-Schaefer film as a consequence of appropriate host
      guest interactions. The spectral changes are completely reversible and the high
      sensitivity (~20 ppb) and specificity for aromatic amines open up interesting
      prospects of this functional material as a performing sensor for amines.

PMID- 22858403
TI  - Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism
      and mood in women suffering from anorexia nervosa-a pilot study.
AB  - We investigated the effects of the administration of dehydroepiandrosterone
      (DHEA) on weight, bone metabolism, bone density and clinical mood symptoms in
      outpatient Anorexia Nervosa (AN) patients. AN patients (n=26) were double-blindly
      randomized to receive DHEA (100mg) or placebo for 6 months. Outcome measures were
      bone mineral density (BMD) and bone mineral content (BMC) measured by dual energy
      X-ray absorptiometry (DXA) and metabolism indexes, steroid hormones, and mood and
      eating disorder symptoms measured at baseline and at the 3 and 6 months follow-up
      visits. Mood and eating disorder symptoms were assessed monthly by the Beck
      Depression Inventory, Eating Disorder Inventory and Clinical Global Improvement
      Scales. No treatment or treatment by time interaction was observed for any bone
      density measures. Deoxypiridinolyne (DPD) was positively correlated with weight
      (P=0.02). An increase in body mass index (BMI) in the DHEA group was
      significantly higher at 4 months compared to the control group (P=0.05).
      Improvement of mood was significantly correlated with weight only in the DHEA
      group. Despite a significant decrease in DPD, no improvement in bone mineral
      density was detected. However, patients treated with DHEA benefited from a
      significant increase in BMI, which was positively correlated with improvement in
      mood.

PMID- 22858404
TI  - Synchronous metastatic adenoid cystic and squamous cell carcinoma of the cervical
      lymph nodes 31 years after ablation of the primary palatal tumour.
AB  - The coexistence of different types of malignancy in cervical lymph nodes has been
      reported previously. We report the first case, to the best of our knowledge, of
      concurrent metastatic adenoid cystic carcinoma and squamous cell carcinoma (SCC)
      in cervical lymph nodes. A primary SCC developed three decades after treatment
      for adenoid cystic carcinoma of the palate, and the synchronous metastases became
      clinically apparent the following year. The aetiology of the SCC may have been
      related to radiotherapy or smoking. Whether the adenoid cystic carcinoma would
      have remained dormant, or was reactivated after perturbation of host defence
      mechanisms, is not known. 

PMID- 22858405
TI  - Motilin receptor neuropharmacology: revised understanding.
AB  - Although motilin was identified >40 years ago as a gastrointestinal hormone
      capable of stimulating gastric emptying, the relatively recent availability of
      molecular tools and focus on its neuronal activities are now clarifying
      mechanisms of action. In rodents, only motilin receptor pseudogenes are
      identified. In human stomach, facilitation of enteric cholinergic activity is
      identified as the main mechanism by which gastric emptying is increased; some
      motilin agonists act in a prolonged manner, contrasting with motilin itself and
      with studies using recombinant receptors. As such, assays using recombinant
      receptors seem poor predictors of in vivo activity. High-throughput screening
      enabled selective motilin agonists to be identified, which together with enhanced
      understanding into neuromuscular actions of motilin, promises to deliver rational
      treatments of disorders with delayed gastric emptying.

PMID- 22858407
TI  - The BO test 25 years on.

PMID- 22858406
TI  - Pituitary volume in first-episode schizophrenia.
AB  - Pituitary volumes were measured in 55 first-episode schizophrenia patients at a
      baseline timepoint with 38 receiving a followup scan after antipsychotic
      treatment. Fifty-nine healthy volunteers had baseline scans with 34 receiving a
      followup scan. There were no baseline group differences in pituitary volumes or
      changes in volume following antipsychotic treatment.

PMID- 22858408
TI  - JNK/FOXO mediated PeroxiredoxinV expression regulates redox homeostasis during
      Drosophila melanogaster gut infection.
AB  - Innate immunity plays an important role in combating microbial infection in
      animals. During bacterial infection in Drosophila melanogaster gut, Dual oxidase
      (Duox) generates reactive oxygen species (ROS) to fight against the infected
      microbes. Concurrently, antioxidant systems eliminate residual ROS and protect
      the hosts. Here we found that Drosophila melanogaster Peroxiredoxin V (dPrxV) is
      an immune-related antioxidant enzyme which maintains intestinal redox
      homeostasis. dPrxV was highly expressed in gut and induced by the oral infection
      of Erwinia carotovora carotovora. dPrxV expression was increased by the gut
      specific Duox overexpression but decreased by Duox inhibition. Moreover, dPrxV
      expression was mediated by the JNK/FOXO signaling and dPrxV mutant reduced
      survival after gut infection. These results suggest that JNK/FOXO mediated dPrxV
      expression plays a critical role in Drosophila melanogaster gut during bacterial
      infection in protecting the host gut epithelial cells from oxidative damage.

PMID- 22858410
TI  - Porcine CD27: identification, expression and functional aspects in lymphocyte
      subsets in swine.
AB  - Up to now for Swine Workshop Cluster 2 (SWC2) the orthologous human CD molecule
      was unknown. By use of the SWC2-specific mAb b30c7 and a retroviral cDNA
      expression library derived from stimulated porcine peripheral blood mononuclear
      cells we could identify SWC2 as porcine CD27. Phenotypic analyses of lymphocytes
      isolated from blood and lymphatic organs revealed that mature T cells in thymus
      and T cells in the periphery with a naive phenotype were CD27(+). However, within
      CD8alpha(+) T helper and CD8alpha(+) gammadelta T cells also CD27(-) cells were
      present, indicating a down-regulation after antigen contact in vivo. B cells
      lacked CD27 expression, whereas NK cells expressed intermediate levels.
      Furthermore, plate-bound mAb b30c7 showed a costimulatory capacity on CD3
      activated T cells for proliferation, IFN-gamma and TNF-alpha production. Hence,
      our data indicate an important role of porcine CD27 for T-cell differentiation
      and activation as described for humans and mice.

PMID- 22858409
TI  - Identification of a novel CCR7 gene in rainbow trout with differential expression
      in the context of mucosal or systemic infection.
AB  - In mammals, CCR7 is the chemokine receptor for the CCL19 and CCL21 chemokines,
      molecules with a major role in the recruitment of lymphocytes to lymph nodes and
      Peyer's patches in the intestinal mucosa, especially naive T lymphocytes. In the
      current work, we have identified a CCR7 orthologue in rainbow trout (Oncorhynchus
      mykiss) that shares many of the conserved features of mammalian CCR7. The
      receptor is constitutively transcribed in the gills, hindgut, spleen, thymus and
      gonad. When leukocyte populations were isolated, IgM(+) cells, T cells and
      myeloid cells from head kidney transcribed the CCR7 gene. In blood, both IgM(+)
      and IgT(+) B cells and myeloid cells but not T lymphocytes were transcribing
      CCR7, whereas in the spleen, CCR7 mRNA expression was strongly detected in T
      lymphocytes. In response to infection with viral hemorrhagic septicemia virus
      (VHSV), CCR7 transcription was down-regulated in spleen and head kidney upon
      intraperitoneal infection, whereas upon bath infection, CCR7 was up-regulated in
      gills but remained undetected in the fin bases, the main site of virus entry.
      Concerning its regulation in the intestinal mucosa, the ex vivo stimulation of
      hindgut segments with Poly I:C or inactivated bacteria significantly increased
      CCR7 transcription, while in the context of an infection with Ceratomyxa shasta,
      the levels of transcription of CCR7 in both IgM(+) and IgT(+) cells from the gut
      were dramatically increased. All these data suggest that CCR7 plays an important
      role in lymphocyte trafficking during rainbow trout infections, in which CCR7
      appears to be implicated in the recruitment of B lymphocytes into the gut.

PMID- 22858411
TI  - Manduca sexta gloverin binds microbial components and is active against bacteria
      and fungi.
AB  - Hyalophora gloveri gloverin is a glycine-rich and heat stable antimicrobial
      protein with activity mainly against Escherichia coli. However, Spodoptera exigua
      gloverin is active against a Gram-positive bacterium but inactive against E.
      coli. In this study, we investigated expression profile, binding ability and
      antimicrobial activity of Manduca sexta gloverin (MsGlv). Msglv transcript was
      detected in several tissues of naive larvae with higher levels in the midgut and
      testis. Expression of Msglv mRNA in larvae was up-regulated by active Spatzle
      C108 and peptidoglycans (PGs) of E. coli and Staphylococcus aureus, and the
      activation was blocked by pre-injection of antibody to M. sexta Toll, suggesting
      that Msglv expression is regulated by the Toll-Spatzle pathway. Recombinant MsGlv
      bound to the O-specific antigen and outer core carbohydrate of lipopolysaccharide
      (LPS), Gram-positive lipoteichoic acid (LTA) and PG, and laminarin, but not to E.
      coli PG or mannan. MsGlv was active against Bacillus cereus, Saccharomyces
      cerevisiae and Cryptococcus neoformans, but was almost inactive against E. coli
      and S. aureus. Our results suggest that gloverins are active against some
      bacteria and fungi.

PMID- 22858412
TI  - The bioactivity of teleost IL-6: IL-6 protein in orange-spotted grouper
      (Epinephelus coioides) induces Th2 cell differentiation pathway and antibody
      production.
AB  - Interleukin 6 (IL-6) is a protein secreted by T cells and macrophages and plays
      an important role in immune response. IL-6 regulates the proliferation and
      differentiation of T cells, and elicits immunoglobulin production in B cells. In
      this study, the cDNA il-6 (gil-6) sequence of the orange spotted grouper
      (Epinephelus coioides) was obtained. The deduced IL-6 (gIL-6) protein comprised
      223 amino acids, the sequence shared approximately 30% similarity with mammalian
      IL-6, and between 47% and 69% similarity with other available teleost IL-6. The
      protein comprises the signal peptide, the IL-6 family signature, and conserved
      amino acid residues found in IL-6 sequences of other teleost. In order to
      understand the bioactivity and influence of gIL-6 on humoral immune response,
      recombinant gIL-6 (rgIL-6) synthesized by prokaryotes was injected into orange
      spotted groupers, and the immune-related gene expression at various times in
      various organs was observed. Our results revealed that the Th1 specific
      transcription factor t-bet was down-regulated and Th2 specific transcription
      factors gata3, and c-maf were up-regulated in immune organs, following IL-6
      stimulation. Additionally, higher levels of igm mRNA and translated protein were
      detected in rgIL-6 stimulated fish. These results indicate that IL-6 in groupers
      regulates the differentiation of naive T helper cells into Th2 cells and elicits
      the production of antibodies.

PMID- 22858413
TI  - Water consumption patterns and factors contributing to water consumption in
      arsenic affected population of rural West Bengal, India.
AB  - A direct water intake study was conducted for one year, involving 423 individuals
      from three arsenic (As) affected villages of West Bengal, India. Average direct
      water intake per person and per unit body weight was found to be 3.12+/-1.17
      L/day and 78.07+/-47.08 mL/kg/day (+/- SD), respectively. Average direct water
      intakes for adult males, adult females and children (age <15 years) were 3.95,
      3.03 and 2.14 L/day, respectively. Significant sex differentials were observed
      between ages 16-55 years. For all participants, a sharp increase in water intake
      up to 15 years of age was observed followed by a plateau at a higher intake
      level. Significant monthly, seasonal, regional, and occupational variability was
      also observed. Another study involving 413 subjects determined the amount of
      indirect water intake. Average indirect water intake per person was 1.80+/-0.64
      L/day; for adult males, adult females and children, intake was 2.15, 1.81, and
      1.10 L/day, respectively. Average total (direct + indirect) water intake was 4.92
      L/person/day; for adult males, adult females and children, total intake was 6.10,
      4.84, and 3.24 L/person/day, respectively. The overall contribution of indirect
      water intake to total water consumption was 36.6% for all participants. This
      study additionally elucidated several factors that contribute to variable water
      intake, which can lead to better risk characterization of subpopulations and
      water contaminant ingestion. The study reveals that the water intake rates in the
      three studied populations in West Bengal are greater than the assumed water
      intake rates utilized by the World Health Organization (WHO) in the establishment
      of drinking water quality guidelines; therefore, these assumed intake values may
      be inappropriate for the study population as well as similar ones.

PMID- 22858415
TI  - The effects of communicating uncertainty in quantitative health risk estimates.
AB  - OBJECTIVE: To examine the effects of communicating uncertainty in quantitative
      health risk estimates on participants' understanding, risk perception and
      perceived credibility of risk information source. METHODS: 120 first year
      psychology students were given a hypothetical health-care scenario, with source
      of risk information (clinician, pharmaceutical company) varied between subjects
      and uncertainty (point, small range and large range risk estimate format) varied
      within subjects. RESULTS: The communication of uncertainty in the form of both a
      small and large range resulted in a reduction in accurate understanding and
      increased perceptions of risk when a large range was communicated compared to a
      point estimate. It also reduced perceptions of credibility of the information
      source, though for the clinician this was only the case when a large range was
      presented. CONCLUSIONS: The findings suggest that even for highly educated
      adults, communicating uncertainty as a range risk estimate has the potential to
      negatively affect understanding, increase risk perceptions and decrease perceived
      credibility. PRACTICE IMPLICATIONS: Communicating uncertainty in risk using a
      numeric range should be carefully considered by health-care providers. More
      research is needed to develop alternative strategies to effectively communicate
      the uncertainty in health risks to consumers.

PMID- 22858414
TI  - Cancer heterogeneity: origins and implications for genetic association studies.
AB  - Genetic association studies have become standard approaches to characterize the
      genetic and epigenetic variability associated with cancer development, including
      predispositions and mutations. However, the bewildering genetic and phenotypic
      heterogeneity inherent in cancer both magnifies the conceptual and methodological
      problems associated with these approaches and renders difficult the translation
      of available genetic information into a knowledge that is both biologically sound
      and clinically relevant. Here, we elaborate on the underlying causes of this
      complexity, illustrate why it represents a challenge for genetic association
      studies, and briefly discuss how it can be reconciled with the ultimate goals of
      identifying targetable disease pathways and successfully treating individual
      patients.

PMID- 22858416
TI  - Shelter from the storm; men with chronic pain and narratives from the
      rehabilitation clinic.
AB  - OBJECTIVE: To examine the meaning of participating at a rehabilitation clinic in
      the lives of men with chronic pain. METHODS: The material consists of qualitative
      interviews with 10 Norwegian men with chronic neck pain, and was analyzed using
      narrative method, combined with a gender sensitive perspective. RESULTS: With
      references to 'identification of a cause' and 'rebuilding physical strength', the
      significance of medical expertise initially seemed to be linked to restoring
      bodily function. In the men's individual lives, however, the meaning of being in
      rehabilitation extended far beyond achieving manifest treatment goals and was
      also linked to profound human needs, such as to (re)build a self, to be comforted
      and connected to others. CONCLUSION: As rehabilitation clinics may provide a
      legitimate space in which men's experiences of pain are 'housed', they may
      constitute significant sources for restitution work, as well as significant
      shelters against social accusation that they are not really sick. PRACTICE
      IMPLICATIONS: We suggest that health professionals should be aware of the social
      significance rehabilitation clinics may represent for men living with chronic
      pain.

PMID- 22858417
TI  - Changes in regional brain volume three months after stroke.
AB  - INTRODUCTION: Little is known about changes in regional brain volume after
      stroke. We investigated cortical thickness changes over 3 months in a group of
      stroke patients compared with controls. MATERIAL AND METHODS: Patients with acute
      hemispheric stroke were studied within 3h of stroke onset and serially over 3
      months. We compared the acute and 3 month scans with independently acquired
      control images. High resolution isotropic T1 images were analyzed using
      FreeSurfer V5.0, comparing regional average cortical thickness, hippocampal and
      thalamic volumes. Stroke patient results were analyzed separately for
      ipsilesional and contralesional regions, whereas control results were averaged
      across hemisphere. Percentage change scores between the two time points were
      computed for each participant, and paired sample t-tests were used to assess
      significant change. RESULTS: 12 stroke patients (9 men, 7 left-hemispheric, mean
      age=65.1 years) and 10 control participants (5 men, mean age=67.2 years) were
      included. There were no significant differences between the 2 time points in
      global or regional average cortical thickness, or hippocampal and thalamic volume
      estimates for control subjects. Regional variability in patient data was
      demonstrated, particularly cortical thickness increases in contralesional
      paracentral, superior frontal and insular regions, areas known to be activated in
      functional MRI studies of motor recovery. A significant reduction in thalamic
      volume was also found, most apparent ipsilesionally. CONCLUSIONS: Post-stroke
      changes in regional cortical thickness are demonstrable even over short time
      frames. Contralesional cortical thickness increases may represent compensatory
      mechanisms. Significant reductions in thalamic volume may represent evidence of
      early post-stroke atrophy. Further studies are required to confirm and extend
      these preliminary results.

PMID- 22858418
TI  - Olfactory function and alternation learning in eating disorders.
AB  - Orbitofrontal dysfunction is a prominent feature of obsessive compulsive disorder
      (OCD). In the present study we assessed orbitofrontal functioning in eating
      disorders (EDs) which share many features with OCD. For this purpose we studied
      female adolescent inpatients with anorexia nervosa restricting type (n=40),
      anorexia nervosa binge/purge type (n=23), a normal weight group including
      patients with either bulimia nervosa or eating disorder not otherwise specified
      purging type (n=33), and 20 non-ED control females. Patients were assessed at
      admission, and when achieving weight restoration and symptom stabilization at
      discharge, for depression, non-ED, and ED-related OC symptoms. Orbitofrontal
      functioning was assessed with an alternation learning task, and with a battery
      assessing olfactory threshold and discrimination. Control females were assessed
      once. ED patients of all subtypes performed better on olfactory threshold and
      discrimination, but not on alternation learning, in comparison to healthy
      controls. More favorable orbitofrontal functioning was associated with greater ED
      related obsessionality. No changes were found in olfactory threshold and
      discrimination between acutely-ill and symptomatically-stabilized patients. The
      improvement shown in alternation learning from admission to discharge was
      suggested to reflect a learning effect rather than being an actual change. Our
      findings suggest that the better orbitofrontal functioning of ED patients in
      comparison to healthy controls may represent a core feature of the ED that is
      independent of malnutrition and deranged eating behaviors, but is associated with
      ED-related obsessionality.

PMID- 22858419
TI  - Pathological fracture of the mandible in a paediatric patient with congenital
      insensitivity to pain with anhidrosis (CIPA).
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare hereditary
      sensory and autonomic neuropathy (HSAN) characterized by pain, self-mutilating
      behaviour, anhidrosis and recurrent hyperthermia. CIPA has a multisystem
      involvement, including fractures of the extremities with slow healing,
      immunologic abnormalities, and a chronic inflammatory state. The mandible is
      reported to have a higher incidence of osteomyelitis, though mandibular fracture
      among CIPA patients, is very rare, with to our knowledge no reports in children.
      A case of pathological fracture of the mandible in a 6-year-old child with CIPA
      treated by ORIF is reported. In contrast to the slow healing reported in long
      bones, the mandible healed very quickly, possibly indicating that the
      osteoporotic mandible in this group of patients is different from that seen in
      the elderly. Furthermore, the standard ORIF technique can be safely used in this
      rare group.

PMID- 22858420
TI  - Can we improve the detection rate and interobserver agreement in capsule
      endoscopy?
AB  - BACKGROUND: Data about strategies for improving the diagnostic ability of capsule
      endoscopy readers are lacking. AIM: (1) To evaluate the detection rate and the
      interobserver agreement among readers with different experience; (2) to verify
      the impact of a specific training (hands-on training plus expert tutorial) on
      these parameters. METHODS: 17 readers reviewed 12 videos twice; between the two
      readings they underwent the training. The identified small bowel findings were
      described by a simplified version of Structured Terminology and classifies as
      clinically significant/non-significant. Findings identified by the readers were
      compared with those identified by three experts (Reference Standard). RESULTS:
      The Reference Standard identified 26 clinically significant findings. The mean
      detection rate of overall readers for significant findings was low (about 50%)
      and did not change after the training (46.2% and 46.4%, respectively). There was
      no difference in the detection rate among readers with different experience. The
      interobserver agreement with the Reference Standard in describing significant
      findings was moderate (k = 0.44; CI95%: 0.39-0.50) and did not change after the
      training (k = 0.44; CI95%: 0.38-0.49) or stratifying readers according to their
      experience. CONCLUSIONS: Both the interobserver agreement and the detection rate
      of significant findings are low, regardless of the readers' experience. Our
      training did not significantly increase the performance of readers with different
      experience.

PMID- 22858421
TI  - Dynamic and scalable audio classification by collective network of binary
      classifiers framework: an evolutionary approach.
AB  - In this paper, we propose a novel framework based on a collective network of
      evolutionary binary classifiers (CNBC) to address the problems of feature and
      class scalability. The main goal of the proposed framework is to achieve a high
      classification performance over dynamic audio and video repositories. The
      proposed framework adopts a "Divide and Conquer" approach in which an individual
      network of binary classifiers (NBC) is allocated to discriminate each audio
      class. An evolutionary search is applied to find the best binary classifier in
      each NBC with respect to a given criterion. Through the incremental evolution
      sessions, the CNBC framework can dynamically adapt to each new incoming class or
      feature set without resorting to a full-scale re-training or re-configuration.
      Therefore, the CNBC framework is particularly designed for dynamically varying
      databases where no conventional static classifiers can adapt to such changes. In
      short, it is entirely a novel topology, an unprecedented approach for dynamic,
      content/data adaptive and scalable audio classification. A large set of audio
      features can be effectively used in the framework, where the CNBCs make
      appropriate selections and combinations so as to achieve the highest
      discrimination among individual audio classes. Experiments demonstrate a high
      classification accuracy (above 90%) and efficiency of the proposed framework over
      large and dynamic audio databases.

PMID- 22858422
TI  - Darwin's Pangenesis and molecular medicine.
AB  - Based on Hippocrates' pangenetic idea, Darwin elaborated his Pangenesis
      hypothesis to explain a host of phenomena including inherited diseases. The
      conventional wisdom is that Pangenesis is wrong because it explains the
      inheritance of acquired characteristics and no evidence was found to support his
      hypothetical gemmules - molecular carriers of hereditary characteristics. Now,
      growing evidence for the inheritance of acquired characteristics accumulates and
      the discovery of circulating nucleic acids provides evidence for the chemical
      existence of Darwin's gemmules, and a new understanding of Pangenesis brings a
      broader perspective on molecular medicine.

PMID- 22858423
TI  - Allocation of authority in European health policy.
AB  - Although many study the effects of different allocations of health policy
      authority, few ask why countries assign responsibility over different policies as
      they do. We test two broad theories: fiscal federalism, which predicts rational
      governments will concentrate information-intensive operations at lower levels,
      and redistributive and regulatory functions at higher levels; and "politicized
      federalism", which suggests a combination of systematic and historically
      idiosyncratic political variables interfere with efficient allocation of
      authority. Drawing on the WHO Health in Transition country profiles, we present
      new data on the allocation of responsibility for key health care policy tasks
      (implementation, provision, finance, regulation, and framework legislation) and
      policy areas (primary, secondary and tertiary care, public health and
      pharmaceuticals) in the 27 EU member states and Switzerland. We use a Bayesian
      multinomial mixed logit model to analyze how different countries arrive at
      different allocations of authority over each task and area of health policy, and
      find the allocation of powers broadly follows fiscal federalism. Responsibility
      for pharmaceuticals, framework legislation, and most finance lodges at the
      highest levels of government, acute and primary care in the regions, and
      provision at the local and regional levels. Where allocation does not follow
      fiscal federalism, it appears to reflect ethnic divisions, the population of
      states and regions, the presence of mountainous terrain, and the timing of region
      creation.

PMID- 22858424
TI  - Evaluation of control and surveillance strategies for classical swine fever using
      a simulation model.
AB  - Classical swine fever (CSF) outbreaks can cause enormous losses in naive pig
      populations. How to best minimize the economic damage and number of culled
      animals caused by CSF is therefore an important research area. The baseline CSF
      control strategy in the European Union and Switzerland consists of culling all
      animals in infected herds, movement restrictions for animals, material and people
      within a given distance to the infected herd and epidemiological tracing of
      transmission contacts. Additional disease control measures such as pre-emptive
      culling or vaccination have been recommended based on the results from several
      simulation models; however, these models were parameterized for areas with high
      animal densities. The objective of this study was to explore whether pre-emptive
      culling and emergency vaccination should also be recommended in low- to moderate
      density areas such as Switzerland. Additionally, we studied the influence of
      initial outbreak conditions on outbreak severity to improve the efficiency of
      disease prevention and surveillance. A spatial, stochastic, individual-animal
      based simulation model using all registered Swiss pig premises in 2009 (n=9770)
      was implemented to quantify these relationships. The model simulates within-herd
      and between-herd transmission (direct and indirect contacts and local area
      spread). By varying the four parameters (a) control measures, (b) index herd type
      (breeding, fattening, weaning or mixed herd), (c) detection delay for secondary
      cases during an outbreak and (d) contact tracing probability, 112 distinct
      scenarios were simulated. To assess the impact of scenarios on outbreak severity,
      daily transmission rates were compared between scenarios. Compared with the
      baseline strategy (stamping out and movement restrictions) vaccination and pre
      emptive culling neither reduced outbreak size nor duration. Outbreaks starting in
      a herd with weaning piglets or fattening pigs caused higher losses regarding to
      the number of culled premises and were longer lasting than those starting in the
      two other index herd types. Similarly, larger transmission rates were estimated
      for these index herd type outbreaks. A longer detection delay resulted in more
      culled premises and longer duration and better transmission tracing increased the
      number of short outbreaks. Based on the simulation results, baseline control
      strategies seem sufficient to control CSF in low-medium animal-dense areas. Early
      detection of outbreaks is crucial and risk-based surveillance should be focused
      on weaning piglet and fattening pig premises.

PMID- 22858425
TI  - The effectiveness of selected feed and water additives for reducing Salmonella
      spp. of public health importance in broiler chickens: a systematic review, meta
      analysis, and meta-regression approach.
AB  - Eating inappropriately prepared poultry meat is a major cause of foodborne
      salmonellosis. Our objectives were to determine the efficacy of feed and water
      additives (other than competitive exclusion and antimicrobials) on reducing
      Salmonella prevalence or concentration in broiler chickens using systematic
      review-meta-analysis and to explore sources of heterogeneity found in the meta
      analysis through meta-regression. Six electronic databases were searched (Current
      Contents (1999-2009), Agricola (1924-2009), MEDLINE (1860-2009), Scopus (1960
      2009), Centre for Agricultural Bioscience (CAB) (1913-2009), and CAB Global
      Health (1971-2009)), five topic experts were contacted, and the bibliographies of
      review articles and a topic-relevant textbook were manually searched to identify
      all relevant research. Study inclusion criteria comprised: English-language
      primary research investigating the effects of feed and water additives on the
      Salmonella prevalence or concentration in broiler chickens. Data extraction and
      study methodological assessment were conducted by two reviewers independently
      using pretested forms. Seventy challenge studies (n=910 unique treatment-control
      comparisons), seven controlled studies (n=154), and one quasi-experiment (n=1)
      met the inclusion criteria. Compared to an assumed control group prevalence of 44
      of 1000 broilers, random-effects meta-analysis indicated that the Salmonella
      cecal colonization in groups with prebiotics (fructooligosaccharide, lactose,
      whey, dried milk, lactulose, lactosucrose, sucrose, maltose,
      mannanoligosaccharide) added to feed or water was 15 out of 1000 broilers; with
      lactose added to feed or water it was 10 out of 1000 broilers; with experimental
      chlorate product (ECP) added to feed or water it was 21 out of 1000. For ECP the
      concentration of Salmonella in the ceca was decreased by 0.61 log(10)cfu/g in the
      treated group compared to the control group. Significant heterogeneity (Cochran's
      Q-statistic p<=0.10) was observed among studies examining all organic acids
      (controlled or challenge experiments), butyric acid, formic acid, a
      formic/propionic acid mixture, fermented liquid feed, and D-mannose. Meta
      regressions were conducted to examine the source of heterogeneity among studies.
      For prevalence outcomes, 36% and 60% of the total variance was within and between
      studies, respectively. For concentration outcomes, 39% and 33% of the total
      variance was within and between studies, respectively. Inadequate blinding and
      randomization was common, and no studies undergoing meta-analysis or meta
      regression were conducted on a commercial farm. The strength of evidence of the
      effect of these additives was very low. Studies conducted under commercial
      conditions are needed to understand the potential benefit of these interventions
      for the poultry industry and to improve the strength of evidence of the
      effectiveness of these additives.

PMID- 22858426
TI  - Radiotherapy quality assurance: facilitation of radiotherapy research and
      implementation of technology.

PMID- 22858427
TI  - Prospective evaluation of MRI, 11C-acetate PET/CT and contrast-enhanced CT for
      staging of bladder cancer.
AB  - PURPOSE: To prospectively evaluate the diagnostic performance of magnetic
      resonance imaging (MRI), (11)C-acetate positron emission tomography/computed
      tomography (PET/CT) and contrast-enhanced CT for bladder cancer staging, using
      whole-mount pathologic review of radical cystectomy and pelvic lymph node
      specimens as the reference standard. MATERIALS AND METHODS: The institutional
      review board approved this prospective study, which was compliant with the Health
      Insurance Portability and Accountability Act. Written informed consent was
      obtained from 16 patients with histologically confirmed bladder cancer who
      underwent MRI, (11)C-acetate PET/CT and contrast-enhanced CT before radical
      cystectomy and pelvic lymph node dissection. Before imaging 4/16 patients had
      received intravesical Bacillus Calmette-Guerin treatment, 6 had received systemic
      chemotherapy, 3 had received both and 3 had received neither. Measures of
      diagnostic performance including accuracy, sensitivity and specificity were
      estimated separately for each imaging modality. RESULTS: MRI correctly staged 56%
      of patients (9/16), overstaged 38% (6/16) and understaged 6% (1/16). CT correctly
      staged 50% of patients (8/16), overstaged 44% (7/16) and understaged 6% (1/16).
      In 9 patients, (11)C-acetate PET/CT showed uptake within the bladder wall; the
      uptake was true-positive in 7 patients and false-positive in 2 patients. Of the
      remaining 7 patients, 5 had true-negative and 2 had false-negative PET/CT results
      for cancer in the bladder wall. For all modalities, staging accuracy was reduced
      in patients with a history of prior intravesical and/or systemic chemotherapy.
      CONCLUSION: In staging bladder cancer, MRI, (11)C-acetate PET/CT and CT displayed
      similar levels of accuracy. For all modalities, a history of intravesical and/or
      systemic chemotherapy affected staging accuracy.

PMID- 22858428
TI  - Evolutions in food marketing, quantifying the impact, and policy implications.
AB  - A case study on interactive digital marketing examined the adequacy of extant
      policy controls and their underpinning paradigms to constrain the effects of this
      rapidly emerging practice. Findings were interactive digital marketing is
      expanding the strategies available to promote products, brands and consumer
      behaviours. It facilitates relational marketing; the collection of personal data
      for marketing; integration of the marketing mix, and provides a platform for
      consumers to engage in the co-creation of marketing communications. The
      paradigmatic logic of current policies to constrain youth-oriented food marketing
      does not address the interactive nature of digital marketing. The evidence base
      on the effects of HFSS marketing and policy interventions is based on
      conceptualizations of marketing as a force promoting transactions rather than
      interactions. Digital technologies are generating rich consumer data. Interactive
      digital technologies increase the complexity of the task of quantifying the
      impact of marketing. The rapidity of its uptake also increases urgency of need to
      identify appropriate effects measures. Independent analysis of commercial
      consumer data (appropriately transformed to protect commercial confidentiality
      and personal privacy) would provide evidence sources for policy on the impacts of
      commercial food and beverage marketing and policy controls.

PMID- 22858429
TI  - A refined hemispheric model of normal human aortic valve and root geometry.
AB  - BACKGROUND: Better understanding of aortic root geometry could improve diagnosis
      and reconstruction of pathologic aortic valves. In this study, a previous model
      of hemispheric aortic valve leaflets nested within a cylindrical aorta was
      refined in humans with normal aortic valves. METHODS: Using 1-mm axial slices,
      high-resolution computed tomographic angiograms from 10 normal aortic roots were
      used to generate high-density X-, Y-, and Z-coordinates of valve structures using
      Mathematica software. Three-dimensional least squares regression analyses of
      leaflet and sinus coordinates were employed to compare multiple geometric models
      of aortic valve and root geometry. Shapes and dimensions of all root structures
      were evaluated and compared. RESULTS: Aortic valve geometry was roughly
      hemispherical, but the valve base was elliptical (minor-major diameter ratio =
      .66). Dimensional fits of the leaflet-sinus complexes also were better using
      ellipsoidal geometry, with taller leaflets than predicted by hemispheres. The
      commissure between the left and noncoronary cusps was located uniformly at the
      posterior junction of the base minor diameter and circumference, with the center
      of the right coronary cusp opposite. The subcommissural post areas flared outward
      by 5 degrees  to 10 degrees , and the volume of the right coronary leaflet-sinus
      complex was 12.4% and 10.7% larger than the noncoronary cusps and left cusps,
      respectively. CONCLUSIONS: The normal human aortic valve is an elliptical
      structure, and ellipsoidal refinements improve representation of leaflet
      geometry. The left and noncoronary cusps commissure is located posteriorly; the
      right coronary cusp is located anteriorly. This model could be useful in
      quantifying pathologic geometry and in engineering devices for aortic valve
      reconstruction.

PMID- 22858430
TI  - Feasibility of landiolol and bisoprolol for prevention of atrial fibrillation
      after coronary artery bypass grafting: a pilot study.
AB  - BACKGROUND: We previously performed a trial of intravenous landiolol
      hydrochloride during and after cardiac surgery (the PASCAL trial) and
      demonstrated a preventive effect on postoperative atrial fibrillation (AF). In
      the present study, we investigated the efficacy of increasing the dose and
      administration period of landiolol for prevention of postoperative AF, as well as
      the effect of oral bisoprolol in the early postoperative period. PATIENTS AND
      METHODS: A total of 105 patients who underwent coronary artery bypass grafting
      were randomized to 3 groups: a group receiving intravenous landiolol
      perioperatively at 5 MUg/kg/min for 3 days (group L), a group receiving oral
      bisoprolol postoperatively together with landiolol (group LB), and a control
      group without beta-blocker therapy (group C). The primary end point was the
      presence/absence of postoperative AF. Secondary end points were (1) the early
      clinical outcome, (2) hemodynamics, (3) cardiac enzymes (creatine kinase
      isoenzyme MB, troponin-I, and human heart fatty acid-binding protein), (4) high
      sensitivity C-reactive protein (hs-CRP) and pentraxin-3, (5) asymmetric
      dimethylarginine (ADMA), and (6) brain natriuretic peptide. RESULTS:
      Postoperative AF occurred in 14.5% of group L, 9.1% of group LB, and 35.3% of
      group C. A significant difference was observed between groups LB and C.
      Significantly higher levels of troponin-I, human heart fatty acid-binding
      protein, hs-CRP, pentraxin-3, and ADMA were noted in group C than in groups L and
      LB. CONCLUSIONS: Landiolol and bisoprolol prevented postoperative AF. The anti
      ischemic, anti-inflammatory, and anti-oxidant effects of these beta-blockers
      presumably inhibited the onset of AF.

PMID- 22858431
TI  - Effects of computing parameters and measurement locations on the estimation of 3D
      NPS in non-stationary MDCT images.
AB  - The goal of this study was to investigate the impact of computing parameters and
      the location of volumes of interest (VOI) on the calculation of 3D noise power
      spectrum (NPS) in order to determine an optimal set of computing parameters and
      propose a robust method for evaluating the noise properties of imaging systems.
      Noise stationarity in noise volumes acquired with a water phantom on a 128-MDCT
      and a 320-MDCT scanner were analyzed in the spatial domain in order to define
      locally stationary VOIs. The influence of the computing parameters in the 3D NPS
      measurement: the sampling distances bx,y,z and the VOI lengths Lx,y,z, the number
      of VOIs NVOI and the structured noise were investigated to minimize measurement
      errors. The effect of the VOI locations on the NPS was also investigated. Results
      showed that the noise (standard deviation) varies more in the r-direction
      (phantom radius) than z-direction plane. A 25 * 25 * 40 mm(3) VOI associated with
      DFOV = 200 mm (Lx,y,z = 64, bx,y = 0.391 mm with 512 * 512 matrix) and a first
      order detrending method to reduce structured noise led to an accurate NPS
      estimation. NPS estimated from off centered small VOIs had a directional
      dependency contrary to NPS obtained from large VOIs located in the center of the
      volume or from small VOIs located on a concentric circle. This showed that the
      VOI size and location play a major role in the determination of NPS when images
      are not stationary. This study emphasizes the need for consistent measurement
      methods to assess and compare image quality in CT.

PMID- 22858432
TI  - Computed radiographic and ultrasonic evaluation of bone regeneration during
      tibial distraction osteogenesis in rabbits.
AB  - Computed radiography (CR) and a combined ultrasound (US) approach involving two
      dimensional (2-D) and three-dimensional (3-D) ultrasonography with ultrasonometry
      were employed to evaluate their respective efficacies in monitoring bone
      regeneration during rabbit tibial distraction osteogenesis (DO). Results
      demonstrated that 2-D and 3-D ultrasonography depicted bone callus growth changes
      during distraction while CR could not. Evaluation of callus speed of sound,
      acoustic reflection and attenuation showed significant linear changes over time
      during early DO stage (p < 0.05). However, surrogate measure of callus density by
      CR only showed such significant linear changes during consolidation (p < 0.05).
      Also, callus speed of sound and acoustic reflection during early DO stage showed
      strong predictions to the bone mineral density and microstructural properties
      (adjusted-R(2) = 0.43-0.67) of consolidated bone callus measured at the treatment
      end-point by microcomputed tomography. Findings of the present study indicated a
      preferred use of the combined US approach over CR in the early monitoring of bone
      regeneration during DO treatment.

PMID- 22858434
TI  - Re: does the use of an assistive device by nurses impact peripheral intravenous
      catheter insertion success in children?

PMID- 22858435
TI  - Compromised neutrophil function and bovine E. coli mastitis: is C5a the missing
      link?
AB  - During early lactation, dairy cow are prone to developing severe mastitis in
      responses to intramammary Escherichia coli infections. These severe inflammatory
      responses have been correlated with reduced neutrophil function during the
      periparturient period. However, the causative mechanism of neutrophil dysfunction
      has not been elucidated. Studies in murine sepsis models have shown that during
      sepsis neutrophils are functionally paralysed due to the presence of high
      concentrations of complement factor 5a (C5a). In this review, we hypothesize that
      C5a as a critical early mediator in the development of severe E. coli mastitis.
      Furthermore, preliminary data suggest that crosstalk between C5a and TLR4
      signalling in neutrophils may provide a positive feedback mechanism that may be
      involved in the pathogenesis of a severe mastitis response. Finally, we focus on
      the therapeutic potential of disrupting the C5a signalling pathway as an
      important strategy for treatment of severe E. coli mastitis in dairy cattle.

PMID- 22858436
TI  - Submaximal exercise testing predicts perioperative hospitalization after aortic
      aneurysm repair.
AB  - BACKGROUND: Aortic aneurysm repair is a high-risk surgical procedure. Patients
      are often elderly, with multiple comorbidities that predispose them to
      perioperative morbidity. Use of endovascular aneurysm repair (EVAR) has increased
      due to reduced early perioperative risk. This study assessed whether preoperative
      cardiopulmonary exercise testing (CPET) could be used to predict morbidity and
      hospital length of stay (LOS) after aortic aneurysm repair. METHODS: A total of
      185 patients underwent surgical repair (84 open repairs, 101 EVAR) and had
      adequate determination of a submaximal CPET parameter (anaerobic threshold).
      RESULTS: Patient comorbidities and cardiorespiratory fitness, derived from CPET,
      were similar between surgical procedures. Patients undergoing EVAR had fewer
      complications (10% vs 32%; P<.0001) and shorter mean (standard deviation [SD])
      hospital LOS of 5.7 (9.3) days vs 14.4 (10.9) days compared with open repair
      (P<.0001). The hospital LOS was significantly increased in patients with one or
      more complications in both groups compared with those with no complications. In
      the open repair group, the level of fitness, as defined by anaerobic threshold,
      was an independent predictor of postoperative morbidity and hospital LOS. When
      the optimal anaerobic threshold (10 mL/min/kg) derived from receiver operator
      curve analysis was used as a cutoff value, unfit patients stayed significantly
      longer than fit patients in critical care (mean, 6.4 [SD, 6.9] days vs 2.4 [SD,
      2.9] days; P=.002) and in the hospital (mean, 23.1 [SD, 14.8] days vs 11.0 [SD,
      6.1] days; P<.0001). In contrast, fitness in the EVAR group was not predictive of
      postoperative morbidity but did have predictive value for hospital LOS.
      CONCLUSIONS: Cardiorespiratory fitness holds significant clinical value before
      aortic aneurysm repair in predicting postsurgical complications and duration of
      critical care and hospital LOS. Preoperative measurement of fitness could then
      direct clinical management with regard to operative choice, postoperative
      resource allocation, and informed patient decision making.

PMID- 22858437
TI  - An evaluation of current services available for people diagnosed with head and
      neck cancer in the UK (2009-2010).
AB  - AIMS: To evaluate current care and service provision for people with head and
      neck cancer in the UK. MATERIALS AND METHODS: Self-report questionnaires for
      cancer networks, clinical leads of oncology units and leads for multidisciplinary
      teams (MDTs) were designed. These questionnaires were based on a previous survey.
      Questionnaires were sent out between 2009 and 2010. RESULTS: Questionnaires were
      received from all networks (n = 37), most oncology units (48 of 53) and most MDTs
      (51 of 63). Care for people with head and neck cancer is increasingly being
      provided by a centralised MDT. The membership of these teams varies; facilities
      available for team meetings are fit for purpose in most cases. MDTs are meeting
      frequently (weekly meetings in 96%) and discussing on average 18 cases at each
      meeting (95% confidence interval 15-21 cases). Most oncologists have access to
      all common anti-cancer drugs and most have access to all forms of radiotherapy.
      Intensity-modulated radiotherapy is not yet available in some oncology units
      (28%). A small number of units have only one oncologist (13%). Despite audit and
      research being part of the rationale for MDT working, regular discussion of
      morbidity and mortality is unusual (40%) and use of a database to record
      decisions is not universal. Only seven centres record decisions into the Data for
      Head and Neck Oncology database. Reported recruitment to studies is generally low
      (<2% of cases enrolled in studies in 62%). CONCLUSIONS: Head and neck cancer care
      is increasingly provided through a centralised MDT. Increased resources and
      further changes in practice are required to implement current National Health
      Service cancer policy. Teams need to improve recording of their decision-making,
      discuss morbidity and mortality and support recruitment to clinical studies.

PMID- 22858438
TI  - Implementation of stereotactic ablative radiotherapy (stereotactic body
      radiotherapy).

PMID- 22858439
TI  - Bladder cancer radiotherapy margins: a comparison of daily alignment using skin,
      bone or soft tissue.
AB  - AIMS: To determine the clinical target volume (CTV) to planning target volume
      (PTV) margins required for bladder coverage when using skin or bony or soft
      tissue matching on a daily basis. MATERIALS AND METHODS: Twenty-seven patients
      with T2-T4 transitional cell carcinoma of the bladder were treated with daily
      online adaptive image-guided radiotherapy using cone beam computed tomography.
      All daily CTVs were contoured by a single observer. A retrospective comparison of
      coverage of the bladder CTV using skin, bone and soft tissue matching was
      conducted. RESULTS: With the skin set-up, bladder CTV coverage with a margin of
      0.5, 1.0, 1.5, 2.0 and 2.5 cm was 0, 19, 56, 93 and 96%, respectively. For the
      daily set-up based on bone, the respective coverage was 0, 41, 63, 89 and 96%.
      For soft tissue set-up based on the geometric centre of the bladder, coverage was
      52, 89, 96, 100 and 100%, respectively. CONCLUSIONS: Based on coverage of the
      CTV, the required CTV to PTV margins are smaller for the daily online soft tissue
      set-up compared with skin or bone.

PMID- 22858440
TI  - Low efficacy of noninvasive mechanical ventilation in respiratory failure after
      cardiac surgery: where is the mystery?

PMID- 22858442
TI  - Coexistence of pustular and vegetative pyoderma gangrenosum in a patient with
      myelodysplastic syndrome.

PMID- 22858443
TI  - Risk factors of viral hepatitis: yet to explore.
AB  - BACKGROUND AND AIMS: The safety of donated blood is the most vital concern of a
      blood transfusion organization. Hepatitis B virus (HBV), hepatitis C virus (HCV),
      and human immunodeficiency virus (HIV) screening for blood transfusion products
      has gained more importance where knowing the prevalence rate will help health
      policy makers. In this paper, we will evaluate the prevalence of viral infection
      in donated blood in the province of Qazvin in 2009. MATERIALS AND METHODS: This
      study has been conducted using a registration system of computerized records for
      donors in Qazvin in 2009 using the consensus mode on 20,591 blood donors. The
      results of their HBV, HCV, and HIV viral markers were evaluated and analyzed
      using the chi square statistical test. RESULTS: The prevalence rate of HBV, HCV,
      and HIV viral markers using the ELISA primary test in the individuals studied has
      been 0.28%, 1.59% and 0.1%, respectively, and on the basis of their confirmatory
      tests, 0.23%, 0.17% and 0%, respectively. There was no significant statistical
      difference in their infection rate on the basis of sex and marital status.
      Regular donors (46.85%) had a smaller infection rate compared to others
      (P<0.005). There was a significant statistical difference in the rate of
      prevalence of infection for hepatitis B and C in the regular donors compared to
      first-time donors. CONCLUSION: Considering the lower prevalence of viral markers
      in regular donors it is recommended that more use be made of them for blood
      donation.

PMID- 22858444
TI  - Is there any relationship between expressions of minor blood group antigens with
      HTLV-I infection?
AB  - BACKGROUND: The frequency of Human T lymphotropic Virus-1 (HTLV 1) is 2-3% in the
      general population and 0.7% in blood donors in northeast Iran. It is very
      important that we recognize the contributing factors in the pathogenesis of this
      virus. There are many reports that show that susceptibility to some infections is
      closely linked to the expression of certain blood group antigens. This study was
      performed to evaluate any association between minor blood group antigens and HTLV
      I infection in northeast Iran. METHODS: In this case and control study major and
      minor blood group antigens were typed by commercial antibodies in 100 HTLV-I
      infected individuals and 332 healthy blood donors in Mashhad, Iran, from 2009
      2010. Blood group antigens were determined by tube method less than 24h after
      blood collection. Finally, the results of HTLV-I positive subjects and control
      groups were compared by using SPSS software. RESULTS: The prevalence of Le(a),
      Le(b), P1, Fy(a), Fy(b), M, N, Jka, Jkb, K and k antigens in case group were
      39.0%, 56.0%, 72.0%, 67.0%, 52.0%, 90.0%, 57.0%, 79.0%, 71.0%, 10.0%, 96.0%,
      respectively and the frequency of these blood group antigens in control group
      were 38.8%, 55.8%, 66.2%, 72.0%, 58.7%, 87.0%, 56.7%, 79.8%, 63.0%, 10.6%, 97.0%,
      respectively. We did not find any significant differences between the case and
      control group for frequency of minor blood group antigens. CONCLUSION: Our study
      showed minor blood group antigens are not associated with an increased risk of
      HTLT-1 infection in northeast Iran.

PMID- 22858446
TI  - Resistance profiles and rpoB gene mutations of Mycobacterium tuberculosis
      isolates in Taiwan.
AB  - BACKGROUND/PURPOSE: The rifampicin resistance of Mycobacterium tuberculosis is
      caused by mutations in the 81-base pair region of the rpoB gene encoding the beta
      subunit of RNA polymerase. Sequences of the rpoB gene of 68 isolates were
      analyzed to identify the mutations and to compare the mutations with their
      related susceptibilities. METHODS: Susceptibility tests of 68 M. tuberculosis
      isolates, collected in Taiwan during the period from 1999 to 2011, were performed
      by the modified agar proportion method according to Clinical and Laboratory
      Standards Institute recommendations. Sequences of the rpoB gene and the
      resistance profiles were analyzed and compared with the data from different
      geographic regions. RESULTS: Seven alleles were identified. Among 47 isolates of
      allele 1 (without mutations of rpoB), 46 were rifampicin-susceptible. The other
      21 isolates (alleles 2 to 7, with mutations of rpoB) were rifampicin-resistant,
      including 18 isolates that were multidrug-resistant. Five mutated alleles
      demonstrated a single mutation. The mutations occurred in the codons 531 (68.2%),
      513 (9.1%), 533 (9.1%), 516 (4.5%), and 526 (4.5%). The sensitivity and
      specificity of rpoB mutations for predicting the rifampicin-resistance of M.
      tuberculosis were 95.5% and 100%, respectively. CONCLUSION: The most prevalent
      mutations of the rpoB gene were missense mutations in the critical codons,
      encoding Ser-531, Gln-513, Leu-533, Asp-516, and His-526. These mutations had
      high sensitivity and specificity for predicting the rifampicin-resistance of M.
      tuberculosis isolates. The resistance profiles and the frequencies of mutated
      codons of the rpoB gene varied in different geographic regions, indicating that
      resistance evolved under the selective pressure of the therapeutic regimens and
      the spread of different genetic clones.

PMID- 22858447
TI  - Influence of the timing of tumor regression after the initiation of
      chemoradiotherapy on prognosis in patients with limited-disease small-cell lung
      cancer achieving objective response.
AB  - PURPOSE: Chemoradiotherapy (CHRT) yields a favorable antitumor activity in
      patients with limited-stage small-cell lung cancer (LD-SCLC) with a response rate
      of around 80%. Even in such responders, the majority recur, indicating the
      importance of identifying a subset of patients with a poor outcome earlier
      through the treatment. We investigated whether the timing of obtaining tumor
      regression with the CHRT could affect the prognosis in LD-SCLC patients who
      finally achieved the objective response through the treatment. PATIENTS AND
      METHODS: We retrospectively reviewed medical charts of 70 LD-SCLC patients who
      obtained complete response (CR) or partial response (PR) with the 3 or 4 cycles
      of first-line CHRT between 1988 and 2006. RESULTS: In the whole 70 patients with
      CR/PR, the median survival time and median progression free survival (PFS) were
      39.6 and 12.3months, respectively. Fifty-two (74.3%) of the 70 patients entered
      CR/PR after the first cycle of CHRT, and their 2-year survival rates were
      significantly longer than that in the remaining 18 patients without entering
      CR/PR yet at the end of first cycle (72.3% and 7.1%, respectively, p<0.001). Cox
      regression analysis showed that the early response to the treatment was a
      significant prognostic factors (hazard ratio=0.098; 95% confidence interval=0.036
      0.269). Regarding PFS, similar findings were observed. CONCLUSIONS: Patients
      without entering CR/PR yet after the first course had a poorer outcome even
      though the objective response was finally confirmed through the treatment.
      Development of more effective treatments for these high-risk patients is
      warranted to improve their poor prognosis.

PMID- 22858445
TI  - Acute effects of prostaglandin E1 and E2 on vascular reactivity and blood flow in
      situ in the chick chorioallantoic membrane.
AB  - The chick chorioallantoic membrane (CAM) subserves gas exchange in the developing
      embryo and shell-less culture affords a unique opportunity for direct
      observations over time of individual blood vessels to pharmacologic
      interventions. We tested a number of lipids including prostaglandins PGE(1&2) for
      vascular effects and signaling in the CAM. Application of PGE(1&2) induced a
      decrease in the diameter of large blood vessels and a concentration-dependent,
      localized, reversible loss of blood flow through small vessels. The loss of flow
      was also mimicked by misoprostol, an agonist for 3 of 4 known PGE receptors, EP(2
      4), and by U46619, a thromboxane mimetic. Selective receptor antagonists for
      EP(3) and thromboxane each partially blocked the response. This is a first report
      of the effects of prostaglandins on vasoreactivity in the CAM. Our model allows
      the unique ability to examine simultaneous responses of large and small vessels
      in real time and in vivo.

PMID- 22858448
TI  - A diagnostic algorithm using EGFR mutation-specific antibodies for rapid response
      EGFR-TKI treatment in patients with non-small cell lung cancer.
AB  - BACKGROUND: We previously reported that EGFR mutation-specific antibodies
      performed well in immunohisto/cytochemical analysis. Assessment of EGFR mutation
      status for EGFR-TKIs (tyrosin kinase inhibitors) treatment of non-small cell lung
      cancer (NSCLC) patients can be performed by DNA-based assay. To establish a
      testing algorithm for EGFR mutation status in NSCLC patients, we utilized the
      peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay to determine
      the EGFR mutation, and immunostaining to detect the delE746-A750 and L858R
      mutation protein. PATIENTS AND METHODS: One hundred thirty-three patients with
      NSCLC were examined by immunostaining with EGFR mutation-specific antibodies, and
      by the PNA-LNA PCR clamp assay, using histological or cytological samples. The
      expression levels of immunostaining were classified as positive (score 2+),
      negative (score 0) or equivocal (score 1+), indicating questionable, negative or
      weak expression. Of these patients, 42 NSCLC patients received EGFR-TKIs
      treatment and we analyzed whether expression of mutant EGFR proteins was
      correlated with progression-free survival in patients with NSCLC treated with
      EGFR-TKIs. RESULTS: In the 133 samples, positive, negative and equivocal results
      for EGFR mutation-specific antibodies were observed in 37 patients (27.8%), 85
      patients (63.9%) and 11 patients (8.3%), respectively. Thirty-seven patients
      showed positive EGFR expression by immunostaining, and 35 (94.6%) of these also
      tested positive in the DNA-based assay. Of 85 EGFR-negative patients by
      immunostaining, 77 (90.6%) also tested negative in the DNA-based assay. Of the 11
      patients with equivocal immunostaining results, DNA-based assay detected EGFR
      mutation in 8 (72.7%) patients. Immunostaining for the EGFR mutation-specific
      antibodies showed a sensitivity of 81.4%, specificity of 97.5%, positive
      predictive value of 94.6% and negative predictive value of 90.6%, excluding the
      11 patients with equivocal results. In NSCLC patients treated with EGFR-TKIs, the
      progression-free survival after the start of EGFR-TKIs treatment was
      significantly longer in patients with EGFR positive expression than in those with
      equivocal and negative expression (P=0.002). CONCLUSIONS: Our results suggest
      that patients testing positive for EGFR mutations by immunostaining are good
      candidates for rapid response EGFR-TKI therapy. Immunostaining for EGFR mutation
      specific antibodies is a new test for EGFR-TKI inhibition and could be a useful
      indicator with regard to patient management.

PMID- 22858449
TI  - Acute effects of electronic and tobacco cigarette smoking on complete blood
      count.
AB  - The World Health Organisation called for research assessing the safety of
      electronic cigarette (e-cigarette). We evaluated the acute effect of active and
      passive e-cigarette and tobacco cigarette smoking on complete blood count (CBC)
      markers in 15 smokers and 15 never-smokers, respectively. Smokers underwent a
      control session, an active tobacco cigarette smoking session, and an active e
      cigarette smoking session. Never-smokers underwent a control session, a passive
      tobacco cigarette smoking session, and a passive e-cigarette smoking session. The
      results demonstrated that CBC indices remained unchanged during the control
      session and the active and passive e-cigarette smoking sessions (P>0.05). Active
      and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and
      granulocyte counts for at least one hour in smokers and never smokers (P<0.05).
      It is concluded that acute active and passive smoking using the e-cigarettes
      tested in the current study does not influence CBC indices in smokers and never
      smokers, respectively. In contrast, acute active and passive tobacco cigarette
      smoking increase the secondary proteins of acute inflammatory load for at least
      one hour. More research is needed to evaluate chemical safety issues and other
      areas of consumer product safety of e-cigarettes, because the nicotine content in
      the liquids used may vary considerably.

PMID- 22858451
TI  - Factors influencing discrepancies between the QuantiFERON-TB gold in tube test
      and the tuberculin skin test in Korean patients with rheumatic diseases.
AB  - OBJECTIVES: To estimate the positivity and agreement between QuantiFERON
      tuberculosis (TB) gold in tube test (QFT-GIT) and tuberculin skin test (TST)
      according to underlying rheumatic diseases and to identify the influencing
      factors on discrepancies between the 2 tests. METHODS: Among the 757 patients who
      underwent both QFT-GIT and TST simultaneously from September 2008 to November
      2010, patients with indeterminate QFT-GIT results (n = 21), with active (n = 11)
      or suspicious (n = 1) findings for tuberculosis on a chest radiograph, were
      excluded. Finally, 724 patients were recruited for this study: 497 patients with
      rheumatoid arthritis (RA), 198 with ankylosing spondylitis (AS), and 29 with
      juvenile rheumatoid arthritis (JRA). The agreement between the 2 tests was
      estimated by Cohen's kappa and factors influencing discrepancies were identified
      using multivariate analysis. RESULTS: The positivity of QFT-GIT was higher in RA
      than AS or JRA (30.2%, 16.2%, and 3.4%, respectively). In contrast, TST
      positivity was highest in AS compared to RA and JRA (45.5%, 28.2%, and 17.2%,
      respectively). The agreement between the 2 tests was low in all patients (kappa =
      0.285). The only predictor of a discrepancy between the 2 tests was older age.
      Factors associated with discordant QFT-GIT-negative/TST-positive results were
      female [odds ratio (OR) = 2.33, confidence interval (CI) 1.11 to 4.89] and AS (OR
      = 3.12, CI 1.44 to 6.79), whereas a discordant QFT-GIT-positive/TST-negative
      result was associated with glucocorticoid use (OR = 2.44, CI 1.24 to 4.81).
      CONCLUSIONS: The agreement between the 2 tests is low; therefore, it would be
      better to perform both tests than to use any 1 test alone for the detection of
      LTBI in TB-endemic regions. Female and underlying AS are related to being QFT-GIT
      negative/TST-positive, and the use of glucocorticoid is associated with being QFT
      GIT-positive/TST-negative.

PMID- 22858450
TI  - Corynebacterium aquatimens sp. nov., a lipophilic Corynebacterium isolated from
      blood cultures of a patient with bacteremia.
AB  - An unknown lipophilic coryneform bacterium isolated from the blood cultures of a
      patient with bacteremia was characterized by phenotypic and molecular genetic
      methods. Chemical analysis revealed the presence of short chain mycolic acids
      consistent with the genus Corynebacterium. The DNA G+C content was 60.8 mol%.
      Comparative 16S rRNA gene sequence analysis demonstrated that the isolate
      represents a new subline within the genus Corynebacterium. The closely
      phylogenetic relative of the unknown bacterium was found to be C. tuscaniense
      (97.8% sequence similarity). Partial rpoB gene sequence revealed that strain
      IMMIB L-2475(T) exhibited 13.5% sequence divergence with C. tuscaniense. The
      unknown bacterium was distinguished from C. tuscaniense by, DNA-DNA
      hybridization, cellular fatty acid profiles, MALDI-TOF analyses of cell extracts
      and biochemical tests. Based on the phylogenetic and phenotypic criteria, it is
      proposed that this bacterium be classified as new species, Corynebacterium
      aquatimens sp. nov., and is represented by strain IMMIB L-2475(T) (=DSM
      45632(T)=CCUG 61574(T)).

PMID- 22858452
TI  - Comparison of conventional and low dose steroid in the treatment of PFAPA
      syndrome: preliminary study.
AB  - BACKGROUND: Steroids have been widely used to relief symptoms in the patients
      with PFAPA syndrome. OBJECTIVES: This study was constructed to show the
      effectiveness of low-dose steroid therapy in patients diagnosed with PFAPA
      syndrome. METHODS: 41 patients (86 febrile attacks) who were diagnosed using the
      criteria suggested by Thomas et al. were involved in the study. The cases were
      classified into two groups and the selection of patients in groups was made
      randomly. Twenty patients received prednisolone at a dose of 2 mg/kg/day (first
      group: 40 attacks) and 21 patients received a dose of 0.5 mg/kg/day (second
      group: 46 attacks). The effectiveness of the treatment was especially determined
      by the time needed to reduce the fever and the effect on the duration between the
      two attacks. The patients were re-examined 24 hours later, after a steroid
      treatment. RESULTS: The patients who were in the first group received 2mg/kg/day
      dose of prednisolone and their fever was dramatically decreased in 6-8 hours (7.6
      +/- 0.9 hours). The second group received 0.5mg/kg/day dose and 19 of these
      patients' fever was decreased in 8-12 hours. Two patients whose temperature did
      not decrease, received another dose of prednisolone 24 hours after the first dose
      and their fever was reduced 12 hours after the second dose (11.3 +/- 6.4 hours).
      A comparison of the rate of fever reduction and the interval between the attacks
      (Group I: 5.11 +/- 1.01 week and Group II: 5.2 +/- 1.13 week) in the two groups
      did not show any statistical significance (p=0.104). CONCLUSION: Low-dose steroid
      treatment is as effective as normal dose in PFAPA syndrome but there is need to
      study with a larger group.

PMID- 22858453
TI  - Outcomes of HeartWare Ventricular Assist System support in 141 patients: a single
      centre experience.
AB  - OBJECTIVES: A third-generation ventricular assist device, the HeartWare
      Ventricular Assist System, has demonstrated its reliability and durability in
      animal models and clinical experience. However, studies of a large series of
      applications are still lacking. We evaluate the safety and efficacy of the
      HeartWare pump in 141 patients with end-stage heart failure at a single centre.
      METHODS: A total of 141 patients (116 men and 25 women with a mean age of 52
      years) in New York Heart Association (NYHA) Class IV received implantation of the
      HeartWare Ventricular Assist System between August 2009 and April 2011 at the
      Deutsches Herzzentrum Berlin. The outcomes were measured in terms of laboratory
      data, adverse events, NYHA functional class and survival during device support.
      RESULTS: The HeartWare system provided an adequate haemodynamic support for
      patients both inside and outside the hospital. NYHA class improved to I-II. Organ
      function and pulmonary vascular resistance improved significantly. In this cohort
      of patients, 14 patients underwent heart transplantation, one had had the device
      explanted following myocardial recovery, one had changed to another assist
      device, 81 were on ongoing support and 44 died. The overall actuarial survival
      rates at 6 and 12 months were 70 and 67%, respectively, and the 3-, 6- and 12
      month survival rates on a left ventricular assist device (LVAD) support for
      bridge to transplantation patients were 82, 81 and 79%, respectively. Infection
      and bleeding were the main adverse events. Four patients underwent an LVAD
      exchange for pump thrombosis. CONCLUSIONS: The HeartWare system provides a safe
      and effective circulatory support in a population with a wide range of body
      surface areas, with a satisfactory actuarial survival time and an improved
      quality of life. It can be used for univentricular or biventricular support,
      being implanted into the pericardial space with simplified surgical techniques.

PMID- 22858454
TI  - How to identify active novel agents in rare cancers and then make them available:
      a need for a paradigm shift.

PMID- 22858455
TI  - Technical advances in bladder cancer patient care: progress or promise?

PMID- 22858456
TI  - Re: Fritz H. Schroder, Jonas Hugosson, Sigrid Carlsson, et al. Screening for
      prostate cancer decreases the risk of developing metastatic disease: findings
      from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur
      urol 2012;62:745-52.

PMID- 22858457
TI  - Towards the ideal partial nephrectomy.

PMID- 22858458
TI  - Correction.

PMID- 22858459
TI  - Reductions in hospital admissions and mortality rates observed after integrating
      emergency care: a natural experiment.
AB  - OBJECTIVES: Reducing emergency admissions is a priority for the NHS. A single
      hospital's emergency care system was reorganised with the principles of front
      loaded investigations, integration of specialties, reduced duplication, earlier
      decision making by senior clinicians and a combined emergency assessment area.
      The authors relocated our Medical Assessment Unit into our emergency department
      in 2006. The authors evaluated changes in admissions and mortality before and
      after 2006, compared with other similar hospitals. DESIGN: Quasi-experimental
      before and after study using routinely collected data. SETTING AND PARTICIPANTS:
      1 acute hospital in England, the intervention site, was compared with 23 other
      English hospitals between 2001 and 2009. OUTCOME MEASURES: Our outcome measures
      were hospital standardised mortality ratios (HSMRs) for non-elective admissions
      and standardised admission ratios (SARs). RESULTS: The authors observed a
      statistically and clinically significant decrease in HSMR and SAR. The
      intervention hospital had the lowest HSMR and SAR of all the hospitals in our
      sample. This was statistically significant, p=0.0149 and p=0.0002, respectively.
      CONCLUSION: Integrating emergency care in one location is associated with a
      meaningful reduction in mortality and emergency admissions to hospital.

PMID- 22858460
TI  - Screening of emerging contaminants and priority substances (2008/105/EC) in
      reclaimed water for irrigation and groundwater in a volcanic aquifer (Gran
      Canaria, Canary Islands, Spain).
AB  - In semiarid regions, reclaimed water can be an important source of emerging
      pollutants in groundwater. In Gran Canaria Island, reclaimed water irrigation has
      been practiced for over thirty years and currently represents 8% of water
      resources. The aim of this study was to monitor contaminants of emerging concern
      and priority substances (2008/105/EC) in a volcanic aquifer in the NE of Gran
      Canaria where the Bandama Golf Course has been sprinkled with reclaimed water
      since 1976. Reclaimed water and groundwater were monitoring quarterly from July
      2009 to May 2010. Only 43% of the 183 pollutants analysed were detected: 42
      pharmaceuticals, 20 pesticides, 12 polyaromatic hydrocarbons, 2 volatile organic
      compounds and 2 flame retardants. The most frequent compounds were caffeine,
      nicotine, chlorpyrifos ethyl, fluorene, phenanthrene and pyrene. Concentrations
      were always below 50 ng L(-1), although some pharmaceuticals and one pesticide,
      cholrpyrifos ethyl, were occasionally detected at higher concentrations. This
      priority substance for surface water exceeded the maximum threshold (0.1 MUg L(
      1)) for pesticide concentration in groundwater (2006/118/EC). Sorption and
      degradation processes in soil account for more compounds being detected in
      reclaimed water than in groundwater, and that some contaminants were always
      detected in reclaimed water, but never in groundwater (flufenamic acid,
      propyphenazone, terbutryn and diazinon). Furthermore, erythromycin was always
      detected in reclaimed water (exceeding occasionally 0.1 MUg L(-1)), and was
      detected only once in groundwater. In contrast, some compounds (phenylephrine,
      nifuroxazide and miconazole) never detected in reclaimed water, were always
      detected in groundwater. This fact and the same concentration range detected for
      the groups, regardless of the water origin, indicated alternative contaminant
      sources (septic tanks, agricultural practices and sewerage breaks). The
      widespread detection of high adsorption potential compounds, and the independence
      of concentration with origin and depths, indicates the existence of preferential
      flows phenomena as potential contamination route in volcanic fractured materials.

PMID- 22858461
TI  - Xylans inhibit enzymatic hydrolysis of lignocellulosic materials by cellulases.
AB  - Hemicelluloses have been found to be physical barriers in the hydrolysis of
      cellulose, and prevent the access of enzymes to cellulose surface. In addition,
      soluble hemicelluloses may strongly inhibit the cellulase activity. In this work,
      birchwood xylan clearly inhibited the enzymatic hydrolysis of wheat straw, Avicel
      and nanocellulose by cellulases. Hydrolysis efficiencies of cellobiohydrolase I
      (CBHI, from Thermoascus aurantiacus), cellobiohydrolase II (CBHII, from
      Trichoderma reesei) and endoglucanase II (from T. aurantiacus) were clearly
      inhibited by birchwood xylan, respectively. The strongest inhibitory effect of
      birchwood xylan was observed on the hydrolysis of Avicel by CBHI and CBHII, as a
      dramatically decreased formation of the main product, cellobiose. After additions
      of soluble and insoluble oat spelt xylan, cleaved cellobiose units by CBHI from
      cellulose chain decreased from 8 to 4 and 6, respectively. The results in this
      work demonstrated that xylans clearly inhibited the hydrolysis efficiencies of
      both endoglucanase and cellobiohydrolase.

PMID- 22858462
TI  - New cost-effective method for conversion of vegetable oil to biodiesel.
AB  - A low cost method to convert triglycerides to biodiesel by transesterification
      reaction has been investigated. The new approach is based on controlled feeding
      of oil into a pool of alcohol allowing easy dispersion of oil creating large
      interfacial area for mass transfer. It also enabled equilibrium constants to
      shift in the forward direction due to excess of alcohol in the dispersion. As a
      result product yield higher than 95% could be achieved at lower energy input
      compared to conventional method. Comparisons made with conventional batch and co
      solvent enabled method show differences and highlight improvements. Reactions
      were conducted in one liter reactor at various residence time, temperature and
      molar ratio of canola oil with methanol in presence of potassium hydroxide as the
      catalyst. Samples were collected at regular intervals and analyzed by gas
      chromatography (GC) to determine the reaction progress.

PMID- 22858463
TI  - Effects of glucose on the performance of enhanced biological phosphorus removal
      activated sludge enriched with acetate.
AB  - The effects of glucose on enhanced biological phosphorus removal (EBPR) activated
      sludge enriched with acetate was investigated using sequencing batch reactors. A
      glucose/acetate mixture was serially added to the test reactor in ratios of
      25/75%, 50/50%, and 75/25% and the EBPR activity was compared to the control
      reactor fed with 100% acetate. P removal increased at a statistically significant
      level to a near-complete in the test reactor when the mixture increased to
      50/50%. However, EBPR deteriorated when the glucose/acetate mixture increased to
      75/25% in the test reactor and when the control reactor abruptly switched to 100%
      glucose. These results, in contrast to the EBPR conventional wisdom, suggest that
      the addition of glucose at moderate levels in wastewaters does not impede and may
      enhance EBPR, and that glucose waste products should be explored as an economical
      sustainable alternative when COD enhancement of EBPR is needed.

PMID- 22858464
TI  - Cadmium adsorption characteristic of alkali modified sewage sludge.
AB  - This paper proposed a new biosorbent preparation method by alkali modification of
      sewage sludge. The cadmium ion (Cd(2+)) adsorption capacity of alkali modified
      sewage sludge (AMSS) was evaluated by equilibrium sorption experiments. The
      amount of released calcium ion (Ca(2+)) in sorption equilibrium experiment were
      measured in order to reveal the adsorption mechanism. In addition, Zeta
      potential, specific surface area and Fourier transform infrared (FTIR) spectra of
      AMSS were tested. The results showed that the cadmium adsorption isotherms of
      AMSS fitted well with both Langmuir and Freundlich models, and the maximum
      adsorption capacities increased by 0.713 mmol g(-1). The cadmium adsorption
      capacity of biosorbent increased with NaOH solution concentration (range from
      0.25 to 7.5 mol L(-1)) for sewage sludge modification. The strong cadmium
      adsorption of AMSS was attributed to ion exchange effect, electrostatic
      attraction and complexation. This alkali modified sewage sludge may have a
      potential for serving as cadmium removal biosorbent.

PMID- 22858465
TI  - Antibiotic Fermentation Broth Treatment by a pilot upflow anaerobic sludge bed
      reactor and kinetic modeling.
AB  - In this study, an upflow anaerobic sludge blanket (UASB) mesophilic reactor was
      used to remove antibiotic fermentation broth wastewater. The hydraulic retention
      time was held constant at 13.3 days. The volumetric organic loading value
      increased from 0.33 to 7.43 kg(COD)m(-3)d(-1) using antibiotic fermentation broth
      wastewater gradually diluted with various ratios of domestic wastewater. A COD
      removal efficiency of 95.7% was obtained with a maximum yield of 3,700 L d(-1)
      methane gas production. The results of the study were interpreted using the
      modified Stover-Kincannon, first-order, substrate mass balance and Van der Meer
      and Heertjes kinetic models. The obtained kinetic coefficients showed that
      antibiotic fermentation broth wastewater can be successfully treated using a UASB
      reactor while taking COD removal and methane production into account.

PMID- 22858466
TI  - Simulation on gasification of forestry residues in fluidized beds by Eulerian
      Lagrangian approach.
AB  - A comprehensive three-dimensional numerical model is developed to simulate
      forestry residues gasification in a fluidized bed reactor using Eulerian
      Lagrangian approach. The complex granular flow behaviors and chemical reaction
      characteristics are addressed simultaneously. The model uses an Eulerian method
      for fluid phase and a discrete particle method for solid phase, which takes
      particle contact force into account. Heterogeneous and homogenous reaction rates
      are solved on the Eulerian grid. The numerical model is employed to study the
      gasification performance in a lab-scale pine gasifier. A series of simulations
      have been performed with some critical parameters including temperature,
      equivalence ratio and steam to biomass ratio. The model predicts product gas
      composition and carbon conversion efficiency in good agreement with experimental
      data. The formation and development of flow regimes, profiles of particle
      species, and distributions of gas compositions inside the reactor are also
      discussed.

PMID- 22858467
TI  - Non-ionic polysorbate surfactants: alternative inducers of medium-chain-length
      poly(3-hydroxyalkanoates) (MCL-PHAs) for production of extracellular MCL-PHA
      depolymerases.
AB  - The potential of non-ionic polysorbate surfactants as alternative inducers of
      medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) for the production of
      diverse bacterial MCL-PHA depolymerases was evaluated. When grown with corn oil
      as the sole carbon substrate, Pseudomonas alcaligenes LB19 preferentially
      produced lipolytic enzymes, but its MCL-PHA depolymerase was not induced by the
      substrate. However, the results of activity staining and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis clearly revealed that Tween 20
      induced simultaneous production of lipolytic enzymes and the MCL-PHA depolymerase
      with the molecular mass (26.5 kDa) of P. alcaligenes LB19, which has been
      previously identified. Moreover, the co-production of two functionally distinct
      hydrolytic enzymes induced by Tween 20 was commonly observed in various Gram
      positive and Gram-negative bacteria that were fed the substrate. Thus, it is
      expected that non-ionic polysorbate surfactants including Tween 20 can be widely
      exploited as promising universal substrates for the facile and efficient
      production of diverse MCL-PHA depolymerases.

PMID- 22858468
TI  - Characterization of the lipid accumulation in a tropical freshwater microalgae
      Chlorococcum sp.
AB  - A green microalgae strain, Chlorococcum sp. was obtained from tropical freshwater
      in Indonesia. The effects of pH on growth, effects of salt, carbon dioxide level,
      nitrate, acetate, and photoperiod on biomass and lipid production were studied.
      The fatty acids composition was also investigated. This study shows that the
      strain had an optimum pH value for growth ranging from pH 8.0 to 8.5. The biomass
      concentration and lipid content were influenced by different concentrations of
      salt, CO(2) and nitrate. The lipid productivity ranged from 2 to 90.8 mg L(-1)d(
      1) in different mediums. The highest biomass concentration and total lipid
      content achieved were 1.75 g L(-1) and 56% of dry weight, respectively. Moreover,
      the major fatty acid methyl esters were C16:0, C18:1, C18:2 and C18:3. The high
      lipid content and the fatty acid composition make the strain Chlorococcum sp. a
      potential resource for food, cosmetics and biodiesel.

PMID- 22858469
TI  - Cultivation of Chlorella zofingiensis in bench-scale outdoor ponds by regulation
      of pH using dairy wastewater in winter, South China.
AB  - Cultivation of Chlorella zofingiensis and nutrients removal in dairy wastewater
      were investigated in bench-scale outdoor ponds in winter, South China. The
      impacts of the two types of pH regulations, 5 ~ 6% CO(2) and acetic acid (HAc) on
      this process were studied. After 6 days cultivation, the removal rates of total
      nitrogen (TN) and orthophosphate (PO(4)(3-)) using CO(2) regulation were better
      than those using HAc. The removal rates of PO(4)(3-) and TN were 97.5% and 51.7%,
      respectively using CO(2) regulation; 79.6% (TN) and 42.0% (PO(4)(3-)) were
      obtained using HAc regulation. Higher biomass, protein, sugar content, and stable
      pH control were found using CO(2) regulation. However, significantly higher lipid
      content (31.8%) was observed using HAc regulation. The dominant differences of
      fatty acids were the content of C18:1 and C18:3. The growth characteristics and
      environmental conditions especially during the typical logarithmic phase were
      also analyzed.

PMID- 22858470
TI  - Bioproduction, statistical optimization and characterization of microbial plastic
      (poly 3-hydroxy butyrate) employing various hydrolysates of water hyacinth
      (Eichhornia crassipes) as sole carbon source.
AB  - Saccharified water hyacinth hydrolysates (acid and enzyme hydrolysate) were used
      for the efficient production of poly (3-hydroxybutyrate) (PHB) via the
      Cupriavidus necator bacteria. The bacterium significantly utilizes the enzymatic
      hydrolyzate which gave the maximum PHB concentration (4.3 +/- 0.4 g L(-1)), this
      was greatly exceeded the value of 2 +/- 0.1 g L(-1) obtained from the acid
      hydrolysate amended media. Moreover, for the optimal PHB production, response
      surface methodology was used through central composite rotary design method which
      gave improved PHB concentration in microbial cells. After 72 h, 35 g L(-1) of
      reducing sugar contained water hyacinth hydrolysate and 1.5 g L(-1) of
      (NH(4))(2)SO(4) supplementation in laboratory scale fermentor gave 12 g L(-1) of
      dry cell weight and 7 g L(-1) of PHB. The produced PHB was characterized under
      FTIR, GPC and DSC instruments to find out the number average molecular mass,
      polydispersity index and melting temperature were 1.7 * 10(5)kDa, 1.9 and 170
      degrees C respectively.

PMID- 22858471
TI  - Production of ethyl levulinate by direct conversion of wheat straw in ethanol
      media.
AB  - The production of ethyl levulinate from wheat straw by direct conversion in
      ethanol media was investigated. Response surface methodology (RSM) was applied to
      optimize the effects of processing parameters, and the regression analysis was
      performed on the data obtained. A close agreement between the experimental
      results and the model predictions was achieved. The optimal conditions for ethyl
      levulinate production from wheat straw were acid concentration 2.5%, reaction
      temperature 183 degrees C, mass ratio of liquid to solid 19.8 and reaction time
      36 min. Under the optimum conditions, the yield of ethyl levulinate 17.91% was
      obtained, representing a theoretical yield of 51.0%. The results suggest that
      wheat straw can be used as potential raw materials for the production of ethyl
      levulinate by direct conversion in ethanol media.

PMID- 22858472
TI  - Pretreatment based on two-step steam explosion combined with an intermediate
      separation of fiber cells--optimization of fermentation of corn straw
      hydrolysates.
AB  - Pretreatment is necessary for lignocellulose to achieve a highly efficient
      enzymatic hydrolysis and fermentation. However, coincident with pretreatment,
      compounds inhibiting microorganism growth are formed. Some tissues or cells, such
      as thin-walled cells that easily hydrolyze, will be excessively degraded because
      of the structural heterogeneity of lignocellulose, and some inhibitors will be
      generated under the same pretreatment conditions. Results showed, compared with
      one-step steam explosion (1.2 MPa/8 min), two-step steam explosion with an
      intermediate separation of fiber cells (ISFC) (1.1 Mpa/4 min-ISFC-1.2 MPa/4 min)
      can increase enzymatic hydrolyzation by 12.82%, reduce inhibitor conversion by
      33%, and increase fermentation product (2,3-butanediol) conversion by 209%. Thus,
      the two-step steam explosion with ISFC process is proposed to optimize the
      hydrolysis process of lignocellulose by modifying the raw material from the
      origin. This novel process reduces the inhibitor content, promotes the
      biotransformation of lignocellulose, and simplifies the process of excluding the
      detoxification unit operation.

PMID- 22858473
TI  - L-lactic acid production by Bacillus subtilis MUR1.
AB  - Bacillus subtilis MUR1 is a novel lactic acid (LA) producing strain that has the
      potential for industrial production of LA due to its high productivity of LA,
      high yield of substrate conversion, and high final concentration of LA produced.
      B. subtilis MUR1 can produce 99.3 and 183.2g/l of L-LA in 12 and 52 h
      respectively with a 98.5% substrate conversion yield and a maximum L-LA
      production rate of 16.1g/l/h. Compared with batch culture, and several fed-batch
      cultures with different initial glucose concentrations, the fed-batch culture
      with initial 30 g/l glucose produced the highest final concentration and
      productivity of L-LA. Corn steep liquor can be used to partly replace yeast
      extract in the production medium for the production of L-LA by B. subtilis MUR1.

PMID- 22858474
TI  - Stable aerobic granules in continuous-flow bioreactor with self-forming dynamic
      membrane.
AB  - A novel continuous-flow bioreactor with aerobic granular sludge and self-forming
      dynamic membrane (CGSFDMBR) was developed for efficient wastewater treatment.
      Under continuous-flow operation, aerobic granular sludge was successfully
      cultivated and characterized with small particle size of about 0.1-1.0mm, low
      settling velocity of about 15-25 m/h, loose structure and high water content of
      about 96-98%. To maintain the stability of aerobic granular sludge, strategies
      based on the differences of settling velocity and particle-size between granular
      and flocculent sludge were implemented. Moreover, in CGSFDMBR, membrane fouling
      was greatly relieved. Dynamic membrane was just cleaned once in more than 45
      days' operation. CGSFDMBR presented good performance in treating septic tank
      wastewater, obtaining average COD, NH(4)(+)-N, TN and TP removal rates of 83.3%,
      73.3%, 67.3% and 60%, respectively, which was more efficient than conventional
      bioreactors since that carbon, nitrogen and phosphorus were simultaneously
      removed in a single aerobic reactor.

PMID- 22858475
TI  - Comparative analysis of the bacterial diversity in a lab-scale moving bed biofilm
      reactor (MBBR) applied to treat urban wastewater under different operational
      conditions.
AB  - Different types of carriers were tested as support material in a lab-scale moving
      bed biofilm reactor (MBBR) used to treat urban wastewater under three different
      conditions of hydraulic retention time (HRT) and carrier filling ratios (FR). The
      bacterial diversity developed on the biofilms responsible of the treatment was
      studied using a cultivation-independent approach based on the polymerase chain
      reaction-temperature gradient gel electrophoresis technique (PCR-TGGE). Cluster
      analysis of TGGE fingerprints showed significant differences of community
      structure dependent upon the different operational conditions applied. Redundancy
      analysis (RDA) was used to determine the relationship between the operational
      conditions (type of carrier, HRT, FR) and bacterial biofilm diversity,
      demonstrating a significant effect of FR=50%. Phylogenetic analysis of PCR
      reamplified and sequenced TGGE bands revealed that the prevalent Bacteria
      populations in the biofilm were related to Betaproteobacteria (46%), Firmicutes
      (34%),Alphaproteobacteria (14%) and Gammaproteobacteria (9%).

PMID- 22858476
TI  - Addition of Bacillus sp. inoculums in bedding for swine on a pilot scale: effect
      on microbial population and bedding temperature.
AB  - Thermal and microbiological characteristics of beddings for swine were compared
      according to their depth and of addition of inoculums. Bedding was added to boxes
      at 0.25 (25D) and 0.50 m (50D), with three treatments: control (no inoculums);
      T1, with 250 g of Bacillus cereus var. toyoii at 8.4 * 10(7) CFU; and T2, with
      250 g of a pool of B. subtilis, Bacillus licheniformis and Bacillus polymyxa at
      8.4 * 10(7) CFU (250 g for 25D and 500 g for 50D). Mean temperatures were 28.5 +/
      3.9 at the surface and 35.2 +/- 8.9 inside the beddings. The most probable
      number (MPN) of thermophilic bacteria was higher for T1 and T2 than for the
      control (P<0.05). The MPN of thermophilic bacteria and fungi was greater for D50
      than for D25 (P<0.05). The use of 25D without inoculums is recommended due to the
      reduction of thermophilic microbiota.

PMID- 22858477
TI  - Enzymatic polymerisation and effect of fractionation of dissolved lignin from
      Eucalyptus globulus Kraft liquor.
AB  - The potential ability of the laccase from Myceliophthora thermophila, either
      alone or with low molecular weight (LMW) additives, to polymerise a dissolved
      lignin from Kraft liquor of eucalypt cooking was investigated. A previous study
      of enzymatic performance (activity and stability) was carried out using a design
      experiment methodology. In addition, Kraft dissolved lignin (KDL) was
      fractionated according to two different protocols (solvent extraction and acidic
      fractionation) in order to identify possible lignin fractions with noticeable
      polymerisation ability. KDL and its corresponding lignin fractions were treated
      with laccase and analysed by size exclusion chromatography and Fourier transform
      infrared spectroscopy. The results provide conclusive evidence of notable lignin
      modifications after incubation with laccase. Moreover, lignin fractionation
      allows to obtain lignin fractions with different chemical characteristics and
      polymerisation capability. Depending on the type of raw lignin, molecular weight
      can increase from 4- to 21-fold by means of laccase polymerisation.

PMID- 22858478
TI  - Supercritical water gasification of biomass for H2 production: process design.
AB  - The supercritical water gasification (SCWG) of biomass for H(2) production is
      analyzed in terms of process development and energetic self-sustainability. The
      conceptual design of a plant is proposed and the SCWG process involving several
      substrates (glycerol, microalgae, sewage sludge, grape marc, phenol) is simulated
      by means of AspenPlusTM. The influence of various parameters - biomass
      concentration and typology, reaction pressure and temperature - is analyzed. The
      process accounts for the possibility of exploiting the mechanical energy of
      compressed syngas (later burned to sustain the SCWG reaction) through expansion
      in turbines, while purified H(2) is fed to fuel cells. Results show that the SCWG
      reaction can be energetically self-sustained if minimum feed biomass
      concentrations of 15-25% are adopted. Interestingly, the H(2) yields are found to
      be maximal at similar feed concentrations. Finally, an energy balance is
      performed showing that the whole process could provide a net power of about 150
      kW(e)/(1000 kg(feed)/h).

PMID- 22858479
TI  - Enhanced azo dye wastewater treatment in a two-stage anaerobic system with Fe0
      dosing.
AB  - Azo dye wastewater treatment was enhanced in an acidogenic reactor (A1) by Fe(0)
      dosing. Both COD (50%) and color (60%) removal in A1 were stable when the dye
      concentrations were increased from 200 to 800 mg/L. However, the performances of
      a Fe(0)-free control reactor (A2) showed low COD (34%) and color (32%) removals.
      The reason was attributed that Fe(0) dosing enhanced the activity of fermentative
      bacteria, which played an important role in acidogenesis and decolorization. The
      methanogenic reactor fed with the effluent of A1 exhibited higher removal
      efficiency and treatment stability. These results suggested that Fe(0) powder
      dosing was helpful to improve acidogenesis and decolorization to create a
      favorable feeding condition for the subsequent methanogenic treatment.

PMID- 22858480
TI  - Characteristics of enzyme hydrolysis of cellulose under static condition.
AB  - The effect of enzyme loading under static and agitated conditions was
      investigated. Enzymatic hydrolysis of 10 w/v% de-lignified cellulose slurry such
      as filter paper, avicel and pulp was conducted under agitated (120 rpm) and
      static condition, and the enzyme loading ranging from 1.2 to 120 mg-protein/g-dry
      substrate. Under the agitated condition, the final sugar concentration decreased
      with the decreasing enzyme loading. Under the static condition, the final sugar
      concentration was maintained even if the enzyme loading was decreased. The above
      phenomenon was caused by a rapid precipitation of cellobiohydrolase 2 (CBH2)
      under the agitated condition, which was not observed under the static condition.
      The hydrolysis experiments using enzymes containing different ratios of
      cellobiohydrolase 1 (CBH1) and CBH2 under the static condition suggested that
      preservation of CBH2 and its synergism with CBH1 is essential for static
      condition's characteristics, and for efficient hydrolysis of cellulose.

PMID- 22858481
TI  - An integrated approach to optimize the conditioning chemicals for enhanced sludge
      conditioning in a pilot-scale sludge dewatering process.
AB  - An integrated approach incorporating response surface methodology (RSM), grey
      relational analysis, and fuzzy logic analysis was developed to quantitatively
      evaluate the conditioning chemicals in sludge dewatering process. The
      polyacrylamide (PAM), ferric chloride (FeCl(3)) and calcium-based mineral powders
      were combined to be used as the sludge conditioners in a pilot-scale sludge
      dewatering process. The performance of conditioners at varied dosages was
      comprehensively evaluated by taking into consideration the sludge dewatering
      efficiency and chemical cost of conditioner. In the evaluation procedure, RSM was
      employed to design the experiment and to optimize the dosage of each conditioner.
      The grey-fuzzy logic was established to quantify the conditioning performance on
      the basis of grey relational coefficient generation, membership function
      construction, and fuzzy rule description. Based on the evaluation results, the
      optimal chemical composition for conditioning was determined as PAM at 4.62 g/kg
      DS, FeCl(3) at 55.4 g/kg DS, and mineral powders at 30.0 g/kg DS.

PMID- 22858482
TI  - Quantitative evaluation of heavy metals in solid residues from sub- and super
      critical water gasification of sewage sludge.
AB  - Solid residues (SRs) are important byproducts of sub- and super-critical water
      gasification of sewage sludge (SS). In this study, the quantitative evaluation of
      heavy metals (HMs) in SRs, compared with SS, is applied in terms of potential
      ecological risks, pollution levels, and both bioavailability and eco-toxicity.
      The results show the bioavailability and eco-toxicity of HMs in SRs decrease,
      although the total concentration of HMs increased, particularly in the
      bioavailable fraction of Cu, which decreased nearly 97%. The geo-accumulation and
      potential ecological risk index indicated that the gasification process increased
      contamination by two levels (to the maximum), while the overall risk was in
      keeping with SS. However, based on the risk assessment code, each tested HM
      exhibited lower environmental risk after gasification, especially for Cd, which
      drastically dropped from 66.67 (very high risk) in SS to 0.71 (no risk) in SRs,
      with a reaction temperature of 375 degrees C for 60 min.

PMID- 22858483
TI  - Performance analysis of a combined system of membrane bioreactor and worm
      reactor: wastewater treatment, sludge reduction and membrane fouling.
AB  - A new process that combined a membrane bioreactor (S-MBR) and a novel worm
      reactor was proposed in this study. The combined system indicated excellent
      sludge reduction efficiency, wastewater treatment performance and membrane
      permeability. The sludge reduction percentage of the combined system was about
      1.9 times higher than that of the conventional MBR. The chemical oxygen demand
      (COD) discharge rate in the combined system was only one fourth of that in the
      conventional MBR, indicating that the COD was removed more thoroughly. Low
      extracellular polymeric substances level (60-75 MUg/mg), low filamentous bacteria
      level, narrow floc size distribution (distribution spread index of 0.91) and high
      roundness (0.80 +/- 0.10) were observed in the S-MBR sludge. Deposited by this
      modified sludge, a fouling layer with smaller thickness, larger porosity and less
      proteins and polysaccharides accumulation was formed in the S-MBR, demonstrating
      that the combined system was able to alleviate membrane fouling.

PMID- 22858484
TI  - Nutrient removal and phosphorus recovery performances of a novel anaerobic
      anoxic/nitrifying/induced crystallization process.
AB  - An anaerobic-anoxic/nitrifying (A(2)N) two sludge process coupled with induced
      crystallization (IC) called A(2)N-IC process was developed for wastewater
      nutrient removal and phosphorus recovery. The performances of A(2)N-IC process in
      comparison with A(2)N process at different COD to phosphorus (COD/P) feeding
      ratios were investigated. The results indicated that A(2)N-IC achieved not only
      high and stable nutrient removal but also phosphorus recovery. Calcium phosphorus
      crystals were formed in the crystallization reactor in A(2)N-IC. Moreover, the
      incorporation of chemical induced crystallization improved biological phosphorus
      removal. In A(2)N-IC process, phosphorus removal efficiency was consistently
      maintained at 99.2%, whereas in A(2)N it decreased from 93.0% to 65.7% with the
      decrease of feeding COD/P ratio. The COD and ammonia removal efficiencies were
      regardless of feeding COD/P ratio in the two processes.

PMID- 22858485
TI  - Does densification influence the steam pretreatment and enzymatic hydrolysis of
      softwoods to sugars?
AB  - The global trade in wood pellets continues to grow. However, their potential as a
      feedstock for large scale cellulosic ethanol production has not been evaluated.
      We anticipated that the reduced moisture content and pressure exerted on the wood
      biomass during the pelletisation process would result in some carbohydrate loss
      as well as making the biomass more recalcitrant to pretreatment and subsequent
      hydrolysis. However, when softwood chips and pellets were steam pretreated at
      medium severity, little hemicellulose loss occurred while more than two-thirds of
      the cellulose present in the cellulose rich water insoluble fractions were
      hydrolysed (at 20 FPU cellulase/g cellulose). In addition, prior steaming
      substantially reduced the particle size of the wood chips enabling direct
      pelletisation without the need for grinding. Surprisingly, it was also possible
      to apply a single steam pretreatment to facilitate both pelletisation and
      subsequent enzymatic hydrolysis without the need for a further pretreatment step.

PMID- 22858486
TI  - Tubular biofilter for toluene removal under various organic loading rates and gas
      empty bed residence times.
AB  - A tubular biofilter (TBF) which consisted of a closed chamber, a polyurethane
      sponge tube and a nutrient solution distributor was developed and evaluated under
      organic loading rates (OL) ranging from 18.7 to 149.3 gm(-3)h(-1) and gas empty
      bed residence times (EBRTs) of 30-5.0 s. Using toluene as model VOC, the startup
      of the TBF lasted approximately 7 weeks. The removal efficiency decreased from
      99% to 52.2% when OL was increased from 18.7 to 149.3g toluene m(-3)h(-1) at 15s,
      but did not decline significantly when the EBRT was reduced from 30 to 5.0 s at
      18.7 gm(-3)h(-1). Biomass concentration did not increase significantly within the
      sponge tube during the 391 days' operation as observed through the Plexiglas pipe
      of the TBF. The TBF is suitable for treating waste gases with low toluene
      concentrations even at high gas flow and over long periods.

PMID- 22858487
TI  - Comparative study of the use of pure oxygen and air in the nitrification of a MBR
      system used for wastewater treatment.
AB  - A MBR (membrane bioreactor) was performed to quantify the improvement in nitrogen
      removal terms when pure oxygen and air were used to supply the aerobic conditions
      at different HRT (hydraulic retention time) and mixed liquid suspended solids
      concentrations. The improvement in the efficiency was 8.0% and 13.5% when pure
      oxygen was used with 12h and 18 h of HRT respectively. The ammonium utilization
      rates with HRT of 18 h with pure oxygen was 1.23 mg N(t)/(L h) and with air 0.66
      mg N(t)/(L h) and with HRT of 12h was 1.14 mg N(t)/(L h) and 1.18 mg N(t)/(L h)
      respectively. Model simulation (DESSAS software) confirmed the validity for
      nitrogen removal, hydrolysis constant was increased (106% and 184%), decay
      constant was decreased and Monod's constant was increased (190.4% to 324.1%), and
      a multivariate analysis with CANOCO v4.5 demonstrated that temperature and HRT
      have the higher influence in kinetics.

PMID- 22858488
TI  - Chitosan hollow fibers as effective biosorbent toward dye: preparation and
      modeling.
AB  - Chitosan hollow fibers were produced via a dry-wet spinning technique with good
      mechanical properties. The prepared membranes were tested for removal of reactive
      blue 19 as a model anionic dye. Response surface methodology was employed for the
      modeling of adsorption capacity of fibers. A second-order empirical relationship
      between adsorption capacity and independent variables (initial pH, contact time,
      initial dye concentration and amount of fibers) was obtained. Pareto analysis
      established that initial pH was the most effective parameter. The adsorption
      capacity value of reactive blue 19 on chitosan hollow fibers was 454.5 mg g(-1).
      The adsorption was well described by pseudo-second-order kinetics and Freundlich
      equation.

PMID- 22858489
TI  - Influence of steam explosion on physicochemical properties and hydrolysis rate of
      pure cellulose fibers.
AB  - The aim of this study is to compare the effect of different steam explosion
      treatments on the physicochemical properties and the hydrolysis rate of a pure
      bleached cellulose. The results showed that moderate steam explosion treatments
      (severity factor below 5.2) did not appear to improve the enzymatic hydrolysis
      rate of the cellulose fibers. However, characterization of the samples showed a
      modification of the physicochemical properties of the cellulose, resulting in an
      increase of the water retention values (WRV) coupled to an increase of the
      overall crystallinity. For higher treatment intensities, an important thermal
      degradation of the cellulose was highlighted. This thermal degradation caused an
      important modification of the cellulose composition which leads to a decrease of
      the hydrolysis rate.

PMID- 22858490
TI  - Microalgal biohydrogen production considering light energy and mixing time as the
      two key features for scale-up.
AB  - This study focuses on a scale-up procedure considering two vital parameters light
      energy and mixing for microalgae cultivation, taking Chlamydomonas reinhardtii as
      the model microorganism. Applying two stage hydrogen production protocol to 1L
      flat type and 2.5L tank type photobioreactors hydrogen production was
      investigated with constant light energy and mixing time. The conditions that
      provide the shortest transfer time to anaerobic culture (light energy; 2.96 kJ s(
      1)m(-3) and mixing time; 1 min) and highest hydrogen production rate (light
      energy; 1.22 kJ s(-1)m(-3) and mixing time; 2.5 min) are applied to 5L
      photobioreactor. The final hydrogen production for 5L system after 192 h was
      measured as 195 +/- 10 mL that is comparable with the other systems is a good
      validation for the scale-up procedure.

PMID- 22858491
TI  - Modification of bio-char derived from fast pyrolysis of biomass and its
      application in removal of tetracycline from aqueous solution.
AB  - In this work, bio-char, a mass productive by-product of biomass fast pyrolysis,
      was adopted as an adsorbent to remove tetracycline (TC) from aqueous solution. To
      enhance the adsorption capacity, a simple modification of bio-char with acid and
      alkali was carried out. Bio-char samples were characterized by Fourier transform
      infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nitrogen adsorption
      desorption isotherm. The results show that the alkali treated bio-char possesses
      larger surface area than those of raw and acid treated bio-chars, and accordingly
      exhibits a more excellent adsorption performance (58.8 mg/g) than the other two
      bio-chars and other adsorbents reported previously. The graphite-like structure
      of bio-char facilitates the formation of pi-pi interactions between ring
      structure in tetracycline molecule and graphite-like sheets. The surface area
      showed significant effects on TC adsorption as well as O-containing functional
      groups, whereas the initial pH of solution has small effects on TC adsorption
      under the experimental conditions.

PMID- 22858492
TI  - Operational experience with a seasonally operated full-scale membrane bioreactor
      plant.
AB  - A seasonally operated full-scale membrane bioreactor plant (flat sheet, 0.03 MUm)
      treating municipal wastewater from a recreation facility was monitored for 2
      years. In particular, membrane bioreactor operation characteristics and
      development and changes in extracellular polymeric substances and soluble
      microbial product concentrations were observed, which were both dependent on
      volume and quality of incoming wastewater. Microbiological effluent quality,
      nutrient removal efficiency and activated sludge characteristics were analysed on
      a regular basis. Correlations between activated sludge quality, extracellular
      polymeric substance and soluble microbial product concentrations were identified.
      Pathogen related changes in effluent quality during plant operation were also
      observed. Nutrient removal efficiency was very good, despite fluctuations in
      influent flow.

PMID- 22858493
TI  - Production of light olefins by catalytic conversion of lignocellulosic biomass
      with HZSM-5 zeolite impregnated with 6wt.% lanthanum.
AB  - Catalytic conversion of rice husk, sawdust, sugarcane bagasse, cellulose,
      hemicellulose and lignin into olefins was performed with HZSM-5 containing 6 wt.%
      lanthanum. The olefins yields for different feedstocks decreased in the order:
      cellulose>hemicellulose>sugarcane bagasse>rice husk>sawdust>lignin. Biomass
      containing higher content of cellulose or hemicellulose produced more olefins
      than feedstocks with higher content of lignin. Among the biomass types, sugarcane
      bagasse provided the highest olefin yield of 0.12 kg olefins/(kg dry biomass) and
      carbon yield of 21.2C-mol%. Temperature, residence time and the catalyst/feed
      ratio influenced olefin yield and selectivity. While the HZSM-5 zeolite was
      catalytically active, the incorporation of lanthanum at 2.9, and 6.0 wt.%
      increased the production of olefins from rice husk by 15.6% and 26.5%,
      respectively. The conversion of biomass to light olefins potentially provides an
      alternative and sustainable route for production of the key petrochemicals.

PMID- 22858494
TI  - Isolation of a novel strain of Monoraphidium sp. and characterization of its
      potential application as biodiesel feedstock.
AB  - A novel green microalgae strain from Lake Fuxian has been isolated and identified
      as a potential feedstock for biodiesel production. The novel strain was named
      Monoraphidium sp. FXY-10 based on its morphological and genomic characterization.
      The lipid productivities, fatty acid profiles, and microalgae recovery efficiency
      (eta(a)) of FXY-10 were investigated and compared under autotrophic and
      heterotrophic conditions. FXY-10 under autotrophic conditions exhibited a higher
      cellular lipid content (56.8%) than those under heterotrophic conditions
      (37.56%). However, FXY-10 growing under heterotrophic conditions exhibited more
      than 20-fold increase in lipid productivity compared with that under autotrophic
      conditions (148.74 mg L(-1)d(-1) versus 6.88 mg L(-1)d(-1)). Moreover, higher
      saturated and monounsaturated fatty acids (77.5%) of FXY-10 was obtained under
      heterotrophic culture conditions, suggesting its potential as a biodiesel
      feedstock. Gravity sedimentation was proposed as the harvesting biomass method
      based on the 97.9% microalgae recovery efficiency of heterotrophic cells after
      settling for 24h.

PMID- 22858495
TI  - Aerobic degradation of phenolics and aromatic hydrocarbons in presence of
      cyanide.
AB  - Present study focused on the degradation of a mixture of phenol, cresol, xylenol,
      quinoline, and indole along with cyanide, commonly found in coke oven wastewater,
      using aerobic mixed culture. It was found that xylenol and indole were difficult
      to degrade, when the concentrations were above 250 mg/L. It was observed that
      free cyanide (2.5mg/L and above) has the potency to holdup the oxidation of
      organics (250 mg/L) until the cyanide concentration drops to a minimum level.
      Final TOC in the mixed pollutant system was less than 4 mg/L, indicating the
      absence of other organic byproducts. Experimental results highlight effect of
      free cyanide on removal of organics and the combined toxic influence of cyanide
      and organics on the microbes treating coking wastewater. The proposed
      mathematical model was able to predict the biodegradation of mixed pollutant
      system satisfactorily.

PMID- 22858496
TI  - A rapid and consistent near infrared spectroscopic assay for biomass enzymatic
      digestibility upon various physical and chemical pretreatments in Miscanthus.
AB  - Near infrared spectroscopy (NIRS) has been broadly applied as a quick assay for
      biological component and property analysis. However, NIRS remains unavailable for
      in-depth analysis of biomass digestibility in plants. In this study, NIRS was
      used to determine biomass enzymatic digestibility using 199 Miscanthus samples,
      which represents a rich germplasm resource and provides for a stable calibration
      model. The intensive evaluation indicates that the calibration and validation
      sets are comparable. Using the modified partial least squares method, seven
      optimal equations were generated with high determination coefficient on
      calibration (R(2)) at 0.75-0.89, cross-validation (R(2)cv) at 0.69-0.87, and the
      ratio performance deviation (RPD) at 1.80-2.74, which provide multiple options
      for NIRS prediction of biomass digestibility under different pretreatments. As
      biomass digestibility is a crucial parameter for biofuel processing, NIRS is a
      powerful tool for the high-throughput screening of biomass samples in plants.

PMID- 22858497
TI  - Demonstration of sequential adaptation strategy for developing salt tolerance in
      bacteria for wastewater treatment: a study using Escherichia coli as model.
AB  - A wastewater isolate identified as Escherichia coli HPC781 was adapted for high
      salt concentration through sequential transfers in Luria Broth (LB). The cells
      were grown in LB with 5% sodium chloride (NaCl) and were analyzed for the
      acquired salt resistance network through gene expression profiles. Microarray
      studies revealed TCA, glyoxylate shunt and acetyl Co-A metabolism as key nodes
      for stress combat to arrive at compromised physiology. It also proposed that the
      cells were receiving signals from salt environment via OmpR-EnvZ two component
      systems and stress dependent general regulatory protein rpoH and rpoE. The salt
      adapted culture, when challenged with wastewater having additional 5% salt showed
      growth. The work represents a tactic to adjust biochemical network towards stress
      and reveals its applicability via real-time PCR measurement of genes in
      wastewater. The study proposes that the recycled biomass with an adaptation
      strategy could be applied for treatment of wastewater with high salt levels.

PMID- 22858498
TI  - Response surface methodology as optimization strategy for asymmetric bioreduction
      of (4S)-(+)-carvone by Cryptococcus gastricus.
AB  - Response surface methodology was applied in optimizing the asymmetric
      bioreduction of (4S)-(+)-carvone to dihydrocarvone (with low incidence of
      unsought side reactions) by using whole-cells of Cryptococcus gastricus. A
      factorial design (2(5)) including five independent variables was performed:
      X(1)=incubation time; X(2)=pH; X(3)=amount of whole-cells; X(4)=concentration of
      (4S)-(+)-carvone; X(5)=concentration of cofactor-recycling system. The
      utilization of glucose and glycerol as cofactor-recycling systems was checked. On
      the basis of the results of factorial design, three independent variables (X(1),
      X(3) and X(4)) out of five were further selected for performing a central
      composite design (CCD). First and second order polynomial equations obtained by
      CCD were used to select the optimal values of independent variables in order to
      maximize the bioreduction yield of (4S)-(+)-carvone and, at the same time, to
      minimize the occurrence of side reactions (i.e. further reduction of
      dihydrocarvone to dihydrocarveol).

PMID- 22858499
TI  - Using ammonia for algae harvesting and as nutrient in subsequent cultures.
AB  - Microalgae have been considered as a promising feedstock for biofuels and
      greenhouse gas reduction. A low-cost harvesting technology without secondary
      contamination for down-stream extraction is a key requirement to make algal
      biofuel commercially viable. A novel harvesting method using ammonia as a
      flocculant to make the algal biomass settable was devised and studied. Another
      major advantage of this approach is that the ammonia added will be reused as
      fertilizer in the subsequent cultures. The results indicated that ammonia-induced
      flocculation led to more than 99% removal of algae at 12h. The OD(600) of algae
      growing in the ammonia-enriched flocculation medium treated with heating and
      CO(2) was 2 times than that of initial after 6 days. These results suggested that
      this flocculation method was efficient, convenient and allowed the reuse of the
      flocculated medium, therefore providing an option for economic harvesting and
      cultivation of microalgae.

PMID- 22858500
TI  - Biochemical diversity of the bacterial strains and their biopolymer producing
      capabilities in wastewater sludge.
AB  - The biochemical characterization of 13 extracellular polymeric substances (EPS)
      producing bacterial strains were carried out by BIOLOG. The bacterial strains
      were cultured in sterilized sludge for EPS production. Flocculation and
      dewatering capabilities of produced EPS (broth, crude slime and capsular) were
      examined using kaolin suspension combined with calcium (150 mg of Ca(2+)/L of
      kaolin suspension). BIOLOG revealed that there were 9 Bacillus, 2 Serratia and 2
      Yersinia species. Most of these bacterial strains had the capability to utilize
      wide spectrum of carbon and nitrogen sources. EPS concentration of more than 1g/L
      was produced by most of the bacterial strains. Concentration of EPS produced by
      different Bacillus strains was higher than that of Serratia and Yersinia. Broth
      EPS revealed flocculation activity more than 75% for Bacillus sp.7, Bacillus sp.4
      and Bacillus sp.6, respectively. Flocculation activity higher than 75% was
      attained using very low concentrations of broth EPS (1.12-2.70 mg EPS/g SS).

PMID- 22858501
TI  - Effect of salinity on enzymatic activities in a submerged fixed bed biofilm
      reactor for municipal sewage treatment.
AB  - The effect of salinity on the hydrolytic enzymatic activities (acid phosphatase,
      alkaline phosphatase, glucosidase, protease and esterase) released by the
      microorganisms in a submerged fixed bed bioreactor for real urban wastewater
      treatment was investigated. The influence of salt (NaCl) on the enzymatic
      activities was evaluated in four different experiments with concentrations of
      NaCl of 0, 3.7, 24.1 and 44.1g/L, remaining constant all other operating
      parameters of the bioreactor. The results show that enzymatic activities were
      reduced when the salinity was increased in the influent and consequently the
      biotransformation of organic matter in the submerged fixed bed bioreactor
      significantly decreased. A redundancy analysis was performed to evaluate the
      relationships between enzymatic activities and physic-chemical parameters
      analyzed in the influent. According to the results obtained with the Monte Carlo
      permutation test, salinity and sampling day significantly contributed to explain
      the variation of enzymatic activities, showing a negative correlation.

PMID- 22858502
TI  - Biosynthesis and characterization of polyhydroxyalkanoate containing high 3
      hydroxyhexanoate monomer fraction from crude palm kernel oil by recombinant
      Cupriavidus necator.
AB  - The potential of plant oils as sole carbon sources for production of P(3HB-co
      3HHx) copolymer containing a high 3HHx monomer fraction using the recombinant
      Cupriavidus necator strain Re2160/pCB113 has been investigated. Various types and
      concentrations of plant oils were evaluated for efficient conversion of P(3HB-co
      3HHx) copolymer. Crude palm kernel oil (CPKO) at a concentration of 2.5 g/L was
      found to be most suitable for production of copolymer with a 3HHx content of
      approximately 70 mol%. The time profile of these cells was also examined in order
      to study the trend of 3HHx monomer incorporation, PHA production and PHA synthase
      activity. (1)H NMR and (13)C NMR analyses confirmed the presence of P(3HB-co
      3HHx) copolymer containing a high 3HHx monomer fraction, in which monomers were
      not randomly distributed. The results of various characterization analyses
      revealed that the copolymers containing a high 3HHx monomer fraction demonstrated
      soft and flexible mechanical properties.

PMID- 22858503
TI  - Conversion of lignin to aromatic-based chemicals (L-chems) and biofuels (L
      fuels).
AB  - Conversion of lignin into chemicals and biofuels was performed using the
      commercial Kraft lignin, Indulin AT. Lignin was depolymerised in an aqueous
      alkaline solution using a continuous flow reactor generating four fractions.
      First is the gas fraction (mainly CO(2)), the second includes methanol, acetic
      acid and formic acid, thus defined as small organic compounds and third one (up
      to 19.1 wt.% of lignin) is mostly composed of aromatic monomers. The fourth
      fraction (45-70 wt.%) contains oligomers (polyaromatic molecules) and modified
      lignin. Pyrocatechol was the most abundant product at high severities (315
      degrees C) with selectivity up to 25.8%. (31)P NMR showed the loss of almost all
      aliphatic OH groups and apparition of catechol groups during depolymerisation.

PMID- 22858504
TI  - A real explosion: the requirement of steam explosion pretreatment.
AB  - The severity factor is a common term used in steam explosion (SE) pretreatment
      that describes the combined effects of the temperature and duration of the
      pretreatment. However, it ignores the duration of the explosion process. This
      paper describes a new parameter, the explosion power density (EPD), which is
      independent of the severity factor. Furthermore, we present the adoption of a
      5m(3) SE model for a catapult explosion mode, which completes the explosion
      within 0.0875 s. The explosion duration ratio of this model to a conventional
      model of the same volume is 1:123. The comparison between the two modes revealed
      a qualitative change by explosion speed, demonstrating that this real explosion
      satisfied the two requirements of consistency, and suggested a guiding mechanism
      for the design of SE devices.

PMID- 22858505
TI  - Sexual practices of young educated men: implications for further research and
      health education in Kingdom of Saudi Arabia (KSA).
AB  - BACKGROUND: Considering the high prevalence of sexually transmitted infections
      (STIs) and other associated health problems among young people globally, it is
      important to identify sexual practices that could potentially compromise health.
      This study explored the sexual practices of young men in Riyadh city, the Kingdom
      of Saudi Arabia (KSA).  Materials and methodology A cross-sectional study among
      young, male students was conducted using a pre-tested, structured, self
      administered questionnaire. Descriptive analysis and adjusted odds ratio (OR)
      were calculated. RESULTS: Among 225 study participants, 31% had engaged in
      premarital sexual activity at least once and 61% viewed pornographic
      movies/materials. Only 51% knew that condom use could prevent STIs, 20% were not
      aware that HIV could be transmitted through both homosexual and heterosexual
      contacts. Premarital sexual activity was associated with the use of illegal drugs
      (OR: 2.51), viewing of pornographic movies (OR: 6.79) and traveling alone abroad
      (OR: 3.10). CONCLUSION: and recommendations Our study was the first to report the
      existence of premarital sexual practices among young educated men in KSA. There
      is a need to identify in detail the risks and the knowledge gaps, and base sexual
      health awareness among youth on such knowledge in order to prevent the spread of
      STIs and HIV.

PMID- 22858506
TI  - Autologous cord blood transplantation in a child with stage 4 neuroblastoma.

PMID- 22858507
TI  - Quantification of minimal residual disease levels by flow cytometry at time of
      transplant predicts outcome after myeloablative allogeneic transplantation in
      ALL.
AB  - The potential impact on patient outcome of different Minimal residual disease
      (MRD) levels at time of transplant in patients with lymphoblastic leukemia
      undergoing allogeneic hematopoietic SCT (HSCT) remains uncertain. In this study,
      we quantified MRD levels at time of transplant using multiparameter flow
      cytometry (MFC). Mononuclear cells from marrow aspirates were obtained from 102
      adult and child patients before their conditioning regimen. Quantification of MRD
      levels was carried out by detecting patient-specific leukemia-associated
      immunophenotypes using four-color MFC. Thirty patients exhibited measurable
      levels of MRD at the time of transplant, with low levels (0.01 to ?0.1%) in 12
      cases, intermediate levels (>0.1 to ?1%) in 8 cases and high levels (>1%) in 10
      cases. The leukemia-free survival (LFS) rates were 65.9+/-7.0%, 42.9+/-15.7% and
      0% for negative, low levels ?0.1% and intermediate-high levels >0.1%,
      respectively (P<0.001, log-rank test). Overall survival (OS) was 52.3+/-7.6%,
      28.6+/-13.8% and 0% for MRD-negative, low levels ?0.1% and intermediate-high
      levels >0.1%, respectively (P<0.001, log-rank test). Multivariate Cox analysis
      confirmed that detection of leukemia cells by flow cytometry at transplant was
      the most significantly adverse factor for OS, LFS and EFS after transplant.

PMID- 22858508
TI  - The role of hematopoietic SCT in adult Burkitt lymphoma.
AB  - Adult Burkitt lymphoma (BL) is an aggressive disease characterized by frequent
      extranodal presentation, bulky disease and a rapid clinical course. Although
      intensive chemotherapeutic regimes result in long-term disease-free survival in
      most patients, a significant proportion of patients will have high-risk disease
      that may be refractory or that will relapse. In these patients, the role of
      hematopoietic SCT is not well defined, especially in the era of modern
      chemoimmunotherapy. Upfront auto-SCT has been reported to be feasible in patients
      who have high-risk features at presentation, and in whom it is a clinical option.
      In patients with relapsed disease, auto-SCT can result in a PFS of 30-40%. Allo
      SCT is an option in relapsing patients with a sibling or matched related donor
      who may not be eligible for, or may have previously received, an auto-SCT; the
      role of RIC and T-cell depletion is not well defined. Disease status at
      transplant is the most significant predictor of outcome in patients undergoing
      SCT. Here we review the available evidence pertaining to SCT in patients with BL,
      including in those who are HIV positive (HIV+) and those with B-cell lymphoma
      unclassified (BCLU). Prospective studies in the era of modern intensive
      chemoimmunotherapeutic regimes are required to delineate the precise role of
      transplantation for BL. Developments in molecular diagnostics, incorporation of
      FDG-PET and minimal residual disease monitoring along with new therapies may
      further assist in refining treatment algorithms.

PMID- 22858509
TI  - Donor selection for patients undergoing allogeneic hematopoietic SCT: assessment
      of the priorities of Canadian hematopoietic SCT physicians.

PMID- 22858510
TI  - Pegfilgrastim compared with filgrastim for cytokine-alone mobilization of
      autologous haematopoietic stem and progenitor cells.
AB  - Haematopoietic stem and progenitor cells (HSPC) mobilization, using cytokine
      alone, is a well-tolerated regimen with predictable mobilization kinetics. Single
      dose pegfilgrastim mobilizes HSPC efficiently; however, there is surprisingly
      little comparative data on its use without chemotherapy for HSPC mobilization.
      Pegfilgrastim-alone and filgrastim-alone mobilization regimens were compared in
      52 patients with haematological malignancy. Pegfilgrastim 12 mg (n=20) or 6 mg
      (n=2) was administered Day 1 (D1) in 22 patients (lymphoma n=17; myeloma n=5).
      Thirty historical controls (lymphoma n=18; myeloma n=12) received filgrastim 10
      mcg/kg daily from D1. Peripheral blood (PB) CD34(+) counts reached threshold (?5
      * 10(6)/L) and apheresis commenced on D4(4-5) and D4(4-6). Median PB CD34(+) cell
      count on D1 of apheresis was similar (26.0 * 10(6)/L (2.5-125.0 * 10(6)/L) and
      16.2 * 10(6)/L (2.6-50.7 * 10(6)/L); P=0.06), for pegfilgrastim and filgrastim
      groups, respectively. Target yield (?2 * 10(6) per kg CD34(+) cells) was
      collected in 20/22 (91%) pegfilgrastim patients and 24/30 (80%) in the filgrastim
      group (P=0.44), in a similar median number of aphereses (3(1-4) versus 3(2-6),
      respectively; P=0.85). A higher proportion of pegfilgrastim patients tended to
      yield ?4 * 10(6) per kg CD34(+) cells; 16/22 (73%) versus 14/30 (47%) filgrastim
      patients (P=0.09). One pegfilgrastim patient developed hyperleukocytosis that
      resolved without incident. Pegfilgrastim-alone is a simple, well-tolerated, and
      attractive option for outpatient-based HSPC mobilization with similar
      mobilization kinetics and efficacy to regular filgrastim.

PMID- 22858511
TI  - Gastrointestinal stromal tumors: the role of the gastroenterologist in diagnosis
      and risk stratification.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that are best
      classified as sarcomas with variable aggressiveness. They are typically treated
      with surgical resection and adjuvant tyrosine kinase inhibitors or, for
      advanced/metastatic GISTs, with tyrosine kinase inhibitors alone.
      Gastroenterologists are often the first to detect GISTs and are, therefore,
      tasked with diagnosis and facilitation of early intervention. Diagnostic tools
      including various imaging techniques such as endoscopic ultrasound (EUS) and EUS
      assisted tissue sampling are critical for an accurate diagnosis. In the case of
      small tumors, EUS-assisted resection or ligation techniques to treat asymptomatic
      small tumors have been described. This paper reviews current evidence for the
      diagnosis and management of GISTs, with an emphasis on the role of the
      gastroenterologist.

PMID- 22858512
TI  - Long-term treatment of patients with a history of ulcerative colitis who develop
      gastritis and pan-enteritis after colectomy.
AB  - BACKGROUND: Ulcerative colitis (UC) is generally described as a superficial
      diffuse inflammation restricted to the colon and rectum. However, several case
      reports have described a distinct and rare type of UC-related pan-enteritis,
      typically occurring after colectomy. Corticosteroids are effective for induction
      of remission of this condition, but it is not clear how these patients should be
      managed long term. GOALS: To further describe and define the entity of UC-related
      pan-enteritis and to investigate the efficacy of azathioprine for maintenance of
      remission. RESULTS: We describe 5 patients with superficial diffuse ulcerative
      inflammation of the stomach, small bowel, and pouch if present. Four of the 5
      patients developed enteritis after colectomy for ulcerative pancolitis. Pathology
      showed severe mucosal inflammation with infiltration of neutrophils and plasma
      cells from the stomach to the ileum. Video capsule endoscopy in 1 patient
      confirmed the presence of mucosal inflammation throughout the small bowel. All
      patients were started on a standardized treatment with intravenous
      corticosteroids for induction of remission and azathioprine for maintenance
      therapy. The conditions of all the patients rapidly improved, and subsequently, 4
      patients were in full remission on azathioprine monotherapy, despite failure of
      this UC therapy before surgery, whereas 1 patient continues to have a steroid
      dependent disease. CONCLUSIONS: The outcomes of 5 cases of UC-related pan
      enteritis as described in this report support a role for azathioprine in
      remission maintenance. Future research is needed to improve our understanding of
      this rare but distinct intestinal inflammatory disorder.

PMID- 22858513
TI  - The efficacy and safety of carbon dioxide insufflation during colonoscopy with
      consecutive esophagogastroduodenoscopy in moderately sedated outpatients: a
      randomized, double-blind, controlled trial.
AB  - GOALS AND BACKGROUND: Colonoscopy with consecutive esophagogastroduodenoscopy
      (CCEGD) can be more convenient than performing each procedure individually. There
      has been no randomized controlled trial comparing carbon dioxide (CO2) versus air
      insufflations during CCEGD in sedated patients. CO2 insufflation instead of air
      during CCEGD may reduce abdominal pain and be more comfortable. We investigated
      the efficacy and safety of CO2 insufflation during CCEGD in moderately sedated
      outpatients. STUDY: This was a randomized, double-blind, controlled trial. A
      total of 96 outpatients were randomly assigned to the groups of CO2 or air
      insufflation. Postprocedure pain was assessed using a 0 to 10 visual analogue
      scale, and the proportion of pain-free patients was compared between the groups.
      Waist circumferences and end-tidal CO2 (ETCO2) were measured. RESULTS: Among 96
      patients, cecal intubation failed in 2 patients, who were excluded from the
      analysis. Forty-eight patients in the CO2 and 46 patients in the air group
      completed the study. There was significant difference between the 2 groups
      regarding the proportion of pain-free patients 30 minutes after the procedures
      [air group, 35/46 (76.1%) vs. CO2 group, 44/48 (91.6%)] (P=0.03). However, there
      was no significant difference in the proportion at 6 and 24 hours after the
      procedures. The mean increase in waist circumference was greater with air than
      with CO2 (1.54 vs. 0.18 cm, P<0.001). The ETCO2 measured immediately after the
      procedures was slightly higher in the CO2 group than in the air group (38.6 vs.
      37.2 mm Hg, P=0.02), but the values were within the normal range. No significant
      adverse events occurred. CONCLUSIONS: CO2 insufflation during CCEGD reduced
      postprocedural pain and distension compared with air. It was comfortable and safe
      to use in moderately sedated outpatients.

PMID- 22858514
TI  - Infliximab and adalimumab use during breastfeeding.

PMID- 22858515
TI  - Mycobacterium avium ss paratuberculosis-associated diseases: piecing the Crohn's
      puzzle together.
AB  - The relation of Mycobacterium avium ss paratuberculosis (MAP) to Crohn's Disease
      (CD) and other MAP-associated conditions remains controversial. New data, coupled
      with the analogous Helicobacter pylori (H. pylori) story, has permitted us to
      piece together the MAP puzzle and move forward with a more scientific way of
      treating inflammatory bowel disease, particularly CD. As infection moves centre
      stage in inflammatory bowel disease, the dated "aberrant reaction" etiology has
      lost scientific credibility. Now, our growing understanding of MAP-associated
      diseases demands review and articulation. We focus here on (1) the concept of MAP
      associated diseases; (2) causality, Johne Disease, the "aberrant reaction"
      hypothesis; and (3) responses to published misconceptions questioning MAP as a
      pathogen in CD.

PMID- 22858516
TI  - Double-balloon enteroscopy in patients with previous incomplete colonoscopy:
      should we perform them more often?

PMID- 22858517
TI  - Nonbismuth quadruple "concomitant" therapy versus standard triple therapy, both
      of the duration of 10 days, for first-line H. pylori eradication: a randomized
      trial.
AB  - GOALS: To compare the efficacy, compliance, and tolerability of a quadruple,
      nonbismuth-containing concomitant therapy with standard triple therapy, both of
      the duration of 10 days, for Helicobacter pylori eradication. BACKGROUND:
      Eradication rates obtained with standard therapies are declining as antibiotic
      resistance becomes more prevalent worldwide. New first-line treatment strategies
      are needed. STUDY: Two hundred fifty-seven patients with H. pylori infection were
      included in the study. Patients were randomized to receive 10-day concomitant
      therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500
      mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy
      comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg,
      all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after
      the start of treatment. RESULTS: Two hundred forty-six patients completed the
      study. The intention-to-treat cure rates were 90.5% [95% confidence interval
      (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure
      rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%),
      respectively. The eradication rate was significantly higher in the concomitant
      group compared with the triple therapy group in both the intention-to-treat
      (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally
      of mild/moderate intensity and did not interfere significantly with compliance,
      which was excellent for both treatment groups (96.6% and 98.5%, respectively,
      P=0.44). CONCLUSIONS: Performance of a 10-day conventional triple regimen is
      suboptimal. A 10-day concomitant regimen achieved a significantly higher
      eradication rate and seems to be an effective, safe, and well-tolerated treatment
      option for H. pylori eradication.

PMID- 22858518
TI  - The relationship between type 2 diabetes mellitus and failure to proton pump
      inhibitor treatment in gastroesophageal reflux disease.
AB  - BACKGROUND: There is limited information regarding the contribution of diabetes
      mellitus (DM) to proton pump inhibitor (PPI) failure in gastroesophageal reflux
      disease (GERD) patients. AIM: To determine whether type 2 DM is a risk factor for
      PPI failure and the potential predictive factors for PPI failure among type 2 DM
      patients with GERD. DESIGN: A case-control study was performed using hospital
      medical records of GERD patients treated with a PPI. The prevalence of type 2 DM
      and other risk factors (established >1 y before study enrollment) was determined
      in the PPI failure (treatment with more than once daily PPI) as compared with PPI
      responders. RESULTS: A total of 732 GERD patients receiving PPI therapy,
      including 285 who failed PPI treatment, were included. The overall prevalence of
      PPI failure was significantly higher in diabetic versus nondiabetic patients. The
      relationship between PPI failure and type 2 DM depended on body mass index. Only
      in obese patients the odds ratio of PPI failure was significantly higher in type
      2 DM as compared with non-DM patients. In the subgroup of GERD patients with type
      2 DM (n=349), PPI failure was significantly associated with female sex, the
      presence of general comorbidities, and adequate DM control. Duration of DM, type
      of antidiabetic medication prescribed, and DM-associated complications were not
      associated with PPI failure. CONCLUSIONS: PPI failure was significantly
      associated with type 2 DM in obese patients. Among GERD patients with type 2 DM,
      failure of PPI treatment was significantly associated with female sex and the
      presence of general comorbidities.

PMID- 22858519
TI  - Development of pylomatrixoma after the subcutaneous injection of methotrexate for
      the treatment of juvenile idiopathic arthritis.

PMID- 22858520
TI  - Collodion baby: an update with a focus on practical management.
AB  - Collodion baby is an uncommon clinical presentation of several genetic
      conditions, primarily disorders of cornification. The severely compromised
      epidermal barrier presents the greatest challenge during the newborn period and
      advances in neonatal care have significantly improved the prognosis. This review
      summarizes the clinical characteristics, complications, outcomes, and
      differential diagnosis of the collodion baby. A practical approach to management
      based on the literature and clinical experience is presented.

PMID- 22858521
TI  - Rapid and nondestructive analysis of pharmaceutical products using near-infrared
      diffuse reflectance spectroscopy.
AB  - Near-infrared diffuse reflectance spectroscopy (NIRDRS) was applied to
      classification and quantification of azithromycin tablets with the aid of
      chemometric multivariate analysis. Repeatability was investigated by repeated
      measurements, and the effect of morphology was examined by preparing the tablets
      in four forms, i.e. tablet product, tablet without coating, powder of tablet
      without coating, and powder of tablet. Furthermore, baseline elimination by
      continuous wavelet transform (CWT) and wavenumber selection was discussed for
      improving the repeatability and accuracy of the method. The results show that the
      spectra of the samples in the four forms can be measured with an acceptable
      repeatability, and classification of manufacture sites and quantitative analysis
      of the active pharmaceutical ingredient (API) can be achieved by principal
      component analysis (PCA) and partial least squares (PLS) regression,
      respectively. More importantly, baseline elimination and wavenumber selection can
      significantly simplify the calculation and improve the results.

PMID- 22858523
TI  - How do the basal ganglia regulate sleep-wake behavior?
AB  - The basal ganglia (BG) are involved in motor function, habit formation, and
      reward or addictive behaviors, but the question as to how the BG integrate
      arousal with these fundamental striatal functions has only recently received much
      attention. Findings based on electrophysiology, neurotoxic lesioning, and the use
      of transgenic animals have established that the striatum and globus pallidus are
      key structural elements for the control of sleep and wakefulness. Here, we
      discuss emerging anatomical and molecular mechanisms of sleep-wake regulation at
      work in the BG. Furthermore, we propose a model whereby adenosine and dopamine
      receptors in the nucleus accumbens (NAc) are involved in the integration of
      behavioral processes and the induction of wakefulness through cortical
      activation.

PMID- 22858524
TI  - The role of socioeconomic status in SAT-grade relationships and in college
      admissions decisions.
AB  - This article examines the role of socioeconomic status (SES) in the relationships
      among college admissions-test scores, secondary school grades, and subsequent
      academic performance. Scores on the SAT (a test widely used in the admissions
      process in the United States), secondary school grades, college grades, and SES
      measures from 143,606 students at 110 colleges and universities were examined,
      and results of these analyses were compared with results obtained using a 41
      school data set including scores from the prior version of the SAT and using
      University of California data from prior research on the role of SES. In all the
      data sets, the SAT showed incremental validity over secondary school grades in
      predicting subsequent academic performance, and this incremental relationship was
      not substantially affected by controlling for SES. The SES of enrolled students
      was very similar to that of specific schools' applicant pools, which suggests
      that the barrier to college for low-SES students in the United States is a lower
      rate of entering the college admissions process, rather than exclusion on the
      part of colleges.

PMID- 22858522
TI  - Striatal microcircuitry and movement disorders.
AB  - The basal ganglia network serves to integrate information about context, actions,
      and outcomes to shape the behavior of an animal based on its past experience.
      Clinically, the basal ganglia receive the most attention for their role in
      movement disorders. Recent advances in technology have opened new avenues of
      research into the structure and function of basal ganglia circuits. One emerging
      theme is the importance of GABAergic interneurons in coordinating and regulating
      network function. Here, we discuss evidence that changes in striatal GABAergic
      microcircuits contribute to basal ganglia dysfunction in several movement
      disorders. Because interneurons are genetically and neurochemically unique from
      striatal projection neurons, they may provide promising therapeutic targets for
      the treatment of a variety of striatal-based disorders.

PMID- 22858525
TI  - Effect of laser irradiation on crystalline structure of enamel surface during
      whitening treatment with hydrogen peroxide.
AB  - OBJECTIVE: This study is to evaluate the effect of laser activation on the
      whitening and crystalline structure of enamel surface during whitening treatment
      with hydrogen peroxide. METHODS: Bovine teeth were treated with whitening gel
      containing 35% hydrogen peroxide. A whitening gel was applied on the enamel
      surface for a period of 5 min, and then irradiated using a diode laser (740 nm)
      during whitening treatment for 0, 30, 60, 120 and 180s for the GL0-W, GL30-W,
      GL60-W, GL120-W and GL180-W groups, respectively. The total whitening application
      time was 30 min for all groups. RESULTS: Laser-irradiated enamel groups showed a
      similar lightness compared to the GL0-W group. The thickness of porous layer
      observed on the enamel surface of GL0-W group was decreased by increasing the
      laser irradiation time. While the Ca and P contents of the GL0-W group were lower
      than those of the non-whitening treated group (GL0-C), the Ca and P contents of
      the GL180-W group were similar to those of the GL180-C group. The enamel
      crystallinity was dramatically decreased by whitening treatment without laser
      irradiation. However, the decrease of crystallinity was protected by laser
      irradiation during whitening treatment. Raman measurement verified that laser
      irradiation could prevent the loss of mineral compositions on enamel and maintain
      its crystalline structure. SIGNIFICANCE: The professional whitening treatment
      with hydrogen peroxide and diode laser activation improves not only the whitening
      effect but also protects the change of enamel structure compared to the treatment
      with only gel.

PMID- 22858526
TI  - A study of hydrogen peroxide chemistry and photochemistry in tea stain solution
      with relevance to clinical tooth whitening.
AB  - OBJECTIVE: Tooth whitening using hydrogen peroxide is a complex process, and
      there is still some controversy about the roles of pH, temperature, chemical
      activators, and the use of light irradiation. In this work the basic interactions
      between whitening agents and stain molecules are studied in simple solutions,
      thus avoiding the physics of diffusion and light penetration in the tooth to give
      clarity on the basic chemistry which is occurring. METHOD: The absorbance of tea
      stain solution at 450 nm was measured over a period of 40 min, with various
      compositions of whitening agent added (including hydrogen peroxide, ferrous
      gluconate and potassium hydroxide) and at the same time the samples were
      subjected to blue light (465 nm) or infra-red light (850 nm) irradiation, or
      alternatively they were heated to 37 degrees C. RESULTS: It is shown that the
      reaction rates between chromogens in the tea solution and hydrogen peroxide can
      be accelerated significantly using ferrous gluconate activator and blue light
      irradiation. Infra red irradiation does not increase the reaction rate through
      photochemistry, it serves only to increase the temperature. Raising the
      temperature leads to inefficiency through the acceleration of exothermic
      decomposition reactions which produce only water and oxygen. CONCLUSION: By
      carrying out work in simple solution it was possible to show that ferrous
      activators and blue light irradiation significantly enhance the whitening
      process, whereas infra red irradiation has no significant effect over heating.
      The importance of controlling the pH within the tooth structure during whitening
      is also demonstrated.

PMID- 22858527
TI  - The additional effect of ozone in combination with adjunct remineralisation
      products on inhibition of demineralisation of the dental hard tissues in situ.
AB  - OBJECTIVES: In the United Kingdom Ozone therapy combines the use of ozone gas and
      adjunct products called Reductant and the Patient Kit, which all contain
      fluoride. We studied the effect of these products with and without the use of
      ozone in inhibiting demineralisation of human enamel and dentine under a
      cariogenic challenge in situ. METHODS: A single-blind, randomised, three arms,
      cross-over study design was used. Fourteen volunteers were provided with a lower
      removable intra-oral appliance carrying one enamel and one dentine slabs.
      Baseline measurements of enamel and dentine hardness slabs were recorded. The
      study regime of 14 days of dipping into 10% sucrose solution 5 times a day was
      applied. The three arms were two test groups Ozone/Reductant/Patient Kit,
      Reductant/Patient Kit, and a fluoride free toothpaste group as a control. At the
      end of the 2nd week the slabs were collected, microhardness measured and the
      differences from the baselines were calculated. RESULTS: There were statistically
      significant differences in the mean changes of enamel and dentine hardness when
      both the test groups were compared individually with the control. However, no
      statistical significant differences in either parameter were found when
      Ozone/Reductant/Patient Kit group was compared with Reductant/Patient Kit
      treatment. CONCLUSIONS: We conclude from these results that ozone had no
      additional effect on the inhibition of enamel and dentine demineralisation than
      when Reductant/Patient Kit, containing high concentrations of fluoride, were used
      on their own.

PMID- 22858528
TI  - Transcriptome analysis in pea allows to distinguish chilling and acclimation
      mechanisms.
AB  - In order to distinguish chilling and freezing tolerance mechanisms in pea,
      responses to cold exposure were compared between the freezing tolerant line
      Champagne and the sensitive line Terese. Global gene expression was considered in
      the two lines and associated with morphological, histological and biochemical
      approaches. The chilling tolerance in both lines was related to responses of the
      CBF, COR and LEA genes belonging to the CBF regulon, with greater earliness of
      expression in the Champagne genotype. The freezing tolerance, only observed in
      Champagne, was associated with acclimation processes such as cellular osmotic
      stabilization, photosynthesis modifications, antioxidants production,
      modifications in hormone metabolism, cell wall composition and dynamics.

PMID- 22858529
TI  - Interaction network of antimicrobial peptides of Arabidopsis thaliana, based on
      high-throughput yeast two-hybrid screening.
AB  - One mechanism used by plants to respond to infection is the production of
      antimicrobial peptides (AMPs). In addition to a role in defence, AMPs seem to
      have other biological functions. Furthermore, the number of cysteine-rich AMP
      like peptides appears to have been underpredicted in plant genomes. Such peptides
      could be involved in plant defence and/or in other biological processes. Here we
      generated an interaction network between 15 AMPs/AMP-like peptides and ca. 8000
      other Arabidopsis thaliana proteins (AtORFeome2.0) and found 53 putative novel
      interactions. These interactions involve five transcription factors, a subunit of
      the COP9 signalosome, a heat shock protein, a MAP kinase kinase, a thioredoxin
      and 4 uncharacterized proteins.

PMID- 22858530
TI  - Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of
      Boxes scores.
AB  - BACKGROUND: This study examined rates of dementia progression as ascertained by
      the Clinical Dementia Rating Sum of Boxes (CDR-SB) for symptomatic Alzheimer's
      disease (sAD), and assessed participant characteristics as predictors of CDR-SB
      progression. METHODS: Participants (n = 792) were enrolled in longitudinal
      studies at an Alzheimer's Disease Research Center, received a diagnosis of sAD
      with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up
      assessment. Progression in CDR-SB over time as a function of baseline global CDR
      was examined. RESULTS: A longitudinal increase (P < .0001) in CDR-SB was
      observed. The annual rate of change in CDR-SB scores was 1.43 (standard error
      [SE] = 0.05) in the CDR 0.5 sample and 1.91 (SE = 0.07) in the CDR 1 sample. For
      participants followed from the beginning of the CDR stage, time to progression to
      a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95%
      confidence interval [CI]: 3.18-4.33) than those who were CDR 1 at baseline (2.98
      years; 95% CI: 2.75-3.22). In the total CDR 0.5 sample, the significant
      predictors of progression to the next global CDR stage (P < .01) were age at
      first sAD diagnosis and apolipoprotein E4 genotype. CONCLUSIONS: The study
      findings are relevant to sAD clinical trial design and accurate, reliable
      ascertainment of the effect of disease-modifying treatments.

PMID- 22858531
TI  - No association between gain in body mass index across the life course and midlife
      cognitive function and cognitive reserve--the 1946 British Birth Cohort study.
AB  - BACKGROUND: The association between lifelong body mass index (BMI) and cognitive
      function has not been comprehensively studied. METHODS: In more than 2000 men and
      women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36,
      43, and 53 years with respect to the previous measure (gain at age 15 years with
      respect to BMI at age 11 years), and semantic fluency (animal naming) and
      cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal
      memory (word list recall) and speed/concentration (letter cancellation) at ages
      43 and 53 years. Measures of BMI gain were adjusted in stages for childhood
      intelligence, education, socioeconomic position (SEP), lifestyle, and vascular
      risk factors. RESULTS: Independent of childhood intelligence, BMI gain between
      ages 26 and 36 years was associated with lower memory scores (beta per SD
      increase in BMI in men = -0.11; 95% confidence interval [CI]: -0.19, -0.02),
      verbal fluency (beta in women = -0.11; 95% CI: -0.20, -0.02), and lower National
      Adult Reading Test score (beta in women = -0.08; 95% CI: -0.15, -0.01), but not
      with speed/concentration (beta in men = 0.02; 95% CI: -0.11, 0.07). Associations
      were largely explained by educational attainment and SEP (P >= .10). However, BMI
      gain at 53 years in men was independently associated with better memory (beta =
      0.12; 95% CI: 0.03, 0.22), and both underweight (beta = -1.54; 95% CI: -2.52, 
      0.57) and obese (beta = -0.30; 95% CI: -2.52, -0.57) women at 53 years had
      significantly lower memory scores. CONCLUSION: The adverse effect of higher BMI
      gain on midlife cognitive function and cognitive reserve is independent of
      childhood intelligence but not of education and SEP. The independent association
      between greater BMI gain in midlife and better cognitive function deserves
      further investigation.

PMID- 22858532
TI  - Organochlorine pesticides in seawater and the surrounding atmosphere of the
      marginal seas of China: spatial distribution, sources and air-water exchange.
AB  - Shipboard air and surface seawater samples collected over the Yellow Sea, East
      China Sea and South China Sea were analyzed for organochlorine pesticides (OCPs).
      In air, gamma-hexachlorocyclohexane (HCH), trans-chlordane (TC) and cis-chlordane
      (CC) had significantly (p<0.001) higher concentrations than alpha-HCH, o,p'
      Dichlorodiphenyltrichloroethane (DDT), p,p'-DDE, p,p'-DDT and alpha-endosulfan.
      Generally, alpha-HCH concentrations in the atmosphere were quite uniform over the
      Chinese marginal seas. However, the highest concentrations of gamma-HCH, TC, CC
      and DDT compounds were found in the southern parts of the marginal seas, and
      higher concentrations of alpha-endosulfan were observed in the northern part of
      the marginal seas. In water, the OCP concentrations varied over a narrow range,
      with hundreds picogram per liter levels. Air-water exchange gradients suggested
      net deposition or equilibrium for gamma-HCH and o,p'-DDT and net volatilization
      for alpha-HCH, CC, TC, p,p'-DDE and p,p'-DDT. Due to the potential source of
      those compounds from coastal water runoff, the ocean water played an important
      role of OCP sources for the atmosphere after a long period of OCP prohibition.

PMID- 22858533
TI  - Respirable antimony and other trace-elements inside and outside an elementary
      school in Flagstaff, AZ, USA.
AB  - Because people spend almost 90% of their time indoors, ambient air monitors may
      severely underestimate actual exposure to atmospheric particulate matter (PM).
      Therefore, it becomes increasingly important to better understand the
      microenvironments where people are spending their time. For preadolescent
      children, the best estimates of exposure may be inside of their school. In this
      study, 11 size fractions of PM were collected inside and outside of an elementary
      school in Flagstaff, AZ, USA. In particles<1 MUm (PM1), the total mass indoors
      was similar to the mass outdoors (indoor:outdoor, I:O, ratio=0.92 +/- 0.16). In
      the PM1-10 fraction, however, the mass concentration inside the school was highly
      elevated relative to outside the school (I:O ratios=13 +/- 3). Mass
      concentrations of 27 elements were analyzed by ICP-MS. For all metals except for
      antimony (Sb), the PM1 and PM1-10 I:O ratios are found to be similar to the
      overall PM mass (near 1 and 13, respectively). In addition, indoor and outdoor
      particle size distributions reveal a crustal character for every element except
      Cu, Zn, Pb, and Sb. Therefore, we hypothesize that most of the PM mass inside the
      school is a result of transport from outside the school followed by resuspension
      from floors and clothing. In the PM1 fraction, the indoor mass of Sb was 86 times
      greater than the outdoor mass and had an air concentration of 17 ngm(-3) -
      greater than many urban areas around the world. Cu:Sb ratios and size
      distribution functions suggest that the excess source of PM1 indoor Sb results
      from the suspension of embedded Sb (used as a flame retardant) in the carpeting.
      This is the first study to observe elevated submicron Sb in schools and further
      studies are required to determine if this is a widespread health risk.

PMID- 22858534
TI  - A diversified approach to evaluate biostimulation and bioaugmentation strategies
      for heavy-oil-contaminated soil.
AB  - A diversified approach involving chemical, microbiological and ecotoxicity
      assessment of soil polluted by heavy mineral oil was adopted, in order to improve
      our understanding of the biodegradability of pollutants, microbial community
      dynamics and ecotoxicological effects of various bioremediation strategies. With
      the aim of improving hydrocarbon degradation, the following bioremediation
      treatments were assayed: i) addition of inorganic nutrients; ii) addition of the
      rhamnolipid-based biosurfactant M(AT10); iii) inoculation of an aliphatic
      hydrocarbon-degrading microbial consortium (TD); and iv) inoculation of a known
      hydrocarbon-degrading white-rot fungus strain of Trametes versicolor. After 200
      days, all the bioremediation assays achieved between 30% and 50% total petroleum
      hydrocarbon (TPH) biodegradation, with the T. versicolor inoculation degrading it
      the most. Biostimulation and T. versicolor inoculation promoted the Brevundimonas
      genus concurrently with other alpha-proteobacteria, beta-proteobacteria and
      Cytophaga-Flexibacter-Bacteroides (CFB) as well as Actinobacteria groups.
      However, T. versicolor inoculation, which produced the highest hydrocarbon
      degradation in soil, also promoted autochthonous Gram-positive bacterial groups,
      such as Firmicutes and Actinobacteria. An acute toxicity test using Eisenia
      fetida confirmed the improvement in the quality of the soil after all
      biostimulation and bioaugmentation strategies.

PMID- 22858535
TI  - Using recorded sound spectra profile as input data for real-time short-term urban
      road-traffic-flow estimation.
AB  - Road traffic has a heavy impact on the urban sound environment, constituting the
      main source of noise and widely dominating its spectral composition. In this
      context, our research investigates the use of recorded sound spectra as input
      data for the development of real-time short-term road traffic flow estimation
      models. For this, a series of models based on the use of Multilayer Perceptron
      Neural Networks, multiple linear regression, and the Fisher linear discriminant
      were implemented to estimate road traffic flow as well as to classify it
      according to the composition of heavy vehicles and motorcycles/mopeds. In view of
      the results, the use of the 50-400 Hz and 1-2.5 kHz frequency ranges as input
      variables in multilayer perceptron-based models successfully estimated urban road
      traffic flow with an average percentage of explained variance equal to 86%, while
      the classification of the urban road traffic flow gave an average success rate of
      96.1%.

PMID- 22858536
TI  - Are chemicals in articles an obstacle for reaching environmental goals? - Missing
      links in EU chemical management.
AB  - It is widely acknowledged that the management of risks associated with chemicals
      in articles needs to be improved. The EU environmental policy states that
      environmental damage should be rectified at source. It is therefore motivated
      that the risk management of substances in articles also takes particular
      consideration to those substances identified as posing a risk in different
      environmental compartments. The primary aim of the present study was to
      empirically analyze to what extent the regulation of chemicals in articles under
      REACH is coherent with the rules concerning chemicals in the Sewage Sludge
      Directive (SSD) and the Water Framework Directive (WFD). We also analyzed the
      chemical variation of the organic substances regulated under these legislations
      in relation to the most heavily used chemicals. The results show that 16 of 24
      substances used in or potentially present in articles and regulated by the SSD or
      the WFD are also identified under REACH either as a substance of very high
      concern (SVHC) or subject to some restrictions. However, for these substances we
      conclude that there is limited coherence between the legislations, since the
      identification as an SVHC does not in itself encompass any use restrictions, and
      the restrictions in REACH are in many cases limited to a particular use, and thus
      all other uses are allowed. Only a minor part of chemicals in commerce is
      regulated and these show a chemical variation that deviates from classical legacy
      pollutants. This warrants new tools to identify potentially hazardous chemicals
      in articles. We also noted that chemicals monitored in the environment under the
      WFD deviate in their chemistry from the ones regulated by REACH. In summary, we
      argue that to obtain improved resource efficiency and a sustainable development
      it is necessary to minimize the input of chemicals identified as hazardous to
      health or the environment into articles.

PMID- 22858537
TI  - Severe and contrasted polymetallic contamination patterns (1900-2009) in the
      Loire River sediments (France).
AB  - The Loire River basin (117,800 km(2), France) has been exposed to multiple
      sources of metals during the last 150 years, originating from major mining
      districts (coal and non-ferrous metals) and their associated industrial
      activities. Geochemical archives are established here from the analysis of a 4m
      sediment core in the downstream floodplain and then compared to stream bed
      sediments from pristine monolithological sub-basins and from bed and bank
      sediments in impacted tributaries. The contamination is assessed for 55 major and
      trace elements through their enrichment factors to Al (EF), normalized to the pre
      anthropogenic background. Archives from 1900 to 2009 show enrichment (EF<1.3) not
      only for Ba, Be, Cs, Ga, Rb, REE, Sr, V, and Zr but also for U and Th, despite U
      mining activities until the 1990s. From 1900 to 1950, the level of contamination
      is severe for Hg, Au, Ag (10<EF<30), important for Sb and Sn (3<EF<7) and
      moderate for Cu, Pb and Zn (1.5<EF<3). This state was mostly attributed to coal
      uses and metal mining. During the period 1950-1980, severe polymetallic
      contamination is noted for Hg (EF up to 53), Cd (23), Ag (18), Zn (6.2), Cu
      (6.0), Sn (5.6), Pb(4.8), Sb(4.4) and for new impacted elements as Bi (23.8), As
      (3.7), Cr (3.4), W (3.1), Mo (2.6), Ni (2.8), Co (1.65) due to mines, smelters,
      industries and from urban sewers, collected mostly after 1950 (total population
      of 8.4 million people). The limited dilution by detrital material (Loire sediment
      load about 1.5 Mt/year) is an additional cause of such severe contamination.
      After 1950, river eutrophication is well marked by the general increase of
      endogenic calcite (EF (Ca)=4), diluting all other elements by 20%. From 1980 to
      2009, all contaminants, except Au (EF=100), decrease steadily.

PMID- 22858538
TI  - The therapeutic relationship in e-therapy for mental health: a systematic review.
AB  - BACKGROUND: E-therapy is defined as a licensed mental health care professional
      providing mental health services via e-mail, video conferencing, virtual reality
      technology, chat technology, or any combination of these. The use of e-therapy
      has been rapidly expanding in the last two decades, with growing evidence
      suggesting that the provision of mental health services over the Internet is both
      clinically efficacious and cost effective. Yet there are still unanswered
      concerns about e-therapy, including whether it is possible to develop a
      successful therapeutic relationship over the Internet in the absence of nonverbal
      cues. OBJECTIVE: Our objective in this study was to systematically review the
      therapeutic relationship in e-therapy. METHODS: We searched PubMed, PsycINFO, and
      CINAHL through August 2011. Information on study methods and results was
      abstracted independently by the authors using a standardized form. RESULTS: From
      the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic
      relationship. The majority of the reviewed studies were focused on the
      therapeutic alliance-a central element of the therapeutic relationship. Although
      the results do not allow firm conclusions, they indicate that e-therapy seems to
      be at least equivalent to face-to-face therapy in terms of therapeutic alliance,
      and that there is a relationship between the therapeutic alliance and e-therapy
      outcome. CONCLUSIONS: Overall, the current literature on the role of therapeutic
      relationship in e-therapy is scant, and much more research is needed to
      understand the therapeutic relationship in online environments.

PMID- 22858539
TI  - [Statins, diabetes risk and the treatment of hypercholesterolemia in elderly
      people].

PMID- 22858540
TI  - [Is myasthenia gravis overlooked in the over-80s? Two case reports].
AB  - Myasthenia gravis (MG) is diagnosed more often today than previously. The
      increase is mainly found in patients over the age of 60 years. Recent data
      indicate that MG may still be substantially underdiagnosed in very old people. We
      report two cases of MG in elderly women, in whom the initial diagnosis was
      uncertain. When faced with new onset of weakness in an elderly patient,
      particularly of cranial musculature, clinicians should consider MG as a
      diagnostic possibility.

PMID- 22858541
TI  - Electrochemical antioxidant detection technique based on guanine-bonded graphene
      and magnetic nanoparticles composite materials.
AB  - An antioxidant (AO) amperometric technique based on guanine attached to graphene
      and Fe(3)O(4) nanoparticles (NPs) magnetic materials was developed. Guanine
      molecules acted as an antioxidant competitor were bonded with graphene
      nanosheets, onto which magnetic Fe(3)O(4) NPs were attached and the as-prepared
      magnetic composite can be attracted to the electrode surface by an external
      magnetic field. When applied with negative potentials, the dissolved oxygen was
      reduced to H(2)O(2) at the electrode surface, and then reacted with the EDTA
      Fe(ii) complex via a Fenton-like reaction to produce OH radicals. After oxidation
      damage by OH radicals, the electrochemical oxidation of guanine gave a decreased
      current. In the presence of AOs, the reactive oxygen species (ROS, e.g. OH
      radicals and H(2)O(2)) were scavenged by AOs and fewer guanine probe molecules
      were oxidized, thus inducing a higher electrochemical oxidation current of
      guanine. So AOs competed with the guanine probe molecules toward oxidation by
      ROS. The current signals of the guanine probe molecules were proportional to the
      concentrations of AOs. A kinetic model was proposed to quantify the ROS
      scavenging capacities of the AOs. Using guanine as an oxidizable probe and OH
      radicals and H(2)O(2) as endogenous ROS, this kind of AO detection technique
      mimicks the antioxidant protection mechanism by small AO molecules in the human
      body.

PMID- 22858542
TI  - Intrinsic cleavage of receptor-interacting protein kinase-1 by caspase-6.
AB  - Necroptosis is a form of programmed cell death that occurs in the absence of
      caspase activation and depends on the activity of the receptor-interacting
      protein kinases. Inactivation of these kinases by caspase-mediated cleavage has
      been shown to be essential for successful embryonic development, survival and
      activation of certain cell types. The initiator of extrinsic apoptosis, caspase
      8, which has a pro-death as well as a pro-life function, has been assigned this
      role. In the present study we demonstrate that caspase-6, an executioner caspase,
      performs this role during apoptosis induced through the intrinsic pathway. In
      addition, we demonstrate that in the absence of caspase activity, intrinsic
      triggers of apoptosis induce the receptor-interacting-kinase-1-dependent
      production of pro-inflammatory cytokines. We show that ubiquitously expressed
      caspase-6 has a supporting role in apoptosis by cleaving this kinase, thus
      preventing production of inflammatory cytokines as well as inhibiting the
      necroptotic pathway. These findings shed new light on the regulation of
      necroptosis as well as cell death in an inflammatory environment wherein cells
      receive both intrinsic and extrinsic death signals.

PMID- 22858543
TI  - MicroRNAs tune cerebral cortical neurogenesis.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional
      silencing of genes involved in a wide range of developmental and pathological
      processes. It is estimated that most protein-coding genes harbor miRNA
      recognition sequences in their 3' untranslated region and are thus putative
      targets. While functions of miRNAs have been extensively characterized in various
      tissues, their multiple contributions to cerebral cortical development are just
      beginning to be unveiled. This review aims to outline the evidence collected to
      date demonstrating a role for miRNAs in cerebral corticogenesis with a particular
      emphasis on pathways that control the birth and maturation of functional
      excitatory projection neurons.

PMID- 22858544
TI  - Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking
      between plasma membrane and cytoplasm.
AB  - Phosphatidylserine (PS) exposure on the external leaflet of the plasma membrane
      is widely observed during apoptosis and forms the basis for the annexin V binding
      assay to detect apoptotic cell death. Current efforts to explain PS exposure
      focus on two potential mechanisms, activation of a phospholipid scramblase or
      calcium-mediated trafficking of lysosomes to the cell surface. Here, we provide
      evidence that apoptotic PS exposure instead reflects bidirectional trafficking of
      membrane between the cell surface and cytoplasm. Using a series of cell lines,
      some of which expose large amounts of PS during apoptosis and some of which do
      not, we demonstrate that accumulation of plasma membrane-derived cytoplasmic
      vesicles in a dynamin-, clathrin- and Cdc42-independent manner is a previously
      undescribed but widely occurring feature of apoptosis. The apoptotic exposure of
      PS occurs when these vesicles traffic back to cell surface in a calcium-dependent
      process that is deficient in a substantial fraction of human cancer cell lines.
      These observations provide a new model for PS externalization during apoptosis
      and simultaneously identify an altered step that accounts for the paucity of
      apoptotic PS exposure in many cell lines.

PMID- 22858545
TI  - BH3-only protein silencing contributes to acquired resistance to PLX4720 in human
      melanoma.
AB  - B-RAF is mutated to a constitutively active form in 8% of human cancers including
      50% of melanomas. In clinical trials, the RAF inhibitor, PLX4032 (vemurafenib),
      caused partial or complete responses in 48-81% of mutant B-RAF harboring melanoma
      patients. However, the average duration of response was 6-7 months before tumor
      regrowth, indicating the acquisition of resistance to PLX4032. To understand the
      mechanisms of resistance, we developed mutant B-RAF melanoma cells that displayed
      resistance to RAF inhibition through continuous culture with PLX4720 (the tool
      compound for PLX4032). Resistance was associated with a partial reactivation of
      extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, recovery of G1/S
      cell-cycle events, and suppression of the pro-apoptotic B-cell leukemia/lymphoma
      2 (Bcl-2) homology domain 3 (BH3)-only proteins, Bcl-2-interacting mediator of
      cell death-extra large (Bim-EL) and Bcl-2 modifying factor (Bmf). Preventing
      ERK1/2 reactivation with MEK (mitogen-activated protein/extracellular signal
      regulated kinase kinase) inhibitors blocked G1-S cell-cycle progression but
      failed to induce apoptosis or upregulate Bim-EL and Bmf. Treatment with the
      histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid, led to de
      repression of Bim-EL and enhanced cell death in the presence of PLX4720 or
      AZD6244 in resistant cells. These data indicate that acquired resistance to
      PLX4032/4720 likely involves ERK1/2 pathway reactivation as well as ERK1/2
      independent silencing of BH3-only proteins. Furthermore, combined treatment of
      HDAC inhibitors and MEK inhibitors may contribute to overcoming PLX4032
      resistance.

PMID- 22858546
TI  - Optic atrophy 1 mediates mitochondria remodeling and dopaminergic
      neurodegeneration linked to complex I deficiency.
AB  - Mitochondrial complex I dysfunction has long been associated with Parkinson's
      disease (PD). Recent evidence suggests that mitochondrial involvement in PD may
      extend beyond a sole respiratory deficit and also include perturbations in
      mitochondrial fusion/fission or ultrastructure. Whether and how alterations in
      mitochondrial dynamics may relate to the known complex I defects in PD is
      unclear. Optic atrophy 1 (OPA1), a dynamin-related GTPase of the inner
      mitochondrial membrane, participates in mitochondrial fusion and apoptotic
      mitochondrial cristae remodeling. Here we show that complex I inhibition by
      parkinsonian neurotoxins leads to an oxidative-dependent disruption of OPA1
      oligomeric complexes that normally keep mitochondrial cristae junctions tight. As
      a consequence, affected mitochondria exhibit major structural abnormalities,
      including cristae disintegration, loss of matrix density and swelling. These
      changes are not accompanied by mitochondrial fission but a mobilization of
      cytochrome c from cristae to intermembrane space, thereby lowering the threshold
      for activation of mitochondria-dependent apoptosis by cell death agonists in
      compromised neurons. All these pathogenic changes, including mitochondrial
      structural remodeling and dopaminergic neurodegeneration, are abrogated by OPA1
      overexpression, both in vitro and in vivo. Our results identify OPA1 as molecular
      link between complex I deficiency and alterations in mitochondrial dynamics
      machinery and point to OPA1 as a novel therapeutic target for complex I
      cytopathies, such as PD.

PMID- 22858547
TI  - Genotypes and antimicrobial profiles of Shigella sonnei isolates from diarrheal
      patients circulating in Beijing between 2002 and 2007.
AB  - Shigella sonnei has become the dominant serotype causing shigellosis in Asian
      countries in recent years. In this study, we characterize the increasing trend of
      antibiotic resistance profiles and genotypes of S. sonnei isolates in the Beijing
      area. From January 2002 to December 2007, a total of 1108 Shigella isolates
      including 362 S. sonnei were recovered from diarrhea patients at the 302nd
      Hospital in Beijing. While the frequency of S. flexneri gradually decreased, S.
      sonnei gradually increased and became the dominant species. A total of 362 S.
      sonnei isolates were further analyzed for their antimicrobial profiles and 272
      revived isolates were selected for genotyping analysis, respectively. High-level
      antimicrobial resistances were observed in sulfamethoxazole/trimethoprim (94.5%),
      ampicillin (40.3%), piperacillin (36.5%), and ceftriaxone (12.8%) with
      significant single- and multiple-drug resistance increase trends from 2002 to
      2007 (P = 0.0000). Pulsed-field gel electrophoresis analysis indicated that 263
      (96.7%) S. sonnei belonged to 1 clonal genotype A, which were further divided
      into A1-A6 subtypes. While subtype A2 was dominant in the early stage of study
      years, subtype A4 started to emerge and increased significantly in later years.
      Antimicrobial resistance rates are statistically different among the 6 subtypes
      (P = 0.0000), and A4 possessed the highest resistance rates to ampicillin (83.7%)
      and piperacillin (81.4%). Subtype A3 was highly clustered in inpatients compared
      to other subtypes (P = 0.0145). This study indicates that a clonal S. sonnei
      strain has become dominant in the Beijing area, and subtype A4 is responsible for
      increased antibiotic resistance.

PMID- 22858548
TI  - Emergence of a novel Shigella flexneri serotype 1d in China.
AB  - We report on the isolation of 5 Shigella flexneri strains displaying a novel
      serotype, 1d, that shares serologic features from both S. flexneri serotypes 1a
      and X. The 1d strains contained serotype-converting bacteriophages SfI and SfX in
      tandem on the chromosome. These strains were likely originated from serotype X
      strains through SfI infection.

PMID- 22858549
TI  - Are epidemiologic cut-off values predictors of the in vivo efficacy of azoles in
      experimental aspergillosis?
AB  - We tried to correlate the in vitro activity and the in vivo efficacy of
      voriconazole (VRC) and posaconazole (POS) against Aspergillus flavus and
      Aspergillus niger. The in vitro susceptibility of a large set of isolates was
      determined by broth microdilution and disk diffusion methods, while the in vivo
      efficacy was assessed in a murine model of disseminated infection. For A. flavus,
      VRC showed efficacy even for strains with MICs above the epidemiologic cutoff
      value (ECV) (1 MUg/mL). For A. niger, VRC was ineffective against those strains
      for which the MIC was 1 dilution below the corresponding ECV (2 MUg/mL). POS
      showed efficacy against all the strains of both species included in the study,
      although isolates with MICs > ECV were not tested.

PMID- 22858551
TI  - Reprint of: The second step in resuscitation-the treatment of the post
      resuscitation disease.

PMID- 22858550
TI  - Subthalamic nucleus activity optimizes maximal effort motor responses in
      Parkinson's disease.
AB  - The neural substrates that enable individuals to achieve their fastest and
      strongest motor responses have long been enigmatic. Importantly, characterization
      of such activities may inform novel therapeutic strategies for patients with
      hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the
      basal ganglia may play an important role, not only in the attainment of maximal
      motor responses under standard conditions but also in the setting of the
      performance enhancements known to be engendered by delivery of intense stimuli.
      To this end, we recorded local field potentials from deep brain stimulation
      electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with
      Parkinson's disease, as they executed their fastest and strongest handgrips in
      response to a visual cue, which was accompanied by a brief 96-dB auditory tone on
      random trials. We identified a striking correlation between both theta/alpha (5
      12 Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and
      force measures, which explained close to 70% of interindividual variance in
      maximal motor responses to the visual cue alone, when patients were ON their
      usual dopaminergic medication. Loud auditory stimuli were found to enhance
      reaction time and peak rate of development of force still further, independent of
      whether patients were ON or OFF l-DOPA, and were associated with increases in
      subthalamic nucleus power over a broad gamma range. However, the contribution of
      this broad gamma activity to the performance enhancements observed was only
      modest (<=13%). The results implicate frequency-specific subthalamic nucleus
      activities as substantial factors in optimizing an individual's peak motor
      responses at maximal effort of will, but much less so in the performance
      increments engendered by intense auditory stimuli.

PMID- 22858552
TI  - Wide variability in drug use in out-of-hospital cardiac arrest: a report from the
      resuscitation outcomes consortium.
AB  - BACKGROUND: Despite the publication and dissemination of the Advanced Cardiac
      Life Support guidelines, variability in the use of drugs during resuscitation
      from out-of-hospital cardiac arrest may exist between different Emergency Medical
      Services throughout North America. The purpose of this study was to characterize
      the use of such drugs and evaluate their relationship to cardiac arrest outcomes.
      METHODS AND RESULTS: The Resuscitation Outcomes Consortium Registry-Cardiac
      Arrest collects out-of-hospital cardiac arrest data from 264 Emergency Medical
      Services agencies in 11 geographical locations in the U.S. and Canada.
      Multivariable logistic regression was used to assess the association between drug
      use, characteristics of the cardiac arrest and a pulse at emergency department
      arrival and survival to discharge. A total of 16,221 out-of-hospital cardiac
      arrests were attended by 74 Emergency Medical Services agencies. There was a
      considerable variability in the administration of amiodarone and lidocaine for
      the treatment of shock resistant ventricular tachycardia/ventricular
      fibrillation. For non-shockable rhythms, atropine use ranged from 29 to 95% and
      sodium bicarbonate use ranged from 0.2 to 73% across agencies in the 89% of
      agencies that used the drug. Epinephrine use ranged from 57 to 98% within
      agencies. Neither lidocaine nor amiodarone was associated with a survival benefit
      while there was an inverse relationship between the administration of
      epinephrine, atropine and sodium bicarbonate and survival to hospital discharge.
      CONCLUSIONS: There is considerable variability among Emergency Medical Services
      agencies in their use of pharmacological therapy for out-of-hospital cardiac
      arrests which may be resolved by performing large randomized trials examining
      effects on survival.

PMID- 22858553
TI  - Hormesis: protecting neurons against cellular stress in Parkinson disease.
AB  - Protein folding stress is a salient feature of the most frequent
      neurodegenerative diseases. Although the accumulation of abnormally folded
      proteins is a well-characterized event underlying the pathology, the way cells
      respond to this phenomenon is not well understood. Signs of endoplasmic reticulum
      (ER) stress are a common marker of neurodegeneration in many diseases, which may
      represent two contrasting processes: cell protection events due to activation of
      adaptive programs, or a chronic stress state that culminates in apoptosis to
      eliminate irreversibly injured cells. Autophagy has been proposed as a protective
      mechanism to overcome neurodegeneration that is also modulated by ER stress. In
      this issue of autophagy Bertrand Mollereau's group provides novel evidence
      indicating that engagement of nonharmful levels of ER stress protects against
      experimental Parkinson disease. At the mechanistic level, a homeostatic crosstalk
      between ER stress signaling and the autophagy pathway was proposed to mediate the
      therapeutic effects. This study, together with recent findings, supports the
      involvement of a "hormesis mechanism" to handle degeneration through
      preconditioning mediated by a dynamic balance between ER stress and autophagy.
      The implications for aging and future therapeutic development are discussed.

PMID- 22858554
TI  - Moderators of the internalization-body dissatisfaction relationship in middle
      school girls.
AB  - The purpose of the present study was to replicate and extend previous research by
      examining the moderating effects of self-esteem, physical self-concept, physical
      appearance comparisons, BMI, pubertal status, and cardiorespiratory fitness, on
      the internalization-body dissatisfaction relationship in middle school girls.
      Hierarchical multiple regression (HMR) was used to examine direct and moderating
      effects of these variables. Internalization was related directly and
      significantly to body dissatisfaction, as were the proposed moderators (i.e.,
      self-esteem, physical self-concept, physical appearance comparisons, BMI,
      pubertal status, and cardiorespiratory fitness); however, these variables failed
      to significantly influence the internalization-body dissatisfaction relationship.
      Possible explanations for the lack of moderating effects and directions for
      future research are discussed.

PMID- 22858555
TI  - Cost-effectiveness of hepatitis A vaccination for adults in Belgium.
AB  - Hepatitis A vaccination targeting adults (or adult risk-groups like e.g.
      travellers, health care workers, soldiers or teachers) could be considered an
      alternative to a universal infant or adolescent vaccination program in low
      endemic countries. We estimated the current disease burden of hepatitis A in
      Belgium, and evaluated whether adult vaccination is cost-effective. We used a
      Markov cohort model to simulate the costs and effects of (1) vaccination of
      adults and (2) serological screening of adults and vaccination of susceptibles
      and compared these with the current situation. The results indicated that these
      expanded vaccination strategies are not cost-effective in the epidemiological
      circumstances of a typical low-endemic western country. In order to gain 1
      quality-adjusted life year the health care payer would have to pay 185,000? for
      vaccination and 223,000? for screening and vaccination of seronegatives. For
      adult vaccination to be cost-effective, risk-groups would need to be exposed to a
      force of infection that is 3.5-4 times higher than currently estimated in the
      general population; or the total costs of vaccination would have to drop with
      approximately 75%.

PMID- 22858556
TI  - Maternal knowledge, attitudes and beliefs regarding gastroenteritis and rotavirus
      vaccine before implementing vaccination program: which key messages in light of a
      new immunization program?
AB  - In July 2010, the National Advisory Committee on Immunization (NACI) recommended
      the systematic administration of rotavirus vaccines for all infants in Canada.
      According to the Erickson and De Wals framework, multiple factors need to be
      evaluated before implementing such a decision, including the study of the
      acceptability of this vaccine by the general population. A cross-sectional survey
      was conducted from February 10 to February 18, 2011, at the Sherbrooke University
      Hospital Center in the province of Quebec. A questionnaire, based upon the Health
      Belief Model (HBM) and theoretical planned action, was self-administered to
      pregnant or early post-partum women. The variables collected included socio
      demographic data, past experience with gastroenteritis, cues to vaccination and
      HBM dimensions. The associations between questionnaire variables and vaccination
      intention were assessed using univariate and multivariate analyses. Of the 343
      respondents, only 29% had already heard about rotavirus vaccination and among
      these, the intention of vaccination was 74%. In multivariate analysis, having a
      perception of infant vulnerability to gastroenteritis (OR=2.3, 95% CI 1.3-4.0)
      and having no other child at home (OR=2.3, 95% CI 1.3-4.2) were factors
      positively associated with a higher intention of vaccination, contrary to having
      already heard about the rotavirus vaccine in the media (OR=0.5, 95% CI 0.2-0.9).
      The three cues independently associated with intention of vaccination were the
      reimbursement of the vaccine (OR=3.0, 95% CI 1.6-5.7), its recommendation by a
      doctor (OR=21.2, 95% CI 5.8-75.9) and its protection against the most severe
      forms of gastroenteritis (OR=4.4, 95% CI 1.4-13.6). To improve the success of
      this new vaccination program, several key messages should be integrated in the
      information made available to the general population: (1) rotavirus
      gastroenteritis is a mandatory infection for every child <5 years; (2) the
      vaccine is reimbursed and included in the provincial vaccination program; and (3)
      the vaccine protects against the worst forms of gastroenteritis. Finally, support
      should be offered to physicians as they play a key role in public acceptance of
      new vaccines.

PMID- 22858557
TI  - Cross-reactive gut-directed immune response against Salmonella enterica serovar
      Paratyphi A and B in typhoid fever and after oral Ty21a typhoid vaccination.
AB  - BACKGROUND: There are no vaccines against paratyphoid fever in clinical use. The
      disease has become more wide-spread and there is a growing problem of antibiotic
      resistance among the strains. Previous reports suggest that the oral live
      Salmonella Typhi Ty21a-vaccine confers protection against paratyphoid B fever.
      Data on efficacy against paratyphoid A fever are somewhat contentious. The
      present study investigated the immunological basis for such efficacy reports at a
      single-cell level: plasmablasts (identified as antibody-secreting cells, ASC)
      were studied for secretion of antibodies cross-reactive with Salmonella Paratyphi
      in the circulation of patients with enteric fever and of volunteers vaccinated
      with Ty21a. MATERIALS AND METHODS: Thirty volunteers immunized with Ty21a and
      five patients with enteric fever were investigated for Salmonella Typhi and
      Salmonella Paratyphi A/B/C-specific circulating plasmablasts. PBMC were sorted by
      their expression of homing receptors (HR) for the intestine (alpha4beta7),
      peripheral lymph node (l-selectin) and skin (CLA) and typhoid- and paratyphoid
      specific plasmablasts were enumerated with ELISPOT. RESULTS: Before vaccination,
      no cross-reactive ASC were found in the volunteers. In addition to the Salmonella
      Typhi-specific response, a significant cross-reactive immune response was mounted
      against Salmonella Paratyphi A and B both in the patients and the vaccinees. The
      magnitude of the response increased in the order Salmonella Paratyphi A (median
      30 ASC/10(6) PBMC)->Salmonella Paratyphi B (median 81)->Salmonella Typhi (median
      301) in the vaccinees. Both in patients and in vaccinees, the homing receptor
      (HR) selection favored homing to the gut, indicating a humoral intestinal immune
      response. CONCLUSIONS: These immunological data provide evidence consistent with
      previous reports describing certain levels of cross-protective efficacy of Ty21a
      against paratyphoid fever. Controlled studies are needed to evaluate cross
      protective efficacy. In the current situation where paratyphoid fever is emerging
      and no vaccines are available, any level of cross-protective capacity is
      valuable.

PMID- 22858558
TI  - Hypertension as a potential biomarker of efficacy in patients with
      gastrointestinal stromal tumor treated with sunitinib.
AB  - BACKGROUND: Reliable biomarkers of sunitinib response in gastrointestinal stromal
      tumor (GIST) are lacking. Hypertension (HTN), an on-target class effect of
      vascular endothelial growth factor signaling-pathway inhibitors, has been shown
      to correlate with clinical outcome in advanced renal cell carcinoma treated with
      sunitinib. PATIENTS AND METHODS: This retrospective analysis examined
      correlations between sunitinib-associated HTN and antitumor efficacy (N = 319)
      and safety (N = 1565) across three advanced GIST studies. Blood pressure (BP) was
      measured on days 1 and 28 of each treatment cycle at a minimum. Time-to-event
      endpoints were estimated using Kaplan-Meier methods, and patient subgroups with
      and without HTN (maximum systolic BP >= 140 mmHg and/or diastolic BP >= 90 mmHg)
      were compared using Cox proportional hazards models. Landmark analyses evaluated
      associations between early HTN and efficacy endpoints. Adverse events (AEs) were
      compared between groups. RESULTS: Sunitinib-associated HTN correlated with
      improved objective response rates, time to tumor progression, progression-free
      survival, and overall survival. Almost all benefits remained significant in
      multivariate and landmark analyses. Overall incidences of HTN-related AEs were
      low and similar between groups; incidences of cardiovascular AEs were somewhat
      higher in patients with HTN. CONCLUSION: Sunitinib-associated HTN appeared to
      correlate with improved clinical outcomes in GIST, while incidences of HTN
      associated AEs were generally low and manageable.

PMID- 22858559
TI  - Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy
      in extensive-disease-small-cell lung cancer: results from a randomized, double
      blind, multicenter phase 2 trial.
AB  - BACKGROUND: Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival
      benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by
      the protocol-defined guidelines. This phase 2 study evaluated
      ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung
      cancer (ED-SCLC). DESIGN: Patients (n=130) with chemotherapy-naive ED-SCLC were
      randomized 1: 1: 1 to receive paclitaxel (175 mg/m2)/carboplatin (area under the
      curve=6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative
      regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin followed by
      placebo+paclitaxel/carboplatin) or phased ipilimumab
      (placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin).
      Treatment was administered every 3 weeks for a maximum of 18 weeks (induction),
      followed by maintenance ipilimumab or placebo every 12 weeks. End points included
      progression-free survival (PFS), irPFS, best overall response rate (BORR);
      irBORR, overall survival (OS), and safety. RESULTS: Phased ipilimumab, but not
      concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio)=0.64;
      P=0.03]. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75; P=0.13)
      occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively,
      were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2,
      3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade
      3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and
      control, respectively. CONCLUSION: These results suggest further investigation of
      ipilimumab in ED-SCLC.

PMID- 22858560
TI  - Evaluation of different moxibustion doses for lumbar disc herniation: multicentre
      randomised controlled trial of heat-sensitive moxibustion therapy.
AB  - BACKGROUND: There is some evidence for the effectiveness of moxibustion for the
      treatment of lumbar disc herniation (LDH), but it remains unclear what dose is
      optimal. OBJECTIVE: To compare the effectiveness of a new technique of
      individualised 'sensitivity elimination' dose versus a standardised 15 min dose
      in the treatment of LDH. METHODS: This study was a multicentre (four centres in
      China), randomised, controlled trial with two parallel arms (group A,
      individualised sensitivity elimination dose; group B, standardised dose). The
      most heat-sensitised acupuncture point from the triangle bound by BL25 and GV2
      was selected. Both groups received 18 sessions over 2 weeks. The outcome was
      evaluated by Modified Japanese Orthopaedic Association scale (M-JOA) score before
      and after treatment and at 6-month follow-up examination. All main analyses were
      by intention to treat. RESULTS: A total of 96 patients were included. A
      significant difference of total M-JOA score was noted between the groups at weeks
      1 and 2 (p<0.05). Significant differences were also evident during the follow-up
      period (p<0.01). The mean duration of moxibustion was 42.7+/-5.4 (range, 22-58)
      minutes in the experimental group. CONCLUSIONS: The effectiveness of the
      individualised sensitivity elimination dose appears superior to the standardised
      dose in the treatment of LDH. Only 15 min moxibustion in the conventional dose
      group seemed insufficient to elicit the satisfactory clinical effects obtained by
      heat-sensitive moxibustion therapy. However, in view of some limitations of this
      study further research is necessary before this can be stated conclusively. TRIAL
      REGISTRATION: Controlled Clinical Trials: ChiCTR-TRC-09000602.

PMID- 22858561
TI  - Subendocardial dysfunction in patients with chronic severe aortic regurgitation
      and preserved ejection fraction detected with speckle-tracking strain imaging and
      transmural myocardial strain profile.
AB  - AIMS: It remains difficult to detect subtle left ventricular (LV) myocardial
      dysfunction in chronic aortic regurgitation (AR) patients with the preserved
      ejection fraction (EF). METHODS AND RESULTS: We studied 36 chronic severe AR
      patients undergoing surgical correction with the EF of 58 +/- 6% (all >= 50%).
      Echocardiography was performed before and 12 +/- 8 months after surgical
      correction. We used two-dimensional speckle-tracking strain imaging to evaluate
      global radial strain in the inner-half (GRSinner), outer-half (GRSouter), and
      total (GRStotal) layer from the mid-LV short-axis view. We also evaluated the
      transmural strain profile in the LV posterior wall by using myocardial tissue
      Doppler radial strain, and the location of peak strain was determined as the
      percentage of the distance from the endocardium to the epicardium accounted for
      by the wall thickness. Fifteen EF-matched normal volunteers were studied for
      comparison. GRSinner for AR patients was significantly smaller than that for
      controls (28.9 +/- 12.9 vs. 37.1 +/- 9.1%, P = 0.032), and the location of peak
      strain had significantly shifted to the epicardial side compared with that in
      controls (27.1 +/- 14.0-13.2 +/- 4.8%, P = 0.001). In contrast, GRStotal and
      GRSouter were similar for the two groups. After surgical correction, EF increased
      from 58 +/- 6 to 62 +/- 7% (P = 0.018), GRSinner from 27.8 +/- 12.5 to 37.7 +/-
      14.6% (P < 0.0001), and the location of peak strain significantly shifted to the
      endocardial side (26.9 +/- 13.9-19.1 +/- 11.9%, P = 0.028). However, GRStotal and
      GRSouter did not change. CONCLUSION: The LV endocardium side, impaired in chronic
      AR patients with the preserved EF, improved after surgical correction. Our
      observations may prove useful for evaluating subtle early changes in such
      patients.

PMID- 22858562
TI  - Imaging of coronary artery plaques using contrast-enhanced optical coherence
      tomography.

PMID- 22858563
TI  - [Reflections on group activity in primary care].

PMID- 22858564
TI  - [Vitamin D supplements in childhood].

PMID- 22858565
TI  - AMOR II: an effort to eradicate psychosocial barriers induced by immigration
      phenomenon in children with cancer.
AB  - BACKGROUND: Immigration in the childhood cancer population constitutes a stressor
      factor because of high biopsychosocial vulnerability. In recent years the
      incidence of immigrant children in our unit has increased. Since 2005 we have
      developed a psychosocial program to overcome this challenge. Our objective is to
      assess its impact on the immigrant pediatric population. PROCEDURE: We have
      compared new cases (n=114) from 2005 to 2010 with historical cases (n=95) from
      1995 to 2004. We administered a long-term follow-up questionnaire allowing for
      the assessment of symptoms associated with biopsychosocial variables. RESULTS:
      Most of our immigrant patients came from Latin America and we observed a
      significant increase of cases coming from Morocco and Romania. The most common
      diagnosis was hematological malignancies. From 2005 to 2010 the disease status
      was mainly initial, whereas in the period 1995 to 2004 most of the patients
      arrived with advanced disease. Socioeconomic variables amongst these patients
      tended towards low incomes, high unemployment, and economic difficulties. The
      implementation of the biopsychosocial protocol AMOR II improved adaptation
      (P=0.012), the amount and understanding of information received (P=0.002), and
      family emotional support (P=0.004). CONCLUSIONS: In brief, our biopsychosocial
      protocol had significantly increased some psychosocial variables. However,
      immigration in Spain is still associated with economic difficulties, "aculturism"
      and failure to adapt.

PMID- 22858566
TI  - Clear cell sarcoma of the jaw: a case report and review of the literature.
AB  - Clear cell sarcoma (CSS) is a unique malignant soft tissue tumor that mainly
      occurs from the aponeurotic tissue and tendons of extremities. It is rare in the
      pediatric population. The tumor does not respond well to chemotherapy or
      irradiation. Complete surgical resection offers the best chance for a cure. Most
      studies have demonstrated poor prognosis of this tumor, if it is >5 cm. The
      literature suggests that local recurrence and distant metastasis are not uncommon
      even with wide resection and that late recurrence and metastasis commonly occur.
      This case report discusses CSS in the jaw of a pediatric patient. To our
      knowledge, this is the only case of CSS of the jaw. 

PMID- 22858567
TI  - Granulocyte transfusion therapy in pediatric patients after hematopoietic stem
      cell transplantation:  a 5-year single tertiary care center experience.
AB  - BACKGROUND: Granulocyte transfusion (GTx) has been used in neutropenic patients
      to treat infections; however, there are few studies that document its efficacy,
      especially in pediatric patients after hematopoietic stem cell transplantation
      (HSCT). We, therefore, reviewed the use of GTx in these patients. MATERIALS AND
      METHODS: A retrospective observational analysis was performed on all pediatric
      HSCT patients between January 2005 and January 2010 who met our institution's
      criteria for GTx and received more than 1 GTx. Unstimulated granulocyte donors
      were used until June 2007, followed by dexamethasone-stimulated donors
      thereafter. Outcomes were infection clearance, safety profile of GTx, and 30-day
      survival. RESULTS: One hundred fifty-three GTxs were administered to 16 pediatric
      HSCT patients. Indications for GTx: bacterial (69%), fungal (19%), and combined
      infection (12%). Concurrent infections, mostly bacterial, developed in 60%
      patients. One adverse reaction (pulmonary toxicity) was reported. The absolute
      neutrophil count of the stimulated products was significantly higher compared
      with the unstimulated products; however, neither the average number of
      granulocytes transfused by weight nor outcomes difference was noticed between
      these groups. CONCLUSIONS: GTx is safe in neutropenic and infected pediatric
      patients after HSCT. However, no difference in the outcomes was noticed between
      the group that received stimulated products and the group that received
      unstimulated products.

PMID- 22858568
TI  - Central diabetes insipidus:  an unusual complication in a child with juvenile
      myelomonocytic leukemia and monosomy 7.
AB  - Central diabetes insipidus (DI) is well-documented as a presenting feature of
      myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is
      unusual in pediatric patients with myeloid malignancies. We report here this rare
      complication in a child with neurofibromatosis type 1 who developed juvenile
      myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of
      DI arising as a complication in myeloid malignancies demonstrate a close
      association with deletion of chromosome 7. The clinical characteristics and
      outcomes of these uncommon cases in children are reviewed and discussed.

PMID- 22858569
TI  - Diagnostic paracentesis in an acute lymphoblastic leukemia child without
      characteristic symptoms of pancreatitis.

PMID- 22858570
TI  - Videos on rhabdomyosarcoma on YouTube: an example of the availability of
      information on pediatric tumors on the web.
AB  - PURPOSE: Video-sharing sites have become increasingly important in recent years
      in providing information and orienting people's decisions relating to their
      health. Adolescents and their families use internet to obtain information on
      pediatric oncological diseases. METHODS: We describe the availability and type of
      video content and origin on YouTube relating to a particular set of pediatric
      neoplastic diseases, that is, rhabdomyosarcoma and soft-tissue sarcoma. RESULTS:
      A total of 149 videos were analyzed: 25 were considered as useful; only 1 video
      was produced by a doctor, whereas 82.5% were produced by patients or their
      families, in many cases for commemorating the death of a child. CONCLUSIONS: Our
      observations indicate that video-sharing sites have become tools, such as blogs
      and social media, that make it easier for patients to describe their impressions
      and experiences of the disease, and this could help other patients devise
      strategies for coping with the disease, providing them with support and
      opportunities for sharing information and resources.

PMID- 22858571
TI  - Survivin gene promoter -31 G/C polymorphism is associated with Wilms tumor
      susceptibility in Serbian children.
AB  - Survivin, an apoptotic inhibitor, is overexpressed in various types of cancer.
      Mechanisms of survivin upregulation are still poorly understood, but single
      nucleotide polymorphisms in the survivin gene promoter have been shown to
      modulate survivin expression and consequently the risk for some types of cancer.
      The aim of the present study was to investigate whether survivin promoter -31 G/C
      and -241 C/T polymorphisms could represent susceptibility factors for Wilms tumor
      (WT) development in Serbian population. Genotype and allele frequencies for the 2
      polymorphisms in survivin promoter have been analyzed by polymerase chain
      reaction/restriction fragment length polymorphism in 59 WT patients and 82
      controls. The frequencies of alleles and genotypes were significantly different
      between patients and controls for the -31 G/C polymorphism. Individuals with CC
      and CG genotypes had significantly decreased risk of WT compared with GG
      individuals (odds ratio 0.26, 95% confidence interval, 0.07-0.96; odds ratio
      0.30, 95% confidence interval, 0.15-0.60). There was also a statistically
      significant difference in genotype frequencies between intermediate and high-risk
      prognostic groups (P=0.015). The -241 C/T polymorphism did not show association
      with WT susceptibility. Our findings suggest that the G allele at -31 survivin
      gene promoter position is associated with a significantly higher cancer risk in
      Serbian children, with a gene dosage effect.

PMID- 22858572
TI  - Early mortality in children with advanced mature B-cell malignancies in a middle
      income country.
AB  - Scant information about the early toxicity of high-dose chemotherapy regimens for
      the treatment of mature B-cell malignancies (B-non-Hodgkin lymphoma) in
      developing countries is available, so we performed a retrospective evaluation of
      children with B-non-Hodgkin lymphoma treated with Berlin-Frankfurt-Muenster-based
      protocols in Argentina (1993 to 2007). In the second protocol, induction
      chemotherapy was modified introducing high-dose cytarabine and etoposide (block
      CC) instead of high-dose methotrexate (block AA). Forty-one patients with stage
      III and elevated lactate dehydrogenase or stage IV or B-acute lymphoblastic
      leukemia were included. Five patients (12.1%) had an early death at a median of
      23 days after treatment initiation, caused by sepsis in 4 and by a Stevens
      Johnson syndrome in 1. Children that had an early death were significantly more
      likely to present with renal failure (P=0.04) and have significantly higher
      levels of phosphate and creatinine on admission (P=0.02 and 0.008). Eighty
      percent of children dying early had prior extensive abdominal surgery and
      positive blood cultures after the first cycle. Induction with AA block was
      associated with a higher frequency of severe orointestinal toxicity (P=0.04). We
      conclude that renal failure was associated to increased risk of mortality leading
      to a higher risk of sepsis, especially in patients that underwent abdominal
      surgery.

PMID- 22858573
TI  - Laparoscopic-facilitated endoscopic submucosal dissection, mucosal resection, and
      partial circumferential ("wedge") colon wall resection for benign colorectal
      neoplasms that come to surgery.
AB  - BACKGROUND: Large polyps that come to surgery are removed via colectomy (CR).
      Alternatives are MIS-facilitated endoscopic submucosal dissection/endoscopic
      mucosal resection (ESD/EMR) or wedge resection (WR). This study presents the
      results of 26 polyp patients who had minimally invasive surgery (MIS)-monitored
      ESD/EMR, WR, or if necessary, standard CR. METHODS: The authors used a
      retrospective review of 1 surgeon's experience. ESD/EMR was the first choice, WR
      was the second, and CR was the last resort. RESULTS: Polyp locations were as
      follows: right/transverse, 16 (62%); rectum, 7 (27%); and left/sigmoid, 3 (12%).
      ESD/EMR was successful in 13 patients and WR in 4; 9 patients required CR. Median
      flatus times were as follows: ESD/EMR, 1 day; WR, 2 days; and CR, 3 days (ESD/EMR
      vs CR, P = .01). Median length of stay was as follows: ESD/EMR, 3 days; WR, 5
      days; and CR, 5 days (ESD/EMR vs CR, P = .0037). There were no leaks or
      abscesses. Carcinoma was found in 3 patients. Postoperatively, 2 ESD/EMR patients
      had residual polyp fully removed via a scope. CONCLUSIONS: ESD/EMR and WR appear
      to be safe but techniques are evolving. Larger studies are needed.

PMID- 22858574
TI  - Specialized instrumentation facilitates stable peritoneal access, gastric
      decompression, and visualization during transgastric endoscopic peritoneoscopy.
AB  - PURPOSE: The lack of high-fidelity instrumentation has impeded the development
      and implementation of natural orifice transluminal endoscopic surgery (NOTES). A
      steerable flexible trocar (SFT), a rotary access needle (RAN), and an
      articulating needle knife were developed as components of a flexible instrument
      set to facilitate transgastric peritoneal access and transluminal abdominal
      procedures. This cohort study aimed to assess the safety, feasibility, and
      efficacy of these devices during transgastric peritoneoscopy. METHODS: Ten
      morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass
      participated in the study. Following laparoscopic access, transgastric peritoneal
      access was established using the SFT and RAN, and transgastric peritoneoscopy
      performed. NOTES adhesiolysis was performed in 2 patients with significant intra
      abdominal adhesions due to prior surgery. Outcome measures included time to enter
      the peritoneal cavity, ability to visualize each quadrant of the abdomen, ability
      to perform adhesiolysis, and complications. RESULTS: Ten patients with a median
      body mass index as stated in table 1 of 47.5 kg/m(2) were enrolled. Successful
      transgastric access was achieved in 8 of the 10 patients. One procedure was
      aborted because of difficulty creating the gastrotomy. Another procedure was
      aborted because of the difficult passage of the device through the oropharynx. An
      upper esophageal laceration occurred in one patient. Transgastric peritoneal
      access required 17.4 +/- 5.5 minutes, and peritoneoscopy averaged 24.7 +/- 7.6
      minutes. The 4 abdominal quadrants were visualized and were accessible with the
      endoscope in all patients. CONCLUSIONS: The SFT and RAN facilitate transgastric
      peritoneal access and visualization of difficult-to-reach areas of the
      peritoneum. These devices provide advanced instrumentation for transgastric NOTES
      procedures; however, care must be taken during the transoral insertion to avoid
      complications.

PMID- 22858575
TI  - Safety and application of transumbilical single-incision laparoscopic gastrectomy
      for GIST: SILS in benign gastric disease.
AB  - BACKGROUND: The authors report a new technique of umbilical single-incision
      laparoscopic surgery (SILS) in the treatment of gastrointestinal stromal tumors
      (GISTs) of the stomach using conventional laparoscopic instruments. METHODS:
      Preliminary experience with umbilical SILS operation in 13 patients with GIST was
      introduced. RESULTS: Umbilical SILS operation for GISTs was feasible with
      conventional laparoscopic instruments. No intraoperative or postoperative
      complications, such as secondary hemorrhage, anastomotic leakage, or obstruction,
      were recorded. The patients fully recovered and the single umbilical scar healed
      well. CONCLUSION: SILS for GISTs is a feasible and safe technique when performed
      by experienced laparoscopic surgeons. With advanced surgical technology and
      technique, truly minimally invasive surgical procedures, such as SILS, are
      feasible.

PMID- 22858576
TI  - Diagnostic testing and the average absolute likelihood ratio: application to
      diagnosing wide QRS complex tachycardia and other ED diseases.
AB  - The Bayesian approach to disease diagnosis in the emergency department is
      facilitated by the use of likelihood ratios (LRs) to evaluate diagnostic tests.
      The use of dichotomous, interval, and joint LRs for single and multiple tests is
      reviewed, and comparison is made to regression modeling. The clinical motivation
      for a single statistic to describe the average change in the odds of disease
      associated with the use of a particular test or series of tests is described.
      This new extension of the LR concept is termed the average absolute LR (AALR).
      Illustrative examples include the use of elevated electrocardiogram ST segment
      and troponin to diagnose acute myocardial infarction, and serum D-dimer and
      computed tomographic angiography to diagnose pulmonary embolism. Finally, a
      detailed example with original data demonstrating the use of the AALR to compare
      QRS duration, QRS axis, and the 2 tests combined to diagnose ventricular
      tachycardia in patients with stable sustained regular wide QRS tachycardia is
      provided. Application of both tests together to patients with wide QRS complex
      tachycardia changes the odds of ventricular tachycardia, on average, by a factor
      of 3.5 (95% confidence interval, 2.4-6.2). Challenges are described, and methods
      are provided to estimate the 95% confidence interval of the LR and AALR using
      bootstrapping techniques. The AALR is a test statistic that may be helpful for
      clinicians and researchers in evaluating and comparing diagnostic testing
      approaches.

PMID- 22858577
TI  - Radiosynthesis of [11C]SNAP-7941--the first PET-tracer for the melanin
      concentrating hormone receptor 1 (MCHR1).
AB  - The melanin concentrating hormone (MCH) system is a new target to treat human
      disorders. Our aim was the preparation of the first PET-tracer for the MCHR1.
      [(11)C]SNAP-7941 is a carbon-11 labeled analog of the published MCHR1 antagonist
      SNAP-7941. The optimum reaction conditions were 2 min reaction time, <=25 degrees
      C reaction temperature, and 2 mg/mL precursor (SNAP-acid) in acetonitrile, using
      [(11)C]CH(3)OTf as methylation agent. [(11)C]SNAP-7941 was prepared in a reliable
      and feasible manner with high radiochemical yields (2.9+/-1.6 GBq; 11.5+/-6.4%
      EOB, n=15).

PMID- 22858578
TI  - Measurement of fission cross section for 232Th(n,x)89Rb reaction induced by
      neutrons around 14 MeV.
AB  - In order to investigate the fission process in more detail, and to compare with
      the measurement of cumulative fission yields, the fission cross section of the
      (232)Th(n,x)(89)Rb reaction induced by 14 MeV neutron was measured using the
      activation technique. In our measurement the neutron flux was determined using
      the monitor (27)Al(n,alpha)(24)Na reaction, and the neutron energies were
      measured by the method of cross-section ratios of (90)Zr(n,2n)(89)Zr to
      (93)Nb(n,2n)(92m)Nb reactions. The cross sections were deduced as 14.0+/-0.9 mb
      at E(n)=14.7+/-0.3 MeV and 13.2+/-1.0 mb at E(n)=14.1+/-0.3 MeV.

PMID- 22858579
TI  - Aesculin inhibits matrix metalloproteinase-9 expression via p38 mitogen activated
      protein kinase and activator protein 1 in lipopolysachride-induced RAW264.7
      cells.
AB  - Expression of matrix metalloproteinase 9 (MMP-9) may contribute to inflammatory
      conditions such as arthritis, hepatitis, atherosclerosis, and pulmonary fibrosis,
      which involves the destruction of the extracellular matrix (ECM). Macrophages
      stimulated with lipopolysaccharide (LPS) express MMP-9 through the nuclear factor
      kappa B (NF-kappaB) and activator protein 1 (AP-1) signaling pathways. Aesculin,
      a 6,7-dihydroxycoumarin-6-O-beta-glucopyranoside, has been highlighted for its
      anti-hepatotoxic, hypouricemic, antioxidative, photo-protective, and anti
      apoptotic properties. In this study, we investigated the effects of aesculin on
      LPS-stimulated MMP-9 production and its regulatory mechanism by using murine
      macrophage RAW264.7 cells. Aesculin did not trigger any significant cytotoxic
      effect on RAW264.7 cells at concentration up to 150 MUM. Secretion and expression
      levels of MMP-9, which were highly elevated by LPS treatment, were reduced by the
      addition of aesculin in a dose-dependent manner. However, gelatinolytic activity
      of MMP-9 was not reduced by aesculin. Luciferase activity assays and
      electrophoretic mobility shift assays using RAW264.7 cells showed that the
      inhibition of MMP-9 expression by aesculin was mediated by AP-1 rather than NF
      kappaB. In addition, aesculin inhibited phosphorylation of p38 MAPK and
      subsequent activation of c-fos, a component of AP-1 transcription factor, but not
      JNK, ERK1/2, and c-jun. These findings suggest that aesculin is a potent drug
      candidate that protects against the inflammatory destruction of ECM.

PMID- 22858580
TI  - Purification and antimicrobial function of ubiquitin isolated from the gill of
      Pacific oyster, Crassostrea gigas.
AB  - An antimicrobial polypeptide was purified from an acidified gill extract of
      Pacific oyster (Crassostrea gigas) by C(18) reversed-phase HPLC. The purified
      polypeptide had a molecular weight of 8471Da containing 74 amino acid residues.
      Comparison of the obtained N-terminal sequences with those of others revealed
      that it was identical to ubiquitin reported from other species and named
      cgUbiquitin. cgUbiquitin showed broad potent antimicrobial activity against Gram
      positive and -negative bacteria including Streptococcus iniae and Vibrio
      parahemolyticus (minimal effective concentrations, 7.8 and 9.8MUg/mL),
      respectively, without hemolytic activity. The cgUbiquitin cDNA was identified
      from an expressed sequence tag (EST) library of oyster gill as a precursor form,
      encoding ubiquitin consisting of 76 amino acids fused to ribosomal protein of
      S27. Although the cgUbiquitin precursor mRNA was expressed at the intermediate
      level in the gill, the mRNA was significantly up-regulated at 48h post injection
      with Vibrio sp. Analysis of the cgUbiquitin C-terminus by carboxypeptidase B
      treatment and comparison of the retention times revealed that cgUbiquitin lacks
      the terminal Gly-Gly doublet and ends in an C-terminal Arg residue which might be
      related to antimicrobial activity. Study of the kinetics of killing and membrane
      permeabilization showed that this peptide was not membrane permeable and acted
      through a bacteriostatic process. According to the homology modeling, this
      peptide is composed of three secondary structural motifs including three alpha
      helices and four beta-strands separated by 7 loops regions. Our results indicate
      that cgUbiquitin might be related to the innate immune defenses in the Pacific
      oyster and this is the first report for antimicrobial function of ubiquitin
      isolated from any oyster species.

PMID- 22858581
TI  - Synthesis of highly fluorescent water-soluble silver nanoparticles for selective
      detection of Pb(II) at the parts per quadrillion (PPQ) level.
AB  - This communication reports for the first time the synthesis of water-soluble
      glutathione protected highly fluorescence (Phi = 0.18) silver nanoparticles for
      the selective and highly sensitive sensing of Pb(ii) at the parts per quadrillion
      (PPQ) level.

PMID- 22858582
TI  - Multistage delivery of chemotherapeutic nanoparticles for breast cancer
      treatment.
AB  - Adequate drug delivery to tumors is hindered by barriers such as degradation and
      non-specific distribution. Nested incorporation of drug-containing nanoparticles
      within mesoporous silicon particles (MSVs), carriers rationally designed to
      enhance tumor transport, was hypothesized to result in pronounced and sustained
      antitumor efficacy. Paclitaxel (PTX)-containing poly(ethylene glycol)-block
      poly(epsilon-caprolactone) (PEG-PCL) polymer micelles were favorably loaded
      within MSVs, after which drug release was significantly delayed. Antitumor
      efficacy analyses in mice bearing MDA-MB-468 breast tumors demonstrated
      significant tumor growth suppression following a single administration. Results
      highlight effective chemotherapeutic shuttling and site-specific controlled
      release afforded by MSVs, potentially translating towards improvements in patient
      outcomes and morbidity.

PMID- 22858583
TI  - Monitoring of HAART regime antiretrovirals in serum of acquired immunodeficiency
      syndrome patients by micellar liquid chromatography.
AB  - A methodology based on micellar liquid chromatography to monitor five
      antiretroviral drugs (lamivudine, stavudine, tenofovir, zidovudine and efavirenz)
      was proposed. Antiretrovirals were studied in sets of three, corresponding to
      each highly active antiretroviral therapy (HAART) regime, prescribed to acquired
      immunodeficiency syndrome (AIDS)-infected patients. Four aqueous micellar mobile
      phases buffered at pH 7 were optimized to separate these compounds, using sodium
      dodecyl sulfate as the tensioactive, and 1-propanol or 1-pentanol as the organic
      modifier. The composition of each mobile phase was optimized for each
      antiretroviral. The common separation conditions were: C18 apolar column (125 *
      4.6 mm, 5 MUm particle size), UV detection set at 214 nm, and mobile phase
      running at 1 mL min(-1) without controlling the temperature. The finally
      suggested method was validated for five analysed antiretroviral drugs following
      the US Food and Drug Administration guidelines in terms of: linearity between 0.5
      and 50 ppm (r(2) > 0.9995), sensitivity (LOD lower than 0.25 ppm), intra- and
      inter-day precision (<7.1 and <5.2%, respectively) and accuracy (recovery 88.5
      105.3% and 93.5-101.3%, respectively), as well as robustness (<6.5%). The
      proposed method was used to monitor the level of antiretrovirals in the serum of
      AIDS patients. The suggested methodology was found to be useful in the routine
      analysis of antiretrovirals in serum samples.

PMID- 22858584
TI  - Solution behaviors and self-assembly of polyoxometalates as models of macroions
      and amphiphilic polyoxometalate-organic hybrids as novel surfactants.
AB  - Large, hydrophilic polyoxoanions with high solubility in water and/or other polar
      solvents demonstrate unique solution behavior by self-assembling into single
      layer, hollow, spherical "blackberry" structures, which is obviously different
      from small, simple ions. These macroions cannot be treated as insoluble colloidal
      suspensions because they form stable "real solutions". Counterion-mediated
      attraction is considered as the main driving force for the self-assembly
      behavior. The size disparity between the macroions and their counterions results
      in macroion-counterion pairing which leads to the inter-macroanionic attraction.
      The blackberries, with robust membranes semi-permeable to cations, can adjust
      their size accurately and reversibly in response to the change of solvent
      polarity and charge density of individual macroions. The inorganic macroions with
      well-defined size, shape, mass, charge density, but no intramolecular
      interactions, are ideal model systems to study the intermolecular interactions in
      polyelectrolyte and bio-macromolecular solutions. The blackberry structures show
      certain similarities to spherical viral capsids, from the overall structure to
      the formation kinetics. More amazingly, these inorganic macroions demonstrate
      some features usually believed to belong only to complex biological molecules,
      such as the self-recognition in dilute solutions. Meanwhile, polyoxometalates
      based organic-inorganic hybrid materials demonstrate amphiphilic properties by
      self-assembling into vesicles and reverse vesicles in polar and non-polar
      solvents, respectively, and form monolayer at the water/air interface. Different
      from conventional amphiphiles, these hybrids show pH-dependent and counterion
      dependent self-assembly behaviors with controllable functionality, e.g.
      fluorescence and catalytic activity, due to the high and tunable charges and the
      functionalities of POM polar head groups.

PMID- 22858585
TI  - Application of a highly sensitive detection system for epidermal growth factor
      receptor mutations in plasma DNA.
AB  - INTRODUCTION: : Detection of epidermal growth factor receptor (EGFR) mutations is
      indispensable to determine an appropriate lung cancer treatment. Although
      retreatment often prolongs survival, how to select the appropriate population for
      retreatment has not been clarified. METHODS: : We used novel methods to identify
      EGFR mutations: wild inhibiting polymerase chain reaction (PCR) and quenched
      probe system (WIP-QP) for exon 19 deletions and mutation-biased PCR and quenched
      probe system for L858R. After the detection limits were determined, we examined
      DNA isolated from lung cancer specimens and circulating plasma DNA samples of 39
      adenocarcinoma patients whose primary tumors harbored EGFR exon 19 deletions or
      L858R. RESULTS: : Detection limit was 0.005 to 0.04 ng in genomic DNA and 0.1% to
      0.3% in mutant plasmids. The results of cancer tissue specimens were identical to
      those with existing systems (nucleic acid-locked nucleic acid PCR clamp or
      cycleave PCR), except for two samples that showed both exon 19 deletions and
      L858R. One of the two samples was confirmed to harbor L858R mutation by allele
      specific oligonucleotide PCR; the other one did not. Exon 19 deletions and L858R
      were detected in 44.7% and 8.7% of patients, using plasma DNA, among those who
      carried the identical abnormalities in primary tumors all of cases that evidenced
      pathological stage IV except for one patient, suggesting that EGFR mutations
      might be preferentially detected in plasma DNA obtained from patients in advanced
      stages. Serial monitoring of these mutations with T790M, a gate keeper mutation,
      demonstrated correlation with disease state. CONCLUSIONS: : Our novel detection
      systems for EGFR mutations could be useful not only at the beginning of treatment
      but also for monitoring using plasma DNA for deciding appropriate treatment,
      including rechallenge with EGFR-tyrosine kinase inhibitors.

PMID- 22858586
TI  - Impact of anti-interleukin-6 receptor blockade on circulating T and B cell
      subsets in patients with systemic lupus erythematosus.
AB  - BACKGROUND: Circulating plasmablasts/plasma cells and activated B and T cells are
      increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces
      differentiation of B cells into antibody-forming cells and of T cells into
      effector cells. OBJECTIVE: To examine the hypothesis that blocking IL-6 would
      reverse some of the immune abnormalities present in SLE. METHODS: Fifteen
      patients with SLE with mild-to moderate disease activity were treated with
      biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal
      antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum
      immunoglobulin levels were compared at baseline and at weeks 6 and 12. RESULTS:
      Tocilizumab decreased activated T and B cells, the frequency of
      CD27(high)CD38(high)IgD- plasmablasts/plasma cells and IgD-CD27+ post-switched
      memory B cells as well as IgG+ memory B cell, whereas it increased the frequency
      of IgD+CD27- antigen-inexperienced B cells. Among antigen-inexperienced IgD+CD27-
      B cells, CD38(low) mature naive B cells increased significantly and
      CD38(Intermediate)CD5+ pre-naive B cells showed a decreasing trend, whereas
      CD38(high)CD5+ transitional type 1 B cells did not change. Most of the changes
      occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3
      serum levels decreased albeit within the normal range. The frequency of
      CD4+CD45RA+CCR7+ naive T cells increased. CONCLUSIONS: In vivo blockade of the IL
      6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis
      by either blocking differentiation and/or trafficking in patients with SLE and
      leads to normalisation of the abnormal B and T cell subsets seen at baseline.

PMID- 22858587
TI  - Increased serum IL-33 levels may indicate vascular involvement in systemic
      sclerosis.

PMID- 22858588
TI  - Chemical equilibria in the uranyl(VI)-peroxide-carbonate system; identification
      of precursors for the formation of poly-peroxometallates.
AB  - The focus of this study is on the identification of precursors in solution that
      might act as building blocks when solid uranyl(VI) poly-peroxometallate clusters
      containing peroxide and hydroxide bridges are formed. The precursors could be
      identified by using carbonate as an auxiliary ligand that prevented the formation
      of large clusters, such as the ones found in solids of fullerene type. Using data
      from potentiometric and NMR ((17)O and (13)C) experiments we identified the
      following complexes and determined their equilibrium constants:
      (UO(2))(2)(O(2))(CO(3))(4)(6-), UO(2)(O(2))CO(3)(2-), UO(2)(O(2))(CO(3))(2)(4-),
      (UO(2))(2)(O(2))(CO(3))(2)(2-), (UO(2))(2)(O(2))(2)(CO(3))(2-) and
      [UO(2)(O(2))(CO(3))](5)(10-). The NMR spectra of the pentamer show that all
      uranyl and carbonate sites are equivalent, which is only consistent with a ring
      structure built from uranyl units linked by peroxide bridges with the carbonate
      coordinated "outside" the ring; this proposed structure is very similar to
      [UO(2)(O(2))(oxalate)](5)(10-) identified by Burns et al. (J. Am. Chem. Soc.,
      2009, 131, 16648; Inorg. Chem., 2012, 51, 2403) in
      K(10)[UO(2)(O(2))(oxalate)](5).(H(2)O)(13); similar ring structures where oxalate
      or carbonate has been replaced by hydroxide are important structure elements in
      solid poly-peroxometallate complexes. The equivalent uranyl sites in
      (UO(2))(2)(O(2))(2)(CO(3))(2-) suggest that the uranyl-units are linked by the
      carbonate ion and not by peroxide.

PMID- 22858589
TI  - Cr(VI) induces the decrease of ATP level and the increase of apoptosis rate
      mediated by ROS or VDAC1 in L-02 hepatocytes.
AB  - The present study explored the ability of the voltage-dependent anion channel 1
      (VDAC1) mRNA and ROS levels to modulate the effects of hexavalent chromium Cr(VI)
      on the adenosine triphosphate (ATP) level and the rate of apoptotic cell death.
      Cultured L-02 cells were pretreated with 20mM N-acetyl-cysteine (NAC) for 24h or
      transiently transfected with small interfering RNAs targeting VDAC1 (siVDAC1) for
      48h; cells that were not pretreated were used as the control. The cells were
      subsequently treated with 0, 2, 8, or 32MUM Cr(VI) for 24h. Then, levels of VDAC1
      mRNA, ROS, and ATP and the apoptosis rate were measured by reverse-transcription
      quantitative PCR, fluorometry, a bioluminescence assay, and flow cytometry,
      respectively. The results showed that Cr(VI) at 32MUM led to increase in the ROS
      level, VDAC1 mRNA expression, and the apoptosis rate and a decrease in the ATP
      level; pretreatment with NAC led to the down-regulation in the levels of ROS,
      VDAC1 mRNA and apoptosis and the significant up-regulation in the ATP levels.
      Interestingly, after the pretreatment with siVDAC1 to inhibit VDAC1 mRNA
      expression, the increased apoptosis rates and decreased ATP levels were reversed
      as well. These results suggested that changes in the ROS or VDAC1 mRNA levels
      were associated with changes in the ATP level and apoptosis rate. Furthermore,
      correlation analysis confirmed the association between both the ROS and VDAC1
      levels and both the ATP level and the apoptosis rate. In conclusion, Cr(VI)
      induced ROS- and VDAC1-mediated decreases in ATP levels and increases in the
      apoptosis rate.

PMID- 22858590
TI  - Biochemical mapping of human NEIL1 DNA glycosylase and AP lyase activities.
AB  - Base excision repair of oxidized DNA in human cells is initiated by several DNA
      glycosylases with overlapping substrate specificity. The human endonuclease VIII
      homologue NEIL1 removes a broad spectrum of oxidized pyrimidine and purine
      lesions. In this study of NEIL1 we have identified several key residues, located
      in three loops lining the DNA binding cavity, important for lesion recognition
      and DNA glycosylase/AP lyase activity for oxidized bases in double-stranded and
      single-stranded DNA. Single-turnover kinetics of NEIL1 revealed that removal of 5
      hydroxycytosine (5-OHC) and 5-hydroxyuracil (5-OHU) is ~25 and ~10-fold faster in
      duplex DNA compared to single-stranded DNA, respectively, and also faster than
      removal of dihydrothymine (DHT) and dihydrouracil (DHU), both in double-stranded
      and single-stranded DNA. NEIL1 excised 8-oxoguanine (8-oxoG) only from double
      stranded DNA and analysis of site-specific mutants revealed that Met81, Arg119
      and Phe120 are essential for removal of 8-oxoG. Further, several arginine and
      histidine residues located in the loop connecting the two beta-strands forming
      the zincless finger motif and projecting into the DNA major groove, were shown to
      be imperative for lesion processing for both single- and double-stranded
      substrates. Trapping experiments of active site mutants revealed that the N
      terminal Pro2 and Lys54 can alternate to form a Schiff-base complex between the
      protein and DNA. Hence, both Pro2 and Lys54 are involved in the AP lyase
      activity. While wildtype NEIL1 activity almost exclusively generated a delta
      elimination product when processing single-stranded substrates, substitution of
      Lys54 changed this in favor of a beta-elimination product. These results suggest
      that Pro2 and Lys54 are both essential for the concerted action of the beta,delta
      elimination in NEIL1.

PMID- 22858591
TI  - Nitric oxide coupling mediated by iron porphyrins: the N-N bond formation step is
      facilitated by electrons and a proton.
AB  - The coupling of two NO molecules catalyzed by iron porphyrins is of biological
      importance. We use density functional theory calculations to examine the factors
      that control the fundamental N-N bond formation step mediated by a single iron
      porphyrin. The presence of an axial Im ligand, extra electrons, and most
      importantly a proton, enhance the N-N bond formation step in our model.

PMID- 22858592
TI  - Fetal neurology: volume II.

PMID- 22858593
TI  - Fetal neurology: volume I.

PMID- 22858594
TI  - Eliminating the dication-induced intersample chemical-shift variations for NMR
      based biofluid metabonomic analysis.
AB  - NMR-based urinary metabonomic analysis is an essential aspect of systems biology
      for understanding mammalian physiology and pathophysiology though intersample
      chemical-shift variations can cause serious problems. Here, we report two
      optimized and validated methods to eliminate such variations resulting from
      intersample differences in pH and dication concentration. We found that the
      Ca(2+) concentration was 7.41 +/- 3.48, 1.03 +/- 0.34 and 0.87 +/- 0.52 mM
      whereas the Mg(2+) concentration was 3.02 +/- 1.41, 2.65 +/- 1.20 and 0.80 +/-
      0.59 mM in rat, mouse and human urine samples, respectively; urinary Ca-EDTA, Mg
      EDTA and free EDTA had spin-lattice relaxation time values (600.13 MHz) of 0.38,
      0.41 and 0.55 s, respectively. We also found that the combined treatments with
      potassium fluoride, phosphate buffer and a small amount of K(3)EDTA eliminated
      intersample chemical-shift variations for all metabolites. EDTA treatment
      followed with phosphate buffer also achieved similar results although resonances
      from EDTA and its complexes obscured some metabolite signals. We systematically
      optimized the amount of additives for rat, mouse and human urine samples taking
      into consideration the pH control, signal-to-noise ratio and intersample
      uniformity for metabolite chemical-shifts. Based on thorough validation, we
      established some optimized procedures for rat, mouse and human urine,
      respectively. By eliminating both pH and dication effects, these methods enable
      the reduction of intersample chemical-shift variations to 1.5 Hz for all
      metabolites. The methods will offer ensured data quality for high-throughput,
      especially robotic urinary metabonomics studies with no need for peak alignments
      or corrections.

PMID- 22858595
TI  - Tumor suppressor menin mediates peripheral nerve injury-induced neuropathic pain
      through potentiating synaptic plasticity.
AB  - Synaptic plasticity is a crucial step in the development of central sensitization
      in the pathogenesis of neuropathic hyperalgesia. Menin, the product of the
      multiple endocrine neoplasia type 1 (MEN1) gene, possesses the property of
      synaptogenesis which plays an essential role in neuronal activity. We tested the
      contributing role of spinal menin in peripheral nerve injury-induced neuropathic
      hypersensitivity through modulating neuronal synaptic plasticity. After approval
      by the Institutional Animal Care and Use Committee, nociceptive responses were
      detected with von Frey filaments and thermal plate after spared nerve injury in
      C57BL/6 mice who were treated with either intrathecal antisense oligonucleotide
      of MEN1 (ASO) or vehicle. Extracellular spontaneous discharge frequency, field
      excitatory postsynaptic potential (fEPSP), and monosynaptic excitatory
      postsynaptic currents (EPSCs) were measured electrophysiologically. Intrathecal
      ASO alleviated nerve injury-induced mechanical and thermal hypersensitivity.
      Upregulated spinal menin after nerve injury colocalized with NeuN in the
      superficial laminae; genetic knockdown of spinal menin reduced nerve injury
      induced in vivo spontaneous activity and instantaneous frequency and in vitro
      field potentials; ASO decreased the frequency and amplitude of monosynaptic
      EPSCs, and reduced synaptic strength and total charge. Collectively, these
      findings highlight the role of upregulated neuronal menin in the spinal cord in
      potentiating spinal synaptic plasticity in peripheral nerve injury-induced
      neuropathic hypersensitivity.

PMID- 22858596
TI  - Dendritic morphology changes in neurons from the prefrontal cortex, hippocampus
      and nucleus accumbens in rats after lesion of the thalamic reticular nucleus.
AB  - Several studies in rodents have shown that dysfunctions of the thalamic reticular
      nucleus (TRN) result in deficits of sensory gating and attentional processes, two
      core features of schizophrenia. TRN receives inputs from the prefrontal cortex
      (PFC) and hippocampal formation, two structures which send excitatory projections
      to the nucleus accumbens (NAcc) and are interconnected with the basolateral
      amygdala (BLA). Here we determined whether (and which) changes occurred four
      weeks after a TRN lesion in the dendritic morphology of pyramidal neurons of
      layers 3 and 5 of the PFC, neurons of ventral and dorsal hippocampus, BLA, and
      the medium spiny neurons of the NAcc. Dendritic morphology and characteristics
      were measured by using Golgi-Cox procedure followed by Sholl analysis. We also
      evaluated the effects of TRN lesion on exploratory behavior assessed by hole
      board test and locomotor activity induced by a novel environment. We found that
      TRN damage induced a reduction in the exploratory behavior measured by hole-board
      test with neuronal hypotrophy in PFC (layer 5), CA1 ventral hippocampus and NAcc
      neurons. Taken together, these data suggest that the behavioral and morphological
      effects of TRN lesion are, at least partially, mediated by limbic subregions with
      possible consequences for schizophrenia-related behaviors.

PMID- 22858597
TI  - Glutamate injection into the cuneiform nucleus in rat, produces correlated single
      unit activities in the Kolliker-Fuse nucleus and cardiovascular responses.
AB  - The cuneiform (CnF) and Kolliker-Fuse (KF) nuclei are implicated in several
      functions including regulation of cardiovascular system and pain modulation. The
      KF also is a potential candidate for relaying the CnF cardiovascular responses to
      the rostral ventrolateral medulla (RVLM). In a previous study we showed that
      blockade of the KF strongly attenuated the short responses and moderately
      attenuated the long responses to glutamate microinjection into the CnF,
      suggesting that the cardiovascular effects of the CnF, especially the short
      responses, were mediated by the KF. In the present study the cellular basis of
      the cardiovascular responses of the CnF and possible role of the KF in relaying
      them to the RVLM were explored. In one group, l-glutamate was microinjected in
      the CnF and the cardiovascular responses were recorded. In another group the
      single unit responses of the KF to l-glutamate injection into the CnF were
      recorded. Our results showed that chemical stimulation of the CnF with glutamate
      produced mainly excitatory cardiovascular and single unit responses and a
      minority of mixed (excitatory and inhibitory) responses. In about one fourth of
      the cases there were no responses to stimulation. Various patterns of each group
      were presented and compared between cardiovascular and single unit responses.
      Similarities were found between cardiovascular and single unit response patterns,
      suggesting a significant role of KF neurons in mediating the CnF cardiovascular
      responses to the RVLM.

PMID- 22858599
TI  - The endovascular management of a neurofibromatosis vasculopathy: a case report.
AB  - We describe the management of a 30-year-old male with type I neurofibromatosis
      who required an above-knee amputation for bleeding, infection, swelling, and
      multiple severe joint instability. Postoperatively, he continued to bleed from
      the stump site. Angiography revealed multiple small distal bleeding aneurysms.
      Hemostasis was eventually achieved with standard microcoil embolization.

PMID- 22858598
TI  - Dorsal root ganglion neurons innervating pelvic organs in the mouse express
      tyrosine hydroxylase.
AB  - Previous studies in rat and mouse documented that a subpopulation of dorsal root
      ganglion (DRG) neurons innervating non-visceral tissues express tyrosine
      hydroxylase (TH). Here we studied whether or not mouse DRG neurons retrogradely
      traced with Fast Blue (FB) from colorectum or urinary bladder also express
      immunohistochemically detectable TH. The lumbar sympathetic chain (LSC) and major
      pelvic ganglion (MPG) were included in the analysis. Previously characterized
      antibodies against TH, norepinephrine transporter type 1 (NET-1) and calcitonin
      gene-related peptide (CGRP) were used. On average, ~14% of colorectal and ~17% of
      urinary bladder DRG neurons expressed TH and spanned virtually all neuronal
      sizes, although more often in the medium-sized to small ranges. Also, they were
      more abundant in lumbosacral than thoracolumbar DRGs, and often coexpressed CGRP.
      We also detected several TH-immunoreactive (IR) colorectal and urinary bladder
      neurons in the LSC and the MPG, more frequently in the former. No NET-1-IR
      neurons were detected in DRGs, whereas the majority of FB-labeled, TH-IR neurons
      in the LSC and MPG coexpressed this marker (as did most other TH-IR neurons not
      labeled from the target organs). TH-IR nerve fibers were detected in all layers
      of the colorectum and the urinary bladder, with some also reaching the basal
      mucosal cells. Most TH-IR fibers in these organs lacked CGRP. Taken together, we
      show: (1) that a previously undescribed population of colorectal and urinary
      bladder DRG neurons expresses TH, often CGRP but not NET-1, suggesting the
      absence of a noradrenergic phenotype; and (2) that TH-IR axons/terminals in the
      colon or urinary bladder, naturally expected to derive from autonomic sources,
      could also originate from sensory neurons.

PMID- 22858600
TI  - Surgical femorocaval bypass for recalcitrant iliofemoral venous occlusion to
      endovascular treatment.
AB  - Patients with chronic occlusion of iliac veins may present with symptoms ranging
      from mild discomfort to severe disability, including limb swelling, venous
      claudication, and ulceration. Endovascular treatment has emerged as first line of
      interventional therapy. Surgical venous-venous bypasses for the management of
      these patients in the era of endovascular therapy are rarely performed. These
      procedures are reserved only for patients with severe symptoms and long occlusive
      lesions that have failed previous endovascular interventions. We present a
      clinical scenario involving the use of femorocaval bypass to treat an iliofemoral
      occlusion recalcitrant to stenting, manifesting with severe lower extremity
      swelling and venous claudication. The surgical bypass resulted in significant
      improvement in the patient's clinical status.

PMID- 22858601
TI  - Engineering polyoxometalates with emergent properties.
AB  - Polyoxometalates are clusters of metal-oxide units, comprising a large diversity
      of nanoscale structures, and have many common building blocks; in fact
      polyoxometalate clusters are perhaps the largest non-biologically derived
      molecules structurally characterised. Not only can polyoxometalates have gigantic
      nanoscale molecular structures, but they also a have a vast array of physical
      properties, many of which can be specifically 'engineered-in'. Here we describe
      how building block libraries of polyoxometalates can be used to construct systems
      with important catalytic, electronic, and structural properties. We also show
      that it is possible to construct complex chemical systems based upon
      polyoxometalates, manipulating the templating/self templating rules to exhibit
      emergent processes from the molecular to the macroscopic scale.

PMID- 22858602
TI  - Accumulation of selenium in Ulva sp. and effects on morphology, ultrastructure
      and antioxidant enzymes and metabolites.
AB  - The impact of selenium (Se) on Ulva sp., a green macroalga naturally growing in
      the Venice Lagoon, was investigated. The alga was provided for 10 days with
      concentrations of selenate (Na(2)SeO(4)) ranging from 0 to 100 MUM. Se
      accumulation in the algal biomass was linearly related to the selenate dose and
      this relationship was not affected by the high sulfate concentration measured in
      the seawater. The amount of Se measured in the alga was always relatively low and
      not hazardous to algal consumers. However, Se induced the formation of hydrogen
      peroxide (H(2)O(2)) in Ulva sp. and, as a result, the activity of antioxidant
      enzymes (superoxide dismutase, SOD, and catalase, CAT) and the amount of
      antioxidant metabolites (phenols, flavonoids and carotenoids) increased, even
      when selenate was supplied to the macroalga at low concentration (2.5 MUM). This
      indicated that different components of the antioxidant defence system played a
      pivotal role in overcoming oxidative damage by Se in the macroalga, and explained
      the lack of morphological and ultrastructural alterations in Ulva sp. exposed to
      selenate.

PMID- 22858603
TI  - A transgenic embryonic sexing system for Anastrepha suspensa (Diptera:
      Tephritidae).
AB  - The Sterile Insect Technique (SIT) is a highly successful biologically-based
      strategy to control pest insect populations that relies on the large-scale
      release of sterilized males to render females in the field non-reproductive. For
      medfly, a mutant-based sexing system is available as well as a transgenic system
      where a tetracycline-suppressible (Tet-off) toxic molecule is female-specifically
      produced. However, the former classical genetic system took many years to refine,
      and the latter system results in female death by a poorly understood mechanism,
      primarily in the pupal stage after rearing costs have been incurred. Here we
      describe a Tet-off transgenic embryonic sexing system (TESS) for Anastrepha
      suspensa that uses a driver construct having the promoter from the embryo
      specific A. suspensa serendipity alpha gene, linked to the Tet-transactivator.
      This was used to drive the expression of a phospho-mutated variant of the pro
      apoptotic cell death gene, Alhid, from Anastrepha ludens. The system uses a sex
      specific intron splicing cassette linked to a cell death gene lethal effector.
      Progeny from TESS strains heterozygous for the transgene combination were 80-100%
      males, whereas four double homozygous TESS strains had 100% male-only progeny,
      with female death limited primarily to embryogenesis. In a large-scale test, more
      than 30,000 eggs from two strains resulted in 100% male-only progeny. The
      transgenic sexing approach described here is highly effective and cost-efficient
      by eliminating most, if not all, female insects early in embryogenesis using a
      well-characterized apoptotic mechanism.

PMID- 22858604
TI  - Traffic emission factors of ultrafine particles: effects from ambient air.
AB  - Ultrafine particles have a significant detrimental effect on both human health
      and climate. In order to abate this problem, it is necessary to identify the
      sources of ultrafine particles. A parameterisation method is presented for
      estimating the levels of traffic-emitted ultrafine particles in terms of
      variables describing the ambient conditions. The method is versatile and could
      easily be applied to similar datasets in other environments. The data used were
      collected during a four-week period in February 2005, in Gothenburg, as part of
      the Gote-2005 campaign. The specific variables tested were temperature (T),
      relative humidity (RH), carbon monoxide concentration (CO), and the concentration
      of particles up to 10 MUm diameter (PM(10)); all indicators are of importance for
      aerosol processes such as coagulation and gas-particle partitioning. These
      variables were selected because of their direct effect on aerosol processes (T
      and RH) or as proxies for aerosol surface area (CO and PM(10)) and because of
      their availability in local monitoring programmes, increasing the usability of
      the parameterization. Emission factors are presented for 10-100 nm particles
      (ultrafine particles; EF(ufp)), for 10-40 nm particles (EF(10-40)), and for 40
      100 nm particles (EF(40-100)). For EF(40-100) no effect of ambient conditions was
      found. The emission factor equations are calculated based on an emission factor
      for NO(x) of 1 g km(-1), thus the particle emission factors are easily expressed
      in units of particles per gram of NO(x) emitted. For 10-100 nm particles the
      emission factor is EF(ufp) = 1.8 * 10(15) * (1 - 0.095 * CO - 3.2 * 10(-3) * T)
      particles km(-1). Alternative equations for the EFs in terms of T and PM(10)
      concentration are also presented.

PMID- 22858605
TI  - The structures of type I polyketide synthases.
AB  - With the recent structural characterization of each of the component enzymes of
      type I polyketide synthases, scientists are coming tantalizingly close to
      elucidating the overall architectures and mechanisms of these enormous molecular
      factories. This review highlights not only what has been revealed about the
      structures and activities of each of the domains but also the mysteries that
      remain to be solved.

PMID- 22858606
TI  - The effect of furcated hydrogen bond and coordination bond on luminescent
      behavior of metal-organic framework [CuCN.EIN]: a TDDFT study.
AB  - The hydrogen bonding in electronically excited-state of the metal-organic
      framework [CuCN.EIN] was studied using time-dependent density functional theory
      (TDDFT). The representative fragment of [CuCN.EIN] was employed for the
      computation. The geometric structures, binding energies and IR spectra in both
      ground state and electronically excited state S(1) of the complex were computed
      using DFT and TDDFT methods to investigate excited-state hydrogen-bonding and
      coordination bonding, respectively. Based on the analysis of the frontier
      molecular orbitals and the electronic configuration of the complex, the ligand-to
      metal charge transfer (LMCT) luminescence was confirmed. Furthermore, furcated
      hydrogen bonds are both strengthened in the S(1) state slightly. And then, the
      strengthening of the hydrogen bonds in the S(1) state goes against the charge
      transfer from ligand to metal and then should be in favor of the luminescence. In
      particular, we also discuss strengthening or weakening behavior of the
      coordination bonds in the S(1) state for the first time. Based on the results of
      the bond lengths and vibration frequency of the coordination bond, we can
      conclude that the coordination bond Cu(7)-N(8) is strengthened in the S(1) state.
      And the strengthening of the coordination bond Cu(7)-N(8) should also be in favor
      of the luminescence.

PMID- 22858607
TI  - Structures, properties and nature of DMSO-XY (XY=ClF and BrF) complexes: redshift
      and blueshift of S=O stretch.
AB  - The DMSO-XY (XY=ClF and BrF) complexes have been investigated with quantum
      chemical calculations. In general, two minima complexes were found, one with an
      O...X halogen bond and the other one with a S...X halogen bond. The former is
      more stable than the latter. Additionally, one first order saddle point complex
      was also observed. The interaction energies in the S complexes suffer a prominent
      influence from the calculation methods. At the CCSD(T)/aug-cc-pVDZ level, the
      interaction energies are calculated to be -9.19 and -12.73 kcal/mol for the Cl
      and Br global minima, respectively. Both complexes have also been evidenced to be
      stable at room temperature. The SO stretch vibration exhibits a red shift at the
      global minimum but a blue shift at the local minimum, whereas the CSC and CH
      stretch vibrations move to high frequency in both cases. The energy decomposition
      analyses indicate that the electrostatic interaction plays a dominant role in
      stabilizing these halogen-bonded complexes.

PMID- 22858608
TI  - 6-Phenyl-3-(4-pyridyl)-1,2,4-triazolo-[3,4-b][1,3,4]thiadiazole: synthesis,
      experimental, theoretical characterization and biological activities.
AB  - The molecular geometry, vibrational frequencies, and gauge including atomic
      orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in
      the ground state have been calculated using the Hartree-Fock (HF) and density
      functional theory (DFT) methods with 6-31G(d) basis sets, and compared with the
      experimental data. The calculated results show that the optimized geometries can
      well reproduce the crystal structural parameters and the theoretical vibrational
      frequencies, and (1)H and (13)C NMR chemical shift values show good agreement
      with experimental data. To determine conformational flexibility, molecular energy
      profile of the title compound was obtained by HF/6-31G(d) and (DFT/B3LYP)
      calculations with respect to selected degree of torsional freedom, which was
      varied from -180 degrees  to +180 degrees  in steps of 10 degrees . The energetic
      behavior of the title compound in solvent media was examined using the B3LYP
      method with the 6-31G(d) basis set by applying the Onsager and the polarizable
      continuum model (PCM). The results obtained with these methods reveal that the
      PCM method provided more stable structure than Onsager's method. The title
      compound has been tested in vitro for biological effects.

PMID- 22858609
TI  - Short-range interactions between surfactants, silica species and EDTA4- salt
      during self-assembly of siliceous mesoporous molecular sieve: a UV Raman study.
AB  - The effects of surfactants, counterions and additive salts on the formation of
      siliceous mesoporous molecular sieves during self-assembly process were
      investigated by UV Raman spectroscopy, X-ray diffraction (XRD) and transmission
      electron microscopy (TEM) techniques. The surfactant molecules experience the
      rearrangement after adding the silica species and adjusting the pH value. The
      obvious change of the Raman bands related to the surfactants supports a
      cooperative interaction between surfactant and inorganic species during self
      assembly process. The addition of EDTANa(4) to the system induces the interaction
      between the COO(-) groups of EDTA(4-) and silanol groups of silica and a strong
      interaction between the EDTA(4-) and the N(+)(CH(3))(3) groups of the surfactant.
      The above interactions may be the main reason for the salt effect. The new
      information from the change of the chemical bonds allows for a further analysis
      to the interactions of different salts between surfactants and silica species at
      molecular level.

PMID- 22858610
TI  - X-ray diffraction, vibrational and quantum chemical investigations of 2-methyl-4
      nitroanilinium trichloroacetate trichloroacetic acid.
AB  - The structural investigations of the molecular complex of 2-methyl-4-nitroaniline
      with trichloroacetic acid, namely 2-methyl-4-nitroanilinium trichloroacetate
      trichloroacetic acid (C(11)H(10)Cl(6)N(2)O(6)) have been performed by means of
      single crystal and powder X-ray diffraction method. The complex was formed with
      accompanying proton transfer from trichloroacetic acid molecule to 2-methyl-4
      nitroaniline. The studied crystal is built up of singly protonated 2-methyl-4
      nitroanilinium cations, trichloroacetate anions and neutral trichloroacetic acid
      molecules. The crystals are monoclinic, space group P2(1)/c, with a=14.947A,
      b=6.432A, c=19.609A and Z=4. The vibrational assignments and analysis of 2-methyl
      4-nitroanilinium trichloroacetate trichloroacetic acid have also been performed
      by FTIR, FT-Raman and far-infrared spectral studies. More support on the
      experimental findings were added from the quantum chemical studies performed with
      DFT (B3LYP) method using 6-31G, cc-pVDZ, 6-31G and 6-31++G basis sets. The
      structural parameters, energies, thermodynamic parameters and the NBO charges of
      2M4NATCA were also determined by the DFT methods.

PMID- 22858611
TI  - Coupling technique of self-ordered ring and phosphorimetry for the determination
      of alkaline phosphatase and diseases prediction.
AB  - Rhodamine S could emit strong and stable room temperature phosphorescence (RTP)
      on polyamide membrane (PAM) in the presence of heavy atom perturber Pb(2+). When
      Rhodamine S-piperidine solution was dropped on PAM, the red (Rhod.S)(n)-P-SOR
      (Rhod.S, (Rhod.S)(n), P and SOR refer to alizarin red S, multiple Rhod.S
      molecules, piperidine and self-ordered ring, respectively) formed on PAM, leading
      to the enhancement of room temperature phosphorimetry (RTP) intensity (I(p),
      117.2) of (Rhod.S)(n)-P-SOR system, which was 2.4 times higher than that without
      SOR (I(p), 48.1). Wheat germ agglutinin (WGA) was labelled with (Rhod.S)(n)-P-SOR
      by the -NH- of Rhod.S reacting with the -COOH of WGA to form WGA-(Rhod.S)(n)-P
      SOR. The formation of WGA-AP-WGA-(Rhod.S)(n)-P-SOR in the affinity adsorption
      (AA) reaction carried out between the -COOH of WGA in WGA-(Rhod.S)(n)-P-SOR and
      the -NH(2) of alkaline phosphatase (AP) caused the RTP intensity (DeltaI(p)) of
      the WGA-AP-WGA-(Rhod.S)(n)-P-SOR system 7.8 times larger than that without
      (Rhod.S)(n)-P-SOR. Therefore, the coupling technique of SOR and solid substrate
      room temperature phosphorimetry (SS-RTP) for the determination of trace AP has
      been established. This method possessed good selectivity, high sensitivity
      (Detection limit (L.D) was 3.4*10(-16)gmL(-1)) and accuracy, and it has been
      applied to the determination of trace AP in human serum and the forecast of human
      diseases, and the results agreed well with those obtained by enzyme-linked
      immunoassay (ELISA). Besides, the mechanism of the coupling technique for the
      determination of AP was discussed.

PMID- 22858612
TI  - Research on the optical spectra, g factors and defect structures for two
      tetragonal Y2+ centers in the irradiated CaF2: Y crystal.
AB  - Based on the defect models that the tetragonal Y(2+) (1) center in the irradiated
      CaF(2): Y crystal is due to Y(2+) at Ca(2+) site associated with a nearest
      interstitial F(-) ion along C(4) axis and the tetragonal Y(2+) (2) center is
      Y(2+) at Ca(2+) site where the tetragonal distortion is caused by the static Jahn
      Teller effect, the two optical spectral bands and anisotropic g factors for both
      tetragonal Y(2+) centers are calculated. The calculations are made by using two
      methods based on the cluster approach, one is the complete diagonalization (of
      energy matrix) method (CDM) and another is the perturbation theory method (PTM).
      The calculated results for each Y(2+) center from CDM and PTM coincide and show
      reasonable agreement with the experimental values. The calculated isotropic g
      factor for Y(2+) (2) center at higher temperature owing to the dynamical Jahn
      Teller effect is also consistent with the observed value. The defect structures
      (i.e., tetragonal distortion) of the two Y(2+) centers are obtained from the
      calculation. It appears that both theoretical methods can be applied to explain
      the optical and EPR data, to study the defect model and to determine the defect
      structures for d(1) ions in crystals.

PMID- 22858613
TI  - Thermally stable water insoluble azo-azomethine dyes: synthesis, characterization
      and solvatochromic properties.
AB  - Six new water insoluble azo-azomethine dyes have been synthesized via
      condensation reaction of alpha,alpha'-bis(o-aminophenylthio)-1,2-xylene with
      substituted azo-coupled salicylaldehyde. The condensation reaction provides the
      expected bis-iminated azo-azomethine dyes in good yields, ranging from 59% to
      90%. The dyes have been characterized by IR, UV-Vis and (1)H NMR spectroscopic
      methods as well as elemental analysis. The thermal behavior of the prepared dyes
      has been determined using thermogravimetry technique. Furthermore, the effect of
      various organic solvents with different polarities on the UV-Vis spectra of the
      dyes has been also studied.

PMID- 22858614
TI  - An evidence-based systematic review of directional microphones and digital noise
      reduction hearing aids in school-age children with hearing loss.
AB  - PURPOSE: The purpose of this evidence-based systematic review was to evaluate the
      efficacy of digital noise reduction and directional microphones for outcome
      measures of audibility, speech recognition, speech and language, and self- or
      parent-report in pediatric hearing aid users. METHOD: The authors searched 26
      databases for experimental studies published after 1980 addressing one or more
      clinical questions and meeting all inclusion criteria. The authors evaluated
      studies for methodological quality and reported or calculated   p values and
      effect sizes when possible. RESULTS: A systematic search of the literature
      resulted in the inclusion of 4 digital noise reduction and 7 directional
      microphone studies (in 9 journal articles) that addressed speech recognition,
      speech and language, and/or self- or parent-report outcomes. No digital noise
      reduction or directional microphone studies addressed audibility outcomes.
      CONCLUSIONS: On the basis of a moderate level of evidence, digital noise
      reduction was not found to improve or degrade speech understanding. Additional
      research is needed before conclusions can be drawn regarding the impact of
      digital noise reduction on important speech, language, hearing, and satisfaction
      outcomes. Moderate evidence also indicates that directional microphones resulted
      in improved speech recognition in controlled optimal settings; however,
      additional research is needed to determine the effectiveness of directional
      microphones in actual everyday listening environments.

PMID- 22858615
TI  - An evidence-based systematic review of frequency lowering in hearing aids for
      school-age children with hearing loss.
AB  - PURPOSE: We developed 1 clinical question for this review, which addressed the
      comparison of hearing aids using frequency lowering compared to conventional
      processing amplification for outcomes of audibility, speech recognition, speech
      and language, and self- or parent-report for children with hearing loss. METHOD:
      We systematically searched 26 databases for studies addressing a clinical
      question and meeting all inclusion criteria. We evaluated studies for
      methodological quality and reported or calculated effect sizes when possible.
      RESULTS: The literature search resulted in the inclusion of 5 studies. We
      implemented several different frequency-lowering strategies across studies; 2
      studies used nonlinear frequency compression, 2 used frequency transposition, and
      1 used frequency compression with dynamic consonant boost. CONCLUSIONS: Whereas
      methodological limitations of the included studies preclude the formulation of
      strong conclusions, findings were generally positive across frequency-lowering
      strategies and outcomes. Additional high-quality research is needed in this area.

PMID- 22858616
TI  - An evidence-based systematic review of amplitude compression in hearing aids for
      school-age children with hearing loss.
AB  - PURPOSE: Two clinical questions were developed: one addressing the comparison of
      linear amplification with compression limiting to linear amplification with peak
      clipping, and the second comparing wide dynamic range compression with linear
      amplification for outcomes of audibility, speech recognition, speech and
      language, and self- or parent report in children with hearing loss. METHOD:
      Twenty-six databases were systematically searched for studies addressing a
      clinical question and meeting all inclusion criteria. Studies were evaluated for
      methodological quality, and effect sizes were reported or calculated when
      possible. RESULTS: The literature search resulted in the inclusion of 8 studies.
      All 8 studies included comparisons of wide dynamic range compression to linear
      amplification, and 2 of the 8 studies provided comparisons of compression
      limiting versus peak clipping. CONCLUSIONS: Moderate evidence from the included
      studies demonstrated that audibility was improved and speech recognition was
      either maintained or improved with wide dynamic range compression as compared
      with linear amplification. No significant differences were observed between
      compression limiting and peak clipping on outcomes (i.e., speech recognition and
      self-/parent report) reported across the 2 studies. Preference ratings appear to
      be influenced by participant characteristics and environmental factors. Further
      research is needed before conclusions can confidently be drawn.

PMID- 22858617
TI  - Accuracy of chest radiography plus electrocardiogram in diagnosis of hypertrophy
      in hypertension.
AB  - BACKGROUND: Chest radiography and electrocardiogram have been criticized due to
      their low sensitivity for Left Ventricular Hypertrophy diagnosis compared to
      echocardiogram. This one, however, is not available in primary health care
      centers to all hypertensive population. OBJECTIVE: To evaluate whether the
      association chest radiography-electrocardiogram provides the accuracy to justify
      its use in left ventricular hypertrophy detection in hypertensive patients, as
      well as the usefulness of the cardiothoracic ratio and oblique radiographs in
      relation to frontal and lateral views in evaluating dimensions of left cardiac
      chambers. METHODS: This was a prospective study including 177 consecutive
      hypertensive patients through chest radiography, electrocardiogram and
      echocardiography. Accuracy test was used to compare these methods using
      echocardiography as gold standard. RESULTS: The cardiothoracic ratio showed 17%
      sensitivity for detection of left ventricular hypertrophy, only indicating
      cardiac alterations at an advanced stage. Frontal plus lateral views showed
      sensitivity of 52%, which rose to 54% when chest radiography was associated with
      electrocardiogram. The oblique views did not significantly improve chest
      radiography accuracy. Chest radiography presented high specificity and elevated
      sensitivity for detection of aortal enlargement. Interestingly, this alteration
      was present in half of the hypertensive patients with left ventricular
      hypertrophy. CONCLUSION: We conclude that the association chest radiography
      electrocardiogram is useful for the screening of hypertensive patients for the
      diagnosis of left ventricular hypertrophy, especially if echocardiogram is
      unavailable.

PMID- 22858618
TI  - eNOS correlates with mitochondrial biogenesis in hearts of congenital heart
      disease with cyanosis.
AB  - BACKGROUND: Mitochondrial biogenesis program in heart appears to exhibit adaptive
      remodeling following biomechanical and oxidative stress. The adaptive mechanisms
      that protect myocardium metabolism during hypoxia are coordinated in part by
      nitric oxide (NO). OBJECTIVE: To observe mitochondrial biogenesis and nitric
      oxide synthase (NOS) expression in hearts of congenital heart disease with
      cyanosis, discuss mitochondrial response to chronic hypoxia in myocardium.
      METHODS: 20 patients with cyanotic (n=10) or acyanotic cardiac defects (n=10)
      were investigated. Samples from the right ventricular outflow tract myocardium
      taken during operation were studied. Morphometric analysis of mitochondria was
      performed with transmission electron microscope. Relative mtDNA/nDNA ratio was
      determined with real-time PCR. Cytochrome c oxidase subunit I (COXI), peroxisome
      proliferator-activated receptor I3 coactivator-1alpha (PGC-1alpha), nuclear
      respiratory factor 1 (NRF1), and mitochondrial transcription factor A (Tfam)
      transcript levels were detected by real-time fluorescent RT-PCR. COXI and nNOS,
      iNOS and eNOS protein levels were measured with western blot. RESULTS:
      Mitochondrial volume density (Vv) and numerical density (Nv) were significantly
      elevated in patients with cyanotic compared to acyanotic congenital heart
      disease. Elevated mtDNA and up-regulated COXI, PGC-1alpha, NRF1 and Tfam mRNA
      levels were observed in cyanotic patients. Protein levels of COXI and eNOS were
      significantly higher in the myocardium of cyanotic than of acyanotic patients.
      PGC-1alpha transcript levels correlated with the levels of eNOS. CONCLUSION:
      Mitochondrial biogenesis is activated in right ventricular outflow tract
      myocardium in congenital heart disease with cyanosis, which could be the adaptive
      response to chronic hypoxia and possibly involves eNOS up-regulation.

PMID- 22858619
TI  - Hydrogen peroxide and glucose biosensor based on silver nanowires synthesized by
      polyol process.
AB  - Silver nanowires synthesized through a polyol process using polyvinylpyrrolidone
      as protection (PVP-AgNWs) were used as a new electrode material for constructing
      a sensor. Hydrogen peroxide (H(2)O(2)) and glucose were used as analytes to
      demonstrate the sensor performance of the PVP-AgNWs. It is found that the PVP
      AgNWs-modified glassy carbon electrode (PVP-AgNWs/GCE) exhibits remarkable
      catalytic performance toward H(2)O(2) reduction. This sensor has a fast
      amperometric response time of less than 2 s and the catalytic current is linear
      over the concentration of H(2)O(2) ranging from 20 MUM to 3.62 mM (R = 0.998)
      with a detection limit of 2.3 MUM estimated on a signal-to-noise ratio of 3. A
      glucose biosensor was constructed by immobilizing glucose oxidase (GOD) onto the
      surface of the PVP-AgNWs/GCE. The resultant glucose biosensor can be used for
      glucose detection in human blood serum with a sensitivity of 15.86 MUA mM(-1) cm(
      2) and good selectivity and stability.

PMID- 22858620
TI  - Muscarinic acetylcholine receptors enhance neonatal mouse hypoglossal motoneuron
      excitability in vitro.
AB  - In brain stem slices from neonatal (postnatal days 0-4) CD-1 mice, muscarinic ACh
      receptors (MAChRs) increased rhythmic inspiratory-related and tonic hypoglossal
      nerve discharge and depolarized single hypoglossal motoneurons (HMs) via an
      inward current without changing input resistance. These responses were blocked by
      the MAChR antagonist 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP;
      100 nM). MAChRs shifted voltage-dependent activation of the hyperpolarization
      activated cation current to more positive levels. MAChRs increased the HM
      repetitive firing rate and decreased rheobase, with both effects being blocked by
      4-DAMP. Muscarinic agonists reduced the afterhyperpolarization of single action
      potentials (APs), suggesting that small-conductance Ca(2+)-dependent K(+) current
      inhibition increased the HM firing rate. Muscarinic agonists also reduced the AP
      amplitude and slowed its time course, suggesting that MAChRs inhibited voltage
      gated Na(+) channels. To compare muscarinic excitation of single HMs to
      muscarinic excitatory effects on motor output in thicker brain stem slices
      requiring higher extracellular K(+) for rhythmic activity, we tested the effects
      of muscarinic agonists on single HM excitability in high-K(+) artificial
      cerebrospinal fluid (aCSF). In high-K(+) aCSF, muscarinic agonists still
      depolarized HMs and altered AP size and shape, as in standard aCSF, but did not
      increase the steady-state firing rate, decrease afterhyperpolarization, or alter
      threshold potential. These results indicate that the basic cellular response of
      HMs to muscarinic receptors is excitatory, via a number of distinct mechanisms,
      and that this excitatory response will be largely preserved in rhythmically
      active brain stem slices.

PMID- 22858622
TI  - Invited editorial on "Lung volume and upper airway collapsibility: what does it
      tell us about pathogenic mechanisms?".

PMID- 22858621
TI  - Increased oxidative stress and anaerobic energy release, but blunted Thr172
      AMPKalpha phosphorylation, in response to sprint exercise in severe acute hypoxia
      in humans.
AB  - AMP-activated protein kinase (AMPK) is a major mediator of the exercise response
      and a molecular target to improve insulin sensitivity. To determine if the
      anaerobic component of the exercise response, which is exaggerated when sprint is
      performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)
      AMPKalpha phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate
      test) in normoxia and in severe acute hypoxia (inspired Po(2): 75 mmHg). Vastus
      lateralis muscle biopsies were obtained before and immediately after 30 and 120
      min postsprint. Mean power output and O(2) consumption were 6% and 37%,
      respectively, lower in hypoxia than in normoxia. O(2) deficit and muscle lactate
      accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal
      muscle and plasma proteins were increased after the sprint in hypoxia. Thr(172)
      AMPKalpha phosphorylation was increased by 3.1-fold 30 min after the sprint in
      normoxia. This effect was prevented by hypoxia. The NAD(+)-to-NADH.H(+) ratio was
      reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than
      in normoxia (P < 0.05), concomitant with 53% lower sirtuin 1 (SIRT1) protein
      levels after the sprint in hypoxia (P < 0.05). This could have led to lower liver
      kinase B1 (LKB1) activation by SIRT1 and, hence, blunted Thr(172)-AMPKalpha
      phosphorylation. Ser(485)-AMPKalpha(1)/Ser(491)-AMPKalpha(2) phosphorylation, a
      known negative regulating mechanism of Thr(172)-AMPKalpha phosphorylation, was
      increased by 60% immediately after the sprint in hypoxia, coincident with
      increased Thr(308)-Akt phosphorylation. Collectively, our results indicate that
      the signaling response to sprint exercise in human skeletal muscle is altered in
      severe acute hypoxia, which abrogated Thr(172)-AMPKalpha phosphorylation, likely
      due to lower LKB1 activation by SIRT1.

PMID- 22858623
TI  - Be sympathetic to your nervous system.

PMID- 22858625
TI  - New insights: does heat shock protein 70 mediate exercise-induced
      cardioprotection?

PMID- 22858624
TI  - Influence of exercise training on ischemic brain injury in type 1 diabetic rats.
AB  - While exercise training (ExT) appears to influence cerebrovascular function
      during type 1 diabetes (T1D), it is not clear whether this beneficial effect
      extends to protecting the brain from ischemia-induced brain injury. Thus our goal
      was to examine whether modest ExT could influence transient focal ischemia
      induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of
      cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four
      groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50
      mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we
      measured infarct volume in all groups of rats following right MCA occlusion for 2
      h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy
      was performed over the parietal cortex, and we measured responses of pial
      arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)
      dependent, and a NOS-independent agonist in all groups of rats. We found that
      sedentary diabetic rats had significantly larger total, cortical, and subcortical
      infarct volumes following ischemia-reperfusion than sedentary nondiabetic,
      nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary
      nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not
      alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In
      addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS
      independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened
      ischemic brain injury following middle cerebral artery occlusion and restored
      impaired eNOS- and nNOS-dependent vascular function. Since the incidence of
      ischemic stroke is increased during T1D, we suggest that our finding are
      significant in that modest ExT may be a viable preventative therapeutic approach
      to lessen ischemia-induced brain injury that may occur in T1D subjects.

PMID- 22858626
TI  - Adhesion of malignant mammary tumor cells MDA-MB-231 to microvessel wall
      increases microvascular permeability via degradation of endothelial surface
      glycocalyx.
AB  - To investigate the effect of tumor cell adhesion on microvascular permeability
      (P) in intact microvessels, we measured the adhesion rate of human mammary
      carcinoma MDA-MB-231, the hydraulic conductivity (L(p)), the P, and reflection
      coefficient (sigma) to albumin of the microvessels at the initial tumor cell
      adhesion and after ~45 min cell perfusion in the postcapillary venules of rat
      mesentery in vivo. Rats (Sprague-Dawley, 250-300 g) were anesthetized with
      pentobarbital sodium given subcutaneously. A midline incision was made in the
      abdominal wall, and the mesentery was gently taken out and arranged on the
      surface of a glass coverslip for the measurement. An individual postcapillary
      venule was perfused with cells at a rate of ~1 mm/s, which is the mean blood flow
      velocity in this type of microvessels. At the initial tumor cell adhesion, which
      was defined as one adherent cell in ~100- to 145-MUm vessel segment, L(p) was 1.5
      fold and P was 2.3-fold of their controls, and sigma decreased from 0.92 to 0.64;
      after ~45-min perfusion, the adhesion increased to ~5 adherent cells in ~100- to
      145-MUm vessel segment, while L(p) increased to 2.8-fold, P to 5.7-fold of their
      controls, and sigma decreased from 0.92 to 0.42. Combining these measured data
      with the predictions from a mathematical model for the interendothelial transport
      suggests that tumor cell adhesion to the microvessel wall degrades the
      endothelial surface glycocalyx (ESG) layer. This suggestion was confirmed by
      immunostaining of heparan sulfate of the ESG on the microvessel wall. Preserving
      of the ESG by a plasma glycoprotein orosomucoid decreased the P to albumin and
      reduced the tumor cell adhesion.

PMID- 22858627
TI  - Catecholamine-induced opening of intrapulmonary arteriovenous anastomoses in
      healthy humans at rest.
AB  - The mechanism or mechanisms that cause intrapulmonary arteriovenous anastomoses
      (IPAVA) to either open during exercise in subjects breathing room air and at rest
      when breathing hypoxic gas mixtures, or to close during exercise while breathing
      100% oxygen, remain unknown. During conditions when IPAVA are open, plasma
      epinephrine (EPI) and dopamine (DA) concentrations both increase, potentially
      representing a common mechanism. The purpose of this study was to determine
      whether EPI or DA infusions open IPAVA in resting subjects breathing room air
      and, subsequently, 100% oxygen. We hypothesized that these catecholamine
      infusions would open IPAVA. We performed saline-contrast echocardiography in nine
      subjects without a patent foramen ovale before and during serial EPI and DA
      infusions while breathing room air and then while breathing 100% oxygen. Bubble
      scores (0-5) were assigned based on the number and spatial distribution of
      bubbles in the left ventricle. Pulmonary artery systolic pressure (PASP) was
      estimated using Doppler ultrasound, while cardiac output (Q(C)) was measured
      using echocardiography. Bubble scores were significantly greater during EPI
      infusions of 80-320 ng.kg(-1).min(-1) compared with baseline when subjects
      breathed room air; however, bubble scores did not increase when they breathed
      100% oxygen. At comparable Q(C) and PASP, intravenous DA (16 MUg.kg(-1).min(-1))
      and EPI (40 ng.kg(-1).min(-1)) resulted in identical bubble scores. Subsequent
      studies revealed that beta-blockade did not prevent hypoxia-induced opening of
      IPAVA. We suggest that increases in Q(C) or PASP (or both) secondary to EPI or DA
      infusions open IPAVA in normoxia. The closing mechanism associated with breathing
      100% oxygen is independent from the opening mechanisms.

PMID- 22858628
TI  - Exercise delays neutrophil apoptosis by a G-CSF-dependent mechanism.
AB  - The aim of the study was to determine whether exercise affects neutrophil
      apoptosis and to characterize the underlying mechanisms. Using annexin V
      labeling, neutrophil apoptosis was measured using flow cytometry after various
      bouts of exercise (marathon run, concentric/eccentric treadmill exercise,
      moderate/intensive resistance training) and in vitro conditions. Similarly,
      apoptosis-related markers as death receptors/ligands and mitochondrial membrane
      potential were detected. Furthermore, concentrations of intracellular free
      calcium and glutathione were measured using spectrofluorometry. After both
      marathon run and intensive laboratory exercise tests, neutrophil apoptosis was
      delayed. Furthermore, neutrophils mitochondrial membrane potential and death
      receptor/ligand expression were not affected by exercise. Apoptosis delay was
      accompanied under some exercise conditions by enhanced intracellular calcium
      transients and decreased glutathione levels. A delay of spontaneous apoptosis in
      vitro could be induced by incubation of neutrophils in postexercise serum.
      Heating of postexercise serum abolished the apoptosis delaying effect. In vitro
      stimulation of resting neutrophils with granulocyte-colony-stimulating factor (G
      CSF) and C-reactive protein resulted in apoptosis delay too. Addition of anti-G
      CSF antibody to postexercise serum was also effective in reversing its apoptosis
      delaying effect. Exercise-induced mobilization of neutrophils is associated with
      a delay of apoptosis. This fundamental process seems to maintain exercise-induced
      neutrophilia and to contribute to the alerting and activation of the nonadaptive
      immune system known from other inflammatory conditions. An important
      extracellular trigger of apoptosis delay during exercise conditions seems to be G
      CSF; intracellular processes may include calcium and redox signaling.

PMID- 22858629
TI  - Decreased DNA fragmentation and apoptotic signaling in soleus muscle of
      hypertensive rats following 6 weeks of treadmill training.
AB  - Cardiovascular diseases such as hypertension are associated with a generalized
      skeletal myopathy including a proapoptotic phenotype. Current evidence suggests
      that exercise may alter apoptosis-related signaling in skeletal muscle; however,
      the effect of exercise on skeletal muscle DNA fragmentation and apoptotic
      signaling is unclear in hypertensive animals. Male normotensive Wistar Kyoto
      (WKY; n = 24) and spontaneously hypertensive rats (SHR; n = 24) were assigned to
      a sedentary (SED) condition or exercise (EX) consisting of progressive treadmill
      running 5 days/wk for 6 wks. Consistent with our previous work we found that
      soleus muscle of hypertensive animals had significantly higher DNA fragmentation
      (a hallmark of apoptosis), elevated proapoptotic factors (Bax, caspase-3
      activity), and lower antiapoptotic proteins (apoptosis repressor with caspase
      recruitment domain, Bcl-2, X-linked inhibitor of apoptosis protein) compared with
      normotensive rats. In addition, soleus muscle of hypertensive animals displayed
      myosin accumulation and fragmentation, had elevated cytosolic cytochrome c,
      second mitochondrial-derived activator of caspase (Smac), apoptosis inducing
      factor (AIF), and endonuclease G protein levels, higher nuclear AIF content, and
      greater muscle reactive oxygen species generation compared with normotensive
      animals. Interestingly, exercise training significantly lowered DNA fragmentation
      and myosin accumulation/fragmentation in soleus muscle of hypertensive rats.
      Furthermore, exercise training significantly reduced cytosolic levels of
      cytochrome c as well as cytosolic and nuclear AIF in soleus muscle of
      hypertensive animals. This beneficial response is likely due to exercise-mediated
      elevations in Bcl-2, heat shock protein 70, and manganese superoxide dismutase
      protein content, as well as reductions in Bax protein levels and the Bax-to-Bcl-2
      ratio. These results suggest that regular exercise training provides protection
      against skeletal muscle apoptosis by altering a number of apoptosis regulatory
      proteins and by influencing mitochondrial-mediated apoptotic signaling
      mechanisms.

PMID- 22858630
TI  - Exercise intensity typical of mountain climbing does not exacerbate acute
      mountain sickness in normobaric hypoxia.
AB  - Physical exertion is thought to exacerbate acute mountain sickness (AMS). In this
      prospective, randomized, crossover trial, we investigated whether moderate
      exercise worsens AMS in normobaric hypoxia (12% oxygen, equivalent to 4,500 m).
      Sixteen subjects were exposed to altitude twice: once with exercise [3 * 45 min
      within the first 4 h on a bicycle ergometer at 50% of their altitude-specific
      maximal workload (maximal oxygen uptake)], and once without. AMS was evaluated by
      the Lake Louise score and the AMS-C score of the Environmental Symptom
      Questionnaire. There was no significant difference in AMS between the exposures
      with and without exercise, neither after 5, 8, nor 18 h (incidence: 64 and 43%;
      LLS: 6.5 +/- 0.7 and 5.1 +/- 0.8; AMS-C score: 1.2 +/- 0.3 and 1.1 +/- 0.3 for
      exercise vs. rest at 18 h; all P > 0.05). Exercise decreased capillary Po(2)
      (from 36 +/- 1 Torr at rest to 31 +/- 1 Torr), capillary arterial oxygen
      saturation (from 72% at rest to 67 +/- 2%), and cerebral oxygen saturation (from
      49 +/- 2% at rest to 42 +/- 1%, as assessed by near-infrared spectroscopy; P <
      0.05), and increased ventilation (capillary Pco(2) 27 +/- 1 Torr; P < 0.05).
      After exercise, the increase in ventilation persisted for several hours and was
      associated with similar levels of capillary and cerebral oxygenation at the
      exercise and rest day. We conclude that moderate exercise at ~50% maximal oxygen
      uptake does not increase AMS in normobaric hypoxia. These data do not exclude
      that considerably higher exercise intensities exacerbate AMS.

PMID- 22858632
TI  - Photodynamic activity of viral nanoparticles conjugated with C60.
AB  - The development of viral nanoparticles (VNP) displaying multiple copies of the
      buckyball (C(60)) and their photodynamic activity is described. VNP-C(60)
      conjugates were assembled using click chemistry. Cell uptake and cell killing
      using white light therapy and a prostate cancer cell line is demonstrated.

PMID- 22858633
TI  - The SNARE protein SYP71 expressed in vascular tissues is involved in symbiotic
      nitrogen fixation in Lotus japonicus nodules.
AB  - Soluble N-Ethylmaleimide Sensitive Factor Attachment Protein Receptor (SNARE)
      proteins are crucial for signal transduction and development in plants. Here, we
      investigate a Lotus japonicus symbiotic mutant defective in one of the SNARE
      proteins. When in symbiosis with rhizobia, the growth of the mutant was retarded
      compared with that of the wild-type plant. Although the mutant formed nodules,
      these exhibited lower nitrogen fixation activity than the wild type. The rhizobia
      were able to invade nodule cells, but enlarged symbiosomes were observed in the
      infected cells. The causal gene, designated LjSYP71 (for L. japonicus syntaxin of
      plants71), was identified by map-based cloning and shown to encode a Qc-SNARE
      protein homologous to Arabidopsis (Arabidopsis thaliana) SYP71. LjSYP71 was
      expressed ubiquitously in shoot, roots, and nodules, and transcripts were
      detected in the vascular tissues. In the mutant, no other visible defects in
      plant morphology were observed. Furthermore, in the presence of combined
      nitrogen, the mutant plant grew almost as well as the wild type. These results
      suggest that the vascular tissues expressing LjSYP71 play a pivotal role in
      symbiotic nitrogen fixation in L. japonicus nodules.

PMID- 22858634
TI  - Positive regulation of psbA gene expression by cis-encoded antisense RNAs in
      Synechocystis sp. PCC 6803.
AB  - The D1 protein of photosystem II in the thylakoid membrane of photosynthetic
      organisms is encoded by psbA genes, which in cyanobacteria occur in the form of a
      small gene family. Light-dependent up-regulation of psbA gene expression is
      crucial to ensure the proper replacement of the D1 protein. To gain a high level
      of gene expression, psbA transcription can be enhanced by several orders of
      magnitude. Recent transcriptome analyses demonstrated a high number of cis
      encoded antisense RNAs (asRNAs) in bacteria, but very little is known about their
      possible functions. Here, we show the presence of two cis-encoded asRNAs (PsbA2R
      and PsbA3R) of psbA2 and psbA3 from Synechocystis sp. PCC 6803. These asRNAs are
      located in the 5' untranslated region of psbA2 and psbA3 genes. Their expression
      becomes up-regulated by light and down-regulated by darkness, similar to their
      target mRNAs. In the PsbA2R-suppressing strain [PsbA2R(-)], the amount of psbA2
      mRNA was only about 50% compared with the control strain. Likewise, we identified
      a 15% lowered activity of photosystem II and a reduced amount of the D1 protein
      in PsbA2R(-) compared with the control strain. The function of PsbA2R in the
      stabilization of psbA2 mRNA was shown from in vitro RNase E assay when the AU box
      and the ribosome-binding site in the 5' untranslated region of psbA2 mRNA were
      both covered by PsbA2R. These results add another layer of complexity to the
      mechanisms that contribute to psbA gene expression and show PsbA2R as a
      positively acting factor to achieve a maximum level of D1 synthesis.

PMID- 22858635
TI  - A chimeric arabinogalactan protein promotes somatic embryogenesis in cotton cell
      culture.
AB  - Arabinogalactan proteins (AGPs) are a family of extracellular plant proteoglycans
      implicated in many aspects of plant growth and development, including in vitro
      somatic embryogenesis (SE). We found that specific AGPs were produced by cotton
      (Gossypium hirsutum) calli undergoing SE and that when these AGPs were isolated
      and incorporated into tissue culture medium, cotton SE was promoted. When the
      AGPs were partly or fully deglycosylated, SE-promoting activity was not
      diminished. Testing of AGPs separated by reverse-phase high-performance liquid
      chromatography revealed that the SE-promoting activity resided in a hydrophobic
      fraction. We cloned a full-length complementary DNA (cotton PHYTOCYANIN-LIKE
      ARABINOGALACTAN-PROTEIN1 [GhPLA1]) that encoded the protein backbone of an AGP in
      the active fraction. It has a chimeric structure comprising an amino-terminal
      signal sequence, a phytocyanin-like domain, an AGP-like domain, and a hydrophobic
      carboxyl-terminal domain. Recombinant production of GhPLA1 in tobacco (Nicotiana
      tabacum) cells enabled us to purify and analyze a single glycosylated AGP and to
      demonstrate that this chimeric AGP promotes cotton SE. Furthermore, the
      nonglycosylated phytocyanin-like domain from GhPLA1, which was bacterially
      produced, also promoted SE, indicating that the glycosylated AGP domain was
      unnecessary for in vitro activity.

PMID- 22858637
TI  - Is trypanocidal drug resistance a threat for livestock health and production in
      endemic areas? Food for thoughts from Sahelian goats infected by Trypanosoma
      vivax in Bobo Dioulasso (Burkina Faso).
AB  - Trypanocidal drug resistance is unanimously recognized as a threat for livestock
      production in regions where the prevalence of trypanosomosis is high. To assess
      the impact of the disease and the effect of drug resistance on the health of
      small ruminants, twelve Trypanosoma vivax isolates collected in 6 villages in the
      vicinity of Bobo Dioulasso (Burkina Faso) were injected into 12 groups of 5
      Sahelian goats, two being treated with 3.5mg/kg body weight diminazene aceturate
      (DA), two with 0.5mg/kg body weight isometamidium chloride (ISM) and one left
      untreated as control. A monitoring was performed every 5 days for 100 days to
      evaluate the parasitaemia by buffy coat examination, the hematocrit and the body
      weight. Among the 12 groups, 6 were additionally monitored using a trypanosome
      specific 18S-PCR-RFLP every 5 days from day 30 to day 100 to verify the complete
      clearance of the parasites from the blood of the hosts. In six groups of goats,
      trypanosomes disappeared completely after treatment, five groups showed relapses
      in at least one goat treated with ISM and one group showed relapses in one goat
      treated with DA and one with ISM. For the 6 groups that were screened both using
      microscopic examination and trypanosome specific 18S-PCR-RFLP, the following
      results were observed: for the groups treated with DA, no relapses by microscopic
      examination and 83.3% (10/12) using the 18S-PCR-RFLP. For the groups treated with
      ISM, 25% (3/12) relapses by microscopic examination and 83.3% with the 18S-PCR
      RFLP (10/12). The evolution of the PCV and the weight during the observation
      period from relapsing (either by microscopical examination or by 18S-PCR-RFLP
      diagnosis) and non relapsing animals were compared. The relative average PCV in
      goats that relapsed microscopically, decreased significantly more than in non
      relapsing goats. This difference was not significant when relapses were detected
      using the trypanosome specific 18S-PCR-RFLP. This indicates that only the animals
      with the highest parasitaemia suffered from the infection. Relapses after
      treatment where the host controls the parasitaemia to a level below the
      sensitivity of the microscopical examination do not affect body weight nor PCV.

PMID- 22858636
TI  - Functional assessment of the Medicago truncatula NIP/LATD protein demonstrates
      that it is a high-affinity nitrate transporter.
AB  - The Medicago truncatula NIP/LATD (for Numerous Infections and
      Polyphenolics/Lateral root-organ Defective) gene encodes a protein found in a
      clade of nitrate transporters within the large NRT1(PTR) family that also encodes
      transporters of dipeptides and tripeptides, dicarboxylates, auxin, and abscisic
      acid. Of the NRT1(PTR) members known to transport nitrate, most are low-affinity
      transporters. Here, we show that M. truncatula nip/latd mutants are more
      defective in their lateral root responses to nitrate provided at low (250 MUm)
      concentrations than at higher (5 mm) concentrations; however, nitrate uptake
      experiments showed no discernible differences in uptake in the mutants.
      Heterologous expression experiments showed that MtNIP/LATD encodes a nitrate
      transporter: expression in Xenopus laevis oocytes conferred upon the oocytes the
      ability to take up nitrate from the medium with high affinity, and expression of
      MtNIP/LATD in an Arabidopsis chl1(nrt1.1) mutant rescued the chlorate
      susceptibility phenotype. X. laevis oocytes expressing mutant Mtnip-1 and Mtlatd
      were unable to take up nitrate from the medium, but oocytes expressing the less
      severe Mtnip-3 allele were proficient in nitrate transport. M. truncatula
      nip/latd mutants have pleiotropic defects in nodulation and root architecture.
      Expression of the Arabidopsis NRT1.1 gene in mutant Mtnip-1 roots partially
      rescued Mtnip-1 for root architecture defects but not for nodulation defects.
      This suggests that the spectrum of activities inherent in AtNRT1.1 is different
      from that possessed by MtNIP/LATD, but it could also reflect stability
      differences of each protein in M. truncatula. Collectively, the data show that
      MtNIP/LATD is a high-affinity nitrate transporter and suggest that it could have
      another function.

PMID- 22858638
TI  - Microhabitat preference of Anisakis simplex in three salmonid species:
      immunological implications.
AB  - Three salmonid fish species, Oncorhynchus mykiss, Salmo salar and Salmo trutta,
      were infected experimentally with the parasitic nematode Anisakis simplex (A.
      simplex) and the difference between in vivo behaviour of the nematode in the
      three fish species was investigated. Infection success rate differed between
      species. S. salar (Baltic salmon) showed the highest number of successfully
      established nematodes, whereas S. trutta (brown trout) and O. mykiss (rainbow
      trout) had a higher natural resistance. Microhabitat selection of nematodes
      differed according to fish species. In brown trout, A. simplex larvae were
      attached to the digestive tract (stomach, pyloric caeca, intestine), while the
      majority of larvae found in rainbow trout were located between the pyloric caeca.
      In Baltic salmon, nematodes were dispersed in and on spleen, head kidney, liver,
      swim bladder and musculature. Encapsulation and inflammatory cellular reactions
      differed accordingly. Histopathological and immunohistochemical studies using
      monoclonal antibodies raised against salmonid IgM, CD8 and MHCII were performed
      to detect the presence of immune cells around the infecting nematodes. None of
      the three fish species showed positive reactions for IgM-bearing cells in the
      inflammatory tissue connected with nematodes. CD8+ cells were detected in all
      three species and MHCII-bearing cells were found associated with encapsulated A.
      simplex in rainbow trout and brown trout, but not in Baltic salmon.
      Physiological, immunological and pathological implications of microhabitat
      differences are discussed.

PMID- 22858639
TI  - Comparative serum biochemical changes induced by experimental infection of T.
      brucei and T. congolense in pigs.
AB  - A comparative evaluation of the serum biochemical parameters was carried out in
      groups of young pigs aged 3-5 months experimentally infected with single
      infection of Trypanosoma brucei, Trypanosoma congolense, and a mixed infection of
      the two species. All the parameters studied (alanine amino transferase, aspartate
      amino transferase, albumin, globulin, cholesterol and creatinine) with the
      exception of total protein and urea varied significantly (p<0.05) between the
      infected groups and uninfected control group. Serum concentrations of alanine
      amino transferase, aspartate amino transferase, creatinine and globulin were
      increased whereas albumin and cholesterol decreased, except for the T. congolense
      group that had similar cholesterol levels as the control group. There was no
      significant variation (p>0.05) in the parameters within the infected groups
      except that creatinine was elevated in the T. brucei group. Administration of
      diminazene aceturate by day 42 PI restored alanine amino transferase, aspartate
      amino transferase and albumin to normal values unlike the other parameters. It
      was thus concluded that trypanosome infection in pigs could lead to some
      significant alterations in the serum biochemical values and that this was neither
      influenced by individual parasite species nor their mixed infection.

PMID- 22858640
TI  - Gamma ray attenuation in the soils of Northern Ireland, with special reference to
      peat.
AB  - This study considers gamma ray attenuation in relation to the soils and bedrock
      of Northern Ireland using simple theory and data from a high resolution airborne
      survey. The bedrock is considered as a source of radiogenic material acting as
      parent to the soil. Attenuation in the near-surface is then controlled by water
      content in conjunction with the porosity and density of the soil cover. The Total
      Count radiometric data together with 1:250 k mapping of the soils and bedrock of
      Northern Ireland are used to perform statistical analyses emphasising the nature
      of the low count behaviour. Estimations of the bedrock response characteristics
      are improved by excluding areas covered by low count soils (organic/humic).
      Equally, estimations of soil response characteristics are improved by excluding
      areas underlain by low count bedrock (basalt). When the spatial characteristics
      of the soil-classified data are examined in detail, the low values form spatially
      coherent zones (natural clusters) that can potentially be interpreted as areas of
      increased water content for each soil type. As predicted by theory, the highest
      attenuation factors are associated with the three organic soil types studied
      here. Peat, in particular, is remarkably skewed to low count behaviour in its
      radiometric response. Two detailed studies of blanket bogs reveal the extent to
      which peat may be mapped by its radiometric response while the intra-peat
      variations in the observed response may indicate areas of thin cover together
      with areas of increased water content.

PMID- 22858641
TI  - Update and improvement of the global krypton-85 emission inventory.
AB  - Krypton-85 is mainly produced in nuclear reactors by fission of uranium and
      plutonium and released during chopping and dissolution of spent fuel rods in
      nuclear reprocessing facilities. As noble gas it is suited as a passive tracer
      for evaluation of atmospheric transport models. Furthermore, research is ongoing
      to assess its quality as an indicator for clandestine reprocessing activities.
      This paper continues previous efforts to compile a comprehensive historic
      emission inventory for krypton-85. Reprocessing facilities are the by far largest
      emitters of krypton-85. Information on sources and calculations used to derive
      the annual krypton-85 emission is provided for all known reprocessing facilities
      in the world. In addition, the emission characteristics of two plants, Tokai
      (Japan) and La Hague (France), are analysed in detail using emission data with
      high temporal resolution. Other types of krypton-85 sources are power reactors,
      naval reactors and isotope production facilities. These sources contribute only
      little or negligible amounts of krypton-85 compared to the large reprocessing
      facilities. Taking the decay of krypton-85 into account, the global atmospheric
      inventory is estimated to about 5500 PBq at the end of 2009. The correctness if
      the inventory has been proven by meteorological simulations and its error is
      assumed to be in the range of a few percent.

PMID- 22858642
TI  - 210Po/210Pb dynamics in relation to zooplankton biomass and trophic conditions
      during an annual cycle in northwestern Mediterranean coastal waters.
AB  - Monthly sampling in northwestern Mediterranean coastal waters was undertaken to
      better understand the relationship between zooplankton biomass and the cycling of
      the natural radionuclide (210)Po/(210)Pb pair during a one-year period (October
      1995-November 1996). In conjunction with mesozooplankton collections and
      (210)Po/(210)Pb measurements in seawater, zooplankton and their fecal pellets,
      the biochemical composition of particulate organic matter (POM) was also examined
      at three depths (0, 20 and 50 m) as an indicator of trophic conditions. During
      May 1996, a strong zooplankton "bloom" was observed which was preceded by a
      prolonged increase in POM (protein + carbohydrates + lipids) starting at the end
      of March, and further demonstrated by a concomitant increase in the concentration
      of smaller particles, two features that are typical of mesotrophic waters.
      Simultaneous measurements of (210)Po in sea water and zooplankton showed an
      inverse trend between these two parameters during the sampling period, with the
      two lowest (210)Po concentrations in the dissolved phase of seawater coincident
      with the highest radionuclide concentrations in the zooplankton; however, this
      apparent relationship was not statistically significant over the entire year.
      Freshly excreted mesozooplankton and salp fecal pellets, which have been strongly
      implicated in the removal and downward transport of these radionuclides from the
      upper water column, contained (210)Po and (210)Pb levels ranging from 175 to 878
      and 7.5-486 Bq kg(-1) dry weight, respectively. Salp pellets contained 5 and 10
      times more (210)Po and (210)Pb than in fecal pellets produced by mixed
      zooplankton, a finding most likely related to their different feeding strategies.
      During the zooplankton biomass peak observed in May, the (210)Po concentration in
      zooplankton was at a minimum; however, in contrast to what has been reported to
      occur in some open sea oligotrophic waters, over the year no statistically
      significant inverse relationship was found between zooplankton biomass and
      (210)Po concentration in zooplankton. This observation may have resulted from the
      general lack of very low biomass concentrations (<1 mg m(-3)) measured in these
      coastal waters, biomass levels which commonly occur in open ocean oligotrophic
      regions.

PMID- 22858644
TI  - Characterization of a monoclonal antibody, Namu mAb, which reacts to the
      subventricular zone in mouse brain.
AB  - The lateral ventricle in adult mammalian brain is widely acknowledged as one of
      the areas that undifferentiated neural cells such as neural stem cells and neural
      progenitor cells inhabit. However, immunological aspects of neural stem cells in
      the lateral ventricle are still under debate. Here, we report the generation and
      characterization of a novel monoclonal antibody (mAb), called Namu mAb, which
      stains the subventricular zone in the lateral ventricle of adult mouse brain.
      Namu mAb reacted to the cells in the subventricular zone and never reacted to
      differentiated neural cells such as neurons and glial cells such as astrocytes
      and oligodendrocytes. Its reaction pattern for the subventricular zone and the
      neurospheres was similar to that of Nestin and glial fibrillary acidic protein
      mAbs. Namu mAb recognition molecule, Namu antigen, was a 50 kDa protein present
      in the cytoplasmic fraction of mouse brain, and its expression was clearly
      observed in neurospheres cultured in the presence of epidermal growth factor, but
      it was never or only weakly induced in the presence of basic fibroblast growth
      factor or leukemia inhibitory factor. Collectively, it is concluded that Namu mAb
      specifically reacts to undifferentiated neural cells in mouse brain.

PMID- 22858645
TI  - Appraisal of a copresent observer as supportive activates the left inferior
      parietal lobule:  a near-infrared spectroscopy study using a driving video game.
AB  - The role of the presence of others in a social context has been debated widely.
      Although the importance of mutual cognitive functions between performer and
      observer is generally accepted, little is known about the neural correlates of
      paired performers and observers themselves. In this near-infrared spectroscopy
      (NIRS) study we measured the activation in the bilateral inferior parietal lobule
      (IPL) when driver-observer pairs of participants performed a driving video game
      task. The performer's task was to drive from start to goal using a default route
      map, while their partner observed the performance. According to the performer's
      subjective appraisal of the copresent observer obtained after the driving task,
      the pairs were divided into three groups: supportive, nonsupportive, and neutral.
      The driving time, error, and tension score did not show significant differences
      between the three groups. However, NIRS data of performers in the supportive
      group showed significantly higher activation in the left IPL than those in the
      nonsupportive group, but not in the right IPL. NIRS data of observers in the
      concerned two groups did not show significant differences bilaterally in IPL.
      These results suggest that the left IPL distinctively responds according to a
      performer's cognitive appraisal of a copresent observer.

PMID- 22858646
TI  - Developing guidance for checking pregnancy status in adolescent girls before
      surgical, radiological or other procedures.

PMID- 22858643
TI  - ROCKs cause SHP-wrecks and broken hearts.
AB  - During embryogenesis, the heart is one of the first organs to develop. Its
      formation requires a complex combination of migration of cardiac precursors to
      the ventral midline coupled with the fusion of these cardiogenic fields and
      subsequent cellular reorganization to form a linear heart tube. A finely
      controlled choreography of cell proliferation, adhesion, contraction and movement
      drives the heart tube to loop and subsequently septate to form the four-chambered
      mammalian heart we are familiar with. Defining how this plethora of cellular
      processes is controlled both spatially and temporally is a scientific feat that
      has fascinated researchers for decades. Unfortunately, the complex nature of this
      organ's development also makes it a prime target for mutation-induced
      malformation, as evidenced by the multitude of prevalent congenital heart
      disorders identified that afflict up to 1% of the population.

PMID- 22858647
TI  - Complex regional pain syndrome following immunisation.
AB  - Complex regional pain syndrome type 1 (CRPS-1) is a clinical syndrome that
      affects one or more extremities and is characterised by persistent pain
      disproportionate to any inciting event, and at least one sign of autonomic
      dysfunction in the affected limb(s). The pathogenesis of this syndrome is poorly
      understood, but its onset is often precipitated by a physical injury, such as
      minor trauma, fracture, infection or a surgical procedure. In the literature,
      there are reports of CRPS-1 following immunisation with rubella and hepatitis B
      vaccines. Here we present a case series of CRPS-1 following immunisation in
      adolescents, with either diphtheria-tetanus-acellular pertussis (1 case), or
      human papillomavirus vaccines (4 cases). Enhanced awareness of this syndrome and
      its potential to occur following immunisation in the paediatric population is
      vital to the prompt and effective management of this condition.

PMID- 22858648
TI  - One-dimensional hybrid nanostructures: synthesis via layer-by-layer assembly and
      applications.
AB  - Assembly techniques are being intensely sought for preparing nanocomposites with
      tunable compositions and structures. Compared to other assembly techniques, the
      layer-by-layer (LBL) technique, which is based on the electrostatic attraction
      between oppositely charged species, provides a simple, versatile and powerful
      method to synthesize various types of one-dimensional (1D) hybrid nanostructures.
      In this review, we begin with the developments in the LBL synthesis of
      nanocomposites, with a focus on our recent results for synthesizing 1D hybrid
      nanostructures via LBL assembly. Compared to previous LBL processes, we conducted
      the in situ reaction on the surface of 1D nanostructures via electrostatic
      attraction between oppositely charged 1D nanostructures and ions in the solution
      in an attempt to produce 1D hybrid nanostructures. Moreover, these core-shell
      nanostructures can be transformed into nanotubes by the removal of the templates.
      The as-synthesized 1D hybrid nanostructures and nanotubes with tunable
      composition exhibited enhanced performance for various applications such as gas
      sensors, lithium-ion batteries and cellular imaging.

PMID- 22858649
TI  - Bufalin increases sensitivity to AKT/mTOR-induced autophagic cell death in SK-HEP
      1 human hepatocellular carcinoma cells.
AB  - Bufalin is the major component of Chan-Su (a traditional Chinese medicine, TCM)
      extracts from the venom of Bufo bufo gargarizan. In the present study, we
      investigated the pharmacological mechanisms of cell cycle arrest and autophagic
      cell death induced by bufalin in SK-HEP-1 human hepatocellular carcinoma cells in
      vitro. Bufalin inhibited cell survival by MTT assay and increased cell death by
      trypan blue exclusion assay in a concentration-dependent manner. In addition,
      bufalin induced G2/M phase arrest by reducing CDK1 activity. Bufalin triggered
      DNA fragmentation and apoptotic cell death in SK-HEP-1 cells by DNA gel
      electrophoresis, TUNEL and caspase-3 activity assay, while bufalin induced
      autophagic cell death by double-membrane vacuoles (transmission electron
      microscopy, TEM), acidic vesicular organelles (acridine orange staining) and
      cleavage of microtubule-associated protein 1 light chain 3 (LC3). Protein
      expression levels of cyclin A and B, CDK1, phospho-CDK1 (Thr161), Cdc25c, phospho
      Cdc25c (Ser198), phospho-AKT (Thr308), phospho-AKT (Ser473), phospho-mTOR
      (Ser2481) were downregulated. In contrast, protein expression levels of the Chk1,
      Wee1, LC3-II, Beclin-1, Atg 5, Atg 7 and Atg 12 were upregulated in SK-HEP-1
      cells after bufalin treatment. Inhibition of autophagy by 3-methyladenine (an
      inhibitor of class III phosphatidylinositol-3 kinase; 3-MA) or bafilomycin A1 (an
      inhibitor of the vacuolar proton pump of lysosomes and endosomes) reduced the
      effect of bufalin on cell viability and enhanced the effect of bufalin on
      apoptosis. In conclusion, bufalin triggered autophagic cell death and G2/M phase
      arrest through the AKT/mTOR signaling pathway in SK-HEP-1 cells. Our findings
      showed that bufalin may be potentially efficacious in the treatment of human
      hepatocellular carcinoma.

PMID- 22858650
TI  - On the armament and appearances of human myeloid-derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSC) have frequently been observed in patients
      with cancer. This heterogeneous population of myeloid cells can exert potent
      suppression of lymphocyte function and thereby poses a significant hurdle to
      natural or therapeutically induced anti-tumor immunity. On the other hand, the
      natural function of MDSC is not yet well understood and their role in infection,
      inflammation and autoimmune disease is still puzzling. Understanding MDSC biology
      will provide the tools necessary for therapeutic targeting of this population,
      but also permit exploitation of their strong tolerogenic function in the
      treatment of inflammatory conditions and the prevention of graft rejection.

PMID- 22858651
TI  - Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic
      high-resolution image-based three-dimensional model.
AB  - Osteocytes play a pivotal role in the regulation of skeletal mass. Osteocyte
      processes are thought to sense the flow of interstitial fluid that is driven
      through the osteocyte canaliculi by mechanical stimuli placed upon bone, but how
      this flow elicits a cellular response is virtually unknown. Modern theoretical
      models assume that osteocyte canaliculi contain ultrastructural features that
      amplify the fluid flow-derived mechanical signal. Unfortunately the calcified
      bone matrix has considerably hampered studies on the osteocyte process within its
      canaliculus. Using one of the few ultra high voltage electron microscopes (UHVEM)
      available worldwide, we applied UHVEM tomography at 2 MeV to reconstruct unique
      three-dimensional images of osteocyte canaliculi in 1 MUm sections of human bone.
      A realistic three-dimensional image-based model of a single canaliculus was
      constructed, and the fluid dynamics of a Newtonian fluid flow within the
      canaliculus was analyzed. We created virtual 2.2 nm thick sections through a
      canaliculus and found that traditional TEM techniques create a false impression
      that osteocyte processes are directly attached to the canalicular wall. The
      canalicular wall had a highly irregular surface and contained protruding
      axisymmetric structures similar in size and shape to collagen fibrils. We also
      found that the microscopic surface roughness of the canalicular wall strongly
      influenced the fluid flow profiles, whereby highly inhomogeneous flow patterns
      emerged. These inhomogeneous flow patterns may induce deformation of cytoskeletal
      elements in the osteocyte process, thereby amplifying mechanical signals. Based
      on these observations, new and realistic models can be developed that will
      significantly enhance our understanding of the process of mechanotransduction in
      bone.

PMID- 22858653
TI  - Summary of the II Brazilian Guideline update on Acute Heart Failure 2009/2011.
AB  - In the past two years we observed several changes in the diagnostic and
      therapeutic approach of patients with acute heart failure (acute HF), which led
      us to the need of performing a summary update of the II Brazilian Guidelines on
      Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart
      was simplified and the role of clinical assessment and echocardiography was
      enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic
      echocardiography gained prominence as an aid to define this condition in patients
      with acute HF in the emergency room. In the prognostic evaluation, the role of
      biomarkers was better established and the criteria and prognostic value of the
      cardiorenal syndrome was better defined. The therapeutic approach flowcharts were
      revised, and are now simpler and more objective. Among the advances in drug
      therapy, the safety and importance of the maintenance or introduction of beta
      blockers in the admission treatment are highlighted. Anticoagulation, according
      to new evidence, gained a wider range of indications. The presentation
      hemodynamic models of acute pulmonary edema were well established, with their
      different therapeutic approaches, as well as new levels of indication and
      evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical
      lesions and heart transplantation were reviewed and updated. This update
      strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated
      and refreshed. All clinical cardiologists who deal with patients with acute HF
      will find, in the guidelines and its summary, important tools to help them with
      the clinical practice for better diagnosis and treatment of their patients.

PMID- 22858654
TI  - Physical exercise and microRNAs: new frontiers in heart failure.
AB  - Although the impact of exercise on survival of patients with heart failure has
      been recently questioned, exercise training improves quality of life, functional
      capacity, inflammation, endothelial and autonomic function. In recent years,
      interest has increased regarding a group of small non-protein coding RNAs called
      microRNAs. Studies have shown that the expression of these molecules changes in
      several pathological conditions, such as myocardial infarction, myocardial
      ischemia and heart failure, and when clinical improvement occurs, they seem to
      normalize. With the potential for practical applicability, markers that may be
      useful in diagnostic and prognostic assessment of heart failure have been
      identified, such as miR-423-5p. In addition, results of experimental studies have
      indicated that there are potential therapeutic effects of microRNAs. MicroRNAs
      are involved in the regulation of gene expression during fetal development and in
      adult individuals, increasing or decreasing in the heart in response to
      physiological stress, injury or hemodynamic overload. Thus, the study of the
      behavior of these molecules in physical exercise has brought important
      information about the effects of this therapeutic modality and represents a new
      era in the understanding of heart failure. This review aims to integrate the
      evidence on microRNAs in heart failure with greater relevance in the study of
      physical exercise.

PMID- 22858655
TI  - Evaluation of noncompaction cardiomyopathy by modern echocardiographic methods.

PMID- 22858656
TI  - Heart failure: the scenario is still worrying!

PMID- 22858657
TI  - Case 4/2012--25-year-old man with obstructive fibroma in right ventricular
      outflow tract.

PMID- 22858652
TI  - Limitations in anti-obesity drug development: the critical role of hunger
      promoting neurons.
AB  - Current anti-obesity drugs aim to reduce food intake by either curbing appetite
      or suppressing the craving for food. However, many of these agents have been
      associated with severe psychiatric and/or cardiovascular side effects,
      highlighting the need for alternative therapeutic strategies. Emerging knowledge
      on the role of the hypothalamus in enabling the central nervous system to adapt
      to the changing environment - by managing peripheral tissue output and by
      regulating higher brain functions - may facilitate the discovery of new agents
      that are more effective and have an acceptable benefit-risk profile. Targeting
      the molecular pathways that mediate the beneficial effects of calorie restriction
      and exercise may represent an alternative therapeutic approach for the treatment
      of chronic metabolic disorders such as obesity.

PMID- 22858658
TI  - Rare manifestation of acute pulmonary edema associated with acute lupus
      myocarditis.
AB  - Systemic Lupus Erythematosus (SLE) is the most common systemic autoimmune
      disease, occurring more frequently in women, usually aged between 16 and 55 years
      1, 2. Although classically the kidneys are the organs most affected in SLE,
      cardiopulmonary circulation and the heart may also be affected significantly 3.
      In this context, the occurrence of acute pulmonary edema associated with lupus
      myocarditis is rare and specific immunosuppressive therapy remains unclear.

PMID- 22858659
TI  - Transient lymphadenopathy secondary to nephrotic syndrome.
AB  - Mediastinal lymphadenomegaly secondary to hypervolemia is an underdiagnosed
      tomographic finding. Herein we describe, in a patient with normal cardiac
      function, findings of pulmonary congestion associated to lymph node enlargement.
      The nephrotic syndrome causing hypoalbuminemia, low plasma colloid osmotic
      pressure and augmented transcapillary fluid leakage was the probable cause of the
      radiological findings.

PMID- 22858660
TI  - Risk scores in valvular heart disease interventions.
AB  - The risk scores used as assistance agents in valve diseases are validated
      worldwide; however, the data are not homogeneous. The epidemiological
      characteristics of each population require local validation of these risk tools.
      The percutaneous valve replacement, which is a reality in valvular diseases
      (especially aortic stenosis), is indicated for patients with high or prohibitive
      surgical risk. Studies with this new treatment strategy use risk scores as
      criteria for inclusion and there are few studies that use such tools as
      predictors of risk. The risk scores, after due validation in their relevant
      populations, are combined with clinical practice (individualization of conduct)
      in the definition of the conduct to be adopted in the clinical practice of
      valvular heart disease.

PMID- 22858661
TI  - Semisynthetic peptide-lipase conjugates for improved biotransformations.
AB  - An efficient chemoselective method for the creation of semisynthetic lipases by
      site-specific incorporation of tailor-made peptides on the lipase-lid site was
      developed. These new enzymes showed excellent improved specificity and regio- or
      enantioselectivity in different biotransformations.

PMID- 22858662
TI  - Development of a distributed air pollutant dry deposition modeling framework.
AB  - A distributed air pollutant dry deposition modeling system was developed with a
      geographic information system (GIS) to enhance the functionality of i-Tree Eco (i
      Tree, 2011). With the developed system, temperature, leaf area index (LAI) and
      air pollutant concentration in a spatially distributed form can be estimated, and
      based on these and other input variables, dry deposition of carbon monoxide (CO),
      nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and particulate matter less
      than 10 microns (PM10) to trees can be spatially quantified. Employing nationally
      available road network, traffic volume, air pollutant emission/measurement and
      meteorological data, the developed system provides a framework for the U.S. city
      managers to identify spatial patterns of urban forest and locate potential areas
      for future urban forest planting and protection to improve air quality. To
      exhibit the usability of the framework, a case study was performed for July and
      August of 2005 in Baltimore, MD.

PMID- 22858663
TI  - Lowered N-terminal pro-B-type natriuretic peptide levels in response to treatment
      predict survival in dogs with symptomatic mitral valve disease.
AB  - OBJECTIVES: In humans with congestive heart failure (CHF), better outcome is
      correlated with lower natriuretic peptide (NP) levels after starting treatment
      and greater percentage reduction of NP levels. Therefore, the aim of this study
      was to determine the relationship between absolute and relative changes in N
      terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic
      peptide 31-67 (proANP 31-67) and overall cardiac survival in patients with
      symptomatic myxomatous mitral valve disease (MMVD). Furthermore, we sought to
      compare clinical and echocardiographic status of 12-month survivors and non
      survivors. ANIMALS, MATERIALS AND METHODS: 26 dogs with CHF due to MMVD. Initial
      NP levels, as well as absolute and percentage changes of follow-up NP levels
      (between 7 and 30 days after treatment start) and heart failure (HF) class were
      tested as potential predictors of overall cardiac survivorship. Additionally,
      various echocardiographic parameters, creatinine concentrations and furosemide
      doses were compared between 12-month survivors and non-survivors. RESULTS: Dogs
      with follow-up NT-proBNP level <965 pmol/l had a significantly longer overall
      cardiac survival than patients with NT-proBNP level >965 pmol/l (P = 0.03). Dogs
      in a higher HF class had a significantly (P = 0.03) higher probability of shorter
      survival independent of their NP levels. When dogs were grouped by 12-month
      survival, only follow-up NT-proBNP levels were significantly different between
      groups. CONCLUSIONS: HF class at presentation and NT-proBNP levels after
      initiating treatment are predictive of mortality in patients with symptomatic
      MMVD. ProANP 31-67 levels, percentage reduction in NPs levels, creatinine or urea
      concentration, echocardiographic parameters and furosemide dose did not predict
      outcome.

PMID- 22858664
TI  - Halogen bonding in solution: thermodynamics and applications.
AB  - Halogen bonds are noncovalent interactions in which covalently bound halogens act
      as electrophilic species. The utility of halogen bonding for controlling self
      assembly in the solid state is evident from a broad spectrum of applications in
      crystal engineering and materials science. Until recently, it has been less clear
      whether, and to what extent, halogen bonding could be employed to influence
      conformation, binding or reactivity in the solution phase. This tutorial review
      summarizes and interprets solution-phase thermodynamic data for halogen bonding
      interactions obtained over the past six decades and highlights emerging
      applications in molecular recognition, medicinal chemistry and catalysis.

PMID- 22858665
TI  - Octadecyltrimethoxysilane functionalized ZnO nanorods as a novel coating for
      solid-phase microextraction with strong hydrophobic surface.
AB  - In this paper, we have, for the first time, proposed an approach by combining
      self-assembled monolayers (SAMs) and nanomaterials (NMs) for the preparation of
      novel solid-phase microextraction (SPME) coatings. The self-assembly of
      octadecyltrimethoxysilane (OTMS) on the surface of ZnO nanorods (ZNRs) was
      selected as a model system to demonstrate the feasibility of this approach. The
      functionalization of OTMS on the surface of ZNRs was characterized and confirmed
      using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy
      (EDS). The OTMS-ZNRs coated fiber exhibited stronger hydrophobicity after
      functionalization, and its extraction efficiency for non-polar benzene homologues
      was increased by a factor of 1.5-3.6 when compared to a ZNRs fiber with almost
      identical thickness and facade. In contrast, the extraction efficiency of the
      OTMS-ZNRs coated fiber for polar aldehydes was 1.6-4.0-fold lower than that of
      the ZNRs coated fiber, further indicating its enhanced surface hydrophobicity.
      The OTMS-ZNRs coated fiber revealed a much higher capacity upon increasing the
      OTMS layer thickness to 5 MUm, leading to a factor of 12.0-13.4 and 1.8-2.5
      increase in extraction efficiency for the benzene homologues relative to a ZNRs
      coated fiber and a commercial PDMS fiber, respectively. The developed HS-SPME-GC
      method using the OTMS-ZNRs coated fiber was successfully applied to the
      determination of the benzene homologues in limnetic water samples with recovery
      ranging from 83 to 113% and relative standard deviations (RSDs) of less than 8%.

PMID- 22858667
TI  - Influence of 1H chemical shift assignments of the interface residues on structure
      determinations of homodimeric proteins.
AB  - Homodimeric proteins pose a difficulty for NMR structure determination because
      the degeneracy of the chemical shifts in the two identical monomers implies an
      ambiguity in all assignments of distance restraints. For homodimeric proteins,
      residues involved in the interface between two monomers provide essential
      intermolecular NOEs. The structure determination of homodimeric proteins hence
      relies strongly on chemical shift assignments of these interface residues. Our
      paper discusses the influence of the extent of (1)H chemical shift assignments of
      interface residues on the structure determinations of homodimeric proteins using
      the CYANA program. The results reveal that successful structure determinations of
      homodimeric proteins with automated NOE assignment depend on the percentage of
      assigned interface residues and that a high completeness of around 80-90% of the
      (1)H chemical shift assignment in the interface is needed for reliable NMR
      structure determinations of homodimeric proteins for which no experimental
      distinction between intra- and intermolecular NOEs, e.g. by filtered NOESY
      experiments, is available. Our results also show that RMSD and target function
      values are insufficient to judge the quality of homodimeric structures determined
      using automated NOE assignment. Structure determinations of homodimeric proteins
      by NMR using conventional NOESY experiments are thus possible but more
      challenging than for monomeric proteins.

PMID- 22858666
TI  - Evaluating the use of a continuous approximation for model-based quantification
      of pulsed chemical exchange saturation transfer (CEST).
AB  - Many potential clinical applications of chemical exchange saturation transfer
      (CEST) have been studied in recent years. However, due to various limitations
      such as specific absorption rate guidelines and scanner hardware constraints,
      most of the proposed applications have yet to be translated into routine
      diagnostic tools. Currently, pulsed CEST which uses multiple short pulses to
      perform the saturation is the only viable irradiation scheme for clinical
      translation. However, performing quantitative model-based analysis on pulsed CEST
      is time consuming because it is necessary to account for the time dependent
      amplitude of the saturation pulses. As a result, pulsed CEST is generally treated
      as continuous CEST by finding its equivalent average field or power.
      Nevertheless, theoretical analysis and simulations reveal that the resulting
      magnetization is different when the different irradiation schemes are applied. In
      this study, the quantification of important model parameters such as the amine
      proton exchange rate from a pulsed CEST experiment using quantitative model-based
      analyses were examined. Two model-based approaches were considered - discretized
      and continuous approximation to the time dependent RF irradiation pulses. The
      results showed that the discretized method was able to fit the experimental data
      substantially better than its continuous counterpart, but the smaller fitted
      error of the former did not translate to significantly better fit for the
      important model parameters. For quantification of the endogenous CEST effect,
      such as in amide proton transfer imaging, a model-based approach using the
      average power equivalent saturation can thus be used in place of the discretized
      approximation.

PMID- 22858668
TI  - Shearing of synovial fluid activates latent TGF-beta.
AB  - OBJECTIVE: TGF-beta is synthesized in an inactive latent complex that is unable
      to bind to membrane receptors, thus unable to induce a cellular biological
      response until it has been activated. In addition to activation by chemical
      mediators, recent studies have demonstrated that mechanical forces may activate
      latent TGF-betavia integrin-mediated cellular contractions, or mechanical
      shearing of blood serum. Since TGF-beta is present in synovial fluid in latent
      form, and since normal diarthrodial joint function produces fluid shear, this
      study tested the hypothesis that the native latent TGF-beta1 of synovial fluid
      can be activated by shearing. DESIGN: Synovial fluid from 26 bovine joints and
      three adult human joints was sheared at mean shear rates up to 4000 s(-1) for up
      to 15 h. RESULTS: Unsheared synovial fluid was found to contain high levels of
      latent TGF-beta1 (4.35 +/- 2.02 ng/mL bovine, 1.84 +/- 0.89 ng/mL human; mean +/-
      radius of 95% confidence interval) and low amounts (<0.05 ng/mL) of the active
      peptide. Synovial fluid concentrations of active TGF-beta1 increased
      monotonically with shear rate and shearing duration, reaching levels of 2.64 +/-
      1.22 ng/mL for bovine and 0.60 +/- 0.39 ng/mL for human synovial fluid. Following
      termination of shearing, there was no statistical change in these active levels
      over the next 8 h for either species, demonstrating long-term stability of the
      activated peptide. The unsheared control group continued to exhibit negligible
      levels of active TGF-beta1 at all times. CONCLUSIONS: Results confirmed the
      hypothesis of this study and suggest that shearing of synovial fluid might
      contribute an additional biosynthetic effect of mechanical loading of
      diarthrodial joints.

PMID- 22858670
TI  - Identifying source and formation altitudes of nitrates in drinking water from
      Reunion Island, France, using a multi-isotopic approach.
AB  - Nitrate concentrations, water isotopes (delta(2)H and delta(18)O(water)) and
      associated nitrate isotopes (delta(15)N(nitrate) and delta(18)O(nitrate)) from 10
      drinking water wells, 5 fresh water springs and the discharge from 3 wastewater
      treatment stations in Reunion Island, located in the Indian Ocean, were analysed.
      We used a multi isotopic approach to investigate the extent of nitrate
      contamination, nitrate formation altitude and source of nitrates in Reunion
      Island's principal aquifer. Water from these study sites contained between 0.1
      and 85.3 mg/L nitrate. delta(15)N(nitrate) values between +6 and +140/00
      suggested the main sources of contamination were animal and/or human waste,
      rather than inorganic (synthetic) fertilisers, infiltrating through the
      subsurface into the saturated zone, due to rainfall leaching of the unsaturated
      zone at various altitudes of precipitation. Based on delta(15)N(nitrate) values
      alone, it was not possible to distinguish between animal and human activities
      responsible for the contamination of each specific catchment. However, using a
      multi isotope approach (delta(18)O(water) and delta(15)N(nitrate)), it was
      possible to relate the average altitude of rainfall infiltration
      (delta(18)O(water)) associated with the nitrate contamination
      (delta(18)O(nitrate)). This relationship between land use, rainfall recharge
      altitude and isotopic composition (delta(15)N(nitrate) and delta(18)O(water))
      discriminated between the influences of human waste at lower (below 600 m
      elevation) or animal derived contamination (at elevations between 600 and 1300
      m). By further comparing the theoretical altitude of nitrate formation calculated
      by the delta(18)O(nitrate), it was possible to determine that only 5 out of 15
      fresh water wells and springs followed the conservative nitrate formation
      mechanism of 2/3delta(18)O(water)+1/3delta(18)O(air), to give nitrate formation
      altitudes which corresponded to land use activities.

PMID- 22858669
TI  - Structure-function relationships in osteoarthritic human hip joint articular
      cartilage.
AB  - OBJECTIVES: It is currently poorly known how different structural and
      compositional components in human articular cartilage are related to their
      specific functional properties at different stages of osteoarthritis (OA). The
      objective of this study was to characterize the structure-function relationships
      of articular cartilage obtained from osteoarthritic human hip joints. METHODS:
      Articular cartilage samples with their subchondral bone (n = 15) were harvested
      during hip replacement surgeries from human femoral necks. Stress-relaxation
      tests, Mankin scoring, spectroscopic and microscopic methods were used to
      determine the biomechanical properties, OA grade, and the composition and
      structure of the samples. In order to obtain the mechanical material parameters
      for the samples, a fibril-reinforced poroviscoelastic model was fitted to the
      experimental data obtained from the stress-relaxation experiments. RESULTS: The
      strain-dependent collagen network modulus (E(f)(epsilon)) and the collagen
      orientation angle exhibited a negative linear correlation (r = -0.65, P < 0.01),
      while the permeability strain-dependency factor (M) and the collagen content
      exhibited a positive linear correlation (r = 0.56, P < 0.05). The nonfibrillar
      matrix modulus (E(nf)) also exhibited a positive linear correlation with the
      proteoglycan content (r = 0.54, P < 0.05). CONCLUSION: The study suggests that
      increased collagen orientation angle during OA primarily impairs the collagen
      network and the tensile stiffness of cartilage in a strain-dependent manner,
      while the decreased collagen content in OA facilitates fluid flow out of the
      tissue especially at high compressive strains. Thus, the results provide
      interesting and important information of the structure-function relationships of
      human hip joint cartilage and mechanisms during the progression of OA.

PMID- 22858671
TI  - Transport and retention of fullerene (nC60) nanoparticles in unsaturated porous
      media: effects of solution chemistry and solid phase coating.
AB  - The retention and release of aqueous aggregates of fullerene nanoparticles
      (nC(60)) were studied under dynamic unsaturated conditions. Porous media
      containing nC(60) were taken through multiple drainage/imbibition
      (drying/wetting) cycles to explore the effects of solution conditions and solid
      surface modification on transport and ultimate fate in unsaturated porous media.
      In experiments conducted with NaCl as the background electrolyte, the retention
      of nC(60) during drainage was found to be negligibly small over a wide range of
      ionic strengths (I=0.2 to I=6 mM), significantly lower than the retention of
      titanium dioxide nanoparticles studied previously under similar conditions. In
      contrast, experiments conducted with CaCl(2) as the background electrolyte found
      that retention of nC(60) during drainage was significant at higher ionic
      strengths, particularly at the highest ionic strength studied (I=6 mM).
      Experiments examining the influence of dissolved natural organic matter on nC(60)
      retention in unsaturated media found no measurable impact on the transport. The
      effects of solid surface modification were examined by creating coatings that
      modified surface hydrophobicity and charge. Experiments found that a hydrophobic
      coating had no measurable impact on nC(60) retention, when compared with
      retention by unmodified media. In contrast, a porous medium with surfaces that
      were both hydrophobic and positively-charged retained 5-10 times more nC(60)
      during drainage than an unmodified porous medium. This result suggests that
      electrostatic interactions play a more important role than hydrophobic
      interactions in the transport and fate of nC(60) in the unsaturated zone. For all
      conditions where retention was observed, experiments found very little release or
      retained nC(60) after subsequent flushing with water, suggesting that once
      retained, the environmental mobility of nC(60) may be extremely limited.

PMID- 22858672
TI  - New insights into siRNA amplification and RNAi.
AB  - In the nematode Caenorhabditis elegans (C. elegans), gene inactivation by RNA
      interference can achieve remarkable potency due to the amplification of initial
      silencing triggers by RNA-dependent RNA polymerases (RdRPs). RdRPs catalyze the
      biogenesis of an abundant species of secondary small interfering RNAs (siRNAs)
      using the target mRNA as template. The interaction between primary siRNAs derived
      from the exogenous double-stranded RNA (dsRNA) trigger and the target mRNA is
      required for the recruitment of RdRPs. Other genetic requirements for RdRP
      activities have not been characterized. Recent studies have identified the RDE
      10/RDE-11 complex which interacts with the primary siRNA bound target mRNA and
      acts upstream of the RdRPs. rde-10 and rde-11 mutants show an RNAi defective
      phenotype because the biogenesis of secondary siRNAs is completely abolished. In
      addition, the RDE-10/RDE-11 complex plays a similar role in the endogenous RNAi
      pathway for the biogenesis of a subset of siRNAs targeting recently acquired,
      duplicated genes.

PMID- 22858674
TI  - RNA science and its applications-a look toward the future: Albany, NY USA,
      November 3-4, 2011.
AB  - On November 3-4, 2011, the Symposium RNA Science and its Applications: A look
      toward the Future was held at the University at Albany-SUNY in the capital of New
      York State. Unique to this Symposium's format were panel discussions following
      each of the four platform sessions: RNA Technological Innovation: Analysis,
      Delivery, Nanotechnologies, IT; Infectious and other diseases: The future of
      small molecule intervention; RNA Discovery and Innovation: Cell and Molecular
      Biology; and Cancer and Neurological Disease: The future of small RNAs as
      therapeutics and tools of investigation. The meeting was organized by Thomas
      Begley, Marlene Belfort, Daniele Fabris, Melinda Larsen, Pan T.X. Li, Albert
      Millis, Li Niu, David Shub, and Carla Theimer of The RNA Institute at University
      at Albany-SUNY, Paul F. Agris, Director, and Jennifer S. Montimurro, Program
      Manager.

PMID- 22858673
TI  - Translational repression of cyclin D3 by a stable G-quadruplex in its 5' UTR:
      implications for cell cycle regulation.
AB  - cyclin D3 (CCND3) is one of the three D-type cyclins that regulate the G1/S phase
      transition of the cell cycle. Expression of CCND3 is observed in nearly all
      proliferating cells; however, the presence of high levels of CCND3 has been
      linked to a poor prognosis for several types of cancer. Therefore, further
      mechanistic studies on the regulation of CCND3 expression are urgently needed to
      provide therapeutic implications. In this study, we report that a conserved RNA G
      quadruplex-forming sequence (hereafter CRQ), located in the 5' UTR of mammalian
      CCND3 mRNA, is able to fold into an extremely stable, intramolecular, parallel G
      quadruplex in vitro. The CRQ G-quadruplex dramatically reduces the activity of a
      reporter gene in human cell lines, but it has little impact on its mRNA level,
      indicating a translational repression. Moreover, the CRQ sequence in its natural
      context inhibits translation of CCND3. Disruption of the G-quadruplex structure
      by G/U-mutation or deletion results in an elevated expression of CCND3 and an
      increased phosphorylation of Rb, a downstream target of CCND3, which promotes
      progression of cells through the G1 phase. Our results add to the growing
      understanding of the regulation of CCND3 expression and provide a potential
      therapeutic target for cancer treatment.

PMID- 22858675
TI  - Targeting ribosome assembly on the HCV RNA using a small RNA molecule.
AB  - Translation initiation of hepatitis C Virus (HCV) RNA is the initial obligatory
      step of the viral life cycle, mediated through the Internal Ribosome Entry Site
      (IRES) present in the 5'-untranslated region (UTR). Initiation on the HCV IRES is
      mediated by multiple structure-specific interactions between IRES RNA and host
      40S ribosomal subunit. In the present study we demonstrate that the SLIIIef
      domain, in isolation from other structural elements of HCV IRES, retain the
      ability to interact with 40S ribosome subunit. A small RNA SLRef, mimicking the
      SLIIIef domain was found to interact specifically with human La protein and the
      ribosomal protein S5 and selectively inhibit HCV RNA translation. More
      importantly, SLRef RNA showed significant suppression of replication in HCV
      monocistronic replicon and decrease of negative strand synthesis in HCV cell
      culture system. Finally, using Sendai virus based virosome, the targeted delivery
      of SLRef RNA into mice liver succeeded in selectively inhibiting HCV IRES
      mediated translation in vivo.

PMID- 22858676
TI  - An effort to make sense of antisense transcription in bacteria.
AB  - Analysis of bacterial transcriptomes have shown the existence of a genome-wide
      process of overlapping transcription due to the presence of antisense RNAs, as
      well as mRNAs that overlapped in their entire length or in some portion of the 5'
      and 3'-UTR regions. The biological advantages of such overlapping transcription
      are unclear but may play important regulatory roles at the level of
      transcription, RNA stability and translation. In a recent report, the human
      pathogen Staphylococcus aureus is observed to generate genome-wide overlapping
      transcription in the same bacterial cells leading to a collection of short RNA
      fragments generated by the endoribonuclease III, RNase III. This processing
      appears most prominently in Gram-positive bacteria. The implications of both the
      use of pervasive overlapping transcription and the processing of these double
      stranded templates into short RNAs are explored and the consequences discussed.

PMID- 22858677
TI  - Role of Ser7 phosphorylation of the CTD during transcription of snRNA genes.
AB  - The largest subunit of RNA polymerase (pol) II, Rpb1, contains an unusual
      carboxyl-terminal domain (CTD) composed of consecutive repeats of the sequence
      Tyr-Ser-Pro-Thr-Ser-Pro-Ser (Y 1S 2P 3T 4S 5P 6S 7). During transcription, Ser2,
      Ser5 and Ser7 are subjected to dynamic phosphorylation and dephosphorylation by
      CTD kinases and phosphatases, creating a characteristic CTD phosphorylation
      pattern along genes. This CTD "code" allows the coupling of transcription with co
      transcriptional RNA processing, through the timely recruitment of the appropriate
      factors at the right point of the transcription cycle. In mammals,
      phosphorylation of Ser7 (Ser7P) is detected on all pol II-transcribed genes, but
      is only essential for expression of a sub-class of genes encoding small nuclear
      (sn)RNAs. The molecular mechanisms by which Ser7P influences expression of these
      particular genes are becoming clearer. Here, I discuss our recent findings
      clarifying how Ser7P facilitates transcription of these genes and 3'end
      processing of the transcripts, through recruitment of the RPAP2 phosphatase and
      the snRNA gene-specific Integrator complex.

PMID- 22858678
TI  - Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and
      development.
AB  - The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non
      coding RNA (lncRNA) that has been discovered as a marker for lung cancer
      metastasis. It is highly abundant, its expression is strongly regulated in many
      tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well
      as physiological processes, and it is associated with many RNA binding proteins
      and highly conserved throughout evolution. The nuclear transcript MALAT-1 has
      been functionally associated with gene regulation and alternative splicing and
      its regulation has been shown to impact proliferation, apoptosis, migration and
      invasion. Here, we have developed a human and a mouse knockout system to study
      the loss-of-function phenotypes of this important ncRNA. In human tumor cells,
      MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the
      quantitative loss of MALAT1 did neither affect proliferation nor cell cycle
      progression nor nuclear architecture in human lung or liver cancer cells.
      Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to
      any obvious phenotype or histological abnormalities in Malat1-null compared with
      wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is
      compatible with cell viability and normal development.

PMID- 22858679
TI  - Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma.
AB  - Studies of miRNA association with Argonaute (AGO) proteins in mammalian cells
      have indicated lack of bias toward particular AGO. However, to our knowledge, the
      use of quantitative methods for studying miRNA association with different AGOs
      has not been reported so far. In this work we compared the total miRNA content in
      AGO1 and AGO2 immunoprecipitates obtained from MCF7 adenocarcinoma cells using
      TaqMan Low Density miRNA Arrays and successfully verified selected miRNAs with
      qPCR. For most of the miRNA species AGO1 and AGO2 profiles were well correlated,
      however, some miRNAs demonstrated consistent biases toward one of the Argonautes.
      Furthermore, miRNAs which were predominantly AGO2-associated derived mostly from
      sense strands of the corresponding pre-miRNAs while the majority of AGO1 biased
      miRNAs originated from antisense strands of the pre-miRNAs. Additionally, we show
      that circulating miRNA in human blood plasma can be immunoprecipitated with both
      AGO1 and AGO2 antibody. However, unlike in cell lysates, AGO1 and AGO2 associated
      miRNA profiles in plasma did not correlate, indicating that many cell types
      contribute to circulating miRNA (given that expression of AGO proteins is tissue
      specific). Furthermore, AGO-specific miRNA profiles in blood cells differed
      significantly from miRNAs profiles in plasma indicating that most circulating
      miRNAs are likely to derive from non-blood cells. Since circulating miRNAs hold
      great promise as biomarkers for numerous cancers and other diseases, we
      hypothesize that AGO-specific miRNA profiles might add an additional dimension to
      circulating miRNA-based diagnostics.

PMID- 22858680
TI  - Spatio-temporal regulation of ADAR editing during development in porcine neural
      tissues.
AB  - Editing by ADAR enzymes is essential for mammalian life. Still, knowledge of the
      spatio-temporal editing patterns in mammals is limited. By use of 454 amplicon
      sequencing we examined the editing status of 12 regionally extracted mRNAs from
      porcine developing brain encompassing a total of 64 putative ADAR editing sites.
      In total 24 brain tissues, dissected from up to five regions from embryonic
      gestation day 23, 42, 60, 80, 100 and 115, were examined for editing. Generally,
      editing increased during embryonic development concomitantly with an increase in
      ADAR2 mRNA level. Notably, the Gria2 (GluR-B) Q/R site, reported to be ~100%
      edited in previous studies, is only 54% edited at embryonic day 23. Transcripts
      with multiple editing sites in close proximity to each other exhibit coupled
      editing and an extraordinary incidence of long-range coupling of editing events
      more than 32 kb apart is observed for the kainate glutamate receptor 2
      transcript, Grik2. Our study reveals complex spatio-temporal ADAR editing
      patterns of coordinated editing events that may play important roles in the
      development of the mammalian brain.

PMID- 22858681
TI  - Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical
      mouse models of early and advanced gastrointestinal neoplasia.
AB  - The Aurora family of kinases, play a fundamental role in cell division and are
      overexpressed in several cancers including colon. The activity of barasertib
      hQPA, a selective inhibitor of Aurora-B kinase (ABK) was investigated in a range
      of preclinical models of gastrointestinal cancer. Treatment with barasertib-hQPA
      produced anti-proliferative and cytotoxic effects across a panel of human
      colorectal cancer (CRC) cell lines in vitro. Prodrug, barasertib [48-h
      subcutaneous (s.c.) infusion; 150 mg/kg/day] inhibited the growth of SW620,
      Colo205, HCT116 human colorectal tumor xenografts in nude mice significantly
      (Student's t-test, P<0.05, n=10-12 per group). Flow cytometric analysis of single
      cells from disaggregated barasertib-treated SW620 tumors revealed a decrease in
      phosphorylated histone H3 (phH3) and an increase in tumor cells with >=4N DNA
      content P<0.05). The activity of barasertib was then examined in ApcMin/+ mice, a
      spontaneous model of early intestinal neoplasia. Macroscopic evaluation of the
      small intestine revealed that barasertib treatment [25 mg/kg intra-peritoneal
      (i.p.) Q1Dx4 each week for 3 weeks] of 8-week old ApcMin/+ mice produced a 39%
      reduction in macroadenoma number (P=0.02) and a 43% reduction in overall adenoma
      burden (P=0.02) compared with vehicle-treated controls. Quantification of
      microscopic adenomas revealed a >64% reduction in the number of adenomas spanning
      more than one villus. Histological analysis of these adenomas revealed a number
      of distinct changes in barasertib-treated ApcMin/+ mice, including a 94%
      reduction in the proportion of phospho-histone H3-positive cells (P<0.001) and a
      53% reduction in the number of cells per adenoma (P=0.001). These results provide
      a scientific rationale for investigating ABK inhibitors as a treatment for
      intestinal cancer.

PMID- 22858682
TI  - Intra-arterial intraoperative computed tomography angiography guided navigation: 
      a new technique for localization of vascular pathology.
AB  - BACKGROUND: Precise intraoperative surgical localization of small distal
      aneurysms, arteriovenous malformations (AVMs), and cranial base dural
      arteriovenous fistulae may be challenging. Current neuronavigational techniques
      are based on imaging techniques with limited sensitivity to detect vascular
      lesions that are small. We introduce the technique of intraoperative computed
      tomography angiography (iCTA) with an intra-arterial injection for surgical
      navigation. OBJECTIVE: To determine whether iCTA integrated with a navigation
      platform is accurate and useful for precise localization of small vascular
      lesions that are challenging to treat. METHODS: This study included 8 patients: 2
      with aneurysms, 3 with small cortical AVMs, and 3 with cranial base dural
      arteriovenous fistulae. iCTA with intra-arterial contrast injection was performed
      in all patients for precise localization of the small vascular lesion to
      facilitate craniotomy planning and microsurgical approach. All operative reports,
      inpatient and outpatient records, and radiographic studies available were
      reviewed retrospectively. RESULTS: : The iCTA was used to target 2 aneurysms, 3
      small subcortical AVMs, and 3 dural arteriovenous fistulae. This technique was
      most helpful to localize the 3 AVMs and the distal M4 aneurysm precisely.
      Craniotomy planning was accurate in all instances; no complications related to
      the technique were noted, and all patients had uneventful postoperative
      recoveries. CONCLUSION: iCTA is an effective and accurate novel technique that
      can enhance the safety of surgical treatment for small intra-axial vascular
      pathology. ABBREVIATIONS: AVM, arteriovenous malformationCTA, computed tomography
      angiographyDAVF, dural arteriovenous fistulaDSA, digital subtraction
      angiographyiCTA, intraoperative computed tomography angiographyMCA, middle
      cerebral arteryMSCT, multislice computed tomographyMRA, magnetic resonance
      angiography.

PMID- 22858683
TI  - A very simple method to synthesize nano-sized manganese oxide: an efficient
      catalyst for water oxidation and epoxidation of olefins.
AB  - Nano-sized particles of manganese oxides have been prepared by a very simple and
      cheap process using a decomposing aqueous solution of manganese nitrate at 100 
      degrees C. Scanning electron microscopy, transmission electron microscopy and X
      ray diffraction spectrometry have been used to characterize the phase and the
      morphology of the manganese oxide. The nano-sized manganese oxide shows efficient
      catalytic activity toward water oxidation and the epoxidation of olefins in the
      presence of cerium(IV) ammonium nitrate and hydrogen peroxide, respectively.

PMID- 22858685
TI  - Evaluation of the promoter polymorphism -911C>A in the 3-hydroxy-3-methylglutaryl
      Coenzyme A reductase gene with coronary artery disease risk and cholesterol
      levels in a population from Western India.

PMID- 22858686
TI  - Interview with Gautam Desiraju.

PMID- 22858684
TI  - Automaticity in anxiety disorders and major depressive disorder.
AB  - In this paper we examine the nature of automatic cognitive processing in anxiety
      disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity
      as a unitary construct, we follow a social cognition perspective (Bargh, 1994)
      that argues for four theoretically independent features of automaticity:
      unconscious (processing of emotional stimuli occurs outside awareness), efficient
      (processing emotional meaning uses minimal attentional resources), unintentional
      (no goal is needed to engage in processing emotional meaning), and uncontrollable
      (limited ability to avoid, alter or terminate processing emotional stimuli). Our
      review of the literature suggests that most anxiety disorders are characterized
      by uncontrollable, and likely also unconscious and unintentional, biased
      processing of threat-relevant information. In contrast, MDD is most clearly
      typified by uncontrollable, but not unconscious or unintentional, processing of
      negative information. For the anxiety disorders and for MDD, there is no
      sufficient evidence to draw firm conclusions about efficiency of processing,
      though early indications are that neither anxiety disorders nor MDD are
      characterized by this feature. Clinical and theoretical implications of these
      findings are discussed and directions for future research are offered. In
      particular, it is clear that paradigms that more directly delineate the different
      features of automaticity are required to gain a more comprehensive and systematic
      understanding of the importance of automatic processing in emotion dysregulation.

PMID- 22858687
TI  - Tuning the plasmon resonance of a nano-mouth array.
AB  - We have developed a method to fabricate a silver nano-mouth array via a cost
      effective inverted hemispherical colloidal lithography method. It shows that the
      nano-mouth supports a strong localized surface plasmon resonance, which results
      in an extraordinary optical transmission peak. When the nano-mouth array is
      transferred onto a polydimethylsiloxane (PDMS) substrate, we show that the
      localized surface plasmon resonance can be tuned via the swelling and recovery of
      the PDMS in ethyl acetate solvent. The resonant peak can be tuned with a relative
      bandwidth of over 10%. We also demonstrate the refractive index sensitivity of
      the nano-mouth array at a wavelength of 1300 nm. This structure might be useful
      for optical microfluidic devices and sensors.

PMID- 22858689
TI  - Functional morphology and evolution of specialized mouthparts of Cephenniini
      (Insecta, Coleoptera, Staphylinidae, Scydmaeninae).
AB  - We present the results of a morphological study of the labium and labial
      (premental) discs in Cephenniini, ant-like stone beetles feeding on oribatid
      mites. The discs are composed of a cuticular plate connected by a circumferential
      ring with the hypopharyngeal suspensorium. The discs have likely developed from
      the premental cuticle and from internal sclerotizations of the labium. The shape
      of the external plate can be changed from flat to concave and vice versa by
      contractions and relaxations of the labial muscles. Contractions result in a flat
      or only slightly concave shape whereas during relaxation the discs become
      strongly concave and adhere tightly to the captured mite. Once this is achieved,
      detaining of the prey is energy-free. Based on known hypotheses concerning the
      evolution of Oribatida and Staphylinidae, we exclude the possibility of a co
      evolution of "proto-Cephenniini" with yet unarmored "proto-Oribatida", and
      suggest three alternative scenarios: i) the predators co-evolved with a
      particular early lineage of Oribatida that has acquired the hard armor relatively
      recently; ii) ancestors of Cephenniini gradually shifted from feeding on other
      types of prey towards fully armored Oribatida; or iii) the labial discs have
      originally developed for functions not related to feeding.

PMID- 22858690
TI  - Electrochemical behavior of o-sec-butylphenol at glassy carbon electrode modified
      with multiwalled carbon nanotubes and 1-butyl-3-methylimidazolium
      hexafluorophosphate.
AB  - A sensitive electrochemical sensor based on immobilized multiwalled carbon
      nanotubes (MWCNTs) and 1-butyl-3-methylimidazolium hexafluorophosphate
      (BMIM.PF(6)) on a glassy carbon electrode (GCE) for o-sec-butylphenol (osBP) was
      proposed. The electro-oxidation behavior was studied, the experimental conditions
      were optimized and kinetic parameters were calculated. The results indicated that
      this electrochemical sensor has the advantages of fast electron-transfer rate,
      minimal fouling of electrodes, high sensitivity and stability for o-sec
      butylphenol. Upon comparison with a glassy carbon electrode, this senor would
      effectively minimize the over-potential and increase the electrochemical response
      to o-sec-butylphenol. Under the optimum conditions, the peak current was linear
      to the osBP concentration range from 1 * 10(-7) to 2.5 * 10(-5) M with the
      detection limit of 8.65 * 10(-9) M (S/N = 3). The proposed method was applied to
      the determination of spiked water samples with satisfactory results.

PMID- 22858688
TI  - Toward personalized cancer nanomedicine - past, present, and future.
AB  - Tumors are composed of highly proliferate, migratory, invasive, and therapy
      evading cells. These characteristics are conferred by an enormously complex
      landscape of genomic, (epi-)genetic, and proteomic aberrations. Recent efforts to
      comprehensively catalogue these reversible and irreversible modifications have
      began to identify molecular mechanisms that contribute to cancer pathophysiology,
      serve as novel therapeutic targets, and may constitute biomarkers for early
      diagnosis and prediction of therapy responses. With constantly evolving
      technologies that will ultimately enable a complete survey of cancer genomes, the
      challenges for discovery cancer science and drug development are daunting.
      Bioinformatic and functional studies must differentiate cancer-driving and 
      contributing mutations from mere bystanders or 'noise', and have to delineate
      their molecular mechanisms of action as a function of collaborating oncogenic and
      tumor suppressive signatures. In addition, the translation of these genomic
      discoveries into meaningful clinical endpoints requires the development of co
      extinction strategies to therapeutically target multiple cancer genes, to
      robustly deliver therapeutics to tumor sites, and to enable widespread
      dissemination of therapies within tumor tissue. In this perspective, I will
      describe the most current paradigms to study and validate cancer gene function. I
      will highlight advances in the area of nanotechnology, in particular, the
      development of RNA interference (RNAi)-based platforms to more effectively
      deliver therapeutic agents to tumor sites, and to modulate critical cancer genes
      that are difficult to target using conventional small-molecule- or antibody-based
      approaches. I will conclude with an outlook on the deluge of challenges that
      genomic and bioengineering sciences must overcome to make the long-awaited era of
      personalized nano-medicine a clinical reality for cancer patients.

PMID- 22858692
TI  - Effects of dimethylolpropionic acid modification on the characteristics of
      polyethylene terephthalate fibers.
AB  - Polyethylene terephthalate (PET) fibers are widely used in the preparation of
      artificial ligaments. However, due to their lack of hydrophilicity, PET fibers
      have low biocompatibility, which usually results in the poor biological activity
      of the products. In the present study, in order to improve the hydrophilicity and
      biocompatibility of PET fibers, we modified their surface using
      dimethylolpropionic acid (DMPA). Scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC),
      X-ray diffraction (XRD), tensile testing and cell culture were employed to
      observe the effects of DMPA modification on the characteristics of the DMPA-PET
      fibers. In contrast to the original PET fibers, the surface of the DMPA-PET
      fibers became rough as demonstrated by SEM. The FTIR spectrum further confirmed
      that a number of hydrophilic groups were formed on the surface of DMPA-PET.
      However, there were no significant changes in crystallinity and tensile strength
      between the PET and the DMPA-PET fibers as revealed by DSC and XRD (P>0.05).
      Finally, the cell co-culture test revealed that the adhesion and proliferation of
      bone marrow-derived stromal cells increased greatly on the DMPA-PET fibers
      compared to those on the original PET fibers (P<0.05). These results demonstrate
      that DMPA-PET fibers have significant potential as a material for the development
      of artificial ligaments.

PMID- 22858691
TI  - Structure analysis between the SWAP-70 RHO-GEF and the newly described PLD2-GEF.
AB  - Small GTPases like Rac2 are crucial regulators of many cell functions central to
      life itself. Our laboratory has recently found that phospholipase D2 (PLD2) can
      act as a guanine nucleotide exchange factor (GEF) for Rac2. PLD2 has a Pleckstrin
      Homology (PH) domain but does not bear a Dbl homology (DH) or DOCK homology
      region (DHR) domain. It has, however, a Phox (PX) domain upstream of its PH
      domain. To better understand the novel finding of PLD2 as an enhancer of GDP/GTP
      exchange, we modeled the N-terminal portion of PLD2 (as the crystal structure of
      this protein has not as of yet been resolved), and studied the correlation with
      two known GEFs, SWAP-70 and the Leukemic Associated RhoGEF (LARG). Structural
      similarities between PLD2's PH and SWAP-70s or LARG's PH domain are very
      extensive, while similarities between PLD2's PX and SWAP-70s or LARG's DH domains
      are less evident. This indicates that PLD functions as a GEF utilizing its PH
      domain and part of its PX domain and possibly other regions. All this makes PLD
      unique, and an entirely new class of GEF. By bearing two enzymatic activities
      (break down of PC and GDP/GTP exchange), it is realistic to assume that PLD is an
      important signaling node for several intracellular pathways. Future experiments
      will ascertain how the newly described PLD2's GEF is regulated in the context of
      cell activation.

PMID- 22858693
TI  - Unusually high-performing organic field-effect transistors based on pi-extended
      semiconducting porphyrins.
AB  - Highly conjugated porphyrin derivatives, H(2) TP and ZnTP, are synthesized. J
      aggregations of the H-aggregated dimeric porphyrin pairs are clearly observed by
      their single crystal structures that facilitate slip-stacked charge transport
      phenomenon. In particular, their SC-FETs show the highest field-effect mobilities
      of 0.85-2.90 cm(2)  V(-1) s(-1) . Furthermore, the ZnTP-based OPT displays a
      dramatic photoinduced current enhancement with a high photoresponsivity of 22 000
      A W(-1)  under a very low light intensity (5.6 m W cm(-2) ).

PMID- 22858696
TI  - Prevalence of enamel defects and associated risk factors in both dentitions in
      preterm and full term born children.
AB  - OBJECTIVES: The aim of this study was to evaluate the prevalence of enamel
      defects and their risk factors on primary and permanent dentitions of prematurely
      born children and full-term born children born at Regional Hospital of Asa Sul,
      Brasilia, DF, Brazil. MATERIAL AND METHODS: Eighty 5-10-year-old children of both
      genders were examined, being 40 born prematurely (G1) and 40 born full term (G2).
      The demographic variables, medical history and oral health behaviors were
      retrieved using a questionnaire and data obtained from clinical examination were
      recorded. The teeth were examined and the presence of enamel defects was
      diagnosed according to the DDE Index and registered in odontograms. Subsequently,
      the defects were categorized in four groups according to one of the criteria
      proposed in 1992 by the FDI Commission on Oral Health, Research and Epidemiology.
      Kruskal-Wallis, Chi-square, Kappa, Mann-Whitney tests and logistic regression
      were used for statistical analysis. RESULTS: 75% of total sample had enamel
      defects. There was a major prevalence of hypoplasia of the enamel in G1
      (p<0.001). There was a significant relationship between low weight and presence
      of the imperfections on the enamel in G1 on the primary dentition. The logistic
      regression model showed that the other risk factors such as monthly per capita
      family income, educational level, dietary and hygiene habits, fluoride exposure,
      trauma, and diseases were not associated with enamel defects and caries.
      CONCLUSIONS: Pre-term labor can be a predisposing factor for the presence of the
      enamel hypoplasia in the primary dentition.

PMID- 22858697
TI  - Iron supplementation reduces the erosive potential of a cola drink on enamel and
      dentin in situ.
AB  - Iron has been suggested to reduce the erosive potential of cola drinks in vitro.
      OBJECTIVE: The aim of this study was to evaluate in situ the effect of ferrous
      sulfate supplementation on the inhibition of the erosion caused by a cola drink.
      MATERIAL AND METHODS: Ten adult volunteers participated in a crossover protocol
      conducted in two phases of 5 days, separated by a washout period of 7 days. In
      each phase, they wore palatal devices containing two human enamel and two human
      dentin blocks. The volunteers immersed the devices for 5 min in 150 mL of cola
      drink (Coca-ColaTM, pH 2.6), containing ferrous sulfate (10 mmol/L) or not
      (control), 4 times per day. The effect of ferrous sulfate on the inhibition of
      erosion was evaluated by profilometry (wear). Data were analyzed by paired t
      tests (p<0.05). RESULTS: The mean wear (+/-se) was significantly reduced in the
      presence of ferrous sulfate, both for enamel (control: 5.8+/-1.0 um; ferrous
      sulfate: 2.8+/-0.6 um) and dentin (control: 4.8+/-0.8 um; ferrous sulfate: 1.7+/
      0.7 um). CONCLUSIONS: The supplementation of cola drinks with ferrous sulfate can
      be a good alternative for the reduction of their erosive potential. Additional
      studies should be done to test if lower ferrous sulfate concentrations can also
      have a protective effect as well as the combination of ferrous sulfate with other
      ions.

PMID- 22858695
TI  - Mechanisms of action of systemic antibiotics used in periodontal treatment and
      mechanisms of bacterial resistance to these drugs.
AB  - Antibiotics are important adjuncts in the treatment of infectious diseases,
      including periodontitis. The most severe criticisms to the indiscriminate use of
      these drugs are their side effects and, especially, the development of bacterial
      resistance. The knowledge of the biological mechanisms involved with the
      antibiotic usage would help the medical and dental communities to overcome these
      two problems. Therefore, the aim of this manuscript was to review the mechanisms
      of action of the antibiotics most commonly used in the periodontal treatment
      (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main
      mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can
      be classified into three groups: intrinsic, mutational and acquired. Penicillin,
      tetracycline and erythromycin are broad-spectrum drugs, effective against gram
      positive and gram-negative microorganisms. Bacterial resistance to penicillin may
      occur due to diminished permeability of the bacterial cell to the antibiotic;
      alteration of the penicillin-binding proteins, or production of beta-lactamases.
      However, a very small proportion of the subgingival microbiota is resistant to
      penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting
      their access to the cell, by altering the ribosome in order to prevent effective
      binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes.
      Periodontal pathogens may become resistant to these drugs. Finally, metronidazole
      can be considered a prodrug in the sense that it requires metabolic activation by
      strict anaerobe microorganisms. Acquired resistance to this drug has rarely been
      reported. Due to these low rates of resistance and to its high activity against
      the gram-negative anaerobic bacterial species, metronidazole is a promising drug
      for treating periodontal infections.

PMID- 22858698
TI  - 56-month clinical performance of Class I and II resin composite restorations.
AB  - OBJECTIVE: This study evaluated the 56-month clinical performance of Class I and
      II resin composite restorations. Filtek P60 was compared with Filtek Z250, which
      are both indicated for posterior restorations but differ in terms of handling
      characteristics. The null hypothesis tested was that there is no difference in
      the clinical performance of the two resin composites in posterior teeth. MATERIAL
      AND METHODS: Thirty-three patients were treated by the same operator, who
      prepared 48 Class I and 42 Class II cavities, which were restored with Single
      Bond/Filtek Z250 or Single Bond/Filtek P60 restorative systems. Restorations were
      evaluated by two independent examiners at baseline and after 56 months, using the
      modified USPHS criteria. Data were analyzed statistically using Chi-square and
      Fisher's Exact tests (a=0.05). RESULTS: After 56 months, 25 patients (31 Class I
      and 36 Class II) were analyzed. A 3% failure rate occurred due to secondary
      caries and excessive loss of anatomic form for P60. For both restorative systems,
      there were no significant differences in secondary caries and postoperative
      sensitivity. However, significant changes were observed with respect to anatomic
      form, marginal discoloration, and marginal adaptation. Significant decreases in
      surface texture were observed exclusively for the Z250 restorations. CONCLUSIONS:
      Both restorative systems can be used for posterior restorations and can be
      expected to perform well in the oral environment.

PMID- 22858699
TI  - Qualitative SEM/EDS analysis of microleakage and apical gap formation of adhesive
      root-filling materials.
AB  - OBJECTIVE: The aim of this study was to compare the correspondence between gap
      formation and apical microleakage in root canals filled with epoxy resin-based
      (AH Plus) combined or not with resinous primer or with a dimethacrylate-based
      root canal sealer (Epiphany). MATERIAL AND METHODS: Thirty-nine lower single
      rooted human premolars were filled by the lateral condensation technique (LC) and
      immersed in a 50-wt% aqueous silver nitrate solution at 37oC (24 h). After
      longitudinal sectioning, epoxy resin replicas were made from the tooth specimens.
      Both the replicas and the specimens were prepared for scanning electron
      microscopy (SEM). The gaps were observed in the replicas. Apical microleakage was
      detected in the specimens by SEM/energy dispersive spectroscopy (SEM/EDS). The
      data were analyzed statistically using an Ordinal Logistic Regression model and
      Analysis of Correspondence (alpha=0.05). RESULTS: Epiphany presented more regions
      containing gaps between dentin and sealer (p<0.05). There was correspondence
      between the presence of gaps and microleakage (p<0.05). Microleakage was similar
      among the root-filling materials (p>0.05). CONCLUSIONS: The resinous primer did
      not improve the sealing ability of AH Plus sealer and the presence of gaps had an
      effect on apical microleakage for all materials.

PMID- 22858700
TI  - Ion release from a composite resin after exposure to different 10% carbamide
      peroxide bleaching agents.
AB  - OBJECTIVE: This in vitro study evaluated the influence of two 10% carbamide
      peroxide bleaching agents - a commercial product (Opalescence PF; Ultradent
      Products, Inc.) and a bleaching agent prepared in a compounding pharmacy - on the
      chemical degradation of a light-activated composite resin by determining its
      release of ions before and after exposure to the agents. MATERIAL AND METHODS:
      Thirty composite resin (Filtek Z250; 3M/ESPE) samples were divided into three
      groups: group I (exposed to Opalescence PF commercial bleaching agent), group II
      (exposed to a compounded bleaching agent) and group III (control - Milli-Q
      water). After 14 days of exposure, with a protocol of 8 h of daily exposure to
      the bleaching agents and 16 h of immersion in Milli-Q water, the analysis of ion
      release was carried out using a HP 8453 spectrophotometer. The values were
      analyzed statistically by ANOVA, Tukey's test and the paired t-tests. The
      significance level was set at 5%. RESULTS: After 14 days of the experiment,
      statistically significant difference was found between group II and groups I and
      III, with greater ion release from the composite resin in group II. CONCLUSIONS:
      The compounded bleaching agent had a more aggressive effect on the composite
      resin after 14 days of exposure than the commercial product and the control (no
      bleaching).

PMID- 22858701
TI  - Effects of a Mikania laevigata extract on bone resorption and RANKL expression
      during experimental periodontitis in rats.
AB  - OBJECTIVES: The Mikania laevigata extract (MLE) (popularly known in Brazil as
      "guaco") possesses anti-inflammatory properties. In the present study we tested
      the effects of MLE in a periodontitis experimental model in rats. We also
      investigated possible mechanisms underlying such effects. MATERIAL AND METHODS:
      Periodontal disease was induced by a ligature placed around the mandibular first
      molars of each animal. Male Wistar rats were divided into 4 groups: non-ligated
      animals treated with vehicle; non-ligated animals treated with MLE (10 mg/kg,
      daily); ligature-induced animals treated with vehicle and ligature-induced
      animals treated with MLE (10 mg/kg, daily). Thirty days after the induction of
      periodontal disease, the animals were euthanized and mandibles and gingival
      tissues removed for further analysis. RESULTS: Morphometric analysis of alveolar
      bone loss demonstrated that MLE-treated animals presented a decreased alveolar
      bone loss and a lower expression of the activator of nuclear factor-kappaB ligand
      (RANKL) measured by immunohistochemistry. Moreover, gingival tissues from the MLE
      treated group showed decreased neutrophil migration myeloperoxidase (MPO) assay.
      CONCLUSIONS: These results indicate that MLE may be useful to control bone
      resorption during progression of experimental periodontitis in rats.

PMID- 22858702
TI  - Sealability of MTA and calcium hydroxidecontaining sealers.
AB  - OBJECTIVES: The aim of this study was to evaluate the apical sealability of
      Fillapex(r), endo-CPM-Sealer(r) and Sealapex(r). MATERIAL AND METHODS: Ninety
      four freshly extracted single-rooted teeth were selected and decoronated. All
      teeth were radiographed to confirm the existence of a single and straight root
      canal, which was prepared using Protaper Universal and 2.5% sodium hypochlorite.
      The teeth were randomly divided in groups of 10 specimens each according to the
      sealer, and the canals were filled using the single cone technique and one of the
      sealers. Four additional teeth were used as controls. The teeth were submitted to
      dye leakage with Rhodamine B for 24 h but using vacuum on the initial 15 min.
      Thereafter, they were cut longitudinally and the leakage was measured in a linear
      fashion from apex to crown. Data were analyzed by ANOVA and Tukey's tests at 5%
      significance level. RESULTS: Fillapex(r) and Sealapex(r) showed significantly
      less dye leakage than endo-CPM-Sealer(r) (p<0.05). CONCLUSIONS: It was concluded
      that Fillapex(r) and Sealapex(r) were able to prevent apical dye leakage
      differently from endo-CPM-Sealer(r).

PMID- 22858703
TI  - A 12-month clinical evaluation of pit-and-fissure sealants placed with and
      without etch-and-rinse and self-etch adhesive systems in newly-erupted teeth.
AB  - OBJECTIVES: The objective of this one-year clinical study was to investigate the
      effect of two adhesive systems (Adper Single Bond, a two-step etch-and-rinse and
      Clearfil SE Bond, a two-step self-etch system) on pit-and-fissure sealant
      retention in newly-erupted teeth. This study compared the success of the sealants
      in mesial and distopalatal grooves with and without these two adhesive systems.
      MATERIAL AND METHODS: In a clinical trial, 35 children aged 6-8 years undergoing
      sealant placement were recruited. This one-year clinical study scored 70 mesial
      and 70 distopalatal sealants of newly-erupted permanent maxillary first molar,
      with a split-mouth design. All children received sealant alone in one permanent
      maxillary molar tooth. Children were randomized into two groups. One group
      received Self-etch (Se) bond plus sealant and the other group received Single
      Bond plus sealant in another permanent maxillary molar tooth. Clinical evaluation
      at 3, 6 and 12 months was performed and the retention was studied in terms of the
      success and failure. RESULTS: The success rate of sealant in the distopalatal
      groove, using SeB at 3, 6 and 12 months was 93.3% (95% CI: 68.0, 99.8), 73.3%
      (95% CI: 44.9, 92.2) and 66.7% (95% CI: 38.4, 88.2), respectively. It was greater
      than that of the distopalatal groove in SB group with a success rate of 62.5%
      (95% CI: 35.4, 84.8), 31.3% (95% CI: 11.8, 58.7) and 31.3% (95% CI: 11.8, 58.7),
      at the three evaluation periods. The success rate of sealant in the mesial groove
      using SeB was 86.6% (95% CI: 59.5, 98.3), 53.3% (95% CI: 26.6, 78.7) and 53.3%
      (95% CI: 26.6, 78.7), while this was 100% (95% CI: 79.4, 100.0), 81.3% (95% CI:
      54.4, 96.0) and 81.3% (95% CI: 54.4, 96.0) using SB, at 3, 6 and 12-month
      evaluation periods. CONCLUSIONS: These results support the use of these two
      bonding agents in pit-and-fissure sealants under both isolated and contaminated
      conditions. Further, Se bond seemed to be less sensitive to moisture
      contamination.

PMID- 22858704
TI  - Influence of lingual bracket position on microbial and periodontal parameters in
      vivo.
AB  - OBJECTIVE: Lingual orthodontics is becoming more popular in dental practice. The
      purpose of the present investigation was to compare plaque formation on teeth
      bonded with the same bracket onto buccal or lingual surface, with non-bonded
      control teeth, via an in vivo growth experiment over a 30-day period. MATERIAL
      AND METHODS: A randomized controlled trial with split-mouth design was set up
      enrolling 20 dental students. Within each subject sites with buccal and lingual
      brackets and control sites were followed. Clinical periodontal parameters
      (periodontal pocket depth: PPD; bleeding on probing: BOP) were recorded at
      baseline and on days 1, 7 and 30. Microbiological samples were taken from the
      brackets and the teeth on days 1, 7 and 30 to detect colony-forming units (CFU).
      Total CFU, streptococci CFU and anaerobe CFU were measured. RESULTS: No
      significant differences (P>0.05) were found between buccal and lingual brackets
      in terms of clinical periodontal parameters and microbiological values.
      CONCLUSION: Bracket position does not have significant impact on bacterial load
      and on periodontal parameters.

PMID- 22858705
TI  - Periodontal ligament influence on the stress distribution in a removable partial
      denture supported by implant: a finite element analysis.
AB  - OBJECTIVES: The non-homogenous aspect of periodontal ligament (PDL) has been
      examined using finite element analysis (FEA) to better simulate PDL behavior. The
      aim of this study was to assess, by 2-D FEA, the influence of non-homogenous PDL
      on the stress distribution when the free-end saddle removable partial denture
      (RPD) is partially supported by an osseointegrated implant. MATERIAL AND METHODS:
      Six finite element (FE) models of a partially edentulous mandible were created to
      represent two types of PDL (non-homogenous and homogenous) and two types of RPD
      (conventional RPD, supported by tooth and fibromucosa; and modified RPD,
      supported by tooth and implant [10.00x3.75 mm]). Two additional Fe models without
      RPD were used as control models. The non-homogenous PDL was modeled using beam
      elements to simulate the crest, horizontal, oblique and apical fibers. The load
      (50 N) was applied in each cusp simultaneously. Regarding boundary conditions the
      border of alveolar ridge was fixed along the x axis. The FE software (Ansys 10.0)
      was used to compute the stress fields, and the von Mises stress criterion (svM)
      was applied to analyze the results. RESULTS: The peak of svM in non-homogenous
      PDL was higher than that for the homogenous condition. The benefits of implants
      were enhanced for the non-homogenous PDL condition, with drastic svM reduction on
      the posterior half of the alveolar ridge. The implant did not reduce the stress
      on the support tooth for both PDL conditions. CONCLUSION: The PDL modeled in the
      non-homogeneous form increased the benefits of the osseointegrated implant in
      comparison with the homogeneous condition. Using the non-homogenous PDL, the
      presence of osseointegrated implant did not reduce the stress on the supporting
      tooth.

PMID- 22858706
TI  - Expression of the cell cycle regulation proteins p53 and p21WAF1 in different
      types of non-dysplastic leukoplakias.
AB  - OBJECTIVES: The aim of this study was to analyze the immunolabeling of two cell
      cycle protein regulators, p53 and p21WAF1, in non-dysplastic leukoplakias with
      different epithelial alterations: acanthosis, hyperkeratosis and acanthosis
      combined with hyperkeratosis, and compare them with dysplastic leukoplakias.
      MATERIAL AND METHODS: This was a prospective cohort study involving 36 patients
      with oral homogeneous leukoplakias. excisional biopsies were performed and the
      patients remain under clinical follow-up. The leukoplakias were divided into four
      groups: 6 acanthosis, 9 hyperkeratosis, 10 acanthosis combined with
      hyperkeratosis, and 11 epithelial dysplasias. Paraffin-embebeded sections were
      immunostained for p53 and p21WAF1. Five hundred cells from the basal layer and
      500 from the parabasal layer were counted to determine the percentage of positive
      cells. A qualitative analysis was also carried out to determine the presence or
      absence of immunohistochemical staining in the intermediate and superficial
      layers. Groups were compared with ANOVA (p<0.05). Pearson's correlation
      coefficient was used to test for associations between the two markers, p53 and
      p21WAF1. RESULTS: No leukoplakia recurred and no malignant transformation was
      observed whitin a follow-up period of 3-6 years. The mean percentage of p53
      staining in the basal and parabasal layers was similar in all groups. p21WAF1
      staining differed between layers was as follows: in the basal, only 3 to 4% of
      cells were stained, while in the parabasal, between 16 and 28% of the epithelial
      cells were stained in the four different studied groups with no statistically
      significant difference (p>0.05). CONCLUSIONS: Our findings failed to
      differentiate the non-dysplastic lesions by means of p53 and p21WAF1
      immunostaining, notwithstanding similar profiles between non-dysplastic and
      dysplastic leukoplakias were observed.

PMID- 22858707
TI  - Influence of concentration, time and method of application of citric acid and
      sodium citrate in root conditioning.
AB  - OBJECTIVES: The aim of this study was to establish the parameters of
      concentration, time and mode of application of citric acid and sodium citrate in
      relation to root conditioning. MATERIAL AND METHODS: A total of 495 samples were
      obtained and equally distributed among 11 groups (5 for testing different
      concentrations of citric acid, 5 for testing different concentrations of sodium
      citrate and 1 control group). After laboratorial processing, the samples were
      analyzed under scanning electron microscopy. A previously calibrated and blind
      examiner evaluated micrographs of the samples. Non-parametric statistical
      analysis was performed to analyze the data obtained. RESULTS: Brushing 25% citric
      acid for 3 min, promoted greater exposure of collagen fibers in comparison with
      the brushing of 1% citric acid for 1 minute and its topical application at 1% for
      3 min. Sodium citrate exposed collagen fibers in a few number of samples.
      CONCLUSION: Despite the lack of statistical significance, better results for
      collagen exposure were obtained with brushing application of 25% citric acid for
      3 min than with other application parameter. Sodium citrate produced a few number
      of samples with collagen exposure, so it is not indicated for root conditioning.

PMID- 22858708
TI  - Wear of double crown systems: electroplated vs. casted female part.
AB  - OBJECTIVES: The wear of telescopic crowns is a common problem often reducing the
      patient's satisfaction with the denture and resulting in a renewal of the
      denture. The study aims to compare the wear behavior of conical crowns using
      electroplated copings (group E ) with standard telescopic crowns with cast female
      parts (group C). MATERIAL AND METHODS: 10 conical crowns were milled for each
      group of a cast gold alloy. The specimen of group E had a conicity of 2o. The
      cast secondary crowns of group C had a 0o design. The electroplated coping was
      established by direct electroforming. An apparatus accomplishing 10,000 wear
      cycles performed the wear test. The retentive forces and the correlating distance
      during insertion and separation were measured. The wear test was separated in a
      start phase, an initial wear phase and the long term wear period. The retention
      force value and the force-distance integral of the first 0.33 mm of each cycle
      were calculated. RESULTS: The retentive forces were significantly higher for
      group E and the integrals were significantly lower for this group except the
      integral at cycle 10,000. The changes of retention force and integral did not
      differ significantly between both groups in all phases. The change of the
      integrals as well as the integral at the particular cycles showed higher
      interquartile distances for group C. CONCLUSIONS: Within the limitations of this
      study the tested conical crowns showed clinically acceptable retentive
      properties. The values reached a range comparable to retentive elements tested in
      recent literature. The values of group C showed higher ranges. The force measured
      for group E was significantly higher than for group C but the integrals showed an
      opposite tendency. The results indicate that an exclusive analysis of the force
      is not sufficient as the integral is not equivalent to the force although it
      describes the retentive property of the system in a better way than the force
      over a distance is described. Both systems seem to be suitable for clinical
      practice.

PMID- 22858709
TI  - Newly forming bone graft: a novel surgical approach to the treatment of denuded
      roots.
AB  - Many techniques have been proposed for root coverage. However, none of them
      presents predictable results in deep and wide recessions. OBJECTIVES: The aim of
      this case series report is to describe an alternative technique for root coverage
      at sites showing deep recessions and attachment loss >4 mm at buccal sites.
      MATERIAL AND METHODS: Four patients presenting deep recession defects at buccal
      sites (>4 mm) were treated by the newly forming bone graft technique, which
      consists in the creation of an alveolar socket at edentulous ridge and
      transferring of granulation tissue present in this socket to the recession defect
      after 21 days. Clinical periodontal parameters, including recession depth (RD),
      probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP),
      plaque index (PI) and keratinized gingiva width (KGW) were evaluated by a single
      examiner immediately before surgery and at 1, 3, 6 and 9 months postoperatively.
      RESULTS: All cases showed reduction in RD and PD, along with CAL gain, although
      no increase in KGW could be observed. These findings suggest that the technique
      could favor periodontal regeneration along with root coverage, especially in
      areas showing deep recessions and attachment loss.

PMID- 22858710
TI  - Solitary nonfamilial desmoplastic trichoepithelioma of the external auditory
      canal.

PMID- 22858711
TI  - Objective skills assessment and construct validation of a virtual reality
      temporal bone simulator.
AB  - OBJECTIVES: To evaluate construct validity of the Voxelman TempoSurg Virtual
      Reality (VR) temporal bone simulator by determining whether generated objective
      metrics can distinguish experienced otologic surgeons from intermediate and
      novice surgeons. DESIGN: Prospective assessment study. SETTING: Two university
      affiliated teaching hospitals. PARTICIPANTS: Sixty-five participants were
      recruited; 40 novice surgeons, 15 trainees in otolaryngology, and 10 experienced
      otolaryngology consultants with a specialist interest in otology were
      individually assessed on a standardized simulated temporal bone task. The task
      involved identification and delineation of the sigmoid sinus in a virtual left
      sided temporal bone. MAIN OUTCOME MEASURES: Objective data were produced using a
      scoring matrix incorporated into the VOXEL MAN TempoSurg software. The simulator
      measured the total time taken to complete the task, the volume and efficiency of
      bone removal and error data for excessive force or injury to the facial nerve,
      dura, and sigmoid sinus. RESULTS: Experts and intermediates outperformed novices
      with respect to the total time taken to complete the task (expert versus novice:
      p < 0.001; intermediate versus novice: p < 0.001), total volume of bone removed
      (p < 0.001 and p = 0.03), efficiency of bone removal (p < 0.001 and p < 0.001),
      time spent with the drill tip obscured (p = 0.002 and p < 0.001), and number of
      injuries to the sigmoid sinus (p < 0.001 and p < 0.001). The intermediate group
      injured the sigmoid sinus on more occasions than the experts (p = 0.008) and were
      less efficient than experienced surgeons (p = 0.005). CONCLUSION: Simulator
      generated objective metrics can be used to differentiate individuals of differing
      levels of experience using a standardized temporal bone task. VR simulation has
      potential as a training tool and may have a role in both formative and summative
      assessment.

PMID- 22858712
TI  - The value of HRCT in stapes fixations corresponding to hearing thresholds and
      histologic findings.
AB  - OBJECTIVE: To estimate the correlations between high-resolution computed
      tomography (HRCT) scans, preoperative audiometric findings and histopathologic
      results in stapes ankylosis. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: A total of 57 patients with stapes ankylosis,
      who underwent unilateral stapedectomies were analyzed. INTERVENTIONS: Diagnostic
      and therapeutic. MAIN OUTCOME MEASURES: Preoperative HRCT examinations were
      performed in all cases. Findings of HRCT were categorized according to Marshall's
      grading system. Preoperative air-bone gaps (ABGs) and bone conduction (BC)
      thresholds were determined. Stapes footplates removed surgically were processed
      using hematoxylin and eosin staining. RESULTS: Active otosclerosis (n = 29) was
      demonstrated by HRCT with a sensitivity of 76.31%, whereas its sensitivity to
      establish inactive otosclerosis (n = 13, 61.9%) and nonotosclerotic stapes
      fixations (n = 15, 51.7%) was much lower. Nonotosclerotic stapes fixations were
      characterized by pure conductive hearing loss that was not associated with HRCT
      findings. HRCT grades showed statistically significant association with BC levels
      at the averages of 0.5-1-2 kHz frequencies in the group of ears with inactive
      otosclerosis, exclusively (p < 0.05). CONCLUSION: HRCT is a reliable imaging
      method in the preoperative diagnosis of different types of stapes fixations.
      Imaging findings should be evaluated together with clinical history and
      audiometric data for obtaining as precise diagnosis for stapes fixation as
      possible.

PMID- 22858713
TI  - Ocular and cervical vestibular-evoked myogenic potentials in Tumarkin falls.
AB  - OBJECTIVE: This study applied ocular vestibular-evoked myogenic potential (oVEMP)
      and cervical VEMP (cVEMP) tests in Meniere's patients with Tumarkin falls to
      investigate the etiologic role of the saccule/utricle in the event of Tumarkin
      falls. STUDY DESIGN: Retrospective study. SETTING: University hospital. SUBJECTS:
      Twenty unilateral definite Meniere's patients were divided into 2 age- and sex
      matched groups. Ten patients had a history of drop attacks, and 10 had no history
      of drop attacks. MAIN OUTCOME MEASURES: All patients underwent audiometry and
      caloric, oVEMP, and cVEMP tests. RESULTS: No significant differences were
      observed between the fall and nonfall groups in terms of Meniere staging, and
      caloric and cVEMP test results. In the fall group, oVEMP test via Fz tapping
      showed augmented, reduced, and absent responses in 1, 1, and 8 patients,
      respectively. In 3 of the latter 8 patients, however, oVEMPs could be obtained by
      lateral mastoid tapping. Thus, 100% of patients in the fall group had abnormal
      oVEMPs, which significantly differed from 50% oVEMP abnormalities in the nonfall
      group. Comparison of the abnormal results for the caloric, oVEMP, and cVEMP tests
      revealed that poorer residual vestibular function in the fall group than the
      nonfall group. CONCLUSION: Absence of oVEMP by Fz tapping and presence of oVEMPs
      via lateral tapping indicates a residual utricular function. With residual canal
      function (canal paresis) and absent cVEMPs, subsequently residual utricular
      function may trigger the Tumarkin falls in Meniere's patients.

PMID- 22858714
TI  - Radiographic association of schwannomas with sensory ganglia.
AB  - OBJECTIVE: Clinical experience suggests that the majority of schwannomas arise
      within sensory ganglia, suggesting that intraganglionic glial cells represent a
      potential cell of origin for schwannomas. To support this clinical impression, we
      reviewed magnetic resonance imaging (MRI) studies performed over a 5-year period
      at our institution to determine the relationship of cranial and spinal nerve
      schwannomas with the ganglia of the associated nerves. STUDY DESIGN:
      Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Patients
      undergoing imaging study at our institution over a 5-year period.
      INTERVENTION(S): Radiographic images at our institution were reviewed as well as
      published studies to determine the anatomic location of schwannomas. MAIN OUTCOME
      MEASURE(S): Anatomic location of schwannomas. RESULTS: A total of 372 patients
      were found over the 5-year study period, 31 of those were diagnosed with
      neurofibromatosis Type 2 (NF2). Vestibular schwannomas comprised the greatest
      number of schwannomas, followed by spinal schwannomas. In NF2 patients, spinal
      schwannomas were the most common tumor, followed by vestibular schwannomas. In
      NF2 patients and those with sporadic schwannomas, the overwhelming majority of
      tumors arose in nerves with a sensory component and were associated with the
      sensory ganglia of the nerves (562/607, 92.6%). Very few tumors arose from pure
      motor nerves. This is supported by review of published articles on anatomic
      location of schwannomas. CONCLUSION: Schwannomas are strongly associated
      anatomically with the ganglia of sensory nerves. These findings raise the
      possibility that intraganglionic glial cells give rise to the majority of
      schwannomas.

PMID- 22858716
TI  - Characteristics of patients with unilateral and bilateral Meniere's disease.
AB  - OBJECTIVE: To evaluate epidemiologic differences between patients with unilateral
      and bilateral Meniere's disease (MD). To evaluate these differences for insights
      into the possible causes of bilateral MD. BACKGROUND: The diagnosis of MD is
      based on clinical criteria, and its cause is unknown. Differences in
      characteristics of patients with unilateral and bilateral MD have been noted, but
      these studies' diagnostic criteria have been variable. To delineate findings that
      might have implications as to the cause of MD, we have studied rigidly selected
      patient populations with unilateral and bilateral MD STUDY DESIGN: Prospective
      cohort. MATERIALS AND METHODS: Patients with a potential diagnosis of MD
      underwent extensive evaluations (audiometric, radiologic, and immunologic), and
      only patients with idiopathic MD were included in this study. Bilaterality of
      disease was based on clinical and audiometric criteria. Variables identified as
      part of the evaluation were subjected to statistical analyses to determine if
      significant differences existed in the characteristics of patients in the
      unilateral and bilateral groups RESULTS: Patients with bilateral disease
      presented at a significantly younger age and had a significantly higher incidence
      of a personal history of migraines and a family history of MD. None of the other
      identified variables were found to be significantly different. CONCLUSION:
      Patients with bilateral MD have a higher incidence of migraines and of a family
      history of MD. Implications as to disease pathogenesis are discussed.

PMID- 22858715
TI  - A randomized, double-blind, placebo-controlled clinical study to assess safety
      and clinical activity of OTO-104 given as a single intratympanic injection in
      patients with unilateral Meniere's disease.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and clinical activity of a
      single intratympanic injection of OTO-104, sustained-release dexamethasone
      formulation, in patients with unilateral Meniere's disease. STUDY DESIGN:
      Prospective, double-blind, randomized, placebo-controlled, dose-escalation study
      of 16 weeks' (4-wk lead-in before dosing; 12-wk follow-up after dosing) duration
      for each patient. SETTING: Fifteen centers (physician offices and academic or
      tertiary referral centers). PATIENTS: Forty-four patients aged 22 to 75 years.
      INTERVENTION: Single intratympanic injection of OTO-104 (3 or 12 mg) or placebo.
      MAIN OUTCOME MEASURES: Safety and tolerability were assessed via adverse event
      reports, otoscopy, audiometry, and tympanometry. Clinical activity was assessed
      primarily as changes in vertigo frequency. RESULTS: OTO-104 was well tolerated,
      with no impact on hearing function. Plasma levels were observed in a few patients
      and were barely quantifiable. The most frequently reported adverse event
      considered related to investigational product was tympanic membrane perforation;
      no clinical sequelae were associated with these perforations and all were graded
      mild or moderate. At Month 3, the observed mean +/- standard deviation (SD)
      change from baseline in vertigo frequency was -0.124 +/- 0.153, -0.147 +/- 0.166,
      and -0.211 +/- 0.153 for the placebo, 3-mg OTO-104, and 12-mg OTO-104 groups,
      respectively; corresponding to 42%, 56% and 73% reductions in vertigo frequency,
      respectively. Similar results were observed for tinnitus, measured by the
      Tinnitus Handicap Inventory (THI-25). CONCLUSION: OTO-104 was safe and well
      tolerated. Although the sample size was small, the data suggest 12 mg of OTO-104
      was associated with a clinically meaningful reduction in vertigo frequency
      compared to placebo 3 months after treatment.

PMID- 22858717
TI  - Vertigo and stroke:  a national database survey.
AB  - OBJECTIVE: To investigate the association between vertigo and stroke in Taiwan
      using the Bureau of National Health Insurance research database. METHODS:
      Information on adult patients with an index vertigo attack in 2006 was retrieved
      from Bureau of National Health Insurance research database. All patients with
      specific diagnostic codes for vertigo were included. Occurrence of stroke during
      a 1-year follow-up period was identified. Risk factors for stroke were examined.
      Using chi test, t test, and a multilevel logistic regression model, patients with
      vertigo were categorized into stroke and nonstroke groups for comparative
      analyses. An age- and sex- matched control cohort was prepared for comparison.
      RESULTS: Patients with vertigo (n = 527,807) (mean age, 55.1 yr) accounted for
      3.1% of the general Taiwanese adult population. The prevalence of stroke among
      vertigo patients of 0.5% (mean age, 67.8 yr) was slightly higher than that of the
      control group (0.3%; mean age, 72.3 yr; p < 0.0001). The types of stroke were
      ischemic (66.7%), nontypical (29.0%), and hemorrhage (4.3%). The prevalence of
      stroke increased with age (p < 0.001). Patients with vertigo had higher
      prevalence of comorbid conditions (p < 0.0001); those with diabetes mellitus,
      hypertension, dyslipidemia, coronary artery disease, or atrial fibrillation had a
      higher prevalence of stroke (p < 0.001). Hypertension was the most significant
      predictor of stroke (odds ratio, 3.77; 95% confidence interval, 3.36-4.23; p <
      0.001). CONCLUSION: Patients with vertigo had higher chance to develop stroke
      than the control group. Some strokes may initially manifest as peripheral
      vertigo, and some central vertigo may eventually evolve into a stroke. Middle
      aged male, diabetes, hypertension, dyslipidemia, coronary artery disease, and
      atrial fibrillation are risk factors for subsequent stroke in vertigo patients.

PMID- 22858718
TI  - An unprecedented "linear-bent" isomerism in tri-nuclear Cu2(II)Zn(II) complexes
      with a salen type di-Schiff base ligand.
AB  - Two new trinuclear hetero-metallic copper(II)-zinc(II) complexes
      [(CuL)(2)Zn(N(3))(2)] (1A and 1B) have been synthesized using [CuL] as a so
      called "metalloligand" (where H(2)L = N,N'-bis(salicylidene)-1,3-propanediamine)
      and structurally characterized. Complexes 1A and 1B have the same molecular
      formula but crystallize in different crystal systems (triclinic for 1A and
      monoclinic for 1B) with space group P1 for 1A and P2(1)/c for 1B. 1A is an
      angular trinuclear species, in which two terminal four-coordinate square planar
      "metalloligand" [CuL] are coordinated to a central Zn(II) through double
      phenoxido bridges. The Zn(II) is in a six-coordinate distorted octahedral
      environment being bonded additionally to two mutually cis nitrogen atoms of
      terminal azide ions. In complex 1B, in addition to the double phenoxido bridge,
      the two terminal Cu(II) ions are linked to the central Zn(II) via a MU(-l,l)
      azido bridge giving rise to a square pyramidal environment around the Cu(II) ions
      and consequently the structure becomes linear. These two species can be
      considered as "linear-bent" isomers. EPR spectra and ESI mass spectra show that
      the two isomers are identical in solution. The DFT calculation reveals that the
      energy of 1A is 7.06 kcal mol(-1) higher than that of 1B. The existence of both
      isomers in the solid state suggests that crystal packing interactions in are more
      efficient and probably compensate for the difference in energy.

PMID- 22858720
TI  - Lithium-ion batteries based on vertically-aligned carbon nanotube electrodes and
      ionic liquid electrolytes.
AB  - In conjunction with environmentally benign ionic liquid electrolytes, vertically
      aligned carbon nanotubes (VA-CNTs) sheathed with and without a coaxial layer of
      vanadium oxide (V(2)O(5)) were used as both cathode and anode, respectively, to
      develop high-performance and high-safety lithium-ion batteries. The VA-CNT anode
      and V(2)O(5)-VA-CNT cathode showed a high capacity (600 mAh g(-1) and 368 mAh g(
      1), respectively) with a high rate capability. This led to potential to achieve a
      high energy density (297 Wh kg(-1)) and power density (12 kW kg(-1)) for the
      prototype batteries to significantly outperform the current state-of-the-art Li
      ion batteries.

PMID- 22858719
TI  - Regions of homozygosity identified by SNP microarray analysis aid in the
      diagnosis of autosomal recessive disease and incidentally detect parental blood
      relationships.
AB  - PURPOSE: The purpose of this study was to document the ability of single
      nucleotide polymorphism microarray to identify copy-neutral regions of
      homozygosity, demonstrate clinical utility of regions of homozygosity, and
      discuss ethical/legal implications when regions of homozygosity are associated
      with a parental blood relationship. METHODS: Study data were compiled from
      consecutive samples sent to our clinical laboratory over a 3-year period. A
      cytogenetics database identified patients with at least two regions of
      homozygosity >10 Mb on two separate chromosomes. A chart review was conducted on
      patients who met the criteria. RESULTS: Of 3,217 single-nucleotide polymorphism
      microarrays, 59 (1.8%) patients met inclusion criteria. The percentage of
      homozygosity ranged from 0.9 to 30.1%, indicating parental relationships from
      distant to first-degree relatives. First-degree kinship was suspected in the
      parents of at least 11 patients with regions of homozygosity covering >21.3% of
      their autosome. In four patients from two families, homozygosity mapping
      discovered a candidate gene that was sequenced to identify a clinically
      significant mutation. CONCLUSION: This study demonstrates clinical utility in the
      identification of regions of homozygosity, as these regions may aid in diagnosis
      of the patient. This study establishes the need for careful reporting, thorough
      pretest counseling, and careful electronic documentation, as microarray has the
      capability of detecting previously unknown/unreported relationships.

PMID- 22858721
TI  - Direct participation of counter anion in acid hydrolysis of glycoside.
AB  - The mechanism of acid hydrolysis of glycoside has been investigated since the end
      of the 19th century accompanied by lots of literatures published on the
      mechanism, although little attention has surprisingly been paid to the action of
      counter anion of acid. In this paper, it was investigated whether or not counter
      anion of acid directly participates in acid hydrolysis of glycosides, methyl
      alpha- and beta-D-glucopyranosides (MGP) in water, aqueous 74%, and 82% 1,4
      dioxane systems. Because proton activity of a reaction system is the important
      rate-determining parameter in the universally acknowledged mechanism, it was
      carefully estimated in this study. The results suggested that bromide anion
      directly participates in the acid hydrolysis reaction of MGP in a water solvent
      system and the participation of bromide anion is further pronounced in aqueous
      74% and 82% 1,4-dioxane solvent systems. It was also suggested that chloride
      anion directly participates in these dioxane solvent systems.

PMID- 22858722
TI  - A novel empirical mutual information approach to identify co-evolving amino acid
      positions of influenza A viruses.
AB  - Mutual information (MI) is an approach commonly used to estimate the evolutionary
      correlation of 2 amino acid sites. Although several MI methods exist, prior to
      our contribution no systematic method had been developed to assess their
      performance, or to establish numerical thresholds to detect co-evolving amino
      acid sites. The current study performed a Markov chain Monte Carlo (MCMC)
      algorithm on influenza viral sequences to capture their evolutionary
      characteristics. A consensus maximum clade credibility (MCC) tree was estimated
      from the samples, together with their amino acid substitution statistics, from
      which we generated synthetic sequences of known dependent and independent paired
      amino acid sites. A pair-to-pair and influenza-specific amino acid substitution
      matrix (P2PFLU) incorporated into Bayesian Evolutionary Analysis Sampling Trees
      (BEAST) enumerated these synthetic sequences. The sequences inherited
      evolutionary features and co-varying characteristics from the real viral
      sequences, rendering these synthetic data ideal for exploring their co-evolving
      features. For the MI measure, we proposed a novel metric called the empirical MI
      (MI(Em)), which outperformed other MI measures in analysis of receiver operating
      characteristics (ROC). We implemented our approach on 1086 all-time PB2 sequences
      of influenza A H5N1 viruses, in which we found 97 sites exhibiting co
      evolutionary substitution of one or more amino acid sites. In particular, PB2
      451, along with eight other PB2 sites of various MI(Em) scores, was found to co
      evolve with PB2 627, a known species-associated amino acid residue which plays a
      critical role in influenza virus replication.

PMID- 22858723
TI  - The use of spectroscopic imaging and mapping techniques in the characterisation
      and study of DLD-1 cell spheroid tumour models.
AB  - Determining the chemical and biological compositions of the tumour models used in
      pharmacological studies is crucial for understanding the interactions between the
      drug molecules and the tumour micro-environment. Conventional techniques for
      spheroid characterisation require intensive chemical pre-treatments that result
      in the removal of unbound metabolites. In this study, the spectroscopic
      techniques, scanning transmission ion microscopy (STIM), proton-induced X-ray
      emission (PIXE) mapping, scanning X-ray fluorescence microscopy (SXFM), and
      Fourier transform infrared (FT-IR) imaging were employed to gain complementary
      information on the compositions of untreated DLD-l cancer cell spheroids. When
      used together, these techniques exhibited great potential for providing a
      comprehensive over-view of the density, biochemistry and elemental compositions
      within the different regions of the spheroids. STIM density and elemental maps
      correlated well with cellular density across the spheroid, and showed the
      accumulation of S, Cu and various lighter elements in the necrotic region. High
      levels of oxidative stress were evident in the hypoxic region, and different
      degrees of cellular necrosis as well as high levels of lactate and collagen
      within the necrotic region were suggested by FT-IR markers. FT-IR imaging was
      further employed to study the pharmacodynamics of known the cytotoxins, cisplatin
      and Pt1C3. Cisplatin was observed to induce minimal biochemical changes to the
      spheroids following 24 hour incubations, whereas Pt1C3 caused severe cellular
      damage to the spheroid periphery; consistent with their different modes of
      action.

PMID- 22858724
TI  - IL1B and VWF variants are associated with fibrinolytic early recanalization in
      patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: There is a great interindividual variability among
      patients with acute ischemic stroke regarding the response to intravenous tissue
      type plasminogen activator treatment. The aim of this study was to identify
      genetic variants associated with recanalization, and thus treatment efficacy,
      after tissue-type plasminogen activator administration. METHODS: A total of 140
      single nucleotide polymorphisms from 97 candidate genes were successfully
      genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited
      tissue-type plasminogen activator-treated patients, of whom 33% recanalized
      during tissue-type plasminogen activator infusion. Functional studies were then
      performed, including assessment of interleukin 1B mRNA levels and von Willebrand
      factor, FIII, FVII, FVIII, and FX protein activity. RESULTS: After replication,
      the following single nucleotide polymorphisms were associated with early
      recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers:
      32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of
      recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and
      rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%;
      P=0.006; replication cohort: P=0.046). The functional studies revealed an
      association between the rs1063856 single nucleotide polymorphisms in vWF and
      FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). CONCLUSIONS:
      Three single nucleotide polymorphisms were associated with tissue-type
      plasminogen activator efficacy in the Spanish population, and their mechanism of
      action might be associated with the activity of coagulation factors.

PMID- 22858725
TI  - Improving recovery after stroke: a role for antidepressant medications?

PMID- 22858726
TI  - Comparison of computed tomography perfusion and magnetic resonance imaging
      perfusion-diffusion mismatch in ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Perfusion imaging has the potential to select patients
      most likely to respond to thrombolysis. We tested the correspondence of computed
      tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion
      diffusion magnetic resonance imaging (MRI). METHODS: Acute ischemic stroke
      patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1
      hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak
      of the deconvolved tissue residue function (Tmax) were calculated. The diffusion
      lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually
      outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct
      core (compared with diffusion-weighted imaging) was tested. To reduce false
      positive low CBF regions, relCBF core was restricted to voxels within a relative
      time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6
      seconds perfusion lesion was automatically segmented and registered to CTP.
      Receiver-operating characteristic analysis determined the optimal CT-Tmax
      threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR
      perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio
      >1.2, absolute mismatch >10 mL, infarct core <70 mL). RESULTS: In analysis of 49
      patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining
      relCBF <31% within the automated relTTP perfusion lesion region of interest
      reduced the median magnitude of volumetric error (vs diffusion-weighted imaging)
      from 47.5 mL to 15.8 mL (P<0.001). The optimal CT-Tmax threshold to match MR-Tmax
      >6 seconds was 6.2 seconds (95% confidence interval, 5.6-7.3 seconds;
      sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6
      seconds "penumbra" and relTTP-constrained relCBF "core," CT-based and MRI-based
      mismatch status was concordant in 90% (kappa=0.80). CONCLUSIONS: Quantitative CTP
      mismatch classification using relCBF and Tmax is similar to perfusion-diffusion
      MRI. The greater accessibility of CTP may facilitate generalizability of mismatch
      based selection in clinical practice and trials.

PMID- 22858727
TI  - Cerebral white matter lesions and lacunar infarcts contribute to the presence of
      mild parkinsonian signs.
AB  - BACKGROUND AND PURPOSE: Mild parkinsonian signs (MPS) are common in elderly
      people and may be an early stage of parkinson(ism). They might be related to
      cerebral small-vessel disease, although this association remains incompletely
      understood. To identify subjects at early stages of the disease, we investigated
      whether the presence of MPS was dependent on the severity and location of small
      vessel disease, including white matter lesions and lacunar infarcts. METHODS:
      Four hundred thirty individuals, with small-vessel disease, aged between 50 and
      85 years, without dementia or parkinsonism, were included in this analysis and
      underwent MRI scanning. The number and location of lacunar infarcts were rated.
      White matter lesion volume was assessed by manual segmentation with automated
      delineating of different regions. Presence of MPS was based on the motor section
      of the Unified Parkinson's Disease Rating Scale. Associations were determined
      using logistic regression analysis adjusted for age, sex, and total brain volume.
      RESULTS: Severe white matter lesions and the presence of lacunar infarcts were
      independently associated with the presence of MPS (OR, 2.6; 95% CI, 1.3-4.9 and
      OR, 1.8; 95% CI, 1.0-3.0). Frontal and parietal white matter lesions and, to a
      lesser extent, lacunar infarcts in the thalamus were associated with a higher
      risk of MPS. The presence of lacunar infarcts was independently related to the
      bradykinesia category of parkinsonian signs. CONCLUSIONS: This study shows that
      severe small-vessel disease, especially at certain locations, is associated with
      MPS signs in older adults. Our findings suggest that small-vessel disease
      interrupts basal ganglia-thalamocortical circuits involving both the frontal and
      parietal lobes and hence may result in MPS.

PMID- 22858728
TI  - Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial
      fibrillation: a science advisory for healthcare professionals from the American
      Heart Association/American Stroke Association.

PMID- 22858729
TI  - SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to provide a simple and
      practical clinical classification for the etiology of intracerebral hemorrhage
      (ICH). METHODS: We performed a retrospective chart review of consecutive patients
      with ICH treated at the Helsinki University Central Hospital, January 2005 to
      March 2010 (n=1013). We classified ICH etiology by predefined criteria as
      structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic
      disease (S), hypertension (H), or undetermined (U). Clinical and radiological
      features and mortality by SMASH-U (Structural lesion, Medication, Amyloid
      angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were
      analyzed. RESULTS: Structural lesions, namely cavernomas and arteriovenous
      malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5%
      (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid
      angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology
      remained undetermined in 21%. Interrater agreement in classifying cases was high
      (kappa, 0.89; 95% CI, 0.82-0.96). Patients with structural lesions had the
      smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month
      mortality 4%), whereas anticoagulation-related ICHs were largest (13.4 mL) and
      most often fatal (54%). Overall, median ICH survival was 5&frac12; years, varying
      strongly by etiology (P<0.001). After adjustment for baseline characteristics,
      patients with structural lesions had the lowest 3-month mortality rates (OR,
      0.06; 95% CI, 0.01-0.37) and those with anticoagulation (OR, 1.9; 1.0-3.6) or
      other systemic cause (OR, 4.0; 1.6-10.1) the highest. CONCLUSIONS: In our
      patients, performing the SMASH-U classification was feasible and interrater
      agreement excellent. A plausible etiology was determined in most patients but
      remained elusive in one in 5. In this series, SMASH-U based etiology was strongly
      associated with survival.

PMID- 22858730
TI  - Partner burden in irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Studies have described the burden experienced by caregivers
      and next of kin to patients with diseases such as cancer. However, the burden of
      functional gastrointestinal disorders on partners of patients has not been
      determined. We aimed to quantify the degree of burden to partners of patients
      with irritable bowel syndrome (IBS), to describe the factors that affect the
      burden perceived, and to identify the areas of relationship that are affected.
      METHODS: We surveyed 152 patients diagnosed with IBS at a tertiary
      gastrointestinal clinic, on the basis of Rome III criteria, and their partners.
      Their partners completed questionnaires including the Zarit Burden Interview
      (ZBI), Relationship Satisfaction Scale, and questions on sexual relationships.
      Patients with IBS were rated for disease severity by using the Functional Bowel
      Disease Severity Index. We compared findings with those from 39 partners of
      healthy individuals (controls). RESULTS: There were no significant demographic
      differences between the partners of patients with IBS and controls; demographics
      had no effect on burden. Burden was significantly higher among partners of IBS
      patients (mean ZBI score, 22.1) than controls (mean ZBI score, 11.5) (P = .0002).
      The degree of burden was directly related to IBS severity (P < .0001). There were
      inverse relationships between partners' rating of burden (ZBI) and relationship
      quality (R = -0.60; P < .001) and sexual satisfaction (R = -0.56; P < .0001).
      There was no difference in the Relationship Satisfaction Scale scores (4.25 vs
      4.19; P = .78) or sexual relationship (6.47 vs 6.21; P = .64) between partners of
      IBS patients and controls, respectively. CONCLUSIONS: Partners of patients with
      IBS have a significant burden (on the basis of ZBI score), compared with partners
      of healthy individuals. Perceived burden increases with IBS severity and poorer
      sexual and relationship satisfaction.

PMID- 22858731
TI  - Management of intestinal complications in patients with pelvic radiation disease.
AB  - Gastrointestinal toxicity after radiotherapy for pelvic cancer is a major
      complication-the most commonly reported symptoms include rectal bleeding,
      diarrhea, and fecal incontinence, which substantially impair patients' quality of
      life. Management of these symptoms can be a challenge, although available
      treatment strategies generally are ignored or underused. Radiation-induced
      symptoms have multiple mechanisms of pathogenesis; the first step for the correct
      management is to identify the mechanism that is causing the symptoms. Optimal
      management requires close liaisons among physicians, gastroenterologists with
      specialist interests, radiotherapists, oncologists, dieticians, nurses, and
      surgeons. Patients should be reassured that treatment options (medical,
      endoscopic, and surgical) exist and are in most cases successful if patients are
      referred to experts in pelvic radiation disease. However, although new
      therapeutic approaches are not yet always supported by high-quality trials,
      research projects are underway to improve management of patients. Clinicians
      should focus on using proven treatments correctly and avoiding misuse.

PMID- 22858732
TI  - Liver biopsy has a low diagnostic performance for intermediate stages of
      fibrosis.

PMID- 22858733
TI  - A polyplex qPCR-based binding assay for protein-DNA interactions.
AB  - The measurement of protein-DNA interactions is difficult and often involves
      radioisotope-labelled DNA to obtain the desired assay sensitivity. More recently,
      high-throughput proteomic approaches were developed but they generally lack
      sensitivity. For these methods, the level of technical difficulties involved is
      high due to the need for specialised facilities or equipment and training. The
      new qPCR-based DNA-binding assay involves immunoprecipitation of a GFP-tagged DNA
      binding protein in complex with various DNA targets (Ter sites) followed by qPCR
      quantification, affording a very sensitive and quantitative method that can be
      performed in polyplex. Using a single binding reaction, the binding specificity
      of the DNA replication terminator protein Tus for ten termination sites TerA-J
      could be obtained for the first time in just a few hours. This new qPCR DNA
      binding assay can easily be adapted to determine the binding specificity of
      virtually any soluble and functional epitope-tagged DNA-binding protein.

PMID- 22858734
TI  - Role of heat shock protein 27 in gemcitabine-resistant human pancreatic cancer:
      comparative proteomic analyses.
AB  - The most notable obstacle hindering the effective treatment of human pancreatic
      cancer is intrinsic chemoresistance. In order to identify the candidate
      protein(s) responsible for the intrinsic chemoresistance, the protein expression
      profiling of human pancreatic adenocarcinoma cell line Capan-1 and its distinct
      surviving cells following primary treatment with gemcitabine (GEM) were compared
      by two-dimensional electrophoresis (2-DE) combined with liquid chromatography
      mass spectrometry (LC-MS) or mass spectrometry (MS). In total, nine proteins were
      identified, and heat shock protein B1 (HSP27), one of the differentially
      expressed proteins, was selected for further validation. Furthermore, the results
      of western blotting and immunohistochemical staining indicated that HSP27 may be
      significant in pancreatic intrinsic chemoresistance to GEM. The findings of this
      study provide a platform for further elucidation of the underlying mechanisms of
      pancreatic cancer intrinsic chemoresistance and demonstrate that HSP27 may be a
      valid target for anticancer drug development.

PMID- 22858735
TI  - Accuracy of Timed Up and Go Test for screening risk of falls among community
      dwelling elderly.
AB  - OBJECTIVE: To determine the accuracy of the Timed Up and Go Test (TUGT) for
      screening the risk of falls among community-dwelling elderly individuals. METHOD:
      This is a prospective cohort study with a randomly by lots without reposition
      sample stratified by proportional partition in relation to gender involving 63
      community-dwelling elderly individuals. Elderly individuals who reported having
      Parkinson's disease, a history of transitory ischemic attack, stroke and with a
      Mini Mental State Exam lower than the expected for the education level, were on a
      wheelchair and that reported a single fall in the previous six months were
      excluded. The TUGT, a mobility test, was the measure of interested and the
      occurrence of falls was the outcome. The performance of basic activities of daily
      living (ADL) and instrumental activities of daily living (IADL) was determined
      through the Older American Resources and Services, and the socio-demographic and
      clinical data were determined through the use of additional questionnaires.
      Receiver Operating Characteristic Curves were used to analyze the sensitivity and
      specificity of the TUGT. RESULTS: Elderly individuals who fell had greater
      difficulties in ADL and IADL (p<0.01) and a slower performance on the TUGT
      (p=0.02). No differences were found in socio-demographic and clinical
      characteristics between fallers and non-fallers. Considering the different
      sensitivity and specificity, the best predictive value for discriminating elderly
      individuals who fell was 12.47 seconds [(RR=3.2) 95%CI: 1.3-7.7]. CONCLUSIONS:
      The TUGT proved to be an accurate measure for screening the risk of falls among
      elderly individuals. Although different from that reported in the international
      literature, the 12.47 second cutoff point seems to be a better predictive value
      for Brazilian elderly individuals.

PMID- 22858736
TI  - Analysis of reporting of systematic reviews in physical therapy published in
      Portuguese.
AB  - BACKGROUND: Systematic reviews are considered the best design to synthesize all
      existing information of a given research topic. To date, there is no study that
      investigated the quality of reporting of systematic reviews relevant to physical
      therapy published in Portuguese. OBJECTIVE: To analyse the quality of reporting
      of systematic reviews in the field of physical therapy published in Portuguese by
      using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analysis) checklist. METHOD: All systematic reviews published in Portuguese that
      were indexed on PEDro database up to August 2011 were included. The quality of
      reporting of the eligible papers was analysed by using the PRISMA checklist. Each
      quality assessment was performed by two independent reviewers with arbitration of
      a third reviewer if necessary. RESULTS: A total of 37 systematic reviews were
      identified. These studies were published between 2003 and 2010. Less than 30% of
      the PRISMA checklist items were satisfied, being most of the items related to the
      introduction and discussion sections. No improvements over time were observed.
      CONCLUSIONS: Most of the studies did not satisfy the items from the PRISMA
      Checklist. It seems that most of authors did not know the existence of this
      checklist. The implementation of reporting statements such as the PRISMA
      statement by Portuguese-written journals is likely to help authors to write their
      systematic reviews in a more transparent and clear way.

PMID- 22858737
TI  - Analysis of angular reading distortions of photographic images.
AB  - BACKGROUND: Although photogrammetry is a widespread technique in the health
      field, despite of the methodological efforts distortions in the angular readings
      of the images are common. OBJECTIVE: To measure the error of angular measurements
      in photo images with different digital resolutions in an object with pre
      determined angles. METHODS: We used a rubber ball with 52 cm in circumference.
      The object was previously marked with angles of 10 degrees , 30 degrees , 60
      degrees  and 90 degrees  degrees. The photographic records were performed with
      the focal axis of the camera perpendicular and three meters away from the object,
      without the use of optical zoom and a resolution of 3, 5 and 10 Megapixels (Mp).
      All photographic records were stored and a previously trained experimenter using
      the computer program ImageJ analyzed the angular values of each photo. The
      measurements were performed twice within a fifteen-days interval. Subsequently,
      we calculated the accuracy, relative error and error in degrees values, precision
      and the Intraclass Correlation Coefficient (ICC). RESULTS: When analyzing the
      angle of 10 degrees , the average accuracy of measurements was higher for those
      records of 3 Mp resolution compared to 5 and 10 Mp resolutions. The ICC was
      considered excellent for all resolutions. With regards to the analyzed angles in
      photographic records, it was possible to verify that the 90-degree angle
      photographs were more accurate, had lower relative error and error in degrees,
      and were more precise, regardless of image resolution. CONCLUSION: The
      photographs records that were taken with a 3 Mp resolution provided great
      accuracy and precision measurements and lower errors values, suggesting to be the
      proper resolution to generate image of angles of 10o and 30o.

PMID- 22858738
TI  - Effect of lanthanum substitution at A site on structure and enhanced properties
      of new Aurivillius oxide K0.25Na0.25La0.5Bi2Nb2O9.
AB  - Aurivillius ferroelectrics K(0.25)Na(0.25)La(0.5)Bi(2)Nb(2)O(9) (KNBN-La) and
      K(0.25)Na(0.25)Bi(2.5)Nb(2)O(9) (KNBN-Bi) were prepared by using solid-state
      reaction process. Rietveld refinements for the KNBN-La and KNBN-Bi were carried
      out by using powder X-ray diffraction at room temperature and they were confirmed
      to be two-layer Aurivillius oxides with orthorhombic space group A2(1)am. The
      lattice parameters are a = 5.50468(10) A, b = 5.49217(10) A, and c = 25.05108(35)
      A for KNBN-La and a = 5.48867(6) A, b = 5.47895(6) A, and c = 25.10591(25) A for
      KNBN-Bi. Lanthanum (La(3+)) substitution for bismuth (Bi(3+)) led to an
      enhancement in relaxation behavior for the KNBN-La ceramics, with a ferroelectric
      to paraelectric phase transition temperature (T(c)) of about 360  degrees C. The
      KNBN-La ceramics had a high remnant polarization (P(r)) of 13.6 MUC cm(-2) and a
      field-induced strain of up to 0.031%. Particularly, the decrease in P(r) for the
      KNBN-La ceramics after 10(8) cumulative switching cycles was only 6%.

PMID- 22858739
TI  - Conductive metal-organic frameworks and networks: fact or fantasy?
AB  - Electrical conduction is well understood in materials formed from inorganic or
      organic building blocks, but their combination to produce conductive hybrid
      frameworks and networks is an emerging and rapidly developing field of research.
      Self-assembling organic-inorganic compounds offer immense potential for
      functionalising material properties for a wide scope of applications including
      solar cells, light emitters, gas sensors and bipolar transparent conductors. The
      flexibility of combining two distinct material classes into a single solid-state
      system provides an almost infinite number of chemical and structural
      possibilities; however, there is currently no systematic approach established for
      designing new compositions and configurations with targeted electronic or optical
      properties. We review the current status in the field, in particular, the range
      of hybrid systems reported to date and the important role of materials modelling
      in the field. From theoretical arguments, the Mott insulator-to-metal transition
      should be possible in semiconducting metal-organic frameworks, but has yet to be
      observed. The question remains as to whether electro-active hybrid materials will
      evolve from chemical curiosities towards practical applications in the near term.

PMID- 22858740
TI  - Emergency Severity Index version 4: a valid and reliable tool in pediatric
      emergency department triage.
AB  - OBJECTIVES: The Emergency Severity Index version 4 (ESI v.4) is the most recently
      implemented 5-level triage system. The validity and reliability of this triage
      tool in the pediatric population have not been extensively established. The goals
      of this study were to assess the validity of ESI v.4 in predicting hospital
      admission, emergency department (ED) length of stay (LOS), and number of
      resources utilized, as well as its reliability in a prospective cohort of
      pediatric patients. METHODS: The first arm of the study was a retrospective chart
      review of 780 pediatric patients presenting to a pediatric ED to determine the
      validity of ESI v.4. Abstracted data included acuity level assigned by the triage
      nurse using ESI v.4 algorithm, disposition (admission vs discharge), LOS, and
      number of resources utilized in the ED. To analyze the validity of ESI v.4,
      patients were divided into 2 groups for comparison: higher-acuity patients (ESI
      levels 1, 2, and 3) and lower-acuity patients (ESI levels 4 and 5). Pearson chi
      analysis was performed for categorical variables. For continuous variables, we
      conducted a comparison of means based on parametric distribution of variables.
      The second arm was a prospective cohort study to determine the interrater
      reliability of ESI v.4 among and between pediatric triage (PT) nurses and
      pediatric emergency medicine (PEM) physicians. Three raters (2 PT nurses and 1
      PEM physician) independently assigned triage scores to 100 patients; k and
      interclass correlation coefficient were calculated among PT nurses and between
      the primary PT nurses and physicians. RESULTS: In the validity arm, the
      distribution of ESI score levels among the 780 cases are as follows: ESI 1: 2
      (0.25%); ESI 2: 73 (9.4%); ESI 3: 289 (37%); ESI 4: 251 (32%); and ESI 5: 165
      (21%). Hospital admission rates by ESI level were 1: 100%, 2: 42%, 3: 14.9%, 4:
      1.2%, and 5: 0.6%. The admission rate of the higher-acuity group (76/364, 21%)
      was significantly greater than the lower-acuity group (4/415, 0.96%), P < 0.001.
      The mean ED LOS (in minutes) for the higher-acuity group was 257 (SD, 132) versus
      143 (SD, 81) in the lower-acuity group, P < 0.001. The higher-acuity group also
      had significantly greater use of resources than the lower-acuity group, P <
      0.001. The percentage of low-acuity patients receiving no resources was 54%,
      compared with only 26% in the higher-acuity group. Conversely, a greater
      percentage of higher-acuity patients utilized 2 or more resources than the lower
      acuity cohorts, 43% vs 12%, respectively, P < 0.001. In the prospective
      reliability arm of the study, 15 PT nurses and 8 PEM attending physicians
      participated in the study; k among nurses was 0.92 and between the primary triage
      nurses and physicians was 0.78, P < 0.001. The intraclass correlation coefficient
      was 0.96 for PT nurses and 0.91 between the primary triage nurse and physicians,
      P < 0.001. CONCLUSIONS: Emergency Severity Index v.4 is a valid predictor of
      hospital admission, ED LOS, and resource utilization in the pediatric ED
      population. It is a reliable pediatric triage instrument with high agreement
      among PT nurses and between PT nurses and PEM physicians.

PMID- 22858741
TI  - Assessment of factors associated with the delayed transfer of pediatric trauma
      patients: an emergency physician survey.
AB  - OBJECTIVES: The purpose of this study was to identify, among emergency department
      (ED) physicians, the potential barriers impacting the appropriate and timely
      transfer of injured children to pediatric trauma centers. METHODS: Surveys
      assessed pediatric trauma knowledge and experience, transfer and imaging
      decisions, and perceived barriers to patient transfer. Two scenarios were
      created; one with a child meeting the state trauma triage criteria and one who
      did not. In April 2010, 936 surveys were mailed to randomly selected ED
      physicians. Respondents could answer by mail or online until June 30, 2010.
      RESULTS: A total of 486 surveys were returned, and 109 were excluded, leaving 377
      included in the study. A majority reported limited experience in the care of the
      critically ill child, with 93%, 99%, 99%, and 100% respectively, having performed
      less than 5 intubations, intraosseous line, central line, or chest tube
      placements in the last year. In the scenario in which the child met criteria to
      be transferred, 74% appropriately transferred the patient, whereas in the other
      scenario, 34% transferred the patient. As much as 56% of the respondents reported
      they would perform a head computed tomography before transfer, mainly to avoid
      missed injuries and medicolegal concerns. Among those who would not transfer
      either patient, 27% reported not having an on-call surgeon at all times.
      CONCLUSIONS: Innovative measures should be developed so that ED physicians gain a
      greater understanding of the proper identification of pediatric patients
      requiring a timely transfer to a pediatric trauma center.

PMID- 22858742
TI  - Children will eat the strangest things: a 10-year retrospective analysis of
      foreign body and caustic ingestions from a single academic center.
AB  - BACKGROUND: Foreign body (FB) ingestions are common in children presenting to the
      emergency department. Health care providers are quickly challenged to determine
      which children need urgent endoscopy for diagnostic or therapeutic reasons. We
      performed a retrospective study to determine if esophageal injury caused by FB
      ingestion correlated to presenting signs or symptoms, location of impaction,
      duration of impaction, or denomination of coin (as this was the most commonly
      ingested FB). METHODS: A retrospective chart review of children between birth and
      17 years of age who presented for esophagogastroduodenoscopy for removal of upper
      gastrointestinal FB was performed. Demographic data collected from all children
      included age, sex, and race. For children with FB ingestion, the type of FB,
      location of the FB, underlying gastrointestinal pathology, duration of impaction,
      and endoscopic findings were recorded. Descriptive analysis of the data was
      performed using means, medians, SD, and percentages; chi test was used to test
      the association between categorical variables. RESULTS: Over a 10-year period of
      review, a total of 3279 esophagogastroduodenoscopies were performed; 248 (7.8%)
      were done for FB removal. The mean age for children having endoscopy for FB
      removal was 3.9 (SD, 3.2) years (median, 3.1 years); there was a slight male
      predominance (male/female ratio = 1.6:1). The vast majority (81%) of retained FBs
      was coins. Most of the FBs were located in the upper esophagus (68%). Success
      rate for retrieval was greater for esophageal FBs (99%) than for more distally
      located FBs (70%; P < 0.001). Mucosal ulceration, seen in 59 children (30%), was
      related to a complaint of substernal pain but not vomiting, respiratory distress,
      or drooling. The finding of esophageal ulceration was not related to location of
      coin impaction or denomination of ingested coin but was related to duration of
      impaction and the unexpected finding of FB during chest radiograph. Underlying
      pathology was found more commonly in children with meat bolus impaction (100%)
      than in children with other FB ingestions (3.6%; P < 0.001). CONCLUSIONS:
      Ingestion of FBs by children remains a significant problem faced by emergency
      department personnel. In our study, a complaint of substernal chest pain in
      children with an esophageal FB predicted esophageal ulceration. Also, esophageal
      FBs unexpectedly found on chest radiograph or known to be present greater than 72
      hours were more likely to have esophageal ulceration. These clinical and historic
      clues can help direct appropriate prompt referral for endoscopic removal.

PMID- 22858743
TI  - No longer a "nursemaid's" elbow: mechanisms, caregivers, and prevention.
AB  - OBJECTIVES: We sought to identify specific mechanisms leading to radial head
      subluxation, as well as correlation with different caregivers, as a potential
      platform for education and injury prevention. METHODS: A retrospective cohort
      study of all patients admitted to an urban pediatric tertiary care emergency
      department with radial head subluxation from 1995 to 2009 was performed. Cases
      were identified using a text-search module followed by a manual chart review. We
      excluded patients with fractures, osteopenia, and neuromuscular conditions. Data
      collected included age, gender, arm involved, position of the arm at
      presentation, mechanism of injury, caregivers involved, imaging, and type of
      reduction. Multivariate logistic regression analysis was used to determine
      predictors for different mechanisms. RESULTS: There were 3170 cases of radial
      head subluxation identified. The median age was 2.1 years (interquartile range,
      1.5-2.8 years), and 59% were female (95% confidence interval [CI], 57%-60%).
      There were 2011 patients (63%) presenting with a traction mechanism, 547 (17%)
      with a nontraction traumatic mechanism, and 612 (19%) with an unknown or
      undocumented mechanism.Within the traction group, we identified several
      potentially preventable mechanisms including lifting the child by the arms
      (28.3%), "wrestling" (12.3%), swinging child by the arms (9.2%), and placing the
      child into and out of a seat (4.3%). Male caregivers were more likely to be
      involved when a child is swung by the arms (odds ratio [OR], 3.2; 95% CI, 1.6
      6.2), lifted (OR, 1.9; 95% CI, 1.4-2.7), or "wrestled" with (OR, 6.4; 95% CI, 3.3
      12.0). Mechanisms common for female caregivers included the child pulling away
      from parent (OR, 2.3; CI, 1.54 3.4), tripping (2.0; CI, 1.3-3.0), and getting
      dressed (OR, 2.1; CI, 1.1-4.4). CONCLUSIONS: Radial head subluxation mechanisms
      can be classified into subcategories, which may be caregiver and even patient
      gender specific. Provider awareness regarding these mechanisms may help target
      education and prevention.

PMID- 22858744
TI  - Functional outcome after air-stirrup ankle brace or fiberglass backslab for
      pediatric low-risk ankle fractures: a randomized observer-blinded controlled
      trial.
AB  - OBJECTIVES: Pediatric ankle fractures are usually treated by immobilization with
      either a posterior splint, cast, or ankle brace. We set out to determine if the
      below-knee fiberglass posterior splint was as effective as the Air-Stirrup ankle
      brace in returning children with a low risk ankle fracture to their normal level
      of activity. METHODS: This was a randomized, single-blinded, noninferiority,
      controlled trial at the Royal Children's Hospital, Melbourne. Children aged 5 to
      15 years presenting acutely with a low-risk ankle fracture were randomized to the
      Air-Stirrup ankle brace or fiberglass posterior splint. A validated self-reported
      outcome tool, the Activities Scale for Kids performance (ASKp), was used to
      measure physical functioning over the 4 week period. Main outcome was ASKp scores
      at 2 and 4 weeks with secondary outcomes including pain, weight-bearing ability,
      and acceptability of device. RESULTS: Forty-five patients were randomized: 23 in
      the posterior splint group and 22 in the Air-Stirrup ankle brace. Study groups
      were similar in terms of age, fracture type, and baseline pain. More of the
      posterior splint group were non-weight bearing "at enrollment" (96%) compared
      with the ankle brace group (77%). The median ASKp score at 4 weeks was 91.9 in
      the brace group and 84.2 in the posterior splint group. Scores on the ASKp as
      well as ASKp differences were favorable toward the brace in the 11- to 15-year
      age group at 2 weeks (69.6 vs 55.6) and 4 weeks (97.5 vs 90.2) but trended toward
      the posterior splint in the 5- to 10-year age group (47.5 vs 56). CONCLUSIONS:
      There was no difference between the Air-Stirrup ankle brace and the fiberglass
      posterior splint in returning children to their normal levels of activity.

PMID- 22858745
TI  - Intranasal ketamine for procedural sedation in pediatric laceration repair: a
      preliminary report.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of 3 doses of
      intranasal ketamine (INK) for sedation of children from 1 to 7 years old
      requiring laceration repair. METHODS: This was a randomized, prospective, double
      blind trial of children requiring sedation for laceration repair. Patients with
      simple lacerations were randomized by age to receive 3, 6, or 9 mg/kg INK.
      Adequacy and efficacy of sedation were measured with the Ramsay sedation score
      and the Observational Scale of Behavioral Distress-Revised. Serum ketamine and
      norketamine levels were drawn during the procedure. Sedation duration and adverse
      events were recorded. RESULTS: Of the 12 patients enrolled, 3 patients achieved
      adequate sedation, all at the 9-mg/kg dose. The study was suspended at that time
      as per predetermined criteria. CONCLUSIONS: Nine milligrams of INK per kilogram
      produced a significantly higher proportion of successful sedations than the 3-
      and 6-mg/kg doses.

PMID- 22858746
TI  - All-terrain vehicle dealership point-of-sale child safety compliance in Illinois.
AB  - OBJECTIVES: In 2008, an estimated 37,700 children younger than 16 were treated in
      US emergency departments for nonfatal all-terrain vehicle (ATV) injuries. This
      study identifies safety guidelines and recommendations dealers convey to
      consumers at the point of sale. METHODS: A telephone survey of all 2004 licensed
      motorcycle dealers in Illinois was conducted. Trained investigators, using
      aliases and posing as a parent of a 13-year-old teenager, spoke with dealership
      personnel. Investigators indicated they wished to purchase an ATV with the
      dealership, but had no knowledge of ATV use or safety issues. The telephone
      call's true purpose was concealed during the survey. Specific responses from the
      salesperson, models and brands of ATVs, price quotes, engine sizes, and safety
      information/recommendations were recorded in a written survey instrument.
      RESULTS: One hundred twenty-seven ATV dealers completed the survey. A salesperson
      most often fielded the telephone interview (124/127). Telephone interviews by
      male investigators were longer than those by female interviewers (5 minutes 37
      seconds vs 3 minutes 51 seconds; P = 0.001). Dealers recommended Consumer Product
      Safety Commission-based child-size ATVs (<90 mL engine size) during 75% of the
      calls. Nearly all dealers recommended helmet use (108/127), and few (3/127)
      labeled the vehicles as "safe." Most dealers (83.5%) recommended some form of
      rider training, with half (49.6%) offered point-of-purchase training.
      CONCLUSIONS: All-terrain vehicle dealers in Illinois recommend child-size
      vehicles, safety training, and helmet use for the majority of telephone
      inquiries. Injury prevention efforts targeting ATV dealers may be less needed
      than those using other populations.

PMID- 22858747
TI  - B-type natriuretic peptide in the recognition of critical congenital heart
      disease in the newborn infant.
AB  - OBJECTIVE: Infants with congenital heart disease having obstruction to the left
      ventricular outflow and ductal-dependent systemic circulation can present
      critically ill with shock. Prompt disease recognition and initiation of
      prostaglandins are necessary to prevent excess morbidity and mortality. We
      assessed a large cohort of newborn infants with ductal-dependent systemic
      circulation to determine if B-type natriuretic peptide (BNP) is consistently
      elevated at presentation, potentially aiding in diagnosis and treatment. METHODS:
      The clinical records of infants with left-sided obstructive lesions admitted from
      January 2005 to June 2009 were reviewed. Infants were divided into 2 groups:
      group 1 was diagnosed with cardiogenic/circulatory shock at presentation, and
      group 2 consisted of infants with ductal-dependent systemic circulation without
      evidence of shock. B-type natriuretic peptide levels and other variables between
      the groups were compared. RESULTS: All patients with critical congenital heart
      disease presenting with shock had elevated BNP levels, ranging from 553 to
      greater than 5000 pg/mL. Infants in group 1 (shock, n = 36) had significantly
      higher median BNP levels of 4100 pg/mL at presentation compared with group 2
      patients (no shock, n = 86), who had a median BNP of 656 pg/mL (range, 30-3930
      pg/mL; P < 0.001). Every 100 U of increase in BNP at presentation increased the
      likelihood of shock (odds ratio, 100; P < 0.001). CONCLUSIONS: B-type natriuretic
      peptide is markedly elevated in neonates presenting in shock secondary to left
      sided obstructive heart disease and is an important diagnostic tool to aid in the
      rapid identification and treatment of these patients.

PMID- 22858748
TI  - Comparison of direct laryngoscopy to Pediatric King LT-D in simulated airways.
AB  - OBJECTIVES: Previous reports have shown a high rate of ventilation failure via
      direct laryngoscopy as compared with the King LT-D airway. This difference is
      further divergent in the pediatric population. The goal of this study was to
      compare the difference in efficacy of ventilation by prehospital providers in a
      simulated environment between direct laryngoscopy and Pedi-King LT-D. METHODS: In
      this study, 37 paramedics were exposed to 2 identical 5-minute clinical scenarios
      in a simulation center using a pediatric simulation tool. In the first scenario,
      the provider was given all of the standard laryngoscopy equipment. In the second
      scenario, they were given access only to the Pedi-King LT-D. A comparison of
      adequate ventilation time between the scenarios was performed. RESULTS: A mean
      improvement of 102 seconds was found when using the Pedi-King airway, with a
      clinically significant P < 0.0001. CONCLUSIONS: With a significant improvement in
      ventilation time in these simulated airways, consideration should be made to
      practice placement of the King Airway Device as first-line airway stabilization.
      Further live prospective studies would aid in this recommendation.

PMID- 22858749
TI  - Radiologic predictors of hyponatremia in children hospitalized with community
      acquired pneumonia.
AB  - BACKGROUND: Hyponatremia (HNa) is the most common electrolyte imbalance seen in
      clinical practice and a common laboratory finding in children with community
      acquired pneumonia (CAP). This study investigated whether there is a link between
      the radiological pattern seen in patients with CAP and the occurrence of HNa,
      hypothesizing that children with moderate and severe HNa would have a lobar
      segmental pattern on chest radiograph. METHODS: The medical files and chest
      radiographs of 54 children with moderate to severe HNa (sodium <130 mmol/L)
      admitted with CAP over a 2-year period at our institution were retrospectively
      studied. Community-acquired pneumonia was defined as either lobar-segmental or
      interstitial by a radiologist blinded to laboratory results. RESULTS:
      Hyponatremia was seen more frequently in children with lobar-segmental pneumonia:
      40 (74%) compared with 14 (26%) with interstitial pneumonia (P = 0.004). There
      was no relationship between the pattern of pneumonia seen on chest radiograph and
      severity of HNa; however, all 6 cases of severe HNa had lobar-segmental CAP, and
      all patients with complicated CAP were from the lobar-segmental group.
      CONCLUSIONS: We found an association between lobar-segmental CAP and moderate or
      severe HNa. In addition, all cases of severe HNa occurred in patients with lobar
      segmental CAP. The presence of a lobar-segmental pattern on chest radiography in
      CAP suggests the need for assessment of electrolyte status even in patients with
      adequate respiratory status.

PMID- 22858750
TI  - The role of physician assistants in a pediatric emergency department: a center
      review and survey.
AB  - OBJECTIVES: The objectives of this study were to outline the clinical conditions
      presenting to a Canadian pediatric emergency department (ED), survey the opinions
      of physician assistants (PAs) and emergency pediatricians to determine which
      conditions they consider could be managed by PAs, and to estimate the proportion
      of the total pediatric ED volume that PAs could potentially manage. METHODS: We
      reviewed the 2007 British Columbia Children's Hospital database of ED visits to
      identify clinical presentation and chief complaint of all patients seen.
      International Classification of Diseases, 10th Revision codes were used to
      categorize the presenting complaint of each ED visit. Following categorization,
      the results were discussed by a focus group composed of pediatric emergency
      medicine-trained physicians and PAs, to review the list of chief complaints. We
      then surveyed via e-mailed questionnaire a group of emergency pediatricians (n =
      17) and PAs (n = 5) to seek their opinion on the categories of clinical
      presentation appropriate for PA management. RESULTS: Of 38,722 visits, 9.2% were
      triaged as "resuscitation" or "emergent." We sorted the remaining 35,077 ED
      visits into 57 clinical categories. More than 85% of respondents selected 30
      clinical categories for PA management with physician supervision, representing
      74% of the total ED volume. Of these, 3 were also deemed appropriate for PA
      management without direct physician supervision. There were statistically
      significant differences in mean length of stay, waiting time, and admission rates
      between the clinical conditions selected for PA involvement. However, the
      difference in waiting time was not clinically meaningful. CONCLUSIONS: A large
      proportion of pediatric ED visits are designated as semiurgent or nonurgent.
      Clinicians (ED physicians and PAs) thought that the majority of these ED visits
      could be managed by PAs.

PMID- 22858751
TI  - Accuracy of ultrasonography versus computed tomography scan in detecting
      parapharyngeal abscess in children.
AB  - OBJECTIVE: Significant morbidity and rarely mortality have been described in
      parapharyngeal space infections in children; hence, the decision on the timing of
      surgical intervention might be crucial. The aim of this study was to compare the
      accuracy of plain x-rays, ultrasonography (US), and contrast-enhanced computed
      tomography (CT) in demonstrating a parapharyngeal abscess. METHODS: A
      retrospective study on all patients with parapharyngeal abscess admitted and
      operated on from January 1996 to December 2000 was carried out. Charts were
      reviewed for patients' demographics, symptoms and signs, details of workup,
      intraoperative findings, and culture results. The CT scans were reviewed for the
      presence of a rim enhancement, a presence of a definable wall, and fluid-fluid
      level and were correlated with the plain x-rays and US results and intraoperative
      findings. RESULTS: Eighteen patients with proven parapharyngeal infection were
      included: 10 with proven abscess and 8 with cellulitis. The sensitivity and
      specificity of lateral neck radiograph and US were low compared with a
      specificity of 87.5 while evaluating fluid-fluid level seen on the CT scan,
      sensitivity of 58.3% for the presence of a definable abscess wall, and a
      sensitivity of 100% for the presence of a prominent wall. CONCLUSIONS: Our study
      demonstrates good rates of accuracy of CT scan for diagnosing a parapharyngeal
      abscess. Our study suggest that it is appropriate to obtain a CT scan upon
      presentation in all children with suspected parapharyngeal abscess and that a CT
      scan is proven to be a useful diagnostic tool in establishing a treatment plan.

PMID- 22858752
TI  - Attitudes and knowledge regarding emergency contraception among emergency
      department adolescents and providers.
AB  - OBJECTIVE: Teen pregnancy is a public health issue in the United States.
      Emergency contraception (EC) has the potential to reduce teen pregnancy rates.
      The use of EC remains controversial, and barriers have been identified for
      adolescents seeking care. The objective of this study was to evaluate
      similarities and differences of knowledge and attitudes regarding EC among
      pediatric emergency department (PED) female adolescents, nurses, and
      physicians/nurse practitioners (NPs). METHODS: A quantitative survey including
      demographics, knowledge, and attitudes regarding EC was administered to 3 groups:
      (1) PED nurses, (2) PED physicians and NPs, and (3) adolescent female patients
      seeking care in the PED. Demographic data were analyzed using descriptive
      statistics. Differences between groups were analyzed using Student t test for
      continuous variables and chi or Fisher exact test for categorical variables.
      Attitude and knowledge differences among the groups were analyzed using the
      nonparametric Wilcoxon test. RESULTS: There was no difference in overall
      knowledge regarding EC between nurses and physicians/NPs, adolescents and nurses
      or adolescents and physicians/NPs, and overall knowledge was poor among all
      groups. There was no difference in overall attitudes between nurses and
      adolescents; however, physicians were more liberal in their attitudes regarding
      EC compared with adolescents (P < 0.0001) and nurses (P < 0.0001). Older age
      trended toward more conservative responses (P = 0.05). CONCLUSIONS: Adolescents
      and nurses had more conservative attitudes toward EC than physicians. Further
      studies are needed to confirm the generalizability of these findings.

PMID- 22858753
TI  - Yield of diagnostic studies in children presenting with complex febrile seizures.
AB  - OBJECTIVE: The objective of this study was to determine the yield of diagnostic
      workup in children presenting with complex febrile seizures. METHODS: We
      performed a retrospective review of charts of patients who presented to our
      pediatric emergency department with complex febrile seizures (focal, prolonged,
      or recurrent). Patients with known seizure disorder, congenital central nervous
      system malformations, or hydrocephalus were excluded. The charts were reviewed
      for diagnostic workup. RESULTS: There were 71 eligible encounters (mean age, 1.5
      years); 59.2% were males. None of the 71 patients had positive blood or urine
      cultures; none had abnormal blood count or serum chemistries. Only 1 patient who
      had a very abnormal presentation in febrile status epilepticus had positive
      cerebrospinal fluid culture and abnormal brain computed tomography scan and
      magnetic resonance imaging. CONCLUSIONS: Most patients with complex febrile
      seizures do not require extensive diagnostic workup.

PMID- 22858754
TI  - Antibiotic administration can be an independent risk factor for therapeutic delay
      of pediatric acute appendicitis.
AB  - OBJECTIVES: Little is known about the relationship between prior treatment with
      antibiotics and delay of diagnosis and treatment in pediatric acute appendicitis
      (AA). We have defined a situation requiring more than 48 hours from the onset of
      symptoms to surgery in pediatric AA as "therapeutic delay." The aim of this study
      was to investigate the risk factors contributing to therapeutic delay in
      pediatric AA. METHODS: We conducted a retrospective chart review of AA children
      operated on between 2003 and 2008 at tertiary-care pediatric and perinatal
      hospitals. Univariate and multivariate logistic regressions were analyzed to
      determine independent risk factors of therapeutic delay in pediatric AA. RESULTS:
      The duration between the onset of symptoms and surgery was more than 48 hours
      (therapeutic delay) in 50 patients (25%, group A) and 48 hours or less in 151
      patients (75%, group B). The patients in group A had a significantly higher
      frequency of diarrhea (48% vs 12%; P < 0.0001). The percentages of children who
      had previously received antibiotics were more frequent in group A (46% vs 8%; P <
      0.0001). The median C-reactive protein levels (72 vs 7 mg/L; P < 0.0001) and
      frequency of perforation (60% vs 13%; P < 0.0001) were statistically
      significantly higher in group A. A multivariate analysis demonstrated that the
      independent risk factors of therapeutic delay were history of receiving
      antibiotics (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.3-15.5),
      diarrhea (OR, 5.2; 95% CI, 2.1-13.1), and elevated C-reactive protein levels (OR,
      4.5; 95% CI, 1.9-10.8). CONCLUSIONS: Prior treatment with antibiotics was an
      independent risk factor for therapeutic delay in pediatric AA.

PMID- 22858755
TI  - Postdischarge adverse events related to sedation for diagnostic imaging in
      children.
AB  - OBJECTIVES: The objectives of this study were to describe the type and frequency
      of postdischarge adverse events related to sedation for elective diagnostic
      imaging in children and to determine if any patient or drug characteristics were
      associated with such adverse events. METHODS: We conducted a prospective
      observational study of children younger than 18 years who underwent sedation for
      elective magnetic resonance imaging at a tertiary care hospital. We administered
      a postdischarge adverse event questionnaire to families within 3 to 5 days after
      sedation to assess adverse events such as behavioral changes, vomiting, recovery
      time to baseline status, and need for medical follow-up. RESULTS: We enrolled 322
      patients, of which 253 (78.5%) completed phone follow-up. The majority of study
      patients were male (58.1%) and belonged to American Society of Anesthesiologists
      category 2 (52.2%). A combination of pentobarbital and midazolam (53.4%) was the
      most commonly used sedation medication; 64.4% patients experienced postdischarge
      adverse events. The most common postdischarge adverse event reported were
      incoordination of movements (53.8%), dizziness (31.2%), and agitation (19.8%);
      48.6% of patients required more than 9 hours to return to baseline behavior. No
      patient required evaluation at a medical facility for these postdischarge adverse
      events. Logistic regression analysis showed that use of pentobarbital and adverse
      event during sedation were significantly associated with postdischarge adverse
      events. CONCLUSIONS: Postdischarge adverse events related to sedation for
      diagnostic imaging are minor, mostly behavioral, but occur in a significant
      number of patients. Parents should be provided with detailed discharge
      instructions to anticipate such adverse events at home.

PMID- 22858757
TI  - Synthesis, assembly and reaction of a nanocatalyst in microfluidic systems: a
      general platform.
AB  - We present a successive microfluidic approach to create and characterize
      hierarchical catalyst structures consisting of metal-decorated nanoparticles that
      are assembled into porous microparticles ("supraball" catalysts). First, using a
      silicon microreactor, platinum nanoparticles with a very narrow size distribution
      are grown and immobilized uniformly onto iron oxide/silica core-shell
      nanospheres. The Pt-decorated silica nanospheres are then assembled into uniform,
      spherical, micron-sized particles by using emulsion templates generated with a
      microfluidic drop generator. Finally, the assembled supraballs are loaded into a
      packed-bed microreactor for characterization of the catalytic reactivity. The
      prepared material showed excellent catalytic activity for the oxidation of
      aldehyde with only ~1 mg of material (containing ~50 MUg of platinum
      nanoparticles). After the reactions, all the supraball catalysts are recovered by
      using the magnetic property of the underlying iron oxide/silica core-shell
      nanospheres.

PMID- 22858756
TI  - Stable isotope gas chromatography-tandem mass spectrometry determination of
      aminoethylcysteine ketimine decarboxylated dimer in biological samples.
AB  - Aminoethylcysteine ketimine decarboxylated dimer (AECK-DD; systematic name: 1,2
      3,4-5,6-7,8-octahydro-1,8a-diaza-4,6-dithiafluoren-9(8aH)-one) is a previously
      described metabolite of cysteamine that has been reported to be present in
      mammalian brain, urine, plasma, and cells in culture and vegetables and to
      possess potent antioxidative properties. Here, we describe a stable isotope gas
      chromatography-tandem mass spectrometry (GC-MS/MS) method for specific and
      sensitive determination of AECK-DD in biological samples. (13)C(2)-labeled AECK
      DD was synthesized and used as the internal standard. Derivatization was carried
      out by N-pentafluorobenzylation with pentafluorobenzyl bromide in acetonitrile.
      Quantification was performed by selected reaction monitoring of the mass
      transitions m/z 328 to 268 for AECK-DD and m/z 330 to 270 for [(13)C(2)]AECK-DD
      in the electron capture negative ion chemical ionization mode. The procedure was
      systematically validated for human plasma and urine samples. AECK-DD was not
      detectable in human plasma above approximately 4nM but was present in urine
      samples of healthy humans at a maximal concentration of 46nM. AECK-DD was
      detectable in rat brain at very low levels of approximately 8pmol/g wet weight.
      Higher levels of AECK-DD were detected in mouse brain (~1nmol/g wet weight).
      Among nine dietary vegetables evaluated, only shallots were found to contain
      trace amounts of AECK-DD (~6.8pmol/g fresh tissue).

PMID- 22858758
TI  - Evaluating the enthalpic contribution to ligand binding using QM calculations:
      effect of methodology on geometries and interaction energies.
AB  - As a result of research on ligand efficiency in the pharmaceutical industry,
      there is greater focus on optimizing the strength of polar interactions within
      receptors, so that the contribution of overall size and lipophilicity to binding
      can be decreased. A number of quantum mechanical (QM) methods involving simple
      probes are available to assess the H-bonding potential of different heterocycles
      or functional groups. However, in most receptors, multiple features are present,
      and these have distinct directionality, meaning very minimalist models may not be
      so ideal to describe the interactions. We describe how the use of gas phase QM
      models of kinase protein-ligand complex, which can more closely mimic the polar
      features of the active site region, can prove useful in assessing alterations to
      a core template, or different substituents. We investigate some practical issues
      surrounding the use of QM cluster models in structure based design (SBD). These
      include the choice of the method; semi-empirical, density functional theory or ab
      initio, the choice of the basis set, whether to include implicit or explicit
      solvation, whether BSSE should be included, etc. We find a combination of the M06
      2X method and the 6-31G* basis set is sufficiently rapid, and accurate, for the
      computation of structural and energetic parameters for this system.

PMID- 22858759
TI  - Cell migration: (en)ABLing T cell migration.

PMID- 22858761
TI  - [Occupational health: history and future challenges].

PMID- 22858760
TI  - Development, characterization and efficacy of niosomal diallyl disulfide in
      treatment of disseminated murine candidiasis.
AB  - In the current study, a novel niosome based formulation of diallyl disulfide
      (DADS) was evaluated for its potential to treat disseminated candidiasis in mouse
      model. Among various non-ionic surfactants tested, niosome formulation prepared
      using Span 80 was found to be most efficient in the entrapment of DADS. The DADS
      loaded niosomes had size dimensions in the range of 140 +/- 30 nm with zeta
      potential of -30.67 +/- 4.5. Liver/kidney function tests as well as
      histopathologic studies suggested that noisome-based DADS formulations are safe
      at the dose investigated. When administered to Candida albicans infected animals,
      the DADS bearing niosomal formulation cleared the fungal burden and increased
      their survival much efficiently than its free form. FROM THE CLINICAL EDITOR: In
      this study, a novel niosomal formulation of the antifungal DADS was utilized in a
      murine candidiasis model, resulting in more efficient fungal clearance compared
      to the free formulation.

PMID- 22858762
TI  - [Tuberculosis among healthcare workers and health students: an outstanding issue
      for healthcare services and the university].

PMID- 22858763
TI  - [Blood disorders among workers exposed to a mixture of benzene-toluene-xylene
      (BTX) in a paint factory].
AB  - OBJECTIVES: Evaluate the three blood cell series and identify the presence of
      hypochromia, macrocytosis, leucopenia, lymphopenia, and thrombocytopenia in a
      group of workers exposed to the mixture of benzene-toluene-xylene (BTX).
      MATERIALS AND METHODS: A cross-sectional study which included 97 workers from a
      paint factory in Mexico. The participants underwent conventional blood count and
      tests for potential cumulative daily dose of BTX fumes, to estimate exposure.
      RESULTS: From the total of workers, 19.6% showed macrocytosis, 18.6%,
      lymphopenia, hypochromia 10.3%, 7.2% and 5.2% thrombocytopenia leukopenia. The
      crude association of macrocytosis with exposure to high doses of BTX mixture was
      the only with statistical significance (OR: 3.6, 95% CI 1.08 to 13.9, P = 0.02),
      and the base for a logistic regression model (OR: 6.7, 95% CI 1.33 to 13.55, P =
      0.02) adjusted for age, alcohol consumption, and smoking. CONCLUSIONS: All blood
      cytological components analyzed demonstrated mild changes, potentially associated
      with exposure to the mixture of BTX. Macrocytosis could constitute an early
      manifestation worthy for surveillance.

PMID- 22858764
TI  - [Evaluation of physical fitness levels in children and adolescents: establishing
      percentile charts for the central region of Peru].
AB  - OBJECTIVES: Construct percentile charts and physical fitness (PF) reference
      values stratified by age and sex of children and adolescents from Peru's central
      region. MATERIALS AND METHODS: The sample was comprised of 7,843 subjects (4,155
      females and 3,688 males) between the ages of 6 to 17 years old. Physical fitness
      was assessed using six tests developed by EUROFIT, FITNESSGRAM and AAPHERD.
      Percentile charts were developed separately for males and females using the LMS
      method calculated with LMSchartmaker software. Results. Males showed higher PF
      values with the exception of flexibility; a clear increase in PF with increasing
      age was verified. CONCLUSIONS: Inter-individual variability in both sexes is
      substantial. Charts and specific reference values by age and sex may be used for
      the assessment and interpretation of children's and adolescents' PF levels in
      Peru's central region. These findings may be of help to educators, public health
      professionals, parents, and policy-makers when assessing schools' physical
      education programs.

PMID- 22858765
TI  - [Variation of the enzymatic activity of Bothrops atrox "jergon" snake venom from
      three geographic regions, Peru].
AB  - OBJECTIVES: To study the variability in the composition and enzymatic activity of
      venom from adult Bothrops atrox specimens. MATERIALS AND METHODS: We used venoms
      from adult snakes from Amazonas, Junin and Ucayali. Each of the venom samples
      underwent analysis for protein and number of bands by pagesds. Phospholipase A2,
      hemolytic, amidolytic, coagulant, hemorrhagic activity were analyzed, also and
      proteolytic activity on casein and by zymogram. Additionally, immunodiffusion and
      neutralization assays in vitro were done with a polyvalent botropic serum from
      the national institute of health of Peru. RESULTS: The amidolytic, coagulant,
      hemorrhagic, proteolytic by zymogram, phospholipase A2, and indirect hemolytic
      activity were variable, demonstrating increased activity in the venoms from
      Amazonas, regarding proteolytic by zymogram, phospholipase A2, and indirect
      hemolytic activity. While the amount of protein electrophoretic bands and
      proteolytic activity on casein did not demonstrated differences. Regarding
      neutralization tests, a 0.5 dose of antivenom was sufficient to effectively
      neutralize (>50%) the coagulant activity and phospholipase A2 of all samples
      analyzed. CONCLUSIONS: Some biological properties of the venom from adult
      Bothrops atrox of Peru are variable, without interference with the in vitro
      neutralization by the polyvalent botropic serum on coagulant and phospholipase A2
      properties of the venom.

PMID- 22858766
TI  - [The frequency and antibiotic susceptibility of Staphylococcus aureus from nasal
      swabs in an suburban marginal population in Lima, Peru].
AB  - OBJECTIVES: To determine the frequency and associated factors of nasal
      colonization by Staphylococcus aureus and its antibiotic susceptibility pattern
      in a marginal suburban population Lima, Peru. MATERIALS AND METHODS: A cross
      sectional study was conducted among population of all ages from a marginal
      suburban district in northern Lima. The study used a convenience sample. Each
      person was surveyed and provided a swab sample of the nostrils. The swab samples
      were analyzed to identify Staphylococcus aureus, determining the susceptibility
      pattern by the Kirby Bauer disk diffusion method. RESULTS: From the 452
      participants recruited, ages between 1 and 84 years, the frequency of
      Staphylococcus aureus nasal colonization was 24.6%, with 0.9% of them resistant
      to methicillin. The only factor associated with nasal colonization was age equal
      or less than 11 years (OR: 3.80, 95% CI 1.42 to 10.16). Most strains were
      resistant to penicillin (96.4%) but also to erythromycin (10.9%), clindamycin
      (7.3%) and gentamicin (4.5%). CONCLUSIONS: The frequency of Staphylococcus aureus
      nasal colonization was similar to other studies worldwide, with predominance of
      methicillin-sensitive strains.

PMID- 22858767
TI  - [Self-medication behavior among pregnant women user of the Instituto Nacional
      Materno Perinatal, Peru 2011].
AB  - We aim to determine the prevalence of self prescribing behaviour during pregnancy
      and its characteristics. For this purpose, we designed a cross sectional study
      and interviewed 400 pregnant women who had their prenatal care at Instituto
      Nacional Materno Perinatal, Lima. We found that 10.5% of the patients (42
      patients) had a self prescribing behavior during pregnancy, 64.5% think that self
      prescribing behavior can produce congenital malformations. The medications used
      were classified as type A and B according to the Food and Drug Administration
      (FDA). Paracetamol was used more frequently (47.6%) followed by amoxicillin
      (16.7%). All the women who self-prescribed have had this behavior before
      pregnancy. According to these results, we conclude there is a low prevalence of
      self-prescribing behavior during pregnancy compared to the international
      literature.

PMID- 22858768
TI  - [Knowledge of epidemiological risk indicators used in clinical trials among
      medical students in advanced years and medical residents].
AB  - A cross-sectional study evaluated 182 students in the last two years of medical
      school and 70 residents of a national hospital in Peru on the risk indicators
      used for reporting results in clinical trials. A questionnaire was used to assess
      the ability to recognize and calculate risk indicators most widely used in the
      epidemiological literature. From the participants, 19.4% did not recognize any of
      the indicators and 81.4% was not able to calculate them. The relative risk
      reduction was the most recognized indicator (55.2%), followed by the number
      needed to treat (51.6%), the absolute risk reduction (26.6%), and the hazard
      ratio (9.5%). In conclusion, medical students in the last two years of school and
      medical residents do not recognize or are able to calculate properly the risk
      indicators used in clinical trials.

PMID- 22858769
TI  - [Tuberculosis detection in the emergency room: utility of same day smears].
AB  - Conducting a same day smears is a strategy that has recently been adopted by the
      World Health Organization. Our study sought to determine the additional
      diagnostic yield of a second sputum smear taken on the same day among patients
      with respiratory symptoms, attended at the emergency room from two hospitals in
      Lima. We included 270 patients from January to November 2011, which were asked
      two samples of sputum within two hours; the samples were processed by the Ziehl
      Neelsen method. The frequency of positive sputum smears was 18.5%. The additional
      diagnostic yield for the second smear was 20.9%. Considering the high prevalence
      of tuberculosis diagnosed by sputum smear, it is suggested that this test be
      included routinely in the emergency rooms of hospitals in Lima Metro area.

PMID- 22858770
TI  - [A decade of no effective inpatient medical discharges, experience from a
      hospital in Lima, Peru].
AB  - Our aim is to describe the financial implications of no effective in patient
      discharges from 2001-2010 from a general hospital in lima city. For this purpose
      we analyzed the total amounts, cancellations and exonarations from the patient
      accounts with a non effective medical discharge because of hospital "debts". We
      found that the number of patients with a non effective medical discharge
      decreased 70% from 2001 to 2010, the number of days between the medical discharge
      until the day the patient left the hospital decreased 80%. The total amounts,
      cancellations and exonarations decreased 63%, 53% and 68%, respectively. The
      average amount of exoneration was 61,7%. In conclusion, the non effective medical
      discharges increase patient debts, which are partially exonerated and assumed by
      the hospital. Even though it has decreased in the last decade, this could be
      explained by the implementation of the new health insurance policies.

PMID- 22858771
TI  - [Tuberculosis as occupational disease].
AB  - There is enough evidence to declare tuberculosis as an occupational disease among
      healthcare workers. In Peru, there are regulations granting employment rights
      regarding tuberculosis as an occupational disease, such as healthcare coverage
      for temporary or permanent disability. However, these rights have not been
      sufficiently socialized. This study presents information on the risk of acquiring
      tuberculosis in the workplace, and a review of the evidence to declare
      tuberculosis as an occupational disease among health care workers, presenting the
      current Peruvian law related.

PMID- 22858772
TI  - [Psychosocial risks at work and occupational health].
AB  - The changes on work processes and job design in recent decades are focused in the
      demographic, economic, political, and technological aspects. These changes have
      created new psychosocial risks at work that affect the health and quality of
      workplace, increasing stress levels among workers. The aim of this study is to
      present such risks, their consequences, and some recommendations to promote
      health at the workplace as a strategy to improve public health of the population.
      The study is divided into five points in which: (1) introduces the concept of
      risk factors and psychosocial work, (2) describes the main emerging psychosocial
      risks labor, (3) provides some information on the prevalence of psychosocial
      risks at work in Europe and its consequences, (4) recommendations for health
      promotion in the workplace, and (5) describes the objective of Occupational
      Health Psychology and concludes with the recommendations to promote psychosocial
      health in the workplace as a strategy to improve public health of the population.

PMID- 22858773
TI  - [Impact of high altitude on pregnancy and newborn parameters].
AB  - This review describes adverse outcomes in pregnancy after brief, intermittent, or
      permanent residence at high altitudes. Review of literature shows that congenital
      malformations rates are higher at high altitudes. Additionally, rates of
      stillbirths, small size for gestational age, and preeclampsia are increased in
      populations living at high altitudes and are associated with high maternal
      hemoglobin levels (>14.5 g/dl). In conclusion, a pregnant woman exposed briefly,
      intermittently, or permanently to high altitudes results in increased risk of
      adverse outcomes when compared to pregnancies observed at sea level.

PMID- 22858774
TI  - [Oral blastomycosis, laryngeal papillomatosis and esophageal tuberculosis].
AB  - Esophageal involvement is an extremely rare complication of tuberculosis even in
      countries with high prevalence of infection. We report the case of a 57 year-old
      hiv-seronegative patient with simultaneous diagnoses of oral blastomycosis and
      laryngeal papillomatosis. Both were confirmed by anatomopathological analysis.
      The esophageal biopsy revealed granulomatous esophagitis with necrosis and ziehl
      neelsen stain showed acid-fast alcohol resistant bacilli suggestive of
      tuberculosis. The patient's history included pulmonary tuberculosis twice and
      previous abandonment of therapy. Thus, it was necessary to use oral itraconazole
      combined with second-line anti-tuberculosis drugs administered through a
      gastrostomy tube. The clinical development was favorable.

PMID- 22858775
TI  - [Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report].
AB  - A 48-year old woman with a recent diagnosis of Graves' disease arrived at the
      emergency room with fever, palpitations, and a sore throat. Her regular treatment
      included methimazole. On admission, laboratory results showed suppressed TSH,
      elevated free thyroxine, and neutropenia. She was admitted and started on
      antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf). After
      ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT
      scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures
      from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus
      Flavus. Amphotericin B was started but then switched to voriconazole, with both
      treatments failing to result in clinical improvement. The patient died of multi
      organ failure.

PMID- 22858776
TI  - [Tuberculosis and public health: ?individual rights or collective rights?].
AB  - Tuberculosis (TB) persists as a major public health problem in our country. The
      appearance of resistant strains has complicated its control and questioned the
      appropriateness of the current measures towards prevention and control. An
      analysis from social determinants related to TB, converge on irregular treatment
      that generates disease persistence and appearance of resistance to TB drugs. The
      objective of this paper is to identify the role of the government in the
      treatment of TB patients, to recognize difficulties of treatment adherence
      considering that its fulfillment depends on the patient, despite that it has
      direct consequences on public health, and to discuss TB management alternatives
      with an approach based on individual and collective human rights. International
      literature shows limit experiences of individual rights and collective ones, but
      based on health policies and health legislation. In Peru, a new approach is
      required to guarantee population health without infringing individual rights.

PMID- 22858777
TI  - [Vaccines and autoimmunity: a strange association under debate].
AB  - The occurrence and significance of autoimmune manifestations after administration
      of vaccines remain controversial. Evidence for immunization triggered
      autoimmunity come from several sources including theoretical models, animal
      studies, single and multiple case reports. In contrast, several epidemiological
      studies don't report this association, which is reassuring and at least indicates
      that vaccines are not a major cause of autoimmune diseases. We analyzed current
      scientific data concluded that vaccines bring a positive impact on public health,
      so it is necessary to continue developing this technology. Evaluation methods
      should be improved to avoid or anticipate the possible autoimmune side effects
      that can be presented.

PMID- 22858778
TI  - [Actions for legionellosis prevention and control: a challenge for public health
      in Spain].
AB  - Legionellosis is a respiratory disease originating in systems that produce
      aerosol and contain Legionella sp. In recent decades, Spain has developed a
      regulatory framework for prevention and control of legionellosis. This article
      describes the epidemiology of legionellosis and the importance of controlling the
      transmission of bacteria in the fight against the disease. In that regard, it
      becomes clear the role of reviewing critical facilities and the inclusion of new
      ones in the preventive legislation, the estimation of risk, and the improvement
      in the diagnostic processes and progress in new prevention protocols.

PMID- 22858779
TI  - [Goals of occupational health and environmental protection at the beginning of
      the 21st century in Peru].

PMID- 22858780
TI  - [Environmental and social determinant factors for the reemergence of
      leptospirosis in the Amazon region of Peru, 2012].

PMID- 22858781
TI  - [History of Instituto Nacional de Salud Ocupacional del Peru].
AB  - In Peru, the industry's development has made economic improvements but at the
      same time, it has had a major impact on the health of the workers; for that
      reason, it was necessary to generate control mechanisms. So, in 1940 it was
      created the Departmento de Higiene Industrial, which in 1956 was changed to
      Instituto de Salud Ocupacional, but it was deactivated in 1994. However, in 2001
      it reappeared into the Ministerio de Salud organizational structure with the name
      of Instituto de Salud Ocupacional "Alberto Hurtado Abadia". Actually, it is the
      Centro Nacional de Salud Ocupacional y Proteccion del Ambiente para la Salud
      (CENSOPAS), organ of the Instituto Nacional de Salud which continues working in
      synergy with other institutions and sectors, making research to protect the
      health of exposed persons (workers and community) to contamination and risks
      associated with economic activities.

PMID- 22858782
TI  - [About the World Health Day, the social determinants and the opportunities].

PMID- 22858783
TI  - [Problems in medical prescriptions for the elderly in Peru].

PMID- 22858784
TI  - Ruthenium(II) bis(terpyridine) electron transfer complexes with alkynyl
      ferrocenyl bridges: synthesis, structures, and electrochemical and spectroscopic
      studies.
AB  - Two novel alkynyl-bridged symmetric bis-tridentate ligands 1,2-bis(1'-[4'
      (2,2':6',2''-terpyridinyl)]ferrocenyl)ethyne (3a; tpy-Fc-C[triple bond]C-Fc-tpy;
      Fc = ferrocenyl; tpy = terpyridyl) and 1,4-bis(1'-[4'-(2,2':6',2''
      terpyridinyl)]ferrocenyl)-1,3-butadiyne (3b; tpy-Fc-C[triple bond]C-C[triple
      bond]C-Fc-tpy) and their Ru(2+) complexes 6a and 6b have been synthesized and
      characterized by cyclic voltammetry, UV-vis and luminescence spectroscopy, and in
      the case of 3b by single-crystal X-ray diffraction. Cyclic voltammograms of both
      compounds, 3a and 3b, display two severely overlapping ferrocene-based oxidative
      peaks with only one reductive peak. The redox behavior of 6a and 6b is dominated
      by the Ru(2+)/Ru(3+) redox couple (E(1/2) from 1.33 to 1.34 V), the Fe(2+)/Fe(3+)
      redox couples (E(1/2) from 0.46 to 0.80 V), and the tpy/tpy(-)/tpy(2-) redox
      couples (E(1/2) from -1.19 to -1.48 V). The UV-vis spectra of 6a and 6b show
      absorption bands assigned to the (1)[(d(pi)(Fe))(6)] ->
      (1)[(d(pi)(Fe))(5)(pi*(tpy)(Ru))(1)] MMLCT transition at ~555 nm. Complexes and
      are luminescent in H(2)O-CH(3)CN (4 : 1, v/v) solution at room temperature, and
      6b exhibits the strongest luminescence intensity (lambda(max)(em): 710 nm,
      Phi(em): 2.28 * 10(-4), tau: 358 ns) relative to analogous ferrocene-based
      bis(terpyridine) Ru(II) complexes reported so far.

PMID- 22858785
TI  - "Thiol-ene" click chemistry: a facile and versatile route for the
      functionalization of porous polymer monoliths.
AB  - The preparation of porous polymer monoliths with dodecyl and zwitterionic
      functionalities via the "thiol-ene" click chemistry of thiol-containing monoliths
      with both hydrophobic and polar methacrylate "ene" monomers has been
      demonstrated. Selected separations confirmed the excellent potential of these
      monoliths in chromatography.

PMID- 22858786
TI  - Acute lumbar spinal pseudogout attack after instrumented surgery.
AB  - STUDY DESIGN: A case report. OBJECTIVE: An elderly patient presented with an
      acute lumbar spinal pseudogout attack after lumbar instrumented surgery. SUMMARY
      OF BACKGROUND DATA: Although gout and pseudogout are common diseases causing
      inflammatory arthropathy in peripheral joints, involvement of the spine is
      uncommon. Here, we report a patient experiencing an acute lumbar spinal
      pseudogout attack after lumbar instrumented surgery. METHODS: The patient was
      treated for lumbar spondylolisthesis at L4 and L5 level and afterward complained
      of lower back and bilateral leg pain. Conservative treatment was not effective
      for the patient; therefore, we preformed posterior transforaminal lumbar
      interbody fusion surgery. RESULTS: The postoperative course was uneventful;
      however, he experienced lower back pain 4 weeks after surgery. Magnetic resonance
      image showed changes in signal intensities of vertebra and fluid accumulation in
      posterior back muscles. A biopsy was performed, but the culture was negative for
      infection. Calcium pyrophosphate dehydrate was detected in the fluid. Thus,
      conservative therapy without antibiotics was performed, and the patient's
      symptoms disappeared within 2 weeks. CONCLUSION: Here, we reported the first case
      of acute lumbar spinal pseudogout attack after lumbar instrumented surgery. We
      recommend considering pseudogout before and after surgery.

PMID- 22858787
TI  - Delayed onset of anterior spinal artery syndrome after repair of aortic
      coarctation.
AB  - STUDY DESIGN: A case report. OBJECTIVE: We report a case of delayed anterior
      spinal artery syndrome after repair of aortic coarctation in which the symptoms
      did not appear until 6 months after surgery. SUMMARY OF BACKGROUND DATA: Residual
      dilatation of the anterior spinal artery after surgery can mimic a dilated
      intraspinal vein, which could lead to the erroneous diagnosis of spinal
      arteriovenous malformation as the cause for anterior spinal artery syndrome.
      METHODS: A 40-year-old man with a history of hypertension underwent surgical
      bypass of the left subclavian artery to descending thoracic aorta to treat
      coarctation of the thoracic aorta and had an uncomplicated postoperative course.
      Six months later, he developed numbness and weakness in his hands. Magnetic
      resonance image showed abnormal signal within the cervicothoracic spinal cord and
      prominent flow voids within the ventral spinal canal. Spinal digital subtraction
      angiography revealed slow flow in a dilated intraspinal vessel. Given the history
      of aortic coarctation repair, the possibility that this represented a residually
      dilated anterior spinal artery rather than an arteriovenous malformation was
      considered and confirmed on magnetic resonance imaging. RESULTS: In our patient,
      institution of an anticoagulation medication regime resulted in rapid improvement
      of neurological symptoms, underscoring the importance of the awareness of this
      phenomenon. CONCLUSION: Delayed anterior spinal artery syndrome after aortic
      coarctation repair because of anterior spinal artery thrombosis can manifest even
      6 months postoperatively. Careful analysis of pre- and postoperative cross
      sectional imaging should provide the correct diagnosis. Spinal digital
      subtraction angiography is probably unnecessary and must be interpreted with
      caution.

PMID- 22858788
TI  - Heterotopic ossification of the abdominal wall.
AB  - INTRODUCTION: Heterotopic ossification is a rare, benign condition which occurs
      when bone develops in tissues that do not normally ossify. PRESENTATION OF CASE:
      We herein report the case of a 73-year-old gentleman who underwent a laparotomy
      for a large splenic flexure tumour considered unresectable at initial
      intervention. Following delivery of chemotherapy, he was referred for a second
      opinion and the tumour with adjacent structures was removed at a subsequent
      laparotomy. A segment of abnormal hard tissue present in the abdominal wall was
      also excised. Histopathology revealed metaplastic bone deposition. DISCUSSION:
      Heterotopic ossification may occur at various sites and is a recognised but
      exceedingly infrequent sequela of abdominal surgery. CONCLUSION: This case
      highlights clinical, aetiological and histopathological features of this rare
      finding.

PMID- 22858789
TI  - Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen: Case report
      and review of the literature.
AB  - INTRODUCTION: Sclerosing Angiomatoid Nodular Transformation of the spleen (SANT)
      is a rare benign vascular lesion of the spleen with extensive sclerosis and
      unknown etiology. PRESENTATION OF CASE: We report a new case of SANT of the
      spleen found in a 53-year-old female following detection of a splenic mass on a
      routine computed tomography (CT). The patient underwent an uncomplicated
      laparoscopic splenectomy and the specimen was sent for histopathologic
      examination. DISCUSSION: A review of the 97 reported cases of SANT found in the
      literature was undertaken. There were 43 males and 54 females with a median age
      of 46 years (range: 11-82 years). SANT is classically considered to be a female
      predominant disease, however 44.3% of reported case were male and the gender
      predilection may soon be neutralized as more cases are reported. 65 of the 97
      (67%) patients were in 30-60 year age group. The majority of lesions (n=50) were
      incidentally found on imaging, and for those patients presenting with symptoms,
      abdominal pain (n=18) was the predominant symptom. CONCLUSION: The diagnosis of
      SANT should be considered in any patient presenting with a splenic lesion that
      contains an angiomatoid or inflammatory component. As the differential diagnosis
      for SANT includes malignant pathologies, and currently no reliable diagnostic
      radiological feature has been identified to differentiate between these
      conditions, SANT will continue to be diagnosed on the basis of surgical
      histopathology.

PMID- 22858790
TI  - The chameleon in the neck: Nodular fasciitis mimicking malignant neck mass of
      unknown primary.
AB  - INTRODUCTION: Difficulties with the correct diagnosis and treatment of nodular
      fasciitis in head and neck region has been reported in the literature. Nodular
      fasciitis was mistaken for sarcoma, papillary thyroid carcinoma, Burkitt's
      lymphoma, pleomorphic adenoma, or as a vascular lesion. PRESENTATION OF CASE: We
      present a patient with a single node in the neck with accelerated growth, which
      clinically appeared as a malignant epithelial tumor with unknown primary. The en
      bloc removal of the tumor and selective neck dissection was performed with
      bilateral tonsillectomy and biopsy of the tongue base. The histopathology
      revealed the tumor to be nodular fasciitis. No malignant cells were detected.
      DISCUSSION: Due to very rapid growth, its rich cellularity and high mitotic
      activity, nodular fasciitis can be mistaken as a malignant tumor. Trauma and/or
      infection is advocated to be a trigger for the formation of nodular fasciitis,
      although the exact aetiopathogenesis still remains unknown. Our patient admitted
      to regularly practicing martial arts with his opponent performing a specific
      combat maneuver applying pressure into the neck and submental region, which might
      have triggered the formation of the nodular fasciitis. CONCLUSION: Nodular
      fasciitis is a benign and often overlooked diagnosis in the head and neck region,
      that can be misinterpreted as a malignant tumor both clinically and
      histologically. A comprehensive medical history may help to avoid unnecessary
      radical treatment. If a malignancy cannot be confidently ruled out, the en bloc
      resection of the tumor with selective neck dissection may offer a safe option
      with low morbidity.

PMID- 22858791
TI  - A differential diagnosis in chronic lower abdominal pain.
AB  - INTRODUCTION: Spigelian hernias represent 0.12-2.4% of all abdominal wall
      hernias. Its diagnosis is elusive and requires a high level of conjecture given
      the disease rarity, vague associated abdominal complaints and frequent lack of
      consistent physical findings. PRESENTATION OF CASE: A 60-year-old woman presented
      with a history of chronic pain in the left lower side of the abdomen. The patient
      was treated for several diseases with no relief of symptoms. Abdominal ultrasound
      showed a Spigelian hernia in the lower left abdomen and surgery was scheduled for
      treatment. DISCUSSION: A SH is generally an inter-parietal hernia, meaning that
      the pre-peritoneal fat and the hernia sac penetrate the trasnversus abdominis and
      internal oblique muscles but remain behind the external oblique aponeurosis. In
      most of the patients the lack of clinical signs demands radiological
      investigation. That's the importance of the high grade of suspicious of the
      disease during the physical exam. The surgical repair is necessary due to the
      high risk of incarceration-related complications which can occur in up to 21% of
      cases. CONCLUSION: It's important to think in the Spigelian hernia as cause of
      lower abdominal pain to prompt indicate surgical repair and provide the patient's
      symptom relief. Also the type of repair is dependent on the surgeon's choice and
      also the means available in each center.

PMID- 22858792
TI  - A rare case of acute abdomen due to strangulated Waldayer's hernia.
AB  - INTRODUCTION: An internal hernia is the herniation of an intestinal segment into
      an intra-peritoneal fossa, is an uncommon cause for intestinal obstruction and is
      difficult to diagnose preoperatively. PRESENTATION OF CASE: We report a male
      patient 19 years old presenting with acute abdomen due to a strangulated
      Waldayer's hernia. DISCUSSION: The paraduodenal hernias are more common in males
      (M:F ratio 3:1). The average age at diagnosis is 38.5 years clinically presenting
      with chronic intermittent post-parandial abdominal pain. An accurate incidence of
      paraduodenal hernias in infancy and childhood is unknown, but is quite rare.
      CONCLUSION: Internal complicated hernias are difficult to diagnose and once
      discovered intra-operative anatomical variations are present with special
      attribution to the management of the hernia sac.

PMID- 22858793
TI  - Surgical treatment of a patient with lung cancer metastasized to the spine with
      EGFR mutation: A case report.
AB  - INTRODUCTION: The prognosis of patients with lung cancer metastasis to the spine
      is not very promising and a palliative approach is often suggested by scales such
      as the Tomita score. The choice of surgery for these patients is questionable
      based on the aggressiveness of the disease. However, certain patient
      characteristics can be sought out to determine if surgery is indicated.
      PRESENTATION OF CASE: Here, we present a case of a 59 year old male which
      consulted for back pain, numbness of the upper left thigh, and weakness
      corresponding to an L2 lesion. It was later discovered that he was suffering from
      non small cell lung cancer (adenocarcinoma) with a single metastasis to the spine
      at the level of L2. The patient also presented an EGFR mutation. Thus, the
      patient presented two good prognosis characteristics: adenocarcinoma and an EGFR
      mutation. DISCUSSION: An aggressive treatment was chosen. This included an EGFR
      inhibitor, surgical treatment, and radiotherapy thereafter. The patient had no
      complications due to surgery and to date, the patient has survived over 12 months
      and is free of any symptoms. This case demonstrates that surgical intervention
      can be considered for certain patients with lung cancer metastasized to the
      spine. CONCLUSION: This case demonstrates that surgical intervention can be
      considered for certain patients with lung cancer metastasized to the spine. We
      hope spine surgeons in general will start verifying the EGFR mutation status of
      adenocarcinoma lung cancer patients to determine if surgery is indicated.

PMID- 22858794
TI  - Patient-clinician information engagement improves adherence to colorectal cancer
      surveillance after curative treatment: results from a longitudinal study.
AB  - Introduction. Follow-up surveillance after curative treatment for colorectal
      cancer (CRC) patients is recommended to detect early cancer recurrences and
      improve survival outcomes. However, a substantial proportion of CRC patients do
      not undergo cancer surveillance. Several demographic and disease-related factors
      have been associated with cancer surveillance adherence. Thus far, patient
      centered communication has not been studied as a determinant for undergoing
      cancer surveillance. The purpose of this study is to determine whether patient
      clinician information engagement (PCIE) influences patients' self-reported
      adherence to recommended CRC surveillance procedures.  Methods. The study was a
      longitudinal survey among Pennsylvanian patients diagnosed with CRC in 2005. CRC
      patients who were eligible for surveillance and participated in both the baseline
      and 1-year follow-up surveys were included in this analysis (n = 305). The main
      outcome measure was self-reported adherence to physical examination,
      carcinoembryonic antigen testing, and colonoscopy according to recommended
      guidelines.  Results. Controlling for potential confounders, higher PCIE at
      baseline predicted a higher odds for CRC patients reporting adherence to
      recommended surveillance 1 year later by 2.8 times. Other significant predictors
      of adhering to recommended surveillance were a higher education level and having
      received systemic therapy.  Discussion. In this longitudinal study among CRC
      patients who received curative treatment, greater patient engagement with
      clinicians about cancer-related information was found to improve patients'
      subsequent adherence to recommended surveillance. This finding provides support
      for encouraging greater patient-physician communication among CRC patients.

PMID- 22858795
TI  - Lead acetate reduces the ability of human umbilical cord mesenchymal stem cells
      to support hematopoiesis in vitro.
AB  - Plumbum (Pb) is a heavy metal toxin that causes many pathophysiological effects
      in various systems of the human body. It has previously been reported that
      excessive lead trioxide causes hematopoietic system toxicity. Mesenchymal stem
      cells (MSCs), as cells with self-renewal and multipotent differentiation
      potential, play a supportive role in hematopoietic function. Lead is well known
      to interfere with hemoglobin synthesis and affect erythrocyte morphology and
      survival. MSCs and the cytokines secreted by MSCs are the important components of
      the hematopoietic microenvironment. Thus, we hypothesized that lead may cause
      damage to MSCs, which may provide a new understanding of the mechanism of lead
      toxicity in the hematopoietic system. In the present study, cell count, MTT
      assay, apoptosis assay, osteogenic differentiation, cell histochemical staining,
      cell cycle analysis, colony forming assay and RT-PCR were used. The results
      showed that the proliferation of umbilical cord MSCs (UCMSCs) was affected if the
      concentrations of lead were higher than 10 uM. Following osteogenic
      differentiation, the rate of alkaline phosphatase and Von Kossa stain positivity
      in the experimental group was lower than that in the control group. In
      conclusion, these results demonstrate that lead suppresses the self-renewal and
      multipotent differentiation potential of UCMSCs, and induces an adverse effect on
      the expression of UCMSCs cytokines. MSCs also have a hematopoiesis-promoting
      function that is capable of supporting colony formation of bone marrow cells.
      Furthermore, we found that following treatment with lead acetate, the supportive
      function of UCMSCs on colony formation was inhibited. Taken together, lead
      acetate has a toxic effect on the self-renewal, multipotent differentiation
      potential and hematopoiesis-promoting function of UCMSCs.

PMID- 22858796
TI  - Walking and talking in maintenance hemodialysis patients.
AB  - OBJECTIVES: To investigate whether there is a reduction in walking with the
      simultaneous performance of a cognitive task (ie, dual-task cost [DTC]) in
      persons undergoing hemodialysis (HD), and whether it is greater in persons
      undergoing HD compared with age-matched controls. DESIGN: Cohort. SETTING:
      University research laboratory. PARTICIPANTS: Persons undergoing HD (n=14; 5
      women, 9 men; mean age +/- SD, 50.0+/-11.8y) and age-matched controls (n=14; 4
      women, 10 men; mean age +/- SD, 48.5+/-10.1y) participated in the investigation.
      INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Participants walked at a
      self-selected pace on an electronic pathway, which recorded spatiotemporal
      parameters of gait, in 4 separate trials and completed a cognitive task in the
      last 2 trials. The DTC was quantified as the change in spatiotemporal parameters
      of gait from baseline to the cognitive trials. RESULTS: The HD group had a
      greater decrease in walking function during the cognitive task, with DTC ranging
      from 6% to 14%. On average, walking velocity decreased to less than 1m/s in HD
      patients during the cognitive condition. Baseline walking velocity was found to
      be moderately correlated with the magnitude of DTC of cadence and step time (rho=
      .44 and .46; P values <.05). CONCLUSIONS: Persons undergoing HD have greater
      interference between walking and talking compared with controls. Difficulty
      walking while thinking has implications for everyday life and may be related to
      the risk of falls. Further work is necessary to determine other contributing
      factors to elevated DTC in HD patients, and whether DTC can be reduced with
      targeted interventions.

PMID- 22858797
TI  - Assessing stroke patients for rehabilitation during the acute hospitalization:
      findings from the get with the guidelines-stroke program.
AB  - OBJECTIVE: To examine the frequency and determinants of an assessment for
      rehabilitation during the hospitalization for acute stroke. DESIGN: Prospective
      cohort of patients admitted with acute stroke in the Get With The Guidelines
      Stroke (GWTG-Stroke) program from January 8, 2008, to March 31, 2011. SETTING:
      Acute hospitals (n=1532) in the United States participating in the GWTG-Stroke
      program. PARTICIPANTS: Adults with a stroke diagnosis (N=616,982) from a GWTG
      Stroke-participating acute hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Documentation of an assessment for rehabilitation services during the
      acute hospitalization. RESULTS: Overall, almost 90% of stroke patients had
      documentation of an acute assessment for rehabilitation. In multivariable
      analysis, patients significantly more likely to be assessed for rehabilitation
      were younger, male, black or of other nonwhite races (Asian, American Indian,
      Alaska Native, Native Hawaiian, or Pacific Islander) when compared with white,
      independently ambulating before admission, and admitted from the community.
      Patients who received a stroke consult, cared for in a stroke unit, and treated
      in the northeast region of the United States were also more likely to be
      assessed. CONCLUSIONS: There is evidence that rehabilitation was considered for
      90% of acute stroke patients in this sample. Future research is needed to examine
      what assessments are conducted and by whom, and how these are used to determine
      the appropriate level of rehabilitation care for their needs.

PMID- 22858798
TI  - Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic
      susceptibility for type 2 diabetes.
AB  - Visceral adipose tissue (VAT) is a source of inflammatory cytokines that in obese
      subjects may contribute to low-level systemic inflammation and development of
      metabolic syndrome. Expansion of VAT involves adipocyte hyperplasia and
      hypertrophy and requires breakdown of the extracellular matrix and increased
      vascular outgrowth. To investigate changes of gene expression associated with VAT
      expansion and the role of combined genetics and diet, we implemented gene
      microarray analyses of VAT in NONcNZO10 (NZ10) and control SWR/J mice subjected
      to control chow (CD) or a diet of high protein and fish oil (HPO). NZ10 mice on
      CD showed increased body weight, hyperglycemia, and hyperinsulinemia at 25 weeks
      whereas those on HPO diet retained normal insulin levels and were normoglycemic.
      Two-way ANOVA revealed a significant interaction between diet and strain on blood
      glucose, serum insulin, and percent fat but not for body weight. Microarray heat
      maps revealed a remarkable combined effect of genetics and diet on genes that
      regulate extracellular matrix as well as angiogenic genes. Real time-PCR (RT-PCR)
      confirmed markedly increased expression of matrix metalloproteinases (MMPs) 2, 3,
      11, and 12, vascular endothelial growth factor-A and C (VEGF-A and C), Von
      Willebrand Factor, and peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) selectively in the NZ10/CD group. MMP7 was significantly decreased.
      Protein levels of MMP2, 3, and 9 were significantly increased in the VA of NZ10
      mice fed CD while those of MMP7 were downregulated. Microarrays also revealed
      diet-dependent two to fourfold increased expression of all four tissue inhibitor
      of metalloproteinases (TIMP) isoforms in NZ10 mice. Two-way ANOVA confirmed
      strongly interactive roles of diet and genetics on fat deposition and progression
      of type 2 diabetes in this polygenic mouse model.

PMID- 22858799
TI  - Efficacy of ultrasonography in identification of non-recurrent laryngeal nerve.
AB  - BACKGROUND: The aim of this prospective study was to identify the arterial
      anomalies constantly associated with nonrecurrent inferior laryngeal nerve by
      preoperative ultrasonography and impact on recurrent inferior laryngeal nerve
      palsy (RILN). METHOD: The study included 332 patients who underwent thyroidectomy
      or parathyroidectomy between 2009 February and 2011 October. Preoperative
      ultrasonography was performed to all patients to identify vascular anomalies
      related to NRILN. CT was performed only in patients with NRILN predicted with
      preoperative ultrasonography. Systematic nerve dissection was performed
      surgically. Patient characteristics, type of NRILN, preoperative and
      postoperative vocal cord mobility and morbidity were recorded. RESULTS: The NRILN
      was identified in 6 patients on the right side (1.94%). Preoperative
      ultrasonography predicted NRILN in all cases (accuracy 100%). CONCLUSION:
      Ultrasonography is a very reliable and simple method to be used in preoperative
      assessment to identify vascular anomaly associated with NRILN to make optimal
      surgical decisions against nerve damage in patients undergoing thyroidectomy or
      parathyroidectomy. Adequate surgical technique is of great importance.

PMID- 22858800
TI  - Feasibility of oncoplastic techniques in the surgical management of locally
      advanced breast cancer.
AB  - BACKGROUND: Locally advanced breast cancer (LABC) is still common in developing
      countries. The association between neoadjuvant chemotherapy (NC) and oncoplastic
      surgery (OS) might provide an oncological treatment with satisfactory aesthetic
      results. PURPOSE: The goal was to demonstrate if oncoplastic surgical techniques
      can be utilized to treat LABC which was submitted to neoadjuvant chemotherapy.
      METHODS: This prospective clinical trial included breast cancer patients,
      clinical stage III, who underwent established NC regimen. All patients underwent
      preoperative planning to control the tumor size and to define the surgical
      technique. A detailed analysis of the pathological specimen was performed.
      RESULTS: 50 patients were assessed and surgically treated. Tumor size ranged from
      3.0 to 14.0 cm (median 6.5 cm). Pathologic response was rated as stable,
      progressive, partial response, and complete response in 10%, 8%, 80% and 2% of
      the cases, respectively. Seventeen (34%) patients were submitted to OS. No
      patient had positive margins. Skin involvement was presented in 36% of pathologic
      specimen. CONCLUSIONS: Oncoplastic surgical techniques for selected patients
      decrease the rates of radical surgery despite large tumors.
      (www.clinicaltrials.gov, NCT00820690).

PMID- 22858801
TI  - Preparation and application of functionalized cellulose acetate/silica composite
      nanofibrous membrane via electrospinning for Cr(VI) ion removal from aqueous
      solution.
AB  - Novel NH(2)-functionalized cellulose acetate (CA)/silica composite nanofibrous
      membranes were successfully prepared by sol-gel combined with electrospinning
      technology. Tetraethoxysilane (TEOS) as a silica source, CA as precursor and 3
      ureidopropyltriethoxysilane as a coupling agent were used in membrane
      preparation. The membrane's chemical and morphological structures were
      investigated by scanning electron microscopy (SEM), high-resolution transmission
      electron microscopy (HRTEM) images, X-ray diffraction (XRD), element analyzer,
      Fourier-transform infrared spectroscopy (FTIR) and N(2) adsorption-desorption
      isotherms. The composite nanofibrous membranes exhibited high surface area and
      porosity. The membranes were used for Cr(VI) ion removal from aqueous solution
      through static and dynamic experiments. The adsorption behavior of Cr(VI) can be
      well described by the Langmuir adsorption model, and the maximum adsorption
      capacity for Cr(VI) is estimated to be 19.46 mg/g. The membrane can be
      conveniently regenerated by alkalization. Thus the composite membrane prepared
      from biodegradable raw material has potential applications in the field of water
      treatment.

PMID- 22858802
TI  - Anuran road-kills neighboring a peri-urban reserve in the Atlantic Forest,
      Brazil.
AB  - Mortality from road-kills may figure among the important causes of decline in
      amphibian populations and species extinctions worldwide. Evaluation of the
      magnitude, composition, and temporal and spatial distributions of amphibian road
      kills is a key step for mitigation planning, especially in peri-urban reserves.
      Once a month for 16 months, we surveyed, on foot, a 4.4 km section of state road
      ERS-389 bordering the Itapeva reserve in the southern Atlantic Forest. We
      recorded 1433 anuran road-kills and estimated a mortality rate of 9002 road
      kills/km/year. The species most often recorded were the largest ones:
      Leptodactylus latrans, Rhinella icterica, Leptodactylus gracilis and Hypsiboas
      faber; 54.5% of the carcasses could not be identified. Anuran mortality was
      concentrated in summer, and was associated with temperature, rainfall and
      photoperiod. Leptodactylus road-kills were strongly influenced by vehicle
      traffic, probably because of its high abundance during the entire study period.
      Road-kill hotspots differed for anurans as a group and for single species, and we
      found an association among spatial patterns of mortality and types of land cover,
      distance from the nearest waterbody, roadside ditches, and artificial light.
      Traffic should be banned temporarily during periods of high mortality, which can
      be forecasted based on meteorological data. A comprehensive mitigation approach
      should take into account hotspots of all anuran records, and also of target
      species for selecting locations for amphibian passages and fencing. Roadside
      ditches, artificial waterbodies, and conventional street lights should be reduced
      as much as possible, since they may represent ecological traps for anuran
      populations.

PMID- 22858803
TI  - Novel technologies for the formation of 2-D and 3-D droplet interface bilayer
      networks.
AB  - Droplet interface bilayer (DIB) networks have vast potential in the field of
      membrane biophysics, synthetic biology, and functional bio-electronics. However a
      technological bottleneck exists in network fabrication: existing methods are
      limited in terms of their automation, throughput, versatility, and ability to
      form well-defined 3-D networks. We have developed a series of novel and low-cost
      methodologies which address these limitations. The first involves building DIB
      networks around the contours of a microfluidic chip. The second uses flow rate
      and droplet size control to influence droplet packing geometries within a
      microfluidic chamber. The latter method enables the controlled formation of
      various 3-D network arrays consisting of thousands of interconnected symmetric
      and asymmetric lipid bilayers for the first time. Both approaches allow
      individual droplet position and composition to be controlled, paving the way for
      complex on-chip functional network synthesis.

PMID- 22858804
TI  - Organocatalytic asymmetric direct vinylogous Michael addition of alpha,beta
      unsaturated gamma-butyrolactam to nitroolefins.
AB  - The first organocatalytic enantioselective direct vinylogous Michael reaction of
      alpha,beta-unsaturated gamma-butyrolactam to nitroolefins is developed using
      cinchona alkaloids as the catalysts. Both product enantiomers are accessible with
      moderate to good enantioselectivity.

PMID- 22858805
TI  - Extracorporeal membrane oxygenation for extremely complicated scrub typhus.
AB  - Scrub typhus is a mite-borne disease caused by Orientia tsutsugamushi. Although
      early diagnosis and appropriate antibiotic therapy improve the prognosis for the
      majority of patients, life-threatening complications are not uncommon. Here, we
      present a case of successfully performed veno-veno type extracorporeal membrane
      oxygenation for scrub typhus-induced complications, including acute respiratory
      distress syndrome, sudden cardiac arrest, and multiorgan dysfunction. To our
      knowledge, this is the first case report of successful extracorporeal membrane
      oxygenation in complicated scrub typhus.

PMID- 22858806
TI  - Tacrolimus-based, steroid-free regimens in renal transplantation: 3-year follow
      up of the ATLAS trial.
AB  - BACKGROUND: Long-term use of corticosteroids is associated with considerable
      morbidity, including cardiovascular and metabolic adverse effects. METHODS: This
      study evaluated the long-term efficacy and safety of two steroid-free regimens
      compared with a triple immunosuppressive therapy in renal transplant recipients.
      This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter
      study. RESULTS: Data from 3 years were available for 421 (93.3%) of 451 patients
      in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas],
      139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids
      [triple therapy]). In the time interval from 6 months to 3 years after
      transplantation, the incidence of biopsy-proven acute rejection was low and
      similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection
      episodes occurred during the first 6 months of the study. Graft survival was high
      (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival
      (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12
      patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the
      study and similar between groups. There was a trend toward improved
      cardiovascular risk factors in the Tac/Bas group, including reduced total and low
      density lipoprotein cholesterol and lower new-onset insulin use. There were no
      between-group differences in the incidence or type of adverse events. CONCLUSION:
      Higher rates of acute rejection early in treatment were seen with the steroid
      free regimens, but this did not translate into poorer long-term outcomes, such as
      graft and patient survival and renal function. A trend for a more favorable
      cardiovascular risk profile was observed for steroid-free immunosuppression with
      Tac/Bas.

PMID- 22858807
TI  - A novel chiral ligand exchange capillary electrophoresis system with amino acid
      ionic liquid as ligand and its application in screening D-amino-acid oxidase
      inhibitors.
AB  - A novel amino acid ionic liquid (AAIL) with L-ornithine (L-Orn) as anion was
      successfully synthesized, and subsequently applied as an available chiral ligand
      coordinated with Zn(II) in a chiral ligand exchange capillary electrophoresis
      (CLE-CE) system for the enantioseparation of dansyl amino acids (Dns-D,L-AAs).
      The influence of key parameters, such as buffer pH, concentration ratio of Zn(II)
      to ligand and complex concentration, was investigated in detail. Eleven pairs of
      Dns-D,L-AAs enantiomers were baseline separated and three pairs were partly
      separated under the optimum conditions. For exploring its potential application,
      the quantitative features of this proposed method were studied. Good linearity
      (r(2) = 0.999) and favorable repeatability (RSD <= 3.4%) were obtained by using
      Dns-D,L-Met as the test analyte. Finally, this method was employed to investigate
      the inhibition efficiency of d-amino acid oxidase (DAAO) inhibitors, which may
      pave a new way for the high-throughput screening of enzyme inhibitors and
      relevant drug discovery.

PMID- 22858808
TI  - Versatile coordination behaviour of an asymmetric half-salen ligand bearing a
      dansyl fluorophore.
AB  - The coordinative chemistry of the tridentate half-salen ligand 5-(dimethylamino)
      N-(2-((2-hydroxybenzylidene)amino)phenyl)naphthalene-1-sulfonamide (H(2)L, 1) has
      been studied by means of an electrochemical method. All of the complexes have
      been characterised using analytical and spectroscopic techniques. Ligand 1 and
      two nickel (6 and 7), copper (9), zinc (12) and cadmium (14) metal complexes have
      been studied by crystallography. Complexes 6 and 7 are octahedral and tetrahedral
      nickel(II) complexes, respectively, and both contain an [L](2-) molecule that
      behaves in an [N(2)O] tridentate manner. Nickel(II) completes its coordination
      kernel with three water molecules in complex 6, whereas in complex 7 the nickel
      ion is further bound to a molecule of dansylamine arising from a hydrolysis
      process. The copper(II) complex 9 is a monomeric compound that contains a
      bideprotonated ligand thread and a dimethylsulfoxide molecule coordinated through
      the sulfur atom. The zinc complex 12 is an unusual pentanuclear cluster compound
      whose structure consists of four anionic ligand units and two hydroxo anions
      bound to five zinc(II) centres. The appearance of the hydroxo anions in this
      complex provides new evidence for water reduction electrochemically promoted by
      zinc metal under mild conditions. The cadmium complex 14 is a dimeric compound
      that comprises two molecules of the anionic ligand and two dimethylsulfoxide
      molecules. The great structural variety exhibited by all these complexes
      demonstrates that the introduction of asymmetry in a salen skeleton by
      incorporating a dansyl pendant increases the versatility of the resulting ligand
      on coordination. All complexes are luminescent in solution at room temperature in
      acetonitrile solutions.

PMID- 22858809
TI  - Treatment of systematized epidermal nevi using the ultrasonic surgical aspirator.

PMID- 22858810
TI  - [Cost-effectiveness of vaccinating pregnant women against pandemic influenza in
      Colombia].
AB  - OBJECTIVE: Estimating the cost-effectiveness ratio of vaccinating pregnant women
      against the 2009 pandemic influenza A (H1N1) in Colombia during the second wave
      of the pandemic. METHODS: A decision tree was constructed, which simulated the
      health results (deaths and years of potential life lost [YPLL]) in two cohorts of
      pregnant women; one vaccinated, the other unvaccinated. The model's parameters
      were drawn from scientific literature and costs were estimated on the basis of a
      previous study. Incremental cost-effectiveness ratios (ICER) were calculated.
      RESULTS: Vaccinating pregnant women against pandemic flu would have prevented
      between 4 664 and 15 741 outpatient visits and between 119 and 401
      hospitalizations. Between US$ 249 530 and US$ 842 163 in costs of care would have
      been avoided. For the base scenario, vaccinating pregnant women would be cost
      effective (ICER/YPLL avoided US$ 7 657). This ICER was responsive to the
      disease's fatality rate; vaccination would not be cost-effective in Colombia in
      scenarios with a lower fatality rate. CONCLUSIONS: Vaccinating pregnant women
      against pandemic influenza is cost-effective in a scenario with a high mortality
      rate. The existing evidence that pregnant women are at increased risk of
      complications and that the vaccine is safe would justify its use in pregnant
      women.

PMID- 22858811
TI  - User satisfaction with the Family Health Program in Vespasiano, Minas Gerais,
      Brazil.
AB  - OBJECTIVE: To assess factors influencing perspectives on Brazil's national Family
      Health Program (PSF) by exploring satisfaction with PSF units and home-visit
      community health agents and perceptions about PSF unit accessibility among
      frequent users (primary caretakers of children under age 5) in Vespasiano, Minas
      Gerais. METHODS: Data were collected though cross-sectional household surveys to
      determine programmatic and demographic factors affecting user satisfaction with
      the PSF. Multivariate logistic modeling was used to estimate users' satisfaction
      with PSF units and agents and perceived access to PSF unit services. Chi-square
      and analysis of variance (ANOVA) tests were used to estimate statistical
      differences. RESULTS: The majority of caretakers were satisfied with both their
      PSF unit and their PSF community health agent and had received at least one
      monthly home visit from the health agent. Satisfaction with both the health agent
      and the unit was positively associated with perceived access to the unit and
      frequency of agent home visits. Caretakers who reported that their PSF agent made
      one or more home visits per month were more likely to perceive the PSF unit as
      being "accessible" (or "sometimes accessible"). CONCLUSIONS: The current data are
      important indicators of population health in Minas Gerais, Brazil, and suggest
      that users' satisfaction with the PSF and perceptions about its accessibility can
      be improved by ensuring that all households receive at least one health agent
      home visit per month. These results could be applied to other parts of Brazil or
      Latin America to improve understanding of user perceptions of health systems.

PMID- 22858812
TI  - [Delays in the diagnosis of tuberculosis in a town at the triple border of
      Brazil, Paraguay, and Argentina].
AB  - OBJECTIVE: To identify the factors linked to patients and health services in
      delays in the diagnosis of tuberculosis. METHODS: Epidemiological study in Foz do
      Iguacu, Parana, Brazil, 2009. The Primary Care Assessment Tool, adapted for
      appraising tuberculosis treatment, was the instrument used. Descriptive
      statistics techniques were used, such as frequency distributions, central
      tendency and dispersion measurements (median and interquartile intervals), and
      odds ratios. RESULTS: There were greater delays in seeking health services for
      those in the age group 60 years and older, for females, for patients with low
      levels of education, and for patients with poor knowledge of the disease.
      Clinical variables (being a new case and HIV infection) and behavioral variables
      (use of tobacco and alcohol consumption) were not linked with delays in
      diagnosis. The median time delays before diagnosis attributable to patients and
      to the health services were 30 days and 10 days, respectively. Emergency 24-hour
      medical services and primary health care services were not effective in
      identifying suspicious cases of tuberculosis and requesting tests to confirm the
      diagnosis, with a high percentage of referrals to the Tuberculosis Control
      Program clinic. CONCLUSIONS: Going to primary health care services for diagnosis
      increased the time before diagnosis of the disease was reached. The Tuberculosis
      Control Program clinic was more effective in diagnosis of tuberculosis, due to
      the training of the staff and to an organized process for receiving patients,
      including the availability of tests to support the diagnosis.

PMID- 22858813
TI  - [Infant mortality due to congenital malformations and socioeconomic status: the
      case of Argentina].
AB  - OBJECTIVE: Compare the infant mortality rate due to congenital malformations (
      IMRCM) and the percentage of deaths due to congenital malformations (%DCM) with
      sociodemographic and economic characteristics in Argentina. METHODS: The
      Argentine study population resided in 511 departments of 23 provinces, grouped
      into five geographic regions (Northwest, Northeast, Central, Cuyo, and
      Patagonia). The analyzed variables were the IMRCM and the %DCM calculated on the
      basis of births and deaths during 2002-2006 period. In addition, 21 variables
      were used from the 2001 Population and Housing Census (National Census and
      Statistics Institute of Argentina) to construct the Sociodemographic and Economic
      Indicator (SDEI) through the analysis of principal components. Comparison tests
      were carried out in order to assess the significant differences among the various
      regions and the correlations between indicators, and of these with the
      departmental latitudes and longitudes. RESULTS: There was no significant
      correlation between the IMRCM and the SDEI, nor with geographic coordinates.
      However, there was a significant positive correlation between the IMRCM and the
      SDEI (P < 0.05) at all levels of political organization. The SDEI explained 41%
      of the %DCM. CONCLUSIONS: The IMRCM was not significantly associated with the
      country's marked socioeconomic heterogeneity; the highest %DCM values, on the
      other hand, were observed in the populations of the central and southern areas of
      the country. Given the relationship between the %DCM and socioeconomic
      development of the population, use of this indicator as a proxy of well-being and
      quality of life is suggested.

PMID- 22858814
TI  - A cluster-randomized controlled trial of handrubs for prevention of infectious
      diseases among children in Colombia.
AB  - OBJECTIVE: To evaluate the effectiveness of alcohol-based handrubs (ABH) in
      reducing acute diarrheal diseases (ADD) and acute respiratory infections (ARI)
      among children 1-5 years of age in childcare centers with limited tap water.
      METHODS: This was the first cluster-randomized controlled trial in a developing
      country. The study took place at 42 childcare centers with sporadic and limited
      water availability in six towns in Colombia. Participants were randomly assigned
      to use ABH as a complement to handwashing (intervention arm: 21 centers/794
      children); or to continue existing handwashing practices (control arm: 21
      centers/933 children). ADD and ARI cases were identified through teacher-reported
      signs and symptoms of illness. Adverse events were monitored. Hazard ratios (HR)
      were obtained using Cox proportional hazards multivariate regression shared
      frailty models. RESULTS: Child-days of surveillance totaled 336 038. Loss to
      follow up was 14.5%. For both ADD and ARI, there were no differences in hazard
      ratios during the first trimester of the study. In the second and third
      trimesters, significant reductions in the risk of ADD were found in the
      intervention compared to control arm (HR = 0.55, P < 0.001 and HR = 0.44, P <
      0.001, respectively). There were also significant risk reductions for ARI in the
      second trimester (HR = 0.80, P < 0.05) and in the third trimester (HR = 0.69, P <
      0.001). No adverse events occurred. CONCLUSIONS: ABH effectively prevent ADD and
      ARI, and are safe. Colombia's national public health policies for prevention of
      these diseases should include use of ABH, especially in settings where
      handwashing with soap and water is limited by water availability.

PMID- 22858815
TI  - A profile of patients treated at a national leprosy outpatient referral clinic in
      Rio de Janeiro, Brazil, 1986-2007.
AB  - OBJECTIVE: To analyze a profile of patients treated at a national leprosy
      outpatient referral clinic in metropolitan Rio de Janeiro, Brazil, over a period
      of more than two decades, and the subgroup of nationally registered leprosy cases
      from the same residential area, as well as all registered cases statewide.
      METHODS: An observational, descriptive analysis was carried out for patients
      treated from 1986 to 2007 at the Souza Araujo Outpatient Clinic (Ambulatorio
      Souza Araujo, ASA), a national referral center for the diagnosis and treatment of
      leprosy at the Oswaldo Cruz Foundation (Fiocruz) that serves clients from the
      city of Rio de Janeiro and other municipalities in the metropolitan area of Rio
      de Janeiro State. Demographic and clinical data for the subgroup of leprosy cases
      registered with Brazil's National Disease Notification System (Sistema Nacional
      de Informacao de Agravos de Notificacao, SINAN) between 2001 and 2007 and
      residing in the same municipalities as the ASA patients, and for all registered
      cases statewide, were also analyzed. RESULTS: Among the ASA patients, there was a
      decrease in average family income (from 3.9 to 2.7 times the minimum salary
      between the periods 1998-2002 and 2003-2007); the proportion of multibacillary
      (MB) patients (from 52.7% to 46.9%); and the proportion of patients younger than
      15 years old (from 12.8% to 8.7%). Among the MB patients, the average initial and
      final bacilloscopic indices were significantly higher in 2003-2007. Compared with
      the SINAN cases, more ASA cases involved disability and were younger than 15
      years old. CONCLUSIONS: Patients living with leprosy in the metropolitan area of
      the state of Rio de Janeiro belong to the most deprived social strata and have
      not benefited from the overall improvement in socioeconomic conditions in Brazil.

PMID- 22858816
TI  - Variation of cervical cancer incidence in Latin America and the Caribbean.
AB  - OBJECTIVE: To provide a comprehensive analysis of the descriptive epidemiology of
      invasive cervical cancer in Latin America and the Caribbean by analyzing quality
      data from the area's cancer registries, including data that were excluded from
      the International Agency for Research on Cancer (IARC) publication, Cancer
      Incidence in Five Continents, Vol. IX (CI5-IX). METHODS: This was a descriptive
      epidemiologic study that involved 20 cancer registries, 9 of which were included
      by IARC in CI5-IX, and 11 of which were not. Data on invasive cervical cancers
      diagnosed from 1998-2002 were obtained from IARC. A cervical cancer-specific
      quality assessment was performed on all registries whether or not they were
      included in CI5-IX. Data from 14 registries met quality criteria and were
      analyzed. Incidence rates were calculated and compared across registries.
      RESULTS: A substantial variation in incidence rates existed among the registries;
      age-standardized rates ranged from 14.6-44.0 per 100 000 women per year. Mean
      cervical cancer incidence rates were 10.4% higher for registries included in CI5
      IX than for those excluded; however, this difference was not significant (P =
      0.541). CONCLUSIONS: This study compared cervical cancer rates from a more
      diverse group of Latin American and Caribbean countries than that of the CI5-IX.
      The heterogeneity found among registries highlights the importance of examining
      data from as many registries as possible when characterizing risk across a
      geographic area. Data from developing countries can be used to better understand
      cancer distribution and enable Region-specific recommendations on cancer control
      and prevention once data quality has been established.

PMID- 22858817
TI  - [Analysis of quality of life following hospital discharge among survivors of
      severe sepsis and septic shock].
AB  - OBJECTIVE: Describe the impact of severe sepsis and septic shock on patients'
      quality of life following hospital discharge. METHODS: A controlled study
      conducted in two general hospitals of Joinville, Santa Catarina, Brazil, of in
      patients with severe sepsis or septic shock during the period of August 2005
      through November 2007. The patients were contacted by telephone between June and
      November 2009. The study group responded to Short Form-36, a questionnaire on the
      quality of life, two years after being discharged from hospital. The
      questionnaire was also answered by a control group composed of people who lived
      at the same residence as the study subjects, had no recent hospitalization, and
      were close in age. RESULTS: Of 217 patients with severe sepsis or septic shock,
      112 (51.6%) survived hospitalization. The survival rate after hospital discharge
      was 41.02% at 180 days, 37.4% at one year, 34.3% at 18 months, and 32.3% in two
      years. Thirty-six survivors responded to Short Form-36. There were declines in
      the quality of life for survivors (No. = 36) in comparison to the control group
      (No. = 36) in the following areas: physical functioning (59 +/- 32 versus 91 +/-
      18; P < 0.001), vitality (48 +/- 13 versus 59 +/- 14; P < 0.008), mental health
      (48 +/- 13 versus 59 +/- 14; P < 0.03), bodily pain (50 +/- 26 versus 76 +/- 16;
      P < 0.001), general health perceptions (53 +/- 18 versus 67 +/- 13; P < 0.004),
      physical role functioning (67 +/- 45 versus 85 +/- 34; P < 0.05), and social role
      functioning (70 +/- 28 versus 90. +/- 16; P < 0.05). CONCLUSIONS: Severe sepsis
      or septic shock can result in significant negative effects on the quality of
      life, in addition to reducing long-term survival probability.

PMID- 22858818
TI  - Influenza among adults in Latin America, current status, and future directions: a
      consensus statement.
AB  - In Latin America, adult influenza is a serious disease that exacts a heavy burden
      in terms of morbidity, mortality, and cost. Although much has been written about
      the disease itself, relatively little information has been compiled on what could
      be done to reduce its impact across the region, particularly from the perspective
      of clinicians with first-hand experience in confronting its effects. To fill this
      data gap, in 2011, the Pan American Health and Education Foundation (PAHEF) and
      the U.S.-based nonprofit Fighting Infectious Diseases in Emerging Countries
      (FIDEC) organized a conference and convened a panel of Latin American scientist
      clinicians with experience and expertise in adult influenza in the region tol)
      discuss the major issues related to the disease and 2) develop and produce a
      consensus statement summarizing its impact as well as current efforts to
      diagnose, prevent, and treat it. The consensus panel concluded a more concerted
      and better-coordinated effort was needed to reduce the adverse impact of seasonal
      influenza and future pandemics, including more surveillance, more active
      involvement by both governmental and nongovernmental organizations, and a much
      greater effort to vaccinate more adults, especially those at high risk of
      contracting the disease. In addition, a new approach for diagnosing influenza was
      recommended.

PMID- 22858819
TI  - [Organic foods and human health: a study of controversies].
AB  - The study of controversies is a methodological tool that generates knowledge
      about the social and political dimensions of science. This approach can be used
      to understand and explore the topic of organic foods. The present study aimed to
      analyze the controversies regarding the status of organic foods. We carried out a
      review of studies published since 1990 in three websites: International
      Foundation for Organic Agriculture, Soil Association, and Food and Agriculture
      Organization. The following controversies were identified: 1) effects on human
      health of the presence of chemical contaminants in organic foods; 2) the quality
      of organic foods as compared to conventionally grown foods; and 3) price of
      organic foods. Based on this review, it is possible to conclude that, even though
      organic foods stand out for their low toxicity, higher durability, and
      nutritional content of some items, more comparative studies are required to
      confirm the nutritional superiority of organic foods and to solve the
      controversies. The discussion must be contextualized within a broad spectrum of
      health promotion, in which organic farming appears associated with the support
      for small farming, biodiversity, and local sustainable development, so as to
      increase offer and demand for organic products at fair prices for individual and
      institutional consumers.

PMID- 22858820
TI  - [A school program for dengue control in Honduras: from knowledge to action].
AB  - The Environmental School Program (PEA, for its Spanish acronym), a dengue control
      initiative focused on primary schools that took place during 2005-2010 in several
      cities in Honduras, is described. The environmental health program was designed
      to increase knowledge and develop skills in the identification and control of
      Aedes aegypti breeding sites, as well as in water and solid waste management. The
      results, as measured by behavioral change and reduced larval indices, were
      satisfactory in the majority of the participating schools. The initiative
      involved not only children, but also their parents and teachers. In addition to
      reducing larval indices, PEA was successful in promoting community participation
      in environmental issues, particularly Aedes control. The inclusion of this
      educational content in the primary school curriculum in Honduras remains pending.

PMID- 22858821
TI  - Biobanking for health research in Brazil: present challenges and future
      directions.
AB  - This article outlines and discusses Brazil's new regulations on the use of human
      biological materials for research, specifically, Resolution CNS 441/11, enacted
      by the National Health Council of Brazil in May 2011, and the National Guidelines
      for Biorepositories and Biobanks (Ordinance No. 2201) published by the Ministry
      of Health in September 2011. The authors examine the differences between sample
      collections for single studies and large-scale collections for multiple studies
      (e.g., the National Tumor Bank at the Brazilian National Cancer Institute and the
      A. C. Camargo Hospital Biobank). Also discussed are the ethical and operational
      implications, i.e.,informed consent process, strategies for sample collection,
      custodianship, access to samples, and rules for disposal. Insights gained may be
      useful for developing national biobanking regulations in other countries in Latin
      America.

PMID- 22858822
TI  - [The family, foundation and primary link of public health of the future].

PMID- 22858823
TI  - [Patient safety: a component of health policies that must be strengthened in
      Latin America].

PMID- 22858824
TI  - The stability of the SEI layer, surface composition and the oxidation state of
      transition metals at the electrolyte-cathode interface impacted by the
      electrochemical cycling: X-ray photoelectron spectroscopy investigation.
AB  - The stability of the valence state of the 3d transition metal ions and the
      stoichiometry of LiMO(2) (M = Co, Ni, Mn) layered oxides at the surface
      electrolyte interface plays a crucial role in energy storage applications. The
      surface oxidation/reduction of the cations caused by the contact of the solids to
      air or to the electrolyte results in the blocking of the Li-transport through the
      interface that leads to the fast batteries deterioration. The influence of the
      end-of-charge voltage on the chemical composition and the oxidation state of 3d
      transition metal ions, as well as the stability of the solid-electrolyte
      interface formed during the electrochemical Li-deintercalation/intercalation of
      the LiCoO(2) and Li(Ni,Mn,Co)O(2), have been investigated by X-ray photoelectron
      spectroscopy. While the chemical composition of the solid-electrolyte interface
      is similar for both layered oxide surfaces, the electrochemical cycling to some
      critical voltage values leads to the disappearance of the interface. By the
      analysis of the shape of the 2p and 3s photoelectron emissions we show that the
      formation of the solid-electrolyte interface layer correlates with the partial
      reduction of the trivalent Co ions at the electrolyte-LiCoO(2) interface and the
      amount of the Co(2+) ions is increased as the solid-electrolyte interface
      vanishes. In contrast, the Mn(4+), Co(3+) and Ni(2+) ions of the Li(Ni,Mn,Co)O(2)
      are stable at the interface under the electrochemical cycling to higher end-of
      charge voltage. A correlation between deterioration of the LiCoO(2) and
      Li(Ni,Mn,Co)O(2) batteries and the change of electronic structure at the
      surface/interface after the electrochemical cycling has been found. The
      dissolution of the solid-electrolyte interface layer might be the reason for the
      fast deterioration of the Li-ion batteries.

PMID- 22858825
TI  - Polydatin alleviates non-alcoholic fatty liver disease in rats by inhibiting the
      expression of TNF-alpha and SREBP-1c.
AB  - The pathophysiology of non-alcoholic fatty liver disease remains incompletely
      elucidated, and available treatments are not entirely satisfactory. Polydatin, a
      stilbenoid compound derived from the rhizome of Polygonum cuspidatum, has been
      recognised to possess hepatoprotective and anti-inflammatory activities. The
      purpose of the present study was to determine whether polydatin has a protective
      effect against hepatic steatosis induced by a high-fat diet (HFD) and to
      elucidate its underlying molecular mechanisms in rats. Male Sprague-Dawley rats
      were randomly divided into four groups, including normal control, HFD model and
      polydatin-treated groups with polydatin levels of 30 and 90 mg/kg. Following the
      experimental period, plasma total cholesterol (TC), triglyceride (TG) and hepatic
      lipid concentrations were determined. To identify a possible mechanism, we
      examined the changes in liver tumor necrosis factor-alpha (TNF-alpha), lipid
      peroxidation levels and sterol-regulatory element binding protein (SREBP-1c) mRNA
      and its target genes. Both 30 and 90 mg/kg polydatin treatment alleviated hepatic
      steatosis and reduced plasma and liver TG, TC and free fatty acid (FFA)
      concentration significantly in HFD rats. In addition, TNF-alpha, and
      malondialdehyde and 4-hexanonenal levels were markedly suppressed by polydatin in
      the liver of HFD-fed rats. Polydatin also decreased the gene expression of SREBP
      1c and its target genes involved in lipogenesis, including fatty acid synthase
      (FAS) and stearoly-CoA desaturase 1 (SCD1) in HFD-fed rats. These results suggest
      that the protective effects of polydatin against HFD-induced hepatic steatosis
      may be partly associated with reduced liver TNF-alpha expression, lipid
      peroxidation level and SREBP-1c-mediated lipogenesis.

PMID- 22858826
TI  - A plethora of plasmonics from the laboratory for nanophotonics at Rice
      University.
AB  - The study of the surface plasmons of noble metals has emerged as one of the most
      rapidly growing and dynamic topics in nanoscience. Key advances in the synthesis
      of noble metal nanoparticles and nanostructures have resulted in a broad variety
      of structures whose geometries can be controlled systematically at the nanoscale.
      Arising from these efforts is a new level of insight and understanding regarding
      the fundamental properties of localized plasmons supported by these structures,
      and, in particular, the properties of interacting plasmon systems. This
      additional insight has led to the design of plasmonic systems that support
      coherent phenomena, such as Fano resonances. A broad range of applications are
      emerging for these structures: single- nanoparticle and nanogap chemical sensors,
      low-loss plasmon waveguides, and active plasmonic devices and detectors.
      Applications in biomedicine that exploit the strong photothermal response of
      nanoparticle plasmons have developed and advanced into clinical trials. The
      Laboratory for Nanophotonics at Rice has been home to many of these advances.
      Here, we showcase a variety of functional plasmonic materials and nanodevices
      emerging from our individual and collaborative efforts.

PMID- 22858828
TI  - Genome sequence of the oleaginous red yeast Rhodosporidium toruloides MTCC 457.
AB  - We report the de novo assembled 20.05-Mb draft genome of the red yeast
      Rhodosporidium toruloides MTCC 457, predicted to encode 5,993 proteins, 4 rRNAs,
      and 125 tRNAs. Proteins known to be unique to oleaginous fungi are present among
      the predicted proteins. The genome sequence will be valuable for molecular
      genetic analysis and manipulation of lipid accumulation in this yeast and for
      developing it as a potential host for biofuel production.

PMID- 22858829
TI  - Single neuron capture and axonal development in three-dimensional microscale
      hydrogels.
AB  - Autapse is an unusual type of synapse generated by a neuron on itself. The
      ability to monitor axonal growth of single neurons and autapse formation in three
      dimensions (3D) may provide fundamental information relating to many cellular
      processes, such as axonal development, synaptic plasticity and neural signal
      transmission. However, monitoring such growth is technically challenging due to
      the requirement for precise capture and long-term analysis of single neurons in
      3D. Herein, we present a simple two-step photolithography method to efficiently
      capture single cells in microscale gelatin methacrylate hydrogel rings. We
      applied this method to capture and culture single neurons. The results
      demonstrated that neural axons grew and consequently formed axonal circles,
      indicating that our method could be an enabling tool to analyze axonal
      development and autapse formation. This method holds great potential for impact
      in multiple areas, such as neuroscience, cancer biology, and stem cell biology.

PMID- 22858830
TI  - Ageing with spinal cord lesion permits a good quality of life!

PMID- 22858831
TI  - The emerging application of remote ischemic conditioning in the clinical arena.
AB  - Remote ischemic conditioning (RIC) is an intervention, in which intermittent
      episodes of ischemia and reperfusion in an organ or tissue distant from the
      target organ requiring protection, provide armour against lethal ischemia
      reperfusion injury. Although the exact mechanisms underlying the protection
      mediated through RIC have not been clearly established, the release of humoral
      factors and the activation of neural pathways have been implicated. There is now
      clinical evidence suggesting that this form of protection can be induced by a
      simple, noninvasive, and cost-effective procedure such as inflation and deflation
      of a blood pressure cuff and that this intervention provides increased organ
      protection in a variety of clinical scenarios, for example, in myocardial
      infarction. Here we provide an overview of the history and evolution of RIC, the
      potential mechanisms underlying its protective effects, and published randomized
      clinical trials in cardiovascular procedures.

PMID- 22858832
TI  - Local targets for immune therapy to cancer: tumor draining lymph nodes and tumor
      microenvironment.
AB  - In recent years, it has become apparent that immunoregulatory processes influence
      cancer development. The key players in tumor progression are mainly present in
      the microenvironment of the tumor and the draining lymph nodes. Interventions
      aimed at shifting tumor-promoting actions toward effective tumor-eradicating
      immunity are thus foremost required locally. As immune-modulating therapy has
      been shown to cause many adverse side effects when administered systemically, we
      strongly advocate the further development of local treatment for cancer
      immunotherapy.

PMID- 22858833
TI  - Physicochemical conditions and metal ion profiles in the gut of the fungus
      growing termite Odontotermes formosanus.
AB  - The physicochemical conditions in an insect's gut microenvironment have been
      reported to play an important role in food processing and metabolisms. In this
      study, the profiles of oxygen, pH, redox potentials, and hydrogen in the isolated
      guts of the fungus-growing termite, Odontotermes formosanus Shiraki, were
      investigated with a microeletrode system. Compared with those in other termites,
      O. formosanus exhibited a relatively lower oxygen partial pressures in its gut
      system ranging from 0 to 8.6 kPa. The pH profile in the different gut
      compartments was neutral (pH 6.1-7.4) except in the rectum region. The average
      redox potentials at the center of each gut region (except rectum) were high and
      ranged from approximately +70 to +310 mV. Especially, as the central intermediate
      during lignocellulose degradation, hydrogen partial pressures in the hindgut
      paunch lumen were recorded as high as 10.4 kPa. Furthermore, thirteen metal ion
      concentrations in the termite's gut system, nest symbiotic fungal combs, as well
      as the nest soil samples were evaluated with Inductively Coupled Plasma Mass
      Spectrometry (ICP-MS), which indicated that six metal ions (K, Mg, Mn, Ba, Se,
      and Mo) out of 13 ions recorded in the major digestive tract regions show some
      significant differences in their spatial distributions. A significant enrichment
      of some metal ions was also observed in the rectum, fungal combs, and the nest
      soil samples. The lower oxygen profiles, neutral pH, higher redox potentials, and
      higher hydrogen accumulation with the characterized spatial distributions for
      metal ions in the digestive tract of O. formosanus, highlighted the most
      important distinctiveness of the fungus-growing termites in its gut
      microenvironments, suggesting that the unique structure and functions of the
      intestinal ecosystem may present within its gut.

PMID- 22858834
TI  - Copper(II) fluorophosphates.
AB  - Eleven new copper fluorophosphate frameworks have been synthesised hydrothermally
      in a fluoride-rich medium, through the use of CuF(2) HPF(6) and monovalent metal
      fluorides as reactants. Products have been structurally characterised using
      single crystal X-ray diffraction. Reaction in fluoride-rich conditions produces
      chain, layer and three dimensional framework structures containing new and
      unusual structural features based on the linking of PO(3)F, PO(2)(OH,F)(2) and
      Cu(O,F)(n) polyhedra (n = 4-6). Analysis of these structures, in terms of the
      copper coordination environments and their linkage dimensionalities, shows that
      these features are dependent on fluoride-content of the reaction medium and,
      therefore, the level of fluoride ion incorporation into the product materials.
      Structures exhibiting inter-layer spaces and channels frequently have these lined
      by terminal fluoride anions of the PO(3)F, PO(2)(OH,F)(2) and Cu(O,F)(n)
      polyhedra.

PMID- 22858835
TI  - Investigating the oxidation of alkenes by non-heme iron enzyme mimics.
AB  - Iron is emerging as a key player in the search for efficient and environmentally
      benign methods for the functionalisation of C-H bonds. Non-heme iron enzymes
      catalyse a diverse array of oxidative chemistry in nature, and small-molecule
      complexes designed to mimic the non-heme iron active site have great potential as
      C-H activation catalysts. Herein we report the synthesis of a series of organic
      ligands that incorporate key features of the non-heme iron active site. Iron(II)
      complexes of these ligands have been generated in situ and their ability to
      promote hydrocarbon oxidation has been investigated. Several of these systems
      promote the biomimetic dihydroxylation of cyclohexene at low levels, when
      hydrogen peroxide is used as the oxidant; allylic oxidation products are also
      observed. An investigation of ligand stability reveals formation of several
      breakdown products under the conditions of the oxidative turnover reactions.
      These products arise via oxidative decarboxylation, dehydration and deamination
      reactions. Taken together these results indicate that competing mechanisms are at
      play with these systems: biomimetic hydroxylation involving high-valent iron
      species, and allylic oxidation via Fenton chemistry and Haber-Weiss radical
      pathways.

PMID- 22858836
TI  - An immunoreactor-based competitive fluoroimmunoassay for monitoring
      staphylococcal enterotoxin B using bioconjugated quantum dots.
AB  - Extensive research on avian systems has proved hens as an alternate source for
      polyclonal antibody generation necessary for immunosensing applications. Herein,
      we present the immobilization of avian antibody raised against staphylococcal
      enterotoxin B (SEB) and its applicability for a competitive fluoroimmunoassay
      technique. White leghorn hens immunized with SEB generated high affinity
      antibodies with a highest yield of 3.2 mg ml(-1) having affinity constant of
      0.976 * 10(10) M l(-1). A competitive fluoroimmunoassay format was developed
      comprising CdTe(557) as a fluorescence detector for monitoring SEB, a bacterial
      super-antigen. CdTe(557) was bioconjugated to SEB according to the carbodiimide
      protocol and confirmed by absorption spectral analysis. An immunoreactor column
      was designed by immobilizing anti-SEB antibodies and was successfully employed as
      an efficient bio-recognition tool. An immuno-affinity reaction involving
      competitive binding between free SEB and CdTe(557)-bioconjugated SEB for
      immobilized antibody was relied upon to attain assay specificity and sensitivity.
      It was possible to quantify SEB from 1000 to 10 ng based on the integrated
      fluorescence of the SEB-CdTe(557) bioconjugate eluted from the immunoreactor
      column with a limit of detection of 8.15 ng and a regression coefficient R(2) =
      0.9925. Thus, integration of QDs with immuno-affinity reactions revealed the
      versatility of nanoparticles as a potential fluorescence label for bioanalytical
      applications.

PMID- 22858837
TI  - Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial
      cell injury and prevents development of lung cancer.
AB  - Cigarette smoking is the main cause of chronic obstructive pulmonary disease and
      lung cancer. The present study was aimed to explore the chemopreventive effect of
      ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial
      epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the
      intracellular redox balance, and relieved the stimulation of external deleterious
      factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear
      factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer
      development in the model established by A549 cells in nude mice in vivo. For the
      first time, our results indicate that UA could be developed as a potential lung
      cancer chemopreventive agent.

PMID- 22858838
TI  - Protective effects of Chlorella-derived peptide against UVC-induced cytotoxicity
      through inhibition of caspase-3 activity and reduction of the expression of
      phosphorylated FADD and cleaved PARP-1 in skin fibroblasts.
AB  - UVC irradiation induces oxidative stress and leads to cell death through an
      apoptotic pathway. This apoptosis is caused by activation of caspase-3 and
      formation of poly(ADP-ribose) polymerase-1 (PARP-1). In this study, the
      underlying mechanisms of Chlorella derived peptide (CDP) activity against UVC
      induced cytotoxicity were investigated. Human skin fibroblasts were treated with
      CDP, vitamin C, or vitamin E after UVC irradiation for a total energy of 15
      J/cm2. After the UVC exposure, cell proliferation and caspase-3 activity were
      measured at 12, 24, 48, and 72 h later. Expression of phosphorylated FADD and
      cleaved PARP-1 were measured 16 h later. DNA damage (expressed as pyrimidine (6
      4) pyrimidone photoproducts DNA concentration) and fragmentation assay were
      performed 24 h after the UVC exposure. Results showed that UVC irradiation
      induced cytotoxicity in all groups except those treated with CDP. The caspase-3
      activity in CDP-treated cells was inhibited from 12 h onward. Expression of
      phosphorylated FADD and cleaved PARP-1 were also reduced in CDP-treated cells.
      Moreover, UVC-induced DNA damage and fragmentation were also prevented by the CDP
      treatment. This study shows that treatment of CDP provides protective effects
      against UVC-induced cytotoxicity through the inhibition of caspase-3 activity and
      the reduction of phosphorylated FADD and cleaved PARP-1 expression.

PMID- 22858839
TI  - Synthesis and antibacterial activities of amphiphilic neomycin B-based bilipid
      conjugates and fluorinated neomycin B-based lipids.
AB  - Investigating the effect of lipid hydrophobicity on the activity of amphiphilic
      neomycin B conjugates, six polycationic amphiphiles (PAs) were created. Four of
      the new compounds incorporated either palmitic or arachidic di-lipid lysine
      tails, while two had single fluorinated undecanoic acid tails. The basicity of
      half of the compounds was increased through the incorporation of six guanidine
      moieties, in order to assess the effect of base strength on antimicrobial
      activity. A panel of ten bacteria was used for the testing, with seven strains
      obtained from the American Type Culture Collection series and three clinical
      isolates from Canadian Intensive Care Units. When compared to previous results
      with hydrocarbon monolipids the PAs all compounds were found to have reduced
      activity, though the hemolytic activity of the compounds with fluorinated tails
      was sharply reduced, with only a moderate reduction in antimicrobial activity.

PMID- 22858840
TI  - Bioactivities of the genus Combretum (Combretaceae): a review.
AB  - The Combretaceae is a large family of herbs, shrubs and trees, comprising about
      20 genera and 600 species with tropical distribution around the globe and centers
      of diversity in Africa and Asia. Some Combretum species are extensively used in
      traditional medicine against inflammation, infections, diabetes, malaria,
      bleeding, diarrhea and digestive disorders and others as a diuretic. The present
      work is a literature survey of Combretum species that have been evaluated for
      their ability to exert biological activities. A total number of 36 Combretum
      species are discussed with regard to plant parts used, component tested and
      bioassay models. This review is of fundamental importance to promoting studies on
      Combretum species, thereby contributing to the development of new therapeutic
      alternatives that may improve the health of people suffering from various health
      problems.

PMID- 22858841
TI  - Real time anti-Toxoplasma gondii activity of an active fraction of Eurycoma
      longifolia root studied by in situ scanning and transmission electron microscopy.
AB  - The inhibitory effect of active fractions of Eurycoma longifolia (E. longifolia)
      root, namely TAF355 and TAF401, were evaluated against Toxoplasma gondii (T.
      gondii). In our previous study, we demonstrated that T. gondii was susceptible to
      TAF355 and TAF401 with IC50 values of 1.125 ug/mL and 1.375 ug/mL, respectively.
      Transmission (TEM) and scanning electron microscopy (SEM) observations were used
      to study the in situ antiparasitic activity at the IC50 value. Clindamycin was
      used as positive control. SEM examination revealed cell wall alterations with
      formation of invaginations followed by completely collapsed cells compared to the
      normal T. gondii cells in response to the fractions. The main abnormality noted
      via TEM study was decreased cytoplasmic volume, leaving a state of structural
      disorganization within the cell cytoplasm and destruction of its organelles as
      early as 12 h of treatment, which indicated of rapid antiparasitic activity of
      the E. longifolia fractions. The significant antiparasitic activity shown by the
      TAF355 and TAF401 active fractions of E. longifolia suggests their potential as
      new anti-T. gondii agent candidates.

PMID- 22858842
TI  - Cyclization-carbonylation-cyclization coupling reaction of propargyl ureas with
      palladium(II)-bisoxazoline catalyst.
AB  - The cyclization-carbonylation-cyclization coupling reaction (CCC-coupling
      reaction) of propargyl ureas catalyzed by Pd(II)(box) complexes afforded
      symmetrical ketones bearing two 2-amino-2-oxazoline groups in good to moderate
      yields.

PMID- 22858843
TI  - Influences of Dryopteris crassirhizoma extract on the viability, growth and
      virulence properties of Streptococcus mutans.
AB  - Dryopteris crassirhizoma is traditionally used as an herbal remedy for various
      diseases, and has been identified in a previous study as a potential anti-caries
      agent. In this study, the effect of a methanol extract of D. crassirhizoma on the
      viability, growth and virulence properties of Streptococcus mutans, a cariogenic
      dental pathogen, was investigated. In addition, the phytochemical composition of
      the extract was analyzed. The extract showed bactericidal and bacteriostatic
      activity against oral bacteria (MIC and MBC of S. mutans: 62.5 and 250 MUg/mL,
      respectively). At two times the MBC, the extract significantly eliminated S.
      mutans up to 99.9% after 1 h incubation. The extract also dose-dependently
      reduced growth rates of S. mutans at sub-MIC levels. Furthermore, at sub-MIC
      levels, virulence properties (acid production, acid tolerance,
      glucosyltransferase activity and sucrose-dependent adherence) of S. mutans were
      also inhibited in a dose-dependent manner. GC-MS analysis revealed the presence
      of mono and disaccharides (44.9%), fatty acids (12.3%) and sugar alcohols (6.8%)
      in the extract. These data indicate that the extract might be useful for the
      control of dental caries.

PMID- 22858844
TI  - 3-Phenylcoumarins as inhibitors of HIV-1 replication.
AB  - We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their
      anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with
      viral clones carrying the luciferase gene as reporter. Inhibition of HIV
      transcription and Tat function were tested on cells stably transfected with the
      HIV-LTR and Tat protein. Six compounds displayed NF-kappaB inhibition, four
      resulted Tat antagonists and three of them showed both activities. Three
      compounds inhibited HIV replication with IC50 values < 25 uM. The antiviral
      effect of the 4-hydroxycoumarin derivative 19 correlates with its specific
      inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems
      to act through a mechanism unrelated to the molecular targets considered in this
      research.

PMID- 22858845
TI  - Chemical genetics: budding yeast as a platform for drug discovery and mapping of
      genetic pathways.
AB  - The budding yeast Saccharomyces cerevisiae is a widely used model organism, and
      yeast genetic methods are powerful tools for discovery of novel functions of
      genes. Recent advancements in chemical-genetics and chemical-genomics have opened
      new avenues for development of clinically relevant drug treatments. Systematic
      mapping of genetic networks by high-throughput chemical-genetic screens have
      given extensive insight in connections between genetic pathways. Here, I review
      some of the recent developments in chemical-genetic techniques in budding yeast.

PMID- 22858846
TI  - See one. Do one. Teach one. A perfect paradigm for education and training in
      neuroendoscopy.

PMID- 22858847
TI  - Aneurysm rupture--does the weather matter?

PMID- 22858848
TI  - Rotational vertebral artery syndrome.

PMID- 22858849
TI  - Spinal deformity: how to extend the fusion to the sacro-pelvis?

PMID- 22858850
TI  - Expect the unexpected: incidental findings on brain magnetic resonance imaging.

PMID- 22858851
TI  - Perspective--sacral Tarlov cyst: surgical treatment by clipping.

PMID- 22858852
TI  - Rebleeding and its prevention after subarachnoid hemorrhage.

PMID- 22858853
TI  - Transorbital approach to the anterior cranial skull base.

PMID- 22858854
TI  - Quo nunc me vortam?--"What should I do now?".

PMID- 22858855
TI  - Wrong level spine surgery: a perspective.

PMID- 22858856
TI  - Severe ulceration with impaired induction of growth factors and cytokines in
      keratinocytes after trichloroacetic acid application on TRPV1-deficient mice.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a highly polymodal TRP
      channel activated by various stimuli, including capsaicin, heat and acids. TRPV1
      expression can be detected widely but is highest in sensory neurons and its
      activation alerts the body to noxious signals via neurogenic pain. Although TRPV1
      is reportedly localized in the epidermis, it remains unclear how TRPV1 is
      involved in the chemical peeling processes with cytotoxic acids. Therefore, in
      this study, the role of TRPV1 on the effects of trichloroacetic acid (TCA)
      peeling was assessed using TRPV1-deficient mice. Following the confirmation of
      TRPV1 expression in murine keratinocytes with reverse transcription-polymerase
      chain reaction and immunohistochemistry, the effects of TCA on TRPV1-deficient
      mouse skin were compared with those on wild-type mouse skin. Our results
      indicated that TRPV1 expression was not required for TCA-induced DNA damage, as
      shown by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick end labeling, but was indispensable for the TCA-induced production of
      distinct growth factors and cytokines by keratinocytes. Ulceration after TCA
      peeling was actually more severe in the absence of TRPV1, suggesting that the
      TRPV1-mediated epidermal production of growth factors and cytokines affected the
      damaging and healing processes of TCA-peeled skin to induce rejuvenation.

PMID- 22858857
TI  - BRAF mutations in papillary thyroid carcinoma and emerging targeted therapies
      (review).
AB  - Papillary thyroid carcinoma (PTC) is the most common histotype among the thyroid
      cancer types. Although PTC is a curable malignancy, many patients relapse after
      treatment. Thus, there is a need to identify novel factors involved in the
      pathogenesis of PTC that may be used as targets for new therapies. The MAPK
      pathway has been implicated in the pathogenesis of PTC. Therefore, in this
      review, we summarize the role of the BRAF V600E mutation in the development and
      progression of thyroid cancer. The cinical implication of this molecular
      abnormality is also discussed. It is evident that the detection of the BRAF V600E
      mutation is crucial in order to identify novel avenues for thyroid cancer
      treatment.

PMID- 22858858
TI  - Revisiting electronic couplings and incoherent hopping models for electron
      transport in crystalline C60 at ambient temperatures.
AB  - We assess the validity of incoherent hopping models that have previously been
      used to describe electron transport in crystalline C(60) at room temperature. To
      this end we present new density functional theory based calculations of the
      electron transfer parameter defining these models. Specifically, we report
      electronic coupling matrix elements for several ten thousand configurations that
      are thermally accessible to the C(60) molecules through rotational diffusion
      around their lattice sites. We find that the root-mean-square fluctuations of the
      electronic coupling matrix element (11 meV) are almost as large as the average
      value (14 meV) and that the distribution is well approximated by a Gaussian.
      Importantly, due to the small reorganisation energy of the C(60) dimer (~0.1 eV),
      the ET is almost activationless for the majority of configurations. Yet, for a
      small but significant fraction of orientations the coupling is so strong compared
      to reorganisation energy that no charge-localised state exists, a situation that
      is aggravated if zero-point motion of the nuclei is taken into account. The
      present calculations indicate that standard hopping models do not provide a sound
      description of electron transport in C(60), which might be the case for many
      other organics as well, and that approaches are needed that solve the electron
      dynamics directly.

PMID- 22858859
TI  - Imaging in gynecological disease (8): ultrasound characteristics of recurrent
      borderline ovarian tumors.
AB  - OBJECTIVES: To describe the sonographic characteristics of borderline ovarian
      tumor (BOT) recurrence. METHODS: From the databases of five ultrasound centers,
      we retrospectively identified 68 patients with histological diagnosis of
      recurrent BOT who had undergone preoperative ultrasound examination. All
      recurrences were detected during planned follow-up ultrasound examinations.
      Recurrent lesions were described using the terms and definitions of the
      International Ovarian Tumor Analysis (IOTA) group. RESULTS: Sixty-two patients
      had a serous BOT recurrence and six a mucinous BOT recurrence. All patients
      except one were premenopausal, 84% of them being < 40 years old. All but one
      patient were asymptomatic at diagnosis of the recurrence. Fertility-sparing
      surgery of the recurrent tumor was performed in 57/68 (84%) patients. The most
      frequent ultrasound feature of recurrent serous BOT was a unilocular solid cyst
      (49/62, 79%) and almost half of the recurrent serous BOTs (29/62, 47%) had
      multiple papillary projections. In 89% of the recurrent serous BOTs there was at
      least one papillation with irregular surface and in 73% there was at least one
      papillation vascularized at color Doppler examination. Recurrent mucinous BOTs
      appeared mainly as multilocular or multilocular solid cysts (5/6, 83%).
      CONCLUSION: Sonographic features of recurrent BOT resemble those described by
      others for different subtypes of primary BOT.

PMID- 22858860
TI  - Prognostic impact of delta-like ligand 4 and Notch1 in acute myeloid leukemia.
AB  - Notch signaling plays a critical role in embryonic vascular development and tumor
      angiogenesis. The present study was conducted to investigate the prognostic role
      of the angiogenesis-related Notch ligand and the receptor in acute myeloid
      leukemia (AML) and assess whether their expression correlates with that of the
      vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2. Bone marrow
      mononuclear cells from 60 untreated AML patients and 40 healthy controls were
      obtained. Real-time RT-PCR was performed to evaluate the mRNA expression of delta
      like ligand 4 (Dll4), Notch1, VEGF, VEGF receptor (VEGFR)-1, VEGFR-2, Ang-1, Ang
      2 and Tie2. Western blot analysis was used to determine the protein levels of
      Dll4 and Notch1. The results demonstrated that Dll4, Notch1, VEGF, VEGFR-2 and
      Ang-2 expression were significantly higher in untreated AML patients than in the
      controls. Univariate analysis of factors associated with the overall survival
      showed a significantly shorter survival in patients with the unfavorable
      karyotype, higher Dll4 expression, higher Notch1 expression, higher VEGF
      expression or higher Ang-2 expression. Furthermore, multivariate analysis
      revealed that the karyotype and expression levels of Notch1, Dll4, VEGF and Ang-2
      were independent prognostic factors for overall survival. Additionally, the
      prognostic value of Dll4 expression (but not Notch1) was more significant in the
      subgroup consisting of patients with intermediate-risk cytogenetics. Subgroup
      analysis showed that Notch1 and Dll4 expression levels had a prognostic impact on
      patients with high VEGF or Ang-2 levels. Taken together, our data provide
      evidence that the activation of the Notch pathway may indicate an unfavorable
      prognosis in AML. In particular, Dll4 may be a relevant prognostic marker in
      intermediate-risk AML.

PMID- 22858861
TI  - PDMS-glass bonding using grafted polymeric adhesive--alternative process flow for
      compatibility with patterned biological molecules.
AB  - We report a novel modification of silicone elastomer polydimethylsiloxane (PDMS)
      with a polymer graft that allows interfacial bonding between an elastomer and
      glass substrate to be performed without exposure of the substrate to harsh
      treatment conditions, such as oxygen plasma. Organic molecules can thus be
      patterned within microfluidic channels and still remain functional post-bonding.
      In addition, after polymer grafting the PDMS can be stored in a desiccator for at
      least 40 days, and activated upon exposure to acidic buffer for bonding. The
      bonded devices remain fully bonded in excess of 80 psi driving pressure, with no
      signs of compromise to the bond integrity. Finally, we demonstrate the
      compatibility of our method with biological molecules using a proof-of-concept
      DNA sensing device, in which fluorescently-labelled DNA targets are successfully
      captured by a patterned probe in a device sealed using our method, while the
      pattern on a plasma-treated device was completely destroyed. Therefore, this
      method provides a much-needed alternative bonding process for incorporation of
      biological molecules in microfluidic devices.

PMID- 22858862
TI  - Novel Pd(II)-salen complexes showing high in vitro anti-proliferative effects
      against human hepatoma cancer by modulating specific regulatory genes.
AB  - We have reported the synthesis of a novel salen ligand and its mononuclear Pd
      salen complexes derived from 2-{[2-hydroxy-3-{[(E)-(2
      hydroxyphenyl)methylidene]amino}propyl)imino]methyl}phenol. The newly synthesized
      and isolated Pd(II) complexes have been identified and fully characterized by
      various physico-chemical studies viz., elemental analyses, IR, UV-Vis, (1)H,
      (13)C NMR spectroscopy, electron spray ionization mass spectrometry (ESI-MS) and
      TGA/DTA studies. The molecular structure of the salen ligand has been ascertained
      by single-crystal XRD and it is coordinated to Pd(II) ion through two nitrogen
      and two oxygen atoms. The UV-Vis data clearly suggest a square-planar environment
      around both the Pd(II) ions. The DNA binding studies of the synthesized compounds
      has been investigated by electron spectroscopy and fluorescence measurements. The
      results suggest that Pd(II) complexes bind to DNA strongly as compared to the
      free ligand. The free salen ligand and its Pd(II) complexes have also been tested
      against human hepatoma cancer cell line (Huh7) and results manifested exceptional
      anti-proliferative effects of the Pd(II) complexes. The anti-proliferative
      activity of Pd(II) complexes has been modulated by specific regulatory genes.

PMID- 22858863
TI  - A biomimetic mass-flow transducer utilizing all-optofluidic generation of self
      digitized, pulse code-modulated optical pulse trains.
AB  - We present a new mass-flow transducer producing responses in the form of optical
      pulse trains that are encoded with information on the strength and position of
      the stimulus. We implemented the self-digitization and encoding capabilities all
      optofluidically, without involving external electronics, by integrating one
      optical fiber cantilever with multiple polymer optical waveguides on a
      microfluidic platform. The transducer can also be configured to respond only to
      transitional stimuli. These features closely mimic the rate-coding, action
      potential labeling, and rapid adaptation processes observed in biological
      mechanoreceptors and allow multiple transducers to transmit signals over a
      single, shared channel. We fabricated the transducer using polymer-based soft
      lithography techniques. Its characterization confirmed the stimulus strength
      dependent generation of optical pulses and the feasibility of multiplexing 2(n-1)
      to 2(n) transducers using n waveguides.

PMID- 22858864
TI  - Predicting post-event processing in social anxiety disorder following two
      prototypical social situations: state variables and dispositional determinants.
AB  - This study investigated self-reported state (anxiety, physical symptoms,
      cognitions, internally focused attention, safety behaviors, social performance)
      and trait (social anxiety, depressive symptoms, dysfunctional self-consciousness)
      predictors of post-event processing (PEP) subsequent to two social situations
      (interaction, speech) in participants with a primary diagnosis of social anxiety
      disorder (SAD) and healthy controls (HC). The speech triggered significantly more
      intense PEP, especially in SAD. Regardless of the type of social situation, PEP
      was best predicted by situational anxiety and dysfunctional cognitions among the
      state variables. If only trait variables were considered, PEP following both
      situations was accounted for by trait social anxiety. In addition, dysfunctional
      self-consciousness contributed to PEP-speech. If state and trait variables were
      jointly considered, for both situations, situational anxiety and dysfunctional
      cognitions were confirmed as the most powerful PEP predictors above and beyond
      trait social anxiety (interaction) and dysfunctional self-consciousness (speech).
      Hence, PEP as assessed on the day after a social situation seems to be mainly
      determined by state variables. Trait social anxiety and dysfunctional self
      consciousness also significantly contribute to PEP depending on the type of
      social situation. The present findings support dysfunctional cognitions as a core
      cognitive mechanism for the maintenance of SAD. Implications for treatment are
      discussed.

PMID- 22858865
TI  - A mixture of amino acids and other small molecules present in the serum
      suppresses the growth of murine and human tumors in vivo.
AB  - Previously we have hypothesized that the small molecules which are selectively
      accumulated in cancer cells might participate in a non-immunological antitumor
      surveillance mechanism. We demonstrated earlier that a mixture of experimentally
      selected substances ("active mixture", AM: L-arginine, L-histidine, L-methionine,
      L-phenylalanine, L-tyrosine, L-tryptophan, L-ascorbate, D-biotin, pyridoxine,
      riboflavin, adenine, L(-)malate) possesses a selective toxic effect in vitro on a
      variety of tumor cell lines, and we have shown that the AM selectively induces
      apoptosis of cancer cells in vitro. To explore the in vivo significance of our
      earlier findings we examined the antitumor effect of AM in Colon 26 murine
      colorectal adenocarcinoma, B16 murine melanoma, MXT murine mammary carcinoma,
      S180 murine sarcoma, P388 murine lymphoid leukemia, HL-60 human promyeloid
      leukemia, PC-3 human prostate carcinoma, and HT-29 human colon carcinoma tumor
      models. Treatment of tumor bearing mice with AM inhibited the growth of the
      tumors investigated, with an inhibitory effect ranging from 40 to 69%. The AM had
      a comparable antitumor effect with 5-fluorouracil and cisplatin in the Colon-26
      tumor model, and combined treatment with AM and 5-fluorouracil or cisplatin
      resulted in an enhanced tumor growth inhibitory effect. The AM induced apoptosis
      through the mitochondrial pathway and induced G1 arrest in PC-3 cells and
      increased the number of apoptotic cells in PC-3 xenografts. These findings
      suggest that the AM might offer an interesting perspective in the treatment of
      cancer and in combination with other treatments may offer hope for a more
      effective cancer therapy.

PMID- 22858866
TI  - Structural and functional studies of the phage Sf6 terminase small subunit reveal
      a DNA-spooling device facilitated by structural plasticity.
AB  - In many DNA viruses, genome packaging is initiated by the small subunit of the
      packaging terminase, which specifically binds to the packaging signal on viral
      DNA and directs assembly of the terminase holoenzyme. We have experimentally
      mapped the DNA-interacting region on Shigella virus Sf6 terminase small subunit
      gp1, which occupies extended surface areas encircling the gp1 octamer, indicating
      that DNA wraps around gp1 through extensive contacts. High-resolution structures
      reveal large-scale motions of the gp1 DNA-binding domain mediated by the curved
      helix formed by residues 54-81 and an intermolecular salt bridge formed by
      residues Arg67 and Glu73, indicating remarkable structural plasticity underlying
      multivalent, pleomorphic gp1:DNA interactions. These results provide spatial
      restraints for protein:DNA interactions, which enable construction of a three
      dimensional pseudo-atomic model for a DNA-packaging initiation complex assembled
      from the terminase small subunit and the packaging region on viral DNA. Our
      results suggest that gp1 functions as a DNA-spooling device, which may transform
      DNA into a specific architecture appropriate for interaction with and cleavage by
      the terminase large subunit prior to DNA translocation into viral procapsid. This
      may represent a common mechanism for the initiation step of DNA packaging in
      tailed double-stranded DNA bacterial viruses.

PMID- 22858868
TI  - Optimizing membrane protein overexpression in the Escherichia coli strain
      Lemo21(DE3).
AB  - Escherichia coli BL21(DE3) is widely used to overexpress proteins. In this
      overexpression host, the gene encoding the target protein is located on a plasmid
      and is under control of the T7 promoter, which is recognized exclusively by the
      T7 RNA polymerase (RNAP). The T7 RNAP gene is localized on the chromosome, and
      its expression is governed by the non-titratable, IPTG-inducible lacUV5 promoter.
      Recently, we constructed the Lemo21(DE3) strain, which allows improved control
      over the expression of genes from the T7 promoter. Lemo21(DE3) is a BL21(DE3)
      strain equipped with a plasmid harboring the gene encoding T7 lysozyme, an
      inhibitor of the T7 RNAP, under control of the exceptionally well-titratable
      rhamnose promoter. The overexpression yields of a large collection of membrane
      proteins in Lemo21(DE3) at different concentrations of rhamnose indicated that
      this strain may be very suitable for optimizing the production of membrane
      proteins. However, insight in the mechanism by which optimized expression yields
      are achieved in Lemo21(DE3) is lacking. Furthermore, whether the overexpressed
      proteins are suitable for functional and structural studies remains to be tested.
      Here, we show that in Lemo21(DE3), (i) the modulation of the activity of the T7
      RNAP by the T7 lysozyme is key to optimizing the ratio of membrane proteins
      properly inserted in the cytoplasmic membrane to non-inserted proteins; (ii)
      maximizing the yields of membrane proteins is accompanied by reduction of the
      adverse effects of membrane protein overexpression, resulting in stable
      overexpression; and (iii) produced membrane proteins can be used for functional
      and structural studies.

PMID- 22858869
TI  - Multidisciplinary rehabilitation in women following breast cancer treatment: a
      randomized controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of a multidisciplinary ambulatory
      rehabilitation programme for women following definitive breast cancer treatment
      in an Australian community cohort. METHODS: Eighty-five women in the community
      randomized to a treatment group (n = 43) for individualized high-intensity
      programme, or a control group (n = 42) comprising usual activity. The primary
      outcome Depression Anxiety Stress Scale (DASS) scale measured restriction in
      participation. Secondary measures included Perceived Impact Problem Profile
      (PIPP) and Cancer Rehabilitation Evaluation System Short-Form (CARES-SF); and
      Functional Independence Measure (FIM) motor subscale for activity limitation.
      Assessments were at baseline and 4 months. RESULTS: Intention-to-treat analysis
      of data showed a significant difference between both groups in DASS Depression
      scores (p = 0.006) (moderate effect size, r > 0.3), PIPP Mobility (p = 0.05) and
      Participation (p = 0.04) scales, and CARES-SF Global score (p = 0.02) (small
      effect size, r < 0.3). The treatment group, compared with control group, showed
      significant improvement in the DASS Depression scores: 22/42 (52.4%) vs 12/37
      (32.4%) (p = 0.02). No difference between groups was noted in the FIM scale.
      CONCLUSION: Rehabilitation can benefit participation in breast cancer survivors.
      Evidence for specific rehabilitation interventions is needed. Integrated cancer
      programmes allow opportunities to evaluate patients in various settings, but
      require outcome research to develop service models for survivorship issues.

PMID- 22858867
TI  - Structural interactions between lipids, water and S1-S4 voltage-sensing domains.
AB  - Membrane proteins serve crucial signaling and transport functions, yet relatively
      little is known about their structures in membrane environments or how lipids
      interact with these proteins. For voltage-activated ion channels, X-ray
      structures suggest that the mobile voltage-sensing S4 helix would be exposed to
      the membrane, and functional studies reveal that lipid modification can
      profoundly alter channel activity. Here, we use solid-state NMR to investigate
      structural interactions of lipids and water with S1-S4 voltage-sensing domains
      and to explore whether lipids influence the structure of the protein. Our results
      demonstrate that S1-S4 domains exhibit extensive interactions with lipids and
      that these domains are heavily hydrated when embedded in a membrane. We also find
      evidence for preferential interactions of anionic lipids with S1-S4 domains and
      that these interactions have lifetimes on the timescale of <= 10(-3)s. Arg
      residues within S1-S4 domains are well hydrated and are positioned in close
      proximity to lipids, exhibiting local interactions with both lipid headgroups and
      acyl chains. Comparative studies with a positively charged lipid lacking a
      phosphodiester group reveal that this lipid modification has only modest effects
      on the structure and hydration of S1-S4 domains. Taken together, our results
      demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close
      proximity to the hydrophobic interior of the membrane yet are well hydrated, a
      requirement for carrying charge and driving protein motions in response to
      changes in membrane voltage.

PMID- 22858870
TI  - A prototype continuous-flow liquid-liquid extraction system using open-source
      technology.
AB  - A prototype continuous-flow liquid-liquid extraction system is reported. By
      harnessing several open-source software libraries, a computer control script was
      written using the Python programming language. Using a 'computer-vision'
      approach, this allowed the computer to monitor the interface level between the
      organic and aqueous phases using a simple webcam setup and (by dynamically
      controlling pump flow rate) to keep this interface within defined limits. The
      system enabled the efficient 'inline' extraction of excess reagent in hydrazone
      formations, dithiane formations and epoxidations. The initial results of
      dispersion measurement are also presented.

PMID- 22858871
TI  - Fluconazole-induced fixed drug eruption imitating herpes labialis with erythema
      multiforme.

PMID- 22858872
TI  - Amorphization of nanocrystalline monoclinic ZrO2 by swift heavy ion irradiation.
AB  - Bulk ZrO(2) polymorphs generally have an extremely high amorphization tolerance
      upon low energy ion and swift heavy ion irradiation in which ballistic
      interaction and ionization radiation dominate the ion-solid interaction,
      respectively. However, under very high-energy irradiation by 1.33 GeV U-238,
      nanocrystalline (40-50 nm) monoclinic ZrO(2) can be amorphized. A computational
      simulation based on a thermal spike model reveals that the strong ionizing
      radiation from swift heavy ions with a very high electronic energy loss of 52.2
      keV nm(-1) can induce transient zones with temperatures well above the ZrO(2)
      melting point. The extreme electronic energy loss, coupled with the high energy
      state of the nanostructured materials and a high thermal confinement due to the
      less effective heat transport within the transient hot zone, may eventually be
      responsible for the ionizing radiation-induced amorphization without transforming
      to the tetragonal polymorph. The amorphization of nanocrystalline zirconia was
      also confirmed by 1.69 GeV Au ion irradiation with the electronic energy loss of
      40 keV nm(-1). These results suggest that highly radiation tolerant materials in
      bulk forms, such as ZrO(2), may be radiation sensitive with the reduced length
      scale down to the nano-metered regime upon irradiation above a threshold value of
      electronic energy loss.

PMID- 22858873
TI  - Text-speak processing impairs tactile location.
AB  - Dual task experiments have highlighted that driving while having a conversation
      on a cell phone can have negative impacts on driving (Strayer & Drews, 2007). It
      has also been noted that this negative impact is greater when reading a text
      message (Lee, 2007). Commonly used in text-messaging are shortening devices
      collectively known as text-speak (e.g.,Ys I wll ttyl 2nite, Yes I will talk to
      you later tonight). To the authors' knowledge, there has been no investigation
      into the potential negative impacts of reading text-speak on concurrent
      performance on other tasks. Forty participants read a correctly spelled story and
      a story presented in text-speak while concurrently monitoring for a vibration
      around their waist. Slower reaction times and fewer correct vibration detections
      occurred while reading text-speak than while reading a correctly spelled story.
      The results suggest that reading text-speak imposes greater cognitive load than
      reading correctly spelled text. These findings suggest that the negative impact
      of text messaging on driving may be compounded by the messages being in text
      speak, instead of orthographically correct text.

PMID- 22858874
TI  - Causal conditionals and counterfactuals.
AB  - Causal counterfactuals e.g., 'if the ignition key had been turned then the car
      would have started' and causal conditionals e.g., 'if the ignition key was turned
      then the car started' are understood by thinking about multiple possibilities of
      different sorts, as shown in six experiments using converging evidence from three
      different types of measures. Experiments 1a and 1b showed that conditionals that
      comprise enabling causes, e.g., 'if the ignition key was turned then the car
      started' primed people to read quickly conjunctions referring to the possibility
      of the enabler occurring without the outcome, e.g., 'the ignition key was turned
      and the car did not start'. Experiments 2a and 2b showed that people paraphrased
      causal conditionals by using causal or temporal connectives (because, when),
      whereas they paraphrased causal counterfactuals by using subjunctive
      constructions (had...would have). Experiments 3a and 3b showed that people made
      different inferences from counterfactuals presented with enabling conditions
      compared to none. The implications of the results for alternative theories of
      conditionals are discussed.

PMID- 22858875
TI  - Boundaries of reciprocity: incompleteness of information undermines cooperation.
AB  - Past research has revealed that people have a strong tendency to respond to
      others' cooperative behavior with cooperation and to others' noncooperative
      behavior with noncooperation. Yet it is unclear whether or not this tendency
      still holds when people have only incomplete information about their interaction
      partner's past behavior. To address this question, we designed a new paradigm - a
      coin allocation paradigm - in which participants were provided with incomplete
      information about another person's degree of cooperative behavior (i.e., coin
      allocations to the participant). Consistent with our hypotheses, two experiments
      revealed that incompleteness of information undermines both expectations about
      another person's cooperation as well as one's own cooperation. Moreover,
      complementary analyses indicated that the detrimental effects of incompleteness
      of information on cooperation were mediated by expectations of other's
      cooperation. We suggest that a relatively strong belief in self-interest serves
      to fill in the blanks when information is incomplete, which undermines
      expectations of other's cooperation as well as one's own cooperative behavior.

PMID- 22858876
TI  - Subliminal priming and effects of hand dominance.
AB  - In the masked priming paradigm, motor responses to targets are influenced by
      previously presented subliminal primes, and are guided by facilitatory and
      inhibitory mechanisms that depend on prime-target compatibility/duration. In this
      study, we evaluate subliminal-driven priming in right- and left-handers during
      unimanual as well as bimanual tasks. The data from the unimanual tasks confirmed
      that prime-target compatibility affects performance as a function of prime-target
      duration. In a bimanual setting, the preferred hand benefitted from facilitation
      in both handedness groups whereas the non-preferred hand showed a positive
      priming effect only in left-handers. This denotes that left-handers are more
      susceptible to response activation of either hand. In addition, inhibitory
      priming had a stronger effect on the non-preferred than preferred hand,
      independent of handedness group. Overall, the findings suggest that subliminal
      driven mechanisms that assist adaptive motor behavior are sensitive not only to
      extrinsic (task-related) factors such as prime-target compatibility but also to
      intrinsic (performer-related) factors such as hand dominance. The data further
      provide support for handedness-specific effects in motor functions and underline
      a significant role of hand dominance in the control of bimanual actions.

PMID- 22858877
TI  - Lung ultrasound in the ICU: from diagnostic instrument to respiratory monitoring
      tool.
AB  - Imaging has greatly contributed to the understanding of lung disease in the
      critically ill and currently serves as a tool to diagnose lung pathology, monitor
      its course, and guide clinical management. Lung ultrasound is a real-time imaging
      modality that is simple, non-invasive, potentially ubiquitous, and free of
      ionizing radiation. Its increasing popularity and supporting research data
      substantiate its role as an emerging technique for bedside chest imaging in
      critical care. Furthermore, the International Consensus Conference on Lung
      ultrasound (ICC-LUS) promoted by the World Interactive Network Focused on
      Critical UltraSound (WINFOCUS) recently standardized the nomenclature and
      technique for lung ultrasound, and provided recommendations supporting its use in
      clinical practice. While the utility of lung ultrasound in the emergency setting
      is unquestioned, its potential role in the more complex and resource-rich
      intensive care environment is still under investigation. The purpose of this
      paper was to describe current and potential uses of lung ultrasound in the
      specific setting of adult intensive care, with an emphasis on respiratory
      monitoring, and to provide a framework for the practical application of this tool
      at the bedside.

PMID- 22858878
TI  - Coagulation assessment in normal pregnancy: thrombelastography with citrated non
      activated samples.
AB  - BACKGROUND: Thrombelastography (TEG) provides an effective and convenient means
      of whole blood coagulation monitoring. TEG evaluates the elastic properties of
      whole blood and provides a global assessment of hemostatic function. Previous
      studies performed TEG on native blood sample, but no data are available with
      citrated samples in healthy pregnant women at term. The aim of this study was to
      investigate the effect of pregnancy on coagulation assessed by TEG and establish
      normal ranges of TEG values in pregnant women at term comparing them with healthy
      non pregnant young women. METHODS: We enrolled pregnant women at term undergoing
      elective cesarean section or labour induction (PREG group) and healthy non
      pregnant women (CTRL group). Women with fever or inflammatory syndrome, defined
      as C-reactive protein (CRP) >5 mg/L and with a platelet count <150.000/mm(3) have
      been excluded. For each women hemochrome and standard coagulation test were
      assessed. At the same time we performed a thrombelastographic test with Hemoscope
      TEG((r)) after sample recalcification without using any activator. RESULTS: One
      hundred thirty patients were studied, 65 for each group. There were no
      differences between groups regarding demographic data. Hemoglobin, platelet
      count, International Normalized Ratio and Activated Partial Thromboplastin Time
      Ratio were lower and fibrinogen was higher in PREG group. All TEG parameters
      resulted as being significantly different between the groups with a
      hypercoagulable pattern in PREG group compared to CTRL group. CONCLUSION: The
      main findings of this study confirm the hypercoagulability status of pregnant
      women at term. This coagulation pattern is well represented by
      thrombelastographic trace obtained by recalcified citrate blood sample.

PMID- 22858882
TI  - Limits and pitfalls of haemodynamic monitoring systems in liver transplantation
      surgery.
AB  - Cardiac output (CO) and other hemodynamic variables measured during liver
      transplantation are often obtained by pulmonary artery catheter (PAC) and in many
      centers by the transthoracic thermodilution method and/or intraoperative
      transesophageal echocardiography (TEE). Newer non-invasive technology, such as
      the PiCCO((r)) system, the LiDCO((r)) Plus monitor, and the FloTrac/Vigileo((r)),
      have been proposed as more reflective of ongoing hemodynamic response to
      intraoperative manoeuvres. In contrast to the standard "semicontinuous"
      thermodilution method, which gives information over a set period of time, the new
      monitoring systems use a different time period or measure over a running several
      beat average. It has been stated that algorithms based on arterial pulse contour
      analysis can potentially facilitate rapid diagnosis and prompt therapeutic
      interventions. However, as the use of these technologies has spread, so has the
      understanding of their limitations. This has led to an increased scepticism among
      the previously enthusiastic "pioneering" practitioners. Given the poor agreement
      reported in various studies on liver transplant surgery between PAC and the new
      "calibrated" and "uncalibrated"-derived measurements, multicenter trials aiming
      at evaluating the performance of the non-invasive methods in different
      hemodynamic conditions and dedicated monitoring-driven treatment protocols are
      necessary.

PMID- 22858883
TI  - Linezolid use in ventilator-associated pneumonia: look at the body weight of your
      patient!

PMID- 22858884
TI  - Measuring dead-space in acute lung injury.
AB  - Several recent studies have advanced our understanding of dead-space ventilation
      in patients with acute lung injury/acute respiratory distress syndrome
      (ALI/ARDS). They have demonstrated the utility of measuring physiologic dead
      space-to-tidal volume ratio (VD/VT) and related variables in assessing outcomes
      as well as therapeutic interventions. These studies have included the evaluation
      of mortality risk, pulmonary perfusion, as well as the effectiveness of drug
      therapy, prone positioning, positive end-expiratory pressure (PEEP) titration,
      and inspiratory pattern in improving gas exchange. In patients with ALI/ARDS
      managed with lung-protective ventilation a significant relationship between
      elevated VD/VT and increased mortality continues to be reported in both early and
      intermediate phases of ALI/ARDS. Some clinical evidence now supports the
      suggestion that elevated VD/VT in part reflects the severity of pulmonary
      vascular endothelial damage. Monitoring VD/VT also appears useful in assessing
      alveolar recruitment when titrating PEEP and may be a particularly expedient
      method for assessing the effectiveness of prone positioning. It also has revealed
      how subtle manipulations of inspiratory time and pattern can improve CO(2)
      excretion. Much of this has been accomplished using volumetric capnography. This
      allows for more sophisticated measurements of pulmonary gas exchange function
      including: alveolar VD/VT, the volume of CO(2) excretion and the slope of the
      alveolar plateau which reflects ventilation: perfusion heterogeneity. Many of
      these measurements now can be made non-invasively which should only increase the
      research and clinical utility of volumetric capnography in studying and managing
      patients with ALI/ARDS.

PMID- 22858886
TI  - Simulation and non-technical skills: the way is correct but more accurate
      researches are mandatory.

PMID- 22858888
TI  - Impact of ovulation and implantation timing on first-trimester crown-rump length
      and gestational age.
AB  - OBJECTIVE: To determine the impact of ovulation and implantation timing on first
      trimester crown-rump length (CRL) and the derived gestational age (GA). METHOD:
      One hundred and forty-three women who were trying to conceive were recruited
      prospectively. The timing of ovulation and implantation and the ovulation to
      implantation (O-I) interval were established in 101 pregnancies using home
      urinary tests for luteinizing hormone and human chorionic gonadotropin. In 71
      ongoing pregnancies, GA determined by measurement of fetal CRL at 10-14 weeks'
      gestation was compared with GA based on ovulation and implantation day. First
      trimester growth was determined by serial ultrasound scans at 6-7, 8-9 and 10-14
      weeks. RESULTS: The median ovulation and implantation days were 16 and 27,
      respectively, with an O-I interval of 11 days. GA estimated from CRL at 10-14
      weeks was on average 1.3 days greater than that derived from ovulation timing.
      CRL Z-score was inversely related to O-I interval (rho= -0.431, P=0.0009). There
      was no significant relationship between CRL growth rate and the difference
      between observed CRL and expected CRL based on GA from last menstrual period
      (rho=0.224, P=0.08). CONCLUSIONS: Early implantation leads to a larger CRL and
      late implantation to a smaller CRL at 10-14 weeks, independent of CRL growth
      rate. Implantation timing is a major determinant of fetal size at 10-14 weeks and
      largely explains the variation in estimates of GA in the first trimester derived
      from embryonic or fetal CRL.

PMID- 22858889
TI  - Effect of delivery room temperature on the admission temperature of premature
      infants: a randomized controlled trial.
AB  - OBJECTIVE: To determine if increasing delivery room temperature to that
      recommended by the World Health Organization results in increased admission
      temperatures of preterm infants. STUDY DESIGN: Admission rectal temperatures of
      newborns <=32 weeks gestation delivered in rooms with temperature set at 24 to 26
      degrees C were compared with those of similar newborns delivered in rooms with
      temperature set at 20 to 23  degrees C. RESULT: Premature newborns delivered in
      rooms with mean temperature 25.1+/-0.6  degrees C (n=43), compared with those
      delivered in rooms with mean temperature 22.5+/-0.6  degrees C (n=48), had a
      lower incidence (34.9% vs 68.8%, P<0.01) of admission rectal temperature <36 
      degrees C and higher admission rectal temperatures (36.0+/-0.9  degrees C vs
      35.5+/-0.8  degrees C, P<0.01). This difference persisted after adjustment for
      birth weight and 5 min Apgar score. CONCLUSION: Increasing delivery room
      temperatures to that recommended by the World Health Organization decreases cold
      stress in premature newborns.

PMID- 22858890
TI  - Response times for emergency cesarean delivery: use of simulation drills to
      assess and improve obstetric team performance.
AB  - OBJECTIVE: We documented time to key milestones and determined reasons for
      transport-related delays during simulated emergency cesarean. STUDY DESIGN:
      Prospective, observational investigation of delivery of care processes by
      multidisciplinary teams of obstetric providers on the labor and delivery unit at
      Lucile Packard Children's Hospital, Stanford, CA, USA, during 14 simulated
      uterine rupture scenarios. The primary outcome measure was the total time from
      recognition of the emergency (time zero) to that of surgical incision. RESULT:
      The median (interquartile range) from time zero until incision was 9 min 27 s
      (8:55 to 10:27 min:s). CONCLUSION: In this series of emergency cesarean drills,
      our teams required approximately nine and a half minutes to move from the labor
      room to the nearby operating room (OR) and make the surgical incision. Multiple
      barriers to efficient transport were identified. This study demonstrates the
      utility of simulation to identify and correct institution-specific barriers that
      delay transport to the OR and initiation of emergency cesarean delivery.

PMID- 22858891
TI  - Ligand-based solid solution approach to stabilisation of sulphonic acid groups in
      porous coordination polymer Zr6O4(OH)4(BDC)6 (UiO-66).
AB  - By adopting a ligand-based solid solution approach, the sulphonic acid functional
      group can be successfully incorporated into a porous coordination polymer with
      UiO-66 structure type. Zr(6)O(4)(OH)(4)(BDC-SO(3)H)(1.1)(BDC)(4.9) possesses
      enhanced heat of adsorption for carbon dioxide and acetone compared to
      Zr(6)O(4)(OH)(4)(BDC)(6).

PMID- 22858892
TI  - The mobilization, recruitment and contribution of bone marrow-derived endothelial
      progenitor cells to the tumor neovascularization occur at an early stage and
      throughout the entire process of hepatocellular carcinoma growth.
AB  - Obvious neovascularization is a key feature of hepatocellular carcinoma (HCC) and
      the status of neovascularization in HCC is closely correlated with the tumor
      growth and patient prognosis. The actual effect of current antivascular treatment
      including embolization to HCC is not satisfactory. Compensatory angiogenesis is
      one of the primary causes responsible for failure of antiangiogenic therapy. Bone
      marrow-derived endothelial progenitor cells (BM-EPCs) are considered as important
      building blocks for adult neovascularization. However, the role of mobilized BM
      EPCs in HCC remains unknown. In this study, GFP+-BM orthotropic HCC mice were
      established to investigate whether BM-EPCs are involved in HCC-induced
      neovascularization. We found that a large number of BM-EPCs were mobilized into
      the circulation with the development of HCC, recruited into the HCC region and
      incorporated into the vascular endothelium directly by differentiation into
      vascular endothelial cells, including sinus, capillary vessels and great vessels.
      Dynamic observation revealed that the mobilization and the incorporation of BM
      EPCs into different types of vessels were present in early phases and throughout
      the whole process of HCC growth. The proportion of BM-EPCs in vessels increased
      gradually, from 17 to 21% with tumor growth. Moreover, injected GFP+-EPCs also
      specifically homed to tumor tissue and incorporated into tumor vessels directly.
      In this initial study, we demonstrated that BM-EPCs play a prominent role in HCC
      neovascularization. Blockade of BM-EPC-mediated vasculogenesis may improve the
      efficacy of current anti-vascularization therapy for patients with HCC.

PMID- 22858893
TI  - Effectiveness of cognitive-behavioral trauma treatment for incarcerated women
      with mental illnesses and substance abuse disorders.
AB  - An open trial design was used to examine the implementation and effectiveness of
      a cognitive-behavioral intervention (Seeking Safety) for comorbid post-traumatic
      stress disorder (PTSD) and substance use disorder (SUD) for incarcerated women
      with Axis I mental disorders who self-referred for specialty trauma treatment.
      The study sample was female inmates aged 18 and old who were primarily minority,
      had experienced childhood-based trauma, committed violent crimes, had a serious
      mental illness, and resided in maximum, medium, and minimum compounds of a
      women's prison. A total of 74 women completed the group intervention, with the
      average attending 23 of the 28 sessions (82%). Implementation feasibility was
      demonstrated by the ability to recruit, screen, assign, and retain participation.
      Effectiveness was supported by changes pre-post intervention on the PTSD
      Checklist (ES=0.56) and Global Severity Index (ES=0.47). Of the 19 completers
      with PCL scores of 50 or higher pre-intervention, 16 (84%) had scores below 50,
      the "cut score" consistent with or supportive of a PTSD diagnosis. Three-quarters
      or more of participants reported that Seeking Safety was helpful in each of the
      following areas: overall, for traumatic stress symptoms, for substance use, to
      focus on safety, and to learn safe coping skills. Future directions include the
      need for larger scale randomized controlled trials in medium or maximum security
      prisons and fidelity evaluations of non-research dissemination efforts.

PMID- 22858894
TI  - Initial experience in ablation of typical atrial flutter using a novel three
      dimensional catheter tracking system.
AB  - AIMS: Three-dimensional (3D) mapping has been established for clinical routine in
      an interventional electrophysiology (EP). Recently, a novel sensor-based 3D
      catheter tracking system has been introduced integrating 3D non-fluoroscopic
      catheter navigation into the environment of pre-recorded 2D fluoroscopy
      [MediGuideTM Technology (MG)]. We are reporting on the first clinical experience
      for ablation of typical atrial flutter. First we aimed to demonstrate safety and
      feasibility of this new technique. Secondly, procedural aspects such as
      effectiveness, procedure, and fluoroscopy time should be evaluated. METHODS AND
      RESULTS: Ten consecutive patients (100% male, age 68 +/- 8 years) were ablated
      using MG technology. Two steerable diagnostic EP catheters (MediGuide Enabled
      LivewireTM Catheter, SJM) were used for coronary sinus cannulation and anatomical
      cavo-tricuspidal isthmus (CTI) reconstruction within the EnSite NavXTM System
      (NavX). Ablation was performed with a conventional 8 mm tip ablation catheter
      (IBI, SJM). In all 10 patients both sensor-equipped MG catheters could be tracked
      non-fluoroscopically. Successful anatomical CTI reconstruction was performed and
      complete isthmus block was documented after the ablation. Total procedure
      duration was comparable with conventional procedures (55 +/- 8 min). Usage of the
      MG tracking system resulted in a fluoroscopy time of 2.5 +/- 2 min. No adverse
      events occurred during the procedures. CONCLUSIONS: For the first clinical
      application of the MG technology in an interventional electrophysiology we found
      a stable system enabling excellent 3D orientation for spatial catheter
      positioning on the basis of underlying pre-recorded cine loops. Clinically, the
      MG technology allowed successful procedures with short fluoroscopy times, even
      though a sensor-equipped ablation catheter was not yet available for use in the
      study.

PMID- 22858895
TI  - Dermoscopic features of reticulated acanthoma (superficial epithelioma) with
      sebaceous differentiation.

PMID- 22858896
TI  - Familial aggregation of malignant mesothelioma in former workers and residents of
      Wittenoom, Western Australia.
AB  - Clustering of cases of malignant mesothelioma within families has often been
      observed, but disentangling genetic and exposure effects has not been done.
      Former workers and residents exposed to crocidolite at Wittenoom, Western
      Australia, where many families shared exposure to asbestos, have had high rates
      of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma
      in relatives, after allowance for common exposure to crocidolite. More than
      11,000 former asbestos workers and residents from Wittenoom have been followed up
      in cancer and death registries. Levels of exposure for all members of the
      Wittenoom cohorts have been estimated previously. Relationships between family
      members of all mesothelioma cases were established from questionnaires, birth and
      death certificates. Expected numbers of cases of mesothelioma were estimated by
      fitting a Weibull survival model to all data, based on time from first asbestos
      exposure, duration and intensity of exposure and age. For each family group, the
      earliest case was considered the index case. Predicted risk was estimated for
      each subject from the time of diagnosis of the index case. Familial risk ratios
      were estimated by dividing observed cases by the sum of risks of all same degree
      relatives of index cases. There were 369 family groups with at least one case of
      mesothelioma and a further 25 cases of mesothelioma among relatives in the same
      families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95%
      confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an
      important, but not large, genetic component in mesothelioma, similar to many
      other cancers.

PMID- 22858897
TI  - The dimensionality of PTSD symptoms and their relationship to health-related
      quality of life in Chinese earthquake survivors.
AB  - The current study investigated the latent structure of PTSD symptoms with a
      sample of 326 Chinese survivors who lost their children during a deadly
      earthquake. The results of confirmatory factor analysis indicated that a five
      factor intercorrelated model comprised of intrusion, avoidance, emotional
      numbing, dysphoric arousal, and anxiety arousal provided significant better fit
      than both the four-factor numbing model of King, Leskin, King, and Weathers
      (1998) and the four-factor dysphoria model of Simms, Watson, and Doebbeling
      (2002). Further analyses with structural equation modeling showed that the PTSD
      factors were differentially associated with external measures of psychosocial and
      physical health-related quality of life. The findings provide further empirical
      support for the novel five-factor PTSD model, and carry implications for
      conceptualizing and assessing PTSD for the upcoming DSM-5.

PMID- 22858898
TI  - Anxiety and its treatment: promoting science-based practice.
AB  - In this article we analyze ways that psychological science can inform the
      treatment of anxiety disorders. We focus on experimental psychopathology research
      to describe the structure of anxiety and the functions of danger, safety,
      predictability and controllability in contributing to disorder. We then address
      science-based practice in terms of principles of change and the benefits from the
      self-corrective nature of science, contrasting this form of practice with
      treatments that are not grounded in basic learning theory. Models for
      dissemination and implementation of science-based practices are described and
      related to practitioner attitudes regarding scientific evidence. Finally, we
      consider practice implications when treatments are, and are not, based on the
      informative role of clinical psychological science.

PMID- 22858899
TI  - Psychometric properties of the Spence Children's Anxiety Scale (SCAS) in Mainland
      Chinese children and adolescents.
AB  - This study examined the psychometric properties of the Spence Children's Anxiety
      Scale (SCAS) in a Mainland Chinese community sample. The 38-item Chinese version
      of SCAS was administered to 1878 children and adolescents. Multiple group
      confirmatory factor analyses supported a common 6-factor model of SCAS for
      children and adolescents, and for boys and girls. The internal consistency and
      test-retest reliability of SCAS were satisfactory. Convergent and divergent
      validity of SCAS were supported by significant correlations with a measure of
      anxiety to a greater extent than with a measure of depression. Adolescents
      reported higher anxiety levels than children, and girls reported higher anxiety
      levels than boys. Compared to other studies, anxiety symptoms of Chinese children
      were found at a moderate level, but anxiety symptoms of Chinese adolescents were
      found at a high level. Our findings suggest that the SCAS is suitable for
      assessing anxiety symptoms in Mainland Chinese children and adolescents.

PMID- 22858900
TI  - The relationships of child and parent factors with children's anxiety symptoms:
      parental anxious rearing as a mediator.
AB  - A considerable body of research has identified various child and parent factors
      that contribute to and maintain anxiety symptoms in children. Yet relatively few
      studies have examined child factors (including threat-based cognitive bias,
      neuroticism, gender, puberty and age) as well as parent factors (including
      maternal anxiety and child-rearing style) in association with child anxiety
      symptoms, and the extent to which these factors serve as unique predictors of
      child anxiety. Moreover, research is lacking on whether parent factors such as
      child-rearing style, which is often targeted in early intervention and treatment
      programs, might mediate the association between child factors such as
      neuroticism, and child anxiety symptoms. In a sample of 85 children between 7 and
      12 years of age with varying levels of anxiety, including those with diagnosed
      anxiety disorders, results showed that children were more anxious when they were
      reported to be more advanced in pubertal status by their parents, when they had a
      tendency to interpret more threat in ambiguous situations, and when they self
      reported more neuroticism. Regarding parent factors, maternal self-reported trait
      anxiety and children's perceptions of their mother as having an anxious child
      rearing style were associated with higher levels of child anxiety. Moreover, when
      these correlates of child anxiety were examined in a multivariate model to
      identify those that had direct as well as indirect associations via maternal
      anxious child-rearing style, child neuroticism remained as a significant and
      unique predictor of child anxiety that was also mediated by maternal anxious
      rearing. Child neuroticism also mediated the relationship between child pubertal
      stage and anxiety symptoms. Results are discussed in terms of relevant theory and
      empirical evidence regarding the roles of both child and parent factors in the
      development of child anxiety.

PMID- 22858901
TI  - The epidemiology of obsessive--compulsive disorder in Spanish school children.
AB  - We aimed to assess the prevalence (at three levels of severity) and other
      epidemiological data of OCD in a sample of 1,514 Spanish non-referred children.
      The estimated prevalence was 1.8% for OCD, 5.5% for subclinical OCD and 4.7% for
      OC symptomatology. We did not find significant differences between genders or
      academic grade regarding OC symptoms and OCD, but more subclinical prevalence was
      found in males than in females. Socio-demographic variables were not related to
      any level of OCD, but academic performance was significantly lower in clinical
      OCD. The co-morbidity between OCD and any psychiatric disorder was high (85%) and
      higher for emotional disorders than for behavioral disorders. The impairment was
      associated with comorbidity and was worse for OCD with comorbid emotional
      problems. The results suggest that OCD is not rare in school children and
      adolescents and that it has an impact on their personal functioning. We suggest
      the possibility of an early diagnosis and treatment.

PMID- 22858902
TI  - Total synthesis of the proposed structure of cyclic hexadepsipeptide veraguamide
      A.
AB  - We have developed a practical method to assemble the proposed structure of
      natural product veraguamide A (1) by first preparing the three key fragments
      followed by optimization of the macrocyclization site. Although the synthetic
      product gave similar optical rotation to that reported for natural product,
      significant differences in the (1)H and (13)C NMR spectra were observed,
      especially the proton and carbon signals in the two N-MeVal moieties.

PMID- 22858903
TI  - Joining plasmonics with microfluidics: from convenience to inevitability.
AB  - Along the advances in optofluidics, functionalities based on the surface plasmon
      polariton have also been finding an increasing level of involvement within
      micro/nano-fluidic systems, gradually forming a new field of plasmo-fluidics.
      This survey of the burgeoning field reveals that judicious selection and
      combination of plasmonic and micro/nano-fluidic features render the plasmo
      fluidic integration useful and mutually beneficial to the point of inevitability.
      We establish categories for the level of integration and utilize them as a
      framework for surveying existing work and extracting future perspectives.

PMID- 22858904
TI  - Tubal ligation frequency in Oklahoma women with cervical cancer.
AB  - OBJECTIVE: Infrequent Pap screening is an important risk factor for cervical
      cancer. We studied the association between contraceptive methods, screening
      frequency, and cancer. METHODS: Women (n=2004) enrolled in the cross-sectional
      Study to Understand Cervical Cancer Endpoints and Determinants (SUCCEED)
      underwent colposcopy to evaluate an abnormal Pap test. Questionnaire data were
      compared between those with cervical intraepithelial neoplasia (CIN)
      3/adenocarcinoma in situ (AIS) and those with invasive cancer to identify factors
      associated with cancer. Logistic regression was used to calculate age-stratified
      measures of association between contraceptive method and Pap frequency as well as
      tubal ligation (TL) and cancer risk. RESULTS: In all age groups, women with TL
      were more likely to have had no Pap screening in the previous 5 years compared to
      women using other contraception: 26-35 years (OR 4.6, 95% CI 2.4-8.6; p<0.001),
      36-45 years (OR 3.8, 95% CI 2.1-7.0; p<0.001), and 46-55 years (OR 2.2, 95% CI
      1.0-4.9; p=0.050). Subjects with cancer (n=163) were more likely to have had a TL
      (41% vs. 21%, p<0.001) than those with CIN 3/AIS (n=370). Age-stratified analyses
      showed increased odds of tubal ligation in women with cancer versus those with
      CIN 3/AIS between 25 and 45 years, with a significant increase in women 26 to 35
      years old (OR 3.3, 95% CI 1.4-8.1; p=0.009). Adjusting for Pap frequency changed
      the effect only slightly, suggesting that increased risk was not fully mediated
      by lack of screening. CONCLUSION: Contraceptive type is associated with Pap
      screening. Women with TLs obtain less frequent Pap testing and may be at an
      increased risk for cervical cancer.

PMID- 22858905
TI  - Letter to the editor: corrections and comment to review of female sexual concerns
      in gynecologic cancer.

PMID- 22858907
TI  - Selection of antigen receptors in splenic marginal-zone lymphoma: further support
      from the analysis of the immunoglobulin light-chain gene repertoire.

PMID- 22858906
TI  - Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors.
AB  - FMS-like tyrosine kinase 3 (FLT3) normally functions in the
      survival/proliferation of hematopoietic stem/progenitor cells, but its
      constitutive activation by internal tandem duplication (ITD) mutations correlates
      with a poor prognosis in AML. The development of FLT3 tyrosine kinase inhibitors
      (TKI) is a promising strategy, but resistance that arises during the course of
      treatment caused by secondary mutations within the mutated gene itself poses a
      significant challenge. In an effort to predict FLT3 resistance mutations that
      might develop in patients, we used saturation mutagenesis of FLT3/ITD followed by
      selection of transfected cells in FLT3 TKI. We identified F621L, A627P, F691L and
      Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI.
      Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3
      autophosphorylation and signaling through MAP kinase, STAT5 and AKT in some
      mutants. Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed
      resistance to sorafenib in vivo but not to lestaurtinib. These results indicate a
      growing number of FLT3 mutations that are likely to be encountered in patients.
      Such knowledge, combined with known remaining sensitivity to other FLT3 TKI, will
      be important to establish as secondary drug treatments that can be substituted
      when these mutants are encountered.

PMID- 22858908
TI  - Lentiviral marking of patient-derived acute lymphoblastic leukaemic cells allows
      in vivo tracking of disease progression.

PMID- 22858909
TI  - Molecular mutations are prognostically relevant in AML with intermediate risk
      cytogenetics and aberrant karyotype.

PMID- 22858911
TI  - (35/37)Cl and (16/18)O isotope resolved 195Pt NMR: unique spectroscopic
      'fingerprints' for unambiguous speciation of [PtCl(n)(H2O)(6-n)](4-n) (n = 2-5)
      complexes in an acidic aqueous solution.
AB  - At high magnetic fields the 128.8 MHz (195)Pt NMR of all the species in the
      series [PtCl(n)(H(2)O)(6-n)](4-n) (n = 2-6) display unique (35/37)Cl isotope
      effects resulting in a unique 'fine-structure' of each individual resonance,
      which constitutes an unambiguous spectroscopic 'fingerprint' characteristic of
      the structure of the octahedral platinum(IV) complex, provided (195)Pt NMR are
      recorded at optimum magnetic field homogeneity and carefully controlled
      temperature (293 +/- 0.1 K). The detailed (195)Pt resonance fine-structure
      observed experimentally can readily be accounted for by an isotopologue and
      isotopomer model for each complex, showing particularly noticeable differences
      between stereoisomer pairs such as the cis/trans- and fac/mer-complexes. Moreover
      partial isotopic (18)O enrichment of the coordinated water molecules in the
      series [Pt(35/37)Cl(n)(H(2)(16/18)O)(6-n)](n-2) (n = 2-6) confirms this model.
      This technique can thus be considered a novel, direct spectroscopic method of
      chemical speciation of appropriate platinum(IV) complexes in solution without
      reference to accurate chemical shifts of authentic members of such a series.
      These effects are interpreted qualitatively in terms of the high sensitivity of
      (195)Pt NMR shielding to very small and subtle Pt-(35/37)Cl and Pt-(16/18)OH(2)
      bond displacements. Preliminary work shows this also applied to the corresponding
      bromido-complexes.

PMID- 22858910
TI  - Role of small intestinal bacterial overgrowth and Helicobacter pylori infection
      in chronic spontaneous urticaria: a prospective analysis.
AB  - The aim of this study is to assess the associations between chronic spontaneous
      urticaria (CSU), Helicobacter pylori infection and small intestinal bacterial
      overgrowth. Forty- eight patients with CSU were studied by scoring the urticaria
      activity and assesing the quality of life. Patients with H. pylori infection
      (n=11) or small intestinal bacterial overgrowth (n=13) were specifically treated
      for one week and clinically evaluated both before and 4 weeks after the
      eradication therapy. Eradication of H. pylori infection led to a significant
      improvement in CSU (p<0.002). In contrast, eradication of small intestinal
      bacterial overgrowth was not associated with any clinical improvement in CSU,
      despite the fact that these patients had statistically significant more urticaria
      activity at baseline. Thus there is no evidence to support the eradication of
      small intestinal bacterial overgrowth in CSU, but eradication of H. pylori
      infection may result in an improvement of the disease.

PMID- 22858912
TI  - Effect of ZnO nanofillers treated with triethoxy caprylylsilane on the isothermal
      and non-isothermal crystallization of poly(lactic acid).
AB  - The crystallization of PLA-silane surface-treated ZnO nanocomposites was
      investigated by DSC and compared to that of neat PLA. Several modes of
      crystallization were considered: isothermal and non-isothermal cold
      crystallization and also isothermal and non-isothermal melt crystallization. The
      kinetics of cold crystallization were studied using different methods, namely the
      Avrami and Ozawa-Flynn-Wall models, to calculate activation energies and kinetic
      constants. In contrast to what is typically observed when the foreign particles
      are added in a polymer matrix, the silane surface-treated ZnO delayed the
      crystallization of PLA and made it more difficult to start. The nucleation
      activity of the ZnO nanoparticles, phi, was calculated and found to be greater
      than 1 (phi = 1.7). This indicated that ZnO played an anti-nucleating role in the
      crystallization of PLA nanocomposites. This effect has been linked mainly to the
      interactions between the silane groups onto the surface of nanoparticles and PLA
      macromolecules. These interactions which reduce the mobility of polymer chains
      have been evidenced by rheological experiments.

PMID- 22858913
TI  - Role of cardiac imaging in heart failure.
AB  - Heart failure is the leading cause of mortality and rehospitalization in Western
      countries. With the development of new technologies applied to medical diagnostic
      pathways, cardiovascular imaging has rapidly gained ground. Therefore, the
      clinical cardiologist has to keep updated on the management of such innovative
      diagnostic tools which were once the exclusive domain of radiologists. The need
      to understand a new language is fundamental for the selection of diagnostic and
      therapeutic strategies in patients with heart failure, which is often the final
      destination for many cardiovascular diseases. Alongside standard diagnostic
      techniques such as chest radiography two-dimensional ultrasound and cardiac color
      Doppler, all of which are indispensable in daily practice, innovative tools have
      been defining their incremental role in cardiovascular imaging. Cardiac magnetic
      resonance (CMR), cardiac computed tomography (CT), speckle tracking, 3D
      echocardiography, new applications in nuclear medicine (SPECT MIBG), and "cardiac
      hybrid imaging" are emerging for research and are also playing a pivotal role in
      the clinical scenario. These techniques are useful the for non-invasive
      acquisition of diagnostic and prognostic information in heart failure. Whether
      the radiological and economic impact of these new technologies is sustainable is
      a question the clinical cardiologist will need to answer when considering the
      cost/benefit of the diagnostic tool selected among these methods.

PMID- 22858915
TI  - Current therapeutic strategies in cardiorenal syndrome.
AB  - Cardiorenal syndromes (CRS) are disorders of the heart and kidneys in which an
      acute or chronic dysfunction in one organ may induce acute or chronic dysfunction
      of the other. Primary disorders of one of these two organs often result in
      secondary dysfunction or injury of the other. The lack of specific trials in this
      field highlights the need for further studies aimed to assess titration and
      appropriate dosages of drugs, according to both the etiology of chronic heart
      failure (CHF) and also the severity of underlying renal dysfunction. Moreover,
      the most recent clinical trials evaluating clinical and renal outcome in acute
      heart failure syndromes (AHFS), failed to demonstrate an improvement in renal
      function and perfusion. Therefore, Current American and European Guidelines for
      AHFS does not provide specific recommendation for patients with renal impairment.
      In this scenario several questions regarding the drugs, their recommended dosage
      and potential adverse effects on cardiac and renal outcome need to be addressed.
      Subsequently, therapy inducing an improvement in the renal function, a reduction
      of neurohormonal activation and an improvement of renal blood flow, could lead to
      a reduction in mortality and hospitalization in patients with CRS.

PMID- 22858916
TI  - Contribution of natriuretic peptide testing and Doppler echocardiography at
      bedside to the diagnosis of acute heart failure. A practical overview.
AB  - Acute heart failure is one of the most common condition leading to hospital
      admission and is burdened by important mortality and readmission rates. A timely
      diagnosis of congestive heart failure at admission by hospitalists is essential
      for an early and tailored medical management. The initial clinical evaluation
      based on symptoms, physical signs and chest radiography remains inconclusive for
      the diagnosis in many patients with acute dyspnea, and the use of natriuretic
      peptide testing (BNP and NT-proBNP) through a two cut-point strategy is currently
      recommended as first-line diagnostic complement in the acute care setting.
      Bedside Doppler echocardiography is another reliable, noninvasive method that
      offers additional diagnostic information over the initial clinical evaluation.
      Along with echocardiographic evidence of depressed left ventricular systolic
      function, several simple Doppler indexes have been validated in the emergency
      diagnosis of congestive heart failure. Doppler echocardiography at bedside may
      especially benefit to patients with intermediate, inconclusive natriuretic
      peptide concentrations. The aim of the present review was to offer to the
      hospitalist a practical overview on the relative contribution of natriuretic
      peptide testing and bedside Doppler echocardiography to the diagnosis of acute
      heart failure in the emergency care setting.

PMID- 22858914
TI  - Gene and cell therapies for the failing heart to prevent sudden arrhythmic death.
AB  - Current therapies for treatment and prevention of sudden cardiac death have
      certain limitations, and a search for new therapeutic approaches is desirable to
      reduce the burden of sudden arrhythmic death. Gene therapy and stem cell therapy
      have been investigated as new, valuable tools in treating cardiac diseases such
      as arrhythmias. In this review, the basics of each modality, important related
      experimental and clinical studies, and potential advantages and limitations of
      these treatments will be discussed. The future success of gene and cell therapy
      to become practical clinical tools greatly depends on our understanding of the
      mechanisms of ventricular arrhythmia and the mechanisms of action of gene and
      cell therapy.

PMID- 22858917
TI  - Ventricular assist devices in acute heart failure.
AB  - In Western countries, the incidence of acute heart failure has been growing
      rapidly and is associated with increased incidence of mortality. Acute heart
      failure encompasses an extended spectrum of clinical presentation. From these,
      cardiogenic shock remains its most dramatic entity and is burdened by a dismal
      prognosis. As the initial therapeutic armamentarium (pressor agents, non-invasive
      or invasive ventilation using positive end-expiratory pressure, treatment of the
      damaging agent, ultrafiltration and intra-aortic balloon counterpulsation) might
      be soon overcome, implantation of mechanical ventricular assistance should be
      considered. Constant technical improvements have allowed quick and percutaneous
      implantation of such left ventricular assistance devices (LVADs). Herein, we
      review the technical characteristics and clinical data of the percutaneous LVADs
      currently available in Europe for treatment of overt cardiogenic shock.

PMID- 22858918
TI  - [Severe intermittent claudication: PGE1 treatment. A 40-week registry, efficacy
      and costs].
AB  - AIM: Intermittent claudication (IC) in peripheral vascular disease is
      characterized by lower limb pain appearing on effort. Treatment with PGE1 has
      been successfully used to manage IC patients. This registry has evaluated safety
      and costs of PGE1 in the management of IC. METHODS: In this study a long-term
      treatment protocol (LTP), a short-term protocol (STP) and an outpatient (OP), "on
      demand" treatment have been compared. A treadmill effort test has been used to
      evaluate walking distance. The follow up for these three protocols was 40 weeks.
      PGE1 treatment was associated to a risk reduction plan and to an exercise
      program. RESULTS: The final analysis has included 252 LTP patients, 223 STP
      patients and 284 OP patients (total 659 valid cases). A group of 171 comparable
      patients not treated with PGE1 was used for a parallel comparison. Cardiovascular
      mortality and morbidity has been evaluated in 731 PGE1 patients completing 24
      months of follow up. All protocols have been well tolerated. No side effects were
      observed. The lower cost has been observed for OP patients. In the long term,
      mortality and morbidity were lower in patients treated with PGE1 in comparison
      with patients not treated with PGE1. CONCLUSION: Considering costs and results
      (increase in walking distance) and improvement in Karnofsky scale the STP plan
      appears to be better than LTP for IC patients. The OP, "on-demand" treatment
      offers further improvements. This last treatment plan is simpler; the plan allows
      better timing for exercise. The treatment can be used even in non-specialized
      centers.

PMID- 22858919
TI  - Intracoronary local paclitaxel delivery by X-ray contrast media for in-stent
      restenosis: a clinical pilot study to assess safety and tolerability.
AB  - AIM: Non-stent-based immediate release formulations of paclitaxel have been shown
      to reduce in-stent restenosis in animal experiments and clinical trials. In the
      porcine overstretch model paclitaxel dissolved in the contrast medium iopromide
      inhibited neointimal proliferation in a dose-dependent manner after intracoronary
      injection and was well tolerated. METHODS: As a first step entering clinical
      development, a phase I trial was performed using four ascending paclitaxel
      dose/concentration levels: samples of up to 100 mL of the contrast medium
      (iopromide) containing 10, 50, 100 or 200 uM paclitaxel or iopromide (controls)
      were randomly administered to patients assigned to bare metal stent implantation
      for single de novo coronary artery lesions. Safety variables, tolerability and
      angiographic parameters were assessed. RESULTS: Adverse events, ECG, systolic and
      diastolic blood pressure, left ventricular ejection fraction, leukocyte count,
      other hematological or clinical chemistry data did not reveal any trend which
      could be related to the study medication. Short-lasting serum paclitaxel
      concentrations remained significantly below those known from cancer therapy.
      Angiographic late lumen loss was 0.72+/-0.50 mm (N.=7) in controls versus 0.45+/
      0.65 mm (N.=17) in all paclitaxel-treated patients; binary restenosis rate was
      5/7(63%) versus 6/17 (35%) and target lesion revascularization rate was 4/8 (50%)
      versus 4/24 (17%). CONCLUSION: Intracoronary infusion of paclitaxel dissolved in
      an X-ray contrast medium was well tolerated. The results show restenosis
      inhibition, but the number of patients examined was too small to demonstrate a
      statistically significant inhibition.

PMID- 22858920
TI  - Emerging oral anticoagulants for stroke prevention in patients with non-valvular
      atrial fibrillation.
AB  - In patients with atrial fibrillation (AF) warfarin has been the mainstay therapy
      for stroke prevention. In recent randomized clinical trials (RCTs) oral direct
      thrombin inhibitor (Dabigatran) and factor Xa inhibitors (Rivaroxaban and
      Apixaban) challenged the efficacy and safety benchmarks set by warfarin. These
      drugs boast a rapid onset of action, shorter half-life and fewer drug and dietary
      interactions. Moreover, these new anticoagulants do not require monitoring,
      titration or dose adjustments. These agents have already been approved for
      prevention of stroke or systemic embolism in patients with AF. Uncertainty
      regarding suitability, efficacy and safety in certain patient subsets and issues
      related to the ability effectively monitor the pharmacodynamic effects and
      reverse the therapeutic effects of these drugs should be addressed as we engage
      in a widespread use of these agents in various patient subsets.

PMID- 22858921
TI  - Hepatic artery aneurysm treatment with heparin-bonded covered stent: a case
      report.
AB  - The hepatic artery is the second most common site for aneurysms formation within
      the splanchnic circulation. Most hepatic artery aneurysms (HAA) are diagnosed
      incidentally by a computed tomography(CT) scan or a Doppler ultrasonography. We
      present the case of a HAA diagnosed preoperatively in a 82-year old man, who was
      treated with an endovascular procedure. An abdominal ultrasonography revealed by
      chance the presence of a HAA. The abdominal CT scan confirmed an aneurysm of the
      common hepatic artery, specifically at the origin of the gastroduodenal artery.
      The gastroduodenal artery was embolized using coils then a heparin-bonded covered
      stent was deployed into the common hepatic artery to exclude the aneurysm. Final
      arteriogram documented the regular patency of the stent and the complete
      exclusion of the aneurysm. No complication occurred and the patient was
      discharged on the second postoperative day. Six months later, a follow-up with a
      Duplex scan confirmed the regular patency of the stent, and the patient was in
      good clinical conditions.

PMID- 22858922
TI  - Usefulness of computed tomography to detect restenosis after coronary stent
      implantation.

PMID- 22858923
TI  - When coronary angiography is not enough to detect spontaneous left main coronary
      artery dissection.

PMID- 22858924
TI  - Treatment of superficial and profunda femoral artery bifurcation lesions: still a
      procedure only for surgeons?

PMID- 22858925
TI  - Simultaneous thromboses of two coronary arteries in a heavy smoker woman: a
      singular case of acute myocardial infarction.

PMID- 22858926
TI  - Multifaceted allergen avoidance during infancy reduces asthma during childhood
      with the effect persisting until age 18 years.
AB  - BACKGROUND: Asthma is a chronic disease that often starts in childhood. The key
      risk factors are a child's environment and their genetic characteristics. The aim
      of this study was to evaluate the efficacy of environmental modification in the
      first 12 months of life on the prevalence of asthma in high-risk individuals.
      METHODS: Children (n=120) considered at high risk of allergic disorders (either
      dual heredity or single heredity and a high cord total IgE), were enrolled in a
      single-blinded, randomised controlled trial. Infants in the intervention arm were
      either breast fed with the mother on a low allergen diet or given an extensively
      hydrolysed formula. Exposure to house dust mite allergen was reduced. The control
      group followed standard advice. Children were assessed at ages 1, 2, 4, 8 and 18
      years for the presence of asthma and atopy. RESULTS: At 18 years of age, there
      was a significantly lower prevalence of asthma in the prevention group compared
      with the control group (OR: 0.23, 95% CI 0.08 to 0.70, p=0.01), primarily due to
      asthma that developed during childhood but persisted until age 18 years. Repeated
      measure analysis showed that there was an overall reduction in asthma prevalence
      from 1 to 18 years (OR: 0.51, CI 0.32 to 0.81, p=0.04). Prevalence of atopy was
      not significantly different between the two groups at age 18. CONCLUSION:
      Comprehensive allergen avoidance in the first year of life is effective in
      preventing asthma onset in individuals considered at high risk due to heredity.
      The effect occurs in the early years, but persists through to adulthood.

PMID- 22858927
TI  - Natural history of successive COPD exacerbations.

PMID- 22858928
TI  - The FDA-mandated trial of safety of long-acting beta-agonists in asthma: finality
      or futility?

PMID- 22858929
TI  - The influence of matriptase-2 on prostate cancer in vitro: a possible role for
      beta-catenin.
AB  - The type II transmembrane serine proteases (TTSPs) are a family of cell surface
      proteolytic enzymes contributing to a number of processes, such as tumour
      invasion and metastasis. Within the TTSPs, matriptase-2 is a relatively newly
      identified member and this protease has been shown to play a key role in cancer
      progression. beta-catenin has long been regarded as an oncogene. The deregulation
      of the beta-catenin signalling pathway plays a significant role in the
      progression and possibly the development of cancer. However, little is known
      about the role of matriptase-2 in prostate cancer. This study aimed to examine
      the correlation between matriptase-2 and beta-catenin. Matriptase-2 was knocked
      down in the normal prostate cells, PZHPV7 and PNT2C2, using a ribozyme transgene
      targeting matriptase-2. The altered cells were used in a number of in vitro
      experiments designed to investigate the involvement of matriptase-2 with beta
      catenin and to further characterise its function. The knockdown of matriptase-2
      had no effect on cell growth or adhesion but significantly reduced cell motility
      (PZHPV7 cells, p<0.001; PNT2C2 cells, p=0.001 vs. respective control cells) and
      invasive capability (PZHPV7 cells, p=0.001; PNT2C2 cells, p=0.007). The knockdown
      also caused a large increase in beta-catenin protein expression at the cell
      membrane in PZHPV7 and PNT2C2 cells and a decrease in PC3 cells overexpressing
      matriptase-2, but did not affect the mRNA levels. Matriptase-2 may have an
      important impact on prostate cancer progression. The data gained from this study
      suggest that matriptase-2 protects against the development and progression of
      prostate cancer by regulating the motility and invasive capabilities of prostate
      cancer cells. Matriptase-2 also reduces the levels of beta-catenin at the cell
      membrane. As beta-catenin is highly involved in the regulation of cellular
      processes, including motility and invasion, the reduction of beta-catenin
      expression by matriptase-2 may be a possible mechanism by which matriptase-2
      functions.

PMID- 22858930
TI  - OCT skin image enhancement through attenuation compensation.
AB  - The enhancement of optical coherence tomography (OCT) skin images can help
      dermatologists investigate the morphologic information of the images more
      effectively. In this paper, we propose an enhancement algorithm with the stages
      that includes speckle reduction, skin layer detection, and attenuation
      compensation. A weighted median filter is designed to reduce the level of speckle
      while preserving the contrast. A novel skin layer detection technique is then
      applied to outline the main skin layers: stratum corneum, epidermis, and dermis.
      The skin layer detection algorithm does not make any assumption about the
      structure of the skin. A model of the light attenuation is then used to estimate
      the attenuation coefficient of the stratum corneum, epidermis, and dermis layers.
      The performance of the algorithm has been evaluated qualitatively based on visual
      evaluation and quantitatively using two no-reference quality metrics: signal-to
      noise ratio and contrast-to-noise ratio. The enhancement algorithm is tested on
      35 different skin OCT images, which show significant improvements in the quality
      of the images, especially in the structures at deeper levels.

PMID- 22858931
TI  - Fabrication of concave and convex potassium bromide lens arrays by compression
      molding.
AB  - A new simple and cost-effective method has been developed for the fabrication of
      both plano-convex and plano-concave lens arrays with potentially important sag
      heights. The process is based on the use of potassium bromide (KBr) powder. At
      ambient temperature and under pressure, KBr powder is compressed on a molding die
      with the desired shape to form a solid lens array. The quality of the lens arrays
      has been assessed, and we present the first image produced by a converging KBr
      lens array.

PMID- 22858932
TI  - Flexible error-reduction method for shape measurement by temporal phase
      unwrapping: phase averaging method.
AB  - Temporal phase unwrapping is an important method for shape measurement in
      structured light projection. Its measurement errors mainly come from both the
      camera noise and nonlinearity. Analysis found that least-squares fitting cannot
      completely eliminate nonlinear errors, though it can significantly reduce the
      random errors. To further reduce the measurement errors of current temporal phase
      unwrapping algorithms, in this paper, we proposed a phase averaging method (PAM)
      in which an additional fringe sequence at the highest fringe density is employed
      in the process of data processing and the phase offset of each set of the four
      frames is carefully chosen according to the period of the phase nonlinear errors,
      based on fast classical temporal phase unwrapping algorithms. This method can
      decrease both the random errors and the systematic errors with statistical
      averaging. In addition, the length of the additional fringe sequence can be
      changed flexibly according to the precision of the measurement. Theoretical
      analysis and simulation experiment results showed the validity of the proposed
      method.

PMID- 22858933
TI  - Preflight calibration of the Imaging Magnetograph eXperiment polarization
      modulation package based on liquid-crystal variable retarders.
AB  - We present the study, characterization, and calibration of the polarization
      modulation package (PMP) of the Imaging Magnetograph eXperiment (IMaX)
      instrument, a successful Stokes spectropolarimeter on board the SUNRISE balloon
      project within the NASA Long Duration Balloon program. IMaX was designed to
      measure the Stokes parameters of incoming light with a signal-to-noise ratio of
      at least 10<sup>3</sup>, using as polarization modulators two nematic liquid
      crystal variable retarders (LCVRs). An ad hoc calibration system that reproduced
      the optical and environmental characteristics of IMaX was designed, assembled,
      and aligned. The system recreates the optical beam that IMaX receives from
      SUNRISE with known polarization across the image plane, as well as an optical
      system with the same characteristics of IMaX. The system was used to calibrate
      the IMaX PMP in vacuum and at different temperatures, with a thermal control
      resembling the in-flight one. The efficiencies obtained were very high, near
      theoretical maximum values: the total efficiency in vacuum calibration at nominal
      temperature was 0.972 (1 being the theoretical maximum). The condition number of
      the demodulation matrix of the same calibration was 0.522 (0.577 theoretical
      maximum). Some inhomogeneities of the LCVRs were clear during the pixel-by-pixel
      calibration of the PMP, but it can be concluded that the mere information of a
      pixel-per-pixel calibration is sufficient to maintain high efficiencies in spite
      of inhomogeneities of the LCVRs.

PMID- 22858934
TI  - Single-shot two-dimensional surface measurement based on spectrally resolved
      white-light interferometry.
AB  - By analyzing the spectral domain's phase information, one can use spectrally
      resolved white-light interferometry (SRWLI) to obtain the profile with a single
      frame of an interferogram. We present here a two-dimensional (2D) SRWLI method
      that can be applied to measure narrow rectangle areas. A frequency comb is
      produced by using a Fabry-Perot (F-P) etalon to filter the broadband source. With
      the filtered frequency comb illumination, the interference patterns under
      adjacent wavelengths would be separated by a little distance, which enables us to
      obtain a 2D profile with a small width. The experimental details of measurement
      on a step sample are discussed in this paper.

PMID- 22858935
TI  - Optical correlator based target detection, recognition, classification, and
      tracking.
AB  - A dedicated automatic target recognition and tracking optical correlator (OC)
      system using advanced processing technology has been developed. Rapidly cycling
      data-cubes with size, shape, and orientation are employed with software
      algorithms to isolate correlation peaks and enable tracking of targets in
      maritime environments with future track prediction. The method has been found
      superior to employing maximum average correlation height filters for which the
      correlation peak intensity drops off in proportion to the number of training
      images. The physical dimensions of the OC system may be reduced to as small as 2
      in. * 2 in. * 3 in. (51 mm * 51 mm * 76 mm) by modifying and minimizing the OC
      components.

PMID- 22858936
TI  - Phase unwrapping for noisy phase map using localized compensator.
AB  - Phase unwrapping for a noisy image suffers from many singular points. Singularity
      spreading methods are useful for the noisy image to regularize the singularity.
      However, the methods have a drawback of distorting phase distribution in a
      regular area that contains no singular points. When the singular points are
      confined in some local areas, the regular region is not distorted. This paper
      proposes a new phase unwrapping algorithm that uses a localized compensator
      obtained by clustering and by solving Poisson's equation for the localized areas.
      The numerical results demonstrate that the proposed method can improve the
      accuracy compared with other singularity-spreading methods.

PMID- 22858937
TI  - Closely packed hexagonal conical microlens array fabricated by direct laser
      photopolymerization.
AB  - We apply femtosecond laser direct writing in photopolymers for manufacturing of
      conical microlenses and closely packed arrays thereof. We demonstrate the
      fabrication of high optical quality axicons of 15 um in radius, having 150
      degrees , 160 degrees , and 170 degrees  cone angles. Their optical properties
      and performance are modeled using the finite-difference time-domain method and
      compared with experimentally measured data. Additionally, optimization of the
      laser direct writing parameters regarding these types of micro-objects is
      presented. Possible applications of closely packed arrays of axicon microlenses
      are discussed, having potential attractivity in the fields of modern microscopy,
      light-based material processing, particle manipulation in microfluidic, and
      optofluidic applications.

PMID- 22858938
TI  - Design of interference using coherent beams configured as a six-sided pyramid.
AB  - Various interference pattern formations have been investigated using six
      countering laser beams that form a six-sided pyramid. Phase shift and amplitude
      variations among the interfering beams are very useful for designing interference
      patterns summarized here. The interference patterns are categorized into 32 unit
      figures, and structural changes with different thresholds are investigated in
      detail.

PMID- 22858939
TI  - Performance comparison of an all-fiber-based laser Doppler vibrometer for remote
      acoustical signal detection using short and long coherence length lasers.
AB  - All-fiber laser Doppler vibrometer systems have great potential in the
      application of remote acoustic detection. However, due to the requirement for a
      long operating distance, a long coherence length laser is required, which can
      drive the system cost high. In this paper, a system using a short coherence
      length laser is proposed and demonstrated. Experimental analysis indicates that
      the multi-longitudinal modes of the laser cause detection noise and that the
      unequal length between two paths (local oscillator path and transmission path)
      increases the intensity and the frequency components of the noise. In order to
      reduce the noise, the optical length of the two paths needs to be balanced,
      within the coherence length of the source. We demonstrate that adopting a tunable
      optical delay to compensate the unequal length significantly reduces the noise.
      In a comparison of the detection results by using a short coherence laser and a
      long coherence laser, our developed system gives a good performance on the
      acoustic signal detection from three meters away.

PMID- 22858940
TI  - Nanoscale all-optical plasmonic switching using electromagnetically induced
      transparency.
AB  - An all-optical switch composed of two interacting nanoparticles in front of an
      optical dielectric slab waveguide is proposed. An incident optical signal is
      coupled to the optical waveguide after scattering by the two nanoparticles. The
      scattered fields interfere constructively or destructively depending on the
      degree of optical transparency the nanoparticles induced by an optical control
      signal. The considered nanoparticles have a metallic core coated by an outer
      shell with three-level clusters such that the nanoparticles can exhibit
      electromagnetically induced transparency. A dipole-approximation model-based
      analysis reveals that a high rejection ratio can be achieved using the proposed
      configuration.

PMID- 22858941
TI  - Modal wavefront reconstruction based on Zernike polynomials for lateral shearing
      interferometry: comparisons of existing algorithms.
AB  - Four modal methods of reconstructing a wavefront from its difference fronts based
      on Zernike polynomials in lateral shearing interferometry are currently
      available, namely the Rimmer-Wyant method, elliptical orthogonal transformation,
      numerical orthogonal transformation, and difference Zernike polynomial fitting.
      The present study compared these four methods by theoretical analysis and
      numerical experiments. The results show that the difference Zernike polynomial
      fitting method is superior to the three other methods due to its high accuracy,
      easy implementation, easy extension to any high order, and applicability to the
      reconstruction of a wavefront on an aperture of arbitrary shape. Thus, this
      method is recommended for use in lateral shearing interferometry for wavefront
      reconstruction.

PMID- 22858942
TI  - Discrimination of serum Raman spectroscopy between normal and colorectal cancer
      using selected parameters and regression-discriminant analysis.
AB  - Raman spectroscopy of tissues has been widely studied for the diagnosis of
      various cancers, but biofluids were seldom chosen as the analyte because of the
      low concentration. Herein, serum of 30 normal people, 46 colon cancer, and 44
      rectum cancer patients were measured using Raman spectra and analyzed. The
      information of Raman peaks (intensity and width) and that of the fluorescence
      background (baseline function coefficients) were selected as parameters for
      statistical analysis. Principal component regression (PCR) and partial least
      square regression (PLSR) were used on the selected parameters separately to see
      the diagnosing performance of the parameters. PCR performed better than PLSR in
      our spectral data. Then linear discriminant analysis (LDA) was used on the
      principal components (PCs) of the two regression methods on the selected
      parameters, and the diagnostic accuracy were 88% and 83%. The conclusion is that
      the selected parameters can maintain the information of the original spectra well
      and Raman spectroscopy of serum has the potential for the diagnosis of colorectal
      cancer.

PMID- 22858943
TI  - Tomographic imaging of ratiometric fluorescence resonance energy transfer in
      scattering media.
AB  - A method to visualize and quantify fluorescence resonance energy transfer (FRET)
      in scattering media is proposed. It combines the ratiometric FRET method with
      fluorescence molecular tomography (FMT) in continuous wave (CW) mode. To evaluate
      the performance of the proposed method, experiments on a tissue-mimicking phantom
      are carried out. The results demonstrate that the proposed approach is capable of
      visualizing and quantifying the FRET distribution in scattering media, which
      implies the further application of the ratiometric assay in in vivo studies.

PMID- 22858944
TI  - Improved infrared target-tracking algorithm based on mean shift.
AB  - An improved IR target-tracking algorithm based on mean shift is proposed herein,
      which combines the mean-shift-based gradient-matched searching strategy with a
      feature-classification-based tracking algorithm. An improved target
      representation model is constructed by considering the likelihood ratio of the
      gray-level features of the target and local background as a weighted value of the
      original kernel histogram of the target region. An expression for the mean-shift
      vector in this model is derived, and a criterion for updating the model is
      presented. Experimental results show that the algorithm improves the shift weight
      of the target pixel gray level and suppresses background disturbance.

PMID- 22858945
TI  - White-light ellipsometer with geometric phase shifter.
AB  - We describe a simple spectroscopic ellipsometer that uses a geometric phase
      shifter and a white-light source to generate a small number of phase-stepped
      intensities I(lambda), which are recorded by a spectrometer. The ellipsometric
      angles psi and Delta are easily calculated from these intensities at each
      wavelength simultaneously. We show that errors in Delta due to the nonideal
      behavior of the achromatic quarter-wave plate in the phase shifter can be made
      small by suitably adjusting the azimuth of the linearly polarized light incident
      on the sample. Two silicon dioxide films were measured with this instrument
      between 450 and 850 nm and yielded best fit film thicknesses of 1000.6+/-0.1 A
      and 20.6+/-0.1 A, in excellent agreement with those obtained using a commercial
      ellipsometer.

PMID- 22858946
TI  - Nanometer displacement measurement using Fresnel diffraction.
AB  - We introduce a relatively simple and efficient optical technique to measure
      nanoscale displacement based on visibility variations of the Fresnel diffraction
      fringes from a two-dimensional phase step. In this paper we use our technique to
      measure electromechanical expansions by a thin piezoelectric ceramic and also
      thermal changes in the diameter of a tungsten wire. Early results provide
      convincing evidence that sensitivity up to a few nanometers can be achieved, and
      our technique has the potential to be used as a nanodisplacement probe.

PMID- 22858947
TI  - Effect of paramagnetic magnetization in Faraday isolators.
AB  - The influence of paramagnetic magnetization of magneto-optical elements on the
      characteristics of Faraday isolators is studied. The theoretical estimates
      confirmed by the experiment indicate that this effect should be taken into
      consideration, particularly when designing large-aperture and cryogenic Faraday
      isolators.

PMID- 22858948
TI  - Two-beam nonlinear Kerr effect to stabilize laser frequency with sub-Doppler
      resolution.
AB  - Avoiding laser frequency drifts is a key issue in many atomic physics
      experiments. Several techniques have been developed to lock the laser frequency
      using sub-Doppler dispersive atomic lineshapes as error signals in a feedback
      loop. We propose here a two-beam technique that uses nonlinear properties of an
      atomic vapor around sharp resonances to produce sub-Doppler dispersivelike
      lineshapes that can be used as error signals. Our simple and robust technique has
      the advantage of not needing either modulation or magnetic fields.

PMID- 22858949
TI  - Comparison of optically derived particle size distributions: scattering over the
      full angular range versus diffraction at near forward angles.
AB  - The volume scattering function (VSF) of particles in water depends on the
      particles' size distribution and composition as well as their shape and internal
      structure. Inversion of the VSF thus provides information about the particle
      population. The commercially available LISST instrument measures the scattering
      at near forward angles to estimate the bulk size distribution of particles larger
      than about 1 MUm. By using scattering over the full angular range (0 degrees -180
      degrees ), the recently improved VSF-inversion method [X. Zhang, M. Twardowski,
      and M. Lewis, Appl. Opt. 50, 1240 (2011).] can characterize particles in terms of
      particle subpopulations, which are described by their unique size distribution
      and composition. Concurrent deployments of the Multispectral Volume Scattering
      Meter and the LISST in three coastal waters (i.e., Chesapeake Bay, Mobile Bay,
      and Monterey Bay) allowed us to compare the size distributions derived from these
      two different methods. We also obtained indirect validation of the results for
      submicrometer particles and for the composition of particles provided by the VSF
      inversion method. For particle sizes ranging from 1 to 100 MUm, the concentration
      was shown to vary over 10 orders of magnitude, and excellent agreement was found
      between the two methods with a mean relative difference less than 10% for the
      total size distributions. The inversion results also reproduced spectral
      variations in the shape of the VSF, although these spectral variations were not
      frequently observed in our study. The increased backscattering towards the
      shorter wavelengths was explained by the stronger influence of submicrometer
      particles affecting the backscattering. Based on published measurements of cell
      sizes and intracellular chlorophyll-a [Chl] concentrations over a wide range of
      phytoplankton species and strains, [Chl] was estimated for the inverted
      subpopulations that were identified as phytoplankton based on their refractive
      index and mean sizes. The estimated [Chl] agreed well with the fluorescence-based
      estimates in both magnitude and trend, thus reproducing a bloom event observed at
      a time series station.

PMID- 22858950
TI  - Dual-modulator broadband infrared Mueller matrix ellipsometry.
AB  - A broadband mid-infrared Mueller matrix ellipsometer is described based on two
      photoelastic modulators and a step-scan interferometer. The data are analyzed
      using a combination hardware-software double Fourier transformation. Obtaining
      spectra of the Mueller matrix elements requires that the infrared wavelength
      dependent retardation amplitude of the modulators be known through calibration
      and subsequently incorporated into the data processing. The spectroscopic
      capability of the instrument is demonstrated in transmission and reflection
      geometries by the measured Mueller matrices of air, an anisotropic quartz
      crystal, and the ZnSe-water interface, each from 2500-4000 cm(-1).

PMID- 22858951
TI  - Photodetector performance enhancement using an electron accelerator controlled by
      light.
AB  - A new method of photodetector performance enhancement using an embedded optical
      accelerator circuit within the photodetector is proposed. The principle of
      optical tweezer generation using a light pulse within a PANDA ring is also
      reviewed. By using a modified add-drop optical filter known as a PANDA microring
      resonator, which is embedded within the photodetector circuit, the device
      performance can be improved by using an electron injection technique, in which
      electrons can be trapped by optical tweezers generated by a PANDA ring resonator.
      Finally, electrons can move faster within the device via the optical waveguide
      without trapping center in the silicon bulk to the contact, in which the increase
      in photodetector current is seen. Simulation results obtained have shown that the
      device's light currents are increased by the order of four, and the switching
      time is increased by the order of five. This technique can be used for better
      photodetector performance and other semiconductor applications in the future.

PMID- 22858952
TI  - Single-crystal magneto-optic sensor with electrically adjustable sensitivity.
AB  - A novel magneto-optic sensor with electrically adjustable sensitivity is proposed
      that is based on the approximate multiplication correlation between the linear
      electro-optic phase retardation and the Faraday magneto-optic rotation angle in a
      single bismuth germanate crystal. The measurement sensitivity and its temperature
      stability, linear and monotonic measurement ranges of the proposed sensor can be
      controlled in real time by adjusting the modulating voltage applied to the
      sensing crystal. In particular, the proposed sensor can be used for the precise
      measurement of dc magnetic field or dc current. The basic sensing performance is
      theoretically analyzed and experimentally demonstrated by dc current measurement.

PMID- 22858953
TI  - Compact Q-switched and mode-locked Nd3+:YVO4/Cr4+:YAG self-Raman laser.
AB  - Compact passively Q-switched and mode-locked Nd(3+):YVO(4)/Cr(4+):YAG self-Raman
      laser with high mode-locked repetition rate was demonstrated. The picosecond
      first Stokes at 1176 nm was successfully obtained. At the maximum incident pump
      power, the average output power was 95 mW with the mode-locked pulse repetition
      rate of 940 MHz. Yellow laser output of 588.2 nm was also realized by the use of
      LiB(3)O(5) frequency doubling crystal.

PMID- 22858954
TI  - Estimation of a lidar's overlap function and its calibration by nonlinear
      regression.
AB  - The overlap function of a Raman channel for a lidar system is retrieved by
      nonlinear regression using an analytic description of the optical system and a
      simple model for the extinction profile, constrained by aerosol optical
      thickness. Considering simulated data, the scheme is successful even where the
      aerosol profile deviates significantly from the simple model assumed. Application
      to real data is found to reduce by a factor of 1.4-2.0 the root-mean-square
      difference between the attenuated backscatter coefficient as measured by the
      calibrated instrument and a commercial instrument.

PMID- 22858955
TI  - Optimization of all-garnet magneto-optical magnetic field sensors with genetic
      algorithm.
AB  - In this article, we introduce a simple magnetophotonic crystal structure for
      magnetic field sensing applications. Design procedure, which is performed using a
      global optimization tool called genetic algorithm, provides great flexibility for
      structures with layers having nonquarter-wavelength thickness. Results show that
      our proposed genetic sensor comparatively exhibits higher simplicity,
      sensitivity, and spatial resolution, with better photo-response and performance.
      We also analyze the underlying physical phenomenon responsible for such
      improvement by inspection of electric field distribution in the interior of the
      structure.

PMID- 22858956
TI  - Design of diffractive phase element for modulating the electric field at the out
      of-focus plane in a lens system.
AB  - We demonstrate an efficient method to design the diffractive phase element for
      modulating the electric field at the out-of-focus plane of a lens system by using
      an equivalent Fresnel diffraction in free space. In the monochromatic
      illumination, we show an example to certify the validity of our method
      experimentally. In the nonmonochromatic illumination, we theoretically display
      that the spectral beam splitting and highly confined intensity can be obtained
      simultaneously at the out-of-focus plane, which has the potential in the solar
      concentrating system and optical encryption.

PMID- 22858957
TI  - Algorithm for automated analysis of surface vibrations using time-averaged
      digital speckle pattern interferometry.
AB  - A fully automated algorithm was developed for the recording and analysis of
      vibrating objects with the help of digital speckle pattern interferometry
      utilizing continuous-wave laser light. A series of measurements were performed
      with increasing force inducing vibration to allow the spatial distribution of
      vibration amplitude to be reconstructed on the object's surface. The developed
      algorithm uses Hilbert transformation for an independent, quantitative evaluation
      of the Bessel function at every point of the investigated surface. The procedure
      does not require phase modulation, and thus can be implemented within any, even
      the simplest, DSPI apparatus. The proposed deformation analysis is fast and
      computationally inexpensive.

PMID- 22858958
TI  - Determination of quality and adulteration of tequila through the use of surface
      plasmon resonance.
AB  - In this work, the surface plasmon resonance (SPR) technique is used to determine
      the quality or adulteration of tequila beverages. Graphic analyses of the
      position and width of the SPR curve are related to the complex refractive index
      of the sample, showing differentiated regions where one can easily and
      unambiguously identify white, aged, or extra-aged tequilas, and even adulterated
      or low quality tequilas. The curves generated by aged and extra-aged tequilas,
      with respect to those obtained from white tequilas, are wider, while the resonant
      peak shifts towards larger angles. This behavior should be attributed to the
      aging process. The resonance curve is generated in 20 s, minimizing the
      variations of the SPR curve parameters due to temperature fluctuations.

PMID- 22858959
TI  - Optical reconfiguration by anisotropic diffraction in holographic polymer
      dispersed liquid crystal memory.
AB  - Holographic polymer dispersed liquid crystal (HPDLC) memory is fabricated by a
      photoinduced phase separation comprised of polymer and liquid crystal (LC) phases
      using laser light interference exposures. The anisotropic diffraction induced by
      the alignment of LC in the periodic structure of the HPDLC memory is applied to
      reconstruct the configuration contexts for the optically reconfigurable gate
      arrays. Optical reconfiguration for various circuits under parallel
      programmability is implemented by switching the polarization state of incident
      light on the HPDLC memory using a spatial light modulator.

PMID- 22858960
TI  - Full investigation of the resonant frequency servo loop for resonator fiber-optic
      gyro.
AB  - Resonator fiber-optic gyro (RFOG) is a high-accuracy inertial rotation sensor
      based on the Sagnac effect. A high-accuracy resonant frequency servo loop is
      indispensable for a high-performance RFOG. It is composed of a frequency
      discriminator, a loop filter, and a laser actuator. Influences of the loop
      parameters are fully developed. Optimized loop parameters are obtained by
      considering the noise reduction and wide dynamic performance of the RFOG. As a
      result, with the integration time of 10 s, the accuracy of the resonant frequency
      loop is increased to 0.02 Hz (1sigma). It is equivalent to a rotation rate of
      0.067 degrees /h, which is close to the shot noise limit for the RFOG, while a
      minimum rotation of +/-0.05 degrees /s has been carried out simultaneously. These
      are the best results reported to date, to the best of our knowledge, for an RFOG
      using the miniature semiconductor laser that benefits from the optimization of
      the resonant frequency servo-loop parameters.

PMID- 22858961
TI  - Instrumental error in chromotomosynthetic hyperspectral imaging.
AB  - Chromotomosynthetic imaging (CTI) is a method of convolving spatial and spectral
      information that can be reconstructed into a hyperspectral image cube using the
      same transforms employed in medical tomosynthesis. A direct vision prism
      instrument operating in the visible (400-725 nm) with 0.6 mrad instantaneous
      field of view (IFOV) and 0.6-10 nm spectral resolution has been constructed and
      characterized. Reconstruction of hyperspectral data cubes requires an estimation
      of the instrument component properties that define the forward transform. We
      analyze the systematic instrumental error in collected projection data resulting
      from prism spectral dispersion, prism alignment, detector array position, and
      prism rotation angle. The shifting and broadening of both the spectral lineshape
      function and the spatial point spread function in the reconstructed hyperspectral
      imagery is compared with experimental results for monochromatic point sources.
      The shorter wavelength (lambda<500 nm) region where the prism has the highest
      spectral dispersion suffers mostly from degradation of spectral resolution in the
      presence of systematic error, while longer wavelengths (lambda>600 nm) suffer
      mostly from a shift of the spectral peaks. The quality of the reconstructed
      hyperspectral imagery is most sensitive to the misalignment of the prism rotation
      mount. With less than 1 degrees  total angular error in the two axes of freedom,
      spectral resolution was degraded by as much as a factor of 2 in the blue spectral
      region. For larger errors than this, spectral peaks begin to split into bimodal
      distributions, and spatial point response functions are reconstructed in rings
      with radii proportional to wavelength and spatial resolution.

PMID- 22858962
TI  - Multiple linear feature detection based on multiple-structuring-element center
      surround top-hat transform.
AB  - Linear feature detection is an important technique in different applications of
      image processing. To detect linear features in different types of images, a
      simple but effective algorithm based on a multiple-structuring-element center
      surround top-hat transform is proposed. The center-surround top-hat transform is
      discussed and analyzed. Based on the properties of this transform for image
      feature detection, multiple structuring elements are constructed corresponding to
      the possible linear features at different directions. The whole algorithm is
      divided into four parts. First, the algorithm uses the center-surround top-hat
      transform to detect all the possible linear features at different directions
      through constructing multiple structuring elements. Second, the detected linear
      feature regions at each direction are processed by a closing operation to remove
      the possible holes or unconnected regions. Third, the processed results of the
      detected linear feature regions at all directions are combined to form all the
      possible detected linear feature regions. Fourth, the combined result is refined
      by using some simple operations to form the final result. Experimental results on
      different types of images from different applications verified the effective
      performance of the proposed algorithm. Moreover, the experimental results
      indicate that the proposed algorithm could be used in different applications.

PMID- 22858963
TI  - Improved coupling technique of ultracompact ring resonators in silicon-on
      insulator technology.
AB  - In order to improve the coupling coefficient between a bus waveguide and a bent
      waveguide of an ultracompact microring to obtain the critical coupling, a design
      using a bent bus waveguide with reduced width is provided to maintain a better
      phase matching and increase the coupling. A full vectorial finite difference
      model, specifically suited for high index contrast and smaller size waveguides,
      for example, a waveguide in the silicon-on-insulator (SOI) technology, is
      developed. As a validation, the straight and bent waveguides are simulated using
      this model, whose results are compared with the results deduced from the
      measurement results of the ultracompact ring resonators in SOI technology. Also,
      the model solver is performed to simulate the design, and an experiment is
      implemented to testify the design.

PMID- 22858964
TI  - Wavelet power spectrum-based autofocusing algorithm for time delayed and
      integration charge coupled device space camera.
AB  - A novel autofocusing algorithm using the directional wavelet power spectrum is
      proposed for time delayed and integration charge coupled device (TDI CCD) space
      cameras, which overcomes the difficulty of focus measure for the real-time change
      of imaging scenes. Using the multiresolution and band-pass characteristics of
      wavelet transform to improve the power spectrum based on fast Fourier transform
      (FFT), the wavelet power spectrum is less sensitive to the variance of scenes.
      Moreover, the new focus measure can effectively eliminate the impact of image
      motion mismatching by the directional selection. We test the proposed method's
      performance on synthetic images as well as a real ground experiment for one TDI
      CCD prototype camera, and compare it with the focus measure based on the existing
      FFT spectrum. The simulation results show that the new focus measure can
      effectively express the defocused states for the real remote sensing images. The
      error ratio is only 0.112, while the prevalent algorithm based on the FFT
      spectrum is as high as 0.4. Compared with the FFT-based method, the proposed
      algorithm performs at a high reliability in the real imaging experiments, where
      it reduces the instability from 0.600 to 0.161. Two experimental results
      demonstrate that the proposed algorithm has the characteristics of good
      monotonicity, high sensitivity, and accuracy. The new algorithm can satisfy the
      autofocusing requirements for TDI CCD space cameras.

PMID- 22858965
TI  - Two-dimensional single-shot tomography using a virtually imaged phased array and
      a spatial phase modulator.
AB  - A virtually imaged phased array (VIPA) installed optical interferometer has been
      expanded to the two-dimensional (2D) tomography from the previous one-dimensional
      single-shot imaging technique with keeping the resolution and the measurement
      range. A single-shot measurement has been realized by a spatial phase modulator
      installed in the optical interferometer and tracing the delay time to pixel
      numbers on a 2D charge-coupled device (CCD) image sensor. The flexibility of the
      sample position was experimentally confirmed to be >25 mm, in relation to the
      VIPA coherency, for which the number of the interference order was confirmed to
      be 35. As a demonstration, a surface profile of stacked gauge blocks was
      observed. The repeatability of the surface position was 5 MUm for the surface
      profilometry. In addition, a multilayer structure was observed using a glass
      plate. The experimental resolution was 53 MUm when the amplified spontaneous
      emission light generated by the optical fiber amplifier was used for the light
      source. The single-shot measurement was confirmed by the 2D-CCD at a frame rate
      of 30 frames per second (FPS), and it provided evidence that the 2D scanless
      profilometry was successfully achieved using the VIPA optical device.

PMID- 22858966
TI  - Paraxial analysis of four-component zoom lens with fixed distance between focal
      points.
AB  - Zoom lenses with a fixed distance between focal points are analyzed. Formulas are
      derived for the primary design of basic parameters of a four-component zoom lens.
      It is also demonstrated that a three-component zoom lens can be analyzed using
      derived formulas. Zoom lenses with such a design can be used in a 4-f system with
      variable magnification or as a part of a double side telecentric lenses with
      variable magnification.

PMID- 22858967
TI  - Characteristics of composite images in multiview imaging and integral
      photography.
AB  - The compositions of images projected to a viewer's eyes from the various viewing
      regions of the viewing zone formed in one-dimensional integral photography (IP)
      and multiview imaging (MV) are identified. These compositions indicate that they
      are made up of pieces from different view images. Comparisons of the composite
      images with images composited at various regions of imaging space formed by
      camera arrays for multiview image acquisition reveal that the composite images do
      not involve any scene folding in the central viewing zone for either MV or IP.
      However, in the IP case, compositions from neighboring viewing regions aligned in
      the horizontal direction have reversed disparities, but in the viewing regions
      between the central and side viewing zones, no reversed disparities are expected.
      However, MV does exhibit them.

PMID- 22858968
TI  - Numerical analysis of astigmatism correction in gradient refractive index lens
      based optical coherence tomography catheters.
AB  - Endoscopic optical coherence tomography (OCT) catheters comprise a transparent
      tube to separate the imaging instrument from tissues. This tube acts as a
      cylindrical lens, introducing astigmatism into the beam. In this report, we
      quantified this negative effect using optical simulations of OCT catheter
      devices, and discuss possible compensation strategies. For esophageal imaging,
      the astigmatism is aggravated by the long working distance. For intracoronary
      imaging, the beam quality is degraded due to the liquid imaging environment. A
      nearly circular beam profile can be achieved by a curved focusing optics. We also
      consider the method of matching refractive indices, and it is shown to
      successfully restore a round beam.

PMID- 22858969
TI  - Binary image encryption based on interference of two phase-only masks.
AB  - Optical image encryption based on interference has attracted a lot of attention
      recently. The technique employs two pure phase masks derived from the complex
      field of the image in the Fresnel diffraction domain. The image decryption
      procedure can be carried out by inverse Fresnel transformation of the summation
      of two pure phase masks. However, the silhouette of the original image, which is
      recovered by either of the two phase-only masks, impedes the application of this
      technique. In this paper, a very simple method for binary image encryption based
      on interference of two phase-only masks is proposed without any silhouette
      problem. The binary image in combination with a random phase mask is separated
      into two phase-only masks directly, and the decryption by summation of the two
      masks can be performed digitally or optically. In this paper, the encryption and
      decryption processes are analyzed, after which both the optical simulation and
      the experimental results based on single-beam holography are given to demonstrate
      the feasibility of the encryption method. As information nowadays is mainly
      digitized into binary codes, the proposed encryption method may find applications
      in the information processing field.

PMID- 22858970
TI  - Dispersion properties of liquid-core photonic crystal fibers.
AB  - Dispersion properties of liquid-core photonic crystal fibers (PCFs) with large
      air fraction in clads between 300 to 2000 nm have been calculated by a multipole
      method for various liquids including CS(2), toluene, chloroform, and water for
      different core diameters. In calculations, air holes are assumed to be arranged
      in a regular hexagonal array in fused silica, and a central hole is filled with
      liquid to create a core. The results are compared with those obtained by a fully
      vectorial effective index method, and fitting parameters for core sizes are found
      for each liquid except for water, where the latter method does not give correct
      dispersions at short wavelengths. Also, the power ratios inside liquid cores and
      effective core areas were calculated at different wavelengths.

PMID- 22858971
TI  - Optical reversible programmable Boolean logic unit.
AB  - Computing with reversibility is the only way to avoid dissipation of energy
      associated with bit erase. So, a reversible microprocessor is required for future
      computing. In this paper, a design of a simple all-optical reversible
      programmable processor is proposed using a polarizing beam splitter, liquid
      crystal-phase spatial light modulators, a half-wave plate, and plane mirrors.
      This circuit can perform 16 logical operations according to three programming
      inputs. Also, inputs can be easily recovered from the outputs. It is named the
      "reversible programmable Boolean logic unit (RPBLU)." The logic unit is the basic
      building block of many complex computational operations. Hence the design is
      important in sense. Two orthogonally polarized lights are defined here as two
      logical states, respectively.

PMID- 22858972
TI  - Optical anemometry based on the temporal cross-correlation of angle-of-arrival
      fluctuations obtained from spatially separated light sources.
AB  - The temporal cross-correlation function of the angle-of-arrival (AOA)
      fluctuations of two optical waves propagating through atmospheric turbulence
      carries information regarding the average wind velocity transverse to the
      propagation path. We present and discuss two estimators for the retrieval of the
      path-averaged beam-transverse horizontal wind velocity, v(t). Both methods
      retrieve v(t) from the temporal cross-correlation function of AOA fluctuations
      obtained from two closely spaced light-emitting diodes (LEDs). The first method
      relies on the time delay of the peak (TDP) of the cross-correlation function, and
      the second method exploits its slope at zero lag (SZL). Over a 9 h period during
      which v(t) varied between -1.3 ms(-1) and 2.0 ms(-1), the maximum rms difference
      between optically retrieved and in situ measured 10 s estimates of v(t) was found
      to be 0.18 ms(-1) for the TDP estimator and 0.23 ms(-1) for the SZL estimator.
      Applicability and limitations of these two optical wind retrieval techniques are
      discussed.

PMID- 22858973
TI  - Accuracy of a multiple height-transfer interferometric technique for absolute
      distance metrology.
AB  - A multiple height-transfer interferometric technique was developed to increase
      the absolute distance measurement capability of a metrology system that uses a
      tunable laser. Using multiple accurately calibrated reference heights, this
      technique relaxes the requirement of knowing accurate wavelength information for
      multiple wavelength interferometry while maintaining its advantages. We present
      an uncertainty analysis, analyze the primary sources of uncertainties limiting
      the performance of this technique, and discuss how errors can be minimized.
      Measurement results of 3D images obtained from a variety of objects are
      presented. The measurement uncertainty is experimentally demonstrated to be 0.3
      MUm over 50 mm for two discontinuous surfaces with a confidence level of 95% in a
      lab environment.

PMID- 22858974
TI  - Q-switched mode-locking of an erbium-doped fiber laser using cavity modulation
      frequency detuning.
AB  - We present the results of an investigation regarding a Q-switched mode-locked
      fiber laser scheme based on a cavity modulation frequency detuning technique. The
      approach is based on undamped laser relaxation oscillations occurring due to
      frequency detuning in the fundamental cavity resonance frequency. Through a range
      of experiments with an erbium-doped, fiber-based, ring-cavity laser, this
      approach has been shown to be capable of generating high-quality Q-switched mode
      locked pulses from an optical fiber-based laser. The maximum frequency detuning
      range for a stable Q-switched mode-locking operation has been observed to vary
      depending on the pump power used. We found that the highest pulse peak power was
      obtained at the frequency detuning threshold at which the operation changed from
      the mode-locking to the Q-switched mode-locking regime.

PMID- 22858975
TI  - Fully tunable active polarization imager for contrast enhancement and partial
      polarimetry.
AB  - We present the design and the practical implementation of a polarimetric imaging
      system based on liquid-crystal modulators that allows generation and analysis of
      any polarization state on the Poincare sphere. This system is more versatile than
      standard Mueller imagers that are based on optimized, but limited, sets of
      illumination and analysis states. Examples of benefits brought by these extra
      degrees of freedom are illustrated on two different applications: contrast
      enhancement and extraction of partial polarimetric properties of a scene.

PMID- 22858976
TI  - Designs for high performance PAL-based imaging systems.
AB  - In this study, we investigate methods to optimize the design of a panoramic
      annular lens (PAL) system. The design details of a PAL surveillance system, an
      anamorphic PAL surveillance system, a phone camera with a PAL attachment, and a
      PAL endoscope system are described. All these designs are optimized using a
      standard optical software package (Zemax). The results combine very good image
      quality with a modulation transfer function above 0.3, which is within the cutoff
      frequency of sensor chips.

PMID- 22858977
TI  - Self-mixing vibrometer with real-time digital signal elaboration.
AB  - This work describes the development of an optical sensor for measurement of
      vibration without contact. The realized vibrometer is based on real-time digital
      elaboration of the signal obtained by a self-mixing interferometer, with an
      embedded autofocus system. Two different algorithms are implemented, for the
      continuous working on diffusive surfaces, with different levels of optical
      reflectivity. Thanks to the autofocus and the digital processing, the proposed
      sensor is easy to use and requires no assistance of a skilled operator.

PMID- 22858978
TI  - Simultaneous determination of thickness and refractive index based on time-of
      flight measurements of terahertz pulse.
AB  - We present a simple technique for simultaneous determination of thickness and
      refractive index of plane-parallel samples in the terahertz radiation domain. The
      technique uses time-of-flight measurements of the terahertz pulse. It has been
      employed on nine different polymers and semiconductor materials, which are
      transparent for terahertz frequencies. Our results of thickness measurement are
      in good agreement with micrometer reading. The accuracy in the determination of
      refractive index is on the order of two decimal points.

PMID- 22858979
TI  - Contouring of diffused objects using lensless Fourier transform digital moire
      holography.
AB  - A method is proposed for contouring of diffused objects using digital holographic
      moire interferometry in lensless Fourier transform configuration. Fringe
      projection moire technique combined with digital double-exposure holography
      produces the contours in this method. Two digital holograms of a 10 mm aluminum
      alloy cube are recorded by tilting the illumination angle slightly between
      exposures, and a third one is recorded by translating the detector a little
      laterally with the final illumination angle unchanged. Upon numerical processing
      of the first two holograms, a plane parallel fringe system seems to be projected
      onto the object. This fringe system can be referred to as the modified grid.
      Processing of the second and the third hologram results in another grid, the
      reference grid. In effect, processing of the first and the third hologram
      combines the modified and the reference grids to produce the moire contour
      fringes. The range of contour intervals obtained remains between 2.73 and 0.38 mm
      with seven different contours in between. The present method can measure details
      of a great variety of sizes on objects of large dimensional range. Deviations in
      the measured contour intervals from the theoretically calculated values are found
      to be within 12%-18%. This seems to be because of the deviation in the present
      experimental geometry from the ideal theoretical configuration, the hologram
      digitization, and the particular reconstruction algorithm used in the present
      experimental arrangement.

PMID- 22858980
TI  - Applied Optics growth: 1991-1999.
AB  - A commemorative editorial for the 50th anniversary of Applied Optics describes
      the journal's growth during the 1990s including internationalization of authors
      and editors as well as the rise of the Internet.

PMID- 22858981
TI  - First glimpse at a calixarene clathrate.
AB  - The 1979 X-ray crystal structure of the p-t-butylcalix[4]arene toluene 1 : 1
      intra-cavity inclusion complex proved a landmark result that established the
      iconic calixarene shape, proved the tetrameric calixarene structure and showed
      that an intrinsic molecular cavity in an artificial receptor could contain a
      guest molecule.

PMID- 22858982
TI  - Computerized assessment of placental calcification post-ultrasound: a novel
      software tool.
AB  - OBJECTIVES: Placental calcification is associated with an increased risk of
      perinatal morbidity and mortality. The subjectivity of current ultrasound methods
      of assessment of placental calcification indicates that a more objective method
      is required. The aim of this study was to correlate the percentage of
      calcification defined by the clinician using a new software tool for calculating
      the extent of placental calcification with traditional ultrasound methods and
      with pregnancy outcome. METHODS: Ninety placental images were individually
      assessed. An upper threshold was defined, based on high intensity, to quantify
      calcification within the placenta. Output metrics were then produced including
      the overall percentage of calcification with respect to the total number of
      pixels within the region of interest. The results were correlated with
      traditional ultrasound methods of assessment of placental calcification and with
      pregnancy outcome. RESULTS: The results demonstrate a significant correlation
      between placental calcification, as defined using the software, and traditional
      methods of Grannum grading of placental calcification. Whilst correlation with
      perinatal outcome and cord pH was not significant as a result of small numbers,
      patients with placental calcification assessed using the computerized software at
      the upper quartile had higher rates of poor perinatal outcome when compared with
      those at the lower quartile (8/22 (36%) vs 3/23 (13%); P = 0.069). CONCLUSION:
      These results suggest that this computerized software tool has the potential to
      become an alternative method of assessing placental calcification.

PMID- 22858983
TI  - Rotational lamellar scleral flap for the management of posttrabeculectomy bleb
      leak.
AB  - We describe a technique of rotational lamellar scleral flap for surgical repair
      in cases of posttrabeculectomy aqueous leak in patients with button holing or
      necrosis of the trabeculectomy flap. A rotational scleral flap is marked out from
      the sclera adjacent to the trabeculectomy site followed by a lamellar dissection
      to fashion the flap. Relaxing cuts are made at the base of the flap so as to
      ensure that the rotation flap adequately covers the site of aqueous leak. This
      flap is then secured to the underlying sclera and the cornea at the limbus.

PMID- 22858984
TI  - Potential resistant morphotypes of Acanthamoeba castellanii expressed in
      multipurpose contact lens disinfection systems.
AB  - OBJECTIVES: The free-living amoeba Acanthamoeba castellanii is a rare cause of
      contact lens-associated microbial keratitis. The cyst stage of this amoeba is
      noted for its resistance to disinfection by multipurpose contact lens solutions
      (MPS). This report examines and reviews the potential survival modes of A.
      castellanii in MPS. METHODS: Trophozoites of A. castellanii (ATCC 30234) at
      densities from 10 to near 10 were incubated in 3 different MPS in a laminar flow
      hood for 24 hours at ambient temperatures. The dried films of MPS and phosphate
      buffered saline (PBS) controls were examined before and after the addition of a
      peptone-yeast extract-glucose recovery broth (PYG) for the presence of amoeboid
      trophozoites and resistance stages over at least 7 days. The parallel exposure of
      trophozoites to MPS without evaporation or addition of PYG was similarly
      examined. RESULTS: Amoeboid trophozoites were not recovered in PYG nor were cyst
      like structures observed in any MPS with near 10 densities. Progressively with 10
      to 10 trophozoites, varied survival modes, particularly aggregates of
      trophozoites associated with cyst-like structures and occasional amoeboid forms
      and double-walled cysts with ostioles, became more evident. These morphotypes
      were most prominent after evaporation and typically first observed in the PYG.
      CONCLUSIONS: Trophozoites of A. castellanii near 10 and progressively to 10
      densities are capable of expressing a variety of "short-term" survival modes in
      MPS, notably with the added stress of evaporation. Expression of these alternate
      survival modes in MPS may relate, in part, to contamination of contact lens cases
      and difficulties in developing standardized MPS efficacy tests.

PMID- 22858985
TI  - Transcriptional suppression of BACH2 by the Bcr-Abl oncoprotein is mediated by
      PAX5.
AB  - Bach2 is a lymphoid-specific transcription factor with a prominent role in B-cell
      development and apoptosis-induction in response to oxidative stress. We
      previously showed that Bach2 is downregulated in chronic myeloid leukaemia (CML),
      and here we demonstrate the mechanism by which Bcr-Abl mediates this phenomenon.
      We have cloned a 3.9 Kb genomic DNA fragment upstream of the transcription
      initiation site, and delineated the core and proximal BACH2 promoter regions.
      Transient BCR-ABL expression led to significant reduction in BACH2 promoter
      activity and this effect was dependent on the kinase function of the oncoprotein.
      Sequential deletions disclosed several regulatory elements within the promoter
      region, as well as within BACH2 exonic sequences. Analysis of these elements and
      transient transfection assays led to the identification of the Pax5 transcription
      factor as a potent trans-activator of BACH2, whose effect is predominantly
      mediated through occupation of a binding site on the BACH2 promoter, as
      demonstrated by both in vitro and in vivo experiments. Overall, our data show
      that Pax5 functions as an intermediate effector in the Bcr-Abl-mediated
      transcriptional repression of BACH2. The current results, combined with previous
      reports, establish Pax5 and Bach2 as transcriptional targets of Bcr-Abl, whose
      downregulation may contribute to lymphoid blast crisis of CML.

PMID- 22858986
TI  - gamma-Catenin is overexpressed in acute myeloid leukemia and promotes the
      stabilization and nuclear localization of beta-catenin.
AB  - Canonical Wnt signaling regulates the transcription of T-cell factor (TCF)
      responsive genes through the stabilization and nuclear translocation of the
      transcriptional co-activator, beta-catenin. Overexpression of beta-catenin
      features prominently in acute myeloid leukemia (AML) and has previously been
      associated with poor clinical outcome. Overexpression of gamma-catenin mRNA (a
      close homologue of beta-catenin) has also been reported in AML and has been
      linked to the pathogenesis of this disease, however, the relative roles of these
      catenins in leukemia remains unclear. Here we report that overexpression and
      aberrant nuclear localization of gamma-catenin is frequent in AML. Significantly,
      gamma-catenin expression was associated with beta-catenin stabilization and
      nuclear localization. Consistent with this, we found that ectopic gamma-catenin
      expression promoted the stabilization and nuclear translocation of beta-catenin
      in leukemia cells. beta-Catenin knockdown demonstrated that both gamma- and beta
      catenin contribute to TCF-dependent transcription in leukemia cells. These data
      indicate that gamma-catenin expression is a significant factor in the
      stabilization of beta-catenin in AML. We also show that although normal cells
      exclude nuclear translocation of both gamma- and beta-catenin, this level of
      regulation is lost in the majority of AML patients and cell lines, which allow
      nuclear accumulation of these catenins and inappropriate TCF-dependent
      transcription.

PMID- 22858987
TI  - Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple
      Bcr-Abl inhibitors.
AB  - Grb2-associated binder 2 (Gab2) serves as a critical amplifier in the signaling
      network of Bcr-Abl, the driver of chronic myeloid leukemia (CML). Despite the
      success of tyrosine kinase inhibitors (TKIs) in CML treatment, TKI resistance,
      caused by mutations in Bcr-Abl or aberrant activity of its network partners,
      remains a clinical problem. Using inducible expression and knockdown systems, we
      analyzed the role of Gab2 in Bcr-Abl signaling in human CML cells, especially
      with respect to TKI sensitivity. We show for the first time that Gab2 signaling
      protects CML cells from various Bcr-Abl inhibitors (imatinib, nilotinib,
      dasatinib and GNF-2), whereas Gab2 knockdown or haploinsufficiency leads to
      increased TKI sensitivity. We dissected the underlying molecular mechanism using
      various Gab2 mutants and kinase inhibitors and identified the Shp2/Ras/ERK and
      the PI3K/AKT/mTOR axes as the two critical signaling pathways. Gab2-mediated TKI
      resistance was associated with persistent phosphorylation of Gab2 Y452, a PI3K
      recruitment site, and consistent with this finding, the protective effect of Gab2
      was completely abolished by the combination of dasatinib with the dual PI3K/mTOR
      inhibitor NVP-BEZ235. The identification of Gab2 as a novel modulator of TKI
      sensitivity in CML suggests that Gab2 could be exploited as a biomarker and
      therapeutic target in TKI-resistant disease.

PMID- 22858988
TI  - Predicting early spelling difficulties in children with specific language
      impairment: a clinical perspective.
AB  - This study focused on the precursors of spelling difficulties in first grade for
      children with specific language impairment (SLI). A sample of 58 second-year
      kindergartners in The Netherlands was followed until the end of first grade.
      Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal
      reasoning skills were considered as precursors, as was spelling level at an
      earlier point in time. Spelling difficulties at the end of first grade were most
      accurately identified by letter knowledge at the beginning of first grade and
      word spelling at the middle of first grade. It is concluded that spelling
      development in children with SLI can be seen as an autocatalytic process in
      which, without intervention, poor spellers generally remain poor spellers, and
      good spellers remain good spellers. A focus on early spelling intervention is
      thus emphasized.

PMID- 22858989
TI  - Chronic hepatitis B infection in adolescents who received primary infantile
      vaccination.
AB  - Hepatitis B virus (HBV) infection is a global health issue. Universal infantile
      hepatitis B (HB) vaccination is very efficacious. However, HBV infections among
      those immunized subjects have been reported. The long-term efficacy of postnatal
      passive-active HB vaccination in high-risk subjects is not well explored. A total
      of 8,733 senior high school students who were born after July 1987 were assayed
      for hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs). The
      overall HBsAg and anti-HBs-positive rates were 1.9% and 48.3%, respectively. The
      HBsAg-positive rate was 15% in HB immunoglobulin (HBIG) recipients (adjusted odds
      ratio [OR]: 15.63; 95% confidence interval [CI]: 10.99-22.22). Among students who
      did not receive HBIG, there was a significantly negative association between HB
      vaccination dosage and HBsAg-positive rate (P for trend = 0.011). Adjusted ORs
      for those who received 4, 3, and 1 to 2 doses were 1.00, 1.52 (95% CI: 0.91
      2.53), and 2.85 (95% CI: 1.39-5.81), respectively. Among HBIG recipients, the
      HBsAg-positive rate was significantly higher in subjects with maternal hepatitis
      B e antigen (HBeAg) positivity and who received HBIG off-schedule. A booster dose
      of HB vaccination was administered to 1974 HBsAg- and anti-HBs-negative subjects.
      Prebooster and a postbooster blood samples were drawn for anti-HBs
      quantification. The proportions of postbooster anti-HBs titer <10 mIU/mL was
      27.9%. Subjects with prebooster anti-HBs titers of 1.0-9.9 mIU/mL had
      significantly higher postbooster anti-HBs titers than those with prebooster anti
      HBs titers of <1.0 mIU/mL (P < 0.0001). CONCLUSION: Having maternal HBeAg
      positivity is the most important determinant for HBsAg positivity in adolescents
      who received postnatal passive-active HB vaccination 15 years before. A
      significant proportion of complete vaccinees may have lost their immunological
      memories against HBsAg.

PMID- 22858990
TI  - The effect of Cu substitution on microstructure and thermoelectric properties of
      LaCoO3 ceramics.
AB  - La(Co, Cu)O(3-delta) ceramics were prepared by pressureless sintering of citrate
      precursor powders, and their thermoelectric properties were investigated with an
      emphasis on the influence of Cu doping and phase structure as well as
      microstructure. It was found that a secondary phase first appeared in the form of
      a network along the grain boundaries and then changed to dispersion with
      increasing Cu content, which effectively reduced the lattice thermal conductivity
      of the materials. The thermal conductivity was only 1.21 W m(-1) K(-1) for the
      sample LaCo(0.75)Cu(0.25)O(3-delta), being much lower as for the thermoelectric
      oxide materials. In addition, a small amount of Cu substitution for Co increased
      the electrical conductivity greatly and the absolute Seebeck coefficient, whose
      sign was also reversed from negative to positive. The dimensionless figure of
      merit, ZT, of LaCoO(3-delta) oxides at low and middle temperatures can be
      remarkably enhanced by substituting Co with Cu.

PMID- 22858991
TI  - Cryoglobulins and multispecific antineutrophil cytoplasmic antibodies in
      propylthiouracil-induced necrotizing cutaneous vasculitis--a new association.

PMID- 22858992
TI  - Circular, nanostructured and biofunctionalized hydrogel microchannels for dynamic
      cell adhesion studies.
AB  - We report on a method to fabricate biofunctionalized polyethylene glycol hydrogel
      microchannels with adjustable circular cross-sections. The inner channel surfaces
      are decorated with Au-nanoparticle arrays of tunable density. These Au
      nanoparticles are functionalized with biomolecules whereas the hydrogel material
      provides an inert and biocompatible background. This technology provides control
      over flow conditions, channel curvature and biomolecule density on the channel
      surface. It can be applied for biophysical studies of cell-surface interactions
      mimicking, for example, leukocyte interactions with the endothelial lining in
      small vessels.

PMID- 22858994
TI  - The "golden hours" of management in acute pancreatitis.
AB  - In the past decade, a significant amount of active and enthusiastic research has
      changed the way we treat acute pancreatitis (AP) within the first 24 hours of
      presentation. We highlight the importance of rapid initiation of treatment to
      help prevent the considerable morbidity and mortality that can occur when
      interventions are delayed. We review recent data that validate simple and
      accurate tools for prognostication of AP to replace the older, more tedious
      methods that relied on numerous factors and required up to 48 hours to complete.
      Additionally, we aim to provide evidence-based guidelines and end points for
      fluid resuscitation. Finally, we hope to bring clarification to two previously
      controversial topics in AP treatment: the use of prophylactic antibiotics and
      early endoscopic retrograde cholangiopancreatography.

PMID- 22858995
TI  - Sleep disruption secondary to overnight call shifts is associated with irritable
      bowel syndrome in residents: a cross-sectional study.
AB  - OBJECTIVES: Sleep disruption has been associated with irritable bowel syndrome
      (IBS). We hypothesized that residents with greater sleep disruption secondary to
      intermittent overnight call shifts would have a higher prevalence of IBS.
      METHODS: Postgraduate residents completed a Web-based survey including
      demographic data, frequency and characteristics of call shifts, the Rome III
      questionnaire, and the IBS-quality of life measure. RESULTS: For every hour of
      sleep deprivation while on call vs. off call, the odds ratio for an increased
      likelihood of IBS was 1.32, after adjustment for age and gender. The mean number
      of calls per block, sleep deprivation while on call, and specialty program vs.
      family practice each predicted the severity of IBS. CONCLUSIONS: Sleep disruption
      secondary to overnight call in residents was associated with an increased
      prevalence of IBS.

PMID- 22858996
TI  - The digital rectal examination: a multicenter survey of physicians' and students'
      perceptions and practice patterns.
AB  - OBJECTIVES: The digital rectal examination (DRE) may be underutilized. We
      assessed the frequency of DREs among a variety of providers and explored factors
      affecting its performance and utilization. METHODS: A total of 652 faculty,
      fellows, medical residents, and final-year medical students completed a
      questionnaire about their use of DREs. RESULTS: On average, 41 DREs per year were
      performed. The yearly number of examinations was associated with years of
      experience and specialty type. Patient refusal rates were lowest among
      gastroenterology (GI) faculty and highest among primary-care doctors. Refusal
      rates were negatively correlated with comfort level of the physician in
      performing a DRE. More gastroenterologists used sophisticated methods to detect
      anorectal conditions, and gastroenterologists were more confident in diagnosing
      them. Confidence in making a diagnosis with a DRE was strongly associated with
      the number of DREs performed annually. CONCLUSIONS: The higher frequencies of
      performing a DRE, lower refusal rate, degree of comfort, diagnostic confidence,
      and training adequacy were directly related to level of experience with the
      examination. Training in DRE technique has diminished and may be lost. The DRE's
      role in medical school and advanced training curricula needs to be re
      established.

PMID- 22858997
TI  - Image of the month: Strongyloides colitis, a great mimic.

PMID- 22859000
TI  - Editorial: Body mass index and colorectal adenomas.
AB  - The recent American College of Gastroenterology Guidelines for Colorectal Cancer
      Screening highlight obese individuals as a high-risk group for colorectal cancer
      (CRC). In this issue, Okabayashi and colleagues present data from a well-designed
      and executed meta-analysis demonstrating an increased adenoma risk for a modest
      increase in body mass index (BMI). Specifically, overweight (BMI>=25) subjects
      have an increased risk for colorectal adenomas (odds ratio=1.24 (95% confidence
      interval=1.16-1.33)) as compared with non-overweight subjects. The paper's many
      strengths include the careful selection of the best studies. These data highlight
      the importance of screening in obese patients.

PMID- 22859003
TI  - Race may play a role in the clinical presentation of eosinophilic esophagitis.

PMID- 22859005
TI  - How the FDA handles GI drug safety.

PMID- 22859007
TI  - Association of intraductal papillary mucinous neoplasm (IPMN) with extra
      pancreatic cystic lesions: is there a systemic cystic disorder?

PMID- 22859008
TI  - Complete remission of protein-losing gastroenteropathy associated with Sjogren's
      syndrome by B cell-targeted therapy with rituximab.

PMID- 22859009
TI  - Mycobacterium marinum: an increasingly common opportunistic infection in patients
      on infliximab.

PMID- 22859010
TI  - Primary gastric tuberculosis mimicking gastrointestinal stromal tumor.

PMID- 22859015
TI  - Ikaros inhibits proliferation and, through upregulation of Slug, increases
      metastatic ability of ovarian serous adenocarcinoma cells.
AB  - The transcription factor Ikaros was originally found to function as a key
      regulator of lymphocyte differentiation. In this study, we provide the first
      evidence that Ikaros is expressed at higher levels in ovarian cancer tissues
      compared with normal ovarian tissues and is significantly associated with high
      FIGO stage and low differentiation state in ovarian serous adenocarcinoma. To
      this end, we transfected IK1 (full length of Ikaros) into the SKOV3 ovarian
      cancer cell line and examined cell biological behaviors including proliferation,
      migration and invasion. We found that overexpression of IK1 inhibited cell
      proliferation by inducing G1 arrest, accompanied by the upregulation of P27 and
      P21 and downregulation of cyclin D1 and D2. On the other hand, IK1 increased the
      migration and invasion of ovarian cancer cells, as assessed by scratch-wound
      assay, transwell migration assay, and invasion assay. Overexpression of IK1
      significantly increased Slug but not Snail1 expression at both mRNA and protein
      levels. It also downregulated and upregulated E-cadherin and MMP-2, two target
      genes of Slug involved in migration, respectively. Furthermore, knocking down
      Slug abrogated IK1-mediated increase in migration and invasion. These data
      suggest that Slug plays an important role in IK1-induced migration and invasion.
      In conclusion, we show for the first time that IK1 plays a dual role in the
      proliferation, migration and invasion of ovarian cancer cells, providing new
      insights into their metastasis.

PMID- 22859016
TI  - Manadoperoxides, a new class of potent antitrypanosomal agents of marine origin.
AB  - Chemical investigation of the marine sponge Plakortis cfr. lita afforded a
      library of endoperoxyketal polyketides, manadoperoxides B-K (3-5 and 7-13) and
      peroxyplakoric esters B(3) (6) and C (14). Eight of these metabolites are new
      compounds and some contain an unprecedented chlorine-bearing THF-type ring in the
      side chain. The library of endoperoxide derivatives was evaluated for in vitro
      activity against Trypanosoma brucei rhodesiense and Leishmania donovani. Some
      compounds, such as manadoperoxide B, exhibited ultrapotent trypanocidal activity
      (IC(50) = 3 ng mL(-1)) without cytotoxicity. Detailed examination of the
      antitrypanosomal activity data and comparison with those available in the
      literature for related dioxane derivatives enabled us to draw a series of
      structure-activity relationships. Interestingly, it appears that minor structural
      changes, such as a shift of the methyl group around the dioxane ring, can
      dramatically affect the antitrypanosomal activity. This information can be
      valuable to guide the design of optimized antitrypanosomal agents based on the
      dioxane scaffold.

PMID- 22859017
TI  - Prenatal ultrasound diagnosis of MYH7 non-compaction cardiomyopathy.
AB  - We report on two prenatal ultrasound diagnoses of left ventricular non-compaction
      cardiomyopathy (LVNC) associated with mutation of the cardiac beta-myosin heavy
      chain gene (MYH7). LVNC is characterized by a trabecular meshwork and deep
      intertrabecular myocardial recesses communicating with the left ventricular
      cavity. Clinical features range from non-penetrant disease in adult carriers to
      heart failure, arrhythmia and thromboembolism. Both cases showed cardiomegaly on
      prenatal ultrasound examinations, with features indicating non-compaction of the
      myocardium apparent in the third trimester. Mutations in the MYH7 gene were
      identified postnatally in each case in both the proband and the father. One
      infant underwent surgical mitral valvuloplasty and a mechanical valve implant
      later; in the other, left ventricular function was unimpaired at birth. Cardiac
      function in both cases remained stable at last follow-up. These cases highlight
      the importance of prenatal ultrasound diagnosis of LVNC and the need for
      cardiologic and molecular testing of first-degree relatives who may be unknown
      carriers of an MYH7 mutation.

PMID- 22859018
TI  - Psychological entitlement and abusive supervision: political skill as a self
      regulatory mechanism.
AB  - BACKGROUND: Abusive supervision in the workplace is steadily increasing. Such
      behavior has been linked to a host of negative individual and organizational
      consequences. In a health care environment particularly, such behavior can have
      detrimental effects. PURPOSES: This study advances self-regulation theory by
      framing the entitlement-abusive supervision relationship in terms of a motive to
      obtain resources via a behavior that is not socially sanctioned. Furthermore, we
      argue that political skill serves as a self-regulating mechanism that reduces the
      motivation to secure personal resources through abusive behavior.
      METHODOLOGY/APPROACH: Our hypotheses were tested using a sample of nurses and
      their supervisors who were asked to complete a survey. A final sample of 132
      supervisor-subordinate dyads was obtained. FINDINGS: Analysis suggests that
      supervisors high in psychological entitlement are more likely to be perceived by
      their subordinates as abusive. Political skill, however, moderated this
      relationship by serving as a regulatory mechanism that thwarts entitled
      supervisors from engaging in abusive behaviors. PRACTICE IMPLICATIONS: Our
      findings underscore the common concern that entitlement and abuse can be harmful
      for organizations. Entitled supervisors who are high in political skill may
      recognize that engaging in less aggressive influence behaviors may be more
      effective in achieving self-serving motives. Consequently, health care
      organizations need to be proactive in order to reduce entitlement and prevent
      abusive behaviors in the workplace.

PMID- 22859020
TI  - Old and new ways to study characteristics of reading disability: the case of the
      nonword-reading deficit.
AB  - Theoretical and computational models of reading have traditionally been informed
      by specific characteristics of disabled readers. One of the most frequently
      studied marker effects of developmental dyslexia is the nonword-reading deficit.
      Disabled readers are generally believed to show a specific problem in reading
      nonwords. This study presents a survey of frequently cited methods used to
      examine this effect by controlling general reading ability in various ways. An
      extensive analysis, however, shows that the majority of these methods (grade
      equivalents scores, the reading-level match design, and interactions in a
      chronological-age match design) actually fail to account for confounding
      variables such as age and general slowing, potentially affecting the conclusions
      reached. To alleviate this problem, an alternative method is presented: i.e.
      state trace analysis. Applying this method in a sample of Dutch disabled and
      typical readers, the results revealed an absence of a nonword-reading deficit in
      the disabled readers. Furthermore, after controlling for their decoding ability,
      disabled readers showed inferior word reading performance, which strongly
      suggests that the fundamental problem of disabled readers does not relate to the
      reading of nonwords but concerns their (dis)ability to acquire orthographic (word
      specific) knowledge. Further, predictions for disabled readers in an inconsistent
      orthography like English are formulated. Finally, based on a review of
      neurobiological studies, implications for theories of reading disability are
      discussed.

PMID- 22859019
TI  - Causal imprinting in causal structure learning.
AB  - Suppose one observes a correlation between two events, B and C, and infers that B
      causes C. Later one discovers that event A explains away the correlation between
      B and C. Normatively, one should now dismiss or weaken the belief that B causes
      C. Nonetheless, participants in the current study who observed a positive
      contingency between B and C followed by evidence that B and C were independent
      given A, persisted in believing that B causes C. The authors term this difficulty
      in revising initially learned causal structures "causal imprinting." Throughout
      four experiments, causal imprinting was obtained using multiple dependent
      measures and control conditions. A Bayesian analysis showed that causal
      imprinting may be normative under some conditions, but causal imprinting also
      occurred in the current study when it was clearly non-normative. It is suggested
      that causal imprinting occurs due to the influence of prior knowledge on how
      reasoners interpret later evidence. Consistent with this view, when participants
      first viewed the evidence showing that B and C are independent given A, later
      evidence with only B and C did not lead to the belief that B causes C.

PMID- 22859021
TI  - DFT study on the mechanism of water-assisted dihydrogen elimination in group 6
      octahedral metal hydride complexes.
AB  - The reaction of water with octahedral bis-, tris- and tetrakis
      (phosphine)tungsten, (phosphine)molybdenum and (phosphine)chromium complexes has
      been studied using B3LYP/def2-TZVPP level of DFT to elucidate dissociative,
      associative and hydride migratory insertion mechanisms for hydrogen elimination.
      In the dissociative mechanism, phosphine dissociation requires 19.3-28.5 kcal
      mol(-1) of energy. The phosphine-water ligand exchange is endergonic due to poor
      coordination ability of water to group 6 metals (binding energy 8.8-15.5 kcal
      mol(-1)). The ligand exchange leads to intermolecular M-H...H(2)O dihydrogen
      interaction and facilitates dihydrogen elimination (G(act) = 6.8-15.5 kcal mol(
      1)). In the associative mechanism, a water molecule in the first solvation shell
      interacts with the M-H bond through a dihydrogen bond (interaction energy 2.7-4.0
      kcal mol(-1)) and leads to the elimination of H(2) by forming a hydroxide
      complex. Compared to the dissociative mechanism, G(act) of associative mechanisms
      are ~22 kcal mol(-1) higher. In the hydride migratory insertion mechanism, the
      hydride ligand shifts to the CO ligand (G(act) = 25.4-30.4 kcal mol(-1)) to
      afford a formyl complex and subsequently the H-H bond coupling occurs between
      formyl and water ligand (G(act) = 2.8-4.4 kcal mol(-1)). In many cases, the
      migratory insertion mechanism can simultaneously operate with the dissociative
      mechanism as a minor pathway, whereas owing to high G(act) value, the associative
      mechanism can be described as inactive in the reaction. The general argument that
      dihydrogen elimination is preceded by the formation of a dihydrogen intermediate
      is not applicable for the systems studied herein as the most favoured
      dissociative mechanism does not pass through such an intermediate. On the other
      hand, irrespective of the mechanisms, dihydrogen elimination invariably occurs
      with the formation of a dihydrogen bonded transition state. Our results also
      suggest that group 6 octahedral metal hydride complexes are attractive targets
      for the design of water splitting reactions.

PMID- 22859022
TI  - Color code identification in coded structured light.
AB  - Color code is widely employed in coded structured light to reconstruct the three
      dimensional shape of objects. Before determining the correspondence, a very
      important step is to identify the color code. Until now, the lack of an effective
      evaluation standard has hindered the progress in this unsupervised
      classification. In this paper, we propose a framework based on the benchmark to
      explore the new frontier. Two basic facets of the color code identification are
      discussed, including color feature selection and clustering algorithm design.
      First, we adopt analysis methods to evaluate the performance of different color
      features, and the order of these color features in the discriminating power is
      concluded after a large number of experiments. Second, in order to overcome the
      drawback of K-means, a decision-directed method is introduced to find the initial
      centroids. Quantitative comparisons affirm that our method is robust with high
      accuracy, and it can find or closely approach the global peak.

PMID- 22859023
TI  - Interferometric laser imaging for droplet sizing revisited: elaboration of
      transfer matrix models for the description of complete systems.
AB  - We report the development of an interferometric laser imaging for droplet sizing
      (ILIDS) numerical simulator. It is based on the use of generalized Huygens
      Fresnel integrals associated to transfer matrices that describe the whole imaging
      setup. This simulator allows easy simulation of any kind of ILIDS setup.
      Simulations are shown to be in good agreement with experimental results. This
      simulator offers important perspectives in the design, realization, and
      calibration of ILIDS instruments, as airborne instruments, or in situ
      measurements in flows.

PMID- 22859024
TI  - Automatically obtaining the correspondences of four coplanar points for an
      uncalibrated camera.
AB  - For an uncalibrated camera, the problem of automatically determining the
      correspondences of four given coplanar points has not yet been solved. Previous
      algorithms [mostly related to two-dimensional (2D) homography] avoided this
      correspondence problem and required people to manually choose the correct image
      point one by one. In this paper, we propose a novel three-step method to
      automatically identify the correct correspondence. First, prejudge the
      possibilities of correspondences (PoC) based on the analysis of why ambiguous
      correspondences occur. Second, set a cuboid bound for the optical center to
      verify if the center circle computed from the homography intersects it. Third,
      utilize the reasonability and stability of the intrinsic parameters to remove the
      still-wrong PoC. Besides applications in recovering 2D Euclidean structure and
      camera calibration, we can also extend the proposed method to detect multiple
      quadrangle objects, no matter if they are coplanar or not. Many experiments with
      simulated and real data show that our method has good performance and important
      applied value.

PMID- 22859025
TI  - Asymmetric color cryptosystem using polarization selective diffractive optical
      element and structured phase mask.
AB  - A single channel asymmetric color image encryption scheme is proposed that uses
      an amplitude- and phase- truncation approach with interference of polarized
      wavefronts. Instead of commonly used random phase masks, wavelength-dependent
      structured phase masks (SPM) are used in the fractional Fourier transform domain
      for image encoding. The primary color components bonded with different SPMs are
      combined into one grayscale image using convolution. We then apply the amplitude
      and phase truncation to the fractional spectrum, which helps generate unique
      decryption keys. The encrypted image bonded with a different SPM is then encoded
      into a polarization selective diffractive optical element. The proposed scheme
      alleviates the alignment problem of interference and does not need iterative
      encoding and offers multiple levels of security. The effect of a special attack
      to the proposed asymmetric cryptosystem has been studied. To measure the
      effectiveness of the proposed method, we calculated the mean square error between
      the original and the decrypted images. The computer simulation results support
      the proposed idea.

PMID- 22859026
TI  - Observation of non-principal plane neutral points in the upwelling polarized
      light field above a water surface.
AB  - Using a digital camera and linearly polarizing film, we have developed a method
      for observing neutral point locations in the natural light field of the
      atmosphere. Utilizing this method, we have observed neutral points in the
      upwelling light field above a water surface. We report the location of these
      neutral points and compare them to Monte Carlo simulations.

PMID- 22859027
TI  - Characterization of a visible spectrum division-of-focal-plane polarimeter.
AB  - The development of high resolution division-of-focal-plane polarimeters in the
      visible spectrum allows real-time capture of two chief properties of interest,
      the degree of linear polarization and the angle of polarization. The accuracy of
      these two parameters can be influenced by a number of factors in the imaged
      scene, from the incident intensity and wavelength to the lens used for image
      capture. The alignment, transmission, and contrast ratios of the pixel matched
      filters also impact the measured parameters. A system of measurements is
      presented here that shows how these factors can determine the quality of a
      division-of-focal-plane polarimeter.

PMID- 22859028
TI  - Narrowband sodium lidar for the measurements of mesopause region temperature and
      wind.
AB  - We report here a narrowband high-spectral resolution sodium temperature/wind
      lidar recently developed at the University of Science and Technology of China
      (USTC) in Hefei, China (31.5  degrees N, 117  degrees E). Patterned after the
      Colorado State University (CSU) narrowband sodium lidar with a dye laser-based
      transmitter, the USTC sodium temperature/wind lidar was deployed with a number of
      technical improvements that facilitate automation and ease of operation; these
      include a home constructed pulsed dye amplifier (PDA), a beam-steering system, a
      star-tracking program, and an electronic timing control. With the averaged power
      of ~1.2 W output from PDA and the receiving telescope diameter of 0.76 m, our
      lidar system has a power aperture product of ~0.55 Wm(2) and is comparable to the
      CSU and the University of Illinois at Urbana-Champaign (UIUC) sodium lidar
      systems. The uncertainties of typical measurements induced by photon noise and
      laser locking fluctuation for the temperature and wind with a 2 km vertical and
      15 min temporal resolutions under the nighttime clear sky condition are estimated
      to be ~1.0 K and ~1.5 m/s, respectively, at the sodium peak (e.g., 91 km), and 8
      K and 10 m/s, respectively, at both sodium layer edges (e.g., 81 km and 105 km).
      The USTC narrowband sodium lidar has been operated regularly during the night
      since November 2011. Using the initial data collected, we demonstrate the
      reliability and suitability of these high resolution and precision datasets for
      studying the wave perturbations in the mesopause region.

PMID- 22859029
TI  - Frequency spurious aversion by minimal reverse bias selection of a high-speed
      optically triggered sampling circuit based on a positive-intrinsic-negative
      photodiode.
AB  - In this paper we present a procedure for the selection of the minimal dc reverse
      bias voltage of a high-speed optically triggered sampling circuit. The optically
      triggered sampling circuit is based on a PIN photodiode. A set of expressions
      that includes the optical power dependence of the current passing through the PIN
      photodiode is derived. Theoretical results of the procedure are experimentally
      verified with practical measurements obtained from a 3 giga samples per second
      (GS/s) and a 20 GS/s sampling circuit implemented with commercial PIN
      photodiodes. Reductions in the signal-to-noise and distortion ratio of 37.28 and
      6.9 dBs, as well as increments in the spurious free dynamic range of 31 and 19
      dBs in the sampled signals, are respectively averted by the selection of the
      minimal reverse bias.

PMID- 22859030
TI  - Curved focal plane detector array for wide field cameras.
AB  - Miniaturization is the main goal for system design in future cameras. This paper
      offers a novel method to scale down the optical system and to improve the image
      quality. As with the human retina, the detector array is spherically bent to fit
      the curved image surface; so the field curvature aberration is directly
      suppressed, leading to a better resolution and a simplified optical design. By
      thinning the substrate, the device is monolithically curved without modifying the
      fabrication process of the active pixels. Optical characterizations have been
      performed on planar and curved focal plane based cameras to illustrate the
      optical advantages of detector array curvature.

PMID- 22859031
TI  - Reflectance reduction of InP wafers after high-temperature annealing.
AB  - Broadband reduction of light reflection from the surface of InP wafers after high
      temperature annealing in air has been observed. In the transparency region of the
      material, the reflection drop is accompanied by increasing transmission of light
      through the wafer. The spectral position of a deep minimum of the reflection
      coefficient can be tuned, by varying the temperature and the time of annealing,
      in a wide spectral range from ultraviolet to infrared. The effect is due to
      formation of thermal oxide layers on the surfaces of the wafer with optical
      parameters favorable for antireflection.

PMID- 22859032
TI  - Three-photon absorption and nonlinear refraction of BaMgF4 in the ultraviolet
      region.
AB  - The nonlinear refraction and nonlinear absorption phenomena are investigated in
      BaMgF(4) single crystal using the Z-scan technique in the ultraviolet region with
      a pulsed laser at 400 nm with 1 ps pulse duration. The remarkable nonlinear
      absorption behavior is identified to be three-photon absorption under the
      experimental conditions. In addition, both nonlinear refraction and nonlinear
      absorption have relatively large values and possess small anisotropy along three
      different crystallographic axes. The large values of nonlinear refractive index
      are demonstrated through the self-phase modulation effect.

PMID- 22859033
TI  - Raman spectral analysis of TiO2 thin films doped with rare-earth samarium.
AB  - TiO(2) thin films doped with rare-earth samarium were prepared on a quartz plate
      by the sol-gel/spin-coating technique. The samples were annealed at 700  degrees
      C to 1100  degrees C, and the Raman spectra of the samples were obtained.
      Analyses of Raman spectra show that samarium doping can inhibit the anatase
      rutile phase transition. Samarium doping can refine grains of TiO(2) thin films
      and increase the internal stress, thereby preventing lattice vibration.
      Nanocrystalline TiO(2) thin films obviously show the phonon confinement effect,
      i.e., the blueshift of characteristic Raman peak and full width at half-height
      increase, and the peak shapes asymmetrically broaden with a decrease in the grain
      sizes of the samples.

PMID- 22859034
TI  - Concurrent three-dimensional characterization of the refractive-index and
      residual-stress distributions in optical fibers.
AB  - A three-dimensional index-stress distribution (3DISD) measurement method for
      determining concurrently the refractive-index distributions (RIDs) and residual
      stress distributions (RSDs) in optical fibers is presented. The method combines
      the quantitative-phase microscopy technique, the Brace-Kohler compensator
      technique, and computed tomography principles. These techniques are implemented
      on a common apparatus to enable concurrent characterization of the RID and the
      RSD. Measurements are performed on Corning SMF-28 fiber in an unperturbed section
      and in a section exposed to CO(2) laser radiation. The concurrent measurements
      allow for the first accurate comparison of the collocated RID and RSD. The
      resolutions of the refractive index and stress are estimated to be 2.34*10(-5)
      and 0.35 MPa, respectively.

PMID- 22859035
TI  - Tiling integral floating display system with optimized viewing window.
AB  - A tiling integral floating display system is proposed using the optimization of
      viewing window. The integral floating display, which is a combination of an
      integral imaging system and a floating lens, has many advantages, but it is hard
      to realize a large system due to the cost and difficulties in making the large
      floating device. In this paper, the stackable integral floating display is
      proposed by modifying the size of the viewing window to be the same as that of
      the display device, which can be a solution for the large scale autostereoscopic
      three-dimensional display system.

PMID- 22859036
TI  - Free of reabsorption upper-state lifetime measurements by the method of transient
      gratings.
AB  - Light reabsorption and radiation trapping can noticeably distort fluorescence
      decay in solid-state laser gain media with a partial overlap of absorption and
      emission bands. In this paper, the upper-state lifetime measurements in laser
      materials by the method of transient gratings are discussed. A theoretical model
      for description of reabsorption in a thin layer is developed. It is shown that
      under certain conditions reabsorption has no effect on the transient time of
      refractive index grating and thus the true upper-state lifetime can be measured.
      Some experimental results confirming effectiveness of the technique are
      presented.

PMID- 22859037
TI  - Temperature measurements in a rapid compression machine using mid-infrared H2O
      absorption spectroscopy near 7.6 MUm.
AB  - A method for measuring the temporal temperature and number density in a rapid
      compression machine (RCM) using quantum cascade laser absorption spectroscopy
      near 7.6 MUm is developed and presented in this paper. The ratios of H(2)O
      absorption peaks at 1316.55 cm(-1) and 1316.97 cm(-1) are used for these
      measurements. In order to isolate the effects of chemical reactions, an inert
      mixture of argon with 2.87% water vapor is used for the present investigation.
      The end of compression pressures and temperatures in the RCM measurements are
      P(C)=10, 15, and 20 bar in the range of T(C)=1000 to 1200 K. The measured
      temperature history is compared with that calculated based on the adiabatic core
      assumption and is found to be within +/-5 K. The measured temporal number density
      of H(2)O to an accuracy of 1%, using the absolute absorption of the two
      rovibrational lines, show that the mixture is highly uniform in temperature. A
      six-pass, 5.08 cm Herriott cell is used to calibrate the line strengths in air
      and broadening in an Ar bath gas.

PMID- 22859038
TI  - Remote sensing of seawater and drifting ice in Svalbard fjords by compact Raman
      lidar.
AB  - A compact Raman lidar system for remote sensing of sea and drifting ice was
      developed at the Wave Research Center at the Prokhorov General Physics Institute
      of the Russian Academy of Sciences. The developed system is based on a diode
      pumped solid-state YVO(4):Nd laser combined with a compact spectrograph equipped
      with a gated detector. The system exhibits high sensitivity and can be used for
      mapping or depth profiling of different parameters within many oceanographic
      problems. Light weight (~20 kg) and low power consumption (300 W) make it
      possible to install the device on any vehicle, including unmanned aircraft or
      submarine systems. The Raman lidar presented was used for study and analysis of
      the different influence of the open sea and glaciers on water properties in
      Svalbard fjords. Temperature, phytoplankton, and dissolved organic matter
      distributions in the seawater were studied in the Ice Fjord, Van Mijen Fjord, and
      Rinders Fjord. Drifting ice and seawater in the Rinders Fjord were characterized
      by the Raman spectroscopy and fluorescence. It was found that the Paula Glacier
      strongly influences the water temperature and chlorophyll distributions in the
      Van Mijen Fjord and Rinders Fjord. Possible applications of compact lidar systems
      for express monitoring of seawater in places with high concentrations of floating
      ice or near cold streams in the Arctic Ocean are discussed.

PMID- 22859039
TI  - Lensless phase microscopy using phase retrieval with multiple illumination
      wavelengths.
AB  - A phase retrieval method for microscopy using multiple illumination wavelengths
      is proposed. A fast algorithm suitable for calculations with high numerical
      aperture is used for the iterative retrieval of the object wavefront. The
      advantages and limitations of the technique are systematically analyzed and
      demonstrated by both simulation and experimental results.

PMID- 22859040
TI  - Compact and robust method for full Stokes spectropolarimetry.
AB  - We present an approach to spectropolarimetry that requires neither moving parts
      nor time dependent modulation, and that offers the prospect of achieving high
      sensitivity. The technique applies equally well, in principle, in the optical,
      UV, or IR. The concept, which is one of those generically known as channeled
      polarimetry, is to encode the polarization information at each wavelength along
      the spatial dimension of a two-dimensional data array using static, robust
      optical components. A single 2D data frame contains the full polarization
      information and can be configured to measure either two or all of the Stokes
      polarization parameters. By acquiring full polarimetric information in a single
      observation, we simplify polarimetry of transient sources and in situations where
      the instrument and target are in relative motion. The robustness and simplicity
      of the approach, coupled with its potential for high sensitivity, and
      applicability over a wide wavelength range, is likely to prove useful for
      applications in challenging environments such as space.

PMID- 22859041
TI  - Wavenumber scanning-based Fourier transform white-light interferometry.
AB  - Fourier transform white-light interferometry recovers the optical path difference
      of an interferometer by measuring the phase change caused by scanning wavelength.
      However, the optical spectrum, obtained by wavelength scanning method (lambda
      method), contains a chirp in period. The chirp would induce deviation and
      decrease the measurement accuracy. An improved method, the wavenumber scanning
      method (k-method), is proposed and experimentally demonstrated, in which there is
      no chirp in the optical spectrum. The measurement results using the k-method and
      the lambda-method are compared experimentally. The experimental results show that
      the standard deviation of the measurement results decreases from 0.015 to 0.004
      MUm, when an extrinsic Fabry-Perot interferometer with a cavity length of 387 MUm
      is interrogated.

PMID- 22859042
TI  - Calibrating an interferometric laser frequency stabilization to megahertz
      precision.
AB  - We report on a calibration procedure that enhances the precision of an
      interferometer based frequency stabilization by several orders of magnitude. For
      this purpose, the frequency deviations of the stabilization are measured
      precisely by means of a frequency comb. This allows us to implement several
      calibration steps that compensate different systematic errors. The resulting
      frequency deviation is shown to be less than 5.7 MHz (rms 1.6 MHz) in the whole
      wavelength interval 750-795 nm. Wide tuning of a stabilized laser at this
      exceptional precision is demonstrated.

PMID- 22859043
TI  - Force mapping of an optical trap using an acousto-optical deflector in a time
      sharing regime.
AB  - We suggest and study experimentally a time-sharing protocol for acousto-optical
      deflectors (AODs) that permits one to map the radial optical trapping force of
      optical tweezers without using a controllable flux control or an additional beam.
      Variations of the trapping potential due to modifications of the optical system
      are easily detected in terms of the force map. The protocol can be used in
      optical tweezers that already include an AOD without adding new elements in the
      existing optical system.

PMID- 22859044
TI  - High-power tunable narrow-linewidth Ti:sapphire laser at repetition rate of 1
      kHz.
AB  - We report a high-power tunable narrow-bandwidth Ti:sapphire laser at a repetition
      rate of 1 kHz. The spectral linewidth of 0.4 pm with wavelength tuning range from
      780 nm to 820 nm is obtained by a spectrum-compressing technique that consists of
      one grating and four fused silica prisms in the oscillator cavity. This narrow
      bandwidth seed from the oscillator is further amplified to 6.5 W with pulse
      duration of 16 ns under the pumper power of 22 W. This high-power laser with
      narrow linewidth is candidate for isotope separation and accuracy spectrum
      analysis.

PMID- 22859045
TI  - Demonstrated resolution enhancement capability of a stripmap holographic aperture
      ladar system.
AB  - Holographic aperture ladar (HAL) is a variant of synthetic aperture ladar (SAL).
      The two processes are related in that they both seek to increase cross-range
      (i.e., the direction of the receiver translation) image resolution through the
      synthesis of a large effective aperture. This is in turn achieved via the
      translation of a receiver aperture and the subsequent coherent phasing and
      correlation of multiple received signals. However, while SAL imaging incorporates
      a translating point detector, HAL takes advantage of a two-dimensional
      translating sensor array. For the research presented in this article, a side
      looking stripmap HAL geometry was used to sequentially image a set of Ronchi
      ruling targets. Prior to this, theoretical calculations were performed to
      determine the baseline, single subaperture resolution of our experimental,
      laboratory-based system. Theoretical calculations were also performed to
      determine the ideal modulation transfer function (MTF) and expected cross-range
      HAL image sharpening ratio corresponding to the geometry of our apparatus. To
      verify our expectations, we first sequentially captured an oversampled collection
      of pupil plane field segments for each Ronchi ruling. A HAL processing algorithm
      incorporating a high-precision speckle field registration process was then
      employed to phase-correct and reposition the field segments. Relative interframe
      piston phase errors were also removed prior to final synthetic image formation.
      By then taking the Fourier transform of the synthetic image intensity and
      examining the fundamental spatial frequency content, we were able to produce
      experimental modulation transfer function curves, which we then compared with our
      theoretical expectations. Our results show that we are able to achieve nearly
      diffraction-limited results for image sharpening ratios as high as 6.43.

PMID- 22859046
TI  - On the reliability of reverse engineering results.
AB  - Determination of actual parameters of manufactured optical coatings (reverse
      engineering of optical coatings) provides feedback to the design-production chain
      and thus plays an important role in raising the quality of optical coatings
      production. In this paper, the reliability of reverse engineering results
      obtained using different types of experimental data is investigated. Considered
      experimental data include offline normal incidence transmittance data, offline
      ellipsometric data, and online transmittance monitoring data recorded during
      depositions of all coating layers. Experimental data are obtained for special
      test quarter-wave mirrors with intentional errors in some layers. These mirrors
      were produced by a well-calibrated magnetron-sputtering process. The intentional
      errors are several times higher than estimated errors of layer thickness
      monitoring, and the reliability of their detection is used as a measure of
      reliability of reverse engineering results. It is demonstrated that the most
      reliable results are provided by online transmittance data.

PMID- 22859047
TI  - Second-order derivatives of optical path length of ray with respect to variable
      vector of source ray.
AB  - A method is proposed for determining the second-order derivatives (i.e., the
      Hessian matrix) of the optical path length of a ray with respect to the variable
      vector of the source ray in an optical system comprising both flat and spherical
      boundary surfaces. Several wavefront aberration problems are investigated using
      the Hessian matrix proposed in this study and the Jacobian (first-order
      derivatives) matrix presented in the literature. It is found that when using the
      Hessian matrix the precision of wavefront aberration is significantly improved
      when evaluated up to the quadratic term of the Taylor series expansion. The
      methodology proposed in this study not only provides the means to investigate the
      principal curvatures of the wavefront along a ray, but also yields the
      information required to determine the irradiance and caustics of both
      axisymmetric and nonaxisymmetric optical systems.

PMID- 22859048
TI  - Optimized thermal design of new reflex LED headlamp.
AB  - This paper focuses on the heat dissipation efficiency issues in LED headlamps.
      The cooling structure is designed and built in Ansys-icepak software based on
      computational fluid dynamics. During optimized simulation of a single model,
      geometric parameters, maximum temperature, and thermal resistance are taken as
      variables, constraint, and objective, respectively. In the case of 85  degrees C,
      the optimized model has mass of 0.28 kg, maximum temperature rise of 12.52 
      degrees C, and thermal resistance of 1.03  degrees C/W. During the design of the
      headlamp, air inlet and outlet are arranged, respectively, taking advantage of
      airflow generated from the moving auto. The maximum temperature rise is 6.5 
      degrees C lower than that in closed case at the speed of 2 m/s.

PMID- 22859049
TI  - Method to test rotationally asymmetric surface deviation with high accuracy.
AB  - We have proposed a new absolute method to test rotationally asymmetric surface
      deviation. Relying on the high accuracy of Zernike polynomial fitting with least
      squares algorithm for the low-frequency component and preserving the high
      frequency component with the averaging method, the new method can guarantee the
      high accuracy of the measurement result with fewer rotational measurements
      compared to the traditional multiangle averaging method. It realizes a balance
      between the accuracy and efficiency of the measurements. It has been verified by
      experiments; the root mean square (rms) of residual figure between the two
      methods is ~0.6 nm. Meanwhile, the new method can suppress environmental noise
      introduced in measurement results well.

PMID- 22859050
TI  - Waveguiding properties in Yb:YAG crystals implanted with protons and carbon ions.
AB  - We report the fabrication and analysis of optical waveguides in Yb:YAG crystals
      using either proton or carbon ion implantation. Planar waveguides were obtained
      by implanting the whole surface of the crystals. Channel waveguides were defined
      using an electroformed mask with apertures of 10, 15, and 20 micrometers in
      width. The waveguiding properties of the structures were analyzed, showing good
      light confinement based on the transversal mode distribution and optical
      transmission measurements. The spectroscopic properties of the Yb ions in the YAG
      host are preserved after the implantation process, which demonstrates the
      potential of this technique for tailoring microcomponents for integrated optics
      applications. In particular, the Yb:YAG waveguides have the potential to operate
      as miniature lasers.

PMID- 22859051
TI  - High efficiency terahertz-wave photonic crystal fiber optical parametric
      oscillator.
AB  - We theoretically propose phase matched terahertz (THz)-wave generation via
      degenerate four-wave mixing (FWM) in a fiber optical parametric oscillator (FOPO)
      with our newly designed photonic crystal fiber (PCF). Perfect phase matching is
      realized when we locate the pump wavelength in the normal group-velocity
      dispersion (GVD) regime. The generated THz-wave can be tuned from 4.7578 to
      5.9015 THz by varying the pump wavelength. Moreover, peak power of 27.38 W at
      5.9015 THz with conversion efficiency of 1.37% is realized when the pump peak
      power of 2000 W is at 4.675 MUm in our FOPO.

PMID- 22859052
TI  - Long-haul dense wavelength division multiplexing between a chaotic optical secure
      channel and a conventional fiber-optic channel.
AB  - The purpose of this paper is to numerically investigate dense wavelength division
      multiplexing (DWDM) transmission between a chaotic optical secure channel and a
      conventional fiber-optic channel. A 2.5 Gbits/s secure message masked by the
      chaotic optical secure channel and a 10 Gbits/s message sequence carried by the
      conventional fiber-optic channel can be realized simultaneously when the channel
      spacing is 0.8 nm. The results show that the Q-factors of the recovered messages
      can be increased significantly when the launched optical power is reduced
      appropriately. The deterioration of the quality of communication caused by fiber
      dispersion can be compensated noticeably on the condition that the symmetrical
      dispersion compensation scheme is adopted. In addition, the secure message is
      masked by chaos shift keying in the chaotic optical secure channel. The
      multiplexing distance between the chaotic optical secure channel and the
      conventional fiber-optic channel is up to 500 km.

PMID- 22859053
TI  - Mode selection in an ultralarge ring laser gyro.
AB  - A significant operational difficulty with very large ring laser gyroscopes is the
      length of time required to achieve the desired single-mode configuration. A
      control technique has been developed where the order of mode splitting between
      corotating beams is alternated. Theoretical advantages to this are the
      elimination of noise caused by variations in perimeter and systematic error
      caused by Adler pulling. External seeding of mode configurations has been
      proposed to allow the technique to work fast enough to eliminate known sources of
      perimeter perturbations. While investigating the intensity requirements for this
      concept, we found that the operating mode of a large ring laser can be
      successfully self-seeded with seed beams of near (6+/-3) single photon cavity
      mode population.

PMID- 22859055
TI  - Polyimido sulfur anions and ylides.
AB  - Isovalent electronic replacement of the oxygen atoms in the classic SO(n)(m-)
      molecules and ions by NR imido groups yields the polyimido sulfur species
      S(NR)(n)(m-), n = 2, 3, 4 and m = 0, 2. The crucial cornerstone to the richness
      of SN chemistry is the access to sulfur diimides S(NR)(2) and triimides S(NR)(3).
      While the syntheses of the first are well established the preparations of the
      second were hazardous and of poor yields. A new facile, safe and elaborated route
      to give quantitative yields is presented. It involves the synthesis of triimido
      sulfites S(NR)(3)(2-), which are versatile ligands in their own right. With a
      trigonal pyramidal shape, containing three basal negatively charged nitrogen
      atoms, they are rare examples of dianionic tripodal ligands. Various (mixed)
      metal complexes are presented. Lithium coordination at the N-S-N bisections
      converts the dianion into the inverse tripod ligand Li(3)(NR)(3)S(+), capable of
      anion solvation. Among others, this motif stabilizes unprecedented monomeric
      methyllithium and lithium enolate. In the reaction of sulfur diimides S(NR)(2)
      and triimides S(NR)(3) with organometallics the diimidosulfinates RS(NR)(2)(-)
      and triimidosulfonates RS(NR)(3)(-) are synthesised. Both display a rich
      coordination chemistry to various metals, which is discussed in the review.
      Furthermore, the S-organo substituent can be modified in various ways. It can be
      a linker between two SN moieties or can be shaped to a R(2)N- or R(2)P-donating
      side arm of any form or length to give hemilabile scorpionates. Their ample
      application in metal coordination and anion solvation is presented. These
      monoanions can be converted to the related ylides by deprotonation of the S-alkyl
      group. The diimidosulfur(IV) ylides (R(2)C)S(NR)(2)(2-) and triimidosulfur(VI)
      ylides (R(2)C)S(NR)(3)(2-) contain the CR(2) methylene group, isoelectronic to
      the NR imido group. Their coordination behaviour and reactivity are discussed. In
      addition to the rich SN chemistry the S-N and S-C bonding is elucidated by means
      of theoretical and experimental charge density investigations and topological
      analyses on the basis of multipole refinement. As the most important result
      hypervalency at sulfur and S=N(C) double bonding are ruled out as superfluous
      concepts.

PMID- 22859054
TI  - Prevalence and clinical profile of vitiligo in China: a community-based study in
      six cities.
AB  - Vitiligo is a common skin disease, the prevalence of which varies between races
      and countries. In China, no population-based study has been reported, although
      there have been some epidemiological studies on single cities or regions. The
      objective of this study was to obtain the prevalence and clinical profile of
      vitiligo in China. The study was conducted in 6 cities. Cluster sampling was used
      in selecting communities. Residents were visited at home and were asked to
      complete questionnaires and receive dermatological examinations. A total of
      19,974 residents were visited and 17,345 valid questionnaires were obtained. The
      overall prevalence of vitiligo was 0.56%. Men were affected more than women
      (0.71% vs. 0.45%, p < 0.01). The prevalence of vitiligo increased with age. The
      most common type was focal vitiligo (36.1%). A positive family history was found
      in 9.8% of patients. Thirty-two percent of patients reported a negative impact of
      vitiligo on their quality of life.

PMID- 22859056
TI  - The bulk and the gas phase of 1-ethyl-3-methylimidazolium ethylsulfate:
      dispersion interaction makes the difference.
AB  - Ab initio molecular dynamics simulations were carried out on systems representing
      the gas and the bulk phase of 1-ethyl-3-methylimidazolium ethylsulfate
      [C(2)C(1)im][C(2)SO(4)]. The power spectra and cation-anion spatial distribution
      revealed different interactions of the anion and cation in the bulk phase versus
      the gas phase. In the bulk phase, all oxygen atoms of the anions are involved and
      interaction via the rear hydrogen atoms is possible, forming a closer packed
      system. The alkyl groups of cations and anions governed by dispersion interaction
      stick together in the bulk but are relatively free in the gas phase.

PMID- 22859057
TI  - Microfluidic designs and techniques using lab-on-a-chip devices for pathogen
      detection for point-of-care diagnostics.
AB  - Effective pathogen detection is an essential prerequisite for the prevention and
      treatment of infectious diseases. Despite recent advances in biosensors,
      infectious diseases remain a major cause of illnesses and mortality throughout
      the world. For instance in developing countries, infectious diseases account for
      over half of the mortality rate. Pathogen detection platforms provide a
      fundamental tool in different fields including clinical diagnostics, pathology,
      drug discovery, clinical research, disease outbreaks, and food safety.
      Microfluidic lab-on-a-chip (LOC) devices offer many advantages for pathogen
      detection such as miniaturization, small sample volume, portability, rapid
      detection time and point-of-care diagnosis. This review paper outlines recent
      microfluidic based devices and LOC design strategies for pathogen detection with
      the main focus on the integration of different techniques that led to the
      development of sample-to-result devices. Several examples of recently developed
      devices are presented along with respective advantages and limitations of each
      design. Progresses made in biomarkers, sample preparation, amplification and
      fluid handling techniques using microfluidic platforms are also covered and
      strategies for multiplexing and high-throughput analysis, as well as point-of
      care diagnosis, are discussed.

PMID- 22859058
TI  - Three years later: an assessment of the implementation of the Family Smoking
      Prevention and Tobacco Control Act.

PMID- 22859059
TI  - Altered tissue electrical properties in squamous cell carcinoma in head and neck
      tumors: Preliminary observations.
AB  - BACKGROUND: The purpose of this study was to investigate tissue electrical
      properties in patients with head and neck cancer. METHODS: In the cross-sectional
      study direct bioimpedance measures (resistance, reactance, and phase angle)
      determined by bioelectrical impedance analysis (BIA) were performed on 31
      patients with head and neck cancer and 31 healthy volunteers matched by age and
      sex as a control group. RESULTS: Phase angle at 50 kHz was found to be
      significantly lower (p = .000006) in patients with head and neck cancer than in
      the control group (4.69 degrees  +/- 0.71 vs 5.59 degrees  +/- 0.70,
      respectively). Resistance was significantly (p = .0002) greater in patients with
      head and neck cancer than in the control group (596.24 +/- 96.31 ohm vs 513.73 +/
      65.79 ohm, respectively). CONCLUSION: Presurgical patients diagnosed with head
      and neck cancer have altered tissue electrical properties. Further observations
      would be valuable to calculate survival, validate the prognostic significance of
      phase angle, and monitor nutritional and therapeutic interventions in this
      patient population.

PMID- 22859060
TI  - Disordered purinergic signaling and abnormal cellular metabolism are associated
      with development of liver cancer in Cd39/ENTPD1 null mice.
AB  - Liver cancer is associated with chronic inflammation, which is linked to immune
      dysregulation, disordered metabolism, and aberrant cell proliferation. Nucleoside
      triphosphate diphosphohydrolase-1; (CD39/ENTPD1) is an ectonucleotidase that
      regulates extracellular nucleotide/nucleoside concentrations by scavenging
      nucleotides to ultimately generate adenosine. These properties inhibit antitumor
      immune responses and promote angiogenesis, being permissive for the growth of
      transplanted tumors. Here we show that Cd39 deletion promotes development of both
      induced and spontaneous autochthonous liver cancer in mice. Loss of Cd39 results
      in higher concentrations of extracellular nucleotides, which stimulate
      proliferation of hepatocytes, abrogate autophagy, and disrupt glycolytic
      metabolism. Constitutive activation of Ras-mitogen-activated protein kinase
      (MAPK) and mammalian target of rapamycin (mTOR)-S6K1 pathways occurs in both
      quiescent Cd39 null hepatocytes in vitro and liver tissues in vivo. Exogenous
      adenosine 5'-triphosphate (ATP) boosts these signaling pathways, whereas
      rapamycin inhibits such aberrant responses in hepatocytes. CONCLUSION: Deletion
      of Cd39 and resulting changes in disordered purinergic signaling perturb
      hepatocellular metabolic/proliferative responses, paradoxically resulting in
      malignant transformation. These findings might impact adjunctive therapies for
      cancer. Our studies indicate that the biology of autochthonous and transplanted
      tumors is quite distinct.

PMID- 22859061
TI  - Studies on photodegradation of levomepromazine and olanzapine under simulated
      environmental conditions.
AB  - The present study discusses the influence of sunlight on the photostability of
      levomepromazine (LV) and olanzapine (OLA) hydrochlorides in river water. Four
      samples of water from different rivers were used in the research. In their
      course, it turned out that levomepromazine easily underwent photooxidation under
      simulated environmental conditions, resulting in the generation of its
      sulphoxide. Olanzapine, on the other hand, appeared to be more resistant to
      sunlight, as its photodecomposition proceeded slowly, and only one product of its
      decomposition was detected spectrophotometrically during the process. The
      photodegradation was analyzed in detail using principal component analysis (PCA)
      and multivariate curve resolution alternating least squares (MCR-ALS) chemometric
      methods, and the outcomes verified by HPLC and GC-MS analysis. It can be stated
      that the rates of the observed processes heavily depended on the chemical
      composition of the fresh water used in the experiments.

PMID- 22859062
TI  - Anti-neoplastic effects of fucoxanthin and its deacetylated product,
      fucoxanthinol, on Burkitt's and Hodgkin's lymphoma cells.
AB  - Fucoxanthin (FX) is a natural carotenoid with reported antitumorigenic activity.
      This study explored the effects of FX and its deacetylated product, fucoxanthinol
      (FXOH), on B-cell malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma
      and Epstein-Barr virus-immortalized B cells. Both FX and FXOH reduced the
      viability of these malignant B cells in a dose-dependent manner accompanied by
      the induction of cell cycle arrest during G1 phase and caspase-dependent
      apoptosis. FXOH was approximately twice more potent than FX in these activities.
      In contrast, normal peripheral blood mononuclear cells were resistant to FX and
      FXOH. Strong and constitutive activation of nuclear factor-kappaB (NF-kappaB) is
      a common characteristic of many B-cell malignancies, and FXOH suppressed
      constitutive NF-kappaB activity. NF-kappaB inhibition was accompanied by
      downregulation of NF-kappaB-dependent anti-apoptotic and cell cycle regulator
      gene products, including Bcl-2, cIAP-2, XIAP, cyclin D1 and cyclin D2. The
      results indicated that FX and FXOH are potentially useful therapeutic agents in B
      cell malignancies characterized by aberrant regulation of NF-kappaB.

PMID- 22859063
TI  - Long-term functioning and sleep quality in patients with major depressive
      disorder treated with extended-release quetiapine fumarate.
AB  - The aim of this study was to assess patients' functioning and sleep quality
      during extended-release quetiapine fumarate (quetiapine XR) maintenance
      treatment. A double-blind, randomized-withdrawal maintenance study of quetiapine
      XR monotherapy was carried out in patients with major depressive disorder.
      Following 4-8 weeks of open-label quetiapine XR and 12-18 weeks of open-label
      quetiapine XR stabilization (50, 150, or 300 mg/day), eligible patients were
      randomized to quetiapine XR (50, 150, or 300 mg/day) or placebo. Secondary
      variables of the Sheehan Disability Scale (SDS) and the Pittsburgh Sleep Quality
      Index (PSQI) were used to assess functioning and sleep quality and are reported
      here. Quetiapine XR significantly maintained functioning versus placebo. Changes
      in the least squares means (LSM) from randomization in the SDS total scores were
      as follows: -0.45, quetiapine XR (P<0.05), versus 0.44, placebo. Quetiapine XR
      significantly maintained SDS domains 'social life/leisure' (-0.19; P<0.05) and
      'family life/home responsibilities' (-0.22; P<0.05) versus placebo (0.13 and
      0.10, respectively). Quetiapine XR significantly maintained sleep quality (LSM
      change in PSQI total scores: 0.06, quetiapine XR vs. 1.35, placebo; P<0.001),
      with five of seven PSQI components being significant for quetiapine XR versus
      placebo. In conclusion, quetiapine XR (50-300 mg/day) monotherapy better
      maintains overall functioning and sleep quality than placebo in patients with
      major depressive disorder.

PMID- 22859064
TI  - Quetiapine augmentation of serotonin reuptake inhibitors in treatment-refractory
      obsessive-compulsive disorder:  is response to treatment predictable?
AB  - Several studies have examined the predictors of treatment response in obsessive
      compulsive disorder (OCD). Only limited information is available on the
      predictors of response to antipsychotic augmentation of serotonin reuptake
      inhibitors (SRIs). Data from placebo-controlled studies of augmentation with
      quetiapine were combined in a best subsets logistic regression to derive a
      predictive model for Yale-Brown obsessive-compulsive scale (YBOCS) change and the
      YBOCS endpoint. Data from the YBOCS checklist and a variety of clinical and
      demographic variables previously shown to predict treatment outcome in OCD were
      analysed. In univariate analyses, the failure of fewer previous SRI trials was
      associated with the YBOCS response. In the multivariate model, for YBOCS change,
      45% of the variance was attributed to the fact that patients had failed fewer
      previous SRI treatments, had higher baseline obsession scores, and ordering and
      arranging compulsions. For the YBOCS endpoint scores, 50% of the variance was
      attributed to the fact that patients had fewer failed SRI trials, higher baseline
      compulsion scores, and counting/ordering and arranging compulsions. These data
      indicate a number of predictors of response to augmentation of SRIs in treatment
      refractory OCD. These include fewer previously failed SRI trials and generally
      higher overall baseline scores for obsessions and compulsions as well as
      counting/ordering and arranging compulsions. Other factors are, however, also
      likely to play an important role in predicting outcome.

PMID- 22859065
TI  - Rethinking the role of long-acting atypical antipsychotics in the community
      setting.
AB  - Schizophrenia is a relapsing and evolving condition, which requires treatment
      continuity. Increasing evidence shows that antipsychotic discontinuation is
      associated with relapse in most patients, and that early interventions have a
      positive impact on long-term outcomes. Poor adherence to antipsychotics is a
      major factor in the treatment of schizophrenia and a relevant risk factor for
      relapse. Considerable effort has been made toward improving adherence, including
      the development of long-acting injectable (LAI) antipsychotics. LAIs have
      traditionally been reserved for patients with repeated nonadherence; currently,
      several misconceptions prevent their more widespread use. The recent introduction
      of LAI formulations of atypical antipsychotics and the encouraging results in
      terms of the reduction in relapse rates and avoidance of hospitalization warrant
      a reassessment of the role of LAIs in the management of schizophrenia. This paper
      presents the position of a panel of nine Italian schizophrenia experts on the use
      of novel LAI medications, with a focus on community-based services, the
      prevailing setting of schizophrenia treatment in Italy. The need to change the
      attitude toward LAIs--no longer a treatment of last resort, but a component of
      multimodal strategies leading patients to remission and rehabilitation--is
      emphasized. The paper also presents recommendations for LAI atypical
      antipsychotic use in the community setting.

PMID- 22859066
TI  - Androgen-modulated p21 and p53 gene expression in human non-transformed
      epithelial prostatic cells in primary cultures.
AB  - The prostate gland is under androgen control. The aim of the present study was to
      evaluate the expression of two genes that are regulators of the cell cycle, the
      p53 and p21 genes, in human non-transformed epithelial prostatic cells (HNTEPs)
      treated with different concentrations of hormones. Samples of prostate tissue
      were obtained from 10 patients between 60 and 77 years of age. HNTEP cells were
      grown in basal medium and treated with dihydrotestosterone (DHT) in different
      conditions for 4 h. A low concentration of DHT resulted in a significant increase
      in cell growth; this effect was eradicated by addition of the antiandrogen
      hydroxyflutamide. Furthermore, the low concentration of DHT induced lower mRNA
      levels in the p53 and p21 genes in HNTEP cells. In turn, high DHT concentrations
      induced a significant increase in the expression of the p53 and p21 genes. The
      present data suggest that the p53 and p21 genes play a role in the control of
      responsiveness and androgen dose-dependent cell proliferation in HNTEP cells.
      Further studies are required to assess the intracellular signaling pathway
      regulated by p53 and p21 under the influence of androgens and its implications
      for the pathophysiology of prostate diseases.

PMID- 22859067
TI  - Network formation and photoluminescence in copper(I) halide complexes with
      substituted piperazine ligands.
AB  - The synthesis, X-ray structures and photophysics of ten complexes of CuX (X = I
      or Br) with bridging N-substituted and N,N'-disubstituted piperazines (Pip) are
      presented. Depending on the steric demand of the Pip substituents, the complexes
      fall into four categories: (CuX)(4)(Pip)(2), which are networks of linked
      Cu(4)X(4) cubane units, (CuX)(2)(Pip), which are chains of linked Cu(2)X(2)
      rhombs, and (CuX)(2)(Pip)(2) or (CuX)(4)(Pip)(4), which are simple rhomboid
      dimers and cubane tetramers. A combination of spectroscopic studies and DFT
      calculations was used to investigate the luminescence of the products. The
      results suggest that the relatively high energy emission seen in dimers is due to
      cluster-centred (XMLT/metal-centred) excitations for the aliphatic amines and
      MLCT (d ->pi*) for aromatic amines, and low energy emission seen in the tetramers
      is the result of cluster-centred transitions. The (CuI)(2)(Pip) complexes act as
      sensor materials, undergoing irreversible reaction with aliphatic and aromatic
      amines (Nu) in the vapour state, irreversibly producing cubanes (CuI)(4)Nu(4),
      with corresponding production of long wavelength emission.

PMID- 22859068
TI  - Measures of chirality and angular momentum in the electromagnetic field.
AB  - It is shown that prominent measures of the helicity of chiral electromagnetic
      radiation have a common basis, in differences between the populations of optical
      modes associated with angular momenta of opposite sign. The analysis helps to
      develop the interpretation of chiroptical phenomena in which such metrics have
      been treated as representing physically distinct "superchiral" phenomena.
      Constructing theory with due cognizance of photonic character, it emerges only
      that the spin angular momentum of light is engaged in such observations. In
      consequence, the term "superchiral" is redundant.

PMID- 22859069
TI  - Optical backpropagation for fiber-optic communications using optical phase
      conjugation at the receiver.
AB  - A fiber-optic system design with optical backpropagation that uses an optical
      phase conjugator, high-dispersion fibers, and highly nonlinear fibers is
      investigated. The proposed technique outperforms the midpoint optical phase
      conjugation and digital backpropagation with the same step size.

PMID- 22859070
TI  - Spatial modulation microscopy for real-time imaging of plasmonic nanoparticles
      and cells.
AB  - Spatial modulation microscopy (SMM) is a technique originally developed for
      quantitative spectroscopy of individual nano-objects. Here, a parallel
      implementation of the SMM technique is demonstrated based on a line detector
      capable of demodulation at kHz frequencies. The capabilities of the imaging
      system are shown using an array of plasmonic nanoantennas and dendritic cells
      incubated with gold nanoparticles.

PMID- 22859071
TI  - Offline estimation of decay time for an optical cavity with a low pass filter
      cavity model.
AB  - This Letter presents offline estimation results for the decay-time constant for
      an experimental Fabry-Perot optical cavity for cavity ring-down spectroscopy
      (CRDS). The cavity dynamics are modeled in terms of a low pass filter (LPF) with
      unity DC gain. This model is used by an extended Kalman filter (EKF) along with
      the recorded light intensity at the output of the cavity in order to estimate the
      decay-time constant. The estimation results using the LPF cavity model are
      compared to those obtained using the quadrature model for the cavity presented in
      previous work by Kallapur et al. The estimation process derived using the LPF
      model comprises two states as opposed to three states in the quadrature model.
      When considering the EKF, this means propagating two states and a (2*2)
      covariance matrix using the LPF model, as opposed to propagating three states and
      a (3*3) covariance matrix using the quadrature model. This gives the former model
      a computational advantage over the latter and leads to faster execution times for
      the corresponding EKF. It is shown in this Letter that the LPF model for the
      cavity with two filter states is computationally more efficient, converges
      faster, and is hence a more suitable method than the three-state quadrature model
      presented in previous work for real-time estimation of the decay-time constant
      for the cavity.

PMID- 22859072
TI  - Harmonic mode locking with reduced carrier-envelope phase noise in ytterbium
      doped fiber laser.
AB  - We experimentally explored the influence of passive harmonic mode locking on the
      temporal and spectral features of a ytterbium-doped fiber laser. Similar
      dependences of free-running linewidth of the laser carrier-envelope offset
      frequency (f0) on the intracavity net dispersion were observed for the
      fundamental-, second-, and third-order mode-locking states. Due to the reduction
      of nonlinear effects and supermode phase locking that balanced the third-order
      dispersion in the fiber cavity, the third-order harmonic mode-locking exhibited
      the narrowest free-running f0 linewidth of ~120 kHz in the near-zero net
      dispersion regime.

PMID- 22859073
TI  - Self-similar amplification in fiber Bragg gratings written in fiber amplifiers.
AB  - We show, by using numerical simulations, that self-similar pulses with a duration
      on the order of few nanoseconds and an energy on the order of 10 MUJ can be
      obtained at the output of a fiber Bragg grating (FBG) written in a fiber
      amplifier. The evolution of the amplified pulses is determined by the combined
      effect of Kerr nonlinearity, normal-dispersion, gain, and gain saturation, which
      limit the pulse energy. The output pulse mainly depends on the initial pulse
      energy rather than on the initial pulse profile. The reduced group velocity in
      FBGs can significantly increase the total gain for a given amplifier length.
      Hence we find that the proposed amplification scheme can be highly advantageous
      for amplification of nanosecond-scale pulses in fiber amplifiers.

PMID- 22859074
TI  - Phase-locked pulses for two-dimensional spectroscopy by a birefringent delay
      line.
AB  - We introduce the translating wedge-based identical pulses encoding system, a
      novel device for the generation of collinear, interferometrically locked
      ultrashort pulse pairs. By means of birefringent wedges, we are able to control
      the pulse delay with attosecond precision and stability better that lambda/360,
      without affecting the pulse duration and in a spectral range that spans from UV
      to mid-IR. This device is expected to dramatically simplify two-dimensional
      spectroscopy experiments.

PMID- 22859075
TI  - Three-dimensional photonic component for multichannel coherence measurements.
AB  - We present the experimental results of a three-dimensional integrated photonic
      component designed for the simultaneous determination of mutual coherence
      properties of three light channels. Potential applications to astronomical
      optical interferometry are proposed and discussed.

PMID- 22859076
TI  - Investigating the interaction of x-ray free electron laser radiation with grating
      structure.
AB  - The interaction of free electron laser pulses with grating structure is
      investigated using 4.6+/-0.1 nm radiation at the FLASH facility in Hamburg. For
      fluences above 63.7+/-8.7 mJ/cm2, the interaction triggers a damage process
      starting at the edge of the grating structure as evidenced by optical and atomic
      force microscopy. Simulations based on solution of the Helmholtz equation
      demonstrate an enhancement of the electric field intensity distribution at the
      edge of the grating structure. A procedure is finally deduced to evaluate damage
      threshold.

PMID- 22859077
TI  - Surface induced anisotropy of metal-dielectric composites and the anomalous spin
      Hall effect.
AB  - We show that optical anisotropy can exist in composite materials even when they
      consist of components that are isotropic in shape, spatial distribution, and
      optical properties. We demonstrate that the simple presence of a surface on a
      metal-dielectric composite induces an optical anisotropy that manifests itself in
      an unusual change of the state of polarization and spin Hall effect of reflected
      light.

PMID- 22859078
TI  - Gallium-nitride-based plasmonic multilayer operating at 1.55 MUm.
AB  - In this Letter, we have designed and fabricated a III-V semiconductor multilayer
      based on surface plasmon resonance (SPR) operating at the telecom wavelength.
      Optimization of the optogeometrical parameters and the metal/semiconductor layers
      required for this novel structure was conducted accurately by theoretical tools
      using the Maxwell equations. Technological fabrication of the device and its
      experimental characterizations using an evanescent coupling configuration was
      performed: the results have confirmed the existence of SPR associated to a sharp
      width response. This study could be a first step in the design of new plasmonic
      semiconductor-based optical devices such as modulators and switches.

PMID- 22859079
TI  - Doping management for high-power fiber lasers: 100 W, few-picosecond pulse
      generation from an all-fiber-integrated amplifier.
AB  - Thermal effects, which limit the average power, can be minimized by using low
      doped, longer gain fibers, whereas the presence of nonlinear effects requires use
      of high-doped, shorter fibers to maximize the peak power. We propose the use of
      varying doping levels along the gain fiber to circumvent these opposing
      requirements. By analogy to dispersion management and nonlinearity management, we
      refer to this scheme as doping management. As a practical first implementation,
      we report on the development of a fiber laser-amplifier system, the last stage of
      which has a hybrid gain fiber composed of high-doped and low-doped Yb fibers. The
      amplifier generates 100 W at 100 MHz with pulse energy of 1 MUJ. The seed source
      is a passively mode-locked fiber oscillator operating in the all-normal
      dispersion regime. The amplifier comprises three stages, which are all-fiber
      integrated, delivering 13 ps pulses at full power. By optionally placing a
      grating compressor after the first stage amplifier, chirp of the seed pulses can
      be controlled, which allows an extra degree of freedom in the interplay between
      dispersion and self-phase modulation. This way, the laser delivers 4.5 ps pulses
      with ~200 kW peak power directly from fiber, without using external pulse
      compression.

PMID- 22859080
TI  - Enhanced performance of thin-disk lasers by pumping into the zero-phonon line.
AB  - Pumping Yb:YAG or Yb:LuAG into the zero-phonon line at 969 nm instead of using
      the common pump wavelength of 940 nm reduces the heat generation by 32%. In
      addition to the 3% increase of the Stokes efficiency, this significantly reduces
      the diffraction losses caused by the thermally induced phase distortions leading
      to a remarkable increase of the overall efficiency especially of fundamental-mode
      thin-disk lasers. Using this pumping scheme in an Yb:LuAG thin-disk laser, we
      achieved 742 W of nearly diffraction limited (M2~1.5) output power at an
      unprecedented high optical efficiency of 58.5%. For multimode operation (M2~15)
      the maximum optical efficiency of an Yb:YAG thin-disk laser was increased to 72%.

PMID- 22859082
TI  - Photolytic-interference-free, femtosecond two-photon fluorescence imaging of
      atomic hydrogen.
AB  - We discuss photolytic-interference-free, high-repetition-rate imaging of reaction
      intermediates in flames and plasmas using femtosecond (fs) multiphoton
      excitation. The high peak power of fs pulses enables efficient nonlinear
      excitation, while the low energy nearly eliminates interfering single-photon
      photodissociation processes. We demonstrate proof-of-principle, interference
      free, two-photon laser-induced fluorescence line imaging of atomic hydrogen in
      hydrocarbon flames and discuss the method's implications for certain other atomic
      and molecular species.

PMID- 22859081
TI  - Structured interference optical coherence tomography.
AB  - We developed a structured interference optical coherence tomography (SIOCT) to
      enhance the lateral resolution beyond the diffraction limit. A sinusoidal pattern
      is created on the interferometric beam with the reference intensity temporally
      modulated. In the Fourier domain, the high spatial frequencies are shifted into
      the detectable range, which enhances the lateral resolution beyond the
      diffraction limit by a factor of 2. The lateral resolution of SIOCT was
      characterized in our study as ~5.5 MUm, surpassing the diffraction limit ~9.6 MUm
      as in conventional Fourier-domain optical coherence tomography. SIOCT was
      demonstrated on phantoms and ex vivo adipose tissues.

PMID- 22859083
TI  - Propagation and modulation of Airy beams through a four-level electromagnetic
      induced transparency atomic vapor.
AB  - We study the propagation properties of an Airy beam through a four-level
      electromagnetic induced transparency (EIT) atomic vapor. The analytical
      expression for the Airy beam passing through the ABCD optical system of the EIT
      vapor is deduced and employed to analyze the propagation characteristics of the
      beam. It is shown that both the deflection position and the intensity of the Airy
      beam can be modulated by the Rabi frequency of the control light. Such a tunable
      optical behavior may have some potential applications in medicine science.

PMID- 22859084
TI  - Core-pumped gain-guided index-antiguided continuous wave lasing in dispersion
      engineered erbium-doped fiber.
AB  - We demonstrate core-pumped gain-guided index-antiguided fiber lasers using a 22
      cm long dispersion-engineered erbium-doped fiber. The erbium-doped fiber is
      dispersion-engineered using optical liquid to replace the most part of silica
      cladding so that the index of core turns out to be higher (lower) than that of
      new cladding at pump (lasing) wavelength, respectively. The pump light is
      confined to propagate in core based on an index-guiding mechanism to efficiently
      excite the gain medium running through the fiber whereas the cw lasing is
      constructed in a long, small-core waveguide under a gain-guided, index-antiguided
      situation.

PMID- 22859085
TI  - 64*64 pixel smart sensor array for laser Doppler blood flow imaging.
AB  - What is believed to be the first fully integrated two-dimensional complementary
      metal oxide semiconductor (CMOS) imaging array for laser Doppler blood flow
      imaging is demonstrated. The sensor has 64*64 pixels and includes both analog and
      digital on-chip processing electronics. This offers several potential advantages
      over commercial sensors as the processing is tailored to the signals of interest
      and the data bottleneck that exists between the sensor and processing electronics
      is overcome. To obtain a space efficient design over 64*64 pixels means that
      standard processing electronics used off-chip cannot be implemented. Images of
      both simulated blood flow responses and a blood flow occlusion test demonstrate
      the capability.

PMID- 22859086
TI  - Simultaneous measurement of partial pressure of O2 and CO2 with a hybrid
      interferometer.
AB  - In this Letter, a hybrid interferometer for simultaneous measurement of the
      partial pressures of O2 and CO2 mixtures is reported. The sensing head consists
      in the combination of two interferometric structures, one a Fabry-Perrot cavity
      and the other a modal interferometer. The intrinsic Fabry-Perot was formed by
      splicing a single mode fiber with a graded index fiber length that was then
      subjected to chemical etching creating an air cavity. The second interferometer
      is based on a splice of a pure silica tube in series with the Fabry-Perot. It was
      observed for a particular gas that its refractive index changes with pressure
      variation in a specific way, a characteristic that permitted the simultaneous
      measurement of partial pressures of CO2 and O2 with rms deviations of ~+/-48.7
      kPa and ~+/-20.1 kPa, respectively.

PMID- 22859087
TI  - Bandwidth scaling and spectral flatness enhancement of optical frequency combs
      from phase-modulated continuous-wave lasers using cascaded four-wave mixing.
AB  - We introduce a new cascaded four-wave mixing technique that scales up the
      bandwidth of frequency combs generated by phase modulation of a continuous-wave
      (CW) laser while simultaneously enhancing the spectral flatness. As a result, we
      demonstrate a 10 GHz frequency comb with over 100 lines in a 10 dB bandwidth in
      which a record 75 lines are within a flatness of 1 dB. The cascaded four-wave
      mixing process increases the bandwidth of the initial comb generated by the
      modulation of a CW laser by a factor of five. The broadband comb has
      approximately quadratic spectral phase, which is compensated upon propagation in
      single-mode fiber, resulting in a 10 GHz train of 940 fs pulses.

PMID- 22859088
TI  - Polarization-resolved imaging of an ensemble of waveguide modes.
AB  - We demonstrate polarization-sensitive measurement of the modal content of
      waveguides by generalizing the classic rotating wave-plate-based polarimeter to
      wide-field optical low-coherence interferometry. The spatial phases of the modes
      are retrieved with principal component analysis. By applying this polarization
      sensitive cross-correlation (C2) imaging technique to the characterization of a
      few-mode fiber, we reveal that different modes experience distinct bend-induced
      birefringence in optical fibers. This polarization-resolved C2 imaging is well
      suited for analyzing the impact of polarization on wave propagation in high-power
      fiber lasers as well as in mode-division-multiplexed communications systems.

PMID- 22859089
TI  - Narrowband ultraviolet photodetector based on MgZnO and NPB heterojunction.
AB  - An ultraviolet photodetector was fabricated based on Mg0.07Zn0.93O
      heterojunction. N, N'-bis (naphthalen-1-y1)-N, N'-bis(pheny) benzidine was
      selected as the hole transporting layer. I-V characteristic curves of the device
      were measured in the dark and under the illumination of 340 nm UV light with
      density of 1.33 mW/cm2. The device showed a low dark current of about 3*10(-10) A
      and a high photo-dark current ratio of 1*10(5) at -2 V bias. A narrowband
      photoresponse was observed from 300 to 400 nm and centered at 340 nm with a full
      width at half-maximum of only 30 nm. The maximum peak response is at 340 nm,
      which is 0.192 A/W at the bias of -1 V.

PMID- 22859090
TI  - Compressed sensing with linear-in-wavenumber sampling in spectral-domain optical
      coherence tomography.
AB  - We propose a novel method called compressed sensing with linear-in-wavenumber
      sampling (k-linear CS) to retrieve an image for spectral-domain optical coherence
      tomography (SD-OCT). An array of points that is evenly spaced in wavenumber
      domain is sampled from an original interferogram by a preset k-linear mask. Then
      the compressed sensing based on l1 norm minimization is applied on these points
      to reconstruct an A-scan data. To get an OCT image, this method uses less than
      20% of the total data as required in the typical process and gets rid of the
      spectral calibration with numerical interpolation in traditional CS-OCT.
      Therefore k-linear CS is favorable for high speed imaging. It is demonstrated
      that the k-linear CS has the same axial resolution performance with ~30 dB higher
      signal-to-noise ratio (SNR) as compared with the numerical interpolation. Imaging
      of bio-tissue by SD-OCT with k-linear CS is also demonstrated.

PMID- 22859091
TI  - Determination of complex modes in photonic crystal waveguides using the phase
      variation in characteristic coefficients.
AB  - An efficient frequency-domain method, the phase variation monitoring (PVM)
      method, is proposed to determine the electromagnetic eigenmodes in two
      dimensional photonic crystal waveguides. The proposed method is based on
      monitoring the reflection and transmission coefficients of incident plane waves.
      It is successfully applied to an illustrative line-defect photonic crystal
      waveguide and proved to be capable of calculating the in-plane leakage through
      the finite-size photonic crystal surrounding the line-defect. Calculation of the
      leakage loss is not only important for proper understanding of wave propagation
      within the defect but also for its significant role in applications of photonic
      structures.

PMID- 22859092
TI  - Visual device for pressure measurement using photonic crystal slabs.
AB  - We propose and demonstrate a visual, all-optical pressure-measuring device
      composed of a flexible membrane dilating toward a photonic crystal slab. Due to
      its transparency and capability to be miniaturized, it may be integrated on the
      inner side of an artificial lens and directly measure the eye's intraocular
      pressure. Using crossed polarization filters for the readout process, we obtain a
      contrast enhancement for the circular contact area of the membrane with the
      photonic crystal slab. We demonstrate that the visible circle increases as a
      function of pressure.

PMID- 22859093
TI  - Frequency comb stabilization with bandwidth beyond the limit of gain lifetime by
      an intracavity graphene electro-optic modulator.
AB  - Intracavity loss modulation enables offset-frequency control with bandwidths
      beyond what is possible by pump power modulation. To demonstrate this new method,
      we use a subwavelength thick graphene electro-optic modulator to stabilize the
      offset frequency in a Tm:fiber frequency comb at 1.95 MUm wavelength. Record-low
      residual phase noise of 144 mrads was achieved with this new locking scheme.

PMID- 22859094
TI  - Monocrystalline silicon photovoltaic luminescent solar concentrator with 4.2%
      power conversion efficiency.
AB  - We report conversion efficiencies of experimental single and dual light guide
      luminescent solar concentrators. We have built several 5 cm * 5 cm and 10* cm *
      10 cm luminescent solar concentrator (LSC) demonstrators consisting of c-Si
      photovoltaic cells attached to luminescent light guides of Lumogen F Red 305 dye
      and perylene perinone dye. The highest overall efficiency obtained was 4.2% on a
      5 cm * 5 cm stacked dual light guide using both luminescent materials. To our
      knowledge, this is the highest reported experimentally determined efficiency for
      c-Si photovoltaic-based LSCs. Furthermore, we also produced a 5 cm * 5 cm LSC
      specimen based on an inorganic phosphor layer with an overall efficiency of 2.5%.

PMID- 22859095
TI  - Conjugate Fabry-Perot cavity pair for improved astro-comb accuracy.
AB  - We propose a new astro-comb mode-filtering scheme composed of two Fabry-Perot
      cavities (coined "conjugate Fabry-Perot cavity pair"). Simulations indicate that
      this new filtering scheme makes the accuracy of astro-comb spectral lines more
      robust against systematic errors induced by nonlinear processes associated with
      power-amplifying and spectral-broadening optical fibers.

PMID- 22859096
TI  - Deep-subwavelength waveguiding via inhomogeneous second-harmonic generation.
AB  - We theoretically investigate second-harmonic generation in extremely narrow,
      subwavelength semiconductor and dielectric waveguides. We discuss a guiding
      mechanism characterized by the inhibition of diffraction and the suppression of
      cutoff limits in the context of a light trapping phenomenon that sets in under
      conditions of general phase and group velocity mismatch between the fundamental
      and the generated harmonic.

PMID- 22859097
TI  - Integrated optical devices based on broadband epsilon-near-zero meta-atoms.
AB  - We verify the feasibility of the proposed theoretical strategy for designing the
      broadband near-zero permittivity (ENZ) metamaterial at optical frequency range
      with numerical simulations. In addition, the designed broadband ENZ stack is used
      as meta-atoms to build functional nanophotonic devices with extraordinary
      properties, including an ultranarrow electromagnetic energy tunneling channel and
      an ENZ concave focusing lens.

PMID- 22859098
TI  - All-fiber integrated 10 GHz repetition rate femtosecond laser source based on
      Raman compression of pulses generated through spectral masking of a phase
      modulated diode.
AB  - We report the development of a 10 GHz repetition rate all-fiber integrated
      femtosecond source tunable around 1.55 MUm. A phase modulator and sharp spectral
      filter are used to convert the output of a tunable CW diode to a 10 GHz pulse
      train. These pulses are compressed using Raman soliton adiabatic compression in a
      21 km long length of fiber to generate sub-300-fs duration pulses at a 10 GHz
      repetition rate. By tuning the wavelength of the diode and appropriate filtering,
      similar performance was achieved over a 20 nm bandwidth.

PMID- 22859099
TI  - Instantaneous quadrature components or Jones vector retrieval using the
      Pancharatnam-Berry phase in frequency domain low-coherence interferometry.
AB  - We use the Pancharatnam-Berry phase as a multifunctional tool for low-coherence
      interferometry. This geometric phase shift enables instantaneous retrieval of the
      quadrature components of the complex interferometric signal. The phase shift is
      independent of wavelength and allows for a complex conjugate suppression of 40 dB
      for an optical bandwidth of 115 nm. Furthermore, this paper investigates the
      versatility of the geometric phase to perform polarization sensitive
      measurements. The Jones vector of the sample was obtained numerically, allowing
      sample birefringence and optical axis calculation.

PMID- 22859100
TI  - Full range spectral domain optical coherence tomography using a fiber-optic probe
      as a self-phase shifter.
AB  - We present a full range handheld probe type spectral domain optical coherence
      tomography (SD-OCT) method. Here, the sample arm is composed of a tilted fiber
      optic cantilever scanner; thus, the phase shift concurrently occurs while sample
      scanning. With the phase shift, we could achieve a full range complex-conjugate
      free OCT image with no additional phase shifters in the reference arm. To realize
      this technique, a magnetically actuated probe was adopted. Full range SD-OCT
      images of a pearl, human fingernail, and human tooth were subsequently obtained
      using this suggested probe. The scanning range and acquisition speed were 3 mm
      and 20 frames/s, respectively.

PMID- 22859101
TI  - Effect of hole-shape irregularities on photonic crystal waveguides.
AB  - The effect of irregular hole shape on the spectrum and radiation losses of a
      photonic crystal waveguide is studied using Bloch-mode expansion. Deviations from
      a circular hole are characterized by a radius fluctuation amplitude and
      correlation angle. It is found that the parameter that determines the magnitude
      of the effect of disorder is the standard deviation of the hole areas. Hence, for
      a fixed amplitude of the radius fluctuation around the hole, those effects are
      strongly dependent on the correlation angle of the irregular shape, which
      suggests how to potentially improve the quality of photonic crystal structures.

PMID- 22859102
TI  - Design and fabrication of hollow-core photonic crystal fibers for high-power
      ultrashort pulse transportation and pulse compression.
AB  - We report on the recent design and fabrication of kagome-type hollow-core
      photonic crystal fibers for the purpose of high-power ultrashort pulse
      transportation. The fabricated seven-cell three-ring hypocycloid-shaped large
      core fiber exhibits an up-to-date lowest attenuation (among all kagome fibers) of
      40 dB/km over a broadband transmission centered at 1500 nm. We show that the
      large core size, low attenuation, broadband transmission, single-mode guidance,
      and low dispersion make it an ideal host for high-power laser beam
      transportation. By filling the fiber with helium gas, a 74 MUJ, 850 fs, and 40
      kHz repetition rate ultrashort pulse at 1550 nm has been faithfully delivered at
      the fiber output with little propagation pulse distortion. Compression of a 105
      MUJ laser pulse from 850 fs down to 300 fs has been achieved by operating the
      fiber in ambient air.

PMID- 22859103
TI  - Trimming of high-Q-factor silicon ring resonators by electron beam bleaching.
AB  - We demonstrate a novel position-resolved resonance trimming strategy for silicon
      ring resonators. Ring resonators are covered with a chromophore-doped guest host
      polymer cladding. Illumination of the polymer cladding with high-energy electrons
      causes a bleaching of the chromophore molecules. Bleaching of the chromophores
      induces a reduction of the polymer refractive index, which can be used to trim
      the resonance frequency of the ring resonators. A maximum refractive index change
      of 0.06 and a TM polarization resonance shift of 16.4 nm have been measured. A Q
      factor of 20,000 before bleaching remains unaltered after the electron beam
      exposure process.

PMID- 22859104
TI  - External-cavity diode laser in second-order Littrow configuration.
AB  - In this Letter, we propose and demonstrate an external-cavity diode laser in
      second-order Littrow configuration. This topology utilizes a low-efficiency
      diffraction grating to establish a high-finesse external cavity, strong optical
      feedback, a high polarization discrimination, and a circular TEM00 output mode.
      In our proof-of-concept experiment, we realized a cavity with a finesse of 1855,
      being, to the best of our knowledge, the highest value ever reported for a three
      port-grating-coupled cavity. With optical feedback, the laser threshold of the
      laser diode employed was reduced by a factor of 4.

PMID- 22859105
TI  - Visible reconstruction by a circular holographic display from digital holograms
      recorded under infrared illumination.
AB  - A circular holographic display that consists of phase-only spatial light
      modulators is used to reconstruct images in visible light from digital holograms
      recorded under infrared (10.6 MUm) illumination. The reconstruction yields a
      holographic digital video display of a three-dimensional ghostlike image of an
      object floating in space where observers can move and rotate around it.

PMID- 22859106
TI  - Perpendicular coupler for whispering-gallery resonators.
AB  - In this Letter, we report on a perpendicular coupler (PC) for whispering-gallery
      resonators; it is a near field waveguide optimized for high coupling efficiency.
      The PC provides highly efficient tunneling coupling between the waveguide and
      microresonator without the need of a phase matching condition, and saves space
      for integration components. Compared to the Lorentz-shape in the transmission
      spectrum of the parallel coupler, the reflection spectrum of the PC shows an
      asymmetric Fano-shape near resonance. Furthermore, we demonstrate that the
      collection efficiency can be enhanced by near field scatterers, with a maximal
      efficiency of about 75%. Our simulations show that the PC is not sensitive to
      most parameters (including the refractive index of the waveguide), which makes
      the PC optimal for the application of whispering-gallery modes.

PMID- 22859107
TI  - Strategy for automatic and complete three-dimensional optical digitization.
AB  - This Letter proposes a new strategy of a three-dimensional (3D) scanning pipeline
      to achieve complete 3D digitization of complex objects in a real scene. This
      strategy consists of a one-dimensional array of optical 3D sensors combined with
      an automatically controlled turntable. An efficient calibration method for the
      sensor array is presented to guarantee the accuracy of the 3D measurement.
      Furthermore, an automatic registration technique is also proposed for aligning
      multiple range images taken from sensor array. Experiment results are also
      presented to demonstrate the proposed approach.

PMID- 22859108
TI  - Rayleigh scattering-assisted narrow linewidth Brillouin lasing in cascaded fiber.
AB  - We report a single frequency lasing phenomenon with a narrow linewidth of ~3 kHz
      in cascaded fiber that is composed of three types of low-loss communication
      fibers. The Rayleigh scattering of the Brillouin Stokes light created in the
      middle fiber section along both directions is enhanced by the other two fiber
      sections. When the Brillouin gain of the middle fiber exceeds the effective loss
      of the Brillouin stokes light in a roundtrip, a narrow linewidth lasing is
      observed on the top of the Brillouin spectrum line of the middle fiber. To the
      best of our knowledge, it is the first report on Rayleigh scattering-assisted
      Brillouin lasing with single frequency and narrow linewidth in cascaded low-loss
      communication fibers.

PMID- 22859109
TI  - Woofer-tweeter temporal correctors split in atmospheric adaptive optics.
AB  - Many adaptive optics applications require wavefront corrections with a high
      stroke, and at a high bandwidth. Often, these two requirements cannot be met by a
      single wavefront corrector, and, instead, the combination of a low-bandwidth,
      high-stroke woofer and a high-bandwidth low-stroke tweeter is used in a so-called
      woofer-tweeter architecture. The optimal (minimum residual phase variance) way to
      split the correction between the woofer and the tweeter in the context of a
      linear-quadratic-Gaussian (LQG) controller has been addressed previously.
      However, the necessity to fold the temporal characteristics of the woofer and
      tweeter into the LQG controller significantly increases its complexity. In this
      Letter, this optimal strategy is compared to a simpler, ad hoc approach, which
      consists in optimizing the LQG controller as if it were controlling a high
      bandwidth, high-stroke corrector and splitting the correction using first-order
      high- and low-pass temporal filters. In the case of tilt correction for NFIRAOS
      on the Thirty Meter Telescope, it is found that the ad hoc approach, which is
      already used or planned for several systems, holds the same overall correction
      performance compared to the optimal strategy.

PMID- 22859110
TI  - High-quality generation of a multispot pattern using a spatial light modulator
      with adaptive feedback.
AB  - We propose and demonstrate high-quality generation of a uniform multispot pattern
      (MSP) by using a spatial light modulator with adaptive feedback. The method
      iteratively updates a computer generated hologram (CGH) using correction
      coefficients to improve the intensity distribution of the generated MSP in the
      optical system. Thanks to a simple method of determining the correction
      coefficients, the computational cost for optimizing the CGH is low, while
      maintaining high uniformity of the generated MSP. We demonstrate the generation
      of a 28*28 square-aligned MSP with high uniformity. Additionally, the proposed
      method could generate an MSP with a gradually varying intensity profile, as well
      as a uniform MSP consisting of more than 1000 spots arranged in an arbitrary
      pattern.

PMID- 22859111
TI  - Stressed waveguides with tubular depressed-cladding inscribed in phosphate
      glasses by femtosecond hollow laser beams.
AB  - We report on the single-step fabrication of stressed optical waveguides with
      tubular depressed-refractive-index cladding in phosphate glasses by the use of
      focused femtosecond hollow laser beams. Tubelike low index regions appear under
      direct exposure due to material rarefaction following expansion. Strained
      compacted zones emerged in domains neighboring the tubular track of lower
      refractive index, and waveguiding occurs mainly within the tube core fabricated
      by the engineered femtosecond laser beam. The refractive index profile of the
      optical waveguide was reconstructed from the measured transmitted near-field
      intensity.

PMID- 22859112
TI  - Compact diode-laser-pumped quantum light source based on four-wave mixing in hot
      rubidium vapor.
AB  - Using a nondegenerate four-wave mixing process in hot rubidium vapor, we
      demonstrate a compact diode-laser-pumped system for the generation of intensity
      difference squeezing down to 8 kHz with a maximum squeezing of -7 dB. To the best
      of our knowledge, this is the first demonstration of kilohertz-level intensity
      difference squeezing using a semiconductor laser as the pump source. This scheme
      is of interest for experiments involving atomic ensembles, quantum
      communications, and precision measurements. The diode-laser-pumped system would
      extend the range of possible applications for squeezing due to its low cost, ease
      of operation, and ease of integration.

PMID- 22859113
TI  - Exploring spatial resolution in high-sensitivity nanogap quantum dot
      photodetectors.
AB  - We propose a new approach to experimentally determine the spatial resolution of
      nanogap quantum dot (QD) photodetectors consist of solution-processed QDs. Cross
      talk between a pair of closely positioned QD photodetectors was measured. Devices
      with 200 nm spacing exhibit low crosstalk of 8.4%. A single QD photodetector also
      shows high sensitivity, with a lowest detectable optical intensity of 95.3
      fW/MUm2 achieved. The results show the potential of nanogap QD photodetectors for
      applications in high-density imaging/sensing arrays.

PMID- 22859114
TI  - Resonant bend loss in leakage channel fibers.
AB  - Leakage channel fibers, designed to suppress higher-order modes, demonstrate
      resonant power loss at certain critical radii of curvature. Outside the
      resonance, the power recovers to the levels offset by the usual mechanism of bend
      induced loss. Using C2 imaging, we experimentally characterize this anomaly and
      identify the corresponding physical mechanism as the radiative decay of the
      fundamental mode mediated by the resonant coupling to a cladding mode.

PMID- 22859115
TI  - The underaddressed optical multiple-input, multiple-output channel: capacity and
      outage.
AB  - We study an optical space-division multiplexed system where the number of modes
      that are addressed by the transmitter and receiver is allowed to be smaller than
      the total number of optical modes supported by the fiber. This situation will be
      of relevance if, for instance, fibers supporting more modes than can be processed
      with current multiple-input, multiple-output technology are deployed with the
      purpose of future-proof installation. We calculate the ergodic capacity and the
      outage probability of the link and study their dependence on the number of
      addressed modes at the transmitter and receiver.

PMID- 22859116
TI  - Color digital holography using a single monochromatic imaging sensor.
AB  - Color digital holography utilizing the Doppler effect is proposed. The time
      variation of holograms produced by superposing images at three wavelengths is
      recorded using a high-speed monochromatic imaging sensor. The complex amplitude
      at each wavelength can be extracted from frequency information contained in the
      Fourier transforms of the recorded holograms. An image of the object is
      reconstructed by the angular spectrum method. Reconstructed monochromatic images
      at the three wavelengths are combined to produce a color image for display.

PMID- 22859117
TI  - Synchronously pumped photonic crystal fiber-based optical parametric oscillator.
AB  - We report the development of a compact, tunable synchronously pumped photonic
      crystal fiber (PCF)-based optical parametric oscillator (FOPO). The oscillator is
      pumped using a gain-switched laser diode producing 220 ps pulses around 1062 nm,
      amplified in a ytterbium doped amplifier to peak powers of 3.5 kW. The FOPO
      produces anti-Stokes pulses at wavelengths between 757 and 773 nm, with durations
      of 150 ps at average output powers exceeding 290 mW. The output slope efficiency
      of the device varies with output wavelength from 1.9 to 6.0%.

PMID- 22859118
TI  - Adaptable Bayesian classifier for spatiotemporal nonparametric moving object
      detection strategies.
AB  - Electronic devices endowed with camera platforms require new and powerful machine
      vision applications, which commonly include moving object detection strategies.
      To obtain high-quality results, the most recent strategies estimate
      nonparametrically background and foreground models and combine them by means of a
      Bayesian classifier. However, typical classifiers are limited by the use of
      constant prior values and they do not allow the inclusion of additional
      spatiodependent prior information. In this Letter, we propose an alternative
      Bayesian classifier that, unlike those reported before, allows the use of
      additional prior information obtained from any source and depending on the
      spatial position of each pixel.

PMID- 22859119
TI  - Reflectance-based two-dimensional TiO2 photonic crystal liquid sensors.
AB  - We propose and experimentally demonstrate a reflectance-based photonic crystal
      (PC) liquid sensor. The PC is made of two-dimensional TiO2 nanopillar arrays.
      Such a reflectance-based structure with large functional area not only simplifies
      the optical guiding but also enhances the sensor signal. A linear shift of
      reflectance peaks is found for liquids with refractive indices varying from 1.333
      to 1.390 at wavelength near 1.5 MUm. Excellent agreement between measured values
      and the generated reflectance model at a fixed wavelength is obtained, indicating
      the high potential of these PC-based liquid sensors for biological and
      environmental applications.

PMID- 22859120
TI  - Development of an explicit algorithm for remote sensing estimation of chlorophyll
      a using symbolic regression.
AB  - The primary mission of ocean color remote sensing is to provide accurate marine
      bio-optical properties from satellite data. We propose a new algorithm that uses
      symbolic regression to estimate chlorophyll a (chl a) concentrations from remote
      sensing reflectance. We compared the accuracy and computational efficiency of the
      new algorithm to that of the explicit empirical algorithms (OC4v4 and OC4v6), and
      implicit algorithms based on neural networks or support vector machines (SVM).
      Results show that the accuracy of the symbolic regression algorithm is higher
      than that of the OC4 algorithms and comparable to that of implicit algorithms.
      The improvement is particularly important for high biomass areas (chl a >= 3 mg
      m(-3)) that are often found in optically complex waters. The computational
      efficiency of the explicit algorithm developed by symbolic regression is
      comparable to that of the two versions of OC4 algorithms and better than that of
      implicit algorithms based on SVM. With its good precision and fast processing,
      the symbolic regression algorithm is a powerful tool for remote sensing of chl a
      that could be used advantageously in the reprocessing of large datasets.

PMID- 22859121
TI  - Mechanism for spherical dome and microvoid formation in polycarbonate using
      nanojoule femtosecond laser pulses.
AB  - Spherical domes are created on the surface of polycarbonate samples, and
      microvoids are formed within the bulk using only a femtosecond oscillator with
      pulse energy of just 0.47 nJ. Size of spherical domes and shape of microvoids are
      controlled by changing the laser focus inside the material. Their formation is
      explained by a combination of heat accumulation and dome formation dynamics,
      where the dome acts as a microlens shifting the laser focus within the sample.
      The technique described here provides a simple avenue for fabricating smooth
      microlens arrays of various sizes and opens the possibility for direct
      fabrication of complex three-dimensional microfluidic channels in transparent
      materials.

PMID- 22859122
TI  - Analytical expression of pulse broadening in an arbitrary linear slow light
      medium.
AB  - We derive an analytical expression for the broadening of a Gaussian input pulse
      in an arbitrary linear slow light medium. The expression consists of two terms,
      one corresponding to amplitude broadening (low-pass filtering of the pulse
      bandwidth) and another corresponding to phase broadening (phase dispersion around
      the resonance). It is shown that for a Lorentzian gain profile, the amplitude
      broadening is dominant at small fractional delays. However, for large fractional
      delays, phase broadening is inevitably dominate.

PMID- 22859123
TI  - Spatial characterization of the response of a silica optical fiber to wideband
      ultrasound.
AB  - Optical fibers have long been recognized as a promising technology for remote
      sensing of ultrasound. Nonetheless, very little is known about the
      characteristics of their spatial response, which is significantly affected by the
      strong acoustic mismatches between the fiber and surrounding medium. In this
      Letter, a new method is demonstrated for wideband spatial acoustic
      characterization of optical fibers. The method is based on the excitation of a
      point-like acoustic source via the opto-acoustic effect, while a miniature fiber
      sensor is implemented by a pi-phase-shifted fiber Bragg grating. Despite the
      relative complexity of acoustic wave propagation in the fiber, its spatial
      sensitivity in the high frequency band (6-30 MHz) exhibited an orderly pattern,
      which can be described by a simple model. This property reveals new possibilities
      for high-performance imaging using fiber-based ultrasound sensors, where
      knowledge of the sensor's spatial sensitivity map is generally required.

PMID- 22859124
TI  - Quasi-three-level neodymium-doped yttrium aluminum garnet laser emitting at 885
      nm.
AB  - We present a diode-pumped quasi-three-level neodymium-doped yttrium aluminum
      garnet (Nd:YAG) laser at 885 nm, based on the 4F3/2-4I9/2 transition, generally
      used for a 946 nm emission. Combined with polarization components (Nd:YAG), the
      electro-optical crystal KH2PO4 (KDP) formed a Lyot filter in the cavity and
      compressed the available gain bandwidth. With an incident pump power of 9.2 W, a
      714 mW continuous-wave (CW) output at 885 nm was achieved, and the optical-to
      optical efficiency was 7.8%. With an adjustable voltage applied to the KDP
      crystal, the laser wavelength could be tuned from 885 nm to 884 nm. A
      simultaneous dual-wavelength Nd:YAG laser at 885 nm and 884 nm was also realized
      by adjusting the free spectral range of the Lyot filter. To our knowledge, it is
      the first study that has realized the tuning between the 884 and 885 nm lines and
      the simultaneous dual-wavelength CW laser operation at 885 nm and 884 nm.

PMID- 22859125
TI  - Quantifying tissue microvasculature with speckle variance optical coherence
      tomography.
AB  - In this Letter, we demonstrate high resolution, three-dimensional optical imaging
      of in vivo blood vessel networks using speckle variance optical coherence
      tomography, and the quantification of these images through the development of
      biologically relevant metrics using image processing and segmentation techniques.
      Extracted three-dimensional metrics include vascular density, vessel tortuosity,
      vascular network fractal dimension, and tissue vascularity. We demonstrate the
      ability of this quantitative imaging approach to characterize normal and tumor
      vascular networks in a preclinical animal model and the potential for
      quantitative, longitudinal vascular treatment response monitoring.

PMID- 22859126
TI  - Propagation of cross-spectral densities from spherical sources.
AB  - We show that the cross-spectral density in the far zone of a homogeneous
      spherical source can be described as a low-pass filtered version of that existing
      across the source surface. We prove that, to an excellent approximation, the
      corresponding filter with respect to a (normalized) spatial frequency xi has a
      functional structure of the form ?(1-xi2), for 0<=xi<=1. The cases of spatially
      incoherent and Lambertian sources are treated as significant examples.

PMID- 22859127
TI  - High power all-fibered femtosecond master oscillator power amplifier at 1.56 MUm.
AB  - Direct amplification of output from chirped pulse oscillator (CPO) to 3.3 W of
      average power (pulse energy of 118 nJ in 20 ps pulse duration before compression)
      was achieved in a properly designed cladding pumped large mode area Er-doped
      fiber. Various configurations of CPO cavity with different FWHM of output
      spectrum and pulse duration were investigated. Fourier limit compression with 480
      fs pulse duration and 32 kW peak power has been obtained for pulses with 14.8 nm
      FWHM spectrum. Subsequent nonlinear compression in a standard SMF-28 fiber
      yielded pulses as short as 145 fs.

PMID- 22859128
TI  - High-purity transmission of a slow light odd mode in a photonic crystal
      waveguide.
AB  - We demonstrate a novel scheme to control the excitation symmetry for an odd mode
      in a photonic crystal waveguide and investigate the spectral signature of this
      slow light mode. An odd-mode Mach-Zehnder coupler is introduced to transform mode
      symmetry and excite a high-purity odd mode with 20 dB signal contrast over the
      background. Assisted by a mixed-mode Mach-Zehnder coupler, slow light mode
      beating can be observed and is utilized to determine the group index of this odd
      mode. With slow light enhancement, this odd mode can help enable novel
      miniaturized devices such as one-way waveguides.

PMID- 22859129
TI  - Compact three-port optical two-dimensional photonic crystal-based circulator of W
      format.
AB  - A three-port optical circulator of W-format based on 2D photonic crystal is
      presented. This circulator is more compact as compared to the known one of the
      traditional Y-format. The W-circulator does not have rotational symmetry. As a
      consequence, the frequency responses for different port excitation are slightly
      different, as it is shown by symmetry analysis and by numerical simulations.

PMID- 22859130
TI  - A 1.16-MUm-radius disk cavity in a sunflower-type circular photonic crystal with
      ultrahigh quality factor.
AB  - We present a 1.16-MUm-radius disk cavity with ultrahigh quality (Q) factor by
      embedding the disk into a sunflower-type circular photonic crystal (CPC). The
      bandgap of the CPC reduces the bending loss of the whispering-gallery mode of the
      disk, leading to a simulated Q of 10(7), at least an order of magnitude higher
      than a bare disk of the same size. The design is experimentally verified with a
      record high loaded Q of 7.4*10(5) measured from an optimized device fabricated on
      a silicon-on-insulator substrate.

PMID- 22859131
TI  - Absolute surface figure testing by shift-rotation method using Zernike
      polynomials.
AB  - In surface figure testing, most of them are relative tests, and the reference
      surface usually limits the accuracy of test results. Absolute calibration is one
      of the most important and efficient techniques to reach subnanometer accuracy in
      surface figure testing. An absolute testing method, a shift-rotation method using
      Zernike polynomials, is presented, which can be used to calibrate both flat and
      spherical surfaces (concave or convex). Calibration contains at least three
      position measurements: one basic position, one rotation, and one lateral shift of
      the test surface. Experiments show that the repeatability of this method is 0.13
      nm RMS, and pixel-to-pixel comparison with the two-sphere method is 0.2 nm RMS.

PMID- 22859132
TI  - Reshaping the trajectory and spectrum of nonlinear Airy beams.
AB  - We demonstrate theoretically and experimentally that a finite Airy beam changes
      its trajectory while maintaining its acceleration in nonlinear photorefractive
      media. During this process, the spatial spectrum reshapes dramatically, leading
      to negative (or positive) spectral defects on the initial spectral distribution
      under a self-focusing (or defocusing) nonlinearity.

PMID- 22859133
TI  - Narrowband phase sensitive fiber parametric amplifier.
AB  - We describe a widely tunable phase sensitive fiber amplifier, based on narrowband
      parametric amplification in dispersion shifted fiber. Using a fiber with a zero
      dispersion wavelength of 1549 nm and a pump wavelength in the range of 1549 nm to
      1532 nm, we obtained phase sensitive amplification between 1344 nm and 1781 nm,
      for an overall wavelength range of 437 nm. The amplifier threshold power is 7 W,
      and the maximum gain is 50 dB at a pump peak power of 25 W. The variance in gain
      due to phase sensitivity was measured to be up to 15 dB.

PMID- 22859134
TI  - Three-dimensional optical transfer of rotating beams.
AB  - Systems in which the point spread function (PSF) is a rotating beam have
      increasing use in three-dimensional (3D) microscopy and depth estimation. We
      analyze in several ways the 3D optical transfer function (OTF) of Gauss Laguerre
      modes and rotating beams. This is based on analysis of 3D OTFs of general
      aperture functions. Consequently, we suggest a criterion for depth resolution
      based on an effective cutoff of the axial frequency response. This criterion can
      be used to optimize PSFs explicitly and directly, to maximize axial resolution.

PMID- 22859135
TI  - Terahertz beat frequency generation from two-mode lasing operation of coupled
      microdisk laser.
AB  - We propose a coupled microdisk laser as a compact and tunable laser source for
      the generation of a coherent continuous-wave terahertz radiation by photomixing.
      Using the Schrodinger-Bloch model including the nonlinear effect of active
      medium, we find single-mode and two-mode lasings depending on the pumping
      strength. We explain the transitions of lasing modes in terms of resonant modes
      that are the solutions of the Schrodinger-Bloch model without active medium and
      nonlinear interaction. In particular, a two-mode lasing is shown to generate a
      terahertz oscillating frequency originating from the light beating of two nearly
      degenerated resonant modes with different symmetries.

PMID- 22859136
TI  - Common-path interferometer with a tri-window.
AB  - A common-path interferometer is proposed with a tri-window. It is built using a
      4f optical system with Ronchi ruling as a spatial filter. The input rectangular
      aperture is formed by three windows; the central window supports a phase object,
      and the other two are used for reference beams. Using an appropriate grating
      period relative to input aperture size, an interferogram containing three
      patterns can be obtained in the output plane. The object phase can then be
      reconstructed from the three patterns using just one interferogram. The
      experiments are carried out to demonstrate the feasibility and reliability of the
      proposed scheme.

PMID- 22859137
TI  - Acousto-optical coherence tomography with a digital holographic detection scheme.
AB  - Acousto-optical coherence tomography (AOCT) consists in using random phase jumps
      on ultrasound and light to achieve a millimeter resolution when imaging thick
      scattering media. We combined this technique with heterodyne off-axis digital
      holography. Two-dimensional images of absorbing objects embedded in scattering
      phantoms are obtained with a good signal-to-noise ratio. We study the impact of
      the phase modulation characteristics on the amplitude of the acousto-optic signal
      and on the contrast and apparent size of the absorbing inclusion.

PMID- 22859138
TI  - Narrow-bandwidth, mid-infrared, seeded optical parametric generation in 90
      degrees  phase-matched CdSiP2 crystal pumped by diffraction limited 500 ps pulses
      at 1064 nm.
AB  - Low-threshold, efficient optical parametric generation at ~6100 nm is
      demonstrated using CdSiP2 nonlinear crystal at 1 to 10 kHz repetition rates with
      relatively long 500 ps pump pulses at 1064 nm. Maximum single pulse energy of 8.7
      MUJ and average power of 79 mW are achieved for the idler. Seeding at the signal
      wavelength is employed using a distributed feedback laser diode, which enables
      approximately tenfold narrowing of the idler bandwidth down to less than 1 nm.

PMID- 22859139
TI  - Flexible quadrature amplitude modulation with semiconductor optical amplifier and
      electroabsorption modulator.
AB  - Optical quadrature amplitude modulation (QAM) is experimentally demonstrated with
      a low-complexity modulator based on a semiconductor optical amplifier and
      electroabsorption modulator. Flexible amplitude/phase format transmission is
      achieved. The applicability of octary QAM for coherent optical access networks
      with sustainable 3 Gb/s per-user bandwidth is investigated for a long reach of
      100 km, and its compatibility with a potentially high split is verified.

PMID- 22859140
TI  - Nonlinear optical grating diffraction in dye-doped blue-phase liquid crystals.
AB  - Low-power cw lasers are employed to study grating formation in blue-phase liquid
      crystals. We observed that undoped samples exhibit vanishingly small optical
      nonlinearities whereas methyl-red-dye doped samples produce strong nonlinear self
      diffraction effects. The nonlinearities are attributed to director axis
      reorientation, disorder, and lattice distortion by the laser-excited dye
      molecules. The magnitude of the observed intensity-dependent index coefficient is
      in the range of 10(-4)-10(-3) cm2/Watt.

PMID- 22859141
TI  - Continuous-wave terahertz in-line digital holography.
AB  - A terahertz (THz) in-line digital holography project has been proposed based on a
      CO2 pumped 2.52 THz continuous-wave laser and a pyroelectric-array camera used as
      the detector. The THz Gabor in-line digital holograms have been obtained and then
      the high resolution reconstruction of THz in-line digital holography was
      realized. The resolution of an in-line digital holography system has been tested
      by the use of a series of objects. High-quality and high-resolution reconstructed
      images have been obtained, and the real lateral resolution is higher than 0.2 mm.
      It can be inferred from the results that the THz Gabor in-line digital holography
      system has the abilities of real-time and high-resolution imaging.

PMID- 22859142
TI  - Ultrahigh laser pulse energy and power generation at 10 kHz.
AB  - This Letter presents results from a new master-oscillator, power-amplifier pulse
      burst laser system demonstrating ultrahigh pulse energies greater than 2.0
      J/pulse at 1064 nm with interpulse separations of 100 MUs (10 kHz) for burst
      durations of 100 pulses. Each pulse generates peak powers exceeding 130 MW and an
      average power of approximately 20 kW is generated over a 100-pulse-burst. Pulse
      energies decrease by less than 10% over a 100 sequential pulses, demonstrating
      negligible "droop" over long-duration pulse trains. Second-harmonic generation of
      532 nm with conversion efficiency greater than 50% is demonstrated for 100-pulse
      burst durations.

PMID- 22859143
TI  - Angular momentum properties of electromagnetic field transmitted through holey
      plasmonic vortex lenses.
AB  - We performed three-dimensional finite elements simulations of the optical
      response of holey plasmonic vortex lenses, i.e., spiral grooves milled on a thin
      gold film with a hole at the center. We focus in particular on the properties of
      the wave transmitted in the underlying half-space, which is shown to be a
      relevant part of the transmitted field. We find out that the angular momentum
      selection rule for this part of the field is different from the one for the
      transmitted plasmonic vortex, although closely related to the plasmonic
      interaction of the impinging wave with the chiral geometry.

PMID- 22859144
TI  - Giant Faraday and Kerr rotation with strained graphene.
AB  - Polarized electromagnetic waves passing through (reflected from) a dielectric
      medium parallel to a magnetic field undergo Faraday (Kerr) rotation of their
      polarization. Recently, Faraday rotation angles as much as 0.1 rad were observed
      for terahertz waves propagating through graphene over a SiC substrate. We show
      that the same effect is observable with the magnetic field replaced by an in
      plane strain field which induces a pseudomagnetic field in graphene. With two
      such sheets a rotation of pi/4 can be achieved, which is the required rotation
      for an optical diode. Similarly a Kerr rotation of 1/4 rad is predicted from a
      single reflection from a strained graphene sheet.

PMID- 22859145
TI  - Nonuniformly correlated light beams in uniformly correlated media.
AB  - The behavior of scalar beams with nonuniform correlations in isotropic random
      media is investigated. An example illustrates the fact that the off-axis
      intensity maximum formed in the transverse cross section of a nonuniformly
      correlated beam on propagation in free space is suppressed when it passes at
      sufficiently large distances from its source through the isotropic turbulent
      atmosphere.

PMID- 22859146
TI  - Simple, accurate formula for the average bit error probability of multiple-input
      multiple-output free-space optical links over negative exponential turbulence
      channels.
AB  - In this Letter we investigate the error performance of multiple-input multiple
      output free-space optical communication systems employing intensity
      modulation/direct detection and operating over strong atmospheric turbulence
      channels. Atmospheric-induced strong turbulence fading is modeled using the
      negative exponential distribution. For the considered system, an approximate yet
      accurate analytical expression for the average bit error probability is derived
      and an efficient method for its numerical evaluation is proposed. Numerically
      evaluated and computer simulation results are further provided to demonstrate the
      validity of the proposed mathematical analysis.

PMID- 22859147
TI  - Simulated and measured optical coherence tomography images of human enamel.
AB  - Optical coherence tomography images of human enamel were simulated and compared
      to measured images. A Monte Carlo code was implemented, which considered the
      microstructure of enamel. The prisms, the main scattering structures of the
      enamel, were described by oscillating cylinders whose scattering functions were
      obtained by solutions of Maxwell's equations. The essential features of the
      measured images including the Hunter-Schreger bands could be explained by the
      simulations.

PMID- 22859148
TI  - Multimode lasing from the microcavity of an octagonal quasi-crystal based on
      holographic polymer-dispersed liquid crystals.
AB  - An eightfold photonic quasi-crystal (PQC) sample is fabricated holographically
      using two-beam interference with multi-exposure based on polymer-dispersed liquid
      crystals. The transmission spectra from the finite-difference time-domain (FDTD)
      simulation prove the photonic stop band of the rotational symmetry structure of
      the sample. The resonant mode of the circular microcavity formed in the PQC is
      calculated. Amplified spontaneous emission and multimode lasing action are
      demonstrated from the pumped laser-dye-doped PQC microcavity using a Q-switched
      neodymium-doped yttrium aluminum garnet (Nd:YAG) pulse laser.

PMID- 22859149
TI  - Effect of the orientation of the optic axis on simulated scattering matrix
      elements of small birefringent particles.
AB  - We study how the orientation of the optic axis affects single-scattering
      properties for small, birefringent calcite particles simulated using DDSCAT
      7.1.1. We consider two irregular model particles, a flake and a rhomboid, in
      either a (i) fixed or (ii) random orientation. Simulations are performed for
      three volume-equivalent radii of 0.1, 0.45, and 1.0 MUm. For each target, we
      repeat the computations for three sets of orientations of the optic axis. When a
      fixed spatial orientation of the target is considered, the simulations are
      significantly affected by the orientation of the optic axis. However, the effect
      is considerably weaker when assuming the same targets in random spatial
      orientation.

PMID- 22859150
TI  - Experimental demonstration of free-space optical vortex transmutation with
      polygonal lenses.
AB  - Vortex transmutation was predicted to take place when vortices interact with
      systems possessing discrete rotational symmetries of finite order [Phys. Rev.
      Lett.95, 123901 (2005)]. Here we report what is believed to be the first
      experimental demonstration of vortex transmutation. We show that in free space,
      by simply inserting polygonal lenses into the optical path, the central vorticity
      of a coaxially incident optical vortex can be changed following the modular
      transmutation rule. We generate the wavefront at the exit face of the lenses with
      computer generated holograms and measure the output vorticity using the
      interference patterns at the focal plane. The results agree well with theoretical
      predictions.

PMID- 22859151
TI  - Optomechanical nanoantenna.
AB  - We introduce optomechanical nanoantennae, which show dramatic changes in
      scattering properties by minuscule changes in geometry. These structures are very
      compact, with a volume 500 times smaller than free-space optical wavelength
      volume. This deep subwavelength geometry leads to high speed and low switching
      power. The bandwidth of the device is about 4.4 GHz, with a switching energy of
      only 35 pJ. Such antenna structures could lead to compact and high-speed all
      optical nanoswitches.

PMID- 22859152
TI  - Active spectral filtering through turbid media.
AB  - We demonstrate controlled wavelength-dependent light focusing through turbid
      media using wavefront shaping. Due to the dispersion caused by multiple light
      scattering, light propagation through turbid media can be independently
      controlled between different wavelengths. Foci with various wavelengths can be
      generated by applying different optimized wavefronts to a highly scattering
      layer. Given the linearity of the transmission matrix, multiple foci with
      different wavelengths can also be simultaneously constructed.

PMID- 22859153
TI  - Polarization-independent guided-mode resonance filter with cross-integrated
      waveguide resonators.
AB  - A cavity-resonator-integrated guided-mode resonance filter (CRIGF) has been
      proposed and investigated in order to realize high-efficiency narrowband
      reflection with a small aperture. The CRIGF consists of a grating coupler
      integrated in a cavity resonator constructed by a pair of distributed Bragg
      reflectors on a thin-film waveguide. This time, orthogonally crossed integration
      of two CRIGFs was demonstrated in order to obtain polarization-independent
      reflection spectrum. An SiO2-based device with 10 MUm aperture was designed and
      fabricated for around 850 nm wavelength operation, and narrowband polarization
      independent reflection was confirmed experimentally.

PMID- 22859154
TI  - On the quantum-channel capacity for orbital angular momentum-based free-space
      optical communications.
AB  - Inspired by recent demonstrations of orbital angular momentum-(OAM)-based single
      photon communications, we propose two quantum-channel models: (i) the
      multidimensional quantum-key distribution model and (ii) the quantum
      teleportation model. Both models employ operator-sum representation for Kraus
      operators derived from OAM eigenkets transition probabilities. These models are
      highly important for future development of quantum-error correction schemes to
      extend the transmission distance and improve date rates of OAM quantum
      communications. By using these models, we calculate corresponding quantum-channel
      capacities in the presence of atmospheric turbulence.

PMID- 22859155
TI  - Linear up-conversion of orbital angular momentum.
AB  - We experimentally demonstrated that infrared light imprinted with orbital angular
      momentum (OAM) was linearly converted into visible light using four-wave mixing
      (FWM) via a ladder-type configuration in 85Rb atoms. Simultaneously, we
      theoretically simulated this linear conversion process, and the theoretical
      analysis was in reasonable agreement with the experimental results. A large
      single-photon detuning process was used to reduce the absorption of the atoms to
      the up-converted light and to avoid pattern formation in the FWM process. The
      multi-mode image linear conversion process is important for applications
      including image communications, astrophysics, and quantum information.

PMID- 22859156
TI  - Influence of polarization filtering on image registration precision in underwater
      conditions.
AB  - Underwater images often suffer from poor visibility due to photon scattering.
      However, in some cases, optical polarization filtering techniques can decrease
      the contribution of the scattered light and improve the visual image quality. In
      this Letter, the influence of these techniques for underwater image registration
      is analyzed, particularly when backscattered light is the main perturbation
      induced by the submarine environment. This analysis is performed using the Cramer
      Rao bound and relies on a standard image formation model, taking into account
      various kinds of noises.

PMID- 22859157
TI  - Phosphor in glasses with Pb-free silicate glass powders as robust color
      converting materials for white LED applications.
AB  - Phosphor-in-glass (PiG) typed robust color converters were fabricated using Pb
      free silicate glasses for high-power white LED applications. SiO2-B2O3
      RO(R=Ba,Zn) glass powder showed good sintering behavior and high visible
      transparency under the sintering condition of 750  degrees C for 30 min without
      noticeable interaction with phosphors. By simply changing the thickness of the
      PiG plate or mixing ratio of glass to Y3Al5O12:Ce3+ phosphor, CIE chromaticity
      coordinates of the LED can be easily controlled. Enhanced thermal quenching
      property of PiG compared to phosphor with conventional silicone resin suggests
      its prominent feasibility for high-power/high-brightness white LEDs.

PMID- 22859158
TI  - Enhanced harmonic generation by breaking the phase-matching symmetry.
AB  - We introduce two static methods to break the phase-matching symmetry in third
      harmonic generation with a focused Gaussian beam in the tight focusing limit,
      dramatically increasing the conversion efficiency and mode quality. Both rely on
      inhibiting harmonic generation immediately after the beam waist, preventing the
      near perfect cancellation of the third harmonic generation (THG) from before and
      after the focus. The first method involves placing a thin metal septum at the
      waist: the laser drills a small pinhole, which, in turn, disrupts the beam focus
      after the pinhole. The second method is based on placing a large chi(3) gas
      before the focus and a small chi(3) gas after the focus.

PMID- 22859159
TI  - Single-shot full-field interferometric polarimeter with an integrated calibration
      scheme.
AB  - A simple interferometric polarimeter with an integrated calibration scheme is
      proposed for accurate and fast mapping of the state of polarization (SOP).
      Conventional single-shot polarimeters that detect the amplitude and phase of
      orthogonally polarized field components by interferometry using Fourier fringe
      analysis suffers from errors caused by the imperfect reference beam and ambiguity
      in the spatial carrier frequency in the fringe pattern. In the proposed system,
      the integrated calibration scheme eliminates those error sources and enables
      accurate measurement of SOP without prior knowledge of the reference beam and the
      spatial carrier frequency.

PMID- 22859160
TI  - Mid-infrared virtually imaged phased array spectrometer for rapid and broadband
      trace gas detection.
AB  - We present and characterize a two-dimensional (2D) imaging spectrometer based on
      a virtually imaged phased array (VIPA) disperser for rapid, high-resolution
      molecular detection using mid-infrared (MIR) frequency combs at 3.1 and 3.8 MUm.
      We demonstrate detection of CH4 at 3.1 MUm with >3750 resolution elements
      spanning >80 nm with ~600 MHz resolution in a <10 MUs acquisition time. In
      addition to broadband detection, we also demonstrate rapid, time-resolved single
      image detection by capturing dynamic concentration changes of CH4 at a rate of
      ~375 frames per second. Changes in absorption above the noise floor of 5*10(-4)
      are readily detected on the millisecond time scale, leading to important future
      applications such as real-time monitoring of trace gas concentrations and
      detection of reactive intermediates.

PMID- 22859161
TI  - All-fiber Kerr cell.
AB  - An all-fiber nanosecond Kerr light gate is described that was constructed using
      microstructured fibers. The switching voltage for a 20 cm long device is as low
      as Vpi~85 V at a 1.06 MUm wavelength. The device is fully spliced. The active
      element is a three-hole fiber provided with internal electrodes in the side-holes
      and a liquid core of nitrobenzene, which is fully enclosed. This work allows the
      exploiting of electrically driven liquid-core fibers and demonstrated the removal
      of the major limitations of Kerr cells in the past, allowing for integration,
      safe use, and relatively low switching voltage.

PMID- 22859162
TI  - Three-dimensional spatiotemporal pulse characterization with an acousto-optic
      pulse shaper and a Hartmann-Shack wavefront sensor.
AB  - We demonstrate a simplified arrangement for spatiotemporal ultrashort pulse
      characterization called Hartmann-Shack assisted, multidimensional, shaper-based
      technique for electric-field reconstruction. It employs an acousto-optic pulse
      shaper in combination with a second-order nonlinear crystal and a Hartmann-Shack
      wavefront sensor. The shaper is used as a tunable bandpass filter, and the
      wavefronts and intensities of quasimonochromatic spectral slices of the pulse are
      obtained using the Hartmann-Shack wavefront sensor. The wavefronts and
      intensities of the spectral slices are related to one another using shaper
      assisted frequency-resolved optical gating measurements, performed at particular
      points in the beam. This enables a three-dimensional reconstruction of the
      amplitude and phase of the pulse. We present some example pulse measurements and
      discuss the operating parameters of the device.

PMID- 22859163
TI  - Emission amplification by sumanene nanocrystals in an onigiri-type organic
      organic assembly.
AB  - Core-shell assemblies of nanocrystals of sumanene (shell) and sumanenetrione
      (core) resembling onigiri (filled Japanese rice balls) were fabricated by
      stepwise reprecipitation. Optical properties of the onigiri-type assemblies
      showed that emissions from the core sumanenetrione nanocrystals were amplified
      through energy transfer from the shell sumanene nanocrystals through the
      nanocrystalline interface.

PMID- 22859164
TI  - Marching orders.

PMID- 22859165
TI  - Unfortunate oversight.

PMID- 22859166
TI  - The time is right to confront misconduct.

PMID- 22859177
TI  - Cancer stem cells tracked.

PMID- 22859178
TI  - FDA's claims over stem cells upheld.

PMID- 22859179
TI  - Officials act to secure cattle-plague virus.

PMID- 22859180
TI  - 7 minutes of terror.

PMID- 22859181
TI  - Lawsuit challenges anti-ageing claims.

PMID- 22859182
TI  - Geneticists eye the potential of arXiv.

PMID- 22859184
TI  - Science funding: Duel to the death.

PMID- 22859185
TI  - Human cycles: History as science.

PMID- 22859186
TI  - NASA: Let academia lead space science.

PMID- 22859190
TI  - Water: Improve access to sanitation in China.

PMID- 22859191
TI  - Higgs boson: Budget cuts leave US science lagging.

PMID- 22859192
TI  - Ecology: Bat deaths from wind turbine blades.

PMID- 22859193
TI  - Population: Better lives, not just contraceptives.

PMID- 22859195
TI  - Palaeontology: An insect to fill the gap.

PMID- 22859196
TI  - Earth science: The balance of the carbon budget.

PMID- 22859197
TI  - Drug discovery: Kill the messenger where it lives.

PMID- 22859199
TI  - Alzheimer's disease: A protective mutation.

PMID- 22859200
TI  - Systems biology: A cell in a computer.

PMID- 22859201
TI  - Quantum phase transition in a resonant level coupled to interacting leads.
AB  - A Luttinger liquid is an interacting one-dimensional electronic system, quite
      distinct from the 'conventional' Fermi liquids formed by interacting electrons in
      two and three dimensions. Some of the most striking properties of Luttinger
      liquids are revealed in the process of electron tunnelling. For example, as a
      function of the applied bias voltage or temperature, the tunnelling current
      exhibits a non-trivial power-law suppression. (There is no such suppression in a
      conventional Fermi liquid.) Here, using a carbon nanotube connected to resistive
      leads, we create a system that emulates tunnelling in a Luttinger liquid, by
      controlling the interaction of the tunnelling electron with its environment. We
      further replace a single tunnelling barrier with a double-barrier, resonant-level
      structure and investigate resonant tunnelling between Luttinger liquids. At low
      temperatures, we observe perfect transparency of the resonant level embedded in
      the interacting environment, and the width of the resonance tends to zero. We
      argue that this behaviour results from many-body physics of interacting
      electrons, and signals the presence of a quantum phase transition. Given that
      many parameters, including the interaction strength, can be precisely controlled
      in our samples, this is an attractive model system for studying quantum critical
      phenomena in general, with wide-reaching implications for understanding quantum
      phase transitions in more complex systems, such as cold atoms and strongly
      correlated bulk materials.

PMID- 22859202
TI  - A Newtonian approach to extraordinarily strong negative refraction.
AB  - Metamaterials with negative refractive indices can manipulate electromagnetic
      waves in unusual ways, and can be used to achieve, for example, sub-diffraction
      limit focusing, the bending of light in the 'wrong' direction, and reversed
      Doppler and Cerenkov effects. These counterintuitive and technologically useful
      behaviours have spurred considerable efforts to synthesize a broad array of
      negative-index metamaterials with engineered electric, magnetic or optical
      properties. Here we demonstrate another route to negative refraction by
      exploiting the inertia of electrons in semiconductor two-dimensional electron
      gases, collectively accelerated by electromagnetic waves according to Newton's
      second law of motion, where this acceleration effect manifests as kinetic
      inductance. Using kinetic inductance to attain negative refraction was
      theoretically proposed for three-dimensional metallic nanoparticles and seen
      experimentally with surface plasmons on the surface of a three-dimensional metal.
      The two-dimensional electron gas that we use at cryogenic temperatures has a
      larger kinetic inductance than three-dimensional metals, leading to
      extraordinarily strong negative refraction at gigahertz frequencies, with an
      index as large as -700. This pronounced negative refractive index and the
      corresponding reduction in the effective wavelength opens a path to
      miniaturization in the science and technology of negative refraction.

PMID- 22859203
TI  - Increase in observed net carbon dioxide uptake by land and oceans during the past
      50 years.
AB  - One of the greatest sources of uncertainty for future climate predictions is the
      response of the global carbon cycle to climate change. Although approximately one
      half of total CO(2) emissions is at present taken up by combined land and ocean
      carbon reservoirs, models predict a decline in future carbon uptake by these
      reservoirs, resulting in a positive carbon-climate feedback. Several recent
      studies suggest that rates of carbon uptake by the land and ocean have remained
      constant or declined in recent decades. Other work, however, has called into
      question the reported decline. Here we use global-scale atmospheric CO(2)
      measurements, CO(2) emission inventories and their full range of uncertainties to
      calculate changes in global CO(2) sources and sinks during the past 50 years. Our
      mass balance analysis shows that net global carbon uptake has increased
      significantly by about 0.05 billion tonnes of carbon per year and that global
      carbon uptake doubled, from 2.4 +/- 0.8 to 5.0 +/- 0.9 billion tonnes per year,
      between 1960 and 2010. Therefore, it is very unlikely that both land and ocean
      carbon sinks have decreased on a global scale. Since 1959, approximately 350
      billion tonnes of carbon have been emitted by humans to the atmosphere, of which
      about 55 per cent has moved into the land and oceans. Thus, identifying the
      mechanisms and locations responsible for increasing global carbon uptake remains
      a critical challenge in constraining the modern global carbon budget and
      predicting future carbon-climate interactions.

PMID- 22859204
TI  - Persistent near-tropical warmth on the Antarctic continent during the early
      Eocene epoch.
AB  - The warmest global climates of the past 65 million years occurred during the
      early Eocene epoch (about 55 to 48 million years ago), when the Equator-to-pole
      temperature gradients were much smaller than today and atmospheric carbon dioxide
      levels were in excess of one thousand parts per million by volume. Recently the
      early Eocene has received considerable interest because it may provide insight
      into the response of Earth's climate and biosphere to the high atmospheric carbon
      dioxide levels that are expected in the near future as a consequence of unabated
      anthropogenic carbon emissions. Climatic conditions of the early Eocene
      'greenhouse world', however, are poorly constrained in critical regions,
      particularly Antarctica. Here we present a well-dated record of early Eocene
      climate on Antarctica from an ocean sediment core recovered off the Wilkes Land
      coast of East Antarctica. The information from biotic climate proxies (pollen and
      spores) and independent organic geochemical climate proxies (indices based on
      branched tetraether lipids) yields quantitative, seasonal temperature
      reconstructions for the early Eocene greenhouse world on Antarctica. We show that
      the climate in lowland settings along the Wilkes Land coast (at a palaeolatitude
      of about 70 degrees  south) supported the growth of highly diverse, near-tropical
      forests characterized by mesothermal to megathermal floral elements including
      palms and Bombacoideae. Notably, winters were extremely mild (warmer than 10 
      degrees C) and essentially frost-free despite polar darkness, which provides a
      critical new constraint for the validation of climate models and for
      understanding the response of high-latitude terrestrial ecosystems to increased
      carbon dioxide forcing.

PMID- 22859205
TI  - A complete insect from the Late Devonian period.
AB  - After terrestrialization, the diversification of arthropods and vertebrates is
      thought to have occurred in two distinct phases, the first between the Silurian
      and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago),
      and the second characterized by the emergence of numerous new major taxa, during
      the Late Carboniferous period (after 345 Myr ago). These two diversification
      periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and
      arthropod gap (385-325 Myr ago), which could be due to preservational artefact.
      Although a recent molecular dating has given an age of 390 Myr for the
      Holometabola, the record of hexapods during the Early-Middle Devonian (411.5-391
      Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on
      fragmentary remains, which hinders the timing of this diversification. Indeed,
      although Devonian Archaeognatha are problematic, the Pragian of Scotland has
      given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic
      dicondylic, metapterygotan mandibles. The oldest, definitively winged insects are
      from the Serpukhovian stage (latest Early Carboniferous period). Here we report
      the first complete Late Devonian insect, which was probably a terrestrial
      species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not
      modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in
      the fossil record of Hexapoda, and demonstrates further a first Devonian phase of
      diversification for the Hexapoda, as in vertebrates, and suggests that the
      Pterygota diversified before and during Romer's gap.

PMID- 22859206
TI  - Defining the core Arabidopsis thaliana root microbiome.
AB  - Land plants associate with a root microbiota distinct from the complex microbial
      community present in surrounding soil. The microbiota colonizing the rhizosphere
      (immediately surrounding the root) and the endophytic compartment (within the
      root) contribute to plant growth, productivity, carbon sequestration and
      phytoremediation. Colonization of the root occurs despite a sophisticated plant
      immune system, suggesting finely tuned discrimination of mutualists and
      commensals from pathogens. Genetic principles governing the derivation of host
      specific endophyte communities from soil communities are poorly understood. Here
      we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than
      600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere
      and endophytic compartment microbiota of plants grown under controlled conditions
      in natural soils are sufficiently dependent on the host to remain consistent
      across different soil types and developmental stages, and sufficiently dependent
      on host genotype to vary between inbred Arabidopsis accessions. We describe
      different bacterial communities in two geochemically distinct bulk soils and in
      rhizosphere and endophytic compartments prepared from roots grown in these soils.
      The communities in each compartment are strongly influenced by soil type.
      Endophytic compartments from both soils feature overlapping, low-complexity
      communities that are markedly enriched in Actinobacteria and specific families
      from other phyla, notably Proteobacteria. Some bacteria vary quantitatively
      between plants of different developmental stage and genotype. Our rigorous
      definition of an endophytic compartment microbiome should facilitate controlled
      dissection of plant-microbe interactions derived from complex soil communities.

PMID- 22859207
TI  - Revealing structure and assembly cues for Arabidopsis root-inhabiting bacterial
      microbiota.
AB  - The plant root defines the interface between a multicellular eukaryote and soil,
      one of the richest microbial ecosystems on Earth. Notably, soil bacteria are able
      to multiply inside roots as benign endophytes and modulate plant growth and
      development, with implications ranging from enhanced crop productivity to
      phytoremediation. Endophytic colonization represents an apparent paradox of plant
      innate immunity because plant cells can detect an array of microbe-associated
      molecular patterns (also known as MAMPs) to initiate immune responses to
      terminate microbial multiplication. Several studies attempted to describe the
      structure of bacterial root endophytes; however, different sampling protocols and
      low-resolution profiling methods make it difficult to infer general principles.
      Here we describe methodology to characterize and compare soil- and root
      inhabiting bacterial communities, which reveals not only a function for
      metabolically active plant cells but also for inert cell-wall features in the
      selection of soil bacteria for host colonization. We show that the roots of
      Arabidopsis thaliana, grown in different natural soils under controlled
      environmental conditions, are preferentially colonized by Proteobacteria,
      Bacteroidetes and Actinobacteria, and each bacterial phylum is represented by a
      dominating class or family. Soil type defines the composition of root-inhabiting
      bacterial communities and host genotype determines their ribotype profiles to a
      limited extent. The identification of soil-type-specific members within the root
      inhabiting assemblies supports our conclusion that these represent soil-derived
      root endophytes. Surprisingly, plant cell-wall features of other tested plant
      species seem to provide a sufficient cue for the assembly of approximately 40% of
      the Arabidopsis bacterial root-inhabiting microbiota, with a bias for
      Betaproteobacteria. Thus, this root sub-community may not be Arabidopsis-specific
      but saprophytic bacteria that would naturally be found on any plant root or plant
      debris in the tested soils. By contrast, colonization of Arabidopsis roots by
      members of the Actinobacteria depends on other cues from metabolically active
      host cells.

PMID- 22859210
TI  - Models of grid cells and theta oscillations.

PMID- 22859212
TI  - Determining gene moderation of environmental risk factors for a mental disorder:
      a "perfect storm" of methodological problems.
AB  - For most of the twentieth century, the focus was on "nature" versus "nurture",
      i.e. genetic versus environmental effects on disorders. Now it is increasingly
      recognized that a disorder may reflect genes and environments "working together".
      A gene may moderate an environmental risk factor, it may be mediated by an
      environmental risk factor. The environmental risk factor may be proxy to the
      gene, and the two may be independent risk factors. Which of these situations
      pertain influences both subsequent research and clinical and policy decision
      making. However, recent meta-analyses attempting to confirm the Caspi et al.
      (Science, 301, 386-389, 2003) hypothesis indicate that the methodological issues
      relating to establishing specifically a moderating effect of a gene on an
      environmental factor are not well understood. The discussion here concerns the
      definition of "moderator", how it is distinct from other ways in which gene and
      environment can "work together", the methods needed to establish such a
      moderator, and the public health significance of such efforts.

PMID- 22859208
TI  - Targeting nuclear RNA for in vivo correction of myotonic dystrophy.
AB  - Antisense oligonucleotides (ASOs) hold promise for gene-specific knockdown in
      diseases that involve RNA or protein gain-of-function effects. In the hereditary
      degenerative disease myotonic dystrophy type 1 (DM1), transcripts from the mutant
      allele contain an expanded CUG repeat and are retained in the nucleus. The mutant
      RNA exerts a toxic gain-of-function effect, making it an appropriate target for
      therapeutic ASOs. However, despite improvements in ASO chemistry and design,
      systemic use of ASOs is limited because uptake in many tissues, including
      skeletal and cardiac muscle, is not sufficient to silence target messenger RNAs.
      Here we show that nuclear-retained transcripts containing expanded CUG (CUG(exp))
      repeats are unusually sensitive to antisense silencing. In a transgenic mouse
      model of DM1, systemic administration of ASOs caused a rapid knockdown of
      CUG(exp) RNA in skeletal muscle, correcting the physiological, histopathologic
      and transcriptomic features of the disease. The effect was sustained for up to 1
      year after treatment was discontinued. Systemically administered ASOs were also
      effective for muscle knockdown of Malat1, a long non-coding RNA (lncRNA) that is
      retained in the nucleus. These results provide a general strategy to correct RNA
      gain-of-function effects and to modulate the expression of expanded repeats,
      lncRNAs and other transcripts with prolonged nuclear residence.

PMID- 22859213
TI  - Electro-switchable polydimethylsiloxane-based optofluidics.
AB  - We report on the fabrication and characterization of a new generation of electro
      switchable optofluidic devices based on flexible substrates, combined with the
      extraordinary properties of reconfigurable soft-materials. A conductive
      polydimethylsiloxane microstructure has been first sputtered with an Indium Tin
      Oxide (ITO) layer and then functionalized with an amorphous film of SiO(x). Then,
      the "layer" by "layer" microstructure has been infiltrated with an anisotropic
      and reconfigurable fluid (Nematic Liquid Crystal, NLC). The sample has been
      characterized in terms of morphological, optical and electro-optical properties:
      the soft-conductive microstructure exhibits a uniform and regular morphology,
      even after testing with mechanical stretching and deformations. Combination of
      the conductive ITO with the functionalization film (which has been employed for
      inducing in-plane alignment of NLC molecules) enables us to carry out a series of
      optical and electro-optical experiments; these confirm excellent properties in
      terms of a reconfigurable device and a diffractive element as well.

PMID- 22859214
TI  - Photopheresis (extracorporeal photochemotherapy).
AB  - Photopheresis is a form of phototherapy where specialized equipment is used to
      isolate a leukocyte fraction from the peripheral blood which is then exposed to
      photoactivated 8-methoxypsoralen and reinfused into the patient. At the time of
      its invention the treatment was conceptually based on the hypothesis of T cell
      vaccination, i.e. the observation in experimental studies that exposure of the
      immune system to physically modified T cell clones leads to a specific inhibition
      of T cell mediated autoimmunity. Consequently, photopheresis has been tried in a
      variety of conditions where T cells are thought to have a critical role and has
      shown clinical efficacy mainly in variants of cutaneous T cell lymphomas, graft
      versus-host disease, systemic sclerosis, in solid organ transplant rejection and
      Crohn's disease. Evidence has accumulated that alterations in antigen
      presentation and the generation of regulatory T cells are induced by
      photopheresis and might be related to the observed clinical effects. Summarizing
      what has been published in the 25 years since its introduction into the clinic,
      photopheresis to date has found its place in the treatment of the above mentioned
      conditions as a well tolerated treatment option that can safely be combined with
      other established modalities. It can be expected that further research will help
      refine its clinical indications and close the gaps that still exist in our
      knowledge on when, how, and why photopheresis works.

PMID- 22859215
TI  - Multi-electron dissociative ionization of clusters under picosecond and
      femtosecond laser irradiation: the case of alkyl-halide clusters.
AB  - The multi-electron dissociative ionization (MEDI) of alkyl-halide clusters
      induced by 35 ps (at 266, 532 and 1064 nm) and 20 fs (at 400 and 800 nm) laser
      pulses is reported. In most cases, the MEDI of clusters is observed at
      substantially lower laser intensities than those reported for the monomer
      molecules, while the fragment ions are released with higher kinetic energies.
      From the comparative analysis of the experimental data, is concluded that the
      increase of molecular chain and/or the presence of a lighter halogen (I, Br, Cl)
      in the molecular skeleton results in the increase of the laser intensity
      thresholds for the appearance of the singly and multiply charged fragment ions.
      As far as the angular distributions of the ejected ions are concerned, they are
      found to be dependent on the laser pulse duration. For the observed experimental
      data, a physical mechanism is proposed, based on the combined action of the laser
      and the electric field created within the clusters after their single ionization.

PMID- 22859216
TI  - Loss of immunity-supported senescence enhances susceptibility to hepatocellular
      carcinogenesis and progression in Toll-like receptor 2-deficient mice.
AB  - Hepatocellular carcinoma (HCC) is a complication at the endstage of chronic
      inflammatory liver diseases with dismal prognosis. Targeting of Toll-like
      receptor (TLR) 2 attenuates tumor metastases; we hypothesized that blocking TLR2
      might also play a crucial role in reducing hepatocarcinogenesis. Surprisingly, we
      found that the genetic deletion of TLR2 increased susceptibility to
      diethylnitrosamine (DEN), a genotoxic carcinogen that can induce HCC. Indeed,
      TLR2-deficient mice showed a significant increase in carcinogenesis and
      progression of HCC as indicated by increases in tumor nodule size, tumor volume,
      and animal death. The enhanced susceptibility to DEN-induced HCC was associated
      with a broad-spectrum reduction in the immune response to DEN-induced liver
      injury. We found that TLR2 deficiency caused a decrease in the infiltration of
      macrophages and an attenuation of apoptosis signal regulating kinase 1 (ASK1) /
      p38 mitogen-activated protein kinase (p38 MAPK) / nuclear factor kappa B (NF
      kappaB) signaling, which led to a decrease in the expression of interferon-gamma
      (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)
      1alpha/beta, IL-6, and Cxcl-2 as well as suppression of autophagy flux and
      increases in oxidative stress and p62 aggregation in liver tissue. The defects in
      immune networks resulted in suppressed p21- and p16/pRb-dependent senescence,
      which caused an increase in proliferation and a decrease in apoptotic and
      autophagy-associated cell death in mouse livers. Restoring cellular senescence
      and autophagy flux by treating TLR2-deficient mice with IFN-gamma, a T helper 1
      (Th1) cytokine and positive modulator of senescence and autophagy, could
      attenuate the carcinogenesis and progression of HCC associated with TLR2
      deficient animals. CONCLUSION: The loss of immune networks supporting cellular
      senescence and autophagy flux is attributed to enhanced susceptibility to DEN
      induced hepatocellular carcinogenesis and progression in TLR2-deficient mice.
      These findings may be used to prevent the development of liver cancer.

PMID- 22859217
TI  - Transplantation of bone marrow-derived endothelial progenitor cells attenuates
      myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin
      induced diabetic rats.
AB  - Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle and
      the third most common cause of heart failure. In the present study, we evaluated
      the effects of bone marrow-derived endothelial progenitor cell (EPC)
      transplantation on the development of DCM in a streptozotocin (STZ)-induced
      diabetic rat model. Ex vivo generated, characterized and cultivated rat EPCs were
      identified by flow cytometry of their surface markers. EPCs were transplanted
      intravenously into rats through the tail vein 6 weeks after they were challenged
      with STZ and the rats were sacrificed 4 weeks later. Before sacrifice, left
      ventricular (LV) catheterization was performed to evaluate the cardiac function.
      Myocardium sections were stained with Masson's trichrome staining to investigate
      myocardial collagen contents. Fibrosis-, apoptosis- and oxidative stress-related
      gene expressions were analyzed by western blot analysis. Transplantation of EPCs
      alleviated the impaired cardiac function associated with diabetes and decreased
      the collagen volume in diabetic myocardium resulting in improved cardiac
      function. Furthermore, EPC transplantation decreased the expression of type I
      collagen, Bax, caspase-3 and p67phox, while increasing the expression of Bcl-2
      and manganese superoxide dismutase (MnSOD). Taken together, our results suggest
      that transplantation of EPCs improved cardiac function in the rat DCM model,
      likely through inhibition of cardiomyocyte apoptosis and attenuating myocardial
      fibrosis.

PMID- 22859218
TI  - Synthesis, structure and luminescence properties of Cu(II), Zn(II) and Cd(II)
      complexes with 4'-terphenylterpyridine.
AB  - The complexes [M(tptpy)(2)](ClO(4))(2) (M = Zn(II) (1), Cd(II) (2), and Cu(II)
      (3)); tptpy = 4'-[1,1':4',1'']terphenyl-4''-yl-[2,2':6',2'']terpyridine = 4'
      terphenylterpyridine) have been synthesized, structurally characterized by X-ray
      crystallography and subjected to preliminary luminescence studies. In the
      crystalline state, all the metal ions have an N(6) coordination sphere of
      distorted octahedral geometry and the structures of the Zn(II) and Cd(II)
      complexes are isomorphous but differ from that of the Cu(II) complex, which also
      differs from the other two in that it is non-emissive. The structure
      determinations show that aromatic-aromatic interactions involving both the
      terpyridine heads and the terphenyl tails are important factors influencing the
      crystalline array. The emission spectra of the Zn(II) and Cd(II) complexes are
      very similar and show a considerable red-shift of the emission maximum compared
      to that of the free ligand.

PMID- 22859219
TI  - A facile photo-induced synthesis of COOH functionalized meso-macroporous carbon
      films and their excellent sensing capability for aromatic amines.
AB  - A simple photo-induced approach is developed for the preparation of COOH
      functionalized meso-macroporous carbon films with tunable pores without using any
      inorganic mesoporous silica templates, which show excellent sensing selectivity
      for aniline and the selectivity can be enhanced upon increasing COOH functional
      groups.

PMID- 22859220
TI  - Modular microfluidic system fabricated in thermoplastics for the strain-specific
      detection of bacterial pathogens.
AB  - The recent outbreaks of a lethal E. coli strain in Germany have aroused renewed
      interest in developing rapid, specific and accurate systems for detecting and
      characterizing bacterial pathogens in suspected contaminated food and/or water
      supplies. To address this need, we have designed, fabricated and tested an
      integrated modular-based microfluidic system and the accompanying assay for the
      strain-specific identification of bacterial pathogens. The system can carry out
      the entire molecular processing pipeline in a single disposable fluidic cartridge
      and detect single nucleotide variations in selected genes to allow for the
      identification of the bacterial species, even its strain with high specificity.
      The unique aspect of this fluidic cartridge is its modular format with task
      specific modules interconnected to a fluidic motherboard to permit the selection
      of the target material. In addition, to minimize the amount of finishing steps
      for assembling the fluidic cartridge, many of the functional components were
      produced during the polymer molding step used to create the fluidic network. The
      operation of the cartridge was provided by electronic, mechanical, optical and
      hydraulic controls located off-chip and packaged into a small footprint
      instrument (1 ft(3)). The fluidic cartridge was capable of performing cell
      enrichment, cell lysis, solid-phase extraction (SPE) of genomic DNA, continuous
      flow (CF) PCR, CF ligase detection reaction (LDR) and universal DNA array
      readout. The cartridge was comprised of modules situated on a fluidic
      motherboard; the motherboard was made from polycarbonate, PC, and used for cell
      lysis, SPE, CF PCR and CF LDR. The modules were task-specific units and performed
      universal zip-code array readout or affinity enrichment of the target cells with
      both made from poly(methylmethacrylate), PMMA. Two genes, uidA and sipB/C, were
      used to discriminate between E. coli and Salmonella, and evaluated as a model
      system. Results showed that the fluidic system could successfully identify
      bacteria in <40 min with minimal operator intervention and perform strain
      identification, even from a mixed population with the target of a minority. We
      further demonstrated the ability to analyze the E. coli O157:H7 strain from a
      waste-water sample using enrichment followed by genotyping.

PMID- 22859222
TI  - The new face of fillers: a multi-specialty CME initiative: supplement part II of
      II.

PMID- 22859221
TI  - beta-catenin involvement in arsenite-induced VEGF expression in neuroblastoma SH
      SY5Y cells.
AB  - Arsenic is a widespread contaminant in the environment especially in drinking
      water. Although it is a known carcinogen in human, the mechanism by which arsenic
      induces carcinogenesis is not well understood. Among several effects of arsenic,
      it has been suggested that arsenic-induced vascular endothelial growth factor
      (VEGF) expression plays a critical role in arsenic carcinogenesis. In the present
      study, we demonstrated that arsenite induced VEGF expression in neuroblastoma SH
      SY5Y cells without induction of HIF-1alpha, a well-known transcriptional
      activator for VEGF suggesting that arsenite-induced VEGF expression in SH-SY5Y
      cells may not require HIF-1alpha activation. It has been reported that VEGF
      expression is regulated by multiple transcription factors including beta-catenin.
      We therefore investigated whether beta-catenin was involved in arsenite-induced
      VEGF expression in SH-SY5Y cells. Treatment of arsenite caused beta-catenin
      accumulation in the nucleus. Additionally, arsenite treatment decreased the
      activity of GSK3, an enzyme that phosphorylates and targets beta-catenin for
      degradation by proteasome, without activation of its upstream kinase, Akt.
      Inhibition of PI3K/Akt which negatively regulates GSK3 activity by LY294002
      resulted in a decrease in arsenite-mediated beta-catenin nuclear accumulation,
      and VEGF expression. These results suggested that beta-catenin plays a role in
      arsenite-induced VEGF in SH-SY5Y cells, and the induction of beta-catenin by
      arsenite is mediated by inhibition of GSK3 without activating its upstream kinase
      Akt.

PMID- 22859223
TI  - Fillers and the "three curves of youth".
AB  - A 40-year-old Asian female presented complaining of looking tired. She had no
      significant medical history and was in good health. She had received botulinum
      toxin injection in the glabellar area routinely over the last several years but
      had no history of injectable fillers.

PMID- 22859224
TI  - New and emerging concepts in soft tissue fillers: roundtable discussion.
AB  - In the years since the U.S. FDA approval in 2003 of the first hyaluronic acid
      (HA) filler, a number of other HA products have become available for use in the
      U.S., in addition to products composed of calcium hydroxylapatite (CaHA), poly-L
      lactic acid (PLLA) and polymethyl methacrylate (PMMA). This roundtable discussion
      between two US-based dermatologists, a European plastic surgeon, and a US-based
      plastic surgeon provides an overview of commonly used alloplastic filler products
      and examines how new strategies for soft tissue augmentation are developing as
      filler options continue to expand.

PMID- 22859225
TI  - Hyaluronic acid fillers on the horizon: roundtable discussion.
AB  - In this roundtable discussion, the physicochemical properties and potential
      clinical applications of two new ranges of hyaluronic acid fillers are reviewed.
      These fillers display enhanced tissue integration after implantation due to novel
      manufacturing processes, and one of the ranges is customized for specific
      clinical applications by variation of filler gel calibration and cross-linking.

PMID- 22859226
TI  - Racial and ethnic differences in skin aging: implications for treatment with soft
      tissue fillers.
AB  - Racial and ethnic differences in the age of onset, severity, and anatomical
      features of facial aging have been described. In addition, increased melanocyte
      lability and fibroblast reactivity are functional features that are
      characteristic of skin of color. These differences should be considered when
      treating patients with soft tissue fillers in order to achieve optimal results.
      Signs of facial aging in individuals with skin of color tend to be most
      pronounced in the periorbital and midface region with less prominent features of
      skin aging in the upper third of the face and a decreased tendency toward
      perioral rhytides and radial lip lines. As such, volumization of the midface
      while preserving individual and ethnic ideals of beauty is a key goal. Important
      treatment considerations include minimization of inflammation, epidermal injury,
      and bruising, which can lead to aesthetically displeasing sequelae.

PMID- 22859227
TI  - Blunt-tipped microcannulas for the injection of soft tissue fillers: a consensus
      panel assessment and recommendations.
AB  - As blunt injection microcannulas increase in popularity, clinicians may find it
      of value to have a systematic review of their current uses. This consensus
      document is derived from a roundtable discussion between a multi-specialty
      faculty comprising two U.S.-based dermatologists, one U.S.-based plastic surgeon,
      and one European cosmetic surgeon, all of whom were early adopters of blunt
      microcannulas for alloplastic fillers. The purpose of this consensus document is
      to provide an overview of the utility and clinical applications of blunt
      microcannulas, guidelines for their safe and efficacious use, and recommendations
      for the further evidence that needs to be accrued to substantiate the claims that
      have been made in regard to their superior safety profile and other benefits.

PMID- 22859228
TI  - Utilizing blunt-tipped cannulas in specific regions for soft-tissue augmentation.

PMID- 22859229
TI  - Blunt-tipped microcannulas--a personal perspective.

PMID- 22859230
TI  - Blunt-tipped microcannulas for filler injection: an ethical duty?

PMID- 22859231
TI  - The tower technique and vertical supraperiosteal depot technique: novel vertical
      injection techniques for volume-efficient subcutaneous tissue support and
      volumetric augmentation.
AB  - A 55-year-old Caucasian female with a past history of face-lifting surgery
      presented with early signs of soft tissue elastosis, volumetric deficiency in the
      periocular region, the nasolabial folds, the lips, and the lower face. Hyaluronic
      acid (HA) filler injections were performed with two novel vertical injection
      techniques that support and tense the subcutaneous connective tissue--the Tower
      Technique (TT) and the Vertical Supraperiosteal Depot Technique (VSDT). Vertical
      injection techniques are a volume-efficient means of delivering excellent, long
      lasting results and patient satisfaction with minimal recovery time and are
      appropriate for volumetric augmentation even in patients who have subdermal
      fibrosis due to previous facial surgery.

PMID- 22859233
TI  - Message from the guest editor.

PMID- 22859234
TI  - The safety of ustekinumab in psoriasis.
AB  - Ustekinumab is effective in the treatment of a variety of autoimmune conditions
      including psoriasis. As a relatively new therapeutic agent, its long-term effects
      are still under investigation. Short-term studies, however, have revealed
      ustekinumab to be generally well tolerated and safe. This article provides a
      comprehensive review of the pharmacokinetics of ustekinumab, its safety profile,
      adverse effects, and use in pregnancy. The effect of diabetes and prior
      immunosuppressant therapy is also addressed.

PMID- 22859235
TI  - JAK inhibitors in psoriasis: a promising new treatment modality.
AB  - BACKGROUND: Inflammatory cytokines play a crucial role in the pathophysiology of
      psoriasis. New therapies are targeting Janus kinases (JAKs), enzymes involved
      with transduction of cytokine receptor signaling. OBJECTIVE: Review the utility
      of JAK inhibitors in the treatment of psoriasis. METHODS: A review was performed
      using PubMed and Google to identify research relevant to the treatment of
      psoriasis using JAK inhibitors. RESULTS: In a CD18 mutant PL/J mouse model with T
      cell dependent psoriasiform skin disease, the JAK inhibitor R348 reduced skin
      inflammation, with reductions in CD4+, CD8+, and CD25+ T-cell infiltration and
      systemic decreases of IL-17, IL-19, IL-22, IL-23 and TNF-alpha. Two JAK
      inhibitors, CP-690,550 (tasocitinib) and INCB018424 (ruxolitinib), were effective
      in psoriasis clinical trials. In a phase 1, randomized, double-blind, dose
      escalation trial for plaque psoriasis, CP-690,050 led to improvements in
      Psoriatic Lesion Severity Sum score at doses greater than 5 mg. A phase 2 trial
      showed CP-690,050 administered at 2, 5, and 15 mg twice daily resulted in a 75%
      reduction in Psoriasis Area and Severity Index (PASI) in 25%, 40.8%, and 66.7% of
      patients, respectively, for moderate to severe psoriasis. A phase 3 study of CP
      690,550 for plaque psoriasis was begun in September 2010 (NCT01163253).
      INCB018424, another JAK inhibitor, was used topically at 3 doses (0.5%, 1%, 1.5%)
      in a phase 2B, double-blind, placebo-controlled trial, resulting in improved
      total lesion score, global assessment, and PASI for all doses. CONCLUSION: Janus
      Kinase inhibitors are promising potential therapeutic options for psoriasis.

PMID- 22859236
TI  - Digital videography assessment of patients' experiences using adapalene-benzoyl
      peroxide gel in the treatment of acne vulgaris.
AB  - BACKGROUND: Acne profoundly affects patients' lives, but the effect of treatment
      is not fully characterized. OBJECTIVE: The purpose of this study was to explore
      patients' experiences and viewpoints regarding treatment for mild to moderate
      acne vulgaris. METHODS: This was an open-label, single-center study of 30
      patients with mild to moderate acne vulgaris, treated with adapalene 0.1%/benzoyl
      peroxide 2.5% (adapalene-BPO gel) once daily for 12 weeks. An acne-specific
      quality of life questionnaire (Acne-QoL(c)) was conducted. Each subject's global
      assessment (SGA) was recorded at baseline and weeks 4, 8, and 12. Photographs
      were taken and video interviews were recorded. Local tolerability assessments and
      incidence of adverse events were documented. RESULTS: A statistically significant
      number of patients were clear/almost clear (treatment success) at week 12
      (P<.001). At week 12, patients experienced a 44.1% and 57.1% mean reduction in
      inflammatory and noninflammatory lesions, respectively. By week 12, 67% of the
      patients in the video population (n=27) believed they had achieved treatment
      success (P<.001). Patients reported higher Acne-QoL(c) scores at week 12 compared
      to baseline, indicating better quality of life after treatment with adapalene-BPO
      gel (P<.001 for all domains). No unexpected adverse or serious adverse events
      were reported. LIMITATIONS: This was an open-label study of 12 weeks duration.
      CONCLUSION: Overall, patients with mild to moderate acne treated with adapalene
      BPO gel showed significant improvement in disease severity and quality of life.
      The video recordings chronicled the patients' experiences throughout the
      treatment process.

PMID- 22859237
TI  - A randomized controlled study of combination therapy with alefacept and narrow
      band UVB phototherapy (UVB) for moderate to severe psoriasis: efficacy, onset,
      and duration of response.
AB  - BACKGROUND: Alefacept is an effective intermittent treatment for psoriasis that
      can provide long-lasting remissions. Combination therapy with narrow-band
      ultraviolet B (nbUVB) phototherapy may enhance treatment outcomes and accelerate
      the onset of clinical response. OBJECTIVE: To assess the efficacy of alefacept in
      combination with nbUVB phototherapy compared to alefacept alone in subjects with
      moderate to severe psoriasis. METHODS: Ninety-eight adults with moderate to
      severe psoriasis were randomized to treatment with alefacept 15 mg
      intramuscularly (i.m.) once weekly for 12 weeks alone or in combination with
      three times weekly nbUVB treatments in this prospective, open-label, assessor
      blinded, randomized, multicenter, parallel-group, 36-week study. RESULTS: A
      statistically significantly greater proportion of subjects in the alefacept plus
      nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to
      subjects in the alefacept alone arm (44.9% vs 22.5%, P=0.032). Secondary outcomes
      were also in favor of the alefacept plus nbUVB group, including the proportion of
      subjects achieving a Physician Global Assessment (PGA) score of clear or almost
      clear at any time during the study (59.2% vs 34.7%, P=0.026) and reduction in
      percent body surface area (BSA) involved with psoriasis at week 16 (13.4% vs
      8.0%, P<0.001). The onset of clinical response was significantly faster in the
      combination therapy group compared to monotherapy (mean time to PASI 75: 82 vs
      107 days, P=0.007). Both treatments were generally well tolerated. LIMITATIONS:
      Open-label, assessor-blinded study without a phototherapy-only treatment arm.
      CONCLUSION: The addition of nbUVB to treatment with alefacept significantly
      enhanced and accelerated the clinical benefits of alefacept therapy and was
      generally safe and well-tolerated.

PMID- 22859238
TI  - Treatment of nail psoriasis with TNF-alpha or IL12/23 inhibitors.
AB  - Nail psoriasis appears to be an important source of psoriatic morbidity through
      physical impairment, pain, and cosmetic disturbances. Conventional treatment is
      often unsatisfactory. A systematic review of studies reporting the effect of TNF
      alpha inhibitors and related drugs on nail psoriasis using the Nail Psoriasis
      Severity Index (NAPSI) as the outcome measure was therefore made. Data are
      available from randomized controlled trials (RCT) where NAPSI has been studied as
      a secondary outcome, as well as from case-series in which NAPSI has been the
      primary outcome studies suggest that adalimumab, briakinumab, etanercept,
      golimumab, infliximumab, and ustekinumab all improve NAPSI scores. No direct
      comparative RCTs are available in which NAPSI scores have been reported. The data
      further suggest that changes in NAPSI mirror changes in disease severity of other
      psoriatic manifestations, that is, in psoriatic arthritis and skin psoriasis. The
      effect only appears to be delayed due to the rate of growth of the nail plate.

PMID- 22859239
TI  - Ustekinumab improves health-related quality of life in Korean and Taiwanese
      patients with moderate to severe psoriasis: results from the PEARL trial.
AB  - BACKGROUND: The PEARL study showed that the proportion of psoriasis patients
      achieving the primary endpoint (at least 75% improvement from baseline to week 12
      in the Psoriasis Area and Severity Index) was significantly higher in ustekinumab
      treated patients compared with placebo. There is a paucity of data regarding the
      impact of psoriasis and its treatment on health-related quality of life (HRQoL)
      in Asian patients. OBJECTIVES: To evaluate the effect of ustekinumab on HRQoL in
      Korean/Taiwanese patients with moderate to severe psoriasis enrolled in the phase
      III, randomized, double-blind, placebo-controlled PEARL study. METHODS: In the
      PEARL study, 121 patients were randomized to receive ustekinumab 45 mg at weeks
      0, 4, and 16 (n=61) or placebo at weeks 0 and 4 with crossover to ustekinumab at
      weeks 12 and 16 (n=60). A major secondary endpoint was the change in Dermatology
      Life Quality Index (DLQI) from baseline at week 12. Other endpoints included the
      change in individual DLQI domains, proportion of patients achieving DLQI <= 1 (no
      negative effect), and proportion of patients achieving >= 5-point reduction in
      DLQI (clinically meaningful improvement) at week 12. RESULTS: At baseline,
      psoriasis had a very large effect on HRQoL (average DLQI, 15.7). At week 12,
      patients treated with ustekinumab 45 mg had significantly greater improvement
      from baseline in DLQI scores compared with placebo (mean decrease, 11.2 vs 0.5
      (P<0.001). Likewise, 32.2% and 1.7% of patients receiving ustekinumab 45 mg and
      placebo, respectively, achieved a DLQI <= 1, and 81.4% and 18.3% achieved >= 5
      point reduction (both P<0.001 vs placebo). Individual DLQI domains in the
      ustekinumab group were significantly improved compared with placebo (P<0.001).
      For ustekinumab-randomized patients, HRQoL improvements were sustained through
      week 28. Placebo patients who crossed over to ustekinumab experienced similar
      improvements compared with those randomized to ustekinumab. CONCLUSIONS:
      Ustekinumab significantly improves HRQoL in Korean/Taiwanese patients with
      moderate to severe psoriasis.

PMID- 22859240
TI  - Open label study to evaluate the efficacy of re-treatment with etanercept in
      patients with psoriasis.
AB  - BACKGROUND: Etanercept has been used to treat chronic plaque psoriasis.
      Previously reported data demonstrated that some patients experienced secondary
      failure and frequently rotational-switch therapy is used. The re-treatment with
      etanercept as part of the rotational therapy could be considered as another safe
      and efficient therapeutic approach. OBJECTIVE: To evaluate the efficacy of the re
      treatment with etanercept in patients with a history of etanercept use with good
      response and secondary loss of efficacy. METHODS: This is an open label
      prospective study involving 20 patients with moderate to severe plaque psoriasis,
      who had been initially treated with etanercept and were re-treated after a
      variable interval with 50 mg BIW for 12 weeks. RESULTS: At week 12 of etanercept
      re-treatment, 13 of 20 patients (65%) achieved a PGA score of 2 or less and 40%
      (8 of 20), achieved a PGA score of 0 to 1. Etanercept was well tolerated and no
      serious adverse events were reported. LIMITATIONS: Our study involved a small
      number of patients. Failure of etanercept was establish by patient's history.
      However we were able to correlate such failure from our medical records in 17
      patients. CONCLUSIONS: Re-treatment with etanercept, after secondary loss of
      efficacy should be considered in patients with psoriasis if satisfactory therapy
      cannot be achieved with other therapeutic regimens.

PMID- 22859241
TI  - Trends in older adult psoriasis outpatient health care practices in the United
      States.
AB  - BACKGROUND: Psoriasis is among the top dermatologic diagnoses for older adult
      patients, and the number of older adult psoriasis patients is expected to rise.
      PURPOSE: To characterize trends in older adult psoriasis health care practices of
      US ambulatory physician offices from 1993 to 2009. METHODS: We used data from the
      National Ambulatory Medical Care Survey to assess demographics, specialties seen,
      and treatment in visits by older adult patients, 55 years of age and older.
      RESULTS: There were approximately 14.1 million outpatient visits for psoriasis
      among the older adult population during the study period. Older adult psoriasis
      patients were 52.4% female and 47.6% male. The most frequent older adult age
      group seen for psoriasis was the 55 to 64 year age group. Dermatologists saw
      69.3% of patients, internists saw 14.5%, and general and family practitioners saw
      11.6%. Topical corticosteroids were the most frequently prescribed medications.
      Dermatologists preferred clobetasol whereas non-dermatologists more commonly
      prescribed betamethasone. For both the 18 to 54 year age group and the 55 and
      older group, the leading 7 out of 10 medications prescribed were topical
      corticosteroids and calcipotriene. However, etanercept, coal tar, and
      fluocinolone were among the leading medications in the younger group but not in
      the 55 and older group. CONCLUSIONS: Treatment approach for older adult psoriasis
      patients showed some differences among medical specialties and among the younger
      and older age groups. Further research specific to older adult psoriasis patients
      is needed to determine optimal treatment strategies for this patient population.

PMID- 22859242
TI  - Efficacy and tolerability of two commercial hyperpigmentation kits in the
      treatment of facial hyperpigmentation and photo-aging.
AB  - BACKGROUND: Hyperpigmentary disorders are common aesthetic skin conditions that
      can be very concerning to patients and both challenging and time-consuming for
      the physician to treat. Several companies commercialize hyperpigmentation kits
      for the lightening of dark spots and improvement of overall skin dyschromia.
      Unfortunately, clinical data from controlled studies to support the efficacy and
      tolerability of these kits are typically lacking. OBJECTIVE: This investigator
      blinded, randomized trial was undertaken to compare two commercial
      hyperpigmentation systems (kits) used for the treatment of facial
      hyperpigmentation and photo-aging. METHODS: Female subjects with at least mild
      facial hyperpigmentation and photo-aging were randomized to treatment with either
      the four product SkinMedica (SKM) regimen or the 7-product Obagi (OMP) regimen.
      Evaluations were conducted at baseline, 4, 8, and 12 weeks. Subjects were
      evaluated by the blinded investigator for clinical efficacy and tolerability
      using grading scales. Standardized digital photographs were taken at baseline and
      week 12. Self-assessment questionnaires were completed at week 12. Thirty-five
      females (SKM=17, OMP=18) completed the 12-week study. RESULTS: Both treatment
      regimens showed a significant improvement at week 12 (compared to baseline) for
      Overall Hyperpigmentation, Global Photo-aging and Sallowness. At week 12, there
      was no significant difference between treatment groups in Global Response to
      Treatment. Tolerability was good for both regimens based on investigator
      assessments. Subject self-assessments showed no consistent differences in
      efficacy between the two regimens. Similarly, there was no significant difference
      in subject satisfaction or intent to continue use between the two regimens.
      CONCLUSION: This clinical study demonstrated that both systems were equally
      effective at reducing hyperpigmentation and global photo-aging in females with
      mottled pigmentation and photodamaged facial skin.

PMID- 22859244
TI  - The use of cyclosporine in dermatology.
AB  - Cyclosporine is an immunosuppressive drug that acts selectively on T-cells by
      inhibiting calcineurin phosphorylase. It has been used in dermatology since its
      approval for US Food and Drug Administration in 1997 for the use in psoriasis.
      While indicated only for the treatment of moderate to severe psoriasis,
      cyclosporine has also been used as an off-label drug for the treatment of various
      inflammatory skin conditions, including atopic dermatitis, blistering disorders,
      and connective tissue diseases. In this article, we review the use of
      cyclosporine in dermatology.

PMID- 22859243
TI  - Treatment with a novel topical nanoemulsion (NB-001) speeds time to healing of
      recurrent cold sores.
AB  - BACKGROUND: Current topical therapies for cold sores are only marginally
      beneficial due to poor skin penetration. We assessed the safety and efficacy of a
      novel topical antiviral nanoemulsion (NB-001) with high tissue bioavailability.
      OBJECTIVES: The primary endpoint was the time to lesion healing. METHODS: 482
      subjects with recurrent cold sores were randomized to self-initiate treatment
      with either vehicle or NB-001 (0.1%, 0.3% or 0.5%) at the first signs or symptoms
      of a cold sore episode. Lotion was applied 5 times per day, approximately 3 to 4
      hours apart, for 4 days. Time to lesion healing was correlated with NB-001
      bioavailability determined in human cadaver skin. RESULTS: Subjects treated with
      0.3% NB-001 showed a 1.3-day improvement in the mean time to healing compared to
      vehicle (P=0.006). This was consistent with human cadaver skin data indicating
      that the 0.3% nanoemulsion had the highest bioavailability, compared to 0.1% and
      0.5% emulsions. No significant safety or dermal irritation concerns or systemic
      absorption were noted with any of the doses. CONCLUSIONS: Topical NB-001 (0.3%)
      was well tolerated and highly efficacious in shortening the time to healing of
      cold sores. The improvement in time to healing was similar to that reported for
      oral nucleoside analogues, but without systemic exposure. Topical agents for
      recurrent herpes labialis (cold sores) reduce healing time by one half day,
      compared to oral therapies that speed healing by a day or more. A topical
      antiviral nanoemulsion was well tolerated and improved cold sore healing time by
      over a day compared to vehicle control. Nanoemulsion (NB-001) could represent a
      more efficacious topical treatment for recurrent cold sores.

PMID- 22859245
TI  - Reconstruction of a lower eyelid defect with a V to Y island flap.
AB  - Repair of full thickness defects in the lower eyelid following extirpation of
      malignant tumors presents a challenge to the reconstructive surgeon. There are
      several techniques to choose from, depending on the defect's size and location.

PMID- 22859247
TI  - Treatment of psoriasis and long-term maintenance using 308 nm excimer laser,
      clobetasol spray, and calcitriol ointment: a case series.
AB  - Psoriasis is a chronic inflammatory skin disease that is characterized by
      thickened red plaques covered with silvery scales. Excimer laser therapy is a
      cutting-edge advancement in UVB phototherapy. In contrast to traditional
      phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it
      spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of
      UVB irradiation. Targeted UVB therapy is a possible treatment especially for many
      who have failed topical treatments, systemic therapy, and traditional
      phototherapy. For safe and effective psoriasis treatment, a combination of
      therapies may be used, including a combination of laser treatment with topical
      medications. We present two cases demonstrating effective treatment with excimer
      laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks.
      Long-term near-clearance of psoriasis was sustained after 6 months and one-year
      follow up periods without further therapy.

PMID- 22859249
TI  - Ustekinumab for treatment of plaque psoriasis in a patient with Down syndrome.
AB  - Down syndrome (DS) is the most common chromosomal disorder and a major cause of
      mental retardation. Down syndrome phenotype is complex and may present a
      combination of dysmorphic features, congenital heart disease and immunological
      deficiency. Psoriasis it has been noted to be 0.5%-8% in patients with DS and
      numerous factors can limit the use of therapeutic options, in particular long
      term organ-specific toxicity, and the risk of opportunistic infections. It is
      still debated whether the use of biologics in the treatment of DS-related
      psoriasis is safe. We have valuated the efficacy and safety of ustekinumab
      treatment in-patient with DS suffering from plaque type psoriasis. A 31-year-old
      patient suffering from plaque type psoriasis since the age of 14, showed a PASI
      score of 12 after the failure of anti-TNF agents. We switched the patient to
      ustekinumab treatment at the standard dose of 45 mg subcutaneously initially and
      4 weeks later, followed by 45 mg every 12 weeks. The patient showed a significant
      improvement of the PASI score already after 4 weeks of treatment and further
      improvements were observed throughout the treatment. We report the first case of
      DS-correlated psoriasis patient treated for a long-term period with various
      biologics, showing a satisfactory safety profile undergoing treatment. In our
      experience, ustekinumab has demonstrated a high efficacy, relatively rapid onset
      of action, favorable safety profile, and can be considered a good treatment
      option even after failure to respond to other biologic therapies in patient with
      DS.

PMID- 22859250
TI  - Case report: Vogt-Koyanagi-Harada disease in an African-American female.

PMID- 22859251
TI  - Chronic ulcers: when to consider malignancy?

PMID- 22859254
TI  - Creatinine-based vancomycin dosing regimens in neonates: there is more to
      consider than the variation in drug assay.

PMID- 22859255
TI  - Left ventricle-right atrium communication along with a membranous septum
      aneurysm.

PMID- 22859256
TI  - Demonstration of a rare variant of partial anomalous pulmonary venous drainage
      and quantification of shunt by cardiac magnetic resonance.

PMID- 22859257
TI  - Pathways for C-H bond cleavage of propane sigma-complexes on PdO(101).
AB  - We used dispersion-corrected density functional theory (DFT-D3) calculations to
      investigate the initial C-H bond cleavage of propane sigma-complexes adsorbed on
      the PdO(101) surface. The calculations predict that propane molecules adsorbed in
      eta(1) configurations can undergo facile C-H bond cleavage on PdO(101), where the
      energy barrier for C-H bond activation is lower than that for desorption for each
      molecular complex. The preferred pathway for propane dissociation on PdO(101)
      corresponds to cleavage of a primary C-H bond of a so-called staggered p-2eta(1)
      complex which initially coordinates with the surface by forming two H-Pd dative
      bonds, one at each CH(3) group. Among all of the adsorbed propane complexes, the
      staggered p-2eta(1) complex has the highest binding energy and must overcome the
      lowest energy barrier for C-H bond scission. Analysis of the atomic charges
      reveals that propane C-H bond cleavage occurs heterolytically on PdO(101), and
      suggests that primary C-H bond activation is favored because a more stabilizing
      charge distribution develops within the 1-propyl transition state structures.
      Lastly, we conducted kinetic simulations using microkinetic models derived from
      the DFT-D3 structures, and find that the models reproduce the apparent activation
      energy for propane dissociation on PdO(101) to within 14% of that determined
      experimentally. We show that the entropic contributions of the adsorbed
      transition structures greatly exceed those predicted by the harmonic oscillator
      model, and that quantitative agreement with the apparent dissociation pre-factor
      may be obtained by approximating two of the frustrated adsorbate motions as free
      motions while treating the remaining modes as harmonic vibrations.

PMID- 22859258
TI  - Induction of apoptosis by laminarin, regulating the insulin-like growth factor-IR
      signaling pathways in HT-29 human colon cells.
AB  - In recent years, algae have been highlighted as potential sources of anticancer
      agents. Laminarin is a molecule found in marine brown algae that has potentially
      beneficial biological activities. However, these activities have not been
      investigated. In the present study, we examined the effects of laminarin on HT-29
      cells and analyzed its effect on the insulin-like growth factor (IGF-IR)
      signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assays revealed that laminarin induced cell
      death in a dose-dependent manner. Western blotting showed that laminarin
      decreased mitogen-activated protein kinases (MAPK) and ERK phosphorylation.
      Decreased proliferation depended on IGF-IR, which was associated with the
      downregulation of MAPK/ERK. These results are important for understanding the
      roles of IGF-IR in colon cancer cell tumorigenesis, and suggest that laminarin
      shows activity against human colon cancer.

PMID- 22859259
TI  - Resect and discard strategy in clinical practice: a prospective cohort study.
AB  - BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has shown promising results
      in discriminating adenomatous from non-adenomatous colonic polyps. In patients
      with small polyps (< 10  mm), the application of NBI within a "resect and
      discard" strategy, might allow post-polypectomy surveillance intervals to be
      determined independently from histopathology. The aim of the present study was to
      assess the feasibility and safety of this approach in routine clinical practice.
      PATIENTS AND METHODS: Consecutive colonoscopy outpatients with one or more polyps
      smaller than 10  mm were prospectively included. Each polyp was categorized by
      the endoscopist as adenoma or non-adenoma according to simplified NBI criteria,
      and future post-polypectomy surveillance interval was assigned accordingly.
      Following histopathology, post-polypectomy surveillance interval was subsequently
      re-assigned, and the accordance between endoscopy- and histology-directed
      surveillance strategies was calculated. RESULTS: Among 942 colonoscopy patients,
      286 (30.4 %) with only small polyps were included. In total, 511 small polyps
      were evaluated; 350 (68.5 %) were adenomas and 18 of these (5.1 %) had histologic
      features of advanced neoplasia. For the in vivo diagnosis of adenoma, NBI
      sensitivity, specificity, accuracy, and positive and negative likelihood ratios
      were 94.9 %, 65.8 %, 85.7 %, 2.80, and 0.08, respectively. The endoscopy-directed
      surveillance strategy was in accordance with the histology-directed strategy in
      237 of 286 patients (82.9 %). In 9.8 % and 7.3 % patients, the endoscopy-directed
      approach would have resulted in early and delayed surveillance, respectively.
      CONCLUSIONS: The resect and discard strategy seems to be a viable, safe, and cost
      effective approach for the management of patients with small polyps. However,
      caution in the application of the strategy should be advocated for patients with
      polyps 6 - 9  mm in size and those with right-sided lesions, due to their
      malignant potential. The study was registered on Clinicaltrials.gov
      (NCT01462123).

PMID- 22859260
TI  - Luminescence properties of Tb3+-doped CaMoO4 nanoparticles: annealing effect,
      polar medium dispersible, polymer film and core-shell formation.
AB  - Tb(3+)-doped CaMoO(4) (Tb(3+) = 1, 3, 5, 7, 10, 15 and 20 atom%) core and core
      shell nanoparticles have been prepared by urea hydrolysis in ethylene glycol (EG)
      as capping agent as well as reaction medium at low temperature ~150  degrees C.
      As-prepared samples were annealed at 500 and 900  degrees C for 4 h to eliminate
      unwanted hydrocarbons and/or H(2)O present in the sample and to improve
      crystallinity. The synthesised nanophosphors show tetragonal phase structure. The
      crystallite size of as-prepared sample is found to be ~18 nm. The luminescence
      intensity of the (5)D(4) -> (7)F(5) transition at 547 nm of Tb(3+) is much higher
      than that of the (5)D(4) -> (7)F(6) transition at 492 nm. 900  degrees C annealed
      samples show the highest luminescence intensity. The intensity ratio R (I[(5)D(4)
      -> (7)F(6)]/I[(5)D(4) -> (7)F(5)]) lies between 0.3-0.6 for as-prepared, 500 and
      900  degrees C annealed samples. The luminescence decay of (5)D(4) level under
      355 nm excitation shows biexponential behaviour indicating availability of Tb(3+)
      ions on surface and core regions of particle; whereas, contribution of Mo-O
      charge transfer to lifetime is obtained under 250 nm excitation. The CIE
      coordinates of as-prepared, 500 and 900  degrees C annealed 5 atom% Tb(3+)-doped
      CaMoO(4) samples under 250 nm excitation are (0.28, 0.32), (0.22, 0.28) and
      (0.25, 0.52), respectively. The dispersed particles in polar medium and its
      polymer film show green light emission. The luminescence intensity is improved
      significantly after core-shell formation due to extent of decrease of non
      radiative rates arising from surface dangling bonds and capping agent. Quantum
      yields of as-prepared samples of 1, 5 and 7 atom% Tb(3+)-doped CaMoO(4) samples
      are found to be 10, 3 and 2, respectively.

PMID- 22859261
TI  - Highly modular access to functionalised metal-carbenes via post-modifications of
      a single bromoalkyl-substituted NHC-Pd(II) complex.
AB  - The synthesis of a bromopropyl-substituted NHC-Pd(II) complex, which can undergo
      exemplary and versatile 2nd and 3rd generation post-modifications easily
      affording 7 new functionalised NHC complexes, is demonstrated.

PMID- 22859262
TI  - Differential Tus-Ter binding and lock formation: implications for DNA replication
      termination in Escherichia coli.
AB  - In E. coli, DNA replication termination occurs at Ter sites and is mediated by
      Tus. Two clusters of five Ter sites are located on each side of the terminus
      region and constrain replication forks in a polar manner. The polarity is due to
      the formation of the Tus-Ter-lock intermediate. Recently, it has been shown that
      DnaB helicase which unwinds DNA at the replication fork is preferentially stopped
      at the non-permissive face of a Tus-Ter complex without formation of the Tus-Ter
      lock and that fork pausing efficiency is sequence dependent, raising two
      essential questions: Does the affinity of Tus for the different Ter sites
      correlate with fork pausing efficiency? Is formation of the Tus-Ter-lock the key
      factor in fork pausing? The combined use of surface plasmon resonance and GFP
      Basta showed that Tus binds strongly to TerA-E and G, moderately to TerH-J and
      weakly to TerF. Out of these ten Ter sites only two, TerF and H, were not able to
      form significant Tus-Ter-locks. Finally, Tus's resistance to dissociation from
      Ter sites and the strength of the Tus-Ter-locks correlate with the differences in
      fork pausing efficiency observed for the different Ter sites by Duggin and Bell
      (2009).

PMID- 22859263
TI  - Ptaquiloside-induced early-stage urothelial lesions show increased cell
      proliferation and intact beta-catenin and E-cadherin expression.
AB  - Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin,
      ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside
      contaminates underground waters as well as meat and milk from bracken-grazing
      animals and is a suspected human carcinogen. A better understanding of the
      underlying mechanisms of carcinogenesis can be achieved by studying the early
      stages of this process. Unfortunately, most research on ptaquiloside has focused
      on the late, malignant, lesions, so the early changes of ptaquiloside-induced
      carcinogenesis remain largely unknown. This study aims to characterize early
      stage ptaquiloside-induced urinary bladder lesions both morphologically and
      immunohistochemically. 12 male CD-1 mice were administered 0.5 mg ptaquiloside
      intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment.
      12 control animals were administered saline. Bladders were tested
      immunohistochemically for antibodies against a cell proliferation marker (Ki-67),
      and two cell adhesion markers (E-cadherin and beta-catenin). Two exposed animals
      died during the work. Six ptaquiloside-exposed mice developed low-grade and two
      developed high grade urothelial dysplasia. No lesions were detected on control
      animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on
      dysplastic urothelium from ptaquiloside-exposed mice, compared with controls. No
      differences were found concerning E-cadherin and beta-catenin expression. Early
      stage ptaquiloside-induced urothelial lesions show increased cell proliferation
      but there is no evidence for reduced intercellular adhesiveness, though this may
      be a later event in tumor progression.

PMID- 22859264
TI  - Are new antithrombotics the modern fountain of youth? Achievements and
      limitations.

PMID- 22859266
TI  - Carbon dioxide as a carbon source in organic transformation: carbon-carbon bond
      forming reactions by transition-metal catalysts.
AB  - Recent carbon-carbon bond forming reactions of carbon dioxide with alkenes,
      alkynes, dienes, aryl zinc compounds, aryl boronic esters, aryl halides, and
      arenes having acidic C-H bonds are reviewed in which transition-metal catalysts
      play an important role.

PMID- 22859265
TI  - Atopaxar. A novel player in antiplatelet therapy?
AB  - Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor
      1 (PAR-1) thrombin receptor antagonist. To date, Atopaxar has been investigated
      in phase II trials with focus on safety and tolerability in patients with acute
      coronary syndromes or stable coronary artery disease on top of standard
      antiplatelet therapy. Atopaxar was generally well tolerated, however a rise in
      liver enzymes and prolongation of the QTcF interval were observed. The data
      suggest, that atopaxar administration may promote some minor bleeding
      complications, but does not seem to significantly increase the risk of major
      bleeding. Although not powered for efficacy, the currently available data suggest
      potential benefits in patients at high risk for recurrent ischemic events on top
      of standard antiplatelet therapy. In conclusion, more studies (e.g. phase III)
      are needed to evaluate efficacy and safety of atopaxar.

PMID- 22859267
TI  - A layered zinc phosphate decorated with organic fluorophores for selective
      luminescent sensing of metal cations.
AB  - A new type of metal-phosphate-base cation sensor is constructed via attaching
      organic TPT fluorophores to the framework of the porous inorganic layers. It
      shows excellent sensitivity and selectivity for a series of cations.

PMID- 22859268
TI  - Combining estimates from two surveys: an example from monitoring 2009 influenza A
      (H1N1) pandemic vaccination.
AB  - During the 2009 influenza A (H1N1) pandemic, there was an ongoing need to monitor
      2009 H1N1 vaccination coverage at the national and state level to evaluate the
      vaccination campaign; thus, precise vaccination coverage estimates were needed in
      a timely fashion. The current objective is to describe and evaluate the
      methodology used to combine 2009 H1N1 vaccination coverage estimates from the
      Behavioral Risk Factor Surveillance System (BRFSS) and the National 2009 H1N1 Flu
      Survey (NHFS). H1N1 state level vaccination coverage estimates were combined by
      taking weighted averages of the BRFSS and NHFS estimates, with more weight given
      to the estimate with the larger effective sample size (sample size/design
      effect). The impact of the choice of weights was evaluated by comparing estimates
      when the design effect was removed from the weights. Combined vaccination
      coverage estimates for children generally fell midway between NHFS and BRFSS
      estimates because of larger NHFS sample sizes but smaller BRFSS design effects.
      Adult estimates were more closely weighted to BRFSS estimates because of larger
      BRFSS sample sizes. Combined standard errors were smaller than the survey
      specific standard errors. When removing the design effect from the weights, the
      child combined estimates were more closely weighted to those from NHFS, resulting
      in larger standard errors. Adult combined estimates were similar regardless of
      choice of weight because of similar design effects across the two surveys.
      Combining estimates by weighting by the effective sample size allowed timely
      release of more precise estimates in all states during the 2009 H1N1 pandemic.

PMID- 22859269
TI  - Prevention of tobacco carcinogen-induced lung cancer in female mice using
      antiestrogens.
AB  - Increasing evidence shows that estrogens are involved in lung cancer
      proliferation and progression, and most human lung tumors express estrogen
      receptor beta (ERbeta) as well as aromatase. To determine if the aromatase
      inhibitor anastrozole prevents development of lung tumors induced by a tobacco
      carcinogen, alone or in combination with the ER antagonist fulvestrant,
      ovariectomized female mice received treatments with the tobacco carcinogen 4
      (methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) along with daily supplements
      of androstenedione, the substrate for aromatase. Placebo, anastrozole and/or
      fulvestrant were administered in both an initiation and a promotion protocol of
      lung tumorigenesis. The combination of fulvestrant and anastrozole given during
      NNK exposure resulted in significantly fewer NNK-induced lung tumors (mean = 0.5)
      compared with placebo (mean = 4.6, P < 0.001), fulvestrant alone (mean = 3.4, P <
      0.001) or anastrozole alone (mean = 2.8, P = 0.002). A significantly lower Ki67
      cell proliferation index was also observed compared with single agent and control
      treatment groups. Beginning antiestrogen treatment after NNK exposure, when
      preneoplastic lesions had already formed, also yielded maximum antitumor effects
      with the combination. Aromatase expression was found mainly in macrophages
      infiltrating preneoplastic and tumorous areas of the lungs, whereas ERbeta was
      found in both macrophages and tumor cells. Antiestrogens, especially in
      combination, effectively inhibited tobacco carcinogen-induced murine lung
      tumorigenesis and may have application for lung cancer prevention. An important
      source of estrogen synthesis may be inflammatory cells that infiltrate the lungs
      in response to carcinogens, beginning early in the carcinogenesis process. ERbeta
      expressed by inflammatory and neoplastic epithelial cells in the lung may signal
      in response to local estrogen production.

PMID- 22859270
TI  - MiR-196a binding-site SNP regulates RAP1A expression contributing to esophageal
      squamous cell carcinoma risk and metastasis.
AB  - Polymorphisms in 3' untranslated region (UTR) of cancer-related genes might
      affect regulation by microRNA (miRNA) and contribute to carcinogenesis. In this
      study, we screened several single nucleotide polymorphisms (SNPs) in 3'UTR of
      cancer-related genes and investigated their effects on the risk of esophageal
      squamous cell carcinoma (ESCC). First, we used SNaPshot assay to genotype seven
      3'UTR SNPs in 537 ESCC cases and 608 normal controls in a Chinese Han population
      and found that SNP rs6573 in 3'UTR of RAS-related proteins (RAP1A) was
      significantly associated with ESCC risk [P = 0.02, odds ratio (OR) = 0.43; 95%
      confidence interval (CI): 0.21-0.91] and pathologic stage (P = 0.03, OR = 1.89;
      95% CI: 1.06-3.36). A putative binding site for miRNA-196a (miR-196a) exists in
      the 3'UTR of RAP1A, and the genetic variant, rs6573 A->C, is present in this
      binding region. We confirmed that miR-196a regulated the expression of RAP1A by
      luciferase reporter assay and that the regulation was affected by the RAP1A
      genotype. SNP rs6573 A to C change interfere in the interaction of miR-196a
      binding to RAP1A 3'UTR, resulting in higher constitutive expression of RAP1A.
      Moreover, we observed that RAP1A was overexpressed in the majority of ESCC
      tissues and correlated with RAP1A genotype and lymph node metastasis. In vitro
      study indicated RAP1A might function as a promoter for esophageal cancer cell
      migration and invasion through matrix metalloproteinase 2. Our study highlights
      RAP1A and SNP rs6573 functioning as potential personal diagnostic and prognosis
      markers for ESCC.

PMID- 22859271
TI  - Functional invadopodia formation through stabilization of the PDPN transcript by
      IMP-3 and cancer-stromal crosstalk for PDPN expression.
AB  - We previously reported that insulin-like growth factor-II mRNA-binding protein-3
      (IMP-3) depletion (IMP-3(Delta)) was shown to inhibit invadopodia formation and
      extracellular matrix degradation capacity in oral squamous cell carcinoma (OSCC)
      cells. In this study, we found that IMP-3(Delta) cells significantly
      downregulated the podoplanin (PDPN) level, which resulted in a loss of
      extracellular matrix degradation activity, although invadopodia was still
      thriving. From RNA in situ hybridization using a digoxigenin-labeled 3'UTR
      recognition probe of PDPN and reporter assay with 3'UTR of the PDPN gene cloned
      downstream from the luciferase reporter gene, we revealed that IMP-3 depletion
      was shown to be downregulated, which most probably lowered PDPN gene expression
      by reducing mRNA stabilization. In a xenograft model, PDPN depletion was the
      cause of a decrease in tumor volume and regional infiltration into nearby stroma.
      Taken together, transforming growth factor beta 1 increased PDPN expression,
      which potentiated cancer invasion through increased invadopodia formation and
      extracellular matrix degradation in the low invasive OSCC cell line.
      Reciprocally, interleukin-1 beta secreted by OSCC cells, stimulated transforming
      growth factor beta 1 secretion from stromal fibroblasts to induce PDPN expression
      in OSCC cells. In addition, a retrospective investigation of OSCC patients found
      that IMP-3 and PDPN expression significantly correlated with lymph node
      metastasis of OSCC patients. Moreover, co-expression of IMP-3 and PDPN were
      frequently detected both in primary and lymph nodes metastatic OSCC cells using
      immunohistochemical dual staining. Thus, the IMP-3-PDPN axis may be a sensitive
      target molecule in anti-invadopodia therapy for the treatment of metastatic
      cancers.

PMID- 22859272
TI  - Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109
      cells.
AB  - Apoptosis plays a critical role in the development and homeostasis of
      multicellular organisms, and endoplasmic reticulum stress (ERS) is one of the
      intrinsic apoptosis pathways. Previous studies have shown that adenosine induces
      apoptosis in several cancer cell lines. However, the molecular mechanism remains
      poorly understood. In this study, we explored whether adenosine triggers
      apoptosis of EC109 esophageal carcinoma (EC) cells by ERS. The MTT assay was used
      to determine cell proliferation; cell cycle detection (FCM) and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were
      performed to determine cell apoptosis. The subcellular distribution and
      expression of the ERS-related proteins GRP78, cleaved caspase-3, cleaved caspase
      4, CHOP and NF-kappaB p65 were detected by western blot techniques. NF-kappaB
      activation was measured by electrophoretic mobility shift assay (EMSA). The MTT
      assay demonstrated that adenosine inhibited EC109 cell proliferation in a dose-
      and time-dependent manner. FCM and TUNEL assay verified that adenosine caused an
      apoptotic peak in cell cycle arrest and a higher percentage of apoptotic cells.
      Western blot analysis confirmed that the expression of GRP78, cleaved caspase-4,
      CHOP, NF-kappaB p65 and cleaved caspase-3 were upregulated in a dose-dependent
      manner after adenosine treatment. EMSA revealed that adenosine activated NF
      kappaB p65. This is the first demonstration that adenosine inhibits cell
      proliferation, increases GRP78 and NF-kappaB p65 expression and induces apoptosis
      by CHOP and caspase-4 pathways. The ERS pathway is involved in adenosine-induced
      apoptosis in EC109 cells.

PMID- 22859273
TI  - X-ray reduction correlates with soaking accessibility as judged from four non
      crystallographically related diiron sites.
AB  - X-ray crystallography is extensively used to determine the atomic structure of
      proteins and their cofactors. Though a commonly overlooked problem, it has been
      shown that structural damage to a redox active metal site may precede loss of
      diffractivity by more than an order of magnitude in X-ray dose. Therefore the
      risk of misassigning redox states is great. Adequate treatment and consideration
      of this issue is of paramount importance in metalloprotein science, from
      experimental design to interpretation of the data and results. Some metal sites
      appear to be much more amenable to reduction than others, but the underlying
      processes are poorly understood. Here, we have analyzed the four non
      crystallographically related diiron sites in a crystal of the ribonucleotide
      reductase R2F protein from Corynebacterium ammoniagenes. We conclude that the
      amount of X-ray reduction a metal site suffers correlates with its soaking
      accessibility. This direct observation supports the hypothesis that a diffusion
      component is involved in the X-ray reduction process.

PMID- 22859274
TI  - Construction of quantitative molecular isotherms from FTIR analysis of dinitrogen
      (N2) adsorption on a microporous NaY zeolite.
AB  - We focus on the analysis of N(2) adsorption on NaY faujasite investigated by
      means of both the FTIR and volumetric measurements. We examine how these two
      approaches, when combined, can lead to a more advanced quantitative description
      featuring the understanding of gas adsorption both at the molecular and the
      macroscopic scales. For this task, we describe hereafter the method used and how
      we circumvented drawbacks encountered along the way. Finally we share new insight
      obtained by working step by step towards the construction of the first
      quantitative molecular isotherms of N(2) on a NaY zeolite.

PMID- 22859275
TI  - Diffusion tensor analysis of pediatric multiple sclerosis and clinically isolated
      syndromes.
AB  - BACKGROUND AND PURPOSE: DTI has shown focal and diffuse white matter
      abnormalities in adults and children with MS. Here we explore whether DTI
      abnormalities are present at the time of a first attack or CIS in children and
      whether early DTI features can predict the development of MS. MATERIALS AND
      METHODS: We assessed region-of-interest and tract-based mean ADC and mean FA
      values for 3 major white matter pathways and NAWM in 20 children with MS, 27
      children with forms of CIS, and controls. Tracts were selected by using standard
      region-of-interest placements on color FA maps. Identical ROIs were placed in the
      NAWM on b = 0 T2-weighted images to ensure that both ROIs and resulting tracts
      passed through NAWM. Conventional MR imaging characteristics were assessed by
      visual inspection. Statistical analysis compared FA and ADC values between groups
      by a t test. Logistic regression assessed the predictive value of DTI measures
      and published conventional MR imaging measures for conversion from CIS to MS.
      RESULTS: In pediatric patients with MS, all white matter pathways and analysis
      confined to the NAWM demonstrated higher mean ADC values and lower mean FA than
      in controls. In contrast, there were no significant differences in mean ADC and
      mean FA of white matter pathways in all CIS cohorts compared with controls. In
      the CIS cohort, none of the DTI measures in white matter pathways or in NAWM were
      significantly associated with conversion to RRMS in univariate or multivariate
      models (P > .05 in all models). CONCLUSIONS: There are significant anisotropic
      abnormalities in the NAWM of major tracts in children with MS. In contrast, there
      were no significant changes in pediatric patients with CIS compared with controls
      at baseline. DTI measures did not predict conversion to MS. The period between
      CIS and conversion to pediatric MS may represent a window of opportunity for the
      prevention of diffuse damage in the CNS and potentially progressive disability.

PMID- 22859276
TI  - Diffusion MRI findings in monochorionic twin pregnancies after intrauterine fetal
      death.
AB  - BACKGROUND AND PURPOSE: Monochorionic twin pregnancies complicated by the IUFD of
      1 twin are associated with substantial morbidity to the survivor twin. The aim of
      this study was to determine whether fetal sonography, T2 MR imaging, and DWI can
      diagnose acute cerebral lesions in the survivor of an MC twin pregnancy shortly
      after fetal death of the co-twin. MATERIALS AND METHODS: During the study period
      (2007-2010) 34 cases of single IUFD were evaluated. Group A included 6 cases
      complicated by spontaneous IUFD. Group B had 10 cases of fetal death shortly
      after treatment of severe TTTS. These were compared with group C, with 18
      pregnancies treated by selective termination due to severe complications in MC
      pregnancies. RESULTS: Altogether 9/34 patients had abnormal prenatal cerebral
      findings. In group A, in 2/6 of pregnancies with spontaneous death, MR imaging
      showed findings of severe cerebral infarct, while cerebral damage was not evident
      by sonography. In another case, the surviving fetus was found to be hydropic on
      sonography, while MR imaging findings were normal. In group B, in 1/10 cases,
      cerebral infarct was demonstrated only by DWI. In 2 other cases, sonographic
      findings were normal, but MR imaging showed germinal matrix bleeding. In group C,
      in 1/18 cases, only DWI showed bilateral cerebral ischemia. In 2 other cases, MR
      imaging findings suggested germinal matrix bleeding and focal changes in the
      basal ganglia. In both cases, fetal sonographic findings were normal.
      CONCLUSIONS: In our study, early manifestations of cerebral ischemia in
      monochorionic twin pregnancies were better diagnosed with MR imaging, especially
      with DWI.

PMID- 22859277
TI  - Reduced regional gray matter volume in patients with chronic obstructive
      pulmonary disease: a voxel-based morphometry study.
AB  - BACKGROUND AND PURPOSE: Decreased oxygen supply may cause neuronal damage in the
      brains of patients with COPD, which is manifested by clinical symptoms such as
      neuropsychological deficits and mood disorders. The aim of the present study was
      to investigate brain gray matter change in COPD. MATERIALS AND METHODS: Using
      voxel-based morphometry based on the high-resolution 3D T1-weighted MR images of
      GM volume, we investigated 25 stable patients with COPD and 25 matching healthy
      volunteers. A battery of neuropsychological tests was also performed. RESULTS:
      Patients with COPD (versus controls) showed reduced GM volume in the frontal
      cortex (bilateral gyrus rectus, bilateral orbital and inferior triangular gyri,
      and left medial superior gyrus), right anterior insula, cingulate cortex (left
      anterior and middle gyri, right middle gyrus), right thalamus/pulvinar, right
      caudate, right putamen, right parahippocampus, and left amygdala. In COPD, in
      some of these regions, regional GM volume had positive correlations with arterial
      blood po(2), while in some regions, regional GM volume had negative correlations
      with disease duration. Patients with COPD (versus controls) had poorer
      performance in the Mini-Mental State Examination, Visual Reproduction, and Figure
      Memory tests. Moreover, the GM volume in the inferior triangular frontal cortex
      in patients with COPD was significantly correlated with the Picture Memory score.
      CONCLUSIONS: Our findings suggest GM reductions in a number of brain regions in
      COPD, which were associated with disease severity and may underlie the
      pathophysiologic and psychological changes in patients with COPD.

PMID- 22859278
TI  - Temperature-sensitive poly(N-isopropylacrylamide-co-butyl methylacrylate) nanogel
      as an embolic agent: distribution, durability of vascular occlusion, and
      inflammatory reactions in the renal artery of rabbits.
AB  - BACKGROUND AND PURPOSE: We have developed a new thermosensitive liquid embolic
      agent, PIB nanogel, that can be solidified at body temperature. We thus further
      investigated the distribution, durability of vascular occlusion, and inflammatory
      reactions of PIB in embolization of the renal artery of rabbits. MATERIALS AND
      METHODS: The bilateral renal arteries of 9 rabbits were first embolized with PIB
      at different injection rates. The distribution pattern of PIB was investigated by
      contact radiography and histology 1 hour after embolization. The right renal
      arteries of 20 rabbits were then embolized with PIB at the proper injection rate.
      Angiography and pathologic examination of the kidneys were performed at 1 week
      and 1, 2, and 3 months after embolization to evaluate the long-term outcomes.
      RESULTS: With the injection rate increasing, PIB could reach the more distal
      branch of the renal artery. The proper injection rate was chosen as 0.10 mL/s due
      to the homogeneous distribution of PIB from the main renal artery to the
      precapillary level at this rate. During a 3-month follow-up observation period,
      no angiographic recanalization was observed. Histologically, we found no
      disruption of the vessel wall or subintimal bleeding, no extravasation of PIB,
      and no evidence of neovascularization. Moreover, there was only a mild
      inflammatory response, manifested by few lymphocytic and monocellular
      infiltration, without foreign body granuloma formation. CONCLUSIONS: Embolization
      of the renal artery with PIB was easy and controllable, which could lead to a
      homogeneous and persistent occlusion without severe inflammatory changes. PIB
      might be a suitable material for intravascular embolization.

PMID- 22859279
TI  - Prospective comparison of angio-seal versus manual compression for hemostasis
      after neurointerventional procedures under systemic heparinization.
AB  - BACKGROUND AND PURPOSE: The use of arterial closure device in patients with
      prolonged high ACT values has not been extensively studied. The aim of this study
      was to compare the safety and efficacy of an arterial closure device, Angio-Seal,
      with manual compression in patients on anticoagulation following
      neurointerventional procedures. MATERIALS AND METHODS: This was a 2-center
      prospective study approved by our institutional review boards. In total, 153
      consecutive patients with 174 arteriotomies (86 men, 67 women; mean age, 56.1 +/-
      16.2 years) following femoral arterial puncture for neurointerventional
      procedures were enrolled in convenience sampling. All of the patients were
      systemically heparinized with an ACT between 250 and 500 seconds before removal
      of the sheath after the procedure. Group 1 consisted of 104 arteriotomies that
      were closed with an arterial closure device (Angio-Seal), and group 2 consisted
      of 70 arteriotomies treated with manual compression. The ACT before sheath
      removal, time to hemostasis, and complications immediately and 24 hours after the
      procedure were recorded. RESULTS: The mean ACT before sheath removal was 284.8 +/
      37.6 seconds (range, 250-414 seconds). The mean hemostasis time was
      significantly shorter in group 1 (2.4 +/- 11.7 minutes) compared with group 2
      (44.7 +/- 27.4 minutes) (95% CI, 38.16-51.24 minutes; P < .001). Hematoma
      occurred in 9 patients in group 1 (8.6%) and 18 in group 2 (25.7%). One patient
      developed an arterial occlusion after hemostasis with the closure device, but
      this was successfully revascularized. CONCLUSIONS: Angio-Seal was found to safely
      and effectively achieve rapid closure of the femoral access site in patients
      undergoing neuroendovascular procedures under systemic heparinization with an ACT
      in the range of 250-500 seconds.

PMID- 22859280
TI  - Intracranial atherosclerotic plaque enhancement in patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Inflammation of an atherosclerotic plaque is a well-known
      risk factor in the development of ischemic stroke and myocardial infarction. MR
      imaging is capable of characterizing inflammation by assessing plaque enhancement
      in both extracranial carotid arteries and coronary arteries. Our goal was to
      determine whether enhancing intracranial atherosclerotic plaque was present in
      the vessel supplying the territory of infarction by using high-resolution vessel
      wall MR imaging. MATERIALS AND METHODS: High-resolution vessel wall 3T MR imaging
      studies performed in 29 patients with ischemic stroke and intracranial vascular
      stenoses were reviewed for presence and strength of plaque enhancement. RESULTS:
      Sixteen patients were studied during the acute phase (<4 weeks from acute
      stroke), 5 patients in the subacute phase (4-12 weeks), and 8 patients in the
      chronic phase (>12 weeks) of the ischemic injury. In all of the acute phase
      patients, atherosclerotic plaque in the vessel supplying the stroke territory
      demonstrated strong enhancement. There was a trend of decreasing enhancement as
      the time of imaging relative to the ischemic event increased. CONCLUSIONS: Strong
      pathologic enhancement of intracranial atherosclerotic plaque was seen in all
      patients imaged within 4 weeks of ischemic stroke in the vessel supplying the
      stroke territory. The strength and presence of enhancement of the atherosclerotic
      plaque decreased with increasing time after the ischemic event. These findings
      suggest a relationship between enhancing intracranial atherosclerotic plaque and
      acute ischemic stroke.

PMID- 22859281
TI  - Head and neck tumors: assessment of perfusion-related parameters and diffusion
      coefficients based on the intravoxel incoherent motion model.
AB  - BACKGROUND AND PURPOSE: IVIM MR imaging provides perfusion and diffusion
      information with a single diffusion-weighted MR image. We determined whether PP
      and D differ among various types of head and neck tumors. MATERIALS AND METHODS:
      The study cohort included 123 head and neck tumors: 30 SCCs, 28 benign and 20
      malignant SG tumors, 36 lymphomas, and 9 schwannomas. The D and PP values were
      determined by using b-values of 0, 500, and 1000 s/mm(2) based on the IVIM model.
      RESULTS: The PP values (lymphomas, 0.09 +/- 0.04; SCCs, 0.15 +/- 0.04; and
      malignant SG tumors, 0.22 +/- 0.07) and D values (0.47 +/- 0.07 * 10(-3) mm(2)/s,
      0.82 +/- 0.17 * 10(-3) mm(2)/s, and 1.03 +/- 0.16 * 10(-3) mm(2)/s, respectively)
      were significantly different among the malignant tumors (P < .01). These values
      were also significantly different between pleomorphic adenomas (0.13 +/- 0.02 and
      1.44 +/- 0.39 * 10(-3) mm(2)/s) and Warthin tumors (0.19 +/- 0.04 and 0.73 +/-
      0.22 * 10(-3) mm(2)/s) (P < .001). The PP values of malignant SG tumors were
      significantly different from those of pleomorphic adenomas (P = .001) and the D
      values of the malignant SG tumors were significantly different from those of
      pleomorphic adenomas (P = .002) and Warthin tumors (P = .007). Schwannomas had
      large PP (0.23 +/- 0.08) and D values (1.26 +/- 0.20 * 10(-3) mm(2)/s), greatly
      overlapping those of some SG tumor types. CONCLUSIONS: Head and neck tumors had
      distinctive PP and D values by using IVIM MR imaging.

PMID- 22859282
TI  - Migration: a notable feature of cerebral sparganosis on follow-up MR imaging.
AB  - BACKGROUND AND PURPOSE: Cerebral sparganosis is a rare parasitic infection caused
      by sparganum, which can migrate in the brain. The purpose of this study was to
      demonstrate the migration of cerebral sparganosis and describe its patterns on MR
      imaging. MATERIALS AND METHODS: MR images of 14 patients with cerebral
      sparganosis treated from 2005 to 2011 were retrospectively reviewed. Diagnosis
      was made on the basis of a constellation of clinical history, laboratory tests,
      imaging findings, and histopathology. At least 3 MR imaging studies were
      performed for each patient during the follow-up period ranging from 12 to 38
      months. Time interval, sites, enhanced pattern, and presumed routes of migration
      were evaluated. RESULTS: Both the initial lesions and migrated ones exhibited the
      "tunnel" sign and multiloculated rim enhancement. Migration was detected between
      4 and 18 months after the baseline MR imaging in 14 lesions (in 14 patients),
      while 3 of 14 lesions showed a second migration between 22 and 38 months. Nearly
      all migrations were limited to the same hemisphere except for 2 contralateral
      migrations through the thalamus. Most of the migrations were in close proximity
      (within the same lobe, to the adjacent lobe, from the basal ganglia to the
      cortex, from the cerebellum to the pons and interthalamus) except 1 from the
      basal ganglia to the cerebellum. A signal change along the presumed route of
      migration was seen in 3 patients. CONCLUSIONS: Migration is a notable feature of
      cerebral sparganosis. Demonstration of migration on MR imaging could be a key
      diagnostic clue and beneficial for the treatment policy.

PMID- 22859283
TI  - Clinical risk factors and CT imaging features of carotid atherosclerotic plaques
      as predictors of new incident carotid ischemic stroke: a retrospective cohort
      study.
AB  - BACKGROUND AND PURPOSE: Parameters other than luminal narrowing are needed to
      predict the risk of stroke more reliably, particularly in patients with <70%
      stenosis. The goal of our study was to identify clinical risk factors and CT
      features of carotid atherosclerotic plaques, in a retrospective cohort of
      patients free of stroke at baseline, that are independent predictors of incident
      stroke on follow-up. MATERIALS AND METHODS: We identified a retrospective cohort
      of patients admitted to our emergency department with suspected stroke between
      2001-2007 who underwent a stroke work-up including a CTA of the carotid arteries
      that was subsequently negative for acute stroke. All patients also had to receive
      a follow-up brain study at least 2 weeks later. From a random sample, we reviewed
      charts and imaging studies of patients with subsequent new stroke on follow-up as
      well as those who remained stroke-free. All patients were classified either as
      "new carotid infarct patients" or "no-new carotid infarct patients" based on the
      Causative Classification for Stroke. Independently, the baseline CTA studies were
      processed using a custom, CT-based automated computer classifier algorithm that
      quantitatively assesses a set of carotid CT features (wall thickness, plaque
      ulcerations, fibrous cap thickness, lipid-rich necrotic core, and
      calcifications). Univariate and multivariate statistical analyses were used to
      identify any significant differences in CT features between the patient groups in
      the sample. Subsequent ROC analysis allowed comparison to the classic NASCET
      stenosis rule in identifying patients with incident stroke on follow-up. RESULTS:
      We identified a total of 315 patients without a new carotid stroke between
      baseline and follow-up, and 14 with a new carotid stroke between baseline and
      follow-up, creating the main comparison groups for the study. Statistical
      analysis showed age and use of antihypertensive drugs to be the most significant
      clinical variables, and maximal carotid wall thickness was the most relevant
      imaging variable. The use of age >= 75 years, antihypertensive medication use,
      and a maximal carotid wall thickness of at least 4 mm was able to successfully
      identify 10 of the 14 patients who developed a new incident infarct on follow-up.
      ROC analysis showed an area under the ROC curve of 0.706 for prediction of new
      stroke with this new model. CONCLUSIONS: Our new paradigm of using age >= 75
      years, history of hypertension, and carotid maximal wall thickness of >4 mm
      identified most of the patients with subsequent new carotid stroke in our study.
      It is simple and may help clinicians choose the patients at greatest risk of
      developing a carotid infarct, warranting validation with a prospective
      observational study.

PMID- 22859284
TI  - Canadian experience with the pipeline embolization device for repair of
      unruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Flow-diverting stents, such as the PED, have emerged as a
      novel means of treating complex intracranial aneurysms. This retrospective
      analysis of the initial Canadian experience provides insight into technical
      challenges, clinical and radiographic outcomes, and complication rates after the
      use of flow-diverting stents for unruptured aneurysms. MATERIALS AND METHODS:
      Cases were compiled from 7 Canadian centers between July 2008 and December 2010.
      Each center prospectively tracked their initial experience; these data were
      retrospectively updated and pooled for analysis. RESULTS: During the defined
      study period, 97 cases of unruptured aneurysm were treated with the PED, with
      successful stent deployment in 94 cases. The overall complete or near-complete
      occlusion rate was 83%, with a median follow-up at 1.25 years (range 0.25-2.5
      years). Progressive occlusion was witnessed over time, with complete or near
      complete occlusion in 65% of aneurysms followed through 6 months, and 90% of
      aneurysms followed through 1 year. Multivariate analysis found previous aneurysm
      treatment and female sex predictive of persistent aneurysm filling. Most patients
      were stable or improved (88%), with the most favorable outcomes observed in
      patients with cavernous carotid aneurysms. The overall mortality rate was 6%.
      Postprocedural aneurysm hemorrhage occurred in 3 patients (3%), while ipsilateral
      distal territory hemorrhage was observed in 4 patients (3.4%). CONCLUSIONS: Flow
      diverting stents represent an important tool in the treatment of complex
      intracranial aneurysms. The relative efficacy and morbidity of this treatment
      must be considered in the context of available alternate interventions.

PMID- 22859285
TI  - Effect of bifurcation angle configuration and ratio of daughter diameters on
      hemodynamics of bifurcation aneurysms.
AB  - BACKGROUND AND PURPOSE: EL associated with ruptured aneurysms is higher than that
      for unruptured aneurysms. In this study, the effect of arterial morphologic
      variation of bifurcation aneurysms on EL was investigated in idealized models of
      middle cerebral artery aneurysms. MATERIALS AND METHODS: Bifurcation angle
      configuration and DA ratio were evaluated in 6 idealized numeric models. Type A
      and B bifurcation models were defined with symmetric and asymmetric bifurcation
      angles of 136 degrees , and 57 degrees  and 79 degrees , respectively. Three
      models with DA ratios of 1, 1.3, and 2 were constructed for each type. EL was
      calculated as the energy difference between aneurysm inflow and outflow at the
      aneurysm neck. Three growth paths (R1, R2, and R3) were proposed. RESULTS: The
      highest EL and influx occurred in bifurcations with DA ratios of 1 for both types
      A and B. As the DA ratio increases, flow distribution between branches becomes
      more asymmetric, resulting in a reduction of EL and intra-aneurysmal flow. No
      strong relation was found between bifurcation angle configuration, inflow flux,
      and EL. EL decreased with an increase in the AR and DA ratio and increased with
      an increase in the AR and reduction of DA ratio. CONCLUSIONS: EL determined in
      idealized models is less dependent on bifurcation angle configuration than on DA
      ratio, and the stability of the aneurysm strongly depends on variation of the
      daughter artery morphology after aneurysm growth.

PMID- 22859286
TI  - Patient radiation dose management in the follow-up of potential skin injuries in
      neuroradiology.
AB  - BACKGROUND AND PURPOSE: Radiation exposure from neurointerventional procedures
      can be substantial, with risk of radiation injuries. We present the results of a
      follow-up program applied to potential skin injuries in interventional
      neuroradiology based on North American and European guidelines. MATERIALS AND
      METHODS: The following guidelines approved in 2009 by SIR and CIRSE have been
      used over the last 2 years to identify patients with potential skin injuries
      requiring clinical follow-up: peak skin dose >3 Gy, air kerma at the patient
      entrance reference point >5 Gy, kerma area product >500 Gy . cm(2), or
      fluoroscopy time >60 minutes. RESULTS: A total of 708 procedures (325 in 2009 and
      383 in 2010) were included in the study. After analyzing each dose report, 19
      patients (5.9%) were included in a follow-up program for potential skin injuries
      in 2009, while in 2010, after introducing several optimizing actions and refining
      the selection criteria, only 4 patients (1.0%) needed follow-up. Over the last 2
      years, only 3 patients required referral to a dermatology service. CONCLUSIONS:
      The application of the guidelines to patient radiation dose management helped
      standardize the selection criteria for including patients in the clinical follow
      up program of potential skin radiation injuries. The peak skin dose resulted in
      the most relevant parameter. The refinement of selection criteria and the
      introduction of a low-dose protocol in the x-ray system, combined with a training
      program focused on radiation protection, reduced the number of patients requiring
      clinical follow-up.

PMID- 22859287
TI  - Imaging brain oxygenation with MRI using blood oxygenation approaches: methods,
      validation, and clinical applications.
AB  - SUMMARY: In many pathophysiologic situations, including brain neoplasms,
      neurodegenerative disease, and chronic and acute ischemia, an imbalance exists
      between oxygen tissue consumption and delivery. Furthermore, oxygenation changes
      following a stress challenge, such as with carbogen gas or acetazolamide, can
      yield information about cerebrovascular reactivity. The unique sensitivity of the
      BOLD effect to the presence of deoxyhemoglobin has led to its widespread use in
      the field of cognitive neurosciences. However, the high spatial and temporal
      resolution afforded by BOLD imaging does not need to be limited to the study of
      healthy brains. While the complex relationship between the MR imaging signal and
      tissue oxygenation hinders a direct approach, many different methods have been
      developed during the past decade to obtain specific oxygenation measurements.
      These include qBOLD, phase- and susceptibility-based imaging, and intravascular
      T2-based approaches. The aim of this review is to give an overview of the
      theoretic basis of these methods as well as their application to measure
      oxygenation in both healthy subjects and those with disease.

PMID- 22859288
TI  - Spinal arteriovenous metameric syndrome: clinical manifestations and endovascular
      management.
AB  - BACKGROUND AND PURPOSE: SAMS is a rare form of SCAVM. We discuss the clinical
      presentation, endovascular management, and outcome of this disease in our series.
      MATERIALS AND METHODS: Retrospective review was performed in patients with SCAVM
      and SAMS who underwent angiography with intent to treat at our institution from
      1980 to 2010. RESULTS: One hundred forty-eight SCAVMs were identified, and 28
      (19%) of these were SAMS. Of these 28 patients, 24 had nidus-type AVMs and 4 had
      fistulas. SAMS were more prevalent in females (71% versus 48%), and also
      presented earlier than non-SAMS SCAVMs. Intradural hemorrhage (SAH or
      hematomyelia) was the most common presentation and more common than in non-SAMS
      lesions. Twenty-six patients underwent embolization of the intradural lesion in
      50 sessions. Thirteen patients underwent treatment of intradural aneurysms in 16
      sessions. Six patients underwent embolization of extradural lesions in 16
      sessions. Twenty-three patients had an average of 94 months of clinical follow-up
      (3-309 months) after the first treatment, during which 5 patients had
      hemorrhages. Angiographic follow-up was performed in 20 patients at an average of
      85 months (range, 3-309 months), which showed new development or enlargement of
      an aneurysm in 5 patients. This type of angiographic progression was more common
      in patients with SAMS. CONCLUSIONS: SAMS most commonly presents with hemorrhage
      from the SCAVM. Endovascular embolization can be performed safely with good
      functional outcome, though most patients clinically deteriorate in the long term.
      Periodic angiographic follow-up with intent to perform preventive target
      embolization is important to control the disease.

PMID- 22859289
TI  - Evaluating CT perfusion using outcome measures of delayed cerebral ischemia in
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH
      and remains a leading cause of morbidity and mortality. Our aim was to evaluate
      CTP in aneurysmal SAH by using outcome measures of DCI. MATERIALS AND METHODS:
      This was a retrospective study of consecutive patients with SAH enrolled in a
      prospective institutional review board-approved clinical accuracy trial.
      Qualitative CTP deficits were determined by 2 neuroradiologists blinded to
      clinical and imaging data. Quantitative CTP was performed by using a standardized
      protocol with region-of-interest placement sampling of the cortex. Primary
      outcome measures were permanent neurologic deficits and infarction. The secondary
      outcome measure was DCI, defined as clinical deterioration. CTP test
      characteristics (95% CI) were determined for each outcome measure. Statistical
      significance was calculated by using the Fisher exact and Student t tests. ROC
      curves were generated to determine accuracy and threshold analysis. RESULTS:
      Ninety-six patients were included. Permanent neurologic deficits developed in 33%
      (32/96). CTP deficits were seen in 78% (25/32) of those who developed permanent
      neurologic deficits and 34% (22/64) of those without (P < .0001). CTP deficits
      had 78% (61%-89%) sensitivity, 66% (53%-76%) specificity, and 53% (39%-67%)
      positive and 86% (73%-93%) negative predictive values. Infarction occurred in 18%
      (17/96). CTP deficits were seen in 88% (15/17) of those who developed infarction
      and 41% (32/79) of those without (P = .0004). CTP deficits had an 88% (66%-97%)
      sensitivity, 59% (48%-70%) specificity, and 32% (20%-46%) positive and 96% (86%
      99%) negative predictive values. DCI was diagnosed in 50% (48/96). CTP deficits
      were seen in 81% (39/48) of patients with DCI and in 17% (8/48) of those without
      (P < .0001). CTP deficits had 81% (68%-90%) sensitivity, 83% (70%-91%)
      specificity, and 83% (70%-91%) positive and 82% (69%-90%) negative predictive
      values. Quantitative CTP revealed significantly reduced CBF and prolonged MTT for
      DCI, permanent neurologic deficits, and infarction. ROC analysis showed that CBF
      and MTT had the highest accuracy. CONCLUSIONS: CTP may add prognostic information
      regarding DCI and poor outcomes in aneurysmal SAH.

PMID- 22859291
TI  - Checking the harness: safety for living liver donors.
AB  - KEY POINTS: 1. Expertise in hepatobiliary surgery. 2. Donor selection criteria.
      3. Selective liver biopsy in donors. 4. Accurate determination of hepatic volumes
      and anatomy. 5. Extent of donor hepatectomy. 6. Donor psychosocial evaluation. 7.
      Catastrophic events. 8. Long-term follow up.

PMID- 22859290
TI  - Estimation of gene-environment interaction by pooling biospecimens.
AB  - Case-control studies are prone to low power for testing gene-environment
      interactions (GXE) given the need for a sufficient number of individuals on each
      strata of disease, gene, and environment. We propose a new study design to
      increase power by strategically pooling biospecimens. Pooling biospecimens allows
      us to increase the number of subjects significantly, thereby providing
      substantial increase in power. We focus on a special, although realistic case,
      where disease and environmental statuses are binary, and gene status is ordinal
      with each individual having 0, 1, or 2 minor alleles. Through pooling, we obtain
      an allele frequency for each level of disease and environmental status. Using the
      allele frequencies, we develop a new methodology for estimating and testing GXE
      that is comparable to the situation when we have complete data on gene status for
      each individual. We also explore the measurement process and its effect on the
      GXE estimator. Using an illustration, we show the effectiveness of pooling with
      an epidemiologic study, which tests an interaction for fiber and paraoxonase on
      anovulation. Through simulation, we show that taking 12 pooled measurements from
      1000 individuals achieves more power than individually genotyping 500
      individuals. Our findings suggest that strategic pooling should be considered
      when an investigator designs a pilot study to test for a GXE.

PMID- 22859292
TI  - Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess:
      a causative link to polycystic ovarian syndrome.
AB  - Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is
      ubiquitously expressed and implicated in the protection against cellular damage
      because of cytotoxic metabolites such as advanced glycation end products (AGEs).
      Recently, ovarian tissue has emerged as a new target of excessive AGE deposition
      and has been associated with either a high AGE diet in experimental animals or
      hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans.
      This study was designed to investigate the impact of dietary AGEs and androgens
      in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18)
      and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were
      further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3
      months. The activity of ovarian GLO-I was significantly reduced in normal NAN
      animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I
      activity was markedly reduced in AN animals compared with NAN (p <= 0.001) when
      fed with the corresponding diet type. In addition, ovarian GLO-I activity was
      positively correlated with the body weight gain (r(s) = 0.533, p < 0.001),
      estradiol (r(s) = 0.326, p = 0.033) and progesterone levels (r(s) = 0.500, p <
      0.001). A negative correlation was observed between GLO-I activity and AGE
      expression in the ovarian granulosa cell layer of all groups with marginal
      statistical significance (r(s) = -0.263, p = 0.07). The present data demonstrate
      that ovarian GLO-I activity may be regulated by dietary composition and androgen
      levels. Modification of ovarian GLO-I activity, observed for the first time in
      this androgenized prepubertal rat model, may present a contributing factor to the
      reproductive dysfunction characterizing PCOS.

PMID- 22859293
TI  - Regulator of G-protein signaling 3 isoform 1 (PDZ-RGS3) enhances canonical Wnt
      signaling and promotes epithelial mesenchymal transition.
AB  - The Wnt beta-catenin pathway controls numerous cellular processes including cell
      differentiation and cell-fate decisions. Wnt ligands engage Frizzled receptors
      and the low-density-lipoprotein-related protein 5/6 (LRP5/6) receptor complex
      leading to the recruitment of Dishevelled (Dvl) and Axin1 to the plasma membrane.
      Axin1 has a regulator of G-protein signaling (RGS) domain that binds adenomatous
      polyposis coli and Galpha subunits, thereby providing a mechanism by which Galpha
      subunits can affect beta-catenin levels. Here we show that Wnt signaling enhances
      the expression of another RGS domain-containing protein, PDZ-RGS3. Reducing PDZ
      RGS3 levels impaired Wnt3a-induced activation of the canonical pathway. PDZ-RGS3
      bound GSK3beta and decreased its catalytic activity toward beta-catenin. PDZ-RGS3
      overexpression enhanced Snail1 and led to morphological and biochemical changes
      reminiscent of epithelial mesenchymal transition (EMT). These results indicate
      that PDZ-RGS3 can enhance signals generated by the Wnt canonical pathway and that
      plays a pivotal role in EMT.

PMID- 22859294
TI  - Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells
      through p53-dependent and -independent mechanisms.
AB  - Annexin A2 (ANXA2) overexpression is required for cancer cell proliferation;
      however, the molecular mechanisms underlying ANXA2-mediated regulation of the
      cell cycle are still unknown. ANXA2 is highly expressed in non-small cell lung
      cancer (NSCLC) and is positively correlated with a poor prognosis. NSCLC A549
      cells lacking ANXA2 exhibited defects in tumor growth in vivo and in cell
      proliferation in vitro without cytotoxicity. ANXA2 knockdown induced cell cycle
      arrest at G(2) phase. Unexpectedly, ANXA2 silencing increased the expression of
      p53 and its downstream genes, which resulted in p53-dependent and -independent
      G(2) arrest. Aberrant JNK inactivation, which was observed in ANXA2-deficient
      cells, inhibited cell proliferation following G(2) arrest. A lack of ANXA2 caused
      a loss of JNK-regulated c-Jun expression, resulting in an increase in p53
      transcription. These results demonstrate a novel role for ANXA2 in NSCLC cell
      proliferation by facilitating the cell cycle partly through the regulation of p53
      via JNK/c-Jun.

PMID- 22859295
TI  - Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion
      polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) zeta, and
      Pol kappa.
AB  - DNA synthesis across lesions during genomic replication requires concerted
      actions of specialized DNA polymerases in a potentially mutagenic process known
      as translesion synthesis. Current models suggest that translesion synthesis in
      mammalian cells is achieved in two sequential steps, with a Y-family DNA
      polymerase (kappa, eta, iota, or Rev1) inserting a nucleotide opposite the lesion
      and with the heterodimeric B-family polymerase zeta, consisting of the catalytic
      Rev3 subunit and the accessory Rev7 subunit, replacing the insertion polymerase
      to carry out primer extension past the lesion. Effective translesion synthesis in
      vertebrates requires the scaffolding function of the C-terminal domain (CTD) of
      Rev1 that interacts with the Rev1-interacting region of polymerases kappa, eta,
      and iota and with the Rev7 subunit of polymerase zeta. We report the purification
      and structure determination of a quaternary translesion polymerase complex
      consisting of the Rev1 CTD, the heterodimeric Pol zeta complex, and the Pol kappa
      Rev1-interacting region. Yeast two-hybrid assays were employed to identify
      important interface residues of the translesion polymerase complex. The
      structural elucidation of such a quaternary translesion polymerase complex
      encompassing both insertion and extension polymerases bridged by the Rev1 CTD
      provides the first molecular explanation of the essential scaffolding function of
      Rev1 and highlights the Rev1 CTD as a promising target for developing novel
      cancer therapeutics to suppress translesion synthesis. Our studies support the
      notion that vertebrate insertion and extension polymerases could structurally
      cooperate within a megatranslesion polymerase complex (translesionsome) nucleated
      by Rev1 to achieve efficient lesion bypass without incurring an additional
      switching mechanism.

PMID- 22859296
TI  - Structural basis of recruitment of DNA polymerase zeta by interaction between
      REV1 and REV7 proteins.
AB  - REV1, REV3, and REV7 are pivotal proteins in translesion DNA synthesis, which
      allows DNA synthesis even in the presence of DNA damage. REV1 and REV3 are error
      prone DNA polymerases and function as inserter and extender polymerases in this
      process, respectively. REV7 interacts with both REV1 and REV3, acting as an
      adaptor that functionally links the two, although the structural basis of this
      collaboration remains unclear. Here, we show the crystal structure of the ternary
      complex, composed of the C-terminal domain of human REV1, REV7, and a REV3
      fragment. The REV1 C-terminal domain adopts a four-helix bundle that interacts
      with REV7. A linker region between helices 2 and 3, which is conserved among
      mammals, interacts with the beta-sheet of REV7. Remarkably, the REV7-binding
      interface is distinct from the binding site of DNA polymerase eta or kappa. Thus,
      the REV1 C-terminal domain might facilitate polymerase switching by providing a
      scaffold for both inserter and extender polymerases to bind. Our structure
      reveals the basis of DNA polymerase zeta (a complex of REV3 and REV7) recruitment
      to the stalled replication fork and provides insight into the mechanism of
      polymerase switching.

PMID- 22859297
TI  - Progranulin: a proteolytically processed protein at the crossroads of
      inflammation and neurodegeneration.
AB  - GRN mutations cause frontotemporal lobar degeneration with TDP-43-positive
      inclusions. The mechanism of pathogenesis is haploinsufficiency. Recently,
      homozygous GRN mutations were detected in two patients with neuronal ceroid
      lipofuscinosis, a lysosomal storage disease. It is unknown whether the
      pathogenesis of these two conditions is related. Progranulin is cleaved into
      smaller peptides called granulins. Progranulin and granulins are attributed with
      roles in cancer, inflammation, and neuronal physiology. Cell surface receptors
      for progranulin, but not granulin peptides, have been reported. Revealing the
      cell surface receptors and the intracellular functions of granulins and
      progranulin is crucial for understanding their contributions to
      neurodegeneration.

PMID- 22859298
TI  - Raf-1 kinase inhibitory protein (RKIP) mediates ethanol-induced sensitization of
      secretagogue signaling in pancreatic acinar cells.
AB  - Excessive alcohol consumption is associated with most cases of chronic
      pancreatitis, a progressive necrotizing inflammatory disease that can result in
      pancreatic insufficiency due to acinar atrophy and fibrosis and an increased risk
      of pancreatic cancer. At a cellular level acute alcohol exposure can sensitize
      pancreatic acinar cells to secretagogue stimulation, resulting in dysregulation
      of intracellular Ca(2+) homeostasis and premature digestive enzyme activation;
      however, the molecular mechanisms by which ethanol exerts these toxic effects
      have remained undefined. In this study we identify Raf-1 kinase inhibitory
      protein as an essential mediator of ethanol-induced sensitization of
      cholecystokinin- and carbachol-regulated Ca(2+) signaling in pancreatic acinar
      cells. We show that exposure of rodent acinar cells to ethanol induces protein
      kinase C-dependent Raf-1 kinase inhibitory protein phosphorylation, sensitization
      of cholecystokinin-stimulated Ca(2+) signaling, and potentiation of both basal
      and cholecystokinin-stimulated extracellular signal-regulated kinase activation.
      Furthermore, we show that either suppression of Raf-1 kinase inhibitory protein
      expression using short hairpin RNA or gene ablation prevented the sensitizing
      effects of ethanol on cholecystokinin- and carbachol-stimulated Ca(2+) signaling
      and intracellular chymotrypsin activation in pancreatic acinar cells, suggesting
      that the modulation of Raf-1 inhibitory protein expression may have future
      therapeutic utility in the prevention or treatment of alcohol-associated
      pancreatitis.

PMID- 22859299
TI  - Determination of ligand pathways in globins: apolar tunnels versus polar gates.
AB  - Although molecular dynamics simulations suggest multiple interior pathways for
      O(2) entry into and exit from globins, most experiments indicate well defined
      single pathways. In 2001, we highlighted the effects of large-to-small amino acid
      replacements on rates for ligand entry and exit onto the three-dimensional
      structure of sperm whale myoglobin. The resultant map argued strongly for ligand
      movement through a short channel from the heme iron to solvent that is gated by
      the distal histidine (His-64(E7)) near the solvent edge of the porphyrin ring. In
      this work, we have applied the same mutagenesis mapping strategy to the neuronal
      mini-hemoglobin from Cerebratulus lacteus (CerHb), which has a large internal
      tunnel from the heme iron to the C-terminal ends of the E and H helices, a
      direction that is 180 degrees  opposite to the E7 channel. Detailed comparisons
      of the new CerHb map with expanded results for Mb show unambiguously that the
      dominant (>90%) ligand pathway in CerHb is through the internal tunnel, and the
      major (>75%) ligand pathway in Mb is through the E7 gate. These results
      demonstrate that: 1) mutagenesis mapping can identify internal pathways when they
      exist; 2) molecular dynamics simulations need to be refined to address
      discrepancies with experimental observations; and 3) alternative pathways have
      evolved in globins to meet specific physiological demands.

PMID- 22859300
TI  - The methionine-aromatic motif plays a unique role in stabilizing protein
      structure.
AB  - Of the 20 amino acids, the precise function of methionine (Met) remains among the
      least well understood. To establish a determining characteristic of methionine
      that fundamentally differentiates it from purely hydrophobic residues, we have
      used in vitro cellular experiments, molecular simulations, quantum calculations,
      and a bioinformatics screen of the Protein Data Bank. We show that approximately
      one-third of all known protein structures contain an energetically stabilizing
      Met-aromatic motif and, remarkably, that greater than 10,000 structures contain
      this motif more than 10 times. Critically, we show that as compared with a purely
      hydrophobic interaction, the Met-aromatic motif yields an additional
      stabilization of 1-1.5 kcal/mol. To highlight its importance and to dissect the
      energetic underpinnings of this motif, we have studied two clinically relevant
      TNF ligand-receptor complexes, namely TRAIL-DR5 and LTalpha-TNFR1. In both cases,
      we show that the motif is necessary for high affinity ligand binding as well as
      function. Additionally, we highlight previously overlooked instances of the motif
      in several disease-related Met mutations. Our results strongly suggest that the
      Met-aromatic motif should be exploited in the rational design of therapeutics
      targeting a range of proteins.

PMID- 22859301
TI  - Synergistic effects of interleukin-7 and pre-T cell receptor signaling in human T
      cell development.
AB  - The role of IL-7 in pre-T cell receptor (TCR) signaling during human T cell
      development is poorly understood. To study this, we engineered Molt3, a T cell
      progenitor T-acute lymphoblastic leukemia cell line, using lentiviral IL-7
      receptor alpha (IL-7Ralpha) to serve as a model system. IL-7 promoted pre-TCR
      activation in IL-7Ralpha(hi) Molt3 as illustrated by CD25 up-regulation after
      anti-CD3 stimulation. Anti-CD3 treatment activated Akt and Erk1/2 signaling
      pathways as proven using specific inhibitors, and IL-7 further enhanced both
      signaling pathways. The close association of IL-7Ralpha with CD3zeta in the pre
      TCR complex was illustrated through live imaging confocal fluorescence
      microscopy. These results demonstrate a direct and cooperative role of IL-7 in
      pre-TCR signaling.

PMID- 22859302
TI  - Activation of the epithelial sodium channel (ENaC) by the alkaline protease from
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that significantly
      contributes to the mortality of patients with cystic fibrosis. Chronic infection
      by Pseudomonas induces sustained immune and inflammatory responses and damage to
      the airway. The ability of Pseudomonas to resist host defenses is aided, in part,
      by secreted proteases, which act as virulence factors in multiple modes of
      infection. Recent studies suggest that misregulation of protease activity in the
      cystic fibrosis lung may alter fluid secretion and pathogen clearance by
      proteolytic activation of the epithelial sodium channel (ENaC). To evaluate the
      possibility that proteolytic activation of ENaC may contribute to the virulence
      of Pseudomonas, primary human bronchial epithelial cells were exposed to P.
      aeruginosa and ENaC function was assessed by short circuit current measurements.
      Apical treatment with a strain known to express high levels of alkaline protease
      (AP) resulted in an increase in basal ENaC current and a loss of trypsin
      inducible ENaC current, consistent with sustained activation of ENaC. To further
      characterize this AP-induced ENaC activation, AP was purified, and its folding,
      activity, and ability to activate ENaC were assessed. AP folding was efficient
      under pH and calcium conditions thought to exist in the airway surface liquid of
      normal and cystic fibrosis (CF) lungs. Short circuit measurements of ENaC in
      polarized monolayers indicated that AP activated ENaC in immortalized cell lines
      as well as post-transplant, primary human bronchial epithelial cells from both CF
      and non-CF patients. This activation was mapped to the gamma-subunit of ENaC.
      Based on these data, patho-mechanisms associated with AP in the CF lung are
      proposed wherein secretion of AP leads to decreased airway surface liquid volume
      and a corresponding decrease in mucocilliary clearance of pulmonary pathogens.

PMID- 22859303
TI  - Overexpression and beta-1,6-N-acetylglucosaminylation-initiated aberrant
      glycosylation of TIMP-1: a "double whammy" strategy in colon cancer progression.
AB  - There has been ongoing debate over whether tissue inhibitor of metalloproteinase
      1 (TIMP-1) is pro- or anti-oncogenic. We confirmed that TIMP-1 reinforced cell
      proliferation in an alphavbeta3 integrin-dependent manner and conferred
      resistance against cytotoxicity triggered by TNF-alpha and IL-2 in WiDr colon
      cancer cells. The cell-proliferative effects of TIMP-1 contributed to
      clonogenicity and tumor growth during the onset and early phase of tumor
      formation in vivo and in vitro. However, mass-produced TIMP-1 impeded further
      tumor growth by tightly inhibiting the activities of collagenases, which are
      critical for tumor growth and malignant transformation. Tumor cells could
      overcome this impasse by overexpression of N-acetylglucosaminyltransferase V,
      which deteriorates TIMP-1 into an aberrant glycoform. The aberrant glycoform of
      TIMP-1 was responsible for the mitigated inhibition of collagenases. The
      outbalanced activities of collagenases can degrade the basement membrane and the
      interstitial matrix, which act as a physical barrier for tumor growth and
      progression more efficiently. The concomitant overexpression of TIMP-1 and N
      acetylglucosaminyltransferase V enabled WiDr cells to show a higher tumor growth
      rate as well as more malignant behaviors in a three-dimensional culture system.

PMID- 22859304
TI  - Serratia marcescens induces apoptotic cell death in host immune cells via a
      lipopolysaccharide- and flagella-dependent mechanism.
AB  - Injection of Serratia marcescens into the blood (hemolymph) of the silkworm,
      Bombyx mori, induced the activation of c-Jun NH(2)-terminal kinase (JNK),
      followed by caspase activation and apoptosis of blood cells (hemocytes). This
      process impaired the innate immune response in which pathogen cell wall
      components, such as glucan, stimulate hemocytes, leading to the activation of
      insect cytokine paralytic peptide. S. marcescens induced apoptotic cell death of
      silkworm hemocytes and mouse peritoneal macrophages in vitro. We searched for S.
      marcescens transposon mutants with attenuated ability to induce apoptosis of
      silkworm hemocytes. Among the genes identified, disruption mutants of wecA (a
      gene involved in lipopolysaccharide O-antigen synthesis), and flhD and fliR
      (essential genes in flagella synthesis) showed reduced motility and impaired
      induction of mouse macrophage cell death. These findings suggest that S.
      marcescens induces apoptosis of host immune cells via lipopolysaccharide- and
      flagella-dependent motility, leading to the suppression of host innate immunity.

PMID- 22859305
TI  - p38alpha protein negatively regulates T helper type 2 responses by orchestrating
      multiple T cell receptor-associated signals.
AB  - Mitogen-activated protein kinase p38alpha is a critical regulator of certain
      inflammatory diseases. However, its role in T helper type 2 (Th2) responses and
      allergic inflammation remains unknown. Here we show an increase in the production
      of interleukin-4 (IL-4) in p38alpha(-/-) CD4(+) T cells in response to antigen
      stimulation. p38alpha-deficient naive CD4(+) T cells preferentially differentiate
      into Th2 cells through increased endogenous production of IL-4. Consistent with
      those results, we also observed decreased expression of p38alpha during T helper
      cell differentiation. Furthermore, deficiency of p38alpha alters the balance in
      the expression of NFATc1 and NFATc2 under steady-state conditions and enhances
      the expression and nuclear translocation of NFATc1 in CD4(+) T cells upon antigen
      stimulation. Knockdown of NFATc1 significantly inhibits Th2 differentiation in
      p38alpha(-/-) T cells but not in p38alpha(+/-) T cells. p38alpha deficiency also
      inhibits the activation of Akt but enhances the activation of ERK in response to
      T cell receptor engagement without impacting IL-2/Stat5 signaling. In a model of
      ovalbumin-induced acute allergic airway inflammation, mice with induced deletion
      of p38alpha show elevated serum ovalbumin-specific IgE level, increased
      infiltration of eosinophils, and higher concentrations of Th2 cytokines including
      IL-4 and IL-5 in the bronchoalveolar lavage fluid relative to control mice. Taken
      together, p38alpha regulates multiple T cell receptor-associated signals and
      negatively influences Th2 differentiation and allergic inflammation.

PMID- 22859306
TI  - TIPE2, a novel regulator of immunity, protects against experimental stroke.
AB  - The inflammatory responses accompanying stroke are recognized to contribute to
      secondary ischemic injury. TIPE2 is a very recently identified negative regulator
      of inflammation that maintains immune homeostasis. However, it is unknown whether
      TIPE2 is expressed in the brain and contributes to the regulation of cerebral
      diseases. In this study, we explored the potential roles of TIPE2 in cerebral
      ischemia/reperfusion injury. TIPE2(-/-) mice were used to assess whether TIPE2
      provides neuroprotection following cerebral ischemia/reperfusion induced by
      middle cerebral artery occlusion (MCAO), and in vitro primary cerebral cell
      cultures were used to investigate the expression and regulation of TIPE2. Our
      results show that genetic ablation of the Tipe2 gene significantly increased the
      cerebral volume of infarction and neurological dysfunction in mice subjected to
      MCAO. Flow cytometric analysis revealed more infiltrating macrophages,
      neutrophils, and lymphocytes in the ischemic hemisphere of TIPE2(-/-) mice. The
      responses to inflammatory cytokines and chemokines were significantly increased
      in TIPE2(-/-) mouse brain after MCAO. We further observed that TIPE2 was highly
      induced in WT mice after cerebral ischemia and was expressed mainly in
      microglia/macrophages, but not in neurons and astrocytes. Finally, we found that
      regulation of TIPE2 expression was associated with NADPH oxidase activity. These
      findings demonstrate, for the first time, that TIPE2 is involved in the
      pathogenesis of stroke and suggest that TIPE2 plays an essential role in a signal
      transduction pathway that links the inflammatory immune response to specific
      conditions after cerebral ischemia. Targeting TIPE2 may be a new therapeutic
      strategy for stroke treatment.

PMID- 22859307
TI  - Formyl peptide receptors from immune and vomeronasal system exhibit distinct
      agonist properties.
AB  - The formyl peptide receptor (Fpr) family is well known for its contribution to
      immune defense against pathogens in human and rodent leukocytes. Recently,
      several structurally related members of these receptors were discovered in
      sensory neurons of the mouse vomeronasal organ (VNO), key detectors of pheromones
      and related semiochemicals. Although the biological role of vomeronasal Fprs is
      not yet clear, the known contribution of other Fprs to host immune defense
      suggested that they could contribute to vomeronasal pathogen sensing. Precise
      knowledge about the agonist properties of mouse Fprs is required to determine
      their function. We expressed all seven mouse and three human Fprs using an in
      vitro system and tested their activation with 32 selected compounds by conducting
      high throughput calcium measurements. We found an intriguing functional
      conservation between human and mouse immune Fprs that is most likely a
      consequence of closely similar biological constraints. By contrast, our data
      suggest a neofunctionalization of the vomeronasal Fprs. We show that the
      vomeronasal receptor mFpr-rs1 can be activated robustly by W-peptide and
      structural derivatives but not by other typical ligands of immune Fprs. mFpr-rs1
      exhibits a stereo-selective preference for peptides containing d-amino acids. The
      same peptide motifs are contained in pathogenic microorganisms. Thus, the ligand
      profile of mFpr-rs1 is consistent with a role in vomeronasal pathogen sensing.

PMID- 22859308
TI  - Base of the measles virus fusion trimer head receives the signal that triggers
      membrane fusion.
AB  - The measles virus (MV) fusion (F) protein trimer executes membrane fusion after
      receiving a signal elicited by receptor binding to the hemagglutinin (H)
      tetramer. Where and how this signal is received is understood neither for MV nor
      for other paramyxoviruses. Because only the prefusion structure of the
      parainfluenza virus 5 (PIV5) F-trimer is available, to study signal receipt by
      the MV F-trimer, we generated and energy-refined a homology model. We used two
      approaches to predict surface residues of the model interacting with other
      proteins. Both approaches measured interface propensity values for patches of
      residues. The second approach identified, in addition, individual residues based
      on the conservation of physical chemical properties among F-proteins. Altogether,
      about 50 candidate interactive residues were identified. Through iterative cycles
      of mutagenesis and functional analysis, we characterized six residues that are
      required specifically for signal transmission; their mutation interferes with
      fusion, although still allowing efficient F-protein processing and cell surface
      transport. One residue is located adjacent to the fusion peptide, four line a
      cavity in the base of the F-trimer head, while the sixth residue is located near
      this cavity. Hydrophobic interactions in the cavity sustain the fusion process
      and contacts with H. The cavity is flanked by two different subunits of the F
      trimer. Tetrameric H-stalks may be lodged in apposed cavities of two F-trimers.
      Because these insights are based on a PIV5 homology model, the signal receipt
      mechanism may be conserved among paramyxoviruses.

PMID- 22859310
TI  - The German Aortic Valve Registry (GARY): a nationwide registry for patients
      undergoing invasive therapy for severe aortic valve stenosis.
AB  - Background The increasing prevalence of severe aortic valve defects correlates
      with the increase of life expectancy. For decades, surgical aortic valve
      replacement (AVR), under the use of extracorporeal circulation, has been the gold
      standard for treatment of severe aortic valve diseases. In Germany ~12,000
      patients receive isolated aortic valve surgery per year. For some time,
      percutaneous balloon valvuloplasty has been used as a palliative therapeutic
      option for very few patients. Currently, alternatives for the established
      surgical procedures such as transcatheter aortic valve implantation (TAVI) have
      become available, but there are only limited data from randomized studies or low
      volume registries concerning long-time outcome. In Germany, the implementation of
      this new technology into hospital care increased rapidly in the past few years.
      Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010
      including all available therapeutic options and providing data from a large
      quantity of patients.Methods The GARY is assembled as a complete survey for all
      invasive therapies in patients with relevant aortic valve diseases. It evaluates
      the new therapeutic options and compares them to surgical AVR. The model for data
      acquisition is based on three data sources: source I, the mandatory German
      database for external performance measurement; source II, a specific registry
      dataset; and source III, a follow-up data sheet (generated by phone interview).
      Various procedures will be compared concerning observed complications, mortality,
      and quality of life up to 5 years after the initial procedure. Furthermore, the
      registry will enable a compilation of evidence-based indication criteria and, in
      addition, also a comparison of all approved operative procedures, such as Ross or
      David procedures, and the use of different mechanical or biological aortic valve
      prostheses.Results Since the launch of data acquisition in July 2010, almost all
      institutions performing aortic valve procedures in Germany joined the registry.
      By now, 91 sites which perform TAVI in Germany participate and more than 15,000
      datasets are already in the registry.Conclusion The implementation of new or
      innovative medical therapies needs supervision under the conditions of a well
      structured scientific project. Up to now relevant data for implementation of TAVI
      and long-term results are missing. In contrast to randomized controlled trials,
      GARY is a prospective, controlled, 5-year observational multicenter registry, and
      a real world investigation with only one exclusion criterion, the absence of
      patients' written consent.

PMID- 22859309
TI  - The increase in O-linked N-acetylglucosamine protein modification stimulates
      chondrogenic differentiation both in vitro and in vivo.
AB  - Insulin is an inducer of chondrocyte hypertrophy and growth plate chondrogenesis,
      although the specific molecular mechanisms behind these effects are mostly
      unknown. Our aim was to investigate whether insulin-induced chondrocyte
      hypertrophy occurs through a modification in the amount of O-linked N
      acetylglucosamine (O-GlcNAc)-modified proteins and in the expression of the key
      enzymes of this pathway, O-GlcNAc transferase and O-GlcNAcase (OGA). We also
      studied if O-GlcNAc accumulation per se, induced by an OGA inhibitor, was able to
      induce pre-hypertrophic chondrocyte differentiation both in vitro and in vivo.
      Insulin-induced differentiation of ATDC5 pre-chondrocytes occurred alongside a
      gradual increase in the accumulation of O-GlcNac-modified proteins (O
      GlcNAcylated proteins), as well as an increase in the expression of O-GlcNAc
      transferase and OGA. In the absence of insulin, O-GlcNAc accumulation induced by
      thiamet-G, a specific OGA inhibitor, was able to increase the gene expression of
      differentiation markers, as well as the activity of MMP-2 and -9. Thiamet-G also
      activated pERK, p-JNK, and p-p38 and the O-GlcNAcylation of Akt. Thiamet-G
      administration to C57/bl mice induced a significant expansion in the growth plate
      height and in the hypertrophic zone height. Therefore, our results show that O
      GlcNAc glycosylation has chondromodulating activity.

PMID- 22859311
TI  - Solid lipid nanoparticles of paclitaxel strengthened by hydroxypropyl-beta
      cyclodextrin as an oral delivery system.
AB  - The objective of this study was to evaluate the potential of surface-modified
      paclitaxel (PTX)-incorporated solid lipid nanoparticles with hydroxypropyl-beta
      cyclodextrin (smPSH). The smPSH released 89.70 +/- 3.99% of its entrapped PTX
      within 24 h when placed in dissolution medium containing sodium lauryl sulfate.
      The cellular uptake of PTX from smPSH in Caco-2 cells was 5.3-fold increased
      compared to a PTX solution based on a Taxol formulation. Moreover, smPSH showed
      an increased cytotoxicity compared to PTX solution. In addition, AUC (5.43
      ug*h/ml) and Cmax (1.44 ug/ml) of smPSH were higher than those (1.81 ug*h/ml and
      0.73 ug/ml) of PTX solution. The drug concentration of smPSH (11.12 +/- 4.45
      ng/mg of lymph tissue) in lymph nodes was higher than that of the PTX solution
      (0.89 +/- 0.75 ng/mg of lymph tissue), suggesting that more PTX was transported
      to the lymphatic vessels in the form of smPSH. In conclusion, smPSH have a
      potential as an alternative delivery system for oral administration of PTX.

PMID- 22859312
TI  - Toxicity of deoxynivalenol and its acetylated derivatives on the intestine:
      differential effects on morphology, barrier function, tight junction proteins,
      and mitogen-activated protein kinases.
AB  - The intestinal epithelium is the first barrier against food contaminants and is
      highly sensitive to mycotoxins, especially de oxynivalenol (DON). Consumption of
      DON-contaminated food is associated with outbreaks of gastroenteritis. In cereals
      and their byproducts, DON is present together with two acetylated derivatives, 3
      ADON and 15-ADON. The aim of this study was to compare the intestinal toxicity of
      DON and A-DONs, using noncytotoxic doses. The toxicity was assessed using in
      vitro (intestinal epithelial cell line), ex vivo (intestinal explants), and in
      vivo (animals exposed to mycotoxin-contaminated diets) models. The effects were
      studied on cell proliferation, barrier function, and intestinal structure. The
      mechanism of toxicity was investigated by measuring the expression of the tight
      junction proteins and of phosphorylated ERK1/2, p38, and JNK, which are effectors
      of signaling pathway involved in cellular programs including embryogenesis,
      proliferation, differentiation, and apoptosis. On proliferating cells, 3-ADON was
      less toxic than DON, which was less toxic than 15-ADON. On differentiated cells,
      15-ADON impaired the barrier function, whereas DON and 3-ADON did not have a
      significant effect. Similarly, ex vivo and in vivo, 15-ADON caused more
      histological lesions than DON or 3-ADON. At the molecular level, the 15-ADON
      activated the mitogen-activated protein kinases (MAPK) ERK1/2, p38, and JNK in
      the intestinal cell line, explants, and the jejunum from exposed animals at lower
      dose than DON and 3-ADON. Our results show that the higher toxicity of 15-DON is
      due to its ability to activate the MAPK. Given that cereal-based foods are
      contaminated with DON and acetylated-DON, the higher toxicity of 15-ADON should
      be taken into account.

PMID- 22859313
TI  - Heme and heme biosynthesis intermediates induce heme oxygenase-1 and cytochrome
      P450 2A5, enzymes with putative sequential roles in heme and bilirubin
      metabolism: different requirement for transcription factor nuclear factor
      erythroid- derived 2-like 2.
AB  - Cytochrome P450 2A5 (CYP2A5) oxidizes bilirubin to biliverdin and represents a
      putative candidate for maintaining bilirubin at safe but adequate antioxidant
      levels. Curiously, CYP2A5 is induced by both excessive heme and chemicals that
      inhibit heme synthesis. We hypothesized that heme homeostasis is a key modifier
      of Cyp2a5 expression via transcription factor nuclear factor erythroid-derived 2
      like 2 (Nrf2) and characterized the coordination of CYP2A5 and heme oxygenase-1
      (HMOX1) responses using wild-type and Nrf2(-/-) primary mouse hepatocytes. HMOX1
      was rapidly elevated by exogenous hemin, thereby limiting the transactivation of
      Cyp2a5 until high heme (> 5uM) exposure. Nrf2 was mandatory for CYP2A5 but not
      for HMOX1 induction by heme. CYP2A5 was intensively and HMOX1 moderately elevated
      in heme synthesis blockades by succinylacetone and N-methyl protoporphyrin IX,
      and Nrf2 partially mediated the induction of CYP2A5. Immunoelectron microscopy
      revealed that CYP2A5 is targeted Nrf2 dependently both to the endoplasmic
      reticulum (ER) and mitochondria. However, excessive heme increased CYP2A5
      predominantly in the ER. Phenobarbital, dibutyryl-cAMP, and peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      overexpression stimulate heme biosynthesis and induce CYP2A5. Acute but not
      chronic CYP2A5 induction by phenobarbital required Nrf2, whereas CYP2A5 induction
      by dibutyryl-cAMP and PGC-1alpha was potentiated by Nrf2 knockout. Collectively,
      heme homeostasis is established as a crucial regulator of hepatic Cyp2a5
      expression mediated via Nrf2 activation, whereas Nrf2 is redundant for Hmox1
      induction by heme. Similar subcellular targeting and coordination of CYP2A5 and
      HMOX1 responses suggest favorable conditions for enhanced CYP2A5-mediated
      bilirubin maintenance in altered heme homeostasis that predisposes to oxidative
      stress.

PMID- 22859314
TI  - New approaches to assess the transthyretin binding capacity of bioactivated
      thyroid hormone disruptors.
AB  - Polychlorinated biphenyls (PCBs) and polybrominated diphenyl-ethers (PBDEs) are
      metabolized into hydroxylated metabolites (OH-PCBs/PBDEs), which can disrupt the
      thyroid hormone homeostasis. Binding of these metabolites to transport proteins
      such as transthyretin (TTR) is an important mechanism of their toxicity. Several
      methods to quantify the competitive thyroxine (T(4)) displacement potency of pure
      metabolites exist. However, quantification of the potency of in vitro metabolized
      PCBs and PBDEs has drawbacks related to the coextraction of compounds disturbing
      the T(4)-TTR competitive binding assay. This study identifies and quantifies the
      major coextractants namely cholesterol, saturated and nonsaturated fatty acids
      (SFA and NSFA) at levels above 20 nmol per mg equivalent protein following
      various extraction methods. Their TTR binding potency was analyzed in a
      downscaled, nonradioactive fluorescence displacement assay. At concentration
      factors needed for TTR competitive binding, at least 10MUM of these coextracts is
      present, whereas individual SFA and NSFA disturb the assay from 0.3MUM. The
      effectiveness of the in vitro metabolism and extraction of the model compounds CB
      77 and BDE 47 was chemically quantified with a newly developed chromatographic
      method analyzing silylated derivatives of the OH-metabolites and coextractants. A
      new method to selectively extract metabolites and limit coextraction of
      disturbing compounds to less than 5 nmol per mg equivalent protein is presented.
      It is now possible to make a dose-response curve up to 50% inhibition with
      bioactivated CB 77 and BDE 47. The toxic potencies of bioactivated persistent
      organic pollutants (POPs) should be taken into account to prevent serious
      underestimation of their hazard and risk.

PMID- 22859315
TI  - A pharmacokinetic model of cis- and trans-permethrin disposition in rats and
      humans with aggregate exposure application.
AB  - Permethrin is a broad-spectrum pyrethroid insecticide and among the most widely
      used insecticides in homes and crops. Managing the risks for pesticides such as
      permethrin depends on the ability to consider diverse exposure scenarios and
      their relative risks. Physiologically based pharmacokinetic models of delta
      methrin disposition were modified to describe permethrin kinetics in the rat and
      human. Unlike formulated deltamethrin which consists of a single stereoisomer,
      permethrin is formulated as a blend of cis- and trans-diastereomers. We assessed
      time courses for cis-permethrin and trans-permethrin in several tissues (brain,
      blood, liver, and fat) in the rat following oral administration of 1 and 10mg/kg
      permethrin (cis/trans: 40/60). Accurate simulation of permethrin in the rat
      suggests that a generic model structure is promising for modeling pyrethroids.
      Human in vitro data and appropriate anatomical information were used to develop a
      provisional model of permethrin disposition with structures for managing oral,
      dermal, and inhalation routes of exposure. The human permethrin model was used to
      evaluate dietary and residential exposures in the U.S. population as estimated by
      EPA's Stochastic Human Exposure and Dose Simulation model. Simulated cis- and
      trans-DCCA, metabolites of permethrin, were  consistent with measured values in
      the National Health and Nutrition Examination Survey, indicating that the model
      holds promise for assessing population exposures and quantifying dose metrics.

PMID- 22859316
TI  - Application of fractional factorial designs to study drug combinations.
AB  - Herpes simplex virus type 1 (HSV-1) is known to cause diseases of various
      severities. There is increasing interest to find drug combinations to treat HSV-1
      by reducing drug resistance and cytotoxicity. Drug combinations offer potentially
      higher efficacy and lower individual drug dosage. In this paper, we report a new
      application of fractional factorial designs to investigate a biological system
      with HSV-1 and six antiviral drugs, namely, interferon alpha, interferon beta,
      interferon gamma, ribavirin, acyclovir, and tumor necrosis factor alpha. We show
      how the sequential use of two-level and three-level fractional factorial designs
      can screen for important drugs and drug interactions, as well as determine
      potential optimal drug dosages through the use of contour plots. Our initial
      experiment using a two-level fractional factorial design suggests that there is
      model inadequacy and that drug dosages should be reduced. A follow-up experiment
      using a blocked three-level fractional factorial design indicates that tumor
      necrosis factor alpha has little effect and that HSV-1 infection can be
      suppressed effectively by using the right combination of the other five antiviral
      drugs. These observations have practical implications in the understanding of
      antiviral drug mechanism that can result in better design of antiviral drug
      therapy.

PMID- 22859318
TI  - [Continuing the journey].

PMID- 22859317
TI  - Use of N-acetylcysteine during liver procurement: a prospective randomized
      controlled study.
AB  - Antioxidant agents have the potential to reduce ischemia/reperfusion damage to
      organs for liver transplantation (LT). In this prospective, randomized study, we
      tested the impact of an infusion of N-acetylcysteine (NAC) during liver
      procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts
      were transplanted into adult candidates with chronic liver disease who were
      listed for first LT, and according to a sequential, closed-envelope, single
      blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC
      protocol (69 patients) or to the standard protocol without NAC [71 patients (the
      control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1
      hour before the beginning of liver procurement and a locoregional NAC infusion
      (300 mg through the portal vein) just before cross-clamping. The primary endpoint
      was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%,
      respectively, in the NAC group and 82% and 70%, respectively, in the control
      group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on
      graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval
      (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14
      2.76, P <= 0.01). The incidence of postoperative complications was lower in the
      NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61
      patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the
      incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC
      group (15%) versus the control group (32%). In conclusion, the NAC harvesting
      protocol significantly improves graft survival. The effect of NAC on early graft
      function and survival seems higher when suboptimal grafts are used.

PMID- 22859319
TI  - [The beginning of a transcendent change in Archivos Argentinos de Pediatria].

PMID- 22859320
TI  - Original salbutamol versus similar salbutamol in children with asthma
      exacerbation: a randomized, controlled, double-blind study.
AB  - INTRODUCTION: There is clinical evidence suggesting that original salbutamol is
      more effective than a similar salbutamol product to revert symptoms in acute
      asthma exacerbation.. OBJECTIVE: To evaluate the bronchodilator response of both
      salbutamol medicinal products in children with asthma and to establish, based on
      the forced expiratory volume, if there is a difference between the group treated
      with the original salbutamol and the group treated with similar salbutamol.
      DESIGN: Prospective, randomized, controlled, double-blind study. MATERIAL AND
      METHODS: One hundred and twenty six children (63 boys, age 9.18 +/- 2.83 years
      old) were included. They were administered a dose of 20 drops (5 mg) of the
      original salbutamol or similar salbutamol product in nebulizing solution diluted
      only once in 2 ml saline solution. Pre- and post-bronchodilator, intra- and inter
      group forced expiratory volume was compared at baseline and at 30 minutes. The
      weight of salbutamol drops was determined by gravimetry, the concentration by
      chromatography and the number of drops by bottle. RESULTS: The bronchodilator
      response between the pre- and post-bronchodilator forced expiratory volume was
      225 ml (95% CI: 164-286) and 224 ml (95% CI: 163-284) for original salbutamol and
      similar salbutamol, respectively (p < 0.001). The Delta difference was 1.3 ml
      (95% CI: -86+83) (p = 0.97). The mean, standard deviation and variation
      coefficient percentage of the weight of the drop was 364.75 mg (+/- 6.01, 1.65)
      and 543.88 mg (+/- 56.09, 10.31) (p < 0.001) for original salbutamol and similar
      salbutamol, respectively. CONCLUSION: There were no differences in the
      bronchodilator response measured by FEV1 between the original salbutamol and a
      similar salbutamol product.

PMID- 22859321
TI  - Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in
      children, conducted in a tertiary-level university hospital: a randomized,
      controlled trial.
AB  - INTRODUCTION: Magnesium sulfate is a calcium antagonist that inhibits bronchial
      smooth muscle contraction promoting bronchodilation. It is used for the
      management of acute severe asthma in children; however most of the studies have
      been performed in adults. OBJECTIVE: To evaluate the effectiveness of intravenous
      magnesium sulfate for the treatment of pediatric patients with acute severe
      asthma exacerbations. POPULATION AND METHODS: A clinical, randomized, controlled
      trial was conducted between March 2006 and March 2011 at Hospital Universitario
      Austral. Children with acute severe asthma admitted to the emergency department
      were randomized into two groups. Group A (control group): standard protocol for
      the initial treatment of acute asthma exacerbation. Group B: treatment protocol
      with magnesium sulphate for acute severe asthma exacerbation. The primary outcome
      was the requirement of invasive or non invasive mechanical ventilation support.
      RESULTS: One hundred and forty three patients randomized into 2 groups were
      analyzed. The treatment group included 76 patients receiving magnesium sulfate
      within the first hour of the initiation of rescue treatment at the hospital, and
      the control group included 67 patients not treated with magnesium sulphate. Among
      the patients in the control group, 33% (n= 22) required mechanical ventilation
      support, compared to only 5% (n= 4) of the patients in the treatment group (p =
      0.001). CONCLUSIONS: Intravenous infusion of magnesium sulfate during the first
      hour of hospitalization in patients with acute severe asthma significantly
      reduced the percentage of children who required mechanical ventilation support.

PMID- 22859322
TI  - Systematic review: which topical agent is more efficacious in the prevention of
      infections in burn patients?
AB  - Topical agents are widely used in the care of burn patients; however the efficacy
      to prevent local infections and/or sepsis has not been clearly established in
      studies with a high level of evidence. This systematic review was conducted to
      assess the comparative efficacy among different topical agents. Material and
      Methods. The literature search was performed using the Medline database. Key MESH
      terms were: (burn* or scald*) AND (antibacterial or antibiotic*) AND (topic*) AND
      (therap* or prophylax*). Only randomized or quasi-randomized clinical trials,
      with a primary endpoint of local infection and/or sepsis were included. Studies
      were scored and classified regarding methodological key issues according to their
      level of evidence. Results. The initial search identified 457 studies of which 14
      were eligible for final evaluation, and full text was available for 11 of them.
      Conclusions. The evidence found in our review does not support differences in
      efficacy of topical agents to reduce sepsis and/or local infections in burn
      patients.

PMID- 22859323
TI  - Risk factors associated to clinical deterioration during the transport of sick
      newborn infants.
AB  - Adequate neonatal transport is a key component in the care of newborn infants
      that require transfer. Objective. To determine the characteristics and risk of
      clinical deterioration during neonatal transport. Material and Methods. This was
      an observational and prospective study that consecutively included newborn
      infants transferred to the Neonatal Intensive Care Unit (NICU) of the Hospital
      Garrahan. The TRIPS (Transport Risk Index of Physiology Stability) risk score was
      measured pre- and post-transport. A diagnosis of clinical deterioration was made
      when the post-transport TRIPS score was higher than the pre-transport score.
      Newborns characteristics, transport distance, newborns status upon admission,
      need for immediate cardiorespiratory support (ICRS), and death before the 7th day
      and at discharge were recorded. Bivariate and multivariate analyses were used to
      assess the associations with clinical deterioration . Results. A total of 160
      transferred newborn infants were enrolled, gestational age (GA) was 35 +/- 3
      weeks; birth weight (BW) 2482 +/- 904 g and median age 2 days. Most were referred
      due to cardiorespiratory (50%) or surgical (34%) illnesses. Of them, 91 (57%) had
      clinical deterioration and 46% hypothermia. Forty nine neonates required ICRS and
      28 died (twelve before 7 days after admittance). Variables assessed were not
      associated with the risk of clinical deterioration. Mortality was higher in the
      group with clinical deterioration (OR: 3.34; 95% CI: 1.2-8.7), even when severity
      of the clinical picture was considered (OR A: 3; 95% CI: 1.2-8.3). Clinical
      deterioration during transport was associated with the need for ICRS (OR: 2.4;
      95% CI: 1.2-5). Conclusions. In our experience transferred newborn infants often
      suffered loss of stability or clinical deterioration, regardless of their
      characteristics, and this was related to a higher mortality. Therefore, it is
      critical to optimize care strategies during all neonatal transports.

PMID- 22859324
TI  - [The thousand days opportunity for nutritional interventions: from conception to
      two years of life].

PMID- 22859325
TI  - [Child's subjectivity in postmodern times].
AB  - From mid '50s onwards, we witness a change of paradigm in the Western world: the
      expression of a historical shift from modernity to postmodernity. This new era
      includes a strong influence of the media on the population, a change from a
      lineal sense of time to a virtual, punctual one, and a flooding of overwhelming
      amount of information, mostly irrelevant, broadcasted in a de-contextualized,
      synchronic, fragmented and senseless fashion. This new age is characterized,
      above all, by the destitution of the State, the meta- institution source of
      legitimacy of all modern institutions: citizenship, factory, and mainly, School,
      an essential determinant this last one in the construction process of child
      subjectivity. Having lost its modeling power, the School loses its modern
      meaning, becoming thus a mere physical space in which pupils meet, but where
      general, transcendent rules, norms and values cannot be built, as in fact
      happened in modern times. According to Corea and Lewkowicz, school becomes an
      empty shed in which rules have to be built all the time, and become valid only
      for a particular occasion. These changes necessarily influence child
      subjectivity, the way they feel, they behave, and they "live" in contemporary
      society. Pediatricians have to be aware and try to understand these changes, so
      that we can help children, and, in doing so, to build a better world for them.

PMID- 22859326
TI  - [Enzyme replacement therapy in the infantile form of Pompe disease: Argentinean
      experience in a seven-year follow up case].
AB  - The infantile form of Pompe disease drives children to death before the first
      year of life due to cardiomyopathy and respiratory insufficiency. We present the
      seven-year follow-up experience with enzyme replacement therapy on a child with
      Pompe disease, being the longest follow-up in the country. The treatment was well
      tolerated without adverse reactions. The echocardiographic and
      electrocardiographic parameters clearly improved during the first year and remain
      stable. Motor milestones (like rolling over or sitting down without support) were
      initially achieved, but, after the third year were getting lost. The average age
      of ventilator dependence was also delayed (16 months). The 7-year old patient
      remains alive with severe generalized muscle weakness. The child notably overcame
      the average age of survival and onset of ventilator dependence. Although the
      cardiovascular improvement was clear, enzyme replacement therapy efficacy on
      skeletal muscle was limited in this patient.

PMID- 22859327
TI  - [Severe pertussis, progression and exchange transfusion as an alternative
      treatment. Case reports].
AB  - Pertussis is a contagious disease that may develop a serious clinical picture by
      hypoxemia and pulmonary hypertension refractory to treatment. The syndrome of
      hyperviscosity and arteriolar thrombosis is responsible for the cardiocirculatory
      collapse. Our objective is to describe the evolution of a series of patients with
      severe pertussis, some of whom received exchange transfusion (ET) as an
      alternative treatment. We analyzed 41 patients' clinical charts with diagnosis of
      pertussis treated in the Pediatric Intensive Care Units during the 2003-2011
      period. The mean age was 2.38 months. In the 90.2% of cases, the cause of
      admission to PICU was respiratory failure; 75% required mechanical respiratory
      support and 39% developed pulmonary hypertension. The overall mortality was
      41.4%. Nine patients were treated by ET, 5 died. Conclusion. Severe pertussis is
      associated with high mortality. ET reduced the mass of circulating leukocytes in
      53.5%; ET could be an alternative to conventional treatment, although controlled
      studies are required to assert it.

PMID- 22859328
TI  - [Metastatic infections in children with Staphylococcus aureus bacteremia].
AB  - Staphylococcus aureus is one of the most common infectious agents in children. It
      causes a broad spectrum of infections ranging from trivial to severe life
      threatening presentations. The possibility of complications in case of
      Staphylococcus aureus bacteremia (SAB) appears to be high, being described in up
      to 43% of cases in adult patients. However, metastatic infections seems to be
      less frequent in pediatric patients. There is no agreement on when or to whom
      complementary tests should be requested to rule them out. The aim of this study
      is to describe the frequency and characteristics of secondary impacts of SAB
      identified at "Hospital Gutierrez" in a period of two years, and assess potential
      risk factors for their occurrence. Metastatic infection rate was 15.8%. The main
      risk factor was the persistence of positive blood cultures more than 48 hours.

PMID- 22859329
TI  - [Surgery of intractable epilepsy in infants and adolescents. Case report].
AB  - Our objective is to present a series of 20 cases of children under 15 years
      operated on of intractable epilepsy in the last 12 years in Sanatorio Allende of
      Cordoba, based on medical records and follow up. Were included 8 patients with
      cortical dysplasias, 6 with tumors, 2 with Rasmussen syndrome, 1 with mesial
      gliosis, 1 with porencephalic cyst, 1 with gliosis due to traumatic brain injury,
      and 1 with encephalitis history. Localization was temporal in 9 cases and extra
      temporal in 11 cases (4 were frontal, 4 occipital, and 3 parietal). There was no
      surgical mortality. Patients with brain tumors present a satisfactory control
      over convulsive crises after tumor resection (Engel IA in 100%). Good results
      were also achieved in nontumor pathologies: 8 cases Engel IA, 1 Engel I B; 3
      cases Engel III A, one IV A and other IV C.

PMID- 22859330
TI  - [Transition in health care, from pediatrics to adult care].
AB  - The number of adolescent patients with chronic diseases and special heath needs
      are increasing, and they are reaching adulthood. Sometimes the passage to the
      adult health care is abrupt, depending upon the chronological age reached or
      because of an acute health problem that requires hospitalization. In order to
      facilitate the transition process, preparation of the child, the family and the
      health professionals involved is needed, as well as the coordination between the
      pediatric group and the adult team that will be incharge of the patient. This
      review shows the obstacles to this process and the recommended implementation
      steps required to a successful transition. It also describes the main aspects of
      a program that we implemented at the Hospital Italiano de Buenos Aires in
      conjunction with some departments of adult health care high lighting the main
      steps to follow before and during program's implementation.

PMID- 22859331
TI  - [Herpes encephalitis].

PMID- 22859332
TI  - [Child labour: a social problem that we are committed to].
AB  - Child labor is a complex problem that violates the fundamental rights of children
      and affects their psychophysical development. Child labor affects 215 million
      children in the world and 115 million perform activities defined as the "worst
      forms of child labor". Most child labor is in agriculture (60%), where the
      majority are unpaid family workers, compared to 26% in services and 7% in
      industry. Argentina has adopted the abolitionist position, promoting prevention
      and eradication within an inclusive public policy aimed to all children can
      exercise their rights. The Sociedad Argentina de Pediatria endorses this approach
      and proposes a course of action: the health team training, and dissemination of
      the risks of child labor and occupational teenager safety standards. As
      pediatricians we must be involved in defending children rights, and be able to
      detect any situation of child labor, and protect the health of children and
      adolescents. The joint interaction with family, community and other sectors of
      society will strengthen the network needed to implement child labor eradication
      policies.

PMID- 22859333
TI  - [Partial duplication of chromosome 4 in a patient with bilateral ocular
      coloboma].
AB  - Partial trisomy 4q is a rare chromosomal disease. It involves duplication of a
      portion (particularly the distal one) of the long arm of chromosome 4. In most
      cases results from a balanced translocation on one single progenitor. The "de
      novo" appearance is less common. Depending on the size and location of duplicated
      genetic material, patients may have different clinical manifestations. Associated
      eye pathology has been scarcely informed. We report on a novel case of a male
      infant with a proximal "de novo" 4q12-q22 duplication and bilateral iris, retinal
      and optic nerve coloboma.

PMID- 22859334
TI  - [Long chain 3-hydroxyacyl-coA dehydrogenase deficiency, association with HELLP
      and magnetic resonance spectroscopy findings].
AB  - LCHAD deficiency is a disorder of fatty acid beta oxidation. The most common
      clinical presentation includes disorders of consciousness, hypoglycemia and liver
      dysfunction triggered by prolonged fasting or infection. Once a metabolic crisis
      is triggered, there is a high mortality. HELLP syndrome and acute fatty liver
      failure of pregnancy (AFLP) are disorders of the third trimester of pregnancy.
      These diseases have been associated during pregnancy with hereditary defects of
      beta-oxidation in the fetus. We report a case of beta-oxidation disorder (LCHAD
      deficiency) associated with maternal HELLP. We described a peak of lipid and
      lactic on magnetic resonance spectroscopic of this patient. The investigation of
      these beta-oxidation disorders at birth, with a history of maternal HELLP, allows
      the diagnosis of the disease prior to developing symptoms.

PMID- 22859335
TI  - [Unusual branchial arch, dermoepidermal and nervous system anomalies in a neonate
      with VACTERL-H syndrome].
AB  - VACTERL-H syndrome is a complex disorder of congenital malformations that implies
      vertebrae, anus, heart, trachea, esophagus, kidneys, limbs and hydrocephalus. Its
      etiology has been identified in a fraction of patients largely due to their
      sporadic nature and its high degree of clinical heterogeneity. This report
      presents a newborn with VACTERL-H syndrome, associated with unusual branchial
      arch, dermoepidermal and nervous system anomalies, which are compared with those
      described in the medical literature. Based on our experience, the presentation of
      this case not only expands the knowledge of the spectrum of anomalies that can
      occur in VACTERL-H syndrome, but also can be useful in identifying patients with
      this heterogeneous phenotype.

PMID- 22859336
TI  - [Pulmonary hemorrhage associated with celiac disease].
AB  - Idiopathic pulmonary hemosiderosis is a severe and potentially fatal disease
      characterized by recurrent episodes of alveolar hemorrhage, hemoptysis, and
      anemia. His association with celiac disease, described as Lane- Hamilton
      syndrome, could be due to the fact that both entities share a common pathogenic
      immune pathway. We report two patients of 13 years who consulted for hemoptysis
      and severe anemia that had not responded to immunosuppressive treatment with
      pulses of methyl prednisolone, oral meprednisone and hydroxychloroquine. Although
      both children highlight the absence of gastrointestinal symptoms at the time of
      consultation, the dosage of anti-endomysial and anti-transglutaminase antibodies
      was positive and biopsy confirmed the presence of intestinal enteropathy. It is
      emphasized that in patients with diffuse alveolar hemorrhage, even in the absence
      of gastrointestinal symptoms, the concomitant presence of celiac disease should
      be evaluated. If celiac disease is present, the incorporation of a gluten-free
      diet helps to control the symptoms, allows reducing the immunosuppressive
      treatment and improves the clinical course of both entities.

PMID- 22859337
TI  - [Pantoea agglomerans: a new pathogen at the neonatal intensive care unit?].
AB  - Late-onset sepsis is very frequent among preterm infants and cases due to Gram
      negative pathogens have elevated morbidity and mortality. Pantoea agglomerans is
      a Gram negative organism which has been rarely reported causing disease in
      humans. We present a case of P. agglomerans late-onset fulminant sepsis in a
      preterm newborn at a neonatal intensive care unit. Up to date none P. agglomerans
      sepsis has been reported among this population in our country.

PMID- 22859338
TI  - [Extracorporeal membrane oxygenation and plasmapheresis in the treatment of
      severe pulmonary hemorrhage secondary to nodose polyarteritis].
AB  - We report to simultaneous use of extracorporeal life support (ECLS),
      plasmapheresis, hemodiafiltration and exogenous surfactant for the treatment of
      pulmonary hemorrhage, arterial hypertension, and renal failure secondary to
      nodose polyarteritis (NPA) in a 23-month-old patient. NPA is an autoimmune
      disease that affects small -and medium- caliber muscular arteries. Hypoxemia
      refractory to treatment with conventional and high frequency oscillatory
      ventilation was supported by ECMO while awaiting control of the autoimmune
      disease through the use of plasmapheresis and immunosuppressive treatment.
      Although the combination of ECLS with plasmapheresis is rare, it has been
      described during the management of cases of organ transplant, intoxication,
      cardiac failure, and sepsis. There are only two previous reports describing the
      use of this combined therapy for the treatment of pulmonary hemorrhage secondary
      to autoimmune vasculitis in childhood.

PMID- 22859339
TI  - Silencing of SNX1 by siRNA stimulates the ligand-induced endocytosis of EGFR and
      increases EGFR phosphorylation in gefitinib-resistant human lung cancer cell
      lines.
AB  - Gefitinib is known to suppress the activation of EGFR signaling, which is
      required for cell survival and proliferation in non-small cell lung cancer
      (NSCLC) cell lines. We previously demonstrated that the gefitinib-sensitive NSCLC
      cell line PC9 shows efficient ligand-induced endocytosis of phosphorylated EGFR
      (pEGFR). In contrast, the gefitinib-resistant NSCLC cell lines QG56 and A549
      showed internalized pEGFR accumulation in the aggregated early endosomes, and
      this was associated with SNX1, a protein that interacts with and enhances the
      degradation of EGFR upon EGF stimulation. In the present study, to investigate
      the role of SNX1 on EGF-stimulated EGFR/pEGFR endocytosis via the endocytic
      pathway, we examined the effect of depletion of SNX1 expression by siRNA in human
      NSCLC cell lines. Using immunofluorescence, we demonstrated that transfection of
      SNX1 siRNA into gefitinib-resistant NSCLC cells resulted in the disappearance of
      a large amounts of SNX1 staining. In addition, upon 15 min of EGF stimulation, we
      observed an efficient EGFR phosphorylation and a rapid endocytic delivery of
      pEGFR from early endosomes to late endosomes. Further, western blot analysis
      revealed that silencing of SNX1 expression by siRNA in the gefitinib-resistant
      cells leads to an accelerated degradation of EGFR along with a dramatic increase
      in the amounts of pEGFR after EGF stimulation. Based on these findings, we
      suggest that SNX1 is involved in the negative regulation of ligand-induced EGFR
      phosphorylation and mediates EGFR/pEGFR trafficking out of early endosomes for
      targeting to late endosomes/lysosomes via the early/late endocytic pathway in
      human lung cancer cells.

PMID- 22859340
TI  - Sample size planning for survival prediction with focus on high-dimensional data.
AB  - Sample size planning should reflect the primary objective of a trial. If the
      primary objective is prediction, the sample size determination should focus on
      prediction accuracy instead of power. We present formulas for the determination
      of training set sample size for survival prediction. Sample size is chosen to
      control the difference between optimal and expected prediction error. Prediction
      is carried out by Cox proportional hazards models. The general approach considers
      censoring as well as low-dimensional and high-dimensional explanatory variables.
      For dimension reduction in the high-dimensional setting, a variable selection
      step is inserted. If not all informative variables are included in the final
      model, the effect estimates are biased towards zero. The bias affects the
      prediction error, and its magnitude is influenced by the sample size. For
      variable selection, we consider two approaches: least absolute shrinkage and
      selection operator (LASCO) and univariable selection. For univariable selection,
      we can calculate input parameters for the sample size formula. For the LASCO,
      supportive simulations are necessary to appropriately choose the input
      parameters. We investigate the performance of the proposed formulas with the use
      of simulations. Simulation results support the validity of the sample size
      formulas. An application of a real data example illustrates the practical
      implementation of the method.

PMID- 22859341
TI  - Vitamin D receptor polymorphism rs2228570 (Fok1) is associated with rheumatoid
      arthritis in North American natives.
AB  - OBJECTIVE: Vitamin D (VitD) has immunomodulatory activity relevant to rheumatoid
      arthritis (RA) and acts by binding nuclear receptors that regulate gene
      transcription. VitD receptor polymorphisms have been variably associated with RA.
      Because North American Native (NAN) populations have a high prevalence of RA with
      a strong genetic contribution, we studied potential associations of the rs2228570
      (Fok1) VitD receptor polymorphism in a Canadian NAN population. METHODS: The
      single-nucleotide polymorphism (SNP) Fok1 was tested by sequencing NAN patients
      with RA (n=448) and unrelated NAN controls (n=704). Associations were tested
      using genotypic, dominant, and recessive models. RESULTS: The minor allele
      frequency (F/C) in the NAN control population was 0.44 and lower than reported in
      white subjects of the same geographical area. The Fok1 VitD receptor SNP was
      significantly associated with RA. Comparing patients with RA to unaffected NAN
      controls, the Fok1 SNP was associated with RA using both genotypic [FF vs Ff vs
      ff: RA 20%, 54%, 26% vs control 22%, 44%, 34% (chi-square 13.35, p=0.003)] and
      dominant models [FF/Ff vs ff: RA 74% vs 26% control 66% vs 34% (OR 1.5, 95% CI
      1.16-1.96, p=0.003)]. This association was strongest in shared-epitope-positive
      RA. CONCLUSION: VitD receptor polymorphisms may contribute to the high prevalence
      of RA in NAN populations.

PMID- 22859343
TI  - Efficacy of incentive spirometer exercise on pulmonary functions of patients with
      ankylosing spondylitis stabilized by tumor necrosis factor inhibitor therapy.
AB  - OBJECTIVE: To evaluate the effect of combining incentive spirometer exercise
      (ISE) with a conventional exercise (CE) on patients with ankylosing spondylitis
      (AS) stabilized by tumor necrosis factor (TNF) inhibitor therapy by comparing a
      combination group with a CE-alone group. METHODS: Forty-six patients (44 men, 2
      women) were randomized to the combination group (ISE plus CE; n=23) or the CE
      group (n=23). The CE regimen of both groups consisted of 20 exercises performed
      for 30 min once a day. The ISE was performed once a day for 30 min. The trial
      duration was 16 weeks. Patients were assessed before and at the end of treatment
      by measuring the Bath Ankylosing Spondylitis Disease Activity Index, Bath
      Ankylosing Spondylitis Functional Index (BASFI), chest expansion, finger to floor
      distance, pulmonary function measures, and 6-min walk distance. RESULTS: Both
      groups improved significantly in terms of chest expansion (p<0.01), finger to
      floor distance (p<0.01), and BASFI (p<0.05) after completing the exercise
      program. However, only the combination group showed significant improvements in
      the forced vital capacity (p<0.05), total lung capacity (p<0.01), and vital
      capacity (p<0.05). Although this did not achieve statistical significance, the
      combination group was mildly superior to the CE-alone group in functional
      disability and pulmonary function measures. CONCLUSION: Combining ISE with a CE
      can provide positive results in patients whose AS has been clinically stabilized
      by TNF inhibitor therapy.

PMID- 22859342
TI  - Do adult disease severity subclassifications predict use of cyclophosphamide in
      children with ANCA-associated vasculitis? An analysis of ARChiVe study treatment
      decisions.
AB  - OBJECTIVE: To determine whether adult disease severity subclassification systems
      for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are
      concordant with the decision to treat pediatric patients with cyclophosphamide
      (CYC). METHODS: We applied the European Vasculitis Study (EUVAS) and Wegener's
      Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems
      to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe).
      Modifications were made to the EUVAS and WGET systems to enable their application
      to this cohort of children. Treatment was categorized into 2 groups,
      "cyclophosphamide" and "no cyclophosphamide." Pearson's chi-square and Kendall's
      rank correlation coefficient statistical analyses were used to determine the
      relationship between disease severity subgroup and treatment at the time of
      diagnosis. RESULTS: In total, 125 children with AAV were studied. Severity
      subgroup was associated with treatment group in both the EUVAS (chi-square 45.14,
      p < 0.001, Kendall's tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p <
      0.001, Kendall's tau-b 0.689, p < 0.001) systems; however, 7 children classified
      by both systems as having less severe disease received CYC, and 6 children
      classified as having severe disease by both systems did not receive CYC.
      CONCLUSION: In this pediatric AAV cohort, the EUVAS and WGET adult severity
      subclassification systems had strong correlation with physician choice of
      treatment. However, a proportion of patients received treatment that was not
      concordant with their assigned severity subclass.

PMID- 22859344
TI  - Access to biologic therapies in Canada for children with juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To compare access to biologic therapies for children with juvenile
      idiopathic arthritis (JIA) across Canada, and to identify differences in
      provincial regulations and criteria for access. METHODS: Between June and August
      2010, we compiled the provincial guidelines for reimbursement of biologic drugs
      for children with JIA and conducted a multicenter Canada-wide survey of pediatric
      rheumatologists to determine their experience with accessing biologic therapies
      for their patients. RESULTS: There were significant difficulties accessing
      biologic treatments other than etanercept and abatacept for children. There were
      large discrepancies in the access criteria and coverage of biologic agents across
      provinces, notably with age restrictions for younger children. CONCLUSION:
      Canadian children with JIA may not receive optimal internationally recognized
      "standard" care because pediatric coverage for biologic drugs through provincial
      formularies is limited and inconsistent across the country. There is urgent need
      for public policy to improve access to biologic therapies for these children to
      ensure optimal short-term and longterm health outcomes.

PMID- 22859345
TI  - Palindromic rheumatism with positive anticitrullinated peptide/protein antibodies
      is not synonymous with rheumatoid arthritis. A longterm followup study.
AB  - OBJECTIVE: To analyze longterm progression to rheumatoid arthritis (RA) and the
      predictive value of anticitrullinated peptide/protein antibodies (ACPA) in
      palindromic rheumatism (PR). METHODS: We selected all patients in our clinic with
      PR who had at least 1 ACPA measurement. We included only patients with pure PR,
      defined as no evidence of associated rheumatic disease at the first serum ACPA
      measurement. Clinical characteristics, serum ACPA levels, duration of PR until
      serum ACPA measurement, and total followup time were recorded. The outcome
      variable was the definitive diagnosis of RA. The prognostic value of ACPA status
      in pure PR for a definite diagnosis of RA was analyzed by different statistical
      methods. RESULTS: Seventy-one patients (54 women/17 men) with a PR diagnosis were
      included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 +/- 4.7
      years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic
      disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The
      positive likelihood ratio of ACPA status for RA was 1.45, and the area under the
      receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45
      0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA
      negative patients (29.7% vs 14.7%), but the difference was not significant
      (hazard ratio 2.46, 95% CI 0.77-7.86). Mean ACPA levels of patients with pure PR
      did not differ significantly from those of patients who progressed to RA.
      CONCLUSION: ACPA are frequently found in the sera of patients with PR, and a
      significant proportion of these patients do not progress to RA in the long term.

PMID- 22859346
TI  - Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset
      Still's disease. An open, randomized, multicenter study.
AB  - OBJECTIVE: To study the efficacy of anakinra versus disease-modifying
      antirheumatic drugs (DMARD) in refractory adult-onset Still's disease (AOSD).
      METHODS: In a 24-week study, 22 patients with AOSD taking prednisolone >= 10
      mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was
      achievement of remission. RESULTS: At 8 and 24 weeks, 7/12 and 6/12 receiving
      anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced
      greater improvement in physical health measured by Medical Outcomes Study Short
      Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks,
      7/14 patients taking anakinra and 2/3 taking DMARD were in remission. CONCLUSION:
      Anakinra induced more beneficial responses than DMARD in patients with AOSD and
      was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration
      NCT01033656).

PMID- 22859347
TI  - Interleukin 21 correlates with T cell and B cell subset alterations in systemic
      lupus erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease
      characterized by alterations of the B cell subset, global regulatory T cell
      (Treg) depletion, and an increase in Th17 cells. Interleukin 21 (IL-21) plays a
      critical role in T cell and B cell homeostasis. Our objective was to determine
      the implication of IL-21 and IL-21-producing CD4+ T cells in the pathogenesis of
      SLE. METHODS: Twenty-five patients with SLE and 25 healthy donor controls were
      included. Analysis of CD4+ T cells producing IL-21, Th1, Th2, Th17, Treg,
      follicular helper T (TFH) cells, and B cells was performed in peripheral blood,
      and levels of cytokines were measured in culture supernatants. RESULTS:
      Circulating CD4+ T cells producing IL-21 were markedly expanded in patients with
      SLE compared to controls and were correlated with increased Th17, decreased Treg,
      and increased memory B cells. CD4+ T cells producing IL-21 were composed of
      CXCR5+ and CXCR5-CD4+ T cell subsets. Both IL-21-producing CXCR5+CD4+ T cells and
      CXCR5-CD4+ T cells were increased in patients with SLE, the CXCR5-CD4+ subset
      correlating with Th17 cells and Treg, while the CXCR5+CD4+ subset was correlated
      with alterations of the B cell subset. The CXCR5+CD4+ subset comprised mainly
      circulating Bcl6+CXCR5+CD4+ TFH cells that were markedly expanded in patients
      with SLE and were correlated with increased circulating Bcl6+CXCR5+ germinal
      center B cells. CONCLUSION: These findings suggest that IL-21, produced by
      distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell
      subsets in SLE, and that targeting IL-21 could provide beneficial effects on both
      T cell and B cell alterations.

PMID- 22859348
TI  - Natural killer cell cytolytic function in Korean patients with adult-onset
      Still's disease.
AB  - OBJECTIVE: To investigate natural killer (NK) cell proportions, NK cell
      cytotoxicity, and interleukin 18 (IL-18) expression, in patients with adult-onset
      Still's disease (AOSD). METHODS: Forty-five patients with AOSD (active = 22,
      inactive = 23) and 32 healthy controls were included. The proportions of NK cells
      among peripheral blood mononuclear cells were assessed by flow cytometry. IL-18
      and IL-18-binding protein (IL-18BP) concentrations were measured by ELISA. Twenty
      four patients with AOSD and 18 controls were examined for cytotoxic activity of
      NK cells by co-incubating NK cells with NK-sensitive K562 cells. The association
      of NK cell function with clinical and laboratory measures was investigated.
      RESULTS: The proportions of NK cells were significantly lower in patients with
      active AOSD than in patients with inactive disease and controls. NK cell
      cytotoxic function was significantly lower in patients with AOSD than in
      controls. NK cell proportions and cytotoxic functions were reexamined in 11 and 6
      patients, respectively, after treatment. Low NK cell proportion and cytotoxic
      dysfunction were improved with clinical improvements of the patients. IL-18 and
      IL-18BP levels were much higher in patients with active AOSD than in controls. NK
      cell cytotoxic functions were consistently low and IL-18 and IL-18BP levels were
      constantly high in patients with AOSD, regardless of disease activity.
      CONCLUSION: Low NK cell proportion, defective cytotoxic function, and elevated IL
      18 levels may be significant features of AOSD. After resolution of the acute
      phase, low NK cell proportion was recovered and NK cell cytolytic function was
      restored along with clinical improvement. These findings possibly contribute to
      immunologic abnormalities in AOSD.

PMID- 22859349
TI  - Knee enthesitis and synovitis on magnetic resonance imaging in patients with
      psoriasis without arthritic symptoms.
AB  - OBJECTIVE: This case-control study was designed to evaluate magnetic resonance
      imaging (MRI) findings of knee joints in patients with psoriasis without clinical
      peripheral or axial joint involvement, and to correlate MRI findings with disease
      and demographic variables. METHODS: In total 48 patients with psoriasis and no
      clinical evidence of synovitis or enthesitis in any peripheral or axial joints
      were enrolled. A random sample of 20 healthy subjects without knee or other joint
      complaints and matched for age and sex served as controls. All patients and
      controls underwent enhanced MRI studies of both knee joints, and MRI findings
      were compared. RESULTS: Among 48 patients (96 knees), a total of 90 entheseal
      lesions were detected, with no enthesitis in 2 cases (6.3%). Signs of continuing
      inflammation bilaterally were frequently found: soft tissue edema (STE; n = 52),
      bone marrow edema (BME; n = 20), perientheseal BME (n = 3), cartilaginous
      erosions (n = 42), and bone erosions (n = 27). In controls, 2 (10%) subjects had
      BME and another 5 (25%) showed cartilaginous erosions. None showed evidence of
      enthesitis. Significant correlations were observed between the number of
      entheseal lesions of both knees vs STE (present vs absent; r = 0.314, p = 0.030)
      and STE (number of lesions; r = 0.351, p = 0.014). Enthesitis (unilateral vs
      bilateral) was significantly and positively correlated with STE (r = 0.304, p =
      0.036), cartilaginous erosions (r = 0.304, p = 0.036), and villous projections (r
      = 0.347, p = 0.016). CONCLUSION: Subclinical synovitis and enthesitis are
      frequently found in the knee joint of patients with psoriasis. These may be an
      early sign of psoriatic arthritis.

PMID- 22859350
TI  - The acute-phase response is not predictive for the development of arthritis in
      seropositive arthralgia - a prospective cohort study.
AB  - OBJECTIVE: To evaluate whether markers of the acute-phase response in patients
      presenting with arthralgia and positive anticitrullinated protein antibodies
      (ACPA) and/or immunoglobulin M rheumatoid factor (IgM-RF) could be predictive for
      the development of arthritis. METHODS: In total, 137 ACPA- and/or IgM-RF-positive
      patients were included. Patients were followed annually for the development of
      arthritis, defined as presence of 1 or more swollen joints at clinical
      examination. High-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT),
      secretory phospholipase A2 (SPLA2), tumor necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6), IL-12p70, IL-10, and interferon-gamma (IFN-gamma) were
      measured in baseline serum samples. Gene expression focusing on a predefined
      panel of genes coding for inflammatory molecules was measured by multiplex
      ligation-dependent probe amplification. RESULTS: Thirty-five patients (26%)
      developed arthritis within a median time of 11 months (interquartile range 3.7-18
      mo). Circulating levels of cytokines, SPLA2, hsCRP, and PCT were not different
      between patients with progression to clinical arthritis and those without
      progression. However, a trend for IL-12p70, TNF-alpha, IL-10, IL-6, and SPLA2 was
      observed. No correlation between messenger RNA (mRNA) expression levels of
      inflammatory genes and progression to arthritis was found. Subgroup analysis of
      patients with early progression to arthritis showed higher levels of mRNA
      expression of poly(A)-specific ribonuclease and polycomb complex protein BMI-1
      compared to patients without progression to arthritis. CONCLUSION: Although low
      grade inflammation is present before onset of clinical arthritis in large cohorts
      and can be detected using consecutive measurements, a single measurement of acute
      phase reactants seems to have limited value for prediction of development of
      arthritis in individual patients.

PMID- 22859351
TI  - Longitudinal study of renal function in systemic sclerosis.
AB  - OBJECTIVE: To determine the prevalence of renal disease and the course of renal
      function over time in patients with systemic sclerosis (SSc). METHODS: We
      performed a multicenter, longitudinal study of 561 patients with SSc followed in
      the Canadian Scleroderma Research Group registry. Renal function was measured by
      the estimated creatinine clearance rate (eCcr) using the Cockcroft-Gault formula.
      Longitudinal changes in renal function were modeled using statistical analyses
      that adjusted for patient dropout. RESULTS: Among the study subjects, 112 (20%)
      had abnormal renal function with no history of scleroderma renal crisis (SRC) and
      29 (5%) had a history of SRC at baseline. In models adjusting for patient
      dropout, we found that patients with abnormal baseline renal function experienced
      the same annual decline in eCcr as patients with normal baseline renal function (
      0.89% per year, 95% CI -2.02%, 0.26%), which is similar to that observed in the
      general population. Patients with a history of SRC also showed the same rate of
      decline, although starting from a lower baseline. CONCLUSION: Renal dysfunction
      is common in SSc, even among those without a history of SRC. It is generally mild
      and renal function declines at a rate similar to the general population. These
      data are of considerable prognostic value for clinicians caring for patients with
      SSc.

PMID- 22859352
TI  - Blau arteritis resembling Takayasu disease with a novel NOD2 mutation.
AB  - OBJECTIVE: To put forward a new concept--Blau arteritis, a form of large-vessel
      vasculitis phenotypically related to Takayasu disease but genetically and
      clinically part of an expanded phenotype of Blau syndrome. METHODS: We provide a
      clinical description of a new case and summarize previously published cases of
      arteritis associated with Blau syndrome. Genetic testing was performed by direct
      sequencing of exon 4 of the NOD2 gene. RESULTS: The case described and those
      reviewed from the literature demonstrate the emerging phenotype of Takayasu-like
      arteritis in patients with Blau syndrome. Although most patients described to
      date depict an otherwise classic Blau syndrome phenotype, the current case was
      atypical in that the predominant features were arteritic. A novel substitution,
      G464W, in a highly conserved position near the nucleotide oligomerization domain
      of the NOD2 protein is also described. CONCLUSION: Blau arteritis can be observed
      in the context of both typical and atypical (incomplete) Blau syndrome. The
      associated mutation in the NOD2 gene raises the question of the potential
      importance of this gene among patients with "primary" forms of Takayasu
      arteritis.

PMID- 22859353
TI  - Hydroxychloroquine use is associated with lower odds of persistently positive
      antiphospholipid antibodies and/or lupus anticoagulant in systemic lupus
      erythematosus.
AB  - OBJECTIVE: Antiphospholipid antibodies (aPL) play an active role in the
      pathogenesis of the antiphospholipid syndrome (APS). Primary prevention in APS
      may be aimed at decreasing existing elevated aPL levels, or preventing high aPL
      titers and/or lupus anticoagulant (LAC) from developing in the first place.
      Hydroxychloroquine (HCQ) has been shown in retrospective studies to decrease aPL
      titers in laboratory studies, and to decrease thrombosis risk in patients with
      systemic lupus erythematosus (SLE). We investigated an association between HCQ
      use and persistent aPL and/or LAC in SLE. METHODS: We identified all patients
      over 21 years old with SLE from an urban tertiary care center who had aPL and LAC
      measured on at least 2 occasions at least 12 weeks apart. We defined the presence
      of persistent LAC+ and/or at least 1 aPL >= 40 U [immunoglobulin A (IgA), IgG, or
      IgM] as the main outcome variable. RESULTS: Among 90 patients included in the
      study, 17 (19%) had persistent LAC+ and/or at least 1 aPL >= 40 U. HCQ use was
      associated with significantly lower odds of having persistent LAC+ and/or aPL >=
      40 U (OR 0.21, 95% CI 0.05, 0.79, p = 0.02), adjusted for age, ethnicity, and
      sex. CONCLUSION: This is the first study to show that HCQ use is associated with
      lower odds of having persistently positive LAC and/or aPL. Data from this study
      provide a basis for the design of future prospective studies investigating the
      role of HCQ in primary and secondary prevention of APS.

PMID- 22859354
TI  - Disease-modifying antirheumatic drug use in the treatment of juvenile idiopathic
      arthritis: a cross-sectional analysis of the CARRA Registry.
AB  - OBJECTIVE: To characterize disease-modifying antirheumatic drug (DMARD) use for
      children with juvenile idiopathic arthritis (JIA) in the United States and to
      determine patient factors associated with medication use. METHODS: We analyzed
      cross-sectional baseline enrollment data from the Childhood Arthritis and
      Rheumatology Research Alliance (CARRA) Registry from May 2010 through May 2011
      for children with JIA. Current and prior medication use was included. We used
      parsimonious backward stepwise logistic regression models to calculate OR to
      estimate associations between clinical patient factors and medication use.
      RESULTS: We identified 2748 children with JIA with a median disease duration of
      3.9 years from 51 US clinical sites. Overall, 2023 (74%) had ever received a
      nonbiologic DMARD and 1246 (45%) had ever received a biologic DMARD. Among
      children without systemic arthritis, methotrexate use was most strongly
      associated with uveitis (OR 5.2, 95% CI 3.6-7.6), anticitrullinated protein
      antibodies (OR 4.5, 95% CI 1.7-12), and extended oligoarthritis (OR 4.1, 95% CI
      2.5-6.6). Among children without systemic arthritis, biologic DMARD use was most
      strongly associated with rheumatoid factor (RF)-positive polyarthritis (OR 4.3,
      95% CI 2.9-6.6), psoriatic arthritis (PsA; OR 3.0, 95% CI 2.0-4.4), and uveitis
      (OR 2.8, 95% CI 2.1-3.7). Among children with systemic arthritis, 160 (65%) ever
      received a biologic DMARD; tumor necrosis factor inhibitor use was associated
      with polyarthritis (OR 2.5, 95% CI 3.8-16), while interleukin 1 inhibitor use was
      not. CONCLUSION: About three-quarters of all children with JIA in the CARRA
      Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and
      their use was strongly associated with RF-positive polyarthritis, PsA, uveitis,
      and systemic arthritis.

PMID- 22859355
TI  - Antisynthetase syndrome with anti-Jo1 antibodies in 48 patients: pulmonary
      involvement predicts disease-modifying antirheumatic drug use.
AB  - OBJECTIVE: To analyze the characteristics, outcomes, and predictive factors of
      disease-modifying antirheumatic drug (DMARD) use in 48 patients with
      antisynthetase syndrome [characterized by myositis, interstitial lung disease
      (ILD), arthritis, Raynaud's phenomenon (RP), and/or mechanic's hands] and the
      presence of anti-histidyl-transfer RNA synthetase (anti-Jo1) autoantibodies.
      METHODS: Forty-eight patients (33 women, 15 men) who were anti-Jo1-positive
      referred to one center between 1998 and 2008 were analyzed retrospectively.
      RESULTS: The median age of disease onset was 43 years [interquartile range (IQR)
      33-53 yrs]. The median followup was 5 years (IQR 2-8 yrs). At diagnosis, 81% of
      patients presented with myositis, 80% ILD, 77% arthralgia, 48% RP, and 21%
      mechanic's hands. During the followup, 14 patients (29%) had no need for DMARD,
      while 34 (71%) required DMARD. Patients with mechanic's hands (p=0.02) and higher
      creatine phosphokinase at diagnosis (median 6070 IU/l vs 1121 IU/l; p=0.002) were
      more likely to need DMARD. ILD, noted on computed tomography scan by a
      nonspecific interstitial pneumonia score, was lower in the group of patients with
      no DMARD need (4 vs 7; p=0.04). Twenty patients (44%) presented with a pulmonary
      aggravation (worsening of radiologic score of ILD and/or pulmonary function test
      results) leading to DMARD use. Nonspecific interstitial pneumonia score (7 vs 5;
      p=0.05) and total lung volume (57.5% vs 70%; p=0.02) values predicted pulmonary
      aggravation. CONCLUSION: Our study outlines the burden of chest involvement for
      the prognosis of antisynthetase syndrome in terms of patients' requirement for
      DMARD therapy.

PMID- 22859357
TI  - Efficacy and tolerability of celecoxib in the treatment of acute gouty arthritis:
      a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the analgesic efficacy of high-dose celecoxib in the
      treatment of moderate to extreme pain and inflammation associated with acute
      gouty arthritis. METHODS: A multinational, randomized, double-blind, double
      dummy, active-controlled trial was done with patients (aged>=18 years) with acute
      gouty monoarthritis or oligoarthritis (onset of pain<=48 h before enrollment).
      Patients were treated for 8 days with 1 week followup and were randomized 1:1:1:1
      to receive celecoxib 50 mg bid, celecoxib 400 mg (followed by 200 mg later on Day
      1 and then 200 mg bid for 7 days), celecoxib 800 mg (followed by 400 mg later on
      Day 1 and then 400 mg bid for 7 days), or indomethacin 50 mg tid. RESULTS: Of 443
      patients screened, 402 were randomized and 400 received treatment. Baseline
      demographics were comparable among treatments. Patients receiving high-dose
      celecoxib (800/400 mg) experienced a significantly greater reduction in pain
      intensity on Day 2 compared with low-dose celecoxib 50 mg bid [least squares (LS)
      mean difference -0.46; p=0.0014]. For high-dose celecoxib 800/400 mg, the change
      in pain scores from baseline to Day 2 was comparable with indomethacin 50 mg tid
      (LS mean difference 0.11; p=0.4331). There were significant differences in
      adverse events when the combined celecoxib groups (29.5%) were compared with
      patients taking indomethacin (43.1%; p=0.0116). There was no change in median
      serum creatinine levels for any treatment. There were more discontinuations due
      to adverse events (8.8% vs 3%; p=0.0147) with indomethacin than with the combined
      celecoxib groups. CONCLUSION: High-dose celecoxib (800/400 mg) was significantly
      more effective than low-dose celecoxib (50 mg bid) and comparable to indomethacin
      in the treatment of moderate to extreme pain in patients with acute gouty
      arthritis. Further, celecoxib was well tolerated.

PMID- 22859356
TI  - Increased risk of systemic lupus erythematosus in 29,000 patients with biopsy
      verified celiac disease.
AB  - OBJECTIVE: To investigate a possible association between celiac disease (CD) and
      systemic lupus erythematosus (SLE). Case series have indicated a possible
      association, but population-based studies are lacking. METHODS: We compared the
      risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh
      3) from Sweden's 28 pathology departments with that in 144,352 matched
      individuals from the general population identified through the Swedish Total
      Population Register. SLE was defined as having at least 2 records of SLE in the
      Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR)
      for SLE. RESULTS: During followup, 54 individuals with CD had an incident SLE.
      This corresponded to an HR of 3.49 (95% CI 2.48-4.90), with an absolute risk of
      17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of
      followup, the HR for SLE was 2.54 (95% CI 1.57-4.10). While SLE was predominantly
      female, we found similar risk estimates in men and women. When we restricted our
      outcome to individuals who also had a dispensation for a medication used in SLE,
      the HR was 2.43 (95% CI 1.22-4.87). The HR for having 2 records of SLE diagnoses,
      out of which at least 1 had occurred in a department of rheumatology,
      nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97
      4.17). CONCLUSION: Individuals with CD were at a 3-fold increased risk of SLE
      compared to the general population. Although this excess risk remained more than
      5 years after CD diagnosis, absolute risks were low.

PMID- 22859358
TI  - Magnetic resonance arthrography of lesser metatarsophalangeal joints in patients
      with rheumatoid arthritis: relationship to clinical, biomechanical, and
      radiographic variables.
AB  - OBJECTIVE: Our exploratory study of painful lesser metatarsophalangeal (MTP)
      joints in patients with rheumatoid arthritis (RA) primarily aimed to compare the
      clinical, biomechanical, and plain radiography findings with magnetic resonance
      (MR) arthrography findings. Our secondary aim was to compare standard unenhanced
      MR with MR arthrography in imaging the lesser MTP joints in RA. METHODS: In 15
      patients with RA, the more symptomatic forefoot was imaged using 3T MR imaging.
      Proton density fat-suppressed images were acquired through the lesser MTP joints
      prior to arthrography. Under ultrasound guidance, contrast agent was injected
      into 2 lesser MTP joints. T1-weighted fat-suppressed sequences were subsequently
      acquired. The MR images were read by 2 musculoskeletal radiologists and consensus
      was reached. Spearman's correlation coefficient was used to assess the
      association between abnormalities seen on MR arthrography and the clinical,
      biomechanical, and plain radiography findings. RESULTS: MR arthrography
      demonstrated pathology at 18 of 28 lesser MTP joints (64%) examined in patients
      with RA. MR arthrography abnormalities were associated with RA disease duration,
      forefoot deformity, Larsen score, subluxation, and peak plantar pressure.
      Unenhanced MR had a sensitivity of 78% and specificity of 90% for detecting
      pathology compared to MR arthrography. CONCLUSION: Capsule and plantar plate
      pathology occurs in the painful forefoot of patients with RA and is associated
      with features of disease and deformity at the lesser MTP joints. Compared with MR
      arthrography, standard MR imaging was highly specific and moderately sensitive
      for diagnosing lesser MTP joint pathology in patients with RA.

PMID- 22859359
TI  - ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to
      methotrexate in juvenile idiopathic arthritis.
AB  - OBJECTIVE: Although methotrexate (MTX) is the most widely prescribed drug in
      juvenile idiopathic arthritis (JIA), 30% of patients fail to respond to it. To
      individualize treatment strategies, the genetic determinants of response to MTX
      should be identified. METHODS: A cohort of 287 patients with JIA treated with MTX
      was studied longitudinally over the first year of treatment. MTX response was
      defined as the American College of Rheumatology pediatric 70 criteria (ACRped70).
      We genotyped 21 single-nucleotide polymorphisms in 13 genes related to MTX
      polyglutamylation and to cellular MTX uptake and efflux. Potential associations
      between ACRped70 and genotypes were analyzed in a multivariate model and
      corrected for these 3 covariates: disease duration prior to MTX treatment,
      physician's global assessment of disease activity at baseline, and MTX dose at
      all study visits. RESULTS: MTX response was more often achieved by patients
      variant for the adenosine triphosphate-binding cassette transporter B1 (ABCB1)
      gene polymorphism rs1045642 (OR 3.80, 95% CI 1.70-8.47, p = 0.001) and patients
      variant for the ABCC3 gene polymorphism rs4793665 (OR 3.10, 95% CI 1.49-6.41, p =
      0.002) than by patients with other genotypes. Patients variant for the solute
      carrier 19A1 (SLC19A1) gene polymorphism rs1051266 were less likely to respond to
      MTX (OR 0.25, 95% CI 0.09-0.72, p = 0.011). CONCLUSION: ABCB1 rs1045642, ABCC3
      rs4793665, and SLC19A1 rs1051266 polymorphisms were associated with response to
      MTX in 287 patients with JIA studied longitudinally. Upon validation of our
      results in other JIA cohorts, these genetic determinants may help to
      individualize treatment strategies by predicting clinical response to MTX.

PMID- 22859360
TI  - Initial diagnosis of lumbar disc herniation is associated with a delay in
      diagnosis of ankylosing spondylitis.
AB  - OBJECTIVE: There is often a considerable delay in diagnosis of ankylosing
      spondylitis (AS). In this multicenter study, we analyzed the delay and possible
      associated factors, including an initial diagnosis of lumbar disc herniation
      (LDH), which we frequently encounter in daily clinical practice. METHODS: The
      study included 393 consecutive patients [258 men (65.6%), mean age 39.3 +/- 10.8
      yrs] with AS according to the modified New York criteria. Face-to-face interviews
      were done using a structured questionnaire, addressing all the potentially
      relevant factors. RESULTS: The mean diagnostic delay was 8.1 +/- 8.6 years in the
      whole study population. The shortest delay was observed when rheumatologists were
      the first physicians consulted (2.9 +/- 5.3 yrs). An initial diagnosis of LDH was
      reported by 33% of the patients. The diagnostic delays in patients with an
      initial diagnosis of LDH and those without were 9.1 +/- 8.5 years and 6.2 +/- 7.4
      years, respectively (p = 0.002). In a regression model, predictive factors for
      delay in diagnosis were age at onset of spondyloarthritic symptoms, back pain,
      education level, prior diagnosis of LDH, and surgical history for LDH.
      CONCLUSION: These results indicate the need to increase awareness of the concept
      of axial spondyloarthritis among specialists who might be the first physicians
      consulted by patients with AS for their back pain. There is also a need to
      develop strategies for early referral of such patients to rheumatologists.

PMID- 22859361
TI  - Psoriatic arthritis in Canadian clinical practice: the PsA assessment in
      rheumatology.
AB  - OBJECTIVE: We aimed to determine disease severity and treatment of patients with
      psoriatic arthritis (PsA) in rheumatology practices in Canada through the PsA
      Assessment in Rheumatology (PAIR) study. METHODS: Rheumatologists who were
      members of the Canadian Rheumatology Association were asked to complete a form
      for each patient addressing demographic questions, history, clinical examination,
      and patient-reported outcomes. Results were compared with a cohort seen in a PsA
      clinic during the same period. RESULTS: From across Canada, 22 rheumatologists
      from 5 provinces submitted information about 233 consecutive patients with PsA
      [145 men (62.2%), 88 women (37.8%), mean age 53.2 yrs (+/-12.7), 88.4% disease
      duration>2 yrs]. A majority (80.7%) fulfilled ClASsification for Psoriatic
      ARthritis (CASPAR) criteria, and 30% had taken no disease-modifying antirheumatic
      drugs. Clinical joint damage was documented in 60% of the patients, active skin
      disease in 70%, and nail lesions in 32%. Only 22% were rated as having moderate
      to high disease activity, while 52% were rated as low disease activity and 26%
      were deemed in remission. The decision was based on joint counts, patient global
      assessment, physician global assessment, and acute-phase reactants. Twenty-seven
      percent of the patients were to have their medications changed based on the
      current visit, the majority for inadequate response to medications. Patients in
      the PAIR cohort had more inflamed joints but similar damage to those in the PsA
      clinic. CONCLUSION: Patients with PsA seen in regular rheumatology practice
      fulfill CASPAR criteria, have active disease, and more than half have joint
      damage. The majority have low activity or are in remission.

PMID- 22859362
TI  - Evaluation of antigen detection tests, microscopy, and polymerase chain reaction
      for diagnosis of malaria in peripheral blood in asymptomatic pregnant women in
      Nanoro, Burkina Faso.
AB  - Rapid diagnostics tests (RDTs) detect malaria specific antigen(s) in the
      circulation, even when parasites are sequestered in the placenta and not visible
      by microscopy. However, research on their diagnostic accuracy during pregnancy is
      limited. Pregnant women (n = 418) were screened for malaria during routine
      antenatal care by using two RDTs that detect histidine-rich protein 2 (HRP2) or
      Plasmodium lactate dehydrogenase, and enzyme-linked immunosorbent assays with
      antibodies that detect dihydrofolate reductase-thymidylate synthase or heme
      detoxification protein, and compared with real-time polymerase chain reaction (RT
      PCR) and microscopy for evaluation of their diagnostic accuracy. Prevalence of
      malaria infection was high (53% by PCR). The RT-PCR and the HRP2 RDT detected
      most cases of malaria during pregnancy, whereas microscopy, the Plasmodium
      lactate dehydrogenase RDT, and enzyme-linked immunosorbent assays for
      dihydrofolate reductase-thymidylate synthase and heme-detoxification protein
      antibodies did not detect several low-density infections. Therefore, the HRP2 RDT
      could be a useful tool in high-transmission areas for diagnosis of malaria in
      asymptomatic pregnant women.

PMID- 22859363
TI  - Strategic planning processes and financial performance among hospitals in
      Lebanon.
AB  - BACKGROUND: Strategic planning has been presented as a valuable management tool.
      However, evidence of its deployment in healthcare and its effect on
      organizational performance is limited in low-income and middle-income countries
      (LMICs). The study aimed to explore the use of strategic planning processes in
      Lebanese hospitals and to investigate its association with financial performance.
      METHODS: The study comprised 79 hospitals and assessed occupancy rate (OR) and
      revenue-per-bed (RPB) as performance measures. The strategic planning process
      included six domains: having a plan, plan development, plan implementation,
      responsibility of planning activities, governing board involvement, and
      physicians' involvement. RESULTS: Approximately 90% of hospitals have strategic
      plans that are moderately developed (mean score of 4.9 on a 1-7 scale) and
      implemented (score of 4.8). In 46% of the hospitals, the CEO has the
      responsibility for the plan. The level of governing board involvement in the
      process is moderate to high (score of 5.1), whereas physician involvement is
      lower (score of 4.1). The OR and RPB amounted to respectively 70% and 59 304
      among hospitals with a strategic plan as compared with 62% and 33 564 for those
      lacking such a plan. No statistical association between having a strategic plan
      and either of the two measures was detected. However, the findings revealed that
      among hospitals that had a strategic plan, higher implementation levels were
      associated with lower OR (p < 0.05). CONCLUSIONS: In an LMIC healthcare
      environment characterized by resource limitation, complexity, and political and
      economic volatility, flexibility rather than rigid plans allow organizations to
      better cope with environmental turbulence.

PMID- 22859364
TI  - Altered colorectal afferent function associated with TNBS-induced visceral
      hypersensitivity in mice.
AB  - Inflammation of the distal bowel is often associated with abdominal pain and
      hypersensitivity, but whether and which colorectal afferents contribute to the
      hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene
      sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity
      following intracolonic TNBS and associated changes in colorectum and afferent
      functions. C57BL/6 mice were treated intracolonically with TNBS or saline.
      Visceromotor responses to colorectal distension (15-60 mmHg) were recorded over 8
      wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or
      saline, colorectal inflammation was assessed by myeloperoxidase assay and
      immunohistological staining. In vitro single-fiber recordings were conducted on
      both TNBS and saline-treated mice to assess colorectal afferent function. Mice
      exhibited significant colorectal hypersensitivity through day 14 after TNBS
      treatment that resolved by day 28 with no resensitization through day 56. TNBS
      induced a neutrophil- and macrophage-based colorectal inflammation as well as
      loss of nerve fibers, all of which resolved by days 14-28. Single-fiber
      recordings revealed a net increase in afferent drive from stretch-sensitive
      colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically
      insensitive afferents (MIAs) at days 14-28. Intracolonic TNBS-induced colorectal
      inflammation was associated with the development and recovery of hypersensitivity
      in mice, which correlated with a transient increase and recovery of sensitization
      of stretch-sensitive colorectal afferents and MIAs. These results indicate that
      the development and maintenance of colorectal hypersensitivity following
      inflammation are mediated by peripheral drive from stretch-sensitive colorectal
      afferents and a potential contribution from MIAs.

PMID- 22859365
TI  - Luminal hypertonicity and acidity modulate colorectal afferents and induce
      persistent visceral hypersensitivity.
AB  - Carbohydrate malabsorption such as in lactose intolerance or enteric infection
      causes symptoms that include abdominal pain. Because this digestive disorder
      increases intracolonic osmolarity and acidity by accumulation of undigested
      carbohydrates and fermented products, we tested whether these two factors
      (hypertonicity and acidity) would modulate colorectal afferents in association
      with colorectal nociception and hypersensitivity. In mouse colorectum-pelvic
      nerve preparations in vitro, afferent activities were monitored after application
      of acidic hypertonic saline (AHS; pH 6.0, 800 mosM). In other experiments, AHS
      was instilled intracolonically to mice and behavioral responses to colorectal
      distension (CRD) measured. Application of AHS in vitro excited 80% of serosal and
      42% of mechanically-insensitive colorectal afferents (MIAs), sensitizing a
      proportion of MIAs to become mechanically sensitive and reversibly inhibiting
      stretch-sensitive afferents. Acute intracolonic AHS significantly increased
      expression of the neuronal activation marker pERK in colon sensory neurons and
      augmented noxious CRD-induced behavioral responses. After three consecutive daily
      intracolonic AHS treatments, mice were hypersensitive to CRD 4-15 days after the
      first treatment. In complementary single fiber recordings in vitro, the
      proportion of serosal class afferents increased at day 4; the proportion of MIAs
      decreased, and muscular class stretch-sensitive afferents were sensitized at days
      11-15 in mice receiving AHS. These results indicate that luminal hypertonicity
      and acidity, two outcomes of carbohydrate malabsorption, can induce colorectal
      hypersensitivity to distension by altering the excitability and relative
      proportions of colorectal afferents, suggesting the potential involvement of
      these factors in the development of abdominal pain.

PMID- 22859367
TI  - From ubiquitin-proteasomal degradation to CDK1 inactivation: requirements for the
      first polar body extrusion in mouse oocytes.
AB  - Completion of the first meiotic division, manifested by extrusion of the first
      polar body (PBI), depends on proteasomal degradation of cyclin B1 and securin and
      the subsequent respective CDK1 inactivation and chromosome segregation. We aimed
      at identifying the polyubiquitin signal that mediates proteasomal action and at a
      better characterization of the role of CDK1 inactivation at this stage of
      meiosis. Microinjections of mutated ubiquitin proteins into mouse oocytes
      revealed that interference with lysine-11 polyubiquitin chains abrogated
      chromosome segregation and reduced PBI extrusion by 63% as compared to WT
      ubiquitin-injected controls. Inactivation of CDK1 in oocytes arrested at first
      metaphase by a proteasome inhibitor fully rescued PBI extrusion. However, removal
      of CDK1 inhibition failed to allow progression to the second metaphase, rather,
      inducing PBI reengulfment in 62% of the oocytes. Inhibition of either PLK1 or
      MEK1/2 during the first anaphase changed spindle dimensions. The PLK1 inhibitor
      also blocked PBI emission and prevented RhoA translocation. Our results
      identified lysine-11 rather than the canonic lysine-48 ubiquitin chains as the
      degradation signal in oocytes resuming meiosis, further disclosing that CDK1
      inactivation is necessary and sufficient for PBI emission. This information
      significantly contributes to our understanding of faulty chromosome segregation
      that may lead to aneuploidy.

PMID- 22859366
TI  - Loss of intracellular lipid binding proteins differentially impacts saturated
      fatty acid uptake and nuclear targeting in mouse hepatocytes.
AB  - The liver expresses high levels of two proteins with high affinity for long-chain
      fatty acids (LCFAs): liver fatty acid binding protein (L-FABP) and sterol carrier
      protein-2 (SCP-2). Real-time confocal microscopy of cultured primary hepatocytes
      from gene-ablated (L-FABP, SCP-2/SCP-x, and L-FABP/SCP-2/SCP-x null) mice showed
      that the loss of L-FABP reduced cellular uptake of 12-N-methyl-(7-nitrobenz-2-oxa
      1,3-diazo)-aminostearic acid (a fluorescent-saturated LCFA analog) by ~50%.
      Importantly, nuclear targeting of the LCFA was enhanced when L-FABP was
      upregulated (SCP-2/SCP-x null) but was significantly reduced when L-FABP was
      ablated (L-FABP null), thus impacting LCFA nuclear targeting. These effects were
      not associated with a net decrease in expression of key membrane proteins
      involved in LCFA or glucose transport. Since hepatic LCFA uptake and metabolism
      are closely linked to glucose uptake, the effect of glucose on L-FABP-mediated
      LCFA uptake and nuclear targeting was examined. Increasing concentrations of
      glucose decreased cellular LCFA uptake and even more extensively decreased LCFA
      nuclear targeting. Loss of L-FABP exacerbated the decrease in LCFA nuclear
      targeting, while loss of SCP-2 reduced the glucose effect, resulting in enhanced
      LCFA nuclear targeting compared with control. Simply, ablation of L-FABP
      decreases LCFA uptake and even more extensively decreases its nuclear targeting.

PMID- 22859368
TI  - The protease MT1-MMP drives a combinatorial proteolytic program in activated
      endothelial cells.
AB  - The mechanism by which proteolytic events translate into biological responses is
      not well understood. To explore the link of pericellular proteolysis to events
      relevant to capillary sprouting within the inflammatory context, we aimed at the
      identification of the collection of substrates of the protease MT1-MMP in
      endothelial tip cells induced by inflammatory stimuli. We applied quantitative
      proteomics to endothelial cells (ECs) derived from wild-type and MT1-MMP-null
      mice to identify the substrate repertoire of this protease in TNF-alpha-activated
      ECs. Bioinformatics analysis revealed a combinatorial MT1-MMP proteolytic
      program, in which combined rather than single substrate processing would
      determine biological decisions by activated ECs, including chemotaxis, cell
      motility and adhesion, and vasculature development. MT1-MMP-deficient ECs
      inefficiently processed several of these substrates (TSP1, CYR61, NID1, and
      SEM3C), validating the model. This novel concept of MT1-MMP-driven combinatorial
      proteolysis in angiogenesis might be extendable to proteolytic actions in other
      cellular contexts.

PMID- 22859369
TI  - Intrafibrillar silicification of collagen scaffolds for sustained release of stem
      cell homing chemokine in hard tissue regeneration.
AB  - Traditional bone regeneration strategies relied on supplementation of
      biomaterials constructs with stem or progenitor cells or growth factors. By
      contrast, cell homing strategies employ chemokines to mobilize stem or progenitor
      cells from host bone marrow and tissue niches to injured sites. Although silica
      based biomaterials exhibit osteogenic and angiogenic potentials, they lack cell
      homing capability. Stromal cell-derived factor-1 (SDF-1) plays a pivotal role in
      mobilization and homing of stem cells to injured tissues. In this work, we
      demonstrated that 3-dimensional collagen scaffolds infiltrated with
      intrafibrillar silica are biodegradable and highly biocompatible. They exhibit
      improved compressive stress-strain responses and toughness over nonsilicified
      collagen scaffolds. They are osteoconductive and up-regulate expressions of
      osteogenesis- and angiogenesis-related genes more significantly than
      nonsilicified collagen scaffolds. In addition, these scaffolds reversibly bind
      SDF-1alpha for sustained release of this chemokine, which exhibits in vitro cell
      homing characteristics. When implanted subcutaneously in an in vivo mouse model,
      SDF-1alpha-loaded silicified collagen scaffolds stimulate the formation of
      ectopic bone and blood capillaries within the scaffold and abrogate the need for
      cell seeding or supplementation of osteogenic and angiogenic growth factors.
      Intrafibrillar-silicified collagen scaffolds with sustained SDF-1alpha release
      represent a less costly and complex alternative to contemporary cell seeding
      approaches and provide new therapeutic options for in situ hard tissue
      regeneration.

PMID- 22859371
TI  - Double Myod and Igf2 inactivation promotes brown adipose tissue development by
      increasing Prdm16 expression.
AB  - Brown fat or brown adipose tissue (BAT), found in newborn mammals as small depots
      localized in the interscapular region, plays a prominent role in regulating
      thermogenesis perinatally. The physiological importance of functional BAT has
      been recently reasserted in human adults. Because myoblasts and adipoblasts
      emerge from a common mesodermal precursor, we investigated developmental
      determination and the reciprocal relationship between muscle and adipocyte
      commitment. Here we show that a mutant mouse defective for both Igf2 and Myod
      genes exhibits massive BAT hypertrophy compared with wild-type and single-mutant
      newborns. The increased adipocyte proliferation in BAT of double-mutant newborns
      was associated with overexpression of the brown fat-specific marker Ucp1. More
      strikingly, expression of the master key gene Prdm16 involved in the switch
      between myogenic and brown adipogenic lineages was drastically enhanced. We
      further demonstrate that concomitant Myod and Igf2 inactivation accelerates
      differentiation of a brown preadipocyte cell line and induces lipid accumulation
      and increased Ucp1 and Prdm16 expression. This in vitro approach brings
      additional support for the implication of both Myod and Igf2 in BAT development.
      These results provide the first in vivo evidence that a myogenic regulator
      together with a growth factor act simultaneously but through independent pathways
      to repress Prdm16, which opens potential therapeutic perspectives for human
      metabolic disorders.

PMID- 22859370
TI  - Defining the cellular repertoire of GPCRs identifies a profibrotic role for the
      most highly expressed receptor, protease-activated receptor 1, in cardiac
      fibroblasts.
AB  - G-protein-coupled receptors (GPCRs) have many roles in cell regulation and are
      commonly used as drug targets, but the repertoire of GPCRs expressed by
      individual cell types has not been defined. Here we use an unbiased approach,
      GPCR RT-PCR array, to define the expression of nonchemosensory GPCRs by cardiac
      fibroblasts (CFs) isolated from Rattus norvegicus. CFs were selected because of
      their importance for cardiac structure and function and their contribution to
      cardiac fibrosis, which occurs with advanced age, after acute injury (e.g.,
      myocardial infarction), and in disease states (e.g., diabetes mellitus,
      hypertension). We discovered that adult rat CFs express 190 GPCRs and that
      activation of protease-activated receptor 1 (PAR1), the most highly expressed
      receptor, raises the expression of profibrotic markers in rat CFs, resulting in a
      60% increase in collagen synthesis and conversion to a profibrogenic
      myofibroblast phenotype. We use siRNA knockdown of PAR1 (90% decrease in mRNA) to
      show that the profibrotic effects of thrombin are PAR1-dependent. These findings,
      which define the expression of GPCRs in CFs, provide a proof of principle of an
      approach to discover previously unappreciated, functionally relevant GPCRs and
      reveal a potential role for thrombin and PAR1 in wound repair and pathophysiology
      of the adult heart.

PMID- 22859373
TI  - Dual reporter approaches for identification of Cre efficacy and astrocyte
      heterogeneity.
AB  - Gene inactivation reporters are powerful tools to circumvent limitations of the
      widely used Cre/loxP system of conditional mutagenesis. With new conditional
      transgenic mouse lines expressing the enhanced cyan fluorescent protein (ECFP)
      instead of connexin43 (Cx43) after Cre-mediated recombination, we demonstrate
      dual reporter approaches to simultaneously examine astrocyte subpopulations
      expressing different connexins, identify compensatory up-regulation within gene
      families, and quantify Cre-mediated deletion at the allelic level. Analysis of a
      newly generated Cx43 knock-in ECFP mouse revealed an unexpected heterogeneity of
      Cx43-expressing astrocytes across brain areas.

PMID- 22859372
TI  - Mitochondria-localized caveolin in adaptation to cellular stress and injury.
AB  - We show here that the apposition of plasma membrane caveolae and mitochondria
      (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria
      interaction regulates adaptation to cellular stress by modulating the structure
      and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin
      specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to
      mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium,
      and respiratory function (72% increase in state 3 and 23% increase in complex IV
      activity; P<0.05), while reducing stress-induced generation of reactive oxygen
      species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide
      under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast,
      mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis
      elegans with null mutations in caveolin (60% increase free radical in Cav-2 C.
      elegans mutants; P<0.05). In human colon cancer cells, mitochondria with
      increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells
      with disrupted mitochondria-caveolin interaction have a 30% increase in stress
      response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6
      mice increases cardiac mitochondria tolerance to calcium, enhances respiratory
      function (increases of 90% state 4, 220% state 3, 88% complex IV activity;
      P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and
      apparently the transfer of caveolin between caveolae and mitochondria is thus a
      conserved cellular response that confers protection from cellular damage in a
      variety of tissues and settings.

PMID- 22859374
TI  - Docking protein Gab2 regulates mucin expression and goblet cell hyperplasia
      through TYK2/STAT6 pathway.
AB  - Goblet cell hyperplasia (GCH) and mucous hypersecretion are common pathological
      features of chronic pulmonary diseases, including asthma, chronic obstructive
      pulmonary disease (COPD), lung cancer, and cystic fibrosis. Despite numerous
      studies, the molecular basis for this condition remains elusive. Gab2 is a member
      of the Dos/Gab subfamily scaffolding molecules and plays important roles in
      regulating growth, differentiation, and inflammation. We found that an elevated
      level of Gab2 correlates with up-regulated mucus in airway epithelia from
      patients with lung cancer or COPD, suggesting the potential involvement of Gab2
      in pathological lesions in lungs. Knockdown of Gab2 in human airway epithelial
      cells in vitro decreases IL-13-induced expression of mucin genes. To address the
      in vivo role of Gab2 in lungs, Gab2-knockout (Gab2(-/-)) mice were sensitized and
      challenged with ovalbumin (OVA). Further analysis of lungs in an OVA-induced
      allergy model suggested that GCH and mucus production are remarkably reduced in
      Gab2(-/-) mice. Mechanistically, Gab2 positively regulates IL-13-induced
      activation of TYK2/STAT6 by decreasing SOCS3-mediated degradation of TYK2.
      Together, we define a novel role for Gab2 in mediating mucin gene expression and
      GCH; these findings have important implications for the pathogenesis and therapy
      of airway inflammatory diseases.

PMID- 22859375
TI  - Tomato powder impedes the development of azoxymethane-induced colorectal cancer
      in rats through suppression of COX-2 expression via NF-kappaB and regulating
      Nrf2/HO-1 pathway.
AB  - Cancer is one of the leading causes of death worldwide. Since dietary factors
      have been connected to a reduced risk of a diversity of human cancers, in this
      study we investigated the effects of tomato powder (TP) on the development of
      azoxymethane (AOM)-induced colorectal cancer in Wistar rats, and possible
      mechanism(s) by which TP shows its chemopreventive activity. Here we show that TP
      added to feed at 5% rate decreases the rate of aberrant crypt foci (ACF) and
      reduces the development of adenocarcinoma and growth of AOM-induced colorectal
      cancer in rats. In addition, we demonstrate that TP supplementation shows its
      chemopreventive activities through inhibition of cyclooxygenase-2 (COX-2)
      expression via NF-kappaB pathway and promotion of apoptosis, as well as
      regulating Nrf2/HO-1 signaling pathway in colorectal tissue of AOM-treated rats.
      Our findings identify an intimate connection between dietary supplementation of
      TP and the decreased risk of colorectal cancer in rats, and suggest that
      consumption of TP would be a natural candidate for the prevention of colorectal
      cancer in men.

PMID- 22859376
TI  - Evidence and decision making: tobacco control policy and legislation in Vietnam.
AB  - The Ministry of Health (MOH) in Vietnam is currently drafting the Tobacco Harm
      Prevention Law. The government requested the MOH to provide evidence on the
      strategies proposed in the draft law as part of its submission to the National
      Assembly. This study examines the availability and strength of evidence and its
      relationship to policy stakeholders' positions towards policy instruments
      proposed in the law. Several qualitative methods were employed including
      documentary analysis, key informant interviews, focus group discussion and a key
      stakeholders' survey. Contradictory findings were identified over the role of
      evidence. While there is high demand for local evidence, the availability and
      strength of evidence are not always aligned with stakeholders' positions with
      respect to different strategies. Stakeholders' positions are shaped by competing
      interests on the basis of their perceptions of the socioeconomic implications and
      health consequences of tobacco control. Claims of limited availability of
      evidence are often used to justify the maintenance of the status quo, a position
      that is seen to protect the state-owned tobacco industry and state revenue. Local
      evidence of the impact of tobacco on population health is argued to be 'one
      sided' and evidence of selected interventions discounted. Compelling and
      comprehensive local evidence, including those addressing economic concerns, is
      acutely needed in order to proceed with the current legislation process. For
      evidence to play a critical role, it needs to engage those ministries responsible
      for the tobacco industry itself and the economic development.

PMID- 22859379
TI  - Use of cannabis enhances attentional inhibition.
AB  - OBJECTIVE: Orienting attention to an irrelevant location hampers the response to
      subsequent targets presented at that location in relation to novel, not
      previously attended, locations. This inhibitory effect has been named inhibition
      of return. We conducted an experiment to study the temporal course of inhibition
      of return in users of cannabis. METHOD: Twenty-five cannabis users who self
      reported a regular frequency of cannabis use in joints per month, and 26 drug
      free controls participated in the study. We employed a typical inhibition of
      return task with a single cue and manipulated the time interval between the onset
      of the cue and the target (150, 350, 550, 1500, and 2550 ms). Participants were
      asked to detect the onset of the target regardless of its location. RESULTS: The
      group of cannabis users showed a significantly greater overall inhibition
      relative to the group of nonusers. Furthermore, inhibition of return appeared
      earlier (at the 350 ms cue-target interval) in the user group. CONCLUSIONS: This
      is the first study to show that attentional inhibition is enhanced in cannabis
      users. More research is needed to determine whether greater inhibition represents
      an advantage or disadvantage for visual search performance of cannabis users.

PMID- 22859380
TI  - Surgical approaches to complex vascular lesions: the use of virtual reality and
      stereoscopic analysis as a tool for resident and student education.
AB  - Virtual reality training for complex tasks has been shown to be of benefit in
      fields involving highly technical and demanding skill sets. The use of a
      stereoscopic three-dimensional (3D) virtual reality environment to teach a
      patient-specific analysis of the microsurgical treatment modalities of a complex
      basilar aneurysm is presented. Three different surgical approaches were evaluated
      in a virtual environment and then compared to elucidate the best surgical
      approach. These approaches were assessed with regard to the line-of-sight, skull
      base anatomy and visualisation of the relevant anatomy at the level of the
      basilar artery and surrounding structures. Overall, the stereoscopic 3D virtual
      reality environment with fusion of multimodality imaging affords an excellent
      teaching tool for residents and medical students to learn surgical approaches to
      vascular lesions. Future studies will assess the educational benefits of this
      modality and develop a series of metrics for student assessments.

PMID- 22859381
TI  - A mysterious visitor to the heart.

PMID- 22859382
TI  - Recurrent episodic hypoxaemic respiratory failure following a stroke.
AB  - A 68-year-old man with no cardiovascular risk factors was admitted with a stroke
      because of multiple brain infarcts in different vascular territories. He required
      mechanical ventilation for hypoxia as a result of aspiration pneumonia.
      Subsequent recovery was hindered by episodic, unexplained hypoxia. Investigations
      excluded pulmonary embolism, pulmonary hypertension and severe lung diseases.
      Transthoracic echocardiography (TTE) with saline bubble contrast showed mild,
      delayed, right-to-left shunting, thought to represent an insignificant,
      intrapulmonary, non-cardiac shunt. Hypoxic episodes worsened, requiring admission
      from community rehabilitation hospital to our centre and another period of
      mechanical ventilation. Elevated alveolar-arterial gradients indicated a non
      hypoventilatory cause. Repeat TTE bubble contrast study and transoesophageal
      echocardiography (TOE) demonstrated a patent foramen ovale (PFO) with large shunt
      potential, associated with an aneurysmal interatrial septum. This provided a
      unifying explanation for cryptogenic stroke and recurrent hypoxaemia. After
      percutaneous PFO closure hypoxic episodes ceased and he returned successfully to
      rehabilitation.

PMID- 22859383
TI  - Topiramate-induced refractive change and angle closure glaucoma and its
      ultrasound bimicroscopy findings.
AB  - Topiramate, a sulpha-based medication used in the treatment of migraine, has been
      documented as causing choroidal effusions, transient myopia and acute secondary
      angle closure glaucoma. We would like to report a case demonstrating these
      adverse effects and underscore the utility of ultrasound biomicroscopy in
      diagnosis and management.

PMID- 22859384
TI  - Giant cell phlebitis: a potentially lethal clinical entity.
AB  - An 83-year-old woman presented to us with a 4-week history of general malaise,
      subjective fever and lower abdominal pain. Despite the intravenous infusion of
      antibiotics, her blood results and physical condition worsened, resulting in her
      sudden death. Autopsy study revealed that the medium-sized veins of the mesentery
      were infiltrated by eosinophil granulocytes, lymphocytes, macrophages and
      multinucleated giant cells; however, the arteries were not involved.
      Microscopically, venous giant cell infiltration was observed in the
      gastrointestinal tract, bladder, retroperitoneal tissues and myocardium. The
      final diagnosis was giant cell phlebitis, a rare disease of unknown aetiology.
      This case demonstrates for the first time that giant cell phlebitis involving
      extra-abdominal organs, including hearts, can cause serious morbidity.

PMID- 22859385
TI  - High-speed tracking of murine cardiac stem cells by harmonic nanodoublers.
AB  - Potassium niobate nonlinear nanoparticles are used for the first time to monitor
      the evolution of embryonic stem cells (ESC) by second harmonic microscopy. These
      particles feature the complete absence of photo-bleaching and unlimited
      excitation wavelength flexibility. The potential of this approach is made evident
      for tissue-regeneration studies and applications, by capturing a high-speed movie
      of ESC-derived cardiomyocytes autonomously beating within a cluster. Time
      resolved data are analyzed to retrieve 3D information of the contraction pattern
      at the cellular level.

PMID- 22859386
TI  - Full solution-processed synthesis of all metal oxide-based tree-like
      heterostructures on fluorine-doped tin oxide for water splitting.
AB  - Well-ordered tree-like functional heterostructures, composed of the
      environmentally friendly oxides ZnO, TiO(2) , and CuO, on a fluorine-doped tin
      oxide substrate are realized by a practical, cost-effective, solution-processable
      strategy. The heterostructures are demonstrated to be an efficient light
      harvesting medium in a photo-electrochemical cell to split water for hydrogen-gas
      generation, and the developed strategy provides a highly promising, cheap, green
      way to fabricate multifunctional hierarchically branched structures for many
      potential applications.

PMID- 22859387
TI  - Not all older adults have insight into their driving abilities: evidence from an
      on-road assessment and implications for policy.
AB  - PURPOSE: To compare self-reported driving ability with objective measures of on
      road driving performance in a large cohort of older drivers. METHODS: Two hundred
      and seventy community-living adults aged 70-88 years recruited via the electoral
      roll completed a standardized assessment of on-road driving performance and
      questionnaires determining perceptions of their own driving ability, confidence,
      and driving difficulties. Retrospective self-reported crash data over the
      previous 5 years were recorded. RESULTS: Participants reported difficulty with
      only selected driving situations, including driving into the sun, in unfamiliar
      areas, in wet conditions, and at night or dusk. The majority of participants
      rated their own driving as good to excellent. Of the 47 (17%) drivers who were
      rated as potentially unsafe to drive, 66% rated their own driving as good to
      excellent. Drivers who made critical errors, where the driving instructor had to
      take control of the vehicle, had no lower self-rating of driving ability than the
      rest of the group. The discrepancy in self-perceptions of driving ability and
      participants' safety rating on the on-road assessment was significantly
      associated with self-reported retrospective crash rates, where those drivers who
      displayed greater overconfidence in their own driving were significantly more
      likely to report a crash. CONCLUSIONS: This study demonstrates that older drivers
      with the greatest mismatch between actual and self-rated driving ability pose the
      greatest risk to road safety. Therefore, licensing authorities should not assume
      that when older individuals' driving abilities begin to decline they will
      necessarily be aware of these changes and adopt appropriate compensatory driving
      behaviors; rather, it is essential that evidence-based assessments are adopted.

PMID- 22859388
TI  - Leptin, mild cognitive impairment, and dementia among elderly women.
AB  - BACKGROUND: The association between obesity and dementia has been inconsistent,
      possibly due to changes in body composition often seen in old age. Leptin may be
      associated with better cognitive function. However, neuroprotection may be
      inhibited among obese subjects possibly due to leptin resistance. We sought to
      determine (i) if leptin is associated with risk of dementia or mild cognitive
      impairment (MCI) in a cohort of very old women, (ii) if this association is
      modified by obesity, and (iii) if leptin is a stronger risk factor compared with
      traditional anthropometric measures. METHODS: We studied 579 older women (mean
      age 82.6 years) from the ongoing prospective cohort Study of Osteoporotic
      Fractures, who were dementia-free at year-16 examination (our study baseline).
      Leptin (ng/mL) was measured using year-16 frozen serum, and anthropometric
      measures were collected during the same visit. Diagnosis of dementia/MCI was
      determined at year-20 examination. RESULTS: There was evidence for a
      multiplicative interaction between log leptin and categorical body mass index (p
      = .03). Among women with body mass index <25kg/m(2) (n = 190), 1SD difference in
      log leptin (0.91ng/mL) was associated with 32% lower odds of dementia/MCI (OR =
      .68; 95% CI = .46, .99), after adjustment. The association was not significant
      among women with body mass index >=25kg/m(2) (n = 377). Traditional
      anthropometric measures such as weight, height, and body mass index were not
      associated with dementia/MCI. CONCLUSIONS: In this cohort of very old women,
      higher serum leptin was prospectively associated with lower odds of dementia/MCI
      in women with normal body mass index, but not in overweight or obese women.
      Leptin may be a better predictor of dementia/MCI than traditional anthropometric
      measures.

PMID- 22859389
TI  - Muscle protein synthetic responses to exercise: effects of age, volume, and
      intensity.
AB  - We explored the relationships between resistance exercise volume/intensity and
      muscle myofibrillar protein synthetic (MPS) responses in young and older men. In
      a crossover design, four groups of six young (24+/-6 years) and older (70+/-5
      years) men performed two volumes of resistance exercise: either 40% one
      repetition maximum (1RM) (3 * 14, then 6 * 14 repetitions) or 75% 1RM (3 * 8,
      then 6 * 8 repetitions), such that at the same volume, work was identical between
      intensities. Muscle biopsies were taken 0, 1, 2, and 4hours after exercise to
      measure MPS via myofibrillar bound [1,2-(13)C(2)]leucine and indices of mammalian
      target of rapamycin signaling by immunoblotting. In younger men, doubling
      exercise volume produced limited added effects, whereas in older men, it resulted
      in greater MPS and p70S6 kinase (p70S6K(Thr389)) phosphorylation at both
      intensities, that is, MPS area under the curve: 75% (1* volume: 0.07+/-0.01 vs 2*
      volume: 0.14% +/- 0.02% protein synthesized/4hours (p < .001). Doubling exercise
      volume is a valid strategy to maximize postexercise MPS in ageing.

PMID- 22859390
TI  - Insulin resistance and aging: a cause or a protective response?

PMID- 22859391
TI  - Expression of D-type cyclins in AL amyloidosis plasma cells.

PMID- 22859392
TI  - Diagnostic accuracy of icteric index to detect abnormal total bilirubin values.
AB  - AIMS: Total bilirubin tests are individually inexpensive but can result in huge
      costs to healthcare systems worldwide, because they are very commonly requested.
      The main objective of this study was to evaluate the diagnostic accuracy of the
      icteric index, a test with zero reagent cost, as a preliminary biomarker to
      decide when total bilirubin measurement is necessary. METHODS: We retrospectively
      reviewed all the requested total bilirubin values and their corresponding icteric
      index results in a 2-year period (2010-11). Receiver operating characteristic
      (ROC) curve analysis was used to determine the optimal icteric index cut-off
      value to discriminate between normal and abnormal bilirubin values (>20.5
      MUmol/l; >1.2 mg/dl). RESULTS: The study included total bilirubin and icteric
      index results of 100,207 patients. The ROC curve analysis suggested 34.2 MUmol/l
      (2 mg/dl) as the optimal icteric index threshold to identify abnormal bilirubin
      values. The area under the curve was 0.981. Regardless of the patient population
      studied (primary care, hospital and different individual hospital departments),
      sensitivity was greater than 94% and specificity was over 98%. Likelihood ratio
      values provided strong evidence that total bilirubin is less than 20.5 MUmol/l
      (<1.2 mg/dl) when the icteric index is less than 34.2 MUmol/l (<2 mg/dl).
      CONCLUSIONS: This study supports the use of the icteric index to identify
      patients with abnormal total bilirubin values. Considerable economic savings can
      be achieved if this strategy is applied on a clinical daily basis. Its
      implementation and report should be discussed and planned by laboratory
      professionals together with requesting physicians.

PMID- 22859393
TI  - A fluorescence-based assay for monitoring clinical drug resistance.
AB  - BACKGROUND AND AIMS: Multidrug resistance (MDR) limits effectiveness in treating
      malignancy by modifying internalisation and/or externalisation of drugs through
      cancer cell membranes. In this study we describe an assay to monitor patients'
      responses to chemotherapy. METHODS: The assay is based on the fluorescent
      properties of doxorubicin alone as well as in combination with methotrexate,
      vinblastine, doxorubicin and cisplatin (MVAC). The slide-based cell imaging
      technique was first optimised using a panel of breast and urothelial cancer cell
      lines and then extended to fine needle breast aspiration biopsy and urine
      cytology. RESULTS: The drug fluorescence behaviour observed on smears of clinical
      specimens is identical to that obtained using fixed cultured cells. The
      fluorescence of sensitive cells to chemotherapy is mainly localised in the
      nucleus, whereas resistant cells show a weak fluorescence signal localised in the
      cytoplasm. The difference in terms of fluorescence intensity is also highlighted
      through fluorescence spectra. CONCLUSIONS: The results suggest that the assay
      provides clinically valuable information in predicting responses to doxorubicin
      and/or MVAC therapy. Originally set up on a confocal microscope, the assay was
      also effective using a standard epifluorescence microscope; as such it is
      technically simple, reliable and inexpensive.

PMID- 22859394
TI  - Prognostic and predictive significance of proliferation in 867 colorectal
      cancers.
AB  - AIM: Recently, the Oncotype DX recurrence score, which measures a gene expression
      signature including markers of tumour proliferation, was validated as a
      prognostic signature in colorectal cancer. This study aimed to evaluate whether
      the Ki67 proliferation index can provide similar prognostic and predictive
      information. METHODS: Tissue microarrays were constructed from triplicate cores
      of colorectal cancer. Immunohistochemistry for Ki67 was performed with the SP6
      antibody and the percentage of positive tumour cells scored. Prognostic
      significance was evaluated in 867 cancers (601 events) using Cox proportional
      hazards models. RESULTS: The Ki67 labelling index, divided at the median, was not
      a statistically or clinically significant prognostic factor in univariate
      analyses of 5-year overall survival (HR 0.98, 95% CI 0.84 to 1.15, p=0.84).
      Multivariate analyses were similarly non-significant. However, in Dukes' stage C
      patients, the high Ki67 subgroup derived a greater 5-year overall survival
      benefit from chemotherapy (HR 0.32, 95% CI 0.21 to 0.51, p<0.0001) than the low
      subgroup (HR 0.57, 95% CI 0.37 to 0.89, p=0.011). CONCLUSIONS: The Ki67
      proliferation index is not a useful prognostic factor in colorectal cancer, but
      deserves further evaluation as a predictive factor for the incremental benefit
      derived from adjuvant chemotherapy.

PMID- 22859395
TI  - Point-of-care monitoring of vitamin K-antagonists: validation of CoaguChek XS
      test strips with International Standard thromboplastin.
AB  - AIMS: Many patients treated with vitamin K-antagonists (VKA) use point-of-care
      (POC) whole blood coagulometers for self-testing. The majority of patients in the
      Netherlands use one type of POC coagulometer, that is, the CoaguChek XS. Each new
      lot of test strips for the CoaguChek XS is validated by a group of collaborating
      thrombosis centres. We assessed the International Normalised Ratio (INR)
      differences between each of 51 new lots of test strips and the International
      Standard for thromboplastin rTF/95 or its successor rTF/09. METHODS: Each year, a
      particular lot of CoaguChek XS test strips was used as reference lot. The
      reference lot was validated by comparison to the International Standard, yielding
      a relationship between the reference lot INR and International Standard INR.
      Successive lots of test strips were compared to the reference lot by three
      centres using 19-29 capillary blood samples obtained from VKA-treated patients.
      Each patient provided two blood drops from the same finger prick, one for the
      reference lot strip and one for the new lot. RESULTS: The mean INR differences
      between each lot and the International Standard varied between -8% and +4%. The
      mean absolute values of the relative differences varied between 2.4% and 8.1%.
      There were small but clinically unimportant differences in INR between the first
      and second drop of blood. CONCLUSIONS: Accuracy of CoaguChek XS INR
      determinations can be assessed by a group of collaborating centres using a
      limited number of capillary blood samples. As the mean INR differences with the
      International Standard were smaller than 10%, the lots were approved for use by
      the Netherlands Thrombosis Services.

PMID- 22859396
TI  - Prognostic impact of beta-2-microglobulin expression in colorectal cancers
      stratified by mismatch repair status.
AB  - BACKGROUND: beta-2-microglobulin (B2M) is essential for antigen presentation, yet
      may also possess proto-oncogenic properties. AIM: To determine the prognostic
      impact of B2M in patients with mismatch repair (MMR) proficient and deficient
      colorectal cancer (CRC) and to investigate whether this effect on outcome is
      dependent on the local immune response. METHODS: B2M protein expression and
      tumour-infiltrating immune cells (CD3, CD16, CD163, CD20, CD4, CD45RO, CD56,
      CD68, CD8, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1, TIA-1) were
      evaluated in a well characterised tissue microarray of 408 CRCs. The predictive
      value for clinicopathological features and the prognostic significance of B2M
      expression were analysed, stratified by MMR status and the immunohistological
      characteristics of immune cell infiltrates. RESULTS: Interobserver agreement for
      B2M staining was high (intra-class correlation coefficient=0.91). Complete B2M
      loss was more frequent in MMR-deficient (19.4%) compared to MMR-proficient (7.1%)
      tumours (p<0.001). In MMR-deficient cases, B2M loss predicted rare local
      recurrence (p=0.034), infrequent nodal-positivity (p=0.035), absence of distant
      metastasis (p=0.048; sensitivity=100%) and a trend towards favourable survival
      (p=0.124) independent of immune infiltrates. No associations between B2M and
      clinicopathological features were observed in MMR-proficient cases. CONCLUSIONS:
      Our data show for the first time that absence of B2M protein expression
      identifies MMR-deficient cancers with a favourable clinical course and absence of
      metastatic disease. Validation of B2M protein expression for sub-classification
      of MMR-deficient CRC is recommended for future clinical trials.

PMID- 22859397
TI  - Pathological grading of regression: an International Study Group perspective.

PMID- 22859398
TI  - Variation in IL10 and other genes involved in the immune response and in
      oxidation and prostate cancer recurrence.
AB  - BACKGROUND: To evaluate the association of variation in genes involved in immune
      response, including IL10, production and detoxification of reactive oxygen
      species, and repair of oxidative DNA damage with risk of recurrence after surgery
      for localized prostate cancer. METHODS: We conducted a nested case-control study
      of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence
      cases and 484 controls were matched on age, race, and pathologic stage and grade.
      Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We
      genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1,
      GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3,
      TLR4, and TNF and tagging SNPs in IL10, CRP, GSR, IL1RN, IL6, NOS2, and NOS3. We
      used conditional logistic regression to estimate OR and 95% confidence intervals
      (CI). RESULTS: The minor allele (A) in IL10 rs1800872, known to produce less
      interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR =
      1.76, 95% CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce
      more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI:
      0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and
      IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with
      recurrence. CONCLUSION: Variation in IL10, CRP, GSTP1, IL1B, and NOS2 was
      associated with prostate cancer recurrence independent of pathologic prognostic
      factors. IMPACT: This study supports that genetic variation in immune response
      and oxidation influence prostate cancer recurrence risk and suggests genetic
      variation in these pathways may inform prognosis.

PMID- 22859401
TI  - Associations of lifestyle factors and anthropometric measures with repeat PSA
      levels during active surveillance/monitoring.
AB  - BACKGROUND: Assessment of prostate-specific antigen increase with time (PSA
      growth) is a fundamental component of active surveillance among men with
      localized prostate cancer. Factors that influence PSA growth, however, are
      unclear. We evaluated associations of anthropometric and lifestyle factors with
      age-related PSA growth. METHODS: Repeat PSA measures from 404 men, aged 50 to 69
      years, with localized prostate cancer undergoing active monitoring were obtained.
      From log(PSA) measures, age-specific multilevel mixed effect linear models were
      developed to predict PSA at age 50 years and yearly increase in postdiagnosis
      PSA. Baseline anthropometric measures, alcohol consumption, occupational class,
      smoking status, and physical activity were added to the model as covariates.
      RESULTS: The median number of repeat PSAs was 13 (range, 2-40), and the mean
      duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA
      growth in men with localized prostate cancer estimated a mean PSA at age 50 of
      3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of
      8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit
      increase in weighted exercise score (95% CI: -3.3 to -0.8), 5.3% lower per 5 cm
      increase in height (95% CI: -9.4 to -1.1), and 24.5% higher (95% CI: 4.0 to 49.1)
      in current smokers than never smokers. Similar associations with PSA growth were
      seen. CONCLUSION: Smoking and exercise are modifiable lifestyle factors that may
      be associated with PSA levels in men with localized prostate cancer undergoing
      active monitoring/surveillance. IMPACT: These factors may be useful in
      understanding etiology of progression.

PMID- 22859400
TI  - Age-associated gene expression in normal breast tissue mirrors qualitative age-at
      incidence patterns for breast cancer.
AB  - BACKGROUND: Age is the strongest breast cancer risk factor, with overall breast
      cancer risk increasing steadily beginning at approximately 30 years of age.
      However, while breast cancer risk is lower among younger women, young women's
      breast cancer may be more aggressive. Although, several genomic and epidemiologic
      studies have shown higher prevalence of aggressive, estrogen-receptor negative
      breast cancer in younger women, the age-related gene expression that predisposes
      to these tumors is poorly understood. Characterizing age-related patterns of gene
      expression in normal breast tissues may provide insights on etiology of distinct
      breast cancer subtypes that arise from these tissues. METHODS: To identify age
      related changes in normal breast tissue, 96 tissue specimens from patients with
      reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression
      microarray. RESULTS: Significant associations between gene expression levels and
      age were identified for 802 probes (481 increased, 321 decreased with increasing
      age). Enriched functions included "aging of cells," "shape change," and
      "chemotaxis," and enriched pathways included Wnt/beta-catenin signaling, Ephrin
      receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to
      publicly available tumor datasets, the age-associated pathways defined two groups
      of tumors with distinct survival. CONCLUSION: The hazard rates of young-like
      tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and
      End Results Program, providing a biologic link between normal aging and age
      related tumor aggressiveness. IMPACT: These data show that studies of normal
      tissue gene expression can yield important insights about the pathways and
      biologic pressures that are relevant during tumor etiology and progression.

PMID- 22859399
TI  - 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast
      cancer: evidence from the Breast Cancer Association Consortium.
AB  - BACKGROUND: Our recent genome-wide association study identified a novel breast
      cancer susceptibility locus at 9q31.2 (rs865686). METHODS: To further investigate
      the rs865686-breast cancer association, we conducted a replication study within
      the Breast Cancer Association Consortium, which comprises 37 case-control studies
      (48,394 cases, 50,836 controls). RESULTS: This replication study provides
      additional strong evidence of an inverse association between rs865686 and breast
      cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI),
      0.88; 0.91, P = 2.01 * 10(-29)] among women of European ancestry. There were
      ethnic differences in the estimated minor (G)-allele frequency among controls
      [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other
      Europeans; P for heterogeneity (P(het)) = 1.3 * 10(-143)], but no evidence of
      ethnic differences in per allele OR (P(het) = 0.43). rs865686 was associated with
      estrogen receptor-positive (ER(+)) disease (per G-allele OR, 0.89; 95% CI, 0.86
      0.91; P = 3.13 * 10(-22)) but less strongly, if at all, with ER-negative (ER(-))
      disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 * 10(-6)), with no
      evidence of independent heterogeneity by progesterone receptor or HER2 status.
      The strength of the breast cancer association decreased with increasing age at
      diagnosis, with case-only analysis showing a trend in the number of copies of the
      G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only
      among women with ER(+) tumors. CONCLUSIONS: This study is the first to show that
      rs865686 is a susceptibility marker for ER(+) breast cancer. IMPACT: The findings
      further support the view that genetic susceptibility varies according to tumor
      subtype.

PMID- 22859402
TI  - Interleukin-11 protects against renal ischemia and reperfusion injury.
AB  - Renal ischemia reperfusion (IR) injury causes renal tubular necrosis, apoptosis,
      and inflammation leading to acute and chronic kidney dysfunction. IL-11 is a
      multifunctional hematopoietic cytokine clinically approved to treat chemotherapy
      induced thrombocytopenia. Recent studies suggest that IL-11 also has potent
      antiapoptotic and antinecrotic properties. In this study, we tested the
      hypothesis that exogenous IL-11 protects against renal IR injury and determined
      the mechanisms involved in renal protection. Pretreatment with human recombinant
      IL-11 (HR IL-11) or with long-acting site-specific polyethylene glycol (PEG)
      conjugated human IL-11 analog (PEGylated IL-11) produced partial but significant
      protection against renal IR injury in mice. In addition, HR IL-11 or PEGylated IL
      11 given 30-60 min after IR also provided renal protection in mice. Significant
      reductions in renal tubular necrosis and neutrophil infiltration as well as
      tubular apoptosis were observed in mice treated with HR IL-11 or PEGylated IL-11.
      Furthermore, HR IL-11 or PEGylated IL-11 decreased both necrosis and apoptosis in
      human proximal tubule (HK-2) cells in culture. Mechanistically, IL-11 increased
      nuclear translocation of hypoxia-inducible factor-1alpha (HIF-1alpha) and induced
      sphingosine kinase-1 (SK1) expression and activity in HK-2 cells. Moreover,
      selective HIF-1alpha inhibitors blocked IL-11-mediated induction of SK1 in HK-2
      cells. Finally, HR IL-11 or PEGylated IL-11 failed to protect against renal IR
      injury in SK1-deficient mice. Together, our data show powerful renal protective
      effects of exogenous IL-11 against IR injury by reducing necrosis, inflammation,
      and apoptosis through induction of SK1 via HIF-1alpha.

PMID- 22859403
TI  - Genetic analysis of albuminuria in collaborative cross and multiple mouse
      intercross populations.
AB  - Albuminuria is an important marker of nephropathy that increases the risk of
      progressive renal and chronic cardiovascular diseases. The genetic basis of
      kidney disease is well-established in humans and rodent models, but the causal
      genes remain to be identified. We applied several genetic strategies to map and
      refine genetic loci affecting albuminuria in mice and translated the findings to
      human kidney disease. First, we measured albuminuria in mice from 33 inbred
      strains, used the data for haplotype association mapping (HAM), and detected 10
      genomic regions associated with albuminuria. Second, we performed eight F(2)
      intercrosses between genetically diverse strains to identify six loci underlying
      albuminuria, each of which was concordant to kidney disease loci in humans.
      Third, we used the Oak Ridge National Laboratory incipient Collaborative Cross
      subpopulation to detect an additional novel quantitative trait loci (QTL)
      underlying albuminuria. We also performed a ninth intercross, between genetically
      similar strains, that substantially narrowed an albuminuria QTL on Chromosome 17
      to a region containing four known genes. Finally, we measured renal gene
      expression in inbred mice to detect pathways highly correlated with albuminuria.
      Expression analysis also identified Glcci1, a gene known to affect podocyte
      structure and function in zebrafish, as a strong candidate gene for the
      albuminuria QTL on Chromosome 6. Overall, these findings greatly enhance our
      understanding of the genetic basis of albuminuria in mice and may guide future
      studies into the genetic basis of kidney disease in humans.

PMID- 22859404
TI  - P2X7 deficiency attenuates hypertension and renal injury in deoxycorticosterone
      acetate-salt hypertension.
AB  - The P2X(7) receptor is a ligand-gated ion channel, and genetic variations in the
      P2X(7) gene significantly affect blood pressure. P2X(7) receptor expression is
      associated with renal injury and inflammatory diseases. Uninephrectomized wild
      type (WT) and P2X(7)-deficient (P2X(7) KO) mice were subcutaneously implanted
      with deoxycorticosterone acetate (DOCA) pellets and fed an 8% salt diet for 18
      days. Their blood pressure was assessed by a telemetry system. The mice were
      placed in metabolic cages, and urine was collected for 24 h to assess renal
      function. After 18 days of DOCA-salt treatment, P2X(7) mRNA and protein
      expression increased in WT mice. Blood pressure in P2X(7) KO mice was less than
      that of WT mice (mean systolic blood pressure 133 +/- 3 vs. 150 +/- 2 mmHg). On
      day 18, urinary albumin excretion was lower in P2X(7) KO mice than in WT mice
      (0.11 +/- 0.07 vs. 0.28 +/- 0.07 mg/day). Creatinine clearance was higher in
      P2X(7) KO mice than in WT mice (551.53 +/- 65.23 vs. 390.85 +/- 32.81 MUl.min(
      1).g renal weight(-1)). Moreover, renal interstitial fibrosis and infiltration of
      immune cells (macrophages, T cells, B cells, and leukocytes) were markedly
      attenuated in P2X(7) KO mice compared with WT mice. The levels of IL-1beta,
      released by macrophages, in P2X(7) KO mice had decreased dramatically compared
      with that in WT mice. These results strongly suggest that the P2X(7) receptor
      plays a key role in the development of hypertension and renal disease via
      increased inflammation, indicating its potential as a novel therapeutic target.

PMID- 22859405
TI  - Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic
      humans.
AB  - Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal
      and distal tubule acidification in experimental animals both directly and
      indirectly via increased mineralocorticoid activity. Diet-induced acid loads have
      been shown to increase renal endothelin-1 activity, and it is hypothesized that
      increased dietary acid-induced endothelin-1 activity may be a causative
      progression factor in human renal insufficiency and that this might be reversed
      by provision of dietary alkali. We sought to clarify, in normal human volunteers,
      the role of endothelin-1 in renal acidification and to determine whether the
      effect is dependent on dietary sodium chloride. Acid-base equilibrium was studied
      in seven normal human volunteers with experimentally induced metabolic acidosis
      [NH(4)Cl 2.1 mmol.kg body weight (BW)(-1).day(-1)] with and without inhibition of
      endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist
      bosentan (125 BID p.o./day) both during dietary NaCl restriction (20 mmol/day)
      and NaCl repletion (2 mmol NaCl.kg BW(-1).day(-1)). During NaCl restriction, but
      not in the NaCl replete state, bosentan significantly increased renal net acid
      excretion in association with stimulation of ammoniagenesis resulting in a
      significantly increased plasma bicarbonate concentration (19.0 +/- 0.8 to 20.1 +/
      0.9 mmol/l) despite a decrease in mineralocorticoid activity and an increase in
      endogenous acid production. In pre-existing human metabolic acidosis, endothelin
      1 activity worsens acidosis by decreasing the set-point for renal regulation of
      plasma bicarbonate concentration, but only when dietary NaCl provision is
      restricted.

PMID- 22859406
TI  - Endogenous concentrations of ouabain act as a cofactor to stimulate fluid
      secretion and cyst growth of in vitro ADPKD models via cAMP and EGFR-Src-MEK
      pathways.
AB  - In autosomal-dominant polycystic kidney disease (ADPKD), renal cysts develop by
      aberrant epithelial cell proliferation and transepithelial fluid secretion. We
      previously showed that ouabain increases proliferation of cultured human ADPKD
      cells via stimulation of the EGF receptor (EGFR)-Src-MEK/ERK signaling pathway.
      We examined whether ouabain affects fluid secretion and in vitro cyst growth of
      human ADPKD cell monolayers, ADPKD cell microcysts cultured in a three
      dimensional collagen matrix, and metanephric organ cultures from Pkd1(m1Bei)
      mice. Physiological concentrations of ouabain alone did not affect net
      transepithelial basal-to-apical fluid transport in ADPKD monolayers or growth of
      cultured ADPKD microcysts. In contrast, in the presence of forskolin or 8-bromo
      cAMP, ouabain significantly enhanced ADPKD fluid secretion and microcyst
      expansion. Ouabain exerted this effect by enhancing cAMP-dependent Cl(-)
      secretion via the CFTR. Similarly, ouabain accelerated cAMP-dependent cyst
      enlargement in Pkd1(m1Bei) mice metanephroi, with a more prominent response in
      homozygous than heterozygous mice. Ouabain had no effect on fluid secretion and
      cystogenesis of normal human kidney cells and caused only slight cystic dilations
      in wild-type mouse kidneys. The effects of ouabain in ADPKD cells and Pkd1(m1Bei)
      metanephroi were prevented by inhibitors of EGFR (AG1478), Src (PP2), and MEK
      (U0126). Together, our results show that ouabain, used in physiological
      concentrations, has synergistic effects on cAMP-mediated fluid secretion and cyst
      growth, via activation of the EGFR-Src-MEK pathway. These data provide important
      evidence for the role of ouabain as an endogenous hormone that exacerbates ADPKD
      cyst progression.

PMID- 22859407
TI  - alpha2C-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the
      mouse kidney.
AB  - Targeted deletion or selective pharmacological inhibition of alpha(2C)
      adrenoceptors in mice results in increased brain tissue levels of dopamine and
      its precursor l-3,4-dihydroxyphenylalanine (l-DOPA), without significant changes
      in l-DOPA synthesis. l-DOPA uptake is considered the rate-limiting step in
      dopamine synthesis in the kidney. Since alpha(2C)-adrenoceptors may influence the
      transport of l-DOPA, we investigated the effect of alpha(2C)-adrenoceptor
      activation on l-DOPA uptake in a kidney cell line (opossum kidney cells). l-DOPA
      and dopamine kidney tissue levels in alpha(2C)-adrenoceptor knockout
      (alpha(2C)KO) mice and in mice treated with the selective alpha(2C)-adrenoceptor
      antagonist JP-1302 were also evaluated. The alpha(2)-adrenoceptor agonist
      medetomidine (0.1-1,000 nM) produced a concentration-dependent decrease in l-DOPA
      uptake in opossum kidney cells (IC(50): 2.5 +/- 0.5 nM and maximal effect: 28 +/-
      5% of inhibition). This effect was abolished by a preincubation with JP-1302 (300
      nM). Furthermore, the effect of medetomidine (100 nM) was abolished by a
      preincubation with U-0126 (10 MUM), a MEK1/2 inhibitor. Kidney tissue levels of l
      DOPA were significantly higher in alpha(2C)KO mice compared with wild-type mice
      (wild-type mice: 58 +/- 2 pmol/g tissue and alpha(2C)KO mice: 81 +/- 15 pmol/g
      tissue, P < 0.05) and in mice treated with JP-1302 (3 MUmol/kg body wt) compared
      with control mice (control mice: 62 +/- 2 pmol/g tissue and JP-1302-treated mice:
      75 +/- 1 pmol/g tissue, P < 0.05), both without significant changes in dopamine
      kidney tissue levels. However, mice treated with JP-1302 on a high-salt diet
      presented significantly higher dopamine levels in the kidney and urine compared
      with control animals on a high-salt diet. In conclusion, in a kidney cell line,
      alpha(2C)-adrenoceptor activation inhibits l-DOPA uptake, and in mice, deletion
      or blockade of alpha(2C)-adrenoceptors increases l-DOPA kidney tissue levels.

PMID- 22859408
TI  - Reference ranges for laboratory parameters in ferrets.
AB  - The purpose of this study was to establish reference ranges (robust methods) for
      51 laboratory parameters in ferrets for use in private practice. Current
      literature concerning reference values in ferrets is often based on small patient
      numbers, methods of blood sampling not suitable for practice, and outdated
      laboratory methods. Blood was collected from the V saphena lateralis of 111
      clinically healthy ferrets (age 11 weeks to 9 years; 61 male, 50 female). Age,
      sex (male or female) and fasting status were taken into consideration. Parameters
      evaluated included haematological parameters (packed cell volume, haemoglobin,
      erythrocytes, erythrocyte indices, white blood cells, differential blood counts,
      platelets) (Cell-Dyn3500R; microscopical differential blood count), serum
      parameters (alanine aminotransferase, alkaline phosphatase, aspartate
      aminotransaminase, glutamate dehydrogenase, gamma-glutamyltranspeptidase, lactate
      dehydrogenase, creatine kinase, alpha-amylase, lipase, cholinesterase, glucose,
      fructosamine, total protein, cholesterol, triglycerides, serum bile acids,
      bilirubin, urea, creatinine), serum electrolyte levels (calcium, phosphorus,
      magnesium, sodium, potassium, chloride, iron) (Hitachi 911), and serum hormone
      concentrations (thyroxine, cortisol, oestradiol, progesterone) (Elecsys 1010).
      Results differing from reference ranges reported in current literature were
      attributed in most cases to the use of other blood sampling methods and
      laboratory equipment.

PMID- 22859409
TI  - Biomarkers in dogs surgically treated for ruptured cranial cruciate ligaments.

PMID- 22859410
TI  - Chlamydiosis in British songbirds.

PMID- 22859411
TI  - Serum and urinary adiponectin in dogs with renal disease from leishmaniasis.
AB  - The objective of this study was to perform an analytical validation of a
      commercially available ELISA kit (human adiponectin) for urinary adiponectin
      determination in dogs, and to evaluate urinary adiponectin in dogs with
      glomerular injury. For this purpose, urine samples from three healthy dogs and
      three dogs with diagnosed kidney disease were used for analytical validation of
      the method. In order to evaluate possible influence of kidney damage on urinary
      adiponectin, serum and urine samples from six healthy and 58 dogs with
      leishmaniasis were included. The diseased dogs were allocated to three groups
      according to their urine protein/creatinine (UPC) ratio as non-proteinuric (NP),
      borderline proteinuric (BP), and proteinuric (P). Intra- and inter-assay
      coefficients of variation (CV) were lower than 10 per cent and 12 per cent,
      respectively. Dilutions of canine urine samples resulted in linear regression
      equations close to 1. Mean recovery was of 112 per cent. The detection limit was
      0.75 ng/ml. Urinary adiponectin and urinary adiponectin/creatinine (UAC) ratio
      showed significantly higher values in urine of P group dogs compared with
      healthy, NP and BP dogs. In conclusion, an ELISA kit can be used for precise and
      accurate urinary adiponectin measurement in dogs. Urinary adiponectin is
      increased in dogs with proteinuria suggesting its possible use as a marker of
      kidney damage.

PMID- 22859412
TI  - Progesterone, pregnanediol-3-glucuronide, relaxin and oestrone sulphate
      concentrations in saliva, milk and urine of female alpacas (Vicugna pacos) and
      their application in pregnancy diagnosis.
AB  - The pregnancy-associated hormones, progesterone (P4), pregnanediol-3-glucuronide
      (PdG), relaxin (RLN) and oestrone sulphate (E1S) in plasma, saliva, milk and
      urine of alpacas were measured in order to assess their potential use for
      pregnancy diagnosis. Samples were obtained from 36 female alpacas before mating
      and at different stages throughout pregnancy (confirmed by ultrasonography). The
      hormone concentrations were determined using enzyme immunoassays. Milk samples
      were also tested using a commercial on-farm P4 kit, designed for dairy cattle.
      Although the concentration of P4 in plasma, milk and urine, and the concentration
      of PdG in urine were significantly higher in pregnant than in non-pregnant
      alpacas, there was no difference in the concentrations of P4 or PdG in saliva.
      The on-farm milk P4 kit showed a sensitivity of 90 per cent for diagnosis of
      pregnancy and a specificity of 69 per cent for non-pregnancy. The concentration
      of RLN in plasma increased significantly after the second month, and
      concentration of E1S in plasma and urine during the last month of pregnancy,
      whereas, there were no significant differences in RLN or E1S concentrations in
      saliva and milk between pregnant and non-pregnant alpacas. Values of P4, RLN and
      E1S in plasma, and PdG and E1S in urine are comparable with the previous reports
      in alpacas and, therefore, can be confirmed as an indicator for pregnancy. This
      is the first study to include determination of pregnancy-associated hormones in
      the saliva and milk of alpacas. However, saliva seems to be unsuitable for
      pregnancy diagnosis in alpacas, whereas, P4 in milk, as well as PdG and E1S in
      urine, seem to be adequate tools for diagnosis.

PMID- 22859413
TI  - A comparison between longitudinal shedding patterns of Salmonella Typhimurium and
      Salmonella Dublin on dairy farms.
AB  - Salmonella in cattle herds may behave as epidemic or endemic infections. An
      intensive longitudinal sampling study across all management groups and ages on
      six dairy farms in the UK was used to examine patterns of Salmonella shedding,
      following the prior identification of either Salmonella Dublin (SD) (three farms)
      or Salmonella Typhimurium (ST) (three farms) on the premises in the context of
      clinical salmonellosis. Individual faeces, pooled faeces and environmental
      samples (total 5711 samples), taken approximately every six weeks for 15-24
      weeks, were cultured for Salmonella. SD was detected at low frequency (on any
      visit, 0.5-18.3 per cent of samples positive) and most consistently in calves. By
      contrast, ST was isolated at higher frequency (on any visit, 6.8-75 per cent of
      samples positive), and in higher numbers, up to 10(7) cfu/g faeces. Significantly
      more samples from calves were positive for ST than were positive for SD (50.6 per
      cent v 3.1 per cent; P < 0.001), which was also true for milking cows (46.3 per
      cent v 4.4 per cent; P < 0.001). The differences could help to explain the
      different patterns of bovine infection classically associated with these two
      serovars in the UK. No consistent effect upon shedding was seen among the ST
      infected herds following vaccination.

PMID- 22859414
TI  - Suspected metaldehyde slug bait poisoning in dogs: a retrospective analysis of
      cases reported to the Veterinary Poisons Information Service.
AB  - A retrospective analysis of telephone enquiries to the Veterinary Poisons
      Information Service found 772 cases with follow-up concerning suspected
      metaldehyde slug bait ingestion in dogs between 1985 and 2010. Half the enquiries
      occurred in the summer months. The amount and strength of the slug bait ingested
      was rarely known. In 56, cases the quantity consumed was estimated and was on
      average 229.6 grams of bait. Clinical signs developed in 77.3 per cent of dogs;
      common signs were convulsions, hypersalivation, twitching, hyperaesthesia,
      tremor, vomiting, hyperthermia and ataxia. Only 4.6 per cent of dogs developed
      hepatic changes, and only one developed renal impairment. The average time to
      onset of signs was 2.9 hours post-ingestion, with 50.3 per cent of dogs
      developing effects within one hour. Increased muscle activity (twitching,
      convulsions) lasted on average 15.2 hours. Recovery time was reported in 61 cases
      and occurred on average at 39.3 hours. Common treatments were gut
      decontamination, anticonvulsants, anaesthetics and intravenous fluids. Of the
      dogs that were treated with sedatives, 45.8 per cent required more than one
      sedative or anaesthetic agent. Methocarbamol was rarely used, probably due to
      unavailability. The outcome was reported in 762 dogs; 21.7 per cent remained
      asymptomatic, 61.7 per cent recovered and 16 per cent of dogs died or were
      euthanased. Where known (only six cases), the fatal dose of bait ranged from 4.2
      to 26.7 g/kg (average 11.8 g/kg).

PMID- 22859415
TI  - Guidelines: the new catechism of modern medicine?

PMID- 22859416
TI  - Cognitive impairment and psychopathology in patients with pituitary diseases.
AB  - Patients who are considered to have been successfully treated for pituitary
      disease because they are in long-term remission of functioning or non-functioning
      macroadenomas, still report reduced quality of life and persistent morbidity and
      have (slightly) increased mortality. It is likely that the causes are multi
      factorial, including intrinsic imperfections of surgical or endocrine replacement
      therapy, but also of persistent effects of hormone excess on the central nervous
      system affecting personality and behaviour. In agreement, recent studies
      demonstrate that patients in long-term remission for acromegaly and Cushing's
      disease have a higher prevalence of psychopathology and more maladaptive
      personality traits, display different and less effective coping strategies, and
      experience more negative illness perceptions. These new findings are intriguing
      in view of the general impairments in health-related quality of life, suggesting
      that the effects of previous hormone excess on the central nervous system can be
      long-lasting and to a certain extent even be irreversible. This review aims to
      address the effects of the treatment of pituitary disease on quality of life and
      neuropsychological functioning. Further research is needed to gain more insight
      into irreversibility of hormone excess syndromes. However, since coping
      strategies are altered, it is tempting to speculate that quality of life might be
      improved by targeted interventions.

PMID- 22859417
TI  - Chronic hepatitis E after solid organ transplantation.
AB  - Large outbreaks of acute hepatitis E, caused by hepatitis E virus (HEV) genotypes
      1 and 2, are known from developing countries with suboptimal sanitation
      infrastructure. An increasing incidence of HEV infections is being reported in
      industrialised countries, caused mainly by HEV genotypes 3 and 4, which are often
      found among pigs. Recent evidence suggests that in immunocompromised patients
      about 50% of the cases of acute hepatitis E evolve to chronic hepatitis with
      rapid progression to cirrhosis. Thus, HEV should be considered a cause of chronic
      hepatitis in immunocompromised patients, such as solid organ transplant
      recipients. Because an antibody response to HEV may be absent in these patients,
      an HEV RNA test should be carried out when serum liver tests are elevated over
      months. In small case series, ribavirin has been shown to represent a promising
      treatment option for chronic HEV infection. To increase the awareness for HEV
      infection in immunocompromised patients, a representative case report of an HEV
      infected renal transplant recipient with chronic hepatitis E, successfully
      treated with ribavirin, is presented. Studies are required to determine the
      optimal duration of ribavirin therapy and to assess outcome for solid organ
      transplant recipients with chronic HEV infection.

PMID- 22859418
TI  - Kidney injury during VEGF inhibitor therapy.
AB  - Antiangiogenic therapy targeting vascular endothelial growth factor (VEGF) or its
      receptor (VEGFR) has proven its effect in the treatment of several types of
      cancer, including renal cell carcinoma (RCC). However, treatment can be
      accompanied by notable adverse effects. Mild proteinuria and hypertension are
      often seen, but sometimes nephrotic range proteinuria and/or renal insufficiency
      develop. In recent years insight into the toxic effects of anti-VEGF therapy in
      the kidney has increased. A few biopsies have been done and thrombotic
      microangiopathy is reported in the majority of cases. However, other patterns of
      kidney injury have been described as illustrated by the case of a 62-year-old
      patient who presented two years after initiation of the VEGFR inhibitor cediranib
      with a nephrotic syndrome and acute renal failure. Kidney biopsy disclosed focal
      segmental glomerulosclerosis (FS GS) and interstitial nephritis. Partial
      remission was achieved after stopping the cediranib and a short course of
      prednisone. We review the different forms of kidney injury that could be caused
      by anti-VEGF therapy.

PMID- 22859419
TI  - The economics of mesalazine in active ulcerative colitis and maintenance in the
      Netherlands.
AB  - BACKGROUND: In this study we investigate the costs and benefits of topical
      mesalazine combined with oral mesalazine therapy for active ulcerative colitis
      (UC), and once daily (OD ) mesalazine 2 grams versus twice daily (BID ) for
      maintaining UC remission. METHODS: Two decision analytic models were constructed
      to evaluate treatment costs and quality-adjusted life years (QALYs) associated
      with mesalazine. The first model explored 4 g oral mesalazine in combination with
      1 g topical mesalazine during active UC compared with 4 g oral mesalazine
      monotherapy for achieving clinical remission. The second model compared remission
      rates at one year for OD 2 g oral mesalazine compared with BID 1 g adjusted for
      compliance. All direct costs were obtained from established treatment costs in
      the Netherlands. RESULTS: The average cost of treatment to transition an active
      UC patient into remission using oral plus topical mesalazine or oral mesalazine
      monotherapy was v2207 (95% CI: v1402 to v3332) and v2945 (95% CI: v1717 to
      v4592), respectively. The annual average cost-saving of adding topical mesalazine
      delivered for four weeks during active UC was v738. The average annual costs of
      maintenance of remission with OD and BID therapy were v1293 (95% CI: v1062 to
      v1496) and v1502 (95% CI: v1262 to 1708), respectively with an annual average per
      person savings of v209. CONCLUSION: Topical mesalazine during acute UC flares
      results in lower costs due to reduced healthcare consumption attributed to faster
      symptom resolution. Furthermore, as a result of lower costs and modest QALY
      gains, maintenance therapy using OD mesalazine is the dominant treatment option
      if compared with BID mesalazine.

PMID- 22859420
TI  - APOE1 mutation in a patient with type III hyperlipoproteinaemia: detailed genetic
      analysis required.
AB  - We present the case of a patient with clinical features of familial
      dysbetalipoproteinaemia (FD) including high levels of total cholesterol,
      hypertriglyceridaemia and the presence of palmar xanthomas. Whereas genotype
      analysis identified the APOE3E3 isoform, sequence analysis revealed the presence
      of one APOE1 allele due to a mutation, p.Lys164Glu, which leads to loss of
      function of apolipoprotein E (ApoE), a rare cause of dominant FD.

PMID- 22859421
TI  - Altered mental status in a young male.

PMID- 22859422
TI  - Green coloured urine.

PMID- 22859423
TI  - Intra-thoracic mass on CT in a breast cancer patient.

PMID- 22859425
TI  - Vitamin D, or wait and see?

PMID- 22859424
TI  - What do professionals recommend regarding the frequency of self-monitoring of
      blood glucose?
AB  - BACKGROUND: Patients' adherence to guidelines regarding self-monitoring of blood
      glucose (SMBG) is limited. However, there are no previous reports about the
      recommendations that are given in clinical practice concerning SMBG. The aim of
      this study was to investigate what healthcare providers recommend to insulin
      treated patients with diabetes regarding frequency and timing of SMBG. METHODS:
      In this cross-sectional descriptive study, primary care assistants, diabetes
      specialised nurses and doctors in the Netherlands were invited via e-mail to
      complete an internet survey. RESULTS: A total of 980 (14%) professionals returned
      the questionnaire. Insulin pump users and patients with type 1 diabetes (T1DM) on
      4 injections a day were advised to perform SMBG daily by 96% and 63% of the
      professionals, respectively. The majority of the professionals advised these
      patients to perform 3-4 measurements per day. There was less agreement on the
      timing (pre- and/or postprandial). Patients with type 2 diabetes (T2DM) on four
      injections were advised to perform SMBG less frequently. There was a wide
      variation in recommendations that were given to patients with T2DM on less
      intensive insulin regimens. CONCLUSION: This study investigated SMBG from a
      professional's perspective. A considerable and relevant variation in the
      recommendations about the number and timing of SMBG was observed. The most
      striking differences were found in patients with T2DM on less intensive insulin
      regimes, also with respect to the frequency of SMBG. Well-designed studies are
      necessary in order to give a more evidence-based advice on the basic frequency
      and timing of SMBG.

PMID- 22859426
TI  - Vinorelbine chemotherapy-induced blistering.

PMID- 22859427
TI  - Permanent neonatal diabetes: different aetiology in Arabs compared to Europeans.
AB  - OBJECTIVE: Mutations in the KCNJ11 and ABCC8 genes that encode the pancreatic
      K(ATP) channel are the commonest cause of permanent neonatal diabetes mellitus
      (PNDM). The authors aimed to define the genetic causes of PNDM in a large cohort
      of Arab patients and compare them with a British cohort tested in the same
      laboratory. DESIGN: Retrospective observational study. SETTING: International
      genetics centre. PATIENTS: Arab and British subjects with PNDM who were referred
      for genetic testing over the same period. INTERVENTION: Comparison of genotypes
      and phenotypes between the two cohorts. MAIN OUTCOME MEASURES: The aetiology and
      phenotype of PNDM in an Arab compared to a British cohort. RESULTS: 88 Arab and
      77 British probands were referred between 2006 and 2011, inclusive. Consanguinity
      was higher among Arabs (63.6% vs 10.4%) and a higher percentage had a genetic
      diagnosis compared to the British cohort (63.6% vs 41.6%). Recessive EIF2AK3 gene
      mutations were the commonest cause of PNDM in the Arab cohort (22.7%) followed by
      INS (12.5%), and KCNJ11 and GCK (5.7% each), whereas K(ATP) channel mutations
      were the commonest cause (29.9%) in the British cohort. In 37.5% of Arab patients
      PNDM was part of a genetic syndrome compared to 7.8% of the British cohort.
      CONCLUSION: PNDM in the Arab population has a different genetic spectrum compared
      to British patients where KATP channel mutations are the commonest cause, similar
      to other European populations. In Arabs, PNDM is more likely to be part of a
      recessively inherited syndrome, possibly due to the higher rate of consanguinity.

PMID- 22859428
TI  - Question 1. Chloral hydrate or midazolam: which is better for sedating children
      for painless diagnostic imaging?

PMID- 22859429
TI  - Towards evidence based medicine for paediatricians.

PMID- 22859430
TI  - Question 2. How effective is domperidone at reducing symptoms of gastro
      oesophageal reflux in infants?

PMID- 22859431
TI  - Question 3. Should stimulants be administered to manage difficulties with
      attention, hyperactivity and impulsivity following paediatric acquired brain
      injury?

PMID- 22859432
TI  - Can we have a permanent end to 'temporary brittle bone disease'?

PMID- 22859433
TI  - Editorial response to 'can we have a permanent end to "temporary brittle bone
      disease"?'.

PMID- 22859434
TI  - Type of high-school credentials and older age ADL and IADL limitations: is the
      GED credential equivalent to a diploma?
AB  - PURPOSE: Educational attainment is a robust predictor of disability in elderly
      Americans: older adults with high-school (HS) diplomas have substantially lower
      disability than individuals who did not complete HS. General Educational
      Development (GED) diplomas now comprise almost 20% of new HS credentials issued
      annually in the United States but it is unknown whether the apparent health
      advantages of HS diplomas extend to GED credentials. This study examines whether
      adults older than 50 years with GEDs have higher odds of incident instrumental or
      basic activities of daily living (IADLs) limitations compared with HS degree
      holders. METHODS: We compared odds of incident IADL limitations by HS credential
      type using discrete-time survival models among 9,426 Health and Retirement Study
      participants followed from 1998 through 2008. RESULTS: HS degree holders had
      lower odds of incident IADLs than GED holders (OR = 0.72, 95% CI = 0.58, 0.90 and
      OR = 0.69, 95% CI = 0.56, 0.86 for ADLs and IADLs, respectively). There was no
      significant difference in odds of incident IADL limitations between GED holders
      and respondents without HS credentials (OR = 0.89, 95% CI = 0.71, 1.11 for ADLs;
      OR = 0.88, 95% CI = 0.70, 1.12 for IADLs). IMPLICATIONS: Although GEDs are widely
      accepted as equivalent to high school diplomas, they are not associated with
      comparable health advantages for physical limitations in older age.

PMID- 22859435
TI  - Health-related quality of life: expanding a conceptual framework to include older
      adults who receive long-term services and supports.
AB  - For older adults receiving long-term services and supports (LTSS), health-related
      quality of life (HRQoL) has emerged as a critical construct to examine because of
      its focus on components of well-being, which are affected by progressive changes
      in health status, health care, and social support. HRQoL is a health-focused
      quality of life (QOL) concept that encompasses aspects of QOL that affect health
      such as function, physical, and emotional health. Examining existing theoretical
      constructs and indicators of HRQoL among LTSS recipients led us to posit a
      revised conceptual framework for studying HRQoL among LTSS recipients. We adapted
      the Wilson and Cleary HRQoL model by expanding function to specifically include
      cognition, adding behavior and LTSS environmental characteristics in order to
      create a more robust HRQoL conceptual framework for older adults receiving LTSS.
      This refined conceptual model allows for the measurement of a mix of structural,
      process, and outcome measures. Continued development of a multidimensional
      conceptual framework with specific HRQoL measures that account for the unique
      characteristics of older adults receiving LTSS will contribute significantly to
      LTSS research, policy, and planning efforts.

PMID- 22859436
TI  - The influence of unpaid work on the transition out of full-time paid work.
AB  - PURPOSE: Continued employment after retirement and engagement in unpaid work are
      both important ways of diminishing the negative economic effects of the
      retirement of baby boomer cohorts on society. Little research, however, examines
      the relationship between paid and unpaid work at the transition from full-time
      work. Using a resource perspective framework this study examines how engagement
      in unpaid work prior to and at the transition from full-time work influences
      whether individuals partially or fully retire. DESIGN AND METHODS: This study
      used a sample of 2,236 Americans between the ages 50 and 68, who were interviewed
      between 1998 and 2008. Logistic regression was used to estimate transitioning
      into partial retirement (relative to full retirement) after leaving full-time
      work. RESULTS: We found that the odds of transitioning into part-time work were
      increased by continuous volunteering (78%) and reduced by starting parental
      (84%), grandchild (41%), and spousal (90%) caregiving and unaffected by all other
      patterns of engagement in unpaid work. IMPLICATIONS: Our findings suggest that
      volunteering is complementary with a transition to part-time work, and starting a
      new caregiving role at this transitioncreates a barrier to continued employment.
      In order to provide workers the opportunity to engage in the work force longer at
      the brink of retirement, it may be necessary to increase the support mechanisms
      for those who experience new caregiving responsibilities.

PMID- 22859438
TI  - Hospital readmission among older adults who return home with unmet need for ADL
      disability.
AB  - PURPOSE: This study determined whether returning to the community from a recent
      hospitalization with unmet activities of daily living (ADL) need was associated
      with probability of readmission. METHODS: A total of 584 respondents to the 1994,
      1999, and/or 2004 National Long-Term Care Surveys (NLTCS) who were hospitalized
      within 90 days prior to the interview and reported ADL disability at the time of
      the interview were considered for analysis. Medicare claims linked to the NLTCS
      provided information about hospital episodes, so those enrolled in Health
      Maintenance Organizations or Veterans Affairs Medical Centers were not included
      (n = 62), resulting in a total sample size of 522. ADL disability was defined as
      needing human help or equipment to complete the task. Unmet ADL need was defined
      as receiving inadequate or no help for one or more ADL disabilities. Disability
      that began within 90 days of the interview was considered new disability.
      RESULTS: After adjusting for demographic, health, and functioning
      characteristics, unmet ADL need was associated with increased risk for hospital
      readmission (HR: 1.37, 95% CI: 1.03-1.82). Risk of readmission was greater for
      those with unmet need for new disabilities than those with unmet need for
      disabilities that were present before the index hospitalization (HR: 1.66, 95%
      CI: 1.01-2.73). IMPLICATIONS: Many older patients are discharged from the
      hospital with ADL disability. Those who report unmet need for new ADL
      disabilities after they return home from the hospital are particularly vulnerable
      to readmission. Patients' functional needs after discharge should be carefully
      evaluated and addressed.

PMID- 22859439
TI  - Predicting breast cancer chemotherapeutic response using a novel tool for
      microarray data analysis.
AB  - We developed a novel tool for microarray data analysis that can parsimoniously
      discover highly predictive genes by finding the optimal trade off between fold
      change and t-test p value through rigorous cross validation. In addition to find
      a small set of highly predictive genes, the tool also has a procedure that
      recursively discovers and removes predictive genes from the dataset until no such
      genes can be found. We applied our tool to a public breast cancer dataset with
      the goal to discover genes that can predict patient&rsquo;s response to a
      preoperative chemotherapy. The results show that estrogen receptor (ER) gene is
      the most important gene to predict chemotherapeutic response and no gene
      signatures can add much clinical benefit for the whole patient population. We
      further identified a clinically homogenous subgroup of patients (ER-negative, PR
      negative and HER2-negative) whose response to the chemotherapy can be reasonably
      predicted. Many of the discovered predictive markers for this subgroup of
      patients were successfully validated using a blinded validation set.

PMID- 22859437
TI  - Regional variation of racial disparities in mental health service use among older
      adults.
AB  - PURPOSE: Given the paucity of research on the role of geography in mental health
      care, this study examined whether racial differences in mental health service use
      varied across geographic regions among older adults. DESIGN AND METHODS: Drawn
      from the Collaborative Psychiatric Epidemiology Surveys (CPES), blacks (n =
      1,008) and whites (n = 1,870) aged 60 and older were selected for analysis.
      Logistic regression analyses were conducted. RESULTS: Results showed significant
      racial disparities in mental health service use in the overall sample, as well as
      significant variation by region. Although no racial differences were observed in
      the Northeast, West, or Midwest regions, black elders in the South were
      significantly less likely than whites to use mental health services (odds ratios
      [OR], 2.08; 95% confidence interval [CI], 1.34-3.23). IMPLICATIONS: The findings
      suggest that improving the access to mental health care in certain regions, the
      South in particular, may be essential to reduce racial disparities at the
      national level. Policy implications are discussed.

PMID- 22859440
TI  - Extraction and structural analysis of glycosaminoglycans from formalin-fixed,
      paraffin-embedded tissues.
AB  - Glycosaminoglycans (GAGs) are long, anionic polysaccharides involved in many
      basic aspects of mammalian physiology and pathology. Here we describe a method to
      extract GAGs from formalin-fixed, paraffin-embedded tissues and found that they
      are structurally comparable with GAGs extracted from frozen tissues. We employed
      this method to structurally characterize GAGs in tissues, including laser
      dissected layers of skin and pathological specimens. This method enables the use
      of the archival paraffin-embedded material for detailed (structural) analysis of
      GAGs.

PMID- 22859441
TI  - Primary dysmenorreah-leading problem of adolescent gynecology (review).
AB  - Adolescent gynecology is a rapidly developing area. Dysmenorrhea is one of the
      most common complaints among women of young reproductive age. About 25-95% of
      young women suffers with dysmenorrhoea and is associated with significant
      psychological, physical, behavioral and social distress. This review summarizes
      epidemiology, strategies of establishing the diagnosis, discussion of
      pathophysiology of the disease and risk factors. We performed a comprehensive
      search through MEDLINE, EMBASE, Scopus, MD consult and Web of Science. Inclusion
      criteria specified review and research articles reporting primary dysmenorreah in
      adolescents. The search resulted in 214 articles. We point out a variety of
      noninvasive nutritional and psychological therapeutic interventions that have
      been suggested to relieve dysmenorrheal. This review of Primary Dysmenorreah
      identifies gaps in the literature, some contradictions and highlights the need
      for further study.

PMID- 22859442
TI  - Distribution of erythrocyte phenotypic groups in women with benign tumors of the
      uterus in Adjara Oncology Centre.
AB  - ABO blood groups antigens have biological and clinical significance. The ABO
      blood groups antigens has been associated with many diseases, though the
      explanation between ABO blood groups and disease is still unclear. The aim of
      this study is to investigate the presence of a possible association between
      benign tumors of the utesus with blood ABO, RhD, Kell and MN groups in women in
      reproductive periods. In diseased population (60 subject) was investigated for
      Erythrocyte phenotypic groups antigens. Immunoserological methods have been used
      to identify the antigens. The obtained results were statistically processed. High
      frequencies of A (43,3+/-3,2%), D(91,6+/-3,5%) and Kell (+) (26.66+/-5.7 %)
      antigens were found in diseased of benign tumors of uterus comparison with donor.
      The researches shows, that is increased risk of disease development in carriers
      of these phenotypes. In summary, according our research we've thought, that blood
      groups may be a marker for bening tomors of the uterus. Based on these data,
      these could be used as prognostic factor for bening tomors of the uterus. The
      study of Erythrocyte group antigens in diseased we may to identify "high risk"
      individuals, that help to find ways, which help to control of disease.

PMID- 22859443
TI  - Non-convulsive status epilepticus in comatose patients (case reports).
AB  - Non-convulsive status epilepticus (NCSE) is relatively rare, but recognized
      condition observed in non-epileptic comatose patients. In coma state NCSE may be
      precipitated by stroke, severe electrolyte disturbance, acute intoxication,
      infection, traumatic brain injury and etc. All these critical disorders can cause
      coma themselves and without clinical EEG investigation it is impossible to
      attribute impaired consciousness to NCSE, while the condition can be responsive
      to anticonvulsant medication. The proper and rapid diagnosis of NCSE is
      challenging, because it can severely impact the patient and often is a treatable
      and completely reversible state. Case reports describe the state of three
      comatose patients affected by severe neurological disorders, who were diagnosed
      as NCSE after EEG investigation. Nor of these patients were noted to have the
      epileptic seizures and convulsions. The patients were treated with different
      anticonvulsive medications (Finlepsin, Levetiracetam, Depakin) and fully
      recovered from coma state. Frequently, physicians could not suspect presence of
      NCSE in patients with impaired consciousness because of sufficiently complicated
      underlying illness. Apparently, clinical EEG investigation is useful to be
      performed in all comatose patients.

PMID- 22859444
TI  - [Alpha-dephenzine concentration in peripheral blood of patients diagnosed with
      schizophrenia].
AB  - Over the past few decades the search for predisposed biological markers has
      become the course of most priority in scientific psychiatry. Research goal was to
      reveal the association of alpha-dephenzine concentration in peripheral blood with
      the disease existence and its progressing (acute and chronic forms) in patients
      with schizophrenia. In-patients diagnosed with schizophrenia have been
      investigated (av. age - 45.33+/-1.86), among them 26 males (av. age - 39.41+/
      1.86) and 13 females (av. age - 45.04+/-2.44). 27 patients with acute form of
      schizophrenia (av.age - 44.88+/-2.42), 12 patients with a chronic form (av. age -
      46.33+/-2.75). 15 healthy volunteers have been investigated as well (av.age -
      40.03+/-2.94), 5 males and 10 females among them. The study of alpha-dephenzine
      concentration by the immunoenzyme method has been implied in the investigation.
      Research studies revealed statistically valid increased concentration of alpha
      dephenzine in patients diagnosed with schizophrenia comparing with healthy
      volunteers. The difference was so evident that qualitative difference (marker
      existence-nonexistence) would rather be considered than quantitative one. Relying
      on the results of studies we can estimate alpha-dephenzines as possible
      biomarkers of schizophrenia.

PMID- 22859445
TI  - Distribution and impact of erythrocyte Lewis-system antigens on patients with
      ischemic heart diseases in the west of Georgia.
AB  - The aim of the research is to reveal the cases of Lewis System Antigens Phenotype
      in West Georgia and setting the connection between antigens expressivness and
      IHD. Therefore, we have phenotypically tested 393 people (236 healthy donors;
      average age 42+/-7,5 and 157 patients ill with ischemic heart diseases; average
      age 62,5+/-7,5). In accordance with the findings, the number of Lewis -antigens
      among healthy population is 46,6% (110 +/-4,8; p<0.05) with Lea-b+ phenotype;
      30,9% - with Lea-b- phenotype(73+/-2,9; p<0.03); 19% - with Lea+b- phenotype
      (47+/-1,7; p<0.03) Only 2,6% cases of phenotype Lea+b+ (6+/-0,2; p<0.02),were
      revealed among healthy population. As for the patients with ischemic heart
      diseases we got the following results: 41% cases of Lea-b- phenotype (65+/-3,9;
      p<0.05); 32,8% - Lea-b+ (51+/-3,2; p<0.03); 21,1% - Lea+b- - phenotype 33+/-2,9;
      p<0.03) and 5,6% - Lea+b+ phenotype (8+/-1,2; p<0.02). On the whole, in the West
      Georgia the most frequent phenotype is Lea-b+ among healthy population and Lea-b-
      phenotype among people with ischemic heart diseases. Research was carried out in
      a control group according to Lewis antigen phenotype. People were separated in
      two groups; I group -healthy people with Lea-b- phenotype and II group - healthy
      people with Lea-b+ and Lea+b- phenotypes. On the basis of the research we
      concluded that people in the first group (with Lea-b- phenotype) had a high BMI,
      arterial hypertension and lower indexes of high density lipoprotein and
      triglyceride than the people in the second group(with Lea-b+ and Lea+b-
      phenotypes. These kinds of changes (characterised to the people with Lea-b-
      phenotype) are associated with a high risk of ischemic diseases and
      atherosclerosis. To sum up, people with Lea-b- phenotype have a high risk of
      ischemic heart disease. In accordance with the findings, Lewis phenotype research
      can be carried out to detect HID and other diseases as well (hypertension,
      ischemic insult and insulin-dependent diabetes mellitus).

PMID- 22859446
TI  - The role of interleukin-10 in patients with HCV infection.
AB  - The aim of investigation was to study cytokine-producing ability of blood immune
      cells in type of viral hepatitis C, correlation with the degree of hepatic lesion
      and liver cirrhosis. 130 patients were investigated: 72 with cirrhosis: among
      them 10 - with stage A, 14 - with stage B and 48 - with stage C. The study
      demonstrates significant changes of cytokine-producing ability of blood immune
      cells type of viral hepatitis C, correlation with the degree of hepatic lesion
      and liver cirrhosis. The results showed that various types of chronic viral
      hepatitis C and stages of cirrhosis were associated with misbalance in production
      of anti-inflammatory cytokine, i.e. a significant rise of interleukin-10
      concentration, which were the most prominent in cases of severe hepatic lesion.

PMID- 22859447
TI  - [The study of the structure of the diseases among hospitalized pediatric patients
      from different geographical regions of Armenia].
AB  - The aim of the research was to reveal the structure of disease among hospitalized
      (2003-2009) pediatric patients. The author found that in different years it
      underwent certain changes but respiratory diseases, innate defects and perinatal
      problems constantly prevailed. The study showed that in all geographical areas
      respiratory diseases, congenital abnormalities (development abnormalities),
      defects and chromosomal abnormalities and certain states arising in the perinatal
      period always prevail. The study showed that the situation in all geographical
      areas of Armenia is the same, which means that the challenges facing the
      pediatric service in all geographical areas are almost the same in content and
      form.

PMID- 22859448
TI  - [The structure of somatic pathology according to sex in hospitalized pediatric
      patients in Armenia].
AB  - The aim of the investigation was the analyzes of somatic pathology according to
      sex in hospitalized pediatric patients in Armenia in 2003-2009. The study showed
      the prevail of respiratory diseases, congenital abnormalities, defects and
      chromosomal abnormalities and certain states arising in the perinatal period. The
      structure of diseases according to sex showed boys and girls itself is somewhat
      different, which may suggest diversity of the undertaken activities, especially
      in developing tactics and strategies for prevention and treatment of such
      patients.

PMID- 22859449
TI  - Cholinergic stimulation of adrenal medulla is essential for the
      granulicytopoietic response to lithium.
AB  - Granulocytopoietic response to lithium carbonate (Li+) in rat was eliminated
      completely by N-cholinergic blocking agent, and independently by alpha-1
      adrenergic antagonist. A link between these two contradictory events is explained
      by release of acetylcholine from the cholinergic preganglionic nerve endings in
      adrenal medulla triggered by Li+, and subsequent discharge of catecholamines (CA)
      from medullar chromaffin cells, which on their part activate adrenergic receptors
      of alpha-1 class on hematopoietic progenitor cells. Respectively,
      granulocytopoietic response to Li+ is blocked by cholinergic N-blocking agent at
      the level of adrenal medulla, and by the alpha-adrenergic blocking agent at the
      level of the hematopoietic cells proper. The stimulatory action of Li+ on
      granulocytopoietic cells is indirect, while is mediated by CA release from
      adrenal chromaffine cells. At the initial stages of leukocyte restitution in the
      acute myelotoxic leucopenia relative increase in "large" lymphocyte fraction
      (Lge) preceding the increment in granulocyte counts is evident. In this fraction
      of lymphocytes peripheral blood progenitor cells (PBPC) are expected.

PMID- 22859450
TI  - [Fatty acids of grape seed oil and its biological activity as 1,0% and 2,5% food
      additive].
AB  - Using high-performance liquid chromatography were qualitatively and
      quantitatively identified high fatty acids contained in grape seed oil and
      compare its biological activity as 1,0% and 2,5% food-additive an fatty acids
      composition contained in lipids of mice livers. Investigation were carried out on
      90 inbred mice 5,0 g weight. Using high-performance liquid chromatography methods
      in grape seed oil is identified linoleic (65,0%), linolenic (1,5%), oleic
      (17,0%), palmitic (8,0%), stearic (4,4%) and arachidonic (0,6%) acids. After 15
      days fatty acids are carried out from mouse liver and individual identified. In
      paper is showed that 1,0% and 2,5% grape seed oil food-additive have a different
      biological activity. The investigation demonstrated that after 15 days the grape
      seed oil takes marked part in lipid metabolism of biological necessary
      components.

PMID- 22859451
TI  - [Application of bacterial thermo- and phagelysates for suppression of malignant
      tumor growth in experimental studies: 2 comparative analysis of anticancer
      efficacy of thermo- and phagelysates of Ps. aeruginosa and E. coli].
AB  - In the presented work antitumor effects of thermo- and phagelysates of
      Ps.aeruginosa and E.coli on Ehrlich carcinoma growth in mice have been studied.
      The treatment efficacy was evaluated according to the dynamic changes in volume
      of cancer tissue, cancer growth inhibition percent and calculations using Semi
      empirical mathematical model describing cancer volume variations in relation to
      time passed after carcinoma inoculation. It was shown that at the early stage of
      cancer growth all tested bacterial preparations significantly inhibit cancer
      growth. Antitumor treatment effects were better expressed in animal studies using
      bacterial pagelysates in comparison to that of thermolysates. Comparative
      analysis of anticancer treatment efficacy of Ps.aeruginosa and E.coli
      phagelysates have shown that E.coli phagelysates reveal stronger and more
      prolonged anticancer treatment properties than phagelysates of Ps.aeruginosa.

PMID- 22859452
TI  - [Rheologic properties of some pharmaceutical excipients in drug forms and
      cosmetic preparation technology].
AB  - The establishment of mechanisms and principles of the formation of deformation
      (fracture) of spatial structure of bentonite solutions and various solutions and
      disperse systems is one or the most important problems of modern pharmaceutical
      technology. The article presents the results of a long-term research of influence
      of high-molecular compounds and surfactants on the properties of designed dosage
      drug forms and cosmetic preparation. Research data, as the basis for drug
      combinations "gel" with dekamitoksin, extract Aesculus hippocastanum L and
      probiotics.

PMID- 22859453
TI  - [Morphological changes of the intestine in experimental acute intestinal
      infection in the treatment of colloidal silver].
AB  - At the present stage of infectionist practice in the treatment of acute
      intestinal infections caused by opportunistic microorganisms, colloidal silver is
      used with a particle size of 25 nm as an alternative to conventional causal
      therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy,
      got colloidal silver; with a modeled acute intestinal infection in the basic
      treatment and with the addition of colloidal silver), histological examination
      was performed of small and large intestine of rats. Oral administration of
      colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes
      in morphometric parameters compared to the norm, and during early convalescence
      in rats with acute intestinal infections were observed destructive and
      compensatory changes in the intestine, which depended on the treatment regimen.
      With the introduction of colloidal silver decreased activity of the inflammatory
      process and the severity of morphological changes in tissues of small and large
      intestine, indicating that the positive effect of study drug compared with
      baseline therapy.

PMID- 22859455
TI  - NIH basics.

PMID- 22859460
TI  - HIV/AIDS. Dreams meet realities at AIDS conference.

PMID- 22859461
TI  - Developmental biology. Multicellularity driven by bacteria.

PMID- 22859462
TI  - Newsmaker interview: John Grunsfeld. NASA's spacefaring science chief sets a new
      course for Mars. Interview by Yudhijit Bhattacharjee.

PMID- 22859463
TI  - Archaeology. Ice Age tools hint at 40,000 years of Bushman culture.

PMID- 22859464
TI  - Metabolomics. London's Olympic drug testing lab to become national phenome
      center.

PMID- 22859465
TI  - Polio campaign. The polio emergency.

PMID- 22859466
TI  - Polio campaign. Fighting polio in Pakistan.

PMID- 22859467
TI  - Polio campaign. Closing a deadly refuge.

PMID- 22859468
TI  - Chinese addiction study and human rights.

PMID- 22859470
TI  - Battling bias at NIH.

PMID- 22859472
TI  - Research ethics. Aligning regulations and ethics in human research.

PMID- 22859473
TI  - Molecular biology. Outsourcing genome protection.

PMID- 22859474
TI  - Materials science. Approaching asymmetry and versatility in polymer assembly.

PMID- 22859475
TI  - Systems biology. Modular biological complexity.

PMID- 22859476
TI  - Ecology. How did the cuckoo get its polymorphic plumage?

PMID- 22859477
TI  - Retrospective. F. Herbert Bormann (1922-2012).

PMID- 22859478
TI  - Black holes. Inescapable pull. Introduction.

PMID- 22859479
TI  - Classical black holes: the nonlinear dynamics of curved spacetime.
AB  - Numerical simulations have revealed two types of physical structures, made from
      curved spacetime, that are attached to black holes: tendexes, which stretch or
      squeeze anything they encounter, and vortexes, which twist adjacent inertial
      frames relative to each other. When black holes collide, their tendexes and
      vortexes interact and oscillate (a form of nonlinear dynamics of curved
      spacetime). These oscillations generate gravitational waves, which can give kicks
      up to 4000 kilometers per second to the merged black hole. The gravitational
      waves encode details of the spacetime dynamics and will soon be observed and
      studied by the Laser Interferometer Gravitational Wave Observatory and its
      international partners.

PMID- 22859480
TI  - Quantum mechanics of black holes.
AB  - The popular conception of black holes reflects the behavior of the massive black
      holes found by astronomers and described by classical general relativity. These
      objects swallow up whatever comes near and emit nothing. Physicists who have
      tried to understand the behavior of black holes from a quantum mechanical point
      of view, however, have arrived at quite a different picture. The difference is
      analogous to the difference between thermodynamics and statistical mechanics. The
      thermodynamic description is a good approximation for a macroscopic system, but
      statistical mechanics describes what one will see if one looks more closely.

PMID- 22859481
TI  - Stellar-mass black holes and ultraluminous x-ray sources.
AB  - We review the likely population, observational properties, and broad implications
      of stellar-mass black holes and ultraluminous x-ray sources. We focus on the
      clear empirical rules connecting accretion and outflow that have been established
      for stellar-mass black holes in binary systems in the past decade and a half.
      These patterns of behavior are probably the keys that will allow us to understand
      black hole feedback on the largest scales over cosmological time scales.

PMID- 22859482
TI  - The formation and evolution of massive black holes.
AB  - The past 10 years have witnessed a change of perspective in the way
      astrophysicists think about massive black holes (MBHs), which are now considered
      to have a major role in the evolution of galaxies. This appreciation was driven
      by the realization that black holes of millions of solar masses and above reside
      in the center of most galaxies, including the Milky Way. MBHs also powered active
      galactic nuclei known to exist just a few hundred million years after the Big
      Bang. Here, I summarize the current ideas on the evolution of MBHs through cosmic
      history, from their formation about 13 billion years ago to their growth within
      their host galaxies.

PMID- 22859483
TI  - Transformation optics and subwavelength control of light.
AB  - Our intuitive understanding of light has its foundation in the ray approximation
      and is intimately connected with our vision. As far as our eyes are concerned,
      light behaves like a stream of particles. We look inside the wavelength and study
      the properties of plasmonic structures with dimensions of just a few nanometers,
      where at a tenth or even a hundredth of the wavelength of visible light the ray
      picture fails. We review the concept of transformation optics that manipulates
      electric and magnetic field lines, rather than rays; can provide an equally
      intuitive understanding of subwavelength phenomena; and at the same time can be
      an exact description at the level of Maxwell's equations.

PMID- 22859484
TI  - Non-centrosymmetric cylindrical micelles by unidirectional growth.
AB  - Although solution self-assembly of block copolymers (BCPs) represents one of the
      most promising approaches to the creation of nanoparticles from soft matter, the
      formation of non-centrosymmetric nanostructures with shape anisotropy remains a
      major challenge. Through a combination of crystallization-driven self-assembly of
      crystalline-coil BCPs in solution and selective micelle corona cross-linking, we
      have created short (about 130 nanometers), monodisperse cylindrical seed micelles
      that grow unidirectionally. These nanostructures grow to form long, non
      centrosymmetric cylindrical A-B and A-B-C block co-micelles upon the addition of
      further BCPs. We also illustrate the formation of amphiphilic cylindrical A-B-C
      block co-micelles, which spontaneously self-assemble into hierarchical star
      shaped supermicelle architectures with a diameter of about 3 micrometers. The
      method described enables the rational creation of non-centrosymmetric, high
      aspect ratio, colloidally stable core-shell nanoparticles in a manner that until
      now has been restricted to the biological domain.

PMID- 22859485
TI  - Aerosols from overseas rival domestic emissions over North America.
AB  - Many types of aerosols have lifetimes long enough for their transcontinental
      transport, making them potentially important contributors to air quality and
      climate change in remote locations. We estimate that the mass of aerosols
      arriving at North American shores from overseas is comparable with the total mass
      of particulates emitted domestically. Curbing domestic emissions of particulates
      and precursor gases, therefore, is not sufficient to mitigate aerosol impacts in
      North America. The imported contribution is dominated by dust leaving Asia, not
      by combustion-generated particles. Thus, even a reduction of industrial emissions
      of the emerging economies of Asia could be overwhelmed by an increase of dust
      emissions due to changes in meteorological conditions and potential
      desertification.

PMID- 22859486
TI  - Aerial photographs reveal late-20th-century dynamic ice loss in northwestern
      Greenland.
AB  - Global warming is predicted to have a profound impact on the Greenland Ice Sheet
      and its contribution to global sea-level rise. Recent mass loss in the northwest
      of Greenland has been substantial. Using aerial photographs, we produced digital
      elevation models and extended the time record of recent observed marginal dynamic
      thinning back to the mid-1980s. We reveal two independent dynamic ice loss events
      on the northwestern Greenland Ice Sheet margin: from 1985 to 1993 and 2005 to
      2010, which were separated by limited mass changes. Our results suggest that the
      ice mass changes in this sector were primarily caused by short-lived dynamic ice
      loss events rather than changes in the surface mass balance. This finding
      challenges predictions about the future response of the Greenland Ice Sheet to
      increasing global temperatures.

PMID- 22859487
TI  - Cuckoos combat socially transmitted defenses of reed warbler hosts with a plumage
      polymorphism.
AB  - In predator-prey and host-parasite interactions, an individual's ability to
      combat an opponent often improves with experience--for example, by learning to
      identify enemy signals. Although learning occurs through individual experience,
      individuals can also assess threats from social information. Such recognition
      could promote the evolution of polymorphisms if socially transmitted defenses
      depend on enemy morph frequency. This would allow rare variants to evade
      detection. Female brood parasitic common cuckoos, Cuculus canorus, are either
      gray or rufous. The gray morph is a Batesian mimic whose hawk-like appearance
      deters host attack. Hosts reject this disguise through social learning,
      increasing their own defenses when they witness neighbors mobbing a cuckoo. Our
      experiments reveal that social learning is specific to the cuckoo morph that
      neighbors mob. Therefore, while neighbors alert hosts to local cuckoo activity,
      frequency-dependent social information selects for a cuckoo plumage polymorphism
      to thwart host detection. Our results suggest that selection for mimicry and
      polymorphisms comes not only from personal experience but also from social
      learning.

PMID- 22859488
TI  - Unraveling the life history of successful invaders.
AB  - Despite considerable current interest in biological invasions, the common life
      history characteristics of successful invaders remain elusive. The widely held
      hypothesis that successful invaders have high reproductive rates has received
      little empirical support; however, alternative possibilities are seldom
      considered. Combining a global comparative analysis of avian introductions (>2700
      events) with demographic models and phylogenetic comparative methods, we show
      that although rapid population growth may be advantageous during invasions under
      certain circumstances, more generally successful invaders are characterized by
      life-history strategies in which they give priority to future rather than current
      reproduction. High future breeding expectations reduce the costs of reproductive
      failure under uncertain conditions and increase opportunities to explore the
      environment and respond to novel ecological pressures.

PMID- 22859489
TI  - Opening and closing of the bacterial RNA polymerase clamp.
AB  - Using single-molecule fluorescence resonance energy transfer, we have defined
      bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription
      initiation and elongation. We find that the clamp predominantly is open in free
      RNAP and early intermediates in transcription initiation but closes upon
      formation of a catalytically competent transcription initiation complex and
      remains closed during initial transcription and transcription elongation. We show
      that four RNAP inhibitors interfere with clamp opening. We propose that clamp
      opening allows DNA to be loaded into and unwound in the RNAP active-center cleft,
      that DNA loading and unwinding trigger clamp closure, and that clamp closure
      accounts for the high stability of initiation complexes and the high stability
      and processivity of elongation complexes.

PMID- 22859490
TI  - How low can you go? Physical production mechanism of elephant infrasonic
      vocalizations.
AB  - Elephants can communicate using sounds below the range of human hearing
      ("infrasounds" below 20 hertz). It is commonly speculated that these
      vocalizations are produced in the larynx, either by neurally controlled muscle
      twitching (as in cat purring) or by flow-induced self-sustained vibrations of the
      vocal folds (as in human speech and song). We used direct high-speed video
      observations of an excised elephant larynx to demonstrate flow-induced self
      sustained vocal fold vibration in the absence of any neural signals, thus
      excluding the need for any "purring" mechanism. The observed physical principles
      of voice production apply to a wide variety of mammals, extending across a
      remarkably large range of fundamental frequencies and body sizes, spanning more
      than five orders of magnitude.

PMID- 22859491
TI  - Modulation of the cochaperone AHA1 regulates heat-shock protein 90 and
      endothelial NO synthase activation by vascular endothelial growth factor.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) signaling to endothelial NO
      synthase (eNOS) plays a central role in angiogenesis. In endothelial cells (ECs),
      heat-shock protein 90 (Hsp90) is also a regulator of eNOS activity. Our study is
      designed to determine whether modulation of the activator of Hsp90 ATPase 1
      (AHA1) regulates the function of Hsp90 in ECs. METHODS AND RESULTS: We show that
      eNOS phosphorylation on Ser-1179 after VEGF stimulation is significantly reduced
      in ECs transfected with a small interfering RNA against AHA1. Accordingly, VEGF
      stimulated NO production, endothelial permeability, cell migration, and EC
      invasion in Matrigel implants in mice are reduced in small interfering RNA
      against AHA1-treated conditions. Furthermore, the induction of eNOS association
      with Hsp90 after VEGF stimulation is decreased in AHA1-downregulated cells. We
      also demonstrate that modulation of Hsp90 activity by AHA1 regulates
      phosphorylation of Hsp90 on Tyr-300. Interestingly, the association of AHA1 with
      Hsp90 is increased after c-Src-mediated phosphorylation of Hsp90 on Tyr-300.
      Finally, we show that overexpression of AHA1 in ECs promotes association of eNOS
      and Hsp90, phosphorylation of Ser-1179 of eNOS, increases NO production, and cell
      migration. CONCLUSIONS: These results reveal that modulation of Hsp90 activity by
      AHA1 regulates VEGF signaling to eNOS and angiogenesis.

PMID- 22859492
TI  - P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation
      by N(epsilon)-lysine acetylation of contractile proteins.
AB  - OBJECTIVE: To address the role of epigenetic enzymes in the process of arterial
      vasorelaxation and nitrate tolerance, in vitro and in vivo experiments were
      performed in the presence or absence of glyceryl trinitrate (GTN) or histone
      deacetylases/histone acetylases modulators. METHODS AND RESULTS: In vitro single
      GTN administration rapidly increased cGMP synthesis and protein N(epsilon)-lysine
      acetylation in rat smooth muscle cells, including myosin light chain and smooth
      muscle actin. This phenomenon determined a decrease in myosin light chain
      phosphorylation and actomyosin formation. These effects were abolished by
      prolonged exposure to GTN and rescued by treatment with trichostatin A. In vivo,
      adult male rats were treated for 72 hours with subcutaneous injections of GTN
      alone or in combination with the histone deacetylases inhibitors trichostatin A,
      suberoylanilide hydroxamic acid, MS-27-275, or valproic acid. Ex vivo experiments
      performed on aortic rings showed that the effect of tolerance was reversed by all
      proacetylation drugs, including the p300/CREB binding protein-associated factor
      activator pentadecylidenemalonate 1b (SPV106). Any response to GTN was abolished
      by anacardic acid, a potent histone acetylases inhibitor. CONCLUSIONS: This study
      establishes the following points: (1) GTN treatment increases histone acetylases
      activity; (2) GTN-activated p300/CREB binding protein-associated factor increases
      protein N(epsilon)-lysine acetylation; (3) N(epsilon)-lysine acetylation of
      contractile proteins influences GTN-dependent vascular response. Hence,
      combination of epigenetic drugs and nitroglycerin may be envisaged as a novel
      treatment strategy for coronary artery disease symptoms and other cardiovascular
      accidents of ischemic origin.

PMID- 22859493
TI  - Diet modulates endogenous thrombin generation, a biological estimate of
      thrombosis risk, independently of the metabolic status.
AB  - OBJECTIVE: High endogenous thrombin potential (ETP) is associated with venous and
      arterial thrombosis. Better knowledge of environmental influences on ETP may help
      to prevent thrombosis. METHODS AND RESULTS: Weaning rats exhibited high ETP
      values that decreased in low-fat diet and remained elevated on high-fat diet. In
      adult rats, high-fat diet-induced ETP increase was independent of coagulation
      factors, obesity, and insulin resistance and negatively associated with
      polyunsaturated fatty acid levels. Switching from high-fat diet to low-fat diet
      reversed the procoagulant phenotype with a slower kinetic than the normalization
      of hyperinsulinemia. In humans, ETP was independent of body weight whereas it was
      negatively associated with nutritional markers such as the percentage of energy
      provided by proteins, the protein:fat ratio, circulating phenolic compounds, and
      omega-3 polyunsaturated fatty acid. A recommended 3-month healthy diet with
      reduced energy density, including lipids, decreased ETP (-21%; P<0.0001). Changes
      in ETP were not associated with body weight, insulin sensitivity, or coagulation
      factor variations, but correlated negatively with plasma docosahexaenoic acid, a
      nutritional status sensitive fatty acid, and compounds reflecting vegetable
      intake. CONCLUSIONS: Diet plays a pivotal role in regulating ETP, independently
      of obesity and insulin resistance. Global nutritional recommendations could be
      useful in primary prevention of venous thrombosis.

PMID- 22859494
TI  - The methyl xanthine caffeine inhibits DNA damage signaling and reactive species
      and reduces atherosclerosis in ApoE(-/-) mice.
AB  - OBJECTIVE: Caffeine remains one of the most widely consumed drugs in the world.
      Caffeine has multiple actions, including inhibition of the DNA damage response,
      and its metabolites, 1-methylxanthine and 1-methyluric acid, are potent
      antioxidants. Combined, these properties can exert direct effects on cell
      proliferation, cell death, inflammation, and DNA repair, all important processes
      that occur in atherosclerosis. METHODS AND RESULTS: We first examined the effects
      of caffeine on mouse vascular smooth muscle cells. Caffeine inhibited activation
      of the DNA damage response regulator ataxia telangiectasia mutated protein and
      its downstream targets. Caffeine delayed DNA repair, had a concentration
      dependent effect on cell proliferation, and protected against apoptosis. In vitro
      caffeine reduced oxygen consumption and decreased generation of reactive oxygen
      species. In vivo caffeine reduced DDR activation in vascular and nonvascular
      tissues, reduced reactive nitrogen species and serum levels of the DNA adduct 8
      oxo-guanine, and inhibited atherogenesis in fat-fed ApoE(-/-) mice. Reduction in
      atherosclerosis was independent of the effects on blood pressure and serum lipids
      but associated with reduced cell proliferation and ataxia telangiectasia mutated
      protein activation. CONCLUSIONS: The Methyl Xanthine caffeine inhibits the DNA
      damage response in vitro and in vivo, regulates both cell proliferation and
      apoptosis after DNA damage, inhibits reactive species, and reduces atherogenesis
      in ApoE(-/-) mice.

PMID- 22859495
TI  - Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic
      juice indicates the presence or emergence of pancreatic cysts.
AB  - OBJECTIVE: Pancreatic cysts are commonly detected in patients undergoing
      pancreatic imaging. Better approaches are needed to characterise these lesions.
      In this study we evaluated the utility of detecting mutant DNA in secretin
      stimulated pancreatic juice. DESIGN: Secretin-stimulated pancreatic juice was
      collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas
      Screening trials at five US academic medical centres. The study population
      included subjects with a familial predisposition to pancreatic cancer who
      underwent pancreatic screening, and disease controls with normal pancreata,
      chronic pancreatitis, sporadic intraductal papillary mucinous neoplasm (IPMN) or
      other neoplasms. Somatic GNAS mutations (reported prevalence ~ 66% of IPMNs) were
      measured using digital high-resolution melt-curve analysis and pyrosequencing.
      RESULTS: GNAS mutations were detected in secretin-stimulated pancreatic juice
      samples of 50 of 78 familial and sporadic cases of IPMN(s) (64.1%), 15 of 33
      (45.5%) with only diminutive cysts (<5 mm), but none of 57 disease controls. GNAS
      mutations were also detected in five of 123 screened subjects without a
      pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS
      mutations detected in baseline juice samples predicted subsequent emergence or
      increasing size of pancreatic cysts. CONCLUSION: Duodenal collections of secretin
      stimulated pancreatic juice from patients with IPMNs have a similar prevalence of
      mutant GNAS to primary IPMNs, indicating that these samples are an excellent
      source of mutant DNA from the pancreas. The detection of GNAS mutations before an
      IPMN is visible suggests that analysis of pancreatic juice has the potential to
      help in the risk stratification and surveillance of patients undergoing
      pancreatic screening.

PMID- 22859497
TI  - Prevalence of left ventricular dysfunction in a UK community sample of very old
      people: the Newcastle 85+ study.
AB  - OBJECTIVE: Heart failure (HF) prevalence rises sharply among those aged 85 years
      and over. Previous population based echocardiographic studies of left ventricular
      (LV) dysfunction, the substrate for HF, have included only small numbers in this
      age group. We used domiciliary echocardiography to estimate the prevalence of LV
      systolic and diastolic dysfunction in 87-89 year olds and the proportion
      remaining undiagnosed. DESIGN: Cross sectional analysis of data from Newcastle
      85+ Study. SETTING: Primary care, North-East England. PARTICIPANTS: 376 men and
      women aged 87-89 years. MEASURES: Domiciliary echocardiography was performed and
      LV systolic and diastolic function was graded. The presence of limiting dyspnoea
      was assessed by questionnaire. Previous diagnoses of HF were abstracted from
      general practice (GP) records. RESULTS: 32% of participants (119/376) had LV
      systolic dysfunction (ejection fraction (EF) <=50%) and a further 20% (75/376)
      had moderate or severe LV diastolic dysfunction with preserved EF. Both
      echocardiographic assessment of LV function and dyspnoea status were available in
      74% (278/376) of participants. Among these participants, limiting dyspnoea was
      present in approximately two thirds of those with significant (systolic or
      isolated moderate/severe diastolic) LV dysfunction. 84% (73/87) of participants
      with significant LV dysfunction and limiting dyspnoea did not have a pre-existing
      HF diagnosis in their GP records. Overall, 26% (73/278) of participants with both
      echocardiographic and dyspnoea data had undiagnosed, symptomatic, significant LV
      dysfunction. CONCLUSION: Significant systolic and diastolic LV dysfunction is
      much commoner in community dwelling 87-89 year olds than previous studies have
      suggested. The majority are both symptomatic and undiagnosed.

PMID- 22859498
TI  - Optimising the cost and delivery of HIV counselling and testing services in Kenya
      and Swaziland.
AB  - BACKGROUND: Approaches to HIV counselling and testing (HCT) within low-resource
      high HIV prevalence settings have shifted over the years from primarily client
      initiated approaches to provider initiated. As part of an ongoing programme
      science research agenda, we examine the relative costs of provider-initiated
      testing and counselling (PITC) services compared with voluntary counselling and
      testing (VCT) services in the same health facilities in two low-resource
      settings: Kenya and Swaziland. METHODS: Annual financial and economic costs and
      output measures were collected retrospectively from 28 health facilities. Total
      annual costs and average costs per client counselled and tested (C&T), and HIV
      positive clients identified, were estimated. RESULTS: VCT remains the predominant
      mode of HCT service delivery across both countries. However, unit cost per client
      C&T and per person testing HIV positive is lower for PITC than VCT across all
      facility types in Kenya, but the picture is mixed in Swaziland. Average cost per
      client C&T ranged from US $4.81 to US $6.11 in Kenya, US $6.92 to US $13.51 in
      Swaziland for PITC, and from US $5.05 to US $16.05 and US $8.68 to US $19.32 for
      VCT in Kenya and Swaziland, respectively. CONCLUSIONS: In the context of
      significant policy interest in optimising scarce HIV resources, this study
      demonstrates that there may be potential for substantial gains in efficiency in
      the provision of HCT services in both Kenya and Swaziland. However,
      considerations of how to deliver services efficiently need to be informed by
      local contextual factors, such as prevalence, service demand and availability of
      human resources.

PMID- 22859496
TI  - Randomised study comparing 48 and 96 weeks peginterferon alpha-2a therapy in
      genotype D HBeAg-negative chronic hepatitis B.
AB  - OBJECTIVE: Treatment with peginterferon alpha-2a (PegIFN) for 48 weeks is the
      standard of care for selected HBeAg-negative patients chronically infected with
      hepatitis B virus (HBV), but with limited treatment efficacy. A study was
      undertaken to investigate whether treatment extension to 96 weeks improves the
      outcome in this patient population. METHODS: 128 HBeAg-negative patients (120
      genotype D) were randomised to weekly 180 MUg PegIFN for 48 weeks (group A,
      n=51), 180 MUg PegIFN for 48 weeks followed by 135 MUg weekly for an additional
      48 weeks (group B, n=52) or 180 MUg PegIFN plus lamivudine (100 mg/day) for 48
      weeks then 135 MUg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine
      aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000
      IU/ml and HBsAg clearance at 48 weeks after treatment. RESULTS: Forty-eight weeks
      after treatment, six patients in group A and 13 in group B achieved alanine
      aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08),
      6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3
      achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0%
      vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent
      predictor of response, the combination with lamivudine did not improve responses.
      Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81)
      and were mostly due to PegIFN-related adverse events. CONCLUSIONS: In HBeAg
      negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96
      weeks was well tolerated and the post-treatment virological response improved
      significantly compared with 48 weeks of treatment. TRIAL REGISTRATION NUMBER:
      http://ClinicalTrials.gov registration number: NCT01095835.

PMID- 22859499
TI  - Incidence of acute hepatitis C virus infection among men who have sex with men
      with and without HIV infection: a systematic review.
AB  - BACKGROUND: A recent increase in reports of acute hepatitis C virus infection
      (HCV) in HIV-infected and HIV-uninfected men who have sex with men (MSM), with
      the sole risk factor being sexual exposure, has led to routine screening and
      targeted prevention requests for this population; current evidence for this
      necessity is unclear. OBJECTIVE: A systematic review was conducted to assess the
      incidence of HCV infection among studies conducted in HIV-positive and/or HIV
      negative MSM to explore the implications for routine HCV screening. DATA SOURCES:
      The MEDLINE, EMBASE and BIOSYS databases were searched for the period January
      2000 to May 2012, yielding 21 studies. Six conferences were hand-searched for the
      same period yielding four abstracts. STUDY SELECTION: Only studies in English
      presenting incidence rates of HCV and specifying HIV status were included. DATA
      ABSTRACTION: Data were abstracted by two authors using predefined data fields.
      The STROBE checklist was used to assess study quality. DATA SYNTHESIS: Data were
      divided into HIV-negative MSM and HIV-positive MSM subgroups, and HCV incidence
      density measurements were pooled. Using a DerSimonian-Laird random effects model,
      pooled incidence was 1.48/1000 person-years (95% CI 0.75 to 2.21) for the HIV
      negative MSM subgroup. The HIV-positive MSM subgroup was at 4.1 times higher risk
      of acquiring HCV at 6.08/1000 person-years (95% CI 5.18 to 6.99). Studies
      directly comparing subgroups estimated a pooled risk difference of 3.45/1000
      person-years (95% CI 1.63 to 5.27). CONCLUSION: HIV-positive MSM were at higher
      risk for acute HCV infection than HIV-negative MSM, substantiating the need for
      routine screening initiatives. Insufficient evidence exists to warrant routine
      screening of HIV-negative MSM, except on a case-by-case basis, such as high-risk
      sexual behaviour.

PMID- 22859501
TI  - SKEMPI: a Structural Kinetic and Energetic database of Mutant Protein
      Interactions and its use in empirical models.
AB  - MOTIVATION: Empirical models for the prediction of how changes in sequence alter
      protein-protein binding kinetics and thermodynamics can garner insights into many
      aspects of molecular biology. However, such models require empirical training
      data and proper validation before they can be widely applied. Previous databases
      contained few stabilizing mutations and no discussion of their inherent biases or
      how this impacts model construction or validation. RESULTS: We present SKEMPI, a
      database of 3047 binding free energy changes upon mutation assembled from the
      scientific literature, for protein-protein heterodimeric complexes with
      experimentally determined structures. This represents over four times more data
      than previously collected. Changes in 713 association and dissociation rates and
      127 enthalpies and entropies were also recorded. The existence of biases towards
      specific mutations, residues, interfaces, proteins and protein families is
      discussed in the context of how the data can be used to construct predictive
      models. Finally, a cross-validation scheme is presented which is capable of
      estimating the efficacy of derived models on future data in which these biases
      are not present. AVAILABILITY: The database is available online at
      http://life.bsc.es/pid/mutation_database/.

PMID- 22859500
TI  - Antiobesity activity of a sphingosine 1-phosphate analogue FTY720 observed in
      adipocytes and obese mouse model.
AB  - Higher levels of body fat are associated with an increased risk for development
      numerous adverse health conditions. FTY720 is an immune modulator and a synthetic
      analogue of sphingosine 1-phosphate (S1P), activated S1P receptors and is
      effective in experimental models of transplantation and autoimmunity. Whereas
      immune modulation by FTY720 has been extensively studied, other actions of FTY720
      are not well understood. Here we describe a novel role of FTY720 in the
      prevention of obesity, involving the regulation of adipogenesis and lipolysis in
      vivo and in vitro. Male C57B/6J mice were fed a standard diet or a high fat diet
      (HFD) without or with FTY720 (0.04 mg/kg, twice a week) for 6 weeks. The HFD
      induced an accumulation of large adipocytes, down-regulation of phosphorylated
      AMP-activated protein kinase alpha (p-AMPKalpha) and Akt (p-Akt); down-regulation
      of hormone- sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and
      perilipin mRNA as well as up-regulation of phosphorylated HSL (p-HSL, Ser563) and
      glycogen synthase kinase 3 alpha/beta (p-GSK3alpha/beta). All these effects were
      blunted by FTY720 treatment, which inhibited adipogenesis and promoted lipolysis.
      Also, FTY720 significantly decreased lipid accumulation in maturing
      preadipocytes. FTY720 down-regulated the transcriptional levels of the PPARgamma,
      C/EBPalpha and adiponectin, which are markers of adipogenic differentiation.
      FTY720 significantly increased the release of glycerol and the expression of the
      HSL, ATGL and perilipin, which are regulators of lipolysis. These results show
      that FTY720 prevented obesity by modulating adipogenesis and lipolysis, and
      suggest that FTY720 is used for the treatment of obesity.

PMID- 22859502
TI  - A robust approach to extract biomedical events from literature.
AB  - MOTIVATION: The abundance of biomedical literature has attracted significant
      interest in novel methods to automatically extract biomedical relations from the
      literature. Until recently, most research was focused on extracting binary
      relations such as protein-protein interactions and drug-disease relations.
      However, these binary relations cannot fully represent the original biomedical
      data. Therefore, there is a need for methods that can extract fine-grained and
      complex relations known as biomedical events. RESULTS: In this article we propose
      a novel method to extract biomedical events from text. Our method consists of two
      phases. In the first phase, training data are mapped into structured
      representations. Based on that, templates are used to extract rules
      automatically. In the second phase, extraction methods are developed to process
      the obtained rules. When evaluated against the Genia event extraction abstract
      and full-text test datasets (Task 1), we obtain results with F-scores of 52.34
      and 53.34, respectively, which are comparable to the state-of-the-art systems.
      Furthermore, our system achieves superior performance in terms of computational
      efficiency. AVAILABILITY: Our source code is available for academic use at
      http://dl.dropbox.com/u/10256952/BioEvent.zip.

PMID- 22859503
TI  - Epistatic dissection of laminin-receptor interactions in dystrophic zebrafish
      muscle.
AB  - Laminins form essential components of the basement membrane and are integral to
      forming and maintaining muscle integrity. Mutations in the human Laminin-alpha2
      (LAMA2) gene result in the most common form of congenital muscular dystrophy,
      MDC1A. We have previously identified a zebrafish model of MDC1A called candyfloss
      (caf), carrying a loss-of-function mutation in the zebrafish lama2 gene. In the
      skeletal muscle, laminins connect the muscle cell to the extracellular matrix
      (ECM) by binding either dystroglycan or integrins at the cell membrane. Through
      epistasis experiments, we have established that both adhesion systems
      individually contribute to the maintenance of fibre adhesions and exhibit muscle
      detachment phenotypes. However, larval zebrafish in which both adhesion systems
      are simultaneously genetically inactivated possess a catastrophic failure of
      muscle attachment that is far greater than a simple addition of individual
      phenotypes would predict. We provide evidence that this is due to other crucial
      laminins present in addition to Lama2, which aid muscle cell attachments and
      integrity. We have found that lama1 is important for maintaining attachments,
      whereas lama4 is localized and up-regulated in damaged fibres, which appears to
      contribute to fibre survival. Importantly, our results show that endogenous
      secretion of laminins from the surrounding tissues has the potential to reinforce
      fibre attachments and strengthen laminin-ECM attachments. Collectively these
      findings provide a better understanding of the cellular pathology of MDC1A and
      help in designing effective therapies.

PMID- 22859504
TI  - Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic
      neurons in the nigrostriatal circuit.
AB  - Mitochondria continually undergo fusion and fission, and these dynamic processes
      play a major role in regulating mitochondrial function. Studies of several genes
      associated with familial Parkinson's disease (PD) have implicated aberrant
      mitochondrial dynamics in the disease pathology, but the importance of these
      processes in dopaminergic neurons remains poorly understood. Because the
      mitofusins Mfn1 and Mfn2 are essential for mitochondrial fusion, we deleted these
      genes from a subset of dopaminergic neurons in mice. Loss of Mfn2 results in a
      movement defect characterized by reduced activity and rearing. In open field
      tests, Mfn2 mutants show severe, age-dependent motor deficits that can be rescued
      with L-3,4 dihydroxyphenylalanine. These motor deficits are preceded by the loss
      of dopaminergic terminals in the striatum. However, the loss of dopaminergic
      neurons in the midbrain occurs weeks after the onset of these motor and striatal
      deficits, suggesting a retrograde mode of neurodegeneration. In our conditional
      knockout strategy, we incorporated a mitochondrially targeted fluorescent
      reporter to facilitate tracking of mitochondria in the affected neurons. Using an
      organotypic slice culture system, we detected fragmented mitochondria in the soma
      and proximal processes of these neurons. In addition, we found markedly reduced
      mitochondrial mass and transport, which may contribute to the neuronal loss.
      These effects are specific for Mfn2, as the loss of Mfn1 yielded no corresponding
      defects in the nigrostriatal circuit. Our findings indicate that perturbations of
      mitochondrial dynamics can cause nigrostriatal defects and may be a risk factor
      for the neurodegeneration in PD.

PMID- 22859505
TI  - The galactocerebrosidase enzyme contributes to maintain a functional neurogenic
      niche during early post-natal CNS development.
AB  - We report a novel role for the lysosomal galactosylceramidase (GALC), which is
      defective in globoid cell leukodystrophy (GLD), in maintaining a functional post
      natal subventricular zone (SVZ) neurogenic niche. We show that proliferation/self
      renewal of neural stem cells (NSCs) and survival of their neuronal and
      oligodendroglial progeny are impaired in GALC-deficient mice. Using drugs to
      modulate inflammation and gene transfer to rescue GALC expression and activity,
      we show that lipid accumulation resulting from GALC deficiency acts as a cell
      autonomous pathogenic stimulus in enzyme-deficient NSCs and progeny before
      upregulation of inflammatory markers, which later sustain a non-cell-autonomous
      dysfunction. Importantly, we provide evidence that supply of functional GALC
      provided by neonatal intracerebral transplantation of NSCs ameliorates the
      functional impairment in endogenous SVZ cells. Insights into the mechanism/s
      underlying GALC-mediated regulation of early post-natal neurogenic niches improve
      our understanding of the multi-component pathology of GLD. The occurrence of a
      restricted period of SVZ neurogenesis in infancy supports the implications of our
      study for the development of therapeutic strategies to treat this severe
      pediatric neurodegenerative disorder.

PMID- 22859506
TI  - Legume receptors perceive the rhizobial lipochitin oligosaccharide signal
      molecules by direct binding.
AB  - Lipochitin oligosaccharides called Nod factors function as primary rhizobial
      signal molecules triggering legumes to develop new plant organs: root nodules
      that host the bacteria as nitrogen-fixing bacteroids. Here, we show that the
      Lotus japonicus Nod factor receptor 5 (NFR5) and Nod factor receptor 1 (NFR1)
      bind Nod factor directly at high-affinity binding sites. Both receptor proteins
      were posttranslationally processed when expressed as fusion proteins and
      extracted from purified membrane fractions of Nicotiana benthamiana or
      Arabidopsis thaliana. The N-terminal signal peptides were cleaved, and NFR1
      protein retained its in vitro kinase activity. Processing of NFR5 protein was
      characterized by determining the N-glycosylation patterns of the ectodomain. Two
      different glycan structures with identical composition, Man(3)XylFucGlcNAc(4),
      were identified by mass spectrometry and located at amino acid positions N68 and
      N198. Receptor-ligand interaction was measured by using ligands that were labeled
      or immobilized by application of chemoselective chemistry at the anomeric center.
      High-affinity ligand binding was demonstrated with both solid-phase and free
      solution techniques. The K(d) values obtained for Nod factor binding were in the
      nanomolar range and comparable to the concentration range sufficient for
      biological activity. Structure-dependent ligand specificity was shown by using
      chitin oligosaccharides. Taken together, our results suggest that ligand
      recognition through direct ligand binding is a key step in the receptor-mediated
      activation mechanism leading to root nodule development in legumes.

PMID- 22859507
TI  - Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian
      endometriosis.
AB  - BACKGROUND: Current non-invasive diagnostic methods for endometriosis lack
      sensitivity and specificity. In search for new diagnostic biomarkers for ovarian
      endometriosis, we used a hypothesis-generating targeted metabolomics approach.
      METHODS: In a case-control study, we collected plasma of study participants and
      analysed their metabolic profiles. We selected a group of 40 patients with
      ovarian endometriosis who underwent laparoscopic surgery and a control group of
      52 healthy women who underwent sterilization at the University Clinical Centre
      Ljubljana, Slovenia. Over 140 targeted analytes included glycerophospholipids,
      sphingolipids and acylcarnitines. The analytes were quantified by electrospray
      ionization tandem mass spectrometry. For assessing the strength of association
      between the metabolite or metabolite ratios and the disease, we used crude and
      adjusted odds ratios. A stepwise logistic regression procedure was used for
      selecting the best combination of biomarkers. RESULTS: Eight lipid metabolites
      were identified as endometriosis-associated biomarkers due to elevated levels in
      patients compared with controls. A model containing hydroxysphingomyelin SMOH
      C16:1 and the ratio between phosphatidylcholine PCaa C36:2 to ether-phospholipid
      PCae C34:2, adjusted for the effect of age and the BMI, resulted in a sensitivity
      of 90.0%, a specificity of 84.3% and a ratio of the positive likelihood ratio to
      the negative likelihood ratio of 48.3. CONCLUSIONS: Our results suggest that
      endometriosis is associated with elevated levels of sphingomyelins and
      phosphatidylcholines, which might contribute to the suppression of apoptosis and
      affect lipid-associated signalling pathways. Our findings suggest novel potential
      routes for therapy by specifically blocking highly up-regulated isoforms of
      phosphpolipase A2 and lysophosphatidylcholine acyltransferase 4.

PMID- 22859508
TI  - Disclosure behaviour and intentions among 111 couples following treatment with
      oocytes or sperm from identity-release donors: follow-up at offspring age 1-4
      years.
AB  - STUDY QUESTION: Do heterosexual parents of young children following oocyte
      donation (OD) and sperm donation (SD) tell or intend to tell their offspring
      about the way he/she was conceived? SUMMARY ANSWER: Following successful
      treatment with oocytes or sperm from identity-release donors in Sweden, almost
      all heterosexual couples intend to tell their offspring about the way he/she was
      conceived and some start the information-sharing process very early. WHAT IS
      KNOWN AND WHAT THIS PAPER ADDS: Although the Swedish legislation on identity
      release gamete donors has been in effect since 1985, there is a discrepancy
      between the behaviour of donor-insemination parents and the legal intention that
      offspring be informed about their genetic origin. The present study contributes
      data on a relatively large sample of oocyte and sperm recipient couples' intended
      compliance with the Swedish legislation.    DESIGN AND DATA COLLECTION METHOD:  
      The present study constitutes a follow-up assessment of heterosexual couples who
      had given birth to a child following treatment with donated oocytes. Data
      collection was performed during 2007-2011; participants individually completed a
      questionnaire when the child was between 1 and 4 years of age. PARTICIPANTS AND
      SETTING: The present study is part of the Swedish Study on Gamete Donation, a
      prospective longitudinal cohort study including all fertility clinics performing
      gamete donation in Sweden. For children conceived via OD, 107 individuals
      (including 52 couples and 3 individuals) agreed to participate (73% response).
      For children conceived via SD, the response rate was 70% (n = 122 individuals,
      including 59 couples and 4 individuals). Mean age of participants was 34 years
      (SD 4.4) and they reported a high level of education. MAIN RESULTS: The majority
      of participants (78%) planned to tell the child about the donation, 16% had
      already started the information-sharing process and 6% planned not to tell their
      child about the donation or were undecided. Many were unsure about a suitable
      time to start the disclosure process and desired more information about
      strategies and tools for information sharing. Agreement on disclosure to
      offspring within the couple was related to the quality of the partner
      relationship.    BIAS AND GENERALIZABILITY:   There is a risk of selection bias,
      with gamete recipients preferring secrecy and non-disclosure declining study
      participation. The results may be regarded as partly generalizable to
      heterosexual couples with young children following treatment with gametes from
      legislatively mandated identity-release donors in an established donor programme.
      STUDY FUNDING/COMPETING INTERESTS: Study funding by Merck Serono, The Swedish
      Research Council and The Family Planning Fund in Uppsala. No conflicts of
      interest to declare.

PMID- 22859509
TI  - Early clinical implications of microalbuminuria in patients with acute ischaemic
      stroke.
AB  - BACKGROUND: Microalbuminuria is thought to be independently associated with an
      increased risk of, and mortality from, stroke. However, no studies have shown
      whether microalbuminuria is associated with the early clinical outcomes of acute
      ischaemic stroke. Therefore we investigated whether this. We also looked at
      radiological outcomes in stroke patients with microalbuminuria. METHODS: This was
      a retrospective study of patients with ischaemic stroke (within 72 h of symptom
      onset) who had been consecutively admitted to the Cerebrovascular Center at
      Chonnam National University Hospital between May 2010 and February 2011. Early
      clinical outcomes were assessed by early neurological deterioration (END) and
      modified Rankin Scale score >2 at discharge. In addition, early radiological
      outcomes were assessed from haemorrhagic transformation (HT) and lesion changes
      on follow-up diffusion-weighted imaging. We categorised a urine
      albumin/creatinine ratio of <=30 mg albumin/g creatinine as normal and 30-300 mg
      albumin/g creatinine as microalbuminuria. RESULTS: 139 of 361 patients (38.5%)
      had microalbuminuria. In multivariate analysis, microalbuminuria was
      independently associated with END and HT. Furthermore, there were significant
      relationships between urinary albumin/creatinine ratio and white matter
      hyperintensity (WMH) grades (31.78 mg albumin/g creatinine for no WMH, 48.41 for
      grade 1, 64.29 for grade 2, and 44.16 for grade 3; p=0.004) and the types of HT
      (37.43 mg albumin/g creatinine for no HT, 71.41 for HI, and 131.63 for PH;
      p<0.001). CONCLUSION: In the early phase of ischaemic stroke, patients with
      microalbuminuria were associated with worse clinical and radiological outcomes
      (END, HT and lesion changes on follow-up diffusion-weighted imaging) than those
      without.

PMID- 22859511
TI  - Is computed tomography follow-up of patients after lobectomy for non-small cell
      lung cancer of benefit in terms of survival?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was whether following up patients
      after lobectomy for non-small cell lung cancer (NSCLC) with computed tomography
      (CT) scanning is of benefit in terms of survival. Altogether, 448 papers were
      found using the reported search, of which five represented the best evidence to
      answer the clinical question and three provided supporting evidence. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. There is no general
      consensus in the literature. From the limited number of papers that address the
      effect of CT follow-up on survival following surgery for NSCLC, three showed that
      CT scanning may improve the survival of patients by detecting local and distant
      recurrences at an earlier stage when the patient is asymptomatic. One paper
      showed that detection by the use of low-dose CT or simultaneous chest CT plus
      positron emission tomography-CT led to a longer duration of survival compared
      with detection by clinical suspicion (2.1 +/- 0.3 vs 3.6 +/- 0.2 years, p =
      0.002). However, two papers broadly showed that follow-up with CT does not
      improve survival outcomes regardless of the site of recurrence. One such study
      showed that there was no clinically significant difference in survival whether
      patients were followed up using a strict CT protocol compared with a symptom
      based follow-up (median survival after recurrence: strict 7.9 months, symptom
      based 6.6 months, p = 0.219). The remaining papers supported the use of CT as a
      screening tool for recurrence but did not comment directly on survival. Owing to
      the limited and contradictory evidence, there is a need for an randomized
      controlled trial to assess the survival outcomes of patients followed up with a
      CT screening protocol vs a symptom-based follow-up.

PMID- 22859512
TI  - Thymic haemangioma presenting with a left innominate vein aneurysm: insight into
      the aetiology.
AB  - Thymic haemangiomas and innominate vein aneurysms are rare with only 7 and 19
      previous cases, respectively, reported in the medical literature. The aetiology
      of an innominate vein aneurysm remains unclear and there is no previous report of
      tumour involvement. We present the case of a 27-year old male with concomitant
      mediastinal tumour and innominate vein aneurysm who underwent surgical treatment.
      The tumour intruded into the lower section of the innominate vein, thus causing
      aneurysmal dilation. Pathologically, the tumour was diagnosed as a thymic
      cavernous haemangioma involving the left innominate vein. This is the first case
      of a thymic haemangioma presenting with an innominate vein aneurysm, and suggests
      that tumours may be involved in the aetiology of innominate vein aneurysms.

PMID- 22859513
TI  - A single papillary muscle with chordal rupture in an adult.
AB  - A single papillary muscle (SPM) is a rare anomaly in normal adults. It is
      sometimes associated with a complete common atrioventricular canal. Chordal
      rupture combined with a single papillary muscle in an adult has not been
      reported. We repaired the mitral valve with chordal replacement, although this
      was technically difficult, because the decision to place an artificial chordal
      attachment on the papillary muscle plays an important role. This report presents
      successful chordal replacement and band annuloplasty in a case of chordal rupture
      with a single papillary muscle. A surgical tip for chordal replacement with a
      single papillary muscle is to suture artificial chords on the same side of the
      SPM head as the affected side of the mitral valve, considering the direction of
      pull of the artificial chords.

PMID- 22859514
TI  - Prediction of functional outcome at six months following total hip arthroplasty.
AB  - BACKGROUND: Recovery of function such as the ability to walk without an assistive
      device after total hip arthroplasty (THA) is not always automatic. OBJECTIVE:
      This study investigated whether predetermined variables could be used to identify
      patients who might have functional limitations at 6 months following THA. DESIGN:
      A prospective, observational cohort design was used. METHOD: Demographics and
      baseline measures, including age, sex, and preoperative Lower Extremity
      Functional Scale (LEFS) score, were collected 1 to 3 weeks prior to surgery from
      40 participants who were scheduled to undergo THA. Six weeks after surgery, a
      second LEFS score was recorded along with each participant's body mass index and
      the THA procedure performed; walking speed and balance also were assessed at this
      time using the 10-Meter Walk Test, the Timed "Up & Go" Test, and the Functional
      Reach Test. At 6 months following surgery, each participant's functional outcome
      was determined from the final LEFS score and the need for an assistive device.
      Classification and regression tree (CART) analyses and logistic regression were
      used to establish which of the variables could predict outcome at 6 months.
      RESULTS: Body mass index, sex, and age were identified by CART analysis as
      predictors to classify participants who did not reach successful outcome status.
      Logistic regression revealed that sex (female) was the only individual variable
      that predicted outcome at 6 months. Walking speed was the only performance
      variable identified as a predictor for outcome using CART analysis. LIMITATIONS:
      Only a limited number of variables were observed due to the small sample size.
      CONCLUSION: It is possible to identify those patients who are at risk for an
      unsuccessful outcome through the use of variables such as body mass index, age,
      and sex.

PMID- 22859515
TI  - Seasonal variation in cardiovascular disease risk factors in a subarctic
      population: the Tromso Study 1979-2008.
AB  - BACKGROUND: Seasonal changes in cardiovascular disease (CVD) risk factors may be
      due to exposure to seasonal environmental variables like temperature and acute
      infections or seasonal behavioural patterns in physical activity and diet.
      Investigating the seasonal pattern of risk factors should help determine the
      causes of the seasonal pattern in CVD. Few studies have investigated the seasonal
      variation in risk factors using repeated measurements from the same individual,
      which is important as individual and population seasonal patterns may differ.
      METHODS: The authors investigated the seasonal pattern in systolic and diastolic
      blood pressure, heart rate, body weight, total cholesterol, triglycerides, high
      density lipoprotein cholesterol, C reactive protein and fibrinogen. Measurements
      came from 38 037 participants in the population-based cohort, the Tromso Study,
      examined up to eight times from 1979 to 2008. Individual and population seasonal
      patterns were estimated using a cosinor in a mixed model. RESULTS: All risk
      factors had a highly statistically significant seasonal pattern with a peak time
      in winter, except for triglycerides (peak in autumn), C reactive protein and
      fibrinogen (peak in spring). The sizes of the seasonal variations were clinically
      modest. CONCLUSIONS: Although the authors found highly statistically significant
      individual seasonal patterns for all risk factors, the sizes of the changes were
      modest, probably because this subarctic population is well adapted to a harsh
      climate. Better protection against seasonal risk factors like cold weather could
      help reduce the winter excess in CVD observed in milder climates.

PMID- 22859516
TI  - Predictive risk algorithms in a population setting: an overview.
AB  - BACKGROUND: The widespread use of risk algorithms in clinical medicine is
      testimony to how they have helped transform clinical decision-making. Risk
      algorithms have a similar but underdeveloped potential to support decision-making
      for population health. OBJECTIVE: To describe the role of predictive risk
      algorithms in a population setting. METHODS: First, predictive risk algorithms
      and how clinicians use them are described. Second, the population uses of risk
      algorithms are described, highlighting the strengths of risk algorithms for
      health planning. Lastly, the way in which predictive risk algorithms are
      developed is discussed briefly and a guide for algorithm assessment in population
      health presented. CONCLUSION: For the past 20 years, absolute and baseline risk
      has been a cornerstone of population health planning. The most accurate and
      discriminating method to generate such estimates is the use of multivariable risk
      algorithms. Routinely collected data can be used to develop algorithms with
      characteristics that are well suited to health planning and such data are
      increasingly available. The widespread use of risk algorithms in clinical
      medicine is testimony to how they have helped transform clinical decision-making.
      Risk algorithms have a similar but underdeveloped potential to support decision
      making for population health.

PMID- 22859517
TI  - Excess suicides and attempted suicides in Italy attributable to the great
      recession.

PMID- 22859518
TI  - Fukushima nuclear power plant accident: issues on radiation monitoring and its
      relation to public health.

PMID- 22859519
TI  - Sperm proteasome degrades egg envelope glycoprotein ZP1 during fertilization of
      Japanese quail (Coturnix japonica).
AB  - At the time of fertilization, the extracellular matrix surrounding avian oocytes,
      termed the perivitelline membrane (pvm), is hydrolyzed by a sperm-borne protease,
      although the actual protease that is responsible for the digestion of the pvm
      remains to be identified. Here, we show evidence that the ubiquitin-proteasome
      system is functional in the fertilization of Japanese quail. The activities for
      the induction of the acrosome reaction and binding to ZP3 as revealed by ligand
      blotting of purified serum ZP1 are similar to those of pvm ZP1. Western blot
      analysis of purified ZP1 and ZP3 by the use of the anti-ubiquitin antibody showed
      that only pvm ZP1 was reactive to the antibody. In vitro penetration assay of the
      sperm on the pvm indicated that fragments of ZP1 and intact ZP3 were released
      from the pvm. Western blot analysis using the anti-20S proteasome antibody and
      ultrastructural analysis showed that immunoreactive proteasome was localized in
      the acrosomal region of the sperm. Inclusion of specific proteasome inhibitor
      MG132 in the incubation mixture, or depletion of extracellular ATP by the
      addition of apyrase, efficiently suppressed the sperm perforation of the pvm.
      These results demonstrate for the first time that the sperm proteasome is
      important for fertilization in birds and that the extracellular ubiquitination of
      ZP1 might occur during its transport via blood circulation.

PMID- 22859520
TI  - Low abundance plasma proteins in labour.
AB  - Every year, millions of births worldwide are complicated by prematurity or
      difficult post-term deliveries, resulting in a high incidence of perinatal
      mortality and morbidity. Our poor understanding of human parturition is a key
      reason for our inability to improve the management of preterm and post-term
      birth. In this study, we used proteomic techniques to look into protein changes
      in placental blood plasma obtained from women before or after spontaneous or
      induced labour, with vaginal or caesarean section deliveries. Our aim was to
      understand the basic mechanisms of human parturition regardless of whether the
      signals that trigger labour are of maternal and/or fetal origin. We found
      proteins from 33 genes with significantly altered expression profiles in relation
      to mode of labour and delivery. Most changes in labour occurred in proteins
      associated with 'immune and defence responses'. Although the signal transduction
      and regulation of these pathways varied among modes of delivery, hepatocyte
      nuclear factor 1 homeobox A emerged as a shared protein in the mechanism of
      labour. Moreover, several apolipoproteins such as apolipoprotein A-IV and APOE
      were found to change with labour, and these changes were also confirmed in
      maternal plasma. This study has identified significant protein changes in
      placental intervillous plasma with labour and has revealed several pathways
      related to human parturition.

PMID- 22859521
TI  - Environment or host?: A case-control study of risk factors for Mycobacterium
      avium complex lung disease.
AB  - RATIONALE: Mycobacterium avium complex lung disease is an increasingly common and
      chronically debilitating problem. Several host traits have been suggested or
      confirmed as risk factors. Potential environmental and behavioral risk factors
      have also been proposed. Few have been evaluated in comparative studies.
      OBJECTIVES: To determine if aerosol-generating activities in the home and garden,
      features of the home water supply, or several pulmonary and immune-compromising
      conditions are associated with Mycobacterium avium complex lung disease. METHODS:
      Cases were recruited from academic medical centers and by informal referrals from
      nonuniversity practices in Washington and Oregon. Control subjects were recruited
      by random-digit dialing and matched to cases by age, sex, and partial telephone
      number. Associations were measured as odds ratios (OR) estimated using
      conditional logistic regression. MEASUREMENTS AND MAIN RESULTS: Known and
      potential risk factors were measured by in-home interview. Fifty-two matched
      pairs were studied. Six of 12 examined host traits were associated with disease,
      including history of chronic obstructive pulmonary disease (OR, 10; 95%
      confidence interval [CI], 1.2-80), pneumonia hospitalization (OR, 3.4; 95% CI,
      1.1-11), and steroid use (OR, 8; 95% CI, 1.6-41). In contrast, 11 of the 14
      aerosol-generating activities and all five features of home water supply studied
      bore little or no association with disease. CONCLUSIONS: Aerosol-generating
      activities seem not to be risk factors for Mycobacterium avium complex lung
      disease in HIV-negative adults, but prior lung disease and immune-suppressing
      drugs seem to be associated with susceptibility.

PMID- 22859522
TI  - Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and
      humans.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating disease
      characterized by epithelial phenotypic changes and fibroblast activation. Based
      on the temporal heterogeneity of IPF, we hypothesized that hyperplastic alveolar
      epithelial cells regulate the fibrotic response. OBJECTIVES: To identify novel
      mediators of fibrosis comparing the transcriptional signature of hyperplastic
      epithelial cells and conserved epithelial cells in the same lung. METHODS: Laser
      capture microscope and microarrays analysis were used to identify differentially
      expressed genes in IPF lungs. Bleomycin-induced lung fibrosis was evaluated in
      Mmp19-deficient and wild-type (WT) mice. The role of matrix metalloproteinase
      (MMP)-19 was additionally studied by transfecting the human MMP19 in alveolar
      epithelial cells. MEASUREMENTS AND MAIN RESULTS: Laser capture microscope
      followed by microarray analysis revealed a novel mediator, MMP-19, in
      hyperplastic epithelial cells adjacent to fibrotic regions. Mmp19(-/-) mice
      showed a significantly increased lung fibrotic response to bleomycin compared
      with WT mice. A549 epithelial cells transfected with human MMP19 stimulated wound
      healing and cell migration, whereas silencing MMP19 had the opposite effect. Gene
      expression microarray of transfected A549 cells showed that PTGS2 (prostaglandin
      endoperoxide synthase 2) was one of the highly induced genes. PTGS2 was
      overexpressed in IPF lungs and colocalized with MMP-19 in hyperplastic epithelial
      cells. In WT mice, PTGS2 was significantly increased in bronchoalveolar lavage
      and lung tissues after bleomycin-induced fibrosis, but not in Mmp19(-/-) mice.
      Inhibition of Mmp-19 by siRNA resulted in inhibition of Ptgs2 at mRNA and protein
      levels. CONCLUSIONS: Up-regulation of MMP19 induced by lung injury may play a
      protective role in the development of fibrosis through the induction of PTGS2.

PMID- 22859523
TI  - beta-adrenergic sweat secretion as a diagnostic test for cystic fibrosis.
AB  - RATIONALE: beta-Adrenergically induced sweat secretion offers an expedient method
      to assess native cystic fibrosis transmembrane conductance regulator (CFTR)
      secretory function in vivo. OBJECTIVES: To evaluate the sensitivity, specificity,
      and reliability of a test based on the activity and secretory function of CFTR in
      the sweat gland. METHODS: Primary and validation trials with prospectively
      ascertained healthy control subjects, obligate heterozygotes, and patients with a
      CFTR-related disorder and CF (pancreatic sufficient and insufficient).
      MEASUREMENTS AND MAIN RESULTS: Diagnostic accuracy and reliability of beta
      adrenergic sweat secretory rates using an evaporimeter was assessed and compared
      with sweat chloride concentrations. The cholinergically stimulated mean sweat
      rate did not differ among groups. The mean maximal beta-adrenergically stimulated
      sweat rate in heterozygotes was about half the rate of healthy control subjects,
      and completely absent in pancreatic-insufficient patients with CF and pancreatic
      sufficient patients with CF (P < 0.0001). Subjects with a CFTR-related disorder
      showed reduced or absent beta-adrenergic sweat secretion. The beta-adrenergic
      secretory response demonstrated high diagnostic accuracy (area under a
      characteristic receiver-operator curve = 0.99; 95% confidence interval, 0.97
      1.00) and reliability (intraclass correlation, 0.90; 95% confidence interval,
      0.81-0.95). The diagnostic cutoff level for CF, derived from the primary trial,
      correctly identified all control subjects, heterozygotes, and patients with CF in
      the validation cohort, whereas concurrent sweat chloride measurements
      misclassified one heterozygote and five subjects with CF. The cholinergic and
      beta-adrenergic sweat secretion rates were lower in women compared with men (P <
      0.001). CONCLUSIONS: beta-Adrenergic sweat secretion rate determined by
      evaporimetry is an accurate and reliable technique to assess different levels of
      CFTR function and to identify patients with CF.

PMID- 22859524
TI  - End-of-life care in the intensive care unit: can we simultaneously increase
      quality and reduce costs?
AB  - The incidence and costs of critical illness are increasing in the United States
      at a time when there is a focus both on limiting the rising costs of healthcare
      and improving the quality of end-of-life care. More than 25% of healthcare costs
      are spent in the last year of life, and approximately 20% of deaths occur in the
      intensive care unit (ICU). Consequently, there has been speculation that end-of
      life care in the ICU represents an important target for cost savings. It is
      unclear whether efforts to improve end-of-life care in the ICU could
      significantly reduce healthcare costs. Here, we summarize recent studies
      suggesting that important opportunities may exist to improve quality and reduce
      costs through two mechanisms: advance care planning for patients with life
      limiting illness and use of time-limited trials of ICU care for critically ill
      patients. The goal of these approaches is to ensure patients receive the
      intensity of care that they would choose at the end of life, given the
      opportunity to make an informed decision. Although these mechanisms hold promise
      for increasing quality and reducing costs, there are few clearly described,
      effective methods to implement these mechanisms in routine clinical practice. We
      believe basic science in communication and decision making, implementation
      research, and demonstration projects are critically important if we are to
      translate these approaches into practice and, in so doing, provide high-quality
      and patient-centered care while limiting rising healthcare costs.

PMID- 22859527
TI  - Management of rheumatoid arthritis 2012: a Canadian state of the art.

PMID- 22859525
TI  - Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary
      arterial hypertension.
AB  - RATIONALE: Patients with idiopathic pulmonary arterial hypertension (iPAH) often
      have a low cardiac output. To compensate, neurohormonal systems such as the renin
      angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up
      regulated, but this may have long-term negative effects on the progression of
      iPAH. OBJECTIVES: Assess systemic and pulmonary RAAS activity in patients with
      iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.
      METHODS: We collected 79 blood samples from 58 patients with iPAH in the VU
      University Medical Center Amsterdam (between 2004 and 2010) to determine systemic
      RAAS activity. MEASUREMENTS AND MAIN RESULTS: We observed increased levels of
      renin, angiotensin (Ang)I, and AngII, which were associated with disease
      progression (P < 0.05) and mortality (P < 0.05). To determine pulmonary RAAS
      activity, lung specimens were obtained from patients with iPAH (during lung
      transplantation, n = 13) and control subjects (during lobectomy or pneumonectomy
      for cancer, n = 14). Local RAAS activity in pulmonary arteries of patients with
      iPAH was increased, demonstrated by elevated angiotensin-converting enzyme
      activity in pulmonary endothelial cells and increased AngII type 1 (AT(1))
      receptor expression and signaling. In addition, local RAAS up-regulation was
      associated with increased pulmonary artery smooth muscle cell proliferation via
      enhanced AT(1) receptor signaling in patients with iPAH compared with control
      subjects. Finally, to determine the therapeutic potential of RAAS activity, we
      assessed the chronic effects of an AT(1) receptor antagonist (losartan) in the
      monocrotaline PAH rat model (60 mg/kg). Losartan delayed disease progression,
      decreased right ventricular afterload and pulmonary vascular remodeling, and
      restored right ventricular-arterial coupling in rats with PAH. CONCLUSIONS:
      Systemic and pulmonary RAAS activities are increased in patients with iPAH and
      are associated with increased pulmonary vascular remodeling. Chronic inhibition
      of RAAS by losartan is beneficial in experimental PAH.

PMID- 22859528
TI  - Infusion reactions related to infliximab therapy are not usually associated with
      drug discontinuation.

PMID- 22859529
TI  - Classification criteria and diagnostic tests for vasculitides.

PMID- 22859526
TI  - Early intensive care sedation predicts long-term mortality in ventilated
      critically ill patients.
AB  - RATIONALE: Choice and intensity of early (first 48 h) sedation may affect short-
      and long-term outcome. OBJECTIVES: To investigate the relationships between early
      sedation and time to extubation, delirium, and hospital and 180-day mortality
      among ventilated critically ill patients in the intensive care unit (ICU).
      METHODS: Multicenter (25 Australia and New Zealand hospitals) prospective
      longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients
      ventilated and sedated 24 hours or more. We assessed administration of sedative
      agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale
      (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We
      used multivariable Cox regression to quantify relationships between early deep
      sedation (RASS, -3 to -5) and patients' outcomes. MEASUREMENTS AND MAIN RESULTS:
      We studied 251 patients (mean age, 61.7 +/- 15.9 yr; mean Acute Physiology and
      Chronic Health Evaluation [APACHE] II score, 20.8 +/- 7.8), with 21.1% (53)
      hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed
      14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4
      hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium
      occurred in 111 (50.7%) patients with median (interquartile range) duration of 2
      (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative,
      elective, hospital type, early use of vasopressors, and dialysis, early deep
      sedation was an independent predictor of time to extubation (hazard ratio [HR],
      0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR,
      1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01
      1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19).
      CONCLUSIONS: Early sedation depth independently predicts delayed extubation and
      increased mortality, making it a potential target for interventional studies.

PMID- 22859530
TI  - Reversible splenial lesion syndrome in pediatric systemic lupus erythematosus.

PMID- 22859531
TI  - Magnetic resonance angiography in psoriatic arthritis of the hand.

PMID- 22859533
TI  - Association of interleukin 1alpha promoter polymorphism (-889C/T) with
      susceptibility to systemic sclerosis.

PMID- 22859534
TI  - ANKH and renal stone formation in ankylosing spondylitis.

PMID- 22859535
TI  - A difficult case of polymyalgia rheumatica.

PMID- 22859536
TI  - Beneficial cardiovascular effects of low-dose glucocorticoid therapy in
      inflammatory rheumatic diseases.

PMID- 22859537
TI  - Myocardial positron emission tomography/computed tomography scan revealing right
      coronary artery involvement in large vessel vasculitis.

PMID- 22859538
TI  - Subcutaneous methotrexate to cut costs?

PMID- 22859539
TI  - A single-nucleotide polymorphism of CCR6 (rs3093024) is associated with
      susceptibility to rheumatoid arthritis but not ankylosing spondylitis, in a
      Taiwanese population.

PMID- 22859540
TI  - Recombinant human soluble thrombomodulin for treatment of thrombotic
      microangiopathy associated with lupus nephritis.

PMID- 22859541
TI  - An anatomic basis for volumetric evaluation of the neck.
AB  - BACKGROUND: A better understanding of volume distribution between the superficial
      (subcutaneous) and deep (subplatysmal) planes of the neck may be useful when
      deciding on the best course of management for patients presenting for cervical
      contouring. OBJECTIVES: The authors investigate the normal distribution of fat in
      the superficial and deep planes of the neck in a cadaver model, to determine the
      proportion of the submandibular gland that contributes to submental fullness.
      METHODS: Fat in the superficial and deep neck planes of 29 adult cadavers was
      dissected and weighed. The submandibular glands were also dissected and the
      cervical portion of each gland was shaved off, weighed, and compared to the
      weight of the whole gland. RESULTS: The mean weight of superficial fat collected
      from the specimens was 15.0 g in males (n = 14; range, 2.2-35.7 g) and 14.3 g in
      females (n = 15; range, 1.6-37.3 g); the mean weight of subplatysmal fat was 5.5
      g in males (range, 1.3-15.2 g) and 3.7 g in females (range, 0.6-15.1 g). Mean
      weight was not statistically significantly different between the sexes, nor
      between the 2 racial/ethnic groups (Caucasian, n = 14; Southeast Asian, n = 15).
      Approximately 40% of the submandibular gland was found to lie inferior to the
      lower border of the mandible in the specimens examined. The authors found no
      anatomical evidence of submandibular gland ptosis, even in the oldest specimens.
      CONCLUSIONS: The study provides a comprehensive analysis of the distribution of
      adipose tissue in the superficial and deep planes of the neck, as well as the
      contribution of the submandibular glands to submental volume. This objective
      evaluation of neck volume may help guide clinicians in the surgical planning
      process and provide a foundation for designing new cervicofacial rejuvenation
      techniques.

PMID- 22859542
TI  - The transconjunctival deep-plane midface lift: a 9-year experience working under
      the muscle.
AB  - BACKGROUND: Rejuvenation of the midface with a natural-looking, safe, and long
      lasting result is a challenge in aesthetic surgery. The ideal approach should be
      easy to perform, with minimal risk and significant benefit. The combination of
      transconjunctival exposure and preservation of the periosteum may result in lower
      morbidity than traditional midface rejuvenation. OBJECTIVES: The authors present
      their 9-year experience with the transconjunctival deep-plane midface lift (TDML)
      and discuss the benefits and limitations of this procedure relative to
      traditional approaches. METHODS: A retrospective review (2000-2009) was conducted
      of 124 consecutive patients treated by the same surgeon (JWF) with the TDML
      approach. The technique combines transconjunctival and preperiosteal dissection
      under direct vision. Collected data included patient demographics, operative
      technique, concomitant procedures, and postoperative results. Complications and
      revisions were reviewed to assess safety and long-term efficacy. RESULTS:
      Patients included 97 women and 27 men, with a minimum of 13 months of
      postoperative follow-up (median, 56 months). The mean operating time for upper
      blepharoplasty with TDML was less than 150 minutes. No significant complications
      occurred. One patient required reexcision of redundant lower eyelid skin, and
      another patient underwent secondary excision via traditional midface lift.
      CONCLUSIONS: The TDML procedure is safe and effective. The technique is readily
      applicable and more "forgiving" than the traditional midface lift. With proper
      patient selection, the limited soft-tissue dissection reduces surgical morbidity.
      Patients with excessive skin redundancy or festoons should be treated with more
      traditional techniques.

PMID- 22859543
TI  - Vertical reduction mammaplasty utilizing the superomedial pedicle: is it really
      for everyone?
AB  - BACKGROUND: Classically, the vertical-style reduction mammaplasty utilizing a
      superomedial pedicle has been limited to smaller reductions secondary to concerns
      for poor wound healing and nipple necrosis. OBJECTIVES: The authors reviewed a
      large cohort of patients who underwent a vertical-style superomedial pedicle
      reduction mammaplasty in an attempt to demonstrate its safety and efficacy in
      treating symptomatic macromastia. METHODS: A retrospective review was performed
      of 290 patients (558 breasts) who underwent a vertical-style superomedial pedicle
      reduction mammaplasty. All procedures were conducted by one of 4 plastic surgeons
      over 6 years (JDR, MAA, DLV, DRA). RESULTS: The average resection weight was
      551.7 g (range, 176-1827 g), with 4.6% of resections greater than 1000 g. A
      majority of patients (55.2%) concomitantly underwent liposuction of the breast.
      The total complication rate was 22.7%, with superficial dehiscence (8.8%) and
      hypertrophic scarring (8.8%) comprising the majority. Nipple sensory changes
      occurred in 1.6% of breasts, with no episodes of nipple necrosis. The revision
      rate was 2.2%. Patients with complications had significantly higher resection
      volumes and nipple-to-fold distances (P = .014 and .010, respectively).
      CONCLUSIONS: The vertical-style superomedial pedicle reduction mammaplasty is
      safe and effective for a wide range of symptomatic macromastia. The nipple-areola
      complex can be safely transposed, even in patients with larger degrees of
      macromastia, with no episodes of nipple necrosis. The adjunctive use of
      liposuction should be considered safe. Last, revision rates were low, correlating
      with a high level of patient satisfaction.

PMID- 22859544
TI  - Commentary on: Vertical reduction mammaplasty utilizing the superomedial pedicle:
      is it really for everyone?

PMID- 22859545
TI  - Commentary on: Progressive tension sutures in abdominoplasty: a review of 597
      consecutive cases.

PMID- 22859546
TI  - Application of fluorescent in situ hybridization in the mouse xenograft model of
      human fat grafting.
AB  - BACKGROUND: Determining the optimal technique for autologous fat grafting
      requires elucidation of the engraftment process at the cellular level. The nude
      mouse xenograft model for autologous human fat grafting is an excellent tool to
      evaluate the incorporation of grafted fat into the recipient. OBJECTIVES: The
      authors present a murine xenograft model that uses fluorescent in situ
      hybridization (FISH) to differentiate between murine (host) cells and human
      (grafted) cells. METHODS: Fat grafts were harvested from human abdominoplasty
      specimens, fixed, embedded in paraffin blocks, and cut into 5 um sections. The
      sections were stained and used for in situ hybridization with fluorescently
      labeled murine and human nucleic acid reagents. A fluorescence microscope was
      used for photographic analysis of the grafts, allowing identification of murine
      and human cell populations based on the wavelength at which they stained. DAPI
      (4,'6-diamidino-2-phenylindole) counterstaining was also applied to confirm that
      the images obtained represented cell nuclei. RESULTS: At 20* magnification,
      strong species-specific staining of cells was seen within the tissue sections,
      which allowed the authors to easily discriminate between graft-derived and host
      derived cells. Using this approach, human fat xenografts were revealed to
      comprise a complex matrix of closely interacting graft- and host-derived
      structures. CONCLUSIONS: FISH has the potential to be a powerful technique for
      distinguishing between murine and human cells in the nude mouse xenograft model
      of human fat grafting. By applying this technique, it may be possible to evaluate
      the engraftment process at a cellular level, which may ultimately allow
      clinicians to obtain more predictable results with grafted fat.

PMID- 22859547
TI  - What do patients want? Technical quality versus functional quality: a literature
      review for plastic surgeons.
AB  - While most surgeons are well aware of outcomes studies and quality assessment
      based on technical quality (TQ) measurements, there has been little attention
      given in the plastic surgery literature to the discussion of functional quality
      (FQ)-the process by which a health care service is delivered, as opposed to the
      actual procedure itself. Most patients judge the quality of their hospital
      experience based on FQ issues. They use their assessment of FQ to secondarily
      infer a judgment of the TQ level of a surgeon or facility. Surgeons, conversely,
      typically rate their own success with purely technical quality measures, paying
      little attention to FQ. This article reviews the relevant service-quality medical
      literature and introduces plastic surgeons to the importance of differentiating
      between TQ and FQ. Important FQ assessment techniques are reviewed. Implications
      for the plastic surgeon are discussed.

PMID- 22859548
TI  - Commentary on: What do patients want? Technical quality versus functional
      quality: a literature review for plastic surgeons.

PMID- 22859549
TI  - Commentary on: What do patients want? Technical quality versus functional
      quality: a literature review for plastic surgeons.

PMID- 22859550
TI  - Fat is exciting, but . . .

PMID- 22859551
TI  - Herpes virus outbreaks after dermal hyaluronic acid filler injections.

PMID- 22859552
TI  - The role of sponsored supplements in a peer-reviewed journal: a reply to an
      editorial.

PMID- 22859555
TI  - Relationship of physical and functional independence and perceived quality of
      life of veteran patients with Alzheimer disease.
AB  - Alzheimer disease not only affects the cognitive function but also impacts one's
      abilities to perform daily tasks. This study evaluated for correlation between
      the quality of life of patients with Alzheimer disease (QoL-AD) and the level of
      independence and to evaluate the statistical difference between patients' quality
      of life and proxy perception of quality of life by utilizing the Katz activities
      of daily living and QoL-AD on patients and QoL-AD on caregivers. There was a
      small positive correlation (r = .13) between the levels of physical and
      functional independence and the perceived QoL. Also, patient consistently had
      higher QoL-AD than their caregiver counterparts. These findings provide some
      insight into our need to acknowledge factors that may influence QoL and
      illustrate the importance of monitoring for executive dysfunction and the safety
      risk. 

PMID- 22859556
TI  - Evolution of trees and mycorrhizal fungi intensifies silicate mineral weathering.
AB  - Forested ecosystems diversified more than 350 Ma to become major engines of
      continental silicate weathering, regulating the Earth's atmospheric carbon
      dioxide concentration by driving calcium export into ocean carbonates. Our field
      experiments with mature trees demonstrate intensification of this weathering
      engine as tree lineages diversified in concert with their symbiotic mycorrhizal
      fungi. Preferential hyphal colonization of the calcium silicate-bearing rock,
      basalt, progressively increased with advancement from arbuscular mycorrhizal (AM)
      to later, independently evolved ectomycorrhizal (EM) fungi, and from gymnosperm
      to angiosperm hosts with both fungal groups. This led to 'trenching' of silicate
      mineral surfaces by AM and EM fungi, with EM gymnosperms and angiosperms
      releasing calcium from basalt at twice the rate of AM gymnosperms. Our findings
      indicate mycorrhiza-driven weathering may have originated hundreds of millions of
      years earlier than previously recognized and subsequently intensified with the
      evolution of trees and mycorrhizas to affect the Earth's long-term CO(2) and
      climate history.

PMID- 22859557
TI  - Environmental variability and acoustic signals: a multi-level approach in
      songbirds.
AB  - Among songbirds, growing evidence suggests that acoustic adaptation of song
      traits occurs in response to habitat features. Despite extensive study, most
      research supporting acoustic adaptation has only considered acoustic traits
      averaged for species or populations, overlooking intraindividual variation of
      song traits, which may facilitate effective communication in heterogeneous and
      variable environments. Fewer studies have explicitly incorporated sexual
      selection, which, if strong, may favour variation across environments. Here, we
      evaluate the prevalence of acoustic adaptation among 44 species of songbirds by
      determining how environmental variability and sexual selection intensity are
      associated with song variability (intraindividual and intraspecific) and short
      term song complexity. We show that variability in precipitation can explain short
      term song complexity among taxonomically diverse songbirds, and that
      precipitation seasonality and the intensity of sexual selection are related to
      intraindividual song variation. Our results link song complexity to environmental
      variability, something previously found for mockingbirds (Family Mimidae).
      Perhaps more importantly, our results illustrate that individual variation in
      song traits may be shaped by both environmental variability and strength of
      sexual selection.

PMID- 22859558
TI  - Proximity data-loggers increase the quantity and quality of social network data.
AB  - Social network analysis is an ideal quantitative tool for advancing our
      understanding of complex social behaviour. However, this approach is often
      limited by the challenges of accurately characterizing social structure and
      measuring network heterogeneity. Technological advances have facilitated the
      study of social networks, but to date, all such work has focused on large
      vertebrates. Here, we provide proof of concept for using proximity data-logging
      to quantify the frequency of social interactions, construct weighted networks and
      characterize variation in the social behaviour of a lek-breeding bird, the wire
      tailed manakin, Pipra filicauda. Our results highlight how this approach can
      ameliorate the challenges of social network data collection and analysis by
      concurrently improving data quality and quantity.

PMID- 22859559
TI  - Fire creates host plant patches for monarch butterflies.
AB  - Monarch butterflies (Danaus plexippus) depend on the presence of host plants
      (Asclepias spp.) within their breeding range for reproduction. In the southern
      Great Plains, Asclepias viridis is a perennial that flowers in May and June, and
      starts to senesce by August. It is locally abundant and readily used by monarchs
      as a host plant. We evaluated the effects of summer prescribed fire on A. viridis
      and the use of A. viridis by monarch butterflies. Summer prescribed fire
      generated a newly emergent population of A. viridis that was absent in other
      areas. Pre-migrant monarch butterflies laid eggs on A. viridis in summer burned
      plots in late August and September, allowing adequate time for a new generation
      of adult monarchs to emerge and migrate south to their overwintering grounds.
      Thus, summer prescribed fire may provide host plant patches and/or corridors for
      pre-migrant monarchs during a time when host plant availability may be limited in
      other areas.

PMID- 22859560
TI  - Conservation physiology of marine fishes: advancing the predictive capacity of
      models.
AB  - At the end of May, 17 scientists involved in an EU COST Action on Conservation
      Physiology of Marine Fishes met in Oristano, Sardinia, to discuss how physiology
      can be better used in modelling tools to aid in management of marine ecosystems.
      Current modelling approaches incorporate physiology to different extents, ranging
      from no explicit consideration to detailed physiological mechanisms, and across
      scales from a single fish to global fishery resources. Biologists from different
      sub-disciplines are collaborating to rise to the challenge of projecting future
      changes in distribution and productivity, assessing risks for local populations,
      or predicting and mitigating the spread of invasive species.

PMID- 22859561
TI  - Pro-sociality without empathy.
AB  - Empathy, the capacity to recognize and share feelings experienced by another
      individual, is an important trait in humans, but is not the same as pro
      sociality, the tendency to behave so as to benefit another individual. Given the
      importance of understanding empathy's evolutionary emergence, it is unsurprising
      that many studies attempt to find evidence for it in other species. To address
      the question of what should constitute evidence for empathy, we offer a critical
      comparison of two recent studies of rescuing behaviour that report similar
      phenomena but are interpreted very differently by their authors. In one of the
      studies, rescue behaviour in rats was interpreted as providing evidence for
      empathy, whereas in the other, rescue behaviour in ants was interpreted without
      reference to sharing of emotions. Evidence for empathy requires showing that
      actor individuals possess a representation of the receiver's emotional state and
      are driven by the psychological goal of improving its wellbeing. Proving
      psychological goal-directedness by current standards involves goal-devaluation
      and causal sensitivity protocols, which, in our view, have not been implemented
      in available publications. Empathy has profound significance not only for
      cognitive and behavioural sciences but also for philosophy and ethics and, in our
      view, remains unproven outside humans.

PMID- 22859562
TI  - Social familiarity modulates personality trait in a cichlid fish.
AB  - Personality traits, such as exploration-avoidance, are expected to be adaptive in
      a given context (e.g. low-risk environment) but to be maladaptive in others (e.g.
      high-risk environment). Therefore, it is expected that personality traits are
      flexible and respond to environmental fluctuations, given that consistency across
      different contexts is maintained, so that the relative individual responses in
      relation to others remains the same (i.e. although the magnitude of the response
      varies the differences between high and low responders are kept). Here, we tested
      the response of male cichlid fish (Oreochromis mossambicus) to a novel object
      (NO) in three different social contexts: (i) social isolation, (ii) in the
      presence of an unfamiliar conspecific, and (iii) in the presence of a familiar
      conspecific. Males in the familiar treatment exhibited more exploratory behaviour
      and less neophobia than males in either the unfamiliar or the social isolation
      treatments. However, there were no overall correlations in individual behaviour
      across the three treatments, suggesting a lack of consistency in exploration
      avoidance as measured by the NO test in this species. Moreover, there were no
      differences in cortisol responsiveness to an acute stressor between the three
      treatments. Together, these results illustrate how behavioural traits usually
      taken as measures of personality may exhibit significant flexibility and lack the
      expected consistency across different social contexts.

PMID- 22859563
TI  - Clinical results of external beam radiotherapy alone with a concomitant boost
      program or with conventional fractionation for cervical cancer patients who did
      not receive intracavitary brachytherapy.
AB  - A combination of external beam radiotherapy (EBRT) and intracavitary
      brachytherapy (ICBT) is well established as the standard radical radiotherapy
      (RT) for cervical cancer. However, it is sometimes necessary to perform EBRT
      alone for patients where ICBT is not feasible. For these patients, we initiated
      EBRT alone with three-dimensional conformal radiotherapy (3DCRT). The purpose of
      this study is to evaluate the results of EBRT alone without ICBT for patients
      with cervical cancer. Sixteen patients were treated with EBRT alone between 2002
      and 2009. There were three stage IIB, six stage IIIB and seven patients with
      stage IVA disease. A total of 10 patients were treated with a median dose of 66
      Gy with a median overall treatment time (OTT) of 40 days delivered by a
      concomitant boost (CCB), and a median dose of 60 Gy with a median OTT of 47 days
      was administered for six patients by conventional fractionation (CF). The 3-year
      overall survival (OAS) and local control (LC) rates were 43.8% and 75.0%,
      respectively. The 3-year LC rate was 90.0% for the CCB group, 50.0% for the CF
      group (P = 0.0692); 100% for OTT <=42 days, 42.9% for OTT >=43 days (P = 0.0095).
      No severe acute and late adverse effects were encountered for any of the
      patients. These outcomes suggest that EBRT with a CCB program may be a promising
      radical treatment for cervical cancer that provides better LC with minimal
      complications, especially in cases where ICBT cannot be performed.

PMID- 22859565
TI  - The dosimetric impact of respiratory breast movement and daily setup error on
      tangential whole breast irradiation using conventional wedge, field-in-field and
      irregular surface compensator techniques.
AB  - To evaluate the dosimetric impact of respiratory breast motion and daily setup
      error on whole breast irradiation (WBI) using three irradiation techniques;
      conventional wedge (CW), field-in-field (FIF) and irregular surface compensator
      (ISC). WBI was planned for 16 breast cancer patients. The dose indices for
      evaluated clinical target volume (CTV(evl)), lung, and body were evaluated. For
      the anterior-posterior (AP) respiratory motion and setup error of a single
      fraction, the isocenter was moved according to a sine function, and the dose
      indices were averaged over one period. Furthermore, the dose indices were
      weighted according to setup error frequencies that have a normal distribution to
      model systematic and random setup error for the entire treatment course. In all
      irradiation techniques, AP movement has a significant impact on dose
      distribution. CTV(evl)D(95) (the minimum relative dose that covers 95 % volume)
      and V(95) (the relative volume receiving 95 % of the prescribed dose) were
      observed to significantly decrease from the original ISC plan when simulated for
      the entire treatment course. In contrast, the D(95), V(95) and dose homogeneity
      index did not significantly differ from those of the original plans for FIF and
      CW. With regard to lung dose, the effect of motion was very similar among all
      three techniques. The dosimetric impact of AP respiratory breast motion and setup
      error was largest for the ISC technique, and the second greatest effect was
      observed with the FIF technique. However, these variations are relatively small.

PMID- 22859564
TI  - A digital model individual template and CT-guided 125I seed implants for
      malignant tumors of the head and neck.
AB  - To enhance the accuracy of radioactive seed implants in the head and neck, a
      digital model individual template, containing information simultaneously on
      needle pathway and facial features, was designed to guide implantation with CT
      imaging. Thirty-one patients with recurrent and local advanced malignant tumors
      of head and neck after prior surgery and radiotherapy were involved in this
      study. Before (125)I implants, patients received CT scans based on 0.75mm
      thickness. And the brachytherapy treatment planning system (BTPS) software was
      used to make the implantation plan based on the CT images. Mimics software and
      Geomagic software were used to read the data containing CT images and
      implantation plan, and to design the individual template. Then the individual
      template containing the information of needle pathway and face features
      simultaneously was made through rapid prototyping (RP) technique. All patients
      received (125)I seeds interstitial implantation under the guide of the individual
      template and CT. The individual templates were positioned easily and accurately,
      and were stable. After implants, treatment quality evaluation was made by CT and
      TPS. The seeds and dosages distribution (D(90),V(100),V(150)) were well meet the
      treatment requirement. Clinical practice confirms that this approach can
      facilitate easier and more accurate implantation.

PMID- 22859566
TI  - Cytogenetic biodosimetry for Fukushima travelers after the nuclear power plant
      accident: no evidence of enhanced yield of dicentrics.
AB  - Individuals who traveled to contaminated areas after the Fukushima nuclear
      accident have concerns about the health effects. However, medical follow-up for
      any adverse health effects will be difficult without personal dose measurements.
      Cytogenetic biodosimetry is a reasonable method of assessing absorbed doses
      retrospectively. We analyzed dicentric chromosomes for 265 Fukushima travelers,
      mostly journalists and rescue workers, who had been dispatched to northeastern
      Japan during the nuclear emergency. As a control group, 37 healthy volunteers who
      had not visited Japan since the accident were enrolled. Yields of dicentrics and
      absorbed doses calculated from a dose-response calibration curve for travelers
      and the control group were compared. The cut-off level for dicentric chromosomes
      in the controls was 3.5 per 1000 cells. Of the 265 travelers, 31 had elevated
      numbers of dicentrics (High-Dics group) while 234 were below the cut-off (Normal
      Dics group). All but one of the individuals in the High-Dics group also reported
      a significantly higher number of medical exposures to radiation within the past
      three years compared with the Normal-Dics or control groups. The 225 travelers
      with no history of medical exposure showed no difference of dicentrics yield
      compared to the control group. Our data indicate that Fukushima travel alone did
      not enhance the yield of dicentrics.

PMID- 22859567
TI  - Risk factors for rectal bleeding associated with I-125 brachytherapy for prostate
      cancer.
AB  - The purpose of this study was to determine the risk factors for rectal bleeding
      after prostate brachytherapy. Between April 2005 and September 2009, 89 patients
      with T1c-2cN0M0 prostate cancer were treated with permanent I-125 seed
      implantation alone. The prostate prescription dose was 145 Gy, and the grade of
      rectal bleeding was scored according to the Common Terminology Criteria for
      Adverse Events version 4.0. Post-treatment planning was performed with fusion
      images of computerized tomography and magnetic resonance imaging 4-5 weeks after
      brachytherapy. Patient characteristics and dosimetric parameters were evaluated
      to determine risk factors for bleeding. The calculated parameters included the
      rectal volume in cubic centimeters that received >50-200% of the prescribed dose
      (RV50-200) and the minimal doses received by 1-30% of the rectal volume (RD1-30).
      The median follow-up time was 42 months (ranging 18-73 months). Grade 1 rectal
      bleeding occurred in 24 (27.0%) patients, but no Grade 2 or severe bleeding was
      observed. Usage of anticoagulants had a significant correlation with the
      occurrence of bleeding (P = 0.007). The RV100-150 and RD1-10 were significantly
      higher in patients with rectal bleeding than in those without bleeding. The RV100
      was identified as a possible threshold value; the 3-year rectal bleeding rate in
      patients with an RV100 > 1.0 cm(3) was 36%, whereas that with an RV100 <= 1.0
      cm(3) was 14% (P < 0.05). Although no Grade 2 morbidity developed in this study,
      the RV100 should be kept below 1.0 cm(3), especially in additional dose-escalated
      brachytherapy.

PMID- 22859568
TI  - Physical basis for the adaptive flexibility of Bacillus spore coats.
AB  - Bacillus spores are highly resistant dormant cells formed in response to
      starvation. The spore is surrounded by a structurally complex protein shell, the
      coat, which protects the genetic material. In spite of its dormancy, once
      nutrient is available (or an appropriate physical stimulus is provided) the spore
      is able to resume metabolic activity and return to vegetative growth, a process
      requiring the coat to be shed. Spores dynamically expand and contract in response
      to humidity, demanding that the coat be flexible. Despite the coat's critical
      biological functions, essentially nothing is known about the design principles
      that allow the coat to be tough but also flexible and, when metabolic activity
      resumes, to be efficiently shed. Here, we investigated the hypothesis that these
      apparently incompatible characteristics derive from an adaptive mechanical
      response of the coat. We generated a mechanical model predicting the emergence
      and dynamics of the folding patterns uniformly seen in Bacillus spore coats.
      According to this model, spores carefully harness mechanical instabilities to
      fold into a wrinkled pattern during sporulation. Owing to the inherent
      nonlinearity in their formation, these wrinkles persist during dormancy and allow
      the spore to accommodate changes in volume without compromising structural and
      biochemical integrity. This characteristic of the spore and its coat may inspire
      design of adaptive materials.

PMID- 22859569
TI  - A dynamical model for the Utricularia trap.
AB  - We propose a model that captures the dynamics of a carnivorous plant, Utricularia
      inflata. This plant possesses tiny traps for capturing small aquatic animals.
      Glands pump water out of the trap, yielding a negative pressure difference
      between the plant and its surroundings. The trap door is set into a meta-stable
      state and opens quickly as an extra pressure is generated by the displacement of
      a potential prey. As the door opens, the pressure difference sucks the animal
      into the trap. We write an ODE model that captures all the physics at play. We
      show that the dynamics of the plant is quite similar to neuronal dynamics and we
      analyse the effect of a white noise on the dynamics of the trap.

PMID- 22859571
TI  - Killing and disabling: a comment on Sinnott-Armstrong and Miller.

PMID- 22859570
TI  - Diversity in the protein N-glycosylation pathways within the Campylobacter genus.
AB  - The foodborne bacterial pathogen, Campylobacter jejuni, possesses an N-linked
      protein glycosylation (pgl) pathway involved in adding conserved heptasaccharides
      to asparagine-containing motifs of >60 proteins, and releasing the same glycan
      into its periplasm as free oligosaccharides. In this study, comparative genomics
      of all 30 fully sequenced Campylobacter taxa revealed conserved pgl gene clusters
      in all but one species. Structural, phylogenetic and immunological studies showed
      that the N-glycosylation systems can be divided into two major groups. Group I
      includes all thermotolerant taxa, capable of growth at the higher body
      temperatures of birds, and produce the C. jejuni-like glycans. Within group I,
      the niche-adapted C. lari subgroup contain the smallest genomes among the
      epsilonproteobacteria, and are unable to glucosylate their pgl pathway glycans
      potentially reminiscent of the glucosyltransferase regression observed in the O
      glycosylation system of Neisseria species. The nonthermotolerant Campylobacters,
      which inhabit a variety of hosts and niches, comprise group II and produce an
      unexpected diversity of N-glycan structures varying in length and composition.
      This includes the human gut commensal, C. hominis, which produces at least four
      different N-glycan structures, akin to the surface carbohydrate diversity
      observed in the well-studied commensal, Bacteroides. Both group I and II glycans
      are immunogenic and cell surface exposed, making these structures attractive
      targets for vaccine design and diagnostics.

PMID- 22859572
TI  - Antipsychotics: is it time to introduce patient choice?
AB  - Evidence regarding overestimation of the efficacy of antipsychotics and
      underestimation of their toxicity, as well as emerging data regarding alternative
      treatment options, suggests it may be time to introduce patient choice and
      reconsider whether everyone who meets the criteria for a schizophrenia spectrum
      diagnosis requires antipsychotics in order to recover.

PMID- 22859573
TI  - Perspectives on the Incredible Years programme: psychological management of
      conduct disorder.
AB  - Two out of three children diagnosed with conduct disorder will not outgrow it
      without treatment. It is costly to the individual in terms of negative life
      outcomes and to society in terms of increased health, social and education
      service use. Psychosocial interventions are effective in psychologically managing
      and preventing the onset of conduct disorder.

PMID- 22859574
TI  - Autism spectrum disorder: prevalence and cause may be bound together.
AB  - Autism has been in the forefront of science and public concern because of
      reported increases in its prevalence. Changing diagnostic practice and improved
      identification explain some of this rise, but there may also be a true increase.
      Aetiological research needs to include environmental factors to understand the
      causes of autism.

PMID- 22859575
TI  - Adjustment disorder: implications for ICD-11 and DSM-5.
AB  - Adjustment disorder has been a recognised disorder for decades but has been the
      subject of little epidemiological research. Now researchers have identified the
      prevalence of adjustment disorder in primary care, and found general practitioner
      recognition very low but with high rates of antidepressant prescribing. Possible
      reasons for the seemingly low prevalence, recognition rate and inappropriate
      management include its recognition as a residual category in diagnostic
      instruments and poor delineation from other disorders or from normal stress
      responses. These problems could be rectified in ICD-11 and DSM-5 if changes
      according it full syndromal status, among others, were made. This would have an
      impact on future research.

PMID- 22859576
TI  - Clinical recognition and recording of alcohol disorders by clinicians in primary
      and secondary care: meta-analysis.
AB  - BACKGROUND: Clinicians have considerable difficulty identifying and helping those
      people with alcohol problems but no previous study has looked at this
      systematically. AIMS: To determine clinicians' ability to routinely identify
      broadly defined alcohol problems. METHOD: Data were extracted and rated by two
      authors, according to PRISMA standard and QUADAS criteria. Studies that examined
      the diagnostic accuracy of clinicians' opinion regarding the presence of alcohol
      problems as well as their written notation were evaluated. RESULTS: A
      comprehensive search identified 48 studies that looked at the routine ability of
      clinicians to identify alcohol problems (12 in primary care, 31 in general
      hospitals and 5 in psychiatric settings). A total of 39 examined alcohol use
      disorder, 5 alcohol dependence and 4 intoxication. We separated studies into
      those using self-report and those using interview. The diagnostic sensitivity of
      primary care physicians (general practitioners) in the identification of alcohol
      use disorder was 41.7% (95% CI 23.0-61.7) but alcohol problems were recorded
      correctly in only 27.3% (95% CI 16.9-39.1) of primary care records. Hospital
      staff identified 52.4% (95% CI 35.9-68.7) of cases and made correct notations in
      37.2% (95% CI 28.4-46.4) of case notes. Mental health professionals were able to
      correctly identify alcohol use disorder in 54.7% (95% CI 16.8-89.6) of cases.
      There were limited data regarding alcohol dependency and intoxication. Hospital
      staff were able to detect 41.7% (95% CI 16.5-69.5) of people with alcohol
      dependency and 89.8% (95% CI 70.4-99.4) of those acutely intoxicated. Specificity
      data were sparse. CONCLUSIONS: Clinicians may consider simple screening methods
      such as self-report tools rather than relying on unassisted clinical judgement
      but the added value of screening over and above clinical diagnosis remains
      unclear.

PMID- 22859577
TI  - Is the moon there when nobody looks?

PMID- 22859578
TI  - Suicide in Wales.

PMID- 22859580
TI  - Clinimetrics and psychometrics: never the twain shall meet?

PMID- 22859582
TI  - Chlamydia pneumoniae infection in adolescents with type 1 diabetes mellitus.
AB  - Chlamydia pneumoniae, an intracellular bacterium, is associated with respiratory
      diseases, reinfectivity and chronic diseases such as cardiovascular disease,
      hypertension and stroke. The risk of infection is higher and infections are a
      serious clinical problem in patients with type 1 (insulin-dependent) diabetes
      mellitus (T1DM). Although diabetes mellitus and hyperglycaemia are considered
      possible risk factors for various types of aetiological agents, the
      epidemiological evidence concerning C. pneumoniae infection is scanty. The aim of
      the present study was to evaluate the impact of glycosylated haemoglobin (HbA1c)
      levels, an indicator of a hyperglycaemic state, on C. pneumoniae infection and
      disease chronicity; in addition we compared the duration of diabetes with the
      occurrence of C. pneumoniae infection. C. pneumoniae blood real time PCR and
      serology (IgG, IgA and IgM) assays by an ELISA method were performed. C.
      pneumoniae DNA was detected in 46.5 % [95 % confidence interval (CI) = 35.1-57.9
      %] of the patients with T1DM; this prevalence is higher (P<0.05) than in non
      diabetic paediatric controls, 10.5 % (95 % CI = 3.6-17.4 %). IgG/IgA C.
      pneumoniae antibody positivity was significantly (P<=0.05) more common in
      patients in poor metabolic control (HbA1c >9 %) versus patients in good metabolic
      control (HbA1c <7 %), suggesting that the metabolic control of the disease is
      compromised in the patients with T1DM. In conclusion, adolescents with T1DM were
      more likely to show signs of infection with C. pneumoniae compared with healthy
      adolescents and the results suggest an increased risk of progressing from an
      acute C. pneumoniae infection to a chronic form.

PMID- 22859583
TI  - Temporal interferon-gamma release response to Mycobacterium kansasii infection in
      an anorexia nervosa patient.
AB  - Due to the differences in the management of Mycobacterium kansasii disease and
      tuberculosis, an accurate diagnosis is required. This report, which describes
      what we believe to be the first documented case of M. kansasii infection in a
      patient suffering from anorexia nervosa, sheds light on the possible occurrence
      of a non-tuberculous mycobacterial infection that can mimic tuberculosis, on the
      risk of a misleading interpretation of interferon-gamma release assays, and on
      the temporal response to these tests.

PMID- 22859584
TI  - A multiplex real-time PCR assay for the detection and differentiation of
      Francisella tularensis subspecies.
AB  - Francisella tularensis is the aetiological agent of tularaemia, a zoonotic
      disease with worldwide prevalence. F. tularensis is a highly pathogenic organism
      and has been designated a category A biothreat agent by the Centers for Disease
      Control and Prevention. Tularaemia is endemic in much of the USA, Europe and
      parts of Asia. It is transmitted by numerous vectors and vehicles such as deer
      flies, ticks and rabbits. Currently, there are four recognized subspecies of F.
      tularensis: tularensis (type A), holarctica (type B), mediasiatica and novicida.
      Within the type A classification there are two subclassifications, type A.I and
      A.II, each with a specific geographical distribution across the USA. F.
      tularensis subsp. holartica (type B) is found in both the USA and Europe. Because
      of virulence differences among subtypes, it is important that health departments,
      hospitals and other government agencies are able to quickly identify each
      subtype. The purpose of this study was to develop a multiplex real-time PCR assay
      for the identification and discrimination of type A.I, type A.II, type B and
      novicida subspecies of F. tularensis. The assay was validated using 119 isolates
      of F. tularensis, three of its nearest neighbours and 14 other bacterial
      pathogens. This assay proved to be ~98 % successful at identifying the known
      subspecies of F. tularensis and could prove to be a useful tool in the
      characterization of this important pathogen.

PMID- 22859585
TI  - Rapid molecular detection of extended-spectrum beta-lactamase gene variants with
      a novel ligation-mediated real-time PCR.
AB  - Extended-spectrum beta-lactamases (ESBLs) are emerging worldwide, making rapid
      and adequate ESBL detection crucial for infection control measures as well as for
      the choice of correct antimicrobial therapy. The aim of this study was to compare
      the performance of a novel rapid ligation-mediated real-time PCR (LM-PCR) with a
      combination disc test (CDT). In total, 172 prospective putative ESBL-positive
      Enterobacteriaceae isolates from clinical specimens based on VITEK2 results were
      included in this study and tested with the phenotypic CDT and the LM-PCR.
      Positive ESBL results were obtained in 100 and 95 isolates using CDT and LM-PCR,
      respectively. The sensitivity, specificity, negative predictive value and
      positive predictive value of the LM-PCR were 99.0, 92.2, 98.6 and 94.0 %,
      respectively, compared with the CDT. The LM-PCR technique provides an important
      reduction in turnaround time (~4.5 h versus overnight incubation using CDT) for
      ESBL confirmation. As a consequence, all ESBL results are available within the
      same day, making this assay an important tool for rapid and accurate ESBL
      detection.

PMID- 22859588
TI  - Evaluation of the innovance d-dimer assay for the diagnosis of disseminated
      intravascular coagulopathy in different clinical settings.
AB  - Disseminated intravascular coagulopathy (DIC) is a serious disease with fatal
      consequences. We prospectively analyzed Innovance d-dimer immunoturbidimetric
      assay in 68 patients diagnosed with DIC on the background of malignancy (22),
      severe infection (20), or multitrauma (26) at a single institution between
      January 2010 and January 2011. Median age was 61 years (range 20-89). All
      patients were assessed according to the International Society of Thrombosis and
      Haemostasis (ISTH) DIC score. Applying a threshold of Innovance d-dimer of 10
      mg/L fibrinogen equivalent unit (normal <0.5) was correlated with the highest
      sensitivity in malignancy (86%) and trauma/surgery (80%) compared to 54% in
      infection. The specificity remained high at 97% in infection, 81% in trauma and
      77% in malignancy with a negative predictive value of 97% in trauma and
      malignancy, and 88% in infection. Our data suggest that Innovance d-dimer is a
      useful and simple tool that enhances the ISTH DIC diagnostic criteria. Further
      studies to confirm these findings are warranted. 

PMID- 22859589
TI  - Plasmodium infection decreases fecundity and increases survival of mosquitoes.
AB  - Long-lived mosquitoes maximize the chances of Plasmodium transmission. Yet, in
      spite of decades of research, the effect of Plasmodium parasites on mosquito
      longevity remains highly controversial. On the one hand, many studies report
      shorter lifespans in infected mosquitoes. On the other hand, parallel (but
      separate) studies show that Plasmodium reduces fecundity and imply that this is
      an adaptive strategy of the parasite aimed at redirecting resources towards
      longevity. No study till date has, however, investigated fecundity and longevity
      in the same individuals to see whether this prediction holds. In this study, we
      follow for both fecundity and longevity in Plasmodium-infected and uninfected
      mosquitoes using a novel, albeit natural, experimental system. We also explore
      whether the genetic variations that arise through the evolution of insecticide
      resistance modulate the effect of Plasmodium on these two life-history traits. We
      show that (i) a reduction in fecundity in Plasmodium-infected mosquitoes is
      accompanied by an increase in longevity; (ii) this increase in longevity arises
      through a trade-off between reproduction and survival; and (iii) in insecticide
      resistant mosquitoes, the slope of this trade-off is steeper when the mosquito is
      infected by Plasmodium (cost of insecticide resistance).

PMID- 22859590
TI  - Reassortant influenza A viruses in wild duck populations: effects on viral
      shedding and persistence in water.
AB  - Wild ducks of the genus Anas represent the natural hosts for a large genetic
      diversity of influenza A viruses. In these hosts, co-infections with different
      virus genotypes are frequent and result in high rates of genetic reassortment.
      Recent genomic data have provided information regarding the pattern and frequency
      of these reassortant viruses in duck populations; however, potential consequences
      on viral shedding and maintenance in the environment have not been investigated.
      On the basis of full-genome sequencing, we identified five virus genotypes, in a
      wild duck population in northwestern Minnesota (USA), that naturally arose from
      genetic reassortments. We investigated the effects of influenza A virus genotype
      on the viral shedding pattern in Mallards (Anas platyrhynchos) and the duration
      of infectivity in water, under different temperature regimens. Overall, we found
      that variation in the viral genome composition of these isolates had limited
      effects on duration, extent and pattern of viral shedding, as well as on the
      reduction of infectivity in water over time. These results support that, in wild
      ducks, functionally equivalent gene segments could be maintained in virus
      populations with no fitness costs when genetic reassortments occur.

PMID- 22859591
TI  - Reconstructing past species assemblages reveals the changing patterns and drivers
      of extinction through time.
AB  - Predicting future species extinctions from patterns of past extinctions or
      current threat status relies on the assumption that the taxonomic and biological
      selectivity of extinction is consistent through time. If the driving forces of
      extinction change through time, this assumption may be unrealistic. Testing the
      consistency of extinction patterns between the past and the present has been
      difficult, because the phylogenetically explicit methods used to model present
      day extinction risk typically cannot be applied to the data from the fossil
      record. However, the detailed historical and fossil records of the New Zealand
      avifauna provide a unique opportunity to reconstruct a complete, large faunal
      assemblage for different periods in the past. Using the first complete phylogeny
      of all known native New Zealand bird species, both extant and extinct, we show
      how the taxonomic and phylogenetic selectivity of extinction, and biological
      correlates of extinction, change from the pre-human period through Polynesian and
      European occupation, to the present. These changes can be explained both by
      changes in primary threatening processes, and by the operation of extinction
      filter effects. The variable patterns of extinction through time may confound
      attempts to identify risk factors that apply across time periods, and to infer
      future species declines from past extinction patterns and current threat status.

PMID- 22859592
TI  - Vertically transmitted viral endosymbionts of insects: do sigma viruses walk
      alone?
AB  - Insects are host to a wide range of vertically transmitted bacterial
      endosymbionts, but we know relatively little about their viral counterparts.
      Here, we discuss the vertically transmitted viral endosymbionts of insects,
      firstly examining the diversity of this group, and then focusing on the well
      studied sigma viruses that infect dipterans. Despite limited sampling, evidence
      suggests that vertically transmitted viruses may be common in insects. Unlike
      bacteria, viruses can be transmitted through sperm and eggs, a trait that allows
      them to rapidly spread through host populations even when infection is costly to
      the host. Work on Drosophila melanogaster has shown that sigma viruses and their
      hosts are engaged in a coevolutionary arms race, in which the spread of
      resistance genes in the host population is followed by the spread of viral
      genotypes that can overcome host resistance. In the long-term, associations
      between sigma viruses and their hosts are unstable, and the viruses persist by
      occasionally switching to new host species. It therefore seems likely that viral
      endosymbionts have major impacts on the evolution and ecology of insects.

PMID- 22859593
TI  - Social bonds affect anti-predator behaviour in a tolerant species of macaque,
      Macaca nigra.
AB  - Enduring positive social bonds between individuals are crucial for humans' health
      and well being. Similar bonds can be found in a wide range of taxa, revealing the
      evolutionary origins of humans' social bonds. Evidence suggests that these strong
      social bonds can function to buffer the negative effects of living in groups, but
      it is not known whether they also function to minimize predation risk. Here, we
      show that crested macaques (Macaca nigra) react more strongly to playbacks of
      recruitment alarm calls (i.e. calls signalling the presence of a predator and
      eliciting cooperative mobbing behaviour) if they were produced by an individual
      with whom they share a strong social bond. Dominance relationships between caller
      and listener had no effect on the reaction of the listener. Thus, strong social
      bonds may improve the coordination and efficiency of cooperative defence against
      predators, and therefore increase chances of survival. This result broadens our
      understanding of the evolution and function of social bonds by highlighting their
      importance in the anti-predator context.

PMID- 22859594
TI  - High morphological variation of vestibular system accompanies slow and infrequent
      locomotion in three-toed sloths.
AB  - The semicircular canals (SCs), part of the vestibular apparatus of the inner ear,
      are directly involved in the detection of angular motion of the head for
      maintaining balance, and exhibit adaptive patterns for locomotor behaviour.
      Consequently, they are generally believed to show low levels of intraspecific
      morphological variation, but few studies have investigated this assumption. On
      the basis of high-resolution computed tomography, we present here, to our
      knowledge, the first comprehensive study of the pattern of variation of the inner
      ear with a focus on Xenarthra. Our study demonstrates that extant three-toed
      sloths show a high level of morphological variation of the bony labyrinth of the
      inner ear. Especially, the variation in shape, relative size and angles of their
      SCs greatly differ from those of other, faster-moving taxa within Xenarthra and
      Placentalia in general. The unique pattern of variation in three-toed sloths
      suggests that a release of selection and/or constraints on their organ of balance
      is associated with the observed wide range of phenotypes. This release is
      coincident with their slow and infrequent locomotion and may be related, among
      other possible factors, to a reduced functional demand for a precise sensitivity
      to movement.

PMID- 22859595
TI  - Functional and evolutionary trade-offs co-occur between two consolidated memory
      phases in Drosophila melanogaster.
AB  - Memory is a complex and dynamic process that is composed of different phases. Its
      evolution under natural selection probably depends on a balance between fitness
      benefits and costs. In Drosophila, two separate forms of consolidated memory
      phases can be generated experimentally: anaesthesia-resistant memory (ARM) and
      long-term memory (LTM). In recent years, several studies have focused on the
      differences between these long-lasting memory types and have found that, at the
      functional level, ARM and LTM are antagonistic. How this functional relationship
      will affect their evolutionary dynamics remains unknown. We selected for flies
      with either improved ARM or improved LTM over several generations, and found that
      flies selected specifically for improvement of one consolidated memory phase show
      reduced performance in the other memory phase. We also found that improved LTM
      was linked to decreased longevity in male flies but not in females. Conversely,
      males with improved ARM had increased longevity. We found no correlation between
      either improved ARM or LTM and other phenotypic traits. This is, to our
      knowledge, the first evidence of a symmetrical evolutionary trade-off between two
      memory phases for the same learning task. Such trade-offs may have an important
      impact on the evolution of cognitive capacities. On a neural level, these results
      support the hypothesis that mechanisms underlying these forms of consolidated
      memory are, to some degree, antagonistic.

PMID- 22859596
TI  - Plant-ants use symbiotic fungi as a food source: new insight into the nutritional
      ecology of ant-plant interactions.
AB  - Usually studied as pairwise interactions, mutualisms often involve networks of
      interacting species. Numerous tropical arboreal ants are specialist inhabitants
      of myrmecophytes (plants bearing domatia, i.e. hollow structures specialized to
      host ants) and are thought to rely almost exclusively on resources derived from
      the host plant. Recent studies, following up on century-old reports, have shown
      that fungi of the ascomycete order Chaetothyriales live in symbiosis with plant
      ants within domatia. We tested the hypothesis that ants use domatia-inhabiting
      fungi as food in three ant-plant symbioses: Petalomyrmex phylax/Leonardoxa
      africana, Tetraponera aethiops/Barteria fistulosa and Pseudomyrmex
      penetrator/Tachigali sp. Labelling domatia fungal patches in the field with
      either a fluorescent dye or (15)N showed that larvae ingested domatia fungi.
      Furthermore, when the natural fungal patch was replaced with a piece of a (15)N
      labelled pure culture of either of two Chaetothyriales strains isolated from T.
      aethiops colonies, these fungi were also consumed. These two fungi often co-occur
      in the same ant colony. Interestingly, T. aethiops workers and larvae ingested
      preferentially one of the two strains. Our results add a new piece in the puzzle
      of the nutritional ecology of plant-ants.

PMID- 22859597
TI  - Mothers adjust offspring sex to match the quality of the rearing environment.
AB  - Theory predicts that mothers should adjust offspring sex ratios when the expected
      fitness gains or rearing costs differ between sons and daughters. Recent
      empirical work has linked biased offspring sex ratios to environmental quality
      via changes in relative maternal condition. It is unclear, however, whether
      females can manipulate offspring sex ratios in response to environmental quality
      alone (i.e. independent of maternal condition). We used a balanced within-female
      experimental design (i.e. females bred on both low- and high-quality diets) to
      show that female parrot finches (Erythrura trichroa) manipulate primary offspring
      sex ratios to the quality of the rearing environment, and not to their own body
      condition and health. Individual females produced an unbiased sex ratio on high
      quality diets, but over-produced sons in poor dietary conditions, even though
      they maintained similar condition between diet treatments. Despite the lack of
      sexual size dimorphism, such sex ratio adjustment is in line with predictions
      from sex allocation theory because nutritionally stressed foster sons were
      healthier, grew faster and were more likely to survive than daughters. These
      findings suggest that mothers may adaptively adjust offspring sex ratios to
      optimally match their offspring to the expected quality of the rearing
      environment.

PMID- 22859598
TI  - Thermal acclimation of interactions: differential responses to temperature change
      alter predator-prey relationship.
AB  - Different species respond differently to environmental change so that species
      interactions cannot be predicted from single-species performance curves. We
      tested the hypothesis that interspecific difference in the capacity for thermal
      acclimation modulates predator-prey interactions. Acclimation of locomotor
      performance in a predator (Australian bass, Macquaria novemaculeata) was
      qualitatively different to that of its prey (eastern mosquitofish, Gambusia
      holbrooki). Warm (25 degrees C) acclimated bass made more attacks than cold (15
      degrees C) acclimated fish regardless of acute test temperatures (10-30 degrees
      C), and greater frequency of attacks was associated with increased prey capture
      success. However, the number of attacks declined at the highest test temperature
      (30 degrees C). Interestingly, escape speeds of mosquitofish during predation
      trials were greater than burst speeds measured in a swimming arena, whereas
      attack speeds of bass were lower than burst speeds. As a result, escape speeds of
      mosquitofish were greater at warm temperatures (25 degrees C and 30 degrees C)
      than attack speeds of bass. The decline in the number of attacks and the increase
      in escape speed of prey means that predation pressure decreases at high
      temperatures. We show that differential thermal responses affect species
      interactions even at temperatures that are within thermal tolerance ranges. This
      thermal sensitivity of predator-prey interactions can be a mechanism by which
      global warming affects ecological communities.

PMID- 22859604
TI  - Activated Gs signaling in osteoblastic cells alters the hematopoietic stem cell
      niche in mice.
AB  - Adult hematopoiesis occurs primarily in the BM space where hematopoietic cells
      interact with stromal niche cells. Despite this close association, little is
      known about the specific roles of osteoblastic lineage cells (OBCs) in
      maintaining hematopoietic stem cells (HSCs), and how conditions affecting bone
      formation influence HSC function. Here we use a transgenic mouse model with the
      ColI(2.3) promoter driving a ligand-independent, constitutively active 5HT4
      serotonin receptor (Rs1) to address how the massive increase in trabecular bone
      formation resulting from increased G(s) signaling in OBCs impacts HSC function
      and blood production. Rs1 mice display fibrous dysplasia, BM aplasia, progressive
      loss of HSC numbers, and impaired megakaryocyte/erythrocyte development with
      defective recovery after hematopoietic injury. These hematopoietic defects
      develop without compensatory extramedullary hematopoiesis, and the loss of HSCs
      occurs despite a paradoxical expansion of stromal niche cells with putative HSC
      supportive activity (ie, endothelial, mesenchymal, and osteoblastic cells).
      However, Rs1-expressing OBCs show decreased expression of key HSC-supportive
      factors and impaired ability to maintain HSCs. Our findings indicate that long
      term activation of G(s) signaling in OBCs leads to contextual changes in the BM
      niche that adversely affect HSC maintenance and blood homeostasis.

PMID- 22859605
TI  - Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell
      lymphoma after chemotherapy.
AB  - The finding that many chemotherapeutic agents have immunostimulatory effects has
      provided the impetus to combine chemotherapy and immunotherapy for synergistic
      antitumor effects. However, the critical determinants of effective antitumor
      immunity after chemotherapy have not been defined. Here we report that adoptive
      transfer of tumor-specific CD4+ T cells after chemotherapy with cyclophosphamide
      gave rise to polyfunctional CD4+ effector cells, which in turn intensified the
      inflammatory milieu and enhanced the activation of CD8+ T cells in the tumor
      microenvironment. Although this combined chemoimmunotherapy initially resulted in
      progressive regression of advanced B-cell lymphoma, its therapeutic efficacy was
      not durable and most mice succumbed to late relapse. Notably, relapse was
      associated with acquisition of a tolerized phenotype in tumor-specific CD4+ T
      cells, characterized by overexpression of program death-1 (PD-1). Remarkably,
      effective antitumor immunity was maintained and cure became prevalent when
      polyfunctional CD4+ effector cells were prevented from undergoing PD-1-mediated
      tolerization, either by antibody blockade of the PD-1-PD-L1 pathway, or targeted
      ablation of PD-1 in tumor-specific CD4+ T cells. Our study suggests that tumor
      reactive CD4+ T cells act as the "gatekeepers" of the host antitumor immunity in
      the postchemotherapy setting, thereby their functional status governs the choice
      between eradication versus regrowth of residual tumors.

PMID- 22859606
TI  - Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of
      allogeneic HCT.
AB  - The outcome of allogeneic hematopoietic cell transplantation is influenced by
      donor/recipient genetic disparity at loci both inside and outside the MHC on
      chromosome 6p. Although disparity at loci within the MHC is the most important
      risk factor for the development of severe GVHD, disparity at loci outside the MHC
      that encode minor histocompatibility (H) antigens can elicit GVHD and GVL
      activity in donor/recipient pairs who are otherwise genetically identical across
      the MHC. Minor H antigens are created by sequence and structural variations
      within the genome. The enormous variation that characterizes the human genome
      suggests that the total number of minor H loci is probably large and ensures that
      all donor/recipient pairs, despite selection for identity at the MHC, will be
      mismatched for many minor H antigens. In addition to mismatch at minor H loci,
      unrelated donor/recipient pairs exhibit genetic disparity at numerous loci within
      the MHC, particularly HLA-DP, despite selection for identity at HLA-A, -B, -C,
      and -DRB1. Disparity at HLA-DP exists in 80% of unrelated pairs and clearly
      influences the outcome of unrelated hematopoietic cell transplantation; the
      magnitude of this effect probably exceeds that associated with disparity at any
      locus outside the MHC.

PMID- 22859608
TI  - BRAFV600E mutant protein is expressed in cells of variable maturation in
      Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a clinically and histologically
      heterogeneous disorder. Its classification as either reactive inflammatory or
      neoplastic has been a matter of debate. However, the recent finding of frequent
      BRAFV600E mutations in LCH argues for the latter. The exact cell type that
      harbors the mutation and is responsible for proliferation remains to be
      identified. We here apply a BRAFV600E mutation-specific antibody to detect the
      BRAF mutant cells in lesions from 89 patients with LCH. We found BRAFV600E
      mutations in 34 of 89 (38%) lesions. In lesions with the BRAFV600E mutation, the
      majority of cells coexpressing S-100 and CD1a harbored mutant BRAFV600E protein.
      These cells also expressed CD14 and CD36, whereas various fractions exhibited
      CD207. On the other hand, CD80 and CD86 expression was also present on BRAFV600E
      positive cells. Thus, cells of variable maturation, exhibiting an
      immunohistochemical profile compatible either with myeloid cell or with
      dedifferentiated Langerhans cell antigens, carry the BRAFV600E mutation. In
      conclusion, we identify and characterize the neoplastic cells in LCH with
      BRAFV600E mutations by applying a mutation-specific marker and demonstrate
      feasibility for routine screening.

PMID- 22859607
TI  - STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders
      of NK cells and T-cell large granular lymphocyte leukemia.
AB  - Chronic lymphoproliferative disorders of natural killer cells (CLPD-NKs) and T
      cell large granular lymphocytic leukemias (T-LGLs) are clonal
      lymphoproliferations arising from either natural killer cells or cytotoxic T
      lymphocytes (CTLs). We have investigated for distribution and functional
      significance of mutations in 50 CLPD-NKs and 120 T-LGL patients by direct
      sequencing, allele-specific PCR, and microarray analysis. STAT3 gene mutations
      are present in both T and NK diseases: approximately one-third of patients with
      each type of disorder convey these mutations. Mutations were found in exons 21
      and 20, encoding the Src homology 2 domain. Patients with mutations are
      characterized by symptomatic disease (75%), history of multiple treatments, and a
      specific pattern of STAT3 activation and gene deregulation, including increased
      expression of genes activated by STAT3. Many of these features are also found in
      patients with wild-type STAT3, indicating that other mechanisms of STAT3
      activation can be operative in these chronic lymphoproliferative disorders.
      Treatment with STAT3 inhibitors, both in wild-type and mutant cases, resulted in
      accelerated apoptosis. STAT3 mutations are frequent in large granular lymphocytes
      suggesting a similar molecular dysregulation in malignant chronic expansions of
      NK and CTL origin. STAT3 mutations may distinguish truly malignant
      lymphoproliferations involving T and NK cells from reactive expansions.

PMID- 22859609
TI  - Safety and pharmacokinetics of a novel recombinant fusion protein linking
      coagulation factor IX with albumin (rIX-FP) in hemophilia B patients.
AB  - A recombinant fusion protein linking coagulation factor IX (FIX) with human
      albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less
      frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously
      treated subjects with hemophilia B (FIX <= 2 IU/dL) examined the safety and
      pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort
      underwent a comparative pharmacokinetics assessment with their previous FIX
      product (plasma-derived or recombinant). No allergic reactions or inhibitors were
      observed. Four mild, possibly treatment-related adverse events were reported. In
      the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours,
      more than 5 times longer than the subjects' previous FIX product. After 25 or 50
      IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained
      elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL
      and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than
      both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg,
      respectively). These results demonstrated both the safety and improved
      pharmacokinetics of rIX-FP, thus indicating this new product with extended half
      life as possibly able to control and prevent bleeding with less frequent
      injection.

PMID- 22859610
TI  - Reversible skeletal disease and high fluoride serum levels in hematologic
      patients receiving voriconazole.
AB  - We here investigate the occurrence of fluoride intake-associated alterations in
      patients with hematologic disease on triazol antifungal medication. Clinical,
      laboratory, and radiology data of overall 43 patients with hematologic
      malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole
      (n = 4), and a hematologic patient control group (n = 11) are described. Bone
      pain and radiologic evidence of periostitis were exclusively observed in patients
      receiving long-term voriconazole. Cessation of treatment led to clinical
      improvement in all cases. In line with clinical evidence, fluoride serum
      concentration was elevated in patients receiving voriconazole (median, 156.5
      MUg/L; interquartile range, 96.8 MUg/L; normal < 30 MUg/L) but not in the other
      treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that
      serum fluoride levels were elevated on average 5-fold above normal levels in
      hematologic patients receiving voriconazole. Clinically relevant skeletal disease
      was associated with renal insufficiency and above 10-fold elevated fluoride
      levels, and was reversible on termination of voriconazole treatment.

PMID- 22859611
TI  - Defective regulatory B-cell compartment in patients with immune thrombocytopenia.
AB  - B lymphocytes producing antiplatelet autoantibodies play a major role in
      autoimmune thrombocytopenia (ITP). However, certain B cells, including the human
      CD19(+)CD24(hi)CD38(hi) subpopulation, possess regulatory functions mediated
      partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who
      consisted of patients off treatment, we found a lower frequency of
      CD19(+)CD24(hi)CD38(hi) in the peripheral compartment of nonsplenectomized
      patients (P = .03). IL-10 expression after activation was decreased in all ITP
      circulating CD19(+) subpopulations (P < .03), and inhibition of monocyte TNF
      alpha expression by activated B cells was reduced in patients with platelet
      numbers of < 50 * 10(9) cells/L (P = .001), indicating that regulatory B cells of
      patients with ITP are functionally impaired in their ability to dampen monocyte
      activation. Interestingly, in nonsplenectomized patients whose platelet counts
      were elevated after treatment with thrombopoietic agents, the frequency of
      CD19(+)CD24(hi)CD38(hi) B cells was increased compared with those before
      treatment (P = .02). Altogether, these data indicate a compromised regulatory B
      cell compartment as an additional defect in immune regulation in patients with
      chronic ITP that may be restored in responders to thrombopoietic treatment.

PMID- 22859612
TI  - Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic
      vessels in mammalian embryos.
AB  - The lymphatic vasculature preserves tissue fluid balance by absorbing fluid and
      macromolecules and transporting them to the blood vessels for circulation. The
      stepwise process leading to the formation of the mammalian lymphatic vasculature
      starts by the expression of the gene Prox1 in a subpopulation of blood
      endothelial cells (BECs) on the cardinal vein (CV) at approximately E9.5. These
      Prox1-expressing lymphatic endothelial cells (LECs) will exit the CV to form
      lymph sacs, primitive structures from which the entire lymphatic network is
      derived. Until now, no conclusive information was available regarding the
      cellular processes by which these LEC progenitors exit the CV without
      compromising the vein's integrity. We determined that LECs leave the CV by an
      active budding mechanism. During this process, LEC progenitors are interconnected
      by VE-cadherin-expressing junctions. Surprisingly, we also found that Prox1
      expressing LEC progenitors were present not only in the CV but also in the
      intersomitic vessels (ISVs). Furthermore, as LEC progenitors bud from the CV and
      ISVs into the surrounding mesenchyme, they begin expressing the lymphatic marker
      podoplanin, migrate away from the CV, and form the lymph sacs. Analyzing this
      process in Prox1-null embryos revealed that Prox1 activity is necessary for LEC
      progenitors to exit the CV.

PMID- 22859614
TI  - All0809/8/7 is a DevBCA-like ABC-type efflux pump required for diazotrophic
      growth in Anabaena sp. PCC 7120.
AB  - Efflux pumps export a wide variety of proteinaceous and non-proteinaceous
      substrates across the Gram-negative cell wall. For the filamentous cyanobacterium
      Anabaena sp. strain PCC 7120, the ATP-driven glycolipid efflux pump DevBCA-TolC
      has been shown to be crucial for the differentiation of N(2)-fixing heterocysts
      from photosynthetically active vegetative cells. In this study, a homologous
      system was described. All0809/8/7-TolC form a typical ATP-driven efflux pump as
      shown by surface plasmon resonance. This putative exporter is also involved in
      diazotrophic growth of Anabaena sp. PCC 7120. A mutant in all0809 encoding the
      periplasmic membrane fusion protein of the pump was not able to grow without
      combined nitrogen. Although heterocysts of this mutant were not distinguishable
      from those of the wild-type in light and electron micrographs, they were impaired
      in providing the microoxic environment necessary for N(2) fixation. RT-PCR of
      all0809 transcripts and localization studies on All0807-GFP revealed that
      All0809/8/7 was initially downregulated during heterocyst maturation and
      upregulated at later stages of heterocyst formation in all cells of the filament.
      A substrate of the efflux pump could not be identified in ATP hydrolysis assays.
      We discuss a role for All0809/8/7-TolC in maintaining the continuous periplasm
      and how this would be of special importance for heterocyst differentiation.

PMID- 22859613
TI  - Haemin represses the haemolytic activity of Staphylococcus aureus in an Sae
      dependent manner.
AB  - Staphylococcus aureus is a major human pathogen and a common cause of nosocomial
      infections. This facultative pathogen produces a large arsenal of virulence
      factors, including the haemolysins, which allow the bacterium to lyse
      erythrocytes and thereby release large amounts of the haem-containing
      haemoglobin. The released haem is thought to be the main iron source of this
      organism during the course of infection, and is considered to be crucial for
      bacterial proliferation in vivo. High concentrations of haem and its degradation
      products, on the other hand, are known to be toxic for S. aureus, making it
      essential for the pathogen to tightly control haem release from red blood cells.
      Here we show that S. aureus responds to haemin by downregulating the expression
      of haemolysins. Subinhibitory concentrations of haemin were found to
      significantly reduce transcription of the haemolysin genes hlb (encoding beta
      haemolysin) and hlgA (encoding the S-class component of gamma-haemolysin), while
      hla (encoding alpha-haemolysin) and RNAIII (encoding delta-haemolysin)
      transcription did not appear to be affected. The presence of haemin also reduced
      the haemolytic potential of the supernatants of S. aureus LS1 cultures.
      Inactivation of the sae locus in LS1 abolished the haemin effect on the
      transcription of haemolysin genes, indicating that the two-component regulatory
      system is required for this regulatory effect. Iron limitation, on the other
      hand, was found to induce the expression of haemolysins, and this effect was
      again abolished in the sae mutant, indicating that S. aureus modulates its
      haemolysin production in response to iron and haem availability in an Sae
      dependent manner.

PMID- 22859616
TI  - PhpA, a tyrosine phosphatase of Myxococcus xanthus, is involved in the production
      of exopolysaccharide.
AB  - Protein-tyrosine phosphorylation plays a significant role in multiple cellular
      functions in bacteria. Bacterial tyrosine phosphatases catalyse the
      dephosphorylation of tyrosyl-phosphorylated proteins. Myxococcus xanthus PhpA
      shares homology with DNA polymerase and histidinol phosphatase family members.
      Recombinant His-tagged PhpA requires Mn(2+) or Co(2+) for phosphatase activity,
      and shows strict specificity for phosphorylated tyrosine residues. The k(m)
      values of PhpA for p-nitrophenyl phosphate (pNPP) and phosphotyrosine peptide,
      RRLIEDAEpYAARG, were 803 and 139 uM, respectively. The phosphatase activity of
      PhpA was inhibited by sodium orthovanadate with a k(i) of 33 uM. phpA gene
      expression was observed under both vegetative and developmental conditions, but
      peaked during late fruiting body formation. A phpA mutant exhibited an elevated
      level of tyrosine phosphorylation of a 79 kDa protein and cytoplasmic tyrosine
      kinase, BtkA. In M. xanthus, exopolysaccharide (EPS) is essential for cell-cell
      adhesion and fruiting body formation. phpA mutant cells exhibited enhanced
      capacity for cell-cell agglutination in agglutination buffer. Under starvation
      conditions, phpA mutation caused early aggregation and sporulation. The EPS
      production assay showed that the phpA mutant produced an increased amount of EPS
      in comparison with the wild-type. These results indicate that PhpA may negatively
      regulate the production of EPS in M. xanthus.

PMID- 22859615
TI  - Antigen variability in Anaplasma phagocytophilum during chronic infection of a
      reservoir host.
AB  - Anaplasma phagocytophilum is an obligately intracellular, tick-transmitted,
      bacterial pathogen of humans and other animals. In order to evade host immunity
      during the course of infection, A. phagocytophilum utilizes gene conversion to
      shuffle approximately 100 functional pseudogenes into a single expression
      cassette of the msp2(p44) gene, which encodes the major surface antigen, major
      surface protein 2 (Msp2). The role and extent of msp2(p44) recombination in a
      reservoir host for A. phagocytophilum have not been evaluated. In the current
      study, we explored patterns of recombination and expression site variability of
      the msp2(p44) gene in three chronically infected woodrats, a reservoir for the
      disease in the Western USA. All three woodrats developed persistent infection of
      at least 6 months duration; two of them maintained active infection for at least
      8 months. In total, we detected the emergence of 60 unique msp2(p44) expression
      site variants with no common temporal patterns of expression site recombination
      among the three A. phagocytophilum populations. Both the strength of infection
      (i.e. pathogen load) and the genetic diversity of pseudogenes detected at the
      msp2(p44) expression site fluctuated periodically during the course of infection.
      An analysis of the genomic pseudogene exhaustion rate showed that the repertoire
      of pseudogenes available to the A. phagocytophilum population could in theory
      become depleted within a year. However, the apparent emergence of variant
      pseudogenes suggests that the pathogen could potentially evade host immunity
      indefinitely. Our findings suggest a tightly co-evolved relationship between A.
      phagocytophilum and woodrats in which the pathogen perpetually evades host
      immunity yet causes no detectable disease.

PMID- 22859617
TI  - The two-component system PrlS/PrlR of Brucella melitensis is required for
      persistence in mice and appears to respond to ionic strength.
AB  - Bacterial adaptation to environmental conditions is essential to ensure maximal
      fitness in the face of several stresses. In this context, two-component systems
      (TCSs) represent a predominant signal transduction mechanism, allowing an
      appropriate response to be mounted when a stimulus is sensed. As facultative
      intracellular pathogens, Brucella spp. face various environmental conditions, and
      an adequate response is required for a successful infection process. Recently,
      bioinformatic analysis of Brucella genomes predicted a set of 15 bona fide TCS
      pairs, among which some have been previously investigated. In this report, we
      characterized a new TCS locus called prlS/R, for probable proline sensor
      regulator. It encodes a hybrid histidine kinase (PrlS) with an unusual
      Na(+)/solute symporter N-terminal domain and a transcriptional regulator
      (belonging to the LuxR family) (PrlR). In vitro, Brucella spp. with a functional
      PrlR/S system form bacterial aggregates, which seems to be an adaptive response
      to a hypersaline environment, while a prlS/R mutant does not. We identified ionic
      strength as a possible signal sensed by this TCS. Finally, this work correlates
      the absence of a functional PrlR/S system with the lack of hypersaline-induced
      aggregation in particular marine Brucella spp.

PMID- 22859618
TI  - Effect of red wine consumption on biomarkers of oxidative stress.
AB  - AIMS: To evaluate the effect of acute and chronic consumption of red wine or de
      alcoholized red wine with a similar antioxidant capacity on plasma total
      antioxidant capacity (TEAC), nuclear factor-kappaB (NF-kappaB) activity and F2
      isoprostanes (8-iso-PGF(2alpha)) in healthy men. METHODS: Nineteen healthy men
      with an increased waist circumference (>=94 cm) and a body mass index above 25
      kg/m(2) participated in a randomized, controlled crossover design trial. They
      daily consumed 450 ml of red wine (four drinks; 41.4 g alcohol) or 450 ml of de
      alcoholized red wine during dinner for 4 weeks each. On the last day of each
      treatment period, blood was collected before and 1 h after a standardized dinner
      with red wine or de-alcoholized red wine and also 24-h urine was collected.
      RESULTS: Absolute TEAC levels were higher 1 h after dinner with red wine compared
      with dinner with de-alcoholized red wine (1.3 versus 1.1 mmol Trolox
      equivalents/l; P = 0.03). Consumption of dinner together with de-alcoholized red
      wine acutely stimulated NF-kappaB activity in peripheral blood mononuclear cells
      (0.4-0.7 HeLa equivalents/2.5 MUg protein; P = 0.006), whereas this increase was
      completely suppressed when the dinner was combined with red wine. A chronic
      increase in urinary 8-iso-PGF(2alpha) after 4 weeks of red wine consumption
      compared with de-alcoholized red wine consumption (157 pg/mg creatinine and 141
      pg/mg creatinine, respectively, P = 0.006) was also observed. CONCLUSIONS:
      Consumption of a moderate dose of red wine can acutely increase plasma TEAC and
      suppress NF-kappaB activation induced by a meal. Controversially, 4 weeks of red
      wine consumption compared with de-alcoholized red wine consumption increases the
      oxidative lipid damage marker 8-iso-PGF(2alpha).

PMID- 22859619
TI  - Morphological evidence of an altered process of synaptic transcytosis in adult
      rats exposed to ethanol.
AB  - AIMS: The effects of ethanol exposure on synaptic structure were investigated in
      the nucleus of solitary tract (NST) in rats, using the horse-radish peroxidase
      (HRP) method. METHODS: Eight-week-old experimental rats were allowed free access
      to a liquid diet containing ethanol for 3 weeks, while controls were given an
      isocaloric diet. Some of the control and experimental animals were given an
      injection of wheat germ agglutinin conjugated with HRP (WGA-HRP) into the vagus
      nerve toward the end of the treatment period. After the treatment, the neuropil
      region of the NST was examined under an electron microscope. RESULTS: We observed
      that a few terminals were characterized by deep indentation of axodendritic
      membranes into the post-synaptic neurons. This appeared to be similar to that
      commonly seen in exocrine glands. Interestingly, the indented portion often
      contained various sizes of vacuoles and flattened cisternae. HRP-reaction product
      (RP) transported to terminals was recognized easily as an electron-dense
      lysosomal substance when lead citrate staining was omitted. Terminals containing
      HRP-RP also revealed quite a similar structure with indentation of axodendritic
      membranes as described earlier. The results are considered to confirm that
      terminals forming 'apocrine-like structures' observed in the ethanol-fed animals
      with no injection of WGA-HRP originate from afferent fibers of the vagus nerve.
      CONCLUSION: The present study suggests the possibility that the alteration of the
      synaptic structure induced by ethanol exposure can lead to the neuronal
      transcytosis of materials including proteins which is different from the normal
      vesicular exocytosis involved in chemical synaptic transmission.

PMID- 22859625
TI  - Advancing knowledge translation in primary care.

PMID- 22859626
TI  - Practice-based small group learning programs: systematic review.
AB  - OBJECTIVE: To identify the format, content, and effects of practice-based small
      group learning (PBSGL) programs involving FPs. DATA SOURCES: The Ovid MEDLINE,
      EMBASE, and ERIC databases were searched from inception to the second week of
      November 2011, yielding 99 articles. STUDY SELECTION: Articles were included in
      the analysis if they described the format or content of or evaluated PBSGL
      programs among FPs. Thirteen articles were included in the analysis. SYNTHESIS:
      Two main PBSGL formats exist. The first is self-directed learning, which includes
      review and discussion of troubling or challenging patient cases. The contents of
      such programs vary with different teaching styles. The second format targets
      specific problems from practice to improve certain knowledge or skills or
      implement new guidelines by using patient cases to stimulate discussion of the
      selected topic. Both formats are similar in their ultimate goal, equally
      important, and well accepted by learners and facilitators. Evaluations of
      learners' perceptions and learning outcomes indicate that PBSGL constitutes a
      feasible and effective method of professional development. CONCLUSION: Current
      evidence suggests that PBSGL is a promising method of continuing professional
      development for FPs. Such programs can be adapted according to learning needs.
      Future studies that focus on the changes in practice effected by PBSGL will
      strengthen the evidence for this form of learning and motivate physicians and
      institutions to adopt it.

PMID- 22859627
TI  - Palliation of gastrointestinal obstruction.

PMID- 22859629
TI  - Fish tapeworm and sushi.

PMID- 22859628
TI  - Best thiazide diuretic for hypertension.

PMID- 22859630
TI  - Clerkship pathway: a factor in certification success for international medical
      graduates.
AB  - OBJECTIVE: To identify factors that help predict success for international
      medical graduates (IMGs) who train in Canadian residency programs and pass the
      Canadian certification examinations. DESIGN: A retrospective analysis of 58
      variables in the files of IMGs who applied to the College des medecins du Quebec
      between 2000 and 2008. SETTING: Quebec. PARTICIPANTS: Eight hundred ten IMGs who
      applied to the College des medecins du Quebec through either the "equivalency
      pathway" (ie, starting training at a residency level) or the "clerkship pathway"
      (ie, relearning at the level of a medical student in the last 2 years of the MD
      diploma). MAIN OUTCOME MEASURES: Success factors in achieving certification. Data
      were analyzed using descriptive statistics and ANOVA (analysis of variance).
      RESULTS: International medical graduates who chose the "clerkship pathway" had
      greater success on certification examinations than those who started at the
      residency level did. CONCLUSION: There are several factors that influence IMGs'
      success on certification examinations, including integration issues, the
      acquisition of clinical decision-making skills, and the varied educational
      backgrounds. These factors perhaps can be better addressed by a regular clerkship
      pathway, in which IMGs benefit from learner-centred teaching and have more time
      for reflection on and understanding of the North American approach to medical
      education. The clerkship pathway is a useful strategy for assuring the
      integration of IMGs in the North American health care system. A 2-year relearning
      period in medical school at a clinical clerkship level deserves careful
      consideration.

PMID- 22859631
TI  - Residency research requirements and the CanMEDS-FM scholar role: perspectives of
      residents and recent graduates.
AB  - OBJECTIVE: To explore the perspectives of family medicine residents and recent
      family medicine graduates on the research requirements and other CanMEDS scholar
      competencies in family practice residency training. DESIGN: Semistructured focus
      groups and individual interviews. SETTING: Family practice residency program at
      the University of British Columbia in Vancouver. PARTICIPANTS: Convenience sample
      of 6 second-year family medicine residents and 6 family physicians who had
      graduated from the University of British Columbia family practice residency
      program within the previous 5 years. METHODS: Two focus groups with residents and
      individual interviews with each of the 6 recently graduated physicians. All
      interviews were audiotaped, transcribed, and analyzed for thematic content. MAIN
      FINDINGS: Three themes emerged that captured key issues around research
      requirements in family practice training: 1) relating the scholar role to family
      practice, 2) realizing that scholarship is more than simply the creation or
      discovery of new knowledge, and 3) addressing barriers to integrating research
      into a clinical career. CONCLUSION: Creation of new medical knowledge is just one
      aspect of the CanMEDS scholar role, and more attention should be paid to the
      other competencies, including teaching, enhancing professional activities through
      ongoing learning, critical appraisal of information, and learning how to better
      contribute to the dissemination, application, and translation of knowledge.
      Research is valued as important, but opinions still vary as to whether a formal
      research study should be required in residency. Completion of residency research
      projects is viewed as somewhat rewarding, but with an equivocal effect on future
      research intentions.

PMID- 22859632
TI  - Implementing an evidence-informed faculty development program.
AB  - OBJECTIVE: To establish an evidence-informed faculty development program. DESIGN:
      Survey derived from a needs-assessment tool. SETTING: Department of Academic
      Family Medicine at the University of Saskatchewan, which is geographically
      dispersed across the province. PARTICIPANTS: Full-time faculty members in the
      Department of Academic Family Medicine at the University of Saskatchewan. MAIN
      OUTCOME MEASURES: Creation of an evidence-informed faculty development program.
      RESULTS: The response rate was 77.3% (17 of 22). The data were stratified by 2
      groups: faculty members with less than 5 years of experience and those with 5 or
      more years of experience. Those with less than 5 years of experience rated the
      following as their top priorities: teaching, developing scholarly activities, and
      career development. Those with 5 or more years of experience rated the following
      as their top priorities: administration and leadership, teaching, and information
      technology. Although there were differences in overall priorities, the 2 groups
      identified 17 out of 54 skills as important to faculty development. CONCLUSION:
      The results of the needs-assessment tool were used to shape a dynamic, evidence
      informed faculty development program with full-time faculty in the Department of
      Academic Family Medicine at the University of Saskatchewan. Future programs will
      continue to be dynamic, faculty-centred, and evidence-informed.

PMID- 22859634
TI  - Obesity must be addressed.

PMID- 22859635
TI  - Dermoscopy for melanoma detection in family practice.
AB  - OBJECTIVE: To assess the diagnostic accuracy and clinical utility of dermoscopy
      for melanoma detection in family practice. QUALITY OF EVIDENCE: Ovid MEDLINE
      (1946 to June 2011), EMBASE, PubMed, and Cochrane databases were searched using
      the following terms: dermoscopy, dermatoscopy, epiluminescence microscopy, family
      practice, general practice, primary health care, melanoma, skin neoplasms, and
      pigmented nevus. To be included, studies had to be primary research articles with
      family physicians as the subjects and dermoscopy training and use as the
      intervention. Four papers met all inclusion criteria and provided level I
      evidence according to the Canadian Task Force on Preventive Health Care
      definition. MAIN MESSAGE: Among family physicians, dermoscopy has higher
      sensitivity for melanoma detection than naked-eye examination with generally no
      decrease in specificity. Dermoscopy also helps to increase family physicians'
      confidence in their preliminary diagnosis of lesions. When using dermoscopy,
      compared with naked-eye examination, there is a higher likelihood that a lesion
      assessed as being malignant is in fact malignant and that a lesion assessed as
      being benign is in fact benign. CONCLUSION: Dermoscopy has been shown to be a
      useful and fairly inexpensive tool for melanoma detection in family practice.
      This technique can increase family physicians' confidence in their referral
      accuracy to dermatologists and can assist in decreasing unnecessary biopsies.
      Dermoscopy might be especially useful in examining patients at high risk of
      melanoma, as the current Canadian clinical practice guideline recommends yearly
      screening in these individuals.

PMID- 22859636
TI  - Topical nonsteroidal anti-inflammatory drugs for corneal abrasions in children.
AB  - QUESTION: Corneal abrasion from minor injury to the eye is common in both adults
      and children. Some of my colleagues prescribe topical nonsteroidal anti
      inflammatory drugs (NSAIDs) for analgesia. How safe is this practice? ANSWER:
      Topical ophthalmic NSAIDs are a short-term effective treatment of the pain
      associated with corneal abrasions in children. Rare but serious complications
      have been reported in adult case-study series. Children with corneal abrasions
      should have follow-up appointments within 24 to 48 hours to assess healing,
      complications, and side effects of treatment, particularly if they are using
      topical NSAIDs.

PMID- 22859637
TI  - Don't you forget about me: considering acute rhabdomyolysis in ED patients with
      cocaine ingestion.

PMID- 22859638
TI  - Bioidentical hormone micronized progesterone.

PMID- 22859639
TI  - Bilateral spontaneous persistent open pneumothorax with chylothorax.

PMID- 22859640
TI  - Physical activity in chronic respiratory conditions: assessing risks for physical
      activity clearance and prescription.

PMID- 22859641
TI  - Improving the diagnosis of asthma in a primary care practice.

PMID- 22859642
TI  - Evaluating practice patterns for managing moderate to severe plaque psoriasis:
      role of the family physician.
AB  - OBJECTIVE: To describe practice patterns for care of Canadian patients with
      moderate to severe plaque psoriasis. DESIGN: Online survey of a consumer panel.
      SETTING: Participants were drawn from a population-wide Canadian consumer
      database. PARTICIPANTS: To be eligible to participate, respondents had to have
      been diagnosed with plaque psoriasis within the past 5 years, and to have had
      body surface area involvement of 3% or greater in the past 5 years, or to have
      psoriasis on a sensitive area of the body (hands, feet, scalp, face, or
      genitals), or to be currently receiving treatment with systemic agents or
      phototherapy for psoriasis. MAIN OUTCOME MEASURES: Proportion of respondents with
      psoriasis managed by FPs and other specialists, psoriasis therapies,
      comorbidities, and patient satisfaction. RESULTS: Invitations were sent to 3845
      panelists with self-reported psoriasis, of which 514 qualified to complete the
      survey. Family physicians were reported to be the primary providers for diagnosis
      and ongoing care of psoriasis in all provinces except Quebec. Overall physician
      care was reported to be satisfactory by 62% of respondents. Most respondents
      receiving over-the-counter therapies (55%) or prescribed topical therapies (61%)
      reported that their psoriasis was managed by FPs. Respondents receiving
      prescription oral or injectable medications or phototherapy were mainly managed
      by dermatologists (42%, 74%, and 71% of respondents, respectively). Ongoing
      management of respondents with body surface area involvement of 10% or greater
      was mainly split between dermatologists (47%) and FPs (45%), compared with
      rheumatologists (4%) or other health care professionals (4%). Of those
      respondents receiving medications for concomitant health conditions, treatment
      for high blood pressure was most common (92%), followed by treatment for heart
      disease (75%) and elevated cholesterol and lipid levels (68%). CONCLUSION:
      Patient-reported practice patterns for the diagnosis and management of moderate
      to severe psoriasis vary among provinces and in primary and secondary care
      settings.

PMID- 22859643
TI  - Validation of a large-scale clinical examination for international medical
      graduates.
AB  - OBJECTIVE: To evaluate a new examination process for international medical
      graduates (IMGs) to ensure that it is able to reliably assign candidates to 1 of
      4 competency levels, and to determine if a global rating scale can accurately
      stratify examinees into 4 levels of learners: clerks, first-year residents,
      second-year residents, or practice ready. DESIGN: Validation study evaluating a
      12-station objective structured clinical examination. SETTING: Ontario.
      PARTICIPANTS: A total of 846 IMGs, and an additional 63 randomly selected
      volunteers from 2 groups: third-year clinical clerks (n = 42) and first-year
      family medicine residents (n = 21). MAIN OUTCOME MEASURES: The accuracy of the
      stratification of the examinees into learner levels, the impact of the patient
      encounter ratings and postencounter oral questions, and between-group differences
      in total score. RESULTS: Reliability of the patient-encounter scores,
      postencounter oral question scores, and the total between-group difference scores
      was 0.93, 0.88, and 0.76, respectively. Third-year clerks scored the lowest,
      followed by the IMGs. First-year residents scored highest for all 3 scores.
      Analysis of variance demonstrated significant between-group differences for all 3
      scores (P < .05). Postencounter oral question scores differentiated among all 3
      groups. CONCLUSION: Clinical examination scores were capable of differentiating
      among the 3 groups. As a group, the IMGs seemed to be less competent than the
      first-year family medicine residents and more competent than the third-year
      clerks. The scores generated by the postencounter oral questions were the most
      effective in differentiating between the 2 training levels and among the 3 groups
      of test takers.

PMID- 22859644
TI  - Privacy protection and public goods: building a genetic database for health
      research in Newfoundland and Labrador.
AB  - OBJECTIVE: To provide a legal and ethical analysis of some of the implementation
      challenges faced by the Population Therapeutics Research Group (PTRG) at Memorial
      University (Canada), in using genealogical information offered by individuals for
      its genetics research database. MATERIALS AND METHODS: This paper describes the
      unique historical and genetic characteristics of the Newfoundland and Labrador
      founder population, which gave rise to the opportunity for PTRG to build the
      Newfoundland Genealogy Database containing digitized records of all pre
      confederation (1949) census records of the Newfoundland founder population. In
      addition to building the database, PTRG has developed the Heritability Analytics
      Infrastructure, a data management structure that stores genotype, phenotype, and
      pedigree information in a single database, and custom linkage software (KINNECT)
      to perform pedigree linkages on the genealogy database. DISCUSSION: A newly
      adopted legal regimen in Newfoundland and Labrador is discussed. It incorporates
      health privacy legislation with a unique research ethics statute governing the
      composition and activities of research ethics boards and, for the first time in
      Canada, elevating the status of national research ethics guidelines into law. The
      discussion looks at this integration of legal and ethical principles which
      provides a flexible and seamless framework for balancing the privacy rights and
      welfare interests of individuals, families, and larger societies in the creation
      and use of research data infrastructures as public goods. CONCLUSION: The
      complementary legal and ethical frameworks that now coexist in Newfoundland and
      Labrador provide the legislative authority, ethical legitimacy, and practical
      flexibility needed to find a workable balance between privacy interests and
      public goods. Such an approach may also be instructive for other jurisdictions as
      they seek to construct and use biobanks and related research platforms for
      genetic research.

PMID- 22859645
TI  - Large-scale evaluation of automated clinical note de-identification and its
      impact on information extraction.
AB  - OBJECTIVE: (1) To evaluate a state-of-the-art natural language processing (NLP)
      based approach to automatically de-identify a large set of diverse clinical
      notes. (2) To measure the impact of de-identification on the performance of
      information extraction algorithms on the de-identified documents. MATERIAL AND
      METHODS: A cross-sectional study that included 3503 stratified, randomly selected
      clinical notes (over 22 note types) from five million documents produced at one
      of the largest US pediatric hospitals. Sensitivity, precision, F value of two
      automated de-identification systems for removing all 18 HIPAA-defined protected
      health information elements were computed. Performance was assessed against a
      manually generated 'gold standard'. Statistical significance was tested. The
      automated de-identification performance was also compared with that of two humans
      on a 10% subsample of the gold standard. The effect of de-identification on the
      performance of subsequent medication extraction was measured. RESULTS: The gold
      standard included 30 815 protected health information elements and more than one
      million tokens. The most accurate NLP method had 91.92% sensitivity (R) and
      95.08% precision (P) overall. The performance of the system was indistinguishable
      from that of human annotators (annotators' performance was 92.15%(R)/93.95%(P)
      and 94.55%(R)/88.45%(P) overall while the best system obtained
      92.91%(R)/95.73%(P) on same text). The impact of automated de-identification was
      minimal on the utility of the narrative notes for subsequent information
      extraction as measured by the sensitivity and precision of medication name
      extraction. DISCUSSION AND CONCLUSION: NLP-based de-identification shows
      excellent performance that rivals the performance of human annotators.
      Furthermore, unlike manual de-identification, the automated approach scales up to
      millions of documents quickly and inexpensively.

PMID- 22859646
TI  - The BioIntelligence Framework: a new computational platform for biomedical
      knowledge computing.
AB  - Breakthroughs in molecular profiling technologies are enabling a new data
      intensive approach to biomedical research, with the potential to revolutionize
      how we study, manage, and treat complex diseases. The next great challenge for
      clinical applications of these innovations will be to create scalable
      computational solutions for intelligently linking complex biomedical patient data
      to clinically actionable knowledge. Traditional database management systems
      (DBMS) are not well suited to representing complex syntactic and semantic
      relationships in unstructured biomedical information, introducing barriers to
      realizing such solutions. We propose a scalable computational framework for
      addressing this need, which leverages a hypergraph-based data model and query
      language that may be better suited for representing complex multi-lateral, multi
      scalar, and multi-dimensional relationships. We also discuss how this framework
      can be used to create rapid learning knowledge base systems to intelligently
      capture and relate complex patient data to biomedical knowledge in order to
      automate the recovery of clinically actionable information.

PMID- 22859647
TI  - Identification of seven water-soluble non-storage proteins from pomegranate
      (Punica granatum Linn.) seeds.
AB  - As pomegranate (Punica granatum Linn.) processing is fast growing, the usage of
      pomegranate processing wastes containing seeds has been receiving great
      attention. The protein component accounts for 100-130 g/kg of the seeds in
      weight. However, so far, there is no information on the composition and function
      of the pomegranate seed proteins. In this study, a global view of water-soluble
      non-storage proteins isolated from mature pomegranate seeds were studied using
      two-dimensional polyacrylamide gel electrophoresis coupled with liquid
      chromatography-tandem mass spectrometry. With the two-dimensional polyacrylamide
      gel electrophoresis approach, over 120 protein spots were resolved, of which 7
      abundant protein spots showing low molecular mass were identified. These
      identified proteins may be linked to seed development and metabolism, but more
      importantly, the occurrence of these proteins provides the possibility of
      conversion the pomegranate processing wastes into useful products or raw material
      for food industry.

PMID- 22859648
TI  - Development of quality index method for anchovy (Engraulis anchoita) stored in
      ice: assessment of its shelf-life by chemical and sensory methods.
AB  - The objective of this study was to develop a quality index method for Engraulis
      anchoita stored in ice and to determine its shelf-life based on this quality
      index method and chemical indices such as total volatile bases and thiobarbituric
      acid-reactive substances. Besides, the chemical composition with emphasis on the
      polyunsaturated fatty acids content was determined. The results indicate that E.
      anchoita is a valuable protein source and lipid with important content of n-3
      polyunsaturated fatty acids. The developed quality index method scheme was
      composed of 28 demerit points, divided into 4 parameters and 10 attributes. All
      attributes showed correlation with time of storage (R > 0.90). The quality index
      (QI) presented a linear relationship with storage (QI = 2.55x days in ice + 1.76;
      R2= 0.98). In the shelf-life assessment-based quality index method, the rejection
      sensory point was observed after 7 days of storage due to the presence of
      unpleasant odours and deteriorated appearance. The total volatile basic nitrogen
      value remained below the upper limit of acceptability during the 10 days of ice
      storage. The evolution of thiobarbituric acid-reactive substances indicates
      lipids oxidation during the storage of anchovies. According to the results, the
      quality index method scheme developed for the E. anchoita stored in ice could be
      considered adequate to evaluate their freshness and to estimate its shelf-life.

PMID- 22859649
TI  - Quality, stability and radical scavenging activity of olive oils after Chetoui
      olives (Olea europaea L.) storage under modified atmospheres.
AB  - At the industrial scale, the major source of olive oil deterioration is the poor
      handling of the raw material during the time separating harvesting from
      processing. The objective of this work was to verify the effect of modified
      atmospheres and cold storage in relation to quality parameters of the extracted
      oils. Olives (cv Chetoui) intended for oil extraction, were stored for 21 days at
      two different temperatures (ambient temperature 14 +/- 2  degrees C and 5 
      degrees C) and under two different modified atmospheres 21% O2 - 0% CO2 and 2% O2
      - 5% CO2. Oils quality was ascertained with analytical parameters: free fatty
      acids, peroxide value, K232, K270 as suggested by European regulation. Oxidative
      stability, total phenols content, radical scavenging activity and fatty acids
      composition were carried out in order to measure the hydrolytic and oxidative
      degradation of oils. Olive oils quality parameters were significantly affected by
      treatments with especially a beneficial effect on primary oxidation indicators
      and free acidity. Most efficient treatments, with regard to oils phenolic content
      and involved parameters, were 21% O2 - 0% CO2 at ambient temperature (636.25 mg
      ca/kg) and 2% O2 - 5% CO2 under 5  degrees C (637.50 mg ca/kg). Those two
      treatments improved individually oil samples phenolic content of 25% but not at
      the same storage period.

PMID- 22859650
TI  - Physicochemical and sensory properties of yogurt enriched with microencapsulated
      fish oil.
AB  - Encapsulation of marine omega-3 oil by complex coacervation technique has been
      introduced as most effective approach to delay its oxidation and extend shelf
      life of omega(3)-enriched food products. Therefore, to produce enriched yogurt,
      fish oil containing long-chain omega-3 polyunsaturated fatty acids was
      microencapsulated in complex coacervates of gelatin/acacia gum. Then, the
      microcapsules were dried and their surface oil was extracted. Set yogurt was
      prepared by enriched milk with microcapsules powder. Physicochemical and sensory
      properties of enriched yogurt were measured during 21 days storage. Acidity,
      apparent viscosity and water holding capacity of enriched samples were higher and
      gel strength and amount of whey separation were lower compared to the control.
      The enriched yogurt samples were more yellowish compared to control. The peroxide
      value of free and encapsulated fish oil in enriched yogurt samples, after 22 days
      storage, were increased to 72% and 260%, respectively. Fish oil release of
      microcapsules was not detected by gas chromatography in extracted oil from
      enriched yogurt. Sensory results showed that untrained panelists evaluated
      overall acceptance of enriched yogurt with treated-fish oil microcapsules by lime
      juice as 'neither liked nor disliked to slightly liked'.

PMID- 22859651
TI  - Quality, microstructure, biochemical and immunochemical characteristics of
      hypoallergenic pasta.
AB  - Celiac disease is an immune-mediated enteropathy, characterized by lifelong
      intolerance to gluten in genetically susceptible individuals. This study aims to
      develop hypoallergenic pasta using blends of Triticum durum semolina, 40% of
      other non-wheat flours and additives. Formulated pasta samples were evaluated for
      product quality characteristics and also subjected to biochemical analysis.
      Results showed that cooking loss ranged from 6.9% to 7.4%, which were within the
      acceptable range of 8%. Color change was low and in vitro protein digestibility
      of the pasta was found to be insignificant. Pasting characteristics of the
      hypoallergenic flour showed the increased peak viscosity and decreased
      gelatinization temperature. The scanning electron microscopy results demonstrated
      less-affected microstructure of gluten network. Texture profile analysis and
      descriptive sensory analysis revealed that optimized hypoallergenic pasta with
      xanthan gum as additive was acceptable and comparable with control. SDS-PAGE
      pattern showed distinct protein profile and decreased intensity, which was
      supported by Dot-Blot. In conclusion, the hypoallergenic pasta prepared by
      replacing T durum flour by 40% of other non-gluten flours could be useful for
      celiac patients because of its low antigenic activity.

PMID- 22859652
TI  - The fossil record of Eucalyptus in Patagonia.
AB  - PREMISE OF THE STUDY: Herein, we name, describe, and illustrate new macrofossil
      material representing Eucalyptus (Myrtaceae: Myrtoideae, Eucalypteae) from the
      diverse early Eocene Laguna del Hunco (LH) flora of Chubut Province, Patagonia,
      Argentina. We explore the significance of these fossils in light of understanding
      the fossil record of eucalypts and the biogeography of the Eucalypteae. METHODS:
      Fossils representing vegetative and reproductive organs were collected from
      multiple LH localities over several field seasons. These specimens were prepared,
      photographed, and compared to extant Eucalyptus. Additional historical
      collections of Patagonian fossil Eucalyptus were also examined. KEY RESULTS:
      Vegetative and reproductive organs representing five different Eucalyptus taxa
      were identified in the LH paleoflora. One new taxon each representing leaves,
      flower buds, and infructescences with co-occurring, isolated capsules are
      described and named as new Eucalyptus species. Additionally, two flower types cf.
      Eucalyptus, represented by one specimen each, are illustrated and briefly
      described. The fossil species have unique characteristics that independently
      suggest each belongs within the Eucalypteae. The reproductive material is most
      similar morphologically to extant Eucalyptus, although it also shares many
      similarities to the closely related genus Corymbia. CONCLUSIONS: The LH fossil
      Eucalyptus material is among the few eucalypt macrofossils that have recently
      been named and described and are the oldest macrofossils that can presently be
      definitively ascribed to the Eucalypteae. They also represent the only credible
      description of Eucalyptus fossils occurring outside of Australasia and suggest a
      once broader geographic distribution for this group.

PMID- 22859653
TI  - Effects of inbreeding and interpopulation crosses on performance and plasticity
      of two generations of offspring of a declining grassland plant.
AB  - PREMISE OF THE STUDY: Inbreeding depression is a major evolutionary force and an
      important topic in conservation genetics because habitat fragmentation leads to
      increased inbreeding in the populations of many species. Crosses between
      populations may restore heterozygosity, resulting in increased performance
      (heterosis), but may also lead to the disruption of coadapted gene complexes and
      to decreased performance (outbreeding depression). METHODS: We investigated the
      effects of selfing and of within and between population crosses on reproduction
      and the performance of two generations of offspring of the declining grassland
      plant Saxifraga granulata (Saxifragaceae). We also subjected the first generation
      of offspring to a fertilization and two stress treatments (competition and
      defoliation) to investigate whether the effects of inbreeding and interpopulation
      gene flow depend on environmental conditions. KEY RESULTS: Inbreeding depression
      affected all traits in the F(1) generation (delta = 0.07-0.55), but was stronger
      for traits expressed late during development and varied among families. The
      adaptive plasticity of offspring from selfing and from interpopulation crosses in
      response to nutrient addition was reduced. Outbreeding depression was also
      observed in response to stress. Multiplicative fitness of the F(2) generation
      after serial inbreeding was extremely low (delta > 0.99), but there was heterosis
      after crossing inbred lines. Outbreeding depression was not observed in the F(2).
      CONCLUSIONS: Continuous inbreeding may drastically reduce the fitness of plants,
      but effects may be environment-dependent. When assessing the genetic effects of
      fragmentation and interpopulation crosses, the possible effects on the mean
      performance of offspring and on its adaptive plasticity should be considered.

PMID- 22859654
TI  - Molecular phylogenetics of Echinopsis (Cactaceae): Polyphyly at all levels and
      convergent evolution of pollination modes and growth forms.
AB  - PREMISE OF THE STUDY: In its current circumscription, Echinopsis with 100-150
      species is one of the largest and morphologically most diverse genera of
      Cactaceae. This diversity and an absence of correlated characters have resulted
      in numerous attempts to subdivide Echinopsis into more homogeneous subgroups. To
      infer natural species groups in this alliance, we here provide a plastid
      phylogeny and use it to infer changes in growth form, pollination mode, and
      ploidy level. METHODS: We sequenced 3800 nucleotides of chloroplast DNA from 162
      plants representing 144 species and subspecies. The sample includes the type
      species of all genera close to, or included in, Echinopsis as well as a dense
      sample of other genera of the Trichocereeae and further outgroups. New and
      published chromosome counts were compiled and traced on the phylogeny, as were
      pollination modes and growth habits. KEY RESULTS: A maximum likelihood phylogeny
      confirms that Echinopsis s.l. is not monophyletic nor are any of the previously
      recognized genera that have more than one species. Pollination mode and, to a
      lesser extent, growth habit are evolutionarily labile, and diploidy is the rule
      in Echinopsis s.l., with the few polyploids clustered in just a few clades.
      CONCLUSIONS: The use of evolutionary labile floral traits and growth habit has
      led to nonnatural classifications. Taxonomic realignments are required, but
      further study of less evolutionary labile traits suitable for circumscribing
      genera are needed. Surprisingly, polyploidy seems infrequent in the Echinopsis
      alliance and hybridization may thus be of minor relevance in the evolution of
      this clade.

PMID- 22859655
TI  - Variation in ploidy level and phenology can result in large and unexpected
      differences in demography and climatic sensitivity between closely related ferns.
AB  - PREMISE OF THE STUDY: Current environmental changes may affect the dynamics and
      viability of plant populations. This environmental sensitivity may differ between
      species of different ploidy level because polyploidization can influence life
      history traits. We compared the demography and climatic sensitivity of two
      closely related ferns: the tetraploid Polystichum aculeatum and one of its
      diploid parents, Polystichum setiferum. METHODS: Matrix models were used to
      assess the effects of life history variation on population dynamics under varying
      winter conditions. We analyzed the contributions of all key aspects of the fern
      life cycle to population growth. Our study is the first to also include the
      gametophyte generation. KEY RESULTS: Projected population growth rate (lambda)
      was much higher for the tetraploid P. aculeatum (1.516) than for P. setiferum
      (1.071) under normal winter conditions. During a year with harsh winter
      conditions, population growth of P. aculeatum was strongly reduced. This finding
      contradicts our expectation that the winter-hardy fronds of this species would
      allow high survival of harsh winters. Differences in lambda between species and
      between years with different winter conditions were mostly caused by variation in
      gametophyte-related recruitment rates, a finding that shows the importance of
      including gametophytes in fern demographic studies. CONCLUSIONS: Our results
      indicate that populations of closely related ferns can show large differences in
      population performance, mainly related to recruitment rates and frond phenology,
      and that these differences may depend greatly on climatic conditions. Our
      findings provide a first indication that (allo)polyploidization in ferns can have
      a significant effect on population dynamics.

PMID- 22859656
TI  - Microsatellite primers in Oenothera harringtonii (Onagraceae), an annual endemic
      to the shortgrass prairie of Colorado.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed in the annual herb,
      Oenothera harringtonii, to investigate patterns of genetic diversity, gene flow,
      and parentage within and among populations of this Colorado endemic. METHODS AND
      RESULTS: Ten polymorphic loci were identified in O. harringtonii and tested in
      four populations sampled across the range of the species. These loci contained
      trinucleotide repeats with 7-29 alleles per locus. Nine of the 10 loci also
      amplified in O. caespitosa subsp. macroglottis, O. caespitosa subsp. marginata,
      and O. caespitosa subsp. navajoensis. In addition, we optimized three markers
      developed for O. biennis and provide reports of their effectiveness in all four
      taxa. CONCLUSIONS: These results indicate the utility of these markers in O.
      harringtonii for future studies of genetic structure, gene flow, and parentage as
      well as their applicability in other members of the O. caespitosa species
      complex.

PMID- 22859657
TI  - Isolation and characterization of microsatellite markers for Thujopsis dolabrata
      var. hondai (Cupressaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the endemic
      Japanese species Thujopsis dolabrata var. hondai for studies on forest ecology
      and tree breeding. METHODS AND RESULTS: We characterized 10 dinucleotide
      microsatellite loci by screening primers developed using a simple sequence repeat
      enriched library. The number of alleles per locus ranged from eight to 44 with an
      average of 20.3. The observed and expected heterozygosities ranged from 0.326 to
      0.854 and from 0.670 to 0.976, respectively. CONCLUSIONS: The development of
      these markers can be used to assess useful genetic information for ecological
      studies and tree breeding in T. dolabrata var. hondai.

PMID- 22859658
TI  - Does inbreeding promote evolutionary reduction of flower size? Experimental
      evidence from Crepis tectorum (Asteraceae).
AB  - PREMISE OF THE STUDY: Small, autogamous flowers have evolved repeatedly in the
      plant kingdom. While much attention has focused on the mechanisms that promote
      the shift to autogamy, there is still a paucity of information on the factors
      that underlie the reduction of flower size so prevalent in selfing lineages. In
      this study of Crepis tectorum, I examine the role of inbreeding, acting alone or
      together with selection, in promoting evolutionary reduction of flower size.
      METHODS: Experimental crosses were performed to produce progeny populations that
      differed in inbreeding and (or) selection history. Progenies were grown in two
      different environments and scored for flower size and other characters. KEY
      RESULTS: Inbreeding depressed flower and fruit size, but also caused changes in
      flowering time and the number of heads produced. Despite some inconsistencies in
      the results for the last progeny generation, the decline in flower size was
      persistent over generations, consistent across environments, and similar in
      magnitude to the effects of selection for small flower size and the floral
      reduction inferred to have taken place during the shift toward autogamy within
      the study species. The floral size reduction was largely independent of changes
      in overall vigor, and there was considerable adaptive potential in flower size
      (measured by sib analyses and parent-offspring comparisons) after inbreeding.
      CONCLUSIONS: The results of this study indicate that inbreeding can promote
      evolutionary reduction of flower size and highlight the close, persistent
      association between flower and fruit size in the study species.

PMID- 22859659
TI  - Comments on 'oxidative stress increases in carbon monoxide poisoning'.

PMID- 22859660
TI  - Effects of fenofibrate, a PPAR-alpha ligand, on the haemodynamics of glycerol
      induced renal failure in rats.
AB  - The modulating effect of peroxisome proliferator-activated receptor alpha ligand
      on haemodynamic effects of phenylepherine (PE), angiotensin II (AII), endothelin
      1 (ET1), acetylcholine (Ach), sodium nitroprusside (SNP) and isoproterenol (ISO)
      were evaluated in glycerol-induced acute kidney injury in rats. The effect of PE
      on fenofibrate-treated animals was a dose-dependent increase in mean arterial
      blood pressure (MAP). For AII and ET1, MAP was also increased for the fenofibrate
      group but not in a dose-dependent fashion. On the medullary blood flow (MBF),
      while the lower doses of PE and AII increased the perfusion unit on the
      fenofibrate-treated group, the higher doses decreased the perfusion unit. The ET1
      increased the perfusion unit on this group but not in dose-dependent fashion. The
      effects of PE and AII on the cortical blood flow (CBF) of fenofibrate-treated
      group is similar to that of MBF for the same group but not for ET1. The effect of
      Ach, SNP and ISO in all the groups was the decrease in MAP. ISO caused dose
      dependent increase in MBF of fenofibrate-treated group. The effect of Ach, SNP
      and ISO on the CBF perfusion unit was that of the increase for the fenofibrate
      treated group. The study showed that fenofibrate did not attenuate increased
      blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by
      Ach, SNP and ISO.

PMID- 22859661
TI  - Combined effects of treatment with vitamin C, vitamin E and selenium on the skin
      of diabetic rats.
AB  - The aim of this study was to investigate the effects of vitamin C, vitamin E and
      selenium (Se) on the skin tissue of streptozotocin-induced diabetic rats. Swiss
      albino rats were divided into four groups: control, control + antioxidants,
      diabetic, diabetic + antioxidants groups. Diabetes was induced by intraperitoneal
      injection of 65 mg/kg streptozotocin. Vitamin C (250 mg/kg), vitamin E (250
      mg/kg) and Se (0.2 mg/kg) were given by gavage technique to rats of one diabetic
      and one control group for 30 days. In the diabetic group, the levels of serum
      urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation
      levels increased, but skin glutathione levels decreased. Treatment with vitamin
      C, vitamin E and Se reversed these effects. The present study showed that vitamin
      C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin
      damage caused by streptozotocin-induced diabetes.

PMID- 22859662
TI  - Synthetic cannabinoid and marijuana exposures reported to poison centers.
AB  - Synthetic cannabinoids have recently gained popularity as a recreational drug
      because they are believed to result in a marijuana-like high. This investigation
      compared synthetic cannabinoids and marijuana exposures reported to a large
      statewide poison center system. Synthetic cannabinoid and marijuana exposures
      reported to Texas poison centers during 2010 were identified. The distribution of
      exposures to the two agents with respect to various demographic and clinical
      factors were compared by calculating the rate ratio (RR) of the synthetic
      cannabinoid and marijuana percentages for each subgroup and 95% confidence
      interval (CI). The proportion of synthetic cannabinoid and marijuana exposures,
      respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38-2.61),
      74.9% and 65.7% in male (RR 1.14, 95% CI 0.87-1.51), 40.2% and 56.6% age <= 19
      years (RR 0.71, 95% CI 0.52-0.98), 79.2% and 58.6% occurring at a residence (RR
      1.35, 95% CI 1.02-1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28
      1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03
      2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to
      be used through inhalation, to involve adults, to be used at a residence, and to
      result in serious outcomes.

PMID- 22859663
TI  - Prognostic significance of the containment and location of osteochondral lesions
      of the talus: independent adverse outcomes associated with uncontained lesions of
      the talar shoulder.
AB  - BACKGROUND: Uncontained osteochondral lesions of the talar shoulder are
      associated with an increased risk of clinical failure in patients treated with
      current cylindrical osteochondral autograft techniques. Whether the same holds
      true in patients undergoing arthroscopic treatment is unknown. PURPOSE: To
      determine the relative prognostic significance of the containment (shoulder vs
      nonshoulder type) and location (medial vs lateral) of an osteochondral lesion of
      the talus (OLT). HYPOTHESIS: Arthroscopic treatment may not be ideal for
      uncontained lesions of the talar shoulder due to a lack of structural support.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Arthroscopic treatment
      for OLT was performed on the ankles of 399 patients between 2001 and 2009.
      Analyses were performed by grouping the patients according to type of containment
      (shoulder, n = 181; nonshoulder, n = 218), location (medial, n = 274; lateral, n
      = 125), and both type of containment and location (medial shoulder, n = 129;
      medial nonshoulder, n = 145; lateral shoulder, n = 52; lateral nonshoulder, n =
      73). To evaluate the role of containment and location independently of OLT size,
      patients were grouped according to quartile of defect size, and outcomes were
      analyzed within each group. RESULTS: Patients with shoulder-type OLT had a
      substantially worse clinical outcome than did those with nonshoulder-type OLT,
      even after adjustment for OLT size (P < .05). However, there was no significant
      difference in clinical outcome between patients with medial OLT and those with
      lateral OLT, and the clinical failure rates of the 2 groups were similar (P >
      .05). A Cox proportional hazards regression model demonstrated that OLT
      containment, but not location, exerted an independent prognostic effect.
      CONCLUSION: Patients with uncontained OLT of the talar shoulder experienced a
      more complicated clinical outcome than did those with contained, nonshoulder-type
      OLT even after adjustment for OLT size and regardless of location.

PMID- 22859664
TI  - Assessing empathy in Salvadoran high-risk and gang-involved adolescents and young
      adults: a Spanish validation of the basic empathy scale.
AB  - Empathy is considered a key construct in the empirical study of high-risk
      adolescent and young adult delinquency, crime, and violence. This study examined
      the psychometric properties and criterion-related validity of a Spanish
      adaptation of the Basic Empathy Scale (BES), which is an important measure
      designed to capture both affective and cognitive empathy that has been validated
      in multiple languages but not in Spanish. The study's sample consisted of 208
      high-risk and gang-involved adolescents and young adults in the Greater San
      Salvador Metropolitan Area. The original BES was reduced from its 20-item design
      to a more culturally appropriate 7-item design. The results of the confirmatory
      factor analysis and criterion-related validity analysis indicate that the adapted
      BES is a valid and reliable multidimensional measure of empathy for high-risk
      Salvadoran adolescents and young adults. Consistent with previous findings,
      females reported lower levels of empathy than males and delinquent/violent
      respondents reported lower levels of empathy than their nonoffender counterparts.

PMID- 22859665
TI  - Parenting, self-control, and the gender gap in heavy drinking: the case of
      Russia.
AB  - Drawing on Gottfredson and Hirschi's theory linking parenting to deviant behavior
      via development of self-control, the authors assess the association between
      parenting styles, self-control ability, and frequent alcohol use separately for
      males and females. The authors' findings from a random sample of 440 Russian
      respondents provide mixed support for self-control theory. Contrary to the
      theory, but in line with extant research, the authors failed to uncover
      significant gender differences in childhood upbringing or establish a strong link
      between parenting techniques and self-control. Furthermore, whereas parental
      upbringing appears to increase the likelihood of frequent drinking among men,
      self-control does not mediate this relationship but rather acts as an independent
      predictor of men's alcohol abuse. Finally, the relatively modest contribution of
      self-control differences to the gender gap in frequent drinking suggests that
      higher alcohol consumption among men likely stems from alternative, possibly
      context-embedded factors.

PMID- 22859666
TI  - Knocking out viral myocarditis: reality or a miRage?

PMID- 22859667
TI  - A new pROM king for the mitoK(ATP) dance: ROMK takes the lead.

PMID- 22859668
TI  - Promoting atherosclerosis in type 1 diabetes through the selective activation of
      arachidonic acid and PGE(2) production.
AB  - Type 1 diabetics harbor a greatly elevated risk for progressive atherosclerosis
      and cardiovascular events, but the mechanistic basis for this phenomenon is not
      entirely clear. Although this link is likely to involve many factors, the
      specific activation of a lipid-driven inflammatory phenotype in monocytes and
      macrophages of people with type 1 diabetes is an attractive causal mechanism, due
      to the ability of inflamed macrophages to exacerbate plaque deposition,
      expansion, and instability.

PMID- 22859669
TI  - Cardiac P2X(4) receptors: targets in ischemia and heart failure?
AB  - Purinergic receptors have attracted growing interest as therapeutic targets. This
      perspective focuses on P2X(4) receptors as a new cardioprotective target in heart
      failure.

PMID- 22859671
TI  - "Good enough solutions" and the genetics of complex diseases.
AB  - In this Emerging Science Review, we discuss a systems genetics strategy, which we
      call gene module association study (GMAS), as a novel approach complementing
      genome-wide association studies (GWAS), to understand complex diseases by
      focusing on how genes work together in groups rather than singly. The first step
      is to characterize phenotypic differences among a genetically diverse population.
      The second step is to use gene expression microarray (or other high-throughput)
      data from the population to construct gene coexpression networks. Coexpression
      analysis typically groups 20 000 genes into 20 to 30 modules containing tens to
      hundreds of genes, whose aggregate behavior can be represented by the module's
      "eigengene." The third step is to correlate expression patterns with phenotype,
      as in GWAS, only applied to eigengenes instead of single nucleotide
      polymorphisms. The goal of the GMAS approach is to identify groups of coregulated
      genes that explain complex traits from a systems perspective. From an
      evolutionary standpoint, we hypothesize that variability in eigengene patterns
      reflects the "good enough solution" concept, that biological systems are
      sufficiently complex so that many possible combinations of the same elements (in
      this case eigengenes) can produce an equivalent output, that is, a "good enough
      solution" to accomplish normal biological functions. However, when faced with
      environmental stresses, some "good enough solutions" adapt better than others,
      explaining individual variability to disease and drug susceptibility. If
      validated, GMAS may imply that common polygenic diseases are related as much to
      group interactions between normal genes, as to multiple gene mutations.

PMID- 22859673
TI  - The rice RAD51C gene is required for the meiosis of both female and male
      gametocytes and the DNA repair of somatic cells.
AB  - The RecA/RAD51 family of rice (Oryza sativa) consists of at least 13 members.
      However, the functions of most of these members are unknown. Here the functional
      characterization of one member of this family, RAD51C, is reported. Knockout (KO)
      of RAD51C resulted in both female and male sterility in rice. Transferring RAD51C
      to the RAD51C-KO line restored fertility. Cytological analyses showed that the
      sterility of RAD51C-KO plants was associated with abnormal early meiotic
      processes in both megasporocytes and pollen mother cells (PMCs). PMCs had an
      absence of normal pachytene chromosomes and had abnormal chromosome fragments.
      The RAD51C-KO line showed no obvious difference from wild-type plants in mitosis
      in the anther wall cells, which was consistent with the observation that the
      RAD51C-KO line did not have obviously abnormal morphology during vegetative
      development. However, the RAD51C-KO line was sensitive to different DNA-damaging
      agents. These results suggest that RAD51C is essential for reproductive
      development by regulating meiosis as well as for DNA damage repair in somatic
      cells.

PMID- 22859674
TI  - PrCYP707A1, an ABA catabolic gene, is a key component of Phelipanche ramosa seed
      germination in response to the strigolactone analogue GR24.
AB  - After a conditioning period, seed dormancy in obligate root parasitic plants is
      released by a chemical stimulus secreted by the roots of host plants. Using
      Phelipanche ramosa as the model, experiments conducted in this study showed that
      seeds require a conditioning period of at least 4 d to be receptive to the
      synthetic germination stimulant GR24. A cDNA-AFLP procedure on seeds revealed 58
      transcript-derived fragments (TDFs) whose expression pattern changed upon GR24
      treatment. Among the isolated TDFs, two up-regulated sequences corresponded to an
      abscisic acid (ABA) catabolic gene, PrCYP707A1, encoding an ABA 8'-hydroxylase.
      Using the rapid amplification of cDNA ends method, two full-length cDNAs,
      PrCYP707A1 and PrCYP707A2, were isolated from seeds. Both genes were always
      expressed at low levels during conditioning during which an initial decline in
      ABA levels was recorded. GR24 application after conditioning triggered a strong
      up-regulation of PrCYP707A1 during the first 18 h, followed by an 8-fold decrease
      in ABA levels detectable 3 d after treatment. In situ hybridization experiments
      on GR24-treated seeds revealed a specific PrCYP707A1 mRNA accumulation in the
      cells located between the embryo and the micropyle. Abz-E2B, a specific inhibitor
      of CYP707A enzymes, significantly impeded seed germination, proving to be a non
      competitive antagonist of GR24 with reversible inhibitory activity. These results
      demonstrate that P. ramosa seed dormancy release relies on ABA catabolism
      mediated by the GR24-dependent activation of PrCYP707A1. In addition, in situ
      hybridization corroborates the putative location of cells receptive to the
      germination stimulants in seeds.

PMID- 22859670
TI  - Anchoring proteins as regulators of signaling pathways.
AB  - Spatial and temporal organization of signal transduction is coordinated through
      the segregation of signaling enzymes in selected cellular compartments. This
      highly evolved regulatory mechanism ensures the activation of selected enzymes
      only in the vicinity of their target proteins. In this context, cAMP-responsive
      triggering of protein kinase A is modulated by a family of scaffold proteins
      referred to as A-kinase anchoring proteins. A-kinase anchoring proteins form the
      core of multiprotein complexes and enable simultaneous but segregated cAMP
      signaling events to occur in defined cellular compartments. In this review we
      will focus on the description of A-kinase anchoring protein function in the
      regulation of cardiac physiopathology.

PMID- 22859676
TI  - Genomic asymmetry in allopolyploid plants: wheat as a model.
AB  - The evolvement of duplicated gene loci in allopolyploid plants has become the
      subject of intensive studies. Most duplicated genes remain active in
      neoallopolyploids contributing either to a favourable effect of an extra gene
      dosage or to the build-up of positive inter-genomic interactions when genes or
      regulation factors on homoeologous chromosomes are divergent. However, in a small
      number of loci (about 10%), genes of only one genome are active, while the
      homoeoalleles on the other genome(s) are either eliminated or partially or
      completely suppressed by genetic or epigenetic means. For several traits, the
      retention of controlling genes is not random, favouring one genome over the
      other(s). Such genomic asymmetry is manifested in allopolyploid wheat by the
      control of various morphological and agronomical traits, in the production of
      rRNA and storage proteins, and in interaction with pathogens. It is suggested
      that the process of cytological diploidization leading to exclusive intra-genomic
      meiotic pairing and, consequently, to complete avoidance of inter-genomic
      recombination, has two contrasting effects. Firstly, it provides a means for the
      fixation of positive heterotic inter-genomic interactions and also maintains
      genomic asymmetry resulting from loss or silencing of genes. The possible
      mechanisms and evolutionary advantages of genomic asymmetry are discussed.

PMID- 22859675
TI  - CaJOINTLESS is a MADS-box gene involved in suppression of vegetative growth in
      all shoot meristems in pepper.
AB  - In aiming to decipher the genetic control of shoot architecture in pepper
      (Capsicum spp.), the allelic late-flowering mutants E-252 and E-2537 were
      identified. These mutants exhibit multiple pleiotropic effects on the
      organization of the sympodial shoot. Genetic mapping and sequence analysis
      indicated that the mutants are disrupted at CaJOINTLESS, the orthologue of the
      MADS-box genes JOINTLESS and SVP in tomato and Arabidopsis, respectively. Late
      flowering of the primary and sympodial shoots of Cajointless indicates that the
      gene functions as a suppressor of vegetative growth in all shoot meristems. While
      CaJOINTLESS and JOINTLESS have partially conserved functions, the effect on
      flowering time and on sympodial development in pepper, as well as the epistasis
      over FASCICULATE, the homologue of the major determinant of sympodial development
      SELF-PRUNING, is stronger than in tomato. Furthermore, the solitary terminal
      flower of pepper is converted into a structure composed of flowers and leaves in
      the mutant lines. This conversion supports the hypothesis that the solitary
      flowers of pepper have a cryptic inflorescence identity that is suppressed by
      CaJOINTLESS. Formation of solitary flowers in wild-type pepper is suggested to
      result from precocious maturation of the inflorescence meristem.

PMID- 22859677
TI  - beta-Aminobutyric acid increases abscisic acid accumulation and desiccation
      tolerance and decreases water use but fails to improve grain yield in two spring
      wheat cultivars under soil drying.
AB  - A pot experiment was conducted to investigate the effect of the non-protein amino
      acid, beta-aminobutyric acid (BABA), on the homeostasis between reactive oxygen
      species (ROS) and antioxidant defence during progressive soil drying, and its
      relationship with the accumulation of abscisic acid (ABA), water use, grain
      yield, and desiccation tolerance in two spring wheat (Triticum aestivum L.)
      cultivars released in different decades and with different yields under drought.
      Drenching the soil with 100 uM BABA increased drought-induced ABA production,
      leading to a decrease in the lethal leaf water potential (Psi) used to measure
      desiccation tolerance, decreased water use, and increased water use efficiency
      for grain (WUEG) under moderate water stress. In addition, at severe water stress
      levels, drenching the soil with BABA reduced ROS production, increased
      antioxidant enzyme activity, and reduced the oxidative damage to lipid membranes.
      The data suggest that the addition of BABA triggers ABA accumulation that acts as
      a non-hydraulic root signal, thereby closing stomata, and reducing water use at
      moderate stress levels, and also reduces the production of ROS and increases the
      antioxidant defence enzymes at severe stress levels, thus increasing the
      desiccation tolerance. However, BABA treatment had no effect on grain yield of
      wheat when water availability was limited. The results suggest that there are
      ways of effectively priming the pre-existing defence pathways, in addition to
      genetic means, to improve the desiccation tolerance and WUEG of wheat.

PMID- 22859678
TI  - Cell survival after UV radiation stress in the unicellular chlorophyte Dunaliella
      tertiolecta is mediated by DNA repair and MAPK phosphorylation.
AB  - Ultraviolet radiation (UVR) induces damage in a variety of organisms, and cells
      may adapt by developing repair or tolerance mechanisms to counteract such damage;
      otherwise, the cellular fate is cell death. Here, the effect of UVR-induced cell
      damage and the associated signalling and repair mechanisms by which cells are
      able to survive was studied in Dunaliella tertiolecta. UVR did not cause cell
      death, as shown by the absence of SYTOX Green-positive labelling cells.
      Ultrastructure analysis by transmission electron microscopy demonstrated that the
      cells were alive but were subjected to morphological changes such as starch
      accumulation, chromatin disaggregation, and chloroplast degradation. This
      behaviour paralleled a decrease in F(v)/F(m) and the formation of cyclobutane
      pyrimidine dimers, showing a 10-fold increase at the end of the time course.
      There was a high accumulation of the repressor of transcriptional gene silencing
      (ROS1), as well as the cell proliferation nuclear antigen (PCNA) in UVR-treated
      cells, revealing activation of DNA repair mechanisms. The degree of
      phosphorylation of c-Jun N-terminal kinase (JNK) and p38-like mitogen-activated
      protein kinases was higher in UVR-exposed cells; however, the opposite occurred
      with the phosphorylated extracellular signal-regulated kinase (ERK). This
      confirmed that both JNK and p38 need to be phosphorylated to trigger the stress
      response, as well as the fact that cell division is arrested when an ERK is
      dephosphorylated. In parallel, both DEVDase and WEHDase caspase-like enzymatic
      activities were active even though the cells were not dead, suggesting that these
      proteases must be considered within a wider frame of stress proteins, rather than
      specifically being involved in cell death in these organisms.

PMID- 22859679
TI  - S phase of the cell cycle: a key phase for the regulation of thermodormancy in
      barley grain.
AB  - The aim of the present work was to investigate the occurrence of the cell cycle
      during germination as related to thermodormancy in barley (Hordeum vulgare L.,
      cv. Pewter) grains in relation with abscisic acid (ABA) by: (i) flow cytometry to
      determine the progression of the cell cycle; and (ii) reverse transcription-PCR
      to characterize the expression of some important genes involved in cell-cycle
      regulation. In dry embryos, cells are mostly (82%) arrested in G1 phase of the
      cell cycle, the remaining cells being in the G2 (17%) or S phase (0.9%).
      Germination at 20  degrees C was associated with an increase in the nuclei
      population in G2 and S (up to 32.5-44.5 and 9.2-11.3%, respectively, after 18
      24h). At 30  degrees C, partial reactivation of the cell cycle occurred in
      embryos of dormant grains that did not germinate. Incubation with 50mM
      hydroxyurea suggests that thermodormancy resulted in a blocking of the nuclei in
      the S phase. In dry dormant grains, transcripts of CDKA1, CYCA3, KRP4, and WEE1
      were present, while those of CDKB1, CDKD1, CYCB1, and CYCD4 were not detected.
      Incubation at 30  degrees C resulted in a strong reduction of CDKB1, CYCB1, and
      CYCD4 expression and overexpression of CDK1 and KRP4. ABA had a similar effect as
      incubation at 30  degrees C on the expression of CDKB1, CYCB1, and CYCD4, but did
      not increase that of CDK1 and KRP4. Patterns of gene expression are discussed
      with regard to thermodormancy expression and ABA.

PMID- 22859680
TI  - Identification of QTLs for eight agronomically important traits using an ultra
      high-density map based on SNPs generated from high-throughput sequencing in
      sorghum under contrasting photoperiods.
AB  - The productivity of sorghum is mainly determined by agronomically important
      traits. The genetic bases of these traits have historically been dissected and
      analysed through quantitative trait locus (QTL) mapping based on linkage maps
      with low-throughput molecular markers, which is one of the factors that hinder
      precise and complete information about the numbers and locations of the genes or
      QTLs controlling the traits. In this study, an ultra-high-density linkage map
      based on high-quality single nucleotide polymorphisms (SNPs) generated from low
      coverage sequences (~0.07 genome sequence) in a sorghum recombinant inbred line
      (RIL) population was constructed through new sequencing technology. This map
      consisted of 3418 bin markers and spanned 1591.4 cM of genome size with an
      average distance of 0.5 cM between adjacent bins. QTL analysis was performed and
      a total of 57 major QTLs were detected for eight agronomically important traits
      under two contrasting photoperiods. The phenotypic variation explained by
      individual QTLs varied from 3.40% to 33.82%. The high accuracy and quality of
      this map was evidenced by the finding that genes underlying two cloned QTLs, Dw3
      for plant height (chromosome 7) and Ma1 for flowering time (chromosome 6), were
      localized to the correct genomic regions. The close associations between two
      genomic regions on chromosomes 6 and 7 with multiple traits suggested the
      existence of pleiotropy or tight linkage. Several major QTLs for heading date,
      plant height, numbers of nodes, stem diameter, panicle neck length, and flag leaf
      width were detected consistently under both photoperiods, providing useful
      information for understanding the genetic mechanisms of the agronomically
      important traits responsible for the change of photoperiod.

PMID- 22859681
TI  - Transcriptional analysis of apple fruit proanthocyanidin biosynthesis.
AB  - Proanthocyanidins (PAs) are products of the flavonoid pathway, which also leads
      to the production of anthocyanins and flavonols. Many flavonoids have antioxidant
      properties and may have beneficial effects for human health. PAs are found in the
      seeds and fruits of many plants. In apple fruit (Malus * domestica Borkh.), the
      flavonoid biosynthetic pathway is most active in the skin, with the flavan-3-ols,
      catechin, and epicatechin acting as the initiating units for the synthesis of PA
      polymers. This study examined the genes involved in the production of PAs in
      three apple cultivars: two heritage apple cultivars, Hetlina and Devonshire
      Quarrenden, and a commercial cultivar, Royal Gala. HPLC analysis shows that tree
      ripe fruit from Hetlina and Devonshire Quarrenden had a higher phenolic content
      than Royal Gala. Epicatechin and catechin biosynthesis is under the control of
      the biosynthetic enzymes anthocyanidin reductase (ANR) and leucoanthocyanidin
      reductase (LAR1), respectively. Counter-intuitively, real-time quantitative PCR
      analysis showed that the expression levels of Royal Gala LAR1 and ANR were
      significantly higher than those of both Devonshire Quarrenden and Hetlina. This
      suggests that a compensatory feedback mechanism may be active, whereby low
      concentrations of PAs may induce higher expression of gene transcripts. Further
      investigation is required into the regulation of these key enzymes in apple.

PMID- 22859682
TI  - A rice F-box gene, OsFbx352, is involved in glucose-delayed seed germination in
      rice.
AB  - F-box proteins play diverse roles in regulating numerous physiological processes
      in plants. This study isolated a gene (OsFbx352) from rice encoding an F-box
      domain protein and characterized its role in seed germination. Expression of
      OsFbx352 was upregulated by abscisic acid (ABA). The transcripts of OsFbx352 were
      increased upon imbibition of rice seeds and the increase was markedly suppressed
      by glucose. Germination of seeds with overexpression of OsFbx352 was less
      suppressed by glucose than that of wild-type seeds, while glucose had greater
      inhibition for germination of seeds with knockdown of OsFbx352 by RNA
      interference (RNAi) than that of wild-type seeds. The differential response of
      germination of the transgenic and wild-type seeds to glucose may be accounted for
      by differences in ABA content among overexpressing, RNAi, and wild-type seeds
      such that overexpression of OsFbx352 and knockdown of OsFbx352 led to lower and
      higher ABA contents, respectively, than that of wild-type seeds in the presence
      of glucose. Overexpression of OsFbx352 led to a reduction in expression of genes
      responsible for ABA synthesis (OsNced2, OsNced3) and an increase in expression of
      genes encoding ABA catabolism (OsAba-ox2, OsAba-ox3) in the presence of glucose.
      These findings indicate that OsFbx352 plays a regulatory role in the regulation
      of glucose-induced suppression of seed germination by targeting ABA metabolism.

PMID- 22859683
TI  - Determining the absolute requirement of G protein-coupled receptor kinase 5 for
      pathological cardiac hypertrophy: short communication.
AB  - RATIONALE: Heart failure (HF) is often the end phase of maladaptive cardiac
      hypertrophy. A contributing factor is activation of a hypertrophic gene
      expression program controlled by decreased class II histone deacetylase (HDAC)
      transcriptional repression via HDAC phosphorylation. Cardiac-specific
      overexpression of G proteinen-coupled receptor kinase-5 (GRK5) has previously
      been shown to possess nuclear activity as a HDAC5 kinase, promoting an
      intolerance to in vivo ventricular pressure overload; however, its endogenous
      requirement in adaptive and maladaptive hypertrophy remains unknown. OBJECTIVE:
      We used mouse models with global or cardiomyocyte-specific GRK5 gene deletion to
      determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy and
      HF development after chronic hypertrophic stimuli. METHODS AND RESULTS: Mice with
      global deletion of GRK5 were subjected to transverse aortic constriction. At 12
      weeks, these mice showed attenuated hypertrophy, remodeling, and hypertrophic
      gene transcription along with preserved cardiac function. Global GRK5 deletion
      also diminished hypertrophy and related gene expression due to chronic
      phenylephrine infusion. We then generated mice with conditional, cardiac-specific
      deletion of GRK5 that also demonstrated similar protection from pathological
      cardiac hypertrophy and HF after transverse aortic constriction. CONCLUSIONS:
      These results define myocyte GRK5 as a critical regulator of pathological cardiac
      growth after ventricular pressure overload, supporting its role as an endogenous
      (patho)-physiological HDAC kinase. Further, these results define GRK5 as a
      potential therapeutic target to limit HF development after hypertrophic stress.

PMID- 22859685
TI  - The estrogen puzzle in pulmonary arterial hypertension.

PMID- 22859684
TI  - Activity of the estrogen-metabolizing enzyme cytochrome P450 1B1 influences the
      development of pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a hyperproliferative
      vascular disorder observed predominantly in women. Estrogen is a potent mitogen
      in human pulmonary artery smooth muscle cells and contributes to PAH in vivo;
      however, the mechanisms attributed to this causation remain obscure. Curiously,
      heightened expression of the estrogen-metabolizing enzyme cytochrome P450 1B1
      (CYP1B1) is reported in idiopathic PAH and murine models of PAH. METHODS AND
      RESULTS: Here, we investigated the putative pathogenic role of CYP1B1 in PAH.
      Quantitative reverse transcription-polymerase chain reaction, immunoblotting, and
      in situ analysis revealed that pulmonary CYP1B1 is increased in hypoxic PAH,
      hypoxic+SU5416 PAH, and human PAH and is highly expressed within the pulmonary
      vascular wall. PAH was assessed in mice via measurement of right ventricular
      hypertrophy, pulmonary vascular remodeling, and right ventricular systolic
      pressure. Hypoxic PAH was attenuated in CYP1B1(-/-) mice, and the potent CYP1B1
      inhibitor 2,3',4,5'-tetramethoxystilbene (TMS; 3 mg . kg(-1) . d(-1) IP)
      significantly attenuated hypoxic PAH and hypoxic+SU5416 PAH in vivo. TMS also
      abolished estrogen-induced proliferation in human pulmonary artery smooth muscle
      cells and PAH-pulmonary artery smooth muscle cells. The estrogen metabolite
      16alpha-hydroxyestrone provoked human pulmonary artery smooth muscle cell
      proliferation, and this mitogenic effect was greatly pronounced in PAH-pulmonary
      artery smooth muscle cells. ELISA analysis revealed that 16alpha-hydroxyestrone
      concentration was elevated in PAH, consistent with CYP1B1 overexpression and
      activity. Finally, administration of the CYP1B1 metabolite 16alpha-hydroxyestrone
      (1.5 mg . kg(-1) . d(-1) IP) caused the development of PAH in mice. CONCLUSIONS:
      Increased CYP1B1-mediated estrogen metabolism promotes the development of PAH,
      likely via the formation of mitogens, including 16alpha-hydroxyestrone.
      Collectively, this study reveals a possible novel therapeutic target in clinical
      PAH.

PMID- 22859686
TI  - Echo rounds: transesophageal echocardiography findings associated with
      transvenous lead extraction.

PMID- 22859687
TI  - En face view of the mitral valve: definition and acquisition.
AB  - A 3-dimensional echocardiographic view of the mitral valve, called the "en face"
      or "surgical view," presents a view of the mitral valve similar to that seen by
      the surgeon from a left atrial perspective. Although the anatomical landmarks of
      this view are well defined, no comprehensive echocardiographic definition has
      been presented. After reviewing the literature, we provide a definition of the
      left atrial and left ventricular en face views of the mitral valve. Techniques
      used to acquire this view are also discussed.

PMID- 22859688
TI  - Deficits in the provision of cardiopulmonary resuscitation during simulated
      obstetric crises: results from the Israeli Board of Anesthesiologists.
AB  - BACKGROUND: Cardiac arrest in the parturient is often fatal, but appropriate
      resuscitation in this special situation may save the lives of the mother and/or
      unborn baby. Concern has arisen as to application of recommended techniques for
      resuscitation in the obstetric patient. The Israel Board of Anesthesiology has
      incorporated simulation assessment into accreditation examinations. The
      candidates represent a unique national cohort in which we were able to assess
      competence in the simulated scenario of cardiorespiratory arrest in the
      parturient.  METHODS A simulated scenario of preeclampsia with magnesium toxicity
      leading to cardiac arrest in a pregnant patient was performed by 25 senior
      anesthesiology residents. A unique two-stage simulation examination consisting of
      high fidelity simulation followed immediately by oral debriefing was conducted.
      The assessment was scored using a predetermined checklist of key actions and
      answers to clarifying questions. Simulation performance was compared to
      debriefing performance.  RESULTS During the board examination, resuscitation not
      specific to the pregnant patient was performed well (commencing chest
      compressions, bag-mask ventilation, cardiac defibrillation); however actions
      specific to the parturient were performed poorly. Left uterine displacement,
      cricoid pressure during bag-mask ventilation, and instructing preparations to be
      made for perimortem cesarean delivery within 5 minutes were performed by 68%,
      48%, and 40% of candidates respectively (lower 99% confidence limit 42%, 25%, and
      19%, respectively). Cricoid pressure during bag-mask ventilation was performed by
      48% (25%) but described in debriefing by 80% of candidates (53%) (P = 0.08), and
      time setting for perimortem cesarean delivery was performed by 40% (29%) but
      described by 80% (53%) (P = 0.05) of examinees.  CONCLUSIONS Senior
      anesthesiology residents have poor knowledge of resuscitation of the pregnant
      patient. The results suggest 2-stage simulation including an oral component may
      reveal disparities in knowledge not assessed by simulation alone, but definitive
      conclusions require further study.

PMID- 22859689
TI  - General anesthesia: a gateway to modulate synapse formation and neural
      plasticity?
AB  - Appropriate balance between excitatory and inhibitory neural activity patterns is
      of utmost importance in the maintenance of neuronal homeostasis. General
      anesthetic-induced pharmacological interference with this equilibrium results not
      only in a temporary loss of consciousness but can also initiate long-term changes
      in brain function. Although these alterations were initially considered
      deleterious, recent observations suggest that at least under some specific
      conditions, they may eventually improve neural function. The goal of this review
      is to provide insights into the mechanisms underlying these dual effects. Basic
      science issues on the important role of critical periods during neural circuitry
      assembly will be discussed to better understand how even brief exposures to
      general anesthetics could initiate context-dependent lasting changes in neuronal
      structure and function. Recent series of observations suggesting a developmental
      stage-dependent impact of these drugs on synaptogenesis will then be summarized
      together with currently known molecular mechanisms underlying these effects.
      Particular emphasis will be placed on how anesthetic drugs modulate neural
      plasticity in the adult brain and how this may improve neural function under some
      pathological states. The ensemble of these new observations strongly suggests
      that general anesthetics should not merely be considered toxic drugs but rather
      acknowledged as robust, context-dependent modulators of neural plasticity.

PMID- 22859690
TI  - A case series of recombinant platelet factor 4 for heparin reversal after
      cardiopulmonary bypass.
AB  - BACKGROUND: Platelet factor 4 (PF4) is released by activated platelets and has a
      strong affinity for heparin. Recombinant PF4 (rPF4) has been previously
      considered as an alternative to protamine for heparin reversal. However, it has
      been demonstrated that antibodies directed against the PF4/heparin moiety are
      important in the pathophysiologic development of heparin-induced
      thrombocytopenia, a prothrombotic complication for which cardiac bypass patients
      are at increased risk. METHODS: We retrospectively analyzed a case series from an
      open-label, comparative phase I-II study of rPF4 and protamine after cardiac
      surgery to determine the heparin-reversal activity of different doses of IV rPF4.
      Sixteen patients received rPF4, and 5 received protamine. Activated clotting time
      (ACT) was used to monitor heparin reversal, with reversal defined as ACT <150
      seconds. Platelets, white blood cells, C3a, C5a, fibrinopeptide A, von Willebrand
      factor antigen, and prothrombin fragment 1.2 were monitored postoperatively as
      indicators of coagulation and inflammation. RESULTS: Heparin reversal was
      successful by 10 minutes after administration of rPF4 as measured by ACT in all
      16 patients. Specifically, a dose of 5 mg/kg rPF4 resulted in ACT <150 seconds
      after 5 minutes in 10 of 10 patients. For both treatment groups, there were no
      bleeding or thrombotic complications, no clinical thrombocytopenia after day 5,
      and no deaths within the 30-day study period. CONCLUSIONS: Our case series
      demonstrates that heparin anticoagulation was effectively reversed by the
      administration of rPF4 without serious complications. Additional studies are
      needed to further validate the safety and efficacy of exogenous rPF4
      administration.

PMID- 22859691
TI  - Case report: an unforeseen peril of parental presence during induction of
      anesthesia.
AB  - Parental presence during induction of anesthesia is a common practice to allay
      perioperative anxiety in the pediatric population. We present the first
      documented case in the anesthesia literature of parental interruption of
      induction of anesthesia. The report is to inform practitioners of the need for
      perioperative screening, education, and contingency planning to prepare for the
      possibility of familial disruption during pediatric inductions, cesarean
      deliveries, and other practice settings that may have lay people present.

PMID- 22859692
TI  - Special article: T. H. Seldon (1905-1991).
AB  - Dr. Seldon was Editor of Anesthesia & Analgesia from 1954 to 1977. We examined
      how he led the effort to transform this journal into a clinically relevant and
      vital publication for the specialty.

PMID- 22859693
TI  - Childhood ataxia: clinical features, pathogenesis, key unanswered questions, and
      future directions.
AB  - Childhood ataxia is characterized by impaired balance and coordination primarily
      because of cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia,
      is the most common multisystem autosomal recessive disease. Most of these
      patients are homozygous for the GAA repeat expansion located on the first intron
      of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair
      mitochondrial function, increase reactive oxygen species, and trigger
      redistribution of iron in the mitochondria and cytosol. Targeted therapies for
      Friedreich ataxia are undergoing testing. In addition, a centralized database,
      patient registry, and natural history study have been launched to support
      clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in
      Children symposium, held in conjunction with the 40th annual Child Neurology
      Society meeting, aimed to (1) describe clinical features surrounding Friedreich
      ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the
      understanding of the pathogenesis of Friedreich ataxia and developments of
      clinical trials; (3) review new investigations of characteristic symptoms; and
      (4) establish clinical and biochemical overlaps in neurodegenerative diseases and
      possible directions for future basic, translational, and clinical studies.

PMID- 22859694
TI  - Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome: a case report.
AB  - This report describes a case of megalencephaly-polymicrogyria-polydactyly
      hydrocephalus syndrome in a 1-year-old boy, born to healthy nonconsanguineous
      parents. Megalencephaly and bilateral postaxial polydactyly of upper and lower
      limbs were noted at birth. He had profound developmental delay and moderate
      hypotonia. Magnetic resonance imaging (MRI) of the brain revealed hydrocephalus,
      polymicrogyria in both frontal lobes and perisylvian regions, and thin corpus
      callosum. Array-comparative genomic hybridization was normal. The patient's
      clinical and radiologic findings fit the classic description of megalencephaly
      polymicrogyria-polydactyly-hydrocephalus syndrome. The possible overlap between
      megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome and other
      similar conditions is discussed.

PMID- 22859695
TI  - Case series: fractional anisotropy along the trajectory of selected white matter
      tracts in adolescents born preterm with ventricular dilation.
AB  - This case series assesses white matter microstructure in 3 adolescents born
      preterm with nonshunted ventricular dilation secondary to intraventricular
      hemorrhage. Subjects (ages 12-17 years, gestational age 26-29 weeks, birth weight
      825-1624 g) were compared to 3 full-term controls (13-17 years, 39-40 weeks, 3147
      3345 g) and 3 adolescents born preterm without ventricular dilation (10-13 years,
      26-29 weeks, 630-1673 g). Tractography using a 2 region of interest method
      reconstructed the following white matter tracts: superior longitudinal/arcuate
      fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital
      fasciculus, uncinate fasciculus, and corticospinal tract. Subjects showed
      increased fractional anisotropy and changes in the pattern of fractional
      anisotropy along the trajectory of tracts adjacent to the lateral ventricles.
      Tensor shape at areas of increased fractional anisotropy demonstrated increased
      linear anisotropy at the expense of planar and spherical anisotropy. These
      findings suggest increased axonal packing density and straightening of fibers
      secondary to ventricular enlargement.

PMID- 22859696
TI  - Increased frontomotor oscillations during tic suppression in children with
      Tourette syndrome.
AB  - This work investigated whether Tourette syndrome patients exhibit alterations in
      neural oscillations during spontaneous expression and suppression of tics.
      Electroencephalograms (EEGs) were recorded from 9 medication-naive children with
      Tourette syndrome and 10 age-matched healthy subjects in resting conditions and
      during tic suppression. Their cortical oscillations were examined using the power
      spectral method and partial directed coherence. The authors found increased
      oscillations of broad frequency bands in the frontomotor regions of patients
      during tic expression, suggesting the involvement of aberrant cortical
      oscillations in Tourette syndrome. More significantly, prominent increases in
      theta oscillation in the prefrontal area and directed frontomotor interactions in
      the theta and beta bands were observed during tic suppression. Furthermore, the
      directed EEG interaction from the frontal to motor regions was positively
      correlated with the severity of tic symptoms. These findings suggest that the
      frontal to motor interaction of cortical oscillations plays a significant role in
      tic suppression.

PMID- 22859697
TI  - The spectrum of neuromyelitis optica (NMO) in childhood.
AB  - The evaluation of inflammatory central nervous system disorders in childhood with
      predominant involvement of the optic nerves and spinal cord has been greatly
      enhanced over the last decade with identification of a group of disorders unified
      by the detection of neuromyelitis optica (NMO)-IgG, an antibody targeting the
      central nervous system-predominant water channel aquaporin-4. Clinical syndromes
      are predominated by the relapsing form of NMO but also include encephalopathic
      variants that can mimic acute disseminated encephalomyelitis. Maintenance
      immunotherapy is used to prevent relapses in NMO-IgG-seropositive patients. In
      contrast, NMO-IgG-seronegative children with NMO more commonly have a monophasic
      course (simultaneous occurrence of optic neuritis and transverse myelitis) and do
      not require remission-maintaining immunotherapy, but close surveillance is
      advised. Current clinical, pathological, and pathogenetic knowledge is reviewed
      with a focus on clinical presentation, neuroimaging findings, serological
      investigations, and treatment of children with disorders within the spectrum of
      central nervous system aquaporin-4 autoimmunity.

PMID- 22859698
TI  - Language differences between monolingual English and bilingual English-Spanish
      young children with autism spectrum disorders.
AB  - Bilingualism is common worldwide and increasingly prevalent, but there is little
      information about bilingual children with autism spectrum disorder. The goal of
      the study was to compare expressive and receptive language skills in monolingual
      English and bilingual English-Spanish children with autism spectrum disorder. A
      review of the multidisciplinary evaluations done in toddlers who were diagnosed
      with autism spectrum disorder at a university-affiliated center between 2003 and
      2010 was performed. Data included demographics, developmental testing, autistic
      characteristics, and expressive and receptive language skills, obtained from
      formal speech and language evaluation. A total of 80 toddlers were identified, 40
      classified as bilingual English-Spanish. Compared with monolinguals, bilingual
      children were more likely to vocalize and utilize gestures, with no other
      differences in language skills. There were no differences in cognitive
      functioning and autistic features between the groups. In this study, bilingualism
      did not negatively affect language development in young children with autism
      spectrum disorder.

PMID- 22859699
TI  - Corticosteroids for the treatment of infantile spasms: a systematic review.
AB  - Adrenocorticotropic hormone (ACTH) and corticosteroids are the usual first-line
      treatment options for infantile spasms. Despite significant differences, these
      agents are often lumped together in this context. There is a need to
      systematically explore the efficacy of corticosteroids in the treatment of
      infantile spasms, especially in comparison to ACTH. This review identified and
      analyzed corticosteroid clinical trials and summarized their short-term efficacy
      and tolerability. Primary outcome was cessation of spasms and abolition of
      hypsarrhythmia on prolonged video electroencephalographic monitoring. Eight
      corticosteroid clinical trials were found with only 2 fulfilling the criteria for
      adequate design. The weighted-mean efficacy of corticosteroids to achieve primary
      outcome was 31% for these 2 methodologically adequate studies. Including
      reanalyzed data from 3 other studies, the corticosteroid efficacy was found to be
      42%. On the basis of the available evidence, the efficacy of high-dose
      corticosteroids is similar to low-dose ACTH and inferior to high-dose ACTH, the
      current standard treatment.

PMID- 22859700
TI  - Precursors of executive function in infants with sickle cell anemia.
AB  - Executive dysfunction occurs in sickle cell anemia, but there are few early data.
      Infants with sickle cell anemia (n = 14) and controls (n = 14) performed the "A
      not-B" and Object Retrieval search tasks, measuring precursors of executive
      function at 9 and 12 months. Significant group differences were not found.
      However, for the A-not-B task, 7 of 11 sickle cell anemia infants scored in the
      lower 2 performance categories at 9 months, but only 1 at 12 months (P = .024);
      controls obtained scores at 12 months that were statistically comparable to the
      scores they had already obtained at 9 months. On the Object Retrieval task, 9-
      and 12-month controls showed comparable scores, whereas infants with sickle cell
      anemia continued to improve (P = .027); at 9 months, those with lower hemoglobin
      oxygen saturation passed fewer trials (R s = 0.670, P = .024) and took longer to
      obtain the toy (R s = -0.664, P = .013). Subtle delays in acquiring developmental
      skills may underlie abnormal executive function in childhood. 

PMID- 22859701
TI  - Components of depression in Parkinson disease.
AB  - Depression is a clinically heterogeneous disorder common in Parkinson disease
      (PD). The goal of this study was to characterize PD depression in terms of
      components, including negative affect, apathy, and anhedonia. Ninety-five,
      nondemented individuals with idiopathic PD underwent a diagnostic interview and
      psychological battery. Twenty-seven patients (28%) met Diagnostic and Statistical
      Manual of Mental Disorders (Fourth Edition [DSM-IV]) criteria for a current
      depressive episode. The best-fitting confirmatory factor analysis model had 3
      factors (negative affect, apathy, and anhedonia). Apathy loaded most strongly
      onto a second-order factor representing global psychological disturbance. All
      factors are uniquely associated with depression status. Negative affect exhibited
      the strongest relationship. Psychological disturbance in PD is heterogeneous and
      can produce symptoms of apathy, anhedonia, and negative affect. Apathy appears to
      be the core neuropsychiatric feature of PD, whereas negative affect (eg,
      dysphoria) seems to be most pathognomonic of depression. Future studies should
      examine the specific neural correlates and treatment response patterns unique to
      these 3 components.

PMID- 22859702
TI  - Montreal Cognitive Assessment (MoCA): validation study for frontotemporal
      dementia.
AB  - The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the
      screening of milder forms of cognitive impairment, having surpassed the well
      known limitations of the Mini-Mental State Examination (MMSE). The aim of the
      present study was to validate the MoCA as a cognitive screening test for
      behavioral-variant frontotemporal dementia (bv-FTD) by examining its psychometric
      properties and diagnostic accuracy. Three matched subgroups of participants were
      considered: bv-FTD (n = 50), Alzheimer disease (n = 50), and a control group of
      healthy adults (n = 50). Compared with the MMSE, the MoCA demonstrated
      consistently superior psychometric properties and discriminant capacity,
      providing comprehensive information about the patients' cognitive profiles. The
      diagnostic accuracy of MoCA for bv-FTD was extremely high (area under the curve
      AUC [MoCA] = 0.934, 95% confidence interval [CI] = 0.866-.974; AUC [MMSE] =
      0.772, 95% CI = 0.677-0.850). With a cutoff below 17 points, the MoCA results for
      sensitivity, specificity, positive predictive value, negative predictive value,
      and classification accuracy were significantly superior to those of the MMSE. The
      MoCA is a sensitive and accurate instrument for screening the patients with bv
      FTD and represents a better option than the MMSE.

PMID- 22859703
TI  - The rates of postmortem proteolysis of glutamate transporters differ dramatically
      between cells and between transporter subtypes.
AB  - Glutamate transporters (GLT-1, GLAST, EAAC1) limit the actions of excitatory
      amino acids. Because a disturbed transporter operation can cause or aggravate
      neurological diseases, transporters are of considerable neuropathological
      interest. Human samples, however, are seldom obtained fresh. Here, we used mice
      brains to study how fast glutamate transporters are degraded after death.
      Immunoblots showed that terminal GLT-1 epitopes (within residues 1-26 and 518
      573) had mostly disappeared after 24 hr. GLAST termini (1-25 and 522-543)
      degraded slightly slower. In contrast, epitopes within central parts of GLT-1
      (493-508) and the EAAC1 C-terminus (510-523) were readily detectable after 72 hr.
      The decline in immunoreactivity of the GLT-1 and GLAST termini was also seen in
      tissue sections, but proteolysis did not happen synchronously in all cells. At 24
      hr, scattered cells remained strongly immunopositive, while the majority of cells
      were completely immunonegative. GLAST and GLT-1 co-localized in neocortical
      tissue, but at 12 hr, many GLAST-positive cells had lost the GLT-1 termini. The
      uneven disappearance of labeling was not observed with the antibodies to GLT-1
      residues 493-508. The immunoreactivity to this epitope correlated better with the
      reported glutamate uptake activity. Thus, postmortem delay may affect epitopes
      differently, possibly causing erroneous conclusions about relative expression
      levels.

PMID- 22859704
TI  - BrdU birth dating can produce errors in cell fate specification in chick brain
      development.
AB  - Birth dating neurons with bromodeoxyuridine (BrdU) labeling is an established
      method widely employed by neurobiologists to study cell proliferation in
      embryonic, postnatal, and adult brain. Birth dating studies in the chick dorsal
      telencephalon and the mammalian striatum have suggested that these structures
      develop in a strikingly similar manner, in which neurons with the same birth date
      aggregate to form "isochronic clusters." Here we show that isochronic cluster
      formation in the chick dorsal telencephalon is an artifact. In embryos given
      standardly employed doses of BrdU, we observed isochronic clusters but found that
      clusters were absent with BrdU doses close to the limits of detection. In
      addition, in situ hybridization experiments established that neurons in the
      clusters display errors in cell type specification: BrdU cell clusters in
      nidopallium adopted a mesopallial neuronal fate, mesopallial clusters were
      misspecified as nidopallial cells, and in some instances, the BrdU clusters
      failed to express neuronal differentiation markers characteristic of the dorsal
      telencephalon. These results demonstrate that the chick dorsal telencephalon does
      not develop by isochronic cluster formation and highlight the need to test the
      integrity of BrdU-treated tissue with gene expression markers of regional and
      cell type identity.

PMID- 22859705
TI  - Hypertrophic chondrocytes have a limited capacity to cope with increases in
      endoplasmic reticulum stress without triggering the unfolded protein response.
AB  - Mutations causing metaphyseal chondrodysplasia type Schmid (MCDS) (e.g.,
      Col10a1p.N617K) induce the pathology by a mechanism involving increased
      endoplasmic reticulum (ER) stress triggering an unfolded protein response (UPR)
      in hypertrophic chondrocytes (Rajpar et al. 2009). Here we correlate the
      expression of mutant protein with the onset of the UPR and disease pathology
      (hypertrophic zone [HZ] expansion) in MCDS and ColXTg(cog) mouse lines from E14.5
      to E17.5. Embryos homozygous for the Col10a1p.N617K mutation displayed a delayed
      secretion of mutant collagen X accompanied by a UPR at E14.5, delayed
      ossification of the primary center at E15.5, and an expanded HZ at E17.5.
      Heterozygote embryos expressed mutant collagen X from E14.5 but exhibited no
      evidence of a UPR or an HZ expansion until after E17.5. Embryos positive for the
      ER stress-inducing ColXTg(cog) allele expressed Tg(cog) at E14.5, but the onset
      of the UPR was not apparent until E15.5 in homozygous and E17.5 in hemizygous
      embryos. Only homozygous embryos exhibited an HZ expansion at E17.5. The
      differential onset of the UPR and pathology, dependent on mutation type and gene
      dosage, indicates that hypertrophic chondrocytes have a latent capacity to deal
      with ER stress, which must be exceeded to trigger the UPR and HZ expansion.

PMID- 22859706
TI  - Hepatocyte growth factor enhances alternative splicing of the Kruppel-like factor
      6 (KLF6) tumor suppressor to promote growth through SRSF1.
AB  - Alternative splicing of the Kruppel-like factor 6 (KLF6) tumor suppressor into an
      antagonistic splice variant 1 (SV1) is a pathogenic event in several cancers
      including hepatocellular carcinoma (HCC) because elevated SV1 is associated with
      increased tumor metastasis and mortality. Ras activation is one factor that can
      enhance KLF6 splicing in cancer cells, however pathways driving KLF6 splicing are
      unknown. Splice site selection is regulated by splice factors that include
      serine/arginine-rich (SR) proteins such as SRSF1 (ASF-SF2), which in turn is
      controlled by phosphoinositide 3-kinase (PI3K)/Akt and the mitogen-activated
      protein kinase (MAPK) signaling pathway. Because signaling pathways downstream of
      the liver mitogen hepatocyte growth factor (HGF) include Akt, we explored whether
      HGF induces KLF6 alternative splicing. In HepG2 cells, HGF (25 ng/mL)
      significantly increases the ratio of SV1/KLF6 full by 40% through phosphorylation
      of Akt and subsequent downregulation of two splicing regulators, SRSF3 (SRp20)
      and SRSF1. Decreased SRSF3 levels regulate SRSF1 levels by alternative splicing
      associated with the nonsense-mediated mRNA decay pathway (AS-NMD), which
      stimulates cell growth by decreasing p21 levels. Enhanced cell replication
      through increased KLF6 alternative splicing is a novel growth-promoting pathway
      of HGF that could contribute to the molecule's mitogenic activity in physiologic
      liver growth and hepatocellular carcinoma.

PMID- 22859708
TI  - Darwinian evolution and tiding clones in multiple myeloma.
AB  - In this issue of Blood, Keats et al,(1) Egan et al,(2) and Walker et al(3)
      provide a genome-wide snapshot of the clonal landscape in multiple
      myeloma(MM)illustrating the complexity of the evolutionary process and the
      dynamics of clonal evolution over time.

PMID- 22859707
TI  - Inhibition of the hedgehog pathway targets the tumor-associated stroma in
      pancreatic cancer.
AB  - PURPOSE: The Hedgehog (Hh) pathway has emerged as an important pathway in
      multiple tumor types and is thought to be dependent on a paracrine signaling
      mechanism. The purpose of this study was to determine the role of pancreatic
      cancer-associated fibroblasts (human pancreatic stellate cells, HPSCs) in Hh
      signaling. In addition, we evaluated the efficacy of a novel Hh antagonist,
      AZD8542, on tumor progression with an emphasis on the role of the stroma
      compartment. EXPERIMENTAL DESIGN: Expression of Hh pathway members and activation
      of the Hh pathway were analyzed in both HPSCs and pancreatic cancer cells. We
      tested the effects of Smoothened (SMO) inhibition with AZD8542 on tumor growth in
      vivo using an orthotopic model of pancreatic cancer containing varying amounts of
      stroma. RESULTS: HPSCs expressed high levels of SMO receptor and low levels of Hh
      ligands, whereas cancer cells showed the converse expression pattern. HPSC
      proliferation was stimulated by Sonic Hedgehog with upregulation of downstream
      GLI1 mRNA. These effects were abrogated by AZD8542 treatment. In an orthotopic
      model of pancreatic cancer, AZD8542 inhibited tumor growth only when HPSCs were
      present, implicating a paracrine signaling mechanism dependent on stroma. Further
      evidence of paracrine signaling of the Hh pathway in prostate and colon cancer
      models is provided, demonstrating the broader applicability of our findings.
      CONCLUSION: Based on the use of our novel human-derived pancreatic cancer
      stellate cells, our results suggest that Hh-targeted therapies primarily affect
      the tumor-associated stroma, rather than the epithelial compartment.

PMID- 22859709
TI  - Iron out for nontransfused thalassemia.
AB  - Individuals with beta-thalassemia intermedia and hemoglobinopathies of equivalent
      severity who are infrequently or never transfused can still develop serious
      complications of iron overload. Taher et al report the first 1-year, randomized,
      double-blind, placebo-controlled trial of oral iron chelation therapy with
      deferasirox in this population.

PMID- 22859710
TI  - HIT-antibodies promote their own antigen.
AB  - Antiplatelet factor 4 (PF4) antibodies have an important role in the most
      frequent drug-induced immune disorder, heparin-induced thrombocytopenia (HIT). In
      this issue of Blood, Sachais and coworkers propose a new feature that may explain
      why only some anti-PF4 antibodies are pathogenic.(1) In addition to epitope
      specificity-determining affinity and a high titer, the ability of antibodies to
      promote formation of their own target antigens seems to be a key factor for
      pathogenicity.

PMID- 22859711
TI  - Across racial/ethnic boundaries: investigating intimate violence within a
      national sample.
AB  - The number of interracial relationships in the United States continues to
      increase. The fact is, though, that race remains a significant influence in the
      lives of individuals and in their relationships. Although there is evidence that
      relationships that cross racial/ethnic boundaries may be at greater risk for
      conflict and dissolution, there have been few investigations as to whether such
      relationships are at greater risk for violence. Using data from the National
      Violence Against Women Survey, I find that there are differences in risk of
      intimate violence depending on the racial/ethnic dyad of the couple. Ethnic
      monoracial relationships demonstrate the greatest risk for physical and
      nonphysical forms of violence, controlling for structural factors, whereas women
      in interracial relationships report higher rates of nonphysical violence, as
      compared with women in White monoracial relationships. Implications for theory
      and practice are discussed.

PMID- 22859712
TI  - Blood pressure and plasma renin activity responses to different strategies to
      inhibit the renin-angiotensin-aldosterone system during exercise.
AB  - OBJECTIVE: The effect of two different strategies for renin-angiotensin
      aldosterone system (RAAS) blockade; direct renin inhibition (DRI) versus
      angiotensin receptor blockade (ARB) on blood pressure (BP) and plasma renin
      activity (PRA) was compared during exercise. METHODS: Hypertensive adults were
      randomised to aliskiren (300 mg once daily, n=33) or valsartan (320 mg once
      daily, n=35). BP and PRA were measured during treadmill exercise (Bruce
      protocol), at baseline, end of treatment (eight weeks), and after treatment
      withdrawal (48 hours after last dose). RESULTS: After eight weeks treatment,
      Aliskiren inhibited PRA (>80%) at rest and during exercise, with inhibition
      remaining undiminished 48 hours after treatment withdrawal. In contrast,
      valsartan increased PRA at rest, and more-so during exercise (>400%). Angiotensin
      receptor blockade, as indicated by PRA increase, was reduced, 48 hours after
      valsartan treatment withdrawal, suggesting more sustained RAAS blockade with
      aliskiren. Despite divergent effects on PRA, similar exercise-induced changes in
      BP were seen. The primary outcome, the rise in systolic BP from rest to peak
      exercise (baseline to after treatment withdrawal) did not differ between
      treatments (p=0.25). CONCLUSION: Measurement of PRA is a more sensitive index of
      RAAS blockade than the BP response during exercise. Furthermore, after treatment
      withdrawal, aliskiren provides more sustained RAAS inhibition than valsartan at
      rest and during exercise.

PMID- 22859713
TI  - Angiotensin II receptor blockade reduces salt sensitivity of blood pressure
      through restoration of renal nitric oxide synthesis in patients with diabetic
      nephropathy.
AB  - INTRODUCTION: We have previously demonstrated the increased salt sensitivity of
      blood pressure (BP) in diabetic patients with early nephropathy. Here, we
      examined the effects of an angiotensin II receptor blocker (ARB) on salt
      sensitivity and renal oxidative stress or nitric oxide (NO) in those patients.
      PATIENTS AND METHODS: Type 2 diabetic patients with (n = 6) and without (n = 6)
      microalbuminuria were studied on a high-salt diet for one week and on a salt
      restricted diet for one week. The study was repeated in the patients with
      microalbuminuria during treatment with an ARB, valsartan (80 mg/day). Salt
      sensitivity was assessed from the BP/sodium excretion curve. Urinary excretion
      rates of NOx, 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress, and
      plasma tetrahydrobiopterin as a cofactor for NO synthase were measured. RESULTS:
      Compared with diabetic patients without microalbuminuria, patients with
      microalbuminuria showed greater salt sensitivity and lower urinary excretion of
      NOx. In the patients with microalbuminuria, treatment with valsartan reduced salt
      sensitivity in association with increased NOx excretion, reduced 8-hydroxy-2,
      deoxyguanosine excretion, and increased plasma tetrahydrobiopterin levels.
      CONCLUSIONS: These data support the hypothesis that ARBs reduce the salt
      sensitivity of BP by decreasing renal oxidative stress and restoring NO activity
      in diabetic patients with microalbuminuria.

PMID- 22859714
TI  - Ordinal preference elicitation methods in health economics and health services
      research: using discrete choice experiments and ranking methods.
AB  - INTRODUCTION: The predominant method of economic evaluation is cost-utility
      analysis, which uses cardinal preference elicitation methods, including the
      standard gamble and time trade-off. However, such approach is not suitable for
      understanding trade-offs between process attributes, non-health outcomes and
      health outcomes to evaluate current practices, develop new programmes and predict
      demand for services and products. Ordinal preference elicitation methods
      including discrete choice experiments and ranking methods are therefore commonly
      used in health economics and health service research. AREAS OF AGREEMENT:
      Cardinal methods have been criticized on the grounds of cognitive complexity,
      difficulty of administration, contamination by risk and preference attitudes, and
      potential violation of underlying assumptions. Ordinal methods have gained
      popularity because of reduced cognitive burden, lower degree of abstract
      reasoning, reduced measurement error, ease of administration and ability to use
      both health and non-health outcomes. AREAS OF CONTROVERSY: The underlying
      assumptions of ordinal methods may be violated when respondents use cognitive
      shortcuts, or cannot comprehend the ordinal task or interpret attributes and
      levels, or use 'irrational' choice behaviour or refuse to trade-off certain
      attributes. CURRENT USE AND GROWING AREAS: Ordinal methods are commonly used to
      evaluate preference for attributes of health services, products, practices,
      interventions, policies and, more recently, to estimate utility weights. AREAS
      FOR ON-GOING RESEARCH: There is growing research on developing optimal designs,
      evaluating the rationalization process, using qualitative tools for developing
      ordinal methods, evaluating consistency with utility theory, appropriate
      statistical methods for analysis, generalizability of results and comparing
      ordinal methods against each other and with cardinal measures.

PMID- 22859715
TI  - Varicella vaccines.
AB  - BACKGROUND: Varicella zoster virus infection (VZV) is widespread and clinically
      important as the cause of varicella pneumonitis and meningoencephalitis (a
      complication of primary infection/zoster) and post-herpetic neuralgia (a
      complication of zoster/secondary infection). The use of live-attenuated varicella
      vaccine to reduce the burden of these diseases has been established in many
      countries for a number of years. SOURCES OF DATA: Original papers and review
      articles including guidelines and recommendations by the American Academy of
      Paediatrics Committee on Infectious Diseases, the Advisory Committee on
      Immunization Practices and EuroSurveillance. AREAS OF AGREEMENT: Immunoassay of
      VZV IgG by enzyme immunosorbent assay is used as a surrogate marker for previous
      primary infection or successful immunization. Patients who have had natural
      primary infection do not require vaccination against varicella. Live VZV vaccines
      are safe and effective at protecting against disease caused by VZV. To ensure
      long-term protection, a two-dose immunization regime is strongly recommended, due
      to significant waning of protection following a single dose. Universal two-dose
      immunization has been shown to be cost-effective in Western temperate countries.
      In many countries, routine vaccination of children is recommended but, due to
      cost, often not provided by universal programmes. Cost-effectiveness of a
      universal programme will be determined by the baseline rate of severe varicella
      disease. AREAS OF CONTROVERSY: No international consensus exists: measurement of
      VZV immunity or cost-effectiveness of introducing VZV vaccination to a country.
      Decisive factors will include the pre-vaccination burden of VZV-associated
      disease.

PMID- 22859716
TI  - Zeroing in on ROS1 rearrangements in non-small cell lung cancer.
AB  - Rimkunas and colleagues report on the development and validation of an
      immunohistochemical assay evaluating non-small cell lung cancers (NSCLC) for the
      presence of ROS1 fusions. The diagnostic was validated in a screen of 556 NSCLCs,
      identifying 9 (1.6%) tumors with oncogenic ROS1 rearrangements. These patients
      are candidates for ROS1-targeted therapies.

PMID- 22859717
TI  - Might cigarettes be a "smoking gun" to reduce taxane myelotoxicity?
AB  - de Graan and colleagues report a retrospective study of the effects of cigarette
      smoking on taxane pharmacokinetics and myelosuppression. There was no difference
      in taxane pharmacokinetic clearance between smokers and nonsmokers. Further
      prospective studies of the effects of cigarette smoking on myelosuppression would
      be of interest.

PMID- 22859718
TI  - Biomarkers in hepatocellular carcinoma--letter.

PMID- 22859719
TI  - Chemopreventive and chemotherapeutic actions of mTOR inhibitor in genetically
      defined head and neck squamous cell carcinoma mouse model.
AB  - PURPOSE: To assess the efficacy of rapamycin treatment in chemoprevention and
      chemotherapy of tumorigenesis in a genetically defined mouse model of head and
      neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: Knockdown of Tgfbr1
      and/or Pten using siRNA-mediated RNA interference was carried out in human HNSCC
      cell lines to analyze molecular changes in the mTOR pathway. Tgfbr1(flox/flox);
      Pten(flox/flox); K14-CreER(tam) mice were treated with oral gavage of tamoxifen
      for the conditional deletion of Tgfbr1 and Pten in oral mucosa, resulting in
      HNSCC. Tgfbr1 and Pten conditonal deletion (2cKO) mice were treated with
      rapamycin before or after the onset of HNSCC, and the efficacy of this treatment
      was assessed by determining tumor burden, longevity, and molecular analysis of
      the mTOR pathway. Molecular changes observed in human HNSCC cell lines and 2cKO
      mice were compared to identify key alterations in the mTOR pathway. RESULTS:
      Knockdown of Tgfbr1 and/or Pten in human HNSCC cell lines resulted in activation
      of mTOR activity complex 1 and increased levels of survivin. Furthermore, we
      observed similar changes in HNSCC of the 2cKO mouse. In the human HNSCC tissue
      array, a loss of Tgfbr1 expression correlated with increased survivin levels.
      Chemopreventive rapamycin treatment significantly delayed the onset of the HNSCC
      tumors and prolonged survival in 2cKO mice. In addition, we also found that
      rapamycin had a therapeutic effect on squamous cell carcinomas in these mice. In
      2cKO HNSCC tongue tumors, rapamycin treatment induced apoptosis, inhibited cell
      proliferation and phosphorylation of Akt and S6, and decreased survivin
      expression. CONCLUSIONS: These findings indicate that tumorigenesis in 2cKO HNSCC
      is associated with activation of the Akt/mTOR/survivin pathway, and inhibition of
      this pathway by rapamycin treatment successfully ameliorates the onset and
      progression of tumorigenesis.

PMID- 22859720
TI  - Identification of galanin and its receptor GalR1 as novel determinants of
      resistance to chemotherapy and potential biomarkers in colorectal cancer.
AB  - PURPOSE: A major factor limiting the effective clinical management of colorectal
      cancer (CRC) is resistance to chemotherapy. Therefore, the identification of
      novel, therapeutically targetable mediators of resistance is vital. EXPERIMENTAL
      DESIGN: We used a CRC disease-focused microarray platform to transcriptionally
      profile chemotherapy-responsive and nonresponsive pretreatment metastatic CRC
      liver biopsies and in vitro samples, both sensitive and resistant to clinically
      relevant chemotherapeutic drugs (5-FU and oxaliplatin). Pathway and gene set
      enrichment analyses identified candidate genes within key pathways mediating drug
      resistance. Functional RNAi screening identified regulators of drug resistance.
      RESULTS: Mitogen-activated protein kinase signaling, focal adhesion, cell cycle,
      insulin signaling, and apoptosis were identified as key pathways involved in
      mediating drug resistance. The G-protein-coupled receptor galanin receptor 1
      (GalR1) was identified as a novel regulator of drug resistance. Notably,
      silencing either GalR1 or its ligand galanin induced apoptosis in drug-sensitive
      and resistant cell lines and synergistically enhanced the effects of
      chemotherapy. Mechanistically, GalR1/galanin silencing resulted in downregulation
      of the endogenous caspase-8 inhibitor FLIP(L), resulting in induction of caspase
      8-dependent apoptosis. Galanin mRNA was found to be overexpressed in colorectal
      tumors, and importantly, high galanin expression correlated with poor disease
      free survival of patients with early-stage CRC. CONCLUSION: This study shows the
      power of systems biology approaches to identify key pathways and genes that are
      functionally involved in mediating chemotherapy resistance. Moreover, we have
      identified a novel role for the GalR1/galanin receptor-ligand axis in
      chemoresistance, providing evidence to support its further evaluation as a
      potential therapeutic target and biomarker in CRC.

PMID- 22859722
TI  - Cytochrome p450 architecture and cysteine nucleophile placement impact raloxifene
      mediated mechanism-based inactivation.
AB  - The propensity for cytochrome P450 (P450) enzymes to bioactivate xenobiotics is
      governed by the inherent chemistry of the xenobiotic itself and the active site
      architecture of the P450 enzyme(s). Accessible nucleophiles in the active site or
      egress channels of the P450 enzyme have the potential of sequestering reactive
      metabolites through covalent modification, thereby limiting their exposure to
      other proteins. Raloxifene, a drug known to undergo CYP3A-mediated reactive
      metabolite formation and time-dependent inhibition in vitro, was used to explore
      the potential for bioactivation and enzyme inactivation of additional P450
      enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5). Every P450
      tested except CYP2E1 was capable of raloxifene bioactivation, based on
      glutathione adduct formation. However, raloxifene-mediated time-dependent
      inhibition only occurred in CYP2C8 and CYP3A4. Comparable inactivation kinetics
      were achieved with K(I) and k(inact) values of 0.26 MUM and 0.10 min(-1) and 0.81
      MUM and 0.20 min(-1) for CYP2C8 and CYP3A4, respectively. Proteolytic digests of
      CYP2C8 and CYP3A4 Supersomes revealed adducts to Cys225 and Cys239 for CYP2C8 and
      CYP3A4, respectively. For each P450 enzyme, proposed substrate/metabolite access
      channels were mapped and active site cysteines were identified, which revealed
      that only CYP2C8 and CYP3A4 possess accessible cysteine residues near the active
      site cavities, a result consistent with the observed kinetics. The combined data
      suggest that the extent of bioactivation across P450 enzymes does not correlate
      with P450 inactivation. In addition, multiple factors contribute to the ability
      of reactive metabolites to form apo-adducts with P450 enzymes.

PMID- 22859721
TI  - In silico and intuitive predictions of CYP46A1 inhibition by marketed drugs with
      subsequent enzyme crystallization in complex with fluvoxamine.
AB  - Cytochrome P450 46A1 (cholesterol 24-hydroxylase) is an important brain enzyme
      that may be inhibited by structurally distinct pharmaceutical agents both in
      vitro and in vivo. To identify additional inhibitors of CYP46A1 among U.S. Food
      and Drug Administration-approved therapeutic agents, we used in silico and
      intuitive predictions and evaluated some of the predicted binders in the enzyme
      and spectral binding assays. We tested a total of 298 marketed drugs for the
      inhibition of CYP46A1-mediated cholesterol hydroxylation in vitro and found that
      13 of them reduce CYP46A1 activity by >50%. Of these 13 inhibitors, 7 elicited a
      spectral response in CYP46A1 with apparent spectral K(d) values in a low
      micromolar range. One of the identified tight binders, the widely used
      antidepressant fluvoxamine, was cocrystallized with CYP46A1. The structure of
      this complex was determined at a 2.5 A resolution and revealed the details of
      drug binding to the CYP46A1 active site. The NH(2)-containing arm of the Y-shaped
      fluvoxamine coordinates the CYP46A1 heme iron, whereas the methoxy-containing arm
      points away from the heme group and has multiple hydrophobic interactions with
      aliphatic amino acid residues. The CF(3)-phenyl ring faces the entrance to the
      substrate access channel and has contacts with the aromatic side chains. The
      crystal structure suggests that only certain drug conformers can enter the P450
      substrate access channel and reach the active site. Once inside the active site,
      the conformer probably further adjusts its configuration and elicits the movement
      of the protein side chains.

PMID- 22859724
TI  - 'Clinically definite benign multiple sclerosis', an unwarranted conceptual
      hodgepodge: evidence from a 30-year observational study.
AB  - BACKGROUND: Benign multiple sclerosis (BMS) is a controversial concept which is
      still debated. However identification of this kind of patients is crucial to
      prevent them from unnecessary exposure to aggressive and/or long term medical
      treatments. OBJECTIVES: To assess two definitions of 'clinically definite benign
      multiple sclerosis' (CDBMS) using long-term follow-up data, and to look for
      prognostic factors of CDBMS. METHODS: In 874 patients with definite relapsing
      remitting MS, followed up for at least 10 years, disability was assessed using
      the Disability Status Scale (DSS). CDBMS was defined by either DSS score<=2
      (CDBMS1 group) or DSS score<= 3 (CDBMS2 group) at 10 years. We estimated the
      proportion of patients who were still benign at 20 and 30 years after clinical
      onset. RESULTS: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1
      and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252)
      of cases were still benign 10 years later, and 41.1% (23/56) after an additional
      decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the
      CDBMS2 group. CONCLUSIONS: This 30-year observational study, which is one of the
      largest published series, indicates that favourable 10-year disability scores of
      DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After
      every decade almost half of the CDBMS were no longer benign. CDBMS, as currently
      defined, is an unwarranted conceptual hodgepodge. Other criteria using new
      biomarkers (genetic, biologic or MRI) should be found to detect benign cases of
      MS.

PMID- 22859723
TI  - Identification and pharmacological characterization of multiple allosteric
      binding sites on the free fatty acid 1 receptor.
AB  - Activation of FFA1 (GPR40), a member of G protein-coupling receptor family A, is
      mediated by medium- and long-chain fatty acids and leads to amplification of
      glucose-stimulated insulin secretion, suggesting a potential role for free fatty
      acid 1 (FFA1) as a target for type 2 diabetes. It was assumed previously that
      there is a single binding site for fatty acids and synthetic FFA1 agonists.
      However, using members of two chemical series of partial and full agonists that
      have been identified, radioligand binding interaction studies revealed that the
      full agonists do not bind to the same site as the partial agonists but exhibit
      positive heterotropic cooperativity. Analysis of functional data reveals positive
      functional cooperativity between the full agonists and partial agonists in
      various functional assays (in vitro and ex vivo) and also in vivo. Furthermore,
      the endogenous fatty acid docosahexaenoic acid (DHA) shows negative or neutral
      cooperativity with members of both series of agonists in binding assays but
      displays positive cooperativity in functional assays. Another synthetic agonist
      is allosteric with members of both agonist series, but apparently competitive
      with DHA. Therefore, there appear to be three allosterically linked binding sites
      on FFA1 with agonists specific for each of these sites. Activation of free fatty
      acid 1 receptor (FFAR1) by each of these agonists is differentially affected by
      mutations of two arginine residues, previously found to be important for FFAR1
      binding and activation. These ligands with their high potencies and strong
      positive functional cooperativity with endogenous fatty acids, demonstrated in
      vitro and in vivo, have the potential to deliver therapeutic benefits.

PMID- 22859725
TI  - Immunoglobulin A deficiency on serological coeliac screening: an opportunity for
      early diagnosis of hypogammaglobulinaemia.
AB  - We present a serendipitous case of clinically significant pan
      hypogammaglobulinaemia, diagnosed after routine serological testing for possible
      coeliac disease led first to identification of IgA deficiency (discovered as a
      low background in IgA-based routine serological screening), and subsequently to
      confirmed pan-hypogammaglobulinaemia (antibody immunodeficiency).
      Hypogammaglobulinaemia is a relatively rare diagnosis (estimated at 1 in 36,000),
      in which delayed diagnosis and treatment are associated with chronic organ damage
      including bronchiectasis. Routine serological testing for coeliac disease using
      the IgA anti-tissue transglutaminase (IgA TTG) test is in widespread use and
      provides an opportunity for early diagnosis of hypogammaglobulinaemia. Routine
      serological screening for coeliac disease may uncover IgA deficiency, and we
      suggest that all IgA-deficient cases identified should also be checked for
      antibody deficiency by quantifying the other immunoglobulins (IgG, IgM).

PMID- 22859726
TI  - The analytic impact of a reduced centrifugation step on chemistry and
      immunochemistry assays: an evaluation of the Modular Pre-Analytics.
AB  - BACKGROUND: The COBAS 6000 system can be completed by a Modular Pre-Analytics
      (MPA), an integrated laboratory automation system that streamlines preanalysis.
      For an optimal throughput, the MPA centrifuges blood collection tubes for 5 min
      at 1885 * g - a centrifugation time that is not in concordance with the World
      Health Organization guidelines which suggest centrifugation for 10/15 min at 2000
      3000 * g. METHODS: In this study, the analytical outcome of 50 serum and 50
      plasma samples centrifuged for 5 or 10 min at 1885 * g was investigated. The
      study included routine chemistry and immunochemistry assays on the COBAS 6000 and
      the Minicap capillary electrophoresis. RESULTS: Deming-fit and Bland-Altman plots
      of the 5-min and 10-min centrifugation steps indicated a significant correlation
      in serum samples. The lipaemia index in plasma samples centrifuged for 5 min
      displayed a statistically significant variation when compared with the 10-min
      centrifugation. CONCLUSIONS: Preanalytical centrifugation can be successfully
      down-scaled to a duration of 5 min for most routine chemistry and immunochemistry
      assays in serum and plasma samples. To prevent inaccurate results in plasma
      samples with an increased lipaemia index from being reported, the laboratory
      information system was programmed to withhold results above certain lipaemia
      indices. The presented data support the use of a 5-min centrifugation step to
      improve turnaround times, thereby meeting one of the desires of the requesting
      clinicians.

PMID- 22859727
TI  - Estimating resting energy expenditure with a portable armband device in an
      ambulatory setting.
AB  - BACKGROUND: The measurement of resting energy expenditure (REE) in an ambulatory
      setting raises methodological problems. Therefore, the use of predictive
      equations for the estimation of REE is common. Alternatively, the measurement of
      sleeping energy expenditure (SEE) has been proposed. The authors retrospectively
      analyzed data on SEE assessed with a portable armband (PA) device in an
      ambulatory setting and evaluated this approach against predictive equations and
      REE measured by indirect calorimetry (IC). METHODS: REE was measured with IC, and
      SEE was assessed with the PA using standardized conditions in 81 participants
      (aged 46 +/- 13 years) over a wide range of body weight (mean body mass index
      [BMI] 36.4 +/- 9.3 kg/m(2); range, 21.6-55.7). RESULTS: SEE (1756 +/- 393 kcal/d)
      was 7.6% higher than REE (1632 +/- 346 kcal/d) (P < .001). This difference (123
      +/- 214 kcal/d) was smaller than that using the predictive equation for REE by
      Harris and Benedict (207 +/- 217 kcal/d) and the BMI group-specific equations
      according to Muller et al (209 +/- 190 kcal/d). Linear regression analysis was
      significant (r (2) = 0.705; P < .001). SEE showed similar 95% confidence
      intervals compared with both of the predictive equations. CONCLUSIONS: The
      described standardized assessment of SEE by a PA device appears to be a promising
      approach to estimate REE in an ambulatory setting. SEE reflects REE at least as
      precisely as the predictive equations.

PMID- 22859728
TI  - Clinical utility of lipoprotein-associated phospholipase A2 for cardiovascular
      disease prediction in a multiethnic cohort of women.
AB  - BACKGROUND: Findings regarding the association of lipoprotein-associated
      phospholipase A2 (Lp-PLA2) activity and mass with incident cardiovascular disease
      (CVD) have been inconsistent, and their role in risk prediction is uncertain.
      METHODS: A case-cohort sample from the Women's Health Initiative Observational
      Study (WHI-OS) comprised 1821 CVD cases and a reference subcohort of 1992 women.
      We used Cox regression models with inverse sampling weights to assess the
      association of Lp-PLA2 mass and activity with CVD (myocardial infarction, stroke,
      and CVD mortality). RESULTS: Subcohort means were 184.3 mmol/min/mL for Lp-PLA2
      activity and 499.2 MUg/L for Lp-PLA2 mass, with 99% having mass above 200 MUg/L,
      the clinically recommended cut point. Both activity and mass were positively
      associated with incident CVD in age- and race/ethnicity-adjusted analyses.
      Following adjustment according to CVD risk factors, the association with activity
      became null (hazard ratio = 1.02 for top vs bottom quartile, 95% CI = 0.79-1.33,
      P for trend = 0.65), but the association with mass remained (hazard ratio = 1.84,
      95% CI = 1.45-2.34, P for trend < 0.0001). In contrast to blood pressure, HDL,
      and hsCRP, reclassification statistics for Lp-PLA2 mass did not suggest
      improvement for overall CVD after full adjustment. CONCLUSIONS: In the WHI-OS Lp
      PLA2 mass, but not activity, was independently associated with CVD. However,
      model fit did not significantly improve with Lp-PLA2 mass, and assay calibration
      remains a clinical concern.

PMID- 22859731
TI  - Methanomassiliicoccus luminyensis gen. nov., sp. nov., a methanogenic archaeon
      isolated from human faeces.
AB  - During attempts to obtain novel, human-associated species of the domain Archaea,
      a coccoid micro-organism, designated strain B10(T), was isolated in pure culture
      from a sample of human faeces collected in Marseille, France. On the basis of its
      phenotypic characteristics and 16S rRNA and mcrA gene sequences, the novel strain
      was classified as a methanogenic archaeon. Cells of the strain were non-motile,
      Gram-staining-positive cocci that were approximately 850 nm in diameter and
      showed autofluorescence at 420 nm. Cells were lysed by 0.1% (w/v) SDS. With
      hydrogen as the electron donor, strain B10(T) produced methane by reducing
      methanol. The novel strain was unable to produce methane when hydrogen or
      methanol was the sole energy source. In an atmosphere containing CO(2), strain
      B10(T) could not produce methane from formate, acetate, trimethylamine, 2
      butanol, 2-propanol, cyclopentanol, 2-pentanol, ethanol, 1-propanol or 2,3
      butanediol. Strain B10(T) grew optimally with 0.5-1.0% (w/v) NaCl, at pH 7.6 and
      at 37  degrees C. It required tungstate-selenite for growth. The complete genome
      of the novel strain was sequenced; the size of the genome was estimated to be
      2.05 Mb and the genomic DNA G+C content was 59.93 mol%. In phylogenetic analyses
      based on 16S rRNA gene sequences, the highest sequence similarities (98.0-98.7%)
      were seen between strain B10(T) and several uncultured, methanogenic Archaea that
      had been collected from the digestive tracts of a cockroach, a chicken and
      mammals. In the same analysis, the non-methanogenic 'Candidatus Aciduliprofundum
      boonei' DSM 19572 was identified as the cultured micro-organism that was most
      closely related to strain B10(T) (83.0% 16S rRNA gene sequence similarity). Each
      of the three treeing algorithms used in the analysis of 16S rRNA gene sequences
      indicated that strain B10(T) belongs to a novel order that is distinct from the
      Thermoplasmatales. The novel strain also appeared to be distinct from
      Methanosphaera stadtmanae DSM 3091(T) (72.9% 16S rRNA gene sequence similarity),
      another methanogenic archaeon that was isolated from human faeces and can use
      methanol in the presence of hydrogen. Based on the genetic and phenotypic
      evidence, strain B10(T) represents a novel species of a new genus for which the
      name Methanomassiliicoccus luminyensis gen. nov., sp. nov. is proposed. The type
      strain of the type species is B10(T) ( = DSM 24529(T) = CSUR P135(T)).

PMID- 22859729
TI  - Plasma adiponectin and the risk of hypertension in white and black postmenopausal
      women.
AB  - BACKGROUND: Adiponectin may have a protective role in the development of obesity
      related metabolic and vascular disorders, including hypertension. We conducted a
      prospective, nested case control study to investigate the relation between
      baseline plasma adiponectin, measures of adiposity, and subsequent risk of
      hypertension. METHODS: We selected 400 white and 400 black postmenopausal women,
      age <70 years, who developed incident hypertension during 5.9-year follow-up and
      an equal number of age- and race-matched controls in the Women's Health
      Initiative Observational Study. We measured plasma concentrations of total
      adiponectin in their baseline blood samples. RESULTS: In crude matched models,
      plasma adiponectin was inversely associated with risk of hypertension among both
      white and black women. The association appeared to be nonlinear in white women
      but dose related in black women. Adjustment for lifestyle factors, measures of
      obesity, and obesity-related clinical factors attenuated these associations. The
      multivariable relative risk (95% CI) of hypertension across increasing quartiles
      of plasma adiponectin were 1.00, 0.98 (0.66-1.46), 0.63 (0.41-0.97), and 0.92
      (0.60-1.42) in white women (P(trend): 0.38) and 1.00, 0.96 (0.64-1.46), 0.83
      (0.53-1.29), and 0.58 (0.36-0.94) in black women (P(trend): 0.02). Further
      adjustment for inflammatory markers and endothelial markers eliminated the
      association in white, but not black, women. CONCLUSIONS: In this prospective,
      nested case control study, we found an inverse association between plasma
      adiponectin and risk of hypertension in white and black postmenopausal women. The
      reduced risk of hypertension was limited to only intermediate concentrations of
      adiponectin in white women whereas it was graded across quartiles of adiponectin
      in black women.

PMID- 22859732
TI  - Improved growth and stress tolerance in the Arabidopsis oxt1 mutant triggered by
      altered adenine metabolism.
AB  - Plants perceive and respond to environmental stresses with complex mechanisms
      that are often associated with the activation of antioxidant defenses. A genetic
      screen aimed at isolating oxidative stress-tolerant lines of Arabidopsis thaliana
      has identified oxt1, a line that exhibits improved tolerance to oxidative stress
      and elevated temperature but displays no apparent deleterious growth effects
      under non-stress conditions. Oxt1 harbors a mutation that arises from the altered
      expression of a gene encoding adenine phosphoribosyltransferase (APT1), an enzyme
      that converts adenine to adenosine monophosphate (AMP), indicating a link between
      purine metabolism, whole-plant growth responses, and stress acclimation. The oxt1
      mutation results in decreased APT1 expression that leads to reduced enzymatic
      activity. Correspondingly, oxt1 plants possess elevated levels of adenine.
      Decreased APT enzyme activity directly correlates with stress resistance in
      transgenic lines that ectopically express APT1. The metabolic alteration in oxt1
      plants also alters the expression of several antioxidant defense genes and the
      response of these genes to oxidative challenge. Finally, it is shown that
      manipulation of adenine levels can induce stress tolerance to wild-type plants.
      Collectively, these results show that alterations in cellular adenine levels can
      trigger stress tolerance and improve growth, leading to increases in plant
      biomass. The results also suggest that adenine might play a part in the signals
      that modulate responses to abiotic stress and plant growth.

PMID- 22859733
TI  - Poplar extrafloral nectar is protected against plant and human pathogenic fungus.

PMID- 22859734
TI  - DNA-binding domain of AtTRB2 reveals unique features of a single Myb histone
      protein family that binds to both Arabidopsis- and human-type telomeric DNA
      sequences.

PMID- 22859735
TI  - Intrinsic properties of Tcf1 and Tcf4 splice variants determine cell-type
      specific Wnt/beta-catenin target gene expression.
AB  - T-cell factor (Tcf)/lymphoid-enhancer factor (Lef) proteins are a structurally
      diverse family of deoxyribonucleic acid-binding proteins that have essential
      nuclear functions in Wnt/beta-catenin signalling. Expression of Wnt/beta-catenin
      target genes is highly dependent on context, but the precise role of Tcf/Lef
      family members in the generation and maintenance of cell-type-specific Wnt/beta
      catenin responses is unknown. Herein, we show that induction of a subset of
      Wnt/beta-catenin targets in embryonic stem cells depends on Tcf1 and Tcf4,
      whereas other co-expressed Tcf/Lef family members cannot induce these targets.
      The Tcf1/Tcf4-dependent gene responses to Wnt are primarily if not exclusively
      mediated by C-clamp-containing Tcf1E and Tcf4E splice variants. A combined
      knockdown of Tcf1/Tcf4 abrogates Wnt-inducible transcription but does not affect
      the active chromatin conformation of their targets. Thus, the transcriptionally
      poised state of Wnt/beta-catenin targets is maintained independent of Tcf/Lef
      proteins. Conversely, ectopically overexpressed Tcf1E cannot invade silent
      chromatin and fails to initiate expression of inactive Wnt/beta-catenin targets
      even if repressive chromatin modifications are abolished. The observed non
      redundant functions of Tcf1/Tcf4 isoforms in acute transcriptional activation
      demonstrated that the cell-type-specific complement of Tcf/Lef proteins is a
      critical determinant of context-dependent Wnt/beta-catenin responses. Moreover,
      the apparent inability to cope with chromatin uncovers an intrinsic property of
      Tcf/Lef proteins that prevents false ectopic induction and ensures spatiotemporal
      stability of Wnt/beta-catenin target gene expression.

PMID- 22859736
TI  - Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase
      I transcription.
AB  - Nucleolin is a multi-functional nucleolar protein that is required for ribosomal
      RNA gene (rRNA) transcription in vivo, but the mechanism by which nucleolin
      modulates RNA polymerase I (RNAPI) transcription is not well understood.
      Nucleolin depletion results in an increase in the heterochromatin mark H3K9me2
      and a decrease in H4K12Ac and H3K4me3 euchromatin histone marks in rRNA genes.
      ChIP-seq experiments identified an enrichment of nucleolin in the ribosomal DNA
      (rDNA) coding and promoter region. Nucleolin is preferentially associated with
      unmethylated rRNA genes and its depletion leads to the accumulation of RNAPI at
      the beginning of the transcription unit and a decrease in UBF along the coding
      and promoter regions. Nucleolin is able to affect the binding of transcription
      termination factor-1 on the promoter-proximal terminator T0, thus inhibiting the
      recruitment of TIP5 and HDAC1 and the establishment of a repressive
      heterochromatin state. These results reveal the importance of nucleolin for the
      maintenance of the euchromatin state and transcription elongation of rDNA.

PMID- 22859738
TI  - Dose-dependent response of dendritic cells to 7-thia-8-oxo-guanosine and its
      modulation by polyinosinic:polycytidylic acid.
AB  - Targeting the endosomal Toll-like receptors (TLRs) by specific agonists seems to
      be a promising tool for stimulation of the immunogenicity of dendritic cells
      (DCs). Since the functional outcome upon the engagement of TLRs may be different,
      the aim of our study was to examine if and how different concentrations of 7-thia
      8-oxo-guanosine (7-TOG), a selective TLR7 agonist, influence differentiation,
      maturation and functions of human monocyte-derived DCs (MoDCs) and if its effects
      on MoDCs could be modulated by co-ligation of TLR3. Immature MoDCs were treated
      with different concentrations of 7-TOG (25, 100 and 250 MUmol/L) alone, or
      together with polyinosinic:polycytidylic acid, Poly (I:C) (10 ng/mL), a selective
      TLR3 agonist, for an additional 48 h. We showed that the highest concentration of
      7-TOG stimulated the differentiation, maturation and allostimulatory capability
      of MoDCs. These changes were accompanied by an increased production of
      interleukin 12 (IL-12) and induction of T helper (Th)1 and Th17 immune responses.
      Both Th responses were significantly augmented by additional stimulation of MoDCs
      with Poly (I:C). The treatment of MoDCs with the intermediate concentration of 7
      TOG resulted in the up-regulation of co-stimulatory molecule (CD86) and increased
      production of IL-1beta and IL-6 by MoDCs, followed by the stimulation of the Th17
      immune response. The lowest concentration of 7-TOG down-regulated the expression
      of CD40 on MoDCs and potentiated the Th2 immune response. The Th2 response was
      not significantly modulated by additional treatment of MoDCs with Poly (I:C), but
      this combination of TLR3/TLR7 agonists also stimulated both Th1 and Th17
      responses. In conclusion, our results show that 7-TOG influences the phenotype
      and functions of MoDCs in a dose-dependent manner and suggests that fine-tuned
      signaling through TLR7 may be modified by the engagement of TLR3, resulting in a
      different outcome of immune response.

PMID- 22859737
TI  - Sphingosine kinase isoforms as a therapeutic target in endocrine therapy
      resistant luminal and basal-A breast cancer.
AB  - Sphingosine kinase signaling has become of increasing interest as a cancer target
      in recent years. Two sphingosine kinase inhibitors, sphingosine kinase inhibitor
      (SKI)-II and ABC294640, are promising as potential breast cancer therapies.
      However, evidence for their therapeutic properties in specific breast cancer
      subtypes is currently lacking. In this study, we characterize these drugs in
      luminal, endocrine-resistant (MDA-MB-361) and basal-A, triple-negative (MDA-MB
      468) breast cancer cells and compare them with previously published data in other
      breast cancer cell models. Both SKI-II and ABC294640 demonstrated greater
      efficacy in basal-A compared with luminal breast cancer. ABC294640, in
      particular, induced apoptosis and blocked proliferation both in vitro and in vivo
      in this triple-negative breast cancer system. Furthermore, Sphk expression
      promotes survival and endocrine therapy resistance in previously sensitive breast
      cancer cells. Taken together, these results characterize sphingosine kinase
      inhibitors across breast cancer cell systems and demonstrate their therapeutic
      potential as anti-cancer agents.

PMID- 22859739
TI  - Manganese in cerebrospinal fluid and blood plasma of patients with amyotrophic
      lateral sclerosis.
AB  - Neurotoxic properties of manganese (Mn) are well documented. It is less known
      that Mn contributes to the development of neurodegenerative disorders in the
      general population. This study presents Mn data from patients with amyotrophic
      lateral sclerosis (ALS) in a well-defined cohort diagnosed by
      electrophysiological methods. Cerebrospinal fluid (CSF) and plasma were collected
      from patients and controls. Mn concentrations were analyzed by high-resolution
      inductively coupled plasma mass spectrometry. Concentrations of Mn were
      significantly higher in ALS CSF (median 5.67 MUg/L) than in CSF from controls
      (median 2.08 MUg/L). Also, ALS CSF Mn concentrations were higher than ALS plasma
      Mn concentrations (median 0.91 MUg/L), suggesting transport of Mn into the
      central nervous system. The properties of barrier systems between blood and the
      brain are discussed and the possibility of Mn accumulation contributing to the
      relentless course of ALS is introduced.

PMID- 22859740
TI  - Porosome: the secretory portal.
AB  - 'It seems terribly wasteful that, during the release of hormones and
      neurotransmitters from a cell, the membrane of a vesicle should merge with the
      plasma membrane to be retrieved for recycling only seconds or minutes later.' -
      Erwin Neher, Nature 1993;363:497-498. This insightful statement so appropriately
      put, clearly reflected on the perception that secretory vesicles completely merge
      at the cell plasma membrane, failing to justify the generation of partially empty
      secretory vesicles in cells following secretion. A rational cellular mechanism
      would employ the transient fusion of secretory vesicles at the cell plasma
      membrane without compromising vesicle integrity, combined with vesicle retrieval
      following partial discharge of contents, to generate such partially empty
      vesicles following secretion. This hypothesis was finally confirmed with the
      serendipitous discovery of the porosome almost 16 years ago. The porosome has
      been demonstrated to be the universal secretory portal in cells and is present at
      the cell plasma membrane. In the past decade, the composition of the porosome,
      its dynamics, its structure at nanometer resolution in realtime using atomic
      force and electron microscopy, and its functional reconstitution into artificial
      lipid membrane, has resulted in a paradigm shift and a molecular understanding of
      the secretory process in cells. A brief background on porosome discovery, and our
      current understanding of its structure and function is summarized in this
      Minireview.

PMID- 22859741
TI  - Effect of angle of incidence on macular thickness and volume measurements
      obtained by spectral-domain optical coherence tomography.
AB  - PURPOSE: Evaluation of the effect of angle of incidence on macular thickness and
      volume measurements obtained by spectral-domain optical coherence tomography
      (OCT). METHODS: A total of 30 eyes from 15 healthy young subjects underwent
      macular cube volume scans (512 * 128 protocol) following dilation using the
      Cirrus spectral domain OCT. For each eye, scans were obtained by positioning the
      scanning beam in the center of the dilated pupil, as well as in four eccentric
      positions (approximately 3 mm from the center), superior, inferior, nasal, and
      temporal to the pupillary center, to create oblique angles of incidence between
      the light beam and retina. In all cases, the region scanned by the volume cube
      was centered on the fovea. Macular thickness and volume measurements were
      computed for volume scan acquisitions, and differences in values between
      eccentric scans and the central scan were analyzed. RESULTS: Retinal thickness
      and volume values were observed to increase significantly in all subfields for
      all eccentrically-obtained scans compared to scans obtained through the center of
      the pupil. The mean increase in thickness for the various scan positions and
      subfields ranged from 3.76 to 11.38. Scans that were displaced temporally
      consistently showed the greatest increase in thickness and volume, whereas
      nasally positioned scans showed the least increase. The increase in retinal
      thickness for all subfields correlated significantly with angle of inclination or
      tilting of the retina. CONCLUSIONS: Macular thickness and volume measurement
      results may be affected significantly by positioning of the scanning beam in the
      pupil and resultant angle of incidence on the retina. These findings suggest that
      care should be taken to position the scanning beam consistently in the center of
      the pupil to achieve reliable measurements.

PMID- 22859742
TI  - A neurobehavioral analysis of the prevention of visual impairment in the DBA/2J
      mouse model of glaucoma.
AB  - PURPOSE: Timoptic-XE treatment was used to examine the relationship between age
      related changes in intraocular pressure (IOP), retinal cell loss, visual ability,
      and neuronal labeling in the superior colliculus in the DBA/2J mouse model of
      pigmentary glaucoma. METHODS: Mice were administered Timoptic-XE (0.0%, 0.25%, or
      0.50%) daily from 9 weeks to 12 months of age. Visual ability and IOP were
      evaluated at 3, 6, 9, and 12 months of age. Mice from each group were then given
      intraocular injections of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP), and estimates of the number of cells in the ganglion cell
      layer of the retina, WGA-HRP transneural labeling of cells, cell count, and cross
      sectional area of Nissl-stained cells in the superior colliculus were obtained.
      RESULTS: Mice treated with 0.50% and 0.25% Timoptic-XE maintained a high level of
      performance in behavioral vision tasks, while 12-month-old untreated mice (0.0%
      Timoptic-XE) exhibited impaired visual performance. Timoptic-XE therapy reduced
      IOP and cell loss in the ganglion cell layer of the retina and prevented somal
      shrinkage and the decrease in WGA-HRP transneural labeling in the superior
      colliculus that occurred in untreated mice at 12 months of age. CONCLUSIONS: This
      study provides a comprehensive assessment of the efficacy of Timoptic-XE in
      DBA/2J mice by correlating age-related visual system changes in the retina and
      brain with changes in IOP and visual ability. These results showed that reducing
      IOP not only rescued retinal ganglion cell atrophy but also restored visual
      function and altered patterns of neurodegeneration that occur with blindness.

PMID- 22859744
TI  - Urinary biomarkers in obstructive nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Obstructive nephropathy is a leading cause of CKD in
      children. The assessment of severity of renal impairment and the prediction of
      which children will progress to renal failure are, however, challenging. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This case-control study measured the
      urinary excretion of candidate biomarkers in 27 prevalent case-patients with
      posterior urethral valves (PUVs) and 20 age-matched controls, correlated their
      urinary concentration with GFR, and analyzed receiver-operating characteristic
      (ROC) curve and regression analyses to assess their performance as tests for low
      GFR. RESULTS: The median urinary protein-to-creatinine ratio was higher in
      children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol;
      range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = 
      0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly
      decreased, whereas that of TGFbeta and L1 cell adhesion molecule (L1CAM) was
      significantly increased. Whole-urine TGFbeta excretion correlated inversely with
      GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFbeta, L1CAM, and
      urinary protein-to-creatinine ratio performed best, with areas under the ROC
      curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis,
      whole-urine TGFbeta, L1CAM, and urinary protein-to-creatinine ratio were
      associated with low GFR in the case-patients. CONCLUSIONS: Candidate biomarkers
      of obstructive nephropathy can be readily measured in whole urine and in urine
      exosomes. In boys with PUV, these biomarkers correlate with GFR.

PMID- 22859745
TI  - A case of late kidney allograft failure: a clinical pathological conference from
      American Society of Nephrology Kidney Week 2011.

PMID- 22859746
TI  - Association of reduced renal function with hepatitis B virus infection and
      elevated alanine aminotransferase.
AB  - BACKGROUND AND OBJECTIVES: Clinically, hepatitis B virus (HBV) infection is
      observed to be associated with nephropathy. However, previous population-based
      studies failed to show an association between HBV infection and CKD. Therefore,
      this cross-sectional study was designed to further explore this association.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A representative sample of 6854
      Chinese adults aged 30-75 years was tested for levels of serum hepatitis B
      surface antigen, alanine aminotransferase (ALT), creatinine, urinary
      albumin/creatinine ratio, and potential CKD risk factors. RESULTS: Neither HBV
      infection nor elevated ALT (ALT+; >= sex-specific 90th percentile of ALT levels
      of noninfected persons) was significantly associated with reduced estimated GFR
      (eGFR < 60 ml/min per 1.73 m(2)). Compared with noninfected persons, HBV-infected
      persons with ALT+, but not those with ALT- (P=0.26), were more likely to have
      reduced eGFR (odds ratio, 4.07; 95% confidence interval, 1.18-14.0; P=0.03).
      Further analysis with a general linear model revealed a significant difference in
      eGFR (mean +/- SEM) between HBV-infected and noninfected persons (87.8+/-0.8
      versus 90.2+/-0.4 ml/min per 1.73 m(2); P=0.002). This difference was mainly
      derived from that between HBV-infected persons with ALT+ and noninfected persons,
      with an average difference in eGFR of -4.5 (95% confidence interval, -0.9 to 
      8.1; P=0.01). HBV infection and ALT+, alone or in combination, were not
      significantly associated with albuminuria or CKD. CONCLUSIONS: HBV infection with
      elevated ALT, rather than HBV infection alone, was associated with reduced renal
      function.

PMID- 22859747
TI  - Vascular disease, ESRD, and death: interpreting competing risk analyses.
AB  - BACKGROUND AND OBJECTIVES: Vascular disease, a common condition in CKD, is a risk
      factor for mortality and ESRD. Optimal patient care requires accurate estimation
      and ordering of these competing risks. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This is a prospective cohort study of screened (n=885) and
      randomized participants (n=837) in the Modification of Diet in Renal Disease
      study (original study enrollment, 1989-1992), evaluating the association of
      vascular disease with ESRD and pre-ESRD mortality using standard survival
      analysis and competing risk regression. RESULTS: The method of analysis resulted
      in markedly different estimates. Cumulative incidence by standard analysis
      (censoring at the competing event) implied that, with vascular disease, the 15
      year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more
      accurate representation of absolute risk was estimated with competing risk
      regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death,
      respectively. For the association of vascular disease with pre-ESRD death,
      estimates of relative risk by the two methods were similar (standard survival
      analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20-2.20;
      competing risk regression adjusted subhazard ratio, 1.57; 95% confidence
      interval, 1.15-2.14). In contrast, the hazard and subhazard ratios differed
      substantially for other associations, such as GFR and pre-ESRD mortality.
      CONCLUSIONS: When competing events exist, absolute risk is better estimated using
      competing risk regression, but etiologic associations by this method must be
      carefully interpreted. The presence of vascular disease in CKD decreases the
      likelihood of survival to ESRD, independent of age and other risk factors.

PMID- 22859748
TI  - Association of interleg BP difference with overall and cardiovascular mortality
      in hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: An interarm BP difference has been associated with
      atherosclerosis and adverse cardiovascular outcomes. This study investigated
      whether an interleg BP difference was associated with peripheral vascular disease
      and overall and cardiovascular mortality in hemodialysis patients. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This study enrolled 210 hemodialysis
      patients from December 2006 to January 2007. Bilateral leg BPs were measured
      simultaneously by an ankle-brachial index (ABI)-form device before hemodialysis.
      RESULTS: The mean follow-up period was 4.4+/-1.5 years. ABI <0.9 and high
      brachial-ankle pulse wave velocity were independently associated with an interleg
      difference in systolic BP of >=15 mmHg or diastolic BP of >=10 mmHg. Furthermore,
      this difference was an independent predictor for overall mortality (hazard ratio
      [HR], 3.36; 95% confidence interval [CI], 1.68-6.72; P<0.01) and cardiovascular
      mortality (HR, 4.84; 95% CI, 1.84-12.71; P<0.01) after adjustment for
      demographic, clinical, and biochemical parameters. After further adjustment for
      ABI <0.9 and brachial-ankle pulse wave velocity, the relation remained
      significant to overall mortality (HR, 2.91; 95% CI, 1.28-6.64; P=0.01) and
      cardiovascular mortality (HR, 3.15; 95% CI, 1.05-9.44; P=0.04). CONCLUSIONS: A
      difference in systolic BP of >=15 mmHg or diastolic BP of >=10 mmHg between legs
      was associated with peripheral vascular disease and increased risk for overall
      and cardiovascular mortality in hemodialysis patients. Detection of an interleg
      BP difference may identify hemodialysis patients at increased risk of peripheral
      vascular disease and overall and cardiovascular mortality.

PMID- 22859749
TI  - Assessment of community-submitted ontology annotations from a novel database
      journal partnership.
AB  - As the scientific literature grows, leading to an increasing volume of published
      experimental data, so does the need to access and analyze this data using
      computational tools. The most commonly used method to convert published
      experimental data on gene function into controlled vocabulary annotations relies
      on a professional curator, employed by a model organism database or a more
      general resource such as UniProt, to read published articles and compose
      annotation statements based on the articles' contents. A more cost-effective and
      scalable approach capable of capturing gene function data across the whole range
      of biological research organisms in computable form is urgently needed. We have
      analyzed a set of ontology annotations generated through collaborations between
      the Arabidopsis Information Resource and several plant science journals. Analysis
      of the submissions entered using the online submission tool shows that most
      community annotations were well supported and the ontology terms chosen were at
      an appropriate level of specificity. Of the 503 individual annotations that were
      submitted, 97% were approved and community submissions captured 72% of all
      possible annotations. This new method for capturing experimental results in a
      computable form provides a cost-effective way to greatly increase the available
      body of annotations without sacrificing annotation quality. Database URL:
      www.arabidopsis.org.

PMID- 22859750
TI  - Feeding performance, carcass characteristics, and tenderness attributes of steers
      sorted by the Igenity tenderness panel and fed zilpaterol hydrochloride.
AB  - Steers (n = 560; initial BW = 420 +/- 26 kg) were selected from a pool of 1,040,
      using the IGENITY Profile DNA test for tenderness, sorted into 1 of 4 tenderness
      genotype (TG) groups [140 tough (TUF), 140 intermediate (INT), 140 tender (TEND),
      or 140 mixed (MXD)], and subsequently allocated into 56 pens at random, of which
      one-half (28 pens, 7 pens from each TG) were supplemented the beta-adrenergic
      agonist zilpaterol hydrochloride (ZH) and the balance fed a control ration. No TG
      * ZH interaction (P >= 0.15) occurred for any measured trait. Cattle from INT TG
      had less (P < 0.05) DMI during pretreatment (d 0 to 118) and entire trial (d 0 to
      143) periods than other TG. Cattle fed ZH had greater (P < 0.01) ADG and G:F, and
      decreased (P < 0.01) DMI during the treatment period (d 119 to 143). Cattle from
      the TEND group had greater (P < 0.01) marbling scores, increased (P < 0.02)
      calculated USDA yield grades (YG), and more (P < 0.02) calculated empty body fat
      (EBF) than TUF cattle. Cattle receiving ZH during the treatment period had
      increased (P < 0.01) HCW, dressed yield, and LM area. Additionally, cattle fed ZH
      exhibited decreased (P < 0.01) EBF, marbling, KPH, and calculated USDA YG. No
      difference (P > 0.06) in YG distributions were detected among TG, yet TEND cattle
      were represented by a greater (P < 0.01) proportion of Prime and premium Choice
      carcasses. Cattle fed ZH exhibited increased (P < 0.01) frequencies of YG 2
      carcasses and fewer (P < 0.01) YG 3, 4, and 5 carcasses concurrent with an
      increase (P < 0.04) in the percentage of Select carcasses. Longissimus steaks
      from TUF cattle had greater (P < 0.03) Warner-Bratzler Shear Force (WBSF) values
      at 7 and 14 d postmortem than steaks from INT or TEND cattle. Furthermore, ZH-fed
      cattle had increased (P < 0.01) WBSF values for all aging periods compared with
      control cattle. Frequency of steaks with WBSF values <3.9 kg (certified tender)
      were less (P < 0.05) for the TUF group. Feeding ZH resulted in fewer longissimus
      steaks (P < 0.01) with WBSF values <3.0 kg (guaranteed tender) across all aging
      periods; however, no difference in the frequency of steaks with WBSF values <3.9
      kg was found after 21 d of aging. Igenity Profile tenderness scores were
      correlated (P < 0.05) to carcass finish attributes and WBSF values. Commercially
      available tenderness panels may have the potential to allow for antemortem
      sorting of cattle into expected tenderness groupings, which could augment feeding
      management strategies and ultimately lead to increased marketing value for the
      beef system.

PMID- 22859751
TI  - Altered gene and protein expression of glucose transporter1 underlies
      dexamethasone inhibition of insulin-stimulated glucose uptake in chicken muscles.
AB  - A study was performed to characterize the effects of dexamethasone (DEX) and
      insulin administration on gene expression of glucose transporters (GLUT) in
      chicken (Gallus gallus domesticus) skeletal muscles and in cultured embryonic
      myoblasts. Three groups of 1-wk-old male chickens were randomly subjected to one
      of the following treatments for 7 d: DEX (a subcutaneous injection of 1 mg/kg BW,
      twice daily at 0800 h and 2000 h), controls (injected with saline), and pair-fed
      controls (restricted to the same feed intake as for the DEX treatment).
      Expressions of GLUT-1, GLUT-3, GLUT-8, and 18S rRNA mRNA were determined by
      quantitative reverse transcription PCR in the pectoralis major (PM) and biceps
      femoris (BF) muscles. Using chicken embryonic myoblasts (CEM), the interaction
      between DEX (200 nM) and insulin (100 nM) administration was evaluated on GLUT
      gene and GLUT-1 protein expressions and 2-deoxy-D-[1, 2-(3)H]-glucose (2-DG)
      uptake. Myoblasts were incubated with serum-free medium for 3 h in the presence
      or absence of insulin (0, 0.02, 0.1, 0.5, and 2.5 MUM). Although GLUT-1 is not
      considered an insulin-responsive GLUT in mammals, this study shows that insulin
      stimulated 2-DG uptake and GLUT-1 mRNA and protein expression in CEM (P <
      0.0001), suggesting that both are regulated in chicken skeletal muscle.
      Dexamethasone inhibited insulin-stimulated glucose uptake in CEM (P < 0.0001),
      likely accounting for insulin resistance in skeletal muscles. The results of the
      present study indicate that the altered GLUT-1 gene and protein expression may
      contribute to the insulin resistance induced by DEX treatment in chicken muscles.

PMID- 22859752
TI  - Effects of feeding modified distillers grains plus solubles on marbling
      attributes, proximate composition, and fatty acid profile of beef.
AB  - Wet distillers grains contain approximately 65% moisture. A partially dried
      product [modified distillers grains plus solubles (MDGS)] contains about 50%
      moisture. However, both have similar nutrient composition on a dry matter basis.
      The objective of this study was to investigate the effects of finishing diets
      varying in concentration of MDGS on marbling attributes, proximate composition,
      and fatty acid profile of beef. Yearling steers (n = 268) were randomly allotted
      to 36 pens, which were assigned randomly to 0, 10, 20, 30, 40 and 50% MDGS (DM
      basis) and fed for 176 d before harvest. The 48-h postmortem marbling score,
      marbling texture, and marbling distribution were assessed by a USDA grader and 1
      ribeye slice (longissimus thoracis) 7 mm thick was collected from each carcass
      for proximate and fatty acid analyses. Treatments did not significantly alter
      marbling score or marbling distribution (P >= 0.05). United States Department of
      Agriculture Choice slices had coarser marbling texture when compared with USDA
      Select. Although dietary treatment affected marbling texture, no consistent
      pattern was evident. Diets did not influence fat content, moisture, or ash of the
      ribeye (P >= 0.05). For treatments 0, 10, 30, 40 and 50%, there were positive
      linear relationships between marbling score and fat percentage in the ribeye (P
      <= 0.05), and all slopes were similar (P = 0.45). Feeding MDGS linearly increased
      stearic, linoelaidic, linoleic, linolenic, PUFA, and n-6 fatty acids. As dietary
      MDGS increased, linear decreases were observed in all n-7 fatty acids and cubic
      relationships were detected for the 18:1 trans isomers [trans-6-8-octadecenoic
      acid (6-8t), elaidic acid (9t), trans-10-octadecenoic acid (10t), and trans
      vaccenic acid (11t)]. No effects were observed for saturated fatty acids
      containing 6 to 14 carbons. Feeding MDGS resulted in increased PUFA, trans, and n
      6 fatty acids, minimal effects on marbling texture, and no effects on the
      relationship of marbling to intramuscular fat content relationship.

PMID- 22859753
TI  - Effects of reduced panel, reference origin, and genetic relationship on
      imputation of genotypes in Hereford cattle.
AB  - The objective of this study was to investigate alternative methods of designing
      and using reduced SNP panels for imputing SNP genotypes. Two purebred Hereford
      populations, an experimental population known as Line 1 Hereford (L1, n = 240)
      and registered Hereford with American Hereford Association (AHA, n = 311), were
      used. Using different reference samples of 62 to 311 animals with 39,497 SNP on
      29 autosomes and study samples of 57 or 62 animals for which genotypes were
      available for ~2,600 SNP (reduced panels), imputations were performed to predict
      the other ~36,900 loci that had been masked. An imputation package, including
      LinkPHASE and DAGPHASE, was used for imputation. Four reduced panels differing in
      minor allele frequency (MAF) and marker spacing were evaluated. Reduced panels
      included every 15th SNP across the genome (SNP_space), commercial Illumina
      Bovine3K Beadchip (SNP_3K), SNP with the highest MAF (SNP_MAF), and SNP with high
      MAF that were also evenly spaced across the genome (SNP_MS). Imputation accuracy
      was defined as the correlation of imputed genotypes and real genotypes. Reference
      samples were either from L1 or AHA. Among animals with genotypes, genetic
      relationships were estimated based on molecular marker genotypes or pedigree.
      Reduced panel design, number of animals in the reference sample, reference origin
      and genetic relationship between animals in the reference, and study samples all
      affected imputation accuracy (P < 0.001). Across genotyping schemes, imputed
      genotypes from SNP_MS had the greatest accuracy. A 0.1 increase in average
      pedigree relationship or average molecular relationship between reference and
      study samples increased imputation accuracy 10 to 20%. Using reference samples
      from the L1 population resulted in lower imputation accuracy than using reference
      samples from the admixed population AHA (P < 0.001). Increasing the number of
      animals in the reference panel by 100 individuals increased imputation accuracy
      by 8% when pedigree relationship was used as a covariate and 6% when molecular
      relationship was used as a covariate. We concluded that imputation accuracy would
      be increased through optimization of reduced panel design and genotyping
      strategy.

PMID- 22859754
TI  - Beef quality of calf-fed steers finished on varying levels of corn-based wet
      distillers grains plus solubles.
AB  - Calf-fed crossbred steers (n = 94) were randomly allocated to 3 dietary
      treatments (0%, 15%, or 30% wet distillers grains plus solubles, WDGS; DM basis)
      and fed for 167 d to determine the effects on quality attributes of beef. At 48 h
      postmortem, marbling score, marbling texture, and marbling distribution were
      assessed by a USDA grader. After grading, one rib eye slice (longissimus
      thoracis) "7 mm thick was excised from each carcass, trimmed of subcutaneous fat,
      and analyzed for fatty acid profile and lipid content. At 7 d postmortem, 48 top
      blades (infraspinatus), strip loins (longissimus lumborum), and tenderloins
      (psoas major) (16 per treatment) were removed from shoulder clods and short loins
      and 2 steaks were obtained to measure mineral content, fatty acid profile (except
      strip loins), trained sensory analysis, objective color, and lipid oxidation.
      Finishing diet did not influence the content of total lipid (P = 0.19) or
      marbling, marbling texture, or marbling distribution (P = 0.46, 0.84, 0.40,
      respectively). Feeding WDGS created a linear increase (P < 0.01) of PUFA in all
      three muscles (longissimus thoracis showed 4.90%, 5.91%, and 6.23% PUFA for 0%,
      15%, and 30% WDGS, respectively). Similar responses were observed for 18:2(n-6)
      and total n-6 fatty acids. Conversely, lower proportions of 18:1(n-7) fatty acid
      were observed in beef from animals fed 30% WDGS (P < 0.01). Total trans fatty
      acids increased linearly in strip loin and top blade steaks (P < 0.01), whereas
      proportions of 16:0 and 14:1(n-5) fatty acids decreased in all muscles (P < 0.01)
      as WDGS increased. Diet did not affect mineral content of top blades or strip
      loins. For tenderloin steaks, S concentration was lower when 30% of WDGS was fed
      (P = 0.05). No effects on sensory attributes and Warner-Bratzler shear force were
      observed (P > 0.50), except a minimal effect on strip loin juiciness (5.32, 4.86,
      and 5.52 for 0%, 15%, and 30% WDGS, respectively; P = 0.02). Top blade and
      tenderloin steaks from cattle fed 30% WDGS were significantly less red (lower a*
      values) on d 3 of simulated retail display (P < 0.04). Inclusion of 30% WDGS in
      the diet resulted in higher levels of oxidation after 7 d of retail display for
      top blade and strip loin steaks (P < 0.01). Feeding WDGS to calf-fed steers
      altered fatty acid profile, increased oxidation, and decreased color stability
      during retail display.

PMID- 22859757
TI  - Feed intake and competition in ewes on ad libitum or semi-restricted feeding of
      grass silage and hay.
AB  - The aim of the present experiment was to investigate the effect of feeding level
      and type of roughage on feed intake, feeding behavior and competition of ewes. A
      2 * 2 factorial experiment was conducted with amount of roughage available (ad
      libitum or semi restricted) and type of roughage (grass silage or hay) as main
      factors. Forty-eight ewes were randomly assigned to 8 groups of 6 ewes. All
      groups were subjected to all 4 treatments, each treatment period lasted 7 d, and
      the order of treatments was rotated systematically. The ewes were video recorded
      for the 2 last days of each treatment period and feeding and general activity
      were scored every 10 min. All aggressive interactions and displacement at the
      feed barrier were scored continuously the first 3 h after feeding. Daily feed
      intake (P < 0.0001) and DMI (P < 0.0001) were both greater in the silage than in
      the hay treatment. Ewes in the semi-restricted treatment spent less time feeding
      (P < 0.0001), had a greater individual variation in feeding time (P < 0.05) and
      spent more time queuing for feed (standing maximum 1.5 m from the feeding barrier
      with the head towards the feed; P < 0.0001). Individual data showed that 5 ewes
      fed hay and 3 ewes fed silage reduced their time spent feeding more than 50% when
      the feeding level was reduced. When fed hay, the level of feeding did not affect
      number of aggressive interactions or displacements, but when fed silage the
      number of aggressive interactions (P < 0.01) and the number of displacements (P <
      0.05) were much greater in the semi-restricted than in the ad libitum treatment.
      We conclude that even a minor restriction in the level of feeding will decrease
      time spent feeding and increase queuing and number of aggressive interactions
      when feeding space is also restricted, and that the increase in aggressive
      interactions is mainly for ewes fed grass silage.

PMID- 22859755
TI  - The effects of pure nucleotides on performance, humoral immunity, gut structure
      and numbers of intestinal bacteria of newly weaned pigs.
AB  - Weaning is often stressful for piglets and accompanied by morphological,
      histological, microbial, and immunological changes along the digestive tract.
      Dietary nucleotides are bioactive compounds which have the potential to diminish
      weaning-associated challenges. The experiment was carried out with 5 litters each
      of 7 pigs (mixed sex), weaned at 20 d of age. One baseline pig per litter was
      slaughtered at d 0. The remaining 30 pigs were housed individually and randomly
      allocated to 2 dietary treatments: the control diet or the control diet
      supplemented with a mixture of nucleotides. Measurements of growth performance
      traits included ADFI, ADG, G:F, and BW. At d 17, fresh fecal samples were taken
      to determine bacterial numbers. On d 19 and 20, pigs were slaughtered and blood
      samples were analyzed for plasma immunoglobulins and intestinal samples were
      assessed for morphological traits. Digesta from the jejunum and cecum were
      collected for analysis of the microbiome. The ADFI was greater in the nucleotide
      treatment compared with the control treatment (P < 0.05), but ADG, G:F, and BW
      did not differ between treatments. Plasma IgA concentrations increased with age
      and were greater in the nucleotide (P < 0.05) compared with the control group.
      There were no treatment differences in plasma IgG and IgM, gut morphology, or
      intestinal and fecal bacterial counts. Supplemental nucleotides may increase ADFI
      but without having any impact on growth performance of the pigs. Greater plasma
      IgA concentrations indicate that adding nucleotides in the weaning diet supported
      humoral immunity. However, there was no effect of dietary nucleotide
      supplementation on the composition of the bacterial community in parts of the
      small and large intestine. Further research is warranted before the use of
      nucleotide as a feed additive in pig diet can be recommended.

PMID- 22859758
TI  - A novel bipolar electric fence for excluding white-tailed deer from stored
      livestock feed.
AB  - Where cattle (Bos taurus) and free-ranging white-tailed deer (Odocoileus
      virginianus) coexist, they frequently share space and resources, potentially
      resulting in damage to stores of livestock feed and risk of interspecies disease
      transmission. Preventing use of stored feed by deer can be an important objective
      in farm management, depending on amount of damage experienced and perceived risk
      of disease transmission. Woven wire fences (2.4 to 3.0 m high) are generally
      considered to be the most effective means for excluding deer. However, rapidly
      deployable temporary means of excluding deer could be useful, especially during
      late winter when deer are most physiologically stressed and motivated to consume
      feed meant for cattle. Thus, the objective of this study was to evaluate a novel
      1.2-m-tall electric fence consisting of 4 strands of bipolar tape (not requiring
      separate ground wires or animal contact with ground) for excluding deer from
      artificially established feed piles during late winter 2008 in northwestern
      Minnesota. To induce deer to pause, investigate the fence, and receive negative
      stimuli before attempting to jump the fence, the bipolar tape was baited with a
      viscous fluid attractive to deer. The fence was estimated to be >80% effective at
      reducing deer presence at feed piles (10 treatment sites and 11 control sites)
      given the late winter to early spring conditions. Despite the efficacy, using the
      fence as a primary means of protecting stored feed from deer in areas with known
      disease transmission risk (e.g., presence of bovine tuberculosis) is not
      recommended because risk could remain unacceptably high if even low numbers of
      deer access stored feed. Yet, the fence could be effective as immediate
      protection of stored feed in winter before a more permanent and effective
      deterrence strategy, such as woven-wire fencing, could be installed during the
      subsequent summer. The fence would also be effective for reducing deer
      depredation of stored feed, as well as gardens, small orchards, or other
      localized or seasonal resources.

PMID- 22859759
TI  - Meta-analysis of the effects of monensin in beef cattle on feed efficiency, body
      weight gain, and dry matter intake.
AB  - A meta-analysis of the impact of monensin on growing and finishing beef cattle
      was conducted after a search of the literature. A total of 40 peer-reviewed
      articles and 24 additional trial reports with monensin feeding in beef cattle
      were selected, after meeting apriori quality criteria. Data for each trial were
      extracted and analyzed using meta-analysis software in STATA. Estimated effect
      size of monensin was calculated for feed efficiency (FE), ADG, and DMI. Monensin
      use in growing and finishing beef cattle reduced DMI (P < 0.001) and improved
      both ADG (P < 0.001) and FE (P < 0.001). The average concentration of monensin in
      feed across studies was 28.1 mg/kg feed (100% DM) and this resulted in
      approximately a 6.4% (but only 2.5 to 3.5% in the last 2 decades) increase in FE,
      3% decrease in DMI, and 2.5% increase in ADG. All 3 outcomes displayed moderate
      and significant heterogeneity of monensin response (I(2), which is a measure of
      variation beyond chance, = 29% for FE, 42% for DMI, and 23% for ADG); therefore,
      random effects models were used for those outcomes. There were no single
      influential studies that overweighted the findings for any outcome. Meta
      regression analysis of the effect sizes obtained from these data showed that
      dietary factors, dose, and study design were influential in modifying effect size
      of monensin treatment. Use of corn silage in the diet influenced the effect size
      of monensin for DMI and FE, with diets containing corn silage resulting in a
      greater improvement in FE and a larger effect on reducing DMI. Studies conducted
      to assess multiple doses of monensin showed similar effects to the use of corn
      silage in the diet. Studies conducted in the United States or with higher ADG in
      control animals (>1.17 kg/d) showed less effect of monensin on ADG. Pen-level
      studies showed a greater monensin increase on ADG than did those conducted on
      individual animals. Linear effect of monensin dose was observed for FE, DMI, and
      ADG outcomes, with greater effects on improving FE and reducing DMI with larger
      doses of monensin but lesser improvement in ADG with increasing dose. These
      findings confirm that monensin improves FE in growing and finishing beef cattle,
      and that this effect is linear with dose.

PMID- 22859760
TI  - Regulation of bovine pyruvate carboxylase mRNA and promoter expression by thermal
      stress.
AB  - Pyruvate carboxylase (PC) catalyzes the rate-limiting step in gluconeogenesis
      from lactate and is a determinant of tricarboxylic acid cycle carbon flux. Bovine
      PC 5' untranslated region (UTR) mRNA variants are the products of a single PC
      gene containing 3 promoter regions (P3, P2, and P1, 5' to 3') that are responsive
      to physiological and nutritional stressors. The objective of this study was to
      determine the direct effects of thermal stress on PC mRNA and gene expression in
      bovine hepatocyte monolayer cultures, rat hepatoma (H4IIE) cells, and Madin-Darby
      bovine kidney epithelial (MDBK) cells. Hepatocytes were isolated from 3 Holstein
      bull calves and used to prepare monolayer cultures. Rat hepatoma cells and MDBK
      cells were obtained from American Type Culture Collection, Manassas, VA.
      Beginning 24 h after initial seeding, cells were subjected to either 37 degrees C
      (control) or 42 degrees C (thermal stress) for 24 h. Treatments were applied in
      triplicate in a minimum of 3 independent cell preparations. For bovine primary
      hepatocytes, endogenous expression of bovine PC mRNA increased (P < 0.1) with 24
      h of thermal stress (1.31 vs. 2.79 +/- 0.49, arbitrary units, control vs. thermal
      stress, respectively), but there was no change (P >= 0.1) in cytosolic
      phosphoenolpyruvate carboxykinase (PEPCK-C) mRNA expression. Similarly, exposure
      of MDBK cells to thermal stress increased (P < 0.1) expression of bovine PC mRNA
      without altering (P >= 0.1) PEPCK-C mRNA expression. Conversely, there was no
      effect (P >= 0.1) of thermal stress on endogenous rat PC (0.47 vs. 0.30 +/- 0.08,
      control vs. thermal stress) or PEPCK-C (1.61 vs. 1.20 +/- 0.48, arbitrary units,
      control vs. thermal stress, respectively) mRNA expressions in H4IIE cells. To
      further investigate the regulation of PC, H4IIE cells were transiently
      transfected with bovine promoter-luciferase constructs containing either P1, P2,
      or P3, and exposed to thermal stress for 23 h. Activity of P1 was suppressed (P <
      0.1) 5-fold, activity of P2 was unchanged (P >= 0.1), and activity of P3 was
      increased (P < 0.1) by 5.4-fold. These data indicate that response of bovine PC
      gene to thermal stress is through promoter regulation and suggest that there are
      unique characteristics of bovine PC promoters that may contribute to the
      physiological response to thermal stress.

PMID- 22859761
TI  - Efficiency of genomic selection in a purebred pig male line.
AB  - Stochastic simulation was used to compare the efficiency of 3 pig breeding
      schemes based on either traditional genetic evaluation or genomic evaluation. The
      simulated population contained 1,050 female and 50 male breeding animals. It was
      selected for 10 yr for a synthetic breeding goal that included 2 traits with
      equal economic weights and heritabilities of 0.2 or 0.4. The reference breeding
      scheme, named BLUP-AM, was based on the phenotyping of all candidates (13,770
      animals/yr) for Trait 1 and of relatives from 10% of the litters (270 animals/yr)
      for Trait 2 and on BLUP-Animal Model genetic evaluations. Under the first
      alternative scenario, named GE-1TP, selection was based on genomic breeding
      values (GBV) estimated with one training population (TP) made up of candidate
      relatives phenotyped for both traits, with a size increasing from 1,000 to 3,430
      over time. Under the second alternative scenario, named GE-2TP, the GBV for Trait
      2 were estimated using a TP identical to that of GE-1TP, but the GBV for Trait 1
      were estimated using a large TP made up of candidates that increased in number
      from 13,770 to 55,080 over time. Over the simulated period, both genomic breeding
      schemes generated 39 to 58% more accurate EBV for Trait 2 than the reference
      scheme, resulting in 78 to 128% (GE-1TP) and 63 to 84% (GE-2TP) greater average
      annual genetic trends for this trait. For Trait 1, GE-1TP was 18 to 24% less
      accurate than BLUP-AM, reducing average annual genetic trends by 27 to 44%. By
      contrast, GE-2TP generated 35 to 43% more accurate EBV and 8 to 22% greater
      average annual genetic trends for Trait 1 than the reference scheme.
      Consequently, GE-2TP was 27 to 33% more efficient in improving the global
      breeding goal than BLUP-AM whereas GE-1TP was globally as efficient as the
      reference scheme. Both genomic schemes reduced the inbreeding rate, the greatest
      decrease being observed for GE-2TP (-49 to -60% compared with BLUP-AM). In
      conclusion, genomic selection could substantially and durably improve the
      efficiency of pig breeding schemes in terms of reliability, genetic trends, and
      inbreeding rate without any need to modify their current structure. Even though
      it only generates a small TP, limited annual phenotyping capacity for traits
      currently only recorded on relatives would not be prohibitive. A large TP is,
      however, required to outperform the current schemes for traits recorded on the
      candidates in the latter.

PMID- 22859762
TI  - The effects of R-salbutamol on growth, carcass measures, and health of finishing
      pigs.
AB  - A pure form of salbutamol has the potential to deliver positive production
      benefits to the swine industry. The aim of this experiment was to determine the
      effects of salbutamol on growth, carcass measures, and health of finishing pigs.
      The study used 192 pigs (89 +/- 1 kg BW) housed in groups of 6 in 32 pens and
      assigned to 1 of 4 treatments: 1) control (CTL), 0 mg/kg salbutamol; 2) 2R,
      control diet with 2 mg/kg of the pure R-enantiomer of salbutamol; 3) 4R, control
      diet with 4 mg/kg of pure R-salbutamol; or 4) 8RS, control diet with 8 mg/kg of a
      50:50 mixture of the R- and S-enantiomers. All diets were offered ad libitum for
      4 wk. All pigs were weighed and pen feed intakes were recorded weekly. At
      slaughter, individual HCW and measurements of the 10th-rib loin muscle area
      (LMA), color, marbling, firmness, and back fat, last lumbar, and midline back fat
      depths were collected. Data were analyzed using Proc GLM of SAS, with pen as the
      experimental unit. Overall, 2R and 4R pigs had greater ADG than CTL pigs (P <
      0.05) and, at slaughter, were heavier than CTL pigs (P < 0.01). Overall, 8RS pigs
      had decreased ADFI (P < 0.05), and CTL pigs had poorer G:F (P < 0.001) than the
      other 3 treatments. All salbutamol-fed pigs had 5 to 6 kg greater HCW (P <
      0.001), 2% to 3% increased carcass yield (P < 0.001), 5.6 cm(2) larger LMA (P <
      0.01), 3 to 4 mm less 10th-rib back fat (P < 0.01), and 2 mm less lumbar back fat
      (P < 0.05) than CTL pigs. However, control pigs had greater loin muscle color
      scores (P < 0.05) and marbling scores (P < 0.001) than all salbutamol-treated
      pigs. Taken together, these data indicate that as little as 2 mg/kg R-salbutamol
      has a positive effect on pig growth and carcass composition. However, the effects
      of salbutamol on meat quality require further research.

PMID- 22859763
TI  - Indices of gastrointestinal fermentation and manure emissions of growing
      finishing pigs as influenced through singular or combined consumption of
      Lactobacillus plantarum and inulin.
AB  - Conventional dietary strategies to reduce pig manure odor may either be costly,
      or impede nutrient digestibility. Additionally, the response of manure odor to
      such measures may be variable, indicating a complex relationship between
      environmental pollutant and diet. We hypothesized that dietary Lactobacillus
      plantarum (LP), with or without the inclusion of a purified oligofructose
      (inulin), may reduce odor without compromising nutrient digestibility. An
      experiment with a 2 * 2 factorial arrangement of treatments was conducted to
      investigate effects of dietary inulin (0 and 12.5 g/kg) and LP (0 and 0.5 g/kg)
      on nutrient digestibility, indicators of gastrointestinal tract fermentation,
      select fecal bacteria, manure content, and ammonia and odor emissions of 28
      growing-finishing pigs (60.3 kg; n = 7/treatment). Dietary treatments had no
      effect on nutrient digestibility. Dietary treatments containing inulin had
      decreased Enterobacteriaceae (8.60 vs. 9.67 log gene copy number/g fresh feces; P
      = 0.03) when compared with unsupplemented diets. There was an interaction between
      dietary inulin concentration and LP supplementation on estimates of fecal
      Clostridia (P = 0.01). Pigs offered diets containing both inulin and LP in
      combination had increased Clostridia when compared with those offered the control
      diet. However, there was no effect of either LP or inulin fecal Clostridia when
      offered singularly. An interaction was also noted where diets supplemented with
      LP or inulin only reduced odor (P = 0.01) compared with the control diet.
      However, there was no effect of LP on manure odor emissions when offered in
      combination with inulin. In summary, this study demonstrated that dietary
      supplementation with either exogenous LP or inulin reduces manure odor but not
      when offered in combination.

PMID- 22859764
TI  - Effects of inbreeding on fighting ability measured in Aosta Chestnut and Aosta
      Black Pied cattle.
AB  - Aosta Black Pied (ABP) and Aosta Chestnut (AC) are dual-purpose cattle indigenous
      to the western Alps and famous for their fighting ability in traditional Italian
      Batailles de Reines. The present study aimed to investigate the influence of
      inbreeding on breeding values for fighting ability achieved in participants.
      Inbreeding (F) and average relatedness (AR) were obtained from the entire
      pedigree information available (19,554 and 87,967 records for ABP and AC,
      respectively). Data (n = 23,998) relating to 8,259 cows competing in years 2001
      2009 were analyzed to obtain heritability (h(2)) estimates and breeding values
      for the trait. A placement score was chosen as a phenotype for fighting ability
      and both a classical quantitative model (NORM) and its implementation, used to
      identify its indirect genetic effects (COMP), were analyzed using the expectation
      maximization-REML (EM-REML) method. The F and AR trends in animals born between
      1990 and 2009 were generally low and were greater for ABP (+0.06%/yr) than for AC
      (+0.03%/yr) populations, which also presented a greater mean F (about 2.8% +/-
      1.7% vs. 0.8% +/- 1.5% for ABP and AC, respectively) and mean AR among
      individuals (about 1.0% +/- 0.8% vs. 0.4% +/- 0.3% for ABP and AC, respectively).
      Heritability estimates from 0.083 +/- 0.036 to 0.120 +/- 0.037 were obtained
      using the NORM model, accounting for or not accounting for F, respectively.
      Similar results were obtained also for the COMP model, with h(2) estimates of
      0.12 +/- 0.037, whether or not F was taken into consideration. Linear regression
      analyses carried out on the 33 major lineages to which most of participants
      belonged (n = 6,087) revealed an overall negative trend of EBV compared with the
      increase of either F (b = -21.3, P < 0.01) or AR (b = -50.1, P < 0.01). However,
      a great variability in the relationship between EBV and F or AR was found by
      analyzing data within lineages. Despite the variability, an unfavorable effect of
      inbreeding was detected in the fighting ability trait of both ABP and AC cattle,
      and this should be carefully considered in the breeding management of both
      breeds.

PMID- 22859765
TI  - Sorting by parity to reduce aggression toward first-parity sows in group
      gestation housing systems.
AB  - Young sows are subordinate and vulnerable in group-housing systems because they
      usually lose most fights and suffer more injuries than mature sows at mixing.
      This study was conducted to evaluate effects of sorting by parity on reducing
      aggression and associated stress with the aim to improve welfare and performance
      of first-parity sows in a group-housed system. Sows and gilts (n = 180) from 6
      breeding groups were used. Within each group, 2 groups of 15 females were mixed
      in each of 2 treatment pens after weaning and remained there throughout the
      entire gestation period. The control pen consisted of 11 multiparous and 4 first
      parity sows, and the treatment pen consisted of 11 gilts and 4 first-parity sows.
      Before mixing and at the end of the gestation period, sows and gilts were weighed
      individually, assessed for BCS, and measured for backfat thickness. Injury scores
      were assessed before and 48 h after mixing and wean-to-mating intervals,
      farrowing rate, and litter performance at the subsequent farrowing were recorded
      for all females. Aggressive interactions involving first-parity sows were video
      recorded for 72 h immediately after mixing in each pen. Data were analyzed using
      the Glimmix procedure of SAS with a Poisson regression model for count data and a
      Gaussian model for continuous data. All females in treatment pens sustained fewer
      scratches (P = 0.01) after mixing than females in control pens. First-parity sows
      in treatment pens fought more frequently (P = 0.01), tended to fight for longer
      periods (P = 0.08), and won more fights (P = 0.04) of parallel pressing but had
      fewer injures (P = 0.03) after mixing, gained more BW (P = 0.01) during
      gestation, and had greater farrowing rates (P = 0.03) compared with first-parity
      sows in control pens. The results suggest that sorting by parity shielded first
      parity sows from severe injuries caused by mixing-induced aggression so that
      their welfare and performance can be improved in group housing systems.

PMID- 22859766
TI  - Effects of feeding an herbal preparation to sows on immunological performance of
      offspring.
AB  - The objective of this study was to determine the effects of feeding Chinese
      herbal ultra-fine (CHU) powder to sows during the last week of gestation and
      during the lactation period on immunological performance of the offspring. In
      this experiment, 15 pregnant sows (mean BW = 235.6 +/- 3.7 kg) were randomly
      assigned to 1 of 3 treatments including no additive (Control), 0.75% CHU powder
      (Group A), or 1.5% CHU powder (Group B) added to a maize- and soybean meal-based
      diet. Blood from 10 piglets per group was collected at d 7, d 14, or d 21 of age
      to measure serum metabolites, lymphocyte proliferating activity, and serum
      antibody and cytokine concentrations. Dietary supplementation of sows with CHU
      powder increased (P < 0.05) serum concentrations of total protein, albumin, and
      triglycerides of offspring, whereas the concentration of glucose was reduced (P <
      0.05) compared with Controls. The CHU powder enhanced (P < 0.05) serum
      concentrations of IgG in Group B offspring on d 7 and IgM in Group A offspring on
      d 7 and d 14, increased IL-10 in Group A offspring on d 7, as well as IL-2 in
      offspring from Groups A and B on all days of determination. The CHU powder
      increased interferon gamma in Group A offspring on d 14 and in Group B offspring
      on d 14 and d 21, and increased tumor necrosis factor alpha in offspring of Group
      A on d 14 and in Group B on all days surveyed. Compared with Controls, a greater
      number (P < 0.05) of T lymphocyte subpopulations were detected in Group A and B
      offspring including CD4+ cells in Group A on d 7 and d 21, CD4+ cells in Group B
      on d 14 and d 21, and CD8+ cells in Group A on d 7 and d 14. Collectively, these
      findings indicate a beneficial effect of CHU powder treatment of sows in later
      gestation and during lactation on serum metabolism and cellular and humoral
      immune responses of their offspring.

PMID- 22859767
TI  - Genetic association between body composition measured by ultrasound and visual
      scores in Brazilian Nelore cattle.
AB  - The objective of this study was to evaluate the genetic variability of body
      composition traits measured by ultrasound, growth traits, and visual scores as
      well as their genetic associations in Nelore cattle. A total of 9,765, 13,285,
      13,061, 12,811, 3,484, 3,484, 3,483, and 3,303 records of weight at time of
      ultrasound measure (W550), 12th-13th rib LM area (LMA), backfat thickness (BF),
      rump fat thickness (RF), visual scores for body structure (BS), finishing
      precocity (FP), muscling (MS), and sheath and navel characteristics (SN),
      respectively, were used. The model included contemporary group (defined as year
      and season of birth, sex, and management group) as a fixed effect and age of dam
      at calving and age of the animal (linear and quadratic effects) as covariates.
      The direct additive genetic effect was included as a random effect. The analyses
      also included 46,157 observations of BW adjusted to 120 d. The (co)variance
      components were estimated by the restricted maximum likelihood method using a
      multitrait animal model. Heritability estimates for W550, LMA, BF, RF, BS, FP,
      MS, and SN were 0.37 +/- 0.030, 0.33 +/- 0.03, 0.24 +/- 0.02, 0.28 +/- 0.03, 0.24
      +/- 0.04, 0.38 +/- 0.05, 0.29 +/- 0.05, and 0.38 +/- 0.06, respectively. The
      estimated genetic correlations between visual scores and LMA were moderate and
      positive, ranging from 0.37 to 0.44. Similar results were obtained for the
      estimated genetic correlations between FP and MS with fat thickness measures (BF
      and RF). Low genetic correlations were estimated between SN and BS and between SN
      and the body composition traits, indicating that selection for body composition
      traits and BS will not affect sheath and navel size. The estimated genetic
      correlations between weight adjusted to 120 d of age (W120) and W550 and BS were
      high (0.87 and 0.91) and moderate with LMA (0.49 and 0.55), FP (0.37 and 0.41),
      and MS (0.47 and 0.55). The visual scores and ultrasound-measured body
      composition traits have enough genetic variation for selection purposes in Nelore
      cattle. Selection based on visual scores for body structure, finishing precocity
      and muscling should lead to desired changes in body composition albeit much more
      slowly than direct selection on those traits measured by ultrasound. Selection
      for heavier BW at early ages should lead to favorable changes in yearling LM area
      and visual scores.

PMID- 22859768
TI  - Invited review: Efficacy, metabolism, and toxic responses to chlorate salts in
      food and laboratory animals.
AB  - For over 100 yr, scientists have explored uses of sodium chlorate in agricultural
      applications. Sodium chlorate is a strong oxidizer, and thus can be very
      hazardous when not handled accordingly. Nevertheless, late 19th century
      agriculturists and scientists attempted to exploit the chemical properties of
      sodium chlorate as an herbicide and food preservative. It is the herbicidal
      utility that led to subsequent use of sodium chlorate in the agricultural
      industry since then. However, in 2000, USDA-ARS scientists proposed a new and
      targeted use of sodium chlorate against enterobacteria in food animal production.
      Specifically, when orally dosed in to cattle (Bos taurus), swine (Sus scrofa),
      broilers (Gallus gallus), turkeys (Meleagris gallopavo), and sheep (Ovis aries),
      chlorate reduced the fecal shedding of common enteropathogens of the
      Enterobacteriaceae family. Subsequent to this discovery, the efficacy of chlorate
      salts has been demonstrated in numerous production classes within species. Doses
      of sodium chlorate as low as 30 mg/kg BW, but typically 50 to 150 mg/kg BW, have
      been used to demonstrate efficacy against pathogens. Single or short-duration (<3
      d) exposures to oral chlorate at concentrations < 150 mg/kg BW have not produced
      acute toxicity or clinical signs (labored breathing, methemoglobinemia) in food
      animals. In all species studied to date, the major biotransformation product of
      chlorate is chloride ion; chlorite is not present in tissues or excreta of
      chlorate dosed animals. Chlorate is rapidly eliminated in ruminants and
      nonruminants, primarily in urine; likewise, residual chlorate in tissues depletes
      rapidly. Application of any new chemical entity to food animal production carries
      with it a responsibility to understand adverse reactions that intended and
      nonintended exposures may have in target and (or) nontarget animals and an
      understanding of the pathways of elimination that occur after exposure.
      Therefore, the purpose of this review is to summarize the published data
      regarding the efficacy, metabolism, and toxicology of chlorate salts in target
      (livestock) and nontarget species.

PMID- 22859770
TI  - Selection for placental efficiency in swine: conceptus development.
AB  - The objective of this study was to evaluate correlated responses in conceptus
      development and traits physiologically relevant for placental function in swine
      from a selection experiment that resulted in differences in placental weight (PW)
      and efficiency (PE = birthweight/placental weight). Generation 3, second parity
      females from 2 lines with a history of selection on an index predicting either
      high PE (HPE) or low PE (LPE) were mated within line to produce Generation 4
      litters for evaluation at d 30, 50, 70, 90, and 110 of gestation (n = 5/line * d
      combination). Maternal and fetal traits were analyzed by using a model including
      the fixed effects of line and gestational age, and the random effect of sire
      within line. Uterine length was not different between lines at any gestational
      age, but increased (P = 0.06) from 275.0 +/- 23.1 cm at d 30 to 338.3 +/- 23.3 cm
      at d 50, and remained relatively unchanged to d 110. Fetal weight was not
      different between lines from d 30 to 90, but was less (P = 0.02) in HPE than LPE
      at d 110 (1,280.6 +/- 77.0 vs. 1,551.1 +/- 75.3 g, respectively). Crown-rump
      length was not different between lines from d 30 to 70, but tended (P = 0.09) to
      be longer in HPE than LPE at d 90 (265.8 +/- 8.8 vs. 241.2 +/- 10.6 mm,
      respectively) and was shorter (P = 0.04) in HPE than LPE at d 110 (290.6 +/- 5.0
      vs. 304.9 +/- 4.5 mm, respectively). Placental weight increased in both lines
      from d 30 to 50, at which point it remained relatively unchanged through the rest
      of pregnancy, except in LPE that showed a second increase from d 90 to 110. As a
      result, placental weight was not different between lines from d 30 to 90, but was
      less (P < 0.01) in HPE than LPE at d 110 (244.6 +/- 32.3 vs. 379.2 +/- 24.5 g,
      respectively). Line differences in placental efficiency were not significant at
      any gestational age. Implantation site length increased slowly for both lines
      from d 30 to 90, where it remained unchanged to d 110. Implantation site area was
      greater (P < 0.05) in HPE than LPE at d 30 and 50, but was not different between
      lines for the remainder of pregnancy. These results suggest that in Western
      breeds, a reduction in placental weight through selection is not accompanied by
      compensation in placental nutrient transfer and may result in decreased prenatal
      survival.

PMID- 22859769
TI  - Sampling and aging effects on beef longissimus color stability measurements.
AB  - The present study was conducted to determine the repeatability of color stability
      measurements and to evaluate relationships among color stability data collected
      under differing sampling and aging protocols. Beef (Bos taurus) carcasses (n =
      100) were selected at grading in a commercial facility, after which a LM steak
      was removed from the 13th rib of each carcass and immediately placed in simulated
      retail display. Steaks were removed from the remainder of each loin after 14
      (duplicate) and 35 d of aging and placed in display. Color attributes [L*, a*,
      b*, hue angle, chroma, K/S(572)/K/S(525), and overall color change (DeltaE)] were
      determined on d 0, 1, 4, 7, and 11 of display. Duplicate 14-d aged steaks
      differed (P < 0.05) initially with regard to L*, b*, hue angle, chroma, K/
      S(572)/K/S(525), and DeltaE. However, changes in these attributes during display
      were equivalent in the duplicate steaks. Furthermore, repeatability estimates
      were high for all attributes, particularly when measured late in the display
      period (R = 0.55 to 0.97 on d 4, 7, and 11 of display). Differences in the trends
      associated with color change of steaks removed from the carcass after grading and
      those aged for 14 d were generally insignificant. Changes in color attributes of
      steaks aged for 35 d before simulated retail display generally were much more
      rapid than those obtained after grading or those aged for 14 d. Despite
      differences in the rate of discoloration during simulated retail display, color
      attributes were moderately to highly correlated (P < 0.05) between aging
      treatments, though the degree of correlation between attributes varied across
      days of display. In steaks collected after grading and those aged for 14 d, the
      greatest correlation was observed in the latter part of the display period with
      coefficients ranging from 0.61 to 0.94 on d 4, 7, and 11 of display. The greatest
      correlation between steaks aged for 14 d and those aged for 35 d were detected in
      the middle portion of the display period, presumably because many steaks aged for
      35 d had reached an ultimate level of discoloration by d 11 of display with
      correlation coefficients ranging from 0.51 to 0.95 on d 4 and 7 of display. Thus,
      these results indicate that color stability data is highly repeatable and that,
      although aging impacts color-life, animal variation is consistent across aging
      times. Furthermore, steaks obtained from carcasses after grading can provide
      color stability evaluations applicable to steaks from aged subprimals.

PMID- 22859771
TI  - Effect of Lactobacillus plantarum CJLP243 on the growth performance and cytokine
      response of weaning pigs challenged with enterotoxigenic Escherichia coli.
AB  - The purpose of the present study was to evaluate the effect of diets containing
      Lactobacillus plantarum CJLP243 on the growth and cytokine response of weaning
      pigs (Sus scrofa) challenged with enterotoxigenic Escherichia coli (ETEC). In a
      28-d experiment (14 d before and 14 d after challenge), a total of 108 pigs at 20
      +/- 1 d of age were allotted to 1 of 6 diets. These were a control diet without
      ETEC challenge (CON) and 5 treatment diets with ETEC challenge, including a
      control diet with ETEC challenge (negative control, NC); a positive control diet
      containing antibiotics (PC); control diet plus (10(8), 10(9), or 10(10)) cfu/kg
      L. plantarum CJLP243 (T1, T2, and T3, respectively). After challenge, NC showed
      the least ADFI, whereas PC and T3 had the greatest ADFI (P = 0.002). The ADG of
      PC, T2, and T3 were greater (P = 0.001) than that of CON, NC, and T1 during wk 1
      to wk 2. During wk 3 to wk 4, a marked decline was seen in NC (P = 0.001)
      compared with CON, whereas PC and T3 showed increased ADG (P = 0.001). The
      overall ADG of PC and T3 were greater (P < 0.001) than the remaining groups. The
      PC and T3 had the greatest G:F during the second 2 wk (P = 0.002), and the
      overall 4-wk experimental period (P = 0.003). At 3 h after challenge, all groups
      except CON had greater rectal temperatures (RT; P < 0.05). The RT decreased to
      prechallenge temperatures at 9 h (PC and T3), 24 h (T1 and T2), and remained
      increased until d 7 in NC. At 7 and 14 d postinfection, the number of animals
      detected positive for ETEC by PCR assay was the greatest in NC; however, the PC
      group had the fewest ETEC-positive animals (P < 0.05), which was similar to T3.
      All challenged pigs, except T2, had greater concentrations of serum haptoglobin
      compared with CON, with the greatest concentration observed in NC (P < 0.001).
      Challenged pigs had increased serum concentrations of tumor necrosis factor alpha
      (TNF-alpha) 3 to 48 h postinfection, with the greatest concentration of TNF-alpha
      at 48 h observed in NC (P < 0.05). Similarly, greater (P < 0.05) serum
      concentrations of interferon-gamma were observed for 9 h (T1 and T3), 24 h (T2
      and PC), and 48 h (NC) postinfection. The serum concentration of IL-6 increased
      (P < 0.05) for 3 h in T3 and 24 h in NC. In conclusion, our findings suggest that
      L. plantarum CJLP243, at a concentration of 10(10) cfu/kg, may serve as a
      potential alternative to antibiotic supplementation to improve the growth and
      health performance of weaning pigs, especially during acute inflammation of the
      gut after bacterial infections.

PMID- 22859772
TI  - "Beau de Jour"--a male doctor who bought and sold sex.

PMID- 22859773
TI  - Treating prostate cancer.

PMID- 22859774
TI  - The "self funding" NHS patient: thin end of the wedge?

PMID- 22859775
TI  - What do NHS staff think about the NHS?

PMID- 22859777
TI  - Improving comparative effectiveness research.

PMID- 22859778
TI  - Job insecurity contributes to poor health.

PMID- 22859779
TI  - US presidential candidates are asked their views on key science questions.

PMID- 22859780
TI  - Olympic drug testing centre will house new L10m research facility after games.

PMID- 22859781
TI  - Monitor tones down financial restraints on providers of NHS services.

PMID- 22859784
TI  - Uganda gears up to contain Ebola epidemic as fears of spread cause panic.

PMID- 22859782
TI  - Metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ
      free rats, and streptozotocin-induced diabetic rats.
AB  - To clarify the role of the intestinal flora in the absorption and metabolism of
      mangiferin and to elucidate its metabolic fate and pharmacokinetic profile in
      diabetic rats, a systematic and comparative investigation of the metabolism and
      pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and
      streptozotocin (STZ)-induced diabetic rats was conducted. Forty-eight metabolites
      of mangiferin were detected and identified in the urine, plasma, and feces after
      oral administration (400 mg/kg). Mangiferin underwent extensive metabolism in
      conventional rats and diabetic rats, but the diabetic rats exhibited a greater
      number of metabolites compared with that of conventional rats. When the
      intestinal flora were inhibited, deglycosylation of mangiferin and sequential
      biotransformations would not occur. Pharmacokinetic studies indicated a 2.79- and
      2.35-fold increase in the plasma maximum concentration and the area under the
      concentration-time curve from 0 to 24 h of mangiferin in diabetic rats compared
      with those for conventional rats, whereas no significant differences were
      observed between conventional rats and pseudo-germ-free rats. Further real-time
      quantitative reverse transcription-polymerase chain reaction results indicated
      that the multidrug resistance (mdr) 1a level in the ileum increased, whereas its
      level in the duodenum and the mdr1b mRNA levels in the duodenum, jejunum, and
      ileum decreased in diabetic rats compared with those in conventional rats. With
      regard to the pseudo-germ-free rats, up-regulated mdr1a mRNA levels and down
      regulated mdr1b mRNA levels in the small intestines were observed. The diabetic
      status induced increased UDP-glucuronosyltransferase (UGT) 1A3, UGT1A8, UGT2B8,
      and sulfotransferase (SULT) 1A1 mRNA levels and decreased catechol-O
      methyltransferase (COMT), UGT2B6, UGT2B12, and SULT1C1 mRNA levels. These results
      might partially explain the different pharmacokinetic and metabolic disposition
      of mangiferin among conventional and model rats.

PMID- 22859785
TI  - Court upholds strict law on abortion in Arizona.

PMID- 22859786
TI  - Psychological consequences of false-positive screening mammograms in the UK.
AB  - OBJECTIVES: To identify the psychological effects of false-positive screening
      mammograms in the UK. METHODS: Systematic review of all controlled studies and
      qualitative studies of women with a false-positive screening mammogram. The
      control group participants had normal mammograms. All psychological outcomes
      including returning for routine screening were permitted. All studies had a
      narrative synthesis. RESULTS: The searches returned seven includable studies
      (7/4423). Heterogeneity was such that meta-analysis was not possible. Studies
      using disease-specific measures found that, compared to normal results, there
      could be enduring psychological distress that lasted up to 3 years; the level of
      distress was related to the degree of invasiveness of the assessment. At 3 years
      the relative risks were, further mammography, 1.28 (95% CI 0.82 to 2.00), fine
      needle aspiration 1.80 (95% CI 1.17 to 2.77), biopsy 2.07 (95% CI 1.22 to 3.52)
      and early recall 1.82 (95% CI 1.22 to 2.72). Studies that used generic measures
      of anxiety and depression found no such impact up to 3 months after screening.
      Evidence suggests that women with false-positive mammograms have an increased
      likelihood of failing to reattend for routine screening, relative risk 0.97 (95%
      CI 0.96 to 0.98) compared with women with normal mammograms. CONCLUSIONS: Having
      a false-positive screening mammogram can cause breast cancer-specific distress
      for up to 3 years. The degree of distress is related to the invasiveness of the
      assessment. Women with false-positive mammograms are less likely to return for
      routine assessment than those with normal ones.

PMID- 22859787
TI  - How a charity oversells mammography.

PMID- 22859788
TI  - Has the proteome of formalin-fixed wax-embedded tissue been unlocked?

PMID- 22859789
TI  - Glycohemoglobin not as predictive as fasting glucose as a measure of prediabetes
      in predicting proteinuria.
AB  - BACKGROUND: There is little data on the assessment of prediabetes with
      proteinuria. METHODS: This is a cross-sectional cohort study assessing
      prediabetes with proteinuria in a large Japanese population. Using a nationwide
      health checkup database of 228 778 Japanese aged >=20 years (median 66 years;
      39.3% were men; none had pre-existing cardiovascular disease), we examined the
      association between prediabetes and proteinuria (>=1+ on dipstick) separately in
      prediabetes subjects diagnosed with the new hemoglobin A1c (HbA1c) criterion only
      (PD-A1c), the impaired fasting plasma glucose only (PD-IFG) and fulfilling both
      criteria (PD-Both). RESULTS: According to the American Diabetes Association's
      (ADA's) criterion of 5.7-6.4% HbA1c and/or 100-125 mg/dL fasting plasma glucose,
      43.8% of the subjects were judged as having prediabetes. Prediabetes subjects
      were divided into subclasses of PD-A1c (53.7%), PD-IFG (21.7%) and PD-Both
      (24.5%), respectively. Therefore, 21.7% of prediabetes subjects were missed using
      the new HbA1c criterion only. Compared with subjects with normal glucose
      tolerance (as a reference), the odds ratio (OR) [95% confidence interval (95%
      CI)] for the increased risk of proteinuria (>=1+) in diabetes itself was 2.191
      (2.081-2.307) and in whole prediabetes was 1.093 (1.046-1.142); when prediabetes
      was subdivided, the OR for proteinuria in PD-IFG was 1.217 (1.140-1.300) and that
      in PD-Both was 1.249 (1.174-1.329), but that in PD-A1c was not significant, even
      after adjustment for significant covariates, such as age, sex, body mass index,
      systolic blood pressure, antihypertensive medication, eGFR, lifestyle and lipid
      profile. CONCLUSIONS: Prediabetes is a significant risk factor for proteinuria
      compared with completely normal glucose level, and subjects with prediabetes
      defined using IFG are at significantly higher risk for proteinuria than those
      defined by HbA1c only.

PMID- 22859790
TI  - Rapid resolution of severe sustained low blood pressure in haemodialysis patients
      after successful renal transplantation.
AB  - BACKGROUND: Low blood pressure occurring in the absence of volume depletion, anti
      hypertensive medication, heart failure or cortisol deficiency occurs in ~5-10% of
      haemodialysis patients, and can result in serious complications. The
      pathophysiology of this syndrome is poorly understood. METHODS: We describe eight
      cases with dialysis-associated hypotension who underwent renal transplantation.
      Four patients were severely hypotensive with a systolic blood pressure (SBP) <100
      mmHg before and during dialysis, and four had a SBP usually <100 mmHg during
      dialysis, but usually >100 mmHg between sessions. All had donor-specific human
      leukocyte antigen antibodies. Six patients underwent pre-transplant
      plasmapheresis, which was curtailed in two because of further falls in blood
      pressure. Two patients experienced clotting of their arteriovenous fistula. In
      one patient cryofiltration was used, which was tolerated without severe falls in
      the BP. The remaining patient, who had hypotension-associated retinal vein
      thrombosis before transplant, was supported with an epinephrine infusion and did
      not receive plasmapheresis. RESULTS: Post-transplant, the first patient did not
      receive pressor therapy and died from bowel ischaemia. The other seven patients
      were supported with inotropes on critical care. The administration of steroids
      did not reverse hypotension. The mean pre-treatment SBP was 96 mmHg (range 71
      110, SEM 5.0). After inotropes were withdrawn and graft function was established,
      the mean SBP was 127 mmHg (range 113-149, SEM 4.9) (P < 0.01). CONCLUSIONS: Renal
      transplantation was performed successfully and safely in patients when pressor
      therapy was used to treat severe dialysis-associated hypotension and, moreover,
      the blood pressure normalized rapidly after graft function was established.

PMID- 22859791
TI  - Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic
      review of pharmacokinetics, efficacy and safety with recommendations by European
      Renal Best Practice (ERBP).
AB  - BACKGROUND: The prevalence of major depression in stage 5 chronic kidney disease
      (CKD) varies between 14 and 30%. Patients with CKD who are depressed have a worse
      quality of life, are hospitalized more often and die sooner than those who are
      not depressed. Antidepressant drugs are effective in the general population, but
      whether they improve outcomes in CKD is uncertain. Drug pharmacokinetics are
      altered in CKD, which may necessitate dose adjustment. We aimed to systematically
      review available evidence of the pharmacokinetics, efficacy and safety of
      antidepressant drugs when used in patients with CKD3 to CKD5 (CKD3-5). METHODS:
      This is a systematic review of randomized clinical trials and observational
      studies examining antidepressants in patients with CKD3-5, regardless of whether
      or not patients are on dialysis. Through comprehensive searches of seven
      databases, we identified all studies examining pharmacokinetic properties or
      clinical outcomes in patients with CKD3-5. One author assessed studies for
      eligibility and quality and extracted all data. Antidepressant drugs were the
      studied intervention. The main outcomes were pharmacokinetic parameters, clinical
      outcomes such as response to treatment, reduction in depression severity and
      adverse events. RESULTS: We identified 28 studies evaluating pharmacokinetic
      parameters in CKD for 24 antidepressants. Sparse and heterogeneous data precluded
      informative meta-analysis. Drug clearance in CKD3-5 was markedly reduced for
      selegiline, amitriptylinoxide, venlafaxine, desvenlafaxine, milnacipran,
      bupropion, reboxetine and tianeptine. We identified one randomized controlled
      trial (RCT) in 14 patients on haemodialysis for fluoxetine versus placebo which
      showed no difference for efficacy and safety measures. One other RCT of
      escitalopram versus placebo in 62 patients on haemodialysis provided no efficacy
      data. There were nine non-randomized trials, all suggesting benefit for the
      antidepressant under investigation. Side-effects were common, but mild in most
      patients. The limitations of this review include the scarcity of randomized trial
      data, the small size of the observational studies and possibility of publication
      bias. In addition, study selection and data extraction were done by one reviewer
      only, increasing the risk for errors made in handling of the data. CONCLUSIONS:
      Dose reduction in CKD3-5 is necessary for selegiline, amitriptylinoxide,
      venlafaxine, desvenlafaxine, milnacipran, bupropion, reboxetine and tianeptine.
      The evidence on effectiveness of antidepressants versus placebo in patients with
      CKD3-5, and with the fourth edition of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV)-defined depression is insufficient, and in view of the
      high prevalence, a well-designed RCT is greatly needed.

PMID- 22859792
TI  - Immunohistochemical expression of podocyte markers in the variants of focal
      segmental glomerulosclerosis.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the most prevalent
      primary glomerulopathy in Brazil and its incidence is increasing worldwide.
      Pathogenesis is related to podocyte injury, which may be due to several factors
      including viruses, drugs, immunology. In 2004, the Columbia classification of
      FSGS identified five histologic variants of the disease: collapsing (COL), usual
      (not otherwise specified, NOS), tip lesion (TIP), perihilar (PHI) and cellular
      variant (CEL). Several studies have demonstrated molecular changes in podocytes
      of FSGS patients. This study sought to classify a large series of FSGS biopsies
      according to the Columbia classification and analyze the occurrence of
      immunohistochemical differences among the five variants. METHODS: Approximately
      131 cases of renal biopsies with a diagnosis of primary FSGS during the period
      from 1996-2006 were classified according to the criteria of Columbia and were
      then submitted to immunohistochemical staining to the following antibodies: CD10,
      WT-1, Vimentin, Synaptopodin, alpha-actinin-4, GLEPP-1, cytokeratin (CK) 8-18,
      CK19 and Ki-67. RESULTS: The FSGS classification resulted in 38.2% of NOS
      variant, in 36.6% COL, in 14.5% TIP, in 6.9% PHI and in 3.8% CEL. COL variant
      distinguished themselves among the others for having loss of expression of CD10,
      WT1 and alpha-actinin-4 (P < 0.05). Furthermore, COL gained expression of the CK8
      18 and CK19 diverging from the other variants (P < 0.05). CONCLUSIONS: COL
      variant of FSGS presented immunohistochemical characteristics that distinguished
      it from others pointing to additional studies in this area. The distinct
      immunohistochemical properties of COL might be of help in the comprehension of
      this aggressive form of FSGS.

PMID- 22859793
TI  - Diagnosis of acute pyelonephritis with recent trends in management.

PMID- 22859794
TI  - The effect of low glucose degradation product, neutral pH versus standard
      peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial.
AB  - BACKGROUND: The balANZ trial recently reported that neutral pH, low glucose
      degradation product (biocompatible) peritoneal dialysis (PD) solutions
      significantly delayed anuria and reduced peritonitis rates compared with
      conventional solutions. This article reports a secondary outcome analysis of the
      balANZ trial with respect to peritoneal membrane function. METHODS: Adult,
      incident PD patients with residual renal function were randomized to receive
      either biocompatible or conventional (control) PD solutions for 2 years.
      Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months.
      Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3,
      6, 9, 12, 18 and 24 months. RESULTS: Of the 185 patients recruited into the
      trial, 85 patients in the Balance group and 82 patients in the control group had
      peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine
      ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group
      compared with controls (0.67 +/- 0.10 versus 0.62 +/- 0.10, P = 0.002). Over the
      2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance
      group but increased significantly in controls [difference -0.004 per month, 95%
      confidence interval (95% CI) -0.005 to -0.002, P < 0.001]. Similar results were
      obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was
      significantly lower in the Balance group than in controls at 3 and 6 months. Over
      the 2-year study period, peritoneal UF increased significantly in the Balance
      group but remained stable in controls (difference 24 mL/day/month, 95% CI 9-39, P
      = 0.002). No differences in peritoneal small solute clearances, prescribed
      dialysate fill volumes or peritoneal glucose exposure were observed between the
      two groups. CONCLUSIONS: Biocompatible and conventional PD solutions exert
      differential effects on peritoneal small solute transport rate and UF over time.
      Adequately powered trials assessing the impact of these differential membrane
      effects on PD technique and patient survival rates are warranted.

PMID- 22859795
TI  - Prognosis of scleroderma renal crisis: a long-term observational study.
AB  - BACKGROUND: Despite the efficacy of angiotensin-converting enzyme (ACE)
      inhibitors, the prognosis of patients with Scleroderma renal crisis (SRC) is
      characterized by a high rate of mortality and progression into end-stage renal
      disease (ESRD). Our aim was to evaluate the prognosis of SRC in our cohort of
      scleroderma patients. METHODS: We reviewed clinical charts of all our patients
      who developed SRC from 1980 to 2005. Outcome measures were ESRD, patients'
      survival and SRC-related mortality. ESRD was defined as the need for chronic
      dialysis; survival was calculated from the time of SRC occurrence by Kaplan-Meier
      method. All patients were treated with ACE inhibitors and 10 patients were also
      treated with plasma exchange (PEx). Indications to PEx were concomitant micro
      angiopathic haemolytic anaemia or intolerance to high doses of ACE inhibitors.
      SPSS package was used for calculation. RESULTS: Of 606 patients, affected with
      systemic sclerosis, who came at our observation during the aforementioned
      interval, 20 (3.3%) developed SRC. One year after SRC onset, 55% of patients
      developed ESRD. The survival rate was 70% at 1 year and 50% at 5 years; the
      mortality rate related to SRC was 35%. Notably, in the subgroup of patients
      treated with PEx, 20% developed ESRD; the survival rate was 90% at 1 year and 70%
      at 5 years; the mortality rate related to SRC was 10%. CONCLUSIONS: Short-term
      prognosis of SRC has improved, but long-term prognosis remains disappointing. PEx
      in addition to ACE inhibitors seems to be a therapeutic option in patients with
      SRC who develop micro-angiopathy or are intolerant to high doses of ACE
      inhibitors.

PMID- 22859797
TI  - Anomalous origin of the right vertebral artery from the right common carotid
      artery associated with an aberrant right subclavian artery.
AB  - Vertebral artery origin anomalies are typically incidental findings during
      angiography or post mortem examination. We present two cases of vertebral origin
      from the right common carotid artery in association with an aberrant right
      subclavian artery. We also review the embryonic development and the clinical
      significance of this anomaly. 

PMID- 22859798
TI  - A 46 year old man with carcinoma of unknown primary site.

PMID- 22859796
TI  - A Phase 2, randomized, partially blinded, active-controlled study assessing the
      efficacy and safety of variable anticoagulation reversal using the REG1 system in
      patients with acute coronary syndromes: results of the RADAR trial.
AB  - AIMS: We sought to determine the degree of anticoagulation reversal required to
      mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent
      ischaemic events in acute coronary syndrome (ACS) patients managed with an early
      invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor
      IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not
      been studied in invasively managed patients with ACS nor has an optimal level of
      reversal allowing safe sheath removal been defined. METHODS AND RESULTS: Non-ST
      elevation ACS patients (n = 640) with planned early cardiac catheterization via
      femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100%
      anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding
      through 30 days. Secondary endpoints included major bleeding and the composite of
      death, myocardial infarction, urgent target vessel revascularization, or
      recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41
      patients. Enrolment was stopped after three patients experienced allergic-like
      reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25,
      50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7,
      and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and
      heparin patients, respectively. CONCLUSION: At least 50% reversal is required to
      allow safe sheath removal after cardiac catheterization. REG1 appears a safe
      strategy to anticoagulate ACS patients managed invasively and warrants further
      investigation in adequately powered clinical trials of patients who require short
      term high-intensity anticoagulation.

PMID- 22859799
TI  - Researchers call for national funding to monitor all birth defects.

PMID- 22859800
TI  - Proposed targets for new NHS commissioners receive lukewarm response.

PMID- 22859801
TI  - Knowledge of Clostridium difficile infection among UK health-care workers:
      development of a knowledge assessment tool.
AB  - Doctors' knowledge provides the basis to support good practice in infection
      prevention and control. However, there exists a paucity of validated knowledge
      assessment tools that can be reliably employed to identify poor knowledge levels
      of Clostridium difficile infection (CDI) within populations of doctors,
      preventing the effective identification of knowledge deficiencies and focused
      targeting of educational interventions. Here, we describe a development process
      to validate a novel CDI knowledge assessment tool for doctors. Two previously
      published CDI knowledge questionnaires were amalgamated to produce a combined
      questionnaire. Content was further evaluated by a panel of CDI experts, producing
      the 'Lothian' questionnaire. These questionnaires were tested in control
      populations comprising either infection control nurse (ICN) specialists or non
      clinically trained individuals, and a cohort of medical staff. We compared the
      efficacy of the 'Lothian' questionnaire against that of previous questionnaire
      reports. We found that all of the questionnaires studied significantly
      discriminated between non-clinical and clinical populations (ICNs and medical
      staff) (P < 0.001) and had similar levels of sensitivity and specificity in
      discrimination between these targeted populations. This study describes the
      development of a robust CDI knowledge assessment tool that can be used to
      evaluate knowledge levels among doctors, compare populations and assist the
      targeting of educational interventions and plot trends following such
      interventions.

PMID- 22859802
TI  - Accuracy of minimal-preparation computerized tomography in the investigation of
      suspected colorectal cancer in frail patients: the experience of Western General
      Hospital, Edinburgh.
AB  - Traditional methods of investigating suspected colorectal carcinoma (CRC) such as
      barium enema, colonoscopy and computerized tomography (CT) pneumocolon are often
      poorly tolerated by frail or elderly patients. Comparatively, minimal-preparation
      CT (MPCT) is a non-invasive investigation that does not require bowel
      preparation. The aim of this study was to review MPCTs carried out at the Western
      General Hospital, Edinburgh, and compare findings with current published data.
      Retrospective analysis of 85 patients (age range 55-99 years) who underwent MPCTs
      at the Western General Hospital between May 2005 and June 2008 was undertaken.
      Results were followed up using clinical notes, pathological and surgical
      databases. Subsequent outcomes were analysed (average follow-up 22 months). The
      prevalence of CRC within the study cohort was 0.14. Sensitivity of MPCT was 1
      (95% confidence interval [CI], 0.69-1) with a specificity of 0.93 (95% CI, 0.84
      0.97). Thirty percent of patients were found to have extracolonic findings
      requiring further investigation or intervention. Of the patients, 4.7% had an
      extracolonic malignancy diagnosed on MPCT. MPCT is a sensitive and specific
      method of investigating CRC in the elderly, infirm or immobile. Our results were
      found to be comparable with that of current published data, validating the
      service provided at the Western General Hospital.

PMID- 22859803
TI  - Views of general practitioners in Grampian about undergraduate psychiatric
      teaching.
AB  - This paper reports the free-text responses of general practitioners (GPs) in the
      Grampian area to a questionnaire about their experiences of undergraduate
      psychiatry teaching. Most respondents were senior GPs whose undergraduate
      training had taken place a number of years ago. Respondents varied in their
      perceptions of the quality of their psychiatric teaching. However, they reported
      common themes such as the bias of undergraduate teaching towards disorders which
      are less relevant to their practice, and the benefits of postgraduate training in
      psychiatry. We suggest that medical schools need to bear the needs of the non
      psychiatrist in mind when developing curricula in psychiatry.

PMID- 22859804
TI  - Paediatric forearm fractures in the west of Scotland.
AB  - Forearm fractures are common paediatric injuries. This study aimed to describe
      the epidemiology and treatment of paediatric forearm fractures in the urban
      population of Glasgow. We reviewed all forearm fractures treated by the
      orthopaedic service in Yorkhill Children's Hospital in 2008 up to the age of 13
      years. Data were gathered from case-notes and radiographs using the prospective
      orthopaedic database to identify patients with forearm fractures. The age, sex,
      side and type of fracture, the timing and mechanism of the injury and treatment
      were documented for the 439 fractures. Census data were used to derive absolute
      age-specific incidences. Distinction was made between torus and other types of
      fractures. Torus fractures require no specific orthopaedic treatment and were
      segregated out. For the remaining 314 fractures, the age and sex distribution,
      seasonal variation of fractures and treatments for each type of fracture were
      examined. The incidence of forearm fractures in our population is 411 fractures
      per 100,000 population per year and 294 fractures per 100,000 population per year
      for non-torus fractures. An increased number of fractures occurred between May
      and August. A fall from less than 1 m was the most common mechanism of injury.
      Sporting injuries were the second most common. This study identifies some
      features which are in agreement with studies from elsewhere in Britain. However,
      there are also interesting differences, such as the Glasgow peak incidence for
      forearm fractures being at age eight, with a marked decline by 12 years.
      Furthermore, our findings have been extended to consideration of type of
      intervention and likelihood of successful treatment.

PMID- 22859805
TI  - Rationalized assessment of prolonged jaundice is safe and cost-effective.
AB  - Prolonged jaundice (PJ) in healthy term neonates is common and frequently benign.
      It can, however, be the earliest manifestation of underlying liver disease. Its
      management requires a balanced approach, avoiding over-investigation of well
      babies while ensuring the early identification of those with pathology. Currently
      marked heterogeneity exists in the assessment of PJ. Over a two-year period we
      prospectively audited the management of PJ in two Level 3 neonatal units prior to
      and after the introduction of a rationalized investigation algorithm in keeping
      with the recently published British Society of Paediatric Gastroenterology,
      Hepatology and Nutrition (BSPGHAN) guidelines (i.e. clinical examination and
      stool inspection combined with measurement of split bilirubin). In this study we
      reviewed initial practice and then evaluated the impact of our change in
      practice. A total of 197 babies, 1.5% of live births, were referred with PJ. Of
      these, 105 babies were included in the first part of the study and 92 babies were
      included in the second part. No pathology relating to PJ, such as infection,
      hepatitis or liver disease, was identified. Following the introduction of our
      rationalized algorithm, we demonstrated a statistically significant reduction in
      the number of return appointments (28 versus 7; P < 0.0009) and repeat
      investigations (37 versus 7; P < 0.0001). This represented a saving of L1575-2625
      per year in laboratory costs alone. Contemporaneously, three infants presented
      with biliary atresia, none of whom were identified by PJ screening and all of
      whom were over seven weeks old at diagnosis. A rationalized approach to the
      assessment of PJ reduces workload and is cost-effective; however, the limitations
      of selective screening, irrespective of how streamlined it is, remain--if babies
      are not identified and referred, they cannot be screened. Population-based
      methodologies offer an alternative approach to the identification of cholestatic
      liver disease and are worthy of further consideration.

PMID- 22859806
TI  - Genetic mutations in patients with possible familial hypercholesterolaemia in
      South East Scotland.
AB  - Familial hypercholesterolaemia (FH) is one of the most common genetic disorders
      in the general population. Genetic testing of this condition is increasingly
      available in the UK to confirm its diagnosis, but the strategies of genetic
      testing vary. In this pilot study, we sought to investigate whether a strategy
      that focuses on the low-density lipoprotein receptor (LDLR) and apolipoprotein B
      (APOB) genes can identify the majority of genetic variants in patients with
      possible FH in South East Scotland. Forty patients with a clinical diagnosis of
      possible FH according to the Simon Broome criteria were recruited in a lipid
      clinic serving South East Scotland. All 18 exons of the LDLR gene were sequenced
      and multiplex ligation probe amplification was performed to identify major
      deletions and duplications. Variants of the APOB gene at codon 3527 were
      investigated by direct sequencing. Genetic mutations were detected in 45% of the
      patients. Sixteen patients (40%) were found to have mutations in their LDLR gene,
      whereas two other patients (5%) were identified as heterozygous for the APOB
      variant commonly associated with FH (c.10580G>A; p.R3527Q). None of these genetic
      variants were detected in more than two patients. Multiple genetic mutations are
      associated with a clinical phenotype of FH in South East Scotland. A genetic
      testing strategy which focuses on a limited number of mutations is unlikely to
      confirm the diagnosis of FH in the majority of patients in this part of Scotland.

PMID- 22859807
TI  - Paediatric head injury admissions over a 10-year period in a regional
      neurosurgical unit.
AB  - Traumatic brain injury is a leading cause of death and disability in childhood. A
      retrospective study of all paediatric head injuries admitted to the neurosurgical
      unit for the West of Scotland over a 10-year period was performed to assess the
      impact of the National Institute for Health and Clinical Excellence head injury
      guidelines on the admission rate and to determine the associated risk factors,
      causes, severity and outcomes of these injuries. There were 564 admissions
      between 1998 and 2007. The median age at presentation was nine years and two
      months. There was no change in the admission rate, injury mechanism or severity
      of head injury admitted over the period studied. A relationship was observed
      between the Scottish Index of Multiple Deprivation Score and the incidence of
      head injury (P = 0.05). Alcohol was reported as a causative factor in only a
      small number of cases, and moderate to severe head injuries were more commonly
      identified as a result of road traffic accidents.

PMID- 22859808
TI  - Current management options for the small renal mass in a solitary kidney.
AB  - The widespread use of cross-sectional imaging has resulted in an increase in the
      frequency of incidentally identified small renal masses (SRMs). With high cancer
      specific survival rates following radical nephrectomy, there is an increasing
      patient cohort at risk of developing a metachronous contralateral tumour. Nephron
      sparing surgery (NSS) has been shown to reduce progression of chronic kidney
      disease, being the impetus to utilize NSS for the management of SRMs in an
      anatomical or functional solitary kidney. At present, open partial nephrectomy is
      the gold standard treatment for an SRM in a solitary kidney; however, there are a
      number of other minimally invasive options, including laparoscopic partial
      nephrectomy, and in situ ablative procedures. In addition, variables such as warm
      and cold ischaemia and renal vascular clamping have been shown to affect
      outcomes. In this review, we summarize contemporary management options focusing
      specifically on oncological and functional outcomes.

PMID- 22859810
TI  - Unnecessary diagnostic investigations in benign acute childhood myositis: a case
      series report.
AB  - Benign acute childhood myositis (BACM) is a rare, acute, self-limiting muscle
      disorder, mainly affecting school-aged boys, with an excellent prognosis,
      requiring no therapeutic intervention. We report a series of seven previously
      healthy school-aged children with clinical and laboratory findings suggesting
      BACM where no specific diagnostic investigations were performed. All of the
      children were hospitalized without any specific therapeutic intervention and were
      discharged after two or three days free of symptoms, residual impairment or other
      complication. This report emphasizes that the correct diagnosis of BACM, by
      considering the characteristic clinical and laboratory findings of this syndrome
      and by recognizing more severe pathological conditions, which must be excluded
      from the diagnosis, can prevent unnecessary diagnostic investigations and
      reassure both parents and patients of the excellent prognosis.

PMID- 22859811
TI  - Vertebral erosion resulting from a 'non-ruptured' abdominal aortic aneurysm: case
      report and literature review.
AB  - The natural history of abdominal aortic aneurysms (AAAs) renders them clinically
      silent for much of their evolution. These aneurysms will inevitably expand with
      time and, although surveillance programmes exist, an acutely ruptured AAA is
      still a relatively common clinical scenario. The classical presentation is with
      rapid haemodynamic deterioration with accompanying severe abdominal or back pain.
      Less commonly, patients may present with a stable haemodynamic profile and vague
      symptomatology; they are usually found to have a chronic contained rupture with a
      defect in the vascular wall with co-existent pseudoaneurysm and retroperitoneal
      haematoma formation. We report a rare case of AAA with posterior wall defect and
      erosion into the vertebral body with no accompanying pseudoaneurysm or haematoma
      and discuss the clinical implications of such a presentation.

PMID- 22859812
TI  - Legionella pneumophila serogroup 3 infection: importance of serology.
AB  - We present a case of Legionella pneumophila serogroup 3 (LP3) infection in a
      patient with severe community-acquired pneumonia (CAP). The diagnosis was
      complicated by an initial equivocal L. pneumophila urinary antigen test, followed
      by two negative samples. LP3 was cultured from a sputum sample and the diagnosis
      was confirmed by serology 15 days into the admission. This case highlights the
      importance of considering non-LP1 serogroups as causes of CAP and the role of
      serological testing in diagnosis.

PMID- 22859813
TI  - Not hysteria: ovarian teratoma-associated anti-N-methyl-D-aspartate receptor
      encephalitis.
AB  - We report a case of a 33-year-old nulliparous woman who, following a short
      prodromal illness, experienced a series of psychiatric and behavioural symptoms.
      These included states of terror, insomnia, delirium, self-harm and suicidal
      ideation, facial dyskinesias, verbigeration, cognitive impairment, reduced
      responsiveness, violence and paranoia. A diagnosis of anti-N-methyl-d-aspartate
      (NMDAR) encephalitis was made 50 days after symptom onset. Early tumour removal
      is associated with an improved prognosis and a laparoscopic oophorectomy was
      performed following detection of a dermoid cyst. Within 24 hours of the operation
      there was marked improvement in cognitive function and appetite.

PMID- 22859814
TI  - Infusion of noradrenaline through the proximal line of a migrated central venous
      catheter.
AB  - A 41-year-old, obese, patient was admitted to Accident and Emergency with a
      history of leg cellulitis. A central line was inserted. Documented aspiration of
      blood from all lines, central venous pressure trace obtained and correct position
      noted on the chest X-ray (CXR). The patient became increasingly septic despite
      antibiotic therapy. He was subsequently commenced on a noradrenaline infusion;
      however, the blood pressure was unresponsive. On admission to the intensive care
      unit (ICU), it was noted he had an area of white skin over the right clavicle.
      The infusions were stopped and a CXR confirmed proximal migration of the line.
      The central line was re-sited and his noradrenaline recommenced with an
      improvement in his blood pressure. Acute renal failure developed which required
      haemofiltration for 24 hours. The condition improved and the patient was
      discharged from ICU. It took several weeks for his renal function to return to
      normal, but he was discharged home with no permanent damage.

PMID- 22859815
TI  - Lateral condyle fracture of a child's humerus: the radiographic features may be
      subtle.
AB  - Fractures of the lateral condyle of the humerus in children are relatively common
      and can be easily missed on initial plain radiographs especially in the younger
      age group. We present a case in which diagnosis of this fracture was delayed for
      five weeks and therefore presented more challenging surgical management. The
      salient features that were apparent on the initial radiograph at presentation are
      discussed as is the use of further imaging techniques that may help to clarify
      the initial diagnosis. This could significantly reduce the risk of serious
      complications such as chronic pain, deformity and nerve palsy.

PMID- 22859816
TI  - Severe and complicated Plasmodium vivax malaria in children.
AB  - Plasmodium vivax, thought to be benign until recently, has been associated with
      severe malaria and its complications. This retrospective study describes severe
      and complicated P. vivax malaria in children. It affected almost all of the organ
      systems and the most commonly found complications were thrombocytopenia and
      severe anaemia. All children with malaria, including malaria caused by P. vivax,
      should be monitored for such complications.

PMID- 22859817
TI  - A 200-second quasi-periodicity after the tidal disruption of a star by a dormant
      black hole.
AB  - Supermassive black holes (SMBHs; mass is greater than or approximately 10(5)
      times that of the Sun) are known to exist at the center of most galaxies with
      sufficient stellar mass. In the local universe, it is possible to infer their
      properties from the surrounding stars or gas. However, at high redshifts we
      require active, continuous accretion to infer the presence of the SMBHs, which
      often comes in the form of long-term accretion in active galactic nuclei. SMBHs
      can also capture and tidally disrupt stars orbiting nearby, resulting in bright
      flares from otherwise quiescent black holes. Here, we report on a ~200-second x
      ray quasi-periodicity around a previously dormant SMBH located in the center of a
      galaxy at redshift z = 0.3534. This result may open the possibility of probing
      general relativity beyond our local universe.

PMID- 22859818
TI  - Conduction of ultracold fermions through a mesoscopic channel.
AB  - In a mesoscopic conductor, electric resistance is detected even if the device is
      defect-free. We engineered and studied a cold-atom analog of a mesoscopic
      conductor. It consists of a narrow channel connecting two macroscopic reservoirs
      of fermions that can be switched from ballistic to diffusive. We induced a
      current through the channel and found ohmic conduction, even when the channel is
      ballistic. We measured in situ the density variations resulting from the presence
      of a current and observed that density remains uniform and constant inside the
      ballistic channel. In contrast, for the diffusive case with disorder, we observed
      a density gradient extending through the channel. Our approach opens the way
      toward quantum simulation of mesoscopic devices with quantum gases.

PMID- 22859819
TI  - Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus
      neurons.
AB  - Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day
      night cycle. They are orchestrated by a central circadian clock in the brain, the
      suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to
      metabolic changes in reduction and oxidation (redox); however, circadian cycles
      in protein oxidation have been reported in anucleate cells, where no
      transcription occurs. We investigated whether the SCN also expresses redox cycles
      and how such metabolic oscillations might affect neuronal physiology. We detected
      self-sustained circadian rhythms of SCN redox state that required the molecular
      clockwork. The redox oscillation could determine the excitability of SCN neurons
      through nontranscriptional modulation of multiple potassium (K(+)) channels.
      Thus, dynamic regulation of SCN excitability appears to be closely tied to
      metabolism that engages the clockwork machinery.

PMID- 22859820
TI  - Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans.
AB  - The synaptic adhesion molecules neurexin and neuroligin alter the development and
      function of synapses and are linked to autism in humans. Here, we found that
      Caenorhabditis elegans neurexin (NRX-1) and neuroligin (NLG-1) mediated a
      retrograde synaptic signal that inhibited neurotransmitter release at
      neuromuscular junctions. Retrograde signaling was induced in mutants lacking a
      muscle microRNA (miR-1) and was blocked in mutants lacking NLG-1 or NRX-1.
      Release was rapid and abbreviated when the retrograde signal was on, whereas
      release was slow and prolonged when retrograde signaling was blocked. The
      retrograde signal adjusted release kinetics by inhibiting exocytosis of synaptic
      vesicles (SVs) that are distal to the site of calcium entry. Inhibition of
      release was mediated by increased presynaptic levels of tomosyn, an inhibitor of
      SV fusion.

PMID- 22859822
TI  - Comment on "phenotypic analysis of pneumococcal polysaccharide-specific B cells".

PMID- 22859821
TI  - Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited
      ISG15 deficiency.
AB  - ISG15 is an interferon (IFN)-alpha/beta-inducible, ubiquitin-like intracellular
      protein. Its conjugation to various proteins (ISGylation) contributes to
      antiviral immunity in mice. Here, we describe human patients with inherited ISG15
      deficiency and mycobacterial, but not viral, diseases. The lack of intracellular
      ISG15 production and protein ISGylation was not associated with cellular
      susceptibility to any viruses that we tested, consistent with the lack of viral
      diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15
      secretion by leukocytes-granulocyte, in particular-reduced the production of IFN
      gamma by lymphocytes, including natural killer cells, probably accounting for the
      enhanced susceptibility to mycobacterial disease. This experiment of nature shows
      that human ISGylation is largely redundant for antiviral immunity, but that ISG15
      plays an essential role as an IFN-gamma-inducing secreted molecule for optimal
      antimycobacterial immunity.

PMID- 22859823
TI  - Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia.
AB  - Inactivating mutations in the Staphylococcus aureus virulence regulator agr are
      associated with worse outcomes in bacteremic patients. However, whether agr
      dysfunction is primarily a cause or a consequence of early bacteremia is unknown.
      Analysis of 158 paired S. aureus clones from blood and nasal carriage sites in
      individual patients revealed that recovery of an agr-defective mutant from blood
      was usually predicted by the agr functionality of carriage isolates. Many agr
      positive blood isolates produced low levels of hemolytic toxins, but levels were
      similar to those of colonizing strains within patients, suggesting that
      introduction into the blood did not select for mutations with minor functional
      effects. Evidently, the transition from commensalism to opportunism in S. aureus
      does not require full virulence in hospitalized patients. Furthermore, agr
      defective mutants were found in uninfected nasal carriers in the same proportion
      as in carriers who develop bacteremia, suggesting low correlation between
      virulence and infectivity.

PMID- 22859824
TI  - Ixodes scapularis JAK-STAT pathway regulates tick antimicrobial peptides, thereby
      controlling the agent of human granulocytic anaplasmosis.
AB  - Ixodes scapularis transmits the agent of human granulocytic anaplasmosis, among
      other pathogens. The mechanisms used by the tick to control Anaplasma
      phagocytophilum are not known. We demonstrate that the I. scapularis Janus kinase
      (JAK)-signaling transducer activator of transcription (STAT) pathway plays a
      critical role in A. phagocytophilum infection of ticks. The A. phagocytophilum
      burden increases in salivary glands and hemolymph when the JAK-STAT pathway is
      suppressed by RNA interference. The JAK-STAT pathway exerts its anti-Anaplasma
      activity presumably through STAT-regulated effectors. A salivary gland gene
      family encoding 5.3-kDa antimicrobial peptides is highly induced upon A.
      phagocytophilum infection of tick salivary glands. Gene expression and
      electrophoretic mobility shift assays showed that the 5.3-kDa antimicrobial
      peptide-encoding genes are regulated by tick STAT. Silencing of these genes
      increased A. phagocytophilum infection of tick salivary glands and transmission
      to mammalian host. These data suggest that the JAK-STAT signaling pathway plays a
      key role in controlling A. phagocytophilum infection in ticks by regulating the
      expression of antimicrobial peptides.

PMID- 22859826
TI  - A large, population-based study of 2009 pandemic Influenza A virus subtype H1N1
      infection diagnosis during pregnancy and outcomes for mothers and neonates.
AB  - BACKGROUND: Pregnant women were at increased risk for serious outcomes of 2009
      pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but
      little is known about the overall impact of the pandemic on neonatal and maternal
      outcomes. METHODS: We identified live births that occurred from 1 July 2008
      through 31 May 2010 in 5 Kaiser Permanente regions. Pregnant women were
      considered to have influenza if they had a positive result of a laboratory test
      for influenza virus or if they received a diagnosis of influenza during a period
      in which seasonal influenza virus or A(H1N1)pdm09 was the predominant circulating
      virus. RESULTS: There were 111 158 births from 109 015 pregnancies involving 107
      889 mothers; 368 pregnant women (0.3%) received a diagnosis of influenza due to
      seasonal virus, and 959 (0.9%) received a diagnosis of influenza due to
      A(H1N1)pdm09; 107 688 did not receive an influenza diagnosis. Pregnant women with
      influenza due to A(H1N1)pdm09 were more likely than women with seasonal influenza
      infection to be hospitalized within 30 days of the diagnosis (27% vs 12%; odds
      ratio [OR], 2.84 [95% confidence interval {CI}, 2.01-4.02]). Pregnant women with
      A(H1N1)pdm09 who started antiviral treatment >=2 days after the diagnosis were
      significantly more likely to be hospitalized than those who started antiviral
      treatment <2 days after diagnosis (OR, 3.43 [95% CI, 1.55-7.56]). Mothers with
      seasonal influenza virus infection had an increased risk for having a small-for
      gestational-age infant (OR, 1.59 [95% CI, 1.15-2.20]). CONCLUSIONS: In this
      large, geographically diverse population, A(H1N1)pdm09 infection increased the
      risk for hospitalization during pregnancy. Late initiation of antiviral treatment
      was also associated with an increased risk for hospitalization.

PMID- 22859825
TI  - Humoral, mucosal, and cell-mediated immunity against vaccine and nonvaccine
      genotypes after administration of quadrivalent human papillomavirus vaccine to
      HIV-infected children.
AB  - OBJECTIVES: To characterize the immunogenicity of a quadrivalent human
      papillomavirus vaccine (QHPV) in human immunodeficiency virus (HIV)-infected
      children, we studied their immune responses to 3 or 4 doses. METHODS: HIV
      infected children aged 7-12 years with a CD4 cell percentage of >=15% of
      lymphocytes, received 3 doses of QHPV with or without a fourth dose after 72
      weeks. Type-specific and cross-reactive antibodies and cell-mediated immunity
      were measured. RESULTS: Type-specific antibodies to HPV6, 11, and 16 were
      detected in 100% and >=94% of children at 4 and 72 weeks, respectively, after the
      third QHPV dose. Corresponding numbers for HPV18 were 97% and 76%, respectively.
      A fourth QHPV dose increased seropositivity to >=96% for all vaccine genotypes.
      Four weeks after the third QHPV dose, 67% of vaccinees seroconverted to HPV31, an
      HPV16-related genotype not in the vaccine; 69% and 39% of vaccinees developed
      mucosal HPV16 and 18 immunoglobulin G antibodies, respectively; and 60% and 52%
      of vaccinees developed cytotoxic T lymphocytes (CTLs) for HPV16 and 31,
      respectively. CONCLUSIONS: Three QHPV doses generated robust and persistent
      antibodies to HPV6, 11, and 16 but comparatively weaker responses to HPV18. A
      fourth dose increased antibodies against all vaccine genotypes in an anamnestic
      fashion. CTLs and mucosal antibodies against vaccine genotypes, as well as cross
      reactive antibodies and CTL against nonvaccine genotypes, were detected.

PMID- 22859827
TI  - Everolimus for advanced pancreatic neuroendocrine tumours: a subgroup analysis
      evaluating Japanese patients in the RADIANT-3 trial.
AB  - OBJECTIVE: Everolimus, an inhibitor of the mammalian target of rapamycin, has
      recently demonstrated efficacy and safety in a Phase III, double-blind,
      randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade
      advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4
      fold improvement compared with placebo in progression-free survival, representing
      a 65% risk reduction for progression. The purpose of this analysis was to
      investigate the efficacy and safety of everolimus in the Japanese subgroup
      enrolled in the RADIANT-3 study. METHODS: Subgroup analysis of the Japanese
      patients was performed comparing efficacy and safety between everolimus 10 mg/day
      orally (n = 23) and matching placebo (n = 17). The primary endpoint was
      progression-free survival. Safety was evaluated on the basis of the incidence of
      adverse drug reactions. RESULTS: Progression-free survival was significantly
      prolonged with everolimus compared with placebo. The median progression-free
      survival was 19.45 months (95% confidence interval, 8.31-not available) with
      everolimus vs 2.83 months (95% confidence interval, 2.46-8.34) with placebo,
      resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95%
      confidence interval, 0.08-0.48; P< 0.001). Adverse drug reactions occurred in all
      23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients
      receiving placebo; most were grade 1/2 in severity. The most common adverse drug
      reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17;
      74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10;
      44%) and pneumonitis (n = 10; 44%). CONCLUSIONS: These results support the use of
      everolimus as a valuable treatment option for Japanese patients with advanced
      pancreatic neuroendocrine tumours.

PMID- 22859828
TI  - Association of coping style, cognitive errors and cancer-related variables with
      depression in women treated for breast cancer.
AB  - OBJECTIVE: The purpose of this study was to examine the correlation between
      depression levels with coping styles and cognitive errors in women treated for
      breast cancer. METHODS: A total of 110 breast cancer outpatients who had had
      surgery at least 6 months previously, had completed adjuvant cancer treatment and
      had not experienced metastasis or recurrent lesions were evaluated. The Automatic
      Thoughts Questionnaire, Cognitive Errors Questionnaire, Mental Adjustment to
      Cancer Scale and Beck Depression Inventory were administered to all patients.
      Semi-structured interview forms were used to obtain medical and demographic data.
      All patients were categorized into depression and non-depression groups according
      to their Beck Depression Inventory scores. The study protocol was approved by the
      Medical Ethics Committee of Istanbul University Oncology Institute. RESULTS:
      Higher cognitive errors and automatic thought scores were found in the depression
      group. Fighting spirit was found to be the primary coping style used in the non
      depression group, while helplessness/hopelessness, anxious/preoccupation and
      fatalism were the coping styles used the most in the depression group. No
      association between depression and socio-demographic (except for educational
      level) and cancer-related variables was detected. However, it was found that
      automatic thoughts, cognitive errors, education level, fighting spirit and
      anxious/preoccupation are important indicators of depression in our sample.
      CONCLUSIONS: A causal relationship exists between depression and a patient's
      cognitive patterns and accompanying anxiety. The degree of depression is
      inversely related to both fighting spirit coping type and educational level. If
      clinicians take this into consideration, diagnosing and treating depression will
      be more effective.

PMID- 22859829
TI  - Molecular mechanisms of spontaneous and directed mast cell motility.
AB  - Migration is a fundamental function of immune cells, and a role for Ca(2+) in
      immune cell migration has been an interest of scientific investigations for many
      decades. Mast cells are the major effector cells in IgE-mediated immune
      responses, and cross-linking of IgE-FcepsilonRI complexes at the mast cell
      surface by antigen activates a signaling cascade that causes mast cell
      activation, resulting in Ca(2+) mobilization and granule exocytosis. These cells
      are known to accumulate at sites of inflammation in response to parasite and
      bacterial infections. Using real-time imaging, we monitored chemotactic migration
      of RBL and rat BMMCs in response to a gradient of soluble multivalent antigen.
      Here, we show that Ca(2+) influx via Orai1 plays an important role in regulating
      spontaneous motility and directional migration of mast cells toward antigen via
      IgER complexes. Inhibition of Ca(2+) influx or knockdown of the Ca(2+) entry
      channel protein Orai1 by shRNA causes inhibition of both of these processes. In
      addition, a mutant Syk- shows impaired spontaneous motility and chemotaxis toward
      antigen that is rescued by expression of Syk. Our findings identify a novel
      Ca(2+) influx-mediated, Orai1-dependent mechanism for mast cell migration.

PMID- 22859830
TI  - Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid
      derived cells slows resolution of inflammation and infection.
AB  - The absence or reduction of CFTR function causes CF and results in a pulmonary
      milieu characterized by bacterial colonization and unresolved inflammation. The
      ineffectiveness at controlling infection by species such as Pseudomonas
      aeruginosa suggests defects in innate immunity. Macrophages, neutrophils, and DCs
      have all been shown to express CFTR mRNA but at low levels, raising the question
      of whether CFTR has a functional role in these cells. Bone marrow transplants
      between CF and non-CF mice suggest that these cells are inherently different; we
      confirm this observation using conditional inactivation of Cftr in myeloid
      derived cells. Mice lacking Cftr in myeloid cells overtly appear
      indistinguishable from non-CF mice until challenged with bacteria instilled into
      the lungs and airways, at which point, they display survival and inflammatory
      profiles intermediate in severity as compared with CF mice. These studies
      demonstrate that Cftr is involved directly in myeloid cell function and imply
      that these cells contribute to the pathophysiological phenotype of the CF lung.

PMID- 22859832
TI  - Redox control of NLRP3 inflammasome activation in health and disease.
AB  - Shifts in the redox balance between ROS and antioxidants regulate innate immunity
      at various levels. Changes in the redox microenvironment modulate the activation
      potential of the NLRP3 inflammasome, a signaling platform that activates caspase
      1, allowing the maturation of IL-1beta. However, a clear definition of the
      underlying mechanism is missing. In this essay, I review the most-credited
      theories on inflammasome activation. In particular, I will focus on the redox
      mediated mechanisms that regulate the assembly of NLRP3 inflammasome and discuss
      how aberrations in them are implicated in the pathogenesis of autoinflammatory
      diseases.

PMID- 22859833
TI  - Dimitrios Oreopoulos: fondly remembered and greatly missed.

PMID- 22859831
TI  - E-prostanoid 2 receptors dampen mast cell degranulation via cAMP/PKA-mediated
      suppression of IgE-dependent signaling.
AB  - The experimental administration of PGE(2) for the treatment of asthma dampens
      clinical symptoms, and similar efficacy has been found in dust mite-induced
      hypersensitivity reactions in animal models. Here, we investigate the mechanism
      by which PGE(2) mediates suppression of MC degranulation. We find that the effect
      of PGE(2) on FcepsilonRI-dependent MC degranulation varies from activating to
      suppressing, depending on the relative ratio of EP(2) to EP(3) expression on
      these cells with suppression evident only in cells having increased EP(2) to
      EP(3) expression. Consistent with a role for EP(2) in suppressing MC responses in
      vitro, we found that a selective EP(2) agonist, Butaprost, inhibited MC-mediated
      FcepsilonRI-induced immediate hypersensitivity in a model of PCA. EP(2)
      engagement on MCs increased cAMP production and inhibited FcepsilonRI-mediated
      calcium influx. In addition, it also decreased the extent of FcepsilonRI-induced
      Fyn kinase activity, leading to decreased phosphorylation of key signaling
      molecules such as Gab2 and Akt. Treatment with an antagonist of cAMP or shRNA
      down-regulation of PKA (the principal intracellular target of cAMP) reversed the
      EP(2)-mediated inhibitory effect on MC degranulation and restored calcium influx
      and phosphorylation of Akt. Collectively, the findings demonstrate that EP(2)
      suppresses the Fyn-mediated signals that are central to FcepsilonRI-dependent MC
      degranulation, suggesting that engagement of the EP(2) on MCs may be beneficial
      in dampening allergic responses.

PMID- 22859834
TI  - Dimitrios Oreopoulos 24 May 1936 - 25 April 2012.

PMID- 22859835
TI  - Reflections of Dimitrios G. Oreopoulos: mentor, advisor, and friend.

PMID- 22859837
TI  - Renal replacement therapy in congestive heart failure requiring left ventricular
      assist device augmentation.
AB  - "Cardiorenal syndrome" is a term used to describe a dys-regulation of the heart
      affecting the kidneys, or vice versa, in an acute or chronic manner (1,2). Renal
      impairment can range from reversible ischemic damage to renal failure requiring
      short- or long-term renal replacement therapy (2). Patients who require
      mechanical circulatory support, such as a left ventricular assist device (LVAD),
      as definitive treatment for congestive heart failure or as a bridge to cardiac
      transplantation pose a unique challenge with respect to receiving dialysis,
      because they experience higher rates of morbidity and mortality from infection in
      the post-LVAD period (3-7). Acute dialysis access can pose an increased infection
      risk. In this article, we present a patient who required renal replacement
      therapy and a LVAD for management of acute-on-chronic cardiorenal syndrome while
      awaiting heart transplantation. A literature review to determine whether
      peritoneal dialysis or hemodialysis is superior for patients with profound
      hemodynamic dysfunction and the need to minimize risk of infection did not offer
      clear guidance about which modality is superior in patients with advanced
      congestive heart failure. However, there is clear evidence of the superiority of
      peritoneal dialysis in reducing the risk of systemic infection secondary to acute
      dialysis access. Given the high risk of LVAD infection, we therefore conclude
      that, to decrease mortality secondary to systemic infection, peritoneal dialysis
      should strongly be considered in patients who require renal replacement therapy
      before or after LVAD placement.

PMID- 22859838
TI  - Peritoneal dialysis and the pediatric patient.

PMID- 22859839
TI  - Learning from the children.

PMID- 22859842
TI  - Peritoneal dialysis in children with acute kidney injury: a developing country
      experience.
AB  - BACKGROUND: Peritoneal dialysis (PD) is the preferred and convenient treatment
      modality for acute kidney injury (AKI) in children and hemodynamically unstable
      patients. METHODS: The outcome of acute PD was studied in 57 children (39 boys)
      with AKI, aged 1 month to 12 years, at a tertiary care center of a teaching
      hospital in India. RESULTS: Hemolytic uremic syndrome (36.8%) was the most common
      cause of AKI, followed by septicemia (24.6%) and acute tubular necrosis (19.3%).
      Treatment with PD was highly effective in lowering retention markers (p < 0.001).
      Overall mortality was 36.8%. The risk of mortality by multi-variate analysis was
      higher when patients were anuric [odds ratio (OR): 8.2; 95% confidence interval
      (CI): 1.3 to 49; p < 0.05], had septicemia (OR: 3.79; 95% CI: 1.55 to 25.8; p <
      0.05), or severe infectious complications (OR: 8.2; 95% CI: 1.5 to 42.9; p <
      001). CONCLUSIONS: Because of its simplicity and feasibility, acute PD is still
      an appropriate treatment choice for children with AKI in resource-poor settings.
      Septicemia and severity of AKI are contributory factors to high mortality in
      pediatric acute kidney injury.

PMID- 22859840
TI  - Impact of global economic disparities on practices and outcomes of chronic
      peritoneal dialysis in children: insights from the International Pediatric
      Peritoneal Dialysis Network Registry.
AB  - BACKGROUND, OBJECTIVES, AND METHODS: The number of patients on chronic peritoneal
      dialysis (CPD) is increasing rapidly on a global scale. We analyzed the
      International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global
      database active in 33 countries spanning a wide range in gross national income
      (GNI), to identify the impact of economic conditions on CPD practices and
      outcomes in children and adolescents. RESULTS: We observed close associations of
      GNI with the fraction of very young patients on dialysis, the presence and number
      of comorbidities, the prevalence of patients with unexplained causes of end-stage
      kidney disease, and the rate of culture-negative peritonitis. The prevalence of
      automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The
      GNI stratum also affected the use of biocompatible peritoneal dialysis fluids,
      enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs,
      and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly
      affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to
      5.5) independently of young patient age and the number of comorbidities present.
      Patients from low-income countries tended to die more often from infections
      unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong
      independent predictor of standardized height (p < 0.0001), adding to the impact
      of congenital renal disease, anuria, age at PD start, and dialysis vintage.
      Patients from the lower economic strata (GNI < $18 000) had higher serum
      parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin
      concentrations. No impact of GNI was observed with regard to CPD technique
      survival or peritonitis incidence. CONCLUSIONS: We conclude that CPD is practiced
      successfully, albeit with major regional variation related to economic
      differences, in children around the globe. The variations encompass the
      acceptance of very young patients and those with associated comorbidities to
      chronic dialysis programs, the use of automated PD and expensive drugs, and the
      diagnostic management of peritonitis. These variations in practice related to
      economic difference do not appear to affect PD technique survival; however,
      economic conditions seem to affect mortality on dialysis and standardized height,
      a marker of global child morbidity.

PMID- 22859843
TI  - The influence of duration of peritoneal dialysis therapy on the outcomes of
      initial and subsequent peritonitis is different.

PMID- 22859841
TI  - Comorbidities in chronic pediatric peritoneal dialysis patients: a report of the
      International Pediatric Peritoneal Dialysis Network.
AB  - BACKGROUND, OBJECTIVES, AND METHODS: Hospitalization and mortality rates in
      pediatric dialysis patients remain unacceptably high. Although studies have
      associated the presence of comorbidities with an increased risk for death in a
      relatively small number of pediatric dialysis patients, no large-scale study had
      set out to describe the comorbidities seen in pediatric dialysis patients or to
      evaluate the impact of those comorbidities on outcomes beyond the newborn period.
      In the present study, we evaluated the prevalence of comorbidities in a large
      international cohort of pediatric chronic peritoneal dialysis (CPD) patients from
      the International Pediatric Peritoneal Dialysis Network registry and began to
      assess potential associations between those comorbidities and hospitalization
      rates and mortality. RESULTS: Information on comorbidities was available for 1830
      patients 0 - 19 years of age at dialysis initiation. Median age at dialysis
      initiation was 9.1 years [interquartile range (IQR): 10.9], median follow-up for
      calculation of hospitalization rates was 15.2 months (range: 0.2 - 80.9 months),
      and total follow-up time in the registry was 2095 patient-years. At least 1
      comorbidity had been reported for 602 of the patients (32.9%), with 283 (15.5%)
      having cognitive impairment; 230 (12.6%), motor impairment; 167 (9.1%), cardiac
      abnormality; 76 (4.2%), pulmonary abnormality; 212 (11.6%), ocular abnormality;
      and 101 (5.5%), hearing impairment. Of the 150 patients (8.2%) that had a defined
      syndrome, 85% had at least 1 nonrenal comorbidity, and 64% had multiple
      comorbidities. The presence of at least 1 comorbidity was associated with a
      higher hospitalization rate [hospital days per 100 observation days: 1.7 (IQR:
      5.8) vs 1.2 (IQR: 3.9), p = 0.001] and decreased patient survival (4-year
      survival rate: 73% vs 90%, p < 0.0001). CONCLUSIONS: Nearly one third of
      pediatric CPD patients in a large international cohort had at least 1
      comorbidity, and multiple comorbidities were frequently reported among patients
      with a defined syndrome. Preliminary analysis suggests an association between
      comorbidity and poor outcome in those patients. As this powerful international
      registry matures, further multivariate analyses will be important to more clearly
      define the impact of comorbidities on hospitalization rates and mortality in
      pediatric CPD patients.

PMID- 22859844
TI  - Improvement in culture-negative peritoneal dialysis-related peritonitis: a single
      center's experience.

PMID- 22859845
TI  - Mucormycosis--a possible trigger pathogen for encapsulating peritoneal sclerosis.

PMID- 22859846
TI  - Peritoneal-uterine communication: a complication of prolonged embedding of a
      peritoneal catheter.

PMID- 22859847
TI  - Peritoneal dialysis-related peritonitis caused by erosion of umbilical abscess
      into the peritoneal cavity.

PMID- 22859848
TI  - The role of collagen arrangement change during tendon healing demonstrated by
      scanning electron microscopy.
AB  - The dry weight of tendon tissue is accounted for mainly by collagen fibers.
      Accordingly, the tendon-healing process primarily involves repair of collagen
      fibers. During the remodeling phase of tendon healing, newly proliferating
      collagen fibers are transformed into a mature repaired tendon. Despite the
      importance of this phenomenon, the details of fibrous rebuilding have not been
      reported previously. The aim of this study was to visualize the ultrastructural
      changes and to obtain a clear understanding of the reorganization of the collagen
      fibers in the tendon repair site, using rat Achilles tendons. We used scanning
      electron microscopy (SEM) with cell maceration as the main method of analysis.
      Pretreatment with cell maceration removed the cellular components successfully.
      This allowed precise visualization of each collagen fiber and the three
      dimensional network of the fibers. This study was the first to apply the cell
      maceration/SEM method to observe tendon tissue. Seven days after surgery, new
      collagen fibers grew extensively in the repair site in a random arrangement.
      Fourteen days after surgery, the collagen fibers began to form an axial
      arrangement. Near the tendon stump, this change progressed from the outer layer
      to the core region. On the other hand, in the middle of the repair site, it
      progressed from the core to the outer layer. Change in the axial arrangement of
      collagen fibers contributes to the connection between the repair site and the
      tendon stump and to the separation of the repair site from the paratenon.

PMID- 22859849
TI  - Multiplicities in cancer research: ubiquitous and necessary evils.
AB  - Scientific inquiry involves observations and measurements, some of which are
      planned and some of which are not. The most interesting or unusual observations
      might be regarded as discoveries and therefore particularly worthy of
      publication. However, the observational process is fraught with inferential land
      mines, especially if the discoveries are serendipitous. Multiple observations
      increase the probability of false-positive conclusions and have led to many false
      and otherwise misleading publications. Statisticians recommend adjustments to
      final inferences with the goal of reducing the rate of false positives, a
      strategy that increases the rate of false negatives. Some scientists object to
      making such adjustments, arguing that it should not be more difficult to
      determine the validity of a discovery simply because other observations were
      made. Which tack is right? How does one decide that any particular scientific
      discovery is real? Unfortunately, there is no panacea, no one-size-fits-all
      approach. The goal of this commentary is to elucidate the issues and provide
      recommendations for conducting and reporting results of empirical studies, with
      emphasis on the problems of multiple comparisons and other types of
      multiplicities, including what I call "silent multiplicities." Because of the
      many observations, outcomes, subsets, treatments, etc, that are typically made or
      addressed in epidemiology and biomarker research, these recommendations may be
      particularly relevant for such studies. However, the lessons apply quite
      generally. I consider both frequentist and Bayesian statistical approaches.

PMID- 22859850
TI  - Biomarkers of phenethyl isothiocyanate-mediated mammary cancer chemoprevention in
      a clinically relevant mouse model.
AB  - BACKGROUND: Phenethyl isothiocyanate (PEITC) is a natural plant compound with
      chemopreventative potential against some cancers and the ability to induce
      apoptosis in breast cancer cells. METHODS: Female mouse mammary tumor virus-neu
      mice were fed a control AIN-76A diet (n = 35) or the same diet supplemented with
      3 umol PEITC/g diet (n = 33) for 29 weeks, at which time they were killed. Breast
      tissue sections were stained with hematoxylin and eosin for histopathological
      assessments, and incidence and size of macroscopic mammary tumors were assessed.
      Cell proliferation (Ki-67 staining), apoptosis (terminal deoxynucleotidyl
      transferase-mediated dUTP nick-labeling), and neoangiogenesis (CD31 staining)
      were determined in tumor sections. Plasma levels of transthyretin were measured
      in treated and control mice. Expression of proteins in mammary tumor sections was
      determined by immunohistochemistry. Proteomic profiling was performed by two
      dimensional gel electrophoresis followed by mass spectrometry. All statistical
      tests were two-sided. RESULTS: Administration of PEITC for 29 weeks was
      associated with 53.13% decreased incidence of macroscopic mammary tumors (mean
      tumor incidence, PEITC-supplemented diet vs control diet, 18.75% vs 40.00%,
      difference = -21.25%, 95% confidence interval [CI] = -43.19% to 0.69%, P = .07)
      and with a 56.25% reduction in microscopic mammary carcinoma lesions greater than
      2 mm(2) (mean incidence, PEITC-supplemented diet vs control diet, 18.75% vs
      42.86%, difference = -24.11%, 95% CI = -46.35% to -1.86%, P = .04). PEITC
      mediated mammary cancer growth inhibition was not because of suppression of human
      epidermal growth factor receptor-2 expression but was associated with reduced
      cellular proliferation and neoangiogenesis, increased apoptosis, and altered
      expression of several proteins, including decreased ATP synthase in the tumor and
      increased plasma levels of transthyretin. CONCLUSIONS: PEITC inhibits the growth
      of mammary cancers in a mouse model with similarities to human breast cancer
      progression. ATP synthase and transthyretin appear to be novel biomarkers
      associated with PEITC exposure.

PMID- 22859851
TI  - Npt2b deletion attenuates hyperphosphatemia associated with CKD.
AB  - The incidence of cardiovascular events and mortality strongly correlates with
      serum phosphate in individuals with CKD. The Npt2b transporter contributes to
      maintaining phosphate homeostasis in the setting of normal renal function, but
      its role in CKD-associated hyperphosphatemia is not well understood. Here, we
      used adenine to induce uremia in both Npt2b-deficient and wild-type mice.
      Compared with wild-type uremic mice, Npt2b-deficient uremic mice had
      significantly lower levels of serum phosphate and attenuation of FGF23. Treating
      Npt2b-deficient mice with the phosphate binder sevelamer carbonate further
      reduced serum phosphate levels. Uremic mice exhibited high turnover renal
      osteodystrophy; treatment with sevelamer significantly decreased the number of
      osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but
      sevelamer did not affect bone formation and rate of mineral apposition in wild
      type mice. Taken together, these data suggest that targeting Npt2b in addition to
      using dietary phosphorus binders may be a therapeutic approach to modulate serum
      phosphate in CKD.

PMID- 22859852
TI  - Fcgamma receptor deficiency attenuates diabetic nephropathy.
AB  - Among patients with diabetes, increased production of immunoglobulins against
      proteins modified by diabetes is associated with proteinuria and cardiovascular
      risk, suggesting that immune mechanisms may contribute to the development of
      diabetes complications, such as nephropathy. We investigated the contribution of
      IgG Fcgamma receptors to diabetic renal injury in hyperglycemic,
      hypercholesterolemic mice. We used streptozotocin to induce diabetes in
      apolipoprotein E-deficient mice and in mice deficient in both apolipoprotein E
      and gamma-chain, the common subunit of activating Fcgamma receptors. After 15
      weeks, the mice lacking Fcgamma receptors had significantly less albuminuria and
      renal hypertrophy, despite similar degrees of hyperglycemia and
      hypercholesterolemia, immunoglobulin production, and glomerular immune deposits.
      Moreover, diabetic Fcgamma receptor-deficient mice had less mesangial matrix
      expansion, inflammatory cell infiltration, and collagen and alpha-smooth muscle
      actin content in their kidneys. Accordingly, expression of genes involved in
      leukocyte infiltration, fibrosis, and oxidative stress was significantly reduced
      in diabetic kidneys and in mesangial cells cultured from Fcgamma receptor
      deficient mice. In summary, preventing the activation of Fcgamma receptors
      alleviates renal hypertrophy, inflammation, and fibrosis in hypercholesterolemic
      mice with diabetes, suggesting that modulating Fcgamma receptor signaling may be
      renoprotective in diabetic nephropathy.

PMID- 22859853
TI  - Aquaporin 2 promotes cell migration and epithelial morphogenesis.
AB  - The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts,
      contributes critically to water homeostasis in mammals. Animals lacking or having
      significantly reduced levels of AQP2, however, have not only urinary
      concentrating abnormalities but also renal tubular defects that lead to neonatal
      mortality from renal failure. Here, we show that AQP2 is not only a water channel
      but also an integrin-binding membrane protein that promotes cell migration and
      epithelial morphogenesis. AQP2 expression modulates the trafficking and
      internalization of integrin beta1, facilitating its turnover at focal adhesions.
      In vitro, disturbing the interaction between AQP2 and integrin beta1 by mutating
      the RGD motif led to reduced endocytosis, retention of integrin beta1 at the cell
      surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2
      null mice exhibited significant retention of integrin beta1 at the basolateral
      membrane and had tubular abnormalities. In summary, these data suggest that the
      water channel AQP2 interacts with integrins to promote renal epithelial cell
      migration, contributing to the structural and functional integrity of the
      mammalian kidney.

PMID- 22859854
TI  - Activation of parenchymal CD47 promotes renal ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury (IRI) contributes to decreased allograft function and
      allograft rejection in transplanted kidneys. Thrombospondin-1 is a stress protein
      typically secreted in response to hypoxia and the ligand activator for the
      ubiquitously expressed receptor CD47. The function of activated CD47 in IRI
      remains completely unknown. Here, we found that both CD47 and its ligand
      thrombospondin-1 were upregulated after renal IRI in mice. CD47-knockout mice
      were protected against renal dysfunction and tubular damage, suggesting that the
      development of IRI requires intact CD47 signaling. Chimeric CD47-knockout mice
      engrafted with wild-type hematopoietic cells had significantly lower serum
      creatinine and less tubular damage than wild-type controls after IRI, suggesting
      that CD47 signaling in parenchymal cells predominantly mediates renal damage.
      Treatment with a CD47-blocking antibody protected mice from renal dysfunction and
      tubular damage compared with an isotype control. Taken together, these data imply
      that CD47 on parenchymal cells promotes injury after renal ischemia and
      reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent
      or suppress ischemia-reperfusion-mediated damage.

PMID- 22859855
TI  - Treatment of idiopathic membranous nephropathy.
AB  - Exciting progress recently has been made in our understanding of idiopathic
      membranous nephropathy, as well as treatment of this disease. Here, we review
      important advances regarding the pathogenesis of membranous nephropathy. We will
      also review the current approach to treatment and its limitations and will
      highlight new therapies that are currently being explored for this disease
      including Rituximab, mycophenolate mofetil, and adrenocorticotropic hormone, with
      an emphasis on results of the most recent clinical trials.

PMID- 22859856
TI  - Folate-conjugated rapamycin slows progression of polycystic kidney disease.
AB  - Activation of the mammalian target of rapamycin (mTOR) signaling pathway is
      aberrant in autosomal-dominant polycystic kidney disease (ADPKD). The mTOR
      inhibitors, such as rapamycin, ameliorate PKD in rodent models, but clinical
      trials have not shown benefit, possibly as a result of low tissue concentrations
      of rapamycin at clinically tolerable doses. To overcome this limitation, we
      synthesized a folate-conjugated form of rapamycin (FC-rapa) that is taken up by
      folate receptor-mediated endocytosis and cleaved intracellularly to reconstitute
      the active drug. We found that renal cyst-lining cells highly express the folate
      receptor in ADPKD and mouse models. In vitro, FC-rapa inhibited mTOR activity in
      a dose- and folate receptor-dependent manner. Treatment of a PKD mouse model with
      FC-rapa inhibited mTOR in the target tissue, strongly attenuated proliferation
      and growth of renal cysts and preserved renal function. Furthermore, FC-rapa
      inhibited mTOR activity in the kidney but not in other organs. In summary, these
      results suggest that targeting the kidney using FC-rapa may overcome the
      significant side effects and lack of renal efficacy observed in clinical trials
      with mTOR inhibitors in ADPKD.

PMID- 22859859
TI  - Nanoparticles modified by encapsulation of ligands with a long alkyl chain to
      affect multispecific and multimodal imaging.
AB  - The attachment of specific ligands to the surfaces of nanoparticles is important
      for medical and biologic imaging. However, covalent modification of nanoparticles
      has inherent problems in reproducibility because of many factors such as
      temperature, pH, concentration, and reaction time. Thus, we developed a method
      for modifying nanoparticles by encapsulation with specific ligand-conjugated
      amphiphiles. METHODS: We synthesized special amphiphiles with a hydrophilic head
      and a long single-alkyl chain, such as arginine-glycine-aspartic acid-C(18),
      mannose-C(18), lactose-C(18), and 2-(p-isothiocyanatobenzyl)-1,4,7
      triazacyclononane-1,4,7-triacetic acid-C(18). And then we produced stable quantum
      dots (QDs) encapsulated with polysorbate 60 (a branched polyethylene glycol head
      with a C(18) tail) and the synthesized special amphiphiles. The prepared
      encapsulated QDs were subject to in vitro and in vivo animal biodistribution
      studies and small-animal PET studies to confirm their specific binding. RESULTS:
      The encapsulated QDs could specifically bind to target cells in vitro and in vivo
      and could be labeled with (68)Ga (a positron emitter) easily and with high
      efficiency. CONCLUSION: The nanoparticles encapsulated with special amphiphiles
      could provide a straightforward and novel imaging solution with multimodality and
      multispecificity.

PMID- 22859860
TI  - Inhibition of smooth muscle cell proliferation by adiponectin requires
      proteolytic conversion to its globular form.
AB  - Accelerated atherosclerosis is the primary cardiovascular manifestation of
      diabetes and correlates inversely with levels of circulating adiponectin, an anti
      atherosclerotic adipokine that declines in diabetes. We therefore initiated a
      study to examine the mechanisms by which adiponectin, a hormone released from
      adipose tissue, influences the proliferation of vascular smooth muscle cells
      (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs
      increased both protein and DNA synthesis and concurrently activated ERK1/2 and
      Akt. By contrast, globular adiponectin, a truncated form of this protein,
      exhibited anti-mitogenic properties as indicated by the inhibition of protein and
      DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF).
      Whereas globular adiponectin did not stimulate growth-related signal transduction
      pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic
      elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of
      adiponectin with trypsin, which produces globular adiponectin, reversed the
      growth-stimulating actions of the undigested protein. As the existence of
      globular adiponectin remains controversial, western blotting was used to
      establish its presence in rat serum. We found that globular adiponectin was
      detectable in rat serum, but this result was not obtained with all antibodies.
      The contrasting properties of adiponectin and its globular form with respect to
      SMC proliferation suggest that protection against atherosclerosis may therefore
      be mediated, in part, by the level of globular adiponectin.

PMID- 22859861
TI  - Angiopoietin-2 enhances survival in experimental sepsis induced by multidrug
      resistant Pseudomonas aeruginosa.
AB  - Levels of circulating angiopoietin-2 (Ang-2) increase in sepsis, raising the
      possibility that Ang-2 acts as a modulator in the sepsis cascade. To investigate
      this, experimental sepsis was induced in male C57BL6 mice by a multidrug
      resistant isolate of Pseudomonas aeruginosa; survival was determined along with
      neutrophil tissue infiltration and release of proinflammatory cytokines. Survival
      was significantly increased either by pretreatment with recombinant Ang-2 2 h
      before or treatment with recombinant Ang-2 30 min after bacterial challenge.
      Likewise, Ang-2 pretreatment protected against sepsis-related death elicited by
      Escherichia coli; however, Ang-2 failed to provide protection in
      lipopolysaccharide (LPS)-challenged mice. The survival advantage of Ang-2 in
      response to P. aeruginosa challenge was lost in tumor necrosis factor (TNF)
      deficient mice or neutropenic mice. Infiltration of the liver by neutrophils was
      elevated in the Ang-2 group compared with saline-treated animals. Serum TNF-alpha
      levels were reduced by Ang-2, whereas those of interleukin (IL)-6 and IL-10
      remained unchanged. This was accompanied by lower release of TNF-alpha by
      stimulated splenocytes. When applied to U937 cells in vitro, heat-killed P.
      aeruginosa induced the secretion of IL-6 and TNF-alpha; low levels of exogenous
      TNF-alpha synergized with P. aeruginosa. This synergistic effect was abolished
      after the addition of Ang-2. These results put in evidence a striking protective
      role of Ang-2 in experimental sepsis evoked by a multidrug-resistant isolate of
      P. aeruginosa attributed to modulation of TNF-alpha production and changes in
      neutrophil migration. The protective role of Ang-2 is shown when whole
      microorganisms are used and not LPS, suggesting complex interactions with the
      host immune response.

PMID- 22859857
TI  - Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.
AB  - Inflammation and oxidative stress are hallmarks and mediators of the progression
      of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2
      related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response,
      increases estimated GFR and decreases BUN, serum phosphorus, and uric acid
      concentrations in patients with moderate to severe CKD. However, it also
      increases albuminuria, which is associated with inflammation and disease
      progression. Therefore, we investigated whether this bardoxolone methyl-induced
      albuminuria may result from the downregulation of megalin, a protein involved in
      the tubular reabsorption of albumin and lipid-bound proteins. Administration of
      bardoxolone methyl to cynomolgus monkeys significantly decreased the protein
      expression of renal tubular megalin, which inversely correlated with the urine
      albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone
      methyl to monkeys for 1 year did not lead to any adverse effects on renal
      histopathologic findings but did reduce serum creatinine and BUN, as observed in
      patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin
      corresponded with pharmacologic induction of renal Nrf2 targets, including
      NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This
      result indicates that Nrf2 may have a role in megalin regulation. In conclusion,
      these data suggest that the increase in albuminuria that accompanies bardoxolone
      methyl administration may result, at least in part, from reduced expression of
      megalin, which seems to occur without adverse effects and with strong induction
      of Nrf2 targets.

PMID- 22859863
TI  - CLOSED-FORM ASYMPTOTIC SAMPLING DISTRIBUTIONS UNDER THE COALESCENT WITH
      RECOMBINATION FOR AN ARBITRARY NUMBER OF LOCI.
AB  - Obtaining a closed-form sampling distribution for the coalescent with
      recombination is a challenging problem. In the case of two loci, a new framework
      based on asymptotic series has recently been developed to derive closed-form
      results when the recombination rate is moderate to large. In this paper, an
      arbitrary number of loci is considered and combinatorial approaches are employed
      to find closed-form expressions for the first couple of terms in an asymptotic
      expansion of the multi-locus sampling distribution. These expressions are
      universal in the sense that their functional form in terms of the marginal one
      locus distributions applies to all finite- and infinite-alleles models of
      mutation.

PMID- 22859864
TI  - Better Off Jobless? Scarring Effects of Contingent Employment in Japan.
AB  - Previous research fails to address whether contingent employment benefits
      individuals' careers more than the alternative they often face: being without a
      job. Using work history data from Japan, this study shows that accepting a
      contingent job delays individuals' transition to standard employment more than
      remaining jobless. Moreover, having a contingent job, rather than having no job,
      leads Japanese men to have lower occupational status after they transition back
      to standard employment. I argue that in a highly segmented labor market like
      Japan's, the strict separation of labor pools for standard and contingent jobs
      makes being labeled as a contingent worker particularly detrimental. Meanwhile,
      the legacy of Japan's welfare corporatism alleviates the stigma of unemployment,
      making individuals better off jobless than having a contingent job. This research
      thus demonstrates the importance of labor-market contexts in shaping the scarring
      effects of contingent work arrangements.

PMID- 22859862
TI  - Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.
AB  - Based on the observation that antipsychotic medications display antagonist
      properties at dopamine D2-like receptors, aberrant dopamine signaling has been
      proposed to underlie psychosis in patients with schizophrenia. Thus, it is not
      surprising that considerable research has been devoted to understanding the
      mechanisms involved in the antipsychotic action of these compounds. It is
      important to note that the majority of these studies have been performed in
      "normal" experimental animals. Given that these animals do not possess the
      aberrant neuronal information processing typically associated with schizophrenia,
      the aim of the current study was to examine the dopamine D2 receptor system in a
      rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol
      acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine
      neuron activity and an aberrant locomotor response to D2-like receptor
      activation, suggesting changes in postsynaptic D2-like receptor function. To
      better understand the mechanisms underlying the enhanced response to D2-like
      ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine
      transporter mRNA in the nucleus accumbens and ventral tegmental area by
      quantitative reverse transcription-polymerase chain reaction. MAM-treated rats
      displayed a significant increase in dopamine D3 receptor mRNA expression in the
      nucleus accumbens with no significant changes in the expression of the D2
      receptor. Taken together, these data demonstrate robust alterations in dopamine
      D2-like receptor function in a rodent model of schizophrenia and provide evidence
      that preclinical studies examining the mechanisms of antipsychotic drug action
      should be performed in animal models that mirror aspects of the abnormal neuronal
      transmission thought to underlie symptoms of schizophrenia.

PMID- 22859865
TI  - Enantioselective total synthesis of callipeltoside A: two approaches to the
      macrolactone fragment.
AB  - The enantioselective total synthesis of callipeltoside A is described. Two
      syntheses of the macrolactone subunit are included: the first relies upon an
      Ireland-Claisen rearrangement to generate the trisubstituted olefin geometry and
      the second utilizes an enantioselective vinylogous aldol reaction for this
      purpose. Enantioselective syntheses of the sugar and chlorocyclopropane side
      chain fragments are also disclosed. The relative and absolute stereochemistry of
      this natural product was determined by fragment coupling with the two enantiomers
      of the side chain fragment.

PMID- 22859867
TI  - Hemoptysis after subclavian vein puncture for pacemaker implantation: importance
      of wire-guided venous puncture.
AB  - We report a case of hemoptysis occurring after subclavian vein puncture for
      pacemaker implantation. Hemoptysis related to injury of lung parenchyma is a rare
      complication of subclavian vein access and is usually self limited, but can
      affect prognosis in critically ill patients. Venogram-guided or even better wire
      guided venous puncture allow safe access to the subclavian vein in difficult
      cases. A review of the pertinent literature is also presented.

PMID- 22859868
TI  - Sexual dimorphism in shells of Cochlostoma septemspirale (Caenogastropoda,
      Cyclophoroidea, Diplommatinidae, Cochlostomatinae).
AB  - Sexual dimorphisms in shell-bearing snails expressed by characteristic traits of
      their respective shells would offer the possibility for a lot of studies about
      gender distribution in populations, species, etc. In this study, the seven main
      shell characters of the snail Cochlostoma septemspirale were measured in both
      sexes: (1) height and (2) width of the shell, (3) height and (4) width of the
      aperture, (5) width of the last whorl, (6) rib density on the last whorl, and (7)
      intensity of the reddish or brown pigments forming three bands over the shell.
      The variation of size and shape was explored with statistical methods adapted to
      principal components analysis (PCA) and linear discriminant analysis (LDA). In
      particular, we applied some multivariate morphometric tools for the analysis of
      ratios that have been developed only recently, that is, the PCA ratio spectrum,
      allometry ratio spectrum, and LDA ratio extractor. The overall separation of the
      two sexes was tested with LDA cross validation.The results show that there is a
      sexual dimorphism in the size and shape of shells. Females are more slender than
      males and are characterised by larger size, a slightly reduced aperture height
      but larger shell height and whorl width. Therefore they have a considerable
      larger shell volume (about one fifth) in the part above the aperture.
      Furthermore, the last whorl of females is slightly less strongly pigmented and
      mean rib density slightly higher. All characters overlap quite considerably
      between sexes. However, by using cross validation based on the 5 continuous shell
      characters more than 90% of the shells can be correctly assigned to each sex.

PMID- 22859869
TI  - A new species and new records of Laelaspis Berlese (Acari, Laelapidae) from Iran.
AB  - This paper reports on three species of mites of the genus Laelaspis in Iran -
      Laelaspis calidus Berlese from Pheidole pallidula, Laelaspis humeratus (Berlese)
      from Tetramorium caespitum and Laelaspis dariusi Joharchi & Jalaeian, sp. n.
      fromsoil. The new species is described and illustrations provided.

PMID- 22859870
TI  - Surprising longhorned beetle (Coleoptera, Cerambycidae) richness along an Italian
      alpine valley.
AB  - In this paper we report about 88 longhorned beetles (Cerambycidae) species found
      in 6929 hectares and distributed along an altitudinal gradient of 1500 m of an
      Italian alpine valley (Val Genova, central-eastern Italian Alps). The species
      richness, result merging data from sixty years (1947-2007) of entomological
      surveys, corresponds to the 32% of the Italian cerambycid fauna confirming the
      high richness/surface ratio, probably unique in the Alps. The effect of thirteen
      environmental variables was tested on the species richness, but only the
      elevation resulted able to affect it. The species richness decrease with altitude
      not gradually, but experience a strong step above 1700 m a.s.l.. The highest
      species richness (average values of 42 species) was recorded at the lowest and
      mid elevations (between 800 and 1600 m a.s.l.). The species turnover along the
      altitudinal gradient is low suggesting moderate habitat turnover along the
      valley.One of the eighty-eight observed species, Tragosoma depsarium,is
      classified near threatened by the IUCN. Our data suggest that the wilderness of
      the valley close to the suitable management of grasslands and forests, help to
      support high level of cerambycids diversity. This biodiversity is good indicators
      of health of the wood saproxylic assemblages, as well an important food source
      for many vertebrate predators.

PMID- 22859871
TI  - Two new species of Olecryptotendipes Zorina, 2007 from China (Diptera,
      Chironomidae).
AB  - Two new species, Olecryptotendipes exilissp. n. and Olecryptotendipes melasmussp.
      n. are described and illustrated as males and Chinese males of Olecryptotendipes
      lenzi are re-examined. A key to all known males of Olecryptotendipes is provided.

PMID- 22859872
TI  - Two new species of Bryophaenocladius Thienemann, 1934 (Diptera, Chironomidae)
      from China.
AB  - Two new species of Bryophaenocladius Thienemann, 1934, Bryophaenocladius
      mucronatussp. n. and Bryophaenocladius parictericussp. n. are described and
      illustrated as males. A key to male imagines of the genus from China is
      presented.

PMID- 22859873
TI  - Mariapanteles (Hymenoptera, Braconidae), a new genus of Neotropical microgastrine
      parasitoid wasp discovered through biodiversity inventory.
AB  - A new genus of microgastrine parasitoid wasps, Mariapanteles Whitfield &
      Fernandez-Triana, gen. n., is described from rain forests of the Neotropics. The
      new genus is related to the common and speciose genus Pseudapanteles, but can be
      distinguished from the latter by having a complete transverse carina on the
      propodeum which forks around the spiracles. A molecular analysis based on data
      from COI from specimens of the proposed new genus plus possibly related genera
      confirms its generic distinctness. A key to two known species, Mariapanteles
      felipei Whitfield, sp. n. (Costa Rica) and Mariapanteles dapkeyae Fernandez
      Triana, sp. n. (Brazil) is provided. Evidence from collections suggests that
      there are other undescribed Neotropical congenerics. Specimens of Mariapanteles
      were likely confused in the past with the genus Beyarslania (referred to as
      Xenogaster until recently) but present information suggests that Beyarslania is
      restricted to the Afrotropical region while the Neotropical species clearly
      belong to a different genus, which we propose as new.

PMID- 22859874
TI  - Bringing collections out of the dark.

PMID- 22859875
TI  - Mass digitization of scientific collections: New opportunities to transform the
      use of biological specimens and underwrite biodiversity science.
AB  - New information technologies have enabled the scientific collections community
      and its stakeholders to adapt, adopt, and leverage novel approaches for a nearly
      300 years old scientific discipline. Now, few can credibly question the
      transformational impact of technology on efforts to digitize scientific
      collections, as IT now reaches into almost every nook and cranny of society. Five
      to ten years ago this was not the case. Digitization is an activity that museums
      and academic institutions increasingly recognize, though many still do not
      embrace, as a means to boost the impact of collections to research and society
      through improved access. The acquisition and use of scientific collections is a
      global endeavor, and digitization enhances their value by improved access to core
      biodiversity information, increases use, relevance and potential downstream
      value, for example, in the management of natural resources, policy development,
      food security, and planetary and human health. This paper examines new
      opportunities to design and implement infrastructure that will support not just
      mass digitization efforts, but also a broad range of research on biological
      diversity and physical sciences in order to make scientific collections
      increasingly relevant to societal needs and interest.

PMID- 22859876
TI  - Five task clusters that enable efficient and effective digitization of biological
      collections.
AB  - This paper describes and illustrates five major clusters of related tasks (herein
      referred to as task clusters) that are common to efficient and effective
      practices in the digitization of biological specimen data and media. Examples of
      these clusters come from the observation of diverse digitization processes. The
      staff of iDigBio (The U.S. National Science Foundation's National Resource for
      Advancing Digitization of Biological Collections) visited active biological and
      paleontological collections digitization programs for the purpose of documenting
      and assessing current digitization practices and tools. These observations
      identified five task clusters that comprise the digitization process leading up
      to data publication: (1) pre-digitization curation and staging, (2) specimen
      image capture, (3) specimen image processing, (4) electronic data capture, and
      (5) georeferencing locality descriptions. While not all institutions are
      completing each of these task clusters for each specimen, these clusters describe
      a composite picture of digitization of biological and paleontological specimens
      across the programs that were observed. We describe these clusters, three
      workflow patterns that dominate the implemention of these clusters, and offer a
      set of workflow recommendations for digitization programs.

PMID- 22859877
TI  - OpenUp! Creating a cross-domain pipeline for natural history data.
AB  - Multimedia data held by Natural History Museums and Universities are presently
      not readily accessible, even within the natural history community itself. The EU
      project OpenUp! is an effort to mobilise scientific biological multimedia
      resources and open them to a wider audience using the EUROPEANA data standards
      and portal. The connection between natural history and EUROPEANA is accomplished
      using well established BioCASe and GBIF technologies. This is complemented with a
      system for data quality control, data transformation and semantic enrichment.
      With this approach, OpenUp! will provide at least 1,1 Million multimedia objects
      to EUROPEANA by 2014. Its lean infrastructure is sustainable within the natural
      history community and will remain functional and effective in the post-project
      phase.

PMID- 22859878
TI  - The US Virtual Herbarium: working with individual herbaria to build a national
      resource.
AB  - The goal of the US Virtual Herbarium (USVH) project is to digitize (database,
      image, georeference) all specimens in all US herbaria, enabling them to be made
      available through a single portal. Herbaria house specimens of plants, fungi, and
      algae, so USVH will offer a rich portrait of biodiversity in the US and in the
      other countries represented in US herbaria. Equally importantly, working towards
      this goal will engage people with herbaria and the organisms they house,
      expanding their appreciation of both the power of biodiversity informatics and
      the demands that it places on data providers while developing improved
      communication among those working in and with herbaria. The project is not funded
      but has strong support among those working in herbaria. It works through regional
      herbarium networks, some of which existed prior to the USVH project, while others
      are still in gestation. It differs from most digitization projects in its
      emphasis on helping those involved with herbaria become part of a national
      enterprise, an aspect that is seen as critical to creating the resources needed
      to develop and sustain the project. In this paper, we present some of the lessons
      we have learned and the difficulties we have encountered during the first few
      years of the project.

PMID- 22859879
TI  - The development of a digitising service centre for natural history collections.
AB  - Digitarium is a joint initiative of the Finnish Museum of Natural History and the
      University of Eastern Finland. It was established in 2010 as a dedicated shop for
      the large-scale digitisation of natural history collections. Digitarium offers
      service packages based on the digitisation process, including tagging, imaging,
      data entry, georeferencing, filtering, and validation. During the process, all
      specimens are imaged, and distance workers take care of the data entry from the
      images. The customer receives the data in Darwin Core Archive format, as well as
      images of the specimens and their labels. Digitarium also offers the option of
      publishing images through Morphbank, sharing data through GBIF, and archiving
      data for long-term storage. Service packages can also be designed on demand to
      respond to the specific needs of the customer. The paper also discusses
      logistics, costs, and intellectual property rights (IPR) issues related to the
      work that Digitarium undertakes.

PMID- 22859880
TI  - 'From Pilot to production': Large Scale Digitisation project at Naturalis
      Biodiversity Center.
AB  - By the end of 2009 the Dutch Government awarded the establishment of NCB
      Naturalis with ?30M funding. The amount is invested in three programs: Scientific
      Infrastructure for DNA Barcoding, Integration and Relocation of collections and
      Collection Digitisation. In this article we describe the highlights of the
      Digitisation Programme.

PMID- 22859881
TI  - Developing integrated workflows for the digitisation of herbarium specimens using
      a modular and scalable approach.
AB  - Digitisation programmes in many institutes frequently involve disparate and
      irregular funding, diverse selection criteria and scope, with different members
      of staff managing and operating the processes. These factors have influenced the
      decision at the Royal Botanic Garden Edinburgh to develop an integrated workflow
      for the digitisation of herbarium specimens which is modular and scalable to
      enable a single overall workflow to be used for all digitisation projects. This
      integrated workflow is comprised of three principal elements: a specimen
      workflow, a data workflow and an image workflow.The specimen workflow is strongly
      linked to curatorial processes which will impact on the prioritisation, selection
      and preparation of the specimens. The importance of including a conservation
      element within the digitisation workflow is highlighted. The data workflow
      includes the concept of three main categories of collection data: label data,
      curatorial data and supplementary data. It is shown that each category of data
      has its own properties which influence the timing of data capture within the
      workflow. Development of software has been carried out for the rapid capture of
      curatorial data, and optical character recognition (OCR) software is being used
      to increase the efficiency of capturing label data and supplementary data. The
      large number and size of the images has necessitated the inclusion of automated
      systems within the image workflow.

PMID- 22859882
TI  - Increasing the efficiency of digitization workflows for herbarium specimens.
AB  - The New York Botanical Garden Herbarium has been databasing and imaging its
      estimated 7.3 million plant specimens for the past 17 years. Due to the size of
      the collection, we have been selectively digitizing fundable subsets of
      specimens, making successive passes through the herbarium with each new grant.
      With this strategy, the average rate for databasing complete records has been 10
      specimens per hour. With 1.3 million specimens databased, this effort has taken
      about 130,000 hours of staff time. At this rate, to complete the herbarium and
      digitize the remaining 6 million specimens, another 600,000 hours would be
      needed. Given the current biodiversity and economic crises, there is neither the
      time nor money to complete the collection at this rate.Through a combination of
      grants over the last few years, The New York Botanical Garden has been testing
      new protocols and tactics for increasing the rate of digitization through
      combinations of data collaboration, field book digitization, partial data entry
      and imaging, and optical character recognition (OCR) of specimen images. With the
      launch of the National Science Foundation's new Advancing Digitization of
      Biological Collections program, we hope to move forward with larger, more
      efficient digitization projects, capturing data from larger portions of the
      herbarium at a fraction of the cost and time.

PMID- 22859883
TI  - Results and insights from the NCSU Insect Museum GigaPan project.
AB  - Pinned insect specimens stored in museum collections are a fragile and valuable
      resource for entomological research. As such, they are usually kept away from
      viewing by the public and hard to access by experts. Here we present a method for
      mass imaging insect specimens, using GigaPan technology to achieve highly
      explorable, many-megapixel panoramas of insect museum drawers. We discuss the
      advantages and limitations of the system, and describe future avenues of
      collections research using this technology.

PMID- 22859884
TI  - No specimen left behind: industrial scale digitization of natural history
      collections.
AB  - Traditional approaches for digitizing natural history collections, which include
      both imaging and metadata capture, are both labour- and time-intensive. Mass
      digitization can only be completed if the resource-intensive steps, such as
      specimen selection and databasing of associated information, are minimized.
      Digitization of larger collections should employ an "industrial" approach, using
      the principles of automation and crowd sourcing, with minimal initial metadata
      collection including a mandatory persistent identifier. A new workflow for the
      mass-digitization of natural history museum collections based on these
      principles, and using SatScan(r) tray scanning system, is described.

PMID- 22859885
TI  - Whole-drawer imaging for digital management and curation of a large entomological
      collection.
AB  - Whole-drawer imaging is shown to be an effective tool for rapid digitisation of
      large insect collections. On-line, Whole-drawer images facilitate more effective
      collection management, virtual curation, and public engagement. The Whole-drawer
      imaging experience at the Australian National Insect Collection is discussed,
      with an explanation of workflow and examples of benefits.

PMID- 22859886
TI  - InvertNet: a new paradigm for digital access to invertebrate collections.
AB  - InvertNet, one of the three Thematic Collection Networks (TCNs) funded in the
      first round of the U.S. National Science Foundation's Advancing Digitization of
      Biological Collections (ADBC) program, is tasked with providing digital access to
      ~60 million specimens housed in 22 arthropod (primarily insect) collections at
      institutions distributed throughout the upper midwestern USA. The traditional
      workflow for insect collection digitization involves manually keying information
      from specimen labels into a database and attaching a unique identifier label to
      each specimen. This remains the dominant paradigm, despite some recent attempts
      to automate various steps in the process using more advanced technologies.
      InvertNet aims to develop improved semi-automated, high-throughput workflows for
      digitizing and providing access to invertebrate collections that balance the need
      for speed and cost-effectiveness with long-term preservation of specimens and
      accuracy of data capture. The proposed workflows build on recent methods for
      digitizing and providing access to high-quality images of multiple specimens
      (e.g., entire drawers of pinned insects) simultaneously. Limitations of previous
      approaches are discussed and possible solutions are proposed that incorporate
      advanced imaging and 3-D reconstruction technologies. InvertNet couples efficient
      digitization workflows with a highly robust network infrastructure capable of
      managing massive amounts of image data and related metadata and delivering high
      quality images, including interactive 3-D reconstructions in real time via the
      Internet.

PMID- 22859887
TI  - DScan - a high-performance digital scanning system for entomological collections.
AB  - Here we describe a high-performance imaging system for creating high-resolution
      images of whole insect drawers. All components of the system are industrial
      standard and can be adapted to meet the specific needs of entomological
      collections. A controlling unit allows the setting of imaging area (drawer size),
      step distance between individual images, number of images, image resolution, and
      shooting sequence order through a set of parameters. The system is highly
      configurable and can be used with a wide range of different optical hardware and
      image processing software.

PMID- 22859888
TI  - Nomenclatural benchmarking: the roles of digital typification and telemicroscopy.
AB  - Nomenclatural benchmarking is the periodic realignment of species names with
      species theories and is necessary for the accurate and uniform use of Linnaean
      binominals in the face of changing species limits. Gaining access to types, often
      for little more than a cursory examination by an expert, is a major bottleneck in
      the advance and availability of biodiversity informatics. For the nearly two
      million described species it has been estimated that five to six million name
      bearing type specimens exist, including those for synonymized binominals.
      Recognizing that examination of types in person will remain necessary in special
      cases, we propose a four-part strategy for opening access to types that relies
      heavily on digitization and that would eliminate much of the bottleneck: (1)
      modify codes of nomenclature to create registries of nomenclatural acts, such as
      the proposed ZooBank, that include a requirement for digital representations (e
      types) for all newly described species to avoid adding to backlog; (2) an "r"
      strategy that would engineer and deploy a network of automated instruments
      capable of rapidly creating 3-D images of type specimens not requiring
      participation of taxon experts; (3) a "K" strategy using remotely operable
      microscopes to engage taxon experts in targeting and annotating informative
      characters of types to supplement and extend information content of rapidly
      acquired e-types, a process that can be done on an as-needed basis as in the
      normal course of revisionary taxonomy; and (4) creation of a global e-type
      archive associated with the commissions on nomenclature and species registries
      providing one-stop-shopping for e-types. We describe a first generation
      implementation of the "K" strategy that adapts current technology to create a
      network of Remotely Operable Benchmarkers Of Types (ROBOT) specifically
      engineered to handle the largest backlog of types, pinned insect specimens. The
      three initial instruments will be in the Smithsonian Institution(Washington, DC),
      Natural History Museum (London), and Museum National d'Histoire Naturelle
      (Paris), networking the three largest insect collections in the world with
      entomologists worldwide. These three instruments make possible remote
      examination, manipulation, and photography of types for more than 600,000
      species. This is a cybertaxonomy demonstration project that we anticipate will
      lead to similar instruments for a wide range of museum specimens and objects as
      well as revolutionary changes in collaborative taxonomy and formal and public
      taxonomic education.

PMID- 22859889
TI  - Image based Digitisation of Entomology Collections: Leveraging volunteers to
      increase digitization capacity.
AB  - In 2010, the Australian Museum commenced a project to explore and develop ways
      for engaging volunteers to increase the rate of digitising natural history
      collections. The focus was on methods for image-based digitising of dry pinned
      entomology collections. With support from the Atlas of Living Australia, the
      Australian Museum developed a team of volunteers, training materials and
      processes and procedures.Project officers were employed to coordinate the
      volunteer workforce. Digitising workstations were established with the aim of
      minimising cost whilst maximising productivity and ease of use. Database
      management and curation of material before digitisation, were two areas that
      required considerably more effort than anticipated.Productivity of the
      workstations varied depending on the species group being digitised. Fragile
      groups took longer, and because digitising rates vary among the volunteers, the
      average hourly rate for digitising pinned entomological specimens (cicadas,
      leafhoppers, moths, beetles, flies) varied between 15 to 20 per workstation per
      hour, which compares with a direct data entry rate of 18 per hour from previous
      trials.Four specimen workstations operated four days a week, five hours a day, by
      a team of over 40 volunteers. Over 5 months, 16,000 specimens and their labels
      were imaged and entered as short records into the museum's collection management
      database.

PMID- 22859890
TI  - The notes from nature tool for unlocking biodiversity records from museum records
      through citizen science.
AB  - Legacy data from natural history collections contain invaluable and irreplaceable
      information about biodiversity in the recent past, providing a baseline for
      detecting change and forecasting the future of biodiversity on a human-dominated
      planet. However, these data are often not available in formats that facilitate
      use and synthesis. New approaches are needed to enhance the rates of digitization
      and data quality improvement. Notes from Nature provides one such novel approach
      by asking citizen scientists to help with transcription tasks. The initial web
      based prototype of Notes from Nature is soon widely available and was developed
      collaboratively by biodiversity scientists, natural history collections staff,
      and experts in citizen science project development, programming and
      visualization. This project brings together digital images representing different
      types of biodiversity records including ledgers , herbarium sheets and pinned
      insects from multiple projects and natural history collections. Experts in
      developing web-based citizen science applications then designed and built a
      platform for transcribing textual data and metadata from these images. The end
      product is a fully open source web transcription tool built using the latest web
      technologies. The platform keeps volunteers engaged by initially explaining the
      scientific importance of the work via a short orientation, and then providing
      transcription "missions" of well defined scope, along with dynamic feedback,
      interactivity and rewards. Transcribed records, along with record-level and
      process metadata, are provided back to the institutions.  While the tool is being
      developed with new users in mind, it can serve a broad range of needs from novice
      to trained museum specialist. Notes from Nature has the potential to speed the
      rate of biodiversity data being made available to a broad community of users.

PMID- 22859891
TI  - From documents to datasets: A MediaWiki-based method of annotating and extracting
      species observations in century-old field notebooks.
AB  - Part diary, part scientific record, biological field notebooks often contain
      details necessary to understanding the location and environmental conditions
      existent during collecting events. Despite their clear value for (and recent use
      in) global change studies, the text-mining outputs from field notebooks have been
      idiosyncratic to specific research projects, and impossible to discover or re
      use. Best practices and workflows for digitization, transcription, extraction,
      and integration with other sources are nascent or non-existent. In this paper, we
      demonstrate a workflow to generate structured outputs while also maintaining
      links to the original texts. The first step in this workflow was to place already
      digitized and transcribed field notebooks from the University of Colorado Museum
      of Natural History founder, Junius Henderson, on Wikisource, an open text
      transcription platform. Next, we created Wikisource templates to document places,
      dates, and taxa to facilitate annotation and wiki-linking. We then requested help
      from the public, through social media tools, to take advantage of volunteer
      efforts and energy. After three notebooks were fully annotated, content was
      converted into XML and annotations were extracted and cross-walked into Darwin
      Core compliant record sets. Finally, these recordsets were vetted, to provide
      valid taxon names, via a process we call "taxonomic referencing." The result is
      identification and mobilization of 1,068 observations from three of Henderson's
      thirteen notebooks and a publishable Darwin Core record set for use in other
      analyses. Although challenges remain, this work demonstrates a feasible approach
      to unlock observations from field notebooks that enhances their discovery and
      interoperability without losing the narrative context from which those
      observations are drawn."Compose your notes as if you were writing a letter to
      someone a century in the future."Perrine and Patton (2011).

PMID- 22859892
TI  - Integrating specimen databases and revisionary systematics.
AB  - Arguments are presented for the merit of integrating specimen databases into the
      practice of revisionary systematics. Work flows, data connections, data outputs,
      and data standardization are enumerated as critical aspects of such integration.
      Background information is provided on the use of "barcodes" as unique specimen
      identifiers and on methods for efficient data capture. Examples are provided on
      how to achieve efficient workflows and data standardization, as well as data
      outputs and data integration.

PMID- 22859893
TI  - Two new species of Megacanthaspis Takagi (Hemiptera, Sternorrhyncha, Coccoidea,
      Diaspididae) from China.
AB  - Two new species of armored scale, Megacanthaspis hangzhouensis Wei & Feng, sp. n.
      and Megacanthaspis hainanensis Wei & Feng, sp. n. are described and illustrated
      from specimens collected from China. A key to adult female of Megacanthaspis
      species is provided.

PMID- 22859894
TI  - A new species of Pseudaulacaspis MacGillivray, 1921 from China (Hemiptera,
      Coccoidea, Diaspididae) with a key to Chinese species.
AB  - A new species of armored scale, Pseudaulacaspis zhenyuanensis Wei & Feng, sp. n.
      is described and illustrated from specimens collected on Spermadictyon suaveolens
      in China. A key to armored scale species known from China is provided.

PMID- 22859895
TI  - Notes about morphological features of the Western Hemisphere subtribe
      Ardistomina, and revision of genus Semiardistomis Kult (Coleoptera, Carabidae,
      Scaritinae, Clivinini).
AB  - Comparisons of structural features (principally mouthparts, elytral-abdominal
      locking mechanism, and female genitalia) of the ardistomine genera (Aspidoglossa
      Putzeys, Ardistomis Putzeys, and Semiardistomis Kult) with those features of
      members of the subtribe Clivinina (Clivina Latreille, Oxydrepanus Putzeys,
      Schizogenius Putzeys,Ancus Putzeys, Nyctosyles Putzeys, and Obadius Burmeister)
      confirm the taxonomic validity of the subtribe Ardistomina. Based on
      morphological features, the ardistomine genera are postulated to be related as
      follows: [Aspidoglossa [Ardistomis + Semiardistomis]]. Knowledge of this subtribe
      is further extended by taxonomic treatment of the genus Semiardistomis Kult. Of
      the 30 valid names of Semiardistomis previously recognized, four were proposed as
      variety names, and are listed as junior synonyms: Ardistomis labialis picipes
      Bates, 1881, Ardistomis labialis nanus Bates, 1881, and Ardistomis labialis
      dilatatus Bates, 1881; and Ardistomis pallipes caerulea Putzeys, 1846. Eight
      names, treated as specific epithets, are junior synonyms, as follows: Ardistomis
      (Semiardistomis) balthasari Kult, 1950 = Semiardistomis glabratus (Putzeys,
      1866); Ardistomis (Semiardistomis) emdeni Kult, 1950 = Semiardistomis deletus
      (Putzeys, 1846); Ardistomis aenea Putzeys, 1866, Ardistomis (Semiardistomis)
      brittoni Kult, 1950, and Ardistomis (Semiardistomis) marani Kult, 1950 =
      Semiardistomis flavipes (Dejean, 1831); Ardistomis tuspanensis Putzeys, 1846 =
      Semiardistomis labialis (Chaudoir, 1837); Ardistomis (Semiardistomis) vlastae
      Kult, 1950 = Semiardistomis subglabra (van Emden, 1949); and Ardistomis striga
      Putzeys, 1866 = Semiardistomis pallipes (Dejean, 1831). Two new species described
      are Semiardistomis exspectatussp. n.(type locality PERU, Madre de Dios, Rio Manu,
      11 degrees 56'47"S, 071 degrees 17'00"W), and Semiardistomis majorsp. n. (type
      locality PERU, Loreto, Rio Samiria, 05 degrees 12'S, 75 degrees 20'W). The 20
      species of Semiardistomis are arranged intwo species-groups here proposed: the
      puncticollis group, including 12 species; and labialis group, including eight
      species. The species recognized are keyed, described or redescribed, and notes
      are provided about their Geographical distribution, habitat and activity.
      Distribution maps show known geographical ranges, from which are inferred
      patterns of speciation from a center of radiation in northern South America of
      both lineages.

PMID- 22859896
TI  - A new species of Peucoglyphus Bernhauer from New Guinea (Coleoptera,
      Staphylinidae, Staphylininae).
AB  - Peucoglyphus kensp. n., a new species from New Guinea is described. Adding the
      new species, this rare Wallacean genus from the tribe Staphylinini (subtribe
      Philonthina) currently includes five species. An updated identification key for
      the genus is provided.

PMID- 22859897
TI  - A new genus of oak gallwasps, Zapatella Pujade-Villar & Melika, gen. n., with a
      description of two new species from the Neotropics (Hymenoptera, Cynipidae,
      Cynipini).
AB  - A new genus of cynipid oak gallwasp, Zapatella Pujade-Villar & Melika, gen. n.
      (Hymenoptera: Cynipidae: Cynipini), with two new species, Zapatella grahami
      Pujade-Villar & Melika, sp. n. and Zapatella nievesaldreyi Melika & Pujade
      Villar, sp. n., is described from the Neotropics. Zapatella grahami,known only
      from the sexual generation,induces galls in acorns of Quercus costaricensis and
      is currently known only from Costa Rica. Zapatella nievesaldreyi, known only from
      the asexual generation, induces inconspicuous galls in twigs of Quercus
      humboldtii, and is known only from Colombia. Diagnostic characters for both new
      species are given in detail. Five Nearctic species are transferred from
      Callirhytis to Zapatella: Zapatella cryptica (Weld), comb. n., Zapatella herberti
      (Weld), comb. n., Zapatella oblata (Weld), comb. n., Zapatella quercusmedullae
      (Ashmead), comb. n.,Zapatella quercusphellos (Osten Sacken), comb. n. (=
      Zapatella quercussimilis (Bassett), syn. n.). A key based on adults for the
      species belonging to Zapatella is also given. Generic limits and morphological
      characteristics of Zapatella and closely related genera are discussed.

PMID- 22859898
TI  - Post-reperfusion syndrome during renal transplantation: a retrospective study.
AB  - Post-reperfusion syndrome (PRS) is a serious, widely reported complication
      following the reperfusion of an ischemic tissue or organ. We sought to determine
      the prevalence, risk factors and short-term outcomes of PRS related renal
      transplantation. We conducted a retrospective, case-control study of patients
      undergoing renal transplantation between July 2006 and March 2008. Identification
      of PRS was based on a drop in mean arterial pressure by at least 15% within 5
      minutes of donor kidney reperfusion. Of the 150 consecutive renal
      transplantations reviewed, 6 patients (4%) met criteria for post-reperfusion
      syndrome. Univariate analysis showed that an age over 60, diabetes mellitus,
      Asian race, and extended criteria donors increased the odds of developing PRS by
      4.8 times (95% CI [1.2, 20]; P=.0338), 4.5 times (95% CI [1.11, 18.8]; P=.0378),
      35.5 times (95% CI [3.94, 319.8]; P=0.0078) and 9.6 times (95% CI [1.19, 76.28]
      P=0.0115) respectively. Short term follow-up revealed increased graft failure
      rate within 6 months (6% vs. 16% P=0.0125) and almost twice the number of
      hospital days post-transplant in PRS cohorts (5.43 +/- 2.29 vs. 10.8 +/- 7.29
      P=<0.0001). Despite limited reporting, PRS appears to be a relatively common
      complication of renal transplantation and is associated with increase morbidity.

PMID- 22859899
TI  - Effects of antiretroviral therapy on autonomic function in early HIV infection: a
      preliminary report.
AB  - BACKGROUND: A prospective study was conducted in human immunodeficiency virus
      (HIV)-infected patients as they undergo alterations in their antiretroviral
      therapy (ART) to determine the effect of ART on autonomic function. METHODS: HIV
      infected subjects who were either 1) naive to ART and initiating ART, or 2)
      receiving ART and in HIV virologic failure for at least 4 months and were about
      to switch ART were enrolled in this study. Autonomic function assessment
      (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4
      months after initiating the new ART. Changes in clinical autonomic symptoms and
      virologic assessment were assessed. RESULTS: Twelve subjects completed the study:
      92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non
      Hispanic. Seventy-five percent were ART naive while 25% were failing their ART
      regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm(3). All subjects
      achieved an undetectable HIV viral load by the 4-month follow-up visit. The
      majority of naive subjects were started on an ART regimen of tenofovir /
      emtricitabine / efavirenz. There were no significant differences in autonomic
      function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests,
      with regards to ART initiation. CONCLUSION: This is the first study to examine
      the effects of initiating ART on autonomic function in early HIV infection. This
      study found no appreciable differences of ART on the autonomic nervous system
      when ART is initiated early in the course of HIV disease. ART may not contribute
      to short-term changes in autonomic function.

PMID- 22859900
TI  - Frequency of pulmonary hypertension in patients with COPD due to biomass smoke
      and tobacco smoke.
AB  - OBJECTIVES: Pulmonary hypertension (PH) is a common and well established
      complication of chronic obstructive pulmonary disease (COPD). Its presence is
      associated with decreased survival. This study was designed to investigate the PH
      frequency and its relations in hospitalized tobacco and biomass related COPD
      patients. METHODS AND RESULTS: The study was a retrospective review of inpatients
      with COPD defined as a history of tobacco or biomass smoking, Pulmonary function
      tests (PFT) within stable status, an echocardiogram within stable status. PH was
      defined as systolic pulmonary artery pressure (sPAP) >35 mmHg. Of the 694
      individuals, 600 had suitable aspects for inclusion of study. All Females were
      biomass exposer and males were tobacco smoker. The Prevalence of PH was found
      more frequent in females than males. It was more prominent in moderate level COPD
      cases (56,2% and 37,5%, P<0,002). Both groups had airflow limitation, hypercapnia
      and hypoxemia, but no differences were found in terms of PaCO(2) and PaO2.
      However, FEV1 % was lower in males than females (p<0,005). On the other hand, FVC
      % was lower in the females compared with the males (p < 0.02). When analyzing the
      influence of PFT and demographic parameters on PH in separate COPD level groups,
      the results a bit varied among the groups. CONCLUSION: Our study demonstrated
      that PH frequency is higher in female COPD cases due to biomass smoke than in
      male COPD cases due to tobacco smoke. The influence of FVC % on the risk of a
      person having PH increased with increasing COPD level.

PMID- 22859901
TI  - MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model
      with ischemia-reperfusion injury by suppressing cell apoptosis.
AB  - OBJECTIVE: To determine the role of microRNA 21(miR-21) on left ventricular
      remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate
      the underlying mechanism of miR-21 mediated myocardium protection. METHODS: Rats
      were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP
      group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery
      group. Changes in hemodynamic parameters were recorded at 1 week after I/R.
      Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left
      ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type I,
      type III and PCNA positive cells were measured. Primary cultures of neonatal rat
      cardiac ventricular myocytes were performed and cell ischemic injury was induced
      by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R). MiR-21
      inhibitor and pre-miR-21 were respectively added to the culture medium for the
      miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine
      the miR-21 levels in cultured cells. Flow cytometry was performed to examine the
      cell apoptosis. RESULTS: In the Ad-miR-21 group, LV dimensions, myocardial
      infarct size, LV/BW, collagen type I, type III and PCNA positive cells all
      significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the
      Ad-miR-21 significantly improved LVSP, LV +dp/dt(max), LV - dp/dt(min), and
      decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with
      the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21
      group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR
      21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis.
      CONCLUSIONS: Ad-miR-21 improves LV remodeling and decreases the apoptosis of
      myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions
      in protecting against I/R injury.

PMID- 22859902
TI  - Management of chronic pain of cervical disc herniation and radiculitis with
      fluoroscopic cervical interlaminar epidural injections.
AB  - STUDY DESIGN: A randomized, double-blind, active controlled trial. OBJECTIVE: To
      evaluate the effectiveness of cervical interlaminar epidural injections of local
      anesthetic with or without steroids in the management of chronic neck pain and
      upper extremity pain in patients with disc herniation and radiculitis. SUMMARY OF
      BACKGROUND DATA: Epidural injections in managing chronic neck and upper extremity
      pain are commonly employed interventions. However, their long-term effectiveness,
      indications, and medical necessity, of their use and their role in various
      pathologies responsible for persistent neck and upper extremity pain continue to
      be debated, even though, neck and upper extremity pain secondary to disc
      herniation and radiculitis, is described as the common indication. There is also
      paucity of high quality literature. METHODS: One-hundred twenty patients were
      randomly assigned to one of 2 groups: Group I patients received cervical
      interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL);
      Group II patients received 0.5% lidocaine, 4 mL, mixed with 1 mL of
      nonparticulate betamethasone. Primary outcome measure was >= 50 improvement in
      pain and function. Outcome assessments included Numeric Rating Scale (NRS),
      Oswestry Disability Index (ODI), opioid intake, employment, and changes in
      weight. RESULTS: Significant pain relief and functional status improvement (>=
      50%) was demonstrated in 72% of patients who received local anesthetic only and
      68% who received local anesthetic and steroids. In the successful group of
      participants, significant improvement was illustrated in 77% in local anesthetic
      group and 82% in local anesthetic with steroid group. CONCLUSIONS: Cervical
      interlaminar epidural injections with or without steroids may provide significant
      improvement in pain and function for patients with cervical disc herniation and
      radiculitis.

PMID- 22859903
TI  - Sofnolime with different water content causes different effects in two
      sevoflurane inhalational induction techniques with respect to the output of
      compound-A.
AB  - OBJECTIVE: During sevoflurane anesthesia with Sofnolime for CO(2) absorption, the
      factors affecting the production of compound A (a chemical is nepherotoxic) are
      still not clear. This study is designed to investigate the effects of different
      fresh gas flow during induction, the vital capacity induction (VCI) vs. the tidal
      volume breath induction (TBI) on the compound-A production with a fresh Sofnolime
      or a dehydrated Sofnolime using a simulated lung model. METHOD: The experiments
      were randomly divided into four groups: group one, VCIf, vital capacity fresh gas
      inflow with fresh Sofnolime; group two, TBIf, tidal volume breath fresh gas
      inflow with fresh Sofnolime; group three, VCId, vital capacity fresh gas inflow
      with dehydrated Sofnolime, and group four, TBId, tidal volume breath fresh gas
      inflow with dehydrated Sofnolime. The inspired sevoflurane was maintained at 8%,
      the concentrations of compound-A were assayed using Gas-spectrum technique, and
      Sofnolime temperatures were monitored at 1-min intervals throughout the
      experiment. RESULTS: The mean and maximum concentrations of compound A were
      significantly higher in the vital capacity group than the tidal volume breath
      group (P<0.01). At the beginning of anesthesia maintenance, the compound-A
      concentration in group VCIf was 36.28+/-6.13 ppm, which was significantly higher
      than the 27.32+/-4.21 ppm observed in group TBIf (P<0.01). However, these values
      decreased to approximately 2 ppm in the dehydrated Sofnolime groups. Sofnolime
      temperatures increased rapidly in the dehydrated Sofnolime groups but slowly in
      the fresh Sofnolime groups. CONCLUSION: With fresh Sofnolime, vital capacity
      induction increased compound-A production in the circuit system compared with
      tidal volume breath induction. However, with dehydrated Sofnolime, the effects of
      the two inhalation induction techniques on compound-A output were not
      significantly different.

PMID- 22859905
TI  - Notch signaling pathway and human placenta.
AB  - Notch signaling was evolutionarily conserved and critical for cell-fate
      determination, differentiation and many other biological processes. Growing
      evidences suggested that Notch signaling pathway played an important role in the
      mammalian placental development. All of the mammalian Notch family proteins had
      been identified in human placenta except Delta-like 3, which appeared to affect
      the axial skeletal system. However the molecular mechanisms that regulated the
      Notch signaling pathway remained largely unknown in human placenta. Therefore,
      additional research was needed to investigate expression pattern of Notch family
      members and the mechanisms for activation of Notch signaling pathway in human
      placenta, which might help elucidate the roles of Notch signaling pathway in
      human placentation. This review would focus on the roles of Notch receptors and
      ligands in the human placental trophoblasts function and placental angiogenesis.
      It might hopefully provide perspectives for future research about human
      placentation of pregnancy complicated by preeclampsia and other placenta
      associated diseases.

PMID- 22859904
TI  - Aspirin- and clopidogrel-associated bleeding complications: data mining of the
      public version of the FDA adverse event reporting system, AERS.
AB  - OBJECTIVE: Adverse event reports (AERs) submitted to the US Food and Drug
      Administration (FDA) were reviewed to assess the bleeding complications induced
      by the administration of antiplatelets and to attempt to determine the rank-order
      of the association. METHODS: After a deletion of duplicated submissions and the
      revision of arbitrary drug names, AERs involving warfarin, aspirin, cilostazol,
      clopidogrel, ethyl icosapentate, limaprost alfadex, sarpogrelate, and ticlopidine
      were analyzed. Authorized pharmacovigilance tools were used for the quantitative
      detection of signals, i.e., drug-associated adverse events, including the
      proportional reporting ratio, the reporting odds ratio, the information component
      given by a Bayesian confidence propagation neural network, and the empirical
      Bayes geometric mean. RESULTS: Based on 22,017,956 co-occurrences, i.e., drug
      adverse event pairs, found in 1,644,220 AERs from 2004 to 2009, 736 adverse
      events were listed as warfarin-associated adverse events, and 147 of the 736 were
      bleeding complications, including haemorrhage and haematoma. Both aspirin and
      clopidogrel were associated with haemorrhage, but the association was more
      noteworthy for clopidogrel. As for bleeding complications related to the
      gastrointestinal system, e.g., melaena and haematochezia, the statistical metrics
      suggested a stronger association for aspirin than clopidogrel. The total number
      of co-occurrences was not large enough to compare the association with bleeding
      complications for the other 5 antiplatelets. CONCLUSIONS: The data strongly
      suggest the necessity of well-organized clinical studies with respect to
      antiplatelet-associated bleeding complications.

PMID- 22859906
TI  - Symptomatic venous thromboembolism is a disease related to infection and immune
      dysfunction.
AB  - The characteristics of human genomics and cellular immune function between
      clinically symptomatic venous thromboembolism (VTE) and controls were
      systematically compared to explore the immunologic pathogenesis of VTE.
      Microarray assay showed the mRNA expressions of genes related to non-specific
      cellarer immune and cytokines were significantly down-regulated. Abnormal
      expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+
      ratio were detected in 54 among 56 patients. In PE patients, microarray assay
      revealed the imbalance in the expressions of genes related to the immune system.
      The expressions of genes related to non-specific immune cells and cytokines were
      markedly up-regulated and those associated with cellular immune were dramatically
      down-regulated. In VTE patients, cytological examination indicated the functions
      of NK cells were significantly compromised, and the antigen recognition and
      killing function of T cells markedly decreased. The consistence between genomic
      and cytological examination suggests the symptomatic VTE is closely associated
      with the infection and immune dysfunction.

PMID- 22859907
TI  - Rap system of stress stimulation can promote bone union after lower tibial bone
      fracture: a clinical research.
AB  - BACKGROUND: Lower tibial bone fracture may easily cause bone delayed union or
      nonunion because of lacking of dynamic mechanical load. OBJECTIVE: Research Group
      would design a new instrument as Rap System of Stress Stimulation (RSSS) to
      provide dynamic mechanical load which would promote lower tibial bone union
      postoperatively. METHODS: This clinical research was conducted from January 2008
      to December 2010, 92 patients(male 61/female 31, age 16-70 years, mean 36.3
      years) who suffered lower tibial bone closed fracture were given intramedullary
      nail fixation and randomly averagely separated into experimental group and
      control group(according to the successively order when patients went for the
      admission procedure). Then researchers analysed the clinical healing time, full
      weight bearing time, VAS (Visual Analogue Scales) score and callus growth score
      of Lane-Sandhu in 3,6,12 months postoperatively. The delayed union and nonunion
      rates were compared at 6 and 12 months separately. RESULTS: All the 92 patients
      had been followed up (mean 14 months). Clinical bone healing time in experimental
      group was 88.78+/-8.80 days but control group was 107.91+/-9.03 days. Full weight
      bearing time in experimental group was 94.07+/-9.81 days but control group was
      113.24+/-13.37 days respectively (P<0.05). The delayed union rate in 6 months was
      4.3% in experimental group but 10.9% in control group(P<0.05). The nonunion rate
      in 12 months was 6.5% in experimental group but 19.6% in control group(P<0.05).
      In 3, 6, 12 months postoperatively, VAS score and Lane-Sandhu score in
      experimental group had more significantly difference than them in control group.
      CONCLUSIONS: RSSS can intermittently provide dynamic mechanical load and
      stimulate callus formation, promote lower tibial bone union, reduce bone delayed
      union or nonunion rate. It is an adjuvant therapy for promoting bone union after
      lower tibial bone fracture.

PMID- 22859908
TI  - Chromatin proteins: key responders to stress.
AB  - Environments can be ever-changing and stresses are commonplace. In order for
      organisms to survive, they need to be able to respond to change and adapt to new
      conditions. Fortunately, many organisms have systems in place that enable dynamic
      adaptation to immediate stresses and changes within the environment. Much of this
      cellular response is coordinated by modulating the structure and accessibility of
      the genome. In eukaryotic cells, the genome is packaged and rolled up by histone
      proteins to create a series of DNA/histone core structures known as nucleosomes;
      these are further condensed into chromatin. The degree and nature of the
      condensation can in turn determine which genes are transcribed. Histones can be
      modified chemically by a large number of proteins that are thereby responsible
      for dynamic changes in gene expression. In this Primer we discuss findings from a
      study published in this issue of PLoS Biology by Weiner et al. that highlight how
      chromatin structure and chromatin binding proteins alter transcription in
      response to environmental changes and stresses. Their study reveals the
      importance of chromatin in mediating the speed and amplitude of stress responses
      in cells and suggests that chromatin is a critically important component of the
      cellular response to stress.

PMID- 22859909
TI  - Musical melody and speech intonation: singing a different tune.
AB  - Music and speech are often cited as characteristically human forms of
      communication. Both share the features of hierarchical structure, complex sound
      systems, and sensorimotor sequencing demands, and both are used to convey and
      influence emotions, among other functions [1]. Both music and speech also
      prominently use acoustical frequency modulations, perceived as variations in
      pitch, as part of their communicative repertoire. Given these similarities, and
      the fact that pitch perception and production involve the same peripheral
      transduction system (cochlea) and the same production mechanism (vocal tract), it
      might be natural to assume that pitch processing in speech and music would also
      depend on the same underlying cognitive and neural mechanisms. In this essay we
      argue that the processing of pitch information differs significantly for speech
      and music; specifically, we suggest that there are two pitch-related processing
      systems, one for more coarse-grained, approximate analysis and one for more fine
      grained accurate representation, and that the latter is unique to music. More
      broadly, this dissociation offers clues about the interface between sensory and
      motor systems, and highlights the idea that multiple processing streams are a
      ubiquitous feature of neuro-cognitive architectures.

PMID- 22859910
TI  - Researching new methods of screening for adverse pregnancy outcome: lessons from
      pre-eclampsia.

PMID- 22859912
TI  - Medical device regulation: time to improve performance.

PMID- 22859911
TI  - Risk of venous thromboembolism in patients with cancer: a systematic review and
      meta-analysis.
AB  - BACKGROUND: People with cancer are known to be at increased risk of venous
      thromboembolism (VTE), and this risk is believed to vary according to cancer
      type, stage of disease, and treatment modality. Our purpose was to summarise the
      existing literature to determine precisely and accurately the absolute risk of
      VTE in cancer patients, stratified by malignancy site and background risk of VTE.
      METHODS AND FINDINGS: We searched the Medline and Embase databases from 1 January
      1966 to 14 July 2011 to identify cohort studies comprising people diagnosed with
      one of eight specified cancer types or where participants were judged to be
      representative of all people with cancer. For each included study, the number of
      patients who developed clinically apparent VTE, and the total person-years of
      follow-up were extracted. Incidence rates of VTE were pooled across studies using
      the generic inverse variance method. In total, data from 38 individual studies
      were included. Among average-risk patients, the overall risk of VTE was estimated
      to be 13 per 1,000 person-years (95% CI, 7 to 23), with the highest risk among
      patients with cancers of the pancreas, brain, and lung. Among patients judged to
      be at high risk (due to metastatic disease or receipt of high-risk treatments),
      the risk of VTE was 68 per 1,000 person-years (95% CI, 48 to 96), with the
      highest risk among patients with brain cancer (200 per 1,000 person-years; 95%
      CI, 162 to 247). Our results need to be considered in light of high levels of
      heterogeneity, which exist due to differences in study population, outcome
      definition, and average duration of follow-up between studies. CONCLUSIONS: VTE
      occurs in greater than 1% of cancer patients each year, but this varies widely by
      cancer type and time since diagnosis. The absolute VTE risks obtained from this
      review can aid in clinical decision-making about which people with cancer should
      receive anticoagulant prophylaxis and at what times.

PMID- 22859913
TI  - Digital humanitarianism: collective intelligence emerging.

PMID- 22859914
TI  - Surveillance of infection severity: a registry study of laboratory diagnosed
      Clostridium difficile.
AB  - BACKGROUND: Changing clinical impact, as virulent clones replace less virulent
      ones, is a feature of many pathogenic bacterial species and can be difficult to
      detect. Consequently, innovative techniques monitoring infection severity are of
      potential clinical value. METHODS AND FINDINGS: We studied 5,551 toxin-positive
      and 20,098 persistently toxin-negative patients tested for Clostridium difficile
      infection between February 1998 and July 2009 in a group of hospitals based in
      Oxford, UK, and investigated 28-day mortality and biomarkers of inflammation
      (blood neutrophil count, urea, and creatinine concentrations) collected at
      diagnosis using iterative sequential regression (ISR), a novel joinpoint-based
      regression technique suitable for serial monitoring of continuous or dichotomous
      outcomes. Among C. difficile toxin-positive patients in the Oxford hospitals,
      mean neutrophil counts on diagnosis increased from 2003, peaked in 2006-2007, and
      then declined; 28-day mortality increased from early 2006, peaked in late 2006
      2007, and then declined. Molecular typing confirmed these changes were likely due
      to the ingress of the globally distributed severe C. difficile strain, ST1. We
      assessed the generalizability of ISR-based severity monitoring in three ways.
      First, we assessed and found strong (p<0.0001) associations between isolation of
      the ST1 severe strain and higher neutrophil counts at diagnosis in two unrelated
      large multi-centre studies, suggesting the technique described might be useful
      elsewhere. Second, we assessed and found similar trends in a second group of
      hospitals in Birmingham, UK, from which 5,399 cases were analysed. Third, we used
      simulation to assess the performance of this surveillance system given the
      ingress of future severe strains under a variety of assumptions. ISR-based
      severity monitoring allowed the detection of the severity change years earlier
      than mortality monitoring. CONCLUSIONS: Automated electronic systems providing
      early warning of the changing severity of infectious conditions can be
      established using routinely collected laboratory hospital data. In the settings
      studied here these systems have higher performance than those monitoring
      mortality, at least in C. difficile infection. Such systems could have wider
      applicability for monitoring infections presenting in hospital.

PMID- 22859917
TI  - A Combined Group and Individual 12-Step Facilitative Intervention Targeting
      Stimulant Abuse in the NIDA Clinical Trials Network: STAGE-12.

PMID- 22859915
TI  - Assessing drug target association using semantic linked data.
AB  - The rapidly increasing amount of public data in chemistry and biology provides
      new opportunities for large-scale data mining for drug discovery. Systematic
      integration of these heterogeneous sets and provision of algorithms to data mine
      the integrated sets would permit investigation of complex mechanisms of action of
      drugs. In this work we integrated and annotated data from public datasets
      relating to drugs, chemical compounds, protein targets, diseases, side effects
      and pathways, building a semantic linked network consisting of over 290,000 nodes
      and 720,000 edges. We developed a statistical model to assess the association of
      drug target pairs based on their relation with other linked objects. Validation
      experiments demonstrate the model can correctly identify known direct drug target
      pairs with high precision. Indirect drug target pairs (for example drugs which
      change gene expression level) are also identified but not as strongly as direct
      pairs. We further calculated the association scores for 157 drugs from 10 disease
      areas against 1683 human targets, and measured their similarity using a [Formula:
      see text] score matrix. The similarity network indicates that drugs from the same
      disease area tend to cluster together in ways that are not captured by structural
      similarity, with several potential new drug pairings being identified. This work
      thus provides a novel, validated alternative to existing drug target prediction
      algorithms. The web service is freely available at: http://chem2bio2rdf.org/slap.

PMID- 22859918
TI  - CIBIC Plus-J Assessment Using a Videotaped Method in Alzheimer's Disease
      Patients.
AB  - BACKGROUND/AIMS: CIBIC plus-J is the Japanese language version equivalent to
      CIBIC plus. Variability of CIBIC plus-J arises among raters in accordance with
      their experience and their memories of patients' conditions at baseline.
      Therefore, in a multicenter trial of Alzheimer's disease, CIBIC plus-J interviews
      with Alzheimer's disease patients were videotaped, and the tapes were assessed by
      central raters as a means to improve the reliability of CIBIC plus-J assessment.
      METHODS: Two of eight central raters were randomly selected and independently
      assessed the CIBIC plus-J of each patient. RESULTS: CIBIC plus-J of 41 patients
      was assessed. The agreement rate between the two raters was 46.3% (19/41), when
      two raters assessed the CIBIC plus-J of the same patient. However, when
      considering disagreement between adjacent points as 'agree', the agreement rate
      was 97.6% (40/41). Although the kappa coefficients contained coincidence, simple
      and quadratic weighted kappa coefficients [95% confidential interval (CI)] were
      0.226 (0.066-0.386) and 0.633 (0.507-0.759), respectively, and when considering
      disagreement between adjacent points as 'agree', the agreement kappa was 0.896
      (0.752-1.041). The interclass coefficient from the two-way layout model was
      0.639. CONCLUSION: The reliability of the CIBIC plus-J assessment with the
      videotaped method was acceptable.

PMID- 22859919
TI  - Hepatobiliary transport in health and disease.
AB  - Bile salts, cholesterol and phosphatidylcholine are secreted across the
      canalicular membrane of hepatocytes into bile by ATP-binding cassette (ABC)
      transporters. Secretion of bile salts by ABCB11 is essential for bile flow and
      for absorption of lipids and fat-soluble vitamins. ABCG5 and ABCG8 eliminate
      excess cholesterol and sterols from the body by secreting them into bile. There
      are two mechanisms to protect the canalicular membrane from solubilization by
      bile salts; ABCB4 secretes phosphatidylcholine into bile to form mixed micelles
      with bile salts, and ATP8B1 maintains the canalicular membrane in a liquid
      ordered state. Three different forms of progressive familial intrahepatic
      cholestasis (PFIC) disorders, PFIC1, PFIC2 and PFIC3, are caused by mutations in
      ATP8B1, ABCB11 and ABCB4, respectively. Sitosterolemia is caused by mutations in
      ABCG5 and ABCG8. This article reviews the physiological roles of these
      canalicular transporters, and the pathophysiological processes and clinical
      features associated with their mutations.

PMID- 22859920
TI  - The role of biologic agents in damage progression in rheumatoid arthritis:
      indirect comparison of data coming from randomized clinical trials.
AB  - OBJECTIVES: All biologic agents approved for the treatment of rheumatoid
      arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage
      progression in several randomized clinical trials (RCTs), but direct head-to-head
      comparisons have never been conducted. The purpose of this investigation is to
      analyse data coming from main RA RCTs and to perform an indirect comparison.
      METHODS: A systematic review of literature from 1988 to 2011 was conducted. Only
      randomized, double-blind, controlled, comparative trials, with evaluation of
      radiographic progression were included. The radiographic score was standardized
      and mean difference in the percentage of the annual radiographic progression rate
      was used as the effect measure. Heterogeneity between studies was estimated by
      I(2) test. For each trial, the effect was plotted according to its standard error
      in a funnel plot. RESULTS: Of 44 potentially relevant trials, 12 RCTs were
      included in the study. In order to optimize RCTs comparison, studies were
      stratified in early and late RA group. Main population characteristics were
      similar in both early and late RA groups, whereas the standardized baseline
      radiographic score value significantly differs among trials in both early (range
      2.7-21.9) and late (range 23.46-75) RA groups. The standardized annual estimated
      progression is similar across the late RA group. Strong evidence of heterogeneity
      (I(2) = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the
      early RA group. Total mean difference was -16.28 (95% confidence interval [CI] 
      24.42 to -8.14). For the late RA group a random model was used (I(2) = 99%, p =
      0.00001) and a total mean difference of -39.25 (95% CI -53.77 to -24.73) was
      found. CONCLUSIONS: All biologic agents provide a favourable effect on disease
      progression both in early and late RA. The significant heterogeneity among
      various RCTs did not allow an effective comparison of the performance of biologic
      agents in each study.

PMID- 22859921
TI  - The role of RANK ligand/osteoprotegerin in rheumatoid arthritis.
AB  - In the complex system of bone remodeling, the receptor activator of nuclear
      factor kappaB ligand (RANKL)/osteoprotegerin (OPG) pathway is the coupling factor
      between bone formation and bone resorption. RANKL binds to the RANK receptor of
      pre-osteoclasts and mature osteoclasts and stimulates their activation and
      differentiation. The production of RANKL/OPG by osteoblasts is influenced by
      hormones, growth factors and cytokines, which each have a different effect on the
      production of RANKL and OPG. Ultimately, the balance between RANKL and OPG
      determines the degree of proliferation and activity of the osteoclasts. In
      rheumatoid arthritis (RA), bone erosions are the result of osteoclastic bone
      resorption at the sites of synovitis, where RANKL expression is also found.
      Furthermore, magnetic resonance imaging (MRI) bone edema in RA indicates the
      presence of active inflammation within bone and the presence of osteitis, which
      is also associated with the expression of RANKL. Bone loss has been documented in
      the cortical and trabecular bone in the joints of the hand of RA patients. Both
      synovitis and periarticular bone involvement (osteitis and bone loss) are
      essential components of RA: they occur early in the disease and both are
      predictive for the occurrence and progression of bone damage. RANKL knockout mice
      and mice treated with OPG did not develop focal bone loss, in spite of persistent
      joint inflammation. Inhibition of osteoclasts by denosumab, a humanized antibody
      that selectively binds RANKL, has revealed in patients with RA that the
      occurrence of erosions and periarticular bone loss can be halted, however without
      affecting synovial inflammation. This disconnect between inflammation and bone
      destruction opens new ways to separately focus treatment on inflammation and
      osteoclastogenesis for preventing and/or minimizing the connection between joints
      and subchondral bone and bone marrow.

PMID- 22859923
TI  - Biologicals and bone loss.
AB  - Inflammatory joint diseases are associated with extra-articular side effects
      including bone involvement.There is an increased risk of osteoporotic fractures.
      The pathogeneses of local and generalized bone loss share a common pathway. Early
      and active rheumatoid arthritis is associated with longitudinal observed bone
      loss and fracture rate is of vertebral and nonvertebral fractures is doubled
      compared with matched healthy controls. Lowering disease activity with TNF
      inhibitors or is associated with stabilisation of bone mineral density by
      counteracting elevated bone resorption.

PMID- 22859922
TI  - Assessment of synovitis to predict bone erosions in rheumatoid arthritis.
AB  - Although rheumatoid arthritis (RA) is traditionally considered as the prototype
      of destructive arthritis, the course of the disease varies considerably, with
      some patients experiencing more rapid progression of joint damage and disability
      than others. Given the increasing availability of treatment targets and options,
      timely recognition of individual's outcomes could allow therapeutic allocation
      according to personalized benefit-risk profiles. Research efforts are thus
      increasingly focused at discovering predictive markers that could identify
      patients with aggressive, rapidly progressive disease and poor prognosis. As
      joint destruction in RA is the result of the cumulative burden of inflammation,
      variables reflecting the severity of synovitis and its persistence over time
      might refine our ability to build early prognostic algorithms. The goal of this
      article is to review the clinical implications of the assessment of synovitis in
      relation to radiographic outcomes. Traditional and novel assessment tools will be
      discussed, including clinical measures, imaging techniques and tissue biomarkers.
      Achievements in the field of synovial tissue analysis and peripheral blood
      biomarkers of synovitis represent only the first steps of ongoing progress, which
      still need to be integrated into the phenotypic heterogeneity of RA.

PMID- 22859924
TI  - Alterations in periarticular bone and cross talk between subchondral bone and
      articular cartilage in osteoarthritis.
AB  - The articular cartilage and the subchondral bone form a biocomposite that is
      uniquely adapted to the transfer of loads across the diarthrodial joint. During
      the evolution of the osteoarthritic process biomechanical and biological
      processes result in alterations in the composition, structure and functional
      properties of these tissues. Given the intimate contact between the cartilage and
      bone, alterations of either tissue will modulate the properties and function of
      the other joint component. The changes in periarticular bone tend to occur very
      early in the development of OA. Although chondrocytes also have the capacity to
      modulate their functional state in response to loading, the capacity of these
      cells to repair and modify their surrounding extracellular matrix is relatively
      limited in comparison to the adjacent subchondral bone. This differential
      adaptive capacity likely underlies the more rapid appearance of detectable
      skeletal changes in OA in comparison to the articular cartilage. The OA changes
      in periarticular bone include increases in subchondral cortical bone thickness,
      gradual decreases in subchondral trabeular bone mass, formation of marginal joint
      osteophytes, development of bone cysts and advancement of the zone of calcified
      cartilage between the articular cartilage and subchondral bone. The expansion of
      the zone of calcified cartilage contributes to overall thinning of the articular
      cartilage. The mechanisms involved in this process include the release of soluble
      mediators from chondrocytes in the deep zones of the articular cartilage and/or
      the influences of microcracks that have initiated focal remodeling in the
      calcified cartilage and subchondral bone in an attempt to repair the microdamage.
      There is the need for further studies to define the pathophysiological mechanisms
      involved in the interaction between subchondral bone and articular cartilage and
      for applying this information to the development of therapeutic interventions to
      improve the outcomes in patients with OA.

PMID- 22859925
TI  - Clinical significance of bone changes in osteoarthritis.
AB  - Osteoarthritis (OA), the most common form of arthritis, is now understood to
      involve all joint tissues, with active anabolic and catabolic processes. Knee OA
      in particular is considered to be a largely mechanically-driven disease. As bone
      adapts to loads by remodeling to meet its mechanical demands, bone alterations
      likely play an important role in OA development. Subchondral bone changes in bone
      turnover, mineralization, and volume result in altered apparent and material
      density of bone that may adversely affect the joint's biomechanical environment.
      Subchondral bone alterations such as bone marrow lesions (BMLs) and subchondral
      bone attrition (SBA) both tend to occur more frequently in the more loaded knee
      compartments, and are associated with cartilage loss in the same region.
      Recently, MRI-based 3D bone shape has been shown to track concurrently with and
      predict OA onset.The contributions of structural abnormalities to the clinical
      manifestations of knee OA are becoming better understood as well. While a
      structure-symptom discordance in knee OA is thought to exist, such observations
      do not take into account all potential factors that can contribute to between
      person differences in the pain experience. Using novel methodology, pain
      fluctuation has been associated with changes in BMLs, synovitis and effusion. SBA
      has also been associated with knee pain, but the relationship of osteophytes to
      pain has been conflicting.Understanding the pathophysiologic sequences and
      consequences of OA pathology will guide rational therapeutic targeting.
      Importantly, rational treatment targets require understanding what structures
      contribute to pain as pain is the reason patients seek medical care.

PMID- 22859927
TI  - The epidemiology of osteoporosis and fractures in ankylosing spondylitis.
AB  - Bone is a target in many inflammatory rheumatic diseases. Inflammation leads to a
      wide range of changes in bone, and especially bone remodeling. In ankylosing
      spondylitis (AS) bone loss has been documented, but measuring bone density in the
      spine is hampered by new bone formation in syndesmophytes, periost and within the
      vertebrae. The risk of vertebral fractures is increased in AS. The diagnosis of
      vertebral fractures requires imaging and adequate evaluation of vertebral
      heights. In addition, in the ankysosed spine segments, additional imaging is
      often needed to diagnose spinal fractures at unusual locations (cervical spine)
      or in the posterior arch structures. Risk factors for vertebral fractures are
      helpful for case finding. Fracture prevention is indicated in high risk patients
      with AS, especially when they have already a vertebral fracture or in the
      presence of osteoporosis.

PMID- 22859926
TI  - Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism
      in health and osteoarthritis.
AB  - Chondrogenesis occurs as a result of mesenchymal cell condensation and
      chondroprogenitor cell differentiation. Following chondrogenesis, the
      chondrocytes remain as resting cells to form the articular cartilage or undergo
      proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis
      in a process termed endochondral ossification, whereby the hypertrophic cartilage
      is replaced by bone. Human adult articular cartilage is a complex tissue of
      matrix proteins that varies from superficial to deep layers and from loaded to
      unloaded zones. A major challenge to efforts to repair cartilage by stem cell
      based and other tissue-engineering strategies is the inability of the resident
      chondrocytes to lay down a new matrix with the same properties as it had when it
      was formed during development. Thus, understanding and comparing the mechanisms
      of cartilage remodeling during development, osteoarthritis (OA), and aging may
      lead to more effective strategies for preventing cartilage damage and promoting
      repair. The pivotal proteinase that marks OA progression is matrix
      metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase,
      which is regulated by both stress and inflammatory signals. We and other
      investigators have found that there are common mediators of these processes in
      human OA cartilage. We also observe temporal and spatial expression of these
      mediators in early through late stages of OA in mouse models and are analyzing
      the consequences of knockout or transgenic overexpression of critical genes.
      Since the chondrocytes in adult human cartilage are normally quiescent and
      maintain the matrix in a low turnover state, understanding how they undergo
      phenotypic modulation and promote matrix destruction and abnormal repair in OA
      may to lead to identification of critical targets for therapy to block cartilage
      damage and promote effective cartilage repair.

PMID- 22859928
TI  - The role of bone morphogenetic proteins in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS), the best-known form of spondyloarthritis (SpA), is a
      remodelling arthritis characterized by chronic inflammation and bone formation.
      Ankylosis of the axial skeleton and sacroiliac joints leads to an impairment of
      spinal mobility, progressive spinal fusion and an increased risk of spinal
      fractures. The nature of the relationship between inflammation and new bone
      formation in AS has been controversial and questions remain as to whether there
      is a direct relationship between inflammation and new bone formation. Like
      others, we have hypothesized that the molecular pathways underlying ankylosis
      recapitulate the process of endochondral bone formation and that bone
      morphogenetic proteins (BMPs) play a key role in this process in AS. Furthermore,
      we discuss the entheseal stress hypothesis, which proposes that inflammation and
      ankylosis are linked but largely independent processes, and consider observations
      from mouse models and other human diseases which also imply that biomechanical
      factors contribute to the pathogenesis of AS. As current therapeutics, such as
      tumour necrosis factor inhibitors do not impede disease progression and ankylosis
      in AS, it is the pathways discussed in this review that are the now the focus for
      the identification of future drug targets.

PMID- 22859929
TI  - Imaging in ankylosing spondylitis.
AB  - Imaging is an integral part of the management of patients with ankylosing
      spondylitis and axial spondyloarthritis. Characteristic radiographic and/or
      magnetic resonance imaging (MRI) findings are key in the diagnosis. Radiography
      and MRI are also useful in monitoring the disease. Radiography is the
      conventional, albeit quite insensitive, gold standard method for assessment of
      structural damage in spine and sacroiliac joints, whereas MRI has gained a
      decisive role in monitoring disease activity in clinical trials and practice. MRI
      may also, if ongoing research demonstrates a sufficient reliability and
      sensitivity to change, become a new standard method for assessment of structural
      damage. Ultrasonography allows visualization of peripheral arthritis and
      enthesitis, but has no role in the assessment of axial manifestations. Computed
      tomography is a sensitive method for assessment of structural changes in the
      spine and sacroiliac joints, but its clinical utility is limited due to its use
      of ionizing radiation and lack of ability to assess the soft tissues. It is
      exciting that with continued dedicated research and the rapid technical
      development it is likely that even larger improvements in the use of imaging may
      occur in the decade to come, for the benefit of our patients.

PMID- 22859930
TI  - The role of surfactant in respiratory distress syndrome.
AB  - The key feature of respiratory distress syndrome (RDS) is the insufficient
      production of surfactant in the lungs of preterm infants. As a result,
      researchers have looked into the possibility of surfactant replacement therapy as
      a means of preventing and treating RDS. We sought to identify the role of
      surfactant in the prevention and management of RDS, comparing the various types,
      doses, and modes of administration, and the recent development. A PubMed search
      was carried out up to March 2012 using phrases: surfactant, respiratory distress
      syndrome, protein-containing surfactant, protein-free surfactant, natural
      surfactant, animal-derived surfactant, synthetic surfactant, lucinactant,
      surfaxin, surfactant protein-B, surfactant protein-C.Natural, or animal-derived,
      surfactant is currently the surfactant of choice in comparison to protein-free
      synthetic surfactant. However, it is hoped that the development of protein
      containing synthetic surfactant, such as lucinactant, will rival the efficacy of
      natural surfactants, but without the risks of their possible side effects.
      Administration techniques have also been developed with nasal continuous positive
      airway pressure (nCPAP) and selective surfactant administration now recommended;
      multiple surfactant doses have also reported better outcomes. An aerosolised form
      of surfactant is being trialled in the hope that surfactant can be administered
      in a non-invasive way. Overall, the advancement, concerning the structure of
      surfactant and its mode of administration, offers an encouraging future in the
      management of RDS.

PMID- 22859931
TI  - Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and
      invasion of urothelial carcinoma cells.
AB  - The insulin-like growth factor receptor I (IGF-IR) plays an essential role in
      transformation by promoting cell growth and protecting cancer cells from
      apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in
      invasive bladder cancer tissues and promotes motility and invasion of urothelial
      carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent
      activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK)
      at dynamic focal adhesions and is critical for promoting motility of urothelial
      cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate
      paxillin activation; however, their role in regulating IGF-IR-dependent signaling
      and motility in bladder cancer has not been established. In this study we
      demonstrate that FAK was not required for IGF-IR-dependent signaling and motility
      of invasive urothelial carcinoma cells. On the contrary, Pyk2, which was strongly
      activated by IGF-I, was critical for IGF-IR-dependent motility and invasion and
      regulated IGF-I-dependent activation of the Akt and MAPK pathways. Using
      immunofluorescence and AQUA analysis we further discovered that Pyk2 was
      overexpressed in bladder cancer tissues as compared to normal tissue controls.
      Significantly, in urothelial carcinoma tissues there was increased Pyk2
      localization in the nuclei as compared to normal tissue controls. These results
      provide the first evidence of a specific Pyk2 activity in regulating IGF-IR
      dependent motility and invasion of bladder cancer cells suggesting that Pyk2 and
      the IGF-IR may play a critical role in the invasive phenotype in urothelial
      neoplasia. In addition, Pyk2 and the IGF-IR may serve as novel biomarkers with
      diagnostic and prognostic significance in bladder cancer.

PMID- 22859932
TI  - The transcriptional coactivators p/CIP and SRC-1 control insulin resistance
      through IRS1 in obesity models.
AB  - Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as
      transcriptional coactivators for nuclear hormone receptors and other
      transcription factors in vitro. In a previous study, we reported initial
      characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double
      knockout (DKO) mice, which exhibit increased energy expenditure, and suggested
      that nuclear hormone receptor target genes were involved in these phenotypes. In
      this study, we demonstrate that p/CIP and SRC1 control insulin signaling in a
      cell-autonomous manner both in vitro and in vivo. Genetic deletion of p/CIP and
      SRC-1 increases glucose uptake and enhances insulin sensitivity in both regular
      chow- and high fat diet-fed DKO mice despite increased food intake.
      Interestingly, we discover that loss of p/CIP and SRC-1 results in resistance to
      age-related obesity and glucose intolerance. We show that expression levels of a
      key insulin signaling component, insulin receptor substrate 1 (IRS1), are
      significantly increased in two cell lines representing fat and muscle lineages
      with p/CIP and SRC-1 deletions and in white adipose tissue and skeletal muscle of
      DKO mice; this may account for increased glucose metabolism and insulin
      sensitivity. This is the first evidence that the p160 coactivators control
      insulin signaling and glucose metabolism through IRS1. Therefore, our studies
      indicate that p/CIP and SRC-1 are potential therapeutic targets not only for
      obesity but also for diabetes.

PMID- 22859933
TI  - Bipolar disorder, brain-derived neurotrophic factor (BDNF) Val66Met polymorphism
      and brain morphology.
AB  - In this study of the effect of bipolar status and presence of BDNF Val66Met
      polymorphism on differences in regional brain volumes, we hypothesized based on
      previous studies that 1) bipolar subjects will have smaller regional brain
      volumes than healthy controls; 2) BDNF Met66 allele carriers within the same
      population are likely to have smaller regional brain volumes as compared to Val66
      homozygyotes. In our Caucasian sample of 166 bipolar subjects and 64 gender
      matched healthy controls, we found significant decreases in total (p = 0.005) and
      regional gray matter volumes in bipolar patients compared to healthy controls,
      more pronounced in the inferior and posterior parts of the brain, together with a
      concomitant increase in total CSF (p = 0.012) particularly in the lateral
      ventricles (p = 0.023). However, there was no difference in white matter volumes
      noted by other studies. Furthermore we did not find significant differences in
      other brain regions that have been reported by other authors. Nor did we find a
      significant effect of BDNF on these measurements.

PMID- 22859934
TI  - Discovering communities through friendship.
AB  - We introduce a new method for detecting communities of arbitrary size in an
      undirected weighted network. Our approach is based on tracing the path of closest
      friendship between nodes in the network using the recently proposed Generalized
      Erds Numbers. This method does not require the choice of any arbitrary parameters
      or null models, and does not suffer from a system-size resolution limit. Our
      closest-friend community detection is able to accurately reconstruct the true
      network structure for a large number of real world and artificial benchmarks, and
      can be adapted to study the multi-level structure of hierarchical communities as
      well. We also use the closeness between nodes to develop a degree of robustness
      for each node, which can assess how robustly that node is assigned to its
      community. To test the efficacy of these methods, we deploy them on a variety of
      well known benchmarks, a hierarchal structured artificial benchmark with a known
      community and robustness structure, as well as real-world networks of
      coauthorships between the faculty at a major university and the network of
      citations of articles published in Physical Review. In all cases,
      microcommunities, hierarchy of the communities, and variable node robustness are
      all observed, providing insights into the structure of the network.

PMID- 22859935
TI  - Reduced APOBEC3H variant anti-viral activities are associated with altered RNA
      binding activities.
AB  - APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying
      activities against retroviruses and retrotransposons. The A3H gene contains
      several single nucleotide polymorphisms and up to seven haplotypes have been
      detected in humans. Although variations in anti-viral function among A3H
      haplotypes are not fully understood, only 15N105R-containing A3H variants are
      known to have potent activities against Vif-deficient HIV-1. Unique motif
      RLYY(F/Y)W of APOBEC3G (A3G) and APOBEC3F (A3F) required for 7SL RNA binding and
      HIV-1 incorporation is also conserved in all A3H variants. Like A3G, A3H HapII
      also demonstrated high binding affinity to host small RNAs such as 7SL and Y
      RNAs. Mutation of a critical amino acid, W115A resulted in reduced expression
      level, decreased affinity for 7SL RNA, impairment of virion packaging and reduced
      anti-viral activity. By comparison, A3H HapI had lower binding affinities to host
      small RNAs and reduced efficiency of virion incorporation, resulting in
      significantly reduced anti-viral activity. The SNP DeltaN15 commonly found in A3H
      HapIII and HapIV abolished their abilities to associate with RNAs, and A3H
      HapIIDelta15N failed to package into HIV-1 virions or exhibited any anti-viral
      activity. Finally, we showed that A3H variants had distinct cellular localization
      patterns, which correlated with their different RNA binding affinities. Thus, Pol
      III RNA such as 7SL RNA binding is a conserved feature of potent anti-HIV human
      APOBEC3 cytidine deaminases.

PMID- 22859936
TI  - The -2518A/G polymorphism in the MCP-1 gene and tuberculosis risk: a meta
      analysis.
AB  - BACKGROUND: The -2518A/G polymorphism in the monocyte chemoattractant protein-1
      (MCP-1) gene has been implicated in the susceptibility to tuberculosis (TB), but
      the results are not conclusive. The aim of this study is to investigate the
      association between the -2518A/G polymorphism in the MCP-1 gene and the risk of
      tuberculosis by meta-analysis. METHODS: We searched Pubmed, Embase, CNKI and
      Wanfang databases, covering all studies until April 29(th), 2011. Statistical
      analyses were performed using the Revman4.2 and STATA10.0 software. RESULTS: A
      total of 5341 cases and 6075 controls in 13 case-control studies were included in
      the meta-analysis. The results indicated that the GG homozygote carriers had a
      67% increased risk of TB compared with the A allele carriers (GG vs. GA+AA: OR =
      1.67, 95%CI = 1.25-2.23, P = 0.0006). In the subgroup analysis by ethnicity,
      significant elevated risks were found in Asians and Latinos, but not in Africans
      (GG vs. GA+AA: OR = 1.79, 95%CI = 1.19-2.70 and P = 0.005 for Asians; OR = 2.15,
      95%CI = 1.32-3.51 and P = 0.002 for Latinos; OR = 1.28, 95%CI = 0.45-3.64 and P =
      0.65 for Africans). CONCLUSION: This meta-analysis suggested that the -2518A/G
      polymorphism of MCP-1 gene would be a risk factor for TB in Asians and Latinos,
      while not in Africans.

PMID- 22859937
TI  - Unique alterations of an ultraconserved non-coding element in the 3'UTR of ZIC2
      in holoprosencephaly.
AB  - Coding region alterations of ZIC2 are the second most common type of mutation in
      holoprosencephaly (HPE). Here we use several complementary bioinformatic
      approaches to identify ultraconserved cis-regulatory sequences potentially
      driving the expression of human ZIC2. We demonstrate that an 804 bp element in
      the 3' untranslated region (3'UTR) is highly conserved across the evolutionary
      history of vertebrates from fish to humans. Furthermore, we show that while
      genetic variation of this element is unexpectedly common among holoprosencephaly
      subjects (6/528 or >1%), it is not present in control individuals. Two of six
      proband-unique variants are de novo, supporting their pathogenic involvement in
      HPE outcomes. These findings support a general recommendation that the
      identification and analysis of key ultraconserved elements should be incorporated
      into the genetic risk assessment of holoprosencephaly cases.

PMID- 22859938
TI  - Endoplasmic reticulum stress stimulates p53 expression through NF-kappaB
      activation.
AB  - BACKGROUND: Induction of apoptosis by endoplasmic reticulum (ER) stress is
      implicated as the major factor in the development of multiple diseases. ER stress
      also appears to be a potentially useful major response to many chemotherapeutic
      drugs and environmental chemical compounds. A previous study has indicated that
      one major apoptotic regulator, p53, is significantly increased in response to ER
      stress, and participates in ER stress-induced apoptosis. However, the regulators
      of p53 expression during ER stress are still not fully understood. PRINCIPAL
      FINDINGS: In this report, we demonstrate that induction of p53 expression is
      mediated through NF-kappaB signaling pathways during ER stress in MCF-7 cells.
      Tunicamycin or brefeldin A, two ER stress inducers, increased p53 expression in
      MCF-7 and Hela cells. We found p53 nuclear localization, activity, and
      phosphorylation at serine 15 on p53 increased during ER stress. Nuclear
      translocation of NF-kappaB and activity of NF-kappaB were also observed during ER
      stress. ER stress-induced p53 expression was significantly inhibited by
      coincubation with the NF-kappaB inhibitor, Bay 11-7082 and downregulation of NF
      kappaB p65 expression. The role of p53 in mediating Brefeldin A-induced apoptosis
      was also investigated. Induction of p53 expression by Brefeldin A was correlated
      to Brefeldin A-induced apoptosis. Furthermore, downregulation of p53 expression
      by p53 siRNA significantly reduced Brefeldin A-induced apoptosis in MCF-7 cells.
      SIGNIFICANCE: Taken together, NF-kappaB activation and induction of p53
      expression is essential for ER stress-induced cell death which is important for
      therapeutic effects of clinical cancer drugs. Our results may provide insight
      into the mechanism of cancer chemotherapy efficacy that is associated with
      induction of ER stress.

PMID- 22859939
TI  - Sirolimus induced phosphaturia is not caused by inhibition of renal apical sodium
      phosphate cotransporters.
AB  - The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal
      tubule. Posttransplant phosphaturia is common and aggravated by sirolimus
      immunosuppression. The cause of sirolimus induced phosphaturia however remains
      elusive. Male Wistar rats received sirolimus or vehicle for 2 or 7 days
      (1.5mg/kg). The urine phosphate/creatinine ratio was higher and serum phosphate
      was lower in sirolimus treated rats, fractional excretion of phosphate was
      elevated and renal tubular phosphate reabsorption was reduced suggesting a renal
      cause for hypophosphatemia. PTH was lower in sirolimus treated rats. FGF 23
      levels were unchanged at day 2 but lower in sirolimus treated rats after 7 days.
      Brush border membrane vesicle phosphate uptake was not altered in sirolimus
      treated groups or by direct incubation with sirolimus. mRNA, protein abundance,
      and subcellular transporter distribution of NaPi-IIa, Pit-2 and NHE3 were not
      different between groups but NaPi-IIc mRNA expression was lower at day 7.
      Transcriptome analyses revealed candidate genes that could be involved in the
      phosphaturic response. Sirolimus caused a selective renal phosphate leakage,
      which was not mediated by NaPi-IIa or NaPi-IIc regulation or localization. We
      hypothesize that another mechanism such as a basolateral phosphate transporter
      may be responsible for the sirolimus induced phosphaturia.

PMID- 22859940
TI  - Functionalization of titanium with chitosan via silanation: evaluation of
      biological and mechanical performances.
AB  - Complications in dentistry and orthopaedic surgery are mainly induced by peri
      implant bacterial infections and current implant devices do not prevent such
      infections. The coating of antibacterial molecules such as chitosan on its
      surface would give the implant bioactive properties. The major challenge of this
      type of coating is the attachment of chitosan to a metal substrate. In this
      study, we propose to investigate the functionalization of titanium with chitosan
      via a silanation. Firstly, the surface chemistry and mechanical properties of
      such coating were evaluated. We also verified if the coated chitosan retained its
      biocompatibility with the peri-implant cells, as well as its antibacterial
      properties. FTIR and Tof-SIMS analyses confirmed the presence of chitosan on the
      titanium surface. This coating showed great scratch resistance and was strongly
      adhesive to the substrate. These mechanical properties were consistent with an
      implantology application. The Chitosan-coated surfaces showed strong inhibition
      of Actinomyces naeslundii growth; they nonetheless showed a non significant
      inhibition against Porphyromonas gingivalis after 32 hours in liquid media. The
      chitosan-coating also demonstrated good biocompatibility to NIH3T3 fibroblasts.
      Thus this method of covalent coating provides a biocompatible material with
      improved bioactive properties. These results proved that covalent coating of
      chitosan has significant potential in biomedical device implantation.

PMID- 22859941
TI  - Differences in salivary alpha-amylase and cortisol responsiveness following
      exposure to electrical stimulation versus the Trier Social Stress Tests.
AB  - BACKGROUND: Cortisol is an essential hormone in the regulation of the stress
      response along the HPA axis, and salivary cortisol has been used as a measure of
      free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also
      emerged as a novel biomarker for psychosocial stress responsiveness within the
      sympathetic adrenomedullary (SAM) system. PRINCIPAL FINDINGS: We measured sAA and
      salivary cortisol in healthy volunteers after exposure to the Trier Social Stress
      Test (TSST) and electric stimulation stress. One hundred forty-nine healthy
      volunteers participated in this study. All subjects were exposed to both the TSST
      and electric stimulation stress on separate days. We measured sAA and salivary
      cortisol levels three times immediately before, immediately after, and 20 min
      after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the
      Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests
      were administered to participants before the electrical stimulation and TSST
      protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio
      immediately after electrical stimulation and TSST exposure. Following TSST
      exposure or electrical stimulation, sAA levels displayed a rapid increase and
      recovery, returning to baseline levels 20 min after the stress challenge.
      Salivary cortisol responses showed a delayed increase, which remained
      significantly elevated from baseline levels 20 min after the stress challenge.
      Analyses revealed no differences between men and women with regard to their sAA
      response to the challenges (TSST or electric stimulations), while we found
      significantly higher salivary cortisol responses to the TSST in females. We also
      found that younger subjects tended to display higher sAA activity. Salivary
      cortisol levels were significantly correlated with the strength of the applied
      electrical stimulation. CONCLUSIONS: These preliminary results suggest that the
      HPA axis (but not the SAM system) may show differential response patterns to
      distinct kinds of stressors.

PMID- 22859943
TI  - Mixtures of conditional Gaussian scale mixtures applied to multiscale image
      representations.
AB  - We present a probabilistic model for natural images that is based on mixtures of
      Gaussian scale mixtures and a simple multiscale representation. We show that it
      is able to generate images with interesting higher-order correlations when
      trained on natural images or samples from an occlusion-based model. More
      importantly, our multiscale model allows for a principled evaluation. While it is
      easy to generate visually appealing images, we demonstrate that our model also
      yields the best performance reported to date when evaluated with respect to the
      cross-entropy rate, a measure tightly linked to the average log-likelihood. The
      ability to quantitatively evaluate our model differentiates it from other
      multiscale models, for which evaluation of these kinds of measures is usually
      intractable.

PMID- 22859942
TI  - A foldamer-dendrimer conjugate neutralizes synaptotoxic beta-amyloid oligomers.
AB  - BACKGROUND AND AIMS: Unnatural self-organizing biomimetic polymers (foldamers)
      emerged as promising materials for biomolecule recognition and inhibition. Our
      goal was to construct multivalent foldamer-dendrimer conjugates which wrap the
      synaptotoxic beta-amyloid (Abeta) oligomers with high affinity through their
      helical foldamer tentacles. Oligomeric Abeta species play pivotal role in
      Alzheimer's disease, therefore recognition and direct inhibition of this
      undruggable target is a great current challenge. METHODS AND RESULTS: Short
      helical beta-peptide foldamers with designed secondary structures and side chain
      chemistry patterns were applied as potential recognition segments and their
      binding to the target was tested with NMR methods (saturation transfer difference
      and transferred-nuclear Overhauser effect). Helices exhibiting binding in the uM
      region were coupled to a tetravalent G0-PAMAM dendrimer. In vitro biophysical
      (isothermal titration calorimetry, dynamic light scattering, transmission
      electron microscopy and size-exclusion chromatography) and biochemical tests
      (ELISA and dot blot) indicated the tight binding between the foldamer conjugates
      and the Abeta oligomers. Moreover, a selective low nM interaction with the low
      molecular weight fraction of the Abeta oligomers was found. Ex vivo
      electrophysiological experiments revealed that the new material rescues the long
      term potentiation from the toxic Abeta oligomers in mouse hippocampal slices at
      submicromolar concentration. CONCLUSIONS: The combination of the foldamer
      methodology, the fragment-based approach and the multivalent design offers a
      pathway to unnatural protein mimetics that are capable of specific molecular
      recognition, and has already resulted in an inhibitor for an extremely difficult
      target.

PMID- 22859944
TI  - A meta-analysis of interleukin-10 -592 promoter polymorphism associated with
      gastric cancer risk.
AB  - We aimed to explore the role of IL-10 -592 A/C SNP in the susceptibility to
      gastric cancer through a systematic review and meta-analysis. Each initially
      included article was scored for quality appraisal. 17 studies were eligible for
      the meta-analysis. We adopted the most probably appropriate genetic model
      (recessive model). Potential sources of heterogeneity were sought out via
      subgroup and sensitivity analyses, and publication biases were estimated. IL-10
      592 AA genotype is associated with the reduced risk of developing gastric cancer
      among Asians and even apparently observed among Asians high quality subgroup,
      suggesting IL-10-592 AA genotype may seem to be more protective from overall
      gastric cancer in Asian populations. IL-10-592 AA genotype is also associated
      with the overall reduced gastric cancer susceptibility in persons with H. pylori
      infection compared with controls without H. pylori infection, suggesting IL-10
      592 AA genotype may seem to be more protective from overall gastric cancer
      susceptibility in persons infected with H. pylori. IL-10-592 AA genotype is not
      associated with either pathologic subtypes (intestinal or diffuse) or anatomic
      subtypes (non-cardia or cardia) of gastric cancer susceptibility. Genotyping
      methods like direct sequencing should be highly advocated to be conducted in
      future well-designed high quality studies among different ethnicities or
      populations.

PMID- 22859945
TI  - Performance of health workers in the management of seriously sick children at a
      Kenyan tertiary hospital: before and after a training intervention.
AB  - BACKGROUND: Implementation of WHO case management guidelines for serious common
      childhood illnesses remains a challenge in hospitals in low-income countries. The
      impact of locally adapted clinical practice guidelines (CPGs) on the quality-of
      care of patients in tertiary hospitals has rarely been evaluated. METHODS AND
      FINDINGS: We conducted, in Kenyatta National Hospital, an uncontrolled before and
      after study with an attempt to explore intervention dose-effect relationships, as
      CPGs were disseminated and training was progressively implemented. The emergency
      triage, assessment and treatment plus admission care (ETAT+) training and locally
      adapted CPGs targeted common, serious childhood illnesses. We compared
      performance in the pre-intervention (2005) and post-intervention periods (2009)
      using quality indicators for three diseases: pneumonia, dehydration and severe
      malnutrition. The indicators spanned four domains in the continuum of care namely
      assessment, classification, treatment, and follow-up care in the initial 48 hours
      of admission. In the pre-intervention period patients' care was largely
      inconsistent with the guidelines, with nine of the 15 key indicators having
      performance of below 10%. The intervention produced a marked improvement in
      guideline adherence with an absolute effect size of over 20% observed in seven of
      the 15 key indicators; three of which had an effect size of over 50%. However,
      for all the five indicators that required sustained team effort performance
      continued to be poor, at less than 10%, in the post-intervention period. Data
      from the five-year period (2005-09) suggest some dose dependency though the
      adoption rate of the best-practices varied across diseases and over time.
      CONCLUSION: Active dissemination of locally adapted clinical guidelines for
      common serious childhood illnesses can achieve a significant impact on documented
      clinical practices, particularly for tasks that rely on competence of individual
      clinicians. However, more attention must be given to broader implementation
      strategies that also target institutional and organisational aspects of service
      delivery to further enhance quality-of-care.

PMID- 22859947
TI  - Perturbation of microRNAs in rat heart during chronic doxorubicin treatment.
AB  - Anti-cancer therapy based on anthracyclines (DNA intercalating Topoisomerase II
      inhibitors) is limited by adverse effects of these compounds on the
      cardiovascular system, ultimately causing heart failure. Despite extensive
      investigations into the effects of doxorubicin on the cardiovascular system, the
      molecular mechanisms of toxicity remain largely unknown. MicroRNAs are
      endogenously transcribed non-coding 22 nucleotide long RNAs that regulate gene
      expression by decreasing mRNA stability and translation and play key roles in
      cardiac physiology and pathologies. Increasing doses of doxorubicin, but not
      etoposide (a Topoisomerase II inhibitor devoid of cardiovascular toxicity),
      specifically induced the up-regulation of miR-208b, miR-216b, miR-215, miR-34c
      and miR-367 in rat hearts. Furthermore, the lowest dosing regime (1 mg/kg/week
      for 2 weeks) led to a detectable increase of miR-216b in the absence of
      histopathological findings or alteration of classical cardiac stress biomarkers.
      In silico microRNA target predictions suggested that a number of doxorubicin
      responsive microRNAs may regulate mRNAs involved in cardiac tissue remodeling. In
      particular miR-34c was able to mediate the DOX-induced changes of Sipa1 mRNA (a
      mitogen-induced Rap/Ran GTPase activating protein) at the post-transcriptional
      level and in a seed sequence dependent manner. Our results show that integrated
      heart tissue microRNA and mRNA profiling can provide valuable early genomic
      biomarkers of drug-induced cardiac injury as well as novel mechanistic insight
      into the underlying molecular pathways.

PMID- 22859946
TI  - Biomarkers of good EULAR response to the B cell depletion therapy in all
      seropositive rheumatoid arthritis patients: clues for the pathogenesis.
AB  - OBJECTIVE: To find out whether a high number of auto-antibodies can increase the
      probability of a "good-EULAR response" and to identify the possible biomarkers of
      response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell
      depletion therapy (BCDT). PATIENTS AND METHODS: One hundred and thirty-eight
      patients with long standing RA (LSRA), 75% non or poorly responsive to one or
      more TNFalpha blockers, all seropositive for at least one autoantibody (AAB) (RF
      IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full
      course of BCDT. The major outcomes (moderate or good-EULAR response) were
      assessed after 6 months of therapy. The IL6 and BAFF levels were also determined.
      RESULTS: At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good
      EULAR response. Having up to 5-AABs positivity increased the chances for
      treatment response. After a logistic regression analysis, however, only 4
      baseline factors arose as associated with a good-EULAR response: no steroid
      therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level
      >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the
      AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final
      predictors were no-steroid therapy and low lymphocyte count. DISCUSSION: The
      number of AABs increased the chances of being a "good-EULAR" responder. The only
      predictors, however, at the baseline of a good response in this seropositive
      cohort of RA patients were 2 simple variables--no steroids and lymphocyte count-
      and two laboratory assays--IgG-RF and BAFF.

PMID- 22859948
TI  - Insight into temperature dependence of GTPase activity in human guanylate binding
      protein-1.
AB  - Interferon-gamma induced human guanylate binding protein-1(hGBP1) belongs to a
      family of dynamin related large GTPases. Unlike all other GTPases, hGBP1
      hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37
      degrees C but GDP became significant when the hydrolysis reaction was carried out
      at 15 degrees C. The hydrolysis reaction in hGBP1 is believed to involve with a
      number of catalytic steps. To investigate the effect of temperature in the
      product formation and on the different catalytic complexes of hGBP1, we carried
      out temperature dependent GTPase assays, mutational analysis, chemical and
      thermal denaturation studies. The Arrhenius plot for both GDP and GMP
      interestingly showed nonlinear behaviour, suggesting that the product formation
      from the GTP-bound enzyme complex is associated with at least more than one step.
      The negative activation energy for GDP formation and GTPase assay with external
      GDP together indicate that GDP formation occurs through the reversible
      dissociation of GDP-bound enzyme dimer to monomer, which further reversibly
      dissociates to give the product. Denaturation studies of different catalytic
      complexes show that unlike other complexes the free energy of GDP-bound hGBP1
      decreases significantly at lower temperature. GDP formation is found to be
      dependent on the free energy of the GDP-bound enzyme complex. The decrease in the
      free energy of this complex at low temperature compared to at high is the reason
      for higher GDP formation at low temperature. Thermal denaturation studies also
      suggest that the difference in the free energy of the GTP-bound enzyme dimer
      compared to its monomer plays a crucial role in the product formation; higher
      stability favours GMP but lower favours GDP. Thus, this study provides the first
      thermodynamic insight into the effect of temperature in the product formation of
      hGBP1.

PMID- 22859949
TI  - Probing cocaine-antibody interactions in buffer and human serum.
AB  - BACKGROUND: Despite progress in cocaine immunotherapy, the kinetic and
      thermodynamic properties of antibodies which bind to cocaine and its metabolites
      are not well understood. It is also not clear how the interactions between them
      differ in a complex matrix such as the serum present in the human body. In the
      present study, we have used microscale thermophoresis (MST), isothermal titration
      calorimetry (ITC), and surface plasmon resonance (SPR) we have evaluated the
      affinity properties of a representative mouse monoclonal (mAb08) as well as those
      of polyclonal antibodies purified from vaccinated mouse and human patient serum.
      RESULTS: MST analysis of fluorescently tagged mAb08 binding to cocaine reveals an
      approximately 15 fold decrease in its equilibrium dissociation constant in 20-50%
      human serum compared with that in saline buffer. A similar trend was also found
      using enriched polyclonal antibodies purified from vaccinated mice and patient
      serum, for which we have used fluorescently tagged bovine serum albumin
      conjugated to succinyl norcocaine (BSA-SNC). This conjugate closely mimics both
      cocaine and the hapten used to raise these antibodies. The ITC data also revealed
      that cocaine has a moderate affinity of about 2 uM to 20% human serum and very
      little interaction with human serum albumin or nonspecific human IgG at that
      concentration range. In a SPR inhibition experiment, the binding of mAb08 to
      immobilized BSA-SNC was inhibited by cocaine and benzoylecgonine in a highly
      competitive manner, whereas the purified polyclonal antibodies from vaccinated
      humans and mice, revealed preferential selectivity to pharmacologically active
      cocaine but not to the inactive metabolite benzoylecgonine. We have also
      developed a simple binding model to simulate the challenges associated with
      cocaine immunotherapy using the variable quantitative and kinetic properties of
      the antibodies. CONCLUSIONS: High sensitivity calorimetric determination of
      antibody binding to cocaine and its metabolites provide valuable information for
      characterization of their interactions and thermodynamic properties. In addition
      MST measurements of antibody affinity in the presence of biological fluids will
      provide a better opportunity to make reliable decisions and facilitate the design
      of cocaine vaccines and immunization conditions. The methods should be more
      widely adopted in characterization of antibody complexes.

PMID- 22859950
TI  - Awareness and attitude towards human papillomavirus (HPV) vaccine among medical
      students in a premier medical school in India.
AB  - BACKGROUND: As preventing cancer with the help of a vaccine is a comparatively
      new concept, awareness and education about it will have important implication in
      the implementation of this strategy. MATERIALS AND METHODS: Present explorative
      questionnaire based survey included 618 MBBS students for final analysis.
      RESULTS: Majority of participants (89.6%) were well aware of the preventable
      nature of cervical cancer. Most of them (89.2%) knew that necessary factor
      responsible for cervical cancer is infection with high risk HPV. Awareness
      regarding the availability of vaccine against cervical cancer was 75.6%. Females
      had a better awareness regarding availability of vaccine, target population for
      vaccination and about the catch up program. Overall acceptance of HPV vaccine
      among the population studied was 67.8%. Medical teaching had a definitive impact
      on the understanding of this important public health issue. Females seemed to be
      more ready to accept the vaccine and recommend it to others. For our study
      population the most common source of information was medical school teaching.
      Majority of participants agreed that the most important obstacle in
      implementation of HPV vaccination program in our country is inadequate
      information and 86.2% wanted to be educated by experts in this regard.
      CONCLUSION: HPV vaccine for primary prevention of cervical cancer is a relatively
      new concept. Health professional will be able to play a pivotal role in
      popularizing this strategy.

PMID- 22859951
TI  - Adrenomedullin in ovarian cancer: foe in vitro and friend in vivo?
AB  - Stromal elements within a tumor interact with cancer cells to create a
      microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is
      an autocrine/paracrine factor produced by both stromal cells and cancer cells to
      create such a microenvironment. During differentiation of macrophages, ADM is
      produced in response to pro-inflammatory stimuli and hypoxia. In this study we
      investigated the role of ADM as a growth factor for ovarian cancer cells and as a
      modulator of macrophages. We also analyzed ADM expression levels in a
      retrospective clinical study using nanofluidic technology and assessment of ADM
      at the gene level in 220 ovarian cancer patients. To study the effects of ADM,
      ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant
      counterparts were used for proliferation assays, while monocytes from healthy
      donors were differentiated in vitro. ADM was a weak growth factor, as revealed by
      proliferation assays and cell cycle analysis. After culturing cancer cells under
      stressing conditions, such as serum starvation and/or hypoxia, ADM was found to
      be a survival factor in HEY but not in other cell lines. In macrophages, ADM
      showed activity on proliferation/differentiation, primarily in type 2 macrophages
      (M2). Unexpectedly, the clinical study revealed that high expression of ADM was
      linked to positive outcome and to cancer with low Ca125. In conclusion, although
      in vitro ADM was a potential factor in biological aggressiveness, this
      possibility was not confirmed in patients. Therefore, use of an ADM antagonist
      would be inappropriate in managing ovarian cancer patients.

PMID- 22859952
TI  - Plum (Prunus domestica) trees transformed with poplar FT1 result in altered
      architecture, dormancy requirement, and continuous flowering.
AB  - The Flowering Locus T1 (FT1) gene from Populus trichocarpa under the control of
      the 35S promoter was transformed into European plum (Prunus domestica L).
      Transgenic plants expressing higher levels of FT flowered and produced fruits in
      the greenhouse within 1 to 10 months. FT plums did not enter dormancy after cold
      or short day treatments yet field planted FT plums remained winter hardy down to
      at least -10 degrees C. The plants also displayed pleiotropic phenotypes atypical
      for plum including shrub-type growth habit and panicle flower architecture. The
      flowering and fruiting phenotype was found to be continuous in the greenhouse but
      limited to spring and fall in the field. The pattern of flowering in the field
      correlated with lower daily temperatures. This apparent temperature effect was
      subsequently confirmed in growth chamber studies. The pleitropic phenotypes
      associated with FT1 expression in plum suggests a fundamental role of this gene
      in plant growth and development. This study demonstrates the potential for a
      single transgene event to markedly affect the vegetative and reproductive growth
      and development of an economically important temperate woody perennial crop. We
      suggest that FT1 may be a useful tool to modify temperate plants to changing
      climates and/or to adapt these crops to new growing areas.

PMID- 22859953
TI  - Spatial genetic structure and mitochondrial DNA phylogeography of Argentinean
      populations of the grasshopper Dichroplus elongatus.
AB  - Many grasshopper species are considered of agronomical importance because they
      cause damage to pastures and crops. Comprehension of pest population dynamics
      requires a clear understanding of the genetic diversity and spatial structure of
      populations. In this study we report on patterns of genetic variation in the
      South American grasshopper Dichroplus elongatus which is an agricultural pest of
      crops and forage grasses of great economic significance in Argentina. We use
      Direct Amplification of Minisatellite Regions (DAMD) and partial sequences of the
      cytochrome oxydase 1 (COI) mitochondrial gene to investigate intraspecific
      structure, demographic history and gene flow patterns in twenty Argentinean
      populations of this species belonging to different geographic and biogeographic
      regions. DAMD data suggest that, although genetic drift and migration occur
      within and between populations, measurable relatedness among neighbouring
      populations declines with distance and dispersal over distances greater than 200
      km is not typical, whereas effective gene flow may occur for populations
      separated by less than 100 km. Landscape analysis was useful to detect genetic
      discontinuities associated with environmental heterogeneity reflecting the
      changing agroecosystem. The COI results indicate the existence of strong genetic
      differentiation between two groups of populations located at both margins of the
      Parana River which became separated during climate oscillations of the Middle
      Pleistocene, suggesting a significant restriction in effective dispersion
      mediated by females and large scale geographic differentiation. The number of
      migrants between populations estimated through mitochondrial and DAMD markers
      suggest that gene flow is low prompting a non-homogeneous spatial structure and
      justifying the variation through space. Moreover, the genetic analysis of both
      markers allows us to conclude that males appear to disperse more than females,
      reducing the chance of the genetic loss associated with recent anthropogenic
      fragmentation of the D. elongatus studied range.

PMID- 22859954
TI  - Comparison and analysis of membrane fouling between flocculent sludge membrane
      bioreactor and granular sludge membrane bioreactor.
AB  - The goal of this study is to investigate the effect of inoculating granules on
      reducing membrane fouling. In order to evaluate the differences in performance
      between flocculent sludge and aerobic granular sludge in membrane reactors
      (MBRs), two reactors were run in parallel and various parameters related to
      membrane fouling were measured. The results indicated that specific resistance to
      the fouling layer was five times greater than that of mixed liquor sludge in the
      granular MBR. The floc sludge more easily formed a compact layer on the membrane
      surface, and increased membrane resistance. Specifically, the floc sludge had a
      higher moisture content, extracellular polymeric substances concentration, and
      negative surface charge. In contrast, aerobic granules could improve structural
      integrity and strength, which contributed to the preferable permeate performance.
      Therefore, inoculating aerobic granules in a MBR presents an effective method of
      reducing the membrane fouling associated with floc sludge the perspective of from
      the morphological characteristics of microbial aggregates.

PMID- 22859956
TI  - GLI2 regulates TGF-beta1 in human CD4+ T cells: implications in cancer and HIV
      pathogenesis.
AB  - Elevated levels of the immunoregulatory cytokine TGF-beta1 in cancer and HIV
      infection have been linked to the suppression of protective immune responses. The
      transcriptional regulation of TGF-beta1 is complex and still not completely
      understood. We report here for the first time that the transcription factor GLI2
      regulates the expression of TGF-beta1 in human CD4(+) T cells. In silico
      screening revealed five novel putative GLI binding sites in the human TGF-beta1
      promoter. At least two of these sites within the human TGF-beta1 promoter are
      regulated by the GLI2 activator as knockdown of GLI2 in regulatory CD4(+)CD25(hi)
      T cells, high producers of TGF-beta1, significantly decreased TGF-beta1
      transcription. Additionally, naive CD4(+) T cells, low producers of TGF-beta1,
      increased their basal level of TGF-beta1 mRNA following lentiviral infection with
      GLI2. The transcriptional regulation of TGF-beta1 by GLI2 is a new extension to
      Sonic Hedgehog (SHH) and TGF-beta1 cross-regulation and may provide insight into
      the detrimental elevation of TGF-beta1 leading to pathogenesis in cancer and HIV
      infection.

PMID- 22859957
TI  - Childhood tuberculosis in household contacts of newly diagnosed TB patients.
AB  - INTRODUCTION: Childhood tuberculosis (TB), although estimated to account for a
      major proportion of the global TB disease burden, has a lower public health
      priority. Reliable research and surveillance data on childhood TB is limited in
      most regions of the world. This study was conducted to assess the burden of
      childhood TB among the household contacts of new TB patients in Karachi,
      Pakistan. METHODS: A retrospective analysis of children (<15 years) who were
      household contacts of new adult TB patients presenting to Marie Adelaide Leprosy
      Center (MALC) clinics in Karachi during the period of 2008 to 2010 was conducted.
      RESULTS: Of the household children contacts (n = 6613) screened, 317 were
      suspected and 121(1.8%) diagnosed with TB. These included 89 (73.6%) with
      pulmonary and 32 (26.4%) with extra-pulmonary disease. Smear positivity rate in
      pulmonary cases was 32.6%. Mean age of children diagnosed with TB was 11.7 (+/-
      2.8) years. Within the child-contacts screened, disease was found to be
      significantly higher among females (2.3%) in comparison to males (1.2%) (p-value
      <0.01). The commonest relationship of source cases to diagnosed children was the
      mother (n = 51, 42.1%). The source case was a female for 66.1% (n = 76) of the
      children. CONCLUSION: A smear positivity rate of 32.6% amongst pulmonary cases
      suggests their potential to spread disease and emphasizes a need to review the
      contribution of children in transmission of TB within communities. Greater
      vulnerability of the female child and considerable role of mother in disease
      transmission highlights a need to increase focus on females in TB control
      programs in Pakistan.

PMID- 22859955
TI  - High resolution crystal structure of the endo-N-Acetyl-beta-D-glucosaminidase
      responsible for the deglycosylation of Hypocrea jecorina cellulases.
AB  - Endo-N-acetyl-beta-D-glucosaminidases (ENGases) hydrolyze the glycosidic linkage
      between the two N-acetylglucosamine units that make up the chitobiose core of N
      glycans. The endo-N-acetyl-beta-D-glucosaminidases classified into glycoside
      hydrolase family 18 are small, bacterial proteins with different substrate
      specificities. Recently two eukaryotic family 18 deglycosylating enzymes have
      been identified. Here, the expression, purification and the 1.3A resolution
      structure of the ENGase (Endo T) from the mesophilic fungus Hypocrea jecorina
      (anamorph Trichoderma reesei) are reported. Although the mature protein is C
      terminally processed with removal of a 46 amino acid peptide, the protein has a
      complete (beta/alpha)8 TIM-barrel topology. In the active site, the proton donor
      (E131) and the residue stabilizing the transition state (D129) in the substrate
      assisted catalysis mechanism are found in almost identical positions as in the
      bacterial GH18 ENGases: Endo H, Endo F1, Endo F3, and Endo BT. However, the loops
      defining the substrate-binding cleft vary greatly from the previously known
      ENGase structures, and the structures also differ in some of the alpha-helices
      forming the barrel. This could reflect the variation in substrate specificity
      between the five enzymes. This is the first three-dimensional structure of a
      eukaryotic endo-N-acetyl-beta-D-glucosaminidase from glycoside hydrolase family
      18. A glycosylation analysis of the cellulases secreted by a Hypocrea jecorina
      Endo T knock-out strain shows the in vivo function of the protein. A homology
      search and phylogenetic analysis show that the two known enzymes and their
      homologues form a large but separate cluster in subgroup B of the fungal
      chitinases. Therefore the future use of a uniform nomenclature is proposed.

PMID- 22859958
TI  - Differential trypanocidal activity of novel macrolide antibiotics; correlation to
      genetic lineage.
AB  - Here we report the systematic study of the anti-trypanocidal activity of some new
      products derived from S. diastatus on 14 different T. cruzi strains spanning the
      six genetic lineages of T. cruzi. As the traditional growth inhibition curves
      giving similar IC(50) showed great differences on antibiotic and lineage tested,
      we decided to preserve the wealth of information derived from each inhibition
      curve and used an algorithm related to potency of the drugs, combined in a matrix
      data set used to generate a cluster tree. The cluster thus generated based just
      on drug susceptibility data closely resembles the phylogenies of the lineages
      derived from genetic data and provides a novel approach to correlate genetic data
      with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide
      clues on the drugs mechanism of action.

PMID- 22859960
TI  - Metabolic profiling in Maturity-onset diabetes of the young (MODY) and young
      onset type 2 diabetes fails to detect robust urinary biomarkers.
AB  - It is important to identify patients with Maturity-onset diabetes of the young
      (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic
      testing is currently expensive and many patients are therefore not assessed and
      are misclassified as having either type 1 or type 2 diabetes. Biomarkers could
      facilitate the prioritisation of patients for genetic testing. We hypothesised
      that patients with different underlying genetic aetiologies for their diabetes
      could have distinct metabolic profiles which may uncover novel biomarkers. The
      aim of this study was to perform metabolic profiling in urine from patients with
      MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte
      nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control
      subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and
      ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry
      (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14),
      GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were
      used to build a valid partial least squares discriminate analysis (PLS-DA) model
      where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No
      single metabolite contributed significantly to the separation of the patient
      groups. However, betaine, valine, glycine and glucose were elevated in the urine
      of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of
      urinary amino acids and betaine in an extended dataset did not support
      differences between patients groups. Elevated urinary glucose in HNF1A-MODY is
      consistent with the previously reported low renal threshold for glucose in this
      genetic subtype. In conclusion, we report the first metabolic profiling study in
      monogenic diabetes and show that, despite the distinct biochemical pathways
      affected, there are unlikely to be robust urinary biomarkers which distinguish
      monogenic subtypes from T2D. Our results have implications for studies
      investigating metabolic profiles in complex traits including T2D.

PMID- 22859959
TI  - Warburg effect's manifestation in aggressive pheochromocytomas and
      paragangliomas: insights from a mouse cell model applied to human tumor tissue.
AB  - A glycolytic profile unifies a group of pheochromocytomas and paragangliomas
      (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau
      (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor
      aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently
      in SDHB-patients. To date, the molecular mechanisms causing the more aggressive
      phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an
      excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has
      been developed from mouse PHEO cells (MPC). We employed this model for a
      proteomics based approach to identify changes characteristic for tumor
      aggressiveness, which we then explored in a homogeneous set of human SDHB- and
      VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2
      in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell
      model and in support of decoupling of glycolysis, the Krebs cycle and oxidative
      phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase
      levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as
      expected, decreased at complex II. Moreover, protein and mRNA expression of all
      tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors.
      Although there was no direct evidence for increased reactive oxygen species
      production, elevated superoxide dismutase 2 expression may reflect elevated
      oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that
      despite dysfunction in complex II and evidence for a glycolytic phenotype, the
      Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to
      decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2
      expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising
      therapeutic targets in other cancers. This study provides new insight into
      pathogenic mechanisms in aggressive human PHEOs/PGLs, which may lead to
      identifying new diagnostic and prognostic markers in the near future.

PMID- 22859961
TI  - Comparison of methods for competitive tests of pathway analysis.
AB  - It has been suggested that pathway analysis can complement single-SNP analysis in
      exploring genomewide association data. Pathway analysis incorporates the
      available biological knowledge of genes and SNPs and is expected to improve the
      chances of revealing the underlying genetic architecture of complex traits.
      Methods for pathway analysis can be classified as competitive (enrichment) or
      self-contained (association) according to the hypothesis tested. Although
      association tests are statistically more powerful than enrichment tests they can
      be difficult to calibrate because biases in analysis accumulate across multiple
      SNPs or genes. Furthermore, enrichment tests can be more scientifically relevant
      than association tests, as they detect pathways with relatively more evidence for
      association than the remaining genes. Here we show how some well known
      association tests can be simply adapted to test for enrichment, and compare their
      performance to some established enrichment tests. We propose versions of the
      Adaptive Rank Truncated Product (ARTP), Tail Strength Measure and Fisher's
      combination of p-values for testing the enrichment null hypothesis. We compare
      the behaviour of these proposed methods with the established Hypergeometric Test
      and Gene-Set Enrichment Analysis (GSEA). The results of the simulation study show
      that the modified version of the ARTP method has generally the best performance
      across the situations considered. The methods were also applied for finding
      enriched pathways for body mass index (BMI) and platelet function phenotypes. The
      pathway analysis of BMI identified the Vasoactive Intestinal Peptide pathway as
      significantly associated with BMI. This pathway has been previously reported as
      associated with BMI and the risk of obesity. The ARTP method was the method that
      identified the largest number of enriched pathways across all tested pathway
      databases and phenotypes. The simulation and data application results are in
      agreement with previous work on association tests and suggests that the ARTP
      should be preferred for both enrichment and association testing.

PMID- 22859962
TI  - Tuning genetic clocks employing DNA binding sites.
AB  - Periodic oscillations play a key role in cell physiology from the cell cycle to
      circadian clocks. The interplay of positive and negative feedback loops among
      genes and proteins is ubiquitous in these networks. Often, delays in a negative
      feedback loop and/or degradation rates are a crucial mechanism to obtain
      sustained oscillations. How does nature control delays and kinetic rates in
      feedback networks? Known mechanisms include proper selection of the number of
      steps composing a feedback loop and alteration of protease activity,
      respectively. Here, we show that a remarkably simple means to control both delays
      and effective kinetic rates is the employment of DNA binding sites. We illustrate
      this design principle on a widely studied activator-repressor clock motif, which
      is ubiquitous in natural systems. By suitably employing DNA target sites for the
      activator and/or the repressor, one can switch the clock "on" and "off" and
      precisely tune its period to a desired value. Our study reveals a design
      principle to engineer dynamic behavior in biomolecular networks, which may be
      largely exploited by natural systems and employed for the rational design of
      synthetic circuits.

PMID- 22859964
TI  - Perfectionism and anxiety: a paradox in intellectual giftedness?
AB  - Numerous authors reported a prevalence of perfectionism in gifted populations. In
      addition, an unhealthy form of perfectionism that leads to anxiety disorder has
      been described. Using self-report measures (CAPS and R-CMAS) with 132 children,
      we hypothesized that intellectually gifted children express a higher level of
      perfectionism and anxiety. Our results pointed out a paradox: the gifted group
      obtained a higher self-oriented perfectionism score than the control group in 6th
      grade, but present the same level of anxiety. In contrast, the gifted group
      showed the same level of perfectionism than non-gifted 5(th) graders, but
      reported a higher anxiety level. Thus, the interplay between perfectionism and
      anxiety appears to be more complex than a simple linear relationship in
      giftedness.

PMID- 22859963
TI  - Mapping genetic variants associated with beta-adrenergic responses in inbred
      mice.
AB  - beta-blockers and beta-agonists are primarily used to treat cardiovascular
      diseases. Inter-individual variability in response to both drug classes is well
      recognized, yet the identity and relative contribution of the genetic players
      involved are poorly understood. This work is the first genome-wide association
      study (GWAS) addressing the values and susceptibility of cardiovascular-related
      traits to a selective beta(1)-blocker, Atenolol (ate), and a beta-agonist,
      Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable
      traits, each measured across 22 inbred mouse strains and four pharmacological
      conditions. The genotypic panel comprised 79922 informative SNPs of the mouse
      HapMap resource. Associations were mapped by Efficient Mixed Model Association
      (EMMA), a method that corrects for the population structure and genetic
      relatedness of the various strains. A total of 205 separate genome-wide scans
      were analyzed. The most significant hits include three candidate loci related to
      cardiac and body weight, three loci for electrocardiographic (ECG) values, two
      loci for the susceptibility of atrial weight index to iso, four loci for the
      susceptibility of systolic blood pressure (SBP) to perturbations of the beta
      adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An
      additional 60 loci were suggestive for one or the other of the 27 traits, while
      46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits
      tagged unexpected regions, yet at least two loci for the susceptibility of SBP to
      beta-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid
      axis. Loci for cardiac-related traits were preferentially enriched in genes
      expressed in the heart, while 23% of the testable loci were replicated with
      datasets of the Mouse Phenome Database (MPD). Altogether these data and
      validation tests indicate that the mapped loci are relevant to the traits and
      responses studied.

PMID- 22859965
TI  - Transmission dynamics of carbapenemase-producing Klebsiella pneumoniae and
      anticipated impact of infection control strategies in a surgical unit.
AB  - BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CPKP) has been
      established as important nosocomial pathogen in many geographic regions.
      Transmission from patient to patient via the hands of healthcare workers is the
      main route of spread in the acute-care setting. METHODOLOGY/PRINCIPAL FINDINGS:
      Epidemiological and infection control data were recorded during a prospective
      observational study conducted in a surgical unit of a tertiary-care hospital in
      Greece. Surveillance culture for CPKP were obtained from all patients upon
      admission and weekly thereafter. The Ross-Macdonald model for vector-borne
      diseases was applied to obtain estimates for the basic reproduction number R(0)
      (average number of secondary cases per primary case in the absence of infection
      control) and assess the impact of infection control measures on CPKP containment
      in endemic and hyperendemic settings. Eighteen of 850 patients were colonized
      with CPKP on admission and 51 acquired CPKP during hospilazation. R(0) reached 2
      and exceeded unity for long periods of time under the observed hand hygiene
      compliance (21%). The minimum hand hygiene compliance level necessary to control
      transmission was 50%. Reduction of 60% to 90% in colonized patients on admission,
      through active surveillance culture, contact precautions and isolation/cohorting,
      in combination with 60% compliance in hand hygiene would result in rapid decline
      in CPKP prevalence within 8-12 weeks. Antibiotics restrictions did not have a
      substantial benefit when an aggressive control strategy was implemented.
      CONCLUSIONS/SIGNIFICANCE: Surveillance culture on admission and
      isolation/cohorting of colonized patients coupled with moderate hand hygiene
      compliance and contact precautions may lead to rapid control of CPKP in endemic
      and hyperendemic healthcare settings.

PMID- 22859966
TI  - Stimulation of Wnt/beta-catenin pathway in human CD8+ T lymphocytes from blood
      and lung tumors leads to a shared young/memory phenotype.
AB  - Cancer can be treated by adoptive cell transfer (ACT) of T lymphocytes. However,
      how to optimally raise human T cells to a differentiation state allowing the best
      persistence in ACT is a challenge. It is possible to differentiate mouse CD8(+) T
      cells towards stem cell-like memory (T(SCM)) phenotype upon TCR stimulation with
      Wnt/beta-catenin pathway activation. Here, we evaluated if T(SCM) can be obtained
      from human mature CD8(+) T cells following TCR and Wnt/beta-catenin activation
      through treatment with the chemical agent 4,6-disubstituted pyrrolopyrimidine
      (TWS119), which inhibits the glycogen synthase kinase-3beta (GSK-3beta), key
      inhibitor of the Wnt pathway. Human CD8(+) T cells isolated from peripheral blood
      or tumor-infiltrating lymphocytes (TIL), and treated with TWS119 gave rise to
      CD62L(+)CD45RA(+) cells, indicative of early differentiated stage, also
      expressing CD127 which is normally found on memory cells, and CD133, an
      hematopoietic stem cell marker. T(SCM) cells raised from either TIL or blood
      secreted numerous inflammatory mediators, but in lower amounts than those
      measured without TWS119. Finally, generated T(SCM) CD8(+) T cells expressed
      elevated Bcl-2 and no detectable caspase-3 activity, suggesting increased
      persistence. Our data support a role for Wnt/beta-catenin pathway in promoting
      the T(SCM) subset in human CD8(+) T cells from TIL and the periphery, which are
      relevant for ACT.

PMID- 22859967
TI  - Rapid changes in cardiac myofilament function following the acute activation of
      estrogen receptor-alpha.
AB  - Estrogens have well-recognized and complex cardiovascular effects, including
      altering myocardial contractility through changes in myofilament function. The
      presence of multiple estrogen receptor (ER) isoforms in the heart may explain
      some discrepant findings about the cardiac effects of estrogens. Most studies
      examining the impact of estrogens on the heart have focused on chronic changes in
      estrogen levels, and have not investigated rapid, non-genomic pathways. The first
      objective of this study was to determine how acute activation of ERalpha impacts
      cardiac myofilaments. Nongenomic myocardial estrogen signaling is associated with
      the activation of a variety of signaling pathways. p38 MAPK has been implicated
      in acute ER signaling in the heart, and is known to affect myofilament function.
      Thus, the second objective of this study was to determine if acute ERalpha
      activation mediates its myofilament effects through p38 MAPK recruitment. Hearts
      from female C57Bl/6 mice were perfused with the ERalpha agonist PPT and
      myofilaments isolated. Activation of ERalpha depressed actomyosin MgATPase
      activity and decreased myofilament calcium sensitivity. Inhibition of p38 MAPK
      attenuated the myofilament effects of ERalpha activation. ERalpha stimulation did
      not affect global myofilament protein phosphorylation, but troponin I
      phosphorylation at the putative PKA phosphorylation sites was decreased. Changes
      in myofilament activation did not translate into alterations in whole heart
      function. The present study provides evidence supporting rapid, non-genomic
      changes in cardiac myofilament function following acute ERalpha stimulation
      mediated by the p38 MAPK pathway.

PMID- 22859969
TI  - Experimental evidence for the effect of small wind turbine proximity and
      operation on bird and bat activity.
AB  - The development of renewable energy technologies such as wind turbines forms a
      vital part of strategies to reduce greenhouse gas emissions worldwide. Although
      large wind farms generate the majority of wind energy, the small wind turbine
      (SWT, units generating <50 kW) sector is growing rapidly. In spite of evidence of
      effects of large wind farms on birds and bats, effects of SWTs on wildlife have
      not been studied and are likely to be different due to their potential siting in
      a wider range of habitats. We present the first study to quantify the effects of
      SWTs on birds and bats. Using a field experiment, we show that bird activity is
      similar in two distance bands surrounding a sample of SWTs (between 6-18 m hub
      height) and is not affected by SWT operation at the fine scale studied. At
      shorter distances from operating turbines (0-5 m), bat activity (measured as the
      probability of a bat "pass" per hour) decreases from 84% (71-91%) to 28% (11-54%)
      as wind speed increases from 0 to 14 m/s. This effect is weaker at greater
      distances (20-25 m) from operating turbines (activity decreases from 80% (65-89%)
      to 59% (32-81%)), and absent when they are braked. We conclude that bats avoid
      operating SWTs but that this effect diminishes within 20 m. Such displacement
      effects may have important consequences especially in landscapes where suitable
      habitat is limiting. Planning guidance for SWTs is currently lacking. Based on
      our results we recommend that they are sited at least 20 m away from potentially
      valuable bat habitat.

PMID- 22859970
TI  - Multi-locus variable number of tandem repeat analysis for rapid and accurate
      typing of virulent multidrug resistant Escherichia coli clones.
AB  - One hundred E. coli isolates from Norway (n = 37), Sweden (n = 24), UK (n = 20)
      and Spain (n = 19), producing CTX-M-type - (n = 84), or SHV-12 (n = 4) extended
      spectrum beta-lactamases, or the plasmid mediated AmpC, CMY-2 (n = 12), were
      typed using multi-locus sequence typing (MLST) and multi-locus variable number of
      tandem repeat analysis (MLVA). Isolates clustered into 33 Sequence Types (STs)
      and 14 Sequence Type Complexes (STCs), and 58 MLVA-Types (MTs) and 25 different
      MLVA-Type Complexes (MTCs). A strong agreement between the MLST profile and MLVA
      typing results was observed, in which all ST131-isolates (n = 39) and most of the
      STC-648 (n = 10), STC-38 (n = 9), STC-10 (n = 9), STC-405 (n = 8) and STC-23 (n =
      6) isolates were clustered distinctly into MTC-29, -36, -20, -14, -10 and -39,
      respectively. MLVA is a rapid and accurate tool for genotyping isolates of
      globally disseminated virulent multidrug resistant E. coli lineages, including
      ST131.

PMID- 22859968
TI  - The natural history of class I primate alcohol dehydrogenases includes gene
      duplication, gene loss, and gene conversion.
AB  - BACKGROUND: Gene duplication is a source of molecular innovation throughout
      evolution. However, even with massive amounts of genome sequence data,
      correlating gene duplication with speciation and other events in natural history
      can be difficult. This is especially true in its most interesting cases, where
      rapid and multiple duplications are likely to reflect adaptation to rapidly
      changing environments and life styles. This may be so for Class I of alcohol
      dehydrogenases (ADH1s), where multiple duplications occurred in primate lineages
      in Old and New World monkeys (OWMs and NWMs) and hominoids. METHODOLOGY/PRINCIPAL
      FINDINGS: To build a preferred model for the natural history of ADH1s, we
      determined the sequences of nine new ADH1 genes, finding for the first time
      multiple paralogs in various prosimians (lemurs, strepsirhines). Database mining
      then identified novel ADH1 paralogs in both macaque (an OWM) and marmoset (a
      NWM). These were used with the previously identified human paralogs to resolve
      controversies relating to dates of duplication and gene conversion in the ADH1
      family. Central to these controversies are differences in the topologies of trees
      generated from exonic (coding) sequences and intronic sequences.
      CONCLUSIONS/SIGNIFICANCE: We provide evidence that gene conversions are the
      primary source of difference, using molecular clock dating of duplications and
      analyses of microinsertions and deletions (micro-indels). The tree topology
      inferred from intron sequences appear to more correctly represent the natural
      history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs) and catarrhines
      (OWMs and hominoids) having arisen by duplications shortly predating the
      divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose
      independently. Finally, we identify errors in database interpretation as the
      source of controversies concerning gene conversion. These analyses provide a
      model for the natural history of ADH1s that posits four ADH1 paralogs in the
      ancestor of Catarrhine and Platyrrhine primates, followed by the loss of an ADH1
      paralog in the human lineage.

PMID- 22859971
TI  - Effect of plasma membrane cholesterol depletion on glucose transport regulation
      in leukemia cells.
AB  - GLUT1 is the predominant glucose transporter in leukemia cells, and the
      modulation of glucose transport activity by cytokines, oncogenes or metabolic
      stresses is essential for their survival and proliferation. However, the
      molecular mechanisms allowing to control GLUT1 trafficking and degradation are
      still under debate. In this study we investigated whether plasma membrane
      cholesterol depletion plays a role in glucose transport activity in M07e cells, a
      human megakaryocytic leukemia line. To this purpose, the effect of cholesterol
      depletion by methyl-beta-cyclodextrin (MBCD) on both GLUT1 activity and
      trafficking was compared to that of the cytokine Stem Cell Factor (SCF). Results
      show that, like SCF, MBCD led to an increased glucose transport rate and caused a
      subcellular redistribution of GLUT1, recruiting intracellular transporter
      molecules to the plasma membrane. Due to the role of caveolae/lipid rafts in
      GLUT1 stimulation in response to many stimuli, we have also investigated the
      GLUT1 distribution along the fractions obtained after non ionic detergent
      treatment and density gradient centrifugation, which was only slightly changed
      upon MBCD treatment. The data suggest that MBCD exerts its action via a
      cholesterol-dependent mechanism that ultimately results in augmented GLUT1
      translocation. Moreover, cholesterol depletion triggers GLUT1 translocation
      without the involvement of c-kit signalling pathway, in fact MBCD effect does not
      involve Akt and PLCgamma phosphorylation. These data, together with the
      observation that the combined MBCD/SCF cell treatment caused an additive effect
      on glucose uptake, suggest that the action of SCF and MBCD may proceed through
      two distinct mechanisms, the former following a signalling pathway, and the
      latter possibly involving a novel cholesterol dependent mechanism.

PMID- 22859972
TI  - The disappearing seasonality of autism conceptions in California.
AB  - BACKGROUND: Autism incidence and prevalence have increased dramatically in the
      last two decades. The autism caseload in California increased 600% between 1992
      and 2006, yet there is little consensus as to the cause. Studying the seasonality
      of conceptions of children later diagnosed with autism may yield clues to
      potential etiological drivers. OBJECTIVE: To assess if the conceptions of
      children later diagnosed with autism cluster temporally in a systematic manner
      and whether any pattern of temporal clustering persists over time. METHOD: We
      searched for seasonality in conceptions of children later diagnosed with autism
      by applying a one-dimensional scan statistic with adaptive temporal windows on
      case and control population data from California for 1992 through 2000. We tested
      for potential confounding effects from known risk factors using logistic
      regression models. RESULTS: There is a consistent but decreasing seasonal pattern
      in the risk of conceiving a child later diagnosed with autism in November for the
      first half of the study period. Temporal clustering of autism conceptions is not
      an artifact of composition with respect to known risk factors for autism such as
      socio-economic status. CONCLUSION: There is some evidence of seasonality in the
      risk of conceiving a child later diagnosed with autism. Searches for
      environmental factors related to autism should allow for the possibility of risk
      factors or etiological drivers that are seasonally patterned and that appear and
      remain salient for a discrete number of years.

PMID- 22859973
TI  - Internal lattice reconfiguration for diversity tuning in Cellular Genetic
      Algorithms.
AB  - Cellular Genetic Algorithms (cGAs) have attracted the attention of researchers
      due to their high performance, ease of implementation and massive parallelism.
      Maintaining an adequate balance between exploitative and explorative search is
      essential when studying evolutionary optimization techniques. In this respect,
      cGAs inherently possess a number of structural configuration parameters that are
      able to sustain diversity during evolution. In this study, the internal
      reconfiguration of the lattice is proposed to constantly or adaptively control
      the exploration-exploitation trade-off. Genetic operators are characterized in
      their simplest form since algorithmic performance is assessed on implemented
      reconfiguration mechanisms. Moreover, internal reconfiguration allows the
      adjacency of individuals to be maintained. Hence, any improvement in performance
      is only a consequence of topological changes. Two local selection methods
      presenting opposite selection pressures are used in order to evaluate the
      influence of the proposed techniques. Problems ranging from continuous to real
      world and combinatorial are tackled. Empirical results are supported
      statistically in terms of efficiency and efficacy.

PMID- 22859974
TI  - Sequencing intractable DNA to close microbial genomes.
AB  - Advancement in high throughput DNA sequencing technologies has supported a rapid
      proliferation of microbial genome sequencing projects, providing the genetic
      blueprint for in-depth studies. Oftentimes, difficult to sequence regions in
      microbial genomes are ruled "intractable" resulting in a growing number of
      genomes with sequence gaps deposited in databases. A procedure was developed to
      sequence such problematic regions in the "non-contiguous finished" Desulfovibrio
      desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus
      genome (1 intractable gap). The polynucleotides surrounding each gap formed GC
      rich secondary structures making the regions refractory to amplification and
      sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped
      PCR extension cycle supported amplification and closure of all gap regions in
      both genomes. The developed procedures support accurate gene annotation, and
      provide a step-wise method that reduces the effort required for genome finishing.

PMID- 22859975
TI  - Gamma activation in young people with autism spectrum disorders and typically
      developing controls when viewing emotions on faces.
AB  - BACKGROUND: Behavioural studies have highlighted irregularities in recognition of
      facial affect in children and young people with autism spectrum disorders (ASDs).
      Recent findings from studies utilising electroencephalography (EEG) and
      magnetoencephalography (MEG) have identified abnormal activation and irregular
      maintenance of gamma (>30 Hz) range oscillations when ASD individuals attempt
      basic visual and auditory tasks. METHODOLOGY/PRINCIPAL FINDINGS: The pilot study
      reported here is the first study to use spatial filtering techniques in MEG to
      explore face processing in children with ASD. We set out to examine theoretical
      suggestions that gamma activation underlying face processing may be different in
      a group of children and young people with ASD (n = 13) compared to typically
      developing (TD) age, gender and IQ matched controls. Beamforming and virtual
      electrode techniques were used to assess spatially localised induced and evoked
      activity. While lower-band (3-30 Hz) responses to faces were similar between
      groups, the ASD gamma response in occipital areas was observed to be largely
      absent when viewing emotions on faces. Virtual electrode analysis indicated the
      presence of intact evoked responses but abnormal induced activity in ASD
      participants. CONCLUSIONS/SIGNIFICANCE: These findings lend weight to previous
      suggestions that specific components of the early visual response to emotional
      faces is abnormal in ASD. Elucidation of the nature and specificity of these
      findings is worthy of further research.

PMID- 22859976
TI  - Characterization of immune responses induced by immunization with the HA DNA
      vaccines of two antigenically distinctive H5N1 HPAIV isolates.
AB  - The evolution of the H5N1 highly pathogenic avian influenza virus (HPAIV) has
      resulted in high sequence variations and diverse antigenic properties in
      circulating viral isolates. We investigated immune responses induced by HA DNA
      vaccines of two contemporary H5N1 HPAIV isolates, A/bar-headed
      goose/Qinghai/3/2005 (QH) and A/chicken/Shanxi/2/2006 (SX) respectively, against
      the homologous as well as the heterologous virus isolate for comparison.
      Characterization of antibody responses induced by immunization with QH-HA and SX
      HA DNA vaccines showed that the two isolates are antigenically distinctive.
      Interestingly, after immunization with the QH-HA DNA vaccine, subsequent boosting
      with the SX-HA DNA vaccine significantly augmented antibody responses against the
      QH isolate but only induced low levels of antibody responses against the SX
      isolate. Conversely, after immunization with the SX-HA DNA vaccine, subsequent
      boosting with the QH-HA DNA vaccine significantly augmented antibody responses
      against the SX isolate but only induced low levels of antibody responses against
      the QH isolate. In contrast to the antibody responses, cross-reactive T cell
      responses are readily detected between these two isolates at similar levels.
      These results indicate the existence of original antigenic sin (OAS) between
      concurrently circulating H5N1 HPAIV strains, which may need to be taken into
      consideration in vaccine development against the potential H5N1 HPAIV pandemic.

PMID- 22859977
TI  - Synthetic spike-in standards improve run-specific systematic error analysis for
      DNA and RNA sequencing.
AB  - While the importance of random sequencing errors decreases at higher DNA or RNA
      sequencing depths, systematic sequencing errors (SSEs) dominate at high
      sequencing depths and can be difficult to distinguish from biological variants.
      These SSEs can cause base quality scores to underestimate the probability of
      error at certain genomic positions, resulting in false positive variant calls,
      particularly in mixtures such as samples with RNA editing, tumors, circulating
      tumor cells, bacteria, mitochondrial heteroplasmy, or pooled DNA. Most algorithms
      proposed for correction of SSEs require a data set used to calculate association
      of SSEs with various features in the reads and sequence context. This data set is
      typically either from a part of the data set being "recalibrated" (Genome
      Analysis ToolKit, or GATK) or from a separate data set with special
      characteristics (SysCall). Here, we combine the advantages of these approaches by
      adding synthetic RNA spike-in standards to human RNA, and use GATK to recalibrate
      base quality scores with reads mapped to the spike-in standards. Compared to
      conventional GATK recalibration that uses reads mapped to the genome, spike-ins
      improve the accuracy of Illumina base quality scores by a mean of 5 Phred-scaled
      quality score units, and by as much as 13 units at CpG sites. In addition, since
      the spike-in data used for recalibration are independent of the genome being
      sequenced, our method allows run-specific recalibration even for the many species
      without a comprehensive and accurate SNP database. We also use GATK with the
      spike-in standards to demonstrate that the Illumina RNA sequencing runs
      overestimate quality scores for AC, CC, GC, GG, and TC dinucleotides, while SOLiD
      has less dinucleotide SSEs but more SSEs for certain cycles. We conclude that
      using these DNA and RNA spike-in standards with GATK improves base quality score
      recalibration.

PMID- 22859978
TI  - Population processes at multiple spatial scales maintain diversity and adaptation
      in the Linum marginale--Melampsora lini association.
AB  - Host-pathogen coevolution is a major driver of species diversity, with an
      essential role in the generation and maintenance of genetic variation in host
      resistance and pathogen infectivity. Little is known about how resistance and
      infectivity are structured across multiple geographic scales and what eco
      evolutionary processes drive these patterns. Across southern Australia, the wild
      flax Linum marginale is frequently attacked by its rust fungus Melampsora lini.
      Here, we compare the genetic and phenotypic structure of resistance and
      infectivity among population pairs from two regions where environmental
      differences associate with specific life histories and mating systems. We find
      that both host and pathogen populations are genetically distinct between these
      regions. The region with outcrossing hosts and pathogens that go through asexual
      cycles followed by sexual reproduction showed greater diversity of resistance and
      infectivity phenotypes, higher levels of resistance and less clumped within
      population spatial distribution of resistance. However, in the region where
      asexual pathogens infect selfing hosts, pathogens were more infective and better
      adapted to sympatric hosts. Our findings largely agree with expectations based on
      the distinctly different host mating systems in the two regions, with a likely
      advantage for hosts undergoing recombination. For the pathogen in this system,
      sexual reproduction may primarily be a survival mechanism in the region where it
      is observed. While it appears to potentially have adverse effects on local
      adaptation in the short term, it may be necessary for longer-term coevolution
      with outcrossing hosts.

PMID- 22859979
TI  - Palaeoenvironmental shifts drove the adaptive radiation of a noctuid stemborer
      tribe (Lepidoptera, Noctuidae, Apameini) in the miocene.
AB  - Between the late Oligocene and the early Miocene, climatic changes have shattered
      the faunal and floral communities and drove the apparition of new ecological
      niches. Grassland biomes began to supplant forestlands, thus favouring a large
      scale ecosystem turnover. The independent adaptive radiations of several mammal
      lineages through the evolution of key innovations are classic examples of these
      changes. However, little is known concerning the evolutionary history of other
      herbivorous groups in relation with this modified environment. It is especially
      the case in phytophagous insect communities, which have been rarely studied in
      this context despite their ecological importance. Here, we investigate the
      phylogenetic and evolutionary patterns of grass-specialist moths from the species
      rich tribe Apameini (Lepidoptera, Noctuidae). The molecular dating analyses
      carried out over the corresponding phylogenetic framework reveal an origin around
      29 million years ago for the Apameini. Ancestral state reconstructions indicate
      (i) a potential Palaearctic origin of the tribe Apameini associated with a major
      dispersal event in Afrotropics for the subtribe Sesamiina; (ii) a recent
      colonization from Palaearctic of the New World and Oriental regions by several
      independent lineages; and (iii) an ancestral association of the tribe Apameini
      over grasses (Poaceae). Diversification analyses indicate that diversification
      rates have not remained constant during the evolution of the group, as underlined
      by a significant shift in diversification rates during the early Miocene.
      Interestingly, this age estimate is congruent with the development of grasslands
      at this time. Rather than clade ages, variations in diversification rates among
      genera better explain the current differences in species diversity. Our results
      underpin a potential adaptive radiation of these phytophagous moths with the
      family Poaceae in relation with the major environmental shifts that have occurred
      in the Miocene.

PMID- 22859980
TI  - Monitoring butterfly abundance: beyond Pollard walks.
AB  - Most butterfly monitoring protocols rely on counts along transects (Pollard
      walks) to generate species abundance indices and track population trends. It is
      still too often ignored that a population count results from two processes: the
      biological process (true abundance) and the statistical process (our ability to
      properly quantify abundance). Because individual detectability tends to vary in
      space (e.g., among sites) and time (e.g., among years), it remains unclear
      whether index counts truly reflect population sizes and trends. This study
      compares capture-mark-recapture (absolute abundance) and count-index (relative
      abundance) monitoring methods in three species (Maculinea nausithous and Iolana
      iolas: Lycaenidae; Minois dryas: Satyridae) in contrasted habitat types. We
      demonstrate that intraspecific variability in individual detectability under
      standard monitoring conditions is probably the rule rather than the exception,
      which questions the reliability of count-based indices to estimate and compare
      specific population abundance. Our results suggest that the accuracy of count
      based methods depends heavily on the ecology and behavior of the target species,
      as well as on the type of habitat in which surveys take place. Monitoring
      programs designed to assess the abundance and trends in butterfly populations
      should incorporate a measure of detectability. We discuss the relative advantages
      and inconveniences of current monitoring methods and analytical approaches with
      respect to the characteristics of the species under scrutiny and resources
      availability.

PMID- 22859981
TI  - A novel association between two trypanosome-specific factors and the conserved L5
      5S rRNA complex.
AB  - P34 and P37 are two previously identified RNA binding proteins in the flagellate
      protozoan Trypanosoma brucei. RNA interference studies have determined that the
      proteins are involved in and essential for ribosome biogenesis. The proteins
      interact with the 5S rRNA with nearly identical binding characteristics. We have
      shown that this interaction is achieved mainly through the LoopA region of the
      RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now
      provide evidence to show that these factors form a novel pre-ribosomal particle
      through interactions with both 5S rRNA and the L5 ribosomal protein. Further in
      silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S
      rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that
      P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it
      and aiding in the early steps of ribosome biogenesis.

PMID- 22859982
TI  - Amusia results in abnormal brain activity following inappropriate intonation
      during speech comprehension.
AB  - Pitch processing is a critical ability on which humans' tonal musical experience
      depends, and which is also of paramount importance for decoding prosody in
      speech. Congenital amusia refers to deficits in the ability to properly process
      musical pitch, and recent evidence has suggested that this musical pitch disorder
      may impact upon the processing of speech sounds. Here we present the first
      electrophysiological evidence demonstrating that individuals with amusia who
      speak Mandarin Chinese are impaired in classifying prosody as appropriate or
      inappropriate during a speech comprehension task. When presented with
      inappropriate prosody stimuli, control participants elicited a larger P600 and
      smaller N100 relative to the appropriate condition. In contrast, amusics did not
      show significant differences between the appropriate and inappropriate conditions
      in either the N100 or the P600 component. This provides further evidence that the
      pitch perception deficits associated with amusia may also affect intonation
      processing during speech comprehension in those who speak a tonal language such
      as Mandarin, and suggests music and language share some cognitive and neural
      resources.

PMID- 22859983
TI  - Constitutive phosphorylation of interferon receptor A-associated signaling
      proteins in systemic lupus erythematosus.
AB  - BACKGROUND: Overexpression of type I interferon (IFN-I)-induced genes is a common
      feature of systemic lupus erythematosus (SLE) and its experimental models, but
      the participation of endogenous overproduction of IFN-I on it is not clear. To
      explore the possibility that abnormally increased IFN-I receptor (IFNAR)
      signaling could participate in IFN-I-induced gene overexpression of SLE, we
      examined the phosphorylation status of the IFNAR-associated signaling partners
      Jak1 and STAT2, and its relation with expression of its physiologic inhibitor
      SOCS1 and with plasma levels of IFNalpha and IFN-like activity.
      METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells (PBMC) from
      SLE patients with or without disease activity and healthy controls cultured in
      the presence or in the absence of IFNbeta were examined by immunoprecipitation
      and/or western blotting for expression of the two IFNAR chains, Jak1, Tyk2, and
      STAT2 and their phosphorylated forms. In SLE but not in healthy control PBMC,
      Jak1 and STAT2 were constitutively phosphorylated, even in the absence of disease
      activity (basal pJak1: controls vs. active SLE p<0.0001 and controls vs. inactive
      SLE p = 0.0006; basal pSTAT2: controls vs. active and inactive SLE p<0.0001).
      Although SOCS1 protein was slightly but significantly decreased in SLE in the
      absence or in the presence of IFNbeta (p = 0.0096 to p<0.0001), in SOCS1 mRNA
      levels were markedly decreased (p = 0.036 to p<0.0001). IFNbeta induced higher
      levels of the IFN-I-dependent MxA protein mRNA in SLE than in healthy controls,
      whereas the opposite was observed for SOCS1. Although there was no relation to
      increased serum IFNalpha, active SLE plasma could induce expression of IFN
      dependent genes by normal PBMC. CONCLUSIONS/SIGNIFICANCE: These findings suggest
      that in some SLE patients IFN-I dependent gene expression could be the result of
      a low IFNAR signaling threshold.

PMID- 22859985
TI  - Effectiveness of seasonal influenza vaccines against influenza-associated
      illnesses among US military personnel in 2010-11: a case-control approach.
AB  - INTRODUCTION: Following the 2009 influenza A/H1N1 (pH1N1) pandemic, both seasonal
      and pH1N1 viruses circulated in the US during the 2010-2011 influenza season;
      influenza vaccine effectiveness (VE) may vary between live attenuated (LAIV) and
      trivalent inactivated (TIV) vaccines as well as by virus subtype. MATERIALS AND
      METHODS: Vaccine type and virus subtype-specific VE were determined for US
      military active component personnel for the period of September 1, 2010 through
      April 30, 2011. Laboratory-confirmed influenza-related medical encounters were
      compared to matched individuals with a non-respiratory illness (healthy
      controls), and unmatched individuals who experienced a non-influenza respiratory
      illness (test-negative controls). Odds ratios (OR) and VE estimates were
      calculated overall, by vaccine type and influenza subtype. RESULTS: A total of
      603 influenza cases were identified. Overall VE was relatively low and similar
      regardless of whether healthy controls (VE = 26%, 95% CI: -1 to 45) or test
      negative controls (VE = 29%, 95% CI: -6 to 53) were used as comparison groups.
      Using test-negative controls, vaccine type-specific VE was found to be higher for
      TIV (53%, 95% CI: 25 to 71) than for LAIV (VE = -13%, 95% CI: -77 to 27).
      Influenza subtype-specific analyses revealed moderate protection against A/H3 (VE
      = 58%, 95% CI: 21 to 78), but not against A/H1 (VE = -38%, 95% CI: -211 to 39) or
      B (VE = 34%, 95% CI: -122 to 80). CONCLUSION: Overall, a low level of protection
      against clinically-apparent, laboratory-confirmed, influenza was found for the
      2010-11 seasonal influenza vaccines. TIV immunization was associated with higher
      protection than LAIV, however, no protection against A/H1 was noted, despite
      inclusion of a pandemic influenza strain as a vaccine component for two
      consecutive years. Vaccine virus mismatch or lower immunogenicity may have
      contributed to these findings and deserve further examination in controlled
      studies. Continued assessment of VE in military personnel is essential in order
      to better inform vaccination policy decisions.

PMID- 22859984
TI  - Selfish little circles: transmission bias and evolution of large deletion-bearing
      mitochondrial DNA in Caenorhabditis briggsae nematodes.
AB  - Selfish DNA poses a significant challenge to genome stability and organismal
      fitness in diverse eukaryotic lineages. Although selfish mitochondrial DNA
      (mtDNA) has known associations with cytoplasmic male sterility in numerous
      gynodioecious plant species and is manifested as petite mutants in experimental
      yeast lab populations, examples of selfish mtDNA in animals are less common. We
      analyzed the inheritance and evolution of mitochondrial DNA bearing large
      heteroplasmic deletions including nad5 gene sequences (nad5Delta mtDNA), in the
      nematode Caenorhabditis briggsae. The deletion is widespread in C. briggsae
      natural populations and is associated with deleterious organismal effects. We
      studied the inheritance patterns of nad5Delta mtDNA using eight sets of C.
      briggsae mutation-accumulation (MA) lines, each initiated from a different
      natural strain progenitor and bottlenecked as single hermaphrodites across
      generations. We observed a consistent and strong drive toward higher levels of
      deletion-bearing molecules in the heteroplasmic pool of mtDNA after ten
      generations of bottlenecking. Our results demonstrate a uniform transmission bias
      whereby nad5Delta mtDNA accumulates to higher levels relative to intact mtDNA in
      multiple genetically diverse natural strains of C. briggsae. We calculated an
      average 1% per-generation transmission bias for deletion-bearing mtDNA relative
      to intact genomes. Our study, coupled with known deleterious phenotypes
      associated with high deletion levels, shows that nad5Delta mtDNA are selfish
      genetic elements that have evolved in natural populations of C. briggsae,
      offering a powerful new system to study selfish mtDNA dynamics in metazoans.

PMID- 22859986
TI  - Downregulation of miR-205 modulates cell susceptibility to oxidative and
      endoplasmic reticulum stresses in renal tubular cells.
AB  - BACKGROUND: Oxidative stress and endoplasmic reticulum (ER) stress play a crucial
      role in tubular damage in both acute kidney injury (AKI) and chronic kidney
      disease (CKD). While the pathophysiological contribution of microRNAs (miRNA) to
      renal damage has also been highlighted, the effect of miRNA on renal damage under
      oxidative and ER stresses conditions remains elusive. METHODS: We assessed
      changes in miRNA expression in the cultured renal tubular cell line HK-2 under
      hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA
      microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was
      evaluated by cell survival rate, intracellular reactive oxygen species (ROS)
      level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA
      overexpressed HK-2 under these stress conditions. The target gene of miRNA was
      identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs
      whose expression was significantly altered by oxidative and ER stresses,
      respectively. Among these, expression of miR-205 was markedly decreased in both
      stress conditions. Functional analysis revealed that decreased miR-205 led to an
      increase in cell susceptibility to oxidative and ER stresses, and that this
      increase was associated with the induction of intracellular ROS and suppression
      of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell
      growth or morphology, cell viability under oxidative or ER stress conditions was
      partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl
      hydroxylase 1 (PHD1/EGLN2) gene and suppressed the transcription level of EGLN2,
      which modulates both intracellular ROS level and ER stress state. CONCLUSIONS:
      miR-205 serves a protective role against both oxidative and ER stresses via the
      suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may
      represent a novel therapeutic target in AKI and CKD associated with oxidative or
      ER stress in tubules.

PMID- 22859987
TI  - Diagnostic biopsy does not commonly induce intratumoral CD8 T cell infiltration
      in Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma is a polyomavirus-associated cancer that is
      strongly linked with T lymphocyte immune suppression in epidemiologic studies.
      CD8+ T cell infiltration into MCC tumors (intratumoral) has recently been shown
      to be strongly predictive of improved survival. In contrast, the presence of CD8+
      T cells at the border of the tumor (peritumoral) had no independent prognostic
      value. Spontaneous regression has been reported for MCC approximately one
      thousand times more often than would be expected given the frequency of this
      cancer. Many of these events began shortly after biopsy, and in some cases
      lymphocytic infiltration was described. METHODOLOGY/PRINCIPAL FINDINGS: To
      determine whether CD8+ lymphocyte infiltration in MCC tumors is commonly altered
      by biopsy.33 MCC patients who had microscopic confirmation of MCC on both an
      initial biopsy and a re-excision specimen were included in this study.
      Intratumoral and peritumoral CD8 lymphocyte infiltration was quantitated using
      immunohistochemistry and compared using the paired t-test in biopsy versus re
      excision samples. There was a trend toward increased CD8 infiltration after
      biopsy in a peritumoral ('stalled') pattern (p = 0.08), however, biopsy was not
      associated with a significant increase in CD8 T cells in the clinically more
      important intratumoral location (p = 0.58). CONCLUSIONS/SIGNIFICANCE: The initial
      diagnostic biopsy for MCC does not commonly alter intratumoral CD8+ T cell
      infiltration, suggesting it does not directly induce immunologic recognition of
      this cancer. Because CD8 infiltration is typically stable after biopsy, this
      parameter may be useful to assess the efficacy of future immune therapies for
      this virus-associated, immunogenic, often-lethal cancer.

PMID- 22859988
TI  - An expanded multilocus sequence typing scheme for propionibacterium acnes:
      investigation of 'pathogenic', 'commensal' and antibiotic resistant strains.
AB  - The Gram-positive bacterium Propionibacterium acnes is a member of the normal
      human skin microbiota and is associated with various infections and clinical
      conditions. There is tentative evidence to suggest that certain lineages may be
      associated with disease and others with health. We recently described a
      multilocus sequence typing scheme (MLST) for P. acnes based on seven housekeeping
      genes (http://pubmlst.org/pacnes). We now describe an expanded eight gene version
      based on six housekeeping genes and two 'putative virulence' genes (eMLST) that
      provides improved high resolution typing (91eSTs from 285 isolates), and
      generates phylogenies congruent with those based on whole genome analysis. When
      compared with the nine gene MLST scheme developed at the University of Bath, UK,
      and utilised by researchers at Aarhus University, Denmark, the eMLST method
      offers greater resolution. Using the scheme, we examined 208 isolates from
      disparate clinical sources, and 77 isolates from healthy skin. Acne was
      predominately associated with type IA(1) clonal complexes CC1, CC3 and CC4; with
      eST1 and eST3 lineages being highly represented. In contrast, type IA(2) strains
      were recovered at a rate similar to type IB and II organisms. Ophthalmic
      infections were predominately associated with type IA(1) and IA(2) strains, while
      type IB and II were more frequently recovered from soft tissue and retrieved
      medical devices. Strains with rRNA mutations conferring resistance to antibiotics
      used in acne treatment were dominated by eST3, with some evidence for
      intercontinental spread. In contrast, despite its high association with acne,
      only a small number of resistant CC1 eSTs were identified. A number of eSTs were
      only recovered from healthy skin, particularly eSTs representing CC72 (type II)
      and CC77 (type III). Collectively our data lends support to the view that
      pathogenic versus truly commensal lineages of P. acnes may exist. This is likely
      to have important therapeutic and diagnostic implications.

PMID- 22859990
TI  - Can attention be confined to just part of a moving object? Revisiting target
      distractor merging in multiple object tracking.
AB  - While it was initially thought that attention was space-based, more recent work
      has shown that attention can also be object-based, in that observers find it
      easier to attend to different parts of the same object than to different parts of
      different objects. Such studies have shown that attention more easily spreads
      throughout an object than between objects. However, it is not known to what
      extent attention can be confined to just part of an object and to what extent
      attending to part of an object necessarily causes the entire object to be
      attended. We have investigated this question in the context of the multiple
      object tracking paradigm in which subjects are shown a scene containing a number
      of identical moving objects and asked to mentally track a subset of them, the
      targets, while not tracking the remainder, the distractors. Previous work has
      shown that joining each target to a distractor by a solid connector so that each
      target-distractor pair forms a single physical object, a technique known as
      target-distractor merging, makes it hard to track the targets, suggesting that
      attention cannot be restricted to just parts of objects. However, in that study
      the target-distractor pairs continuously changed length, which in itself would
      have made tracking difficult. Here we show that it remains difficult to track the
      targets even when the target-distractor pairs do not change length and even when
      the targets can be differentiated from the connectors that join them to the
      distractors. Our experiments suggest that it is hard to confine attention to just
      parts of objects, at least in the case of moving objects.

PMID- 22859989
TI  - Comparison of the fecal microbiota of healthy horses and horses with colitis by
      high throughput sequencing of the V3-V5 region of the 16S rRNA gene.
AB  - The intestinal tract houses one of the richest and most complex microbial
      populations on the planet, and plays a critical role in health and a wide range
      of diseases. Limited studies using new sequencing technologies in horses are
      available. The objective of this study was to characterize the fecal microbiome
      of healthy horses and to compare the fecal microbiome of healthy horses to that
      of horses with undifferentiated colitis. A total of 195,748 sequences obtained
      from 6 healthy horses and 10 horses affected by undifferentiated colitis were
      analyzed. Firmicutes predominated (68%) among healthy horses followed by
      Bacteroidetes (14%) and Proteobacteria (10%). In contrast, Bacteroidetes (40%)
      was the most abundant phylum among horses with colitis, followed by Firmicutes
      (30%) and Proteobacteria (18%). Healthy horses had a significantly higher
      relative abundance of Actinobacteria and Spirochaetes while horses with colitis
      had significantly more Fusobacteria. Members of the Clostridia class were more
      abundant in healthy horses. Members of the Lachnospiraceae family were the most
      frequently shared among healthy individuals. The species richness reported here
      indicates the complexity of the equine intestinal microbiome. The predominance of
      Clostridia demonstrates the importance of this group of bacteria in healthy
      horses. The marked differences in the microbiome between healthy horses and
      horses with colitis indicate that colitis may be a disease of gut dysbiosis,
      rather than one that occurs simply through overgrowth of an individual pathogen.

PMID- 22859991
TI  - Trends in the incidence of lower extremity amputations in people with and without
      diabetes over a five-year period in the Republic of Ireland.
AB  - AIMS: To describe trends in the incidence of non-traumatic amputations among
      people with and without diabetes and estimate the relative risk of an individual
      with diabetes undergoing a lower extremity amputation compared to an individual
      without diabetes in the Republic of Ireland. METHODS: All adults who underwent a
      nontraumatic amputation during 2005 to 2009 were identified using HIPE (Hospital
      In-patient Enquiry) data. Participants were classified as having diabetes or not
      having diabetes. Incidence rates were calculated using the number of discharges
      for diabetes and non-diabetes related lower extremity amputations as the
      numerator and estimates of the resident population with and without diabetes as
      the denominator. Age-adjusted incidence rates were used for trend analysis.
      RESULTS: Total diabetes-related amputation rates increased non-significantly
      during the study period; 144.2 in 2005 to 175.7 in 2009 per 100,000 people with
      diabetes (p = 0.11). Total non-diabetes related amputation rates dropped non
      significantly from 12.0 in 2005 to 9.2 in 2009 per 100,000 people without
      diabetes (p = 0.16). An individual with diabetes was 22.3 (95% CI 19.1-26.1)
      times more likely to undergo a nontraumatic amputation than an individual without
      diabetes in 2005 and this did not change significantly by 2009. DISCUSSION: This
      study provides the first national estimate of lower extremity amputation rates in
      the Republic of Ireland. Diabetes-related amputation rates have remained steady
      despite an increase in people with diabetes. These estimates provide a base-line
      and will allow follow-up over time.

PMID- 22859993
TI  - Potential influences of climate and nest structure on spotted owl reproductive
      success: a biophysical approach.
AB  - Many bird species do not make their own nests; therefore, selection of existing
      sites that provide adequate microclimates is critical. This is particularly true
      for owls in north temperate climates that often nest early in the year when
      inclement weather is common. Spotted owls use three main types of nest
      structures, each of which are structurally distinct and may provide varying
      levels of protection to the eggs or young. We tested the hypothesis that spotted
      owl nest configuration influences nest microclimate using both experimental and
      observational data. We used a wind tunnel to estimate the convective heat
      transfer coefficient (h(c)) of eggs in 25 potential nest configurations that
      mimicked 2 nest types (top-cavity and platform nests), at 3 different wind
      speeds. We then used the estimates of h(c) in a biophysical heat transfer model
      to estimate how long it would take unattended eggs to cool from incubation
      temperature (~36  degrees C) to physiological zero temperature (PZT; ~26  degrees
      C) under natural environmental conditions. Our results indicated that the
      structural configuration of nests influences the cooling time of the eggs inside
      those nests, and hence, influences the nest microclimate. Estimates of time to
      PZT ranged from 10.6 minutes to 33.3 minutes. Nest configurations that were most
      similar to platform nests always had the fastest egg cooling times, suggesting
      that platform nests were the least protective of those nests we tested. Our field
      data coupled with our experimental results suggested that nest choice is
      important for the reproductive success of owls during years of inclement weather
      or in regions characterized by inclement weather during the nesting season.

PMID- 22859992
TI  - Development of a high-throughput assay for identifying inhibitors of TBK1 and
      IKKepsilon.
AB  - IKKepsilon and TBK1 are noncanonical IKK family members which regulate
      inflammatory signaling pathways and also play important roles in oncogenesis.
      However, few inhibitors of these kinases have been identified. While the
      substrate specificity of IKKepsilon has recently been described, the substrate
      specificity of TBK1 is unknown, hindering the development of high-throughput
      screening technologies for inhibitor identification. Here, we describe the
      optimal substrate phosphorylation motif for TBK1, and show that it is identical
      to the phosphorylation motif previously described for IKKepsilon. This
      information enabled the design of an optimal TBK1/IKKepsilon substrate peptide
      amenable to high-throughput screening and we assayed a 6,006 compound library
      that included 4,727 kinase-focused compounds to discover in vitro inhibitors of
      TBK1 and IKKepsilon. 227 compounds in this library inhibited TBK1 at a
      concentration of 10 uM, while 57 compounds inhibited IKKepsilon. Together, these
      data describe a new high-throughput screening assay which will facilitate the
      discovery of small molecule TBK1/IKKepsilon inhibitors possessing therapeutic
      potential for both inflammatory diseases and cancer.

PMID- 22859994
TI  - Neuronal transcription factors induce conversion of human glioma cells to neurons
      and inhibit tumorigenesis.
AB  - Recent findings have demonstrated that the overexpression of lineage-specific
      transcription factors induces cell fate changes among diverse cell types. For
      example, neurons can be generated from mouse and human fibroblasts. It is well
      known that neurons are terminally differentiated cells that do not divide.
      Therefore, we consider how to induce glioma cells to become neurons by
      introducing transcription factors. Here, we describe the efficient generation of
      induced neuronal (iN) cells from glioma cells by the infection with three
      transcription factors: Ascl1, Brn2 and Ngn2 (ABN). iN cells expressed multiple
      neuronal markers and fired action potentials, similar to the properties of
      authentic neurons. Importantly, the proliferation of glioma cells following ABN
      overexpression was dramatically inhibited in both in vitro and in vivo
      experiments. In addition, iN cells that originated from human glioma cells did
      not continue to grow when they were sorted and cultured in vitro. The strategies
      by which glioma cells are induced to become neurons may be used to clinically
      study methods for inhibiting tumor growth.

PMID- 22859995
TI  - Who uses glucosamine and why? A study of 266,848 Australians aged 45 years and
      older.
AB  - OBJECTIVES: There has been a dramatic increase in the use of complementary
      medicines over recent decades. Glucosamine is one of the most commonly used
      complementary medicines in Western societies. An understanding of glucosamine
      consumption is of significance for public health and future health promotion.
      This paper, drawing upon the largest dataset to date with regards to glucosamine
      use (n = 266,844), examines the use and users of glucosamine amongst a sample of
      older Australians. DESIGN: Analysis of the self-reported data on use of
      glucosamine, demographics and health status as extracted from the dataset of the
      45 and Up Study, which is the largest study of healthy ageing ever undertaken in
      the Southern Hemisphere involving over 265,000 participants aged 45 and over.
      RESULTS: Analysis reveals that 58,630 (22.0%) participants reported using
      glucosamine in the 4 weeks prior to the survey. Use was higher for those who were
      female, non-smokers, residing in inner/outer regional areas, with higher income
      and private health insurance. Of all the health conditions examined only
      osteoarthritis was positively associated with use of glucosamine, while cancer,
      heart attack or angina and other heart disease were all negatively associated
      with glucosamine use. CONCLUSIONS: This study suggests that a considerable
      proportion of the Australia population aged 45 and over consume glucosamine.
      There is a need for health care practitioners to enquire with their patients
      about their use of glucosamine and for further attention to be directed to
      providing good quality information for patients and providers with regards to
      glucosamine products.

PMID- 22859996
TI  - Comparing the MicroRNA spectrum between serum and plasma.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that regulate various biological
      processes, primarily through interaction with messenger RNAs. The levels of
      specific, circulating miRNAs in blood have been shown to associate with various
      pathological conditions including cancers. These miRNAs have great potential as
      biomarkers for various pathophysiological conditions. In this study we focused on
      different sample types' effects on the spectrum of circulating miRNA in blood.
      Using serum and corresponding plasma samples from the same individuals, we
      observed higher miRNA concentrations in serum samples compared to the
      corresponding plasma samples. The difference between serum and plasma miRNA
      concentration showed some associations with miRNA from platelets, which may
      indicate that the coagulation process may affect the spectrum of extracellular
      miRNA in blood. Several miRNAs also showed platform dependent variations in
      measurements. Our results suggest that there are a number of factors that might
      affect the measurement of circulating miRNA concentration. Caution must be taken
      when comparing miRNA data generated from different sample types or measurement
      platforms.

PMID- 22859997
TI  - Diabetes care provision in UK primary care practices.
AB  - BACKGROUND: Although most people with Type 2 diabetes receive their diabetes care
      in primary care, only a limited amount is known about the quality of diabetes
      care in this setting. We investigated the provision and receipt of diabetes care
      delivered in UK primary care. METHODS: Postal surveys with all healthcare
      professionals and a random sample of 100 patients with Type 2 diabetes from 99 UK
      primary care practices. RESULTS: 326/361 (90.3%) doctors, 163/186 (87.6%) nurses
      and 3591 patients (41.8%) returned a questionnaire. Clinicians reported giving
      advice about lifestyle behaviours (e.g. 88% would routinely advise about calorie
      restriction; 99.6% about increasing exercise) more often than patients reported
      having received it (43% and 42%) and correlations between clinician and patient
      report were low. Patients' reported levels of confidence about managing their
      diabetes were moderately high; a median (range) of 21% (3% to 39%) of patients
      reporting being not confident about various areas of diabetes self-management.
      CONCLUSIONS: Primary care practices have organisational structures in place and
      are, as judged by routine quality indicators, delivering high quality care. There
      remain evidence-practice gaps in the care provided and in the self confidence
      that patients have for key aspects of self management and further research is
      needed to address these issues. Future research should use robust designs and
      appropriately designed studies to investigate how best to improve this situation.

PMID- 22859998
TI  - Coevolutionary constraints? The environment alters tripartite interaction traits
      in a legume.
AB  - Third party species, which interact with one or both partners of a pairwise
      species interaction, can shift the ecological costs and the evolutionary
      trajectory of the focal interaction. Shared genes that mediate a host's
      interactions with multiple partners have the potential to generate evolutionary
      constraints, making multi-player interactions critical to our understanding of
      the evolution of key interaction traits. Using a field quantitative genetics
      approach, we studied phenotypic and genetic correlations among legume traits for
      rhizobium and herbivore interactions in two light environments. Shifts in plant
      biomass allocation mediated negative phenotypic correlations between symbiotic
      nodule number and herbivory in the field, whereas positive genetic covariances
      suggested shared genetic pathways between nodulation and herbivory response.
      Trait variance-covariance (G) matrices were not equal in sun and shade, but
      nevertheless responses to independent and correlated selection are expected to be
      similar in both environments. Interactions between plants and aboveground
      antagonists might alter the evolutionary potential of traits mediating
      belowground mutualisms (and vice versa). Thus our understanding of legume
      rhizobium genetics and coevolution may be incomplete without a grasp of how these
      networks overlap with other plant interactions.

PMID- 22860000
TI  - Genetic and physical mapping of candidate genes for resistance to Fusarium
      oxysporum f.sp. tracheiphilum race 3 in cowpea [Vigna unguiculata (L.) Walp].
AB  - Fusarium oxysporum f.sp. tracheiphilum (Fot) is a soil-borne fungal pathogen that
      causes vascular wilt disease in cowpea. Fot race 3 is one of the major pathogens
      affecting cowpea production in California. Identification of Fot race 3
      resistance determinants will expedite delivery of improved cultivars by replacing
      time-consuming phenotypic screening with selection based on perfect markers,
      thereby generating successful cultivars in a shorter time period. Resistance to
      Fot race 3 was studied in the RIL population California Blackeye 27 (resistant) x
      24-125B-1 (susceptible). Biparental mapping identified a Fot race 3 resistance
      locus, Fot3-1, which spanned 3.56 cM on linkage group one of the CB27 x 24-125B-1
      genetic map. A marker-trait association narrowed the resistance locus to a 1.2 cM
      region and identified SNP marker 1_1107 as co-segregating with Fot3-1 resistance.
      Macro and microsynteny was observed for the Fot3-1 locus region in Glycine max
      where six disease resistance genes were observed in the two syntenic regions of
      soybean chromosomes 9 and 15. Fot3-1 was identified on the cowpea physical map on
      BAC clone CH093L18, spanning approximately 208,868 bp on BAC contig250. The Fot3
      1 locus was narrowed to 0.5 cM distance on the cowpea genetic map linkage group
      6, flanked by SNP markers 1_0860 and 1_1107. BAC clone CH093L18 was sequenced and
      four cowpea sequences with similarity to leucine-rich repeat serine/threonine
      protein kinases were identified and are cowpea candidate genes for the Fot3-1
      locus. This study has shown how readily candidate genes can be identified for
      simply inherited agronomic traits when appropriate genetic stocks and integrated
      genomic resources are available. High co-linearity between cowpea and soybean
      genomes illustrated that utilizing synteny can transfer knowledge from a
      reference legume to legumes with less complete genomic resources. Identification
      of Fot race 3 resistance genes will enable transfer into high yielding cowpea
      varieties using marker-assisted selection (MAS).

PMID- 22859999
TI  - Altered A-to-I RNA editing in human embryogenesis.
AB  - Post-transcriptional events play an important role in human development. The
      question arises as to whether Adenosine to Inosine RNA editing, catalyzed by the
      ADAR (Adenosine Deaminase acting on RNA) enzymes, differs in human embryogenesis
      and in adulthood. We tested the editing of various target genes in coding (FLNA,
      BLCAP, CYFIP2) and non-coding sequences at their Alu elements (BRCA1, CARD11,
      RBBP9, MDM4, FNACC), as well as the transcriptional levels of the ADAR1 enzymes.
      This analysis was performed on five fetal and adult human tissues: brain, heart,
      liver, kidney, and spleen, as well as on human embryonic stem cells (hESCs),
      which represent the blastocyst stage in early human development. Our results show
      substantially greater editing activity for most adult tissue samples relative to
      fetal ones, in six of the eight genes tested. To test the effect of reduced A-to
      I RNA editing activity in early human development we used human embryonic stem
      cells (hESCs) as a model and tried to generate hESC clones that overexpress the
      ADAR1-p110 isoform. We were unable to achieve overexpression of ADAR1-p110 by
      either transfection or lentiviral infection, though we easily generated hESC
      clones that expressed the GFP transgene and overexpressed ADAR1-p110 in 293T
      cells and in primary human foreskin fibroblast (HFF) cells. Moreover, in contrast
      to the expected overexpression of ADAR1-p110 protein following its introduction
      into hESCs, the expression levels of this protein decreased dramatically 24-48 hr
      post infection. Similar results were obtained when we tried to overexpress ADAR1
      p110 in pluripotent embryonal carcinoma cells. This suggests that ADAR1 protein
      is substantially regulated in undifferentiated pluripotent hESCs. Overall, our
      data suggest that A-to-I RNA editing plays a critical role during early human
      development.

PMID- 22860001
TI  - Antibodies to the alpha1-adrenergic receptor cause vascular impairments in rat
      brain as demonstrated by magnetic resonance angiography.
AB  - BACKGROUND: Circulating agonistic autoantibodies acting at G protein-coupled
      receptors have been associated with numerous sever pathologies in humans.
      Antibodies directed predominantly against the alpha(1)-adrenergig receptor were
      detected in patients suffering from widespread diseases such as hypertension and
      type 2 diabetes. Their deleterious action has been demonstrated for peripheral
      organs. We postulate that antibodies to the alpha(1)-adrenergig receptor are
      relevant pathomolecules in diseases of the central nervous system associated with
      vascular impairments. METHODOLOGY/PRINCIPAL FINDINGS: Using a rat model we
      studied the long-term action of antibodies against the alpha(1)-adrenergig
      receptor either induced by immunization with a receptor peptide or applied by
      intravenous injection. The vasculature in the rat brains was investigated by time
      of-flight magnetic resonance angiography using a 9.4 Tesla small animal MR
      imaging system. Visual examination of maximum-intensity-projections (MIPs) of
      brain angiographs revealed the development of vascular defects in antibody-
      exposed animals between three and eight months of treatment. Relative vascular
      areas were derived from representative MIP image sections by grayscale analysis
      and used to form an index of vascular circulation. Animals exposed to the action
      of alpha(1)-adrenergig receptor antibodies showed significantly reduced vascular
      areas (p<0.05). Calculated index values indicated attenuated blood flow in both
      antibody-treated cohorts compared to their respective controls reaching with
      (relative units +/- standard error, n = 10) 0.839 +/- 0.026 versus 0.919 +/-
      0.026 statistical significance (p<0.05) for peptide-immunized rats.
      CONCLUSION/SIGNIFICANCE: We present evidence that antibodies to the alpha(1)
      adrenergig receptor cause cerebrovascular impairments in the rat. Our findings
      suggest the pathological significance of these antibodies in pathologies of the
      human central nervous system linked to impairments of brain vasculature such as
      stroke and dementia.

PMID- 22860002
TI  - A Genomic Island in Salmonella enterica ssp. salamae provides new insights on the
      genealogy of the locus of enterocyte effacement.
AB  - The genomic island encoding the locus of enterocyte effacement (LEE) is an
      important virulence factor of the human pathogenic Escherichia coli. LEE
      typically encodes a type III secretion system (T3SS) and secreted effectors
      capable of forming attaching and effacing lesions. Although prominent in the
      pathogenic E. coli such as serotype O157:H7, LEE has also been detected in
      Citrobacter rodentium, E. albertii, and although not confirmed, it is likely to
      also be in Shigella boydii. Previous phylogenetic analysis of LEE indicated the
      genomic island was evolving through stepwise acquisition of various components.
      This study describes a new LEE region from two strains of Salmonella enterica
      subspecies salamae serovar Sofia along with a phylogenetic analysis of LEE that
      provides new insights into the likely evolution of this genomic island. The
      Salmonella LEE contains 36 of the 41 genes typically observed in LEE within a
      genomic island of 49, 371 bp that encodes a total of 54 genes. A phylogenetic
      analysis was performed on the entire T3SS and four T3SS genes (escF, escJ, escN,
      and escV) to elucidate the genealogy of LEE. Phylogenetic analysis inferred that
      the previously known LEE islands are members of a single lineage distinct from
      the new Salmonella LEE lineage. The previously known lineage of LEE diverged
      between islands found in Citrobacter and those in Escherichia and Shigella.
      Although recombination and horizontal gene transfer are important factors in the
      genealogy of most genomic islands, the phylogeny of the T3SS of LEE can be
      interpreted with a bifurcating tree. It seems likely that the LEE island entered
      the Enterobacteriaceae through horizontal gene transfer as a single unit, rather
      than as separate subsections, which was then subjected to the forces of both
      mutational change and recombination.

PMID- 22860003
TI  - Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for
      gastric cancer detection.
AB  - BACKGROUND: MicroRNAs (miRNAs), endogenous small non-coding RNAs, are stably
      detected in human plasma. Early diagnosis of gastric cancer (GC) is very
      important to improve the therapy effect and prolong the survival of patients. We
      aimed to identify whether four miRNAs (miR-223, miR-21, miR-218 and miR-25)
      closely associated with the tumorigenesis or metastasis of GC can serve as novel
      potential biomarkers for GC detection. METHODOLOGY: We initially measured the
      plasma levels of the four miRNAs in 10 GC patients and 10 healthy control
      subjects by quantitative reverse transcription polymerase chain reaction (qRT
      PCR), and then compared plasma miRNA results with the expressions in cancer
      tissues from eight GC patients. Finally, the presence of miR-223, miR-21 and miR
      218 in the plasma was validated in 60 GC patients and 60 healthy control
      subjects, and the areas under the receiver operating characteristic (ROC) curves
      of these miRNAs were analyzed. RESULTS: We found that the plasma levels of miR
      223 (P<0.001) and miR-21 (P<0.001) were significantly higher in GC patients than
      in healthy controls, while miR-218 (P<0.001) was significantly lower. The ROC
      analyses yielded the AUC values of 0.9089 for miR-223, 0.7944 for miR-21 and
      0.7432 for miR-218, and combined ROC analysis revealed the highest AUC value of
      0.9531 in discriminating GC patients from healthy controls. Moreover, the plasma
      levels of miR-223 (P<0.001) and miR-21 (P = 0.003) were significantly higher in
      GC patients with stage I than in healthy controls. Furthermore, the plasma levels
      of miR-223 were significantly higher in GC patients with helicobacter pylori (Hp)
      infection than those without (P = 0.014), and significantly higher in healthy
      control subjects with Hp infection than those without (P = 0.016). CONCLUSIONS:
      Plasma miR-223, miR-21 and miR-218 are novel potential biomarkers for GC
      detection.

PMID- 22860004
TI  - Deep sequencing-based transcriptome analysis of chicken spleen in response to
      avian pathogenic Escherichia coli (APEC) infection.
AB  - Avian pathogenic Escherichia coli (APEC) leads to economic losses in poultry
      production and is also a threat to human health. The goal of this study was to
      characterize the chicken spleen transcriptome and to identify candidate genes for
      response and resistance to APEC infection using Solexa sequencing. We obtained
      14422935, 14104324, and 14954692 Solexa read pairs for non-challenged (NC),
      challenged-mild pathology (MD), and challenged-severe pathology (SV),
      respectively. A total of 148197 contigs and 98461 unigenes were assembled, of
      which 134949 contigs and 91890 unigenes match the chicken genome. In total, 12272
      annotated unigenes take part in biological processes (11664), cellular components
      (11927), and molecular functions (11963). Summing three specific contrasts, 13650
      significantly differentially expressed unigenes were found in NC Vs. MD (6844),
      NC Vs. SV (7764), and MD Vs. SV (2320). Some unigenes (e.g. CD148, CD45 and LCK)
      were involved in crucial pathways, such as the T cell receptor (TCR) signaling
      pathway and microbial metabolism in diverse environments. This study facilitates
      understanding of the genetic architecture of the chicken spleen transcriptome,
      and has identified candidate genes for host response to APEC infection.

PMID- 22860005
TI  - TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains
      expression in a castration resistant subpopulation.
AB  - Genomic rearrangements commonly occur in many types of cancers and often initiate
      or alter the progression of disease. Here we describe an in vivo mouse model that
      recapitulates the most frequent rearrangement in prostate cancer, the fusion of
      the promoter region of TMPRSS2 with the coding region of the transcription
      factor, ERG. A recombinant bacterial artificial chromosome including an extended
      TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in
      mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS
      fractionated prostate cell populations. In addition to the anticipated expression
      in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi)/EpCAM(+)
      basal/progenitor fraction, where expanded numbers of clonogenic self-renewing
      progenitors were found, as assayed by in vitro sphere formation. These clonogenic
      cells increased intrinsic self renewal in subsequent generations. In addition,
      ERG dependent self-renewal and invasion in vitro was demonstrated in prostate
      cell lines derived from the model. Clinical studies have suggested that the
      TMPRSS2-ERG translocation occurs early in prostate cancer development. In the
      model described here, the presence of the TMPRSS2-ERG fusion alone was not
      transforming but synergized with heterozygous Pten deletion to promote PIN. Taken
      together, these data suggest that one function of TMPRSS2-ERG is the expansion of
      self-renewing cells, which may serve as targets for subsequent mutations. Primary
      prostate epithelial cells demonstrated increased post transcriptional turnover of
      ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from
      a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression
      occurred in both castration-sensitive and resistant prostate epithelial
      subpopulations, suggesting the existence of androgen-independent mechanisms of
      TMPRSS2 expression in prostate epithelium.

PMID- 22860006
TI  - Prevalence and predictors of major depression in HIV-infected patients on
      antiretroviral therapy in Bamenda, a semi-urban center in Cameroon.
AB  - Recent blue-ribbon panel reports have concluded that HIV treatment programs in
      less wealthy countries must integrate mental health identification and treatment
      into normal HIV clinical care and that research on mental health and HIV in these
      settings should be a high priority. We assessed the epidemiology of depression in
      HIV patients on antiretroviral therapy in a small urban setting in Cameroon by
      administering a structured interview for depression to 400 patients consecutively
      attending the Bamenda Regional Hospital AIDS Treatment Center. One in five
      participants met lifetime criteria for MDD, and 7% had MDD within the prior year.
      Only 33% had ever spoken with a health professional about depression, and 12%
      reported ever having received depression treatment that was helpful or effective.
      Over 2/3 with past-year MDD had severe or very severe episodes. The number of
      prior depressive episodes and the number of HIV symptoms were the strongest
      predictors of past-year MDD. The prevalence of MDD in Cameroon is as high as that
      of other HIV-associated conditions, such as tuberculosis and Hepatitis B virus,
      whose care is incorporated into World Health Organization guidelines. The
      management of depression needs to be incorporated in HIV-care guidelines in
      Cameroon and other similar settings.

PMID- 22860007
TI  - Rapid one-step selection method for generating nucleic acid aptamers: development
      of a DNA aptamer against alpha-bungarotoxin.
AB  - BACKGROUND: Nucleic acids based therapeutic approaches have gained significant
      interest in recent years towards the development of therapeutics against many
      diseases. Recently, research on aptamers led to the marketing of Macugen(r), an
      inhibitor of vascular endothelial growth factor (VEGF) for the treatment of age
      related macular degeneration (AMD). Aptamer technology may prove useful as a
      therapeutic alternative against an array of human maladies. Considering the
      increased interest in aptamer technology globally that rival antibody mediated
      therapeutic approaches, a simplified selection, possibly in one-step, technique
      is required for developing aptamers in limited time period. PRINCIPAL FINDINGS:
      Herein, we present a simple one-step selection of DNA aptamers against alpha
      bungarotoxin. A toxin immobilized glass coverslip was subjected to nucleic acid
      pool binding and extensive washing followed by PCR enrichment of the selected
      aptamers. One round of selection successfully identified a DNA aptamer sequence
      with a binding affinity of 7.58 uM. CONCLUSION: We have demonstrated a one-step
      method for rapid production of nucleic acid aptamers. Although the reported
      binding affinity is in the low micromolar range, we believe that this could be
      further improved by using larger targets, increasing the stringency of selection
      and also by combining a capillary electrophoresis separation prior to the one
      step selection. Furthermore, the method presented here is a user-friendly, cheap
      and an easy way of deriving an aptamer unlike the time consuming conventional
      SELEX-based approach. The most important application of this method is that
      chemically-modified nucleic acid libraries can also be used for aptamer selection
      as it requires only one enzymatic step. This method could equally be suitable for
      developing RNA aptamers.

PMID- 22860008
TI  - Erwinia amylovora CRISPR elements provide new tools for evaluating strain
      diversity and for microbial source tracking.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) comprise a
      family of short DNA repeat sequences that are separated by non repetitive spacer
      sequences and, in combination with a suite of Cas proteins, are thought to
      function as an adaptive immune system against invading DNA. The number of CRISPR
      arrays in a bacterial chromosome is variable, and the content of each array can
      differ in both repeat number and in the presence or absence of specific spacers.
      We utilized a comparative sequence analysis of CRISPR arrays of the plant
      pathogen Erwinia amylovora to uncover previously unknown genetic diversity in
      this species. A total of 85 E. amylovora strains varying in geographic isolation
      (North America, Europe, New Zealand, and the Middle East), host range, plasmid
      content, and streptomycin sensitivity/resistance were evaluated for CRISPR array
      number and spacer variability. From these strains, 588 unique spacers were
      identified in the three CRISPR arrays present in E. amylovora, and these arrays
      could be categorized into 20, 17, and 2 patterns types, respectively. Analysis of
      the relatedness of spacer content differentiated most apple and pear strains
      isolated in the eastern U.S. from western U.S. strains. In addition, we
      identified North American strains that shared CRISPR genotypes with strains
      isolated on other continents. E. amylovora strains from Rubus and Indian hawthorn
      contained mostly unique spacers compared to apple and pear strains, while strains
      from loquat shared 79% of spacers with apple and pear strains. Approximately 23%
      of the spacers matched known sequences, with 16% targeting plasmids and 5%
      targeting bacteriophage. The plasmid pEU30, isolated in E. amylovora strains from
      the western U.S., was targeted by 55 spacers. Lastly, we used spacer patterns and
      content to determine that streptomycin-resistant strains of E. amylovora from
      Michigan were low in diversity and matched corresponding streptomycin-sensitive
      strains from the background population.

PMID- 22860009
TI  - Effect of substrate stiffness on early mouse embryo development.
AB  - It is becoming increasingly clear that cells are remarkably sensitive to the
      biophysical cues of their microenvironment and that these cues play a significant
      role in influencing their behaviors. In this study, we investigated whether the
      early pre-implantation embryo is sensitive to mechanical cues, i.e. the
      elasticity of the culture environment. To test this, we have developed a new
      embryo culture system where the mechanical properties of the embryonic
      environment can be precisely defined. The contemporary standard environment for
      embryo culture is the polystyrene petri dish (PD), which has a stiffness (1 GPa)
      that is six orders of magnitude greater than the uterine epithelium (1 kPa). To
      approximate more closely the mechanical aspects of the in vivo uterine
      environment we used polydimethyl-siloxane (PDMS) or fabricated 3D type I collagen
      gels (1 kPa stiffness, Col-1k group). Mouse embryo development on alternate
      substrates was compared to that seen on the petri dish; percent development,
      hatching frequency, and cell number were observed. Our results indicated that
      embryos are sensitive to the mechanical environment on which they are cultured.
      Embryos cultured on Col-1k showed a significantly greater frequency of
      development to 2-cell (68 +/- 15% vs. 59 +/- 18%), blastocyst (64 +/- 9.1% vs. 50
      +/- 18%) and hatching blastocyst stages (54 +/- 25% vs. 21 +/- 16%) and an
      increase in the number of trophectodermal cell (TE,65 +/- 13 vs. 49 +/- 12 cells)
      compared to control embryos cultured in PD (mean +/- S.D.; p<.01). Embryos
      cultured on Col-1k and PD were transferred to recipient females and observed on
      embryonic day 12.5. Both groups had the same number of fetuses, however the
      placentas of the Col-1k fetuses were larger than controls, suggesting a continued
      effect of the preimplantation environment. In summary, characteristics of the
      preimplantation microenvironment affect pre- and post-implantation growth.

PMID- 22860010
TI  - Proteomic changes in rat spermatogenesis in response to in vivo androgen
      manipulation; impact on meiotic cells.
AB  - The production of mature sperm is reliant on androgen action within the testis,
      and it is well established that androgens act on receptors within the somatic
      Sertoli cells to stimulate male germ cell development. Mice lacking Sertoli cell
      androgen receptors (AR) show late meiotic germ cell arrest, suggesting Sertoli
      cells transduce the androgenic stimulus co-ordinating this essential step in
      spermatogenesis. This study aimed to identify germ cell proteins responsive to
      changes in testicular androgen levels and thereby elucidate mechanisms by which
      androgens regulate meiosis. Testicular androgen levels were suppressed for 9
      weeks using testosterone and estradiol-filled silastic implants, followed by a
      short period of either further androgen suppression (via an AR antagonist) or the
      restoration of intratesticular testosterone levels. Comparative proteomics were
      performed on protein extracts from enriched meiotic cell preparations from adult
      rats undergoing androgen deprivation and replacement in vivo. Loss of androgenic
      stimulus caused changes in proteins with known roles in meiosis (including Nasp
      and Hsp70-2), apoptosis (including Diablo), cell signalling (including 14-3-3
      isoforms), oxidative stress, DNA repair, and RNA processing. Immunostaining for
      oxidised DNA adducts confirmed spermatocytes undergo oxidative stress-induced DNA
      damage during androgen suppression. An increase in PCNA and an associated
      ubiquitin-conjugating enzyme (Ubc13) suggested a role for PCNA-mediated
      regulation of DNA repair pathways in spermatocytes. Changes in cytoplasmic SUMO1
      localisation in spermatocytes were paralleled by changes in the levels of free
      SUMO1 and of a subunit of its activating complex, suggesting sumoylation in
      spermatocytes is modified by androgen action on Sertoli cells. We conclude that
      Sertoli cells, in response to androgens, modulate protein translation and post
      translational events in spermatocytes that impact on their metabolism, survival,
      and completion of meiosis.

PMID- 22860011
TI  - Depletion of c-Rel from cytokine gene promoters is required for chromatin
      reassembly and termination of gene responses to T cell activation.
AB  - The role of the Nuclear Factor kappaB (NF-kappaB) transcription factor family in
      T cell function has been well described. The c-Rel family member is of particular
      importance in initiating T cell responses to antigen and regulating activation of
      inflammatory cytokine genes, including the Interleukin-2 (IL-2) and Granulocyte
      macrophage colony stimulating factor (GM-CSF) genes. c-Rel is required for
      chromatin remodeling of these gene promoters, which involves depletion of
      histones from the promoters in response to T cell activating signals. These
      chromatin remodeling events precede transcriptional activation of the genes. The
      subsequent down-regulation of cytokine gene expression is important in the
      termination of an immune response and here we examine this process at the murine
      GM-CSF and IL-2 genes. We show that the cytokine mRNA levels rapidly return to
      basal levels following stimulus removal and this is associated with reassembly of
      histones onto the promoter. Histone reassembly at the GM-CSF and IL-2 promoters
      occurs concomitantly with depletion of RelA, c-Rel and RNA polymerase II from the
      promoters. Furthermore we show that transcriptional down-regulation and chromatin
      reassembly is dependent on depletion of c-Rel from the nucleus, and that this is
      regulated by the nuclear translocation of the NF-kappaB inhibitor, IkappaBalpha.
      The nuclear activation of c-Rel therefore not only regulates the initiation of GM
      CSF and IL-2 gene activation in response to T cell activation, but also the
      termination of these gene responses following the removal of the activating
      signal.

PMID- 22860013
TI  - Harmonization process and reliability assessment of anthropometric measurements
      in the elderly EXERNET multi-centre study.
AB  - BACKGROUND: The elderly EXERNET multi-centre study aims to collect normative
      anthropometric data for old functionally independent adults living in Spain.
      PURPOSE: To describe the standardization process and reliability of the
      anthropometric measurements carried out in the pilot study and during the final
      workshop, examining both intra- and inter-rater errors for measurements.
      MATERIALS AND METHODS: A total of 98 elderly from five different regions
      participated in the intra-rater error assessment, and 10 different seniors living
      in the city of Toledo (Spain) participated in the inter-rater assessment. We
      examined both intra- and inter-rater errors for heights and circumferences.
      RESULTS: For height, intra-rater technical errors of measurement (TEMs) were
      smaller than 0.25 cm. For circumferences and knee height, TEMs were smaller than
      1 cm, except for waist circumference in the city of Caceres. Reliability for
      heights and circumferences was greater than 98% in all cases. Inter-rater TEMs
      were 0.61 cm for height, 0.75 cm for knee-height and ranged between 2.70 and 3.09
      cm for the circumferences measured. Inter-rater reliabilities for anthropometric
      measurements were always higher than 90%. CONCLUSION: The harmonization process,
      including the workshop and pilot study, guarantee the quality of the
      anthropometric measurements in the elderly EXERNET multi-centre study. High
      reliability and low TEM may be expected when assessing anthropometry in elderly
      population.

PMID- 22860012
TI  - Peritumoral small ephrinA5 isoform level predicts the postoperative survival in
      hepatocellular carcinoma.
AB  - BACKGROUND: EphrinA5, a member of Eph/Ephrin family, possesses two alternative
      isoforms, large ephrinA5 isoform (ephrinA5L) and small ephrinA5 isoform
      (ephrinA5S). EphrinA5L is a putative tumor suppressor in several types of human
      cancers. However, the role of ephrinA5S in hepato-carcinogenesis remains unclear.
      In this study, we evaluate the role of ephrinA5 isoforms in human hepatocellular
      carcinomas (HCC). METHODOLOGY/PRINCIPAL FINDINGS: A total of 142 paired HCCs and
      peritumoral liver tissue was examined for relative expression of ephrinA5L and
      ephrinA5S by using quantitative real-time polymerase chain reaction. We analyzed
      their expression in relation to clinical parameters, disease-free survival and
      overall survival. Functional assays were performed to dissect the possible
      underlying mechanisms. Both ephrinA5L and ephrinA5S were significantly
      downregulated in HCCs, as compared to those in peritumoral tissue (p = 0.013 and
      0.001). Univariate analysis demonstrated that ephrinA5S was positively correlated
      with old age and histological grade. In multivariate analysis, high ephrinA5S
      expression in peritumoral tissue had better disease-free survival (p = 0.002) and
      overall survival (p = 0.045) in patients with HCC after surgical resection.
      Functional analysis in HCC cell lines revealed that ephrinA5S had a more potent
      suppressive effect than ephrinA5L on cell proliferation (p<0.05) and migration
      (p<0.01). Furthermore, forced expression of both ephrinA5 isoforms in HCC cell
      lines significantly down-regulated epidermal growth factor receptor (EGFR)
      expression by promoting c-Cbl-mediated EGFR degradation.
      CONCLUSIONS/SIGNIFICANCE: EphrinA5S might be a useful prognostic biomarker for
      HCCs after surgical resection. EphrinA5, especially ephrinA5S, acts as a tumor
      suppressor in hepatocarcinogenesis. Peritumoral small ephrinA5 isoform level
      could determine the postoperative survival in hepatocellular carcinoma.

PMID- 22860015
TI  - A systematic review of comparative efficacy of treatments and controls for
      depression.
AB  - BACKGROUND: Although previous meta-analyses have examined effects of
      antidepressants, psychotherapy, and alternative therapies for depression, the
      efficacy of these treatments alone and in combination has not been systematically
      compared. We hypothesized that the differences between approved depression
      treatments and controls would be small. METHODS AND FINDINGS: The authors first
      reviewed data from Food and Drug Administration Summary Basis of Approval reports
      of 62 pivotal antidepressant trials consisting of data from 13,802 depressed
      patients. This was followed by a systematic review of data from 115 published
      trials evaluating efficacy of psychotherapies and alternative therapies for
      depression. The published depression trials consisted of 10,310 depressed
      patients. We assessed the percentage symptom reduction experienced by the
      patients based on treatment assignment. Overall, antidepressants led to greater
      symptom reduction compared to placebo among both unpublished FDA data and
      published trials (F = 38.5, df = 239, p<0.001). In the published trials we noted
      that the magnitude of symptom reduction with active depression treatments
      compared to controls was significantly larger when raters evaluating treatment
      effects were un-blinded compared to the trials with blinded raters (F = 2.17, df
      = 313, p<0.05). In the blinded trials, the combination of antidepressants and
      psychotherapy provided a slight advantage over antidepressants (p = 0.027) and
      psychotherapy (p = 0.022) alone. The magnitude of symptom reduction was greater
      with psychotherapies compared to placebo (p = 0.019), treatment-as-usual (p =
      0.012) and waiting-list (p<0.001). Differences were not seen with psychotherapy
      compared to antidepressants, alternative therapies or active intervention
      controls. CONCLUSIONS: In conclusion, the combination of psychotherapy and
      antidepressants for depression may provide a slight advantage whereas
      antidepressants alone and psychotherapy alone are not significantly different
      from alternative therapies or active intervention controls. These data suggest
      that type of treatment offered is less important than getting depressed patients
      involved in an active therapeutic program. Future research should consider
      whether certain patient profiles might justify a specific treatment modality.

PMID- 22860014
TI  - Beneficial effects on arterial stiffness and pulse-wave reflection of combined
      enalapril and candesartan in chronic kidney disease--a randomized trial.
AB  - BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in patients with
      chronic kidney disease (CKD). Inhibition of the renin-angiotensinsystem (RAS) in
      hypertension causes differential effects on central and brachial blood pressure
      (BP), which has been translated into improved outcome. The objective was to
      examine if a more complete inhibition of RAS by combining an angiotensin
      converting enzyme inhibitor (ACEI) and an angiotensin receptor antagonist (ARB)
      compared to monotherapy has an additive effect on central BP and pulse-wave
      velocity (PWV), which are known markers of CVD. METHODS: Sixty-seven CKD patients
      (mean GFR 30, range 13-59 ml/min/1.73 m(2)) participated in an open randomized
      study of 16 weeks of monotherapy with either enalapril or candesartan followed by
      8 weeks of dual blockade aiming at a total dose of 16 mg candesartan and 20 mg
      enalapril o.d. Pulse-wave measurements were performed at week 0, 8, 16 and 24 by
      the SphygmoCor device. RESULTS: Significant additive BP independent reductions
      were found after dual blockade in aortic PWV (-0.3 m/s, P<0.05) and in
      augmentation index (-2%, P<0.01) compared to monotherapy. Furthermore pulse
      pressure amplification was improved (P<0.05) and central systolic BP reduced (-6
      mmHg, P<0.01). CONCLUSIONS: Dual blockade of the RAS resulted in an additive BP
      independent reduction in pulse-wave reflection and arterial stiffness compared to
      monotherapy in CKD patients. TRIAL REGISTRATION: Clinical trial.gov NCT00235287.

PMID- 22860016
TI  - Cells expressing the C/EBPbeta isoform, LIP, engulf their neighbors.
AB  - Descriptions of various processes that lead to cell-in-cell structures have been
      reported for decades. The exact molecular mechanism(s) of their formation and the
      physiological significance of cell-in-cell structures remain poorly understood.
      We had previously shown that an isoform of the CCAAT/enhancer-binding protein
      beta (C/EBPbeta) transcription factor, liver-enriched inhibitory protein (LIP),
      induces cell death in human breast cancer cells and stimulates autophagy. Here we
      describe a non-apoptotic cell death process where LIP mediates the engulfment of
      neighboring cells. We provide evidence of LIP-mediated engulfment via DNA
      profiling, fluorescent imaging and cell sorting studies, as well as
      ultrastructure analysis of LIP-expressing MDA-MB-468 breast cancer cells. Our
      work illustrates that expression of a specific transcription factor, LIP, can
      mediate cell engulfment.

PMID- 22860017
TI  - Induction of RAGE shedding by activation of G protein-coupled receptors.
AB  - The multiligand Receptor for Advanced Glycation End products (RAGE) is involved
      in various pathophysiological processes, including diabetic inflammatory
      conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type
      I membrane protein, can proteolytically be converted by metalloproteinases ADAM10
      and MMP9 into a soluble RAGE form. Moreover, administration of recombinant
      soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE
      ligands. Therefore stimulation of RAGE shedding might have a therapeutic value
      regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is
      inducible via ligand-induced activation of G protein-coupled receptors (GPCRs).
      We chose three different GPCRs coupled to distinct signaling cascades: the V2
      vasopressin receptor (V2R) activating adenylyl cyclase, the oxytocin receptor
      (OTR) linked to phospholipase Cbeta, and the PACAP receptor (subtype PAC1)
      coupled to adenylyl cyclase, phospholipase Cbeta, calcium signaling and MAP
      kinases. We generated HEK cell lines stably coexpressing an individual GPCR and
      full-length RAGE and then investigated GPCR ligand-induced activation of RAGE
      shedding. We found metalloproteinase-mediated RAGE shedding on the cell surface
      to be inducible via ligand-specific activation of all analyzed GPCRs. By using
      specific inhibitors we have identified Ca(2+) signaling, PKCalpha/PKCbetaI,
      CaMKII, PI3 kinases and MAP kinases to be involved in PAC1 receptor-induced RAGE
      shedding. We detected an induction of calcium signaling in all our cell lines
      coexpressing RAGE and different GPCRs after agonist treatment. However, we did
      not disclose a contribution of adenylyl cyclase in RAGE shedding induction.
      Furthermore, by using a selective metalloproteinase inhibitor and siRNA-mediated
      knock-down approaches, we show that ADAM10 and/or MMP9 are playing important
      roles in constitutive and PACAP-induced RAGE shedding. We also found that
      treatment of mice with PACAP increases the amount of soluble RAGE in the mouse
      lung. Our findings suggest that pharmacological stimulation of RAGE shedding
      might open alternative treatment strategies for Alzheimers disease and diabetes
      induced inflammation.

PMID- 22860018
TI  - Differential effect of growth factors on invasion and proliferation of endocrine
      resistant breast cancer cells.
AB  - We have established several breast cancer cell lines that exhibit a permanent ER
      depleted phenotype, induced by shRNA transfection of MCF-7 cells, which afford a
      useful model for studying acquired endocrine resistance. Previously we showed
      that MDA-231 as well as ER-silenced cells could invade through simulated
      extracellular matrix components. However, the contribution of individual serum
      components responsible for cell invasion was not determined. In the present
      study, an under-agarose gel assay was used to quantitatively assess the invasive
      movement of two ER-silenced cell lines (pII and YS2.5) in comparison to the
      parental MCF-7, the ER negative MDA-231, and normal HBL100 cells, as well as a
      line that was ER-shRNA transfected but failed to exhibit ER down-regulation
      (YS1.2). We also examined the effect of the growth factors EGF, IGF-1, TGFbeta,
      PDGFC and RANTES on pII cell invasion and proliferation. All breast cancer cell
      lines which had reduced ER expression exhibited a serum-dependent invasive
      ability related to the degree of induced ER loss. TGFbeta treatment inhibited pII
      cell proliferation and enhanced their invasive ability but at a relatively high
      dose. IGF-1 and EGF enhanced pII cell proliferation, with the latter playing the
      major role in promoting cell invasion. PDGFC did not affect either process
      although it is highly expressed in pII cells. Differential effects were observed
      on activation of Akt and ERK1/2 suggesting their involvement as intracellular
      mediators of EGF induced invasion, in part through the regulation of matrix
      metalloproteinase activity. Targeting EGF receptor tyrosine kinase activity by
      erlotinib resulted in significant inhibition of both pII cell proliferation and
      directional invasion towards EGF suggesting that this drug has potential
      therapeutic usefulness for preventing spread of particularly endocrine resistant
      breast cancer.

PMID- 22860019
TI  - Nanoparticle-mediated local delivery of an antisense TGF-beta1 construct inhibits
      intimal hyperplasia in autogenous vein grafts in rats.
AB  - BACKGROUND: Intimal hyperplasia is one of the most important causes of vascular
      graft failure. Numerous studies have correlated transforming growth factor-beta1
      (TGF-beta1) with extracellular matrix (ECM) deposition, a hallmark of intimal
      thickening. PRINCIPAL FINDINGS: In the present study, we performed
      immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression
      of TGF-beta1, TGF-beta1 receptor type I (TGF-beta RI), matrix metalloproteinase-1
      (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal
      hyperplasia in grafted veins of a rat model generated by grafting a portion of
      the right internal jugular vein to the ipisiliary carotid artery. Additionally,
      we determined whether nanoparticle-mediated delivery of a TGF-beta1 antisense
      expressing construct prevented TGF-beta1 expression and intimal hyperplasia in
      grafted veins. In grafted veins, the expression of TGF-beta1 significantly
      increased on day 3 after transplantation, peaked on day 7, slightly decreased on
      day 14, and returned to baseline levels on day 28. The positive expression of TGF
      beta RI in grafted veins remarkably increased on day 7, peaked on day 14, and
      decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1
      expression increased, significantly on days 14 and 28. Nanoparticle-mediated
      delivery of a TGF-beta1 antisense-expressing construct down-regulated TGF-beta1
      expression and inhibited intimal hyperplasia in grafted veins. CONCLUSIONS: Our
      findings provide further evidence that TGF-beta1 plays an integral role in the
      development of intimal hyperplasia after vascular injury. Nanoparticle-mediated
      delivery of a TGF-beta1 antisense-expressing construct is a feasible strategy to
      target TGF-beta1-induced intimal thickening.

PMID- 22860020
TI  - Proteome analysis of the wild and YX-1 male sterile mutant anthers of wolfberry
      (Lycium barbarum L.).
AB  - Pollen development is disturbed in the early tetrad stage of the YX-1 male
      sterile mutant of wolfberry (Lycium barbarum L.). The present study aimed to
      identify differentially expressed anther proteins and to reveal their possible
      roles in pollen development and male sterility. To address this question, the
      proteomes of the wild-type (WT) and YX-1 mutant were compared. Approximately 1760
      protein spots on two-dimensional differential gel electrophoresis (2D-DIGE) gels
      were detected. A number of proteins whose accumulation levels were altered in YX
      1 compared with WT were identified by mass spectrometry and the NCBInr and
      Viridiplantae EST databases. Proteins down-regulated in YX-1 anthers include
      ascorbate peroxidase (APX), putative glutamine synthetase (GS), ATP synthase
      subunits, chalcone synthase (CHS), CHS-like, putative callose synthase catalytic
      subunit, cysteine protease, 5B protein, enoyl-ACP reductase, 14-3-3 protein and
      basic transcription factor 3 (BTF3). Meanwhile, activities of APX and GS, RNA
      expression levels of apx and atp synthase beta subunit were low in YX-1 anthers
      which correlated with the expression of male sterility. In addition, several
      carbohydrate metabolism-related and photosynthesis-related enzymes were also
      present at lower levels in the mutant anthers. In contrast, 26S proteasome
      regulatory subunits, cysteine protease inhibitor, putative S-phase Kinase
      association Protein 1(SKP1), and aspartic protease, were expressed at higher
      levels in YX-1 anthers relative to WT anthers. Regulation of wolfberry pollen
      development involves a complex network of differentially expressed genes. The
      present study lays the foundation for future investigations of gene function
      linked with wolfberry pollen development and male sterility.

PMID- 22860021
TI  - Evaluation of dynamic [18F]-FDG-PET imaging for the detection of acute post
      surgical bone infection.
AB  - Diagnosing bone infection in its acute early stage is of utmost clinical
      importance as the failure to do so results in a therapeutically recalcitrant
      chronic infection that can only be resolved with extensive surgical intervention,
      the end result often being a structurally unstable defect requiring
      reconstructive procedures. [(18)F]-FDG-PET has been extensively investigated for
      this purpose, but the results have been mixed in that, while highly sensitive,
      its specificity with respect to distinguishing between acute infection and
      sterile inflammatory processes, including normal recuperative post-surgical
      healing, is limited. This study investigated the possibility that alternative
      means of acquiring and analyzing FDG-PET data could be used to overcome this lack
      of specificity without an unacceptable loss of sensitivity. This was done in the
      context of an experimental rabbit model of post-surgical osteomyelitis with the
      objective of distinguishing between acute infection and sterile post-surgical
      inflammation. Imaging was done 7 and 14 days after surgery with continuous data
      acquisition for a 90-minute period after administration of tracer. Results were
      evaluated based on both single and dual time point data analysis. The results
      suggest that the diagnostic utility of FDG-PET is likely limited to well-defined
      clinical circumstances. We conclude that, in the complicated clinical context of
      acute post-surgical or post-traumatic infection, the diagnostic utility accuracy
      of FDG-PET is severely limited based on its focus on the increased glucose
      utilization that is generally characteristic of inflammatory processes.

PMID- 22860022
TI  - Crystal structure of TNF-alpha-inducing protein from Helicobacter pylori in
      active form reveals the intrinsic molecular flexibility for unique DNA-binding.
AB  - Tipalpha (TNF-alpha-inducing protein) from Helicobacter pylori is a carcinogenic
      effector. Studies on this protein revealed that a homodimer linked by a pair of
      intermolecular disulfide bridges (Cys25-Cys25 and Cys27-Cys27) was absolutely
      necessary for its biological functions. The activities of Tipalpha would be
      abolished when both disulfide bridges were disrupted. The crystal structures of
      Tipalpha reported to date, however, were based on inactive, monomeric mutants
      with their N-terminal, including residues Cys25 and Cys27, truncated. Here we
      report the crystal structure of H. pylori Tipalpha protein, TipalphaN(25), at
      2.2A resolution, in which Cys25 and Cys27 form a pair of inter-chain disulfide
      bridges linking an active dimer. The disulfide bridges exhibit structural
      flexibility in the present structure. A series of structure-based mutagenesis,
      biochemical assays and molecular dynamic simulations on DNA-Tipalpha interactions
      reveal that Tipalpha utilizes the dimeric interface as the DNA-binding site and
      that residues His60, Arg77 and Arg81 located at the interface are crucial for DNA
      binding. Tipalpha could bind to one ssDNA, two ssDNA or one dsDNA in experiments,
      respectively, in the native or mutant states. The unique DNA-binding activities
      of Tipalpha indicate that the intrinsic flexible nature of disulfide bridges
      could endow certain elasticity to the Tipalpha dimer for its unique
      bioactivities. The results shed light on the possible structural mechanism for
      the functional performances of Tipalpha.

PMID- 22860023
TI  - MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro.
AB  - Possession of a properly functioning innate immune system in the lung is vital to
      prevent infections due to the ongoing exposure of the lung to pathogens. While
      mechanisms of pulmonary innate immunity have been well studied, our knowledge of
      how these systems are altered in disease states, leading to increased
      susceptibility to infections, is limited. One innate immune protein in the lung,
      the pulmonary collectin SP-D, has been shown to be important in innate immune
      defense, as well as clearance of allergens and apoptotic cells. MMP-9 is a
      protease with a wide variety of substrates, and has been found to be dysregulated
      in a myriad of lung diseases ranging from asthma to cystic fibrosis; in many of
      these conditions, there are decreased levels of SP-D. Our results indicate that
      MMP-9 is able to cleave SP-D in vitro and this cleavage leads to loss of its
      innate immune functions, including its abilities to aggregate bacteria and
      increase phagocytosis by mouse alveolar macrophages. However, MMP-9-cleaved SP-D
      was still detected in a solid-phase E. coli LPS-binding assay, while NE-cleaved
      SP-D was not. In addition, MMP-9 seems to cleave SP-D much more efficiently than
      NE at physiological levels of calcium. Previous studies have shown that in
      several diseases, including cystic fibrosis and asthma, patients have increased
      expression of MMP-9 in the lungs as well as decreased levels of intact SP-D. As
      patients suffering from many of the diseases in which MMP-9 is over-expressed can
      be more susceptible to pulmonary infections, it is possible that MMP-9 cleavage
      of SP-D may contribute to this phenotype.

PMID- 22860024
TI  - Validation of the beta-amy1 transcription profiling assay and selection of
      reference genes suited for a RT-qPCR assay in developing barley caryopsis.
AB  - Reverse transcription coupled with real-time quantitative PCR (RT-qPCR) is a
      frequently used method for gene expression profiling. Reference genes (RGs) are
      commonly employed to normalize gene expression data. A limited information exist
      on the gene expression and profiling in developing barley caryopsis. Expression
      stability was assessed by measuring the cycle threshold (Ct) range and applying
      both the GeNorm (pair-wise comparison of geometric means) and Normfinder (model
      based approach) principles for the calculation. Here, we have identified a set of
      four RGs suitable for studying gene expression in the developing barley
      caryopsis. These encode the proteins GAPDH, HSP90, HSP70 and ubiquitin. We found
      a correlation between the frequency of occurrence of a transcript in silico and
      its suitability as an RG. This set of RGs was tested by comparing the normalized
      level of beta-amylase (beta-amy1) transcript with directly measured quantities of
      the BMY1 gene product in the developing barley caryopsis. This panel of genes
      could be used for other gene expression studies, as well as to optimize beta-amy1
      analysis for study of the impact of beta-amy1 expression upon barley end-use
      quality.

PMID- 22860025
TI  - Association between cardiac autonomic function, oxidative stress and inflammatory
      response in impaired fasting glucose subjects: cross-sectional study.
AB  - BACKGROUND: The worldwide burden of diabetes in 2030 is projected around 552
      million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered
      cardiac autonomic function (CAF) measured by heart rate variability (HRV) is
      observed in early stages of diabetes but the relationship between impaired
      fasting glucose (IFG) and HRV is still debatable. The aim of the study was to
      evaluate the association between CAF, oxidative stress, insulin resistance (IR),
      and inflammatory response in IFG subjects. SUBJECTS AND METHODS: Cross-sectional
      blinded study. Volunteers recruited from health awareness camps underwent CAF and
      biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123)
      were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47).
      The comparison of parameters between the groups was carried out using student t
      test and Mann-Whitney U test for parametric and non-parametric data respectively.
      The correlation between the parameters was analyzed by Spearman's rank
      correlation using SPSS 13.0. RESULTS: The resting cardiovagal modulation
      parameters, heart rate response to forced timed breathing, and orthostatic stress
      were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic
      lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high
      sensitive C-reactive protein, and tumor necrosis factor alpha were increased and
      total antioxidant capacity (TAC) was decreased significantly in IFG group but no
      significant alteration was observed in high-density lipoprotein (HDL-c).
      Cardiovagal modulation parameters were negatively correlated with triglycerides,
      FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC.
      CONCLUSION: There is a continuous interplay between the altered CAF,
      hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG
      in which one factor perpetuates another leading to the progression of disease.

PMID- 22860027
TI  - Two different secondary metabolism gene clusters occupied the same ancestral
      locus in fungal dermatophytes of the arthrodermataceae.
AB  - BACKGROUND: Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes)
      colonize keratinized tissue, such as skin, frequently causing superficial mycoses
      in humans and other mammals, reptiles, and birds. Competition with native
      microflora likely underlies the propensity of these dermatophytes to produce a
      diversity of antibiotics and compounds for scavenging iron, which is extremely
      scarce, as well as the presence of an unusually large number of putative
      secondary metabolism gene clusters, most of which contain non-ribosomal peptide
      synthetases (NRPS), in their genomes. To better understand the historical origins
      and diversification of NRPS-containing gene clusters we examined the evolution of
      a variable locus (VL) that exists in one of three alternative conformations among
      the genomes of seven dermatophyte species. RESULTS: The first conformation of the
      VL (termed VLA) contains only 539 base pairs of sequence and lacks protein-coding
      genes, whereas the other two conformations (termed VLB and VLC) span 36 Kb and 27
      Kb and contain 12 and 10 genes, respectively. Interestingly, both VLB and VLC
      appear to contain distinct secondary metabolism gene clusters; VLB contains a
      NRPS gene as well as four porphyrin metabolism genes never found to be physically
      linked in the genomes of 128 other fungal species, whereas VLC also contains a
      NRPS gene as well as several others typically found associated with secondary
      metabolism gene clusters. Phylogenetic evidence suggests that the VL locus was
      present in the ancestor of all seven species achieving its present distribution
      through subsequent differential losses or retentions of specific conformations.
      CONCLUSIONS: We propose that the existence of variable loci, similar to the one
      we studied, in fungal genomes could potentially explain the dramatic differences
      in secondary metabolic diversity between closely related species of filamentous
      fungi, and contribute to host adaptation and the generation of metabolic
      diversity.

PMID- 22860028
TI  - A large-scale study of anxiety and depression in people with Multiple Sclerosis:
      a survey via the web portal of the UK MS Register.
AB  - INTRODUCTION: Studies have found that people with Multiple Sclerosis experience
      relatively high rates of anxiety and depression. Although methodologically
      robust, many of these studies had access to only modest sample sizes (N<200). The
      aims of this study were to use responses gained via the web portal of the UK MS
      Register (N>4000) to: describe the depression and anxiety profiles of people with
      MS; to determine if anxiety and depression are related to age or disease
      duration; and to assess whether the levels of anxiety and depression differ
      between genders and types of MS. METHODS: From its launch in May 2011 to the end
      of December 2011, 7786 adults with MS enrolled to take part in the UK MS Register
      via the web portal. The responses to the Hospital Anxiety and Depression Scale
      (HADS) were collated with basic demographic and descriptive MS data provided at
      registration and the resulting dataset was analysed in SPSS (v.16). RESULTS: The
      mean HADS score among the 4178 respondents was 15.7 (SE 0.117, SD 7.55) with a
      median of 15.0 (IQR 11). Anxiety and depression rates were notably high, with
      over half (54.1%) scoring >= 8 for anxiety and 46.9% scoring >= 8 for depression.
      Women with relapsing-remitting MS were more anxious than men with this type
      (p<0.001), and than women with other types of MS (p = 0.017). Within each gender,
      men and women with secondary progressive MS were more depressed than men or women
      with other types of MS (p<0.001, p<0.001). CONCLUSIONS: This largest known study
      of its kind has shown that anxiety and depression are highly prevalent in people
      with MS, indicating that their mental health needs could be better addressed.
      These findings support service planning and further research to provide the best
      care for people with MS to help alleviate these debilitating conditions.

PMID- 22860026
TI  - Strategy for identifying dendritic cell-processed CD4+ T cell epitopes from the
      HIV gag p24 protein.
AB  - Mass Spectrometry (MS) is becoming a preferred method to identify class I and
      class II peptides presented on major histocompability complexes (MHC) on antigen
      presenting cells (APC). We describe a combined computational and MS approach to
      identify exogenous MHC II peptides presented on mouse spleen dendritic cells
      (DCs). This approach enables rapid, effective screening of a large number of
      possible peptides by a computer-assisted strategy that utilizes the extraordinary
      human ability for pattern recognition. To test the efficacy of the approach, a
      mixture of epitope peptide mimics (mimetopes) from HIV gag p24 sequence were
      added exogenously to Fms-like tyrosine kinase 3 ligand (Flt3L)-mobilized splenic
      DCs. We identified the exogenously added peptide, VDRFYKTLRAEQASQ, and a second
      peptide, DRFYKLTRAEQASQ, derived from the original exogenously added 15-mer
      peptide. Furthermore, we demonstrated that our strategy works efficiently with
      HIV gag p24 protein when delivered, as vaccine protein, to Flt3L expanded mouse
      splenic DCs in vitro through the DEC-205 receptor. We found that the same MHC II
      bound HIV gag p24 peptides, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, were naturally
      processed from anti-DEC-205 HIV gag p24 protein and presented on DCs. The two
      identified VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ MHC II-bound HIV gag p24 peptides
      elicited CD4(+) T-cell mediated responses in vitro. Their presentation by DCs to
      antigen-specific T cells was inhibited by chloroquine (CQ), indicating that
      optimal presentation of these exogenously added peptides required uptake and
      vesicular trafficking in mature DCs. These results support the application of our
      strategy to identify and characterize peptide epitopes derived from vaccine
      proteins processed by DCs and thus has the potential to greatly accelerate DC
      based vaccine development.

PMID- 22860030
TI  - Conventional QT variability measurement vs. template matching techniques:
      comparison of performance using simulated and real ECG.
AB  - Increased beat-to-beat variability in the QT interval (QTV) of ECG has been
      associated with increased risk for sudden cardiac death, but its measurement is
      technically challenging and currently not standardized. The aim of this study was
      to investigate the performance of commonly used beat-to-beat QT interval
      measurement algorithms. Three different methods (conventional, template
      stretching and template time shifting) were subjected to simulated data featuring
      typical ECG recording issues (broadband noise, baseline wander, amplitude
      modulation) and real short-term ECG of patients before and after infusion of
      sotalol, a QT interval prolonging drug. Among the three algorithms, the
      conventional algorithm was most susceptible to noise whereas the template time
      shifting algorithm showed superior overall performance on simulated and real ECG.
      None of the algorithms was able to detect increased beat-to-beat QT interval
      variability after sotalol infusion despite marked prolongation of the average QT
      interval. The QTV estimates of all three algorithms were inversely correlated
      with the amplitude of the T wave. In conclusion, template matching algorithms, in
      particular the time shifting algorithm, are recommended for beat-to-beat
      variability measurement of QT interval in body surface ECG. Recording noise, T
      wave amplitude and the beat-rejection strategy are important factors of QTV
      measurement and require further investigation.

PMID- 22860029
TI  - AGER -429T/C is associated with an increased lung disease severity in cystic
      fibrosis.
AB  - The clinical course of cystic fibrosis (CF) varies between patients bearing
      identical CFTR mutations, suggesting the involvement of modifier genes. We
      assessed the association of lung disease severity with the variant AGER -429 T/C,
      coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF
      Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del
      homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height
      and mortality. AGER -429T/C polymorphism was genotyped and its function was
      evaluated in vitro by measurement of the luciferase activity. AGER -429 minor
      allele (C) was associated with poorer lung function (p = 0.03). In vitro, the
      promoter activity was higher in cells transfected with AGER -429C compared to
      cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER
      seems to be a modifier gene of lung disease severity in CF, and could be an
      interesting biomarker of CF airway inflammation. The functional promoter AGER 
      429C variant is associated with an increased RAGE expression that can lead to an
      increased lung inflammation and a more severe lung disease.

PMID- 22860032
TI  - Characterization of Rad51 from apicomplexan parasite Toxoplasma gondii: an
      implication for inefficient gene targeting.
AB  - Repairing double strand breaks (DSBs) is absolutely essential for the survival of
      obligate intracellular parasite Toxoplasma gondii. Thus, DSB repair mechanisms
      could be excellent targets for chemotherapeutic interventions. Recent genetic and
      bioinformatics analyses confirm the presence of both homologous recombination
      (HR) as well as non homologous end joining (NHEJ) proteins in this lower
      eukaryote. In order to get mechanistic insights into the HR mediated DSB repair
      pathway in this parasite, we have characterized the key protein involved in
      homologous recombination, namely TgRad51, at the biochemical and genetic levels.
      We have purified recombinant TgRad51 protein to 99% homogeneity and have
      characterized it biochemically. The ATP hydrolysis activity of TgRad51 shows a
      higher K(M) and much lower k(cat) compared to bacterial RecA or Rad51 from other
      related protozoan parasites. Taking yeast as a surrogate model system we have
      shown that TgRad51 is less efficient in gene conversion mechanism. Further, we
      have found that TgRad51 mediated gene integration is more prone towards random
      genetic loci rather than targeted locus. We hypothesize that compromised ATPase
      activity of TgRad51 is responsible for inefficient gene targeting and poor gene
      conversion efficiency in this protozoan parasite. With increase in homologous
      flanking regions almost three fold increments in targeted gene integration is
      observed, which is similar to the trend found with ScRad51. Our findings not only
      help us in understanding the reason behind inefficient gene targeting in T.
      gondii but also could be exploited to facilitate high throughput knockout as well
      as epitope tagging of Toxoplasma genes.

PMID- 22860031
TI  - Mycobacterium tuberculosis complex lipid virulence factors preserved in the
      17,000-year-old skeleton of an extinct bison, Bison antiquus.
AB  - Tracing the evolution of ancient diseases depends on the availability and
      accessibility of suitable biomarkers in archaeological specimens. DNA is
      potentially information-rich but it depends on a favourable environment for
      preservation. In the case of the major mycobacterial pathogens, Mycobacterium
      tuberculosis and Mycobacterium leprae, robust lipid biomarkers are established as
      alternatives or complements to DNA analyses. A DNA report, a decade ago,
      suggested that a 17,000-year-old skeleton of extinct Bison antiquus, from Natural
      Trap Cave, Wyoming, was the oldest known case of tuberculosis. In the current
      study, key mycobacterial lipid virulence factor biomarkers were detected in the
      same two samples from this bison. Fluorescence high-performance liquid
      chromatography (HPLC) indicated the presence of mycolic acids of the
      mycobacterial type, but they were degraded and could not be precisely correlated
      with tuberculosis. However, pristine profiles of C(29), C(30) and C(32)
      mycocerosates and C(27) mycolipenates, typical of the Mycobacterium tuberculosis
      complex, were recorded by negative ion chemical ionization gas chromatography
      mass spectrometry of pentafluorobenzyl ester derivatives. These findings were
      supported by the detection of C(34) and C(36) phthiocerols, which are usually
      esterified to the mycocerosates. The existence of Pleistocene tuberculosis in the
      Americas is confirmed and there are many even older animal bones with well
      characterised tuberculous lesions similar to those on the analysed sample. In the
      absence of any evidence of tuberculosis in human skeletons older than 9,000 years
      BP, the hypothesis that this disease evolved as a zoonosis, before transfer to
      humans, is given detailed consideration and discussion.

PMID- 22860033
TI  - Pertussis circulation has increased T-cell immunity during childhood more than a
      second acellular booster vaccination in Dutch children 9 years of age.
AB  - Here we report the first evaluation of T-cell responses upon a second acellular
      pertussis booster vaccination in Dutch children at 9 years of age, 5 years after
      a preschool booster vaccination. Blood samples of children 9 years of age were
      studied longitudinally until 1 year after the second aP booster and compared with
      those after the first aP booster in children 4 and 6 years of age from a cross
      sectional study. After stimulation with pertussis-vaccine antigens, Th1, Th2 and
      Th17 cytokine responses were measured and effector memory cells (CCR7-CD45RA-)
      were characterized by 8-colour FACS analysis. The second aP booster vaccination
      at pre-adolescent age in wP primed individuals did increase pertussis-specific
      Th1 and Th2 cytokine responses. Noticeably, almost all T-cell responses had
      increased with age and were already high before the booster vaccination at 9
      years of age. The enhancement of T-cell immunity during the 5 year following the
      booster at 4 years of age is probably caused by natural boosting due to the a
      high circulation of pertussis. However, the incidence of pertussis is high in
      adolescents and adults who have only received the Dutch wP vaccine during infancy
      and no booster at 4 years of age. Therefore, an aP booster vaccination at
      adolescence or later in these populations might improve long-term immunity
      against pertussis and reduce the transmission to the vulnerable newborns. TRIAL
      REGISTRATION: Controlled-Trials.com ISRCTN64117538.

PMID- 22860035
TI  - Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend
      on damage complexity.
AB  - The recruitment kinetics of double-strand break (DSB) signaling and repair
      proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live
      cell fluorescence microscopy after ion microirradiation. To investigate the
      influence of damage density and complexity on recruitment kinetics, which cannot
      be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon
      ions with high linear energy transfer per ion (LET = 370 keV/um) to create a
      large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV
      protons with low LET (LET = 2.6 keV/um) to create mainly isolated DSBs. Kinetics
      for all three proteins was characterized by a time lag period T(0) after
      irradiation, during which no foci are formed. Subsequently, the proteins
      accumulate into foci with characteristic mean recruitment times tau(1). Mdc1
      accumulates faster (T(0) = 17 +/- 2 s, tau(1) = 98 +/- 11 s) than 53BP1 (T(0) =
      77 +/- 7 s, tau(1) = 310 +/- 60 s) after high LET irradiation. However,
      recruitment of Mdc1 slows down (T(0) = 73 +/- 16 s, tau(1) = 1050 +/- 270 s)
      after low LET irradiation. The recruitment kinetics of Rad52 is slower than that
      of Mdc1, but exhibits the same dependence on LET. In contrast, the mean
      recruitment time tau(1) of 53BP1 remains almost constant when varying LET.
      Comparison to literature data on Mdc1 recruitment after UV laser irradiation
      shows that this rather resembles recruitment after high than low LET ionizing
      radiation. So this work shows that damage quality has a large influence on repair
      processes and has to be considered when comparing different studies.

PMID- 22860034
TI  - Dengue virus infection mediates HMGB1 release from monocytes involving PCAF
      acetylase complex and induces vascular leakage in endothelial cells.
AB  - High mobility group box 1 (HMGB1) protein is released from cells as a pro
      inflammatory cytokine in response to an injury or infection. During dengue
      hemorrhagic fever (DHF)/dengue shock syndrome (DSS), a number of pro-inflammatory
      cytokines are released, contributing to disease pathogenesis. In this study, the
      release of HMGB1 from human myelogenous leukemia cell line K562 and primary
      peripheral blood monocytes (PBM) cells was examined during dengue virus (DV)
      infection. HMGB1 was shown to translocate from cell nuclei to the cytoplasm in
      both K562- and PBM-infected cells. The translocation of HMGB1 from the nucleus to
      the cytoplasm was shown to be mediated by the host cell p300/CBP-associated
      factor (PCAF) acetylase complex in K562 cells. In addition, DV capsid protein was
      observed to be the putative viral protein in actuating HMGB1 migration from the
      nucleus to cytoplasm through the involvement of PCAF acetylase. HMGB1 was
      released from DV-infected K562 cells into the extracellular milieu in a
      multiplicity of infection (M.O.I.)-independent manner and its release can be
      inhibited by the addition of 1-5 mM of ethyl pyruvate (EP) in a dose-dependent
      manner. Application of DV-infected K562 cell culture supernatants to primary
      endothelial cells induced vascular permeability. In contrast, supernatants from
      DV-infected K562 cells treated with EP or HMGB1 neutralizing antibody were
      observed to maintain the structural integrity of the vascular barrier.

PMID- 22860036
TI  - Development of a charting method to monitor the individual performance of
      surgeons at the beginning of their career.
AB  - BACKGROUND: Efforts to provide a valid picture of surgeons' individual
      performance evolution should frame their outcomes in relation to what is expected
      depending on their experience. We derived the learning curve of young
      thyroidectomy surgeons as a baseline to enable the accurate assessment of their
      individual outcomes and avoid erroneous conclusions that may derive from more
      traditional approaches. METHODS: Operative time and postoperative recurrent
      laryngeal nerve palsy of 2006 patients who underwent a thyroidectomy performed by
      19 young surgeons in five academic hospitals were monitored from April 2008 to
      December 2009. The database was randomly divided into training and testing
      datasets. The training data served to determine the expected performance curve of
      surgeons during their career and factors influencing outcome variation using
      generalized estimating equations (GEEs). To simulate prospective monitoring of
      individual surgeon outcomes, the testing data were plotted on funnel plots and
      cumulative sum charts (CUSUM). Performance charting methods were utilized to
      present outcomes adjusted both for patient case-mix and surgeon experience.
      RESULTS: Generation of performance curves demonstrated a gradual reduction in
      operative time from 139 (95% CI, 137 to 141) to 75 (71 to 80) minutes, and from
      15.7% (15.1% to 16.3%) to 3.3% (3.0% to 3.6%) regarding the nerve palsy rate.
      Charts interpretation revealed that a very young surgeon had better outcomes than
      expected, whereas a more experienced surgeon appeared to be a poor performer
      given the number of years that he had already spent in practice. CONCLUSIONS: Not
      considering the initial learning curve of surgeons exposes them to biased
      measurement and to misinterpretation in assessing their individual performance
      for thyroidectomy. The performance chart represents a valuable tool to monitor
      the outcome of surgeons with the expectation to provide safe and efficient care
      to patients.

PMID- 22860037
TI  - Staurosporine induces necroptotic cell death under caspase-compromised conditions
      in U937 cells.
AB  - For a long time necrosis was thought to be an uncontrolled process but evidences
      recently have revealed that necrosis can also occur in a regulated manner.
      Necroptosis, a type of programmed necrosis is defined as a death receptor
      initiated process under caspase-compromised conditions. The process requires the
      kinase activity of receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3)
      and mixed lineage kinase domain-like protein (MLKL), as a substrate of RIPK3. The
      further downstream events remain elusive. We applied known inhibitors to
      characterize the contributing enzymes in necroptosis and their effect on cell
      viability and different cellular functions were detected mainly by flow
      cytometry. Here we report that staurosporine, the classical inducer of intrinsic
      apoptotic pathway can induce necroptosis under caspase-compromised conditions in
      U937 cell line. This process could be hampered at least partially by the RIPK1
      inhibitor necrotstin-1 and by the heat shock protein 90 kDa inhibitor
      geldanamycin. Moreover both the staurosporine-triggered and the classical death
      ligand-induced necroptotic pathway can be effectively arrested by a lysosomal
      enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor
      necrosulfonamide. We also confirmed that the enzymatic role of poly(ADP
      ribose)polymerase (PARP) is dispensable in necroptosis but it contributes to
      membrane disruption in secondary necrosis. In conclusion, we identified a novel
      way of necroptosis induction that can facilitate our understanding of the
      molecular mechanisms of necroptosis. Our results shed light on alternative
      application of staurosporine, as a possible anticancer therapeutic agent.
      Furthermore, we showed that the CA-074-OMe has a target in the signaling pathway
      leading to necroptosis. Finally, we could differentiate necroptotic and secondary
      necrotic processes based on participation of PARP enzyme.

PMID- 22860038
TI  - Small molecule-assisted, line-independent maintenance of human pluripotent stem
      cells in defined conditions.
AB  - Human pluripotent stem cells (hPSCs) are conventionally grown in a mouse feeder
      cell-dependent manner. Chemically defined culture conditions are, however,
      desirable not only for potential medically oriented applications but also for
      investigating mechanisms of self-renewal and differentiation. In light of the
      rather high complexity and cost of existing defined hPSC culture systems, we have
      systematically evaluated over 20 potential media ingredients. Only components
      that reproducibly gave beneficial effects were ultimately combined to yield a
      simple and cost-effective formulation termed FTDA. This xeno-free medium is based
      on mimicking self-renewal factor activities present in mouse embryonic fibroblast
      conditioned medium, at minimal dosages. Additionally, small molecule inhibitors
      of BMP and WNT signaling served to specifically suppress typical types of
      spontaneous differentiation seen in hPSC cultures. FTDA medium was suitable for
      the generation of human induced pluripotent stem cells and enabled robust long
      term maintenance of diverse hPSC lines including hard-to-grow ones. Comparisons
      with existing defined media suggested reduced spontaneous differentiation rates
      in FTDA. Our results imply that using supportive factors at minimal
      concentrations may still promote robust self-renewal and preserve pluripotency of
      hPSCs.

PMID- 22860039
TI  - Prion protein and Shadoo are involved in overlapping embryonic pathways and
      trophoblastic development.
AB  - The potential requirement of either the Prion or Shadoo protein for early mouse
      embryogenesis was recently suggested. However, the current data did not allow to
      precise the developmental process that was affected in the absence of both
      proteins and that led to the observed early lethal phenotype. In the present
      study, using various Prnp transgenic mouse lines and lentiviral vectors
      expressing shRNAs that target the Shadoo-encoding mRNA, we further demonstrate
      the specific requirement of at least one of these two PrP-related proteins at
      early developmental stages. Histological analysis reveals developmental defect of
      the ectoplacental cone and important hemorrhage surrounding the Prnp-knockout
      Sprn-knockdown E7.5 embryos. By restricting the RNA interference to the
      trophoblastic cell lineages, the observed lethal phenotype could be attributed to
      the sole role of these proteins in this trophectoderm-derived compartment. RNAseq
      analysis performed on early embryos of various Prnp and Sprn genotypes indicated
      that the simultaneous down-regulation of these two proteins affects cell-adhesion
      and inflammatory pathways as well as the expression of ectoplacental-specific
      genes. Overall, our data provide biological clues in favor of a crucial and
      complementary embryonic role of the prion protein family in Eutherians and
      emphasizes the need to further evaluate its implication in normal and
      pathological human placenta biology.

PMID- 22860040
TI  - Selective cytotoxicity of amidinopiperidine based compounds towards Burkitt's
      lymphoma cells involves proteasome inhibition.
AB  - Serine proteases have proven to be promising pharmacological targets in
      contemporary drug discovery for cancer treatment. Since azaphenylalanine-based
      compounds manifest cytotoxic activity, we have selected serine protease
      inhibitors designed and synthesized in-house with large hydrophobic naphthalene
      moiety for screening. The cytotoxic potential of screened molecules was
      correlated to modifications of R(1) residues. The most cytotoxic were compounds
      with greater basicity; amidinopiperidines, piperidines and benzamidines.
      Amidinopiperidine-based compounds exert cytotoxicity in low uM range, with IC(50)
      18 uM and 22 uM for inhibitors 15 and 16 respectively. These compounds exhibited
      selective cytotoxicity towards the Burkitt's lymphoma cells Ramos and Daudi, and
      proved nontoxic to PMBC, Jurkat and U937. They induce caspase-dependent apoptotic
      cell death, as demonstrated by the use of a pan-caspase inihibitor, zVADfmk,
      which was able to rescue Ramos cells from compound(s)-induced apoptosis. We
      confirm a disruption of the pro-survival pathway in Burkitt's lymphoma through
      NFkappaB inhibition. The accumulation of phosphorylated precursor (p105) and
      inhibitory (IkappaB) molecules with no subsequent release of active NFkappaB
      implicated the involvement of proteasome. Indeed, we show that the
      amidinopiperidine-based compounds inhibit all three proteolytical activities of
      the human 20S proteasome, with the most prominent effect being on the trypsin
      like activity. Consistently, treatment of Ramos cells with these compounds led to
      an increase in ubiquitinated proteins. The amidinopiperidine-based serine
      protease inhibitors presented are, as selective inducers of apoptosis in
      Burkitt's lymphoma cells, promising leads for the development of novel
      chemotherapeutics.

PMID- 22860041
TI  - Unveiling trophic functions of uncultured protist taxa by incubation experiments
      in the brackish Baltic Sea.
AB  - BACKGROUND: Our knowledge of the phylogeny and diversity of aquatic protists is
      rapidly increasing due to molecular surveys and next-generation sequencing
      approaches. This has led to a considerable discrepancy between the taxa known
      from cultures and those known from environmental 18S rRNA gene sequences. Hence,
      it is generally difficult to assign ecological functions to new taxa detected by
      culture-independent molecular approaches. METHODOLOGY/PRINCIPAL FINDINGS: A
      combination of unamended dark incubations and 18S rRNA sequencing was chosen to
      link molecular diversity data of uncultured protists with heterotrophic,
      presumably bacterivorous, growth. The incubations, conducted with Baltic Sea
      brackish water, resulted in a consistent shift from a protistan community
      dominated by phototrophs to one in which heterotrophs predominated. This was
      determined on the basis of cell abundance and 18S rRNA sequences derived from
      fingerprint analysis and clone libraries. The bulk of enriched phylotypes after
      incubation were related to hitherto uncultured marine taxa within chrysophytes,
      ochrophytes, choanoflagellates, cercozoans, and picobiliphytes, mostly
      represented in recently established or here defined environmental clades. Their
      growth in the dark, together with coinciding results from studies with a similar
      objective, provides evidence that these uncultured taxa represent heterotrophic
      or mixotrophic species. CONCLUSIONS/SIGNIFICANCE: These findings shed some light
      into the trophic role of diverse uncultured protists especially within
      functionally heterogeneous groups (e.g., chrysophytes, ochrophytes) and groups
      that appear to be puzzling with regard to their nutrition (picobiliphytes).
      Additionally, our results indicate that the heterotrophic flagellate community in
      the southwestern Baltic Sea is dominated by species of marine origin. The
      combination of unamended incubations with molecular diversity analysis is thus
      confirmed as a promising approach to explore the trophic mode of environmentally
      relevant protist taxa for which only sequence data are currently available.

PMID- 22860042
TI  - In hypertrophic cardiomyopathy reduction of relative resting myocardial blood
      flow is related to late enhancement, T2-signal and LV wall thickness.
AB  - OBJECTIVES: To quantify resting myocardial blood flow (MBF) in the left
      ventricular (LV) wall of HCM patients and to determine the relationship to
      important parameters of disease: LV wall thickness, late gadolinium enhancement
      (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract
      obstruction and age. MATERIALS AND METHODS: Seventy patients with proven HCM
      underwent cardiac MRI. Absolute and relative resting MBF were calculated from
      cardiac perfusion MRI by using the Fermi function model. The relationship between
      relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2
      bright signal), LGE, age and LV outflow gradient as determined by
      echocardiography was determined using simple and multiple linear regression
      analysis. Categories of reduced and elevated perfusion in relation to non- or
      mildly affected reference segments were defined, and T2-signal characteristics
      and extent as well as pattern of LGE were examined. Statistical testing included
      linear and logistic regression analysis, unpaired t-test, odds ratios, and
      Fisher's exact test. RESULTS: 804 segments in 70 patients were included in the
      analysis. In a simple linear regression model LV wall thickness (p<0.001), extent
      of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001),
      T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative
      resting MBF. The LV outflow gradient did not show any effect on resting perfusion
      (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001),
      edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of
      relative resting MBF. Segments with reduced resting perfusion demonstrated
      different LGE patterns compared to segments with elevated resting perfusion.
      CONCLUSION: In HCM resting MBF is significantly reduced depending on LV wall
      thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore,
      different patterns of perfusion in HCM patients have been defined, which may
      represent different stages of disease.

PMID- 22860043
TI  - High risk of ART non-adherence and delay of ART initiation among HIV positive
      double orphans in Kigali, Rwanda.
AB  - BACKGROUND: To reduce HIV/AIDS related mortality of children, adherence to
      antiretroviral treatment (ART) is critical in the treatment of HIV positive
      children. However, little is known about the association between ART adherence
      and different orphan status. The aims of this study were to assess the ART
      adherence and identify whether different orphan status was associated with the
      child's adherence. METHODS: A total of 717 HIV positive children and the same
      number of caregivers participated in this cross-sectional study. Children's
      adherence rate was measured using a pill count method and those who took 85% or
      more of the prescribed doses were defined as adherent. To collect data about
      adherence related factors, we also interviewed caregivers using a structured
      questionnaire. RESULTS: Of all children (N = 717), participants from each orphan
      category (double orphan, maternal orphan, paternal orphan, non-orphan) were 346,
      89, 169, and 113, respectively. ART non-adherence rate of each orphan category
      was 59.3%, 44.9%, 46.7%, and 49.7%, respectively. The multivariate analysis
      indicated that maternal orphans (AOR 0.31, 95% CI 0.12-0.80), paternal orphans
      (AOR 0.35, 95% CI 0.14-0.89), and non-orphans (AOR 0.45, 95% CI 0.21-0.99) were
      less likely to be non-adherent compared to double orphans. Double orphans who had
      a sibling as a caregiver were more likely to be non-adherent. The first mean CD4
      count prior to initiating treatment was 520, 601, 599, and 844 (cells/ml),
      respectively (p<0.001). Their mean age at sero-status detection was 5.9, 5.3,
      4.8, and 3.9 (year old), respectively (p<0.001). CONCLUSIONS: Double orphans were
      at highest risk of ART non-adherence and especially those who had a sibling as a
      caregiver had high risk. They were also in danger of initiating ART at an older
      age and at a later stage of HIV/AIDS compared with other orphan categories.
      Double orphans need more attention to the promote child's adherence to ART.

PMID- 22860044
TI  - Functional subdivision of group-ICA results of fMRI data collected during cinema
      viewing.
AB  - Independent component analysis (ICA) can unravel functional brain networks from
      functional magnetic resonance imaging (fMRI) data. The number of the estimated
      components affects both the spatial pattern of the identified networks and their
      time-course estimates. Here group-ICA was applied at four dimensionalities (10,
      20, 40, and 58 components) to fMRI data collected from 15 subjects who viewed a
      15-min silent film ("At land" by Maya Deren). We focused on the dorsal attention
      network, the default-mode network, and the sensorimotor network. The lowest
      dimensionalities demonstrated most prominent activity within the dorsal attention
      network, combined with the visual areas, and in the default-mode network; the
      sensorimotor network only appeared with ICA comprising at least 20 components.
      The results suggest that even very low-dimensional ICA can unravel the most
      prominent functionally-connected brain networks. However, increasing the number
      of components gives a more detailed picture and functionally feasible subdivision
      of the major networks. These results improve our understanding of the
      hierarchical subdivision of brain networks during viewing of a movie that
      provides continuous stimulation embedded in an attention-directing narrative.

PMID- 22860045
TI  - A comprehensive characterization of genome-wide copy number aberrations in
      colorectal cancer reveals novel oncogenes and patterns of alterations.
AB  - To develop a comprehensive overview of copy number aberrations (CNAs) in stage
      II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3
      clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal
      common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.8%), 8 q (33.1%)
      and 13 q (51.0%) and losses on 18 (58.6%), 4 q (26%) and 21 q (21.6%). MSS tumors
      have significantly more CNAs than microsatellite-instable (MSI) tumors: within
      the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was
      identified (p<0.01). Focal aberrations identified by the GISTIC method confirmed
      amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and
      deletions of tumor suppressors including TP53, APC, and SMAD4, and gene
      expression was highly concordant with copy number aberration for these genes.
      Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also
      showed high concordance between copy number and expression. Survival analysis
      associated a specific patient segment featured by chromosome 20 q gains to an
      improved overall survival, which might be due to higher expression of genes such
      as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a
      poor prognosis BRAF-mutant-like signature derived from mRNA data from this
      cohort. We further revealed non-random correlation between CNAs among unlinked
      loci, including positive correlation between 20 q gain and 8 q gain, and 20 q
      gain and chromosome 18 loss, consistent with co-selection of these CNAs. These
      results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and
      highlight loci and genes that may play an important role in driving the
      development and outcome of this disease.

PMID- 22860046
TI  - Cathepsin K-Cre causes unexpected germline deletion of genes in mice.
AB  - Osteoclasts are terminally differentiated cells that attach to bone and secrete
      proteases to degrade the bone matrix. The primary protease responsible for the
      degradation of the organic component of the bone matrix is Cathepsin K, which was
      largely thought to be unique to osteoclasts. Given its apparent selective
      expression in osteoclasts, the Cathepsin K promoter has been engineered to drive
      the expression of Cre recombinase in mice and has been the most relevant tool for
      generating osteoclast-specific gene loss. In an effort to understand the role of
      the ARF tumor suppressor in osteoclasts, we crossed Arf (fl/fl) mice to
      Ctsk(Cre/+) mice, which unexpectedly resulted in the germline loss of Arf. We
      subsequently confirmed Cre activity in gametes by generating Ctsk(Cre/+); Rosa(+)
      mice. These results raise significant concerns regarding in vivo bone phenotypes
      created using Ctsk(Cre/+) mice and warrant further investigation into the role of
      Cathepsin K in gametes as well as alternative tools for studying osteoclast
      specific gene loss in vivo.

PMID- 22860047
TI  - The dynamics of condom use with regular and casual partners: analysis of the 2006
      National Sexual Behavior Survey of Thailand.
AB  - OBJECTIVE: This study aims to determine factors associated with levels of condom
      use among heterosexual Thai males in sex with regular partners and in sex with
      casual partners. METHODS: The data used in this study are from the national
      probability sample of the 2006 National Sexual Behavior Study, the third
      nationally representative cross-sectional survey in Thailand. A subtotal of 2,281
      men were analyzed in the study, including young (18-24) and older (25-59) adults
      who were residents of rural areas of Thailand, non-Bangkok urban areas, and
      Bangkok. Two outcomes of interest for this analysis are reported condom use in
      the past 12 months by males in relationships with the most recent regular and
      casual partners who were not sex workers. Chi-square statistics, bivariate
      regressions and the proportional odds regression models are used in the analysis.
      RESULTS: Condom use for men with their regular partner is revealed to be
      positively related to education, knowledge of condom effectiveness, and pro
      condom strategy, and negatively related to non-professional employment, status of
      registered marriage, and short relationship duration. Condom use with casual
      partner is positively determined by education, condom knowledge, non-professional
      occupation, short relationship duration, and lack of history of paid sex.
      CONCLUSION: The national survey emphasized the importance of risk perceptions and
      condom motivations variables in explaining condom use among men in Thailand.
      These factors include not only education and knowledge of condom effectiveness
      and pro-condom strategy but also types of partners and their relationship context
      and characteristics. Program intervention to promote condom use in Thailand in
      this new era of predominant casual sex rather than sex with sex workers has to
      take into account more dynamic partner-based strategies than in the past history
      of the epidemics in Thailand.

PMID- 22860048
TI  - Robustness and information propagation in attractors of Random Boolean Networks.
AB  - Attractors represent the long-term behaviors of Random Boolean Networks. We study
      how the amount of information propagated between the nodes when on an attractor,
      as quantified by the average pairwise mutual information (I(A)), relates to the
      robustness of the attractor to perturbations (R(A)). We find that the dynamical
      regime of the network affects the relationship between I(A) and R(A). In the
      ordered and chaotic regimes, I(A) is anti-correlated with R(A), implying that
      attractors that are highly robust to perturbations have necessarily limited
      information propagation. Between order and chaos (for so-called "critical"
      networks) these quantities are uncorrelated. Finite size effects cause this
      behavior to be visible for a range of networks, from having a sensitivity of 1 to
      the point where I(A) is maximized. In this region, the two quantities are weakly
      correlated and attractors can be almost arbitrarily robust to perturbations
      without restricting the propagation of information in the network.

PMID- 22860049
TI  - Impact of leucocyte depletion and prion reduction filters on TSE blood borne
      transmission.
AB  - The identification in the UK of 4 v-CJD infected patients thought to be due to
      the use of transfused Red Blood Cell units prepared from blood of donors
      incubating v-CJD raised major concerns in transfusion medicine. The demonstration
      of leucocyte associated infectivity using various animal models of TSE infection
      led to the implementation of systematic leuco-depletion (LD) of Red Blood cells
      concentrates (RBCs) in a number of countries. In the same models, plasma also
      demonstrated a significant level of infectivity which raised questions on the
      impact of LD on the v-CJD transmission risk. The recent development of filters
      combining LD and the capture of non-leucocyte associated prion infectivity meant
      a comparison of the benefits of LD alone versus LD/prion-reduction filters
      (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of
      blood/plasma volumes to human transfusion medicine an experimental TSE sheep
      model was used to characterize the abilities of whole blood, RBCs, plasma and
      buffy-coat to transmit the disease through the transfusion route. The impact of a
      standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the
      disease transmission was then measured. Homologous recipients transfused with
      whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency.
      Conversely, plasma, when intravenously administered resulted in an inconstant
      infection of the recipients and no disease transmission was observed in sheep
      that received cryo-precipitated fraction or supernatant obtained from infectious
      plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood
      Cells concentrate did not provide absolute protection from infection. These
      results support the view that leuco-depletion strongly mitigates the v-CJD blood
      borne transmission risk and provide information about the relative benefits of
      prion reduction filters.

PMID- 22860050
TI  - Regulation of nuclear factor kappaB (NF-kappaB) transcriptional activity via p65
      acetylation by the chaperonin containing TCP1 (CCT).
AB  - The NF-kappaB family member p65 is central to inflammation and immunity. The
      purpose of this study was to identify and characterize evolutionary conserved
      genes modulating p65 transcriptional activity. Using an RNAi screening approach,
      we identified chaperonin containing TCP1 subunit eta (CCTeta) as a regulator of
      Drosophila NF-kappaB proteins, Dorsal and Dorsal-related immunity factor (Dif).
      CCTeta was also found to regulate NF-kappaB-driven transcription in mammalian
      cells, acting in a promoter-specific context, downstream of IkappaB kinase (IKK).
      CCTeta knockdown repressed IkappaBalpha and CXCL2/MIP2 transcription during the
      early phase of NF-kappaB activation while impairing the termination of
      CCL5/RANTES and CXCL10/IP10 transcription. The latter effect was associated with
      increased DNA binding and reduced p65 acetylation, presumably by altering the
      activity of histone acetyltransferase CREB-binding protein (CBP). We identified
      p65 lysines (K) 122 and 123 as target residues mediating the CCTeta-driven
      termination of NF-kappaB-dependent transcription. We propose that CCTeta
      regulates NF-kappaB activity in a manner that resolves inflammation.

PMID- 22860051
TI  - Humanized c-Myc mouse.
AB  - BACKGROUND: A given tumor is usually dependent on the oncogene that is activated
      in the respective tumor entity. This phenomenon called oncogene addiction
      provides the rationale for attempts to target oncogene products in a therapeutic
      manner, be it by small molecules, by small interfering RNAs (siRNA) or by antigen
      specific T cells. As the proto-oncogene product is required also for the function
      of normal cells, this raises the question whether there is a therapeutic window
      between the adverse effects of specific inhibitors or T cells to normal tissue
      that may limit their application, and their beneficial tumor-specific therapeutic
      action. To address this crucial question, suitable mouse strains need to be
      developed, that enable expression of the human proto-oncogene not only in tumor
      but also in normal cells. The aim of this work is to provide such a mouse strain
      for the human proto-oncogene product c-MYC. PRINCIPAL FINDINGS: We generated
      C57BL/6-derived embryonic stem cells that are transgenic for a humanized c-Myc
      gene and established a mouse strain (hc-Myc) that expresses human c-MYC instead
      of the murine ortholog. These transgenic animals harbor the humanized c-Myc gene
      integrated into the endogenous murine c-Myc locus. Despite the lack of the
      endogenous murine c-Myc gene, homozygous mice show a normal phenotype indicating
      that human c-MYC can replace its murine ortholog. CONCLUSIONS: The newly
      established hc-Myc mouse strain provides a model system to study in detail the
      adverse effects of therapies that target the human c-MYC protein. To mimic the
      clinical situation, hc-Myc mice may be cross-bred to mice that develop tumors due
      to overexpression of human c-MYC. With these double transgenic mice it will be
      possible to study simultaneously the therapeutic efficiency and adverse side
      effects of MYC-specific therapies in the same mouse.

PMID- 22860052
TI  - Local arginase inhibition during early reperfusion mediates cardioprotection via
      increased nitric oxide production.
AB  - Consumption of L-arginine contributes to reduced bioavailability of nitric oxide
      (NO) that is critical for the development of ischemia-reperfusion injury. The aim
      of the study was to determine myocardial arginase expression and activity in
      ischemic-reperfusion myocardium and whether local inhibition of arginase within
      the ischemic myocardium results in increased NO production and protection against
      myocardial ischemia-reperfusion. Anesthetized pigs were subjected to coronary
      artery occlusion for 40 min followed by 4 h reperfusion. The pigs were randomized
      to intracoronary infusion of vehicle (n = 7), the arginase inhibitor N-hydroxy
      nor-L-arginine (nor-NOHA, 2 mg/min, n = 7), the combination of nor-NOHA and the
      NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 0.35 mg/min, n = 6)
      into the jeopardized myocardial area or systemic intravenous infusion of nor-NOHA
      (2 mg/min, n = 5) at the end of ischemia and start of reperfusion. The infarct
      size of the vehicle group was 80 +/- 4% of the area at risk. Intracoronary nor
      NOHA reduced infarct size to 46 +/- 5% (P<0.01). Co-administration of L-NMMA
      abrogated the cardioprotective effect mediated by nor-NOHA (infarct size 72 +/-
      6%). Intravenous nor-NOHA did not reduce infarct size. Arginase I and II were
      expressed in cardiomyocytes, endothelial, smooth muscle and poylmorphonuclear
      cells. There was no difference in cytosolic arginase I or mitochondrial arginase
      II expression between ischemic-reperfused and non-ischemic myocardium. Arginase
      activity increased 2-fold in the ischemic-reperfused myocardium in comparison
      with non-ischemic myocardium. In conclusion, ischemia-reperfusion increases
      arginase activity without affecting cytosolic arginase I or mitochondrial
      arginase II expression. Local arginase inhibition during early reperfusion
      reduces infarct size via a mechanism that is dependent on increased
      bioavailability of NO.

PMID- 22860053
TI  - Drivers and spatio-temporal extent of hyporheic patch variation: implications for
      sampling.
AB  - The hyporheic zone in stream ecosystems is a heterogeneous key habitat for
      species across many taxa. Consequently, it attracts high attention among
      freshwater scientists, but generally applicable guidelines on sampling strategies
      are lacking. Thus, the objective of this study was to develop and validate such
      sampling guidelines. Applying geostatistical analysis, we quantified the spatio
      temporal variability of parameters, which characterize the physico-chemical
      substratum conditions in the hyporheic zone. We investigated eight stream reaches
      in six small streams that are typical for the majority of temperate areas. Data
      was collected on two occasions in six stream reaches (development data), and once
      in two additional reaches, after one year (validation data). In this study, the
      term spatial variability refers to patch contrast (patch to patch variance) and
      patch size (spatial extent of a patch). Patch contrast of hyporheic parameters
      (specific conductance, pH and dissolved oxygen) increased with macrophyte cover
      (r(2)=0.95, p<0.001), while patch size of hyporheic parameters decreased from 6
      to 2 m with increasing sinuosity of the stream course (r(2)=0.91, p<0.001),
      irrespective of the time of year. Since the spatial variability of hyporheic
      parameters varied between stream reaches, our results suggest that sampling
      design should be adapted to suit specific stream reaches. The distance between
      sampling sites should be inversely related to the sinuosity, while the number of
      samples should be related to macrophyte cover.

PMID- 22860054
TI  - CD4+CD25+ regulatory T cell depletion modulates anxiety and depression-like
      behaviors in mice.
AB  - Stress has been shown to suppress immune function and increase susceptibility to
      inflammatory disease and psychiatric disease. CD4(+)CD25(+) regulatory T (Treg)
      cells are prominent in immune regulation. This study was conducted to determine
      if anti-CD25 antibody (Ab) mediated depletion of Treg cells in mice
      susceptibility to stress-induced development of depression-like behaviors, as
      well as immunological and neurochemical activity. To accomplish this, an elevated
      plus-maze test (EPM), tail suspension test (TST), and forced swim test (FST) were
      used to examine depression-like behaviors upon chronic immobilization stress.
      Immune imbalance status was observed based on analysis of serum cytokines using a
      mouse cytometric bead array in conjunction with flow cytometry and changes in the
      levels of serotonin (5-HT) and dopamine (DA) in the brain were measured by high
      performance liquid chromatography (HPLC). The time spent in the open arms of the
      EPM decreased significantly and the immobility time in the FST increased
      significantly in the anti-CD25 Ab-treated group when compared with the non
      stressed wild-type group. In addition, interlukin-6 (IL-6), tumor necrosis factor
      a (TNF-a), interlukin-2 (IL-2), interferon-gamma (IFN-gamma), interlukin-4 (IL-4)
      and interlukin-17A (IL-17A) concentrations were significantly upregulated in the
      stressed anti-CD25 Ab-treated group when compared with the non stressed wild-type
      group. Furthermore, the non stressed anti-CD25 Ab-treated group displayed
      decreased 5-HT levels within the hippocampus when compared with the non stressed
      wild-type group. These results suggest that CD4(+)CD25(+) Treg cell depletion
      modulated alterations in depressive behavior, cytokine and monoaminergic
      activity. Therefore, controlling CD4(+)CD25(+) Treg cell function during stress
      may be a potent therapeutic strategy for the treatment of depression-like
      symptoms.

PMID- 22860055
TI  - Proteomic analysis of PKCgamma-related proteins in the spinal cord of morphine
      tolerant rats.
AB  - BACKGROUND: Morphine tolerance is a common drawback of chronic morphine exposure,
      hindering use of this drug. Studies have shown that PKCa may play a key role in
      the development of morphine tolerance, although the mechanisms are not fully
      known. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of morphine tolerance, PKCa
      knockdown in the spinal cord was successfully carried out using RNA interference
      (RNAi) with lentiviral vector-mediated short hairpin RNA of PKCa (LV-shPKCa).
      Spinal cords (L4-L5) were obtained surgically from morphine-tolerant (MT) rats
      with and without PKCa knockdown, for comparative proteomic analysis. Total
      proteins from the spinal cords (L4-L5) were extracted and separated using two
      dimensional gel electrophoresis (2DGE); 2D gel images were analyzed with PDQuest
      software. Seven differential gel-spots were observed with increased spot volume,
      and 18 spots observed with decreased spot volume. Among these, 13 differentially
      expressed proteins (DEPs) were identified with matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), comparing
      between MT rats with and without PKCa knockdown. The DEPs identified have roles
      in the cytoskeleton, as neurotrophic factors, in oxidative stress, in ion
      metabolism, in cell signaling, and as chaperones. Three DEPs (GFAP, FSCN and
      GDNF) were validated with Western blot analysis, confirming the DEP data.
      Furthermore, using immunohistochemical analysis, we reveal for the first time
      that FSCN is involved in the development of morphine tolerance.
      CONCLUSIONS/SIGNIFICANCE: These data cast light on the proteins associated with
      the PKCa activity during morphine tolerance, and hence may contribute to
      clarification of the mechanisms by which PKCa influences MT.

PMID- 22860056
TI  - Efficient amplification of chimeric adenovirus 5/40S vectors carrying the short
      fiber protein of Ad40 in suspension cell cultures.
AB  - The human adenovirus 40 (Ad40) is a promising tool for gene therapy of intestinal
      diseases. Since the production of Ad40 in vitro is extremely inefficient,
      chimeric Adenovirus 5/40S vectors carrying the Ad40 short fiber on the Ad5 capsid
      have been developed. However, Ad5/40S productivity is low. We hypothesized that
      low productivity was a result of inefficient viral entry into producer cells
      during amplification. To this end, we have developed a production strategy based
      on using 211B cells (expressing Ad5 fiber) during amplification steps, while
      Ad5/40S infectivity is further improved by adding polybrene during infections. In
      addition, the optimal harvesting time was determined by evaluating the Ad5/40S
      viral cycle. The developed production strategy significantly reduces the number
      of amplification cycles and duration of the process. Finally, to further
      facilitate Ad5/40S production, 211B cells were adapted to suspension thus
      allowing to easily upscale the production process in bioreactors.

PMID- 22860057
TI  - RhoA GTPase switch controls Cx43-hemichannel activity through the contractile
      system.
AB  - ATP-dependent paracrine signaling, mediated via the release of ATP through plasma
      membrane-embedded hemichannels of the connexin family, coordinates a synchronized
      response between neighboring cells. Connexin 43 (Cx43) hemichannels that are
      present in the plasma membrane need to be tightly regulated to ensure cell
      viability. In monolayers of bovine corneal endothelial cells (BCEC),Cx43-mediated
      ATP release is strongly inhibited when the cells are treated with inflammatory
      mediators, in particular thrombin and histamine. In this study we investigated
      the involvement of RhoA activation in the inhibition of hemichannel-mediated ATP
      release in BCEC. We found that RhoA activation occurs rapidly and transiently
      upon thrombin treatment of BCEC. The RhoA activity correlated with the onset of
      actomyosin contractility that is involved in the inhibition of Cx43 hemichannels.
      RhoA activation and inhibition of Cx43-hemichannel activity were both prevented
      by pre-treatment of the cells with C3-toxin as well as knock down of RhoA by
      siRNA. These findings provide evidence that RhoA activation is a key player in
      thrombin-induced inhibition of Cx43-hemichannel activity. This study demonstrates
      that RhoA GTPase activity is involved in the acute inhibition of ATP-dependent
      paracrine signaling, mediated by Cx43 hemichannels, in response to the
      inflammatory mediator thrombin. Therefore, RhoA appears to be an important
      molecular switch that controls Cx43 hemichannel openings and hemichannel-mediated
      ATP-dependent paracrine intercellular communication under (patho)physiological
      conditions of stress.

PMID- 22860058
TI  - Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery
      from sickness behaviour in mice.
AB  - Molecular hydrogen has been shown to have neuroprotective effects in mouse models
      of acute neurodegeneration. The effect was suggested to be mediated by its free
      radical scavenger properties. However, it has been shown recently that molecular
      hydrogen alters gene expression and protein phosphorylation. The aim of this
      study was to test whether chronic ad libitum consumption of molecular hydrogen
      enriched electrochemically reduced water (H-ERW) improves the outcome of
      lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the
      initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS
      (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness
      behaviour was assessed 2 h after the injection, and recovery was assessed by
      monitoring the spontaneous locomotor activity in the homecage for 72 h after the
      administration of LPS. The mice were killed in the acute or recovery phase, and
      the expression of pro- and antiinflammatory cytokines in the hippocampus was
      assessed by real-time PCR. We found that molecular hydrogen reduces the LPS
      induced sickness behaviour and promotes recovery. These effects are associated
      with a shift towards anti-inflammatory gene expression profile at baseline
      (downregulation of TNF- alpha and upregulation of IL-10). In addition, molecular
      hydrogen increases the amplitude, but shortens the duration and promotes the
      extinction of neuroinflammation. Consistently, molecular hydrogen modulates the
      activation and gene expression in a similar fashion in immortalized murine
      microglia (BV-2 cell line), suggesting that the effects observed in vivo may
      involve the modulation of microglial activation. Taken together, our data point
      to the regulation of cytokine expression being an additional critical mechanism
      underlying the beneficial effects of molecular hydrogen.

PMID- 22860059
TI  - De novo sequencing of Hypericum perforatum transcriptome to identify potential
      genes involved in the biosynthesis of active metabolites.
AB  - BACKGROUND: Hypericum perforatum L. (St. John's wort) is a medicinal plant with
      pharmacological properties that are antidepressant, anti-inflammatory, antiviral,
      anti-cancer, and antibacterial. Its major active metabolites are hypericins,
      hyperforins, and melatonin. However, little genetic information is available for
      this species, especially that concerning the biosynthetic pathways for active
      ingredients. METHODOLOGY/PRINCIPAL FINDINGS: Using de novo transcriptome
      analysis, we obtained 59,184 unigenes covering the entire life cycle of these
      plants. In all, 40,813 unigenes (68.86%) were annotated and 2,359 were assigned
      to secondary metabolic pathways. Among them, 260 unigenes are involved in the
      production of hypericin, hyperforin, and melatonin. Another 2,291 unigenes are
      classified as potential Type III polyketide synthase. Our BlastX search against
      the AGRIS database reveals 1,772 unigenes that are homologous to 47 known
      Arabidopsis transcription factor families. Further analysis shows that 10.61%
      (6,277) of these unigenes contain 7,643 SSRs. CONCLUSION: We have identified a
      set of putative genes involved in several secondary metabolism pathways,
      especially those related to the synthesis of its active ingredients. Our results
      will serve as an important platform for public information about gene expression,
      genomics, and functional genomics in H. perforatum.

PMID- 22860060
TI  - EDTA improves stability of whole blood C-peptide and insulin to over 24 hours at
      room temperature.
AB  - INTRODUCTION: C-peptide and insulin measurements in blood provide useful
      information regarding endogenous insulin secretion. Conflicting evidence on
      sample stability and handling procedures continue to limit the widespread
      clinical use of these tests. We assessed the factors that altered the stability
      of insulin and C-peptide in blood. METHODS: We investigated the impact of
      preservative type, time to centrifugation, storage conditions and duration of
      storage on the stability of C-peptide and insulin on three different analytical
      platforms. RESULTS: C-peptide was stable for at least 24 hours at room
      temperature in both centrifuged and whole blood collected in K(+)-EDTA and serum
      gel tubes, with the exception of whole blood serum gel, which decreased to 78% of
      baseline at 24 hours, (p = 0.008). Insulin was stable at room temperature for 24
      hours in both centrifuged and whole blood collected in K(+)-EDTA tubes. In
      contrast insulin levels decreased in serum gel tubes both centrifuged and whole
      blood (66% of baseline, p = 0.01 and 76% of baseline p = 0.01, by 24 hours
      respectively). C-peptide and insulin remained stable after 6 freeze-thaw cycles.
      CONCLUSIONS: The stability of C-peptide and insulin in whole blood K(+)-EDTA
      tubes negates the need to conform to strict sample handling procedures for these
      assays, greatly increasing their clinical utility.

PMID- 22860062
TI  - Niche tracking and rapid establishment of distributional equilibrium in the house
      sparrow show potential responsiveness of species to climate change.
AB  - The ability of species to respond to novel future climates is determined in part
      by their physiological capacity to tolerate climate change and the degree to
      which they have reached and continue to maintain distributional equilibrium with
      the environment. While broad-scale correlative climatic measurements of a
      species' niche are often described as estimating the fundamental niche, it is
      unclear how well these occupied portions actually approximate the fundamental
      niche per se, versus the fundamental niche that exists in environmental space,
      and what fitness values bounding the niche are necessary to maintain
      distributional equilibrium. Here, we investigate these questions by comparing
      physiological and correlative estimates of the thermal niche in the introduced
      North American house sparrow (Passer domesticus). Our results indicate that
      occupied portions of the fundamental niche derived from temperature correlations
      closely approximate the centroid of the existing fundamental niche calculated on
      a fitness threshold of 50% population mortality. Using these niche measures, a 75
      year time series analysis (1930-2004) further shows that: (i) existing
      fundamental and occupied niche centroids did not undergo directional change, (ii)
      interannual changes in the two niche centroids were correlated, (iii)
      temperatures in North America moved through niche space in a net centripetal
      fashion, and consequently, (iv) most areas throughout the range of the house
      sparrow tracked the existing fundamental niche centroid with respect to at least
      one temperature gradient. Following introduction to a new continent, the house
      sparrow rapidly tracked its thermal niche and established continent-wide
      distributional equilibrium with respect to major temperature gradients. These
      dynamics were mediated in large part by the species' broad thermal physiological
      tolerances, high dispersal potential, competitive advantage in human-dominated
      landscapes, and climatically induced changes to the realized environmental space.
      Such insights may be used to conceptualize mechanistic climatic niche models in
      birds and other taxa.

PMID- 22860061
TI  - Cocaine withdrawal causes delayed dysregulation of stress genes in the
      hippocampus.
AB  - Relapse, even following an extended period of withdrawal, is a major challenge in
      substance abuse management. Delayed neurobiological effects of the drug during
      prolonged withdrawal likely contribute to sustained vulnerability to relapse.
      Stress is a major trigger of relapse, and the hippocampus regulates the magnitude
      and duration of stress responses. Recent work has implicated hippocampal
      plasticity in various aspects of substance abuse. We asked whether changes in
      stress regulatory mechanisms in the hippocampus may participate in the
      neuroadaptations that occur during prolonged withdrawal. We therefore examined
      changes in the rat stress system during the course of withdrawal from extended
      daily access (5-hours) of cocaine self-administration, an animal model of
      addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma
      corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR
      mRNA ratios) and expression of other stress-related molecules (HSP90AA1 and
      HSP90AB1 mRNA) were measured in hippocampal subfields using in situ
      hybridization. Results showed a delayed emergence of dysregulation of stress
      genes in the posterior hippocampus following 28 days of cocaine withdrawal. This
      included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG,
      and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively
      decreased during the course of withdrawal, were normalized following 28 days of
      withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA
      ratio in DG. These results suggest a role for the posterior hippocampus in the
      neuroadaptations that occur during prolonged withdrawal, and point to a signaling
      partner of GR, HSP90AA1, as a novel dysregulated target during cocaine
      withdrawal. These delayed neurobiological effects of extended cocaine exposure
      likely contribute to sustained vulnerability to relapse.

PMID- 22860063
TI  - Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1
      induced suppression of hepatic gluconeogenesis in type-2 diabetic mice.
AB  - The present study investigated the chronic efficacy of oleanolic acid (OA), a
      triterpenoid selected from our recent screening, on hyperglycemia in type-2
      diabetic mice. C57BL/6J mice were fed a high-fat diet followed by low doses of
      streptozotocin to generate a type-2 diabetic model. OA (100 mg/kg/day) was
      administered orally for 2 weeks with its effects monitored for 6 weeks. High-fat
      feeding and streptozotocin generated a steady hyperglycemia (21.2 +/- 1.1 mM) but
      OA administration reversed the hyperglycemia by ~60%. Interestingly, after the
      cessation of OA administration, the reversed hyperglycemia was sustained for the
      entire post-treatment period of the study (4 weeks) despite the reoccurrence of
      dyslipidemia. Examination of insulin secretion and pancreas morphology did not
      indicate improved beta-cell function as a likely mechanism. Urine glucose loss
      was decreased with substantial improvement of diabetic nephropathy after the OA
      treatment. Pair-feeding the OA-treated mice to an untreated group ruled out food
      intake as a main factor attributable for this sustained reduction in
      hyperglycemia. Studies with the use of glucose tracers revealed no increase in
      glucose influx into muscle, adipose tissue or liver in the OA-treated mice.
      Finally, we analyzed key regulators of gluconeogenesis in the liver and found
      significant increases in the phosphorylation of both Akt and FoxO1 after
      treatment with OA. Importantly, these increases were significantly correlated
      with a down-regulation of glucose-6-phosphatase expression. Our findings suggest
      triterpenoids are a potential source of new efficacious drugs for sustained
      control of hyperglycemia. The liver appears to be a major site of action,
      possibly by the suppression of hepatic glucose production via the Akt/FoxO1 axis.

PMID- 22860064
TI  - Developmental role of zebrafish protease-activated receptor 1 (PAR1) in the
      cardio-vascular system.
AB  - Thrombin receptor, F2R or PAR1 is a G-protein coupled receptor, located in the
      membrane of endothelial cells. It has been initially found to transduce signals
      in hemostasis, but recently also known to act in cancer and in vascular
      development. Mouse embryos lacking PAR1 function die from hemorrhages with
      varying frequency at midgestation. We have performed a survey of potential PAR1
      homologs in the zebrafish genome and identified a teleost ortholog of mammalian
      PAR1. Knockdown of par1 function in zebrafish embryos demonstrates a requirement
      for Par1 in cardio-vascular development. Furthermore, we show that function of
      Par1 requires the presence of a phylogenetically conserved proteolytic cleavage
      site and a second intracellular domain. Altogether our results demonstrate a high
      degree of conservation of PAR1 proteins in the vertebrate lineage in respect to
      amino acid sequence as well as protein function.

PMID- 22860065
TI  - The desmosomal armadillo protein plakoglobin regulates prostate cancer cell
      adhesion and motility through vitronectin-dependent Src signaling.
AB  - Plakoglobin (PG) is an armadillo protein that associates with both classic and
      desmosomal cadherins, but is primarily concentrated in mature desmosomes in
      epithelia. While reduced levels of PG have been reported in localized and hormone
      refractory prostate tumors, the functional significance of these changes is
      unknown. Here we report that PG expression is reduced in samples of a prostate
      tumor tissue array and inversely correlated with advancing tumor potential in 7
      PCa cell lines. Ectopically expressed PG enhanced intercellular adhesive
      strength, and attenuated the motility and invasion of aggressive cell lines,
      whereas silencing PG in less tumorigenic cells had the opposite effect. PG also
      regulated cell-substrate adhesion and motility through extracellular matrix (ECM)
      dependent inhibition of Src kinase, suggesting that PG's effects were not due
      solely to increased intercellular adhesion. PG silencing resulted in elevated
      levels of the ECM protein vitronectin (VN), and exposing PG-expressing cells to
      VN induced Src activity. Furthermore, increased VN levels and Src activation
      correlated with diminished expression of PG in patient tissues. Thus, PG may
      inhibit Src by keeping VN low. Our results suggest that loss of intercellular
      adhesion due to reduced PG expression might be exacerbated by activation of Src
      through a PG-dependent mechanism. Furthermore, PG down-regulation during PCa
      progression could contribute to the known VN-dependent promotion of PCa invasion
      and metastasis, demonstrating a novel functional interaction between desmosomal
      cell-cell adhesion and cell-substrate adhesion signaling axes in prostate cancer.

PMID- 22860066
TI  - Influence of omega-3 fatty acid status on the way rats adapt to chronic restraint
      stress.
AB  - Omega-3 fatty acids are important for several neuronal and cognitive functions.
      Altered omega-3 fatty acid status has been implicated in reduced resistance to
      stress and mood disorders. We therefore evaluated the effects of repeated
      restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient,
      control or omega-3 enriched diets from conception. We measured body weight,
      plasma corticosterone and hippocampus glucocorticoid receptors and correlated
      these data with emotional and depression-like behaviour assessed by their open
      field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose
      preference test and the startle response. We also determined their plasma and
      brain membrane lipid profiles by gas chromatography. Repeated restraint stress
      caused rats fed a control diet to lose weight. Their plasma corticosterone
      increased and they showed moderate behavioural changes, with increases only in
      grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3
      enriched diet had a lower stress-induced weight loss and plasma corticosterone
      peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited
      an increased startle response, a stress-induced decrease in locomotor activity
      and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary
      omega-3 fatty acids increased; diets containing preformed long-chain omega-3
      fatty acid were better than diets containing the precursor alpha-linolenic acid.
      However, the restraint stress reduced the amounts of omega-3 incorporated. These
      data showed that the response to chronic restraint stress was modulated by the
      omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment
      protecting against stress.

PMID- 22860067
TI  - Cortical thickness and behavior abnormalities in children born preterm.
AB  - AIM: To identify long-term effects of preterm birth and of periventricular
      leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between
      CTh and cognitive-behavioral abnormalities. METHODS: We performed brain magnetic
      resonance imaging on 22 preterm children with PVL, 14 preterm children with no
      evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with
      FreeSurfer software. All participants underwent cognitive and behavioral
      assessments by means of the Wechsler Intelligence Scales for Children-Fourth
      Edition (WISC-IV) and the Child Behavior Checklist (CBCL). RESULTS: We did not
      find global CTh differences between the groups. However, a thinner cortex was
      found in left postcentral, supramarginal, and caudal middle rostral gyri in
      preterm children with no evidence of PVL than in the full-term controls, while
      PVL preterm children showed thicker cortex in right pericalcarine and left
      rostral middle frontal areas than in preterm children with no evidence of PVL. In
      the PVL group, internalizing and externalizing scores correlated mainly with CTh
      in frontal areas. Attentional scores were found to be higher in PVL and
      correlated with CTh increments in right frontal areas. INTERPRETATION: The
      preterm group with no evidence of PVL, when compared with full-term children,
      showed evidence of a different pattern of regional thinning in the cortical gray
      matter. In turn, PVL preterm children exhibited atypical increases in CTh that
      may underlie their prevalent behavioral problems.

PMID- 22860068
TI  - Structural basis of the interaction of a Trypanosoma cruzi surface molecule
      implicated in oral infection with host cells and gastric mucin.
AB  - Host cell invasion and dissemination within the host are hallmarks of virulence
      for many pathogenic microorganisms. As concerns Trypanosoma cruzi, which causes
      Chagas disease, the insect vector-derived metacyclic trypomastigotes (MT)
      initiate infection by invading host cells, and later blood trypomastigotes
      disseminate to diverse organs and tissues. Studies with MT generated in vitro and
      tissue culture-derived trypomastigotes (TCT), as counterparts of insect-borne and
      bloodstream parasites, have implicated members of the gp85/trans-sialidase
      superfamily, MT gp82 and TCT Tc85-11, in cell invasion and interaction with host
      factors. Here we analyzed the gp82 structure/function characteristics and
      compared them with those previously reported for Tc85-11. One of the gp82
      sequences identified as a cell binding site consisted of an alpha-helix, which
      connects the N-terminal beta-propeller domain to the C-terminal beta-sandwich
      domain where the second binding site is nested. In the gp82 structure model, both
      sites were exposed at the surface. Unlike gp82, the Tc85-11 cell adhesion sites
      are located in the N-terminal beta-propeller region. The gp82 sequence
      corresponding to the epitope for a monoclonal antibody that inhibits MT entry
      into target cells was exposed on the surface, upstream and contiguous to the
      alpha-helix. Located downstream and close to the alpha-helix was the gp82 gastric
      mucin binding site, which plays a central role in oral T. cruzi infection. The
      sequences equivalent to Tc85-11 laminin-binding sites, which have been associated
      with the parasite ability to overcome extracellular matrices and basal laminae,
      was poorly conserved in gp82, compatible with its reduced capacity to bind
      laminin. Our study indicates that gp82 is structurally suited for MT to initiate
      infection by the oral route, whereas Tc85-11, with its affinity for laminin,
      would facilitate the parasite dissemination through diverse organs and tissues.

PMID- 22860069
TI  - ARID3B induces tumor necrosis factor alpha mediated apoptosis while a novel
      ARID3B splice form does not induce cell death.
AB  - Alternative splicing is a common occurrence in many cancers. Alternative splicing
      is linked with decreased apoptosis and chemoresistance in cancer cells. We
      previously demonstrated that ARID3B, a member of the AT-rich interactive domain
      (ARID) family of DNA binding proteins, is overexpressed in ovarian cancer.
      Therefore we wanted to assess the effect of ARID3B splice forms on cell
      viability. We identified a novel splice form of the ARID3B gene (designated as
      ARID3B Sh), which lacks the C-terminal exons 5-9 present in the full-length
      isoform (ARID3B Fl). ARID3B Fl is expressed in a variety of cancer cell lines.
      Expression of ARID3B Sh varied by cell type, but was highly expressed in most
      ovarian cancer lines. ARID3B is modestly transcriptionally activated by epidermal
      growth factor receptor (EGFR) signaling through the PEA3 transcription factor. We
      further found that ARID3B Fl is predominantly nuclear but is also present at the
      plasma membrane and in the cytosol. Endogenous ARID3B Sh is present in nuclear
      fractions, yet, when overexpressed ARID3B Sh accumulates in the cytosol and
      membrane fractions. The differential localization of these isoforms suggests they
      have different functions. Importantly, ARID3B Fl overexpression results in
      upregulation of pro-apoptotic BIM and induces Tumor Necrosis Factor alpha
      (TNFalpha) and TNF-related apoptosis inducing ligand (TRAIL) induced cell death.
      The ARID3B Fl-induced genes include TNFalpha, TRAIL, TRADD, TNF-R2, Caspase 10
      and Caspase 7. Interestingly, ARID3B Sh does not induce apoptosis or expression
      of these genes. ARID3B Fl induces death receptor mediated apoptosis while the
      novel splice form ARID3B Sh does not induce cell death. Therefore alternative
      splice forms of ARID3B may play different roles in ovarian cancer progression.

PMID- 22860070
TI  - Transcriptome analysis of early surface-associated growth of Shewanella
      oneidensis MR-1.
AB  - Bacterial biofilm formation starts with single cells attaching to a surface,
      however, little is known about the initial attachment steps and the adaptation to
      the surface-associated life style. Here, we describe a hydrodynamic system that
      allows easy harvest of cells at very early biofilm stages. Using the metal ion
      reducing gammaproteobacterium Shewanella oneidensis MR-1 as a model organism, we
      analyzed the transcriptional changes occurring during surface-associated growth
      between 15 and 60 minutes after attachment. 230 genes were significantly
      upregulated and 333 were downregulated by a factor of >= 2. Main functional
      categories of the corresponding gene products comprise metabolism, uptake and
      transport, regulation, and hypothetical proteins. Among the genes highly
      upregulated those implicated in iron uptake are highly overrepresented, strongly
      indicating that S. oneidensis MR-1 has a high demand for iron during surface
      attachment and initial biofilm stages. Subsequent microscopic analysis of biofilm
      formation under hydrodynamic conditions revealed that addition of Fe(II)
      significantly stimulated biofilm formation of S. oneidensis MR-1 while planktonic
      growth was not affected. Our approach to harvest cells for transcriptional
      analysis of early biofilm stages is expected to be easily adapted to other
      bacterial species.

PMID- 22860071
TI  - Identification of pluripotent and adult stem cell genes unrelated to cell cycle
      and associated with poor prognosis in multiple myeloma.
AB  - Gene expression-based scores used to predict risk in cancer frequently include
      genes coding for DNA replication, repair or recombination. Using two independent
      cohorts of 206 and 345 previously-untreated patients with Multiple Myeloma (MM),
      we identified 50 cell cycle-unrelated genes overexpressed in multiple myeloma
      cells (MMCs) compared to normal human proliferating plasmablasts and non
      proliferating bone marrow plasma cells and which have prognostic value for
      overall survival. Thirty-seven of these 50 myeloma genes (74%) were enriched in
      genes overexpressed in one of 3 normal human stem cell populations--pluripotent
      (18), hematopoietic (10) or mesenchymal stem cells (9)--and only three genes were
      enriched in one of 5 populations of differentiated cells (memory B lymphocytes, T
      lymphocytes, polymorphonuclear cells, monocytes, osteoclasts). These 37 genes
      shared by MMCs and adult or pluripotent stem cells were used to build a stem cell
      score ((SC)score), which proved to be strongly prognostic in the 2 independent
      cohorts of patients compared to other gene expression-based risk scores or usual
      clinical scores using multivariate Cox analysis. This finding highlights cell
      cycle-unrelated prognostic genes shared by myeloma cells and normal stem cells,
      whose products might be important for normal and malignant stem cell biology.

PMID- 22860072
TI  - Mercury-selenium relationships in liver of Guiana dolphin: the possible role of
      Kupffer cells in the detoxification process by tiemannite formation.
AB  - Top marine predators present high mercury concentrations in their tissues as
      consequence of biomagnification of the most toxic form of this metal,
      methylmercury (MeHg). The present study concerns mercury accumulation by Guiana
      dolphins (Sotalia guianensis), highlighting the selenium-mediated methylmercury
      detoxification process. Liver samples from 19 dolphins incidentally captured
      within Guanabara Bay (Rio de Janeiro State, Brazil) from 1994 to 2006 were
      analyzed for total mercury (THg), methylmercury (MeHg), total organic mercury
      (TOrgHg) and selenium (Se). X-ray microanalyses were also performed. The
      specimens, including from fetuses to 30-year-old dolphins, comprising 8 females
      and 11 males, presented high THg (0.53-132 ug/g wet wt.) and Se concentrations
      (0.17-74.8 ug/g wet wt.). Correlations between THg, MeHg, TOrgHg and Se were
      verified with age (p<0.05), as well as a high and positive correlation was
      observed between molar concentrations of Hg and Se (p<0.05). Negative
      correlations were observed between THg and the percentage of MeHg contribution to
      THg (p<0.05), which represents a consequence of the selenium-mediated
      methylmercury detoxification process. Accumulation of Se-Hg amorphous crystals in
      Kupffer Cells was demonstrated through ultra-structural analysis, which shows
      that Guiana dolphin is capable of carrying out the demethylation process via
      mercury selenide formation.

PMID- 22860073
TI  - Penguin chicks benefit from elevated yolk androgen levels under sibling
      competition.
AB  - Crested penguins (genus Eudyptes) have a peculiar hatching pattern, with the
      first-laid egg (A-egg) hatching after the second-laid egg (B-egg) and chicks from
      A-eggs typically having a much lower survival probability. Maternal yolk
      androgens have been suggested to contribute to the competitive superiority of the
      B-chick in southern rockhopper penguins Eudyptes chrysocome, given their
      important role in mediating sibling competition in other species. We therefore
      increased the yolk androgen levels in freshly-laid eggs and examined the
      consequences for sibling competition--via effects on embryonic developmental
      times, chick growth and early survival. We placed one androgen-treated egg and
      one control egg into each foster nest, matching them for mass, laying date and
      laying order. The androgen treatment did not significantly affect embryonic
      developmental times or chick measurements at hatching. However, elevated yolk
      androgen levels benefitted chick growth in interaction with the number of
      siblings in a brood. Chicks from androgen-treated eggs had faster growth in the
      presence of a sibling than chicks from control eggs. Under these circumstances
      they also had a higher survival probability. Thus maternal androgens appear to
      reinforce the observed hatching pattern, facilitating brood reduction. This
      contrasts to most previous studies in other species where yolk androgens have
      been shown to compensate for the negative consequences of delayed hatching within
      the brood hierarchy.

PMID- 22860074
TI  - When to hold that thought: an experimental study showing reduced inhibition of
      pre-trained associations in schizophrenia.
AB  - Schizophrenia encompasses a wide variety of cognitive dysfunctions, a number of
      which can be understood as deficits of inhibition. To date, no research has
      examined 'conditioned inhibition' in schizophrenia--the ability of a stimulus
      that signals the absence of an expected outcome to counteract the conditioned
      response produced by a signal for that outcome (a conditioned excitor). A
      computer-based task was used to measure conditioned excitation and inhibition in
      the same discrimination procedure, in 25 patients with a confirmed diagnosis of
      schizophrenia and a community-based comparison sample. Conditioned inhibition was
      measured by a ratio score, which compared the degree to which the inhibitory
      stimulus and a neutral control stimulus reduced conditioned responding to the
      excitatory cue: the lower the ratio, the greater the inhibitory learning. At test
      the ratios were 0.45 and 0.39 for patient and control groups respectively, and
      the relevant interaction term of the ANOVA confirmed that the degree of
      inhibition was reduced in the patient group, with an effect size of r =
      0.28.These results demonstrate for the first time that inhibitory learning is
      impaired in schizophrenia. Such an impairment provides an attractive framework
      for the interpretation of the positive symptoms of schizophrenia. However, we
      were unable to demonstrate any relationship between the level of conditioned
      inhibition and medication. Similarly, in the present study it must be emphasised
      that the available data did not demonstrate any relationship between individual
      variation in inhibitory learning and the level of positive symptoms as measured
      by the PANSS. In fact inhibitory learning impairment was relatively greater in
      participants with a predominantly negative symptom profile and their excitatory
      learning was also reduced. Accordingly the next step will be to investigate such
      relationships in a larger sample with a priori defined sub-groups displaying
      predominantly positive versus predominantly negative symptoms.

PMID- 22860075
TI  - A role for Toll-like receptor mediated signals in neutrophils in the pathogenesis
      of the anti-phospholipid syndrome.
AB  - The anti-phospholipid syndrome (APS) is characterized by recurrent thrombosis and
      occurrence of anti-phospholipid antibodies (aPL). aPL are necessary, but not
      sufficient for the clinical manifestations of APS. Growing evidence suggests a
      role of innate immune cells, in particular polymorphonuclear neutrophils (PMN)
      and Toll-like receptors (TLR) to be additionally involved. aPL activate
      endothelial cells and monocytes through a TLR4-dependent signalling pathway.
      Whether this is also relevant for PMN in a similar way is currently not known. To
      address this issue, we used purified PMN from healthy donors and stimulated them
      in the presence or absence of human monoclonal aPL and the TLR4 agonist LPS
      monitoring neutrophil effector functions, namely the oxidative burst,
      phagocytosis, L-Selectin shedding and IL-8 production. aPL alone were only able
      to induce minor activation of PMN effector functions at high concentrations.
      However, in the additional presence of LPS the activation threshold was markedly
      lower indicating a synergistic activation pathway of aPL and TLR in PMN. In
      summary, our results indicate that PMN effector functions are directly activated
      by aPL and boosted by the additional presence of microbial products. This
      highlights a role for PMN as important innate immune effector cells that
      contribute to the pathophysiology of APS.

PMID- 22860076
TI  - Evidence to suggest that teeth act as human ornament displays signalling mate
      quality.
AB  - Ornament displays seen in animals convey information about genetic quality,
      developmental history and current disease state to both prospective sexual
      partners and potential rivals. In this context, showing of teeth through smiles
      etc is a characteristic feature of human social interaction. Tooth development is
      influenced by genetic and environmental factors. Adult teeth record environmental
      and traumatic events, as well as the effects of disease and ageing. Teeth are
      therefore a rich source of information about individuals and their histories.
      This study examined the effects of digital manipulations of tooth colour and
      spacing. Results showed that deviation away from normal spacing and/or the
      presence of yellowed colouration had negative effects on ratings of
      attractiveness and that these effects were markedly stronger in female models.
      Whitening had no effect beyond that produced by natural colouration. This
      indicates that these colour induced alterations in ratings of attractiveness are
      mediated by increased/decreased yellowing rather than whitening per se. Teeth
      become yellower and darker with age. Therefore it is suggested that whilst the
      teeth of both sexes act as human ornament displays, the female display is more
      complex because it additionally signals residual reproductive value.

PMID- 22860077
TI  - Remote ischemic conditioning to protect against ischemia-reperfusion injury: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Remote ischemic conditioning is gaining interest as potential method
      to induce resistance against ischemia reperfusion injury in a variety of clinical
      settings. We performed a systematic review and meta-analysis to investigate
      whether remote ischemic conditioning reduces mortality, major adverse
      cardiovascular events, length of stay in hospital and in the intensive care unit
      and biomarker release in patients who suffer from or are at risk for ischemia
      reperfusion injury. METHODS AND RESULTS: Medline, EMBASE and Cochrane databases
      were searched for randomized clinical trials comparing remote ischemic
      conditioning, regardless of timing, with no conditioning. Two investigators
      independently selected suitable trials, assessed trial quality and extracted
      data. 23 studies in patients undergoing cardiac surgery (15 studies),
      percutaneous coronary intervention (four studies) and vascular surgery (four
      studies), comprising in total 1878 patients, were included in this review.
      Compared to no conditioning, remote ischemic conditioning did not reduce
      mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse
      cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial
      infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as
      was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]).
      CONCLUSION: There is no evidence that remote ischemic conditioning reduces
      mortality associated with ischemic events; nor does it reduce major adverse
      cardiovascular events. However, remote ischemic conditioning did reduce the
      incidence of peri-procedural myocardial infarctions, as well as the release of
      troponin.

PMID- 22860078
TI  - Entry tropism of BK and Merkel cell polyomaviruses in cell culture.
AB  - Merkel Cell Polyomavirus (MCV or MCPyV) was recently discovered in an aggressive
      form of skin cancer known as Merkel cell carcinoma (MCC). Integration of MCV DNA
      into the host genome likely contributes to the development of MCC in humans. MCV
      infection is common and many healthy people shed MCV virions from the surface of
      their skin. MCV DNA has also been detected in samples from a variety of other
      tissues. Although MCC tumors serve as a record that MCV can infect the Merkel
      cell lineage, the true tissue tropism and natural reservoirs of MCV infection in
      the host are not known. In an effort to gain insight into the tissue tropism of
      MCV, and to possibly identify cellular factors responsible for mediating
      infectious entry of the virus, the infection potential of human cells derived
      from a variety of tissues was evaluated. MCV gene transfer vectors
      (pseudoviruses) carrying reporter plasmid DNA encoding GFP or luciferase genes
      were used to transduce keratinocytes and melanocytes, as well as lines derived
      from MCC tumors and the NCI-60 panel of human tumor cell lines. MCV transduction
      was compared to transduction with pseudoviruses based on the better-studied human
      BK polyomavirus (BKV). The efficiency of MCV and BKV transduction of various cell
      types occasionally overlapped, but often differed greatly, and no clear tissue
      type preference emerged. Application of native MCV virions to a subset of highly
      transducible cell types suggested that the lines do not support robust
      replication of MCV, consistent with recent proposals that the MCV late phase may
      be governed by cellular differentiation in vivo. The availability of carefully
      curated gene expression data for the NCI-60 panel should make the MCV and BKV
      transduction data for these lines a useful reference for future studies aimed at
      elucidation of the infectious entry pathways of these viruses.

PMID- 22860079
TI  - Functional characterizations of RIG-I to GCRV and viral/bacterial PAMPs in grass
      carp Ctenopharyngodon idella.
AB  - BACKGROUND: RIG-I (retinoic acid inducible gene-I) is one of the key cytosolic
      pattern recognition receptors (PRRs) for detecting nucleotide pathogen associated
      molecular patterns (PAMPs) and mediating the induction of type I interferon and
      inflammatory cytokines in innate immune response. Though the mechanism is well
      characterized in mammals, the study of the accurate function of RIG-I in teleosts
      is still in its infancy. METHODOLOGY/PRINCIPAL FINDINGS: To clarify the
      functional characterizations of RIG-I in grass carp Ctenopharyngodon idella
      (CiRIG-I), six representative overexpression plasmids were constructed and
      transfected into C. idella kidney (CIK) cell lines to obtain stably expressing
      recombinant proteins, respectively. A virus titer test and 96-well plate staining
      assay showed that all constructs exhibited the antiviral activity somewhat. The
      quantitative real-time RT-PCR (qRT-PCR) demonstrated that mRNA expressions of
      CiIPS-1, CiIFN-I and CiMx2 were regulated by not only virus (GCRV) or viral PAMP
      (poly(IC)) challenge but also bacterial PAMPs (LPS and PGN) stimulation in the
      steadily transfected cells. The results showed that the full-length CiRIG-I
      played a key role in RLR pathway. The repressor domain (RD) exerted an inhibitory
      function of the signaling channel under all utilized challenges. Caspase
      activation and recruitment domains (CARDs) showed a positive role in GCRV and
      poly(I:C) challenge. Helicase motifs were crucial for the signaling pathway upon
      LPS and PGN stimulation. Interestingly, DeltaCARDs (CARDs deleted) showed
      positive modulation in RIG-I signal transduction. CONCLUSIONS/SIGNIFICANCE: The
      results provided some novel insights into RIG-I sensing with a strikingly broad
      regulation in teleosts, responding not only to the dsRNA virus or synthetic dsRNA
      but also bacterial PAMPs.

PMID- 22860080
TI  - Long-term hepatitis B virus (HBV) response to lamivudine-containing highly active
      antiretroviral therapy in HIV-HBV co-infected patients in Thailand.
AB  - BACKGROUND: Approximately 4 million of people are co-infected with HIV and
      Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV
      infected patients initiate first-line highly active antiretroviral therapy
      containing lamivudine (3TC-containing-HAART) and long-term virological response
      of HBV to lamivudine-containing HAART in co-infected patients is not well known.
      METHODOLOGY/PRINCIPAL FINDING: HIV-HBV co-infected patients enrolled in the PHPT
      cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART
      regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine
      transaminase were measured at baseline, 3 months, 12 months and then every 6
      months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative
      rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co
      infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC
      containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10) IU/mL and
      4.47 log(10) copies/mL, respectively. At 12 months, 67% of patients achieved HBV
      DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive.
      Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative
      rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV
      DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17
      patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost
      HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit
      (median duration, 59 months). HBV breakthrough was observed only in HBeAg
      positive patients and 6 of 7 patients presenting HBV breakthrough had the
      rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or
      rtV173L. CONCLUSIONS: All HBeAg-negative patients and 63% of HBeAg-positive HIV
      HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC
      containing-HAART. This study provides information useful for the management of co
      infected patients in resource-limited countries where the vast majority of co
      infected patients are currently receiving 3TC.

PMID- 22860081
TI  - Subcellular localization of iron and heme metabolism related proteins at early
      stages of erythrophagocytosis.
AB  - BACKGROUND: Senescent red blood cells (RBC) are recognized, phagocytosed and
      cleared by tissue macrophages. During this erythrophagocytosis (EP), RBC are
      engulfed and processed in special compartments called erythrophagosomes. We
      previously described that following EP, heme is rapidly degraded through the
      catabolic activity of heme oxygenase (HO). Extracted heme iron is then either
      exported or stored by macrophages. However, the cellular localization of the
      early steps of heme processing and iron extraction during EP remains to be
      clearly defined. METHODOLOGY/PRINCIPAL FINDINGS: We took advantage of our
      previously described cellular model of EP, using bone marrow-derived macrophages
      (BMDM). The subcellular localization of both inducible and constitutive isoforms
      of HO (HO-1 and HO-2), of the divalent metal transporters (Nramp1, Nramp2/DMT1,
      Fpn), and of the recently identified heme transporter HRG-1, was followed by
      fluorescence and electron microscopy during the earliest steps of EP. We also
      looked at some ER [calnexin, glucose-6-phosphatase (G6Pase) activity] and
      lysosomes (Lamp1) markers during EP. In both quiescent and LPS-activated BMDM,
      Nramp1 and Lamp1 were shown to be strong markers of the erythrophagolysosomal
      membrane. HRG-1 was also recruited to the erythrophagosome. Furthermore, we
      observed calnexin labeling and G6Pase activity at the erythrophagosomal membrane,
      indicating the contribution of ER in this phagocytosis model. In contrast,
      Nramp2/DMT1, Fpn, HO-1 and HO-2 were not detected at the membrane of
      erythrophagosomes. CONCLUSIONS/SIGNIFICANCE: Our study highlights the subcellular
      localization of various heme- and iron-related proteins during early steps of EP,
      thereby suggesting a model for heme catabolism occurring outside the phagosome,
      with heme likely being transported into the cytosol through HRG1. The precise
      function of Nramp1 at the phagosomal membrane in this model remains to be
      determined.

PMID- 22860082
TI  - Multiple SNP markers reveal fine-scale population and deep phylogeographic
      structure in European anchovy (Engraulis encrasicolus L.).
AB  - Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and
      mitochondrial DNA (mtDNA) have detected several genetic subdivisions among
      European anchovy populations. However, these studies have been limited in their
      power to detect some aspects of population structure by the use of a single or a
      few molecular markers, or by limited geographic sampling. We use a multi-marker
      approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze
      626 European anchovies from the whole range of the species to resolve shallow and
      deep levels of population structure. Nuclear SNPs define 10 genetic entities
      within two larger genetically distinctive groups associated with oceanic
      variables and different life-history traits. MtDNA SNPs define two deep
      phylogroups that reflect ancient dispersals and colonizations. These markers
      define two ecological groups. One major group of Iberian-Atlantic populations is
      associated with upwelling areas on narrow continental shelves and includes
      populations spawning and overwintering in coastal areas. A second major group
      includes northern populations in the North East (NE) Atlantic (including the Bay
      of Biscay) and the Mediterranean and is associated with wide continental shelves
      with local larval retention currents. This group tends to spawn and overwinter in
      oceanic areas. These two groups encompass ten populations that differ from
      previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay
      of Biscay regions. In addition, a new North Sea-English Channel stock is defined.
      SNPs indicate that some populations in the Bay of Biscay are genetically closer
      to North Western (NW) Mediterranean populations than to other populations in the
      NE Atlantic, likely due to colonizations of the Bay of Biscay and NW
      Mediterranean by migrants from a common ancestral population. Northern NE
      Atlantic populations were subsequently established by migrants from the Bay of
      Biscay. Populations along the Iberian-Atlantic coast appear to have been founded
      by secondary waves of migrants from a southern refuge.

PMID- 22860083
TI  - Correlates of reported and recorded time spent in physical activity in working
      adults: results from the commuting and health in Cambridge study.
AB  - BACKGROUND: The correlates of physical activity in adults are relatively well
      studied. However, many studies use self-reported ('reported') measures of
      activity and we know little about the possible differences between the correlates
      of reported and objective ('recorded') measures of physical activity. We compared
      the correlates of reported and recorded time spent in moderate-to-vigorous
      physical activity (MVPA) in a sample of working adults. METHODS: In 2009,
      participants in the Commuting and Health in Cambridge study completed
      questionnaires assessing individual, socio-demographic, health and contextual
      characteristics. Recorded time spent in MVPA over seven days was ascertained
      using accelerometers and reported time spent in MVPA was assessed using the
      Recent Physical Activity Questionnaire (RPAQ). Correlates of MVPA were
      investigated using sex-specific linear regression models. RESULTS: 486
      participants (70% women) provided both reported and recorded physical activity
      data. 89% recorded at least 30 minutes of MVPA per day. In men, none of the
      potential explanatory variables were associated with both reported and recorded
      time spent in MVPA. In women, of all the potential explanatory variables only
      that of having a standing or manual occupation was associated with both reported
      (+42 min/day; 95% CI 16.4 to 68.4, p = 0.001) and recorded (+9 min/day; 95% CI:
      3.5 to 15.7, p = 0.002) time spent in MVPA. DISCUSSION: The use of an objective
      measure of physical activity may influence the correlates which are observed.
      Researchers may wish to consider using and analysing recorded and reported
      measures in combination to gain a more complete view of the correlates of
      physical activity.

PMID- 22860084
TI  - Avian BMR in marine and non-marine habitats: a test using shorebirds.
AB  - Basal metabolic rate (BMR) is closely linked to different habitats and way of
      life. In birds, some studies have noted that BMR is higher in marine species
      compared to those inhabiting terrestrial habitats. However, the extent of such
      metabolic dichotomy and its underlying mechanisms are largely unknown. Migratory
      shorebirds (Charadriiformes) offer a particularly interesting opportunity for
      testing this marine-non-marine difference as they are typically divided into two
      broad categories in terms of their habitat occupancy outside the breeding season:
      'coastal' and 'inland' shorebirds. Here, we measured BMR for 12 species of
      migratory shorebirds wintering in temperate inland habitats and collected
      additional BMR values from the literature for coastal and inland shorebirds along
      their migratory route to make inter- and intraspecific comparisons. We also
      measured the BMR of inland and coastal dunlins Calidris alpina wintering at a
      similar latitude to facilitate a more direct intraspecific comparison. Our
      interspecific analyses showed that BMR was significantly lower in inland
      shorebirds than in coastal shorebirds after the effects of potentially
      confounding climatic (latitude, temperature, solar radiation, wind conditions)
      and organismal (body mass, migratory status, phylogeny) factors were accounted
      for. This indicates that part of the variation in basal metabolism might be
      attributed to genotypic divergence. Intraspecific comparisons showed that the
      mass-specific BMR of dunlins wintering in inland freshwater habitats was 15%
      lower than in coastal saline habitats, suggesting that phenotypic plasticity also
      plays an important role in generating these metabolic differences. We propose
      that the absence of tidally-induced food restrictions, low salinity, and less
      windy microclimates associated with inland freshwater habitats may reduce the
      levels of energy expenditure, and hence BMR. Further research including common
      garden experiments that eliminate phenotypic plasticity as a source of phenotypic
      variation is needed to determine to what extent these general patterns are
      attributable to genotypic adaptation.

PMID- 22860085
TI  - CDK5RAP3 is a novel repressor of p14ARF in hepatocellular carcinoma cells.
AB  - CDK5 regulatory subunit associated protein 3 (CDK5RAP3) is a novel activator of
      PAK4 and processes important pro-metastatic function in hepatocarcinogenesis.
      However, it remains unclear if there are other mechanisms by which CDK5RAP3
      promotes HCC metastasis. Here, we showed that in CDK5RAP3 stable knockdown SMMC
      7721 HCC cells, p14(ARF) tumor suppressor was upregulated at protein and mRNA
      levels, and ectopic expression of CDK5RAP3 was found to repress the transcription
      of p14(ARF). Using chromatin immunoprecipitation assay, we demonstrated that
      CDK5RAP3 bound to p14(ARF) promoter in vivo. Furthermore, knockdown of p14(ARF)
      in CDK5RAP3 stable knockdown HCC cells reversed the suppression of HCC cell
      invasiveness mediated by knockdown of CDK5RAP3. Taken together, our findings
      provide the new evidence that overexpression of CDK5RAP3 promotes HCC metastasis
      via downregulation of p14(ARF).

PMID- 22860086
TI  - Dahl (S x R) congenic strain analysis confirms and defines a chromosome 5 female
      specific blood pressure quantitative trait locus to <7 Mbp.
AB  - The detection of multiple sex-specific blood pressure (BP) quantitative trait
      loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross
      male and female rat cohorts confirms clinical observations of sex-specific
      disease cause and response to treatment among hypertensive patients, and mandate
      the identification of sex-specific hypertension genes/mechanisms. We developed
      and studied two congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome
      5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2
      QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high
      salt diet (8% NaCl) challenge, identified only S.R5B congenic rats with lower SBP
      (-26.5 mmHg, P = 0.002), DBP (-23.7 mmHg, P = 0.004) and MAP (-25.1 mmHg, P =
      0.002) compared with Dahl S female controls at four months of age confirming BP
      f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B congenic segment did not
      affect pulse pressure and relative heart weight indicating that the gene
      underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy.
      The results of our congenic analysis narrowed BP-f1 to chromosome 5 coordinates
      134.9-141.5 Mbp setting up the basis for further fine mapping of BP-f1 and
      eventual identification of the specific gene variant accounting for BP-f1 effect
      on blood pressure.

PMID- 22860087
TI  - Quantitative image analysis and modeling indicate the Agrobacterium tumefaciens
      type IV secretion system is organized in a periodic pattern of foci.
AB  - The Gram negative plant pathogen Agrobacterium tumefaciens is uniquely capable of
      genetically transforming eukaryotic host cells during the infection process. DNA
      and protein substrates are transferred into plant cells via a type IV secretion
      system (T4SS), which forms large cell-envelope spanning complexes at multiple
      sites around the bacterial circumference. To gain a detailed understanding of
      T4SS positioning, the spatial distribution of fluorescently labeled T4SS
      components was quantitatively assessed to distinguish between random and
      structured localization processes. Through deconvolution microscopy followed by
      Fourier analysis and modeling, T4SS foci were found to localize in a non-random
      periodic pattern. These results indicate that T4SS complexes are dependent on an
      underlying scaffold or assembly process to obtain an organized distribution
      suitable for effective delivery of substrates into host cells.

PMID- 22860088
TI  - Light-induced oxidative stress, N-formylkynurenine, and oxygenic photosynthesis.
AB  - Light stress in plants results in damage to the water oxidizing reaction center,
      photosystem II (PSII). Redox signaling, through oxidative modification of amino
      acid side chains, has been proposed to participate in this process, but the
      oxidative signals have not yet been identified. Previously, we described an
      oxidative modification, N-formylkynurenine (NFK), of W365 in the CP43 subunit.
      The yield of this modification increases under light stress conditions, in
      parallel with the decrease in oxygen evolving activity. In this work, we show
      that this modification, NFK365-CP43, is present in thylakoid membranes and may be
      formed by reactive oxygen species produced at the Mn(4)CaO(5) cluster in the
      oxygen-evolving complex. NFK accumulation correlates with the extent of
      photoinhibition in PSII and thylakoid membranes. A modest increase in ionic
      strength inhibits NFK365-CP43 formation, and leads to accumulation of a new,
      light-induced NFK modification (NFK317) in the D1 polypeptide. Western analysis
      shows that D1 degradation and oligomerization occur under both sets of
      conditions. The NFK modifications in CP43 and D1 are found 17 and 14 Angstrom
      from the Mn(4)CaO(5) cluster, respectively. Based on these results, we propose
      that NFK is an oxidative modification that signals for damage and repair in PSII.
      The data suggest a two pathway model for light stress responses. These pathways
      involve differential, specific, oxidative modification of the CP43 or D1
      polypeptides.

PMID- 22860089
TI  - Loss of abdominal muscle in Pitx2 mutants associated with altered axial
      specification of lateral plate mesoderm.
AB  - Sequence specific transcription factors (SSTFs) combinatorially define cell types
      during development by forming recursively linked network kernels. Pitx2
      expression begins during gastrulation, together with Hox genes, and becomes
      localized to the abdominal lateral plate mesoderm (LPM) before the onset of
      myogenesis in somites. The somatopleure of Pitx2 null embryos begins to grow
      abnormally outward before muscle regulatory factors (MRFs) or Pitx2 begin
      expression in the dermomyotome/myotome. Abdominal somites become deformed and
      stunted as they elongate into the mutant body wall, but maintain normal MRF
      expression domains. Subsequent loss of abdominal muscles is therefore not due to
      defects in specification, determination, or commitment of the myogenic lineage.
      Microarray analysis was used to identify SSTF families whose expression levels
      change in E10.5 interlimb body wall biopsies. All Hox9-11 paralogs had lower RNA
      levels in mutants, whereas genes expressed selectively in the hypaxial
      dermomyotome/myotome and sclerotome had higher RNA levels in mutants. In situ
      hybridization analyses indicate that Hox gene expression was reduced in parts of
      the LPM and intermediate mesoderm of mutants. Chromatin occupancy studies
      conducted on E10.5 interlimb body wall biopsies showed that Pitx2 protein
      occupied chromatin sites containing conserved bicoid core motifs in the vicinity
      of Hox 9-11 and MRF genes. Taken together, the data indicate that Pitx2 protein
      in LPM cells acts, presumably in combination with other SSTFs, to repress gene
      expression, that are normally expressed in physically adjoining cell types. Pitx2
      thereby prevents cells in the interlimb LPM from adopting the stable network
      kernels that define sclerotomal, dermomyotomal, or myotomal mesenchymal cell
      types. This mechanism may be viewed either as lineage restriction or
      specification.

PMID- 22860090
TI  - Neural mechanisms underlying the cost of task switching: an ERP study.
AB  - BACKGROUND: When switching from one task to a new one, reaction times are
      prolonged. This phenomenon is called switch cost (SC). Researchers have recently
      used several kinds of task-switching paradigms to uncover neural mechanisms
      underlying the SC. Task-set reconfiguration and passive dissipation of a
      previously relevant task-set have been reported to contribute to the cost of task
      switching. METHODOLOGY/PRINCIPAL FINDINGS: An unpredictable cued task-switching
      paradigm was used, during which subjects were instructed to switch between a
      color and an orientation discrimination task. Electroencephalography (EEG) and
      behavioral measures were recorded in 14 subjects. Response-stimulus interval
      (RSI) and cue-stimulus interval (CSI) were manipulated with short and long
      intervals, respectively. Switch trials delayed reaction times (RTs) and increased
      error rates compared with repeat trials. The SC of RTs was smaller in the long
      CSI condition. For cue-locked waveforms, switch trials generated a larger
      parietal positive event-related potential (ERP), and a larger slow parietal
      positivity compared with repeat trials in the short and long CSI condition.
      Neural SC of cue-related ERP positivity was smaller in the long RSI condition.
      For stimulus-locked waveforms, a larger switch-related central negative ERP
      component was observed, and the neural SC of the ERP negativity was smaller in
      the long CSI. Results of standardized low resolution electromagnetic tomography
      (sLORETA) for both ERP positivity and negativity showed that switch trials evoked
      larger activation than repeat trials in dorsolateral prefrontal cortex (DLPFC)
      and posterior parietal cortex (PPC). CONCLUSIONS/SIGNIFICANCE: The results
      provide evidence that both RSI and CSI modulate the neural activities in the
      process of task-switching, but that these have a differential role during task
      set reconfiguration and passive dissipation of a previously relevant task-set.

PMID- 22860091
TI  - RhoT1 and Smad4 are correlated with lymph node metastasis and overall survival in
      pancreatic cancer.
AB  - Cancer cell invasion and metastasis are the most important adverse prognostic
      factors for pancreatic cancer. Identification of biomarkers associated with
      outcome of pancreatic cancer may provide new approaches and targets for
      anticancer therapy. The aim of this study is to examine the relationship between
      the expression of RhoT1, Smad4 and p16 and metastasis and survival in patients
      with pancreatic cancer. The analysis showed that the high cytoplasmic expression
      levels of RhoT1, Smad4 and p16 in pancreatic cancer tissues had significantly
      negative correlation with lymph node metastasis (LNM) (P = 0.017, P = 0.032, P =
      0.042, respectively). However, no significant association was observed between
      perineural invasion (PNI) and the expression of above three proteins (all
      P>0.05). Additionally, the survival analysis showed that the low expression
      levels of RhoT1 and Smad4 were significantly associated with worse survival (P =
      0.034, P = 0.047, respectively). In conclusion, these results indicated that the
      low-expression levels of RhoT1 and Smad4 were significantly associated with LNM
      and shorter survival. RhoT1 may be considered as a potential novel marker for
      predicting the outcome in patients with pancreatic cancer.

PMID- 22860092
TI  - Intense passionate love attenuates cigarette cue-reactivity in nicotine-deprived
      smokers: an FMRI study.
AB  - Self-expanding experiences like falling in love or engaging in novel, exciting
      and interesting activities activate the same brain reward mechanism (mesolimbic
      dopamine pathway) that reinforces drug use and abuse, including tobacco smoking.
      This suggests the possibility that reward from smoking is substitutable by self
      expansion (through competition with the same neural system), potentially aiding
      cessation efforts. Using a model of self-expansion in the context of romantic
      love, the present fMRI experiment examined whether, among nicotine-deprived
      smokers, relationship self-expansion is associated with deactivation of cigarette
      cue-reactivity regions. Results indicated that among participants who were
      experiencing moderate levels of craving, cigarette cue-reactivity regions (e.g.,
      cuneus and posterior cingulate cortex) showed significantly less activation
      during self-expansion conditions compared with control conditions. These results
      provide evidence that rewards from one domain (self-expansion) can act as a
      substitute for reward from another domain (nicotine) to attenuate cigarette cue
      reactivity.

PMID- 22860093
TI  - Drosophila regulate yeast density and increase yeast community similarity in a
      natural substrate.
AB  - Drosophila melanogaster adults and larvae, but especially larvae, had profound
      effects on the densities and community structure of yeasts that developed in
      banana fruits. Pieces of fruit exposed to adult female flies previously fed fly
      conditioned bananas developed higher yeast densities than pieces of the same
      fruits that were not exposed to flies, supporting previous suggestions that adult
      Drosophila vector yeasts to new substrates. However, larvae alone had dramatic
      effects on yeast density and species composition. When yeast densities were
      compared in pieces of the same fruits assigned to different treatments, fruits
      that developed low yeast densities in the absence of flies developed
      significantly higher yeast densities when exposed to larvae. Across all of the
      fruits, larvae regulated yeast densities within narrow limits, as compared to a
      much wider range of yeast densities that developed in pieces of the same fruits
      not exposed to flies. Larvae also affected yeast species composition,
      dramatically reducing species diversity across fruits, reducing variation in
      yeast communities from one fruit to the next (beta diversity), and encouraging
      the consistent development of a yeast community composed of three species of
      yeast (Candida californica, C. zemplinina, and Pichia kluvyeri), all of which
      were palatable to larvae. Larvae excreted viable cells of these three yeast
      species in their fecal pools, and discouraged the growth of filamentous fungi,
      processes which may have contributed to their effects on the yeast communities in
      banana fruits. These and other findings suggest that D. melanogaster adults and
      their larval offspring together engage in 'niche construction', facilitating a
      predictable microbial environment in the fruit substrates in which the larvae
      live and develop.

PMID- 22860094
TI  - Expression of PPARgamma and paraoxonase 2 correlated with Pseudomonas aeruginosa
      infection in cystic fibrosis.
AB  - The Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxododecanoyl-l
      homoserine lactone (3OC(12)HSL) can inhibit function of the mammalian anti
      inflammatory transcription factor peroxisome proliferator activated receptor
      (PPAR)gamma, and can be degraded by human paraoxonase (PON)2. Because 3OC(12)HSL
      is detected in lungs of cystic fibrosis (CF) patients infected with P.
      aeruginosa, we investigated the relationship between P. aeruginosa infection and
      gene expression of PPARgamma and PON2 in bronchoalveolar lavage fluid (BALF) of
      children with CF. Total RNA was extracted from cell pellets of BALF from 43
      children aged 6 months-5 years and analyzed by reverse transcription-quantitative
      real time PCR for gene expression of PPARgamma, PON2, and P. aeruginosa lasI, the
      3OC(12)HSL synthase. Patients with culture-confirmed P. aeruginosa infection had
      significantly lower gene expression of PPARgamma and PON2 than patients without
      P. aeruginosa infection. All samples that were culture-positive for P. aeruginosa
      were also positive for lasI expression. There was no significant difference in
      PPARgamma or PON2 expression between patients without culture-detectable
      infection and those with non-Pseudomonal bacterial infection, so reduced
      expression was specifically associated with P. aeruginosa infection. Expression
      of both PPARgamma and PON2 was inversely correlated with neutrophil counts in
      BALF, but showed no correlation with other variables evaluated. Thus, lower
      PPARgamma and PON2 gene expression in the BALF of children with CF is associated
      specifically with P. aeruginosa infection and neutrophilia. We cannot
      differentiate whether this is a cause or the effect of P. aeruginosa infection,
      but propose that the level of expression of these genes may be a marker for
      susceptibility to early acquisition of P. aeruginosa in children with CF.

PMID- 22860095
TI  - Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase
      activities in cell division, autolysis, and biofilm formation.
AB  - The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a
      bifunctional enzyme that undergoes proteolytic cleavage to yield two
      catalytically active proteins, an amidase (AM) and a glucosaminidase (GL).
      Although the bifunctional nature of AtlA has long been recognized, most studies
      have focused on the combined functions of this protein in cell wall metabolism
      and biofilm development. In this study, we generated mutant derivatives of the
      clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains
      of AtlA have been deleted. Examination of these strains revealed that each mutant
      exhibited growth rates comparable to the parental strain, but showed clumping
      phenotypes and lysis profiles that were distinct from the parental strain and
      each other, suggesting distinct roles in cell wall metabolism. Given the known
      function of autolysis in the release of genomic DNA for use as a biofilm matrix
      molecule, we also tested the mutants in biofilm assays and found both AM and GL
      necessary for biofilm development. Furthermore, the use of enzymatically inactive
      point mutations revealed that both AM and GL must be catalytically active for S.
      aureus to form a biofilm. The results of this study provide insight into the
      relative contributions of AM and GL in S. aureus and demonstrate the contribution
      of Atl-mediated lysis in biofilm development.

PMID- 22860096
TI  - The hedgehog signal induced modulation of bone morphogenetic protein signaling:
      an essential signaling relay for urinary tract morphogenesis.
AB  - BACKGROUND: Congenital diseases of the urinary tract are frequently observed in
      infants. Such diseases present a number of developmental anomalies such as
      hydroureter and hydronephrosis. Although some genetically-modified mouse models
      of growth factor signaling genes reproduce urinary phenotypes, the pathogenic
      mechanisms remain obscure. Previous studies suggest that a portion of the cells
      in the external genitalia and bladder are derived from peri-cloacal mesenchymal
      cells that receive Hedgehog (Hh) signaling in the early developmental stages. We
      hypothesized that defects in such progenitor cells, which give rise to urinary
      tract tissues, may be a cause of such diseases. METHODOLOGY/PRINCIPAL FINDINGS:
      To elucidate the pathogenic mechanisms of upper urinary tract malformations, we
      analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh(-/-) displayed
      hydroureter and hydronephrosis phenotypes and reduced expression of several
      developmental markers. In addition, we suggested that Shh modulation at an early
      embryonic stage is responsible for such phenotypes by analyzing the Shh
      conditional mutants. Tissue contribution assays of Hh-responsive cells revealed
      that peri-cloacal mesenchymal cells, which received Hh signal secreted from
      cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss
      of-functional mutants for Hh signaling revealed a correlation between Hh
      signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional
      ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell
      lineages. This system thus made it possible to analyze the primary functions of
      the growth factor signaling relay. The defective Hh-to-Bmp signaling relay
      resulted in severe urinary tract phenotypes with a decrease in the number of Hh
      responsive cells. CONCLUSIONS/SIGNIFICANCE: This study identified the essential
      embryonic stages for the pathogenesis of urinary tract phenotypes. These results
      suggested that Hh-responsive mesenchymal Bmp signaling maintains the population
      of peri-cloacal mesenchyme cells, which is essential for the development of the
      ureter and the upper urinary tract.

PMID- 22860097
TI  - p14ARF post-transcriptional regulation of nuclear cyclin D1 in MCF-7 breast
      cancer cells: discrimination between a good and bad prognosis?
AB  - As part of a cell's inherent protection against carcinogenesis, p14ARF is
      upregulated in response to hyperproliferative signalling to induce cell cycle
      arrest. This property makes p14ARF a leading candidate for cancer therapy. This
      study explores the consequences of reactivating p14ARF in breast cancer and the
      potential of targeting p14ARF in breast cancer treatment. Our results show that
      activation of the p14ARF-p53-p21-Rb pathway in the estrogen sensitive MCF-7
      breast cancer cells induces many hallmarks of senescence including a large flat
      cell morphology, multinucleation, senescence-associated-beta-gal staining, and
      rapid G1 and G2/M phase cell cycle arrest. P14ARF also induces the expression of
      the proto-oncogene cyclin D1, which is most often associated with a transition
      from G1-S phase and is highly expressed in breast cancers with poor clinical
      prognosis. In this study, siRNA knockdown of cyclin D1, p21 and p53 show p21
      plays a pivotal role in the maintenance of high cyclin D1 expression, cell cycle
      and growth arrest post-p14ARF induction. High p53 and p14ARF expression and low
      p21/cyclin D1 did not cause cell-cycle arrest. Knockdown of cyclin D1 stops
      proliferation but does not reverse senescence-associated cell growth.
      Furthermore, cyclin D1 accumulation in the nucleus post-p14ARF activation
      correlated with a rapid loss of nucleolar Ki-67 protein and inhibition of DNA
      synthesis. Latent effects of the p14ARF-induced cellular processes resulting from
      high nuclear cyclin D1 accumulation included a redistribution of Ki-67 into the
      nucleoli, aberrant nuclear growth (multinucleation), and cell proliferation.
      Lastly, downregulation of cyclin D1 through inhibition of ER abrogated latent
      recurrence. The mediation of these latent effects by continuous expression of
      p14ARF further suggests a novel mechanism whereby dysregulation of cyclin D1
      could have a double-edged effect. Our results suggest that p14ARF induced
      senescence is related to late-onset breast cancer in estrogen responsive breast
      cancers and/or the recurrence of more aggressive breast cancer post-therapy.

PMID- 22860098
TI  - Transcriptional regulation of PES1 expression by c-Jun in colon cancer.
AB  - Pescadillo is a nucleolar protein that has been suggested to be involved in
      embryonic development and ribosome biogenesis. Deregulated expression of human
      pescadillo (PES1) was described in some tumors, but its precise roles in
      tumorigenesis remains unclear. In this study, we generated three monoclonal
      antibodies recognizing PES1 with high specificity and sensitivity, with which
      PES1 expression in human colon cancer was analyzed immunohistochemically. Out of
      265 colon cancer tissues, 89 (33.6%) showed positive PES1 expression, which was
      significantly higher than in non-cancerous tissues (P<0.001). Silencing of PES1
      in colon cancer cells resulted in decreased proliferation, reduced growth of
      xenografts, and cell cycle arrest in G1 phase, indicating PES1 functions as an
      oncogene. We then explored the mechanism by which PES1 expression is controlled
      in human colon cancers and demonstrated that c-Jun, but not JunB, JunD, c-Fos, or
      mutant c-Jun, positively regulated PES1 promoter transcription activity. In
      addition, we mapped -274/-264 region of PES1 promoter as the c-Jun binding
      sequence, which was validated by chromatin immunoprecipitation and
      electrophoretic mobility shift assays. Moreover, we demonstrated a positive
      correlation between c-Jun and PES1 expression in colon cancer cells and colon
      cancer tissues. Upstream of c-Jun, it was revealed that c-Jun NH2-terminal
      kinases (JNK) is essential for controlling PES1 expression. Our study, in the
      first place, uncovers the oncogenic role of PES1 in colon cancer and elucidates
      the molecular mechanism directing PES1 expression.

PMID- 22860100
TI  - Measurement properties of questionnaires measuring continuity of care: a
      systematic review.
AB  - BACKGROUND: Continuity of care is widely acknowledged as a core value in family
      medicine. In this systematic review, we aimed to identify the instruments
      measuring continuity of care and to assess the quality of their measurement
      properties. METHODS: We did a systematic review using the PubMed, Embase and
      PsycINFO databases, with an extensive search strategy including 'continuity of
      care', 'coordination of care', 'integration of care', 'patient centered care',
      'case management' and its linguistic variations. We searched from 1995 to October
      2011 and included articles describing the development and/or evaluation of the
      measurement properties of instruments measuring one or more dimensions of
      continuity of care (1) care from the same provider who knows and follows the
      patient (personal continuity), (2) communication and cooperation between care
      providers in one care setting (team continuity), and (3) communication and
      cooperation between care providers in different care settings (cross-boundary
      continuity). We assessed the methodological quality of the measurement properties
      of each instrument using the COSMIN checklist. RESULTS: We included 24 articles
      describing the development and/or evaluation of 21 instruments. Ten instruments
      measured all three dimensions of continuity of care. Instruments were developed
      for different groups of patients or providers. For most instruments, three or
      four of the six measurement properties were assessed (mostly internal
      consistency, content validity, structural validity and construct validity). Six
      instruments scored positive on the quality of at least three of six measurement
      properties. CONCLUSIONS: Most included instruments have problems with either the
      number or quality of its assessed measurement properties or the ability to
      measure all three dimensions of continuity of care. Based on the results of this
      review, we recommend the use of one of the four most promising instruments,
      depending on the target population Diabetes Continuity of Care Questionnaire,
      Alberta Continuity of Services Scale-Mental Health, Heart Continuity of Care
      Questionnaire, and Nijmegen Continuity Questionnaire.

PMID- 22860099
TI  - Differential proteomic analysis of noncardia gastric cancer from individuals of
      northern Brazil.
AB  - Gastric cancer is the second leading cause of cancer-related death worldwide. The
      identification of new cancer biomarkers is necessary to reduce the mortality
      rates through the development of new screening assays and early diagnosis, as
      well as new target therapies. In this study, we performed a proteomic analysis of
      noncardia gastric neoplasias of individuals from Northern Brazil. The proteins
      were analyzed by two-dimensional electrophoresis and mass spectrometry. For the
      identification of differentially expressed proteins, we used statistical tests
      with bootstrapping resampling to control the type I error in the multiple
      comparison analyses. We identified 111 proteins involved in gastric
      carcinogenesis. The computational analysis revealed several proteins involved in
      the energy production processes and reinforced the Warburg effect in gastric
      cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due
      to its role in aerobic glycolysis that may contribute to the Warburg effect.
      Although we observed two up-regulated spots of ENO1 in the proteomic analysis,
      the mean expression of ENO1 was reduced in gastric tumors by western blot.
      However, mean ENO1 expression seems to increase in more invasive tumors. This
      lack of correlation between proteomic and western blot analyses may be due to the
      presence of other ENO1 spots that present a slightly reduced expression, but with
      a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by
      cellular stress to protect cells against apoptosis. In the present study, HSPB1
      presented an elevated protein and mRNA expression in a subset of gastric cancer
      samples. However, no association was observed between HSPB1 expression and
      clinicopathological characteristics. Here, we identified several possible
      biomarkers of gastric cancer in individuals from Northern Brazil. These
      biomarkers may be useful for the assessment of prognosis and stratification for
      therapy if validated in larger clinical study sets.

PMID- 22860101
TI  - Mapping paratope on antithrombotic antibody 6B4 to epitope on platelet
      glycoprotein Ibalpha via molecular dynamic simulations.
AB  - Binding of platelet receptor glycoprotein Ibalpha (GPIbalpha) to the A1 domain of
      von Willebrand factor (vWF) is a critical step in both physiologic hemostasis and
      pathologic thrombosis, for initiating platelet adhesion to subendothelium of
      blood vessels at sites of vascular injury. Gain-of-function mutations in
      GPIbalpha contribute to an abnormally high-affinity binding of platelets to vWF
      and can lead to thrombosis, an accurate complication causing heart attack and
      stroke. Of various antithrombotic monoclonal antibodies (mAbs) targeting human
      GPIbalpha, 6B4 is a potent one to inhibit the interaction between GPIbalpha and
      vWF-A1 under static and flow conditions. Mapping paratope to epitope with
      mutagenesis experiments, a traditional route in researches of these
      antithrombotic mAbs, is usually expensive and time-consuming. Here, we suggested
      a novel computational procedure, which combines with homology modeling, rigid
      body docking, free and steered molecular dynamics (MD) simulations, to identify
      key paratope residues on 6B4 and their partners on GPIbalpha, with hypothesis
      that the stable hydrogen bonds and salt bridges are the important linkers between
      paratope and epitope residues. Based on a best constructed model of 6B4 bound
      with GPIbalpha, the survival ratios and rupture times of all detected hydrogen
      bonds and salt bridges in binding site were examined via free and steered MD
      simulations and regarded as indices of thermal and mechanical stabilizations of
      the bonds, respectively. Five principal paratope residues with their partners
      were predicted with their high survival ratios and/or long rupture times of
      involved hydrogen bonds, or with their hydrogen bond stabilization indices ranked
      in top 5. Exciting, the present results were in good agreement with previous
      mutagenesis experiment data, meaning a wide application prospect of our novel
      computational procedure on researches of molecular of basis of ligand-receptor
      interactions, various antithrombotic mAbs and other antibodies as well as
      theoretically design of biomolecular drugs.

PMID- 22860102
TI  - Withaferin A synergizes the therapeutic effect of doxorubicin through ROS
      mediated autophagy in ovarian cancer.
AB  - Application of doxorubicin (Dox) for the treatment of cancer is restricted due to
      its severe side effects. We used combination strategy by combining doxorubicin
      (Dox) with withaferin A (WFA) to minimize the ill effects of Dox. Treatment of
      various epithelial ovarian cancer cell lines (A2780, A2780/CP70 and CaOV3) with
      combination of WFA and Dox (WFA/DOX) showed a time- and dose-dependent
      synergistic effect on inhibition of cell proliferation and induction of cell
      death, thus reducing the dosage requirement of Dox. Combination treatment
      resulted in a significant enhancement of ROS production resulting in immense DNA
      damage, induction of autophagy analyzed by transmission electron microscope and
      increase in expression of autophagy marker LC3B, and culminated in cell death
      analyzed by cleaved caspase 3. We validated combination therapy on tumor growth
      using an in vitro 3Dimension (3D) tumor model and the more classic in vivo
      xenograft model of ovarian cancer. Both tumor models showed a 70 to 80% reduction
      in tumor growth compared to control or animals treated with WFA or Dox alone.
      Immunohistochemical analysis of the tumor tissues from animals treated with
      WFA/Dox combination showed a significant reduction in cell proliferation and
      formation of microvessels accompanied by increased in LC3B level, cleaved caspase
      3, and DNA damage. Taken together, our data suggest that combining WFA with Dox
      decreases the dosage requirement of Dox, therefore, minimizing/eliminating the
      severe side effects associated with high doses of DOX, suggesting the application
      of this combination strategy for the treatment of ovarian and other cancers with
      no or minimum side effects.

PMID- 22860103
TI  - Fibroin and sericin from Bombyx mori silk stimulate cell migration through
      upregulation and phosphorylation of c-Jun.
AB  - Wound healing is a biological process directed to the restoration of tissue that
      has suffered an injury. An important phase of wound healing is the generation of
      a basal epithelium able to wholly replace the epidermis of the wound. A broad
      range of products derived from fibroin and sericin from Bombyx mori silk are used
      to stimulate wound healing. However, so far the molecular mechanism underlying
      this phenomenon has not been elucidated. The aim of this work was to determine
      the molecular basis underlying wound healing properties of silk proteins using a
      cell model. For this purpose, we assayed fibroin and sericin in a wound healing
      scratch assay using MDA-MB-231 and Mv1Lu cells. Both proteins stimulated cell
      migration. Furthermore, treatment with sericin and fibroin involved key factors
      of the wound healing process such as upregulation of c-Jun and c-Jun protein
      phosphorylation. Moreover, fibroin and sericin stimulated the phosphorylation of
      ERK 1/2 and JNK 1/2 kinases. All these experiments were done in the presence of
      specific inhibitors for some of the cell signalling pathways referred above. The
      obtained results revealed that MEK, JNK and PI3K pathways are involved in fibroin
      and sericin stimulated cells migration. Inhibition of these three kinases
      prevented c-Jun upregulation and phosphorylation by fibroin or sericin. Fibroin
      and sericin were tested in the human keratinocyte cell line, HaCaT, with similar
      results. Altogether, our results showed that fibroin and sericin initiate cell
      migration by activating the MEK, JNK and PI3K signalling pathways ending in c-Jun
      activation.

PMID- 22860104
TI  - Effects of niacin restriction on sirtuin and PARP responses to photodamage in
      human skin.
AB  - Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), NAD(+)-dependent
      enzymes, link cellular energy status with responses to environmental stresses.
      Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known
      etiology in skin cancer. Thus, understanding the defense mechanisms in response
      to UV, including the role of SIRTs and PARPs, may be important in developing skin
      cancer prevention strategies. Here, we report expression of the seven SIRT family
      members in human skin. SIRTs gene expressions are progressively upregulated in
      A431 epidermoid carcinoma cells (SIRTs1 and 3), actinic keratoses (SIRTs 2, 3, 5,
      6, and 7) and squamous cell carcinoma (SIRTs 1-7). Photodamage induces dynamic
      changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs.
      Specific losses of SIRT proteins occur early after photodamage followed by
      accumulation later, especially for SIRT4. Niacin restriction, which decreases
      NAD(+), the sirtuin substrate, results in an increase in acetylated proteins,
      upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT
      responses to photodamage, abrogation of PARP activation following photodamage,
      and increased sensitivity to photodamage that is completely reversed by repleting
      niacin. These data support the hypothesis that SIRTs and PARPs play important
      roles in resistance to photodamage and identify specific SIRTs that respond to
      photodamage and may be targets for skin cancer prevention.

PMID- 22860105
TI  - Yeasts acquire resistance secondary to antifungal drug treatment by adaptive
      mutagenesis.
AB  - Acquisition of resistance secondary to treatment both by microorganisms and by
      tumor cells is a major public health concern. Several species of bacteria acquire
      resistance to various antibiotics through stress-induced responses that have an
      adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been
      described when the stress is nutrient deprivation. Here, we hypothesized that
      adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as
      model organisms) would also take place in response to antifungal agents (5
      fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP), giving rise to
      resistance secondary to treatment with these agents. We have developed a
      clinically relevant model where both yeasts acquire resistance when exposed to
      these agents. Stressful lifestyle associated mutation (SLAM) experiments show
      that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC), 600 (C.
      albicans -5-FC) or 1000 (S. cerevisiae--CSP) fold higher than the spontaneous
      mutation frequency, the experimental data for C. albicans -5-FC being in
      agreement with the clinical data of acquisition of resistance secondary to
      treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs
      between spontaneous and acquired, indicating that the molecular mechanisms that
      generate them are different. Remarkably, in the acquired mutations, an ectopic
      intrachromosomal recombination with an 87% homologous gene takes place with a
      high frequency. In conclusion, we present here a clinically relevant adaptive
      mutation model that fulfils the conditions reported previously.

PMID- 22860106
TI  - Analysis of drug resistance determinants in Klebsiella pneumoniae isolates from a
      tertiary-care hospital in Beijing, China.
AB  - BACKGROUND: The rates of multidrug-resistant (MDR), extensively drug-resistant
      (XDR) and pandrug-resistant (PDR) isolates among Enterobacteriaceae isolates,
      particularly Klebsiella pneumoniae, have risen substantially worldwide.
      METHODOLOGY/PRINCIPAL FINDINGS: To better understand the molecular mechanisms of
      drug resistance in K. pneumoniae, we analyzed the drug resistance determinants
      for K. pneumoniae isolates collected from the 306 Hospital, a tertiary-care
      hospital in Beijing, China, for the period of September 1, 2010-October 31, 2011.
      Drug susceptibility testing, PCR amplification and sequencing of the drug
      resistance determinants were performed. Conjugation experiments were conducted to
      examine the natural ability of drug resistance to disseminate among
      Enterobacteriaceae strains using a sodium azide-resistant Escherichia coli J53
      strain as a recipient. Among the 223 consecutive non-repetitive K. pneumoniae
      isolates included in this study, 101 (45.3%) were extended-spectrum beta
      lactamases (ESBLs) positive. The rates of MDR, XDR, and PDR isolates were 61.4%
      (n = 137), 22.0% (n = 49), and 1.8% (n = 4), respectively. Among the tested drug
      resistance-associated genes, the following ones were detected at relatively high
      rates bla(CTX-M-10) (80, 35.9%), aacC2 (73, 32.7%), dhfr (62, 27.8%), qnrS (58,
      26.0%), aacA4 (57, 25.6%), aadA1 (56, 25.1%). Results from conjugation
      experiments indicate that many of the drug resistance genes were transmissible.
      CONCLUSIONS/SIGNIFICANCE: Our data give a "snapshot" of the complex genetic
      background responsible for drug resistance in K. pneumoniae in China and
      demonstrate that a high degree of awareness and monitoring of those drug
      resistance determinants are urgently needed in order to better control the
      emergence and transmission of drug-resistant K. pneumoniae isolates in hospital
      settings.

PMID- 22860107
TI  - Vaccination with embryonic stem cells protects against lung cancer: is a broad
      spectrum prophylactic vaccine against cancer possible?
AB  - The antigenic similarity between tumors and embryos has been appreciated for many
      years and reflects the expression of embryonic gene products by cancer cells
      and/or cancer-initiating stem cells. Taking advantage of this similarity, we have
      tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic
      stem cells (ESC). Naive C57BL/6 mice were vaccinated with ESC along with a source
      of granulocyte macrophage-colony stimulating factor (GM-CSF) in order to provide
      immunostimulatory adjuvant activity. Vaccinated mice were protected against
      subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced
      anti-tumor immunity was not due to a non-specific "allo-response" as vaccination
      with allogeneic murine embryonic fibroblasts did not protect against tumor
      outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and
      memory CD8(+) T effector responses, Th1 cytokine response, higher intratumoral
      CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio, and reduced
      myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was
      found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in
      vivo depletion of CD8(+) T lymphocytes completely abrogated the protective effect
      of vaccination. Importantly, this vaccination strategy also suppressed the
      development of lung cancer induced by the combination of carcinogen
      administration and chronic pulmonary inflammation. Further refinement of this
      novel vaccine strategy and identification of shared ESC/tumor antigens may lead
      to immunotherapeutic options for lung cancer patients and, perhaps more
      importantly, could represent a first step toward the development of prophylactic
      cancer vaccines.

PMID- 22860108
TI  - Ankle-brachial index: a simple way to predict mortality among patients on
      hemodialysis--a prospective study.
AB  - BACKGROUND: Ankle-brachial index (ABI) can access peripheral artery disease and
      predict mortality in prevalent patients on hemodialysis. However, ABI has not yet
      been tested in incident patients, who present significant mortality. Typically,
      ABI is measured by Doppler, which is not always available, limiting its use in
      most patients. We therefore hypothesized that ABI, evaluated by a simplified
      method, can predict mortality in an incident hemodialysis population.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied 119 patients with ESRD who had started
      hemodialysis three times weekly. ABI was calculated by using two oscillometric
      blood pressure devices simultaneously. Patients were followed until death or the
      end of the study. ABI was categorized in two groups normal (0.9-1.3) or abnormal
      (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months
      (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI
      abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality
      in a multiple regression analysis. CONCLUSIONS: An easy and inexpensive technique
      to measure ABI was tested and showed to be significant in predicting mortality.
      Both low and high ABI were associated to mortality in incident patients on
      hemodialysis. This technique allows nephrologists to identify high-risk patients
      and gives the opportunity of early intervention that could alter the natural
      progression of this population.

PMID- 22860109
TI  - Distinct cardiac transcriptional profiles defining pregnancy and exercise.
AB  - BACKGROUND: Although the hypertrophic responses of the heart to pregnancy and
      exercise are both considered to be physiological processes, they occur in quite
      different hormonal and temporal settings. In this study, we have compared the
      global transcriptional profiles of left ventricular tissues at various time
      points during the progression of hypertrophy in exercise and pregnancy.
      METHODOLOGY/PRINCIPAL FINDINGS: The following groups of female mice were
      analyzed: non-pregnant diestrus cycle sedentary control, mid-pregnant, late
      pregnant, and immediate-postpartum, and animals subjected to 7 and 21 days of
      voluntary wheel running. Hierarchical clustering analysis shows that while mid
      pregnancy and both exercise groups share the closest relationship and similar
      gene ontology categories, late pregnancy and immediate post-partum are quite
      different with high representation of secreted/extracellular matrix-related
      genes. Moreover, pathway-oriented ontological analysis shows that metabolism
      regulated by cytochrome P450 and chemokine pathways are the most significant
      signaling pathways regulated in late pregnancy and immediate-postpartum,
      respectively. Finally, increases in expression of components of the proteasome
      observed in both mid-pregnancy and immediate-postpartum also result in enhanced
      proteasome activity. Interestingly, the gene expression profiles did not
      correlate with the degree of cardiac hypertrophy observed in the animal groups,
      suggesting that distinct pathways are employed to achieve similar amounts of
      cardiac hypertrophy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that
      cardiac adaptation to the later stages of pregnancy is quite distinct from both
      mid-pregnancy and exercise. Furthermore, it is very dynamic since, by 12 hours
      post-partum, the heart has already initiated regression of cardiac growth, and 50
      genes have changed expression significantly in the immediate-postpartum compared
      to late-pregnancy. Thus, pregnancy-induced cardiac hypertrophy is a more complex
      process than exercise-induced cardiac hypertrophy and our data suggest that the
      mechanisms underlying the two types of hypertrophy have limited overlap.

PMID- 22860110
TI  - The impact of B-cell perturbations on pneumococcal conjugate vaccine response in
      HIV-infected adults.
AB  - Untreated HIV infection results in severe perturbations of the B-cell population
      and hyporesponsiveness to vaccination. We studied associations between
      circulating B-cell subsets and antibody response to pneumococcal conjugate
      vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults
      were grouped according to antiretroviral therapy (ART) and CD4+ cell count as
      follows: 20 ART-naive (no prior ART), 62 ART-responders (received ART, and CD4
      count >500 cells/ul), and 13 impaired responders (received ART for more than 3
      years, and CD4 count <500 cells/ul). All subjects were immunized twice with
      double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909
      (toll-like receptor 9 agonist) at baseline and after three months. Pre
      vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG
      concentrations for vaccine serotypes were quantified by ELISA at baseline and 3,
      4, and 9 months post-vaccination. ART responders had more isotype-switched memory
      B cells and more marginal-zone (MZ)-like B cells compared with impaired
      responders. Furthermore, ART-naive patients had higher concentration of
      transitional B cells and plasmablasts compared with B cells of other patient
      groups. The concentration of MZ-like, isotype switched memory cells and
      plasmablasts correlated positively with post-vaccination IgG concentration at 3,
      4, and 9 months. Low concentrations of isotype-switched memory B cells was the
      strongest independent predictor of poor pneumococcal conjugate vaccine
      responsiveness, emphasizing that B-cell subset disturbances are associated with
      poor vaccine response among HIV-infected patients.

PMID- 22860111
TI  - Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.
AB  - Neuroligins (Nlgns) are postsynaptic, integral membrane cell adhesion molecules
      that play important roles in the formation, validation, and maturation of
      synapses in the mammalian central nervous system. Given their prominent roles in
      the life cycle of synapses, it might be expected that the loss of neuroligin
      family members would affect the stability of synaptic organization, and
      ultimately, affect the tenacity and persistence of individual synaptic junctions.
      Here we examined whether and to what extent the loss of Nlgn-1 affects the
      dynamics of several key synaptic molecules and the constancy of their contents at
      individual synapses over time. Fluorescently tagged versions of the postsynaptic
      scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the
      presynaptic vesicle molecule SV2A were expressed in primary cortical cultures
      from Nlgn-1 KO mice and wild-type (WT) littermates, and live imaging was used to
      follow the constancy of their contents at individual synapses over periods of 8
      12 hours. We found that the loss of Nlgn-1 was associated with larger
      fluctuations in the synaptic contents of these molecules and a poorer
      preservation of their contents at individual synapses. Furthermore, rates of
      synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice.
      Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1
      knockout mice were negated by suppressing spontaneous network activity. These
      findings suggest that the loss of Nlgn-1 is associated with some use-dependent
      destabilization of excitatory synapse organization, and indicate that in the
      absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat
      impaired.

PMID- 22860112
TI  - Allele copy number and underlying pathology are associated with subclinical
      severity in equine type 1 polysaccharide storage myopathy (PSSM1).
AB  - Equine type 1 polysaccharide storage myopathy (PSSM1), a common glycogenosis
      associated with an R309H founder mutation in the glycogen synthase 1 gene (GYS1),
      shares pathological features with several human myopathies. In common with
      related human disorders, the pathogenesis remains unclear in particular, the
      marked phenotypic variability between affected animals. Given that affected
      animals accumulate glycogen and alpha-crystalline polysaccharide within their
      muscles, it is possible that physical disruption associated with the presence of
      this material could exacerbate the phenotype. The aim of this study was to
      compare the histopathological changes in horses with PSSM1, and specifically, to
      investigate the hypothesis that the severity of underlying pathology, (e.g.
      vacuolation and inclusion formation) would (1) be higher in homozygotes than
      heterozygotes and (2) correlate with clinical severity. Resting and post-exercise
      plasma creatine kinase (CK) and aspartate aminotransferase (AST) enzyme activity
      measurements and muscle pathology were assessed in matched cohorts of PSSM1
      homozygotes, heterozygotes or control horses. Median (interquartile range (IR))
      resting CK activities were 364 (332-764) U/L for homozygotes, 301 (222-377) U/L
      for heterozygotes and 260 (216-320) U/L for controls, and mean (+/- SD) AST
      activity for homozygotes were 502 (+/116) U/L, for heterozygotes, 357 (+/-92) U/L
      and for controls, 311 (+/-64) U/L and were significantly different between groups
      (P = 0.04 and P = 0.01 respectively). Resting plasma AST activity was
      significantly associated with the severity of subsarcolemmal vacuolation (rho =
      0.816; P = 0.01) and cytoplasmic inclusions (rho = 0.766; P = 0.01). There were
      fewer type 2* and more type 2a muscle fibres in PSSM1-affected horses. Our
      results indicate that PSSM1 has incomplete dominance. Furthermore, the
      association between plasma muscle enzyme activity and severity of underlying
      pathology suggests that physical disruption of myofibres may contribute to the
      myopathic phenotype. This work provides insight into PSSM1 pathogenesis and has
      implications for related human glycogenoses.

PMID- 22860113
TI  - Serum levels of choline-containing compounds are associated with aerobic fitness
      level: the HUNT-study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death worldwide,
      and the number of people at risk is continuously growing. New methods for early
      risk prediction are therefore needed to actuate prevention strategies before the
      individuals are diagnosed with CVD. Several studies report that aerobic fitness
      level, measured as maximal oxygen uptake (VO(2max)), is the single best predictor
      of future CVD mortality in healthy people. Based on this, we wanted to study
      differences between healthy individuals with a large difference in VO(2max)-level
      to identify new biomarkers of low aerobic fitness that may also have potential as
      early biomarkers of CVD risk. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from
      218 healthy individuals with a low VO(2max) (n = 108, 63 women) or high VO(2max)
      (n = 110, 64 women) were analysed with MR metabolomics. In addition, standard
      clinical-chemical analyses for glucose, lipids, liver enzymes, micro-CRP, and
      colorimetric analysis on circulating choline were performed. Individuals in the
      low VO(2max)-group had increased serum levels of free choline, decreased
      phosphatidylcholine, increased glucose and decreased unsaturated fatty acids
      compared to the individuals in the high VO(2max)-group. CONCLUSIONS/SIGNIFICANCE:
      Aerobic fitness dependent differences in serum levels of free choline and
      phosphatidylcholine are observed. They should be further studied as potential
      early markers of CVD risk.

PMID- 22860114
TI  - Pituitary-specific overexpression of porcine follicle-stimulating hormone leads
      to improvement of female fecundity in BAC transgenic mice.
AB  - Follicle-stimulating hormone (FSH) is a pituitary glycoprotein that, together
      with luteinizing hormone, plays a crucial role in ovarian folliculogenesis and
      female fertility. We previously found that FSH beta is a major gene controlling
      high prolificacy of Chinese Erhualian pigs. To directly study the biological
      effects on reproductive function of porcine FSH (pFSH) for polyovulatory species,
      we generated a novel gain-of-function mouse model using a bacterial artificial
      chromosome (BAC) system to jointly introduce 92 kb and 165 kb genomic fragments
      comprising the pFSH alpha- and beta-subunit genes. These directed the
      physiological expression of pFSH with the same temporal and spatial pattern as
      endogenous FSH in female transgenic (TG) mice. Serum levels of biologically
      active pFSH heterodimers in independent TG lines ranged from 6.36 to 19.83 IU/L.
      High basal pFSH activity led to a significant reduction of serum LH and
      testosterone levels in TG females compared to wild-type (WT) littermates, yet
      endogenous FSH and estradiol levels were significantly elevated. Interestingly,
      ovarian histology showed that the number of corpora lutea was significantly
      higher at 14 and 28 weeks of age in TG females and breeding curves revealed that
      mean litter sizes of TG females were obviously larger than for WT littermates
      before 52 weeks of age. These findings indicate that pituitary-specific
      overexpression of pFSH within physiological boundaries can increase ovulation
      rate and litter size, but it does not cause reproductive defects. Therefore, our
      TG mouse model provides exciting insights for investigating the actions of pFSH
      in vivo.

PMID- 22860115
TI  - Eukaryotic translation elongation factor 1A (eEF1A) domain I from S. cerevisiae
      is required but not sufficient for inter-species complementation.
AB  - Ethanolamine phosphoglycerol (EPG) is a protein modification attached exclusively
      to eukaryotic elongation factor 1A (eEF1A). In mammals and plants, EPG is linked
      to conserved glutamate residues located in eEF1A domains II and III, whereas in
      the unicellular eukaryote Trypanosoma brucei, only domain III is modified by a
      single EPG. A biosynthetic precursor of EPG and structural requirements for EPG
      attachment to T. brucei eEF1A have been reported, but nothing is known about the
      EPG modifying enzyme(s). By expressing human eEF1A in T. brucei, we now show that
      EPG attachment to eEF1A is evolutionarily conserved between T. brucei and Homo
      sapiens. In contrast, S. cerevisiae eEF1A, which has been shown to lack EPG is
      not modified in T. brucei. Furthermore, we show that eEF1A cannot functionally
      complement across species when using T. brucei and S. cerevisiae as model
      organisms. However, functional complementation in yeast can be obtained using
      eEF1A chimera containing domains II or III from other species. In contrast, yeast
      domain I is strictly required for functional complementation in S. cerevisiae.

PMID- 22860116
TI  - Cell surface estrogen receptor alpha is upregulated during subchronic metabolic
      stress and inhibits neuronal cell degeneration.
AB  - In addition to the classical nuclear estrogen receptor, the expression of non
      nuclear estrogen receptors localized to the cell surface membrane (mER) has
      recently been demonstrated. Estrogen and its receptors have been implicated in
      the development or progression of numerous neurodegenerative disorders.
      Furthermore, the pathogenesis of these diseases has been associated with
      disturbances of two key cellular programs: apoptosis and autophagy. An excess of
      apoptosis or a defect in autophagy has been implicated in neurodegeneration. The
      aim of this study was to clarify the role of ER in determining neuronal cell fate
      and the possible implication of these receptors in regulating either apoptosis or
      autophagy. The human neuronal cell line SH-SY5Y and mouse neuronal cells in
      primary culture were thus exposed to chronic minimal peroxide treatment (CMP), a
      form of subcytotoxic minimal chronic stress previously that mimics multiple
      aspects of long-term cell stress and represents a limited molecular proxy for
      neurodegenerative processes. We actually found that either E2 or E2-bovine serum
      albumin construct (E2BSA, i.e. a non-permeant form of E2) was capable of
      modulating intracellular cell signals and regulating cell survival and death. In
      particular, under CMP, the up-regulation of mERalpha, but not mERbeta, was
      associated with functional signals (ERK phosphorylation and p38
      dephosphorylation) compatible with autophagic cytoprotection triggering and
      leading to cell survival. The mERalpha trafficking appeared to be independent of
      the microfilament system cytoskeletal network but was seemingly associated with
      microtubular apparatus network, i.e., to MAP2 molecular chaperone. Importantly,
      antioxidant treatments, administration of siRNA to ERalpha, or the presence of
      antagonist of ERalpha hindered these events. These results support that the
      surface expression of mERalpha plays a pivotal role in determining cell fate, and
      that ligand-induced activation of mER signalling exerts a powerful cell-survival
      signal. These results shed new light on the pathogenetic mechanisms leading to
      neuronal cell degeneration.

PMID- 22860117
TI  - Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman
      primates.
AB  - Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed
      live-virus vaccine is associated with serious health risks, making its general
      usage unacceptable. Attenuated vaccines are being developed as alternatives, the
      most advanced of which is modified-vaccinia virus Ankara (MVA). We previously
      developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus
      antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates
      from lethal orthopoxvirus disease. Here, we investigated the capacity of the
      molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to
      enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly
      increased protective antibody responses in mice. We directly compared the 4pox
      plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP)
      challenge model. NHPs were vaccinated twice with MVA by intramuscular injection
      or the 4pox/LT vaccine delivered using a disposable gene gun device. As a
      positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each
      vaccine developed anti-orthopoxvirus antibody responses, including those against
      the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed
      severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs
      vaccinated with MVA were protected from lethality, but three of five developed
      severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT
      survived and only one developed severe disease. None of the 4pox/LT-vaccinated
      animals shed virus. Our findings show, for the first time, that a subunit
      orthopoxvirus vaccine delivered by the same schedule can provide a degree of
      protection at least as high as that of MVA.

PMID- 22860118
TI  - Sialoglycosylation of RBC in visceral leishmaniasis leads to enhanced oxidative
      stress, calpain-induced fragmentation of spectrin and hemolysis.
AB  - Visceral leishmaniasis (VL) caused by the intracellular parasite Leishmania
      donovani accounts for an estimated 12 million cases of human infection. It is
      almost always associated with anemia, which severely complicates the disease
      course. However, the pathological processes leading to anemia in VL have thus far
      not been adequately characterized to date. In studying the glycosylation patterns
      of peripheral blood cells we found that the red blood cells (RBC) of VL patients
      (RBC(VL)) express eight 9-O-acetylated sialoglycoproteins (9-O-AcSGPs) that are
      not detected in the RBC of healthy individuals (RBC(N)). At the same time, the
      patients had high titers of anti-9-O-AcSGP IgG antibodies in their sera. These
      two conditions appear to be linked and related to the anemic state of the
      patients, as exposure of RBC(VL) but not RBC(N) to anti-9-O-AcSGPs antibodies
      purified from patient sera triggered a series of responses. These included
      calcium influx via the P/Q-type but not L-type channels, activation of calpain I,
      proteolysis of spectrin, enhanced oxidative stress, lipid peroxidation,
      externalization of phosphatidyl serine with enhanced erythrophagocytosis,
      enhanced membrane fragility and, finally, hemolysis. Taken together, this study
      suggests that the enhanced hemolysis is linked to an impairment of membrane
      integrity in RBC(VL) which is mediated by ligand-specific interaction of surface
      9-O-AcSGPs. This affords a potential explanation for the structural and
      functional features of RBC(VL) which are involved in the hemolysis related to the
      anemia which develops in VL patients.

PMID- 22860119
TI  - Identification of rat ventral tegmental area GABAergic neurons.
AB  - The canonical two neuron model of opioid reward posits that mu opioid receptor
      (MOR) activation produces reward by disinhibiting midbrain ventral tegmental area
      (VTA) dopamine neurons through inhibition of local GABAergic interneurons.
      Although indirect evidence supports the neural circuit postulated by this model,
      its validity has been called into question by growing evidence for VTA neuronal
      heterogeneity and the recent demonstration that MOR agonists inhibit GABAergic
      terminals in the VTA arising from extrinsic neurons. In addition, VTA MOR reward
      can be dopamine-independent. To directly test the assumption that MOR activation
      directly inhibits local GABAergic neurons, we investigated the properties of rat
      VTA GABA neurons directly identified with either immunocytochemistry for GABA or
      GAD65/67, or in situ hybridization for GAD65/67 mRNA. Utilizing co-labeling with
      an antibody for the neural marker NeuN and in situ hybridization against
      GAD65/67, we found that 23+/-3% of VTA neurons are GAD65/67(+). In contrast to
      the assumptions of the two neuron model, VTA GABAergic neurons are heterogeneous,
      both physiologically and pharmacologically. Importantly, only 7/13 confirmed VTA
      GABA neurons were inhibited by the MOR selective agonist DAMGO. Interestingly,
      all confirmed VTA GABA neurons were insensitive to the GABA(B) receptor agonist
      baclofen (0/6 inhibited), while all confirmed dopamine neurons were inhibited
      (19/19). The heterogeneity of opioid responses we found in VTA GABAergic neurons,
      and the fact that GABA terminals arising from neurons outside the VTA are
      inhibited by MOR agonists, make further studies essential to determine the local
      circuit mechanisms underlying VTA MOR reward.

PMID- 22860120
TI  - Derivation of corneal endothelial cell-like cells from rat neural crest cells in
      vitro.
AB  - The aim of this study was to investigate the feasibility of inducing rat neural
      crest cells (NCC) to differentiate to functional corneal endothelial cell (CEC)
      like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned
      medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used
      to detect expression of the corneal endothelium differentiation marker N-cadherin
      and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were
      transplanted to the corneal endothelium of a rat corneal endothelium deficiency
      model, and an eye-down position was maintained for 24 hours to allow cell
      attachment. The animals were observed for as long as 2 months after surgery and
      underwent clinical and histological examination. Spindle-like NCC turned to
      polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula
      occludens-1 and sodium-potassium pump Na(+)/K(+) ATPase. The corneas of the
      experimental group were much clearer than those of the control group and the mean
      corneal thickness in the experimental group was significantly less than in the
      control group7, 14, 21 and 28 days after surgery. Confocal microscopy through
      focusing and histological analysis confirmed that green fluorescence-positive CEC
      like cells formed a monolayer covering the Descemet's membrane in the
      experimental group. In conclusion, CEC-like cells derived from NCCs displayed
      characters of native CEC, and the induction protocol provides guidance for future
      human CEC induction from NCC.

PMID- 22860121
TI  - Identification of 34 novel proinflammatory proteins in a genome-wide macrophage
      functional screen.
AB  - Signal transduction pathways activated by Toll-like Receptors and the IL-1 family
      of cytokines are fundamental to mounting an innate immune response and thus to
      clearing pathogens and promoting wound healing. Whilst mechanistic understanding
      of the regulation of innate signalling pathways has advanced considerably in
      recent years, there are still a number of critical controllers to be discovered.
      In order to characterise novel regulators of macrophage inflammation, we have
      carried out an extensive, cDNA-based forward genetic screen and identified 34
      novel activators, based on their ability to induce the expression of cxcl2. Many
      are physiologically expressed in macrophages, although the majority of genes
      uncovered in our screen have not previously been linked to innate immunity. We
      show that expression of particular activators has profound but distinct impacts
      on LPS-induced inflammatory gene expression, including switch-type, amplifier and
      sensitiser behaviours. Furthermore, the novel genes identified here interact with
      the canonical inflammatory signalling network via specific mechanisms, as
      demonstrated by the use of dominant negative forms of IL1/TLR signalling
      mediators.

PMID- 22860122
TI  - Aciculatin inhibits granulocyte colony-stimulating factor production by human
      interleukin 1beta-stimulated fibroblast-like synoviocytes.
AB  - The expression of granulocyte colony-stimulating factor (G-CSF), the major
      regulator of neutrophil maturation, by human fibroblast-like synoviocytes (FLS)
      can be stimulated by the inflammatory cytokine interleukin-1beta (IL-1beta). G
      CSF is known to contribute to the pathologic processes of destructive arthritis,
      but the induction mechanism remains unknown. The aims of this study were to
      identify the signaling pathways involved in IL-1beta-stimulated G-CSF production
      and to determine whether this process was inhibited by aciculatin (8
      ((2R,4S,5S,6R)-tetrahydro-4,5-dihydroxy-6-methyl-2H-pyran-2-yl)-5-hydroxy-2-(4
      hydroxyphenyl)-7-methoxy-4H-chromen-4-one), the major bioactive component of
      Chrysopogon aciculatus. IL-1beta-induced cytokine expression was evaluated by
      measuring mRNA and protein levels by RT-PCR, ELISA, and Milliplex(r) assay.
      Whether aciculatin inhibited IL-1beta-stimulated G-CSF expression, and if so,
      how, were evaluated using western blot assay, an electrophoretic mobility shift
      assay, and a reporter gene assay. Neutrophil differentiation was determined by
      Wright-Giemsa staining and flow cytometry. Aciculatin markedly inhibited G-CSF
      expression induced by IL-1beta (10 ng/mL) in a concentration-dependent manner (1
      10 uM). In clarifying the mechanisms involved, aciculatin was found to inhibit
      the IL-1beta-induced activation of the IkappaB kinase (IKK)/IkappaB/nuclear
      factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways by
      suppressing the DNA binding activity of the transcription factors NF-kappaB and
      activator protein (AP)-1. Furthermore, aciculatin significantly inhibited the G
      CSF-mediated phosphorylation of Janus kinase-signal transducer and activator of
      transcription (JAK-STAT) and Akt and neutrophil differentiation from precursor
      cells. Our results show that aciculatin inhibits IL-1beta-stimulated G-CSF
      expression and the subsequent neutrophil differentiation, suggesting that it
      might have therapeutic potential for inflammatory arthritis.

PMID- 22860123
TI  - Endocannabinoids measurement in human saliva as potential biomarker of obesity.
AB  - BACKGROUND: The discovery of the endocannabinoid system and of its role in the
      regulation of energy balance has significantly advanced our understanding of the
      physiopathological mechanisms leading to obesity and type 2 diabetes. New
      knowledge on the role of this system in humans has been acquired by measuring
      blood endocannabinoids. Here we explored endocannabinoids and related N
      acylethanolamines in saliva and verified their changes in relation to body weight
      status and in response to a meal or to body weight loss. METHODOLOGY/PRINCIPAL
      FINDINGS: Fasting plasma and salivary endocannabinoids and N-acylethanolamines
      were measured through liquid mass spectrometry in 12 normal weight and 12 obese,
      insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines
      were evaluated in the same cohort before and after the consumption of a meal.
      Changes in salivary endocannabinoids and N-acylethanolamines after body weight
      loss were investigated in a second group of 12 obese subjects following a 12
      weeks lifestyle intervention program. The levels of mRNAs coding for enzymes
      regulating the metabolism of endocannabinoids, N-acylethanolamines and of
      cannabinoid type 1 (CB(1)) receptor, alongside endocannabinoids and N
      acylethanolamines content, were assessed in human salivary glands. The
      endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide
      (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and
      palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were
      significantly higher in obese than in normal weight subjects. Fasting salivary
      AEA and OEA directly correlated with BMI, waist circumference and fasting
      insulin. Salivary endocannabinoids and N-acylethanolamines did not change in
      response to a meal. CB(1) receptors, ligands and enzymes were expressed in the
      salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks
      lifestyle program significantly decreased salivary AEA levels.
      CONCLUSIONS/SIGNIFICANCE: Endocannabinoids and N-acylethanolamines are
      quantifiable in saliva and their levels correlate with obesity but not with
      feeding status. Body weight loss significantly decreases salivary AEA, which
      might represent a useful biomarker in obesity.

PMID- 22860124
TI  - Evaluating cellular polyfunctionality with a novel polyfunctionality index.
AB  - Functional evaluation of naturally occurring or vaccination-induced T cell
      responses in mice, men and monkeys has in recent years advanced from single
      parameter (e.g. IFN-gamma-secretion) to much more complex multidimensional
      measurements. Co-secretion of multiple functional molecules (such as cytokines
      and chemokines) at the single-cell level is now measurable due primarily to major
      advances in multiparametric flow cytometry. The very extensive and complex
      datasets generated by this technology raise the demand for proper analytical
      tools that enable the analysis of combinatorial functional properties of T cells,
      hence polyfunctionality. Presently, multidimensional functional measures are
      analysed either by evaluating all combinations of parameters individually or by
      summing frequencies of combinations that include the same number of simultaneous
      functions. Often these evaluations are visualized as pie charts. Whereas pie
      charts effectively represent and compare average polyfunctionality profiles of
      particular T cell subsets or patient groups, they do not document the degree or
      variation of polyfunctionality within a group nor does it allow more
      sophisticated statistical analysis. Here we propose a novel polyfunctionality
      index that numerically evaluates the degree and variation of polyfuntionality,
      and enable comparative and correlative parametric and non-parametric statistical
      tests. Moreover, it allows the usage of more advanced statistical approaches,
      such as cluster analysis. We believe that the polyfunctionality index will render
      polyfunctionality an appropriate end-point measure in future studies of T cell
      responsiveness.

PMID- 22860125
TI  - Comparative transcriptional analysis of clinically relevant heat stress response
      in Clostridium difficile strain 630.
AB  - Clostridium difficile is considered to be one of the most important causes of
      health care-associated infections worldwide. In order to understand more fully
      the adaptive response of the organism to stressful conditions, we examined
      transcriptional changes resulting from a clinically relevant heat stress (41 
      degrees C versus 37  degrees C) in C. difficile strain 630 and identified 341
      differentially expressed genes encompassing multiple cellular functional
      categories. While the transcriptome was relatively resilient to the applied heat
      stress, we noted upregulation of classical heat shock genes including the groEL
      and dnaK operons in addition to other stress-responsive genes. Interestingly, the
      flagellin gene (fliC) was downregulated, yet genes encoding the cell-wall
      associated flagellar components were upregulated suggesting that while motility
      may be reduced, adherence--to mucus or epithelial cells--could be enhanced during
      infection. We also observed that a number of phage associated genes were
      downregulated, as were genes associated with the conjugative transposon Tn5397
      including a group II intron, thus highlighting a potential decrease in
      retromobility during heat stress. These data suggest that maintenance of lysogeny
      and genome wide stabilisation of mobile elements could be a global response to
      heat stress in this pathogen.

PMID- 22860126
TI  - Taking a comparative approach: analysing personality as a multivariate
      behavioural response across species.
AB  - Animal personality, repeatable behaviour through time and across contexts, is
      ecologically and evolutionarily important as it can account for the exhibition of
      sub-optimal behaviours. Interspecific comparisons have been suggested as
      important for understanding the evolution of animal personality; however, these
      are seldom accomplished due, in part, to the lack of statistical tools for
      quantifying differences and similarities in behaviour between groups of
      individuals. We used nine species of closely-related coral reef fishes to
      investigate the usefulness of ecological community analyses for the analysis of
      between-species behavioural differences and behavioural heterogeneity. We first
      documented behavioural carryover across species by observing the fishes'
      behaviour and measuring their response to a threatening stimulus to quantify
      boldness. Bold fish spent more time away from the reef and fed more than shy
      fish. We then used ecological community analysis tools (canonical variate
      analysis, multi-response permutation procedure, and permutational analysis of
      multivariate dispersion) and identified four 'clusters' of behaviourally similar
      fishes, and found that the species differ in the behavioural variation expressed;
      some species are more behaviourally heterogeneous than others. We found that
      ecological community analysis tools are easily and fruitfully applied to
      comparative studies of personality and encourage their use by future studies.

PMID- 22860127
TI  - Genomic characterization of Listeria monocytogenes strains involved in a
      multistate listeriosis outbreak associated with cantaloupe in US.
AB  - A multistate listeriosis outbreak associated with cantaloupe consumption was
      reported in the United States in September, 2011. The outbreak investigation
      recorded a total of 146 invasive illnesses, 30 deaths and one miscarriage.
      Subtyping of the outbreak associated clinical, food and environmental isolates
      revealed two serotypes (1/2a and 1/2b) and four pulsed-field gel electrophoresis
      two-enzyme pattern combinations I, II, III, and IV, including one rarely seen
      before this outbreak. A DNA-microarray, Listeria GeneChip(r), developed by FDA
      from 24 Listeria monocytogenes genome sequences, was used to further characterize
      a representative sample of the outbreak isolates. The microarray data (in the
      form of present or absent calls of specific DNA sequences) separated the isolates
      into two distinct groups as per their serotypes. The gene content of the outbreak
      associated isolates was distinct from that of the previously-reported outbreak
      strains belonging to the same serotypes. Although the 1/2b outbreak associated
      isolates are closely related to each other, the 1/2a isolates could be further
      divided into two distinct genomic groups, one represented by pattern combination
      I strains and the other represented by highly similar pattern combinations III
      and IV strains. Gene content analysis of these groups revealed unique genomic
      sequences associated with these two 1/2a genovars. This work underscores the
      utility of multiple approaches, such as serotyping, PFGE and DNA microarray
      analysis to characterize the composition of complex polyclonal listeriosis
      outbreaks.

PMID- 22860128
TI  - Hexokinase 2, glycogen synthase and phosphorylase play a key role in muscle
      glycogen supercompensation.
AB  - BACKGROUND: Glycogen-depleting exercise can lead to supercompensation of muscle
      glycogen stores, but the biochemical mechanisms of this phenomenon are still not
      completely understood. METHODS: Using chronic low-frequency stimulation (CLFS) as
      an exercise model, the tibialis anterior muscle of rabbits was stimulated for
      either 1 or 24 hours, inducing a reduction in glycogen of 90% and 50%
      respectively. Glycogen recovery was subsequently monitored during 24 hours of
      rest. RESULTS: In muscles stimulated for 1 hour, glycogen recovered basal levels
      during the rest period. However, in those stimulated for 24 hours, glycogen was
      supercompensated and its levels remained 50% higher than basal levels after 6
      hours of rest, although the newly synthesized glycogen had fewer branches. This
      increase in glycogen correlated with an increase in hexokinase-2 expression and
      activity, a reduction in the glycogen phosphorylase activity ratio and an
      increase in the glycogen synthase activity ratio, due to dephosphorylation of
      site 3a, even in the presence of elevated glycogen stores. During
      supercompensation there was also an increase in 5'-AMP-activated protein kinase
      phosphorylation, correlating with a stable reduction in ATP and total purine
      nucleotide levels. CONCLUSIONS: Glycogen supercompensation requires a coordinated
      chain of events at two levels in the context of decreased cell energy balance:
      First, an increase in the glucose phosphorylation capacity of the muscle and
      secondly, control of the enzymes directly involved in the synthesis and
      degradation of the glycogen molecule. However, supercompensated glycogen has
      fewer branches.

PMID- 22860129
TI  - Analysis of genes expression of Spodoptera exigua larvae upon AcMNPV infection.
AB  - BACKGROUND: The impact of Autographa californica multicapsid nucleopolyhedrovirus
      (AcMNPV) infection on host gene expression in Spodoptera exigua 4th instar larvae
      was investigated through the use of 454 sequencing-based RNA-seq of cDNA
      libraries developed from insects challenged with active AcMNPV or heat
      inactivated AcMNPV. METHODOLOGY/PRINCIPAL FINDINGS: By comparing the two cDNA
      libraries, we show that 201 host genes are significantly up-regulated and 234
      genes are significantly down-regulated by active AcMNPV infection. Down-regulated
      host genes included genes encoding antimicrobial peptides, namely three gloverin
      isoforms and an attacin, indicating that the viral infection actively repressed
      the expression of a portion of the host immune gene repertoire. Another
      interesting group of down-regulated host genes included genes encoding two
      juvenile hormone binding proteins and a hexamerin, all of which are involved in
      juvenile hormone regulation. The expression of these genes was enhanced by the
      topical application of Juvenile Hormone III (JHIII) in the insects challenged
      with heat-inactivated AcMNPV. However, infection with the active virus strongly
      suppresses the expression of these three genes, regardless of the absence or
      presence of JHIII. CONCLUSIONS/SIGNIFICANCE: Using RNA-seq, we have identified
      groups of immune-regulated and juvenile hormone-regulated genes that are
      suppressed by infection with active AcMNPV. This information and further studies
      on the regulation of host gene expression by AcMNPV will provide the tools needed
      to enhance the utility of the virus as an effective protein expression system and
      as an insecticide.

PMID- 22860130
TI  - Longitudinal MRI study on the natural history of carotid artery plaques in
      symptomatic patients.
AB  - PURPOSE: To investigate the natural history of carotid atherosclerosis in
      patients who experienced a TIA or ischemic stroke. PATIENTS AND METHODS: Ninety
      two TIA/stroke patients (57 men, mean age 67.7 +/- 9.8 years) with ipsilateral
      <70% carotid stenosis underwent multisequence MRI of the plaque ipsilateral to
      the symptomatic side at baseline and after one year. For each plaque, several
      parameters were assessed at both time points. RESULTS: Carotid lumen, wall and
      total vessel ( = carotid lumen and wall) volume did not significantly change.
      Forty-four patients had a plaque with a lipid-rich necrotic core (LRNC) at
      baseline, of which 34 also had a LRNC after one year. In three patients a LRNC
      appeared after one year. Thirty patients had a plaque with a thin and/or ruptured
      fibrous cap (FC) at both time points. In seven patients, FC status changed from
      thin and/or ruptured into thick and intact. In three patients, FC status changed
      from thick and intact into thin and/or ruptured. Twenty patients had intraplaque
      hemorrhage (IPH) at both time points. In four patients, IPH disappeared, whereas
      in three patients, new IPH appeared at follow-up. CONCLUSION: In TIA/stroke
      patients, carotid plaque morphology does not significantly change over a one-year
      period. IPH and FC status change in a minority of patients.

PMID- 22860131
TI  - Crystal structures of the network-forming short-arm tips of the laminin beta1 and
      gamma1 chains.
AB  - The heterotrimeric laminins are a defining component of basement membranes and
      essential for tissue formation and function in all animals. The three short arms
      of the cross-shaped laminin molecule are composed of one chain each and their
      tips mediate the formation of a polymeric network. The structural basis for
      laminin polymerisation is unknown. We have determined crystal structures of the
      short-arm tips of the mouse laminin beta1 and gamma1 chains, which are grossly
      similar to the previously determined structure of the corresponding alpha5 chain
      region. The short-arm tips consist of a laminin N-terminal (LN) domain that is
      attached like the head of a flower to a rod-like stem formed by tandem laminin
      type epidermal growth factor-like (LE) domains. The LN domain is a beta-sandwich
      with elaborate loop regions that differ between chains. The gamma1 LN domain
      uniquely contains a calcium binding site. The LE domains have little regular
      structure and are stabilised by cysteines that are disulphide-linked 1-3, 2-4, 5
      6 and 7-8 in all chains. The LN surface is not conserved across the alpha, beta
      and gamma chains, but within each chain subfamily there is a striking
      concentration of conserved residues on one face of the beta-sandwich, while the
      opposite face invariably is shielded by glycans. We propose that the extensive
      conserved patches on the beta and gamma LN domains mediate the binding of these
      two chains to each other, and that the alpha chain LN domain subsequently binds
      to the composite beta-gamma surface. Mutations in the laminin beta2 LN domain
      causing Pierson syndrome are likely to impair the folding of the beta2 chain or
      its ability to form network interactions.

PMID- 22860132
TI  - Interspecies avian brain chimeras reveal that large brain size differences are
      influenced by cell-interdependent processes.
AB  - Like humans, birds that exhibit vocal learning have relatively delayed
      telencephalon maturation, resulting in a disproportionately smaller brain
      prenatally but enlarged telencephalon in adulthood relative to vocal non-learning
      birds. To determine if this size difference results from evolutionary changes in
      cell-autonomous or cell-interdependent developmental processes, we transplanted
      telencephala from zebra finch donors (a vocal-learning species) into Japanese
      quail hosts (a vocal non-learning species) during the early neural tube stage
      (day 2 of incubation), and harvested the chimeras at later embryonic stages
      (between 9-12 days of incubation). The donor and host tissues fused well with
      each other, with known major fiber pathways connecting the zebra finch and quail
      parts of the brain. However, the overall sizes of chimeric finch telencephala
      were larger than non-transplanted finch telencephala at the same developmental
      stages, even though the proportional sizes of telencephalic subregions and fiber
      tracts were similar to normal finches. There were no significant changes in the
      size of chimeric quail host midbrains, even though they were innervated by the
      physically smaller zebra finch brain, including the smaller retinae of the finch
      eyes. Chimeric zebra finch telencephala had a decreased cell density relative to
      normal finches. However, cell nucleus size differences between each species were
      maintained as in normal birds. These results suggest that telencephalic size
      development is partially cell-interdependent, and that the mechanisms controlling
      the size of different brain regions may be functionally independent.

PMID- 22860133
TI  - Roles of the kinase TAK1 in TRAF6-dependent signaling by CD40 and its oncogenic
      viral mimic, LMP1.
AB  - The Epstein-Barr virus (EBV)-encoded protein latent membrane protein 1 (LMP1) is
      essential for EBV-mediated B cell transformation and plays a critical role in the
      development of post-transplant B cell lymphomas. LMP1 also contributes to the
      exacerbation of autoimmune diseases such as systemic lupus erythematosus (SLE).
      LMP1 is a functional mimic of the tumor necrosis factor receptor (TNFR)
      superfamily member CD40, and relies on TNFR-associated factor (TRAF) adaptor
      proteins to mediate signaling. However, LMP1 activation signals to the B cell are
      amplified and sustained compared to CD40 signals. We previously demonstrated that
      LMP1 and CD40 use TRAF molecules differently. Although associating with CD40 and
      LMP1 via separate mechanisms, TRAF6 plays a significant role in signal
      transduction by both. It is unknown whether TRAF6 mediates CD40 versus LMP1
      functions via distinct or shared pathways. In this study, we tested the
      hypothesis that TRAF6 uses the kinase TAK1 to trigger important signaling
      pathways following both CD40 and LMP1 stimulation. We determined that TAK1 was
      required for JNK activation and interleukin-6 (IL-6) production mediated by CD40
      and LMP1, in both mouse and human B cells. Additionally, TRAF3 negatively
      regulated TRAF6-dependent, CD40-mediated TAK1 activation by limiting TRAF6
      recruitment. This mode of regulation was not observed for LMP1 and may contribute
      to the dysregulation of LMP1 compared to CD40 signals.

PMID- 22860134
TI  - Multi-neuronal refractory period adapts centrally generated behaviour to reward.
AB  - Oscillating neuronal circuits, known as central pattern generators (CPGs), are
      responsible for generating rhythmic behaviours such as walking, breathing and
      chewing. The CPG model alone however does not account for the ability of animals
      to adapt their future behaviour to changes in the sensory environment that signal
      reward. Here, using multi-electrode array (MEA) recording in an established
      experimental model of centrally generated rhythmic behaviour we show that the
      feeding CPG of Lymnaea stagnalis is itself associated with another, and hitherto
      unidentified, oscillating neuronal population. This extra-CPG oscillator is
      characterised by high population-wide activity alternating with population-wide
      quiescence. During the quiescent periods the CPG is refractory to activation by
      food-associated stimuli. Furthermore, the duration of the refractory period
      predicts the timing of the next activation of the CPG, which may be minutes into
      the future. Rewarding food stimuli and dopamine accelerate the frequency of the
      extra-CPG oscillator and reduce the duration of its quiescent periods. These
      findings indicate that dopamine adapts future feeding behaviour to the
      availability of food by significantly reducing the refractory period of the
      brain's feeding circuitry.

PMID- 22860135
TI  - Falling out of time: enhanced memory for scenes presented at behaviorally
      irrelevant points in time in posttraumatic stress disorder (PTSD).
AB  - Spontaneous encoding of the visual environment depends on the behavioral
      relevance of the task performed simultaneously. If participants identify target
      letters or auditory tones while viewing a series of briefly presented natural and
      urban scenes, they demonstrate effective scene recognition only when a target,
      but not a behaviorally irrelevant distractor, appears together with the scene.
      Here, we show that individuals with posttraumatic stress disorder (PTSD), who
      witnessed the red sludge disaster in Hungary, show the opposite pattern of
      performance: enhanced recognition of scenes presented together with distractors
      and deficient recognition of scenes presented with targets. The recognition of
      trauma-related and neutral scenes was not different in individuals with PTSD. We
      found a positive correlation between memory for scenes presented with auditory
      distractors and re-experiencing symptoms (memory intrusions and flashbacks).
      These results suggest that abnormal encoding of visual scenes at behaviorally
      irrelevant events might be associated with intrusive experiences by disrupting
      the flow of time.

PMID- 22860136
TI  - Dispersed oil disrupts microbial pathways in pelagic food webs.
AB  - Most of the studies of microbial processes in response to the Deepwater Horizon
      oil spill focused on the deep water plume, and not on the surface communities.
      The effects of the crude oil and the application of dispersants on the coastal
      microbial food web in the northern Gulf of Mexico have not been well
      characterized even though these regions support much of the fisheries production
      in the Gulf. A mesocosm experiment was carried out to determine how the microbial
      community off the coast of Alabama may have responded to the influx of surface
      oil and dispersants. While the addition of glucose or oil alone resulted in an
      increase in the biomass of ciliates, suggesting transfer of carbon to higher
      trophic levels was likely; a different effect was seen in the presence of
      dispersant. The addition of dispersant or dispersed oil resulted in an increase
      in the biomass of heterotrophic prokaryotes, but a significant inhibition of
      ciliates, suggesting a reduction in grazing and decrease in transfer of carbon to
      higher trophic levels. Similar patterns were observed in two separate experiments
      with different starting nutrient regimes and microbial communities suggesting
      that the addition of dispersant and dispersed oil to the northern Gulf of Mexico
      waters in 2010 may have reduced the flow of carbon to higher trophic levels,
      leading to a decrease in the production of zooplankton and fish on the Alabama
      shelf.

PMID- 22860137
TI  - Is human immunodeficiency virus infection a risk factor for Strongyloides
      stercoralis hyperinfection and dissemination.

PMID- 22860138
TI  - Nigeria: "Ground Zero" for the high prevalence neglected tropical diseases.

PMID- 22860139
TI  - Alkhurma viral hemorrhagic fever virus: proposed guidelines for detection,
      prevention, and control in Saudi Arabia.

PMID- 22860140
TI  - Activation of indoleamine 2,3-dioxygenase in patients with scrub typhus and its
      role in growth restriction of Orientia tsutsugamushi.
AB  - BACKGROUND: Our earlier genome-wide expression study revealed up-regulation of a
      tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in patients
      with scrub typhus. This gene has been previously reported to have anti-microbial
      activity in a variety of infectious diseases; therefore, we aimed to prove
      whether it is also involved in host defense against Orientia tsutsugamushi (OT)
      infection. METHODOLOGY/PRINCIPAL FINDINGS: Using LC-MS, we observed an increased
      ratio of serum L-kynurenine to serum L-tryptophan in patients with scrub typhus,
      which suggests an active catalytic function of this enzyme upon the illness. To
      evaluate the effect of IDO1 activation on OT infection, a human macrophage-like
      cell line THP-1 was used as a study model. Although transcription of IDO1 was
      induced by OT infection, its functional activity was not significantly enhanced
      unless the cells were pretreated with IFN-gamma, a potent inducer of IDO1. When
      the degree of infection was evaluated by quantitative real-time PCR, the relative
      number of OT 47 kDa gene per host genes, or infection index, was markedly reduced
      by IFN-gamma treatment as compared to the untreated cultures at five days post
      infection. Inhibition of IDO1 activity in IFN-gamma treated cultures by 1-methyl
      L-tryptophan, a competitive inhibitor of IDO1, resulted in partial restoration of
      infection index; while excessive supplementation of L-tryptophan in IFN-gamma
      treated cultures raised the index to an even higher level than that of the
      untreated ones. Altogether, these data implied that IDO1 was partly involved in
      restriction of OT growth caused by IFN-gamma through deprivation of tryptophan.
      CONCLUSIONS/SIGNIFICANCE: Activation of IDO1 appeared to be a defensive mechanism
      downstream of IFN-gamma that limited intracellular expansion of OT via tryptophan
      depletion. Our work provided not only the first link of in vivo activation of
      IDO1 and IFN-gamma-mediated protection against OT infection but also highlighted
      the promise of this multifaceted gene in scrub typhus research.

PMID- 22860141
TI  - Dengue infection in children in Ratchaburi, Thailand: a cohort study. I.
      Epidemiology of symptomatic acute dengue infection in children, 2006-2009.
AB  - BACKGROUND: There is an urgent need to field test dengue vaccines to determine
      their role in the control of the disease. Our aims were to study dengue
      epidemiology and prepare the site for a dengue vaccine efficacy trial. METHODS
      AND FINDINGS: We performed a prospective cohort study of children in primary
      schools in central Thailand from 2006 through 2009. We assessed the epidemiology
      of dengue by active fever surveillance for acute febrile illness as detected by
      school absenteeism and telephone contact of parents, and dengue diagnostic
      testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified
      in 2882, 3104, 2717 and 2312 student person-years over the four years,
      respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008
      and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus
      (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype
      1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and
      DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42
      (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever
      (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease
      severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in
      DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection.
      CONCLUSION: The results illustrate the high incidence of dengue with all four
      DENV serotypes in primary school children, with approximately 50% of disease
      manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria
      for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this
      type are required for clinical trials to evaluate the efficacy of dengue vaccines
      in large scale clinical trials.

PMID- 22860143
TI  - Integration of deworming into HIV care and treatment: a neglected opportunity.

PMID- 22860142
TI  - Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51.
AB  - BACKGROUND: Chagas Disease, a WHO- and NIH-designated neglected tropical disease,
      is endemic in Latin America and an emerging infection in North America and Europe
      as a result of population moves. Although a major cause of morbidity and
      mortality due to heart failure, as well as inflicting a heavy economic burden in
      affected regions, Chagas Disease elicits scant notice from the pharmaceutical
      industry because of adverse economic incentives. The discovery and development of
      new routes to chemotherapy for Chagas Disease is a clear priority.
      METHODOLOGY/PRINCIPAL FINDINGS: The similarity between the membrane sterol
      requirements of pathogenic fungi and those of the parasitic protozoon Trypanosoma
      cruzi, the causative agent of Chagas human cardiopathy, has led to repurposing
      anti-fungal azole inhibitors of sterol 14alpha-demethylase (CYP51) for the
      treatment of Chagas Disease. To diversify the therapeutic pipeline of anti
      Chagasic drug candidates we exploited an approach that included directly probing
      the T. cruzi CYP51 active site with a library of synthetic small molecules.
      Target-based high-throughput screening reduced the library of ~104,000 small
      molecules to 185 hits with estimated nanomolar K(D) values, while cross
      validation against T. cruzi-infected skeletal myoblast cells yielded 57 active
      hits with EC(50) <10 uM. Two pools of hits partially overlapped. The top hit
      inhibited T. cruzi with EC(50) of 17 nM and was trypanocidal at 40 nM.
      CONCLUSIONS/SIGNIFICANCE: The hits are structurally diverse, demonstrating that
      CYP51 is a rather permissive enzyme target for small molecules. Cheminformatic
      analysis of the hits suggests that CYP51 pharmacology is similar to that of other
      cytochromes P450 therapeutic targets, including thromboxane synthase (CYP5),
      fatty acid omega-hydroxylases (CYP4), 17alpha-hydroxylase/17,20-lyase (CYP17) and
      aromatase (CYP19). Surprisingly, strong similarity is suggested to glutaminyl
      peptide cyclotransferase, which is unrelated to CYP51 by sequence or structure.
      Lead compounds developed by pharmaceutical companies against these targets could
      also be explored for efficacy against T. cruzi.

PMID- 22860144
TI  - Detection of antibiotic resistance in leprosy using GenoType LepraeDR, a novel
      ready-to-use molecular test.
AB  - BACKGROUND: Although leprosy is efficiently treated by multidrug therapy,
      resistance to first-line (dapsone, rifampin) and to second-line drugs
      (fluoroquinolones) was described worldwide. Since Mycobacterium leprae is not
      growing in vitro, phenotypic susceptibility testing requires a one year
      experiment in the mouse model and this is rarely performed. Genetics on
      antibiotic resistance provide the basis for molecular tests able to detect for
      antibiotic resistance in leprosy. METHODOLOGY/PRINCIPAL FINDINGS: A reverse
      hybridization DNA strip test was developed as the GenoType LepraeDR test. It
      includes DNA probes for the wild-type sequence of regions of rpoB, gyrA and folP
      genes and probes for the prevalent mutations involved in acquired resistance to
      rifampin, fluoroquinolones and dapsone, respectively. The performances of the
      GenoType LepraeDR test were evaluated by comparing its results on 120 M. leprae
      strains, previously studied for resistance by the reference drug in vivo
      susceptibility method in the mouse footpad and for mutations in the gene regions
      described above by PCR-sequencing. The results of the test were 100% concordant
      with those of PCR sequencing and the mouse footpad test for the resistant
      strains: 16 strains resistant to rifampin, 22 to dapsone and 4 to ofloxacin with
      mutations (numbering system of the M. leprae genome) in rpoB (10 S456L, 1 S456F,
      1 S456M + L458V, 1 H451Y, 1 G432S + H451D, 1 T433I + D441Y and 1 Q438V), in folP1
      (8 P55L, 3 P55R, 7 T53I, 3 T53A, 1 T53V) and gyrA (4 A91V), respectively.
      Concordance was 98.3% for the susceptible strains, two strains showing a mutation
      at the codon 447 that in fact was not conferring resistance as shown by the in
      vivo method. CONCLUSIONS/SIGNIFICANCE: The GenoType LepraeDR test is a
      commercially available test that accurately detects for antibiotic resistance in
      leprosy cases. The test is easy to perform and could be implemented in endemic
      countries.

PMID- 22860145
TI  - Identification and characterization of argonaute protein, Ago2 and its associated
      small RNAs in Schistosoma japonicum.
AB  - BACKGROUND: The complex life cycle of the genus Schistosoma drives the parasites
      to employ subtle developmentally dependent gene regulatory machineries. Small non
      coding RNAs (sncRNAs) are essential gene regulatory factors that, through their
      impact on mRNA and genome stability, control stage-specific gene expression.
      Abundant sncRNAs have been identified in this genus. However, their functionally
      associated partners, Argonaute family proteins, which are the key components of
      the RNA-induced silencing complex (RISC), have not yet been fully explored.
      METHODOLOGY/PRINCIPAL FINDINGS: Two monoclonal antibodies (mAbs) specific to
      Schistosoma japonicum Argonaute protein Ago2 (SjAgo2), but not SjAgo1 and SjAgo3,
      were generated. Soluble adult worm antigen preparation (SWAP) was subjected to
      immunoprecipitation with the mAbs and the captured SjAgo2 protein was
      subsequently confirmed by Western blot and mass spectrometry (MS) analysis. The
      small RNA population associated with native SjAgo2 in adult parasites was
      extracted from the immunoprecipitated complex and subjected to library
      construction. High-through-put sequencing of these libraries yielded a total of
      ~50 million high-quality reads. Classification of these small RNAs showed that
      endogenous siRNAs (endo-siRNAs) generated from transposable elements (TEs),
      especially from the subclasses of LINE and LTR, were prominent. Further
      bioinformatics analysis revealed that siRNAs derived from ten types of well
      defined retrotransposons were dramatically enriched in the SjAgo2-specific
      libraries compared to small RNA libraries constructed with total small RNAs from
      separated adult worms. These results suggest that a key function of SjAgo2 is to
      maintain genome stability through suppressing the activities of retrotransposons.
      CONCLUSIONS/SIGNIFICANCE: In this study, we identified and characterized one of
      the three S. japonicum Argonautes, SjAgo2, and its associated small RNAs were
      found to be predominantly derived from particular classes of retrotransposons.
      Thus, a major function of SjAgo2 appears to associate with the maintenance of
      genome stability via suppression of retroelements. The data advance our
      understanding of the gene regulatory mechanisms in the blood fluke.

PMID- 22860146
TI  - A diagnostics platform for the integrated mapping, monitoring, and surveillance
      of neglected tropical diseases: rationale and target product profiles.

PMID- 22860147
TI  - Spontaneous clearance of a secondary Buruli ulcer lesion emerging ten months
      after completion of chemotherapy--a case report from Togo.

PMID- 22860148
TI  - Evaluation of circulating cathodic antigen (CCA) urine-tests for diagnosis of
      Schistosoma mansoni infection in Cameroon.
AB  - BACKGROUND: The Kato-Katz is the most common diagnostic method for Schistosoma
      mansoni infection. However, the day-to-day variability in host egg-excretion and
      its low detection sensitivity are major limits for its use in low transmission
      zones and after widespread chemotherapy. We evaluated the accuracy of circulating
      cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In
      comparison, a low sensitive CCA test (CCA-L) was assessed. METHODOLOGY: THE STUDY
      WAS CONDUCTED IN THREE SETTINGS: two foci with single S. mansoni infections
      (settings A and B), and one mixed S. mansoni - S. haematobium focus (setting C).
      Stool and urine samples were collected from school-children on three consecutive
      days. Triplicate Kato-Katz readings were performed per stool sample. Each urine
      sample was tested with one CCA and only the first urine sample was subjected to
      CCA-L. Urine samples were also examined for S. haematobium eggs using the
      filtration method and for microhaematuria using urine reagent strips. Overall,
      625 children provided three stool and three urine samples. PRINCIPAL FINDINGS:
      Considering nine Kato-Katz thick smears as 'reference' diagnostic test, the
      prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C,
      respectively. The prevalence of S. haematobium in setting C was 12.0%. The
      sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine
      samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B,
      and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%,
      64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection
      with S. haematobium did not influence the CCA test results for S. mansoni
      diagnosis. CONCLUSIONS/SIGNIFICANCE: Urine CCA revealed higher sensitivity than
      CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato
      Katz. It seems an attractive method for S. mansoni diagnosis.

PMID- 22860149
TI  - Research on motor neuron diseases konzo and neurolathyrism: trends from 1990 to
      2010.
AB  - Konzo (caused by consumption of improperly processed cassava, Manihot esculenta)
      and neurolathyrism (caused by prolonged overconsumption of grass pea, Lathyrus
      sativus) are two distinct non-infectious upper motor neurone diseases with
      identical clinical symptoms of spastic paraparesis of the legs. They affect many
      thousands of people among the poor in the remote rural areas in the central and
      southern parts of Africa afflicting them with konzo in Ethiopia and in the Indian
      sub-continent with neurolathyrism. Both diseases are toxico-nutritional problems
      due to monotonous consumption of starchy cassava roots or protein-rich grass pea
      seeds as a staple, especially during drought and famine periods. Both foods
      contain toxic metabolites (cyanogenic glycosides in cassava and the neuro
      excitatory amino acid beta-ODAP in grass pea) that are blamed for theses
      diseases. The etiology is also linked to the deficiency in the essential sulfur
      amino acids that protect against oxidative stress. The two diseases are not
      considered reportable by the World Health Organization (WHO) and only estimated
      numbers can be found. This paper analyzes research performance and determines
      scientific interest in konzo and neurolathyrism. A literature search of over 21
      years (from 1990 to 2010) shows that in terms of scientific publications there is
      little interest in these neglected motorneurone diseases konzo and neurolathyrism
      that paralyze the legs. Comparison is made with HTLV-1/TSP, an infectious disease
      occurring mainly in Latin America of which the clinical manifestation is similar
      to konzo and neurolathyrism and requires a differential diagnosis. Our findings
      emphasize the multidisciplinary nature of studies on these neglected diseases,
      which however have not really captured the attention of decision makers and
      project planners, especially when compared with the infectious HTLV-1/TSP. Konzo
      and neurolathyrism can be prevented by a balanced diet.

PMID- 22860151
TI  - Whole organism high-content screening by label-free, image-based Bayesian
      classification for parasitic diseases.
AB  - Sole reliance on one drug, Praziquantel, for treatment and control of
      schistosomiasis raises concerns about development of widespread resistance,
      prompting renewed interest in the discovery of new anthelmintics. To discover new
      leads we designed an automated label-free, high content-based, high throughput
      screen (HTS) to assess drug-induced effects on in vitro cultured larvae
      (schistosomula) using bright-field imaging. Automatic image analysis and Bayesian
      prediction models define morphological damage, hit/non-hit prediction and larval
      phenotype characterization. Motility was also assessed from time-lapse images. In
      screening a 10,041 compound library the HTS correctly detected 99.8% of the hits
      scored visually. A proportion of these larval hits were also active in an adult
      worm ex-vivo screen and are the subject of ongoing studies. The method allows,
      for the first time, screening of large compound collections against schistosomes
      and the methods are adaptable to other whole organism and cell-based screening by
      morphology and motility phenotyping.

PMID- 22860150
TI  - Regulatory T cells enhance susceptibility to experimental Trypanosoma congolense
      infection independent of mouse genetic background.
AB  - BACKGROUND: BALB/c mice are highly susceptible while C57BL/6 are relatively
      resistant to experimental Trypanosoma congolense infection. Although regulatory T
      cells (Tregs) have been shown to regulate the pathogenesis of experimental T.
      congolense infection, their exact role remains controversial. We wished to
      determine whether Tregs contribute to distinct phenotypic outcomes in BALB/c and
      C57BL/6 mice and if so how they operate with respect to control of parasitemia
      and production of disease-exacerbating proinflammatory cytokines.
      METHODOLOGY/FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally
      (i.p) with 10(3)T. congolense clone TC13 and both the kinetics of Tregs expansion
      and intracellular cytokine profiles in the spleens and livers were monitored
      directly ex vivo by flow cytometry. In some experiments, mice were injected with
      anti-CD25 mAb prior or post T. congolense infection or adoptively (by intravenous
      route) given highly enriched naive CD25(+) T lymphocytes prior to T. congolense
      infection and the inflammatory cytokine/chemokine levels and survival were
      monitored. In contrast to a transient and non significant increase in the
      percentages and absolute numbers of CD4(+)CD25(+)Foxp3(+) T cells (Tregs) in
      C57BL/6 mouse spleens and livers, a significant increase in the percentage and
      absolute numbers of Tregs was observed in spleens of infected BALB/c mice.
      Ablation or increasing the number of CD25(+) cells in the relatively resistant
      C57BL/6 mice by anti-CD25 mAb treatment or by adoptive transfer of CD25(+) T
      cells, respectively, ameliorates or exacerbates parasitemia and production of
      proinflammatory cytokines. CONCLUSION: Collectively, our results show that
      regulatory T cells contribute to susceptibility in experimental murine
      trypanosomiasis in both the highly susceptible BALB/c and relatively resistant
      C57BL/6 mice.

PMID- 22860152
TI  - Seroprevalence of Chagas infection in the donor population.
AB  - We retrospectively calculated the prevalence and epidemiologic characteristics of
      Chagas infection in the New York blood donor population over three years
      utilizing the New York Blood Center's database of the New York metropolitan area
      donor population. Seventy Trypanosoma cruzi positive donors were identified from
      among 876,614 donors over a 3-year period, giving an adjusted prevalence of
      0.0083%, with 0.0080% in 2007, 0.0073% in 2008, and 0.0097% in 2009. When
      filtered only for self-described "Hispanic/Latino" donors, there were 52 Chagas
      positive donors in that 3-year period (among 105,122 self-described Hispanic
      donors) with an adjusted prevalence of 0.052%, with 0.055% in 2007, 0.047% in
      2008, and 0.053% in 2009. In conclusion, we found a persistent population of
      patients with Chagas infection in the New York metropolitan area donor
      population. There was geographic localization of cases which aligned with Latin
      American immigration clusters.

PMID- 22860154
TI  - A simple strain typing assay for Trypanosoma cruzi: discrimination of major
      evolutionary lineages from a single amplification product.
AB  - BACKGROUND: Trypanosoma cruzi is the causative agent of Chagas' Disease. The
      parasite has a complex population structure, with six major evolutionary
      lineages, some of which have apparently resulted from ancestral hybridization
      events. Because there are important biological differences between these
      lineages, strain typing methods are essential to study the T. cruzi species.
      Currently, there are a number of typing methods available for T. cruzi, each with
      its own advantages and disadvantages. However, most of these methods are based on
      the amplification of a variable number of loci. METHODOLOGY/PRINCIPAL FINDINGS:
      We present a simple typing assay for T. cruzi, based on the amplification of a
      single polymorphic locus: the TcSC5D gene. When analyzing sequences from this
      gene (a putative lathosterol/episterol oxidase) we observed a number of
      interesting polymorphic sites, including 1 tetra-allelic, and a number of
      informative tri- and bi-allelic SNPs. Furthermore, some of these SNPs were
      located within the recognition sequences of two commercially available
      restriction enzymes. A double digestion with these enzymes generates a unique
      restriction pattern that allows a simple classification of strains in six major
      groups, corresponding to DTUs TcI-TcIV, the recently proposed Tcbat lineage, and
      TcV/TcVI (as a group). Direct sequencing of the amplicon allows the
      classification of strains into seven groups, including the six currently
      recognized evolutionary lineages, by analyzing only a few discriminant
      polymorphic sites. CONCLUSIONS/SIGNIFICANCE: Based on these findings we propose a
      simple typing assay for T. cruzi that requires a single PCR amplification
      followed either by restriction fragment length polymorphism analysis, or direct
      sequencing. In the panel of strains tested, the sequencing-based method displays
      equivalent inter-lineage resolution to recent multi- locus sequence typing
      assays. Due to their simplicity and low cost, the proposed assays represent a
      good alternative to rapidly screen strain collections, providing the cornerstone
      for the development of robust typing strategies.

PMID- 22860153
TI  - Significantly reduced intensity of infection but persistent prevalence of
      schistosomiasis in a highly endemic region in Mali after repeated treatment.
AB  - BACKGROUND: Preventive chemotherapy against schistosomiasis has been implemented
      since 2005 in Mali, targeting school-age children and adults at high risk. A
      cross-sectional survey was conducted in 2010 to evaluate the impact of repeated
      treatment among school-age children in the highly-endemic region of Segou.
      METHODOLOGY/PRINCIPAL FINDINGS: The survey was conducted in six sentinel schools
      in three highly-endemic districts, and 640 school children aged 7-14 years were
      examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed
      with the urine filtration and the Kato-Katz method respectively. Overall
      prevalence of S. haematobium infection was 61.7%, a significant reduction of 30%
      from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni
      infection was 12.7% which was not significantly different from the baseline.
      Overall mean intensity of S. haematobium and S. mansoni infection was 180.4
      eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2
      eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of
      81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was
      reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and
      heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both
      significantly (p<0.01). Mathematical modelling suggests that the observed results
      were in line with the expected changes. CONCLUSIONS/SIGNIFICANCE: Significant
      reduction in intensity of infection on both infections and modest but significant
      reduction in S. haematobium prevalence were achieved in highly-endemic Segou
      region after repeated chemotherapy. However, persistent prevalence of both
      infections and relatively high level of intensity of S. mansoni infection suggest
      that more intensified control measures be implemented in order to achieve the
      goal of schistosomiasis elimination. In addition, closer monitoring and
      evaluation activities are needed in the programme to monitor the drug tolerance
      and to adjust treatment focus.

PMID- 22860155
TI  - ACS chemical neuroscience molecule spotlight on viibryd (Vilazodone).
AB  - On January 21, 2011, the U.S. Food and Drug Administration approved Viibryd, a
      new selective serotonin reuptake inhibitor (SSRI), to treat major depressive
      disorder in adults developed by Clinical Data, Inc.

PMID- 22860156
TI  - Adenosine A(2A) Receptor Antagonists and Parkinson's Disease.
AB  - This Review summarizes and updates the work on adenosine A(2A) receptor
      antagonists for Parkinson's disease from 2006 to the present. There have been
      numerous publications, patent applications, and press releases within this time
      frame that highlight new medicinal chemistry approaches to this attractive and
      promising target to treat Parkinson's disease. The Review is broken down by
      scaffold type and will discuss the efforts to optimize particular scaffolds for
      activity, pharmacokinetics, and other drug discovery parameters. The majority of
      approaches focus on preparing selective A(2A) antagonists, but a few approaches
      to dual A(2A)/A(1) antagonists will also be highlighted. The in vivo profiles of
      compounds will be highlighted and discussed to compare activities across
      different chemical series. A clinical report and update will be given on
      compounds that have entered clinical trials.

PMID- 22860157
TI  - Biocytin-derived MRI contrast agent for longitudinal brain connectivity studies.
AB  - To investigate the connectivity of brain networks noninvasively and dynamically,
      we have developed a new strategy to functionalize neuronal tracers and designed a
      biocompatible probe that can be visualized in vivo using magnetic resonance
      imaging (MRI). Furthermore, the multimodal design used allows combined ex vivo
      studies with microscopic spatial resolution by conventional histochemical
      techniques. We present data on the functionalization of biocytin, a well-known
      neuronal tract tracer, and demonstrate the validity of the approach by showing
      brain networks of cortical connectivity in live rats under MRI, together with the
      corresponding microscopic details, such as fibers and neuronal morphology under
      light microscopy. We further demonstrate that the developed molecule is the first
      MRI-visible probe to preferentially trace retrograde connections. Our study
      offers a new platform for the development of multimodal molecular imaging tools
      of broad interest in neuroscience, that capture in vivo the dynamics of large
      scale neural networks together with their microscopic characteristics, thereby
      spanning several organizational levels.

PMID- 22860158
TI  - Defining the phosphodiesterase superfamily members in rat brain microvessels.
AB  - Eleven phosphodiesterase (PDE) families are known, each having several different
      isoforms and splice variants. Recent evidence indicates that expression of
      individual PDE family members is tissue-specific. Little is known concerning
      detailed PDE component expression in brain microvessels where the blood-brain
      barrier and the local cerebral blood flow are thought to be regulated by PDEs.
      The present study attempted to identify PDE family members that are expressed in
      brain microvessels. Adult male F344 rats were sacrificed and blocks of the
      cerebral cortex and infratentorial areas were dissected. Microvessels were
      isolated using a filtration method, and total RNA was extracted. RNA quality and
      quantity were determined using an Agilent bioanalyzer. The isolated cortical and
      infratentorial microvessel total RNA amounts were 2720 +/- 750 ng (n = 2) and 250
      +/- 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated
      that there were 16 PDE transcripts in the PDE superfamily, exhibiting
      quantifiable density in the microvessels. An additional immunofluorescent study
      verified that PDE4D (cAMP-specific) and PDE5A (cGMP-specific) were colocalized
      with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats
      and Sprague-Dawley rats (n = 3-6/strain). In addition, PDE4D and PDE5A were found
      to be colocalized with alpha-smooth muscle actin which delineates cerebral
      arteries and arterioles as well as pericytes. In conclusion, a filtration method
      followed by microarray analyses allows PDE components to be identified in brain
      microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed
      in rat brain microvessels.

PMID- 22860159
TI  - A safe, blood-brain barrier permeable triphenylmethane dye inhibits amyloid-beta
      neurotoxicity by generating nontoxic aggregates.
AB  - Growing evidence suggests that on-pathway amyloid-beta (Abeta) oligomers are
      primary neurotoxic species and have a direct correlation with the onset of
      Alzheimer's disease (AD). One promising therapeutic strategy to block AD
      progression is to reduce the levels of these neurotoxic Abeta species using small
      molecules. While several compounds have been shown to modulate Abeta aggregation,
      compounds with such activity combined with safety and high blood-brain barrier
      (BBB) permeability have yet to be reported. Brilliant Blue G (BBG) is a close
      structural analogue of a U.S. Food and Drug Administration (FDA)-approved food
      dye and has recently garnered prominent attention as a potential drug to treat
      spinal cord injury due to its neuroprotective effects along with BBB permeability
      and high degree of safety. In this work, we demonstrate that BBG is an effective
      Abeta aggregation modulator, which reduces Abeta-associated cytotoxicity in a
      dose-dependent manner by promoting the formation of off-pathway, nontoxic
      aggregates. Comparative studies of BBG and three structural analogues, Brilliant
      Blue R (BBR), Brilliant Blue FCF (BBF), and Fast Green FCF (FGF), revealed that
      BBG is most effective, BBR is moderately effective, and BBF and FGF are least
      effective in modulating Abeta aggregation and cytotoxicity. Therefore, the two
      additional methyl groups of BBG and other structural differences between the
      congeners are important in the interaction of BBG with Abeta leading to formation
      of nontoxic Abeta aggregates. Our findings support the hypothesis that generating
      nontoxic aggregates using small molecule modulators is an effective strategy for
      reducing Abeta cytotoxicity. Furthermore, key structural features of BBG
      identified through structure-function studies can open new avenues into
      therapeutic design for combating AD.

PMID- 22860161
TI  - ACS chemical neuroscience molecule spotlight on RG1678.
AB  - RG1678 is a glycine transporter-1 inhibitor currently in Phase III trials for the
      treatment of the negative symptoms of schizophrenia and is being developed by
      Roche (in combination with Chugai). Recent Phase II data shows that RG1678 is
      effective in reducing the negative symptoms when given in combination with second
      generation antipsychotics.

PMID- 22860160
TI  - Phosphorylation of alpha-Synuclein at Y125 and S129 alters its metal binding
      properties: implications for understanding the role of alpha-Synuclein in the
      pathogenesis of Parkinson's Disease and related disorders.
AB  - alpha-Synuclein (alpha-syn) is a 140-amino acid protein that plays a central role
      in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies.
      However, the molecular determinants that are responsible for triggering and/or
      propagating alpha-syn aggregation and toxicity remain poorly understood. Several
      studies have suggested that there are direct interactions between different
      metals and alpha-syn, but the role of metal ions and alpha-syn in the
      pathogenesis of PD is not firmly established. Interestingly, the majority of
      disease-associated post-translational modifications (PTMs) (e.g., truncation,
      phosphorylation, and nitration) of alpha-syn occur at residues within the C
      terminal region (Y125, S129, Y133, and Y136) and in very close proximity to the
      putative metal binding sites. Therefore, we hypothesized that phosphorylation
      within this domain could influence the alpha-syn-metal interactions. In this
      paper, we sought to map the interactions between the di- and trivalent cations,
      Cu(II), Pb(II), Fe(II), and Fe(III), and the C-terminal region of alpha-syn
      encompassing residues 107-140 and to determine how phosphorylation at S129 or
      Y125 alters the specificity and binding affinity of metals using electrospray
      ionization-mass spectrometry (ESI-MS) and fluorescence spectroscopy. We
      demonstrate that D115-M116 and P128-S129 act as additional Cu(II) binding sites
      and show for the first time that the residues P128-S129 and D119 are also
      involved in Pb(II) and Fe(II) coordination, although D119 is not essential for
      binding to Fe(II) and Pb(II). Furthermore, we demonstrate that phosphorylation at
      either Y125 or S129 increases the binding affinity of Cu(II), Pb(II), and Fe(II),
      but not Fe(III). Additionally, we also show that phosphorylations at these
      residues lead to a shift in the binding sites of metal ions from the N-terminus
      to the C-teminus. Together, our findings provide critical insight into and expand
      our understanding of the molecular and structural bases underlying the
      interactions between alpha-syn and metal ions, including the identification of
      novel metal binding sites, and highlight the potential importance of cross-talk
      between post-translational modifications and metal ion binding in modulating
      alpha-syn functional and aggregation properties that are regulated by its C
      terminal domain.

PMID- 22860162
TI  - Detection of multiple sclerosis from exhaled breath using bilayers of polycyclic
      aromatic hydrocarbons and single-wall carbon nanotubes.
AB  - A cross-reactive array of polycyclic aromatic hydrocarbons and single wall carbon
      nanotube bilayers was designed for the detection of volatile organic compounds
      (tentatively, hexanal and 5-methyl-undecane) that identify the presence of
      disease in the exhaled breath of patients with multiple sclerosis. The sensors
      showed excellent discrimination between hexanal, 5-methyl-undecane, and other
      confounding volatile organic compounds. Results obtained from a clinical study
      consisting of 51 volunteers showed that the sensors could discriminate between
      multiple sclerosis and healthy states from exhaled breath samples with 85.3%
      sensitivity, 70.6% specificity, and 80.4% accuracy. These results open new
      frontiers in the development of a fast, noninvasive, and inexpensive medical
      diagnostic tool for the detection and identification of multiple sclerosis. The
      results could serve also as a launching pad for the discrimination between
      different subphases or stages of multiple sclerosis as well as for the
      identification of multiple sclerosis patients who would respond well to
      immunotherapy.

PMID- 22860163
TI  - "Clicked" sugar-curcumin conjugate: modulator of amyloid-beta and tau peptide
      aggregation at ultralow concentrations.
AB  - The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative
      of curcumin with amplified bioefficacy in modulating amyloid-beta and tau peptide
      aggregation is presented. Curcumin inhibits amyloid-beta and tau peptide
      aggregation at micromolar concentrations; the sugar-curcumin conjugate inhibits
      Abeta and tau peptide aggregation at concentrations as low as 8 nM and 0.1 nM,
      respectively. In comparison to curcumin, this conveniently synthesized
      Alzheimer's drug candidate is a more powerful antioxidant.

PMID- 22860164
TI  - Label-free visualization of ultrastructural features of artificial synapses via
      cryo-EM.
AB  - The ultrastructural details of presynapses formed between artificial substrates
      of submicrometer silica beads and hippocampal neurons are visualized via cryo
      electron microscopy (cryo-EM). The silica beads are derivatized by poly-d-lysine
      or lipid bilayers. Molecular features known to exist at presynapses are clearly
      present at these artificial synapses, as visualized by cryo-EM. Key synaptic
      features such as the membrane contact area at synaptic junctions, the presynaptic
      bouton containing presynaptic vesicles, as well as microtubular structures can be
      identified. This is the first report of the direct, label-free observation of
      ultrastructural details of artificial synapses.

PMID- 22860165
TI  - Special issue on the pharmacology and medicinal chemistry of allosteric
      modulators of metabotropic glutamate receptors (mGluRs).

PMID- 22860166
TI  - ACS chemical neuroscience molecule spotlight on STX209 (arbaclofen).
AB  - STX209 (arbaclofen) is a gamma-amino butyric acid type B (GABA(B)) receptor
      agonist from Seaside Therapeutics currently in clinical trials for autism
      spectrum disorders (ASD). The company has initiated a phase 2b study after
      positive results from a phase 2a trial, announced September 2010
      (http://www.seasidetherapeutics.com/sites/default/files/STX209_ASD_P2b
      Trial_Initiation%206%2021%202011%20Final.pdf).

PMID- 22860167
TI  - Recent progress in the synthesis and characterization of group II metabotropic
      glutamate receptor allosteric modulators.
AB  - Group II metabotropic glutamate (mGlu) receptors consist of the metabotropic
      glutamate 2 (mGlu(2)) and metabotropic glutamate 3 (mGlu(3)) receptor subtypes
      which modulate glutamate transmission by second messenger activation to
      negatively regulate the activity of adenylyl cyclase. Excessive accumulation of
      glutamate in the perisynaptic extracellular region triggers mGlu(2) and mGlu(3)
      receptors to inhibit further release of glutamate. There is growing evidence that
      the modulation of glutamatergic neurotransmission by small molecule modulators of
      Group II mGlu receptors has significant potential for the treatment of several
      neuropsychiatric and neurodegenerative diseases. This review provides an overview
      of recent progress on the synthesis and pharmacological characterization of
      positive and negative allosteric modulators of the Group II mGlu receptors.

PMID- 22860168
TI  - Recent advances in the medicinal chemistry of the metabotropic glutamate receptor
      1 (mGlu1).
AB  - This Review summarizes the medicinal chemistry found in publications on both
      orthosteric and allosteric modulators of the metabotropic glutamate receptor 1
      (mGlu(1)) from 2005 to the present. The time period covered by the scope of this
      current review has been particularly rich in mGlu(1)-related publications with
      numbers quadrupling when compared to the preceding five year period of 2000-2005.
      Publications in the field peaked in 2007 with over 35 articles appearing in the
      peer reviewed literature in the course of that year. Given that glutamate is one
      of the primary excitatory neurotransmitters in the mammalian central nervous
      system (CNS), it is unsurprising that it acts upon several receptors that are
      considered to be of potential therapeutic interest for many indications.
      Orthosteric and allosteric modulation of the receptor is possible, with a logical
      extrapolation to the chemotypes used for each strategy. The last five years of
      publications have yielded many mGlu(1) selective antagonist chemotypyes, most of
      which have shown efficacy in pain in vivo models. However, the primary impact of
      these compounds has been to highlight the mechanistic safety risks of mGlu(1)
      antagonism, independent of chemotype. As a review in medicinal chemistry, the
      primary focus of this paper will be on the design and, to a lesser degree,
      synthetic strategies for the delivery of subtype selective, CNS penetrant,
      druglike compounds through a "medchem" program, targeting modulators of the
      mGlu(1) receptor.

PMID- 22860169
TI  - Fragile X syndrome: an update on developing treatment modalities.
AB  - Intellectual disability (ID; mental retardation) is considered an immutable
      condition. Current medical practices are aimed at relieving symptoms and not at
      altering the underlying cognitive deficits. Scientific advancements from the past
      decade have led to the exciting possibility that ID may now be treatable.
      Moreover, pharmaceutical therapies targeting the most common form of inherited
      ID, Fragile X syndrome (FXS), may become the new benchmark for central nervous
      system (CNS) drug discovery: seeking cures for neurodevelopmental disorders.

PMID- 22860170
TI  - Recent progress on the identification of metabotropic glutamate 4 receptor
      ligands and their potential utility as CNS therapeutics.
AB  - This Review describes recent activity in the advancement of ligands for the
      metabotropic glutamate 4 receptor subtype and their potential utility as central
      nervous system (CNS) therapeutics. Until recently, there was a paucity of
      compounds with suitable selectivity and druglike properties to elucidate the
      value of this target. The search for selective entities has led several groups to
      the investigation of allosteric modulators as a path to optimization of potential
      ligands. Recent efforts, discussed here, have afforded a variety of derivatives
      with improvements in potency, solubility, and pharmacokinetic properties that
      garner support for continued investigation and optimization.

PMID- 22860171
TI  - Progress toward positive allosteric modulators of the metabotropic glutamate
      receptor subtype 5 (mGluR5).
AB  - This Review describes recent trends in the development of small molecule mGlu(5)
      positive allosteric modulators (PAMs). A large body of pharmacological, genetic,
      electrophysiological, and in vivo behavioral evidence has accumulated over the
      past decade which continues to support the hypothesis and rationale for the
      activation of the metabotropic glutamate receptor subtype 5 (mGlu(5)) as a viable
      and promising target for the development of novel antipsychotics. Until recently,
      functionally efficacious and potent mGlu(5) PAMs have been somewhat structurally
      limited in scope and slow to emerge. This Review will discuss efforts since late
      2008 which have provided novel mGlu(5) PAM chemotypes, offering ligands with a
      diverse range of pharmacological, physicochemical, and DMPK properties that were
      previously unavailable. In addition, significant biological studies of importance
      in the past few years using the well established PAMs known as DFB, CPPHA, CDPPB,
      and ADX-47273 will be discussed.

PMID- 22860172
TI  - ACS chemical neuroscience molecule spotlight on contrave.
AB  - Contrave is an investigational fixed-dose combination drug of naltrexone and
      bupropion currently in Phase III clinical trials for the treatment of obesity.
      Orexigen Therapeutics, Inc. has demonstrated efficacy of their product and is
      currently addressing FDA safety concerns and deciding future actions.

PMID- 22860173
TI  - Biofunctionalized magnetic nanoparticles for specifically detecting biomarkers of
      Alzheimer's disease in vitro.
AB  - Magnetic nanoparticles biofunctionalized with antibodies against beta-amyloid-40
      (Abeta-40) and Abeta-42, which are promising biomarkers related to Alzheimer's
      disease (AD), were synthesized. We characterized the size distribution, saturated
      magnetizations, and stability of the magnetic nanoparticles conjugated with anti
      Abeta antibody. In combination with immunomagnetic reduction technology, it is
      demonstrated such biofunctionalized magnetic nanoparticles are able to label
      Abetas specifically. The ultralow-detection limits of assaying Abetas in vitro
      using the magnetic nanoparticles via immunomagnetic reduction are determined to a
      concentration of ~10 ppt (10 pg/mL). Further, immunomagnetic reduction signals of
      Abeta-40 and Abeta-42 in human plasma from normal samples and AD patients were
      analyzed, and the results showed a significant difference between these two
      groups. These results show the feasibility of using magnetic nanoparticles with
      Abetas as reagents for assaying low-concentration Abetas through immunomagnetic
      reduction, and also provide a promising new method for early diagnosis of
      Alzheimer's disease from human blood plasma.

PMID- 22860175
TI  - Tuning photochromic ion channel blockers.
AB  - Photochromic channel blockers provide a conceptually simple and convenient way to
      modulate neuronal activity with light. We have recently described a family of
      azobenzenes that function as tonic blockers of K(v) channels but require UV-A
      light to unblock and need to be actively switched by toggling between two
      different wavelengths. We now introduce red-shifted compounds that fully operate
      in the visible region of the spectrum and quickly turn themselves off in the
      dark. Furthermore, we have developed a version that does not block effectively in
      the dark-adapted state, can be switched to a blocking state with blue light, and
      reverts to the inactive state automatically. Photochromic blockers of this type
      could be useful for the photopharmacological control of neuronal activity under
      mild conditions.

PMID- 22860174
TI  - 3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a
      novel adenosine receptor antagonist with A(2A)-mediated neuroprotective effects.
AB  - In this study, compound FTBI (3-(2-furyl)-10-(2-phenylethyl)[1,2,4]triazino[4,3
      a]benzimidazol-4(10H)-one) was selected from a small library of
      triazinobenzimidazole derivatives as a potent A(2A) adenosine receptor (AR)
      antagonist and tested for its neuroprotective effects against two different kinds
      of dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and
      methamphetamine (METH), in rat PC12 and in human neuroblastoma SH-SY5Y cell
      lines. FTBI, in a concentration range corresponding to its affinity for A(2A) AR
      subtype, significantly increased the number of viable PC12 cells after their
      exposure to METH and, to a similar extent, to MPP+, as demonstrated in both
      trypan blue exclusion assay and in cytological staining. These neuroprotective
      effects were also observed with a classical A(2A) AR antagonist, ZM241385, and
      appeared to be completely counteracted by the AR agonist, NECA, supporting A(2A)
      ARs are directly involved in FTBI-mediated effects. Similarly, in human SH-SY5Y
      cells, FTBI was able to prevent cell toxicity induced by MPP+ and METH, showing
      that this A(2A) AR antagonist has a neuroprotective effect independently by the
      specific cell model. Altogether these results demonstrate that the A(2A) AR
      blockade mediates cell protection against neurotoxicity induced by dopaminergic
      neurotoxins in dopamine containing cells, supporting the potential use of A(2A)
      AR antagonists in dopaminergic degenerative diseases including Parkinson's
      disease.

PMID- 22860177
TI  - ACS chemical neuroscience molecule spotlight on Begacestat (GSI-953).
AB  - A "second generation" gamma-secretase, Begacestat (GSI-953), which is more
      selective against Notch-signaling, has shown promise in recent Phase I clinical
      trials. Begacestat, a novel, 2,5-disubsitituted thiophene sulfonamide from Wyeth
      (now Pfizer) is under evaluation for the treatment of Alzheimer's disease.

PMID- 22860178
TI  - Ceftriaxone ameliorates motor deficits and protects dopaminergic neurons in 6
      hydroxydopamine-lesioned rats.
AB  - Parkinson's disease is caused by the degeneration of dopaminergic neurons in
      substantia nigra. There is no current promising treatment for neuroprotection of
      dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been
      reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.
      R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky,
      S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher,
      P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing
      glutamate transporter expression Nature433, 73-77). In the present study,
      efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and
      amelioration of motor deficits in a rat model of Parkinson's disease were
      investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats.
      Using behavioral tests, grip strength and numbers of apomorphine-induced
      contralateral rotation were declined in the ceftriaxone-treated group. More
      importantly, cell death of dopaminergic neurons was found to decrease. In
      addition, both the protein expression and immunoreactivity for GLT-1 were up
      regulated. The present results strongly indicate that ceftriaxone is a potential
      agent in the treatment of Parkinson's disease.

PMID- 22860179
TI  - Dopamine and serotonin modulate human GABArho1 receptors expressed in Xenopus
      laevis oocytes.
AB  - GABArho1 receptors are highly expressed in bipolar neurons of the retina and to a
      lesser extent in several areas of the central nervous system (CNS), and dopamine
      and serotonin are also involved in the modulation of retinal neural transmission.
      Whether these biogenic amines have a direct effect on ionotropic GABA receptors
      was not known. Here, we report that GABArho1 receptors, expressed in X. laevis
      oocytes, were negatively modulated by dopamine and serotonin and less so by
      octopamine and tyramine. Interestingly, these molecules did not have effects on
      GABA(A) receptors. 5-Carboxamido-tryptamine and apomorphine did not exert evident
      effects on any of the receptors. Schild plot analyses of the inhibitory actions
      of dopamine and serotonin on currents elicited by GABA showed slopes of 2.7 +/-
      0.3 and 6.1 +/- 1.8, respectively, indicating a noncompetitive mechanism of
      inhibition. The inhibition of GABArho1 currents was independent of the membrane
      potential and was insensitive to picrotoxin, a GABA receptor channel blocker and
      to the GABArho-specific antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl
      phosphinic acid (TPMPA). Dopamine and serotonin changed the sensitivity of
      GABArho1 receptors to the inhibitory actions of Zn(2+). In contrast, La(3+)
      potentiated the amplitude of the GABA currents generated during negative
      modulation by dopamine (EC(50) 146 MUM) and serotonin (EC(50) 196 MUM). The
      functional role of the direct modulation of GABArho receptors by dopamine and
      serotonin remains to be elucidated; however, it may represent an important
      modulatory pathway in the retina, where GABArho receptors are highly expressed
      and where these biogenic amines are abundant.

PMID- 22860180
TI  - Discovery of a Tamoxifen-related compound that suppresses glial l-glutamate
      transport activity without interaction with estrogen receptors.
AB  - We recently found that tamoxifen suppresses l-glutamate transport activity of
      cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter
      inhibitory activity from the estrogen receptor-mediated genomic effects, we
      synthesized several compounds structurally related to tamoxifen. Among them, we
      identified two compounds, 1 (YAK01) and 3 (YAK037), which potently inhibited l
      glutamate transporter activity. The inhibitory effect of 1 was found to be
      mediated through estrogen receptors and the mitogen-activated protein kinase
      (MAPK)/phosphatidylinositol 3-kinase (PI3K) pathway, though 1 showed greatly
      reduced transactivation activity compared with that of 17beta-estradiol. On the
      other hand, compound 3 exerted its inhibitory effect through an estrogen receptor
      independent and MAPK-independent, but PI3K-dependent pathway, and showed no
      transactivation activity. Compound 3 may represent a new platform for developing
      novel l-glutamate transporter inhibitors with higher brain transfer rates and
      reduced adverse effects.

PMID- 22860181
TI  - Effects of translocator protein (18 kDa) ligands on microglial activation and
      neuronal death in the quinolinic-acid-injected rat striatum.
AB  - There is evidence that excitotoxicity and prolonged microglial activation are
      involved in neuronal death in neurodegenerative disorders. Activated microglia
      express various molecules, including the translocator protein 18 kDa (TSPO;
      formerly known as the peripheral benzodiazepine receptor) on the outer
      mitochondrial membrane. The TSPO is a novel target for neuroprotective treatments
      which aim to reduce microglial activation. The effect of PK 11195 and three other
      TSPO ligands on the level of microglial activation and neuronal survival was
      evaluated in a quinolinic acid (QUIN) rat model of excitotoxic neurodegeneration.
      All three ligands were neuroprotective at a level comparable to PK 11195. All of
      the ligands decreased microglial activation following the injection of QUIN but
      had no effect on astrogliosis. Interestingly, we also observed neuroprotective
      effects from the vehicle, dimethyl sulfoxide (DMSO).

PMID- 22860183
TI  - ACS chemical neuroscience molecule spotlight on BMS-708163.
AB  - BMS-708163 is a novel, sulfonamide containing gamma-secretase inhibitor from
      Bristol-Myers Squibb Co. currently in Phase II clinical trials for the treatment
      of Alzheimer's disease (AD).

PMID- 22860182
TI  - Characterization of non-nitrocatechol pan and isoform specific catechol-O
      methyltransferase inhibitors and substrates.
AB  - Reduced dopamine neurotransmission in the prefrontal cortex has been implicated
      as causal for the negative symptoms and cognitive deficit associated with
      schizophrenia; thus, a compound which selectively enhances dopamine
      neurotransmission in the prefrontal cortex may have therapeutic potential.
      Inhibition of catechol-O-methyltransferase (COMT, EC 2.1.1.6) offers a unique
      advantage, since this enzyme is the primary mechanism for the elimination of
      dopamine in cortical areas. Since membrane bound COMT (MB-COMT) is the
      predominant isoform in human brain, a high throughput screen (HTS) to identify
      novel MB-COMT specific inhibitors was completed. Subsequent optimization led to
      the identification of novel, non-nitrocatechol COMT inhibitors, some of which
      interact specifically with MB-COMT. Compounds were characterized for in vitro
      efficacy versus human and rat MB and soluble (S)-COMT. Select compounds were
      administered to male Wistar rats, and ex vivo COMT activity, compound levels in
      plasma and cerebrospinal fluid (CSF), and CSF dopamine metabolite levels were
      determined as measures of preclinical efficacy. Finally, novel non-nitrocatechol
      COMT inhibitors displayed less potent uncoupling of the mitochondrial membrane
      potential (MMP) compared to tolcapone as well as nonhepatotoxic entacapone, thus
      mitigating the risk of hepatotoxicity.

PMID- 22860184
TI  - Small molecule kinase inhibitors for LRRK2 and their application to Parkinson's
      disease models.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder.
      Several single gene mutations have been linked to this disease. Mutations in the
      gene encoding leucine-rich repeat kinase 2 (LRRK2) indicate LRRK2 as promising
      therapeutic target for the treatment of PD. LRRK2 mutations were observed in
      sporadic as well as familial PD patients and have been investigated intensively.
      LRRK2 is a large and complex protein, with multiple enzymatic and protein
      interaction domains, each of which is effected by mutations. The most common
      mutation in PD patients is G2019S. Several LRRK2 inhibitors have been reported
      already, although the crystal structure of LRRK2 has not yet been determined.
      This review provides a summary of known LRRK2 inhibitors and will discuss recent
      in vitro and in vivo results of these inhibitors.

PMID- 22860185
TI  - Detection of asymptomatic nigrostriatal dopaminergic lesion in rats by exhaled
      air analysis using carbon nanotube sensors.
AB  - The ante-mortem diagnosis of Parkinson's disease (PD) still relies on clinical
      symptoms. Biomarkers could in principle be used for the early detection of PD
      related neuronal damage, but no validated, inexpensive, and simple biomarkers are
      available yet. Here we report on the breath-print of presymptomatic PD in rats,
      using a model with 50% lesion of dopaminergic neurons in substantia nigra.
      Exhaled breath was collected from 19 rats (10 lesioned and 9 sham operated) and
      analyzed using organically functionalized carbon nanotube sensors. Discriminant
      factor analysis detected statistically significant differences between the study
      groups and a classification accuracy of 90% was achieved using leave-one-out
      cross-validation. The sensors' breath-print was supported by determining
      statistically significant differences of several volatile organic compounds in
      the breath of the lesioned rats and the sham operated rats, using gas
      chromatography combined with mass spectrometry. The observed breath-print shows
      potential for cost-effective, fast, and reliable early PD detection.

PMID- 22860186
TI  - Abeta(1-42) assembly in the presence of scyllo-inositol derivatives:
      identification of an oxime linkage as important for the development of assembly
      inhibitors.
AB  - To identify a lead skeleton structure for optimization of scyllo-inositol-based
      inhibitors of amyloid-beta peptide (Abeta) aggregation, we have synthesized
      aldoxime, hydroxamate, carbamate, and amide linked scyllo-inositol derivatives.
      These structures represent backbones that can be readily expanded into a wide
      array of derivatives. They also provide conservative modifications of the scyllo
      inositol backbone, as they maintain the display of the equatorial polar atoms,
      preserving the stereochemical requirement necessary for maximum inhibition of
      Abeta(1-42) fiber formation. In addition, a reliable work plan for screening
      derivatives was developed in order to preferentially identify a backbone(s)
      structure that prevents fibrillogenesis and stabilizes nontoxic small molecular
      weight oligomers, as we have previously reported for scyllo-inositol. In the
      present studies, we have adapted a high throughput ELISA-based oligomerization
      assay followed by atomic force microscopy to validate the results screen
      compounds. The lead compounds were then tested for toxicity and ability to rescue
      Abeta(1-42) induced toxicity in vitro and the affinity of the compounds for
      Abeta(1-42) compared by mass spectrometry. The data to suggest that compounds
      must maintain a planar conformation to exhibit activity similar to scyllo
      inositol and that the oxime derivative represents the lead backbone for future
      development.

PMID- 22860187
TI  - X-ray absorption spectroscopy at the sulfur K-edge: a new tool to investigate the
      biochemical mechanisms of neurodegeneration.
AB  - Sulfur containing molecules such as thiols, disulfides, sulfoxides, sulfonic
      acids, and sulfates may contribute to neurodegenerative processes. However,
      previous study in this field has been limited by the lack of in situ analytical
      techniques. This limitation may now be largely overcome following the development
      of synchrotron radiation X-ray absorption spectroscopy at the sulfur K-edge,
      which has been validated as a novel tool to investigate and image the speciation
      of sulfur in situ. In this investigation, we build the foundation required for
      future application of this technique to study and image the speciation of sulfur
      in situ within brain tissue. This study has determined the effect of sample
      preparation and fixation methods on the speciation of sulfur in thin sections of
      rat brain tissue, determined the speciation of sulfur within specific brain
      regions (brain stem and cerebellum), and identified sulfur specific markers of
      peroxidative stress following metal catalyzed reactive oxygen species production.
      X-ray absorption spectroscopy at the sulfur K-edge is now poised for an exciting
      new range of applications to study thiol redox, methionine oxidation, and the
      role of taurine and sulfatides during neurodegeneration.

PMID- 22860188
TI  - A simple method for quantifying functional selectivity and agonist bias.
AB  - Activation of seven-transmembrane (7TM) receptors by agonists does not always
      lead to uniform activation of all signaling pathways mediated by a given
      receptor. Relative to other ligands, many agonists are "biased" toward producing
      subsets of receptor behaviors. A hallmark of such "functional selectivity" is
      cell type dependence; this poses a particular problem for the profiling of
      agonists in whole cell test systems removed from the therapeutic one(s). Such
      response-specific cell-based variability makes it difficult to guide medicinal
      chemistry efforts aimed at identifying and optimizing therapeutically meaningful
      agonist bias. For this reason, we present a scale, based on the Black and Leff
      operational model, that contains the key elements required to describe 7TM
      agonism, namely, affinity (K(A) (-1)) for the receptor and efficacy (tau) in
      activating a particular signaling pathway. Utilizing a "transduction coefficient"
      term, log(tau/K(A)), this scale can statistically evaluate selective agonist
      effects in a manner that can theoretically inform structure-activity studies
      and/or drug candidate selection matrices. The bias of four chemokines for CCR5
      mediated inositol phosphate production versus internalization is quantified to
      illustrate the practical application of this method. The independence of this
      method with respect to receptor density and the calculation of statistical
      estimates of confidence of differences are specifically discussed.

PMID- 22860189
TI  - Potential of a gamma-glutamyl-transpeptidase-stable glutathione analogue against
      amyloid-beta toxicity.
AB  - The antioxidant properties of glutathione (GSH) and their relevance to oxidative
      stress induced pathological states such as Alzheimer's disease is well
      established. The utility of GSH itself as a pharmacotherapeutic agent for such
      disorders is limited because of the former's lability to breakdown through amide
      cleavage by the ubiquitous enzyme gamma-glutamyl transpeptidase (gamma-GT). In
      the present study, a GSH analogue, Psi-GSH, where the gamma-glutamylcysteine
      amide linkage is replaced with a ureide linkage, was synthesized. Psi-GSH was
      found to be stable toward gamma-GT mediated breakdown. Psi-GSH fulfilled four
      cardinal properties of GSH, namely, traversing across the blood brain barrier
      (BBB) via the GSH active uptake machinery, replacing GSH in the glyoxalase-I
      mediated detoxification of methylglyoxal, protecting cells against chemical
      oxidative insult, and finally lowering the cytotoxicity of amyloid-beta peptide.
      These results validate Psi-GSH as a viable metabolically stable replacement for
      GSH and establish it as a potential preclinical candidate for treatment of
      oxidative stress mediated pathology.

PMID- 22860190
TI  - An azobenzene photoswitch sheds light on turn nucleation in amyloid-beta self
      assembly.
AB  - Amyloid-beta (Abeta) self-assembly into cross-beta amyloid fibrils is implicated
      in a causative role in Alzheimer's disease pathology. Uncertainties persist
      regarding the mechanisms of amyloid self-assembly and the role of metastable
      prefibrillar aggregates. Abeta fibrils feature a sheet-turn-sheet motif in the
      constituent beta-strands; as such, turn nucleation has been proposed as a rate
      limiting step in the self-assembly pathway. Herein, we report the use of an
      azobenzene beta-hairpin mimetic to study the role turn nucleation plays on Abeta
      self-assembly. [3-(3-Aminomethyl)phenylazo]phenylacetic acid (AMPP) was
      incorporated into the putative turn region of Abeta42 to elicit temporal control
      over Abeta42 turn nucleation; it was hypothesized that self-assembly would be
      favored in the cis-AMPP conformation if beta-hairpin formation occurs during
      Abeta self-assembly and that the trans-AMPP conformer would display attenuated
      fibrillization propensity. It was unexpectedly observed that the trans-AMPP
      Abeta42 conformer forms fibrillar constructs that are similar in almost all
      characteristics, including cytotoxicity, to wild-type Abeta42. Conversely, the
      cis-AMPP Abeta42 congeners formed nonfibrillar, amorphous aggregates that
      exhibited no cytotoxicity. Additionally, cis-trans photoisomerization resulted in
      rapid formation of native-like amyloid fibrils and trans-cis conversion in the
      fibril state reduced the population of native-like fibrils. Thus, temporal
      photocontrol over Abeta turn conformation provides significant insight into Abeta
      self-assembly. Specifically, Abeta mutants that adopt stable beta-turns form
      aggregate structures that are unable to enter folding pathways leading to cross
      beta fibrils and cytotoxic prefibrillar intermediates.

PMID- 22860191
TI  - Role of histamine and its receptors in cerebral ischemia.
AB  - Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and
      it plays a major role in the pathogenic progression after cerebral ischemia.
      Extracellular histamine increases gradually after ischemia, and this may come
      from histaminergic neurons or mast cells. Histamine alleviates neuronal damage
      and infarct volume, and it promotes recovery of neurological function after
      ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest
      that histamine alleviates excitotoxicity, suppresses the release of glutamate and
      dopamine, and inhibits inflammation and glial scar formation. Histamine may also
      affect cerebral blood flow by targeting to vascular smooth muscle cells, and
      promote neurogenesis. Moreover, endogenous histamine is an essential mediator in
      the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons,
      glia, vascular cells, and inflammatory cells, histamine is likely to be an
      important target in cerebral ischemia. But due to its low penetration of the
      blood-brain barrier and its wide actions in the periphery, histamine-related
      agents, like H3 antagonists and carnosine, show potential for cerebral ischemia
      therapy. However, important questions about the molecular aspects and
      pathophysiology of histamine and related agents in cerebral ischemia remain to be
      answered to form a solid scientific basis for therapeutic application.

PMID- 22860192
TI  - Modulation of thermoreceptor TRPM8 by cooling compounds.
AB  - ThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation
      channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both
      activated by cooling. TRPM8 is activated by innocuous cooling (<30  degrees C)
      and contributes to sensing unpleasant cold stimuli or mediating the effects of
      cold analgesia and is a receptor for menthol and icilin (mint-derived and
      synthetic cooling compounds, respectively). TRPA1 (Ankyrin family) is activated
      by noxious cold (<17  degrees C), icilin, and a variety of pungent compounds.
      Extensive amount of medicinal chemistry efforts have been published mainly in the
      form of patent literature on various classes of cooling compounds by various
      pharmaceutical companies; however, no prior comprehensive review has been
      published. When expressed in heterologous expression systems, such as Xenopus
      oocytes or mammalian cell lines, TRPM8 mediated currents are activated by a
      number of cooling compounds in addition to menthol and icilin. These include
      synthetic p-menthane carboxamides along with other class of compounds such as
      aliphatic/alicyclic alcohols/esters/amides, sulphones/sulphoxides/sulphonamides,
      heterocyclics, keto-enamines/lactams, and phosphine oxides. In the present
      review, the medicinal chemistry of various cooling compounds as activators of
      thermoTRPM8 channel will be discussed according to their chemical classes. The
      potential of these compounds to emerge as therapeutic agents is also discussed.

PMID- 22860193
TI  - Synthesis and in vitro evaluation of a biotinylated dextran-derived probe for
      molecular imaging.
AB  - Herein we report the design, synthesis, and in vitro evaluation of a gadolinium
      containing biotinylated dextran-derived molecular imaging probe as a prospective
      neuroanatomical tracer by means of magnetic resonance imaging (MRI). The probe
      was effectively taken up by cultured differentiated murine neuroblastoma cells
      and significantly enhanced the contrast in T(1)- and T(2)-weighted MR images of
      labeled cells under physiological conditions. A significant longitudinal
      relaxation rate enhancement in the presence of avidin was observed allowing the
      verification of the results in the end of noninvasive longitudinal MRI
      connectivity studies by post-mortem histology. The in vitro results indicate that
      the probe has the potential to be used in vivo to identify the organization of
      global neuronal networks in the brain with MRI.

PMID- 22860194
TI  - Transformation of Pro-Leu-Gly-NH2 peptidomimetic positive allosteric modulators
      of the dopamine D2 receptor into negative modulators.
AB  - The synthesis of dimethyl derivatives of 5.6.5 spiro bicyclic lactam Pro-Leu-Gly
      NH(2) peptidomimetics was carried out to test the hypothesis that by placing
      methyl groups on the beta-methylene carbon of the thiazolidine ring steric bulk
      would be introduced into the topological space that the beta-methylene carbon is
      believed to occupy in the negative allosteric modulators of the dopamine D(2)
      receptor. With such a modification, a positive allosteric modulator would be
      converted into a negative allosteric modulator. This hypothesis was shown to be
      correct as 3a and 4a where found to be negative allosteric modulators, whereas
      their unmethylated derivatives were positive allosteric modulators of the
      dopamine D(2) receptor.

PMID- 22860195
TI  - Structurally diverse GABA antagonists interact differently with open and closed
      conformational states of the rho1 receptor.
AB  - Ligands acting on receptors are considered to induce a conformational change
      within the ligand-binding site by interacting with specific amino acids. In this
      study, tyrosine 102 (Y102) located in the GABA binding site of the rho(1) subunit
      of the GABA(C) receptor was mutated to alanine (rho(1Y102A)), serine
      (rho(1Y102S)), and cysteine (rho(1Y102C)) to assess the role of this amino acid
      in the action of 12 known and 2 novel antagonists. Of the mutated receptors,
      rho(1Y102S) was constitutively active, providing an opportunity to assess the
      activity of antagonists on rho(1) receptors with a proportion of receptors
      existing in the open conformational state compared to those existing
      predominantly in the closed conformational state. It was found that the majority
      of antagonists studied were able to inhibit the constitutive activity displayed
      by rho(1Y102S), thus displaying inverse agonist activity. The exception was (+/-)
      4-aminocyclopent-1-enecarboxamide ((+/-)-4-ACPAM) (8) not exhibiting any inverse
      agonist activity, but acting explicitly on the closed conformational state of
      rho(1) receptors (rho(1) wild-type, rho(1Y102C) and rho(1Y102A)). It was also
      found that the GABA antagonists were more potent at the closed compared to the
      open conformational states of rho(1) receptors, suggesting that they may act by
      stabilizing closed conformational state and thus reducing activation by agonists.
      Furthermore, of the antagonists tested, Y102 was found to have the greatest
      influence on the antagonist activity of gabazine (SR-95531 (13)) and its analogue
      (SR-95813 (14)). This study contributes to our understanding of the mechanism of
      inverse agonism. This is important, as such agents are emerging as potential
      therapeutics.

PMID- 22860196
TI  - Isolated amyloid-beta(1-42) protofibrils, but not isolated fibrils, are robust
      stimulators of microglia.
AB  - Senile plaques composed of amyloid-beta protein (Abeta) are an unshakable feature
      of the Alzheimer's disease (AD) brain. Although there is significant debate on
      the role of the plaques in AD progression, there is little disagreement on their
      role in stimulating a robust inflammatory response within the context of the
      disease. Significant inflammatory markers such as activated microglia and
      cytokines are observed almost exclusively surrounding the plaques. However,
      recent evidence suggests that the plaque exterior may contain a measurable level
      of soluble Abeta aggregates. The observations that microglia activation in vivo
      is selectively stimulated by distinct Abeta deposits led us to examine what
      specific form of Abeta is the most effective proinflammatory mediator in vitro.
      We report here that soluble prefibrillar species of Abeta(1-42) were better than
      fibrils at inducing microglial tumor necrosis factor alpha (TNFalpha) production
      in either BV-2 and primary murine microglia. Reconstitution of Abeta(1-42) in
      NaOH followed by dilution into F-12 media and isolation with size exclusion
      chromatography (SEC) revealed classic curvilinear beta-sheet protofibrils 100 nm
      in length. The protofibrils, but not monomers, markedly activated BV-2 microglia.
      Comparisons were also made between freshly isolated protofibrils and Abeta(1-42)
      fibrils prepared from SEC-purified monomer. Surprisingly, while isolated fibrils
      had a much higher level of thioflavin T fluorescence per mole, they were not
      effective at stimulating either primary or BV-2 murine microglia compared to
      protofibrils. Furthermore, SEC-isolated Abeta(1-40) protofibrils exhibited
      significantly less activity than concentration-matched Abeta(1-42). This report
      is the first to demonstrate microglial activation by SEC-purified protofibrils,
      and the overall findings indicate that small, soluble Abeta(1-42) protofibrils
      induce much greater microglial activation than mature insoluble fibrils.

PMID- 22860197
TI  - Neuropeptide Y protects rat cortical neurons against beta-amyloid toxicity and re
      establishes synthesis and release of nerve growth factor.
AB  - Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed within
      central nervous system neurons. More recently, it has been shown that NPY is
      involved in Alzheimer's disease (AD), a disorder characterized by accumulation of
      amyloid beta-peptide (Abeta) in neurons. In a previous study, we investigated the
      effect of NPY on neuronal damage by exposing SH-SY5Y cells (an established human
      derived neuroblastoma cell line) to Abeta's pathogenic fragment 25-35 (Abeta(25
      35)). We found a NPY-neuroprotective action associated with changes in
      intracellular production of nerve growth factor (NGF), a member of the
      neurotrophin family. Since our results were encouraging, we decided to replicate
      our data using primary cortical neurons cultured in presence of Abeta(25-35), and
      investigated whether NPY had similar neuroprotective action. Moreover, since
      cortical neurons are able to produce and release NGF, we investigated whether the
      synthesis and release of NGF were modified in such experimental conditions. Our
      results showed that a preincubation with NPY counteracted the toxic effect of
      Abeta, as measured by increased cell viability. Moreover, NPY pretreatment had an
      effect on NGF since its intracellular synthesis was increased, release was
      normalized, and mRNA expression was downregulated. Notably, these effects on NGF
      were in the opposite direction of those produced by incubating the cells with
      Abeta alone. This study in primary cortical neurons supports the hypothesis that
      NPY may be a neuroprotective agent against beta-amyloid neurotoxicity. These data
      also suggest that NPY may influence the synthesis and the release of NGF by
      cortical neurons.

PMID- 22860198
TI  - BODIPY-based molecular probe for imaging of cerebral beta-amyloid plaques.
AB  - We designed and synthesized a BODIPY-based probe (BAP-1) for the imaging of beta
      amyloid plaques in the brain. In binding experiments in vitro, BAP-1 showed
      excellent affinity for synthetic Abeta aggregates. beta-Amyloid plaques in Tg2576
      mouse brain were clearly visualized with BAP-1. In addition, the labeling of beta
      amyloid plaques was demonstrated in vivo in Tg2576 mice. These results suggest
      BAP-1 to be a useful fluorescent probe for the optical imaging of cerebral beta
      amyloid plaques in patients with Alzheimer's disease.

PMID- 22860199
TI  - Solution structures of the prototypical 18 kDa translocator protein ligand, PK
      11195, elucidated with 1H/13C NMR spectroscopy and quantum chemistry.
AB  - Eighteen kilodalton translocator protein (TSPO) is an important target for drug
      discovery and for clinical molecular imaging of brain and peripheral inflammatory
      processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3
      isoquinoline carboxamide] is the major prototypical high-affinity ligand for
      TSPO. Elucidation of the solution structure of 1a is of interest for
      understanding small-molecule ligand interactions with the lipophilic binding site
      of TSPO. Dynamic (1)H/(13)C NMR spectroscopy of 1a revealed four quite stable but
      interconverting rotamers, due to amide bond and 2-chlorophenyl group rotation.
      These rotamers have been neglected in previous descriptions of the structure of
      1a and of the binding of 1a to TSPO. Here, we used quantum chemistry at the level
      of B3LYP/6-311+G(2d,p) to calculate (13)C and (1)H chemical shifts for the
      rotamers of 1a and for the very weak TSPO ligand, N-desmethyl-PK 11195 (1b).
      These data, plus experimental NMR data, were then used to characterize the
      structures of rotamers of 1a and 1b in organic solution. Energy barriers for both
      the amide bond and 2'-chlorophenyl group rotation of 1a were determined from
      dynamic (1)H NMR to be similar (ca.17 to 18 kcal/mol), and they compared well
      with those calculated at the level of B3LYP/6-31G*. Furthermore, the computed
      barrier for Z to E rotation is considerably lower in 1a(18.7 kcal/mol) than in 1b
      (25.4 kcal/mol). NMR (NOE) unequivocally demonstrated that the E rotamer of 1a is
      the more stable in solution by about 0.4 kcal/mol. These detailed structural
      findings will aid future TSPO ligand design and support the notion that TSPO
      prefers to bind ligands as amide E-rotamers.

PMID- 22860202
TI  - Endocannabinoid signaling in female reproduction.
AB  - Marijuana is a preparation of the flower, as well as the leaves and seeds, of the
      plant Cannabis sativa. Marijuana has been used for medicinal and recreational
      purposes for thousands of years due to its psychoactive effects including
      euphoria, sedation, and analgesia. Although it has been suspected for decades
      that marijuana has adverse effects on female fertility, the underlying molecular
      mechanism was not clear. The discovery of cannabinoid receptors and
      endocannabinoids has advanced studies if cannabinoid signaling. Since then,
      numerous studies have been published on cannabinoid signaling in female
      reproductive events, including preimplantation embryo development, oviductal
      embryo transport, embryo implantation, placentation, and parturition. This review
      focuses on various aspects of endocannabinoid signaling in female fertility.

PMID- 22860203
TI  - "Redundancy" of endocannabinoid inactivation: new challenges and opportunities
      for pain control.
AB  - Redundancy of metabolic pathways and molecular targets is a typical feature of
      all lipid mediators, and endocannabinoids, which were originally defined as
      endogenous agonists at cannabinoid CB(1) and CB(2) receptors, are no exception.
      In particular, the two most studied endocannabinoids, anandamide and 2
      arachidonoylglycerol, are inactivated through alternative biochemical routes,
      including hydrolysis and oxidation, and more than one enzyme might be used even
      for the same type of inactivating reaction. These enzymes also recognize as
      substrates other concurrent lipid mediators, whereas, in turn, endocannabinoids
      might interact with noncannabinoid receptors with subcellular distribution and
      ultimate biological actions either similar to or completely different from those
      of cannabinoid receptors. Even splicing variants of endocannabinoid hydrolyzing
      enzymes, such as FAAH-1, might play distinct roles in endocannabinoid
      inactivation. Finally, the products of endocannabinoid catabolism may have their
      own targets, with biological roles different from those of cannabinoid receptors.
      These peculiarities of endocannabinoid signaling have complicated the use of
      inhibitors of its inactivation mechanisms as a safer and more efficacious
      alternative to the direct targeting of cannabinoid receptors for the treatment of
      several pathological conditions, including pain. However, new strategies,
      including the rediscovery of "dirty drugs", and the use of certain natural
      products (including non-THC cannabis constituents), are emerging that might allow
      us to make a virtue of necessity and exploit endocannabinoid redundancy to
      develop new analgesics.

PMID- 22860204
TI  - Anandamide externally added to lipid vesicles containing trapped fatty acid amide
      hydrolase (FAAH) is readily hydrolyzed in a sterol-modulated fashion.
AB  - We show that anandamide (AEA) externally added to model membrane vesicles
      containing trapped fatty acid amide hydrolyase (FAAH) can be readily hydrolyzed,
      demonstrating facile, rapid anandamide movement across the lipid bilayer. The
      rate of hydrolysis is significantly facilitated by cholesterol and coprostanol,
      but not by cholesterol sulfate. The effects of sterol upon hydrolysis by FAAH
      bound to the outer surface of the bilayer were much smaller, although they
      followed the same pattern. We propose the facilitation of hydrolysis is a
      combination of the effects of sterol on accessibility of membrane-inserted
      endocannabinoids to surface protein, and on the rate of endocannabinod transport
      across the membrane bilayer.

PMID- 22860205
TI  - Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC
      like Morris water maze deficits in mice.
AB  - Acute administration of Delta(9)-tetrahydrocannabinol (THC) or exposure to
      marijuana smoke impairs short-term spatial memory in water maze tasks through a
      CB(1) receptor mechanism of action. N-Arachidonoylethanolamine (anandamide; AEA)
      and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids that are
      predominantly metabolized by the respective enzymes fatty acid amide hydrolase
      (FAAH) and monoacylglycerol lipase (MAGL). Although the MAGL inhibitor JZL184
      enhances short-term synaptic plasticity, it has yet to be evaluated in the Morris
      water maze. Previous research demonstrated that simultaneous, complete blockade
      of FAAH and MAGL produces full blown THC-like effects. Thus, in the following
      studies we tested whether dual blockade of FAAH and MAGL would impair learning in
      a repeated acquisition Morris water maze task. Mice treated with the dual
      FAAH/MAGL inhibitor JZL195 (20 mg/kg) as well as JZL184-treated FAAH -/- mice
      displayed robust deficits in Morris water maze performance that were similar in
      magnitude to THC-treated mice. While 20 or 40 mg/kg impaired water maze
      performance in FAAH -/- mice, only the high dose of JZL184 disrupted performance
      in FAAH +/+ mice. The memory impairing effects of JZL184 were blocked by the
      CB(1) receptor antagonist rimonabant. Neither JZL184 nor JZL195 impaired
      performance in a cued version of the water maze task, arguing against the notion
      that sensorimotor or motivational deficits accounted for the impaired acquisition
      performance. JZL184 increased 2-AG levels in the hippocampus, prefrontal cortex,
      and cerebellum to a similar degree in FAAH -/- and +/+ mice. FAAH -/- mice,
      regardless of drug treatment, possessed elevated AEA levels in each brain region
      assessed. The results of this study reveal that concomitant increases in AEA and
      2-AG disrupt short-term spatial memory performance in a manner similar to that of
      THC.

PMID- 22860206
TI  - Endogenous molecules stimulating N-acylethanolamine-hydrolyzing acid amidase
      (NAAA).
AB  - Fatty acid amide hydrolase (FAAH) plays the central role in the degradation of
      bioactive N-acylethanolamines such as the endocannabinoid
      arachidonoylethanolamide (anandamide) in brain and peripheral tissues. A
      lysosomal enzyme referred to as N-acylethanolamine-hydrolyzing acid amidase
      (NAAA) catalyzes the same reaction with preference to palmitoylethanolamide, an
      endogenous analgesic and neuroprotective substance, and is therefore expected as
      a potential target of therapeutic drugs. In the in vitro assays thus far
      performed, the maximal activity of NAAA was achieved in the presence of both
      nonionic detergent (Triton X-100 or Nonidet P-40) and the SH reagent
      dithiothreitol. However, endogenous molecules that might substitute for these
      synthetic compounds remain poorly understood. Here, we examined stimulatory
      effects of endogenous phospholipids and thiol compounds on recombinant NAAA.
      Among different phospholipids tested, choline- or ethanolamine-containing
      phospholipids showed potent effects, and 1 mM phosphatidylcholine increased NAAA
      activity by 6.6-fold. Concerning endogenous thiol compounds, dihydrolipoic acid
      at 0.1-1 mM was the most active, causing 8.5-9.0-fold stimulation. These results
      suggest that endogenous phospholipids and dihydrolipoic acid may contribute in
      keeping NAAA active in lysosomes. Even in the presence of phosphatidylcholine and
      dihydrolipoic acid, however, the preferential hydrolysis of palmitoylethanolamide
      was unaltered. We also investigated a possible compensatory induction of NAAA
      mRNA in brain and other tissues of FAAH-deficient mice. However, NAAA expression
      levels in all the tissues examined were not significantly altered from those in
      wild-type mice.

PMID- 22860207
TI  - Impact of embedded endocannabinoids and their oxygenation by lipoxygenase on
      membrane properties.
AB  - N-Arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol are the best
      characterized endocannabinoids. Their biological activity is subjected to
      metabolic control whereby a dynamic equilibrium among biosynthetic, catabolic,
      and oxidative pathways drives their intracellular concentrations. In particular,
      lipoxygenases can generate hydroperoxy derivatives of endocannabinoids, endowed
      with distinct activities within cells. The in vivo interaction between
      lipoxygenases and endocannabinoids is likely to occur within cell membranes;
      thus, we sought to ascertain whether a prototypical enzyme like soybean (Glycine
      max) 15-lipoxygenase-1 is able to oxygenate endocannabinoids embedded in
      synthetic vesicles and how these substances could affect the binding ability of
      the enzyme to different lipid bilayers. We show that (i) embedded
      endocannabinoids increase membrane fluidity; (ii) 15-lipoxygenase-1
      preferentially binds to endocannabinoid-containing bilayers; and that (iii) 15
      lipoxygenase-1 oxidizes embedded endocannabinoids and thus reduces fluidity and
      local hydration of membrane lipids. Together, the present findings reveal further
      complexity in the regulation of endocannabinoid signaling within the central
      nervous system, disclosing novel control by oxidative pathways.

PMID- 22860208
TI  - Endocannabinoid enzyme engineering: soluble human thio-monoacylglycerol lipase
      (sol-S-hMGL).
AB  - In the mammalian central nervous system, monoacylglycerol lipase (MGL) is
      principally responsible for inactivating the endocannabinoid signaling lipid 2
      arachidonoylglycerol (2-AG) and modulates cannabinoid-1 receptor (CB1R)
      desensitization and signal intensity. MGL is also a drug target for diseases in
      which CB1R stimulation may be therapeutic. To inform the design of human MGL
      (hMGL) inhibitors, we have engineered a Leu(Leu(169);Leu(176))-to
      Ser(Ser(169);Ser(176)) double hMGL mutant (sol-hMGL) which exhibited enhanced
      solubility properties, and we further mutated this variant by substituting its
      catalytic-triad Ser(122) with Cys (sol-S-hMGL). The hMGL variants hydrolyzed both
      2-AG and a fluorogenic reporter substrate with comparable affinities. Our results
      suggest that the hMGL cysteine mutant maintains the same overall architecture as
      wild-type hMGL. The results also underscore the superior nucleophilic nature of
      the reactive catalytic Ser(122) residue as compared to that of Cys(122) in the
      sol-S-hMGL mutant and suggest that the nucleophilic character of the Cys(122)
      residue is not commensurately enhanced within the three dimensional architecture
      of hMGL. The interaction of the sol-hMGL variants with the irreversible
      inhibitors AM6580 and N-arachidonylmaleimide (NAM) and the reversible inhibitor
      AM10212 was profiled. LC/MS analysis of tryptic digests from sol-S-hMGL directly
      demonstrate covalent modification of this variant by NAM and AM6580, consistent
      with enzyme thiol alkylation and carbamoylation, respectively. These data provide
      insight into hMGL catalysis, the key role of the nucleophilic character of
      Ser(122), and the mechanisms underlying hMGL inhibition by different classes of
      small molecules.

PMID- 22860209
TI  - Sativex-like combination of phytocannabinoids is neuroprotective in malonate
      lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2
      receptors.
AB  - We have investigated whether a 1:1 combination of botanical extracts enriched in
      either Delta(9)-tetrahydrocannabinol (Delta(9)-THC) or cannabidiol (CBD), which
      are the main constituents of the cannabis-based medicine Sativex, is
      neuroprotective in Huntington's disease (HD), using an experimental model of this
      disease generated by unilateral lesions of the striatum with the mitochondrial
      complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms
      that primarily involve apoptosis and microglial activation. We monitored the
      extent of this damage and the possible preservation of the striatal parenchyma by
      treatment with a Sativex-like combination of phytocannabinoids using different
      histological and biochemical markers. Results were as follows: (i) malonate
      increased the volume of edema measured by in vivo NMR imaging and the Sativex
      like combination of phytocannabinoids partially reduced this increase; (ii)
      malonate reduced the number of Nissl-stained cells, while enhancing the number of
      degenerating cells stained with FluoroJade-B, and the Sativex-like combination of
      phytocannabinoids reversed both effects; (iii) malonate caused a strong glial
      activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled
      with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both
      responses; and (iv) malonate increased the expression of inducible nitric oxide
      synthase and the neurotrophin IGF-1, and both responses were attenuated after the
      treatment with the Sativex-like combination of phytocannabinoids. We also wanted
      to establish whether targets within the endocannabinoid system (i.e., CB(1) and
      CB(2) receptors) are involved in the beneficial effects induced in this model by
      the Sativex-like combination of phytocannabinoids. This we did using selective
      antagonists for both receptor types (i.e., SR141716 and AM630) combined with the
      Sativex-like phytocannabinoid combination. Our results indicated that the effects
      of this combination are blocked by these antagonists and hence that they do
      result from an activation of both CB(1) and CB(2) receptors. In summary, this
      study provides preclinical evidence in support of a beneficial effect of the
      cannabis-based medicine Sativex as a neuroprotective agent capable of delaying
      signs of disease progression in a proinflammatory model of HD, which adds to
      previous data obtained in models priming oxidative mechanisms of striatal injury.
      However, the interest here is that, in contrast with these previous data, we have
      now obtained evidence that both CB(1) and CB(2) receptors appear to be involved
      in the effects produced by a Sativex-like phytocannabinoid combination, thus
      stressing the broad-spectrum properties of Sativex that may combine activity at
      the CB(1) and/or CB(2) receptors with cannabinoid receptor-independent actions.

PMID- 22860210
TI  - Characterization of the effects of reuptake and hydrolysis inhibition on
      interstitial endocannabinoid levels in the brain: an in vivo microdialysis study.
AB  - The present experiments employed in vivo microdialysis to characterize the
      effects of commonly used endocannabinoid clearance inhibitors on basal and
      depolarization-induced alterations in interstitial endocannabinoid levels in the
      nucleus accumbens of rat brain. Compounds targeting the putative endocannabinoid
      transporter and hydrolytic enzymes (FAAH and MAGL) were compared. The transporter
      inhibitor AM404 modestly enhanced depolarization-induced increases in 2
      arachidonoyl glycerol (2-AG) levels but did not alter levels of N-arachidonoyl
      ethanolamide (anandamide, AEA). The transport inhibitor UCM707 did not alter
      dialysate levels of either endocannabinoid. The FAAH inhibitors URB597 and PF
      3845 robustly increased AEA levels during depolarization without altering 2-AG
      levels. The MAGL inhibitor URB602 significantly enhanced depolarization-induced
      increases in 2-AG, but did not alter AEA levels. In contrast, the MAGL inhibitor
      JZL184 did not alter 2-AG or AEA levels under any condition tested. Finally, the
      dual FAAH/MAGL inhibitor JZL195 significantly enhanced depolarization-induced
      increases in both AEA and 2-AG levels. In contrast to the present observations in
      rats, prior work in mice has demonstrated a robust JZL184-induced enhancement of
      depolarization-induced increases in dialysate 2-AG. Thus, to further investigate
      species differences, additional tests with JZL184, PF-3845, and JZL195 were
      performed in mice. Consistent with prior reports, JZL184 significantly enhanced
      depolarization-induced increases in 2-AG without altering AEA levels. PF-3845 and
      JZL195 produced profiles in mouse dialysates comparable to those observed in
      rats. These findings confirm that interstitial endocannabinoid levels in the
      brain can be selectively manipulated by endocannabinoid clearance inhibitors.
      While PF-3845 and JZL195 produce similar effects in both rats and mice,
      substantial species differences in JZL184 efficacy are evident, which is
      consistent with previous studies.

PMID- 22860212
TI  - Ischemia-induced increase in microvascular phosphodiesterase 4D expression in rat
      hippocampus associated with blood brain barrier permeability: effect of age.
AB  - Phosphodiesterase 4D (PDE4D) is one of 16 PDEs expressed in cerebral
      microvessels, and may be involved in regulating blood-brain barrier (BBB)
      permeability. To assess the possible role of PDE4D in stroke-related injury in
      young versus aged rats, we measured microvascular PDE4D expression, parenchymal
      albumin immunoreactivity, and changes in the inside bore of the brain
      microvasculature. Ischemia caused severe hippocampal CA1 damage, associated with
      significant increases in vascular PDE4D and parenchymal albumin
      immunoreactivities. This effect was greater in the younger animals, which also
      had a greater increase in PDE4D expression. Ischemia significantly decreased
      tissue density in the perimicrovascular space in both young and aged animals. In
      addition, internal bore circumference and cross-sectional area of the hippocampal
      microvessels increased dramatically following ischemia. Increased PDE4D
      expression following cerebral ischemia may play a role in changing BBB
      permeability, which could secondarily affect ischemic outcome.

PMID- 22860211
TI  - O-hydroxyacetamide carbamates as a highly potent and selective class of
      endocannabinoid hydrolase inhibitors.
AB  - The two major endocannabinoid transmitters, anandamide (AEA) and 2
      arachidonoylglycerol (2-AG), are degraded by distinct enzymes in the nervous
      system, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL),
      respectively. FAAH and MAGL inhibitors cause elevations in brain AEA and 2-AG
      levels, respectively, and reduce pain, anxiety, and depression in rodents without
      causing the full spectrum of psychotropic behavioral effects observed with direct
      cannabinoid receptor-1 (CB1) agonists. These findings have inspired the
      development of several classes of endocannabinoid hydrolase inhibitors, most of
      which have been optimized to show specificity for either FAAH or MAGL or, in
      certain cases, equipotent activity for both enzymes. Here, we investigate an
      unusual class of O-hydroxyacetamide carbamate inhibitors and find that individual
      compounds from this class can serve as selective FAAH or dual FAAH/MAGL
      inhibitors in vivo across a dose range (0.125-12.5 mg kg(-1)) suitable for
      behavioral studies. Competitive and click chemistry activity-based protein
      profiling confirmed that the O-hydroxyacetamide carbamate SA-57 is remarkably
      selective for FAAH and MAGL in vivo, targeting only one other enzyme in brain,
      the additional 2-AG hydrolase ABHD6. These data designate O-hydroxyacetamide
      carbamates as a versatile chemotype for creating endocannabinoid hydrolase
      inhibitors that display excellent in vivo activity and tunable selectivity for
      FAAH-anandamide versus MAGL (and ABHD6)-2-AG pathways.

PMID- 22860213
TI  - Mass spectral charting of neuropeptidomic expression in the stomatogastric
      ganglion at multiple developmental stages of the lobster Homarus americanus.
AB  - The stomatogastric nervous system (STNS) of the American lobster Homarus
      americanus serves as a useful model for studies of neuromodulatory substances
      such as peptides and their roles in the generation of rhythmic behaviors. As a
      central component of the STNS, the stomatogastric ganglion (STG) is rich in
      neuropeptides and contains well-defined networks of neurons, serving as an
      excellent model system to study the effect of neuropeptides on the maturation of
      neural circuits. Here, we utilize multiple mass spectrometry (MS)-based
      techniques to study the neuropeptide content and abundance in the STG tissue as
      related to the developmental stage of the animal. Capillary electrophoresis (CE)
      MS was employed to unambiguously identify low abundance neuropeptide complements,
      which were not fully addressed using previous methods. In total, 35 neuropeptides
      from 7 different families were detected in the tissue samples. Notably, 10
      neuropeptides have been reported for the first time in this study. In addition,
      we utilized a relative quantitation method to compare neuropeptidomic expression
      at different developmental stages and observed sequential appearance of several
      neuropeptides. Multiple isoforms within the same peptide family tend to show
      similar trends of changes in relative abundance during development. We also
      determined that the relative abundances of tachykinin peptides increase as the
      lobster grows, suggesting that the maturation of circuit output may be influenced
      by the change of neuromodulatory input into the STG. Collectively, this study
      expands our knowledge about neuropeptides in the crustacean STNS and provides
      useful information about neuropeptide expression in the maturation process.

PMID- 22860214
TI  - Comparison of three amyloid assembly inhibitors: the sugar scyllo-inositol, the
      polyphenol epigallocatechin gallate, and the molecular tweezer CLR01.
AB  - Many compounds have been tested as inhibitors or modulators of amyloid beta
      protein (Abeta) assembly in hope that they would lead to effective, disease
      modifying therapy for Alzheimer's disease (AD). These compounds typically were
      either designed to break apart beta-sheets or selected empirically. Two such
      compounds, the natural inositol derivative scyllo-inositol and the green-tea
      derived flavonoid epigallocatechin gallate (EGCG), currently are in clinical
      trials. Similar to most of the compounds tested thus far, the mechanism of action
      of scyllo-inositol and EGCG is not understood. Recently, we discovered a novel
      family of assembly modulators, Lys-specific molecular tweezers, which act by
      binding specifically to Lys residues and modulate the self-assembly of amyloid
      proteins, including Abeta, into formation of nontoxic oligomers by a process
      specific mechanism (Sinha, S., Lopes, D. H., Du, Z., Pang, E. S., Shanmugam, A.,
      Lomakin, A., Talbiersky, P., Tennstaedt, A., McDaniel, K., Bakshi, R., Kuo, P.
      Y., Ehrmann, M., Benedek, G. B., Loo, J. A., Klarner, F. G., Schrader, T., Wang,
      C., and Bitan, G. (2011) Lysine-specific molecular tweezers are broad-spectrum
      inhibitors of assembly and toxicity of amyloid proteins. J. Am. Chem. Soc.133,
      16958-16969). Here, we compared side-by-side the capability of scyllo-inositol,
      EGCG, and the molecular tweezer CLR01 to inhibit Abeta aggregation and toxicity.
      We found that EGCG and CLR01 had comparable activity whereas scyllo-inositol was
      a weaker inhibitor. Exploration of the binding of EGCG and CLR01 to Abeta using
      heteronuclear solution-state NMR showed that whereas CLR01 bound to the two Lys
      and single Arg residues in Abeta monomers, only weak, nonspecific binding was
      detected for EGCG, leaving the binding mode of the latter unresolved.

PMID- 22860215
TI  - Developmental expression of orphan G protein-coupled receptor 50 in the mouse
      brain.
AB  - Mental disorders have a complex etiology resulting from interactions between
      multiple genetic risk factors and stressful life events. Orphan G protein-coupled
      receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar
      disorder and major depression in women, and there is additional genetic and
      functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and
      adaptive thermogenesis and torpor. However, in the absence of a ligand, a
      specific function has not been identified. Adult GPR50 expression has previously
      been reported in brain regions controlling the HPA axis, but its developmental
      expression is unknown. In this study, we performed extensive expression analysis
      of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in
      the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13
      (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we
      identified novel regions of Gpr50 expression, including brain stem nuclei
      involved in neurotransmitter signaling: the locus coeruleus, substantia nigra,
      and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50
      colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the
      hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the
      adult. With this study, we identify a link between GPR50 and neurotransmitter
      signaling and strengthen a likely role in stress response and energy homeostasis.

PMID- 22860216
TI  - A key role for lysine residues in amyloid beta-protein folding, assembly, and
      toxicity.
AB  - A combination of hydrophobic and electrostatic interactions is important in
      initiating the aberrant self-assembly process that leads to formation of toxic
      oligomers and aggregates by multiple disease-related proteins, including amyloid
      beta-protein (Abeta), whose self-assembly is believed to initiate brain
      pathogenesis in Alzheimer's disease. Lys residues play key roles in this process
      and participate in both types of interaction. They also are the target of our
      recently reported molecular tweezer inhibitors. To obtain further insight into
      the role of the two Lys residues in Abeta assembly and toxicity, here we
      substituted each by Ala in both Abeta40 and Abeta42 and studied the impact of the
      substitution on Abeta oligomerization, aggregation, and toxicity. Our data show
      that each substitution has a major impact on Abeta assembly and toxicity, with
      significant differences depending on peptide length (40 versus 42 amino acids)
      and the position of the substitution. In particular, Lys16->Ala substitution
      dramatically reduces Abeta toxicity. The data support the use of compounds
      targeting Lys residues specifically as inhibitors of Abeta toxicity and suggest
      that exploring the role of Lys residues in other disease-related amyloidogenic
      proteins may help understanding the mechanisms of aggregation and toxicity of
      these proteins.

PMID- 22860219
TI  - The delta opioid receptor agonist SNC80 selectively activates heteromeric MU
      delta opioid receptors.
AB  - Coexpressed and colocalized MU- and delta-opioid receptors have been established
      to exist as heteromers in cultured cells and in vivo. However the biological
      significance of opioid receptor heteromer activation is less clear. To explore
      this significance, the efficacy of selective activation of opioid receptors by
      SNC80 was assessed in vitro in cells singly and coexpressing opioid receptors
      using a chimeric G-protein-mediated calcium fluorescence assay, SNC80 produced a
      substantially more robust response in cells expressing MU-delta heteromers than
      in all other cell lines. Intrathecal SNC80 administration in MU- and delta-opioid
      receptor knockout mice produced diminished antinociceptive activity compared with
      wild type. The combined in vivo and in vitro results suggest that SNC80
      selectively activates MU-delta heteromers to produce maximal antinociception.
      These data contrast with the current view that SNC80 selectively activates delta
      opioid receptor homomers to produce antinociception. Thus, the data suggest that
      heteromeric MU-delta receptors should be considered as a target when SNC80 is
      employed as a pharmacological tool in vivo.

PMID- 22860217
TI  - DMH1, a highly selective small molecule BMP inhibitor promotes neurogenesis of
      hiPSCs: comparison of PAX6 and SOX1 expression during neural induction.
AB  - Recent successes in deriving human-induced pluripotent stem cells (hiPSCs) allow
      for the possibility of studying human neurons derived from patients with
      neurological diseases. Concomitant inhibition of the BMP and TGF-beta1 branches
      of the TGF-beta signaling pathways by the endogenous antagonist, Noggin, and the
      small molecule SB431542, respectively, induces efficient neuralization of hiPSCs,
      a method known as dual-SMAD inhibition. The use of small molecule inhibitors
      instead of their endogenous counterparts has several advantages including lower
      cost, consistent activity, and the maintenance of xeno-free culture conditions.
      We tested the efficacy of DMH1, a highly selective small molecule BMP-inhibitor
      for its potential to replace Noggin in the neuralization of hiPSCs. We compare
      Noggin and DMH1-induced neuralization of hiPSCs by measuring protein and mRNA
      levels of pluripotency and neural precursor markers over a period of seven days.
      The regulation of five of the six markers assessed was indistinguishable in the
      presence of concentrations of Noggin or DMH1 that have been shown to effectively
      inhibit BMP signaling in other systems. We observed that by varying the DMH1 or
      Noggin concentration, we could selectively modulate the number of SOX1 expressing
      cells, whereas PAX6, another neural precursor marker, remained the same. The
      level and timing of SOX1 expression have been shown to affect neural induction as
      well as neural lineage. Our observations, therefore, suggest that BMP-inhibitor
      concentrations need to be carefully monitored to ensure appropriate expression
      levels of all transcription factors necessary for the induction of a particular
      neuronal lineage. We further demonstrate that DMH1-induced neural progenitors can
      be differentiated into beta3-tubulin expressing neurons, a subset of which also
      express tyrosine hydroxylase. Thus, the combined use of DMH1, a highly specific
      BMP-pathway inhibitor, and SB431542, a TGF-beta1-pathway specific inhibitor,
      provides us with the tools to independently regulate these two pathways through
      the exclusive use of small molecule inhibitors.

PMID- 22860220
TI  - Metabolic multianalyte microphysiometry reveals extracellular acidosis is an
      essential mediator of neuronal preconditioning.
AB  - Metabolic adaptation to stress is a crucial yet poorly understood phenomenon,
      particularly in the central nervous system (CNS). The ability to identify
      essential metabolic events which predict neuronal fate in response to injury is
      critical to developing predictive markers of outcome, for interpreting CNS
      spectroscopic imaging, and for providing a richer understanding of the relevance
      of clinical indices of stress which are routinely collected. In this work, real
      time multianalyte microphysiometry was used to dynamically assess multiple
      markers of aerobic and anaerobic respiration through simultaneous electrochemical
      measurement of extracellular glucose, lactate, oxygen, and acid. Pure neuronal
      cultures and mixed cultures of neurons and glia were compared following a 90 min
      exposure to aglycemia. This stress was cytotoxic to neurons yet resulted in no
      appreciable increase in cell death in age-matched mixed cultures. The metabolic
      profile of the cultures was similar in that aglycemia resulted in decreases in
      extracellular acidification and lactate release in both pure neurons and mixed
      cultures. However, oxygen consumption was only diminished in the neuron enriched
      cultures. The differences became more pronounced when cells were returned to
      glucose-containing media upon which extracellular acidification and oxygen
      consumption never returned to baseline in cells fated to die. Taken together,
      these data suggest that lactate release is not predictive of neuronal survival.
      Moreover, they reveal a previously unappreciated relationship of astrocytes in
      maintaining oxygen uptake and a correlation between metabolic recovery of neurons
      and extracellular acidification.

PMID- 22860221
TI  - Benzothiazepine CGP37157 and its isosteric 2'-methyl analogue provide
      neuroprotection and block cell calcium entry.
AB  - Benzothiazepine CGP37157 is widely used as tool to explore the role of
      mitochondria in cell Ca(2+) handling, by its blocking effect of the mitochondria
      Na(+)/Ca(2+) exchanger. Recently, CGP37157 has shown to exhibit neuroprotective
      properties. In the trend to improve its neuroprotection profile, we have
      synthesized ITH12505, an isosteric analogue having a methyl instead of chlorine
      at C2' of the phenyl ring. ITH12505 has exerted neuroprotective properties
      similar to CGP37157 in chromaffin cells and hippocampal slices stressed with
      veratridine. Also, both compounds afforded neuroprotection in hippocampal slices
      stressed with glutamate. However, while ITH12505 elicited protection in SH-SY5Y
      cells stressed with oligomycin A/rotenone, CGP37157 was ineffective. In
      hippocampal slices subjected to oxygen/glucose deprivation plus reoxygenation,
      ITH12505 offered protection at 3-30 MUM, while CGP37157 only protected at 30 MUM.
      Both compounds caused blockade of Ca(2+) channels in high K(+)-depolarized SH
      SY5Y cells. An in vitro experiment for assaying central nervous system
      penetration (PAMPA-BBB; parallel artificial membrane permeability assay for blood
      brain barrier) revealed that both compounds could cross the blood-brain barrier,
      thus reaching their biological targets in the central nervous system. In
      conclusion, by causing a mild isosteric replacement in the benzothiazepine
      CGP37157, we have obtained ITH12505, with improved neuroprotective properties.
      These findings may inspire the design and synthesis of new benzothiazepines
      targeting mitochondrial Na(+)/Ca(2+) exchanger and L-type voltage-dependent
      Ca(2+) channels, having antioxidant properties.

PMID- 22860222
TI  - Multicolor fluorescence imaging of traumatic brain injury in a cryolesion mouse
      model.
AB  - Traumatic brain injury is characterized by initial tissue damage, which then can
      lead to secondary processes such as cell death and blood-brain-barrier
      disruption. Clinical and preclinical studies of traumatic brain injury typically
      employ anatomical imaging techniques and there is a need for new molecular
      imaging methods that provide complementary biochemical information. Here, we
      assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794,
      to detect cell death in a brain cryolesion mouse model that replicates certain
      features of traumatic brain injury. In short, the model involves brief contact of
      a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole
      body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in
      the living animal. Ex vivo imaging and histological analysis confirmed PSS-794
      localization to site of brain cell death. The nontargeted, deep-red Tracer-653
      was validated as a tracer dye for monitoring blood-brain-barrier disruption, and
      a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of
      cell death and blood-brain-barrier permeability in a single animal. The imaging
      data indicates that at 3 days after brain cryoinjury the amount of cell death had
      decreased significantly, but the integrity of the blood-brain-barrier was still
      impaired; at 7 days, the blood-brain-barrier was still three times more permeable
      than before cryoinjury.

PMID- 22860223
TI  - Exploration of synthetic approaches and pharmacological evaluation of PNU-69176E
      and its stereoisomer as 5-HT2C receptor allosteric modulators.
AB  - Allosteric modulators of the serotonin (5-HT) 5-HT(2C) receptor (5-HT(2C)R)
      present a unique drug design strategy to augment the response to endogenous 5-HT
      in a site- and event-specific manner with great potential as novel central
      nervous system probes and therapeutics. To date, PNU-69176E is the only reported
      selective positive allosteric modulator for the 5-HT(2C)R. For the first time, an
      optimized synthetic route to readily access PNU-69176E (1) and its diastereomer 2
      has been established in moderate to good overall yields over 10 steps starting
      from commercially available picolinic acid. This synthetic approach not only
      enables a feasible preparation of a sufficient amount of 1 for use as a reference
      compound for secondary pharmacological studies, but also provides an efficient
      synthesis of key intermediates to develop novel and simplified 5-HT(2C)R
      allosteric modulators. Compound 1 and its diastereomer 2 were functionally
      characterized in Chinese hamster ovary (CHO) cells stably transfected with the 5
      HT(2C)R using an intracellular calcium (Ca(i) (2+)) release assay. Compound 1
      demonstrated efficacy and potency as an allosteric modulator for the 5-HT(2C)R
      with no intrinsic agonist activity. Compound 1 did not alter 5-HT-evoked Ca(i)
      (2+) in CHO cells stably transfected with the highly homologous 5-HT(2A)R. In
      contrast, the diastereomer 2 did not alter 5-HT-evoked Ca(i) (2+) release in 5
      HT(2A)R-CHO or 5-HT(2C)R-CHO cells or exhibit intrinsic agonist activity.

PMID- 22860224
TI  - Small molecule screening identifies regulators of the transcription factor
      DeltaFosB.
AB  - DeltaFosB protein accumulates in the striatum in response to chronic
      administration of drugs of abuse, L-DOPA, or stress, triggering long lasting
      neural and behavioral changes that underlie aspects of drug addiction, abnormal
      involuntary movements (dyskinesia), and depression. DeltaFosB binds AP-1 DNA
      consensus sequences found in promoters of many genes and can both repress or
      activate gene transcription. In the striatum, DeltaFosB is thought to dimerize
      with JunD to form a functional transcription factor, though strikingly JunD does
      not accumulate in parallel. One explanation is that DeltaFosB can recruit
      different partners, including itself, depending on the neuron type in which it is
      induced and the chronic stimulus, generating protein complexes with different
      effects on gene transcription. To develop chemical probes to study DeltaFosB, a
      high-throughput screen was carried out to identify small molecules that modulate
      DeltaFosB function. Two compounds with low micromolar activity, termed C2 and C6,
      disrupt the binding of DeltaFosB to DNA via different mechanisms, and in in vitro
      assays stimulate DeltaFosB-mediated transcription. In cocaine-treated mice, C2
      significantly elevates mRNA levels of the AMPA glutamate receptor GluR2 subunit
      with specificity, a known target gene of DeltaFosB that plays a role in drug
      addiction and endogenous resilience mechanisms. C2 and C6 show different
      activities against DeltaFosB homodimers compared to DeltaFosB/JunD heterodimers,
      suggesting that these compounds can be used as probes to study the contribution
      of different DeltaFosB-containing complexes on the regulation of gene
      transcription in biological systems and to assess the utility of DeltaFosB as a
      therapeutic target.

PMID- 22860225
TI  - Coupling hippocampal neurogenesis to brain pH through proneurogenic small
      molecules that regulate proton sensing G protein-coupled receptors.
AB  - Acidosis, a critical aspect of central nervous system (CNS) pathophysiology and a
      metabolic corollary of the hypoxic stem cell niche, could be an expedient trigger
      for hippocampal neurogenesis and brain repair. We recently tracked the function
      of our isoxazole stem cell-modulator small molecules (Isx) through a chemical
      biology-target discovery strategy to GPR68, a proton (pH) sensing G protein
      coupled receptor with no known function in brain. Isx and GPR68 coregulated
      neuronal target genes such as Bex1 (brain-enriched X-linked protein-1) in
      hippocampal neural progenitors (HCN cells), which further amplified GPR68
      signaling by producing metabolic acid in response to Isx. To evaluate this
      proneurogenic small molecule/proton signaling circuit in vivo, we explored GPR68
      and BEX1 expression in brain and probed brain function with Isx. We localized
      proton-sensing GPR68 to radial processes of hippocampal type 1 neural stem cells
      (NSCs) and, conversely, localized BEX1 to neurons. At the transcriptome level,
      Isx demonstrated unrivaled proneurogenic activity in primary hippocampal NSC
      cultures. In vivo, Isx pharmacologically targeted type 1 NSCs, promoting
      neurogenesis in young mice, depleting the progenitor pool without adversely
      affecting hippocampal learning and memory function. After traumatic brain injury,
      cerebral cortical astrocytes abundantly expressed GPR68, suggesting an additional
      role for proton-GPCR signaling in reactive astrogliosis. Thus, probing a novel
      proneurogenic synthetic small molecule's mechanism-of-action, candidate target,
      and pharmacological activity, we identified a new GPR68 regulatory pathway for
      integrating neural stem and astroglial cell functions with brain pH.

PMID- 22860226
TI  - Oxidative stress effect of dopamine on alpha-synuclein: electroanalysis of
      solvent interactions.
AB  - The interaction of dopamine (DA) and alpha-synuclein (alpha-S) can lead to
      protein misfolding and neuronal death triggered by oxidative stress relevant to
      the progression of Parkinson's disease (PD). In this study, interfacial
      properties associated with DA-induced alpha-S aggregation under various solution
      conditions (i.e., pH, ionic strength) were investigated in vitro. The
      electrochemical oxidation of tyrosine (Tyr) residues in alpha-S was detected in
      the presence of DA. DA concentration dependence was analyzed and found to
      significantly affect alpha-S aggregation pathways. At low pH, DA was shown to be
      stable and produced no observable difference in interfacial properties. Between
      pH 7 and 11, DA promoted alpha-S aggregation. Significant differences in
      oxidation current signals in response to high pH and ionic strength suggested the
      importance of initial interactions in the stabilization of toxic oligomeric
      structures and subsequent off-pathways of alpha-S. Our results demonstrate the
      importance of solution interactions with alpha-S and the unique information that
      electrochemical techniques can provide for the investigation of alpha-S
      aggregation at early stages, an important step toward the development of future
      PD therapeutics.

PMID- 22860227
TI  - Total synthesis of diazonamide A.
AB  - A total synthesis of the marine natural product diazonamide A (1) has been
      accomplished. This work features a highly stereoselective synthesis of the C(10)
      quaternary center and the central furanoindoline core enabled by an iminium
      catalyzed alkylation-cyclization cascade. Additionally, a magnesium-mediated
      intramolecular macroaldolization and a palladium-catalyzed tandem
      borylation/annulation were developed to enable the closure of the two 12-membered
      macrocycles of diazonamide A. This synthesis involves 20 steps in its longest
      linear sequence and proceeds in 1.8% overall yield.

PMID- 22860228
TI  - Oncogenic signaling by tyrosine kinases of the SRC family in advanced colorectal
      cancer.
AB  - The non-receptor tyrosine kinases of the SRC family (SFK) play important roles in
      signal transduction induced by a large variety of extracellular stimuli,
      including growth factors and Integrins. When deregulated, SFKs show oncogenic
      activity, as originally reported for v-Src, the transforming product of the avian
      retrovirus RSV, and then, in many human cancers, particularly colorectal cancer
      (CRC). In CRC, SFK deregulation largely occurs in the absence of mutations of the
      corresponding genes, but the underlying molecular mechanisms involved are still
      unclear. In addition to a role in early tumor progression, SFK deregulation may
      also be important in advanced CRC, as suggested by the association between
      increased SFK activity and poor clinical outcome. However, SFK contribution to
      CRC metastasis formation is still poorly documented. Here, we will review recent
      findings that broaden our understanding of the mechanisms underlying SFK
      deregulation and signaling in advanced CRC. We will also discuss the implication
      of these observations for SFK-based therapy in metastatic CRC.

PMID- 22860229
TI  - The diverse and complex roles of radiation on cancer treatment: therapeutic
      target and genome maintenance.
AB  - Cancer is a genetic disease, grows exponentially with the development of
      intrinsic and acquired treatment resistance. Past decade has witnessed a
      considerable progress towards the treatment and understanding of proposed
      hallmarks of cancer and together with advances in early detection and various
      treatment modalities. Radiation therapy is an integral part of cancer treatment
      armamentarium. In developed countries more than half of all cancer patients
      receive radiation therapy during their course of illness. Although radiation
      damages both cancer and normal cells, the goal of radiation therapy is to
      maximize the radiation dose to abnormal cancer cells while minimizing exposure to
      normal cells, which is adjacent to cancer cells or in the path of radiation. In
      recent years, life expectancy increases among cancer patients and this increase
      is due to the results of early diagnosis, screening efforts, improved treatments
      and with less late effects mostly secondary cancer development. Therefore, cancer
      survivorship issues have been gaining prominence in the area of radiation
      oncology research. Understanding the tradeoff between the expected decreases in
      normal tissue toxicity resulting from an improved radiation dose distribution to
      the targeted site is an increasingly pertinent, yet needed attention and research
      in the area of radiation oncology. In recent years, a number of potential
      molecular targets that involve either with radiation increased tumor cell killing
      or protecting normal cells have been identified. For clinical benefits,
      translating these findings to maximize the toxicity of radiation on tumor cells
      while safeguarding early or late normal cell toxicities using molecular targeted
      radioprotectors will be useful in radiation treatment.

PMID- 22860230
TI  - Autophagy in pancreatic cancer pathogenesis and treatment.
AB  - Pancreatic cancer is the fourth most common cancer to cause death due to advanced
      stage at diagnosis and poor response to current treatment. Autophagy is the
      lysosome-mediated degradation pathway which plays a critical role in cellular
      defense, quality control, and energy metabolism. Targeting autophagy is now an
      exciting field for translational cancer research, as autophagy dysfunction is
      among the hallmarks of cancer. Pancreatic tumors have elevated autophagy under
      basal conditions when compared with other epithelial cancers. This review
      describes our current understanding of the interaction between autophagy and
      pancreatic cancer development, including risk factors (e.g., pancreatitis,
      smoking, and alcohol use), tumor microenvironment (e.g., hypoxia and stromal
      cells), and molecular biology (e.g., K-Ras and p53) of pancreatic cancer. The
      importance of the HMGB1-RAGE pathway in regulation of autophagy and pancreatic
      cancer is also presented. Finally, we describe current studies involving
      autophagy inhibition using either pharmacological inhibitors (e.g., chloroquine)
      or RNA interference of essential autophagy genes that regulate chemotherapy
      sensitivity in pancreatic cancer. Summarily, autophagy plays multiple roles in
      the regulation of pancreatic cancer pathogenesis and treatment, although the
      exact mechanisms remain unknown.

PMID- 22860231
TI  - When autophagy meets cancer through p62/SQSTM1.
AB  - Although p62/SQSTM1 was initially identified as an essential mediator of NFkappaB
      signaling, several recent studies have also highlighted its important role at the
      crossroad between the mTOR or MAPK signaling pathways and selective autophagy.
      The p62 structure containing important interaction domains attests to the ability
      of this protein to regulate and modulate the activation of these signaling
      pathways during tumor formation and propagation. The second very important
      function of this protein is to act as a molecular adaptor between the autophagic
      machinery and its substrates. Consequently, p62 is degraded following an increase
      in autophagic flux for which this protein currently serves as an indicator.
      However, the measurement of p62 expression strictly as a marker of autophagic
      flux is still controversial and can be misinterpreted mainly because this protein
      is subject to complex regulation at both the transcriptional and post
      translational levels. Finally, because p62 is an autophagic substrate, it acts as
      a molecular link between cancer and autophagy by conferring a high level of
      selectivity through the degradation of important signaling molecules.

PMID- 22860232
TI  - MicroRNAs in cancer treatment and prognosis.
AB  - Disturbances in microRNA expression by epigenetic alterations and mutations may
      promote not only tumorigenesis but also tumor aggressiveness, invasion,
      metastasis, and resistance to chemotherapy and radiotherapy. Several studies have
      profiled microRNA expression in normal and tumorigenic tissues, demonstrating a
      unique microRNA signature, which can be used as a marker for cancer diagnosis and
      prognosis. This review discusses the importance of microRNAs as regulatory
      biomolecules involved in cancer, focusing on microRNAs related to cancer
      invasion, metastasis, epigenetic alterations, chemoresistance, and
      radioresistance. The identification of both differentially expressed microRNAs in
      tumors and their target genes provides new tools for gene therapy; the re
      expression of microRNAs silenced by cancer development or the silencing of
      oncogenic microRNAs can be effective in the blockade of cancer-related cell
      proliferation.

PMID- 22860233
TI  - Androgen receptor as a targeted therapy for breast cancer.
AB  - Breast cancer occurs at a high frequency in women and, given this fact, a primary
      focus of breast cancer research has been the study of estrogen receptor alpha
      (ER) signaling. However, androgens are known to play a role in normal breast
      physiology and therefore androgen receptor (AR) signaling is becoming
      increasingly recognized as an important contributor towards breast
      carcinogenesis. Moreover, the high frequency of AR expression in breast cancer
      makes it an attractive therapeutic target, but the ability to exploit AR for
      therapy has been difficult. Here we review the historical use of androgen/anti
      androgen therapies in breast cancer, the challenges of accurately modeling
      nuclear hormone receptor signaling in vitro, and the presence and prognostic
      significance of AR in breast cancer.

PMID- 22860234
TI  - Pharmacology and anti-tumor activity of RWJ67657, a novel inhibitor of p38
      mitogen activated protein kinase.
AB  - Endocrine therapy resistance is a primary cause of clinical breast cancer
      treatment failure. The p38 mitogen activated protein kinase (MAPK) signaling
      pathway is known to promote ligand independent tumor growth and resistance to
      endocrine therapy. In this study, we investigated the therapeutic potential of
      the p38 inhibitor RWJ67657 in the treatment of tamoxifen resistant MDA-MB-361
      cells. RWJ67657 dose-dependently decreased both basal and stimulated activation
      of p38 MAPK signaling in this drug resistant cell system. Decreased activation of
      p38 by RWJ67657 resulted in inhibition of the downstream p38 targets hsp27 and
      MAPKAPK. Diminished p38 signaling resulted in inhibition of p38-medated gene
      transcription. Furthermore, pharmacological inhibition of p38 by RWJ67657
      decreased biological effects of p38, including ER-mediated gene expression and
      clonogenic survival in a dose-dependent manner. Animal studies revealed
      significantly decreased p38 signaling in vivo following exposure to RWJ67657.
      Treatment with the inhibitor markedly decreased phosphorylation of p38 in MDA-MB
      361 tumors, leading to decreased transcription of both Fra-1 and progesterone
      receptor. Utilizing well-established xenograft tumor models, we demonstrated that
      RWJ67657 exhibits potent anti-tumor properties. Treatment with RWJ67657 markedly
      decreased tamoxifen resistant tumor growth, both in the presence and absence of
      estrogen. Taken together, our findings demonstrate the therapeutic potential of
      targeting the p38-MAPK signaling cascade in the treatment of endocrine resistant
      breast cancer.

PMID- 22860235
TI  - Notch receptor inhibition reveals the importance of cyclin D1 and Wnt signaling
      in invasive esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive forms of
      squamous cell carcinomas. Common genetic lesions in ESCC include p53 mutations
      and EGFR overexpression, both of which have been implicated in negative
      regulation of Notch signaling. In addition, cyclin D1 is overexpressed in ESCC
      and can be activated via EGFR, Notch and Wnt signaling. To elucidate how these
      genetic lesions may interact during the development and progression of ESCC, we
      tested a panel of genetically engineered human esophageal cells (keratinocytes)
      in organotypic 3D culture (OTC), a form of human tissue engineering. Notch
      signaling was suppressed in culture and mice by dominant negative Mastermind
      like1 (DNMAML1), a genetic pan-Notch inhibitor. DNMAML1 mice were subjected to 4
      Nitroquinoline 1-oxide-induced oral-esophageal carcinogenesis. Highly invasive
      characteristics of primary human ESCC were recapitulated in OTC as well as
      DNMAML1 mice. In OTC, cyclin D1 overexpression induced squamous hyperplasia.
      Concurrent EGFR overexpression and mutant p53 resulted in transformation and
      invasive growth. Interestingly, cell proliferation appeared to be regulated
      differentially between those committed to squamous-cell differentiation and those
      invading into the stroma. Invasive cells exhibited Notch-independent activation
      of cyclin D1 and Wnt signaling. Within the oral-esophageal squamous epithelia,
      Notch signaling regulated squamous-cell differentiation to maintain epithelial
      integrity, and thus may act as a tumor suppressor by preventing the development
      of a tumor-promoting inflammatory microenvironment.

PMID- 22860236
TI  - Annexin 1 and its evolving role in systemic carcinogenesis besides its role in
      the pathogenesis of breast carcinomas.

PMID- 22860238
TI  - Body dysmorphic disorder and eating disorders in elite professional female ballet
      dancers.
AB  - BACKGROUND: Our objective is to report the prevalence and the clinical features
      associated with body dysmorphic disorder (BDD) and eating disorders (ED) in a
      group of elite Brazilian professional female ballet dancers. METHODS: Thirty-five
      elite Brazilian professional female ballet dancers were invited to participate in
      the study and 19 agreed to be assessed. Individuals were evaluated with a series
      of instruments, including the Mini International Neuropsychiatric Interview
      supplemented by the somatoform and eating disorders modules of the Structured
      Clinical Interview for DSM-IV disorders, the Bulimic Investigatory Test, and the
      Beck Depression Inventory. RESULTS: Three dancers (15.78%) had a lifetime
      diagnosis of anorexia nervosa (restrictive subtype) and 2 others (10.52%)
      presented a current diagnosis of BDD. No individuals had current or lifetime
      bulimia nervosa. Results could not be ascribed to comorbid major depression or
      increased severity of depression. CONCLUSION: The lifetime prevalence of BDD and
      ED among elite professional female ballet dancers was higher than the general
      population. High standards of beauty, public body exposure, and repeated exposure
      to mirrors in the rehearsal rooms may contribute to the development of body image
      disorders in this sample.

PMID- 22860239
TI  - Does the diagnosis of multiple Axis II disorders have clinical significance?
AB  - BACKGROUND: A stated goal of the DSM-5 Work Group on Personality and Personality
      Disorders (PDs) has been to reduce the high rate of comorbidity among PDs. Few
      studies have examined whether the diagnosis of multiple PDs has clinical
      significance. In the present report from the Rhode Island Methods to Improve
      Diagnostic Assessment and Services project, we tested the hypothesis that
      patients with >1 DSM-IV PD would have more severe forms of psychopathology than
      patients who were diagnosed with only 1 DSM-IV PD. METHODS: A total of 2,150
      psychiatric outpatients were evaluated with semi-structured diagnostic interviews
      for DSM-IV Axis I and Axis II disorders and measures of psychosocial morbidity.
      RESULTS: For 8 of the 10 PDs, the majority of patients had at least 1 additional
      PD, although at least 20% of patients diagnosed with each PD were diagnosed with
      only 1 PD. Compared with patients with 1 PD, patients with >=2 PDs had
      significantly more psychosocial morbidity. CONCLUSIONS: The co-occurrence of PDs
      conveys clinically significant information. Moreover, despite high levels of
      comorbidity, each PD also existed as a stand-alone entity. These findings raise
      questions about the DSM-5 Work Group's emphasis on reducing comorbidity in Axis
      II.

PMID- 22860237
TI  - Cell Models for the Study of Sex Steroid Hormone Neurobiology.
AB  - To date many aspects of neurons and glia biology remain elusive, due in part to
      the cellular and molecular complexity of the brain. In recent decades, cell
      models from different brain areas have been established and proven invaluable
      toward understanding this complexity. In the field of steroid hormone
      neurobiology, an important question is: what is the profile of steroid hormone
      receptor expression in these specific cell lines? Currently, a clear summary of
      such receptor profiling is lacking. For this reason, we summarized in this review
      the expression of estrogen, progesterone, and androgen receptors in several
      widely used cell lines (glial and neuronal) derived from the forebrain and
      midbrain, based on our own data and that from the literature. Such information
      will aid in the selection of specific cell lines used to test hypotheses related
      to the biology of estrogens, progestins, and/or androgens.

PMID- 22860240
TI  - Risk factors for delirium in patients undergoing hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Delirium is common after hematopoietic stem cell transplantation
      (HSCT) and is associated with increased morbidity and mortality. Early
      recognition and treatment have been shown to improve long-term outcomes. We
      sought to investigate the relationship between potential risk factors and the
      development of delirium following HSCT. METHODS: Fifty-four inpatients admitted
      for HSCT were assessed prospectively for delirium every 2 to 3 days during their
      inpatient stay using standardized delirium and neuropsychological measures. Self
      reports of medical history, medical records, and neurocognitive and psychiatric
      assessments were used to identify risk factors. Both pre- and post-HSCT risk
      factors were examined. RESULTS: Delirium incidence was 35% and occurred with
      highest frequency in the 2 weeks following transplant. The only pre
      transplantation risk factor was lower oxygen saturation (P = .003). Post
      transplantation risk factors for delirium included higher creatinine (P < .0001),
      higher blood urea nitrogen levels (P = .005), lower creatinine clearance (P =
      .0006), lower oxygen saturation (P = .001), lower hemoglobin (P = .04), and lower
      albumin (P = .03). There was no observed association with level of cognitive
      performance, transplant type, disease severity, medical comorbidity index, age,
      or conditioning regimen. CONCLUSIONS: Routine laboratory values can assist in the
      identification of high-risk patients before delirium onset to improve early
      detection and treatment of delirium after HSCT.

PMID- 22860241
TI  - The effects of mirtazapine on sleep in patients with major depressive disorder.
AB  - BACKGROUND: Mirtazapine is a commonly used antidepressant with a well-known
      ability to produce sedation. At the same time, its sleep-promoting effects in
      patients with major depressive disorder (MDD) are relatively unclear. The purpose
      of this article is to provide clinicians with a detailed review of mirtazapine's
      sleep effects in patients with MDD. METHODS: A literature search was conducted
      for studies involving mirtazapine in depressed patients that specifically
      assessed sleep. RESULTS: Twenty-three studies met selection criteria and were
      included in this review. Of the 15 studies that included a general assessment of
      sleep, all noted improvement from baseline with mirtazapine. Twelve of the 23
      trials were randomized, blinded, and controlled. Mirtazapine was superior to
      placebo but did not clearly differentiate itself from other antidepressants, with
      the exception of venlafaxine. Eight studies used detailed measures of sleep and
      consistently reported that mirtazapine produced significant improvement in sleep
      efficiency, total sleep time, and sleep quality. Few investigations combined
      detailed assessments of sleep along with a comparator antidepressant. CONCLUSION:
      Mirtazapine is an antidepressant with sleep-promoting effects significantly
      greater than placebo, similar to tricyclic antidepressants, and somewhat similar
      to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake
      inhibitors. These effects must be balanced with mirtazapine's ability to cause
      sedation-related side effects.

PMID- 22860242
TI  - Second-generation antipsychotic use in schizophrenia and associated weight gain:
      a critical review and meta-analysis of behavioral and pharmacologic treatments.
AB  - BACKGROUND: Weight gain in schizophrenia, particularly secondary to second
      generation antipsychotic (SGA) use, is a common adverse effect and often is
      associated with significant physical and psychological morbidity. METHODS: We
      performed a critical literature review of all controlled clinical trials for
      pharmacologic and/or behavioral management of SGA-induced weight gain in
      schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis
      was performed to estimate and compare weight changes for various medications and
      behavioral interventions. RESULTS: Sample sizes generally were small. Clinical
      trials were 6 weeks to 1 year, and weight loss was modest with any treatment.
      Although several adjunctive pharmacologic treatments showed no weight loss,
      sibutramine, metformin, and topiramate showed some benefit. Amantadine and
      orlistat were somewhat less effective and had lower rates of tolerability. Among
      the behavioral therapies, nutritional counseling combined with exercise showed
      the most benefit. Behavioral therapies, although modest, showed the most
      consistent benefits compared with controls. CONCLUSIONS: Scheduled pharmacologic
      treatment to prevent weight gain or promote weight loss in schizophrenia patients
      on SGA therapy is limited based on current studies. Switching antipsychotic
      agents has not been established as a long-term solution. Additional long-term
      studies are required to influence clinical practice.

PMID- 22860243
TI  - Gabapentin for treating acquired neurogenic stuttering.

PMID- 22860244
TI  - Agomelatine for the treatment of posttraumatic stress disorder: a case report.

PMID- 22860245
TI  - The new European Journal of Preventive Cardiology.

PMID- 22860246
TI  - Species-genetic diversity correlations in habitat fragmentation can be biased by
      small sample sizes.
AB  - Predicted parallel impacts of habitat fragmentation on genes and species lie at
      the core of conservation biology, yet tests of this rule are rare. In a recent
      article in Ecology Letters, Struebig et al. (2011) report that declining genetic
      diversity accompanies declining species diversity in tropical forest fragments.
      However, this study estimates diversity in many populations through extrapolation
      from very small sample sizes. Using the data of this recent work, we show that
      results estimated from the smallest sample sizes drive the species-genetic
      diversity correlation (SGDC), owing to a false-positive association between
      habitat fragmentation and loss of genetic diversity. Small sample sizes are a
      persistent problem in habitat fragmentation studies, the results of which often
      do not fit simple theoretical models. It is essential, therefore, that data
      assessing the proposed SGDC are sufficient in order that conclusions be robust.

PMID- 22860249
TI  - Proceedings of the 15th Annual Meeting of the Society of Biotherapeutic
      Approaches, December 3, 2011, Fukuoka, Japan.

PMID- 22860248
TI  - Special issue in honor of Dr. Fantus.

PMID- 22860250
TI  - Advances in Chronic Kidney Disease 2011. Proceedings of the 14th International
      Conference on Dialysis. January 25-27, 2012, Palm Harbor, FL.

PMID- 22860251
TI  - Special issue in honor of Yoshiki Hotta.

PMID- 22860252
TI  - Breast cancer following diethylstilbestrol exposure in utero: a tragedy?

PMID- 22860253
TI  - Proceedings of a symposium: Smallpox Eradication after 30 Years: Lessons,
      Legacies and Innovations, August 24-27, 2010, Rio de Janeiro, Brazil.

PMID- 22860254
TI  - Proceedings of the Ninth Annual Research in Computational Molecular Biology
      (RECOMB) Satellite Workshop on Comparative Genomics, October 8-10, 2011, Galway,
      Ireland.

PMID- 22860255
TI  - Removal notice to: "A polymorphism in the 5' untranslated region of ERCC5
      determines effectiveness of platinum-based chemotherapeutics" [Toxicology 290
      (2011) 118].

PMID- 22860256
TI  - Special Issue on Pharmacogenetics is dedicated to the memory of Professor Robert
      W Kerwin.

PMID- 22860257
TI  - Development and validation of an LC-MS-MS method for determination of methyl
      kulonate in rat plasma.
AB  - A sensitive, rapid and specific LC-MS-MS method was established and validated for
      determination of methyl kulonate, a major bioactive constituent isolated from
      Meliae Cortex, in rat plasma. Plasma samples were treated by precipitating
      protein with methanol and were chromatographed using a Capcell Pak C18 column
      (100 x 4.6 mm, 5 MUm) with the mobile phase comprising a mixture of methanol, 10
      mM ammonium formate and formic acid (95:5:0.1, v/v/v). Detection and
      quantification were performed by mass spectrometry in the multiple reaction
      monitoring mode with positive atmospheric ionization at m/z 467 --> 311 for
      methyl kulonate, and m/z 469 --> 451 for dubione B (internal standard),
      respectively. A good linear response was observed over the concentration range
      1.00-500 ng/mL with the lower limit of quantification 1.00 ng/mL in rat plasma.
      The method also afforded satisfactory results base on sensitivity, specificity,
      precision, accuracy, recovery, freeze-thaw and long-time stability. The validated
      method was successfully applied to determine the pharmacokinetic properties of
      methyl kulonate in rats after oral administration at dose of 100 mg/kg. This
      pharmacokinetic study of methyl kulonate is reported here for the first time.

PMID- 22860258
TI  - Characterization of multiple absorbed constituents in rats after oral
      administration of Paederia scandens decoction.
AB  - Paederia scandens (Lour.) Merri. (Jishiteng in Chinese) is a Chinese traditional
      medicine widely used in treating various diseases. However, its active components
      have remained unknown. In the present study, a rapid and sensitive method by high
      performance liquid chromatography coupled with electrospray ionization mass
      spectrometry (HPLC-MSn) techniques was employed to investigate the absorbed
      constituents in rats after oral administration of Paederia scandens decoction. By
      comparing their MS data with those of authentic compounds and published data, a
      total of six compounds (paederosid, 1; paederosidic acid, 2; paederosidic acid
      methyl ester, 3; 6-hydroxy geniposide, 4; asperuloside, 5; and deacetyl
      asperuloside, 6) were identified in the P. scandens decoction samples. In
      addition, a total of seven compounds, including three iridoid glucosides and four
      of their metabolites, were identified in rat urine samples after administration.
      In addition, six compounds, including four iridoid glucosides and two of their
      metabolites, were identified in rat serum samples after administration. Our
      results significantly narrow the range of potentially active compounds in P.
      scandens decoction, and build a solid foundation for future research on its
      mechanism.

PMID- 22860259
TI  - Dealing with the pressure of expectation!

PMID- 22860260
TI  - A patient with positional vertigo.

PMID- 22860261
TI  - A 60-year-old woman with rapidly progressive memory loss.

PMID- 22860262
TI  - An interview with Jen Sheen.

PMID- 22860263
TI  - Preparing for conferences--basic presentation skills.

PMID- 22860264
TI  - Battle hardened.

PMID- 22860265
TI  - Transitioning to a physician scientist.

PMID- 22860266
TI  - Math aversion.

PMID- 22860267
TI  - Cardiac tamponade: atypical presentations after cardiac surgery.
AB  - We present two cases of cardiac tamponade presenting in the aftermath of cardiac
      surgery. We have briefly discussed the aetiology, presentation, diagnosis and
      management of the condition with emphasis on its atypical presentation in
      postoperative patients. A high index of suspicion and early access to
      echocardiography is necessary for prompt recognition and treatment of this life
      threatening emergency.

PMID- 22860268
TI  - Effect of complete extraction and re-addition of manganese on thermoluminescence
      of pea Photosystem II preparations.
AB  - Thermoluminescence of Photosystem II particles isolated from pea chloroplasts
      using digitonin and Triton X-100 was measured after 1 min illumination at a
      certain temperature (T(ex)) followed by illumination during cooling (40 Cdeg/min)
      to a lower temperature. Glow curves of the particles are characteristic of the
      photosynthetic oxygen-evolving material studied earlier. Complete (more than 95%)
      removal of Mn from the Photosystem II particles abolishes thermoluminescence
      bands around 0 degrees  C, related to the oxygen-evolving system, but the
      thermoluminescence bands peaking around -30 degrees C (TL(-30)), -55 degrees C
      (TL_ (-55)) and between-68 and -85 degrees  C, depending on Tex(TLv), remain
      unaltered. The bands are characterized by different dependence on T,x. The TL(
      30), TL(-55) and TL v bands can also be observed in the glow curve of isolated
      pea and spinach chloroplasts. Re-addition of MnCI (2) (2 MUM, corresponding to
      nearly 4 Mn atoms per reaction center of Photosystem II) to the Mn-depleted
      particles does not reactivate the thermoluminescence bands around 0 degrees  C.
      However, it does lead to suppression of TL(-30) accompanied by parallel
      activation of TL(-55), revealing competition of the TL (-30) and TL(-55) for
      charges generated by the reaction center. These data, as well as the results on
      the effect of inhibitors and electron donors to Photosystem II, show that
      positive charges contributing to the TL(-30), TL (-55) and TL v
      thermoluminescence bands are located on secondary electron donors of Photosystem
      II which do not require Mn and are located closer to the reaction center than the
      Mn-containing, water-oxidizing enzyme.

PMID- 22860269
TI  - How safe is your hospital? Our new ratings find that too many pose risks.

PMID- 22860270
TI  - Sleep tighter: our survey of 26,451 readers finds insomnia rampant but treatable.

PMID- 22860272
TI  - [Screening laboratory tests for patients at high risk for atherosclerosis: are
      there any difference in clinical significance among them?--Chairman's
      introductory remarks].

PMID- 22860273
TI  - [Medical support and laboratory testing in developing countries: Chairman's
      introductory remarks].

PMID- 22860274
TI  - [Environmental factors that influence the pathophysiology of mental disorders in
      various life stages and the design of molecular- targeting drugs for these
      disorders].

PMID- 22860275
TI  - From Ayn Rand to Ron Paul.

PMID- 22860276
TI  - Tanning themselves to death: a new teen fad.
AB  - Incidence rates of melanoma continue to rise, especially in young women, despite
      the enormous body of evidence that identifies ultraviolet radiation as a skin
      carcinogen. It is time for a change in societal norms, an increase in counseling
      of young adults about the risks of indoor tanning facilities, and to prevent
      young adults from tanning by introducing new legislation.

PMID- 22860277
TI  - The Joplin Tornado: recovery one year later.
AB  - The death and destruction caused by the deadliest single tornado in Missouri's
      history was indescribable.

PMID- 22860278
TI  - Preparedness is the key.

PMID- 22860279
TI  - Why me? Why now? Why prepare for sudden misfortune?

PMID- 22860280
TI  - Part I--Special from Missouri Physicians Health Program. Sexual misconduct by
      professionals: a new paradigm of understanding.

PMID- 22860281
TI  - Part II--Sexual misconduct by professionals. Safeguarding yourself and your
      practice against allegations of sexual abuse or patient impropriety.
AB  - By drawing boundaries between their personal and professional lives, physicians
      can protect their practices and themselves while also still achieving their true
      goal: providing quality care to their patients.

PMID- 22860282
TI  - When vigorous exercise becomes too much of a good thing.

PMID- 22860283
TI  - The give and take of good patient communication. A visit to the doctor.

PMID- 22860284
TI  - Pradaxa, bleeding and tort litigation solicitation.

PMID- 22860285
TI  - Role of CT calcium scoring in screening for coronary artery disease.

PMID- 22860286
TI  - Research from the bedside to the lab bench & back.
AB  - Transgenic mice represent a unique opportunity in biomedical research to discover
      the genes underlying disease and understand how manipulating the function of
      single genes and proteins alters physiology in a whole animal system. These
      advances in biomedical research may accelerate the time between when basic
      discoveries are made and when the research can be 'translated', that is, when the
      research will positively impact the lives of patients. The purpose of this
      article is to present some examples of promising mouse models of human diseases.

PMID- 22860287
TI  - The tale of mind & heart: psychiatric disorders & coronary heart disease.
AB  - The mind-body interaction has always intrigued humans. Most people, on the basis
      of either intuition or personal experience, believe that emotional stress can
      cause or alter the course of even major physical diseases. Sir William Osler
      described his typical patient with angina pectoris as 'a man whose engine is
      always set full speed ahead' and described his patients with cardiac disease as
      'worriers'. In recent years there has been tangible evidence for the existence of
      this interaction however modern medicine is still trying to unravel its
      intricacies. In this article we review the current knowledge regarding the effect
      of depression, anxiety disorders and the detrimental effect it has on coronary
      heart disease. In addition we discuss some of the proven acute psychological
      triggers for acute coronary syndrome.

PMID- 22860288
TI  - Nutritional and vitamin supplements: do they prevent coronary artery disease?
AB  - This article will review background information and data supporting the use of
      fish oil, folic acid, coenzyme Q, and vitamins C, D, and E in the prevention
      and/or treatment of coronary artery disease.

PMID- 22860289
TI  - The management of chronic diseases in rural Missouri practices.
AB  - This qualitative study describes the challenges of managing chronic diseases in
      small, rural, health care practices in Missouri. Four recurrent themes were
      identified from each of the nine focus groups: the similarity of their patient
      population and community characteristics, their unfamiliarity with aspects of the
      chronic care model, the consistent problem of poverty as a barrier to health care
      access for patients, and the uncertainty about what health care reform will mean
      for rural practice settings.

PMID- 22860290
TI  - Use of Angio-Seal after iatrogenic trauma.
AB  - The clinical and intraoperative findings of an iatrogenic injury to a
      congenitally present right sided ascending aorta treated by deployment of a
      percutaneous closure device is reported. This is a first literature report of a
      biodegradable closure system being utililized to treat a puncture to the
      ascending arch.

PMID- 22860291
TI  - State of the association: presidential address.

PMID- 22860292
TI  - Presidential inaugural address. K.I.S.S.

PMID- 22860293
TI  - [Changing perioperative scenes].

PMID- 22860294
TI  - [Usefulness and clinical application of phototherapy: preface and comments].
AB  - The following articles describe topics of phototherapy including low reactive
      laser therapy by diode laser device, semiconductor as a medium consisting of
      aluminum, gallium and arsenic, near infrared light irradiator using halogen lamp,
      and xenon light by high-intensity electrical stimulation of xenon gas. In
      addition, the applications of phototherapy in the clinical medicine such as
      rehabilitation, orthopedics and pain clinic are described. Phototherapy is a
      useful and safe method for pain relief.

PMID- 22860295
TI  - [Low reactive laser therapy].
AB  - The type, characteristics and effect of low reactive laser equipment used for
      pain treatment in Japan are described in this section. Currently, low reactive
      laser therapy equipments marketed and used in Japan include diode laser
      therapeutic device with semiconductor as a medium consisting of aluminum, gallium
      and arsenic. Low reactive laser equipment comes in three models, the first type
      has a capacity of generating 1,000 mW output, and the second type has a capacity
      of generating 10 W output. The third type has four channels of output, 60, 100,
      140 and 180 mW and we can select one channel out of the four channels. This model
      is also used as a portable device because of its light weight, and we can carry
      it to wards and to the outside of the hospital. Semiconductor laser has the
      capacity of deepest penetration and the effect tends to increase proportionally
      to the increasing output. Low reactive laser therapy is less invasive and lower
      incidence of complications. Although low reactive laser therapy might be
      effective for various pain disorders, the effect is different depending on the
      type of pain. We should keep in mind that this therapy will not give good pain
      relief equally in all patients with pain.

PMID- 22860296
TI  - [Near infrared light irradiator using halogen lamp].
AB  - The practical electric light bulb was invented by Thomas Alva Edison in 1879.
      Halogen lamp is the toughest and brightest electric light bulb. With light
      filter, it is used as a source of near infrared light. Super Lizer and Alphabeam
      are made as near infrared light irradiator using halogen lamp. The light emmited
      by Super Lizer is linear polarized near infrared light. The wave length is from
      600 to 1,600 nm and strongest at about 1,000 nm. Concerning Super Lizer, there is
      evidence of analgesic effects and normalization of the sympathetic nervous
      system. Super Lizer has four types of probes. SG type is used for stellate
      ganglion irradiation. B type is used for narrow area irradiation. C and D types
      are for broad area irradiation. The output of Alphabeam is not polarized. The
      wave length is from 700 to 1,600 nm and the strongest length is about 1,000nm.
      Standard attachment is used for spot irradiation. Small attachment is used for
      stellate ganglion irradiation. Wide attachment is used for broad area
      irradiation. The effects of Alphabeam are thought to be similar to that of Super
      Lizer.

PMID- 22860297
TI  - [Xenon light therapy].
AB  - The xenon light, generated by high-intensity electrical stimulation of xenon gas,
      is used to sterilize wounds, aid tissue repair, and relieve pain as a low-level
      light therapy. The light produced consists of non-coherent beams of multiple
      wavelengths in the ultraviolet to infrared spectrum. This broad-band light can be
      emitted in a continuous wave or pulsed mode, with the wave band chosen and the
      energy distribution controlled for the purpose. Specifically, wavelengths in the
      500-700 nm range are suitable for treating superficial tissue, and wavelengths
      between 800 and 1,000 nm are suitable for deeper-seated tissues, due to longer
      optical penetration distances through tissue. One of the most common benefits in
      the xenon light therapy is considered to be the wide and deep irradiation of
      optimal rays to living tissue. Research into the use of xenon light for tissue
      repair and pain reduction is restricted within open-label studies and case
      reports. The present review expounded the effects of xenon light therapy on the
      basis of the available evidence in vitro and in vivo studies using a laser beam
      of single wavelength.

PMID- 22860298
TI  - [Phototherapy in rehabilitation medicine].
AB  - Rehabilitation can be classified into four types: medical, vocational,
      educational, and social rehabilitation. The goal of medical rehabilitation is to
      maintain and improve a patient's physical and mental capabilities. Phototherapy
      is an important means of treatment in rehabilitation medicine and is usually
      performed with ultraviolet, infrared, or laser light. Among them, laser light has
      been shown to have various biological effects, such as increasing blood flow,
      promoting wound healing, reducing inflammation, and improving immune function.
      Laser therapy is as important a treatment option as exercise therapy in
      rehabilitation medicine, and is considered to be worth evaluating as a
      therapeutic means to relieve pain in musculoskeletal disorders, promote healing
      in peripheral neuropathy, and alleviate muscle spasticity.

PMID- 22860299
TI  - [Present and future for LLLT in the area of orthopedics].
AB  - The biological tissue is irradiated with laser light, and carbonization,
      incineration, evaporation, blood coagulation, protein denaturation, and
      photoactivation will arise in order of the strength of the reaction. LLLT is the
      application of those photoactivated biological effects. In this paper, effective
      pain relief, photoactivation effect on chondrocytes, and, PDT (photodynamic
      therapy) using photosensitizer are introduced.

PMID- 22860300
TI  - [Pain treatment with low reactive level laser therapy (LLLT)].
AB  - Noninvasive and low reactive level laser (LLLT) is used as one of the light
      therapies without giving pain to the patient. Therefore, it is used often
      clinically in pain treatment, orthopedics, plastic surgery, dermatology, and
      dentistry. In the pain clinic field, it is one of the procedures indispensable to
      treatment of various pain including postherpetic neuralgia, diabetic neuropathy
      or myofascial pain. In recent years the mechanism has been gradually elucidated
      by basic study. The action is on sensory nerve, sympathetic nerve, blood vessel,
      immunity, inflammation and central nervous system, and is thought to contribute
      to analgesia. Also, many reports such as action to inhibit "itch", a promotor
      action of the bone metabolism, and the follicular maturation acceleration action
      have tested and elucidated these mechanisms, and will add further adaptation that
      will be new in future. Furthermore, development and downsizing of the free
      electron laser will promote elucidation of the low response level laser therapy.
      We expect much in the future of the LLLT.

PMID- 22860301
TI  - [Comparison of usefulness of the dorsal branch of the radial artery with the
      radial artery for arterial cannulation].
AB  - BACKGROUND: The radial artery cannulation is often associated with damped
      arterial waveforms with the hand moving. We used cannulation of the dorsal branch
      of the radial artery (DRA) and compared the stability of measurement, safety and
      complications with those of the radial artery(RA). METHODS: The study was a
      prospective single-blinded comparative study. Seventy-six patients undergoing
      general anesthesia requiring arterial cannulation were included. Patients were
      divided randomly into two separate groups of 35 patients each according to
      cannulation site: the radial artery (RA group) or the dorsal branch of the radial
      artery (DRA group). After induction of general anesthesia, cannulation was
      performed. Three hours after the successful cannulation, the changes of waveforms
      were noted with the hand moving. We examined whether there were any complications
      around the cannulation site after cannula removal. RESULTS: With the wrist
      flexion at all angles (30, 60 and 90 degrees), the frequency of worsening of
      arterial waveforms was significantly higher in RA group compared with DRA group.
      Some difficulties in catheter placement were observed in DRA group. No
      concomitant complication was noticed. CONCLUSIONS: Arterial line monitoring from
      DRA had better waveforms compared with RA monitoring without any complications.

PMID- 22860302
TI  - [Anesthesia for electroconvulsive therapy -- comparison of propofol with
      sevoflurane].
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is performed under general anesthesia
      (GA). GA could reduce the vigorous hemodynamic response including hypertension
      and tachycardia during ECT. This may be beneficial in patients with
      cardiovascular diseases. On the other hand, however, many intravenous and
      inhalational anesthetic agents potentially suppress the seizure and shorten the
      duration. The aim of this study is to elucidate whether propofol is superior to
      sevoflurane in maintaining the duration of electroencephalographic (EEG) seizure
      evoked by Thymatron System while stabilizing hemodynamic responses. METHODS:
      Thirteen patients (male:female = 3:10) were included in this cross-over study.
      The patients underwent 54 ECT sessions in total. The sessions were randomized
      into two groups. In the propofol group (P group), the patients received
      intravenous propofol 1 mg x kg(-1) on induction of anesthesia, whereas those in
      the sevoflurane group (S group) were induced with sevoflurane at 5% inspired
      concentration. In either group, after loss of consciousness, the patients
      received 1 mg x kg(-1) of suxamethonium. When muscle fasciculation faded away,
      the electrostimulus was delivered. The duration of EEG seizure, heart rate (HR)
      and noninvasive mean arterial blood pressure (MAP) were recorded. RESULTS: The
      duration of EEG seizure was longer in P group (34.6 +/- 15.5 sec versus 23.6 +/-
      12.0 sec in S group, P = 0.006). There was no significant difference in
      hemodynamic parameters (MAP, HR) between the two groups. CONCLUSIONS: The
      duration of EEG seizure in ECT was significantly longer with propofol anesthesia
      than sevoflurane anesthesia. Propofol may provide more benefits than sevoflurane
      as the anesthetic for ECT.

PMID- 22860303
TI  - [Awake intubation using Pentax-airway scope combined with surface airway
      anesthesia in the cases of two obese patients with cervical spondylosis and the
      author himself].
AB  - We report successful awake intubation using AWS combined with surface anesthesia
      of the upper airway via nebulizer. The two cases are suitable for awake
      intubation due to difficult airway. After inhaled lidocaine 4% and nebulized 4
      ml, while giving fentanyl i. v, we performed awake intubation. As a preparatory
      step to the procedure described above, awake intubation was tested on the author
      himself with only surface anesthesia. The patients and author did not buck during
      intubation. The present case shows that it is possible to perform awake intubate
      safely with less stress with the combination of AWS and surface airway anesthesia
      via nebulizer.

PMID- 22860304
TI  - [Anesthetic management of a child with myotubular myopathy who underwent two
      operations using only total intravenous anesthesia (TIVA)].
AB  - We present a case of anesthetic management in a child with myotubular myopathy. A
      3-month-old, 3.0 kg, male patient, who had been suspected of a congenital
      myopathy, was scheduled for the muscle biopsy. He was intubated at birth in NICU.
      Anesthesia was induced with propofol and remifentanil, and maintained with
      propofol and remifentanil. The results of biopsy and gene analysis led to the
      diagnosis of myotubular myopathy. Five months later, this 8-month-old, 4.0 kg,
      patient was scheduled for the tracheostomy. Anesthesia was induced with propofol,
      fentanyl and rocuronium bromide, and maintained with propofol and fentanyl. The
      child underwent two operations under total intravenous anesthesia (TIVA) with
      propofol and fentanyl or remifentanil. These anesthetic courses were uneventful
      without symptoms of malignant hyperthermia nor propofol infusion syndrome. We did
      not use sugammadex, because there is still no evidence to the safe use of
      sugammadex in infants (aged 28 days-23 months). Congenital myopathy is related to
      malignant hyperthermia, and total intravenous anesthesia (TIVA) is a preferable
      and safe method for children with this disease.

PMID- 22860305
TI  - [Case of anaphylactic reaction caused by sugammadex].
AB  - A 17-year-old man was scheduled for ventriculo-peritoneal shunt under general
      anesthesia. Anesthesia was induced by propofol, rocuronium and pentazocine, and
      maintained with sevoflurane and nitrous oxide. The operation was finished in 1
      hour and 4 minutes without trouble. After the operation, sugammadex was
      administered. After about 2 minutes, the redness and the wheal appeared in the
      body trunk, and SpO2 dropped to The appearance of rapid symptom immediately after
      administration of sugammadex indicated that anaphylactic reaction had occurred.
      We administered adrenaline. After the administration of adrenaline several times,
      cutaneous findings became improved and SpO2 was stabilized. We started continuous
      infusion of adrenaline, and the patient was moved to the intensive care unit
      (ICU). Twelve hours after entering the ICU, the patient was extubated. He showed
      no troubles thereafter, and left hospital. After introduction of sugammadex to
      clinical use, 7 cases of anaphylactic reaction to sugammadex were reported. We
      must know that anaphylactic reaction can be induced by sugammadex.

PMID- 22860306
TI  - [Difficult ventilation after sugammadex administration: a case report].
AB  - A 71-year-old woman was scheduled for arthroscopic knee surgery. Anesthesia was
      administered with sevoflurane, fentanyl, and rocuronium bromide. Total dose of
      fentanyl was 200 microg and total dose of rocuronium bromide was 40mg. After
      surgery sugammadex 150 mg was given before awakening of the patient and
      appearance of spontaneous breathing. Immediately after the administration of
      sugammadex airway pressure increased to 37 cmH20, and ventilation became
      difficult. After naloxone 0.1 mg injection, ventilation improved dramatically.
      The cause of difficult ventilation was surmised to be upper airway reflex or
      muscle rigidity caused by reaction to fentanyl. We thought the phenomenon was
      clearly manifested by rapid recovery from muscle relaxation by injection of
      sugammadex. Before injection of sugammadex, it is necessary to confirm the
      effects of anesthetics on the patient's condition.

PMID- 22860308
TI  - [Anesthetic management of a patient with SAPHO syndrome: a case report].
AB  - We report a case of SAPHO syndrome accompanying progressive osteoarthritis. In
      this 43-year-old woman, difficult intubation was expected due to unilateral
      hyperostosis of the mandible and spinal degeneration. As far as we know,
      anesthetic management of this disease has not been reported. Therefore we made an
      anesthetic plan based on spinal degenerative disease which was considered to have
      similar problems of intubation and the case was managed without problems. As this
      syndrome is a progressive disorder, careful perioperative management is required
      each time.

PMID- 22860307
TI  - [Case of acute pain of herpes zoster with preceding immobility of the shoulder].
AB  - A 62-year-old-man treated for nephrotic syndrome with steroid developed acute
      pain of herpes zoster after immobility of the shoulder. Steroids might have
      suppressed the first symptoms of pain. But immobility probably appeared as VZV
      infection developing to spinal ventral root. Suprascapular nerve block was
      effective for severe pain of the right arm. Sympathetic nerve contained in
      suprascapular nerve might have been blocked. Sympathetically maintained pain may
      occur when primary afferent neurons are excited by inflammation due to VZV
      infection. Pain was abolished 17 weeks after the onset of rash using blocks three
      times and amitriptyrin and valproic acid. Immobility was resolved seven months
      after the onset of rash.

PMID- 22860309
TI  - [Case of fluminant myocarditis with fatal pulmonary edema even after introduction
      of bi-ventricular assist devices].
AB  - A 15-year-old man developed cardiopulmonary dysfunction 4 days after flu-like
      symptom, and was transfered to our hospital and diagnosed as a fulminant
      myocarditis (FM). Intraaortic ballon pumping (IABP) and percutaneous
      cardiopulmonary support (PCPS) were immediately initiated. However, cardiac
      function did not recover until 7 days after admission to the ICU, and bilateral
      ventricular assist devices (BiVAD) were introduced with extracorporeal membrane
      oxygenation (ECMO). Right ventricular assist device (RVAD) with ECMO was
      established by right atrial blood withdrawal and pulmonary arterial blood supply
      using centrifugal pump. After operation of BiVAD, to main LVAD flow, frequent
      blood-and-fluids volume loading and increase in RVAD flow were necessary due to
      postoperative bleeding and massive foamy sputum. However, even after hemostasis
      had been established, the pulmonary edema continued and it was difficult to
      maintain LVAD flow because of endless transudation from the lungs. Eventually, he
      developed MOF and passed away 9 days after the admission to ICU. As in cases of
      end-stage dilated cardiomyopathy, outflow of RVAD into the left atrium instead of
      the pulmonary artery was demonstrated effective in avoiding trans-pulmonary
      leakage, and outflow of RVAD into the left atrium may be beneficial to patients
      with FM who need BiVAD but suffered severe pulmonary edema.

PMID- 22860311
TI  - [General anesthesia in a orthopedic case with the Kommerell's diverticulum of
      right-sided aortic arch diagnosed on preoperative examination].
AB  - Kommerell's diverticulum is a rare anomaly of the aortic arch. A 59-year-old man
      was scheduled for open reduction and internal fixation of his right proximal
      tibial fracture under general anesthesia. We diagnosed right-sided aortic arch by
      the chest X-ray and thoracic computed tomography. His trachea and esophagus were
      compressed by the aortic arch. He had complained of no dyspnea or dysphagia.
      Respiratory difficulty might be caused by muscle relaxants, intermittent positive
      pressure ventilation, change of intrathoracic pressure, postural change and
      overloaded infusion during general anesthesia in a case of right-sided aortic
      arch. We performed lumbar epidural anesthesia and inserted an i-gel after general
      anesthesia induction preserving spontaneous respiration in preparation for
      controlled ventilation or tracheal intubation via an i-gel. We could accomplish
      the operation uneventfully and he was discharged on POD 53. A supraglottic airway
      such as an i-gel was a useful device in the present case of right-sided aortic
      arch with Kommerell's diverticulum.

PMID- 22860310
TI  - [Anesthetic management of a patient with paroxysmal nocturnal hemoglobinuria].
AB  - A 34-year-old man with paroxysmal nocturnal hemoglobinuria (PNH) was scheduled
      for emergency laparotomy. PNH is an acquired disorder of stem cells, and the
      common manifestations are complement mediated hemolytic anemia and deep venous
      thrombosis. Perioperative hemolysis occurs under the activation of complement
      induced by stress such as acidosis, infection, and insufficient pain control.
      Activation of complement secondary leads to platelet aggregation and
      hypercoagulability. We administrated remifentanil for the pain control during the
      operation and fentanyl after the operation. We avoided hypoventilation and
      dehydration to prevent acidosis. Washed red blood cells were given to reduce the
      chance of complement activation and we administrated low molecular weight heparin
      up to the seventh postoperative day to prevent deep venous thrombosis. The
      perioperative course was uneventful without complication.

PMID- 22860312
TI  - [Interference with pulse oxymetry by surgical navigation system, StealthStation
      TRIA].

PMID- 22860313
TI  - [Experience of DMAT rescue activity by doctor-helicopter in Tohoku Area after the
      earthquake].
AB  - We operated rescue activities in Tohoku area after the earthquake of March 11th,
      2011. From our hospital, a doctor-helicopter flew to the staging care unit at
      Hanamaki airport with two members of the disaster medical assistance team (DMAT),
      one of whom was an anesthesiologist. The helicopter carried ten patients by nine
      flight missions, who were the victims of tsunami after the earthquake. There were
      seven doctor-helicopters from all over Japan and did the missions based at
      Hanamaki airport. The missions was quite different from our usual job as an
      anesthesiologist, but we could transfer the patients safely by using some
      knowledge of stabilizing the unstable patients as flight doctors. We report the
      details of our activities by our doctor-helicopters in Tohoku area.

PMID- 22860314
TI  - Tar heel footprints in health care. Rob Doherty.

PMID- 22860315
TI  - Reasons for tanning bed use: a survey of community college students in North
      Carolina.
AB  - BACKGROUND: Tanning bed use is classified as carcinogenic and is associated with
      an increased risk of skin cancer. The aim of this cross-sectional survey was to
      identify the most commonly stated reasons for tanning bed use among a sample of
      male and female community college students in eastern North Carolina. METHODS: A
      brief, self-administered survey was distributed to students during English, Art,
      or Psychology class periods in 5 eastern North Carolina community colleges during
      the 2010 fall semester. RESULTS: The 95% response rate consisted of 487 returned
      surveys. Of the 487 respondents, 12.7% (N = 62) were current users, 24.5% (N =
      119) were past users, and 62.2% (N = 303) reported never using tanning beds.
      Women (79%) were more likely than men (18%) to be current or former tanning bed
      users. Three African Americans reported current tanning bed use (4.8%). Reasons
      for tanning bed use were similar among men and women, with "I think I look better
      when I am tan" being the most commonly cited reason (70.2%) for tanning bed use.
      LIMITATIONS: A convenience sample limits generalizability to all North Carolina
      students attending community college. CONCLUSIONS: Current tanning bed use was
      not widely reported. However, educational strategies for preventing tanning bed
      initiation or recurrence among male and female community college students should
      include appearance-driven factors.

PMID- 22860317
TI  - Policy forum oral health. Introduction.

PMID- 22860316
TI  - Two controlled trials to determine the effectiveness of a mailed intervention to
      increase colon cancer screening.
AB  - OBJECTIVE: Colorectal cancer (CRC) screening is underutilized. Effective and
      efficient interventions are needed to increase its utilization in primary care.
      METHODS: We used UNC Internal Medicine electronic medical records to perform 2
      effectiveness trials. Eligible patients had no documentation of recent CRC
      screening and were aged 50-75 years. The mailed intervention contained a letter
      documenting the need for screening signed by the attending physician in wave A
      and the practice director in wave B, a postcard to request a decision aid about
      CRC screening options, and information about how to obtain screening. RESULT:
      Three-hundred and forty patients of attending physicians in wave A, 944 patients
      of resident physicians in wave B, and 214 patients of attending physicians in
      wave B were included. The intervention increased screening compared with controls
      for attending physicians' patients in wave A (13.1% vs. 4.1%, 95% CI, 3.1%-14.9%)
      but not for resident physicians' patients in wave B (1.3% vs. 1.9%, 95% CI, -2.2%
      to 1.0%). A small increase in screening with the intervention was seen in
      attending physicians' patients in wave B (6.9% vs. 2.4%, 95% CI, -1.4% to 10.5%).
      Requests for decision aids were uncommon in both waves (12.5% wave A and 7.8%
      wave B). LIMITATIONS: The group assignments were not individually randomized, and
      covariate information to explain the differences in effect was limited.
      CONCLUSIONS: The intervention increased CRC screening in attending physicians'
      patients who received a letter from their physicians, but not resident
      physicians' patients who received a letter signed by the practice director.

PMID- 22860318
TI  - Oral health in North Carolina: innovations, opportunities, and challenges.
AB  - Dental disease can have negative and lasting effects on overall health and
      quality of life. The Institute of Medicine of the National Academy of Sciences
      reported last year that close to 5 million children in the United States did not
      receive needed care in 2008 because of costs. Increasing use of dental care has
      been selected by the U.S. Department of Health and Human Services as one of a
      small number of national leading health indicators, designating it as a national
      priority. Innovative initiatives have been undertaken in North Carolina to
      promote oral health, and there have been improvements in the state. For example,
      both the use of dental services among children and their oral health status are
      improving. Yet persistent and difficult challenges remain, such as ensuring an
      adequate workforce for the future, improving oral health literacy, maintaining
      existing programs, and resolving disparities in oral health and lifetime access
      to preventive and treatment services for all North Carolinians. This issue brief
      reviews some oral health initiatives and their outcomes--with a focus on youth.
      Commentaries in the policy forum also focus on access to oral health care;
      assessing, educating, and building the dental workforce; new practice models and
      trends; insurance innovation; and patients with special needs.

PMID- 22860319
TI  - The East Carolina University School of Dental Medicine's approach to dental
      workforce education and reaching underserved areas.
AB  - Access to preventive and oral health care services in many areas of our state
      remains problematic. This paper discusses oral health needs of North Carolinians
      and how a new model of dental education at East Carolina University addresses
      these issues by providing care where it is most needed.

PMID- 22860320
TI  - We're not keeping up with the Joneses: North Carolina has fewer dentists per
      capita than neighboring (and most other) states.
AB  - This commentary provides a data-driven analysis that shows that North Carolina
      faces a geographically maldistributed dentist workforce that is inadequate in
      supply. Not only has North Carolina consistently lagged behind other states in
      dentists per capita for over 10 years, but projections of future workforce supply
      do not show improvement.

PMID- 22860321
TI  - Access to dental health care for children in North Carolina.
AB  - A significant number of children experience dental caries and have low dental
      care utilization rates. This article examines trends in oral health care access
      in the nation, as well as potential barriers, and finally, methods to increase
      access in North Carolina.

PMID- 22860322
TI  - New practice models and trends in the practice of oral health.
AB  - Various internal and external factors are beginning to influence the delivery of
      dental care in North Carolina. This article reviews some of the current trends
      that have led to a shift toward new practice models-some of which are in stark
      contrast to solo private practice.

PMID- 22860323
TI  - Medicaid coverage for adults in North Carolina: what would a reduction in funding
      mean?
AB  - States can achieve short-term cost savings through a reduction in Medicaid adult
      dental benefits. This article presents an overview of the long-term consequences
      of a population of disadvantaged adults faced with a greater oral disease burden
      and the effect of poorer oral health on systemic health and quality of life.

PMID- 22860324
TI  - Policy and proposals that will help improve access to oral care services for
      individuals with special health care needs.
AB  - Historically, access to oral care for individuals with disabilities has been a
      challenge. This commentary provides an overview of this issue and discusses a
      recent policy and several proposals that will help improve outcomes and access to
      oral care for individuals who require special care dentistry services.

PMID- 22860325
TI  - Opportunities in preventive oral health care for children in North Carolina.
AB  - Tooth decay affects more children than any other chronic infectious disease, yet
      it is almost entirely preventable. The Oral Health Section of the North Carolina
      Division of Public Health stresses the importance of prevention and promotes
      opportunities for citizens to achieve good oral health as part of total health.

PMID- 22860326
TI  - Innovations in oral health insurance.
AB  - Dental disease can impact a person's ability to eat and speak, and increases
      absenteeism at work and school. Dental insurance plays an important role in the
      oral health care of North Carolinians as children and adults with dental
      insurance are more likely to get routine dental care, which can prevent dental
      disease.

PMID- 22860327
TI  - Spotlight on the safety net: Cabarrus Health Alliance.

PMID- 22860328
TI  - Running the numbers: Utilization of dental health care services among pregnant
      women in North Carolina.

PMID- 22860329
TI  - Philanthropy profile: Strengthening the oral health safety net: increasing access
      and improving financial sustainability.

PMID- 22860330
TI  - Encouraging collaboration between physicians and advanced practice registered
      nurses in North Carolina.

PMID- 22860331
TI  - Physicians and advanced practice registered nurses: working together as a team.

PMID- 22860332
TI  - Facing down diabetes: are we putting our best foot forward?

PMID- 22860333
TI  - The degrading effect of downgrading staff.

PMID- 22860334
TI  - Unions step up lobbying against moves to introduce regional pay.

PMID- 22860335
TI  - Surplus 'necessary' despite nurses' pay freeze.

PMID- 22860336
TI  - Doctors' pension demands will be paid for by nurses, warns Lansley.

PMID- 22860337
TI  - NMC urged to postpone closure of its professional advisory service.

PMID- 22860338
TI  - Polyclinic opens in Olympic park as volunteer nurses get set for games.

PMID- 22860339
TI  - Unions gather evidence ahead of terms and conditions showdown.

PMID- 22860340
TI  - Nurse leaders speak up for the profession in Downing Street.

PMID- 22860341
TI  - A strong lead.
AB  - Effective clinical leadership protects patients from 'care less care' and aloof
      management. Good leaders lead by example, consistently getting right the small
      things that matter to patients. Leadership programmes give staff the skills to
      harness talent and solve problems.

PMID- 22860342
TI  - Soothing the senses.
AB  - The Namaste programme is a systematic method of treating people with advanced
      dementia. It uses sensory approaches - such as massage and aromatherapy - to
      reach people who are often overlooked at the end of their lives. Here, nurses in
      south London care homes explain how it has brought comfort and pleasure to
      the'silent residents' and made nursing more purposeful and rewarding.

PMID- 22860343
TI  - Giving the gift of life.
AB  - Living donation is the'Rolls-Royce' option for kidney patients, with few risks
      for donors. However, donating lung and liver tissue carries greater risks. Here,
      nurses involved in organ transplants consider the practical and ethical issues of
      the growing practice of living donation.

PMID- 22860344
TI  - Assessing registered nurses' clinical skills in orthopaedics.
AB  - The aim of this article is to explore the views of registered nurses undertaking
      the new Objective Structured Clinical Examination (OSCE), incorporating an
      integrated preparatory skills workshop. The workshop and the OSCE were audited
      with particular regard to the student experience. This article describes the
      audit process and the results of three questionnaires: one carried out before the
      OSCE assessment, a second immediately after the workshop and a third four days
      after the assessment. The results provide an insight into the student experience.

PMID- 22860345
TI  - Eating disorders in people with type I diabetes.
AB  - Individuals with type 1diabetes are at increased risk of developing an eating
      disorder, the effects of which can be physically and psychologically damaging.
      Early detection of an eating disorder and appropriate treatment is therefore
      essential. This article explores the possible factors that may increase the risk
      of people with type 1 diabetes developing an eating disorder, and highlights the
      signs and symptoms to help healthcare professionals detect people at risk so they
      can encourage them to accept appropriate help.

PMID- 22860347
TI  - Skill analysis.

PMID- 22860346
TI  - Emergency care of children and adults with head injury.
AB  - Head injury is common and accounts for a significant proportion of patient
      attendances at emergency departments and minor injury units. While most injuries
      will not be serious in nature, some will be severe. Therefore assessment,
      investigation and early management of head injury are essential to reduce the
      potential risk of disability or even death. This article focuses on emergency
      care of children and adults with head injuries. Advice about the signs and
      symptoms of severe head injury, the importance of computed tomography and after
      care following head injury are outlined.

PMID- 22860348
TI  - Back to business.

PMID- 22860349
TI  - A closer look at how we feel.

PMID- 22860350
TI  - Source of confidence.

PMID- 22860351
TI  - Do parents have to suffer in silence?

PMID- 22860352
TI  - Revising care to meet maternal needs post birth: an overview of the hospital to
      home postnatal study.
AB  - There have been limited improvements in care and support for women post-birth
      despite publication of National Institute of Health and Clinical Excellence
      (NICE) guidelines for routine postnatal care (NICE 2006). NICE recommendations
      included that care should be individualised to women's physical and psychological
      health needs, the content of care should be relevant to the time of recovery post
      birth and information should be offered regarding life-threatening conditions and
      more commonly experienced morbidity. A study was conducted in one maternity unit
      informed by a quality improvement approach to implement NICE guidance. Revisions
      were introduced to hospital systems and processes relevant to the continuum of
      pregnancy, birth and beyond to improve individualised care and women's views of
      this.

PMID- 22860353
TI  - Prolonged jaundice in neonates.
AB  - Jaundice is common in neonates and is often the reason for a parent to consult a
      community midwife or health visitor. It is known that up to 40 per cent of
      breastfed infants are jaundiced at 14 days of age and a proportion of these
      infants are referred to paediatric services for assessment and blood
      investigations. Most often the investigations reveal a high bilirubin level but
      otherwise normal liver function results, leading to a diagnosis of breastfeeding
      jaundice, with no treatment required other than reassurance to the parents and
      monitoring. A recent clinical audit is presented which evaluates current clinical
      practice and the results reflect breast feeding as the main reason for prolonged
      jaundice. This is followed by some guidance for the community health
      practitioners with the aim of reducing referral of otherwise well neonates with
      jaundice and reducing invasive investigations.

PMID- 22860354
TI  - Postpartum urinary symptoms.
AB  - There are clear contributing factors during the antenatal and intrapartum period
      which increase the likelihood of women experiencing postpartum bladder
      dysfunction. Whilst, anecdotally, stress incontinence is often talked about and
      accepted by many women to be part of the post childbirth experience, postpartum
      bladder retention is not. Understanding both the risk factors and the potential
      short- and long term impact of bladder dysfunction are important elements in
      postnatal care. This understanding should guide appropriate management and early
      detection in the postnatal period, considered vital in avoiding long term
      sequelae.

PMID- 22860355
TI  - The coroner's inquest.
AB  - In the awful circumstances of the death of a mother or baby around childbirth,
      midwives need to be prepared for what happens afterwards. This article sets out
      some top tips for midwives appearing at a coroner's court with practical advice
      from Peter Straker, Coroner for West Yorkshire (Western District). You should be
      respectful, say how very sorry you are for the death, dress well, make sure you
      read your notes before the hearing and of course be open, honest and truthful.
      You must also be prepared to answer questions from the family of the deceased as
      well as from the Coroner.

PMID- 22860356
TI  - Enhancing postnatal perineal care.
AB  - Maternal physical and psychological wellbeing during the postnatal period can be
      significantly impaired by perineal trauma sustained during childbirth. Current
      literature emphasises preventative measures, yet there is a lack of a systematic,
      evidence based approach to postnatal perineal care. This is concerning as the
      eighth 'Saving mothers' lives' report (CMACE 2011) identifies genital tract
      sepsis for the first time as the leading cause of maternal deaths. The aim of
      this article is therefore to develop a systematic approach to improve postnatal
      perineal care with a focus on assessment and treatment of perineal pain as well
      as recovery of pelvic floor function.

PMID- 22860357
TI  - Reducing postnatal morbidity.
AB  - There is evidence from large observational studies that women experience a range
      of physical and psychological health problems after birth, many of which do not
      resolve within the postnatal period. The current content, duration and
      definitions of postnatal care are not appropriate to meet the increasingly
      complex health and social needs of women giving birth in the UK today. Despite
      evidence of how the revisions to the content and timing of care could improve the
      clinical and cost effectiveness of universal NHS postnatal services, and positive
      policy support for evidence based care, there is evidence that postnatal
      standards are declining.

PMID- 22860358
TI  - Preparation for birth and beyond: giving birth and meeting our baby.
AB  - A key part of the transition to parenthood is giving birth and mothers and
      fathers need to be carefully prepared for this life changing experience. The time
      generally available for parent education means that it may not be possible or
      desirable to give detailed information about anatomy and physiology and the
      management of labour. Instead, the focus in PBB is on helping group members
      understand what the experience of labour might be like and on helping them
      maximise their personal resources for coping. Additional information is given in
      response to individual or group need and parents are signposted to further
      resources.

PMID- 22860359
TI  - Maternity care of a woman with spina bifida.
AB  - With the increased advancements of corrective surgery for babies with spina
      bifida, more women these days affected by spina bifida are reaching child bearing
      age and having children of their own. This poses both obstetric an medical
      challenges to ensure the safe care of both the mother and child. This case study
      explores the healthcare needs of the woman with spina bifida and the medical and
      obstetric challenges that are posed, particularly in the antenatal period. It
      examines the role of the midwife in providing holistic co-ordinated care to
      ensure that the outcome is both positive and empowering.

PMID- 22860360
TI  - Postpartum anaemia. Are we vigilant enough?
AB  - Anaemia in the immediate postnatal period can manifest itself physically in a
      number of ways. Amongst these are pallor, tiredness, dizziness, loss of appetite
      and oedema (Bewley 2004), all of which could be mistaken for commonly observed
      benign symptoms of the immediate postnatal period. However, left untreated,
      anaemia can severely impact on both the physical and emotional wellbeing of a
      woman and dramatically slow down her recovery (Bewley 2004). This altered state
      of health can also have a detrimental effect on a woman's ability to bond with
      her new child (Abbott et al 1997) and has been identified as a contributory
      factor in the initiation of postnatal depression (Corwin et al 2003). It is
      therefore imperative that, as midwives and student midwives, we take every
      opportunity to closely monitor the wellbeing of women in our care in order to
      facilitate their return to a normal haemoglobin level, promote infant bonding and
      reduce the risk of postnatal depression.

PMID- 22860361
TI  - Kurth E, Powell Kennedy H, Spichiger E et al (2011). 'Crying babies, tired
      mothers: what do we know? A systematic review'. Midwifery, 27(2): 187-194.

PMID- 22860362
TI  - Sleeping like a baby.

PMID- 22860363
TI  - The end of the beginning.

PMID- 22860364
TI  - Let's work together and embrace the change that's best for our patients.

PMID- 22860365
TI  - Scope of practice issues dominate a busy legislative session.

PMID- 22860366
TI  - AMA litigation center challenges FTC encroachment on state licensing.

PMID- 22860367
TI  - "Pay system overhaul will damage nursing".

PMID- 22860368
TI  - AfC plans set out as cartel stalls talks.

PMID- 22860369
TI  - "The hike in NMC registration fees is one financial hit too many".

PMID- 22860370
TI  - "Without time to think, the fire of innovation dies out".

PMID- 22860371
TI  - Reducing the risk surgical site infection.
AB  - Despite being largely preventable, surgical site infections continue to represent
      about a fifth of all healthcare-associated infections. This article examines the
      issues of detection and surveillance, and discusses the key interventions that
      can help to reduce the risk of these infections.ur

PMID- 22860372
TI  - Managing C difficile relapses in the community.
AB  - Nurses face several challenges in caring for patients with recurrent episodes of
      C difficile in the community. This article reports on the development of a
      clinical pathway to meet the needs of older patients and their families.

PMID- 22860373
TI  - Diagnosing and managing lower limb cellulitis.
AB  - The diagnosis of lower limb cellulitis requires careful and structured
      assessment. This article looks at the assessment, diagnosis and management of
      cellulitis, focusing on the lower limb. Assessment should include good skin
      examination as active skin disease, such as venous stasis eczema and athlete's
      foot (tinea pedis), is often overlooked as a primary cause of lower limb
      cellulitis and recurrent episodes.

PMID- 22860374
TI  - Antenatal screening: an on line learning tool.
AB  - The U.K. National Screening Committee has introduced a new "one-stop" online
      resource to update NHS staff quickly and effectively on all six NHS antenatal and
      newborn screening programmes. This article describes how the module was developed
      and its benefits for staff.

PMID- 22860375
TI  - Work in a different world.

PMID- 22860377
TI  - Wisdom in palliative care?

PMID- 22860376
TI  - Lift staff members to make a winning team.

PMID- 22860378
TI  - Family care of the dying in the Republic of Moldova: a qualitative study.
AB  - This paper reports the principle findings of a national, cross-sectional,
      interview-based study of the experiences of people who cared for a dying family
      member in the Republic of Moldova. Study data, collected from 102 interviews,
      covered four broad areas: the experiences of the dying person; family members'
      own experiences of caring; the practice (or non-practice) of any traditional
      customs for dying or death; and family carers' views of their own needs in these
      circumstances. Most carers reported high levels of psychological distress. Dying
      persons were reported to experience significant and unrelieved suffering. The
      practice of traditional customs was uneven, and there were significant levels of
      non-practice. Most respondents expressed a need for greater professional support,
      respite, specialized equipment and medicines, and home help from health care
      professionals. The implications of these findings are discussed in terms of
      potential local developments and international aid.

PMID- 22860379
TI  - Evaluation of a training program to assist care staff to better recognize and
      manage depression among palliative care patients and their families.
AB  - This study was designed to evaluate the effectiveness of a training program to
      improve the knowledge, attitudes, and self-efficacy of palliative care staff and
      thus enable them to better detect and manage depression among palliative care
      patients and their families. Participants were 90 professional carers who
      completed a four-session training program. Knowledge, attitudes, self-efficacy,
      and barriers to working with depressed patients were assessed preintervention,
      post-intervention, and at a three-month follow-up. The results demonstrated that
      compared to the control group, the intervention group had improved in all of
      these areas. Improvements were maintained at the three-month follow-up in all
      areas except attitudes. The results of this study indicate the importance of
      training in managing depression among palliative care staff. Booster sessions
      will likely be needed to ensure that training program gains are maintained.

PMID- 22860380
TI  - What is symptom burden: a qualitative exploration of patient definitions.
AB  - Current definitions of "symptom burden" are largely derived from clinicians, and
      there are many variations in the way the term is used, defined, and
      operationalized. The aim of this study was to explore patient perceptions of
      symptom burden in the context of advanced and incurable disease. A group of 58
      cancer patients followed by a palliative care team answered a single open-ended
      question: "Please define 'symptom burden'". Three authors independently coded and
      analyzed patient responses using a grounded theory approach. They identified six
      themes, the most frequently coded of which were: "can't do usual activities",
      "psychological suffering" and "specific severe symptoms". Our findings indicate
      that the concept of symptom burden is complex and extends beyond numerical
      symptom-scoring systems. In addition to inquiring about specific symptoms, it may
      be important to directly ask patients about their overall burden or experience of
      symptoms.

PMID- 22860381
TI  - Inequalities in end-of-life care for colorectal cancer patients in Nova Scotia,
      Canada.
AB  - Access to high-quality end-of-life (EOL) care is critical for all those with
      incurable cancer. The objective of this study was to examine inequalities in
      access to, and quality of, EOL care by assessing registration in a palliative
      care program, emergency room visits in the last 30 days of life, and location of
      death among individuals who died of colorectal cancer in Nova Scotia, Canada,
      between 2001 and 2008. We used population-based linked administrative data and
      performed multivariate logistic regression models to assess the association
      between socio-economic, geographic, and demographic factors and outcomes related
      to access to, and quality of, EOL care (n=1201). This study demonstrates that
      although access to, and quality of, EOL care appears to have improved, there
      remain significant inequalities throughout the population. Of primary concern is
      the variation in access to, and quality of, EOL care based on geographic location
      of residence and patient age.

PMID- 22860382
TI  - Negotiating relational practice patterns in palliative home care.
AB  - Providing palliative care in the home presents a variety of challenges for nurses
      and other care providers. As part of a focused ethnographic study examining
      client/caregiver/care-provider relationships within the socio-cultural context of
      home-based palliative care, this paper describes the provision of palliative care
      to Canadian seniors with advanced cancer from the perspective of nurses. Data
      were collected through in-depth interviews (n=19) with three palliative care
      nurses and participant observations in four households over a six-to-eight-month
      period. Home-based palliative care nursing was depicted in this study as a
      dialectical experience, revealing three relational practice patterns: making time
      forfeiting time, connecting-withdrawing, and enabling-disabling. Nurses attempted
      to negotiate the tensions between these opposing approaches to palliative care.
      Study findings suggest that the sociocultural context of palliative care is not
      conducive to high-quality palliative care and provide several insights related to
      future directions for practice, policy, and research.

PMID- 22860383
TI  - Palliative and end-of-life care in Newfoundland's deaf community.
AB  - The deaf community is a distinct cultural and linguistic community (the uppercase
      D is a cultural identification). Compared to the general population, the deaf
      community, as a social group, experiences poorer health status. Deaf people seek
      care less frequently than the general population and have fewer interactions with
      the health system. Their encounters with the health system are often
      characterized by communication difficulties, fear, mistrust, and frustration.
      Qualitative research was used to explore the experiences of family caregivers who
      provided end-of-life care for a deaf person. Key findings indicate that the deaf
      community has limited understanding of their options for palliative and end-of
      life care. Communication and health literacy are key barriers to accessing
      appropriate end-of-life care. Pain and symptom management, consideration of
      physical environments, and limited access to bereavement care are common issues
      faced by deaf people when caring for loved ones at the end of life.

PMID- 22860384
TI  - On prevalence disparities in recent empirical studies of deathbed visions.

PMID- 22860385
TI  - John Keats and Wilfred Owen--mortality, mystery, and the pursuit of truth:
      lessons for palliative care.

PMID- 22860386
TI  - Anna: an end-of-life narrative.

PMID- 22860387
TI  - Symptom management using methotrimeprazine: expanding the definition of respite
      sedation.

PMID- 22860388
TI  - Re: When newborn babies have to die...perinatal palliative care?

PMID- 22860389
TI  - Mentoring as an essential component of our commitment to SUNA.

PMID- 22860390
TI  - Vaginal support pessaries: indications for use and fitting strategies.
AB  - Flexible silicone vaginal support pessaries offer a low-risk, effective option
      for treatment of symptoms of pelvic organ prolapse. This first article in a three
      part series summarizes clinical recommendations and current evidence related to
      pessary indications, choice, and fitting.

PMID- 22860391
TI  - Pessary care: follow up and management of complications.
AB  - Successful use of vaginal support pessaries requires provider and patient
      understanding of expected symptom-relief, potential complications, self-care
      options, and evaluation and treatment of pessary-related problems. This second
      article in a three-part series summarizes clinical recommendations and evidence
      related to pessary management.

PMID- 22860392
TI  - Managing a pessary business.
AB  - In this final article in a series of three, components of pessary fitting,
      provision, and follow up are reviewed from a business perspective related to
      supplies, patient flow, billing, and coding.

PMID- 22860394
TI  - Traces: making sense of urodynamics testing--Part 11: quantitative analysis of
      micturition via the voiding pressure flow study: pressure-flow nomograms.
AB  - The voiding pressure flow study is the gold standard for evaluating micturition.
      Part 10 of the Traces series described techniques for evaluating micturition via
      the voiding pressure flow study; it focused on interpretation of results
      qualitatively via inspection and classification of flow pattern, detrusor
      contraction amplitude and duration, pelvic floor muscle response to voiding, and
      urethral resistance. This article discusses quantitative analysis of the voiding
      pressure flow study using nomograms that measure the magnitude of urethral
      resistance (bladder outflow obstruction) and/or detrusor contraction strength.

PMID- 22860393
TI  - Complementary and alternative therapies for urinary symptoms: use in a diverse
      population sample qualitative study.
AB  - Study participants reported a range of remedies used to treat urinary symptoms,
      from popular products, such as saw palmetto, to less commonly known remedies,
      such as moabi. Participants learned about remedies through social network rather
      than from their primary care provider.

PMID- 22860395
TI  - Health literacy.

PMID- 22860396
TI  - Facilitating the transformation of information technology: strategies for nurse
      administrators.
AB  - The effects of technology on the healthcare system have been multifaceted. While
      the benefits clearly outweigh the negatives that come with technology, there are
      various challenges that arise with technological implementation. The nurse
      administrator's role is to ensure that technological systems are transformed
      effectively and that financial, ethical, and legal implications are considered.

PMID- 22860397
TI  - [Nitric oxide as the regulator of intracellular homeostasis in the uterus
      myocytes].
AB  - The published data on the mechanisms and regulation of active and passive Ca2+
      transport in the myometrium have been analyzed. Particular attention is paid to
      the cGMP-dependent and independent pathways of action of nitric oxide or its
      derivatives on intracellular Ca2+ homeostasis of uterine smooth muscle and its
      contractile activity. Information on the effect of nitric oxide on Ca2+ 
      transport systems of other types of smooth muscles is provided in a comparative
      aspect. Based on own experimental results and literature data a scheme of NO
      action in the myometrium is suggested in which nitric oxide or its derivatives
      cause Ca2+ -dependent polarization of the sarcolemma. In accordance with our
      results, this effect may be based on the increase of sarcolemma Ca2+ permeability
      under the influence of NO or its derivatives and the stimulation of at least the
      initial passive transport of the cation in the myocytes mediated by
      dihydropyridine-sensitive channels. Additional factors that contribute to the
      polarization of the membrane are the increase of protons transport from the
      muscle cells and stimulation of Na+, K+ -ATPase. Acting on the sarcoplasmic
      reticulum, nitrosactive compounds activate the inclusion of calcium in this
      compartment and inhibit Ca2+ -induced release of the cation. The latter effects
      are able to provide compensation for NO-induced Ca2+ increase in myocytes and
      supress the electromechanical coupling at Ca2+ release from the reticulum. NO
      derivates also inhibit a key link in the smooth muscle contractile act--the
      formation of the Ca2+ -calmodulin complex.

PMID- 22860398
TI  - [Avidity and competitive inhibition of binding native and chaotropically modified
      immunoglobulins with protein and glycolipid antigens].
AB  - It is established, that native and chaotropically modified immunoglobulins
      essentially differ by avidity and character of competitive inhibition of binding
      with protein (ovalbumin), glycolipid (lipopolysaccharides) antigens and native
      double-strand DNA. Apparently, it is connected with structural and functional
      distinctions of their antigen-binding centres.

PMID- 22860399
TI  - [Peculiarities of antioxidant defense system organization of the Black Sea
      mollusks Mytilus].
AB  - Antioxidant (AO) system and lipid peroxidation (LP) in tissues of two species of
      the Black Sea bivalve mollusks Mytilus galloprovincialis and Anadara
      inaequivalvis were investigated. The activity of superoxide dismutase (SOD,
      1.15.1.1), catalase (1.11.1.6), glutathione peroxidase (GP, 1.11.1.9),
      glutathione reductase (GR, 1.6.4.2), concentrations of reduced glutathione (GSH)
      and TBA-reactive products were determined in the foot, hepatopancreas and gills
      of mature mollusks. The characteristics of AO complex and LP products connected
      with tissue and species specificity of mollusks were found. Hepatopancreas of
      mussels has been found to have higher values of all characteristics investigated,
      except GP. The gills and the foot of anadara have been found to be involved in AO
      defense along with hepatopancreas: maximum activity of GR, catalase and SOD was
      found in the gills and the highest activity of GP and maximum level of GSH was
      observed in the foot. Anadara has been shown to have higher antioxidant potential
      and lower level of oxidative stress because the LP intensity in all tissues
      examined of the hemoglobin-containing mollusk was twice lower in comparison with
      the mussel.

PMID- 22860400
TI  - [The influence of N-stearoylethanolamine on the activity of antioxidant enzymes
      and on the level of stable NO metabolites in the rat testes and blood plasma at
      the early stages of streptozotocine-induced diabetes].
AB  - The influence of N-stearoylethanolamine was investigated on the activity of
      enzymes of antioxidant protection and content of stable metabolites of nitric
      oxide (NO) in the testes and plasma of rats at the early stages of development of
      streptozotocine-induced diabetes mellitus. It was shown that the activity of
      superoxide dismutase, catalase is reduced in the plasma and testes of animals
      with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A
      significant increase in the amount of nitrite and nitrate anions was revealed in
      the plasma of rats, while only the level of nitrite was significantly changed in
      the testes of animals. The per os administration of the NSE aqueous suspension in
      a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed
      to the normalization of catalase activity in the testis, which correlated with a
      decrease in the amount of TBA-reacting products and activity of superoxide
      dismutase and catalase in the blood plasma of animals; the use of NSE also
      contributed to the reduction of nitrite content in the gonads and to
      normalization of both nitrite and nitrate in the blood plasma of rats. The NSE
      administration to intact animals caused an increase in superoxide dismutase
      activity and significantly reduced the content of stable NO metabolites in the
      blood plasma of animals.

PMID- 22860401
TI  - [Kinetic properties of Na+, K+ activated, Mg2+ -dependent ATP-hydrolysis of blood
      lymphocytes in patients with rheumatoid arthritis and ankylosing
      spondyloarthritis].
AB  - The comparative analysis of the kinetic properties of ouabain-sensitive Na+, K+ 
      ATPase activity of saponin-perforated blood lymphocytes of donors and patients
      with rheumatoid arthritis (RA) and ankylosing spondyloarthritis (AS) was carried
      out. When analyzing the alterations in hydrolase activity of the examined enzyme
      it was shown that in the blood lymphocytes of patients with RA and AS the primary
      active transport of Na+ and K+ ions is less intensive in comparison with
      practically healthy donors, but it is characterized by almost the same capacity
      as in donors. The affinity constant of Na+, K+ -ATPase for ATP in the blood
      lymphocytes in patients with RA and AS is greater 3.1 and 2.5 times,
      respectively, in comparison with healthy donor. It was found that in conditions
      of rheumatic pathology in immunocompetent cells the inhibition of Na+, K+ -ATPase
      activity is not related to the reduction of maximum reaction rate, but is related
      to the decrease of Na+, K+ -ATPase affinity to ATP. However, Mg2+ -binding center
      of Na+, K+ -ATPase in patients with RA and AS remains native. It was identified
      that the affinity constant of Na+, K+ -ATPase to Na+ ions in the blood
      lymphocytes of patients with RA and AS is 2.75 times lower than its value in
      healthy donors. Na+, K+ -ATPase of the blood lymphocytes of patients with RA and
      AS retains its native receptor properties and sensitivity to ouabain does not
      change.

PMID- 22860402
TI  - [The effect of agmatine on L-arginine metabolism in erythrocytes under
      streptozotocin-induced diabetes in rats].
AB  - The effects of agmatine on oxidative and nonoxidative metabolic pathways of L
      arginine were investigated both in plasma and erythrocytes under experimental
      diabetes mellitus. It was indicated, that agmatine prevents the development of
      oxidative-nitrosative stress in diabetic rats. After treatment of animals by
      agmatine NO-synthase methabolic pathway of L-arginine is depressed whereas
      arginase one increases in erythrocytes of rats with experimental diabetes
      mellitus.

PMID- 22860403
TI  - [Changes of the state of rat kidneys under guerin carcinoma development and use
      of cytostatics].
AB  - It was shown that development of the Guerin carcinoma and introduction of
      cisplatin led to the damage of the kidneys of rats that was confirmed by a
      relative increase of weight, proteinuria, change of gamma-glutamyl transpeptidase
      and lactate dehydrogenase activity in the urea and tissue homogenates of the
      kidneys, by a decrease of relative reabsorption and glomerular filtration.
      Introduction of nanoliposomal forms of the rhenium cluster compounds led to
      normalization of above mentioned diagnostic indexes and to reduction of the toxic
      cisplatin influence that was confirmed by biochemical and morphological
      investigations.

PMID- 22860405
TI  - Effect of sodium chloride and nitroprusside on protein carbonyl groups content
      and antioxidant enzyme activity in leaves of corn seedlings Zea mays L.
AB  - The effect of sodium nitroprusside (SNP) and sodium chloride (NaCl) on protein
      carbonyl group content and activity of antioxidant enzymes was investigated in
      leaves of maize seedlings. Incubation with NaCl and SNP+NaCl increased the
      content of carbonyl proteins after 24 h. Treatment with SNP+NaCl during 48 h
      showed lower and after 72 h higher carbonyl protein content than that in the
      control. Catalase activity was higher in the leaves of SNP+NaCl-treated than in
      the leaves of SNP-treated seedlings after 24 h. Ascorbate peroxidase activity
      increased after incubation with 0.2 mM SNP for 24 h. Significant increment of
      guaiacol peroxidase activity was obtained in all treated groups in comparison
      with the control after 72 h. Glutathione-S-transferase activity increased after
      48 h seedling treatment with NaCl or SNP and 72 h seedling incubation with NaCl.
      Under experimental conditions used, glutathione reductase activity was virtually
      not affected. It is proposed that SNP can be used to prevent salt-induced
      oxidative stress in maize.

PMID- 22860404
TI  - [Antioxidant and antitumor activity of dirhenium dicarboxylates in animals with
      guerin carcinoma].
AB  - The antioxidant and anticancer properties of dirhenium dicarboxylates of cis- and
      transconfiguration with different organic ligands in a model of tumor growth
      (Guerin carcinoma) were studied. It was shown that compounds of different
      configuration had similar antitumor effect, and dirhenium (III) cis
      dicarboxylates were characterized by higher antioxidant activity and degree of
      activation of erythrocyte superoxide dismutase (SOD) in comparison with trans
      isomers. The dependence between the structure of dirhenium (III) dicarboxylates
      and their ability to activate erythrocyte SOD in the model of tumor growth was
      shown for the first time. The in vitro studies have shown that rhenium compounds
      of cis- and transconfiguration interacted similarly with erythrocyte SOD,
      changing the protein secondary structure. In contrast to trans-dicarboxylate, for
      cis-dicarboxylate the SOD-like activity was demonstrated to be on the first
      minutes of the xantine-oxidase reaction. The studied features of the interaction
      between rhenium compounds and SOD in vitro explain only partly the activation of
      SOD in experiments in vivo. The attempt is made to explain the differences in the
      mechanisms of antioxidant activity of dirhenium cis- and trans-dicarboxylates.

PMID- 22860406
TI  - [The action of adaptogenic preparations on vacuolar proton pumps activity in corn
      root cells under salt stress conditions].
AB  - The function of two electrogenic H+ -pumps in plant vacuolar membrane (tonoplast)
      and their response to the salt stress conditions and adaptogenic preparations
      have been studied. Experiments were carried out on tonoplast fraction isolated
      from the roots of corn seedlings grown in water culture which were exposed at 7
      day age in the presence of 0.1 M NaCl during 1 or 10 days. The role of every H+ 
      pump in potential generation was elucidated by assaying transport and hydrolytic
      activity of enzymes--V-type H+ -ATPase and H+ pyrophosphatase represented their
      mechanisms. It was found in the control variant that transport activity H+ -PPase
      exceeded considerably H+ -ATPase one in the tonoplast from 7-day seedlings.
      However this situation was changed in 18-day seedlings by H+ -ATPase transport
      activity increasing with age whereas its hydrolytic one was decreased. Both NaCI
      expositions caused the progressive decrease of transport and hydrolytic activity
      of H+ -PPase whereas H+ -ATPase responded to this factor by increasing transport
      activity, while its hydrolytic one fell. Bioactive preparations Methyure and
      Ivine (10(-7) M) used by seed soaking caused a further increase of H+ -ATPse
      transport activity especially in the presence of NaCl whereas H+ -PPase one was
      not changed. Methyure effect in these experiments was more pronounced. Obtained
      results demonstrated participation of tonoplast H+ -pumps in plant adaptation to
      NaCI which can be realized by amplification of Na+ -H(+) antiporter energization.
      An important role of vacuolar H+ -ATPase in growth and adaptation processes in
      plants has been proved.

PMID- 22860407
TI  - [On true and apparent Michaelis constants in enzymology. III. Is it linear
      dependence between apparent michaelis constant and limiting rate and is it
      possible to determine the substrate constant value using this dependence?].
AB  - The Slater-Bonner method which is used for graphic determination of substrate
      constant (Ks) by linear dependence of apparent Michaelis constant (Km(app)) on
      the limiting rate (V(app)) of enzyme-catalysed reactions with activator
      participation has been critically analysed. It has been shown that although it is
      possible to record the mechanisms of such reactions as a scheme similar to
      Michaelis-Menten model which allow to find correlation Km(app) and V(app) as
      equation Km(app) = Ks + V(app)/k1[E]0 ([E]0 is a total enzyme concentration, k1
      is a rate constant of enzyme-substrate complex formation from free enzyme and
      substrate) in order to calculate Ks and individual rate constants (k1, k(-1)),
      but this approach for investigation of all reactions with activator participation
      ought not to be used. The above equation is not obeyed in general, it may be true
      for some mechanisms only or under certain ratios of kinetic parameters of enzyme
      catalysed reactions.

PMID- 22860408
TI  - [Avidity of bivalent antibodies. Problems of its experimental determination and
      theoretical evaluation].
AB  - Some problems of experimental determination or theoretical evaluation of antibody
      avidity are considered. It was shown that in order to determine the fraction of
      nonoccupied antibodies in their mixture with the excess of the corresponding
      antigen which is required to estimate avidity the methods should be used which
      are more sensitive than ELISA. The available methods did not allow determining
      the avidity of bivalent antibodies because of many reasons. However, in the
      recent years new methods were suggested that make it possible to evaluate the
      avidity of bivalent antibodies and that of the receptors which consist of two
      binding sites connected by a flexible linker of the known length. Thus, there are
      all possibilities now for determining the avidity of bivalent antibodies in
      experiments or by theoretical methods.

PMID- 22860409
TI  - [Laureates of the O. V. Palladin Prize of NAS of Ukraine of 1975-1976].

PMID- 22860410
TI  - [Development of the problem of tumor growth biochemistry in the works by
      professor Vasyl Pavlovych Korotkoruchko, doctor of sciences in biology (1956
      1989)].

PMID- 22860411
TI  - [Pathophysiological characteristics of rat pulmonary hypertension and cor
      pulmonale induced by monocrotaline].
AB  - OBJECTIVE: To explore the mechanism of pulmonary hypertension and Cor Pulmonale
      rat models induced by monocrotaline (MCT). METHODS: Twenty Wistar male rats were
      randomly divided into normal control group and model group (n= 10), which
      received a single intraperitoneal injection of MCT solution (50 mg/kg , the first
      day) or dissolvant, respectively. On day 28 after MCT administration, the
      hemodynamic parameters were assessed; levels of tumour necrosis factor-alpha (TNF
      alpha), nitric oxide (NO), endothelin-1 (ET-1), B-type natriuretic peptide(BNP)
      in pulmonary tissue or blood were measured using radio immunoassay or nitrate
      reductase method. RESULTS: 28 days after MCT injection, compared with control
      group, right ventricle systolic pressure (RVSP) increased and heart rate(HR),
      mean arterial pressure (MAP) decreased; Levels of TNF-alpha, NO, ET-1 in
      pulmonary tissue or blood increased significantly in MCT group. CONCLUSION: The
      potential mechanism of MCI- induced pulmonary hypertension and Cor Pulmonale rat
      models associates with increasing TNF-alpha, NO, ET-1 levels in vivo, which
      results from inflammatory injury of lung tissue and blood vessels induced by MCT.

PMID- 22860412
TI  - [Influence of tea polyphenols on the free radical metabolism in the liver cells
      of nutritional obesity rats].

PMID- 22860413
TI  - [Protective effect of intermittent hypobaric hypoxia on cardiomyocytes injury
      induced by hydrogen peroxide].
AB  - OBJECTIVE: To observe the protective effect and mechanism of intermittent
      hypobaric hypoxia (IHH) on cardiomyocytes induced by hydrogen dioxide. METHODS:
      Male guinea pigs were divided randomly into two groups (n = 10): intermittent
      hypoxia group (IHH), and control group (non-IHH). The IHH guinea pigs were
      exposed to a simulated 5,000 m high altitude and hypoxia in hypobaric chamber for
      28 d, 6 h/d. The control guinea pigs were kept in the same environment as IHH
      except hypoxia exposure. Cardiomyocytes were enzymatically isolated from left
      ventricle of non-CIHH or CIHH guinea pigs. The contractile was assessed in guinea
      pigs by a video-based motion edge-detection system. The contents and activities
      of malondialdehyde(MDA), lactate hydrogenase(LDH) and antioxidant enzymes were
      evaluated by using biochemical methods. RESULTS: 1. Hydrogen peroxide could
      induce contractile and diastole dysfunction, the latent period was longer in IHH
      cardiac myocytes. 2. After hydrogen peroxide(300 micromol/L, 10 min) perfusion,
      LDH and MDA contents in supernatant increased significantly in non-IHH and CIHH
      cardiomyocytes (P < 0.01), Whereas the contents of MDA and LDH in IHH
      cardiomyocytes were lower than those in non-IHH cardiomyocytes (P < 0.01). 3. The
      activities of superoxide dismutase (SOD) and catalase (CAT) were significantly
      increased in the myocardium of IHH guinea pigs, after hydrogen peroxide (300
      micromol/L, 10 min) perfusion, SOD and CAT activities decreased significantly in
      non-IHH and CIHH cardiomyocytes (P < 0.01), whereas the activities of SOD and CAT
      in CIHH cardiomyocytes were still higher than those in non-IHH cardiomyocytes.
      CONCLUSION: IHH had a protective effect on cardiomyocytes injury induced by
      hydrogen peroxide, which might relate with its antioxidation effects.

PMID- 22860414
TI  - [Influence of angiotensin II on heart rate variability in rabbits].

PMID- 22860415
TI  - [Effects of simulated weightlessness on emotional behaviour in rats].
AB  - OBJECTIVE: To study the influence of 14- day simulated weightlessness on
      emotional behaviour in rats. METHODS: Sixteen from twenty male SD rats were
      selected and assigned to a 2-group design: the control group and the tail
      suspension (TS) group (n = 8). The essay deployed typical methods for assessing
      emotional activity in the current, including food-intake and body weight
      variation, open field testing, sucrose preference testing and the evaluation of
      emotional arousal level to test emotional behavior. RESULTS: 1. After 14- day
      simulated weightlessness for rats, their food-intake and body weight increase
      were less than those in the control group. 2. The ability of movement reduced in
      rats, the number of locomotion was significantly lower than that in the control
      group (P < 0.05) and the frequency of self-grooming was significantly higher than
      that in the control group(P <0.01. 3. A higher level of emotionality in TS group
      was recorded. 4. Sucrose preference was not observed in TS group. CONCLUSION: It
      demonstrated depression, anxiety and nervous symptom occurred in the TS rats with
      a certain degree of nervous reaction but no anhedonia.

PMID- 22860416
TI  - [Study on toxicity and harm of acute exposure to lead on nervous system in mice].

PMID- 22860417
TI  - [Effect of serotonin depletion on seizures learning-memory in pilocarpine-induced
      epileptic rats].
AB  - OBJECTIVE: To investigate the relationship between serotonin (5-HT) and epilepsy
      and the mechanism of learning-memory in pilocarpine (PILO)-induced epileptic rats
      after 5,7-dihydroxytryptamine (5,7-DHT) microinjection in median raphe nucleus.
      METHODS: Adult S D rats were randomly divided into 3 groups: PILO group, PILO+
      5,7-DHT group, vehicle control group; PILO group was divided into two groups by
      status epilepticus (SE): PILO + SE group and PILO - SE group. The rats' seizures
      and cortex electroencephalography (EEG) were observed by video EEG. The rats'
      spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic
      neuron in raphe nuclei was observed by immunohistochemistry. RESULTS: After
      treatment of 5,7-DHT (PILO + 5,7-DHT group), the success rate, the mortality and
      the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy
      model were all improved. Compared with the control group, the number of
      serotonergic neuron in raphe nuclei was decrease in PILO + SE group (P < 0.05).
      Moreover, it's extremely decrease in PILO + 5,7-DHT group (P < 0.01). Compared
      with control group, the mean escape latency was prolonged, the times of crossing
      target was decreased and the retention time in target zone was shortened in PILO
      + SE group (P < 0.05), but there was no significant difference between PILO + SE
      group and PILO + 5,7-DHT group. CONCLUSION: Depletion of serotonin may facility
      the rats' epileptic seizures, but we could not interpret which may cause
      epileptic rats' cognitive deficit.

PMID- 22860418
TI  - [Application of recording SK2 current in human atrial myocytes by perforated
      patch clamp techniques with the mix of beta-escin and amphotericin B].
AB  - OBJECTIVE: To establish a perforated patch-clamp technology with amphotericin B
      and beta-escin and to research the regulation of small conductance calcium
      activated potassium channel SK2 currents by calcium ions. METHODS: Single human
      atrial myocytes were enzymatically isolated from the right atrial appendage.
      Amphotericin B and / or beta-escin were used by perforated electrode liquid. The
      regulation of SK2 current by calcium ions in human atrial myocytes was performed
      with the perforated patch-clamp technique. The intracellular calcium changes were
      measured by the intracellular calcium test system. RESULTS: Mixed perforated
      electrode liquid compared with 150 microg/ml amphotericin B or 6.88 microg/ml
      beta-escin alone, it was easy to seal cells and activate SK2 current by the
      former method. Moreover, the ration of F340/380 was consistent with the change of
      intracellular free calcium ion concentration increase after the formation of
      perforation. The ration of F340/380 was measured by intracellular calcium test
      system. CONCLUSION: The appropriate concentration of amphotericin B mixed with
      beta-escin can form a stable whole-cell patch recording technology that is
      appropriate for the research of SK2 current regulation by intracellular calcium.

PMID- 22860419
TI  - [Relationship of haplotypes of FgBbeta-1420G/A -993C/T, and BsmAIG/C with
      functional expression and cerebral infarction].

PMID- 22860420
TI  - [Breeding of transgenic mice expressing human tau isoform with P301L mutation and
      identification of homozygous transgenic mice].
AB  - OBJECTIVE: To establish homozygous transgenic mouse strain expressing human tau
      isoform with P301L mutation. METHODS: Five transgenic mice expressing human tau
      isoform with P301L mutation were obtained by microinjection into male nuclei.
      Homozygote and hemizygote were identified by PCR and real-time fluorescent
      quantitative PCR. RESULTS: Ninety five homozygous transgenic mice were selected,
      and the results indicated that homozygous transgenic mice were superior to
      hemizygote in simulating the changes of biological characteristics. CONCLUSION:
      Exogenous gene tau is able to stably transmit to next generation and the
      combination of SYBR Green real-time fluorescent quantitative PCR with the
      traditional mating is a fast, reliable and economical way to screen homozygous
      and hemizygous transgenic mice.

PMID- 22860421
TI  - [Correlation analysis of aspirin resistance and cycloxygenase-1 haplotype in old
      Chinese patients with cardio-cerebrovascular diseases].
AB  - OBJECTIVE: To investigate whether cyclooxygenase-1 (COX-1) haplotype is
      associated, with aspirin resistance. METHODS: The participants were 431 old
      Chinese Han patients with cardiovascular and cerebrovascular diseases who took
      aspirin. The 59 patients with aspirin resistance (AR) by light transmittance
      aggregation acted as the cases; the 372 aspirin-sensitive patients were the
      controls. The relationships between AR and 6 single nucleotide polymorphisms
      (SNPs) in COX-1 gene. rs1888943 (8759C/T), rs1330344 (1676A/G), rs3842787 (exon2,
      50C/T, p.Pro17Leu), rs5787 (exon 4, 323G/A, p. ARg108Gln), rs5789 (exon7, 709C/A,
      p. Leu237Met) and rs5794 (exonl0, 1330G/A, p.Va1481Ile) were investigated by the
      USA Sequenom high-throughput single nucleotide polymorphisms (SNP) genotyping
      systems. RESULTS: In this case-control trial, the frequency of mutant CGCGCC
      haplotype in case was 0.48 (57/118) and in control was 0.39 (286/742), which was
      significantly higher than that of the control group (P < or = 0.05). CONCLUSION:
      COX-1 haplotype is associated with aspirin resistance in old Chinese Han patients
      with cardio-cerebrovascular diseases, mutant CGCGCC-haplotype carriers of COX-1
      has a significant significantly increased risk of AR.

PMID- 22860422
TI  - [Effect of notoginsenoside Rg1 on p38MAPK expression of pulmonary arterial smooth
      muscle cells exposed to hypoxia hypercapnia].
AB  - OBJECTIVE: To study the effect of Notoginsenoside Rgl on p38 mitogen activated
      protein kinase (p38MAPK) expression in pulmonary artery smooth muscle cells
      (PASMCs) cultured in hypoxia hypercapnia. METHODS: SD rat PASMCs was primary
      cultured, the cells of passage 2- 5 were divided into six groups: normoxic group
      (N group), hypoxia hypercapnia group (H group), dimethyl sulfoxide (DMSO) control
      group (HD group), Rg1 treated group (Rg low dose, Rg middle dose and Rg high dose
      group). Western blot was used to detect the expression of p-p38MAPK protein, and
      RT-PCR to determine the expression of p38MAPK mRNA. RESULTS: Western blot and RT
      PCR analysis indicated that the expression of p-p38MAPK protein and p-p38MAPK
      mRNA were significantly higher in HD group than those in N group (P < 0.01).
      Whereas, in Rg1 treated groups, the level of p-p38MAPK markedly decreased (P <
      0.01) in dose-dependent manner. CONCLUSION: Notoginsenoside Rg1 has protective
      effects on PASMCs under hypoxia hypercapnia condition, which may be related to
      inhibiting expression of p38MAPK.

PMID- 22860423
TI  - [The expression of hypoxia-inducible factor-1alpha and its hydroxylases in
      pulmonary arteries of patient with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To observe the expression of hypoxia-inducible factor-lalpha subunit
      (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor
      inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive
      pulmonary disease (COPD). METHODS: Pulmonary specimens were obtained from
      patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD
      group) and 14 without COPD (control group). The ratio of vascular wall area to
      total vascular area (WA%) and pulmonary artery media thickness (PAMT) was
      observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and
      protein were detected by in situ hybridization and immunohistochemistry
      respectively. RESULTS: WA% and PAMT of COPD patients(50 microm +/- 9 microm, 40%
      +/- 5%, were statistically different from those of the control subjects (39
      microm +/- 6 microm, 31% +/- 4%, P < 0.01). Relative quantification of mRNA and
      protein levels (absorbance, A) showed that HIF-lalpha mRNA and protein levels in
      COPD group (0.230 +/- 0.036,0.275 +/- 0.039) were statistically higher than those
      of the control subjects (0.174 +/- 0.029, 0.102 +/- 0.015, P < 0.01 ), and that
      the protein level increased more markedly. PHD1 mRNA in COPD subjects (0.180 +/-
      0.030) was comparable to that in control group (0.191 +/- 0.029, P > 0.05); PHD2
      and PHD3 mRNA levels in COPD (0.245 +/- 0.044, 0.252 +/- 0.023) were
      significantly higher than those in control group(0.182 +/- 0.028, 0.127 +/-
      0.017, P < 0.01). On the other hand, in COPD subjects PHD1 protein (0.104 +/-
      0.015) was significantly lower(P < 0.01), whereas PHD2 protein (0.274 +/- 0.044)
      was significantly higher(P < 0.01) than those in control group(0.209 +/- 0.023,
      0.219+/- 0.043). As for PHD3 protein, no significant changes were observed
      between the two groups (0.161+/- 0.023 in COPD, 0.146 +/- 0.021 in control, P >
      0.05). FIH mRNA and protein both showed no differences between the two groups.
      Linear correlation analysis showed that HIF1alpha protein was positively
      correlated with WA%, PAMT, PHD2 mRNA and protein, PHD3 mRNA, and that HIF1alpha
      protein was negatively correlated with PHD1 protein. CONCLUSION: PHDs may be
      involved in the process of hypoxic pulmonary vascular remodeling in COPD via
      regulation of HIF-1alpha gene expression

PMID- 22860424
TI  - [Effects of the compound extract of Chinese medicine on free radical metabolism
      of the rat brain in different states].

PMID- 22860425
TI  - [Protective effects of SUR2B/Kir6.1 potassium channel opener natakalim against
      RAVECs injuries induced by hypoxia].
AB  - OBJECTIVE: To investigate the protective effects of natakalim against rat aortic
      vascular endothelial cells (RAVECs) injuries induced by hypoxia and its
      mechanisms. METHODS: Selecting RAVECs as a cell model injured by hypoxia, these
      RAVECs were divided into 5 groups: i.e. control group, hypoxia group, natakalim
      low, medium and high group. The cell survival rate was determined by MTT assay,
      con was measured using Griess Assay, RT-PCR was used to examine t he expression
      of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor
      (VEGF), endothelin-1 (ET-1) mRNA in RAVEC. RESULTS: Natakalim could reverse
      hypoxia-induced changes in endothelial cell function, including increased
      endothelial cell survival rate and level of NO concentration, significantly
      inhibited the hypoxia-induced endothelial ICAM-1, ET-1, VEGF mRNA expression
      levels increased. CONCLUSION: Natakalim have protective effects on hypoxia
      induced changes in endothelial cell function, increasing of permeation, excess
      expression of cell adhesion molecules.

PMID- 22860426
TI  - [The correlation of age with the risk of multiple organ dysfunction syndrome in
      the elderly patients with congestive heart failure and hypertension].
AB  - OBJECTIVE: To study the prediction value of age and congestive heart failure
      (CHF) for occurrence of multiple organ dysfunction syndrome elderly(MODSE) in old
      patients with hypertension. METHODS: Medical history of 19,996 cases (aged over
      60 year) admitted to PLA General Hospital because of hypertension or developing
      hypertension during hospital stay from Jan 1993 to Dec 2008 were analyzed
      retrospectively. According to age the patients were divided into four groups: 60
      69 year group; 70-79 year group; 80-89 year group; > or = 90 year older group.
      The incidence of CHF and the morbidity of MODSE induced by CHF at different ages
      and different boundary ages were investigated. RESULTS: 1. The incidence of MODSE
      in CHF cases was higher than that in the non-CHF cases (7.43% versus 3.05%,
      Chi(2) 195.15, P < 0.01), showing CHF were the important factor in happening of
      MODSE. 2. The incidence of CHF and the morbidity of MODSE were 10.60% versus
      18.88% versus 30.11% versus 60.57%, P <0.05, P < 0.05 and 1.6 versus 7.0 versus
      17.08 versus 25.47% , in 60-69 year group; 70-79 year group; 80-89 year group; >
      or =90 year older group, P < 0.05. Occurrence of CHF and that of MODSE were
      positively correlated with age (r = 0.696 - 0.987, P < 0.01). High risk
      population of MODSE induced by CHF were old patients with hypertension above 69
      year old. CONCLUSION: The age is valuable for early prediction of MODSE induced
      by CHF in old patients with hypertension. The distinctly boundary age for the
      incidence of MODSE induced by CHF in old patients with hypertension is 69.

PMID- 22860427
TI  - [The different roles of the spinal protein nNOS and iNOS in morphine naloxone
      precipitated withdrawal response].
AB  - OBJECTIVE: To explore the effects of intrathecal injection of neuronal nitric
      oxide synthase (nNOS) inhibitors 7-Nitroindazole (7-Ni) and inducible nitric
      oxide synthase(iNOS) inhibitors aminoguanidine (AG) on the behavioral changes of
      morphine-induced dependent and withdrawal rats; the expression of Fos, nNOS and
      iNOS in spinal cord. METHODS: To set up morphine dependence model, rats were
      subcutaneously injected with morphine (twice a day, for 5 d). The dose of
      morphine was 10 mg/kg in the first day and was increased by 10 mg/ kg every day.
      On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal
      syndrome was precipitated by an injection of naloxone (4 mg/kg ip). 7-Ni, an nNOS
      inhibitor or iNOS inhibitors AG were intrathecally injected 30 min before the
      administration of naloxone respectively. The scores of morphine withdrawal
      symptom and morphine withdrawal-induced allodynia were observed. One hour after
      naloxone-precipitated withdrawal, Fos protein expression was assessed by
      immunohistochemical analysis and Western blot was used to detect the expression
      of nNOS and iNOS in the rat spinal cord. RESULTS: Intrathecal administration of
      nNOS inhibitor 7-Ni and iNOS inhibitors AG decreased the scores of morphine
      withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited
      the increase of Fos protein expression in the spinal cord of morphine withdrawal
      rats. nNOS and iNOS positive neurons in dorsal horn in nNOS group and iNOS group
      were significantly lower than that in withdrawal group. Compared with withdrawal
      group, level of nNOS and iNOS protein in spinal cord in nNOS group and iNOS group
      were significantly lower. CONCLUSION: It is suggested that nNOS and iNOS in the
      spinal cord may contribute to naloxone-precipitated withdrawal in rats and may
      play different roles in the above-mentioned effect.

PMID- 22860428
TI  - [Progesterone exerts neuroprotective effect on hypoxic-ischemic encephalopathy
      induced brain damage via inhibition expression of inducible nitric oxide synthase
      and nitric oxide production].

PMID- 22860429
TI  - [Protective effects and mechanism of SP600125 on lung ischemia/reperfusion injury
      in rats].
AB  - OBJECTIVE: To investigate the protective effects and mechanism of SP600125
      specificity inhibitor of c-Jun N-terminal kinase (JNK)on lung ischemia
      /reperfusion injury in rats. METHODS: The unilateral lung ischemia/reperfusion
      model was replicated in vivo. Rats were randomly divided into three groups (n =
      10): control group, ischemia/reperfusion group ( I/R group) and
      ischemia/reperfusion + SP600125 group (SP600125 group). The lung tissues sampled
      at the end of each experiment were assayed for wet/dry weight ratio (W/D),the
      injured alveoli rate (IAR), the expression of phosphorylation JNK (p-JNK) and JNK
      protein were detected by Western blot, the expression of Bcl-2, Bax, Caspase3
      protein were detected by immunocytochemistry techniques, the pneumocyte apoptosis
      index (AI) was detected by terminal deoxynucleotidyl transferase mediated dUTP
      nick end abeling(TUNEL), the ultrastructure changes were observed under electron
      microscope. RESULTS: Compared to I/R group, the expression of p-JNK, Bcl-2, Bax
      and caspase-3 protein were markedly decreased (all P < 0.01), the expression of
      Bcl-2 protein and the ratio of Bcl-2/Bax were markedly increased in SP600125
      group(all P < 0.01). The value of AI, W/D, IAR showed significantly lower than
      those in I/R group (all P <0.01). Meanwhile, light morphological and
      ultrastructure injury were found in SP600125 group. CONCLUSION: SP600125 can
      suppress JNK signal pathway, up-regulate the ratio of Bcl-2/Bax to inhibit
      Caspase-3 dependent apoptosis, so that it protects lung tissue from
      ischemia/reperfusion injury.

PMID- 22860430
TI  - [Construction and expression of the recombinant plasmid containing BddhFVIII in
      HepG2 cells].
AB  - OBJECTIVE: To get stable cell line expressing B domain-deleted human FVIII
      (BDDhFVIII) by constructing the eukaryotic expression plasmid. METHODS:
      Eukaryotic expression plasmid containing BDDhFVIII was constructed and
      transfected into HepG2 cells via electroporation. The expression and purification
      of the target protein was detected by Western blot. RESULTS: Results of enzyme
      digestion and sequence analysis demonstrated that the gene of BDDhFVIII was
      correctly inserted into the eukaryotic expression vector pcDNA4/v5-his. Western
      blot confirmed the successful expression of BDDhFVIII at the protein levels in
      HepG2 cells. CONCLUSION: The constructed eukaryotic expression vector was able to
      generate high level expression of human FVIII in HepG2 cells, thus could
      construct human blood coagulation FVIII stable cell line successfully.

PMID- 22860431
TI  - [Effect of L-arginine on pulmonary surfactant and alveolar macrophages in rats
      with pulmonary injury induced by lipopolysaccharide].
AB  - OBJECTIVE: To investigate the effect of L-Arginine (L-Arg) on pulmonary
      surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary
      injury induced by lipopolysaccharide (LPS). METHODS: Model of acute lung injury
      (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD
      rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg
      groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was
      administrated at 3 h or 6 h after LPS injection respectively for 3 h. The
      expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by
      ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was
      detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD
      rats and harvested by selective plating technique. LPS and L-Arg were added to
      the culture medium. The concentration of nitric oxide (NO),the activity of
      lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF
      alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively
      measured. RESULTS: Compared with the control group, the expression of SP-A mRNA
      was significantly decreased, the TP concentration was significantly increased in
      LPS group. Compared with LPS group at the same time points, treatment with L-Arg
      at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased
      markedly, whereas TP concentration was decreased significantly. In cultured rat
      AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were
      significantly increased in LPS group to compared with those of control group. LDH
      activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with
      those of LPS group. CONCLUSION: L-Arg can protect the lung against LPS-induced
      pulmonary injury by up-regulating the expression of PS and inhibiting
      inflammatory transmitters from AM.

PMID- 22860432
TI  - [Changes of circadian rhythms of FDG uptake in C57BL/6 mice brain and heart].

PMID- 22860433
TI  - [The effects of pH0 on electrophysiological properties of VSMCs in brain artery
      of spontaneously hypertensive rats].
AB  - OBJECTIVE: To investigate the effects of pH0 on the electrophysiological
      properties of vascular smooth muscle cells (VSMCs) in brain artery of
      spontaneously hypertension rats (SHR). METHODS: We studied the effects and the
      ion mechanism of pH0 on whole-cell membrane current of VSMCs in brain artery of
      200 - 250 g SHR by whole-cell patch clamp recordings. RESULTS: 1. Acidic pH0
      could inhibit the outward current of VSMCs of brain artery in SHR in a voltage
      dependent manner. It induced a more pronounced inhibition of the outward current
      from 0 to + 60mV; 2. In the presence of 1 mmol/L TEA, the inhibition of acidic
      pH0 on the outward current of VSMCs of brain artery was inhibited. CONCLUSION:
      The changes of outward current of VSMCs of brain artery in SHR induced by pH0 may
      be connected with BKCa channel.

PMID- 22860434
TI  - [Different strength intermittent treadmill training of growth period rats and
      related bone metabolism of the hormone influence].
AB  - OBJECTIVE: To explore the influence of different strength intermittent treadmill
      training of growth period rats on the bone metabolism, so as to provide the
      training intensity of teenagers to set theory support. METHODS: Select 70 male
      four weeks Wistar rats according to body weight randomly divided into seven
      groups (n = 10): the control group and the exercise group. According to the
      VO2max the exercise group was divided into 6 groups: 65%, 70%, 75%, 80%, 85% and
      90% group. Nine weeks treadmill training, training six days a week, each group of
      training three times, each time not less than 10min, the interval was 30 min. The
      last movement after 24 h, took the femur and blood to measured the bone mineral
      density (BMD), bone mass (BMC) and alkaline phosphatase (AKP), resist tartaric
      acid acidic phosphatase (Str-ACP). RESULTS: 1. The femoral BMD (0.1393 +/-
      0.0031), BMC (0.4525 +/- 0.0335) of 70% group were significantly higher than
      those in the control group (BMD: 0.1200 +/- 0.0095, BMC: 0.3238 +/- 0.0485) and
      the other sports group (65% BMD:0.1339 +/- 0.0062, BMC: 0.4058 +/- 0.0492, 75%
      BMD: 0.1296 +/- 0.0015, BMC: 0.3869 +/- 0.0254, 80% BMD: 0.1223 +/- 0.0082, BMC:
      0.3454 +/- 0.0483, 85% BMD: 0.1250 +/- 0.0044, BMC: 0.3731 +/- 0.0381, 90% BMD:
      0.1171 +/- 0.0047, BMC: 0.3051 +/- 0.0286) (P < 0.05), the femoral BMD, BMC of
      90% group were lower than those of the control group, the other in the exercise
      group were higher than those in the control group; 2. Serum AKP in the exercise
      group were significantly higher than those in the control group, the group of 65%
      (41.015 +/- 2.114), 70% (46.035 +/- 2.611), 75% (43.834 +/- 3.155), and 80%
      (38.043 +/- 4.073) were very significantly higher than those in the control group
      (26.875 +/- 1.188) (P < 0.01); 70% group and 75% group were significantly higher
      than those in the 80% group , 85% group and 90% group, while 70% group serum AKP
      level were significantly higher than those in 65% group (P < 0.05), it showed
      that 70% of the VO2 max training intensity of osteoblasts was most active. The
      serum Str-ACP of exercise group were significantly higher than those in the
      control group, along with the increase of the training intensity, serum Str-ACP
      level was rising and the group of 80% (22.430 +/- 1.591), 85% (23.990 +/- 1.870),
      and 90% (28.009 +/- 1.839) serum of Str-ACP were significantly higher than those
      in the group of 65% (18.503 +/- 2.429), 70% (16.447 +/- 2.120) and 75%(17.769 +/-
      1.642) ( P < 0.05), the group of 90% serum Str-ACP were significantly higher than
      those in the group of 80% and 85% (P < 0.05). CONCLUSION: The training of 70% of
      the VO2max, moderate intensity intermittent running, make the growth period rat
      bone mass and bone mineral density to increase obviously.

PMID- 22860435
TI  - [Study on the relation between expression of angiotensin II receptor and
      apoptosis in myocardium in rats of endotoxemia].
AB  - OBJECTIVE: To analyze the expression of angiotensin II (ANG II) receptor and
      apoptosis in myocardium in rats of endotoxemia. METHODS: Model of endotoxemia was
      induced by intraperitoneal injection with lipopolysaccharide (LPS) 10 mg/kg in
      male Wistar rats and saline was injected into control group. The rats were killed
      at 2 h or 6 h after saline (control) or LPS . Expression of the correlation
      factors related to apoptosis of Bcl-2, Bax, AT1 and AT2 receptor in myocardial
      tissue were detected with immunohistochemistry (IHC), and changes of myocardial
      cells apoptosis was detected by the method of TUNEL. The gene expression of AT1
      and AT2 receptor was examined by RT-PCR. The pathological changes of myocardial
      tissue were observed by electron microscope. RESULTS: Compared with control group
      , the expression of AT1 and AT2 receptor were significantly decreased, especially
      in 6 h group; and the expression of Bcl-2 and Bax were decreased, the ratio of
      Bcl-2/Bax had the downtrend as well as the apoptosis of myocardial cells.
      CONCLUSION: Interfered by LPS, the down regulation of AT1 and AT2 receptor
      expression has the negative relation with apoptosis of myocardial cells, this
      result indicated that down regulation of AT1 and AT2 receptor expression maybe
      related to cardiac functional impairment, which maybe help us to find a new
      protective path to prevent myocardial damage induced by systemic inflammatory.

PMID- 22860436
TI  - [Protective effect of silymarin on liver injury in mice induced by carbon
      tetrachloride].

PMID- 22860437
TI  - [Preventive effects of Salvia miltiorrhiza on multiple organ edema in the rats of
      limb ischemia/reperfusion].
AB  - OBJECTIVE: To investigate the preventive effects of Salvia miltiorrhiza (SM) on
      multiple organ edema in the rats which suffered from hind limb
      ischemia/reperfusion( LI/R). METHODS: Twenty four Wistar rats were randomly
      divided into 3 groups (n = 8): control group (C group), ischemia/reperfusion
      group (I/R group ), Salvia miltiorrhiza group (SM group). Referring to Tourniquet
      method, the model rats which underwent 4 hours ischemia and 4 hours reperfusion
      of hind limbs were made. Thirty minutes before reperfusion, SM was given to the
      rats in SM group by tail vein injection at the dose of 5 mL/kg. Accurately
      weighed one gram of heart, liver, kidney, lung, brain, intestine and skeletal
      muscle from every animals, weigh these specimens after baking (60 degrees C, 55
      hours), calculated the ratio of wet and dry (Wet/Dry,W/D). The levels of
      interleukin-1 (IL-1) ,interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF
      alpha) in plasma and the contents of Superoxide dismutase (SOD) and malonaldehyde
      (MDA) were measured. The morphologic changes of skeletal muscle were observed
      with microscope. RESULTS: It was found that after suffering from
      ischemia/reperfusion, the W/D of every specimens increased in different degree (P
      < 0.05, P < 0.01). In plasma, the values of SOD decreased but MDA increased
      obviously (P < 0.05, P < 0.01). The levels of IL-1, IL-6 ,TNF-alpha-a in plasma
      increased (P < 0.05, P <0.01). After LI/R, infiltration of inflammatory cells,
      broaden interstitial around muscle fiber and disordered arrangement of muscle
      fibers could be seen under microscope. However, Compared with LI/R group, W/D and
      levels of serum inflammatory factors in SM group were all lower, the values of
      SOD in plasma increased but MDA in plasma failed down. Pathological changes in
      skeletal muscle were improved. CONCLUSION: Limb ischemia/reperfusion can lead to
      multiple organ edema, Salvia miltiorrhiza can prevent the edema in some degree by
      anti-oxidation and anti-inflammation.

PMID- 22860438
TI  - [Construction of the skeletal muscle-specific TbetaR II knockout mice].
AB  - OBJECTIVE: To generate the skeletal muscle-specific transforming growth factor
      beta receptor II (TbetaR II) gene knockout mice for the research on the function
      of the TbetaR II gene in skeletal muscles. METHODS: TbetaR II (flox/flox) mice
      were generated using embryonic stem cell technology. The MCK-Cre mice were
      engineered containing Cre recombinase under the control of creatine kinase (MCK)
      muscle-specific promoter. TbetaR II (flox/flox) mice were crossed with MCK-Cre
      mice generating TbetaR II (flox/flox)/MCK-Cre double Tg mice. And then, TbetaR II
      (flox/wt) /MCK-Cre(+) double Tg mice were crossed with TbetaR II (flox/flox) mice
      to generate TbetaR II (flox/flox)/MCK- Cre(+) mice genetically ablating TbetaR II
      in cre-expressing skeletal muscle cells. RESULTS: As predicted, mice lacking
      TbetaR II by gene targeting in skeletal muscles were generated first in the world
      using Cre/loxP system. TbetaR II null mutant mice were viable, fertile and showed
      apparently normal development.

PMID- 22860439
TI  - [Preliminary study in glycyrrhizin content and its influencing factors of wild
      and cultivated in different region of China].
AB  - OBJECTIVE: In order to understand the glycyrrhizin content range in the wild and
      cultivated Glycyrrhiza uralensis in China and to find the related influencing
      factors of glycyrrhizin content. METHOD: The glycyrrhizin content of 165 wild and
      1 013 cultivated G. uralensis samples from 37 countries in 9 provinces was
      determined by HPLC, and the effects of the producing region, medicinal parts,
      cultivation years, soil type and texture on the glycyrrhizin content were
      analyzed. RESULT AND CONCLUSION: The average glycyrrhizin content was (4.43 +/-
      1.32)% in the wild G. uralensis population, and (1.51 +/- 0.49)% in the
      cultivated and the glycyrrhizin content in the cultivated was less than the
      minimum sandards in the Chinese Pharmacopoeia. The glycyrrhizin content was
      significant different in the wild and cultivated G. uralensis in different
      producing regions, respectively. The glycyrrhizin content in roots and rhizome of
      the wild G. uralensis had no significant difference, it had no significant
      difference in the cultivated G. uralensis from 1 to 4 years and it increased
      rapidly after 5 years, and the effects of the soil types and texture on it were
      significant.

PMID- 22860440
TI  - [Effects of water stress and nitrogen nutrition on regulation of Catharanthus
      roseus alkaloids metabolism].
AB  - OBJECTIVE: Under various drought conditions and nitrogen application, the content
      of vindoline, catharanthine, vincristine and vinblastine in the leaf of
      Catharanthus roseus were illustrated to improve the content of alkaloid
      theoretically. METHOD: Six groups were set in the experiment, which included: CK
      (natural control), CN (natural control + nitrogen), LK (low drought), LN (low
      drought + nitrogen), HK (high drought), HN (high drought + nitrogen) to discuss
      the change characteristics of total nitrogen, the activity of alkaline POD and
      TDC, the content of four alkaloids under the different conditions were measured.
      RESULT: Under LK condition, the activity of POD, TDC were enhanced. In the early
      stage of stress (0-21 d), vindoline, catharanthine, vincristine and vinblastine
      accumulated, and reduced in the later stage (28-35 d). For all groups, adding
      exogenous nitrogen could improve the total content of nitrogen, vindoline and
      vinblastine, meanwhile the activity of POD and TDC were enhanced as well. The LN,
      HN treatments were beneficial to accumulating catharanthine and vinblastine.
      CONCLUSION: Drought stress or additional nitrogen have an influence on both of
      the activities of POD and TDC, and the four alkaloids were affected as well.
      Thereinto, the LN condition was the most effective treatment for accumulating the
      four alkaloids (vindoline, catharanthine, vincristine and vinblastine), which
      were regulated by improve nitrogen content and enzymatic activity.

PMID- 22860441
TI  - [Ethno-pharmacological investigation of Schisandraceae plants in China].
AB  - OBJECTIVE: To investigate and arrange the ethno-pharmacological information of
      Schisandraceae plants in China. METHOD: The information was obtained by
      literature search, specimen inspection, field resource investigation and samples
      collection. RESULT: Twenty-six Schisandraece plants (inlcuding 4 varieties) have
      been used as folk medicines in different regions of China, the identical
      medicinal parts of different species in one genus show the similar usage, action
      and indications, and different medicinal parts with different administrated ways
      show different action and indications. CONCLUSION: The results provide reliable
      information for resource development and comprehensive utilization of
      Schisandraece plant resource in China.

PMID- 22860442
TI  - [Determination of podophyllotoxin and total lignans in Sinopodophyllum emodi].
AB  - OBJECTIVE: To determine the content of podophyllotoxin and total lignans in
      Sinopodophyllum emodi Ying from different areas and evaluate the resource
      utilization of this endangered medicinal plant. METHOD: HPLC and UV
      spectrophotometry were used to determine the content of podophyllotoxin and total
      lignans in 126 samples from different habitats and the total lignans content was
      determined by the reference wavelength method. RESULT: According to the results,
      the highest content was determined from the samples from Yongdeng Nature Reserve
      in Gansu province, and the lowest ones was found in the samples from Tibet. The
      former's podophyllotoxin and total lignans contents were 7.40% and 20.66%,
      respectively, which were 19 times and 4 times more than those of the latter. The
      content of podophyllotoxin and total lignans in S. emodi were significantly
      positively related, meanwhile, samples from both low altitude and high latitude
      showed the higher content. CONCLUSION: The two determination methods are simple,
      rapid, accurate and repeatable. It is more scientific and rational to evaluate
      the resource utilization of S. emodi with two indicators, those are the content
      of podophyllotoxin and the content of total lignans. This paper is instructive to
      the collection of wild resources and the establishment of production bases.

PMID- 22860443
TI  - [Seed quality test methods of Oldenlandia diffusa].
AB  - OBJECTIVE: To optimize the testing methods for seed quality, and provide basis
      for establishing seed testing rules and seed quality standard of Oldenlandia
      diffusa. METHOD: According to the related seed testing regulations, the seed
      quality of O. diffusa from different producing areas was measured. RESULT AND
      CONCLUSION: The testing methods for seed of O. diffusa was established, including
      sampling, purity analysis, weight per 1 000 seeds, seed moisture content, seed
      viability and percentage germination.

PMID- 22860444
TI  - [Chloroplast ultrastructure and photosynthetic characteristics of five kinds of
      dandelion (Taraxacum) leaves in northeast China].
AB  - The paper adopted the JEM-100CX II transmission electron microscope to observe
      chloroplast ultrastructure of five kinds of dandelion (Taraxacum) leaves in
      northeast, and the LI-6400 portable photosynthesis system was used to compare the
      chlorophyll fluorescence and the photosynthesis characteristics of five kinds of
      dandelions in Northeast China. Chloroplast ultrastructure showed: in the five
      kinds of dandelion, larger chloroplast, grana with more layers, regular
      thylakoid, without starch grains and so on, these chloroplasts characteristics
      decided to bigger photosynthetic rate. The five kinds of dandelion P(n) exhibited
      a "double peak" diurnal curve: stomatal limitation is the main adjustment factors
      for the midday depression phenomenon. The P(n),G(s),C(i) content of T. mongolicum
      are the highest, and T. asiaticum are the lowest among them. The relation between
      P(n) and G(s),C(i) is direct ratio, P(n) and T(r) is in an inverse proportion
      among the five kinds of dandelion. In addition, P(n) is positively correlated
      with Chla, Chlb, and the relationship with Chlb is bigger. The paper demonstrates
      the Mongolian dandelion photosynthetic efficiency is the highest, it is an higher
      photosynthetic efficiency dandelion,it provide theoretical basis for assessment
      and use of the resource of dandelion.

PMID- 22860445
TI  - [Modification and stability of ginsenoside Rg1PEG].
AB  - OBJECTIVE: To study the stability of ginsenoside Rg1 before and after being
      modified by PEG (PEG-Rg1) in isolated rat stomachs. METHOD: SD rats, after 18 h
      of fasting, were randomly divided into the Rg1 group and the PEG-Rg1 group. Rg1
      stomach perfusion fluid and PEG-Rg1 infusion fluid were accurately extracted and
      injected into their stomachs in vitro, with oscillation at 37 degrees C. Samples
      were taken in different time points and contents of ginsenoside Rg1 were
      determined by UPLC to observe and compare the stability of ginsenoside Rg1 and
      PEG-Rg1 in rat stomachs in vitro. RESULT: Rg1 in rat stomachs showed poor
      stability, Rg1 was measured to be 26.8% in 2 h, with degradation of 73.2%. Its
      stability in PEG-Rg1 was improved in rat stomachs, Rg1 was measured to be 81.8%
      in 2 h, with degradation of only 18.2%. CONCLUSION: PEG-modified ginsenoside Rg1
      can enhance the stability of ginsenoside Rg1 in stomach and improve degradation
      and poor stability of ginsenoside Rg1 in stomach.

PMID- 22860446
TI  - [Study on solid dispersion of binary vector of tanshinone II A].
AB  - OBJECTIVE: To prepare the solid dispersion of tanshinone II A (TS II A) by the
      combined application of nano-silica and poloxamer 188 (F68), in order to observe
      its dissolution and stability. METHOD: Tanshinone II A solid dispersion was
      prepared by the solvent method with nano-silica and poloxamer 188 as binary
      vectors. Its physical characteristics, in vitro dissolution and stability were
      further assessed. RESULT: The tanshinone II solid dispersion was prepared with
      the weight ratio of nano-silica and poloxamer 188 of 1: 3. The differential
      scanning calorimetry (DSC) demonstrated that Tanshinone II A existed in vectors
      as amorphous state. The in vitro dissolution of tanshinone II A solid dispersion
      is up to 90% at 60 min. Accelerating experiment showed that content and in vitro
      dissolution of tanshinone II A solid dispersion did not change after storage over
      3 months. CONCLUSION: Solid dispersion of binary vector of tanshinone II A can
      obviously improve the dissolution and stability of tanshinone II in practice.

PMID- 22860447
TI  - [Study on optimization method of dynamic extraction process].
AB  - OBJECTIVE: To establish a new optimized extraction process based on dynamic
      changes in extract concentration during the extraction process. METHOD: Sanqi was
      taken as an example to compare the concentration of marker components, total
      solids yield and similarity evaluation of the fingerprint images of extracts by
      orthogonal design optimization process and dynamic optimization process to assess
      the feasibility of dynamic process optimization method. RESULT: The concentration
      of marker components and total solids yield vary less than 5%, with a 100% of
      similarity in fingerprints, indicating basic coincidence between extracts by the
      two optimized processes. The dynamic process optimization process could save 79%
      of the extraction time. CONCLUSION: In the extraction time, the dynamic
      optimization process is superior to the orthogonal design optimization process in
      that it can significantly reduce the extraction time and lower production costs.

PMID- 22860448
TI  - [Spectroscopic study on interaction between cistanoside F and bovine serum
      albumin].
AB  - OBJECTIVE: To study the conjugation reaction characteristics of caffeic acid
      micromolecule cistanoside F and bovine serum albumin. METHOD: The interaction
      between bovine serum albumin (BSA) and cistanoside F that was separated from
      Callicarpa plant for the first time and abbreviated CF was detected by
      fluorescence (FS), UV-vis absorbance and circular dichroism (CD) under simulative
      physiological conditions. RESULT: CF-BSA's static apparent binding constant
      (K(a)), number of binding sites (n), efficiency of energy transfer (E), spatial
      distance (r), thermodynamic parameters deltaG, deltaH and deltaS and changes in
      alpha-helical structure content in BSA before and after CF's effect were
      calculated to define the binding site of CF in BSA and analyze the impact of
      several common metal ions on the interaction of CF and BSA. CONCLUSION: Ground
      state compounds formed by CF and BSA could cause intrinsic fluorescence
      quenching. Their binding constant K(a) of cistanoside F with BSA was 4.36 x 10(4)
      L x mol at 25 degrees C, the number of binding site n was 1, and the spatial
      distance r was 3.09 nm. The results indicated that the hydrogen bond played a
      major role in cistanoside F-BSA association. The displacement experiments
      confirmed that cistanoside F can bind to site I of BSA. In addition, the binding
      constant of cistanoside F with BSA was enhanced after the addition of some common
      metal ions Mg2+, Fe3+, Cu2+ and Zn2+. The intrinsic fluorescence of BSA was
      quenched by cistanoside F via forming cistanoside F-BSA complex and non-radiation
      energy transfer. CD spectra showed that the binding of cistanoside F with BSA
      induced conformational changes in BSA.

PMID- 22860449
TI  - [Chemical constituents from Sambucus chinensis].
AB  - Five compounds were separated from Sambucus chinensis and identified as maslinic
      acid(1), 12alpha, 13-dihydroxyolean-3-oxo-28-oic acid(2), 13-hydroxyolean-3-oxo
      28-oic acid (3), 3-oxo oleanolic acid (4), corosolic acid (5). Of them,compound 3
      was a new compound, and compounds 1, 2, 4, and 5 were seperated from this plant
      for the first time.

PMID- 22860450
TI  - [Chemical constituents of Phymatopteris hastate and their antioxidant activity].
AB  - OBJECTIVE: To study chemical constituents contained in Phymatopteris hastate and
      their antioxidant activity. METHOD: Chemical constituents were separated and
      purified from P. hastate by using such methods as silica gel, Toyopearl HW-40C
      and HPLC preparative chromatography. Their structures were identified by
      spectroscopic methods such as NMR. Furthermore, 1, 1-diphenyl-2-picryl
      hydrazyl(DPPH) method was used to assess the antioxidant activity of each
      compound. RESULT: Fourteen compounds were separated and identified as 4-O-beta-D
      glucopyranosyl-ethyl-trans-caffeicate (1), kaempferlo-7-O-alpha-L-rhamnopyranside
      (2), kaempferol-3, 7-di-O-alpha-L-rhamnopyranoside (3), kaempferol-3-O-alpha-L
      arabinofuranosyl-7-O-alpha-L-rhamnopyranoside (4), juglanin (5), naringin (6),
      naringenin-7-O-beta-D-glucopyranoside (7), trans-caffeic acid (8), trans-caffeic
      acid-3-O-beta-D-glucopyranoside (9), trans-cinnamic acid-4-O-beta-D-
      glucopyranoside (10), trans-melilotoside (11), cis-melilotoside (12), ethyl
      chlorogenate (13), protocatechuic acid (14). The antioxidation experiment showed
      an obvious antioxidant activity in compounds 1-9, 13-14. CONCLUSION: All of the
      compounds were separated from this genus for the first time. Among them, compound
      1 was not seen in literature reports and assumed to be a new artifact derived
      from compound 9 and ethanol. Compounds 1-9, 13-14 showed a remarkable antioxidant
      activity.

PMID- 22860451
TI  - [Alpha-glucosidase inhibitory active constituents contained in nutshell of Trapa
      acornis].
AB  - OBJECTIVE: To study chemical constituents in nutshell of Trapa acornis and in
      vitro inhibitory activity against alpha-glucosidase. METHOD: EtOAC and n-butanol
      extractive fractions were separated by chromatography and their structures were
      identified by multiple spectroscopic techniques. RESULT: Nine compounds were
      separated, they were 4,23,24-trimethylcholest-22-en-3-ol (1), stigmasterol (2),
      alpha-amyrin (3), (+)-nyasol (4), oleanolic acid (5), ursolic acid (6),
      hederagenin (7), 3,23-dihydroxy-12-ursen-28-oic acid (8) and beta-daucosterol
      (9). Total extracts from T. acornis nutshells, petroleum ether fractions, acetic
      ether fractions and normal butanol fractions showed inhibitory activity against
      alpha-glucosidase. Compound 5 (IC50 2.88 mg x L(-1)) and 6 (IC50 4.42 mg L(-1))
      showed stronger inhibitory activity against alpha-glucosidase. CONCLUSION: All
      compounds except compound 2 were separated from the genus for the first time, and
      compound 1-9 were separated from this plant for the first time.

PMID- 22860452
TI  - [Chemical constituents from Gueldenstaedtia stenophylla].
AB  - OBJECTIVE: To study chemical constituents of aerial parts of Gueldenstaedtia
      stenophylla. METHOD: Chemical constituents were extracted with 95% alcohol and
      separated by repeated silica gel column, MCI, Sephadex LH-20 and RP C18 column
      chromatographic separation from aerial parts of G. stenophylla. Their structures
      were identified on the basis of the physiochemical properties and spectral data.
      RESULT: Twenty-two compounds were separated and identified as apigenin (1),
      chrysoeriol (2), farnisin (3), diosmetin (4), 4', 7-dihydroxyflavone (5),
      luteolin (6), 3', 4', 7-trihydroxyflavone (7), quercetin (8), m-hydroxy benzoic
      acid (9), trans-ferulic acid (10), isovanillic acid (11), E-beta-hydroxy-cinnamic
      acid (12), salicylic acid (13), trans-p-coumaric acid (14), protocatechuic acid
      (15), (S) -2-hydroxyphenylpropionic acid (16), esculetin (17), 7-methoxy coumarin
      (18), phaseic acid (19), blumenol A (20), (6S, 9R)-roseoside (21), kaempferol-7-O
      alpha-L-rhamnopyranoside (22). CONCLUSION: Except compounds 1, 5, 8 and 15, the
      rest compounds were separated from genus Gueldenstaedtia for the first time.

PMID- 22860453
TI  - [Chemical constituents from the seed coat of Juglans regia].
AB  - Fifteen compounds were isolated from the seed coat of Juglans regia by silica
      gel, MCI gel and Sephadex LH-20 gel column chromatography, as well as high
      preparative performance liquid chromatography. Their structures were identified
      as salidroside (1), (6S, 9S)-roseoside (2), (6S, 9R)-roseoside (3), blumenol C
      glucoside (4), byzantionoside B (5), 5-hydroxy-2-methoxy-1, 4-naphthoquinone (6),
      gallic acid (7), glycerol 1-(9Z-octadecenoate)-2-(9Z, 12Z-octadecadienoate)-3
      (9Z, 12Z, 15Z-octadecatrienoate) (8), glycerol 1, 2, 3-tri-(9Z, 12Z
      octadecadienoate) (9), glycerol 1, 2, 3-tri-(9Z, 12Z, 15Z-octadecatrienoate)
      (10), glycerol 1-hexadecanoate-2, 3-di-(9Z, 12Z-octadecadienoate) (11) on the
      basis of EI-MS, FAB-MS and NMR spectra. Moreover, 35 volatile compounds were
      identified by GC-MS.

PMID- 22860454
TI  - [Chemical constituents contained in Populus tomentosa].
AB  - OBJECTIVE: To separate and identify chemical constituents from stem barks of male
      plants of Populus tomentosa. METHOD: Fresh stem barks of P. tomentosa were
      extracted with methanol to obtain extracts which were suspended in water and
      blended successively with petroleum ether, ethyl acetate and n-butanol. Various
      chromatographic techniques were used to separate and purify the constituents
      extracted with ethyl acetate and n-butanol fractions. Their structures were
      identified on the basis of their physicochemical properties and spectral data.
      RESULT: Twelve compounds were separated with ethyl acetate and n-butanol
      fractions and identified as benzoic acid (1), daucosterol (2), tremuloidin (3),
      rhamnocitrin (4), sakuranetin (5), 7-O-methylaromadendrin (6), isograndidentatin
      A (7), siebolside B (8), sakuranin (9), micranthoside (10), alpha-D-glucopyranose
      (11), and sucrose (12). CONCLUSION: Compounds 4-12 were separated from this plant
      for the first time. Of them, compound 10 was separated from this plant genus for
      the first time.

PMID- 22860455
TI  - [Rapid detection of alkaloids in Ipecac by direct analysis in real time tandem
      mass spectrometry (DART-MS/MS)].
AB  - OBJECTIVE: To detect alkaloids in Ipecac by direct analysis in real time tandem
      mass spectrometry (DART-MS) without pre-treatment and chromatographic separation.
      METHOD: Under the optimum conditions, DART-MS characteristic spectra were
      collected for tablet of Ipecac powder, Ipecac stems and leaves by full scanning,
      and secondary spectra were adopted for identifying alkaloids. The multiple
      reaction monitoring mode was adopted to determine the mass spectrum peak
      intensity of determinands on the surface of determined samples, in order to
      calculate their average content in samples. RESULT: Spectra of tablet of Ipecac
      powder and Ipecac stems showed remarkable ionized ion peaks of emetine and
      cephaeline at m/z 481 and 467, while spectra of leaves showed ionized ion peaks
      of other alkaloids at m/z 479 and 465. Furthermore, the quantitative analysis was
      also demonstrated with good reproducibility and linear relationship. CONCLUSION:
      The mode can play a role in rapid determination of medicinal materials and
      prepared herbal medicines and real-time rapid quantitative analysis on
      intermediates and preparations.

PMID- 22860456
TI  - [Determination of alpha-pinene and octyl acetate contents in Boswellia serrata].
AB  - OBJECTIVE: To establish method for determining the contents of alpha-pinene and
      octyl acetate in Boswellia serrata, in order to provide preference for making
      quality standards for B. serrata and processed B. serrata. METHOD: Application of
      orthogonal design was employed to optimize the solvent, solvent quantity and
      extraction time. The GC-MS analysis was performed on a Rxi-5ms silica capillary
      column, running in the electron impact (EI) mode, with ion trap and injector
      temperature of 200 degrees C and 250 degrees C, respectively. The column oven was
      initially 50 degrees C and was held for 1 min after injection, followed by
      temperature ramping at 5 degrees C x min(-1) up to 130 degrees C, holding for 1
      min. 1 microL of samples solution were injected in the split mode (1:60). Helium
      was the carrier gas. The mass spectrometer was set to scan m/z 45450 with an
      ionizing voltage at 70 eV. RESULT: Sample solutions were prepared for 50-fold
      dose by ultrasonic extraction with hexane for 30 min. The content of alpha-pinene
      and octyl acetate in 10 batches of B. serrata were 0.021 3-0.149 5, 2.519 6-9.098
      0 mg x g(-1), respectively. And, those of alpha-pinene and octyl acetate in
      processed B. serrata were 0.015 9-0.065 9, 0.801 0-12.812 2 mg x g(-1).
      CONCLUSION: The method is a stable and reliable for determining the contents of
      alpha-pinene and octyl acetate in B. serrata.

PMID- 22860457
TI  - [Therapeutic effect of nux vomica total alkali gel on adjuvants arthritis rats].
AB  - OBJECTIVE: To observe the therapeutic effect and mechanism of nux vomica total
      alkali gel (NVTAG) on adjuvants arthritis (AA) rats. METHOD: SD rats were
      randomly divided into nine groups: the normal group, the AA model group, NVTAG
      high, middle and low-dose (25, 12.5, 6.25 mg x kg(-1)) groups and the Votalin
      control (diclofenac diethylamine emulgel, 50 mg x kg(-1)) group. Except for the
      normal group, the remaining groups were transcutaneously administered with 0.1 mL
      freund's adjuvant complete (FCA) for inflammation in left rear feet and then
      evenly treated with medicine and packed with oilpapers. The foot volume method
      was adopted to determine foot swelling degree, with pain scoring and
      polyarthritis scoring. HE staining was used to observe arthro-pathologic injury.
      The content of prostaglandin E2 (PGE2), interleukin-1 (IL-1), IL-6, tumor
      necrosis factor (TNF-alpha) and vascular epidermal growth factor (VEGF) in
      synovium homogenates were measured by enzyme-linked immuno-absorbent assay
      (ELISA) respectively. RESULT: Compared with the model group, NVTAG and control
      gel can obviously reduce the foot swelling degree, polyarthritis indicators and
      relieve arthro-pathologic injury in AA rats (17-21 d). The levels of IL-1, PGE2,
      IL-6, VEGF and TNF-alpha in synovial homogenates of AA rats were also reduced by
      NVTAG significantly. CONCLUSION: NVTAG shows an antergic effect on AA progress in
      rats, which is closely related to inhibition of development of inflammatory
      mediator.

PMID- 22860458
TI  - [Comparative study on tumor cell apoptosis in vitro induced by extracts of
      Stellera chamaejasme].
AB  - OBJECTIVE: To in vitro compare the induction of extracts of Stellera chamaejasme
      ESC, ESC-1 and ESC-2 on NCI-H157 cell apoptotic. METHOD: The apoptosis rate was
      inspected by flow cytometry; caspase-3, 8, 9 activities was measured by
      spectrophotometry. Fas, Fas-L, TNF-alpha, Trail-R, Cyto-C, Smac/diablo protein
      expressions of apoptosis pathway was observed by Elisa method. RESULT: Compared
      with the control group, ESC, ESC-1, ESC-2 can significantly improve the apoptosis
      rate of NCI-H157 cell. ESC significantly improved cells caspase-3, 8 activity,
      ESC-2 can significantly improve the activity of caspase-3, 8, 9. ESC, ESC-1, ESC
      2 significantly increased Fas expression and ESC significantly increased Fas/Fas
      L ratio. ESC, ESC-1, ESC-2 significantly increased TNF-alpha protein expression.
      ESC-1 significantly lowered TRAIL-R expression. ESC, ESC-1, ESC-2 had no
      significant effect on Cyto-C. ESC-1, ESC-2 significantly reduced Smac protein
      expression. CONCLUSION: The apoptotic effect induced by ESCs may be related to
      the regulation of death receptor pathway proteins. Induction mechanisms of ESCs
      were so complicated that it may have a two-way regulatory effect. Its induction
      in apoptosis is a result from comprehensive regulation and control.

PMID- 22860459
TI  - [Study on hepatotoxicity of aqueous extracts of Polygonum multiforum in rats
      after 28-day oral administration-analysis on correlation of cholestasis].
AB  - OBJECTIVE: To observe the liver injury degree of SD rats after 28-day
      administration of aqueous extracts of Polygonum multiflorum (AEPM) and the
      correlation with cholestasis mechanism. METHOD: Adult SD rats were orally
      administered with 30, 60 g x kg(-1) of APEM once every day for 28 d. After 28 d,
      the general condition of rats such as weight were observed, liver function
      related indicators were detected. Bile was collected to determine total bile acid
      output, flow rate and density and changes in major compositions. Their livers
      were weighed then sent for histopathological examination. RESULT: AEPM did not
      change the general conditions and weights of rats. From the results of the
      related indicators of liver function and cholestasis, AEPM did not change the
      contents of ALT and AST in serum, but high dose of AEPM can increase the contents
      of ALP, GGT and TBA in serum (P < 0.05, P < 0.01) and decrease the content of
      TBIL in serum (P < 0.05). And the contents of GGT in serum of low dose rats were
      increased (P < 0.05). The bile flow was not changed by AEPM, but bile
      compositions of high dose male rats were obviously changed (TG increase, TBIL
      decrease, TBA decrease). The weights of liver and ratio of liver of the high dose
      rats were increased but showed no statistical significance. Pathologic
      examination displayed that there were only small pieces of necrosis in livers of
      several rats, without any severe disease. CONCLUSION: AEPM can obviously injure
      bile duct epithelial cells, intervene liver cell functions and change bile
      compositions in rats, thus it is proved to induce cholestasis without severe
      liver injury.

PMID- 22860460
TI  - [Regulation trend of resveratrol on TNFalpha-,IL-1beta, IL-6 expressions in
      bronchoalveolar lavage fluid of RSV-infected BALB/c mice].
AB  - OBJECTIVE: To study the regulation trend of resveratrol on TNF-alpha, IL-1beta,
      IL-6 expressions in bronchoalveolar layage fluid (BALF) of RSV-infected BALB/c
      mice at different time points. METHOD: RSV-induced BALB/c mice were orally
      administered with resveratrol. Their BALFs were collected at 24, 72 and 144 h
      after the first nasal drip with RSV to detect the level of TNF-alpha, IL-1P3, IL
      6 by EILSA. RESULT: The expression of TNF-alpha, IL-1Pf and IL-6 in BALF
      increased significantly compared with the normal group (P <0. 01) after 24 hours
      of RSV infection, while the expression of TNF-alpha (P < 0.01), IL-1beta (P <
      0.05), IL-6 (P < 0.01) in the resveratrol group decreased notably compared with
      the model group. After 72 hours of infection with RSV, although the expression of
      TNF-alpha (P < 0.05), IL-1beta (P < 0.01) and IL-6 (P < 0.01) in BALF in model
      group were higher than those in the normal group, they were much more lower than
      at 24 h. The expression of IL-1beta and IL-6 (P < 0.05) in the resveratrol groups
      were down-regulated significantly, but no difference had been shown in TNF-alpha
      expression compared with the RSV infection group. After infection with RSV for
      144 h, the expression of IL-1beta (P < 0.01) and IL-6 (P < 0.05) in BALF in the
      model group were higher than those in the normal group, but there was no
      difference in the secretion of TNF-alpha. The expression of TNF-alpha, IL-1beta
      and IL-6 showed also no remarkable difference between the resveratrol groups and
      the RSV infection group. CONCLUSION: Resveratrol can inhibit the over expression
      of inflammatory factors TNF-alpha, IL-1beta, IL-6 in bronchoalveolar lavage fluid
      of RSV-induced BALB/c mice and keep them at a low level with the passing of
      infection time.

PMID- 22860461
TI  - [Study on impact of vinegar processing on toxic effect of Stellera chamaejasme].
AB  - OBJECTIVE: To study the scientific theory on detoxification (attenuation) of
      Stellera chamaejasme (ScL) by processing and the impact on drug effect of ScL
      before and after being processed with vinegar. METHOD: The difference in
      ingredients of ScL before and after being processed vinegar was compared by using
      PHLC-MS technique. A subcutaneously transplanted tumor model of H22 hepatoma was
      established to compare the lethal effect and weight change between tumor-loaded
      mice and normal mice. After consecutive oral administration in tumor-loaded mice,
      the impacts on tumors and immune organs were compared before and after being
      processed with vinegar. Luciferase Report Gene was employed to investigate the
      target genes TGF-beta, AP1 and NF-kappaB. RESULT: The LD50 (median fatal dose) of
      extract Zp1102 exhibited higher than that of the processed one Zp1103, that is 9.
      89 g x kg(-1) vs. 16.85 g x kg(-1). According to the test, Zp1102 showed more
      effective anti-tumor activities in vivo than that of Zp1103 in a same dosage,
      with the tumor inhibitory rate 36.24% (P < 0.01) at the dosage of2 g x kg(-1) and
      34.40% (P < 0.05) at the dosage of 1 g x kg(-1). At the dosage of 1 g x kg(-1),
      Zp1102 showed a tumor inhibitory rate of 34.52% (P < 0.05), much higher from
      21.55% in Zp1103. Both Zp1102 and Zp1103 had basically no impact on the report
      gene NF-kappaB, besides that Zp1102 up-regulated the report gene after increase
      in NF-kappaB concentration and down-regulated TGF-beta, but Zp1103 can only up
      regulate NF-kappaB expression without any impact on TGF-beta. CONCLUSION:
      Processed ScL extracts show less toxic than unprocessed extracts and slight
      reduction in anti-tumor activity, which may be related to the regulation of
      transforming growth factor TGF-beta.

PMID- 22860462
TI  - [Effect of Lycium ruthenicum anthocyanins on atherosclerosis in mice].
AB  - OBJECTIVE: To study the effect of Lycium ruthenicum anthocyanins on
      atherosclerosis (AS) in mice. METHOD: Normal mice were taken as the control
      group, and hyperlipemia mice were divided into the model group, Lycium ruthenicum
      anthocyanins low, medium and high dose groups, and the simvastatin drug control
      group. After the oral administration, blood lipid indicators were detected by
      enzymatic analysis. The histomorphological changes in aortas, hearts and livers
      were observed, and liver-related indicators were determined by using hematoxylin
      eosin (HE) staining. RESULT: Compared with the high-fat group, L. ruthenicum
      anthocyanins low, medium and high dose groups showed significant decrease in
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol
      (LDL-C) and atherosclerotic index (AI) (P < 0.05). However, high-density
      lipoprotein cholesterol (HDL-C) level showed a trend of higher than the model
      group. Liver's total antioxidant capacity (T-AOC), Glutathione peroxidase (GSH
      PX), lipoprotein lipase (LPL) were significantly increased (P < 0.05),
      malondialdehyde (MDA) was markedly decreased (P < 0.01); the percentage of aortic
      plaque area of each anthocyanins dose group in the total area was significantly
      lower than the model group (P < 0.05); severity of aorta, heart and liver were
      significantly lighter than the high-fat group. But the media dose group was
      similar with the simvastatin group. CONCLUSION: L. ruthenicum anthocyanins can
      interfere the formation of AS, while lowering blood lipid levels in mice.

PMID- 22860463
TI  - [Raman spectroscopic study on effect of danshen injection on human erythrocyte
      membranes and its mechanism].
AB  - OBJECTIVE: Danshen, as a traditional Chinese medicine for promoting blood
      circulation and removing blood stasis, is widely applied in improving human
      erythrocyte deformability in clinics. But its direct effect on erythrocyte
      membranes is still unclear. METHOD: In this essay, the confocal Raman technique
      was adopted to measure the changes in Raman spectra of human erythrocytes before
      and after the administration of Danshen injection. RESULT: The results showed
      slight changes in group conformations corresponding to erythrocyte membranes
      after the administration of danshen injection. Specifically, 1064, 1126 cm(-1)
      spectral lines attributed to phospholipid molecule acyl C-C skeleton anti
      conformation were obviously weakened, whereas 1091 cm(-1) spectral line
      attributed to phospholipid molecule acyl C-C skeleton guache conformation notably
      intensified. Besides, the longitudinal order-parameter in chains (Strans) of
      phospholipids was reduced significantly. CONCLUSION: Danshen injection can
      transfer erythrocyte membrane phospholipid molecule acyl C-C skeleton anti
      conformation to guache conformation, indicating the increase in liquidity of
      erythrocyte membrane phospholipids and erythrocytes. Danshen injection's effect
      in improving erythrocyte membrane structure and function may be the intrinsic
      mechanism for its pharmacological effect as a traditional Chinese medicine.

PMID- 22860464
TI  - [Effect of catalpol and puerarin freeze-dried powder on coagulability,
      hemorheology and no in rats with Qi-deficiency and blood-stasis syndrome].
AB  - OBJECTIVE: To study the effect of catalpol and puerarin freeze-dried powder for
      injection (CPFPI), a new compound traditional Chinese medicine (TCM) preparation,
      on coagulability, hemorheology and NO in rats with qi-deficiency and blood-stasis
      syndrome. METHOD: The model of rats with qi-deficiency and blood-stasis syndrome
      was established by hunger, fatigue, cold-dampness, panic and high fat diet.
      Coagulation time (CT) was observed by the glass method, and bleeding time (BT)
      was measured by tail-cutting method. The effects of CPFPI were also evaluated
      with prothrombin time (PT), activated partial thromboplastin time (APTT) and
      thrombin time (TT). HCT was measured by the electric tesistance method,
      hemorheology indicators were observed by auto-hemorheological instrument. The
      level of NO in blood serum was measured by NO assay kit. RESULT: CPFPI 65.40 mg x
      kg(-1) significantly prolonged CT, BT, PT, APTT and TT in rats. The viscosity of
      whole blood and plasma, hematocrit, erythrocyte aggregation and rigidity index,
      and reduced viscosity of whole blood in 65.40 mg x kg(-1) groups were lower than
      model group. CPFPI 65.40 mg x kg(-1) can raise the level of NO in blood serum.
      32.70 mg x kg(-1) markedly prolonged CT, PT and APTT and decreased whole blood
      viscosity, erythrocyte aggregation index and whole blood reduction viscosity.
      CONCLUSION: CPFPI has a significant effect in improving coagulability and
      hemorheology index and enhancing NO content in blood serum.

PMID- 22860465
TI  - [Intestinal absorption effect of Angelica dahurica extract on puerarin of
      puerariae Lobatae Radix].
AB  - OBJECTIVE: To study the effect of extractive Angelica dahutica on intestinal
      absorption of puerarin, the mechanism of the absorption enhancement of A.
      dahutica was investigated, providing a new thread of combinations of the Chinese
      herbal drugs. METHOD: Everted intestinal sac and in situ single pass perfusion
      were used to study the effect of gut absorption of puerarin solution containing
      the extractive A. dahurica as well as the influence of P-gp on the absorption of
      puerarin, and explore weather the extractive A. dahutica can enhance the
      absorption of puerarin and the mechanism of absorption of puerarin. RESULT: The
      puerarin could be absorbed at all of four intestinal segments with increaing
      absorption amount perunit as follows: ileum > colon > jejunum > duodenum. The
      absorption of puerarin in jejunum was significantly increased with the extractive
      A. dahutica in situ single pass perfusion of jejunum. The apparent permeability
      coefficient (Papp) and absorption rate constant (Ka) of puerarin in the jejunum
      were descreased gradually with higher concentrations, and the Papp with the Ka of
      jejunum solution containing the P-gp inhibitor of verapamil were increasing
      respectively 2.49, 2.60 (P < 0.001) than only the jejunum solution in absorption.
      The absorption of jejunum in pH 5.0, 6.8 were better than it in pH 7.4.
      CONCLUSION: The mechanism of absorption of jejunum was active absorption and was
      effected by P-gp. The extrative A. dahurica can enhance the absorption of the
      jejunum.

PMID- 22860466
TI  - [Effects of Forsythiae Fructus on guinea pig ileum contractility in vitro].
AB  - OBJECTIVE: To study contractility of guinea pig ileum in vitro,and analyze the
      mechanism of anti-emetic effects of Lianqiao. METHOD: Using emesis-relating
      agonists as drugs, the inhibitory effects of Lianqiao on guinea pig ileum
      contractility in vitro were observed in organ bath. RESULT: Lianqiao could
      inhibit guinea pig ileum spontaneous contractions, reducing the tone of
      contractions dose-dependently. Acetylcholine (Ach), histamine (His), 5
      hydroxytryptamine (5-HT) stimulated contractions of the guinea pig ileum,
      enhanced the tone and amplitude. All the three doses (10, 5, 2 g x L(-1)) of
      Lianqiao could suppress the contractility, significantly reduced the tone and
      amplitude of ileum contractions stimulated by drugs but not the frequency.
      Dopamine could inhibit the spontaneous contraction tone and amplitude of ileum;
      Both the large doses (10, 5 g x L(-1)) of Lianqiao could antagonise the
      inhibitory effect of DA, enhance the tone and amplitude. Small dose(2 g x L(-1))
      had additive effects on tone of ileum contractions with DA,but enhanced the
      amplitude not the frequency. CONCLUSION: Lianqiao have an inhibitory effect on
      guinea pig ileum contractions,the mechanism might be blocking M receptor, H1
      receptor, 5-HT receptor and D2 receptor or directly suppressed ileum smooth
      muscle. The mechanisms of anti-emetic effect of Lianqiao needs further study.

PMID- 22860467
TI  - [Study on intestinal absorption kinetics of syringopicroside in rats].
AB  - OBJECTIVE: To study the intestinal absorption mechanism of traditional Chinese
      medicine monomer syringopicroside in rats. METHOD: The in situ rat single-pass
      intestinal perfusion model was established to detect the concentration of
      syringopicroside by HPLC. The absorption at different intestine segments in rat
      and the influence of concentration, pH and P-glycoprotein inhibitors of the drug
      solution on the absorption of syringopicroside were also observed. RESULT: The
      absorption rate constant (K,) of syringopicroside at duodenum, jejunum, ileum,
      and colon were 0.00255, 0.00630, 0.00900, 0.00799 min- , respectively; Ka from
      intestine at syringopicroside concentration of 0.090, 0.180, 0.360 g x L(-1) were
      0.00370, 0.00708, 0.00694 min(-1), respectively; and Ka at pH of 7.4, 6.8 and 5.0
      were 0.00733, 0.00747, 0.00362 min(-1), respectively. P-glycoprotein inhibitor on
      the intestinal absorption of syringopicroside showed significant influence (P <
      0.05). CONCLUSION: Syringopicroside is well absorbed at the lower small
      intestine. When the drug concentration is low, the absorption rate constant is
      low, where as Ka increases at medium and high concentrations; the Ka is low at pH
      5.0 and increases at pH 6.8 and pH 7.4. Syringopicroside is proved to be a
      substrate of P-glycoprotein.

PMID- 22860468
TI  - [Study on in vitro microdialysis recovery of hydroxycamptothecine].
AB  - OBJECTIVE: To establish the mothod to dectect the microdialysis recovery of HCPT
      and to investigate the influencing factors, thus to supply experimental basis for
      in-vivo microdialysis of HCPT. METHOD: The in vitro recovery of HCPT was detected
      by concentration difference method (increment method and decrement method). The
      influence of flow rates, medium concentration and temperature on the HCPT
      recovery and the stability were studied. RESULT: The recovery detected by
      increment method was the same as by decrement method. The recovery was
      independent of HCPT concentrations in the medium. The hydroxycamptothecine
      recovery had good stability and increased as the temperature rose. CONCLUSION:
      Microdialysis sampling can be used for the pharmacokinetic study of HCPT.
      Retrodialysis can be used for the determination of the HCPT in vivo recovery.

PMID- 22860469
TI  - [Phaseoloideside E induces human hepatoma HepG2 cells apoptosis].
AB  - OBJECTIVE: To study in vitro anti-tumor activity of phaseoloideside E (PE) with
      human hepatoma HepG2 cells as the objective. METHOD: MTT assay was adopted to
      detect the cytotoxic effect of PE of different concentrations on HepG2 cells
      after being processed for 48 h. Changes in morphology of PE-processed cells were
      observed under an optical microscope and fluorescence microscope. DNA agrose gel
      electrophoresis was used to detect the DNA ladder, an important characteristic of
      cell apoptosis. The expression levels of Bax and Bcl-2 were determined by western
      blot assay. RESULT: PE dramatically repressed the viability of HepG2 cells.
      Typical morphological changes of apoptosis had been detected by both direct
      microscopic observation and Hoechst 33,258 staining. Typical DNA Ladder was also
      observed by agarose gel electrophoresis in the administration group, but it did
      not exist in the control group. Western blot showed that the expression of Bax
      was up-regulated and Bcl-2 was down-regulated. CONCLUSION: Above data
      demonstrates that PE can induce apoptosis in human hepatoma HepG2 cells, and
      indicate that PE-induced expression level changes of Bax and Bcl2 may be related
      to the apoptosis-induction effect.

PMID- 22860470
TI  - [Experimental study on effect of combination of Epimedii Folium/ Ligustri Lucidi
      Fructus and dexamethasone on asthmatic rats].
AB  - OBJECTIVE: To study the anti-inflammatory effect of the combination of Epimedii
      Folium, Ligustri Lucidi Fructus and dexamethasone on asthma and its effect in
      inhibiting adverse reaction against hormone. METHOD: Dexamethasone had been
      injected intraperitoneally into asthmatic model rats for 2 weeks, together with
      the oral administration of Epimedii Folium and Ligustri Lucidi Fructus. The
      contents of IL-4, INF-gamma, IL-5 and GCR in BALF, serum COR, plasma ACTH and
      hypothalamic CRH were observed. RESULT: The combination of Epimedii Folium,
      Ligustri Lucidi Fructus and dexamethasone can significantly decrease the contents
      of IL-5 and IL-4 in BALF and ACTH and CRH content in plasma, increase the content
      of IFN-gamma and GCR in BALF and balance Th1/Th2. CONCLUSION: The combination of
      Epimedii Folium, Ligustri Lucidi Fructus and dexamethasone has a better anti
      inflammatory effect on asthmatic model rats, and play a protective role in the
      pathway of endogenous dexamethasone.

PMID- 22860471
TI  - [Theoretical study on thirteen or fourteen incompatible medicaments and opposite
      drug properties of Tujia ethnic medical science].
AB  - Tujia ethnic medical science is an important sub-discipline of China's ethnic
      medicine system, which has rooted in major Tujia ethnic area such as Hunan,
      Hubei, Guizhou and Chongqing. It has its own theory, medication characteristic
      and experi-ence towards ethnic drugs. Particularly, in medication
      incompatibility, it has formed the principle of thirteen or fourteen incompatible
      medicament of traditional Tujia ethnic drugs, which play a certain role in
      guiding the usage and compatibility of tens of thousands of herbs. Focusing on
      the incompatibility that is abided by Tujia medical workers, the essay makes a
      textual study on the origin of herbs and conducts a preliminary study on the
      theoretical basis of thirteen or fourteen incompatible medicaments in terms of
      four properties of drugs and toxic and side-effect by reference to the records on
      nature and flavor and effectiveness, with a view of providing a preference to
      improve the incompatibility theory of traditional Chinese medicines and new ideas
      to further studies on the development and application of traditional ethnic
      drugs.

PMID- 22860472
TI  - [Restricting factors and countermeasures of Yunnan traditional Chinese medicine
      industry development].
AB  - This paper summarizes the current situation and restricting factors of the Yunnan
      traditional Chinese medicine industry. With further analysis comparing, the
      research puts forward some suggestions and strategic countermeasures to promote
      the development of the Yunnan traditional Chinese medicine industry.

PMID- 22860473
TI  - Advancing our nation's health: caring for our aging population.

PMID- 22860474
TI  - Responding to the silver tsunami with progressive and exciting educational
      initiatives.

PMID- 22860475
TI  - Quality care for older adults: the NLN Advancing Care Excellence for Seniors
      (ACES) project.
AB  - There is a significant need to improve the amount and quality of gerontological
      nursing content in pre-licensure nursing programs in the United States.The
      National League for Nursing's Advancing Care Excellence for Seniors (ACES)
      project is designed to enhance gerontological nursing content in all pre
      licensure nursing programs. Nurse educators can use the ACES framework to engage
      nursing students in studying the care of older adults through innovative and
      unique teaching/learning strategies, such as unfolding cases and simulation.The
      ACES framework, which includes the ACES Essential Knowledge Domains and Nursing
      Actions, is designed to enhance gerontological nursing content in pre-licensure
      nursing programs without adding additional content to curricula. Use of the ACES
      framework in pre-licensure nursing programs will help promote quality care of
      older adults in a variety of settings.

PMID- 22860476
TI  - Gerontological nursing content in general medical/surgical textbooks: where is
      it?
AB  - To provide quality care to the rapidly growing aging population, nursing
      education will need to be transformed. Although several approaches will be used
      to meet this challenge, fundamental to most nursing programs is the use of a
      general medical/surgical nursing textbook. This article examines the quantity and
      quality of gerontological nursing content found in five general medical/surgical
      nursing textbooks published between 2009 and 2011. The analysis shows that
      gerontological nursing content is poorly covered and of low quality. The findings
      point to the need to work with publishers to improve the quality and depth of
      content related to care of older adults in nursing textbooks.

PMID- 22860477
TI  - Developing positive attitudes toward geriatric nursing among Millennials and
      Generation Xers.
AB  - Despite the increase of the older adult population, there exists a shortage of
      health care professionals trained to help this population remain independent as
      long as possible. Ageism, common among younger adults, affects the capacity
      building of health care for older adults. Research has indicated that increased
      knowledge about older adults, as well as exposure to the elderly, may alter
      nursing students' attitudes regarding careers in gerontological nursing. However,
      questions remain as to what are the most effective ways to provide gerontological
      content in nursing programs and enhance attitudes toward older adults.With the
      understanding that younger adults see a need to balance work and play, a
      baccalaureate nursing program provides examples of ways to accomplish this
      through integration of courses, simulations, positive images of aging, and
      learning activities that enhance empathy for both frail and healthy older adults.

PMID- 22860478
TI  - Healthy ager: an interprofessional, service-learning, town-and-gown partnership.
AB  - Healthy Ager, an interprofessional service-learning clinical experience for
      health professions students, is a semester-long program of wellness and falls
      prevention for community-dwelling older adults. It provides a foundation for
      competency in geriatrics for students in nursing, physical therapy, social work,
      and communications disorders. Such interprofessional education is recommended by
      the Institute of Medicine.

PMID- 22860479
TI  - Early exposure to geriatric nursing through an externship program.
AB  - The Summer Geriatric Extern Program was developed in 2004 to provide nursing
      students between the junior and senior year an opportunity to learn more about
      careers in geriatric nursing.This full-time, eight-week commitment provides
      students with a stipend and a faculty mentor in their area of interest. Of the 24
      externs since the inception of the program, seven have enrolled in graduate
      programs. The findings suggest that the summer geriatric externship program is
      effective in developing interest in a geriatric nursing career and providing
      exposure to nursing research and other aspects of the faculty role.

PMID- 22860480
TI  - Promoting awareness of LGBT issues in aging in a baccalaureate nursing program.
AB  - It is estimated that up to 10 percent of the American population is lesbian, gay,
      bisexual, or transgender (LGBT) and that up to 7 million members of this
      population are elderly. Both the Institute of Medicine and Healthy People 2020
      have addressed the health disparities that affect elderly members of the LGBT
      community. Nurses are well positioned to bridge health disparities and provide
      culturally sensitive care across the lifespan, but compared with that of other
      disciplines, the nursing literature is lacking in content addressing LGBT health.
      Eliminating health disparities in the care of LGBT elders should be a priority in
      nursing education.The authors review the issues LGBT elders face and recommend
      how content related to LGBT aging can be integrated into nursing curricula.

PMID- 22860481
TI  - Geriatrics in simulation: role modeling and clinical judgment effect.
AB  - Clinical judgment development is critical to preparing students to safely meet
      the needs of an aging population. Evidence linking manikin-based simulation and
      clinical judgment is sparse.The purpose of this quasi-experimental international
      study was to determine the effect of expert role modeling on nursing students'
      clinical judgment in the care of a simulated geriatric hip fracture client.
      Students from five diverse schools (n = 275) participated in an unfolding
      simulation. Students were assigned to treatment or control groups.Treatment
      groups viewed an expert role model video.Trained observers rated student clinical
      judgment from selected video recordings using the Lasater Clinical Judgment
      Rubric (n = 94). Significant group differences (p = .000) were found for the
      clinical judgment dimensions of noticing, interpreting, and responding. Findings
      provide support for combining expert role modeling with clinical simulation to
      improve students' clinical judgment in the care of older adults.

PMID- 22860482
TI  - Attitudes of baccalaureate nursing students toward older adults: a pilot study.

PMID- 22860483
TI  - Integrating QSEN and ACES: an NLN Simulation Leader project.

PMID- 22860484
TI  - Attaining baccalaureate competencies for nursing care of older adults through
      curriculum innovation.
AB  - This new curriculum promotes up-to-date, evidence-based plans of care for older
      adults in acute care, long-term care, and community settings. Geriatric-specific
      content is a curricular thread and strong focus. Students have responded
      positively to the many opportunities they have to learn about the unique needs of
      older adults in multiple settings. Fortunately, we have several geriatric nurse
      practitioners on faculty along. Our students observe experts who are committed to
      promoting safe, quality, compassionate care to older adults in action on a daily
      basis.

PMID- 22860485
TI  - Engaging students in clinical reasoning when caring for older adults.

PMID- 22860486
TI  - Connecting undergraduate nursing students with older adults.

PMID- 22860487
TI  - Making global aging relevant to nursing students.

PMID- 22860488
TI  - Enhancing an academic-practice partnership with the creation of a geriatric nurse
      instructor position.

PMID- 22860489
TI  - Creative strategies for a stand-alone gerontology course for the nursing
      curriculum.

PMID- 22860490
TI  - The "Sensory Kit": teaching about sensory changes in older adults.

PMID- 22860491
TI  - Faculty Institute For Gerontological Nursing: a partnership for clinical
      education in long-term care.

PMID- 22860493
TI  - Preventive medicine in the 21st century -- a population challenge.

PMID- 22860492
TI  - Technology and gerontology: is this in your nursing curriculum?

PMID- 22860494
TI  - Prospective computerised surface wound mapping will optimise future body armour
      design.

PMID- 22860495
TI  - Optimising communication in the damage control resuscitation -- Damage Control
      Surgery sequence in major trauma management.
AB  - Damage Control Resuscitation and Damage Control Surgery (DCR-DCS) is an approach
      to managing severely injured patients according to their physiological needs, in
      order to optimise outcome. Key to delivering DCR-DCS is effective communication
      between members of the clinical team and in particular between the surgeon and
      anaesthetist, in order to sequence and prioritise interventions. Although the
      requirement for effective communication is self-evident, the principles to
      achieving this can be forgotten and sub-optimal when unexpected problems arise at
      critical points during management of challenging cases. A system is described
      which builds on the 'World Health Organisation (WHO) safer surgery checklist' and
      formalises certain stages of communication in order to assure the effective
      passage of key points. We have identified 3 distinct phases: (i) The Command
      Huddle, once the patient has been assessed in the Emergency room; (ii) The Snap
      Brief, once the patient has arrived in the Operating Room but before the start of
      surgery; and (iii) The Sit-Reps, every 10 minutes for the entire theatre team to
      maintain situational awareness and allow effective anticipation and planning.

PMID- 22860496
TI  - Non-operative management of liver trauma.
AB  - The liver is one of the commonest intra-abdominal organs injured worldwide in
      blunt and penetrating trauma and its management has evolved significantly in the
      last 30 years. Mandatory laparotomy has been replaced by an acceptance that for
      most blunt hepatic trauma, a selective non-operative approach is safe and
      effective with a failure rate ie the need to proceed to delayed laparotomy of
      approximately 10%. There is a markedly lower rate of complications in those that
      are managed non-operatively. Adjuncts to this conservative regimen such as
      angioembolisation and delayed laparoscopy to treat biliary peritonitis increase
      the chances of avoiding laparotomy. This belief in non-operative management has
      also been transferred to some degree to penetrating liver trauma, where there is
      a gradual accumulation of evidence to support this non-operative approach in a
      carefully selected group of patients. This article examines the evidence
      supporting the selective non-operative management of both blunt and penetrating
      liver trauma and describes the outcomes and complications.

PMID- 22860497
TI  - Outcomes from penetrating ballistic cervical injury.
AB  - AIMS: Ballistic cervical injury has become a significant source of both morbidity
      and mortality for the deployed UK soldier. The aim of this paper was to document
      a case series of ballistic cervical wounds to describe the pattern of these
      injuries and relate them to outcome. METHODS: The records of all UK service
      personnel sustaining wounds to the neck in Iraq or Afghanistan between 01 August
      2004 and 01 January 2008 were analysed following identification by the Joint
      Theatre Trauma Registry. Blunt or thermal injuries were excluded. RESULTS: The
      records of 75/76 service personnel sustaining penetrating cervical injury during
      this period were available for analysis. 56/75 (75%) were due to explosive
      fragmentation and the remainder due to gunshot wounds (GSW). 33/75 (44%) of
      soldiers sustained vascular injury, 32/75 (43%) injury to the spine or spinal
      cord, 29/75 (39%) injury to the larynx or trachea and 11/75 (15%) injury to the
      pharynx or oesophagus. 14/75 (19%) patients in this series underwent surgery in a
      hospital facility for treatment of potentially life threatening cervical
      injuries, with a survival rate after surgery of 12/14 (86%). The overall
      mortality from this series of battlefield penetrating neck injury was 63%.
      CONCLUSIONS: Penetrating cervical ballistic injury is a significant source of
      injury to deployed UK service personnel, predominantly due to neurovascular
      damage. Neck collars if worn would likely prevent many of the injuries in this
      case series but such protection is uncomfortable and may interfere with common
      military tasks. Newer methods of protecting the neck should be investigated that
      will be acceptable to the deployed UK soldier.

PMID- 22860498
TI  - Spinal fractures in current military deployments.
AB  - OBJECTIVE: To describe spinal fracture patterns presenting to deployed medical
      facilities during recent military operations. METHODS: Retrospective analysis of
      the United Kingdom Centre for Defence Imaging Computed Tomography database, 2005
      2009. Fractures are classified, mechanism noted and associated injuries recorded.
      Statistical analysis is by Fisher's Exact test. RESULTS: 128 fractures in 57
      casualties are analysed. Ballistic (79%) and non-ballistic mechanisms contribute
      to vertebral fracture at all regions of the spinal column in patients treated at
      deployed medical facilities. There is a high incidence of lumbar spine fractures,
      which are more likely to be due to explosion than gunshot wounding (p < 0.05).
      Two thirds of thoracolumbar spine fractures caused by explosive devices are
      unstable and are mainly burst-fractures in configuration. 60% of spinal fracture
      patients had concomitant injuries. There is a strong relationship between spinal
      fractures caused by explosions and lower limb fractures. CONCLUSION: Injuries to
      the spine caused by explosive devices account for greater numbers, greater
      associated morbidity and increasing complexity than other means of spinal injury
      managed in contemporary warfare. With the predominance of explosive injury in
      current conflict, this work provides the first detail of an evolving injury
      mechanism with implications for injury mitigation research.

PMID- 22860499
TI  - The Skeleton Coast Diet Plan: body mass and body fat changes on an arduous
      expedition.
AB  - OBJECTIVES: No one has ever walked the 500 Km Skeleton Coast of Namibia totally
      unsupported. Fourteen explorers overcame this by carrying, along with all their
      other equipment, hand-held pumps to desalinate sea water on a daily basis to
      produce sufficient potable water. This paper highlights the changes in body mass,
      waist circumference and body fat in the group on this unique 20 day expedition.
      METHODS: Eight males (mean (SD)) 42.3 (9.7) years, height 1.741 (0.043) m, weight
      78.7 (8.6) kg, body mass index (BMI) 24.8 (2.0) kg/m(2)) and six females (mean
      (SD) 40.0 (5.3) years, height 1.628 (0.043) m, weight 63.2 (5.5) kg, BMI 23.8
      (1.8) kg/m(2)) undertook the expedition. Average pack weight at the start of the
      expedition for the men was 32.5 kg, and 26.5 kg for the women. On most days, the
      team walked for 8 - 10 hours on varying terrain then pumped water for a further 4
      hours. Measurements taken included height, body mass, waist circumference and
      skin-fold thickness at four regions of the body, and were taken before, during
      and at the end of the expedition. The approximate daily calorific intake for each
      team member was 2400 - 3000 kcal. RESULTS: Significant decreases in mean body
      mass (p < 0.001, d=0.50) and mean BMI (p < 0.001, d = 0.67) were observed after
      the 20 day trek compared to baseline values. Mean waist circumference decreased
      during the expedition (p < 0.001, d = 0.67). There were significant reductions in
      all measures of skinfold thicknesses and overall percentage body fat at Day 13 (p
      < 0.001, d = 1.19) and Day 21 (p < 0.001, d = 1.98) in comparison to baseline
      values CONCLUSIONS: All participants lost significant amounts of both body mass
      and body fat, with body fat reducing by over 30%.

PMID- 22860500
TI  - Can adventurous training have a role in improving clinical outcomes?
AB  - The aim of military adventurous training (AT) is "to develop, through authorised
      challenging pursuits and within an outdoor environment, leadership and the
      qualities necessary to enhance the performance of military personnel during peace
      and war". An increasing amount of effort is being applied by all three services
      to increase participation in AT to achieve these, largely immeasurable, aims.
      Existing guidance to Commanding Officers dictates that, where possible, 20% of a
      unit strength should undertake some form of AT annually with 5% taking part in an
      overseas expedition. In a speech in 2008 Alan Johnson, the then Secretary of
      State for Health, acknowledged that for Armed Forces medical personnel 'just as
      important as clinical skills are issues such as leadership, communication,
      adaptability and teamwork." Controlled exposure to risk, discomfort and personal
      hardship is a common theme for both AT activities and military deployments. Both
      General Medical Council competencies for all doctors and the Royal College of
      Anaesthetists military module include elements which can effectively be taught
      and developed through training in an outdoors environment. These skills include
      communication skills, leadership, risk assessment and interdisciplinary working.
      In this review the value of AT in training doctors to develop those attributes is
      examined.

PMID- 22860501
TI  - Bullying and the UK Armed Forces.
AB  - There are certain characteristics of the culture and environment in the Armed
      Forces that may be conducive to bullying. In this article we examine the cultural
      and environmental factors that may encourage such behaviour and those that act as
      deterrents for victims to come forward. We will look at the scope of this problem
      within the UK Armed Forces specifically, before more generally considering the
      psychological impact of bullying. There appears to be an overall downward trend
      in bullying within the UK Armed Forces and a positive increase in complaints as
      more victims step forward. We conclude by highlighting some areas for further
      development.

PMID- 22860502
TI  - A comparison of performance between Teflon and polyurethane safety cannulae at
      extremes of operating temperatures.
AB  - OBJECTIVES: In the United Kingdom, approximately eight million peripheral
      cannulations are performed each year. Intravenous cannulae are made from either
      polytetrafluoroethylene (Teflon) or polyurethane. Polyurethane has a lower
      incidence of thrombophlebitis, however the physical characteristics of
      polyurethane may make the cannulae difficult to use at higher ambient
      temperatures. This effect maybe of importance to those involved in cannulation in
      extreme environments and especially for military doctors deployed in current
      theatres of operations. METHODS: In a randomised single blinded study we
      investigated the different characteristics of Teflon and polyurethane cannulae
      (Vasofix Safety Cannulae, B Braun) at three different temperatures (-10 degrees
      C, 21 degrees C and 40 degrees C). RESULTS: There is no statistically significant
      difference in the ease or speed of cannulation of either polyurethane or Teflon
      safety cannulae in extremes of temperature. CONCLUSIONS: This study provides
      evidence that performance of polyurethane safety cannulae are not impaired by
      temperature extremes.

PMID- 22860503
TI  - Falls from height: injury and mortality.
AB  - OBJECTIVES: To determine how Injury Severity Score (ISS) and mortality relate to
      height fallen, and to determine other predictors of mortality including intent
      and body region injured. METHODS: A pre-hospital retrospective, observational
      database study was conducted. Injured or deceased patients following a fall from
      height (FFH), aged 16 or over, attended to by London Helicopter Emergency Medical
      Services (HEMS), between Jan 2008 to July 2009 were included in the study. In
      addition to the database, HEMS mission 'run sheets' provided further information.
      RESULTS: 117 (91 males and 26 females) patients met the inclusion criteria. The
      mean age was 37 years (range 16 - 85). 34/117 (29%) died. The mean ISS was 28.6
      (median 17) and the mean height fallen 9.9m (3rd floor). In the group that died
      the mean height was 16.7m (5th floor). Height fallen was found to be a
      significant predictor of mortality (p < 0.001), as were injuries to the chest
      and/or head (p < 0.05). In patients with head and chest injuries, a 50% mortality
      rate was estimated to occur at falls from 10.5m, compared to 22.4m in those
      without injuries to head or chest. Deliberate falls were more common amongst
      females than males (chi-squared test, p = 0.001), were associated with greater
      ISS (Mann Whitney test, p < 0.001) and were more likely to result in death (chi
      squared test, p < 0.001). CONCLUSIONS: Height fallen correlates with ISS and is a
      significant predictor of death. Chest and/or head injuries significantly
      increased the likelihood of death following a FFH. This information may enhance
      triage criteria applied to tasking of emergency response vehicles, and strategies
      in injury prevention. Other potential predictors of mortality were not found to
      be significant.

PMID- 22860504
TI  - Management of a wild animal bite in a rabies enzootic area.
AB  - The British Armed Forces of the 21st century are trained and operate worldwide,
      often in places where rabies control is poor and prevalence may be high.
      Currently rabies is not a routine vaccination for all service personnel.
      Awareness of the risk of rabies, action to take post potential exposure, prompt
      access to clear management advice and reliable supplies of Rabies Immunoglobulin
      and Rabies Vaccination are critical. We describe the management of a recent case
      of animal bite in Kenya and discuss current recommendations.

PMID- 22860505
TI  - Successful surgical treatment of Q fever endocarditis with mitral valve repair.
AB  - We report a case of successful surgical treatment of Q fever endocarditis with
      mitral valve repair in a 66-year old retired British soldier. Valve replacement
      is invariably undertaken in Q fever endocarditis due to the degree of valvular
      damage and concerns about eradicating the organism, Coxiella burnetii. Our unique
      case allowed valve repair since pre-existing myxomatous degeneration and
      subsequent posterior mitral valve leaflet prolapse resulted in significant excess
      valve tissue, allowing quadrangular resection of the damaged and perforated P2
      portion of this leaflet. Follow-up at four years (including three years of
      antibiotic treatment) has confirmed excellent valve repair, with no
      echocardiographic, clinical or microbiological evidence of recurrence. We are
      only the second group to describe valve repair in a patient with chronic Q fever
      endocarditis. Valve repair is preferable to valve replacement for Q fever
      endocarditis, if technically possible.

PMID- 22860506
TI  - Self-assessment exercises in Emergency Radiology I -- abdominal trauma.
AB  - This is the first of three self-assessment articles which aim to further readers'
      understanding of diagnostic imaging and its integral role in the management of
      patients with emergency conditions, through a series of case studies.

PMID- 22860507
TI  - Obtaining multinational consensus on future combat face and neck protection --
      proceedings of the Revision Military Protection Workshop.

PMID- 22860508
TI  - Management of ocular trauma by maxillofacial surgeons at the Role 3, ISAF
      Hospital Kandahar over a 21 month period.

PMID- 22860509
TI  - Undifferentiated febrile illnesses amongst British troops in Helmand,
      Afghanistan.

PMID- 22860510
TI  - Children associate racial groups with wealth: evidence from South Africa.
AB  - Group-based social hierarchies exist in nearly every society, yet little is known
      about whether children understand that they exist. The present studies
      investigated whether 3- to 10-year-old children (N=84) in South Africa associate
      higher status racial groups with higher levels of wealth, one indicator of social
      status. Children matched higher value belongings with White people more often
      than with multiracial or Black people and with multiracial people more often than
      with Black people, thus showing sensitivity to the de facto racial hierarchy in
      their society. There were no age-related changes in children's tendency to
      associate racial groups with wealth differences. The implications of these
      results are discussed in light of the general tendency for people to legitimize
      and perpetuate the status quo.

PMID- 22860511
TI  - Biotin-beta-cyclodextrin: a new host-guest system for the immobilization of
      biomolecules.
AB  - The formation of stable supramolecular interactions between biotin and beta
      cyclodextrin was studied. An association constant of 3 * 10(2) M(-1) could be
      determined by NMR measurements by mapping the high field shift differences of the
      beta-cyclodextrin protons (H-3) at different biotin concentrations. With the aim
      to demonstrate a new alternative for the immobilization of bioreceptors, biotin
      and beta-cyclodextrin tagged biomolecules were immobilized on transducer
      surfaces, which were functionalized with the correspondent host-guest partner.
      The reliability of this new affinity system was investigated using two enzymes
      (glucose oxidase and polyphenol oxidase) as biomolecule models. This
      supramolecular inclusion complex shows clear advantages to the classic biotin
      (strept)avidin-biotin system due to a detrimental effect of the additional avidin
      layer reducing the transduction efficiency. A 7-fold increase in the maximum
      current density and an almost 20 times higher sensitivity were exhibited by the
      immobilized biological layer obtained using this new host-guest system.

PMID- 22860512
TI  - Electronic structure of an [FeFe] hydrogenase model complex in solution revealed
      by X-ray absorption spectroscopy using narrow-band emission detection.
AB  - High-resolution X-ray absorption spectroscopy with narrow-band X-ray emission
      detection, supported by density functional theory calculations (XAES-DFT), was
      used to study a model complex, ([Fe(2)(MU-adt)(CO)(4)(PMe(3))(2)] (1, adt = S
      CH(2)-(NCH(2)Ph)-CH(2)-S), of the [FeFe] hydrogenase active site. For 1 in powder
      material (1(powder)), in MeCN solution (1'), and in its three protonated states
      (1H, 1Hy, 1HHy; H denotes protonation at the adt-N and Hy protonation of the Fe
      Fe bond to form a bridging metal hydride), relations between the molecular
      structures and the electronic configurations were determined. EXAFS analysis and
      DFT geometry optimization suggested prevailing rotational isomers in MeCN, which
      were similar to the crystal structure or exhibited rotation of the (CO) ligands
      at Fe1 (1(CO), 1Hy(CO)) and in addition of the phenyl ring (1H(CO,Ph),
      1HHy(CO,Ph)), leading to an elongated solvent-exposed Fe-Fe bond. Isomer
      formation, adt-N protonation, and hydride binding caused spectral changes of core
      to-valence (pre-edge of the Fe K-shell absorption) and of valence-to-core
      (Kbeta(2,5) emission) electronic transitions, and of Kalpha RIXS data, which were
      quantitatively reproduced by DFT. The study reveals (1) the composition of
      molecular orbitals, for example, with dominant Fe-d character, showing variations
      in symmetry and apparent oxidation state at the two Fe ions and a drop in MO
      energies by ~1 eV upon each protonation step, (2) the HOMO-LUMO energy gaps, of
      ~2.3 eV for 1(powder) and ~2.0 eV for 1', and (3) the splitting between iron
      d(z(2)) and d(x(2)-y(2)) levels of ~0.5 eV for the nonhydride and ~0.9 eV for the
      hydride states. Good correlations of reduction potentials to LUMO energies and
      oxidation potentials to HOMO energies were obtained. Two routes of facilitated
      bridging hydride binding thereby are suggested, involving ligand rotation at Fe1
      for 1Hy(CO) or adt-N protonation for 1HHy(CO,Ph). XAES-DFT thus enables
      verification of the effects of ligand substitutions in solution for guided
      improvement of [FeFe] catalysts.

PMID- 22860513
TI  - Antimicrobial responses of primary gingival cells to Porphyromonas gingivalis.
AB  - BACKGROUND: Human beta-defensins (hBDs) and the C-C chemokine ligand 20 (CCL20)
      produced by gingival epithelial cells (GECs) and fibroblasts (HGFs) are
      antimicrobial peptides (AMPs) that play an important role in innate immunity. The
      aim of this study was to determine the differential immune response of GECs and
      HGFs to the oral commensal Streptococcus gordonii (SG) and the pathogen
      Porphyromonas gingivalis (PG). MATERIAL AND METHODS: In addition to the analysis
      of gingival biopsies, primary GECs and HGFs were exposed to SG and/or PG, and
      expression of various AMPs and pro-inflammatory mediators was studied by real
      time PCR and ELISA. RESULTS: Gene expression of AMPs was detected in gingival
      connective tissue. Both SG and PG induced the mRNA-expression of hBD-2 and hBD-3
      in GECs as well as HGFs after 24 h (p < 0.05). In HGFs, the commensal bacterium
      SG stimulated the mRNAs of hBD-3 and CCL20 after 24 h (p < 0.05), while not in
      GECs. In GECs, the inductive effect of PG on the mRNA-expression of hBD-2 was
      amplified when cells were first exposed to commensal SG (for 1 h) prior to
      stimulation with PG (SG-PG; p < 0.05). CONCLUSION: Our data indicate that cell
      bacteria interactions and/or bacteria-bacteria cross-talk may have an impact on
      AMP-regulation in gingiva.

PMID- 22860514
TI  - Redox-induced conformational switching in photosystem-II-inspired biomimetic
      peptides: a UV resonance Raman study.
AB  - Long-distance electron transfer (ET) plays a critical role in solar energy
      conversion, DNA synthesis, and mitochondrial respiration. Tyrosine (Y) side
      chains can function as intermediates in these reactions. The oxidized form of
      tyrosine deprotonates to form a neutral tyrosyl radical, Y(*), a powerful
      oxidant. In photosystem II (PSII) and ribonucleotide reductase, redox-active
      tyrosines are involved in the proton-coupled electron transfer (PCET) reactions,
      which are key in catalysis. In these proteins, redox-linked structural dynamics
      may play a role in controlling the radical's extraordinary oxidizing power. To
      define these dynamics in a structurally tractable system, we have constructed
      biomimetic peptide maquettes, which are inspired by PSII. UV resonance Raman
      studies were conducted of ET and PCET reactions in these beta-hairpins, which
      contain a single tyrosine residue. At pH 11, UV photolysis induces ET from the
      deprotonated phenolate side chain to solvent. At pH 8.5, interstrand proton
      transfer to a pi-stacked histidine accompanies the Y oxidation reaction. The UV
      resonance Raman difference spectrum, associated with Y oxidation, was obtained
      from the peptide maquettes in D(2)O buffers. The difference spectra exhibited
      bands at 1441 and 1472 cm(-1), which are assigned to the amide II' (CN) vibration
      of the beta-hairpin. This amide II' spectral change was attributed to substantial
      alterations in amide hydrogen bonding, which are coupled with the Y/Y(*) redox
      reaction and are reversible. These experiments show that ET and PCET reactions
      can create new minima in the protein conformational landscape. This work suggests
      that charge-coupled conformational changes can occur in complex proteins that
      contain redox-active tyrosines. These redox-linked dynamics could play an
      important role in control of PCET in biological oxygen evolution, respiration,
      and DNA synthesis.

PMID- 22860515
TI  - Syntheses and characterization of six quaternary uranium chalcogenides A2M4U6Q17
      (A = Rb or Cs; M = Pd or Pt; Q = S or Se).
AB  - The A(2)M(4)U(6)Q(17) compounds Rb(2)Pd(4)U(6)S(17), Rb(2)Pd(4)U(6)Se(17),
      Rb(2)Pt(4)U(6)Se(17), Cs(2)Pd(4)U(6)S(17), Cs(2)Pd(4)U(6)Se(17), and
      Cs(2)Pt(4)U(6)Se(17) were synthesized by the high-temperature solid-state
      reactions of U, M, and Q in a flux of ACl or Rb(2)S(3). These isostructural
      compounds crystallize in a new structure type, with two formula units in the
      tetragonal space group P4/mnc. This structure consists of a network of square
      planar MQ(4), monocapped trigonal-prismatic UQ(7), and square-antiprismatic UQ(8)
      polyhedra with A atoms in the voids. Rb(2)Pd(4)U(6)S(17) is a typical
      semiconductor, as deduced from electrical resistivity measurements. Magnetic
      susceptibility and specific heat measurements on single crystals of
      Rb(2)Pd(4)U(6)S(17) show a phase transition at 13 K, the result either of
      antiferromagnetic ordering or of a structural phase transition. Periodic spin
      polarized band structure calculations were performed on Rb(2)Pd(4)U(6)S(17) with
      the use of the first principles DFT program VASP. Magnetic calculations included
      spin-orbit coupling. With U f-f correlations taken into account within the GGA+U
      formalism in calculating partial densities of states, the compound is predicted
      to be a narrow-band semiconductor with the smallest indirect and direct band gaps
      being 0.79 and 0.91 eV, respectively.

PMID- 22860567
TI  - Dietary iron-initiated lipid oxidation and its inhibition by polyphenols in
      gastric conditions.
AB  - The gastric tract may be the first site where food is exposed to postprandial
      oxidative stress and antioxidant activity by plant micronutrients. After food
      intake, dietary iron, dioxygen, and emulsified lipids come into close contact and
      lipid oxidation may take place. This study investigated lipid oxidation and its
      inhibition by dietary polyphenols in gastric-like conditions. Lipid oxidation
      induced by heme and nonheme iron was studied in acidic sunflower oil-in-water
      emulsions. The emulsifier type (bovine serum albumin, phospholipids), pH, and
      iron form were found to be factors governing the oxidation rates. Quercetin,
      rutin, and chlorogenic acid highly inhibited the metmyoglobin-initiated lipid
      oxidation in both emulsified systems at pH 5.8. Additionally, quercetin inhibited
      nonheme iron-initiated processes, while it was inefficient with hematin as an
      initiator. The presence of human gastric juice did not influence lipid oxidation,
      although it diminished the antioxidant activity of phenolics. Model emulsions may
      thus be valuable tools to study the gastric stability of polyunsaturated lipids.

PMID- 22860568
TI  - Comprehensive two-dimensional gas chromatographic separations with a
      microfabricated thermal modulator.
AB  - Rapid, comprehensive two-dimensional gas chromatographic (GC * GC) separations by
      use of a microfabricated midpoint thermal modulator (MUTM) are demonstrated, and
      the effects of various MUTM design and operating parameters on performance are
      characterized. The two-stage MUTM chip consists of two interconnected spiral
      etched-Si microchannels (4.2 and 2.8 cm long) with a cross section of 250 * 140
      MUm(2), an anodically bonded Pyrex cap, and a cross-linked wall coating of
      poly(dimethylsiloxane) (PDMS). Integrated heaters provide rapid, sequential
      heating of each MUTM stage, while a proximate, underlying thermoelectric cooler
      provides continual cooling. The first-dimension column used for GC * GC
      separations was a 6 m long, 250 MUm i.d. capillary with a PDMS stationary phase,
      and the second-dimension column was a 0.5 m long, 100 MUm i.d. capillary with a
      poly(ethylene glycol) phase. Using sets of five to seven volatile test compounds
      (boiling point <=174  degrees C), the effects of the minimum (T(min)) and maximum
      (T(max)) modulation temperature, stage heating lag/offset (O(s)), modulation
      period (P(M)), and volumetric flow rate (F) on the quality of the separations
      were evaluated with respect to several performance metrics. Best results were
      obtained with a T(min) = -20  degrees C, T(max) = 210  degrees C, O(s) = 600 ms,
      P(M) = 6 s, and F = 0.9 mL/min. Replicate modulated peak areas and retention
      times were reproducible to <5%. A structured nine-component GC * GC chromatogram
      was produced, and a 21 component separation was achieved in <3 min. The potential
      for creating portable MUGC * MUGC systems is discussed.

PMID- 22860569
TI  - Burden of Alzheimer's disease-related mortality in the United States, 1999-2008.
AB  - OBJECTIVES: To update and examine Alzheimer's disease-related mortality trends
      according to age, sex, race and ethnicity, geography, and other case
      characteristics for a 10-year period. DESIGN: Trend and comparative analyses of
      the U.S. multiple-cause-of-death records for 1999 to 2008. SETTING: United
      States. PARTICIPANTS: Participants were decedents with Alzheimer's disease (AD)
      coded as underlying or associated cause of death; decedents with other forms of
      dementia or cognitive disorder were excluded. MEASUREMENTS: Case frequency, age
      specific death rates, and crude and age-adjusted mortality rates were estimated
      for all AD decedents from the sampled period. Measures of AD mortality burden
      were compared with those of other leading causes of death (e.g., diabetes
      mellitus, stroke). RESULTS: From 1999 to 2008, 879,281 AD-related deaths were
      identified. The age-adjusted mortality rate for AD increased from 45.3 per
      100,000 population (95% confidence interval (CI) = 45.0-45.7) in 1999 to 50.0 per
      100,000 population (95% CI = 49.7-50.3) in 2008. The average age at death was
      85.9. Differences in AD-related deaths varied according to sex, race and
      ethnicity, and geography. The number of AD-related deaths and age-specific
      mortality for persons aged 85 and older (n = 532,338, 1,096.6 per 100,000
      population) were comparable with those from the same age group who died from
      diabetes mellitus (n = 488,593, 1,006.5 per 100,000 population). CONCLUSION: The
      burden of AD-related mortality was substantial for the period 1999 to 2008. This
      burden is expected to grow rapidly as the baby boomer generation ages. Findings
      from this study may have important implications for present and future planning
      in medicine, social services, public policy, and public health.

PMID- 22860570
TI  - Voriconazole-induced photosensitivity: photobiological assessment of a case
      series of 12 patients.
AB  - BACKGROUND: Voriconazole, a broad-spectrum triazole antifungal agent increasingly
      used to treat aspergillosis, has been linked with acute photosensitivity and skin
      carcinogenesis. The action spectrum of the photosensitivity is unknown, while an
      indirect retinol effect secondary to the antifungal's impact on CYP450 enzymes
      has been proposed to contribute to the underlying mechanism. OBJECTIVES: To
      perform a detailed photobiological assessment of the photosensitivity presenting
      in a series of 12 patients treated with voriconazole. METHODS: Minimal erythemal
      dose thresholds (MED) to narrow wavebands of ultraviolet (UV) A, UVB and visible
      light were determined. Provocation testing was performed to broadband UVA (310
      400 nm) and to solar-simulated radiation (SSR) (290-400 nm). Patients underwent
      routine photopatch testing and laboratory investigations including serum vitamin
      A (retinol). RESULTS: Patients (eight men, four women; median age 54years, range
      40-63) experienced moderate-severe cutaneous erythema (n = 12), burning pain
      (n=5), itching (n=3), scaling (n=5), vesiculation (n=5) and oedema (n=1)
      following sunlight exposure; increased lentigines (n=4) and actinic cheilitis (n
      = 4) were also observed. While the majority (n=8) of patients showed normal MED
      thresholds to monochromator phototesting to UVB, UVA and visible light, a low MED
      to UVA was observed in four patients. Repeated provocation testing with broadband
      UVA and SSR provoked an abnormal erythema in eight and 10 patients, respectively.
      Serum retinol levels were mildly elevated in two patients but normal in the
      majority. CONCLUSION:  UVA sensitivity is the predominant finding in acute
      voriconazole-induced photosensitivity. We found little evidence of elevated
      circulating retinol as the causal factor. Patients with voriconazole-induced
      photosensitivity require education in appropriate UVA protective measures in
      addition to consideration of skin surveillance for malignant sequelae.

PMID- 22860571
TI  - High rate of antiretroviral drug resistance mutations in HIV type 1-infected
      Senegalese children in virological failure on first-line treatment according to
      the World Health Organization guidelines.
AB  - The rates of virological failure (VF) and HIV-1 drug resistance were evaluated in
      a cross-sectional study in HIV-1-infected children living in Dakar, and taking
      antiretroviral treatment (ART) according to WHO recommendations. The plasma HIV-1
      RNA load was measured using the Abbott m2000 RealTime HIV-1 assay. The full
      length protease gene and partial reverse transcriptase gene were sequenced, and
      resistance mutations were assessed by reference to the Stanford University HIV
      drug resistance database. Of 125 included children (median age, 7 years) taking
      first-line ART for a median duration of 20 months, 82 (66%) showed detectable HIV
      1 RNA load, and 70 (56%) met the 2010 revised WHO criteria of VF (defined as
      plasma HIV-1 RNA load >=3.7 log(10) copies/ml). Drug resistance results were
      available for 52 children with plasma HIV-1 RNA load >=3.0 log(10) copies/ml, and
      viruses carrying resistance mutations were found in 48 (92%) children. Among
      these 48, mutations conferring resistance to nucleoside reverse transcriptase
      inhibitors (NRTIs) or non-NRTIs (NNRTIs) were found in 42 (88%) and 47 (99%)
      children, respectively. The NRTI-resistant viruses harbored the M184V/I (95%),
      Q151M (2%), and thymidine-analogue mutations (40%), and the NNRTI-resistant
      viruses harbored the K103N (34%), Y181C (32%), G190A (23%), and K101E (21%)
      mutations. A high rate (56%) of VF was demonstrated in Senegalese children after
      20 months of first-line ART and therapeutic failure was assessed by the presence
      of antiretroviral drug resistance mutations in 9 out of 10 children in VF. These
      findings point out the difficulties of optimizing ART in children living in sub
      Saharan Africa, and the crucial need of laboratory monitoring reinforcement.

PMID- 22860572
TI  - Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: what is
      the optimal procedure for the surgical margins? A single center experience.
AB  - OBJECTIVES: To compare positive surgical margin rates after robot-assisted and
      pure laparoscopic radical prostatectomy when neurovascular bundles are preserved,
      and to identify parameters affecting surgical margin status. METHODS: From March
      2004 to January 2009, 279 consecutive prostatectomies with preservation of
      neurovascular bundles were carried out by the same surgeon: 175 robot-assisted
      radical prostatectomies and 104 laparoscopic radical prostatectomies. An
      intraperitoneal Montsouris's technique was used for all cases. Patient's age,
      body mass index, prostate weight, prostate-specific antigen level, clinical
      stage, preoperative and postoperative Gleason score, percentage of positive
      biopsies, pathological stage, and positive surgical margin status were
      prospectively recorded in an institutional database. The two groups were
      retrospectively analyzed and compared. RESULTS: Positive surgical margin rates
      were 17% and 13% for the robot-assisted radical prostatectomy and laparoscopic
      radical prostatectomy group (P = 0.4), respectively. At multivariable analysis,
      only prostate-specific antigen level and prostate weight significantly affected
      the surgical margin status, where the type of procedure (robotic vs laparoscopic)
      did not have any effect. CONCLUSION: In our single-surgeon experience, prostate
      specific antigen levels and prostate weight are predictive of positive surgical
      margin in patients undergoing nerve-sparing radical prostatectomy, whereas there
      seems to be no difference between the robot-assisted radical prostatectomy and
      the laparoscopic radical prostatectomy techniques.

PMID- 22860573
TI  - Pharmacokinetics and safety of single and multiple oral doses of meloxicam in
      adult horses.
AB  - BACKGROUND: Safety of meloxicam, a potent NSAID with selective COX-2 inhibition,
      has not been evaluated in horses. OBJECTIVES: To evaluate pharmacokinetics and
      safety of single and repeated oral doses of meloxicam in adult horses. ANIMALS:
      Forty-nine healthy, university-owned adult lightbreed horses. METHODS: Study
      conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose
      meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to
      5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6
      weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/kg PO q24h, n = 7) of
      meloxicam for 2 weeks, compared with control horses (placebo, n = 7, or
      phenylbutazone, 4.4 mg/kg q12h on day 1, 2.2 mg/kg q12h for 4 days, then 2.2
      mg/kg q24h for 9 days, n = 5). RESULTS: Maximum plasma concentration following a
      single oral dose of meloxicam was 915.1 +/- 116.9 ng/mL and elimination half-life
      10.2 +/- 3.0 hours. Meloxicam (0.6 mg/kg, q24h, PO for 6 weeks) yielded plasma
      concentrations between 100 and 1000 ng/mL and was well tolerated by healthy adult
      horses. Administration of 3-5 times the recommended dose of meloxicam was
      associated with decreased total serum protein and albumin concentrations,
      gastrointestinal damage, renal damage, or bone marrow dyscrasia. PBZ
      administration was associated with the development right dorsal colitis, gastric
      ulceration, and protein losing enteropathy in 2 horses. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Administration meloxicam at 0.6 mg/kg q24h was well tolerated for 6
      weeks, without drug accumulation in plasma. Higher doses were associated with
      dose-dependent adverse effects typical of class of drugs.

PMID- 22860574
TI  - Robust acenaphthoimidazolylidene palladium complexes: highly efficient catalysts
      for Suzuki-Miyaura couplings with sterically hindered substrates.
AB  - Robust acenaphthoimidazolylidene palladium complexes have been demonstrated as
      highly efficient and general catalysts for the sterically hindered Suzuki-Miyaura
      cross-coupling reactions in excellent yields even with low catalyst loadings
      under mild reaction conditions. The high catalytic activity of these complexes
      highlights that, besides the "flexible steric bulky" concept, sigma-donor
      properties of the NHC ligands are also crucial to accelerate the transformations.

PMID- 22860575
TI  - Standard pK(a) scales of carbon-centered indicator acids in ionic liquids: effect
      of media and structural implication.
AB  - Energetics of bond dissociation, especially the R-H bond heterolysis free energy
      (pK(a)), has played a central role in promoting chemistry to become a rational
      science. Despite the oceans of acidity studies in the literature, the current
      knowledge is limited to that in the classical molecular solvents and is unable to
      be extended to anticipate the acidity changes in ionic media. As the latter is
      now very popular for replacing volatile organic solvents, it becomes highly
      desirable to know how the driving force of bond cleavage is varied as the medium
      composition is switched from neutral molecules to the charged ions. Here we
      describe a general approach to measure absolute pK(a)'s in pure ionic liquid
      (IL). The standard conditions warranting accurate measurement were outlined. The
      pK(a)'s of the selected 18 C-H type indicator acids in four ILs were determined
      and a convenient indicator platform was constructed for easy expansion of acidity
      scales. These absolute pK(a)'s make possible, for the first time, direct
      comparisons of bond energies in IL with those in molecular solvent and in the gas
      phase and should be able to serve as the standard parameters for calibrating
      computational methods suitable for the studies in ionic media. The effect of
      cation and anion in IL in relation to structure was analyzed.

PMID- 22860576
TI  - Investigation on the antioxidant activity of leaves, peels, stems bark, and
      kernel of mango (Mangifera indica L.).
AB  - Bioactive polyphenols, cartenoids, and anthocyanins present in fruits and
      vegetables are receiving much attention because of their potential antioxidant
      activity. This study was conducted to determine antioxidant activity of leaves,
      peels, stem bark, and kernel of mango varieties langra and chonsa. Total phenolic
      (TPC) and total flavonoid contents (TFCs) in segments of langra ranged from 63.89
      to 116.80 mg GAE/g DW and 45.56 to 90.89 mg CE/g DW, respectively, and that of
      chonsa were 69.24 to 122.60 mg GAE/g DW and 48.43 to 92.55 mg CE/g DW,
      respectively. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and
      linoleic inhibition capacity in segments of langra ranged from 53.30% to 61.10%
      and 40.0% to 47.20%, respectively, whereas for chonsa; 56.40% to 66.0% and 48.1%
      to 49.0%, respectively. The reducing potentials of different segments of langra
      and chonsa at concentration of 10 mg/mL were 0.512 to 0.850 and 0.595 to 0.665
      mV, respectively. Comparison between both varieties showed chonsa exhibited
      better antioxidant activity. Data were analyzed by analysis of variance (ANOVA)
      using completely randomised design (CRD) under factorial.

PMID- 22860577
TI  - Iron-lactoferrin complex reduces iron-catalyzed off-flavor formation in powdered
      milk with added fish oil.
AB  - The iron-lactoferrin complex (FeLf) is useful for dietary iron supplementation.
      However, the effects of FeLf on iron-catalyzed off-flavors in lipid-containing
      food products have not been reported. In this study, we investigated the effects
      of FeLf on off-flavors development during the production and storage of powdered
      milk with added fish oil. Powdered milk samples were formulated with FeLf or iron
      (II) sulfate, then stored at 37  degrees C for 5 mo. A sensory evaluation
      revealed that FeLf delayed the development of oxidized flavor and reduced
      metallic taste in the powdered milk compared with iron (II) sulfate. Headspace
      gas chromatography-mass spectrometry analysis showed that oxidized volatile
      compounds, such as pentanal, hexanal, heptanal, octanal, 1-penten-3-one, (Z)-4
      heptenal, (E, E)-2,4-heptadienal, and (E)-2-octenal, were less developed in the
      powdered milk containing FeLf than in that containing iron (II) sulfate. Iron and
      lactoferrin (Lf) were retained in the high-molecular-weight (>10000 Da) fraction
      of the reconstituted FeLf-containing powdered milk after its manufacture and
      storage, whereas the antigenicity of Lf was lost after ultrahigh-temperature
      processing at 120  degrees C for 5 s. These results suggest that FeLf reduces the
      iron-catalyzed off-flavors that develop during the production and storage of
      powdered milk. The stable iron-holding property of FeLf contributes to the
      inhibition of oxidized and metallic volatile formation, although the loss of Lf
      antigenicity did not affect the stability of FeLf and the iron-catalyzed
      formation of off-flavors in the powdered milk. Consequently, FeLf is a suitable
      candidate for the simultaneous supplementation of a single food with iron and
      fish oil. PRACTICAL APPLICATION: The supplementation of food products with iron
      and fish oil is a useful approach to redressing their inadequate intake in many
      populations. The iron-lactoferrin complex can protect food products against the
      off-flavors caused by iron-catalyzed lipid oxidation. Our results show that the
      iron-lactoferrin complex is useful for the simultaneous fortification of foods
      and nutraceuticals with iron and fish oil because this complex also reduces the
      formation of iron-catalyzed off-flavors in powdered milk enriched with fish oil.

PMID- 22860578
TI  - Rapid determination of sugar level in snack products using infrared spectroscopy.
AB  - Real-time spectroscopic methods can provide a valuable window into food
      manufacturing to permit optimization of production rate, quality and safety.
      There is a need for cutting edge sensor technology directed at improving
      efficiency, throughput and reliability of critical processes. The aim of the
      research was to evaluate the feasibility of infrared systems combined with
      chemometric analysis to develop rapid methods for determination of sugars in
      cereal products. Samples were ground and spectra were collected using a mid
      infrared (MIR) spectrometer equipped with a triple-bounce ZnSe MIRacle attenuated
      total reflectance accessory or Fourier transform near infrared (NIR) system
      equipped with a diffuse reflection-integrating sphere. Sugar contents were
      determined using a reference HPLC method. Partial least squares regression (PLSR)
      was used to create cross-validated calibration models. The predictability of the
      models was evaluated on an independent set of samples and compared with reference
      techniques. MIR and NIR spectra showed characteristic absorption bands for
      sugars, and generated excellent PLSR models (sucrose: SEP < 1.7% and r > 0.96).
      Multivariate models accurately and precisely predicted sugar level in snacks
      allowing for rapid analysis. This simple technique allows for reliable prediction
      of quality parameters, and automation enabling food manufacturers for early
      corrective actions that will ultimately save time and money while establishing a
      uniform quality. PRACTICAL APPLICATION: The U.S. snack food industry generates
      billions of dollars in revenue each year and vibrational spectroscopic methods
      combined with pattern recognition analysis could permit optimization of
      production rate, quality, and safety of many food products. This research showed
      that infrared spectroscopy is a powerful technique for near real-time
      (approximately 1 min) assessment of sugar content in various cereal products.

PMID- 22860579
TI  - The effect of temperature on the color of red wines.
AB  - The effect of increased temperature on the color of red wines was studied due to
      its importance during storage and transport. The chemical reactions induced by
      elevated temperature were investigated by measuring the UV-VIS spectra. The
      temperature of the wines was increased from its common storage temperature (about
      14  degrees C) to higher temperatures (t= 20  degrees C, 25  degrees C, 30 
      degrees C, 35  degrees C, and 40  degrees C) and the UV/VIS spectra were recorded
      during several hours. The spectral changes obtained indicate the presence of
      quasi-first-order chemical processes justifying determination of the activation
      energies using their temperature dependence. The determined decay values
      (Villanyi Portugieser: E(VP) (a,420 nm) = 90.02 kJ/mol, E(VP) (a,520 nm) = 34.18
      kJ/mol, E(VP) (a,620 nm) = 54.55 kJ/mol; half-life values of 46.5 d [25  degrees
      C] and 9.5 d [35  degrees C] at 420 nm; 4.67 d [25  degrees C] and 2.0 d [35 
      degrees C] at 520 nm; 9.5 d [25  degrees C] and 2.4 d [35  degrees C] at 620 nm;
      Bikatory wine: E(Bk) (a,420 nm) = 82.07 kJ/mol and half-life values of 41.35 d
      [25  degrees C] and 4.001 d [35  degrees C] at 420 nm) of these reactions
      highlight a considerable change in the quality of wines stored for a few hours at
      elevated temperatures. Depending on polyphenol composition the wines show
      different half-life with regard to their color stability and browning reactions.
      Higher polyphenolic content helps to stabilize the wine against detrimental
      temperature effects. PRACTICAL APPLICATION: This research can be applicable to
      estimate the optimal temperature of red wines during storage and transport.

PMID- 22860580
TI  - Effects of pyruvate on lipid oxidation and ground beef color.
AB  - Our overall objective was to better understand the effects of added pyruvate on
      enhanced beef color stability. The 2 possible mechanisms assessed were the role
      of pyruvate in lipid oxidation and direct interaction between pyruvate and beef
      myoglobin. Microsomes were incubated with pyruvate at pH 5.6, 25  degrees C, and
      lipid oxidation was measured hourly for 3 h. Bovine oxymyoglobin at pH 5.6 was
      incubated with pyruvate and used to quantify both redox stability (metmyoglobin
      formation) and pyruvate-myoglobin adduction using mass spectrometry analysis.
      Surface color and lipid oxidation were measured on ground beef patties stored for
      6 d in polyvinyl chloride over-wrap (PVC) or high oxygen. Addition of pyruvate to
      microsomes decreased lipid oxidation compared with controls (P < 0.05).
      Conversely, no effect on myoglobin was observed (no changes in redox stability
      and no peaks corresponding to pyruvate were observed; P > 0.05). However,
      pyruvate increased color stability and decreased lipid oxidation of ground beef
      patties packaged in PVC and high oxygen. Pyruvate decreased nitric oxide
      metmyoglobin-reducing capacity and oxygen consumption of patties compared with
      controls (P < 0.05). This research suggests that pyruvate may improve beef color
      stability primarily through its antioxidant effect on lipids. PRACTICAL
      APPLICATION: Discoloration of meat often results in significant revenue loss.
      This study suggests that pyruvate can improve the color stability of patties
      packaged in high oxygen and PVC primarily through its antioxidant effect on
      lipids.

PMID- 22860581
TI  - Evaluation of antioxidant, radical scavenging activity and polyphenolics profile
      in Solanum torvum L. fruits.
AB  - Solanum torvum fruit widely used in traditional medicine of India and also in
      food preparation. Three different extracts such as water (WE), methanol (ME), and
      ethanol (EE) were used to evaluate their antioxidant and radical scavenging
      activity by different methods. All the assays results were compared with well
      known standard antioxidants. The IC(50) values of assays were determined. The
      total phenolic and flavonoids content were found to be maximum in water and
      ethanol extracts, respectively. The electron quenching ability of fruit extract
      was assayed by DPPH and reducing power assays succeeding order were ME > EE > WE,
      respectively. Inhibition of membrane damage, was assayed interns of oxidative
      hemolysis and lipid peroxidation assays, among all WE extract shows 58.00% and
      68.55 5% percentage of inhibition with 0.9 and 0.8 correlations (r(2)),
      respectively. Antioxidant and radical quenching efficiency were assayed by beta
      carotene bleaching and hydroxyl radical scavenging method and results were
      compared with vitamin C and catechin. The in vitro free radical quenching and
      antioxidant results were well correlated with in vitro DNA protection assay. As
      analyzed by HPTLC gallic acid content is high in WE (1394 +/- 25.0) and ME (598
      +/- 54.0) whereas ferulic acid is high in EE (32 +/- 5.94) MUg/g, respectively.
      This study indicate that S. torvum fruit is an excellent source of natural
      antioxidant and could be an effective nutritional food supplement, which interns
      will have therapeutic applications. PRACTICAL APPLICATION: In siddha medicine on
      the traditional systems of India the, ripened fruits are used in the preparation
      of tonic named as a "sundaivattaral choornam" is used to improve the health and
      prevent several diseases. This study has given an experimental evidence that S.
      torvum fruit is an excellent source of natural antioxidants.

PMID- 22860582
TI  - Fungal decay and shelf life of oranges coated with chitosan and bergamot, thyme,
      and tea tree essential oils.
AB  - Chitosan coatings, containing or not essential oils (bergamot, thyme and tea tree
      oil), were applied to oranges (cv. Navel Powell). Antifungal effect was evaluated
      by applying coatings before and after inoculating the fruit with Penicillium
      italicum CECT 2294 (10(5) spores/mL), preventive and curative treatments,
      respectively. The effect of coatings on the quality parameters (acidity, pH,
      soluble solids, juice percentage, weight loss, firmness, color parameters, and
      respiration rate) was controlled for the different oranges samples throughout the
      cold storage time. Preventive antimicrobial treatments with coatings containing
      tea tree oil were the most effective with a reduction of the microbial growth
      (expressed as the percentage of infected samples) of 50%, as compared to the
      uncoated samples. The coatings did not lead to any relevant changes in the
      development of the sample quality parameters throughout the cold storage, except
      for a slightly reduced loss of both weight and firmness when the coatings
      contained bergamot oil. PRACTICAL APPLICATIONS: Results of this study are a
      useful tool for the development of new environmental friendly and healthier
      commercial applications in the control of the main postharvest fungal decay of
      citrus fruits.

PMID- 22860583
TI  - Effect of high pressure and salt on pork meat quality and microstructure.
AB  - The interaction of salt (0%, 1.5%, and 3% in the final product) and a high
      pressure treatment (500 MPa, 20  degrees C, 6 min) was investigated using pork
      biceps femoris muscle. The Warner-Bratzler shear force and the water holding
      capacity (WHC) were assessed and linked to the microstructure evaluation by
      environmental scanning electronic microscopy (ESEM). Pressure-treated and cooked
      samples showed a high Warner-Bratzler shear force with a low WHC compared to
      control cooked samples. These negative effects could be linked to the general
      shrinkage of the structure as observed by ESEM. The addition of 1.5% salt was
      sufficient to improve the technological properties of the high-pressure-treated
      samples and to counteract the negative effect of high pressure on texture and
      WHC. This phenomenon could be linked to the breakdown in structure observed by
      ESEM. This study states that it is possible to produce pressurized pork products
      of good eating quality by adding limited salt levels.

PMID- 22860584
TI  - Effect of purified oat beta-glucan on fermentation of set-style yogurt mix.
AB  - Effect of oat beta-glucan on the fermentation of set-style yogurt was
      investigated by incorporating 0%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% of purified
      oat beta-glucan into the yogurt mix. It was found that levels up to 0.3% resulted
      in yogurts with quality characteristics similar to the control yogurt. Higher
      levels of beta-glucan however retarded the fermentation process with noticeable
      difference in the characteristics of the yogurt. Examination of the morphologies
      of yogurt with and without beta-glucan revealed that beta-glucan formed
      aggregates with casein micelle and did not form phase-separated domains. This
      research demonstrated that beta-glucan could be added to yogurt up to 0.3%, which
      meets the nutrient guidelines, to have added nutritional benefits. PRACTICAL
      APPLICATION: Yogurt is known for its beneficial effects on human health and
      nutrition. Yogurt production and consumption is increasing in the United States
      every year. However, it is lacking in beta-glucans, which are recognized for
      their nutritional importance as functional bioactive ingredients. The main
      objective was to develop and characterize low-fat yogurts with added beta-glucan.
      This research demonstrated that beta-glucan could be added to yogurt up to 0.3%,
      which meets the nutrient guidelines for added nutritional benefits, without
      affecting the characteristics of yogurt significantly. This study will benefit
      the dairy industry by generating new products offering healthy alternatives.

PMID- 22860585
TI  - Survival of Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella spp.
      on catfish fillets exposed to microwave heating in a continuous mode.
AB  - Microwave (MW) heating using continuous power output with feedback control and a
      modified ingredient formulation may provide better and consistent cooking of
      foods. Currently, household units with build-in inverter power supply units are
      available. These new generation MW ovens provide continuous, adjustable output
      and cooking, in contrast to the traditional rectifier-based ovens that rely on
      the on-off mechanism for control. This study attempted to apply a feedback power
      control (termed as modified or "smart" MW oven) and phosphate treatment to
      further improve heating uniformity and enhance food quality and safety. Listeria
      monocytogenes (Lm, 4-strain cocktail), Escherichia coli O157:H7 (Ec, 5-strain
      cocktail), and Salmonella spp. (Sal, 6-strain cocktail), surface inoculated onto
      catfish fillets (75 * 100 * 15 mm; weight 110 g), were heated using the modified
      MW oven to study the inactivation of the pathogens. The sensitivity of these 3
      bacteria to MW heating was in the order of Ec (most), Lm, and Sal (least).
      Greater than 4 to 5 log CFU reductions of Ec, Lm, or Sal counts on catfish fillet
      surfaces were inactivated within 2 min of 1250 W MW heating, where the fillet
      surface temperature increased from 10 to 20  degrees C to 80 to 90  degrees C. MW
      heating caused degradation of catfish fillet texture, which was noticeable as
      early as 10 to 15 s after the heating started, as evidenced by bumping sounds.
      Bumping can be significantly reduced by soaking fillets in phosphate solution.
      However, the results may need verification if applied in different MW ovens
      and/or with foods positioned away the geometric oven center. This study
      successfully demonstrated the feasibility of applying MW energy to eliminate
      foodborne pathogens on fish fillets. PRACTICAL APPLICATION: The results
      demonstrated in this report with the "smart" microwave oven design may enhance
      microwaveable food safety and quality, and therefore promote the microwaveable
      food business.

PMID- 22860586
TI  - Skin extracts from 2 Italian table grapes (Italia and Palieri) inhibit tissue
      factor expression by human blood mononuclear cells.
AB  - Grape and its products such as red wine and grape juice have well-known
      antithrombotic properties, which have been attributed to their high content in
      polyphenolic compounds. Most studies on the mechanisms underlying these
      beneficial effects, among which the suppression of tissue factor (TF) synthesis
      in blood mononuclear cells (MNC) and vascular endothelium is a prominent one,
      have been performed with purified polyphenols, while little is known about the
      effect of fresh grapes which contain a multitude of phytochemicals whose
      interaction may lead to different cell responses. In this study, we investigated
      the effect of grape skin extracts (GSEs) on TF expression in isolated blood MNC
      and in whole blood. Alcoholic extracts from skins of 2 grape varieties (Palieri
      and Italia) inhibited TF expression in lipopolysaccharide (LPS)-stimulated MNC in
      a concentration-dependent manner with >=90% inhibition of TF activity and antigen
      at 6 MUg/mL of gallic acid equivalents. Noteworthy, GSEs were also able to
      inhibit the appearance of TF in whole blood challenged with LPS. The 2 grape
      varieties displayed a fairly similar TF-inhibiting capacity despite marked
      differences in phenolic profile. When selected purified polyphenols were tested,
      their ability to inhibit TF expression was markedly lower as compared to grape
      extracts, whereas a mixture of some representative polyphenols was much more
      efficient, supporting the occurrence of a synergistic effect. Given the key role
      of cell TF in thrombotic diseases, the inhibition of MNC-mediated clotting
      activation, if confirmed by in vivo studies, might represent an important
      antithrombotic mechanism. PRACTICAL APPLICATION: Our data indicate that the
      combination of different polyphenols, as in grape extracts, is much more
      efficient than the single constituents, a finding that might be useful as
      starting point for the development of new antithrombotic nutraceutics. In
      addition, our study validated a simple, inexpensive, and physiologically relevant
      in vitro method on whole blood that allows the evaluation of one of the most
      important antithrombotic activities of food and food-derived products. The
      simplicity of the method makes it suitable also for screening purposes in large
      scale studies.

PMID- 22860587
TI  - Relation between chemical composition or antioxidant activity and
      antihypertensive activity for six essential oils.
AB  - Six essential oils (EOs), Juniperus phoenicea (leaves and berries), Thymus
      capitatus, Lauris nobilis, Melaleuca armillaris, and Eucalyptus gracilis, were
      screened for their antioxidant and antihypertensive activity as well as their
      chemical compositions. We identified and quantified 24 compounds (representing
      99.8% of total oil) for J. phoenicea leaves, 14 compounds (representing 98.8% of
      total oil) for J. phoenicea berries, 11 compounds (representing 99.6% of total
      oil) for T. capitatus, 32 compounds (representing 98.9% of total oil) for L.
      nobilis, 32 compounds (representing 98.7% of total oil) for M. armillaris, and 26
      compounds (representing 99.3% of total oil) for E. gracilis. In the 1,1-diphenyl
      2-picrylhydrazyl (DPPH) assay, the antioxidant activity was in the range of 0.59
      to 2183.6 mg/L, whereas T. capitatus (1.24 +/- 0.05 mg/L) gave the best activity
      in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate assay. Antihypertensive
      activity was evaluated by testing the vasorelaxing capacity of EOs on rat aorta
      precontracted by phenylephrine (10(-6)  M). T. capitatus and L. nobilis were most
      active for an antihypertensive activity (29 +/- 3 and 59 +/- 2 mg/L,
      respectively). Correlations between chemical composition or antioxidant activity
      and/or antihypertensive activity were studied. Significant correlation has been
      found for antihypertensive activity and p-cymene (R(2) = 0.86), beta-elemene
      (R(2) = 0.90), and beta-myrcene (R(2) = 0.76). A good correlation has been found
      between antihypertensive activity and antioxidant activity by DPPH assay (R(2) =
      0.98). Antioxidant activity can contribute to the prevention of the increase of
      the blood pressure. According to the literature, no study has been reported until
      now of correlation between antihypertensive activity and antioxidant activity.
      Natural EOs can find its interest and application in a medicinal area.

PMID- 22860590
TI  - Effect of high hydrostatic pressure on Aeromonas hydrophila AH 191 growth in
      milk.
AB  - Exposure to high pressure is an efficient method of bacterial inactivation that
      is particularly important for reducing the microbial load present in foods. In
      this study, we examined the high pressure inactivation of Aeromonas hydrophila AH
      191, a virulent strain that produces aerolysin, a cytotoxic, enterotoxic, and
      hemolytic toxin. High pressure treatment (250 MPa for 30 min at 25  degrees C in
      0.1 M PBS, pH 7.4) of A. hydrophila grown in milk reduced bacterial viability by
      at least 9 orders of magnitude. Under these conditions, the enterotoxic,
      hemolytic, and cytotoxic activities of A. hydrophila culture supernatants were
      unaltered. These results indicate the need for caution in the use of high
      pressure for food processing since although truly toxigenic bacteria may be
      inactivated, their toxins may not be, thus posing a risk to human health. At
      higher pressure (350 MPa) the inactivation of bacteria was much more effective.
      Scanning electron microscopy showed a significant decrease in the number of
      bacteria after higher pressurization (350 MPa for 1 h) and transmission electron
      microscopy showed irregular shaped bacteria, suggestive of important cell wall
      and membrane damage, and cytoplasm condensation. PRACTICAL APPLICATION: High
      pressure inactivates Aeromonas hydrophila efficiently but is enhanced when
      combined with moderate temperature (40  degrees C). The biological activities of
      toxins from this bacterium are unaltered under these conditions.

PMID- 22860591
TI  - Investigation on culturable microflora in Tibetan kefir grains from different
      areas of China.
AB  - Four samples of Tibetan kefir grains (TK-ZJUJ 01-04) from Tibet and surrounding
      areas were investigated via phenotypic and genotypic methods to compare and
      analyze the diversity of culturable microflora among different origins. As a
      result, 4 genera of microorganisms from TK-ZJUJ01: Bacillus subtilis (2.9 * 10(7)
      cfu/mL), Lactococcus lactis (8.2 * 10(7) cfu/mL), Kluyveromyces marxianus (3.0 *
      10(6) cfu/mL), Saccharomyces cerevisiae (9.0 * 10(6) cfu/mL); 4 genera from TK
      ZJUJ02: Lactobacillus kefiri (1.0 * 10(8) cfu/mL), Pichia kudriavzevii (5.0 *
      10(6) cfu/mL), K. marxianus (1.9 * 10(7) cfu/mL), Kazachstania unispora (6.2 *
      10(7) cfu/mL); 6 genera from TK-ZJUJ03: Leuconostoc lactis (4.6 * 10(7) cfu/mL),
      L. lactis (3.0 * 10(7) cfu/mL), Lactobacillus plantarum (3.0 * 10(7) cfu/mL), K.
      unispora (3.0 * 10(6) cfu/mL), K. marxianus (2.0 * 10(6) cfu/mL), (1.7 * 10(7)
      cfu/mL); and 4 genera from TK-ZJUJ04: L. plantarum (1.8 * 10(7) cfu/mL),
      Acetobacter fabarum (5.0 * 10(6) cfu/mL), K. unispora (6.2 * 10(7) cfu/mL),
      Pichia guilliermondii (6.2 * 10(7) cfu/mL) were identified. Yeasts like P.
      kudriavzevii and P. guilliermondii isolated in this study were the first time
      reported in Tibetan kefir grains. For TK-ZJUJ 01-03, lactic acid bacteria were
      the major microorganisms, which accounted for more than 50% of all the microbial
      population, while for TK-ZJUJ04, the largest microbial group was yeasts which
      accounted for more than 50%. In a word, study of diversity and composition of
      microflora provided us theoretical foundation for further investigation and
      application of Tibetan kefir grains. PRACTICAL APPLICATION: This is the basic
      research in order to develop and industrialize a new kind of yogurt starter which
      is naturally formed microbiota with both lactic acid bacteria and yeasts in it.

PMID- 22860592
TI  - Feasibility of coupling dehydration-impregnation by soaking treatment of meat
      with fermentation by Lactobacillus sakei.
AB  - This study examined the feasibility of coupling dehydration-impregnation by
      soaking (DIS) with a subsequent lactic fermentation in the treatment of meat. A
      series of beef fillets were subjected to 3 different DIS treatments. The
      resulting DIS-treated fillets had 3 different characteristics in terms of water
      activity, salt, and fermentable sugars contents. Fillets treated with the DIS
      with the shortest immersion time (5 h) and the highest salt concentration in the
      DIS bath (100 g/L) were inoculated with Lactobacillus sakei. A control group was
      left without inoculation. After 24 h incubation at 25  degrees C, only inoculated
      fillets showed signs of lactic fermentation. At 24 h, these fillets had a d
      lactic acid content of 68 MUmol/g dry basis and a high population of L. sakei
      revealed by methods of plate count and quantitative PCR. DIS could therefore be
      compatible with a subsequent fermentation step by L. sakei. PRACTICAL
      APPLICATION: Traditional meat preservation processes often combine unit
      operations such as salting, smoking, fermentation, and drying. In tropical
      countries, high temperatures and high relative humidity, poor infrastructure, and
      improper slaughterhouse practices explain the need for more drastic processes
      (more salt, more water loss) for meat preservation. Dehydration-impregnation by
      soaking (DIS) could be used as a rapid pretreatment of meat, in order to
      counteract tropical conditions. This study validates a novel approach whereby DIS
      is coupled with lactic fermentation by surface inoculation with Lactobacillus
      sakei. With a final drying step this process could be used for the treatment of
      whole meat pieces.

PMID- 22860593
TI  - Antifungal effect of Mexican oregano (Lippia berlandieri Schauer) essential oil
      on a wheat flour-based medium.
AB  - The antimicrobial activity of oregano has been attributed mainly to the presence
      of volatile compounds found in its essential oil (EO), mainly carvacrol and
      thymol. The search for antimicrobial activity of oregano EO with different
      concentrations of thymol and carvacrol, can lead to products with a wider range
      of applications. The aim of this work was to describe the in vitro antifungal
      effect of Mexican oregano (Lippia berlandieri Schauer) EO fractions on the growth
      of Aspergillus, Penicillium, and Rhizopus sp. The Mexican oregano EO fractions
      studied had different concentrations of carvacrol, which decreased from fraction
      1 to 5 (81% to 23%), while thymol content increased from 3% to 64%. Fungal
      inhibition was evaluated on a wheat flour-based medium with EO fractions
      concentrations ranging from 50 to 200 mg/kg. Radial growth curves were fitted
      using the modified Gompertz model (R(2)(adj) = 0.989 +/- 0.01). No significant
      differences (P > 0.05) were found with the different composition of the Mexican
      oregano EO fractions; nevertheless, fraction concentration presented significant
      (P < 0.05) mold inhibition as concentration increased. Rhizopus sp. (Rh18) showed
      a linear reduction on specific growth rate, on the maximum mold growth at the
      stationary phase, and an increase in the lag time as the concentration of the
      oregano EO increased; mold growth inhibition were achieved at 150 mg/kg in
      fractions 1 to 4, and at 100 mg/kg for fraction 5. Aspergillus sp. (As6) and
      Penicillium sp. (Pe36) were inhibited at 150 and 200 mg/kg, respectively. Results
      obtained suggest that Mexican oregano EO (Lippia berlandieri Schauer) compounds
      could be used as antimicrobial agents to prevent fungal growth in bakery
      products.

PMID- 22860594
TI  - The influences of natural zeolite (cliptinolite) on ammonia and biogenic amine
      formation by foodborne pathogen.
AB  - The influence of natural zeolite on biogenic amines (BAs) and ammonia (AMN)
      production by eight common gram negative and positive foodborne pathogens (FBP)
      were investigated in histidine decarboxylase broth (HDB). Presence of 1% zeolite
      in the HDB resulted in significantly higher AMN production. Histamine (HIS)
      production by gram positive bacteria was as low as 0.5 mg/L, whereas Escherichia
      coli produced 18.96 mg/L of HIS. The use of zeolite also significantly suppressed
      HIS accumulation by E. coli, Pseudomonas aeruginosa, S. paratyphi A (P < 0.05),
      although zeolite addition stimulated HIS production by K. pneumonia and Aeromonas
      hydrophila. The range of tyramine (TYR) production by gram positive bacteria was
      1.19 and 4.06 mg/L for Enteroccus faecalis and Listeria monocytogenes
      respectively. The results of study showed that the effect of zeolite on BAs and
      AMN production was dependent on bacterial strains, as well as zeolite
      concentrations used. PRACTICAL APPLICATION: Natural zeolites are the main
      absorptive, low-cost material used in agriculture and industry. Although the
      effect of zeolite on ammonia formation in some industrial systems is well known,
      there is limited information regarding the impact of zeolite on biogenic amine
      (BA) production by foodborne pathogens. The data presented in this article will
      help us to understand the impact of natural zeolite on BA and ammonia production
      by eight common foodborne pathogens.

PMID- 22860595
TI  - Fermentation by amylolytic lactic acid bacteria and consequences for starch
      digestibility of plantain, breadfruit, and sweet potato flours.
AB  - The potential of tropical starchy plants such as plantain (Musa paradisiaca),
      breadfruit (Artocarpus communis), and sweet potato (Ipomoea batatas) for the
      development of new fermented foods was investigated by exploiting the capacity of
      some lactic acid bacteria to hydrolyze starch. The amylolytic lactic acid
      bacteria (ALAB) Lactobacillus plantarum A6 and Lactobacillus fermentum Ogi E1
      were able to change the consistency of thick sticky gelatinized slurries of these
      starchy fruits and tubers into semiliquid to liquid products. Consequently, a
      decrease in apparent viscosity and an increase in Bostwick flow were observed.
      These changes and the production of maltooligosaccharides confirmed starch
      hydrolysis. Sucrose in sweet potato was not fermented by strain A6 and poorly
      fermented by strain Ogi E1, suggesting possible inhibition of sucrose
      fermentation. In all 3 starchy plants, rapidly digestible starch (RDS) was higher
      than slowly digestible starch (SDS) and resistant starch (RS) represented between
      17% and 30% dry matter (DM). The digestibility of plantain was not affected by
      fermentation, whereas the RDS content of breadfruit and sweet potato decreased
      and the RS content increased after fermentation. PRACTICAL APPLICATION: The
      characteristics resulting from different combinations of gluten free starchy
      plants (plantain, breadfruit, sweet potato) and amylolytic lactic acid bacteria
      (ALAB) offer opportunities to develop new functional fermented beverages, mainly
      for breadfruit and sweet potato, after further investigation of their
      formulation, sensory attributes, nutritional, and prebiotic characteristics.

PMID- 22860596
TI  - Effect of thyme oil on the preservation of vacuum-packaged chicken liver.
AB  - In this study fresh chicken liver meat was stored under vacuum packaging (VP) and
      under refrigeration (4  degrees C). The following treatments were used: V
      (control samples, stored under VP), VT1 (thyme oil; 0.1% v/w, stored under VP)
      and VT2 (thyme oil; 0.3% v/w, stored under VP). Lipid oxidation was low, as
      judged by determination of malondialdehyde (MDA) values, in vacuum-packaged
      chicken liver meat, both in the absence or presence of thyme essential oil (EO)
      during the entire storage period. Of the color parameters (L*, a*, b*) monitored
      during storage time, L* (lightness) values for vacuum-packaged chicken liver,
      irrespective of treatment, showed a varying trend, whereas a* (redness) values
      for V, VT1, and VT2 liver samples decreased, showing no significant differences.
      As determined by sensory analysis the observed shelf life of chicken liver
      samples was longest for VT2 (>12 d) followed by VT1 (12 d) and control (V)
      samples (7 d). Our results suggest that a Brochothrix thermosphact count (7 log
      CFU/g) and appearance of visible colonies can be used as indicators of chicken
      liver spoilage.

PMID- 22860597
TI  - Detection and isolation of low levels of E. coli O157:H7 in cilantro by real-time
      PCR, immunomagnetic separation, and cultural methods with and without an acid
      treatment.
AB  - Leafy greens such as cilantro, contaminated with Escherichia coli O157:H7, have
      been implicated in cases of human illnesses. High levels of microflora in fresh
      cilantro make recovery of low numbers of E. coli O157:H7 difficult. To improve
      upon current methods, immunomagnetic separation (IMS) techniques in combination
      with real-time PCR (RTiPCR) and selective enrichment protocols were examined.
      Rinsates were prepared from cilantro samples inoculated with low (~0.02 CFU/g)
      and slightly higher (~0.05 CFU/g) levels of E. coli O157:H7. Rinsate portions
      were enriched in modified buffered peptone water with pyruvate (mBPWp) for 5 h at
      37  degrees C. After 5 h, selective agents were added to samples and further
      incubated at 42  degrees C overnight. Detection and recovery were attempted at 5
      and 24 h with and without IMS. IMS beads were screened by RTiPCR for simultaneous
      detection of stx1, stx2, and uidA SNP. Additionally, broth cultures and IMS beads
      were streaked onto selective agar plates (Rainbow((r)) agar, R&F((r)) E. coli
      O157 Chromogenic medium, TC-SMAC and CHROMagarTM 0157) for isolation of E. coli
      O157:H7. Both broth cultures and IMS beads were also acid treated in Trypticase
      Soy Broth pH 2 prior to plating to selective media to improve upon cultural
      recovery. Although E. coli O157 strains were detected in most samples by PCR
      after 5 h enrichment, cultural recovery was poor. However, after 24 h enrichment,
      both PCR and cultural recovery were improved. Acidification of the broths and the
      IMS beads prior to plating greatly improved recovery from 24 h enrichment broths
      by suppressing the growth of competing microorganisms. PRACTICAL APPLICATION:
      Detection and recovery of Escherichia coli O157:H7 in fresh produce matrices
      (e.g., cilantro) can be complicated by high background microflora present in
      these foods. Rapid detection by molecular methods combined with effective
      enrichment and isolation procedures such as using immunomagnetic separation (IMS)
      techniques can quickly identify potential hazards to public health. Additional
      techniques such as acidification of enrichment broths can exploit acid resistance
      characteristics of pathogens such as E. coli O157:H7, facilitating their
      isolation in complex food matrices.

PMID- 22860598
TI  - Influence of yeast mannoproteins in the aroma improvement of white wines.
AB  - In the present work, 3 different yeast strains (1, 2, and 3) were used to
      elaborate white wines using Albarino must. The concentration of polymeric mannose
      was determined using a method based on the mannoprotein precipitation, hydrolysis
      and analysis of sylylated mannose derivatives by gas chromatography. Wines
      elaborated with the strain 1 (W1) presented a higher mannoprotein concentration
      than the other wines. The analysis of the volatile composition of wines showed
      significant differences (P < 0.05) among them, being W1 which presented the
      highest concentration of aroma compounds, mainly terpens and norisoprenoids. The
      sensorial analysis of wines also showed that W1 had the best quality. The results
      obtained from this work demonstrate that mannoproteins could be involved in the
      behavior observed. Some evidences were obtained using a model wine, where 2 major
      terpens in W1 were preferentially retained by the colloids rich in mannoproteins
      released by strain 1. PRACTICAL APPLICATION: White wines elaborated with yeast
      strains overproducing mannoproteins could have better quality than others.
      Mannoproteins could contribute to aroma enhancement of Albarino white wines.

PMID- 22860599
TI  - Baccharin prevents genotoxic effects induced by methyl methanesulfonate and
      hydrogen peroxide in V79 cells.
AB  - Baccharin is one of the major chemical compounds isolated from the aerial parts
      of Baccharis dracunculifolia DC (Asteraceae), a native plant of South America and
      the most important botanical source of the Brazilian green propolis that has been
      used in alternative medicine to treat inflammation, liver disorders, and stomach
      ulcers. The present study was carried out in V79 cells to determine the possible
      genotoxic and antigenotoxic activities of baccharin utilizing comet and
      micronucleus assays, where 2 known mutagenic agents with different mechanisms of
      DNA damage were used as positive controls. The V79 cells were treated with
      concentrations of baccharin (0.25, 0.5, 1.0, and 2.0 MUg/mL) and for to
      investigate the antigenotoxicity these concentrations were associated with methyl
      methanesulfonate (MMS; 200 MUM-comet assay and 400 MUM-micronucleus assay) or
      hydrogen peroxide (H(2)O(2;) 50 MUM-comet assay and 100 MUM-micronucleus assay).
      Statistically significant differences in the rate of DNA damage were observed in
      cultures treated with the highest concentration of baccharin when compared to the
      control group, but this difference was not found in the micronucleus assay. The
      results also showed that the frequencies of DNA damage and micronuclei induced by
      MMS and H(2)O(2) were significantly reduced after treatment with baccharin. The
      baccharin showed a chemoprevention effect and can be the chemical compound
      responsible for the antigenotoxicity also demonstrated by the B. dracunculifolia.
      The antioxidant potential of baccharin may be related to its chemoprevention
      activity induced against both genomic and chromosomal damages.

PMID- 22860600
TI  - Determination of the metals by ICP-MS in wild mushrooms from Yunnan, China.
AB  - The elemental contents of Li, Cs, U, Co, As, Sr, Cd, Ba, Pb, Sb in 157 wild-grown
      mushrooms were determined by inductively coupled plasma mass spectrometry (ICP
      MS). The mushrooms including 9 species were collected from 5 counties in Yunnan
      province, China. Based on the findings for the results from the certified
      reference materials GBW10014 (cabbage) and GBW10016 (tea), the data from the
      sample mushrooms were corrected. The contents of investigated trace elements in
      mushroom samples were determined as MUg/g dry weight (dw) in the range of 0.030
      to 13 for Li, 0.070 to 8.1 for Cs, 0.0010 to 0.28 for U, 0.040 to 5.4 for Co,
      0.070 to 44 for As, 0.28 to 86 for Sr, and 0.15 to 23 for Cd. The maximum
      contents were 58, 11, and 0.11 for Ba, Pb, and Sb, respectively. The minimum
      contents of Ba, Pb, and Sb were below the detection limit of the method used.
      PRACTICAL APPLICATION: The analysis of 9 species wild-grown edible mushrooms in
      different regions provides the useful information to evaluate the levels of
      elements or of the toxic heavy metals, such as Cd, As in wild-grown edible
      mushrooms which grew in different regions of China for consumers and other
      interested groups, especially for the regulators.

PMID- 22860602
TI  - Scientific relevance and the top eleven for 2011.

PMID- 22860601
TI  - Trans fatty acid contents in selected dietary fats in the Estonian market.
AB  - In response to public concern, this study assessed the fatty acid (FA)
      composition of blended spreads, margarines and shortenings in the Estonian retail
      market in 2011. Special attention was paid to the trans fatty acids (TFA)
      composition. The changes in these characteristics of selected dietary fats in the
      market over recent years are also presented. Twenty-six edible fat brands,
      available in the Estonian retail market in 2011, were purchased and FA
      compositions were analyzed by chromatography. Saturated fatty acids (SFA) were
      the dominant group of FAs for all blended spreads (49.6 to 65.8%), and for the
      majority of shortenings (from 21.1 to 54.6%). Cis monounsaturated fatty acids
      (MUFA) were the dominant group of FAs for the majority of margarines, ranging
      from 25.3% to 50.5%. The total TFA for blended spreads varied from 1.18% to
      9.08%, for margarines from 0.04% to 34.96% and for shortenings from 0.14% to
      39.50%. Octadecenoic (C18:1) isomers were the main TFA found. Compared to
      2008/2009, the industrially produced TFA (IP-TFA) content in several of the
      dietary fat brands was much reduced in 2011. This voluntary reformulation was
      probably a response to consumer demand associated with a public health campaign
      directed against IP-TFA in Estonian foods, and were mainly achieved by replacing
      TFA with SFA C12:0-C16:0. PRACTICAL APPLICATION: Present paper is directed toward
      public health related institutions and food industries producing foods with
      potentially high contents of trans fatty acids (TFA). According to the public
      concern TFA content in domestic blended spreads has declined significantly over
      the past 3 y in Estonia. The reduction in the TFA content was achieved by
      replacing TFA with saturated fatty acids (SFA) (C12:0-C16:0). To shift food
      composition toward healthier product formulations, mandatory labeling of the sum
      of IP-TFA and SFA (C12:0-C16:0) was recommended.

PMID- 22860603
TI  - The frontal lobe and thalamus have different sensitivities to hypoxia-hypotension
      after traumatic brain injury: a microdialysis study in rats.
AB  - After traumatic brain injury (TBI), lesions are anatomically heterogeneous, but
      the spatial heterogeneity of the post-traumatic brain's vulnerability to hypoxia
      hypotension (HH) has been poorly studied. Our objective was to compare the effect
      of HH after TBI on brain energy metabolism into two regions: the frontal lobe and
      the thalamus. Twenty-eight Sprague-Dawley rats were randomized into four groups:
      sham, TBI (brain trauma alone, impact acceleration, 450-g weight drop from 1.8
      m), HH (blood depletion to mean arterial pressure 40 mm Hg, FiO(2) 10%, 15 min),
      and TBI-HH (TBI followed by HH, 45-min delay). Cerebral perfusion pressure (CPP)
      was continuously measured. Brain microdialysis and brain tissue oxygen partial
      pressure (PtiO(2)) probes were both inserted stereotaxically into the right
      thalamus and frontal lobe. Except during the HH period, CPP was always above 60
      mm Hg. During the hour following the HH period, significant increases in cerebral
      lactate-pyruvate ratio, glycerol, and glutamate were observed, and were always
      higher in the frontal lobe than in the thalamus (p<0.001). In the TBI-HH group
      and in the frontal lobe, increases in glutamate and glycerol were significantly
      higher than in the HH group (p<0.001). During the 30 min following the HH phase
      (reperfusion), an increase in PtiO(2) was observed. In the TBI-HH group, this
      increase was significantly lower in the frontal lobe than in the thalamus. These
      findings demonstrate that in the early post-traumatic period, the metabolic
      cerebral response to HH is higher in the frontal lobe than in the thalamus, and
      is worsened by TBI, suggesting a higher vulnerability for the frontal lobes.

PMID- 22860606
TI  - The prognostic significance of traumatic brainstem injury detected on T2-weighted
      MRI.
AB  - OBJECT: Magnetic resonance imaging is frequently used to evaluate patients with
      traumatic brain injury in the acute and subacute setting, and it can detect
      injuries to the brainstem, which are often associated with poor outcomes. This
      study was undertaken to determine which MRI and clinical factors provide
      prognostic information in patients with traumatic brainstem injuries. METHODS:
      The authors performed a retrospective analysis of cases involving patients
      admitted to a Level I trauma center who were identified in a prospective database
      as having suffered traumatic brainstem injury identified on MRI. Patient outcomes
      were dichotomized to dead/vegetative versus functional groups. Standard
      demographic data, admission Glasgow Coma Scale (GCS) scores, results of the motor
      component of the GCS examination at admission and 24 hours later, CT scan
      findings, and peak intracranial pressure were collected from medical records.
      Volumetric analysis of each patient's injuries was performed with T2-weighted and
      gradient echo sequences. The T2-weighted MRI sequence for each patient was
      reviewed to determine the anatomical location of injury within the brainstem and
      whether the injury crossed the midline. RESULTS: Thirty-six patients who met the
      study inclusion criteria were identified. At 6-month follow-up, 53% of these
      patients had poor outcomes and 47% had recovered. Patients with injuries to the
      medulla or deep bilateral injuries to the pons did not recover. The T2 volumes
      were found superior to gradient echo sequences in regard to predicting survival
      (ROC/AUC 0.67, p = 0.07 vs 0.60, p = 0.29, respectively), but neither reached
      statistical significance. The timing of MR image acquisition did not influence
      the findings. The time from admission to MRI did not differ significantly between
      the recovered group and the poor-outcome group (p = 0.52, Mann-Whitney test), and
      lesion size as measured by T2 volume did not vary with time to scan (R(2) = 0.03,
      p = 0.3, linear regression). Performing a stepwise logistic regression with all
      the variables yielded the following factors related to recovery: crossing
      midline, p = 0.0156, OR 0.075; and 24-hour GCS motor score, p = 0.0045, OR =
      2.25, c-statistic 0.913. Further examination of these 2 factors disclosed the
      following: none of 15 patients with midline-crossing lesions and a 24-hour GCS
      motor score of 4 or less recovered; conversely, 12 of 13 patients with lesions
      that did not cross midline recovered, regardless of GCS motor score. CONCLUSIONS:
      Bilateral injury to the pons and medulla as detected on T2-weighted MRI sequences
      was associated with poor outcome in patients with brainstem injuries; T2 volumes
      were found superior to gradient echo sequences in regard to predicting survival,
      but neither reached statistical significance. When MRI findings were coupled with
      clinical examination findings, a strong correlation existed between poor outcome
      and the combination of bilateral brainstem injury and a motor GCS score of 4 or
      less 24 hours after admission.

PMID- 22860605
TI  - Comparative peptidomics analysis of neural adaptations in rats repeatedly exposed
      to amphetamine.
AB  - Repeated exposure to amphetamine (AMPH) induces long-lasting behavioral changes,
      referred to as sensitization, that are accompanied by various neuroadaptations in
      the brain. To investigate the chemical changes that occur during behavioral
      sensitization, we applied a comparative proteomics approach to screen for
      neuropeptide changes in a rodent model of AMPH-induced sensitization. By
      measuring peptide profiles with matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry and comparing signal intensities using principal
      component analysis and variance statistics, subsets of peptides are found with
      significant differences in the dorsal striatum, nucleus accumbens, and medial
      prefrontal cortex of AMPH-sensitized male Sprague-Dawley rats. These biomarker
      peptides, identified in follow-up analyses using liquid chromatography and tandem
      mass spectrometry, suggest that behavioral sensitization to AMPH is associated
      with complex chemical adaptations that regulate energy/metabolism,
      neurotransmission, apoptosis, neuroprotection, and neuritogenesis, as well as
      cytoskeleton integrity and neuronal morphology. Our data contribute to a growing
      number of reports showing that in addition to the mesolimbic dopamine system,
      which is the best known signaling pathway involved with reinforcing the effect of
      psychostimulants, concomitant chemical changes in other pathways and in neuronal
      organization may play a part in the overall effect of chronic AMPH exposure on
      behavior.

PMID- 22860607
TI  - Effects of carotid artery stenosis treatment on blood pressure.
AB  - OBJECT: The purpose of this study was to evaluate and compare the long-term
      effects of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on
      blood pressure (BP). METHODS: Between January 2003 and December 2009, 134
      patients underwent 145 procedures for treatment of carotid artery stenosis.
      Patients with at least 1 year of clinical and radiographic follow-up after
      treatment were included in this study. A total of 102 patients met this criterion
      and were placed in the CEA group (n = 59) or the CAS group (n = 43) according to
      their treatment. The percentage change in BP decrement and the number of patients
      with a normotensive BP were evaluated and compared between the groups. RESULTS:
      There were no significant differences between the groups with regard to baseline
      characteristics. Compared with the pretreatment BP, the follow-up BPs were
      significantly decreased in both groups. At the 1-year followup, the percentage
      change in the BP decrement was greater in the CAS group (percentage change:
      systolic BP 9.6% and diastolic BP 12.8%) than in the CEA group (percentage
      change: systolic BP 5.9% [p = 0.035] and diastolic BP = 8.1% [p = 0.049]), and
      there were more patients with a normotensive BP in the CAS group (46.5%) than in
      the CEA group (22.0%, p = 0.012). CONCLUSIONS: Both CEA and CAS have BP-lowering
      effects. Carotid artery stenting seems to have a better effect than CEA on BP at
      the 1-year follow-up.

PMID- 22860608
TI  - Editorial: traumatic brain injury and brainstem.

PMID- 22860609
TI  - Jasmonoyl-L-isoleucine hydrolase 1 (JIH1) regulates jasmonoyl-L-isoleucine levels
      and attenuates plant defenses against herbivores.
AB  - For most plant hormones, biological activity is suppressed by reversible
      conjugation to sugars, amino acids and other small molecules. In contrast, the
      conjugation of jasmonic acid (JA) to isoleucine (Ile) is known to enhance the
      activity of JA. Whereas hydroxylation and carboxylation of JA-Ile permanently
      inactivates JA-Ilemediated signaling in plants, the alternative deactivation
      pathway of JA-Ile by its direct hydrolysis to JA remains unstudied. We show that
      Nicotiana attenuata jasmonoyl-L-isoleucine hydrolase 1 (JIH1), a close homologue
      of previously characterized indoleacetic acid alanine resistant 3 (IAR3) gene in
      Arabidopsis, hydrolyzes both JA-Ile and IAA-Ala in vitro. When the herbivory
      inducible NaJIH1 gene was silenced by RNA interference, JA-Ile levels increased
      dramatically after simulated herbivory in irJIH1, compared with wild-type (WT)
      plants. When specialist (Manduca sexta) or generalist (Spodoptera littoralis)
      herbivores fed on irJIH1 plants they gained significantly less mass compared with
      those feeding on wild-type (WT) plants. The poor larval performance was strongly
      correlated with the higher accumulation of several JA-Ile-dependent direct
      defense metabolites in irJIH1 plants. In the field, irJIH1 plants attracted
      substantially more Geocoris predators to the experimentally attached M. sexta
      eggs on their leaves, compared with empty vector plants, which correlated with
      higher herbivory-elicited emissions of volatiles known to function as indirect
      defenses. We conclude that NaJIH1 encodes a new homeostatic step in JA metabolism
      that, together with JA and JA-Ilehydroxylation and carboxylation of JA-Ile,
      rapidly attenuates the JA-Ile burst, allowing plants to tailor the expression of
      direct and indirect defenses against herbivore attack in nature.

PMID- 22860610
TI  - Commentary: simvastatin as the key to improving H. pylori eradication rates?

PMID- 22860612
TI  - Commentary: endoscopic dilatation for stricturing Crohn's disease.

PMID- 22860613
TI  - Letter: anti-TNFs and psoriasis--friends or foes?

PMID- 22860615
TI  - Letter: infliximab and adalimumab in the management of Crohn's disease--are they
      really comparable?

PMID- 22860616
TI  - Letter: persistence of anti-infliximab antibodies after discontinuation of
      infliximab in patients with IBD.

PMID- 22860618
TI  - Accelerated junctional rhythm and nonalternans repolarization lability precede
      ventricular tachycardia in Casq2-/- mice.
AB  - BACKGROUND: Calsequestrin-2 (CASQ2) is a Ca(2+) buffering protein of myocardial
      sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic
      polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated
      in Casq2 -/- mice. Repolarization lability (RL)-beat-to-beat variability in the T
      wave morphology-has been reported in long-QT syndrome, but has not been evaluated
      in CPVT. METHODS AND RESULTS: ECG from Casq2 -/- mice was evaluated with respect
      to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT)
      to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice
      (3-month-old males, 5 animals of each genotype) and ECG before and after
      isoproterenol administration in anesthetized mice was analyzed. Average HR in
      sinus rhythm (SR), occurrence of nonsinus rhythm and RL were quantified. HR was
      slower in Casq2 -/- animals. Accelerated junctional rhythm (JR) occurred more
      frequently in Casq2 -/- mice and often preceded VT. In Casq2 -/- mice, HR
      increased prior to VT onset, prior to onset of JR and on transition from JR to
      VT. RL increased during progression from SR to VT and after isoproterenol
      administration in Casq2 -/-, but not in Casq2+/+ animals. Isoproterenol did not
      increase repolarization alternans in either genotype. CONCLUSIONS: Accelerated
      JR, likely caused by triggered activity in His/Purkinje system, occurs frequently
      in Casq2 -/- mice. The absence of CASQ2 results in increased RL. The increase in
      HR and in RL precede onset of arrhythmias in this CPVT model. Nonalternans RL
      precedes ventricular arrhythmia in wider range of conditions than previously
      appreciated.

PMID- 22860619
TI  - Tomato contact dermatitis.
AB  - The tomato plant (Solanum lycopersicum) is an important crop worldwide. Whereas
      immediate-type reactions to tomato fruits are well known, contact dermatitis
      caused by tomatoes or tomato plants is rarely reported. The aims of this study
      were to present new data on contact sensitization to tomato plants and review the
      literature on contact dermatitis caused by both plants and fruits. An ether
      extract of tomato plants made as the original oleoresin plant extracts, was used
      in aimed patch testing, and between 2005 and 2011. 8 of 93 patients (9%) tested
      positive to the oleoresin extracts. This prevalence is in accordance with the
      older literature that reports tomato plants as occasional sensitizers. The same
      applies to tomato fruits, which, in addition, may cause protein contact
      dermatitis. The allergens of the plant are unknown, but both heat-stable and heat
      labile constituents seem to be involved. The fruit contains fragrance compounds
      that are also present in Myroxylon pereirae (balsam of Peru), possibly accounting
      for cross-reactivity. The proteins in pulp and peel may contribute to protein
      contact dermatitis. Until more is known about the allergens, the diagnosis of
      contact dermatitis caused by tomato plants and fruit may be established with the
      use of ether extracts and fresh fruits, respectively.

PMID- 22860621
TI  - Guidelines for the management of vitiligo: the European Dermatology Forum
      consensus.
AB  - The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this
      has held back progress in diagnosis and treatment. Up until now, treatment
      guidelines have existed at national levels, but no common European viewpoint has
      emerged. This guideline for the treatment of segmental and nonsegmental vitiligo
      has been developed by the members of the Vitiligo European Task Force and other
      colleagues. It summarizes evidence-based and expert-based recommendations (S1
      level).

PMID- 22860622
TI  - Spanking and child development during the first 5 years of life.
AB  - Using data from the Fragile Families and Child Wellbeing Study (N=3,870) and
      cross-lagged path analysis, the authors examined whether spanking at ages 1 and 3
      is adversely associated with cognitive skills and behavior problems at ages 3 and
      5. The authors found spanking at age 1 was associated with a higher level of
      spanking and externalizing behavior at age 3, and spanking at age 3 was
      associated with a higher level of internalizing and externalizing behavior at age
      5. The associations between spanking at age 1 and behavioral problems at age 5
      operated predominantly through ongoing spanking at age 3. The authors did not
      find an association between spanking at age 1 and cognitive skills at age 3 or 5.

PMID- 22860623
TI  - The elder-friendly emergency department assessment tool: development of a quality
      assessment tool for emergency department-based geriatric care.
AB  - OBJECTIVES: To develop and conduct a preliminary validation of selected subscales
      of an elder-friendly emergency department (ED) assessment tool. DESIGN: Content
      validation of tool by an international panel. Construct validation using care
      ratings of ED lead physicians and nurses. SETTING: Quebec, Canada. PARTICIPANTS:
      The international panel comprised 34 clinicians, administrators, and researchers.
      The construct validation was based on a 2006 survey of ED lead physicians and
      nurses at all 103 EDs in the province, of whom 68 (66%) supplied complete data.
      MEASUREMENTS: The initial tool included five subscales: ED staffing, screening
      and assessment, discharge planning, community services, and care philosophy.
      Differences in subscale scores were examined according to ED size, and of these
      scores were correlated with care ratings made by lead physicians and nurses.
      RESULTS: The average scores for three subscales (ED staffing, discharge planning,
      and community services) varied according to ED size. After adjustment for ED
      size, three subscales (screening and assessment, discharge planning, and
      community services) were correlated with ED nurse or physician care ratings. A
      preliminary tool, taking into account all factors, is proposed. CONCLUSION: This
      study provides preliminary evidence of the validity of three subscales of the
      proposed elder-friendly ED assessment tool. Results suggest that ED size should
      be considered in interpreting these subscales. Further evaluation and validation
      of the proposed tool will be needed to further its utility in helping to focus
      the quality improvement efforts of clinicians, managers, and administrators
      related to the care they provide older adults.

PMID- 22860624
TI  - Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes.
AB  - A powerful Fe(III)/NaBH(4)-mediated free radical hydrofluorination of unactivated
      alkenes is disclosed using Selectfluor reagent as a source of fluorine and
      resulting in exclusive Markovnikov addition. In contrast to the traditional and
      unmanageable free radical hydrofluorination of alkenes, the Fe(III)/NaBH(4)
      mediated reaction is conducted under exceptionally mild reaction conditions (0 
      degrees C, 5 min, CH(3)CN/H(2)O). The reaction can be conducted open to the air
      and with water as a cosolvent and demonstrates an outstanding substrate scope and
      functional group tolerance.

PMID- 22860625
TI  - Impact of hyponatremia on survival of patients with metastatic renal cell
      carcinoma treated with molecular targeted therapy.
AB  - OBJECTIVES: Hyponatremia is reported to be associated with poor survival in
      localized renal cell carcinoma and metastatic renal cell carcinoma treated with
      immunotherapy. However, there are no reports on the relationship between
      hyponatremia and prognosis of metastatic renal cell carcinoma treated with
      molecular targeted therapy. We evaluated the prognostic significance of
      hyponatremia in metastatic renal cell carcinoma treated with molecular targeted
      therapy as first-line therapy. METHODS: We retrospectively analyzed a database
      comprising 87 patients treated from April 2008 to July 2011 with sorafenib or
      sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients
      were divided into three groups according to serum sodium level: severe
      hyponatremia (<=134 mEq/L), mild hyponatremia (135-137 mEq/L) and normal natremia
      (>=138 mEq/L). RESULTS: Median cancer-specific survival time was 8.8 months in
      the patients with severe and mild hyponatremia, and 32.6 months in the patients
      with normal natremia (P < 0.001). Multivariate analysis showed severe and mild
      hyponatremia to be significantly associated with cancer-specific survival (hazard
      ratio 6.228; 95% confidence interval 2.161-17.947, P = 0.001; hazard ratio 3.374;
      95% confidence interval 1.294-8.798, P = 0.013), respectively. Neutrophilia and
      high C-reactive protein level (C-reactive protein >=1.0 mg/dL) were significant
      prognostic factors to predict inferior cancer-specific survival. In Harrell's
      concordance index calculation, hyponatremia could significantly improve the
      predictive accuracy for estimation of survival probability (P = 0.028).
      CONCLUSIONS: Hyponatremia (<138 mEq/L), neutrophilia and high C-reactive protein
      levels seem to represent significant predictive factors for cancer-specific
      survival in metastatic renal cell carcinoma patients treated with molecular
      targeted therapy as first line therapy. Furthermore, hyponatremia might be
      significantly associated with chronic inflammation and tumor aggressiveness.

PMID- 22860627
TI  - Angiogenesis-related agents in esophageal cancer.
AB  - INTRODUCTION: Esophageal cancer is an aggressive disease with poor prognosis. The
      majority of the patients are diagnosed at an advanced stage and many with early
      stage disease will develop recurrent disease. AREAS COVERED: Angiogenesis is
      essential to the progress and aggressiveness of solid malignancies. Success of
      anti-angiogenic therapy in colorectal, lung and breast cancers is a proof of
      principle. Thus far, evidence for benefit from anti-angiogenic therapy in
      esophageal cancer is lacking. Several Phase II trials with different agents have
      provided mixed results and the only Phase III trial in the esophageal and gastric
      cancer failed to show that these agents improve overall survival (OS). However,
      lack of observed benefit could be due to the challenges specific to the
      management of esophageal cancers as well as issues with the design of clinical
      trials for anti-angiogenic therapy. EXPERT OPINION: An understanding of the
      biology of the esophageal cancer and its management is essential to the
      development of anti-angiogenic therapy in this disease. This article reviews the
      management of esophageal cancer and elaborates on the challenges in the
      development of anti-angiogenic therapy in esophageal cancer. At the end,
      strategies are proposed for successful development of anti-angiogenic therapy in
      esophageal cancer.

PMID- 22860626
TI  - Stereological assessment of the dorsal anterior cingulate cortex in
      schizophrenia: absence of changes in neuronal and glial densities.
AB  - AIMS: The prefrontal and anterior cingulate cortices are implicated in
      schizophrenia, and many studies have assessed volume, cortical thickness, and
      neuronal densities or numbers in these regions. Available data, however, are
      rather conflicting and no clear cortical alteration pattern has been established.
      Changes in oligodendrocytes and white matter have been observed in schizophrenia,
      introducing a hypothesis about a myelin deficit as a key event in disease
      development. METHODS: We investigated the dorsal anterior cingulate cortex (dACC)
      in 13 men with schizophrenia and 13 age- and gender-matched controls. We assessed
      stereologically the dACC volume, neuronal and glial densities, total neurone and
      glial numbers, and glia/neurone index (GNI) in both layers II-III and V-VI.
      RESULTS: We observed no differences in neuronal or glial densities. No changes
      were observed in dACC cortical volume, total neurone numbers, and total glial
      numbers in schizophrenia. This contrasts with previous findings and suggests that
      the dACC may not undergo as severe changes in schizophrenia as is generally
      believed. However, we observed higher glial densities in layers V-VI than in
      layers II-III in both controls and patients with schizophrenia, pointing to
      possible layer-specific effects on oligodendrocyte distribution during
      development. CONCLUSIONS: Using rigorous stereological methods, we demonstrate a
      seemingly normal cortical organization in an important neocortical area for
      schizophrenia, emphasizing the importance of such morphometric approaches in
      quantitative neuropathology. We discuss the significance of subregion- and layer
      specific alterations in the development of schizophrenia, and the discrepancies
      between post mortem histopathological studies and in vivo brain imaging findings
      in patients.

PMID- 22860628
TI  - MAP0004: dihydroergotamine mesylate inhalation aerosol for acute treatment of
      migraine.
AB  - INTRODUCTION: Dihydroergotamine mesylate (DHE) has been used as an acute migraine
      treatment since 1945, although tolerability with intravenous administration has
      limited its use. MAP0004 is a novel, orally inhaled, aerosol formulation of DHE
      that provides pulmonary drug delivery using a pressurized, metered dose inhaler
      for rapid absorption through lung alveoli. MAP0004 was developed to provide the
      anti-migraine efficacy of DHE, with fewer systemic effects than intravenous
      dosing. AREAS COVERED: This review discusses available literature describing the
      pharmacokinetics, tolerability and efficacy of MAP0004, including data from Phase
      II and Phase III clinical trials. EXPERT OPINION: MAP0004 aerosol DHE provides
      desirable activation of 5-HT1B/D receptors, resulting in effective anti-migraine
      effects. Unlike intravenous DHE, MAP0004 is less likely to bind with other
      serotonergic, adrenergic and dopaminergic receptors, resulting in fewer unwanted
      side effects. In addition, MAP0004 is less arterioconstrictive than intravenous
      DHE. Both Phase II and III clinical trials support anti-migraine efficacy with
      superior tolerability with MAP0004 compared with intravenous DHE. Inhaled rather
      than intravenous administration should also improve patient acceptance. These
      data support the future use of MAP0004 as a first-line acute migraine treatment.

PMID- 22860629
TI  - The cellular form of the prion protein is involved in controlling cell cycle
      dynamics, self-renewal, and the fate of human embryonic stem cell
      differentiation.
AB  - Prion protein (PrP(C) ), is a glycoprotein that is expressed on the cell surface.
      The current study examines the role of PrP(C)  in early human embryogenesis using
      human embryonic stem cells (hESCs) and tetracycline-regulated lentiviral vectors
      that up-regulate or suppresses PrP(C)  expression. Here, we show that expression
      of PrP(C)  in pluripotent hESCs cultured under self-renewal conditions induced
      cell differentiation toward lineages of three germ layers. Silencing of PrP(C) 
      in hESCs undergoing spontaneous differentiation altered the dynamics of the cell
      cycle and changed the balance between the lineages of the three germ layers,
      where differentiation toward ectodermal lineages was suppressed. Moreover, over
      expression of PrP(C)  in hESCs undergoing spontaneous differentiation inhibited
      differentiation toward lineages of all three germ layers and helped to preserve
      high proliferation activity. These results illustrate that PrP(C)  is involved in
      key activities that dictate the status of hESCs including regulation of cell
      cycle dynamics, controlling the switch between self-renewal and differentiation,
      and determining the fate of hESCs differentiation. This study suggests that
      PrP(C)  is at the crossroads of several signaling pathways that regulate the
      switch between preservation of or departure from the self-renewal state, control
      cell proliferation activity, and define stem cell fate.

PMID- 22860630
TI  - Does a surgeon's annual radical prostatectomy volume predict the risk of positive
      surgical margins and urinary incontinence at one-year follow-up? Findings from a
      prospective national study.
AB  - OBJECTIVE: This study aimed to assess the prevalence of positive surgical margins
      (PSM) and urinary incontinence (UI) in relation to surgeons' annual radical
      prostatectomy (RP) volume. MATERIAL AND METHODS: This national study
      prospectively assessed 521 preoperatively continent patients with prostate cancer
      (PCa), scheduled for RP by surgeons with high (>50), medium (20-50) or low annual
      volume (<20) at 14 urological departments in Norway. Patients responded to UI
      questions from the Expanded Composite prostate cancer index (EPIC-50) before and
      1 year after RP. UI was defined as "use of pad(s)" and/or "a moderate or severe
      urinary leakage problem (ULP)". Preoperative prediction of PSMs and UI was
      explored in multivariate regression analyses with the following independent
      variables: surgeons' annual RP volume, type of hospital (university versus
      community), patient's health, sociodemographic features and PCa characteristics.
      RESULTS: Based on histopathological reports, the overall PSM rate was 26%, with
      differences between the high- (18%), medium- (28%) and low-volume (44%) groups.
      Increasing PSM rates were predicted by surgeons belonging to the low- and medium
      volume categories, prostate-specific antigen> 10 ug/l, Gleason score >7, patient
      age >65 years and <12 years of education. At 1-year follow-up 40% reported UI,
      without significant differences between the volume groups. Only 46% of those who
      used pad(s) experienced ULP. UI was predicted by clinical category >=T2 and
      community type of hospital, but not by surgeons' annual RP volume. CONCLUSIONS.
      Preoperative counselling should take into account the relationship between
      surgeon's annual RP volume and PSM rate and the current knowledge about UI and
      ULP.

PMID- 22860631
TI  - Tricuspid annular plane systolic excursion (TAPSE) in dogs: reference values and
      impact of pulmonary hypertension.
AB  - BACKGROUND: The impact of pulmonary hypertension (PH) on right ventricular
      systolic function is difficult to assess. Tricuspid annular plane systolic
      excursion (TAPSE) is an echocardiographic measurement of right ventricular
      systolic function and a strong predictor of outcome in human PH patients.
      HYPOTHESIS/OBJECTIVES: Determine a reference range for TAPSE in healthy dogs, and
      quantify TAPSE in dogs with PH. It is hypothesized that TAPSE is lower in dogs
      with PH compared with a reference group, and decreases as PH worsens. ANIMALS:
      Fifty normal dogs and 30 dogs with PH. METHODS: TAPSE was measured by 2
      dimensional echocardiography-guided M-mode from the left apical 4-chamber view.
      Peak systolic tricuspid valve regurgitation jet velocity was measured by
      continuous-wave Doppler to estimate right ventricular-to-right atrial pressure
      gradient. PH was subjectively classified as mild, moderate, and severe. RESULTS:
      There was a curvilinear correlation between TAPSE and body weight. The upper and
      lower limits of the 95% reference interval were determined by quantile
      regression. Interobserver and intraobserver agreement was adequate with a
      coefficient of variation <10%. There were significant differences when comparing
      dogs with PH and the healthy group, as well as between the PH subgroups (P <
      .01), except between dogs with mild and moderate PH (P = .99). Only dogs in the
      severe PH group had TAPSE values that were mostly below the lower limit of the
      reference interval. CONCLUSIONS AND CLINICAL IMPORTANCE: TAPSE is easily
      obtainable with acceptable inter and intraobserver agreement. TAPSE is decreased
      in PH and below the reference interval in most dogs with severe PH.

PMID- 22860632
TI  - Phenolic compositions of grapes and wines from cultivar cAbernet Sauvignon
      produced in Chile and their relationship to commercial value.
AB  - The phenolic composition of wine depends on, among other factors, the grapes used
      to make it. In this sense, knowledge of the chemical composition of grapes and
      its association with the resulting wines is an important tool to determine if
      there is a relationship between the phenolic composition of grapes and the price
      that these wines obtain in the market. For this purpose, grape skins and seeds
      from the cultivar Cabernet Sauvignon from the central region of Chile, in 2009
      and 2010 vintages from two ripening points, were subjected to chemical and
      phenolic analyses, as were the wines made from these grapes. Grapes and the
      corresponding wines from three retail price wine categories, U.S. $6-8, U.S. $28
      30, and U.S. $150-160, were evaluated. No differences were found across the price
      categories in the chemical analysis of grapes. Berry skins and wines from the
      higher price categories presented a higher concentration only of total tannins,
      and the differences in their concentrations were only among the different
      fractions of proanthocyanidins in the skins, seeds, and wines; there were no
      differences in their proportions. A seasonal effect influenced the concentrations
      of certain compounds in grapes and led to a decrease in the concentration of
      total phenols, total tannins, and total anthocyanins between sampling dates as
      harvesting moved toward the common commercial grape harvest in Chilean
      viticulture.

PMID- 22860633
TI  - Emulsion templating of poly(lactic acid) particles: droplet formation behavior.
AB  - Monodisperse poly(DL-lactic acid) (PLA) particles of diameters between 11 and 121
      MUm were fabricated in flow focusing glass microcapillary devices by evaporation
      of dichloromethane (DCM) from emulsion droplets at room temperature. The
      dispersed phase was 5% (w/w) PLA in DCM containing 0.1-2 mM Nile Red and the
      continuous phase was 5% (w/w) poly(vinyl alcohol) in reverse osmosis water.
      Particle diameter was 2.7 times smaller than the diameter of the emulsion droplet
      template, indicating very low particle porosity. Monodisperse droplets have only
      been produced under dripping regime using a wide range of dispersed phase flow
      rates (0.002-7.2 cm(3).h(-1)), continuous phase flow rates (0.3-30 cm(3).h(-1)),
      and orifice diameters (50-237 MUm). In the dripping regime, the ratio of droplet
      diameter to orifice diameter was inversely proportional to the 0.39 power of the
      ratio of the continuous phase flow rate to dispersed phase flow rate. Highly
      uniform droplets with a coefficient of variation (CV) below 2% and a ratio of the
      droplet diameter to orifice diameter of 0.5-1 were obtained at flow rate ratios
      of 4-25. Under jetting regime, polydisperse droplets (CV > 6%) were formed by
      detachment from relatively long jets (between 4 and 10 times longer than droplet
      diameter) and a ratio of the droplet size to orifice size of 2-5.

PMID- 22860635
TI  - No evidence for treating friends' children like kin in Canadian androphilic men.
AB  - Given that same-sex sexual orientation is associated with lower reproductive
      success, how have genes associated with male androphilia (i.e., male sexual
      attraction/arousal to adult men) persisted over evolutionary time? The Kin
      Selection Hypothesis proposes that by directing valuable resources toward kin,
      androphilic men may enhance their indirect fitness and thereby offset the fitness
      costs of not reproducing directly. Support for this hypothesis has been garnered
      from studies conducted in Samoa, but not from studies of "gay" men in
      industrialized cultures (i.e., Canada, Japan, United Kingdom, and the United
      States). This cross-cultural difference may be due to relatively greater
      geographic and familial disconnect experienced by androphilic "gay" men in
      industrialized cultures. This article reasons that in more industrialized
      settings, friends' children may serve as non-adaptive proxies for nieces and
      nephews. Hence, it was predicted that Canadian androphilic men would exhibit
      elevated altruistic tendencies toward their friends' children compared with
      gynephilic men and androphilic women. This prediction was not supported. However,
      in line with previous research, the results indicated that androphilic women are
      more likely to behave altruistically toward friends' children compared to
      gynephilic men. Other possible explanations for the existing cross-cultural
      discrepancy in altruistic tendencies toward nieces and nephews are discussed. 

PMID- 22860634
TI  - Assembly of four diverse heterocyclic libraries enabled by Prins cyclization, Au
      catalyzed enyne cycloisomerization, and automated amide synthesis.
AB  - We describe a unified synthetic strategy for efficient assembly of four new
      heterocyclic libraries. The synthesis began by creating a range of structurally
      diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple
      one-flask operation starting with readily available amines, ketoesters, and
      unsaturated anhydrides. The use of tetrahydropyran-containing ketoesters, which
      were rapidly assembled by our Prins cyclization protocol, enabled efficient
      fusion of pyran and piperidinone cores. A newly developed Au(I)-catalyzed
      cycloisomerization of alkyne-containing enamides further expanded heterocyclic
      diversity by providing rapid entry into a wide range of bicyclic and tricyclic
      dienamides. The final stage of the process entailed diversification of each of
      the initially produced carboxylic acids using a fully automated platform for
      amide synthesis, which delivered 1872 compounds in high diastereomeric and
      chemical purity.

PMID- 22860636
TI  - Measuring the sustainability of a community safety promotion network: working
      from the inside out.
AB  - Mackay Whitsunday Safe Communities (MWSC) was developed using a capacity building
      model that consciously attempted to design sustainability into the network. Our
      aim was to quantify the flow of resources used by MWSC to implement and sustain
      its injury control activities. Resource exchange among network members was
      quantified and analysed using social network analysis. In 2004, MWSC accessed an
      estimated 6.5 full-time staff equivalents and $0.9 million. However, these
      resources were largely accessed externally. The linking relationships that
      connected MWSC to its external support network, more than half of which were
      maintained by six broker network facilitators, were the critical social asset
      used to access resources and sustain network productivity. The sustainability of
      this network and arguably similar safety promotion networks is vulnerable to the
      changing priorities of external sponsoring agents and highly dependent on its
      leaders who facilitated access to the resources it required to remain productive.

PMID- 22860637
TI  - Treatment of steroid-induced elevated intraocular pressure with anecortave
      acetate: a randomized clinical trial.
AB  - PURPOSE: The present study is the first randomized clinical trial designed to
      evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate
      (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot
      (AJD) in patients experiencing elevated IOP due to corticosteroid therapy.
      METHODS: This was a double-masked, randomized, placebo-controlled, multicenter,
      parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP
      increase of at least 10 mmHg relative to their IOP before treatment with
      steroids. A target IOP was established for each patient at baseline. Patients
      were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30
      mg AA. All patients then received a 0.5 mL AJD of the assigned treatment.
      Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3,
      4, 5, and 6. IOP was measured at each visit as well as best corrected visual
      acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination,
      and assessment of any adverse events. In addition, at baseline and at exit, a
      dilated fundus examination was carried out and the lens was examined using LOCS
      II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4,
      eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline.
      Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg,
      16.6%) were not significantly different than for vehicle control. However, IOP
      for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline,
      which was statistically significant (P=0.0487). The mean time to treatment
      failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA,
      and 30 mg AA groups, respectively. Adverse events were assessed at each post
      treatment visit. There were no serious adverse events that were determined to be
      related to the test article or its administration. CONCLUSIONS: AA can be of
      benefit to some patients requiring treatment with corticosteroids, but suffering
      from the side effect of elevated IOP.

PMID- 22860688
TI  - 4,5-Bis(dimethylamino)quinolines: proton sponge versus azine behavior.
AB  - Two first representatives, 5 and 6, of the still unknown 4,5
      bis(dimethylamino)quinoline have been synthesized and studied. While the former,
      being protonated either at the peri-NMe(2) groups or at the ring nitrogen, has
      been shown to display properties of both a proton sponge and azine, its
      counterpart 6 behaves exclusively as azine giving only a quinolinium salt.

PMID- 22860689
TI  - The requirement for recombination factors differs considerably between different
      pathways of homologous double-strand break repair in somatic plant cells.
AB  - In recent years, multiple factors involved in DNA double-strand break (DSB)
      repair have been characterised in Arabidopsis thaliana. Using homologous
      sequences in somatic cells, DSBs are mainly repaired by two different pathways:
      synthesis-dependent strand annealing (SDSA) and single-strand annealing (SSA). By
      applying recombination substrates in which recombination is initiated by the
      induction of a site-specific DSB by the homing endonuclease I-SceI, we were able
      to characterise the involvement of different factors in both pathways. The
      nucleases MRE11 and COM1, both involved in DSB end processing, were not required
      for either SDSA or SSA in our assay system. Both SDSA and SSA were even more
      efficient without MRE11, in accordance with the fact that a loss of MRE11 might
      negatively affect the efficiency of non-homologous end joining. Loss of the
      classical recombinase RAD51 or its two paralogues RAD51C and XRCC3, as well as
      the SWI2/SNF2 remodelling factor RAD54, resulted in a drastic deficiency in SDSA
      but had hardly any influence on SSA, confirming that a strand exchange reaction
      is only required for SDSA. The helicase FANCM, which is postulated to be involved
      in the stabilisation of recombination intermediates, is surprisingly not only
      needed for SDSA but to a lesser extent also for SSA. Both SSA and SDSA were
      affected only weakly when the SMC6B protein, implicated in sister chromatid
      recombination, was absent, indicating that SSA and SDSA are in most cases
      intrachromatid recombination reactions.

PMID- 22860690
TI  - Is the subjective perception of lactose intolerance influenced by the
      psychological profile?
AB  - BACKGROUND: Symptoms of lactose intolerance are often attributed to lactose
      malabsorption but, as this relationship has not been demonstrated when a small
      dose of lactose similar to that contained in one cup of milk is ingested by
      intolerant patients, psychological factors may play a role in altered symptom
      perception. AIM: To assess the hypothesis that the psychological profile
      influences the symptoms of lactose intolerance. METHODS: One hundred and two
      consecutive patients underwent a 15 g lactose hydrogen breath test to assess
      lactose malabsorption. The patients recorded the presence and severity of
      symptoms of lactose intolerance during the breath test using visual analogue
      scales. The psychological profile was assessed using a psychological symptom
      checklist, and health-related quality of life by means of the short-form health
      survey. RESULTS: Lactose malabsorption and intolerance were diagnosed in,
      respectively, 18% and 29% of the patients. The two conditions were not
      associated, and the severity of intolerance was even less in the patients with
      malabsorption. Multivariate logistic analysis showed that a high somatisation t
      score was significantly associated with lactose intolerance (odds ratio 4.184;
      1.704-10.309); the effects of the other psychological variables and of lactose
      malabsorption were not statistically significant. Health-related quality of life
      was significantly reduced in the patients with somatisation, but not in those
      with lactose malabsorption. CONCLUSIONS: The symptoms of lactose intolerance
      during hydrogen breath testing at a low physiological lactose load, are unrelated
      to lactose malabsorption, but may reveal a tendency towards somatisation that
      could impair the quality of life.

PMID- 22860691
TI  - Effect of nonmagnetic substitution on the magnetic properties and charge-transfer
      phase transition of an iron mixed-valence complex, (n
      C3H7)4N[Fe(II)Fe(III)(dto)3] (dto = C2O2S2).
AB  - The iron mixed-valence complex (n-C(3)H(7))(4)N[Fe(II)Fe(III)(dto)(3)] exhibits a
      novel type of phase transition called charge-transfer phase transition (CTPT),
      where the thermally induced electron transfer between Fe(II) and Fe(III) occurs
      reversibly at ~120 K, in addition to the ferromagnetic phase transition at T(C) =
      7 K. To investigate the mechanism of the CTPT, we have synthesized a series of
      magnetically diluted complexes (n-C(3)H(7))(4)N[Fe(II)(1
      x)Zn(II)(x)Fe(III)(dto)(3)] (dto = C(2)O(2)S(2); x = 0-1), and carried out
      magnetic susceptibility and dielectric constant measurements and (57)Fe Mossbauer
      spectroscopy. With increasing Zn(II) concentration (x), the CTPT is gradually
      suppressed and disappears at x ~ 0.13. On the other hand, the ferromagnetic
      transition temperature (T(C)) is initially enhanced from 7 K to 12 K between x =
      0.00 and 0.05, despite the nonmagnetic nature of Zn(II) ions, and then it
      decreases monotonically from 12 K to 3 K with increasing Zn(II) concentration.
      This anomalous dependence of T(C) on Zn(II) concentration is related to a change
      in the spin configuration of the ferromagnetic state caused by the partial
      suppression of the CTPT.

PMID- 22860692
TI  - Low rate of secondary prevention ICDs in the general population: multiple-year
      multiple-source surveillance of sudden cardiac death in the Oregon Sudden
      Unexpected Death Study.
AB  - INTRODUCTION: Sudden cardiac death (SCD) is a large public health problem that
      warrants on-going evaluation in the general population. While single-year
      community-based studies have been performed there is a lack of studies that have
      extended evaluation to multiple years in the same community. METHODS AND RESULTS:
      From the on-going Oregon Sudden Unexpected Death Study, we analyzed prospectively
      identified SCD cases in Multnomah County, Ore, (population ~700,000) from
      February 1, 2002 to January 31, 2005. Detailed information ascertained from
      multiple sources (first responders, clinical records, and medical examiner) was
      analyzed. A total of 1,175 SCD cases were identified (61% male) with a mean age
      of 65 +/- 18 years for men versus 70 +/- 20 for women (P < 0.001). The overall
      incidence rate for the period was 58/100,000 residents/year. One-quarter (24.6%)
      was <= 55 years of age. The most common initial rhythm was ventricular
      tachycardia or fibrillation (39% of cases, survival 27%) followed by asystole
      (36%, survival 0.7%) and pulseless electrical activity (23%, survival 6%). Among
      subjects that underwent resuscitation, the rate of survival to hospital discharge
      was 12% and overall survival to hospital discharge irrespective of resuscitation
      was 8%. Of the 68 survivors, 16 (24%) received a secondary prevention ICD.
      CONCLUSION: We report annualized SCD incidence from a multiple-year, multiple
      source community-based study, with higher than expected rates of women and
      subjects age <= 55 years. The low implantation rate of secondary prevention ICDs
      is likely to be multifactorial, but there are potential implications for
      recalibration of the projected need for ICD implantation; larger and more
      detailed studies are warranted.

PMID- 22860693
TI  - Efficacy and safety of a new apple-flavoured oral rehydration solution in
      children with acute gastroenteritis: a double-blind randomized controlled trial.
AB  - AIM:   To assess the efficacy and safety of a new oral rehydration solution (ORS)
      with improved flavour in the management of children with acute gastroenteritis
      (AGE). METHODS:   Children 4 to 48 months of age with AGE (>=3 loose or watery
      stools per day for >1 but <5 days) with mild-to-moderate dehydration (3% to 9%
      loss of body weight) according to the World Health Organization criteria randomly
      received regular hypotonic ORS (Na 60 mmol/L, glucose 78 mmol/L) or the same
      hypotonic ORS with an apple taste. RESULTS:   Of the 147 children randomized, 130
      (88.4%) were available for intention-to-treat analysis. The proportion of
      children with the resolution of signs of dehydration in the experimental group
      compared with the control group was similar at 24 h (49/63 vs. 57/67,
      respectively, p = 0.28). There were also no significant differences in adequate
      weight gain (p = 0.48) and urine production at 24 h (p = 0.95) between groups.
      There were no differences between groups in any of the secondary outcome
      measures, including ORS intake. No adverse events were observed in the study
      groups. CONCLUSIONS:   In an outpatient setting, there was no difference in
      efficacy between the study products. Both ORSs were equally effective and may be
      used interchangeably.

PMID- 22860695
TI  - The prevalence of thyroid disease in patients with vitiligo: a systematic review.
AB  - BACKGROUND: Thyroid disease has been suggested to be associated with vitiligo.
      However, the outcomes of prevalence studies on thyroid disease in vitiligo vary
      widely. OBJECTIVES: To summarize and critically appraise current evidence of the
      prevalence of thyroid diseases in vitiligo. METHODS: A systematic review was
      performed searching the electronic databases OVID MEDLINE, OVID EMBASE and
      PubMed. Guidelines for the critical appraisal of studies on prevalence of a
      health problem were adapted to evaluate the methodological quality of the
      included studies. Results were analysed in a meta-analysis with a risk ratio
      (RR). RESULTS: Forty-eight studies published between 1968 and 2012 met the
      inclusion criteria. Most of the studies (50%) were of fair methodological
      quality, whereas 18 studies (38%) were of poor quality and six studies (12%) were
      of good quality. Thyroid disease, autoimmune thyroid disease and presence of
      thyroid-specific autoantibodies showed a mean prevalence of, respectively, 15.1%,
      14.3% and 20.8% in patients with vitiligo and an RR of, respectively, 1.9, 2.5
      and 5.2 (all statistically significant). This review shows an increased
      prevalence and an increased risk of (autoimmune) thyroid disease in patients with
      vitiligo compared with nonvitiligo. This risk seems to increase with age.
      CONCLUSIONS: Clinicians should be aware of this increased risk in patients with
      vitiligo and should be attentive for symptoms of thyroid disease. To make
      recommendations on screening for thyroid disease in patients with vitiligo future
      research of good methodological quality, including differentiation of vitiligo
      types and the use of standardized outcome measures, is needed.

PMID- 22860694
TI  - Short communication: prevalence of HIV type 1 transmitted drug resistance in
      Slovenia: 2005-2010.
AB  - Slovenia is a small European country with a total of 547 HIV-infected individuals
      cumulatively reported by the end of 2011. However, the estimated incidence rate
      of HIV infections increased from 7.0 per million in 2003 to 26.8 per million in
      2011. In this study, we assessed the prevalence of transmitted drug resistance
      (TDR) in the past 6 years (2005-2010) and analyzed the time trend of the
      proportion of men having sex with men (MSM) and HIV-1 subtype B among newly
      diagnosed individuals in a 15-year period (1996-2010) in Slovenia. Among 150
      patients included in the study, representing 63% of HIV-1 newly diagnosed
      patients in 2005-2010, TDR was found in seven patients (4.7%). The prevalence of
      TDR to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse
      transcriptase inhibitors, and protease inhibitors was 2% (3/150), 2% (3/150), and
      0.7% (1/150), respectively. The majority of patients were infected with subtype B
      (134/150, 89%), while subtype A was detected in 6.0% (9/150), subtype D in 1.3%
      (2/150), and subtype G and CRF02_AG in 0.7% (one patient each). Three of 150
      sequences could not be typed. Infection with subtype B was found to be
      significantly associated with male gender, Slovenia being reported as the country
      of the patient's nationality and origin of the virus, CDC class A, mode of
      transmission with homosexual/bisexual contact, sex with an anonymous person, and
      a higher CD4(+) count. Among patients carrying the subtype B virus, an MSM
      transmission route was reported in 87% of patients. Although the prevalence of
      TDR in Slovenia is still below the European average, active surveillance should
      be continued, especially among MSM, the most vulnerable population for HIV-1
      infection in this part of Europe.

PMID- 22860696
TI  - Risk of fatal injury in older adult drivers, passengers, and pedestrians.
AB  - OBJECTIVES: To compare risk of fatal injury in elderly road users (drivers,
      passengers, pedestrians) with that of younger age groups and to assess the
      contribution of elderly road users to the number of reported fatalities in the
      population. DESIGN: Fatality age was categorized as 21 to 29, 30 to 39, 40 to 49,
      50 to 59, 60 to 69, or 70 and older, and road user was categorized as driver,
      passenger, or pedestrian. Estimated number of trips made by each age group was
      used to adjust for exposure and to measure individual risk. SETTING: Fatalities
      recorded in Britain between 1989 and 2009. PARTICIPANTS: Population-wide fatal
      injury counts in Britain. MEASUREMENTS: Age of fatally injured drivers,
      passengers, and pedestrians. Estimated number of trips made per year by drivers,
      passengers, and pedestrians. RESULTS: Risk of fatal injury, but not fatality
      numbers in the population, were higher for older adult (>= 70) drivers than for
      younger age groups. Risk of fatal injury was also high for older adult passengers
      and pedestrians, who represented the majority of older adult fatalities.
      CONCLUSION: Previous emphasis on driver impairment in older age has unduly
      focussed attention on elderly drivers, who represent a minority of all driver
      fatalities. Older adults represent a much larger proportion of passenger and
      pedestrian fatalities. Additional policy schemes and initiatives should be
      targeted at safeguarding older adult passengers and making the road environment
      safer for elderly pedestrians.

PMID- 22860697
TI  - Rh-catalyzed intermolecular carbenoid functionalization of aromatic C-H bonds by
      alpha-diazomalonates.
AB  - A Rh-catalyzed intermolecular coupling of diazomalonates with arene C-H bonds is
      reported. The reaction is initiated by electrophilic C-H activation, which is
      followed by coupling of the arylrhodium(III) complex with the diazomalonate. In
      most cases, arenes with oximes, carboxylic acids, and amines as directing groups
      cross-couple with diazomalonates with excellent regioselectivities and functional
      group tolerance, and thus, this reaction offers a new route to alpha-aryl
      carbonyl compounds for specific applications.

PMID- 22860698
TI  - Spirulina as a livestock supplement and animal feed.
AB  - Spirulina (Athrospira sp.) is an edible microalga and a highly nutritious
      potential feed resource for many agriculturally important animal species.
      Research findings have associated Spirulina to improvements in animal growth,
      fertility, aesthetic and nutritional product quality. Spirulina intake has also
      been linked to an improvement in animal health and welfare. Its influence over
      animal development stems from its nutritive and protein-rich composition, thus
      leading to an increased commercial production to meet consumer demand.
      Consequently, Spirulina is emerging as a cost-effective means of improving animal
      productivity for a sustainable and viable food security future. However, our
      present knowledge of animal response to dietary Spirulina supplementation is
      relatively scanty and largely unknown. Therefore, the primary objective of this
      paper was to review past and current findings on the utilisation of Spirulina as
      a feed supplement and its impact on animal productivity and health. Only animals
      deemed to be of agricultural significance were investigated; hence, only
      ruminants, poultry, swine and rabbits and their responses to dietary Spirulina
      supplementation are covered.

PMID- 22860699
TI  - Efficacy of intranasal administration of a modified live feline herpesvirus 1 and
      feline calicivirus vaccine against disease caused by Bordetella bronchiseptica
      after experimental challenge.
AB  - BACKGROUND: Studies suggest that intranasal vaccination can stimulate nonspecific
      immunity against agents not contained within the vaccine, but this effect is not
      reported for cats. HYPOTHESIS: A modified live feline herpesvirus-1 (FHV-1) and
      feline calicivirus (FCV) intranasal vaccine will reduce clinical signs of disease
      caused by experimental infection with Bordetella bronchiseptica. ANIMALS: Twenty
      specific pathogen-free 12-week-old kittens. METHODS: Experimental study. Cats
      were randomized into 2 groups of 10 cats each. The vaccinated group was
      administered a single intranasal dose of a commercially available vaccine
      containing modified live strains of FHV-1 and FCV, and the control group remained
      unvaccinated. All 20 cats were administered B. bronchiseptica by nasal
      inoculation 7 days later and were observed daily for clinical signs of illness
      for 20 days. RESULTS: In the first 10 days after B. bronchiseptica challenge,
      vaccinated cats were less likely to be clinically ill than control cats with a
      median clinical score of 0/180 (range 0-5) versus 2/180 (range 0-8) (P = .01).
      Nine of 10 control cats and 2 of 10 vaccinated cats were recorded as sneezing
      during days 1-10 after challenge (P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Intranasal vaccination against FHV-1 and FCV decreased signs of illness due to an
      infectious agent not contained in the vaccine. This nonspecific immunity could be
      beneficial for protection against organisms for which vaccines are not available
      and as protection before development of vaccine-induced humoral immunity.

PMID- 22860700
TI  - Optineurin is potentially associated with TDP-43 and involved in the pathogenesis
      of inclusion body myositis.
AB  - AIMS: Increasing evidences suggest a similarity in the pathophysiological
      mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and
      myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this
      study is to elucidate the involvement of ALS-causing proteins in the
      pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens
      of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD),
      three with polymyositis (PM), three with dermatomyositis (DM), three with
      neurogenic muscular atrophy, and three healthy control subjects were examined. We
      analysed the expression and localization of familial ALS-causing proteins,
      including transactive response DNA binding protein-43 (TDP-43), fused in
      sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1)
      and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a
      lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in
      patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular
      atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage
      of myofibres in patients with sIBM and OPMD, and to a very small extent in
      patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins
      more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau.
      CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be
      involved in the pathophysiological mechanisms of skeletal muscular degeneration
      in myopathy with rimmed vacuoles. Further investigation into these mechanisms is
      therefore warranted.

PMID- 22860701
TI  - Oaxacan women with HIV/AIDS: resiliency in the face of poverty, stigma, and
      social isolation.
AB  - ISSUES: HIV infection among Mexican women continues to increase. The purpose of
      the authors in this study was to explore the psychosocial issues of HIV-infected
      Mexican women's lives, and to support a request from the Mexican federal
      government for data to support the need for funding for the psychological care of
      these women. METHODS: A Spanish-speaking researcher conducted private, in-depth,
      face-to-face interviews with 21 women receiving health services at the HIV/AIDS
      clinic, COESIDA, near Oaxaca City, Mexico. Data were collected during the time
      period of January 17 through 21st, 2011. The authors ascertained socio
      demographic characteristics for all study participants. They transcribed audio
      taped interviews verbatim, translated them into English, and analyzed transcribed
      interviews using content analysis, identifying consistent themes across the
      interviews. They also conducted language and cultural verification of the
      translation, and a third person, a master's prepared native Mexican woman,
      conducted content analysis. RESULTS: Ages of participants ranged from 20 to 48
      years, with most having a third grade education. Most women lived at least two
      hours from the clinic. Themes emerging from the interview transcript analysis
      included: (1) resiliency; (2) fear; (3) social isolation; (4) anger/rage; and (5)
      availability of resources and support. CONCLUSION: Despite facing a variety of
      adverse factors, the Oaxacan women with HIV/AIDS who were interviewed
      demonstrated a sense of resiliency and hope for the future. Yet, a critical need
      remains for mental health support services to be provided to women to assist them
      in managing the psychological consequences of their HIV/AIDS diagnosis.

PMID- 22860702
TI  - Postpartum cultural practices are negatively associated with depressive symptoms
      among Chinese and Vietnamese immigrant mothers married to Taiwanese men.
AB  - The objectives of researchers in this study were to examine acceptance and
      adherence to mainstream Taiwanese postpartum cultural practices and their
      association with postpartum depressive symptoms among Chinese and Vietnamese
      immigrant mothers married to Taiwanese men. While the postpartum cultural
      practices in China are similar to mainstream Taiwanese practices, those of
      Vietnam differ from Taiwanese practices. This cross-sectional survey was
      conducted in Taiwan from October 2007 through March 2008, and included190
      immigrant mothers from China and Vietnam who had delivered a child within the
      past year. Immigrant mothers from China had higher levels of acceptance and
      adherence to mainstream Taiwanese postpartum cultural practices and a lower rate
      of postpartum depressive symptoms than immigrant mothers from Vietnam, but the
      association between adherence to "doing-the-month" practices and postpartum
      depressive symptoms did not vary significantly between Chinese and Vietnamese
      mothers. Adherence to these practices was negatively associated with postpartum
      depressive symptoms among immigrant mothers (OR = 0.93, 95% CI: 0.90-0.96) after
      adjustment for social support, duration between moving to Taiwan and delivery,
      and country of origin. Adherence to mainstream postpartum cultural practices was
      negatively associated with postpartum depressive symptoms for both Chinese and
      Vietnamese immigrant women married to Taiwanese men.

PMID- 22860703
TI  - Evaluating race/ethnicity in moderating baseline cardiometabolic risk and body
      composition changes in North Carolina first-year college women.
AB  - The roles of race/ethnicity and geographical region in the context of first-year
      college weight gain remain largely under-examined. The present study evaluated
      whether race/ethnicity: (1) at baseline was associated with greater
      representation in cardiometabolic health risk categories for body mass index,
      percent body fat, waist circumference, and waist-to-hip ratio in the full sample
      of 54 Black/African American and 80 White/European American first-year female
      undergraduates attending a North Carolina state university; and (2) moderated
      body composition changes between the beginning of the fall and spring semesters
      among the 83 participants who completed baseline and follow-up visits (N = 39
      Black/African Americans). More Black/African Americans than White/European
      Americans had percent body fat values >=32% at baseline; a greater proportion of
      White/European Americans than Black/African Americans had a waist-to-hip ratio
      >0.80. Among those who completed baseline and follow-up visits, White/European
      Americans had higher waist-to-hip ratios (unadjusted: p <0.01, adjusted for
      family income: p < 0.01) and waist circumferences (adjusted for family income: p
      < 0.05) at both time points. No strong moderating effects of race/ethnicity were
      detected. Preliminary results suggested that greater consideration of
      racial/ethnic indicators and potential regional variation in these biometric
      attributes among first-year college students is warranted.

PMID- 22860704
TI  - Examining barriers to and motivations for substance abuse treatment among
      pregnant women: does urban-rural residence matter?
AB  - Barriers to entering and motivations for substance abuse treatment were examined
      among rural and urban pregnant women. All pregnant women entering inpatient
      detoxification at the University of Kentucky Medical Center were approached about
      participating in a study on health and well-being. One hundred fourteen (N = 114)
      pregnant women voluntarily participated. Treatment barriers and motivators were
      measured with open-ended questions. The Treatment Attitude Profile quantitatively
      measured motivation. Both groups reported approximately two treatment barriers.
      Top treatment motivators were pregnancy (65.8%), needing help (23.7%), family
      (18.4%), and being tired of the lifestyle (16.7%). Overall, Treatment Attitude
      Profile scores were fairly high (Mean = 74.3, SD = 10.7), representing motivation
      for treatment. Multivariate analyses revealed a significant negative relationship
      between treatment motivation and gestational age (beta = -0.233; p = 0.012), and
      a positive relationship between treatment motivation and reporting an
      acceptability barrier (e.g., denial, stigma) (beta = 0.202; p = 0.024). Few
      between group differences existed in barriers and treatment motivation.
      Individuals residing in rural areas have unique beliefs, social ties, attitudes,
      and financial hardships. Research about the role of these factors in treatment
      access and motivation could be used to minimize treatment barriers.

PMID- 22860705
TI  - Barriers to screening for intimate partner violence.
AB  - BACKGROUND: Health care providers play a vital role in the detection of intimate
      partner violence among their patients. Despite the recommendations for routine
      intimate partner violence screening in various medical settings, health care
      providers do not routinely screen for intimate partner violence. The authors
      wanted to identify barriers to intimate partner violence screening and improve
      the understanding of intimate partner violence screening barriers among different
      health care providers. METHODS: The authors conducted a systematic review to
      examine health care providers' perceived barriers to screening for intimate
      partner violence. By grouping the studies into two time periods, based on date of
      publication, they examined differences in the reported barriers to intimate
      partner violence screening over time. RESULTS: The authors included a total of 22
      studies in this review from all examined sources. Five categories of intimate
      partner violence screening barriers were identified: personal barriers, resource
      barriers, perceptions and attitudes, fears, and patient-related barriers. The
      most frequently reported barriers included personal discomfort with the issue,
      lack of knowledge, and time constraints. Provider-related barriers were reported
      more often than patient-related barriers. CONCLUSIONS: Barriers to screening for
      intimate partner violence are numerous among health care providers of various
      medical specialties. Increased education and training regarding intimate partner
      violence is necessary to address perceptions and attitudes to remove barriers
      that hinder intimate partner violence screening by health care providers.

PMID- 22860706
TI  - Mental health and family functioning as correlates of a sedentary lifestyle among
      low-income women with young children.
AB  - The authors in this cross-sectional study examined mental health and family
      environmental factors related to a sedentary lifestyle, including lack of leisure
      time physical activity and high levels of television viewing, among low-income
      mothers/female guardians of preschool-aged children. A self-administered
      questionnaire was completed by 131 mothers in 2010. Primary outcome measures
      included television viewing time (minutes/day) and leisure-time physical activity
      (<150 versus >=150 minutes per week). Independent variables included depressive
      symptoms, perceived stress, and family functioning. Demographic factors (age,
      marriage, work status, education, number of children in the household, and
      race/ethnicity) were examined as potential covariates. Participating women
      watched television on average 186.1 minutes/day (i.e., >3 hours). Additionally,
      36% of women engaged in less than the recommended 150-minute leisure-time
      physical activity per week. Hierarchical multiple regression analyses indicated
      that greater depressive symptoms (B = 76.4, p < 0.01) and lower family
      functioning (B = 33.0, p < 0.05) were independently related to greater television
      viewing when controlling for other variables. No independent factors were
      identified for lack of leisure-time physical activity when controlling for other
      covariates. Findings suggest that health promotion efforts to promote an active
      lifestyle among low-income women with young children should address mental health
      and family functioning factors, especially depressive symptoms.

PMID- 22860708
TI  - Simultaneous decoloration and deproteinization of crude polysaccharide from
      pumpkin residues by cross-linked polystyrene macroporous resin.
AB  - A novel method for the purification of crude polysaccharide from fermentation
      broth of pumpkin residues by macroporous resins was developed. Through static
      adsorption and desorption and adsorption kinetic tests, six resins (AB-8, S-8,
      HPH480, HPD100, X-5, and D101) with different polarity, diameter, and surface
      area were studied for simultaneous decoloration and deproteinization of crude
      polysaccharide, and S-8 was chosen as the best one. Dynamic breakthrough and
      desorption tests were performed in a glass column packed with S-8 resin, and the
      resulting adsorption ratios of pigment and protein were 84.3% and 75.9% (w/w),
      respectively, with a recovery ratio of polysaccharide 84.7% (w/w). S-8 resin also
      exhibited higher purification efficiency than the other tested traditional
      methods. Moreover, UV/vis spectroscopy (200-900 nm) analysis revealed most of the
      pigment and protein were absorbed by S-8 resin, and HPLC (containing a refractive
      index detector and a HPSEC column) results indicated that there was no
      degradation of the polysaccharide. This automated and efficient method via
      adsorption-desorption strategy could have potential in scale-up purification and
      preparation of polysaccharide in the future. 

PMID- 22860709
TI  - S-1 for the treatment of gastrointestinal cancer.
AB  - INTRODUCTION: 5-Fluorouracil (5-FU)-based regimens are used worldwide as the
      standard treatment in chemotherapy for gastric cancer. S-1 , a fourth-generation
      oral fluoropyrimidine that combines tegafur and two biochemical modulators:
      gimeracil and oteracil potassium, is now attracting considerable interest. AREAS
      COVERED: This review addresses the clinical evidence of S-1 in gastrointestinal
      malignancies, such as gastric, colorectal, pancreatic and biliary tract cancers.
      S-1 has demonstrated advantages over standard therapies, in both advanced and
      postoperative settings, in large Phase III studies. S-1 alone or S-1 plus
      cisplatin is recommended in the 2010 Gastric Cancer Treatment Guidelines, by the
      Japanese Gastric Cancer Association. Results from Phase III studies have
      demonstrated that S-1 in combination with chemotherapies, such as cisplatin in
      gastric cancer, and irinotecan and oxaliplatin in colorectal cancers, is non
      inferior to conventional 5-FU-based standard regimens, with the benefit of
      convenience and reduced toxicity. EXPERT OPINION: The excellent design of S-1
      aimed to reduce toxicity by avoiding certain routes of degradation, and to
      enhance activity by reducing catabolism. This has provided not only a suitable
      alternative to 5-FU, but also higher efficacy.

PMID- 22860710
TI  - Dispersion of multiwalled carbon nanotubes in water using ionic-complementary
      peptides.
AB  - We demonstrate the noncovalent modification of multiwalled carbon nanotubes
      (MWNTs) immersed in aqueous solution using the ionic-complementary peptide EFK16
      II. This modification presumably arises through the interaction between the
      hydrophobic side of the EFK16-II and MWNT sidewalls and orients hydrophilic
      functional groups toward the solution phase and enables them to form highly
      stable dispersions in water. This stability can be attributed to the
      electrostatic repulsion between self-assembled peptides on the MWNTs. This
      repulsion as determined by zeta potential measurements increases as the pH
      diverges from the isoelectric point of ~6.7 for EFK16-II. This trend is confirmed
      by dynamic light scattering measurements of the suspensions showing a decrease in
      their particle size as the zeta potential increases. These EFK16-II-MWNT
      suspensions have been used to modify mica surfaces. Atomic force microscopy and
      scanning electron microscopy images show that this leads to a uniform
      distribution of individual modified MWNTs on the mica surfaces. Transmission
      electron microscopy reveals images of well-dispersed fibers with dimensions
      similar to those of individual MWNTs. Tissue culture plates previously contacted
      with EFK16-II-modified MWNTs have been shown to have enough biocompatibility for
      growth and attachment of cells. The biocompatibility and enhanced electrical
      conductivity that should result from the modification with these EFK16-II-MWNT
      suspensions opens up their use in a number of potential biomedical applications
      such as the design of bioelectrode interfaces and fabrication of biosensors with
      high sensitivity.

PMID- 22860711
TI  - Cross-coupling of diarylborinic acids and anhydrides with arylhalides catalyzed
      by a phosphite/N-heterocyclic carbene co-supported palladium catalyst system.
AB  - A highly efficient cross-coupling of diarylborinic acids and anhydrides with aryl
      chlorides and bromides has been effected by using a palladium catalyst system co
      supported by a strong sigma-donor N-heterocyclic carbene (NHC), N,N'-bis(2,6
      diisopropylphenyl) imidazol-2-ylidene, and a strong pi-acceptor phosphite,
      triphenylphosphite, in tert-BuOH in the present of K(3)PO(4).3H(2)O.
      Unsymmetrical biaryls with a variety of functional groups could be obtained in
      good to excellent yields using as low as 0.01, 0.2-0.5, and 1 mol % palladium
      loadings for aryl bromides and activated and deactivated aryl chlorides,
      respectively, under mild conditions. A ligand synergy between the sigma-donor NHC
      and the pi-acceptor phosphite in the Pd/NHC/P(OPh)(3) catalytic system has been
      proposed to be responsible for the high efficacy to arylchlorides in the cross
      coupling. A scalable and economical process has therefore been developed for
      synthesis of Sartan biphenyl from the Pd/NHC/P(OPh)(3) catalyzed cross-coupling
      of di(4-methylphenyl)borinic acid with 2-chlorobenzonitrile.

PMID- 22860712
TI  - Growth in externalizing and internalizing problems in childhood: a prospective
      study of psychopathology across three generations.
AB  - Three generations of participants were assessed over approximately 27 years, and
      intergenerational prediction models of growth in the third generation's (G3)
      externalizing and internalizing problems across ages 3-9 years were examined. The
      sample included 103 fathers and mothers (G2), at least 1 parent (G1) for all of
      the G2 fathers (99 mothers, 72 fathers), and 185 G3 offspring (83 boys, 102
      girls) of G2, with prospective data available on the G2 fathers beginning at age
      9 years. Behavior of the G2 mother, along with father contact and mother age at
      birth were included in the models. Intergenerational associations in
      psychopathology were modest, and much of the transmission occurred via contextual
      risk within the family of procreation.

PMID- 22860713
TI  - Synthesis of amphiphilic brookite nanoparticles with high photocatalytic
      performance for wide range of application.
AB  - Brookite TiO(2) nanoparticles with amphiphilic properties were successfully
      synthesized with a water-soluble titanium glycolate complex precursor using an
      oleate-modified hydrothermal growth process. The ~20-40 nm TiO(2) nanoparticles
      were highly dispersible in both water and cyclohexane. The activity of the
      brookite nanoparticles for the degradation of acetaldehyde under UV irradiation
      was higher than that of Degussa P-25 TiO(2) powder. A spin-coated brookite film
      prepared on a polyimide substrate exhibited photoinduced hydrophilicity. Thus,
      these synthesized brookite nanoparticles could be applied as a photocatalytic
      coating solution.

PMID- 22860714
TI  - Deuterated matrix-assisted laser desorption ionization matrix uncovers masked
      mass spectrometry imaging signals of small molecules.
AB  - D(4)-alpha-Cyano-4-hydroxycinnamic acid (D(4)-CHCA) has been synthesized for use
      as a matrix for matrix-assisted laser desorption ionization-mass spectrometry
      (MALDI-MS) and MALDI-MS imaging (MSI) of small molecule drugs and endogenous
      compounds. MALDI-MS analysis of small molecules has historically been hindered by
      interference from matrix ion clusters and fragment peaks that mask signals of low
      molecular weight compounds of interest. By using D(4)-CHCA, the cluster and
      fragment peaks of CHCA, the most common matrix for analysis of small molecules,
      are shifted by + 4, + 8 and + 12 Da, which expose signals across areas of the
      previously concealed low mass range. Here, obscured MALDI-MS signals of a
      synthetic small molecule pharmaceutical, a naturally occurring isoquinoline
      alkaloid, and endogenous compounds including the neurotransmitter acetylcholine
      have been unmasked and imaged directly from biological tissue sections.

PMID- 22860716
TI  - The association of the metabolic profile in diabetes mellitus type 2 patients
      with obsessive-compulsive symptomatology and depressive symptomatology: new
      insights.
AB  - OBJECTIVE: The aim of the present study was to explore the relationship between
      diabetes mellitus type 2, Obsessive- compulsive disorder (OCD) symptomatology and
      depressive symptomatology with the metabolic profile of diabetic patients.
      METHODS: One hundred and thirty-one diabetic patients were randomly selected. In
      the first assessment all participants completed the Zung Self Rating Scale (ZUNG)
      and the Maudsley O-C Inventory Questionnaire (MOCI). After 1 year, diabetic
      patients that were initially uncontrolled (n = 31) (HbA1c > 7) were re-evaluated
      by the same psychometric tools. From those 31 patients, 10 had managed to control
      their metabolic profile. RESULTS: In the first evaluation MOCI and the sub-scale
      of slowness were statistically related with the diabetic profile (controlled,
      HbA1c <= 7; uncontrolled, HbA1c > 7), with uncontrolled patients scoring
      significantly higher on the overall MOCI score and the factor of slowness of MOCI
      scale (P = 0.028). The analysis revealed a positive association between
      depressive symptomatology (P = 0.004) and obsessive-compulsive disorder
      symptomatology (P < 0.001) and the metabolic profile of the patients. In the
      second evaluation the patients that managed to control their metabolic profile
      scored lower in both ZDRS and MOCI, although these differences in scores failed
      to reach significance levels were indicative of a tendency. CONCLUSIONS: The
      present results provide initial evidence that diabetes mellitus type 2 is
      associated with obsessive-compulsive disorder symptomatology and depressive
      symptomatology.

PMID- 22860715
TI  - Mammographic breast density and serum phytoestrogen levels.
AB  - Some forms of estrogen are associated with breast cancer risk as well as with
      mammographic density (MD), a strong marker of breast cancer risk. Whether
      phytoestrogen intake affects breast density, however, remains unclear. We
      evaluated the association between serum levels of phytoestrogens and MD in
      postmenopausal women. We enrolled 269 women, ages 55-70 yr, who received a
      screening mammogram and had no history of postmenopausal hormone use. Subjects
      completed a survey on diet and factors related to MD and provided a blood sample
      for analysis of 3 phytoestrogens: genistein, daidzein, and coumestrol. We
      examined whether mean percent MD was related to serum level of phytoestrogens,
      adjusting for age and body mass index. Genistein and daidzein levels correlated
      with self-reported soy consumption. Mean percent MD did not differ across women
      with different phytoestrogen levels. For example, women with nondetectable
      genistein levels had mean density of 11.0% [95% confidence intervals (CI) = 9.9
      12.4], compared to 10.5% (95% CI = 8.0-13.7) and 11.2% (95% CI = 8.7-14.6) for <
      and >= median detectable levels, respectively. In a population with relatively
      low soy intake, serum phytoestrogens were not associated with mammographic
      density. Additional studies are needed to determine effects of higher levels,
      particularly given patterns of increasing phytoestrogen intake.

PMID- 22860717
TI  - Thermoresponsive shuttling of rotaxane containing trichloroacetate ion.
AB  - A thermoresponsive rotaxane shuttling system was developed with a
      trichloroacetate counteranion of an ammonium/crown ether-type rotaxane.
      Chemoselective thermal decomposition of the ammonium trichloroacetate moiety on
      the rotaxane yielded the corresponding nonionic rotaxane accompanied by a
      positional change of the crown ether on the axle. The rotaxane skeleton
      facilitated effective dissociation of the acid, markedly lowering the thermal
      decomposition temperature.

PMID- 22860750
TI  - Effects of self-esteem on electrophysiological correlates of easy and difficult
      math.
AB  - The current study investigated the effects of easy versus difficult math on event
      related potentials as a function of self-esteem in 28 undergraduate students.
      First, it was found that participants responded much more rapidly to an easy
      task. Second, the amplitude of P2 (150-300 ms) was more positive amplified in low
      self-esteem participants when compared to high self-esteem participants. Third,
      the difficult task elicited a greater N2 (300-450 ms) component than the easy
      task, but only in the low self-esteem participants. Finally, the easy task
      elicited a greater late positive component (LPC: 450-600 ms) compared with the
      difficult task and the difficult task elicited a greater LPC (900-1200 ms)
      components compared with the easy task separately, which were consistent with
      behavioral reaction times. We speculate that the difficult math might have
      induced more negative emotions in subjects with low self-esteem, and that low
      self-esteem individuals might be more susceptible to interpret the difficult task
      as threatening. 

PMID- 22860749
TI  - Functional genomic and high-content screening for target discovery and
      deconvolution.
AB  - INTRODUCTION: Functional genomic screens apply knowledge gained from the
      sequencing of the human genome toward rapid methods of identifying genes involved
      in cellular function based on a specific phenotype. This approach has been made
      possible through advances in both molecular biology and automation. The utility
      of this approach has been further enhanced through the application of image-based
      high-content screening: an automated microscopy and quantitative image analysis
      platform. These approaches can significantly enhance the acquisition of novel
      targets for drug discovery. AREAS COVERED: Both the utility and potential issues
      associated with functional genomic screening approaches are discussed in this
      review, along with examples that illustrate both. The considerations for high
      content screening applied to functional genomics are also presented. EXPERT
      OPINION: Functional genomic screening and high-content screening are extremely
      useful in the identification of new drug targets. However, the technical,
      experimental, and computational parameters have an enormous influence on the
      results. Thus, although new targets are identified, caution should be applied to
      the interpretation of screening data in isolation. Genomic screens should be
      viewed as an integral component of a target identification campaign that requires
      both the acquisition of orthogonal data, as well as a rigorous validation
      strategy.

PMID- 22860751
TI  - Early and late studies of EMD use in periodontal intrabony defects.
AB  - BACKGROUND AND OBJECTIVE: The clinical efficacy of EMDs for the treatment of
      periodontal infrabony defects has been reported. However, recent publications
      have questioned the validity of results from early findings. Hence, the purpose
      of this study was to compare the results obtained from early and late studies
      when EMD was used as an adjunct in treating human intrabony defects during flap
      surgery. The aim of this meta-analysis was to evaluate the validity of results
      published from early studies compared with those published from later studies.
      MATERIAL AND METHODS: PubMed and MEDLINE searches were performed. The evaluation
      period was 1997-2010 and it was divided into two groups of equal periods of time:
      early studies (1997-2003) and late studies (2004-2010). The clinical parameters
      assessed were clinical attachment level (CAL), probing pocket depth and bone gain
      (BG; measured as a percentage or in mm). RESULTS: No statistically significant
      difference was found between the results obtained from early studies (1997-2003)
      and late studies (2004-2010) with regards to CAL gain, probing pocket depth
      reduction and BG. Nonetheless, both study periods showed a benefit for using EMD
      to treat periodontal infrabony defects when compared with the groups without EMD
      during open flap surgery. CONCLUSIONS: The results obtained from this study
      failed to show any potential differences between the results published from early
      studies and late studies with regards to the clinical effectiveness of EMD in
      treating periodontal infrabony defects.

PMID- 22860752
TI  - Peroxisome proliferator-activated receptor gamma agonists reduce cell
      proliferation and viability and increase apoptosis in systemic sclerosis
      fibroblasts.
AB  - BACKGROUND:  No study has evaluated the effect of the peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists on cell viability, proliferation
      and apoptosis in cultured systemic sclerosis (SSc) fibroblasts. OBJECTIVES: The
      effects of two pure PPARgamma agonists (rosiglitazone and pioglitazone) in
      cultured SSc fibroblasts were evaluated and compared with effects in normal
      fibroblasts. METHODS:  The study included evaluation of cell viability and
      proliferation (based on the cleavage of tetrazolium salts and measurement of
      absorbance of the cell proliferation reagent WST-1), and determination of cell
      apoptosis (by means of the Hoechst dye uptake). RESULTS: Rosiglitazone or
      pioglitazone (20MUmolL(-1) ) significantly reduced cell proliferation (cell count
      of 75% and 83% compared with baseline, respectively, after 2h) and cell viability
      (absorbance reductions of 25% and 22% compared with baseline, respectively, after
      2 h), and increased apoptosis (apoptotic cell percentages 9.9% and 8.6%,
      respectively, after 48h of incubation) in SSc fibroblasts, whereas they did not
      present a significant influence on control fibroblasts. CONCLUSIONS: The effects
      of rosiglitazone or pioglitazone shown on SSc fibroblasts raise the hypothesis of
      a therapeutic role for PPARgamma agonists in patients affected by SSc.

PMID- 22860753
TI  - Three-dimensional finite element analysis of occlusal stress distribution in the
      human skull with premolar extraction.
AB  - OBJECTIVE: To analyze the effect of orthodontic treatment with premolar
      extraction on the stress distribution of the occlusal force in the human skull.
      MATERIALS AND METHODS: A three-dimensional finite element (3D FE) model was
      constructed based on computed tomography scan data, and it served as the
      pretreatment model. For the extraction model simulating postorthodontic
      occlusion, the first premolar was removed in the pretreatment model, and the
      anterior and posterior segments were repositioned. Stress distribution was
      evaluated by 3D FE analysis in both models under the simulation of 1000 N for
      occlusal forces and 400 N for masseter muscle force. RESULTS: The occlusal
      stresses were concentrated at the alveolar bone near the teeth, the
      infrazygomatic crest, the frontal process, the temporal process of the zygomatic
      bone, the infraorbital rim, the pyriform aperture region, and the pterygoid plate
      in both models. The von Mises stress at the pterygoid plate area was lower in the
      extraction model (3.53 MPa) than in the pretreatment model (5.57 MPa), while the
      stress at the frontal process of the maxilla was higher in the extraction model
      (2.32 MPa) than in the pretreatment model (2.16 MPa). CONCLUSIONS: The results
      indicated that the occlusal forces were transferred through the maxillonasal,
      maxillozygomatic, and maxillopterygoid stress trajectories and that stress
      distribution moved more "forward" with the orthodontic treatment with premolar
      extraction.

PMID- 22860754
TI  - Role of nanomechanics in canonical and noncanonical pro-angiogenic ligand/VEGF
      receptor-2 activation.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR2) is an endothelial cell
      receptor that plays a pivotal role in physiologic and pathologic angiogenesis and
      is a therapeutic target for angiogenesis-dependent diseases, including cancer. By
      leveraging on a dedicated nanomechanical biosensor, we investigated the nanoscale
      mechanical phenomena intertwined with VEGFR2 surface recognition by its
      prototypic ligand VEGF-A and its noncanonical ligand gremlin. We found that the
      two ligands bind the immobilized extracellular domain of VEGFR2 (sVEGFR2) with
      comparable binding affinity. Nevertheless, they interact with sVEGFR2 with
      different binding kinetics and drive different in-plane piconewton intermolecular
      forces, suggesting that the binding of VEGF-A or gremlin induces different
      conformational changes in sVEGFR2. These behaviors can be effectively described
      in terms of a different "nanomechanical affinity" of the two ligands for sVEGFR2,
      about 16-fold higher for VEGF-A with respect to gremlin. Such nanomechanical
      differences affect the biological activity driven by the two angiogenic factors
      in endothelial cells, as evidenced by a more rapid VEGFR2 clustering and a more
      potent mitogenic response triggered by VEGF-A in respect to gremlin. Together,
      these data point to surface intermolecular interactions on cell membrane between
      activated receptors as a key modulator of the intracellular signaling cascade.

PMID- 22860755
TI  - Survival analysis.
AB  - AIMS AND OBJECTIVES: This paper describes when and why survival analysis is used
      and describes the use and interpretation of the techniques most commonly
      encountered in medical literature. This is performed using examples taken from
      core medical journals. BACKGROUND: Survival analysis is widely used in clinical
      and epidemiological research: in randomised clinical trials for comparing the
      efficacy of treatments and in observational (non-randomised) research to
      determine and test the existence of epidemiological association. DESIGN: This
      paper introduces the principles, practice and terminology of survival analysis.
      METHODS: References are made to examples from open-access medical journals.
      RESULTS: Survival analysis is a well-established series of methodologies that are
      widely encountered in medical literature for both observational and randomised
      studies. CONCLUSIONS: Survival analysis represents a more efficient use of
      clinical data than other forms of analysis which rely on fixed time periods. One
      of the most widely used techniques is that developed by Kaplan and Meier. This
      involves the creation of life tables and the plotting of survival curves with
      comparison made between two or more groups. The log-rank test is commonly used to
      establish whether there is a statistically significant difference between these
      groups. The Multivariate Cox proportional hazards extend this approach to give an
      estimate of effect size (the Hazards Ratio) and can adjust for any potential
      confounding variables. In this model, the assumption of proportional hazards is
      of key importance and should always be checked. More advanced techniques are the
      use of time-dependent variables and the less widely used parametric survival
      techniques. Care should always be taken when considering the assumptions involved
      when using such methods. RELEVANCE TO CLINICAL PRACTICE: As survival analysis is
      widely used in clinical research, it is important that readers can critically
      evaluate the use of this technique.

PMID- 22860756
TI  - Effect of a restorative model of posthospital home care on hospital readmissions.
AB  - OBJECTIVES: To compare readmissions of Medicare recipients of usual home care and
      a matched group of recipients of a restorative model of home care. DESIGN:
      Quasiexperimental; matched and unmatched. SETTING: Community, home care.
      PARTICIPANTS: Seven hundred seventy individuals receiving care from a large home
      care agency after hospitalization. INTERVENTION: A restorative care model based
      on principles adapted from geriatric medicine, nursing, rehabilitation, goal
      attainment, chronic care management, and behavioral change theory. MEASUREMENTS:
      Hospital readmission, length of home care episode. RESULTS: Among the matched
      pairs, 13.2% of participants who received restorative care were readmitted to an
      acute hospital during the episode of home care, versus 17.6% of those who
      received usual care. Individuals receiving the restorative model of home care
      were 32% less likely to be readmitted than those receiving usual care
      (conditional odds ratio = 0.68, 95% confidence interval = 0.43-1.08). The mean
      length of home care episodes was 20.3 +/- 14.8 days in the restorative care group
      and 29.1 +/- 31.7 days in the usual care group (P < .001). Results were similar
      in unmatched analyses. CONCLUSION: Although statistical significance was
      marginal, results suggest that the restorative care model offers an effective
      approach to reducing the occurrence of avoidable readmissions. It was previously
      shown that the restorative model of home care was associated with better
      functional recovery, fewer emergency department visits, and shorter episodes of
      home care. This model could be incorporated into usual home care practices and
      care delivery redesign.

PMID- 22860758
TI  - Childcare and behavioural outcomes.

PMID- 22860757
TI  - Mapping of epitopes relevant for induction of acrosome reaction on human zona
      pellucida glycoprotein-4 using monoclonal antibodies.
AB  - PROBLEM: To decipher structural and functional aspects of human zona pellucida
      glycoprotein-4 (ZP4), the epitopes recognized by monoclonal antibodies (MAbs)
      have been mapped. METHOD OF STUDY: Recombinant human ZP4-mediated induction of
      acrosome reaction in human sperm was studied in the absence and presence of ZP4
      specific MAbs. The epitopes of MAbs were mapped using recombinant peptides
      expressed in Escherichia coli. RESULTS: Monoclonal antibodies (MA-1662, MA-1671)
      against human ZP4 showed specific binding to ZP matrix of human eggs in an
      indirect immunofluorescence assay. Both the antibodies showed significant (P <
      0.05) inhibition in the baculovirus-expressed recombinant ZP4-mediated acrosome
      reaction. MA-1671 recognized N-terminal fragment of ZP4 and minimal epitope
      mapped to amino acid residues 126-130 (PARDR), whereas MA-1662 reacted to C
      terminal fragment and minimal epitope mapped to amino acid residues 256-260
      (ENELV). CONCLUSIONS: The epitopes corresponding to both N- and C-terminal parts
      of human ZP4 may be relevant for its biological activity.

PMID- 22860759
TI  - Incidence, nature, and etiology of metabolic acidosis in dogs and cats.
AB  - BACKGROUND: Metabolic acidosis is an important abnormality in ill and injured
      dogs and cats. OBJECTIVES: To describe the incidence, nature, and etiology of
      metabolic acidosis in dogs and cats that had arterial or venous blood gases
      measured for any reason at a university teaching hospital. ANIMALS: Dogs and cats
      at the Veterinary Medical Teaching Hospital. METHODS: Acid base parameters and
      electrolyte and lactate concentrations in dogs and cats measured during a 13
      month period were retrospectively retrieved from a computer database. Metabolic
      acidosis was defined as a standardized base excess (SBE) in dogs of <-4 mmol/L
      and in cats <-5 mmol/L. RESULTS: A total of 1,805 dogs and cats were included; of
      these, 887 (49%) were classified as having a metabolic acidosis (753 dogs and 134
      cats). Primary metabolic acidosis was the most common disorder in dogs, whereas
      mixed acid base disorder of metabolic acidosis and respiratory acidosis was most
      common in cats. Hyperchloremic metabolic acidosis was more common than a high
      anion gap (AG) metabolic acidosis; 25% of dogs and 34% of cats could not be
      classified as having either a hyperchloremic metabolic acidosis or a high AG
      metabolic acidosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Metabolic acidosis was
      found commonly in this patient population and was associated with a wide variety
      of disease processes. Mixed acid base disorders occur frequently and routine
      categorization of metabolic acidosis based on the presence of high AG or
      hyperchloremia may be misleading in a large proportion of cases.

PMID- 22860760
TI  - The relative importance of donor age in deceased and living donor kidney
      transplantation.
AB  - In deceased donor kidney transplantation donor age is known to influence graft
      survival. The influence of living donor age on graft survival is questioned. We
      compared the influence of living and deceased donor age on the outcome of renal
      transplantation. All 1821 transplants performed in our center between 1990 and
      2009 were included in the analysis. Observation was until April 2012. A total of
      941 patients received a deceased donor kidney and 880 a living donor kidney. In
      multivariate Cox analysis, recipient age, maximum and current panel reactive
      antibodies, transplant year, HLA-mismatches, donor age, donor gender, donor type,
      delayed graft function, and calcineurin inhibitor (CNI) and prednisone as initial
      immunosuppression were found to have a significant influence on death-censored
      graft failure. The influence of both living and deceased donor age followed a J
      shaped curve, above 30 years the risk increased with increasing age. Donor type
      and donor age had an independent influence. The graft failure risk of deceased
      donor transplantation is almost twice that of living donor transplantation so
      that a 60-year-old living donor kidney has the same graft failure risk as a 20
      year-old deceased donor kidney.

PMID- 22860761
TI  - Carboranedithiols: building blocks for self-assembled monolayers on copper
      surfaces.
AB  - Two different positional isomers of 1,2-dicarba-closo-dodecaboranedithiols, 1,2
      (HS)(2)-1,2-C(2)B(10)H(10) (1) and 9,12-(HS)(2)-1,2-C(2)B(10)H(10) (2), have been
      investigated as cluster building blocks for self-assembled monolayers (SAMs) on
      copper surfaces. These two isomers represent a convenient system in which the
      attachment of SH groups at different positions on the skeleton affects their
      acidic character and thus also determines their reactivity with a copper surface.
      Isomer 1 exhibited etching of polycrystalline Cu films, and a detailed
      investigation of the experimental conditions showed that both the acidic
      character of SH groups and the presence of oxygen at the copper surface play
      crucial roles in how the surface reaction proceeds: whether toward a self
      assembled monolayer or toward copper film etching. We found that each positional
      isomer requires completely different conditions for the preparation of a SAM on
      copper surfaces. Optimized conditions for the former isomer required the exposure
      of a freshly prepared Cu surface to vapor of 1 in vacuum, which avoided the
      presence of oxygen and moisture. Adsorption from a dichloromethane solution
      afforded a sparsely covered Cu(0) surface; isomer 1 effectively removes the
      surface copper(I) oxide, forming a soluble product, but apparently binds only
      weakly to the clean Cu(0) surface. In contrast, adsorption of the latter, less
      volatile isomer proceeded better from a dichloromethane solution than from the
      vapor phase. Isomer 2 was even able to densely cover the copper surface cleaned
      up by the dichloromethane solution of 1. Both isomers exhibited high capacity to
      remove oxygen atoms from the surface copper(I) oxide that forms immediately after
      the exposure of freshly prepared copper films to ambient atmosphere. Isomer 2
      showed suppression of Cu film oxidation. A number of methods including X-ray
      photoelectron spectroscopy (XPS), X-ray Rutherford back scattering (RBS), proton
      induced X-ray emission (PIXE) analysis, atomic force microscopy (AFM), cyclic
      voltammetry, and contact angle measurements were used to investigate the
      experimental conditions for the preparation of SAMs of both positional isomers on
      copper surfaces and to shed light on the interaction between these molecules and
      a polycrystalline copper surface.

PMID- 22860762
TI  - Atom-transfer cyclization with CuSO4/KBH4: a formal "activators generated by
      electron transfer" process also applicable to atom-transfer polymerization.
AB  - The 4-exo and 5-exo-trig atom-transfer cyclizations of 1, 8a-e, 9, 12, and 13 can
      be mediated with as little as 0.05 mol % of Cu(TPMA)SO(4).5H(2)O in the presence
      of 2.5 mol % of borohydride salts in 10 min at room temperature in air. This
      formal "activators generated by electron transfer" (AGET) procedure utilizes a
      cheap and oxidatively stable copper source (CuSO(4).5H(2)O) and can be carried
      out in environmentally benign solvents (EtOH). It is possible to alter the
      product distribution in the 5-endo radical-polar crossover reactions of 10a,b and
      11 by tailoring the amount of borohydride. Cyclization onto alkynes 14 and 15 is
      also possible in only 20 min. Controlled radical polymerization of styrene, with
      increased rates over conventional atom-transfer radical polymerization (ATRP),
      can be carried out in a controlled fashion (Mn, PDI) using either CuBr or
      CuSO(4).5H(2)O and Bu(4)NBH(4).

PMID- 22860763
TI  - Competition between ascorbate and glutathione for the oxidized form of methylated
      quercetin metabolites and analogues: tamarixetin, 4'O-methylquercetin, has the
      lowest thiol reactivity.
AB  - Quercetin (Q) is a bioactive compound with excellent antioxidant activity.
      However, the thiol reactivity of its oxidation product (oxQ) forms a
      disadvantage. The aim of the present study was to decrease this thiol toxicity.
      We found that methylated Q metabolites displayed lower thiol reactivity than Q.
      The most effective was tamarixetin, 4'O-methylquercetin (4'MQ), that has a
      corresponding oxidation product (ox4'MQ) with thiol reactivity 350 times lower
      than oxQ. The endogenous metabolism of Q to 4'MQ might be a physiological way to
      safely benefit from the antioxidant potential of Q in vivo. Our results were
      explained with Pearson's HSAB concept and corroborated by quantum molecular
      calculations that revealed a strong correlation between the relative thiol
      reactivity and the lowest unoccupied molecular orbital (LUMO). The polarity of
      the molecule and the pi-pi interaction between the AC- and the B-ring appeared to
      determine the LUMO and the thiol reactivity of the oxidation product.

PMID- 22860764
TI  - Partial symptom-response to proton pump inhibitors in patients with non-erosive
      reflux disease or reflux oesophagitis - a post hoc analysis of 5796 patients.
AB  - BACKGROUND: Although most patients with gastro-oesophageal reflux disease (GERD)
      benefit from proton pump inhibitor (PPI) therapy, some experience only partial
      symptom relief. AIM: To determine the prevalence of partial heartburn response to
      PPIs and its impact on health-related quality of life. METHODS: Four randomised,
      double-blind studies in adults with reflux disease compared esomeprazole 40
      mg/day or 20 mg/day with omeprazole 20 mg/day, or esomeprazole 40 mg/day with
      pantoprazole 40 mg/day. Patients with heartburn on >=4 days during the 1-week
      recall period at baseline were included. Partial response was defined as
      heartburn on >=3 days during the last treatment week and reduced heartburn
      frequency after 4 weeks of treatment compared with baseline. RESULTS: The
      analysis included 2645 patients with non-erosive reflux disease (mean age: 48.8
      years; 54.4% women) and 3151 patients with reflux oesophagitis (mean age: 50.6
      years; 37.1% women). At baseline, most patients reported heartburn on 5-7 days
      (non-erosive reflux disease: 82.2%; reflux oesophagitis: 86.8%). Partial
      heartburn response occurred in 19.9% of patients with non-erosive reflux disease
      and 14.0% with reflux oesophagitis. Defining partial response as heartburn on >=2
      days increased these rates to 26.2% and 19.3%, respectively; defining partial
      response as heartburn of moderate or severe intensity on >=3 days decreased these
      rates to 6.4% and 5.3%, respectively. Nonresponse to PPIs was rare (non-erosive
      reflux disease: 2.4%; reflux oesophagitis: 1.4%). CONCLUSION: Using our
      conservative definition, partial heartburn response to proton pump inhibitor
      therapy occurred in 14-20% of gastro-oesophageal reflux disease patients, more
      commonly in non-erosive reflux disease than in reflux oesophagitis.

PMID- 22860765
TI  - Innovations in bioadhesive vaginal drug delivery system.
AB  - INTRODUCTION: Vagina, due to its anatomical position and physiological
      characteristics is increasingly being explored as a site for drug delivery in
      recent years. This route coupled with bioadhesion phenomena has born fruitful
      results in delivering drugs both locally as well as systemically. AREAS COVERED:
      Bioadhesive vaginal drug delivery system has been used for the treatment of local
      diseases affecting the vagina like candidiasis, STD, vaginal dryness, and so on.
      Also, research has demonstrated that drugs can be successfully delivered to
      systemic circulation via vaginal mucosa for treatment of various diseases like
      migraine and osteoporosis. Besides, this vaginal route has also been used for
      uterine targeting of drugs. This review focuses on these recent innovations that
      have been patented in the area of bioadhesive vaginal drug delivery systems. The
      review also highlights certain physicochemical characteristics of bioadhesive
      polymers that affect drug delivery through this route. EXPERT OPINION: An in
      depth study of this review will give an insight into the potential areas that can
      be explored while designing a bioadhesive vaginal drug delivery system. Also, the
      in vitro and in vivo experimental results discussed in the review will help
      stimulate research in development and optimization of newer formulations.

PMID- 22860766
TI  - Fatty acid synthase regulates proliferation and migration of colorectal cancer
      cells via HER2-PI3K/Akt signaling pathway.
AB  - Recent evidence suggests that fatty acid synthase mediating de novo fatty acid
      synthesis plays a crucial role in the carcinogenesis process of various cancers.
      Moreover, HER2 and related PI3K/Akt signaling pathway, which links intimately
      with cellular metabolism, influence cancer biological behavior. However, it
      remains unknown whether malignant phenotype of colorectal cancer cells is
      regulated by the HER2-PI3K/Akt-FASN signaling pathway. In this study, Caco-2
      cells were selected for functional characterization, and treated with ZSTK474,
      followed by RT-qPCR and Western blot assays examining PI3K, Akt, HER2, and FASN
      expression. The MTT and colony formation assays were used to assess
      proliferation. The migration was investigated by transwell, apoptosis, and cell
      cycle analysis. We found that the blockade of PI3K/Akt signaling pathway by
      ZSTK474 treatment led to downregulation of PI3K, Akt, HER2, and FASN expression.
      The proliferation was decreased upon treatment which was consistent with an
      increased percentage of G(1) arrested cells instead of apoptosis. The migration
      of Caco-2 cells was also impaired by ZSTK474 treatment. Inhibition of HER2
      PI3K/Akt signaling pathway suppresses FASN expression of Caco-2 cells, and
      inhibition of FASN expression changes malignant phenotype of Caco-2 cells.

PMID- 22860768
TI  - Depression: is pregnancy protective?

PMID- 22860767
TI  - Effects of altered alpha- and beta-branch carotenoid biosynthesis on
      photoprotection and whole-plant acclimation of Arabidopsis to photo-oxidative
      stress.
AB  - Functions of alpha- and beta-branch carotenoids in whole-plant acclimation to
      photo-oxidative stress were studied in Arabidopsis thaliana wild-type (wt) and
      carotenoid mutants, lutein deficient (lut2, lut5), non-photochemical quenching1
      (npq1) and suppressor of zeaxanthin-less1 (szl1) npq1 double mutant. Photo
      oxidative stress was applied by exposing plants to sunflecks. The sunflecks
      caused reduction of chlorophyll content in all plants, but more severely in those
      having high alpha- to beta-branch carotenoid composition (alpha/beta-ratio)
      (lut5, szl1npq1). While this did not alter carotenoid composition in wt or lut2,
      which accumulates only beta-branch carotenoids, increased xanthophyll levels were
      found in the mutants with high alpha/beta-ratios (lut5, szl1npq1) or without
      xanthophyll-cycle operation (npq1, szl1npq1). The PsbS protein content increased
      in all sunfleck plants but lut2. These changes were accompanied by no change
      (npq1, szl1npq1) or enhanced capacity (wt, lut5) of NPQ. Leaf mass per area
      increased in lut2, but decreased in wt and lut5 that showed increased NPQ. The
      sunflecks decelerated primary root growth in wt and npq1 having normal alpha/beta
      ratios, but suppressed lateral root formation in lut5 and szl1npq1 having high
      alpha/beta-ratios. The results highlight the importance of proper regulation of
      the alpha- and beta-branch carotenoid pathways for whole-plant acclimation, not
      only leaf photoprotection, under photo-oxidative stress.

PMID- 22860769
TI  - The intersection of progress and missed opportunities: provider group variations
      in chlamydia screening practices within California's Family Planning, Access,
      Care, and Treatment Program.

PMID- 22860770
TI  - Correlates of human papillomavirus vaccination rates in low-income, minority
      adolescents: a multicenter study.
AB  - BACKGROUND: Low rates of human papillomavirus (HPV) vaccination in low-income,
      minority adolescents may exacerbate racial disparities in cervical cancer
      incidence. METHODS: Using electronic medical record data and chart abstraction,
      we examined correlates of HPV vaccine series initiation and completion among 7702
      low-income and minority adolescents aged 11-21 receiving primary care at one of
      seven medical centers between May 1, 2007, and June 30, 2009. Our population
      included 61% African Americans, 13% Caucasians, 15% Latinas, and 11% other races;
      90% receive public insurance (e.g., Medicaid). We used logistic regression to
      estimate the associations between vaccine initiation and completion and age,
      race/ethnicity, number of contacts with the healthcare system, provider
      documentation, and clinical site of care. RESULTS: Of the 41% of adolescent girls
      who initiated HPV vaccination, 20% completed the series. A higher proportion of
      girls aged 11-<13 (46%) and 13-<18 (47%) initiated vaccination than those aged 18
      21 (28%). In adjusted analyses, receipt of other recommended adolescent vaccines
      was associated with vaccine initiation, and increased contact with the medical
      system was associated with both initiation and completion of the series.
      Conversely, provider failure to document risky health behaviors predicted
      nonvaccination. Manual review of a subset of unvaccinated patients' charts
      revealed no documentation of vaccine discussions in 67% of cases. CONCLUSIONS:
      Fewer than half of low-income and minority adolescents receiving health
      maintenance services initiated HPV vaccination, and only 20% completed the
      series. Provider failure to discuss vaccination with their patients appears to be
      an important contributor to nonvaccination. Future research should focus on
      improving both initiation and completion of HPV vaccination in high-risk
      adolescents.

PMID- 22860772
TI  - What influences clinical decision making?

PMID- 22860771
TI  - Fluorescence-on response via CB7 binding to viologen-dye pseudorotaxanes.
AB  - Fluorescence-on sensors typically rely on disrupting photoinduced electron
      transfer quenching of the excited state through binding the electron donor. To
      provide a more general fluorescence-on signaling unit, a quencher-fluorophore
      dyad has been developed in which quenching by electron transfer to a tethered
      viologen acceptor can be disrupted through complexation of the viologen by
      cucurbit[7]uril (CB7). Dyads of benzyl viologen-rhodamine B or a BODIPY
      fluorophore gave upon CB7 complexation 14- and 30-fold fluorescence enhancement,
      respectively.

PMID- 22860773
TI  - The role of statin therapy in patients with lower vascular risk.

PMID- 22860774
TI  - Funding of new cardiac technologies in Australia.

PMID- 22860775
TI  - The future of acute rheumatic fever and rheumatic heart disease in Australia.

PMID- 22860778
TI  - The ethics of industry sponsorship of charities.

PMID- 22860779
TI  - Measuring performance and outcomes of acute coronary syndromes management in
      Australia.

PMID- 22860780
TI  - Importance of ambulatory blood pressure in hypertension management.

PMID- 22860781
TI  - Is the non-medical use of prescription stimulants a problem in Australia?

PMID- 22860782
TI  - Does it take too long to become a doctor?

PMID- 22860783
TI  - Headache sufferers need to be heard too.

PMID- 22860784
TI  - The need to tackle concussion in Australian football codes.

PMID- 22860785
TI  - No more excuses: fracture liaison services work and are cost-effective.

PMID- 22860786
TI  - Nutrition competencies for the prevention and treatment of disease in Australian
      medical courses.

PMID- 22860787
TI  - Emergency department overcrowding and mortality after the introduction of the 4
      hour rule in Western Australia.

PMID- 22860788
TI  - Allergy to topical and oral goat products.

PMID- 22860789
TI  - Testing the golden rules of infectious diseases: staphylococcal bacteriuria is
      predictive of staphylococcal bacteraemia.

PMID- 22860790
TI  - Opportunistic serological surveillance for Murray Valley encephalitis virus in
      Victoria, February-May 2011.

PMID- 22860791
TI  - Terson syndrome: the need for fundoscopy in subarachnoid haemorrhage.

PMID- 22860792
TI  - Congenital heart disease: current knowledge about causes and inheritance.
AB  - About 80% of congenital heart disease (CHD) is multifactorial and arises through
      various combinations of genetic and environmental contributors. About 20% of
      cases can be attributed to chromosomal anomalies, Mendelian syndromes, non
      syndromal single gene disorders or teratogens. Down syndrome and velocardiofacial
      syndrome are the most commonly seen syndromes in patients with CHD. To date, more
      than 30 genes have been linked to non-syndromal forms of CHD. Their contribution
      to CHD remains unknown but is presumed to be relatively small. There is limited
      evidence for the contribution of specific environmental factors to CHD causation.
      However, folic acid supplementation in the pre- and peri-conception period,
      ensuring rubella vaccination has been completed before pregnancy, and maintaining
      good glycaemic control in mothers with diabetes may reduce the risk of CHD in
      infants. Recurrence risks vary between different types of non-syndromal CHD with
      multifactorial inheritance, and can be as high as 10% when two or more siblings
      are affected. Generally, the recurrence risk increases if a parent rather than a
      sibling is affected, particularly when the affected parent is the mother.
      Individualised recurrence risks can be generated for members of families affected
      by CHD after obtaining a detailed family history, including accurate cardiac
      diagnoses for all affected members. High-throughput genetic techniques can
      accelerate gene discovery and improve our ability to provide individualised
      genetic counselling.

PMID- 22860793
TI  - The effect of clinical history on accuracy of electrocardiograph interpretation
      among doctors working in emergency departments.
AB  - OBJECTIVE: To investigate whether bias in clinical history affects accuracy of
      electrocardiograph (ECG) interpretation among doctors working in emergency
      departments. DESIGN AND SETTING: Observational study conducted at four teaching
      hospitals in Sydney from May to September 2011. PARTICIPANTS: Participants
      interpreted 30 ECGs representing 10 diagnoses. ECGs were provided with positively
      biased history (suggestive of the correct diagnosis), negatively biased history
      (suggestive of an alternative diagnosis) or no history. MAIN OUTCOME MEASURES:
      Accuracy of ECG interpretation, measured as a score out of 10 (for each category
      of clinical history) and as a percentage of correctly interpreted ECGs. RESULTS:
      Of 307 doctors who were sent a recruitment email for the study, 132 participated
      (43%). The overall mean accuracy of ECG interpretation was 52% (95% CI, 50%-53%).
      For junior doctors, mean accuracy was 42% (95% CI, 40%-44%); for senior doctors,
      it was 65% (95% CI, 62%-67%). In adjusted models, the mean predicted score for
      senior doctors provided with no history was 6.25 (95% CI, 5.90-6.62) with junior
      doctors obtaining mean scores 34% lower than senior doctors (95% CI, 29%-40%; P <
      0.001). Compared with no history, positively biased history was associated with
      42% higher mean scores (95% CI, 35%-49%; P < 0.001) and negatively biased history
      was associated with 34% lower mean scores (95% CI, 29%-39%; P < 0.001).
      CONCLUSION: Bias in clinical history significantly influenced the accuracy of ECG
      interpretation. Strategies that reduce the detrimental impact of cognitive bias
      and improved ECG training for doctors are recommended.

PMID- 22860794
TI  - Single-centre experience of donation after cardiac death.
AB  - OBJECTIVES: To describe the design, development and implementation of an organ
      and tissue donation after cardiac death (DCD) program, evaluate its success and
      assess its impact on tissue and organ availability and the number of donors after
      brain death. DESIGN, PARTICIPANTS AND SETTING: Prospective collection of patient
      characteristics and outcomes for actual and potential donors from 2000 to 2010,
      thus including the 5 years after the implementation of a DCD program at a major
      Australian tertiary hospital in 2006. MAIN OUTCOME MEASURES: The number and type
      of donors before and after implementation of the DCD program, and subsequent
      numbers of solid organ and tissue donations. RESULTS: The DCD program was
      associated with an increase in overall donor numbers. There were 80 donors (20
      DCD and 60 donation after brain death [DBrD]) after 2006, compared with 51 DBrD
      donors in the previous 5 years. Four of the DBrD donors were patients who were
      initially considered for DCD. DCD accounted for eight of the total 19 donors in
      2009 and seven of the total 23 donors in 2010. There were 62 solid organ and 35
      tissue and cornea transplants as a result of the DCD program. CONCLUSIONS:
      Successful implementation of a DCD program is possible and has led to an increase
      in overall donor numbers and organs transplanted without any reduction in DBrD
      donors. The widespread implementation of DCD across Australia may help reduce the
      shortfall of organs for transplantation.

PMID- 22860795
TI  - Better Outcomes or Better Access -- which was better for mental health care?
AB  - OBJECTIVE: To compare the Better Access to Psychiatrists, Psychologists and
      General Practitioners through the MBS initiative with the Better Outcomes in
      Mental Health Care initiative, to test contentions that Better Access is used
      more often by advantaged major city patients and that the role of GPs has been
      reduced to that of referrers. DESIGN AND SETTING: Analysis of Bettering the
      Evaluation and Care of Health data relating to management of depression from
      April 1998 to March 2011, with the Better Outcomes period defined as January 2002
      to October 2006 and the Better Access period defined as November 2006 to December
      2011. MAIN OUTCOME MEASURES: Rates of depression management by GPs, including
      rates of mental health care item claims, referrals, prescribing and counselling,
      by patient location and socioeconomic group. RESULTS: During the study period,
      rates of depression management increased and rates of referrals to psychiatrists
      halved. Compared with Better Outcomes, Better Access resulted in: increased
      depression management for advantaged major city and disadvantaged non-major city
      patients (16.0% and 21.5% increases, respectively); a small decrease in
      prescribing for advantaged major city patients; decreases in GP counselling;
      increases in referrals to psychologists for all patient groups (three- to
      fourfold increases), with advantaged major city patients referred more often than
      patients in other groups; and increases in mental health care item claims for all
      patient groups (44-65-fold increases), with more claims for advantaged major city
      patients than both non-major city patient groups. CONCLUSION: Far from becoming
      "glorified referrers", GPs remain heavily involved in the management of
      depression. Better Access brought about an enormous increase in access to primary
      care management of depression, although advantaged major city patients gained
      most. Any changes to the system must not compromise the strong improvements in
      access that have occurred for all groups.

PMID- 22860796
TI  - Tiger snake (Notechis spp) envenoming: Australian Snakebite Project (ASP-13).
AB  - OBJECTIVES: To describe the clinical syndrome associated with definite tiger
      snake (Notechis spp) envenoming and to examine the ability of tiger snake
      antivenom (TSAV) to bind free venom in vivo. DESIGN, SETTING AND PARTICIPANTS: We
      conducted a prospective cohort study within the Australian Snakebite Project,
      reviewing all definite tiger snake envenoming cases between October 2004 and June
      2011. Definite cases were identified by venom-specific enzyme immunoassay or
      expert snake identification. MAIN OUTCOME MEASURES: Clinical effects of tiger
      snake envenoming; peak venom concentrations; number of vials of antivenom
      administered. RESULTS: Fifty-six definite tiger snake envenomings were
      identified. Clinical effects included venom-induced consumption coagulopathy
      (VICC) (n = 53), systemic symptoms (n = 45), myotoxicity (n = 11) and
      neurotoxicity (n = 17). Thrombotic microangiopathy occurred in three patients,
      all of whom developed acute renal failure. There were no deaths. A bite-site
      snake venom detection kit test was done in 44 patients, but was positive for
      tiger snake in only 33 cases. Fifty-three patients received TSAV and eight of
      these patients had immediate hypersensitivity reactions, severe enough in one
      case to satisfy diagnostic criteria for severe anaphylaxis. The median peak venom
      concentration in 50 patients with pretreatment blood samples available was 3.2
      ng/mL (interquartile range [IQR], 1-12 ng/mL; range 0.17-152 ng/mL). In 49
      patients with post-treatment blood samples available, no venom was detected in
      serum after the first antivenom dose. Ten patients were given 1 vial of TSAV; the
      median dose was 2 vials (range, 1-4 vials). Pretreatment serum venom
      concentrations did not vary significantly between patients given 1 vial of TSAV
      and those given 2 or more vials. CONCLUSION: Tiger snake envenoming causes VICC,
      systemic symptoms, neurotoxicity and myotoxicity. One vial of TSAV, the dose
      originally recommended when the antivenom was first made available, appears to be
      sufficient to bind all circulating venom.

PMID- 22860797
TI  - A multicentre evaluation of two intensive care unit triage protocols for use in
      an influenza pandemic.
AB  - OBJECTIVE: To determine the increase in intensive care unit (ICU) bed
      availability that would result from the use of the New South Wales and Ontario
      Health Plan for an Influenza Pandemic (OHPIP) triage protocols. DESIGN, SETTING
      AND PATIENTS: Prospective evaluation study conducted in eight Australian, adult,
      general ICUs, between September 2009 and May 2010. All patients who were admitted
      to the ICU, excluding those who had elective surgery, were prospectively
      evaluated using the two triage protocols, simulating a pandemic situation. Both
      protocols were originally developed to determine which patients should be
      excluded from accessing ICU resources during an influenza pandemic. MAIN OUTCOME
      MEASURE: Increase in ICU bed availability. RESULTS: At admission, the increases
      in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage protocol were
      3.5%, 14.7% and 22.7%, respectively, and 52.8% using the OHPIP triage protocol (P
      < 0.001). Re-evaluation of patients at 12 hours after admission using Tiers 1, 2
      and 3 of the NSW triage protocol incrementally increased ICU bed availability by
      19.2%, 16.1% and 14.1%, respectively (P < 0.001). The maximal cumulative
      increases in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage
      protocol were 23.7%, 31.6% and 37.5%, respectively, at 72 hours (P < 0.001), and
      65.0% using the OHPIP triage protocol, at 120 hours (P < 0.001). CONCLUSION: Both
      triage protocols resulted in increases in ICU bed availability, but the OHPIP
      protocol provided the greatest increase overall. With the NSW triage protocol,
      ICU bed availability increased as the protocol was escalated.

PMID- 22860798
TI  - The Australian Medical Association at 50 years.

PMID- 22860801
TI  - Sir Keith Stephen Jones MB BS(Hons), FRCS, FRACS, FACEM, FRACGP.

PMID- 22860802
TI  - Controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerization of AB-type
      monomers with PhPd(t-Bu3P)I or Pd2(dba)3/t-Bu3P/ArI as the initiator.
AB  - Controlled Pd(0)/t-Bu(3)P-catalyzed Suzuki cross-coupling polymerizations of AB
      type monomers via the chain-growth mechanism with an ArPd(t-Bu(3)P)I complex as
      the initiator are described. ArPd(t-Bu(3)P)I complexes, either prepurified or
      generated in situ from Pd(2)(dba)(3)/t-Bu(3)P/ArI (dba = dibenzylideneacetone)
      without separation/purification, were found to be efficient initiators in general
      for the controlled Suzuki cross-coupling polymerization, with narrow
      polydispersity indexes (PDIs) of 1.13-1.35 being observed. The Pd(2)(dba)(3)/t
      Bu(3)P/p-BrC(6)H(4)I combination was identified as a highly robust initiator
      system, with PDIs of <=1.20 in general and as low as 1.13 being obtained. Higher
      number-average molecular weights (M(n)) were achieved without a significant
      increase in the PDI (from 1.14 for a polymer with a M(n) = 9500 to 1.20 for a
      polymer with M(n) = 31,400) by using a smaller amount of the Pd(2)(dba)(3)/t
      Bu(3)P/p-BrC(6)H(4)I initiator in the polymerization.

PMID- 22860803
TI  - Ligand-receptor interaction platforms and their applications for drug discovery.
AB  - INTRODUCTION: The study of drug-target interactions is essential for the
      understanding of biological processes and for the efforts to develop new
      therapeutic molecules. Increased ligand-binding assays have coincided with the
      advances in reagents, detection and instrumentation technologies, the expansion
      in therapeutic targets of interest, and the increasingly recognized importance of
      biochemical aspects of drug-target interactions in determining the clinical
      performance of drug molecules. Nowadays, ligand-binding assays can determine
      every aspect of many drug-target interactions. AREAS COVERED: Given that ligand
      target interactions are very diverse, the author has decided to focus on the
      binding of small molecules to protein targets. This article first reviews the key
      biochemical aspects of drug-target interactions, and then discusses the detection
      principles of various ligand-binding techniques in the context of their primary
      applications for drug discovery and development. EXPERT OPINION: Equilibrium
      binding affinity should not be used as a solo indicator for the in vivo
      pharmacology of drugs. The clinical relevance of drug-binding kinetics demands
      high throughput kinetics early in drug discovery. The dependence of ligand
      binding and function on the conformation of targets necessitates solution-based
      and whole cell-based ligand-binding assays. The increasing need to examine ligand
      binding at the proteome level, driven by the clinical importance of the
      polypharmacology of ligands, has started to make the structure-based in silico
      binding screen an indispensable technique for drug discovery and development.
      Integration of different ligand-binding assays is important to improve the
      efficiency of the drug discovery and development process.

PMID- 22860874
TI  - Modalities of infant-mother interaction in Japanese, Japanese American immigrant,
      and European American dyads.
AB  - Cultural variation in relations and moment-to-moment contingencies of infant
      mother person-oriented and object-oriented interactions were compared in 118
      Japanese, Japanese American immigrant, and European American dyads with 5.5-month
      olds. Infant and mother person-oriented behaviors were related in all cultural
      groups, but infant and mother object-oriented behaviors were related only among
      European Americans. Infant and mother behaviors within each modality were
      mutually contingent in all groups. Culture moderated lead-lag relations: Japanese
      infants were more likely than their mothers to respond in object-oriented
      interactions; European American mothers were more likely than their infants to
      respond in person-oriented interactions. Japanese American dyads behaved like
      European American dyads. Interactions, infant effects, and parent socialization
      findings are set in cultural and accultural models of infant-mother transactions.

PMID- 22860875
TI  - Kinematic effects of a pedicle-lengthening osteotomy for the treatment of lumbar
      spinal stenosis.
AB  - OBJECT: Lumbar spinal stenosis (LSS) may lead to disabling neurogenic symptoms
      and has traditionally been treated using open laminectomy. A new technique for
      correcting LSS involves lengthening the lumbar pedicles through bilateral
      percutaneous pedicle osteotomies. In this paper, the authors' goal was to
      evaluate the changes in spinal canal dimensions and kinematic behavior after
      pedicle-lengthening osteotomies. METHODS: The kinematic behavior of 8 cadaveric
      lumbar segments was evaluated intact and after bilateral pedicle-lengthening
      osteotomies at the L-4, L-5, and L-4 and L-5 levels. Testing was conducted with
      and without a compressive preload using a custom kinematic apparatus that allowed
      for 3D tracking of each vertebra during flexion-extension, right-left bending,
      and right-left rotation. A validated finite element (FE) spine model was used to
      measure the changes in the cross-sectional area of the spinal canal and neural
      foramen after 2-, 3-, and 4.5-mm simulated pedicle-lengthening osteotomy
      procedures. RESULTS: The overall and segmental kinematics were not significantly
      altered after the pedicle-lengthening osteotomy procedure at the L-4 and/or L-5
      pedicles. The kinematic signatures of the intact and lengthened states were
      similar for all motion pairs. The FE spine model yielded kinematics predictions
      within or close to the 95% confidence interval for the cadaveric data. The FE
      spine demonstrated substantial, pedicle length-dependent enlargement of the cross
      sectional areas of the spinal canal and neural foramen after simulated pedicle
      lengthening. CONCLUSIONS: Bilateral pedicle-lengthening osteotomies produced
      substantial increases in the cross-sectional areas of the spinal canal and neural
      foramen without significantly altering normal spinal kinematics. This technique
      deserves further study as a less invasive treatment option for LSS.

PMID- 22860876
TI  - Three-dimensional motion of the uncovertebral joint during head rotation.
AB  - OBJECT: The uncovertebral joints are peculiar but clinically important anatomical
      structures of the cervical vertebrae. In the aged or degenerative cervical spine,
      osteophytes arising from an uncovertebral joint can cause cervical radiculopathy,
      often necessitating decompression surgery. Although these joints are believed to
      bear some relationship to head rotation, how the uncovertebral joints work during
      head rotation remains unclear. The purpose of this study is to elucidate 3D
      motion of the uncovertebral joints during head rotation. METHODS: Study
      participants were 10 healthy volunteers who underwent 3D MRI of the cervical
      spine in 11 positions during head rotation: neutral (0 degrees ) and 15 degrees 
      increments to maximal head rotation on each side (left and right). Relative
      motions of the cervical spine were calculated by automatically superimposing a
      segmented 3D MR image of the vertebra in the neutral position over images of each
      position using the volume registration method. The 3D intervertebral motions of
      all 10 volunteers were standardized, and the 3D motion of uncovertebral joints
      was visualized on animations using data for the standardized motion. Inferred
      contact areas of uncovertebral joints were also calculated using a proximity
      mapping technique. RESULTS: The 3D animation of uncovertebral joints during head
      rotation showed that the joints alternate between contact and separation.
      Inferred contact areas of uncovertebral joints were situated directly lateral at
      the middle cervical spine and dorsolateral at the lower cervical spine. With
      increasing angle of rotation, inferred contact areas increased in the middle
      cervical spine, whereas areas in the lower cervical spine slightly decreased.
      CONCLUSIONS: In this study, the 3D motions of uncovertebral joints during head
      rotation were depicted precisely for the first time.

PMID- 22860877
TI  - Spinal intradural myxoid chondrosarcoma.
AB  - The authors present a rare case of intradural extramedullary spinal
      chondrosarcoma. This 38-year-old man presented with urinary retention and lower
      limb weakness. Magnetic resonance imaging demonstrated a thoracic intradural
      extramedullary spinal tumor, which was resected. Histopathology revealed a
      meningeal myxoid chondrosarcoma. Despite adjuvant radiotherapy, the patient had
      multiple recurrences and metastases and died 18 months following his first
      surgery. The management of the rare entity of spinal canal chondrosarcoma is
      discussed.

PMID- 22860878
TI  - The impact of direct vertebral body derotation on the lumbar prominence in Lenke
      Type 5C curves.
AB  - OBJECT: The thoracic rib hump, caused by axial rotation of the spine, is one of
      the most dissatisfying cosmetic features associated with adolescent idiopathic
      scoliosis (AIS). However, advances in instrumentation and surgical techniques,
      such as direct vertebral body derotation (DVBD), have allowed improved correction
      in the axial plane and the rib hump. In cases of thoracolumbar/lumbar curves
      (Lenke Type 5), the lumbar prominence can be equally disfiguring and is often
      associated with waist asymmetry, another cosmetic concern. Although DVBD has been
      evaluated in the thoracic spine, little is known about its impact on the lumbar
      spine. The authors investigated the outcomes of DVBD on the lumbar prominence.
      METHODS: A prospectively collected multicenter database was queried for pediatric
      patients with AIS and Lenke Type 5 curves. All patients who underwent
      thoracoplasty procedures were excluded. A total of 34 patients underwent surgical
      correction via a posterior-only approach using pedicle screw constructs. Nineteen
      patients underwent concurrent DVBD, and the remaining 15 patients served as a
      control group and did not undergo DVBD. All patients had a minimum of 2 years of
      follow-up. RESULTS: The mean age of the entire cohort was 14.9 +/- 2.3 years, and
      the majority of patients were female (88%). All patients had Lenke Type 5C curves
      with a mean major curve of 46.0 degrees  +/- 8.7 degrees , which corrected to
      13.7 degrees  +/- 7.2 degrees  (70% correction). A mean of 10.7 +/- 3.0 levels
      were fused. Only thoracic kyphosis was significantly different between the groups
      preoperatively. Similarly, postoperative radiographic parameters were comparable
      between the groups, with equivalent percentages of correction. Although
      improvement in the thoracic rib hump was comparable between the groups, the DVBD
      group had 56.2% correction of the lumbar prominence, and the control group had
      76% improvement (p = 0.05). CONCLUSIONS: Although DVBD has been a valuable tool
      in the management of AIS, the authors' results suggest that its application for
      thoracolumbar curves may be limited. Further analysis with a larger cohort is
      required to better ascertain the impact of DVBD on thoracolumbar curves.

PMID- 22860879
TI  - Spontaneous improvement of cervical alignment after correction of global sagittal
      balance following pedicle subtraction osteotomy.
AB  - OBJECT: Sagittal spinopelvic malalignment is a significant cause of pain and
      disability in patients with adult spinal deformity. Surgical correction of
      spinopelvic malalignment can result in compensatory changes in spinal alignment
      outside of the fused spinal segments. These compensatory changes, termed
      reciprocal changes, have been defined for thoracic and lumbar regions but not for
      the cervical spine. The object of this study was to evaluate postoperative
      reciprocal changes within the cervical spine following lumbar pedicle subtraction
      osteotomy (PSO). METHODS: This was a multicenter retrospective radiographic
      analysis of patients from International Spine Study Group centers. Inclusion
      criteria were as follows: adults (>18 years old) with spinal deformity treated
      using lumbar PSO, a preoperative C7-S1 plumb line greater than 5 cm, and
      availability of pre- and postoperative full-length standing radiographs. RESULTS:
      Seventy-five patients (60 women, mean age 59 years) were included. The lumbar PSO
      significantly improved sagittal alignment, including the C7-S1 plumb line, C7-T12
      inclination, and pelvic tilt (p <0.001). After lumbar PSO, reciprocal changes
      were seen to occur in C2-7 cervical lordosis (from 30.8 degrees  to 21.6 degrees
      , p <0.001), C2-7 plumb line (from 27.0 mm to 22.9 mm), and T-1 slope (from -38.9
      degrees  to -30.4 degrees , p <0.001). Ideal correction of sagittal malalignment
      (postoperative sagittal vertical alignment < 50 mm) was associated with the
      greatest relaxation of cervical hyperlordosis (-12.4 degrees  vs -5.7 degrees , p
      = 0.037). A change in cervical lordosis correlated with changes in T-1 slope (r =
      -0.621, p <0.001), C7-T12 inclination (r = 0.418, p <0.001), T12-S1 angle (r = 
      0.339, p = 0.005), and C7-S1 plumb line (r = 0.289, p = 0.018). Radiographic
      parameters that correlated with changes in cervical lordosis on multivariate
      linear regression analysis included change in T-1 slope and change in C2-7 plumb
      line (r(2) = 0.53, p <0.001). CONCLUSIONS: Adults with positive sagittal
      spinopelvic malalignment compensate with abnormally increased cervical lordosis
      in an effort to maintain horizontal gaze. Surgical correction of sagittal
      malalignment results in improvement of the abnormal cervical hyperlordosis
      through reciprocal changes.

PMID- 22860880
TI  - X-ray crystallographic characterization of new soluble endohedral fullerenes
      utilizing the popular C82 bucky cage. Isolation and structural characterization
      of Sm@C3v(7)-C82, Sm@C(s)(6)-C82, and Sm@C2(5)-C82.
AB  - Three isomers of Sm@C(82) that are soluble in organic solvents were obtained from
      the carbon soot produced by vaporization of hollow carbon rods doped with
      Sm(2)O(3)/graphite powder in an electric arc. These isomers were numbered as
      Sm@C(82)(I), Sm@C(82)(II), and Sm@C(82)(III) in order of their elution times from
      HPLC chromatography on a Buckyprep column with toluene as the eluent. The
      identities of isomers, Sm@C(82)(I) as Sm@C(s)(6)-C(82), Sm@C(82)(II) as
      Sm@C(3v)(7)-C(82), and Sm@C(82)(III) as Sm@C(2)(5)-C(82), were determined by
      single-crystal X-ray diffraction on cocrystals formed with
      Ni(octaethylporphyrin). For endohedral fullerenes like La@C(82), which have three
      electrons transferred to the cage to produce the M(3+)@(C(82))(3-) electronic
      distribution, generally only two soluble isomers (e.g., La@C(2v)(9)-C(82) (major)
      and La@C(s)(6)-C(82) (minor)) are observed. In contrast, with samarium, which
      generates the M(2+)@(C(82))(2-) electronic distribution, five soluble isomers of
      Sm@C(82) have been detected, three in this study, the other two in two related
      prior studies. The structures of the four Sm@C(82) isomers that are currently
      established are Sm@C(2)(5)-C(82), Sm@C(s)(6)-C(82), Sm@C(3v)(7)-C(82), and
      Sm@C(2v)(9)-C(82). All of these isomers obey the isolated pentagon rule (IPR) and
      are sequentially interconvertable through Stone-Wales transformations.

PMID- 22860881
TI  - Self-reported dietary intake of potassium, calcium, and magnesium and risk of
      dementia in the Japanese: the Hisayama Study.
AB  - OBJECTIVES: To investigate whether higher intake of potassium, calcium, and
      magnesium reduces the risk of incident dementia. DESIGN: Prospective cohort
      study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: One thousand eighty
      one community-dwelling Japanese individuals without dementia aged 60 and older.
      MEASUREMENTS: A 70-item semiquantitative food frequency questionnaire was used to
      assess potassium, calcium, and magnesium intakes. Hazard ratios (HRs) for the
      development of all-cause dementia and its subtypes were estimated using Cox
      proportional hazards model. RESULTS: During a 17-year follow-up, 303 participants
      experienced all-cause dementia; of these, 98 had vascular dementia (VaD), and 166
      had Alzheimer's disease (AD). The multivariable-adjusted HRs for the development
      of all-cause dementia were 0.52 (95% confidence interval [CI] = 0.30-0.91), 0.64
      (95% CI = 0.41-1.00), and 0.63 (95% CI = 0.40-1.01) for the highest quartiles of
      potassium, calcium, and magnesium intake, respectively, compared with the
      corresponding lowest quartiles. Similarly, the HRs for the development of VaD
      were 0.20 (95% CI = 0.07-0.56), 0.24 (95% CI = 0.11-0.53), and 0.26 (95% CI =
      0.11-0.61) for the highest quartiles of potassium, calcium, and magnesium intake,
      respectively. There was no evidence of a linear association between these mineral
      intakes and the risk of AD. CONCLUSION: Higher self-reported dietary intakes of
      potassium, calcium, and magnesium reduce the risk of all-cause dementia,
      especially VaD, in the general Japanese population.

PMID- 22860882
TI  - Comparisons of high-dose and combination nicotine replacement therapy,
      varenicline, and bupropion for smoking cessation: a systematic review and
      multiple treatment meta-analysis.
AB  - AIM: This review compared the effect of high-dose nicotine replacement therapy
      (NRT) and combinations of NRT for increasing smoking abstinence rates compared to
      standard-dose NRT patch, varenicline, and bupropion on smoking abstinence.
      METHODS: Ten electronic databases were searched (up to January 2012) for
      randomized controlled trials (RCT) of standard-dose (<= 22 mg) or high-dose
      nicotine patch therapy (> 22 mg), combination NRT (e.g. nicotine patch + nicotine
      inhaler), bupropion, and varenicline. Analysis consisted of random-effects
      pairwise meta-analysis and a Bayesian multiple treatment comparison (MTC).
      RESULTS: We identified 146 RCTs (65 standard-doses of the nicotine patch (<= 22
      mg); 6 high-dose NRT patch (> 22 mg); 5 high versus standard-dose NRT patch; 5
      combination NRT versus inert controls; 6 combination versus single NRT patch; 48
      bupropion; and 11 varenicline). The MTC found that all therapies offered
      treatment benefits at most time points over controls. Combination NRT and higher
      dose NRT did not demonstrate consistent effects over other interventions. With
      the exception of varenicline, the benefits of treatments over standard-dose NRT
      were not retained in the long term. CONCLUSIONS: All pharmacologic treatments
      were significantly more effective than inert controls. Varenicline was the only
      treatment demonstrating effects over other options. These results should be
      considered in the development of clinical practice guidelines.

PMID- 22860883
TI  - Calcium and phosphate homeostasis in hyperthyroid cats: associations with
      development of azotaemia and survival time.
AB  - OBJECTIVES: To evaluate calcium and phosphate homeostasis in hyperthyroid cats
      and determine if plasma parathyroid hormone and fibroblast growth factor-23 are
      associated with the presence of -azotaemic chronic kidney disease and/or have
      prognostic significance. METHODS: Retrospective cohort study. Logistic regression
      analysis and Cox regression analysis were performed to identify if parathyroid
      hormone and fibroblast growth factor-23 were predictors of development of
      azotaemia following treatment and survival time, respectively. RESULTS: Two
      hundred and seven hyperthyroid cats were included. Elevated plasma parathyroid
      hormone concentrations, hyperphosphataemia, decreased plasma fibroblast growth
      factor-23 concentrations and hypocalcaemia were documented; however, all
      parameters returned to reference intervals following treatment of hyperthyroid
      cats without azotaemic chronic kidney disease. After adjustment for plasma
      creatinine concentration, baseline plasma parathyroid hormone and fibroblast
      growth factor-23 concentrations were not predictors of the development of
      azotaemia following treatment. Baseline plasma fibroblast growth factor-23
      concentrations were associated with all-cause mortality; however, this
      association was not maintained after adjustment for packed cell volume. CLINICAL
      SIGNIFICANCE: Changes in plasma parathyroid hormone and fibroblast growth factor
      23 concentrations which occur in hyperthyroid cats are not mediators of
      progression of chronic kidney disease; however, fibroblast growth factor-23 would
      appear to have some prognostic significance in hyperthyroidism.

PMID- 22860884
TI  - Can we trust the new generation of infrared tympanic thermometers in clinical
      practice?
AB  - AIMS AND OBJECTIVES: To explore the reliability and validity of the new
      generation of infrared tympanic thermometers, comparing with rectal and core
      temperature, and to decide their applicability to clinical practice. BACKGROUND:
      Digital contact thermometers for rectal measurements and infrared tympanic
      thermometers are the most common way to measure patients' temperature. Previous
      studies of the infrared tympanic thermometers revealed misdiagnosis, and validity
      of early models was questioned. DESIGN: Reliability and validity study. METHODS:
      Temperature was measured with two infrared tympanic thermometers brands in both
      ears and compared with rectal temperature twice a day at the ward (n = 200). At
      the intensive care unit, patients (n = 42) underwent the same measurement
      procedures every fourth hour for 24 hours. In addition, core temperature was
      measured. Statistical analyses included descriptive and mixed models analyses.
      RESULTS: Ward: Infrared tympanic thermometers measured the temperature lower than
      the rectal temperature. Descriptive statistics indicate higher variation in
      temperature measurements made in the ear. No statistically significant difference
      in temperature was found for left ear vs. right ear. Intensive care unit: The
      mean rectal temperature was higher than the mean core and ear temperature. Mixed
      models analyses of the temperatures at the ward and the intensive care unit
      showed the same overall trends, but with less discrepancy between the two
      infrared tympanic thermometers brands, compared with the rectal temperature. Only
      rectal temperature measurements differed significantly from the core temperature.
      CONCLUSION: Our study shows good reliability using the new generation of infrared
      tympanic thermometers. We found good agreement between core and infrared tympanic
      thermometers at the intensive care unit, but the measuring inaccuracy for
      infrared tympanic thermometers was greater than expected. RELEVANCE TO CLINICAL
      PRACTICE: The new generation of infrared tympanic thermometers may be used in
      clinical practice, but it is important to do repeatedly measurements if there is
      discrepancy between the temperature and the observation of the patient condition.

PMID- 22860885
TI  - Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX
      weighted daylight doses measured in six geographical locations.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma
      skin cancers and actinic keratoses (AKs). Daylight-mediated methyl
      aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure
      for PDT. All daylight-PDT studies have been performed in the Nordic countries. To
      be able to apply these results in other parts of the world we have to compare the
      daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light
      doses found in Nordic countries. OBJECTIVES:   To calculate where and when
      daylight-PDT of AKs was possible in six different geographical locations using
      ground stations measuring PpIX-weighted daylight doses. METHODS:   PpIX-weighted
      daylight doses were measured using a dosimeter with a customer-specific
      photodiode with a detector sensitivity that mimics the PpIX absorption spectrum
      and measures in 'PpIX doses'. The dosimeters were built into ground stations that
      were placed in six geographical locations measuring from July to December 2008.
      Temperature data for each location were obtained from the internet. The maximal
      ultraviolet (UV) index for Copenhagen was obtained for the measuring period of
      the dosimeters. RESULTS:   If the PpIX light dose should be above 8Jcm(-2) and
      the maximum temperature of the day at least 10 degrees C, it was possible to
      treat patients on nearly all days until the middle of September in Reykjavik and
      Oslo, until the last week of October in Copenhagen and Regensburg, until the
      middle of November in Turin and all year in Israel. CONCLUSIONS:   Where and when
      to perform daylight-PDT depends on the PpIX light dose and outdoor temperature.
      The PpIX light dose was influenced by the geographical location (latitude),
      weather condition and time of year. The UV index was not more suitable than
      temperature and weather to predict if the intensity of daylight would be
      sufficient for daylight-PDT.

PMID- 22860886
TI  - Pacemaker wire central venous stenosis and one more reason to not run central
      venous catheters for dialysis in reverse flow.
AB  - A 75-year-old man on chronic peritoneal dialysis had unrecognized stenosis of the
      superior vena cava (SVC) due to pacemaker wires placed 5 years earlier. The
      patient was placed on hemodialysis after hernia surgery. When a tunneled central
      venous catheter for dialysis was placed from the right internal jugular (IJ)
      vein, the venous lumen extended through the stenotic area but not the arterial
      lumen. Probably due to a subsequent clot at the arterial lumen port the patient
      developed SVC syndrome and when the catheter was run in the reversed flow
      direction he developed hypovolemic shock. The stenosis and SVC syndrome resolved
      with angioplasty of the SVC stenosis, removal of the IJ catheter and use of a
      femoral vein catheter. The patient eventually returned to peritoneal dialysis and
      the femoral catheter was removed.

PMID- 22860887
TI  - A collaborative, systems-level approach to eliminating healthcare-associated
      MRSA, central-line-associated bloodstream infections, ventilator-associated
      pneumonia, and respiratory virus infections.
AB  - To achieve sustainable reductions in healthcare-associated infections (HAIs), the
      University of Washington Medical Center (UWMC) deployed a collaborative, systems
      level initiative. With the sponsorship of senior leadership, multidisciplinary
      teams were established to address healthcare-associated methicillin-resistant
      Staphylococcus aureus (MRSA), central-line-associated bloodstream infections
      (CLABSI), ventilator-associated pneumonia (VAP), and respiratory virus
      infections. The goal of the initiative was to eliminate these four HAIs among
      medical center inpatients by 2012. In the first 24 months of the project, the
      number of healthcare-associated MRSA cases decreased 58%; CLABSI cases decreased
      54%. Staff and provider compliance with infection prevention measures improved
      and remained strong, for example, 96% compliance with hand hygiene, 98%
      compliance with the recommended influenza vaccination program, and 100%
      compliance with the VAP bundle. Achieving these results required an array of
      coordinated, systems-level interventions. Critical project success factors were
      believed to include creating organizational alignment by declaring eliminating
      HAIs as an organizational breakthrough goal, having the organization's executive
      leadership highly engaged in the project, coordination by an experienced and
      effective project leader and manager, collaboration by multidisciplinary project
      teams, and promoting transparency of results across the organization.

PMID- 22860888
TI  - Mechanical properties of poly(dimethylsiloxane)-block-poly(2-methyloxazoline)
      polymersomes probed by atomic force microscopy.
AB  - Poly(dimethylsiloxane)-block-poly(2-methyloxazoline) (PDMS-b-PMOXA) vesicles were
      characterized by a combination of dynamic light scattering (DLS), cryogenic
      transmission electron microscopy (cryo-TEM), and atomic force microscopy imaging
      and force spectroscopy (AFM). From DLS data, a hydrodynamic radius of ~150 nm was
      determined, and cryo-TEM micrographs revealed a bilayer thickness of ~16 nm. In
      AFM experiments on a silicon wafer substrate, adsorption led to a stable
      spherical caplike conformation of the polymersomes, whereas on mica, adsorption
      resulted also in vesicle fusion and formation of bilayer patches or multilayer
      stacks. This indicates a delicate balance between the mechanical stability of
      PDMS-b-PMOXA polymersomes on one hand and the driving forces for spreading on the
      other. A Young's modulus of 17 +/- 11 MPa and a bending modulus of 7 +/- 5 * 10(
      18) J were derived from AFM force spectroscopy measurements. Therefore, the
      elastic response of the PDMS-b-PMOXA polymersomes to external stimuli is much
      closer to that of lipid vesicles compared to other types of polymersomes, such as
      polystyrene-block-poly(acrylic acid) (PS-b-PAA).

PMID- 22860891
TI  - A method to quantify quinone reaction rates with wine relevant nucleophiles: a
      key to the understanding of oxidative loss of varietal thiols.
AB  - Quinones are key reactive electrophilic oxidation intermediates in wine. To
      address this question, the model 4-methyl-1,2-benzoquinone was prepared to study
      how it reacts with wine nucleophiles. Those investigated included the varietal
      volatile thiols 4-methyl-4-sulfanylpentan-2-one (4MSP), 3-sulfanylhexan-1-ol
      (3SH), and 2-furanmethanethiol (2FMT); hydrogen sulfide (H2S); glutathione (GSH);
      sulfur dioxide; ascorbic acid (AA); and the amino acids methionine (Met) and
      phenylalanine (Phe) in the first kinetic study of these reactions. Products were
      observed in fair to quantitative yields, but yields were negligible for the amino
      acids. The reaction rates of 4-methyl-1,2-benzoquinone toward the nucleophiles
      were quantified by UV-vis spectrometry monitoring the loss of the quinone
      chromophore. The observed reaction rates spanned three orders of magnitude, from
      the unreactive amino acids (Met and Phe) (KNu = 0.0002 s(-1)) to the most
      reactive nucleophile, hydrogen sulfide (KH2S = 0.4188 s(-1)). Analysis of the
      kinetic data showed three categories. The first group consisted of the amino
      acids (Met and Phe) having rates of essentially zero. Next, phloroglucinol has a
      low rate (KPhl = 0.0064 s(-1)). The next group of compounds includes the volatile
      thiols having increasing reactions rates K as steric inhibition declined (K4MSP =
      0.0060 s(-1), K3SH = 0.0578 s(-1), and K2FMT = 0.0837 s(-1)). These volatile
      thiols (4MSP, 3SH, 2FMT), important for varietal aromas, showed lower K values
      than those of the third group, the wine antioxidant compounds (SO2, GSH, AA) and
      H2S (KNu = 0.3343-0.4188 s(-1)). The characterization of the reaction products
      between the nucleophiles and 4-methyl-1,2-benzoquinone was performed by using
      HPLC with high-resolution MS analysis. This study presents the first evidence
      that the antioxidant compounds, H2S, and wine flavanols could react
      preferentially with oxidation-induced quinones under specific conditions,
      providing insight into a mechanism for their protective effect. 

PMID- 22860889
TI  - Fruit, vegetable, and animal food intake and breast cancer risk by hormone
      receptor status.
AB  - The effects of diet on breast cancer are controversial and whether the effects
      vary with hormone receptor status has not been well investigated. This study
      evaluated the associations of dietary factors with risk for breast cancer overall
      and by the hormone receptor status of tumors among Chinese women. The Shanghai
      Breast Cancer Study, a large, population-based, case-control study, enrolled
      3,443 cases and 3,474 controls in 1996-1998 (phase I) and 2002-2005 (phase II);
      2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data.
      Dietary intake was assessed using a validated, quantitative, food frequency
      questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      derived from multivariate, polychotomous, unconditional logistic regression
      models. Total vegetable intake was inversely related to breast cancer risk, with
      an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67-0.95; P trend =
      0.02). Reduced risk was also related to high intake of allium vegetables (P trend
      = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and
      rosaceae fruits were inversely associated with breast cancer risk (P trend =
      0.003 and 0.004, respectively), although no consistent association was seen for
      total fruit intake. Elevated risk was observed for all types of meat and fish
      intake (all P trend < 0.05), whereas intakes of eggs and milk were associated
      with a decreased risk of breast cancer (both P trend <0.05). There was little
      evidence that associations with dietary intakes varied across the 4 tumor
      subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our
      results suggest that high intake of total vegetables, certain fruits, milk, and
      eggs may reduce the risk of breast cancer, whereas high consumption of animal
      source foods may increase risk. The dietary associations did not appear to vary
      by ER/PR status.

PMID- 22860892
TI  - Novel pharmacological modulators of autophagy and therapeutic prospects.
AB  - INTRODUCTION: Autophagy is an intracellular process of self-digestion involving
      the lysosomal degradation of cytoplasmic organelles and macromolecules. It occurs
      at low basal levels to perform housekeeping functions and is dramatically
      augmented upon nutrient depletion or exposure to other stresses, thus maintaining
      cellular homeostasis and energy balance and providing cytoprotective responses to
      adverse conditions. Mounting evidence that autophagy malfunction contributes to
      the pathogenesis of diverse human diseases has stimulated efforts to identify
      pharmacological agents that modulate autophagy in potentially beneficial ways.
      Here, we review the progresses accomplished toward this goal in recent years, as
      reflected by the patent literature. AREAS COVERED: Patent applications published
      from 2008 to mid-2012 that pertain to the pharmacological modulation of autophagy
      are reviewed and their potential therapeutic utilities are discussed. EXPERT
      OPINION: Of 40 patents related to autophagy, 21 claim novel enhancers or
      inhibitors of autophagy. One of the most promising applications of these
      compounds concerns cancer therapy, a few of them being already considered for
      clinical evaluation. Further work is, however, needed to identify compounds that
      target unique molecular effectors/regulators of autophagy to selectively modulate
      its various stages in different tissues and to design therapeutic interventions
      applicable to a broad variety of dysfunctional autophagy-associated disorders.

PMID- 22860893
TI  - Interleukin-24 mediates apoptosis in human B-cells through early activation of
      cell cycle arrest followed by late induction of the mitochondrial apoptosis
      pathway.
AB  - Interleukin (IL)-24 has death-promoting effects on various proliferating cells
      including B-cells from chronic lymphocytic leukemia (CLL) and germinal center B
      cells, but its molecular mechanisms are poorly understood. Using a B-cell
      differentiation model and mRNA profiling, we found that recombinant (r)IL-24
      stimulated genes of the mitochondrial apoptotic pathway (Bax, Bid, Casp8, COX6C,
      COX7B) after 36 h, whereas the transcription of genes involved in DNA replication
      and metabolism was inhibited within 6 h. Unexpectedly, insulin-like growth factor
      1 (IGF1), a hormone known to promote cell growth, was stimulated by IL-24.
      Activated B-cells express receptor for IGF1, to which they become sensitized and
      undergo apoptosis, a mechanism similar in this respect to IL-24-induced cell
      death. Furthermore, inhibition of the IGF1 pathway reversed the effects of IL-24.
      IL-24-mediated apoptosis was also antagonized by pifithrin-alpha, an inhibitor of
      p53 transactivation. Altogether, these results disclose sequential molecular
      signals generated by IL-24 in activated B-cells.

PMID- 22860894
TI  - Genetic polymorphisms of tumour necrosis factor receptor superfamily 1b and fas
      ligand are associated with clinical efficacy and/or acute severe infusion
      reactions to infliximab in Crohn's disease.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in TNF receptor superfamily
      (TNFRSF) 1A and 1B, and Fas ligand (FASLG) genes, have been associated with
      responsiveness to infliximab (IFX) in Crohn's disease. AIM: To investigate if
      SNPs in TNFRSF1A and 1B, and FAS (TNFRSF6) and FASLG (TNFSF6), associated with
      short- or long-term clinical and biological efficacy and with acute severe
      infusion reactions. METHODS: Observational, retrospective and explorative cohort
      study of IFX-treated Caucasian patients with Crohn's disease classified as
      primary nonresponders (n = 21), response failures on maintenance therapy (n =
      37), maintained remission (n = 47) and occurrence of acute severe infusion
      reactions (n = 20). RESULTS: During IFX maintenance therapy, minor allele
      carriage of TNFRSF1B, rs976881 is associated with loss of response [OR 3.3 (1.2
      9.1), P = 0.014]. Minor allele homozygosity increased the risk substantially (OR
      estimated 19, P = 0.006), and furthermore associated with a mean CRP increase of
      17 mg/L as compared to a mean decrease of 17 mg/L in all others (P = 0.036). In
      contrast, minor allele carriage of TNFRSF1B, rs1061622 is associated with
      beneficial response to IFX induction [OR 4.2 (1.2-18.2), P = 0.014], and with
      persistence of remission during maintenance therapy [OR 5.5 (1.5-25.5), P =
      0.007]. Carriage of the minor allele of FASLG, rs76110 increased risk of severe
      infusion reactions [OR 4.0 (1.1-22.4), P = 0.041]; minor allele carriage of
      TNFRSF1B, rs652625 decreased the risk (OR estimated 0.2, P = 0.043 ).
      CONCLUSIONS: The TNFRSF1B polymorphisms may contribute to predict efficacy of
      infliximab. Moreover, FASLG and TNFRSF1B polymorphisms may confer genetic
      susceptibility to severe infusion reactions. These findings could potentially aid
      clinical decisions if confirmed in larger studies.

PMID- 22860895
TI  - Triplet excited state behavior of naphthalene-based pseudopeptides in the
      presence of energy donors.
AB  - In this work, the triplet state behavior of naphthalene-based pseudopeptides with
      amide-based macrocyclic or lateral chain substructures has been investigated in
      the presence of benzophenone and/or biphenyl, as suitable energy-donating
      chromophores. Their behavior has been compared with that of 1,4
      dimethylnaphthalene as model compound. In all the cases, the triplet-triplet
      absorption of naphthalene is detected by transient absorption spectroscopy, upon
      selective excitation of benzophenone at 355 nm. The kinetics of formation and
      decay of this species is markedly slower in the pseudopeptides, due to
      retardation of triplet-triplet energy transfer and exciplex formation. Finally,
      the delayed fluorescence detected in the model naphthalene is absent in the
      pseudopeptides. The concept can, in principle, be exploited for the study of
      excited-state interactions in supramolecular systems.

PMID- 22860896
TI  - High-throughput two-dimensional root system phenotyping platform facilitates
      genetic analysis of root growth and development.
AB  - High-throughput phenotyping of root systems requires a combination of specialized
      techniques and adaptable plant growth, root imaging and software tools. A custom
      phenotyping platform was designed to capture images of whole root systems, and
      novel software tools were developed to process and analyse these images. The
      platform and its components are adaptable to a wide range root phenotyping
      studies using diverse growth systems (hydroponics, paper pouches, gel and soil)
      involving several plant species, including, but not limited to, rice, maize,
      sorghum, tomato and Arabidopsis. The RootReader2D software tool is free and
      publicly available and was designed with both user-guided and automated features
      that increase flexibility and enhance efficiency when measuring root growth
      traits from specific roots or entire root systems during large-scale phenotyping
      studies. To demonstrate the unique capabilities and high-throughput capacity of
      this phenotyping platform for studying root systems, genome-wide association
      studies on rice (Oryza sativa) and maize (Zea mays) root growth were performed
      and root traits related to aluminium (Al) tolerance were analysed on the parents
      of the maize nested association mapping (NAM) population.

PMID- 22860897
TI  - Nanosize and surface charge effects of hydroxyapatite nanoparticles on red blood
      cell suspensions.
AB  - In this paper, the effects of size and surface charge of hydroxyapatite (HAP)
      particles on a red blood cell (RBC) suspension were studied. Results showed that
      the HAP particles exhibited nanosize and surface charge effects on the RBC
      suspension. Differing from HAP microparticles, HAP nanoparticles induced some
      aggregation of the RBCs in the unstructured agglutinates. HAP nanoparticles were
      adhered to the surface membrane of the RBCs due to their remarkably higher
      adsorption capacity than the HAP microparticles, resulting in the formation of a
      sunken appearance ("caves") on the surface membrane of the RBCs without rupturing
      the lipid bilayer. In the case of high negatively charged HAP nanoparticles after
      heparin modification, the aggregation of the RBCs induced by the HAP
      nanoparticles was inhibited. Such HAP nanoparticle-induced aggregation of the
      RBCs could be attributed to the bridging force via the electrostatic interaction
      between the positively charged binding sites on the HAP surface and the
      negatively charged groups on the surface of the RBCs. The surface charge of the
      HAP nanoparticles is thus a crucial factor influencing the interaction between
      the HAP nanoparticles and the RBCs.

PMID- 22860898
TI  - {1,6}-Transannular catalytic asymmetric Gosteli-Claisen rearrangement.
AB  - The first uncatalyzed and [Cu(R-box)L(2)](SbF(6))(2)-catalyzed {1,6}-transannular
      Gosteli-Claisen rearrangement of cyclic 2-alkoxycarbonyl-substituted allyl vinyl
      ethers to afford medium- and large-sized carbacycles is disclosed.

PMID- 22860899
TI  - Evaluation of two fatigability severity measures in elderly adults.
AB  - OBJECTIVES: To document the stability, concurrent validity, and clinical
      correlates of two fatigability severity measures as recommended by the American
      Geriatrics Society. DESIGN: Descriptive, cross-sectional. SETTING: Two
      independent living and one community senior centers. PARTICIPANTS: Forty-three
      participants, with an average age 85 +/- 6. MEASUREMENTS: Perceived fatigability
      severity was quantified by directly asking participants to report change in
      energy after a standardized 10-minute walk at a self-selected pace. Performance
      fatigability severity was defined as a ratio of change in walking speed to total
      distance walked. The walk test was repeated within 2 weeks to assess stability.
      Total daily physical activity (PA) was measured over 7 consecutive days using a
      waist-worn accelerometer. Frailty was measured using the Vulnerable Elders Survey
      interview scale, and gait speed was measured using a standardized 25-feet walk
      test. RESULTS: The perceived and performance fatigability severity measures were
      significantly correlated (correlation coefficient (r) = 0.94, P < .001) and
      stable over two assessments (r = 0.82 and 0.85, P < .001). Both fatigability
      severity measures were significantly correlated with PA level (r = -0.42 and r = 
      0.44, respectively, P = .02), frailty (r = 0.47 and 0.53, respectively, P = .001)
      and gait speed (r = -0.45, P = .003 and r = -0.54, P = .001, respectively).
      CONCLUSION: The methodology described in this study permits the calculation of
      two highly correlated fatigability severity scores, which summarize the
      relationship between a person's change in self-reported tiredness or change in
      physical performance and concurrently measured PA. The fatigability severity
      scores are reproducible and correlated with clinical measures predictive of
      decline. The methods used to quantify fatigability severity can be implemented
      during a brief assessment (<15 minutes) and should be useful in the design and
      evaluation of interventions to increase PA in older adults at risk of functional
      decline.

PMID- 22860901
TI  - Non-genetic mechanisms communicating antibiotic resistance: rethinking strategies
      for antimicrobial drug design.
AB  - INTRODUCTION: Infections by multidrug-resistant bacteria are of great concern
      worldwide. In many cases, resistance is not due to the presence of specific
      antibiotic-modifying enzymes, but rather associated with a general impermeability
      of the bacterial cell envelope. The molecular bases of this intrinsic resistance
      are not completely understood. Moreover, horizontal gene transfers cannot solely
      explain the spread of intrinsic resistance among bacterial strains. AREAS
      COVERED: This review focuses on the increased intrinsic antibiotic resistance
      mediated by small molecules. These small molecules can either be secreted from
      bacterial cells of the same or different species (e.g., indole, polyamines,
      ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial
      cell milieu, whether in the environment, such as indole acetic acid and other
      plant hormones, or in human tissues and body fluids, such as polyamines. These
      molecules are metabolic byproducts that act as infochemicals and modulate
      bacterial responses toward antibiotics leading to increasing or decreasing
      resistance levels. EXPERT OPINION: The non-genetic mechanisms of antibiotic
      response modulation and communication discussed in this review should reorient
      our thinking of the mechanisms of intrinsic resistance to antibiotics and its
      spread across bacterial cell populations. The identification of chemical signals
      mediating increased intrinsic antibiotic resistance will expose novel critical
      targets for the development of new antimicrobial strategies.

PMID- 22860902
TI  - The impact of genomics on research in diversity and evolution of archaea.
AB  - Since the definition of archaea as a separate domain of life along with bacteria
      and eukaryotes, they have become one of the most interesting objects of modern
      microbiology, molecular biology, and biochemistry. Sequencing and analysis of
      archaeal genomes were especially important for studies on archaea because of a
      limited availability of genetic tools for the majority of these microorganisms
      and problems associated with their cultivation. Fifteen years since the
      publication of the first genome of an archaeon, more than one hundred complete
      genome sequences of representatives of different phylogenetic groups have been
      determined. Analysis of these genomes has expanded our knowledge of biology of
      archaea, their diversity and evolution, and allowed identification and
      characterization of new deep phylogenetic lineages of archaea. The development of
      genome technologies has allowed sequencing the genomes of uncultivated archaea
      directly from enrichment cultures, metagenomic samples, and even from single
      cells. Insights have been gained into the evolution of key biochemical processes
      in archaea, such as cell division and DNA replication, the role of horizontal
      gene transfer in the evolution of archaea, and new relationships between archaea
      and eukaryotes have been revealed.

PMID- 22860900
TI  - Impact of HIV-specialized pharmacies on adherence and persistence with
      antiretroviral therapy.
AB  - Patient adherence (the degree to which patients follow their therapeutic regimen
      as prescribed within a set period of time) and persistence (the time to treatment
      discontinuation, with a permissible gap) with drug therapy are essential
      components of HIV/AIDS treatment. Select community pharmacies offer specialized
      services for HIV/AIDS patients to help combat some of the barriers to adherence
      and persistence. We assessed adherence and persistence with antiretroviral
      therapy (ART) for patients using HIV-specialized pharmacies in nine cities from
      seven states compared to traditional community pharmacy users over a 1-year
      period. Data were limited to one pharmacy chain. Propensity scoring was used to
      obtain 1:1 matches for "Specialized" and "Traditional" pharmacy users based on
      age, gender, number of prescription-inferred chronic conditions (obtained by
      mapping a patient's prescriptions to the Medi-Span Drug Indications Database),
      and presence of prescription anxiety and/or depression medication, resulting in
      7064 patients in each group. Proportion of days covered (PDC) was used to measure
      adherence. Specialized pharmacy users had a significantly greater mean (74.1%
      versus 69.2%, p<0.0001) and median (90.3% versus 86.3%, p<0.0001) PDC. A greater
      percentage of patients in the Specialized group were able to obtain a PDC of 95%
      or better (39.3% versus 35.5%). Patients in the Specialized group were
      significantly more persistent (p=0.0117). Community pharmacies specialized in HIV
      services may be effective avenues for helping patients achieve greater adherence
      and persistence with ART. Given the value of specialized community pharmacies,
      payers should consider implementing policies to encourage the use of such
      pharmacies for filling ART.

PMID- 22860903
TI  - MicroRNAs: possible role in pathogenesis of Parkinson's disease.
AB  - Parkinson's disease is one of the most common human neurodegenerative disorders
      caused by the loss of dopaminergic neurons from the substantia nigra pars
      compacta of human brain. However, causes and mechanisms of the progression of the
      disease are not yet fully clarified. To date, investigation of the role of miRNAs
      in norm and pathology is one of the most intriguing and actively developing areas
      in molecular biology. MiRNAs regulate expression of a variety of genes and can be
      implicated in pathogenesis of various diseases. Possible role of miRNAs in
      pathogenesis of Parkinson's disease is discussed in this review.

PMID- 22860904
TI  - Serine proteases of small intestine mucosa--localization, functional properties,
      and physiological role.
AB  - In this review we present data about small intestine serine proteases, which are
      a considerable part of the proteolytic apparatus in this major part of the
      gastrointestinal tract. Serine proteases of intestinal epitheliocytes, their
      structural-functional features, cellular localization, physiological substrates,
      and mechanisms of activity regulation are examined. Information about biochemical
      and functional properties of serine proteases is presented in a common context
      with morphological and physiological data, this being the basis for understanding
      the functional processes taking place in upper part of the intestine. Serine
      proteases play a key role in the physiology of the small intestine and provide
      the normal functioning of this organ as part of the digestive system in which
      hydrolysis and suction of food substances occur. They participate in renewal and
      remodeling of tissues, retractive activity of smooth musculature, hormonal
      regulation, and defense mechanisms of the intestine.

PMID- 22860905
TI  - Mass spectrometric approaches to study enveloped viruses: new possibilities for
      structural biology and prophylactic medicine.
AB  - This review considers principles of the use of mass spectrometry for the study of
      biological macromolecules. Some examples of protein identification, virion
      proteomics, testing vaccine preparations, and strain surveillance are
      represented. Possibilities of structural characterization of viral proteins and
      their posttranslational modifications are shown. The authors' studies by MALDI-MS
      on S-acylation of glycoproteins from various families of enveloped viruses and on
      oligomerization of the influenza virus hemagglutinin transmembrane domains are
      summarized.

PMID- 22860906
TI  - Quinone-dependent alcohol dehydrogenases and FAD-dependent alcohol oxidases.
AB  - This review considers quinone-dependent alcohol dehydrogenases and FAD-dependent
      alcohol oxidases, enzymes that are present in numerous methylotrophic eu- and
      prokaryotes and significantly differ in their primary and quaternary structure.
      The cofactors of the enzymes are bound to the protein polypeptide chain through
      ionic and hydrophobic interactions. Microorganisms containing these enzymes are
      described. Methods for purification of the enzymes, their physicochemical
      properties, and spatial structures are considered. The supposed mechanism of
      action and practical application of these enzymes as well as their producers are
      discussed.

PMID- 22860907
TI  - Role of EctR as transcriptional regulator of ectoine biosynthesis genes in
      Methylophaga thalassica.
AB  - In the halophilic aerobic methylotrophic bacterium Methylophaga thalassica, the
      genes encoding the enzymes for biosynthesis of the osmoprotectant ectoine were
      shown to be located in operon ectABC-ask. Transcription of the ect-operon was
      started from the two promoters homologous to the sigma(70)-dependent promoter of
      Escherichia coli and regulated by protein EctR, whose encoding gene, ectR, is
      transcribed from three promoters. Genes homologous to ectR of methylotrophs were
      found in clusters of ectoine biosynthesis genes in some non-methylotrophic
      halophilic bacteria. EctR proteins of methylotrophic and heterotrophic halophiles
      belong to the MarR-family of transcriptional regulators but form a separate
      branch on the phylogenetic tree of the MarR proteins.

PMID- 22860908
TI  - Identification of intracellular Spiroplasma melliferum metabolites by the HPLC-MS
      method.
AB  - In contrast to the abundance of systems-oriented approaches describing changes on
      the transcriptome or proteome level, relatively few studies have employed the
      metabolome. The goal of the presented research was to identify as many
      intracellular metabolites as possible in a Spiroplasma melliferum extract by flow
      injection time-of-flight mass spectrometry. The Mollicutes class bacterium S.
      melliferum is a member of a unique category of bacteria that have in common the
      absence of a cell wall, a reduced genome, and simplified metabolic pathways.
      Metabolite identification was confirmed by fragmentation of previously detected
      ions by target mass spectrometry. The selected liquid chromatography approach,
      hydrophilic interaction chromatography with amino and silica columns, effectively
      separates highly polar cellular metabolites prior to their detection on a high
      accuracy mass spectrometer in positive and negative acquisition mode for each
      column. Here we present reliable measurement of 76 metabolites, including
      components of sugar, amino acid, and nucleotide metabolism. We have identified
      about a third of the possible intracellular S. melliferum metabolites predicted
      by genome annotation.

PMID- 22860909
TI  - Catalytic properties and amino acid sequence of endo-1->3-beta-D-glucanase from
      the marine mollusk Tapes literata.
AB  - A specific 1->3-beta-D-glucanase with molecular mass 37 kDa was isolated in
      homogeneous state from crystalline style of the commercial marine mollusk Tapes
      literata. It exhibits maximal activity within the pH range from 4.5 to 7.5 at 45
      degrees C. The 1->3-beta-D-glucanase catalyzes hydrolysis of beta-1->3 bonds in
      glucans as an endoenzyme with retention of bond configuration, and it has
      transglycosylating activity. The K(m) for hydrolysis of laminaran is 0.25 mg/ml.
      The enzyme is classified as a glucan endo-(1->3)-beta-D-glucosidase (EC
      3.2.1.39). The cDNA encoding this 1->3-beta-D-glucanase from T. literata was
      sequenced, and the amino acid sequence of the enzyme was determined. The endo-1
      >3-beta-D-glucanase from T. literata was assigned to the 16th structural family
      (GHF 16) of O-glycoside hydrolases.

PMID- 22860910
TI  - 40-kDa actin-binding protein of thin filaments of the mussel Crenomytilus
      grayanus inhibits the strong bond formation between actin and myosin head during
      the ATPase cycle.
AB  - Mobility and spatial orientation of a novel 40-kDa actin-binding protein from the
      smooth muscle of the mussel Crenomytilus grayanus was studied by polarized
      fluorometry. The influence of this protein on orientation and mobility of the
      myosin heads was investigated during modeling the different stages of the ATPase
      cycle. The 40-kDa actin-binding protein affected the strong actin-myosin binding.
      We suggest that the 40-kDa actin-binding protein is involved in regulation of the
      actin-myosin interaction in the smooth muscle of the mussel.

PMID- 22860911
TI  - Domain motions of class I release factor induced by binding with class II release
      factor from Euplotes octocarinatus.
AB  - The binding of both factors (eRF1 and eRF3) is essential for fast kinetics of the
      termination of protein translation. The C-terminal domain of eRF1 is known to
      interact with the C domain of eRF3. Eo-eRF1b contains two highly conserved
      tryptophan residues (W-11 and W-373), W-11 located in the Eo-eRF1b N domain and W
      373 located in the Eo-eRF1b C domain. Fluorimetry was used to study the
      interactions of the proteins. When binding with Eo-eRF3Cm6, the emission peak of
      Eo-eRF1b is blue shifted, while the emission peak of Eo-eRF1bC has no notable
      change. Our results suggest that the eRF1-eRF3 interaction induces the N and C
      domain of eRF1b to become closer to each other.

PMID- 22860912
TI  - Effect of calcium ions on electron transfer between hemes a and a(3) in
      cytochrome c oxidase.
AB  - Kinetics of the reduction of the hemes in cytochrome c oxidase in the presence of
      high concentration of ruthenium(III)hexaammine chloride was examined using a
      stopped-flow spectrophotometer. Upon mixing of the oxidized enzyme with
      dithionite and Ru(NH(3))(6)(3+), three well-resolved phases were observed: heme a
      reduction reaching completion within a few milliseconds is followed by two slow
      phases of heme a(3) reduction. The difference spectrum of heme a(3) reduction in
      the visible region is characterized by a maximum at ~612 nm, rather than at 603
      nm as was believed earlier. It is shown that in the case of bovine heart
      cytochrome c oxidase containing a special cation-binding site in which reversible
      binding of calcium ion occurs, heme a(3) reduction is slowed down by low
      concentrations of Ca(2+). The effect is absent in the case of the bacterial
      cytochrome oxidase in which the cation-binding site contains a tightly bound
      Ca(2+) ion. The data corroborate the inhibition of the cytochrome oxidase
      enzymatic activity by Ca(2+) ions discovered earlier and indicate that the cation
      affects intramolecular electron transfer.

PMID- 22860913
TI  - Role of prodigiosin and chitinases in antagonistic activity of the bacterium
      Serratia marcescens against the fungus Didymella applanata.
AB  - The molecular features of antagonism of the bacterium Serratia marcescens against
      the plant pathogenic fungus Didymella applanata have been studied. The chitinases
      and the red pigment prodigiosin (PG) of S. marcescens were isolated and
      characterized. Specific antifungal activity of the purified PG and chitinases
      against D. applanata was tested in vitro. The antagonistic properties of several
      S. marcescens strains exhibiting different levels of PG and chitinase production
      were analyzed in vitro with regard to D. applanata. It was found that the ability
      of S. marcescens to suppress the vital functions of D. applanata depends mainly
      on the level of PG production, whereas chitinase production does not provide the
      bacterium with any competitive advantage over the fungus.

PMID- 22860914
TI  - Evaluation of the electrical potential on the membrane of the extremely
      alkaliphilic bacterium Thioalkalivibrio.
AB  - The electrical potential on the membrane was measured in cells of strains AL2 and
      ALJ15 of the extremely alkaliphilic bacterium Thioalkalivibrio versutus using the
      penetrating cation tetraphenylphosphonium (TPP(+)) and a TPP(+)-selective
      electrode. The potentials were -228 +/- 5 and -224 +/- 5 mV, respectively, i.e.
      higher than in most alkaliphilic bacteria. Membrane potential in the cells was
      estimated by measuring the inner cell volume by two independent methods: (1)
      estimation of total cell volume by light microscopy and (2) estimation of the
      inner aqueous volume of the cells with allowance for the distribution difference
      of tritium labeled water penetrating through the membranes and a nonpenetrating
      colored protein. The inner cell volume was 2.4 +/- 0.2 and 2.2 +/- 0.1 ul/mg of
      cell protein by the two methods, respectively. Computer computation was used as
      an alternative to manual calculation to count the number of cells for estimation
      of total cell volume.

PMID- 22860915
TI  - Impact on N-glycosylation profile of monoclonal anti-D antibodies as a way to
      control their immunoregulatory and cytotoxic properties.
AB  - Prophylaxis of hemolytic disease of newborns is based on the ability of
      polyclonal anti-D antibodies for suppressing maternal immune response against D
      positive fetal red blood cells. The immunosuppressive effect of anti-D antibody
      is mediated by interaction between its Fc-fragment and low-affinity IgG Fc
      receptor (FcgammaR) on the immune cell. No clinically effective monoclonal anti-D
      antibody (mAb) that can replace polyclonal anti-D immunoglobulin has been
      developed yet. The goals of this study were comparison of structural and
      functional properties of human anti-D polyclonal and monoclonal Abs and
      assessment of the possibility to manipulate the effector properties of the mAb. N
      Glycosylation and particularly the content of nonfucosylated glycans are crucial
      for affinity of mAb to FcgammaRIIIA, which plays the key role in the clearance of
      sensitized cells. We studied and compared glycoprofiles and FcgammaRIIIA-mediated
      hemolytic ability of human polyclonal antibodies and anti-D mAbs produced by
      human B-cell lines, human-rodent heterohybridomas, and a human non-lymphoid cell
      line PER.C6. Replacement of producing cell line and use of glycosylation
      modulators can convert an inert mAb into an active one. Nevertheless, rodent cell
      lines, as well as human non-lymphoid cells, distort natural glycosylation of
      human IgG and could lead to the loss of immunosuppressive properties. All of the
      anti-D mAbs secreted by human B-cell lines have a glycoprofile close to human
      serum IgG. Hence, the constant ratio of IgG glycoforms in human serum is
      predetermined by glycosylation at the level of the individual antibody-producing
      cell. The anti-D fraction of polyclonal anti-D immunoglobulin compared to the
      total human IgG contains more nonfucosylated glycans. Thus, only human
      transformed B-cells are an appropriate source for efficient anti-D mAbs that can
      imitate the action of polyclonal anti-D IgG.

PMID- 22860916
TI  - HDAC1/DNMT3A-containing complex is associated with suppression of Oct4 in
      cervical cancer cells.
AB  - Octamer-binding transcription factor 4 (Oct4), an important embryonic
      transcriptional factor, is highly expressed in several tumors and is considered
      as a hallmark of cancer stem cells. Knowledge about the expression and regulatory
      mechanisms of Oct4 can contribute to the treatment of cancers. As for cervical
      cancer, however, details remain obscure about Oct4 expression and its regulatory
      mechanism. In this study, we found that the level of Oct4 in human papillomavirus
      16 (HPV16)- positive cervical cancer cells (CaSki cells) was higher than that in
      HPV-negative cervical cancer cells (C-33A cells), whereas both the level of
      histone deacetylase 1 (HDAC1) and DNA methyltransferase 3A (DNMT3A) were lower in
      CaSki cells than those in C-33A cells. Treatment with valproic acid, an HDAC
      inhibitor, could significantly increase the expression of Oct4 in C-33A cells,
      but only slightly increased Oct4 in CaSki cells. Co-immunoprecipitation assays
      showed that HDAC1 and DNMT3A existed in a common complex. The co
      immunoprecipitated DNMT3A or HDAC1 was dose-dependently decreased with valproic
      acid treatment. These results indicated that HDAC1/DNMT3A-containing complex is
      associated with the suppression of Oct4 in cervical cancer cells, and the
      activity of HDAC1 is required in the repression of Oct4.

PMID- 22860917
TI  - Expression, purification, and secondary structure characterization of recombinant
      KCTD1.
AB  - Potassium channel tetramerization domain containing 1 (KCTD1) contains a BTB
      domain, which can facilitate protein-protein interactions that may be involved in
      the regulation of signaling pathways. Here we describe an expression and
      purification system that can provide a significant amount of recombinant KCTD1
      from Escherichia coli. The cDNA encoding human KCTD1 was amplified and cloned
      into the expression vector pET-30a(+). The recombinant protein was expressed in
      E. coli BL21(DE3) cells and subsequently purified using affinity chromatography.
      To confirm that KCTD1 was correctly expressed and folded, the molecular weight
      and conformation were analyzed using mass spectroscopy, Western blot, and
      circular dichroism. Optimizing KCTD1 expression and investigating its secondary
      structure will provide valuable information for future structural and functional
      studies of KCTD1 and KCTD family proteins.

PMID- 22860918
TI  - Screening of ragdoll cats for kidney disease: a retrospective evaluation.
AB  - OBJECTIVES: To assess the prevalence of renal abnormalities in ragdoll cats.
      Ragdoll breeders often warn clients to watch for future renal problems, mainly
      due to chronic interstitial nephritis and polycystic kidney disease. Therefore,
      ragdoll screening by abdominal ultrasonography, measurement of serum creatinine
      and urea concentrations and genetic testing is often performed without documented
      scientific evidence of increased risk of renal disease. METHODS: Retrospective
      evaluation of ragdoll screening for renal disease at one institution over an
      eight-year period. RESULTS: Renal ultrasonography was performed in 244 healthy
      ragdoll cats. Seven cats were positive for polycystic kidney disease, 21 were
      suspected to have chronic kidney disease, 8 had abnormalities of unknown
      significance and 2 cats had only one visible kidney. Cats suspected to have
      chronic kidney disease were significantly older and had significantly higher
      serum urea and creatinine concentrations than cats with normal renal
      ultrasonography. All 125 genetically tested cats were negative for polycystic
      kidney disease. However, only one of the seven ultrasonographically positive cats
      underwent genetic testing for polycystic kidney disease. CLINICAL SIGNIFICANCE:
      Ultrasonographic findings compatible with chronic kidney disease were observed in
      almost 10% of cats, and polycystic kidney disease occurred at a low prevalence
      (<3%) in this ragdoll population. Further studies are required to elucidate if
      ragdoll cats are predisposed to chronic kidney disease.

PMID- 22860919
TI  - Identifying the core competencies of mental health telephone triage.
AB  - AIMS AND OBJECTIVES: The primary aim of this study was to identify the core
      competencies of mental health telephone triage, including key role tasks, skills,
      knowledge and responsibilities, in which clinicians are required to be competent
      to perform safe and effective triage. BACKGROUND: Recent global trends indicate
      an increased reliance on telephone-based health services to facilitate access to
      health care across large populations. The trend towards telephone-based health
      services has also extended to mental health settings, evidenced by the growing
      number of mental health telephone triage services providing 24-hour access to
      specialist mental health assessment and treatment. Mental health telephone triage
      services are critical to the early identification of mental health problems and
      the provision of timely, appropriate interventions. In spite of the rapid growth
      in mental health telephone triage and the important role these services play in
      the assessment and management of mental illness and related risks, there has been
      very little research investigating this area of practice. DESIGN: An
      observational design was employed to address the research aims. METHODS:
      Structured observations (using dual wireless headphones) were undertaken on 197
      occasions of mental health telephone triage over a three-month period from
      January to March 2011. RESULTS: The research identified seven core areas of
      mental health telephone triage practice in which clinicians are required to be
      competent in to perform effective mental health telephone triage, including
      opening the call; performing mental status examination; risk assessment; planning
      and action; termination of call; referral and reporting; and documentation.
      CONCLUSIONS: The findings of this research contribute to the evidence base for
      mental health telephone triage by articulating the core competencies for
      practice. RELEVANCE TO CLINICAL PRACTICE: The mental health telephone triage
      competencies identified in this research may be used to define an evidence-based
      framework for mental health telephone triage practice that aims to improve the
      quality, consistency and accuracy of telephone-based mental health triage
      assessment.

PMID- 22860920
TI  - Making do with what we have: use your bootstraps.

PMID- 22860921
TI  - Waldenstrom macroglobulinemia: my way.
AB  - Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma. A serum monoclonal
      IgM protein is required to establish this diagnosis. The clinical features
      patients develop include normochromic normocytic anemia, thrombocytopenia,
      hepatosplenomegaly, lymphadenopathy and signs of hyperviscosity. The
      International Staging System for Waldenstrom macroglobulinemia divides patients
      prognostically based on age, hemoglobin, platelet count, IgM level, and beta(2)
      microglobulin. Some patients with Waldenstrom macroglobulinemia have a smoldering
      form and can be observed without intervention. Active agents in the treatment of
      Waldenstrom macroglobulinemia include rituximab, chlorambucil, cyclophosphamide,
      fludarabine, bortezomib, lenalidomide, bendamustine, everolimus, and alemtuzumab.
      The current preferred Mayo Clinic non-study treatment is rituximab,
      cyclophosphamide, and dexamethasone. The median survival associated with this
      disease is now over 10 years.

PMID- 22860922
TI  - Pyrazine derivatives: a patent review (2008 - present).
AB  - INTRODUCTION: Pyrazines derivatives are well-known and important two-nitrogen
      containing six-membered ring aromatic heterocyclic compounds and can carry
      substituents at one or more of the four ring carbon atoms. Pyrazines are a class
      of compounds that occur in nature and various methods have been worked out for
      their synthesis. A large number of pyrazine derivatives have been found to
      possess diverse pharmacological properties, which has caused an increasing
      interest by researchers in this core. AREA COVERED: This review provides a
      comprehensive review of the pyrazines derivatives patented between the years 2008
      to 2012 as potential active compounds. The patent databases SciFinder and
      esp@cenet were used to locate patent applications that were published between
      2008 to present. Information from articles published was also included. EXPERT
      OPINION: The diversity of pyrazines derivatives found in organisms in nature with
      different applications began to arouse the interest of research in this nucleus.
      The pyrazines derivatives have numerous prominent pharmacological effects, such
      as antibacterial, antifungal, antimycobacterial, anti-inflammatory, analgesic,
      anticancer for different types, antidiabetic, treatment for arteriosclerosis,
      antiviral. It's the time to conduct further studies aimed at rationalizing the
      biological activities found in order to develop more effective and clinically
      interesting compounds.

PMID- 22860923
TI  - Tissue-specific and developmental modifications of grape cell walls influence the
      adsorption of proanthocyanidins.
AB  - Cell wall material from  Vitis vinifera  L. cv. Cabernet Sauvignon grape skin and
      flesh was isolated at different stages of grape maturity to determine whether
      developmental changes in cell wall composition in different tissue types
      influence the binding of proanthocyanidins (PAs). Trends in cell wall adsorption
      of, and selectivity for, PAs were determined using two skin PAs that differed in
      their average molecular masses. Flesh cell walls consistently bound a higher
      amount of PA than those from skin. Key structural differences that reduced PA
      adsorption in skin cell walls by comparison with flesh cell walls were
      endogenously higher concentrations of insoluble PA, Klason lignin, and lower cell
      wall-bound protein. These differences may confer reduced flexibility and porosity
      of skin cell walls relative to flesh cell walls. Analysis of skin and flesh cell
      wall properties revealed that the onset of ripening was associated with a loss of
      type I arabinogalactan and galacturonic acid, which indicated a degradation of
      pectin within the cell wall. Flesh cell walls consistently bound PAs of larger
      molecular mass, and changes in PA adsorption properties after the onset of
      ripening were minor. For skin cell walls, adsorption of PA was lowest immediately
      following solubilization of galacturonic acid, and high molecular mass PAs were
      poorly bound. As ripening progressed, PAs of higher molecular mass were
      selectively adsorbed by skin cell walls, which indicates that ongoing cell wall
      remodeling during ripening may confer an increased porosity within the skin cell
      wall matrix, resulting in a greater adsorption of PA within a permeable
      structure.

PMID- 22860924
TI  - Mulberry leaf extract inhibits cancer cell stemness in neuroblastoma.
AB  - Emerging evidence proposes that most cancers originate from a rare subpopulation
      of cells, called cancer stem cells (CSCs), which possess characteristics
      including differentiation, self-renewal, and tumorigenicity. Currently, available
      therapeutic agents cannot effectively eliminate CSCs. Therefore, the development
      of a nontoxic, natural treatment that can either overcome chemoresistance or
      promote the elimination of CSCs is highly desirable. The current study examined
      whether mulberry leaf (ML) ethanolic extract can effectively eliminate
      neuroblastoma stem cell-like population. Our data demonstrated that 10-40 MUg/ml
      of ML extract significantly enhanced differentiation by elongating neurites and
      reducing clonogenicity and sphere formation as shown by the decreased expression
      of stem cell markers and increased expression of differentiation markers. The
      knock-down of delta-like 1 homologue by siRNA enhanced the significant inhibitory
      effects of 40 MUg/ml of ML extract on colony formation. Furthermore,
      phosphorylation of the extracellular signal-regulated kinase (ERK) was increased
      by 20 or 40 MUg/ml of ML extract and the MEK/ERK inhibitors completely blocked
      differentiation induced by the extract. Taken together, these findings provide
      experimental evidence that ML may have chemopreventive effects on neuroblastoma
      cells by inhibiting CSCs characteristics as well as regulating CSCs pathways,
      which may provide a therapeutic option for controlling the growth of
      neuroblastoma cells.

PMID- 22860980
TI  - Definitive radical external beam radiotherapy for rectal cancer: evaluation of
      local effectiveness and risk of late small bowel damage.
AB  - AIM: To present a retrospective analysis of results of definitive radiotherapy
      for rectal cancer. MATERIAL AND METHODS: Forty-one consecutive patients with
      rectal cancer (32% primary, 61% pelvic recurrence and 7% after R2 resection) who
      could not be treated with surgery underwent external beam radiotherapy. A median
      tumour dose of 64 Gy was given with 1.8-2.5 Gy per fraction using 2D or 3D
      technique. In 46% of patients, concurrent 5-Fu-based chemotherapy was given. The
      median follow-up was 54 months. RESULTS: Clinical complete response was achieved
      in 39% of patients. Five-year cumulative incidence of local failure, overall
      survival and cancer specific survival were 76%, 26% and 30%, respectively. Of 11
      patients with local control, in five cases the tumour was larger than 5 cm and in
      the other five the tumour was fixed. Two patients, regarded as locally controlled
      had non-progressive tumour without local symptoms at the last follow-up of 54 and
      118 months post-radiotherapy. Late toxicity occurred in 22% of patients, all with
      acceptable severity. There was no bowel obstruction requiring surgery despite
      that in 18 patients the small bowel dose was >60 Gy to a mean volume of 51 cm(3).
      CONCLUSION: Definitive radio(chemo)therapy provides a chance for local control
      even in patients with large fixed or recurrent rectal cancer.

PMID- 22860981
TI  - Homocysteine, folate, vitamin B12 and B6 in mothers of children with neural tube
      defects in Xinjiang, China.
AB  - AIM: To investigate the maternal homocysteine (Hcy), folate, vitamin B(12) and
      B(6) , and their relations to neural tube defects (NTDs). METHODS: Thirty mothers
      of NTDs offspring and another 60 mothers of normal children were enrolled as the
      patient and control groups from Xinjiang, China, from January 2008 to May 2011.
      The plasma levels of Hcy, folate, vitamin B(12) and B(6) were measured and
      compared between the two groups. RESULTS: The morbidity of NTDs was 2.44% in
      Xinjiang. The Hcy was significantly higher in patient group than in control group
      (15.1 +/- 7.8 vs. 8.5 +/- 4.0 MUmol/L, p < 0.001). The folate in patient group
      (9.7 +/- 8.1 MUg/L) was lower than in control group (15.0 +/- 8.1 MUg/L, p <
      0.001). The vitamin B(12) was 181.3 +/- 107.7 and 394.3 +/- 386.3 ng/L in patient
      and control groups, respectively, with a significant difference (p < 0.001). The
      abnormal frequency of Hcy and vitamin B(12) was statistically different in two
      groups. The difference of vitamin B(6) between the patients and controls was
      marginal (48.7 +/- 16.5 vs. 42.0 +/- 10.5 mg/L, p = 0.051). Moreover, folate and
      vitamin B(12) levels were negatively correlated with Hcy while vitamin B(6) was
      positively correlated with Hcy. Positive correlation was observed between folate
      and vitamin B(12) levels. CONCLUSION: Our data confirm that higher Hcy, lower
      folate and vitamin B(12) are risk factors for NTDs. Besides folate, vitamin B(12)
      should be supplied to decrease NTDs occurrence. Further study is required to
      investigate the levels and accurate role of vitamin B(6).

PMID- 22860982
TI  - Achieving yield gains in wheat.
AB  - Wheat provides 20% of calories and protein consumed by humans. Recent genetic
      gains are <1% per annum (p.a.), insufficient to meet future demand. The Wheat
      Yield Consortium brings expertise in photosynthesis, crop adaptation and genetics
      to a common breeding platform. Theory suggest radiation use efficiency (RUE) of
      wheat could be increased ~50%; strategies include modifying specificity,
      catalytic rate and regulation of Rubisco, up-regulating Calvin cycle enzymes,
      introducing chloroplast CO(2) concentrating mechanisms, optimizing light and N
      distribution of canopies while minimizing photoinhibition, and increasing spike
      photosynthesis. Maximum yield expression will also require dynamic optimization
      of source: sink so that dry matter partitioning to reproductive structures is not
      at the cost of the roots, stems and leaves needed to maintain physiological and
      structural integrity. Crop development should favour spike fertility to maximize
      harvest index so phenology must be tailored to different photoperiods, and
      sensitivity to unpredictable weather must be modulated to reduce conservative
      responses that reduce harvest index. Strategic crossing of complementary
      physiological traits will be augmented with wide crossing, while genome-wide
      selection and high throughput phenotyping and genotyping will increase efficiency
      of progeny screening. To ensure investment in breeding achieves agronomic impact,
      sustainable crop management must also be promoted through crop improvement
      networks.

PMID- 22860983
TI  - Lewis acid-triggered selective zincation of chromones, quinolones, and
      thiochromones: application to the preparation of natural flavones and
      isoflavones.
AB  - A Lewis acid-triggered zincation allows the regioselective metalation of various
      chromones and quinolones. In the absence of MgCl(2), a C(3) zincation is
      observed, whereas in the presence of MgCl(2) or a related Lewis acid, C(2)
      zincation occurs. Applications to a natural flavone, isoflavone, and quinolone
      are shown.

PMID- 22860984
TI  - Imparting chemical stability in nanoparticulate silver via a conjugated polymer
      casing approach.
AB  - Only limited information is available on the design and synthesis of functional
      materials for preventing corrosion of metal nanostructures. In the nanometer
      regime, even noble metals are subject to chemical attack. Here, the corrosion
      behavior of noble metal nanoparticles coated with a conjugated polymer nanolayer
      was explored for the first time. Specifically, electrochemical corrosion and
      sulfur tarnishing behaviors were examined for Ag-polypyrrole (PPy) core-shell
      nanoparticles using potentiodynamic polarization and spectrophotometric analysis,
      respectively. First, the Ag-PPy nanoparticles exhibited enhanced resistance to
      electrochemically induced corrosion compared to their exposed silver
      counterparts. Briefly, a neutral PPy shell provided the highest protection
      efficiency (75.5%), followed by sulfate ion- (61.3%) and dodecylbenzenesulfonate
      ion- (53.6%) doped PPy shells. However, the doping of the PPy shell with chloride
      ion induced an adverse effect (protection efficiency, -120%). Second, upon
      exposure to sulfide ions, the Ag-PPy nanoparticles preserved their morphology and
      colloidal stability while the bare silver analog underwent significant structural
      deformation. To further understand the function of the PPy shell as a protection
      layer for the silver core, the catalytic activity of the nanostructures was also
      evaluated. Using the reduction of 4-nitrophenol as a representative example of a
      catalytic reaction, the rate constant for that reduction using the PPy encased Ag
      nanoparticles was found to be 1.1 * 10(-3) s(-1), which is approximately 33% less
      than that determined for the parent silver. These results demonstrate that PPy
      can serve as both an electrical and chemical barrier for mitigating undesirable
      chemical degradation in corrosive environments, as well as provide a simple
      physical barrier to corrosive substances under appropriate conditions.

PMID- 22860985
TI  - Chinese mothers and adolescents' views of authority and autonomy: a study of
      parent-adolescent conflict in urban and rural China.
AB  - Eighty-five dyads of eighth-grade adolescents (mean age=14.15 years, SD=0.39) and
      their mothers in China (30 dyads from urban one-child families, 27 from urban
      multiple-children families, and 28 from rural multiple-children families) were
      interviewed individually. They described daily parent-adolescent conflicts,
      justified their perspectives on disputes, and evaluated conflict resolutions. The
      results indicated that across urban and rural areas, for both one-child and
      multiple-children families, adolescents differed significantly from their mothers
      in their views of parental authority and individual autonomy. The results also
      showed several regional differences, pointing to the importance of considering
      the specific context in which conflicts occur.

PMID- 22860986
TI  - Measurement of prothrombin time and activated partial thromboplastin time in
      citrated whole blood samples from clinically ill dogs following storage.
AB  - OBJECTIVES: To assess the reliability of prothrombin time and activated partial
      thromboplastin time results generated from citrated whole blood samples following
      short-term storage at room temperature. METHODS: Clotting times were measured in
      blood samples from 40 dogs that showed a variety of clinical signs. Before
      measurement of prothrombin time and activated partial thromboplastin time in
      citrated plasma, whole blood samples were split in three aliquots; one was
      processed within 30 minutes of collection (fresh) while the remaining two were
      stored unseparated at room temperature for 24 (24RT) or 48 (48RT) hours. RESULTS:
      The median prothrombin time for the 24RT (7 seconds) and 48RT (7.2 seconds)
      samples were not significantly different to those obtained from the fresh (7.1
      seconds) samples but the median activated partial thromboplastin time for the
      24RT (12.6 seconds) and 48RT (12 seconds) samples were significantly shorter than
      those obtained from the fresh samples (14.2 seconds). CLINICAL SIGNIFICANCE:
      Storage of citrated whole blood at room temperature for 24 or 48 hours did not
      significantly alter the measurement of prothrombin time but resulted in
      significantly shorter activated partial thromboplastin time results.
      Extrapolating from these findings, it is proposed that unseparated clinical
      samples that are submitted to an external diagnostic laboratory for the
      performance of clotting times, may generate reliable prothrombin time but
      unreliable activated partial thromboplastin time results.

PMID- 22860987
TI  - FeCl3-catalyzed stereoselective construction of spirooxindole
      tetrahydroquinolines via tandem 1,5-hydride transfer/ring closure.
AB  - An efficient FeCl(3)-catalyzed stereoselective intramolecular tandem 1,5-hydride
      transfer/ring closure reaction was developed. The method allows for the formation
      of structurally diverse spirooxindole tetrahydroquinolines in high yields (up to
      98%) with good to excellent levels of diastereoselectivity (up to 99:1 dr). The
      catalytic enantioselective variant of this process was also investigated
      preliminarily with a chiral BINOL-derived phosphoric acid.

PMID- 22860988
TI  - Dentition, dental health habits, and dementia: the Leisure World Cohort Study.
AB  - OBJECTIVES: To explore the association between dentition and dental health
      behaviors and incident dementia. DESIGN: Longitudinal cohort. SETTING: Leisure
      World, Laguna Hills, CA; a retirement community. PARTICIPANTS: Five thousand four
      hundred sixty-eight older (median age 81) adults followed from 1992 to 2010.
      MEASUREMENTS: Questions regarding dental health focused on number of natural
      teeth, dentures worn, number of visits to a dentist, and oral health habits.
      Dementia status was determined from in-person evaluations, follow-up
      questionnaires, hospital data, and death certificates. Estimates of dementia risk
      were calculated using Cox regression analysis in men and women separately.
      RESULTS: Men with inadequate natural masticatory function who did not wear
      dentures had a 91% greater risk of dementia than those with adequate natural
      masticatory function (>= 10 upper teeth and >= 6 lower teeth). This risk was also
      greater in women but not significantly so. Dentate individuals who reported not
      brushing their teeth daily had a 22% to 65% greater risk of dementia than those
      who brushed three times daily. CONCLUSION: In addition to helping maintain
      natural, healthy, functional teeth, oral health behaviors are associated with
      lower risk of dementia in older adults.

PMID- 22860989
TI  - Lichen sclerosus and atopy in boys: coincidence or correlation?
AB  - BACKGROUND: Lichen sclerosus (LS) is a sclerosing skin disease of presumably
      autoimmune origin affecting mainly the anogenital area. The aetiology is not
      completely understood. Comorbidity between genital LS and atopy in girls has been
      described but so far no controlled study has been performed. OBJECTIVES: A
      prospective epidemiological case-control study was designed to clarify if there
      is comorbidity between genital LS and atopic skin diathesis (AD) in boys.
      METHODS: The study included a total of 92 boys aged between 1 and 17 years. The
      disease group consisted of 48 boys who underwent surgery for phimosis that was
      histologically confirmed as LS. The control group included 44 boys who were
      circumcised for phimosis for other medical reasons. Both groups were examined and
      the parents were interviewed following the criteria of the validated Diepgen
      atopy score. Patients with a score > 9 were assumed to have AD. RESULTS: Within
      the LS group (median age 8.7 years) 12 boys were diagnosed with AD (25%), while
      there were only three boys with AD (7%) in the control group (median age 5.3
      years). The difference was significant using an age-adjusted logistic regression
      (P < 0.05). Prior to our study nine boys of the LS group (19%) and four boys of
      the control group (9%) had already been diagnosed with AD. CONCLUSIONS: We have
      demonstrated a significant comorbidity between LS and AD in boys. AD seems to be
      a priming precondition for the development of LS in boys.

PMID- 22860990
TI  - Arterial anatomic variations and its influence on transradial coronary procedural
      outcome.
AB  - OBJECTIVES: Our aim was to establish the frequency of arterial anatomic
      variations and its relation to coronary procedural outcome in patients undergoing
      a first transradial coronary procedure. METHODS: This was a single center
      prospective study. A total of 1,446 consecutive patients undergoing their first
      transradial coronary procedure were recruited. Retrograde radial arteriography
      was performed to define radial artery anatomy. If the operator encountered
      serious problems during crossing the subclavian-aortic truncus, retrograde
      subclavian arteriography was also performed. Patient demographics; procedural
      data such as: total procedural duration, the number of catheters and guidewires
      used, the amount of contrast media usage, dose area product (DAP), and
      fluoroscopy time; and vascular complications were recorded. RESULTS: Anatomic
      variations were noted in 270 patients (18.6%), and these patients were
      significantly older (mean age 64.4 +/- 10.4 vs. 59.2 +/- 10.8 years, P < 0.001)
      and more commonly female (46% vs. 33%, P < 0.001) with significantly higher
      procedural failure rates (8.8% vs. 5.6%, P = 0.006). In addition, procedural
      duration (P < 0.001) and fluoroscopy time (P < 0.001) were statistically longer
      in patients with anatomic variations. Anatomic variations also had an adverse
      impact on the amount of contrast agent usage (63.9 +/- 28.3 mL vs. 59.1 +/- 25.3
      mL, P = 0.006) and minor vascular complication rate (P = 0.007). CONCLUSIONS:
      This study indicates that anatomic variation of the arterial path has an adverse
      impact on transradial coronary procedural outcome.

PMID- 22860991
TI  - Ocular disorders and the utility of animal models in the discovery of
      melatoninergic drugs with therapeutic potential.
AB  - INTRODUCTION:   The pineal indole-derived hormone melatonin is a modulator of
      circadian and seasonal rhythms with an important role in ocular health and
      disease. This could be due to specific melatonin receptors that have been
      identified in structures such as cornea, lens, ciliary body, retina, choroid and
      sclera. In addition, a local synthesis of melatonin occurs in several of these
      ocular tissues. AREAS COVERED: The authors review existing literature on the most
      common animal models where ocular melatonin actions have been tested. The
      therapeutic potential of melatonin in diabetic keratopathy and retinopathy,
      keratitis, cataracts, glaucoma, uveitis, age-related macular degeneration and
      retinitis pigmentosa is discussed. Furthermore, the authors comment on the
      usefulness of different animal models for the development of melatoninergic drugs
      with therapeutic potential. EXPERT OPINION: The use of animals for the study of
      ocular diseases and the potentiality of melatonin and its analogs, as future
      therapeutic drugs, should be performed on the basis of a rationale study. It is
      important to note that melatonin receptors seem to be widespread all over the
      eye. This strongly suggests that, in order to modify the physiology and
      biochemistry of malfunctioning ocular tissue, the melatonin receptors which are
      present in that tissue must be first identified. Second there is the need to
      confirm that those receptors targeted perform the desirable responses, and as a
      third measure, to use selective agonists (or antagonists) instead of melatonin.
      However, although some animals mimic ocular pathologies relatively well, and
      these can be used in melatonin studies, there is still a long way to go till some
      of the results obtained in animal models could be used for human therapy.

PMID- 22860992
TI  - Meta-analysis in context.
AB  - AIMS AND OBJECTIVES: To provide a detailed description of the concept, practice
      and relevance of meta-analysis. BACKGROUND: An increasing abundance of research
      contributes to a gap between research and clinical practice. The conduct of meta
      analysis, when carried out appropriately, provides a means by which data may be
      summarised such that it provides important answers for practising clinicians
      pertaining to the strength and direction of the evidence base. DESIGN: A
      discursive design was adopted to encapsulate the current thinking regarding the
      use of meta-analysis. METHODS: A literature review approach was employed to
      provide a narrative summary of the subject of meta-analysis. Meta-analysis is a
      statistical procedure, which involves quantitatively pooling the data from a
      group of independent studies that have looked at the same or similar clinical
      problems, using the same or similar research methods. The data are then
      reanalysed to calculate a pooled estimate of effect and a confidence interval
      around this estimate. RESULTS: The findings from this review indicate that meta
      analysis is a statistical procedure, which involves quantitatively pooling the
      data from a group of independent studies that have looked at the same or similar
      clinical problems, using the same or similar research methods. Correctly
      conducted, meta-analysis provides useful information for practice, identifying
      the strength and direction of the evidence base pertaining to important clinical
      problems. CONCLUSION: Meta-analysis is a useful means by which those in the
      clinical practice setting may clarify the evidence base surrounding a wide
      variety of clinical problems. RELEVANCE TO CLINICAL PRACTICE: The value of meta
      analysis is that this information may be used to guide clinical practice decision
      making and also to direct the development of future research strategies.

PMID- 22860993
TI  - Novel therapeutic targets in chordoma.
AB  - INTRODUCTION: Chordomas are malignant bone tumors arising from notochordal
      remnants. They most commonly occur at the sacrum, skull base, and spine. The gold
      standard treatment for these tumors is a combination of en-bloc resection and
      radiation therapy. AREAS COVERED: Recent genomic studies have identified
      duplication of the gene brachyury as a major susceptibility mutation in familial
      chordomas. Studies on sporadic chordomas have identified several tumor markers,
      using microRNAs and Comparative Genome Hybridization. In this article, we
      highlight current advances in research on the molecular characterization of
      chordomas. EXPERT OPINION: Scientific advances have allowed for the
      identification of numerous tumor markers involved in chordoma pathogenesis. In
      the future, chordoma cell lines will be produced that silence or over-express
      these tumor markers. As we increase our understanding of the mechanism of
      chordoma tumor proliferation, we can expect the development of targeted drug
      therapies.

PMID- 22860994
TI  - Coordination of intercellular Ca(2+) signaling in endothelial cell tubes of mouse
      resistance arteries.
AB  - OBJECTIVE: To test the hypothesis that Ca(2+) responses to GPCR activation are
      coordinated between neighboring ECs of resistance arteries. METHODS: EC tubes
      were freshly isolated from superior epigastric arteries of C57BL/6 mice.
      Intercellular coupling was tested using microinjection of propidium iodide.
      Following loading with fluo-4 dye, intracellular Ca(2+) responses to ACh were
      imaged with confocal microscopy. RESULTS: Cell-to-cell transfer of propidium
      iodide confirmed functional GJCs. A 1 MUm ACh stimulus evoked Ca(2+) responses
      (9.8 +/- 0.8/min, F/F(0) = 3.11 +/- 0.2) which pseudo-line-scan analysis revealed
      as composed of Ca(2+) waves and spatially restricted Ca(2+) release events. A 100
      nm ACh stimulus induced Ca(2+) responses of lower frequency (4.5 +/- 0.7/min) and
      amplitude (F/F(0) = 1.95 +/- 0.11) composed primarily of spatially restricted
      events. The time interval between Ca(2+) waves in adjacent cells (0.79 +/- 0.12
      s) was shorter (p < 0.05) than that between nonadjacent cells (1.56 +/- 0.25 s).
      Spatially restricted Ca(2+) release events had similar frequencies and latencies
      between adjacent and nonadjacent cells. Inhibiting intracellular Ca(2+) release
      with 2-APB, Xestospongin C or thapsigargin eliminated Ca(2+) responses.
      CONCLUSIONS: With moderate GPCR stimulation, localized Ca(2+) release events
      predominate among cells. Greater GPCR stimulation evokes coordinated
      intercellular Ca(2+) waves via the ER. Calcium signaling during GPCR activation
      is complex among cells, varying with stimulus intensity and proximity to actively
      signaling cells.

PMID- 22860995
TI  - The pig as a model for investigating the role of neutrophil serine proteases in
      human inflammatory lung diseases.
AB  - The serine proteases released by activated polymorphonuclear neutrophils [NSPs
      (neutrophil serine proteases)] contribute to a variety of inflammatory lung
      diseases, including CF (cystic fibrosis). They are therefore key targets for the
      development of efficient inhibitors. Although rodent models have contributed to
      our understanding of several diseases, we have previously shown that they are not
      appropriate for testing anti-NSP therapeutic strategies [Kalupov, Brillard
      Bourdet, Dade, Serrano, Wartelle, Guyot, Juliano, Moreau, Belaaouaj and Gauthier
      (2009) J. Biol. Chem. 284, 34084-34091). Thus NSPs must be characterized in an
      animal model that is much more likely to predict how therapies will act in humans
      in order to develop protease inhibitors as drugs. The recently developed CFTR-/-
      (CFTR is CF transmembrane conductance regulator) pig model is a promising
      alternative to the mouse model of CF [Rogers, Stoltz, Meyerholz, Ostedgaard,
      Rokhlina, Taft, Rogan, Pezzulo, Karp, Itani et al. (2008) Science 321, 1837
      1841]. We have isolated blood neutrophils from healthy pigs and determined their
      responses to the bacterial pathogens Pseudomonas aeruginosa and Staphylococcus
      aureus, and the biochemical properties of their NSPs. We used confocal microscopy
      and antibodies directed against their human homologues to show that the three
      NSPs (elastase, protease 3 and cathepsin G) are enzymatically active and present
      on the surface of triggered neutrophils and NETs (neutrophil extracellular
      traps). All of the porcine NSPs are effectively inhibited by human NSP
      inhibitors. We conclude that there is a close functional resemblance between
      porcine and human NSPs. The pig is therefore a suitable animal model for testing
      new NSP inhibitors as anti-inflammatory agents in neutrophil-associated diseases
      such as CF.

PMID- 22860996
TI  - Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells.
AB  - Garlic has been used throughout history for both culinary and medicinal purpose.
      Allicin is a major component of crushed garlic. Although it is sensitive to heat
      and light and easily metabolized into various compounds such as diallyl
      disulfide, diallyl trisulfide, and diallyl sulfide, allicin is still a major
      bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma
      is quite high and ranks among the top 10 cancer-related deaths in Taiwan.
      Although numerous studies have shown the cancer-preventive properties of garlic
      and its components, there is no study on the effect of allicin on the growth of
      human liver cancer cells. In this study, we focused on allicin-induced autophagic
      cell death in human liver cancer Hep G2 cells. Our results indicated that allicin
      induced p53-mediated autophagy and inhibited the viability of human
      hepatocellular carcinoma cell lines. Using Western blotting, we observed that
      allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway,
      and the level of Bcl-2 and increased the expression of AMPK/TSC2 and Beclin-1
      signaling pathways in Hep G2 cells. In addition, the colocalization of LC3-II
      with MitoTracker-Red (labeling mitochondria), resulting in allicin-induced
      degradation of mitochondria, could be observed by confocal laser microscopy. In
      conclusion, allicin of garlic shows great potential as a novel chemopreventive
      agent for the prevention of liver cancer. 

PMID- 22860998
TI  - Detection and distinction of DNT and TNT with a fluorescent conjugated polymer
      using the microwave conductivity technique.
AB  - We report the detection and distinction of dinitrotoluene (DNT) and
      trinitrotoluene (TNT) by the microwave conductivity technique using a
      cyclopentadithiophene-bithiazole-based polymer (CPDT-BT) as sensor. Although the
      conventional fluorescence quenching experiments showed just "turn OFF" of the
      polymer fluorescence for both DNT and TNT, time-resolved microwave conductivity
      (TRMC) revealed that the photoconductivity of the polymer, which is "turned OFF"
      in the pristine state became "ON" in the presence of DNT but remained "OFF" with
      TNT, allowing easy distinction between them. Moreover, the decay rate of the
      transient kinetics was found to be sensitive to the DNT concentration,
      implementing a unique method for the determination of unknown DNT concentration.
      The observations are discussed in viewpoint of charge separation (CS) and
      formation of charge transfer (CT) complex by considering deeper LUMO of TNT than
      DNT calculated from the DFT method. This study brings out a novel technique of
      speedy detection and distinction of environmentally important analytes, an
      alternative to the fluorescence quenching. 

PMID- 22860997
TI  - Health care utilization in HIV-infected patients: assessing the burden of
      hepatitis C virus coinfection.
AB  - Abstract   Health care utilization for HIV-1-infected patients appears to be
      declining in the United States as a result of highly active antiviral therapy
      (HAART); yet the opposite appears true in the HIV/hepatitis C virus (HCV)
      coinfected population. The reasons for this difference are not well understood.
      We examined the rates and reasons for emergency department visits and hospital
      admissions at an academic tertiary care medical center for HIV/HCV coinfected
      patients as compared to HIV-1 monoinfected patients, using a retrospective
      matched cohort study design. HIV/HCV coinfected patients had higher rates of
      health care utilization (emergency department visits 43.9 versus 7.1 per 100
      person-years; hospital admissions 18.2 versus 6.7 per 100 person-years, for HIV
      coinfected and monoinfected, respectively). This increase was not solely due to
      liver related events. Instead, comorbidities such as diabetes, renal disease, and
      psychiatric/substance abuse played a larger role in the health-care utilization
      in the HIV/HCV coinfected population.

PMID- 22860999
TI  - Aerosolized delivery of oxime MMB-4 in combination with atropine sulfate protects
      against soman exposure in guinea pigs.
AB  - We evaluated the efficacy of aerosolized acetylcholinesterase (AChE) reactivator
      oxime MMB-4 in combination with the anticholinergic atropine sulfate for
      protection against respiratory toxicity and lung injury following
      microinstillation inhalation exposure to nerve agent soman (GD) in guinea pigs.
      Anesthetized animals were exposed to GD (841 mg/m(3), 1.2 LCt(50)) and treated
      with endotracheally aerosolized MMB-4 (50 umol/kg) plus atropine sulfate (0.25
      mg/kg) at 30 sec post-exposure. Treatment with MMB-4 plus atropine increased
      survival to 100% compared to 38% in animals exposed to GD. Decreases in the pulse
      rate and blood O(2) saturation following exposure to GD returned to normal levels
      in the treatment group. The body-weight loss and lung edema was significantly
      reduced in the treatment group. Similarly, bronchoalveolar cell death was
      significantly reduced in the treatment group while GD-induced increase in total
      cell count was decreased consistently but was not significant. GD-induced
      increase in bronchoalveolar protein was diminished after treatment with MMB-4
      plus atropine. Bronchoalveolar lavage AChE and BChE activity were significantly
      increased in animals treated with MMB-4 plus atropine at 24 h. Lung and diaphragm
      tissue also showed a significant increase in AChE activity in the treatment
      group. Treatment with MMB-4 plus atropine sulfate normalized various respiratory
      dynamics parameters including respiratory frequency, tidal volume, peak
      inspiratory and expiratory flow, time of inspiration and expiration, enhanced
      pause and pause post-exposure to GD. Collectively, these results suggest that
      aerosolization of MMB-4 plus atropine increased survival, decreased respiratory
      toxicity and lung injury following GD inhalation exposure.

PMID- 22861000
TI  - Transcriptomics analysis of lungs and peripheral blood of crystalline silica
      exposed rats.
AB  - Minimally invasive approaches to detect/predict target organ toxicity have
      significant practical applications in occupational toxicology. The potential
      application of peripheral blood transcriptomics as a practical approach to study
      the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were
      exposed by inhalation to crystalline silica (15 mg/m(3), 6 h/day, 5 days) and
      pulmonary toxicity and global gene expression profiles of lungs and peripheral
      blood were determined at 32 weeks following termination of exposure. A
      significant elevation in bronchoalveolar lavage fluid lactate dehydrogenase
      activity and moderate histological changes in the lungs, including type II
      pneumocyte hyperplasia and fibrosis, indicated pulmonary toxicity in the rats.
      Similarly, significant infiltration of neutrophils and elevated monocyte
      chemotactic protein-1 levels in the lungs showed pulmonary inflammation in the
      rats. Microarray analysis of global gene expression profiles identified
      significant differential expression [>1.5-fold change and false discovery rate
      (FDR) p < 0.01] of 520 and 537 genes, respectively, in the lungs and blood of the
      exposed rats. Bioinformatics analysis of the differentially expressed genes
      demonstrated significant similarity in the biological processes, molecular
      networks, and canonical pathways enriched by silica exposure in the lungs and
      blood of the rats. Several genes involved in functions relevant to silica-induced
      pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular
      movement, fibrosis, etc, were found significantly differentially expressed in the
      lungs and blood of the silica-exposed rats. The results of this study suggested
      the potential application of peripheral blood gene expression profiling as a
      toxicologically relevant and minimally invasive surrogate approach to study the
      mechanisms underlying silica-induced pulmonary toxicity.

PMID- 22861001
TI  - Size of submicrometric and nanometric particles affect cellular uptake and
      biological activity of macrophages in vitro.
AB  - BACKGROUND: Micrometric and nanometric particles are increasingly used in
      different fields and may exhibit variable toxicity levels depending on their
      physicochemical characteristics. The aim of this study was to determine the
      impact of the size parameter on cellular uptake and biological activity, working
      with well-characterized fluorescent particles. We focused our attention on
      macrophages, the main target cells of the respiratory system responsible for the
      phagocytosis of the particles. METHODS: FITC fluorescent silica particles of
      variable submicronic sizes (850, 500, 250 and 150 nm) but with similar surface
      coating (COOH) were tailored and physico-chemically characterized. These
      particles were then incubated with the RAW 264.7 macrophage cell line. After
      microscopic observations (SEM, TEM, confocal), a quantitative evaluation of the
      uptake was carried out. Fluorescence detected after a quenching with trypan blue
      allows us to distinguish and quantify entirely engulfed fluorescent particles
      from those just adhering to the cell membrane. Finally, these data were compared
      to the in vitro toxicity assessed in terms of cell damage, inflammation and
      oxidative stress (evaluated by LDH release, TNF-alpha and ROS production
      respectively). RESULTS AND CONCLUSION: Particles were well characterized
      (fluorescence, size distribution, zeta potential, agglomeration and surface
      groups) and easily visualized after cellular uptake using confocal and electron
      microscopy. The number of internalized particles was precisely evaluated. Size
      was found to be an important parameter regarding particles uptake and in vitro
      toxicity but this latter strongly depends on the particles doses employed.

PMID- 22861002
TI  - Exposure to arsenic in urban and rural areas and effects on thyroid hormones.
AB  - CONTEXT: Arsenic is a ubiquitous element present in urban air as a pollutant, and
      it may interfere with thyroid hormones. OBJECTIVE: To evaluate the association
      between the personal exposure to arsenic and levels of TSH, fT4, fT3, and Tg in
      urban and rural workers. MATERIALS AND METHODS: Total urinary arsenic and thyroid
      markers were obtained from 108 non-smoking traffic policemen and 77 subjects
      working as roadmen in a rural area. Fifty subjects were monitored to evaluate
      airborne exposure to arsenic. RESULTS: The mean value of exposure to arsenic was
      2.9 ug/m(3) in traffic policemen, while the mean value was less than 0.1 ug/m(3)
      in roadmen. The mean values of urinary arsenic (10.4 MUg/g creatinine vs. 5.2
      MUg/g creatinine; p = 0.000), TSH (1.6 ulU/ml vs. 1.3 ulU/ml; p = 0.006), fT3
      (3.5 pg/ml vs. 3.7 pg/ml; p = 0.000), fT4 (1.2 ng/dl vs. 1.3 ng/dl; p = 0.000)
      and Tg (42.8 ng/ml vs. 36.1 ng/ml; p = 0.04) were significantly different between
      traffic policemen and roadmen. In traffic policemen, urinary arsenic and arsenic
      in the air were correlated to the airborne arsenic and TSH values, respectively.
      Urinary arsenic was correlated to TSH, Tg, fT3, and fT4 values. The multiple
      linear regression models showed the following associations: i) among urinary
      arsenic, arsenic in the air and job title; ii) among TSH, fT3, Tg and urinary
      arsenic; and iii) between fT4 and both urinary arsenic and alcohol intake.
      CONCLUSION: These results provide information about the relationship between
      exposure to arsenic and thyroid markers and may be useful for other categories of
      outdoor workers who are similarly exposed.

PMID- 22861004
TI  - Nurses' turnover: reviewing the evidence, heeding the results?

PMID- 22861003
TI  - Effect of nanoparticle-rich diesel exhaust on testosterone biosynthesis in adult
      male mice.
AB  - The effect of nanoparticle-rich diesel exhaust (NR-DE) on the testicular function
      and factors related with the biosynthesis of testosterone gene expression were
      investigated in mice. Male C57BL/Jcl mice were exposed to clean air, low-dose NR
      DE (Low NR-DE), high-dose NR-DE (High NR-DE) or filtered diesel exhaust (F-DE)
      for 8 weeks. We found that the mice exposed to High NR-DE had significantly
      higher testosterone levels than those in the control and F-DE groups. To
      determine the effects of NR-DE on testicular testosterone production,
      interstitial cells dissected from the male mice which were exposed to NR-DE, F
      DE, or clean air for 8 weeks were incubated with or without human chorionic
      gonadotropin (hCG; 0.1 IU/mL) for 4 h. The concentrations of testosterone in the
      culture media were measured. The testosterone production was significantly
      increased in with or without hCG of High NR-DE exposed group, and significantly
      decreased in both with or without hCG of F-DE exposed groups. Moreover, several
      genes, which is associated with testicular cholesterol synthesis, HMG-CoA, LDL-R,
      SR-B1, PBR, and P450scc, P450 17alpha, and 17beta-HSD were determined in the
      testis of adult male mice. The results showed High NR-DE exposure significantly
      increased the expression of these genes. Whereas, the levels in the F-DE exposure
      group returned to those in the control group, implicating that the nanoparticles
      in DE contribute to the observed reproductive toxicity. We conclude that
      enhancement of testosterone biosynthesis by NR-DE exposure may be regulated by
      increasing testicular enzymes of testosterone biosynthesis.

PMID- 22861005
TI  - Management of difficult suspension laryngoscopy using a GlideScope(r) Video
      Laryngoscope.
AB  - CONCLUSIONS: The GlideScope(r) Video Laryngoscope (GVL) provides a successful
      method for obtaining adequate visualization of the larynx in patients with
      difficult laryngeal exposure (DLE). Although the GVL is far from an ideal
      laryngoscope for laryngeal surgery because of its low image quality and narrow
      curved operation space, valuable concepts regarding its development can be used
      for designing a new laryngoscope specifically for otolaryngology. OBJECTIVE: DLE
      is a problem characterized by poor visualization of the larynx due to a
      combination of anatomic and clinical conditions. With respect to DLE, no
      consensus has been reached as to which alternative method should be used when
      direct laryngoscopy fails. This study focused on the management of DLE cases
      using the GVL to achieve adequate laryngeal exposure for phonosurgery. METHODS:
      We used the GVL in conjunction with a set of specially designed endolaryngeal
      instruments in six cases for which traditional rigid laryngoscopy could not
      provide visualization of the larynx. RESULTS: Using the GVL, full visualization
      of the larynx was obtained in all patients with minimal need for excessive
      internal or external pressure. Manipulations to remove simple lesions or perform
      a biopsy were carried out successfully. All of the surgeries were completed with
      excellent visualization and without any major complications.

PMID- 22861006
TI  - Design, synthesis and functional analysis of dansylated polytheonamide mimic: an
      artificial peptide ion channel.
AB  - We report herein the design, total synthesis, and functional analysis of a novel
      artificial ion channel molecule, designated as dansylated polytheonamide mimic
      (3). The channel 3 was designed based on an exceptionally potent cytotoxin,
      polytheonamide B (1). Our strategy for the development of synthetic ion channels,
      which could be easily derivatized for various functions, involved two key
      features. First, the structure of 1 was simplified by replacing many of
      nonproteinogenic amino acid residues which required multistep synthesis by
      commercially available amino acids while retaining those residues necessary for
      folding. It significantly reduced the number of synthetic steps and facilitated a
      practical chemical construction of 3. Second, the introduction of propargyl
      glycine at residue 44 enabled facile installation of dansyl group as a reporter
      of the membrane localization of 3. Application of a newly designed protective
      group strategy provided efficient construction of the 37 amino acid sequence of
      residues 12-48 through one automatic solid-phase peptide synthesis. After peptide
      cleavage from the resin, 3 was synthesized via dansyl group introduction and one
      fragment-coupling reaction with residues 1-11, followed by the global
      deprotection. The simplified mimic 3 exhibited potent cytotoxicity toward p388
      mouse leukemia cells (IC(50) = 12 nM), effectively induced ion transport across
      the lipid bilayers of liposomes, and displayed H(+) and Na(+) ion channel
      activities. Because of its simplified yet functional scaffold structure with a
      potential for diversification, our rationally designed ion channel molecule
      should be useful as a novel platform for developing various cytotoxic channel
      molecules with additional desired functions.

PMID- 22861007
TI  - A new form of cerebral folate deficiency with severe self-injurious behaviour.

PMID- 22861008
TI  - DNA charge transport for sensing and signaling.
AB  - The DNA duplex is an exquisite macromolecular array that stores genetic
      information to encode proteins and regulate pathways. Its unique structure also
      imparts chemical function that allows it also to mediate charge transport (CT).
      We have utilized diverse platforms to probe DNA CT, using spectroscopic,
      electrochemical, and even genetic methods. These studies have established
      powerful features of DNA CT chemistry. DNA CT can occur over long molecular
      distances as long as the bases are well stacked. The perturbations in base
      stacking that arise with single base mismatches, DNA lesions, and the binding of
      some proteins that kink the DNA all inhibit DNA CT. Significantly, single
      molecule studies of DNA CT show that ground state CT can occur over 34 nm if the
      duplex is well stacked; one single base mismatch inhibits CT. The DNA duplex is
      an effective sensor for the integrity of the base pair stack. Moreover, the
      efficiency of DNA CT is what one would expect for a stack of graphite sheets:
      equivalent to the stack of DNA base pairs and independent of the sugar-phosphate
      backbone. Since DNA CT offers a means to carry out redox chemistry from a
      distance, we have considered how this chemistry might be used for long range
      biological signaling. We have taken advantage of our chemical probes and
      platforms to characterize DNA CT in the context of the cell. CT can occur over
      long distances, perhaps funneling damage to particular sites and insulating
      others from oxidative stress. Significantly, transcription factors that activate
      the genome to respond to oxidative stress can also be activated from a distance
      through DNA CT. Numerous proteins maintain the integrity of the genome and an
      increasing number of them contain [4Fe-4S] clusters that do not appear to carry
      out either structural or enzymatic roles. Using electrochemical methods, we find
      that DNA binding shifts the redox potentials of the clusters, activating them
      towards oxidation at physiological potentials. We have proposed a model that
      describes how repair proteins may utilize DNA CT to efficiently search the genome
      for lesions. Importantly, many of these proteins occur in low copy numbers within
      the cell, and thus a processive mechanism does not provide a sufficient
      explanation of how they find and repair lesions before the cell divides. Using
      atomic force microscopy and genetic assays, we show that repair proteins
      proficient at DNA CT can relocalize in the vicinity of DNA lesions and can
      cooperate in finding lesions within the cell. Conversely, proteins defective in
      DNA CT cannot relocalize in the vicinity of lesions and do not assist other
      proteins involved in repair within the cell. Moreover such genetic defects are
      associated with disease in human protein analogues. As we continue to unravel
      this chemistry and discover more proteins with redox cofactors involved in genome
      maintenance, we are learning more regarding opportunities for long range
      signaling and sensing, and more examples of DNA CT chemistry that may provide
      critical functions within the cell.

PMID- 22861009
TI  - RNA-sequencing as useful screening tool in the combat against the misuse of
      anabolic agents.
AB  - The abuse of anabolic substances in animal husbandry is forbidden within the EU
      and well controlled by detecting substance residues in different matrices. The
      application of newly designed drugs or substance cocktails represents big
      problems. Therefore developing sensitive test methods is important. The analysis
      of physiological changes caused by the use of anabolic agents on the molecular
      level, for example, by quantifying gene expression response, is a new approach to
      develop such screening methods. A novel technology for holistic gene expression
      analysis is RNA sequencing. In this study, the potential of this high-throughput
      method for the identification of biomarkers was evaluated. The effect of
      trenbolone acetate plus estradiol on gene expression in liver from Nguni heifers
      was analyzed with RNA sequencing. The expression of 40 selected candidate genes
      was verified via RT-qPCR, whereby 20 of these genes were significantly regulated.
      To extract the intended information from these regulated genes, biostatistical
      tools for pattern recognition were applied and resulted in a clear separation of
      the treatment groups. Those candidate genes could be verified in boars and in
      calves treated with anabolic substances. These results show the potential of RNA
      sequencing to screen for biomarker candidates to detect the abuse of anabolics.
      The verification of these biomarkers in boars and calves leads to the assumption
      that gene expression biomarkers are independent of breed or even species and that
      biomarkers, identified in farm animals could also act as potential biomarker
      candidates to detect the abuse of anabolic substances in human sports.

PMID- 22861047
TI  - Translumenal esophageal anastomosis for natural orifice translumenal endoscopic
      surgery: an ex vivo feasibility study.
AB  - AIM: This study aimed to develop a novel procedure for esophagoesophageal
      anastomosis for natural orifice translumenal endoscopic surgery (NOTES).
      MATERIALS AND METHODS: An ex vivo feasibility study was performed in eight
      porcine models. The procedure was as follows: (1) A BraceBarTM (Olympus Medical
      Systems Corp., Tokyo, Japan), a double T-bar suturing device, was placed
      endoscopically at the blind end of the upper esophagus (UE). (2) The blind end
      was incised, and the scope was advanced out of the esophagus. (3) A balloon
      catheter was inserted into the lower esophagus (LE). (4) The catheter and a
      thread on the BraceBar were withdrawn so that the end of the UE was inverted, and
      the LE was pulled into the UE. (5) After the catheter was removed, a short tube
      was placed inside the duplicated part of the esophagus via the transgastric
      route. (6) A double ligature was performed using a ligating device over the tube.
      A liquid leak test was performed after the procedure. RESULTS: All steps in this
      procedure were technically successful under the endoscopic visualization without
      any assistance from outside of the esophagus. The median time of this procedure
      was 31 (23-66) minutes. The median internal pressure of the UE was 122 (82-142)
      mm Hg when the anastomosed esophagus was separated into two specimens during the
      leak test. CONCLUSIONS: Translumenal esophagoesophageal anastomosis was feasible.
      The duration of the procedure was short, and the anastomoses appear to have
      sufficient strength for use in clinical practice. An in vivo survival study is
      needed to confirm the safety and reliability of this NOTES procedure.

PMID- 22861048
TI  - Biosynthetic pathway for high structural diversity of a common dilactone core in
      antimycin production.
AB  - We herein report comparative analysis of two versions of the biosynthetic gene
      clusters of antimycins, a natural product family possessing up to 44 distinct
      entities. The biosynthetic pathway of antimycins is amenable to the high
      structural variation of the substrates, supported by successes in heterologous
      expression of the ant cluster and in fluorine incorporation. The latter
      facilitated the investigation of the structure-activity relationship into the
      usually invariable 3-formamidosalicylic acid moiety of the molecules.

PMID- 22861049
TI  - Ventricular septal defect in a ferret (Mustela putorius furo).
AB  - A four-year-old, castrated male ferret (Mustela putorius furo) was evaluated
      because of a one-year history of sporadic cough. On physical examination a grade
      5 of 6 holosystolic murmur was audible over the right apex of the heart.
      Radiographic findings included the presence of air bronchograms in apical lobes
      accompanied by pulmonary venous congestion. Colour Doppler echocardiography
      revealed a left-to-right shunting compatible with a ventricular septal defect.
      Medical therapy was initiated at the time of the diagnosis. The ferret was
      presented again 2 months after the initial examination for coughing and
      respiratory distress. Echocardiographic findings included tricuspid
      regurgitation, relative enlargement of left-atrial diameter and decreased
      systolic function, with presence of pleural effusion. Thoracocentesis was
      performed and the therapeutic plan was revised. In the following months the
      symptoms did not recur. In the authors' opinion this is the first report to
      describe the clinical findings of isolated ventricular septal defect in the
      ferret. Congenital heart defects are rare in this species, the present ferret
      being only the second case described.

PMID- 22861050
TI  - Infants use compression information to infer objects' weights: examining
      cognition, exploration, and prospective action in a preferential-reaching task.
AB  - The present research used a preferential-reaching task to examine whether 9- and
      11-month-olds (n=144) could infer the relative weights of two objects resting on
      a soft, compressible platform. Experiment 1 established that infants reached
      preferentially for the lighter of 2 boxes. In Experiments 2-4, infants saw 2
      boxes identical except in weight resting on a cotton wool platform. Infants
      reached prospectively for the lighter box, but only when their initial
      exploratory activities provided critical information. At 11 months, infants
      succeeded as long as they first determined that the platform was compressible; at
      9 months, infants succeeded only if they also explored the boxes and thus had
      advance knowledge that they differed in weight.

PMID- 22861051
TI  - The development of academic geriatric medicine in the United States 2005 to 2010:
      an essential resource for improving the medical care of older adults.
AB  - Academic geriatric medicine programs are critical for training the physician
      workforce to care effectively for aging Americans. This article updates the
      progress made by U.S. medical schools from 2005 to 2010 in developing these
      programs. Academic leaders in geriatrics in accredited allopathic and osteopathic
      medical schools were surveyed in the winter of 2010 (60% response rate), and
      results were compared with findings from a similar 2005 survey (68% response
      rate). Physician faculty in geriatrics increased from 9.6 (mean) full-time
      equivalents (FTEs) in 2005 to 11.2 by 2010. In 2010, faculty and staff effort was
      mostly devoted to clinical practice (mean = 37%) and education (mean = 33%), with
      only seven responding schools devoting more than 40% of faculty effort to
      research. Schools that have been designated as Centers of Excellence had a median
      20 FTE physician faculty, compared with seven at the other schools (P < .001). In
      2010, 27% of medical schools required a geriatrics clerkship, and 87% (n = 83)
      had an elective geriatric clerkship. In summary, more fellows and faculty were
      recruited and trained in 2010 than in 2005, and some academic programs have
      emerged with strong education, research, and clinical initiatives. Medical
      student exposure to geriatrics curriculum has increased, but few academic
      geriatricians are pursuing research careers, and the number of practicing
      geriatricians is declining. New approaches to training the entire physician
      workforce to care for older adults will be required to ensure adequate medical
      care for aging Americans.

PMID- 22861053
TI  - Perceptions of the benefits and challenges of the role of advanced practice
      nurses in nurse-led out-of-hours care in Hong Kong: a questionnaire study.
AB  - AIMS AND OBJECTIVES: The aim of the study was to identify the factors that nurses
      perceive may facilitate or hinder the development of advanced practice nurse
      roles in Hong Kong. BACKGROUND: Advanced practice nurses are increasingly
      prominent in nurse-led out-of-hours care in Hong Kong in response to changes to
      junior doctors' hours of work. SETTING: Three five-day workshops for Hong Kong
      based advanced practice nurses were offered in partnership with UK clinicians.
      The aim of the workshops was to share UK experiences of implementation of the
      'Hospital at Night' model of care delivery. The questionnaire study undertaken
      was not part of the workshop programme. However, the workshops gave the authors a
      unique opportunity to access relatively large numbers of Hong Kong-based advanced
      practice nurses. PARTICIPANTS: The workshops were attended by experienced nurses
      who had been or were about to be appointed as advanced practice nurses. All
      nurses who attended one of the three workshops (n=120) agreed to participate in
      the study. METHODS: Responses to two open questions posed in the questionnaire
      were the subject of a content analysis. RESULTS: A prominent finding of the study
      was that respondents viewed the benefits of introducing advanced practice nurse
      roles in Hong Kong as outweighing any challenges. One of the main features of the
      perceived benefits relates to improving the quality and safety of patient care.
      The greatest challenges associated with the role related to acceptance of the
      role by other healthcare professionals, and difficulties associated with the
      general public's traditional attitudes to healthcare provision in Hong Kong.
      CONCLUSIONS: Education of the public concerning the implementation of such roles
      is of crucial importance. RELEVANCE TO CLINICAL PRACTICE: Findings from this
      study enhance understanding of the factors that hinder or facilitate advanced
      practice roles in out-of-hours care in Hong Kong.

PMID- 22861054
TI  - Developing a new hybrid revascularization program: a road map for hospital
      managers and physician leaders.
AB  - Hybrid coronary revascularization, which involves minimally invasive direct
      coronary artery bypass surgery using the left internal mammary artery to left
      anterior descending and percutaneous coronary intervention using drug-eluting
      stents for the remaining diseased coronary vessels, is an innovative approach to
      decrease the morbidity of conventional surgery. Little information is available
      to guide hospital managers and physician leaders in implementing a hybrid
      revascularization program. In this article, we describe the people-process
      technology issues that managers and leaders are likely to encounter as they
      develop a hybrid revascularization program in their practice.

PMID- 22861052
TI  - New hepatitis C virus drug discovery strategies and model systems.
AB  - INTRODUCTION: Hepatitis C virus (HCV) is a major cause of liver disease worldwide
      and the leading indication for liver transplantation in the United States.
      Current treatment options are expensive, not effective in all patients and are
      associated with serious side effects. Although preclinical, anti-HCV drug
      screening is still hampered by the lack of readily infectable small animal
      models, the development of cell culture HCV experimental model systems has driven
      a promising new wave of HCV antiviral drug discovery. AREAS COVERED: This review
      contains a concise overview of current HCV treatment options and limitations with
      a subsequent in-depth focus on the available experimental models and novel
      strategies that have, and continue to enable, important advances in HCV drug
      development. EXPERT OPINION: With a large cohort of chronically HCV-infected
      patients progressively developing liver disease that puts them at risk for
      hepatocellular carcinoma and hepatic decompensation, there is an urgent need to
      develop effective therapeutics that are well tolerated and effective in all
      patients and against all HCV genotypes. Significant advances in HCV experimental
      model development have expedited drug discovery; however, additional progress is
      needed. Importantly, the current trends and momentum in the field suggests that
      we will continue to overcome critical experimental challenges to reach this end
      goal.

PMID- 22861055
TI  - Regulation of hepatic insulin sensitivity by activating signal co-integrator-2.
AB  - ASC-2 (activating signal co-integrator-2, also known as AIB3 and NCoA6) is a
      transcriptional co-activator and regulates insulin secretion and beta-cell
      survival. The present study was performed to elucidate the role of ASC-2 in the
      regulation of insulin sensitivity. Although islet cells from 10-week-old ASC-2+/-
      mice secreted less insulin than wild-type islets, there was no significant
      difference in glucose tolerance between ASC-2+/- and wild-type mice. However, ASC
      2+/- mice did show increased insulin sensitivity compared with wild-type mice in
      insulin tolerance tests. Consistently, the levels of phosphorylated Akt were
      higher in ASC-2+/- hepatocytes than in wild-type hepatocytes after insulin
      treatment. Moreover, decreases in phosphoenol pyruvate carboxykinase mRNA in
      refed mice were more prominent in ASC-2+/- livers than in wild-type livers.
      Interestingly, the expression levels of SOCS1 (suppressor of cytokine signalling
      1) and SOCS3, well-known insulin signalling inhibitors, were decreased in ASC-2+/
      hepatocytes and increased in ASC-2-overexpressing hepatocytes. Furthermore, ASC
      2 was recruited to the promoter region of SOCS1 and potentiated the transcription
      by SREBP-1c (sterol-regulatory-element-binding protein-1c). This transcription
      activating function of ASC-2 was diminished by mutations of SREBP-1c-binding
      sites in the SOCS1 promoter. Taken together, these results suggest that ASC-2
      negatively affects hepatic insulin sensitivity, at least in part, through
      induction of the insulin signalling inhibitors SOCS1 and SOCS3.

PMID- 22861056
TI  - Impact of processing on the noncovalent interactions between procyanidin and
      apple cell wall.
AB  - Procyanidins can bind cell wall material in raw product, and it could be supposed
      that the same mechanism of retention of procyanidins by apple cell walls takes
      place in cooked products. To evaluate the influence of cell wall composition and
      disassembly during cooking on the cell walls'  capacity to interact with
      procyanidins, four cell wall materials differing in their protein contents and
      physical characteristics were prepared: cell wall with proteins, cell wall devoid
      of protein, and two processed cell walls differing by their drying method.
      Protein contents varied from 23 to 99 mg/g and surface areas from 1.26 to 3.16
      m(2)/g. Apple procyanidins with an average polymerization degree of 8.7 were
      used. The adsorption of apple procyanidins on solid cell wall material was
      quantified using the Langmuir isotherm formulation. The protein contents in cell
      wall material had no effect on procyanidin/cell wall interactions, whereas
      modification of the cell wall material by boiling, which reduces pectin content,
      and drying decreased the apparent affinity and increased the apparent saturation
      levels when constants were expressed relative to cell wall weight. However,
      boiling and drying increased apparent saturation levels and had no effect on
      apparent affinity when the same data were expressed per surface units. Isothermal
      titration calorimetry indicated strong affinity (K(a) = 1.4 * 10(4) M(-1))
      between pectins solubilized by boiling and procyanidins. This study higllights
      the impact of highly methylated pectins and drying, that is, composition and
      structure of cell wall in the cell wall/procyanidin interactions.

PMID- 22861057
TI  - Commentary: treatment of venous infraorbital dark circles using a long-pulsed
      1,064-nm neodymium-doped yttrium aluminum garnet laser.

PMID- 22861058
TI  - Commentary: fractional laser resurfacing to enhance skin permeation.

PMID- 22861059
TI  - Enhanced removal of phenol with saline solution over alcohol: an in vitro study.
AB  - BACKGROUND: Phenol cauterization is a chemical equivalent often chosen for
      treatment of ingrown toenails. Many reports describe intraoperative irrigation,
      or lavage, of the wound with various types of alcohol to neutralize any remaining
      phenol. There are conflicting reports in the literature as to whether true
      neutralization or merely effective removal of excess phenol is needed. OBJECTIVE:
      The aim of our study was to analyze the suitability and effectiveness of ethyl
      alcohol versus sterile saline when used in a lavage step after phenol application
      in the treatment of ingrown toenails. METHODS: We performed an in vitro study
      using human skin and a diffusion cell apparatus to measure the amount of phenol
      recovered after lavage with ethyl alcohol or sterile saline. RESULTS: When the
      wound was irrigated with ethyl alcohol, the total phenol recovered after two
      irrigation washes was 55.7% of the original amount initially used in treatment,
      compared with 80.4% when sterile saline solution was used for irrigation.
      CONCLUSION: Alcohol and sterile saline solution do not neutralize phenol but
      dilute it and aid in its removal. We found that saline solution recovered more
      phenol than when washing with alcohol and recommend its use instead of alcohol
      for irrigation purposes after chemical matrixectomy.

PMID- 22861060
TI  - Commentary: optimal staining of frozen sections: a conundrum.

PMID- 22861061
TI  - Commentary: diagnostic utility of cytokeratin 17 immunostaining in morpheaform
      basal cell carcinoma and for facilitating the detection of tumor cells at the
      surgical margins.

PMID- 22861062
TI  - Letter: comment on letter to the editor.

PMID- 22861063
TI  - Letter: onychocryptosis of the toenail: the effectiveness of surgical
      matricectomy.

PMID- 22861064
TI  - Letter regarding "Enhanced port-wine stain lightening achieved with combined
      treatment of selective photothermolysis and imiquimod".

PMID- 22861065
TI  - Targeting neuroinflammation for therapeutic intervention in neurodegenerative
      pathologies: a role for the peptide analogue of thymulin (PAT).
AB  - INTRODUCTION: Inflammation has a vital task in protecting the organism, but when
      deregulated, it can have serious pathological consequences. The central nervous
      system (CNS) is capable of mounting immune and inflammatory responses, albeit
      different from that observed in the periphery. Neuroinflammation, however, can be
      a major contributor to neurodegenerative diseases and constitute a major
      challenge for medicine and basic research. AREAS COVERED: Both innate and
      adaptive immune responses normally play an important role in homeostasis within
      the CNS. Microglia, astrocytes and neuronal cells express a wide array of toll
      like receptors (TLR) that can be upregulated by infection, trauma, injuries and
      various exogenic or endogenic factors. Chronic hyper activation of brain immune
      cells can result in neurotoxic actions due to excessive production of several pro
      inflammatory mediators. Several studies have recently described an important role
      for targeting receptors such as nicotinic receptors located on cells in the CNS
      or in other tissues for the control of inflammation. EXPERT OPINION: Thymulin and
      its synthetic peptide analogue (PAT) appear to exert potent anti-inflammatory
      effects at the level of peripheral tissues as well as at the level of the brain.
      This effect involves, at least partially, the activation of cholinergic
      mechanisms.

PMID- 22861067
TI  - Formation of multilayers by star polyelectrolytes: effect of number of arms on
      chain interpenetration.
AB  - We have investigated the influence of number of arms on chain interpenetration in
      the growth of star poly[2-(dimethylamino)ethyl methacrylate] (PDEM)/star
      poly(acrylic acid) (PAA) multilayers using a quartz crystal microbalance with
      dissipation (QCM-D). The oscillations in the changes of dissipation and frequency
      reflect the chain interpenetration and the variation of the mass of multilayer,
      respectively. The QCM-D results demonstrate that the growth of multilayers has
      two different mechanisms in terms of chain interpenetration. That is, the arm
      chains of star PDEM insert into a predeposited PAA layer to form a swollen
      multilayer, but the complex of star PAA with predeposited star PDEM is an
      "octopus-like" structure forming a dense multilayer. The transition between these
      two penetration modes is controlled by the number of arms in the star
      polyelectrolytes. As the number of arms of either PAA or PDEM increases, it
      becomes more difficult for star PDEM to penetrate into the PAA layer, but star
      PAA can more easily penetrate into the PDEM layer. According to atomic force
      microscopy and water contact angle measurements, all eight-bilayer multilayer
      surfaces have similar roughness values, and the surface wettability of the
      multilayers is dominated by the outermost PDEM layer.

PMID- 22861066
TI  - Synthesis and NMR characterization of (Z,Z,Z,Z,E,E,omega)-heptaprenol.
AB  - We describe a practical, multigram synthesis of (2Z,6Z,10Z,14Z,18E,22E)
      3,7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-ol
      [(Z(4),E(2),omega)-heptaprenol, 4] using the nerol-derived sulfone 8 as the key
      intermediate. Sulfone 8 is prepared by the literature route and is converted in
      five additional steps (18% yield from 8) to (Z(4),E(2),omega)-heptaprenol 4. The
      use of Eu(hfc)(3) as an NMR shift reagent not only enabled confirmation of the
      structure and stereochemistry of 4, but further enabled the structural assignment
      to a major side product from a failed synthetic connection. The availability by
      this synthesis of (Z(4),E(2),omega)-heptaprenol 4 in gram quantities will enable
      preparative access to key reagents for the study of the biosynthesis of the
      bacterial cell envelope.

PMID- 22861068
TI  - Actinic keratosis in the en-face and slice imaging mode of high-definition
      optical coherence tomography and comparison with histology.
AB  - BACKGROUND: Optical coherence tomography (OCT) allows real-time, in vivo
      examination of nonmelanoma skin cancer. An innovative high-definition (HD)-OCT
      with a horizontal (en-face) and vertical (slice) imaging mode offers additional
      information in the diagnosis of actinic keratosis (AK) and may potentially
      replace invasive diagnostic biopsies. OBJECTIVES:  To define the characteristic
      morphological features of AK by using HD-OCT in the two imaging modes compared
      with histopathology as gold standard. METHODS:  In total, 20 AKs were examined by
      HD-OCT in the en-face and slice imaging modes and characteristic features were
      described and evaluated in comparison with the histopathological findings.
      Furthermore, the HD-OCT images of a subgroup of AKs were compared with those of
      the clinically normal adjacent skin. RESULTS:  The preoperative in vivo
      diagnostics showed the following features in the en-face imaging mode of HD-OCT:
      disruption of stratum corneum, architectural disarray, cellular/nuclear
      polymorphism in the stratum granulosum/stratum spinosum, and bright irregular
      bundles in the superficial dermis. In the vertical slice imaging mode the
      following characteristics were found: irregular entrance signal, destruction of
      layering, white streaks and dots, and grey areas. In contrast, the clinically
      healthy adjacent skin showed mainly a regular epidermal 'honeycomb' pattern in
      the en-face mode and distinct layering of the skin in the slice mode.
      CONCLUSIONS:  HD-OCT with both the en-face and slice imaging modes offers
      additional information in the diagnosis of AK compared with conventional OCT and
      might enhance the possibility of the noninvasive diagnosis of AK prior to
      treatment procedures and possibly in the monitoring of noninvasive treatment
      strategies.

PMID- 22861069
TI  - The relationship between emotional-state language and emotion understanding: a
      study with school-age children.
AB  - We carried out an investigation with primary-school children on the relationship
      between both use and comprehension of emotional-state language and emotion
      understanding. Participants were 100 students between 7 and 10 years old (mean
      age=8 years and 10 months; SD=15.3 months), equally divided by gender. They
      completed four tests evaluating their language ability, use of emotional-state
      language, comprehension of emotional-state language and emotion understanding
      (EU) respectively. Significant correlations were found between both use and
      comprehension of emotional-state talk and children's EU. In addition, regression
      analyses showed that comprehension of emotional-state language, rather than its
      use, plays a significant role in explaining children's emotion understanding.

PMID- 22861070
TI  - Review of metabolic, immunologic, and virologic consequences of suboptimal
      vitamin D levels in HIV infection.
AB  - Low 25-hydroxyvitamin D levels are common in the general and HIV-infected
      populations alike. Defined as levels less than 30 ng/mL, suboptimal vitamin D is
      known to afflict over 70% of representative samples from each group in resource
      rich countries with even greater prevalence in resource-poor regions of the
      world. In both those with and without HIV, dark skin, low vitamin D intake,
      exiguous exposure to sunlight, and season act as risk factors for suboptimal
      vitamin D levels. In those infected with HIV, antiretroviral therapy,
      particularly non-nucleoside reverse transcriptase inhibitors (NNRTIs), increase
      risk for low vitamin D as well. Furthermore, metabolic aberrations, including
      obesity and hyperlipidemia, and miscellaneous risk factors, such as advanced AIDS
      and substance abuse, have been linked to suboptimal vitamin D in those with HIV.
      While the skeletal and cardiovascular systems of HIV patients may be adversely
      impacted as a result of low levels, recent data have also linked low vitamin D to
      decreased CD4 counts, higher viral loads, and to critical end points including
      progression to AIDS events and death. More research is needed to confirm these
      potential consequences of low vitamin D in those with HIV and to discern the
      benefits of routine screening for and treatment of low vitamin D in this
      population.

PMID- 22861071
TI  - A qualitative study of young people's perspectives of living with type 1
      diabetes: do perceptions vary by levels of metabolic control?
AB  - AIM: To explore if young people with higher and lower levels of metabolic control
      of type 1 diabetes have different perceptions about their lives and illness.
      BACKGROUND: Adolescence through emerging adulthood is a developmental stage made
      more challenging when the person has type 1 diabetes. Little research has
      investigated if individuals with high and low levels of metabolic control in this
      age group perceive their disease differently. DESIGN: Qualitative descriptive.
      METHODS: In this study, 14 participants, ages 11-22 years were interviewed in
      2008 about their perceptions of living with type 1 diabetes. Through a process of
      induction, major themes were identified. RESULTS/FINDINGS: Participants with high
      and low metabolic control levels reported similar themes related to reactions of
      others, knowledge about type 1 diabetes, and believed healthcare providers used
      authoritarian interactions. However, high metabolic control level participants
      believed type 1 diabetes would be cured; had negative initial responses to being
      diagnosed; rarely received parental support in managing their diabetes; and were
      negligent in self-care activities. Participants with low metabolic control levels
      did not believe a cure was imminent or have negative responses to being
      diagnosed; received parental support in managing diabetes; and were diligent in
      self-care activities. CONCLUSION: Nurses should give information to young people
      with type 1 diabetes beyond initial diagnosis and help and support this age group
      learn appropriate ways to manage their disease, develop positive relationships
      with healthcare professionals, and participate in interactions with others their
      age successfully managing type 1 diabetes.

PMID- 22861072
TI  - Enhancement in the sensitivity of microfluidic enzyme-linked immunosorbent assays
      through analyte preconcentration.
AB  - In this Article, we describe a microfluidic enzyme-linked immunosorbent assay
      (ELISA) method whose sensitivity can be substantially enhanced through
      preconcentration of the target analyte around a semipermeable membrane. The
      reported preconcentration has been accomplished in our current work via
      electrokinetic means allowing a significant increase in the amount of captured
      analyte relative to nonspecific binding in the trapping/detection zone. Upon
      introduction of an enzyme substrate into this region, the rate of generation of
      the ELISA reaction product (resorufin) was observed to increase by over a factor
      of 200 for the sample and 2 for the corresponding blank compared to similar
      assays without analyte trapping. Interestingly, in spite of nonuniformities in
      the amount of captured analyte along the surface of our analysis channel, the
      measured fluorescence signal in the preconcentration zone increased linearly with
      time over an enzyme reaction period of 30 min and at a rate that was proportional
      to the analyte concentration in the bulk sample. In our current study, the
      reported technique has been shown to reduce the smallest detectable concentration
      of the tumor marker CA 19-9 and Blue Tongue Viral antibody by over 2 orders of
      magnitude compared to immunoassays without analyte preconcentration. When
      compared to microwell based ELISAs, the reported microfluidic approach not only
      yielded a similar improvement in the smallest detectable analyte concentration
      but also reduced the sample consumption in the assay by a factor of 20 (5 MUL
      versus 100 MUL).

PMID- 22861074
TI  - Randomized controlled trial for endoscopy with propofol versus midazolam on
      psychometric tests and critical flicker frequency in people with cirrhosis.
AB  - BACKGROUND AND AIM: People with cirrhosis are at increased risk of development of
      complications related to sedation. The aim of the present study was to compare
      the effects of sedation for upper gastrointestinal endoscopy (UGIE) with propofol
      and midazolam on psychometric tests and critical flicker frequency (CFF) in
      people with cirrhosis. METHODS: A total of 127 people with cirrhosis were
      randomized into three groups: propofol group (n = 40), midazolam group (n = 42)
      and no sedation (n = 45). All patients underwent CFF test and combination of
      psychometry (number connection test-A and B [NCT-A,B]; digit symbol test [DST],
      line tracing test [LTT] and serial dotting test [SDT]) at baseline and at 2 h
      post-endoscopy. CFF was done at 30 min and repeated every 30 min for 2 h.
      RESULTS: In the propofol group there was no deterioration in psychometry (NCT-A
      [55.6 +/- 18.7 vs 56.4 +/- 19.0 s], NCT-B [98.2 +/- 35.1 vs 97.8 +/- 34.6 s], DST
      [26.7 +/- 5.7 vs 26.3 +/- 5.3], LTT [112.9 +/- 35.7 vs 113.7 +/- 36.6 s], SDT
      [94.6 +/- 34.1 vs 95.2 +/- 34.5 s]). Significant deterioration from baseline
      (39.8 +/- 2.9 Hz) was seen in CFF at 30 min (38.8 +/- 2.3 Hz) and 1 h (39.2 +/-
      2.4 Hz), P = 0.01 but no difference thereafter. In the midazolam group,
      significant deterioration was observed on psychometry (NCT-A [56.0 +/- 18.5 vs
      60.4 +/- 19.8 s], NCT-B [99.9 +/- 29.1 vs 105.9.6 +/- 30.3 s], DST [26.1 +/- 4.7
      vs 25.2 +/- 4.3], LTT [129.1 +/- 34.5 vs 132.9 +/- 35.4 s], SDT [95.6 +/- 34.2]).
      No deterioration was observed in psychometry and CFF in people with cirrhosis
      without sedation. CONCLUSIONS: Propofol sedation for UGIE was associated with
      earlier recovery compared with midazolam, which causes deterioration of
      psychometric tests and CFF for a longer time in comparison with propofol.

PMID- 22861075
TI  - One-pot cascade leading to direct alpha-imidation of ketones by a combination of
      N-bromosuccinimide and 1,8-diazabicyclo[5.4.1]undec-7-ene.
AB  - A one-pot cascade transformation of ketones into alpha-imidoketones has been
      developed, in which N-bromosuccinimide (NBS) provides both electrophilic bromine
      and nucleophilic nitrogen sources, and diazabicyclo[5.4.1]undec-7-ene (DBU)
      functions as a base and a nucleophilic promoter for the activation of NBS. alpha
      Bromination is supposed as the key step in the process, which takes place between
      more electrophilic bromide active species and enolates.

PMID- 22861076
TI  - Treatment for postoperative wound pain in gynecologic laparoscopic surgery:
      topical lidocaine patches.
AB  - BACKGROUND: This article reports our early experience with the use of lidocaine
      patches for pain control in the immediate postoperative period after laparoscopic
      gynecologic surgery. SUBJECTS AND METHODS: A prospective, double-blind, placebo
      controlled clinical trial was conducted on 40 patients undergoing a gynecologic
      laparoscopy who were randomized to receive either topical patches of 700 mg of
      lidocaine (n=20) or placebo patches (n=20). The patch was divided evenly into
      four smaller patches, which were applied at the four port sites and changed every
      12 hours for 36 hours after surgery. Postoperative pain was evaluated using the
      visual analog scale (VAS) score and the Prince Henry and 5-point verbal rating
      pain scale (VRS), and the analgesic requirement was also evaluated at 1, 6, 12,
      24, and 36 hours after surgery. RESULTS: The VAS score for wound pain was lower
      in the lidocaine patch group at 1 and 6 hours after surgery than the control
      group (P=.005 and <.0005, respectively). The VAS scores for postoperative pain
      were lower in the lidocaine patch group at rest 1 hour after surgery (P=.045).
      The 5-point VRS score for postoperative pain was lower in the lidocaine patch
      group at 6 and 12 hours after surgery (P=.015 and .035, respectively) than in the
      control group. CONCLUSIONS: Topical lidocaine patches at the laparoscopic port
      sites reduced postoperative pain, particularly postoperative wound pain after
      gynecological laparoscopic procedures.

PMID- 22861077
TI  - Investigation into scatter radiation dose levels received by a restrainer in
      small animal radiography.
AB  - OBJECTIVES: To measure the intensity and distribution of scatter radiation
      received by a restrainer in veterinary radiography including the intensity of
      scatter radiation passing through lead protective devices at pre-defined
      positions. METHODS: Anthropomorphic phantoms and a Labrador dog cadaver were used
      to simulate a restrainer and patient. Scatter dose measurements were recorded at
      the position of the restraining hands, thyroid, breast and gonads with and
      without appropriate lead protection. This was repeated for the eight most common
      projections as identified in an initial retrospective survey. RESULTS: Manual
      restraint of an animal for a radiographic procedure will result in a scatter
      radiation dose to the restrainer. The level of radiation dose varies between body
      regions and between projections. The use of appropriate lead protection resulted
      in statistically significant dose reductions to all body regions with maximum
      scatter dose reductions between 93 and 100%. CLINICAL SIGNIFICANCE: While the
      doses recorded were small (MUGy) in terms of associated risk, they are
      nonetheless cumulative which can result in a more significant dose. Therefore
      manual restraint should be avoided and forms of immobilisation should be used
      such as mechanical means, sedation or general anaesthesia. However, if completely
      necessary both principles of distance and adequate lead protection should be
      employed.

PMID- 22861117
TI  - Toddlers use the number feature in determiners during online noun comprehension.
AB  - Function words support many aspects of language acquisition. This study
      investigated whether toddlers understand the number feature of determiners and
      use it for noun comprehension. French offers an ideal "test case" as number is
      phonetically marked in determiners but not in nouns. Twenty French-learning 24
      month-olds completed a split-screen experiment. Looking times to target pictures
      were measured under 3 trial types varying in the degree to which the determiner
      matched the number displayed in the object(s). Children looked longer when the
      determiner matched the object(s), and were confused in trials of clear mismatch.
      Importantly, their processing resembled that of French adults (D. Dahan, D.
      Swingley, M. K. Tanenhaus, & J. S. Magnuson, 2000). Thus, children understand the
      determiner number feature early in acquisition and use this knowledge to
      constrain online comprehension.

PMID- 22861118
TI  - Comparison of frailty indicators based on clinical phenotype and the multiple
      deficit approach in predicting mortality and physical limitation.
AB  - OBJECTIVES: To compare three simple bedside tools based on frailty phenotypes
      with a Frailty Index using the multiple deficit approach in the prediction of
      mortality and physical limitation after 4 years. DESIGN: Cohort study. SETTING:
      Hong Kong, China. PARTICIPANTS: Four thousand men and women aged 65 and older
      living in the community who were ambulatory enough to attend the study center.
      METHODS: Interviewers obtained information regarding physical, psychological, and
      functional health; body mass index (BMI), grip strength, blood pressure, and
      ankle brachial index were determined. Three clinical frailty scales based on the
      Fried phenotype (Cardiovascular Health Study (CHS); Fatigue, Resistance,
      Ambulation, Illness, and Loss (FRAIL); and Hubbard) and a frailty index (FI) were
      constructed from these variables, and their ability to predict incident mortality
      and physical function limitations was compared using receiver operating
      characteristic (ROC) curves. RESULTS: All tools predicted adverse outcomes. More
      participants were categorized into frail and prefrail categories using the CHS
      than with the other two clinical scales. For all frailty measures, with
      increasing levels of frailty, the sensitivity fell and the specificity increased
      to greater than 90%; the area under the ROC curve values were approximately 0.6.
      CONCLUSION: Simple frailty scores are comparable with a multidimensional deficit
      accumulation FI in predicting mortality and physical limitations. The newer
      FRAIL, proposed for use in a clinical setting, is comparable with other existing
      short screening tools, as well as tools based on the multiple-deficits model used
      for research settings. Addition of a physical performance measure to screening
      tools may increase predictive accuracy.

PMID- 22861119
TI  - Fluorinated copolymer PCPDTBT with enhanced open-circuit voltage and reduced
      recombination for highly efficient polymer solar cells.
AB  - A novel fluorinated copolymer (F-PCPDTBT) is introduced and shown to exhibit
      significantly higher power conversion efficiency in bulk heterojunction solar
      cells with PC(70)BM compared to the well-known low-band-gap polymer PCPDTBT.
      Fluorination lowers the polymer HOMO level, resulting in high open-circuit
      voltages well exceeding 0.7 V. Optical spectroscopy and morphological studies
      with energy-resolved transmission electron microscopy reveal that the fluorinated
      polymer aggregates more strongly in pristine and blended layers, with a smaller
      amount of additives needed to achieve optimum device performance. Time-delayed
      collection field and charge extraction by linearly increasing voltage are used to
      gain insight into the effect of fluorination on the field dependence of free
      charge-carrier generation and recombination. F-PCPDTBT is shown to exhibit a
      significantly weaker field dependence of free charge-carrier generation combined
      with an overall larger amount of free charges, meaning that geminate
      recombination is greatly reduced. Additionally, a 3-fold reduction in non
      geminate recombination is measured compared to optimized PCPDTBT blends. As a
      consequence of reduced non-geminate recombination, the performance of optimized
      blends of fluorinated PCPDTBT with PC(70)BM is largely determined by the field
      dependence of free-carrier generation, and this field dependence is considerably
      weaker compared to that of blends comprising the non-fluorinated polymer. For
      these optimized blends, a short-circuit current of 14 mA/cm(2), an open-circuit
      voltage of 0.74 V, and a fill factor of 58% are achieved, giving a highest energy
      conversion efficiency of 6.16%. The superior device performance and the low band
      gap render this new polymer highly promising for the construction of efficient
      polymer-based tandem solar cells.

PMID- 22861120
TI  - Bosentan in heart transplantation candidates with severe pulmonary hypertension:
      efficacy, safety and outcome after transplantation.
AB  - BACKGROUND: Increased pulmonary vascular resistance (PVR) is associated with
      increased right ventricular failure and mortality after heart transplantation.
      METHODS: In this prospective study, 22 patients considered high-risk candidates
      for heart transplantation because of severe pulmonary hypertension (PVR = 6 +/- 2
      Wood units; transpulmonary gradient 22 +/- 7 mmHg), received bosentan 125 mg bid.
      Right heart catheterization was repeated after four months (n = 22) and 12 months
      (n = 9). Eleven patients who declined participation in the study were considered
      as control group. RESULTS: After four months, PVR decreased by 38% in patients
      receiving bosentan (n = 22), while it increased by 25% in the control group (p =
      0.001). Those patients who received bosentan for 12 months (n = 9), experienced a
      60% reduction in PVR compared to baseline (p = 0.003). Only three patients (14%)
      had no hemodynamic improvement with bosentan. After bosentan therapy, 14 patients
      (64%) underwent heart transplantation. Patients with high PVR who received
      bosentan showed a trend toward better one-yr survival after transplantation than
      patients with PVR <= 2.5 Wood units transplanted in the same period of time (93%
      vs. 83%). CONCLUSIONS: In patients considered high-risk candidates for heart
      transplantation because of high PVR, therapy with bosentan is associated with a
      significant reduction in PVR and a good outcome after transplantation.

PMID- 22861121
TI  - Pinhole carbon dioxide laser treatment of secondary anetoderma associated with
      juvenile xanthogranuloma.

PMID- 22861122
TI  - RNA interference: a promising technique for the improvement of traditional crops.
AB  - RNA interference (RNAi) is a homology-dependent gene-silencing technology that
      involves double-stranded RNA directed against a target gene. This technique has
      emerged as powerful tool in understanding the functions of a number of genes in
      recent years. For the improvement in the nutritional status of the plants and
      reduction in the level of antinutrients, the conventional breeding methods were
      not completely successful in achieving the tissue-specific regulation of some
      genes. RNAi has shown successful results in a number of plant species for
      nutritional improvement, change in morphology and alteration in metabolite
      synthesis. This technology has been applied mostly in genetic engineering of
      important crop plants, and till date there are no reports of its application for
      the improvement of traditional/underutilized crops. In this study, we discuss
      current knowledge of RNAi function and concept and strategies for the improvement
      of traditional crops. Practical application. Although RNAi has been extensively
      used for the improvement of popular crops, no attention has been given for the
      use of this technology for the improvement of underutilized crops. This study
      describes the importance of use of this technology for the improvement of
      underutilized crops.

PMID- 22861123
TI  - Monolithic precolumns as efficient tools for guiding the design of
      nanoparticulate drug-delivery formulations.
AB  - The development of nanomedicines for improved diagnosis and treatment of diseases
      is pushing current analytical methods to their limits. More efficient,
      quantitative high-throughput screening methods are needed to guide the
      optimization of promising nanoparticulate drug delivery formulations. In response
      to this need, we present herein a novel approach using monolithic separation
      media. The unique porosity of our capillary monolithic precolumns allows the
      direct injection and online removal of protamine-oligonucleotide nanoparticles
      ("proticles") without column clogging, thus avoiding the need for time-consuming
      off-line sample workup. Furthermore, ring-opening metathesis polymerization
      (ROMP)-derived monoliths show equivalent preconcentration efficiency for the
      target drug vasoactive intestinal peptide (VIP) as conventional particle-packed
      precolumns. The performance of the ROMP-derived monolithic precolumns was
      constant over at least 100 injections of crude proticle-containing and 300
      injections of highly acidic samples. Applying a validated LC-MS/MS capillary
      monolithic column switching method, we demonstrate the rapid determination of
      both drug load and in vitro drug release kinetics of proticles within the
      critical first 2 h and investigate the stability of VIP-loaded proticles in
      aqueous storage medium intended for inhalation therapy.

PMID- 22861124
TI  - A novel missense mutation in the gene FZD6 underlies autosomal recessive nail
      dysplasia.
AB  - BACKGROUND: Inherited isolated nail anomaly manifesting with onychauxis and
      onycholysis is a rare condition, caused by mutations in the gene FZD6, encoding
      membrane-bound Wnt receptor protein. OBJECTIVES: To search for sequence variants
      in the gene FZD6 in three individuals of a consanguineous family exhibiting
      features of nail dysplasia. METHODS: Linkage in the family was searched by
      genotyping microsatellite markers linked to the gene FZD6, mapped at chromosome
      8q22.3. Exons and splice junction sites of the gene FZD6 were polymerase chain
      reaction amplified and sequenced in an automated DNA sequencer. RESULTS: DNA
      sequence analysis revealed a novel homozygous missense mutation (c.1266G>A;
      p.Gly422Asp) located in the transmembrane domain of the protein FZD6.
      CONCLUSIONS: The missense mutation (p.Gly422Asp), identified here, is only the
      third mutation detected in the gene FZD6.

PMID- 22861125
TI  - Assessment of nutritional status and meal-related situations among patients with
      chronic obstructive pulmonary disease in Primary health care - obese patients; a
      challenge for the future.
AB  - AIMS AND OBJECTIVES: To describe nutritional status, meal related situations,
      food habits and food preferences of patients with chronic obstructive pulmonary
      disease (COPD) in a Primary health care (PHC) setting. BACKGROUND: To date,
      guidelines have mainly focused on underweight patients with COPD, as a low body
      mass index (BMI) is a risk factor for mortality. However, in recent years there
      has been an increase in the number of overweight patients with COPD, and
      therefore nutritional management must be developed to cover problems related to
      both under and overweight. DESIGN: Descriptive. METHODS: One hundred and three
      patients from PHC centres representing COPD stages 2 and 3 were included. The
      Mini Nutritional Assessment (MNA) was used to collect nutritional status data
      while semi-structured interviews provided information on food and meal related
      situations. RESULTS: Mean age was 69 (+/- 5)years and 45% were women. Among all
      patients mean BMI was 27 and 14% had a BMI <= 21 kg/m(2) . More women (31%) than
      men (26%) had a BMI >= 30 kg/m(2) . According to the MNA screening score, 86% of
      the patients were assessed as normal or not at risk of malnutrition. The total
      MNA assessment score revealed that 10 patients were at risk of malnutrition or
      malnourishment. Problems with meal related situations were mostly associated with
      eating, and only a small number reported difficulties with shopping or preparing
      food. CONCLUSIONS: In PHC, more patients with COPD were obese than malnourished
      and their self-reported nutritional status was not always accurate. RELEVANCE TO
      CLINICAL PRACTICE: It is challenging to identify the patient's nutritional
      status, individualize nutritional care and educate obese patients with COPD at
      PHC centres. It is necessary to develop screening instruments to assess the risk
      of both obesity and malnutrition.

PMID- 22861126
TI  - Monte Carlo simulation for the double layer structure of an ionic liquid using a
      dimer model: a comparison with the density functional theory.
AB  - Theoretical difficulties in describing the structure and thermodynamics of an
      ionic liquid double layer are often associated with the nonspherical shapes of
      ionic particles and extremely strong electrostatic interactions. The recent
      density functional theory predictions for the electrochemical properties of the
      double layer formed by a model ionic liquid wherein each cation is represented by
      two touching hard spheres, one positively charged and the other neutral, and each
      anion by a negatively charged hard spherical particle, remain untested in this
      strong coupling regime. We report results from a Monte Carlo simulation of this
      system. Because for an ionic liquid the Bjerrum length is exceedingly large, it
      is difficult to perform simulations under conditions of strong electrostatic
      coupling used in the previous density functional theory study. Results are
      obtained for a somewhat smaller (but still large) Bjerrum length so that reliable
      simulation data can be generated for a useful test of the corresponding
      theoretical predictions. On the whole, the density profiles predicted by the
      theory are quite good in comparison with the simulation data. The strong
      oscillations of ionic density profiles and the local electrostatic potential
      predicted by this theory are confirmed by simulation, although for a small
      electrode charge and strong electrostatic coupling, the theory predicts the
      contact ionic densities to be noticeably different from the Monte Carlo results.
      The theoretical results for the more important electrostatic potential profile at
      contact are given with good accuracy. 

PMID- 22861127
TI  - Adult worm-specific IgE/IgG4 balance is associated with low infection levels of
      Schistosoma mansoni in an endemic area.
AB  - Field studies have suggested an immune-mediated mechanism associated with
      resistance to Schistosoma mansoni infection. Overall, levels of specific IgE have
      been correlated with resistance to infection, whereas levels of IgG4 have been
      associated with susceptibility. This study aimed to evaluate serum levels of
      soluble adult worm antigen preparation (SWAP)-specific IgE and IgG4 in relation
      to current infection in a large casuistic of individuals living in an endemic
      area of schistosomiasis in Bahia, Brazil. The prevalence of S. mansoni infection
      was 37.7% and the mean parasite burden was 55.4 (0-2100) epg/faeces. There was no
      significant difference in the levels of SWAP-specific IgE in individuals with
      different parasite burden, whereas high producers of parasite-specific IgG4
      presented higher parasite burden when compared to low IgG4 producers.
      Additionally, S. mansoni parasite load was positively correlated with the levels
      of specific IgG4 or total IgE. No significant correlation was observed between
      parasite burden and SWAP-specific IgE. Nevertheless, SWAP-specific IgE/IgG4 ratio
      was higher in uninfected or lightly infected individuals (1-99 epg/faeces) than
      in heavily infected ones (>=400 epg/feces). These findings highlight the
      important role of IgE/IgG4 ratio in the resistance to infection, which could be
      useful for further studies in schistosomiasis vaccine candidates.

PMID- 22861128
TI  - Anxiety-linked expectancy bias across the adult lifespan.
AB  - Anxiety is characterised by a negative expectancy bias, such that anxious
      individuals report negatively distorted expectations about the future. Contrary
      to anxiety, ageing is characterised by a positivity effect, such that ageing is
      associated with a tendency to attend to and remember positive information,
      relative to negative information. The current study integrates these literatures
      to examine anxiety- and age-linked biases when thinking about the future.
      Participants (N=1,109) completed a procedure that involved reading valenced
      scenarios (positive, negative, or ambiguous) and then rating the likelihood of
      future valenced events occurring. Results suggest that ageing and anxiety have
      independent and opposing effects. Heightened anxiety was associated with a
      reduced expectancy for positive events, regardless of the scenarios' current
      emotional valence, whereas increased age was associated with an inflated
      expectancy for positive events, which was strongest when individuals were
      processing socially relevant or negative scenarios.

PMID- 22861129
TI  - Food for thought: attenuation of dopamine signaling by insulin (commentary on
      Mebel et al.).

PMID- 22861131
TI  - Physiological measurements as validation of alertness observations: an
      exploratory case study of three individuals with profound intellectual and
      multiple disabilities.
AB  - Although observation largely takes into account the needs and abilities of
      individuals with profound intellectual and multiple disabilities, several
      difficulties are related to this assessment method as well. Our aim in this study
      was to investigate what possibilities the use of physiological measurements make
      available to validate alertness observations. Measurements of five physiological
      parameters were compared with video observations of three individuals with
      profound intellectual and multiple disabilities. Because our first findings are
      broadly in line with those of studies involving individuals in the general
      population, we hypothesize that physiological measurements can be used to
      validate alertness observations in individuals with profound intellectual and
      multiple disabilities. Future studies are needed to compensate for the
      limitations of this study and to answer ensuing questions.

PMID- 22861130
TI  - Racial and ethnic disparities in quality of health care among children with
      autism and other developmental disabilities.
AB  - We examined racial and ethnic disparities in quality of care for children with
      autism and other developmental disabilities and whether disparities varied for
      children with autism compared to children with other developmental disabilities.
      Analyzing data from the National Survey of Children with Special Health Care
      Needs (N  =  4,414), we compared Black and Latino children to White children. We
      found racial and ethnic disparities on 5 of 6 quality outcomes. The interaction
      between race and disability status indicated that disparities in quality
      indicators were exacerbated among families of children with autism. These
      analyses suggest that children with autism, particularly those who are Latino and
      Black, face greater challenges in receiving high-quality health care.

PMID- 22861132
TI  - Seven interactional benefits of physical tasks for people with intellectual
      disability.
AB  - People with intellectual disability can be supported by staff encouraging their
      skills in communication and in physical tasks. In a qualitative study, I used
      video evidence from a residential home and from 2 garden therapy services to
      argue that physical tasks are structurally more likely to result in successful
      performance (and corresponding positive assessment), whereas verbal tasks tend to
      result in failure (and corresponding correction and unsatisfactory interaction).
      I suggested 7 distinguishing characteristics of the 2 kinds of task and briefly
      discussed the policy implications for supporting people with intellectual
      disability.

PMID- 22861133
TI  - Shared decision making: improving care for children with autism.
AB  - We assessed the extent to which parents of children with autism spectrum disorder
      report that they are engaged in shared decision making. We measured the
      association between shared decision making and (a) satisfaction with care, (b)
      perceived guidance regarding controversial issues in autism spectrum disorder,
      and (c) perceived assistance navigating the multitude of treatment options.
      Surveys assessing primary medical care and decision-making processes were
      developed on the basis of the U.S. Department of Health and Human Service's
      Consumer Assessment of Healthcare Providers and Systems survey. In May 2009,
      after pilot testing, we sent surveys to 203 parents of children from ages 3 to 18
      with International Classification of Diseases-9 and parent-confirmed autism
      spectrum disorder diagnoses. The response rate was 64%. Controlling for key
      demographic variables, parents of children with autism spectrum disorder
      reporting higher levels of shared decision making reported significantly greater
      satisfaction with the overall quality of their child's health care (p <= .0001).
      Parents reporting higher levels of shared decision making were also significantly
      more likely to report receiving guidance on the many treatment options (p  = 
      .0002) and controversial issues related to autism spectrum disorder (p  = 
      .0322). In this study, shared decision making was associated with higher parent
      satisfaction and improved guidance regarding treatments and controversial issues
      within primary care for children with autism spectrum disorder.

PMID- 22861134
TI  - A longitudinal study of narrative development in children and adolescents with
      Down syndrome.
AB  - The present study examined narrative development in children and adolescents with
      Down syndrome longitudinally. Narratives were collected from 32 children and
      adolescents with Down syndrome three times over a 1-year period. Both micro- and
      macrolevel analyses were conducted. Significant growth over the 1-year period was
      seen in semantic complexity and narrative structure. However, there was no
      evidence of growth in syntactic complexity or narrative length. Mental age and
      comprehension skills at Time 1 predicted scores in all 4 areas at Time 3.
      Expressive language skills added further to the prediction of syntactic
      complexity and story length.

PMID- 22861135
TI  - Measuring physical activity with pedometers in older adults with intellectual
      disability: reactivity and number of days.
AB  - The minimum number of days of pedometer monitoring needed to estimate valid
      average weekly step counts and reactivity was investigated for older adults with
      intellectual disability. Participants (N  =  268) with borderline to severe
      intellectual disability ages 50 years and older were instructed to wear a
      pedometer for 14 days. The outcome measure was steps per day. Reactivity was
      investigated with repeated measures analysis of variance, and monitoring frame
      was assessed by comparing combinations of days with average weekly step counts
      (with intraclass correlation coefficients [ICCs] and regression analyses). No
      reactivity was present. Any combination of 4 days resulted in ICCs of 0.96 or
      higher and 90% of explained variance. The study concludes that any 4 days of
      wearing a pedometer is sufficient to validly measure physical activity in older
      adults with intellectual disability.

PMID- 22861136
TI  - Self-reported health of people with intellectual disability.
AB  - Self-reported health is an important outcome in the evaluation of health care but
      is largely ignored in favor of proxy-based reporting for people with an
      intellectual disability. This study briefly reviews the role of self-report in
      health assessment of people with intellectual disability and the challenges and
      recommendations that have emerged from the considerable body of research on
      interviewing and self-report. Limitations in current recommendations are
      addressed from the perspective of the cognition of self-report. The review
      describes conceptual directions for the reconciliation of the two contradictory
      themes in the treatment of self-report: the centrality given to personal
      perceptions and choices and the methodological concerns over the meaningfulness
      and validity of the self-reporting process.

PMID- 22861138
TI  - Comparative characteristics of the home care nursing services used by community
      dwelling older people from urban and rural environments.
AB  - AIM: To compare home care nursing services use by community-dwelling older people
      from urban and rural environments in Poland. BACKGROUND: In the current
      literature, there is a lack of data based on multidimensional geriatric
      assessment concerning the provision of care delivered by nurses for older people
      from urban and rural environments. DESIGN: Cross-sectional random survey. METHOD:
      Between 2006-2010, a random sample of 935 older people (over 65 years of age)
      from an urban environment and 812 from a neighbouring rural environment were
      interviewed in a cross-sectional survey. FINDINGS: The rural dwellers (82.8%)
      nominated their family members as care providers more often than the city
      inhabitants (51.2%). Home nursing care was provided to 4.1% of people in the city
      and 6.5% in the county. Poststroke condition, poor nutritional status, and low
      physical activity level, as well as low scores for activities of daily living,
      instrumental activities of daily living, and Mini-Mental State Examination
      values, were all determinants of nursing care, both in urban and rural areas. In
      the urban environment, additional predictors of nursing care use were age,
      presence of ischaemic heart disease, diabetes and respiratory disorders, number
      of medications taken, and a high depression score. CONCLUSIONS: Poor functional
      status is the most important determinant of nursing care use in both
      environments. In the urban environment, a considerable proportion of community
      dwelling elders live alone. In the rural environment, older people usually have
      someone available for potential care services. The main problem seems to be
      seeking nursing care only in advanced deterioration of functional status.

PMID- 22861139
TI  - Two independent activities define Ccm1p as a moonlighting protein in
      Saccharomyces cerevisiae.
AB  - Ccm1p is a nuclear-encoded PPR (pentatricopeptide repeat) protein that localizes
      into mitochondria of Saccharomyces cerevisiae. It was first defined as an
      essential factor to remove the bI4 [COB (cytochrome b) fourth intron)] and aI4
      [COX1 (cytochrome c oxidase subunit 1) fourth intron] of pre-mRNAs, along with
      bI4 maturase, a protein encoded by part of bI4 and preceding exons that removes
      the intronic RNA sequence that codes for it. Later on, Ccm1p was described as key
      to maintain the steady-state levels of the mitoribosome small subunit RNA (15S
      rRNA). bI4 maturase is produced inside the mitochondria and therefore its
      activity depends on the functionality of mitochondrial translation. This report
      addresses the dilemma of whether Ccm1p supports bI4 maturase activity by keeping
      steady-state levels of 15S rRNA or separately and directly supports bI4 maturase
      activity per se. Experiments involving loss of Ccm1p, SMDC (sudden mitochondrial
      deprivation of Ccm1p) and mutations in one of the PPR (pentatricopeptide repeat)
      motifs revealed that the failure of bI4 maturase activity in CCM1 deletion
      mutants was not due to a malfunction of the translational machinery. Both
      functions were found to be independent, defining Ccm1p as a moonlighting protein.
      bI4 maturase activity was significantly more dependent on Ccm1p levels than the
      maintenance of 15S rRNA. The novel strategy of SMDC described here allowed the
      study of immediate short-term effects, before the mutant phenotype was
      definitively established. This approach can be also applied for further studies
      on 15S rRNA stability and mitoribosome assembly.

PMID- 22861140
TI  - In vitro antioxidant capacity and antigenotoxic properties of protoporphyrin and
      structurally related tetrapyrroles.
AB  - The antioxidant properties of protoporphyrin IX and related tetrapyrroles are
      poorly characterized. Therefore, eight tetrapyrroles, five of which are produced
      in vivo, were tested to assess their antioxidant capacities in the Salmonella
      reverse mutation, TEAC, FRAP and ORAC assays. Tertiary-butyl hydroperoxide (tert
      BOOH) in the presence or absence of metabolic activation (+/-S9) was added to
      Salmonella strain TA102 together with the test compounds. In the absence of
      metabolic activation, the order of effectiveness was protoporphyrin > biliverdin
      > bilirubin ditaurate > bilirubin > biliverdin dimethyl ester > stercobilin >
      bilirubin dimethyl ester > urobilin. In the presence of S9, the effectiveness was
      reversed, with urobilin > biliverdin dimethyl ester > bilirubin dimethyl ester >
      stercobilin > biliverdin > bilirubin > bilirubin ditaurate > protoporphyrin. In
      the antioxidant capacity assays FRAP, TEAC and ORAC, mainly bilirubin, bilirubin
      ditaurate, biliverdin and protoporphyrin showed antioxidant activity. This study
      reports that previously untested tetrapyrroles of related structure prevent
      oxidatively induced genotoxicity, and for some, novel underlying mechanisms of
      antioxidant action were revealed. These results support the physiological
      importance and biological relevance of tetrapyrroles including protoporphyrin
      that might act as antioxidants, protecting from oxidatively induced DNA damage,
      particularly in the tissues/organs where they accumulate.

PMID- 22861141
TI  - A non-heme iron(III) complex with porphyrin-like properties that catalyzes
      asymmetric epoxidation.
AB  - In this report, we describe an iron(III) complex containing a carbazole-based
      tridentate ligand that catalyzes highly enantioselective asymmetric epoxidation
      of (E)-alkenes at room temperature. The non-heme iron(III) complex has a five
      coordinated trigonal-bipyramidal structure, and its two-electron oxidized state
      has the similar electronic structure as that of iron porphyrins.

PMID- 22861142
TI  - Pedicle ligation in ovariohysterectomy: an in vitro study of ligation techniques.
AB  - OBJECTIVES: Ligature failure is an important complication following
      ovariohysterectomy in the bitch. The aim of this study was to assess the
      differences between five individual ligation techniques in their ability to
      attenuate a bulky vascular model. METHODS: A vascular model was constructed that
      enabled the occlusive ability of five different ligation techniques to be
      measured including the square knot, surgeon's knot, slip knot, modified
      transfixing ligature and the single-double other side knot. Each was constructed
      using both USP-0 polyglyconate and polyglactin 910 suture material. The extent of
      attenuation of the vascular model that was achieved by each technique was
      assessed using pressure transducers. RESULTS: In this model, the slip knot,
      modified transfixing ligature and the single-double other side knot outperformed
      the square and surgeon's knots. CLINICAL SIGNIFICANCE: The results of this study
      suggest that utilising a knot design that has more inherent resistance to
      slippage of the first throw (e.g. the modified transfixing ligature, slip or
      single-double other side knots) may be preferable over square and surgeon's knots
      when tying a ligature on a bulky vascular pedicle like the ovarian stump in a
      large bitch.

PMID- 22861143
TI  - One-pot, three-component coupling approach to the synthesis of alpha
      iminocarboxamides.
AB  - A one-pot, three-component coupling was accomplished via the nucleophilic
      addition of an alkylsamarium(III) species to isocyanides and the subsequent
      addition of the resultant imidoyl samarium(III) species to isocyanates under mild
      conditions for the formation of alpha-iminocarboxamides. The developed sequential
      C-C bond-forming procedure enabled the rapid synthesis of the alpha
      iminocarboxamides in good to excellent yields from readily available starting
      materials.

PMID- 22861145
TI  - Psoriasis in children: should we be worried about comorbidities?

PMID- 22861144
TI  - Does reduction in mycophenolic acid dose compromise efficacy regardless of
      tacrolimus exposure level? An analysis of prospective data from the Mycophenolic
      Renal Transplant (MORE) Registry.
AB  - Prospective data are lacking concerning the effect of reduced mycophenolic acid
      (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure.
      The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational
      study of de novo kidney transplant patients receiving MPA therapy under routine
      management. The effect of MPA dose reduction, interruption, or discontinuation
      (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%)
      reduced tacrolimus (<= 7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus
      (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate
      mofetil 281 (32.3%). During baseline to month 1, months 1-3, months 3-6, and
      months 6-12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535)
      patients, respectively, required MPA dose changes. These patients experienced an
      increased risk of biopsy-proven acute rejection at one yr with tacrolimus
      exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28-5.29,
      p = 0.008) or excluded (HR 2.58, 95% CI 1.28-5.23, p = 0.008). MPA dose changes
      were significantly associated with one yr graft failure when tacrolimus exposure
      was included (HR 2.23; 95% CI 1.01-4.89, p = 0.047) but not when tacrolimus
      exposure was excluded (HR 2.16; 95% CI 0.99-4.79; p = 0.054). These results
      suggest that reducing or discontinuing MPA can adversely affect graft outcomes
      regardless of tacrolimus trough levels.

PMID- 22861146
TI  - Pyogenic liver abscess and colorectal neoplasia: a case series.
AB  - BACKGROUND: Colorectal neoplasia is occasionally associated with hepatic abscess.
      To identify cases, we retrospectively analyzed the medical records of all
      patients admitted to our hospital for liver abscess from 2004 to 2008. METHODS:
      Underlying disease was actively sought for all patients. Cases with obvious
      causes, such as biliary tract obstruction and immunocompromising conditions, were
      excluded. RESULTS: Out of 211 cases of liver abscess included, 12 were found to
      be associated with colorectal neoplasia. None of these 12 cases had
      gastrointestinal symptoms. The stool occult blood test was positive in only 3
      cases. There were 3 cases of focal adenocarcinoma in tubulovillous adenoma and
      the remaining 9 cases all had adenomatous polyps. Complete cure was achieved in
      all cases. CONCLUSIONS: When managing patients with liver abscess, colorectal
      neoplasia should be considered as a possible associated underlying condition.

PMID- 22861147
TI  - Treatment of argyria using the quality-switched 1,064-nm neodymium-doped yttrium
      aluminum garnet laser: efficacy and persistence of results at 1-year follow-up.

PMID- 22861148
TI  - Escape from metaignorance: how children develop an understanding of their own
      lack of knowledge.
AB  - Previous research yielded conflicting results about when children can accurately
      assess their epistemic states in different hiding tasks. In Experiment 1, ninety
      two 3- to 7-year-olds were either shown which object was hidden inside a box,
      were totally ignorant about what it could be, or were presented with two objects
      one of which was being put inside (partial exposure). Even 3-year-olds could
      assess their epistemic states in the total ignorance and the complete knowledge
      task. However, only children older than 5 could assess their ignorance in the
      partial exposure task. In Experiment 2 with one hundred and one 3- to 7-year
      olds, similar results were found for children under 5 years even when more
      objects were shown in partial exposure tasks. Implications for children's
      developing theory of knowledge are discussed.

PMID- 22861149
TI  - A qualitative approach to examine women's experience of planned cesarean.
AB  - OBJECTIVE: To investigate women's expectations regarding cesarean and to assess
      the subjective experience of birth of these women. Because the birth experience
      is a multidimensional phenomenon, qualitative as well as quantitative approaches
      were used to investigate women's expectations and experiences with cesarean.
      DESIGN: Descriptive cohort study. SETTING: The Division of Obstetrics and Feto
      Maternal Medicine of the Department of Obstetrics and Gynecology of an Austrian
      medical university. PARTICIPANTS: Forty-eight women with a planned cesarean
      birth. METHODS: Semistructured interviews were conducted with the 48 women before
      (36(th)  week of gestation) the planned cesarean and shortly thereafter. Data
      were analyzed by means of a qualitative content analysis. Anxiety, depression,
      and psychological distress were assessed using standardized questionnaires.
      RESULTS: More than three fourths (81.3%) of the women were satisfied with the
      cesarean. Nevertheless, 83.3% of the women expressed anxiety about cesarean,
      including fears about the health of the infant, the epidural anesthesia, and
      possible complications. Before the cesarean, only one half of the women (54.2%)
      felt that they had been sufficiently informed about the planned cesarean, and
      only 25% had detailed knowledge about the specific course of events of the
      cesarean. Quantitative assessment showed low depression levels and overall
      psychological distress before and after the cesarean. State anxiety levels were
      high before the cesarean and moderate afterwards. CONCLUSION: Although the
      overall satisfaction and psychological tolerability of a planned cesarean is
      high, improvement is possible by providing more detailed information to the
      prospective mothers and by specifically addressing prevalent anxieties.

PMID- 22861150
TI  - Effects of ortho substituent groups of protocatechualdehyde derivatives on
      binding to the C1 domain of novel protein kinase C.
AB  - Diacylglycerol (DAG) regulates a broad range of cellular functions including
      tumor promotion, apoptosis, differentiation, and growth. Thus, the DAG-responsive
      C1 domain of protein kinase C (PKC) isoenzymes is considered to be an attractive
      drug target for the treatment of cancer and other diseases. To develop effective
      PKC regulators, we conveniently synthesized (hydroxymethyl)phenyl ester analogues
      targeted to the DAG binding site within the C1 domain. Biophysical studies and
      molecular docking analysis showed that the hydroxymethyl group, hydrophobic side
      chains, and acyl group at the ortho position are essential for their interactions
      with the C1-domain backbone. Modifications of these groups showed diminished
      binding to the C1 domain. The active (hydroxymethyl)phenyl ester analogues showed
      more than 5-fold stronger binding affinity for the C1 domain than DAG. Therefore,
      our findings reveal that (hydroxymethyl)phenyl ester analogues represent an
      attractive group of C1-domain ligands that can be further structurally modified
      to improve their binding and activity.

PMID- 22861151
TI  - A clinical action measure to assess glycemic management in the 65-74 year old
      veteran population.
AB  - OBJECTIVES: To evaluate the effect of including of clinical actions within 6
      months of a glycosylated hemoglobin (HbA1c) level greater than 8% upon measure
      adherence (pass rates) and to assess the association between patient factors and
      the likelihood of not passing. SETTING: Veterans Health Administration. DESIGN:
      Retrospective cohort study for FY2002 to FY2004. PARTICIPANTS: One hundred fifty
      three thousand one hundred thirty-two veterans aged 65-74 with diabetes mellitus
      not taking insulin; 99% were male and 86% white. MEASUREMENTS: The clinical
      action measure included three categories: (a) initial pass (index HbA1c < 8%);
      (b) modified pass (index HbA1c >= 8%), and the hierarchical occurrence of one of
      the following events within 6 months after date of index HbA1c: subsequent HbA1c
      < 8%, being started on insulin (100% weight), new oral medication (50% weight),
      care in a diabetes mellitus-related clinic (25% weight); and (c) failure (no
      category met or HbA1c > 9%). Multinomial logistic regression models were used to
      evaluate associations between participant factors and the likelihood of not
      passing initially. RESULTS: Most (82.6%) or the participants had an index HbA1c
      of less than 8%, and 10.6% were in the modified pass group. The failure rate
      (17.4%) fell to 6.8% when actions were weighted equally and to 9.4% using
      different weights. Veterans who are African American (odds ratios (ORs) = 1.43
      and 1.44), unmarried (ORs = 1.19 and 1.24), poor (ORs = 1.36 and 1.17), or taking
      two or more oral antihyperglycemic agents (ORs = 2.61 and 3.72) were
      significantly more likely to be in the modified pass and failure groups,
      respectively. CONCLUSION: Most veterans with an initial HbA1c of 8% or greater
      had clinical actions within 6 months. A measure that incorporates multiple
      treatment options, including education and nutrition, could be of benefit by
      encouraging dialogue of such options between patients and clinicians.

PMID- 22861152
TI  - Magnetic in-tube solid phase microextraction.
AB  - We report a new in-tube solid phase microextraction approach named magnetic in
      tube solid phase microextraction, magnetic-IT-SPME. Magnetic-IT-SPME has been
      developed, taking advantage of magnetic microfluidic principles with the aim to
      improve extraction efficiency of IT-SPME systems. First, a magnetic hybrid
      material formed by Fe(3)O(4) nanoparticles supported on SiO(2) was synthesized
      and immobilized in the surface of a bared fused silica capillary column to obtain
      a magnetic adsorbent extraction phase. The capillary column was placed inside a
      magnetic coil that allowed the application of a variable magnetic field.
      Acetylsalicylic acid, acetaminophen, atenolol, diclofenac, and ibuprofen were
      tested as target analytes. The application of a controlled magnetic field
      resulted in quantitative extraction efficiencies of the target analytes between
      70 and 100%. These results demonstrated that magnetic forces solve the low
      extraction efficiency (10-30%) of IT-SPME systems, which is one of their main
      drawbacks.

PMID- 22861153
TI  - Topical drug delivery systems in dermatology: a review of patient adherence
      issues.
AB  - INTRODUCTION: Until now, the main focus of medication adherence research has been
      oral drugs. Fewer studies have examined adherence to topical drugs. The issue of
      patient adherence to topical drugs is particularly significant in relation to
      chronic skin diseases, including psoriasis, atopic dermatitis, and acne, which
      require long-term use of topical medications. AREAS COVERED: The authors reviewed
      the current evidence of adherence to topical therapy in dermatological diseases,
      mainly focusing on psoriasis, atopic dermatitis, and acne. The predictors or
      factors influencing adherence to topical therapy are then discussed. In general,
      the prevalence of poor adherence to topical drugs is high in dermatology.
      However, this research area remains empirically underdeveloped. We are still
      facing challenges in measuring topical medication adherence. EXPERT OPINION: The
      authors recommend some possible ways to improve topical medication adherence and
      provide some future research directions. Taking patient preference into
      consideration in selecting the right topical delivery vehicle is particularly
      important in improving patient adherence. Better drug design, formulation, or
      technology may be another important direction. Other possible effective ways to
      improve topical medication adherence include good physician-patient relationship,
      patient education, individualized treatment plan, psychological intervention,
      electronic devices, and return visits.

PMID- 22861154
TI  - The experience of becoming a grandmother to a premature infant - a balancing act,
      influenced by ambivalent feelings.
AB  - AIMS AND OBJECTIVES: To explore and describe the experience of becoming a
      grandmother to a premature infant. BACKGROUND: Becoming a grandmother involves a
      new perspective of life. Grandmothers of sick infants find themselves in a new
      situation with an adult child undergoing serious stress. Few studies have
      approached the grandmothers' own experience of becoming a grandmother to a
      premature infant. DESIGN: A qualitative content analysis was used. METHODS:
      Eleven women, 52-66 years of age, who were grandmothers to premature infants born
      at a gestational age of 25-34 weeks, were interviewed during 2010. The infants
      were less than three years old at the time of the interview. The interviews were
      analysed with qualitative content analysis. RESULTS: The overall theme was a
      balancing act. Two categories of experience were identified: emotional
      experiences and a new role. 'Emotional experiences' was related to the first
      meeting, ambivalent feelings and confidence in care. 'A new role' was related to
      the subcategories supportive, a balance of involvement and limitations.
      CONCLUSIONS: To become a grandmother to a premature infant was experienced as a
      balancing act influenced by ambivalent feelings of joy, fear and worry. The
      grandmothers sensed the seriousness of the situation at the same time as they
      wanted to be happy about the newborn infant. They worried about their adult
      child's as well as the premature infant's health but put their own needs aside.
      The grandmothers' new role was a balance between being involved and supportive
      without disturbing. RELEVANCE TO CLINICAL PRACTICE: Neonatal intensive care unit
      staff should be open to grandmothers' needs and acknowledge them as an obvious
      support for the immediate family of a premature infant. The grandmothers need
      guidance and information about what to expect concerning the infants health, the
      parents situation and their own role.

PMID- 22861155
TI  - NMR studies of solid pentachlorophenol-4-methylpyridine complexes exhibiting
      strong OHN hydrogen bonds: geometric H/D isotope effects and hydrogen bond
      coupling cause isotopic polymorphism.
AB  - We have studied the hydrogen bond interactions of (15)N labeled 4-methylpyridine
      (4-MP) with pentachlorophenol (PCP) in the solid state and in polar solution
      using various NMR techniques. Previous spectroscopic, X-ray, and neutron
      crystallographic studies showed that the triclinic 1:1 complex (4-MPPCP) exhibits
      the strongest known intermolecular OHN hydrogen bond in the solid state. By
      contrast, deuteration of the hydrogen bond gives rise to the formation of a
      monoclinic structure exhibiting a weaker hydrogen bond. By performing NMR
      experiments at different deuterium fractions and taking advantage of dipolar (1)H
      (15)N recoupling under combined fast MAS and (1)H decoupling, we provide an
      explanation of the origin of the isotopic polymorphism of 4-MPPCP and improve
      previous chemical shift correlations for OHN hydrogen bonds. Because of
      anharmonic ground state vibrations, an ODN hydrogen bond in the triclinic form
      exhibits a shorter oxygen-hydron and a longer oxygen-nitrogen distance as
      compared to surrounding OHN hydrogen bonds, which also implies a reduction of the
      local dipole moment. The dipole-dipole interaction between adjacent coupled OHN
      hydrogen bonds which determines the structure of triclinic 4-MPPCP is then
      reduced by deuteration, and other interactions become dominant, leading to the
      monoclinic form. Finally, the observation of stronger OHN hydrogen bonds by (1)H
      NMR in polar solution as compared to the solid state is discussed.

PMID- 22861156
TI  - The end of growth? Analysing NHS nurse staffing.
AB  - AIM: To present an overview of UK National Health Service nurse staffing changes
      across the last 10 years. BACKGROUND: National Health Service funding is now
      being constrained as part of the overall measures to reduce UK public
      expenditure. This has implications for future staffing levels and deployment.
      Government and professional associations are disagreeing about the current extent
      of actual and likely National Health Service nurse staffing decline. DESIGN: The
      paper reviews 'official' data and evidence on National Health Service staffing to
      assess actual National Health Service nurse staffing trends in recent years,
      highlights the results of scenario modeling of future National Health Service
      nursing numbers and relates this to national policies on staffing. DISCUSSION:
      The available evidence now points to nurse staffing growth having tailed off and
      a likely pattern of overall decline in National Health Service nurse staffing is
      emerging. This is a policy concern in the UK, but also in many other countries.
      IMPLICATIONS FOR NURSING: Whilst there has been a 'recession benefit' to the UK
      nursing labour market, this supply side boost cannot continue indefinitely. Any
      continued trend towards reduced intakes to training and reduced staffing levels
      will intensify the debate about the appropriate staffing levels and skills mix.
      CONCLUSIONS: We have seen significant National Health Service nurse staffing
      growth in the last 10 years, which is likely now to reverse. The real measure of
      the effectiveness of local and national National Health Service nursing workforce
      policy is not how many nurses are employed, it is that sufficient are deployed to
      provide safe care.

PMID- 22861157
TI  - Endoscopically guided minimally invasive bypass tube intubation without DCR:
      evaluation of drainage and objective outcomes assessment.
AB  - AIM: To report a series of 15 consecutive patients with complete proximal
      bicanalicular obstructions managed with endoscopically guided minimally invasive
      placement of bypass tubes without a dacryocystorhinostomy (DCR), their
      indications, interventions, complications and objective and uniform assessment of
      outcomes. MATERIAL AND METHODS: Fifteen consecutive patients presenting with
      complete proximal bicanalicular obstructions were included in a retrospective,
      non-comparative case series. Medical records were reviewed for demographic data,
      etiology, symptoms at presentation, type of bypass tube used, length of the
      tubes, duration of follow-up, class of lacrimal drainage, patency of the tube,
      resolution of symptoms, complications and their outcomes. RESULTS: The mean age
      at presentation was 18.7 years (range: 10-32 years). The most common indication
      was punctal agenesis (46.6%) followed by complete proximal bicanalicular block
      secondary to trauma (26.6%). All patients presented with epiphora. The most
      common bypass tube was a straight Jones variety (60%). The mean length of the
      bypass tubes was 21 mm (range 19-24 mm). All patients were followed up for a mean
      duration of 9.6 months following surgery (range 7-13 months). The majority of the
      patients were post-operatively objectively classified into type I lacrimal
      drainage (66.6%). At the last follow-up, the success rate was 86.6%. None of the
      tubes extruded but were removed in two patients due to peritubal soft tissue
      infection and conjunctival pressure necrosis. CONCLUSION: Endoscopically guided
      minimally invasive placement of a bypass tube without DCR is an easier and
      effective alternative to the traditional conjunctivodacryocystorhinostomy and is
      likely to help in avoiding major complications of tube extrusion and malpositions
      seen with the latter procedure. Objective evaluation of lacrimal drainage helps
      in typifying and uniformly assessing the outcomes.

PMID- 22861158
TI  - Surgical treatment of ectopic pregnancy associated with predisposing factors of
      tuboperitoneal infertility.
AB  - OBJECTIVE: We sought to study the advantages of laparoscopic conservative
      treatment and pelvic reproductive surgery in patients with ectopic pregnancy and
      predisposing factors of tuboperitoneal infertility. MATERIAL AND METHODS:
      Patients who had undergone laparoscopic treatment for ectopic pregnancy were
      considered, with factors for tuboperitoneal infertility, while patients who
      underwent previous salpingectomy or assisted reproductive technology were
      excluded. The groups treated by salpingotomy (conservative) or salpingectomy
      (radical) were compared in terms of spontaneous intrauterine pregnancy rate,
      cumulative one-year pregnancy rate and recurrence of ectopic pregnancy. We
      considered patients treated with adhesiolysis, fimbrioplasty, and
      neosalpingostomy for tubal pathology as part of the fertility surgery group.
      RESULTS: Among 41 considered patients, 21 (51%) underwent conservative
      laparoscopic management of ectopic pregnancy. Twenty patients (49%) had
      salpingectomy. Despite the treatment of tuboperitoneal infertility factors in
      both groups, the pregnancy rate was significantly higher in the conservative
      group than in the radical one (76% vs 25%, p < 0.05). The overall cumulative rate
      of ectopic pregnancy recurrence was 22% and no significant difference was found
      between conservative and radical treatment (p 0.645). CONCLUSIONS: Salpingotomy
      should be preferred in all patients with ectopic pregnancy associated with
      factors of tuboperitoneal infertility. Infertility surgery clearly cannot help
      patients treated with salpingectomy, who obtain lower spontaneous pregnancy rates
      than those of the conservative group.

PMID- 22861159
TI  - Evaluation of preputial cytology in diagnosing oestrogen producing testicular
      tumours in dogs.
AB  - OBJECTIVES: The purpose of this study was to evaluate the diagnostic sensitivity
      and specificity of preputial cytology in oestrogen producing testicular tumours
      in dogs. METHODS: Forty-five dogs with palpable testicular masses and 30 healthy
      control dogs were included. Dogs were evaluated for signs of alopecia and/or
      feminisation. Analyses of preputial cytology, haematology and serum oestradiol
      were performed. Dogs with testicular masses were neutered and the testes were
      submitted for histopathological examination. The dogs were divided into three
      groups (1) control dogs (n=30), (2) dogs with a testicular mass and serum
      oestradiol concentration <40 pmol/L (n=35), (3) dogs with a testicular mass and
      serum oestradiol concentration >40 pmol/L (n=10). RESULTS: More than 20%
      superficial cells in preputial smear was significantly associated with serum
      oestradiol concentration >40 pmol/L (P<0.001). The number of superficial cells
      was significantly increased (P<0.001) in preputial smears from dogs with
      alopecia. CLINICAL SIGNIFICANCE: It appears that the preputial cytology has a
      high sensitivity and specificity for the diagnosis of oestrogen producing
      testicular tumours in dogs.

PMID- 22861160
TI  - Nitric oxide (*NO) generation but not ROS plays a major role in silibinin-induced
      autophagic and apoptotic death in human epidermoid carcinoma A431 cells.
AB  - Silibinin, a major active constituent of silymarin, is clinically used as a
      hepatoprotectant, and in recent years, it has been used for the treatment of
      cancer in China. Because the mechanism of silibinin action on cancer cells was
      still unclear, we investigated the contribution of silibinin to the induction of
      apoptosis and autophagy via generation of reactive oxygen species (ROS) and
      nitric oxide (*NO) in human epidermoid carcinoma A431 cells. Silibinin inhibited
      the cell growth in a dose-and time-dependent manner. Obvious autophagy was
      observed after treatment with different doses of silibinin. At a high dose (400
      MUM), silibinin induced apoptosis through both the intrinsic and extrinsic
      apoptotic pathways. Loss of mitochondrial membrane potential by silibinin led to
      mitochondrial dysfunction and decreased ROS levels, suggesting that silibinin
      might act as an antioxidant in this process. Furthermore, silibinin induced *NO
      generation in a time-and dose-dependent manner. The *NO scavenger PTIO could
      effectively clear *NO and exerted a minor cell protection effect through partial
      inhibition of silibinin-induced apoptosis and autophagy.

PMID- 22861161
TI  - Comparison of emergency medical services systems across Pan-Asian countries: a
      Web-based survey.
AB  - BACKGROUND: There are great variations in out-of-hospital cardiac arrest (OHCA)
      survival outcomes among different countries and different emergency medical
      services (EMS) systems. The impact of different systems and their contribution to
      enhanced survival are poorly understood. This paper compares the EMS systems of
      several Asian sites making up the Pan-Asian Resuscitation Outcomes Study (PAROS)
      network. Some preliminary cardiac arrest outcomes are also reported. METHODS:
      This is a cross-sectional descriptive survey study addressing population
      demographics, service levels, provider characteristics, system operations, budget
      and finance, medical direction (leadership), and oversight. RESULTS: Most of the
      systems are single-tiered. Fire-based EMS systems are predominant. Bangkok and
      Kuala Lumpur have hospital-based systems. Service level is relatively low, from
      basic to intermediate in most of the communities. Korea, Japan, Singapore, and
      Bangkok have intermediate emergency medical technician (EMT) service levels,
      while Taiwan and Dubai have paramedic service levels. Medical direction and
      oversight have not been systemically established, except in some communities.
      Systems are mostly dependent on public funding. We found variations in available
      resources in terms of ambulances and providers. The number of ambulances is 0.3
      to 3.2 per 100,000 population, and most ambulances are basic life support (BLS)
      vehicles. The number of human resources ranges from 4.0 per 100,000 population in
      Singapore to 55.7 per 100,000 population in Taipei. Average response times vary
      between 5.1 minutes (Tainan) and 22.5 minutes (Kuala Lumpur). CONCLUSION: We
      found substantial variation in 11 communities across the PAROS EMS systems. This
      study will provide the foundation for understanding subsequent studies arising
      from the PAROS effort.

PMID- 22861162
TI  - Pericellular matrix enhances retention and cellular uptake of nanoparticles.
AB  - A hydrated gel-like pericellular matrix (PCM) covers the surface of all
      eukaryotic cells and plays a key role in many cellular events, but its effect on
      nanoparticle internalization has not been studied. Here, using cells with various
      PCM thicknesses and gold nanoparticles as probes, we demonstrate that, rather
      than being a barrier to all foreign objects, the PCM can entrap and accumulate
      NPs, restrict and slow down their diffusion, and enhance their cellular uptake
      efficiency. Moreover, this newly discovered PCM function consumes energy and
      seems to be an integral part of the receptor-mediated endocytosis process. These
      findings are important in understanding the delivery mechanisms of nanocarriers
      for biomedical applications.

PMID- 22861163
TI  - Bendamustine compared with chlorambucil in previously untreated patients with
      chronic lymphocytic leukaemia: updated results of a randomized phase III trial.
AB  - The efficacy of bendamustine versus chlorambucil in a phase III trial of
      previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia
      (CLL) was re-evaluated after a median observation time of 54 months in May 2010.
      Overall survival (OS) was analysed for the first time. At follow-up, investigator
      assessed complete response (CR) rate (21.0% vs 10.8%), median progression-free
      survival (21.2 vs 8.8 months; P < 0.0001; hazard ratio 2.83) and time to next
      treatment (31.7 vs 10.1 months; P < 0.0001) were improved for bendamustine over
      chlorambucil. OS was not different between groups for all patients or those <=65
      years, >65 years, responders and non-responders. However, patients with objective
      response or a CR experienced a significantly longer OS than non-responders or
      those without a CR. Significantly more patients on chlorambucil progressed to
      second/further lines of treatment compared with those on bendamustine (78.3% vs
      63.6%; P = 0.004). The benefits of bendamustine over chlorambucil were achieved
      without reducing quality of life. In conclusion, bendamustine is significantly
      more effective than chlorambucil in previously untreated CLL patients, with the
      achievement of a CR or objective response appearing to prolong OS. Bendamustine
      should be considered as a preferred first-line option over chlorambucil for CLL
      patients ineligible for fludarabine, cyclophosphamide and rituximab.

PMID- 22861164
TI  - Factors associated with carriage of multi-resistant commensal Escherichia coli
      among postmenopausal women in Ujjain, India.
AB  - There is paucity of surveillance studies on antibiotic resistance in commensal
      Escherichia coli. The main aim of this cross-sectional study was to determine
      factors associated with peri-anal carriage of multi-resistant E. coli by healthy
      postmenopausal women. A structured questionnaire was completed for consecutive
      healthy postmenopausal women aged 45 y and above attending the outpatient clinics
      of the Department of Obstetrics and Gynaecology at R.D. Gardi Medical College,
      Ujjain, India. Antibiotic susceptibility testing was done by the Kirby-Bauer disk
      diffusion method, as recommended in the Clinical and Laboratory Standards
      Institute guidelines. The study showed that 28% of healthy women carried
      multidrug-resistant (MDR) E. coli in the peri-anal region. The factors
      significantly associated with carriage of MDR E. coli were family size > 10 (OR
      8.23, 95% CI 2.73-24.73; p < 0.001), antibiotic use in the past 2 weeks (OR 5.39,
      95% CI 2.36-12.34; p < 0.001), and hospitalization in the past 2 weeks (OR 4.02,
      95% CI 1.73-9.31; p = 0.001). This is the first study from India reporting the
      MDR E. coli carriage rate in healthy women aged over 45 y.

PMID- 22861166
TI  - Asymmetric time-dependent activation of right central amygdala neurones in rats
      with peripheral neuropathy and pregabalin modulation.
AB  - Neuropathic pain (NP) often presents with comorbidities, including depression and
      anxiety. The amygdala is involved in the processing of mood disorders, fear, and
      the emotional-affective components of pain. Hemispheric lateralization of pain
      processing in the amygdala has recently been brought to light because,
      independently of the side of the peripheral injury, the right central nucleus of
      the amygdala (CeA) showed higher neuronal activity than the left in models of
      inflammatory pain. Although the CeA has been called the 'nociceptive amygdala',
      because of its high content of nociceptive neurones, little is known about
      changes in its neuronal function in vivo, under NP conditions. Herein, we
      quantified CeA spontaneous and evoked activity in rats subjected to spinal nerve
      ligation (SNL), under isoflurane anaesthesia, following application of mechanical
      and thermal stimuli to widespread body areas. We found that spontaneous and
      stimulus-evoked neuronal activity was higher in the left CeA at 2 and 6 days
      after SNL induction and declined afterwards, whereas activity in the right CeA
      became dominant at 14 days after surgery, independently of the side of surgery.
      We also observed that systemic injection of pregabalin, which is widely used in
      patients with NP, reduced CeA spontaneous and stimulus-evoked neuronal activity.
      Overall, we observed that peripheral nerve injury produced asymmetric plasticity
      in ongoing and evoked activity in the left and right CeA. Remarkably, at 14 days
      after SNL induction, enhanced evoked activity in the right CeA persisted compared
      to short-term increases in activity in the left CeA. The plasticity found in
      ongoing and evoked activity was inhibited by pregabalin.

PMID- 22861165
TI  - p53 orchestrates the PGC-1alpha-mediated antioxidant response upon mild redox and
      metabolic imbalance.
AB  - AIMS: The transcriptional coactivator peroxisome proliferator-activated receptor
      gamma coactivator-1 alpha (PPARGC1A or PGC-1alpha) is a powerful controller of
      cell metabolism and assures the balance between the production and the scavenging
      of pro-oxidant molecules by coordinating mitochondrial biogenesis and the
      expression of antioxidants. However, even though a huge amount of data referring
      to the role of PGC-1alpha is available, the molecular mechanisms of its
      regulation at the transcriptional level are not completely understood. In the
      present report, we aim at characterizing whether the decrease of antioxidant
      glutathione (GSH) modulates PGC-1alpha expression and its downstream metabolic
      pathways. RESULTS: We found that upon GSH shortage, induced either by its
      chemical depletion or by metabolic stress (i.e., fasting), p53 binds to the
      PPARGC1A promoter of both human and mouse genes, and this event is positively
      related to increased PGC-1alpha expression. This effect was abrogated by
      inhibiting nitric oxide (NO) synthase or guanylate cyclase, implicating NO/cGMP
      signaling in such a process. We show that p53-mediated PGC-1alpha upregulation is
      directed to potentiate the antioxidant defense through nuclear factor (erythroid
      derived 2)-like2 (NFE2L2)-mediated expression of manganese superoxide dismutase
      (SOD2) and gamma-glutamylcysteine ligase without modulating mitochondrial
      biogenesis. INNOVATION AND CONCLUSIONS: We outlined a new NO-dependent signaling
      axis responsible for survival antioxidant response upon mild metabolic stress
      (fasting) and/or oxidative imbalance (GSH depletion). Such signaling axis could
      become the cornerstone for new pharmacological or dietary approaches for
      improving antioxidant response during ageing and human pathologies associated
      with oxidative stress.

PMID- 22861167
TI  - Neoadjuvant intralesional methotrexate before surgical treatment of invasive
      squamous cell carcinoma of the lower lip.

PMID- 22861168
TI  - Effect of collagen type I or type II on chondrogenesis by cultured human
      articular chondrocytes.
AB  - INTRODUCTION: Current cartilage repair procedures using autologous chondrocytes
      rely on a variety of carriers for implantation. Collagen types I and II are
      frequently used and valuable properties of both were shown earlier in vitro,
      although a preference for either was not demonstrated. Recently, however,
      fibrillar collagens were shown to promote cartilage degradation. The goal of this
      study was to evaluate the effects of collagen type I and type II coating on
      chondrogenic properties of in vitro cultured human chondrocytes, and to
      investigate if collagen-mediated cartilage degradation occurs. METHODS: Human
      chondrocytes of eight healthy cartilage donors were isolated, expanded, and
      cultured on culture well inserts coated with either collagen type I, type II, or
      no coating (control). After 28 days of redifferentiation culture, safranin O and
      immunohistochemical staining for collagen types I, II, X, and Runx2/Cbfa1 were
      performed and glycosaminoglycan (GAG) and DNA content and release were examined.
      Further, expression of collagen type I, type II, type X, MMP13, Runx2/Cbfa1,
      DDR2, alpha2 and beta1 integrin were examined by reverse transcriptase-polymerase
      chain reaction. RESULTS: The matrix, created by chondrocytes grown on collagen
      type I- and II-coated membranes, resembled cartilage more than when grown on
      noncoated membranes as reflected by histological scoring. Immunohistochemical
      staining did not differ between the conditions. GAG content as well as GAG/DNA
      were higher for collagen type II-coated cartilage constructs than control. GAG
      release was also higher on collagen type I- and II-coated constructs. Expression
      of collagen type X was higher of chondrocytes grown on collagen type II compared
      to controls, but no collagen X protein could be demonstrated by
      immunohistochemistry. No effects of collagen coating on DDR2 nor MMP-13 gene
      expression were found. No differences were observed between collagen types I and
      II. CONCLUSION: Chondrocyte culture on collagen type I or II promotes more active
      matrix production and turnover. No significant differences between collagen types
      I and II were observed, nor were hypertrophic changes more evident in either
      condition. The use of collagen type I or II coating for in vitro models, thus,
      seems a sound basis for in vivo repair procedures.

PMID- 22861169
TI  - Maternal education preferences moderate the effects of mandatory employment and
      education programs on child positive and problem behaviors.
AB  - Grounded in person-environment fit theory, this study examined whether low-income
      mothers' preferences for education moderated the effects of employment- and
      education-focused welfare programs on children's positive and problem behaviors.
      The sample included 1,365 families with children between ages 3 and 5 years at
      study entry. Results 5 years after random assignment, when children were ages 8
      10 years, indicated that mothers' education preferences did moderate program
      impacts on teacher-reported child behavior problems and positive behavior.
      Children whose mothers were assigned to the education program were rated by
      teachers to have less externalizing behavior and more positive behavior than
      children whose mothers were assigned to the employment program but only when
      mothers had strong preferences for education.

PMID- 22861170
TI  - Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative
      PCR.
AB  - Macaques are commonly used in biomedical research as animal models of human
      disease. The ABO phenotype of donors and recipients plays an important role in
      the success of transplantation and stem cell research of both human and macaque
      tissue. Traditional serological methods for ABO phenotyping can be time
      consuming, provide ambiguous results and/or require tissue that is unavailable or
      unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of
      macaques using real-time quantitative polymerase chain reaction. This method
      enables the simple and rapid screening of these phenotypes in macaques without
      the need for fresh blood or saliva. This study reports the distribution of the A,
      B, and AB phenotypes of captive cynomolgus macaques that, while regionally
      variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus
      macaques, predominates in cynomolgus macaques and its frequency distribution
      leads to a probability of major incompatibility of 41%. No silencing mutations
      have been identified in exon 6 or 7 in macaques that could be responsible for the
      O phenotype, that, although rare, have been reported. The excess homozygosity of
      rhesus and cynomolgus macaque genotypes in this study, that assumes the absence
      of the O allele, suggests the possibility of some mechanism preventing the
      expression of the A and B transferases.

PMID- 22861172
TI  - Non-resonant dynamic Stark control at a conical intersection: the
      photodissociation of ammonia.
AB  - Control of the photodissociation of ammonia, by the nonresonant dynamic Stark
      effect, has been studied theoretically by the numerically exact propagation of
      wavepackets on ab initio potential energy surfaces. An assessment of the
      feasibility of controlling the proportion of the wavepacket which dissociates to
      produce ground or electronically excited state NH(2) fragments, mediated by a
      conical intersection, has been made by use of a simple two-dimensional, two-state
      model. It was found that modest control was possible for nonresonant pulses
      applied during and after excitation, and that the control was caused not by
      alteration of the position or nature of the conical intersection but by
      modification of the energy surfaces around the Franck-Condon region. This is made
      possible by the predissociative nature of the mechanism for hydrogen ejection.
      The control effect is frequency independent but dependent on pulse, i.e.,
      electric field, strength, indicating that it is indeed due to the Stark effect.
      Analysis of the control is, however, complicated by the presence of vibrational
      effects which can come into play if the control pulse frequency is not carefully
      chosen. By systematically varying the excitation energy, it was also found that
      the capacity for control is only significant at low energies.

PMID- 22861171
TI  - A pilot randomized controlled trial of a decision support tool to improve the
      quality of communication and decision-making in individuals with atrial
      fibrillation.
AB  - OBJECTIVES: To design a tool for nonvalvular atrial fibrillation (NVAF) to inform
      individuals of their individual stroke and bleeding risks, assist in clarifying
      priorities, and promote communication. DESIGN: Clustered randomized controlled
      trial. SETTING: Primary care clinics. PARTICIPANTS: Individuals with NVAF (N =
      135). INTERVENTION: Completion of tool before regularly scheduled visit.
      MEASUREMENTS: Primary outcomes included the 100-point informed and values clarity
      subscales of the decisional conflict scale (lower scores indicate individual is
      more informed and has greater clarity). Secondary outcomes included knowledge,
      patient-clinician communication, and change in treatment. RESULTS: Sixty-nine
      individuals were enrolled in the intervention group and 66 in the control group.
      After their visit, intervention participants had lower scores on the informed
      (mean difference = -11.9, 95% confidence interval (CI) = -21.1 to -2.7) and
      values clarity subscales (mean difference = -14.6, 95% CI = -22.6 to -6.6).
      Greater proportions of intervention participants knew medications for reducing
      stroke risk (61% vs 31%, P < .001) and side effects (49% vs 37%, P = .07). Stroke
      (71% vs 12%) and bleeding risk (69% vs 20%) were discussed more frequently in the
      intervention than control group (P < .001). Five intervention participants
      expressed a preference for medication that was not concordant with their current
      treatment plan. There was no change in treatment plan in either group.
      CONCLUSION: The tool was effective in improving perceived and actual knowledge
      and values clarity and in increasing physician-patient communication but did not
      change treatment.

PMID- 22861173
TI  - A practical and general Diels-Alder reaction of pentafulvenes with arynes.
AB  - A high-yielding, versatile and practical Diels-Alder reaction of pentafulvenes
      with arynes under mild reaction conditions is reported. The aryne generated by
      the fluoride induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates
      undergoes efficient cycloaddition with 6-substituted and 6,6-disubstituted
      pentafulvenes leading to the formation of benzonorbornadiene derivatives.

PMID- 22861174
TI  - Simultaneous monitoring of protein adsorption kinetics using a quartz crystal
      microbalance and field-effect transistor integrated device.
AB  - We developed an integrated device comprising a quartz crystal microbalance (QCM)
      and a field-effect transistor (FET) with a single common gold electrode in a flow
      chamber. An alternating current inducing oscillations in the piezoelectric quartz
      of the QCM sensor is electrically independent of the circuit for the FET output
      so that the two sensors in different detection mechanisms simultaneously record
      binding kinetics from a single protein solution on the same electrode. A
      conjunction of adsorbed mass from QCM with electric nature of bound protein from
      FET provided deeper understanding on a complex process of nonspecific protein
      adsorption and subsequent conformational changes at a solid/liquid interface.
      Lower apparent k(on) values obtained by FET than those obtained by QCM on
      hydrophobic surfaces are interpreted as preferred binding of protein molecules
      facing uncharged domains to the electrode surface, whereas higher k(off) values
      by FET than those by QCM imply active macromolecular rearrangements on the
      surfaces mainly driven by hydrophobic association in an aqueous medium. The
      advanced features of the combined sensor including in situ, label-free, and real
      time monitoring provide information on structural dynamics, beyond measurements
      of affinities and kinetics in biological binding reactions.

PMID- 22861175
TI  - Fathers' thoughts on breastfeeding and implications for a theory-based
      intervention.
AB  - OBJECTIVE: To explore male partner's perceptions of breastfeeding to inform the
      development of interventions to increase their support of breastfeeding. DESIGN:
      Qualitative grounded theory. SETTING: Participants were recruited and interviewed
      in two Special Supplemental Nutrition Program for Women, Infants and Children
      (WIC) clinics located Honolulu, Hawai'i. PARTICIPANTS: Fourteen male partners of
      low-income pregnant women or new mothers. METHODS: Male partner attitudes,
      knowledge, and feelings were collected through private interviews. Interviews
      were transcribed verbatim and data were analyzed using grounded theory methods.
      RESULTS: All men appreciated breastfeeding's health benefits, acknowledged that
      it was natural, and were empathetic to the efforts of their partners. The men
      also discussed not being involved in the breastfeeding decision, believing
      formula feeding was more convenient than breastfeeding, feeling left out of the
      infant-feeding process, and being uncomfortable with breastfeeding in public.
      CONCLUSIONS: Findings suggest that an intervention to increase male partner
      support of breastfeeding should include multiple components to enhance knowledge,
      to empower men to be more engaged in the breastfeeding decision, to provide
      specific tips on how men can be involved in breastfeeding, and to increase
      comfort with breastfeeding in public. A multicomponent framework such as the
      social cognitive theory could be useful in guiding the development of such an
      intervention.

PMID- 22861176
TI  - Long-acting formulation of a new muscarinic receptor antagonist for the treatment
      of overactive bladder.
AB  - A new muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (5-HMT), was
      successfully encapsulated into PLGA microspheres. With an increase of PLGA
      concentration from 15% to 40%, encapsulation efficiency of 5-HMT increased from
      55.39% to 76.32%, and the particle size of microsphere increased from 34.33 to
      70.48 um. Increasing the homogenisation speed from 850 to 2300 rpm, the particle
      size was reduced about 65%.The in vitro and in vivo studies in beagle dogs show
      that the release profile of 5-HMT-loaded microspheres (5-HMT MS) prepared with
      503H is characterised by a low initial burst followed by slow release that lasted
      for 2 weeks. A C(max) of 1.617 +/- 0.392 ng/mL was found on the sixth day. When
      evaluated for inhibition of the carbachol-induced contraction of rat urinary
      bladder, 5-HMT MS showed a much longer and more potent effect than tolterodine
      tablets. The mean urination time of the rats in the 5-HMT MS group was
      significantly decreased (p < 0.05 or p < 0.01) to less than 2 weeks.

PMID- 22861177
TI  - Pressure-induced changes in the fluorescence behavior of red fluorescent
      proteins.
AB  - We present an experimental study on the fluorescence behavior of the red
      fluorescent proteins TagRFP-S, TagRFP-T, mCherry, mOrange2, mStrawberry, and mKO
      as a function of pressure up to several GPa. TagRFP-S, TagRFP-T, mOrange2, and
      mStrawberry show an initial increase in fluorescence intensity upon application
      of pressure above ambient conditions. At higher pressures, the fluorescence
      intensity decreases dramatically for all proteins under study, probably due to
      denaturing of the proteins. Small blue shifts in the fluorescence spectra with
      increasing pressure were seen in all proteins under study, hinting at increased
      rigidity of the chromophore environment. In addition, mOrange2 and mStrawberry
      exhibit strong and abrupt changes in their fluorescence spectra at certain
      pressures. These changes are likely due to structural modifications of the
      hydrogen bonding environment of the chromophore. The strong differences in
      behavior between proteins with identical or very similar chromophores highlight
      how the chromophore environment contributes to pressure-induced behavior of the
      fluorescence performance. 

PMID- 22861178
TI  - Guiding the next generation of NIH investigators in responsible conduct of
      research: the role of the mentor.
AB  - National Institutes of Health (NIH) K award recipients and their mentors were
      surveyed to investigate the role of the mentor. We found that a majority of
      mentors provided guidance in responsible research conduct (RCR), and that most of
      these relationships were deemed helpful. Mentors also responded that they played
      a greater importance in RCR training of their mentees than the mentees reported.
      Our results suggest both mentors and mentees report that mentors ideally should
      play a more important role in RCR training than was actually the case. For
      conflicting interests, subjects' protection, and misconduct, approximately 50% of
      K recipients found the mentor to be not at all important or only somewhat
      important for these areas of RCR training. We conclude the mentor's role is
      important but not optimal based on the results of our study cohort.

PMID- 22861179
TI  - Research integrity and conflicts of interest: the case of unethical research
      misconduct charges filed by Edward Calabrese.
AB  - Special-interest polluters often file research-misconduct (RM) charges against
      scientists whose research suggests needed pollutant regulation. This article
      argues that U.S. RM regulations are flawed in requiring RM
      assessors/experts/accused, but not accusers, to reveal possible conflicts of
      interest (COI) that could affect RM allegations. It (1) summarizes U.S. RM
      regulatory history; (2) uses a case study about 2011 RM allegations, filed by
      chemical-industry-funded toxicologist Edward Calabrese, to illustrate problems
      with RM regulations; and (3) offers 4 arguments in favor of revising RM
      regulations so as to require RM-accuser revelation of possible COI and who funded
      preparation of the RM allegations.

PMID- 22861180
TI  - COI policies: tax dollars should not be used to fund U.S. institutions not making
      the grade.
AB  - Over two billion dollars was awarded by the U.S. Department of Health and Human
      Services (HHS) in research funding from 2010 to March 2012 to institutions
      receiving a grade of "C," "D," or "F" on their conflict of interest policies, as
      determined by the American Medical Student Association's scorecard on conflict of
      interest policies. More institutional oversight is needed with regard to assuring
      conflict of interest policies at U.S. research institutions are adequate. As
      stewards of public funds, HHS should require a minimum standard which
      institutional conflict of interest policies should meet, beyond current
      regulatory requirements, before granting funding.

PMID- 22861181
TI  - RCR online course: build an online course to augment RCR training using evidenced
      based learning theory.
AB  - This article demonstrates how to apply evidenced-based instructional design
      principles to develop a supplemental, online Responsible Conduct of Research
      (RCR) course. The supplement RCR course may serve to appropriately augment the
      National Institutes of Health (NIH) required RCR training. The way to ensure that
      an online RCR course is effective is to incorporate evidence-based learning
      theories into the development of the course content. This article specifically
      demonstrates application of Bloom's taxonomy and Gagne's Nine Instructional
      Events to a research misconduct course. At the conclusion, the reader will be
      able to apply evidence-based learning theories to the development of any online
      course.

PMID- 22861182
TI  - Letter to the editor: reviewers.

PMID- 22861183
TI  - The role of roots in the resource economics spectrum.

PMID- 22861184
TI  - Ectomycorrhiza and the open nitrogen cycle in an afrotropical rainforest.

PMID- 22861185
TI  - Strigolactones affect development in primitive plants. The missing link between
      plants and arbuscular mycorrhizal fungi?

PMID- 22861186
TI  - Xylem plasticity in response to climate.

PMID- 22861187
TI  - Initial application of reduced port surgery using the single port access
      technique for laparoscopic canine ovariectomy.
AB  - OBJECTIVE: To describe the Single port access (SPA) laparoscopic entry technique
      for canine ovariectomy (OVE), report complications, and outcomes. STUDY DESIGN:
      Pilot study. ANIMALS: Intact female dogs (n = 6). METHODS: With owner consent, 6
      intact female dogs had SPA laparoscopic OVE. Data, including signalment, surgical
      time (from incision to completion of closure), size and location of port
      placement, need for conversion (both to standard multiport laparoscopy and
      laparotomy), as well as any intraoperative complications including blood loss or
      tissue injury were recorded. RESULTS: Mean surgical time was 52.5 minutes (range,
      45-60 minutes) and mean incision length, 1.8 cm (range, 1.5-2.0 cm). In an 18-kg
      mix breed dog (dog 3), a "single port rescue" was required and located on midline
      2-cm caudal to the umbilicus. Close positioning of the trocars caused instrument
      interference, limited viewing, and prevented safe ligation of the ovarian vessels
      vein with a vessel-sealing device. OVE was successfully completed
      laparoscopically in all dogs. CONCLUSION: The SPA laparoscopic entry technique
      can be used in dogs, although instrument and camera interference can occur if
      trocar placement is too consolidated within the initial skin incision.

PMID- 22861188
TI  - Atomic-scale morphology and electronic structure of manganese atomic layers
      underneath epitaxial graphene on SiC(0001).
AB  - We report the fabrication of a novel epitaxial graphene(EG)/Mn/SiC(0001)
      sandwiched structure through the intercalation of as-deposited Mn atoms on
      graphene surfaces, with the aid of scanning tunneling microscope, low energy
      electron diffraction, and X-ray photoelectron spectroscopy. We found that Mn can
      intercalate below both sp(3)-hybridized carbon-rich interface layer and monolayer
      graphene, along with the formation of various embedded Mn islands showing
      different surface morphologies. The unique trait of the sandwiched system is that
      the strong interaction between the carbon-rich interface layer and SiC(0001) can
      be decoupled to some degrees, and contemporaneous, an n-doping effect is observed
      by mapping the energy band of the system using angle-resolved photoemission
      spectroscopy. Moreover, what deserves our special attention is that the
      intercalated islands can only evolve below monolayer graphene when a bilayer
      coexists, accounting for an intriguing graphene thickness-dependent intercalation
      effect. In the long run, we believe that the construction of
      graphene/Mn/SiC(0001) systems offers ideal candidates for exploring some
      intriguing physical properties such as the magnetic property of two-dimensional
      transition metal systems.

PMID- 22861189
TI  - Targeting hepatoma using nitric oxide donor strategies.
AB  - AIMS: The study evaluated the role of increased intracellular nitric oxide (NO)
      concentration using NO donors or stably NO synthase-3 (NOS-3) overexpression
      during CD95-dependent cell death in hepatoma cells. The expression of cell death
      receptors and caspase activation, RhoA kinase activity, NOS-3
      expression/activity, oxidative/nitrosative stress, and p53 expression were
      analyzed. The antitumoral activity of NO was also evaluated in the subcutaneous
      implantation of NOS-3-overexpressing hepatoma cells, as well NO donor injection
      into wild-type hepatoma-derived tumors implanted in xenograft mouse models.
      RESULTS: NO donor increased CD95 expression and activation of caspase-8 and 3 in
      HepG2, Huh7, and Hep3B cells. NOS-3 overexpression increased
      oxidative/nitrosative stress, p53 and CD95 expression, cellular Fas-associated
      death domain (FADD)-like IL-1beta converting enzyme (FLICE) inhibitory protein
      long (cFLIP(L)) and its short isoform (cFLIP(S)) shift, and cell death in HepG2
      (4TO-NOS) cells. The inhibition of RhoA kinase and p53 knockdown using RNA
      interference reduced cell death in 4TO-NOS cells. The supplementation with
      hydrogen peroxide (H(2)O(2)) increased NOS-3 activity and cell death in 4TO-NOS
      cells. NOS-3 overexpression or NO donor injection into hepatoma-derived tumors
      reduced the size and increased p53 and cell death receptor expression in nude
      mice. INNOVATION AND CONCLUSIONS: The increase of intracellular NO concentration
      promoted oxidative and nitrosative stress, Rho kinase activity, p53 and CD95
      expression, and cell death in cultured hepatoma cells. NOS-3-overexpressed HepG2
      cells or intratumoral NO donor administration reduced tumor cell growth and
      increased the expression of p53 and cell death receptors in tumors developed in a
      xenograft mouse model.

PMID- 22861190
TI  - Identification of contact sites between ankyrin and band 3 in the human
      erythrocyte membrane.
AB  - The red cell membrane is stabilized by a spectrin/actin-based cortical
      cytoskeleton connected to the phospholipid bilayer via multiple protein bridges.
      By virtue of its interaction with ankyrin and adducin, the anion transporter,
      band 3 (AE1), contributes prominently to these bridges. In a previous study, we
      demonstrated that an exposed loop comprising residues 175-185 of the cytoplasmic
      domain of band 3 (cdB3) constitutes a critical docking site for ankyrin on band
      3. In this paper, we demonstrate that an adjacent loop, comprising residues 63-73
      of cdB3, is also essential for ankyrin binding. Data that support this hypothesis
      include the following. (1) Deletion or mutation of residues within the latter
      loop abrogates ankyrin binding without affecting cdB3 structure or its other
      functions. (2) Association of cdB3 with ankyrin is inhibited by competition with
      the loop peptide. (3) Resealing of the loop peptide into erythrocyte ghosts
      alters membrane morphology and stability. To characterize cdB3-ankyrin
      interaction further, we identified their interfacial contact sites using
      molecular docking software and the crystal structures of D(3)D(4)-ankyrin and
      cdB3. The best fit for the interaction reveals multiple salt bridges and
      hydrophobic contacts between the two proteins. The most important ion pair
      interactions are (i) cdB3 K69-ankyrin E645, (ii) cdB3 E72-ankyrin K611, and (iii)
      cdB3 D183-ankyrin N601 and Q634. Mutation of these four residues on ankyrin
      yielded an ankyrin with a native CD spectrum but little or no affinity for cdB3.
      These data define the docking interface between cdB3 and ankyrin in greater
      detail.

PMID- 22861191
TI  - Anti-infection tissue engineering construct treating osteomyelitis in rabbit
      tibia.
AB  - Bone defect complicated by infection remains a major challenge in orthopedic
      surguries, and bone grafting for primary repair often associates with high
      failure rate. The rapid progress in the research spectrums of tissue-engineered
      bone and antibiotic delivery systems bring hope to solve this issue. Herein, we
      evaluated the local anti-infective and osteogenic potential of an injectable anti
      infection tissue-engineered construct, which includes a fibrin gel scaffold and
      vancomycin alginate beads (Vanco-AB) to form composites, in the treatment of
      chronic osteomyelitis with bone defect in rabbit tibia. The infected bone defect
      model of rabbit tibia was established. Then, the bone defects in the proximal
      tibial metaphysis were implanted with the constructed composites, containing
      different combinations of mesenchymal stem cells and Vanco-AB. The in vivo
      capacities of anti-infection and local osteogenesis of the grafts were determined
      using radiographic assessment, histopathological observation, and microorganism
      cultures. Results showed that the injectable anti-infection tissue-engineered
      construct, comprising a fibrin gel scaffold and Vanco-AB led to efficient
      eradication of bacteria. At 1 and 3 months after transplantation, the
      radiographic assessment and microbiological examination demonstrated that the
      sustained antibiotic release by Vanco-AB significantly decreased the Norden
      scores of osteomyelitis, generated negative results for the presence of bacteria,
      and reduced the relapse of osteomyelitis. Meanwhile, tissue-engineered construct
      implanted in one-stage promoted local bone repair and reconstruction, and it
      exhibited more apparent osteogenic potential, compared to the control group
      (without Vanco-AB). In conclusion, the current study achieved the primary repair
      of bone defect with infection, thus providing an alternative treatment strategy
      for infected bone defect, which occurs commonly in chronic osteomyelitis.

PMID- 22861192
TI  - A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal
      antibody administered intravenously to patients with relapsed or refractory
      multiple myeloma.
AB  - In this open-label, multicentre, phase 1 study a fully human anti-CD40 antagonist
      monoclonal antibody, lucatumumab, was evaluated in patients with
      relapsed/refractory multiple myeloma (MM). The primary objective was to determine
      the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs).
      Secondary objectives included safety, pharmacokinetics, pharmacodynamics and
      antimyeloma activity. Twenty-eight patients, enrolled using a standard '3 + 3'
      dose escalation, received one or two (n = 3) cycles of lucatumumab 1.0, 3.0, 4.5
      or 6.0 mg/kg once weekly for 4 weeks. Common lucatumumab-related adverse events
      were reversible, mild-to-moderate infusion reactions. Severe adverse events were
      anaemia, chills, hypercalcaemia and pyrexia (7% each). DLTs included grade 4
      thrombocytopenia, grade 3 increased alanine aminotransferase and grade 4
      increased lipase (n = 1 each). The MTD was 4.5 mg/kg. At doses >=3.0 mg/kg,
      sustained receptor occupancy (>=87%), observed throughout weekly infusions up to
      5 weeks after the last infusion, correlated with an estimated half-life of 4-19
      d. Twelve patients (43%) had stable disease, and one patient (4%) maintained a
      partial response for >=8 months. These findings indicate that single-agent
      lucatumumab was well tolerated up to 4.5 mg/kg with modest clinical activity in
      relapsed/refractory MM, warranting further study as a combination therapy.

PMID- 22861193
TI  - Selective dual inhibitors of CYP19 and CYP11B2: targeting cardiovascular diseases
      hiding in the shadow of breast cancer.
AB  - Postmenopausal women are at high risk for cardiovascular diseases because of the
      estrogen deficiency. As for postmenopausal breast cancer patients, this risk is
      even higher due to inhibition of estrogens biosyntheses in peripheral tissue by
      the aromatase (CYP19) inhibitors applied. Because estrogen deficiency results in
      significantly elevated aldosterone levels, which are a major cause of
      cardiovascular diseases, dual inhibition of CYP19 and CYP11B2 (aldosterone
      synthase) is a promising treatment for breast cancer and the coinstantaneous
      cardiovascular diseases. By combination of important structural features of known
      CYP19 and CYP11B2 inhibitors, we succeeded in obtaining compounds 3 and 5 as
      selective dual inhibitors with IC(50) values around 50 and 20 nM toward CYP19 and
      CYP11B2, respectively. These compounds showed also good selectivity toward
      CYP11B1 (selectivity factors (IC(50 CYP11B1)/IC(50 CYP11B2)) around 50) and CYP17
      (no inhibition).

PMID- 22861194
TI  - Pullout-proofing external ventricular drains.
AB  - OBJECT: The authors describe a method of securing an external ventricular drain
      (EVD) to prevent dislodgement and discourage CSF leakage and infection. METHODS:
      The EVD is secured using a single permanent suture, creating a box stitch around
      the exit site attached to a modified roman sandal. Multiple knots are tied after
      each loop to avoid "telescoping," loosening, and pullout. RESULTS: In 12 years of
      high-volume pediatric practice by one of the authors, only one drain has broken,
      and none have pulled out. CONCLUSIONS: The modified roman sandal technique
      tightly secures EVDs against pullout. Anecdotal evidence suggests that the
      strength of the suture construct securing the drain is greater than that of the
      drain tubing itself.

PMID- 22861195
TI  - Optimal timing of autologous cranioplasty after decompressive craniectomy in
      children.
AB  - OBJECT: The object of this study was to determine if early cranioplasty after
      decompressive craniectomy for elevated intracranial pressure in children reduces
      complications. METHODS: Sixty-one consecutive cases involving pediatric patients
      who underwent autologous cranioplasty after decompressive craniectomy for raised
      intracranial pressure at a single academic children's hospital over 15 years were
      studied retrospectively. RESULTS: Sixty-one patients were divided into early (< 6
      weeks; 28 patients) and late (>= 6 weeks; 33 patients) cranioplasty cohorts. The
      cohorts were similar except for slightly lower age in the early (8.03 years) than
      the late (10.8 years) cranioplasty cohort (p < 0.05). Bone resorption after
      cranioplasty was significantly more common in the late (42%) than the early (14%)
      cranioplasty cohort (p < 0.05; OR 5.4). No other complication differed in
      incidence between the cohorts. CONCLUSIONS: After decompressive craniectomy for
      raised intracranial pressure in children, early (< 6 weeks) cranioplasty reduces
      the occurrence of reoperation for bone resorption, without altering the incidence
      of other complications.

PMID- 22861196
TI  - Intraventricular baclofen as an alternative to intrathecal baclofen for
      intractable spasticity or dystonia: outcomes and technical considerations.
AB  - OBJECT: The aim of this study was to identify the benefits of intraventricular
      baclofen (IVB) therapy for the treatment of intractable spasticity or dystonia in
      a subset of patients who had experienced multiple revisions while receiving
      intrathecal baclofen (ITB) therapy. METHODS: The authors reviewed the charts of
      22 consecutive patients with intractable spasticity or dystonia who initially
      underwent ITB therapy, subsequently suffered multiple revisions during ITB
      therapy, and ultimately received IVB therapy, all during a 12-year period from
      November 1998 to October 2010. The intraventricular catheters were positioned in
      the lateral ventricle, aided by stereonavigation. RESULTS: The surgical revision
      rate (the average number of surgical revisions per average number of follow-up
      years) during ITB therapy was 0.84, and was 0.50 during IVB therapy. The most
      frequent complication requiring surgical revision during ITB therapy was catheter
      occlusion, followed by pump malfunction/pump pocket issues, and infection. The
      most frequent complication requiring surgical revision during IVB therapy was
      infection, followed by catheter misplacement/migration. Four patients suffered
      infection that required removal of their intraventricular catheter, and currently
      have no baclofen system. CONCLUSIONS: Some of these patients had a history of
      increasing revisions with increasing frequency during ITB therapy. Such a history
      puts them at risk for spinal arachnoiditis, a condition that complicates further
      ITB therapy. For such patients, the authors believe that IVB therapy may be a
      beneficial therapeutic option, given that the surgical revision rate was lower
      for IVB than for ITB. Intraventricular baclofen may be a cost-effective option
      for patients with mounting revisions during ITB therapy.

PMID- 22861197
TI  - Two-level thoracic pedicle subtraction osteotomy for progressive post-laminectomy
      kyphotic deformity following resection of an unusual thoracolumbar intradural
      extramedullary tumor.
AB  - The authors report a case in which multilevel thoracic pedicle subtraction
      osteotomy (PSO) was performed to correct post-laminectomy kyphotic deformity in a
      9-year-old boy presenting with worsening lower-extremity neurological deficits.
      Five years prior to presentation, the patient underwent multilevel thoracolumbar
      laminectomies for resection of an atypical teratoid/rhabdoid tumor (AT/RT), a
      rare lesion that typically occurs intracranially and has a poor prognosis, making
      this particular presentation unusual and the patient's subsequent postoperative
      course remarkable. No fusion was undertaken at the time of resection, given the
      patient's age and presumptive poor prognosis. Over the next 5 years, the patient
      developed progressive thoracolumbar kyphotic deformity, with a Cobb angle greater
      than 110 degrees , despite bracing, and bilateral lower-extremity weakness
      requiring ankle-foot orthotics for continued ambulation due to progressive foot
      drop. Worsening gait and the onset of respiratory issues prompted surgical
      intervention. Multilevel thoracic PSO and thoracolumbar fusion were performed,
      resulting in improved lower-extremity function and correction of the kyphotic
      deformity to approximately 65 degrees . This report outlines an unusual AT/RT
      presentation and postoperative course and also discusses literature related to
      PSO within the context of pediatric kyphotic deformity. The authors' experience
      supports the use of multilevel PSO with fusion as a potential treatment option
      for significant pediatric thoracolumbar kyphotic deformity requiring surgical
      correction.

PMID- 22861198
TI  - Effects of ionized waterfall aerosol on pediatric allergic asthma.
AB  - OBJECTIVE: Ionized water aerosols have been suggested to exert beneficial health
      effects on pediatric allergic asthma. Their effect was evaluated in a randomized
      controlled clinical trial as part of a summer asthma camp. METHODS: Asthmatic
      allergic children (n = 54) spent 3 weeks in an alpine asthma camp; half of the
      group was exposed to water aerosol of an alpine waterfall for 1 hour per day,
      whereas the other half spent the same time at a "control site". Immunological
      analysis, lung function testing, and fractional exhaled nitric oxide (FeNO)
      testing were performed during the stay, and sustaining effects were evaluated 2
      months later. Symptom score testing was done over a period of 140 days. RESULTS:
      The water aerosol group showed a significant improvement in all lung function
      parameters, whereas only the peak expiratory flow improved in the control group.
      All patients showed a significant improvement in symptom score and a significant
      decrease in FeNO after the camp. Only the water aerosol group exhibited a long
      lasting effect on asthma symptoms, lung function, and inflammation in the follow
      up examination. Induction of interleukin (IL)-10 and regulatory T (Treg) cells
      was measured in both groups, with a pronounced increase in the water aerosol
      group. IL-13 was significantly decreased in both groups, whereas IL-5 and
      eosinophil cationic protein were decreased only in the water aerosol group.
      CONCLUSIONS: Our findings confirm the induction of Treg cells and reduction in
      inflammation by climate therapy. They indicate a synergistic effect of water
      aerosols resulting in a long-lasting beneficial effect on asthma symptoms, lung
      function, and airway inflammation.

PMID- 22861199
TI  - Statistical thermodynamics of long straight rigid rods on triangular lattices:
      nematic order and adsorption thermodynamic functions.
AB  - The statistical thermodynamics of straight rigid rods of length k on triangular
      lattices was developed on a generalization in the spirit of the lattice-gas model
      and the classical Guggenheim-DiMarzio approximation. In this scheme, the
      Helmholtz free energy and its derivatives were written in terms of the order
      parameter, delta, which characterizes the nematic phase occurring in the system
      at intermediate densities. Then, using the principle of minimum free energy with
      delta as a parameter, the main adsorption properties were calculated. Comparisons
      with Monte Carlo simulations and experimental data were performed in order to
      evaluate the outcome and limitations of the theoretical model.

PMID- 22861200
TI  - Gastric carcinoids after long-term use of a proton pump inhibitor.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid
      secretion and give hypergastrinemia secondary to gastric hypoacidity. PPI
      treatment therefore induces enterochromaffin-like (ECL) cell hyperplasia. Long
      term hypergastrinemia in rodents and man also leads to ECL cell neoplasia.
      Whether long-term PPI treatment will induce ECL cell neoplasia in man has been
      disputed. AIM: To describe gastric carcinoids in two patients with a history of
      long-term PPI use. RESULTS: Two patients had been taking PPI for 12-13 years due
      to gastro-oesophageal reflux disease. At routine upper gastrointestinal endoscopy
      a solitary tumour was found in the oxyntic mucosa of both patients. Histology
      from the tumours showed in both cases a well-differentiated neuroendocrine
      tumour. Biopsies from flat oxyntic mucosa showed no signs of atrophic gastritis
      and a normal presence of parietal cells in both cases, but hyperplasia of ECL
      cells. The tumour in patient 1 was resected endoscopically. After cessation of
      PPI treatment the tumour regressed in patient 2 and the ECL cell hyperplasia
      regressed in both patients. In patient 2 serum gastrin and chromogranin A were
      elevated during PPI treatment, and normalised after cessation of treatment. In
      patient 1, unfortunately, we had serum only after treatment, and at that time
      both parameters were normal. CONCLUSION: These cases show that hypergastrinemia
      secondary to proton pump inhibitors treatment, like other causes of
      hypergastrinemia, may induce enterochromaffin-like cell carcinoids in man.

PMID- 22861348
TI  - Development of vascular risk factors over 15 years in relation to cognition: the
      Hoorn Study.
AB  - OBJECTIVES: To investigate the development of vascular risk factor levels at four
      points over 15 years in relation to late-life cognitive functioning. DESIGN:
      Longitudinal population-based study. SETTING: The Hoorn Study, a community-based
      cohort study of glucose metabolism and cardiovascular risk. PARTICIPANTS: Three
      hundred eighty individuals without dementia (mean baseline age 57.7 +/- 5.5).
      MEASUREMENTS: Four extensive medical examinations were conducted over 15 years.
      Cognition was assessed in detail at the fourth examination. The time course of
      vascular risk factors across the examinations was compared between individuals in
      the highest tertile (good performance) and those in the lowest tertile (poor
      performance) of cognitive functioning on three cognitive domains (memory,
      information processing speed, and attention and executive functioning (A&EF)).
      RESULTS: Individuals with poor information processing speed had higher levels of
      systolic blood pressure at baseline (mean difference (standard error) 11.6 (2.6)
      mmHg, P < .001) than those with good information processing speed. Individuals
      with poor A&EF had a higher waist:hip ratio (3.03 (1.15), P = .009), glycosylated
      hemoglobin (0.29% (0.10%), P = .005) and total cholesterol:high-density
      lipoprotein cholesterol ratio (0.38 (0.19), P = .04) at baseline than individuals
      with good A&EF, although the differences in vascular risk factor levels between
      the poor and good cognition group diminished with increasing age. CONCLUSION:
      High blood pressure, adiposity, hypercholesterolemia, and hyperglycemia at
      midlife are associated with late-life cognitive dysfunction, but for most risk
      factors, this relationship gradually attenuates with increasing age. These
      results suggest that timing of vascular treatment strategies to prevent cognitive
      impairment is critical.

PMID- 22861349
TI  - Semiexperimental equilibrium structures for the equatorial conformers of N
      methylpiperidone and tropinone by the mixed estimation method.
AB  - N-Methylpiperidone (MPIP) and tropinone, which contain a structural motif found
      in numerous alkaloids, are too large to determine an accurate equilibrium
      structure either by ab initio methods or by experiment. However, the ground state
      rotational constants of the parent species and of all isotopologues with a
      substituted heavy atom ((13)C, (15)N, (18)O) are known from microwave
      spectroscopy. These constants have been corrected for the rovibrational
      contribution calculated from an ab initio cubic force field. These
      semiexperimental equilibrium rotational constants have been supplemented by
      carefully chosen structural parameters from medium level ab initio calculations.
      The two sets of data have been used in a weighted least-squares fit to determine
      reliable equilibrium structures for both molecules. This work shows that it is
      possible to determine reliable equilibrium structures for large molecules (34
      degrees of freedom in the case of tropinone) at a detailed level of accuracy, and
      the method could be applied without too much difficulty to still larger
      molecules.

PMID- 22861350
TI  - P(II)  signal transduction proteins: nitrogen regulation and beyond.
AB  - The P(II)  proteins are one of the most widely distributed families of signal
      transduction proteins in nature. They are pivotal players in the control of
      nitrogen metabolism in bacteria and archaea, and are also found in the plastids
      of plants. Quite remarkably, P(II)  proteins control the activities of a diverse
      range of enzymes, transcription factors and membrane transport proteins, and in
      recent years the extent of these interactions has been recognized to be much
      greater than heretofore described. Major advances have been made in structural
      studies of P(II)  proteins, including the solution of the first structures of
      P(II)  proteins complexed with their targets. We have also begun to gain insights
      into how the key effector molecules, 2-oxoglutarate and ATP/ADP, influence the
      activities of P(II)  proteins. In this review, we have set out to summarize our
      current understanding of P(II)  biology and to consider where future studies of
      these extraordinarily adaptable proteins might lead us.

PMID- 22861201
TI  - Anti-dyskinetic mechanisms of amantadine and dextromethorphan in the 6-OHDA rat
      model of Parkinson's disease: role of NMDA vs. 5-HT1A receptors.
AB  - Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia
      (LID) in patients with Parkinson's disease (PD) and abnormal involuntary
      movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These
      effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However,
      amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake
      and cause 5-HT overflow, leading to stimulation of 5-HT(1A)  receptors, which has
      been shown to reduce LID. We undertook a study in 6-OHDA rats to determine
      whether the anti-dyskinetic effects of these two compounds are mediated by NMDA
      antagonism and/or 5-HT(1A)  agonism. In addition, we assessed the sensorimotor
      effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and
      Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was
      not affected by the 5-HT(1A)  antagonist WAY-100635, but was partially reversed
      by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of
      dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither
      amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in
      sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is
      partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs
      via indirect 5-HT(1A)  agonism. Combined with previous work from our group, our
      results support the investigation of 5-HT(1A)  agonists as pharmacotherapies for
      LID in PD patients.

PMID- 22861351
TI  - A structured PBL tutorial involving small teams for teaching the human nervous
      system.
AB  - BACKGROUND: The Human Nervous System and Behavior course at Harvard Medical
      School (HMS) incorporates a hybrid model of problem-based learning. Student
      preparation for and participation in the tutorial seemed to be insufficient.
      AIMS: We sought to increase student engagement in tutorial by creating a
      structured approach, which included assigned roles for students, weekly testing,
      formal cornerstone presentations, and a weekly self-assessment exercise. We
      wished to determine the students' and tutors' satisfaction with this structured
      approach as compared with the more traditional tutorial experienced in other
      courses at HMS. METHODS: For the first 4 years of the course, students (n = 160)
      were surveyed concerning their impressions of the quality of the structured
      approach in comparison with the traditional tutorial. In addition, they were
      surveyed concerning the cornerstone presentations and the self-assessment
      exercise. Tutors (n = 10) who had taught in both the traditional and structured
      tutorial formats were surveyed about their impressions of student performance as
      well as their own enjoyment in the structured format. RESULTS: Students and
      tutors found the structured approach superior to the previous method. Both groups
      noted increased student preparation, participation, and accountability. Tutors
      preferred teaching in the structured format. CONCLUSIONS: The structured approach
      increased student accountability, preparation, and participation. Students and
      tutors preferred this tutorial experience over the previous approach.

PMID- 22861352
TI  - Prion protein expression and functional importance in developmental angiogenesis:
      role in oxidative stress and copper homeostasis.
AB  - AIM: It has been convincingly shown that oxidative stress and toxicity by
      deregulated metals, such as copper (Cu), are tightly linked to the development of
      pre-eclampsia and intrauterine growth retardation (IUGR), the most threatening
      pathologies of human pregnancy. However, mechanisms implemented to control these
      effects are far from being understood. Among proteins that bind Cu and insure
      cellular protection against oxidative stress is the cellular prion protein
      (PrP(C)), a glycosyl phosphatidyl inositol-anchored glycoprotein, which we
      reported to be highly expressed in human placenta. Herein, we investigated the
      pathophysiological role of PrP(C) in Cu and oxidative stress homeostasis in vitro
      using human placenta and trophoblast cells, and in vivo using three strains of
      mice (C57Bl6, PrP(C) knockout mice [PrP(-/-)], and PrP(C) overexpressing mice
      [Tga20]). RESULTS: At the cellular level, PrP(C) protection against oxidative
      stress was established in multiple angiogenic processes: proliferation,
      migration, and tube-like organization. For the animal models, lack (PrP(-/-)) or
      overexpression (Tga20) of PrP(C) in gravid mice caused severe IUGR that was
      correlated with a decrease in litter size, changes in Cu homeostasis, increase in
      oxidative stress response, development of hypoxic environment, failure in
      placental function, and maintenance of growth defects of the offspring even 7.5
      months after delivery. INNOVATION: PrP(C) could serve as a marker for the
      idiopathic IUGR disease. CONCLUSION: These findings demonstrate the stress
      protective role of PrP(C) during development, and propose PrP(C) dysregulation as
      a novel causative element of IUGR.

PMID- 22861353
TI  - Predicting the likelihood of suicide attempts for rural outpatients with
      schizophrenia.
AB  - AIMS AND OBJECTIVES: To explore suicide predictors in rural outpatients with
      schizophrenia. Background.  Suicide is a major cause of mortality in patients
      with schizophrenia. Evidence indicates that patients in rural areas are at high
      risk for inadequate health care services. However, information is limited on
      suicide risk in outpatients with schizophrenia in rural areas. DESIGN: Cross
      sectional survey. METHODS: Data were collected on individuals enrolled in the
      2007 Taiwan National Health Insurance program as diagnosed with schizophrenia, >=
      18 years, and living in a rural county. Eligible individuals (n=1655) were
      assessed by 12 community-based nurses at 12 public health centres. Participants'
      personal information was retrieved from National Health Insurance records using a
      personal data sheet, and treatment experiences were obtained by interviewing
      patients with a 10-item risk-assessment inventory. Data were collected over 18
      months (2007-2008) and analysed by descriptive statistics and regression
      analyses. RESULTS: Risk of suicide attempt in the previous year had four
      significant predictors: number of self-harm incidents during the previous year,
      violent incidents towards others during the previous year, number of follow-ups
      by mental health clinics and number of involuntary hospitalisations during the
      previous year (R(2) = 0.337, adjusted R(2) = 0.334, F=133.19, p=0.000).
      CONCLUSION: Health care providers should assess rural outpatients with
      schizophrenia for suicidal thoughts by asking simple questions to evaluate for a
      history of self-harm and violence and by comparing this information with health
      system data on follow-ups by mental health clinics and involuntary
      hospitalisations. RELEVANCE TO CLINICAL PRACTICE: Community-based health
      providers may use these results to prioritise assessments when they have a high
      case load of patients with schizophrenia. Community-based nurses need to be
      trained to recognise these four predictors to increase their sensitivity to
      suicidality among patients with schizophrenia.

PMID- 22861355
TI  - Primary adenocarcinoma of the eyelid with signet ring cell and histiocytoid
      features.

PMID- 22861354
TI  - Mechanical load modulates the stimulatory effect of BMP2 in a rat nonunion model.
AB  - INTRODUCTION: Local application of bone morphogenetic proteins (BMPs) at the
      fracture site is known to stimulate bone regeneration. However, recent studies
      illustrate that the BMP-initiated mineralization may be enhanced by additional
      mechanical stimulation. Therefore, bone healing was monitored in vivo in order to
      investigate the effect of mechanical loading on the initiation and maturation of
      mineralization after cytokine treatment. We hypothesized that the mechanical
      stimulation would further enhance the efficacy of BMP2 treatment. METHOD: Female
      Sprague-Dawley rats underwent a 5-mm defect, stabilized with an external fixator.
      Type I collagen scaffolds containing 50 MUg of BMP2 diluted in a solvent or
      solvent only were placed into the defects. The BMP2-treated specimens and control
      specimens were then each divided into two groups: one that underwent mechanical
      loading and a nonloaded group. In vivo loading began immediately after surgery
      and continued once per week for the entire 6-week experimental period. For all
      groups, the newly formed callus tissue was quantitatively evaluated first by in
      vivo microcomputed tomography at 2, 4, and 6 weeks and further by histologic or
      histomorphometric analysis at 6 weeks postoperation. RESULTS: Mechanical
      stimulation with BMP2 treatment significantly enhanced mineralized tissue volume
      and mineral content at 2 weeks. Histological analysis demonstrated a
      significantly greater area of fibrous connective tissue including bone marrow in
      the stimulated group, suggesting reconstitution of the endosteal canal and more
      advanced bone remodeling present in the mechanical loaded group. Both groups
      receiving BMP2 underwent massive bone formation, achieving bony bridging after
      only 2 weeks, while both control groups, receiving solvent only, revealed a
      persisting nonunion, filled with fibrous connective tissue, prolapsed muscle
      tissue, and a sealed medullary canal at week 6. CONCLUSION: Mechanical loading
      further enhanced the efficacy of BMP2 application evidenced by increased
      mineralized tissue volume and mineralization at the stage of bony callus
      bridging. These data suggest that already a minimal amount of mechanical
      stimulation through load bearing or exercise may be a promising adjunct stimulus
      to enhance the efficacy of cytokine treatment in segmental defects. Further
      studies are required to elucidate the mechanistic interplay between mechanical
      and biological stimuli.

PMID- 22861356
TI  - Hematological manifestations of celiac disease.
AB  - Celiac disease, an autoimmune disease once thought to be uncommon, is now being
      increasingly identified. Our improved diagnostic modalities have allowed us to
      diagnose more and more patients with atypical symptoms who improve on gluten-free
      diet (GFD). We discuss here the latest findings regarding the various
      hematological manifestations of celiac disease and their management. Anemia
      remains the most common hematological manifestation of celiac disease due to many
      mechanisms, and can be the sole presenting symptom. Other manifestations include
      thrombocytosis and thrombocythemia, leukopenia, thromboembolism, increased
      bleeding tendency, IgA deficiency, splenic dysfunction, and lymphoma. The
      diagnosis of celiac disease should always be kept in mind when a patient presents
      with unexplained and isolated hematological finding. Once diagnosed, patients
      should adhere to GFD and be educated about the potential complications of this
      disease. We herein present an algorithm for adequate management and follow-up.

PMID- 22861357
TI  - A new HLA-C*07:244 allele identified by sequence-based typing in a Korean
      individual.
AB  - The C*07:244 changes single nucleotide of C*07:02:01 at codon 75 (CGA -> CAA),
      Arg to Gln.

PMID- 22861358
TI  - Developments in rabies vaccines.
AB  - The development of vaccines that prevent rabies has a long and distinguished
      history, with the earliest preceding modern understanding of viruses and the
      mechanisms of immune protection against disease. The correct application of
      inactivated tissue culture-derived vaccines is highly effective at preventing the
      development of rabies, and very few failures are recorded. Furthermore, oral and
      parenteral vaccination is possible for wildlife, companion animals and livestock,
      again using inactivated tissue culture-derived virus. However, rabies remains
      endemic in many regions of the world and causes thousands of human deaths
      annually. There also remain no means of prophylaxis for rabies once the virus
      enters the central nervous system (CNS). One reason for this is the poor immune
      response within the CNS to infection with rabies virus (RABV). New approaches to
      vaccination using modified rabies viruses that express components of the innate
      immune system are being applied to this problem. Preliminary reports suggest that
      direct inoculation of such viruses could trigger an effective anti-viral response
      and prevent a fatal outcome from RABV infection.

PMID- 22861359
TI  - Lymph node dissection--understanding the immunological function of lymph nodes.
AB  - Lymph nodes (LN) are one of the important sites in the body where immune
      responses to pathogenic antigens are initiated. This immunological function
      induced by cells within the LN is an extensive area of research. To clarify the
      general function of LN, to identify cell populations within the lymphatic system
      and to describe the regeneration of the lymph vessels, the experimental surgical
      technique of LN dissection has been established in various animal models. In this
      review different research areas in which LN dissection is used as an experimental
      tool will be highlighted. These include regeneration studies, immunological
      analysis and studies with clinical questions. LN were dissected in order to
      analyse the different cell subsets of the incoming lymph in detail. Furthermore,
      LN were identified as the place where the induction of an antigen-specific
      response occurs and, more significantly, where this immune response is regulated.
      During bacterial infection LN, as a filter of the lymph system, play a life
      saving role. In addition, LN are essential for the induction of tolerance against
      harmless antigens, because tolerance could not be induced in LN-resected animals.
      Thus, the technique of LN dissection is an excellent and simple method to
      identify the important role of LN in immune responses, tolerance and infection.

PMID- 22861360
TI  - Is interferon-gamma the right marker for bacille Calmette-Guerin-induced immune
      protection? The missing link in our understanding of tuberculosis immunology.
AB  - Bacille Calmette-Guerin (BCG), developed a century ago, is the only licensed
      tuberculosis (TB) vaccine in use to date. The protective efficacy of BCG against
      TB varies with no apparent protection in some population, and mechanisms of its
      immune protection is poorly known, and yet BCG is the most widely used vaccine,
      with more than 4 billion BCG-vaccinated children globally. BCG is probably the
      only licensed vaccine currently in use believed to mediate immune protection
      through the production of interferon (IFN)-gamma by CD4 T cells, which in turn
      activates macrophages to kill Mycobacterium tuberculosis (Mtb). Currently, a
      number of new TB candidate vaccines are in different phases of clinical trial.
      The majority of these new vaccines are either recombinant forms of BCG or prime
      boosters of BCG (rBCG) and their immunogenicity is tested using BCG as a
      benchmark by measuring specific IFN-gamma produced by CD4(+)  T cells as a
      protective immune marker. However, some recent studies that examined mechanisms
      of immune protection of BCG in animals and humans have reported a lack of
      correlation between IFN-gamma production by CD4 cells and BCG-induced immune
      protection. These studies point to the fact that there is a missing link in our
      understanding of TB immunology. Conversely, there is emerging evidence that other
      T cell subsets (gammadelta, gammadelta), CD8(+)  T cells and natural killer (NK)
      cells may play a vital role in immune protection against Mtb infection and BCG
      induced immune protection. gammadelta T cells and NK cells, which were considered
      to be part of the innate immunity in the past, have been shown to develop
      immunological memory upon re-encounter with the same pathogen. In this paper, the
      controversy over the role of IFN-gamma as a marker for protective immunity
      against TB, and emerging data on the role of gammadelta T cells, CD8(+)  and NK
      cells in TB immunology, will be presented.

PMID- 22861361
TI  - How anti-neutrophil cytoplasmic autoantibodies activate neutrophils.
AB  - Neutrophils are pivotal to host defence during infectious diseases. However,
      activated neutrophils may also cause undesired tissue damage. Ample examples
      include small-vessel inflammatory diseases (vasculitis) that are associated with
      anti-neutrophil cytoplasmic autoantibodies (ANCA) residing in the patients'
      plasma. In addition to being an important diagnostic tool, convincing evidence
      shows that ANCA are pathogenic. ANCA-neutrophil interactions induce important
      cellular responses that result in highly inflammatory necrotizing vascular
      damage. The interaction begins with ANCA binding to their target antigens on
      primed neutrophils, proceeds by recruiting transmembrane molecules to initiate
      intracellular signal transduction and culminates in activation of effector
      functions that ultimately mediate the tissue damage.

PMID- 22861362
TI  - Animal models of anti-neutrophil cytoplasmic antibody-associated vasculitis.
AB  - Antibodies against neutrophil proteins myeloperoxidase (MPO) and proteinase 3 are
      thought to cause disease in anti-neutrophil cytoplasmic antibody (ANCA)
      vasculitis. There have been a number of recent developments in the animal models
      of ANCA vasculitis in both mice and rats. These include models based on an immune
      response to MPO generated in MPO-deficient mice, with other models using MPO
      sufficient mice and rats. In addition, there is a report of the use of humanized
      mice where immunodeficient mice have been engrafted with human haematopoietic
      stem cells and injected with patient ANCA. Antibodies to another protein
      lysosomal-associated protein-2 have been found in patients with ANCA vasculitis,
      and evidence from a rat model suggests that they are also pathogenic. These
      models all have advantages and disadvantages, which are discussed. We also
      consider what these models have taught us about the pathogenesis of ANCA
      vasculitis. Experiments using genetically modified mice and pharmacological
      inhibition have given insights into disease mechanisms and have identified
      potential therapeutic targets. Toll-like receptor stimulation modifies disease by
      acting both at the level of tissue injury and in the generation of the autoimmune
      response. Complement is also potentially important with data to support the role
      of the alternative pathway and C5a in particular. Intracellular pathways have
      been examined, with a role showing p38 mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase gamma. Serine proteases are now known to contribute
      to disease by release of interleukin-1beta in ANCA-activated neutrophils and
      monocytes. Other potential therapies studied in these models include the use of
      bortezemib and strategies to modify antibody glycosylation.

PMID- 22861363
TI  - Down syndrome, autoimmunity and T regulatory cells.
AB  - Autoimmune diseases are more represented in Down syndrome (DS) individuals
      compared to chromosomally normal people. Natural T regulatory cells (nT(reg) )
      have been considered to be primary in the role of controlling the intensity and
      targets of the immune response. We have investigated the phenotypical and
      functional alteration of nT(reg) in a group of DS people. The phenotypical
      characteristic of T(reg) cells of 29 DS was analysed and compared with an age
      matched healthy control group. The inhibitory potential of CD4(+) CD25(high)
      CD127(low) T regulatory cells was evaluated on autologous CD4(+) CD25(-) T cell
      proliferation in response to activation with a mytogenic pan-stimulus (anti-CD2,
      anti-CD3 and anti-CD28 antibodies). The CD4(+) CD25(high) cells in the DS and
      control groups were 2.692+/-0.3808%, n=29 and 1.246+/-0.119, n=29%, respectively
      (P=0.0007), with a percentage of forkhead box protein 3 (FoxP3)-expressing cells
      of 79.21+/-3.376%, n=29 and 59.75+/-4.496%, respectively (P=0.0015). CD4(+)
      CD25(+) FoxP3(+) cells were increased in peripheral blood from DS subjects (DS
      mean 5.231+/-0.6065% n=29, control mean 3.076+/-0.3140% n=29). The majority of
      CD4(+) CD25(high) were CD127(low) and expressed a high percentage of FoxP3
      (natural T(reg) phenotype). While the proliferative capacity of DS T cells was
      not altered significantly compared to normal individuals, a reduced inhibitory
      potential of T(reg) compared to healthy controls was clearly observed (mean
      healthy control inhibition in T(eff)  : T(reg) 1:1 co-culture: 58.9%+/-4.157%,
      n=10 versus mean DS inhibition in T(eff) :T(reg) 1:1 co-culture: 39.8+/-4.788%,
      n=10, P=0.0075; mean healthy control inhibition in T(eff)  : T(reg) 1:0.5 co
      culture: 45.10+/-5.858%, n=10 versus DS inhibition in T(eff) : T(reg) 1:0.5 co
      culture: 24.10+/-5.517%, n=10, P=0.0177). DS people present an over-expressed
      peripheral nT(reg) population with a defective inhibitory activity that may
      partially explain the increased frequency of autoimmune disease.

PMID- 22861364
TI  - The immunobiology of apotransferrin in type 1 diabetes.
AB  - The transferrin (Tf) family of iron binding proteins includes important
      endogenous modulators of the immune function that may modulate autoimmune
      diseases. To define more clearly the role of apotransferrin (apoTf) in type 1
      diabetes we determined the impact of this protein on type 1 diabetes as
      investigated in islet cells, animal models and patient sera. First, we
      demonstrated that recombinant apoTf counteracts the cytokine-induced death of
      murine pancreatic islet cells. Secondly, human apoTf administration favourably
      influences the course of type 1 diabetes in animal models, resulting in
      protection against disease development that was associated with reduction of
      insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed
      that patients with newly diagnosed type 1 diabetes manifest significantly lower
      apoTf serum levels compared to healthy controls and patients with long-lasting
      disease. In conclusion, our data suggest the apoTf pivotal role in the
      perpetuation of type 1 diabetes pathology.

PMID- 22861365
TI  - X chromosome gene methylation in peripheral lymphocytes from monozygotic twins
      discordant for scleroderma.
AB  - Scleroderma (SSc) is a rare connective tissue disease characterized by fibrosis,
      microvasculopathy and autoimmune features. The role of genetics is limited in
      SSc, as suggested by similar concordance rates in monozygotic and dizygotic twin
      pairs, while environmental factors may act through epigenetic changes, as
      demonstrated for specific genes. Further, sex chromosome changes have been
      reported in SSc and may explain the female preponderance. In the present study we
      compared the methylation profile of all X chromosome genes in peripheral blood
      mononuclear cells from monozygotic twins discordant (n=7) and concordant (n=1)
      for SSc. Methylated DNA immunoprecipitations from each discordant twin pair were
      hybridized to a custom-designed array included 998 sites encompassing promoters
      of all X chromosome genes and randomly chosen autosomal genes. Biostatistical
      tools identified sites with an elevated probability to be consistently
      hypermethylated (n=18) or hypomethylated (n=25) in affected twins. Identified
      genes include transcription factors (ARX, HSFX1, ZBED1, ZNF41) and surface
      antigens (IL1RAPL2, PGRMC1), and pathway analysis suggests their involvement in
      cell proliferation (PGK1, SMS, UTP14A, SSR4), apoptosis (MTM1), inflammation
      (ARAF) and oxidative stress (ENOX2). In conclusion, we propose that X chromosome
      genes with different methylation profiles in monozygotic twin pairs may
      constitute candidates for SSc susceptibility.

PMID- 22861366
TI  - Monocyte activation is a feature of common variable immunodeficiency irrespective
      of plasma lipopolysaccharide levels.
AB  - Common variable immunodeficiency disorders (CVID), the most frequent cause of
      symptomatic primary immunodeficiency, are defined by impaired antibody
      production. Notwithstanding, T cell activation and granulomatous manifestations
      represent the main causes of CVID morbidity even in patients receiving
      immunoglobulin (Ig) G replacement therapy. Additionally, gut pathology is a
      frequent feature of CVID. In this study, we investigated monocyte imbalances and
      their possible relationship with increased microbial translocation in CVID
      patients. Monocyte subsets were defined according to CD14 and CD16 expression
      levels and evaluated in terms of human leucocyte antigen D-related (HLA-DR), CD86
      and programmed death-1 molecule ligand 1 (PD-L1) expression by flow cytometry, in
      parallel with the quantification of plasma lipopolysaccharide (LPS) and serum
      levels of soluble CD14 (sCD14), LPS-binding protein (LBP) and anti-LPS
      antibodies. CVID patients (n=31) featured significantly increased levels of serum
      sCD14 and an expansion of CD14(bright) CD16(+) monocytes in direct correlation
      with T cell and B cell activation, the latter illustrated by the frequency of the
      CD21(low) CD38(low) subset. Such alterations were not observed in patients
      lacking B cells due to congenital agammaglobulinaemia (n=4). Moreover, we found
      no significant increase in circulating LPS or LBP levels in CVID patients,
      together with a relative preservation of serum anti-LPS antibodies, in agreement
      with their presence in commercial IgG preparations. In conclusion, CVID was
      associated with monocyte imbalances that correlated directly with T cell
      activation markers and with B cell imbalances, without an association with plasma
      LPS levels. The heightened monocyte activated state observed in CVID may
      represent an important target for complementary therapeutic strategies.

PMID- 22861367
TI  - Effects of Leishmania major clones showing different levels of virulence on
      infectivity, differentiation and maturation of human dendritic cells.
AB  - Leishmania parasites and dendritic cell interactions (DCs) play an essential role
      in initiating and directing T cell responses and influence disease evolution.
      These interactions may vary depending on Leishmania species and strains. To
      evaluate the correlation between Leishmania major (Lm) virulence and in-vitro
      human DC response, we compared the ability of high (HV) and low virulent (LV) Lm
      clones to invade, modulate cytokine production and interfere with differentiation
      of DCs. Clones derived from HV and LV (HVDeltalmpdi and LVDeltalmpdi), and
      deleted for the gene coding for a Lm protein disulphide isomerase (LmPDI),
      probably involved in parasite natural pathogenicity, were also used. Unlike LV,
      which fails to invade DCs in half the donors, HV promastigotes were associated
      with a significant increase of the infected cells percentage and parasite burden.
      A significant decrease of both parameters was observed in HVDeltalmpdi-infected
      DCs, compared to wild-type cells. Whatever Lm virulence, DC differentiation was
      accompanied by a significant decrease in CD1a expression. Lm clones decreased
      interleukin (IL)-12p70 production similarly during lipopolysaccharide (LPS)
      induced maturation of DCs. LPS stimulation was associated with a weak increase in
      tumour necrosis factor (TNF)-alpha and IL-10 productions in HV-, HVDeltalmpdi-
      and LVDeltalmpdi-infected DCs. These results indicate that there is a significant
      variability in the capacity of Lm clones to infect human DCs which depends upon
      their virulence, probably involving LmPDI protein. However, independently of
      their virulence, Lm clones were able to down-regulate CD1a expression during DC
      differentiation and IL-12p70 production during DC maturation, which may favour
      their survival.

PMID- 22861368
TI  - Functional deficits of pertussis-specific CD4+ T cells in infants compared to
      adults following DTaP vaccination.
AB  - Understanding the immune responses that explain why infants require multiple
      doses of pertussis vaccine to achieve protection against infection is a high
      priority. The objective of this study was to compare the function and phenotypes
      of antigen-specific CD4(+) T cells in adults (n=12), compared to infants (n=20),
      following vaccination with acellular pertussis (DTaP) vaccine. Peripheral blood
      mononuclear cells (PBMCs) were stimulated with pertussis toxoid (PT), pertactin
      (PRN) and filamentous haemagglutinin (FHA). Multi-parameter flow cytometry was
      used to delineate CD4(+) T cell populations and phenotypes producing interferon
      (IFN)-gamma, interleukin (IL)-2, tumour necrosis factor (TNF)-alpha and IL-4.
      Based on surface CD69 expression, infants demonstrated activation of vaccine
      antigen-specific CD4(+) T cells similar to adults. However, among infants,
      Boolean combinations of gates suggested that type 1 (Th-1) CD4(+) T cell
      responses were confined largely to TNF-alpha(+) IL-2(+) IFN-gamma(-) or TNF
      alpha(+) IL-2(-) IFN-gamma(-) . A significantly lower percentage of
      polyfunctional T helper type 1 (Th1) responses (TNF-alpha(+) IFN-gamma(+) IL-2(+)
      ) and type 2 (Th2) responses (IL-4) were present in the infants compared to
      adults. Moreover, a significantly higher percentage of infants' functional CD4(+)
      T cells were restricted to CD45RA(-) CCR7(+) CD27(+) phenotype, consistent with
      early-stage differentiated pertussis-specific memory CD4(+) T cells. We show for
      the first time that DTaP vaccination-induced CD4(+) T cells in infants are
      functionally and phenotypically dissimilar from those of adults.

PMID- 22861369
TI  - Rapid T cell repopulation after rabbit anti-thymocyte globulin (rATG) treatment
      is driven mainly by cytomegalovirus.
AB  - Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia.
      CD4(+)  T cells remain depleted for up to 2 years, whereas the CD8(+)  T cell
      compartment is refilled rapidly by highly differentiated CD27(-) CD45RA(+)
      CD57(+) effector-type cells. Because the presence of these highly differentiated
      CD8(+)  T cells has been associated with cytomegalovirus (CMV) infection, we
      questioned to what extent restoration of CMV T cell immunity contributes to the
      re-emergence of T cells following rATG treatment. We compared T cell repopulation
      in six CMV-seropositive patients with CMV reactivation (reactivating CMV(+) ) to
      that in three CMV(+)  patients without reactivation (non-reactivating CMV(+) ),
      and to that in three CMV-seronegative recipients receiving a kidney from a CMV
      seronegative donor (CMV(-/-) ). All patients received rATG because of acute
      allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus
      specific CD8(+)  T cells were determined. In reactivating CMV(+)  patients, total
      CD8(+)  T cells reappeared rapidly, whereas in non-reactivating CMV(+)  patients
      they lagged behind. In CMV(-/-)  patients, CD8(+)  T cell counts had not yet
      reached pretransplant levels after 2 years. CMV reactivation was indeed followed
      by a progressive accumulation of CMV-specific CD8(+)  T cells. During
      lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were
      elevated. Although this was most prominent in the CMV-seronegative patients, it
      did not result in an advantage in T cell repopulation in these patients.
      Repopulated CD8(+)  T cells showed increased skewing in their Vbeta repertoire in
      both CMV(-/-)  and reactivating CMV-seropositive patients. We conclude that rapid
      T cell repopulation following rATG treatment is driven mainly by CMV.

PMID- 22861370
TI  - Hepatic expression of CCL2 in alcoholic liver disease is associated with disease
      severity and neutrophil infiltrates.
AB  - Serum levels and liver expression of CCL2 are increased in patients with
      alcoholic hepatitis (AH). In an experimental model of alcoholic liver disease
      (ALD), CCL2 was implicated in proinflammatory cytokines activation and hepatic
      lipid metabolism, but its role in human disease is currently unknown. In a large
      cohort of ALD patients, we analysed plasma levels and liver expression of CCL2
      and their association with liver disease severity and histological lesions. We
      also studied the relationship between -2518 A > G CCL2 and CCR2 190 A/G
      polymorphisms and severity of ALD. We show that CCL2 plasma levels are increased
      in ALD patients compared with healthy subjects. AH patients had significantly
      higher plasma levels and hepatic expression of CCL2 than patients without AH.
      Plasma levels and hepatic expression of CCL2 were associated with disease
      severity. CCL2 liver expression was correlated with neutrophil infiltrate and
      interleukin (IL)-8 expression, but not with steatosis. Moreover, there were more
      G-allele carriers of -2518 A > G CCL2 polymorphism in severe AH patients than in
      other ALD patients. Our results demonstrate that CCL2 is increased in ALD,
      particularly in severe forms, and suggest a role for CCL2 in the pathogenesis of
      ALD via neutrophil recruitment.

PMID- 22861371
TI  - Experimentally induced psoriatic lesion associates with interleukin (IL)-6 in
      mast cells and appearance of dermal cells expressing IL-33 and IL-6 receptor.
AB  - Mast cells are involved in the development of psoriatic lesion, but it is not
      known how mast cells are activated or whether mast cell cytokines are expressed
      during the lesion development. In this study, the Kobner reaction was induced in
      uninvolved psoriatic skin of 18 patients using the tape-stripping technique, and
      a sequence of biopsies was collected at 0 days, 2 h and 3 days or at 0 days, 1
      day and 7 days for histochemical analysis. Eight patients developed the Kobner
      reaction verified at the follow-up visit 2-2.5 weeks later. No significant
      differences were observed in total tryptase(+)  mast cells, psoriasis area and
      severity index and age/sex. Instead, the percentage of tryptase(+)  mast cells
      showing interleukin (IL)-6 immunoreactivity was significantly higher in biopsies
      from Kobner-positive patients than in those from Kobner-negative patients. IL-33
      is a known inducer of IL-6 in mast cells, and the number of IL-33(+)  cells
      increased significantly in Kobner-positive dermal skin at days 3-7. The number of
      dermal cells with IL-6 receptor (IL-6R, CD126) also increased in Kobner-positive
      skin at days 3-7. Unexpectedly, the number of IL-6R(+)  cells was even higher in
      Kobner-negative skin at days 3-7. In the chronic plaque of 10 other psoriatic
      patients, the numbers of IL-6(+)  mast cells and dermal cells showing IL-6R were
      higher than those in the non-lesional skin. In conclusion, the positive Kobner
      reaction is associated with IL-6 in mast cells and appearance of IL-6R(+)  and IL
      33(+)  dermal cells. This suggests that a previously unrecognized vicious circle
      may develop in the early psoriatic lesion.

PMID- 22861372
TI  - Anti-interleukin-12/23p40 antibody attenuates chronic rejection of cardiac
      allografts partly via inhibition gammadeltaT cells.
AB  - In our previous study, we showed that treatment with an anti-interleukin (IL)
      12/23p40 antibody inhibits acute cardiac allograft rejection via inhibiting
      production of interferon (IFN)-gamma and IL-17a. However, the impact of this
      antagonistic anti-p40 antibody on chronic cardiac rejection was unclear. Hearts
      of B6.C-H2bm12/KhEg mice were transplanted into major histocompatibility complex
      (MHC) class II-mismatched C57Bl/6J mice (wild-type, gammadeltaTCR (-/-)  and IL
      17(-/-) ), which is an established murine model of chronic allograft rejection
      without immunosuppression. The mice were treated with control immunoglobulin
      (Ig)G or 200 ug anti-p40 monoclonal antibody on post-operative days,
      respectively. Abdominal palpation and echocardiography were used to monitor graft
      survival. The mice administered with anti-p40 antibody showed a significant
      promotion in graft survival (median survival time >100 days), and histological
      analyses revealed that cardiac allograft rejection was attenuated. Quantitative
      real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analyses
      demonstrated that anti-p40 antibody down-regulated the level of ingraft cytokine
      and chemokine expression (IL-6, IFN-gamma, IL-17a, CCL2 and CCL20). Flow
      cytometry analyses showed that gammadelta T cells are an important ingraft source
      of IFN-gamma and IL-17a and inhibit the production of inflammation cytokine by
      anti-p40 antibody. Compared with the wild-type group, the graft survival time in
      the gammadelta T cell receptor(-/-)  and IL-17(-/-)  mice was prolonged
      significantly. Therefore we propose that, in the chronic allograft rejection
      model, treatment with anti-p40 antibody prolongs graft survival possibly by
      reducing the amount of reactive inflammatory cells, especially gammadelta T
      cells.

PMID- 22861373
TI  - Amelioration of renal damage by administration of anti-thymocyte globulin to
      potential donors in a brain death rat model.
AB  - Brain death (BD), a non-immunological factor of renal injury, triggers an
      inflammatory process causing pathological signs of cell death in the kidney, such
      as necrosis and apoptosis. Kidneys from brain dead donors show lower success
      rates than kidneys from living donors and one strategy to improve transplantation
      outcome is to precondition the donors. For the first time, anti-rat thymoglobulin
      (rATG) was administered in an experimental brain death animal model to evaluate
      if it could ameliorate histopathological damage and improve organ function.
      Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain
      death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h,
      rATG was administered during brain death (10mg/kg). We observed lower creatinine
      levels in treatment groups (means): V, 0.88+/-0.22 mg/dl; BD, 1.37+/-0.07 mg/dl;
      and BD+rATG, 0.64+/-0.02 mg/dl (BD versus BD+rATG, P<0.001). In the BD group
      there appeared to be a marked increase of ATN, whereas ATN was decreased
      significantly in the rATG group (V, 2.25+/-0.5 versus BD, 4.75+/-0.5, P<0.01;
      BD+rATG, 2.75+/-0.5 versus BD 4.75+/-0.5 P<0.01). Gene expression was evaluated
      with reverse transcription-polymerase chain reaction; tumour necrosis factor
      (TNF)-alpha, interleukin (IL)-6, C3, CD86 showed no significant difference
      between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD
      (both cases P<0.01). Myeloperoxidase was increased significantly after the brain
      death setting (V: 32+/-7.5 versus BD: 129+/-18). Findings suggest that rATG
      administered to potential donors may ameliorate renal damage caused by BD. These
      findings could contribute in the search for specific cytoprotective interventions
      to improve the quality and viability of transplanted organs.

PMID- 22861375
TI  - Recognition and reactivity in the binding between Raf kinase inhibitor protein
      and its small-molecule inhibitor locostatin.
AB  - The present work is aimed to provide detail on the binding process between Raf
      kinase inhibitor protein (RKIP) and locostatin, the only exogenous compound known
      to alter the function of RKIP. Understanding the basis of RKIP inhibition for use
      in pharmacological applications is of considerable interest, as dysregulated RKIP
      expression has the potential to contribute to pathophysiological processes.
      Herein, we report a series of atomistic models to describe the protein-ligand
      recognition step and the subsequent reactivity steps. Modeling approaches include
      ligand docking, molecular dynamics, and quantum mechanics/molecular mechanics
      calculations. We expect that such a computational assay will serve to study
      similar complexes in which potency is associated with recognition and reactivity.
      Although previous data suggested a single amino acid residue (His86) to be
      involved in the binding of locostatin, the actual ligand conformation and the
      steps involved in the reactivity process remain elusive from a detailed atomistic
      description. We show that the first reaction step, consisting of a nucleophilic
      attack of the nitrogen (Nepsilon) of His86 at the sp(2)-hybridized carbon (C2) of
      locostatin, presents a late transition state (almost identical to the product).
      The reaction is followed by a hydrogen abstraction and hydrolysis. The
      theoretically predicted overall rate constant (6 M(-1) s(-1)) is in a very good
      agreement with the experimentally determined rate constant (13 M(-1) s(-1)). 

PMID- 22861374
TI  - Safety and tolerability of  pazopanib  in the treatment of renal cell carcinoma.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) is still a challenging disease. Over the
      last 6 years, the use of novel targeted therapies interfering with
      vascularization and inhibition of other downstream pathways has revolutionized
      the therapy of this disease, leading to an improvement of patient outcomes. In
      particular, dysregulation of the vascular endothelial growth factor (VEGF)
      pathway and VEGF protein overexpression have proved important, as they result in
      increased tumor angiogenesis and RCC growth and development. AREAS COVERED: This
      review briefly discusses the mechanisms of action and clinical applications of
      pazopanib . It mainly outlines the safety and tolerability of pazopanib for
      locally advanced/metastatic RCC. Phase III pazopanib safety data are also
      indirectly compared with other standard, antiangiogenic receptor tyrosine kinase
      inhibitors currently used in the management of RCC. EXPERT OPINION: Pazopanib is
      a new drug available in the oncology portfolio to treat patients with
      predominantly clear-cell RCC. The toxicity profile of pazopanib is comparable,
      but in some ways distinct, from other antiangiogenic drugs used in the treatment
      of RCC. Long-term data about late side effects of this treatment are awaited.

PMID- 22861376
TI  - Structures of apo and product-bound human L-asparaginase: insights into the
      mechanism of autoproteolysis and substrate hydrolysis.
AB  - Asparaginases catalyze the hydrolysis of the amino acid asparagine to aspartate
      and ammonia. Bacterial asparaginases are used in cancer chemotherapy to deplete
      asparagine from the blood, because several hematological malignancies depend on
      extracellular asparagine for growth. To avoid the immune response against the
      bacterial enzymes, it would be beneficial to replace them with human
      asparaginases. However, unlike the bacterial asparaginases, the human enzymes
      have a millimolar K(m) value for asparagine, making them inefficient in depleting
      the amino acid from blood. To facilitate the development of human variants
      suitable for therapeutic use, we determined the structure of human l-asparaginase
      (hASNase3). This asparaginase is an N-terminal nucleophile (Ntn) family member
      that requires autocleavage between Gly167 and Thr168 to become catalytically
      competent. For most Ntn hydrolases, this autoproteolytic activation occurs
      efficiently. In contrast, hASNas3 is relatively stable in its uncleaved state,
      and this allowed us to observe the structure of the enzyme prior to cleavage. To
      determine the structure of the cleaved state, we exploited our discovery that the
      free amino acid glycine promotes complete cleavage of hASNase3. Both enzyme
      states were elucidated in the absence and presence of the product aspartate.
      Together, these structures provide insight into the conformational changes
      required for cleavage and the precise enzyme-substrate interactions. The new
      understanding of hASNase3 will serve to guide the design of variants that possess
      a decreased K(m) value for asparagine, making the human enzyme a suitable
      replacement for the bacterial asparaginases in cancer therapy.

PMID- 22861377
TI  - Comparative proteomics of the recently and recurrently formed natural
      allopolyploid Tragopogon mirus (Asteraceae) and its parents.
AB  - * We examined the proteomes of the recently formed natural allopolyploid
      Tragopogon mirus and its diploid parents (T. dubius, T. porrifolius), as well as
      a diploid F(1) hybrid and synthetic T. mirus. * Analyses using iTRAQ LC-MS/MS
      technology identified 476 proteins produced by all three species. Of these, 408
      proteins showed quantitative additivity of the two parental profiles in T. mirus
      (both natural and synthetic); 68 proteins were quantitatively differentially
      expressed. * Comparison of F(1) hybrid, and synthetic and natural polyploid T.
      mirus with the parental diploid species revealed 32 protein expression changes
      associated with hybridization, 22 with genome doubling and 14 that had occurred
      since the origin of T. mirus c. 80 yr ago. We found six proteins with novel
      expression; this phenomenon appears to start in the F(1) hybrid and results from
      post-translational modifications. * Our results indicate that the impact of
      hybridization on the proteome is more important than is polyploidization.
      Furthermore, two cases of homeolog-specific expression in T. mirus suggest that
      silencing in T. mirus was not associated with hybridization itself, but occurred
      subsequent to both hybridization and polyploidization. This study has shown the
      utility of proteomics in the analysis of the evolutionary consequences of
      polyploidy.

PMID- 22861378
TI  - Assembly of three-dimensional hetero-epitaxial ZnO/ZnS core/shell nanorod and
      single crystalline hollow ZnS nanotube arrays.
AB  - Hetero-epitaxial growth along three-dimensional (3D) interfaces from materials
      with an intrinsic large lattice mismatch is a key challenge today. In this work
      we report, for the first time, the controlled synthesis of vertically aligned
      ZnO/ZnS core/shell nanorod arrays composed of single crystalline wurtzite (WZ)
      ZnS conformally grown on ZnO rods along 3D interfaces through a simple two-step
      thermal evaporation method. Structural characterization reveals a "(01
      10)(ZnO)//(01-10)(ZnS) and [0001](ZnO)//[0001](ZnS)" epitaxial relationship
      between the ZnO core and the ZnS shell. It is exciting that arrays of single
      crystalline hollow ZnS nanotubes are also innovatively obtained by simply etching
      away the inner ZnO cores. On the basis of systematic structural analysis, a
      rational growth mechanism for the formation of hetero-epitaxial core/shell
      nanorods is proposed. Optical properties are also investigated via
      cathodoluminescence and photoluminescence measurements. Remarkably, the
      synthesized ZnO/ZnS core/shell heterostructures exhibit a greatly reduced
      ultraviolet emission and dramatically enhanced green emission compared to the
      pure ZnO nanorods. The present single-crystalline heterostructure and hollow
      nanotube arrays are envisaged to be highly promising for applications in novel
      nanoscale optoelectronic devices, such as UV-A photodetectors, lasers, solar
      cells, and nanogenerators.

PMID- 22861379
TI  - Sub-optimal inhibition of thrombus formation ex vivo by aspirin in patients with
      primary thrombocythaemia.

PMID- 22861381
TI  - Quantum dynamics of H2+ in intense laser fields on time-dependent potential
      energy surfaces.
AB  - We have exploited the fully time-dependent Born-Oppenheimer approximation to
      develop time-dependent potential energy surfaces for the lowest two states of
      H(2)(+) in the presence of intense, time-varying, few-cycle laser fields of 2-8
      fs duration. Quantum dynamics are explored on these field-dressed, time-dependent
      potentials. Our results show that the potential well in the lowest-energy state
      of H(2)(+) (i) collapses as the laser pulse reaches its peak amplitude and (ii)
      regains its form on the trailing edge of the pulse, and (iii) the trapped nuclear
      wavepacket has a higher probability of leaking out from the well in the case of
      longer laser pulses. The carrier envelope phase is found to have negligible
      effect on the nuclear dynamics.

PMID- 22861380
TI  - Pyrethroid resistance in Anopheles gambiae s.s. and Anopheles arabiensis in
      western Kenya: phenotypic, metabolic and target site characterizations of three
      populations.
AB  - Field and laboratory investigations revealed phenotypic, target site and
      metabolic resistance to permethrin in an Anopheles gambiae s.s. (Diptera:
      Culicidae) population in Bungoma District, a region in western Kenya in which
      malaria is endemic and rates of ownership of insecticide-treated bednets are
      high. The sensitivity of individual An. gambiae s.l. females as indicated in
      assays using World Health Organization (WHO) test kits demonstrated reduced
      mortality in response to permethrin, deltamethrin and bendiocarb. Estimated time
      to knock-down of 50% (KDT50 ) of the test population in Centers for Disease
      Control (CDC) bottle bioassays was significantly lengthened for the three
      insecticides compared with that in a susceptible control strain. Anopheles
      arabiensis from all three sites showed higher mortality to all three insecticides
      in the WHO susceptibility assays compared with the CDC bottle assays, in which
      they showed less sensitivity and longer KDT50 than the reference strain for
      permethrin and deltamethrin. Microplate assays revealed elevated activity of beta
      esterases and oxidases, but not glutathione-S-transferase, in An. gambiae s.s.
      survivors exposed to permethrin in bottle bioassays compared with knocked down
      and unexposed individuals. No An. arabiensis showed elevated enzyme activity. The
      1014S kdr allele was fixed in the Bungoma An. gambiae s.s. population and absent
      from An. arabiensis, whereas the 1014F kdr allele was absent from all samples of
      both species. Insecticide resistance could compromise vector control in Bungoma
      and could spread to other areas as coverage with longlasting insecticide-treated
      bednets increases.

PMID- 22861383
TI  - Tunable synthesis of hierarchical mesoporous silica nanoparticles with radial
      wrinkle structure.
AB  - We studied the formation mechanism of hierarchical mesoporous silica
      nanoparticles with a wrinkle structure (wrinkled silica nanoparticles, WSNs), and
      a method for substructure control of silica nanoparticles was proposed. We
      confirmed that WSNs were generated in the bicontinuous microemulsion phase of the
      Winsor III system. By using the phase behavior of the Winsor III system, which
      depends on the water-surfactant-oil mixing ratio, and by adding various
      cosolvents, we could precisely control the structure of silica nanoparticles from
      the mesoporous to the wrinkle form; furthermore, we could control the
      interwrinkle distance.

PMID- 22861382
TI  - Relationship between social support and quality of life in childbearing women
      during the perinatal period.
AB  - OBJECTIVE: To explore demographic and social support predictors of health-related
      quality of life (HRQoL) (mental and physical) for childbearing women in the
      perinatal period. DESIGN: Longitudinal. SAMPLE: Three public hospitals in
      metropolitan Brisbane, Australia. PARTICIPANTS: Four hundred seventy-three (473)
      women recruited at 36 weeks of pregnancy, and 6 and 12 weeks following
      childbirth. METHODS: The Short Form-12 (SF-12) Version 2 Health Survey was used
      to measure the mental and physical domains of HRQoL. Social support was measured
      using the Maternal Social Support Scale (MSSS). RESULTS: Mean scores for the
      mental and physical domains of HRQoL were lower than population norms. Social
      support was found to be a significant and consistent predictor of higher HRQoL
      scores, particularly in the physical domain at 12 weeks following child birth and
      mental domain during the perinatal period. The relationship between social
      support and HRQoL was found to be independent of other factors including
      education, length of relationship with partner, age, parity, and antenatal visit.
      The only other significant predictor was length of relationship with partner in
      the mental domain at 36 weeks of pregnancy. CONCLUSION: Social support is a
      significant and consistent predictor of a mother's HRQoL during the perinatal
      period. Nurses and midwives need to assess social support, rather than making
      assumptions based on demographic factors.

PMID- 22861384
TI  - Geminal alkene-alkyne cross metathesis using a relay strategy.
AB  - A relay strategy was employed to achieve an intermolecular ene-yne metathesis
      between 1,1-disubstituted alkenes and alkynes. The relay serves to activate an
      unreactive alkene which will not participate in ene-yne metathesis. The new relay
      cross ene-yne metathesis gives rise to 1,1,3-trisubstituted-1,3-dienes previously
      inaccessible by direct ene-yne metathesis methods.

PMID- 22861386
TI  - Serum and CSF soluble CD26 and CD30 concentrations in healthy pediatric surgical
      outpatients.
AB  - Activated T-helper type 1 (Th1) lymphocytes induce a cellular type immune
      response, and Th2 lymphocytes, a humoral or antibody-mediated type immune
      response. Soluble CD26 (sCD26) and soluble CD30 (sCD30) are regarded as markers
      of Th1 and Th2 lymphocyte activation, respectively. Serum from 112 generally
      healthy pediatric surgical patients and cerebrospinal fluid (CSF) from 39, aged 1
      17 years were measured for sCD26 and sCD30 using an enzyme-linked immunosorbent
      assay method. The detection limit for sCD26 was 6.8 ng/ml and for sCD30, 1.9
      IU/ml. For serum sCD26 and sCD30, 2.5% and 97.5% percentiles constituted the
      reference limits, and the 95% credible intervals for the percentiles were
      calculated using regression models with a Bayesian approach. A significant
      between-gender difference was observed (P = 0.015) in serum sCD26 concentration,
      of which the lower limits ranged between 273 and 716 ng/ml for girls and 235 and
      797 ng/ml for boys. The upper limits ranged between 1456 and 1898 ng/ml for girls
      and between 1419 and 1981 ng/ml for boys. Moreover, the concentrations of sCD26
      increased in infants and children up to 10 years in girls and 12 years in boys.
      After this however, the values decreased. The serum sCD30 concentration was
      highest among the youngest infants aged 1 year (80-193 IU/ml), after which a
      consistent age-related decrease was found. The lowest values were found at the
      age of 17 years (10-89 IU/ml). A significant between-gender difference in sCD30
      concentration was observed (P = 0.019). sCD26 and sCD30 concentrations were low
      in the CSF samples analyzed: 13.3 ng/ml (median); range 8.3-51.5 ng/ml and 7.6
      IU/ml; 2.1-18.5 IU/ml, respectively. Reference limits for serum sCD26 in children
      aged 1-17 years were established as being 235-1800 ng/ml in toddlers and 400-1800
      ng/ml in female adolescents and 700-2000 ng/ml in male adolescents. For sCD30;
      reference limits of 80-190 IU/ml were established in the youngest age group and
      10-90 IU/ml in adolescents.

PMID- 22861385
TI  - Persistence and remission of musculoskeletal pain in community-dwelling older
      adults: results from the cardiovascular health study.
AB  - OBJECTIVES: To characterize longitudinal patterns of musculoskeletal pain in a
      community sample of older adults over a 6-year period and to identify factors
      associated with persistence of pain. DESIGN: Secondary analysis of the
      Cardiovascular Health Study. SETTING: Community-based cohort drawn from four U.S.
      counties. PARTICIPANTS: Five thousand ninety-three men and women aged 65 and
      older. MEASUREMENTS: Over a 6-year period, pain was assessed each year using a
      single question about the presence of pain in any bones or joints during the last
      year. If affirmative, participants were queried about pain in seven locations
      (hands, shoulders, neck, back, hips, knees, feet). Participants were categorized
      according to the percentage of time that pain was present and according to the
      intermittent or chronic pattern of pain. Factors associated with persistent pain
      during five remaining years of the study were identified. RESULTS: Over 6 years,
      32% of participants reported pain for three or more consecutive years, and 32%
      reported pain intermittently. Of those who reported pain the first year, 54% were
      pain free at least once during the follow-up period. Most of the pain at specific
      body locations was intermittent. Factors associated with remission of pain over 5
      years included older age, male sex, better self-rated health, not being obese,
      taking fewer medications, and having fewer depressive symptoms. Approximately
      half of those with pain reported fewer pain locations the following year.
      CONCLUSION: Musculoskeletal pain in older adults, despite high prevalence, is
      often intermittent. The findings refute the notion that pain is an inevitable,
      unremitting, or progressive consequence of aging.

PMID- 22861387
TI  - Salivary levels of HNP 1-3 are related to oral ulcer activity in Behcet's
      disease.
AB  - BACKGROUND: Saliva contains antimicrobial peptides derived from oral epithelium
      as well as neutrophils in the innate immune response. The aim of this study was
      to examine the association between salivary human neutrophil peptide (HNP) 1-3
      levels originating from neutrophils and oral ulcers in patients with Behcet's
      disease (BD). METHODS: Ninety-five patients with BD (F/M: 39/56; mean age: 38.7
      +/- 11.9 years) and 53 healthy controls (HC; F/M: 23/30; mean age: 35.2 +/- 10.1
      years) were included in the study. The disease control group (F/M: 20/33; mean
      age: 33.7 +/- 10.7 years) was comprised of patients with oral infection regarding
      endodontic infection (n = 32) and pericoronitis (n = 21). Salivary HNP 1-3 levels
      of groups were measured in unstimulated samples by ELISA (Hycult, the
      Netherlands). RESULTS: A statistically significant increase was found in salivary
      HNP 1-3 levels of patients with BD (2268.28 +/- 1216.38 MUg/ml) compared with HC
      (1836.49 +/- 857.76 MUg/ml), patients with endodontic infection (849.9 +/- 376.1
      MUg/ml), and patients with pericoronitis (824.3 +/- 284.02 MUg/ml; P = 0.024,
      0.000 and 0.000, respectively). The ratio of active oral ulcer (100%, n = 14) was
      higher in low HNP 1-3 levels (<= 1000 MUg/ml) than the others (66.7%, n = 54) in
      active patients with BD (P = 0.008). Moreover, salivary HNP 1-3 levels were
      significantly lower in patients with endodontic infection and patients with
      pericoronitis compared with those in the HC group and patients with BD (P =
      0.000). CONCLUSION: A decrease in salivary HNP 1-3 levels might be a biological
      factor for predisposition to oral ulcers in patients with BD and oral infection
      in healthy patients.

PMID- 22861481
TI  - Celebrating twenty years of progress: World Breastfeeding Week 2012.

PMID- 22861482
TI  - Global baby-friendly hospital initiative monitoring data: update and discussion.
AB  - BACKGROUND: The World Health Organization (WHO)/UNICEF Baby-Friendly Hospital
      Initiative (BFHI) was developed to support the implementation of the Ten Steps
      for Successful Breastfeeding. The purpose of this study is to assess trends in
      the numbers facilities ever-designated "baby-friendly," to consider uptake of the
      new WHO/UNICEF BFHI materials, and to consider implications for future
      breastfeeding support. MATERIALS AND METHODS: The national contacts from the 2006
      2007 UNICEF BFHI update were recontacted, as were WHO and UNICEF officers
      worldwide, to ascertain the number of hospitals ever-designated "baby-friendly,"
      presence of a government breastfeeding oversight committee, use of the new BFHI
      materials and, if yes, use of the new maternity or human immunodeficiency virus
      (HIV) materials. RESULTS: Seventy countries reporting in 2010-2011 and the
      updates from an additional 61 reporting in 2006-2007 (n=131, or 66% of the 198
      countries) confirm that there are at least 21,328 ever-designated facilities.
      This is 27.5% of maternities worldwide: 8.5% of those in industrialized countries
      and 31% in less developed settings. In 2010, government committees were reported
      by 18 countries, and 34 reported using the new BFHI materials: 14 reported using
      the maternity care and 11 reported using the HIV materials. CONCLUSIONS: Rates of
      increase in the number of ever-certified "baby-friendly" hospitals vary by region
      and show some chronological correlation with trends in breastfeeding rates.
      Although it is not possible to attribute this increase to the BFHI alone, there
      is ongoing interest in Ten Steps implementation and in BFHI. The continued growth
      may reflect the dedication of ministries of health and national BFHI groups, as
      well as increasing recognition that the Ten Steps are effective quality
      improvement practices that increase breastfeeding and synergize with community
      interventions and other program efforts. With renewed interest in
      maternal/neonatal health, revitalization of support for Ten Steps and their
      effective institutionalization in maternity practices should be considered.
      Future updates are planned to assess ongoing progress and impact, and ongoing
      updates from national committees are welcome.

PMID- 22861483
TI  - Provocative breastfeeding images are counterproductive.

PMID- 22861484
TI  - Quick reference breastfeeding guide available for medical students and residents.

PMID- 22861485
TI  - A spectroscopic approach to the solvation of anesthetics in jets: propofol(H2O)n,
      n = 4-6.
AB  - Propofol is a widely used nonvolatile anesthetic that exerts its action by
      docking to GABAA receptors. The docking process is a competition between
      solvation of the anesthetic by the extracellular medium and the stabilization
      inside the active site, and therefore a deep knowledge of the process requires of
      a good understanding of the solvation process. In this work we create propofol
      water complexes containing up to six water molecules using supersonic expansions.
      We determine their structure by means of a number of mass-resolved laser-based
      excitation spectroscopic techniques, namely two-color REMPI, UV/UV, and IR/UV
      double resonance techniques, combined with computational chemistry. The results
      clearly show that water tends to self-aggregate, interacting with the hydrophilic
      side of propofol. Furthermore, a transition from planar to three-dimensional
      structures is observed in propofol(H2O)6. Comparison with structural data from
      similar systems such as phenol-water and pure water clusters follows. 

PMID- 22861486
TI  - Inhibitory function of the dorsomedial hypothalamic nucleus on the hypothalamic
      pituitary-adrenal axis response to an emotional stressor but not immune
      challenge.
AB  - Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in
      the regulation of autonomic and neuroendocrine stress responses. However,
      although projections from the DMH to the paraventricular hypothalamic nucleus
      (PVN), which is the critical site of the neuroendocrine stress axis, have been
      described, the impact of DMH neurones in the modulation of hypothalamic-pituitary
      adrenal (HPA) axis activation during stress is not fully understood. The present
      study aimed to investigate the role of the DMH in HPA axis responses to different
      types of stimuli. Male Sprague-Dawley rats fitted with a chronic jugular venous
      catheter were exposed to either an emotional stressor (elevated platform
      exposure) or immune challenge (systemic interleukin-1beta administration).
      Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the
      emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone
      levels during and after elevated platform exposure in lesioned animals compared
      to sham-lesioned controls. Moreover, DMH-lesioned animals showed increased
      neuronal activation in the PVN, as indicated by a higher c-Fos expression after
      elevated-platform exposure compared to controls. By contrast, DMH-lesions had no
      effects on HPA axis responses to immune challenge. Taken together, our data
      suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation
      that is dependent upon the nature of the stimulus being important in response to
      an emotional stressor but not to immune challenge.

PMID- 22861487
TI  - Dynamics and visualization of MCF7 adenocarcinoma cell death by aptamer-C1q
      mediated membrane attack.
AB  - This study was designed to characterize binding of a DNA aptamer to breast cancer
      cells and to test whether that aptamer could be used to kill target cells in
      vitro as part of an aptamer-C1q protein conjugate by coupling to the classic
      complement cascade. A biotinylated DNA aptamer designated MUC1-5TR-1 was shown to
      decorate the plasma membranes of human breast adenocarcinoma (MCF7) cells via
      fluorescence confocal microscopy. Biotinylated aptamer binding successfully
      initiated the classical complement pathway leading to complement fixation on the
      target cells via a streptavidin-C1q conjugate as previously reported. Forster
      Resonance Energy Transfer (FRET) measurements demonstrated membrane
      depolarization upon aptamer binding, providing indirect evidence of membrane
      attack complex (MAC) formation as a result of aptamer binding. Transmission
      electron microscopy (TEM) and immunogold labeling confirmed that aptamer-mediated
      complement fixation results in MAC formation on the plasma membrane, leading to
      osmotic swelling and cell death. This approach may provide a much less toxic and
      more precisely targeted "antibody-like" treatment for cancers by coupling to the
      patient's innate immune system in much the same way as more expensive humanized
      monoclonal antibodies.

PMID- 22861488
TI  - Environmental risk assessment for the small tortoiseshell Aglais urticae and a
      stacked Bt-maize with combined resistances against Lepidoptera and Chrysomelidae
      in central European agrarian landscapes.
AB  - The cultivation of Lepidoptera-resistant Bt-maize may affect nontarget
      butterflies. We assessed the risk posed by event MON89034 * MON88017 (expressing
      Cry1A.105 and Cry2Ab2 against corn borers) to nontarget Lepidoptera. Using the
      small tortoiseshell Aglais urticae, a butterfly species common in central Europe,
      as a test organism we (i) assessed the toxicity of Bt-maize pollen on butterfly
      larvae; (ii) measured pollen deposition on leaves of the host plant Urtica
      dioica; (iii) mapped the occurrence and distribution of host plants and larvae in
      two arable landscapes in Germany during maize anthesis; and (iv) described the
      temporal occurrence of a 1-year population of A. urticae. (i) Larvae-fed 200 Bt
      maize pollen grains/cm(2) had a reduced feeding activity. Significant differences
      in developmental time existed at pollen densities of 300 Bt-maize pollen
      grains/cm(2) and in survival at 400 grains/cm(2). (ii) The highest pollen amount
      found was 212 grains/cm(2) at the field margin. Mean densities were much lower.
      (iii) In one region, over 50% of A. urticae nests were located within 5 m of a
      maize field, while in the other, all nests were found in more than 25 m distance
      to a maize field. (iv) The percentage of larvae developing during maize anthesis
      was 19% in the study area. The amount of pollen from maize MON89034 * MON88017
      found on host plants is unlikely to adversely affect a significant proportion of
      larvae of A. urticae. This paper concludes that the risk of event MON89034 *
      MON88017 to populations of this species is negligible.

PMID- 22861489
TI  - Specific His6-tag attachment to metal-functionalized polymersomes relies on
      molecular recognition.
AB  - The development of nanocarriers for drug/protein delivery is in focus today, as
      they can serve to both decrease dosages and improve localization to a desired
      biological compartment. A powerful tool to functionalize these carriers is
      specific affinity tagging supported by molecular recognition, a key principle in
      biology. However, the geometry of the binding region in a molecular recognition
      process, and thus its conformation and specificity, are in many cases poorly
      understood. Here, we demonstrate that short, model peptides, His(6)-tags,
      selectively recognize Cu(II)-trisnitrilotriacetic acid moieties (Cu(II)-trisNTA)
      when exposed at the surfaces of polymer vesicles designed to serve as
      nanocarriers or as surfaces for proteins binding. A mixture of poly(butadiene)-b
      poly(ethylene oxide) (PB-b-PEO) and Cu(II)-trisNTA-functionalized PB-b-PEO
      diblock copolymers (10:1) self-assembles in aqueous solution, generating vesicles
      with a hydrodynamic radius of approximately 100 nm, as established by light
      scattering and TEM. Fluorescently labeled His(6) tags specifically bind to metal
      centers exposed on vesicles' surface, with a dissociation constant of 0.6 +/- 0.2
      MUM, as determined by fluorescence correlation spectroscopy. The significant
      rearrangement in the geometry of the metal center upon peptide binding was
      characterized by a combination of CW-EPR, pulse-EPR, and DFT computations.
      Understanding the binding configuration around the metal center inside NTA pocket
      exposed at the surface of vesicles supports further development of efficient
      targetable nanocarriers that can be recognized selectively by molecular
      recognition in a biological environment and facilitates their immobilization on
      solid supports and their use in two-dimensional protein arrays.

PMID- 22861490
TI  - Does heparin coating reduce encrustation of biliary plastic endoprostheses? A
      prospective randomized trial.
AB  - OBJECTIVE: Common bile duct stenting is widely performed for bridging benign and
      malignant obstructions. A major limitation is early stent occlusion making
      regular stent exchange necessary. Covalent binding of glycosaminoglycanes to
      polyethylene stents proved to reduce encrustation in urological implants. Since
      development of urological and biliary stent occlusion shows parallels, the aim of
      the study was to evaluate the efficacy of heparin coating of biliary
      endoprostheses in preventing encrustation. MATERIAL AND METHODS: In a prospective
      randomized trial, heparin-coated and native stents were endoscopically placed for
      almost 90 days on average. After removal, all stents were dried (50 degrees C, 24
      h), weighed and after longitudinal incision visible encrustation and
      discoloration recorded. Fifty-three patients (21 females/32 males, 70 +/- 12 (42
      87) years) were included; 13 patients (4 females/9 males, 58-79 years) completed
      the study according to the protocol. RESULTS: After removal, mean weight of
      encrustation in native stents was more than double as high as of covered stents
      (native: 37.9 +/- 19.8 (16-93) mg; covered: 17.6 +/- 6.7 (9-33) mg). In 12 of 13
      cases, the encrustation weight of the native stent was higher than that of the
      corresponding covered stent in the same patient. Premature stent explantation
      became necessary in 3 of 13 native stents, because of recurrent jaundice or
      cholangitis but only in 1 of 13 covered stents. After longitudinal incision, the
      three uncovered stents showed excessive encrustation whereas no significant
      encrustation was found in the covered prosthesis. Altogether, covered stents
      showed less visible accumulation of clogging material and discoloration than
      native stents. CONCLUSIONS: Covalent bound heparin is highly effective in
      preventing encrustation of biliary polyethylene endoprostheses.

PMID- 22861491
TI  - Genome resequencing reveals multiscale geographic structure and extensive linkage
      disequilibrium in the forest tree Populus trichocarpa.
AB  - * Plant population genomics informs evolutionary biology, breeding, conservation
      and bioenergy feedstock development. For example, the detection of reliable
      phenotype-genotype associations and molecular signatures of selection requires a
      detailed knowledge about genome-wide patterns of allele frequency variation,
      linkage disequilibrium and recombination. * We resequenced 16 genomes of the
      model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations
      using 29,213 single-nucleotide polymorphisms. * Significant geographic
      differentiation was present at multiple spatial scales, and range-wide
      latitudinal allele frequency gradients were strikingly common across the genome.
      The decay of linkage disequilibrium with physical distance was slower than
      expected from previous studies in Populus, with r(2) dropping below 0.2 within 3
      6 kb. Consistent with this, estimates of recent effective population size from
      linkage disequilibrium (N(e) ~ 4000-6000) were remarkably low relative to the
      large census sizes of P. trichocarpa stands. Fine-scale rates of recombination
      varied widely across the genome, but were largely predictable on the basis of DNA
      sequence and methylation features. * Our results suggest that genetic drift has
      played a significant role in the recent evolutionary history of P. trichocarpa.
      Most importantly, the extensive linkage disequilibrium detected suggests that
      genome-wide association studies and genomic selection in undomesticated
      populations may be more feasible in Populus than previously assumed.

PMID- 22861492
TI  - Newborn clinical outcomes of the AWHONN late preterm infant research-based
      practice project.
AB  - OBJECTIVE: To describe the neonatal health risks (hypothermia, hypoglycemia,
      hyperbilirubinemia, respiratory distress, the need for a septic workup, and
      feeding difficulties) experienced by late preterm infants (LPIs) from a large
      multisite study and determine how these risks were affected by gestational age at
      birth. DESIGN: Descriptive analysis of prospective data obtained as part of the
      AWHONN Late Preterm Infant Research-Based Practice Project. SETTING: Fourteen
      hospitals located through the United States and Canada. PARTICIPANTS: Late
      preterm infants (802) born at gestational ages between 34 0/7 and 36 6/7 weeks.
      METHODS: Nurses at each site obtained consent from the mother of the infant. The
      data about the infant were gathered from the infant's medical record. RESULTS:
      Thirty-six percent of LPIs were initially cared for in a special care nursery;
      approximately one half of these infants were eventually transferred to a well
      baby nursery. Of the 64% of LPIs initially cared for in a routine nursery, 10%
      were transferred to a special care unit or neonatal intensive care unit (NICU).
      More than one half of LPIs experienced hypothermia, hypoglycemia, feeding
      difficulties, hyperbilirubinemia, and respiratory distress and/or needed a septic
      workup. The risk for these problems was higher in infants of younger gestational
      ages. Thirty-two percent of the infants were bathed during the first 2 hours of
      life, and by 4 hours, more than two thirds had had their first bath. Fifty-two
      percent received kangaroo care during the first 48 hours of life. CONCLUSION:
      These findings support those of smaller studies indicating that LPIs are at high
      risk for developing health problems during their neonatal hospitalization. Nurses
      may be able to ameliorate some of these health problems through early
      identification of problems and simple, inexpensive interventions such as avoiding
      early bathing and promoting kangaroo care.

PMID- 22861493
TI  - The contribution of patient interviews to the identification of drug-related
      problems in home medication review.
AB  - WHAT IS KNOWN AND OBJECTIVE: To determine to what extent patient interviews
      contribute to the identification of drug-related problems (DRPs) in home
      medication reviews, in terms of number, type and clinical relevance. METHODS: We
      performed a cross-sectional study within the intervention arm of a randomized
      controlled trial. Patients were recruited from 10 Dutch community pharmacies.
      Patients were eligible if they were home-dwelling, aged 65 years and over and
      used five or more different drugs, including at least one cardiovascular or
      antidiabetic drug. The community pharmacist interviewed the patient at home about
      the medicines and identified potential DRPs in combination with medication and
      clinical records. This medication review was assessed and modified by an
      independent pharmacist reviewers' panel. Outcomes were the number and type of
      DRPs and recommendations and percentage of clinical relevant DRPs. Clinical
      relevance of DRPs was assessed by DRPs assigned a high priority, DRPs followed by
      recommendations for drug change and DRPs followed by implemented recommendations
      for drug change. RESULTS: A total of 1565 potential DRPs and recommendations (10
      per patient).were identified for 155 patients (median age, 76 years; 54% women).
      Fifty-eight per cent of all recommendations involved a drug change; 27% of all
      DRPs were identified during patient interviews and 74% from medication and
      clinical records. Compared to DRPs identified from patient medication and
      clinical records, DRPs identified during patient interviews were more frequently
      assigned a high priority (OR = 1.8 [1.4-2.2]), were more frequently associated
      with recommendations for drug change (OR = 2.4 [1.9-3.1]) and were implemented
      recommendations for drug change (OR = 2.8 [2.1-3.7]). WHAT IS NEW AND CONCLUSION:
      This study shows that more than a quarter of all DRPs were identified during
      patient interviews. DRPs identified during patient interviews were more
      frequently assigned a higher clinical relevance.

PMID- 22861494
TI  - Directed self-assembly of lipid nanotubes from inverted hexagonal structures.
AB  - Conventional lipid-tube formation is based on either a tube phase of certain
      lipids or the shape transformation of lamellar structures by applying a point
      load. In the present study, lipid blocks in inverted hexagonal phase made of 1,2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were shown to protrude lipid
      nanotubes upon a fluid-dynamic flow on polyelectrolyte-functionalized surfaces in
      physiological buffer solution. The outer diameter of the tubes is 19.1 +/- 4.5 nm
      and their lengths are up to several hundred micrometers. The method described
      enables the alignment and patterning of lipid nanotubes into various (including
      curvy) shapes with a microfluidic system.

PMID- 22861495
TI  - Numerical validation of IFT in the analysis of protein-surfactant complexes with
      SAXS and SANS.
AB  - The use of the indirect Fourier transform methods for evaluating structural
      parameters directly in real space with small-angle scattering measurements is
      validated for the analysis of protein-surfactant complexes. An efficient Monte
      Carlo approach rapidly generates in silico structures based on a realistic pearl
      necklace model for denatured proteins decorated with surfactant micelles.
      Corresponding scattering profiles are calculated and averaged over a large number
      of possible configurations for each structure. IFT algorithms are then used to
      calculate the corresponding pair-distance distribution function, and structural
      information is extracted directly without model fitting. The extracted parameters
      are compared and correlated with the known structure of the simulated complexes
      to assess the quality of the information that can be reliably obtained from these
      systems. The average extension, nearest-neighbor micelle distance, and average
      number of associated micelles are all accurately extracted through IFT
      calculations. Improved and simple approaches to reliably extract the average
      extension of the complex and the total number of associated micelles are
      presented.

PMID- 22861496
TI  - Safety and efficacy evaluation of  ambrisentan  in pulmonary hypertension.
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterized by an
      increase in pulmonary vascular resistance, which can lead to right heart failure
      and death. Endothelin-1 binding ETA and ETB receptors seem to play a critical
      role in the pathogenesis and progression of the disease, and oral endothelin
      receptor antagonists (ERAs) have been shown to be an effective treatment.
      Bosentan and ETA-selective ambrisentan are the ERAs currently available for PAH
      treatment. AREAS COVERED: On the basis of the analysis of the literature, this
      paper addresses the efficacy and safety of ambrisentan in the treatment for PAH.
      EXPERT OPINION: Ambrisentan has shown an efficacy comparable with other ERAs.
      Compared with bosentan, ambrisentan seems to have a better safety profile with
      regards to hepatic safety and drug-drug interactions. On the other hand,
      ambrisentan shows a higher rate of other adverse events, such as nasal congestion
      and peripheral edema. Ambrisentan is a viable option for PAH treatment. However,
      there is still a need for more robust data about long-term mortality, treatment
      in non-PAH pulmonary hypertension (PH) (such as PH due to left heart disease and
      PH due to chronic hypoxic lung diseases) and combination therapy.

PMID- 22861497
TI  - A rare case of congenital angiokeratoma of the glans penis treated using a 595-nm
      pulsed dye laser.

PMID- 22861498
TI  - Does Microcystis aeruginosa have quorum sensing?
AB  - Quorum sensing (QS) is a system of cell-to-cell communication by means of
      intercellular signaling molecules to coordinate a set of targeted gene expression
      or repression in many Gram-negative bacteria; it plays important roles for
      bacteria in adaptation to adverse environmental conditions. In this study, we
      first demonstrated that Microcystis aeruginosa PCC-7820 could produce QS-related
      signal acylated homoserine lactones (AHLs) among the metabolite of axenic M.
      aeruginosa, based on bioassay and liquid chromatography-mass spectrometry (LC-MS)
      analysis. The concentration of the AHLs in the culture medium was cell density
      dependent and reached a maximum of 18 nM at 1.03 * 10(7) cells mL(-1), 30 days
      after inoculation. The regulation mechanism of QS in M. aeruginosa and its
      possible role in bloom formation are discussed.

PMID- 22861499
TI  - Novel second-generation di-2-pyridylketone thiosemicarbazones show synergism with
      standard chemotherapeutics and demonstrate potent activity against lung cancer
      xenografts after oral and intravenous administration in vivo.
AB  - We developed a series of second-generation di-2-pyridyl ketone thiosemicarbazone
      (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands to improve the
      efficacy and safety profile of these potential antitumor agents. Two novel DpT
      analogues, Dp4e4mT and DpC, exhibited pronounced and selective activity against
      human lung cancer xenografts in vivo via the intravenous and oral routes.
      Importantly, these analogues did not induce the cardiotoxicity observed at high
      nonoptimal doses of the first-generation DpT analogue, Dp44mT. The Cu(II)
      complexes of these ligands exhibited potent antiproliferative activity having
      redox potentials in a range accessible to biological reductants. The activity of
      the copper complexes of Dp4e4mT and DpC against lung cancer cells was synergistic
      in combination with gemcitabine or cisplatin. It was demonstrated by EPR
      spectroscopy that dimeric copper compounds of the type [CuLCl](2), identified
      crystallographically, dissociate in solution to give monomeric 1:1 Cu:ligand
      complexes. These monomers represent the biologically active form of the complex.

PMID- 22861500
TI  - Effects of differences in organic supply on bacterial diversity subject to viral
      lysis.
AB  - Bacterial diversity is believed to be controlled both by bottom-up and top-down
      mechanisms such as nutrient competition, predation and viral lysis. We
      hypothesise that lytic viruses create trophic niches within bacterial
      communities, and thus primarily control richness and evenness, while substrate
      composition primarily controls community composition, that is, the inhabitants of
      these niches. To investigate this, we studied diversity of mixed bacterial
      communities subject to viruses under different regimes of organic matter supply.
      From a predator-free inoculum, bacterial communities were allowed to develop in
      batch cultures where the organic substrate was either a single compound [glucose
      (G)] or more complex mixtures produced by phytoplankton [Phaeocystis pouchetii
      (P) or Thalassiosira sp. (T)]. Throughout the experiment, c. 98% of the sequences
      in treatment G belonged to the Gammaproteobacteria class, which dominated also in
      the initial phase of the other treatments [T (c. 87%) and P (62%)]. In treatment
      T, the composition shifted to a dominance of Alphaproteobacteria (c. 37%), while
      in P, the proportion of Gammaproteobacteria remained stable. Richness increased
      with increasing substrate complexity, while evenness remained similar in the
      different treatments. The results suggest that both substrate composition (bottom
      up) and viral lysis (top-down) operate simultaneously in the control of bacterial
      diversity. Despite the reduction in factors supposed to influence prokaryote
      diversity, the system was still complex if taken into account the potential
      synergistic interactions within and between the remaining factors.

PMID- 22861501
TI  - Treatment withdrawal and acute brain injury: an integral part of care.

PMID- 22861502
TI  - Mobile phones and the developing world.

PMID- 22861503
TI  - Usability testing of a prototype Phone Oximeter with healthcare providers in high
      and low-medical resource environments.
AB  - To increase the use of pulse oximetry by capitalise on the wide availability of
      mobile phones, we have designed, developed and evaluated a prototype pulse
      oximeter interfaced to a mobile phone. Usability of this Phone Oximeter was
      tested as part of a rapid prototyping process. Phase 1 of the study (20 subjects)
      was performed in Canada. Users performed 23 tasks, while thinking aloud. Time for
      completion of tasks and analysis of user response to a mobile phone usability
      questionnaire were used to evaluate usability. Five interface improvements were
      made to the prototype before evaluation in Phase 2 (15 subjects) in Uganda. The
      lack of previous pulse oximetry experience and mobile phone use increased median
      (IQR [range]) time taken to perform tasks from 219 (160-247 [118-274]) s in Phase
      1 to 228 (151-501 [111-2661]) s in Phase 2. User feedback was positive and
      overall usability high (Phase 1--82%, Phase 2--78%).

PMID- 22861504
TI  - Analysis of data integrity.

PMID- 22861505
TI  - Respiratory arrest with remifentanil PCA.

PMID- 22861506
TI  - Respiratory arrest with remifentanil patient-controlled analgesia--another case.

PMID- 22861507
TI  - Remifentanil--was it only respiratory arrest?

PMID- 22861508
TI  - Remifentanil on the labour ward.

PMID- 22861509
TI  - Antibiotics, caesarean section and human error.

PMID- 22861510
TI  - Antibiotic prophylaxis for caesarean section.

PMID- 22861512
TI  - Induction for rapid sequence induction: a tri-deanery survey.

PMID- 22861513
TI  - Antibiotic or induction agent? Another problem from a possible solution.

PMID- 22861514
TI  - Simple modification for improved efficacy of intensive care unit bronchoscopy.

PMID- 22861515
TI  - Placement of a gastric tube using a flexible intubating fibrescope.

PMID- 22861516
TI  - Dynamic optimisation of the sniff position during laryngoscopy--an alternative
      technique.

PMID- 22861517
TI  - The accuracy of PiCCO(r) measurements in hypothermic post-cardiac arrest
      patients.

PMID- 22861518
TI  - Equipment manufacturers must differentiate auditory alarms for equipment used
      concurrently.

PMID- 22861519
TI  - Current BNF recommendations on peri-operative cessation of clopidogrel.

PMID- 22861520
TI  - Peri-operative anisocoria--the importance of pupil assessment before general
      anaesthesia.

PMID- 22861521
TI  - Does intrathecal analgesia reduce the subsequent minimum local analgesic
      concentration of epidural bupivacaine?

PMID- 22861523
TI  - Treatment satisfaction after switching to another therapy in Spanish orthopaedic
      clinic outpatients with knee or hip osteoarthritis previously refractory to
      paracetamol.
AB  - BACKGROUND AND OBJECTIVE: Hip and knee osteoarthritis is highly prevalent in the
      elderly, and the incidence is estimated to increase in the coming decades. Prior
      to surgery, symptomatic treatment, starting with non-pharmacological therapies,
      should be prescribed. Paracetamol (acetaminophen) is the recommended first
      pharmacological treatment for osteoarthritis. If paracetamol is ineffective, non
      steroidal anti-inflammatory drug (NSAID) treatment is indicated. The superiority
      of NSAIDs over paracetamol has been demonstrated in several studies. Furthermore,
      the assessment of patient satisfaction could be an adequate indicator of the
      quality of care given and is likely related to the evolution of the condition and
      the therapeutic regimen. The objective of this study was to assess the
      satisfaction of patients diagnosed with hip and/or knee osteoarthritis who had
      been previously treated with paracetamol and switched to NSAID treatment due to a
      lack of effectiveness by paracetamol. METHODS: An observational, prospective,
      multicentre and comparative study was conducted in 2009 among patients diagnosed
      with hip and knee OA who visited outpatient orthopaedic clinics. The evaluation
      of treatment effectiveness was carried out using a patient-based visual analogue
      scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC). The satisfaction regarding change of treatment due to a lack of
      effectiveness and/or the presence of adverse effects was evaluated using the
      osteoARthritis Treatment Satisfaction (ARTS) questionnaire. RESULTS: A total of
      2437 patients were evaluated (knee OA: 1438 [59%]; hip OA: 621 [25.5%]; knee and
      hip OA: 124 [5.1%]; and without OA location registered: 254 [10.4%]). The study
      findings showed an increase in patient satisfaction after abandoning the use of
      paracetamol to treat OA. Statistically significant increases in both overall
      satisfaction mean (from 57.7 [SD 13.5] to 71.3 [SD 12.0]) and in each of the four
      domains of the ARTS questionnaire were observed (p < 0.0001 in all cases).
      According to the WOMAC and a VAS, treatment effectiveness increased significantly
      after 3 months (p < 0.0001) and significant correlations with satisfaction were
      observed (r = -0.32 and r = -0.29, respectively; p < 0.0001). The mean (SD)
      change in global satisfaction in patients treated with NSAIDs was 14.9 (15.5)
      versus 7.2 (14.4) for patients treated with non-NSAIDs (p < 0.0001). Patients
      taking NSAID treatment showed substantially more improvement over those taking
      non-NSAID treatment. CONCLUSION: NSAIDs relieve pain due to OA in paracetamol
      resistant patients and improve treatment effectiveness and patient satisfaction
      with treatment. Furthermore, paracetamol-refractory subjects under conventional
      medical treatment with NSAIDs experienced the drug as more effective and also
      tended to be more satisfied with treatment than those treated with non-NSAIDs.

PMID- 22861524
TI  - Objective and subjective measures of sleepiness, and their associations with on
      road driving events in shift workers.
AB  - To assess the relationships between sleepiness and the incidence of adverse
      driving events in nurses commuting to and from night and rotating shifts, 27
      rotating and permanent night shift-working nurses were asked to complete daily
      sleep and duty logs, and wear wrist-activity monitors for 2 weeks (369 driving
      sessions). During all commutes, ocular measures of drowsiness, including the
      Johns Drowsiness Scale score, were assessed using the OptalertTM system.
      Participants self-reported their subjective sleepiness at the beginning and end
      of each drive, and any events that occurred during the drive. Rotating shift
      nurses reported higher levels of sleepiness compared with permanent night shift
      nurses. In both shift-working groups, self-reported sleepiness, drowsiness and
      drive events were significantly higher during commutes following night shifts
      compared with commutes before night shifts. Strong associations were found
      between objective drowsiness and increased odds of driving events during commutes
      following night shifts. Maximum total blink duration (mean = 7.96 s) during the
      drive and pre-drive Karolinska Sleepiness Scale (mean = 5.0) were associated with
      greater incidence of sleep-related events [OR, 5.35 (95% CI, 1.32, 21.60), OR,
      1.69 (95% CI, 1.04, 2.73), respectively]. Inattention was strongly associated
      with a Johns Drowsiness Scale score equal to or above 4.5 [OR, 4.58 (95% CI, 1.26
      16.69)]. Hazardous driving events were more likely to occur when drivers had been
      awake for 16 h or more [OR, 4.50 (95% CI, 1.81, 11.16)]. Under real-world driving
      conditions, shift-working nurses experience high levels of drowsiness as
      indicated by ocular measures, which are associated with impaired driving
      performance following night shift work.

PMID- 22861526
TI  - Fructose-water-dimethylsulfoxide interactions by vibrational spectroscopy and
      molecular dynamics simulations.
AB  - The solvation of fructose in dimethyl sulfoxide (DMSO) and DMSO-H(2)O (or DMSO
      D(2)O) mixtures was investigated using vibrational spectroscopy (Raman, ATR/FTIR)
      and molecular dynamics (MD) simulations. The analysis of the fructose hydroxyl
      hydrogen-DMSO oxygen radial distribution function showed that the coordination
      number of DMSO around the furanose form of fructose is ~3.5. This number is
      smaller than the number of hydroxyl groups of fructose because one DMSO molecule
      is shared between two hydroxyl groups and because intramolecular hydrogen bonds
      are formed. In the case of fructose-DMSO mixtures, a red shift of the Raman S?O
      asymmetric stretch is observed, which indicates that fructose breaks the DMSO
      clusters through strong hydrogen bonding between the hydrogen atoms of its
      hydroxyl groups and the oxygen atom of DMSO. The Raman scattering cross sections
      of the DMSO S?O stretch when a DMSO molecule interacts with another DMSO
      molecule, a fructose molecule, or a water molecule were estimated from the
      spectra of the binary mixtures using the coordination numbers from MD
      simulations. It was also possible to use these values together with the MD
      estimated coordination numbers to satisfactorily predict the effect of the water
      fraction on the Raman scattering intensity of the S?O stretching band in ternary
      mixtures. MD simulations also showed that, with increasing water content, the
      DMSO orientation around fructose changed, with the sulfur atom moving away from
      the carbohydrate. The deconvolution of the fructose IR OH stretching region
      revealed that the hydroxyls of fructose can be separated into two groups that
      participate in hydrogen bonds of different strengths. MD simulations showed that
      the three hydroxyls of the fructose ring form stronger hydrogen bonds with the
      solvent than the remaining hydroxyls, providing an explanation for the
      experimental observations. Finally, analysis of ATR/FTIR spectra revealed that,
      with increasing water content, the average hydrogen-bond enthalpy of the fructose
      hydroxyls decreases by ~2.5 kJ/mol.

PMID- 22861527
TI  - Pseudonegative thermal expansion and the state of water in graphene oxide layered
      assemblies.
AB  - Unraveling the complex interplay between thermal properties and hydration is a
      part of understanding the fundamental properties of many soft materials and very
      essential for many applications. Here we show that graphene oxide (GO)
      demonstrates a highly negative thermal expansion (NTE) coefficient owing to
      unique thermohydration processes related with fast transport of water between the
      GO sheets, the amphiphilic nature of nanochannels, and close-to-zero intrinsic
      thermal expansion of GO. The humidity-dependent NTE of GO layered assemblies, or
      "pseudonegative thermal expansion" (PNTE), differs from that of other hygroscopic
      materials due to its relatively fast and highly reversible expansion/contraction
      cycles and occurrence at low humidity levels while bearing similarities to
      classic NTE. Thermal expansion of polyvinyl alcohol/GO composites is easily
      tunable with additional intricacy of thermohydration effects. PNTE combined with
      isotropy, nontoxicity, and mechanical robustness is an asset for applications of
      actuators, sensors, MEMS devices, and memory materials and crucial for developing
      methods of thermal/photopatterning of GO devices.

PMID- 22861528
TI  - Epidemiology of human furuncular myiasis of Cordylobia anthropophaga (Grunberg)
      in Nigeria.
AB  - Two hundred people were randomly selected for myiasis infection in the Niger
      Delta region of Nigeria, except in some states where we did not get the
      stipulated number (200) to sample. In each of the six states sampled within the
      Niger Delta in 2009, 88% of 200 patients examined in Rivers State had the
      Cordylobia infection followed by Cross Rivers State (>86%), Bayelsa (>84%) while
      Edo, Delta, and Akwa Ibom states showed higher than 82% infection in that order.
      Our findings showed that women, children, and infants are commonly affected by
      furuncular myiasis irrespective of skin color, age, blood group, race, sex,
      genotype, etc. Infection due to C. anthropophaga occurs throughout the year; the
      rate of infection is higher during the rainy season (when humidity is normally
      higher) than the dry seasons. Most cases of human myiasis are not reported but
      treated locally. The Niger Delta populace (especially the areas sampled) consists
      of people with diverse occupations; some are fishermen, traders, farmers, and
      refuse disposers. They move from one place to another predisposed to myiasis
      causing agents due to the types of work they do. Two major categories of people
      based on skin color (i.e., white and black skinned) are recognized for this
      research. People with albinism are also part of the colored African group,
      however, according to the data, there does not seem to be any difference between
      them and others. Cordylobia infection is a neglected disease of the Niger Delta
      region. Therefore, there was the need to know the spread and factors that promote
      spreading as well as populations of the myiasis-causing agent in the Niger Delta.
      The data presented here provides good travel information to the Niger Delta
      region as well as other parts of Nigeria. Human furuncular myiasis affects
      neonates ranging from 3 to 11 days old, children, and adults in Nigeria. C.
      anthropophaga maggots penetrate all types of skin; people with albinism, white
      skin, and black skin. Some of the factors that affect the distribution include
      unhygienic situations, high humidity, poverty, and use of soiled clothes. Details
      of our findings are presented.

PMID- 22861645
TI  - Site-specific retention of colloids at rough rock surfaces.
AB  - The spatial deposition of polystyrene latex colloids (d = 1 MUm) at rough mineral
      and rock surfaces was investigated quantitatively as a function of Eu(III)
      concentration. Granodiorite samples from Grimsel test site (GTS), Switzerland,
      were used as collector surfaces for sorption experiments. At a scan area of 300 *
      300 MUm(2), the surface roughness (rms roughness, Rq) range was 100-2000 nm,
      including roughness contribution from asperities of several tens of nanometers in
      height to the sample topography. Although, an increase in both roughness and
      [Eu(III)] resulted in enhanced colloid deposition on granodiorite surfaces,
      surface roughness governs colloid deposition mainly at low Eu(III) concentrations
      (<=5 * 10(-7) M). Highest deposition efficiency on granodiorite has been found at
      walls of intergranular pores at surface sections with roughness Rq = 500-2000 nm.
      An about 2 orders of magnitude lower colloid deposition has been observed at
      granodiorite sections with low surface roughness (Rq < 500 nm), such as large and
      smooth feldspar or quartz crystal surface sections as well as intragranular
      pores. The site-specific deposition of colloids at intergranular pores is induced
      by small scale protrusions (mean height = 0.5 +/- 0.3 MUm). These protrusions
      diminish locally the overall DLVO interaction energy at the interface. The
      protrusions prevent further rolling over the surface by increasing the
      hydrodynamic drag required for detachment. Moreover, colloid sorption is favored
      at surface sections with high density of small protrusions (density (D) = 2.6 +/-
      0.55 MUm(-1), asperity diameter (phi) = 0.6 +/- 0.2 MUm, height (h) = 0.4 +/- 0.1
      MUm) in contrast to surface sections with larger asperities and lower asperity
      density (D = 1.2 +/- 0.6 MUm(-1), phi = 1.4 +/- 0.4 MUm, h = 0.6 +/- 0.2 MUm).
      The study elucidates the importance to include surface roughness parameters into
      predictive colloid-borne contaminant migration calculations.

PMID- 22861646
TI  - Super high resolution for single molecule-sequence-based typing of classical HLA
      loci at the 8-digit level using next generation sequencers.
AB  - Current human leukocyte antigen (HLA) DNA typing methods such as the sequence
      based typing (SBT) and sequence-specific oligonucleotide (SSO) methods generally
      yield ambiguous typing results because of oligonucleotide probe design
      limitations or phase ambiguity for HLA allele assignment. Here we describe the
      development and application of the super high-resolution single-molecule sequence
      based typing (SS-SBT) of HLA loci at the 8-digit level using next generation
      sequencing (NGS). NGS which can determine an HLA allele sequence derived from a
      single DNA molecule is expected to solve the phase ambiguity problem. Eight
      classical HLA loci-specific polymerase chain reaction (PCR) primers were designed
      to amplify the entire gene sequences from the enhancer-promoter region to the 3'
      untranslated region. Phase ambiguities of HLA-A, -B, -C, -DRB1 and -DQB1 were
      completely resolved and unequivocally assigned without ambiguity to single HLA
      alleles. Therefore, the SS-SBT method described here is a superior and effective
      HLA DNA typing method to efficiently detect new HLA alleles and null alleles
      without ambiguity.

PMID- 22861647
TI  - Pancreatic metastasis from osteosarcoma and Ewing sarcoma: literature review.
AB  - OBJECTIVES: Pancreatic metastasis from osteosarcoma and Ewing sarcoma is
      extremely rare. Differential diagnosis with primary pancreatic carcinoma is
      crucial before any treatment, but may be very difficult. MATERIAL AND METHODS: We
      searched for and reviewed the cases reported in the English literature. RESULTS:
      Twelve cases were identified, including nine osteosarcoma patients and three
      Ewing sarcoma cases. The median time between the sarcoma diagnosis and that of
      pancreatic metastasis was 3 years. In most of the cases, the pancreatic relapse
      followed or was associated with relapse(s) in one or more sites. Two out of eight
      patients with available follow-up were alive without disease 6+ and 11+ months
      after complete surgical removal, whereas five patients died from disease.
      Histological diagnosis was obtained before surgery in only five cases using
      percutaneous Tru-Cut biopsy in three cases and endoscopic ultrasound-guided fine
      needle aspiration biopsy (EUS-FNAB) in the two most recent ones. CONCLUSIONS:
      Osteosarcoma or Ewing sarcoma metastasis should be included in the differential
      diagnosis of pancreatic solid lesion, particularly in patients with a primary
      tumor. In this context, EUS and EUS-FNAB are reliable methods for the pre
      operative diagnosis and should thus be discussed before any therapeutic decision.

PMID- 22861648
TI  - Canine and feline pancreatic lipase immunoreactivity.
AB  - The diagnosis of pancreatitis in dogs and cats can be challenging. Several
      diagnostic tests have been evaluated over the years, but the majority have been
      shown to be of limited utility owing to poor performance or limited availability
      or because invasive procedures are required. Assays for the measurement of
      pancreatic lipase immunoreactivity (cPLI for dogs and fPLI for cats) were first
      developed over a decade ago and now include Spec cPL and SNAP cPL for dogs and
      Spec fPL and SNAP fPL for cats. Owing to their high sensitivity and specificity
      for pancreatitis compared with those of other serum tests, concentrations of cPLI
      and fPLI have been demonstrated to be the serum tests of choice for evaluation of
      dogs and cats, respectively, suspected of having pancreatitis. False-positive and
      false-negative results can occur, and recognition of the limitations of
      pancreatic lipase immunoreactivity assays is important. As there is currently no
      gold standard for antemortem diagnosis of pancreatitis in dogs and cats, the
      combination of a complete history and physical examination, measurement of
      pancreatic lipase immunoreactivity, and ultrasonographic examination of the
      pancreas is the best approach for an accurate noninvasive diagnosis of
      pancreatitis.

PMID- 22861650
TI  - Finding the issues, creating the science, mastering the art.

PMID- 22861649
TI  - A re-evaluation of 9-HODE activity at TRPV1 channels in comparison with
      anandamide: enantioselectivity and effects at other TRP channels and in sensory
      neurons.
AB  - BACKGROUND AND PURPOSE: Two oxidation products of linoleic acid, 9- and 13
      hydroxy-octadecadienoic acids (HODEs), have recently been suggested to act as
      endovanilloids, that is, endogenous agonists of transient receptor potential
      vanilloid-1 (TRPV1) channels, thereby contributing to inflammatory hyperalgesia
      in rats. However, HODE activity at rat TRPV1 in comparison with the best
      established endovanilloid, anandamide, and its enantioselectivity and selectivity
      towards other TRP channels that are also abundant in sensory neurons have never
      been investigated. EXPERIMENTAL APPROACH: We studied the effect of 9(R)-HODE,
      9(S)-HODE, (+/-)13-HODE, 15(S)-hydroxyanandamide and anandamide on [Ca(2+) ](i) 
      in HEK-293 cells stably expressing the rat or human recombinant TRPV1, or rat
      recombinant TRPV2, TRPA1 or TRPM8, and also the effect of 9(S)-HODE in rat dorsal
      root ganglion (DRG) neurons by calcium imaging. KEY RESULTS: Anandamide and 15(S)
      hydroxyanandamide were the most potent endovanilloids at human TRPV1, whereas
      9(S)-HODE was approximately threefold less efficacious and 75- and 3-fold less
      potent, respectively, and did not perform much better at rat TRPV1. The 9(R)-HODE
      and (+/-)13-HODE were almost inactive at TRPV1. Unlike anandamide and 15(S)
      hydroxyanandamide, all HODEs were very weak at desensitizing TRPV1 to the action
      of capsaicin, but activated rat TRPV2 [only (+/-)13-HODE] and rat TRPA1, and
      antagonized rat TRPM8, at concentrations higher than those required to activate
      TRPV1. Finally, 9(S)-HODE elevated [Ca(2+) ](i)  in DRG neurons almost
      exclusively in capsaicin-sensitive cells but only at concentrations between 25
      and 100 MUM. CONCLUSIONS AND IMPLICATIONS: The present data suggest that HODEs
      are less important endovanilloids than anandamide. 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- 22861651
TI  - Sex work in trucking milieux: "lot lizards," truckers, and risk.
AB  - BACKGROUND: Long-haul truckers often engage in risk-laden sexual mixing and drug
      exchanges with female sex workers while on the road, which increase their
      vulnerability to sexually transmitted infections/blood borne infections
      (STI/BBI). OBJECTIVE: An ethnoepidemiological study of STI/BBI in trucker
      centered populations was conducted at four truckstops in the United States. This
      article reports findings from an analysis of the female sex worker data, which
      show how mobility and transience, as well as poverty, homelessness, and exposure
      to violence, have the potential to exacerbate the occupational health risks of
      female sex workers. METHODS: Phase 1 involved nonparticipant observation of
      trucker risk network groups in public and semi-public settings at two Arizona
      truckstops. Phase 2 was a large-scale ethnoepidemiological study of STI/BBI risk
      among trucker networks at two Georgia truckstops. Ten sex workers in Phoenix and
      29 in Atlanta were interviewed individually or in focus groups. Textual data were
      analyzed using QSR NVivo 8 and serological data collected from the Georgia sample
      were analyzed for STIs/HIV. RESULTS: Infections occur within these populations,
      where the existence of multiple risks delivered via multiple channels within
      physical proximity maintains infection and transmission. CONCLUSIONS:
      Environmental-level interventions, such as better security at truck stops, and
      individual-level interventions, such as STI/BBI infection education and testing
      for FSWs and truckers, can contribute to safer settings for truckers, sex
      workers, and their sex and drug partners.

PMID- 22861653
TI  - Self-efficacy with application to nursing education: a concept analysis.
AB  - TOPIC: Concept analysis and self-efficacy. PURPOSE: This article analyzes the
      concept self-efficacy and its relationship to nursing education using Walker and
      Avant's methodology. SOURCES: Published literature. CONCLUSION: Nursing
      literature suggests increasing students' perceived self-efficacy will help to
      narrow the theory-practice gap. Self-efficacy is a cognitive variable that
      affects performance behaviors and affective processes. Perceived self-efficacy
      can be influenced by a direct experience, vicarious experience, or verbal
      persuasion. Individuals with high levels of self-efficacy demonstrate the
      defining attributes of confidence, perceived capability, and perseverance.

PMID- 22861652
TI  - Exploring the concept of HIV-related stigma.
AB  - BACKGROUND: HIV infection is a chronic, manageable illness. Despite advances in
      the care and treatment of people living with HIV infection, HIV-related stigma
      remains a challenge to HIV testing, care, and prevention. Numerous studies have
      documented the impact of HIV-related stigma among various groups of people living
      with HIV infection, but the concept of HIV-related stigma remains unclear.
      PURPOSE: Concept exploration of HIV-related stigma via an integrative literature
      review was conducted in order to examine the existing knowledge base of this
      concept. METHODS: Search engines were employed to review the existing knowledge
      base of this concept. CONCLUSION: After the integrative literature review, an
      analysis of HIV-related stigma emerged. Implications for future concept analysis,
      research, and practice are included.

PMID- 22861654
TI  - A concept development of the village health worker.
AB  - PROBLEM: Village health workers (VHWs) promote health and provide basic health
      care in areas of the world where basic health knowledge and health professionals
      are scarce. The 1960s-1980s saw a dramatic increase in the training of VHWs in
      resource-limited environments. Politics changed, disillusionment set in, and
      enthusiasm waned. Recently, increased pressures on health resources have led to
      the resurgence of VHWs. Until the shortage of health professionals is alleviated,
      the need for VHWs to extend the reach of scientifically verified health care into
      remote and conflict areas will remain acute. This need provides a compelling
      reason to pursue research concerning VHWs. Village health workers are usually
      trained by professional nurses and refer patients to them, so nursing is
      positioned to lead this important research. METHODS: The author developed the
      concept of the VHW using Meleis's Integrated Approach. Meleis's approach was
      chosen because it is appropriate for undeveloped concepts, emphasizes exploration
      and discovery, and can begin with clinical practice, taking advantage of the
      author's experience with VHWs. RESULTS: The resultant concept definition, with
      antecedents and consequences, provides a foundation other nurse researchers can
      build upon. Existing research concerning VHWs was reviewed and gaps suitable for
      future nursing research were identified.

PMID- 22861655
TI  - Sleep quality of hospitalized patients in surgical units.
AB  - AIM: The aim of this study was to determine the sleep quality of the patients
      hospitalized in surgical units and the factors that influence it. METHOD: The
      research was a randomized descriptive study. It was conducted in the surgical
      clinics of Sivas Cumhuriyet University Health Services Research Hospital. A total
      of 411 patients participated in the study. The research data were gathered by
      means of the Pittsburgh Sleep Quality Index (PSQI) and the Questionnaire aimed at
      capturing personal information about the participant patients and the factors
      influencing their sleep. RESULTS: The sleep quality score of the patients "during
      the last week" (8.090 +/- 3.504) was higher than their score in the
      "preadmission" period (4.229 +/- 2.726) (p= .000). The sleep quality scores of
      "the patients with previous hospitalization and operation experience" (p= .000),
      "those who had undergone a major surgical procedure" (p= .000), "those who had
      been hospitalized for a week" (p= .022), and "those undergoing medical
      intervention during sleeping hours" (p= .000) "during the last week" were high.
      Patients who had a chronic illness history and whose operations were postponed
      had poor quality of sleep in both the hospitalization and preadmission period (p=
      .000). CONCLUSIONS: It could be suggested that the patients in preoperative and
      postoperative periods cannot get adequate rest due to low sleep-quality levels.
      IMPLICATIONS FOR PRACTICE: Nurses can prepare an environment aiding sleep as a
      way to increase surgical patients' sleep quality in hospital.

PMID- 22861656
TI  - Nurse manager engagement: a concept analysis.
AB  - AIM: This concept analysis examines the visibility of nurse manager engagement in
      the healthcare work environment. BACKGROUND: The term employee engagement was
      derived from studies of morale or the willingness of a group to accomplish
      objectives in the 1920s. "Following World War II group morale scores were used as
      predictors of speed, quality, and militancy by US Army researchers. The goal was
      to identify star, or high performers. A term was needed to describe emotional
      attachment of an individual to the organization, fellow associates, and the job"
      ("Employee engagement origins," 2010, p. 1). DATA SOURCES: The CINAHL, MEDLINE,
      ABI INFORM, PsycINFO, and Ovid databases and the Internet were searched for the
      period of 2005-2010 for literature published in English with a focus on peer
      reviewed journals from disciplines of health sciences, health administration,
      business, and psychology. METHODS: The Walker and Avant method was used for this
      analysis. The experience of the author as a current and previous nurse manager
      was also used for this analysis. RESULTS: Nurse manager engagement was assumed to
      be present based indirectly on empirical referents and consequences, such as low
      or high vacancy rates for staff nurses. CONCLUSION: Further research is needed to
      explore the identity of the nurse serving in the role of manager/leader who is
      able to demonstrate the skills and talents necessary to visibly demonstrate
      engagement and facilitate a culture of engaged nurse managers.

PMID- 22861657
TI  - Function analysis of a bacterial tyrosine kinase, BtkB, in Myxococcus xanthus.
AB  - Myxococcus xanthus BtkB is composed of an N-terminal periplasmic domain and a C
      terminal cytoplasmic tyrosine kinase domain. The C-terminal cytoplasmic domain of
      BtkB was autophosphorylated in the presence of [gamma-(32) P]ATP and MgCl(2), and
      the autophosphorylated BtkB was detected with antiphosphotyrosine antibody,
      suggesting that BtkB is a bacterial tyrosine (BY) kinase. BY kinases have been
      demonstrated in the production of extracellular polysaccharide (EPS), antibiotic
      resistance, stress response, and DNA metabolism. Myxococcus xanthus btkB gene was
      expressed mainly in the growth phase and early stages of fruiting body
      development. When cultured in nutrient medium at high temperature (37  degrees
      C), btkB mutant showed reduced maximum cell density as compared to the wild type.
      Under starvation conditions, btkB mutant cells formed fruiting bodies and spores
      about 24 h later than the wild-type strain. The btkB mutant overproduced yellow
      pigment during development. Also, btkB mutant showed a decrease in EPS production
      when compared with the wild-type strain. These results suggested that BtkB may
      play multiple roles in M. xanthus cells.

PMID- 22861658
TI  - Endophytic bacterial communities in three arctic plants from low arctic fell
      tundra are cold-adapted and host-plant specific.
AB  - Endophytic bacteria inhabit internal plant tissues, and have been isolated from a
      large diversity of plants, where they form nonpathogenic relationships with their
      hosts. This study combines molecular and culture-dependent approaches to
      characterize endophytic bacterial communities of three arcto-alpine plant species
      (Oxyria digyna, Diapensia lapponica and Juncus trifidus) sampled in the low
      Arctic (69 degrees 03'N). Analyses of a 325 bacterial endophyte isolates, as well
      as seven clone libraries, revealed a high diversity. In particular, members of
      the Actinobacteria, Bacteroidetes, Firmicutes, Acidobacteria, and Proteobacteria
      were found. The compositions of the endophytic bacterial communities were
      dependent on host-plant species as well as on snow cover at sampling sites.
      Several bacterial genera were found to be associated tightly with specific host
      plant species. In particular, Sphingomonas spp. were characteristic for D.
      lapponica and O. digyna, and their phylogenetic grouping corresponded to the host
      plant. Most of the endophyte isolates grew well and retained activity at +4 
      degrees C, and isolate as well as clone library sequences were often highly
      similar to sequences from bacteria from cold environments. Taken together, this
      study shows that arctic plants harbour a diverse community of bacterial
      endophytes, a portion of which seems to be tightly associated with specific plant
      species.

PMID- 22861659
TI  - Orbital invasion by periocular infiltrating Basal cell carcinoma.

PMID- 22861660
TI  - Oxide- and zeolite-supported isostructural Ir(C2H4)2 complexes: molecular-level
      observations of electronic effects of supports as ligands.
AB  - Zeolite Hbeta- and gamma-Al(2)O(3)-supported mononuclear iridium complexes were
      synthesized by the reaction of Ir(C(2)H(4))(2)(acac) (acac is acetylacetonate)
      with each of the supports. The characterization of the surface species by
      extended X-ray absorption fine structure (EXAFS) and infrared (IR) spectroscopies
      demonstrated the removal of acac ligands during chemisorption, leading to the
      formation of essentially isostructural Ir(C(2)H(4))(2) complexes anchored to each
      support by two Ir-O(support) bonds. Atomic-resolution aberration-corrected
      scanning transmission electron microscopy (STEM) images confirm the spectra,
      showing only isolated Ir atoms on the supports with no evidence of iridium
      clusters. These samples, together with previously reported Ir(C(2)H(4))(2)
      complexes on zeolite HY, zeolite HSSZ-53, and MgO supports, constitute a family
      of isostructural supported iridium complexes. Treatment with CO led to the
      replacement of the ethylene ligands on iridium with CO ligands, and the nu(CO)
      frequencies of these complexes and white line intensities in the X-ray absorption
      spectra at the Ir L(III) edge show that the electron density on iridium increases
      in the following order on these supports: zeolite HY < zeolite Hbeta < zeolite
      HSSZ-53 ? gamma-Al(2)O(3) < MgO. The IR spectra of the iridium carbonyl complexes
      treated in flowing C(2)H(4) show that the CO ligands were replaced by C(2)H(4),
      with the average number of C(2)H(4) groups per Ir atom increasing as the amount
      of iridium was increasingly electron-deficient. In contrast to the typical
      supported catalysts incorporating metal clusters or particles that are highly
      nonuniform, the samples reported here, incorporating uniform isostructural
      iridium complexes, provide unprecedented opportunities for a molecular-level
      understanding of how supports affect the electronic properties, reactivities, and
      catalytic properties of supported metal species.

PMID- 22861661
TI  - General anaesthesia for emergency caesarean delivery: is the time saved worth the
      potential risks?

PMID- 22861662
TI  - Chlamydia trachomatis in fallopian tubes of women undergoing laparoscopy for
      ectopic pregnancy.
AB  - OBJECTIVES: To study whether Chlamydia trachomatis is absent or persists in a
      latent state in the fallopian tube at the time of laparoscopic salpingectomy for
      tubal ectopic pregnancy (EP). METHODS: We examined tissue of the fallopian tubes
      for the presence of C. trachomatis from women who underwent laparoscopic
      salpingectomy for EP. Presence or absence of C. trachomatis was assessed using
      both Probe Tec ET (define Tec and ET please) and real-time polymerase chain
      reaction (PCR) (Ausdiagnositic STD 6 assays) DNA amplification. RESULTS: Fresh
      tubal tissue from 17 women with histological confirmation of EP was examined in a
      hospital setting for the presence of C. trachomatis. The presence of C.
      trachomatis DNA was confirmed by PCR using a commercial test (BD ProbeTec ET
      System), and a real-time enhanced PCR able to detect few copies of the organism.
      Chlamydia DNA was detected in 0/16 tubal specimens, and in one case, the PCR
      analysis was not possible for presence of inhibitors. CONCLUSIONS: We did not
      find any evidence of latent infection of C. trachomatis in the fallopian tube at
      the time of laparoscopic salpingectomy for EP in our study. Although the numbers
      are small, our results suggest that EP can be considered a late complication of
      the tubal damage resulted from a previous acute Chlamydia infection and that EP
      may not be related to a latent persistence of Chlamydia in the fallopian tube.

PMID- 22861663
TI  - Cervical cancer incidence and mortality in Fiji 2003-2009.
AB  - BACKGROUND: Previous studies indicate that cervical cancer is the second most
      frequent cancer and most common cause of cancer mortality among women in Fiji.
      There is little published data on the epidemiology of cervical cancer in Pacific
      countries. AIMS: To determine the incidence 2003-2009 of, and mortality 2003-2008
      from, cervical cancer by ethnicity and period in Fiji, identify evidence of
      secular change and relate these data to other Pacific countries, Australia and
      New Zealand. METHODS: Counts of incident cervical cancer cases (2003-2009) and
      unit record mortality data (2003-2008) from the Fiji Ministry of Health were used
      to calculate age-standardised (to the WHO World Population) cervical cancer
      incidence and mortality rates, and cervical or uterine cancer mortality rates, by
      ethnicity, with 95% confidence intervals. On the basis of comparison of cervical
      cancer mortality with cervical or uterine cancer mortality in Fiji with similar
      populations, misclassification of cervical cancer deaths is unlikely. RESULTS:
      There is no evidence of secular change in cervical cancer incidence and mortality
      rates for the study period. For women of all ages and ethnicities, the age
      standardised incidence rate of cervical cancer (2003-2009) was 27.6 per 100,000
      (95% CI 25.4-29.8) and the age-standardised mortality rate (2003-2008) was 23.9
      per 100,000 (95% CI 21.5-26.4). The mortality/incidence ratio was 87%. Fijians
      had statistically significant higher age-standardised incidence and mortality
      rates than Indians. Fiji has one of the highest estimated rates of cervical
      cancer incidence and mortality in the Pacific region. CONCLUSION: Cervical cancer
      screening in Fiji needs to be expanded and strengthened.

PMID- 22861664
TI  - Re: Thromboprophylaxis in pregnancy.

PMID- 22861665
TI  - Re: Borbolla Foster A & Symonds I. A comparative study of the efficacy and
      outcomes of large loop excision of the transformation zone procedure performed
      under general versus local anaesthesia. ANZJOG 2012; 52: 128-132.

PMID- 22861666
TI  - Reversible fluorescence photoswitching in DNA.
AB  - We describe the engineering of reversible fluorescence photoswitching in DNA with
      high-density substitution, and its applications in advanced fluorescence
      microscopy methods. High-density labeling of DNA with cyanine dyes can be
      achieved by polymerase chain reaction using a modified DNA polymerase that has
      been evolved to efficiently incorporate Cy3- and Cy5-labeled cytosine base
      analogues into double-stranded DNA. The resulting biopolymer, "CyDNA", displays
      hundreds of fluorophores per DNA strand and is strongly colored and highly
      fluorescent, although previous observations suggest that fluorescence quenching
      at such high density might be a concern, especially for Cy5. Herein, we first
      investigate the mechanisms of fluorescence quenching in CyDNA and we suggest that
      two different mechanisms, aggregate formation and resonance energy transfer, are
      responsible for fluorescence quenching at high labeling densities. Moreover, we
      have been able to re-engineer CyDNA into a reversible fluorescence
      photoswitchable biopolymer by using the properties of the Cy3-Cy5 pair. This
      novel biopolymer constitutes a new class of photoactive DNA-based nanomaterial
      and is of great interest for advanced microscopy applications. We show that
      reversible fluorescence photoswitching in CyDNA can be exploited in optical lock
      in detection imaging. It also lays the foundations for improved and sequence
      specific super-resolution fluorescence microscopy of DNA. 

PMID- 22861667
TI  - Caring for women with chronic pelvic pain.

PMID- 22861668
TI  - Thirty years of preclinical safety evaluation of biopharmaceuticals: Did
      scientific progress lead to appropriate regulatory guidance?
AB  - INTRODUCTION: The first biopharmaceuticals were developed 30 years ago.
      Biopharmaceuticals differ significantly from small molecule therapeutics (SMTs).
      Because of such differences, it was expected that classical preclinical safety
      evaluation procedures applied to SMTs would not predict the adverse effects of
      biopharmaceuticals. Therefore, until sufficient experience was gained, the
      preclinical safety evaluation of biopharmaceuticals was carried out on a case-by
      case basis. 30 years of experience has since expanded the knowledge base in this
      area, in the hope to design a preclinical safety evaluation procedure suited to
      biopharmaceuticals. AREAS COVERED: This review describes how the preclinical
      safety evaluation of biopharmaceuticals has evolved. It shows that, as result of
      the risk-averse behavior of regulators and industry, classical procedures were
      taken as starting point although state-of-the-art knowledge on biopharmaceuticals
      was directed towards creating a new procedure, driven by the specific properties
      of biopharmaceuticals. EXPERT OPINION: Current preclinical safety evaluation
      guidance of biopharmaceuticals is criticized because it employs a checkbox
      approach. The adverse effects induced by biopharmaceuticals are on-target or
      immune system-induced, therefore, the preclinical safety evaluation should not be
      standardized, but rather driven by product specific safety concerns.

PMID- 22861669
TI  - A pathway to improved prospective observational post-authorization safety
      studies.
AB  - Randomized controlled trials (RCTs) are the gold standard for assessing the
      efficacy of drugs but not necessarily so for drug safety where inadequate power
      to detect either multiple or rare adverse events is a major handicap.
      Furthermore, the conditions under which drugs are approved for market use are
      often different from the settings in actual use. Indeed, with their control
      mechanisms, trials are by design largely inadequate for the identification of
      potential safety signals, especially of the rare type, hence the value of
      postmarketing surveillance and risk management plan-based activities. Today,
      clinical trials constitute only a part of the research that goes into assessing
      the safety of drugs. Observational studies, where the investigators merely
      collect data on treatments received by patients and their health status in
      routine clinical practice are increasing in uptake because they reflect the real
      life utility of drugs, despite the absence of random treatment assignment.
      Although such studies generally provide less compelling evidence than RCTs, they
      can be far more useful to drug safety assessment activities than generally
      acknowledged. An increasing number of post-authorization safety studies (PASS)
      within the European Medicines Agency's jurisdiction are of the observational type
      - considered perhaps as more appropriate vehicles for exploring and documenting
      how products perform in the real world. A similar trend is emerging in the US
      following the FDA Amendments Act of 2007; since early 2010, an increasing number
      of post-approval commitments mandated by the FDA include observational studies.
      However, despite this pattern, not much is known about ongoing efforts to address
      many of the recognized inadequacies associated with existing methodologies and
      practices currently adopted in observational PASS. This current opinion presents
      an overview of some of the main challenges we face in prospective observational
      PASS, mainly from practical experience, and proposes certain steps for
      improvement.

PMID- 22861672
TI  - Let's keep our 'eye on the ball': reducing tobacco-related harm.

PMID- 22861670
TI  - Methods for retrospective detection of drug safety signals and adverse events in
      electronic general practice records.
AB  - BACKGROUND: Examination of clinical data routinely recorded in general practice
      provides significant opportunities for identifying and quantifying medicine
      related adverse events not captured by spontaneous adverse reaction reporting
      systems. Robust pharmacovigilance methods for detecting and monitoring adverse
      events due to treatment with new and existing medicines are required to estimate
      the true extent of adverse events experienced by primary care patients.
      OBJECTIVES: The aim of the study was to examine evidence of adverse events
      contained in general practice electronic records and to study observed events
      related to selective serotonin reuptake inhibitors (SSRIs) as an example of drug
      specific pharmaceutical surveillance achievable with these data. METHODS:
      Electronic clinical records for a cohort of 338 931 patients consulting from 2002
      to 2007 were extracted from the patient management systems of 30 primary care
      clinics in New Zealand. Medical warnings files, prescription records and free
      text consultation notes were used to identify physician-recorded treatment
      cautions, including adverse events and medicines they were associated with. A
      structured chronological analysis of prescriptions, consultation notes and
      adverse events relating to patients prescribed the SSRI citalopram was
      undertaken, and included investigating reasons for switching treatment to another
      SSRI (fluoxetine or paroxetine) as a method for detecting evidence of drug safety
      signals. We compared the number of adverse events identified for patients at one
      practice with the number spontaneously reported to New Zealand's Centre for
      Adverse Reactions Monitoring (CARM). RESULTS: During the 6-year study period, 173
      478 patients received 4 811 561 prescriptions. There were 37 397 allergies,
      adverse events and other warnings recorded for 24 994 patients (7.4%); adverse
      events relating to 65 different types of drug were reported. Medicines most
      frequently implicated in adverse event reports were antibacterials, analgesics,
      antihypertensive medicines, lipid-modifying agents and skin preparations.
      Citalopram was prescribed for 5612 patients, and 701 adverse events relating to
      citalopram were identified in the electronic health records of 473 (8.4%)
      patients. A total of 713 (12.7%) patients changed treatment from citalopram to
      another SSRI, and 164 reasons for the switch were identified: suspected adverse
      drug effects for 129 (78.7%), lack of effect for 29 (17.7%) and patient
      preference for 6 (3.7%). The most common adverse events preceding the switch were
      anxiety, nausea and headaches. Of the 725 adverse events and medical warnings
      recorded at one practice, 21 (2.9%) were spontaneously reported to the CARM.
      CONCLUSIONS: Routinely recorded general practice data provide a wealth of
      opportunities for monitoring drug safety signals and for other patient safety
      issues. Medical warning records and consultation notes contain a wealth of
      information on adverse events but structured search methodologies are often
      required to identify these.

PMID- 22861673
TI  - Gambling in Australia: experiences, problems, research and policy.
AB  - AIMS: The aim of this paper is to provide a critical overview of the development
      and current status of gambling in Australia. METHODS: The paper examines the
      history and current status of gambling in Australia with a particular focus on
      the prevalence of problem gambling in the community and developments in policy
      and treatment services. RESULTS: The paper highlights the contradictory role of
      State governments as both providers of treatment services as well as agents for
      the liberalization for gambling. It also shows how the notion of 'addiction' is
      conceptualized in Australian research and treatment services, including the
      preference for harm-based and public health approaches. Such perspectives view
      problem gambling as having multiple pathways and determinants that extend beyond
      the pathology of individuals. CONCLUSIONS: Gambling in Australia provides a
      curious paradox. Highly liberalized State government policies that allow the
      proliferation of high intensity gambling coexist with extensive policy,
      regulation and research designed to address the negative impact of gambling on
      the Australian community.

PMID- 22861674
TI  - Commentary on Boschloo et al. (2012): persistence, natural recovery and
      recurrence of those with alcohol use disorders - does treatment make a
      difference?

PMID- 22861675
TI  - Commentary on Nosyk et al. (2012): detoxification from methadone maintenance
      therapy: how important is the exact technique that is used?

PMID- 22861676
TI  - Commentary on Boyd et al. (2012): debunking myths about methadone and crime.

PMID- 22861677
TI  - Commentary on Brunborg et al. (2012): future possibilities for investigating
      gambling and diminished aversive conditioning.

PMID- 22861678
TI  - The journal publishes both invited and unsolicited letters.

PMID- 22861680
TI  - Alcohol marketing policy: the missing evidence.

PMID- 22861682
TI  - Excellent outcomes after extratemporal epilepsy surgery in children.

PMID- 22861684
TI  - Porous, platinum nanoparticle-adsorbed carbon nanotube yarns for efficient fiber
      solar cells.
AB  - Pt is a classical catalyst that has been extensively used in fuel cell and solar
      cell electrodes, owing to its high catalytic activity, good conductivity, and
      stability. In conventional fiber-shaped solar cells, solid Pt wires are usually
      adopted as the electrode material. Here, we report a Pt nanoparticle-adsorbed
      carbon nanotube yarn made by solution adsorption and yarn spinning processes,
      with uniformly dispersed Pt nanoparticles through the porous nanotube network. We
      have fabricated TiO(2)-based dye-sensitized fiber solar cells with a Pt-nanotube
      hybrid yarn as counter electrode and achieved a power conversion efficiency of
      4.85% under standard illumination (AM1.5, 100 mW/cm(2)), comparable to the same
      type of fiber cells with a Pt wire electrode (4.23%). Adsorption of Pt
      nanoparticles within a porous nanotube yarn results in enhanced Pt-electrolyte
      interfacial area and significantly reduced charge-transfer resistance across the
      electrolyte interface, compared to a pure nanotube yarn or Pt wire. Our porous Pt
      nanotube hybrid yarns have the potential to reduce the use of noble metals, lower
      the device weight, and improve the solar cell efficiency.

PMID- 22861685
TI  - The alliance negotiation scale: psychometric construction and preliminary
      reliability and validity analysis.
AB  - Current measures of the working alliance tend to emphasize the degree of
      agreement or collaboration between patient and therapist about therapeutic tasks
      and goals. There are, however, both theoretical and empirical grounds to suggest
      that the degree to which patient and therapist are able to constructively
      negotiate disagreements about tasks and goals is another important dimension of
      the alliance. The present study outlines the preliminary development and
      evaluation of a measure to operationalize this dimension. This measure, the
      alliance negotiation scale (ANS), is a 12-item patient self-report instrument.
      Exploratory factor analysis and expert ratings informed the development of the
      scale, which consists of two distinct factors that demonstrate good internal
      consistency. Correlations between these factors and the working alliance offer
      preliminary support for its construct validity. A working version of the ANS is
      presented and the need for further validation is discussed.

PMID- 22861686
TI  - Deposition of Cryptosporidium parvum oocysts in porous media: a synthesis of
      attachment efficiencies measured under varying environmental conditions.
AB  - An extensive set of column experiments was performed with freshly harvested
      Cryptosporidium parvum oocysts to evaluate the effects of solution chemistry,
      surface coatings, interactions with other suspended particles, and pore fluid
      velocity on the fate and transport of this widely occurring waterborne pathogen
      in sandy porous media. We synthesized our data set with a comprehensive
      literature survey of similar experiments, to compute attachment (collision)
      efficiencies (alpha) used in colloid filtration theory (CFT) using three models
      for the single collector efficiency (eta) across a wide range of experimental
      conditions. Most prior experiments have observed the transport of surface
      treated, sterile C. parvum oocyst in porous media. Our column data confirm for
      freshly harvested oocysts that the presence of iron coatings on the sand medium
      and the presence of suspended illite clay drastically enhance oocyst deposition.
      Increasing ionic strength and decreasing pH also systematically enhance the
      attachment efficiency. Attachment efficiency decreases only at a very high ionic
      strength, most likely as a result of steric repulsion and possibly other changes
      in oocyst surface properties. Attachment efficiencies vary with fluid flow rate
      but without showing specific trends. We found that the computed attachment
      efficiency across all reported experiments could be reliably estimated using a
      regression model based on parameters related to ionic strength and pH. The
      regression model performed better with the Nelson-Ginn eta model and Tufenkji
      Elimelech eta model than with the Rajagopalan-Tien eta model. When CFT is used in
      environmental assessments, the proposed regression model provides a practical
      estimator for attachment efficiencies of C. parvum oocyst deposition in porous
      media for a variety of environmental conditions unfavorable to attachment.

PMID- 22861687
TI  - Evaluation of sequence-specific priming and real-time polymerase chain reaction
      assays for detecting HLA-B*51 alleles confirmed by sequence-based typing.
AB  - The human leukocyte antigen (HLA)-B*51 genotype is one of the well-known genetic
      factors associated with the development of Behcet's disease. We evaluated three
      sequence-specific priming (SSP) assays and one real-time PCR assay for detecting
      HLA-B*51 alleles using 93 whole blood samples, which were genotyped by high
      resolution sequence-based typing (SBT). All HLA-B*51 alleles determined by SBT
      were detected by the four evaluated assays, and the results for all HLA-B alleles
      other than HLA-B*51 were negative on all assays. Thus, all HLA-B51 tests showed
      100% sensitivity and 100% specificity for detecting HLA-B*51 alleles. The three
      SSP assays and the real-time PCR test for HLA-B*51 genotyping are simple, but
      reliable for detecting HLA-B*51 alleles in clinical laboratories.

PMID- 22861799
TI  - The effect of adalimumab for induction of endoscopic healing and normalization of
      mucosal cytokine gene expression in Crohn's disease.
AB  - OBJECTIVE: To investigate the effects of adalimumab on the induction of complete
      endoscopic healing and normalization of mucosal cytokine gene expression in
      patients with active Crohn's disease. MATERIAL AND METHODS: A prospective, single
      center study including 77 patients. All were examined by endoscopy before
      initiation of adalimumab induction therapy with a minimum of six adalimumab
      injections. Patients were treated until documentation of complete endoscopic
      healing. Biopsies for measurements of mRNA expression levels of interleukin(IL)
      17A (IL17A), IL23, interferon-gamma (IFNG), tumor necrosis factor-alpha (TNF),
      IL10 and Forkhead Box P3 (FOXP3), as well as for immunohistochemistry (IHC) were
      sampled at pre- and post-treatment endoscopy, and from 17 control patients.
      RESULTS: Complete endoscopic healing was achieved in 27.3% after 10 weeks of
      treatment, documented by endoscopy at week 12. Cumulative endoscopic healing
      after 52 weeks was 44.2%. Complete endoscopic healing led to a significant
      reduction in mRNA expression levels for all cytokines except IL10. Elevated
      expression of TNF and IL-17A persisted in 52% and 76%, respectively, of patients
      with complete endoscopic remission. Pre-treatment cytokine gene expression levels
      did not predict response to adalimumab therapy. CONCLUSIONS: Adalimumab induces
      accumulated complete endoscopic healing in 44% of patients after 52 weeks of
      therapy. Normalization of mucosal gene expression of cytokines does not occur in
      all patients with endoscopy-verified healed mucosa. Inclusion of normalized
      mucosal cytokine expression into the concept of mucosal healing could have an
      impact on long-term clinical outcome.

PMID- 22861800
TI  - Nutrition and Human Microbiome: 24 th Marabou Symposium, Stockholm, Sweden.
      Foreword.

PMID- 22861801
TI  - The impact of nutrition on the human microbiome.
AB  - Diet-derived carbohydrates that are not fully digested in the upper gut, known as
      nondigestible carbohydrates, provide a major source of energy for bacteria that
      colonize the human large intestine. It is well established that dietary intake of
      nondigestible carbohydrates influences microbial fermentation and total bacterial
      numbers in the colon. Recent evidence from molecular ecology has also shown that
      the amount and type of nondigestible carbohydrates (e.g., resistant starch, non
      starch polysaccharides, and prebiotics) influences the species composition of the
      intestinal microbiota both in short-term dietary interventions and in response to
      habitual long-term dietary intake. Interindividual variation in gut microbiota
      may, in part, reflect differences in dietary intake, but the response of the gut
      microbiota to dietary change can also differ among individuals. As a better
      understanding is gained of the impact of different groups of bacteria on host
      metabolism, the ability to manipulate the microbiota through diet should provide
      a route for delivering health benefits.

PMID- 22861802
TI  - Host responses to the human microbiome.
AB  - The human gut is home to vast numbers of bacteria (gut microbiota), which
      outnumber the cells in the human body by an order of magnitude. The gut
      microbiota has coevolved with humans and can be considered an organ of similar
      size as the liver, containing more than 1,000 cell types (bacterial species) and
      encoding 150-fold more genes than are present in the human genome. Accordingly,
      the gut microbiota may have profound effects on various host responses, either
      directly or indirectly, by modifying food components or endogenously produced
      molecules into signaling molecules. Recent findings suggest that an altered gut
      microbial composition is associated with inflammatory bowel disease and obesity,
      indicating that the gut microbiota should be considered a contributing factor in
      several common diseases.

PMID- 22861803
TI  - Microbiome and immunological interactions.
AB  - The healthy human gut supports a complex and diverse microbiota, dominated by
      bacterial phylotypes belonging to Bacteroidetes and Firmicutes. In the inflamed
      gut, overall diversity decreases, coincident with a greater representation of
      Proteobacteria. There is growing evidence supporting an important role for human
      gut bacteria in mucosal immunity; interactions at the level of both intestinal
      and colonic epithelial cells, dendritic cells, and T and B immune cells have been
      documented. These interactions influence gut barrier and defense mechanisms that
      include antimicrobial peptide and secretory IgA synthesis. The functional effects
      of commensal bacteria on T helper cell differentiation have led to the emerging
      concept that microbiota composition determines T effector- and T regulatory-cell
      balance, immune responsiveness, and homeostasis. The importance of this biology
      in relation to immune homeostasis, inflammatory bowel disease, and the rising
      incidence of autoimmune diseases will be discussed. The detailed description of
      the human gut microbiota, integrated with evidence-based mechanisms of immune
      modulation, provides an exciting platform for the identification of next
      generation probiotics and related pharmaceutical products.

PMID- 22861804
TI  - The human microbiome: ecosystem resilience and health.
AB  - Given the importance of the microbiome for human health, both the stability and
      the response to disturbance of this microbial ecosystem are crucial issues. Yet,
      the current understanding of these factors is insufficient. Early data suggest
      there is relative stability in the microbiome of adults in the absence of gross
      perturbation, and that long-term stability of the human indigenous microbial
      communities is maintained not by inertia but by the action of restorative forces
      within a dynamic system. After brief exposures to some antibiotics, there is an
      immediate and substantial perturbation and at least a partial recovery of
      taxonomic composition. Responses to antibiotics are individualized and are
      influenced by prior experience with the same antibiotic. These findings suggest
      that the human microbiome has properties of resilience. Besides serving to reveal
      critical underlying functional attributes, microbial interactions, and keystone
      species within the indigenous microbiota, the response to disturbance may have
      value in predicting future instability and disease and in managing the human
      microbial ecosystem.

PMID- 22861805
TI  - The microbiota in inflammatory bowel disease: friend, bystander, and sometime
      villain.
AB  - Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel
      disease, represent the heterogeneous outcome of three colliding influences:
      genetic risk factors, environmental modifiers, and immune effector mechanisms of
      tissue injury. The nature of these inputs is complex, with each having distinct
      and overlapping contributions to ulcerative colitis and Crohn's disease.
      Identification of specific genetic risk factors has improved the understanding of
      specific pathways to disease, but the primacy of environmental or lifestyle
      factors linked to changes in the gut microbiota, particularly in early life, is
      increasingly evident. Clarification of the molecular basis of host-microbe
      interactions in health and in susceptible individuals promises novel therapeutic
      strategies.

PMID- 22861807
TI  - Role of the intestinal microbiome in health and disease: from correlation to
      causation.
AB  - Recorded observations indicating an association between intestinal microbes and
      health are long-standing in terms of specific diseases, but emerging high
      throughput technologies that characterize microbial communities in the intestinal
      tract are suggesting new roles for the supposedly normal microbiome. This review
      considers the nature of the evidence supporting a relationship between the
      microbiota and the predisposition to disease as associative, correlative, or
      causal. Altogether, indirect or associative support currently dominates the
      evidence base, which now suggests that the intestinal microbiome can be linked to
      a growing number of over 25 diseases or syndromes. While only a handful of cause
      and-effect studies have been performed, this form of evidence is increasing. The
      results of such studies are expected to be useful in monitoring disease
      development, in providing a basis for personalized treatments, and in indicating
      future therapeutic avenues.

PMID- 22861806
TI  - Defining the human microbiome.
AB  - Rapidly developing sequencing methods and analytical techniques are enhancing our
      ability to understand the human microbiome, and, indeed, how the microbiome and
      its constituents are defined. This review highlights recent research that expands
      our ability to understand the human microbiome on different spatial and temporal
      scales, including daily time series datasets spanning months. Furthermore,
      emerging concepts related to defining operational taxonomic units, diversity
      indices, core versus transient microbiomes, and the possibility of enterotypes
      are discussed. Additional advances in sequencing technology and in our
      understanding of the microbiome will provide exciting prospects for exploiting
      the microbiota for personalized medicine.

PMID- 22861808
TI  - Discussion from the 24(th)  Marabou Symposium: Nutrition and the human
      microbiome.

PMID- 22861809
TI  - Summary of the 24(th) Marabou Symposium: Nutrition and the human microbiome.
AB  - This summary covers the articles and attributed discussion in the present
      supplement, which resulted from the 24(th)  Marabou Symposium titled "Nutrition
      and the Human Microbiome", which was held in Stockholm in 2011 with the
      participation of about 40 global experts in microbiology, physiology, biology,
      and medicine. The individual articles address a number of topics related to the
      human microbiome; the attributed discussion, however, offers much more on the
      nature of the current scientific debate and provides insight into new
      opportunities for research as well as possible effects of the gut microbes,
      ranging from possible prenatal epigenetic effects to brain function and behavior.

PMID- 22861811
TI  - Exciton relaxation in PbSe nanorods.
AB  - Measurements of the picosecond-time-scale dynamics of photoexcited electrons in
      PbSe nanorods are reported. The intraband (1Pi -> 1Sigma) relaxation occurs with
      a time constant of ~500 fs, which corresponds to a fast energy-relaxation rate of
      ~0.6 eV/ps. The biexciton lifetime in PbSe nanorods is significantly (3-4 times)
      longer than the lifetime of PbSe quantum dots with the same energy gap, roughly
      as expected considering the increased volume. The multiexciton lifetimes of PbSe
      nanorods scale as expected for a bimolecular recombination mechanism.
      Implications of the observed relaxations will be discussed.

PMID- 22861812
TI  - Angiogenic biomarkers for prediction of maternal and neonatal complications in
      suspected preeclampsia.
AB  - OBJECTIVE: To determine if maternal serum angiogenic factors predict maternal and
      neonatal complications in women presenting to an acute care setting with
      suspected preeclampsia. STUDY DESIGN: Maternal serum samples were prospectively
      collected from women with suspected preeclampsia at the time of initial
      presentation to hospital triage with signs or symptoms of preeclampsia. Soluble
      fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble
      endoglin (sEng) were measured by ELISA. The primary outcome was a composite of
      maternal and neonatal complications. RESULTS: Of 276 women with suspected
      preeclampsia, 78 developed maternal or neonatal complications. Among women
      presenting prior to 37 weeks gestation, sFlt1, PlGF, and sEng were significantly
      different in women who developed maternal and neonatal complications as compared
      to women without complications. Higher levels of sFlt1, sEng, and the sFlt1:PlGF
      ratio were associated with an increased odds of complications among women
      presenting prior to 37 weeks. A multivariable model combining the sFlt1:PlGF
      ratio with clinical variables was more predictive of complications (AUC 0.91, 95%
      CI 0.85-0.97) than a model using clinical variables alone (AUC 0.82, 95% CI 0.79
      0.90). CONCLUSION: Angiogenic biomarkers associate with maternal and neonatal
      complications in women with suspected preeclampsia, and may be useful for risk
      stratification.

PMID- 22861813
TI  - Novel beta-amino acid derivatives as inhibitors of cathepsin A.
AB  - Cathepsin A (CatA) is a serine carboxypeptidase distributed between lysosomes,
      cell membrane, and extracellular space. Several peptide hormones including
      bradykinin and angiotensin I have been described as substrates. Therefore, the
      inhibition of CatA has the potential for beneficial effects in cardiovascular
      diseases. Pharmacological inhibition of CatA by the natural product ebelactone B
      increased renal bradykinin levels and prevented the development of salt-induced
      hypertension. However, so far no small molecule inhibitors of CatA with oral
      bioavailability have been described to allow further pharmacological profiling.
      In our work we identified novel beta-amino acid derivatives as inhibitors of CatA
      after a HTS analysis based on a project adapted fragment approach. The new
      inhibitors showed beneficial ADME and pharmacokinetic profiles, and their binding
      modes were established by X-ray crystallography. Further investigations led to
      the identification of a hitherto unknown pathophysiological role of CatA in
      cardiac hypertrophy. One of our inhibitors is currently undergoing phase I
      clinical trials.

PMID- 22861814
TI  - Non-Gaussian statistics and nanosecond dynamics of electrostatic fluctuations
      affecting optical transitions in proteins.
AB  - We show that electrostatic fluctuations of the protein-water interface are
      globally non-Gaussian. The electrostatic component of the optical transition
      energy (energy gap) in a hydrated green fluorescent protein is studied here by
      classical molecular dynamics simulations. The distribution of the energy gap
      displays a high excess in the breadth of electrostatic fluctuations over the
      prediction of the Gaussian statistics. The energy gap dynamics include a
      nanosecond component. When simulations are repeated with frozen protein motions,
      the statistics shifts to the expectations of linear response and the slow
      dynamics disappear. We therefore suggest that both the non-Gaussian statistics
      and the nanosecond dynamics originate largely from global, low-frequency motions
      of the protein coupled to the interfacial water. The non-Gaussian statistics can
      be experimentally verified from the temperature dependence of the first two
      spectral moments measured at constant-volume conditions. Simulations at different
      temperatures are consistent with other indicators of the non-Gaussian statistics.
      In particular, the high-temperature part of the energy gap variance (second
      spectral moment) scales linearly with temperature and extrapolates to zero at a
      temperature characteristic of the protein glass transition. This result,
      violating the classical limit of the fluctuation-dissipation theorem, leads to a
      non-Boltzmann statistics of the energy gap and corresponding non-Arrhenius
      kinetics of radiationless electronic transitions, empirically described by the
      Vogel-Fulcher-Tammann law. 

PMID- 22861815
TI  - Missions and thoughts about Nordic College of Caring Science future.

PMID- 22861816
TI  - Functional electrical stimulation with exercises for standing balance and weight
      transfer in acute stroke patients: a feasibility randomized controlled trial.
AB  - OBJECTIVES: To test parameters needed for the design of a larger trial including
      the following: 1) identifying eligible participants, recruitment, and retention
      rates; 2) the feasibility and acceptability of delivering functional electrical
      stimulation (FES) to the gluteus maximus and quadriceps femoris for acute stroke
      patients in a hospital rehabilitation setting; 3) the outcome measures; 4)
      obtaining initial estimates of effect size; and 5) clarifying the relevant
      control group. MATERIALS AND METHODS: Twenty-one people with acute stroke-mean
      age = 68 (min to max: 33-87) years; weeks postonset = 4.6 (min to max: 1-14)-were
      randomized to three groups to receive two weeks of balance training with FES,
      balance training alone, or usual care. Symmetry in normal standing, weight
      transfer onto the affected limb, balance, mobility, and speed of walking were
      assessed before, shortly after the end of training, and two weeks later by a
      blinded assessor. RESULTS: 1) FES was successfully delivered but not with the
      planned eight sessions; 2) no trends in favor of FES were found; and 3) 4% of
      those screened took part but approaching 20% might be recruited in the future, no
      single outcome measure was suitable for all participants, and more routine
      physiotherapy was delivered to the control group. CONCLUSIONS: FES is feasible in
      this patient group but further feasibility and definitive trials are required.

PMID- 22861817
TI  - Differential expression of organic cation transporter OCT-3 in oral premalignant
      and malignant lesions: potential implications in the antineoplastic effects of
      metformin.
AB  - BACKGROUND: Recent evidence indicates that metformin, a biguanide used as first
      line treatment for type 2 diabetes, prevents the conversion of carcinogen-induced
      oral dysplasias into head and neck squamous cell carcinomas (HNSCC), most likely
      by inhibiting mammalian target of rapamycin complex 1 (mTORC1) oncogenic
      signaling. Whether metformin acts directly at the primary tumor site or
      indirectly by modulating hormonal secretion from extratumoral organs remains
      unknown. As organic cation transporters (OCT) belonging to the solute carrier 22A
      gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and
      activity, it is critical to define what role they play in the antineoplastic
      activity of metformin. METHODS: Immunohistochemical and immunoblotting techniques
      were used in normal, dysplastic and HNSCC tissues, and HNSCC cell lines,
      respectively, to determine OCTs expression levels. RESULTS: We report that only
      OCT-3 was highly expressed in a number of HNSCC cell lines, oral epithelial
      dysplasias, and well to moderately differentiated HNSCC. Indeed, inhibition of
      OCT-3 expression and activity in HNSCC cells prevented metformin-induced AMP
      activated protein kinase activation and mTORC1 pathway inhibition. Moreover, in
      oral dysplasias, high OCT-3 expression localized to epithelial compartments where
      mTORC1 signaling was also upregulated suggestive of a potential local effect of
      metformin. CONCLUSIONS: The concept of using metformin as a chemopreventive agent
      to control head and neck carcinogenesis is promising. Further work is warranted
      to elucidate largely unexplored mechanisms of metformin uptake and pharmacologic
      action that may ultimately influence the selection of the most suitable patients
      who can benefit from metformin in head and neck cancer chemoprevention.

PMID- 22861818
TI  - Registrar interest in academic obstetrics and gynaecology: a cross-sectional
      survey.
AB  - BACKGROUND: New Zealand has an urgent need to train and retain obstetrics and
      gynaecology academics, and postgraduate training pathways are being considered.
      AIMS: To gauge registrar interest in an academic training position and an
      academic career; analyse the importance of various encouraging factors; and
      investigate how demographics, experience and encouragers may be associated with
      academic interest. METHODS: All obstetric and gynaecology registrars working in
      New Zealand were invited by their clinical directors to participate in an online
      survey in March-June 2011. Statistical analysis, using Fisher's Exact and chi
      squared tests, was used to investigate how demographic, experience and encourager
      variables were associated with academic interest. RESULTS: Of the 58
      participants, 46 were women, 32 were New Zealand medical graduates and 43 were on
      the training program. Over half (54%) indicated they would consider a 1-year
      rotating research/teaching position and 45% an academic career. The most
      important encouraging factors for academic work were interest, opportunity to
      balance clinical and academic roles, job flexibility (lifestyle and family) and a
      supportive academic environment. Women were nearly nine times more likely to
      consider academic training (OR 8.75, P = 0.007), and trainees were one-third as
      likely to consider it compared to non-trainees (OR 0.31, P = 0.073). CONCLUSIONS:
      New Zealand has the unique ability to approach retention and training issues in a
      flexible and innovative manner which utilises international links. Clinical
      academic training positions should be set-up with quality supervision and support
      similar pay scales and the opportunity for simultaneous part-time clinical
      practice.

PMID- 22861819
TI  - A novel HLA-A31 allele, A*31:22, was identified by sequence-based typing.
AB  - The human leukocyte antigen HLA-A*31:22 allele shows a single nucleotide change
      at position 245 (A > C) of exon 2 from the closest matching allele HLA
      A*31:01:02.

PMID- 22861821
TI  - Cryptococcus species (Tremellales) from glacial biomes in the southern
      (Patagonia) and northern (Svalbard) hemispheres.
AB  - Cryptococcus species (Basidiomycota) were isolated as the predominant yeast from
      glacial biomes of both Patagonia (Argentina) and the Svalbard archipelago
      (Norway). For a selected group of Cryptococcus belonging to Tremellales,
      assimilative profile, production of extracellular hydrolytic enzymes and
      ribosomal DNA internal transcribed spacer and large subunit (D1/D2) sequences
      were analysed. Cryptococcus victoriae, which was originally described from
      Antarctica, was the most frequently found species at both locations. High
      variability within the species was observed and described at the genotypic and
      phenotypic levels, two newly described species were found in both Patagonia and
      Svalbard: Cryptococcus fonsecae and Cryptococcus psychrotolerans. Two other new
      species were found only in Patagonia: Cryptococcus frias and Cryptococcus
      tronadorensis. Three additional new taxa were found, but they are not named as
      they were only represented by single isolates.

PMID- 22861820
TI  - Glutaraldehyde erythropoietin protects kidney in ischaemia/reperfusion injury
      without increasing red blood cell production.
AB  - BACKGROUND AND PURPOSE: Recombinant human erythropoietin (rHuEPO) is currently
      the mainstay of renal anaemia treatment. Recently, rHuEPO has been shown to
      provide pleiotrophic tissue protection in various pathological conditions.
      However, the benefits of rHuEPO beyond anaemia treatment are limited because it
      increases red blood cell mass. Carbamylated erythropoietin (CEPO) is the first
      rHuEPO derivative that lacks erythropoietic activity but retains tissue
      protection properties. Since carbamylation targets lysine residues on rHuEPo, we
      hypothesized that targeted lysine modifications of rHuEPO may result in a novel
      non-erythropoietic erythropoietin. EXPERIMENTAL APPROACH: rHuEPO was subjected to
      various targeted lysine modifications. In vitro cytoprotection and apoptosis were
      evaluated using P19 and HEK293 cells. In vivo erythropoiesis was performed by
      administering the derivatives to animals for 2 weeks. Renoprotection was tested
      on an ischaemia/reperfusion (I/R) model. KEY RESULTS: We synthesized a novel
      derivative, a glutaraldehyde erythropoietin (GEPO). This construct abolished in
      vivo erythropoiesis. Biochemical characterization showed that GEPO was more
      electrostatically negative than rHuEPO. Immunoprecipitation experiments revealed
      that GEPO bound to the IL3RB/EPOR heterotrimeric receptor and ameliorated
      cellular apoptosis via the activation of Bcl-2. Notably, Bcl-2 activation was
      suppressed by the JAK2 inhibitor, tyrphostin AG490. In vivo experiments showed
      that GEPO also ameliorated kidney damage due to I/R injury both functionally and
      histologically. CONCLUSIONS AND IMPLICATIONS: Herein, we describe a novel lysine
      modified rHuEPO, glutaradehyde-EPO (GEPO), obtained from a simple reaction. This
      derivative has no erythropoietic properties but retains cell-protective
      characteristics both in vitro and in vivo, with promise for future use as an
      adjunctive treatment of kidney disease.

PMID- 22861822
TI  - The acute effects of physical activity on cigarette cravings: systematic review
      and meta-analysis with individual participant data.
AB  - AIMS: To conduct an updated systematic review and the first meta-analysis of
      experimental trials investigating the acute effects of short bouts of physical
      activity (PA) on strength of desire (SoD) and desire to smoke (DtS) using
      individual participant data (IPD). METHODS: A systematic review of literature and
      IPD meta-analyses included trials assessing the acute effects of shorts bouts of
      PA on SoD and DtS among temporarily abstaining smokers not using pharmaceutical
      aids for smoking cessation. Authors of eligible studies were contacted and raw
      IPD were obtained. Two-stage and one-stage IPD random-effects meta-analyses were
      conducted. Participants engaging in PA were compared against control
      participants, using post-intervention SoD and DtS with baseline adjustments.
      RESULTS: A two-stage IPD meta-analysis assessing effects of PA on SoD yielded an
      average standardized mean difference (SMD) between PA and control conditions
      (across 15 primary studies) of -1.91 [95% confidence interval (CI): -2.59 to 
      1.22]. A two-stage IPD meta-analysis assessing effects of PA on DtS yielded an
      average SMD between PA and control conditions (across 17 primary studies) of 
      2.03 (95% CI: -2.60 to -1.46). Additional meta-analyses, including those using a
      one-stage model, those including only parallel arm studies and meta-analyses
      comparing only moderate exercise against a control condition, showed significant
      craving reduction following PA. Despite a high degree of between-study
      heterogeneity, effects sizes of all primary studies were in the same direction,
      with PA showing a greater reduction in cravings compared with controls.
      CONCLUSIONS: There is strong evidence that physical activity acutely reduces
      cigarette craving.

PMID- 22861823
TI  - Providing holistic care for women with chronic pelvic pain.
AB  - Chronic pelvic pain (CPP) is one of the most common pain conditions affecting
      women and can have a significant impact on quality of life. Assessment of women
      with CPP is best approached in a comprehensive, systematic manner that includes
      exploration of physiological and psychological causes. A range of treatment
      options that draw from conventional medicine and complementary and alternative
      modalities should be offered. The women's health nurse plays a pivotal role in
      all aspects of care. 

PMID- 22861825
TI  - Temsirolimus: a safety and efficacy review.
AB  - INTRODUCTION: The vascular endothelial growth factor (VEGF) pathway and the
      mammalian Target of Rapamycin (mTOR) represent the most frequently exploited
      targets in renal cell carcinoma (RCC). Temsirolimus is an inhibitor of mTOR, and
      is a unique ester derivative of sirolimus, a macrocyclic lactone, with improved
      pharmaceutical properties, including stability and solubility. Temsirolimus binds
      to the cytoplasmic protein FKBP-12, and the complex binds and inhibits mTOR.
      AREAS COVERED: This review summarizes the clinical findings and safety of
      temsirolimus in RCC patients. EXPERT OPINION: A Phase III clinical trial has
      demonstrated that temsirolimus has statistically significant advantages over
      treatment with IFN-alpha in RCC patients with poor prognosis, in terms of OS
      (overall survival), PFS (progression-free survival), and tumor response. Median
      OS was improved 49% compared to IFN-alpha, and median PFS was approximately
      doubled. It is now considered the standard for RCC patients with poor prognostic
      features. The possibility that this agent is useful in metastatic non-clear cell
      carcinoma patients has also been suggested by a subset analysis of the pivotal
      Phase III trial. Studies in untreated favorable and intermediate risk clear cell
      and refractory mRCC patients are required.

PMID- 22861824
TI  - pH-Sensitive polymeric micelle-based pH probe for detecting and imaging acidic
      biological environments.
AB  - To overcome the limitations of monomeric pH probes for acidic tumor environments,
      this study designed a mixed micelle pH probe composed of polyethylene glycol
      (PEG)-b-poly(L-histidine) (PHis) and PEG-b-poly(L-lactic acid) (PLLA), which is
      well-known as an effective antitumor drug carrier. Unlike monomeric histidine and
      PHis derivatives, the mixed micelles can be structurally destabilized by changes
      in pH, leading to a better pH sensing system in nuclear magnetic resonance (NMR)
      techniques. The acidic pH-induced transformation of the mixed micelles allowed pH
      detection and pH mapping of 0.2-0.3 pH unit differences by pH-induced "on/off"
      like sensing of NMR and magnetic resonance spectroscopy. The micellar pH probes
      sensed pH differences in nonbiological phosphate buffer and biological buffers
      such as cell culture medium and rat whole blood. In addition, the pH-sensing
      ability of the mixed micelles was not compromised by loaded doxorubicin. In
      conclusion, PHis-based micelles could have potential as a tool to simultaneously
      treat and map the pH of solid tumors in vivo.

PMID- 22861826
TI  - Interpersonal processes affecting early alliance formation in experiential
      therapy for depression.
AB  - This study examined the effects of in-session interpersonal process and pre
      therapy interpersonal problems on session-one alliance formation for 32 clients
      who received short-term experiential therapy for depression. Interpersonal
      behavior measured by the Structural Analysis of Social Behavior, as well as
      clients' pre-therapy reports of interpersonal problems significantly related to
      session-one alliance scores. Greater client disclosure independently predicted a
      stronger session-one bond with the therapist. Both greater client disclosure
      (positively) and pre-therapy Social Inhibition (negatively) independently
      predicted early goal agreement. Findings suggest that client disclosure is a
      marker of early engagement in experiential therapy, as well as support this
      model's mandate to form interpersonally safe therapeutic environments from the
      first moments of therapy.

PMID- 22861827
TI  - Degeneracies in trapped two-component Fermi gases.
AB  - We report on previously unobserved intersystem degeneracies in two-component
      equal-mass Fermi gases with interspecies zero-range interactions under isotropic
      harmonic confinement. Over the past 10 years, two-component Fermi gases
      consisting of n1 spin-up and n2 spin-down atoms with interspecies zero-range
      interactions have become a paradigm for modeling condensed matter systems,
      nuclear matter, and neutron matter. We show that the eigenenergies of the (n1 +
      1, n2 - 1) system are degenerate with the eigenenergies of the (n1, n2) system
      for any s-wave scattering length a(s), including infinitely large, positive, and
      negative a(s). The existence of the intersystem degeneracies is demonstrated
      explicitly for few-body systems with n1 + n2 = 4, 5, and 6. The degeneracies and
      associated symmetries are explained within a group theoretical framework.

PMID- 22861828
TI  - Experimental investigation of the evolution of gaussian quantum discord in an
      open system.
AB  - Gaussian quantum discord is a measure of quantum correlations in gaussian
      systems. Using gaussian discord, we quantify the quantum correlations of a
      bipartite entangled state and a separable two-mode mixture of coherent states. We
      experimentally analyze the effect of noise addition and dissipation on gaussian
      discord and show that the former noise degrades the discord, while the latter
      noise for some states leads to an increase of the discord. In particular, we
      experimentally demonstrate the near death of discord by noisy evolution and its
      revival through dissipation.

PMID- 22861829
TI  - Optically guided beam splitter for propagating matter waves.
AB  - We study experimentally and theoretically a beam splitter setup for guided atomic
      matter waves. The matter wave is a guided atom laser that can be tuned from
      quasimonomode to a regime where many transverse modes are populated, and
      propagates in a horizontal dipole beam until it crosses another horizontal beam
      at 45 degrees . We show that depending on the parameters of this X configuration,
      the atoms can all end up in one of the two beams (the system behaves as a perfect
      guide switch), or be split between the four available channels (the system
      behaves as a beam splitter). The splitting regime results from a chaotic
      scattering dynamics. The existence of these different regimes turns out to be
      robust against small variations of the parameters of the system. From numerical
      studies, we also propose a scheme that provides a robust and controlled beam
      splitter in two channels only.

PMID- 22861830
TI  - Experimental demonstration of counterfactual quantum communication.
AB  - Quantum effects, besides offering substantial superiority in many tasks over
      classical methods, are also expected to provide interesting ways to establish
      secret keys between remote parties. A striking scheme called "counterfactual
      quantum cryptography" proposed by Noh [Phys. Rev. Lett. 103, 230501 (2009).]
      allows one to maintain secure key distributions, in which particles carrying
      secret information are seemingly not being transmitted through quantum channels.
      We have experimentally demonstrated, for the first time, a faithful
      implementation for such a scheme with an on-table realization operating at
      telecom wavelengths. To verify its feasibility for extension over a long
      distance, we have furthermore reported an illustration on a 1 km fiber. In both
      cases, high visibilities of more than 98% are achieved through active
      stabilization of interferometers. Our demonstration is crucial as a direct
      verification of such a remarkable application, and this procedure can become a
      key communication module for revealing fundamental physics through
      counterfactuals.

PMID- 22861831
TI  - Quantum adiabatic algorithm and scaling of gaps at first-order quantum phase
      transitions.
AB  - Motivated by the quantum adiabatic algorithm (QAA), we consider the scaling of
      the Hamiltonian gap at quantum first-order transitions, generally expected to be
      exponentially small in the size of the system. However, we show that a quantum
      antiferromagnetic Ising chain in a staggered field can exhibit a first-order
      transition with only an algebraically small gap. In addition, we construct a
      simple classical translationally invariant one-dimensional Hamiltonian containing
      nearest-neighbor interactions only, which exhibits an exponential gap at a
      thermodynamic quantum first-order transition of essentially topological origin.
      This establishes that (i) the QAA can be successful even across first-order
      transitions but also that (ii) it can fail on exceedingly simple problems readily
      solved by inspection, or by classical annealing.

PMID- 22861832
TI  - Virtual parallel computing and a search algorithm using matrix product states.
AB  - We propose a form of parallel computing on classical computers that is based on
      matrix product states. The virtual parallelization is accomplished by
      representing bits with matrices and by evolving these matrices from an initial
      product state that encodes multiple inputs. Matrix evolution follows from the
      sequential application of gates, as in a logical circuit. The action by classical
      probabilistic one-bit and deterministic two-bit gates such as NAND are
      implemented in terms of matrix operations and, as opposed to quantum computing,
      it is possible to copy bits. We present a way to explore this method of
      computation to solve search problems and count the number of solutions. We argue
      that if the classical computational cost of testing solutions (witnesses)
      requires less than O(n2) local two-bit gates acting on n bits, the search problem
      can be fully solved in subexponential time. Therefore, for this restricted type
      of search problem, the virtual parallelization scheme is faster than Grover's
      quantum algorithm.

PMID- 22861833
TI  - Inelastic multiple scattering of interacting bosons in weak random potentials.
AB  - We develop a diagrammatic scattering theory for interacting bosons in a three
      dimensional, weakly disordered potential. We show how collisional energy transfer
      between the bosons induces the thermalization of the inelastic single-particle
      current which, after only a few collision events, dominates over the elastic
      contribution described by the Gross-Pitaevskii ansatz.

PMID- 22861834
TI  - Spectra of sparse non-hermitian random matrices: an analytical solution.
AB  - We present the exact analytical expression for the spectrum of a sparse non
      hermitian random matrix ensemble, generalizing two standard results in random
      matrix theory: this analytical expression constitutes a non-hermitian version of
      the Kesten-McKay measure as well as a sparse realization of Girko's elliptic law.
      Our exact result opens new perspectives in the study of several physical problems
      modelled on sparse random graphs, which are locally treelike. In this context, we
      show analytically that the convergence rate of a transport process on a very
      sparse graph depends in a nonmonotonic way upon the degree of symmetry of the
      graph edges.

PMID- 22861835
TI  - Inner mechanics of three-dimensional black holes.
AB  - We investigate properties of the inner horizons of certain black holes in higher
      derivative three-dimensional gravity theories. We focus on Banados-Teitelboim
      Zanelli and spacelike warped anti-de Sitter black holes, as well as on
      asymptotically warped de Sitter solutions exhibiting both a cosmological and a
      black hole horizon. We verify that a first law is satisfied at the inner horizon,
      in agreement with the proposal of Castro and Rodriguez [arXiv:1204.1284]. We then
      show that, in topologically massive gravity, the product of the areas of the
      inner and outer horizons fails to be independent on the mass, and we trace this
      to the diffeomorphism anomaly of the theory.

PMID- 22861836
TI  - Odd tracks at hadron colliders.
AB  - New physics that exhibits irregular tracks such as kinks, intermittent hits, or
      decay in flight may easily be missed at hadron colliders. We demonstrate this by
      studying viable models of light, O(10  GeV), colored particles that decay
      predominantly inside the tracker. Such particles can be produced at staggering
      rates, and yet, may not be identified or triggered on at the LHC, unless
      specifically searched for. In addition, the models we study provide an
      explanation for the original measurement of the anomalous charged track
      distribution by CDF. The presence of irregular tracks in these models reconcile
      that measurement with the subsequent reanalysis and the null results of ATLAS and
      CMS. Our study clearly illustrates the need for a comprehensive study of
      irregular tracks at the LHC.

PMID- 22861837
TI  - Muon anomaly and dark parity violation.
AB  - The muon anomalous magnetic moment exhibits a 3.6sigma discrepancy between
      experiment and theory. One explanation requires the existence of a light vector
      boson, Z(d) (the dark Z), with mass 10-500 MeV that couples weakly to the
      electromagnetic current through kinetic mixing. Support for such a solution also
      comes from astrophysics conjectures regarding the utility of a U(1)(d) gauge
      symmetry in the dark matter sector. In that scenario, we show that mass mixing
      between the Z(d) and ordinary Z boson introduces a new source of "dark" parity
      violation, which is potentially observable in atomic and polarized electron
      scattering experiments. Restrictive bounds on the mixing (m(Z(d))/m(Z))delta are
      found from existing atomic parity violation results, delta2<2*10(-5). Combined
      with future planned and proposed polarized electron scattering experiments, a
      sensitivity of delta2~10(-6) is expected to be reached, thereby complementing
      direct searches for the Z(d) boson.

PMID- 22861841
TI  - Odd-particle systems in the shell model Monte Carlo method: circumventing a sign
      problem.
AB  - The shell model Monte Carlo method is a powerful technique to calculate thermal
      and ground-state properties of strongly correlated finite-size systems. However,
      its application to odd-particle-number systems has been hampered by the sign
      problem that originates from the projection on an odd number of particles. We
      circumvent this sign problem for the ground-state energy by extracting the ground
      state energy of the odd-particle-number system from the asymptotic behavior of
      the imaginary-time single-particle Green's function of the even-particle-number
      system. We apply this method to calculate pairing gaps of nuclei in the iron
      region. Our results are in good agreement with experimental pairing gaps.

PMID- 22861840
TI  - Evolution of shell structure in neutron-rich calcium isotopes.
AB  - We employ interactions from chiral effective field theory and compute the binding
      energies and low-lying excitations of calcium isotopes with the coupled-cluster
      method. Effects of three-nucleon forces are included phenomenologically as in
      medium two-nucleon interactions, and the coupling to the particle continuum is
      taken into account using a Berggren basis. The computed ground-state energies and
      the low-lying J(pi) = 2+ states for the isotopes (42,48,50,52)Ca are in good
      agreement with data, and we predict the excitation energy of the first J(pi) = 2+
      state in (54)Ca at 1.9 MeV, displaying only a weak subshell closure. In the odd
      mass nuclei (53,55,61)Ca we find that the positive parity states deviate strongly
      from the naive shell model.

PMID- 22861839
TI  - Precision mass measurements beyond 132Sn: anomalous behavior of odd-even
      staggering of binding energies.
AB  - Atomic masses of the neutron-rich isotopes (121-128)Cd, (129,131)In, (130-135)Sn,
      (131-136)Sb, and (132-140)Te have been measured with high precision (10 ppb)
      using the Penning-trap mass spectrometer JYFLTRAP. Among these, the masses of
      four r-process nuclei (135)Sn, (136)Sb, and (139,140)Te were measured for the
      first time. An empirical neutron pairing gap expressed as the odd-even staggering
      of isotopic masses shows a strong quenching across N = 82 for Sn, with a Z
      dependence that is unexplainable by the current theoretical models.

PMID- 22861842
TI  - Magnetic dipole moment of the doubly-closed-shell plus one proton nucleus 49Sc.
AB  - The nucleus 49Sc, having a single f(7/2) proton outside doubly magic 48Ca (Z=20,
      N=28), is one of the very few isotopes which makes possible testing of the
      fundamental theory of nuclear magnetism. The magnetic moment has been measured by
      online beta NMR of nuclei oriented at milli-Kelvin temperatures to be
      (+)5.616(25)  MU(N). The result is discussed in terms of a detailed theory of the
      structure of the magnetic moment operator, showing excellent agreement with
      calculated departure from the f(7/2) Schmidt limit extreme single-particle value.
      The measurement completes the sequence of moments of Sc isotopes with even
      numbers of f(7/2) neutrons: the first such isotopic chain between two major
      shells for which a full set of moment measurements exists. The result further
      completes the isotonic sequence of ground-state moments of nuclei with an odd
      number of f(7/2) protons coupled to a closed subshell of f(7/2) neutrons.
      Comparison with a recent shell-model calculation of the latter sequence is made.

PMID- 22861844
TI  - New precision mass measurements of neutron-rich calcium and potassium isotopes
      and three-nucleon forces.
AB  - We present precision Penning trap mass measurements of neutron-rich calcium and
      potassium isotopes in the vicinity of neutron number N=32. Using the TITAN
      system, the mass of 51K was measured for the first time, and the precision of the
      (51,52)Ca mass values were improved significantly. The new mass values show a
      dramatic increase of the binding energy compared to those reported in the atomic
      mass evaluation. In particular, 52Ca is more bound by 1.74 MeV, and the behavior
      with neutron number deviates substantially from the tabulated values. An
      increased binding was predicted recently based on calculations that include three
      nucleon (3N) forces. We present a comparison to improved calculations, which
      agree remarkably with the evolution of masses with neutron number, making neutron
      rich calcium isotopes an exciting region to probe 3N forces.

PMID- 22861843
TI  - Search for neutrinoless double-beta decay in 136Xe with EXO-200.
AB  - We report on a search for neutrinoless double-beta decay of 136Xe with EXO-200.
      No signal is observed for an exposure of 32.5 kg yr, with a background of
      ~1.5*10(-3)  kg(-1) yr(-1)  keV(-1) in the +/-1sigma region of interest. This
      sets a lower limit on the half-life of the neutrinoless double-beta decay
      T(1/2)(0nubetabeta)(136Xe)>1.6*10(25)  yr (90% C.L.), corresponding to effective
      Majorana masses of less than 140-380 meV, depending on the matrix element
      calculation.

PMID- 22861845
TI  - Laser-induced gas vortices.
AB  - Recently, several femtosecond-laser techniques have demonstrated molecular
      excitation to high rotational states with a preferred sense of rotation. We
      consider collisional relaxation in a dense gas of such unidirectionally rotating
      molecules, and suggest that due to angular momentum conservation, collisions lead
      to the generation of macroscopic vortex gas flows. This argument is supported
      using the Direct Simulation Monte Carlo method, followed by a computational gas
      dynamic analysis.

PMID- 22861846
TI  - Tomography of a high-purity narrowband photon from a transient atomic collective
      excitation.
AB  - We demonstrate efficient heralded generation of high purity narrow-bandwidth
      single photons from a transient collective spin excitation in a hot atomic vapor
      cell. Employing optical homodyne tomography, we fully reconstruct the density
      matrix of the generated photon and observe a Wigner function reaching the zero
      value without correcting for any inefficiencies. The narrow bandwidth of the
      photon produced is accompanied by a high generation rate yielding a high spectral
      brightness. The source is, therefore, compatible with atomic-based quantum
      memories as well as other applications in light-atom interfacing. This Letter
      paves the way to preparing and measuring arbitrary superposition states of
      collective atomic excitations.

PMID- 22861847
TI  - Extracting past-future vacuum correlations using circuit QED.
AB  - We propose a realistic circuit QED experiment to test the extraction of past
      future vacuum entanglement to a pair of superconducting qubits. The qubit P
      interacts with the quantum field along an open transmission line for an interval
      T(on) and then, after a time-lapse T(off), the qubit F starts interacting for a
      time T(on) in a symmetric fashion. After that, past-future quantum correlations
      will have transferred to the qubits, even if the qubits do not coexist at the
      same time. We show that this experiment can be realized with current technology
      and discuss its utility as a possible implementation of a quantum memory.

PMID- 22861848
TI  - Demonstration of a state-insensitive, compensated nanofiber trap.
AB  - We report the experimental realization of an optical trap that localizes single
      Cs atoms ?215  nm from the surface of a dielectric nanofiber. By operating at
      magic wavelengths for pairs of counterpropagating red- and blue-detuned trapping
      beams, differential scalar light shifts are eliminated, and vector shifts are
      suppressed by ~250. We thereby measure an absorption linewidth Gamma/2pi=5.7+/
      0.1  MHz for the Cs 6S(1/2), F=4->6P(3/2), F'=5 transition, where Gamma0/2pi=5.2 
      MHz in free space. An optical depth d?66 is observed, corresponding to an optical
      depth per atom d1?0.08. These advances provide an important capability for the
      implementation of functional quantum optical networks and precision atomic
      spectroscopy near dielectric surfaces.

PMID- 22861849
TI  - Coupling of nitrogen-vacancy centers to photonic crystal cavities in
      monocrystalline diamond.
AB  - The zero-phonon transition rate of a nitrogen-vacancy center is enhanced by a
      factor of ~70 by coupling to a photonic crystal resonator fabricated in
      monocrystalline diamond using standard semiconductor fabrication techniques.
      Photon correlation measurements on the spectrally filtered zero-phonon line show
      antibunching, a signature that the collected photoluminescence is emitted
      primarily by a single nitrogen-vacancy center. The linewidth of the coupled
      nitrogen-vacancy center and the spectral diffusion are characterized using high
      resolution photoluminescence and photoluminescence excitation spectroscopy.

PMID- 22861850
TI  - Dynamic Stark effect in strongly coupled microcavity exciton polaritons.
AB  - We present experimental observations of a nonresonant dynamic Stark shift in
      strongly coupled microcavity quantum well exciton polaritons--a system which
      provides a rich variety of solid-state collective phenomena. The Stark effect is
      demonstrated in a GaAs/AlGaAs system at 10 K by femtosecond pump-probe
      measurements, with the blueshift approaching the meV scale for a pump fluence of
      2  mJ cm(-2) and 50 meV red detuning, in good agreement with theory. The energy
      level structure of the strongly coupled polariton Rabi doublet remains unaffected
      by the blueshift. The demonstrated effect should allow generation of ultrafast
      density-independent potentials and imprinting well-defined phase profiles on
      polariton condensates, providing a powerful tool for manipulation of these
      condensates, similar to dipole potentials in cold-atom systems.

PMID- 22861851
TI  - Electrically driven nonreciprocity induced by interband photonic transition on a
      silicon chip.
AB  - We demonstrate electrically driven nonreciprocity on a silicon chip. By achieving
      an indirect interband photonic transition, we show that the transmission
      coefficients between two single-mode waveguides become dependent on the
      propagation directions only in the presence of the electrical drive. Our
      structure is characterized by a nonsymmetric scattering matrix identical to a
      linear magneto-optical device.

PMID- 22861852
TI  - PT-symmetric Talbot effects.
AB  - We show that complex PT-symmetric photonic lattices can lead to a new class of
      self-imaging Talbot effects. For this to occur, we find that the input field
      pattern has to respect specific periodicities dictated by the symmetries of the
      system. While at the spontaneous PT-symmetry breaking point the image revivals
      occur at Talbot lengths governed by the characteristics of the passive lattice,
      at the exact phase it depends on the gain and loss parameter, thus allowing one
      to control the imaging process.

PMID- 22861853
TI  - Taming random lasers through active spatial control of the pump.
AB  - Active control of the spatial pump profile is proposed to exercise control over
      random laser emission. We demonstrate numerically the selection of any desired
      lasing mode from the emission spectrum. An iterative optimization method is
      employed, first in the regime of strong scattering where modes are spatially
      localized and can be easily selected using local pumping. Remarkably, this method
      works efficiently even in the weakly scattering regime, where strong spatial
      overlap of the modes precludes spatial selectivity. A complex optimized pump
      profile is found, which selects the desired lasing mode at the expense of others,
      thus demonstrating the potential of pump shaping for robust and controllable
      single mode operation of a random laser.

PMID- 22861854
TI  - Largest Lyapunov exponents for lattices of interacting classical spins.
AB  - We investigate how generic the onset of chaos in interacting many-body classical
      systems is in the context of lattices of classical spins with nearest-neighbor
      anisotropic couplings. Seven large lattices in different spatial dimensions were
      considered. For each lattice, more than 2000 largest Lyapunov exponents for
      randomly sampled Hamiltonians were numerically computed. Our results strongly
      suggest the absence of integrable nearest-neighbor Hamiltonians for the infinite
      lattices except for the trivial Ising case. In the vicinity of the Ising case,
      the largest Lyapunov exponents exhibit a power-law growth, while further away
      they become rather weakly sensitive to the Hamiltonian anisotropy. We also
      provide an analytical derivation of these results.

PMID- 22861855
TI  - Spatial periodic forcing can displace patterns it is intended to control.
AB  - Spatial periodic forcing of pattern-forming systems is an important, but lightly
      studied, method of controlling patterns. It can be used to control the amplitude
      and wave number of one-dimensional periodic patterns, to stabilize unstable
      patterns, and to induce them below instability onset. We show that, although in
      one spatial dimension the forcing acts to reinforce the patterns, in two
      dimensions it acts to destabilize or displace them by inducing two-dimensional
      rectangular and oblique patterns.

PMID- 22861856
TI  - Structure of long-term average frequencies for Kuramoto oscillator systems.
AB  - We study the long-term average frequency as a function of the natural frequency
      for Kuramoto oscillators with periodic coefficients. Unlike the case for more
      general periodically forced oscillators, this function is never a "devil's
      staircase"; it may have plateaus at integer multiples of the forcing frequency,
      but we prove it is strictly increasing between these plateaus. The proof uses the
      fact that the flow maps for Kuramoto oscillators extend to Mobius transformations
      on the complex plane, and that Mobius transformations have particularly simple
      dynamics that rule out p:q mode locking except in the case of fixed points (q=1).
      We also give a criterion for the degeneration of an integer plateau to a single
      point and use it to explain the absence of plateaus at even multiples of the
      collective frequency for a Kuramoto system with a bimodal frequency distribution.

PMID- 22861857
TI  - Hydrodynamic synchronization of light driven microrotors.
AB  - Hydrodynamic synchronization is a fundamental physical phenomenon by which self
      sustained oscillators communicate through perturbations in the surrounding fluid
      and converge to a stable synchronized state. This is an important factor for the
      emergence of regular and coordinated patterns in the motions of cilia and
      flagella. When dealing with biological systems, however, it is always hard to
      disentangle internal signaling mechanisms from external purely physical
      couplings. We have used the combination of two-photon polymerization and
      holographic optical trapping to build a mesoscale model composed of chiral
      propellers rotated by radiation pressure. The two microrotors can be synchronized
      by hydrodynamic interactions alone although the relative torques have to be
      finely tuned. Dealing with a micron sized system we treat synchronization as a
      stochastic phenomenon and show that the phase lag between the two microrotors is
      distributed according to a stationary Fokker-Planck equation for an overdamped
      particle over a tilted periodic potential. Synchronized states correspond to
      minima in this potential whose locations are shown to depend critically on the
      detailed geometry of the propellers.

PMID- 22861858
TI  - Acoustic rotational manipulation using orbital angular momentum transfer.
AB  - We report on the first quantitative test of acoustic orbital angular momentum
      transfer to a sound absorbing object immersed in a viscous liquid. This is done
      by realizing an original experiment that is to spin a millimeter-size target disk
      using an ultrasonic vortex beam. We demonstrate the balance between the acoustic
      radiation torque calculated from the Brillouin stress tensor and the viscous
      torque evaluated from the steady state spinning frequency. Moreover, we unveil a
      rotational acoustic streaming phenomenon that results from the acoustic angular
      momentum transfer to the host fluid. We show that it lowers the viscous torque,
      thereby restoring the torque balance.

PMID- 22861859
TI  - Take off of small Leidenfrost droplets.
AB  - We put in evidence the unexpected behavior of Leidenfrost droplets at the later
      stage of their evaporation. We predict and observe that, below a critical size
      Rl, the droplets spontaneously take off due to the breakdown of the lubrication
      regime. We establish the theoretical relation between the droplet radius and its
      elevation. We predict that the vapor layer thickness increases when the droplets
      become smaller. A satisfactory agreement is found between the model and the
      experimental results performed on droplets of water and of ethanol.

PMID- 22861860
TI  - Observation of shot noise suppression at optical wavelengths in a relativistic
      electron beam.
AB  - Control of collective properties of relativistic particles is increasingly
      important in modern accelerators. In particular, shot noise affects accelerator
      performance by driving instabilities or by competing with coherent processes. We
      present experimental observations of shot noise suppression in a relativistic
      beam at the Linac Coherent Light Source. By adjusting the dispersive strength of
      a chicane, we observe a decrease in the optical transition radiation emitted from
      a downstream foil. We show agreement between the experimental results,
      theoretical models, and 3D particle simulations.

PMID- 22861861
TI  - Density fluctuation spectrum of solar wind turbulence between ion and electron
      scales.
AB  - We present a measurement of the spectral index of density fluctuations between
      ion and electron scales in solar wind turbulence using the EFI instrument on the
      ARTEMIS spacecraft. The mean spectral index at 1 AU was found to be -2.75+/-0.06,
      steeper than predictions for pure whistler or kinetic Alfven wave turbulence but
      consistent with previous magnetic field measurements. The steep spectra are also
      consistent with expectations of increased intermittency or damping of some of the
      turbulent energy over this range of scales. Neither the spectral index nor the
      flattening of the density spectra before ion scales were found to depend on the
      proximity to the pressure anisotropy instability thresholds, suggesting that they
      are features inherent to the turbulent cascade.

PMID- 22861862
TI  - "Ultracold" neutral plasmas at room temperature.
AB  - We report a measurement of the electron temperature in a plasma generated by a
      high-intensity laser focused into a jet of neon. The 15 eV electron temperature
      is determined using an analytic solution of the plasma equations assuming local
      thermodynamic equilibrium, initially developed for ultracold neutral plasmas. We
      show that this analysis method accurately reproduces more sophisticated plasma
      simulations in our temperature and density range. While our plasma temperatures
      are far outside the typical "ultracold" regime, the ion temperature is determined
      by the plasma density through disorder-induced heating just as in ultracold
      neutral plasma experiments. Based on our results, we outline a pathway for
      achieving a strongly coupled neutral laser-produced plasma that even more closely
      resembles ultracold neutral plasma conditions.

PMID- 22861863
TI  - Fractional resonances between waves and energetic particles in tokamak plasmas.
AB  - From numerical simulation and analytical modeling it is shown that fast ions can
      resonate with plasma waves at fractional values of the particle drift-orbit
      transit frequency when the plasma wave amplitude is sufficiently large. The
      fractional resonances, which are caused by a nonlinear interaction between the
      particle orbit and the wave, give rise to an increased density of resonances in
      phase space which reduces the threshold for stochastic transport. The effects of
      the fractional resonances on spatial and energy transport are illustrated for an
      energetic particle geodesic acoustic mode but they apply equally well to other
      types of MHD activity.

PMID- 22861864
TI  - Suppression of edge localized modes in high-confinement KSTAR plasmas by
      nonaxisymmetric magnetic perturbations.
AB  - Edge localized modes (ELMs) in high-confinement mode plasmas were completely
      suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations.
      Initially, the ELMs were intensified with a reduction of frequency, but
      completely suppressed later. The electron density had an initial 10% decrease
      followed by a gradual increase as ELMs were suppressed. Interesting phenomena
      such as a saturated evolution of edge T(e) and broadband changes of magnetic
      fluctuations were observed, suggesting the change of edge transport by the
      applied magnetic perturbations.

PMID- 22861865
TI  - Nonadiabatic preparation of spin crystals with ultracold polar molecules.
AB  - We study the growth dynamics of ordered structures of strongly interacting polar
      molecules in optical lattices. Using a dipole blockade of microwave excitations,
      we map the system onto an interacting spin-1/2 model possessing ground states
      with crystalline order, and describe a way to prepare these states by
      nonadiabatically driving the transitions between molecular rotational levels. The
      proposed technique bypasses the need to cross a phase transition and allows for
      the creation of ordered domains of considerably larger size compared to
      approaches relying on adiabatic preparation.

PMID- 22861866
TI  - Critical point coupling and proximity effects in 4He at the superfluid
      transition.
AB  - We report measurements of the superfluid fraction rho(s)/rho and specific heat
      c(p) near the superfluid transition of 4He when confined in an array of (2  MUm)3
      boxes at a separation of S=2  MUm and coupled through a 32.5 nm film. We find
      that c(p) is strongly enhanced when compared with data where coupling is not
      present. An analysis of this excess signal shows that it is proportional to the
      finite-size correlation length in the boxes xi(t,L), and it is measurable as far
      as S/xi~30-50. We obtain xi(0,L) and the scaling function (within a constant) for
      xi(t,L) in an L3 box geometry. Furthermore, we find that rho(s)/rho of the film
      persists a full decade closer to the bulk transition temperature T(lambda) than a
      film uninfluenced by proximity effects. This excess in rho(s)/rho is measurable
      even when S/xi>100, which cannot be understood on the basis of mean field theory.

PMID- 22861867
TI  - Eshelby twist and magic helical zinc oxide nanowires and nanotubes.
AB  - Twisted zinc oxide nanowires and nanotubes were recently synthesized by screw
      dislocation growth. We show theoretically that once their diameter increases
      above a critical size of the order of a few atomic spacings, the existence of
      these structures can be rationalized in terms of the energetics of surfaces and
      veritable Eshelby's twist linear elasticity mechanics supplemented by a nonlinear
      core term. For Burgers vector larger than the minimum allowed one, a twisted
      nanotube with well-defined thickness, rather than a nanowire, is the most stable
      nanostructure. Results are assistive for designing ultrathin nanostructures made
      out of nonlayered materials.

PMID- 22861868
TI  - Discovery of the ternary nanolaminated compound Nb2GeC by a systematic
      theoretical-experimental approach.
AB  - Since the advent of theoretical materials science some 60 years ago, there has
      been a drive to predict and design new materials in silicio. Mathematical
      optimization procedures to determine phase stability can be generally applicable
      to complex ternary or higher-order materials systems where the phase diagrams of
      the binary constituents are sufficiently known. Here, we employ a simplex
      optimization procedure to predict new compounds in the ternary Nb-Ge-C system.
      Our theoretical results show that the hypothetical Nb2GeC is stable, and excludes
      all reasonably conceivable competing hypothetical phases. We verify the existence
      of the Nb2GeC phase by thin film synthesis using magnetron sputtering. This
      hexagonal nanolaminated phase has a and c lattice parameters of ~3.24  A and
      12.82 A.

PMID- 22861869
TI  - Two-dimensional transition metal dichalcogenides under electron irradiation:
      defect production and doping.
AB  - Using first-principles atomistic simulations, we study the response of atomically
      thin layers of transition metal dichalcogenides (TMDs)--a new class of two
      dimensional inorganic materials with unique electronic properties--to electron
      irradiation. We calculate displacement threshold energies for atoms in 21
      different compounds and estimate the corresponding electron energies required to
      produce defects. For a representative structure of MoS2, we carry out high
      resolution transmission electron microscopy experiments and validate our
      theoretical predictions via observations of vacancy formation under exposure to
      an 80 keV electron beam. We further show that TMDs can be doped by filling the
      vacancies created by the electron beam with impurity atoms. Thereby, our results
      not only shed light on the radiation response of a system with reduced
      dimensionality, but also suggest new ways for engineering the electronic
      structure of TMDs.

PMID- 22861870
TI  - Freezing of water confined at the nanoscale.
AB  - Freezing of water in hydrophilic nanopores (D=1.2  nm) is probed at the
      microscopic scale using x-ray diffraction, Raman spectroscopy, and molecular
      simulation. A freezing scenario, which has not been observed previously, is
      reported; while the pore surface induces orientational order of water in contact
      with it, water does not crystallize at temperatures as low as 173 K.
      Crystallization at the surface is suppressed as the number of hydrogen bonds
      formed is insufficient (even when including hydrogen bonds with the surface),
      while crystallization in the pore center is hindered as the curvature prevents
      the formation of a network of tetrahedrally coordinated molecules. This sheds
      light on the concept of an ubiquitous unfreezable water layer by showing that the
      latter has a rigid (i.e., glassy) liquidlike structure, but can exhibit
      orientational order.

PMID- 22861871
TI  - Signature of a type-A glass transition and intrinsic confinement effects in a
      binary glass-forming system.
AB  - We study dynamically highly asymmetric binary mixtures comprised of small methyl
      tetrahydrofuran (MTHF) molecules and polystyrene. Combined use of dielectric
      spectroscopy, 2H nuclear magnetic resonance, incoherent quasielastic neutron
      scattering, and depolarized dynamic light scattering allows us to selectively
      probe the dynamics of the components in a broad dynamic range. It turns out that
      the mixtures exhibit two glass transitions in a wide concentration range although
      being fully miscible on a macroscopic scale. In between both glass transition
      temperatures, the dynamics of the small molecules show strong confinement
      effects, e.g., a crossover from Vogel-Fulcher to Arrhenius behavior of the time
      constants. Moreover, the dynamical behavior of small molecules close to the slow
      matrix is consistent with mode coupling theory predictions for a type-A glass
      transition, which was expected from recent theoretical and simulation studies in
      comparable systems.

PMID- 22861872
TI  - Dynamical flow arrest in confined gravity driven flows of soft jammed particles.
AB  - Using numerical simulations, we study the gravity driven flow of jammed soft
      disks in confined channels. We demonstrate that confinement results in increasing
      the yield threshold for the Poiseuille flow, in contrast to the planar Couette
      flow. By solving a nonlocal flow model for such systems, we show that this effect
      is due to the correlated dynamics responsible for flow, coupled with the stress
      heterogeneity imposed for the Poiseuille flow. We also observe that with
      increasing confinement, the cooperative nature of the flow results in increasing
      intermittent behavior. Our studies indicate that such features are generic
      properties of a wide variety of jammed materials.

PMID- 22861873
TI  - Finite-size scaling approach for critical wetting: rationalization in terms of a
      bulk transition with an order parameter exponent equal to zero.
AB  - Clarification of critical wetting with short-range forces by simulations has been
      hampered by the lack of accurate methods to locate where the transition occurs.
      We solve this problem by developing an anisotropic finite-size scaling approach
      and show that then the wetting transition is a "bulk" critical phenomenon with
      order parameter exponent equal to zero. For the Ising model in two dimensions,
      known exact results are straightforwardly reproduced. In three dimensions, it is
      shown that previous estimates for the location of the transition need revision,
      but the conclusions about a slow crossover away from mean-field behavior remain
      unaltered.

PMID- 22861874
TI  - Fundamental role of the H-bond interaction in the dissociation of NH3 on Si(001)
      (2*1).
AB  - Further insight into the dissociative adsorption of NH3 on Si(001) has been
      obtained using a combined computational and experimental approach. A novel route
      leading to the dissociation of the chemisorbed NH3 is proposed, based on H
      bonding interactions between the gas phase and the chemisorbed NH3 molecules. Our
      model, complemented by synchrotron radiation photoelectron spectroscopy
      measurements, demonstrates that the low temperature dissociation of molecular
      chemisorbed NH3 is driven by the continuous flux of ammonia molecules from the
      gas phase.

PMID- 22861875
TI  - Cyclotron resonance in the hidden-order phase of URu2Si2.
AB  - We report the first observation of cyclotron resonance in the hidden-order phase
      of ultraclean URu2Si2 crystals, which allows the full determination of angle
      dependent electron-mass structure of the main Fermi-surface sheets. We find an
      anomalous splitting of the sharpest resonance line under in-plane magnetic-field
      rotation. This is most naturally explained by the domain formation, which breaks
      the fourfold rotational symmetry of the underlying tetragonal lattice. The
      results reveal the emergence of an in-plane mass anisotropy with hot spots along
      the [110] direction, which can account for the anisotropic in-plane magnetic
      susceptibility reported recently. This is consistent with the "nematic" Fermi
      liquid state, in which itinerant electrons have unidirectional correlations.

PMID- 22861876
TI  - Exact density-functional potentials for time-dependent quasiparticles.
AB  - We calculate the exact Kohn-Sham potential that describes, within time-dependent
      density-functional theory, the propagation of an electron quasiparticle wave
      packet of nonzero crystal momentum added to a ground-state model semiconductor.
      The potential is observed to have a highly nonlocal functional dependence on the
      charge density, in both space and time, giving rise to features entirely lacking
      in local or adiabatic approximations. The dependence of the nonequilibrium part
      of the Kohn-Sham electric field on the local current and charge density is
      identified as a key element of the correct Kohn-Sham functional.

PMID- 22861877
TI  - Error analysis of free probability approximations to the density of states of
      disordered systems.
AB  - Theoretical studies of localization, anomalous diffusion and ergodicity breaking
      require solving the electronic structure of disordered systems. We use free
      probability to approximate the ensemble-averaged density of states without exact
      diagonalization. We present an error analysis that quantifies the accuracy using
      a generalized moment expansion, allowing us to distinguish between different
      approximations. We identify an approximation that is accurate to the eighth
      moment across all noise strengths, and contrast this with perturbation theory and
      isotropic entanglement theory.

PMID- 22861878
TI  - Nonlinear optical spin Hall effect and long-range spin transport in polariton
      lasers.
AB  - We report on the experimental observation of the nonlinear analogue of the
      optical spin Hall effect under highly nonresonant circularly polarized excitation
      of an exciton-polariton condensate in a GaAs/AlGaAs microcavity. The circularly
      polarized polariton condensates propagate over macroscopic distances, while the
      collective condensate spins coherently precess around an effective magnetic field
      in the sample plane performing up to four complete revolutions.

PMID- 22861879
TI  - Nonlinear conductance of long quantum wires at a conductance plateau transition:
      where does the voltage drop?
AB  - We calculate the linear and nonlinear conductance of spinless fermions in clean,
      long quantum wires, where short-ranged interactions lead locally to
      equilibration. Close to the quantum phase transition, where the conductance jumps
      from zero to one conductance quantum, the conductance obtains a universal form
      governed by the ratios of temperature, bias voltage, and gate voltage. Asymptotic
      analytic results are compared to solutions of a Boltzmann equation which includes
      the effects of three-particle scattering. Surprisingly, we find that for long
      wires the voltage predominantly drops close to one end of the quantum wire due to
      a thermoelectric effect.

PMID- 22861880
TI  - First-principles calculations of quasiparticle excitations of open-shell
      condensed matter systems.
AB  - We develop a Green's function approach to quasiparticle excitations of open-shell
      systems within the GW approximation. It is shown that accurate calculations of
      the characteristic multiplet structure require a precise knowledge of the self
      energy and, in particular, its poles. We achieve this by constructing the self
      energy from appropriately chosen mean-field theories on a fine frequency grid. We
      apply our method to a two-site Hubbard model, several molecules, and the
      negatively charged nitrogen-vacancy defect in diamond and obtain good agreement
      with experiment and other high-level theories.

PMID- 22861881
TI  - Boundary scattering in ballistic graphene.
AB  - We report magnetotransport measurements in ballistic graphene mesoscopic wires
      where the charge carrier mean free path is comparable to the wire width W.
      Magnetoresistance curves show characteristic peak structures where the peak field
      scales with the ratio of cyclotron radius R(c) and wire width W as W/R(c)=0.9+/
      0.1, due to diffusive boundary scattering. The obtained proportionality constant
      between R(c) and W differs from that of a classical semiconductor two-dimensional
      electron system in which W/R(c)=0.55.

PMID- 22861882
TI  - Observation of reentrant integer quantum Hall states in the lowest Landau level.
AB  - Measurements on very low disorder two-dimensional electrons confined to
      relatively wide GaAs quantum well samples with tunable density reveal a close
      competition between the electron liquid and solid phases near the Landau level
      filling factor nu=1. As the density is raised, the fractional quantum Hall liquid
      at nu=4/5 suddenly disappears at a well-width dependent critical density, and
      then reappears at higher densities with insulating phases on its flanks. These
      insulating phases exhibit reentrant nu=1 integer quantum Hall effects and signal
      the formation of electron Wigner crystal states. Qualitatively similar phenomena
      are seen near nu=6/5.

PMID- 22861883
TI  - Electron entanglement detected by quantum spin Hall systems.
AB  - We propose a promising electron entanglement detector consisting of two quantum
      spin Hall systems weakly coupled to a superconductor. The detection of electron
      spins along various polarization directions, which is a prerequisite for testing
      Bell's inequality on solid state spins, can be achieved in an all-electrical
      controlled manner utilizing the helical edge states. It is found that the
      violation of Bell's inequality exists in a large range of the tunneling
      parameters, which can be realized in mercury telluride quantum wells.

PMID- 22861884
TI  - Spin texture and circular dichroism in photoelectron spectroscopy from the
      topological insulator Bi2Te3: first-principles photoemission calculations.
AB  - By relativistic first-principles photoemission calculations for the topological
      insulator Bi2Te3, we study how the spin texture of the Dirac state manifests
      itself in circular dichroism. On one hand, there are significant modifications of
      the initial state's spin texture, which are explained by final-state effects and
      the symmetry of the photoemission setup. On the other hand, a highly symmetric
      setup allows us to draw conclusions about the detailed Dirac state's spin
      texture. Our study supports that circular dichroism in angular distribution
      successfully complements spin- and angle-resolved photoelectron spectroscopy from
      topological insulators.

PMID- 22861885
TI  - Fermi surface reconstruction by dynamic magnetic fluctuations.
AB  - We demonstrate that nearly critical quantum magnetic fluctuations in strongly
      correlated electron systems can change the Fermi surface topology and also lead
      to spin charge separation in two dimensions. To demonstrate these effects, we
      consider a small number of holes injected into the bilayer antiferromagnet. The
      system has a quantum critical point (QCP) which separates magnetically ordered
      and disordered phases. We demonstrate that in the physically interesting regime,
      there is a magnetically driven Lifshitz point (LP) inside the magnetically
      disordered phase. At the LP, the topology of the hole Fermi surface is changed.
      We also demonstrate that in this regime, the hole spin and charge necessarily
      separate when approaching the QCP. The considered model sheds light on generic
      problems concerning the physics of the cuprates.

PMID- 22861886
TI  - Evolution from unconventional spin density wave to superconductivity and a
      pseudogaplike phase in NaFe(1-x)Co(x)As.
AB  - We report the doping, temperature, and spatial evolutions of the electronic
      structure of NaFe(1-x)Co(x)As studied by scanning tunneling microscopy. In the
      parent state we directly observe the spin density wave gap, which exhibits
      unconventional features that are incompatible with simple Fermi surface nesting.
      The optimally doped sample has a single superconducting gap, but in the overdoped
      regime a novel pseudogaplike feature emerges. The pseudogaplike phase coexists
      with superconductivity in the ground state, persists well into the normal state,
      and shows strong spatial variations. The characteristics of the three distinct
      electronic states revealed here shed important new lights on the microscopic
      models for the iron-based superconductors.

PMID- 22861887
TI  - Three dimensionality and orbital characters of the Fermi surface in
      (Tl,Rb)(y)Fe(2-x)Se2.
AB  - We report a comprehensive angle-resolved photoemission spectroscopy study of the
      tridimensional electronic bands in the recently discovered Fe selenide
      superconductor ((Tl,Rb)(y)Fe(2-x)Se2 (T(c)=32  K). We determined the orbital
      characters and the k(z) dependence of the low energy electronic structure by
      tuning the polarization and the energy of the incident photons. We observed a
      small 3D electron Fermi surface pocket near the Brillouin zone center and a 2D
      like electron Fermi surface pocket near the zone boundary. The photon energy
      dependence, the polarization analysis and the local-density approximation
      calculations suggest a significant contribution from the Se 4p(z) and Fe 3d(xy)
      orbitals to the small electron pocket. We argue that the emergence of Se 4p(z)
      states might be the cause of the different magnetic properties between Fe
      chalcogenides and Fe pnictides.

PMID- 22861888
TI  - Cascade of magnetic field induced spin transitions in LaCoO3.
AB  - We present magnetization and magnetostriction studies of LaCoO3 in magnetic
      fields approaching 100 T. In contrast with expectations from single-ion models,
      the data reveal two distinct first-order transitions and well-defined
      magnetization plateaus. The magnetization at the higher plateau is only about
      half the saturation value expected for spin-1 Co3+ ions. These findings strongly
      suggest collective behavior induced by interactions between different electronic
      configurations of Co3+ ions. We propose a model that predicts crystalline spin
      textures and a cascade of four magnetic phase transitions at high fields, of
      which the first two account for the experimental data.

PMID- 22861889
TI  - Universal energy distribution of quasiparticles emitted in a local time-dependent
      quench.
AB  - We study the emission of quasiparticles in the scaling limit of the 1D quantum
      Ising chain at the critical point perturbed by a time-dependent local transverse
      field. We compute exactly and for a generic time dependence the average value of
      the transverse magnetization, its correlation functions, as well as the
      statistics of both the inclusive and exclusive work. We show that, except for a
      cyclic perturbation, the probability distribution of the work at low energies is
      a power law whose exponent is universal, i.e., does not depend on the specific
      time-dependent protocol, but only on the final value attained by the
      perturbation.

PMID- 22861890
TI  - Disorder strength and field-driven ground state domain formation in artificial
      spin ice: experiment, simulation, and theory.
AB  - Quenched disorder affects how nonequilibrium systems respond to driving. In the
      context of artificial spin ice, an athermal system comprised of geometrically
      frustrated classical Ising spins with a twofold degenerate ground state, we give
      experimental and numerical evidence of how such disorder washes out edge effects
      and provide an estimate of disorder strength in the experimental system. We prove
      analytically that a sequence of applied fields with fixed amplitude is unable to
      drive the system to its ground state from a saturated state. These results should
      be relevant for other systems where disorder does not change the nature of the
      ground state.

PMID- 22861891
TI  - Dimensionality driven spin-flop transition in layered iridates.
AB  - Using resonant x-ray diffraction, we observe an easy c-axis collinear
      antiferromagnetic structure for the bilayer Sr3Ir2O7, a significant contrast to
      the single layer Sr2IrO4 with in-plane canted moments. Based on a microscopic
      model Hamiltonian, we show that the observed spin-flop transition as a function
      of number of IrO2 layers is due to strong competition among intra- and interlayer
      bond-directional pseudodipolar interactions of the spin-orbit entangled
      J(eff)=1/2 moments. With this we unravel the origin of anisotropic exchange
      interactions in a Mott insulator in the strong spin-orbit coupling regime, which
      holds the key to the various types of unconventional magnetism proposed in 5d
      transition metal oxides.

PMID- 22861892
TI  - Nonadiabatic dynamics of two strongly coupled nanomechanical resonator modes.
AB  - The Landau-Zener transition is a fundamental concept for dynamical quantum
      systems and has been studied in numerous fields of physics. Here, we present a
      classical mechanical model system exhibiting analogous behavior using two
      inversely tunable, strongly coupled modes of the same nanomechanical beam
      resonator. In the adiabatic limit, the anticrossing between the two modes is
      observed and the coupling strength extracted. Sweeping an initialized mode across
      the coupling region allows mapping of the progression from diabatic to adiabatic
      transitions as a function of the sweep rate.

PMID- 22861893
TI  - Seebeck rectification enabled by intrinsic thermoelectrical coupling in magnetic
      tunneling junctions.
AB  - An intrinsic thermoelectric coupling effect in the linear response regime of
      magnetic tunneling junctions (MTJ) is reported. In the dc response, it leads to a
      nonlinear correction to Ohm's law. Dynamically, it enables a novel Seebeck
      rectification and second harmonic generation, which apply for a broad frequency
      range and can be magnetically controlled. A phenomenological model on the footing
      of the Onsager reciprocal relation and the principle of energy conservation
      explains very well the experimental results obtained from both dc and frequency
      dependent transport measurements performed up to GHz frequencies. Our work
      refines previous understanding of magnetotransport and microwave rectification in
      MTJs. It forms a new foundation for utilizing spin caloritronics in high
      frequency applications.

PMID- 22861894
TI  - Magnetic cycloid of BiFeO3 from atomistic simulations.
AB  - An effective Hamiltonian is developed to investigate the magnetic cycloid of the
      BiFeO3 (BFO) multiferroic. This approach reproduces many complex features of this
      cycloid, such as its plane of rotation containing the polarization and the newly
      discovered spin density waves resulting from the canting of magnetic dipoles out
      of this cycloidal plane. It also suggests that the energetic origin of the
      cycloid can be thought of in terms of the converse spin-current model, and
      reveals the mechanisms responsible for the spin density waves. Finally, this
      atomistic scheme resolves an ongoing controversy about the cycloid anharmonicity,
      and revisits a recent misconception about the relationship between out-of-plane
      spin-density waves and the weak magnetization associated with the spin-canted
      structure of BFO.

PMID- 22861895
TI  - Kapellasite: a kagome quantum spin liquid with competing interactions.
AB  - Magnetic susceptibility, NMR, muon spin relaxation, and inelastic neutron
      scattering measurements show that kapellasite, Cu3Zn(OH)6Cl2, a geometrically
      frustrated spin-1/2 kagome antiferromagnet polymorphic with herbertsmithite, is a
      gapless spin liquid showing unusual dynamic short-range correlations of
      noncoplanar cuboc2 type which persist down to 20 mK. The Hamiltonian is
      determined from a fit of a high-temperature series expansion to bulk
      susceptibility data and possesses competing exchange interactions. The magnetic
      specific heat calculated from these exchange couplings is in good agreement with
      experiment. The temperature dependence of the magnetic structure factor and the
      muon relaxation rate are calculated in a Schwinger-boson approach and compared to
      experimental results.

PMID- 22861896
TI  - High-resolution calorimetric study of Pb(Mg(1/3)Nb(2/3))O3 single crystal.
AB  - Motivated by the long-standing unresolved enigma of the relaxor ferroelectric
      ground state, we performed a high-resolution heat capacity and polarization study
      of the field-induced phase transition in the relaxor ferroelectric single crystal
      Pb(Mg(1/3)Nb(2/3))O3 (PMN) oriented along the [110] direction. We show that the
      discontinuous evolution of polarization as a function of the electric field or
      temperature is a consequence of a true first order transition from a glassy to
      ferroelectric state, which is accompanied by an excess heat capacity anomaly and
      released latent heat. We also find that in a zero field there is no ferroelectric
      phase transition in bulk PMN at any temperature, indicating that the nonergodic
      dipolar glass phase persists down to the lowest temperatures.

PMID- 22861897
TI  - Half-Heusler semiconductors as piezoelectrics.
AB  - We use a first-principles rational-design approach to demonstrate the potential
      of semiconducting half-Heusler compounds as a previously unrecognized class of
      piezoelectric materials. We perform a high-throughput scan of a large number of
      compounds, testing for insulating character and calculating structural,
      dielectric, and piezoelectric properties. Our results provide guidance for the
      experimental realization and characterization of high-performance materials in
      this class that may be suitable for practical applications.

PMID- 22861898
TI  - Observation of magnetic excitations of Skyrmion crystal in a helimagnetic
      insulator Cu2OSeO3.
AB  - We have investigated the low-energy dynamics of the triangular lattice of
      Skyrmions in a helimagnetic insulator Cu2OSeO3 in terms of microwave response. We
      have observed two elementary excitations of the Skyrmion with different
      polarization characteristics: the counterclockwise circulating mode at 1 GHz with
      the magnetic field polarization parallel to the Skyrmion plane and the breathing
      mode at 1.5 GHz with a perpendicular magnetic field polarization. These modes
      reflect the topological nature of Skyrmions and may play a central role in the
      Skyrmion dynamics.

PMID- 22861899
TI  - Elasticity of lyotropic chromonic liquid crystals probed by director
      reorientation in a magnetic field.
AB  - Using a magnetic Frederiks transition technique, we measure the temperature and
      concentration dependences of splay K1, twist K2, and bend K3 elastic constants
      for the lyotropic chromonic liquid crystal sunset yellow formed through
      noncovalent reversible aggregation of organic molecules in water. K1 and K3 are
      comparable to each other and are an order of magnitude higher than K2. At higher
      concentrations and lower temperatures, K1 and the ratios K1/K3 and K1/K2
      increase, which is attributed to elongation of self-assembled lyotropic chromonic
      liquid crystal aggregates, a feature not found in conventional thermotropic and
      lyotropic liquid crystals formed by covalently bound units of a fixed length.

PMID- 22861900
TI  - Surface energy as a barrier to creasing of elastomer films: an elastic analogy to
      classical nucleation.
AB  - In a soft elastic film compressed on a stiff substrate, creases nucleate at
      preexisting defects and grow across the surface of the film like channels. Both
      nucleation and growth are resisted by the surface energy, which we demonstrate by
      studying creases for elastomers immersed in several environments--air, water, and
      an aqueous surfactant solution. Measurement of the position where crease
      channeling is arrested on a gradient thickness film provides a uniquely
      characterized strain that quantitatively reveals the influence of surface energy,
      unlike the strain for nucleation, which is highly variable due to the sensitivity
      to defects. We find that these experimental data agree well with the prediction
      of a scaling analysis.

PMID- 22861901
TI  - Kinematics of the most efficient cilium.
AB  - In a variety of biological processes, eukaryotic cells use cilia to transport
      flow. Although cilia have a remarkably conserved internal molecular structure,
      experimental observations report very diverse kinematics. To address this
      diversity, we determine numerically the kinematics and energetics of the most
      efficient cilium. Specifically, we compute the time-periodic deformation of a
      wall-bound elastic filament leading to transport of a surrounding fluid at
      minimum energetic cost, where the cost is taken to be the positive work done by
      all internal molecular motors. The optimal kinematics are found to strongly
      depend on the cilium bending rigidity through a single dimensionless number, the
      Sperm number, and closely resemble the two-stroke ciliary beating pattern
      observed experimentally.

PMID- 22861902
TI  - Spontaneously broken neutral symmetry in an ecological system.
AB  - Spontaneous symmetry breaking plays a fundamental role in many areas of condensed
      matter and particle physics. A fundamental problem in ecology is the elucidation
      of the mechanisms responsible for biodiversity and stability. Neutral theory,
      which makes the simplifying assumption that all individuals (such as trees in a
      tropical forest)--regardless of the species they belong to--have the same
      prospect of reproduction, death, etc., yields gross patterns that are in accord
      with empirical data. We explore the possibility of birth and death rates that
      depend on the population density of species, treating the dynamics in a species
      symmetric manner. We demonstrate that dynamical evolution can lead to a
      stationary state characterized simultaneously by both biodiversity and
      spontaneously broken neutral symmetry.

PMID- 22861903
TI  - Ultrafast detonation of hydrazoic acid (HN3).
AB  - The fastest self-sustained chemical reactions in nature occur during detonation
      of energetic materials where reactions are thought to occur on nanosecond or
      longer time scales in carbon-containing materials. Here we perform the first
      atomistic simulation of an azide energetic material, HN3, from the beginning to
      the end of the chemical evolution and find that the time scale for complete
      decomposition is a mere 10 ps, orders of magnitude shorter than that of secondary
      explosives and approaching the fundamental limiting time scale for chemistry;
      i.e., vibrational time scale. We study several consequences of the short time
      scale including a state of vibrational disequilibrium induced by the fast
      transformations.

PMID- 22861904
TI  - Modulus, confinement, and temperature effects on surface capillary wave dynamics
      in bilayer polymer films near the glass transition.
AB  - We report relaxation times (tau) for surface capillary waves on 27-127 nm
      polystyrene (PS) top layers in bilayer films using x-ray photon correlation
      spectroscopy. At ~10  degrees C above the PS glass transition temperature (T(g)),
      tau tracks with underlayer modulus, being significantly smaller on softer
      substrates at low in-plane scattering wave vector. Relative to capillary wave
      theory, we also report stiffening behavior upon nanoconfinement of the PS layers.
      At PS T(g)+40  degrees C, both effects become negligible. We demonstrate how
      neighboring polymer domains impact dynamics over substantial length scales.

PMID- 22861905
TI  - Anchoring of drifting spiral and scroll waves to impermeable inclusions in
      excitable media.
AB  - Anchoring of spiral and scroll waves in excitable media has attracted
      considerable interest in the context of cardiac arrhythmias. Here, by bombarding
      inclusions with drifting spiral and scroll waves, we explore the forces exerted
      by inclusions onto an approaching spiral and derive the equations of motion
      governing spiral dynamics in the vicinity of inclusion. We demonstrate that these
      forces nonmonotonically depend on distance and can lead to complex behavior: (a)
      anchoring to small but circumnavigating larger inclusions; (b) chirality
      dependent anchoring.

PMID- 22861906
TI  - Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1.
AB  - AIM: To investigate the psychiatric and cognitive phenotype in young individuals
      with the childhood form of myotonic dystrophy type 1 (DM1). METHOD: Twenty-eight
      individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6,
      range 7-24y) were assessed using standardized instruments and cognitive testing
      of general intelligence, visual attention, and visual-spatial construction
      abilities. RESULTS: Nineteen patients had repeated a school grade. The mean (SD)
      Full-scale IQ was 73.6 (17.5) and mean Verbal IQ was significantly higher than
      the mean Performance IQ: 80.2 (19.22) versus 72.95 (15.58), p=0.01. Fifteen
      patients had one or more diagnoses on the DSM-IV axis 1, including internalizing
      disorders (phobia, n=7; mood disorder, n=6; other anxiety disorders, n=5) and
      attention-deficit-hyperactivity disorder, inattentive subtype (n=8). Twelve out
      of 22 patients had alexithymia (inability to express feelings with words and to
      recognize and share emotional states). Cognitive testing found severe impairments
      in visual attention and visual-spatial construction abilities in four out of 18,
      and 14 out of 24 patients respectively. No diagnosis was correlated with the
      transmitting parent's sex or with cytosine-thymine-guanine (CTG) repeat numbers.
      Patients with severe visual-spatial construction disabilities had a significantly
      longer CTG expansion size than those with normal visual-spatial abilities
      (p=0.04). INTERPRETATION: Children and adolescents with childhood DM1 have
      frequent diagnoses on DSM-IV axis 1, with internalizing disorders being the most
      common type of disorder. They also have borderline low intelligence and frequent
      impairments in attention and visual-spatial construction abilities.

PMID- 22861907
TI  - Online stable isotope analysis of dissolved organic carbon size classes using
      size exclusion chromatography coupled to an isotope ratio mass spectrometer.
AB  - Stable isotopic content of dissolved organic carbon (delta(13)C-DOC) provides
      valuable information on its origin and fate. In an attempt to get additional
      insights into DOC cycling, we developed a method for delta(13)C measurement of
      DOC size classes by coupling high-performance liquid chromatography (HPLC)-size
      exclusion chromatography (SEC) to online isotope ratio mass spectrometry (IRMS).
      This represents a significant methodological contribution to DOC research. The
      interface was evaluated using various organic compounds, thoroughly tested with
      soil-water from a C3-C4 vegetation change experiment, and also applied to
      riverine and marine DOC. delta(13)C analysis of standard compounds resulted in
      excellent analytical precision (<=0.30/00). Chromatography resolved soil DOC into
      3 fractions: high molecular weight (HMW; 0.4-10 kDa), low molecular weight (LMW;
      50-400 Da), and retained (R) fraction. Sample reproducibility for measurement of
      delta(13)C-DOC size classes was +/-0.250/00 for HMW fraction, +/- 0.540/00 for
      LMW fraction, and +/-1.30/00 for R fraction. The greater variance in delta(13)C
      values of the latter fractions was due to their lower concentrations. The limit
      of quantification (SD <=0.60/00) for each size fraction measured as a peak is 200
      ng C (2 mg C/L). delta(13)C-DOC values obtained in SEC mode correlated
      significantly with those obtained without column in the MUEA mode (p < 0.001,
      intercept 0.170/00), which rules out SEC-associated isotopic effects or DOC loss.
      In the vegetation change experiment, fractions revealed a clear trend in plant
      contribution to DOC; those in deeper soils and smaller size fractions had less
      plant material. It was also demonstrated that the technique can be successfully
      applied to marine and riverine DOC without further sample pretreatment.

PMID- 22862138
TI  - Cognitive, psychosocial, somatic and treatment factors predicting return to work
      after breast cancer treatment.
AB  - BACKGROUND: Breast cancer (BC) may affect the ability to work. In this study, we
      want to identify any associations between cognitive, psychosocial, somatic and
      treatment factors with time to return to work (RTW) among women treated for BC.
      METHODS AND PARTICIPANTS: At eight (baseline) and 11(follow-up) months after BC
      diagnosis, women who had received adjuvant treatment for early BC at Stockholm
      South General Hospital completed the Headminder neuropsychological tests to
      obtain the Cognitive Stability Index (CSI), the European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire and its Breast
      Cancer Module. At both time points, we compared the scores from women who had
      returned to work with those who had not. We also reviewed the medical
      certificates of women still on sick leave at 8, 11 and 18 months after diagnosis
      to determine why they had not returned to work. RESULTS: At baseline, 29 of 45
      enroled women were working and 15 were not (one dropped out after baseline
      testing). The 14 women still not working 11 months after BC diagnosis had more
      advanced BC (OR = 3.64, 95% CI 2.01-7.31), lymph-node involvement (OR = 18.80,
      95% CI 5.32-90.69) and Her 2-positive tumours (OR = 10.42,95% CI 2.19-65.32) than
      did working women. None of the scores for the four cognitive domains changed
      significantly at follow-up in either group. Comments on the medical certificates
      generally supported these findings. Independently of any adjuvant cancer therapy,
      overall quality of life improved and most women did RTW 18 months after BC
      diagnosis. CONCLUSIONS: Chemotherapy is associated with longer periods of sick
      leave. Cognitive functions do not predict RTW. Independently of any adjuvant
      therapy, most women eventually RTW in a few months. The ability to predict RTW
      after BC treatment should help prepare higher-risk patients for delayed RTW and
      allow earlier interventions to restore their social relations and quality of
      life.

PMID- 22862139
TI  - Helicobacter pylori and thrombocytopenia in the pregnant hispanic population.
AB  - OBJECTIVE: An association between Helicobacter pylori (H. pylori) and
      thrombocytopenia has been demonstrated in the literature in a non-pregnant
      population. The purpose of this study was to determine whether or not there is a
      similar association in the third trimester of pregnancy in a Hispanic population.
      METHODS: This is a secondary analysis of 82 pregnant Hispanic women with and
      without hyperemesis gravidarum who underwent serologic evaluation for H. pylori
      IgG. Results of complete blood counts obtained in the third trimester were
      analysed for thrombocytopenia. RESULTS: Of the 82 subjects who had H. pylori
      testing, 54 subjects had both serum H. pylori IgG results and third trimester
      platelet levels. The prevalence of thrombocytopenia was 11.1% (6/54). Thirty-six
      subjects were seropositive for H. pylori IgG and 18 subjects were seronegative.
      Of the 36 subjects who were H. pylori seropositive, four (11.1%) developed
      thrombocytopenia compared to three of 18 (16.7%) H. pylori seronegative subjects
      (P = 0.67). There was no difference between the groups in their mean platelet
      values (205 K/cu mm vs. 212 K/cu mm, P = 0.69). CONCLUSIONS: In this limited
      study, we found no association between H. pylori and thrombocytopenia in the
      pregnant Hispanic population.

PMID- 22862140
TI  - Small volume acid reflux in gastroesophageal reflux disease patients with hiatal
      hernia is only detectable by pH-metry but not by multichannel intraluminal
      impedance.
AB  - Until now, it is uncertain if the so-called pH-only reflux episodes that consist
      of a pH drop without evidence of retrograde bolus movement in multichannel
      intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal
      hernia (HH) may allow reflux of small volumes to occur that can be detected by pH
      metry but not by MII. The aim was to search for a mechanism that can explain pH
      only reflux, 20 patients (12 females and 8 males, median age 52 years,
      interquartile range [IQR]: 40.5-60.75 years) were investigated with MII-pH off
      PPI. Impedance and pH-metry data were analyzed separately. The differences in
      detection rate of acid reflux between pH-metry and MII were correlated with the
      presence of HH. In an in vitro experiment, MII-pH probes were flushed with citric
      acid in plastic tubes of different size with capillary diameter and diameters of
      2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six
      patients and absent in 14 patients. In patients with HH in comparison with
      patients with absent HH, the difference of acid reflux detection between pH-metry
      and MII is significantly higher (70%, IQR: 15-88% and 3.6%, IQR: 0-31%,
      respectively). In vitro all simulated reflux lead to a fall in pH whereas a
      corresponding decrease in impedance was only recognizable in the 4.5-mm plastic
      tubes. Acid reflux episodes in patients with HH are more frequently detected by
      pH-metry than by MII. Small volume reflux that does not lead to a decrease in
      impedance is the likely explanation for this phenomenon. 

PMID- 22862141
TI  - Post-mortem sperm retrieval in Australasia.
AB  - Post-mortem Sperm Retrieval (PMSR) is seldom requested in Australasia. The
      retrieval of sperm is permitted only by prior written consent or by order of the
      court. Sperm should be retrieved within 24 h following death; however, collection
      within 36 h may still be successful. The clinical response to such a request must
      be mindful of complex ethical and legal considerations. Clear, accessible and
      consistent law in this area would benefit medical, legal and societal
      stakeholders.

PMID- 22862142
TI  - gamma-Alumina: the essential and unexpected role of water for the structure,
      stability, and reactivity of "defect" sites.
AB  - Combining experiments and DFT calculations, we show that tricoordinate Al(III)
      Lewis acid sites, which are present as metastable species exclusively on the
      major (110) termination of gamma- and delta-Al(2)O(3) particles, correspond to
      the "defect" sites, which are held responsible for the unique properties of
      "activated" (thermally pretreated) alumina. These "defects" are, in fact, largely
      responsible for the adsorption of N(2) and the splitting of CH(4) and H(2). In
      contrast, five-coordinate Al surface sites of the minor (100) termination cannot
      account for the observed reactivity. The Al(III) sites, which are formed upon
      partial dehydroxylation of the surface (the optimal pretreatment temperature
      being 700  degrees C for all probes), can coordinate N(2) selectively. In
      combination with specific O atoms, they form extremely reactive Al,O Lewis acid
      base pairs that trigger the low-temperature heterolytic splitting of CH(4) and
      H(2) to yield Al-CH(3) and Al-H species, respectively. H(2) is found overall more
      reactive than CH(4) because of its higher acidity, hence it also reacts on four
      coordinate sites of the (110) termination. Water has the dual role of stabilizing
      the (110) termination and modifying (often increasing) both the Lewis acidity of
      the aluminum and the basicity of nearby oxygens, hence the high reactivity of
      partially dehyxdroxylated alumina surfaces. In addition, we demonstrate that the
      presence of water enhances the acidity of certain four-coordinate Al atoms, which
      leads to strong coordination of the CO molecule with a spectroscopic signature
      similar to that on Al(III) sites, thus showing the limits of this widely used
      probe for the acidity of oxides. Overall, the dual role of water translates into
      optimal water coverage, and this probably explains why in many catalyst
      preparations, optimal pretreatment temperatures are typically observed in the
      "activation" step of alumina.

PMID- 22862144
TI  - Molecular bases of the postzygotic barriers in interspecific crosses between the
      wild potato species Solanum acaule and Solanum commersonii.
AB  - To investigate the molecular bases of postzygotic hybridization barriers in tuber
      bearing Solanums, the wild species  Solanum commersonii  Dunal ex Poir. (cmm, 2n
      = 2x = 24, 1EBN) and  Solanum acaule  Bitter (acl, 2n = 4x = 48, 2EBN) were
      crossed in intra- and interspecific genotypic combinations, and the transcriptome
      of immature seeds was analyzed by using the cDNA-AFLP technique. From a total of
      423 analyzed cDNA fragments, 107 (25.3%) were differentially regulated in the
      compatible (acl * acl and cmm * cmm) versus incompatible (acl * cmm) crosses. DNA
      sequence data were obtained from 21 fragments and RT-PCR analyses were carried
      out with five fragments to validate the cDNA-AFLP differential pattern. Sequence
      analysis suggested a possible role for the differentially expressed sequences in
      cytokinesis, cell cycle, secondary and hormonal metabolism, biodegradation, and
      transport. In situ hybridization experiments with fragments encoding an ubiquitin
      fold modifier 1 precursor and a possible vesicle transport protein revealed
      expression of these genes in the embryo and endosperm. The results suggest that
      the collapse of the embryo and endosperm in incompatible crosses may be related
      to alterations in cell cycle and cytokinesis.

PMID- 22862143
TI  - Functional and morphological properties of pericytes in suburothelial venules of
      the mouse bladder.
AB  - BACKGROUND AND PURPOSE: In suburothelial venules of rat bladder, pericytes
      (perivascular cells) develop spontaneous Ca(2+) transients, which may drive the
      smooth muscle wall to generate spontaneous venular constrictions. We aimed to
      further explore the morphological and functional characteristics of pericytes in
      the mouse bladder. EXPERIMENTAL APPROACH: The morphological features of pericytes
      were investigated by electron microscopy and fluorescence immunohistochemistry.
      Changes in diameters of suburothelial venules were measured using video
      microscopy, while intracellular Ca(2+) dynamics were visualized using Fluo-4
      fluorescence Ca(2+) imaging. KEY RESULTS: A network of alpha-smooth muscle actin
      immunoreactive pericytes surrounded venules in the mouse bladder suburothelium.
      Scanning electron microscopy revealed that this network of stellate-shaped
      pericytes covered the venules, while transmission electron microscopy
      demonstrated that the venular wall consisted of endothelium and adjacent
      pericytes, lacking an intermediate smooth muscle layer. Pericytes exhibited
      spontaneous Ca(2+) transients, which were accompanied by phasic venular
      constrictions. Nicardipine (1 MUM) disrupted the synchrony of spontaneous Ca(2+)
      transients in pericytes and reduced their associated constrictions. Residual
      asynchronous Ca(2+) transients were suppressed by cyclopiazonic acid (10 MUM), 2
      aminoethoxydiphenyl borate (10 MUM), U-73122 (1 MUM), oligomycin (1 MUM) and
      SKF96365 (10 MUM), but unaffected by ryanodine (100 MUM) or YM-244769 (1 MUM),
      suggesting that pericyte Ca(2+) transients rely on Ca(2+) release from the
      endoplasmic reticulum via the InsP(3) receptor and also require Ca(2+) influx
      through store-operated Ca(2+) channels. CONCLUSIONS AND IMPLICATIONS: The
      pericytes in mouse bladder can generate spontaneous Ca(2+) transients and
      contractions, and thus have a fundamental role in promoting spontaneous
      constrictions of suburothelial venules.

PMID- 22862147
TI  - Excitation of plasmonic waves in graphene by guided-mode resonances.
AB  - We propose an active plasmonic device based on graphene. Highly confined
      plasmonic waves in monolayer graphene are efficiently excited using an etched
      diffractive grating on silicon. The guided-wave resonance of the combined
      structure creates a sharp notch on the normal-incidence transmission spectra, as
      the incident optical wave couples to the graphene plasmonic wave. This structure
      can be used as a highly tunable optical filter or a broad-band modulator because
      the resonant wavelength can be quickly tuned over a wide wavelength range by a
      small change in the Fermi energy level of the graphene. In this paper, we analyze
      the performance of this device with finite-difference time-domain simulations. We
      compare the proposed structure with recently demonstrated graphene nanoribbons
      based on bound plasmonic oscillations.

PMID- 22862148
TI  - Discovery and optimization of 1,3,4-trisubstituted-pyrazolone derivatives as
      novel, potent, and nonsteroidal farnesoid X receptor (FXR) selective antagonists.
AB  - LBVS of 12480 in-house compounds, followed by HTRF assay, resulted in one
      nonsteroidal compound (11) with antagonistic activity against FXR (69.01 +/-
      11.75 MUM). On the basis of 11, 26 new derivatives (12a-z) were designed and
      synthesized accordingly. Five derivatives (12f-g, 12p, 12u, and 12y) showed
      better antagonistic activities against FXR than compound 11. Remarkably, the most
      potent derivative, 12u (8.96 +/- 3.62 MUM), showed antagonistic capability
      approximately 10 times and 8-fold higher than that of the control (GS) and the
      starting compound 11, respectively. 12u was further confirmed to have high
      binding affinity with FXRalphaLBD, FXR specificity over six other nuclear
      receptors, and potent antagonistic activity against FXR in two cell testing
      platforms. 12u strongly suppressed the regulating effects of CDCA on FXR target
      genes. The therapeutic potential of 12u was identified by lowering the contents
      of triglyceride and cholesterol in human hepatoma HepG2 cells and in the
      cholesterol-fed C57BL/6 mices.

PMID- 22862149
TI  - Taste alteration and impact on quality of life after head and neck radiotherapy.
AB  - BACKGROUND: Dysgeusia is a relatively common complication of head and neck
      radiotherapy. The aim of this study was to evaluate taste condition after head
      and neck radiotherapy and its impact on quality of life. METHODS: In this cohort
      study 22 patients with head and neck cancer in Tehran University of Medical
      Sciences Hospital, were interviewed and examined before and 3 weeks after
      radiotherapy. Patients were given three consecutive concentrations of sugar,
      salt, citric acid and quinine sulfate solutions to evaluate their taste sensation
      by Whole Mouth Technique. EORTC-QLQ-H&N35 questionnaire was used before and after
      radiotherapy to assess the quality of life. Statistical analysis was done using
      Wilcoxon Signed Rank Test, Spearman's Coefficient of Correlation, Paired t-test,
      Multiple Ordinary and Multiple Linear Regressions. RESULTS: Significant changes
      were observed in concentrations and intensities of different perceived tastes
      before and after radiotherapy. All patients had dysgeusia after radiotherapy and
      72.2% had total taste loss. Impairment was observed mainly in salt and bitter
      tastes followed by sour and sweet. Subjective dysgeusia reported by 3/4 of the
      patients, which was correlated with objective taste disorder in terms of
      different tastes intensity. Age, sex, radiotherapy fractions, dosage and patients
      level of education had no significant effects on taste alteration. Quality of
      life was significantly deteriorated after the occurrence of dysgeusia in both
      total and partial taste losers. None of the aforementioned factors had
      significant effects on quality of life. CONCLUSION: Head and neck radiotherapy
      causes impairment in taste perception, and life quality is influenced by
      dysgeusia.

PMID- 22862150
TI  - Improved bovine ICSI outcomes by sperm selected after combined heparin
      glutathione treatment.
AB  - Despite widespread application of intracytoplasmic sperm injection (ICSI) in
      human-assisted reproductive techniques (ART), the efficiency of this method is
      still far from satisfactory in livestock, particularly in the bovine species with
      its unique sperm condensation. On the basis of the natural chemical structure of
      chromatin in condensed sperm, we developed a novel combined heparin-reduced
      glutathione (GSH) sperm pretreatment that improves the efficiency of bovine ICSI
      via selection of the most appropriate sperm at the time of ICSI. Assessment of
      sperm DNA integrity revealed that this pretreatment can be considered as a safe
      and efficient approach for in vitro sperm decondensation when compared to
      conventional sperm pretreatments with dithiothreitol (DTT). Injection of
      completely decondensed bull sperm derived from this pretreatment significantly
      improved fertilization and blastocyst formation rates compared to untreated or
      intact sperm injection (34.8 +/- 2.7 and 29.1 +/- 1.5 vs. 12.0 +/- 3.2 and 15.9
      +/- 1.2%, respectively; p<0.05). Real-time PCR analysis revealed that expression
      of pluripotent and anti-apoptosis markers in blastocysts derived by injection of
      completely decondensed sperm from heparin-GSH pretreatment were comparable to IVF
      when compared to the DTT pretreatment and control ICSI groups (p<0.05). The
      results of this study suggested that the degree of sperm decondensation derived
      from heparin-GSH pretreatment may affect ICSI efficiency in bovine.

PMID- 22862151
TI  - Correlation between left ventricular global and regional longitudinal systolic
      strain and impaired microcirculation in patients with acute myocardial
      infarction.
AB  - OBJECTIVES: We investigated the correlation between left ventricular global and
      regional longitudinal systolic strain (GLS and LRS) and coronary flow reserve
      (CFR) assessed by transthoracic echocardiography (TTE) in patients with a recent
      acute myocardial infarction (AMI). Furthermore, we investigated if LRS and GLS
      imaging is superior to conventional measures of left ventricle (LV) function.
      METHODS: In a consecutive population of first time AMI patients, who underwent
      successful revascularization, we performed comprehensive TTE. GLS and LRS were
      obtained from the three standard apical views. Assessment of CFR by TTE was
      performed in a modified apical view using color Doppler guidance. RESULTS: The
      study population consisted of 183 patients (51 females) with a median age of 63
      [54;70] years. Eighty-nine (49%) patients had a non-ST elevation myocardial
      infarction and 94 (51%) patients had a ST elevation myocardial infarction. The
      GLS was -15.2 [-19.3;-10.1]% in the total population of 183 patients. Total wall
      motion score index (WMSI) in the population was 1.19 [1;1.5]. Eighty-five
      patients suffered from culprit lesion in left anterior descending artery (LAD).
      The CFR in these patients was 1.86 [1.36;2.35] and the GLS was -14.3 [-18.9; 
      9.8]%. A significant difference was observed in the LRS in LAD territory in
      culprit LAD infarction patients with a CFR <= 2 (-9.6 [-13.77;-6.44]) compared
      with the LRS in LAD territory in culprit LAD infarction patients with a CFR > 2 (
      19.33 [-21.1;-16.5]), P < 0.0001. We found no significant difference between WMSI
      in LAD territory in culprit LAD infarction patients with a CFR <= 2 (1.56
      [1.06;2.23]) compared with WMSI in LAD territory in culprit LAD infarction
      patients with a CFR > 2 (1.37 [1.03;2.11]); P = 0.18. The same pattern was
      observed in both circumflex coronary artery (CX) and right coronary artery (RCA)
      territories. In the total population, we found a strong correlation between CFR
      and GLS (r = -0.85, P < 0.0001). This was also seen in the multivariate
      regression model adjusting for possible confounders including WMSI (P < 0.001).
      CONCLUSION: In this study, we have shown a close association between myocardial
      deformation in patients with a recent AMI and the degree of diminished
      microcirculation. We found that both GLS and LRS correlated with CFR. We conclude
      that GLS and LRS are significantly better tools to assess impaired CFR and LV
      function after a recent AMI, than conventional echocardiographic measurements.

PMID- 22862152
TI  - HLA-DQ association and allele competition in Chinese narcolepsy.
AB  - In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly
      associated with the DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype. Studies in
      African-Americans suggest a primary effect of DQB1*06:02, but this observation
      has been difficult to confirm in other populations because of high linkage
      disequilibrium between DRB1*15:01/3 and DQB1*06:02 in most populations. In this
      study, we studied human leucocyte antigen (HLA) class II in 202 Chinese
      narcolepsy patients (11% from South China) and found all patients to be
      DQB1*06:02 positive. Comparing cases with 103 unselected controls, and 110 and 79
      controls selected for the presence of DQB1*06:02 and DRB1*15:01, we found that
      the presence of DQB1*06:02 and not DRB1*15:01 was associated with narcolepsy. In
      particular, Southern Chinese haplotypes such as the DRB1*15:01-DQA1*01:02
      DQB1*06:01 and DRB1*15:01-DQA1*01:02-DQB1*05 were not associated with narcolepsy.
      As reported in Japanese, Koreans, African-Americans and Caucasians, additional
      protective effects of DQA1*01 (non-DQA1*01:02) and susceptibility effects of
      DQB1*03:01 were observed. These results illustrate the extraordinary conservation
      of HLA class II effects in narcolepsy across populations and show that DRB1*15:01
      has no effect on narcolepsy susceptibility in the absence of DQB1*06:02. The
      results are also in line with a previously proposed 'HLA-DQ allelic competition
      model' that involves competition between non-DQA1*01:02, non-DQB1*06:02
      'competent' (able to dimerize together) DQ1 alleles and the major DQalpha*01:02/
      DQbeta*06:02 narcolepsy heterodimer to reduce susceptibility.

PMID- 22862153
TI  - Recognizing myofascial pelvic pain in the female patient with chronic pelvic
      pain.
AB  - Myofascial pelvic pain (MFPP) is a major component of chronic pelvic pain (CPP)
      and often is not properly identified by health care providers. The hallmark
      diagnostic indicator of MFPP is myofascial trigger points in the pelvic floor
      musculature that refer pain to adjacent sites. Effective treatments are available
      to reduce MFPP, including myofascial trigger point release, biofeedback, and
      electrical stimulation. An interdisciplinary team is essential for identifying
      and successfully treating MFPP. 

PMID- 22862154
TI  - Initiation with menthol cigarettes and youth smoking uptake.
AB  - AIMS: We aimed to assess whether young people who first tried menthol cigarettes
      were at greater risk of becoming established smokers and dependent on nicotine
      than young people who started smoking non-menthol cigarettes. DESIGN: Cohort
      study using data from the American Legacy Longitudinal Tobacco Use Reduction
      Study (ALLTURS), a three-wave longitudinal school-based survey of middle school
      and high school students. Regression methods were used to assess the association
      between initiation with menthol cigarettes on risk of transitioning to
      established smoking or quitting from a non-smoking state at baseline and on
      nicotine dependence score at wave 3. SETTING: The study was conducted in 83
      schools in seven communities and five states in the United States. PARTICIPANTS:
      Analyses were restricted to youth who participated in all three waves of ALLTURS,
      were younger than age 17 at baseline, and had initiated smoking during waves 1 or
      2 of the study. MEASUREMENTS: Outcomes were indicators of a transition to
      established smoking or non-smoking from non-established smoking and a nicotine
      dependence score. The key explanatory variables were an indicator of initiation
      with menthol cigarettes and indicators for pattern of menthol use over time.
      FINDINGS: Initiating smoking with menthol cigarettes was associated with
      progression to established smoking [odds ratio (OR) = 1.80, confidence interval
      (CI): 1.02-3.16] and higher levels of nicotine dependence (beta = 1.25, CI: 0.1
      2.4). CONCLUSION: Young people in the United States who start smoking menthol
      cigarettes are at greater risk of progression to regular smoking and nicotine
      dependence than are young people who start smoking non-menthol cigarettes.

PMID- 22862155
TI  - Antidepressant up-titration: pharmacological and psychological considerations.
AB  - The use of antidepressant up-titration in starting therapies is useful in
      reducing side effects, but can induce delays in clinical response. Several
      aspects concerning slow or more aggressive titration have to be considered when
      using this strategy, such as pharmacological aspects (e.g., synaptic up
      regulation) and psychological/clinical aspects (e.g., adherence to antidepressant
      treatment, and the temperament and expectations of patients). Data from the
      literature are controversial, and so the choice between rapid and slow titration
      must be tailored more to the patient, rather than to the drug.

PMID- 22862156
TI  - Induction of respiratory immune responses in the chicken; implications for
      development of mucosal avian influenza virus vaccines.
AB  - The risk and the size of an outbreak of avian influenza virus (AIV) could be
      restricted by vaccination of poultry. A vaccine used for rapid intervention
      during an AIV outbreak should be safe, highly effective after a single
      administration and suitable for mass application. In the case of AIV, aerosol
      vaccination using live virus is not desirable because of its zoonotic potential
      and because of the risk for virus reassortment. The rational design of novel
      mucosal-inactivated vaccines against AIV requires a comprehensive knowledge of
      the structure and function of the lung-associated immune system in birds in order
      to target vaccines appropriately and to design efficient mucosal adjuvants. This
      review addresses our current understanding of the induction of respiratory immune
      responses in the chicken. Furthermore, possible mucosal vaccination strategies
      for AIV are highlighted.

PMID- 22862157
TI  - Neuroimaging in pregnancy: a review of clinical indications and obstetric
      outcomes.
AB  - OBJECTIVE: To determine indications and outcomes of pregnant women requiring
      neurologic imaging at a tertiary care center. METHODS: We reviewed medical
      records of women receiving magnetic resonance (MR) head imaging during pregnancy
      to determine indications for such imaging and their pregnancy outcomes. RESULTS:
      Between April 2007 and December 2008, 60 pregnant women presented to Brigham and
      Women's Hospital with severe headache or other acute neurologic complaint and
      underwent head imaging. Two patients were found to have significant findings
      considered to be neurologic emergencies: a right thalamic hemorrhage and a
      subarachnoid hemorrhage. Nine patients had abnormal findings not requiring
      immediate intervention but deeming further evaluation. Sixteen patients had
      abnormal findings determined to be incidental and unrelated to their indication
      for imaging. Thirty-three patients had unremarkable imaging studies. The most
      common presenting symptoms included headache (70%) and visual disturbances (48%).
      The most common imaging studies obtained were MR brain without contrast (87%) and
      MR angiography head without contrast (73%). The majority of patients (96%)
      delivered in the third trimester without significant complications. CONCLUSIONS:
      Most women who receive head imaging in pregnancy do not have adverse findings and
      have good obstetrical outcomes.

PMID- 22862158
TI  - Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis
      and comprehensive survey.
AB  - There have been many attempts at defining the electroencephalography (EEG)
      characteristics of nonconvulsive status epilepticus (NCSE) without a universally
      accepted definition. This lack of consensus arises because the EEG expression of
      NCSE does not exist in isolation, but reflects status epilepticus under the
      variety of pathologic conditions that occur with age, cerebral development,
      encephalopathy, and epilepsy syndrome. Current NCSE definitions include "boundary
      conditions," in which electroencephalographic seizure activity occurs without
      apparent clinical seizures. Furthermore, what appears to one interpreter as
      status epilepticus, is not to another reader, reflecting the "art" of EEG
      interpretation. Seizures and epilepsy syndromes have undergone an evolution that
      has moved beyond a classification of focal or generalized conditions into a
      syndromic approach. It seems appropriate to make similar changes in the EEG
      analysis of the syndromes of NCSE. In effect, the literature on epilepsy
      classification has progressed to incorporate the different NCSE types with
      clinical descriptions, but the specific EEG evidence for these types is found
      largely in individual reports, and often by description only. NCSE classification
      of EEG patterns should derive from the aggregate of published EEG patterns in the
      respective clinical subtype, supported by an analysis of these EEG studies. The
      analysis that follows presents clinical descriptions and EEG patterns of NCSE in
      the neonatal period, infancy, childhood, adulthood, and late adulthood from a
      syndromic perspective based on age, encephalopathy, cerebral development,
      etiology, and syndrome. Proceeding from the proposed classification of status
      epilepticus syndromes in "Status epilepticus: its clinical features and treatment
      in children and adults" (published in 1994 by Cambridge University Press, New
      York), we have performed a systematic search for reports presenting EEG patterns
      of NCSE using the online medical search engine PubMed for 22 different search
      strategies. EEG patterns were reviewed by two board-certified epileptologists who
      reached consensus regarding presence of NCSE. From a total of 4,328 search
      results, 123 cases with corresponding EEG patterns could be allocated to
      underlying epilepsy syndromes. Typical characteristic, prominent electrographic
      patterns, and sequential arrangements are elucidated for the different NCSE
      syndromes. This compendium of patterns by NCSE syndrome classification with
      illustration of EEGs, and delineation of electroencephalographic features helps
      define the characteristics and semiologic borderlines among the types of NCSE.

PMID- 22862159
TI  - An analysis of the survival rate after radiotherapy in lung cancer patients with
      bone metastasis: is there an optimal subgroup to be treated with high-dose
      radiation therapy?
AB  - We investigated the prognostic factors after radiotherapy for bone metastasis
      from lung cancer while taking the recent findings in the treatment of such cases
      into consideration. A total of 132 patients with bone metastases from
      pathologically confirmed lung cancer were evaluated regarding the following
      potential prognostic factors: treatment for primary site (surgery vs. other),
      treatment site (spine vs. other), number of bone metastases (solitary vs.
      multiple), number of metastatic organs (0 vs. 1 vs. >=2), neurological symptoms
      (no symptoms vs. numbness vs. paresis), degree of pain (no pain vs. mild pain vs.
      severe pain), performance status [PS] (0-1 vs. >=2), biological effective dose
      [BED] (>=40 Gy vs. <40Gy), time to distant metastasis (>=1 year vs. <1 year),
      histology (adenocarcinoma vs. others), and use of epidermal growth factor
      receptor [EGFR]-targeted agents (Yes vs. No). The univariate analysis
      demonstrated that all factors except for the treatment site were significant.
      Surgery as treatment for primary site, solitary bone metastasis, no visceral
      organ metastasis, no symptoms or numbness, no pain, PS<2, BED>=40 Gy, time to
      distant metastasis >= 1year, adenocarcinoma histology, and use of EGFR-targeted
      agents were correlated with a favorable prognosis. In a multivariate analysis,
      solitary bone metastasis, PS<2, BED>=40 Gy, adenocarcinoma histology, and the use
      of EGFR-targeted agents were significantly correlated with a better survival (p =
      0.038, 0.006, 0.003, 0.014, and <0.001, respectively). A contingency table to
      assess the relationship between each variable and the median survival time of the
      patients according to the administered BED showed that in patients with the time
      to distant metastasis >= 1year and the use of EGFR-targeted agents, the subgroups
      treated with BED>=40 Gy had a favorable prognosis. Our study suggests that high
      dose radiotherapy is associated with a better prognosis in combination with other
      favorable prognostic factors.

PMID- 22862160
TI  - Down-regulation of TCF21 is associated with poor survival in clear cell renal
      cell carcinoma.
AB  - Transcription factor 21 (TCF21) has been identified as a candidate tumor
      suppressor at 6q23-q24 that is epigenetically inactivated in many types of human
      cancers. We recently found that TCF21 methylation level was significantly
      increased in clear cell renal cell carcinoma (ccRCC). The purpose of this study
      was to investigate the prognostic impact of TCF21 expression in ccRCC and analyze
      the relationship between TCF21 expression and methylation level. We used real
      time PCR and immunohistochemical staining to detect the expression of TCF21, and
      used methylation specific-PCR (MS-PCR) to determine the methylation status of
      TCF21 in ccRCC samples and cell line 786-O. The results showed that TCF21
      expression level in ccRCC samples was significantly lower than in normal adjacent
      tissue samples (NAT samples). The Kaplan-Meier survival analysis demonstrated
      that TCF21 was a significant prognosticator of cancer-specific survival
      (p=0.001). Furthermore, the DNA demethylating agent 5'-azacytidine restored part
      of TCF21 expression by suppressing TCF21 methylation in 786-O. The methylation
      level of TCF21 in ccRCC samples was much higher than in NAT samples. These
      results suggest that the expression of TCF21 was an independent prognostic factor
      for poor survival in patients with ccRCC. Aberrant methylation was an important
      reason for the down-regulation the expression of TCF21, and may be associated
      with tumorigenesis in ccRCC.

PMID- 22862161
TI  - Roscovitine-induced apoptosis of H1299 cells depends on functional status of p53.
AB  - Roscovitine, an inhibitor of cyclin-dependent kinases, is promising anticancer
      agent. Its antiproliferative and cytotoxic effects can be mediated by the p53
      signaling pathway. To define the role of p53 in roscovitine-induced cell
      response, we prepared H1299/p53 cell lines inducibly expressing specific variants
      of p53 (p53wt and hotspot R175H, temperature-dependent P98A, A159V, S215G, Y220C,
      Y234C mutants). In the presence of roscovitine, each cell line variant behaved in
      specific way reflecting activity of the p53 protein. Roscovitine decreased
      production of the cell cycle inhibitor p21 and induced apoptosis. This effect was
      the most efficient in cells expressing p53wt protein with full activity. The cell
      expressing partially and conditionally active p53 mutants responded to
      roscovitine less efficiently. The cells expressing p53 mutants A159V and Y234C
      were very sensitive to roscovitine but their response was clearly temperature
      dependent. The cells expressing P98A, S215G and Y220C p53 mutants exhibited only
      weak sensitivity to roscovitine and underwent apoptosis in low frequency. In
      principle, each td p53 mutant responded to roscovitine in distinct way. We showed
      clearly that the impact of roscovitine on H1299 cells depends on functional
      status of p53 they produce. This suggests that patients with tumors exhibiting
      specific p53 variants can benefit from the roscovitine therapy.

PMID- 22862162
TI  - Total saponins of Tupistra chinensis induces apoptosis in A549 cells.
AB  - Tupistra chinensis Baker has been used as a folk remedy in China, and it has been
      shown to exhibit anti-inflammation, expectorant and anti-bacterial effects. In
      this study, we report the cytotoxic activity of the total saponins of Tupistra
      chinensis Baker (TST) against several carcinoma cell lines, including A549, MCF-7
      and HeLa cells with the IC50 values of 4.11 MUg/ml, 6.47 MUg/ml and 7.78 MUg/ml
      respectively. Treatment of A549 cells with TST resulted in growth inhibition and
      induction of apoptosis in a time-dependent manners determined by cell viability,
      chromatin condensation, DNA fragmentation and flow cytometry analysis. The
      activities of caspase-3, 9 were significantly increased following TST treatment.
      Real-time PCR analysis showed that the mRNA expression levels of pro-apoptosis
      related genes including Bax, P21, P27 and P53 were markedly increased in the
      cells treated with TST but anti-apoptosis related gene Bcl-2 was slightly
      decreased. TST also leads to a loss of mitochondrial membrane potential in a time
      dependent manner the release of cytochrome C from mitochondria into the cytosol.
      Thus, these results suggest that TST may play an important role in tumor growth
      suppression by inducing apoptosis in human A549 cells via mitochondria-dependent
      apoptotic pathways and the TST would be promising to treat human lung
      adenocarcinoma.

PMID- 22862163
TI  - CHEK2 gene alterations independently increase the risk of death from breast
      cancer in Bulgarian patients.
AB  - Checkpoint kinase 2 (CHEK2) is a DNA damage-activated protein kinase implicated
      in cell cycle checkpoint control. The significance of CHEK2 alterations for
      breast cancer incidence and clinical behavior is not clear. In this study we
      determined the mutational spectrum and the level of promoter hypermethylation of
      CHEK2 gene in a group of 145 Bulgarian patients with breast cancer. A special
      emphasis was put on the clinical impact of CHEK2 alterations for breast
      cancerogenesis. PCR-SSCP-sequencing analysis of the entire coding sequence of
      CHEK2 gene was performed to estimate the mutational profile of tumor samples.
      Methylation-sensitive SSCP was applied to determine the methylation status in CpG
      clusters implicated in CHEK2 silencing. Clinical significance of CHEK2
      alterations was evaluated using standard statistical methods. Mutations in CHEK2
      were identified in 9.65 % of the patients. Two novel missense substitutions
      Thr476Met (C >T) and Ala507Gly (C>G), and a novel silent variant Glu79Glu (A>G)
      were registered. However, hypermethylation was not found in any of the studied
      cases. Comparison with clinical characteristics showed that CHEK2 positive women
      have predominantly lobular type of breast carcinoma (r=0.04) and PR+ status
      (p=0.092). CHEK2 mutations correlated significantly with ATM+ status (p=0.046).
      All patients with the Glu79Glu variant were progesterone receptor positive
      (p=0.004). A decrease in overall survival (p = 0.6301) and a threefold increased
      independent risk of death (HR = 3.295, 95%CI 0.850-12.778, p = 0.085) in
      CHEK2+patients was found. Our data indicate the significance of CHEK2 gene
      alterations in contrast to promoter hypermethylation in breast cancerogenesis.
      Specificity of CHEK2 mutational profile for the Bulgarian population was found.
      Though CHEK2 mutational status correlated with more favorable clinical
      characteristics, including positive progesterone receptor and lobular
      histological type, it independently increased the risk of death in these
      patients.

PMID- 22862164
TI  - Single nucleotide polymorphisms in NOS2A and NOS3 genes are not associated with
      treatment response of non-small cell lung cancer patients following the
      definitive radiochemotherapy.
AB  - Nitric oxide (NO), is endogenously synthesized from L-arginine by nitric oxide
      synthase (NOS), exhibits a dual role in sensitivity to radiotherapy and
      chemotherapy of cancer cells. The aim of this study was to evaluate the influence
      of polymorphisms in NOS genes on treatment response of non-small-cell lung cancer
      (NSCLC) patients after radiochemotherapy. A cohort of 198 NSCLC patients treated
      with radiochemotherapy between 2009 and 2011 were included in this study.
      Genotyping analyses of 35 SNPs ( NOS2A, 21 and NOS3, 14) in each sample were
      conducted by using the Sequenom MassArray system. Unconditional logistic
      regression was performed to assess the association between treatment response and
      each genotype while adjusting or not for other covariates. Of 198 patients, 87
      (43.9%) had objective responses, and 111(56.1%) did not respond. We observed no
      significant associations between treatment response and each genotype. While
      adjusting for other covariates, the associations were also not significant. Our
      results suggest that genetic variations within the NOS2A and NOS3 genes may not
      influence the treatment response in NSCLC patients with radiochemotherapy. Future
      studies in this problem are required to confirm our findings.

PMID- 22862165
TI  - Prognostic effect of stromal myofibroblasts in lung adenocarcinoma.
AB  - Myofibroblasts are special cells with the features of both fibroblasts and smooth
      muscle cells, which are one of the most important cells in tumor stroma. The role
      of myofibroblasts in tumor stroma remains disputable. Some authors suggested that
      myofibroblasts can facilitate tumor progress, and another considered that
      myofibroblasts could prevent tumor cells diffusing. Bronchioloalveolar carcinoma
      (BAC) is a kind of adenocarcinoma in situ. With the destruction of the alveolar
      framework by tumor growth, BAC develops into mixed BAC and invasive
      adenocarcinoma, which is a natural model of transformation from carcinoma in situ
      to invasive carcinoma. In this study, the expression of myofibroblasts in BAC,
      mix-BAC and invasive adenocarcinoma was examined by immunohistochemical staining
      of surgical specimens from 102 patients. The results showed that positive
      expression of myofibroblasts in pure BAC (2/15, 13.33%) group was lower than in
      mix-BAC (17/38, 44.74%) and invasive adenocarcinoma (29/49, 59.18%) respectively,
      (p<0.05, p<0.01). In addition, myofibroblast positive expression was associated
      with lymph node metastasis, high stage, high grade, vascular invasion and
      shortened survival time in patients with lung adenocarcinoma. These data suggest
      that myofibroblasts are likely to facilitate the invasion and metastasis of the
      lung adenocarcinoma, and can be used as a prognostic marker. Myofibroblasts may
      become even a new target for treatment.

PMID- 22862166
TI  - Interdisciplinary treatment of glioblastoma: analysis of prognostic factors and
      treatment results in unselected patients.
AB  - Aim of the present study was to investigate survival rates of unselected patients
      with glioblastoma after multimodal treatment and estimation of prognostic
      factors. Data of 189 patients (118 men; 71 women; median age: 59 years) with
      histologically confirmed glioblastoma treated from 1999 to 2009 were analyzed
      retrospectively. Complete tumor resection was performed in 99 patients (52%),
      subtotal excision in 65 patients (34%), and stereotactic biopsy in 25 patients
      (13%). In 135 patients (71%), residual tumors were detectable in post-surgical
      imaging. All patients underwent three-dimensional conformal radiotherapy of the
      tumor region in shrinking-field technique to a total dose of 60 Gy. Beginning in
      2002, 124 patients (66%) received concomitant temozolomide (TMZ) treatment, 76
      patients among them were additionally treated with adjuvant TMZ. After disease
      progression, 74 patients underwent salvage therapy (salvage chemotherapy, n=61;
      local therapy, n=30). Actuarial 1- and 2- year progression-free survival (PFS)
      rates were 32% and 7%, overall survival (OS) rates were 54% and 22%,
      respectively. Without TMZ, 1- and 2- year OS rates were 47% and 11%, with
      concomitant TMZ 57% and 28%, and with concomitant and adjuvant TMZ 72% and 44%.
      In multivariate Cox proportional hazards regression models, age (p<0.001), extent
      of resection (p = 0.001), and TMZ (p < 0.001) were significantly associated with
      OS. Furthermore, a significant association between salvage therapy and improved
      survival was observed (p=0.020). RT with concomitant TMZ was well tolerated in
      the majority of patients and completed as scheduled in 78% of patients.
      Multimodal treatment including extensive surgical resection, radiotherapy and
      chemotherapy significantly improves prognosis of patients with glioblastoma and
      is feasible with acceptable toxicity in routine practice. To achieve optimal
      results, close coordination among all disciplines is required.

PMID- 22862167
TI  - Risk factors for invasive pulmonary fungal infection in patients with
      hematological malignancies not receiving hematopoietic stem cell transplant.
AB  - We investigated the incidence, pathogens and risk factors of invasive pulmonary
      fungal infection (IPFI) in patients with hematological malignancies who did not
      receive hematopoietic stem cell transplantation (HSCT). Of the 323 patients
      included, 106 had confirmed IPFI, 111 had pulmonary bacterial infections, and 106
      did not have pulmonary infections. The risk factors for IPFI were explored
      through logistic univariate and multivariate analysis. The incidence of IPFI in
      patients with hematological malignancies but without HSCT was 3.5%. The leading
      pathogen was Candida albicans which accounted for 50.7% of the infections, and
      the second one was Aspergillus which accounted for 37.3% of the infections. The
      main risk factors for these patients were days of hospitalization, history of
      IPFI, agranulocytosis, concomitant hypoproteinemia, number of antibiotics being
      used, concomitant bacterial sepsis, and age. Furthermore, Nystatin mouthwash was
      protective against IPFI. Among patients with hematological malignancies, IPFI
      causes the highest proportion of deaths. We have identified two important
      pathogens and several risk factors as well as one factor protective against IPFI.
      Awareness of risk factors and reduction of pathogens can decrease the incidence
      of IPFI.

PMID- 22862168
TI  - Enhanced chemosensitivity to CPT-11 in colorectal carcinoma xenografts  by small
      hairpin RNA interference targeting PLK1.
AB  - Commonly used drugs for the treatment of colon{} cancer patients like CPT-11
      shows severe side effects or induces resistance in clinical settings. Thus, we
      analyzed a combination of PLK1 (polo-like kinase 1)-specific short hair RNA
      (shRNA), a potent tool to destroy mitosis in cancer cells, together with CPT-11
      to enhance drug sensitivity. Cellular proliferation and apoptosis were determined
      in SW620 colorectal carcinoma cells. Knockdown of cellular PLK1 led to the
      decreased mRNA and PLK1 protein in RT-PCR and western blot assay. The viability
      declined (p<0.001) in MTT assay and colony formation assay, and the number of
      apoptotic cells was clearly increased (p<0.01) in flow cytometric analysis and
      Hoechst 33258 staining compared with control cells after incubation with PLK1
      specific shRNA and SN-38. We found the level of cleaved PARP was also increased
      in vitro. In vivo, employment of shRNA targeting PLK1 improved the sensitivity to
      treat SW620 nude mouse model toward CPT-11. The combination therapy inhibited
      cellular proliferation and promoted apoptosis observed at the percentage of PCNA
      and caspase3 by immunohistochemistry, accompanied with TUNEL assay. As we expect,
      the combination treatment delayed tumor growth (p<0.01) and simultaneously
      reduced tumor weight (p<0.01) compared with control group. Taken together,
      combination of PLK1-specific shRNA interference with low-dose CPT-11 triggered a
      antitumor efficacy and represented a potential strategy to treat colon cancer.

PMID- 22862169
TI  - Human lung cancer cell line SPC-A1 contains cells with characteristics of cancer
      stem cells.
AB  - Cancer stem cells (CSCs) play important roles in occurrence, development,
      recurrence and metastasis of cancer. Isolation and identification of CSCs have
      been performed from some cancer tissues or cells. In this paper, human lung
      adenocarcinoma stem cells were induced and isolated from SPC-A1 cells and their
      characteristics were determined. SPC-A1 cells were cultured in serum-free medium
      and epidermal growth factor and basic fibroblast growth factor were added into
      the medium to induce the formation of multicellular tumor spheroids. The results
      showed that floating multicellular tumor spheroids (named pulmospheres) were
      formed 5-10 d after the induction of SPC-A1 cells. Real-time PCR analysis showed
      that in the pulmospheres, the marker of bronchioalveolar stem cells, Clara cell
      secretary protein and the marker of AT2 cells, alveolar surfactant protein C were
      highly expressed. Furthermore, such embryonic stem cell markers as octamer
      binding transcription factor 4 (OCT-4), Bmi-1, and thyroid transcription factor 
      1 (TTF-1) were also highly expressed. Some miRNAs as hsa-miR-126, hsa-miR-145,
      hsa-let-7g, hsa-let-7d, hsa-let-7c, hsa-let-7e and hsa-miR-98, which were lowly
      expressed in SPC-A1 cells, were not expressed in the pulmospheres. Cell cycle
      analysis showed that 94.29 % of the pulmosphere cells were in G1 stages. Further
      study showed that these cells possessed higher proliferation and invasion
      activity than SPC-A1 cells. Tumorigenicity activity experiments on BALB/c nude
      mice showed that 1 * 103 of the pulmosphere cells could form tumors with similar
      pathological features with lung adenocarcinoma. In conclusion, lung
      adenocarcinoma stem cells were enriched in the pulmosphere cells and were with
      high tumorigenicity.

PMID- 22862170
TI  - TRAV gene expression in PBMCs and TILs in patients with breast cancer analyzed by
      a DNA melting curve (FQ-PCR) technique for TCR alpha chain CDR3 spectratyping.
AB  - PURPOSE: To explore the expression of the TRAV gene in peripheral blood
      mononuclear cells (PBMCs) and in tumor-infiltrating lymphocytes (TILs) in the
      patients with breast cancer using a DNA melting curve (FQ-PCR) technique for T
      cell receptor (TCR) alpha chain CDR3 spectratyping. Peripheral blood samples and
      tissue samples were obtained from thirty breast cancer patients. Total RNA was
      extracted from PBMCs and tumor tissues and then reverse transcribed into cDNA. FQ
      PCR was used to amplify the human TCR alpha chain CDR3 region with the primers to
      the TRAV and TRAC genes. TCR alpha chain CDR3 spectratyping and partial CDR3
      sequencing were used to determine use of TRAV gene product in T cell responses.
      TCR alpha CDR3 spectratyping showed preferential usage of certain TRAV genes in
      the PBMCs and TILs of all patients with breast cancer. The frequencies of
      TRAV1.1, TRAV9, and TRAV29 exceeded 30% in PBMCs and the frequencies of TRAV1.1
      and TRAV22 exceeded 30% in TILs. More than three quarters of the patients (23/30)
      overexpressed the same gene in both PBMCs and TILs; for example, patient-1 highly
      expressed TRAV9 in the PBMCs and TILs. Patients with positive or negative tumor
      markers of estrogen receptor (ER), progesterone receptor (PR), pS2, C-erbB-2,
      nm23, P53, and Ki-67 showed no significant common TRAV gene expression, but some
      TRAV gene preferential usage frequencies exceeded 20%. For example, five of seven
      patients positive for ER had high levels of expression of TRAV1.1 and TRAV3.
      Finally, the amino acid sequence of TCR CDR3 region showed some common motifs in
      some of the patients. CONCLUSIONS: TRAV gene expression was complex and diverse
      in the patients with breast cancer. The TRAV gene usage may be closely related to
      the diversity of breast tumor antigens and the differential immune responses
      observed in individual patients. Research into the immunological mechanism of T
      cells may provide guidance for individual T cell-directed therapy for breast
      cancer.

PMID- 22862171
TI  - The dynamics of cancer stem cells.
AB  - With the formulation of the hierarchical model of tumor cell organization, cancer
      stem cells came to the forefront of cancer biology. As the only self-renewing
      tumor cells, they were made responsible for continuous tumor growth and their
      intrinsic self-protection ability was postulated to underlie cancer therapy
      resistance and/or recurrence. The concept of migrating cancer stem cells extended
      the relevance of the hierarchical cancer cell model to issue of cancer
      progression, with the crucial experimental evidence being provided by the
      demonstration that epithelial mesenchymal transition can convey stemness.
      Accordingly, cancer stem cells probably represent a highly dynamic cell
      population continuously differentiating and being continuously replenished by
      processes like mesenchymal epithelial transition and epithelial mesenchymal
      transition, respectively. Consequently, from the point of view of therapeutic
      targeting, cancer stem cells obviously do not represent a fixed target population
      any longer. Understanding the dynamic nature of cancer stem cells is thus
      essential not only for the progress in our understanding of basic cancer biology,
      but also from the therapeutic perspective.

PMID- 22862172
TI  - Signal transduction pathways participating in homeostasis and malignant
      transformation of the intestinal tissue.
AB  - Intestinal homeostasis is a complex and tightly regulated process governed by a
      variety of signalling pathways that balance cell proliferation and
      differentiation. As revealed by extensive use of defined mouse models,
      perturbations within the signalling circuitry trigger initial expansion of
      premalignant cells. In this review, we attempt to summarise recent advances in
      the knowledge of the cellular signalling mechanisms that drive tumorigenesis in
      the human and mouse intestine.

PMID- 22862173
TI  - Fibroblast-dependent regulation of the stem cell properties of cancer cells.
AB  - There is emerging evidence that cancer stem cells (CSCs), like normal tissue stem
      cells, are regulated by a niche formed of mesenchymal cells. In this review we
      summarize the current knowledge of the role of cancer associated fibroblasts
      (CAFs) in a tentative CSC niche. We also discuss findings from our own studies
      showing that CAF derived factors have a strong stimulatory effect on the stem
      cell properties of breast cancer cells. Based on recent literature we conclude
      that CAFs are strong modulators of the stem cell properties of cancer cells. This
      effect is likely to be particularly relevant under circumstances of early stages
      of tumor cell dissemination and metastasis.

PMID- 22862174
TI  - Stem cells in the biology of normal urothelium and urothelial carcinoma.
AB  - Urothelium is a special type of stratified epithelium that lines the distal
      portion of the urinary tract. For a long time, basal urothelial cells have been
      suspected to include a population of urothelial stem cells. Recent experiments
      identifying label-retaining cells as well as lineage tracing analyses corroborate
      this notion. There are striking morphological and antigenic similarities between
      basal or differentiated urothelial cells and the corresponding cells in some
      urothelial carcinomas. In this respect, basal cell-specific markers provide good
      candidates to identify urothelial carcinoma stem cells, e.g. specific
      cytokeratins (CK5, CK14, CK17) or adhesion molecules (specific integrin
      subspecies, CD44). Common properties of the stem cells of normal urothelium and
      urothelial cancer have thus emerged. Both are characterized by a remarkable
      plasticity and both rely on reciprocal interactions with stromal fibroblasts.
      However, the stem cells of individual urothelial carcinomas appear to differ
      considerably and may contribute to the heterogeneity of this disease. The
      presence, quantity, and particular biological nature of urothelial carcinoma stem
      cells in each case may thus carry important clinical information that might allow
      a rationale stratification of urothelial cancer patients for treatment in the
      near future.

PMID- 22862175
TI  - Neuroblastoma stem cells - mechanisms of chemoresistance and histone deacetylase
      inhibitors.
AB  - Cancer stem cells (CSCs) form a small proportion of tumor cells that have stem
      cell properties: self-renewal capacity, the ability to develop into different
      lineages and proliferative potential. The interest in CSCs emerged from their
      expected role in initiation, progression and recurrence of many tumors. They are
      generally resistant to conventional chemotherapy and radiotherapy. There are two
      hypotheses about their origin: The first assumes that CSCs may arise from normal
      stem cells, and the second supposes that differentiated cells acquire the
      properties of CSCs. Both hypotheses are not mutually exclusive, as it is possible
      that CSCs have a diverse origin in different tumors. CD133+ cells (CD133 is
      marker of CSC in some tumors) isolated from NBL, osteosarcoma and Ewing sarcoma
      cell lines are resistant to cisplatin, carboplatin, etoposide and doxorubicin
      than the CD133- ones. Being resistant to chemotherapy, there were many attempts
      to target CSCs epigenetically including the use of histone deacetylase
      inhibitors. The diverse influence of valproic acid (histone deacetylase
      inhibitor) on normal and cancer stem cells was proved in different experiments.
      We have found an increase percentage of CD133+ NBL cells after their incubation
      with VPA in a dose that does not induce apoptosis. Further researches on CSCs and
      clinical application for their detection are necessary: (i) to define the CSC
      function in carcinogenesis, cancer development and their role in metastasis; (ii)
      to find a specific marker for CSCs in different tumors; (iii) to explain the role
      of different pathways that determine their behavior and (iv) to explain
      mechanisms of chemoresistance of CSCs.

PMID- 22862176
TI  - Ovarian cancer stem cells.
AB  - Because of its semi-solid character in dissemination and growth, advanced ovarian
      cancer with its hundreds of peritoneal tumor nodules and plaques appears to be an
      excellent in vivo model for studying the cancer stem cell hypothesis. The most
      important obstacle, however, is to adequately define and isolate these tumor
      initiating cells endowed with the properties of anoikis-resistance and unlimited
      self-renewal. Until now, no universal single marker or marker constellation has
      been found to faithfully isolate (ovarian) cancer stem cells. As these
      multipotent cells are known to possess highly elaborated efflux systems for
      cytotoxic agents, these pump systems have been exploited to outline putative stem
      cells as a side-population (SP) via dye exclusion analysis. Furthermore, the
      cells in question have been isolated via flow cytometry on the basis of cell
      surface markers thought to be characteristic for stem cells.In the Vienna variant
      of the ovarian cancer cell line A2780 a proof-of-principle model with both a
      stable SP and a stable ALDH1A1+ cell population was established. Double staining
      clearly revealed that both cell fractions were not identical. Of note, A2780V
      cells were negative for expression of surface markers CD44 and CD117 (c-kit).
      When cultured on monolayers of healthy human mesothelial cells, green
      fluorescence-protein (GFP)-transfected SP of A2780V exhibited spheroid-formation,
      whereas non-side-population (NSP) developed a spare monolayer growing over the
      healthy mesothelium. Furthermore, A2780V SP was found to be partially resistant
      to platinum. However, this resistance could not be explained by over-expression
      of the "excision repair cross-complementation group 1" (ERCC1) gene, which is
      essentially involved in the repair of platinated DNA damage. ERCC1 was,
      nonetheless, over-expressed in A2780V cells grown as spheres under stem cell
      selective conditions as compared to adherent monolayers cultured under
      differentiating conditions. The same was true for the primary ovarian cancer
      cells B-57.In summary our investigations indicate that even in multi-passaged
      cancer cell lines hierarchic government of growth and differentiation is
      conserved and that the key cancer stem cell population may be composed of small
      overlapping cell fractions defined by various arbitrary markers.

PMID- 22862177
TI  - Stem cell based glioblastoma gene therapy.
AB  - There is no curative therapy for glioblastoma multiforme (GBM) thus far. Combined
      therapies including surgery, followed by concomitant irradiation and chemotherapy
      with the DNA alkylating agent temozolomide (TMZ), slightly improves patients'
      survival but the prognosis remains poor. The fatal nature of glioblastoma is
      caused by tumor-initiating glioblastoma cells. The tumor tropic ability of adult
      mesenchymal stem cells offers the attractive possibility to use these cells as a
      vehicle to deliver therapeutic agents to the site of the tumor. In preclinical
      studies using animal models, mesenchymal stem cells engineered to express suicide
      genes were shown to elicit a significant antitumor response against various
      tumors including glioblastoma. This review summarizes the current state of
      knowledge about stem cell directed glioblastoma therapy. Results obtained in a
      preclinical study using mesenchymal stem cells engineered to express cytosine
      deaminase provided evidence that stem cell based gene therapy might also attack
      glioblastoma stem cells and therefore be curative. In addition to stem cell
      directed prodrug gene therapies, other immunotherapeutic modalities using
      mesenchymal stem cells are discussed as well. Encouraging results of preclinical
      studies of stem cell based gene therapy for glioblastoma support the argument to
      begin clinical studies.

PMID- 22862178
TI  - Novel nonclassical antifolate, 2-[N-(2'-Hydroxyethyl)amino]methyl-3H-quinazolin-4
      one, with a potent antineoplastic activity toward leukemia cells.
AB  - This study was aimed to investigate the therapeutic potential of novel
      nonclassical antifolate, 2-[N-(2'-Hydroxyethyl)ami-no]methyl-3H-quinazolin-4-one
      (HEAMQ), toward human promonocytic U937 and murine lymphoblastic L1210 cell
      lines. The antiproliferative activity of HEAMQ was determined by MTT assay and
      its effects on cell cycle progression and apoptosis were studied by flow
      cytometry, and by immunoblots, respectively. In addition, combination
      chemotherapy of HEAMQ with cisplatin and temozolomide under in vitro and in vivo
      conditions was tested. HEAMQ showed concentration- and time-dependent
      cytotoxicity toward U937 and L1210 cells. It induced G2/M arrest that in U937
      cells was associated with a marked decrease in the protein expressions of cyclin
      A, cyclin B, and cyclin-dependent kinase Cdk1. HEAMQ-induced apoptosis was
      accompanied with up-regulation of the protein expression of Bax and down
      regulation of the protein expression of Bcl-2, Mcl-1, XIAP, and survivin,
      resulting in cytochrome c release and activation of caspases. Inhibitors of JNK
      (SP600125) and p38 MAPK (SB203580) suppressed HEAMQ-induced apoptosis and G2/M
      phase arrest, attenuated the activation of Bax, and blocked down-regulation of
      Bcl-2, XIAP and survivin in HEAMQ-treated U937 cells. In addition, combinations
      of HEAMQ with cisplatin and temozolomide resulted in synergistic inhibition of
      cell growth, producing long-term survivors of L1210 tumor-bearing mice. In
      conclusion, these results indicate that HEAMQ antineoplastic activity toward
      leukemia cells is associated with cell cycle arrest and apoptosis. The in vivo
      studies further confirmed the antitumor activity of HEAMQ and highlighted that
      this agent could be used to further increase therapeutic efficacies of
      traditional chemotherapeutic agents.

PMID- 22862179
TI  - Association of perfluorooctanoic acid with HDL cholesterol and circulating miR
      26b and miR-199-3p in workers of a fluorochemical plant and nearby residents.
AB  - Perfluoroalkyl chemicals (PFCs) are stable man-made compounds with many
      industrial and commercial uses. Concern has been raised that they may exert
      deleterious effects, especially on lipid regulation. We aimed to assess exposure
      to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and seven
      other PFCs in occupational workers from a fluorochemical plant and nearby
      community residents, and to investigate the association between PFOA and serum
      biomarkers. Serum biomarkers included not only biochemical parameters, such as
      lipids and enzymes, but also circulating microRNAs (miRNAs). Samples were
      analyzed by high-pressure liquid chromatography/tandem mass spectrometry (HPLC
      MS/MS). Circulating miRNA levels were detected by quantitative polymerase chain
      reaction (PCR). Analyses were conducted by correlation and linear regression. We
      detected PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid
      (PFNA), and perfluorodecanoic acid (PFDA) in all samples. The median levels of
      serum PFOA and PFOS were 284.34 ng/mL and 34.16 ng/mL in residents and 1635.96
      ng/mL and 33.46 ng/mL in occupational participants, respectively. To our
      knowledge, we found for the first time that PFOA was negatively associated with
      high-density lipoprotein cholesterol (HDL-C) in workers using linear regression
      after adjusting for potential confounders. Circulating miR-26b and miR-199a-3p
      were elevated with serum concentration of PFOA. Although the limitations of small
      sample size and the cross-sectional nature of the current study constrained
      causal inferences, the observed associations between PFOA and these serum
      biomarkers warrant further study.

PMID- 22862180
TI  - How can proteins enter the interior of a MOF? Investigation of cytochrome c
      translocation into a MOF consisting of mesoporous cages with microporous windows.
AB  - It has been demonstrated for the first time that the heme protein cytochrome c
      (Cyt c) can enter the interior of a MOF despite the larger molecular dimension of
      the protein relative to the access pore sizes. Mechanistic studies suggest that
      the Cyt c molecules must undergo a significant conformational change during
      translocation into the MOF interior through the relatively small nanopores.

PMID- 22862285
TI  - Trends and recurrence of placenta praevia: a population-based study.
AB  - We determined recent trends and recurrence rates of placenta praevia in 790,366
      deliveries in NSW. From 2001 to 2009, the rate of placenta praevia increased by
      26%, from 0. 69% to 0. 87% (trend P < 0.001). The placenta praevia recurrence
      rate in a second birth was 4.8%. Two-thirds of the increase in placenta praevia
      was accounted for by trends in known risk factors, and the unexplained portion
      may reflect changes in unidentified risk factors or in the threshold for placenta
      praevia diagnosis.

PMID- 22862286
TI  - The large sample size fallacy.
AB  - BACKGROUND: Significance in the statistical sense has little to do with
      significance in the common practical sense. Statistical significance is a
      necessary but not a sufficient condition for practical significance. Hence,
      results that are extremely statistically significant may be highly nonsignificant
      in practice. The degree of practical significance is generally determined by the
      size of the observed effect, not the p-value. The results of studies based on
      large samples are often characterized by extreme statistical significance despite
      small or even trivial effect sizes. Interpreting such results as significant in
      practice without further analysis is referred to as the large sample size fallacy
      in this article. AIM: The aim of this article is to explore the relevance of the
      large sample size fallacy in contemporary nursing research. RESULTS: Relatively
      few nursing articles display explicit measures of observed effect sizes or
      include a qualitative discussion of observed effect sizes. Statistical
      significance is often treated as an end in itself. CONCLUSION: Effect sizes
      should generally be calculated and presented along with p-values for
      statistically significant results, and observed effect sizes should be discussed
      qualitatively through direct and explicit comparisons with the effects in related
      literature.

PMID- 22862287
TI  - A need for an exchange on medical education between FM/GP stakeholders in Europe.

PMID- 22862288
TI  - Long-term perturbation of spine plasticity results in distinct impairments of
      cognitive function.
AB  - Dendritic spines serve as the post-synaptic structural component of synapses. The
      structure and function of dendritic spines are dynamically regulated by a number
      of signaling pathways and allow for normal neural processing, whereas aberrant
      spine changes are thought to contribute to cognitive impairment in
      neuropsychiatric and neurodegenerative disorders. However, spine changes within
      different brain regions and their contribution to specific cognitive functions,
      especially later in adulthood, is not well understood. In this study, we used
      late-adult KALRN-deficient mice as a tool to investigate the vulnerability of
      different cognitive functions to long-term perturbations in spine plasticity in
      different forebrain regions. We found that in these mice, loss of one or both
      copies of KALRN lead to genotype and brain region-dependent reductions in spine
      density. Surprisingly, heterozygote and knockout mice showed differential
      impairments in cognitive phenotypes, including working memory, social
      recognition, and social approach. Correlation analysis between the site and
      magnitude of spine loss and behavioral alterations suggests that the interplay
      between brain regions is critical for complex cognitive processing and
      underscores the importance of spine plasticity in normal cognitive function. Long
      term perturbation of spine plasticity results in distinct impairments of
      cognitive function. Using genetically modified mice deficient in a central
      regulator of spine plasticity, we investigated the brain region-specific
      contribution of spine numbers to various cognitive functions. We found distinct
      cognitive functions display differential sensitivity to spine loss in the cortex
      and hippocampus. Our data support spines as neuronal structures important for
      cognition and suggest interplay between brain regions is critical for complex
      cognitive processing.

PMID- 22862289
TI  - Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal
      squamous cell carcinoma patients: results of a pilot study.
AB  - Concurrent chemoradiotherapy is the standard treatment for patients with locally
      advanced esophageal squamous cell carcinoma. However, a number of patients
      present intolerance to chemoradiotherapy because of advanced age or malnutrition.
      Erlotinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, was
      shown to be effective in treating esophageal carcinoma, with mild toxicities. In
      this pilot study, we investigated the safety and efficacy of concurrent erlotinib
      and radiotherapy as an alternative treatment modality for esophageal carcinoma
      patients who are intolerant to chemoradiotherapy. Pathologically diagnosed
      esophageal squamous cell carcinoma patients who could not tolerate concurrent
      chemoradiotherapy were enrolled. All patients were treated with concurrent
      erlotinib and intensity-modulated radiation therapy. Erlotinib was given orally
      for 60 days (150 mg per day). Radiotherapy (total dose, 60 Gy) was given at
      dosages of 2 Gy for a total of 30 times. Immunohistochemical staining was
      performed to assess epidermal growth factor receptor expression. Toxicities were
      evaluated according to the National Cancer Institute Common Terminology Criteria
      for Adverse Events (version 3.0). The overall survival, progression-free
      survival, and local-regional relapse-free survival were calculated using the
      Kaplan-Meier method. Between December 2007 and March 2011, 18 patients were
      enrolled. The median age was 71.5 years. Primary disease was stages II, III, and
      IV in 3, 8, and 4 patients, respectively. There were three patients with
      recurrent disease after radical surgery. The median follow-up time was 17.2
      months. Grade 3 esophagitis and skin rash were observed in five (27.8%) and two
      (11.1%) patients, respectively. Radiation pneumonitis of grades 2 and 5 was
      observed in one patient each. No grade 3/4 impaired liver function or
      hematological toxicity was observed. At 1 month after radiotherapy, two (11.1%)
      patients achieved complete response, 11 (61.1%) patients achieved partial
      response, and 5 (27.8%) patients had stable disease. The median time of overall
      survival and progression-free survival was 21.1 and 12 months, respectively. Two
      year overall survival, progression-free survival, and local-regional relapse-free
      survival were 44.4%, 38.9%, and 66.7%, respectively. Five of six patients
      examined for epidermal growth factor receptor had high expression levels (3+).
      The relationship between epidermal growth factor receptor expression and
      treatment outcomes could not be concluded. For esophageal squamous cell carcinoma
      patients who cannot tolerate chemoradiotherapy, concurrent erlotinib and
      radiotherapy are tolerable and effective. Valuable markers to predict the effect
      of erlotinib should be exploited in future studies. 

PMID- 22862290
TI  - Novel pyrazole compounds for pharmacological discrimination between receptor
      operated and store-operated Ca(2+)  entry pathways.
AB  - BACKGROUND AND PURPOSE: Pyrazole derivatives have recently been suggested as
      selective blockers of transient receptor potential cation (TRPC) channels but
      their ability to distinguish between the TRPC and Orai pore complexes is ill
      defined. This study was designed to characterize a series of pyrazole derivatives
      in terms of TRPC/Orai selectivity and to delineate consequences of selective
      suppression of these pathways for mast cell activation. EXPERIMENTAL APPROACH:
      Pyrazoles were generated by microwave-assisted synthesis and tested for effects
      on Ca(2+)  entry by Fura-2 imaging and membrane currents by patch-clamp
      recording. Experiments were performed in HEK293 cells overexpressing TRPC3 and in
      RBL-2H3 mast cells, which express classical store-operated Ca(2+)  entry mediated
      by Orai channels. The consequences of inhibitory effects on Ca(2+)  signalling in
      RBL-2H3 cells were investigated at the level of both degranulation and nuclear
      factor of activated T-cells activation. KEY RESULTS: Pyr3, a previously suggested
      selective inhibitor of TRPC3, inhibited Orai1- and TRPC3-mediated Ca(2+)  entry
      and currents as well as mast cell activation with similar potency. By contrast,
      Pyr6 exhibited a 37-fold higher potency to inhibit Orai1-mediated Ca(2+)  entry
      as compared with TRPC3-mediated Ca(2+)  entry and potently suppressed mast cell
      activation. The novel pyrazole Pyr10 displayed substantial selectivity for TRPC3
      mediated responses (18-fold) and the selective block of TRPC3 channels by Pyr10
      barely affected mast cell activation. CONCLUSIONS AND IMPLICATIONS: The pyrazole
      derivatives Pyr6 and Pyr10 are able to distinguish between TRPC and Orai-mediated
      Ca(2+)  entry and may serve as useful tools for the analysis of cellular
      functions of the underlying Ca(2+)  channels.

PMID- 22862291
TI  - Gene silencing by gold nanoshell-mediated delivery and laser-triggered release of
      antisense oligonucleotide and siRNA.
AB  - RNA interference (RNAi)--using antisense DNA or RNA oligonucleotides to silence
      activity of a specific pathogenic gene transcript and reduce expression of the
      encoded protein--is very useful in dissecting genetic function and holds
      significant promise as a molecular therapeutic. A major obstacle in achieving
      gene silencing with RNAi technology is the systemic delivery of therapeutic
      oligonucleotides. Here we demonstrate an engineered gold nanoshell (NS)-based
      therapeutic oligonucleotide delivery vehicle, designed to release its cargo on
      demand upon illumination with a near-infrared (NIR) laser. A poly-L-lysine
      peptide (PLL) epilayer covalently attached to the NS surface (NS-PLL) is used to
      capture intact, single-stranded antisense DNA oligonucleotides, or alternatively,
      double-stranded short-interfering RNA (siRNA) molecules. Controlled release of
      the captured therapeutic oligonucleotides in each case is accomplished by
      continuous wave NIR laser irradiation at 800 nm, near the resonance wavelength of
      the nanoshell. Fluorescently tagged oligonucleotides were used to monitor the
      time-dependent release process and light-triggered endosomal release. A green
      fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used
      to determine cellular uptake and gene silencing mediated by the NS-PLL carrying
      GFP gene-specific single-stranded DNA antisense oligonucleotide (AON-GFP), or a
      double-stranded siRNA (siRNA-GFP), in vitro. Light-triggered delivery resulted in
      ~47% and ~49% downregulation of the targeted GFP expression by AON-GFP and siRNA
      GFP, respectively. Cytotoxicity induced by both the NS-PLL delivery vector and by
      laser irradiation is minimal, as demonstrated by a XTT cell proliferation assay.

PMID- 22862292
TI  - Altitudinal variation in egg retention and rates of embryonic development in
      oviparous Zootoca vivipara fits predictions from the cold-climate model on the
      evolution of viviparity.
AB  - The evolution of reptilian viviparity is favoured, according to the cold-climate
      hypothesis, at high latitudes or altitudes, where egg retention would entail
      thermal benefits for embryogenesis because of maternal thermoregulation.
      According to this hypothesis, and considering that viviparity would have evolved
      through a gradual increase in the extent of intrauterine egg retention, highland
      oviparous populations are expected to exhibit more advanced embryo development at
      oviposition than lowland populations. We tested for possible differences in the
      level of egg retention, embryo development time and thermal biology of oviparous
      Zootoca vivipara near the extreme altitudinal limits of the species distribution
      in the north of Spain (mean altitude for lowland populations, 235 m asl.; for
      highland populations, 1895 m asl.). Altitude influenced neither temperature of
      active lizards in the field nor temperature selected by lizards in a laboratory
      thermal gradient, and pregnant females selected lower temperatures in the thermal
      gradient than did males and nonpregnant females across altitudinal levels. Eggs
      from highland populations contained embryos more developed at the time of
      oviposition (Dufaure and Hubert's stages 33-35) than eggs of highland populations
      (stages 30-34) and partly because of this difference incubation time was shorter
      for highland embryos. When analysed for clutches from both altitudinal extremes
      at the same embryonic stage at oviposition (stage 33), again incubation time was
      shorter for highland populations, indicating genuine countergradient variation in
      developmental rate. Our results indicate that temperature is an environmental
      factor affecting the geographical distribution of different levels of egg
      retention in Z. vivipara, as predicted by the cold-climate hypothesis on the
      evolution of viviparity.

PMID- 22862293
TI  - An environmental epigenetic study of  ADRB2 5'-UTR methylation and childhood
      asthma severity.
AB  - BACKGROUND: Beta-2 adrenergic receptor (ADRB2) is the primary target of both
      short- and long-acting beta-agonist asthma medications. ADRB2 5'-UTR methylation
      changes in blood have the potential to act as a surrogate biomarker of
      responsiveness to beta-agonist treatment and childhood asthma severity.
      OBJECTIVE: To study the association between ADRB2 5'-UTR methylation, NO (2) 
      exposure and childhood asthma severity. METHODS: We compared ADRB2 5'-UTR
      methylation levels in blood between 60 children with mild asthma and 122 children
      with severe asthma using methylation-specific PCR. We also investigated potential
      joint effects between NO (2)  exposure and ADRB2 5'-UTR methylation. RESULTS: We
      found a significant association between intermediate (OR: 4.11, 95% CI: 1.58
      10.73) and high levels (OR: 7.63, 95% CI: 3.02-19.26) of ADRB2 methylation and
      severe childhood asthma. In addition, we found a significant association between
      indoor exposure to NO (2) , an air pollutant and known asthmogen, and severe
      asthma among children exhibiting high ADRB2 methylation (OR: 4.59, 95% CI: 1.03
      20.55) but no association among children exhibiting low levels of ADRB2
      methylation (OR: 0.35, 95% CI: 0.01-14.13). CONCLUSIONS AND CLINICAL RELEVANCE:
      These findings support the potential use of ADRB2 5'-UTR methylation as a
      biomarker of both asthma severity and risk for NO (2) -associated asthma
      exacerbations in children, and present the first evidence of an epigenetic link
      between an important environmental exposure and childhood asthma severity.

PMID- 22862294
TI  - The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4
      pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual
      endothelin receptor antagonist.
AB  - Starting from the structure of bosentan (1), we embarked on a medicinal chemistry
      program aiming at the identification of novel potent dual endothelin receptor
      antagonists with high oral efficacy. This led to the discovery of a novel series
      of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan,
      ACT-064992) emerged as particularly interesting as it is a potent inhibitor of
      ET(A) with significant affinity for the ET(B) receptor and shows excellent
      pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt
      sensitive rats. Compound 17 successfully completed a long-term phase III clinical
      trial for pulmonary arterial hypertension.

PMID- 22862295
TI  - Phthalates in indoor dust in Kuwait: implications for non-dietary human exposure.
AB  - Phthalates are semivolatile organic compounds with a ubiquitous environmental
      distribution. Their presence in indoor environments is linked to their use in a
      variety of consumer products such as children's toys, cosmetics, food packaging,
      flexible PVC flooring among others. The goal of this study was to investigate the
      occurrence and concentration of phthalates in dust from homes in Kuwait and to
      assess non-dietary human exposure to these phthalates. Dust samples were randomly
      collected from 21 homes and analyzed for eight phthalates. The concentrations of
      total phthalates were log normally distributed and ranged from 470 to 7800 MUg/g.
      Five phthalates [Di(2-ethylhexyl) phthalate (DEHP), Di-n-octyl phthalate (DnOP),
      Di-n-butyl phthalate (DBP), Benzyl butyl phthalate (BzBP), and Dicyclohexyl
      phthalate (DcHP)] were routinely detected. The major phthalate compound was DEHP
      at a geometric mean concentration of 1704 MUg/g (median, 2256 MUg/g) accounting
      for 92% of the total phthalates measured. Using the measured concentrations and
      estimates of dust ingestion rates for children and adults, estimated human non
      dietary exposure based on median phthalate concentrations ranged from 938 ng/kg
      bd/day for adults to 13362 ng/kg-bd/day for toddlers. The difference in exposure
      estimates between children and adults in this study supports previous reports
      that children are at greater risk from pollutants that accumulate indoors.

PMID- 22862296
TI  - Involvement of AMPA receptors in CSD-induced impairment of LTP in the
      hippocampus.
AB  - OBJECTIVE: To investigate the alteration of hippocampal long-term plasticity and
      basal synaptic transmission induced by repetitive cortical spreading depressions
      (CSDs). BACKGROUND: There is a relationship between migraine aura and amnesia
      attack. CSD, a state underlying migraine attacks, may be responsible for
      hippocampus-related symptoms. However, the precise role of CSD on hippocampal
      activity has not been investigated. METHODS: Male Wistar rats were divided into
      CSD and control groups. Repetitive CSDs were induced in vivo by topical
      application of solid KCl. Forty-five minutes later, the ipsilateral hippocampus
      was removed, and hippocampal slices were prepared for a series of
      electrophysiological studies. RESULTS: Repetitive CSDs led to a decrease in the
      magnitude of long-term potentiation in the hippocampus. CSD also reduced
      hippocampal synaptic efficacy, as shown by a reduction in post-synaptic alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses. In
      contrast, the post-synaptic N-methyl-d-aspartate receptor responses remained
      unchanged. In addition, there were no changes in paired-pulse profiles between
      the groups, indicating that CSD did not induce any presynaptic alterations.
      CONCLUSION: These findings suggest that a reduction of post-synaptic alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses is the mechanism
      responsible for impaired hippocampal long-term potentiation induced by CSD.

PMID- 22862297
TI  - Relationship between cutoff values of peak aortic valve velocity and those of
      other Doppler echocardiographic parameters of severity in patients with aortic
      stenosis and normal flow.
AB  - BACKGROUND: Previous studies have reported inconsistencies between
      echocardiographic parameters of severity in aortic valve stenosis (AS). Peak
      aortic valve velocity (Vmax ) strongly predicts outcome in AS patients. This
      study was therefore designed to identify the cutoff values of echocardiographic
      parameters of severity corresponding to a Vmax >= 3 m/sec, >=4 m/sec, 5 m/sec, or
      5.50 m/sec in a large cohort of patients with normal flow (NF) AS. METHODS AND
      RESULTS: We retrospectively reviewed the echocardiograms of 528 consecutive
      patients with normal flow (NF) AS, left ventricular (LV) ejection fraction
      >=0.50, and NF (stroke volume index > 35 mL/m2). The values of mean pressure
      gradient (MPG), aortic valve area (AVA), and indexed aortic valve area (IAVA)
      corresponding to Vmax >= 3 m/sec obtained from receiver operating characteristic
      (ROC) curves analysis were 22 mmHg, 1.15 cm(2) , and 0.60 cm(2) /m(2) ,
      respectively. While a cutoff of Vmax >= 4 m/sec to define severe AS was
      consistent with a value of 39 mmHg for MPG, corresponding values for AVA and IAVA
      of 0.90 cm2 and 0.48 cm2/m2, respectively, were substantially different from
      those recommended in current guidelines. MPG >=60 and 65 mmHg, AVA <=0.76 and
      <=0.68 cm2, and IAVA <=0.41 and <=0.35 cm(2) /m(2) were related to a Vmax >=5 and
      >=5.5 m/sec (very severe AS), respectively. CONCLUSIONS: Guidelines recommended
      cutoff values for AVA and IAVA are not consistent with those of Vmax and MPG. The
      results of this study may serve as safeguard in case of apparent inconsistencies
      between echocardiographic parameters of severity in NF AS.

PMID- 22862298
TI  - Sexual adjustment counseling for women with chronic pelvic pain.
AB  - Sexual concerns are common in women with chronic pelvic pain and often remain
      unresolved when pain improves. Therefore, to restore pelvic function, treatment
      should address sexuality in addition to pain. In this article, I describe sexual
      challenges experienced by women with chronic pelvic pain, introduce a modified
      sexuality counseling model, and suggest sexuality resources and training for
      gynecologic nurses and other health care providers who are ideally positioned to
      offer sexuality counseling to this population. 

PMID- 22862299
TI  - Prospective cohort study about the lymphocyte subpopulations' change and impact
      on the pregnancy outcome in fetal growth restriction.
AB  - OBJECTIVE: To evaluate lymphocyte subpopulations' change and impact on the
      pregnancy outcome in fetal growth restriction (FGR) through a prospective cohort
      study. METHODS: Sixty singleton pregnancies with FGR and 20 normal pregnant women
      were enrolled at the third trimester of pregnancy in this study. FGR was defined
      according to fundal height and abdominal circumference through obstetric
      examination and ultrasound examination. Third trimester peripheral blood and
      umbilical cord blood lymphocyte subpopulations were analysed by flow cytometry.
      The cytotoxic activity of lymphocytes using umbilical cord blood mononuclear
      activated kill cells as the effector cells, K562 cells as the target cells was
      measured by MTT deoxidation assay. RESULTS: There were no significant differences
      about the age, parity, gestational age enrolled, BMI before pregnancy between the
      FGR and control group. The birth weight, length and head circumference of the
      neonates from FGR group were less than that from normal control. The percentages
      of B-lymphocytes in peripheral blood at the third trimester were significantly
      increased in FGR group compared to that in control group (P < 0.05). In umbilical
      cord blood, FGR group had a higher percentage of both CD3 and CD4 lymphocyte,
      lower absolute cell counts and percentage of B-lymphocyte, and higher CD4/CD8
      ratio than control group (P < 0.05). Most importantly, the kill cell activity of
      the lymphocytes in cord blood from FGR group was significantly higher than that
      from control group (P < 0.05). The significant positive correlations were also
      found that the percentage and number of B lymphocytes in umbilical cord blood
      with birthweight, birthlength and birth head circumference, but CD4/CD8 ratio,
      the kill cell activity in umbilical cord blood had negative correlations with
      that. The percentage of B lmyphocyte in third trimester and CD4/CD8 ratio, kill
      cell activity in umbilical cord blood are associated with an increased risk of
      prematurity and SGA birth, but contrary result was found with the percentage and
      number of B lmyphocyte in cord blood. CONCLUSIONS: Fetal immunological rejection
      could be involved in the pathogenesis of FGR. The changes of T lymphocyte
      subpopulations and B-cells, enhanced kill cell activity might cause FGR and
      preterm birth.

PMID- 22862300
TI  - Reflecting on the accomplishments of Health Communication.

PMID- 22862301
TI  - Comparison of autologous bone marrow mononuclear cells transplantation and
      mobilization by granulocyte colony-stimulating factor in experimental spinal
      injury.
AB  - BACKGROUND: Recent studies have shown that autologous adult stem cells may be a
      protocol of treatment for spinal cord injury (SCI) in humans. The purpose of this
      study was to compare the effect of an injection of autologous bone marrow
      mononuclear cells (BMMCs) and bone-marrow cell mobilization induced by
      granulocyte colony stimulating factor (G-CSF) in rats with SCI. METHODS: Adult
      rats were assigned into three groups: control group (SCI only), SCI + BMMCs, and
      SCI + G - CSF. Neurological scores and electrophysiological testing were done in
      all rats before SCI, and at 1, 7, 14, 28, 56 days post-SCI. Simultaneously,
      immunohistochemical labeling and TUNEL assay were performed at the given time.
      RESULTS: From 1 week post-SCI onward, animals treated with BMMCs or G-CSF had
      higher BBB scores than control group. Motor and somatosensory evoked potentials
      (MEPs and SEPs, respectively) of the treated group were significantly better than
      those in control group at 2 weeks. After sacrifice, compared with the control,
      animals treated with BMMCs and G-CSF significantly increased expressions of Brdu,
      NSE, GFAP, Factor VIII, BDNF, and reduced expression of apoptosis cells around
      the lesion site. Our results indicate that administration of BMMCs and G-CSF in a
      SCI model achieves similarly positive effect on functional and histologic
      recovery. CONCLUSIONS: The use of G-CSF may be a viable alternative to BMMCs for
      autograft in patients with SCI.

PMID- 22862302
TI  - Context-dependent impairment of recollection in list-method directed forgetting.
AB  - In list-method directed forgetting, people's ability to forget one of the sets of
      learned material is examined. Research shows that memory for to-be-forgotten
      items is impaired when assessed by a recall test and by recognition tests reliant
      on recollective processes. Retrieval inhibition and context-change mechanisms
      have been proposed to account for the directed forgetting effects and both of
      them account for the results obtained with recognition tests. However, the
      context change account makes a specific prediction that recollection is impaired
      by directed forgetting only if it makes use of contextual associations. In the
      present study, directed forgetting was examined with two types of recollection
      based tasks making use of different types of associations, namely a list
      discrimination task utilising contextual associations and an associative
      recognition task utilising interitem associations. Consistent with the context
      change account, the costs of directed forgetting were observed in a list
      discrimination task and were not observed in an associative recognition task. The
      results indicate that impairment in recollection due to directed forgetting is
      not general and provide converging evidence to support the context-change
      account.

PMID- 22862303
TI  - beta-Sheet core of tau paired helical filaments revealed by solid-state NMR.
AB  - One of the hallmarks of Alzheimer's disease is the self-assembly of the
      microtubule-associated protein tau into fibers termed "paired helical filaments"
      (PHFs). However, the structural basis of PHF assembly at atomic detail is largely
      unknown. Here, we applied solid-state nuclear magnetic resonance (ssNMR)
      spectroscopy to investigate in vitro assembled PHFs from a truncated three-repeat
      tau isoform (K19) that represents the core of PHFs. We found that the rigid core
      of the fibrils is formed by amino acids V306 to S324, only 18 out of 99 residues,
      and comprises three beta-strands connected by two short kinks. The first beta
      strand is formed by the well-studied hexapeptide motif VQIVYK that is known to
      self-aggregate in a steric zipper arrangement. Results on mixed [(15)N:(13)C]
      labeled K19 fibrils show that beta-strands are stacked in a parallel, in-register
      manner. Disulfide bridges formed between C322 residues of different molecules
      lead to a disturbance of the beta-sheet structure, and polymorphism in ssNMR
      spectra is observed. In particular, residues K321-S324 exhibit two sets of
      resonances. Experiments on K19 C322A PHFs further confirm the influence of
      disulfide bond formation on the core structure. Our structural data are supported
      by H/D exchange NMR measurements on K19 as well as a truncated four-repeat
      isoform of tau (K18). Site-directed mutagenesis studies show that single-point
      mutations within the three different beta-strands result in a significant loss of
      PHF aggregation efficiency, highlighting the importance of the beta-structure
      rich regions for tau aggregation.

PMID- 22862304
TI  - Adsorption of insecticidal Cry1Ab protein to humic substances. 1. Experimental
      approach and mechanistic aspects.
AB  - Adsorption is a key process affecting the fate of insecticidal Cry proteins (Bt
      toxins), produced by genetically modified Bt crops, in soils. However, the
      mechanisms of adsorption to soil organic matter (SOM) remain poorly understood.
      This work assesses the forces driving the adsorption of Cry1Ab to Leonardite
      humic acid (LHA), used as a model for SOM. We studied the effects of solution pH
      and ionic strength (I) on adsorption using a quartz crystal microbalance with
      dissipation monitoring and optical waveguide lightmode spectroscopy. Initial
      Cry1Ab adsorption rates were close to diffusion-limited and resulted in extensive
      adsorption, even at pH >6, at which LHA and Cry1Ab carry negative net charges.
      Adsorption increased with decreasing I at pH >6, indicating Cry1Ab-LHA patch
      controlled electrostatic attraction via positively charged domains of Cry1Ab.
      Upon rinsing, only a fraction of Cry1Ab desorbed, suggesting a range of
      interaction energies of Cry1Ab with LHA. Different interaction energies likely
      resulted from nonuniformity in the LHA surface polarity, with higher Cry1Ab
      affinities to more apolar LHA regions due to the hydrophobic effect.
      Contributions from the hydrophobic effect were substantiated by comparison of the
      adsorption of Cry1Ab and the reference proteins albumin and lysozyme to LHA and
      to apolar and polar model surfaces.

PMID- 22862307
TI  - Drug-induced gynecomastia: an evidence-based review.
AB  - INTRODUCTION: Drugs are estimated to cause about 10 - 25% of all cases of
      gynecomastia. Over the course of several decades, multiple medications have been
      implicated in the development of gynecomastia mostly in the form of case reports
      and case series. However, these reports suffer from a multitude of deficiencies,
      including poor quality of evidence. AREAS COVERED: Studies were selected for this
      review by performing an extensive electronic and hand-search using BIOSIS, EMBASE
      and Medline, from 1940 to present, for all reported drug associations of
      gynecomastia and their possible pathophysiology. Quality of evidence was assessed
      on a three-point scale: good, fair and poor, and each of the drugs reported to
      cause gynecomastia was assigned a level of strength. The pathophysiology of
      gynecomastia is also discussed in detail for each of the drugs found to have a
      good or fair evidence of association with gynecomastia. EXPERT OPINION: Most of
      the reported drug-gynecomastia associations were based on poor quality evidence.
      The drugs definitely associated with the onset of gynecomastia are
      spironolactone, cimetidine, ketoconazole, hGH, estrogens, hCG, anti-androgens,
      GnRH analogs and 5-alpha reductase inhibitors. Medications probably associated
      with gynecomastia include risperidone, verapamil, nifedipine, omeprazole,
      alkylating agents, HIV medications (efavirenz), anabolic steroids, alcohol and
      opioids.

PMID- 22862305
TI  - Effects of kinin B(1)  and B(2)  receptor antagonists on overactive urinary
      bladder syndrome induced by spinal cord injury in rats.
AB  - BACKGROUND AND PURPOSE: Kinin B(1)  and B(2)  receptors have been implicated in
      physiological and pathological conditions of the urinary bladder. However, their
      role in overactive urinary bladder (OAB) syndrome following spinal cord injury
      (SCI) remains elusive. EXPERIMENTAL APPROACH: We investigated the role of kinin
      B(1)  and B(2)  receptors in OAB after SCI in rats. KEY RESULTS: SCI was
      associated with a marked inflammatory response and functional changes in the
      urinary bladder. SCI resulted in an up-regulation of B(1)  receptor mRNA in the
      urinary bladder, dorsal root ganglion and spinal cord, as well as in B(1) 
      protein in the urinary bladder and B(1)  and B(2)  receptor protein in spinal
      cord. Interestingly, both B(1)  and B(2)  protein expression were similarly
      distributed in detrusor muscle and urothelium of animals with SCI. In vitro
      stimulation of urinary bladder with the selective B(1)  or B(2)  agonist elicited
      a higher concentration-response curve in the SCI urinary bladder than in naive or
      sham urinary bladders. Cystometry revealed that treatment of SCI animals with the
      B(2)  selective antagonist icatibant reduced the amplitude and number of non
      voiding contractions (NVCs). The B(1)  antagonist des-Arg(9) -[Leu(8) ]
      bradykinin reduced the number of NVCs while the non-peptide B(1)  antagonist
      SSR240612 reduced the number of NVCs, the urinary bladder capacity and increased
      the voiding efficiency and voided volume. CONCLUSIONS AND IMPLICATIONS: Taken
      together, these data show the important roles of B(1)  and B(2)  receptors in OAB
      following SCI in rats and suggest that blockade of these receptors could be a
      potential therapeutic target for controlling OAB.

PMID- 22862417
TI  - First description of ColE-type plasmid in Aeromonas spp. carrying quinolone
      resistance (qnrS2) gene.
AB  - AIMS: Isolation and full sequence analysis of ColE-type plasmid, which carries
      the qnrS2 gene. METHODS AND RESULTS: Quinolone resistance (qnrS2) gene-carrying
      plasmids were isolated from Aeromonas sobria and Aeromonas hydrophila strains,
      and plasmid sequencing was achieved by a primer-walking approach. The total sizes
      of these plasmids (pAQ2-1 and pAQ2-2) were 6900 bp and 6903 bp, respectively, and
      they were 99.1% identical to each other. The genes (oriV and repA) for plasmid
      replication were organized similar to the corresponding genes in the ColE2-type
      plasmids, pAsa3 and pAsa1, isolated from Aeromonas salmonicida subsp.
      salmonicida, but the gene (mobA) for mobilization was homologue to ColE1-type
      plasmid (pAsa2) from Aer. salmonicida subsp. salmonicida. Additionally, the qnrS2
      gene was part of a mobile insertion cassette element in the plasmid. CONCLUSIONS:
      Two plasmids were assumed to be the same plasmid, and this identification of a
      plasmid-mediated qnrS2 gene from the two different strains underlines a possible
      diffusion of these resistance determinants in an aquaculture system. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This is the first finding of the ColE-type plasmid
      carrying the qnrS2 gene.

PMID- 22862418
TI  - Parental interaction with infants treated with medical technology.
AB  - BACKGROUND: It is well established that parents must interact with their new-born
      babies to facilitate attachment. However, very little is known about how parents
      perceive different types of medical technology products commonly used in the
      neonatal intensive care unit (NICU) as barriers to their wish to interact with
      their infants. AIM: This study aims to examine to what extent the different
      medical technology products commonly used in the NICU are perceived by parents to
      be obstacles in their wish to interact with their babies. DESIGN AND METHODS: In
      2010, a cross-sectional survey, using a questionnaire specifically developed for
      this study, was conducted among the parents of children who were discharged from
      any of the five NICUs of the Vastra Gotaland region in Sweden. A consecutive
      sample of 248 parents participated, and multiple regressions and t-tests were
      used to analyse the data. RESULTS: The parents generally perceived the various
      medical technology products differently, according to the perceived level of
      obstruction. The variables of gender, age, educational level, origin, gestational
      age, previous experience of being a parent, and the offer of accommodation at the
      NICU were significantly associated with the perceived level of obstruction in the
      parents' wish to interact with their baby while the baby was being treated with
      different medical technology products. CONCLUSION: The primary implication for
      practice is that to facilitate attachment, nurses should involve different
      categories of parents in different ways in the care of their children, depending
      on the equipment being used in the treatment of the children. Thus, the
      individual care plan should explicitly include the details of the specific
      medical equipment, because although its use is medically beneficial for the
      child, it is associated with potential liabilities regarding parent-child
      interaction and, consequently, regarding parent-child attachment.

PMID- 22862419
TI  - Pubertal stage and measures of adiposity in British schoolchildren.
AB  - BACKGROUND: Puberty is a critical period in the development of obesity. Body mass
      index (BMI), waist circumference and skin-fold thickness are used generally as
      estimates of body fat in children and adults. AIM: To identify a marker of
      adiposity that is independent of pubertal status and determine its relationship
      to physical fitness in adolescence. SUBJECTS AND METHODS: Girls (n = 147) and
      boys (n = 100) from year 8 in three Welsh schools self-reported Tanner stages.
      Anthropometric measurements of adiposity were made and aerobic fitness estimated
      with a 20-metre shuttle-run test. RESULTS: Children in early and late puberty
      were of similar chronological age. BMI strongly correlated with height in early
      puberty in girls (r = 0.366, p < 0.001) and boys (r = 0.594, p < 0.001), but not
      in late puberty. Waist-to-height ratio adjusted for the effect of height on waist
      measurements; and correlated with percentage fat mass in early and late puberty
      in girls (r = 0.865 and r = 0.772, both p < 0.001) and boys (r = 0.868 and r =
      0.877, both p < 0.001). Physical fitness score was inversely related to waist-to
      height ratio, with similar regression lines in early and late puberty, in girls
      (r = - 0.545, p < 0.001 and r = - 0.362, p = 0.005) and boys (r = - 0.490, p <
      0.001 and r = - 0.400, p = 0.003). CONCLUSION: Pubertal status should be taken
      into account in adjusting weight for height in adolescents. Waist-to-height ratio
      is a convenient and appropriate measure of adiposity during puberty.

PMID- 22862420
TI  - Matrix metalloproteinase-3 in the central nervous system: a look on the bright
      side.
AB  - Matrix metalloproteinases (MMPs) are a large family of proteases involved in many
      cell-matrix and cell-cell signalling processes through activation, inactivation
      or release of extracellular matrix (ECM) and non-ECM molecules, such as growth
      factors and receptors. Uncontrolled MMP activities underlie the pathophysiology
      of many disorders. Also matrix metalloproteinase-3 (MMP-3) or stromelysin-1
      contributes to several pathologies, such as cancer, asthma and rheumatoid
      arthritis, and has also been associated with neurodegenerative diseases like
      Alzheimer's disease, Parkinson's disease and multiple sclerosis. However, based
      on defined MMP spatiotemporal expression patterns, the identification of novel
      candidate molecular targets and in vitro and in vivo studies, a beneficial role
      for MMPs in CNS physiology and recovery is emerging. The main purpose of this
      review is to shed light on the recently identified roles of MMP-3 in normal brain
      development and in plasticity and regeneration after CNS injury and disease. As
      such, MMP-3 is correlated with neuronal migration and neurite outgrowth and
      guidance in the developing CNS and contributes to synaptic plasticity and
      learning in the adult CNS. Moreover, a strict spatiotemporal MMP-3 up-regulation
      in the injured or diseased CNS might support remyelination and neuroprotection,
      as well as genesis and migration of stem cells in the damaged brain.

PMID- 22862421
TI  - Mesenchymal stem cells as a novel carrier for targeted delivery of gene in cancer
      therapy based on nonviral transfection.
AB  - The success of gene therapy relies largely on an effective targeted gene delivery
      system. Till recently, more and more targeted delivery carriers, such as
      liposome, nanoparticles, microbubbles, etc., have been developed. However, the
      clinical applications of these systems were limited for their several
      disadvantages. Therefore, design and development of novel drug/gene delivery
      vehicles became a hot topic. Cell-based delivery systems are emerging as an
      alternative for the targeted delivery system as we described previously.
      Mesenchymal stem cells (MSCs) are an attractive cell therapy carrier for the
      delivery of therapeutic agents into tumor sites mainly for their tumor-targeting
      capacities. In the present study, a nonviral vector, PEI(600)-Cyd, prepared by
      linking low molecular weight polyethylenimine (PEI) and beta-cyclodextrin (beta
      CD), was used to introduce the therapeutical gene, tumor necrosis factor (TNF)
      related apoptosis-inducing ligand (TRAIL), to MSCs. Meanwhile, the
      characterization, transfection efficiency, cytotoxicity, cellular
      internalization, and its mechanism of this nonviral vector were evaluated. The in
      vitro expression of TRAIL from MSCs-TRAIL was demonstrated by both enzyme-linked
      immunosorbent assay and Western blot analysis. The lung tumor homing ability of
      MSCs was further confirmed by the in vitro and in vivo model. Moreover, the
      therapeutic effects as well as the safety of MSCs-TRAIL on lung metastases
      bearing C57BL/6 mice and normal C57BL/6 mice were also demonstrated. Our results
      supported both the effectiveness of nonviral vectors in transferring the
      therapeutic gene to MSCs and the feasibility of using MSCs as a targeted gene
      delivery carrier, indicating that MSCs could be a promising tumor target delivery
      vehicle in cancer gene therapy based on nonviral gene recombination.

PMID- 22862422
TI  - Multimodality evaluation of patients with gastroesophageal reflux disease
      symptoms who have failed empiric proton pump inhibitor therapy.
AB  - Patients with symptoms suggestive of gastroesophageal reflux disease (GERD), such
      as chest pain, heartburn, regurgitation, and dysphagia, are typically treated
      initially with a course of proton pump inhibitors (PPIs). The evaluation of
      patients who have either not responded at all or partially and inadequately
      responded to such therapy requires a more detailed history and may involve an
      endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory
      esophageal pH monitoring, and gastric emptying scanning. To assess the merits of
      a multimodality 'structural' and 'functional' assessment of the esophagus in
      patients who have inadequately controlled GERD symptoms despite using empiric
      PPI, a retrospective cohort study of patients without any response or with poor
      symptomatic control to empiric PPI (>2 months duration) who were referred to an
      Esophageal Studies Unit was conducted. Patients were studied using symptom
      questionnaires, endoscopy (+ or - for erosive disease, or Barrett's metaplasia)
      and multilevel esophageal biopsies (eosinophilia, metaplasia), esophageal
      motility (aperistalsis, dysmotility), 24-hour ambulatory esophageal pH monitoring
      (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10%
      retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men
      and 128 women) aged 16-89 years underwent complete multimodality testing. Forty
      percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]
      , biopsy-, pH+); 19.3% (n= 53) had erosive esophagitis (EGD+); 5.5% (n= 15)
      Barrett's esophagus (EGD+, metaplasia+); 5.5% (n= 15) eosinophilic esophagitis
      (biopsy+); 2.5% (n= 7) had achalasia and 5.8% (n= 16) other dysmotility
      (motility+, pH-); 16% (n= 44) had functional heartburn (EGD-, pH-), and 5.8% (n=
      16) had gastroparesis (gastric scan+). Cumulative symptom scores for chest pain,
      heartburn, regurgitation, and dysphagia were similar among the groups (mean range
      1.1-1.35 on a 0-3 scale). Multimodality evaluation changed the diagnosis of GERD
      in 34.5% of cases and led to or guided alternative therapies in 42%. Overlap
      diagnoses were frequent: 10/15 (67%) of patients with eosinophilic esophagitis,
      12/16 (75%) of patients with gastroparesis, and 11/23 (48%) of patients with
      achalasia or dysmotility had concomitant pathologic acid reflux by pH studies.
      Patients with persistent GERD symptoms despite empiric PPI therapy benefit from
      multimodality evaluation that may change the diagnosis and guide therapy in more
      than one third of such cases. Because symptoms are not specific and overlap
      diagnoses are frequent and multifaceted, objective evidence-driven therapies
      should be considered in such patients. 

PMID- 22862423
TI  - Historical contingency and behavioural divergence in territorial Anolis lizards.
AB  - The extent that evolution - including adaptation - is historically contingent
      (dependent on past events) has often been hotly debated, but is still poorly
      understood. In particular, there are little data on the degree that behaviour, an
      aspect of the phenotype that is strongly linked to contemporary environments
      (social or physical), retains the imprint of evolutionary history. In this study,
      I examined whether differences in the design of the territorial displays among
      species of Caribbean Anolis lizards reflect island-specific selection regimes, or
      historically contingent predispositions associated with different clade
      histories. Adult males advertise territory ownership using a series of headbobs
      and dewlap extensions, bouts of which vary in duration among species. When
      display durations were mapped onto the Anolis phylogeny, prominent differences
      between species belonging to the Western and Eastern Caribbean radiations were
      apparent. Statistical analyses confirmed that species differences in the duration
      of headbob displays, and to some extent the duration of dewlap extensions, were
      historically contingent. The unique evolutionary histories of each clade have
      seemingly had a profound effect on the subsequent direction of display evolution
      among descendent taxa. These results combined with those from previous studies on
      these lizards show that past history can have an important impact on the type of
      behaviour exhibited by species today, to the point that adaptive evolution can
      proceed quite differently in lineages originating from different evolutionary
      starting points.

PMID- 22862424
TI  - The p53-dependent expression of frataxin controls 5-aminolevulinic acid-induced
      accumulation of protoporphyrin IX and photo-damage in cancerous cells.
AB  - Mitochondrial frataxin is involved in various functions such as iron homeostasis,
      iron-sulfur cluster biogenesis, the protection from oxidative stress and
      apoptosis and acts as a tumor suppressor protein. We now show that the expression
      of frataxin is stimulated in a p53-dependent manner and prove that frataxin is a
      direct p53 target gene by showing that the p53-responsive element in the promoter
      of the mouse frataxin gene is bound by p53. The bacterial expression of human
      frataxin stimulated maturation of human ferrochelatase, which catalyzes the
      insertion of iron into protoporphyrin at the last step of heme biosynthesis.
      Overexpression of frataxin in human cancer A431 and HeLa cells lowered 5
      aminolevulinic acid(ALA)-induced accumulation of protoporphyrin and induced
      resistance to ALA-induced photo-damage, whereas p53 silencing with siRNA in non
      tumor HEK293T cells down-regulated the expression of frataxin and increased the
      accumulation of protoporphyrin. Thus, the decrease of the expression of frataxin
      unregulated by p53 in tumor cells enhances ALA-induced photo-damage, by down
      regulation of mitochondrial functions.

PMID- 22862425
TI  - Imaging of basal cell carcinoma by high-definition optical coherence tomography:
      histomorphological correlation. A pilot study.
AB  - BACKGROUND: With the continued development of noninvasive therapies for basal
      cell carcinoma (BCC) such as photodynamic therapy and immune therapies,
      noninvasive diagnosis and monitoring become increasingly relevant. High
      definition optical coherence tomography (HD-OCT) is a high-resolution imaging
      tool, with micrometre resolution in both transversal and axial directions,
      enabling visualization of individual cells up to a depth of around 570 MUm, and
      filling the imaging gap between conventional optical coherence tomography (OCT)
      and reflectance confocal microscopy (RCM). OBJECTIVES: We sought to determine the
      feasibility of detecting BCC by this technique using criteria defined for RCM and
      conventional OCT and compared with histology. METHODS: In this pilot study skin
      lesions of 21 patients with a histologically proven BCC were imaged by HD-OCT
      just before excision and images analysed qualitatively. RESULTS: Features for
      four different BCC subtypes were described in both transverse and axial
      directions. In general, these features were subepidermal or intradermal
      aggregations of cells. These islands or trabeculae were surrounded by a less
      refractile border corresponding with palisading and peritumoral mucin production.
      There was a pronounced architectural disarray of the epidermis. A variably
      refractile stroma together with abundant dilated peritumoral blood vessels was
      present. These features were comparable with histological features for each
      patient. CONCLUSIONS: Using features already suggested by RCM and conventional
      OCT, the study implies that HD-OCT facilitates in vivo diagnosis of BCC and
      allows the distinction between different BCC subtypes for increased clinical
      utility.

PMID- 22862426
TI  - Centering as a model for group visits among women with chronic pelvic pain.
AB  - Providing comprehensive care for chronic pelvic pain is impeded by time and
      resource constraints of the standard health care visit. To provide patient
      education, psychosocial support, and health care assessment, we developed group
      visits for women with chronic pelvic pain using an evidence-based, holistic
      nursing approach. In this article, we describe the structure of group visits, the
      process of conducting Centering group visits focused on empowerment, and the
      content of a holistic curriculum for women with chronic pelvic pain. 

PMID- 22862428
TI  - Near-infrared emitting polymer nanogels for efficient sentinel lymph node
      mapping.
AB  - Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic
      spread of primary tumor to regional lymph nodes in clinical practice. In this
      research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a
      hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was
      developed. The NIR-emitting polymer nanoprobes were designed and synthesized by
      conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer
      nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the
      IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG
      into the front paw of a mouse, the nanoprobes entered the lymphatic system and
      migrated to the axillary lymph node within 2 min. The NIR fluorescence signal
      intensity and retention time of NIR-PNG in the lymph node were superior to the
      corresponding properties of the IRDye800-free dye. A immunohistofluorescence
      study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes
      were predominantly co-localized with macrophages and dendritic cells. Intradermal
      injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time
      imaging of the lymphatic flow toward the SLN. The position of the SLN was
      identified within 1 min with the help of the NIR fluorescence images. Taken
      together, the experimental results demonstrating the enhanced photostability and
      retention time of the NIR-PNG provide strong evidence for the potential utility
      of these polymer probes in cancer surgery such as SLN mapping.

PMID- 22862427
TI  - Teaching hospital financial status and patient outcomes following ACGME duty hour
      reform.
AB  - OBJECTIVE: To examine whether hospital financial health was associated with
      differential changes in outcomes after implementation of 2003 ACGME duty hour
      regulations. DATA SOURCES/STUDY SETTING: Observational study of 3,614,174
      Medicare patients admitted to 869 teaching hospitals from July 1, 2000 to June
      30, 2005. STUDY DESIGN: Interrupted time series analysis using logistic
      regression to adjust for patient comorbidities, secular trends, and hospital
      site. Outcomes included 30-day mortality, AHRQ Patient Safety Indicators (PSIs),
      failure-to-rescue (FTR) rates, and prolonged length of stay (PLOS). PRINCIPAL
      FINDINGS: All eight analyses measuring the impact of duty hour reform on
      mortality by hospital financial health quartile, in postreform year 1 ("Post 1")
      or year 2 ("Post 2") versus the prereform period, were insignificant: Post 1 OR
      range 1.00-1.02 and Post 2 OR range 0.99-1.02. For PSIs, all six tests showed
      clinically insignificant effect sizes. The FTR rate analysis demonstrated
      nonsignificance in both postreform years (OR 1.00 for both). The PLOS outcomes
      varied significantly only for the combined surgical sample in Post 2, but this
      effect was very small, OR 1.03 (95% CI 1.02, 1.04). CONCLUSIONS: The impact of
      2003 ACGME duty hour reform on patient outcomes did not differ by hospital
      financial health. This finding is somewhat reassuring, given additional financial
      pressure on teaching hospitals from 2011 duty hour regulations.

PMID- 22862429
TI  - Three dimensional quantification of mandibular bone remodeling using standard
      tessellation language registration based superimposition.
AB  - OBJECTIVE: The aim of this study was to evaluate a new method to quantify
      longitudinal mandibular bone remodeling three-dimensionally by superimposition of
      cone beam computed tomography images. MATERIALS AND METHODS: This method is used
      to quantify the treatment effects of implant-retained overdentures in 20 patients
      aged 52-79 at recruitment after 1 and 2 years post treatment. Three dimensional
      models of pre- and post-treatment were reconstructed for each patient and
      superimposed using Standard Tessellation Language registration method and
      segmentation. RESULTS: Color maps of the differences generated by superimposition
      allow detailed examination and quantification of the progressive dimensional
      changes of bone in a three-dimensional manner and enable the visualization of the
      apical displacement and thinning of the cortical layer of bone underneath the
      denture base. Most of the remodeling changes took place during the first year
      with a mean decrease in volume of 3.7% (SD = 4.4%; range = +3.7% to -15.9%,
      median = -3.7%). This remodeling pattern continued during the second year, but at
      a reduced rate of 2.5% per year (SD = 4.2%; range = +2.1% to -11.3%, median = 
      3.9%). CONCLUSION: Standard Tessellation Language registration based
      superimposition of cone beam computed tomography images may be considered an
      objective and reproducible method to three-dimensionally quantify mandibular bone
      remodeling.

PMID- 22862430
TI  - One week of multifactorial high-stress military ranger training affects Gram
      negative signalling.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4), especially expressed on
      monocytes/macrophages, connects microbial and sterile innate immune activation.
      Lipopolysaccharide (LPS) from Gram-negative bacteria and several endogenous
      molecules, among others saturated fatty acids (SFAs), are able to induce
      signalling through this receptor. Downstream inflammatory cytokines orchestrate
      the immune response. Our aim was to investigate how long-lasting multifactorial
      stress affects Gram-negative signalling and search for possible correlations
      between cytokine production and TLR4 expression or SFA concentration. METHODS:
      Eight healthy males were studied during a 7-day ranger-training course with semi
      continuous physical strain, together with energy and sleep restrictions. Blood
      drawn on days 0, 3, 5 and 7 was incubated ex vivo for 6 h with or without LPS 10
      ng/mL, whereupon surface expression of TLR4 on CD14+ monocytes and supernatant
      concentrations of inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were
      measured. In addition, plasma free fatty acids were quantified. RESULTS: Monocyte
      TLR4 expression was elevated throughout the course (p < 0.05 vs. baseline).
      Corresponding results were found for SFAs. The concentration of TNF-alpha
      increased significantly on day 3 and thereafter normalized, and a similar pattern
      was seen for IL-1beta. No correlations were found between cytokine concentrations
      and monocyte TLR4 expression or plasma SFAs. CONCLUSION: Multifactorial stress
      significantly affected ex vivo production of TNF-alpha and monocyte surface
      expression of TLR4. In addition, mobilization of fat resulted in increased plasma
      concentrations of SFAs. No associations between inflammatory cytokines and
      monocyte TLR4 expression or SFAs were found.

PMID- 22862431
TI  - Regional heterogeneity of systolic dysfunction is associated with ventricular
      dyssynchrony in patients with idiopathic dilated cardiomyopathy and narrow QRS
      complex.
AB  - BACKGROUND: Regional heterogeneity of left ventricular (LV) contraction, known as
      dyssynergy, in idiopathic dilated cardiomyopathy (IDC) patients has been
      previously reported, but no comprehensive analysis of this abnormality has been
      made. The purpose of this study was to test the hypothesis that regional
      heterogeneity of systolic dysfunction is associated with LV dyssynchrony in IDC
      patients with a narrow QRS complex using novel three-dimensional (3D) speckle
      tracking strain. METHODS: We studied 54 consecutive IDC patients with ejection
      fraction (EF) of 34 +/- 12% and QRS duration of 102 +/- 13 msec (all <120 msec),
      and 30 age-matched normal controls. The 3D speckle-tracking LV dyssynchrony (LV
      dyssynchrony index) was quantified from all 16 LV sites to determine the standard
      deviation (SD) of time-to-peak strain. Similarly, regional heterogeneity of LV
      systolic function (LV dyssynergy index) was quantified from all 16 LV sites to
      establish the SD of peak 3D speckle-tracking strain. RESULTS: The LV dyssynergy
      and dyssynchrony indices of IDC patients were significantly larger than those of
      normal controls. Furthermore, IDC patients showed significantly higher Z-scores
      for septum and inferior regions than for the free wall (3.34 +/- 1.21 vs. 1.69 +/
      1.06 and 2.79 +/- 1.30 vs. 1.69 +/- 1.06, respectively, P < 0.001). An important
      findings of multivariable analysis was that the LV dyssynergy index (beta = 0.69,
      P < 0.001) and LVEF (beta = -0.34, P = 0.001) were independent determinants of
      the LV dyssynchrony index. CONCLUSION: 3D speckle-tracking strain revealed that
      the myocardial systolic dysfunction of IDC patients with a narrow QRS complex has
      a marked heterogeneous regional distribution. This regional heterogeneity as well
      as systolic dysfunction is thought to lead to LV dyssynchrony.

PMID- 22862432
TI  - Pneumococcal vaccines for children: a global public health priority.
AB  - Pneumococcal conjugated vaccines have been recommended in children for over a
      decade in many countries worldwide. Here we review the development of
      pneumococcal vaccines with a focus on the two types currently available for
      children and their safety record. We discuss also the effect of vaccines,
      including the 13-valent pneumococcal conjugate vaccine, on invasive pneumococcal
      diseases in children, particularly bacteraemia, pneumonia and meningitis, as well
      as on mucosal disease and carriage. In regions where immunization was implemented
      in young children, the number of invasive pneumococcal diseases decreased
      significantly, not only in the target age group, but also in younger and much
      older subjects. Challenges and future perspectives regarding the development of
      new 'universal' vaccines, which could bypass the current problem of serotype
      specific protection in a context of serotype replacement, are also discussed.

PMID- 22861838
TI  - Search for down-type fourth generation quarks with the ATLAS detector in events
      with one lepton and hadronically decaying W bosons.
AB  - This Letter presents a search for pair production of heavy down-type quarks
      decaying via b' -> Wt in the lepton + jets channel, as b'b' -> W- tW+ t -> bbW+ W
      W+ W- -> l+/- nubbqqqqqq. In addition to requiring exactly one lepton, large
      missing transverse momentum, and at least six jets, the invariant mass of nearby
      jet pairs is used to identify high transverse momentum W bosons. In data
      corresponding to an integrated luminosity of 1.04  fb(-1) from pp collisions at
      sqrt[s] = 7  TeV recorded with the ATLAS detector, a heavy down-type quark with
      mass less than 480 GeV can be excluded at the 95% confidence level.

PMID- 22862433
TI  - Intravenous sulprostone infusion in the treatment of retained placenta.
AB  - OBJECTIVE: To analyze the effectiveness of intravenous sulprostone infusion for
      the treatment of retained placenta without massive primary hemorrhage among women
      at an university hospital over a three-year period. DESIGN: Retrospective
      observational study. SETTING: University teaching hospital. POPULATION: 126
      consecutive women with placental retention and intravenous sulprostone infusion
      as primary treatment performed from October 2007 up to December 2011. METHODS:
      Hospital records of women who received sulprostone infusion to attempt placental
      expulsion were reviewed. MAIN OUTCOME MEASURES: Primary endpoints of the study
      were expulsion of placenta and the total amount of blood loss during delivery.
      RESULTS: The placenta was successfully expelled in 39.7% of cases, whereas 60.3%
      of women underwent manual removal of placenta. Blood loss was significantly lower
      in women with successful placental expulsion than in women who had manual removal
      of the placenta (582 +/- 431 ml vs. 1275 +/- 721 ml, p < 0.0001). Sulprostone
      infusion did not cause adverse effects or significant postpartum morbidity.
      CONCLUSIONS: Intravenous sulprostone infusion is safe and reduces both blood loss
      and the need for manual removal of the placenta.

PMID- 22862434
TI  - Variation in penetration of submicrometric particles through electrostatic
      filtering facepieces during exposure to paraffin oil aerosol.
AB  - Several studies show the increase of penetration through electrostatic filters
      during exposure to an aerosol flow, because of particle deposition on filter
      fibers. We studied the effect of increasing loads of paraffin oil aerosol on the
      penetration of selected particle sizes through an electrostatic filtering
      facepiece. FFP2 facepieces were exposed for 8 hr to a flow rate of 95.0 +/- 0.5
      L/min of polydisperse paraffin aerosol at 20.0 +/- 0.5 mg/m(3). The penetration
      of bis(2-ethylhexyl)sebacate (DEHS) monodisperse neutralized aerosols, with
      selected particle size in the 0.03-0.40 MUm range, was measured immediately prior
      to the start of the paraffin aerosol loading and at 1, 4, and 8 hr after the
      start of paraffin aerosol loading. Penetration through isopropanol-treated
      facepieces not oil paraffin loaded was also measured to evaluate facepiece
      behavior when electrostatic capture mechanisms are practically absent. During
      exposure to paraffin aerosol, DEHS penetration gradually increased for all
      aerosol sizes, and the most penetrating particle size (0.05 MUm at the beginning
      of exposure) shifted slightly to larger diameters. After the isopropanol
      treatment, the higher penetration value was 0.30 MUm. In addition to an increased
      penetration during paraffin loading at a given particle size, the relative degree
      of increase was greater as the particle size increased. Penetration value
      measured after 8 hr for 0.03-MUm particles was on average 1.6 times the initial
      value, whereas it was about 8 times for 0.40-MUm particles. This behavior, as
      well evidenced in the measurements of isopropanol-treated facepieces, can be
      attributed to the increasing action in particle capture of the electrostatic
      forces (Coulomb and polarization), which depend strictly on the diameter and
      electrical charge of neutralized aerosol particles. With reference to
      electrostatic filtering facepieces as personal protective equipment, results
      suggest the importance of complying with the manufacturer instructions when it is
      specified that their use has to be restricted to a single shift.

PMID- 22862541
TI  - A solution-processed trilayer electrochemical device: localizing the light
      emission for optimized performance.
AB  - We present a solution-processed trilayer light-emitting device architecture,
      comprising two hydrophobic and mobile-ion-containing "transport layers"
      sandwiching a hydrophilic and ion-free "intermediate layer", which allows for
      lowered self-absorption, minimized electrode quenching, and tunable light
      emission. Our results reveal that the transport layers can be doped in situ when
      a voltage is applied, that the intermediate layer as desired can contribute
      significantly to the light emission, and that the key to a successful operation
      is the employment of a porous and (~5-10 nm) thin intermediate layer allowing for
      facile ion transport. We report that such a solution-processed device, comprising
      a thick trilayer material (~250 nm) and air-stable electrodes, emits blue light
      (lambda(peak) = 450, 484 nm) with high efficiency (5.3 cd/A) at a low drive
      voltage of 5 V.

PMID- 22862543
TI  - Lost papers (5).

PMID- 22862544
TI  - Stable isotope terminology. 1983.

PMID- 22862542
TI  - Beyond warmth and conflict: the developmental utility of a boundary
      conceptualization of sibling relationship processes.
AB  - Translating relationship boundaries conceptualizations to the study of sibling
      relationships, this study examined the utility of sibling enmeshment and
      disengagement in predicting child adjustment difficulties in a sample of 282
      mothers and adolescents (mean age=12.7 years). Mothers completed a semistructured
      interview at the first measurement occasion to assess sibling interaction
      patterns. Adolescents, mothers, and teachers reported on children's adjustment
      problems across 2 annual waves of assessment. Supporting the incremental utility
      of a boundary conceptualization of sibling relationships, results of latent
      difference score analyses indicated that coder ratings of sibling enmeshment and
      disengagement uniquely predicted greater adolescent adjustment difficulties even
      after taking into account standard indices of sibling relationship quality (i.e.,
      warmth and conflict) and sibling structural characteristics (e.g., sex).

PMID- 22862545
TI  - H-D exchange on graphite-potassium intercalation compounds. 1991.

PMID- 22862546
TI  - Case-control study of Staphylococcus lugdunensis infection isolates from small
      companion animals.
AB  - BACKGROUND: Coagulase-negative Staphylococcus lugdunensis has recently been shown
      to cause invasive infections of people, which are similar in pathogenic effect to
      those caused by Staphylococcus aureus. Little is known about the pathogenicity of
      S. lugdunensis in companion animals. OBJECTIVES: To compare potential risk
      factors for infection, body sites affected, and whether cases and controls had
      been treated with antimicrobial drugs based upon susceptibility test results.
      ANIMALS: Thirty-three cases of S. lugdunensis infection (25 dogs, six cats and
      two small mammals) were identified between January 2003 and August 2011. Two
      Staphylococcus pseudintermedius controls, which were identified by the
      microbiology laboratory immediately before and after each S. lugdunensis case,
      were host-species matched to each case. METHODS: A retrospective case-control
      analysis. RESULTS: During the period evaluated, the prevalence of S. lugdunensis
      infection was 1.3 cases per 10,000 hospital admissions for dogs and 0.95 cases
      per 10,000 admissions for cats (P = 0.453). In univariate analyses, S.
      pseudintermedius isolation was significantly associated with skin infections (P <
      0.0001), while S. lugdunensis isolation was associated with the respiratory tract
      (P = 0.03) and other deep tissues (P = 0.005). Cases were less likely than
      controls to have been treated based upon susceptibility test results (P = 0.02).
      A conditional logistic regression analysis showed isolation of S. lugdunensis to
      be associated with recent (<= 30 days) steroid administration (odds ratio, 17.72;
      95% confidence interval, 2.35-132.82; P = 0.005); and in-patient status (odds
      ratio, 9.67; 95% confidence interval, 2.18-42.88; P = 0.003). CONCLUSIONS: These
      results suggest that S. lugdunensis may cause invasive infections in companion
      animals, which should be treated with antimicrobials based upon susceptibility
      tests when available.

PMID- 22862547
TI  - The psycho-social dimension of pain and health-related quality of life in the
      oldest old.
AB  - BACKGROUND: Chronic pain has an impact on the physical and social functioning of
      older people which in turn may worsen their health-related quality of life.
      Research with focus on prolonged extensive pain in the most elderly and how pain
      may interfere with their life situation is scarce. AIMS:   The aims were to
      describe and investigate pain from a multidimensional point of view (duration,
      location, psycho-social) and health-related quality of life as well as to compare
      sex and age groups in people aged 80 years and over. METHODS: In this cross
      sectional study, a total of 225 of 282 people responded to a questionnaire
      consisting of two instruments and background questions. The psycho-social
      dimension of pain was measured using the Multidimensional Pain Inventory-Swedish
      language version (MPI-S) with five scales: Pain Severity, Interference, Life
      Control, Affective Distress and Social Support. Health-related quality of life
      was measured using the Short Form Health Survey-12 (SF-12). RESULTS: Median
      duration of pain was 9.0 years, and the mean number of pain locations was 2.04.
      The MPI-S scale Interference with a negative orientation had the highest mean
      score, while the mean score for Social Support was the highest for the scales
      with a positive orientation. The duration of pain was significantly greater for
      women, and those aged 80-85 years had higher pain severity than those aged>=86.
      Participants with a lower health-related quality of life experienced
      significantly more severe pain, were more troubled with pain and had less control
      of their life. CONCLUSIONS: Older people with prolonged pain suffered from a low
      health-related quality of life. Pain interfered with their lives and contributed
      to diminished control in their daily lives. Nurses are essential for the
      identification and prevention of pain and should be aware of how pain affects
      older people's physical, mental and social health.

PMID- 22862548
TI  - National estimates of pubertal milestones among urban and rural Chinese boys.
AB  - AIM: To provide up-to-date pubertal characteristics in a representative
      population of boys from both urban and rural areas of China. SUBJECTS AND
      METHODS: The China Puberty Research Collaboration enrolled 15 011 boys of Chinese
      Han ethnicity aged 6.0-18.9 years in eight regions including both urban and rural
      areas. Stages of genital and pubic hair development were assessed by trained
      physicians according to the Tanner method. Testicular volume was evaluated with a
      Prader orchidometer. RESULTS: Median age for onset of testicular volume of 4 mL
      or greater was 11.02 years. Median age for onset of genital (G2), pubic hair
      development (PH2) and spermarche was 11.24 years, 12.67 years and 14.32 years,
      respectively. Boys with BMI >= 85th percentile reached the onset of TV >= 4 ml
      (11.09 years), G2 (11.34 years) and G3 (13.01 years) later than boys with a
      normal BMI (10.95 years, 11.1 years and 12.88 years, respectively). Urban boys
      achieved pubertal milestones at an earlier age than rural peers except for G5
      (13.4 vs 13.76 years) and PH5 (12.86 years vs 13.14 years). CONCLUSIONS: There is
      an asynchronous pattern in the onset of puberty among Chinese boys. Higher BMI is
      related to early pubertal onset but fast pubertal progression. Urban boys
      achieved onset of puberty earlier than rural boys in China.

PMID- 22862549
TI  - Ultrasound-guided supraclavicular cannulation of the brachiocephalic vein in
      infants: a retrospective analysis of a case series.
AB  - BACKGROUND: In this study, we analyze the impact of the choice of either the left
      or right brachiocephalic vein (BCV) on the cannulation success when using the
      ultrasound-guided supraclavicular in-plane technique approach to the
      longitudinally viewed BCV in infants. METHODS: The central vascular protocols of
      183 infants were reviewed retrospectively. RESULTS: The weight ranged from 0.7 to
      10 kg. Central venous catheter placement was eventually successful in 98.9%. In
      141 patients (82.9%), the left BCV was successfully punctured on the first
      attempt, in 23 patients (13.5%) after 2 and in 6 patients (3.5%) after 3
      attempts. The right BCV was successfully punctured on the first attempt in five
      patients (38.4%), in three patients (15.3%) after two and in five patients
      (38.4%) after three attempts, respectively. Significantly more puncture attempts
      were required for the right BCV (chi-square analysis: P < 0.01). There was also a
      significant improvement of the success rate over the time course of the case
      series (Jonckheere-test: P < 0.01). CONCLUSION: It seems to be easier to
      cannulate the left BCV than the right BCV when using this ultrasound-guided
      supraclavicular strict in-plane technique. Gaining experience with this method
      seems to improve the cannulation success.

PMID- 22862550
TI  - Adsorption of insecticidal Cry1Ab protein to humic substances. 2. Influence of
      humic and fulvic acid charge and polarity characteristics.
AB  - Assessing the fate and potential risks of transgenic Cry proteins in soils
      requires understanding of Cry protein adsorption to soil particles. The companion
      paper provided evidence that patch-controlled electrostatic attraction (PCEA) and
      the hydrophobic effect contributed to Cry1Ab protein adsorption to an apolar
      humic acid (HA). Here, we further assess the relative importance of these
      contributions by comparing Cry1Ab adsorption to seven humic substances varying in
      polarity and charge, at different solution pH and ionic strength, I. Cry1Ab
      adsorption to relatively apolar HAs at I = 50 mM exhibited rapid initial rates,
      was extensive, and was only partially reversible at pH 5-8, whereas adsorption to
      more polar fulvic acids was weak and reversible or absent at pH >6. The decrease
      in adsorption with increasing HS polarity at all tested pH strongly supports a
      large contribution from the hydrophobic effect to adsorption, particularly at I =
      50 mM when PCEA was effectively screened. Using insect bioassays, we further show
      that Cry1Ab adsorbed to a selected HA retained full insecticidal activity. Our
      results highlight the need to consider adsorption to soil organic matter in
      models that assess the fate of Cry proteins in soils.

PMID- 22862551
TI  - Calcium and salinity as selective factors in plate morph evolution of the three
      spined stickleback (Gasterosteus aculeatus).
AB  - Identifying the causal factors underlying natural selection remains a key
      challenge in evolutionary biology. Although the genetic basis for the plate morph
      evolution of three-spined stickleback (Gasterosteus aculeatus) is well described,
      the environmental variables that form the basis for different morphs are not
      understood. We measured the effects of dissolved calcium and salinity on the
      growth of sticklebacks with different plate morphs from Scotland and Poland.
      There was a significant interaction of calcium with plate morph for fish from
      both regions, with complete morph sticklebacks growing more slowly at low calcium
      concentrations and low morph sticklebacks showing divergent responses to calcium
      concentration. A Scottish anadromous population showed evidence of local
      adaptation to high salinity, which was independent of plate morph. Polish and
      Scottish populations diverged in their response to salinity, suggesting a
      difference in osmotic regulation. The results implicate a role for calcium in
      selecting for plate morph evolution in sticklebacks, possibly as a limiting
      element in skeletal growth.

PMID- 22862553
TI  - The intensity of immune activation is linked to the level of  CCR5 expression in
      human immunodeficiency virus type  1-infected persons.
AB  - Immune activation is a main driver of AIDS- and non-AIDS-linked morbidities in
      the course of HIV-1 infection. As CCR5, the main HIV-1 co-receptor, is not only a
      chemokine receptor but also a co-activation molecule expressed at the surface of
      T cells, it could be directly involved in this immune activation. To test this
      hypothesis, we measured by flow cytometry the mean number of CCR5 molecules at
      the surface of non-activated CD4(+) T cells (CCR5 density), which determines the
      intensity of CCR5 signalling, and the percentage of CD8(+) T cells over
      expressing CD38 (CD38 expression), a major marker of immune activation, in the
      blood of 67 HIV-1-infected, non-treated individuals. CCR5 density was correlated
      with CD38 expression independently of viral load (P=0.016). CCR5 density remained
      unchanged after highly active anti-retroviral therapy (HAART) introduction or
      cessation, whereas CD38 expression decreased and increased, respectively.
      Moreover, pre-therapeutic CCR5 density was highly predictive (r=0.736, P<10(-4) )
      of residual CD38 over-expression after 9 months of HAART. Hence, CCR5 might play
      an immunological role in HIV-1 infection as a driver of immune activation. This
      could explain why CCR5 antagonists may have an inhibitory effect on immune
      activation.

PMID- 22862555
TI  - IL36RN gene mutations are not associated with sporadic generalized pustular
      psoriasis in Chinese patients.

PMID- 22862554
TI  - 5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1
      and vascular cell adhesion molecule 1 via the Akt and nuclear factor-kappaB
      dependent pathway, leading to suppression of adhesion of monocytes and
      eosinophils to bronchial epithelial cells.
AB  - 5,7-Dihydroxy-3',4',6'-trimethoxyflavone (eupatilin), the active pharmacological
      ingredient from Artemisia asiatica Nakai (Asteraceae), is reported to have a
      variety of anti-inflammatory properties in intestinal epithelial cells. However,
      little information is known about the molecular mechanism of eupatilin-induced
      attenuation of bronchial epithelial inflammation. This study investigates the
      role of eupatilin in the adhesion of inflammatory cells such as monocytes and
      eosinophils to bronchial epithelial cells. Stimulation of a human bronchial
      epithelial cell line (BEAS-2B) with tumour necrosis factor-alpha (TNF-alpha)
      increased the expression of surface adhesion molecules, including intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in
      which eupatilin significantly inhibited the expression of those adhesion
      molecules in a dose-dependent manner. Eupatilin suppressed the TNF-alpha-induced
      activation of IkappaBalpha and nuclear factor-kappaB (NF-kappaB) signals in BEAS
      2B cells. The IkappaB kinase (IKK) activation was also significantly reduced in
      eupatilin-pre-treated BEAS-2B and primary normal human bronchial epithelial
      (NHBE) cells. However, eupatilin did not influence AP-1 activity in TNF-alpha
      stimulated cells. Suppression of NF-kappaB signalling induced by eupatilin
      resulted in the inhibition of the expression of adhesion molecules and the
      adhesion of monocytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin
      suppressed the phosphorylation of Akt in TNF-alpha-stimulated BEAS-2B and NHBE
      cells, leading to down-regulation of NF-kappaB activation and adhesion molecule
      expression and finally to suppression of the inflammatory cell adhesion to
      epithelial cells. These results suggest that eupatilin can inhibit the adhesion
      of inflammatory cells to bronchial epithelial cells via a signalling pathway,
      including activation of Akt and NF-kappaB, as well as expression of adhesion
      molecules.

PMID- 22862556
TI  - Characterization of a smartphone camera's response to ultraviolet A radiation.
AB  - As part of a wider study into the use of smartphones as solar ultraviolet
      radiation monitors, this article characterizes the ultraviolet A (UVA; 320-400
      nm) response of a consumer complementary metal oxide semiconductor (CMOS)-based
      smartphone image sensor in a controlled laboratory environment. The CMOS image
      sensor in the camera possesses inherent sensitivity to UVA, and despite the
      attenuation due to the lens and neutral density and wavelength-specific bandpass
      filters, the measured relative UVA irradiances relative to the incident
      irradiances range from 0.0065% at 380 nm to 0.0051% at 340 nm. In addition, the
      sensor demonstrates a predictable response to low-intensity discrete UVA stimuli
      that can be modelled using the ratio of recorded digital values to the incident
      UVA irradiance for a given automatic exposure time, and resulting in measurement
      errors that are typically less than 5%. Our results support the idea that
      smartphones can be used for scientific monitoring of UVA radiation.

PMID- 22862557
TI  - Emergency contraception.

PMID- 22862552
TI  - Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to
      autoimmunity.
AB  - More than half of the known protein tyrosine phosphatases (PTPs) in the human
      genome are expressed in T cells, and significant progress has been made in
      elucidating the biology of these enzymes in T-cell development and function. Here
      we provide a systematic review of the current understanding of the roles of PTPs
      in T-cell activation, providing insight into their mechanisms of action and
      regulation in T-cell receptor signalling, the phenotypes of their genetically
      modified mice, and their possible involvement in T-cell-mediated autoimmune
      disease. Our projection is that the interest in PTPs as mediators of T-cell
      homeostasis will continue to rise with further functional analysis of these
      proteins, and PTPs will be increasingly considered as targets of immunomodulatory
      therapies.

PMID- 22862558
TI  - Active ingredients of traditional Chinese medicine in the treatment of diabetes
      and diabetic complications.
AB  - INTRODUCTION: Diabetes mellitus (DM) is a chronic progressive systemic disease
      caused by metabolic disorder. In recent years, significant amounts of studies
      have shown that traditional Chinese medicine (TCM) and its active ingredients
      have obvious hypoglycemic effect. AREAS COVERED: This paper summarizes single
      herbs and their active ingredients from TCM with the role of treating DM, and
      relevant literatures published in the past decades are reviewed. The active
      ingredients are divided into polysaccharides, saponins, alkaloids, flavonoids,
      terpenoids and others, which are described in this article from the aspects of
      active ingredients, sources, models, efficacy, and mechanisms. EXPERT OPINION:
      Mechanisms of TCM in treating DM are concluded: i) to promote insulin secretion
      and increase serum insulin levels; ii) to increase the sensitivity of insulin and
      improve its resistance; iii) to inhibit glucose absorption; iv) to affect glucose
      metabolism of insulin receptor; and v) to scavenge radicals and prevent lipid
      peroxidation. The separation and extraction of effective monomer from TCM is an
      important direction of anti-diabetic drug discovery currently. Future research
      about hypoglycemic mechanism of TCM based on the clinical should combine with
      modern scientific methods and regulatory approach to strive for more meaningful
      discovery and innovation.

PMID- 22862559
TI  - Cardioprotective effects of ozone oxidative preconditioning in an in vivo model
      of ischemia/reperfusion injury in rats.
AB  - BACKGROUND: Several studies have demonstrated the beneficial effects of ozone
      oxidative preconditioning in several pathologies characterized by cellular
      oxidative and inflammatory burden. The present study was designed to investigate
      the cardioprotective effects of oxidative preconditioning in ischemia/reperfusion
      (I/R) injury. METHODS: Rats were randomly assigned into five groups. Groups 1 and
      2 were normal and I/R groups, respectively. Two of the other groups received two
      different doses of ozone therapies by rectal insufflations. The last group
      received vehicle (oxygen). Rats were subjected to myocardial I/R (40 min/10 min).
      Heart rate and ventricular arrhythmias were recorded during I/R progress. At the
      end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total
      nitrate/nitrite (NO(x)) were determined. In addition, lactate, adenine
      nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione
      (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left
      ventricle. Histological examination was also performed to visualize the
      protective cellular effects. RESULTS: Both doses of ozone therapy were equally
      protective in reducing CK-MB release. However, the higher dose was more effective
      in reducing oxidative stress, lactate accumulation, elevated MPO activity and
      plasma NO(x) as well as preserving myocardial adenine nucleotides. Histological
      examination also revealed better improvement with a higher dose of ozone therapy
      compared to the I/R group. CONCLUSION: Ozone therapy can afford significant
      cardioprotection against biochemical and histological changes associated with I/R
      injury.

PMID- 22862560
TI  - Investigation of the Mg-HCO3--ATPase activity of thyroid tissue cells under
      various pathologies.
AB  - Distribution of the Mg2+-dependent, HCO3--stimulated ATPase (HCO3--ATPase) was
      investigated in sub-cellular fractions of the tissue of the human thyroid gland.
      It was found that especially high enzymatic activity is characteristic of
      mitochondria and the endoplasmic reticulum. Correlation between various
      pathologies of the thyroid and HCO3--ATPase activity was demonstrated. The
      activity was evaluated using the difference between active and passive ATPase.
      During development of the various pathologies, the sub-cellular fractions of the
      gland showed uneven alterations of HCO3--ATPase activity. Intriguingly, the
      enzyme kinetic parameters are also changed, i.e. in the different pathologies
      both enzyme activity and its affinity towards bicarbonate ions are altered. This
      raises the question whether pathology is caused by, or results in, changes in the
      enzyme at the molecular level.

PMID- 22862562
TI  - Tenside-free preparation of nanogels with high functional beta-cyclodextrin
      content.
AB  - We present the preparation of ultrafine (R(h), 50 -150 nm) nanogels through
      tenside-free condensation of reactive prepolymers with beta-cyclodextrin (beta
      CD) in water. These nanogels possess a maximum content of 60 wt % functional beta
      CD that can form inclusion complexes as demonstrated by dye sorption with
      phenolphthalein. Aside of this extremely high uptake capacity to hydrophobic
      molecules, the nanogels also show good adhesion to surfaces in homogeneous
      distribution with size of R(h) of 25 nm under dry conditions.

PMID- 22862561
TI  - APOE genotype affects the pre-synaptic compartment of glutamatergic nerve
      terminals.
AB  - Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer's disease and
      other conditions of brain damage. Using APOE knock-in mice, we have previously
      shown that APOE-epsilon4 Targeted Replacement (TR) mice have fewer dendritic
      spines and reduced branching in cortical neurons. As dendritic spines are post
      synaptic sites of excitatory neurotransmission, we used APOE TR mice to examine
      whether APOE genotype affected the various elements of the glutamate-glutamine
      cycle. We found that levels of glutamine synthetase and glutamate uptake
      transporters were unchanged among the APOE genotypes. However, compared with APOE
      epsilon3 TR mice, APOE-epsilon4 TR mice had decreased glutaminase levels (18%, p
      < 0.05), suggesting decreased conversion of glutamine to glutamate. APOE-epsilon4
      TR mice also had increased levels of the vesicular glutamate transporter 1 (20%,
      p < 0.05), suggesting that APOE genotype affects pre-synaptic terminal
      composition. To address whether these changes affected normal neurotransmission,
      we examined the production and metabolism of glutamate and glutamine at 4-5
      months and 1 year. Using high-frequency (13)C/(1)H nuclear magnetic resonance
      spectroscopy, we found that APOE-epsilon4 TR mice have decreased production of
      glutamate and increased levels of glutamine. These factors may contribute to the
      increased risk of neurodegeneration associated with APOE-epsilon4, and also act
      as surrogate markers for Alzheimer's disease risk.

PMID- 22862563
TI  - Effects of oral rehydration and external cooling on physiology, perception, and
      performance in hot, dry climates.
AB  - Only limited research evaluates possible benefits of combined drinking and
      external cooling (by pouring cold water over the body) during exercise.
      Therefore, this study examined cold water drinking and external cooling on
      physiological, perceptual, and performance variables in hot, dry environments.
      Ten male runners completed four trials of walking 90 min at 30% VO(2max) followed
      by running a 5-km time trial in 33 +/- 1  degrees C and 30 +/- 4% relative
      humidity. Trials examined no intervention (CON), oral rehydration (OR), external
      cooling (EC), and oral rehydration plus external cooling (OR + EC). Investigators
      measured rectal temperature, skin temperatures, heart rate, thirst, thermal
      sensation, and ratings of perceived exertion (RPE). Oral rehydration (OR and OR +
      EC) significantly lowered heart rate (P < 0.001) and thirst (P < 0.001) compared
      with nondrinking (CON and EC) during low-intensity exercise. External cooling (EC
      and OR + EC) significantly reduced chest and thigh temperature (P < 0.001),
      thermal sensation (P < 0.001), and RPE (P = 0.041) compared with non-external
      cooling (CON and OR) during low-intensity exercise. Performance exhibited no
      differences (CON = 23.86 +/- 4.57 min, OR = 22.74 +/- 3.20 min, EC = 22.96 +/-
      3.11 min, OR + EC = 22.64 +/- 3.73 min, P = 0.379). Independent of OR, pouring
      cold water on the body benefited skin temperature, thermal sensation, and RPE
      during low-intensity exercise in hot, dry conditions but failed to influence high
      intensity performance.

PMID- 22862564
TI  - Diversity of yeast species during fermentative process contributing to Chinese
      Maotai-flavour liquor making.
AB  - AIMS: The famous traditional Chinese Maotai-flavour liquor is produced by a
      unique spontaneous simultaneous saccharification and fermentation process, which
      contributes to a distinctive yeast community with specific physiological
      properties and performances. Therefore, it would be useful to investigate this
      yeast community and reveal the novelty of its characteristics. METHODS AND
      RESULTS: Nine yeast species were obtained from the fermentation period. A
      combination of physiological and functional analyses revealed a very high
      diversity of yeast populations. In particular, the extremely high temperature and
      low acidity of the fermentation conditions led to an accumulation of species with
      distinctive heat- and acid-resistant properties. Moreover, these yeast species
      were also significant flavour contributors, for various alcohols, acids and
      esters. CONCLUSIONS: The Chinese Maotai-flavour liquor-fermentation process is
      rich in yeast resources with distinctive fermentation properties, which were
      different from other beverages. SIGNIFICANCE AND IMPACT OF THE STUDY: This work
      is the first to study the complex yeast ecology of the Maotai-flavour liquor
      making process. It allows a deeper insight into the mechanism of this process.

PMID- 22862565
TI  - The spread of vaccine-preventable diseases by international travellers: a public
      health concern.
AB  - Vaccine-preventable diseases (VPDs) are costly at both the individual and
      societal levels. The most common VPDs recorded in travellers are enteric (typhoid
      or paratyphoid B) fever, acute viral hepatitis, influenza, varicella, measles,
      pertussis and bacterial meningitis. Travellers suffering from VPDs are frequently
      hospitalized, illustrating the point that VPDs are serious and expensive. Many
      travellers are not properly immunized before travel. In addition to individual
      consequences, VPDs can have public-health consequences if they are introduced or
      re-introduced by infected travellers returning to areas with susceptible
      populations. The international spread of poliomyelitis, Neisseria meningitidis
      serogroup W135 meningococcal infections, measles and influenza provides strong
      evidence of the role of international travel in the globalization of VPDs. The
      surveillance of the emergence, re-emergence or spread of VPDs is essential to
      adapt pre-travel advice and the responses to the VPD.

PMID- 22862671
TI  - Escalation of intake under intermittent ethanol access in diverse mouse
      genotypes.
AB  - Experimental animals offered continuous 24-hour free choice access to ethanol
      rarely display voluntary ethanol consumption at levels sufficient to induce
      intoxication or to engender dependence. One of the simplest ways to increase
      voluntary ethanol intake is to impose temporal limitations on ethanol
      availability. Escalation of ethanol intake has been observed in both rats and
      mice under a variety of different schedules of alternating ethanol access and
      deprivation. Although such effects have been observed in a variety of rat and
      mouse genotypes, little is known concerning possible genetic correlations between
      responses to intermittent ethanol access and other ethanol-related phenotypes. In
      the present study, we examined the effects of intermittent ethanol access in
      mouse genotypes characterized by divergent responses to ethanol in other domains,
      including ethanol preference (C57BL/6J and C3H/HeJ mice), binge-like ethanol
      drinking (High Drinking in the Dark and HS/Npt mice) and ethanol withdrawal
      severity (Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice).
      Although intermittent ethanol access resulted in escalated ethanol intake in all
      tested genotypes, the robustness of the effect varied across genotypes. On the
      other hand, we saw no evidence that the effects of intermittent access are
      correlated with either binge-like drinking or withdrawal severity, and only weak
      evidence for a genetic correlation with baseline ethanol preference. Thus, these
      different ethanol-related traits appear to depend on largely unique sets of
      genetic mediators.

PMID- 22862672
TI  - Comparison of three segmental multifrequency bioelectrical impedance techniques
      in healthy adults.
AB  - BACKGROUND: The analysis of segmental or limb bioimpedance has gained importance
      in human population biology. However, standardized measurement techniques are
      needed. AIM: This study compared three techniques for segmental analysis (T1,
      conventional electrode measurement; T2, use of a novel additional switching unit;
      T3, equipotentials instead of switching unit) which are often used in population
      biology. SUBJECTS AND METHODS: The techniques were compared in 124 healthy adults
      (19-83 years) using a tetrapolar bioimpedance analyser (Nutriguard-M) at multiple
      frequencies (5, 50, 100 kHz) to gain whole-body and segmental resistances,
      reactances and phase angles. RESULTS: Repeated measures ANOVA yielded a
      significant technique effect for most variables (26/27), a significant
      interaction technique *  sex for half (13/27), and a significant interaction
      technique *  age for a quarter (7/27) of variables. CONCLUSIONS: Differences
      exist between the three techniques which are primarily caused by inconsistent
      current pathways. A comparison with literature data showed that, in addition,
      subject's posture during measurement, electrode contact and electrode site may
      lead to inconsistent resistance and reactance values. This makes comparisons
      between different populations difficult. Therefore, this study recommends
      generally using the T2 technique which is standardized, easy to use and, thereby,
      well suited for field studies in large population groups.

PMID- 22862673
TI  - Maternal cell-free messenger RNA in twin pregnancies: the effects of chorionicity
      and severe twin to twin transfusion syndrome (TTTS).
AB  - OBJECTIVE: To investigate the effects of chorionicity and severe twin to twin
      transfusion (TTTS) on maternal circulating cell-free messenger RNA (cf-mRNA).
      DESIGN: Prospective cohort study. SETTING: A UK tertiary referral Fetal Medicine
      Center. POPULATION: All monochorionic (MC) twins complicated by severe TTTS (n=
      23) and a cohort of uncomplicated dichorionic (DC) (n= 10) and MC (n= 7)
      pregnancies, between October 2006 and December 2007. METHODS: Maternal cf-mRNA
      encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH), vascular endothelial
      growth factor receptor 1(VEGFR-1(Flt-1)), vascular endothelial growth factor A
      (VEGF-A), Endoglin, placental growth factor (PlGF), tyrosine kinase with
      immunoglobulin-like and EGF-like domains 1 (Tie-1), angiopoietin 1 (Ang-1) and
      angiopoietin 2 (Ang-2) were measured by a quantitative two-step real-time PCR
      assay after extraction from maternal plasma. RESULTS: The amounts of cf-mRNA
      detectable are reported for uncomplicated DC, MC and TTTS pregnancies,
      respectively: GAPDH - 80, 100 and 96%; VEGFR-1 - 10, 0 and 26%; VEGF-A- 80, 71
      and 96%; Endoglin-70, 71 and 91%; PlGF-70, 57, 26%; Tie-1 0, 43, 0%; Ang-1 71, 50
      and 60% and Ang-2 83, 50 and 89%. There was a significant difference in VEGF-A
      (medians DC -337.3, MC - 390.8, TTTS - 618.6 copies/mL plasma p= 0.024), Endoglin
      (medians DC-14.49, MC-1171, TTTS - 2896 copies/mL plasma p= 0.027) and Ang-2
      (medians DC-13.66, MC-8.49, TTTS 44.80 copies/mL plasma p= 0.007). CONCLUSION:
      Maternal cf-mRNA could be reliably detected for GAPDH, PlGF, VEGF-A, Endoglin,
      Ang-1 and Ang-2 in twin pregnancies and a significant difference was demonstrated
      in VEGF-A, Endoglin and Ang-2 between uncomplicated twins and MC twin pregnancies
      complicated by TTTS. If such alterations in maternal cf-mRNA precede the onset of
      clinically apparent disease, this may be used as an adjuvant blood test to
      complement ultrasound screening.

PMID- 22862674
TI  - Parachute tricuspid valve in a patient with atrial septal defect detected by two-
      and three-dimensional echocardiography.
AB  - Atrioventricular valve parachute deformity was generally seen in the mitral
      position, which is called parachute mitral valve. Parachute deformity is also
      seen in the tricuspid position, but this has rarely been reported as sporadic
      cases. All of these cases were associated with other congenital defects, such as
      double outlet right ventricle, left to right shunt. We herein present two- and
      three-dimensional echocardiographic features of a parachute tricuspid valve in a
      patient with atrial septal defect and prominent eustachian valve. 

PMID- 22862675
TI  - Probiotics in neonatology.
AB  - Probiotics are micro-organisms that confer health benefits on the host.
      Postulated mechanisms include: increasing resistance of the mucosal barrier to
      migration of bacteria and their toxins by strengthening intestinal cell
      junctions, modification of host response to microbial products, augmentation of
      immunoglobulin A mucosal responses, enhancement of enteral nutrition to inhibit
      the growth of pathogens; production of antimicrobial proteins; and competitive
      exclusion of potential pathogens. Published meta-analyses and systematic reviews
      report the effects of probiotics on important clinical outcomes in neonates. This
      paper will review the evidence for probiotic supplementation in neonatology, with
      a focus on preterm infants.

PMID- 22862676
TI  - Photoresists as a high spatial resolution autoradiography substrate for
      quantitative mapping of intra- and sub-cellular distribution of Auger electron
      emitting radionuclides.
AB  - PURPOSE: To explore poly(methyl methacrylate) (PMMA950) as an autoradiography
      substrate. MATERIALS AND METHODS: PMMA950 was spin coated onto a silicon
      substrate. Resists were exposed to either a 25 or 50 keV electron beam (e-beam)
      with fluences of 0.1-33.6 MUC/cm(2). The resulting patterns were analyzed by
      atomic force microscopy (AFM). The dependence of pattern sensitivity and
      resolution on resist thickness, development time and electron energy was
      evaluated and correlated with Monte Carlo (MC) modeling. Conventional micro
      autoradiography (MAR) images were compared to AFM images of photoresist patterns
      obtained following exposure from (111)In-diethylenetriaminepentaacetic acid
      (DTPA)-human epidermal growth factor (hEGF) (4-6 MBq/MUg, 40 nM DTPA-hEGF)
      treated human breast cancer cells MDA-MB-468. RESULTS: MC simulation results
      confirmed the similarity of particle transport in PMMA950 exposed to either an
      (111)In point source or a 25 keV e-beam. Sensitivity was inversely related to
      resist thickness. Development conditions of the resists greatly affected image
      quality. Sensitivity of PMMA950 was similar to the UVIIITM resist (consisting of
      a copolymer of 4-hydroxystyrene and t- butylacrylate) at low electron fluence for
      both 25 and 50 keV e-beam exposure. AFM evaluation of the exposure patterns from
      (111)In-DTPA-hEGF treated cells and nuclei provides more detailed information in
      comparison with that from MAR. CONCLUSIONS: Photoresist autoradiography can
      provide information on both the distribution of radiation sources and their
      strengths within a biological sample; however, the choice of photoresist material
      and processing conditions greatly affects the outcome.

PMID- 22862677
TI  - Potential implication of activating killer cell immunoglobulin-like receptor and
      HLA in onset of pulmonary tuberculosis.
AB  - Killer cell immunoglobulin-like receptor (KIR) and human leucocyte antigen (HLA)
      play crucial role in maintaining immune homoeostasis and controlling immune
      responses. To investigate the influence of KIR and HLA-C ligands on the risk of
      pulmonary tuberculosis (PTB), we studied 200 patients who were confirmed to have
      PTB and 200 healthy controls on the different frequencies of KIR and HLA-C
      ligands. Genotyping of these genes was conducted by sequence-specific primer
      polymerase chain reaction (SSP-PCR) method. Gene frequencies were compared
      between PTB group and the control group by chi(2) test, and P < 0.05 was regarded
      as statistically significant. As a result, the frequency of KIR genotype A/B was
      increased in PTB than controls but A/A was decreased. Moreover, striking
      differences were observed in the frequencies of HLA-Cw*08 between the two groups.
      Besides, the frequencies of '2DL2/3 with C1' in PTB were increased compared with
      control group. In addition, individuals with no KIR2DS3 and no Cw*08 were higher
      in controls than in PTB. KIR2DS1 was increased in PTB when HLA-C group 2 alleles
      were missing. In conclusion, KIR and HLA-C gene polymorphisms were related to
      susceptibility to PTB.

PMID- 22862678
TI  - Highly luminescent and thermally stable lanthanide coordination polymers designed
      from 4-(dipyridin-2-yl)aminobenzoate: efficient energy transfer from Tb3+ to Eu3+
      in a mixed lanthanide coordination compound.
AB  - Herein, a new aromatic carboxylate ligand, namely, 4-(dipyridin-2-yl)aminobenzoic
      acid (HL), has been designed and employed for the construction of a series of
      lanthanide complexes (Eu(3+) = 1, Tb(3+) = 2, and Gd(3+) = 3). Complexes of 1 and
      2 were structurally authenticated by single-crystal X-ray diffraction and were
      found to exist as infinite 1D coordination polymers with the general formulas
      {[Eu(L)(3)(H(2)O)(2)]}(n) (1) and {[Tb(L)(3)(H(2)O)].(H(2)O)}(n) (2). Both
      compounds crystallize in monoclinic space group C2/c. The photophysical
      properties demonstrated that the developed 4-(dipyridin-2-yl)aminobenzoate ligand
      is well suited for the sensitization of Tb(3+) emission (Phi(overall) = 64%)
      thanks to the favorable position of the triplet state ((3)pipi*) of the ligand
      [the energy difference between the triplet state of the ligand and the excited
      state of Tb(3+) (DeltaE) = (3)pipi* - (5)D(4) = 3197 cm(-1)], as investigated in
      the Gd(3+) complex. On the other hand, the corresponding Eu(3+) complex shows
      weak luminescence efficiency (Phi(overall) = 7%) due to poor matching of the
      triplet state of the ligand with that of the emissive excited states of the metal
      ion (DeltaE = (3)pipi* - (5)D(0) = 6447 cm(-1)). Furthermore, in the present
      work, a mixed lanthanide system featuring Eu(3+) and Tb(3+) ions with the general
      formula {[Eu(0.5)Tb(0.5)(L)(3)(H(2)O)(2)]}(n) (4) was also synthesized, and the
      luminescent properties were evaluated and compared with those of the analogous
      single-lanthanide-ion systems (1 and 2). The lifetime measurements for 4 strongly
      support the premise that efficient energy transfer occurs between Tb(3+) and
      Eu(3+) in a mixed lanthanide system (eta = 86%).

PMID- 22862679
TI  - Expression of A1 adenosine receptors in the developing avian retina: in vivo
      modulation by A(2A)  receptors and endogenous adenosine.
AB  - Little is known about the mechanisms that regulate the expression of adenosine
      receptors during CNS development. We demonstrate here that retinas from chick
      embryos injected in ovo with selective adenosine receptor ligands show changes in
      A1 receptor expression after 48 h. Exposure to A1 agonist N6-cyclohexyladenosine
      (CHA) or antagonist 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX) reduced or
      increased, respectively, A1 receptor protein and [3H]DPCPX binding, but together,
      CHA+DPCPX had no effect. Interestingly, treatment with A(2A) agonist 3-[4-[2-[[6
      amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2
      yl]amino] ethyl]phenyl] propanoic acid (CGS21680) increased A1 receptor protein
      and [3H]DPCPX binding, and reduced A(2A) receptors. The A(2A) antagonists 7-(2
      phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-trizolo[1,5-c] pyrimidine
      (SCH58261) and 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazo-5-yl
      amino]ethyl)phenol (ZM241385) had opposite effects on A1 receptor expression.
      Exposure to CGS21680 + CHA did not change A1 receptor levels, whereas CHA +
      ZM241385 or CGS21680 + DPCPX had no synergic effect. The blockade of adenosine
      transporter with S-(4-nitrobenzyl)-6-thioinosine (NBMPR) also reduced [3H]DPCPX
      binding, an effect blocked by DPCPX, but not enhanced by ZM241385. [3H]DPCPX
      binding kinetics showed that treatment with CHA reduced and CGS21680 increased
      the Bmax, but did not affect Kd values. CHA, DPCPX, CGS21680, and ZM241385 had no
      effect on A1 receptor mRNA. These data demonstrated an in vivo regulation of A1
      receptor expression by endogenous adenosine or long-term treatment with A1 and
      A(2A) receptors modulators.

PMID- 22862680
TI  - Parenting and Child DRD4 Genotype Interact to Predict Children's Early Emerging
      Effortful Control.
AB  - Effortful control (EC), or the trait-like capacity to regulate dominant
      responses, has important implications for children's development. Although
      genetic factors and parenting likely influence EC, few studies have examined
      whether they interact to predict its development. This study examined whether the
      DRD4 exon III variable number tandem repeat polymorphism moderated the relation
      between parenting and children's EC. Three hundred and eighty-two 3-year-olds and
      primary caregivers completed behavioral tasks assessing children's EC and
      parenting. Children's DRD4 genotypes moderated the relation between parenting and
      EC: Children with at least one 7-repeat allele displayed lower EC in the context
      of negative parenting than children without this allele. These findings suggest
      opportunities for modifying early risk for low EC.

PMID- 22862681
TI  - Anion complexation and transport by isophthalamide and dipicolinamide
      derivatives: DNA plasmid transformation in E. coli.
AB  - Tris-arenes based on either isophthalic acid or 2,6-dipicolinic acid have been
      known for more than a decade to bind anions. Recent studies have also
      demonstrated their ability to transport various ions through membranes. In this
      report, we demonstrate two important properties of these simple diamides. First,
      they transport plasmid DNA into Escherichia coli about 2-fold over controls,
      where the ampicillin resistance gene is expressed in the bacteria. These studies
      were done with plasmid DNA (~2.6 kilobase (kb)) in JM109 E. coli cells. Second,
      known methods do not typically transport large plasmids (>15 kb). We demonstrate
      here that transformation of large pVIB plasmids (i.e., >20 kb) were enhanced over
      water controls by ~10-fold. These results are in striking contrast to the normal
      decrease in transformation with increasing plasmid size.

PMID- 22862682
TI  - Phenological mismatch strongly affects individual fitness but not population
      demography in a woodland passerine.
AB  - Populations are shifting their phenology in response to climate change, but these
      shifts are often asynchronous among interacting species. Resulting phenological
      mismatches can drive simultaneous changes in natural selection and population
      demography, but the links between these interacting processes are poorly
      understood. Here we analyse 37 years of data from an individual-based study of
      great tits (Parus major) in the Netherlands and use mixed-effects models to
      separate the within- and across-year effects of phenological mismatch between
      great tits and caterpillars (a key food source for developing nestlings) on
      components of fitness at the individual and population levels. Several components
      of individual fitness were affected by individual mismatch (i.e. late breeding
      relative to the caterpillar food peak date), including the probability of double
      brooding, fledgling success, offspring recruitment probability and the number of
      recruits. Together these effects contributed to an overall negative relationship
      between relative fitness and laying dates, that is, selection for earlier laying
      on average. Directional selection for earlier laying was stronger in years where
      birds bred on average later than the food peak, but was weak or absent in years
      where the phenology of birds and caterpillars matched (i.e. no population
      mismatch). The mean number of fledglings per female was lower in years when
      population mismatch was high, in part because fewer second broods were produced.
      Population mismatch had a weak effect on the mean number of recruits per female,
      and no effect on mean adult survival, after controlling for the effects of
      breeding density and the quality of the autumnal beech (Fagus sylvatica) crop.
      These findings illustrate how climate change-induced mismatch can have strong
      effects on the relative fitness of phenotypes within years, but weak effects on
      mean demographic rates across years. We discuss various general mechanisms that
      influence the extent of coupling between breeding phenology, selection and
      population dynamics in open populations subject to strong density regulation and
      stochasticity.

PMID- 22862683
TI  - Estimating overspray exposure potential from aerosol sprayed products onto
      surfaces.

PMID- 22862684
TI  - Compliance with anti-H1N1 vaccine among healthcare workers and general
      population.
AB  - Population protection through vaccination against infectious diseases has been
      one of the major achievements of public health care. The recent H1N1 influenza
      virus pandemic reopened the discussion on the strategic arrangements for
      vaccination in the face of spreading infection. Even though vaccination against a
      pandemic strain is considered to be one of the most effective countermeasures for
      protecting individuals, the general acceptance of H1N1 influenza vaccination has
      been low worldwide. The understanding of the potential health risks of the novel
      influenza A (H1N1) strain, the distrust of vaccinations and concerns about
      vaccine safety are the main reasons reported by the public for not undergoing
      vaccination. Concern about vaccine safety and distrust of health authorities are
      the commonest reasons given for low compliance with vaccination by healthcare
      workers. Better communication strategies to improve vaccination acceptance by the
      general population and by healthcare workers are required.

PMID- 22862685
TI  - Anesthetic considerations for rapid-onset obesity, hypoventilation, hypothalamic
      dysfunction, and autonomic dysfunction (ROHHAD) syndrome in children.
AB  - Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic
      dysfunction is an increasingly common diagnosis in patients who are being seen at
      tertiary care children's hospitals. We present two cases of anesthetics from the
      authors' own experience in addition to a comprehensive review of the disorder and
      anesthetic implications.

PMID- 22862686
TI  - Emerging treatment for chronic migraine and refractory chronic migraine.
AB  - INTRODUCTION: Chronic migraine (CM), the suffering of 15 or more headache days
      with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global
      population. CM is the most common disorder faced by experts in tertiary headache
      centers. When resistant to conventional medical treatment and prophylactic
      medication this condition is known as refractory chronic migraine (RCM). RCM is
      one of the greatest challenges in headache medicine. AREAS COVERED: State-of-the
      art and future medical treatments of chronic migraine include:
      OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate
      hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery
      systems of Sumatriptan, a well-established drug treatment for acute migraine),
      CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin
      receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other
      multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and
      BOL-148. The role for neuromodulation, the application of targeted electrical
      stimulation, will be examined. EXPERT OPINION: Medication overuse headache (MOH)
      is now recognized to be a major factor in many cases of both chronic and
      refractory chronic migraine. MOH must be addressed prior to evaluating the
      effectiveness of new preventative and prophylactic treatment approaches.
      Innovative new drugs and electrical neuromodulation are promising CM treatments.
      Future studies must carefully screen patients and acquire data that can lead to
      personalized, tailored treatment strategies.

PMID- 22862687
TI  - Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type
      plaques sparing the cerebellar cortex.
AB  - We describe an atypical neuropatholgical phenotype of sporadic Creutzfeldt-Jakob
      disease (sCJD) in a 64-year-old man presenting with a 5-month history of rapidly
      progressive dementia, comprising behavioral disturbances, memory complaints,
      disorientation and language alterations. MRI showed diffuse atrophy and
      hyperintensities in parietal, occipital, temporal and frontal cortices and left
      caudate nucleus on T2-weighted and fluid-attenuated inversion recovery images. No
      typical EEG alterations were observed. Repeated 14-3-3 assay was positive after a
      first negative test. Neuropathology showed classical CJD changes with small
      cortical foci of large confluent vacuoles and relatively well-preserved
      cerebellar cortex. The most striking feature was the presence of abundant Kuru
      type plaques in both cerebral cortex and subcortical white matter. Sparse Kuru
      type plaques were also seen in cerebellum, although only in white matter.
      Immunohistochemistry showed, in addition to unicentric plaques, diffuse synaptic
      and patchy perivacuolar, as well as plaque-like and periaxonal pathological prion
      protein deposits (PrP(res) ). Western blot studies demonstrated the co-occurrence
      of PrP(res) types 1 and 2 in frontal cortex and a relatively weak type 2 signal
      in cerebellum. PRNP genotyping revealed methionine homozygosity at codon 129 and
      excluded mutations. This case shows a previously undescribed combination of
      histopathological features which preclude its classification according to the
      current phenotypic and molecular sCJD classification. The observation
      demonstrates that Kuru-type amyloid plaques mainly involving the cerebral white
      matter may also occur in sCJD cases with short clinical course and the co
      existence of PrP(res) types 1 and 2. This case further highlights the complexity
      of the correlations between histopathological phenotype and PrP(res) isotype in
      prion diseases.

PMID- 22862688
TI  - Trade-offs between cattle production and bird conservation in an agricultural
      frontier of the Gran Chaco of Argentina.
AB  - Intensification of food production in tropical landscapes in the absence of land
      use planning can pose a major threat to biological diversity. Decisions on
      whether to spatially integrate or segregate lands for production and conservation
      depend in part on the functional relations between biological diversity and
      agricultural productivity. We measured diversity, density, and species
      composition of birds along a gradient of production intensification on an
      agricultural frontier of the Argentine Chaco, where dry tropical forests are
      cleared for cattle production. Bird species diversity in intact forests was
      higher than in any type of cattle-production system. Bird species richness
      decreased nonlinearly as cattle yield increased. Intermediate-intensity
      silvopastoral systems, those in which forest understory is selectively cleared to
      grow pastures of non-native plants beneath the tree canopy, produced 80% of the
      mean cattle yield obtained in pastures on cleared areas and were occupied by 70
      90% of the number of bird species present in the nearest forest fragments.
      Densities of >50% of bird species were significantly lower in open pastures than
      in silvopastoral systems. Therefore, intermediate-intensity silvopastoral systems
      may have the greatest potential to sustain cattle yield and conserve a large
      percentage of bird species. However, compared with low-intensity production
      systems, in which forest structure and extent were intact, intermediate-intensity
      silvopastoral systems supported significantly fewer forest-restricted bird
      species and fewer frugivorous birds. These data suggest that the integration of
      production and conservation through intermediate-intensity silvopastoral systems
      combined with the protection of forest fragments may be required to maintain
      cattle yield, bird diversity, and conservation of forest-restricted species in
      this agricultural frontier.

PMID- 22862689
TI  - Mitral anterolateral papillary muscle rupture in an asymptomatic patient with
      mitral stenosis after percutaneous mitral balloon valvuloplasty.

PMID- 22862690
TI  - Expression of human CYP27B1 in Escherichia coli and characterization in
      phospholipid vesicles.
AB  - CYP27B1 is a mitochondrial cytochrome P450 that catalyses the hydroxylation of 25
      hydroxyvitamin D3 at the C1alpha-position to give the hormonally active form of
      vitamin D3, 1alpha,25-dihydroxyvitamin D3. We successfully expressed human
      CYP27B1 in Escherichia coli and partially purified this labile enzyme and carried
      out a detailed characterization of its kinetic properties in a reconstituted
      membrane environment. The phospholipid concentration did not affect the enzyme
      activity in the vesicle-reconstituted system, although it was influenced by the
      phospholipid composition, with the addition of cardiolipin lowering the K(m)  for
      25-hydroxyvitamin D3. These data are consistent with the enzyme accessing
      substrate from the hydrophobic domain of the vesicle membrane. Cardiolipin also
      caused the appearance of inhibition of activity at high substrate concentrations.
      This substrate inhibition fitted a model for one catalytic and two inhibitory
      sites on the enzyme for the binding of substrate. The K(m)  for human adrenodoxin
      was observed to decrease with decreasing substrate concentration, with the
      catalytic efficiency (k(cat) /K(m) ) being largely independent of adrenodoxin
      concentration. Human CYP27B1 was also active on 25-hydroxyvitamin D(2)  and on
      intermediates of the CYP24A1-mediated inactivation pathway, 24R,25
      dihydroxyvitamin D3, 24-oxo-25-hydroxyvitamin D3 and 24-oxo-23,25
      dihydroxyvitamin D3, with all these substrates showing comparable k(cat)  values
      of 50-71 min(-1) , similar to 25-hydroxyvitamin D3. The latter two substrates
      gave higher K(m)  values than that for 25-hydroxy-vitamin D3. The present study
      shows that human CYP27B1 can be partially purified in an active form with the
      enzyme displaying high activity towards a range of substrates in a phospholipid
      vesicle-reconstituted system that mimics the inner-mitochondrial membrane.

PMID- 22862733
TI  - Murine spleen contains a diversity of myeloid and dendritic cells distinct in
      antigen presenting function.
AB  - The spleen contains multiple subsets of myeloid and dendritic cells (DC). DC are
      important antigen presenting cells (APC) which induce and control the adaptive
      immune response. They are cells specialized for antigen capture, processing and
      presentation to naive T cells. However, DC are a heterogeneous population and
      each subset differs subtly in phenotype, function and location. Similarly,
      myeloid cell subsets can be distinguished which can also play an important role
      in the regulation of immunity. This review aims to characterize splenic subsets
      of DC and myeloid cells to better understand their individual roles in the immune
      response.

PMID- 22862734
TI  - Astrocyte-specific expression of survivin after intracerebral hemorrhage in mice:
      a possible role in reactive gliosis?
AB  - Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke,
      accounts for up to 15% of all strokes. Despite maximal surgical intervention and
      supportive care, ICH is associated with significant morbidity and mortality, in
      part due to a lack of viable treatment options. Astrogliosis, a key feature of
      secondary injury that is characterized by glial proliferation, is a poorly
      defined process that may produce both beneficial and detrimental outcomes after
      brain injury. Using a pre-clinical murine model of collagenase-induced ICH, we
      demonstrate a delayed upregulation of survivin, a key molecule involved in tumor
      cell proliferation and survival, by 72 h post-ICH. Notably, this increase in
      survivin expression was prominent in GFAP-positive astrocytes, but absent in
      neurons. Survivin was not expressed at detectable levels in the striatum of sham
      operated mice. The expression of survivin after ICH was temporally and spatially
      associated with the expression of proliferating cell nuclear antigen (PCNA), an
      established marker of cellular proliferation. Moreover, the survivin expression
      was co-localized in proliferating astrocytes as evidenced by triple-label
      immunohistochemistry. Finally, shRNA-mediated silencing of survivin expression
      attenuated PCNA expression and reduced cellular proliferation in human glial
      cells. Together, these data suggest a potentially novel role for survivin in
      functionally promoting astrocytic proliferation after ICH.

PMID- 22862735
TI  - Association between glycemic control and hip fracture.
AB  - OBJECTIVES: To determine whether tight glycemic control is associated with
      greater risk of hip fractures in individuals being treated for type 2 diabetes
      mellitus. DESIGN: Case-control study. SETTING: Tertiary hospital. PARTICIPANTS:
      Cases were selected from all individuals with diabetes mellitus admitted between
      2005 and 2010 to Changi General Hospital for hip fracture (N = 932). Cases were
      included if their glycosylated hemoglobin (HbA1c) had been measured within 3
      months of the fracture and they were undergoing treatment with oral hypoglycemic
      medications or insulin. Each case was matched with one control for sex, age,
      race, duration of diabetes mellitus, and comorbidities. MEASUREMENTS: Information
      on baseline characteristics, HbA1c, and use of diabetic medications was obtained.
      The likelihood of hip fracture was determined comparing four different values of
      HbA1c [<6%, 6.1-7.0%, 7.1-8.0%, >8% (reference group)] and use of diabetic
      medications. RESULTS: The mean age of cases was 77.3 +/- 7.7, and 73.3% were
      female. After adjusting for age, sex, race, comorbidities, and other covariates,
      participants with tighter glycemic control (HbA1c < 6% and 6.1-7.0%) were more
      likely to have a hip fracture than those with HbA1c >8% (odds ratio (OR) = 3.01,
      95% confidence interval (CI) = 2.01-4.51, P < .001; and OR = 2.34, 95% CI=1.71
      3.22, P < .001, respectively). The use of insulin and sulfonylurea was similar
      between cases and controls. CONCLUSION: The present study found an association
      between tight glycemic control (when HbA1c < 7%) and greater risk of hip fracture
      in individuals being treated for type 2 diabetes mellitus. Greater caution needs
      to be exercised in treating older patients with diabetes mellitus.

PMID- 22862736
TI  - Influenza A H1N1 induces declines in alveolar gas exchange in mice consistent
      with rapid post-infection progression from acute lung injury to ARDS.
AB  - BACKGROUND: Patients with severe seasonal or pandemic influenza pneumonia
      frequently develop acute respiratory distress syndrome (ARDS). One clinical
      diagnostic criterion for ARDS is the P(a)O(2):F(i)O(2) ratio, which is an index
      of alveolar gas exchange. However, effects of H1N1 influenza infection on
      P(a)O(2):F(i)O(2) ratios and related pathophysiologic readouts of lung function
      have not been reported in mice. METHODS: To develop a method for determining
      P(a)O(2):F(i)O(2) ratios, uninfected mice were anesthetized with pentobarbital,
      diazepam/ketamine, or inhaled isoflurane. Subsequently, they were allowed to
      breathe spontaneously or were mechanically ventilated. After 15 minutes exposure
      to room air (F(i)O(2) = 0.21) or 100% O(2) (F(i)O(2) = 1.0), carotid P(a)O(2) was
      measured. To determine influenza effects on P(a)O(2):F(i)O(2), mice were
      challenged with 10,000 p.f..u./mouse influenza A/WSN/33. RESULTS:
      P(a)O(2):F(i)O(2) ratios were abnormally low (<=400 mmHg) in spontaneously
      breathing mice. Mechanical ventilation with positive end-expiratory pressure was
      required to obtain P(a)O(2):F(i)O(2) ratios in uninfected mice consistent with
      normal values in humans (>=600 mmHg). At day 2 following infection
      P(a)O(2):F(i)O(2) ratios indicated the onset of acute lung injury. By day 6,
      P(a)O(2):F(i)O(2) ratios were <200 mmHg, indicating progression to ARDS. Impaired
      gas exchange in influenza-infected mice was accompanied by progressive hemoglobin
      desaturation, hypercapnia, uncompensated respiratory acidosis, hyperkalemia, and
      polycythemia. CONCLUSIONS: Influenza infection of mice results in impairment of
      alveolar gas exchange consistent with rapid development of acute lung injury and
      progression to ARDS. P(a)O(2):F(i)O(2) ratios may be of utility as clinically
      relevant and predictive outcome measures in influenza pathogenesis and treatment
      studies that use mouse models.

PMID- 22862737
TI  - Food patterns and dietary quality associated with organic food consumption during
      pregnancy; data from a large cohort of pregnant women in Norway.
AB  - BACKGROUND: Little is known about the consumption of organic food during
      pregnancy. The aim of this study was to describe dietary characteristics
      associated with frequent consumption of organic food among pregnant women
      participating in the Norwegian Mother and Child Cohort Study (MoBa). METHODS: The
      present study includes 63 808 women who during the years 2002-2007 answered two
      questionnaires, a general health questionnaire at gestational weeks 15 and a food
      frequency questionnaire at weeks 17-22. The exploration of food patterns by
      Principal component analyses (PCA) was followed by ANOVA analyses investigating
      how these food patterns as well as intake of selected food groups were associated
      with consumption of organic food. RESULTS: The first principal component (PC1)
      identified by PCA, accounting for 12% of the variation, was interpreted as a
      'health and sustainability component', with high positive loadings for
      vegetables, fruit and berries, cooking oil, whole grain bread and cereal products
      and negative loadings for meat, including processed meat, white bread, and cakes
      and sweets. Frequent consumption of organic food, which was reported among 9.1%
      of participants (n = 5786), was associated with increased scores on the 'health
      and sustainability component' (p < 0.001). The increase in score represented
      approximately 1/10 of the total variation and was independent of sociodemographic
      and lifestyle characteristics. Participants with frequent consumption of organic
      food had a diet with higher density of fiber and most nutrients such as folate,
      beta-carotene and vitamin C, and lower density of sodium compared to participants
      with no or low organic consumption. CONCLUSION: The present study showed that
      pregnant Norwegian women reporting frequent consumption of organically produced
      food had dietary pattern and quality more in line with public advice for healthy
      and sustainable diets. A methodological implication is that the overall diet
      needs to be included in future studies of potential health outcomes related to
      consumption of organic food during pregnancy.

PMID- 22862738
TI  - Cardiac venous left ventricular lead removal and reimplantation following device
      infection: a large single-center experience.
AB  - BACKGROUND: Early series of biventricular device removal have contained mostly
      younger cardiac venous (CV) left ventricular leads and few have reported on rates
      of successful reimplantation. METHODS AND RESULTS: We performed a retrospective
      analysis of all patients referred to the Cleveland Clinic between February 2,
      2001 and July 27, 2011 for removal of a biventricular device with a CV pacing
      lead for an infectious indication. A total of 173 patients were included. The
      median age of the CV leads was 22.3 months (interquartile range: 5.2-46.3
      months). The complete procedural success rate for all leads was 97.7%, with the
      remaining 2.3% clinical successes. A total of 76.9% of CV leads were removed
      using simple traction alone with the remaining leads requiring the use of a laser
      powered sheath. A total of 3.5% of leads required intervention (manual dissection
      or laser-powered dissection) within the coronary sinus (CS). Major complications
      occurred in 1.2% of patients. Minor complications occurred in 7.5% of patients,
      the majority of which were hematomas requiring drainage (6.9%). CV lead
      reimplantation was attempted in 107 patients of which 88 (82.8%) were successful.
      CONCLUSION: CV lead removal in patients with an infected biventricular device is
      associated with an extremely high procedural success rate and a low incidence of
      major complications. The use of a laser-powered sheath is necessary in roughly
      one-quarter of cases with a very small percentage requiring intervention within
      the CS. Reimplantation of CV leads is achievable in roughly 83% of patients, a
      figure lower than nationally quoted estimates for de novo implantations.

PMID- 22862739
TI  - High non-specific T lymphocyte response to the adjuvanted H1N1 vaccine in
      comparison with the H1N1/H3N2/B-Brisbane vaccine without adjuvant.
AB  - Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine
      manufacturers, in conjunction with public agencies, started developing a H1N1
      vaccine. In 2009, various approaches were implemented around the globe. The
      United States and Australia finally approved only non-adjuvanted H1N1 influenza
      vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010,
      seasonal influenza vaccine without adjuvant was again widely accepted in both
      hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of
      the vaccine in the presence of a relatively low amount of antigen. However, it
      might also induce undesirable non-specific immune response. For this reason, we
      conducted a prospective observational study to monitor T cell absolute count and
      H1N1-specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy
      volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5
      MUg of H1N1 and squalene-based adjuvant) in October 2009. The immunization was
      associated with a significant increase in T lymphocyte absolute count (P <
      0.0001), reaching abnormal values in 57% of subjects. During this period, none of
      the subject showed any manifestation of severe viral infection or inflammation.
      Acute infection by CMV or EBV viruses was also excluded. In October 2010, the
      same subjects received a seasonal non-adjuvanted influenza vaccine (15 MUg of
      each: H1N1, H3N2, and B-Brisbane). However, after 2010 immunization, no change in
      T lymphocyte absolute count was observed. H1N1-induced immunogenicity was good
      for both vaccines. Our results suggest a pronounced non-specific T cell response
      after AS03-adjuvanted 2009 H1N1 vaccination.

PMID- 22862740
TI  - Substrate-assisted self-organization of radial beta-AgVO3 nanowire clusters for
      high rate rechargeable lithium batteries.
AB  - Rational assembly of unique complex nanostructures is one of the facile
      techniques to improve the electrochemical performance of electrode materials.
      Here, a substrate-assisted hydrothermal method was designed and applied in
      synthesizing moundlily like radial beta-AgVO(3) nanowire clusters. Gravitation
      and F(-) ions have been demonstrated to play important roles in the growth of
      beta-AgVO(3) nanowires (NWs) on substrates. The results of cyclic voltammetry
      (CV) measurement and X-ray diffraction (XRD) characterization proved the phase
      transformation from beta-AgVO(3) to Ag(1.92)V(4)O(11) during the redox reaction.
      Further electrochemical investigation showed that the moundlily like beta-AgVO(3)
      nanowire cathode has a high discharge capacity and excellent cycling performance,
      mainly due to the reduced self-aggregation. The capacity fading per cycle from
      3rd to 51st is 0.17% under the current density of 500 mA/g, which is much better
      than 1.46% under that of 20 mA/g. This phenomenon may be related to the Li(+)
      diffusion and related kinetics of the electrode. This method is shown to be an
      effective and facile technique for improving the electrochemical performance for
      applications in rechargeable Li batteries or Li ion batteries.

PMID- 22862741
TI  - Development and assessment of sensitive immuno-PCR assays for the quantification
      of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies.
AB  - Characteristic tau isoform composition of the insoluble fibrillar tau inclusions
      define tauopathies, including Alzheimer's disease (AD), progressive supranuclear
      palsy (PSP) and frontotemporal dementia with parkinsonism linked to chromosome
      17/frontotemporal lobar degeneration-tau (FTDP-17/FTLD-tau). Exon 10 splicing
      mutations in the tau gene, MAPT, in familial FTDP-17 cause elevation of tau
      isoforms with four microtubule-binding repeat domains (4R-tau) compared to those
      with three repeats (3R-tau). On the basis of two well-characterised monoclonal
      antibodies against 3R- and 4R-tau, we developed novel, sensitive immuno-PCR
      assays for measuring the trace amounts of these isoforms in CSF. This was with
      the aim of assessing if CSF tau isoform changes reflect the pathological changes
      in tau isoform homeostasis in the degenerative brain and if these would be
      relevant for differential clinical diagnosis. Initial analysis of clinical CSF
      samples of PSP (n = 46), corticobasal syndrome (CBS; n = 22), AD (n = 11),
      Parkinson's disease with dementia (PDD; n = 16) and 35 controls revealed
      selective decreases of immunoreactive 4R-tau in CSF of PSP and AD patients
      compared with controls, and lower 4R-tau levels in AD compared with PDD. These
      decreases could be related to the disease-specific conformational masking of the
      RD4-binding epitope because of abnormal folding and/or aggregation of the 4R-tau
      isoforms in tauopathies or increased sequestration of the 4R-tau isoforms in
      brain tau pathology.

PMID- 22862742
TI  - Influence of a static magnetic field on the slow freezing of human erythrocytes.
AB  - PURPOSE: The aim of this study was to test whether or not a strong static
      magnetic field (SMF) had a positive effect on the survival rate of frozen
      erythrocytes. MATERIALS AND METHODS: Human erythrocytes were slow freezing at a
      rate of -1 degrees C/min, to a final temperature of -20 degrees C. During the
      freezing process, the cells were simultaneously exposed to an SMF with a magnetic
      induction of 0.2 or 0.4 T. After the cells were thawed, the survival rate,
      morphology, and function of the thawed erythrocytes were evaluated. Furthermore,
      tests of membrane fluidity were performed to assess the effect of the SMF on the
      cell membrane. RESULTS: The slow freezing process coupled with an SMF increased
      the survival rate of frozen erythrocytes, without any negative effect on the cell
      morphology or function. The increases in relative survival rates of frozen
      erythrocytes were 5.7% and 9.1% when the cells were frozen in 0.2 T and 0.4 T
      groups, respectively. In addition, the 0.4 T group significantly increased the
      membrane rigidity of the erythrocytes. CONCLUSIONS: Slow freezing coupled with a
      strong SMF produced positive effects on the survival rate of thawed erythrocytes,
      without changing their normal function.

PMID- 22862744
TI  - Preventing influenza in younger children.
AB  - Influenza is common in infants and children: attack rates vary from 23% to 48%
      each year during inter-pandemic periods, and are even higher during pandemics.
      Severe cases occur more frequently in children with underlying chronic diseases;
      however, epidemiological studies have clearly shown that influenza also causes an
      excess of medical examinations, drug prescriptions and hospitalizations in
      otherwise healthy children (particularly those aged <5 years), as well as a
      considerable number of paediatric deaths. Childhood influenza also has a number
      of social and economic consequences. However, many European health authorities
      are still reluctant to include influenza vaccinations in their national
      vaccination programmes for healthy children because, among other things, there
      are doubts concerning their real ability to evoke a protective immune response,
      especially in children in the first years of life. New hope for the solution of
      these problems has come from the introduction of vaccines containing more
      antigens and the possibility of intradermal administration. However, further
      studies are needed to establish whether universal influenza vaccination in the
      first years of life should be recommended, and with which vaccine.

PMID- 22862743
TI  - High throughput sequencing reveals novel and abiotic stress-regulated microRNAs
      in the inflorescences of rice.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that play important
      regulatory roles in plant development and stress responses. Identification of
      stress-regulated miRNAs is crucial for understanding how plants respond to
      environmental stimuli. Abiotic stresses are one of the major factors that limit
      crop growth and yield. Whereas abiotic stress-regulated miRNAs have been
      identified in vegetative tissues in several plants, they are not well studied in
      reproductive tissues such as inflorescences. RESULTS: We used Illumina deep
      sequencing technology to sequence four small RNA libraries that were constructed
      from the inflorescences of rice plants that were grown under control condition
      and drought, cold, or salt stress. We identified 227 miRNAs that belong to 127
      families, including 70 miRNAs that are not present in the miRBase. We validated
      62 miRNAs (including 10 novel miRNAs) using published small RNA expression data
      in DCL1, DCL3, and RDR2 RNAi lines and confirmed 210 targets from 86 miRNAs using
      published degradome data. By comparing the expression levels of miRNAs, we
      identified 18, 15, and 10 miRNAs that were regulated by drought, cold and salt
      stress conditions, respectively. In addition, we identified 80 candidate miRNAs
      that originated from transposable elements or repeats, especially miniature
      inverted-repeat elements (MITEs). CONCLUSION: We discovered novel miRNAs and
      stress-regulated miRNAs that may play critical roles in stress response in rice
      inflorescences. Transposable elements or repeats, especially MITEs, are rich
      sources for miRNA origination.

PMID- 22862745
TI  - Interactions of pathogen-containing compartments with the secretory pathway.
AB  - A subgroup of intracellular pathogens reside and replicate within membrane-bound
      compartments often termed pathogen-containing compartments (PCC). PCCs navigate
      around a wide range of host cell vesicles and organelles. In light of the perils
      of engaging with vesicles of the endocytic pathway, most PCCs modulate their
      interactions with endocytic vesicles while a few avoid those interactions. The
      secretory pathway constitutes another important grouping of vesicles and
      organelles in host cells. Although the negative consequences of engaging with the
      secretory pathway are not known, there is evidence that PCCs interact
      differentially with vesicles and organelles in this pathway as well. In this
      review, we consider three prokaryote pathogens and two protozoan parasites for
      which there is information on the interactions of their PCCs with the secretory
      pathway. Current understandings of the molecular interactions as well as the
      metabolic benefits that accompany those interactions are discussed. Not
      unexpectedly, our understanding of the extent of these interactions is variable.
      An underlying theme that is brought to the fore is that PCCs establish
      preferential interactions with distinct compartments of the secretory pathway.

PMID- 22862746
TI  - Health among Swedish employees and financial situation, education, and managerial
      responsibility: a longitudinal study.
AB  - BACKGROUND: The present study is part of a 3-year longitudinal study on work and
      health among employees in the public sector in Sweden. The aim was to study
      associations between self-rated health (SRH) and financial situation, education,
      and managerial responsibility. METHODS: Of the 9003 employees, 7533 answered the
      baseline questionnaires (84%). Altogether 9373 subjects received the follow-up
      questionnaire, and 6617 subjects responded (71%). In total 4240 completed the
      questionnaire on both occasions, and this group comprised the study population.
      SRH consisted of the response to a single question: 'In general, would you say
      your health is excellent, very good, good, poor, or very poor?' The health was
      investigated in terms of the development of health status in the 3-year follow
      up. The exposure factors were: financial situation, education, and managerial
      responsibility. Odds ratios were analysed using logistic regressions. RESULTS:
      Good financial situation and further education were predictors in maintaining
      good health and in avoiding poor health. The analysis also indicated the
      following determinants of sustained good SRH: having a good financial situation
      (OR 1.99 at baseline and OR 1.87 at follow-up), having a further education
      compared to lower education (OR 1.17 at baseline), and not having a worsening
      financial situation between baseline and follow-up (OR 0.53). CONCLUSION:
      Financial situation and educational level were important factors that influence
      the subjective perception of health.

PMID- 22862747
TI  - HIV serostatus and tumor differentiation among patients with cervical cancer at
      Bugando Medical Centre.
AB  - BACKGROUND: Evidence for the association between Human immunodeficiency virus
      infection and cervical cancer has been contrasting, with some studies reporting
      increased risk of cervical cancer among HIV positive women while others report no
      association. Similar evidence from Tanzania is scarce as HIV seroprevalence among
      cervical cancer patients has not been rigorously evaluated. The purpose of this
      study was to determine the association between HIV and tumor differentiation
      among patients with cervical cancer at Bugando Medical Centre and Teaching
      Hospital in Mwanza, North-Western Tanzania. METHODS: This was a descriptive
      analytical study involving suspected cervical cancer patients seen at the
      gynaecology outpatient clinic and in the gynaecological ward from November 2010
      to March 2011. RESULTS: A total of 91 suspected cervical cancer patients were
      seen during the study period and 74 patients were histologically confirmed with
      cervical cancer. The mean age of those confirmed of cervical cancer was 50.5 +/-
      12.5 years. Most patients (39 of the total 74-52.7%) were in early disease stages
      (stages IA-IIA). HIV infection was diagnosed in 22 (29.7%) patients. On average,
      HIV positive women with early cervical cancer disease had significantly more CD4+
      cells than those with advanced disease (385.8 +/- 170.4 95% CI 354.8-516.7 and
      266.2 +/- 87.5, 95% CI 213.3-319.0 respectively p = 0.042). In a binary logistic
      regression model, factors associated with HIV seropositivity were ever use of
      hormonal contraception (OR 5.79 95% CI 1.99-16.83 p = 0.001), aged over 50 years
      (OR 0.09 95% CI 0.02-0.36 p = 0.001), previous history of STI (OR 3.43 95% CI
      1.10-10.80 p = 0.035) and multiple sexual partners OR 5.56 95% CI 1.18-26.25 p =
      0.030). Of these factors, only ever use of hormonal contraception was associated
      with tumor cell differentiation (OR 0.16 95% CI 0.06-0.49 p = 0.001). HIV
      seropositivity was weakly associated with tumor cell differentiation in an
      unadjusted analysis (OR 0.21 95% CI 0.04-1.02 p = 0.053), but strong evidence for
      the association was found after adjusting for ever use of hormonal contraception
      with approximately six times more likelihood of HIV infection among women with
      poorly differentiated tumor cells compared to those with moderately and well
      differentiated cells (OR 5.62 95% CI 1.76-17.94 p = 0.004). CONCLUSION: Results
      from this study setting suggest that HIV is common among cervical cancer patients
      and that HIV seropositivity may be associated with poor tumour differentiation.
      Larger studies in this and similar settings with high HIV prevalence and high
      burden of cervical cancer are required to document this relationship.

PMID- 22862748
TI  - Primary epidural lymphocyte-depleted Hodgkin's lymphoma of the thoracic spine -
      presentation of a rare disease variant.
AB  - BACKGROUND: Lymphocyte-depleted Hodgkin's lymphoma is the rarest form of
      classical Hodgkin's lymphoma, accounting for < 1% of all cases. Patients often
      have advanced-stage disease at the time of presentation with an aggressive
      clinical course. Even more uncommon is primary extranodal disease and rarely it
      will be presenting with spinal cord compression. CASE PRESENTATION: An 88-year
      old Caucasian female presented with a history of upper back pain for several
      months and new onset bilateral leg numbness and weakness. MRI of the spine showed
      a dorsal epidural lesion with cord compression at T1-T4 with involvement of the
      paraspinal muscles. The patient received urgent surgical decompression, with
      final histopathology showing a lymphocyte-depleted Hodgkin's lymphoma. Systemic
      work-up did not show evidence of nodal disease. Following surgery, she received a
      course of radiotherapy with good outcome. CONCLUSION: To the best of our
      knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin
      lymphoma presenting as epidural spinal cord compression. Our report, in
      conjunction with a review of the literature, suggests that surgical intervention
      is clearly indicated in de novo disease followed by radiotherapy.

PMID- 22862749
TI  - Can infants be protected by means of maternal vaccination?
AB  - The administration of vaccines is not usually recommended in pregnant women
      because of a fear of severe adverse events for the fetus. However,
      contraindication to vaccination applies only to vaccines based on live attenuated
      viruses for the theoretical possibility that they might infect the fetus. In
      contrast, the use of several inactivated vaccines is useful and recommended. As a
      result of the transplacental passage of antibodies, maternal immunization can
      reduce the risk of vaccine-preventable diseases that may occur in the first
      months of life before the start or completion of the suggested vaccination
      schedule. One of the best examples is vaccination against influenza that can
      protect pregnant women from a disease that can lead to hospitalization and death
      in a significantly higher number of cases than in the general population and can
      induce protective specific antibody levels as well as being effective in infants
      in the first months of life. Other examples are vaccinations against tetanus,
      pertussis, pneumococcal infections and Haemophilus influenzae type b infection.
      This review analyses the advantages and limitations of maternal immunization as
      revealed by experience and the main publications.

PMID- 22862750
TI  - What do emergency physicians think of law?

PMID- 22862751
TI  - Review article: A primer for clinical researchers in the emergency department:
      Part III: How to write a scientific paper.
AB  - In this series we address key topics for clinicians who conduct research as part
      of their work in the ED. Analysis of research data does not represent the
      completion of a project as the findings need to be communicated to clinicians and
      other researchers in the field. In this section, we describe how to write up
      clinical research data for publication in a peer-reviewed journal. We also
      describe the editorial and peer-review process.

PMID- 22862752
TI  - Prospective comparison of point-of-care international normalised ratio
      measurement versus plasma international normalised ratio for acute traumatic
      coagulopathy.
AB  - OBJECTIVE: Early detection of acute traumatic coagulopathy (ATC) might be useful
      to guide trauma resuscitation. This study aimed to compare results from a point
      of-care (POC) international normalised ratio (INR) measuring device with plasma
      INR in acute trauma patients. METHODS: This was a single-centre, prospective,
      blinded comparative study. All trauma patients meeting trauma call-out criteria
      in a major trauma centre were screened. Patients predicted to have ATC were
      identified by the Coagulopathy of Severe Trauma score and a convenience sample of
      72 patients included in this study. Whole blood was used to measure INR at the
      bedside, whereas blood from the same sample was sent to the hospital laboratory
      for plasma INR testing. Agreement between the laboratory and bedside INR was
      determined using a Bland-Altman plot. RESULTS: There were 38 (52.8%) patients
      with ATC by laboratory measure, defined as INR >1.5 or activated partial thrombin
      time >60 s, whereas the POC system identified 28 (38.9%) patients with an INR
      >1.5. Assuming the laboratory measure as the gold standard, the POC system had a
      specificity of 88.2% (95% confidence interval 71.6-96.2) and a sensitivity of
      63.1% (95% confidence interval 46.0-77.7). Bland-Altman plots demonstrated
      inadequate agreement between the two methods of INR measurement for the major
      trauma patient. CONCLUSIONS: POC INR measurements using this method during the
      trauma reception and resuscitative phases cannot be used to identify or exclude
      patients with ATC. Further studies are required to determine if there is any role
      for POC INR measures during trauma resuscitation.

PMID- 22862753
TI  - Use of step stool during resuscitation improved the quality of chest compression
      in simulated resuscitation.
AB  - OBJECTIVES: Resuscitation on a medical bed is difficult because of the need to
      match the height of the bed to the height of the rescuer, which is impossible on
      a fixed-height medical bed. This study investigated the effect of using a step
      stool on chest compressions performed on a manikin in a fixed-height medical bed.
      METHODS: This prospective, observational study was performed using simulated
      resuscitation manikins and a fixed-height (78 cm) medical bed. Chest compression
      ventilation of more than five cycles was performed with and without a 20-cm-high
      step stool. A total of 74 medical students participated in this study. The
      quality of the chest compressions was examined using the Laerdal PC Skill
      Reporting System. The angle between the arm of the rescuer and the bed was
      measured. In addition, whether the heels of the rescuer reached the ground during
      the compressions was assessed using lateral-view pictures. RESULTS: Use of the
      step stool improved the quality of the chest compressions with regard to depth,
      proper compressions, insufficient compressions and incorrect hand position (P <
      0.05). The angle between the rescuer's arm and bed during the chest compressions
      was closer to vertical with the use of the step stool than without it (average
      angle, 83.84 +/- 4.16 degrees  and 73.41 +/- 9.16 degrees , respectively; P <
      0.001). CONCLUSIONS: In-hospital resuscitation was conducted on a fixed-height
      medical bed by rescuers of different heights. The use of a step stool may improve
      the quality and effectiveness of chest compressions, particularly for short
      rescuers.

PMID- 22862754
TI  - Senior Streaming Assessment Further Evaluation after Triage zone: a novel model
      of care encompassing various emergency department throughput measures.
AB  - OBJECTIVE: Access block (AB) and hospital overcrowding adversely affect ED
      functionality. ED throughput measures have been described in the literature with
      positive impacts on key performance indicators (KPIs)--time to first seen, did
      not-wait rates, off-stretcher times for ambulances and ED length of stay figures.
      In this study, we aimed to assess the impact of a new model of care, the Senior
      Streaming Assessment Further Evaluation after Triage (SAFE-T) zone concept on ED
      performance indicators and statistical outcomes. METHODS: We implemented a model
      of care at our tertiary hospital ED amalgamating multiple ED throughput
      interventions. These interventions included dynamic transition waiting room
      concept, early senior ED physician assessment and decision-making, early
      streaming, acute-care bed quarantining and ED short stay and observation units.
      The principal intervention was the SAFE-T zone. End-point data were compared for
      similar periods (77 days) of 2010 and 2011 with and without the new model of
      care. RESULTS: In total, 11 408 and 11 845 patients were included in the study
      periods pre- and post-intervention, respectively. Time to physician KPI improved
      from 72.5% to 84.1%. Did-not-wait rates dropped from 10.7% to 9.6% (P= 0.02) and
      off-stretcher times for ambulances KPI improved from 74.5% to 79.5% (P < 0.001).
      ED length of stay dropped most significantly for Australasian Triage Scale
      categories 3 and 4 (14.3% and 11.8%, P-values <0.001). These results were
      achieved despite worsened AB and hospital bed-occupancy rates during the
      intervention period (+3.9% and +6.7%). CONCLUSIONS: The SAFE-T zone model of care
      involving multiple ED throughput measures achieved improvements in ED performance
      despite AB and hospital overcrowding.

PMID- 22862755
TI  - Once or twice-daily, algorithm-based intravenous cephazolin for home-based
      cellulitis treatment.
AB  - OBJECTIVE: Cellulitis is a common presentation to the ED and a significant cause
      of hospitalization that can be managed in hospital-in-the-home programmes.
      Current clinical-practice guidelines recommend once or twice-daily i.v.
      antibiotics; however, there is an absence of data describing the impact of these
      guidelines in real-world practice-based settings. This study aims to describe the
      safety and effectiveness of home-based cellulitis treatment according to an
      online treatment algorithm. METHODS: Over 12 months, 301 patients with a
      diagnosis of uncomplicated cellulitis requiring i.v. antibiotics and eligible for
      home-based therapy completed once-daily (cephazolin plus probenecid) or twice
      daily (cephazolin alone) treatment, according to the treatment algorithm. Time
      (days) until non-progression of cellulitis was the primary outcome measure.
      Length of stay and treatment-related side-effects were also recorded. RESULTS:
      The mean time until non-progression was 2.11 (95% confidence interval [CI] 1.98
      2.23) days versus 2.13 (95% CI 1.81-2.45) days for the once-daily (n = 213) and
      twice-daily (n = 88) regimens, respectively (P = 0.92, difference in means 0.02
      [95% CI -0.36-0.33]). The corresponding mean length of stay was 6.55 (95% CI 5.96
      7.15) days versus 7.67 (95% CI 6.69-8.65) days (P = 0.06, difference in means
      1.12 [CI 0.03-1.23]). Treatment-related side-effects were reported in 15.5%
      (33/213 [95% CI 10.6-20.3]) of patients receiving the once-daily regimen compared
      with 9.1% (8/88 [95% CI 3.1-15.1]) treated twice-daily. Application of the once
      daily strategy increased hospital-in-the-home cellulitis-related treatment
      capacity by 52% (1396/2688 [95% CI 50-54]). CONCLUSIONS: An online decision
      support algorithm can support the effective use of a once or twice-daily
      treatment regimen for uncomplicated cellulitis. This approach can increase the
      efficiency and capacity of home-based therapy, resulting in better alignment of
      treatment options with clinicians and patients' preferences.

PMID- 22862756
TI  - Impact of a government triple zero awareness campaign on emergency department
      patient characteristics.
AB  - OBJECTIVE: To evaluate the impact of a government triple zero community awareness
      campaign on the characteristics of patients attending an ED. METHODS: A study
      using Emergency Department Information System data was conducted in an adult
      metropolitan tertiary-referral teaching hospital in Brisbane. The three outcomes
      measured in the 3 month post-campaign period were arrival mode, Australasian
      Triage Scale and departure status. These measures reflect ambulance usage,
      clinical urgency and illness severity, respectively. They were compared with
      those in the 3 month pre-campaign period. Multivariate logistic regression models
      were used to investigate the impacts of the campaign on each of the three outcome
      measures after controlling for age, sex, day and time of arrival, and daily
      minimum temperature. RESULTS: There were 17,920 visits in the pre- and 17,793
      visits in the post-campaign period. After the campaign, fewer patients arrived at
      the ED by road ambulance (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.80
      1.00), although the impact of the campaign on the arrival mode was only close to
      statistical significance (Wald chi(2) -test, P= 0.055); and patients were
      significantly less likely to have higher clinical urgency (OR 0.86, 95% CI 0.79
      0.94), while more likely to be admitted (OR 1.68, 95% CI 1.38-2.05) or complete
      treatment in the ED (OR 1.46, 95% CI 1.23-1.73) instead of leaving without
      waiting to be seen. CONCLUSIONS: The campaign had no significant impact on the
      arrival mode of the patients. After the campaign, the illness acuity of the
      patients decreased, whereas the illness severity of the patients increased.

PMID- 22862757
TI  - Performance of the New South Wales Ambulance Service major trauma transport
      protocol (T1) at an inner city trauma centre.
AB  - OBJECTIVE: To evaluate the performance of a newly implemented prehospital trauma
      triage (T1) protocol in New South Wales for patients transported to an inner city
      major trauma centre. METHODS: An observational study was conducted over 1 year.
      Prehospital data and injury characteristics were collected prospectively for all
      hospital trauma team activations and injury presentations transported by
      Ambulance Service of New South Wales. Univariate comparison of T1- and non-T1
      transported patients was performed and sensitivity, specificity, overtriage and
      undertriage rates were calculated. The outcomes studied were Injury Severity
      Score >15 and major outcome (composite of in-hospital death and/or transferred
      from the ED to operating theatre or intensive care unit). Factors associated with
      undertriage were determined with univariate analysis. RESULTS: A total of 2664
      ambulance arrivals for trauma were studied with 767(29%) transported on the T1
      protocol. T1-transported patients were associated with more severe injury (23% vs
      6%, P < 0.001) and major outcomes (30% vs 10%, P < 0.001) compared with non-T1
      transported patients. The sensitivity of the T1 protocol for severe injury was
      63% with a positive predictive value of 23%. The undertriage and overtriage rates
      for severe injury were 12% and 77%, respectively. Undertriaged patients were
      elderly with falls as the predominant mechanism of injury. CONCLUSION: The
      sensitivity and undertriage rates associated with the T1 protocol indicate the
      ongoing need for secondary triage at designated trauma centres and refinement of
      the protocol to include age as a criterion.

PMID- 22862758
TI  - Simple external rotation of the leg increases the size and accessibility of the
      femoral vein.
AB  - OBJECTIVE: To determine if external rotation of the leg increases the size and
      accessibility of the femoral vein compared with a neutral position. METHODS: One
      hundred patients presenting to a tertiary teaching hospital were prospectively
      recruited. The right common femoral vein of each subject was scanned with a
      linear probe (5-10 MHz) inferior to the inguinal ligament, with the leg in a
      neutral position and then in the externally rotated position. The transverse
      diameter of the femoral vein, the accessible diameter of the vein (lying medial
      to the femoral artery) and the depth of the vein were measured. RESULTS: The mean
      diameter of the femoral vein in the externally rotated leg was greater than with
      the leg in the neutral position (15.4 mm vs 13.8 mm); the mean difference was 1.6
      mm (95% CI 1.3-1.9). The mean accessible diameter of the femoral vein was larger
      with the leg externally rotated (13.8 mm vs 11.7 mm, mean difference 2.1 mm, 95%
      CI 1.8-2.5). The depth from the skin to the femoral vein was less with the leg in
      external rotation (20.9 mm vs 22.6 mm, mean difference 1.7 mm, 95% CI 1.2-2.2).
      The mean diameter and depth were greater in patients with overweight or obese
      body mass index (BMI) measurements in both leg positions. The increase in femoral
      vein diameter and accessibility with external rotation was observed in all BMI
      groups. CONCLUSION: The total and accessible femoral vein diameter is increased
      and the surface depth of the vein is decreased by placing the leg in external
      rotation compared with the neutral position.

PMID- 22862759
TI  - Accuracy of inter-hospital paediatric appendicitis referrals.
AB  - OBJECTIVE: Appendicitis is the most common paediatric surgical emergency. In our
      institution, the majority of inter-hospital transfers are for suspected
      appendicitis. We undertook an audit to assess the accuracy of the provisional
      diagnosis of the transferred cases. METHODS: Retrospective electronic data of a
      tertiary referral centre and a single referring regional hospital were collected
      between January 2009 and December 2010. Primary outcome of surgery, inpatient
      observation or discharge was assessed. The final appendix pathology results were
      examined. RESULTS: There were 187 paediatric surgical transfers (49% by
      ambulance) that were provisionally diagnosed as appendicitis. Of the 187 patients
      (M : F = 102 : 85, a median age of 11), 70% were admitted, 43% underwent
      appendicectomy, and only 40% had pathologically proven appendicitis. CONCLUSIONS:
      Of the surgical referrals for appendicectomy, 60% did not have appendicitis. An
      improved assessment protocol is required to reduce the margin of diagnostic error
      and transfer cost, while maintaining clinical safety.

PMID- 22862760
TI  - 'Lessons learned': A comparative case study analysis of an emergency department
      response to two burns disasters.
AB  - OBJECTIVE: The Royal Perth Hospital (RPH; Perth, Australia) has been the
      receiving facility for burns patients in two separate disasters. In 2002, RPH
      received 28 severely injured burns patients after the Bali bombing, and in 2009
      RPH received 23 significantly burnt patients as a result of an explosion on board
      a foreign vessel in the remote Ashmore Reef Islands (840 km west of Darwin). The
      aim of this paper is to identify the interventions developed following the Bali
      bombing in 2002 and review their effectiveness of their implementation in the
      subsequent burns disaster. METHODS: A comparative case study analysis using a
      standardised approach was used to describe context with debrief reports and ED
      photographs from both disasters used for evaluation. RESULTS: The implementation
      of regular ED disaster response planning and training, early Code Brown
      notification of the entire hospital with regular updates, early clearing of
      inpatient beds, use of Short Message Service to communicate regularly with ED
      staff, control of the public and media access to the ED, visual identification of
      staff within the ED, early panendoscopy to ascertain intubation needs, and senior
      clinical decision makers in all areas of the ED were all acknowledged as
      effective based on the debrief reports. There was a reduction in ED length of
      stay (150 to 55 min) and no deaths occurred; however, quantitative analysis can
      only be suggestive rather than a direct measure of improvement given the
      likelihood of other system changes. CONCLUSION: There were a number of lessons
      observed from the Bali experience in 2002 that have led to improvements in
      practice and lessons learned.

PMID- 22862761
TI  - Initial resuscitation for Australasian Triage Scale 2 patients in a Nepalese
      emergency department.
AB  - OBJECTIVES: Triage is recognized as important in providing timely care to
      emergency patients. However, systematic triage is only practised in two EDs in
      Nepal. The first objective of this study was to assess the performance of one of
      these departments in seeing triaged patients in a timely fashion. Second, an
      epidemiological survey of patients presenting to the ED was performed to describe
      the conditions seen and initial resuscitation undertaken. METHODS: We performed a
      descriptive cross-sectional study in the ED of B.P. Koirala Institute of Health
      Sciences, eastern Nepal where the Australasian Triage Scale (ATS) is used. One
      hundred and sixty patients triaged as ATS 2 were recruited. The time taken for
      the duty doctor to see the patient was noted. The presenting problems, vital
      signs and level of consciousness were measured at presentation. The resuscitation
      measures were recorded. RESULTS: The mean waiting time was 2.1 +/- 1.7 min with a
      range of 1-10 min, which meets the benchmark for ATS 2. At triage, the most
      common presenting problems were circulatory shock (23.1%), altered consciousness
      (21%), respiratory difficulty (16.9%) and poisoning (15%). Oxygen, i.v. fluids
      and antibiotics were the most common therapies used in the initial resuscitation
      of patients. CONCLUSION: Patients triaged as ATS 2 were seen in a timely fashion.
      Seriously ill patients requiring resuscitation present commonly to this ED. This
      is a big challenge for junior doctors. Improved training, treatment protocols and
      equipment are needed to help manage this burden.

PMID- 22862762
TI  - International emergency medicine: how to train for it.
AB  - This article provides background information about the emerging field of
      international emergency medicine (IEM) and how emergency physicians in
      Australasia can participate in its practice and development. It reviews the seven
      key areas of knowledge and skills involved in the practice of IEM as put forward
      by US fellowship programmes: (i) Emergency Medicine Systems Development; (ii)
      Humanitarian Relief; (iii) Disaster Management; (iv) Public Health; (v) Travel
      and Field Medicine; (vi) Programme Administration; and (vii) Academic Skills.
      Current obstacles to the development of similar programmes in Australasia are
      explored and identified as primarily financial. Means by which individuals can
      fund and engage in IEM activities are proposed. This article provides a reference
      of domestic and international IEM training resources that can be obtained by
      Australasian emergency physicians and trainees today.

PMID- 22862763
TI  - National Coroners Information System: a valuable source of lessons for emergency
      medicine.
AB  - OBJECTIVE: To interrogate the National Coroners Information System (NCIS) to
      determine the recurrent themes among coroners' recommendations that aimed to
      increase the safety of ED care. METHODS: This was a retrospective analysis of
      NCIS closed cases, from Queensland, New South Wales, Tasmania, Victoria,
      Australian Capital Territory, South Australia and North Territory, entered since
      its inception in 2000. The keyword 'emergency department' returned 1645 cases, of
      which 180 were found to be relevant. The primary outcomes were the number and
      nature of cases where recommendations for improvements in ED care had been made
      and the recurrent themes of these recommendations that could inform education
      initiatives. RESULTS: Of the 180 cases, 108 (60.0%) were of deceased men and
      subject age ranged from 2 days to 91 years. The commonest causes of death were
      trauma (26.7%), infection (24.4%), cardiac events (15.0%) and poisoning (8.9%).
      No coronial recommendations were required in 19 cases. For the remainder,
      recommendation themes related to issues of risk management/medico-legal,
      diagnostic/therapeutic error, education, documentation/communication and re
      presentation. The themes associated with the different doctor designations
      (consultant, registrar, resident/intern) were similar, although registrars and
      residents/interns tended towards more diagnostic/therapeutic errors. The themes
      associated with hospital type (referral, urban, regional/rural) were also
      similar. Although theme analysis is important, some individual cases were
      particularly instructive. CONCLUSION: The NCIS data theme analysis identifies
      important high-risk patients and presenting complaints. These should be
      incorporated into emergency physician training. EDs should review the coronial
      recommendations to ensure that, where possible, they have been adopted.

PMID- 22862764
TI  - Toxic cocktail: methanol poisoning in a tourist to Indonesia.
AB  - Methanol poisoning has become very uncommon in Australasia with regulations that
      have reduced its retail availability. This report describes a young tourist who
      developed sudden onset visual failure and rapid breathing 2 days after ingestion
      of a complimentary local drink called Arrack when travelling in Indonesia. She
      presented to a hospital in New Zealand with severe metabolic acidosis and a
      highly toxic methanol level at 17 mmol/L. The cocktail was consumed at a popular
      tourist bar but is likely to have been mixed from home-brewed or 'moonshine'
      alcohol tainted with methanol. The aetiology of methanol poisoning, its optic
      toxicology and therapeutic measures are discussed, as is the concerning number of
      methanol poisoning cases among tourists to Indonesia over recent years.

PMID- 22862765
TI  - Terson's syndrome: subarachnoid haemorrhage presenting as sudden visual loss.
AB  - Subarachnoid haemorrhage is a condition that usually presents with headache and
      altered mental state. We report the case of a 50-year-old man with subarachnoid
      haemorrhage who presented with Terson's syndrome. This is a condition where there
      is retinal or vitreous haemorrhage secondary to subarachnoid or subdural
      haemorrhage.

PMID- 22862766
TI  - Acute paraspinal compartment syndrome as an unusual cause of severe low back
      pain.
AB  - This report describes a case of acute paraspinal compartment syndrome in a 25
      year-old man. The diagnosis was significantly delayed, perhaps to some extent
      because of the rarity of the condition. The patient was managed with forced
      diuresis, analgesia and hyperbaric oxygen therapy. The discussion addresses an
      unusual site for compartment syndrome and a diagnosis not commonly considered in
      the differential of low back pain. Treatment options are discussed and we review
      previous published case reports.

PMID- 22862767
TI  - Vascular hyperpermeability in pulmonary decompression illness: 'the chokes'.
AB  - Decompression illness (DCI) develops during or after diving. Pulmonary
      decompression illness ('Chokes') is rarely seen because the affected individual
      usually dies in the water. We encountered a rare and interesting case. A 60-year
      old man complained of leg pain after diving. Despite rapid transfer to a nearby
      hospital, advanced respiratory failure and shock had set in. He was then
      transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of
      his poor general condition, we initially treated him in the intensive care unit
      without HBOT, where he showed extreme hyperpermeability and a high level of serum
      procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe
      intravascular dehydration and shock status remained. We assume that the injured
      endothelial cells induced vascular hyperpermeability and increased levels of
      inflammatory cytokines leading to the high serum PCT level. PCT might be a useful
      stress marker of endothelial damage and severity in DCI, including Chokes.

PMID- 22862768
TI  - Australasian College for Emergency Medicine, Emergency Medicine Australasia and
      social media.

PMID- 22862769
TI  - Missing data in the electronic medical record era.

PMID- 22862770
TI  - Acute ST-elevation myocardial infarction in a 24-year-old woman with atheromatous
      coronary artery disease: comment.

PMID- 22862772
TI  - Is she really 'one of the youngest' with an acute myocardial infarction?

PMID- 22862774
TI  - Knowledge, attitude, and practices about the seasonal influenza vaccination among
      healthcare workers in Srinagar, India.
AB  - BACKGROUND: Healthcare workers (HCWs) universally have a poor uptake of influenza
      vaccination. However, no data are available from India. OBJECTIVE: To explore
      knowledge, attitudes, and practices associated with influenza vaccination in HCWs
      in a temperate climate area in northern India. PATIENTS AND METHODS: A self
      administered questionnaire was offered to all HCWs in three major hospitals of
      Srinagar and information sought on motivations, perceptions, preferences and
      practices regarding influenza vaccination. RESULTS: Of the 1750 questionnaires
      received, 1421 (81%) were returned. Only 62 (4.4%) HCWs had ever received
      influenza vaccination even as 1348 (95%) believed that influenza poses adverse
      potential consequences for themselves or their contacts; 1144 (81%) were aware of
      a vaccine against influenza and 830 (58%) of its local availability. Reasons
      cited by 1359 participants for not being vaccinated included ignorance about
      vaccine availability (435; 32%), skepticism about efficacy (248; 18%), busy
      schedule (166; 12%), fear of side effects (70; 4%), and a perception of not being
      at-risk (82; 6%). Sixty-one percent (865) believed that vaccine programs are
      motivated by profit. Eighty-eight percent opined for mandatory vaccination for
      HCWs caring for the high-risk patients, as a part of 'employee health program'.
      Most of the participants intended to get vaccinated in the current year even as
      684 (48%) held that vaccines could cause unknown illness and 444 (31%) believed
      their adverse effects to be underreported. CONCLUSION: Influenza vaccination
      coverage among HCWs is dismally low in Srinagar; poor knowledge of vaccine
      availability and misperceptions about vaccine effectiveness, fear of adverse
      effects and obliviousness to being-at-risk being important barriers.
      Multifaceted, adaptable measures need to be invoked urgently to increase the
      coverage.

PMID- 22862775
TI  - Conventional and stuffed Bergman-type phases in the Na-Au-T (T = Ga, Ge, Sn)
      systems: syntheses, structures, coloring of cluster centers, and Fermi sphere
      brillouin zone interactions.
AB  - Bergman-type phases in the Na-Au-T (T = Ga, Ge, and Sn) systems were synthesized
      by solid-state means and structurally characterized by single-crystal X-ray
      diffraction studies. Two structurally related (1/1) Bergman phases were found in
      the Na-Au-Ga system: (a) a conventional Bergman-type (CB) structure,
      Na(26)Au(x)Ga(54-x), which features empty innermost icosahedra, as refined with x
      = 18.1 (3), Im3, a = 14.512(2) A, and Z = 2; (b) a stuffed Bergman-type (SB)
      structure, Na(26)Au(y)Ga(55-y), which contains Ga-centered innermost icosahedra,
      as refined with y = 36.0 (1), Im3, a = 14.597(2) A, and Z = 2. Although these two
      subtypes have considerable phase widths along with respective tie lines at Na ~
      32.5 and 32.1 atom %, they do not merge into a continuous solid solution. Rather,
      a quasicrystalline phase close to the Au-poor CB phase and an orthorhombic
      derivative near the Au-rich SB phase lie between them. In contrast, only Au-rich
      SB phases exist in the Ge and Sn systems, in which the innermost icosahedra are
      centered by Au rather than Ge or Sn. These were refined for
      Na(26)Au(40.93(5))Ge(14.07(5)) (Im3, a = 14.581(2) A, and Z = 2) and
      Na(26)Au(39.83(6))Sn(15.17(6)) (Im3, a = 15.009(2) A, and Z = 2), respectively.
      Occupations of the centers of Bergman clusters are rare. Such centering and
      coloring correlate with the sizes of the neighboring icosahedra, the size ratios
      between electropositive and electronegative components, and the values of the
      average valence electron count per atom (e/a). Theoretical calculations revealed
      that all of these phases are Hume-Rothery phases, with evident pseudogaps in the
      density of states curves that arise from the interactions between Fermi surface
      and Brillouin zone boundaries corresponding to a strong diffraction intensity.

PMID- 22862776
TI  - Rational improvement of the engineered isobutanol-producing Bacillus subtilis by
      elementary mode analysis.
AB  - BACKGROUND: Isobutanol is considered as a leading candidate for the replacement
      of current fossil fuels, and expected to be produced biotechnologically. Owing to
      the valuable features, Bacillus subtilis has been engineered as an isobutanol
      producer, whereas it needs to be further optimized for more efficient production.
      Since elementary mode analysis (EMA) is a powerful tool for systematical analysis
      of metabolic network structures and cell metabolism, it might be of great
      importance in the rational strain improvement. RESULTS: Metabolic network of the
      isobutanol-producing B. subtilis BSUL03 was first constructed for EMA.
      Considering the actual cellular physiological state, 239 elementary modes (EMs)
      were screened from total 11,342 EMs for potential target prediction. On this
      basis, lactate dehydrogenase (LDH) and pyruvate dehydrogenase complex (PDHC) were
      predicted as the most promising inactivation candidates according to flux
      flexibility analysis and intracellular flux distribution simulation. Then, the in
      silico designed mutants were experimentally constructed. The maximal isobutanol
      yield of the LDH- and PDHC-deficient strain BSUL05 reached 61% of the theoretical
      value to 0.36 +/- 0.02 C-mol isobutanol/C-mol glucose, which was 2.3-fold of
      BSUL03. Moreover, this mutant produced approximately 70 % more isobutanol to the
      maximal titer of 5.5 +/- 0.3 g/L in fed-batch fermentations. CONCLUSIONS: EMA was
      employed as a guiding tool to direct rational improvement of the engineered
      isobutanol-producing B. subtilis. The consistency between model prediction and
      experimental results demonstrates the rationality and accuracy of this EMA-based
      approach for target identification. This network-based rational strain
      improvement strategy could serve as a promising concept to engineer efficient B.
      subtilis hosts for isobutanol, as well as other valuable products.

PMID- 22862777
TI  - Extraordinary control of terahertz beam reflectance in graphene electro
      absorption modulators.
AB  - We demonstrate a graphene-based electro-absorption modulator achieving
      extraordinary control of terahertz reflectance. By concentrating the electric
      field intensity in an active layer of graphene, an extraordinary modulation depth
      of 64% is achieved while simultaneously exhibiting low insertion loss (~2 dB),
      which is remarkable since the active region of the device is atomically thin.
      This modulator performance, among the best reported to date, indicates the
      enormous potential of graphene for terahertz reconfigurable optoelectronic
      devices.

PMID- 22862778
TI  - Investigating phenotypic heterogeneity in children with autism spectrum disorder:
      a factor mixture modeling approach.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is characterized by notable phenotypic
      heterogeneity, which is often viewed as an obstacle to the study of its etiology,
      diagnosis, treatment, and prognosis. On the basis of empirical evidence, instead
      of three binary categories, the upcoming edition of the DSM 5 will use two
      dimensions - social communication deficits (SCD) and fixated interests and
      repetitive behaviors (FIRB) - for the ASD diagnostic criteria. Building on this
      proposed DSM 5 model, it would be useful to consider whether empirical data on
      the SCD and FIRB dimensions can be used within the novel methodological framework
      of Factor Mixture Modeling (FMM) to stratify children with ASD into more
      homogeneous subgroups. METHODS: The study sample consisted of 391 newly diagnosed
      children (mean age 38.3 months; 330 males) with ASD. To derive subgroups, data
      from the Autism Diagnostic Interview-Revised indexing SCD and FIRB were used in
      FMM; FMM allows the examination of continuous dimensions and latent classes
      (i.e., categories) using both factor analysis (FA) and latent class analysis
      (LCA) as part of a single analytic framework. RESULTS: Competing LCA, FA, and FMM
      models were fit to the data. On the basis of a set of goodness-of-fit criteria, a
      'two-factor/three-class' factor mixture model provided the overall best fit to
      the data. This model describes ASD using three subgroups/classes (Class 1: 34%,
      Class 2: 10%, Class 3: 56% of the sample) based on differential severity
      gradients on the SCD and FIRB symptom dimensions. In addition to having different
      symptom severity levels, children from these subgroups were diagnosed at
      different ages and were functioning at different adaptive, language, and
      cognitive levels. CONCLUSIONS: Study findings suggest that the two symptom
      dimensions of SCD and FIRB proposed for the DSM 5 can be used in FMM to stratify
      children with ASD empirically into three relatively homogeneous subgroups.

PMID- 22862779
TI  - Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and
      in vivo.
AB  - Agents with selective toxicity to hypoxic cells have shown promise as adjuncts to
      radiotherapy. Our previous studies showed that the bioreductive alkylating agent
      KS119 had an extremely large differential toxicity to severely hypoxic and
      aerobic cells in cell culture, and was effective in killing the hypoxic cells of
      EMT6 mouse mammary tumors in vivo. However, the limited solubility of that
      compound precluded its development as an anticancer drug. Here we report our
      initial studies with KS119W, a water-soluble analog of KS119. The cytotoxicity of
      KS119W to EMT6 cells in vitro was similar to that of KS119, with both agents
      producing only minimal cytotoxicity to aerobic cells even after intensive
      treatments, while producing pronounced cytotoxicity to oxygen-deficient cells.
      This resulted in large differentials in the toxicities to hypoxic and aerobic
      cells (>1,000-fold at 10 MUM). Low pH had only minimal effects on the
      cytotoxicity of KS119W. Under hypoxic conditions, EMT6 cells transfected to
      express high levels of either human or mouse versions of the repair protein O(6)
      alkylguanine-DNA alkyltransferase, which is also known as O(6)-methylguanine DNA
      methyltransferase, were much more resistant to KS119W than parental EMT6 cells
      lacking O(6)-alkylguanine-DNA alkyltransferase, confirming the importance of DNA
      O-6-alkylation to the cytotoxicity of this agent. Studies with EMT6 tumors in
      BALB/c Rw mice using both tumor cell survival and tumor growth delay assays
      showed that KS119W was effective as an adjunct to irradiation for the treatment
      of solid tumors in vivo, producing additive or supra-additive effects in most
      combination regimens for which the interactions could be evaluated. Our findings
      encourage additional preclinical studies to examine further the antineoplastic
      effects of KS119W alone and in combination with radiation, and to examine the
      pharmacology and toxicology of this new bioreductive alkylating agent so that its
      potential for clinical use as an adjuvant to radiotherapy can be evaluated.

PMID- 22862780
TI  - Radiation and smoking effects on lung cancer incidence by histological types
      among atomic bomb survivors.
AB  - While the risk of lung cancer associated separately with smoking and radiation
      exposure has been widely reported, it is not clear how smoking and radiation
      together contribute to the risk of specific lung cancer histological types. With
      individual smoking histories and radiation dose estimates, we characterized the
      joint effects of radiation and smoking on type-specific lung cancer rates among
      the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404
      cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer
      incident cases were diagnosed and classified by histological type. Poisson
      regression methods were used to estimate excess relative risks under several
      interaction models.   Adenocarcinoma (636 cases), squamous-cell carcinoma (330)
      and small-cell carcinoma (194) made up 90% of the cases with known histology.
      Both smoking and radiation exposure significantly increased the risk of each
      major lung cancer histological type. Smoking-associated excess relative risks
      were significantly larger for small-cell and squamous-cell carcinomas than for
      adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation
      (for never-smokers at age 70 after radiation exposure at age 30) were estimated
      as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3
      1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a
      model allowing radiation effects to vary with levels of smoking, the nature of
      the joint effect of smoking and radiation showed a similar pattern for different
      histological types in which the radiation-associated excess relative risk tended
      to be larger for moderate smokers than for heavy smokers. However, in contrast to
      analyses of all lung cancers as a group, such complicated interactions did not
      describe the data significantly better than either simple additive or
      multiplicative interaction models for any of the type-specific analyses.

PMID- 22862781
TI  - Phenotypic effects of cattle mitochondrial DNA in American bison.
AB  - Hybridization between endangered species and more common species is a significant
      problem in conservation biology because it may result in extinction or loss of
      adaptation. The historical reduction in abundance and geographic distribution of
      the American plains bison (Bison bison bison) and their recovery over the last
      125 years is well documented. However, introgression from domestic cattle (Bos
      taurus) into the few remaining bison populations that existed in the late 1800s
      has now been identified in many modern bison herds. We examined the phenotypic
      effect of this ancestry by comparing weight and height of bison with cattle or
      bison mitochondrial DNA (mtDNA) from Santa Catalina Island, California (U.S.A.),
      a nutritionally stressful environment for bison, and of a group of age-matched
      feedlot bison males in Montana, a nutritionally rich environment. The
      environmental and nutritional differences between these 2 bison populations were
      very different and demonstrated the phenotypic effect of domestic cattle mtDNA in
      bison over a broad range of conditions. For example, the average weight of
      feedlot males that were 2 years of age was 2.54 times greater than that of males
      from Santa Catalina Island. In both environments, bison with cattle mtDNA had
      lower weight compared with bison with bison mtDNA, and on Santa Catalina Island,
      the height of bison with cattle mtDNA was lower than the height of bison with
      bison mtDNA. These data support the hypothesis that body size is smaller and
      height is lower in bison with domestic cattle mtDNA and that genomic integrity is
      important for the conservation of the American plains bison.

PMID- 22862782
TI  - Risk of mortality and nursing home institutionalization after injury.
AB  - OBJECTIVES: To evaluate the effects of unintentional injuries on the risks of
      nursing home institutionalization and mortality in older adults. DESIGN: A
      retrospective analysis of data from the Medicare Current Beneficiary Survey, a
      nationally representative survey of Medicare beneficiaries. SETTING:
      Noninstitutionalized community residents. PARTICIPANTS: Older adult panel members
      (N = 12,031) with continuous Medicare eligibility not enrolled in managed care in
      a cohort starting between 1998 and 2001. MEASUREMENTS: Cox regression and
      competing risk survival models were estimated using time-varying injury-status
      dummy variables and control variables for outcomes measured as time until death
      and institutionalization, respectively. RESULTS: Almost 4% of persons were
      institutionalized, 15% died, 14% had a sentinel injury, and 3% had two or more
      minor nonsentinel injuries within 1-year period. Persons hospitalized for
      sentinel injury had elevated institutionalization and mortality risks during an
      injury episode and after the episode ended. Persons receiving outpatient
      treatment for sentinel injuries had elevated institutionalization risk during
      injury episodes (subhazard ratio [SHR] = 6.78, 95% confidence interval [CI] =
      3.72-12.37) and elevated mortality risk after episodes (hazard ratio [HR] = 1.60,
      95% CI = 1.28-2.00). Persons with multiple minor nonsentinel injuries within a
      year also had elevated mortality (HR = 1.56, 95% CI = 1.15-2.11) and
      institutionalization (SHR = 3.55, 95% CI = 2.25-5.67) risks. CONCLUSION:
      Mortality and institutionalization risks extend well beyond the acute episode of
      treatment for sentinel and repeated minor injuries. More research is needed on
      longer-term health outcomes of injury survivors to inform development of evidence
      based quality-of-care indicators.

PMID- 22862783
TI  - Vaccines for the elderly.
AB  - Vaccination is the most efficient strategy to prevent infectious disease. The
      increased vulnerability to infection of the elderly makes them a particularly
      important target population for vaccination. However, most vaccines are less
      immunogenic and efficient in the elderly because of age-related changes in the
      immune system. Vaccination against influenza, Streptococcus pneumoniae and
      varicella zoster virus is recommended for the elderly in many countries. Various
      strategies such as the use of adjuvants and novel administration routes are
      pursued to improve influenza vaccination for the elderly and recent developments
      in the field of pneumococcal vaccination led to the licensure of protein
      conjugated polysaccharide vaccines containing up to 13 serotypes. As antibody
      titres are generally lower in the elderly and-particularly for inactivated
      vaccines-decline fast in the elderly, regular booster immunizations, for example
      against tetanus, diphtheria and, in endemic areas, tick-borne encephalitis, are
      essential during adulthood to ensure protection of the elderly. With increasing
      health and travel opportunities in old age the importance of travel vaccines for
      persons over the age of 60 is growing. However, little is known about
      immunogenicity and efficacy of travel vaccines in this age group. Despite major
      advances in the field of vaccinology over the last decades, there are still
      possibilities for improvement concerning vaccines for the elderly. Novel
      approaches, such as viral vectors for antigen delivery, DNA-based vaccines and
      innovative adjuvants, particularly toll-like receptor agonists, will help to
      achieve optimal protection against infectious diseases in old age.

PMID- 22862784
TI  - Inaccurate identification of rotavirus genotype G9 as genotype G3 strains due to
      primer mismatch.
AB  - Reverse transcription (RT)-PCR is now the standard method for typing group A
      rotaviruses (RVA) to monitor the circulating genotypes in a population. Selection
      of primers that can accurately type the circulating genotypes is crucial in the
      context of vaccine introduction and correctly interpreting the impact of
      vaccination on strain distribution. To our knowledge this study is the first
      report from Asia of misidentification of genotype G9 as G3 due to a primer
      template mismatch. We tested two published G-genotype specific primers sets,
      designed by Gouvea and colleagues (Set A) and Iturriza-Gomara and colleagues (Set
      B) on RVA from Hong Kong and Sri Lanka. Among 52 rotaviruses typed as G3 by set A
      primers, 36 (69.2%) were identified as G9 by nucleotide sequencing and set B
      primers. Moreover, of 300 rotaviruses tested, 28.3% were untypable by set A
      primers whereas only 12.3% were untypable by set B primers. Our findings
      reinforce the need to periodically monitor the primers used for RVA genotyping.

PMID- 22862785
TI  - Resident phenotypically modulated vascular smooth muscle cells in healthy human
      arteries.
AB  - Vascular interstitial cells (VICs) are non-contractile cells with filopodia
      previously described in healthy blood vessels of rodents and their function
      remains unknown. The objective of this study was to identify VICs in human
      arteries and to ascertain their role. VICs were identified in the wall of human
      gastro-omental arteries using transmission electron microscopy. Isolated VICs
      showed ability to form new and elongate existing filopodia and actively change
      body shape. Most importantly sprouting VICs were also observed in cell dispersal.
      RT-PCR performed on separately collected contractile vascular smooth muscle cells
      (VSMCs) and VICs showed that both cell types expressed the gene for smooth muscle
      myosin heavy chain (SM-MHC). Immunofluorescent labelling showed that both VSMCs
      and VICs had similar fluorescence for SM-MHC and alphaSM-actin, VICs, however,
      had significantly lower fluorescence for smoothelin, myosin light chain kinase, h
      calponin and SM22alpha. It was also found that VICs do not have cytoskeleton as
      rigid as in contractile VSMCs. VICs express number of VSMC-specific proteins and
      display features of phenotypically modulated VSMCs with increased migratory
      abilities. VICs, therefore represent resident phenotypically modulated VSMCs that
      are present in human arteries under normal physiological conditions.

PMID- 22862786
TI  - Composition and physiological function of the chloroplast NADH dehydrogenase-like
      complex in Marchantia polymorpha.
AB  - The chloroplast NADH dehydrogenase-like (NDH) complex mediates cyclic electron
      transport and chloro-respiration and consists of five sub-omplexes, which in
      angiosperms further associate with photosystem I (PSI) to form a super-complex.
      In Marchantia polymorpha, 11 plastid-encoded subunits and all the nuclear-encoded
      subunits of the A, B, membrane and ferredoxin-binding sub-complexes are
      conserved. However, it is unlikely that the genome of this liverwort encodes
      Lhca5 and Lhca6, both of which mediate NDH-PSI super-complex formation. It is
      also unlikely that the subunits of the lumen sub-complex, PnsL1-L4, are encoded
      by the genome. Consistent with this in silico prediction, the results of blue
      native gel electrophoresis showed that NDH subunits were detected in a protein
      complex with lower molecular mass in Marchantia than the NDH-PSI super-complex in
      Arabidopsis. Using the plastid transformation technique, we knocked out the ndhB
      gene in Marchantia. Although the wild-type genome copies were completely
      segregated out, the DeltandhB lines grew like the wild-type photoautotrophically.
      A post-illumination transient increase in chlorophyll fluorescence, which
      reflects NDH activity in vivo in angiosperms, was absent in the thalli of the
      DeltandhB lines. In ruptured chloroplasts, antimycin A-insensitive, and
      ferredoxin-dependent plastoquinone reduction was impaired, suggesting that
      chloroplast NDH mediates similar electron transport in Marchantia and
      Arabidopsis, despite its possible difference in structure. As in angiosperms,
      linear electron transport was not strongly affected in the DeltandhB lines.
      However, the plastoquinone pool was slightly more reduced at low light intensity,
      suggesting that chloroplast NDH functions in redox balancing of the inter system,
      especially under low light conditions.

PMID- 22862788
TI  - Immunization with Leishmania vaccine-alum-BCG and montanide ISA 720 adjuvants
      induces low-grade type 2 cytokines and high levels of IgG2 subclass antibodies in
      the vervet monkey (Chlorocebus aethiops) model.
AB  - The availability of hundreds of adjuvants has prompted a need for identifying
      rational standards for the selection of adjuvant formulation based on sound
      immunological principles for human vaccines. As cytokines elaborated by activated
      T cells are required for the regulation of isotype switch during B-cell
      development, a study of Th2 cytokines and subclass distribution of the antibodies
      may shed new light on the processes involved in the polarization of the immune
      responses during vaccination studies. The aim of this study was to identify an
      appropriate Leishmania vaccine adjuvant based on low Th2 cytokine and high value
      IgG2 antibody responses. Groups of vervet monkeys were immunized with Leishmania
      donovani sonicate antigen (Ag) alone or in conjunction with alum-BCG (AlBCG),
      monophosphoryl lipid A (MPL) or montanide ISA 720 (MISA) as adjuvants. Following
      three time point intradermal injections on days 0, 28 and 42, IL-4, IL-10 and IgG
      antibody subclasses were quantified by enzyme-linked immunosorbent assay (ELISA)
      and data analysed by one-way analysis of variance, Tukey-Kramer test and
      Spearman's rank correlation analysis. Results indicated relatively higher IL-4
      and IL-10 cytokine responses following MPL + Ag as compared to AlBCG + Ag or MISA
      + Ag immunization. There was a positive significant correlation between IL-4 and
      IL-10 levels (r = 1.000; P = 0.0167). Significantly higher IgG2 antibody
      responses were associated with either AlBCG + Ag or MISA + Ag as compared to MPL
      + Ag immunization (P < 0.05). The study concludes that both AlBCG and MISA may be
      used in Leishmania vaccine studies that favour low Th2 cytokine and strong IgG2
      antibody responses.

PMID- 22862787
TI  - Subgroups of musculoskeletal pain patients and their psychobiological patterns -
      the LOGIN study protocol.
AB  - BACKGROUND: Pain conditions of the musculoskeletal system are very common and
      have tremendous socioeconomic impact. Despite its high prevalence,
      musculoskeletal pain remains poorly understood and predominantly non-specifically
      and insufficiently treated.The group of chronic musculoskeletal pain patients is
      supposed to be heterogeneous, due to a multitude of mechanisms involved in
      chronic pain. Psychological variables, psychophysiological processes, and
      neuroendocrine alterations are expected to be involved. Thus far, studies on
      musculoskeletal pain have predominantly focused on the general aspects of pain
      processing, thus neglecting the heterogeneity of patients with musculoskeletal
      pain. Consequently, there is a need for studies that comprise a multitude of
      mechanisms that are potentially involved in the chronicity and spread of pain.
      This need might foster research and facilitate a better pathophysiological
      understanding of the condition, thereby promoting the development of specific
      mechanism-based treatments for chronic pain. Therefore, the objectives of this
      study are as follows: 1) identify and describe subgroups of patients with
      musculoskeletal pain with regard to clinical manifestations (including mental co
      morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct
      plasma levels of pain-related parameters due to different underlying mechanisms
      can be distinguished in various subgroups of pain patients. METHODS/DESIGN: We
      will examine a population-based chronic pain sample (n = 100), a clinical
      tertiary care sample (n = 100) and pain-free patients with depression or post
      traumatic stress disorder and pain-free healthy controls (each n = 30,
      respectively). The samples will be pain localisation matched by sex and age to
      the population-based sample. Patients will undergo physical examination and
      thorough assessments of mental co-morbidity (including psychological trauma),
      perceptual and central sensitisation (quantitative sensory testing), descending
      inhibition (conditioned pain modulation, the diffuse noxious inhibitory control
      like effect), as well as measurement of the plasma levels of nerve growth factor
      and endocannabinoids. DISCUSSION: The identification of the underlying
      pathophysiologic mechanisms in different subgroups of chronic musculoskeletal
      pain patients will contribute to a mechanism-based subgroup classification. This
      will foster the development of mechanism-based treatments and holds promise to
      treat patients more sufficient.

PMID- 22862789
TI  - Intra-articular use of a medical device composed of hyaluronic acid and
      chondroitin sulfate (Structovial CS): effects on clinical, ultrasonographic and
      biological parameters.
AB  - BACKGROUND: This pilot open noncontrolled study was designed to assess the
      efficacy of intra-articular injections of a solution combining hyaluronic acid
      (HA) and chondroitin sulphate (CS) in the treatment of outpatients affected by
      knee osteoarthrosis. FINDINGS: Thirty patients with knee OA have been included.
      The primary objective was to assess clinical efficacy as measured by pain and
      Lequesne's index. Secondary objectives were to assess potential effect of the
      treatment on ultrasound parameters, safety and biomarkers of cartilage metabolism
      and joint inflammation. After a selection visit (V1), the study treatment was
      administered 3 times on a weekly basis (V2, V3, V4). Follow-up was planned 6 (V5)
      and 12 weeks (V6) after the first intra-articular injection. Efficacy results
      showed a reduction in mean pain at V3 and V6 and in functional impairment, the
      most marked changes being measured at the two follow-up visits (V5 and V6).
      Although statistical significance was not achieved due to small sample size, a
      clear tendency towards improvement was detectable for ultrasound assessments as
      well as biomarkers. Except for a mild injection site hematoma for which the drug
      causal relationship could not be excluded, no adverse effect of clinical
      relevance was recorded during the study. CONCLUSION: Although this pilot study
      was performed according to an open design only, the ultrasound as well as
      biomarkers changes strongly suggest a non-placebo effect. These preliminary
      results call now for a randomized controlled study to confirm the clinical
      relevance of the observed results. TRIAL REGISTRATION: #ISRCTN91883031.

PMID- 22862790
TI  - Evaluation of the pharmacokinetics, preclinical, and clinical efficacy of 
      lenalidomide  for the treatment of multiple myeloma.
AB  - INTRODUCTION: Lenalidomide is an oral immunomodulatory drug, which was recently
      introduced for the treatment of multiple myeloma (MM). It has been used for the
      treatment of newly diagnosed and relapsed MM patients, as both maintenance and
      preventive therapy. Available data show a progression-free survival and overall
      survival improvement associated with this drug. AREAS COVERED: Efficacy results
      of lenalidomide in Phase I, II, and III trials in MM are reported herein. The
      recent use of lenalidomide as maintenance and preventive therapy is described. An
      overview of the most important adverse events is also presented, such as
      myelosuppression, thromboembolic events, fatigue, dermatologic toxicity,
      infections, teratogenic potential, and second primary malignancies. The
      literature reviewed consists of clinical trials published from 2001 to 2012.
      EXPERT OPINION: Lenalidomide is one of the most important therapeutic agents for
      MM treatment. Various trials have confirmed its remarkable anticancer activity,
      alone or combined with high- or low-dose dexamethasone, or other drugs.
      Lenalidomide-related adverse events can be controlled with dose reductions,
      supportive therapy, and appropriate prophylaxis.

PMID- 22862791
TI  - Bats and bacterial pathogens: a review.
AB  - The occurrence of emerging infectious diseases and their relevance to human
      health has increased the interest in bats as potential reservoir hosts and
      vectors of zoonotic pathogens. But while previous and ongoing research activities
      predominantly focused on viral agents, the prevalence of pathogenic bacteria in
      bats and their impact on bat mortality have largely neglected. Enteric pathogens
      found in bats are often considered to originate from the bats' diet and foraging
      habitats, despite the fact that little is known about the actual ecological
      context or even transmission cycles involving bats, humans and other animals like
      pets and livestock. For some bacterial pathogens common in human and animal
      diseases (e.g. Pasteurella, Salmonella, Escherichia and Yersinia spp.), the
      pathogenic potential has been confirmed for bats. Other bacterial pathogens (e.g.
      Bartonella, Borrelia and Leptospira spp.) provide evidence for novel species that
      seem to be specific for bat hosts but might also be of disease importance in
      humans and other animals. The purpose of this review is to summarize the current
      knowledge of bacterial pathogens identified in bats and to consider factors that
      might influence the exposure and susceptibility of bats to bacterial infection
      but could also affect bacterial transmission rates between bats, humans and other
      animals.

PMID- 22862792
TI  - Use of a blood gas analyzer and a laboratory autoanalyzer in routine practice to
      measure electrolytes in intensive care unit patients.
AB  - BACKGROUND: Electrolyte values are measured in most critically ill intensive care
      unit (ICU) patients using both an arterial blood gas analyzer (ABG) and a central
      laboratory auto-analyzer (AA). The aim of the present study was to investigate
      whether electrolyte levels assessed using an ABG and an AA were equivalent; data
      on sodium and potassium ion concentrations were examined. METHODS: We
      retrospectively studied patients hospitalized in the ICU between July and August
      2011. Of 1,105 test samples, we identified 84 instances of simultaneous sampling
      of arterial and venous blood, where both Na+ and K+ levels were measured using a
      pHOx Stat Profile Plus L blood gas analyzer (Nova Biomedical, Waltham MA, USA)
      and a Roche Modular P autoanalyzer (Roche Diagnostics, Mannheim, Germany).
      Statistical measures employed to compare the data included Spearman's correlation
      coefficients, paired Student's t-tests, Deming regression analysis, and Bland
      Altman plots. RESULTS: The mean sodium concentration was 138.1 mmol/L (SD 10.2
      mmol/L) using the ABG and 143.0 mmol/L (SD 10.5) using the AA (p < 0.001). The
      mean potassium level was 3.5 mmol/L (SD 0.9 mmol/L) using the ABG and 3.7 mmol/L
      (SD 1.0 mmol/L) using the AA (p < 0.001). The extent of inter-analyzer agreement
      was unacceptable for both K+ and Na+, with biases of 0.150-0.352 and -0.97-10.05
      respectively; the associated correlation coefficients were 0.88 and 0.90.
      CONCLUSIONS: We conclude that the ABG and AA do not yield equivalent Na+ and K+
      data. Concordance between ABG and AA should be established prior to introduction
      of new ABG systems.

PMID- 22862794
TI  - Simultaneous assay of activated platelet count and platelet-activating capacity
      by P-selectin detection using K2-EDTA-treated whole blood for antiplatelet
      agents.
AB  - INTRODUCTION: It is well recognized that examinations of activated platelets
      (aPLTs) and platelet-activating capacity are very important to observe and
      prevent embolic diseases (events) such as ischemic stroke and myocardial
      infarction. Previously, we reported an appropriate measurement technique of aPLT
      for clinical assay. In this paper, we investigated stable conditions for
      measurement of activating capacity of platelets. METHODS: Blood samples were
      taken from healthy volunteers using anticoagulants of 2K-EDTA, sodium citrate and
      heparin, and platelets were stimulated with adenosine diphosphate (ADP) or
      collagen. We demonstrated platelet-activating capacity by detection of scattering
      light, absorbance, microscopic observation, and P-selectin (CD62P) expression. We
      also performed basic experiments in seven healthy volunteers to test the clinical
      application of these assays with monitoring aspirin therapy. RESULTS: We judged
      that samples of whole blood with 2K-EDTA were suitable for CD62P expression assay
      as functional assessments of platelet activity, because platelets treated with
      anticoagulants such as sodium citrate and heparin were extremely damaged after
      stimulation, and it was difficult to measure the CD62P expression by flow
      cytometry. For optimal results, samples should be tested within 1 h after the
      drawing of blood and stimulated with ADP or collagen for 10 min. The CD62P
      positive platelet value of blood from volunteers who had taken aspirin was
      decreased, and platelet activation was inhibited as well. CONCLUSION: The
      simultaneous assay of aPLT and platelet-activating capacity by CD62P detection
      using whole blood treated with the K2-EDTA anticoagulant was useful for the
      monitoring of antiplatelet drugs.

PMID- 22862793
TI  - Oxidative stress markers are associated to vascular recurrence in non
      cardioembolic stroke patients non-treated with statins.
AB  - BACKGROUND: Since atherogenesis is related to oxidative stress, our objective was
      to study the association of oxidative stress markers with the vascular recurrence
      in non-cardioembolic stroke. METHODS: Atherosclerotic and oxidative stress
      markers were evaluated on admission, in 477 patients suffering from a first non
      cardioembolic stroke. Patients were followed at 6 and 12 months after inclusion,
      recording cardiovascular events. As markers of endothelial oxidative stress we
      used oxidized LDL, Cu/Zn superoxide dismutase and 8-OH deoxiguanosine. 136
      patients were being treated with statins at the moment of serum samples
      acquisition. RESULTS: Patients who suffered vascular recurrence or vascular
      origin death had higher levels of 8-OHDG (40.06 +/- 24.70 vs 33.11 +/-
      15.18;p=0.003). We also found associations between vascular recurrence or
      vascular origin death and Cu/ZnSOD (OR,1.02; 95%CI,1.00-1.03;p=0.0001) and 8-OHDG
      (OR,1.12;95%CI,1.08-1.16;p<0.0001) in a subgroup of 333 patients that were not in
      treatment with statins on admission. We also found associations between 8-OHDG
      and intima media thickness (IMT) (OR,1.13;95%CI,1.09-1.16;p<0.0001), presence of
      ipsilatieral stenosis >= 50% (OR,1.03;95%CI 1.00-1.05;p=0.007) and other
      atherosclerotic plaque characteristics. CONCLUSIONS: Specific oxidative stress
      markers were found to be markers of atherosclerosis plaque types and vascular
      recurrence in non-statins treated patients at admission.

PMID- 22862795
TI  - Joint malaria surveys lead towards improved cross-border cooperation between
      Savannakhet province, Laos and Quang Tri province, Vietnam.
AB  - BACKGROUND: In Savannakhet province, Laos and Quang Tri province, Vietnam,
      malaria is still an important health problem and most cases are found in the
      mountainous, forested border areas where ethnic minority groups live. The
      objectives of this study were to obtain a better joint understanding of the
      malaria situation along the border and, on the basis of that, improve malaria
      control methods through better cooperation between the two countries. METHODS:
      Fourteen villages in Savannakhet and 22 villages in Quang Tri were randomly
      selected within 5 km from the border where a blood survey for microscopic
      diagnosis (n = 1256 and n = 1803, respectively), household interviews (n = 400,
      both sides) and vector surveys were conducted between August and October 2010.
      Satellite images were used to examine the forest density around the study
      villages. RESULTS: Malaria prevalence was significantly higher in Laos (5.2%)
      than in Vietnam (1.8%) and many other differences were found over the short
      distance across the border. Bed net coverage was high (> 90%) in both Laos and
      Vietnam but, while in Laos more than 60% of the nets were long-lasting
      insecticide-treated, Vietnam used indoor residual spraying in this area and the
      nets were untreated. Anopheles mosquitoes were more abundant in Laos than in
      Vietnam, especially many Anopheles dirus were captured in indoor light traps
      while none were collected in Vietnam. The forest cover was higher around the Lao
      than the Vietnamese villages. After this study routine exchange of malaria
      surveillance data was institutionalized and for the first time indoor residual
      spraying was applied in some Lao villages. CONCLUSIONS: The abundance of indoor
      collected An. dirus on the Laos side raises doubts about the effectiveness of a
      sole reliance on long-lasting insecticide-treated nets in this area. Next to
      strengthening the early detection, correct diagnosis and prompt, adequate
      treatment of malaria infections, it is recommended to test focal indoor residual
      spraying and the promotion of insect repellent use in the early evening as
      additional vector interventions. Conducting joint malaria surveys by staff of two
      countries proved to be effective in stimulating better collaboration and improve
      cross-border malaria control.

PMID- 22862796
TI  - Combining structured decision making and value-of-information analyses to
      identify robust management strategies.
AB  - Structured decision making and value-of-information analyses can be used to
      identify robust management strategies even when uncertainty about the response of
      the system to management is high. We used these methods in a case study of
      management of the non-native invasive species gray sallow willow (Salix cinerea)
      in alpine Australia. Establishment of this species is facilitated by wildfire.
      Managers are charged with developing a management strategy despite extensive
      uncertainty regarding the frequency of fires, the willow's demography, and the
      effectiveness of management actions. We worked with managers in Victoria to
      conduct a formal decision analysis. We used a dynamic model to identify the best
      management strategy for a range of budgets. We evaluated the robustness of the
      strategies to uncertainty with value-of-information analyses. Results of the
      value-of-information analysis indicated that reducing uncertainty would not
      change which management strategy was identified as the best unless budgets
      increased substantially. This outcome suggests there would be little value in
      implementing adaptive management for the problem we analyzed. The value-of
      information analyses also highlighted that the main driver of gray sallow willow
      invasion (i.e., fire frequency) is not necessarily the same factor that is most
      important for decision making (i.e., willow seed dispersal distance). Value of
      information analyses enables managers to better target monitoring and research
      efforts toward factors critical to making the decision and to assess the need for
      adaptive management.

PMID- 22862797
TI  - Molecular oxygen reduction electrocatalyzed by meso-substituted cobalt corroles
      coated on edge-plane pyrolytic graphite electrodes in acidic media.
AB  - Five meso-substituted cobalt(III) corroles were examined as to their catalytic
      activity for the electoreduction of O(2) when coated on an edge-plane pyrolytic
      graphite electrode in 1.0 M HClO(4). The investigated compounds are represented
      as (TpRPCor)Co(PPh(3)), where TpRPCor is the trianion of a para-substituted
      triphenylcorrole and R = OMe, Me, H, F, or Cl. Three electrochemical techniques,
      cyclic voltammetry, linear sweep voltammetry with a rotating disk electrode
      (RDE), and voltammetry at a rotating ring disk electrode (RRDE), were utilized to
      evaluate the catalytic activity of the corroles in the reduction of O(2). Cobalt
      corroles containing electron-withdrawing substituents were shown to be better
      catalysts than those having electron-donating groups on the three meso-phenyl
      rings of the triarylcorroles.

PMID- 22862798
TI  - Wavelength-converted/selective waveguiding based on composition-graded
      semiconductor nanowires.
AB  - Compact wavelength-sensitive optical components are desirable for optical
      information processing and communication in photonic integrated system. In this
      work, optical waveguiding along single composition-graded CdS(x)Se(1-x) nanowires
      were systematically investigated. Under a focused laser excitation, the excited
      light can be guided passively along the bandgap-increased direction of the
      nanowire, keeping the photonic energy of the guided light almost unchanged during
      the whole propagation. In comparison, the excited light is guided actively
      through incessantly repeated band-to-band reabsorption and re-emitting processes
      along the bandgap-decreased direction, resulting in a gradual wavelength
      conversion during propagation. On the basis of this wavelength-converted
      waveguiding, a concept of nanoscale wavelength splitter is demonstrated by
      assembling a graded nanowire with several composition-uniform nanowires into
      branched nanowire structure. Our study indicates that composition-graded
      semiconductor nanowires would open new exciting opportunities in developing new
      wavelength-sensitive optical components for integrated nanophotonic devices.

PMID- 22862799
TI  - Prophylactic human papillomavirus vaccination and primary prevention of cervical
      cancer: issues and challenges.
AB  - Two prophylactic human papillomavirus (HPV) vaccines have been recently approved:
      one quadrivalent and the other a bivalent vaccine. When administered in a three
      dose course to HPV-naive individuals, both vaccines exhibited excellent safety
      profiles and were highly efficacious against targeted clinical endpoints in large
      scale international phase III clinical trials. Where coverage has been high for
      the appropriate target population, a reduction of HPV-related diseases with the
      shortest incubation periods has already been seen. By March 2012, universal HPV
      vaccination had been introduced into national vaccination programmes in more than
      40 countries, but only in a few low-income and middle-income countries. With the
      growing market for HPV vaccines and competition between manufacturers, negotiated
      prices are already beginning to decline although they still remain out of reach
      of many countries. The great majority of countries are struggling to reach a
      level of coverage that will have the most impact on cervical cancer rates.
      Increasing coverage and improving completion of the HPV vaccine schedule,
      particularly of sexually naive females, is now the most important public-health
      issue in HPV vaccine efforts. A clear strategy for integrating primary (HPV
      vaccination) and secondary (screening) cervical cancer prevention must be agreed
      as soon as possible. Several second-generation prophylactic vaccines are being
      developed with the aim of resolving some of the limitations of the two current
      HPV prophylactic vaccines.

PMID- 22862800
TI  - Avian influenza virus H5N1 induces rapid interferon-beta production but shows
      more potent inhibition to retinoic acid-inducible gene I expression than H1N1 in
      vitro.
AB  - BACKGROUND: The mechanisms through which the avian influenza virus H5N1 modulate
      the host's innate immune defense during invasion, remains incompletely
      understood. RIG-I as a pattern recognition receptor plays an important role in
      mediating innate immune response induced by influenza virus. So, modulating RIG-I
      might be adopted as a strategy by influenza virus to antagonize the host's innate
      immune defense. METHODS: Here we chose an avian influenza virus A/tree
      sparrow/Henan/1/04 (H5N1) directly isolated from a free-living tree sparrow in
      Mainland China which is amplified in egg allantoic cavity, and researched its
      interferon induction and manipulation of RIG-I expression compared with influenza
      virus A/WSN/1933(H1N1), a well characterized mouse adapted strain, in human lung
      epithelial A549 cells and human embryonic kidney 293T cells. RESULTS: Although
      the avian influenza virus H5N1 infection initiated a rapid IFN-beta production
      early on, it eventually presented a more potent inhibition to IFN-beta production
      than H1N1. Correspondingly, the H5N1 infection induced low level expression of
      endogenous RIG-I, an Interferon Stimulating Gene (ISG), and showed more potent
      inhibition to the expression of endogenous RIG-I triggered by exogenous
      interferon than H1N1. CONCLUSIONS: Manipulating endogenous RIG-I expression might
      constitute one of the mechanisms through which avian influenza virus H5N1 control
      the host's innate immune response during infection.

PMID- 22862801
TI  - Rhizobacteria Bacillus subtilis restricts foliar pathogen entry through stomata.
AB  - Plants exist in a complex multitrophic environment, where they interact with and
      compete for resources with other plants, microbes and animals. Plants have a
      complex array of defense mechanisms, such as the cell wall being covered with a
      waxy cuticle serving as a potent physical barrier. Although some pathogenic fungi
      infect plants by penetrating through the cell wall, many bacterial pathogens
      invade plants primarily through stomata on the leaf surface. Entry of the foliar
      pathogen, Pseudomonas syringae pathovar tomato DC3000 (hereafter PstDC3000), into
      the plant corpus occurs through stomatal openings, and consequently a key plant
      innate immune response is the transient closure of stomata, which delays disease
      progression. Here, we present evidence that the root colonization of the
      rhizobacteria Bacillus subtilis FB17 (hereafter FB17) restricts the stomata
      mediated pathogen entry of PstDC3000 in Arabidopsis thaliana. Root binding of
      FB17 invokes abscisic acid (ABA) and salicylic acid (SA) signaling pathways to
      close light-adapted stomata. These results emphasize the importance of
      rhizospheric processes and environmental conditions as an integral part of the
      plant innate immune system against foliar bacterial infections.

PMID- 22862803
TI  - Ganglion cysts of the cruciate ligaments: a series of 31 cases and review of the
      literature.
AB  - BACKGROUND: A case series for ganglion cyst of the cruciate ligament with MRI
      findings, clinical presentation, and management options along with review of
      literature is presented. METHODS: Of 8663 consecutive patients referred for knee
      MR imaging, 31 were diagnosed with ganglion cysts of the cruciate ligaments,
      including 21 men and 10 women of ages 12 to 73 years (mean: 37). A review of
      charts revealed that knee pain was the chief complaint in all cases. Arthroscopic
      debridement of ganglion cyst was performed in 11 patients. RESULTS: MRI proved to
      be a valuable tool in diagnosing and deciding management of these cases. All 11
      patients who underwent arthroscopic treatment were symptom-free on a minimum
      follow-of one year. CONCLUSION: Cyst formation associated with cruciate ligament
      of the knee is an infrequent cause of knee pain. MR imaging was important in
      confirming the cyst lesions and provided useful information prior to arthroscopy.
      Arthroscopic debridement of ganglion cyst produced excellent outcome without
      recurrence. This study describes the pertinent MRI and intraoperative findings of
      ganglion cyst.

PMID- 22862802
TI  - Conditioned mesenchymal stem cells attenuate progression of chronic kidney
      disease through inhibition of epithelial-to-mesenchymal transition and immune
      modulation.
AB  - Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute
      renal injury models; but whether MSCs can delay renal failure in chronic kidney
      disease (CKD) remains unclear. In the present study, the were cultured in media
      containing various concentrations of basic fibroblast growth factor, epidermal
      growth factor and ascorbic acid 2-phosphate to investigate whether hepatocyte
      growth factor (HGF) secretion could be increased by the stimulation of these
      growth factors. Then, TGF-beta1-treated renal interstitial fibroblast (NRK-49F),
      renal proximal tubular cells (NRK-52E) and podocytes were co-cultured with
      conditioned MSCs in the absence or presence of ascorbic acid 2-phosphate to
      quantify the protective effects of conditioned MSCs on renal cells. Moreover,
      male Sprague-Dawley rats were treated with 1 * 10(6) conditioned MSCs immediately
      after 5/6 nephrectomy and every other week through the tail vein for 14 weeks. It
      was found that basic fibroblast growth factor, epidermal growth factor and
      ascorbic acid 2-phosphate promoted HGF secretion in MSCs. Besides, conditioned
      MSCs were found to be protective against TGF-beta1 induced epithelial-to
      mesenchymal transition of NRK-52E and activation of NRK-49F cells. Furthermore,
      conditioned MSCs protected podocytes from TGF-beta1-induced loss of synaptopodin,
      fibronectin induction, cell death and apoptosis. Rats transplanted with
      conditioned human MSCs had a significantly increase in creatinine clearance rate,
      decrease in glomerulosclerosis, interstitial fibrosis and increase in
      CD4(+)CD25(+)Foxp3(+) regulatory T cells counts in splenocytes. Together, our
      studies indicated that conditioned MSCs preserve renal function by their anti
      fibrotic and anti-inflammatory effects. Transplantation of conditioned MSCs may
      be useful in treating CKD.

PMID- 22862804
TI  - The "Suicide Guard Rail": a minimal structural intervention in hospitals reduces
      suicide jumps.
AB  - BACKGROUND: Jumping from heights is a readily available and lethal method of
      suicide. This study examined the effectiveness of a minimal structural
      intervention in preventing suicide jumps at a Swiss general teaching hospital.
      Following a series of suicide jumps out of the hospital's windows, a metal guard
      rail was installed at each window of the high-rise building. RESULTS: In the 114
      months prior to the installation of the metal guard rail, 10 suicides by jumping
      out of the hospital's windows occurred among 119,269 inpatients. This figure was
      significantly reduced to 2 fatal incidents among 104,435 inpatients treated
      during the 78 months immediately following the installation of the rails at the
      hospital's windows (chi2 = 4.34, df = 1, p = .037). CONCLUSIONS: Even a minimal
      structural intervention might prevent suicide jumps in a general hospital.
      Further work is needed to examine the effectiveness of minimal structural
      interventions in preventing suicide jumps.

PMID- 22862805
TI  - Utility of nuclear stress imaging for detecting coronary artery bypass graft
      disease.
AB  - BACKGROUND: The value of single photon emission computed tomography stress
      myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after
      coronary artery bypass surgery (CABG) has not been studied prospectively in an
      unselected cohort. METHODS: Radial Artery Versus Saphenous Vein Graft Study is a
      Veterans Affairs Cooperative Study to determine graft patency rates after CABG
      surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their
      coronary angiogram, one-year after CABG. The choice of the stress protocol was
      made at the discretion of the nuclear radiologist and was either a symptom
      limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI
      results were interpreted independent of the angiographic results and estimates of
      sensitivity, specificity and accuracy were based on the prediction of a graft
      stenosis of >=70% on coronary angiogram. RESULTS: A significant stenosis was
      present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress
      tests with an optimal exercise heart rate response (>80% maximum predicted heart
      rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting
      the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it
      was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise
      heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis
      was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary
      significantly with ischemic territory. CONCLUSIONS: Under optimal stress
      conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft
      disease in an unselected patient population 1 year post-CABG.

PMID- 22862806
TI  - Effects of cinnamon (Cinnamomum zeylanicum) bark oil on testicular antioxidant
      values, apoptotic germ cell and sperm quality.
AB  - Cinnamon and its contents have multifactorial properties such as antioxidant,
      anti-inflammatory and antidiabetic. Male infertility is one of the major health
      problems in life. The aim of this study was to investigate the effects of long
      term cinnamon bark oil (CBO) ingestion on testicular antioxidant values,
      apoptotic germ cell and sperm quality of adult rats. Twelve male healthy Wistar
      rats were divided into two groups, each group containing six rats. While olive
      oil was given to control group, 100 mg kg(-1)  CBO was administered to the other
      group by gavage daily for 10 weeks. Body and reproductive organ weights, sperm
      characteristics, testicular lipid peroxidation and antioxidant enzyme activities,
      and testicular apoptosis via terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labelling (TUNEL) method were examined. A significant decrease in
      malondialdehyde level and marked increases in reduced glutathione level,
      glutathione peroxidase and catalase activities were observed in rats treated with
      CBO compared with the control group. CBO consumption provided a significant
      increase in weights of testes and epididymides, epididymal sperm concentration,
      sperm motility and diameter of seminiferous tubules when compared with the
      control group. However, CBO consumption tended to decrease the abnormal sperm
      rate and apoptotic germ cell count, but it did not reach statistical
      significance. It is concluded that CBO has improvement effect on testicular
      oxidant-antioxidant balance and sperm quality, and its consumption may be useful
      for asthenozoospermic men. 

PMID- 22862807
TI  - A case-control study of risk factors for bovine cysticercosis in Danish cattle
      herds.
AB  - Bovine cysticercosis (BC) is a zoonotic, parasitic infection in cattle. Under the
      current EU meat inspection regulation, every single carcass from all bovines
      above 6 weeks of age is examined for BC. This method is costly and makes more
      sense in countries with higher number of BC-infected animals than in countries
      with few lightly infected cases per year. The aim of the present case-control
      study was to quantify associations between potential herd-level risk factors and
      BC in Danish cattle herds. Risk factors can be used in the design of a risk-based
      meat inspection system targeted towards the animals with the highest risk of BC.
      Cases (n = 77) included herds that hosted at least one animal diagnosed with BC
      at meat inspection, from 2006 to 2010. Control herds (n = 231) consisted of
      randomly selected herds that had not hosted any animals diagnosed with BC between
      2004 and 2010. The answers from a questionnaire and register data from the Danish
      Cattle Database were grouped into meaningful variables and used to investigate
      the risk factors for BC using a multivariable logistic regression model. Case
      herds were almost three times more likely than control herds to let all or most
      animals out grazing. Case herds were more than five times more likely than
      control herds to allow their animals access to risky water sources with sewage
      treatment plant effluent in proximity. Case herds were also more likely to share
      machinery or hire contractors than control herds. The risk decreased with
      increasing herd size probably because the larger herds generally tend to keep
      cattle indoors in Denmark. The results are useful to guide future data recording
      that can be supplied by the farmer as food chain information and then be used for
      differentiated meat inspection in low- and high-risk groups, enabling development
      of risk-based meat inspection systems.

PMID- 22862808
TI  - The anti-biofilm activity of lemongrass (Cymbopogon flexuosus) and grapefruit
      (Citrus paradisi) essential oils against five strains of Staphylococcus aureus.
AB  - AIMS: To determine the sensitivity of five strains of Staphylococcus aureus to
      five essential oils (EOs) and to investigate the anti-biofilm activity of
      lemongrass and grapefruit EOs. METHODS AND RESULTS: Antimicrobial susceptibility
      screening was carried out using the disk diffusion method. All of the strains
      tested were susceptible to lemongrass, grapefruit, bergamot and lime EOs with
      zones of inhibition varying from 2.85 to 8.60 cm although they were resistant to
      lemon EO. Lemongrass EO inhibited biofilm formation at 0.125% (v/v) as measured
      by colorimetric assay and at 0.25% (v/v) no metabolic activity was observed as
      determined by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
      carboxanilide (XTT) reduction. Grapefruit EO did not show any anti-biofilm
      activity. Following exposure to lemongrass EO extensive disruption to Staph.
      aureus biofilms was shown under scanning electron microscopy. CONCLUSIONS: In
      comparison to the other EOs tested, lemongrass exhibited the most effective
      antimicrobial and anti-biofilm activity. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The effect of lemongrass EO highlights its potential against antibiotic resistant
      Staph. aureus in the healthcare environment.

PMID- 22862809
TI  - Abstracts of the World Meeting on Sexual Medicine. Chicago, Illinois, USA. August
      26-30, 2012.

PMID- 22862810
TI  - First nosocomial outbreak of VIM-16-producing Serratia marcescens in Argentina.
AB  - Seven metallo-beta-lactamase-positive isolates of Serratia marcescens were
      recovered from three patients hospitalized in a neonatal ward in an Argentinean
      hospital during the period July-September 2011. All the isolates were multidrug
      resistant, they belonged to a single clone, and carried a blaVIM-16 -containing
      class I integron structure. This represents the first nosocomial outbreak of
      metallo-beta-lactamase in Enterobacteriaceae in Argentina.

PMID- 22862811
TI  - Associations of health, physical activity and weight status with motorised travel
      and transport carbon dioxide emissions: a cross-sectional, observational study.
AB  - BACKGROUND: Motorised travel and associated carbon dioxide (CO2) emissions
      generate substantial health costs; in the case of motorised travel, this may
      include contributing to rising obesity levels. Obesity has in turn been
      hypothesised to increase motorised travel and/or CO2 emissions, both because
      heavier people may use motorised travel more and because heavier people may
      choose larger and less fuel-efficient cars. These hypothesised associations have
      not been examined empirically, however, nor has previous research examined
      associations with other health characteristics. Our aim was therefore to examine
      how and why weight status, health, and physical activity are associated with
      transport CO2 emissions. METHODS: 3463 adults completed questionnaires in the
      baseline iConnect survey at three study sites in the UK, reporting their health,
      weight, height and past-week physical activity. Seven-day recall instruments were
      used to assess travel behaviour and, together with data on car characteristics,
      were used to estimate CO2 emissions. We used path analysis to examine the extent
      to which active travel, motorised travel and car engine size explained
      associations between health characteristics and CO2 emissions. RESULTS: CO2
      emissions were higher in overweight or obese participants (multivariable
      standardized probit coefficients 0.16, 95% CI 0.08 to 0.25 for overweight vs.
      normal weight; 0.16, 95% CI 0.04 to 0.28 for obese vs. normal weight). Lower
      active travel and, particularly for obesity, larger car engine size explained 19
      31% of this effect, but most of the effect was directly explained by greater
      distance travelled by motor vehicles. Walking for recreation and leisure-time
      physical activity were associated with higher motorised travel distance and
      therefore higher CO2 emissions, while active travel was associated with lower CO2
      emissions. Poor health and illness were not independently associated with CO2
      emissions. CONCLUSIONS: Establishing the direction of causality between weight
      status and travel behaviour requires longitudinal data, but the association with
      engine size suggests that there may be at least some causal effect of obesity on
      CO2 emissions. More generally, transport CO2 emissions are associated in
      different ways with different health-related characteristics. These include
      associations between health goods and environmental harms (recreational physical
      activity and high emissions), indicating that environment-health 'co-benefits'
      cannot be assumed. Instead, attention should also be paid to identifying and
      mitigating potential areas of tension, for example by promoting low-carbon
      recreational physical activity.

PMID- 22862812
TI  - Prospects for three-electron donor boronyl (BO) ligands and dioxodiborene (B2O2)
      ligands as bridging groups in binuclear iron carbonyl derivatives.
AB  - Recent experimental work (2010) on (Cy(3)P)(2)Pt(BO)Br indicates that the oxygen
      atom of the boronyl (BO) ligand is more basic than that in the ubiquitous CO
      ligand. This suggests that bridging BO ligands in unsaturated binuclear metal
      carbonyl derivatives should readily function as three-electron donor bridging
      ligands involving both the oxygen and the boron atoms. In this connection,
      density functional theory shows that three of the four lowest energy singlet
      Fe(2)(BO)(2)(CO)(7) structures have such a bridging eta(2)-MU-BO group as well as
      a formal Fe-Fe single bond. In addition, all four of the lowest energy singlet
      Fe(2)(BO)(2)(CO)(6) structures have two bridging eta(2)-MU-BO groups and formal
      Fe-Fe single bonds. Other Fe(2)(BO)(2)(CO)(n) (n = 7, 6) structures are found in
      which the two BO groups have coupled to form a bridging dioxodiborene (B(2)O(2))
      ligand with B-B bonding distances of ~1.84 A. All of these Fe(2)(MU
      B(2)O(2))(CO)(n) structures have long Fe...Fe distances indicating a lack of
      direct iron-iron bonding. One of the singlet Fe(2)(BO)(2)(CO)(7) structures has
      such a bridging dioxodiborene ligand with cis stereochemistry functioning as a
      six-electron donor to the pair of iron atoms. In addition, the lowest energy
      triplet structures for both Fe(2)(BO)(2)(CO)(7) and Fe(2)(BO)(2)(CO)(6) have
      bridging dioxodiborene ligands with trans stereochemistry functioning as a four
      electron donor to the pair of iron atoms.

PMID- 22862813
TI  - Integrated circuits based on bilayer MoS2 transistors.
AB  - Two-dimensional (2D) materials, such as molybdenum disulfide (MoS(2)), have been
      shown to exhibit excellent electrical and optical properties. The semiconducting
      nature of MoS(2) allows it to overcome the shortcomings of zero-bandgap graphene,
      while still sharing many of graphene's advantages for electronic and
      optoelectronic applications. Discrete electronic and optoelectronic components,
      such as field-effect transistors, sensors, and photodetectors made from few-layer
      MoS(2) show promising performance as potential substitute of Si in conventional
      electronics and of organic and amorphous Si semiconductors in ubiquitous systems
      and display applications. An important next step is the fabrication of fully
      integrated multistage circuits and logic building blocks on MoS(2) to demonstrate
      its capability for complex digital logic and high-frequency ac applications. This
      paper demonstrates an inverter, a NAND gate, a static random access memory, and a
      five-stage ring oscillator based on a direct-coupled transistor logic technology.
      The circuits comprise between 2 to 12 transistors seamlessly integrated side-by
      side on a single sheet of bilayer MoS(2). Both enhancement-mode and depletion
      mode transistors were fabricated thanks to the use of gate metals with different
      work functions.

PMID- 22862814
TI  - Two novel mutations in the 3' untranslated region of the beta-globin gene that
      are associated with the mild phenotype of beta thalassemia.
AB  - INTRODUCTION: There are approximately 800 different genomic alterations of the
      beta-globin gene described in the human hemoglobin variant (HbVar) database. In
      this study, we have identified two novel putative mutations (HBB:c.*+108 A>G and
      HBB:c.*+132 C>T) in the 3' untranslated region (3'-UTR) of the beta-globin gene
      and describe their clinical implications. METHODS: Four patients from two
      unrelated families, all with hematological and clinical features associated with
      beta-thalassemia (beta-thal), and their family members were included. The
      molecular diagnoses of the beta-globin gene mutations were performed by direct
      sequencing. RESULTS: A novel mutation, HBB:c.*+108 A>G, was found in combination
      with the IVS-I-110 G>A (HBB:c.93-21 G>A) mutation in three siblings (two brothers
      and one sister) from one of the families involved in our study. Their mother was
      found to be a carrier for HBB:c.*+108 A>G with normal HbA2 levels. The other
      novel mutation, HBB:c.*+132 C>T, was found in combination with IVS-I-1 G>A
      (HBB:c.92 + 1G>A) in a 7-year-old boy diagnosed as beta-thal intermedia from the
      second family. His father and two brothers were all carriers of HBB:c.*+132 C>T
      with borderline HbA2 levels. CONCLUSION: Based on the observed beta-thal
      intermedia phenotypes and the accompanying mutations, we conclude that these
      novel beta-globin gene 3' UTR mutations are associated with the mild phenotype of
      beta-thal.

PMID- 22862815
TI  - 30 years on: what can HIV treatment do for HIV prevention?
AB  - This article looks at the progress that has been made in understanding
      transmission, treatment and prevention of human immunodeficiency virus (HIV) and
      acquired immunodeficiency syndrome (AIDS) since its first recognized appearance
      in 1981. Drawing on epidemiological data, it shows that despite our understanding
      of the infection, its transmission, and ways in which it can be managed, it
      remains a significant and growing challenge in both biological and population
      terms. With recent reports estimating that the cost of therapy is L 1 billion per
      annum in the UK, this paper identifies and reflects on some of the emerging
      opportunities and challenges for HIV treatment and prevention.

PMID- 22862816
TI  - Assessment of pharmacological strategies for management of major depressive
      disorder and their costs after an inadequate response to first-line
      antidepressant treatment in primary care.
AB  - BACKGROUND: The aim of the study was to determine the most common treatment
      strategies and their costs for patients with an inadequate response to first-line
      antidepressant treatment (AD) in primary care. METHOD: A retrospective cohort
      study of medical records from six primary care centers was conducted. Adults with
      a major depressive disorder diagnosis, at least 8 weeks of AD treatment after the
      first prescription, and patient monitoring for 12 months were analyzed.
      Healthcare (direct cost) and non-healthcare costs (indirect costs; work
      productivity losses) were described. RESULTS: A total of 2,260 patients were
      studied. Forty-three percent of patients (N = 965) presented an inadequate
      response to treatment. Summarizing the different treatment approaches: 43.2% were
      switched to another AD, 15.5% were given an additional AD, AD dose was increased
      in 14.6%, and 26.7% remained with the same antidepressant agent.
      Healthcare/annual costs were 451.2 Euros for patients in remission vs. 826.1
      Euros in those with inadequate response, and productivity losses were 991.4
      versus 1,842.0 Euros, respectively (p < 0.001). CONCLUSION: Antidepressant switch
      was the most common therapeutic approach performed by general practitioners in
      naturalistic practice. A delay in treatment change when no remission occurs and a
      significant heterogeneity in management of these patients were also found.

PMID- 22862817
TI  - Intraocular pressure vs intracranial pressure in disease conditions: a
      prospective cohort study (Beijing iCOP study).
AB  - BACKGROUND: The correlation between intracranial pressure (ICP) and intraocular
      pressure (IOP) is still controversial in literature and hence whether IOP can be
      used as a non-invasive surrogate of ICP remains unknown. The aim of the current
      study was to further clarify the potential correlation between ICP and IOP.
      METHODS: The IOP measured with Goldmann applanation tonometer was carried out on
      130 patients whose ICP was determined via lumber puncture. The Pearson
      correlation coefficient between ICP and IOP was calculated, the fisher line
      discriminated analysis to evaluate the effectivity of using IOP to predict the
      ICP level. RESULTS: A significant correlation between ICP and IOP was found. ICP
      was correlated significantly with IOP of the right eyes (p < 0.001) and IOP of
      the left eyes (p = 0.001) and mean IOP of both eyes (p < 0.001), respectively.
      However, using IOP as a measurement to predict ICP, the accuracy rate was found
      to be 65.4%. CONCLUSION: Our data suggested that although a significant
      correlation exists between ICP and IOP, caution needs to be taken when using IOP
      readings by Goldmann applanation tonometer as a surrogate for direct
      cerebrospinal fluid pressure measurement of ICP.

PMID- 22862818
TI  - Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of
      mechanical load variation.
AB  - Cardiac transverse (t)-tubules are altered during disease and may be regulated by
      stretch-sensitive molecules. The relationship between variations in the degree
      and duration of load and t-tubule structure remains unknown, as well as its
      implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were
      studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic
      abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure
      overloading using thoracic aortic constriction. CICR, cell and t-tubule structure
      were assessed using confocal-microscopy, patch-clamping and scanning ion
      conductance microscopy. Moderate unloading was compared with severe unloading
      [using heart-only transplantation (HAHT)]. Mechanical unloading reduced
      cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was
      reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency
      and duration at 8 weeks of moderate unloading, which also induced t-tubule
      disorganization. Overloading increased cardiomyocyte volume and disrupted t
      tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for
      4 weeks had milder effects compared with severe mechanical unloading (37%
      reduction in cell volume at 4 weeks compared to 56% reduction after severe
      mechanical unloading) and did not cause depression and delay of the Ca(2+)
      transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface
      structure. These data suggest that variations in chronic mechanical load
      influence local CICR and t-tubule structure in a time- and degree-dependent
      manner, and that physiological states of increased and reduced cell size, without
      pathological changes are possible.

PMID- 22862819
TI  - Biogenesis of protein bodies during vicilin accumulation in Medicago truncatula
      immature seeds.
AB  - BACKGROUND: Grain legumes play a worldwide role as a source of plant proteins for
      feed and food. In the model legume Medicago truncatula, the organisation of
      protein storage vacuoles (PSV) in maturing seeds remains unknown. FINDINGS: The
      sub-cellular events accompanying the accumulation of vicilin (globulin7S) were
      analysed during seed mid-maturation. Immuno-detection of vicilin in light
      microscopy, allowed a semi-quantitative assessment of the protein body
      complement. The identified populations of vicilin-containing protein bodies are
      distinguished by their number and size which allowed to propose a model of their
      biogenesis. Two distributions were detected, enabling a separation of their
      processing at early and mid maturation stages. The largest protein bodies, at 16
      and 20  days after pollination (DAP), were formed by the fusion of small bodies.
      They have probably attained their final size and correspond to mature vicilin
      aggregations. Electron microscopic observations revealed the association of the
      dense protein bodies with rough endoplasmic reticulum. The presence of a ribosome
      layer surrounding protein bodies, would support an endoplasmic reticulum-vacuole
      trafficking pathway. CONCLUSIONS: The stastistic analysis may be useful for
      screening mutations of candidate genes governing protein content. The definitive
      evidence for an ER-storage vacuole pathway corresponds to a challenge, for the
      storage of post-translationally unstable proteins. It was proposed for the
      accumulation of one class of storage protein, the vicilins. This alternative
      pathway is a matter of controversy in dicotyledonous seeds.

PMID- 22862820
TI  - Characterization of purified and xerogel immobilized novel lignin peroxidase
      produced from Trametes versicolor IBL-04 using solid state medium of corncobs.
AB  - BACKGROUND: Cost-effective production of industrially important enzymes is a key
      for their successful exploitation on industrial scale. Keeping in view the
      extensive industrial applications of lignin peroxidase (LiP), this study was
      performed to purify and characterize the LiP from an indigenous strain of
      Trametes versicolor IBL-04. Xerogel matrix enzyme immobilization technique was
      applied to improve the kinetic and thermo-stability characteristics of LiP to
      fulfil the requirements of the modern enzyme consumer sector of biotechnology.
      RESULTS: A novel LiP was isolated from an indigenous T. versicolor IBL-04 strain.
      T. versicolor IBL-04 was cultured in solid state fermentation (SSF) medium of
      corn cobs and maximum LiP activity of 592 +/- 6 U/mL was recorded after five days
      of incubation under optimum culture conditions. The crude LiP was 3.3-fold
      purified with specific activity of 553 U/mg after passing through the DEAE
      cellulose and Sephadex-G-100 chromatography columns. The purified LiP exhibited a
      relatively low molecular weight (30 kDa) homogenous single band on native and SDS
      PAGE. The LiP was immobilized by entrapping in xerogel matrix of trimethoxysilane
      (TMOS) and proplytetramethoxysilane (PTMS) and maximum immobilization efficiency
      of 88.6% was achieved. The free and immobilized LiPs were characterized and the
      results showed that the free and immobilized LiPs had optimum pH 6 and 5 while
      optimum temperatures were 60 degrees C and 80 degrees C, respectively.
      Immobilization was found to enhance the activity and thermo-stability potential
      of LiP significantly and immobilized LiP remained stable over broad pH and
      temperature range as compare to free enzyme. Kinetic constants K(m) and V(max)
      were 70 and 56 MUM and 588 and 417 U/mg for the free and immobilized LiPs,
      respectively. Activity of this novel extra thermo-stable LiP was stimulated to
      variable extents by Cu(2+), Mn(2+) and Fe(2+) whereas, Cystein, EDTA and Ag(+)
      showed inhibitory effects. CONCLUSIONS: The indigenously isolated white rot
      fungal strain T. versicolor IBL-04 showed tremendous potential for LiP synthesis
      in SSF of corncobs in high titters (592 U/mL) than other reported Trametes
      (Coriolus, Polyporus) species. The results obtained after dual phase
      characterization suggested xerogel matrix entrapment a promising tool for enzyme
      immobilization, hyper-activation and stabilization against high temperature and
      inactivating agents. The pH and temperature optima, extra thermo-stability
      features and kinetic characteristics of this novel LiP of T. versicolor IBL-04
      make it a versatile enzyme for various industrial and biotechnological
      applications.

PMID- 22862821
TI  - The critical incident inventory: characteristics of incidents which affect
      emergency medical technicians and paramedics.
AB  - BACKGROUND: Emergency medical technicians (EMTs) and paramedics experience
      critical incidents which evoke distress and impaired functioning but it is
      unknown which aspects of incidents contribute to their impact. We sought to
      determine these specific characteristics by developing an inventory of critical
      incident characteristics and testing their relationship to protracted recovery
      from acute stress, and subsequent emotional symptoms. METHODS: EMT/paramedics (n
      = 223) completed a retrospective survey of reactions to an index critical
      incident, and current depressive, posttraumatic and burnout symptoms. Thirty-six
      potential event characteristics were evaluated; 22 were associated with
      peritraumatic distress and were retained. We assigned inventory items to one of
      three domains: situational, systemic or personal characteristics. We tested the
      relationships between (a) endorsing any domain item and (b) outcomes of the
      critical incident (peritraumatic dissociation, recovery from components of the
      Acute Stress Reaction and depressive, posttraumatic, and burnout symptoms).
      Analyses were repeated for the number of items endorsed. RESULTS: Personal and
      situational characteristics were most frequently endorsed. The personal domain
      had the strongest associations, particularly with peritraumatic dissociation,
      prolonged distressing feelings, and current posttraumatic symptoms. The
      situational domain was associated with peritraumatic dissociation, prolonged
      social withdrawal, and current posttraumatic symptoms. The systemic domain was
      associated with peritraumatic dissociation and prolonged irritability. Endorsing
      multiple characteristics was related to peritraumatic, acute stress, and current
      posttraumatic symptoms. Relationships with outcome variables were as strong for a
      14-item inventory (situational and personal characteristics only) as the 22-item
      inventory. CONCLUSIONS: Emotional sequelae are associated most strongly with
      EMT/paramedics' personal experience, and least with systemic characteristics. A14
      item inventory identifies critical incident characteristics associated with
      emotional sequelae. This may be helpful in tailoring recovery support to
      individual provider needs.

PMID- 22862822
TI  - The interaction of amylin with other hormones in the control of eating.
AB  - Twenty years of research established amylin as an important control of energy
      homeostasis. Amylin controls nutrient and energy fluxes by reducing energy
      intake, by modulating nutrient utilization via an inhibition of postprandial
      glucagon secretion and by increasing energy disposal via a prevention of
      compensatory decreases of energy expenditure in weight reduced individuals. Like
      many other gastrointestinal hormones, amylin is secreted in response to meals and
      it reduces eating by promoting meal-ending satiation. Not surprisingly, amylin
      interacts with many of these hormones to control eating. These interactions seem
      to occur at different levels because amylin seems to mediate the eating
      inhibitory effect of some of these gastrointestinal hormones, and the combination
      of some of these hormones seems to lead to a stronger reduction in eating than
      single hormones alone. Amylin's effect on eating is thought to be mediated by a
      stimulation of specific amylin receptors in the area postrema. Secondary brain
      sites that were defined to mediate amylin action - and hence potential additional
      sites of interaction with other hormones - include the nucleus of the solitary
      tract, the lateral parabrachial nucleus, the lateral hypothalamic area and other
      hypothalamic nuclei. The focus of this review is to summarize the current
      knowledge of amylin interactions in the control of eating. In most cases, these
      interactions have only been studied at a descriptive rather than a mechanistic
      level and despite the clear knowledge on primary sites of amylin action, the
      interaction sites between amylin and other hormones are often unknown.

PMID- 22862823
TI  - Association of GATA4 sequence variation with alcohol dependence.
AB  - To further explore reports of association of alcohol dependence and response to
      acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism
      (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol-dependent cases
      and 1248 controls. We tested for association of alcohol dependence with the 11
      SNPs individually and performed a global test for association using a principle
      components analysis. Our analyses demonstrate significant association between
      GATA4 and alcohol dependence at the gene level (P = 0.009) but no association
      with rs13273672. Further studies are needed to identify potential causal GATA4
      variation(s) and the functional mechanism(s) contributing to this association. 

PMID- 22862824
TI  - Joint modeling of success and treatment discontinuation in in vitro fertilization
      programs: a retrospective cohort study.
AB  - BACKGROUND: As discontinuation in in vitro fertilization (IVF) programs has been
      associated with a poor prognosis, one hypothesis is that some couple-specific
      predictive factors in IVF may be shared with opposite effect by both success
      (i.e. live birth) and treatment discontinuation processes. Our objective was to
      perform a joint analysis of these two processes to examine the hypothesis of a
      link between the two processes. METHODS: Analyses were conducted on a
      retrospective cohort of 3,002 women who began IVF between 1998 and 2002 in two
      French IVF centers: a Parisian center and a center in a medium-sized city in
      central France. A shared random effects model based on a joint modelization of
      IVF treatment success and discontinuation was used to study the link between the
      two processes. RESULTS: Success and discontinuation processes were significantly
      linked in the medium-sized city center, whereas they were not linked in the
      Parisian center. The center influenced risk of treatment discontinuation but not
      chance of success. The well-known inverse-J relation between the woman's age and
      chance of success was observed, as expected. Risk of discontinuation globally
      increased as the woman's age increased. CONCLUSIONS: The link between success and
      discontinuation processes could depend on the fertility center. In particular,
      the woman's decision to pursue or to discontinue IVF in a particular center could
      depend on the presence of other IVF centers in the surrounding area.

PMID- 22862825
TI  - A multivariate twin study of female sexual dysfunction.
AB  - INTRODUCTION: There is little work on the etiology of female sexual dysfunction
      (FSD), a highly contentious and heterogeneous disorder from classification and
      clinical perspectives. Clarifying causative mechanisms may enhance current
      psychiatric nosology. AIM: To elucidate the structure of genetic and
      environmental risk factors underlying the major subtypes of FSD. METHODS: Self
      report questionnaires and multivariate twin model fitting on a population-based
      adult twin register (TwinsUK, London) including 1,489 female twins aged 18 to 85,
      comprising 244 MZ pairs, 189 DZ pairs, and 623 women whose co-twins did not
      participate. MAIN OUTCOME MEASURES: Scores on the Female Sexual Function Index
      Lifelong and its six dimensions (desire, arousal, lubrication, orgasm,
      satisfaction, and pain) were subject to univariate and multivariate variance
      component analysis. RESULTS: The best-fitting multivariate model was an ACE
      Cholesky model, in which both additive genetic effects and non-shared
      environmental effects loaded on four FSD dimensions. There was significant
      genetic sharing between desire, arousal, lubrication and orgasm, but there was
      also significant genetic sharing between arousal, lubrication and orgasm
      independent of desire. These genetic loadings were small to modest effects (7% to
      33%). Bivariate heritabilities suggested that a third of the covariance between
      these dimensions was genetic. Desire shared the least amount of genetic
      association with lubrication and orgasm. Non-shared environmental effects (which
      were stronger than genetic effects) were somewhat more dimension-specific.
      CONCLUSIONS: FSD is not etiologically homogeneous. There are at least two genetic
      factors to FSD symptomatology, and a tendency for more dimension-specific non
      shared environmental factors as a more important indicative of unique factors
      involved in specific types of sexual problems reported by women. These results
      emphasize genetic factors as possible organizing principles for an etiologically
      based classification approach of FSD.

PMID- 22862826
TI  - The prevalence, distribution and characterization of Shiga toxin-producing
      Escherichia coli (STEC) serotypes and virulotypes from a cluster of bovine farms.
AB  - AIMS: To assess the prevalence of Shiga toxin-producing Escherichia coli (STEC)
      on a cluster of twelve beef farms in the north-east of Ireland. METHODS AND
      RESULTS: Samples were screened for stx1 and stx2 using PCR. Positive samples were
      enriched in mTSB and STEC O157 isolated using immunomagnetic separation.
      Enrichment cultures were plated onto TBX agar to isolate non-O157 STEC. All
      isolates were serotyped and examined for a range of virulence genes and their
      antibiotic resistance phenotype determined. Eighty-four isolates of 33 different
      serotypes were cultured from the 13.7% of samples that were stx positive. The
      most prevalent serotype was O157:H7, the most common Shiga toxin was stx(2) , and
      a variety of virulence factor combinations was observed. O-:H-, O26:H11, O76:H34,
      O157:H7, O157:H16 and OX18:H+ also carried eaeA and hlyA genes. Twenty-nine per
      cent of strains were resistant to at least one antibiotic, 48% of which had
      multiple drug resistance (MDR) with O2:H32 displaying resistance to five
      antibiotics. CONCLUSIONS: The ubiquitous nature of STEC on beef farms, the
      detection of stx(+)  eaeA(+)  hlyA(+)  in the serotypes O-:H-, O157:H16 and
      OX18:H+ in addition to O157:H7 and O26:H11 and the widespread distribution of
      antibiotic resistance are of public health concern as new virulent STEC strains
      are emerging. SIGNIFICANCE AND IMPACT OF THE STUDY: This study found no
      relationship between serotype and antibiotic resistance, therefore negating
      efforts to isolate serotypes using specific antibiotic supplemented media. The
      data presented provide further evidence of the emergence of new STEC virulotypes
      of potential public health significance.

PMID- 22862827
TI  - Aprepitant versus ondansetron in preoperative triple-therapy treatment of nausea
      and vomiting in neurosurgery patients: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: The incidence of postoperative nausea and vomiting (PONV) is 50% to
      80% after neurosurgery. The common prophylactic treatment for postoperative
      nausea and vomiting is a triple therapy of droperidol, promethazine and
      dexamethasone. Newer, more effectives methods of prophylaxis are being
      investigated. We designed this prospective, double-blind, single-center study to
      compare the efficacy of ondansetron, a neurokinin-1 antagonist, and aprepitant,
      as a substitute for droperidol, in the prophylactic treatment of postoperative
      nausea and vomiting after neurosurgery. METHODS: After obtaining institutional
      review board approval; 176 patients, 18 to 85 years of age with American Society
      of Anesthesiologists (ASA) classifications I to III, who did not receive
      antiemetics 24 h before surgery and were expected to undergo general anesthesia
      for neurosurgery lasting longer than 2 h were included in this study. After
      meeting the inclusion and exclusion criteria and providing written informed
      consent, patients were randomly assigned in a 1:1 ratio to one of two treatment
      groups: aprepitant or ondansetron. The objective of this study was to conduct a
      randomized, double-blind, double-dummy, parallel-group and single-center trial to
      compare and evaluate the efficacies of aprepitant versus ondansetron. Patients
      received oral aprepitant 40 mg OR oral dummy pill within 2 h prior to induction.
      At induction, a combination of intravenous dexamethasone 10 mg, promethazine 25
      mg, and ondansetron 4 mg OR dummy injection was administered. Therefore, all
      patients received one dummy treatment and three active PONV prophylactic
      medications: dexamethasone 10 mg, promethazine 25 mg, and either aprepitant 40 mg
      OR ondansetron 4 mg infusion. The primary outcome measures were the episodes and
      severity of nausea and vomiting; administration of rescue antiemetic; and opioid
      consumption for 120 h postoperatively. Standard safety assessments included
      adverse event reports, physical and laboratory data, awakening time and duration
      of recovery from anesthesia. DISCUSSION: The results of this comparative study
      could potentially identify an improved treatment regimen that may decrease the
      incidence and severity of postoperative nausea and vomiting in patients
      undergoing neurosurgery. Also, this will serve to enhance patient recovery and
      overall satisfaction of neurosurgical patients in the immediate postoperative
      period. TRIAL REGISTRATION: Registered at The Ohio State University Biomedical
      Sciences Institutional Review Board: Protocol Number: 2007 H0053.

PMID- 22862828
TI  - A model to approximate lake temperature from gridded daily air temperature
      records and its application in risk assessment for the establishment of fish
      diseases in the UK.
AB  - Ambient water temperature is a key factor controlling the distribution and impact
      of disease in fish populations, and optimum temperature ranges have been
      characterised for the establishment of a number important aquatic diseases exotic
      to the UK. This study presents a simple regression method to approximate daily
      average surface water temperature in lakes of 0.5-15 ha in size across the UK
      using 5 km(2) gridded daily average air temperatures provided by the UK
      Meteorological Office. A Geographic information system (GIS) is used to present
      thematic maps of relative risk scores established for each grid cell based on the
      mean number of days per year that water temperature satisfied optimal criteria
      for the establishment of two economically important pathogens of cyprinid fish
      (koi herpesvirus (KHV) and spring viraemia of carp virus (SVCV)) and the
      distribution and density of fish populations susceptible to these viruses. High
      density susceptible populations broadly overlap the areas where the temperature
      profiles are optimal for KHV (central and south-east England); however, few fish
      populations occur in areas where temperature profiles are most likely to result
      in the establishment of spring viremia of carp (SVC) (namely northern England and
      Scotland). The highest grid-cell risk scores for KHV and SVC were 7 and 6,
      respectively, out of a maximum score of 14. The proportion of grid cells
      containing susceptible populations with risk scores of 5 or more was 37% and 5%
      for KHV and SVC, respectively. This work demonstrates a risk-based approach to
      inform surveillance for exotic pathogens in aquatic animal health management,
      allowing efficient use of resources directed towards higher risk animals and
      geographic areas for early disease detection. The methodology could be used to
      examine the change in distribution of high-risk areas for both exotic and endemic
      fish diseases under different climate change scenarios. 

PMID- 22862829
TI  - ISAba825 controls the expression of the chromosomal bla(OXA-51-like)  and the
      plasmid borne bla(OXA-58)  gene in clinical isolates of Acinetobacter baumannii
      isolated from the USA.
AB  - Four non-repetitive, clonally related (ST114), carbapenem-resistant Acinetobacter
      baumannii strains isolated in the USA were examined to understand the mechanisms
      of carbapenem resistance including screening for the presence of an insertion
      sequence upstream of the bla(OXA-51-like) gene, which could be involved in the
      control and expression of the antibiotic-resistance gene. We observed that the
      main mechanisms of carbapenem resistance were the result of the over-expression
      of the bla(OXA-58-like) and the bla(OXA-65) gene, both of which had the presence
      of ISAba825 upstream of the genes. The importance of this element was shown by
      isolating plasmid-cured isogenic strains that had lost the plasmid with the
      ISAba825-bla(OXA-58-like) genes but during that same process also lost the
      chromosomal ISAba825 element present upstream of the bla(OXA-65) gene. A 16-fold
      decrease in minimum inhibitory concentration of imipenem and an eight-fold
      decrease in the minimum inhibitory concentration of meropenem were seen in the
      isogenic strains that lost the plasmid. The study presents the first report of
      ISAba825 simultaneously governing the bla(OXA-65) gene and the bla(OXA-58-like)
      gene expression and also highlights the importance of this element in carbapenem
      sensitive isogenic strains, which were once carbapenem resistant.

PMID- 22862830
TI  - Efficient and selective multicomponent oxidative coupling of two different
      aliphatic primary amines into thioamides by elemental sulfur.
AB  - An efficient and selective multicomponent oxidative coupling of two different
      aliphatic primary amines into thioamides by elemental sulfur under solvent-free
      conditions has been developed.

PMID- 22862832
TI  - Super-races are not likely to dominate a fungal population within a life time of
      a perennial crop plantation of cultivar mixtures: a simulation study.
AB  - BACKGROUND: Deployment of cultivars with different resistance in mixtures is one
      means to manage plant diseases and prolong the life of resistance genes. One
      major concern in adopting mixtures is the development of 'super-races' that can
      overcome many resistance genes present in the mixture. A stochastic simulation
      model was developed to study the dynamics of virulence alleles in two-cultivar
      mixtures of perennial crops, focusing on the effects of cost of virulence and
      pathogen reproduction mechanism. The simulated mechanism of virulence has
      characteristics of both major and minor genes. RESULTS: Random genetic drift due
      to repeated population crashes during the overwintering phase led to fixation of
      a single fungal genotype (in terms of its virulence), often within 100 seasons.
      Overall, cost of virulence is most important in determining the virulence
      dynamics under the present model formulation. With cost of virulence
      incorporated, nearly all simulation runs ended up with a single fungal genotype
      that can infect only one of the two cultivars. In absence of cost of virulence,
      most of the simulation runs ended up with fungal genotypes that can infect both
      host cultivars but in many cases do not contain the maximum possible number of
      virulence alleles due to random drift. A minimum of 20% sexual reproduction
      between strains from different cultivars is necessary to ensure that the final
      fixed strains are able to infect both cultivars. Although the number of virulence
      alleles in the final genotype and the time to fixation are affected by simulation
      factors, most of the variability was among replicate simulation runs (i.e.
      stochastic in nature). The time to fixation is generally long relative to
      cropping cycles. CONCLUSIONS: A single fungal genotype will dominate a population
      due to the bottleneck in overwintering with cost of virulence primarily
      determining whether the dominant genotype can infect both cultivars. However, the
      dominant genotype is unlikely to accumulate all the virulence alleles due to
      genetic drift. The risk of emergence and spread of super-races is insufficiently
      great to prevent the use of cultivar mixtures of perennial crops as a means to
      reduce disease development provided that host resistance structure in mixtures is
      altered every cropping cycle.

PMID- 22862833
TI  - What is the most appropriate knowledge synthesis method to conduct a review?
      Protocol for a scoping review.
AB  - BACKGROUND: A knowledge synthesis attempts to summarize all pertinent studies on
      a specific question, can improve the understanding of inconsistencies in diverse
      evidence, and can identify gaps in research evidence to define future research
      agendas. Knowledge synthesis activities in healthcare have largely focused on
      systematic reviews of interventions. However, a wider range of synthesis methods
      has emerged in the last decade addressing different types of questions (e.g.,
      realist synthesis to explore mediating mechanisms and moderators of
      interventions). Many different knowledge synthesis methods exist in the
      literature across multiple disciplines, but locating these, particularly for
      qualitative research, present challenges. There is a need for a comprehensive
      manual for synthesis methods (quantitative/qualitative or mixed), outlining how
      these methods are related, and how to match the most appropriate knowledge
      synthesis method to answer a research question. The objectives of this scoping
      review are to: 1) conduct a systematic search of the literature for knowledge
      synthesis methods across multi-disciplinary fields; 2) compare and contrast the
      different knowledge synthesis methods; and, 3) map out the specific steps to
      conducting the knowledge syntheses to inform the development of a knowledge
      synthesis methods manual/tool. METHODS: We will search relevant electronic
      databases (e.g., MEDLINE, CINAHL), grey literature, and discipline-based
      listservs. The scoping review will consider all study designs including
      qualitative and quantitative methodologies (excluding economic analysis or
      clinical practice guideline development), and identify knowledge synthesis
      methods across the disciplines of health, education, sociology, and philosophy.
      Two reviewers will pilot-test the screening criteria and data abstraction forms,
      and will independently screen the literature and abstract the data. A three-step
      synthesis process will be used to map the literature to our objectives.
      DISCUSSION: This project represents the first attempt to broadly and
      systematically identify, define and classify knowledge synthesis methods (i.e.,
      less traditional knowledge synthesis methods). We anticipate that our results
      will lead to an accepted taxonomy for less traditional knowledge synthesis
      methods, and to the development and implementation of a methods manual for these
      reviews which will be relevant to a wide range of knowledge users, including
      researchers, funders, and journal editors.

PMID- 22862834
TI  - Medical management of Charcot arthropathy.
AB  - Charcot arthropathy is a major complication of diabetes and it poses management
      challenges to health care professionals. Early diagnosis and timely intervention
      are essential for improved outlook of these patients. Casting therapy has been
      accepted as the mainstay treatment of the acute Charcot foot, although there are
      still controversies regarding its duration, the choice of removable and non
      removable device and weight-bearing casts vs. non-weight-bearing casts. Two
      groups of antiresorptive therapies have been evaluated in the treatment of the
      acute Charcot foot, bisphosphonates (intravenous and oral) and calcitonin. These
      therapies have clearly shown a reduction of bone turnover, although, they have
      not shown a significant effect on temperature reduction. Current evidence to
      support their use is weak. An anabolic agent to speed up clinical resolution and
      fracture healing may be helpful and a clinical trial to evaluate the possible
      benefit of 1-84 recombinant human parathyroid hormone on fracture healing in the
      acute Charcot foot is in progress. This paper summarises the current approach to
      medical management of acute Charcot arthropathy with specific emphasis on casting
      and pharmacological therapy. Emerging new studies of the pathogenesis of this
      condition are also discussed.

PMID- 22862831
TI  - Distribution and prediction of catalytic domains in 2-oxoglutarate dependent
      dioxygenases.
AB  - BACKGROUND: The 2-oxoglutarate dependent superfamily is a diverse group of non
      haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea. The
      enzymes differ in substrate preference and reaction chemistry, a factor that
      precludes their classification by homology studies and electronic annotation
      schemes alone. In this work, I propose and explore the rationale of using
      substrates to classify structurally similar alpha-ketoglutarate dependent
      enzymes. FINDINGS: Differential catalysis in phylogenetic clades of 2-OG
      dependent enzymes, is determined by the interactions of a subset of active-site
      amino acids. Identifying these with existing computational methods is challenging
      and not feasible for all proteins. A clustering protocol based on validated
      mechanisms of catalysis of known molecules, in tandem with group specific hidden
      markov model profiles is able to differentiate and sequester these enzymes.
      Access to this repository is by a web server that compares user defined unknown
      sequences to these pre-defined profiles and outputs a list of predicted catalytic
      domains. The server is free and is accessible at the following URL (http://comp
      biol.theacms.in/H2OGpred.html). CONCLUSIONS: The proposed stratification is a
      novel attempt at classifying and predicting 2-oxoglutarate dependent function. In
      addition, the server will provide researchers with a tool to compare their data
      to a comprehensive list of HMM profiles of catalytic domains. This work, will aid
      efforts by investigators to screen and characterize putative 2-OG dependent
      sequences. The profile database will be updated at regular intervals.

PMID- 22862835
TI  - Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5
      HT1A receptors in the dorsal raphe nucleus.
AB  - Cannabidiol is a non-psychotomimetic constituent of Cannabis sativa, which
      induces central effects in rodents. It has been shown that cannabidiol attenuates
      cue-induced reinstatement of heroin seeking. However, to the best of our
      knowledge, its effects on brain stimulation reward and the reward-facilitating
      effects of drugs of abuse have not yet been examined. Therefore, we investigated
      the effects of cannabidiol on brain reward function and on the reward
      facilitating effect of morphine and cocaine using the intracranial self
      stimulation (ICSS) paradigm. Rats were prepared with a stimulating electrode into
      the medial forebrain bundle (MFB), and a guide cannula into the dorsal raphe
      (microinjection experiments), and were trained to respond for electrical brain
      stimulation. A low dose of cannabidiol did not affect the reinforcing efficacy of
      brain stimulation, whereas higher doses significantly elevated the threshold
      frequency required for MFB ICSS. Both cocaine and morphine lowered ICSS
      thresholds. Cannabidiol inhibited the reward-facilitating effect of morphine, but
      not cocaine. This effect was reversed by pre-treatment with an intra-dorsal raphe
      injection of the selective 5-HT1A receptor antagonist WAY-100635. The present
      findings indicate that cannabidiol does not exhibit reinforcing properties in the
      ICSS paradigm at any of the doses tested, while it decreases the reward
      facilitating effects of morphine. These effects were mediated by activation of 5
      HT1A receptors in the dorsal raphe. Our results suggest that cannabidiol
      interferes with brain reward mechanisms responsible for the expression of the
      acute reinforcing properties of opioids, thus indicating that cannabidiol may be
      clinically useful in attenuating the rewarding effects of opioids.

PMID- 22862836
TI  - Validation of an automated chromogenic assay of potency of factor VIII in
      commercial concentrates.
AB  - The determination of factor VIII (FVIII) potency in FVIII concentrates can be
      performed using both manual and automated methods. This work aimed to validate
      the use of the chromogenic kit Coamatic(r) FVIII (Chromogenix) on the automated
      ACL(r) Elite PRO analyzer for evaluating the potency of FVIII in commercial
      preparations in pharmaceutical analytical laboratories. After setting the
      activation and reading times to 2 min and 3 min, respectively, the validation
      parameters, according to the International Conference on Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use
      guideline Q2 (R1), were as follows: linearity, expressed by the adjusted model:
      log (Absorbance) = 1.848 + 0.777?log (Concentration), with r2 = 0.998; accuracy
      was verified (P-value = 0.6959); and the coefficient of variation for
      repeatability and intermediate precision was <=6.5%. The Coamatic(r) FVIII kit
      method has been adapted to the ACL Elite PRO analyzer with improved performance
      compared with a manual microplate method.

PMID- 22862839
TI  - Are residents of downtown Toronto influenced by their urban neighbourhoods? Using
      concept mapping to examine neighbourhood characteristics and their perceived
      impact on self-rated mental well-being.
AB  - BACKGROUND: There is ample evidence that residential neighbourhoods can influence
      mental well-being (MWB), with most studies relying on census or similar data to
      characterize communities. Few studies have actively investigated local residents'
      perceptions. METHODS: Concept mapping was conducted with residents from five
      Toronto neighbourhoods representing low income and non-low income socio-economic
      groups. These residents participated in small groups and attended two sessions
      per neighbourhood. The first session (brainstorming) generated neighbourhood
      characteristics that residents felt influenced their MWB. A few weeks later,
      participants returned to sort these neighbourhood characteristics and rate their
      relative importance in affecting residents' 'good' and 'poor' MWB. The data from
      the sorting and rating groups were analyzed to generate conceptual maps of
      neighbourhood characteristics that influence MWB. RESULTS: While agreement
      existed on factors influencing poor MWB (regardless of neighbourhood, income,
      gender and age), perceptions related to factors affecting good MWB were more
      varied. For example, women were more likely to rank physical beauty of their
      neighbourhood and range of services available as more important to good MWB,
      while men were more likely to cite free access to computers/internet and
      neighbourhood reputation as important. Low-income residents emphasized aesthetic
      attributes and public transportation as important to good MWB, while non-low
      income residents rated crime, negative neighbourhood environment and social
      concerns as more important contributors to good MWB. CONCLUSION: These findings
      contribute to the emerging literature on neighbourhoods and MWB, and inform urban
      planning in a Canadian context.

PMID- 22862840
TI  - Evaluation of thymus morphology and serum cortisol concentration as indirect
      biomarkers to detect low-dose dexamethasone illegal treatment in beef cattle.
AB  - BACKGROUND: Corticosteroids are illegally used in several countries as growth
      promoters in veal calves and beef cattle, either alone or in association with sex
      steroids and beta-agonists, especially at low dosages and primarily through oral
      administration, in order to enhance carcasses and meat quality traits. The aim of
      the present study is to evaluate the reliability of the histological evaluation
      of the thymus, as well as the serum cortisol determination, in identifying beef
      cattle, treated with two different dexamethasone-based growth-promoting protocols
      and the application of different withdrawal times before slaughter. RESULTS: Our
      findings demonstrate that low dosages of dexamethasone (DXM), administered alone
      or in association with clenbuterol as growth promoter in beef cattle, induce
      morphologic changes in the thymus, resulting in increase fat infiltration with
      concurrent cortical atrophy and reduction of the cortex/medulla ratio (C/M). In
      fact, the C/M value was significantly lower in treated animals than in control
      ones, with both the protocols applied. The cut off value of 0.93 for the
      cortex/medulla ratio resulted to be highly effective to distinguish control and
      treated animals. The animals treated with DXM showed inhibition of cortisol
      secretion during the treatment period, as well as at the slaughterhouse, 3 days
      after treatment suspension. The animals treated with lower doses of DXM in
      association with clenbuterol, showed inhibition of cortisol secretion during the
      treatment period, but serum cortisol concentration was restored to physiological
      levels at slaughterhouse, 8 days after treatment suspension. CONCLUSIONS: The
      histological evaluation of thymus morphology, and particularly of the C/M may
      represent a valuable and reproducible method applicable to large-scale screening
      programs, due to the easy sampling procedures at slaughterhouse, as well as time
      and cost-saving of the analysis. Serum cortisol determination could be considered
      as an useful in vivo biomarker of dexamethasone illegal treatment in beef cattle
      during the fattening period, whilst it does not appear to be a good biomarker at
      the slaughterhouse, since the protocol of DXM administration, as well as the
      withdrawal period could affect the reliability of the method.

PMID- 22862837
TI  - Eph receptors and ephrins as targets for cancer therapy.
AB  - Eph receptor tyrosine kinases and their ephrin ligands are involved in various
      signalling pathways and mediate critical steps of a wide variety of physiological
      and pathological processes. Increasing experimental evidence demonstrates that
      both Eph receptor and ephrin ligands are overexpressed in a number of human
      tumours, and are associated with tumour growth, invasiveness and metastasis. In
      this regard, the Eph/ephrin system provides the foundation for potentially
      exciting new targets for anticancer therapies for Eph-expressing tumours. The
      purpose of this review is to outline current advances in the role of Eph
      receptors and ephrin ligands in cancer, and to discuss novel therapeutic
      approaches of anticancer therapies.

PMID- 22862841
TI  - A comparison of different linkage statistics in small to moderate sized pedigrees
      with complex diseases.
AB  - BACKGROUND: In the last years GWA studies have successfully identified common
      SNPs associated with complex diseases. However, most of the variants found this
      way account for only a small portion of the trait variance. This fact leads
      researchers to focus on rare-variant mapping with large scale sequencing, which
      can be facilitated by using linkage information. The question arises why linkage
      analysis often fails to identify genes when analyzing complex diseases. Using
      simulations we have investigated the power of parametric and nonparametric
      linkage statistics (KC-LOD, NPL, LOD and MOD scores), to detect the effect of
      genes responsible for complex diseases using different pedigree structures.
      RESULTS: As expected, a small number of pedigrees with less than three affected
      individuals has low power to map disease genes with modest effect. Interestingly,
      the power decreases when unaffected individuals are included in the analysis,
      irrespective of the true mode of inheritance. Furthermore, we found that the best
      performing statistic depends not only on the type of pedigrees but also on the
      true mode of inheritance. CONCLUSIONS: When applied in a sensible way linkage is
      an appropriate and robust technique to map genes for complex disease. Unlike
      association analysis, linkage analysis is not hampered by allelic heterogeneity.
      So, why does linkage analysis often fail with complex diseases? Evidently, when
      using an insufficient number of small pedigrees, one might miss a true genetic
      linkage when actually a real effect exists. Furthermore, we show that the test
      statistic has an important effect on the power to detect linkage as well.
      Therefore, a linkage analysis might fail if an inadequate test statistic is
      employed. We provide recommendations regarding the most favorable test
      statistics, in terms of power, for a given mode of inheritance and type of
      pedigrees under study, in order to reduce the probability to miss a true linkage.

PMID- 22862842
TI  - Surface contamination of dental implants assessed by gene expression analysis in
      a whole-blood in vitro assay: a preliminary study.
AB  - AIM: We aimed at evaluating pyrogen contamination of dental implants made of
      titanium and zirconia by using gene expression analysis in a whole-blood in vitro
      assay. MATERIAL AND METHODS: Titanium and zirconia implants (five each) were
      incubated in human whole blood. Samples were assayed for gene expression levels
      of toll-like receptor 4 (TLR4), TLR9, interleukin (IL)-1beta, nuclear factor
      'kappa-light-chain-enhancer' of activated B-cells (NF-kB), tumour necrosis factor
      (TNF)-alpha, and Fas-associated protein with death domain (FADD) as indicators of
      surface contamination resulting in lipopolysaccharides (LPS)-stimulated TLR- or
      TNF-mediated immune responses. Gene expression was assayed using real-time
      quantitative polymerase chain reaction (RT-qPCR). Non-stimulated blood from the
      same donor served as a negative control, and blood stimulated with LPS served as
      a positive control. After dry-heat treatment with dry heat, all implants were re
      analysed as described above. RESULTS: Both implant systems contained surface
      contaminants evoking a pro-inflammatory response similar to that induced by LPS.
      After dry-heat treatment, gene expression was significantly decreased to levels
      similar to those of negative control samples. CONCLUSIONS: The results
      demonstrated LPS-like surface-bound contaminants in both tested implant systems.
      Depyrogenation with dry heat seems to be an effective means of reducing such
      contamination in dental implants.

PMID- 22862843
TI  - Detection of haemagglutinin D222 polymorphisms in influenza A(H1N1)pdm09-infected
      patients by ultra-deep pyrosequencing.
AB  - This study was aimed at establishing the genetic heterogeneity of influenza virus
      haemagglutinin (HA) gene quasi-species and the polymorphisms at codon 222, by
      application of ultra-deep pyrosequencing (UDPS) to respiratory samples from
      patients hospitalized for influenza A(H1N1)pdm09 infection, presenting with
      severe or moderate-mild disease. HA diversity was significantly higher in samples
      collected from patients with severe manifestations than in those from patients
      with moderate-mild manifestations (p 0.02). D222 polymorphism was detected in
      40.7% of patients by UDPS, and in only 7.1% by Sanger sequencing. D222E, D222G,
      D222N and D222A were observed in 37.0%, 11.1%, 7.4% and 3.7% of patients,
      respectively; 10.7% of samples harboured more than two variants. The relative
      frequency of each single variant showed a wide range of intrapatient variation.
      D222G/N/A were detected, as either minor or predominant variants, only in severe
      cases, whereas D222E was equally represented in severe and moderate-mild
      infections. Other amino acid variants were observed at different positions within
      the analysed HA fragment. Consistent with higher heterogeneity, non-D222 variants
      were more frequently detected in severe cases than in moderate-mild cases. In
      addition, seven non-D222 mutations carried by minority variants, not previously
      described, were observed.

PMID- 22862844
TI  - Excessive penile norepinephrine level underlies impaired erectile function in
      adenosine A1 receptor deficient mice.
AB  - INTRODUCTION: Penile erection is a complex neurovascular physiological event
      controlled by multiple factors and signaling pathways. A considerable amount of
      evidence indicates that adenosine plays a significant role in cavernosal smooth
      muscle relaxation. However, the specific role of adenosine and its receptors in
      erectile physiology and pathology is not fully understood. AIM: To determine the
      role of the adenosine A1 receptor (ADORA1) in penile erection. METHOD: Adenosine
      A1 receptor deficient (Adora1-/-) mice and aged-matched wild-type (WT) mice were
      utilized. We evaluated the in vivo erectile function by measuring the
      intracavernosal pressure (ICP) in response to cavernous nerve stimulation (CNS).
      Enzyme-linked immunosorbent assay was used to measure the norepinephrine (NE)
      plasma concentration in the corpus cavernosum and systemic circulation. We also
      evaluated the myosin light chain phosphorylation (p-MLC) in penile tissue pre-
      and post-CNS. MAIN OUTCOME MEASUREMENT: The main outcome measurement of this
      research was the evaluation of in vivo erectile response to CNS by measuring the
      ICP in Adora1-/- mice and WT mice and to identify the localization and specific
      neuron types of ADORA1 expression by dual immunostaining and immunofluorescence
      co-localization. RESULT: In vivo, both the ratio of CNS-induced Maximum ICP to
      mean arterial pressure and CNS-induced slope in Adora1-/- mice were significantly
      lower than WT mice. At the cellular level in penile tissue, we determined that
      ADORA1 was highly abundant in neuronal cells. During penile erection, Adora1-/-
      mice exhibited a higher level of NE plasma concentration in the penis than WT
      mice. And WT mice had a significantly greater reduction in p-MLC compared to
      Adora1-/- mice. CONCLUSION: Our results show that ADORA1 is enriched on neuron
      cells where it functions to control NE release. Activation of this receptor
      during penile erection results in reduced NE release and reduced cavernosal
      smooth muscle contraction, therefore facilitating penile erection.

PMID- 22862845
TI  - Peptide binding to HLA-DP proteins at pH 5.0 and pH 7.0: a quantitative molecular
      docking study.
AB  - BACKGROUND: HLA-DPs are class II MHC proteins mediating immune responses to many
      diseases. Peptides bind MHC class II proteins in the acidic environment within
      endosomes. Acidic pH markedly elevates association rate constants but
      dissociation rates are almost unchanged in the pH range 5.0 - 7.0. This pH-driven
      effect can be explained by the protonation/deprotonation states of Histidine,
      whose imidazole has a pK(a) of 6.0. At pH 5.0, imidazole ring is protonated,
      making Histidine positively charged and very hydrophilic, while at pH 7.0
      imidazole is unprotonated, making Histidine less hydrophilic. We develop here a
      method to predict peptide binding to the four most frequent HLA-DP proteins: DP1,
      DP41, DP42 and DP5, using a molecular docking protocol. Dockings to virtual
      combinatorial peptide libraries were performed at pH 5.0 and pH 7.0. RESULTS: The
      X-ray structure of the peptide--HLA-DP2 protein complex was used as a starting
      template to model by homology the structure of the four DP proteins. The
      resulting models were used to produce virtual combinatorial peptide libraries
      constructed using the single amino acid substitution (SAAS) principle. Peptides
      were docked into the DP binding site using AutoDock at pH 5.0 and pH 7.0. The
      resulting scores were normalized and used to generate Docking Score-based
      Quantitative Matrices (DS-QMs). The predictive ability of these QMs was tested
      using an external test set of 484 known DP binders. They were also compared to
      existing servers for DP binding prediction. The models derived at pH 5.0 predict
      better than those derived at pH 7.0 and showed significantly improved predictions
      for three of the four DP proteins, when compared to the existing servers. They
      are able to recognize 50% of the known binders in the top 5% of predicted
      peptides. CONCLUSIONS: The higher predictive ability of DS-QMs derived at pH 5.0
      may be rationalised by the additional hydrogen bond formed between the backbone
      carbonyl oxygen belonging to the peptide position before p1 (p-1) and the
      protonated epsilon-nitrogen of His79beta. Additionally, protonated His residues
      are well accepted at most of the peptide binding core positions which is in a
      good agreement with the overall negatively charged peptide binding site of most
      MHC proteins.

PMID- 22862846
TI  - A prospective study of effects of psychological factors and sleep on obstetric
      interventions, mode of birth, and neonatal outcomes among low-risk British
      Columbian women.
AB  - BACKGROUND: Obstetrical interventions, including caesarean sections, are
      increasing in Canada. Canadian women's psychological states, fatigue, and sleep
      have not been examined prospectively for contributions to obstetric interventions
      and adverse neonatal outcomes.Context and purpose of the study: The prospective
      study was conducted in British Columbia (BC), Canada with 650 low-risk pregnant
      women. Of those women, 624 were included in this study. Women were recruited
      through providers' offices, media, posters, and pregnancy fairs. We examined
      associations between pregnant women's fatigue, sleep deprivation, and
      psychological states (anxiety and childbirth fear) and women's exposure to
      obstetrical interventions and adverse neonatal outcomes (preterm, admission to
      NICU, low APGARS, and low birth weight). METHODS: Data from our cross-sectional
      survey were linked, using women's personal health numbers, to birth outcomes from
      the Perinatal Services BC database. After stratifying for parity, we used
      Pearson's Chi-square to examine associations between psychological states,
      fatigue, sleep deprivation and maternal characteristics. We used hierarchical
      logistic regression modeling to test 9 hypotheses comparing women with high and
      low childbirth fear and anxiety on likelihood of having epidural anaesthetic, a
      caesarean section (stratified for parity), assisted vaginal delivery, and adverse
      neonatal outcomes and women with and without sleep deprivation and high levels of
      fatigue on likelihood of giving birth by caesarean section, while controlling for
      maternal, obstetrical (e.g., infant macrosomia), and psychological variables.
      RESULTS: Significantly higher proportions of multiparas, reporting difficult and
      upsetting labours and births, expectations of childbirth interventions, and
      health stressors, reported high levels of childbirth fear. Women who reported
      antenatal relationship, housing, financial, and health stressors and multiparas
      reporting low family incomes were significantly more likely to report high
      anxiety levels. The hypothesis that high childbirth fear significantly increased
      the risk of using epidural anaesthesia was supported. CONCLUSIONS: Controlling
      for some psychological states and sleep quality while examining other
      contributors to outcomes decreases the likelihood of linking childbirth fear
      anxiety, sleep deprivation, and fatigue to increased odds of caesarean section.
      Ameliorating women's childbirth fear to reduce their exposure to epidural
      anaesthesia can occur through developing effective interventions. These include
      helping multiparous women process previous experiences of difficult and upsetting
      labour and birth.

PMID- 22862847
TI  - Weight change with liraglutide and comparator therapies: an analysis of seven
      phase 3 trials from the liraglutide diabetes development programme.
AB  - AIM: We investigated the relationship between weight change and related factors
      in subjects with type 2 diabetes mellitus (T2DM) treated with liraglutide versus
      comparator diabetes therapies. METHODS: Twenty-six-week data from seven phase 3,
      randomized trials in the liraglutide T2DM development programme were analysed by
      trial and treatment group: liraglutide (1.2 and 1.8 mg), active comparator and
      placebo. Outcome measures included proportions of subjects in various weight
      change categories and their percentage weight change from baseline; impact of
      body mass index (BMI) and gastrointestinal (GI) adverse events (AEs) on weight
      change and correlation of weight change with change in glycosylated haemoglobin
      (HbA1c). RESULTS: A number of subjects experienced >5% weight loss during the
      trials (24.4% liraglutide 1.8 mg and 17.7% liraglutide 1.2 mg; 17.7% exenatide,
      10.0% sitagliptin, 3.6-7.0% sulphonylurea, 2.6% thiazolidinedione and 2.6%
      glargine; 9.9% placebo). More weight loss was seen with liraglutide 1.2 and 1.8
      mg than with active comparators except exenatide. Across trials, higher initial
      BMI was associated with slightly greater weight loss with liraglutide. Mean
      weight loss increased slightly the longer GI AEs persisted. Although HbA1c
      reduction was slightly larger in higher weight loss categories across treatments
      (including placebo), sample sizes were small and no clear correlation could be
      determined. Liraglutide-treated subjects experienced additional HbA1c reduction
      beyond that which appeared weight induced; thus, not all HbA1c-lowering effect
      appears weight mediated. CONCLUSIONS: The majority of liraglutide-treated T2DM
      subjects experienced weight loss in this analysis. Weight loss was greater and
      occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than
      in active comparator-treated subjects.

PMID- 22862848
TI  - Solvent-induced single-crystal-to-single-crystal transformation in
      multifunctional chiral dysprosium(III) compounds.
AB  - Two new enantiomeric ionic chiral dysprosium(III) compounds were designed and
      synthesized. These compounds show simultaneously the optical activity,
      ferroelectric effects, nonlinear-optical effects, and slow magnetic relaxation
      behavior. More interestingly, these compounds exhibit reversible single-crystal
      to-single-crystal transformations associated with the release or absorption of
      solvent molecules. The structure transformations are accompanied by distinct
      changes in the physical properties.

PMID- 22862849
TI  - Response to genomic selection: the Bulmer effect and the potential of genomic
      selection when the number of phenotypic records is limiting.
AB  - BACKGROUND: Over the last ten years, genomic selection has developed enormously.
      Simulations and results on real data suggest that breeding values can be
      predicted with high accuracy using genetic markers alone. However, to reach high
      accuracies, large reference populations are needed. In many livestock populations
      or even species, such populations cannot be established when traits are difficult
      or expensive to record, or when the population size is small. The value of
      genomic selection is then questionable. METHODS: In this study, we compare
      traditional breeding schemes based on own performance or progeny information to
      genomic selection schemes, for which the number of phenotypic records is
      limiting. Deterministic simulations were performed using selection index theory.
      Our focus was on the equilibrium response obtained after a few generations of
      selection. Therefore, we first investigated the magnitude of the Bulmer effect
      with genomic selection. RESULTS: Results showed that the reduction in response
      due to the Bulmer effect is the same for genomic selection as for selection based
      on traditional BLUP estimated breeding values, and is independent of the accuracy
      of selection. The reduction in response with genomic selection is greater than
      with selection based directly on phenotypes without the use of pedigree
      information, such as mass selection. To maximize the accuracy of genomic
      estimated breeding values when the number of phenotypic records is limiting, the
      same individuals should be phenotyped and genotyped, rather than genotyping
      parents and phenotyping their progeny. When the generation interval cannot be
      reduced with genomic selection, large reference populations are required to
      obtain a similar response to that with selection based on BLUP estimated breeding
      values based on own performance or progeny information. However, when a genomic
      selection scheme has a moderate decrease in generation interval, relatively small
      reference population sizes are needed to obtain a similar response to that with
      selection on traditional BLUP estimated breeding values. CONCLUSIONS: When the
      trait of interest cannot be recorded on the selection candidate, genomic
      selection schemes are very attractive even when the number of phenotypic records
      is limited, because traditional breeding requires progeny testing schemes with
      long generation intervals in those cases.

PMID- 22862850
TI  - Brain region- and sex-specific alterations in DAMGO-stimulated [(35) S]GTPgammaS
      binding in mice with Oprm1 A112G.
AB  - The A118G single nucleotide polymorphism (SNP) of the human MU-opioid receptor
      (MOPR) gene (OPRM1) was associated with heightened dopamine release by alcohol
      intake, better treatment outcome for nicotine and alcohol addiction, and reduced
      analgesic responses to morphine. A mouse model that possesses the equivalent
      substitution (A112G) in the mouse MOPR gene (OPRM1) was generated to delineate
      the mechanisms of the impact of the SNP. Mice homozygous for the G112 allele
      (G/G) displayed lower morphine-induced antinociception than mice homozygous for
      the A112 allele (A/A), similar to the results in humans. In this study, we
      examined whether A112G SNP affected MOPR-mediated G protein activation in the
      mouse model. We compared A/A and G/G mice in the MOPR-selective agonist [D-Ala2,
      N-MePhe4, Gly-ol]-enkephalin (DAMGO)-stimulated [(35) S]GTPgammaS binding in
      brain regions by autoradiography. When the data of males and females were
      combined, G/G mice exhibited lower DAMGO-stimulated [(35) S]GTPgammaS binding in
      the ventral tegmental area than A/A mice, in accord with the previously reported
      reduced morphine-induced hyperactivity and locomotor sensitization in G/G mice.
      In the nucleus accumbens (NAc) core, female G/G mice displayed lower DAMGO
      stimulated [(35) S]GTPgammaS binding than female A/A mice, which is consistent
      with the previously reported deficiency in morphine-induced conditioned place
      preference in female G/G mice. In G/G mice, males showed higher DAMGO-stimulated
      [(35) S]GTPgammaS binding than females in the cingulate cortex, caudate putamen,
      NAc core, thalamus and amygdala. Thus, A112G SNP affects DAMGO-stimulated [(35)
      S]GTPgammaS binding in region- and sex-specific manners. 

PMID- 22862851
TI  - Predicting waist circumference from body mass index.
AB  - BACKGROUND: Being overweight or obese increases risk for cardiometabolic
      disorders. Although both body mass index (BMI) and waist circumference (WC)
      measure the level of overweight and obesity, WC may be more important because of
      its closer relationship to total body fat. Because WC is typically not assessed
      in clinical practice, this study sought to develop and verify a model to predict
      WC from BMI and demographic data, and to use the predicted WC to assess
      cardiometabolic risk. METHODS: Data were obtained from the Third National Health
      and Nutrition Examination Survey (NHANES) and the Atherosclerosis Risk in
      Communities Study (ARIC). We developed linear regression models for men and women
      using NHANES data, fitting waist circumference as a function of BMI. For
      validation, those regressions were applied to ARIC data, assigning a predicted WC
      to each individual. We used the predicted WC to assess abdominal obesity and
      cardiometabolic risk. RESULTS: The model correctly classified 88.4% of NHANES
      subjects with respect to abdominal obesity. Median differences between actual and
      predicted WC were -0.07 cm for men and 0.11 cm for women. In ARIC, the model
      closely estimated the observed WC (median difference: -0.34 cm for men, +3.94 cm
      for women), correctly classifying 86.1% of ARIC subjects with respect to
      abdominal obesity and 91.5% to 99.5% as to cardiometabolic risk.The model is
      generalizable to Caucasian and African-American adult populations because it was
      constructed from data on a large, population-based sample of men and women in the
      United States, and then validated in a population with a larger representation of
      African-Americans. CONCLUSIONS: The model accurately estimates WC and identifies
      cardiometabolic risk. It should be useful for health care practitioners and
      public health officials who wish to identify individuals and populations at risk
      for cardiometabolic disease when WC data are unavailable.

PMID- 22862853
TI  - Evaluation of CytoDiffTM on cord blood WBC differential.
AB  - INTRODUCTION: An umbilical cord blood bank was recently opened in our institution
      as an alternative source of hematopoietic stem cells. Before inclusion of a cord
      blood in an international register, a WBC with differential is requested, among
      others. Currently, the reference method is the microscopic manual count, and we
      sought to evaluate the routine flow cytometric method (CytoDiffTM) as an
      alternative. METHODS: A total of 161 cord bloods were analyzed between November
      2010 and February 2011. WBC differentials were determined for each sample, by (i)
      the cell counter (DxH800), (ii) a manual review, and (iii) the flow cytometry
      using the CytoDiffTM antibody cocktail. RESULTS: Correlation coefficients between
      flow cytometry and microscopic count were satisfying for neutrophils,
      lymphocytes, and immature granulocytes and acceptable for eosinophils. On the
      other hand, we found lower correlation coefficient for basophils and monocytes.
      Monocytes' correlation was better when comparing flow cytometry with cell
      counter. CONCLUSION: The flow cytometric approach is suitable to realize cord
      blood WBC differential and allows for the identification of additional cell
      subsets.

PMID- 22862852
TI  - Diabetes influences cardiac extracellular matrix remodelling after myocardial
      infarction and subsequent development of cardiac dysfunction.
AB  - This study was conducted to examine the influence of acute streptozotocin-induced
      diabetes on cardiac remodelling and function in mice subjected to myocardial
      infarction (MI) by coronary artery ligation. Echocardiography analysis indicated
      that diabetes induced deleterious cardiac functional changes as demonstrated by
      the negative differences of ejection fraction, fractional shortening, stroke
      volume, cardiac output and left ventricular volume 24 hrs after MI. Temporal
      analysis for up to 2 weeks after MI showed higher mortality in diabetic animals
      because of cardiac wall rupture. To examine extracellular matrix remodelling, we
      used fluorescent molecular tomography to conduct temporal studies and observed
      that total matrix metalloproteinase (MMP) activity in hearts was higher in
      diabetic animals at 7 and 14 days after MI, which correlated well with the degree
      of collagen deposition in the infarct area visualized by scanning electron
      microscopy. Gene arrays indicated temporal changes in expression of distinct MMP
      isoforms after 1 or 2 weeks after MI, particularly in diabetic mice. Temporal
      changes in cardiac performance were observed, with a trend of exaggerated
      dysfunction in diabetic mice up to 14 days after MI. Decreased radial and
      longitudinal systolic and diastolic strain rates were observed over 14 days after
      MI, and there was a trend towards altered strain rates in diabetic mouse hearts
      with dyssynchronous wall motion clearly evident. This correlated with increased
      collagen deposition in remote areas of these infarcted hearts indicated by
      Masson's trichrome staining. In summary, temporal changes in extracellular matrix
      remodelling correlated with exaggerated cardiac dysfunction in diabetic mice
      after MI.

PMID- 22862854
TI  - Soft tissue response to zirconia and titanium implant abutments: an in vivo
      within-subject comparison.
AB  - AIM: To compare the health of the soft tissues towards zirconia and titanium
      abutments in man, as observed using histological data. MATERIAL AND METHODS:
      Twenty patients received two mandibular implants with either a zirconia or
      titanium abutment (split mouth study design, left-right randomization). After 3
      months soft tissue biopsies were prepared for histological evaluation. They were
      subjected to blind evaluation. The number of blood vessels per surface unit and
      an inflammation grading scale score ranging from 1 to 4 were determined. RESULTS:
      Paired samples from 17 patients were suitable for analysis, 3 with unsevered
      implant-abutment connections and 14 solely containing soft tissue. All showed a
      well-keratinized stratified squamous epithelium which was continuous with the
      barrier (junctional) epithelium that faced the abutment surface. The normal
      epithelial build-up could be recognized with little signs of inflammation. No
      statistically significant difference in tissues adjacent to zirconia and titanium
      abutment surfaces were seen with respect to vascular density (20.5 SD 4.4 and
      20.7 SD 3.2) or inflammation grading scale scores (3.2 SD 0.7 versus 3.1 SD 0.7).
      CONCLUSION: No differences in soft tissue health were seen in peri-implant mucosa
      adjacent to zirconia and titanium abutment surfaces.

PMID- 22862855
TI  - Echocardiography of the normal camel (Camelus dromedaries) heart: technique and
      cardiac dimensions.
AB  - BACKGROUND: Echocardiography and intra-cardiac dimensions have not previously
      been reported in adult camels despite its potential application for medical
      purpose. The aim of this study was to describe the results of a prospective
      study, aiming to report normal cardiac appearance and normal chamber dimensions
      in adult camels (Camelus dromedarius). RESULTS: On the right side, when the probe
      was placed in the 5th or 4th intercostal space (ICS), the caudal long-axis four
      chamber view of the ventricles, atria, and the interventricular septum was
      obtained. Placing the probe slightly more cranially in the 4th ICS, the caudal
      long-axis four-chamber view and the caudal long-axis view of the left ventricular
      outflow tract (LVOT) were imaged. In 7 camels, a hybrid view between a "four
      chamber" and "LVOT view" was imaged from the same position. The short-axis view
      of the ventricles was obtained in the 4th ICS where the transducer was rotated
      between 0 degrees  and 25 degrees . Placement of the transducer in the 3rd ICS
      allowed visualisation of the right ventricular outflow tract (RVOT). On the left
      side, when the probe was placed in the 5th or 4th ICS, a four-chamber view was
      obtained. The LVOT is imaged in the 4th ICS and the RVOT was seen from the 3rd
      ICS. CONCLUSIONS: This study showed that it is possible to obtain good-quality
      echocardiograms in adult camels and provide normal cardiac dimensions. This study
      could be used as a reference for further studies concerning camels with cardiac
      diseases.

PMID- 22862856
TI  - Genetic diversity of equine gammaherpesviruses (gamma-EHV) and isolation of a
      syncytium forming EHV-2 strain from a horse in Iceland.
AB  - The horse population in Iceland is a special breed, isolated from other equines
      for at least one thousand years. This provides an exceptional opportunity to
      investigate old and new pathogens in a genetically closed herd. Both types of
      equine gammaherpesviruses, EHV-2 and EHV-5, are common in Iceland. Genetic
      variation was examined by sequencing four genes, glycoprotein B (gB),
      glycoprotein H (gH), DNA polymerase and DNA terminase for 12 Icelandic and seven
      foreign EHV-2 strains. One Icelandic virus isolate, gEHV-Dv, induced syncytium
      formation, an uncharacteristic cytopathy for EHV-2 in equine kidney cells. When
      sequenced, the glycoprotein genes were different from both EHV-2 and EHV-5, but
      the polymerase and terminase genes had 98-99% identity to EHV-2. Therefore the
      gEHV-Dv strain can be considered a variant of EHV-2. Substantial genetic
      variability was seen within the EHV-2 glycoprotein genes but limited in the
      polymerase and terminase genes. The Icelandic EHV-2 strains do not seem to differ
      phylogenetically from the foreign viruses, despite isolation for over a thousand
      years.

PMID- 22862857
TI  - The potential of Medicare accountable care organizations to transform the
      American health care marketplace: rhetoric and reality.

PMID- 22862858
TI  - Accountable care organization pathways: diverse but ultimately parallel.

PMID- 22862859
TI  - Ascension health partners with Centers for Medicare and Medicaid Services to
      provide patient-centered care through the Pioneer Accountable Care Organization
      model.

PMID- 22862860
TI  - A modified "Golden Rule" for health care organizations.

PMID- 22862861
TI  - Building an accountable care organization for all the wrong reasons.

PMID- 22862862
TI  - Why Baylor Health Care System would like to file for Medicare Shared Savings
      accountable care organization designation but cannot.

PMID- 22862863
TI  - A physician hospital organization's approach to clinical integration and
      accountable care.

PMID- 22862864
TI  - The SSM Health Care approach to achieving "True North": improving health care
      quality while reducing costs.

PMID- 22862866
TI  - 46-year-old man with fevers, chills, and pancytopenia.

PMID- 22862867
TI  - Opioid substitution therapy for dependent health care practitioners: approach
      with caution.

PMID- 22862865
TI  - The Princeton III Consensus recommendations for the management of erectile
      dysfunction and cardiovascular disease.
AB  - The Princeton Consensus (Expert Panel) Conference is a multispecialty
      collaborative tradition dedicated to optimizing sexual function and preserving
      cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010,
      and had 2 primary objectives. The first objective focused on the evaluation and
      management of cardiovascular risk in men with erectile dysfunction (ED) and no
      known cardiovascular disease (CVD), with particular emphasis on identification of
      men with ED who may require additional cardiologic work-up. The second objective
      focused on reevaluation and modification of previous recommendations for
      evaluation of cardiac risk associated with sexual activity in men with known CVD.
      The Panel's recommendations build on those developed during the first and second
      Princeton Consensus Conferences, first emphasizing the use of exercise ability
      and stress testing to ensure that each man's cardiovascular health is consistent
      with the physical demands of sexual activity before prescribing treatment for ED,
      and second highlighting the link between ED and CVD, which may be asymptomatic
      and may benefit from cardiovascular risk reduction.

PMID- 22862868
TI  - Incomplete reporting in a case report of corticosteroids in the treatment of
      alcohol-induced rhabdomyolysis.

PMID- 22862869
TI  - Buprenorphine maintenance therapy in opioid-addicted health care professionals.

PMID- 22862870
TI  - Buprenorphine maintenance therapy in opioid-addicted health care professionals
      returning to clinical practice: a hidden controversy.

PMID- 22862872
TI  - Buprenorphine maintenance therapy in opioid-addicted health care professionals
      returning to clinical practice.

PMID- 22862874
TI  - Why vitamin D status should be checked in patients with nonalcoholic fatty liver
      disease.

PMID- 22862876
TI  - Catherine Verfaillie--stem cell researcher.

PMID- 22862877
TI  - Complete lumbar dislocation after a car crash.

PMID- 22862878
TI  - Generation of a selectively cytotoxic fusion protein against p53 mutated cancers.
AB  - BACKGROUND: A significant number of cancers are caused by defects in p21 causing
      functional defects in p21 or p53 tumour-suppressor proteins. This has led to many
      therapeutic approaches including restoration by gene therapy with wild-type p53
      or p21 using viral or liposomal vectors, which have toxicity or side-effect
      limitations. We set out to develop a safer, novel fusion protein which has the
      ability to reconstitute cancer cell lines with active p21 by protein
      transduction. METHODS: The fusion protein was produced from the cell
      translocating peptide Antennapedia (Antp) and wild-type, full-length p21 (Antp
      p21). This was expressed and refolded from E. coli and tested on a variety of
      cell lines and tumours (in a BALB/c nude xenograft model) with differing p21 or
      p53 status. RESULTS: Antp-p21 penetrated and killed cancer cells that do not
      express wild type p53 or p21. This included cells that were matched to cogenic
      parental cell lines. Antp-p21 killed cancer cells selectively that were malignant
      as a result of mutations or nuclear exclusion of the p53 and p21 genes and over
      expression of MDM2. Non-specific toxicity was excluded by showing that Antp-p21
      penetrated but did not kill p53- or p21- wild-type cells. Antp-p21 was not
      immunogenic in normal New Zealand White rabbits. Recombinant Antp peptide alone
      was not cytotoxic, showing that killing was due to the transduction of the p21
      component of Antp-p21. Antp-p21 was shown to penetrate cancer cells engrafted in
      vivo and resulted in tumour eradication when administered with conventionally
      used chemotherapeutic agents, which alone were unable to produce such an effect.
      CONCLUSIONS: Antp-p21 may represent a new and promising targeted therapy for
      patients with p53-associated cancers supporting the concept that rational design
      of therapies directed against specific cancer mutations will play a part in the
      future of medical oncology.

PMID- 22862879
TI  - Treatment persistence, hypoglycaemia and clinical outcomes in type 2 diabetes
      patients with dipeptidyl peptidase-4 inhibitors and sulphonylureas: a primary
      care database analysis.
AB  - AIMS: To investigate therapy persistence, frequency of hypoglycaemia and
      macrovascular outcomes among type 2 diabetes patients with dipeptidyl peptidase-4
      (DPP-4) inhibitors (DPP-4) and sulphonylureas (SU). METHODS: Data from 19,184 DPP
      4 (mean age: 64 years; 56% males) and 31,110 SU users (69 years; 51%) with new
      prescriptions (index date), without additional antidiabetics except metformin, in
      1201 general practises in Germany were analysed. Therapy discontinuation
      (prescription gap >90 days), hypoglycaemia [International Classification of
      Diseases (ICD-10)] and macrovascular outcomes (ICD-10) (2-year follow-up) were
      compared adjusting for age, sex, diabetes duration, metformin, previous
      hypoglycaemia, health insurance, hypertension, hyperlipidaemia,
      antihypertensives, lipid-lowering and antithrombotic drugs, microvascular
      complications and Charlson co-morbidity score using logistic or Cox regression
      models. RESULTS: Two years after index date, DDP-4 (non-persistence: 39%) were
      associated with a lower risk of discontinuation compared to SU (49%) [adjusted
      hazard ratio (HR): 0.74; 95% confidence interval (CI): 0.71-0.76]. Hypoglycaemias
      (>=1) were documented in 0.18% patients with DPP-4 and in 1.00% with SU [odds
      ratio (OR): 0.21; 95%CI: 0.08-0.57]. Hypoglycaemias were significantly associated
      with incident macrovascular complications (HR: 1.6; 95% CI: 1.1-2.2). Risk of
      macrovascular events was 26% lower in DPP-4 than in SU users. CONCLUSIONS: Lack
      of persistence with antidiabetic therapy is frequently found in primary care
      patients. DPP-4 was associated with lower therapy discontinuation and a fivefold
      reduced frequency of patients with hypoglycaemia compared to SU. The low absolute
      numbers of hypoglycaemias are most likely due to the fact that only severe events
      were documented. DPP-4 treatment was associated with reduced incidence of
      macrovascular events relative to SU in type 2 diabetes patients in primary care
      practises.

PMID- 22862880
TI  - New chiral zinc complexes: synthesis, structure, and induction of axial
      chirality.
AB  - We describe an efficient methodology for the preparation of new chiral zinc
      complexes by assembling dynamically racemic biphenol derivatives and chiral 1,2
      diamines with suitable zinc(II) precursors. Mononuclear and dinuclear zinc(II)
      complexes were formed from differently substituted biphenols. The solid-state and
      solution structural characterization of the resulting compounds allowed us to
      demonstrate a preferential sense of induced axial chirality for mononuclear
      complexes, a phenomenon that was not observed for the dinuclear ones.

PMID- 22862881
TI  - Bartonella henselae-mediated disease in solid organ transplant recipients: two
      pediatric cases and a literature review.
AB  - Bartonella henselae, the etiologic agent of cat-scratch disease, causes a well
      defined, self-limited syndrome of fever and regional lymphadenopathy in
      immunocompetent hosts. In immunocompromised hosts, however, B. henselae can cause
      severe disseminated disease and pathologic vasoproliferation known as bacillary
      angiomatosis (BA) or bacillary peliosis. BA was first recognized in patients
      infected with human immunodeficiency virus. It has become more frequently
      recognized in solid organ transplant (SOT) recipients, but reports of pediatric
      cases remain rare. Our review of the literature revealed only one previously
      reported case of BA in a pediatric SOT recipient. We herein present 2 pediatric
      cases, one of which is the first reported case of BA in a pediatric cardiac
      transplant recipient, to our knowledge. In addition, we review and summarize the
      literature pertaining to all cases of B. henselae-mediated disease in SOT
      recipients.

PMID- 22862882
TI  - Surgical treatment of liver metastases of gastric cancer: state of the art.
AB  - BACKGROUND: The prognosis of patients with liver metastases from gastric cancer
      (LMGC) is dismal, and little is known about prognostic factors in these patients;
      so justification for surgical resection is still controversial. Furthermore the
      results of chemotherapy for these patients are disappointing. The purpose of this
      study was to review recent outcomes of hepatectomy for LMGC and to determine the
      suitable candidates for surgery, assessing the surgical results and
      clinicopathologic features. Moreover we compare these results with those obtained
      with alternative treatments.

PMID- 22862883
TI  - Prevalence and diversity of Babesia spp. in questing Ixodes ricinus ticks from
      Norway.
AB  - BACKGROUND: Ixodes ricinus ticks transmit Babesia species to vertebrate hosts.
      Using molecular tools we were able to detect the presence of this piroplasmid in
      its vector. The aims of this study were to investigate the prevalence and
      identity of Babesia species in questing ticks collected in various areas of
      Norway. METHODS: DNA from questing l. ricinus ticks were examined with a realtime
      PCR for the presence of Babesia. Positive samples of tick DNA were identified to
      species using PCR, and sequence analysis. RESULTS: From a total of 1908 questing
      l. ricinus ticks, 17 (0.9%) indicated the presence of Babesia spp. after realtime
      PCR screening. Ixodes ricinus harbouring Babesia spp. was detected in 9 out of 22
      localities. Further molecular analyses of DNA from these positive ticks indicate
      the presence of Babesia venatorum, B. divergens, B. capreoli and a currently
      undescribed Babesia in Norwegian ticks. The most prevalent was B. venatorum found
      in 71% of the positive ticks. CONCLUSIONS: A total of 17 out of 1908 (0.9%) ticks
      were positive for Babesia. Our data confirm that there are several Babesia
      species in ticks in Norway. Babesia venatorum was the most prevalent. This
      species has a zoonotic potential and may cause human babesiosis following a tick
      bite.

PMID- 22862884
TI  - How to generalize efficacy results of randomized trials: recommendations based on
      a systematic review of possible approaches.
AB  - RATIONALE, AIMS AND OBJECTIVES: Randomized controlled trials (RCTs) are the
      preferred source for evidence for the effect of treatment. However, patients
      participating in RCTs often manifest important differences from patients seen in
      practice. Therefore, guideline developers have to decide whether the results are
      generalizable to the target population not represented in RCTs. METHOD: A
      systematic review of the literature was undertaken to identify methods to decide
      whether to generalize the results from RCTs to patients who were not represented
      in these trials. RESULTS: One approach is to examine the in- and exclusion
      criteria of trials and infer from these whether the trial population was
      sufficiently representative. Other authors suggest, because of the inclusion of a
      broader range of patients, reliance on observational studies if no direct
      evidence for the target population is available. Another approach is to apply the
      relative effect of treatment found in trials to patients in practice unless there
      is a compelling reason to believe the results would differ substantially as a
      function of particular characteristics of those patients. Although there are
      exceptions, this approach is supported by empirical evidence that, in general,
      relative effect of treatment on benefit outcomes seldom differs to an important
      extent across subgroups of patients. CONCLUSION: We propose this last approach:
      focusing on RCTs unless there is a compelling reason not to do so. Compelling
      reasons will most often be found with respect to issues of rare adverse effects,
      for which observational studies are likely to provide the best estimates.

PMID- 22862885
TI  - Prevalence of the HPA-18w to -21w alleles in the Chinese Han population.
AB  - Recently, four new platelet alloantigen (HPA) systems HPA-18w to-21w were
      identified. However, genotyping for HPA-18w to -21w alleles was rarely reported.
      Here, we established a polymerase chain reaction sequence-based typing (PCR-SBT)
      method and investigated the distribution of HPA-18w to -21w alleles in the
      Chinese Han population. The specific primers of HPA-18w, -19w, -20w and -21w were
      designed, and the PCR products were bidirectionally sequenced. 855 randomly
      selected platelet donors were genotyped for HPA-18w to -21w with the PCR-SBT
      method. The results showed that all individuals were monomorphic for HPA-18w to
      HPA-20w with a/a homozygous frequency of 1.0 and absence of HPA-18bw to -20bw
      alleles. The frequencies of the HPA-21a/21a and HPA-21a/21b genotypes were
      0.981(839/855) and 0.019(16/855), respectively. Seven mutations were confirmed on
      sequenced region separate from HPA polymorphisms, including ITGA2 (IVS17+48G>A
      and IVS17+72G>A), ITGA2B (IVS19-26C>G) and ITGB3 (IVS4+234C>T, IVS11-19 T>C,
      IVS11-104T>C and GT repeats from IVS11-131 to IVS11-109). These data will provide
      useful information for diagnosis, prevention and treatment of alloimmune
      thrombocytopaenia.

PMID- 22862886
TI  - Somatic differentiation and MR imaging of magnetically labeled human embryonic
      stem cells.
AB  - Magnetic resonance (MR) imaging of superparamagnetic iron oxide (SPIO)-labeled
      stem cells offers a noninvasive evaluation of stem cell engraftment in host
      organs. Excessive cellular iron load from SPIO labeling, however, impairs stem
      cell differentiation. The purpose of this study was  to magnetically label human
      embryonic stem cells (hESCs) via a reduced exposure protocol that maintains a
      significant MR signal and no significant impairment to cellular pluripotency or
      differentiation potential. hESCs were labeled by simple incubation with Food and
      Drug Administration-approved  ferumoxides, using concentrations of 50- 200 ug
      Fe/ml and incubation times of 3-24 h. The most reduced exposure labeling protocol
      that still provided a significant MR signal comparable to accepted labeling
      protocols was selected for subsequent studies. Labeled hESCs were  compared to
      unlabeled controls for differences in pluripotency as studied by fluorescence
      staining for SSEA-1, SSEA-4, TRA-60, and TRA-81 and in differentiation capacity
      as studied by quantitative real-time PCR for hOCT4, hACTC1, hSOX1, and hAFP after
      differentiation into embryoid bodies (EBs).  Subsequent MR and microscopy imaging
      were performed to evaluate for cellular iron distribution and long-term
      persistence of the label. An incubation concentration of 50 ug Fe/ml and
      incubation time of 3 h demonstrated a significantly reduced exposure protocol
      that yielded an intracellular  iron uptake of 4.50 +/- 0.27 pg, an iron content
      comparable to currently accepted SPIO labeling protocols. Labeled and unlabeled
      hESCs showed no difference in pluripotency or differentiation capacity.
      Ferumoxide-labeled hESCs demonstrated persistent MR contrast effects as embryoid
      bodies  for 21 days. Electron microscopy confirmed persistent lysosomal storage
      of iron oxide particles in EBs up to 9 days, while additional microscopy
      visualization confirmed the iron distribution within single and multiple EBs.
      Labeling hESCs with ferumoxides by this tailored protocol reduces exposure  of
      cells to the labeling agent while allowing for long-term visualization with MR
      imaging and the retention of cellular pluripotency and differentiation potential.

PMID- 22862887
TI  - Household smoking, maternal atopy and allergic sensitization in children: is it
      all academic?

PMID- 22862888
TI  - Novel cardiovascular risk markers in depression: no association between
      depressive symptoms and osteoprotegerin or adiponectin in persons at high risk
      for sleep apnea.
AB  - BACKGROUND: Inflammation is believed to play a role in the pathogenesis of both
      cardiovascular disease and depressive disorders. We hypothesized that circulating
      concentrations of the novel inflammatory and cardiovascular biomarkers
      osteoprotegerin (OPG) and adiponectin as well as high sensitivity C-reactive
      protein (hsCRP) are associated with the severity of depressive symptoms and
      presence of major depressive disorder (MDD). METHODS: In a cross-sectional
      population-derived study (Akershus Sleep Apnea Project) 520 persons underwent
      clinical examination and venous blood sampling. Medical history was obtained and
      the participants completed the Beck Depression Inventory (BDI). Structured
      clinical interviews for axis-I disorders including MDD were performed in a
      subgroup of 288 participants. OPG and adiponectin concentrations were determined
      by in-house time-resolved immunofluorometric assays. RESULTS: Despite significant
      correlation with hsCRP (r=0.162, p<0.001), the sum-score of BDI did not correlate
      with OPG or adiponectin levels (r=0.011, p=0.811 and r=0.055, p=0.210,
      respectively). Neither circulating OPG nor adiponectin differed between persons
      with (n=34) and without (n=246) MDD (median+/-interquartile range: 1.18 (0.96
      1.49) vs. 1.17 (0.93-1.57) ug/l and 7.26 (5.13-9.91) vs. 7.39 (5.23-11.37) mg/l,
      respectively). LIMITATIONS: Causal considerations are not possible, and results
      in the sub-group of diagnosed participants need careful interpretation due to
      small sample size. CONCLUSIONS: hsCRP was independently associated with
      depressive symptoms, but no association between depression severity or presence
      of MDD and OPG- or adiponectin concentrations was observed in community-residing
      persons at high risk for obstructive sleep apnea.

PMID- 22862889
TI  - A test of the Interpersonal Theory of Suicide in a large community-based cohort.
AB  - BACKGROUND: Joiner's Interpersonal Theory of Suicide (Van Orden et al., 2010;
      Joiner, 2005) predicts that suicide ideation is strongest in those experiencing
      both high perceived burdensomeness and thwarted belongingness, and that the
      combination of suicide ideation and acquired capability for suicide is critical
      in the development of suicide plans and attempts. However, few datasets exist
      which allow the examination of these predictions. The present study aimed to test
      predictions from the model in a population-based cohort. METHODS: a survey was
      completed by 6133 participants from the PATH Through Life Project. Scales
      measuring perceived burdensomeness, thwarted belongingness, hopelessness,
      capability to self-injure, ideation, plans and attempts were developed using
      existing items. Regression models were used to predict the outcomes of ideation
      and of plans/attempts. RESULTS: consistent with the Interpersonal Theory,
      interactions were found between perceived burdensomeness and thwarted
      belongingness predicting ideation, and interactions of capability and ideation
      for plans/attempts. However, some predictions of the theory were not fulfilled.
      Nevertheless, the Interpersonal Theory explained more variance than
      epidemiological models using mental disorders as predictors. Age differences were
      evident, with models of older cohorts accounting for less variance. Gender models
      suggested thwarted belongingness was a stronger predictor of ideation in males
      than females. LIMITATIONS: while the fit of the factors assessing the
      Interpersonal Theory was adequate, the findings will need to be confirmed using
      previously developed scales of these constructs. CONCLUSIONS: predictive models
      of suicide need to take into account multiple risk factors, gender differences
      and changes in associations over the life span.

PMID- 22862890
TI  - Towards a clinical staging for bipolar disorder: defining patient subtypes based
      on functional outcome.
AB  - BACKGROUND: The functional outcome of Bipolar Disorder (BD) is highly variable.
      This variability has been attributed to multiple demographic, clinical and
      cognitive factors. The critical next step is to identify combinations of
      predictors that can be used to specify prognostic subtypes, thus providing a
      basis for a staging classification in BD. METHODS: Latent Class Analysis was
      applied to multiple predictors of functional outcome in a sample of 106 remitted
      adults with BD. RESULTS: We identified two subtypes of patients presenting "good"
      (n=50; 47.6%) and "poor" (n=56; 52.4%) outcome. Episode density, level of
      residual depressive symptoms, estimated verbal intelligence and inhibitory
      control emerged as the most significant predictors of subtype membership at the
      p<0.05 level. Their odds ratio (OR) and confidence interval (CI) with reference
      to the "good" outcome group were: episode density (OR=4.622, CI 1.592-13.418),
      level of residual depressive symptoms (OR=1.543, CI 1.210-1.969), estimated
      verbal intelligence (OR=0.969; CI 0.945-0.995), and inhibitory control (OR=0.771,
      CI 0.656-0.907). Age, age of onset and duration of illness were comparable
      between prognostic groups. LIMITATIONS: The longitudinal stability or evolution
      of the subtypes was not tested. CONCLUSIONS: Our findings provide the first
      empirically derived staging classification of BD based on two underlying
      dimensions, one for illness severity and another for cognitive function. This
      approach can be further developed by expanding the dimensions included and
      testing the reproducibility and prospective prognostic value of the emerging
      classes. Developing a disease staging system for BD will allow individualised
      treatment planning for patients and selection of more homogeneous patient groups
      for research purposes.

PMID- 22862892
TI  - Oral healthcare of preschool children in Trinidad: a qualitative study of parents
      and caregivers.
AB  - BACKGROUND: Little is known about oral health in early childhood in the West
      Indies or the views and experiences of caregivers about preventive oral care and
      dental attendance The aims of this study were to explore and understand parents
      and caregivers' experience of oral healthcare for their preschool aged children
      and how, within their own social context, this may have shaped their oral health
      attitudes and behaviours. These data can be used to inform oral health promotion
      strategies for this age group. METHOD: After ethical approval, a qualitative
      study was undertaken using a focus group approach with a purposive sample of
      parents and caregivers of preschool children in central Trinidad.Group
      discussions were initiated by use of a topic guide. Audio recording and field
      notes from the three focus groups, with a total of 18 participants, were
      transcribed and analysed using a thematic approach. RESULTS: Despite some
      ambivalence toward the importance of the primary teeth, the role of fluoride and
      confusion about when to take a child for their first dental visit, most
      participants understood the need to ensure good oral hygiene and dietary habits
      for their child. Problems expressed included, overcoming their own negative
      experiences of dentistry, which along with finding affordable and suitable dental
      clinics, affected their attitude to taking their child for a dental visit. There
      was difficulty in establishing good brushing routines and controlling sweet
      snacking in the face of many other responsibilities at home. Lack of availability
      of paediatric dental services locally and information on oral health care were
      also highlighted. Many expressed a need for more contact with dental
      professionals in non-clinic settings, for oral health care advice and guidance.
      CONCLUSION: Parents and caregivers in this qualitative study showed generally
      positive attitudes towards oral health but appear to have encountered several
      barriers and challenges to achieving ideal preventive care for their child, with
      respect to healthy diet, good oral hygiene and dental attendance. Oral health
      promotion should include effective dissemination of oral health information, more
      practical health advice and greater access to dental care for families with
      preschool children.

PMID- 22862893
TI  - A longitudinal study of pain and pain catastrophizing in a cohort of National
      Guard troops at risk for PTSD.
AB  - A recent cross-sectional study of National Guard troops found that pain and pain
      catastrophizing were prevalent and highly correlated with posttraumatic stress
      disorder (PTSD). At issue in the present study was whether pain and
      catastrophizing before military deployment could account for individual
      differences in PTSD symptoms after deployment. An anonymous survey was
      administered to a population sample of New Jersey National Guard troops before
      they were sent overseas and again when they returned home (1 year later). The
      survey included a validated PTSD screening questionnaire, numerical ratings of
      pain intensity, and a measure of pain catastrophizing. A cohort of 922 National
      Guard members completed the survey before and after deployment. An uncontrolled
      analysis indicated that pain and catastrophizing before deployment were
      significantly but modestly associated with PTSD symptoms after deployment
      (accounting for 4.5% and 1.3% of the variance, respectively). A hierarchical
      regression model that controlled for sex, preexisting PTSD symptoms, and recent
      combat found that pain but not pain catastrophizing explained variance in
      postdeployment PTSD. The size of the effect, however, was negligible (0.8%,
      p<.01). Consistent with previous research, a cross-sectional analysis revealed
      that postdeployment pain and catastrophizing successfully accounted for unique
      variance in postdeployment PTSD. The failure of longitudinal predictors in the
      present study, therefore, cannot be attributed to insensitive screening
      instruments. These findings offer little or no support for the hypothesis that
      predeployment pain and catastrophizing can account for individual differences in
      PTSD after exposure to combat trauma.

PMID- 22862891
TI  - Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP)
      project: study design and methods for pooling results of genetic epidemiological
      studies.
AB  - BACKGROUND: For complex diseases like cancer, pooled-analysis of individual data
      represents a powerful tool to investigate the joint contribution of genetic,
      phenotypic and environmental factors to the development of a disease. Pooled
      analysis of epidemiological studies has many advantages over meta-analysis, and
      preliminary results may be obtained faster and with lower costs than with
      prospective consortia. DESIGN AND METHODS: Based on our experience with the study
      design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic
      characteristics (M-SKIP) project, we describe the most important steps in
      planning and conducting a pooled-analysis of genetic epidemiological studies. We
      then present the statistical analysis plan that we are going to apply, giving
      particular attention to methods of analysis recently proposed to account for
      between-study heterogeneity and to explore the joint contribution of genetic,
      phenotypic and environmental factors in the development of a disease. Within the
      M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31
      international investigators were checked for quality and recoded for
      standardization. We first proposed to fit the aggregated data with random-effects
      logistic regression models. However, for the M-SKIP project, a two-stage analysis
      will be preferred to overcome the problem regarding the availability of different
      study covariates. The joint contribution of MC1R variants and phenotypic
      characteristics to skin cancer development will be studied via logic regression
      modeling. DISCUSSION: Methodological guidelines to correctly design and conduct
      pooled-analyses are needed to facilitate application of such methods, thus
      providing a better summary of the actual findings on specific fields.

PMID- 22862894
TI  - Identification of a novel Baeyer-Villiger monooxygenase from Acinetobacter
      radioresistens: close relationship to the Mycobacterium tuberculosis prodrug
      activator EtaA.
AB  - This work demonstrates that Acinetobacter radioresistens strain S13 during the
      growth on medium supplemented with long-chain alkanes as the sole energy source
      expresses almA gene coding for a Baeyer-Villiger monooxygenase (BVMO) involved in
      alkanes subterminal oxidation. Phylogenetic analysis placed the sequence of this
      novel BVMO in the same clade of the prodrug activator ethionamide monooxygenase
      (EtaA) and it bears only a distant relation to the other known class I BVMO
      proteins. In silico analysis of the 3D model of the S13 BVMO generated by
      homology modelling also supports the similarities with EtaA by binding
      ethionamide to the active site. In vitro experiments carried out with the
      purified enzyme confirm that this novel BVMO is indeed capable of typical Baeyer
      Villiger reactions as well as oxidation of the prodrug ethionamide.

PMID- 22862895
TI  - Regulation of PUMA induced by mechanical stress in rat cardiomyocytes.
AB  - BACKGROUND: PUMA (p53-up-regulated modulator of apoptosis), an apoptosis
      regulated gene, increased during endoplasmic reticulum stress. However, the
      expression of PUMA in cardiomyocytes under mechanical stress is little known. We
      aimed to investigate the regulation mechanism of PUMA expression and apoptosis
      induced by mechanical stress in cardiomyocytes. METHODS: Aorta-caval (AV) shunt
      was performed in adult Wistar rats to induce volume overload. Rat neonatal
      cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60
      cycles/min. RESULTS: PUMA protein and mRNA were up-regulated in the shunt group
      as compared with sham group. The increased PUMA protein expression and apoptosis
      induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day
      orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited
      the apoptosis induced by volume overload. Cyclic stretch significantly enhanced
      PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK)
      inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-gamma (INF
      gamma) antibody 30 min before stretch reduced the induction of PUMA protein. Gel
      shift assay demonstrated that stretch increased the DNA binding activity of
      interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid,
      SP600125 and INF-gamma antibody abolished the PUMA promoter activity induced by
      stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA
      and atorvastatin. CONCLUSIONS: Mechanical stress enhanced apoptosis and PUMA
      expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA
      expression and apoptosis induced by mechanical stress in cardiomyocytes.

PMID- 22862896
TI  - Diagnostic yield of tuberculosis using sputum induction in HIV-positive patients
      before antiretroviral therapy.
AB  - Adults (n = 602) enrolling in a South African antiretroviral treatment clinic
      underwent culture-based screening for tuberculosis (TB), regardless of symptoms.
      For those unable to spontaneously expectorate a 'spot' sample (n = 124), sputum
      induction with nebulised  hypertonic saline was used to obtain a first sample and
      also to rapidly obtain a second sample from all patients. Collection of both
      samples typically took 10-15 min. The prevalence of culture-positive TB was 15.6%
      (95%CI 12.8-18.8). Spontaneously expectorated spot samples yielded  79.8% of all
      culture-positive TB diagnoses. The incremental yield from those needing an
      induced first sample was 5.3% and the yield from induced second samples was
      14.9%.

PMID- 22862897
TI  - High risk alcohol-related trauma among the Aboriginal and Torres Strait Islanders
      in the Northern Territory.
AB  - High risk drinking is linked with high rates of physical harm. The reported
      incidence of alcohol - related trauma among Aboriginal and Torres Strait Islander
      people in the Northern Territory is the highest in the world. Facial fractures
      are common among young Aboriginal and Torres Strait Islanders. They are often
      linked with misuse of alcohol in the Northern Territory and are frequently
      secondary to assault. This review focuses on alcohol-related trauma in the
      Territory and draws attention to an urgent need for preventative health approach
      to address this critical issue.

PMID- 22862898
TI  - Racial disparities in voice outcomes after thyroid and parathyroid surgery.
AB  - BACKGROUND: There is evidence that the outcomes of head and neck surgery may
      differ across racial and ethnic groups. Vocal changes related to the operation
      are an anticipated risk of thyroidectomy and parathyroidectomy. Race-specific
      voice outcomes after thyroid and parathyroid operations have not been reported.
      Therefore, our aim was to examine the potential disparity in voice outcomes
      between white and black patients after thyroid or parathyroid operations.
      PATIENTS AND METHODS: Eighty-seven patients (59 white and 28 black) were included
      in a prospective observational trial. Subjects were evaluated before operation,
      and 2 weeks, 3 months, and 6 months postoperatively using a comprehensive battery
      of functional voice assessments of voice characteristics. The association of race
      with voice outcomes over time was evaluated with generalized linear models.
      RESULTS: Aside from volume of pathologic specimen (black, 117.5 cm3 vs. white,
      43.2 cm3; P = .004), presence of multinodular goiter (black, 32.1% vs. white,
      6.8%; P = .004) or Hashimoto's thyroiditis (black, 3.6% vs. white, 28.8%; P =
      .009), there were no differences between racial groups. Blacks were more likely
      than whites to have negative voice outcomes (odds ratio, 2.6; 95% confidence
      interval, 1.1-6.2; P = .034] throughout the postoperative period, especially at 6
      months (black, 25% vs. white, 4%; P = .018). This finding was related principally
      to divergent scores on the voice-related quality-of-life scale, the voice
      handicap index. CONCLUSION: We observed greater rates of self-reported, negative
      voice outcomes among blacks than whites after thyroid or parathyroid operations.
      The precise mechanism for this disparity has not been described. The observed
      racial disparity in self-perceived voice impairment in this study merits further
      investigation.

PMID- 22862899
TI  - Angiogenesis is crucial for liver regeneration after partial hepatectomy.
AB  - BACKGROUND: Recent studies of hepatic regeneration have mainly focused on the
      growth of parenchymal cells. However, remodeling of liver vessels seems to be
      crucial during hepatic regeneration. In this study, we investigated the influence
      of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for
      vascular endothelial growth factor that acts as a dominant negative receptor, and
      the hepatocyte growth factor antagonist NK4. METHODS: A sFlt-1-expressing
      adenoviral vector, an NK4-expressing adenoviral vector, or both combined were
      infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was
      performed on all of the mice 48 hours after infection. The remnants of the liver
      were removed after the partial hepatectomy, and hepatic regeneration was assessed
      by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine
      staining, immunohistochemical staining with anti-platelet endothelial cell
      adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies
      for angiogenic factors. RESULTS: The immunohistochemical staining for CD31 showed
      suppression of sinusoidal endothelial cells growth in sFlt-1-expressing
      adenoviral vector-and NK4-expressing adenoviral vector-infected mice. Increases
      in the remnant hepatic weight were significantly lower in the sFlt-1-expressing
      adenoviral vector-infected mice. The bromodeoxyuridine index and mitotic cell
      results revealed a significant decrease in hepatic regeneration in the sFlt-1
      expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice.
      The suppressive effects on hepatic regeneration were significantly enhanced by
      combined sFlt-1-expressing adenoviral vector and NK4-expressing adenoviral vector
      infection. Real-time polymerase chain reaction results revealed the significant
      suppression of angiogenic growth factor receptors Tie-1 and Tie-2. CONCLUSION:
      The angiogenesis inhibitor significantly suppressed hepatic regeneration. These
      results suggest that hepatic regeneration after hepatectomy closely correlates
      with angiogenesis.

PMID- 22862901
TI  - Evaluation of high-risk, comorbid patients undergoing open ventral hernia repair
      with synthetic mesh.
AB  - BACKGROUND: The Ventral Hernia Working Group proposed recently a classification
      system to grade the risk of surgical site occurrence (SSO) during ventral hernia
      repair (VHR). Accurately predicting the outcomes of synthetic mesh in open VHR
      for comorbid patients might guide surgeons in appropriate mesh selection in this
      patient population. Our objective was to determine the incidence of SSO in open,
      grade II VHR and to examine the use of synthetic mesh in these comorbid patients.
      METHODS: All open, grade II VHR performed by a single surgeon over a 4-year
      period were reviewed retrospectively. RESULTS: Eighty-eight patients (43 female;
      mean age, 57 years) with grade II ventral hernias underwent open VHR with
      synthetic mesh. Associated comorbidities included obesity in 55 (63%), diabetes
      mellitus in 43 (49%), chronic obstructive pulmonary disease in 27 (31%), smoking
      in 21 (24%), and immunosuppression in 18 (21%). The mean number of comorbidities
      per patient was 1.9 (range, 1-4). SSO occurred in 14 (16%) patients and included
      infection (n = 11), seroma (n = 2), and wound dehiscence (n = 1). Having multiple
      comorbidities was associated with an increased risk of SSO (P = .02). Three (3%)
      patients required reoperation or readmission for wound management. With a mean
      follow-up of 17.8 months, 4 (5%) patients developed a hernia recurrence.
      CONCLUSION: Patients with grade II hernias undergoing open VHR are prone to SSO
      with an incidence of 16%. Although synthetic mesh infections can occur among
      grade II patients, the majority can be managed conservatively with salvage of the
      prosthesis, especially if macroporous mesh is used. Given our findings, the use
      of synthetic mesh in the retrorectus space results in a safe and durable (5%
      recurrence rate) repair for patients with grade II incisional hernias.

PMID- 22862900
TI  - The intestinal environment of surgical injury transforms Pseudomonas aeruginosa
      into a discrete hypervirulent morphotype capable of causing lethal peritonitis.
AB  - BACKGROUND: Secondary peritonitis continues to carry a high mortality rate
      despite the aggressive use of imaging, drainage, and antibiotics. Although host
      factors and microbial burden contribute to the outcome of peritonitis, we propose
      a role for bacterial virulence as a determinant of outcome from peritonitis.
      Bacterial virulence is an inducible trait that is activated in response to
      specific local "cues" that we have previously shown to be present in the mouse
      gut exposed to surgical stress and injury. METHODS: Pseudomonas aeruginosa was
      harvested after its intestinal inoculation into the cecum of mice subjected to
      surgical injury (30% hepatectomy) or sham surgery (controls). Harvested strains
      were then injected into the peritoneum of noninjured (naive) mice and mortality
      determined. RESULTS: P. aeruginosa harvested from the intestines of surgically
      injured mice caused 100% mortality, whereas strains harvested from control mice
      caused no mortality. Among recovered strains, a distinct P. aeruginosa morphotype
      (wrinkled shape) was shown to cause lethal peritonitis compared to smooth-shaped
      strains, which were nonlethal. Wrinkled strains were associated with a tendency
      to elicit a more proinflammatory response in mice compared to smooth-shaped
      strains. CONCLUSION: Surgical injury transforms the morphotype of intestinal P.
      aeruginosa to express a hypervirulent response in the peritoneum of mice.
      Enhanced virulence of intestinal pathogens in response to surgical injury may
      play an important role in predicting the outcome of peritonitis.

PMID- 22862902
TI  - Sutureless fixation with fibrin glue of lightweight mesh in open inguinal hernia
      repair: effect on postoperative pain: a double-blind, randomized trial versus
      standard heavyweight mesh.
AB  - BACKGROUND: Open inguinal hernia repair is associated with a low incidence of
      complications that can be influenced by the type of mesh and its method of
      fixation. Our aim was to investigate the frequency and severity of postoperative
      pain and other complications when lightweight, large-pore meshes, compared with
      heavyweight, small-pore meshes, are fixed with human fibrin glue (HFG) during
      open inguinal hernia repair. METHODS: A cohort of 80 patients undergoing open
      inguinal repair were enrolled. Forty patients received a lightweight and large
      porous mesh and 40 a standard heavyweight mesh with small pores. In all patients,
      HFG was used for mesh fixation. RESULTS: Patients who received lightweight, large
      pore mesh reported less pain than those in the control group both postoperatively
      (2.8 +/- 1.1 vs. 4.9 +/- 1.1; P = .0003) and at 1-month follow-up (1.7 +/- 1.0
      vs. 3.1 +/- 1.0; P = .0038), and took fewer analgesics. There was no difference
      in days off work/activity. No differences were observed concerning postoperative
      complications. After 6 months there was no difference in groin pain between
      groups. CONCLUSION: Patients who underwent open inguinal hernia repair with
      lightweight, large-pore mesh fixed with HFG experienced less pain throughout the
      first month after operation compared with those receiving standard mesh.

PMID- 22862903
TI  - Game theory: applications for surgeons and the operating room environment.
AB  - BACKGROUND: Game theory is an economic system of strategic behavior, often
      referred to as the "theory of social situations." Very little has been written in
      the medical literature about game theory or its applications, yet the practice of
      surgery and the operating room environment clearly involves multiple social
      situations with both cooperative and non-cooperative behaviors. METHODS: A
      comprehensive review was performed of the medical literature on game theory and
      its medical applications. Definitive resources on the subject were also examined
      and applied to surgery and the operating room whenever possible. RESULTS:
      Applications of game theory and its proposed dilemmas abound in the practicing
      surgeon's world, especially in the operating room environment. CONCLUSION: The
      surgeon with a basic understanding of game theory principles is better prepared
      for understanding and navigating the complex Operating Room system and optimizing
      cooperative behaviors for the benefit all stakeholders.

PMID- 22862904
TI  - Role of bone marrow and mesenchymal stem cells in healing after traumatic injury.
AB  - BACKGROUND: The role of bone marrow-derived cells (BMDCs) and mesenchymal stem
      cells (MSC) in healing of traumatic-induced injury remains poorly understood.
      Mesenteric lymph duct ligation (LDL) results in decreased BMDC mobilization and
      impaired healing. We hypothesized that LDL-mediated impaired healing would be
      abrogated by reinjection of BMDC or MSC. METHODS: Sprague-Dawley rats were
      subjected to LDL + lung contusion (LC+LDL) with or without injection of BMDCs or
      MSCs. Unmanipulated control (UC) and lung contusion alone (LC) served as
      controls. BMDC and MSC homing was assessed by hematopoietic progenitor cell (HPC
      [granulocyte-, erythrocyte-, monocyte-, and megakaryocyte colony-forming units;
      erythroid burst-forming units; and erythroid colony-forming units]) colony growth
      and immunofluorescent microscopic tracking of tagged MSC, respectively.
      Histologic lung injury score (LIS) was used to grade injury. Data are mean +/-
      SD. *P < .05/Student t test. RESULTS: Lung HPC growth was decreased in LC+LDL
      versus LC alone (HPC colonies: 2 +/- 2, 4 +/- 3, 4 +/- 2 vs. 11 +/- 2, 20 +/- 6,
      22 +/- 9. *P < .05). LC+LDL had greater degree of lung injury on days 5 and 7 LC
      alone (LIS: 5 +/- 1, 4 +/- 1 vs. 3 +/- 1, 1 +/- 0.4. *P < .05). BMDC injection
      into rats with LC + LDL increased lung HPC growth to LC level (HPC colonies: 12
      +/- 2, 19 +/- 5, 17 +/- 4 vs 11 +/- 2, 20 +/- 6, 22 +/- 9. P > .05). Injected
      MSCs into LC+LDL rats homed preferentially to contused versus noncontused lung
      (MSC/high-powered field: 6 +/- 4 vs. 2 +/- 2 *P < .05). Either BMDC or MSC
      injection into LC+LDL rats returned lung injury to LC level on day 7 (LIS: 1 +/-
      0.4 and 1 +/- 1 vs. 1 +/- 0.4. P > .05). CONCLUSION: LDL-mediated impaired tissue
      healing is abrogated by either whole BMDC or MSC injection. This highlights the
      critical role of BMDC and MSC on healing of trauma-induced injury.

PMID- 22862905
TI  - Primary synovial sarcoma of the parapharyngeal space: a clinicopathologic study
      of five cases.
AB  - We report five cases of primary synovial sarcomas arising in the parapharyngeal
      space. The patients were all men with a median age of 35 years (range 22 to 41
      years). The tumors were non-encapsulated solid masses ranging from 2.0 to 6.6 cm
      in size. Histologically, three cases were biphasic subtype, and the other two
      cases were monophasic subtype. Immunohistochemically, the tumor cells were
      strongly positive for bcl-2 and CD99, partly positive for CK and EMA, and
      negative for CD117, CD34, SMA and desmin in all five cases. S-100 protein was
      detected in one case. The presence of an SYT-SSX1 and/or SYT-SSX2 gene fusion
      resulting from t(X;18) was demonstrated from paraffin blocks by reverse
      transcriptase polymerase chain reaction in five cases. All five patients received
      tumor radical excision and postoperative radiotherapy, and two patients with
      pulmonary metastasis received additional chemotherapy. Follow-up data revealed
      that two patients with tumor size <5 cm were alive without disease for 54 and 57
      months, one patient with tumor size <5 cm was alive with pulmonary metastasis for
      78 months, and two patients with tumor size >5 cm died of disease 26 and 37
      months after the diagnosis, respectively. Primary parapharyngeal synovial sarcoma
      is a rare variant that occurs more frequently in males than females. Accurate
      diagnosis depends on morphologic and immunohistochemical examination and proper
      molecular analysis. The prognosis is relatively good in those patients whose
      tumor size is less than 5 cm.

PMID- 22862906
TI  - Online group-based cognitive-behavioural therapy for adolescents and young adults
      after cancer treatment: a multicenter randomised controlled trial of Recapture
      Life-AYA.
AB  - BACKGROUND: A cancer diagnosis is 2.9 times more likely to occur during the
      adolescent and young adult years than in younger children. This spike in
      incidence coincides with a life stage characterised by psychological
      vulnerability as young people strive to attain numerous, critical developmental
      milestones. The distress young people experience after cancer treatment seriously
      jeopardises their ability to move into well-functioning adulthood.
      METHODS/DESIGN: This article presents the protocol of the Recapture Life study, a
      phase II three-arm randomised controlled trial designed to evaluate the
      feasibility and efficacy of a new intervention in reducing distress and improving
      quality of life for adolescent and young adult cancer survivors. The novel
      intervention, "ReCaPTure LiFe" will be compared to a both a wait-list, and a peer
      support group control. Ninety young people aged 15-25 years who have completed
      cancer treatment in the past 1-6 months will be recruited from hospitals around
      Australia. Those randomised to receive Recapture Life will participate in six,
      weekly, 90-minute online group sessions led by a psychologist, involving peer
      discussion around cognitive-behavioural coping skills (including: behavioural
      activation, thought challenging, communication and assertiveness skills training,
      problem-solving and goal-setting). Participants randomised to the peer-support
      group control will receive non-directive peer support delivered in an identical
      manner. Participants will complete psychosocial measures at baseline, post
      intervention, and 12-months post-intervention. The primary outcome will be
      quality of life. Secondary outcomes will include depression, anxiety, stress,
      family functioning, coping, and cancer-related identity. DISCUSSION: This article
      reviews the empirical rationale for using group-based, online cognitive
      behavioural therapy in young people after cancer treatment. The potential
      challenges of delivering skills-based programs in an online modality are
      highlighted, and the role of both peer and caregiver support in enhancing the
      effectiveness of this skills-based intervention is also discussed. The innovative
      videoconferencing delivery method Recapture Life uses has the potential to
      address the geographic and psychological isolation of adolescents and young
      adults as they move toward cancer survivorship. It is expected that teaching AYAs
      coping skills as they resume their normal lives after cancer may have long-term
      implications for their quality of life. TRIAL REGISTRATION: ACTRN12610000717055.

PMID- 22862907
TI  - Neutropenic enterocolitis after high-dose chemotherapy and autologous stem cell
      transplantation: incidence, risk factors, and outcome.
AB  - BACKGROUND: Neutropenic enterocolitis (NE) is a life-threatening complication
      occurring after intensive chemotherapy; however, no data are available on NE
      development after hematopoietic stem cell transplantation (SCT). The aim of this
      study was to determine the incidence, risk factors, and outcome of NE after high
      dose chemotherapy and autologous SCT (autoSCT). METHODS: A total of 297 adult
      patients who qualified for autoSCT with non-Hodgkin's lymphoma (NHL), Hodgkin's
      disease, multiple myeloma, and acute myeloid leukemia were analyzed. Patients
      were conditioned with carmustine, etoposide, cytarabine, melphalan (BEAM);
      melphalan alone; or busulfan and cyclophosphamide (BuCy2), and transplanted with
      peripheral blood or bone marrow CD34(+) cells. Diagnosis of NE was established in
      case of neutropenic fever, abdominal pain or diarrhea, and bowel wall thickening
      >4 mm on abdominal sonography. RESULTS: Neutropenic infections occurred in 262
      patients (88%). NE was diagnosed in 32 patients (12%), a median +3 (1-5) days
      after SCT. Bloodstream infections were present in 18 patients, with gram-negative
      bacteria in 11 patients. All patients were treated conservatively with
      carbapenems and total parenteral nutrition with bowel rest. The course of disease
      was complicated by ileus or septic shock in 9 patients, and was fatal for 3
      (9.6%) patients. In univariate analysis, the initial diagnosis of NHL (P = 0.017)
      and conditioning with BEAM (P = 0.043) had prognostic value. In multivariate
      analysis, only initial diagnosis of NHL (P = 0.017) had prognostic significance.
      CONCLUSIONS: NE is a rare but severe complication in patients undergoing autoSCT.
      Gram-negative bacteria remain the main causative pathogen. Abdominal sonography
      allows early diagnosis and treatment, effective in most of patients without
      surgery. In our analysis, NE was seen more often in NHL patients treated with a
      BEAM regimen.

PMID- 22862908
TI  - Hypofractionated radiotherapy for T1N0M0 glottic cancer: retrospective analysis
      of two different cohorts of dose-fractionation schedules from a single
      institution.
AB  - AIMS: To determine the influence of dose and fractionation on tumour
      characteristics, toxicity, disease control and survival outcomes in T1 glottic
      carcinoma. MATERIALS AND METHODS: Between 1975 and 2000, treatment charts of 652
      patients with T1 glottic carcinoma who received curative radiation with four
      hypofractionated schedules (50 Gy/15 fractions [3.3 Gy/fraction] or 55 Gy/16
      fractions [3.43 Gy/fraction] or 60 Gy/24 fractions or 62.5 Gy/25 fractions [2.5
      Gy/fraction]) were analysed. The patients were divided into two groups based on
      fraction size <3 Gy and >3 Gy. Local control and overall survival were
      calculated. Patient- and tumour-related factors affecting local control were
      analysed using univariate and multivariate analysis. Factors affecting late
      toxicity were also analysed. RESULTS: The local control and overall survival at
      10 years were 84 and 86.1%, respectively, for T1 glottic carcinoma. The response
      to radiation had a significant effect on local control with univariate analysis
      (P = 0.001). Other factors, such as beam energy, anterior commissure involvement
      and fractionation, did not affect local control. Persistent radiation oedema was
      seen in 123 patients (23.4%) and was significantly worse in patients who received
      radiation with a larger field size (>36 cm(2)) on a telecobalt machine (P <
      0.001). CONCLUSIONS: Radical radiotherapy schedules incorporating a higher dose
      per fraction yield acceptable local control rates and late toxicity. Telecobalt
      therapy for early glottic cancer is a safe alternative to treatment with 6 MV
      photons on a linear accelerator in terms of local control and late toxicity as
      long as field sizes smaller than 36 cm(2) are used.

PMID- 22862909
TI  - Outcomes of vitrified early cleavage-stage and blastocyst-stage embryos in a
      cryopreservation program: evaluation of 3,150 warming cycles.
AB  - OBJECTIVE: To assess the outcomes achieved after Cryotop vitrification of both
      early cleavage and blastocyst-stage embryos and to determine whether the embryo
      developmental stage and embryo quality as well as the origin of the embryos (ovum
      donation cycles, patients' own oocytes) and the endometrial preparation for the
      embryo transfer had any effect on the final outcome. DESIGN: Observational study.
      SETTING: Private university-affiliated IVF center. PATIENT(S): Women undergoing
      3,150 warming cycles whose embryos were vitrified due to various reasons.
      INTERVENTION(S): Vitrification by the Cryotop open device. MAIN OUTCOME
      MEASURE(S): Delivery rate (DR) per warming cycle. RESULT(S): Survival rate was
      95% (5,722 out of 6,019 embryos). The percentage of intact embryos at warming
      showing 100% blastomere survival was 93% (95% CI 90.1%-95.3%) for day 2 and 95%
      (95% CI 94.3%-95.7%) for day 3; 3,057 embryo transfers were performed (3%
      cancellation rate). The DR/warming cycle was 32.5% (95% CI 30.9%-34.2%). Slight
      differences in survival rate were found [94.9% (95% CI 93.0%-96.8%) for day 2,
      94.2% (95% CI 93.4%-94.9%) for day 3, 95.7% (95% CI 94.5%-96.9%) for day 5, and
      97.6% (95% CI 96.9%-98.6%) for day 6]. Overall implantation, clinical pregnancy,
      ongoing pregnancy, and live birth rates per warming cycle were 35.5% (95% CI
      33.5%-38.5%), 41.7% (95% CI 39.9%-43.4%), 32.6% (95% CI 31.0%-34.2%), and 38.1%
      (95% CI 36.4%-39.8%) respectively. The linear regression model considering embryo
      developmental stage, ovum donation or patient's own oocytes, and hormonal
      replacement therapy or natural cycle for endometrial preparation (odds ratio
      1.179; 95% CI 0.912-1.277) showed no impact on the DR. CONCLUSION(S): Highly
      successful cryopreservation of all embryo developmental stages is possible with
      the use of the Cryotop system. There are no variables clearly exerting a negative
      effect on the survival and delivery rates.

PMID- 22862910
TI  - Time perception disorders are related to working memory impairment in
      schizophrenia.
AB  - Time perception (TP) impairment in schizophrenia has been originally described by
      clinicians and afterwards addressed in laboratory. Previous studies generally
      observed that schizophrenia patients overestimate time and that their timing
      sensitivity is impaired. However, because of the disease cognitive impairments,
      no study until now allows to draw definitive conclusions about the nature of TP
      disturbances. The aim of this study is to isolate a genuine TP disorder in
      schizophrenia, i.e., a disorder that would be related to the functioning of an
      internal clock. The main hypothesis tested is that patients' internal clock runs
      faster than that of healthy controls. Twenty-five patients suffering from a first
      episode of schizophrenia and twenty-five healthy controls performed an innovative
      task called method of dynamic stimuli, designed to measure the natural frequency
      (F(n)) of the internal clock, concomitant with a neuropsychological assessment.
      We observed no significant difference in F(n) between groups. Compared to
      controls, there was a marginally higher variability in time reproduction in
      patients. Patients' pattern of results and significant correlations between TP
      tasks and memory outcomes suggest that TP impairments are related to memory
      impairment in schizophrenia. These conclusions are supported by a growing
      literature showing that cognition is involved in TP in schizophrenia.

PMID- 22862911
TI  - Depressive and anxiety disorders on-the-job: the importance of job
      characteristics for good work functioning in persons with depressive and anxiety
      disorders.
AB  - This study examines the importance of job characteristics on absence and on-the
      job performance in a large group of employees with diagnosed depressive and
      anxiety disorders. In a sample of 1522 employees (1129 persons with and 393
      persons without psychopathology) participating in Netherlands Study of Depression
      and Anxiety (NESDA, n=2981) we examined associations between job characteristics
      and work functioning (absenteeism and work performance) in multinominal logistic
      regression models. Job characteristics were working hours, psychosocial working
      conditions and occupational status. As expected, depressed and anxious patients
      were at significantly elevated risk for absenteeism and poor work performance. In
      analyses adjusted for psychopathology, absenteeism and poor performance were
      significantly lower among persons reporting high job support, high job control,
      less working hours, self-employed and high skilled jobs. Associations were
      comparable between persons with and without psychopathology. High job support,
      high job control and reduced working hours were partially related to work
      functioning in both workers with- and without-psychopathology. Since depressed
      and anxious employees are at a substantially increased risk for absenteeism and
      poor work performance, strategies that improve job support and feelings of
      control at work may be especially helpful to prevent poor work functioning in
      this at-risk group of employees.

PMID- 22862912
TI  - Psychotic-like or unusual subjective experiences? The role of certainty in the
      appraisal of the subclinical psychotic phenotype.
AB  - The multi-dimensional features of Unusual Subjective Experiences (USEs) may be
      more accurate indicators of psychosis-proneness than simple frequency count. We
      tested whether subjective certainty or uncertainty of the occurrence of USEs can
      influence perceived wellbeing. Five hundred and four undergraduate students
      completed measures of delusion- and hallucination-proneness, general health and
      emotional processing. Participants' responses on the delusion- and hallucination
      proneness scales were dichotomized on the basis of their certainty level. Results
      showed that, USEs rated with certainty were associated with poor self-perceived
      health and difficult emotional processing, while those rated with uncertainty
      were not. Certainty of USEs was associated with increased distress and may be
      important in characterizing psychopathological significance. Specific
      characteristics associated with USEs may be more important than their frequency
      in predicting psychosis risk.

PMID- 22862913
TI  - Overexpression of NRPS4 leads to increased surface hydrophobicity in Fusarium
      graminearum.
AB  - The plant pathogen Fusarium graminearum is the infamous cause of Fusarium head
      blight worldwide resulting in significant losses of yield and reduced grain feed
      quality. It also has the potential to produce a range of small bioactive peptides
      produced by the non ribosomal peptide synthetases (NRPSs). Most of these are
      unknown as F. graminearum contains 19 NRPS encoding genes, but only three have
      been assigned products. For the first time, we use deletion and overexpression
      mutants to investigate the functions and product of NRPS4 in F. graminearum.
      Deletion of NRPS4 homologues in Alternaria brassicicola and Cochloibolus
      heterostrophus has been shown to result in mutants unable to repel water. In a
      time study of surface hydrophobicity we observed that water droplets could
      penetrate 7 d old colonies of the NRPS4 deletion mutants. Loss in ability to
      repel water was first observed on 13 d old cultures of the wild type strain,
      whereas the overexpression strain remained water repellant throughout the 38 d
      time study. The conidia of both mutants were examined and those of the
      overexpression mutant showed distinct morphological differences in form of
      collapsed cells. These observations might suggest that the peptide product of
      NRPS4 could be an architectural factor in the cell walls of Fusarium or an
      indirect regulator of hydrophobicity.

PMID- 22862914
TI  - Purification, characterization and decolorization of bilirubin oxidase from
      Myrothecium verrucaria 3.2190.
AB  - Myrothecium verrucaria 3.2190 is a nonligninolytic fungus that produces bilirubin
      oxidase. Both M. verrucaria and the extracellular bilirubin oxidase were tested
      for their ability to decolorize indigo carmine. The biosorption and
      biodegradation of the dye were detected during the process of decolorization;
      more than 98% decolorization efficiency was achieved after 7 days at 26 degrees
      C. Additionally, the crude bilirubin oxidase can efficiently decolorize indigo
      carmine at 30 degrees C~50 degrees C, pH 5.5~9.5 with dye concentrations of 50 mg
      l(-1)~200 mg l(-1). Bilirubin oxidase was purified and visualized as a single
      band on native polyacrylamide gel electrophoresis (PAGE). Several enzymatic
      properties of the purified enzyme were investigated. Moreover, the identity of
      the purified bilirubin oxidase (BOD) was confirmed by matrix assisted laser
      desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). These
      results demonstrate that the purified bilirubin oxidase in M. verrucaria strain
      has potential application in dye effluent decolorization.

PMID- 22862915
TI  - Occurrence of two different species of mitoviruses in the European race of
      Gremmeniella abietina var. abietina, both hosted by the genetically unique
      Spanish population.
AB  - The genetic structure of the genus Mitovirus community hosted by the European
      pathogenic conifer fungus Gremmeniella abietina var. abietina was investigated.
      Gremmeniella abietina is a species complex with a divergent mycovirus community,
      composed mainly of Totivirus, Partitivirus, and Mitovirus species. In this work,
      the total doubled-stranded (ds)RNA from 353 isolates from Canada, Finland, Spain,
      Switzerland, Turkey, and USA was extracted to look for the presence of a ca. 2.5
      kb band typical of mitoviruses' genomes. Based on the banding data, 60 partial
      RNA-dependent RNA polymerase (RdRp) DNA sequences (ca. 500 bp) were amplified
      with reverse transcription-polymerase chain reaction (RT-PCR) and sequenced. Two
      distantly related mitovirus groups (species) were observed in the clustering
      analysis, one of them related to GMV1-1 and the other one related to a new
      putative species described in this study, GMV2-1. Viruses in these two clusters
      seemed to be subjected to purifying selection. The cluster with GMV1-1 included
      viruses observed in the Finnish biotype A and Spanish strains, whereas the
      cluster including GMV2-1 was composed of viruses of the Finnish biotype B and one
      from the Spanish population. Thereby, the Spanish population of G. abietina
      harboured mitovirus strains occurring in both biotype A and B strains, and it is
      the first one hosting distantly related mycoviruses of a single genus in one
      population of G. abietina. This may suggest that horizontal transmission of
      viruses could have occurred between biotype B and the Spanish population.

PMID- 22862916
TI  - Immobilized laccase of Cerrena unicolor for elimination of endocrine disruptor
      micropollutants.
AB  - The white-rot fungus Cerrena unicolor C-139 produced 450 000 U l(-1) of laccase
      when cultivated in submerged (50 ml) fermentation of wheat bran. Laccase
      (benzenediol: oxygen oxidoreductase, EC 1.10.3.2.), from C. unicolor C-139 was
      immobilized covalently on control porosity carrier silica beads. The activity of
      the immobilized laccase was approximately 15.8 units per gram of silica beads.
      The pH optimum was between 2.5 and 3.0 for free and immobilized laccase. The
      immobilization of enzyme appeared to be the main factor for retention of laccase
      activity at high temperature of 80  degrees C. The apparent K(m) value (100
      MUmol) of immobilized laccase from C. unicolor C-139 was 6.7 times higher than
      free laccase (15 MUmol) using 2,2-azino-bis-[3-ethylthiazoline-6-sulfonate]
      (ABTS) as the substrate. Immobilized laccase was able to eliminate 80 % of
      Bisphenol A, 40 % of Nonylphenol, and 60 % of Triclosan from solutions containing
      50 MUmol of each micropollutant separately. The experiments were run three times
      consecutively with the same immobilized laccase without loss of enzyme activity.

PMID- 22862917
TI  - Appressorium morphogenesis and cell cycle progression are linked in the grass
      powdery mildew fungus Blumeria graminis.
AB  - Conidial germination and differentiation - the so-called prepenetration processes
      - of the barley powdery mildew fungus (Blumeria graminis f. sp. hordei) are
      essential prerequisites for facilitating penetration of the host cuticle.
      Although the cell cycle is known to be pivotal to cellular differentiation in
      several phytopathogenic fungi there is as yet no information available concerning
      the relationship between cell cycle and infection structure development in the
      obligate biotroph B. graminis. The timing of specific developmental events with
      respect to nuclear division and morphogenesis was followed on artificial and host
      leaf surfaces by 4',6-diamidino-2-phenylindole (DAPI) staining in combination
      with a pharmacological approach applying specific cell cycle inhibitors. It was
      found that the uninucleate conidia germinated and then underwent a single round
      of mitosis 5-6 h after inoculation. During primary germ tube formation the
      nucleus frequently migrated close to the site of primary germ tube emergence.
      This nuclear repositioning was distinctly promoted by very-long-chain aldehydes
      that are common host cuticular wax constituents known to induce conidial
      differentiation. The subsequent morphogenesis of the appressorial germ tube
      preceded mitosis that was spatially uncoupled from subsequent cytokinesis.
      Blocking of S-phase with hydroxyurea did not inhibit formation of the
      appressorial germ tube but prevented cytokinesis and appressorium maturation.
      Benomyl treatment that arrests the cell cycle in mitosis inhibited nuclear
      separation, cytokinesis, and formation of mature appressoria. Thus, we conclude
      that a completed mitosis is not a prerequisite for the formation and swelling of
      the appressorial germ tube, which normally provides the destination for one of
      the daughter nuclei, while appressorium maturation depends on mitosis.

PMID- 22862918
TI  - Potential role for saccharopine reductase in swainsonine metabolism in endophytic
      fungus, Undifilum oxytropis.
AB  - Locoweed plants in the southwestern United States often harbour a slow-growing
      endophytic fungus, Undifilum oxytropis (Phylum: Ascomycota; Order: Pleosporales),
      which produces a toxic alkaloid, swainsonine. Consumption of U. oxytropis by
      grazing animals induces a neurological disorder called locoism for which the
      toxic alkaloid swainsonine has been reported to be the causal agent. Little is
      known about the biosynthetic pathway of swainsonine in endophytic fungi, but
      previous studies on non-endophytic ascomycetous fungi indicate that pipecolic
      acid and saccharopine are key intermediates. We have used degenerate primers,
      Rapid amplification of cDNA ends (RACE)-PCR and inverse PCR to identify the gene
      sequence of U. oxytropis saccharopine reductase. To investigate the role of this
      gene product in swainsonine metabolism, we have developed a gene deletion system
      for this slow-growing endophyte based on our recently established transformation
      protocol. A strain of U. oxytropis lacking saccharopine reductase had decreased
      levels of saccharopine and lysine along with increased accumulation of pipecolic
      acid and swainsonine. Thus, saccharopine reductase influences the accumulation of
      swainsonine and its precursor, pipecolic acid, in U. oxytropis.

PMID- 22862919
TI  - Isolation and functional characterization of Sporothrix schenckii ROT2, the
      encoding gene for the endoplasmic reticulum glucosidase II.
AB  - The N-linked glycosylation is a ubiquitous protein modification in eukaryotic
      cells. During the N-linked glycan synthesis, the precursor Glc(3)Man(9)GlcNAc(2)
      is processed by endoplasmic reticulum (ER) glucosidases I, II and alpha1,2
      mannosidase, before transporting to the Golgi complex for further structure
      modifications. In fungi of medical relevance, as Candida albicans and
      Aspergillus, it is well known that ER glycosidases are important for cell
      fitness, cell wall organization, virulence, and interaction with the immune
      system. Despite this, little is known about these enzymes in Sporothrix
      schenckii, the causative agent of human sporotrichosis. This limited knowledge is
      due in part to the lack of a genome sequence of this organism. In this work we
      used degenerate primers and inverse PCR approaches to isolate the open reading
      frame of S. schenckii ROT2, the encoding gene for alpha subunit of ER glucosidase
      II. This S. schenckii gene complemented a Saccharomyces cerevisiae rot2Delta
      mutant; however, when expressed in a C. albicans rot2Delta mutant, S. schenckii
      Rot2 partially increased the levels of alpha-glucosidase activity, but failed to
      restore the N-linked glycosylation defect associated to the mutation. To our
      knowledge, this is the first report where a gene involved in protein N-linked
      glycosylation is isolated from S. schenckii.

PMID- 22862920
TI  - In vivo conformation and replication intermediates of circular mitochondrial
      plasmids in Neurospora and Cryphonectria parasitica.
AB  - The in vivo conformation and replication intermediates of fungal circular
      mitochondrial plasmids and plasmid-like mitochondrial element (plMEs) were
      analyzed by two-dimensional gel electrophoresis and electron microscopy. Plasmids
      with circular restriction maps exist predominantly as circular molecules and were
      found to replicate by rolling circle mechanisms. However, the reverse
      transcriptase-encoding Mauriceville plasmid of Neurospora crassa was observed to
      replicate by two possible mechanisms: one that is consistent with a reverse
      transcriptase-mediated process and a second one might involve rolling circle DNA
      replication. Like the mtDNA-derived plasmid-like elements of N. crassa (Hausner
      et al. 2006a, b), a plasmid-like element of Cryphonectria parasitica (plME-C9),
      which consists predominantly of a 1.4 kb nucleotide sequence different from
      mitochondrial DNA, also was found to replicate by a rolling circle mechanism.
      Although the techniques used in this study were not suited for the establishment
      of the in vivo conformation and mode of replication of the mtDNAs of Neurospora
      or Cryphonectria, we surmise that the rolling circle mechanism might be the
      predominant mode of DNA replication in fungal mitochondria.

PMID- 22862921
TI  - Alteration of protein patterns in black rock inhabiting fungi as a response to
      different temperatures.
AB  - Rock inhabiting fungi are among the most stress tolerant organisms on Earth. They
      are able to cope with different stressors determined by the typical conditions of
      bare rocks in hot and cold extreme environments. In this study first results of a
      system biological approach based on two-dimensional protein profiles are
      presented. Protein patterns of extremotolerant black fungi -Coniosporium
      perforans, Exophiala jeanselmei - and of the extremophilic fungus 
      Friedmanniomyces endolithicus - were compared with the cosmopolitan and
      mesophilic hyphomycete Penicillium chrysogenum in order to follow and determine
      changes in the expression pattern under different temperatures. The 2D protein
      gels indicated a temperature dependent qualitative change in all the tested
      strains. Whereas the reference strain P. chrysogenum expressed the highest number
      of proteins at 40  degrees C, thus exhibiting real signs of temperature induced
      reaction, black fungi, when exposed to temperatures far above their growth
      optimum, decreased the number of proteins indicating a down-regulation of their
      metabolism. Temperature of 1  degrees C led to an increased number of proteins in
      all of the analysed strains, with the exception of P. chrysogenum. These first
      results on temperature dependent reactions in rock inhabiting black fungi
      indicate a rather different strategy to cope with non-optimal temperature than in
      the mesophilic hyphomycete P. chrysogenum.

PMID- 22862922
TI  - Quorum sensing in the probiotic bacterium Escherichia coli Nissle 1917 (Mutaflor)
      - evidence that furanosyl borate diester (AI-2) is influencing the cytokine
      expression in the DSS colitis mouse model.
AB  - BACKGROUND: "Quorum sensing" (QS) is the phenomenon which allows single bacterial
      cells to measure the concentration of bacterial signal molecules. Two principle
      different QS systems are known, the Autoinducer 1 system (AI-1) for the
      intraspecies communication using different Acyl-homoserine lactones (AHL) and AI
      2 for the interspecies communication. Aim of this study was to investigate QS of
      Escherichia coli Nissle 1917 (Mutaflor). RESULTS: While E. coli Nissle is
      producing AI-2 in a density dependent manner, no AI-1 was produced. To study the
      effect of AI-2 in the DSS (dextran sulphate sodium) induced mouse model of acute
      colitis, we silenced the corresponding gene luxS by intron insertion. The mutant
      bacterium E. coli Nissle::luxS was equally effective in colonizing the colon and
      the mutation turned out to be 100% stable during the course of the experiment.
      Isolating RNA from the colon mucosa and performing semiquantitative RT PCR, we
      were able to show that the expression of the pro-inflammatory cytokine IFN-y was
      suppressed in mice being infected with the E. coli Nissle wild type. Mice
      infected with the E. coli Nissle::luxS mutant showed a suppressed expression of
      IL-10 compared to uninfected mice, while the expression of the pro-inflammatory
      cytokines IL-6 and TNF-alpha was higher in these mice. The expression of mBD-1
      was suppressed in mice being infected with the mutant in comparison to the mice
      not infected or infected with the wild type. No differences were seen in the
      histological examination of the colon sections in the different groups of mice.
      CONCLUSIONS: E. coli Nissle is producing AI-2 molecules, which are influencing
      the expression of cytokines in the mucosa of the colon in the DSS mice. However,
      if QS has a direct influence on the probiotic properties of E. coli Nissle
      remains to be elucidated.

PMID- 22862923
TI  - The genetic contribution of HLA-DRB5*01:01 to systemic lupus erythematosus in
      Thailand.
AB  - Human leucocyte antigen (HLA) study in patients with systemic lupus erythematosus
      (SLE) has been investigated in various countries, but the results are still
      inconclusive. This study was performed to investigate the association between HLA
      DR and SLE in patients in northern Thailand. HLA-DR subtyping was performed in 70
      patients with SLE and 99 normal healthy controls living in northern Thailand
      using the INNO-LiPA HLA-DR Decoder kit (Innogenetics) and MICRO SSP HLA DNA
      Typing kit (One Lambda) for reconfirmation. The allele frequency (AF) of
      DRB5*01:01 in SLE was significantly higher than in the controls [25.7% vs. 14.6%,
      P = 0.012, Pc = 0.048, OR = 2.02 (95%CI = 1.17-3.48)]. The AF of DRB1*15:01 and
      DRB1*16:02 showed a nonsignificant tendency to be higher in SLE (10.7% vs. 8.1%,
      and 17.9% vs. 11.1%). Interestingly, the DRB5*01:01 allele linked to DRB1*16:02
      in 47.2% of SLE and 37.9% of controls, and the prevalence of the DRB1*16:02
      DRB5*01:01 haplotype was higher in the patients with SLE [12.1% vs. 5.6%, P =
      0.044, OR = 2.35 (95%CI = 1.06-5.19)]. The DRB1*16:02 linked to DRB5*02:02 and
      *02:03 in 18.2% and 31.8% of controls, respectively, and linked to DRB5*02:03 in
      32.0% of SLE patients. The frequency of DRB1*03:01 and *15:02 alleles was not
      increased in Thai SLE. There was no significant association between DRB5*01:01
      and any auto-antibodies or clinical manifestations of SLE. DRB5*01:01 is
      associated with Thai SLE, and the association is stronger than that of
      DRB1*15:01. The genetic contribution of DRB5*01:01 is due partially to the
      linkage disequilibrium between DRB1*16:02 and DRB5*01:01 in the northern Thai
      population.

PMID- 22862924
TI  - General practitioner provision of preventive child health care: analysis of
      routine consultation data.
AB  - BACKGROUND: GPs contribute to preventive child health care in various ways,
      including provision of child health surveillance (CHS) reviews, opportunistic
      preventive care, and more intensive support to vulnerable children. The number of
      CHS reviews offered in Scotland was reduced from 2005. This study aimed to
      quantify GPs' provision of different types of preventive care to pre-school
      children before and after the changes to the CHS system. METHODS: GP consultation
      rates with children aged 0-4 years were examined for the 21/2 years before and
      after the changes to the CHS system using routinely available data from 30
      practices in Scotland. Consultations for CHS reviews; other aspects of preventive
      care; and all reasons were considered. RESULTS: Prior to the changes to the CHS
      system, GPs often contributed to CHS reviews at 6-8 weeks and 8-9 and 39-42
      months. Following the changes, GP provision of the 6-8 week review continued but
      other reviews essentially ceased. Few additional consultations with pre-school
      children are recorded as involving other aspects of preventive care, and the
      changes to CHS have had no impact on this. In the 21/2 years before and after the
      changes, consultations recorded as involving any form of preventive care
      accounted for 11% and 7.5% respectively of all consultations with children aged 0
      4 years, with the decline due to reductions in CHS reviews. CONCLUSIONS:
      Effective preventive care through the early years can help children secure good
      health and developmental outcomes. GPs are well placed to contribute to the
      provision of such care. Consultations focused on preventive care form a small
      minority of GPs' contacts with pre-school children, however, particularly since
      the reduction in the number of CHS reviews.

PMID- 22862925
TI  - 19F MRI tracer preserves in vitro and in vivo properties of hematopoietic stem
      cells.
AB  - Hematopoietic stem cells (HSCs) have numerous therapeutic applications including
      immune reconstitution, enzyme replacement, regenerative medicine, and
      immunomodulation. The trafficking and persistence of these cells after
      administration is a fundamental question for future therapeutic applications of
      HSCs. Here, we describe the safe and efficacious labeling of human CD34(+) HSCs
      with a novel, self-delivering perfluorocarbon 19F magnetic resonance imaging
      (MRI) tracer, which has recently been authorized for use in a clinical trial to
      track therapeutic cells. While various imaging contrast agents have been used to
      track cellular therapeutics, the impact of this MRI tracer on HSC function has
      not previously been studied. Both human CD34(+) and murine bone marrow (BM) HSCs
      were effectively labeled with the MRI tracer, with only a slight reduction in
      viability, relative to mock-labeled cells. In a pilot study, 19F MRI enabled the
      rapid evaluation of HSC delivery/retention following administration into a rat
      thigh muscle, revealing the dispersal of HSCs after injection, but not after
      surgical implantation. To investigate effects on cell functionality, labeled and
      unlabeled human HSCs were tested in in vitro colony forming unit (CFU) assays,
      which resulted in equal numbers of total CFU as well as individual CFU types,
      indicating that labeling did not alter multipotency. Cobblestone assay forming
      cell precursor frequency was also unaffected, providing additional evidence that
      stem cell function was preserved after labeling. In vivo tests of multipotency
      and reconstitution studies in mice with murine BM containing labeled HSCs
      resulted in normal development of CFU in the spleen, compared to unlabeled cells,
      and reconstitution of both lymphoid and myeloid compartments. The lack of
      interference in these complex biological processes provides strong evidence that
      the function and therapeutic potential of the HSCs are likely maintained after
      labeling. These data support the safety and efficacy of the MRI tracer for
      clinical tracking of human stem cells.

PMID- 22862926
TI  - Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of
      the TCF7L2 rs7903146 risk T allele.
AB  - We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T
      risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to
      secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide
      (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and
      endogenous glucose production. All participants had a 3-h oral glucose tolerance
      test (OGTT), an intravenous glucose tolerance test and a euglycaemic,
      hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers
      had higher haemoglobin A1c levels (p = 0.030), reduced first-phase insulin
      response (p = 0.048), higher peripheral insulin sensitivity (p = 0.050) and lower
      fasting GIP concentrations (p = 0.003) than CC allele carriers. The latter was
      also reflected by lower total GIP secretion during the OGTT (p = 0.018). We found
      no significant differences in endogenous glucose production, hepatic insulin
      sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1
      between the groups. The findings suggest that the effect of TCF7L2 on diabetes
      risk may include reduced secretion of GIP.

PMID- 22862927
TI  - Sulfated cholecystokinin-8 increases ghrelin secretion but does not affect
      oxyntomodulin in Holstein steers.
AB  - The effect of appetite regulatory hormone cholecystokinin (CCK) on the secretions
      of oxyntomodulin (OXM) and ghrelin, and the effect of ghrelin on the secretions
      of CCK and OXM were studied in ruminants. Eight Holstein steers, 7 months old,
      243 +/- 7 kg body weight (BW), were arranged in an incomplete Latin square design
      (8 animals * 4 treatments * 4 days of sampling). Steers were intravenously
      injected with 10 ug of sulfated CCK-8/kg BW, 20 ug of acyl ghrelin/kg BW, 100 ug
      of des-acyl ghrelin/kg BW or vehicle. Blood samples were collected from -60 min
      to 120 min relative to time of injection. Plasma concentrations of ghrelin,
      sulfated CCK and OXM were measured by double-antibody radioimmunoassay. Plasma
      acyl ghrelin was increased to peak level (428.3 +/- 6 pg/mL) at 60 min after
      injection of CCK compared with pre-injected levels (203.3 +/- 1 pg/mL). These
      results showed for the first time, that intravenous bolus injection of CCK
      increased ghrelin secretion in ruminants. In contrast, injection of ghrelin did
      not change CCK secretion. Administration of ghrelin or CCK has no effect on
      plasma OXM concentrations. In conclusion, our results show that administration of
      CCK increased ghrelin secretion but did not affect OXM release in ruminants.
      Ghrelin did not affect the secretions of CCK and OXM.

PMID- 22862928
TI  - Effect of replacing corn with brown rice in a total, mixed, ration silage on milk
      production, ruminal fermentation and nitrogen balance in lactating dairy cows.
AB  - Nine multiparous Holstein cows were used in a replicated 3 * 3 Latin square
      design to determine the effects of substituting corn grain with brown rice (BR)
      grain in total mixed ration (TMR) silage on milk yield, ruminal fermentation and
      nitrogen (N) balance. The TMR silages were made from the ensiling of TMR
      containing (dry matter basis) 50.1% forage in rice silage and corn silage
      combination, and 49.9% concentrate. The grain portion of the diets contained
      31.2% steam-flaked corn, 31.2% steam-flaked BR or an equal mixture of corn and
      BR. Dietary treatments did not affect dry matter intake, milk yield and milk fat,
      protein and lactose yields. The ruminal pH and total volatile fatty acid
      concentrations were not affected by dietary treatment. The urinary N excretion
      decreased linearly (P < 0.01) in response to increased levels of BR, with no
      dietary effect on N intake, N secretion in milk and fecal N excretion. Our
      results indicate that steam-flaked BR is a suitable replacement for steam-flaked
      corn in dairy cow diets, and that it can be included in rations to a level of at
      least 31.2% of dry matter without adverse effects on milk production, when cows
      were fed rice silage and corn silage-based diets.

PMID- 22862929
TI  - Feeding Aspergillus awamori reduces skeletal muscle protein breakdown and
      stimulates growth in broilers.
AB  - This study was conducted to show that dietary supplementation of a fungus,
      Aspergillus awamori called Koji in Japan, reduces skeletal muscle protein
      breakdown and stimulates growth in broiler chickens. A total of 30 chicks at 15
      days of age was divided into control and two treatment groups (10 birds per
      treatment). Control group was fed basal diet and treatment groups were fed the
      basal diets supplemented with A. awamori at levels of 0.05% and 0.2%. The birds
      were raised for 12 days from 15 to 27 days of age and then the effect on growth,
      organ weights and plasma 3-methylhistidine concentration and digestibilities of
      protein and energy was evaluated. The messenger RNAs (mRNAs) of atrogin-1,
      ubiquitin, proteasome, m-calpain, u-calpain, beta-actin, myosin and pax-7 in the
      breast muscle were also measured. Body weight gain and breast muscle weight were
      increased, although feed intake was decreased by the fungus and thus feed
      efficiency was increased. Protein and energy digestibilities were increased.
      Furthermore, plasma 3-methylhistidine concentration was decreased by the fungus.
      The mRNAs of atrogin-1, ubiquitin, proteasome, m-calpain and u-calpain were all
      decreased. The mRNA of beta-actin but not myosin and pax-7 was slightly increased
      by the fungus. In conclusion, feeding A. awamori improves growth performance
      because skeletal muscle proteolytic activity is reduced and digestibilities of
      energy and protein are increased.

PMID- 22862930
TI  - Effect of dietary turmeric on antioxidant properties of thigh meat in broiler
      chickens after slaughter.
AB  - Two hundred and fifty-day-old male broiler chicks (Ross 308) were used to
      investigate the dietary supplementation effects of different levels of 0.0
      turmeric rhizome powder (TRP) (free TRP, F.TRP), 0.25 (low TRP, L.TRP), 0.5
      (medium TRP, M.TRP) and 0.75% TRP (high TRP, H.TRP) or 50 mg/kg vitamin E (VE) on
      antioxidant properties of thigh meat in broiler chickens after slaughter. No
      effect of treatment was observed for the activities of glutathione peroxidase
      (GPX) and superoxide dismutase (SOD) and total antioxidant status (TAS) in thigh
      meat (P > 0.05) but all were reduced over time (P < 0.0001). A significant
      treatment*time interaction was observed for thigh meat GPX activity (P = 0.02).
      Significant effects of treatment and time were observed for malondialdehyde (MDA)
      content (P < 0.05). There was no significant difference between the treatments
      for thigh meat MDA content at slaughter (P > 0.05). Three days after refrigerator
      storage, MDA content in thigh meat of M.TRP birds was lower than that of F.TRP
      birds (P < 0.05). Both the M.TRP and VE birds showed a lower MDA content in thigh
      meat as compared with F.TRP birds 7 days after storage (P < 0.05). In conclusion,
      dietary consumption of 5 mg/kg TRP can increases the thigh meat shelf-life
      storage and quality in broiler chickens after slaughter.

PMID- 22862931
TI  - Utilization of dietary urea nitrogen is stimulated by D-mannitol feeding in
      rabbits.
AB  - The effect of D-mannitol as an indigestible sugar on apparent digestibility of
      nutrients, nitrogen (N) utilization and growth performance, have been
      investigated in growing rabbits fed a urea-containing diet. In experiment 1, 40
      day-old male rabbits were fed a commercial diet with urea 10 g/kg with added
      glucose or D-mannitol 60 g/kg each. Thereafter, in experiment 2 the rabbits aged
      55 days were fed a commercial diet with or without urea 10 g/kg. Feed restriction
      at 55 g/kg(0.75)/day was carried out in both experiments. Addition of D-mannitol
      to the urea-containing diet decreased urinary N excretion, which consequently
      increased N retention and ratios of retained N to consumed N or apparently
      absorbed N. Addition of urea alone to the diet increased daily N intake and
      urinary N excretion but did not affect N retention. Weight gain and feed
      efficiency were improved by D-mannitol feeding, whereas feeding with urea alone
      did not affect these parameters. Utilization of dietary urea was enhanced in
      growing rabbits fed the urea-containing diet with D-mannitol, resulting in
      improvement of N retention and growth performance.

PMID- 22862932
TI  - Effects of photoperiod on the secretion of growth hormone in female goats.
AB  - The aim of the present study was to clarify the effect of photoperiod on the
      secretion of growth hormone (GH) in goats. Adult female goats were kept at 20
      degrees C with an 8-h or 16-h photoperiod, and secretory patterns of GH for 4 h
      (12.00 to 16.00 hours) were compared. In addition, the goats were kept under a 16
      h photoperiod and orally administered saline (controls) or melatonin, and the
      effects of melatonin on the secretion of GH were examined. GH was secreted in a
      pulsatile manner. There were no significant differences in pulse frequency
      between the 8- and 16-h photoperiods; however, GH pulse amplitude tended to be
      greater in the group with the 16-h photoperiod (P = 0.1), and mean GH
      concentrations were significantly greater in the 16-h photoperiod (P < 0.05). The
      GH-releasing response to GH-releasing hormone (GHRH) was also significantly
      greater for the 16-h photoperiod (P < 0.05). There were no significant
      differences in GH pulse frequency between the saline- and melatonin-treated
      groups. However, GH pulse amplitude and mean GH concentrations were significantly
      greater in the saline-treated group (P < 0.05). The present results show that a
      long photoperiod enhances the secretion of GH, and melatonin modifies GH
      secretion in female goats.

PMID- 22862933
TI  - Stable fighting strategies to maintain social ranks in captive male Alpine musk
      deer (Moschus sifanicus).
AB  - This study was conducted at the XINGLONGSHAN Musk Deer Farm of China from July to
      September 2008. Results showed that captive male musk deer exhibit aggressive
      dominance behavior, by which a stable social ranking is established. Generally,
      there were three types of aggression in agonistic interactions among males:
      attacking, displacing and threatening. Threatening was more frequently observed
      than displacing and attacking. When in conflict with other deer, high-rank males
      exhibited significantly more attacking than displacing and threatening. Moreover,
      no attacking occurred in low-rank and middle-rank males, but these individuals
      initiated significantly more threatening displays than high-rank individuals.
      Among musk deer groups with different social ranks, there were no significant
      differences between threats received by middle-rank and low-rank groups, but
      attacks directed to high-rank males was significantly lower than displacing and
      threatening behaviors. On the basis of these results, it is suggested that when a
      captive male musk deer population is assembled, individuals should be diversified
      in fighting ability and level of aggression. In particular, deer with higher
      aggression should not be enclosed with deer with similar tendencies, but should
      be enclosed with individuals with lower fighting levels. This should maintain
      stable social structures within captive musk deer groups and improve the overall
      welfare of captive musk deer.

PMID- 22862934
TI  - Genetic background affects induced pluripotent stem cell generation.
AB  - INTRODUCTION: The influence of genetic background on the ability to generate
      induced pluripotent stem cells (iPSCs) has the potential to impact future
      applications, but has yet to be examined in detail. The purpose of this study was
      to determine if genetic background affects the efficiency of generating iPSCs
      during early reprograming as well as the pluripotent stability of the iPSCs
      during later stages of reprograming. METHODS: Mouse embryonic fibroblasts (MEFs)
      were isolated from six strains of mice (NON/LtJ; C57BL/6J; DBA/2J; BALB/cJ;
      129S1/SvlmJ; CAST/EiJ) that were selected based on genetic diversity and
      differences in ability to produce embryonic stem cell (ESC) lines. MEFs were
      reprogramed via doxycycline-inducible lentiviral transduction of murine Oct4,
      Klf4, Sox2, and c-Myc. Differences in efficiency to generate iPSCs were assessed
      by comparing the total number of colonies, the percentage of colonies positive
      for alkaline phosphatase staining and the percentage of cells positive for SSEA1.
      iPSC colonies were expanded to establish doxycycline-independent cell lines whose
      pluripotency was then evaluated via ability to form teratomas in NOD.CB17
      Prkdcscid/J mice. Proliferation of non-transduced parent MEFs from each strain
      was also examined over ten days under conditions that simulated reprograming.
      RESULTS: NON/LtJ and CAST/EiJ strains were more efficient than other strains in
      generating iPSCs for all parameters measured and parent MEFs from these strains
      were more proliferative than those from other strains. Doxycycline-independent
      iPSC lines were established using standard conditions for all strains except
      BALB/cJ, which required a higher concentration (5x) of leukemia inhibitory factor
      (LIF). iPSCs from all strains were capable of producing teratomas in NOD.CB17
      Prkdcscid/J mice. CONCLUSIONS: The results of this study suggest that genetic
      background does affect iPSC generation and pluripotent stability. In addition,
      our results demonstrate that strain differences in efficiency to generate iPSCs
      during the early stages of reprograming are correlated with those observed in
      proliferation of parent MEFs. These findings have important implications both for
      future iPSC applications as well as for future investigation into determining the
      genes responsible for reprograming efficiency and stability.

PMID- 22862935
TI  - Decision boxes for clinicians to support evidence-based practice and shared
      decision making: the user experience.
AB  - BACKGROUND: This project engages patients and physicians in the development of
      Decision Boxes, short clinical topic summaries covering medical questions that
      have no single best answer. Decision Boxes aim to prepare the clinician to
      communicate the risks and benefits of the available options to the patient so
      they can make an informed decision together. METHODS: Seven researchers
      (including four practicing family physicians) selected 10 clinical topics
      relevant to primary care practice through a Delphi survey. We then developed two
      one-page prototypes on two of these topics: prostate cancer screening with the
      prostate-specific antigen test, and prenatal screening for trisomy 21 with the
      serum integrated test. We presented the prototypes to purposeful samples of
      family physicians distributed in two focus groups, and patients distributed in
      four focus groups. We used the User Experience Honeycomb to explore barriers and
      facilitators to the communication design used in Decision Boxes. All discussions
      were transcribed, and three researchers proceeded to thematic content analysis of
      the transcriptions. The coding scheme was first developed from the Honeycomb's
      seven themes (valuable, usable, credible, useful, desirable, accessible, and
      findable), and included new themes suggested by the data. Prototypes were
      modified in light of our findings. RESULTS: Three rounds were necessary for a
      majority of researchers to select 10 clinical topics. Fifteen physicians and 33
      patients participated in the focus groups. Following analyses, three sections
      were added to the Decision Boxes: introduction, patient counseling, and
      references. The information was spread to two pages to try to make the Decision
      Boxes less busy and improve users' first impression. To try to improve
      credibility, we gave more visibility to the research institutions involved in
      development. A statement on the boxes' purpose and a flow chart representing the
      shared decision-making process were added with the intent of clarifying the
      tool's purpose. Information about the risks and benefits according to risk levels
      was added to the Decision Boxes, to try to ease the adaptation of the information
      to individual patients. CONCLUSION: Results will guide the development of the
      eight remaining Decision Boxes. A future study will evaluate the effect of
      Decision Boxes on the integration of evidence-based and shared decision making
      principles in clinical practice.

PMID- 22862936
TI  - Adult neurogenesis: VCAM stems the tide.
AB  - In this issue of Cell Stem Cell, Kokovay et al. uncover that VCAM1 expression in
      neural stem cells regulates adult neurogenesis. Cerebrospinal fluid-borne IL
      1beta upregulates VCAM1 expression, which in turn regulates the architecture of
      the stem cell niche, redox homeostasis, and neurogenesis.

PMID- 22862937
TI  - Chromatin and pluripotency: the MYSTerious connection.
AB  - Although histone acetylation is critical for maintaining embryonic stem cell
      pluripotency, the molecular machinery involved remains poorly understood. Li et
      al. (2012) now show that Mof, a MYST family histone acetyltransferase, functions
      as a coactivator of Nanog-mediated transcription, maintains the expression of
      pluripotency-associated genes, and primes developmental genes for
      differentiation.

PMID- 22862938
TI  - Reporting live from the epidermal stem cell compartment!
AB  - Hair follicle regeneration is controlled by an intricate relationship between
      epidermal stem cells and their microenvironment. A recent report in Nature by
      Rompolas et al. (2012) uses two-photon live imaging to interrogate the spatial
      organization and cellular requirements for hair follicle regeneration by
      epidermal stem cells and their immediate progeny.

PMID- 22862939
TI  - Greasing the way: the ABCs of HSPC efflux from the marrow.
AB  - In this issue of Cell Stem Cell, Westerterp et al. demonstrate that cholesterol
      flux through splenic phagocytes regulates hematopoietic stem and multipotential
      progenitor cell mobilization from the bone marrow. These exciting findings
      suggest new avenues for therapy of myeloproliferative disorders and
      atherosclerosis.

PMID- 22862940
TI  - Stem cell opponents? Give me your best shot.

PMID- 22862941
TI  - Generating an iPSC bank for HLA-matched tissue transplantation based on known
      donor and recipient HLA types.
AB  - The likelihood for immunological rejection of Human Leukocyte Antigens (HLA)
      mismatched induced pluripotent stem cells (iPSCs) limits their therapeutic
      potential. Here we show how a tissue bank from 150 selected homozygous HLA-typed
      volunteers could match 93% of the UK population with a minimal requirement for
      immunosuppression. Our model provides a practical approach for using existing HLA
      typed samples to generate an iPSC stem cell bank that circumvents prospective
      typing of a large number of individuals.

PMID- 22862942
TI  - How can human pluripotent stem cells help decipher and cure Huntington's disease?
AB  - Pluripotent stem cell (PSC) technologies are becoming a key asset for deciphering
      pathological cascades and for developing new treatments against many
      neurodegenerative disorders, including Huntington's disease (HD). This
      perspective discusses the challenges and opportunities facing the use of PSCs for
      treating HD, focusing on four major applications: namely, the use of PSCs as a
      substitute source of human striatal cells for current HD cell therapy, as a
      cellular model of HD for the validation of human-specific gene therapies, for
      deciphering molecular mechanisms underlying HD, and in drug discovery.

PMID- 22862943
TI  - The histone acetyltransferase MOF is a key regulator of the embryonic stem cell
      core transcriptional network.
AB  - Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential
      for rapid response to differentiation cues. Both ESC features are subject to
      epigenetic regulation. Here we show that the histone acetyltransferase Mof plays
      an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs
      with Mof deletion lose characteristic morphology, alkaline phosphatase (AP)
      staining, and differentiation potential. They also have aberrant expression of
      the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes
      of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting
      the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome
      wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is
      an integral component of the ESC core transcriptional network and that Mof primes
      genes for diverse developmental programs. Mof is also required for Wdr5
      recruitment and H3K4 methylation at key regulatory loci, highlighting the
      complexity and interconnectivity of various chromatin regulators in ESCs.

PMID- 22862944
TI  - Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling.
AB  - Many signals must be integrated to maintain self-renewal and pluripotency in
      embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC)
      reprogramming. However, the exact molecular regulatory mechanisms remain elusive.
      To unravel the essential internal and external signals required for sustaining
      the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated
      phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka),
      resulted in compromised self-renewal and consequent differentiation. By
      integrating global gene expression and computational analyses, we discovered that
      loss of Aurka leads to upregulated p53 activity that triggers ESC
      differentiation. Specifically, Aurka regulates pluripotency through
      phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal
      gene expression. Phosphorylation of p53 not only impairs p53-induced ESC
      differentiation but also p53-mediated suppression of iPSC reprogramming. Our
      studies demonstrate an essential role for Aurka-p53 signaling in the regulation
      of self-renewal, differentiation, and somatic cell reprogramming.

PMID- 22862945
TI  - Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol
      efflux pathways.
AB  - Intact cholesterol homeostasis helps to maintain hematopoietic stem and
      multipotential progenitor cell (HSPC) quiescence. Mice with defects in
      cholesterol efflux pathways due to deficiencies of the ATP binding cassette
      transporters ABCA1 and ABCG1 displayed a dramatic increase in HSPC mobilization
      and extramedullary hematopoiesis. Increased extramedullary hematopoiesis was
      associated with elevated serum levels of G-CSF due to generation of IL-23 by
      splenic macrophages and dendritic cells. This favored hematopoietic lineage
      decisions toward granulocytes rather than macrophages in the bone marrow leading
      to impaired support for osteoblasts and decreased Cxcl12/SDF-1 production by
      mesenchymal progenitors. Greater HSPC mobilization and extramedullary
      hematopoiesis were reversed by raising HDL levels in Abca1(-/-)Abcg1(-/-) and
      Apoe(-/-) mice or in a mouse model of myeloproliferative neoplasm mediated by
      Flt3-ITD mutation. Our data identify a role of cholesterol efflux pathways in the
      control of HSPC mobilization. This may translate into therapeutic strategies for
      atherosclerosis and hematologic malignancies.

PMID- 22862946
TI  - Targeting tetramer-forming GABPbeta isoforms impairs self-renewal of
      hematopoietic and leukemic stem cells.
AB  - Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are both capable
      of self-renewal, with HSCs sustaining multiple blood lineage differentiation and
      LSCs indefinitely propagating leukemia. The GABP complex, consisting of DNA
      binding GABPalpha subunit and transactivation GABPbeta subunit, critically
      regulates HSC multipotency and self-renewal via controlling an essential gene
      regulatory module. Two GABPbeta isoforms, GABPbeta1L and GABPbeta2, contribute to
      assembly of GABPalpha(2)beta(2) tetramer. We demonstrate that GABPbeta1L/beta2
      deficiency specifically impairs HSC quiescence and survival, with little impact
      on cell cycle or apoptosis in differentiated blood cells. The HSC-specific effect
      is mechanistically ascribed to perturbed integrity of the GABP-controlled gene
      regulatory module in HSCs. Targeting GABPbeta1L/beta2 also impairs LSC self
      renewal in p210(BCR-ABL)-induced chronic myelogenous leukemia (CML) and exhibits
      synergistic effects with tyrosine kinase inhibitor imatinib therapy in inhibiting
      CML propagation. These findings identify the tetramer-forming GABPbeta isoforms
      as specific HSC regulators and potential therapeutic targets in treating LSC
      based hematological malignancy.

PMID- 22862947
TI  - VCAM1 is essential to maintain the structure of the SVZ niche and acts as an
      environmental sensor to regulate SVZ lineage progression.
AB  - Neurons arise in the adult forebrain subventricular zone (SVZ) from Type B neural
      stem cells (NSCs), raising considerable interest in the molecules that maintain
      this life-long neurogenic niche. Type B cells are anchored by specialized apical
      endfeet in the center of a pinwheel of ependymal cells. Here we show that the
      apical endfeet express high levels of the adhesion and signaling molecule
      vascular cell adhesion molecule-1 (VCAM1). Disruption of VCAM1 in vivo causes
      loss of the pinwheels, disrupted SVZ cytoarchitecture, proliferation and
      depletion of the normally quiescent apical Type B cells, and increased
      neurogenesis in the olfactory bulb, demonstrating a key role in niche structure
      and function. We show that VCAM1 signals via NOX2 production of reactive oxygen
      species (ROS) to maintain NSCs. VCAM1 on Type B cells is increased by IL-1beta,
      demonstrating that it can act as an environmental sensor, responding to
      chemokines involved in tissue repair.

PMID- 22862948
TI  - Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the proliferation of
      muscle precursor cells by an epigenetic mechanism.
AB  - In mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays
      some important yet unknown functions at the perinatal stage. To elucidate its in
      vivo functions, we initiated a yeast two-hybrid screening to look for Pax7
      interacting proteins and identified a previously uncharacterized Pax7- and Pax3
      binding protein (Pax3/7BP). Pax3/7BP is a ubiquitously expressed nuclear protein,
      enriched in Pax7+ muscle precursor cells (MPCs), and serves as an indispensable
      adaptor for Pax7 to recruit the histone 3 lysine 4 (H3K4) methyltransferase (HMT)
      complex by bridging Pax7 and Wdr5. Knockdown of Pax3/7BP abolished the Pax3/7
      associated H3K4 HMT activity and inhibited the proliferation of Pax7+ MPCs from
      young mice both in culture and in vivo. Id3 and Cdc20 were direct target genes of
      Pax7 and Pax3/7BP involved in the proliferation of Pax7+ MPCs. Collectively, our
      work establishes Pax3/7BP as an essential adaptor linking Pax3/7 with the H3K4
      HMT to regulate the proliferation of MPCs.

PMID- 22862949
TI  - Small molecule-mediated TGF-beta type II receptor degradation promotes
      cardiomyogenesis in embryonic stem cells.
AB  - The cellular signals controlling the formation of cardiomyocytes, vascular smooth
      muscle, and endothelial cells from stem cell-derived mesoderm are poorly
      understood. To identify these signals, a mouse embryonic stem cell (ESC)-based
      differentiation assay was screened against a small molecule library resulting in
      a 1,4-dihydropyridine inducer of type II TGF-beta receptor (TGFBR2) degradation-1
      (ITD-1). ITD analogs enhanced proteasomal degradation of TGFBR2, effectively
      clearing the receptor from the cell surface and selectively inhibiting
      intracellular signaling (IC(50) ~0.4-0.8 MUM). ITD-1 was used to evaluate TGF
      beta involvement in mesoderm formation and cardiopoietic differentiation, which
      occur sequentially during early development, revealing an essential role in both
      processes in ESC cultures. ITD-1 selectively enhanced the differentiation of
      uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and
      endothelial cells. ITD-1 is a highly selective TGF-beta inhibitor and reveals an
      unexpected role for TGF-beta signaling in controlling cardiomyocyte
      differentiation from multipotent cardiovascular precursors.

PMID- 22862950
TI  - Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4
      induced injuries in rats.
AB  - BACKGROUND: Launaea procumbens (Asteraceae) is used as a folk medicine to treat
      hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea
      procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver
      damage in rats. METHODS: To evaluate the hepatoprotective effects of LPCE, 36
      male Sprague-Dawley rats were equally divided into six groups. Animals of group 1
      (control) had free access to food and water. Group II received 3 ml/kg of CCl4
      (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks.
      Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of
      CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg
      b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE
      (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant
      enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase
      (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive
      substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic
      nucleolar organizer regions (AgNORs) counts and histopathology were studied in
      liver samples. Serum was analyzed for various biochemical parameters.
      Phytochemical composition in LPCE was determined through high-performance liquid
      chromatography (HPLC). RESULTS: LPCE inhibited lipid peroxidation, and reduced
      the activities of aspartate transaminase, alanine transaminase, alkaline
      phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents
      were increased as were the activities of antioxidant enzymes (catalase, SOD, GST,
      GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver
      weight, relative liver weight and the number of hepatic lesions were reduced with
      co-administration of LPCE. Phyochemical analyses of LPCE indicated that it
      contained catechin, kaempferol, rutin, hyperoside and myricetin. CONCLUSION:
      These results indicated that Launaea procumbens efficiently protected against the
      hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects
      of flavonoids present in LPCE.

PMID- 22862951
TI  - Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma
      after curative resection (EPTRH): a randomized, prospective, controlled
      multicenter trial.
AB  - BACKGROUND: Hepatic resection is currently still the best choice of therapeutic
      strategies for liver cancer, but the long-term survival rate after surgery is
      unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The
      reasons for this high recurrence rate are not entirely clear. Recent studies have
      indicated that ischemia-reperfusion injury to the liver may be a significant
      factor promoting tumor recurrence and metastasis in animal models. If this is
      also true in humans, the effects of the Pringle maneuver, which has been widely
      used in hepatectomy for the past century, should be examined. To date, there are
      no reported data or randomized controlled studies examining the relationship
      between use of the Pringle maneuver and local tumor recurrence. We hypothesize
      that the long-term prognosis of patients with liver cancer could be worsened by
      use of the Pringle maneuver due to an increase in the rate of tumor recurrence in
      the liver remnant. We designed a multicenter, prospective, randomized surgical
      trial to test this hypothesis. METHODS: At least 498 eligible patients from five
      participating centers will be enrolled and randomized into either the Pringle
      group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks
      randomization protocol. After the completion of surgical intervention, patients
      will be included in a 3-year follow-up program. DISCUSSION: This multicenter
      surgical trial will examine whether the Pringle maneuver has a negative effect on
      the long-term outcome of hepatocellular carcinoma patients. The trial will also
      provide information about prognostic differences, safety, advantages and
      disadvantages between Pringle and non-Pringle surgical procedures. Ultimately,
      the results will increase the available information about the effects of ischemia
      reperfusion injury on tumor recurrence, which will be of immense benefit to
      general surgery. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00725335.

PMID- 22862952
TI  - Multiple viral infections after haploidentical hematopoietic stem cell
      transplantation in a child with acute lymphoblastic leukemia.
AB  - After allogeneic hematopoietic stem cell transplantation (HSCT), viral
      infections/reactivations are a frequent complication, sometimes with fatal
      outcome. Thus, early diagnosis is recommended by screening of whole blood or
      plasma preparations using highly sensitive molecular techniques that test for the
      most common viral pathogens, such as Epstein-Barr virus, cytomegalovirus, and
      adenoviruses (ADVs). Despite this approach, not every reactivation/infection can
      be adequately detected or excluded, even with highly sensitive polymerase chain
      reaction. Particularly after toxic treatment, uncommon infections or infections
      resistant to first-line treatment can occur, even in unusual locations. Herein,
      we present the case of a child with Philadelphia chromosome-positive acute
      lymphoblastic leukemia after allogeneic HSCT who suffered from 5 different viral
      reactivations/infections, including acyclovir-resistant herpes simplex virus type
      1 esophagitis, human herpesvirus 6 encephalitis, rotavirus gastroenteritis,
      respiratory syncytial virus pneumonia, and ADV esophagitis, despite routinely
      performed blood examinations for viral pathogens remaining unrevealing at all
      times.

PMID- 22862953
TI  - A stereological study of the volume-weighted volume and of the relative volume of
      the nucleus of normal and preneoplastic hepatocytes in a trout model of
      hepatocarcinogenesis.
AB  - The fish liver has been the main subject of the biomonitoring and laboratory
      studies dealing with environmental carcinogenesis. The foci of cellular
      alterations are accepted pre-neoplastic hepatic lesions, and histopathology is
      the primary tool for their characterization. Despite its potential, using
      stereology to study quantitatively nuclear features of those lesions has not been
      evaluated. Herein, we estimated the volume density and the volume-weighted volume
      of the nucleus of normal and preneoplastic hepatocytes, using stereology and the
      brown trout (Salmo trutta f. fario) as model. In the hepatocarcinogenesis
      protocol the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used as initiator,
      and the 17-beta estradiol (E2) as promoter. Three groups of 30 animals were
      considered: negative controls (non-exposed), initiator exposed and initiator plus
      promoter exposed. Estimates of both stereological parameters were significantly
      higher in preneoplastic hepatocytes, also showing an excellent discriminatory
      power when used to differentiate those hepatocytes from the normal ones. Besides,
      in the normal parenchyma the two parameters also differed among the three tested
      groups. The exposure to MNNG and/or to E2 leaded to modifications in the
      hepatocyte nuclei that could be unbiasedly quantified with two stereological
      parameters. We showed that quantitative nuclear morphology represents a valuable
      auxiliary tool in assessing hepatocarcinogenesis in fishes.

PMID- 22862954
TI  - First-in-man application of a novel therapeutic cancer vaccine formulation with
      the capacity to induce multi-functional T cell responses in ovarian, breast and
      prostate cancer patients.
AB  - BACKGROUND: DepoVax is a novel non-emulsion depot-forming vaccine platform with
      the capacity to significantly enhance the immunogenicity of peptide cancer
      antigens. Naturally processed HLA-A2 restricted peptides presented by breast,
      ovarian and prostate cancer cells were used as antigens to create a therapeutic
      cancer vaccine, DPX-0907. METHODS: A phase I clinical study was designed to
      examine the safety and immune activating potential of DPX-0907 in advanced stage
      breast, ovarian and prostate cancer patients. A total of 23 late stage cancer
      patients were recruited and were divided into two dose/volume cohorts in a three
      immunization protocol. RESULTS: DPX-0907 was shown to be safe with injection site
      reactions being the most commonly reported adverse event. All breast cancer
      patients (3/3), most of ovarian (5/6) and one third of prostate (3/9) cancer
      patients exhibited detectable immune responses, resulting in a 61% immunological
      response rate. Immune responses were generally observed in patients with better
      disease control after their last prior treatment. Antigen-specific responses were
      detected in 73% of immune responders (44% of evaluable patients) after the first
      vaccination. In 83% of immune responders (50% of evaluable patients), peptide
      specific T cell responses were detected at >=2 time points post vaccination with
      64% of the responders (39% of evaluable patients) showing evidence of immune
      persistence. Immune monitoring also demonstrated the generation of antigen
      specific T cell memory with the ability to secrete multiple Type 1 cytokines.
      CONCLUSIONS: The novel DepoVax formulation promotes multifunctional effector
      memory responses to peptide-based tumor associated antigens. The data supports
      the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting
      further clinical development of the vaccine. This study underscores the
      importance of applying vaccines in clinical settings in which patients are more
      likely to be immune competent. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01095848.

PMID- 22862955
TI  - Depletion of mboa-7, an enzyme that incorporates polyunsaturated fatty acids into
      phosphatidylinositol (PI), impairs PI 3-phosphate signaling in Caenorhabditis
      elegans.
AB  - Phosphatidylinositol (PI) is a constituent of biomembranes and a precursor of all
      phosphoinositides (PIPs). A prominent characteristic of PI is that its sn-2
      position is highly enriched in polyunsaturated fatty acids (PUFAs), such as
      arachidonic acid or eicosapentaenoic acid. However, the biological significance
      of PUFA-containing PI remains unknown. We previously identified Caenorhabditis
      elegans (C. elegans) mboa-7 as an acyltransferase that incorporates PUFAs into
      the sn-2 position of PI. In this study, we performed an RNAi enhancer screen
      against PI kinases and phosphatases using mboa-7 mutants that have a reduced PUFA
      content in PI. Among the genes tested, knockdown of vps-34, a catalytic subunit
      of class III PI 3-kinase that produces PI 3-phosphate (PI3P) from PI, caused
      severe growth defects in mboa-7 mutants. In both vps-34 RNAi-treated wild-type
      worms and mboa-7 mutants, the size of PI3P-positive early endosomes was
      significantly decreased. We also performed an RNAi enhancer screen against PI3P
      related genes and found that, like knockdown of vps-34, knockdown of autophagy
      related genes caused severe growth defects in mboa-7 mutants. Finally, we showed
      that autophagic clearance of protein aggregates is impaired in mboa-7 mutants.
      Taken together, these results suggest that the PUFA chain in PI has a role in
      some PI3P signaling.

PMID- 22862956
TI  - Evidence for a divergence in function between two glucocorticoid receptors from a
      basal teleost.
AB  - BACKGROUND: Duplicated glucocorticoid receptors (GR) are present in most teleost
      fish. The evolutionary advantage of retaining two GRs is unclear, as no subtype
      specific functional traits or physiological roles have been defined. To identify
      factors driving the retention of duplicate GRs in teleosts, the current study
      examined GRs in representatives of two basal ray-finned fish taxa that emerged
      either side of the teleost lineage whole genome duplication event (WGD) event,
      the acipenseriform, Acipenser ruthenus, (pre-WGD) and the osteoglossimorph,
      Pantodon buchholzi, (post-WGD). RESULTS: The study identified a single GR in A.
      ruthenus (ArGR) and two GRs in P. buchholzi (PbGR1 and PbGR2). Phylogenetic
      analyses showed that ArGR formed a distinct branch separate from the teleosts
      GRs. The teleost GR lineage was subdivded into two sublineages, each of which
      contained one of the two P. buchholzi GRs. ArGR, PbGR1 and PbGR2 all possess the
      unique 9 amino acid insert between the zinc-fingers of the DNA-binding domain
      that is present in one of the teleost GR lineages (GR1), but not the other (GR2).
      A splice variant of PbGR2 produces an isoform that lacked these 9 amino acids
      (PbGR2b). Cortisol stimulated transactivation activity of ArGR, PbGR2b and PbGR1
      in vitro; with PbGR2b and PbGR1, the glucocorticoid 11-deoxycortisol was a more
      potent agonist than cortisol. The hormone sensitivity of PbGR2b and PbGR1
      differed in the transactivation assay, with PbGR2b having lower EC50 values and
      greater fold induction. CONCLUSIONS: The difference in transactivation activity
      sensitivity between duplicated GRs of P. buchholzi suggests potential functional
      differences between the paralogs emerged early in the teleost lineage. Given the
      pleiotropic nature of GR function in vertebrates, this finding is in accordance
      with the hypothesis that duplicated GRs were potentially retained through
      subfunctionalisation followed by gene sharing. A 9 amino acid insert in the DNA
      binding domain emerged in basal ray-finned fish GRs. However, the presence of a
      PbGR2 splice variant that lacks this insert, as well as the loss of the exon
      encoding these amino acids in the genes encoding for other teleost GR2 suggests
      the selection of two receptors with different DNA-binding domain structures in
      teleosts.

PMID- 22862957
TI  - Resuscitation by hyperbaric exposure from a venous gas emboli following
      laparoscopic surgery.
AB  - Venous gas embolism is common after laparoscopic surgery but is only rarely of
      clinical relevance. We present a 52 year old woman undergoing laparoscopic
      treatment for liver cysts, who also underwent cholecystectomy. She was
      successfully extubated. However, after a few minutes she developed cardiac arrest
      due to a venous carbon dioxide (CO2) embolism as identified by transthoracic
      echocardiography and aspiration of approximately 7 ml of gas from a central
      venous catheter. She was resuscitated and subsequently treated with hyperbaric
      oxygen to reduce the size of remaining gas bubbles. Subsequently the patient
      developed one more episode of cardiac arrest but still made a full recovery. The
      courses of events indicate that bubbles had persisted in the circulation for a
      prolonged period. We speculate whether insufficient CO2 flushing of the
      laparoscopic tubing, causing air to enter the peritoneal cavity, could have
      contributed to the formation of the intravascular gas emboli. We conclude that
      persistent resuscitation followed by hyperbaric oxygen treatment after venous gas
      emboli contributed to the elimination of intravascular bubbles and the favourable
      outcome for the patient.

PMID- 22862958
TI  - Androgens coordinate neurotransmitter-related gene expression in male whiptail
      lizards.
AB  - Sex steroid hormones coordinate neurotransmitter systems in the male brain to
      facilitate sexual behavior. Although neurotransmitter release in the male brain
      has been well documented, little is known about how androgens orchestrate changes
      in gene expression of neurotransmitter receptors. We used male whiptail lizards
      (Cnemidophorus inornatus) to investigate how androgens alter neurotransmitter
      related gene expression in brain regions involved in social decision making. We
      focused on three neurotransmitter systems involved in male-typical sexual
      behavior, including the N-methyl-d-aspartate (NMDA) glutamate receptor, nitric
      oxide and dopamine receptors. Here, we show that in androgen-treated males, there
      are coordinated changes in neurotransmitter-related gene expression. In androgen
      implanted castrates compared with blank-implanted castrates (control group), we
      found associated increases in neuronal nitric oxide synthase gene expression in
      the nucleus accumbens (NAcc), preoptic area and ventromedial hypothalamus, a
      decrease of NR1 gene expression (obligate subunit of NMDA receptors) in the
      medial amygdaloid area and NAcc and a decrease in D1 and D2 dopamine receptor
      gene expression in the NAcc. Our results support and expand the current model of
      androgen-mediated gene expression changes of neurotransmitter-related systems
      that facilitate sexual behavior in males. This also suggests that the proposed
      evolutionarily ancient reward system that reinforces sexual behavior in amniote
      vertebrates extends to reptiles.

PMID- 22862959
TI  - Age-associated alterations in CD8alpha+ dendritic cells impair CD8 T-cell
      expansion in response to an intracellular bacterium.
AB  - Age-associated decline in immunity to infection has been documented across
      multiple pathogens, yet the relative contributions of the aged priming
      environment and of lymphocyte-intrinsic defects remain unclear. To address the
      impact of the aging environment on T-cell priming, adult naive OT-I TCR
      transgenic CD8 T cells, specific for the H-2Kb-restricted immunodominant OVA(257
      264) epitope, were transferred into adult or old recipient mice infected with the
      recombinant intracellular bacterium Listeria monocytogenes carrying the chicken
      ovalbumin protein (Lm-OVA). We consistently found that adult OT-I CD8 expansion
      was reduced in aged recipient mice, and this correlated with numeric, phenotypic,
      and functional defects selectively affecting CD8alpha+ dendritic cells (DC).
      Following Lm-OVA infection, aged mice failed to accumulate CD8alpha+ DC in the
      spleen, and these cells expressed much lower levels of critical costimulatory
      molecules in the first three days following infection. Further, aged CD8alpha+ DC
      showed impaired uptake of the bacteria at very early time points following
      infection. Treatment of aged mice with Flt3 ligand (Flt3L) improved the number of
      DC present in the spleen prior to Lm-OVA infection, and improved, but did not
      reconstitute, OT-I expansion to Lm-OVA infection. These results suggest that age
      associated changes in antigen uptake, pathogen sensing, and/or antigen
      presentation contribute to impaired adaptive immune responses to microbial
      pathogens with aging.

PMID- 22862960
TI  - Factors associated with consultation behaviour for primary symptoms potentially
      indicating colorectal cancer: a cross-sectional study on response to symptoms.
AB  - BACKGROUND: Little data exists on the factors associated with health care seeking
      behaviour for primary symptoms of colorectal cancer (CRC). This study aimed to
      identify individual, provider and psychosocial factors associated with (i) ever
      seeking medical advice and (ii) seeking early medical advice for primary symptoms
      of colorectal cancer (CRC). METHODS: 1592 persons aged 56-88 years randomly
      selected from the Hunter Community Study (HCS) were sent a questionnaire.
      RESULTS: Males and those who had received screening advice from a doctor were at
      significantly higher odds of ever seeking medical advice for rectal bleeding.
      Persons who had private health coverage, consulted a doctor because the 'symptom
      was serious', or who did not wait to consult a doctor for another reason were at
      significantly higher odds of seeking early medical advice (< 2 weeks). For change
      in bowel habit, persons with lower income, within the healthy weight range, or
      who had discussed their family history of CRC irrespective of whether informed of
      'increased risk' were at significantly higher odds of ever seeking medical
      advice. Persons frequenting their GP less often and seeing their doctor because
      the symptom persisted were at significantly higher odds of seeking early medical
      advice (< 2 weeks). CONCLUSIONS: The seriousness of symptoms, importance of early
      detection, and prompt consultation must be articulated in health messages to at
      risk persons. This study identified modifiable factors, both individual and
      provider-related to consultation behaviour. Effective health promotion efforts
      must heed these factors and target sub-groups less likely to seek early medical
      advice.

PMID- 22862961
TI  - The novel GLP-1-gastrin dual agonist, ZP3022, increases beta-cell mass and
      prevents diabetes in db/db mice.
AB  - AIM: Diabetes is characterized by beta-cell deficiency, and therefore restoration
      of beta-cell function has been suggested as a potential therapy. We hypothesized
      that a novel glucagon-like peptide-1 (GLP-1)-gastrin dual agonist, ZP3022,
      improves glycaemic control via improvement of beta-cell status in db/db mice.
      METHODS: Diabetic mice were studied following short- or long-term treatment with
      either the GLP-1-gastrin dual agonist or the commercially available GLP-1
      agonists (exendin-4 and liraglutide). The effects on glycaemic control were
      addressed by repeated glucose tolerance tests and/or measurements of HbA1c
      levels, and pancreatic islet and beta-cell masses were determined by stereology.
      RESULTS: ZP3022 and the pure GLP-1 agonists improved glycaemic control after both
      short- and long-term treatment compared with vehicle. Interestingly, the effect
      was sustainable only in mice treated with ZP3022. Stereology data displayed a
      dose-dependent increase of beta-cell mass (p < 0.05) following treatment with
      ZP3022, whereas no significant effect of liraglutide was observed (beta-cell
      mass: vehicle 3.7 +/- 0.2 mg; liraglutide (30 nmol/kg) 3.4 +/- 0.5 mg; ZP3022 (30
      nmol/kg) 4.3 +/- 0.4 mg and ZP3022 (100 nmol/kg) 5.2 +/- 0.4 mg). CONCLUSION: The
      novel GLP-1-gastrin dual agonist, ZP3022, improved glycaemic control in db/db
      mice, and pancreatic islet and beta-cell mass increased significantly following
      treatment with ZP3022 compared with vehicle.

PMID- 22862962
TI  - Molecular pathways for glucose homeostasis, insulin signaling and autophagy in
      hepatitis C virus induced insulin resistance in a cellular model.
AB  - Chronic HCV infection induces insulin resistance (IR). We studied this in a
      persistently infected cell line with defects in glucose homeostasis resulting
      from the phosphorylation of glycogen synthase (GS Ser641) and GS kinase isoform
      3beta (GSK 3betaSer9). Reversal of these effects in cells cured of HCV with
      interferon supports viral specificity. Insulin signaling was disrupted by IRS-1
      Ser312 phosphorylation and dysregulation of the Akt pathway. In infected cells,
      active autophagy was revealed by the formation of LC3 puncta or by increased
      levels (50-200%) of the markers Beclin 1 and conjugated Atg5/Atg12. Inhibition of
      autophagy by 3-methyl-adenine (3-MA) reduced Beclin1 levels, inhibited IRS-1
      Ser312 or GS Ser641 phosphorylation and decreased viral load. Furthermore, IRS-1
      Ser312 and Beclin1 were co-immunoprecipitated suggesting that they interact. It
      thus appears that HCV infection disturbs glucose homeostasis or insulin signaling
      to induce IR and also elicits autophagy that may contribute to this process.

PMID- 22862963
TI  - Endogenous sex hormones, blood pressure change, and risk of hypertension in
      postmenopausal women: the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: Sex steroid hormones have been postulated to involve in blood pressure
      (BP) regulation. We examine the association of endogenous sex hormone levels with
      longitudinal change of BP and risk of developing hypertension in initially
      normotensive postmenopausal women. METHODS: We conducted prospective analysis
      among 619 postmenopausal women free of hypertension at baseline in the Multi
      Ethnic Study of Atherosclerosis (MESA). Change of BP and development of incident
      hypertension were assessed during a mean of 4.8 years follow-up. RESULTS: After
      adjusting for age, race/ethnicity, and lifestyle factors, baseline serum
      estradiol (E(2)), total and bioavailable testosterone (T), dehydroepiandrosterone
      (DHEA) were each positively associated and sex-hormone binding globulin (SHBG)
      was inversely associated with risk of hypertension. Additional adjustment for
      body mass index eliminated the associations for E(2) and T but only attenuated
      the associations for DHEA and SHBG. The corresponding multivariable hazard ratios
      (95% CIs) in the highest quartile were 1.28 (0.83-1.97) for E(2), 1.38 (0.89
      2.14) for total T, 1.42 (0.90-2.23) for bioavailable T, 1.54 (1.02-2.31) for
      DHEA, and 0.48 (0.30-0.76) for SHBG. Adjustment for fasting glucose, insulin, and
      C-reactive protein further attenuated the association for DHEA but not for SHBG.
      Associations of sex hormones with longitudinal BP change were similar.
      CONCLUSION: In postmenopausal women, higher endogenous E(2), T, and DHEA and
      lower SHBG were associated with higher incidence of hypertension and greater
      longitudinal rise in BP. The associations for E(2), T, and DHEA were mostly
      explained by adiposity, while the association for SHBG was independent of
      measures of adiposity, insulin resistance, and systemic inflammation.

PMID- 22862964
TI  - Patients with chronic gastrointestinal ischemia have a higher cardiovascular
      disease risk and mortality.
AB  - OBJECTIVES: We determined the prevalence of classical risk factors for
      atherosclerosis and mortality risk in patients with CGI. METHODS: A case-control
      study was conducted. Patients referred with suspected CGI underwent a standard
      work-up including risk factors for atherosclerosis, radiological imaging of
      abdominal vessels and tonometry. Cases were patients with confirmed
      atherosclerotic CGI. Controls were healthy subjects previously not known with
      CGI. The mortality risk was calculated as standardized mortality ratio derived
      from observed mortality, and was estimated with ten-year risk of death using
      SCORE and PREDICT. RESULTS: Between 2006 and 2009, 195 patients were evaluated
      for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was
      diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender,
      diabetes, hypercholesterolemia, a personal and family history of cardiovascular
      disease (CVD), and current smoking are highly associated with CGI. After
      adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI
      1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR
      21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a
      higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to
      controls. During follow-up of 116 person-years, standardized mortality rate was
      higher in CGI patients (3.55; 95% CI 1.70-6.52). CONCLUSIONS: Patients with
      atherosclerotic CGI have an increased estimated CVD risk, and severe excess
      mortality. Secondary cardiovascular prevention therapy should be advocated in
      patients with CGI.

PMID- 22862965
TI  - Paucity of CD34-positive cells and increased expression of high-mobility group
      box 1 in coronary thrombus with type 2 diabetes mellitus.
AB  - To examine the presence of CD34-positive cells and intranuclear factors in acute
      coronary thrombi, we compared thrombi in patients with type 2 diabetes mellitus
      (DM, n = 21) and without DM (n = 29). Immunohistochemical staining revealed the
      constitutive presence of platelets, fibrin, erythrocytes, neutrophils,
      extracellular high-mobility group box 1 (HMGB-1), and histone H3 in all thrombi.
      There were significantly more oval or flat CD34-positive cells and significantly
      larger HMGB-1-positive areas in the thrombi from patients with DM. The flat CD34
      positive cells expressed ecto-nucleoside triphosphate diphosphohydrolase (a
      platelet aggregation inhibitor). The number of CD34-positive cells was negatively
      correlated with the serum levels of glucose and hemoglobin A1c, whereas the HMGB
      1-positive area was positively correlated with the levels of serum glucose. The
      paucity of CD34-positive cells and the high levels of HMGB-1 expression in acute
      coronary thrombi from patients with type 2 DM could facilitate thrombus
      formation.

PMID- 22862966
TI  - HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by
      disrupting lipid rafts in antigen presenting cells.
AB  - OBJECTIVE: Depletion of cholesterol by methyl-beta-cyclodextrin (MCD) on peptide
      loaded antigen presenting cells (APCs) inhibits antigen presentation and T cell
      activation. However, whether membrane cholesterol efflux induced by high-density
      lipoprotein (HDL) and apolipoprotein A-I (apoA-I) also results in inhibition of
      antigen presentation and T cell activation is still unknown. METHODS AND RESULTS:
      Various types of APCs, including B cells, macrophages and dendritic cells (DCs),
      were first loaded with antigen, then incubated with HDL and apoA-I to decrease
      cellular membrane cholesterol content. After being treated with HDL and apoA-I,
      APCs demonstrated decreased potential to activate T cells, and this decrease
      correlated with an increase in cholesterol efflux from APCs. Cholesterol
      repletion reversed the inhibitory effects of HDL and apoA-I, demonstrating that
      the observed reduction in T cell proliferation is mediated through cholesterol.
      Furthermore, lipid raft analysis showed that HDL and apoA-I reduced cholesterol
      and major histocompatibility (MHC) class II protein content in lipid rafts,
      suggesting that cholesterol efflux from APCs to HDL and apoA-I inhibits antigen
      presentation and T cell activation by reducing lipid rafts assembly in APCs.
      CONCLUSION: HDL and apoA-I inhibit the capacity of APCs to stimulate T cell
      activation, and this inhibition can be attributed to cholesterol efflux and the
      ensuing disruption of plasma membrane lipid rafts in APCs. Overall, these
      findings suggest that cholesterol efflux mediated by HDL and apoA-I may serve to
      link immunity and cardioprotection.

PMID- 22862967
TI  - The role of versican G3 domain in regulating breast cancer cell motility
      including effects on osteoblast cell growth and differentiation in vitro -
      evaluation towards understanding breast cancer cell bone metastasis.
AB  - BACKGROUND: Versican is detected in the interstitial tissues at the invasive
      margins of breast carcinoma, is predictive of relapse, and negatively impacts
      overall survival rates. The versican G3 domain is important in breast cancer cell
      growth, migration and bone metastasis. However, mechanistic studies evaluating
      versican G3 enhanced breast cancer bone metastasis are limited. METHODS: A
      versican G3 construct was exogenously expressed in the 66c14 and the MC3T3-E1
      cell line. Cells were observed through light microscopy and viability analyzed by
      Coulter Counter or determined with colorimetric proliferation assays. The Annexin
      V-FITC apoptosis detection kit was used to detect apoptotic activity. Modified
      Chemotactic Boyden chamber migration invasion assays were applied to observe
      tumor migration and invasion to bone stromal cells and MC3T3-E1 cells. Alkaline
      phosphatase (ALP) staining and ALP ELISA assays were performed to observe ALP
      activity in MC3T3-E1 cells. RESULTS: In the four mouse breast cancer cell lines
      67NR, 66c14, 4T07, and 4T1, 4T1 cells expressed higher levels of versican, and
      showed higher migration and invasion ability to MC3T3-E1 cells and primary bone
      stromal cells. 4T1 conditioned medium (CM) inhibited MC3T3-E1 cell growth, and
      even lead to apoptosis. Only 4T1 CM prevented MC3T3-E1 cell differentiation,
      noted by inhibition of alkaline phosphatase (ALP) activity. We exogenously
      expressed a versican G3 construct in a cell line that expresses low versican
      levels (66c14), and observed that the G3-expressing 66c14 cells showed enhanced
      cell migration and invasion to bone stromal and MC3T3-E1 cells. This observation
      was prevented by selective EGFR inhibitor AG1478, selective MEK inhibitor PD
      98059, and selective AKT inhibitor Triciribine, but not by selective JNK
      inhibitor SP 600125. Versican G3 enhanced breast cancer cell invasion to bone
      stromal cells or osteoblast cells appears to occur through enhancing EGFR/ERK or
      AKT signaling. G3 expressing MC3T3-E1 cells showed inhibited cell growth and cell
      differentiation when cultured with TGF-beta1 (1 ng/ml), and expressed enhanced
      cell apoptosis when cultured with TNF-alpha (2 ng/ml). Enhanced EGFR/JNK
      signaling appears to be responsible for G3 enhanced osteoblast apoptosis and
      inhibited osteoblast differentiation. Whereas repressed expression of GSK-3beta
      (S9P) contributes to G3 inhibited osteoblast growth. Versican G3 functionality
      was dependent on its EGF-like motifs. Without the structure of EGF-like repeats,
      the G3 domain would not confer enhancement of tumor cell migration and invasion
      to bone with concordant inhibition of osteoblast differentiation and promotion of
      osteoblast apoptosis. CONCLUSIONS: Versican enhances breast cancer bone
      metastasis not only through enhancing tumor cell mobility, invasion, and survival
      in bone tissues, but also by inhibiting pre-osteoblast cell growth,
      differentiation, which supply favorable microenvironments for tumor metastasis.

PMID- 22862968
TI  - 'It's a can of worms': understanding primary care practitioners' behaviours in
      relation to HPV using the Theoretical Domains Framework.
AB  - BACKGROUND: The relationship between infection with high-risk human
      papillomavirus (HPV) and cervical cancer is transforming cervical cancer
      prevention. HPV tests and vaccinations have recently become available. In
      Ireland, as elsewhere, primary care practitioners play a key role in prevention.
      ATHENS (A Trial of HPV Education and Support) aims to develop a theory-based
      intervention to support primary care practitioners in their HPV-related practice.
      This study, the first step in the intervention development process, aimed to:
      identify HPV-related clinical behaviours that the intervention will target;
      clarify general practitioners' (GPs') and practice nurses' roles and
      responsibilities; and determine factors that potentially influence clinical
      behaviour. A secondary objective was to informally assess the utility of the
      Theoretical Domains Framework (TDF) in understanding clinical behaviours in an
      area with an evolving evidence-base. METHODS: In-depth semi-structured telephone
      interviews were conducted with GPs and practice nurses. The topic guide, which
      contained open questions and HPV-related clinical scenarios, was developed
      through literature review and clinical experience. Interview transcripts were
      content-analysed using the TDF as the coding framework. RESULTS: 19 GPs and 14
      practice nurses were interviewed. The major HPV-related clinical behaviours were:
      initiating a discussion about HPV infection with female patients;
      offering/recommending HPV vaccination to appropriate patients; and answering
      patients' questions about HPV testing. While the responsibility for taking smears
      was considered a female role, both male and female practitioners dealt with HPV
      related issues. All 12 theoretical domains arose in relation to HPV infection;
      the domains judged to be most important were: knowledge, emotion, social
      influences, beliefs about capabilities and beliefs about consequences. Eleven
      domains emerged in relation to HPV vaccination, with beliefs about consequences,
      social influences, knowledge and environmental context and resources judged to be
      the most important. Nine domains were relevant to HPV testing, with knowledge and
      beliefs about capabilities judged to be the most important. CONCLUSIONS: The
      findings confirm the need for an intervention to support primary care
      practitioners around HPV and suggest it should target a range of theoretical
      domains. The TDF proved valuable in analysing qualitative data collected using a
      topic guide not specifically designed to capture TDF domains and understanding
      clinical behaviours in an area with an evolving evidence-base.

PMID- 22862969
TI  - Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma.
AB  - Recent studies have shown that some members of the tripartite motif-containing
      protein (TRIM) family, which is characterized by a conserved RING finger, B-box,
      and coiled-coil domains, function as important regulators for carcinogenesis. In
      this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene
      through overexpression in gastric cancer. We analyzed seven gastric cancer cell
      lines and 112 primary tumors, which were curatively resected in our hospital
      between 2001 and 2003. Expression of the TRIM44 protein was detected in gastric
      cancer cell lines (2/7 cell lines; 29%) and primary tumor samples of gastric
      cancer (29/112 cases; 25%). Knockdown of TRIM44 expression using several specific
      siRNAs inhibited the proliferation, migration, and invasion of TRIM44
      overexpressing cells. Overexpression of the TRIM44 protein was significantly
      correlated with an advanced type of macroscopic appearance, lymphatic invasion,
      and higher recurrence rate. TRIM44-overexpressing tumors had a worse overall rate
      of survival than those with non-expressing tumors (P = 0.0038, log-rank test) in
      both intensity and proportion expression-dependent manner. TRIM44 positivity was
      independently associated with worse outcome in multivariate analysis (P = 0.0233,
      hazard ratio 3.37 [1.18-9.64]). These findings suggest that TRIM44 plays a
      crucial role in tumor cell proliferation through its overexpression, and
      highlight its usefulness as a predictor and potential therapeutic target in
      gastric cancer.

PMID- 22862970
TI  - Radiation risk in low-dose maxillofacial radiography.

PMID- 22862971
TI  - Influence of dentures in the initial occurrence site on the prognosis of
      bisphosphonate-related osteonecrosis of the jaws: a retrospective study.
AB  - OBJECTIVE: This retrospective cohort study was conducted to investigate the
      influence of wearing dentures in the initial occurrence site of bisphosphonate
      related osteonecrosis of the jaws (BRONJ). STUDY DESIGN: A questionnaire
      regarding the prevalence, therapy, and outcome of jawbone lesions during 2006-08
      was mailed to 248 medical institutions with an oral and maxillofacial surgery
      department in Japan. RESULTS: Ninety-nine patients wearing dentures had
      significantly shorter duration until occurrence than 151 patients not wearing
      dentures. In addition, remission of BRONJ affecting the mandibular canine and
      premolar region in denture-wearing patients was significantly more difficult.
      Poor oral hygiene status was found to affect significantly the prognosis of BRONJ
      in denture-wearing patients. Alcohol habit also delayed remission, but high body
      mass index promoted remission. CONCLUSION: Wearing a denture in the initial
      occurrence site of BRONJ was shown to influence the prognosis of BRONJ,
      especially in mandibular denture-wearing patients.

PMID- 22862972
TI  - Evaluation of select neurophysiological, clinical and psychological tests for
      burning mouth syndrome.
AB  - OBJECTIVE: The objective of this study was to identify, among an array of
      potential risk factors for burning mouth syndrome (BMS), those that are
      potentially the most significant in the development of the disease. STUDY DESIGN:
      Sixty-three participants, divided into group I (with BMS: 33 patients ages 41 to
      82 years [mean age: 61.5 +/- 9.4]) and group II (without BMS: 30 healthy
      volunteers ages 42-83 years [mean age: 60.5 +/- 10.5]) were studied. All
      underwent a dental examination and psychological tests. Neurological tests
      (neurophysiological test, electroneurography, and tests of the autonomic nervous
      system) were performed. Mean parameters were analyzed by Student t test, Kruskal
      Wallis test, and chi(2) test, and multifactor analysis was performed with
      logistic regression and by calculating the odds ratio. RESULTS: In the logistic
      regression test, 3 factors were significant in the etiopathogenesis of BMS: a
      value more than 39 MUV for the amplitude of the positive peak of the potential
      induced by stimulating the trigeminal nerve on the left side (P2-L); a value
      above 5.96 ms for the latency of wave V of the brainstem auditory evoked
      potentials on the right side (V-R); and a value over 2.35 ms for the latency of
      the sensory ulnar nerve response. CONCLUSIONS: The BMS sufferer was characterized
      as having mild sensory and autonomic small fiber neuropathy with concomitant
      central disorders.

PMID- 22862973
TI  - Hospitalizations primarily attributed to dental conditions in the United States
      in 2008.
AB  - OBJECTIVE: The objective of this study was to provide estimates of
      hospitalizations attributed to oral health related conditions in the United
      States (US). STUDY DESIGN: The nationwide inpatient sample (NIS) of the
      Healthcare Cost and Utilization Project (HCUP) for 2008 was used. Hospital
      admissions with a primary diagnosis of dental/oral health-related conditions were
      identified using ICD-9-CM diagnosis codes. RESULTS: A total of 50,658 hospital
      admissions were primarily attributed to oral health-related conditions in 2008.
      Total US hospitalization charges were $1.218 billion. Total US hospitalization
      days were 174,496 days. CONCLUSIONS: The current study examines outcomes in
      patients hospitalized primarily for dental/oral health-related conditions. Of
      39,885,120 hospitalizations that occurred in the US, a total of 50,658 (1.27%)
      were primarily attributed to dental-related conditions. Substantial resources are
      spent in treating dental-related conditions in hospital settings.

PMID- 22862974
TI  - Oral health of the elderly with Alzheimer's disease.
AB  - OBJECTIVE: The objective of this study was to describe the oral health of elderly
      people diagnosed with Alzheimer's disease (AD). STUDY DESIGN: Thirty elderly
      subjects with AD (mild, moderate, and severe) and 30 without AD (controls) were
      included in the study. Volunteer-reported oral health data were collected using
      the General Oral Health Assessment Index (GOHAI). Demographic and oral
      characteristics were assessed, including the number of natural teeth; number of
      decayed, missing, and filled teeth (DMTF); oral health index (OHI); removable
      prosthesis conditions; and oral pathologies. RESULTS: GOHAI values were similar
      for both groups. Compared with the controls, the subjects with AD had a higher
      age, DMTF, OHI, and number of oral pathologies and a lower educational level and
      number of natural teeth. CONCLUSIONS: Elderly subjects with AD had poorer oral
      health than those without the disease. Despite the positive self-perception of
      their oral health, the oral health of subjects with AD tended to decline as their
      disease progressed.

PMID- 22862975
TI  - F2-Isoprostanes in soft oral tissues and degree of oral disability after
      mandibular third molar surgery.
AB  - OBJECTIVE: The aim of this study was to test the value of F(2)-isoprostane (F(2)
      IsoP) levels in the pericoronal gingiva as a potential predictor of oral
      disability after mandibular third molar (M3M) surgery. STUDY DESIGN: Thirteen
      patients (5 male, 8 female) with partially impacted M3M were enrolled.
      Pericoronal soft tissues histology was obtained, gingival F(2)-IsoPs were
      measured by gas chromatography/negative-ion chemical ionization tandem mass
      spectrometry, and health-related quality of life (HRQOL) scores were assessed.
      RESULTS: A variable degree of pericoronitis was evident before the M3M surgery,
      with a mean level of pericoronal F(2)-IsoPs of 634.8 +/- 193.5 pg/mg of tissue. A
      significant positive correlation between pericoronal F(2)-IsoPs and HRQOL was
      observed in male (r(s) = 0.440; P = .0011), but not female (r(s) = -0.062; P =
      .5124) patients. CONCLUSIONS: Levels of F(2)-IsoPs in the pericoronal soft
      tissues are correlated with the degree of oral disability after M3Ms surgery in
      male, but not female, patients.

PMID- 22862976
TI  - Frequency and genotype distribution of multiple human papillomavirus infections
      in cancer of the head and neck in a Mexican population.
AB  - OBJECTIVE: The aim of this study was to determine the frequency and genotype
      distribution of single and multiple human papillomavirus (HPV) infections in head
      and neck squamous cell carcinomas (HNSCCs) in a Mexican population and to assess
      their associations with smoking and drinking habits and clinicopathologic
      characteristics. STUDY DESIGN: A cross-sectional study was performed on a sample
      of patients diagnosed with HNSCCs. Tumor DNA was amplified using polymerase chain
      reaction with HPV consensus and multiplex primers. The associations among HPV
      status, survival, and clinical characteristics were analyzed. RESULTS: Sixteen of
      the 43 HNSCCs were HPV positive. HPV16 was the most prevalent type, with single
      infections present in 5 cases, whereas another 5 cases were combined with HPV56
      infection. There was a significant association between HPV infection and
      oropharyngeal cancers. HPV positivity was associated with overall survival at a
      nearly significant P level of 0.06. CONCLUSIONS: Our data support the importance
      of HPV infection in oropharyngeal cancer, with a trend toward higher survival in
      HPV-positive cases.

PMID- 22862977
TI  - The use of quantitative cytology in identifying high-risk oral lesions in
      community practice.
AB  - OBJECTIVE: This study evaluated whether quantitative cytology (QC) can disclose
      abnormal DNA content (aneuploidy) and abnormal nuclear morphology of high-risk
      potentially malignant disorders (PMDs) of the oral mucosa found in the community
      in reference to clinicohistopathologic features. STUDY DESIGN: A total of 171
      patients at community-based clinic with suspicious oral lesions were evaluated
      with concurrent but independent histopathologic and QC assessments. RESULTS: QC
      positive results were associated with oral lesions with higher clinical risk
      factors: large size, nonhomogeneous surface texture, and located at high-risk
      anatomic sites. Only 3% of benign/reactive and 5% of low-risk PMDs were QC
      positive, while 92% of high-risk PMDs and 88% of squamous cell carcinomas (SCCs)
      were QC positive. The sensitivity and specificity of QC for detection of high
      grade dysplasia/SCC were 89% and 97%. CONCLUSIONS: QC could serve as an
      adjunctive tool for the detection of high-risk PMD/SCC requiring immediate
      clinical care.

PMID- 22862978
TI  - Multiple cemental tears.
AB  - A cemental tear is a pathologic condition in which a complete or incomplete
      separation of the cementum occurs along the root surface and is usually
      accompanied by a deep periodontal pocket. Past articles report that the incidence
      of cemental tears has usually been limited to 1 tooth per individual. We
      encountered a clinical case with cemental tears involving 14 teeth in 1
      individual. Multiple cemental tears in 1 individual have not been previously
      described in the dental literature. We present the clinical and pathologic
      features of this rare case and suggest that the probable cause of multiple
      cemental tears is structural weakness of the cementum.

PMID- 22862979
TI  - Comparison of cone-beam computed tomography incidental findings between patients
      with moderate/severe obstructive sleep apnea and mild obstructive sleep
      apnea/healthy patients.
AB  - OBJECTIVE: The objective of this study was to compare the incidental radiographic
      findings in the maxillofacial structures and the pharyngeal airway between
      subjects with moderate/severe obstructive sleep apnea (OSA) and mild OSA/healthy
      subjects using cone-beam computed tomography (CBCT) scans. STUDY DESIGN: A total
      of 53 subjects with moderate/severe OSA (with a Respiratory Disturbance Index
      [RDI] >= 15 events/h) and 33 mild OSA/healthy subjects (RDI < 15), based on
      ambulatory somnographic assessment, were recruited. Supine CBCTs were taken and
      sent for radiological report. The incidental findings were compared between the 2
      groups. RESULTS: Moderate/severe subjects had larger prevalence of conchae
      bullosa, hypertrophic turbinates, hypertrophic tonsils, elongated or posteriorly
      placed soft palate, narrower airway, enlarged tongue, and focal calcifications,
      although no significant differences were found. CONCLUSIONS: CBCT is useful in
      identifying maxillofacial and airway anomalies that could interfere with normal
      breathing; however, no significant difference was found in prevalence of
      incidental findings between subjects with moderate/severe OSA and mild
      OSA/healthy subjects. Further studies are necessary to generalize our results.

PMID- 22862980
TI  - Ultrasonographic appearances of mucoepidermoid carcinoma of the salivary glands.
AB  - OBJECTIVE: The objective of this study was to investigate the ability of
      sonography for diagnosis of mucoepidermoid carcinoma (MEC) in the salivary
      glands. STUDY DESIGN: Sonographic images of 74 cases were analyzed
      retrospectively; the features evaluated included size, echogenicity, shape,
      internal structure, distal acoustic enhancement, and regional lymph node
      enlargement and vascularization, and categorized them into 3 groups based on
      histology (low, intermediate, and high grade). RESULTS: The lesion size of low
      grade MEC was smaller than those of intermediate- and high-grade MEC. MEC lesions
      of the salivary glands were mostly associated with heterogeneous echotexture,
      indistinct margins, irregular shape, and absence of distal acoustic enhancement.
      They sometimes showed cystic areas, calcifications, regional lymph node
      enlargement, or were well vascularized on Doppler. There were no significant
      sonographic differences in low-, intermediate-, and high-grade MEC. CONCLUSIONS:
      Salivary MEC presents a variety of sonographic appearances, which would aid in
      the diagnosis of salivary MEC.

PMID- 22862981
TI  - Fibro-osseous disease: harmonizing terminology with biology.
AB  - Classification systems and associated terminology are inherently slow in
      reflecting rapidly unfolding scientific discoveries in the mechanism and
      presentation of diseases. Misleading concepts, which often have historical value
      only, may become entrenched in the literature, leading to confusion and
      inaccurate communication. The purpose of this communication is to stimulate
      discussion and debate on inappropriate terminology associated with fibro-osseous
      disease that continues to be perpetuated in the literature. Use of the terms
      "cementum," "aggressive," "active," "gigantiform," and "maturation" are
      questioned, and the criteria applied to the interpretation of secondary changes
      in fibro-osseous lesions critically are evaluated.

PMID- 22862982
TI  - Assessment of radiation exposure in dental cone-beam computerized tomography with
      the use of metal-oxide semiconductor field-effect transistor (MOSFET) dosimeters
      and Monte Carlo simulations.
AB  - OBJECTIVES: The aims of this study were to assess the organ and effective dose
      (International Commission on Radiological Protection (ICRP) 103) resulting from
      dental cone-beam computerized tomography (CBCT) imaging using a novel metal-oxide
      semiconductor field-effect transistor (MOSFET) dosimeter device, and to assess
      the reliability of the MOSFET measurements by comparing the results with Monte
      Carlo PCXMC simulations. STUDY DESIGN: Organ dose measurements were performed
      using 20 MOSFET dosimeters that were embedded in the 8 most radiosensitive organs
      in the maxillofacial and neck area. The dose-area product (DAP) values attained
      from CBCT scans were used for PCXMC simulations. The acquired MOSFET doses were
      then compared with the Monte Carlo simulations. RESULTS: The effective dose
      measurements using MOSFET dosimeters yielded, using 0.5-cm steps, a value of 153
      MUSv and the PCXMC simulations resulted in a value of 136 MUSv. CONCLUSIONS: The
      MOSFET dosimeters placed in a head phantom gave results similar to Monte Carlo
      simulations. Minor vertical changes in the positioning of the phantom had a
      substantial affect on the overall effective dose. Therefore, the MOSFET
      dosimeters constitute a feasible method for dose assessment of CBCT units in the
      maxillofacial region.

PMID- 22862983
TI  - Redefining osteoradionecrosis.

PMID- 22862985
TI  - Craniofacial bone tissue engineering.
AB  - There are numerous conditions, such as trauma, cancer, congenital malformations,
      and progressive deforming skeletal diseases, that can compromise the function and
      architectonics of bones of craniofacial region. The need to develop new
      approaches for treatment of these disorders arises from the fact that
      conventional therapeutic strategies face many obstacles and limitations. The use
      of tissue engineering in regeneration of craniofacial bone structures is a very
      promising possibility and a great challenge for researchers and practitioners.
      Developments in stem cell biology and engineering have led to the discovery of
      different stem cell populations and biodegradable materials with suitable
      properties. This review summarizes the current achievements in tissue engineering
      of craniofacial bone, temporomandibular joint, and periodontal ligament.

PMID- 22862986
TI  - Oral myiasis: does an indication for surgical treatment still exist? Two case
      reports.
AB  - OBJECTIVE: Oral myiasis is a rare infection for which treatment protocol has not
      yet been established. This article presents 2 cases treated with a combination of
      topical application of sulfuric ether and surgery. The reasons for the use of
      surgical therapy, as well as the possible advantages and disadvantages of drug
      based treatments, are discussed. CASE REPORT: Two cases of oral myiasis are
      described, the first being observed in a 9-year-old child with hypotonic cerebral
      palsy, and the second in a 52-year-old adult, alcohol-dependent, both showing
      infection in the gingival sulcus. Both cases were successfully treated in a
      process that involved topical application of sulfuric ether, mechanical removal
      of larvae, and surgical debridement. CONCLUSIONS: Oral myiasis can be treated
      effectively with surgery after topical application of sulfuric ether. The use of
      drugs may suggest a therapeutic alternative, but still requires further study and
      experience to be implemented, especially in individuals with neurological
      disorders.

PMID- 22862987
TI  - Descending necrotizing mediastinitis associated with an infected dentigerous
      cyst.
AB  - Descending necrotizing mediastinitis (DNM) is a rare condition in which an
      infection from the head and neck propagates into the mediastinum. The most common
      cause of DNM is odontogenic infection. DNM is spread by the fascial planes from
      the neck into the mediastinum and requires an aggressive surgical drainage
      through cervical and thoracic approaches. We report on a 67-year-old male
      patient, who had acute mediastinitis related to an infected dentigerous cyst in
      the left parasymphyseal region. A multidisciplinary team approach was used to
      treat the patient. The team consisted of thoracic surgeons, maxillofacial
      surgeons, and a radiologist. After the drainage of the mediastinum and pleural
      cavity, the cyst was enucleated. The patient was discharged at the 42nd day of
      hospitalization. The aim of this article is to present diagnosis, management, and
      follow-up of an infected dentigerous cyst that caused DNM.

PMID- 22862988
TI  - Ghost cell odontogenic carcinoma arising in the background of a benign calcifying
      cystic odontogenic tumor of the mandible.
AB  - Ghost cell odontogenic carcinoma (GCOC) is a rare malignant variant of
      odontogenic tumor with ghost cells; only 29 cases are documented. Our patient was
      a 68-year-old man with a painless, well-defined, radiolucent swelling of the
      mandibular gingiva in the right incisor-to-molar region. It was diagnosed as a
      benign calcifying cystic odontogenic tumor (CCOT) on fenestration biopsy.
      Eighteen years later, he returned with swelling in the same area. The lesion was
      excised, diagnosed as GCOC, and considered a secondary malignant manifestation of
      the benign CCOT. No adjuvant chemotherapy or radiotherapy was administered, and
      his postoperative course was uneventful for 48 months, with no recurrence or
      distant metastasis. Among the 30 reported cases of GCOC, the mean age at
      diagnosis was 40.3 years, 22 (73%) involved the maxilla. Twelve (40%) were
      secondary malignant manifestations of benign CCOTs or dentinogenic ghost cell
      tumors. Five patients died of recurrence or distant metastasis.

PMID- 22862989
TI  - Nonsebaceous lymphadenoma of salivary gland: report of a case with
      immunohistochemistry and review of the literature.
AB  - OBJECTIVE: Nonsebaceous lymphadenomas are rare benign neoplasms. We emphasize the
      role of immunohistochemistry and attempt to elucidate the pathogenesis by
      investigating the distribution of 2 transcription factors, MYC and BLIMP1. STUDY
      DESIGN: A 70-year-old man was evaluated for a 3-cm left parotid mass. Ultrasound
      guided fine-needle aspiration biopsy findings were suggestive of a diagnosis of
      pleomorphic adenoma. A left superficial parotidectomy was performed, and based on
      histopathology a diagnosis of lymphadenoma, nonsebaceous type, was rendered.
      RESULTS: The tumor was positive for AE1/3, CKA, BclII, P63, CD79a, CD3, and MYC;
      focally positive for CK7 and epithelial membrane antigen; and negative for CD10,
      calponin, CD117, and BLIMP1. CONCLUSIONS: The rarity of nonsebaceous lymphadenoma
      and its superficial resemblance to commoner salivary gland tumors may present a
      diagnostic challenge for pathologists. The expression of MYC in the ductal
      component and the differentiation-related expression of PRDM1 in the superficial
      keratinizing layers point to a potential role for these 2 transcription factors
      in the pathogenesis of this neoplasm.

PMID- 22862990
TI  - Computed tomography fistulography demonstrating thyroglossal fistula: a case
      report.
AB  - We report a case of thyroglossal fistula in a young male that was clearly
      demonstrated using computed tomography fistulography.

PMID- 22862992
TI  - Genome-wide transcription factor gene prediction and their expressional tissue
      specificities in maize.
AB  - Transcription factors (TFs) are important regulators of gene expression. To
      better understand TF-encoding genes in maize (Zea mays L.), a genome-wide TF
      prediction was performed using the updated B73 reference genome. A total of 2298
      TF genes were identified, which can be classified into 56 families. The largest
      family, known as the MYB superfamily, comprises 322 MYB and MYB-related TF genes.
      The expression patterns of 2 014 (87.64%) TF genes were examined using RNA-seq
      data, which resulted in the identification of a subset of TFs that are
      specifically expressed in particular tissues (including root, shoot, leaf, ear,
      tassel and kernel). Similarly, 98 kernel-specific TF genes were further analyzed,
      and it was observed that 29 of the kernel-specific genes were preferentially
      expressed in the early kernel developmental stage, while 69 of the genes were
      expressed in the late kernel developmental stage. Identification of these TFs,
      particularly the tissue-specific ones, provides important information for the
      understanding of development and transcriptional regulation of maize.

PMID- 22862991
TI  - Exploring metazoan evolution through dynamic and holistic changes in protein
      families and domains.
AB  - BACKGROUND: Proteins convey the majority of biochemical and cellular activities
      in organisms. Over the course of evolution, proteins undergo normal sequence
      mutations as well as large scale mutations involving domain duplication and/or
      domain shuffling. These events result in the generation of new proteins and
      protein families. Processes that affect proteome evolution drive species
      diversity and adaptation. Herein, change over the course of metazoan evolution,
      as defined by birth/death and duplication/deletion events within protein families
      and domains, was examined using the proteomes of 9 metazoan and two outgroup
      species. RESULTS: In studying members of the three major metazoan groups, the
      vertebrates, arthropods, and nematodes, we found that the number of protein
      families increased at the majority of lineages over the course of metazoan
      evolution where the magnitude of these increases was greatest at the lineages
      leading to mammals. In contrast, the number of protein domains decreased at most
      lineages and at all terminal lineages. This resulted in a weak correlation
      between protein family birth and domain birth; however, the correlation between
      domain birth and domain member duplication was quite strong. These data suggest
      that domain birth and protein family birth occur via different mechanisms, and
      that domain shuffling plays a role in the formation of protein families. The
      ratio of protein family birth to protein domain birth (domain shuffling index)
      suggests that shuffling had a more demonstrable effect on protein families in
      nematodes and arthropods than in vertebrates. Through the contrast of high and
      low domain shuffling indices at the lineages of Trichinella spiralis and Gallus
      gallus, we propose a link between protein redundancy and evolutionary changes
      controlled by domain shuffling; however, the speed of adaptation among the
      different lineages was relatively invariant. Evaluating the functions of protein
      families that appeared or disappeared at the last common ancestors (LCAs) of the
      three metazoan clades supports a correlation with organism adaptation.
      Furthermore, bursts of new protein families and domains in the LCAs of metazoans
      and vertebrates are consistent with whole genome duplications. CONCLUSION:
      Metazoan speciation and adaptation were explored by birth/death and
      duplication/deletion events among protein families and domains. Our results
      provide insights into protein evolution and its bearing on metazoan evolution.

PMID- 22862993
TI  - Knowledge and attitudes towards complementary and alternative medicine among
      medical students in Turkey.
AB  - OBJECTIVE: This study aims to examine knowledge and attitudes towards
      Complementary and Alternative Medicine among medical students in Turkey, and find
      out whether they want to be trained in Complementary and Alternative Medicine
      (CAM). METHODS: A cross-sectional study was carried out between October and
      December 2010 among medical students. Data were collected from a total of seven
      medical schools. FINDINGS: The study included 943 medical students. The most well
      known methods among the students were herbal treatment (81.2 %), acupuncture
      (80.8 %), hypnosis (78.8 %), body-based practices including massage (77 %) and
      meditation (65.2 %), respectively. Acupuncture, aromatherapy, herbal treatment
      and meditation were better known among female participants compared to males (p <
      0.05). Females and first year students, generally had more positive attitudes. A
      larger proportion of female students compared to male students reported that a
      doctor should be knowledgeable about CAM (p = 0.001), and this knowledge would be
      helpful in their future professional lives (p = 0.015). Positive attitudes
      towards and willingness to receive training declined as the number of years spent
      in the faculty of medicine increased. CONCLUSIONS: Majority of the medical
      students were familiar with the CAM methods widely used in Turkey, while most of
      them had positive attitudes towards CAM as well as willingness to receive
      training on the subject, and they were likely to recommend CAM methods to their
      patients in their future professional lives. With its gradual scientific
      development and increasing popularity, there appears a need for a coordinated
      policy in integrating CAM into the medical curriculum, by taking expectations of
      and feedback from medical students into consideration in setting educational
      standards.

PMID- 22862994
TI  - Preventive therapy in children exposed to Mycobacterium tuberculosis: problems
      and solutions.
AB  - Young children living with a tuberculosis patient are at high risk of
      Mycobacterium tuberculosis infection and disease. WHO guidelines promote active
      screening and isoniazid (INH) preventive therapy (PT) for such children under 5
      years, yet this well-established intervention is seldom used in endemic
      countries. We review the literature regarding barriers to implementation of PT
      and find that they are multifactorial, including difficulties in screening, poor
      adherence, fear of increasing INH resistance and poor acceptability among primary
      caregivers and healthcare workers. These barriers are largely resolvable, and
      proposed solutions such as the adoption of symptom-based screening and shorter
      drug regimens are discussed. Integrated multicomponent and site-specific
      solutions need to be developed and evaluated within a public health framework to
      overcome the policy-practice gap and provide functional PT programmes for
      children in endemic settings.

PMID- 22862995
TI  - Melanoma back in the UVA spotlight.

PMID- 22862996
TI  - Recognition of a Caucasoid HLA-B locus allele, B*44:55, in a Taiwanese/Chinese
      bone marrow stem cell donor.
AB  - We detected a Caucasoid HLA-B allele, HLA-B*44:55, in a potential
      Taiwanese/Chinese bone marrow hematopoietic stem cell donor during our routine
      HLA SBT (sequence-based typing) practice. The sequence of B*44:55 varies with
      B*44:02:01:01 with one nucleotide in exon 2 at position 97 (T->C), while it
      differs from B*44:03:01 with one nucleotide in exon 2 at position 97 (T->C) and
      three nucleotides in exon 3 at residues 538-540 (CTG->GAC). The nucleotide
      replacements caused one amino acid variation with B*44:02:01:01 at residue 9 (Y
      >H) and two amino acid variations with B*44:03:01 at residue 9 (Y->H) and residue
      156 (L->D). The formation of B*44:55 is probably the result of a nucleotide
      substitution involving B*44:02:01:01 at position 97 (T->C). The Taiwanese/Chinese
      donor with B*44:55 claims having no kinship with Caucasian. Our speculations on
      the origin of the Taiwanese/Chinese B*44:55 will be presented.

PMID- 22862997
TI  - Risk factors of postoperative nosocomial pneumonia after resection of
      bronchogenic carcinoma.
AB  - BACKGROUND: Postoperative pneumonia following resection of bronchogenic carcinoma
      is a severe complication with a high rate of morbidity and mortality. The
      objective of this study is to determine the clinical and epidemiologic
      characteristics and the risk factors of postoperative pneumonia in patients
      undergoing resection of bronchogenic carcinoma in a third-level university
      hospital. METHODS: We performed a study of cases (with postoperative pneumonia)
      and controls (without pneumonia) nested in a prospective cohort of 604 patients
      who had undergone surgery for bronchogenic carcinoma in clinical stages I-IIIa
      between January 1999 and June 2004, where each case was grouped with 3 controls
      (3:1) of the same age (+/-5 years) and cancer staging by means of TNM
      classification. RESULTS: The incidence of postoperative pneumonia was 22 cases
      (3.6%). Overall in-hospital mortality of patients who underwent resection of
      bronchogenic carcinoma was 32 patients (5.3%). In-hospital mortality due to
      postoperative pneumonia was 7 cases (31.8%). In the postoperative pneumonia
      group, microorganisms were isolated in 10 cases (45.5%). The following factors
      appear in the multivariate analysis as statistically significant independent risk
      factors for postoperative pneumonia: body mass index <26.5 kg/m(2) (adjusted odds
      ratio (OR) per unit 0.64, 95% confidence interval (CI) 0.45-0.90, p = 0.011),
      predicted postoperative FEV(1) <50% pred. (adj. OR per unit 0.92, 95% CI 0.85
      0.99, p = 0.037), and reintubation after surgery (adj. OR 18.1, 95% CI 1.3-256.6,
      p = 0.032). CONCLUSIONS: Identifying the risk factors (some of which can by
      modified by medical intervention) may improve the course of lung cancer treated
      with surgery.

PMID- 22862998
TI  - Prospective application of clinician-performed lung ultrasonography during the
      2009 H1N1 influenza A pandemic: distinguishing viral from bacterial pneumonia.
AB  - BACKGROUND: Emergency department visits quadrupled with the initial onset and
      surge during the 2009 H1N1 influenza pandemic in New York City from April to June
      2009. This time period was unique in that >90% of the circulating virus was
      surveyed to be the novel 2009 H1N1 influenza A according to the New York City
      Department of Health. We describe our experience using lung ultrasound in a case
      series of patients with respiratory symptoms requiring chest X-ray during the
      initial onset and surge of the 2009 H1N1 influenza pandemic. METHODS: We describe
      a case series of patients from a prospective observational cohort study of lung
      ultrasound, enrolling patients requiring chest X-ray for suspected pneumonia that
      coincided with the onset and surge of the 2009 H1N1 influenza pandemic. RESULTS:
      Twenty pandemic 2009 H1N1 influenza patients requiring chest X-ray were enrolled
      during this time period. Median age was 6.7 years. Lung ultrasound via modified
      Bedside Lung Ultrasound in Emergency protocol assisted in the identification of
      viral pneumonia (n = 15; 75%), viral pneumonia with superimposed bacterial
      pneumonia (n = 7; 35%), isolated bacterial pneumonia only (n = 1; 5%), and no
      findings of viral or bacterial pneumonia (n = 4; 20%) in this cohort of patients.
      Based on 54 observations, interobserver agreement for distinguishing viral from
      bacterial pneumonia using lung ultrasound was K = 0.82 (0.63 to 0.99).
      CONCLUSIONS: Lung ultrasound may be used to distinguish viral from bacterial
      pneumonia. Lung ultrasound may be useful during epidemics or pandemics of acute
      respiratory illnesses for rapid point-of-care triage and management of patients.

PMID- 22862999
TI  - Social support and social strain in inter-episode bipolar disorder.
AB  - OBJECTIVES: This study focused on social support and social strain and their
      cross-sectional associations with instabilities in sleep and social rhythms in
      inter-episode bipolar disorder (BD). METHODS: Thirty-five adults diagnosed with
      inter-episode BD type I and 38 healthy controls completed measures of perceived
      social support and social strain. Group differences in support and strain were
      examined. Within the BD group, instabilities in sleep and social rhythms were
      assessed with 28 days of daily diary and actigraphy. Correlation and regression
      analyses were used to examine cross-sectional and prospective associations
      between social support, social strain, instabilities in sleep and social rhythms,
      and mood symptoms. RESULTS: The BD group reported lower social support and higher
      social strain than the control group. Additionally, social strain was positively
      correlated with manic and depressive symptoms in the BD group. Furthermore, there
      was a cross-sectional association between social support and more stable sleep on
      actigraphy in the BD group, although social support did not predict future sleep
      instability. CONCLUSIONS: These results indicate that inter-episode BD is
      associated with deficient social support and elevated social strain compared to
      controls, and that this may be due to persistent inter-episode mood symptoms.
      Social strain may be particularly important given its association with manic and
      depressive symptoms. The results also raise the possibility that sleep
      instability is related to poor social support in BD.

PMID- 22863000
TI  - Exposing secrets of telomere-telomerase encounters.
AB  - In order for telomeres to remain functional and stable, they must rendezvous with
      the enzyme telomerase in a productive manner. In human cells, this interaction is
      mediated by Cajal bodies as matchmaker, and now Zhong et al. reveal molecular
      determinants that establish good chemistry between the two partners.

PMID- 22863001
TI  - Thinking outside the synapse: glycine at extrasynaptic NMDA receptors.
AB  - In this issue, Papouin et al. show that glycine is the endogenous coagonist for
      extrasynaptic NMDA receptors (NMDARs), unlike at synapses where the coagonist is
      d-serine. By enzymatically degrading endogenous glycine, they begin to address
      the enigmatic physiological and pathological roles for extrasynaptic NMDARs.

PMID- 22863002
TI  - Host remodeling of the gut microbiome and metabolic changes during pregnancy.
AB  - Many of the immune and metabolic changes occurring during normal pregnancy also
      describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic
      syndrome in nonpregnant hosts. Here, to explore their role in pregnancy, we
      characterized fecal bacteria of 91 pregnant women of varying prepregnancy BMIs
      and gestational diabetes status and their infants. Similarities between infant
      mother microbiotas increased with children's age, and the infant microbiota was
      unaffected by mother's health status. Gut microbiota changed dramatically from
      first (T1) to third (T3) trimesters, with vast expansion of diversity between
      mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced
      richness. T3 stool showed strongest signs of inflammation and energy loss;
      however, microbiome gene repertoires were constant between trimesters. When
      transferred to germ-free mice, T3 microbiota induced greater adiposity and
      insulin insensitivity compared to T1. Our findings indicate that host-microbial
      interactions that impact host metabolism can occur and may be beneficial in
      pregnancy.

PMID- 22863003
TI  - TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to
      chromosome ends.
AB  - Telomere synthesis in cancer cells and stem cells involves trafficking of
      telomerase to Cajal bodies, and telomerase is thought to be recruited to
      telomeres through interactions with telomere-binding proteins. Here, we show that
      the OB-fold domain of the telomere-binding protein TPP1 recruits telomerase to
      telomeres through an association with the telomerase reverse transcriptase TERT.
      When tethered away from telomeres and other telomere-binding proteins, the TPP1
      OB-fold domain is sufficient to recruit telomerase to a heterologous chromatin
      locus. Expression of a minimal TPP1 OB-fold inhibits telomere maintenance by
      blocking access of telomerase to its cognate binding site at telomeres. We
      identify amino acids required for the TPP1-telomerase interaction, including
      specific loop residues within the TPP1 OB-fold domain and individual residues
      within TERT, some of which are mutated in a subset of pulmonary fibrosis
      patients. These data define a potential interface for telomerase-TPP1 interaction
      required for telomere maintenance and implicate defective telomerase recruitment
      in telomerase-related disease.

PMID- 22863005
TI  - Plasma membrane reshaping during endocytosis is revealed by time-resolved
      electron tomography.
AB  - Endocytosis, like many dynamic cellular processes, requires precise temporal and
      spatial orchestration of complex protein machinery to mediate membrane budding.
      To understand how this machinery works, we directly correlated fluorescence
      microscopy of key protein pairs with electron tomography. We systematically
      located 211 endocytic intermediates, assigned each to a specific time window in
      endocytosis, and reconstructed their ultrastructure in 3D. The resulting virtual
      ultrastructural movie defines the protein-mediated membrane shape changes during
      endocytosis in budding yeast. It reveals that clathrin is recruited to flat
      membranes and does not initiate curvature. Instead, membrane invagination begins
      upon actin network assembly followed by amphiphysin binding to parallel membrane
      segments, which promotes elongation of the invagination into a tubule. Scission
      occurs on average 9 s after initial bending when invaginations are ~100 nm deep,
      releasing nonspherical vesicles with 6,400 nm2 mean surface area. Direct
      correlation of protein dynamics with ultrastructure provides a quantitative 4D
      resource.

PMID- 22863004
TI  - The first five seconds in the life of a clathrin-coated pit.
AB  - Coated pits assemble by growth of a clathrin lattice, which is linked by adaptors
      to the underlying membrane. How does this process start? We used live-cell TIRF
      imaging with single-molecule EGFP sensitivity and high temporal resolution to
      detect arrival of the clathrin triskelions and AP2 adaptors that initiate coat
      assembly. Unbiased object identification and trajectory tracking, together with a
      statistical model, yield the arrival times and numbers of individual proteins, as
      well as experimentally confirmed estimates of the extent of substitution of
      endogenous by expressed, fluorescently tagged proteins. Pits initiate by
      coordinated arrival of clathrin and AP2, which is usually detected as two
      sequential steps, each of one triskelion with two adaptors. PI-4,5-P2 is
      essential for initiation. The accessory proteins FCHo1/2 are not; instead, they
      are required for sustained growth. This objective picture of coated pit
      initiation also shows that methods outlined here will be broadly useful for
      studies of dynamic assemblies in living cells.

PMID- 22863006
TI  - Dynamic assembly of brambleberry mediates nuclear envelope fusion during early
      development.
AB  - To accommodate the large cells following zygote formation, early blastomeres
      employ modified cell divisions. Karyomeres are one such modification, mitotic
      intermediates wherein individual chromatin masses are surrounded by nuclear
      envelope; the karyomeres then fuse to form a single mononucleus. We identified
      brambleberry, a maternal-effect zebrafish mutant that disrupts karyomere fusion,
      resulting in formation of multiple micronuclei. As karyomeres form, Brambleberry
      protein localizes to the nuclear envelope, with prominent puncta evident near
      karyomere-karyomere interfaces corresponding to membrane fusion sites.
      brambleberry corresponds to an unannotated gene with similarity to Kar5p, a
      protein that participates in nuclear fusion in yeast. We also demonstrate that
      Brambleberry is required for pronuclear fusion following fertilization in
      zebrafish. Our studies provide insight into the machinery required for karyomere
      fusion and suggest that specialized proteins are necessary for proper nuclear
      division in large dividing blastomeres.

PMID- 22863008
TI  - HSF1 drives a transcriptional program distinct from heat shock to support highly
      malignant human cancers.
AB  - Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response,
      facilitates malignant transformation, cancer cell survival, and proliferation in
      model systems. The common assumption is that these effects are mediated through
      regulation of heat-shock protein (HSP) expression. However, the transcriptional
      network that HSF1 coordinates directly in malignancy and its relationship to the
      heat-shock response have never been defined. By comparing cells with high and low
      malignant potential alongside their nontransformed counterparts, we identify an
      HSF1-regulated transcriptional program specific to highly malignant cells and
      distinct from heat shock. Cancer-specific genes in this program support oncogenic
      processes: cell-cycle regulation, signaling, metabolism, adhesion and
      translation. HSP genes are integral to this program, however, many are uniquely
      regulated in malignancy. This HSF1 cancer program is active in breast, colon and
      lung tumors isolated directly from human patients and is strongly associated with
      metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with
      prognostic and therapeutic implications.

PMID- 22863007
TI  - Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to
      DNA damage response signaling.
AB  - Nephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive
      diseases that affect kidney, retina, and brain. Genetic defects in NPHP gene
      products that localize to cilia and centrosomes defined them as "ciliopathies."
      However, disease mechanisms remain poorly understood. Here, we identify by whole
      exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC.
      All three genes function within the DNA damage response (DDR) pathway. We
      demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164,
      and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM
      at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes
      sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results
      in dysregulated DDR and an NPHP-RC phenotype. Our findings link degenerative
      diseases of the kidney and retina, disorders of increasing prevalence, to
      mechanisms of DDR.

PMID- 22863009
TI  - Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
AB  - Myc oncoproteins directly regulate transcription by binding to target genes, yet
      this only explains a fraction of the genes affected by Myc. mRNA turnover is
      controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs)
      found within many transcripts. Analyses of precancerous and malignant Myc
      expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED)
      genes and select AUBPs. Notably, Myc directly suppresses transcription of
      Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also
      operational during B lymphopoiesis and IL7 signaling. Importantly, TTP
      suppression is a hallmark of cancers with MYC involvement, and restoring TTP
      impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant
      state. Further, there is a selection for TTP loss in malignancy; thus, TTP
      functions as a tumor suppressor. Finally, Myc/TTP-directed control of select
      cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc
      targets AUBPs to regulate ARED genes that control tumorigenesis.

PMID- 22863010
TI  - Identification of regulators of polyploidization presents therapeutic targets for
      treatment of AMKL.
AB  - The mechanism by which cells decide to skip mitosis to become polyploid is
      largely undefined. Here we used a high-content image-based screen to identify
      small-molecule probes that induce polyploidization of megakaryocytic leukemia
      cells and serve as perturbagens to help understand this process. Our study
      implicates five networks of kinases that regulate the switch to polyploidy.
      Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased
      polyploidization, mature cell-surface marker expression, and apoptosis of
      malignant megakaryocytes. An integrated target identification approach employing
      proteomic and shRNA screening revealed that a major target of diMF is Aurora
      kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor
      of AURKA, induced polyploidization and expression of mature megakaryocyte markers
      in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL
      activity in vivo. Our findings provide a rationale to support clinical trials of
      MLN8237 and other inducers of polyploidization and differentiation in AMKL.

PMID- 22863011
TI  - Scl represses cardiomyogenesis in prospective hemogenic endothelium and
      endocardium.
AB  - Endothelium in embryonic hematopoietic tissues generates hematopoietic
      stem/progenitor cells; however, it is unknown how its unique potential is
      specified. We show that transcription factor Scl/Tal1 is essential for both
      establishing the hematopoietic transcriptional program in hemogenic endothelium
      and preventing its misspecification to a cardiomyogenic fate. Scl(-/-) embryos
      activated a cardiac transcriptional program in yolk sac endothelium, leading to
      the emergence of CD31+Pdgfralpha+ cardiogenic precursors that generated
      spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in
      Scl(-/-) hearts, where the disorganized endocardium precociously differentiated
      into cardiomyocytes. Induction of mosaic deletion of Scl in Scl(fl/fl)Rosa26Cre
      ER(T2) embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent
      cardiomyogenesis from endothelium. Scl(-/-) endothelium also upregulated the
      expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation
      of ectopic cardiogenic cells. These results reveal unexpected plasticity in
      embryonic endothelium such that loss of a single master regulator can induce
      ectopic cardiomyogenesis from endothelial cells.

PMID- 22863012
TI  - Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of
      Ppargamma.
AB  - Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like
      features in white adipose (WAT) is an attractive, if elusive, therapeutic
      approach to staunch the current obesity epidemic. Here we report that gain of
      function of the NAD-dependent deacetylase SirT1 or loss of function of its
      endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT
      by deacetylating peroxisome proliferator-activated receptor (Ppar)-gamma on
      Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required
      to recruit the BAT program coactivator Prdm16 to Ppargamma, leading to selective
      induction of BAT genes and repression of visceral WAT genes associated with
      insulin resistance. An acetylation-defective Ppargamma mutant induces a brown
      phenotype in white adipocytes, whereas an acetylated mimetic fails to induce
      "brown" genes but retains the ability to activate "white" genes. We propose that
      SirT1-dependent Ppargamma deacetylation is a form of selective Ppargamma
      modulation of potential therapeutic import.

PMID- 22863013
TI  - Synaptic and extrasynaptic NMDA receptors are gated by different endogenous
      coagonists.
AB  - N-methyl-d-aspartate receptors (NMDARs) are located in neuronal cell membranes at
      synaptic and extrasynaptic locations, where they are believed to mediate distinct
      physiological and pathological processes. Activation of NMDARs requires glutamate
      and a coagonist whose nature and impact on NMDAR physiology remain elusive. We
      report that synaptic and extrasynaptic NMDARs are gated by different endogenous
      coagonists, d-serine and glycine, respectively. The regionalized availability of
      the coagonists matches the preferential affinity of synaptic NMDARs for d-serine
      and extrasynaptic NMDARs for glycine. Furthermore, glycine and d-serine inhibit
      NMDAR surface trafficking in a subunit-dependent manner, which is likely to
      influence NMDARs subcellular location. Taking advantage of this coagonist
      segregation, we demonstrate that long-term potentiation and NMDA-induced
      neurotoxicity rely on synaptic NMDARs only. Conversely, long-term depression
      requires both synaptic and extrasynaptic receptors. Our observations provide key
      insights into the operating mode of NMDARs, emphasizing functional distinctions
      between synaptic and extrasynaptic NMDARs in brain physiology.

PMID- 22863015
TI  - SnapShot: endogenous RNAi machinery and mechanisms.

PMID- 22863014
TI  - A synthetic biology framework for programming eukaryotic transcription functions.
AB  - Eukaryotic transcription factors (TFs) perform complex and combinatorial
      functions within transcriptional networks. Here, we present a synthetic framework
      for systematically constructing eukaryotic transcription functions using
      artificial zinc fingers, modular DNA-binding domains found within many eukaryotic
      TFs. Utilizing this platform, we construct a library of orthogonal synthetic
      transcription factors (sTFs) and use these to wire synthetic transcriptional
      circuits in yeast. We engineer complex functions, such as tunable output strength
      and transcriptional cooperativity, by rationally adjusting a decomposed set of
      key component properties, e.g., DNA specificity, affinity, promoter design,
      protein-protein interactions. We show that subtle perturbations to these
      properties can transform an individual sTF between distinct roles (activator,
      cooperative factor, inhibitory factor) within a transcriptional complex, thus
      drastically altering the signal processing behavior of multi-input systems. This
      platform provides new genetic components for synthetic biology and enables bottom
      up approaches to understanding the design principles of eukaryotic
      transcriptional complexes and networks.

PMID- 22863016
TI  - A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected
      autologous T cells for recurrent ovarian cancer.
AB  - PURPOSE: In spite of increased rates of complete response to initial
      chemotherapy, most patients with advanced ovarian cancer relapse and succumb to
      progressive disease. RATIONALE: Genetically reprogrammed, patient-derived
      chimeric antigen receptor (CAR)-T lymphocytes with the ability to recognize
      predefined surface antigens with high specificity in a non-MHC restricted manner
      have shown increasing anti-tumor efficacy in preclinical and clinical studies.
      Folate receptor-alpha (FRalpha) is an ovarian cancer-specific tumor target;
      however, it is expressed at low levels in certain organs with risk for toxicity.
      DESIGN: Here we propose a phase I study testing the feasibility, safety and
      preliminary activity of FRalpha-redirected CAR-T cells bearing the CD137 (4-1BB)
      costimulatory domain, administered after lymphodepletion for the treatment of
      recurrent ovarian cancer. A novel trial design is proposed that maximizes safety
      features. INNOVATION: This design involves an initial accelerated dose escalation
      phase of FR-alpha CAR-T cells followed by a standard 3 + 3 escalation phase. A
      split-dose approach is proposed to mitigate acute adverse events. Furthermore,
      infusion of bulk untransduced autologous peripheral blood lymphocytes (PBL) is
      proposed two days after CAR-T cell infusion at the lower dose levels of CAR-T
      cells, to suppress excessive expansion of CAR-T cells in vivo and mitigate
      toxicity.

PMID- 22863017
TI  - Respite: carers' experiences and perceptions of respite at home.
AB  - BACKGROUND: Informal carers play an important role in supporting people with long
      term conditions living at home. However, the caring role is known to have adverse
      effects on carers such as poorer emotional health and social isolation. A variety
      of types of respite may be offered to carers but little is known about the
      benefits of respite, carers' experiences with it, or their perceptions of care
      workers. This study therefore investigated these experiences and perceptions.
      METHOD: Recorded, semi-structured interviews were undertaken with twelve carers
      receiving weekly four-hourly respite. Carers were either caring for a person over
      sixty or were over sixty themselves. Interviews were analysed thematically.
      RESULTS AND DISCUSSION: Respite sometimes alleviated carers' constant sense of
      responsibility for their cared for. Trust, whether in the service provider or
      individual care workers, was essential. Carers lacking this trust tended to
      perceive respite as less beneficial. Low expectations were common with carers
      often unwilling to find fault. Care workers were frequently seen as very kind
      with some carers valuing their company. Care workers who were flexible,
      communicated well and responded to the cared for's needs were valued. Stimulation
      of the cared for during respite was very important to most carers but the
      perceived benefits for carers were often very individual. Many carers used
      respite to catch up with routine, domestic tasks, rarely using it to socialise.
      CONCLUSIONS: For many carers, respite was a way of maintaining normality in often
      difficult, restricted lives. Respite allowed continuation of what most people
      take for granted. Carers frequently viewed respite as intended to improve their
      cared for's quality of life, rather than their own. This centrality of the cared
      for means that carers can only really benefit from respite if the cared for is
      happy and also seen to benefit. Future research should investigate the
      perspectives of carers and their cared for, focussing on different demographic
      groups by features such as age, gender, ethnicity and diagnostic groups. However,
      without greater clarity about what respite is intended to achieve, clear evidence
      of a positive impact of this intervention may remain difficult to identify.

PMID- 22863018
TI  - Evaluation of the use of induced pluripotent stem cells (iPSCs) for the
      regeneration of tracheal cartilage.
AB  - The treatment of laryngotracheal stenosis remains a challenge as treatment often
      requires multistaged procedures, and successful decannulation sometimes fails
      after a series of operations. Induced pluripotent stem cells (iPSCs) were
      generated in 2006. These cells are capable of unlimited  symmetrical self
      renewal, thus providing an unlimited cell source for tissue-engineering
      applications. We have previously reported tracheal wall regeneration using a
      three-dimensional (3D) scaffold containing iPSCs. However, the efficiency of
      differentiation into cartilage was low. In addition,  it could not be proven that
      the cartilage tissues were in fact derived from the implanted iPSCs. The purpose
      of this study was to evaluate and improve the use of iPSCs for the regeneration
      of tracheal cartilage. iPSCs were cultured in vitro in a 3D scaffold in
      chondrocyte differentiation medium.  After cultivation, differentiation into
      chondrocytes was examined. The ratio of undifferentiated cells was analyzed by
      flow cytometry. The 3D scaffolds were implanted into tracheal defects, as an
      injury site, in 24 nude rats. Differentiation into chondrocytes in vitro was
      confirmed histologically,  phenotypically, and genetically. Flow cytometric
      analysis demonstrated that the population of undifferentiated cells was
      decreased. Cartilage tissue was observed in the regenerated tracheal wall in 6 of
      11 rats implanted with induced iPSCs, but in none of 13 rats implanted with the
      control  and noninduced iPSCs. The expression of cartilage-specific protein was
      also demonstrated in vivo in 3D scaffolds containing iPSCs. The presence of the
      GFP gene derived from iPSCs was confirmed in samples of cartilage tissue by the
      combination of laser microdissection (LMD) and polymerase chain  reaction (PCR)
      techniques. Our study demonstrated that iPSCs have the potential to differentiate
      into chondrogenic cells in vitro. Cartilage tissue was regenerated in vivo. Our
      results suggest that iPSCs could be a new cell source for the regeneration of
      tracheal cartilage.

PMID- 22863019
TI  - Fluid shear stress regulates metalloproteinase-1 and 2 in human periodontal
      ligament cells: involvement of extracellular signal-regulated kinase (ERK) and
      P38 signaling pathways.
AB  - Matrix metalloproteinase (MMP)-1, 2, with their endogenous inhibitors, tissue
      inhibitor of metalloproteinase (TIMP)-1, 2 are critical for extracellular matrix
      remodeling in human periodontal ligament (PDL) and their expression are sensitive
      to mechanical stresses. Shear stress as the main type of mechanical stress in
      tooth movement is involved in matrix turnover. However, how shear stress
      regulates MMPs and TIMPs system is still unclear. In this study, we investigated
      the effect of fluid shear stress on expression of MMP-1, 2 and TIMP-1, 2 in human
      PDL cells and the possible roles of mitogen-activated protein kinases in this
      process. Three levels of fluid shear stresses (6, 9 and 12 dyn/cm(2)) were loaded
      on PDL cells for 2, 4, 8 and 12h. The results indicated that fluid shear stress
      rearranged cytoskeleton in PDL cells. Fluid shear stress increased expression of
      MMP-1, 2, TIMP-1 and suppressed TIMP-2 expression. MAP kinases including
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and
      p38 were activated rapidly by fluid shear stress. The ERK inhibitor blocked fluid
      shear stress induced MMP-1 expression and P38 inhibitor reduced fluid shear
      stress stimulated MMP-2 expression. Our study suggested that fluid shear stress
      involved in PDL remodeling via regulating MMP-1, 2 and TIMP-1, 2 expression. ERK
      regulated fluid shear stress induced MMP-1 expression and P38 play a role in
      fluid shear stress induced MMP-2 upregulation.

PMID- 22863020
TI  - Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both
      mutant and wild-type epidermal growth factor receptors.
AB  - Somatic mutations in the epidermal growth factor receptor (EGFR) gene, such as
      exon 19 deletion mutations, are important factors in determining therapeutic
      responses to gefitinib in non-small-cell lung cancer (NSCLC). However, some
      patients have activating mutations in EGFR and show poor responses to gefitinib.
      In this study, we examined three NSCLC cell lines, HCC827, PC9, and HCC2935, that
      expressed an EGFR exon 19 deletion mutation. All cells expressed mutant EGFR, but
      the PC9 and HCC2935 cells also expressed wild-type EGFR. The HCC827 cells were
      highly sensitive to gefitinib under both normoxia and hypoxia. However, the PC9
      and HCC2935 cells were more resistant to gefitinib under hypoxic conditions
      compared to normoxia. Phosphorylation of EGFR and ERK was suppressed with
      gefitinib treatment to a lesser extent under hypoxia. The expression of
      transforming growth factor-alpha (TGFalpha) was dramatically upregulated under
      hypoxia, and the knockdown of TGFalpha or hypoxia-inducible factor-1alpha
      (HIF1alpha) reversed the resistance to gefitinib in hypoxic PC9 and HCC2935
      cells. Finally, introduction of the wild-type EGFR gene into the HCC827 cells
      caused resistance to gefitinib under hypoxia. This phenomenon was also reversed
      by the knockdown of TGFalpha or HIF1alpha. Our results indicate that hypoxia
      causes gefitinib resistance in EGFR-mutant NSCLC through the activation of wild
      type EGFR mediated by the upregulation of TGFalpha. The presence of wild-type and
      mutant EGFR along with tumor hypoxia are important factors that should be
      considered when treating NSCLC patients with gefitinib.

PMID- 22863021
TI  - A comparison of two treatments for childhood apraxia of speech: methods and
      treatment protocol for a parallel group randomised control trial.
AB  - BACKGROUND: Childhood Apraxia of Speech is an impairment of speech motor planning
      that manifests as difficulty producing the sounds (articulation) and melody
      (prosody) of speech. These difficulties may persist through life and are
      detrimental to academic, social, and vocational development. A number of
      published single subject and case series studies of speech treatments are
      available. There are currently no randomised control trials or other well
      designed group trials available to guide clinical practice. METHODS/DESIGN: A
      parallel group, fixed size randomised control trial will be conducted in Sydney,
      Australia to determine the efficacy of two treatments for Childhood Apraxia of
      Speech: 1) Rapid Syllable Transition Treatment and the 2) Nuffield Dyspraxia
      Programme - Third edition. Eligible children will be English speaking, aged 4-12
      years with a diagnosis of suspected CAS, normal or adjusted hearing and vision,
      and no comprehension difficulties or other developmental diagnoses. At least 20
      children will be randomised to receive one of the two treatments in parallel.
      Treatments will be delivered by trained and supervised speech pathology
      clinicians using operationalised manuals. Treatment will be administered in 1
      hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech
      sound and prosodic accuracy on a customised 292 item probe and the Diagnostic
      Evaluation of Articulation and Phonology inconsistency subtest administered prior
      to treatment and 1 week, 1 month and 4 months post-treatment. All post
      assessments will be completed by blinded assessors. Our hypotheses are: 1)
      treatment effects at 1 week post will be similar for both treatments, 2)
      maintenance of treatment effects at 1 and 4 months post will be greater for Rapid
      Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3)
      generalisation of treatment effects to untrained related speech behaviours will
      be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia
      Programme treatment. This protocol was approved by the Human Research Ethics
      Committee, University of Sydney (#12924). DISCUSSION: This will be the first
      randomised control trial to test treatment for CAS. It will be valuable for
      clinical decision-making and providing evidence-based services for children with
      CAS. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12612000744853.

PMID- 22863022
TI  - Development of a porcine (Sus scofa) embryo-specific microarray: array annotation
      and validation.
AB  - BACKGROUND: The domestic pig is an important livestock species and there is
      strong interest in the factors that affect the development of viable embryos and
      offspring in this species. A limited understanding of the molecular mechanisms
      involved in early embryonic development has inhibited our ability to fully
      elucidate these factors. Next generation deep sequencing and microarray
      technologies are powerful tools for delineation of molecular pathways involved in
      the developing embryo. RESULTS: Here we present the development of a porcine
      embryo-specific microarray platform created from a large expressed sequence tag
      (EST) analysis generated by Roche/454 next-generation sequencing of cDNAs
      constructed from critical stages of in vivo or in vitro porcine preimplantation
      embryos. Two cDNA libraries constructed from in vitro and in vivo produced
      preimplantation porcine embryos were normalized and sequenced using 454 Titanium
      pyrosequencing technology. Over one million high-quality EST sequences were
      obtained and used to develop the EMbryogene Porcine Version 1 (EMPV1) microarray
      composed of 43,795 probes. Based on an initial probe sequence annotation, the
      EMPV1 features 17,409 protein-coding, 473 pseudogenes, 46 retrotransposed, 2,359
      non-coding RNA, 4,121 splice variants in 2,862 genes and a total of 12,324 Novel
      Transcript Regions (NTR). After re-annotation, the total unique genes increased
      from 11,961 to 16,281 and 1.9% of them belonged to a large olfactory receptor
      (OR) gene family. Quality control on the EMPV1 was performed and revealed an even
      distribution of ten clusters of spiked-in control spots and array to array (dye
      swap) correlation was 0.97. CONCLUSIONS: Using next-generation deep sequencing we
      have produced a large EST dataset to allow for the selection of probe sequences
      for the development of the EMPV1 microarray platform. The quality of this embryo
      specific array was confirmed with a high-level of reproducibility using current
      Agilent microarray technology. With more than an estimated 20,000 unique genes
      represented on the EMPV1, this platform will provide the foundation for future
      research into the in vivo and in vitro factors that affect the viability of
      porcine embryos, as well as the effects of these factors on the live offspring
      that result from these embryos.

PMID- 22863024
TI  - Point-of-care ultrasound used to exclude penile fracture.
AB  - This is a case report of a superficial penile hematoma that was difficult to
      distinguish clinically from a penile fracture. Such cases occur with relative
      frequency, and because definitive treatment is an urgent surgery, timely
      diagnosis is essential to avoid complications. Typical imaging modalities such as
      cavernosonography and magnetic resonance imaging can be invasive
      (cavernosonography) or time consuming (magnetic resonance imaging) and may not be
      readily available. Ultrasound has been used successfully in such cases, and, in
      this case, we used point-of-care ultrasound combined with a brief period of
      observation to exclude penile fracture.

PMID- 22863023
TI  - Use of palliative radiotherapy in brain and bone metastases (VARA II study).
AB  - INTRODUCTION: Metastases are detected in 20% of patients with solid tumours at
      diagnosis and a further 30% after diagnosis. Radiation therapy (RT) has proven
      effective in bone (BM) and brain (BrM) metastases. The objective of this study
      was to analyze the variability of RT utilization rates in clinical practice and
      the accessibility to medical technology in our region. PATIENTS AND METHODS: We
      reviewed the clinical records and RT treatment sheets of all patients undergoing
      RT for BM and/or BrM during 2007 in the 12 public hospitals in an autonomous
      region of Spain. Data were gathered on hospital type, patient type and RT
      treatment characteristics. Calculation of the rate of RT use was based on the
      cancer incidence and the number of RT treatments for BM, BrM and all cancer
      sites. RESULTS: Out of the 9319 patients undergoing RT during 2007 for cancer at
      any site, 1242 (13.3%; inter-hospital range, 26.3%) received RT for BM (n = 744)
      or BrM (n = 498). These 1242 patients represented 79% of all RT treatments with
      palliative intent, and the most frequent primary tumours were in lung, breast,
      prostate or digestive system. No significant difference between BM and BrM groups
      were observed in: mean age (62 vs. 59 yrs, respectively); gender (approximately
      64% male and 36% female in both); performance status (ECOG 0-1 in 70 vs. 71%); or
      mean distance from hospital (36 vs. 28.6 km) or time from consultation to RT
      treatment (13 vs. 14.3 days). RT regimens differed among hospitals and between
      patient groups: 10 * 300 cGy, 5 * 400 cGy and 1x800cGy were applied in 32, 27 and
      25%, respectively, of BM patients, whereas 10 * 300cGy was used in 49% of BrM
      patients. CONCLUSIONS: Palliative RT use in BM and BrM is high and close to the
      expected rate, unlike the global rate of RT application for all cancers in our
      setting. Differences in RT schedules among hospitals may reflect variability in
      clinical practice among the medical teams.

PMID- 22863025
TI  - Paracetamol degradation intermediates and toxicity during photo-Fenton treatment
      using different iron species.
AB  - The photo-Fenton degradation of paracetamol (PCT) was evaluated using FeSO(4) and
      the iron complex potassium ferrioxalate (FeOx) as iron source under simulated
      solar light. The efficiency of the degradation process was evaluated considering
      the decay of PCT and total organic carbon concentration and the generation of
      carboxylic acids, ammonium and nitrate, expressed as total nitrogen. The results
      showed that the degradation was favored in the presence of FeSO(4) in relation to
      FeOx. The higher concentration of hydroxylated intermediates generated in the
      presence of FeSO(4) in relation to FeOx probably enhanced the reduction of
      Fe(III) to Fe(II) improving the degradation efficiency. The degradation products
      were determined using liquid chromatography electrospray time-of-flight mass
      spectrometry. Although at different concentrations, the same intermediates were
      generated using either FeSO(4) or FeOx, which were mainly products of
      hydroxylation reactions and acetamide. The toxicity of the sample for Vibrio
      fischeri and Daphnia magna decreased from 100% to less than 40% during photo
      Fenton treatment in the presence of both iron species, except for D. magna in the
      presence of FeOx due to the toxicity of oxalate to this organism. The
      considerable decrease of the sample toxicity during photo-Fenton treatment using
      FeSO(4) indicates a safe application of the process for the removal of this
      pharmaceutical.

PMID- 22863026
TI  - Spectroscopic study of degradation products of ciprofloxacin, norfloxacin and
      lomefloxacin formed in ozonated wastewater.
AB  - This study addressed the formation and properties of degradation products of
      ciprofloxacin, norfloxacin and lomefloxacin formed during ozonation of secondary
      wastewater effluent containing these fluoroquinolone antibiotics. The generation
      of the degradation products was interpreted in the context of transformations of
      effluent organic matter (EfOM) tracked via absorbance measurements. The
      structures of 20 degradation products were elucidated for ciprofloxacin and
      norfloxacin, respectively. 27 degradation products were identified for
      lomefloxacin. The prevalent oxidation pathways were suggested based on the
      structures of the identified products formed in the absence and presence of the
      hydroxyl radical scavenger t-butanol. These pathways were largely similar for all
      studied fluoroquinolones and involved attacks on the piperazine ring and the
      quinolone structure. The quinolone ring remained intact in the presence of t
      butanol thus indicating that this functional group could only be oxidized by OH
      radicals while the piperazine ring was readily oxidized by molecular ozone. The
      cleavage of the quinolone moiety that resulted in several identified degradation
      products occurred via the attack by hydroxyl radicals on the carbon-carbon double
      bond adjacent to the carboxylic acid group. Lomefloxacin had more diverse
      oxidation products due to the presence of a methyl group on its piperazinyl ring.
      The concentrations of the identified degradation products behaved non
      monotonically as a function of ozone dose or treatment time, yet exhibited
      interpretable correlations versus changes of EfOM absorbance. Examination of
      these correlations allowed developing a novel approach for elucidating the
      transformations of fluoroquinolone antibiotics during ozonation.

PMID- 22863027
TI  - Impact of water treatment on the contribution of faucets to dissolved and
      particulate lead release at the tap.
AB  - A field study was performed in a building complex to investigate the extent and
      sources of lead (Pb) release in tap water and brass material was found to be the
      main contributor in the very first draw (250 mL). Based on these results, a pilot
      installation was built to study Pb leaching from old and new faucets in the
      presence and absence of a connection to Cu piping. Four water quality conditions
      were tested: i) no treatment; ii) addition of 0.8 mg P/L of orthophosphate; iii)
      pH adjustment to 8.4; and iv) adjustment to a higher chloride to sulfate mass
      ratio (CSMR; ratio from 0.3 to 2.9). Pb concentrations in samples taken from the
      faucets without treatment ranged from 1 to 52 MUg/L, with a mean of 11 MUg/L. The
      addition of orthophosphate @ 0.8 mg P/L (OrthoP) was the most effective treatment
      for all types of faucets tested. On average, OrthoP reduced mean Pb leaching by
      41%, and was especially effective for new double faucets (70%). In the presence
      of orthophosphates, the relative proportion of particulate Pb (Pbpart) (>0.45
      MUm) increased from 31% to 54%. However, OrthoP was not efficient to reduce Zn
      release. The higher CSMR condition was associated with greater dezincification of
      yellow brass but not of red brass. Corrosion control treatment influenced Pb
      concentration equilibrium, directly impacting maximal exposure. Significantly
      higher Pb release (3 fold) was observed for 1 of the 8 faucets connected to Cu
      exposed to high CSMR water, suggesting the presence of galvanic corrosion.

PMID- 22863028
TI  - Review article: use of induction therapy in liver transplantation.
AB  - Induction therapy is used relatively infrequently in liver transplantation, but
      developments in induction regimens and strategies for their use are prompting a
      re-examination of its benefits. Rabbit antithymocyte globulin (rATG) induces
      protracted, dose-dependent lymphocytopenia with preferential reconstitution of
      regulatory T-lymphocytes. Non-depleting interleukin-2 receptor antagonists (IL
      2RA) act selectively on activated T-lymphocytes with a shorter duration of
      effect. IL-2RA induction with delayed and reduced calcineurin inhibitor (CNI)
      exposure appears to preserve efficacy, while more aggressive CNI minimisation has
      been attempted successfully using rATG. Steroid-free tacrolimus monotherapy with
      rATG or IL-2RA induction is effective if adequate tacrolimus exposure is
      maintained. Early concerns that addition of induction to a conventional
      maintenance regimen could lead to accelerated progression of hepatitis C disease,
      or to an increased risk of hepatocellular cancer recurrence, now appear unfounded
      using modern regimens. Similarly, with routine use of systemic prophylaxis,
      recent prospective and retrospective data have not shown a higher rate of
      infections overall, or cytomegalovirus infection specifically, using rATG or IL
      2RA induction. Historical evidence that lymphocyte-depleting agents increased the
      risk of non-Hodgkin lymphoma has not been confirmed for rATG. Wider use of
      induction in liver transplantation is now merited, using individualized
      strategies to support reduced CNI exposure or steroid-free immunosuppression.

PMID- 22863029
TI  - Enteric-coated mycophenolate sodium immunosuppression in renal transplant
      patients: efficacy and dosing.
AB  - Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) formulation, has improved
      both short- and long-term outcomes following renal transplantation, but is often
      associated with gastrointestinal (GI) complications that can lead to dose
      reduction or discontinuation, potentially jeopardizing patient outcomes. Enteric
      coated mycophenolate sodium (EC-MPS) delivers equivalent MPA exposure to MMF and
      offers the potential to reduce GI burden (while maintaining patient safety). Here
      we review the efficacy of EC-MPS compared with MMF in renal transplant patients
      in terms of biopsy-proven acute rejection and graft loss, and examine the use of
      EC-MPS in newer regimens such as intensified dosing and calcineurin inhibitor
      minimization.

PMID- 22863030
TI  - Prevalence and determinants of misreporting among European children in proxy
      reported 24 h dietary recalls.
AB  - Dietary assessment is strongly affected by misreporting (both under- and over
      reporting), which results in measurement error. Knowledge about misreporting is
      essential to correctly interpret potentially biased associations between diet and
      health outcomes. In young children, dietary data mainly rely on proxy respondents
      but little is known about determinants of misreporting here. The present analysis
      was conducted within the framework of the multi-centre IDEFICS (Identification
      and prevention of dietary- and lifestyle-induced health effects in children and
      infants) study and is based on 6101 children aged 2-9 years with 24 h dietary
      recall (24-HDR) and complete covariate information. Adapted Goldberg cut-offs
      were applied to classify the 24-HDR as 'over-report', 'plausible report' or
      'under-report'. Backward elimination in the course of multi-level logistic
      regression analyses was conducted to identify factors significantly related to
      under- and over-reporting. Next to characteristics of the children and parents,
      social factors and parental concerns/perceptions concerning their child's weight
      status were considered. Further selective misreporting was addressed,
      investigating food group intakes commonly perceived as more or less socially
      desirable. Proportions of under-, plausible and over-reports were 8.0, 88.6 and
      3.4 %, respectively. The risk of under-reporting increased with age (OR 1.19, 95
      % CI 1.05, 1.83), BMI z-score of the child (OR 1.23, 95 % CI 1.10, 1.37) and
      household size (OR 1.12, 95 % CI 1.01, 1.25), and was higher in low/medium income
      groups (OR 1.45, 95 % CI 1.13, 1.86). Over-reporting was negatively associated
      with BMI z-scores of the child (OR 0.78, 95 % CI 0.69, 0.88) and higher in girls
      (OR 1.70, 95 % CI 1.27, 2.28). Further social desirability and parental
      concerns/perceptions seemed to influence the reporting behaviour. Future studies
      should involve these determinants of misreporting when investigating diet-disease
      relationships in children to correct for the differential reporting bias.

PMID- 22863031
TI  - White matter integrity within the corpus callosum differentiates late-life
      bipolar and unipolar depression.

PMID- 22863032
TI  - Coordinating genome expression with cell size.
AB  - Cell size is highly variable; cells from various tissues differ in volume over
      orders of magnitudes, from tiny lymphocytes to giant neurons, and cells of a
      given type change size during the cell cycle. Larger cells need to produce and
      maintain higher amounts of RNA and protein to sustain biomass and function,
      although the genome content often remains constant. Available data indicate that
      the transcriptional and translational outputs scale with cell size at a genome
      wide level, but how such remarkably coordinated regulation is achieved remains
      largely mysterious. With global and systems-level approaches becoming more
      widespread and quantitative, it is worth revisiting this fascinating problem.
      Here, we outline current knowledge of the fundamental relations between genome
      regulation and cell size, and highlight the biological implications and potential
      mechanisms of the global tuning of gene expression to cellular volume.

PMID- 22863034
TI  - Limited referral to nephrologists from a tertiary geriatric outpatient clinic
      despite a high prevalence of chronic kidney disease and anaemia.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasing in prevalence world-wide
      with the largest growth being in the elderly. The aim of this study was to
      examine the prevalence of CKD in a geriatric outpatient clinic within a tertiary
      hospital and its association with anaemia and mortality with a focus on the
      referral patterns towards nephrologists. METHODS: Retrospective study utilising
      administrative databases. The cohort was defined as all patients that attended
      the geriatric outpatient clinics of a single tertiary hospital within the first 3
      months of 2006. Patients were followed for 18 months for mortality and referral
      to a nephrologist. RESULTS: The mean Glomerular filtration rate (eGFR) of the 439
      patients was 67.4 +/- 29.1 mL/min/1.73 m2 (44% <60 mL/min/1.73 m2). 11.8% had a
      haemoglobin < 110 g/L, with anaemia being significantly associated with kidney
      function in those with a eGFR < 60 mL/min/1.73 m2 (p = 0.0092). Kidney function
      and anaemia were significantly associated with mortality on multivariate analysis
      (p = 0.019 and p = 0.0074). After 18 months, 8.8% of patients with CKD were
      referred to a nephrologist. CONCLUSION: Despite a high prevalence of CKD in
      patients attending a geriatric outpatient clinic and its association with anaemia
      and mortality, few of these patients were referred to a nephrologist. An
      examination of the reasons behind this bias is required.

PMID- 22863035
TI  - Simple questionnaire and urine reagent strips compared to microscopy for the
      diagnosis of Schistosoma haematobium in a community in northern Ghana.
AB  - OBJECTIVES: To evaluate the utility of a simple questionnaire and urine reagent
      strip testing for the rapid diagnosis of Schistosoma haematobium in rural
      northern Ghana. METHODS: Cross-sectional parasitological and questionnaire survey
      in a community in northern Ghana. Participants provided two urine specimens that
      were examined under a microscope using a centrifugation method. The first urine
      sample was additionally subjected to reagent strip testing. A short questionnaire
      was administered to all participants. RESULTS: Microscopy of urine samples
      obtained from 208 individuals aged 1-77 years revealed an S. haematobium
      prevalence of 6.8%. The presence of any blood or protein on a urine reagent strip
      was 100% and 42% sensitive, and 93% and 80% specific for S. haematobium
      diagnosis. Questionnaires were completed by 198 individuals. Self-reported
      haematuria showed a sensitivity of 53% and a specificity of 85%. A dichotomous
      two-question panel was helpful in S. haematobium diagnosis, with working and
      playing near the river significantly associated with S. haematobium infection (P
      < 0.001). CONCLUSION: The use of urine reagent strips, coupled with questions
      pertaining to water contact patterns, might be considered for point-of-contact
      diagnosis of S. haematobium where microscopy is unavailable.

PMID- 22863036
TI  - Cell culture model predicts human disease: Altered expression of junction
      proteins and matrix metalloproteinases in cervical dysplasia.
AB  - BACKGROUND: Cervical cancer is necessarily caused by human papillomaviruses,
      which encode three oncogenes manifesting their functions by interfering with a
      number of cellular proteins and pathways: the E5, E6, and E7 proteins. We have
      earlier found in our microarray studies that the E5 oncogene crucially affects
      the expression of cellular genes involved in adhesion and motility of epithelial
      cells. METHODS: In order to biologically validate our previous experimental
      findings we performed immunohistochemical staining of a representative set of
      tissue samples from different grades of high-risk human papillomavirus associated
      cervical disease as well as normal squamous and columnar cervical epithelium.
      Three-dimensional collagen raft cultures established from E5-expressing and
      control epithelial cells were also examined. The expression of p16, matrix
      metalloproteinase (MMP) -7, MMP-16, cytokeratin (CK) 8/18, laminin, E-cadherin
      and beta-catenin was studied. RESULTS: In agreement with our previous microarray
      studies, we found intense staining for E-cadherin and beta-catenin in adherens
      junctions even in high-grade cervical lesions. Staining for MMP-16 was increased
      in severe disease as well. No significant change in staining for MMP-7 and
      cytokeratin 8/18 along with the grade of cervical squamous epithelial disease was
      observed. CONCLUSIONS: Here we have confirmed, using tissue material from human
      papillomavirus associated lesions, some of the cellular gene expression
      modifications that we earlier reported in an experimental system studying
      specifically the E5 oncogene of papillomaviruses. These findings were partially
      surprising in the context of cervical carcinogenesis and emphasize that the
      complexity of carcinogenesis is not yet fully understood. Microarray approaches
      provide a wide overwiev of gene expression in experimental settings, which may
      yield biologically valid biomarkers for disease diagnostics, prognosis, and
      follow-up.

PMID- 22863037
TI  - Analysis of human liver disease using a cluster of differentiation (CD) antibody
      microarray.
AB  - BACKGROUND: A CD antibody microarray has been previously developed allowing semi
      quantitative identification of greater than 80 CD antigens on circulating
      leucocytes from peripheral blood samples. This assay, which uses a live cell
      capture technique, enables an extensive leucocyte immunophenotype determination
      in a single analysis and to date this has been used successfully to characterise
      diseases including human leukaemias and HIV infection. AIMS: To determine CD
      antigen expression profiles for patients with various liver diseases and to look
      for preserved disease-specific signatures. METHODS: Three liver disease groups
      including hepatitis C (HCV) (n = 35), non-alcoholic steatohepatitis (NASH) (n =
      21) and alcohol-related liver disease (n = 14) were compared with a normal group
      (n = 23). Hierarchal Clustering (HCL) and Principal Component Analysis (PCA) of
      the data revealed distinct binding patterns for patients with and without
      cirrhosis. RESULTS: Patients with cirrhosis and portal hypertension compared with
      those without cirrhosis had significantly reduced expression of several markers
      of T-cell function including CD45, CD8, CD28 and TCR alpha/beta. Disease
      prediction algorithms based on the expression data were able to discriminate
      cirrhotics from non-cirrhotics with 71% overall success, which improved to 77%
      when only patients with HCV were considered. CONCLUSIONS: These results
      demonstrate disease-specific consensus patterns of expression of CD antigens for
      patients with chronic liver disease, suggesting that the CD antibody array is a
      promising tool in the analysis of human liver disease, and with further
      refinement may have future research and clinical utility.

PMID- 22863038
TI  - The emperor's new framework for mental health in England.

PMID- 22863039
TI  - Pulling the plug on drug detention centres in Asia.

PMID- 22863040
TI  - Meeting global needs in primary care with nurse practitioners.

PMID- 22863043
TI  - Hepatocellular carcinoma.

PMID- 22863044
TI  - Hepatocellular carcinoma.

PMID- 22863045
TI  - Hepatocellular carcinoma.

PMID- 22863046
TI  - Hepatocellular carcinoma.

PMID- 22863048
TI  - Selenium supplementation for critical illness.

PMID- 22863050
TI  - Social media guidance, conflicts of interest, and health inequalities.

PMID- 22863051
TI  - The state of nursing and evidence-based practice.

PMID- 22863052
TI  - Health authorities' leadership reduces cholera deaths in Haiti.

PMID- 22863053
TI  - Gender inequality in awarded research grants.

PMID- 22863054
TI  - An unexpected trismus.

PMID- 22863057
TI  - Supplements in human islet culture: human serum albumin is inferior to fetal
      bovine serum.
AB  - Culture of human islets before clinical transplantation or distribution for
      research purposes is standard practice. At the time the Edmonton protocol was
      introduced, clinical islet manufacturing did not include culture, and human serum
      albumin (HSA), instead of fetal bovine serum (FBS),  was used during other steps
      of the process to avoid the introduction of xenogeneic material. When culture was
      subsequently introduced, HSA was also used for medium supplementation instead of
      FBS, which was typically used for research islet culture. The use of HSA as
      culture supplement was  not evaluated before this implementation. We performed a
      retrospective analysis of 103 high-purity islet preparations (76 research
      preparations, all with FBS culture supplementation, and 27 clinical preparations,
      all with HSA supplementation) for oxygen consumption rate per DNA content
      (OCR/DNA;  a measure of viability) and diabetes reversal rate in diabetic nude
      mice (a measure of potency). After 2-day culture, research preparations exhibited
      an average OCR/DNA 51% higher (p < 0.001) and an average diabetes reversal rate
      54% higher (p < 0.05) than clinical preparations,  despite 87% of the research
      islet preparations having been derived from research-grade pancreata that are
      considered of lower quality. In a prospective paired study on islets from eight
      research preparations, OCR/DNA was, on average, 27% higher with FBS
      supplementation than that with HSA supplementation  (p < 0.05). We conclude that
      the quality of clinical islet preparations can be improved when culture is
      performed in media supplemented with serum instead of albumin.

PMID- 22863058
TI  - Colestyramine slows gastric emptying of liquids and reduces appetite in healthy
      subjects.
AB  - BACKGROUND: There is evidence to suggest that the particulate resin
      colestyramine, a bile acid sequestrant formerly used as a cholesterol-lowering
      agent, enhances secretion of the gut hormone cholecystokinin (CCK). Established
      physiological actions of CCK include inhibition of gastric emptying and induction
      of satiation. This study evaluated the hypothesis that colestyramine, which is
      luminally retained, would slow gastric emptying of liquids and suppress appetite
      in humans. METHODS: Nine healthy volunteers consumed 500 mL liquid test meals
      containing 4 g colestyramine, 12 g colestyramine, or control (water alone), on
      three occasions, in a randomized order. The effect of colestyramine on gastric
      emptying was determined non-invasively using the (13) C-acetate breath test, and
      appetite and other gut-centered sensations were rated using visual analog scale
      questionnaires. KEY RESULTS: Colestyramine dose dependently slowed liquid gastric
      emptying compared with control (water) (4 g vs control, ~20% reduction, P < 0.05;
      12 g vs control, ~35% reduction, P < 0.01). Colestyramine also significantly
      reduced hunger (4 g vs control, ~20% reduction, P < 0.01), and the amount of food
      participants felt able to eat (12 g vs control, ~32% reduction, P < 0.001), but
      increased bloating (both doses, P < 0.05), with no effect on ratings of nausea.
      CONCLUSIONS & INFERENCES: This study provides the first evidence that
      colestyramine significantly slows liquid gastric emptying and reduces appetite in
      healthy humans. Colestyramine therefore presents an attractive gut-brain
      signaling research tool in that it is not absorbed and thus lacks potentially
      confounding postabsorptive effects. Furthermore, with clear effects on gastric
      emptying and appetite, colestyramine now merits consideration as a trial
      therapeutic strategy for appetite suppression and weight loss.

PMID- 22863056
TI  - Hepatitis C virus infection in the immunocompromised host: a complex scenario
      with variable clinical impact.
AB  - The relationship between Hepatitis C Virus (HCV) infection and immunosuppression
      is complex and multifaceted. Although HCV-related hepatocytolysis is classically
      interpreted as secondary to the attack by cytotoxic T lymphocytes against
      infected cells, the liver disease is usually exacerbated and more rapidly
      evolutive in immunosuppressed patients. This generally occurs during the
      immunosuppression state, and not at the reconstitution of the host response after
      immunosuppressive therapy discontinuation. The field of immunosuppression and HCV
      infection is complicated both by the different outcome observed in different
      situations and/or by contrasting data obtained in the same conditions, with
      several still unanswered questions, such as the opportunity to modify treatment
      schedules in the setting of post-transplant follow-up. The complexity of this
      field is further complicated by the intrinsic tendency of HCV infection in itself
      to lead to disorders of the immune system. This review will briefly outline the
      current knowledge about the pathogenesis of both hepatic and extrahepatic HCV
      related disorders and the principal available data concerning HCV infection in a
      condition of impairment of the immune system. Attention will be especially
      focused on some conditions - liver or kidney transplantation, the use of biologic
      drugs and cancer chemotherapy - for which more abundant and interesting data
      exist.

PMID- 22863059
TI  - Watershed-based riverine discharge loads and emission factor of perfluorinated
      surfactants in Korean peninsula.
AB  - Long-range transport of and exposure to perfluorinated substances (PFSs) strongly
      depend on their emission mode. In the present study, watershed-based riverine
      discharge loads and emission factors are estimated for perfluorooctanoate (PFOA),
      perfluorononanoate (PFNA), perfluorohexylsulfonate (PFHxS), and
      perfluorooctylsulfonate (PFOS) by using spatially distributed data of chemical
      concentrations together with water flows and a geographic information system
      (GIS). Average per capita emissions (emission factor, MUg capita(-1) d(-1)) are
      75 for PFOA, 36 for PFNA, 17 for PFHxS, and 43 for PFOS, which are several times
      lower than the estimates for Japan and the European continent. A relatively
      uniform distribution is observed for PFHxS and PFOS emission factors, while
      elevated values of PFOA and PFNA predominate in one of eight river basins. This
      may indicate the leading contribution of diffusive sources (e.g. nonpoint source)
      for PFHxS and PFOS versus the presence of localized point sources for PFOA and
      PFNA. The lower-upper bound of total riverine loads discharged annually from the
      Korean peninsula are in the range of 0.53-1.3 tons for PFOA, 0.09-0.60 tons for
      PFNA, 0.07-0.29 tons for PFHxS, and 0.19-0.73 tons for PFOS, accounting for <1%
      of global annual emissions. Furthermore, these riverine discharge loads are
      significantly greater than the discharge loads from a wastewater treatment plant,
      indicating the necessity of further study of nonpoint sources.

PMID- 22863060
TI  - The pH-dependence of organofluorine binding domain preference in dissolved humic
      acid.
AB  - In this study we explore the relationship between solution pH and the
      distribution of the binding interactions at different domains of a dissolved
      humic acid (HA) for three xenobiotics: pentafluoroaniline (PFA),
      pentafluorophenol (PFP), and hexafluorobenzene (HFB). The components of HA where
      xenobiotic interactions occur are identified using the (1)H{(19)F} Reverse
      Heteronuclear Saturation Transfer Difference (RHSTD) Nuclear Magnetic Resonance
      (NMR) spectroscopy experiment. At low pH, PFA and PFP interact preferentially
      with aromatic components of HA. Increasing pH reduces this preference.
      Conversely, HFB interacts with all components of HA equally, across the entire pH
      range. The possible roles of both aromatic-specific interactions and
      conformational changes of HA behind these observations are explored. It is shown
      that T-oriented pi-pi interactions at pi-electron accepting HA structures are
      slightly stronger for PFA and PFP than for HFB. Using DOSY NMR it is shown that
      the pH-dependence of the interactions is correlated with changes in the
      conformation of the carbohydrate components of HA rather than with the aromatic
      components. It is argued that the observed preference for aromatic HA is caused
      by restricted access to the non-aromatic components of HA at low pH. These HA
      components form tightly bound hydrophobic domains due to strong inter- and intra
      molecular hydrogen bonds. At high pH, these structures open up, making them more
      available for interactions with polar compounds.

PMID- 22863061
TI  - Polychlorinated biphenyls (PCBs) in marine fishes from China: levels,
      distribution and risk assessment.
AB  - Muscle tissues of large yellow croakers (Pseudosciaena crocea) and sliver pomfret
      (Pampus argenteus) from nine coastal cities of East China including Dalian,
      Tianjin, Qingdao, Shanghai, Zhoushan, Wenzhou, Fuzhou, Quanzhou and Xiamen were
      analyzed for polychlorinated biphenyl (PCB) concentrations. Thirty-six PCB
      congeners were quantified in the fishes, of which 11 congeners were dioxin-like
      PCBs. The total PCB concentrations of the present study were at the low end of
      the global range, which may be related to the smaller usage and shorter
      consumption history of PCBs in China. PCBs 18, 29, 52, 66, 101, 104, 138, 153,
      180 and 194 were the major constituents found in the fish samples. Regression
      analysis showed a strong positive correlation (R(2)=0.800; p<0.001) between total
      dioxin-like PCBs and total PCB concentrations, and that total PCB concentrations
      explain 80% of the variability in total dioxin-like PCB concentrations. Among the
      species investigated, significantly higher concentrations of total PCBs were
      found in croakers than in pomfrets, which may be attributed to their different
      feeding and living habits. No significant difference in total PCB concentrations
      among the cities was observed; principal component analysis (PCA) of PCB profiles
      indicated that PCB pollution came from similar sources in the sampling areas and
      that there may be other PCB sources in Dalian and Wenzhou. The calculated
      carcinogenic risks (CRs) from the two species based on a low consumption group
      and high consumption group were all greater than 10(-6), suggesting that daily
      exposure to dioxin-like PCBs via fish consumption results in a lifetime cancer
      risk of greater than one in one million. In contrast, the hazard quotients (HQs)
      of noncancer risks were all less than unity.

PMID- 22863062
TI  - Fish pollution with anthropogenic 137Cs in the southern Baltic Sea.
AB  - This paper presents the results of a study on changes in (137)Cs activity
      concentrations in three fish species from the southern Baltic Sea: cod (Gadus
      morhua), herring (Clupea harengus) and flounder (Platichtys flesus), in the
      period 2000-2010. During the study period a marked decline in cesium activity
      concentration in fish muscle tissue was observed, which reflected changes in
      radionuclide activity concentration in seawater. No statistically significant
      temporal trends were determined in changes of concentration factors
      (CF(fish/seawater)) calculated for the examined fish species. The analysis of
      (137)Cs activity as a function of ichthyological parameters revealed the lack of
      a relationship between radionuclide activity concentrations in herring muscle
      tissue and the fish age in an narrow age range (2-4 years). However, a reverse
      proportionality of total fish mass, as well as body length, against (137)Cs
      activity concentrations in muscles was well documented. The latter observation
      can be the direct result of the dilution effect related to the increase of fish
      body weight. (137)Cs activity concentration in muscle tissue of the five fish
      species forms a declining sequence: Gadus morhua, Platichthys flesus, Clupea
      harengus, Perca fluviatilis and Neogobius melanostomus.

PMID- 22863063
TI  - Enzymes and mediators hosted together in lipidic mesophases for the construction
      of biodevices.
AB  - Self-assembled, highly viscous, and optically transparent lipidic cubic phases
      are employed as matrices for enzyme-glucose dehydrogenase and vitamin K
      derivatives differing in hydrophobicity: phylloquinone (VitK(1)), menaquinone
      (VitK(2)), and menadione (VitK(3)). The lipidic cubic mesophase has been employed
      to hold these electroactive biological molecules in close vicinity of the
      electrode surface in order to study their behavior in the lipid environment by
      electrochemical methods. Liquid-crystalline properties of the analyzed samples of
      non-doped and doped phase were identified using X-ray and polarized microscopy.
      Incorporation of the enzyme together with the mediator in the lipidic matrix
      results in the formation of a catalytically active and stable film on the
      electrode surface and makes the modified electrode useful for the development of
      biosensors. Single-walled carbon nanotubes were employed to nanostructure the
      electrode surface in order to increase the working area of the electrode.

PMID- 22863064
TI  - Catalytic dechlorination of Aroclor 1242 by Ni/Fe bimetallic nanoparticles.
AB  - Ni/Fe bimetallic nanoparticles were synthesized for treatment of Aroclor 1242, in
      order to evaluate their applicability for in situ remediation of groundwater and
      soil contaminated by polychlorinated biphenyls (PCBs). Our experimental results
      indicate that the total PCB concentration changed during the reduction of 3,5
      dichlorobiphenyl (PCB 14), and biphenyl was produced as the final product.
      Initially, the concentration of 3-chlorobiphenyl (PCB 2) was increased in the
      prophase reaction and then slowly decreased, suggesting that Aroclor 1242 was
      first adsorbed by Ni/Fe nanoparticles, and then, the higher chlorinated congeners
      were converted gradually to the lower chlorinated congeners, and finally to
      biphenyl. The dechlorination efficiency of Aroclor 1242 reached approximately 80%
      at 25 degrees C in just 5h, then 95.6% and 95.8% in 10h and 24h, respectively.
      The study revealed that high Ni/Fe nanoparticle dosage and high Ni content in
      Ni/Fe nanoparticles favor the catalytic dechlorination reaction. Moreover, a
      comparison of different types of catalysts on the dechlorination of Aroclor 1242
      indicated that Ni/Mg and Mg powders showed a greater reactivity than Ni/Fe and Fe
      nanoparticles, respectively.

PMID- 22863065
TI  - Fabrication of quantum dots-encoded microbeads with a simple capillary fluidic
      device and their application for biomolecule detection.
AB  - Monodispersed quantum dots (QDs)-encoded polymer microbeads were generated using
      a simple capillary fluidic device (CFD). The polymer and QDs solution was
      emulsified into monodispersed microdroplets by the CFD and obtained droplets were
      solidified via solvent evaporation. Polymer microbeads can be fabricated in a
      range of different sizes through changing the flow rates of the two immiscible
      phases, and have a highly narrow size distribution and uniform shape. QDs
      encoding capacity of the microbeads was investigated through adjusting the
      concentrations and ratios of QDs in the polymer solution. Mono-color encoded
      microbeads with five intensities and a dual-color QDs-encoded 5*5 microbeads
      array were obtained, and the spectral profiles of the microbeads were examined by
      a fluorescent microscope coupled with a spectral imaging system. QDs-tagged
      microbeads prepared with this method were more stable than the porous beads
      swollen with QDs in the buffer with various pH and crosslinking chemicals.
      Finally, the application of such microbeads for biomolecule detection was
      demonstrated by conjugation of rabbit IgG molecules on the surface of the
      microbeads via carboxyl groups, which were then detected by fluorophores-labeled
      goat-anti-rabbit IgG antibodies.

PMID- 22863066
TI  - Identification and genotyping of human papillomavirus in a Spanish cohort of
      penile squamous cell carcinomas: correlation with pathologic subtypes, p16(INK4a)
      expression, and prognosis.
AB  - BACKGROUND: Penile squamous cell carcinoma (PSCC) is a tumor with a high
      metastatic potential. In PSCC the attributable fraction to human papillomavirus
      (HPV) is not well established. OBJECTIVE: We sought to provide novel data about
      the prevalence of HPV in a large series of penile intraepithelial neoplasia
      (PeIN) and invasive PSCC, correlating the results with the histologic subtype,
      p16(INK4a) immunostaining, and prognosis. METHODS: A total of 82 PSCC were
      included in the study, 69 invasive and 13 PeIN. HPV detection was performed by
      polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA
      enzyme immunoassay and genotyping with a reverse hybridization line probe assay.
      P16(INK4a) immunohistochemical expression on tissue microarrays was also
      analyzed. RESULTS: HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67
      invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV
      detection was significantly associated with some histologic subtypes: most
      basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15%
      of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent
      undifferentiated PeIN. Strong p16(INK4a) immunostaining correlated with hrHPV
      infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical
      overexpression. Both hrHPV-positive and p16(INK4a)-positive tumors showed a
      better overall survival without reaching statistical significance. LIMITATIONS:
      This was a retrospective study. CONCLUSIONS: Our results suggest that most hrHPV
      positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16(INK4a)
      immunostaining may be useful in identifying both etiologically related hrHPV
      positive tumors and those with better outcome. The routine use of p16(INK4a)
      staining should be incorporated in histologic evaluation of PSCC.

PMID- 22863068
TI  - Characterizing the transformation and transfer of nitrogen during the aerobic
      treatment of organic wastes and digestates.
AB  - The transformation and transfer of nitrogen during the aerobic treatment of seven
      wastes were studied in ventilated air-tight 10-L reactors at 35  degrees C.
      Studied wastes included distinct types of organic wastes and their digestates.
      Ammonia emissions varied depending on the kind of waste and treatment conditions.
      These emissions accounted for 2-43% of the initial nitrogen. Total nitrogen
      losses, which resulted mainly from ammonia emissions and nitrification
      denitrification, accounted for 1-76% of the initial nitrogen. Ammonification was
      the main process responsible for nitrogen losses. An equation which allows
      estimating the ammonification flow of each type of waste according to its
      biodegradable carbon and carbon/nitrogen ratio was proposed. As a consequence of
      the lower contribution of storage and leachate rates, stripping and nitrification
      rates of ammonia nitrogen were negatively correlated. This observation suggests
      the possibility of promotingnitrification in order to reduce ammonia emissions.

PMID- 22863067
TI  - High-throughput sequencing of small RNAs and analysis of differentially expressed
      microRNAs associated with pistil development in Japanese apricot.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of endogenous, small, non-coding RNAs
      that regulate gene expression by mediating gene silencing at transcriptional and
      post-transcriptional levels in high plants. However, the diversity of miRNAs and
      their roles in floral development in Japanese apricot (Prunus mume Sieb. et Zucc)
      remains largely unexplored. Imperfect flowers with pistil abortion seriously
      decrease production yields. To understand the role of miRNAs in pistil
      development, pistil development-related miRNAs were identified by Solexa
      sequencing in Japanese apricot. RESULTS: Solexa sequencing was used to identify
      and quantitatively profile small RNAs from perfect and imperfect flower buds of
      Japanese apricot. A total of 22,561,972 and 24,952,690 reads were sequenced from
      two small RNA libraries constructed from perfect and imperfect flower buds,
      respectively. Sixty-one known miRNAs, belonging to 24 families, were identified.
      Comparative profiling revealed that seven known miRNAs exhibited significant
      differential expression between perfect and imperfect flower buds. A total of 61
      potentially novel miRNAs/new members of known miRNA families were also identified
      by the presence of mature miRNAs and corresponding miRNA*s in the sRNA libraries.
      Comparative analysis showed that six potentially novel miRNAs were differentially
      expressed between perfect and imperfect flower buds. Target predictions of the 13
      differentially expressed miRNAs resulted in 212 target genes. Gene ontology (GO)
      annotation revealed that high-ranking miRNA target genes are those implicated in
      the developmental process, the regulation of transcription and response to
      stress. CONCLUSIONS: This study represents the first comparative identification
      of miRNAomes between perfect and imperfect Japanese apricot flowers. Seven known
      miRNAs and six potentially novel miRNAs associated with pistil development were
      identified, using high-throughput sequencing of small RNAs. The findings, both
      computationally and experimentally, provide valuable information for further
      functional characterisation of miRNAs associated with pistil development in
      plants.

PMID- 22863069
TI  - Quantifying uncertainty in LCA-modelling of waste management systems.
AB  - Uncertainty analysis in LCA studies has been subject to major progress over the
      last years. In the context of waste management, various methods have been
      implemented but a systematic method for uncertainty analysis of waste-LCA studies
      is lacking. The objective of this paper is (1) to present the sources of
      uncertainty specifically inherent to waste-LCA studies, (2) to select and apply
      several methods for uncertainty analysis and (3) to develop a general framework
      for quantitative uncertainty assessment of LCA of waste management systems. The
      suggested method is a sequence of four steps combining the selected methods:
      (Step 1) a sensitivity analysis evaluating the sensitivities of the results with
      respect to the input uncertainties, (Step 2) an uncertainty propagation providing
      appropriate tools for representing uncertainties and calculating the overall
      uncertainty of the model results, (Step 3) an uncertainty contribution analysis
      quantifying the contribution of each parameter uncertainty to the final
      uncertainty and (Step 4) as a new approach, a combined sensitivity analysis
      providing a visualisation of the shift in the ranking of different options due to
      variations of selected key parameters. This tiered approach optimises the
      resources available to LCA practitioners by only propagating the most influential
      uncertainties.

PMID- 22863070
TI  - Illegal hunting cases detected with molecular forensics in Brazil.
AB  - BACKGROUND: Illegal hunting is one of the major threats to vertebrate populations
      in tropical regions. This unsustainable practice has serious consequences not
      only for the target populations, but also for the dynamics and structure of
      tropical ecosystems. Generally, in cases of suspected illegal hunting, the only
      evidence available is pieces of meat, skin or bone. In these cases, species
      identification can only be reliably determined using molecular technologies.
      Here, we reported an investigative study of three cases of suspected wildlife
      poaching in which molecular biology techniques were employed to identify the
      hunted species from remains of meat. FINDINGS: By applying cytochrome b (cyt-b)
      and cytochrome oxidase subunit I (COI) molecular markers, the suspected illegal
      poaching was confirmed by the identification of three wild species, capybara
      (Hydrochoerus hydrochaeris), Chaco Chachalaca (Ortalis canicollis) and Pampas
      deer (Ozotoceros bezoarticus). In Brazil, hunting is a criminal offense, and
      based on this evidence, the defendants were found guilty and punished with fines;
      they may still be sentenced to prison for a period of 6 to 12 months.
      CONCLUSIONS: The genetic analysis used in this investigative study was suitable
      to diagnose the species killed and solve these criminal investigations. Molecular
      forensic techniques can therefore provide an important tool that enables local
      law enforcement agencies to apprehend illegal poachers.

PMID- 22863071
TI  - Molecular scaffold analysis of natural products databases in the public domain.
AB  - Natural products represent important sources of bioactive compounds in drug
      discovery efforts. In this work, we compiled five natural products databases
      available in the public domain and performed a comprehensive chemoinformatic
      analysis focused on the content and diversity of the scaffolds with an overview
      of the diversity based on molecular fingerprints. The natural products databases
      were compared with each other and with a set of molecules obtained from in-house
      combinatorial libraries, and with a general screening commercial library. It was
      found that publicly available natural products databases have different scaffold
      diversity. In contrast to the common concept that larger libraries have the
      largest scaffold diversity, the largest natural products collection analyzed in
      this work was not the most diverse. The general screening library showed,
      overall, the highest scaffold diversity. However, considering the most frequent
      scaffolds, the general reference library was the least diverse. In general,
      natural products databases in the public domain showed low molecule overlap. In
      addition to benzene and acyclic compounds, flavones, coumarins, and flavanones
      were identified as the most frequent molecular scaffolds across the different
      natural products collections. The results of this work have direct implications
      in the computational and experimental screening of natural product databases for
      drug discovery.

PMID- 22863072
TI  - Clinically significant bleeding in incurable cancer patients: effectiveness of
      hemostatic radiotherapy.
AB  - BACKGROUND: This study was performed to evaluate the outcome after hemostatic
      radiotherapy (RT) of significant bleeding in incurable cancer patients. METHODS:
      Patients treated by hemostatic RT between November 2006 and February 2010 were
      retrospectively analyzed. Bleeding was assessed according to the World Health
      Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 =
      clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding
      associated with fatality). The primary endpoint was bleeding at the end of RT.
      Key secondary endpoints included overall survival (OS) and acute toxicity. The
      bleeding score before and after RT were compared using the Wilcoxon signed rank
      test. Time to event endpoints were estimated using the Kaplan Meier method.
      RESULTS: Overall 62 patients were analyzed including 1 patient whose benign cause
      of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37-93) years.
      Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients,
      respectively. A median dose of 20 (range, 5-45) Gy of hemostatic RT was applied
      to the bleeding site. At the end of RT, there was a statistically significant
      difference in bleeding (p < 0.001); it was graded as 0 ( n = 39), 1 ( n = 12), 2
      ( n = 6), 3 ( n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3
      19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to
      bleeding. No grade 3 or above acute toxicity was observed. CONCLUSIONS:
      Hemostatic RT seems to be a safe and effective treatment for clinically and
      statistically significantly reducing bleeding in incurable cancer patients.

PMID- 22863073
TI  - Ultra high risk of psychosis on committal to a young offender prison: an
      unrecognised opportunity for early intervention.
AB  - BACKGROUND: The ultra high risk state for psychosis has not been studied in young
      offender populations. Prison populations have higher rates of psychiatric
      morbidity and substance use disorders. Due to the age profile of young offenders
      one would expect to find a high prevalence of individuals with pre-psychotic or
      ultra-high risk mental states for psychosis (UHR). Accordingly young offender
      institutions offer an opportunity for early interventions which could result in
      improved long term mental health, social and legal outcomes. In the course of
      establishing a mental health in-reach service into Ireland's only young offender
      prison, we sought to estimate unmet mental health needs. METHODS: Every third new
      committal to a young offenders prison was interviewed using the Comprehensive
      Assessment of At-Risk Mental States (CAARMS) to identify the Ultra High Risk
      (UHR) state and a structured interview for assessing drug and alcohol misuse
      according to DSM-IV-TR criteria, the Developmental Understanding of Drug Misuse
      and Dependence - Short Form (DUNDRUM-S). RESULTS: Over a twelve month period 171
      young male offenders aged 16 to 20 were assessed. Of these 39 (23%, 95%
      confidence interval 18% to 30%) met UHR criteria. UHR states peaked at 18 years,
      were associated with lower SOFAS scores for social and occupational function and
      were also associated with multiple substance misuse. The relationship with lower
      SOFAS scores persisted even when co-varying for multiple substance misuse.
      CONCLUSIONS: Although psychotic symptoms are common in community samples of
      children and adolescents, the prevalence of the UHR state in young offenders was
      higher than reported for community samples. The association with impaired
      function also suggests that this may be part of a developing disorder. Much more
      attention should be paid to the relationship of UHR states to substance misuse
      and to the health needs of young offenders.

PMID- 22863074
TI  - Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype
      catch-up program using United States claims data.
AB  - BACKGROUND: Analysis of US claims data from April 2010 to June 2011 estimated
      that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up
      eligible cohort would ever receive the catch-up vaccination; a previous analysis
      assumed 87%. METHODS: This updated figure was applied to a previously published
      10-year Markov model while holding all other inputs constant. RESULTS: Our model
      estimated that the catch-up program as currently implemented is estimated to
      prevent an additional 1.7 million cases of disease in children aged <= 59 months
      over a 10-year period, compared with routine PCV13 vaccination with no catch-up
      program. CONCLUSIONS: Because 39% catch-up uptake is less than the level of
      completion of the 4-dose primary PCV13 series, vaccine-preventable cases of
      pneumococcal disease and related deaths could be decreased further with
      additional uptake of catch-up vaccination in the catch-up eligible cohort.

PMID- 22863075
TI  - Defining retention and attrition in pre-antiretroviral HIV care: proposals based
      on experience in Africa.

PMID- 22863076
TI  - Linking alphaMSH with PPARgamma in B16-F10 melanoma.
AB  - We have discovered a new alpha-melanocyte stimulating hormone (alpha
      MSH)/peroxisome proliferator activated receptor-gamma (PPAR-gamma) connection in
      B16-F10 cells. Both PPAR-gamma up-regulation and its induction as an active
      transcription factor were observed in response to alpha-MSH. The alpha-MSH/PPAR
      gamma connection influenced both pigmentation and proliferation. The forskolin
      stimulated cAMP/PKA pathway was not able to induce either PPAR-gamma
      translocation into the nucleus or PPAR-gamma transcriptional activity. As the
      melanocortin-1 receptor, the specific receptor for the alpha-MSH, is a G-protein
      coupled receptor, we wondered whether the phosphatidylinositol [PI(4,5)P(2)
      /PLC(beta) ] signal pathway was involved in mediating the alpha-MSH-dependent
      PPAR-gamma activation. Employing inhibitors of PI(4,5)P(2) /PLC(beta)  pathway,
      the results of our experiments suggested that this pathway was promoted by alpha
      MSH and that alpha-MSH played a role in mediating PPAR-gamma activation. We have
      demonstrated, for the first time, that alpha-MSH induces the PI(4,5)P(2)
      /PLC(beta)  pathway, through analysis of the basic steps of the pathway. The
      alpha-MSH effect on PPAR-gamma was independent of animal species and was not
      correlated with the physio-pathological status.

PMID- 22863077
TI  - A new paradigm for teaching behavior change: implications for residency training
      in family medicine and psychiatry.
AB  - BACKGROUND: Primary care physicians (PCPs) provide ~50 % of all mental health
      services in the U.S. Given the widening gap between patient mental health needs
      and resources available to meet those needs, there is an increasing demand for
      family medicine and psychiatry trainees to master competencies in both behavioral
      medicine and primary care counseling during residency-if for no other reason than
      to accommodate the realities of medical practice given the oft present gap
      between the need for psychiatric services and the availability, quality, and/or
      affordability of specialized psychiatric care. To begin to address this gap, a
      skills-based, interactive curriculum based on motivational interviewing (MI) as a
      teaching method is presented. METHODS: The curriculum described in this paper is
      a four-week block rotation taught in the second year of residency. Motivational
      interviewing (MI) is used as a teaching approach toward the goal of clinical
      behavior change. Residents' strengths, personal choice and autonomy are
      emphasized. Each week of the rotation, there is a clinical topic and a set of
      specific skills for mastery. Residents are offered a "menu" of skills, role
      modeling, role/real play, practice with standardized patients (SP), and direct
      supervision in clinic. RESULTS: Thirty-nine residents have completed the
      curriculum. Based on residents' subjective reporting using pre-post scales (i.e.,
      importance and confidence), all participants to date have reported substantial
      increases in confidence/self-efficacy using primary care counseling skills in
      their continuity clinic. CONCLUSIONS: This paper presents an innovative,
      empirically based model for teaching the essential skills necessary for
      physicians providing care for patients with mental/emotional health needs as well
      as health-behavior change concerns. Implications for training in the broader
      context, particularly as it relates to multi-disciplinary and collaborative
      models of teaching/training are discussed.

PMID- 22863078
TI  - High pressure treatments on the inactivation of Salmonella Enteritidis and the
      characteristics of beef carpaccio.
AB  - The effect of high pressure (HP) on Salmonella enterica subsp. enterica serovar
      Enteritidis in beef carpaccio stored under temperature abuse conditions (8 
      degrees C) during 30 days was investigated. After treatment, reductions of S.
      Enteritidis were 3.68 and 5.94 log cfu/g in samples pressurized at 450 MPa for 5
      and 10 min, respectively, whereas the pathogen was only detected after enrichment
      of samples treated at 450 MPa for 15 min. During storage, counts of S.
      Enteritidis decreased 0.26 log cfu/g in non-pressurized carpaccio, 1.33 log cfu/g
      in carpaccio treated at 450 MPa for 5 min and were only detected after enrichment
      in carpaccio pressurized at 450 MPa for 10 or 15 min. Color (L*, a* and b*)
      varied with pressurization and storage, with higher changes in carpaccio treated
      at longer pressurization times. Shear resistance was slightly lower in treated
      samples just after pressurization, but increased at the end of the storage
      period. Maximum force was less affected by treatment.

PMID- 22863079
TI  - Inspection of lymph nodes for caseous lymphadenitis and its effect on the density
      of microbes on sheep carcasses.
AB  - This study aimed to measure the amount of microbial contamination caused by
      inspecting the lymph nodes of adult sheep carcasses for caseous lymphadenitis
      (CLA). Surface swabs from carcasses pre-inspection (N=296) and post-inspection
      (N=296) were obtained for enumeration of indicator organisms at three commercial
      abattoirs. At the scapular site, inspection doubled the probability of detecting
      E. coli (Pr before=0.35, Pr after=0.67) and increased the expected count of E.
      coli from 2 cfu/cm2 to 13 cfu/cm2. Inspection at the rump site increased the
      probability of detecting E. coli by 1.1 times (Pr before=0.84, Pr after=0.93) and
      increased the expected count from 32 cfu/cm2 to 45 cfu/cm2. Effects were also
      observed for Enterobacteriaceae and total viable count. The findings show that
      routine inspection of adult sheep carcasses for CLA has a detrimental impact on
      carcass microbiological traits.

PMID- 22863080
TI  - alpha-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats.
AB  - BACKGROUND: Insulin resistance, oxidative stress, inflammation and innate immune
      system activation contribute to the development of non-alcoholic fatty liver
      disease (NAFLD) through steatosis and inflammation in the liver. The powerful
      antioxidant alpha-lipoic acid (ALA) has been shown to improve insulin sensitivity
      and suppress inflammatory responses. This study explores how ALA administration
      protects against NAFLD. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats
      were divided into two groups (treated with 200 mg/kg/day of ALA or untreated) at
      12 weeks of age and sacrificed at 28 weeks of age. RESULTS: Serum levels of
      insulin, free fatty acids, total cholesterol, triglyceride, leptin, IL-6 and
      blood glucose were decreased in ALA-treated rats. Serum adiponectin levels were
      higher in ALA-treated rats. ALA treatment decreased the expression of sterol
      regulatory element binding protein-1 and acetyl CoA carboxylase, and increased
      glucose transporter-4 expression in the livers of OLETF rats. Expression of the
      antioxidant enzymes heme oxygenase-1 and Cu/Zn-superoxide dismutase was increased
      in the livers of ALA-treated rats. The lipid peroxidation marker 4-hydroxynonenal
      was decreased in the liver of ALA-treated rats. Proteins associated with innate
      immune activation (Toll-like receptor-4 and high-mobility group protein box-1)
      and inflammatory markers (vascular cell adhesion molecule-1, intercellular
      adhesion molecule-1, and cyclooxygenase-2) were decreased in the livers of ALA
      treated rats. CONCLUSIONS: Chronic ALA supplementation prevents NAFLD through
      multiple mechanisms by reducing steatosis, oxidative stress, immune activation
      and inflammation in the liver.

PMID- 22863081
TI  - Preputial/penile skin flap, as a dorsal onlay or tubularized flap: a versatile
      substitute for complex anterior urethral stricture.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? For long complex anterior urethral
      stricture augmentation urethroplasty is considered the standard procedure but the
      best substitute material is still to be ascertained. Preputial/penile skin is a
      very good substitute especially when used as a dorsal onlay. It demonstrates
      exceptional functional and cosmetic results even in patients with unsuitable oral
      mucosa. OBJECTIVE: * To present our experience of single-stage reconstruction of
      urethral stricture with preputial/penile skin flap, as a dorsal onlay flap (DOF)
      where there is an adequate urethral plate and as a tubularized flap (TF) where
      there is a compromised urethral plate, in cases of complex anterior urethral
      strictures. MATERIALS AND METHODS: * We retrospectively reviewed 144 patients,
      who underwent single-stage repair of pendular /bulbar urethral strictures with
      preputial/penile flap as either a DOF or a TF, between January 2001 and December
      2008. * Patients were divided into three groups: Group 1 consisted of patients
      who underwent transverse preputial DOF; Group 2 consisted of those who underwent
      tube urethroplasty; and Group 3 consisted of those patients who were circumcised
      and for whom the penile skin was used as a DOF (circumpenile flap). * Patients
      were followed up by physical examination, retrograde urethrography, uroflowmetry
      and post-void residual urine measurement. RESULTS: * The mean follow-up was 40.1
      months (range 36-84 months). * The primary success rates at 1 year follow-up were
      90, 85 and 93.3% for Groups1, 2 and 3, respectively, and at 3-years follow-up
      they were 85, 75 and 86.7%, respectively. * Half of the recurrences were
      successfully managed with a single visual internal urethrotomy or dilatation. *
      The secondary success rate was defined as recurrent stricture managed by a single
      endoscopic procedure and was 5, 10 and 6.8% in Groups 1, 2 and 3, respectively.
      The overall success rate was 90.85 and 93.3%, respectively. * A total of 75% of
      the patients in the study completed 60 months of follow-up with no additional
      recurrence. CONCLUSIONS: * A preputial/penile flap for complex anterior urethral
      stricture is a good treatment option, with results similar to other techniques,
      has acceptable donor site morbidity and is effective even in circumcised patients
      and for those patients with unsuitable oral mucosa. * A DOF is less likely to
      lead to diverticula formation and post-void dribbling. TFs have a higher failure
      rate than DOFs but, when combined judiciously with secondary endoscopic
      procedures, can provide good results.

PMID- 22863082
TI  - A symposium and workshop report from the Global Nutrition and Epidemiologic
      Transition Initiative: nutrition transition and the global burden of type 2
      diabetes.
AB  - The present report summarises the symposium 'Nutrition Transition and the Global
      Burden of Type 2 Diabetes' and a workshop on strategies for dietary interventions
      to prevent type 2 diabetes held by the Global Nutrition and Epidemiologic
      Transition Initiative, Boston, MA, USA in November 2011. The objectives of this
      event were to bring attention to the global epidemic of type 2 diabetes in light
      of the ongoing nutrition transition worldwide, especially in low- and middle
      income countries, and to highlight the present evidence on key dietary risk
      factors contributing to the global diabetes burden. The meeting put forward ideas
      for further research on this topic and discussed practical recommendations to
      design and implement culturally appropriate dietary interventions with a focus on
      improving carbohydrate quality to help alleviate this growing health problem.

PMID- 22863083
TI  - Optimizing the swallow protocol of clinical high-resolution esophageal manometry
      studies.
AB  - BACKGROUND: The Chicago Classification (CC) of Esophageal Motility Disorders is
      based on 10 water swallows performed in the supine position. The aim of the study
      was to assess whether upright and provocative swallows (PS) provided important
      information beyond that obtained from the standard supine manometric protocol.
      METHODS: Two independent investigators reviewed high-resolution manometry (HRM)
      studies of 148 patients with both supine and upright liquid swallows and
      additional studies from patients with PS (increased volume, viscosity, and a
      marshmallow) for a resultant change in CC diagnoses. Significant diagnostic
      changes were defined as a change from normal or borderline motor function to
      abnormal motor function, esophagogastric junction (EGJ) outflow obstruction, or
      achalasia. Discordant diagnoses were reviewed and the Kappa test was used to
      evaluate the agreement between diagnoses in the different protocols. KEY RESULTS:
      The overall agreement in diagnosis between the five supine swallows and the five
      upright swallows was good (k = 0.583). Changing to the upright position elicited
      a significant diagnostic change in 10.1% (15/148) of cases. The PS suggested an
      alternative diagnosis from the supine position in 14 of 75 studies (18.7%); 11 of
      these changed to EGJ obstruction during viscous or solid bolus challenges.
      CONCLUSIONS & INFERENCES: Changing position in HRM elicited a significant change
      in diagnosis in about 10% of studies, whereas provocative bolus challenges with
      viscous liquid and marshmallows increased the detection of EGJ outflow
      obstruction. Performing manometric evaluations in both positions with PS may
      increase the yield of standard HRM technique.

PMID- 22863084
TI  - Priorities in the prevention and control of multidrug-resistant
      Enterobacteriaceae in hospitals.
AB  - BACKGROUND: Multidrug-resistant Enterobacteriaceae (MDE) are a major public
      health threat due to international spread and few options for treatment.
      Furthermore, unlike meticillin-resistant Staphylococcus aureus (MRSA), MDE
      encompass several genera and multiple resistance mechanisms, including extended
      spectrum beta-lactamases and carbapenemases, which complicate detection in the
      routine diagnostic laboratory. Current measures to contain spread in many
      hospitals are somewhat ad hoc as there are no formal national or international
      guidelines. AIM: We sought to establish what should be the priorities for the
      prevention and control of MDE and what is feasible for implementation. We also
      identify areas for further research. METHODS: We reviewed the published
      literature and other sources e.g. national agencies, for measures and
      interventions used to control MDE. FINDINGS: Certain categories of at risk
      patients should be screened, especially in critical care areas, using appropriate
      laboratory methods. Standard and contact precautions are essential and hand
      hygiene compliance requires continued emphasis and high compliance levels. As MDE
      may persist on environmental surfaces for weeks, environmental decontamination
      could also be an effective control intervention. There are limited options for
      decolonisation with inadequate studies to date and antibiotic stewardship within
      and outside the hospital remains important. CONCLUSION: As there is a clear
      deficit in the evidence base to infor guidance on prevention and control,
      research in key areas, such as rapid detection, is urgently required.

PMID- 22863085
TI  - Sputter-prepared (001) BiFeO3 thin films with ferromagnetic L10-FePt(001)
      electrode on glass substrates.
AB  - Highly textured BiFeO3(001) films were formed on L10-FePt(001) bottom electrodes
      on glass substrates by sputtering at reduced temperature of 400 degrees C. Good
      electric polarization 2Pr = 80 and 95 MUC/cm2, comparable to that of the reported
      epitaxial films, and coercivity Ec = 415 and 435 kV/cm are achieved in the
      samples with 20-nm- and 30-nm-thick electrodes. The BiFeO3(001) films show
      different degrees of compressive strain. The relation between the variations of
      strain and 2Pr suggests that the enhancement of 2Pr resulted from the strain
      induced rotation of spontaneous polarization. The presented results open
      possibilities for the applications based on electric-magnetic interactions.

PMID- 22863086
TI  - Role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine
      (C-X-C motif) receptor 6 expression in gastric carcinomas.
AB  - The chemokine ligand CXC chemokine ligand 16 and its receptor chemokine (C-X-C
      motif) receptor 6 are up-regulated in many types of cancer and give rise to more
      aggressive behavior by regulating proliferation and angiogenesis. To clarify the
      role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine
      (C-X-C motif) receptor 6 expression in gastric carcinoma, their expression was
      examined by immunohistochemistry of tissue microarrays containing gastric
      carcinoma and nonneoplastic mucosa, reverse transcription-polymerase chain
      reaction, and Western blotting and by enzyme-linked immunosorbent assay to
      determine the CXC chemokine ligand 16 concentration in serum. Expression was
      compared with the clinicopathologic features of the carcinomas. All carcinoma and
      epithelial cells showed CXC chemokine ligand 16 and chemokine (C-X-C motif)
      receptor 6 messenger RNA expression to various degrees. Among 28 pairs of gastric
      carcinoma and normal tissues, there was higher CXC chemokine ligand 16 expression
      in carcinoma than in adjacent mucosa (P < .05), whereas the converse was true for
      chemokine (C-X-C motif) receptor 6 (P < .05). Nuclear CXC chemokine ligand 16
      expression correlated inversely with the depth of invasion, lymphatic invasion,
      Union Internationale Contre le Cancer stage, and favorable prognosis. The serum
      CXC chemokine ligand 16 concentration was lower in male patients or patients 55
      years or older than in female or younger patients, respectively (P < .05).
      Patients with lymphatic invasion or mixed-type carcinoma showed lower CXC
      chemokine ligand 16 concentrations than those with no lymphatic invasion or with
      diffuse-type carcinoma (P < .05). Aberrant expression of CXC chemokine ligand 16
      and chemokine (C-X-C motif) receptor 6 might be involved in gastric
      carcinogenesis. The expression and serum concentration of CXC chemokine ligand 16
      could indicate the aggressiveness and prognosis of gastric carcinomas.

PMID- 22863087
TI  - Coexpression of B-lymphoma Moloney murine leukemia virus insertion region-1 and
      sex-determining region of Y chromosome-related high mobility group box-2 in
      cervical carcinogenesis.
AB  - B-lymphoma Moloney murine leukemia virus insertion region-1 is an oncogene in
      various human tumors, and overexpression correlates with a poor clinical outcome.
      Sex-determining region of Y chromosome-related high mobility group box-2, coding
      for a critical transcription factor determining the fate of stem cells, was
      recently identified as an oncogene in human cervical carcinoma and other tumors.
      However, the roles of B-lymphoma Moloney murine leukemia virus insertion region-1
      and sex-determining region of Y chromosome-related high mobility group box-2 in
      the pathogenesis of cervical carcinoma are poorly understood. We initially
      observed a more pronounced increase in B-lymphoma Moloney murine leukemia virus
      insertion region-1 protein expression in primary cervical carcinoma than in
      normal cervical tissues, and B-lymphoma Moloney murine leukemia virus insertion
      region-1 protein expression correlated significantly with sex-determining region
      of Y chromosome-related high mobility group box-2 protein expression, as seen by
      Western blotting (r = 0.75; P < .01). Furthermore, B-lymphoma Moloney murine
      leukemia virus insertion region-1 and sex-determining region of Y chromosome
      related high mobility group box-2 both had higher expression in cervical
      carcinoma than in normal cervical tissue, and the amounts correlated with
      pathologic grade. Immunofluorescence analysis showed that B-lymphoma Moloney
      murine leukemia virus insertion region-1 colocalized in the nucleus with sex
      determining region of Y chromosome-related high mobility group box-2 in both
      normal cervical tissue and cervical carcinoma. From the cervical carcinoma cell
      line SiHa, we isolated 2 clones, B-lymphoma Moloney murine leukemia virus
      insertion region-1(+)/sex-determining region of Y chromosome-related high
      mobility group box-2(+) (SiHa-3) and B-lymphoma Moloney murine leukemia virus
      insertion region-1(-)/sex-determining region of Y chromosome-related high
      mobility group box-2(-) (SiHa-2). The SiHa-3 cells grew better in vitro and
      formed tumors more readily in vivo than did SiHa-2. Knockout of sex-determining
      region of Y chromosome-related high mobility group box-2 inhibited cell growth in
      vitro with a block at G1/S. In contrast, knockout of B-lymphoma Moloney murine
      leukemia virus insertion region-1 did not affect either cell growth in vitro or
      the cell cycle. Interference with either B-lymphoma Moloney murine leukemia virus
      insertion region-1 or sex-determining region of Y chromosome-related high
      mobility group box-2 in SiHa-3 significantly inhibited tumorigenesis (P < .05).
      Coexpression of B-lymphoma Moloney murine leukemia virus insertion region-1 and
      sex-determining region of Y chromosome-related high mobility group box-2 may
      promote cervical carcinogenesis.

PMID- 22863088
TI  - Comparison of cardiomyogenic potential among human ESC and iPSC lines.
AB  - We recently reported that, following induction of clumps of pluripotent H1 human
      embryonic stem cells (hESCs) with activin-A and Bmp4 in defined medium for 5
      days, widespread differentiation of rhythmically contracting cardiomyocytes
      occurs within 3-4 weeks. In this study, the same approach was used to assess
      whether human induced pluripotent stem cells (hiPSCs), which may theoretically
      provide an unlimited source of patient-matched cells for transplantation therapy,
      can similarly undergo cardiomyocyte differentiation. Differentiation of four
      pluripotent cell lines (H1 and H9 hESCs and C2a and C6a hiPSCs) was compared in
      parallel by monitoring rhythmic contraction, morphologic differentiation, and
      expression of cardiomyogenic genes. Based on expression of the cardiomyogenic
      lineage markers MESP1, ISL1, and NKX2-5, all four cell lines were induced into
      the cardiomyogenic lineage. However, in contrast to the widespread appearance of
      striations and rhythmic contractility seen in H9 and especially in H1 hESCs, both
      hiPSC lines exhibited poor terminal differentiation. These findings suggest that
      refined modes of generating hiPSCs, as well as of inducing cardiomyogenesis in
      them, may be required to fulfill their potential as agents of cardiac
      regeneration.

PMID- 22863089
TI  - Association between stall surface and some animal welfare measurements in
      freestall dairy herds using recycled manure solids for bedding.
AB  - The objective of this cross-sectional study was to investigate the association
      between stall surface and some animal welfare measurements in upper Midwest US
      dairy operations using recycled manure solids as bedding material. The study
      included 34 dairy operations with herd sizes ranging from 130 to 3,700 lactating
      cows. Forty-five percent of the herds had mattresses and 55% had deep-bedded
      stalls. Farms were visited once between July and October 2009. At the time of
      visit, at least 50% of the cows in each lactating pen were scored for locomotion,
      hygiene, and hock lesions. On-farm herd records were collected for the entire
      year and used to investigate mortality, culling, milk production, and mastitis
      incidence. Stall surface was associated with lameness and hock lesion prevalence.
      Lameness prevalence (locomotion score >= 3 on a 1 to 5 scale) was lower in deep
      bedded freestalls (14.4%) than freestalls with mattresses (19.8%). Severe
      lameness prevalence (locomotion score >= 4) was also lower for cows housed in
      deep-bedded freestalls (3.6%) than for cows housed in freestalls with mattresses
      (5.9%). In addition, the prevalence of hock lesions (hock lesion scores >= 2 on a
      1 to 3 scale, with 1=no lesion, 2=hair loss or mild lesion, and 3=swelling or
      severe lesion) and severe hock lesions (hock lesion score=3) was lower in herds
      with deep-bedded freestalls (49.4%; 6.4%) than in herds with mattresses (67.3%;
      13.2%). Herd turnover rates were not associated with stall surface; however, the
      percentage of removals due to voluntary (low milk production, disposition, and
      dairy) and involuntary (death, illness, injury, and reproductive) reasons was
      different between deep-bedded and mattress-based freestalls. Voluntary removals
      averaged 16% of all herd removals in deep-bedded herds, whereas in mattress
      herds, these removals were 8%. Other welfare measurements such as cow hygiene,
      mortality rate, mastitis incidence, and milk production were not associated with
      stall surface.

PMID- 22863090
TI  - Soybean meal substitution with a yeast-derived microbial protein source in dairy
      cow diets.
AB  - The objective of this study was to examine the effects substituting soybean meal
      with a yeast-derived microbial protein (YMP) on rumen and blood metabolites, dry
      matter intake, and milk production of high-producing dairy cows. Sixteen Holstein
      cows (12 multiparous and 4 primiparous), 93 +/- 37 DIM (mean +/- SD) at the
      beginning of the experiment, were used in a 4*4 Latin square design with four 28
      d periods. Cows were blocked by parity and production, with 1 square consisting
      of 4 animals fitted with rumen cannulas. Basal diets, formulated for 16.1% crude
      protein and 1.56 Mcal/kg of net energy for lactation, contained 40% corn silage,
      20% alfalfa hay, and 40% concentrate mix. During each period, cows were fed 1 of
      4 treatment diets corresponding to YMP (DEMP; Alltech Inc., Nicholasville, KY)
      concentrations of 0, 1.14, 2.28, and 3.41% DM. Soybean meal (44% CP) was replaced
      by YMP to attain isonitrogenous and isoenergetic diets. Dietary treatments had no
      effect on pH and on most ruminal volatile fatty acid concentrations, with the
      exception of isovalerate, which decreased linearly with the addition of YMP.
      Rumen ammonia concentration decreased linearly, whereas free amino acids, total
      amino acid nitrogen, and soluble proteins weighing more than 10 kDa showed a
      cubic response on rumen N fractionation. A quadratic response was observed in
      oligopeptides that weighed between 3 and 10 kDa and peptides under 3kDa when
      expressed as percentages of total amino acids and total nitrogen. Although
      nonesterified fatty acid concentration in blood did not differ between
      treatments, beta-hydroxybutyrate and plasma glucose increased linearly as YMP
      increased. Dry matter intake showed a cubic effect, where cows fed 1.14, and
      3.41% YMP had the highest intake. Milk production was not affected by YMP,
      whereas a trend was observed for a quadratic increase for 4% fat-corrected milk
      and energy-corrected milk. Medium- and long-chain fatty acid concentrations in
      milk increased quadratically, which elicited similar effects on milk fat
      concentration and yield. Total solids percentage and yield, and milk urea
      nitrogen also showed quadratic effects as YMP increased in the diet. No effects
      were observed on feed efficiency, milk protein, and lactose percentage or yield.
      A complementary in vitro study demonstrated a quadratic tendency for apparent and
      true dry matter digestibility as YMP was added to the diet. It was concluded that
      the substitution of soybean meal with YMP increased the percentage of total
      solids in milk and tended to improve energy-corrected and fat-corrected milk
      production in high-producing dairy cows consuming high-forage diets.

PMID- 22863091
TI  - Improved accuracy of genomic prediction for dry matter intake of dairy cattle
      from combined European and Australian data sets.
AB  - With the aim of increasing the accuracy of genomic estimated breeding values for
      dry matter intake (DMI) in dairy cattle, data from Australia (AU), the United
      Kingdom (UK), and the Netherlands (NL) were combined using both single-trait and
      multi-trait models. In total, DMI records were available on 1,801 animals,
      including 843 AU growing heifers with records on DMI measured over 60 to 70 d at
      approximately 200 d of age, and 359 UK and 599 NL lactating heifers with records
      on DMI during the first 100 d in milk. The genotypes used in this study were
      obtained from the Illumina Bovine 50K chip (Illumina Inc., San Diego, CA). The
      AU, UK, and NL genomic data were matched using the single nucleotide polymorphism
      (SNP) name. Quality controls were applied by carefully comparing the genotypes of
      40 bulls that were available in each data set. This resulted in 30,949 SNP being
      used in the analyses. Genomic predictions were estimated with genomic REML, using
      ASReml software. The accuracy of genomic prediction was evaluated in 11
      validation sets; that is, at least 3 validation sets per country were defined.
      The reference set (in which animals had both DMI phenotypes and genotypes) was
      either AU or Europe (UK and NL) or a multi-country reference set consisting of
      all data except the validation set. When DMI for each country was treated as the
      same trait, use of a multi-country reference set increased the accuracy of
      genomic prediction for DMI in UK, but not in AU and NL. Extending the model to a
      bivariate (AU-EU) or trivariate (AU-UK-NL) model increased the accuracy of
      genomic prediction for DMI in all countries. The highest accuracies were
      estimated for all countries when data were analyzed with a trivariate model, with
      increases of up to 5.5% compared with univariate models within countries.

PMID- 22863092
TI  - Necropsy as a means to gain additional information about causes of dairy cow
      deaths.
AB  - High mortality among dairy cows constitutes a problem both financially and in
      relation to animal welfare. Knowledge about causes of death is a fundamental step
      toward reducing cow mortality. Several studies have evaluated causes of dairy cow
      deaths. However, the vast majority of studies describing causes of death are
      based on questionnaires with farmers or veterinarians. It is uncertain to what
      degree such information is sufficient and reflects the true cause of death or
      euthanasia. In this study, proximate causes of death were evaluated based on a
      thorough necropsy of a random sample of 79 Danish dairy cows at an incineration
      plant. The necropsy was combined with information about the farmer's perception
      regarding the cause of death and information about disease treatments from the
      Danish Cattle Database. Pneumonia and locomotor disorders were found to be the
      most predominant proximate causes of death. Often the death occurred after a
      prolonged period during which the cow suffered several different disorders, even
      though this was often not noticed by the farmer. Causes of death stated by the
      farmers agreed with the necropsy results in 50 to 64% of cases. Information about
      disease treatments from the Danish Cattle Database agreed with the necropsy
      results in 34 to 39% of cases. All 3 sources of information about cause of death
      agreed in only 1 out of 4 cases, and even when the farmer and the disease
      recordings did agree with the necropsy results, the latter often gave additional
      information about the cause of death. In many situations, therefore, a necropsy
      may be a valuable tool when trying to control excessive cow mortality in a herd.

PMID- 22863093
TI  - Effects of lactation and pregnancy on metabolic and hormonal responses and
      expression of selected conceptus and endometrial genes of Holstein dairy cattle.
AB  - Objectives were to characterize postpartum metabolic and hormonal differences
      between nonlactating and lactating dairy cows, evaluate lactation and pregnancy
      effects on endometrium and conceptus expression of selected genes, and
      characterize associations between conceptus and endometrial expression of genes
      in early pregnancy (d 17). Pregnant heifers were assigned randomly after calving
      to a lactating group (L, n=17) and a nonlactating group (NL, n=16). The L cows
      were fed a total mixed ration [1.65 Mcal of net energy for lactation (NE(L))/kg,
      16.5% crude protein (CP)] ad libitum, and the NL cows were fed a maintenance
      ration (1.45 Mcal of NE(L)/kg, 12.2% CP) once per day. All cows were
      presynchronized and enrolled in a timed artificial insemination (TAI) protocol;
      10 cows in the L and 12 in the NL received TAI. On d 17 after GnRH and TAI, cows
      were slaughtered and endometrial and conceptus tissues collected. The Affymetrix
      Bovine Genome DNA Microarray (Affymetrix Inc., Santa Clara, CA) was used to
      assess conceptus and endometrial gene expression. The L cows had higher body
      temperature than the NL cows (38.4 vs. 38.2 degrees C), and the NL cows cycled
      earlier than the L cows (26.3 vs. 34.7 d in milk). Cows in the L group had
      greater plasma concentrations of beta-hydroxybutyrate (4.90 vs. 2.97 mg/dL) and
      blood urea N (11.6 vs. 6.5mg/dL) and lower concentrations of glucose (74.0 vs.
      79.9 mg/dL) compared with NL cows. Insulin-like growth factor-1 was lower for L
      compared with NL (140.5 vs. 198.2 ng/mL) and was greater for cows subsequently
      classified pregnant compared with cyclic (191.0 vs. 147.6 ng/mL). The
      concentration of progesterone from GnRH or TAI (d 0) until d 17 was lower for L
      cows than for NL cows. Gene expression analyses indicated that all conceptuses
      (n=13) expressed pregnancy-associated glycoprotein (PAG) genes PAG2, PAG8, PAG11,
      and PAG12. The same PAG family genes were observed in the endometrium of some
      pregnant cows. Simple and standard partial correlation analyses detected
      associations of conceptus PAG11 with prostaglandin regulatory genes. In
      conclusion, lactation altered metabolic status, delayed initiation of cyclicity,
      and decreased concentrations of progesterone in pregnant cows. Early expression
      of PAG genes in the conceptus may contribute to successful development of early
      pregnancy and possibly alter mechanisms related with embryo survival such as
      prostaglandin synthesis.

PMID- 22863094
TI  - Herd-level association of serum metabolites in the transition period with
      disease, milk production, and early lactation reproductive performance.
AB  - The objective was to identify herd-level indicators expressed as a proportion of
      sampled animals with increased nonesterified fatty acids (NEFA) or beta
      hydroxybutyric acid (BHBA), or decreased calcium in wk -1 and wk +1 relative to
      calving that were associated with herd-level incidence of retained placenta,
      metritis and displaced abomasum, milk production, and probability of pregnancy at
      the first artificial insemination (AI). Fifty-five Holstein freestall dairy herds
      in the United States and Canada were visited weekly. Blood was collected from
      2,365 cows around parturition, and serum concentrations of NEFA, BHBA, and
      calcium were determined. Different cow-level metabolite thresholds associated
      with detrimental health or productivity in previous studies were used to classify
      animals into high- and low-risk metabolite concentration groups. For wk -1 and wk
      +1 relative to calving, a herd-level threshold was determined as the proportion
      of sampled animals in the high-risk metabolite concentration groups with the
      strongest association with increased incidence of disease, milk loss, or
      decreased pregnancy at the first AI. The odds of displaced abomasum after calving
      were higher in herds that had >= 25% of the animals with BHBA >= 1,400 MUmol/L in
      wk +1 [odds ratio (OR)=2.1; 95% confidence interval (CI)=1.0-4.2)] or >= 35% of
      the animals with calcium <= 2.1 mmol/L in wk +1 (OR=2.4; CI=1.3-4.3). Herd-level
      thresholds of >=15% of the cows with BHBA >= 800 MUmol/L in wk -1 and >= 15% of
      the cows with calcium <=2.1mmol/L in wk +1 were associated with milk loss (+/-SE)
      of 4.4+/-1.7 and 3.8 +/- 1.4 kg/d per cow, respectively. When only multiparous
      cows were considered, herds with >=30% of the multiparous cows with NEFA >=0.5
      mEq/L in wk -1 were associated with a 3.0 +/- 1.5 kg/d per cow milk loss. The
      odds of pregnancy at first AI were lower in herds that had >= 5% of the cows with
      calcium <= 2.1 mmol/L in wk -1 (OR=0.7; CI=0.5-1.0), or >= 30% of the cows with
      NEFA >= 1.0 mEq/L (OR=0.6; CI=0.4-0.9) or >= 25% of the cows with calcium <=2.1
      mmol/L in wk +1 (OR=0.7; CI=0.5-0.9). When only multiparous cows were considered,
      the odds of pregnancy at first AI were lower in herds that had >=50% of
      multiparous cows with NEFA >=0.5 mEq/L in wk -1 (OR=0.5; CI=0.2-0.9). In
      conclusion, several herd-level thresholds for the proportion of cows with
      increased NEFA or BHBA, or decreased calcium in the week before and after calving
      were associated with higher risk of displaced abomasum, milk loss at the first
      Dairy Herd Improvement Association test, and decreased pregnancy at first AI. The
      association found between precalving BHBA and milk production is promising due to
      the availability of several cow-side tests for measuring BHBA. Some of the herd
      level associations differed from the previously described cow-level associations,
      suggesting the potential of interpreting periparturient metabolic challenges at
      the herd level, where changes in diet and management are generally implemented.

PMID- 22863095
TI  - The relationship between rumen acidosis resistance and expression of genes
      involved in regulation of intracellular pH and butyrate metabolism of ruminal
      epithelial cells in steers.
AB  - Past research has focused on the prevention and management of subacute rumen
      acidosis by manipulating the ration; however, the severity of acidosis varies
      even among animals fed a common high-grain diet. The objectives of this study
      were to compare the ruminal volatile fatty acid (VFA) profile and expression of
      genes involved in the metabolism of butyrate, the VFA most extensively
      metabolized by the ruminal epithelium, and intracellular pH regulation in ruminal
      epithelial cells between acidosis-resistant (AR) and acidosis-susceptible (AS)
      steers. Acidosis indexes (area per day under pH 5.8 divided by dry matter intake)
      were measured for 17 steers fed a common high-grain diet, and the 3 steers with
      the lowest (1.4 +/- 1.2 pH?min/kg) and the 3 with the highest values (23.9 +/-
      7.4 pH?min/kg) were classified as AR and AS, respectively, and used in the
      subsequent study. The steers were force-fed a diet containing 85% grain at 60% of
      the expected daily intake (5.8 +/- 0.8 and 5.6 +/- 0.6 kg for AR and AS,
      respectively) within 30 min. Mean ruminal pH over the postprandial 6-h period was
      higher for AR compared with AS (6.02 vs. 5.55), and mean total VFA concentration
      was 74% for AR compared with AS (122 vs. 164 mM). Molar proportion of butyrate in
      the ruminal fluid was 139% higher for AR compared with AS (17.5 vs. 7.33 mol/100
      mol of VFA). Expression of monocarboxylate cotransporter isoform 1, sodium
      hydrogen exchanger isoforms 1 and 2, and anion exchangers (downregulated in
      adenoma and putative anion exchanger, isoform 1) did not differ between AR and AS
      steers. However, expression of sodium hydrogen exchanger isoform 3, which imports
      Na(+) to the epithelial cell and exports H(+) to the rumen, was 176% higher in AR
      steers than in AS steers. Higher ruminal pH for AR might be partly due to a
      faster rate of VFA absorption, lower VFA production, or both.

PMID- 22863096
TI  - Safety of a probiotic cheese containing Lactobacillus plantarum Tensia according
      to a variety of health indices in different age groups.
AB  - Safety of the probiotic Lactobacillus plantarum strain Tensia (DSM 21380) was
      tested in vitro, in semihard Edam-type cheese, in an animal model and after
      consumption of the probiotic cheese in double-blind randomized placebo-controlled
      human intervention studies with different age groups. The susceptibility of L.
      plantarum Tensia to 8 antibiotics, and the presence of tetracycline (tet M, S, O,
      K, L) genes and class 1 integron was assessed by applying epsilometer-test and
      PCR-based methods. Production of biogenic amines by the probiotic strain in
      decarboxylation medium containing 1% of l-histidine, l-glutamine, l-ornithine, l
      arginine, or l-lysine and in cheese was tested by gas chromatography. The
      biosafety of L. plantarum Tensia was evaluated on National Institutes of Health
      line mice fed cheese containing Tensia at a concentration of 9.6 log cfu/g for 30
      consecutive days. In human intervention trials in adults and the elderly, the
      effects of different doses of Edam-type cheese and the probiotic bacterium on BW,
      gut functionality indices, and host metabolism were evaluated. The strain L.
      plantarum Tensia was susceptible to all tested antibiotics and did not possess
      the tetracycline resistance-determining genes tet(L), tet(S) and tet(O), nor did
      it contain the integron (Int1) gene. However, the strain was tet(K) and tet(M)
      positive. Lactobacillus plantarum Tensia did not produce potentially harmful
      biogenic amines, such as histamine or cadaverine. The amount of tyramine produced
      in the cheese environment during ripening and after 15 wk of storage was below
      the clinically significant content. In the animal model, no translocation of the
      administered strain or other microbes into the blood or organs of mice was
      detected. No harmful effect was observed on body mass index, inflammatory
      markers, or serum lipidograms during human intervention trials with different age
      groups at a daily dose of 10.3 or 8.17 log cfu/serving for 3 wk. No negative
      effect on gastrointestinal welfare was observed, but the consumption of 100g/d
      for 3 wk caused hard stools from the second week of the trial. The content of
      total lactobacilli increased in feces, and the presence of the ingested probiotic
      strain was confirmed after the consumption of cheese. Thus, L. plantarum strain
      Tensia is suitable for generally recognized as safe (GRAS) and qualified
      presumption of safety (QPS) criteria because it did not have any undesirable
      characteristics. The regular semihard Edam-type cheese (fat content of 26%) with
      the probiotic additive at a daily dose of 50 g or in excess (100g) and with a
      probiotic daily dose of 10 log cfu for 3 wk was safe.

PMID- 22863097
TI  - Invited review: milk production and reproductive performance: modern
      interdisciplinary insights into an enduring axiom.
AB  - A general belief across the dairy community, both scientific and commercial, is
      that of an antagonistic association between milk production and reproductive
      performance of dairy cows. In this article, we critically review the evidence
      supporting this belief and discuss some of its limitations. Based on the
      fundamental principles of experimental design and inference, we consider relevant
      issues that, although critical to the very foundation of the perceived production
      reproduction antagonism, seem to have been previously misrepresented or
      overlooked. In particular, we focus on issues of confounding, randomization,
      nature of inference, single- versus multiple-trait modeling, cow- versus herd
      level modeling, and scope of inference, all within the context of dairy
      production systems. Taken together, these issues indicate that the production
      reproduction antagonism may not be as pervasive as previously believed,
      suggesting the need for more rigorous methods of scientific investigation on this
      matter. We revisit the association between milk production and reproductive
      performance using a novel interdisciplinary approach based on cutting-edge
      statistical methods that accommodate some of the unique and previously ignored
      features of this problem. In fact, recent work supports a highly heterogeneous
      association between milk production and reproductive performance, whereby
      heterogeneity is partitioned across several scales and driven by many
      contributing factors, both physiological and managerial. We conclude that the
      relationship between milk production and reproductive performance is not
      necessarily that of a universal homogeneous antagonism and suggest better ways to
      study and even manage this association. A more comprehensive assessment that
      draws expertise from multiple scientific disciplines will be required to elicit
      management recommendations targeted to effectively optimize overall performance
      of dairy cows and commercial herds.

PMID- 22863098
TI  - Bioeconomic modeling of intervention against clinical mastitis caused by
      contagious pathogens.
AB  - The objective of this study was to assess the epidemiologic and economic
      consequences of intervention against contagious clinical mastitis during
      lactation. A bioeconomic model of intramammary infections (IMI) was used to
      simulate contagious spread of Staphylococcus aureus, Streptococcus uberis, and
      Streptococcus dysgalactiae, and an environmental spread of Escherichia coli IMI
      in a 100-cow dairy herd during 1 quota year. The costs of clinical IMI,
      subclinical IMI, and intervention were calculated into the total annual net costs
      of IMI during lactation per scenario and compared with a default scenario. Input
      parameter values were based on the scientific literature. The scenarios were 3-d
      intramammary lactational treatment (default), 5-d intramammary treatment, 5-d
      intramammary treatment and 3-d systemic treatment, 3-d intramammary treatment and
      culling bacteriologically unrecovered clinical IMI cows, and 5-d intramammary
      treatment and culling bacteriologically unrecovered clinical IMI cows.
      Sensitivity analysis was conducted on parameter input values. The results showed
      that interventions including antibiotic treatment combined with culling
      unrecovered clinical IMI cows resulted in the lowest transmission, number of IMI
      cases, and persistent subclinical IMI cases. Nonetheless, the high associated
      costs of culling bacteriologically unrecovered clinical IMI cows made the other
      scenarios with a long and intensive antibiotic treatment, but without culling,
      the most cost effective. The model was sensitive to changes to the cure rate of
      clinical IMI following treatment, but the ranking of the intervention scenarios
      did not change. The model was most sensitive to the changes to the transmission
      rate of Staph. aureus. The ranking of the intervention scenarios changed at low
      transmission rate of this pathogen, in which the default scenario became the most
      cost-effective scenario. In case of high transmission of contagious IMI
      pathogens, long and intensive treatment of clinical IMI should be preceded by
      strategies that lower the transmission.

PMID- 22863099
TI  - Performance and metabolic responses of Holstein calves to supplemental chromium
      in colostrum and milk.
AB  - Twenty-two newborn Holstein female calves (BW = 39.7 +/- 0.40 kg) were used to
      investigate the effects of chromium-l-methionine (Cr-Met) supplementation of
      colostrum for 3d after birth and mature milk up to wk 8 on feed intake, growth
      performance, health status, and metabolic and endocrine traits. Calves were
      randomly assigned to 2 groups, each consisting of 11 animals: 1) control and 2)
      0.03 mg of supplemental Cr/kg of BW(0.75). Body weight, height at withers, and
      hearth girth were measured weekly. Dry matter intake, rectal temperature, fecal
      score, and respiratory score were recorded daily. Blood samples were collected at
      12, 24, and 72 h after birth, and then every week up to 8 wk. Chromium did not
      affect mean body weight, dry matter intake, and withers height, but it increased
      hearth girth and average daily gain, tended to increase final BW, and decreased
      feed conversion ratio. Respiration rate increased and fecal score decreased with
      Cr, and rectal temperature tended to decrease with Cr. No Cr * time interactions
      were observed for performance and health status results except for fecal score.
      Blood glucose, insulin, insulin-to-glucose ratio, insulin-like growth factor-I,
      total protein, and triiodothyronine were not affected, whereas blood beta
      hydroxybutyrate, nonesterified fatty acids, cholesterol, cortisol, and thyroxin
      were affected by Cr supplementation. Supplemental Cr-Met decreased blood beta
      hydroxybutyrate at 72 h and in wk 1, 3, 4, 5, and 6 and decreased blood
      nonesterified fatty acids at 12h and in wk 3, 4, and 5 after birth. Blood
      cholesterol decreased in all sampling times, except for 12h and wk 7. Chromium
      decreased blood cortisol at 24h and in wk 2, 4, and 8. In conclusion, the present
      results demonstrate the beneficial effects of colostrum and milk supplementation
      with Cr to improve the performance and metabolic status of newborn calves.

PMID- 22863100
TI  - Change of plasma volume, osmolality, and acid-base status in healthy calves after
      feeding of milk and water- and milk-based oral rehydration solutions.
AB  - Oral rehydration solutions (ORS) are a simple and cheap method to treat diarrheal
      dehydration and acidosis. To maintain the energy supply of diarrheic calves, it
      is necessary to continue milk feeding. Suckling of milk or milk-based or
      hypertonic water-based ORS produces a slower rate of abomasal emptying than
      suckling isotonic water-based ORS. The faster abomasal passage of isotonic water
      based ORS implies that efficacious electrolytes reach the gut more quickly,
      possibly providing a faster rate of rehydration. The aim of the study was to
      verify when and to what extent milk and water- and milk-based ORS increase plasma
      volume and affect plasma osmolality and acid-base status in healthy suckling
      calves. Eleven calves were fed with milk and with an ORS that was prepared in
      water or milk. Moreover, for one experiment, the calves remained fasting without
      suckling milk or ORS. During the experimental phase, the calves were deprived of
      water, hay, and concentrates. Blood samples were taken before and at various time
      points after feeding. Total plasma protein, osmolality, [Na(+)], [K(+)], [Cl(-)],
      and albumin were determined. In 6 of 11 experiments, blood gas analysis was also
      performed. The calculated change in plasma volume after feeding was assessed from
      the plasma protein concentration before feeding (P(t=0)) and the plasma protein
      concentration after feeding (P(t=x)): (P(t=0)- P(t=x)) * 100/P(t=x). Water- and
      milk-based ORS produced equal rates of plasma expansion in healthy calves. After
      milk feeding, the change in plasma volume was decelerated. Because of water
      influx, we did not observe a significant effect of feeding regimen on plasma
      osmolality. Acid-base status was little affected by feeding regimen. Feeding of
      milk-based ORS increased plasma strong ion difference, an alkaline response,
      which could potentially also reduce acidosis in calves suffering from diarrhea.

PMID- 22863101
TI  - Evaluation of propane flaming for reducing bacterial counts in sand bedding.
AB  - An experiment was conducted on a commercial dairy farm to determine the effects
      of propane flaming on bacterial populations of common environmental mastitis
      pathogens in recycled sand bedding. One row of freestalls was flamed within 12 h
      after recycled bedding was added to stalls and then daily for the next 6 d.
      Bedding in a control row of freestalls was untreated. Stalls received the same
      treatment for 3 consecutive weeks. After 3 wk, bedding treatments were changed
      between rows in a switchback design. The daily movement of the 760 degrees C
      propane-fueled flame at 3.2 km/h over the surface of recycled sand bedding in
      stalls had a positive effect by reducing mastitis pathogen loads at different
      depths of bedding in a pathogen-specific manner. The greatest reduction of
      mastitis pathogen populations by flaming was on the surface 25 mm of recycled
      sand. Reductions in bacterial counts in deeper layers were less consistent.
      Bacterial populations in both flamed and control sand bedding were lower on the
      surface 25 mm compared with sand at a depth of 50 to 75 mm. The effects of
      subsequent flaming of sand over a week also differed among pathogens. In general,
      mastitis pathogens were reduced the most on the day that recycled sand was added
      to stalls, and flaming was less effective as sand bedding was in stalls over a 6
      d period. The use of propane flaming of recycled sand was shown to have potential
      as a practice to control mastitis pathogen populations in bedding. The greatest
      advantage afforded by flaming was on the surface of bedding, with inconsistent
      effects deeper in the stalls. Flaming was more effective in controlling bacterial
      populations in fresh recycled sand than in sand after several days use

PMID- 22863102
TI  - Genetic correlations of days open with production traits and contents in milk of
      major fatty acids predicted by mid-infrared spectrometry.
AB  - The objective of this study was to estimate the genetic relationships between
      days open (DO) and both milk production traits and fatty acid (FA) content in
      milk predicted by mid-infrared spectrometry. The edited data set included 143,332
      FA and production test-day records and 29,792 DO records from 29,792 cows in
      1,170 herds. (Co)variances were estimated using a series of 2-trait models that
      included a random regression for milk production and FA traits. In contrast to
      the genetic correlations with fat content, those between DO and FA content in
      milk changed considerably over the lactation. The genetic correlations with DO
      for unsaturated FA, monounsaturated FA, long-chain FA, C18:0, and C18:1 cis-9
      were positive in early lactation but negative after 100 d in milk. For the other
      FA, genetic correlations with DO were negative across the whole lactation. At 5 d
      in milk, the genetic correlation between DO and C18:1 cis-9 was 0.39, whereas the
      genetic correlations between DO and C6:0 to C16:0 FA ranged from -0.37 to -0.23.
      These results substantiated the known relationship between fertility and energy
      balance status, explained by the release of long-chain FA in early lactation,
      from the mobilization of body fat reserves, and the consequent inhibition of de
      novo FA synthesis in the mammary gland. At 200 d in milk, the genetic
      correlations between DO and FA content ranged from -0.38 for C18:1 cis-9 to -0.03
      for C6:0. This research indicates an opportunity to use FA content in milk as an
      indicator trait to supplement the prediction of genetic merit for fertility.

PMID- 22863103
TI  - Effects of method of barley grain processing and source of supplemental dietary
      fat on duodenal nutrient flows, milk fatty acid profiles, and microbial protein
      synthesis in dairy cows.
AB  - The objective of this study was to determine the interactive effects of barley
      grain processing and source of supplemental fat on ruminal nutrient digestion,
      duodenal nutrient flow, microbial protein synthesis, and milk fatty acid (FA)
      profiles in dairy cows. Four Holstein cows (656 +/- 28 kg of BW; 80 +/- 12 d in
      milk) fitted with permanent ruminal and duodenal cannulas were used in a 4*4
      Latin square design with a 2*2 factorial arrangement of experimental treatments,
      in which barley was either dry-rolled (DRB) or pelleted (PB) and supplemented
      with full-fat canola seed (canola) or full-fat flaxseed (flaxseed). Cows fed DRB
      consumed 1.8 to 3.5 kg/d more dry matter compared with those fed PB. Mean ruminal
      pH was lower and the duration (min/d) and area (pH * min) of total ruminal
      acidosis (RA; ruminal pH <5.8), mild RA (5.8 >ruminal pH >5.5), and severe RA
      (5.5 >ruminal pH >5.2), and the duration of acute RA (ruminal pH <5.2) were
      greater in cows fed PB compared with those fed DRB. Milk yield was unaffected by
      diet. Milk fat content and yield were greater in cows fed DRB than in cows fed
      PB. Cows fed PB had greater duodenal flows of C18:1 trans, C18:1 cis, C18:2 trans
      9,trans-12, C18:2 trans-9,cis-12, C18:2 trans-11,cis-15, and C18:2 trans-10,cis
      12 compared with those fed DRB. Duodenal flows of C18:1 cis, C18:1 trans, total
      C18:1, C18:2n6, C18:2 cis-9,trans-11, C18:2 trans-10,cis-12, C18:2 trans-11,trans
      13, total conjugated linoleic acid (CLA), and C18:3n3 were greater in cows fed
      flaxseed compared with those fed canola. Milk concentrations of C18:3n3 and total
      CLA tended to be greater in cows fed PB compared with those fed DRB. When
      compared with cows fed canola, milk concentrations of C18:2 trans-11,cis-15,
      C18:2 cis-9,trans-11, C18:2 trans-11,trans-13, total CLA, and C18:3n3 were
      greater in cows fed flaxseed. Ruminal digestion of neutral detergent fiber and
      acid detergent fiber was greater in cows fed DRB compared with those fed PB.
      Duodenal flow of ammonia-N tended to be greater in cows fed PB compared with
      those fed DRB. Duodenal flow of nonammonia nonmicrobial N was greater in cows fed
      flaxseed compared with those fed canola; however, barley grain processing did not
      affect duodenal nonammonia nonmicrobial N flow. Duodenal flow of microbial
      nonammonia N and microbial efficiency were not affected by diet. In summary,
      barley grain processing and source of fat altered ruminal FA biohydrogenation,
      and this was reflected in changes in duodenal FA flow and milk FA profiles;
      however, ruminal microbial protein synthesis was unaltered.

PMID- 22863104
TI  - Rumen-protected lysine, methionine, and histidine increase milk protein yield in
      dairy cows fed a metabolizable protein-deficient diet.
AB  - The objective of this experiment was to evaluate the effect of supplementing a
      metabolizable protein (MP)-deficient diet with rumen-protected (RP) Lys, Met, and
      specifically His on dairy cow performance. The experiment was conducted for 12 wk
      with 48 Holstein cows. Following a 2-wk covariate period, cows were blocked by
      DIM and milk yield and randomly assigned to 1 of 4 diets, based on corn silage
      and alfalfa haylage: control, MP-adequate diet (ADMP; MP balance: +9 g/d); MP
      deficient diet (DMP; MP balance: -317 g/d); DMP supplemented with RPLys
      (AminoShure-L, Balchem Corp., New Hampton, NY) and RPMet (Mepron; Evonik
      Industries AG, Hanau, Germany; DMPLM); and DMPLM supplemented with an
      experimental RPHis preparation (DMPLMH). The analyzed crude protein content of
      the ADMP and DMP diets was 15.7 and 13.5 to 13.6%, respectively. The apparent
      total-tract digestibility of all measured nutrients, plasma urea-N, and urinary N
      excretion were decreased by the DMP diets compared with ADMP. Milk N secretion as
      a proportion of N intake was greater for the DMP diets compared with ADMP.
      Compared with ADMP, dry matter intake (DMI) tended to be lower for DMP, but was
      similar for DMPLM and DMPLMH (24.5, 23.0, 23.7, and 24.3 kg/d, respectively).
      Milk yield was decreased by DMP (35.2 kg/d), but was similar to ADMP (38.8 kg/d)
      for DMPLM and DMPLMH (36.9 and 38.5kg/d, respectively), paralleling the trend in
      DMI. The National Research Council 2001model underpredicted milk yield of the DMP
      cows by an average (+/-SE) of 10.3 +/- 0.75 kg/d. Milk fat and true protein
      content did not differ among treatments, but milk protein yield was increased by
      DMPLM and DMPLMH compared with DMP and was not different from ADMP. Plasma
      essential amino acids (AA), Lys, and His were lower for DMP compared with ADMP.
      Supplementation of the DMP diets with RP AA increased plasma Lys, Met, and His.
      In conclusion, MP deficiency, approximately 15% below the National Research
      Council requirements from 2001, decreased DMI and milk yield in dairy cows.
      Supplementation of the MP-deficient diet with RPLys and RPMet diminished the
      difference in DMI and milk yield compared with ADMP and additional
      supplementation with RPHis eliminated it. As total-tract fiber digestibility was
      decreased with the DMP diets, but DMI tended to increase with RP AA
      supplementation, we propose that, similar to monogastric species, AA play a role
      in DMI regulation in dairy cows. Our data implicate His as a limiting AA in high
      producing dairy cows fed corn silage- and alfalfa haylage-based diets, deficient
      in MP. The MP-deficient diets clearly increased milk N efficiency and decreased
      dramatically urinary N losses.

PMID- 22863105
TI  - Effects of adding a concentrated pomegranate-residue extract to the ration of
      lactating cows on in vivo digestibility and profile of rumen bacterial
      population.
AB  - This study characterizes the effects of concentrated pomegranate-peel extract
      (CPE) addition to the TMR at levels of 1, 2, or 4% on voluntary intake, in vivo
      digestibility, milk yield and composition, and profile of rumen bacterial and
      archaeal populations in lactating Holstein cows. Supplementation of CPE
      significantly affected the abundance of methanogenic archaea and specific ruminal
      bacterial species related to cellulolytic activities and soluble sugar and lactic
      acid fermentation, as revealed by real-time PCR quantification. Furthermore, CPE
      supplementation had a significant dose-dependent effect on the whole ruminal
      bacterial community, as determined by automated ribosomal intergenic spacer
      analysis. These changes were accompanied by a significant increase in
      digestibility of dry matter, crude protein, and neutral detergent fiber, as well
      as milk and energy-corrected milk yields in cows fed the 4% CPE supplement. These
      results suggest that CPE supplementation significantly affects the rumen
      bacterial communities, which in turn may be related to a beneficial effect on
      dairy cow performance.

PMID- 22863106
TI  - Does milk treatment before cheesemaking affect microbial and chemical traits of
      ripened cheese? Grana Trentino as a case study.
AB  - The aim of this study was to evaluate the influence of different storage
      temperatures and delivery system of the milk on the microbiological and
      physicochemical characteristics of Grana Trentino, a long-ripened hard-cooked
      Italian cheese. In particular, 3 kinds of milk storage and delivery were studied:
      milk delivered to the dairy in the traditional manner without temperature
      control, milk delivered at 18 degrees C, and milk stored at the farm and
      delivered at 12 degrees C. Milk, natural whey starter, and cheeses after 18 mo of
      ripening were sampled for microbiological profiles, physicochemical analysis, and
      proteolysis evaluation, and a study of cheese volatile compounds through a solid
      phase microextraction gas chromatography-mass spectrometry technique was
      performed. Milk microbiota was not affected by any of the treatments. At the end
      of ripening, free fatty acid and ester contents were significantly higher in
      cheeses from milk without temperature control. This was probably due to the milk
      delivery to the dairy in churns causing the fat globule membrane break during
      transport and, consequently, a greater release of fat and deeper lipolysis. Milk
      refrigeration at 12 degrees C for 12h before delivery affected the distribution
      of nitrogen fractions in cheeses. Lower temperatures of milk storage favored a
      larger soluble nitrogen fraction and greater cheese proteolysis, probably caused
      by an enhanced plasmin activity. From this work, it is concluded that both milk
      temperature storage and transport system could affect cheese ripening, leading to
      significant differences in chemical compounds: if milk was delivered by churns,
      higher free fatty acid and ester content in cheeses was observed; if milk was
      stored at 12 degrees C for 12h before delivery, greater cheese proteolysis was
      induced with consequent faster ripening.

PMID- 22863107
TI  - Exposures to war-related traumatic events and post-traumatic stress disorder
      symptoms among displaced Darfuri female university students: an exploratory
      study.
AB  - BACKGROUND: With the deaths of hundreds of thousands and the displacement of up
      to three million Darfuris, the increasingly complex and on-going war in Darfur
      has warranted the need to investigate war-related severity and current mental
      health levels amongst its civilian population. The purpose of this study is to
      explore the association between war-related exposures and assess post-traumatic
      stress disorder (PTSD) symptoms amongst a sample of Darfuri female university
      students at Ahfad University for Women (AUW) in Omdurman city. METHODS: An
      exploratory cross-sectional study among a representative sample of Darfuri female
      university students at AUW (N = 123) was conducted in February 2010. Using an
      adapted version of the Harvard Trauma Questionnaire (HTQ), war-related exposures
      and post-traumatic stress disorder (PTSD) symptoms were assessed. Means and
      standard deviations illustrated the experiential severity of war exposure
      dimensions and PTSD symptom sub-scales, while Pearson correlations tested for the
      strength of association between dimensions of war exposures and PTSD symptom sub
      scales. RESULTS: Approximately 42 % of the Darfuri participants reported being
      displaced and 54 % have experienced war-related traumatic exposures either as
      victims or as witnesses (M = 28, SD = 14.24, range 0 - 40 events). Also, there
      was a strong association between the experiential dimension of war-related trauma
      exposures and the full symptom of PTSD. Moreover, the refugee-specific self
      perception of functioning sub-scale within the PTSD measurement scored a mean of
      3.2 (SD = .56), well above the 2.0 cut-off. CONCLUSIONS: This study provides
      evidence for a relationship between traumatic war-related exposures and symptom
      rates of PTSD among AUW Darfuri female students. Findings are discussed in terms
      of AUW counseling service improvement.

PMID- 22863109
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology National Cardiovascular Journals.
AB  - Disclosure of potential conflicts of interest (COI) is used by biomedical
      journals to guarantee credibility and transparency of the scientific process.
      Conflict of interest disclosure, however, is not systematically nor consistently
      dealt with by journals. Recent joint editorial efforts paved the way towards the
      implementation of uniform vehicles for COI disclosure. This paper provides a
      comprehensive editorial perspective on classical COI-related issues. New insights
      into the current COI policies and practices among European Society of Cardiology
      National Cardiovascular Journals, as derived from a cross-sectional survey using
      a standardised questionnaire, are discussed.

PMID- 22863110
TI  - Incidence, risk factors and causes of death in an HIV care programme with a large
      proportion of injecting drug users.
AB  - OBJECTIVES: To identify factors influencing mortality in an HIV programme
      providing care to large numbers of injecting drug users (IDUs) and patients co
      infected with hepatitis C (HCV). METHODS: A longitudinal analysis of monitoring
      data from HIV-infected adults who started antiretroviral therapy (ART) between
      2003 and 2009 was performed. Mortality and programme attrition rates within 2
      years of ART initiation were estimated. Associations with individual-level
      factors were assessed with multivariable Cox and piece-wise Cox regression.
      RESULTS: A total of 1671 person-years of follow-up from 1014 individuals was
      analysed. Thirty-four percent of patients were women and 33% were current or ex
      IDUs. 36.2% of patients (90.8% of IDUs) were co-infected with HCV. Two-year all
      cause mortality rate was 5.4 per 100 person-years (95% CI, 4.4-6.7). Most HIV
      related deaths occurred within 6 months of ART start (36, 67.9%), but only 5
      (25.0%) non-HIV-related deaths were recorded during this period. Mortality was
      higher in older patients (HR = 2.50; 95% CI, 1.42-4.40 for >=40 compared to 15-29
      years), and in those with initial BMI < 18.5 kg/m(2) (HR = 3.38; 95% CI, 1.82
      5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47-10.65 during the
      second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54
      13.41 for <100 compared to >=100 cells/MUl). Risk of death was not associated
      with IDU status (P = 0.38). CONCLUSION: Increased mortality was associated with
      late presentation of patients. In this programme, death rates were similar
      regardless of injection drug exposure, supporting the notion that satisfactory
      treatment outcomes can be achieved when comprehensive care is provided to these
      patients.

PMID- 22863111
TI  - Design of a novel antimicrobial peptide activated by virulent proteases.
AB  - Antimicrobial peptides are promising antibiotics as they possess strong
      antimicrobial activity and very broad spectra of activity. However,
      administration of an antibiotic with a very broad spectrum of activity disrupts
      normal microflora and increases the risks of other fatal infections. To solve the
      problem, we designed a novel antimicrobial peptide that is activated by virulent
      proteases of pathogenic organisms. We constructed a peptide composed of three
      domains, namely an antimicrobial peptide (lactoferricin) as the active center, a
      protective peptide (magainin intervening sequence) that suppresses antimicrobial
      activity, and a specific linker that joins these two components and is
      efficiently cleaved by virulent proteases. We utilized Candida albicans as a
      model organism that produces secreted aspartic proteases as a virulence
      attribute. We screened for a peptide sequence efficiently cleaved by secreted
      aspartic proteases isozymes and identified a GFIKAFPK peptide as the most
      favorable substrate. Subsequently, we chemically synthesized a peptide containing
      the GFIKAFPK sequence. The designed peptide possessed no antimicrobial activity
      until it was activated by secreted aspartic proteases isozymes. Furthermore, it
      demonstrated selective antimicrobial activity against C. albicans, but not
      against Saccharomyces cerevisiae. A designed peptide like the one described in
      this study may protect normal microflora, resulting in enhanced safety as a
      therapeutic.

PMID- 22863112
TI  - Cell-type specificity of ChIP-predicted transcription factor binding sites.
AB  - BACKGROUND: Context-dependent transcription factor (TF) binding is one reason for
      differences in gene expression patterns between different cellular states.
      Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq)
      identifies genome-wide TF binding sites for one particular context-the cells used
      in the experiment. But can such ChIP-seq data predict TF binding in other
      cellular contexts and is it possible to distinguish context-dependent from
      ubiquitous TF binding? RESULTS: We compared ChIP-seq data on TF binding for
      multiple TFs in two different cell types and found that on average only a third
      of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks
      occur more frequently in certain genomic contexts, such as CpG-rich promoters,
      whereas chromatin differences characterize cell-type specific TF binding. We also
      find, however, that genotype differences between the cell types can explain
      differences in binding. Moreover, ChIP-seq signal intensity and peak clustering
      are the strongest predictors of common peaks. Compared with strong peaks located
      in regions containing peaks for multiple transcription factors, weak and isolated
      peaks are less common between the cell types and are less associated with data
      that indicate regulatory activity. CONCLUSIONS: Together, the results suggest
      that experimental noise is prevalent among weak peaks, whereas strong and
      clustered peaks represent high-confidence binding events that often occur in
      other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered
      peaks show context-dependent regulation. We show that by combining signal
      intensity with additional data-ranging from context independent information such
      as binding site conservation and position weight matrix scores to context
      dependent chromatin structure-we can predict whether a ChIP-seq peak is likely to
      be present in other cellular contexts.

PMID- 22863114
TI  - The effect of Lactobacillus brevis KB290 against irritable bowel syndrome: a
      placebo-controlled double-blind crossover trial.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder of the
      digestive tract that causes chronic abdominal symptoms. We evaluated the effects
      of Lactobacillus brevis KB290 (KB290), which has been demonstrated to be
      effective at improving bowel movements and the composition of intestinal
      microflora, on IBS symptoms. METHODS: We performed a placebo control double-blind
      cross matched trial. Thirty-five males and females (aged 6 years and above) who
      had been diagnosed with IBS according to the Rome III criteria were divided into
      2 groups, and after a 4-week pre-trial observation period, they were administered
      test capsules containing KB290 or placebo for 4 weeks (consumption period I).
      Then, the capsule administration was suspended for 4 weeks in both groups
      (washout period), before the opposite capsules were administered for a further 4
      weeks (consumption period II). Fecal samples were collected on the first day of
      the pre-consumption observation period, the last day of consumption period I, the
      last day of the washout period, and the last day of consumption period II. In
      addition, the subjects' IBS symptoms and quality of life (QOL) and any adverse
      events that they experienced were evaluated. RESULTS: No significant difference
      in IBS symptoms was noted among the various periods. However, the mean QOL scores
      were improved during the test capsule consumption.The frequencies of watery and
      mushy feces were significantly lower in the test capsule consumption period than
      during the pre-consumption observation period, and the frequency of abdominal
      pain was significantly reduced in the test capsule consumption period compared
      with the other periods.The frequency of the genus Bifidobacterium was
      significantly higher, and that of the genus Clostridium was significantly lower,
      after the test capsule consumption than after the placebo consumption. The
      frequencies of the genera Lactobacillus, Bacteroides, and Enterococcus were also
      investigated, but no differences in their frequencies were detected between the
      placebo and test capsule consumption periods. CONCLUSIONS: Probiotics, the safety
      of which has been established, are used widely in various foods and can now be
      purchased readily. The results of the present study suggest that KB290 is useful
      for early intervention in IBS.

PMID- 22863113
TI  - Detection of P. aeruginosa  harboring bla CTX-M-2, bla GES-1 and bla GES-5, bla
      IMP-1 and bla SPM-1 causing infections in Brazilian tertiary-care hospital.
AB  - BACKGROUND: Nosocomial infections caused by Pseudomonas aeruginosa presenting
      resistance to beta-lactam drugs are one of the most challenging targets for
      antimicrobial therapy, leading to substantial increase in mortality rates in
      hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms
      of resistance, such as production of metallo-beta-lactamase (MBLs) and extended
      spectrum beta-lactamases (ESBLs) have the highest clinical impact. Hence, this
      study was designed to investigate the presence of genes codifying for MBLs and
      ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed
      teaching tertiary care hospital. METHODS: Fifty-six carbapenem-resistant P.
      aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains
      presenting MBL and/or ESBL genes were submitted to pulsed-field gel
      electrophoresis for genetic similarity evaluation. RESULTS: Despite the
      carbapenem resistance, genes for MBLs (blaSPM-1 or blaIMP-1) were detected in
      only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates.
      The blaCTX-M-2 was the most prevalent ESBL gene (19.6%), followed by blaGES-1 and
      blaGES-5 detected in one isolate each. In all isolates presenting MBL phenotype
      by double-disc synergy test (DDST), the blaSPM-1 or blaIMP-1 genes were detected.
      In addition, blaIMP-1 was also detected in three isolates which did not display
      any MBL phenotype. These isolates also presented the blaCTX-M-2 gene. The co
      existence of blaCTX-M-2 with blaIMP-1 is presently reported for the first time,
      as like as co-existence of blaGES-1 with blaIMP-1. CONCLUSIONS: In this study
      MBLs production was not the major mechanism of resistance to carbapenems,
      suggesting the occurrence of multidrug efflux pumps, reduction in porin channels
      and production of other beta-lactamases. The detection of blaCTX-M-2,blaGES-1 and
      blaGES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P.
      aeruginosa and the extraordinary ability presented by this pathogen to acquire
      multiple resistance mechanisms. These findings raise the concern about the future
      of antimicrobial therapy and the capability of clinical laboratories to detect
      resistant strains, since simultaneous production of MBLs and ESBLs is known to
      promote further complexity in phenotypic detection. Occurrence of intra-hospital
      clonal dissemination enhances the necessity of better observance of infection
      control practices.

PMID- 22863115
TI  - Target-induced structure-switching DNA hairpins for sensitive electrochemical
      monitoring of mercury (II).
AB  - A simple, sensitive and reusable electrochemical sensor was designed for
      determination of mercury (II) (Hg(2+)) by coupling target-induced conformational
      switch of DNA hairpins with thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination
      chemistry. The hairpin probe consisted of a stem of 6 base pairs enclosing a 14
      nucleotide (nt) loop and an additional 12 nt sticky end at the 3' end. Each
      hairpin was labeled with ferrocene (Fc) redox tag in the middle of the loop,
      which was immobilized on the electrode via self-assembly of the terminal thiol
      moiety at the 5' end. In the presence of target analyte, Hg(2+)-mediated base
      pairs induced the conformational change from the sticky end to open the hairpins,
      resulting in the ferrocene tags close to the electrode for the increasing redox
      current. The strong coordination reaction of T-Hg(2+)-T resulted in a good
      repeatability and intermediate precision down to 10%. The dynamic concentration
      range spanned from 5.0nM to 1.0MUM Hg(2+) with a detection limit of 2.5nM at the
      3s(blank) level. The strategy afforded exquisite selectivity for Hg(2+) against
      other environmentally related metal ions. Inspiringly, the developed sensor could
      be reused by introduction of iodide (I(-)).

PMID- 22863116
TI  - Real time monitoring of thrombin interactions with its aptamers: insights into
      the sandwich complex formation.
AB  - Aptamers are raising an increasing interest for biosensor applications as
      replacements for antibodies due to their high stability and low cost. Thrombin, a
      key enzyme in the coagulation cascade, is an archetypical target against which
      two different aptamers, binding to two different exosites, have been selected.
      Recent studies dedicated to thrombin monitoring applications of biosensors have
      taken advantage of a potential sandwich-like structure between thrombin and these
      two aptamers for amplification purposes. However, in most cases, only end-point
      analysis was observed as a result of labeling requirements, thus preventing
      access to the kinetics of the complex formation. By using Surface Plasmon
      Resonance (SPR) imaging of aptamer-functionalized biosensors, we followed the
      binding of thrombin on the sensor and its interaction with a second reporter
      aptamer in real-time and in a label-free manner. Surprisingly, we showed that the
      injection of a second unlabeled-aptamer following the previous thrombin injection
      destabilized the thrombin-aptamer complex formed on the sensor surface, thus
      limiting any further amplification. However, the direct co-injection of thrombin,
      pre-complexed with a biotinylated aptamer bound to streptavidin efficiently
      increased the SPR signal by comparison to single thrombin detection. The various
      injection sequences performed may be rationalized considering a poor selectivity
      of one of the aptamers towards its exosite and a further negative allosteric
      effect upon sandwich complexation of the thrombin with its aptamers.

PMID- 22863117
TI  - Real-time label-free monitoring of the cellular response to osmotic stress using
      conventional and long-range surface plasmons.
AB  - Cell volume and its regulation are key factors for cellular integrity and also
      serve as indicators of various cell pathologies. SPR sensors represent an
      efficient tool for real-time and label-free observations of changes in cell
      volume and shape. Here, we extend this concept by employing the use of long-range
      surface plasmons (LRSP). Due to the enhanced penetration depth of LRSP (~1MUm,
      compared to ~0.4MUm of a conventional surface plasmon), the observation of
      refractive index changes occurring deeper inside the cells is possible. In this
      work, the responses of a confluent normal rat kidney (NRK) epithelial cell layer
      to osmotic stress are studied by both conventional and long-range surface
      plasmons. Experiments are conducted in parallel using cell layers grown and
      stimulated under the same conditions to enable direct comparison of the results
      and discrimination of the osmotic stress-induced effects in different parts of
      the cell.

PMID- 22863118
TI  - Cell-phone-based measurement of TSH using Mie scatter optimized lateral flow
      assays.
AB  - Semi-quantitative thyr oid stimulating hormone (TSH) lateral flow
      immunochromatographic assays (LFA) are used to screen for serum TSH concentration
      >5 mIUL(-1) (hypothyroidism). The LFA format, however, is unable to measure TSH
      in the normal range or detect suppressed levels of TSH (<0.4 mIU L(-1);
      hyperthyroidism). In fact, it does not provide quantitative TSH values at all.
      Obtaining quantitative TSH results, especially in the low concentration range,
      has until now required the use of centralized clinical laboratories which require
      specimen transport, specialized equipment and personnel, and result in increased
      cost and delays in the timely reporting of important clinical results. We have
      conducted a series of experiments to develop and validate an optical system and
      image analysis algorithm based upon a cell phone platform. It is able to provide
      point-of-care quantitative TSH results with a high level of sensitivity and
      reproducibility comparable to that of a clinical laboratory-based third
      generation TSH immunoassay. Our research approach uses the methodology of the
      optimized Rayleigh/Mie scatter detection by taking into consideration the optical
      characteristics of a nitrocellulose membrane and gold nanoparticles on an LFA for
      quantifying TSH levels. Using a miniature spectrometer, LED light source, and
      optical fibers on a rotating benchtop apparatus, the light intensity from
      different angles of incident light and angles of detection to the LFA were
      measured. The optimum angles were found that the minimized Mie scattering from
      nitrocellulose membrane, consequently maximizes the Rayleigh scatter detection
      from the gold nanoparticles in the LFA bands. Using the results from the benchtop
      apparatus, a cell-phone-based apparatus was designed which utilized the embedded
      flash in the cell phone camera as the light source, piped the light with an
      optical fiber from the flash through a collimating lens to illuminate the LFA.
      Quantification of TSH was performed in an iOS application directly on the phone
      and verified using the code written in MATLAB. The limit of detection of the
      system was determined to be 0.31 mIU L(-1) (never achieved before on an LFA
      format), below the commonly accepted minimum concentration of 0.4 mIU L(-1)
      indicating clinical significance of hyperthyroidism. The system was further
      evaluated using human serum showing an accurate and reproducible platform for
      rapid and point-of-care quantification of TSH using a cell phone.

PMID- 22863119
TI  - Manassantin B inhibits melanosome transport in melanocytes by disrupting the
      melanophilin-myosin Va interaction.
AB  - Human skin hyperpigmentation disorders occur when the synthesis and/or
      distribution of melanin increases. The distribution of melanin in the skin is
      achieved by melanosome transport and transfer. The transport of melanosomes, the
      organelles where melanin is made, in a melanocyte precedes the transfer of the
      melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by
      decreasing melanosome transport. In this study, we found that an extract of
      Saururus chinensis Baill (ESCB) and one of its components, manassantin B,
      inhibited melanosome transport in Melan-a melanocytes and normal human
      melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting
      the interaction between melanophilin and myosin Va. Manassantin B is neither a
      direct nor an indirect inhibitor of tyrosinase. The total melanin content was not
      reduced when melanosome transport was inhibited in a Melan-a melanocyte
      monoculture by manassantin B. Manassantin B decreased melanin content only when
      Melan-a melanocytes were co-cultured with SP-1 keratinocytes or stimulated by
      alpha-MSH. Therefore, we propose that specific inhibitors of melanosome
      transport, such as manassantin B, are potential candidate or lead compounds for
      the development of agents to treat undesirable hyperpigmentation of the skin.

PMID- 22863121
TI  - In vitro study assessing the antibacterial activity of three silver
      impregnated/coated mechanical valve needleless connectors after blood exposure.
AB  - This in vitro study's purpose was to assess antibacterial activity of 3 different
      connectors: V-Link (Baxter, Deerfield, IL), Ultrasite Ag (B. Braun, Bethlehem,
      PA), and MaxGuard (CareFusion, Ontario, CA), impregnated with silver
      nanoparticles after blood exposure. All 3 silver-coated/impregnated connectors
      grew Staphylococcus aureus and Staphylococcus epidermidis. Log reduction of
      bacteria was not significant (range, +0.19 to -1.82). There was substantial
      bacterial recovery from all 3 connectors (mean ranges, 2.09 * 10 to 4.00 * 10)
      indicating that, once blood comes in contact with silver-coated/impregnated
      needleless connectors, their antibacterial activity is significantly reduced.

PMID- 22863122
TI  - Determinants of hand hygiene noncompliance in intensive care units.
AB  - BACKGROUND: Hand hygiene (HH) is single most effective preventive measure for
      health care-associated infection, but compliance rates remain low. This study
      estimated HH compliance among health care workers (HCWs) and examined factors
      associated with noncompliance. METHODS: An observational study design was carried
      out in 5 intensive care units (ICUs) at the University Hospital in Riyadh, Saudi
      Arabia. Among 242 HCWs, a total of 3,940 HH opportunities were observed by 6
      trained medical interns and students. The World Health Organization's "Five
      Moments for Hand Hygiene" procedure was used as a basis for the observations.
      RESULTS: The overall observed noncompliance rate was 58%. The factors associated
      with noncompliance were HCW job title (physicians, odds ratio [OR], 2.8; 95%
      confidence interval [CI], 1.8-4.2; allied health professionals, OR, 2.9, 95% CI,
      1.9-4.6); working the a.m. shift (OR, 1.5; 95% CI, 1.3-1.8), working in a
      pediatric ICU (OR, 1.8; 95% CI, 1.5-2.2), and performance of HH before patient
      contact (OR, 4.5; 95% CI, 2.6-7.8). CONCLUSIONS: Overall HH noncompliance was
      high in ICUs of this hospital. The demanding ICU work setting was an important
      factor associated with noncompliance. HH compliance was highest among therapists
      and technicians because of fewer patient interactions and thus fewer HH
      noncompliance opportunities per person. Further studies on the relationship
      between work environment demands and HH compliance rates are needed.

PMID- 22863123
TI  - Extravascular transport of nanoparticles in solid tumors.

PMID- 22863120
TI  - Overlap between functional GI disorders and other functional syndromes: what are
      the underlying mechanisms?
AB  - BACKGROUND: Irritable bowel syndrome and other gastrointestinal (GI) and non-GI
      disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint
      disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue
      syndrome are known as functional pain syndromes. They commonly coexist within the
      same individual. The pathophysiologic mechanisms of these disorders are not well
      understood, but it has been hypothesized that they share a common pathogenesis.
      PURPOSE: The objective of this review is to discuss the proposed pathophysiologic
      mechanisms, which have been similarly studied in these conditions. These
      mechanisms include enhanced pain perception, altered regional brain activation,
      infectious etiologies, dysregulations in immune and neuroendocrine function, and
      genetic susceptibility. Studies suggest that these functional disorders are
      multifactorial, but factors which increase the vulnerability of developing these
      conditions are shared.

PMID- 22863124
TI  - Arachidonic acid supplementation during gestational, lactational and post-weaning
      periods prevents retinal degeneration induced in a rodent model.
AB  - Fatty acids and their derivatives play a role in the response to retinal injury.
      The effects of dietary arachidonic acid (AA) supplementation on N-methyl-N
      nitrosourea (MNU)-induced retinal degeneration was investigated in young Lewis
      rats during the gestational, lactational and post-weaning periods. Dams were fed
      0.1, 0.5 or 2.0% AA diets or a basal (< 0.01% AA) diet. On postnatal day 21 (at
      weaning), male pups received a single intraperitoneal injection of 50 mg MNU/kg
      or vehicle, and were fed the same diet as their mother for 7 d. Retinal apoptosis
      was analysed by the terminal deoxynucleotidyl transferase-mediated dUTP
      digoxigenin nick-end labelling (TUNEL) assay 24 h after the MNU treatment, and
      retinal morphology was examined 7 d post-MNU. Histologically, all rats that
      received MNU and were fed the basal and 0.1% AA diets developed retinal
      degeneration characterised by the loss of photoreceptor cells (disappearance of
      the outer nuclear layer and the photoreceptor layer) in the central retina. The
      0.5 and 2.0% AA diets rescued rats from retinal damage. Morphometrically, in
      parallel with the AA dose (0.5 and 2.0% AA), the photoreceptor ratio
      significantly increased and the retinal damage ratio decreased in the central
      retina, compared with the corresponding ratios in basal diet-fed rats. In
      parallel with the increase in serum and retinal AA levels and the AA:DHA ratio,
      the apoptotic index in the central retina was dose-dependently decreased in rats
      fed the 0.5 and 2.0% AA diets. In conclusion, an AA-rich diet during the
      gestation, lactation and post-weaning periods rescued young Lewis rats from MNU
      induced retinal degeneration via the inhibition of photoreceptor apoptosis.
      Therefore, an AA-enriched diet in the prenatal and postnatal periods may be an
      important strategy to suppress the degree of photoreceptor injury in humans.

PMID- 22863125
TI  - Educating dental students of the current generation.

PMID- 22863126
TI  - Management of high caries risk patients: part I--risk assessment.

PMID- 22863127
TI  - Esthetic and functional rehabilitation of a bilateral cleft palate patient with
      fixed prosthodontic therapy.
AB  - Patients with bilateral cleft lip and palate present with multiple challenges to
      the prosthodontist. Some of them include mobility of the premaxillary segment,
      multiple missing and malposed anterior teeth, unfavorable soft tissues, and a
      tense maxillary lip. This clinical report describes the fixed prosthodontic
      management of a bilateral cleft lip and palate patient with a surgically
      corrected lip and a mobile premaxillary segment. The patient presented with an 11
      unit metal-ceramic fixed partial denture made of a base metal alloy that was made
      25 years ago. He had multiple porcelain fractures over the years that compromised
      his esthetics and function. Prosthodontic therapy involved sectioning the old
      prosthesis, followed by careful treatment planning and fabrication of a new fixed
      dental prosthesis with improved design and superior materials. At a 3-year follow
      up, the fixed dental prosthesis remained intact and functional, and no further
      complications were noted. A discussion of approaches to treatment planning,
      biomechanical principles involved, and choice of biomaterials in designing a
      fixed prosthesis for such patients is presented. CLINICAL SIGNIFICANCE: As cleft
      palate patients require life-long prosthodontic follow-up and maintenance,
      revisional treatments should incorporate superior materials and methods to
      minimize future complications.

PMID- 22863128
TI  - Commentary. Esthetic and functional rehabilitation of a bilateral cleft palate
      patient with fixed prosthodontic therapy.

PMID- 22863129
TI  - An introduction to the implant crown with an esthetic adhesive margin (ICEAM).
AB  - This article describes a novel technique with the addition of a pressed porcelain
      abutment margin capable of bonding to the porcelain margin of an implant crown
      restoration. This allows for supragingival margin placement, reduces the
      potential effect of excess cement-induced peri-implant disease, and provides a
      controlled environment for the bonding process. Another advantage is the matching
      esthetics of the crown and supporting abutment, which in the event gingival
      recession occurs, the restoration appears as a longer tooth without the risk of
      exposing an underlying abutment margin with different esthetic properties.
      CLINICAL SIGNIFICANCE: The transition margin from an implant abutment to a crown
      is challenging to manage especially esthetically. Placing the abutment margin in
      a subgingival position helps hide the unesthetic transition, however, this
      reduces the ability to clean excess cement, increases the risk of peri-implant
      disease and the inability to control gingival sulcular fluids may affect the
      cement bond. The implant crown with an esthetic adhesive margin provides for
      supragingival bonded margins that can aid in complete removal of excess cement at
      the same time providing an esthetically pleasing result.

PMID- 22863130
TI  - Commentary. An introduction to the implant crown with an esthetic adhesive margin
      (ICEAM).

PMID- 22863131
TI  - Survival rates for porcelain laminate veneers with special reference to the
      effect of preparation in dentin: a literature review.
AB  - The porcelain laminate veneer is an elective restoration, often placed in the
      absence of disease for purely esthetic reasons. As such, it would appear
      desirable that the success rate of the technique was 100%. It is therefore the
      purpose of this paper to review the literature on porcelain laminate veneer
      survival by searching dental databases containing clinical trials of porcelain
      veneer restorations. References of selected trials were also screened to identify
      relevant studies. Each paper that was included was examined to ascertain if
      preparation into dentin affected survival. A total of 24 papers were included in
      the review. It was concluded that survival rates of porcelain laminate veneers
      are rarely 100%, and there is reasonable evidence indicating that a veneer
      preparation into dentin adversely affects survival. CLINICAL RELEVANCE: A review
      of the literature has indicated that porcelain laminate veneer survival is rarely
      100%. Accordingly, patients should be made aware of this before embarking on this
      elective restorative technique. Clinicians should also be aware that the ideal
      preparation for porcelain veneers remains within enamel.

PMID- 22863132
TI  - Commentary. Survival rates for porcelain laminate veneers with special reference
      to the effect of preparation in dentin: a literature review.

PMID- 22863133
TI  - Effect of a nano-hydroxyapatite paste on bleaching-related tooth sensitivity.
AB  - STATEMENT OF THE PROBLEM: Bleaching-related tooth sensitivity has been shown to
      be facilitated by the presence of enamel defects. A nano-hydroxyapatite (n-HAP)
      paste has been shown to repair these defects. PURPOSE OF THE STUDY: Using a
      randomized clinical trial, an n-HAP paste was investigated to determine its
      efficacy in reducing bleaching-related tooth sensitivity. METHODS AND MATERIALS:
      An n-HAP paste (Renamel AfterBleach, Sangi Co., Ltd., Tokyo, Japan) and a placebo
      (zero-HAP) were randomly assigned for use in 42 participants. A 7% hydrogen
      peroxide gel was used twice daily for 14 days, with use of assigned desensitizer
      for 5 minutes immediately following. A diary was completed daily for 4 weeks to
      note: use of the agents and sensitivity on a visual analog scale (VAS). Three
      aspects of tooth sensitivity were investigated: percentage of participants;
      number of days; and intensity level. Color change was assessed. RESULTS: For
      Groups zero-HAP and n-HAP, respectively, 51 and 29% of participants reported
      tooth sensitivity (p = 0.06). Days of sensitivity were 76 and 36, respectively (p
      = 0.001). Change in VAS score from baseline trended higher for group zero-HAP (p
      = 0.16). Color change was equivalent. DISCUSSION: The data trend indicated group
      n-HAP experienced less sensitivity over all three measures. Only the number of
      days of sensitivity was statistically significant. CONCLUSION: Within the limits
      of the study it can be concluded that the use of the n-HAP paste was associated
      with a statistically significant reduction in the number of days of tooth
      sensitivity experienced during active bleaching. CLINICAL RELEVANCE: For those
      using a tooth whitener without a desensitizing agent, this study indicates that a
      paste containing nano-hydroxyapatite crystal can effectively reduce the duration
      of tooth sensitivity.

PMID- 22863134
TI  - Commentary. Effect of a nano-hydroxyapatite paste on bleaching-related tooth
      sensitivity.

PMID- 22863135
TI  - The effect of ultrasonic instruments on the quality of preparation margins and
      bonding to dentin.
AB  - STATEMENT OF THE PROBLEM: Ultrasonic instruments have recently been developed for
      finishing crown preparations. They are successful in accessing difficult areas on
      the preparation margin, but their effects on the dentin surface and on bond
      strength are contradictory. PURPOSE: The aim was to evaluate the condition of
      crown preparation margins finished using new ultrasonic instruments and to assess
      their effects on dentin bond strength. METHODS: Characteristics of tooth surfaces
      prepared using two different ultrasonic protocols were compared; Perfect Margin
      Shoulder (PMS) (PMS 3, Satelec, Merignac, France) 1, 2, and 3 (complete
      finishing) versus PMS 1 and 2 (partial finishing). They were assessed using
      scanning electron microscopy (SEM) and surface roughness analysis. Bonding of
      composite resin to dentin surfaces prepared with the complete PMS kit was
      compared with dentin surfaces prepared with finishing diamond burs, using micro
      tensile testing. RESULTS: SEM images revealed a clear difference between the two
      preparation sequences (PMS 1, 2 versus PMS 1, 2, and 3). Surfaces finished using
      the PMS tips 1, 2, and 3 appeared continuous, even, and smooth compared with PMS
      tips 1 and 2 only. The additional use of the PMS 3 uncoated tip enhanced smear
      layer removal. There was no significant difference when comparing the surface
      roughness obtained with the PMS 1, 2, and 3 protocol with the PMS 1 and 2 only (p
      > 0.05). Micro-tensile bond strength was not significantly different between the
      surfaces prepared with the ultrasonic instruments and the surfaces prepared with
      the diamond burs (p > 0.05). CONCLUSION: The use of the complete PMS finishing
      kit (PMS 1, 2, and 3) produced better quality finishing lines than PMS 1 and 2.
      The use of ultrasonic instruments to prepare dentin resulted in comparable bond
      strengths to the use of diamond burs. CLINICAL SIGNIFICANCE: The extremely
      precise preparation margin possible with ultrasonic instruments improves the
      quality and accuracy of crown preparations, which may lead to better impressions
      and closer adaptation of restorations. The complete set of three Perfect Margin
      Shoulder instruments is recommended, which can produce comparable bond strengths
      to preparations with rotary instruments.

PMID- 22863136
TI  - Commentary. The effect of ultrasonic instruments on the quality of preparation
      margins and bonding to dentin.

PMID- 22863137
TI  - Critical appraisal. Self-adhesive resin cements--part II.

PMID- 22863138
TI  - Limited intervention improves technical skill in focus assessed transthoracic
      echocardiography among novice examiners.
AB  - BACKGROUND: Previous studies addressing teaching and learning in point-of-care
      ultrasound have primarily focussed on image interpretation and not on the
      technical quality of the images. We hypothesized that a limited intervention of
      10 supervised examinations would improve the technical skills in Focus Assessed
      Transthoracic Echocardiography (FATE) and that physicians with no experience in
      FATE would quickly adopt technical skills allowing for image quality suitable for
      interpretation. METHODS: Twenty-one physicians with no previous training in FATE
      or echocardiography (Novices) participated in the study and a reference group of
      three examiners with more than 10 years of experience in echocardiography
      (Experts) was included. Novices received an initial theoretical and practical
      introduction (2 hours), after which baseline examinations were performed on two
      healthy volunteers. Subsequently all physicians were scheduled to a separate
      intervention day comprising ten supervised FATE examinations. For effect
      measurement a second examination (evaluation) of the same two healthy volunteers
      from the baseline examination was performed. RESULTS: At baseline 86% of images
      obtained by novices were suitable for interpretation, on evaluation this was 93%
      (p = 0.005). 100% of images obtained by experts were suitable for interpretation.
      Mean global image rating on baseline examinations was 70.2 (CI 68.0-72.4) and
      mean global image rating after intervention was 75.0 (CI 72.9-77.0), p = 0.0002.
      In comparison, mean global image rating in the expert group was 89.8 (CI 88.8
      90.9). CONCLUSIONS: Improvement of technical skills in FATE can be achieved with
      a limited intervention and upon completion of intervention 93% of images achieved
      are suitable for clinical interpretation.

PMID- 22863139
TI  - Calpain inhibitor nanocrystals prepared using Nano Spray Dryer B-90.
AB  - The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the
      production of drug nanocrystals. Among attractive drugs, calpain inhibitor that
      inhibits programmed cell death 'apoptosis' is a candidate for curing apoptosis
      mediated intractable diseases such as Alzheimer's disease and Parkinson's
      disease. In this study, the preparation of calpain inhibitor nanocrystals using
      Nano Spray Dryer B-90 was demonstrated. The particle sizes were controlled by
      means of selecting mesh aperture sizes. The obtained average particle sizes were
      in the range of around 300 nm to submicron meter.

PMID- 22863140
TI  - Predictors of chronic food insecurity among adolescents in Southwest Ethiopia: a
      longitudinal study.
AB  - BACKGROUND: Evidence on the differential impacts of the global food crisis as it
      translates into chronic food insecurity locally is essential to design food
      security interventions targeting the most vulnerable population groups. There are
      no studies on the extent of chronic food insecurity or its predictors among
      adolescents in developing countries. In the context of increased food prices in
      Ethiopia, we hypothesized that adolescents in low income urban households are
      more likely to suffer from chronic food insecurity than those in the rural areas
      who may have direct access to agricultural products. METHODS: This report is
      based on data from the first two rounds of the Jimma Longitudinal Family Survey
      of Youth (JLFSY). Both adolescents and households were selected using a
      stratified random sampling method. A total of 1911 adolescents aged 13-17 years
      were interviewed on their personal experiences of food insecurity both at
      baseline and at year two. Multivariable logistic regression analyses were used to
      compare chronic adolescent food insecurity by household income, household food
      insecurity, and socio-demographic variables after one year of follow-up. RESULTS:
      Overall, 20.5% of adolescents were food insecure in the first round survey, while
      the proportion of adolescents with food insecurity increased to 48.4% one year
      later. During the one year follow up period, more than half (54.8%) of the youth
      encountered transient food insecurity - that is, either during the first or the
      second round survey. During the follow up period, 14.0% of adolescents had
      chronic food insecurity (i.e. were food insecure at both rounds). Multivariable
      logistic regression analysis showed that adolescents in the urban households with
      low (OR = 1.69, P = 0.008) and middle (OR = 1.80, P = 0.003) income tertiles were
      nearly twice as likely to suffer from chronic food insecurity compared with those
      in high income tertile, while this was not the case in rural and semi-urban
      households. Female sex of adolescents (P < 0.01), high dependency ratio (P <
      0.05) and household food insecurity (P < 0.001) were independent predictors of
      chronic adolescent food insecurity in urban, semi-urban, and rural areas, while
      educational status of the adolescents was negatively associated with chronic food
      insecurity (OR = 0.047, P = 0.002) in urban areas. CONCLUSIONS: In the context of
      increased food prices, household income is an independent predictor of chronic
      food insecurity only among adolescents in the low income, urban households.
      Female gender, educational status of primary or less and being a member of
      households with high dependency ratio were independent predictors of chronic food
      insecurity in urban, semi-urban, and rural areas. The fact that the prevalence of
      chronic food insecurity increased among adolescents who are members of
      chronically food insecure urban households as income tertiles decreased suggests
      that the resilience of buffering is eroded when purchasing power diminishes and
      food resources are dwindling. Food security interventions should target urban low
      income households to reduce the level of chronic food insecurity and its
      consequences.

PMID- 22863141
TI  - Oocyte-like cells induced from mouse spermatogonial stem cells.
AB  - BACKGROUND: During normal development primordial germ cells (PGCs) derived from
      the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs
      can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the
      presence of various growth factors. Several recent studies have now demonstrated
      that spermatogonial stem cells (SSCs) can also revert back to pluripotency as
      embryonic stem (ES)-like cells under certain culture conditions. However, the
      potential dedifferentiation of SSCs into PGCs or the potential generation of
      oocytes from SSCs has not been demonstrated before. RESULTS: We report that mouse
      male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived
      oocytes (SSC-Oocs) were similar in size to normal mouse mature oocytes. They
      expressed oocyte-specific markers and gave rise to embryos through
      parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in
      these SSC-Oocs were significantly down-regulated or turned off, while oocyte
      specific X-linked genes were activated. The gene expression profile appeared to
      switch to that of the oocyte across the X chromosome. Furthermore, these oocyte
      like cells lost paternal imprinting but acquired maternal imprinting.
      CONCLUSIONS: Our data demonstrate that SSCs might maintain the potential to be
      reprogrammed into oocytes with corresponding epigenetic reversals. This study
      provides not only further evidence for the remarkable plasticity of SSCs but also
      a potential system for dissecting molecular and epigenetic regulations in germ
      cell fate determination and imprinting establishment during gametogenesis.

PMID- 22863142
TI  - Genome-wide inference of transcription factor-DNA binding specificity in cell
      regeneration using a combination strategy.
AB  - The cell growth, development, and regeneration of tissue and organ are associated
      with a large number of gene regulation events, which are mediated in part by
      transcription factors (TFs) binding to cis-regulatory elements involved in the
      genome. Predicting the binding affinity and inferring the binding specificity of
      TF-DNA interactions at the genomic level would be fundamentally helpful for our
      understanding of the molecular mechanism and biological implication underlying
      sequence-specific TF-DNA recognition. In this study, we report the development of
      a combination method to characterize the interaction behavior of a 11-mer
      oligonucleotide segment and its mutations with the Gcn4p protein, a homodimeric,
      basic leucine zipper TF, and to predict the binding affinity and specificity of
      potential Gcn4p binders in the genome-wide scale. In this procedure, a position
      mutated energy matrix is created based on molecular modeling analysis of native
      and mutated Gcn4p-DNA complex structures to describe the position-independent
      interaction energy profile of Gcn4p with different nucleotide types at each
      position of the oligonucleotide, and the energy terms extracted from the matrix
      and their interactives are then correlated with experimentally measured
      affinities of 19268 distinct oligonucleotides using statistical modeling
      methodology. Subsequently, the best one of built regression models is
      successfully applied to screen those of potential high-affinity Gcn4p binders
      from the complete genome. The findings arising from this study are briefly listed
      below: (i) The 11 positions of oligonucleotides are highly interactive and non
      additive in contribution to Gcn4p-DNA binding affinity; (ii) Indirect
      conformational effects upon nucleotide mutations as well as associated subtle
      changes in interfacial atomic contacts, but not the direct nonbonded
      interactions, are primarily responsible for the sequence-specific recognition;
      (iii) The intrinsic synergistic effects among the sequence positions of
      oligonucleotides determine Gcn4p-DNA binding affinity and specificity; (iv)
      Linear regression models in conjunction with variable selection seem to perform
      fairly well in capturing the internal dependences hidden in the Gcn4p-DNA system,
      albeit ignoring nonlinear factors may lead the models to systematically
      underestimate and overestimate high- and low-affinity samples, respectively.

PMID- 22863143
TI  - Comparative analysis of the Oenococcus oeni pan genome reveals genetic diversity
      in industrially-relevant pathways.
AB  - BACKGROUND: Oenococcus oeni, a member of the lactic acid bacteria, is one of a
      limited number of microorganisms that not only survive, but actively proliferate
      in wine. It is also unusual as, unlike the majority of bacteria present in wine,
      it is beneficial to wine quality rather than causing spoilage. These benefits are
      realised primarily through catalysing malolactic fermentation, but also through
      imparting other positive sensory properties. However, many of these industrially
      important secondary attributes have been shown to be strain-dependent and their
      genetic basis it yet to be determined. RESULTS: In order to investigate the scale
      and scope of genetic variation in O. oeni, we have performed whole-genome
      sequencing on eleven strains of this bacterium, bringing the total number of
      strains for which genome sequences are available to fourteen. While any single
      strain of O. oeni was shown to contain around 1800 protein-coding genes, in-depth
      comparative annotation based on genomic synteny and protein orthology identified
      over 2800 orthologous open reading frames that comprise the pan genome of this
      species, and less than 1200 genes that make up the conserved genomic core present
      in all of the strains. The expansion of the pan genome relative to the coding
      potential of individual strains was shown to be due to the varied presence and
      location of multiple distinct bacteriophage sequences and also in various
      metabolic functions with potential impacts on the industrial performance of this
      species, including cell wall exopolysaccharide biosynthesis, sugar transport and
      utilisation and amino acid biosynthesis. CONCLUSIONS: By providing a large cohort
      of sequenced strains, this study provides a broad insight into the genetic
      variation present within O. oeni. This data is vital to understanding and
      harnessing the phenotypic variation present in this economically-important
      species.

PMID- 22863144
TI  - Evaluation of clinical, histological and immunological changes and qPCR detection
      of Mycoplasma hyopneumoniae in tissues during the early stages of mycoplasmal
      pneumonia in pigs after experimental challenge with two field isolates.
AB  - Differences in Mycoplasma hyopneumoniae strain virulence and infection patterns
      will affect experimental challenge systems used to evaluate vaccine efficacy. Two
      strains (Hillcrest and Beaufort) were assessed by experimental pig challenge for
      their ability to induce clinical and pathological lesions and cytokine responses.
      Tracheobronchial lavage fluid (TBLF) was collected before and 17-18 days after
      challenge with Hillcrest (n=8), Beaufort (n=8) or no organisms (n=3). Coughing
      was assessed twice daily, and at slaughter 21 (n=9) or 28 (n=10) days post
      challenge, gross and histopathology of lungs were quantified and a quantitative
      PCR (mhp183 qPCR) was applied to detect M. hyopneumoniae DNA in tissues and TBLF.
      Hillcrest was clearly superior to Beaufort in its ability to induce coughing and
      pneumonic lesions. At 17-18 days, interleukin (IL)-1beta and IL-6 concentrations
      in TBLF were only significantly higher (8.7 and 5.1 fold respectively) than
      controls (P<0.001) in Hillcrest-challenged pigs. Lungs of all Hillcrest
      challenged pigs were qPCR positive at either slaughter date, but only at day 28
      in Beaufort-challenged pigs. M. hyopneumoniae DNA was highest in concentration in
      lungs 21 days after Hillcrest challenge, and was detected in the spleen, kidney
      and/or liver of Hillcrest-challenged pigs, but not in Beaufort pigs. While M.
      hyopneumoniae DNA concentration in TBLF was elevated following Hillcrest and
      Beaufort challenge, there was no significant difference in mean mycoplasmal DNA
      concentration detected in TBLF from pigs challenged with either isolate (P>0.05).
      Thus a suitable challenge strain, coupled with lung pathology and cytokine
      assays, are valuable in assessing post-challenge responses. Assessment of M.
      hyopneumoniae DNA in lung and abdominal tissues by mhp183 qPCR, in conjunction
      with histopathology, were valuable in confirming M. hyopneumoniae infection.

PMID- 22863145
TI  - Short hairpin RNA targeting 2B gene of coxsackievirus B3 exhibits potential
      antiviral effects both in vitro and in vivo.
AB  - BACKGROUND: Coxsackievirus B3 is an important infectious agent of viral
      myocarditis, pancreatitis and aseptic meningitis, but there are no specific
      antiviral therapeutic reagents in clinical use. RNA interference-based technology
      has been developed to prevent the viral infection. METHODS: To evaluate the
      impact of RNA interference on viral replication, cytopathogenicity and animal
      survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B) expressed
      by a recombinant vector (pGCL-2B) or a recombinant lentivirus (Lenti-2B) were
      tansfected in HeLa cells or transduced in mice infected with CVB3. RESULTS: ShRNA
      2B exhibited a significant effect on inhibition of viral production in HeLa
      cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral
      tissues titers and attenuated tissue damage compared with those of the shRNA-NC
      treated control group. Lenti-2B displayed more effective role in inhibition of
      viral replication than pGCL-2B in vivo. CONCLUSIONS: Coxsackievirus B3 2B is an
      effective target of gene silencing against coxsackievirus B3 infection,
      suggesting that shRNA-2B is a potential agent for further development into a
      treatment for enterviral diseases.

PMID- 22863146
TI  - The potential use of allogeneic platelet-rich plasma for large bone defect
      treatment: immunogenicity and defect healing efficacy.
AB  - Autologous platelet-rich plasma (PRP) has been extensively investigated for large
      bone defect treatment, but its clinical application is harassed by controversial
      outcome, due to highly variable PRP quality among patients. Alternatively,
      allogeneic PRP from well-characterized donors cannot only generate more
      consistent and reliable therapeutic effect but also avoid harvesting large
      quantities of blood, an additional health burdens to patients. However, the use
      of allogeneic PRP for bone defect treatment is generally less investigated,
      especially for its immunogenicity in such application. Here, we meticulously
      investigated the immunogenicity of allogeneic PRP and evaluated its healing
      efficacy for critical-sized defect treatment. Allogeneic PRP contained 4.1-fold
      and 2.7- to 4.9-fold higher amount of platelets and growth factors than whole
      blood, respectively. The intramuscular injection of allogeneic PRP to rabbits did
      not trigger severe and chronic immunoresponse, evidenced by little change in
      muscular tissue microstructure and CD4+/CD8+ T lymphocyte subpopulation in
      peripheral blood. The implantation of allogeneic PRP/deproteinized bone matrix
      (DPB) constructs (PRP+DPB) successfully bridged 1.5-cm segmental radial defects
      in rabbits, achieving similar healing capacity as autologous MSC/DPB constructs
      (MSC+DPB), with greater bone formation (1.1-1.5*, p<0.05) and vascularization
      (1.3-1.6*, p<0.05) than DPB alone, shown by histomorphometric analysis, bone
      mineral density measurement, and radionuclide bone imaging. Furthermore, the
      implantation of both allogeneic PRP- and autologous MSC-mediated DPB constructs
      (PRP + MSC + DPB) resulted in the most robust bone regeneration (1.2-2.1*,
      p<0.05) and vascularization (1.3-2.0*, p<0.05) than others (PRP+DPB, MSC+DPB, or
      DPB alone). This study has demonstrated the promising use of allogeneic PRP for
      bone defect treatment with negligible immunogenicity, great healing efficacy,
      potentially more consistent quality, and no additional health burden to patients;
      additionally, the synergetic enhancing effect found between allogeneic PRP and
      autologous MSCs may shed a light on developing new therapeutic strategies for
      large bone defect treatment.

PMID- 22863147
TI  - The neuropeptide 26RFa is expressed in human prostate cancer and stimulates the
      neuroendocrine differentiation and the migration of androgeno-independent
      prostate cancer cells.
AB  - AIM: Accumulating data suggest that neuropeptides produced by neuroendocrine
      cells play a crucial role in the progression and aggressiveness of hormone
      refractory prostate cancer (CaP). In this study, we have investigated the
      presence and function of the neuropeptide 26RFa in CaP. METHODS: We have
      localised and quantified tumour cells containing 26RFa and its receptor, GPR103,
      in CaP sections of various grades. In vitro experiments were performed to
      investigate the effects of 26RFa on the migration, proliferation and
      neuroendocrine differentiation of the androgeno-independent (AI) prostate cancer
      cell line DU145. RESULTS: 26RFa and GPR103 are present in carcinomatous foci
      exhibiting a neuroendocrine differentiation, and the number of 26RFa and GPR103
      immunoreactive cancer cells increases with the grade of CaP. 26RFa stimulated the
      migration of native or transdifferentiated AI DU145 cells, but had no effect on
      their proliferation. Furthermore, 26RFa induced the neuroendocrine
      differentiation of DU145 cells as assessed by the occurrence of neurite-like
      extensions and the increase of the expression of the neuroendocrine marker
      chromogranin A. CONCLUSION: The present data indicate that 26RFa may participate
      to the development of CaP at the AI state by promoting the neuroendocrine
      differentiation and the migration of cancer cells via autocrine/paracrine
      mechanisms.

PMID- 22863149
TI  - Using a serosal trough for fashioning a continent catheterizable stoma: technique
      and outcomes.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Continent urinary
      diversion with bladder augmentation is an established method of providing urinary
      continence in children with bladder exstrophy, who are not suitable candidates or
      have a failed bladder neck reconstruction. Sub-mucosal implantation of the
      tubularized catheterizable stoma (usually the appendix) into the reservoir, with
      backing typically provided by either the bladder musculature or colonic taenia,
      is safe and highly effective in these children. In some cases of classic bladder
      exstrophy and in the majority of patients with cloacal exstrophy, the ileum is
      used for enterocystoplasty and therefore there is no taenia to back the implanted
      catheterizable channel. This study describes the steps for providing a reliable
      flap-valve mechanism for the continent catheterizable channel using the serosal
      trough technique. OBJECTIVES: To evaluate the efficacy and potential
      complications of the serosal-trough (ST) technique for the implantation of a
      continent catheterizable stoma (CCS) during enterocystoplasty. To describe the
      surgical technique and provide detailed illustrations. PATIENTS AND METHODS:
      Using an institutional review board-approved departmental database, children with
      bladder exstrophy, born after 1990, were selected, and patients who had undergone
      urinary diversion with a CCS created using the ST technique were identified.
      Demographic and technical characteristics, as well as the eventual clinical
      outcomes, were retrospectively reviewed. RESULTS: A total of 135 patients with
      urinary diversion were identified, of whom 26 (13 males) had undergone CCS
      implantation using the ST technique. Patients included 14 classic exstrophies, 10
      cloacal exstrophies, and two epispadias. The appendix and tapered ileum were used
      for the creation of a CCS in 11 and 15 patients, respectively. The median (range)
      age at creation of a CCS was 10.7 (4.4-17.4) years. At the time of CCS creation,
      21 patients underwent initial enterocystoplasty, four had repeat augmentations,
      and one had a CCS on a previously augmented bladder. Ileum (mean length 18 cm)
      was used in 24/25 augmentations and was selected owing to lack of redundant
      sigmoid in 52% of patients and intraoperative surgeon preference in the remaining
      cases. In one case of cloacal exstrophy, a hindgut remnant was used. In 24 (92%)
      cases, initial CCS resulted in complete continence of the catheterizable channel.
      After a median (range) of 2.5 (0.2-7.5) years' follow-up all patients were dry
      via intermittent catheterization. The CCS failed at postoperative months 6 and 21
      and required complete revision in two cases. CONCLUSIONS: Using a ST to provide a
      strong backing for a catheterizable channel is an excellent option when a channel
      must be placed in the ileum, hindgut, or in an area of augmentation where
      muscular backing is not available. The ST technique provides a reliably
      catheterizable tunnel, durable continence mechanism and a good success rate when
      creating a CCS in combination with a urinary diversion.

PMID- 22863148
TI  - Fruit and vegetable consumption and risk of aggressive and non-aggressive
      urothelial cell carcinomas in the European Prospective Investigation into Cancer
      and Nutrition.
AB  - BACKGROUND: Many epidemiological studies have examined fruit and vegetable
      consumption in relation to the risk of urothelial cell carcinoma (UCC) of the
      bladder, but results are inconsistent. The association between fruit and
      vegetable consumption and UCC risk may vary by bladder tumour aggressiveness.
      Therefore, we examined the relation between fruit and vegetable consumption and
      the risk of aggressive and non-aggressive UCC in the European Prospective
      Investigation into Cancer and Nutrition (EPIC). METHODS: After 8.9 years of
      follow-up, 947UCC were diagnosed among 468,656 EPIC participants. Of these, 421
      could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At
      recruitment, fruit and vegetable consumption was assessed by validated dietary
      questionnaires. Multivariable hazard ratios were estimated using Cox regression
      stratified by age, sex and center and adjusted for smoking status, duration and
      intensity of smoking, and energy intake. RESULTS: Total consumption of fruits and
      vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A
      25 g/day increase in leafy vegetables and grapes consumption was associated with
      a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95%confidence
      interval (CI) 0.78-1.00 and HR 0.87; 95%CI 0.77-0.98, respectively), while the
      intake of root vegetables was inversely associated with risk of aggressive UCC
      (HR 0.87; 95%CI 0.77-0.98). CONCLUSION: Our study did not confirm a protective
      effect of total fruit and/or vegetable consumption on aggressive or non
      aggressive UCC. High consumption of certain types of vegetables and of fruits may
      reduce the risk of aggressive or non-aggressive UCC; however chance findings
      cannot be excluded.

PMID- 22863150
TI  - Climate change impact assessment in Veneto and Friuli Plain groundwater. Part II:
      a spatially resolved regional risk assessment.
AB  - Climate change impact assessment on water resources has received high
      international attention over the last two decades, due to the observed global
      warming and its consequences at the global to local scale. In particular, climate
      related risks for groundwater and related ecosystems pose a great concern to
      scientists and water authorities involved in the protection of these valuable
      resources. The close link of global warming with water cycle alterations
      encourages research to deepen current knowledge on relationships between climate
      trends and status of water systems, and to develop predictive tools for their
      sustainable management, copying with key principles of EU water policy. Within
      the European project Life+ TRUST (Tool for Regional-scale assessment of
      groundwater Storage improvement in adaptation to climaTe change), a Regional Risk
      Assessment (RRA) methodology was developed in order to identify impacts from
      climate change on groundwater and associated ecosystems (e.g. surface waters,
      agricultural areas, natural environments) and to rank areas and receptors at risk
      in the high and middle Veneto and Friuli Plain (Italy). Based on an integrated
      analysis of impacts, vulnerability and risks linked to climate change at the
      regional scale, a RRA framework complying with the Sources-Pathway-Receptor
      Consequence (SPRC) approach was defined. Relevant impacts on groundwater and
      surface waters (i.e. groundwater level variations, changes in nitrate
      infiltration processes, changes in water availability for irrigation) were
      selected and analyzed through hazard scenario, exposure, susceptibility and risk
      assessment. The RRA methodology used hazard scenarios constructed through global
      and high resolution model simulations for the 2071-2100 period, according to IPCC
      A1B emission scenario in order to produce useful indications for future risk
      prioritization and to support the addressing of adaptation measures, primarily
      Managed Artificial Recharge (MAR) techniques. Relevant outcomes from the
      described RRA application highlighted that potential climate change impacts will
      occur with different extension and magnitude in the case study area.
      Particularly, qualitative and quantitative impacts on groundwater will occur with
      more severe consequences in the wettest and in the driest scenario
      (respectively). Moreover, such impacts will likely have little direct effects on
      related ecosystems - croplands, forests and natural environments - lying along
      the spring area (about 12% of croplands and 2% of natural environments at risk)
      while more severe consequences will indirectly occur on natural and anthropic
      systems through the reduction in quality and quantity of water availability for
      agricultural and other uses (about 80% of agricultural areas and 27% of
      groundwater bodies at risk).

PMID- 22863151
TI  - Thirty years of cornea cultivation: long-term experience in a single eye bank.
AB  - PURPOSE: To evaluate donor demographics, trends in donor tissue procurement and
      tissue storage over a long period. METHODS: A retrospective, longitudinal,
      descriptive analysis was undertaken of data from the Hamburg Eye Bank Data Base
      (HEB-DB) that had been collected between 1981 and 2010. Data on 54 parameters of
      cornea donors [including clinical history, age, death cause, gender and death-to
      explantation interval (DEI)] and of cultivated corneas (endothelial quality and
      development in culture, cultivation period, microbiological contamination) were
      retrieved. These data were analysed statistically, focusing on the historical
      development of the eye bank. RESULTS: At the time of retrieval (June 2010), the
      HEB-DB contained data on 10 943 corneas (5503 donors). Most donors were men (65%)
      and had died from cardiopulmonary (n = 801)/cerebral (n = 261) failure or as the
      result of a polytraumatic accident/suicide (n = 602). Within these years, donor
      age, DEI and storage time increased. The percentage of stored corneas suitable
      for transplantation displayed a variable but increasing trend; in 2007, almost
      75% of the stored corneas were transplanted. Between 1995 and June 2010, the
      median microbiological contamination rate was 5.3%. A change in the procurement
      procedure from enucleation to corneoscleral explantation in 2008 led to a briefly
      increased contamination rate. CONCLUSION:   Donor demographic data run parallel
      to the general demographic development. Our analysis indicates a dynamic
      development of the eye bank over the last 30 years and emphasizes the need for an
      active quality management in coping with the challenges of modern eye banking.

PMID- 22863152
TI  - Bayesian model selection validates a biokinetic model for zirconium processing in
      humans.
AB  - BACKGROUND: In radiation protection, biokinetic models for zirconium processing
      are of crucial importance in dose estimation and further risk analysis for humans
      exposed to this radioactive substance. They provide limiting values of
      detrimental effects and build the basis for applications in internal dosimetry,
      the prediction for radioactive zirconium retention in various organs as well as
      retrospective dosimetry. Multi-compartmental models are the tool of choice for
      simulating the processing of zirconium. Although easily interpretable,
      determining the exact compartment structure and interaction mechanisms is
      generally daunting. In the context of observing the dynamics of multiple
      compartments, Bayesian methods provide efficient tools for model inference and
      selection. RESULTS: We are the first to apply a Markov chain Monte Carlo approach
      to compute Bayes factors for the evaluation of two competing models for zirconium
      processing in the human body after ingestion. Based on in vivo measurements of
      human plasma and urine levels we were able to show that a recently published
      model is superior to the standard model of the International Commission on
      Radiological Protection. The Bayes factors were estimated by means of the
      numerically stable thermodynamic integration in combination with a recently
      developed copula-based Metropolis-Hastings sampler. CONCLUSIONS: In contrast to
      the standard model the novel model predicts lower accretion of zirconium in
      bones. This results in lower levels of noxious doses for exposed individuals.
      Moreover, the Bayesian approach allows for retrospective dose assessment,
      including credible intervals for the initially ingested zirconium, in a
      significantly more reliable fashion than previously possible. All methods
      presented here are readily applicable to many modeling tasks in systems biology.

PMID- 22863153
TI  - Non-cognitive characteristics predicting academic success among medical students
      in Sri Lanka.
AB  - BACKGROUND: To identify non-cognitive and socio-demographic characteristics
      determining academic success of Sri Lankan medical undergraduates. METHODS: A
      retrospective study among 90 recently graduated students of the Faculty of
      Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. Students were
      stratified into two equal groups; 'High-achievers' (honours degree at the final
      MBBS examination) and 'Low-achievers' (repeated one or more subjects at the same
      examination). A revised version of the Non-cognitive Questionnaire (NQ) with
      additional socio-demographic data was the study instrument. Academic performance
      indicator was performance at the final MBBS examinations. A binary logistic
      regression analysis was performed using the dichotomous variable 'Honours degree
      at final MBBS' as the dependant factor. RESULTS: Males were 56.7%. Mean age +/-
      SD was 26.4 +/- 0.9 years. 'High-achievers' were significantly younger than 'Low
      achievers'. Significant proportion of 'High-achievers' were from the Western
      province and selected to university from Colombo district. A significant majority
      of 'High-achievers' entered medical school from their first attempt at GCE A/L
      examination and obtained 'Distinctions' at the GCE A/L English subject. 'High
      achievers' demonstrated a significantly higher mean score for the following
      domains of NQ; Positive self-concept and confidence, realistic self-appraisal,
      leadership, preference of long range goals and academic familiarity.The binary
      logistic regression indicates that age, being selected to university from Colombo
      district, residency in Western province, entering university from GCE A/L first
      attempt, obtaining a 'Distinction' for GCE A/L English subject, higher number of
      patient-oriented case discussions, positive self-concept and confidence,
      leadership qualities, preference of long range goals and academic familiarity all
      significantly increased the odds of obtaining a Honours degree. CONCLUSION: A
      combined system incorporating both past academic performance and non-cognitive
      characteristics might help improve the selection process and early recognition of
      strugglers.

PMID- 22863154
TI  - Inter-arm difference in blood pressure may have serious research and clinical
      implications.

PMID- 22863155
TI  - Which is the endothelium-dependent "fair sex" in hypertension?

PMID- 22863156
TI  - Guideline adherence in cardiovascular risk assessment and analysis in 15,000
      hypertensive German patients in real life: results of the Prospective 3A
      Registry.
AB  - The benefit obtained from antihypertensive treatment is related more to overall
      cardiovascular risk reduction than to blood pressure levels. Accurate
      implementation of cardiovascular diagnostics is a key step toward assessment of
      cardiovascular risk. In the 3A Registry study, data about patient history,
      concomitant diseases, diagnostic procedures, and medications were prospectively
      collected. A total of 14,738 patients recruited by 899 physicians in 2008 and
      2009 were analyzed. Assessment of cardiovascular risk factors and subclinical end
      organ damage (SOD) showed broad differences in the implementation of European
      Society of Hypertension/European Society of Cardiology recommendations.
      Electrocardiograms were available in 59% of patients, cholesterol in 71.4%, and
      glucose in 69.7%. Almost all patients (99.6%) had creatinine measurements
      performed and microalbuminuria was measured in 8.5%. Metabolic syndrome (MS) had
      been evaluated in 59.7%. Implementation of diagnostic guidelines was highest in
      hypertensive patients with diabetes, followed by patients with known
      cardiovascular disease and established chronic renal insufficiency. For
      hypertensive patients without known comorbidities, the authors estimated that up
      to 29% had missed SOD (detection rate <50%) and 13% missed MS due to incomplete
      assessment of risk factors. This large registry study shows that assessment for
      cardiovascular risk factors and SOD is incomplete. Major efforts are required to
      improve comprehensive hypertension management as recommended by current
      guidelines.

PMID- 22863157
TI  - Components of the metabolic syndrome differ between young and old adults in the
      US population.
AB  - Prevalence of the metabolic syndrome (MetS) is high in the United States and is
      associated with increased risk of cardiovascular disease and diabetes. The
      authors examined whether the prevalence of the MetS and its components differs
      across age groups. Data were analyzed from 4 National Health and Nutrition
      Examination Surveys between the years 1999 and 2006. Prevalence of MetS as
      defined by the Third Report of the Adult Treatment Panel criteria and prevalence
      of associated cardiac risk factors were determined in 41,474 participants aged 18
      years and older without a history of cardiovascular disease (CVD). All estimates
      were weighted. Prevalence of MetS among asymptomatic adults without CVD was 20.5%
      and remained stable for the total population during survey periods. Prevalence of
      MetS increased with age: 6.6% in young adults (age 18-29 years) and 34.6% in
      older adults (70 and older). Components of MetS differed between young and old
      adults. Young adults had lower levels of high-density lipoprotein cholesterol,
      less glucose intolerance, and less hypertension. This study provides an estimate
      of MetS prevalence in asymptomatic adults in the United States during an 8-year
      period revealing that MetS affects a large number of Americans. Components of
      MetS differ between young and old adults and may have important implications in
      their clinical management.

PMID- 22863158
TI  - Can metabolic syndrome presence predict carotid intima-media thickness?
AB  - The aim of this investigation was to analyze metabolic syndrome (MS) impact on
      carotid intima-media thickness (cIMT). Prospective study of 300 patients with
      suspected coronary artery disease admitted for an elective coronary angiography
      were evaluated. Patients with previously known cardiac disease were excluded. In
      the population, 23.0% were diabetics and 40.5% had MS (but no diabetes). cIMT was
      not significantly different in patients with MS, but was significantly higher in
      diabetic patients compared with MS and control patients. Independent predictors
      of cIMT were age, male gender, insulin, and high-density lipoprotein (HDL)
      cholesterol (the last one with an inverse association). In patients without MS,
      only age and HDL cholesterol were associated. In patients with MS, independent
      predictors were age, male gender, and glucose, and abdominal obesity showed an
      inverse relationship. In patients with stable angina, MS is not an independent
      predictor of cIMT. Nonmodifiable variables (age and gender) are the most
      important determinants of cIMT, as well as blood glucose, in MS patients.
      Abdominal obesity was protective. J Clin Hypertens (Greenwich). 2012;00:00-00.
      (c)2012 Wiley Periodicals, Inc.

PMID- 22863159
TI  - Aliskiren alone or in combination with hydrochlorothiazide in Hispanic/Latino
      patients with systolic blood pressure 160 mm Hg to <180 mm Hg (Aliskiren Alone or
      in Combination with Hydrochlorothiazide in Patients with Stage 2 Hypertension to
      Provide Quick Intensive Control of Blood Pressure [ACQUIRE] substudy).
AB  - In a prespecified subgroup analysis of a 12-week multinational, randomized,
      double-blind, parallel-group trial, self-identified Hispanic/Latino adult men and
      women with systolic blood pressure 160 mm Hg to 179 mm Hg received combination
      aliskiren/hydrochlorothiazide (HCT) 150/12.5 mg or aliskiren 150 mg (force
      titrated to 300/25 mg and 300 mg, respectively, at week 1). At week 12,
      combination aliskiren/HCT provided greater reduction in mean sitting systolic
      blood pressure from baseline, the primary efficacy variable, compared with
      aliskiren monotherapy (-32.6 mm Hg vs -19.6 mm Hg; P<.0001). Differences in mean
      sitting diastolic blood pressure reductions followed a similar pattern (-13.5 mm
      Hg vs -7.1 mm Hg; P<.0001). Notable blood pressure reductions were evident at
      week 1 in both treatment groups, with near-maximal effects reached by week 8.
      Results were consistent regardless of country of residence. Both treatments were
      well tolerated. Aliskiren alone or in combination with HCT is safe and effective
      in Hispanic/Latino patients with stage 2 hypertension. Combination aliskiren/HCT
      produced greater blood pressure reductions than aliskiren monotherapy.

PMID- 22863160
TI  - Effects of aliskiren-based therapy on ambulatory blood pressure profile, central
      hemodynamics, and arterial stiffness in nondiabetic mild to moderate hypertensive
      patients.
AB  - Aliskiren is a direct renin inhibitor that exerts its effect at the rate-limiting
      step of the renin-angiotensin system. This study was performed to examine the
      beneficial effects of aliskiren-based antihypertensive therapy on the ambulatory
      blood pressure (BP) profile, central hemodybamics, and arterial stiffness in
      untreated Japanese patients with mild to moderate hypertension. Twenty-one
      Japanese nondiabetic patients with untreated mild to moderate essential
      hypertension were initially given aliskiren once daily at 150 mg, and the dose
      was titrated up to 300 mg as needed. After 12 weeks of aliskiren-based therapy,
      the clinic, ambulatory, and central BP values as well as brachial-ankle pulse
      wave velocity (baPWV) were all significantly decreased compared with baseline
      (clinic systolic BP, 151 +/- 11 mm Hg vs 132 +/- 11 mm Hg; clinic diastolic BP,
      91 +/- 13 mm Hg vs 82 +/- 9 mm Hg; 24-hour systolic BP, 144 +/- 12 mm Hg vs 133
      +/- 11 mm Hg; 24-hour diastolic BP, 88 +/- 8 mm Hg vs 81 +/- 9 mm Hg; central BP,
      162 +/- 16 mm Hg vs 148 +/- 14 mm Hg; baPWV, 1625 +/- 245 cm/s vs 1495 +/- 199
      cm/s; P<.05). These results show that aliskiren, as a first-line regimen,
      improves the ambulatory BP profile and may have protective vascular effects in
      Japanese nondiabetic patients with untreated mild to moderate essential
      hypertension.

PMID- 22863161
TI  - Are sleep symptoms predictors of resistant hypertension in a population-based
      sample? Findings from the National Health and Nutritional Examination Survey.
AB  - The aim of this study was to test the association of self-reported sleep symptoms
      to those identified with severe hypertension in a nationally representative
      sample of adults. Self-reported and study-measured health and sleep
      characteristics were collected by the National Health and Nutrition Examination
      Survey (NHANES) from 2005 to 2008. Of 10,526 individuals with completed sleep
      surveys participating in the study, the authors identified 379 patients with
      severe hypertension defined as those treated with >= 3 antihypertensive
      medications including a diuretic; 110 of these had resistant hypertension (RHTN)
      despite therapy, while 269 were controlled for severe hypertension (CSHTN).
      Patients with RHTN were more likely to be married, less educated, smoke, and self
      report unsatisfactory health and diabetes when compared with patients with CSHTN.
      Multivariate analyses showed that poorly controlled diabetes (glycated hemoglobin
      >7%) was the strongest predictor of RHTN (odds ratio, 3.0; 95% confidence
      interval, 1.2-7.9). Unsatisfactory health (odds ratio, 1.7; 95% confidence
      interval, 1.7-2.7) was also associated with RHTN. Poorly controlled diabetes and
      self-reported unsatisfactory heath showed significant association with RHTN.
      Contrary to expectations, there was no significant association between self
      reported snoring/snorting and RHTN, when other factors were examined. The
      association between poorly controlled diabetes and RHTN warrants further emphasis
      on strict control of diabetes in these individuals.

PMID- 22863162
TI  - Prognostic impact of baseline low blood pressure in hypertensive patients with
      stable coronary artery disease of daily clinical practice.
AB  - The authors' aim was to investigate the prognostic value of first-visit systolic
      and diastolic blood pressure (SBP/DBP) in hypertensive patients with stable
      coronary artery disease (sCAD) in conditions of contemporary daily clinical
      practice. From February 1, 2000, to January 31, 2004, 690 consecutive
      hypertensive patients with sCAD (mean age 68 +/- 10 years, 65% male) were
      prospectively followed in the outpatient cardiology clinic for major events
      (acute coronary syndrome, revascularization, stroke, heart failure, or death) and
      associations with baseline SBP/DBP were investigated. At first visit, median
      SBP/SDP were 130/75 mm Hg (interquartile range, 25-75; 120-140/70-80 mm Hg).
      After 25 months of follow-up (median), 19 patients died (2.8%); 10 from
      cardiovascular causes (1.5%), 87 patients experienced a coronary event (13%), and
      130 patients (19%) a major event. After adjusting for baseline variables, DBP <75
      mm Hg or SBP <130 mm Hg resulted in independent predictors of major events
      (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.07-2.16, P=.02; HR,
      1.68; 95% CI, 1.18-2.40, P=.004, respectively), coronary events (HR, 1.78; 95%
      CI, 1.15-2.75, P=.009; HR, 1.84; 95% CI, 1.20-2.83, P=.005, respectively), and
      cardiovascular mortality (HR, 7.02; 95% CI, 1.26-39.04, P=.03; HR, 9.26; 95% CI,
      1.33-64.32, P=.02, respectively). In this study, a low first-visit SBP or DBP was
      associated with an adverse prognosis in hypertensive patients with sCAD of
      contemporary daily clinical practice.

PMID- 22863163
TI  - Cerebrovascular consequences of pseudohyperaldosteronism.
AB  - The study of mechanistically defined forms of hypertension may provide insight
      into the relationship between hypertension and stroke. The author retrospectively
      studied a cohort of 23 individuals with pseudohyperaldosteronism (PHA), a
      condition associated with pathologic activation of the distal nephron epithelial
      sodium channel but low renin and aldosterone levels. During a median follow-up of
      11 years (range: 1-30), 4 of 23 (17.4%) patients had a cerebrovascular event
      recorded. Intracranial hemorrhage was not observed in any patient.
      Cerebrovascular events tended to occur in older patients, minorities, and
      patients with a later diagnosis of PHA and additional vascular risk factors. In
      addition to strict blood pressure control, patients with PHA should have early
      evaluation and treatment of other vascular risk factors to reduce the risk of
      stroke.

PMID- 22863164
TI  - Effects of sauna alone and postexercise sauna baths on blood pressure and
      hemodynamic variables in patients with untreated hypertension.
AB  - The effects of sauna alone vs exercise and sauna on ambulatory blood pressure
      monitoring and central hemodynamic variables were measured in 16 patients with
      untreated hypertension assigned to a control period, sauna, or exercise and
      sauna. Exercise and sauna had positive effects on 24-hour systolic and mean blood
      pressure in patients with untreated hypertension. Exercise and sauna and sauna
      alone reduce total vascular resistance, with positive effects lasting up to 120
      minutes after heat exposure.

PMID- 22863165
TI  - Metabolic syndrome in South Asians.
AB  - Metabolic syndrome (MS) is a cluster of multiple cardio-metabolic risk factors in
      the same individual. People with MS are at high risk for the development of
      cardiovascular disease (CVD), chronic kidney disease (CKD), and cerebrovascular
      disease (CeVD). The excessive presence of MS in South Asians is likely
      responsible for significant morbidity in this population. This review discusses
      the scope of MS in South Asians and measures to combat its effects by preventive
      and therapeutic measures.

PMID- 22863166
TI  - Primary aldosteronism in a patient who exhibited heart failure.

PMID- 22863167
TI  - Successful preoperative treatment of a patient with resistant hypertension who
      had percutaneous renal denervation therapy before bariatric surgery.

PMID- 22863168
TI  - Reynolds risk score as a risk assessment tool for cardiovascular disease after 10
      years: its strong relationship with blood pressure.

PMID- 22863169
TI  - Diet-induced obesity in ad libitum-fed mice: food texture overrides the effect of
      macronutrient composition.
AB  - Diet-induced obesity in mice can be achieved through the use of diets with
      different macronutrient compositions and textures. We aimed at determining the
      contribution of macronutrient composition to obesity development and associated
      pathophysiological changes in mice. C57BL/6N mice were offered a control, a high
      fat or a Western-style diet, either as pellet (H for hard) or with identical
      composition in powder form (S for soft), resulting in C-S, C-H, HF-H, HF-S, W-H
      and W-S groups, respectively. Body fat distribution, expression levels of
      selected target genes in adipose tissues, clinical chemistry and hormone
      concentration in the blood, as well as liver TAG content were measured. The most
      striking finding was that all mice fed the different powder diets developed
      obesity with similar weight gain, whereas among the mice fed the pellet diets,
      only those given the HF and W diets became obese. This allowed us to separate
      diet-specific effects from obesity-mediated effects. Irrespective of the food
      texture, the W diet induced a more severe hepatosteatosis and higher activities
      of serum transaminases compared with the two other diets. Adipose tissue gene
      expression analysis revealed that leptin and adiponectin levels were not affected
      by the dietary composition per se, whereas uncoupling protein 1 and 11beta
      hydroxysteroid dehydrogenase type 1 levels were decreased by both dietary
      composition and changes in body weight. In conclusion, diets differing in
      macronutrient composition elicit specific pathophysiological changes,
      independently of changes in body weight. A diet high in both fat and sugars seems
      to be more deleterious for the liver than a HF diet.

PMID- 22863170
TI  - Spatial synchrony of malaria outbreaks in a highland region of Ethiopia.
AB  - To understand the drivers and consequences of malaria in epidemic-prone regions,
      it is important to know whether epidemics emerge independently in different areas
      as a consequence of local contingencies, or whether they are synchronised across
      larger regions as a result of climatic fluctuations and other broad-scale
      drivers. To address this question, we collected historical malaria surveillance
      data for the Amhara region of Ethiopia and analysed them to assess the
      consistency of various indicators of malaria risk and determine the dominant
      spatial and temporal patterns of malaria within the region. We collected data
      from a total of 49 districts from 1999-2010. Data availability was better for
      more recent years and more data were available for clinically diagnosed
      outpatient malaria cases than confirmed malaria cases. Temporal patterns of
      outpatient malaria case counts were correlated with the proportion of outpatients
      diagnosed with malaria and confirmed malaria case counts. The proportion of
      outpatients diagnosed with malaria was spatially clustered, and these cluster
      locations were generally consistent from year to year. Outpatient malaria cases
      exhibited spatial synchrony at distances up to 300 km, supporting the hypothesis
      that regional climatic variability is an important driver of epidemics. Our
      results suggest that decomposing malaria risk into separate spatial and temporal
      components may be an effective strategy for modelling and forecasting malaria
      risk across large areas. They also emphasise both the value and limitations of
      working with historical surveillance datasets and highlight the importance of
      enhancing existing surveillance efforts.

PMID- 22863171
TI  - Controlled synthesis of bilayer graphene on nickel.
AB  - We report a uniform and low-defect synthesis of bilayer graphene on evaporated
      polycrystalline nickel films. We used atmospheric pressure chemical vapor
      deposition with ultra-fast substrate cooling after exposure to methane at 1,000
      degrees C. The optimized process parameters, i.e., growth time, annealing profile
      and flow rates of various gases, are reported. By using Raman spectroscopy
      mapping, the ratio of 2D to G peak intensities (I2D/IG) is in the range of 0.9 to
      1.6 over 96% of the 200 MUm * 200 MUm area. Moreover, the average ratio of D to G
      peak intensities (ID/IG) is about 0.1.

PMID- 22863172
TI  - Perinatal and early life factors associated with symptoms of depression in
      Brazilian children.
AB  - BACKGROUND: Few studies have been conducted on the association between perinatal
      and early life factors with childhood depression and results are conflicting. Our
      aim was to estimate the prevalence and perinatal and early life factors
      associated with symptoms of depression in children aged 7 to 11 years from two
      Brazilian birth cohorts. METHODS: The study was conducted on 1444 children whose
      data were collected at birth and at school age, in 1994 and 2004/2005 in Ribeirao
      Preto, where they were aged 10-11 years and in 1997/98 and 2005/06 in Sao Luis,
      where children were aged 7-9 years. Depressive symptoms were investigated with
      the Child Depression Inventory(CDI), categorized as yes (score >= 20) and no
      (score < 20). Adjusted and non-adjusted prevalence ratios (PR) were estimated by
      Poisson regression with robust estimation of the standard errors. RESULTS: The
      prevalence of depressive symptoms was 3.9% (95%CI = 2.5-5.4) in Ribeirao Preto
      and 13.7% (95%CI = 11.0-16.4) in Sao Luis. In the adjusted analysis, in Ribeirao
      Preto, low birth weight (PR = 3.98; 95%CI = 1.72-9.23), skilled and semi-skilled
      manual occupation (PR = 5.30; 95%CI = 1.14-24.76) and unskilled manual occupation
      and unemployment (PR = 6.65; 95%CI = 1.16-38.03) of the household head were risk
      factors for depressive symptoms. In Sao Luis, maternal schooling of 0-4 years (PR
      = 2.39; 95%CI = 1.31-4.34) and of 5 to 8 years (PR = 1.80; 95%CI = 1.08-3.01),
      and paternal age <20 years (PR = 1.92; 95%CI = 1.02-3.61), were independent risk
      factors for depressive symptoms. CONCLUSIONS: The prevalence of depressive
      symptoms was much higher in the less developed city, Sao Luis, than in the more
      developed city, Ribeirao Preto, and than those reported in several international
      studies. Low socioeconomic level was associated with depressive symptoms in both
      cohorts. Low paternal age was a risk factor for depressive symptoms in the less
      developed city, Sao Luis, whereas low birth weight was a risk factor for
      depressive symptoms in the more developed city, Ribeirao Preto.

PMID- 22863173
TI  - Thrombolysis in ischemic strokes with no arterial occlusion.
AB  - RATIONALE: Twelve million people develop ischemic stroke each year world over and
      30-40% of them do not have arterial occlusions at presentation. Trials conducted
      to study the efficacy of thrombolytic drug reported better outcome with use of
      thrombolytic drug but none studied the subtypes of ischemic strokes specifically
      and adequately. The subgroups of patients with no arterial occlusion at
      presentation continue to receive thrombolytic therapy without proven benefit and
      with some risk. AIM: The aim of this article is to study whether intravenous
      thrombolysis with alteplase improves clinical outcome in ischemic stroke patients
      who do not have arterial occlusion at presentation. DESIGN: A retrospective
      medical record-based observational multicenter, multinational study. OUTCOMES:
      Primary outcome measure would be clinical outcome at three-months from stroke
      onset measured by modified Rankin Scale and National Institute of Health Stroke
      Scale. Secondary outcome measure will be frequency of intracerebral hemorrhage
      causing worsening of clinical deficit defined as increase in National Institute
      of Health Stroke Scale by >4.

PMID- 22863174
TI  - Left ventricular functional assessment in murine models of ischemic and dilated
      cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring
      erythropoietin therapy.
AB  - BACKGROUND: We performed an initial evaluation of non-invasive ECG-gated [18
      F]FDG-positron emission tomography (FDG-PET) for serial measurements of left
      ventricular volumes and function in murine models of dilated (DCM) and ischemic
      cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO)
      treatment on DCM mice in a preliminary FDG-PET therapy monitoring study. METHODS:
      Mice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas
      ICM was induced by ligation of the left anterior descending artery. LV volumes
      (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control
      mice were measured by FDG-PET and compared with reference standard results
      obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent
      monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and
      after 4 weeks of treatment, with EPO or saline. RESULTS: LV volumes and the LVEF
      as measured by FDG-PET correlated significantly with the MRI results. These
      correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF
      measurements were somewhat compromised by absence of FDG uptake in the area of
      infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG
      PET, with net bias such that LVEF measurements in both models of heart disease
      exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring
      study of DCM mice, we found a significant decrease of LVEF in the EPO group, but
      not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice
      significantly correlated with histological scores of fibrosis. CONCLUSIONS: LVEF
      estimated by ECG-gated FDG-PET significantly correlated with the reference
      standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for
      longitudinal monitoring of effects of EPO treatment in DCM mice.

PMID- 22863175
TI  - Usefulness of hyponatremia in the acute phase of ST-elevation myocardial
      infarction as a marker of severity.
AB  - Whether hyponatremia (sodium <135 mEq/L) in the acute phase of ST-segment
      elevation myocardial infarction is just a marker of "more ill" patients or
      decreased sodium concentration is able to exert a direct adverse effect on the
      cardiovascular system is still unknown. The aim of this study was to assess the
      prognostic impact, in the short and long terms, of admission hyponatremia in
      1,231 consecutive patients with ST-segment elevation myocardial infarctions all
      submitted to primary percutaneous coronary intervention. In this series, 286
      patients (23.2%) had sodium values <135 mEq/L. Patients with hyponatremia were
      older (p = 0.018) and more frequently had diabetes (p = 0.040). Anterior
      myocardial infarction was more frequent in patients with hyponatremia, who showed
      a higher incidence of 3-vessel coronary artery disease and advanced Killip class.
      Higher mortality rates were observed in patients with hyponatremia during
      intensive cardiac care unit stay and at follow-up. On multivariate regression
      analysis, admission sodium concentration was not independently related to early
      death, nor did it show any relations with long-term mortality on Cox regression
      analysis. In conclusion, the main findings of the present investigation are as
      follows: (1) hyponatremia is a common finding, being associated mainly with older
      age, diabetes, and advanced Killip class; (2) patients with hyponatremia had
      higher rates of in-hospital and long-term mortality; and (3) hyponatremia, also
      when assessed by means of the propensity score model, was not independently
      associated with increased risk for death in the short and long terms. These data
      therefore strongly suggest that the presence of hyponatremia in the acute phase
      of ST-segment elevation myocardial infarction should be considered a marker of
      more ill patients.

PMID- 22863176
TI  - Usefulness of serum brain natriuretic peptide to predict adverse events in
      patients with the Eisenmenger syndrome.
AB  - The aim of this study was to evaluate the prognostic value of brain natriuretic
      peptide (BNP) in outpatients with the Eisenmenger syndrome (ES). BNP is often
      elevated in patients with cyanotic congenital heart disease. The clinical utility
      of BNP in patients with cyanotic congenital heart disease and the ES has not been
      clearly delineated. Records of adults with ES who had undergone serum BNP
      measurement were reviewed. The primary end point was death or heart failure
      admission. Fifty-three patients were included, with 15 patients (28%) meeting the
      primary end point (death in 7, heart failure hospitalization in 8). Mean and
      median baseline BNP in patients meeting the primary end point were 322 +/- 346
      and 179 pg/ml, compared to 100 +/- 157 and 41 pg/ml in those not meeting the
      primary end point (p = 0.0029). A Cox proportional-hazards model using baseline
      BNP between the 2 groups yielded a hazard ratio of 1.84 (95% confidence interval
      [CI] 1.19 to 2.85, p = 0.006). The relative risk for baseline BNP level >140
      pg/ml was 4.62 (95% CI 1.80 to 11.3, p = 0.008). Patients who met the primary end
      point increased their BNP levels by 42.5 pg/ml per year (95% CI 12.09 to 72.95, p
      = 0.006) compared to 7.2 pg/ml per year (95% CI 2.01 to 12.47, p = 0.007) in
      patients who did not meet the primary end point. In conclusion, elevated BNP
      levels are predictive of death or heart failure admission in patients with the
      ES. A serum BNP level >140 pg/ml is a useful tool in identifying high-risk
      patients.

PMID- 22863177
TI  - Long-term outcome of patients with moderate and severe prosthetic aortic valve
      regurgitation after transcatheter aortic valve implantation.
AB  - Recently, moderate and severe postprocedure aortic regurgitations (ARs) have been
      identified as independent risk factors for short- and midterm mortality after
      transcatheter aortic valve implantation (TAVI). However, very few data exist on
      the long-term outcome of postprocedure AR. From 2008 to 2011, 198 consecutive
      patients with severe aortic stenosis successfully underwent TAVI with the
      CoreValve prosthesis (Medtronic CV, Minneapolis, Minnesota). After the procedure,
      patients were subdivided into groups depending on the presence of moderate/severe
      AR. The primary study end point was death from any cause after TAVI. The
      secondary end point was defined as cardiovascular death. In study patients (80 +/
      6 years old, logistic European System for Cardiac Operative Risk Evaluation 22
      +/- 16%, left ventricular ejection fraction 53 +/- 13%), moderate/severe AR
      occurred in 28 patients (14%). Despite similar baseline characteristics, patients
      with moderate/severe AR had higher 30-day and 1-year mortality rates than
      patients with none/mild AR (21% vs 6%, p = 0.019; 57% vs 16%, p <0.001,
      respectively). During a mean follow-up of 535 +/- 333 days, the primary end point
      was reached in 54 and the secondary end point in 33 patients. Moderate/severe AR
      was the strongest independent risk factor of all-cause-mortality (hazard ratio
      4.89, 95% confidence interval 2.78 to 8.56, p <0.001) and the strongest
      independent risk factor of cardiovascular mortality (hazard ratio 7.90, 95%
      confidence interval 3.95 to 15.81, p <0.001). In conclusion, moderate and severe
      postprocedure ARs are not uncommon complications after TAVI. Although long-term
      outcome of patients with none/mild AR is favorable, outcome of patients with
      moderate/severe AR is dismal.

PMID- 22863178
TI  - Diagnostic and prognostic value of subcutaneous tissue biopsy in patients with
      cardiac amyloidosis.
AB  - Cardiac involvement in systemic amyloidosis causes detrimental prognosis;
      therefore, early detection and classification are important to develop
      appropriate therapeutic strategies. Subcutaneous tissue biopsy is a useful
      screening procedure for systemic amyloidosis; however, its diagnostic and
      prognostic value in patients with cardiac amyloidosis remains elusive. Thus, we
      investigated the value of subcutaneous tissue biopsy in cardiac amyloidosis. In
      22 patients with cardiac amyloidosis, we retrospectively analyzed 14 consecutive
      patients with cardiac amyloidosis who underwent subcutaneous tissue biopsy.
      Amyloid deposition was observed in 11 patients (79%). Histopathologic analysis
      demonstrated that acquired monoclonal immunoglobulin light-chain amyloidosis
      could be predicted when the degree of amyloid deposition was greater in blood
      vessels than adipose tissue compared to senile systemic amyloidosis and familial
      amyloidosis (60% vs 0%, p = 0.03). During the follow-up period (median 297 days,
      range 3 to 761), 7 patients (5 with monoclonal immunoglobulin light-chain
      amyloidosis and 2 with senile systemic amyloidosis) died or were admitted to the
      hospital because of worsening heart failure. Of them, 6 patients (86%) were
      positive for amyloid deposition in blood vessels in subcutaneous tissue biopsy.
      Incidence of death and composite outcome including heart failure hospitalization
      and death was significantly higher in patients positive for amyloid deposition in
      blood vessels than in those without (p = 0.03, p = 0.006, respectively). These
      results suggest that amyloid subtype could be diagnosed by assessing the degree
      of amyloid deposition in blood vessels and adipose tissue in subcutaneous tissue
      biopsy samples from patients with cardiac amyloidosis. Amyloid deposition in
      blood vessels suggests poor prognosis of these patients.

PMID- 22863179
TI  - Enhanced performance and capacitance behavior of anode by rolling Fe3O4 into
      activated carbon in microbial fuel cells.
AB  - Fe(3)O(4) was added into the anode to improve the performance of microbial fuel
      cells (MFCs). Stainless steel mesh (SSM), activated carbon (AC) with SSM (AcM)
      and Fe(3)O(4) added AcM (AcFeM) anodes had been made and investigated by
      electrochemical measurements. The maximum power density of AcFeM anode (809 +/- 5
      mW/m(2)) is 22% higher than that of AcM (664 +/- 17 mW/m(2)), and 56 times higher
      than that of SSM anode (14 +/- 0.3 mW/m(2)). Tafel tests indicate that the anode
      modified by Fe(3)O(4) is kinetically more advantageous. It is demonstrated for
      the first time that the capacitance of anode increased after the addition of
      Fe(3)O(4). With 10 min of interruption, AcFeM exhibites a 41% higher cumulative
      charge of 3566 +/- 32 C/m(2) and a 32% higher net capacitance charge of 389 +/-
      18 C/m(2) than those of the AcM control (2529 +/- 22 and 294 +/- 30 C/m(2)),
      indicating that the improvement of anode performance can be also attributed to
      the enhancement of capacitance.

PMID- 22863180
TI  - Efficient dehydration of glucose to 5-hydroxymethylfurfural catalyzed by the
      ionic liquid,1-hydroxyethyl-3-methylimidazolium tetrafluoroborate.
AB  - The dehydration of fructose or glucose to 5-hydroxymethylfurfural (5-HMF) using
      room temperature ionic liquids (ILs) as a solvent is a promising method for
      producing liquid fuels from renewable resources. The IL, 1-hydroxyethyl-3
      methylimidazolium tetrafluoroborate ([C(2)OHMIM]BF(4)), was used a catalyst
      rather than as a solvent-in the conversion of fructose or glucose to 5-HMF. With
      glucose, the yield of 5-HMF reached as high as 67.3% after 1h at 180 degrees C in
      dimethylsulfoxide (DMSO) as solvent. The catalyst was separated from the reaction
      mixture by distilling solvent and reused six times without loss of activity.
      Furthermore, a kinetic analysis was carried out to illustrate the formation of 5
      HMF, and the values of the activation energy and the pre-exponential factor for
      the reaction were 55.77 kJ mol(-1) and 1.6 * 10(4)min(-1) respectively.

PMID- 22863182
TI  - Mortality and loss to follow-up among tuberculosis and HIV co-infected patients
      in rural southwestern Uganda.
AB  - BACKGROUND: We describe the presentation and outcome of care among patients with
      tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection from a
      prospective observational cohort in Uganda. METHODS: We analysed basic
      demographics, CD4+ counts, time of initiating antiretroviral  therapy (ART),
      clinical and haematological parameters and outcome of care of 386 patients
      enrolled between February 2007 and March 2010. RESULTS: At presentation, 56.7% of
      the patients were sputum-positive, 89.9% had new TB infection, 62.7% had wasting,
      78.7% were anaemic, 72.1% had a CD4+  count of <200 cells/mm(3), 20.2% had
      pneumonia, 50.3% had oral thrush and 1.3% had Kaposi's sarcoma. Patients
      developing TB within 3 months of starting ART were less likely to have wasting,
      to be anaemic or to have a CD4+ count of <100 cells/mm(3). The cure, default  and
      death rates were respectively 54.3%, 24% and 16%. At 8 months, 53 (13.7%) were
      confirmed dead, 119 (30.8%) were lost to follow-up, 28 (7.3%) were transferred
      out and 1 (0.3%) had treatment failure. Mortality and loss to follow-up were
      associated with failure to start ART and having a CD4+  count of <200
      cells/mm(3). CONCLUSION: In Uganda, TB-HIV patients present with severe immune
      suppression and are at increased risk of death and loss to follow-up,
      particularly those not on ART. There is need for early identification and
      improved follow-up of TB-HIV co-infected  patients.

PMID- 22863181
TI  - Molecular diagnosis of putative Stargardt Disease probands by exome sequencing.
AB  - BACKGROUND: The commonest genetic form of juvenile or early adult onset macular
      degeneration is Stargardt Disease (STGD) caused by recessive mutations in the
      gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but
      non-trivial amount of locus heterogeneity currently impede conclusive molecular
      diagnosis in a significant proportion of cases. METHODS: We performed whole exome
      sequencing (WES) of nine putative Stargardt Disease probands and searched for
      potentially disease-causing genetic variants in previously identified retinal or
      macular dystrophy genes. Follow-up dideoxy sequencing was performed for
      confirmation and to screen for mutations in an additional set of affected
      individuals lacking a definitive molecular diagnosis. RESULTS: Whole exome
      sequencing revealed seven likely disease-causing variants across four genes,
      providing a confident genetic diagnosis in six previously uncharacterized
      participants. We identified four previously missed mutations in ABCA4 across
      three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1
      were also identified. CONCLUSIONS: Our findings highlight the enormous potential
      of whole exome sequencing in Stargardt Disease molecular diagnosis and research.
      WES adequately assayed all coding sequences and canonical splice sites of ABCA4
      in this study. Additionally, WES enables the identification of disease-related
      alleles in other genes. This work highlights the importance of collecting
      parental genetic material for WES testing as the current knowledge of human
      genome variation limits the determination of causality between identified
      variants and disease. While larger sample sizes are required to establish the
      precision and accuracy of this type of testing, this study supports WES for
      inherited early onset macular degeneration disorders as an alternative to
      standard mutation screening techniques.

PMID- 22863183
TI  - Synthesis and biological evaluation of novel benzimidazole derivatives and their
      binding behavior with bovine serum albumin.
AB  - A series of novel benzimidazole derivatives were synthesized and characterized by
      (1)H NMR, (13)C NMR, MS, IR and HRMS spectra. All the new compounds were screened
      for their antimicrobial activities in vitro by two-fold serial dilution
      technique. Bioactive assay manifested that the bis-benzimidazole derivative 11d
      and its hydrochloride 13b exhibited remarkable antimicrobial activities, which
      were comparable or even better than the reference drugs Norfloxacin, Chloromycin
      and Fluconazole. The interaction evaluation of compound 11d with bovine serum
      albumin (BSA) by Fluorescence and UV-vis absorption spectroscopic method showed
      that BSA could generate fluorescent quenching under approximately human
      physiological conditions by the prepared benzimidazole compound 11d as result of
      the formation of ground-state compound 11d-BSA complex. The thermodynamic
      parameters indicated that the hydrogen bonds and van der Waals forces played
      major roles in the strong association of benzimidazole 11d and BSA.

PMID- 22863184
TI  - Use and functioning of the affected limb in children with unilateral congenital
      below-elbow deficiency during infancy and preschool age: a longitudinal
      observational multiple case study.
AB  - BACKGROUND: Children with unilateral congenital below elbow deficiency (UCBED)
      lack a part of an arm, thereby lacking a part of the typical hand function.
      Little is known on the performance of daily activities in very young children
      with UCBED, usage of their affected arm with or without prosthesis during play,
      and neurological condition. AIM: To explore daily activities, the use of the
      affected limb with or without prosthesis and neurological condition over time in
      young children with UCBED. DESIGN: A longitudinal observational multiple case
      study. METHODS: Four children with UCBED were assessed (first assessment at 3
      16months) every 6-8months (follow-up 13-49months) with a video-recorded,
      standardized play session and a neurological examination. Yearly, functioning in
      daily activities was evaluated using the Pediatric Evaluation of Disability
      Inventory - Dutch Version (PEDI-NL). Play behaviour was assessed with and without
      prosthesis, where applicable (n=2). Video-analysis focused on achievement,
      exploration, variation and adaptability of the affected limb. Behavioural changes
      over time were plotted and analysed visually. RESULTS: Over time, children with
      UCBED showed efficient usage of their affected arm during spontaneous play.
      Prosthesis use seemed to be associated with reduced manipulation, exploration,
      variation and adaptation. Three children showed minor neurological dysfunction.
      Functioning in daily activities was comparable to a norm population. CONCLUSION:
      The short limb of children with UCBED is used as an exploratory, manipulatory and
      fixating tool from the beginning of infancy. Its value seems to be reflected in
      these children's normal functioning in daily life. Prosthetic use may lead to
      less effective performance.

PMID- 22863185
TI  - Dual effect of prostaglandins on isolated intraocular porcine ciliary arteries.
AB  - PURPOSE: Prostaglandin analogues are used to reduce the intraocular pressure
      (IOP) in glaucoma, but also affect the tone of the arteries supplying the ciliary
      body. Previously, the effect of prostaglandins has been studied on the
      extraocular ciliary arteries, whereas the effect on intraocular ciliary arteries
      has not been studied in detail. METHODS: Intraocular long posterior porcine
      ciliary arteries were isolated and mounted in a myograph system for isometric
      tension recording, and the effects of PGF2alpha , the prostaglandin analogue
      latanoprost, PGD2 , PGE2 , PGI2 and the thromboxane analogue U46619 were studied
      in the presence and absence of selective receptor antagonists. RESULTS: The
      prostaglandins PGD2 and PGE2 induced relaxation at low concentrations (10(-9) - 3
      * 10(-7) m), which could be inhibited by blocking either the DP or the EP4
      receptor, whereas PGD2 , PGE2 , PGF2alpha , latanoprost and U46619 induced
      contraction at high concentrations (10(-6) - 10(-5) m), which could be inhibited
      by blocking the TP receptor. Additionally, blocking of the FP receptor induced a
      right-shift of latanoprost-induced contraction. CONCLUSIONS: Prostaglandins with
      affinity to DP1 and EP4 receptors induce relaxation at low concentrations, and
      prostaglandins with affinity to TP and FP receptors induce contraction at high
      concentrations of intraocular porcine ciliary vessels in vitro. The findings may
      contribute to understanding the regulation of blood flow to the ciliary body.

PMID- 22863186
TI  - Biotransformation of perfumery terpenoids, (-)-ambrox(r) by a fungal culture
      Macrophomina phaseolina and a plant cell suspension culture of Peganum harmala.
AB  - BACKGROUND: Biotransformation offers chemo enzymatic system to modify the
      compounds into their novel analogues which are difficult to synthesize by
      chemical methods. This paper describes the biotransformational studies of ambrox,
      one of the most important components of natural Ambergris (wale sperm) with
      fungal and plant cell culture. RESULTS: Biotransformation of (-)-ambrox (1) with
      a fungal cell culture of Macrophomina phaseolina and a plant cell suspension
      cultures of Peganum harmala yielded oxygenated products, 3beta-hydroxyambrox (2),
      6beta-hydroxyambrox (3), 1alpha-hydroxy-3oxoambrox (4), 1alpha,3beta
      dihydroxyambrox (5), 13,14,15,16-tetranorlabdane-3-oxo-8,12-diol (6), 3-oxoambrox
      (7), 2alpha-hydroxyambrox (8), 3beta-hydroxysclareolide (9), and 2alpha,3beta
      dihydroxyambrox (10). Metabolite 4 was found to be new compound. These
      metabolites were structurally characterized on the basis of spectroscopic
      studies. CONCLUSION: Nine oxygenated metabolites of (-)-ambrox (1) were obtained
      from Macrophomina phaseolina and Peganum harmala. Enzymatic system of screened
      organisms introduced hydroxyl and keto functionalities at various positions of
      compound 1 in a stereo- and regio-controlled manner.

PMID- 22863187
TI  - Transcriptome profiling of resistant and susceptible Cavendish banana roots
      following inoculation with Fusarium oxysporum f. sp. cubense tropical race 4.
AB  - BACKGROUND: Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f.
      sp. cubense tropical race 4 (Foc TR4), is considered the most lethal disease of
      Cavendish bananas in the world. The disease can be managed in the field by
      planting resistant Cavendish plants generated by somaclonal variation. However,
      little information is available on the genetic basis of plant resistance to Foc
      TR4. To a better understand the defense response of resistant banana plants to
      the Fusarium wilt pathogen, the transcriptome profiles in roots of resistant and
      susceptible Cavendish banana challenged with Foc TR4 were compared. RESULTS: RNA
      seq analysis generated more than 103 million 90-bp clean pair end (PE) reads,
      which were assembled into 88,161 unigenes (mean size = 554 bp). Based on sequence
      similarity searches, 61,706 (69.99%) genes were identified, among which 21,273
      and 50,410 unigenes were assigned to gene ontology (GO) categories and clusters
      of orthologous groups (COG), respectively. Searches in the Kyoto Encyclopedia of
      Genes and Genomes Pathway database (KEGG) mapped 33,243 (37.71%) unigenes to 119
      KEGG pathways. A total of 5,008 genes were assigned to plant-pathogen
      interactions, including disease defense and signal transduction. Digital gene
      expression (DGE) analysis revealed large differences in the transcriptome
      profiles of the Foc TR4-resistant somaclonal variant and its susceptible wild
      type. Expression patterns of genes involved in pathogen-associated molecular
      pattern (PAMP) recognition, activation of effector-triggered immunity (ETI), ion
      influx, and biosynthesis of hormones as well as pathogenesis-related (PR) genes,
      transcription factors, signaling/regulatory genes, cell wall modification genes
      and genes with other functions were analyzed and compared. The results indicated
      that basal defense mechanisms are involved in the recognition of PAMPs, and that
      high levels of defense-related transcripts may contribute to Foc TR4 resistance
      in banana. CONCLUSIONS: This study generated a substantial amount of banana
      transcript sequences and compared the defense responses against Foc TR4 between
      resistant and susceptible Cavendish bananas. The results contribute to the
      identification of candidate genes related to plant resistance in a non-model
      organism, banana, and help to improve the current understanding of host-pathogen
      interactions.

PMID- 22863188
TI  - A qualitative study on caretakers' perceived need of bed-nets after reduced
      malaria transmission in Zanzibar, Tanzania.
AB  - BACKGROUND: The elimination of malaria in Zanzibar is highly dependent on
      sustained effective coverage of bed-nets to avoid malaria resurgence. The Health
      Belief Model (HBM) framework was used to explore the perceptions of malaria and
      bed-net use after a noticeable reduction in malaria incidence. METHODS: Nineteen
      in-depth interviews were conducted with female and male caretakers of children
      under five in North A district, Zanzibar. Deductive content analysis was used to
      identify meaning units that were condensed, coded and assigned to pre-determined
      elements of the HBM. RESULTS: Awareness of malaria among caretakers was high but
      the illness was now seen as easily curable and uncommon. In addition to the
      perceived advantage of providing protection against malaria, bed-nets were also
      thought to be useful for avoiding mosquito nuisance, especially during the rainy
      season when the malaria and mosquito burden is high. The discomfort of sleeping
      under a net during the hot season was the main barrier that interrupted
      consistent bed-net usage. The main cue to using a bed-net was high mosquito
      density, and children were prioritized when it came to bed-net usage. Caretakers
      had high perceived self-efficacy and did not find it difficult to use bed-nets.
      Indoor Residual Spraying (IRS), which was recognized as an additional means of
      mosquito prevention, was not identified as an alternative for bed-nets. A barrier
      to net ownership was the increasingly high cost of bed-nets. CONCLUSIONS: Despite
      the reduction in malaria incidence and the resulting low malaria risk perceptions
      among caretakers, the benefit of bed-nets as the most proficient protection
      against mosquito bites upholds their use. This, in combination with the perceived
      high self-efficacy of caretakers, supports bed-net usage, while seasonality
      interrupts consistent use. High effective coverage of bed-nets could be further
      improved by reinforcing the benefits of bed-nets, addressing the seasonal heat
      barrier by using nets with larger mesh sizes and ensuring high bed-net ownership
      rates through sustainable and affordable delivery mechanisms.

PMID- 22863189
TI  - Exome sequencing followed by large-scale genotyping fails to identify single rare
      variants of large effect in idiopathic generalized epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) is a complex disease with high
      heritability, but little is known about its genetic architecture. Rare copy
      number variants have been found to explain nearly 3% of individuals with IGE;
      however, it remains unclear whether variants with moderate effect size and
      frequencies below what are reliably detected with genome-wide association studies
      contribute significantly to disease risk. In this study, we compare the exome
      sequences of 118 individuals with IGE and 242 controls of European ancestry by
      using next-generation sequencing. The exome-sequenced epilepsy cases include
      study subjects with two forms of IGE, including juvenile myoclonic epilepsy (n =
      93) and absence epilepsy (n = 25). However, our discovery strategy did not assume
      common genetic control between the subtypes of IGE considered. In the sequence
      data, as expected, no variants were significantly associated with the IGE
      phenotype or more specific IGE diagnoses. We then selected 3,897 candidate
      epilepsy-susceptibility variants from the sequence data and genotyped them in a
      larger set of 878 individuals with IGE and 1,830 controls. Again, no variant
      achieved statistical significance. However, 1,935 variants were observed
      exclusively in cases either as heterozygous or homozygous genotypes. It is likely
      that this set of variants includes real risk factors. The lack of significant
      association evidence of single variants with disease in this two-stage approach
      emphasizes the high genetic heterogeneity of epilepsy disorders, suggests that
      the impact of any individual single-nucleotide variant in this disease is small,
      and indicates that gene-based approaches might be more successful for future
      sequencing studies of epilepsy predisposition.

PMID- 22863190
TI  - A single recurrent mutation in the 5'-UTR of IFITM5 causes osteogenesis
      imperfecta type V.
AB  - Osteogenesis imperfecta (OI) is a heterogenous group of genetic disorders of bone
      fragility. OI type V is an autosomal-dominant disease characterized by
      calcification of the forearm interosseous membrane, radial head dislocation, a
      subphyseal metaphyseal radiodense line, and hyperplastic callus formation; the
      causative mutation involved in this disease has not been discovered yet. Using
      linkage analysis in a four-generation family and whole-exome sequencing, we
      identified a heterozygous mutation of c.-14C>T in the 5'-untranslated region of a
      gene encoding interferon-induced transmembrane protein 5 (IFITM5). It completely
      cosegregated with the disease in three families and occurred de novo in five
      simplex individuals. Transfection of wild-type and mutant IFITM5 constructs
      revealed that the mutation added five amino acids (Met-Ala-Leu-Glu-Pro) to the N
      terminus of IFITM5. Given that IFITM5 expression and protein localization is
      restricted to the skeletal tissue and IFITM5 involvement in bone formation, we
      conclude that this recurrent mutation would have a specific effect on IFITM5
      function and thus cause OI type V.

PMID- 22863191
TI  - Exome sequencing followed by large-scale genotyping suggests a limited role for
      moderately rare risk factors of strong effect in schizophrenia.
AB  - Schizophrenia is a severe psychiatric disorder with strong heritability and
      marked heterogeneity in symptoms, course, and treatment response. There is strong
      interest in identifying genetic risk factors that can help to elucidate the
      pathophysiology and that might result in the development of improved treatments.
      Linkage and genome-wide association studies (GWASs) suggest that the genetic
      basis of schizophrenia is heterogeneous. However, it remains unclear whether the
      underlying genetic variants are mostly moderately rare and can be identified by
      the genotyping of variants observed in sequenced cases in large follow-up cohorts
      or whether they will typically be much rarer and therefore more effectively
      identified by gene-based methods that seek to combine candidate variants. Here,
      we consider 166 persons who have schizophrenia or schizoaffective disorder and
      who have had either their genomes or their exomes sequenced to high coverage.
      From these data, we selected 5,155 variants that were further evaluated in an
      independent cohort of 2,617 cases and 1,800 controls. No single variant showed a
      study-wide significant association in the initial or follow-up cohorts. However,
      we identified a number of case-specific variants, some of which might be real
      risk factors for schizophrenia, and these can be readily interrogated in other
      data sets. Our results indicate that schizophrenia risk is unlikely to be
      predominantly influenced by variants just outside the range detectable by GWASs.
      Rather, multiple rarer genetic variants must contribute substantially to the
      predisposition to schizophrenia, suggesting that both very large sample sizes and
      gene-based association tests will be required for securely identifying genetic
      risk factors.

PMID- 22863192
TI  - Rare de novo germline copy-number variation in testicular cancer.
AB  - Although heritable factors are an important determinant of risk of early-onset
      cancer, the majority of these malignancies appear to occur sporadically without
      identifiable risk factors. Germline de novo copy-number variations (CNVs) have
      been observed in sporadic neurocognitive and cardiovascular disorders. We
      explored this mechanism in 382 genomes of 116 early-onset cancer case-parent
      trios and unaffected siblings. Unique de novo germline CNVs were not observed in
      107 breast or colon cancer trios or controls but were indeed found in 7% of 43
      testicular germ cell tumor trios; this percentage exceeds background CNV rates
      and suggests a rare de novo genetic paradigm for susceptibility to some human
      malignancies.

PMID- 22863193
TI  - Optimal unified approach for rare-variant association testing with application to
      small-sample case-control whole-exome sequencing studies.
AB  - We propose in this paper a unified approach for testing the association between
      rare variants and phenotypes in sequencing association studies. This approach
      maximizes power by adaptively using the data to optimally combine the burden test
      and the nonburden sequence kernel association test (SKAT). Burden tests are more
      powerful when most variants in a region are causal and the effects are in the
      same direction, whereas SKAT is more powerful when a large fraction of the
      variants in a region are noncausal or the effects of causal variants are in
      different directions. The proposed unified test maintains the power in both
      scenarios. We show that the unified test corresponds to the optimal test in an
      extended family of SKAT tests, which we refer to as SKAT-O. The second goal of
      this paper is to develop a small-sample adjustment procedure for the proposed
      methods for the correction of conservative type I error rates of SKAT family
      tests when the trait of interest is dichotomous and the sample size is small.
      Both small-sample-adjusted SKAT and the optimal unified test (SKAT-O) are
      computationally efficient and can easily be applied to genome-wide sequencing
      association studies. We evaluate the finite sample performance of the proposed
      methods using extensive simulation studies and illustrate their application using
      the acute-lung-injury exome-sequencing data of the National Heart, Lung, and
      Blood Institute Exome Sequencing Project.

PMID- 22863194
TI  - Exome sequencing identifies FUS mutations as a cause of essential tremor.
AB  - Essential tremor (ET) is a common neurodegenerative disorder that is
      characterized by a postural or motion tremor. Despite a strong genetic basis, a
      gene with rare pathogenic mutations that cause ET has not yet been reported. We
      used exome sequencing to implement a simple approach to control for misdiagnosis
      of ET, as well as phenocopies involving sporadic and senile ET cases. We studied
      a large ET-affected family and identified a FUS p.Gln290(*) mutation as the cause
      of ET in this family. Further screening of 270 ET cases identified two additional
      rare missense FUS variants. Functional considerations suggest that the pathogenic
      effects of ET-specific FUS mutations are different from the effects observed when
      FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET
      FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas
      amyotrophic lateral sclerosis FUS mutant transcripts are not.

PMID- 22863196
TI  - Transcutaneous application of pulsed radiofrequency treatment for shoulder pain.
AB  - We report a retrospective audit of transcutaneous pulsed radiofrequency treatment
      therapy (TCPRFT) for shoulder pain over a 4-year period. METHODS:   Electronic
      and manual case review revealed that TCPRFT had been performed on 13 patients,
      with 15 painful shoulders, using a single treatment session between 2006 and 2010
      in an outpatient setting. RESULTS:   Of the 15 shoulders treated, 10 (two-thirds)
      had pain relief for over 3 months with an average pain score reduction of 6.1 of
      10 and an average duration of pain relief of 395 days. Two experienced pain
      relief of < 3 months with an average reduction in pain score of 4.3 of 10 and an
      average duration of effect of 11 days. Three cases experienced no pain relief
      from the treatment. SUMMARY:   These results suggest TCPRFT may provide
      clinically useful pain relief and be another treatment modality for shoulder
      pain. Our findings justifies further research, and we are proceeding with a
      double-blind placebo randomized controlled studies to determine the efficacy of
      TCPRFT in chronic shoulder pain.

PMID- 22863195
TI  - A mutation in the 5'-UTR of IFITM5 creates an in-frame start codon and causes
      autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus.
AB  - Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous
      disorder associated with bone fragility and susceptibility to fractures after
      minimal trauma. OI type V has an autosomal-dominant pattern of inheritance and is
      not caused by mutations in the type I collagen genes COL1A1 and COL1A2. The most
      remarkable and pathognomonic feature, observed in ~65% of affected individuals,
      is a predisposition to develop hyperplastic callus after fractures or surgical
      interventions. To identify the molecular cause of OI type V, we performed whole
      exome sequencing in a female with OI type V and her unaffected parents and
      searched for de novo mutations. We found a heterozygous de novo mutation in the
      5'-untranslated region of IFITM5 (the gene encoding Interferon induced
      transmembrane protein 5), 14 bp upstream of the annotated translation initiation
      codon (c.-14C>T). Subsequently, we identified an identical heterozygous de novo
      mutation in a second individual with OI type V by Sanger sequencing, thereby
      confirming that this is the causal mutation for the phenotype. IFITM5 is a
      protein that is highly enriched in osteoblasts and has a putative function in
      bone formation and osteoblast maturation. The mutation c.-14C>T introduces an
      upstream start codon that is in frame with the reference open-reading frame of
      IFITM5 and is embedded into a stronger Kozak consensus sequence for translation
      initiation than the annotated start codon. In vitro, eukaryotic cells were able
      to recognize this start codon, and they used it instead of the reference
      translation initiation signal. This suggests that five amino acids (Met-Ala-Leu
      Glu-Pro) are added to the N terminus and alter IFITM5 function in individuals
      with the mutation.

PMID- 22863197
TI  - Silent brain infarction--a review of recent observations.
AB  - Silent brain infarction is a cerebral ischaemic event evident on brain imaging
      without any clinical symptom. Silent brain infarction is often detected in
      apparently healthy, elderly people and in different selected patient groups as
      well. Lately, several studies were carried out in order to identify the clinical
      conditions leading to silent brain infarction. A large number of clinical and
      paraclinical parameters were found to increase silent brain infarction
      prevalence, and the continuously growing list of risk factors revealed that the
      majority of them are similar to those related to stroke. Accordingly, some
      consider silent brain infarction the preclinical stage of clinically overt
      stroke. This point of view emphasizes the early recognition and management of
      silent brain infarction-related risk factors, and a great need for comparative
      studies, which could elicit the most sensitive indicators of the increased silent
      brain infarction risk, especially the ones that could be cost-effectively
      screened in the large populations as well.

PMID- 22863198
TI  - Association of fluoride in water for consumption and chronic pain of body parts
      in residents of San Kamphaeng district, Chiang Mai, Thailand.
AB  - OBJECTIVE: To assess the dose response of fluoride exposure from water and
      chronic pain. METHODS: Using a retrospective cohort design, the study was
      conducted in two sub-districts of San Kamphaeng district, Poo-kha and On-tai.
      Five hundred and thirty-four residents aged >=50 years of age were interviewed
      about their sources of drinking water and assessed for chronic pain. Each water
      source was sampled for fluoride measurement, from which the average daily
      fluoride dose was estimated. Binary logistic regression with forward stepwise
      (likelihood ratio) model selection technique was used to examine the association
      between the average daily fluoride dose and chronic pain. RESULTS: We found
      associations between the average daily fluoride dose and lower back pain [odds
      ratio (OR) = 5.12; 95% confidence interval (CI), 1.59-16.98], and between the
      high fluoride area vs. the low fluoride area (OR = 1.58; 95% CI, 1.10-2.28;
      relative risk= 1.22 with 95% CI, 1.14-1.31) to lower back pain. Other risk
      factors, such as family history of body pain and a history of injury of the lower
      body, were also associated with lower back pain. However, there were no
      relationships between the average daily fluoride dose and leg and knee pains.
      CONCLUSION: To prevent further lower back pain, we recommend that the water in
      this area be treated to reduce its fluoride content.

PMID- 22863199
TI  - Sustainability of healthcare improvement: what can we learn from learning theory?
AB  - BACKGROUND: Changes that improve the quality of health care should be sustained.
      Falling back to old, unsatisfactory ways of working is a waste of resources and
      can in the worst case increase resistance to later initiatives to improve care.
      Quality improvement relies on changing the clinical system yet factors that
      influence the sustainability of quality improvements are poorly understood.
      Theoretical frameworks can guide further research on the sustainability of
      quality improvements. Theories of organizational learning have contributed to a
      better understanding of organizational change in other contexts. To identify
      factors contributing to sustainability of improvements, we use learning theory to
      explore a case that had displayed sustained improvement. METHODS: Forde Hospital
      redesigned the pathway for elective surgery and achieved sustained reduction of
      cancellation rates. We used a qualitative case study design informed by theory to
      explore factors that contributed to sustain the improvements at Forde Hospital.
      The model Evidence in the Learning Organization describes how organizational
      learning contributes to change in healthcare institutions. This model constituted
      the framework for data collection and analysis. We interviewed a strategic sample
      of 20 employees. The in-depth interviews covered themes identified through our
      theoretical framework. Through a process of coding and condensing, we identified
      common themes that were interpreted in relation to our theoretical framework.
      RESULTS: Clinicians and leaders shared information about their everyday work and
      related this knowledge to how the entire clinical pathway could be improved. In
      this way they developed a revised and deeper understanding of their clinical
      system and its interdependencies. They became increasingly aware of how different
      elements needed to interact to enhance the performance and how their own efforts
      could contribute. CONCLUSIONS: The improved understanding of the clinical system
      represented a change in mental models of employees that influenced how the
      organization changed its performance. By applying the framework of organizational
      learning, we learned that changes originating from a new mental model represent
      double-loop learning. In double-loop learning, deeper system properties are
      changed, and consequently changes are more likely to be sustained.

PMID- 22863200
TI  - Interaction of barley powdery mildew effector candidate CSEP0055 with the defence
      protein PR17c.
AB  - A large number of effector candidates have been identified recently in powdery
      mildew fungi. However, their roles and how they perform their functions remain
      unresolved. In this study, we made use of host-induced gene silencing and
      confirmed that the secreted barley powdery mildew effector candidate, CSEP0055,
      contributes to the aggressiveness of the fungus. This result suggests that
      CSEP0055 is involved in the suppression of plant defence. A yeast two-hybrid
      screen indicated that CSEP0055 interacts with members of the barley pathogenesis
      related protein families, PR1 and PR17. Interaction with PR17c was confirmed by
      bimolecular fluorescence complementation analyses. Down-regulation and over
      expression of PR17c in epidermal cells of barley confirmed that this protein is
      important for penetration resistance against the powdery mildew fungus. In line
      with this, PR17c was found to be apoplastic, localizing to the papillae formed in
      response to this fungus. The CSEP0055 transcript did not start to accumulate
      until 24 h after inoculation. This suggests that this gene is expressed too late
      to influence primary penetration events, but rather sustains the fungus at sites
      of secondary penetration, where PR17c appears to be able to accumulate.

PMID- 22863201
TI  - The relationship between BMI and metabolomic profiles: a focus on amino acids.
AB  - The role of metabolomics in the field of nutrition is continuing to grow and it
      has the potential to assist in the understanding of metabolic regulation and
      explain how minor perturbations can have a multitude of biochemical endpoints. It
      is this development, which creates the potential to provide the knowledge
      necessary to facilitate a more targeted approach to nutrition. In recent years,
      there has been interest in applying metabolomics to examine alterations in the
      metabolic profile according to weight gain/obesity. Emerging from these studies
      is the strong evidence that alterations in the amino acid (AA) profiles are
      associated with obesity. Several other studies have also shown a relationship
      between branched-chain amino acids (BCAA), obesity and insulin resistance. The
      present review focuses on the proposed link between AA and in particular BCAA,
      obesity and insulin resistance. In conclusion, a wealth of information is
      accumulating to support the role of AA, and in particular of the BCAA, in
      obesity.

PMID- 22863202
TI  - Development of isoform selective PI3-kinase inhibitors as pharmacological tools
      for elucidating the PI3K pathway.
AB  - Using a parallel synthesis approach to target a non-conserved region of the PI3K
      catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta
      and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The
      compounds had good cellular activity and were selective against protein kinases
      and other members of the PI3K superfamily including mTOR and DNA-PK.

PMID- 22863203
TI  - GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N
      arylbenzamide LRRK2 kinase inhibitor.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for some
      forms of Parkinson's disease. Here we report the discovery and characterization
      of 2-arylmethyloxy-5-subtitutent-N-arylbenzamides with potent LRRK2 activities
      exemplified by GSK2578215A which exhibits biochemical IC(50)s of around 10 nM
      against both wild-type LRRK2 and the G2019S mutant. GSK2578215A exhibits
      exceptionally high selectivity for LRRK2 across the kinome, substantially
      inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S
      mutant at a concentration of 0.3-1.0 MUM in cells and in mouse spleen and kidney,
      but not in brain, following intraperitoneal injection of 100mg/kg.

PMID- 22863204
TI  - Structure-based design, synthesis, and biological evaluation of
      dihydroquinazoline-derived potent beta-secretase inhibitors.
AB  - Structure-based design, synthesis, and biological evaluation of a series of
      dihydroquinazoline-derived beta-secretase inhibitors incorporating thiazole and
      pyrazole-derived P2-ligands are described. We have identified inhibitor 4f which
      has shown potent enzyme inhibitory (K(i)=13 nM) and cellular (IC(50)=21 nM in
      neuroblastoma cells) assays. A model of 4f was created based upon the X-ray
      structure of 3a-bound beta-secretase. The model suggested possible interactions
      in the active site.

PMID- 22863205
TI  - pH-dependent structural conformations of B-phycoerythrin from Porphyridium
      cruentum.
AB  - B-phycoerythrin from the red alga Porphyridium cruentum was crystallized using
      the technique of capillary counter-diffusion. Crystals belonging to the space
      group R3 with almost identical unit cell constants and diffracting to 1.85 and
      1.70 A were obtained at pH values of 5 and 8, respectively. The most important
      difference between structures is the presence of the residue His88alpha in two
      different conformations at pH 8. This residue is placed next to the chromophore
      phycoerythrobilin PEB82alpha and the new conformation results in the relocation
      of the hydrogen-bond network and hydration around PEB82alpha, which probably
      contributes to the observed pH dependence of the optical spectrum associated with
      this chromophore. Comparison with the structures of B-phycoerythrin from other
      red algae shows differences in the conformation of the A-ring of the chromophore
      PEB139alpha. This conformational difference in B-phycoerythrin from P. cruentum
      enables the formation of several hydrogen bonds that connect PEB139alpha with the
      chromophore PEB158beta at the (alphabeta)(3) hexamer association interface. The
      possible influence of these structural differences on the optical spectrum and
      the ability of the protein to perform energy transfer are discussed, with the two
      pH-dependent conformations of His88alpha and PEB82alpha being proposed as
      representing critical structural features that are correlated with the pH
      dependence of the optical spectrum and transient optical states during energy
      transfer.

PMID- 22863206
TI  - A randomized controlled trial of qigong for fibromyalgia.
AB  - INTRODUCTION: Fibromyalgia is difficult to treat and requires the use of multiple
      approaches. This study is a randomized controlled trial of qigong compared with a
      wait-list control group in fibromyalgia. METHODS: One hundred participants were
      randomly assigned to immediate or delayed practice groups, with the delayed group
      receiving training at the end of the control period. Qigong training (level 1
      Chaoyi Fanhuan Qigong, CFQ), given over three half-days, was followed by weekly
      review/practice sessions for eight weeks; participants were also asked to
      practice at home for 45 to 60 minutes per day for this interval. Outcomes were
      pain, impact, sleep, physical function and mental function, and these were
      recorded at baseline, eight weeks, four months and six months. Immediate and
      delayed practice groups were analyzed individually compared to the control group,
      and as a combination group. RESULTS: In both the immediate and delayed treatment
      groups, CFQ demonstrated significant improvements in pain, impact, sleep,
      physical function and mental function when compared to the wait-list/usual care
      control group at eight weeks, with benefits extending beyond this time. Analysis
      of combined data indicated significant changes for all measures at all times for
      six months, with only one exception. Post-hoc analysis based on self-reported
      practice times indicated greater benefit with the per protocol group compared to
      minimal practice. CONCLUSIONS: This study demonstrates that CFQ, a particular
      form of qigong, provides long-term benefits in several core domains in
      fibromyalgia. CFQ may be a useful adjuvant self-care treatment for fibromyalgia.
      TRIAL REGISTRATION: clinicaltrials.gov NCT00938834.

PMID- 22863207
TI  - Feasibility of exercising adults with asthma: a randomized pilot study.
AB  - BACKGROUND: Aerobic exercise appears to have clinical benefits for many
      asthmatics, yet a complete understanding of the mechanisms underlying these
      benefits has not been elucidated at this time. PURPOSE: The objective of this
      study was to determine feasibility for a larger, future study that will define
      the effect of aerobic exercise on cellular, molecular, and functional measures in
      adults with mild-moderate asthma. DESIGN: Recruited subjects were randomized into
      usual care (sedentary) or usual care with moderate intensity aerobic exercise
      treatment groups. SETTING / PARTICIPANTS: Nineteen adults with mild-moderate
      asthma but without a recent history of exercise were recruited at the UAB Lung
      Health Center, Birmingham, AL. INTERVENTION: The exercise group underwent a 12
      week walking program exercising at 60 - 75% of maximum heart rate (HRmax).
      Subjects self-monitored HRmax levels using heart rate monitors; exercise diaries
      and recreation center sign-in logs were also used. MAIN OUTCOME MEASURES:
      Functional measures, including lung function and asthma control scores, were
      evaluated for all subjects at pre- and post-study time-points; fitness measures
      were also assessed for subjects in the exercise group. Peripheral blood and nasal
      lavage fluid were collected from all subjects at pre- and post-study visits in
      order to evaluate cellular and molecular measures, including cell differentials
      and eosinophilic cationic protein (ECP). RESULTS: Sixteen subjects completed the
      prescribed protocol. Results show that subjects randomized to the exercise group
      adhered well (80%) to the exercise prescription and exhibited a trend toward
      improved fitness levels upon study completion. Both groups exhibited improvements
      in ACQ scores. No changes were observed in lung function (FEV1, FEV1/FVC), cell
      differentials, or ECP between groups. CONCLUSIONS: Results indicate that a
      moderate intensity aerobic exercise training program may improve asthma control
      and fitness levels without causing asthma deterioration in adult asthmatics. As
      such, these findings demonstrate the feasibility of the study protocol in
      preparation for a larger, clinical trial that will elucidate the functional
      consequences of aerobic exercise on asthmatic cellular and molecular responses.

PMID- 22863208
TI  - Tuberculosis caused by RDRio Mycobacterium tuberculosis is not associated with
      differential clinical features.
AB  - BACKGROUND: We recently described the Mycobacterium tuberculosis RD(Rio)
      genotype, a clonally derived sublineage within the Latin American-Mediterranean
      (LAM) family. Genetic diversity of M. tuberculosis likely affects the clinical
      aspects of tuberculosis  (TB). Prospective studies that address this issue are
      scarce and remain controversial. OBJECTIVE: To determine the association of
      differential clinical features of pulmonary TB with the RD(Rio) M. tuberculosis
      etiology. METHODS: Culture-proven pulmonary TB patients (n  = 272) were
      clinically evaluated, including history, physical examination, chest X-ray and
      anti-human immunodeficiency virus serology. Isolates were classified as RD(Rio)
      or non-RD(Rio) M. tuberculosis by multiplex polymerase chain reaction and further
      spoligotyped.  Clinical and M. tuberculosis genotype data were analyzed. RESULTS:
      RD(Rio) M. tuberculosis caused disease in 26.5% (72/270) of all TB cases. The LAM
      genotype, of which RD(Rio) strains are members, was responsible for 46.0% of the
      TB cases. Demographic data,  major signs and symptoms, radiographic presentation,
      microbiological features and clinical outcomes were not significantly different
      among patients with TB caused by RD(Rio) and non-RD(Rio) strains. CONCLUSIONS:
      Disease caused by M. tuberculosis RD(Rio)  strains was not clinically distinctive
      or more severe than disease caused by non-RD(Rio) strains in this series of TB
      patients. Larger prospective studies specifically designed to disclose
      differential clinical characteristics of TB caused by specific M. tuberculosis
      lineages  are needed.

PMID- 22863209
TI  - Assessing the human lid margin epithelium using impression cytology.
AB  - PURPOSE: To establish if impression cytology combined with histochemical and
      immunocytochemical staining can be used to assess epithelium of the human upper
      lid margin. METHODS: Following an initial eye examination of 40 healthy subjects
      (19 soft contact lens wearers and 21 non-contact lens wearers, aged 18-57 years),
      lid margin staining was assessed with lissamine green using slit lamp
      biomicroscopy and graded (grade 0-3). Impression cytology of the upper lid margin
      of both eyes was collected, fixed and stained with periodic acid Schiff (PAS) and
      haematoxylin for cell morphology analysis (Nelson grade) or for
      immunocytochemistry (keratinization-related proteins: filaggrin,
      transglutaminase1 (TGase1) and cytokeratin 1/10). RESULTS: In 57% of all
      subjects, grade 0 lissamine green staining showed a thin line (the Marx line),
      just posterior to the meibomian gland ducts. Grade 2 or 3 lissamine green
      staining was observed in 17% of all subjects. There was no difference between
      contact lens and non-contact lens wearers for lid margin staining or Nelson grade
      (p = 0.4, Fisher's exact test). PAS/haematoxylin staining and immunocytochemistry
      showed transition in epithelial cell morphology, with marginal conjunctival
      epithelium, mucocutaneous junction and squamous epithelium, adjacent to meibomian
      gland ducts. This transition in epithelium was associated with differential
      expression of keratinization-related proteins (filaggrin, cytokeratin 1/10 and
      TGase1). CONCLUSION:  Lid margin epithelium can be successfully sampled using
      impression cytology and further characterized using histochemistry and
      immunocytochemistry staining techniques. This approach can be applied to assess
      lid margin changes in conditions such as dry eye and meibomian gland dysfunction.

PMID- 22863210
TI  - Why do students miss lectures? A study of lecture attendance amongst students of
      health science.
AB  - In the domain of health sciences, attendance by students at lectures is more
      critical. Lecture attendance is an issue which has been widely neglected. This
      study aims to determine those factors which affect the lecture attendance. The
      research data was collected by means of a questionnaire during the second
      semester of the academic year 2010-2011 from second-year students of the
      Faculties of Medicine, Pharmacy, Dentistry and Nursing. Together with demographic
      data, the questionnaire includes a Likert-type scale aiming to determine the
      factors influencing attendance at lectures. 663 participated in this study on a
      voluntary basis from Medical, Dentistry, Pharmacy and Nursing Faculties. Raising
      attainment levels, being able to take their own lecture notes, learning which
      aspects of the lecture content were being emphasized, and the opportunity to ask
      questions were amongst the chief reasons for attending lectures. It appears that
      the factors preventing students from attending lectures are mainly individual.
      Amongst the most frequently cited causes of non-attendance, sleeplessness, ill
      health and the inefficiency of lectures in overcrowded halls are emphasized. In
      the totals and sub-dimensions of the Lecture Attendance Scale, Medical Faculty
      students have average scores higher than those of students at other faculties.
      The vital nature of professional expertise and its applications, health sciences
      students' attendance at lectures carries greater importance. It is important to
      strengthen the mentoring system with regard to individual and external factors,
      which have been implicated as having a substantial influence on lecture
      attendance by students.

PMID- 22863211
TI  - Making the nursing curriculum more inclusive for students with specific learning
      difficulties (SpLD): embedding specialist study skills into a core module.
AB  - BACKGROUND: Wray et al. (2012) found that providing specialist 'add on' study
      skills sessions to students with SpLD increased the likelihood of progression and
      earlier identification. However, 48% of students identified as 'at risk' of
      having a SpLD did not pursue further assessment/support, which is of concern.
      OBJECTIVES/DESIGN/PARTICIPANTS/SETTINGS: The study aimed to explore the impact of
      embedding nine study skills sessions designed for students with SpLD into the
      mainstream curriculum on pre-registration nursing students in one HEI in the
      north of England. Two cohorts (September 2009 (n=257) and February 2010 (n=127))
      took part; a total of 300 students completed a student feedback questionnaire
      (201 from September 2009, 99 from February 2010 (response rates of 87% and 80%)).
      The study used an outcome evaluation approach (Watson et al., 2008) to explore
      the impact of the sessions using a range of measures: (i) a student feedback
      questionnaire, (ii) length of time from registration to first contact with
      Disability Services, and (iii) progression data. RESULTS: Overall, the sessions
      were received very positively, especially those on essay writing, reflection and
      learning techniques. Students in the study cohorts made contact with Disability
      Services 4-6 weeks earlier than other cohorts; referrals were also higher.
      Equally, students with SpLD with access to study skills had higher rates of
      progression (e.g. 87% in 2009) than in years with no sessions (e.g. 62% in 2008);
      progression rates were comparable to their non-disabled peers. CONCLUSIONS:
      Mainstreaming what had previously been a reasonable adjustment made time- and
      resource-savings for the institution. Such approaches to embedding are important
      in encouraging and retaining talented and able students.

PMID- 22863212
TI  - Evidence for a multiple sclerosis epidemic?

PMID- 22863213
TI  - Pacific biosciences sequencing technology for genotyping and variation discovery
      in human data.
AB  - BACKGROUND: Pacific Biosciences technology provides a fundamentally new data type
      that provides the potential to overcome some limitations of current next
      generation sequencing platforms by providing significantly longer reads, single
      molecule sequencing, low composition bias and an error profile that is orthogonal
      to other platforms. With these potential advantages in mind, we here evaluate the
      utility of the Pacific Biosciences RS platform for human medical amplicon
      resequencing projects. RESULTS: We evaluated the Pacific Biosciences technology
      for SNP discovery in medical resequencing projects using the Genome Analysis
      Toolkit, observing high sensitivity and specificity for calling differences in
      amplicons containing known true or false SNPs. We assessed data quality: most
      errors were indels (~14%) with few apparent miscalls (~1%). In this work, we
      define a custom data processing pipeline for Pacific Biosciences data for human
      data analysis. CONCLUSION: Critically, the error properties were largely free of
      the context-specific effects that affect other sequencing technologies. These
      data show excellent utility for follow-up validation and extension studies in
      human data and medical genetics projects, but can be extended to other organisms
      with a reference genome.

PMID- 22863214
TI  - Localized gastric amyloidosis differentiated histologically from scirrhous
      gastric cancer using endoscopic mucosal resection: a case report.
AB  - INTRODUCTION: Amyloidosis most often manifests as a systemic involvement of
      multiple tissues and organs, and an amyloidal deposit confined to the stomach is
      extremely rare. It is sometimes difficult to provide a definitive diagnosis of
      localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in
      some cases has been finalized only after surgical resection of the stomach. CASE
      PRESENTATION: A 76-year-old Japanese woman with epigastric discomfort underwent
      an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed
      gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater
      curvature from the upper to the lower part of the gastric corpus. A biopsy
      specimen revealed amyloid deposits in the submucosal layer with no malignant
      findings. We resected a representative portion of the lesion by endoscopic
      mucosal resection using the strip biopsy method to obtain sufficient tissue
      specimens, and then conducted a detailed histological evaluation of the samples.
      The resected specimens revealed deposition of amyloidal materials in the gastric
      mucosa and submucosa without any malignant findings. Congo red staining results
      were positive for amyloidal protein and exhibited green birefringence under
      polarized light. Congo red staining with prior potassium permanganate incubation
      confirmed the light chain (AL) amyloid protein type. Based on these results,
      gastric malignancy, systemic amyloidosis and amyloid deposits induced by
      inflammatory disease were excluded and this lesion was consequently diagnosed as
      localized gastric amyloidosis. Our patient was an older woman and there were no
      findings relative to an increase in gastrointestinal symptoms or anemia, so no
      further treatment was performed. She continued to be in good condition without
      any finding of disease progression six years after verification of our diagnosis.
      CONCLUSIONS: We report an unusual case of primary amyloidosis of the stomach
      resembling scirrhous gastric carcinoma. This case of localized gastric
      amyloidosis was differentiated from scirrhous gastric cancer after performing
      endoscopic mucosal resection without an invasive surgical resection, as
      endoscopic mucosal resection provided sufficient tissue specimens from the lesion
      to make an accurate histological evaluation.

PMID- 22863215
TI  - Availability of exercise facilities and physical activity in 2,037 adults: cross
      sectional results from the Swedish neighborhood and physical activity (SNAP)
      study.
AB  - BACKGROUND: Exercise facilities may have the potential to promote physical
      activity among residents, and to support an active lifestyle throughout the year.
      We investigated the association between objectively assessed availability of
      exercise facilities and objectively assessed physical activity outcomes, and
      whether time of year had a modifying effect on these associations. METHODS: A
      total of 2,037 adults (55% females) wore an accelerometer for seven days. Time
      spent in moderate to vigorous physical activity (minutes per day) and meeting the
      physical activity recommendations (yes/no) were used as outcome variables.
      Availability of exercise facilities was measured within 1,000-meter line-based
      road network buffers around participants' residential addresses using Geographic
      Information Systems. Socio-demographic variables and time of year were included
      as covariates in the analyses. RESULTS: Participants with >=4 exercise facilities
      within their buffer zones spent 5.4 (confidence interval (CI) = 2.3-8.5) more
      minutes in moderate to vigorous physical activity per day, and had 69% higher
      odds (OR = 1.69; CI = 1.39-2.05) of meeting the physical activity
      recommendations, compared to those with no exercise facilities within their
      buffer zones. Time of year had no modifying effect on these associations.
      CONCLUSIONS: Our results show that objective availability of exercise facilities
      was associated with accelerometer-assessed time spent in moderate to vigorous
      physical activity and the odds of meeting the recommended levels of physical
      activity. Neighborhoods may be a logical and potentially significant venue for
      policy interventions aimed at increasing physical activity in the overall
      population.

PMID- 22863217
TI  - Stress hyperglycemia and newly diagnosed diabetes in 2124 patients hospitalized
      with pneumonia.
AB  - OBJECTIVE: Our goal was to determine the association between random admission
      hyperglycemia and new diagnosis of diabetes after discharge in patients
      hospitalized with pneumonia. METHODS: Clinical data, including the Pneumonia
      Severity Index, were prospectively collected on all 2124 patients without
      diabetes admitted with pneumonia to 6 hospitals in Edmonton, Alberta, Canada.
      Admission glucose was classified as: normal (4.0-6.0 mmol/L, reference group)
      versus mild (6.1-7.7 mmol/L), moderate (7.8-11.0 mmol/L), and severe (11.1-20.0
      mmol/L) stress hyperglycemia. New diagnosis of diabetes over 5 years was
      ascertained using well-validated criteria within linked administrative databases.
      Multivariable Cox models were used, and sensitivity, specificity, and likelihood
      ratios were calculated. RESULTS: Mean age was 68 years; 1091 (51%) were male, and
      1418 (67%) had stress hyperglycemia. Over 5 years, 194 (14%) with stress
      hyperglycemia were diagnosed with diabetes. Compared with the 45 of 706 (6%)
      incidences of diabetes in normal glycemia patients (4.0-6.0 mmol/L), a strong
      graded increase in risk of new diabetes existed with increasing hyperglycemia:
      mild (59 of 841 [7%]; adjusted hazard ratio [aHR] 1.09; 95% confidence interval
      [CI], 0.74-1.61) versus moderate (86 of 473 [18%]; aHR 2.99; 95% CI, 2.07-4.31)
      versus severe (49 of 104 [47%]; aHR 11.43; 95% CI, 7.50-17.42). Among moderate-to
      severe hyperglycemia (>=7.8 mmol/L) patients, the sensitivity, specificity, and
      positive and negative likelihood ratios for new diabetes were 57%, 77%, 2.1, and
      0.6, respectively, with a number-needed-to-evaluate of 5 to detect one new case
      of diabetes. CONCLUSION: Moderate-to-severe random hyperglycemia in pneumonia
      patients admitted to the hospital is strongly associated with new diagnosis of
      diabetes. Opportunistic evaluation for diabetes may be warranted in this group.

PMID- 22863216
TI  - Antibodies to hepatitis B virus surface antigen and interleukin 12 and
      interleukin 18 gene polymorphisms in hemodialysis patients.
AB  - BACKGROUND: The interleukin (IL)18 rs360719 CC genotype is associated with the
      development of antibodies to hepatitis B virus surface antigen (anti-HBs) in
      hemodialysis (HD) patients. IL18 shares biological properties with IL12 in
      promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the
      IL12A 3' untranslated region (UTR) and IL12B 3'UTR may contribute to anti-HBs
      development (titre >= 10 IU/L) in HD patients either individually or jointly with
      the IL18 polymorphism. METHODS: In 518 HD patients and 240 controls the IL12A
      rs568408 3'UTR G > A polymorphism was genotyped by high-resolution melting curve
      analysis. Polymerase chain reaction restriction fragment length polymorphism was
      used to detect the IL12B rs3212227 3'UTR A > C and IL18 -1297 T > C rs360719
      polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and
      the risk of impaired anti-HBs development were estimated by computing the odds
      ratios and their 95% confidence intervals using logistic regression analysis.
      RESULTS: In the logistic regression analysis, the higher frequency of rs360719 CC
      individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311
      patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with
      rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or
      rs3212227 AA (p = 0.046) was associated with an increased chance for the
      development of anti-HBs in HD patients. Patients bearing both rs568408 AA and
      rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop
      anti-HBs compared with those carrying any other genotype (p = 0.005) or those who
      had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both
      rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development
      than carriers of any other genotype (p = 0.042). CONCLUSION: Development of anti
      HBs in HD patients is associated with gene polymorphisms of interleukins involved
      in the Th1 system.

PMID- 22863218
TI  - Introducing SurgWiki: a dynamic, free, web-based surgical resource.

PMID- 22863219
TI  - Sentinel node biopsy for breast cancer: then and now.

PMID- 22863220
TI  - Prehospital intubation for traumatic brain injury: do it correctly, or not at
      all.

PMID- 22863221
TI  - Carotid artery stenting: where are we up to with evidence-based practice?

PMID- 22863224
TI  - Metastatic hepatoma of maxillary sinus with atypical presentation.

PMID- 22863225
TI  - Asymptomatic large retroperitoneal cystadenoma.

PMID- 22863226
TI  - Pathognomonic radiological findings of chronic urinary schistosomiasis.

PMID- 22863227
TI  - Penile preservation surgery for basaloid squamous cell carcinoma on the penile
      shaft.

PMID- 22863228
TI  - Retrieval of glove finger post-ICC insertion with a flexible gastroscope.

PMID- 22863229
TI  - Acute exertional paraspinal compartment syndrome.

PMID- 22863230
TI  - Is 18-FDG-PET really that important for the intrahepatic staging of colorectal
      liver metastases?

PMID- 22863231
TI  - Spontaneous intraperitoneal bladder rupture: a demanding diagnosis.

PMID- 22863232
TI  - Spontaneous splenic rupture secondary to metastatic adenocarcinoma of the
      prostate.

PMID- 22863233
TI  - Permissive hypotension in paediatric trauma.

PMID- 22863234
TI  - Rural medical schools and expansion of Australia's translational surgical
      research agenda.

PMID- 22863235
TI  - The value of CRP at admission (Re: ANZ J. Surg. 2012; 82: 52-5).

PMID- 22863236
TI  - Re: The developing clinical problem of chemotherapy-induced hepatic injury.

PMID- 22863237
TI  - Response to Re: Role of fine needle aspiration cytology in the preoperative
      investigation of branchial cysts.

PMID- 22863238
TI  - Parental grief and relationships after the loss of a stillborn baby.
AB  - OBJECTIVES: to describe the grief of mothers and fathers and its influence on
      their relationships after the loss of a stillborn baby. DESIGN: a postal
      questionnaire at three months, one year and two years after stillbirth. SETTING:
      a study of mothers and fathers of babies stillborn during a one-year period in
      the Stockholm region of Sweden. PARTICIPANTS: 55 parents, 33 mothers and 22
      fathers. FINDINGS: mothers and fathers stated that they became closer after the
      loss, and that the feeling deepened over the course of the following year. The
      parents said that they began grieving immediately as a gradual process, both as
      individuals, and together as a couple. During this grieving process their
      expectations, expressions and personal and joint needs might have threatened
      their relationship as a couple, in that they individually felt alone at this time
      of withdrawal. While some mothers and fathers had similar grieving styles, the
      intensity and expression of grief varied, and the effects were profound and
      unique for each individual. KEY CONCLUSIONS: experiences following a loss are
      complex, with each partner attempting to come to terms with the loss and the
      resultant effect on the relationship with their partner. IMPLICATIONS FOR
      PRACTICE: anticipating and being able to acknowledge the different aspects of
      grief will enable professionals to implement more effective intervention in
      helping couples grieve both individually and together.

PMID- 22863239
TI  - Models of maternity care in rural environments: barriers and attributes of
      interprofessional collaboration with midwives.
AB  - OBJECTIVES: interprofessional primary maternity care has emerged as one potential
      solution to the current health human resource shortage in many developed nations.
      This study explores the barriers to and facilitators of interprofessional models
      of maternity care between physicians, nurses, and midwives in rural British
      Columbia, Canada, and the changes that need to occur to facilitate such models.
      DESIGN: a qualitative, exploratory framework guided data collection and analysis.
      SETTING: four rural communities in British Columbia, Canada. Two rural
      communities had highly functional and collaborative interprofessional
      relationships between midwives and physicians, and two communities lacked
      interprofessional activities. PARTICIPANTS: 55 participants were interviewed and
      18 focus groups were conducted with midwives, physicians, labour and delivery
      nurses, public health nurses, community-based providers, birthing women,
      administrators, and decision makers. FINDINGS: in models of interprofessional
      collaboration, primary maternity care providers - physicians, midwives, nurses -
      work together to meet the needs of birthing women in their community. There are
      significant barriers to such collaboration given the disciplinary differences
      between care provider groups including skill sets, professional orientation, and
      funding models. Data analysis confirmed that interprofessional tensions are
      exacerbated in geographically isolated rural communities, due to the stress of
      practicing maternity care in a fee-for-service model with limited health
      resources and a small patient caseload. The participants we spoke with identified
      specific barriers to interprofessional collaboration, including physician and
      nurses' negative perceptions of midwifery and homebirth, inequities in payment
      between physicians and midwives, differences in scopes of practice, confusion
      about roles and responsibilities, and a lack of formal structures for supporting
      shared care practice. Participants expressed that successful interprofessional
      collaboration hinged on strong, mutually respectful relationships between the
      care providers and a clear understanding of team members' roles and
      responsibilities. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: interpersonal
      conflicts between primary maternity care providers in rural communities were
      underpinned by macro-level, systemic barriers to interprofessional practice.
      Financial, legal, and regulatory barriers to interprofessional collaboration must
      be resolved if there is to be increased collaboration between rural midwives and
      physicians. Key recommendations include policy changes to resolve differences in
      scope of practice and inequitable funding between rural midwives and physicians.

PMID- 22863240
TI  - Prevalence of piriformis syndrome in chronic low back pain patients. A clinical
      diagnosis with modified FAIR test.
AB  - PURPOSE: Piriformis syndrome is a collection of symptoms and signs of pain from
      piriformis muscle and is characterized by pain in buttock with variable
      involvement of sciatic nerve. This syndrome is often overlooked in clinical
      practice because its presentation has similarities with other spine pathologies.
      A major problem with the clinical diagnosis of piriformis syndrome is the lack of
      consistent objective findings and an absence of single test that is specific for
      piriformis syndrome. Therefore, a precise and reliable clinical method of
      diagnosing piriformis syndrome should be developed by clinicians. METHODS: This
      is a prospective observational study involving 93 consecutive patients who
      attended the pain management unit for chronic low back pain. The diagnosis of
      piriformis syndrome was made using the modified flexion adduction internal
      rotation (FAIR) test, which is a combination of Lasegue sign and FAIR test.
      Prevalence of piriformis syndrome based on this technique was compared with the
      previous data using other techniques. Chi square (chi2) analysis was performed to
      detect the relationship between piriformis syndrome and the potential risk
      factors. RESULTS: On the basics of our diagnostic criteria, the prevalence of
      piriformis syndrome was 17.2% among low back pain patients. All the patients
      diagnosed with piriformis syndrome responded well with piriformis muscle
      injections. No significant associations were detected between piriformis syndrome
      and spine disorders. CONCLUSIONS: Piriformis syndrome is a painful condition that
      is often overlooked in the differential diagnosis of chronic buttock or low back
      pain. The modified FAIR test together with piriformis muscle injection is
      potentially a reliable method for the clinical diagnosis of piriformis syndrome.

PMID- 22863241
TI  - Peripheral multifocal chorioretinitis: complications, prognosis and relation with
      sarcoidosis.
AB  - PURPOSE: To investigate the prognosis and complications in patients with
      peripheral multifocal chorioretinitis (PMC). PMC is a posterior or panuveitis
      characterized by chronic bilateral vitritis and punched-out lesions in the
      peripheral retina which occurs commonly in elderly white women and is associated
      with sarcoidosis. Prognosis and complications are largely unknown. METHODS: A
      structured literature search in PubMed, Embase and Cochrane was performed to
      identify relevant articles. Articles were screened, and the remaining articles
      were critically appraised based on relevance and validity. RESULTS: The search
      yielded 267 articles. Eight relevant articles were retrieved. All studies
      reported on moderate visual impairment. Macular oedema occurred in 60% of the
      patients with PMC (range, 0-71%), glaucoma in 27% (range, 25-43%) and an
      epiretinal membrane in 21% (range, 0-28%). In total, 47% had proven or presumed
      sarcoidosis. Treatment usually comprised topical corticosteroids, periocular
      steroid injections and systemic corticosteroids regularly in combination with
      methotrexate. CONCLUSION: The prognosis of patients with PMC is characterized by
      a rather poor visual outcome and the relatively high prevalence of complications.
      PMC is strongly associated with sarcoidosis. Solid proof for the treatment
      efficacy of PMC is lacking.

PMID- 22863243
TI  - Mental health in different groups of migrants and ethnic minority within Europe
      and beyond: regional and cross-national challenges and approaches in research,
      practice and training.

PMID- 22863242
TI  - Is serum phosphorus control related to parathyroid hormone control in dialysis
      patients with secondary hyperparathyroidism?
AB  - BACKGROUND: Elevated serum phosphorus (P) levels have been linked to increased
      morbidity and mortality in dialysis patients with secondary hyperparathyroidism
      (SHPT) but may be difficult to control if parathyroid hormone (PTH) is
      persistently elevated. We conducted a post hoc analysis of data from an earlier
      interventional study (OPTIMA) to explore the relationship between PTH control and
      serum P. METHODS: The OPTIMA study randomized dialysis patients with intact PTH
      (iPTH) 300-799 pg/mL to receive conventional care alone (vitamin D and/or
      phosphate binders [PB]; n=184) or a cinacalcet-based regimen (n=368). For
      patients randomized to conventional care, investigators were allowed flexibility
      in using a non-cinacalcet regimen (with no specific criteria for vitamin D
      analogue dosage) to attain KDOQITM targets for iPTH, P, Ca and Ca x P. For those
      assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D
      sterols, and PB were optimized over the first 16 weeks of the study, using a
      predefined treatment algorithm. The present analysis examined achievement of
      serum P targets (<= 4.5 and <= 5.5 mg/dL) in relation to achievement of iPTH <=
      300 pg/mL during the efficacy assessment phase (EAP; weeks 17-23). RESULTS:
      Patients who achieved iPTH <= 300 pg/mL (or a reduction of >= 30% from baseline)
      were more likely to achieve serum P targets than those who did not, regardless of
      treatment group. Of those who did achieve iPTH <= 300 pg/mL, 43% achieved P <=
      4.5 mg/dL and 70% achieved P <= 5.5 mg/dL, versus 21% and 46% of those who did
      not achieve iPTH <= 300 pg/mL. Doses of PB tended to be higher in patients not
      achieving serum P targets. Patients receiving cinacalcet were more likely to
      achieve iPTH <= 300 pg/mL than those receiving conventional care (73% vs 23% of
      patients). Logistic regression analysis identified lower baseline P, no PB use at
      baseline and cinacalcet treatment to be predictors of achieving P <= 4.5 mg/dL
      during EAP in patients above this threshold at baseline. CONCLUSIONS: This post
      hoc analysis found that control of serum P in dialysis patients was better when
      serum PTH levels were lowered effectively, regardless of treatment received.
      TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00110890.

PMID- 22863244
TI  - Socio-economic status and emotional distress of female Turkish immigrants and
      native German women living in Berlin.
AB  - BACKGROUND: Many immigrants face more economic strains and hardship than non
      immigrants. Income inequality and an increasing social gap between immigrants and
      non-immigrants in Europe warrant further studies on the impact of socioeconomic
      factors on health in immigrant groups. The purpose of this study was to examine
      the association of socioeconomic status (SES) and emotional distress in women of
      Turkish descent and in women of German descent. METHODS AND SUBJECTS: A total of
      405 women of German or Turkish descent residing in Berlin were interviewed.
      Emotional distress was assessed by the General Health Questionnaire-28 (GHQ-28),
      and SES was examined by level of education, employment status, and income. The
      associations of emotional distress and SES were estimated in multivariate linear
      regression analyses. RESULTS: Unemployment was associated with increased levels
      of emotional distress in all women, with the highest level of distress in the
      group of unemployed Turkish women. The overall SES level was related to a greater
      level of emotional distress in Turkish women, but not in German women (-3.2,
      95%CI -5.9 - -.5; p=.020 vs. -.8, 95%CI -2.7 - 1.2; p=.431). Further stratified
      analyses by relationship status revealed that the association of SES and
      emotional distress only remained significant among single women. CONCLUSION: The
      impact of socioeconomic hardship appears to be complicated by social roles and
      expectations related to these. Further in-depth study of the complex nature of
      the interaction of social roles and socioeconomic position in female Turkish
      immigrants in Germany is needed to better understand differing risk patterns for
      emotional distress.

PMID- 22863245
TI  - Mental health of Turkish women in Germany: resilience and risk factors.
AB  - BACKGROUND: The purpose of the present study was to examine the protective and
      risk factors of mental distress among Turkish women living in Germany. METHOD:
      105 Turkish immigrant women living in Berlin were investigated with measures of
      extraversion/neuroticism (NEO-FFI), general self-efficacy (GSE), social support
      (BSSS), social strain (F-SOZU) and mental distress (GHQ-28). Interrelations
      between psychosocial variables were assessed using simple Pearson correlations.
      RESULTS: In all subjects, social strain (Pearson's r=.26(**), p=.008) and
      neuroticism (r=.34(**), p<.001) were positively associated with mental distress.
      In contrast, perceived self-efficacy (r=-.38(**), p<.001) and extraversion (r=
      .36(**), p<.001) were negatively associated with mental distress. CONCLUSION:
      Protective factors such as extraversion and self-efficacy seem to have a
      buffering effect on the process of migration. However, in addition to
      neuroticism, social strain seems to be positively associated with mental
      distress.

PMID- 22863246
TI  - The influence of stigma on depression, overall psychological distress, and
      somatization among female Turkish migrants.
AB  - BACKGROUND: Even though some studies suggest that in Mediterranean and non
      western cultures more somatic and less psychological symptoms are reported, this
      so-called 'somatization' hypothesis has been challenged. Reviews show that
      somatic symptoms are a core component of depressive episodes regardless of
      cultural background. The expression of symptoms might be related to the
      psychosocial, social and cultural context surrounding the patient rather than
      'ethnicity' or related constructs. Also, stigma associated with mental disorders
      can affect patients'symptom presentation. METHODS: The interrelationships of
      perceived stigmatization (Explanatory Model Interview Catalogue - Stigma Scale),
      depression (Beck Depression Index II), overall psychological distress (Symptom
      Checklist-90-R), and somatic symptoms (The screening for SOMATOFORM SYMPTOMS II)
      was assessed in a sample of female patients with Turkish descent with a diagnosis
      of depression (N=63). RESULTS: Depression, overall psychological distress, and
      somatic symptoms were positively and significantly related. Stigma was positively
      related to depression and overall psychological distress. There was no
      significant relationship between stigma and somatic symptoms, neither among the
      severely depressed group (N=39), nor among the less depressed group (N=24).
      CONCLUSION: The positive relationships between stigma, depression, and overall
      psychological distress indicate that patients who are more depressed and who have
      higher levels of overall psychological distress experience their condition as
      more stigmatizing. Since somatic symptoms and stigma were not related (neither
      positively, nor negatively), it appears that depressive symptoms and other
      symptoms of psychological distress affect concerns about stigmatizing attitudes
      in a way that somatic symptoms do not. This result challenges common assumption
      of the 'somatization'hypothesis, i.e. that depression is 'somatized'because of
      concern about stigmatizing attitudes.

PMID- 22863247
TI  - Translation and adaptation of the Zung Self- Rating Depression Scale for
      application in the bilingual Azerbaijani population.
AB  - BACKGROUND: A self-reported Zung Self-Rating Depression Scale (ZSDS) is
      recognized as a reliable and valid measure for assessment of depressive symptoms,
      applicable cross-culturally. The aim of the study was to adapt ZSDS for
      application in the bilingual Azerbaijani population. METHODS: ZSDS was translated
      into Azerbaijani and Russian. Two pilot studies on small samples (n=30 and n=45)
      were conducted to improve the scale's acceptability. A readability study was
      conducted on a bigger sample of depressed subjects (n=55) and healthy controls
      (n=120). Chronbach's alpha for the total scale, item-test correlations, alpha if
      item deleted, and sensitivity and specificity at various cut-off levels were
      calculated. RESULTS: The drop-out rate was 83.3% at the first pilot study due to
      problems of comprehension of item 5 and culturally unacceptable wording of item
      6. After rewording of the items drop-out reduced to 20%. On the reliability study
      Chronbach's alpha for the total scale was 0.8727, and item-test correlations for
      the most individual items were satisfactory. An optimal cut-off point was 45
      points with sensitivity=90.91%, specificity=80.83%. CONCLUSIONS: Adaptation of
      the Zung Self-Reported Depression Scale improved cultural acceptability of the
      scale in the context of the Azerbaijani study population.

PMID- 22863248
TI  - Construction and interpretation of self-related function and dysfunction in
      Intercultural Psychiatry.
AB  - In several psychiatric disorders, key symptoms are associated with aspects of an
      individual, which are usually referred to as the "self". For example in
      schizophrenia, it has been suggested that the activity of the self and the
      distinction between self and others are impaired. However, such models of the
      self and its dysfunction have been developed among Western societies and may not
      easily be transferred into different cultural settings, which can be
      characterized by alternative concepts of a person's self. This study compares
      traditional Western concepts of the self and its dysfunction with self-concepts
      developed in Caribbean, African and South-East-Asian societies. This review
      demonstrates that "the self" is a fluid concept. Social function and dysfunction
      of such a self-concepts depend on a given cultural context. We argue that the
      cursive concept of the self is culturally constructed around cursive experiences
      which are shared by all human beings. Such universal experiences may include the
      prereflective access to individual thoughts and feelings, an automatic knowledge
      that (at least in non-pathological states) these emotions and cognitions belong
      to my self. Conscious self-reflection and its narrative articulation, on the
      other hand, is necessarily imbued with social and cultural norms, images and
      events, often of conflicting nature.

PMID- 22863249
TI  - The willingness to participate in health research studies of individuals with
      Turkish migration backgrounds: barriers and resources.
AB  - BACKGROUND: Lower participation rates of ethnic minorities in health research
      studies and potential participation barriers are commonly reported. METHODS: Four
      semi-structured focus groups of individuals with Turkish migration backgrounds
      living in Germany were conducted to identify potential participation barriers.
      Documented statements and superscripted presentation cards by the participants
      were evaluated with a qualitative content analysis. RESULTS: The following eight
      potential reasons for the lower participation rates were identified: role of
      women, lack of knowledge, lack of interest, German-Turkish interactions,
      mistrust, anxiety, data privacy protection and benefits of the study.
      Additionally, the following recruitment strategies to enhance participation rates
      were found: public relations, especially word-of-mouth promotion and contacting
      Turkish key figures, (non-) tangible incentives and trust building through
      transparent communication of the project and its conditions. DISCUSSION: The
      findings provide a wide range of potential participation barriers and
      implications that should be considered to enhance the participation rates of
      minority populations. CONCLUSION: The willingness to participate in health
      research studies can be increased through particular efforts, which should be
      tailored to the recruitment of the underrepresented target population.

PMID- 22863250
TI  - Explanatory models and concepts of West African Malian patients with psychotic
      symptoms.
AB  - BACKGROUND: Subjective explanations of illness concepts and disease can differ
      from culture to culture. We examined explanatory models of West African patients
      with schizophrenia in a community-centred department of psychiatry in Mali, West
      Africa. METHODS: Patients and experts volunteered to be interviewed in the
      Department of Psychiatry of the University Hospital, Pont G, in Bamako, the
      capital of Mali. We used semi-structured interviews to explore key psychotic
      symptoms and explanatory models of psychosis in five experts and fifteen patients
      with schizophrenia. All interviews were analysed using computer assisted content
      analysis with the program Atlas.ti. RESULTS: African patients displayed key
      symptoms of schizophrenia such as commenting and imperative voices, inserted
      thoughts and other phenomena of alien control, which were often subjectively
      explained as obsession by witches or jinns. Explanatory models differed depending
      on occidental migration experience and age. The involvement of family members in
      the treatment-setting facilitates inclusion and recovery. Experts emphasized the
      need to integrate traditional and ethno-pharmacological approaches and modern
      medicine to treat their patients in a culture sensitive manner. DISCUSSION: Our
      data suggests a strong influence of illness concepts on the experience of
      psychotic symptoms, treatment expectations and health-related behaviour.

PMID- 22863251
TI  - How to express mental health problems: Turkish immigrants in Berlin compared to
      native Germans in Berlin and Turks in Istanbul.
AB  - The paper explores expressions used by Turkish immigrants in Berlin to delineate
      psychiatric illnesses and psychological problems. These are compared to
      expressions used by native Germans in Berlin and Turks in Istanbul to assess
      possible cultural differences in articulating mental disorders. For this purpose,
      results of a Free Listing carried out with the three above mentioned groups are
      presented. The data suggest that relevant items which are connected to mental
      health issues vary between the groups as well as within the groups, thus showing
      dependency on factors such as education. For the group of Turkish immigrants the
      data further suggest that this group connects psychic stress to family problems.
      Concerning help seeking, Turkish immigrants, like members of the other groups,
      mention professional psychological/psychiatric help as useful for solving mental
      health problems.

PMID- 22863252
TI  - Health services and the treatment of immigrants: data on service use,
      interpreting services and immigrant staff members in services across Europe.
AB  - BACKGROUND: The number of immigrants using health services has increased across
      Europe. For assessing and improving the quality of care provided for immigrants,
      information is required on how many immigrants use services, what interpreting
      services are provided and whether staff members are from immigrant groups.
      METHODS: Structured interviews were conducted with 15 health services (9 primary
      care, 3 emergency departments, 3 mental health) located in areas with high
      immigrant populations in each of 16 European countries (n=240). Responses were
      collected on the availability of data on service use by immigrant patients, the
      provision of interpreting services and immigrant staff members. RESULTS: Data on
      service use by immigrants were recorded by only 15% of services. More than 40% of
      services did not provide any form of interpreting service and 54% of the services
      reported having no immigrant staff. Mental health services were more likely to
      use direct interpreting services, and both mental health and emergency services
      were more likely to have immigrant staff members. DISCUSSION: For assessing and
      improving the quality of care provided for immigrants, there is a need to improve
      the availability of data on service use by immigrants in health services
      throughout Europe and to provide more consistent access to interpreting services.

PMID- 22863253
TI  - The concept of "intercultural opening": the development of an assessment tool for
      the appraisal of its current implementation in the mental health care system.
AB  - The German concept of "intercultural opening" is an approach to facilitating
      migrants' access to the health care system and improving the care they receive.
      No data exist concerning the current status of the implementation of this
      approach in Germany, and the concept has never been analysed in practice. To
      assess the status of "intercultural opening" in the German mental health care
      system and to further analyse the concept, we developed a tool by combining pre
      existing instruments. In order to review the preliminary tool we combined
      experts' knowledge by carrying out a consensusoriented, expert-based Delphi
      process with actual practice by piloting the instrument in each type of
      institution to be assessed. The assessment tool thus developed(1) is the first
      one to evaluate the current status of "intercultural opening" in the community
      mental health care system in Germany from a broad perspective. This paper is
      intended to present the development process of our assessment tool for
      demonstrating the benefits of this approach and as a model for future studies, as
      well as to increase transparency in relation to the current German approach to
      health care structures in dealing with migrants.

PMID- 22863254
TI  - Cross-cultural training in mental health care--challenges and experiences from
      Sweden and Germany.
AB  - Globalization and cultural diversity challenge mental health care in Europe.
      Sensitivity to culture in mental health care benefits effective delivery of care
      to the individual patient and can be a contribution to the larger project of
      building a tolerant multicultural society. Pivotal for improving cultural
      sensitivity in mental health care is knowledge in cross-cultural psychiatry,
      psychology, nursing and related fields among professionals and accordingly
      training of students and mental health professionals. This paper will give an
      overview, and a critical examination, of current conceptualisation of cross
      cultural mental health training. From German and Swedish experiences the need for
      crosscultural training and clinical research on evaluation will be presented.

PMID- 22863255
TI  - Teaching psychiatry and establishing psychosocial services--lessons from
      Afghanistan.
AB  - We describe the extremely limited psychiatric resources of war-torn countries
      like Afghanistan. In such countries, we suggest to apply experience from training
      medical students in industrialized countries to teach a very basic and simplified
      understanding of psychiatric classifications and core diagnostic symptoms to
      medical students (who will later serve in various medical disciplines in regional
      and district hospitals) and to medical staff including nurses and psychosocial
      counsellors working in health posts and district hospitals. We describe such a
      brief but clinically relevant list of symptoms and classifications based on
      experiences with medical student and practitioner training.

PMID- 22863256
TI  - Epilogue. Mental health in different groups of migrants and ethnic minority in
      Europe and beyond.

PMID- 22863257
TI  - Intermittent hyperglycemia due to autonomic nervous system dysfunction: a new
      feature in patients with congenital central hypoventilation syndrome.
AB  - OBJECTIVE: To analyze glycemic profile in children with congenital central
      hypoventilation syndrome, which is characterized by autonomic nervous system
      dysfunction. STUDY DESIGN: We carried out a university hospital-based
      observational study. Participants included 14 patients assessed from 2007 to 2009
      with a median age of 7.6 (25th-75th percentiles, 1.5-9.6) years at the time of
      the study. Glucose metabolism was assessed by calculating 24-hour plasma glucose
      (before and after meals) and fasting insulin concentrations and carrying out an
      oral glucose tolerance test (OGTT). The main outcome measure was the proportion
      of patients with abnormal glucose concentrations. RESULTS: Abnormal plasma
      glucose concentrations were found in 6 (43%) of the 14 patients with high fasting
      (n = 1) or postprandial (n = 5) hyperglycemia. OGTT was performed in 8 patients,
      of whom 3 (38%) had impaired glucose tolerance. Indices of insulin resistance and
      secretion were normal. No difference in clinical aspects relating to the presence
      of affected organs and/or systems related to central nervous system dysfunction,
      age, or auxology findings was found between patients with normal (43%) and
      abnormal (57%) glucose homeostasis over a 24-hour glycemia cycle or OGTT.
      CONCLUSION: This study provides new information about glucose homeostasis in
      congenital central hypoventilation syndrome, revealing a high incidence of
      hyperglycemia and expanding the spectrum of the disease. It highlights the link
      between autonomic nervous system dysfunction and glycemic dysregulation. Regular,
      long-term monitoring of glucose metabolism is recommended in these patients.

PMID- 22863258
TI  - Safe infant sleep recommendations on the Internet: let's Google it.
AB  - OBJECTIVES: To determine the accuracy of information on infant sleep safety on
      the Internet using Google. We hypothesized that the majority of Web sites would
      accurately reflect the American Academy of Pediatrics (AAP) recommendations for
      infant sleep safety. STUDY DESIGN: We searched for advice using 13 key phrases
      and analyzed the first 100 Web sites for each phrase. Web sites were categorized
      by type and assessed for accuracy of information provided, based on AAP
      recommendations. The accuracy of information was classified as "accurate,"
      "inaccurate," or "not relevant." RESULTS: Overall, 43.5% of the 1300 Web sites
      provided accurate information, 28.1% provided inaccurate information, and 28.4%
      were not relevant. The search terms "infant cigarette smoking," "infant sleep
      position," and "infant sleep surface" yielded the highest percentage of Web sites
      with accurate information. "Pacifier infant," "infant home monitors," and "infant
      co-sleeping" produced the lowest percentage of Web sites with accurate
      information. Government Web sites had the highest rate of accuracy; blogs, the
      lowest. CONCLUSION: The Internet contains much information about infant sleep
      safety that is inconsistent with AAP recommendations. Health care providers
      should realize the extent to which parents may turn to the Internet for
      information about infant sleep safety.

PMID- 22863259
TI  - Secondhand tobacco smoke exposure and severity of influenza in hospitalized
      children.
AB  - OBJECTIVE: To assess whether children with influenza who are exposed to
      secondhand tobacco smoke (SHS) would have more severe illness than those not
      exposed. STUDY DESIGN: We abstracted charts from pediatric inpatients with
      confirmed influenza from 2002-2009 for demographics, medical history, and smoke
      exposure. Severity indicators included intensive care, intubation, and length of
      stay (LOS) in the hospital; potential confounding factors included demographics
      and the presence of asthma or chronic conditions. All chi(2), t tests, and
      regression analyses were run using SPSS v. 18.0. RESULTS: Of 117 children, 40%
      were exposed to SHS, who had increased need for intensive care (30% vs 10%, P <
      .01) and intubation (13% vs 1%, P < .05), and had longer LOS (4.0 vs 2.4 days, P
      < .01). Children with chronic conditions and SHS exposure required more intensive
      care (53% vs 18%, P < .05) and had longer LOS (10.0 vs 3.5 days, P < .01) than
      children not exposed to SHS with chronic conditions. In multivariate analyses
      controlling for potential confounding factors, children with SHS exposure were
      4.7 times more likely to be admitted to intensive care (95% CI 1.4-18.5) and had
      a 70% longer LOS (95% CI 12%-230%). CONCLUSIONS: Children with SHS exposure who
      are hospitalized with influenza have more severe illness. Efforts are needed to
      immunize this population against influenza, and eliminate children's exposure to
      SHS.

PMID- 22863260
TI  - Inflammatory markers in induced sputum of school children born before 32
      completed weeks of gestation.
AB  - OBJECTIVE: To test whether chronic bronchial inflammation may be a contributing
      risk factor for persistent airflow limitation in children born before 32 weeks of
      gestation in later life. STUDY DESIGN: Thirty-six of 160 children born before 32
      completed weeks of gestation who were born between 1988 and 1992 were recruited
      at a median age of 11 years. Eighteen age-matched children born at term were
      controls; 47% of the premature infants and 61% of the term born children produced
      sputum of sufficient quality for interleukin (IL)-8, cell numbers, and
      differential counts. RESULTS: Compared with term born children, sputum from the
      premature group had a higher proportion of neutrophils (62% vs 3.8%; P < .001)
      and higher IL-8/protein values (1.93 MUg/g vs 0.64 MUg/g; P = .008). Forced
      expiratory flow 25%-75% and forced expiratory volume in 1 second/vital capacity
      were significantly lower (73.4 % vs 116% predicted, P = .002 and 97% vs 101%, P =
      .012, respectively). Lung function values and sputum indices did not correlate.
      IL-8/protein and neutrophil percentages correlated significantly with decreasing
      gestational age (Spearman rank coefficient = -0.58, P = .020 and -.70, P =.03
      respectively). CONCLUSION: A significant proportion of school children born very
      preterm demonstrate persistent peripheral airway obstruction that is accompanied
      by neutrophilic lower airway inflammation.

PMID- 22863261
TI  - The role of the mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium
      bovis BCG in host cell interaction.
AB  - BACKGROUND: Mycobacterium tuberculosis differs from most pathogens in its ability
      to multiply inside monocytes and to persist during long periods of time within
      granuloma in a status of latency. A class of proteins called mycobacterial
      histone-like proteins has been associated with regulation of replication and
      latency, but their precise role in the infection process has yet to be uncovered.
      Our study aimed at defining the impact of the histone-like protein MDP1 from M.
      bovis BCG (mycobacterial DNA-binding protein 1, corresponding to Rv2986c from M.
      tuberculosis) on early steps of infection. RESULTS: Previously, a BCG (Bacillus
      Calmette Guerin) strain had been generated by antisense-technique exhibiting
      reduced MDP1 expression. This strain was now used to analyse the impact of
      reduced amount of MDP1 on the interaction with human blood monocytes, macrophage
      lines and PBMC (peripheral blood mononuclear cells). MDP1 was revealed to be
      required for growth at acidic pH and for intracellular replication in human blood
      monocytes. Down-regulation of MDP1 resulted in reduced secretion of the cytokine
      IL-1beta by infected human PBMC. In addition, a reduction of MDP1 expression had
      a major impact on the formation of fused multi-nucleated macrophages. In monocyte
      preparations from human blood as well as in human and mouse macrophage cell
      lines, both the percentage of multi-nucleated cells and the number of nuclei per
      cell were much enhanced when the monocytes were infected with BCG expressing less
      MDP1. CONCLUSION: MDP1 from M. bovis BCG affects the growth at acidic pH and the
      intracellular replication in human monocytes. It furthermore affects cytokine
      secretion by host cells, and the formation of fused multi-nucleated macrophages.
      Our results suggest an important role of MDP1 in persistent infection.

PMID- 22863262
TI  - The Escherichia coli GTPase ObgE modulates hydroxyl radical levels in response to
      DNA replication fork arrest.
AB  - Obg proteins are universally conserved GTP-binding proteins that are essential
      for viability in bacteria. Homologs in different organisms are involved in
      various cellular processes, including DNA replication. The goal of this study was
      to analyse the structure-function relationship of Escherichia coli ObgE with
      regard to DNA replication in general and sensitivity to stalled replication forks
      in particular. Defined C-terminal chromosomal deletion mutants of obgE were
      constructed and tested for sensitivity to the replication inhibitor hydroxyurea.
      The ObgE C-terminal domain was shown to be dispensable for normal growth of
      E.coli. However, a region within this domain is involved in the cellular response
      to replication fork stress. In addition, a mutant obgE over-expression library
      was constructed by error-prone PCR and screened for increased hydroxyurea
      sensitivity. ObgE proteins with substitutions L159Q, G163V, P168V, G216A or
      R237C, located within distinct domains of ObgE, display dominant-negative effects
      leading to hydroxyurea hypersensitivity when over-expressed. These effects are
      abolished in strains with a single deletion of the iron transporter TonB or
      combined deletions the toxin/antitoxin modules RelBE/MazEF, strains both of which
      have been shown to be involved in a pathway that stimulates hydroxyl radical
      formation following hydroxyurea treatment. Moreover, the observed dominant
      negative effects are lost in the presence of the hydroxyl radical scavenger
      thiourea. Together, these results indicate involvement of hydroxyl radical
      toxicity in ObgE-mediated protection against replication fork stress.

PMID- 22863263
TI  - Impact of hepatitis C on survival in dialysis patients: a link with
      cardiovascular mortality?
AB  - Recent evidence has been accumulated showing that anti-HCV-positive serologic
      status is significantly associated with lower survival in dialysis populations,
      but the mechanisms underlying this negative relationship are still unclear. The
      aim of this study was to conduct a systematic review of the published medical
      literature concerning the impact of hepatitis C virus (HCV) infection on all
      cause and disease-specific mortality of patients on regular dialysis. The
      relative risk of all-cause, cardiovascular and liver disease-related mortality
      was regarded as the most reliable outcome end-point. Study-specific relative
      risks were weighted by the inverse of their variance to obtain fixed- and random
      effect pooled estimates for mortality with HCV across the published studies. We
      identified fourteen observational studies involving 145 608 unique patients on
      long-term dialysis. Pooling of study results demonstrated that anti-HCV antibody
      was an independent and significant risk factor for death in patients on
      maintenance dialysis. The summary estimate for adjusted relative risk (all-cause
      mortality) was 1.35 with a 95% confidence interval (CI) of 1.25-1.47. Stratified
      analysis showed that the adjusted RR for liver disease-related death was 3.82
      (95% CI, 1.92; 7.61); heterogeneity statistics, R(i) = 0.58 (P-value by Q-test =
      0.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10;
      1.45); no heterogeneity was found (NS). This meta-analysis of observational
      studies indicates that anti-HCV-positive patients on dialysis have an increased
      risk of either liver or cardiovascular disease-related mortality compared with
      anti-HCV-negative patients. Further studies are in progress to understand better
      the link between HCV and cardiovascular risk among patients on maintenance
      dialysis.

PMID- 22863264
TI  - Genetic polymorphism in cyclooxygenase-2 promoter affects hepatic inflammation
      and fibrosis in patients with chronic hepatitis C.
AB  - Cyclooxygenase (COX)-2 is involved in inflammation, anti-apoptosis and
      carcinogenesis. The -1195GG genotype of single nucleotide polymorphism (SNP) in
      COX-2 promoter was associated with low platelet counts in patients with chronic
      hepatitis C. Polymorphism of patatin-like phospholipase domain-containing protein
      3 (PNPLA3) gene (rs738409 C>G) have been reported to be associated with
      cirrhosis, and the major genotype of SNPs near interleukin (IL)28B are related to
      viral clearance. The present study was designed to assess the contribution of
      these SNPs to disease progression in patients with chronic hepatitis C. The study
      enrolled 220 Japanese patients with chronic hepatitis C. Three SNPs, -1195 COX-2,
      PNPLA3 and IL28B (rs8099917), were genotyped in order to analyze their
      association with hepatic fibrosis and inflammation. The -1195GG genotype in COX-2
      was associated with advanced fibrosis and higher levels of inflammation in the
      liver tissues. The major genotype of IL28B was also associated with advanced
      fibrosis, but the polymorphism of PNPLA3 was neither associated with fibrosis nor
      inflammation. Multivariate analysis showed that -1195GG in COX-2 is an
      independent factor associated with advanced fibrosis, while the major genotype of
      IL28B and HCV genotype 2 were other independent factors. In conclusion, the 
      1195GG genotype in COX-2 is a genetic marker for liver disease progression, while
      the PNPLA3 genotypes are not associated with disease progression in Japanese
      patients with chronic hepatitis C.

PMID- 22863265
TI  - An open-label randomized controlled study of pegylated interferon/ribavirin
      combination therapy for chronic hepatitis C with versus without fluvastatin.
AB  - Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of
      care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C
      virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC
      treatment has been suggested to be effective for better outcome in retrospective
      pilot analyses. We investigated whether the combination of fluvastatin with PEG
      IFN/ribavirin could actually improve sustained viral response (SVR) in patients
      with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled
      study was conducted between July 2008 and December 2009 in 101 chronic hepatitis
      C patients allocated to PEG-IFN/ribavirin combination therapy with or without
      fluvastatin. SVR rates were calculated in groups, stratifying host and viral
      factors. We also analyzed predictive factors for SVR among patients on
      fluvastatin with multivariate regression analysis. Rapid and early virological,
      and end of treatment response rates in the fluvastatin group were not
      significantly different from those in the non-fluvastatin group. Notwithstanding,
      SVR rate was significantly higher in the fluvastatin group than in the non
      fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups
      stratifying demographic data and HCV characteristics showed significantly higher
      SVR rates to more than 80% in males, more than two mutations in the interferon
      sensitivity determining region (ISDR), and a history of relapse among the
      fluvastatin group than the non-fluvastatin group. Being male and major genotype
      IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors
      for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin
      combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in
      patients with HCV genotype 1b and high viral load. Male and major genotype IL28B
      SNPs were independent predictors for SVR among patients on fluvastatin
      combination therapy.

PMID- 22863266
TI  - Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C
      virus genotype 2/3.
AB  - Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human
      albumin/recombinant interferon (IFN)-alpha-2b, with ~200-h half-life.
      Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with
      chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to
      one of four open-label treatment groups: pegylated IFN (Peg-IFN)-alpha-2a 180 MUg
      qwk or albIFN 900, 1200 or 1500 MUg q4wk, plus oral ribavirin 800 mg/day, for 24
      weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA
      <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and
      78% with Peg-IFNalpha-2a and albIFN 900, 1200 and 1500 MUg, respectively (P =
      NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4)
      were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not
      influenced by interleukin 28B genotype, although rapid virologic response rates
      were greater with interleukin 28B CC (P = NS). Serious adverse event rates were
      as follows: 4%, 11%, 3% and 3% with Peg-IFNalpha-2a and albIFN 900, 1200 and 1500
      MUg, respectively. No increase in serious/severe respiratory events was noted
      with albIFN. Fewer absolute neutrophil count reductions <750/mm(3) occurred with
      albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions
      <10 g/dL were less frequent with albIFN 900 and 1200 MUg vs 1500 MUg and Peg
      IFNalpha-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN
      administered q4wk produced fewer haematologic reductions than Peg-IFNalpha-2a,
      but had numerically lower SVR rates (P = NS) in patients with chronic HCV
      genotype 2/3.

PMID- 22863267
TI  - Concentration-guided ribavirin dosing with darbepoetin support and peg-IFN alfa
      2a for treatment of hepatitis C recurrence after liver transplantation.
AB  - Relapse of hepatitis C virus infection after liver transplantation is universal.
      Standard-of-care (SOC) treatment for relapse offers less satisfactory treatment
      response than in nontransplanted patients. Tolerance for treatment is suboptimal
      and withdrawals owing to adverse events induced by treatment frequent. To improve
      tolerance for SOC, and ribavirin (RBV) in particular, concentration-guided RBV
      dosing calculated by a formula taking renal function and weight into
      consideration was utilized. A serum RBV concentration of 10 MUm was set as the
      goal. All patients were given maintenance darbepoetin therapy from 2 weeks prior
      to initiation of treatment. In total, 21 patients with a mean age of 52 (range 25
      64) years were included. The mean RBV concentration at week 4 was 10.2 and 7.36
      MUm in genotype 1/4 and non-1/4 patients, respectively, and 11.7 and 9.42 at week
      12. The mean haemoglobin drop was 25 g/L vs 21 g/L in the genotype 1/4 and non
      1/4 group, respectively, a nonsignificant difference. With this treatment
      approach, 80-90% of patients could be kept adherent to treatment. Sustained viral
      response was achieved 8/16 (50%) with low-grade fibrosis (fibrosis stage <= 2) vs
      in none of five patients with advanced fibrosis (Fibrosis stage 3 and 4), P <
      0.05. We conclude that a treatment algorithm utilizing concentration-guided RBV
      dosing during darbepoetin maintenance therapy substantially improves tolerance
      and allows high adherence to a SOC treatment schedule, and that therapy needs to
      be initiated before advanced fibrosis is developed.

PMID- 22863268
TI  - Peginterferon-Alpha_2B plus ribavirin is more effective than peginterferon
      Alpha_2A plus ribavirin in menopausal women with chronic hepatitis C.
AB  - Under-enrolment of women to randomized clinical trials, including chronic
      hepatitis C, has long been recognized. The aim of this study was to identify
      factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin
      antiviral therapy in relation to gender and reproductive status of female
      patients involved. Seven hundred and forty-six treatment-naive patients (431 men,
      315 women) treated with Peg-IFNalpha-2a (180 MUg/week) or Peg-IFNalpha-2b (1.5
      MUg/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48 weeks were studied
      between 2006 and 2010. Differences in SVR rate, overall and by gender were
      assessed after adjustment and propensity score matching. SVR was obtained in
      44.2% of Peg-IFNalpha-2a-treated patients and in 51.2% of Peg-IFNalpha-2b-treated
      patients (intention-to-treat; P = 0.139). Age, fibrosis stage and genotype 2 and
      3 were independently associated with SVR by multivariate analysis. Analysing by
      gender, the difference in SVR between PEG-IFNalpha types was not significant in
      men but highly significant in women (Peg-IFNalpha-2a:39.1%vs Peg-IFNalpha
      2b:54.4%, P = 0.007). This was attributable to a higher SVR rate with Peg
      IFNalpha-2b in the difficult postmenopausal population (26.9% Peg-IFNalpha-2a vs
      46.0% Peg-IFNalpha-2b, P = 0.040). In women, absence of menopause, genotype 2
      hepatitis C virus infection and use of Peg-IFNalpha-2b were independently
      associated with SVR. In conclusion, predictive factors for SVR are different in
      men and women. Factors differing between genders are menopause, severe steatosis
      and peg-interferon used. The higher SVR rate with Peg-IFNalpha-2b in menopausal
      women is likely attributable to more favourable pharmacokinetics that allows Peg
      IFNalpha-2b to reach visceral fat and oppose the increased cytokine production
      and enhanced inflammatory status in menopause.

PMID- 22863269
TI  - Interleukin-28B (IL-28B) single-nucleotide polymorphisms and interferon plus
      ribavirin treatment outcome in Italian chronically HCV-infected patients.
AB  - To determine the single or combined effect of both rs12979860 and rs8099917 SNPs
      on HCV treatment response, these variants were genotyped in samples from a cohort
      of 170 patients infected with different HCV genotypes (HCVGT). The favourable
      rs12979860 CC genotype was found only in patients with sustained or rapid
      virological responses (SVR/RVR) and at significantly high proportions in HCVGT1/4
      SVR patients. A significant association was also found between the rs8099917 TT
      genotype and SVR in both HCVGT1/4 and HCVGT2/3 groups of patients. In contrast,
      we found that there was significantly more of the rs8099917 GG genotype in
      nonresponders (NR) than in SVR patients which suggests a good association of the
      minor homozygote GG with the lack of treatment response. The combination of
      rs12979860/rs8099917 CC/TT favourable genotypes was found only in SVR patients
      and matched the frequency observed for their rs12979860 CC genotypes alone. By
      contrast, the inverse unfavourable correlate rs12979860/rs8099917 TT/GG genotype
      was seen more in NR than in SVR patients as observed for the single GG genotype.
      This study confirms the impact of both rs12979860 and/or rs8099917 IL-28B SNPs on
      treatment-induced clearance of HCV-RNA and demonstrates that the rs12979860 CC
      genotype is stronger than rs8099917 TT genotype in predicting a positive
      treatment response in HCVGT1/4 patients. The unfavourable rs8099917 GG genotype
      seems to be more important in predicting the failure of treatment response
      independently from HCV genotype.

PMID- 22863270
TI  - Noninvasive assessment of liver fibrosis via spleen stiffness measurement using
      acoustic radiation force impulse sonoelastography in patients with chronic
      hepatitis B or C.
AB  - Portal hypertension and splenomegaly are common in patients with cirrhosis.
      However, there is limited previous in vivo research on the correlation between
      spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the
      diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation
      force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients
      with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness
      measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating
      characteristic curves estimated the diagnostic performance of SSM, with multiple
      linear regression models for LSM and SSM determining the significance of
      explanatory factors. Results indicated significant correlation between LSM and
      SSM (R(2) = 0.574, P < 0.0001). Using SSM to classify METAVIR fibrosis (METAVIR
      F) scores, the areas under curves were 0.839 (95% CI: 0.780-0.898) for METAVIR F1
      vs F2-4, 0.936 (95% CI: 0.898-0.975) for F1-2 vs F3-4 and 0.932 (95% CI: 0.893
      0.971) for F1-3 vs F4, all P < 0.001. Multiple linear regression models
      identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine
      aminotransferase, international normalized ratio of prothrombin time, sodium and
      platelet count as significant independent explanatory factors for liver stiffness
      (adjusted R(2) = 0.724, P < 0.001). Male gender, liver stiffness, METAVIR F2, F3
      and F4 also significantly and independently explained spleen stiffness (adjusted
      R(2) = 0.647, P < 0.001). ARFI SSM is potentially useful as a single or adjunct
      predictor of stages of liver fibrosis.

PMID- 22863271
TI  - Recombinant Semliki Forest virus vectors encoding hepatitis B virus small surface
      and pre-S1 antigens induce broadly reactive neutralizing antibodies.
AB  - Most hepatitis B virus (HBV) vaccines consist of viral small surface (S) protein
      subtype adw2 expressed in yeast cells. In spite of good efficacy, HBV-genotype
      and subtype differences, escape mutants and insufficient Th1 activation remain
      potential problems. To address these problems, we generated recombinant Semliki
      Forest virus (rSFV) vectors encoding S protein, subtype adw2 or ayw2, or a
      fragment of the large surface protein, amino acids 1-48 of the pre-S1 domain,
      fused to S (pre-S1.1-48/S). The antigen loop in S protein and the selected pre-S1
      sequences are known targets of neutralizing antibodies. BALB/c mice were
      immunized intravenously with 10(7) rSFV particles and 10(8) rSFV particles 3
      weeks later. Antibodies induced by rSFV encoding S proteins reacted
      preferentially with subtype determinants of yeast-derived S antigen but equally
      well with patient-derived S antigen. Immunization with rSFV encoding pre-S1.1
      48/S resulted in formation of pre-S1- and S-specific immunoglobulin G (IgG),
      while immunization with the isogenic mutant without S start codon induced pre-S1
      antibodies only. Neutralizing antibodies were determined by mixing with plasma
      derived HBV/ayw2 and subsequent inoculation of susceptible primary hepatocyte
      cultures from Tupaia belangeri. S/adw2 antisera neutralized HBV/ayw2 as
      effectively as antisera raised with S/ayw2. The pre-S1 antibodies also completely
      neutralized HBV infectivity. The IgG1/IgG2a ratios ranged from 0.28 to 0.88 in
      the four immunized groups and were lowest for the pre-S1.1-48/S vector,
      indicating the strongest Th1 response. This vector type may induce subtype
      independent and S-escape-resistant neutralizing antibodies against HBV.

PMID- 22863272
TI  - Prevalence of hepatitis B virus infection among persons with diagnosed diabetes
      mellitus in the United States, 1999-2010.
AB  - The prevalence of hepatitis B virus (HBV) infection among persons with diabetes
      has not been assessed among the US population, despite increasing reports of HBV
      transmission in institutional care settings. Using national survey data, we found
      a 60% higher prevalence of HBV infection among persons with (vs without)
      diagnosed diabetes.

PMID- 22863273
TI  - Haemorrhagic strokes in pregnancy and puerperium.
AB  - There is an increased risk of strokes in pregnancy and puerperium. Intracranial
      haemorrhage is the rarer of the two stroke subtypes but carries a greater
      morbidity and mortality for both the mother and the child. This review highlights
      the causes of pregnancy-related intracranial haemorrhage and its management. The
      incidence varies from region to region with the highest being reported from China
      and Taiwan. Majority of these haemorrhages are secondary to hypertensive
      disorders of pregnancy with smaller proportions related to aneurysm and
      arteriovenous malformation rupture. A small but important contributor is cortical
      venous thrombosis which, although predominantly gives rise to ischaemic lesions,
      may lead to parenchymal haemorrhages as well. Presentation is usually with
      headaches or seizures, with or without focal deficits. Diagnosis requires brain
      imaging with computerized tomography or magnetic resonance imaging, and the
      necessity of investigation when this diagnosis is suspected supersedes the small
      risk of fetal malformation. Management follows the general management principles
      for intracranial haemorrhage management. Blood pressures need to be strictly
      monitored and medicines used for controlling them may differ slightly due to
      teratogenic effects. For preeclampsia, early but safe delivery is the best
      treatment. For cortical venous thrombosis, low-molecular-weight heparin is the
      preferred agent. Aneurysms and vascular malformations need to be definitively
      treated to prevent re-bleed and this can be achieved through surgical or
      endovascular procedures. The timing of surgery depends on neurosurgical
      considerations. However, the timing and mode of delivery are governed by
      obstetric factors. Risk of future haemorrhage depends on whether the underlying
      aetiology can be and has been definitively treated.

PMID- 22863274
TI  - New approach to the study of intraosseous vasculature.
AB  - BACKGROUND: The study of intraosseous vasculature has always been challenging due
      to the hard, calcified structure of bone. Techniques used to study intraosseous
      vasculature usually involve diaphanization with a Spalteholz technique, followed
      by X-ray imaging to display the radio contrast-injected blood vessels. These
      techniques produce results with fine detail when successfully executed. However,
      high failure rates and the extensive length of time required to perform these
      techniques are drawbacks. This paper describes a faster, alternative method for
      the study of intraosseous vasculature. METHOD: Five embalmed and two fresh
      shoulder girdles were harvested from six cadavers. Cannulas were inserted into
      the origins of the anterior (ACHA) and posterior (PCHA) circumflex humeral
      arteries and injected with ink diluted in water or 6% hydrogen peroxide. The
      arteries and their branches were dissected until they entered their respective
      bony foraminae. A hammer, chisel, bone nibbler and mounted needles were used to
      follow the intraosseous course of these arteries and their branches. RESULTS: The
      intraosseous vasculature was seen in all specimens. The branches of the main
      nutrient artery to the proximal humerus were followed until they reached
      articular cartilage or crossed cortical bone again to enter the rotator cuff
      tendons. DISCUSSION: An innovative, new approach to the study of intraosseous
      vasculature with direct visualization of the intraosseous arteries of the
      proximal humerus is described.

PMID- 22863275
TI  - Non-seatbelt use and associated factors among Thai drivers during Songkran
      festival.
AB  - BACKGROUND: Road traffic accidents are the second largest cause of burden of
      disease in Thailand, largely attributable to behavioural risk factors including
      drinking and driving, speeding, substance abuse and failure to use seatbelts. The
      aim of this study was to assess the prevalence and associated factors of non
      seatbelt use among drivers during Songkran festival in Thailand. METHODS: A cross
      sectional survey has been performed to determine the prevalence of seatbelt use
      among Thai drivers (N=13722) during four days of the Songkran festival. For this
      sample the population of drivers was consecutively selected from 12 petrol
      stations in four provinces from each of the four main geographical regions of
      Thailand. The study was conducted at petrol stations at roads in town, outside
      town and highway at different time intervals when trained field staff
      administered a structured questionnaire and performed an observation checklist on
      seat belt use. RESULTS: An overall prevalence of 28.4% of non-seatbelt use among
      drivers was found. In multivariable analysis demographics (being male, younger
      age, coming from the Northern or Southern region in Thailand), environmental
      factors (earlier during the Songkran festival, in the morning and late evening
      and on main roads in town), seatbelt use experiences and attitudes (having been
      in an accident before, never having used a seatbelt, no intention to use a
      seatbelt, lack of awareness of danger of non-seatbelt use and lower perceived
      risk of being caught with non-seatbelt use) and lower exposure to road safety
      awareness (RSA) campaign (less frequent exposure to RSA campaign, less frequent
      following of RTI statistics and not talking with others about the RSA campaign)
      were associated with non-seatbelt use. CONCLUSION: Rates of non-seatbelt use by
      Thai drivers during Songkran festival was 28.4%. Lower exposure to the RSA
      campaign was found to be associated with non-seatbelt use among drivers during
      the Songkran festival.

PMID- 22863276
TI  - Specialized multi-disciplinary heart failure clinics in Ontario, Canada: an
      environmental scan.
AB  - BACKGROUND: Multi-disciplinary heart failure (HF) clinics have been shown to
      improve outcomes for HF patients in randomized clinical trials. However, it is
      unclear how widely available specialized HF clinics are in Ontario. Also, the
      service models of current clinics have not been described. It is therefore
      uncertain whether the efficacy of HF clinics in trials is generalizable to the HF
      clinics currently operating in the province. METHODS: As part of a comprehensive
      evaluation of HF clinics in Ontario, we performed an environmental scan to
      identify all HF clinics operating in 2010. A semi-structured interview was
      conducted to understand the scope of practice. The intensity and complexity of
      care offered were quantified through the use of a validated instrument, and
      clinics were categorized as high, medium or low intensity clinics. RESULTS: We
      identified 34 clinics with 143 HF physicians. We found substantial regional
      disparity in access to care across the province. The majority of HF physicians
      were cardiologists (81%), with 81% of the clinics physically based in hospitals,
      of which 26% were academic centers. There was a substantial range in the
      complexity of services offered, most notably in the intensity of education and
      medication management services offered. All the clinics focused on ambulatory
      care, with only one having an in-patient focus. None of the HF clinics had a home
      based component to care. CONCLUSIONS: Multiple HF clinics are currently operating
      in Ontario with a wide spectrum of care models. Further work is necessary to
      understand which components lead to improved patient outcomes.

PMID- 22863277
TI  - Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling.
AB  - The Hippo pathway is crucial in organ size control, and its dysregulation
      contributes to tumorigenesis. However, upstream signals that regulate the
      mammalian Hippo pathway have remained elusive. Here, we report that the Hippo
      pathway is regulated by G-protein-coupled receptor (GPCR) signaling. Serum-borne
      lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through
      G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby
      activating YAP and TAZ transcription coactivators, which are oncoproteins
      repressed by Lats1/2. YAP and TAZ are involved in LPA-induced gene expression,
      cell migration, and proliferation. In contrast, stimulation of Gs-coupled
      receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby
      inhibiting YAP function. Thus, GPCR signaling can either activate or inhibit the
      Hippo-YAP pathway depending on the coupled G protein. Our study identifies
      extracellular diffusible signals that modulate the Hippo pathway and also
      establishes the Hippo-YAP pathway as a critical signaling branch downstream of
      GPCR.

PMID- 22863278
TI  - Clinical, immunological and genetic features in eleven Algerian patients with
      major histocompatibility complex class II expression deficiency.
AB  - Presenting processed antigens to CD4+ lymphocytes during the immune response
      involves major histocompatibility complex class II molecules. MHC class II genes
      transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and
      RFXAP. Defects in these factors result in major histocompatibility complex class
      II expression deficiency, a primary combined immunodeficiency frequent in North
      Africa. Autosomal recessive mutations in the RFXANK gene have been reported as
      being the principal defect found in North African patients with this disorder. In
      this paper, we describe clinical, immunological and genetic features of 11
      unrelated Algerian patients whose monocytes display a total absence of MHC class
      II molecules. They shared mainly the same clinical picture which included
      protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis
      revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp
      deletion (named I5E6-25_I5E6+1, also known as 752delG26). Immunological and
      genetic findings in our series may facilitate genetic counselling implementation
      for Algerian consanguineous families. Further studies need to be conducted to
      determine 752delG26 heterozygous mutation frequency in Algerian population.

PMID- 22863279
TI  - Implant removal of osteosynthesis: the Dutch practice. Results of a survey.
AB  - BACKGROUND: The aim of this survey study was to evaluate the current opinion and
      practice of trauma and orthopaedic surgeons in the Netherlands in the removal of
      implants after fracture healing. METHODS: A web-based questionnaire consisting of
      44 items was sent to all active members of the Dutch Trauma Society and Dutch
      Orthopaedic Trauma Society to determine their habits and opinions about implant
      removal. RESULTS: Though implant removal is not routinely done in the
      Netherlands, 89% of the Dutch surgeons agreed that implant removal is a good
      option in case of pain or functional deficits. Also infection of the implant or
      bone is one of the main reasons for removing the implant (> 90%), while making
      money was a motivation for only 1% of the respondents. In case of younger
      patients (< 40 years of age) only 34% of the surgeons agreed that metal implants
      should always be removed in this category. Orthopaedic surgeons are more
      conservative and differ in their opinion about this subject compared to general
      trauma surgeons (p = 0.002). Though the far majority removes elastic nails in
      children (95%).Most of the participants (56%) did not agree that leaving implants
      in is associated with an increased risk of fractures, infections, allergy or
      malignancy. Yet in case of the risk of fractures, residents all agreed to this
      statement (100%) whereas staff specialists disagreed for 71% (p < 0.001).
      According to 62% of the surgeons titanium plates are more difficult to remove
      than stainless steel, but 47% did not consider them safer to leave in situ
      compared to stainless steel. The most mentioned postoperative complications were
      wound infection (37%), unpleasant scarring (24%) and postoperative hemorraghe
      (19%). CONCLUSION: This survey indicates that there is no general opinion about
      implant removal after fracture healing with a lack of policy guidelines in the
      Netherlands. In case of symptomatic patients a majority of the surgeons removes
      the implant, but this is not standard practice for every surgeon.

PMID- 22863280
TI  - Comparison of transcript profiles in different life stages of the nematode
      Globodera pallida under different host potato genotypes.
AB  - The potato cyst nematodes (PCNs) Globodera pallida and Globodera rostochiensis
      are important parasites of potato. PCNs undergo complex biotrophic interactions
      with their hosts that involve gene expression changes in both the nematode and
      the host plant. The aim of this study was to determine key genes that are
      differentially expressed in Globodera pallida life cycle stages and during the
      initiation of the feeding site in susceptible and partially resistant potato
      genotypes. For this purpose, two microarray experiments were designed: (i) a
      comparison of eggs, infective second-stage juveniles (J2s) and sedentary
      parasitic-stage J2s (SJ2); (ii) a comparison of SJ2s at 8 days after inoculation
      (DAI) in the susceptible cultivar (Desiree) and two partially resistant lines.
      The results showed differential expression of G. pallida genes during the stages
      studied, including previously characterized effectors. In addition, a large
      number of genes changed their expression between SJ2s in the susceptible cultivar
      and those infecting partially resistant lines; the number of genes with modified
      expression was lower when the two partially resistant lines were compared.
      Moreover, a histopathological study was performed at several time points (7, 14
      and 30 DAI) and showed the similarities between both partially resistant lines
      with a delay and degeneration in the formation of the syncytia in comparison with
      the susceptible cultivar. Females at 30 DAI in partially resistant lines showed a
      delay in their development in comparison with those in the susceptible cultivar.

PMID- 22863281
TI  - Folate, colorectal cancer and the involvement of DNA methylation.
AB  - Diet is a major factor in the aetiology of colorectal cancer (CRC).
      Epidemiological evidence suggests that folate confers a modest protection against
      CRC risk. However, the relationship is complex, and evidence from human
      intervention trials and animal studies suggests that a high-dose of folic acid
      supplementation may enhance the risk of colorectal carcinogenesis in certain
      circumstances. The molecular mechanisms underlying the apparent dual modulatory
      effect of folate on colorectal carcinogenesis are not fully understood. Folate is
      central to C1 metabolism and is needed for both DNA synthesis and DNA
      methylation, providing plausible biological mechanisms through which folate could
      modulate cancer risk. Aberrant DNA methylation is an early event in colorectal
      carcinogenesis and is typically associated with the transcriptional silencing of
      tumour suppressor genes. Folate is required for the production of S-adenosyl
      methionine, which serves as a methyl donor for DNA methylation events; thereby
      folate availability is proposed to modulate DNA methylation status. The evidence
      for an effect of folate on DNA methylation in the human colon is limited, but a
      modulation of DNA methylation in response to folate has been demonstrated. More
      research is required to clarify the optimum intake of folate for CRC prevention
      and to elucidate the effect of folate availability on DNA methylation and the
      associated impact on CRC biology.

PMID- 22863282
TI  - Patient-controlled versus scheduled, nurse-administered analgesia following
      vaginal reconstructive surgery: a randomized trial.
AB  - OBJECTIVE: To determine whether patient-controlled analgesia or scheduled
      intravenous analgesia provides superior pain relief and satisfaction with pain
      control after vaginal reconstructive surgery. STUDY DESIGN: Fifty-nine women
      scheduled for vaginal reconstructive surgery were enrolled in this randomized
      trial. Operative procedures and postoperative orders were standardized. Visual
      analog scales for pain and satisfaction with pain control were recorded during
      the hospital stay and 2 weeks after surgery. RESULTS: Patients receiving patient
      controlled analgesia had less pain on postoperative day 1, 25 mm vs 39 mm, on
      visual analog scales (P = .007). Although this group used twice as much
      hydromorphone (3.57 mg vs 1.48 mg, P < .001), there was no difference in side
      effects, length of hospital stay, or complications. For the sample overall,
      larger amounts of narcotic used correlated with higher pain scores (r = 0.364, P
      = .009) and worse satisfaction scores (r = -0.348, P = .012). CONCLUSION: In
      patients undergoing vaginal surgery, patient-controlled analgesia offers superior
      pain relief on postoperative day 1 when compared with scheduled, nurse
      administered hydromorphone.

PMID- 22863283
TI  - Pathological response and survival after neoadjuvant therapy for breast cancer: a
      30-year study.
AB  - PURPOSE OF THE RESEARCH: HER2-positive and triple-negative breast cancer (TNBC)
      still have a poor prognosis. Pathological complete response (pCR) is usually
      considered a surrogate marker for outcome. The aim of this study was to
      reconsider these parameters on a large population after a long follow-up. 348
      patients with unilateral breast cancer who received neoadjuvant treatment at our
      institution over 30 years were included. RESULTS: Patients were classified
      according to hormonal receptors (HR) and HER2. Median follow-up was 7 years. pCR
      was significantly lower in HR+/HER2- tumors (P < 0.0001). The 7-year OS rates
      were 76.1% (HR+/HER2-), 60.1% (TNBC), 72.4% (HR+/HER2+), and 49.9% (HR-/HER2+).
      Disease-free survival (DFS) and OS differed significantly according to pCR. Among
      HER2+ patients, pCR rate, DFS and OS were greater with trastuzumab. CONCLUSIONS:
      TNBC and HR-/HER2+ tumors have the worst outcome. pCR remains a significant
      prognostic factor. Trastuzumab strongly improves pCR and survival in HER2+
      tumors.

PMID- 22863284
TI  - Early prediction of pathologic response to neoadjuvant therapy in breast cancer:
      systematic review of the accuracy of MRI.
AB  - Magnetic resonance imaging (MRI) has been proposed to have a role in predicting
      final pathologic response when undertaken early during neoadjuvant chemotherapy
      (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in
      early response prediction. A systematic literature search (to February 2011) was
      performed to identify studies reporting the accuracy of MRI during NAC in
      predicting pathologic response, including searches of MEDLINE, PREMEDLINE,
      EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects,
      range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after
      1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared
      to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or
      bidimensional tumour size, three-dimensional volume, quantitative dynamic
      contrast measurements (volume transfer constant [Ktrans], exchange rate constant
      [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour
      reduction. Thresholds for identifying response varied across studies. Definitions
      of response included pathologic complete response (pCR), near-pCR, and residual
      tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity
      across MRI parameters and the outcome definition precluded statistical meta
      analysis. Based on descriptive presentation of the data, sensitivity/specificity
      pairs for prediction of pathologic response were highest in studies measuring
      reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume
      (pCR or near-pCR), at high thresholds (typically >50%); lower
      sensitivity/specificity pairs were evident in studies measuring reductions in uni
      or bidimensional tumour size. However, limitations in study methodology and data
      reporting preclude definitive conclusions. Methods proposed to address these
      limitations include: statistical comparison between MRI parameters, and MRI vs
      other tests (particularly ultrasound and clinical examination); standardising MRI
      thresholds and pCR definitions; and reporting changes in NAC based on test
      results. Further studies adopting these methods are warranted.

PMID- 22863286
TI  - Approach to treatment of hypophosphatemia.
AB  - Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate
      depletion is common in the hospital setting and results in significant morbidity
      and mortality. Chronic hypophosphatemia, often associated with genetic or
      acquired renal phosphate-wasting disorders, usually produces abnormal growth and
      rickets in children and osteomalacia in adults. Acute hypophosphatemia may be
      mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe (<1
      mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism,
      diabetic ketoacidosis, malnutrition/starvation, and after surgery (particularly
      after partial hepatectomy) and in the intensive care unit. Phosphate replacement
      can be given either orally, intravenously, intradialytically, or in total
      parenteral nutrition solutions. The rate and amount of replacement are
      empirically determined, and several algorithms are available. Treatment is
      tailored to symptoms, severity, anticipated duration of illness, and presence of
      comorbid conditions, such as kidney failure, volume overload, hypo- or
      hypercalcemia, hypo- or hyperkalemia, and acid-base status. Mild/moderate acute
      hypophosphatemia usually can be corrected with increased dietary phosphate or
      oral supplementation, but intravenous replacement generally is needed when
      significant comorbid conditions or severe hypophosphatemia with phosphate
      depletion exist. In chronic hypophosphatemia, standard treatment includes oral
      phosphate supplementation and active vitamin D. Future treatment for specific
      disorders associated with chronic hypophosphatemia may include cinacalcet,
      calcitonin, or dypyrimadole.

PMID- 22863285
TI  - IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL
      1beta-mediated degradation of nucleus pulposus in vitro.
AB  - INTRODUCTION: Inflammation plays a key role in the progression of intervertebral
      disc degeneration, a condition strongly implicated as a cause of lower back pain.
      The objective of this study was to investigate the therapeutic potential of
      poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1
      receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL
      1beta) mediated degradative changes in the nucleus pulposus (NP), using an in
      vitro model. METHODS: IL-1ra was encapsulated in PLGA microspheres and release
      kinetics were determined over 35 days. NP agarose constructs were cultured to
      functional maturity and treated with combinations of IL-1beta and media
      conditioned with IL-1ra released from microspheres at intervals for up to 20
      days. Construct mechanical properties, glycosaminoglycan content, nitrite
      production and mRNA expression of catabolic mediators were compared to properties
      for untreated constructs using unpaired Student's t-tests. RESULTS: IL-1ra
      release kinetics were characterized by an initial burst release reducing to a
      linear release over the first 10 days. IL-1ra released from microspheres
      attenuated the degradative effects of IL-1beta as defined by mechanical
      properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA
      expression of inflammatory mediators for 7 days, and continued to limit
      functional degradation for up to 20 days. CONCLUSIONS: In this study, we
      successfully demonstrated that IL-1ra microspheres can attenuate the degradative
      effects of IL-1beta on the NP for extended periods. This therapeutic strategy may
      be appropriate for treating early-stage, cytokine-mediated disc degeneration.
      Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model
      of disc degeneration, as a prelude to clinical translation.

PMID- 22863287
TI  - Treatment outcomes for workers compensation patients in a U.S.-based
      interdisciplinary pain management program.
AB  - OBJECTIVES:  Assess the efficacy of an outpatient-based interdisciplinary pain
      rehabilitation program for patients with active workers compensation claims.
      PATIENTS:  Data were available for 101 patients, primarily with chronic low back
      pain (75%), who participated in the program. METHODS: Treatment included a 4-week
      (Monday to Friday), 8-hours/day graded progressive program that included
      individual and group therapies (pain psychology, physical therapy, occupational
      therapy, relaxation training/biofeedback, aerobic conditioning, pool therapy,
      vocational counseling, patient education and medical management). Outcome
      measures included program completion status, release-to-work status, return-to
      work status, total scores on the Beck depression inventory, state-trait anxiety
      inventory, pain catastrophizing scale, and the McGill pain questionnaire visual
      analogue scale (MPQ VAS). The majority of the patients (65%) graduated from the
      program. Pre-postoutcome data were available for those who graduated from the
      program. For noncompleters, last obtained MPQ VAS was compared with their initial
      MPQ VAS scores. RESULTS: Of those completing the program, most patients (91%)were
      released to return to work; with 80% released to full-time status and 11%
      released to gradual return. Approximately half (49%) of the program completers
      returned to work. Paired-samples t-tests showed that program completers had
      significant reductions in depression (P = 0.000), pain-related catastrophizing (P
      = 0.033), and pain intensity (P = 0.000), but not in anxiety (P = 0.098).
      Interestingly, the last obtained (at early discharge/withdrawal) pain intensity
      scores (M = 70.33) were higher than at baseline (M = 61.20) in the noncompleters.
      This difference was not statistically significant (P = 0.127) but may be
      clinically meaningful. DISCUSSION:  Our results support the efficacy of an
      outpatient-based 4-week interdisciplinary pain rehabilitation program in
      decreasing emotional distress, reducing pain intensity, and improving return-to
      work status in the majority of completers in this challenging population.
      Patients reporting increased pain at discharge or those discharged early may have
      been due to operant factors.

PMID- 22863289
TI  - The risk for chronic kidney disease in patients with heart diseases: a 7-year
      follow-up in a cohort study in Taiwan.
AB  - BACKGROUND: The worldwide increasing trend of chronic kidney disease (CKD) is of
      great concern and the role of heart disease deserves longitudinal studies. This
      study investigated the risk of developing CKD among patients with heart diseases.
      METHODS: From universal insurance claims data in Taiwan, we retrospectively
      identified a cohort of 26005 patients with newly diagnosed heart diseases and
      52010 people without such disease from the 2000-2001 claims. We observed
      prospectively both cohorts until the end of 2007 to measure CKD incidence rates
      in both cohorts and hazard ratios (HR) of CKD. RESULTS: The incidence of CKD in
      the cohort with heart disease was 4.1 times greater than that in the comparison
      cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37
      (95% confidence interval (CI)=2.05-2.74) in the multivariate Cox proportional
      hazard model after controlling for sociodemographic characteristics and
      comorbidity. Compared with individuals aged<40 years, the HRs for CKD ranged from
      2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD
      observed in our patients were also independently associated with hypertension
      (HR=2.26, 95% CI=1.94-2.63) and diabetes mellitus (HR=2.44, 95% CI=2.13-2.80),
      but not with hyperlipidemia (HR=1.13, 95% CI=0.99-1.30). CONCLUSIONS: This
      population study provides evidence that patients with heart disease are at an
      elevated risk of developing CKD. Hypertension and diabetes mellitus are also
      comorbidity associated with increasing the CKD risk independently.

PMID- 22863290
TI  - Macular hole after injection of dexamethasone intravitreal implant for macular
      oedema due to central retinal vein occlusion.

PMID- 22863288
TI  - Antiretroviral therapy initiation during tuberculosis treatment and HIV-RNA and
      CD4 T-lymphocyte responses.
AB  - SETTING: A large human immunodeficiency virus (HIV) clinic in South Africa.
      OBJECTIVE: To examine the effect of initiating antiretroviral therapy (ART) on
      CD4 and viral response at different time periods during anti-tuberculosis
      treatment (<14 days, 15-60 days, or >=60  days) using prospectively collected
      clinical data. METHODS: Cohort data analysis for 1499 patients with tuberculosis
      (TB) and HIV co-infection classified according to timing of ART after the
      initiation of anti-tuberculosis treatment. RESULTS: In adjusted modified Poisson
      regression models,  CD4 and viral responses showed no significant differences
      according to timing of ART initiation (failure to increase CD4 by 6 months, <14
      days vs. >60 days: RR 1.02, 95%CI 0.85-1.22; 15-60 days vs. >60 days: RR 1.00,
      95%CI 0.86-1.15; failure to suppress virus by  6 months, <14 days vs. >60 days:
      RR 0.98, 95%CI 0.59-1.63; 15-60 days vs. >60 days: RR 0.96, 95%CI 0.66-1.41 and
      viral rebound at 12 months, 14 days vs. >60 days: RR 1.43, 95%CI 0.50-4.12; 15-60
      days vs. >60 days: RR 1.14, 95%CI 0.39-3.34).  Similar estimates were found in
      analysis restricted to patients with severe immunosuppression. CONCLUSION:
      Concerns over the overlapping impact of anti-tuberculosis treatment with ART on
      ART response should not be a reason for delaying ART in patients with HIV
      associated TB.

PMID- 22863291
TI  - Serum neurofilament concentrations in children with prolonged febrile seizures.
AB  - OBJECTIVE: Neurofilament (NF) is a major cytoskeletal protein of neurons.
      Elevation of serum NF concentration suggests neuronal injury, especially damage
      to axons. We assessed neuronal damage in febrile seizure (FS) by using NF.
      METHODS: We used enzyme-linked immunosorbent assay to measure serum levels of the
      phosphorylated form of NF-heavy chain (pNF-H) in 42 children with FS and 28
      controls. RESULTS: Serum pNF-H levels in children with prolonged febrile seizure
      (PFS) (n=29) were significantly higher than those in the controls (p<0.001).
      There were no significant differences in serum pNF-H levels between children with
      simple febrile seizure (n=9) and the controls. There was a significant
      correlation between seizure duration and serum pNF-H levels during the first week
      in children with FS (p=0.022, r=0.37). CONCLUSION: Our results suggest that PFS
      could lead to some degree of neuronal damage even in the absence of abnormal
      clinical neurological findings during the short-term follow up period.

PMID- 22863292
TI  - Pathogenic Mycobacterium bovis strains differ in their ability to modulate the
      proinflammatory activation phenotype of macrophages.
AB  - BACKGROUND: Tuberculosis, caused by Mycobacterium tuberculosis or Mycobacterium
      bovis, remains one of the leading infectious diseases worldwide. The ability of
      mycobacteria to rapidly grow in host macrophages is a factor contributing to
      enhanced virulence of the bacteria and disease progression. Bactericidal
      functions of phagocytes are strictly dependent on activation status of these
      cells, regulated by the infecting agent and cytokines. Pathogenic mycobacteria
      can survive the hostile environment of the phagosome through interference with
      activation of bactericidal responses. To study the mechanisms employed by highly
      virulent mycobacteria to promote their intracellular survival, we investigated
      modulating effects of two pathogenic M. bovis isolates and a reference M.
      tuberculosis H37Rv strain, differing in their ability to multiply in macrophages,
      on activation phenotypes of the cells primed with major cytokines regulating
      proinflammatory macrophage activity. RESULTS: Bone marrow- derived macrophages
      obtained from C57BL/6 mice were infected by mycobacteria after a period of cell
      incubation with or without treatment with IFN-gamma, inducing proinflammatory
      type-1 macrophages (M1), or IL-10, inducing anti-inflammatory type-2 cells (M2).
      Phenotypic profiling of M1 and M2 was then evaluated. The M. bovis strain
      MP287/03 was able to grow more efficiently in the untreated macrophages, compared
      with the strains B2 or H37Rv. This strain induced weaker secretion of
      proinflammatory cytokines, coinciding with higher expression of M2 cell markers,
      mannose receptor (MR) and arginase-1 (Arg-1). Treatment of macrophages with IFN
      gamma and infection by the strains B2 and H37Rv synergistically induced M1
      polarization, leading to high levels of inducible nitric oxide synthase (iNOS)
      expression, and reduced expression of the Arg-1. In contrast, the cells infected
      with the strain MP287/03 expressed high levels of Arg-1 which competed with iNOS
      for the common substrate arginine, leading to lower levels of NO production.
      CONCLUSIONS: The data obtained demonstrated that the strain, characterized by
      increased growth in macrophages, down- modulated classical macrophage activation,
      through induction of an atypical mixed M1/M2 phenotype.

PMID- 22863293
TI  - Mapping the interaction between the cytoplasmic domains of HIV-1 viral protein U
      and human CD4 with NMR spectroscopy.
AB  - Viral protein U (VpU) of HIV-1 plays an important role in downregulation of the
      main HIV-1 receptor CD4 from the surface of infected cells. Physical binding of
      VpU to newly synthesized CD4 in the endoplasmic reticulum is an early step in a
      pathway leading to proteasomal degradation of CD4. In this study, regions in the
      cytoplasmic domain of VpU involved in CD4 binding were identified by NMR
      spectroscopy. Amino acids in both helices found in the cytoplasmic region of VpU
      in membrane-mimicking detergent micelles experience chemical shift perturbations
      upon binding to CD4, whereas amino acids between the two helices and at the C
      terminus of VpU show no or only small changes, respectively. The topology of the
      complex was further studied with paramagnetic relaxation enhancement.
      Paramagnetic spin labels were attached at three sequence positions of a CD4
      peptide comprising the transmembrane and cytosolic domains of the receptor. VpU
      binds to a membrane-proximal region in the cytoplasmic domain of CD4.

PMID- 22863294
TI  - Amelogenin splice isoforms stimulate chondrogenic differentiation of ATDC5 cells.
AB  - OBJECTIVE: Amelogenins are the most abundant matrix proteins in enamel. Among the
      amelogenin isoforms, full-length amelogenin (M180) and leucine-rich amelogenin
      peptide (LRAP) are expressed in various tissues and are implicated as signalling
      molecules in mesenchymal cells. Here, we examined the effects of M180 and LRAP on
      a chondrogenic cell line, ATDC5, to investigate the role of amelogenins in
      chondrogenesis. MATERIALS AND METHODS: Recombinant mouse M180- or LRAP-protein
      containing medium or control medium was mixed with a chondrogenesis-stimulating
      medium, and changes in the phenotype, gene expression levels and cell
      proliferation of cultured ATDC5 cells were analysed. RESULTS: The addition of
      amelogenins increased alkaline phosphatase activity and glycosaminoglycan
      secretion at 14 and 21 days of culture, respectively, as compared with the
      control. Quantitative PCR (Q-PCR) analysis revealed that LRAP increased the gene
      expression levels of Runx2, Col2a1 and Aggrecan at 7 days of differentiation.
      Moreover, both M180 and LRAP significantly increased the gene expression levels
      of ALP, Aggrecan, Col10a1 and osteopontin at 28 days of culture.
      Bromodeoxyuridine assay and Q-PCR analysis for Wnt signalling indicated that both
      M180 and LRAP reduced proliferation, but induced the cell differentiation
      possibly through altered non-canonical Wnt signalling. CONCLUSION: M180 and LRAP
      accelerate chondrogenic differentiation and maturation of ATDC5 cells.

PMID- 22863295
TI  - Behavioural antecedents to pro re nata psychotropic medication administration on
      acute psychiatric wards.
AB  - This study examined the antecedents to administration of pro re nata (PRN)
      psychotropic medication on acute psychiatric wards, with a particular focus on
      its use in response to patient aggression and other conflict behaviours. A sample
      of 522 adult in-patients was recruited from 84 acute psychiatric wards in
      England. Data were collected from nursing and medical records for the first 2 
      weeks of admission. Two-thirds of patients received PRN medication during this
      period, but only 30% of administrations were preceded by patient conflict
      (usually aggression). Instead, it was typically administered to prevent
      escalation of patient behaviour and to help patients sleep. Overall, no conflict
      behaviours or further staff intervention occurred after 61% of PRN
      administrations. However, a successful outcome was less likely when medication
      was administered in response to patient aggression. The study concludes that
      improved monitoring, review procedures, training for nursing staff, and
      guidelines for the administration of PRN medications are needed.

PMID- 22863297
TI  - Cycling in physiology.

PMID- 22863296
TI  - Expansion of discharge planning system in Japan: Comparison of results of a
      nationwide survey between 2001 and 2010.
AB  - BACKGROUND: In response to the rapid aging of the population in Japan, many care
      systems have been created in quick succession. Establishment of discharge
      planning departments (DPDs) in hospitals is one of them. In this study, we
      compared the distribution and characteristics of DPDs and the characteristics of
      the hospitals that have DPDs between 2001 and 2010 in Japan. METHODS: We mailed a
      questionnaire about the characteristics of hospitals and existence and situation
      of DPDs to all general hospitals with 100 or more general beds in 2001 and in
      2010. RESULTS: In 2001, of the 3,268 hospitals queried, 1,568 (48.0%) responded
      and 1,357 (41.5%) were selected for data analysis. In 2010, among 2,600
      hospitals, 940 hospitals (36.1%) responded and 913 (35.1%) met the inclusion
      criteria. The percentage of hospitals with DPDs increased from 30% to more than
      70% between the two surveys. More departments were under the direct control of
      the hospital director and more physicians participated in discharge planning
      activities in 2010 than in 2001. In 2001, private hospitals and hospitals with an
      affiliated institution or agency tended to have a DPD; however, the relationship
      between these factors and the presence of a DPD had disappeared in 2010. Larger
      hospitals and hospitals with more nurses per patient tended to have a DPD both in
      2001 and 2010. CONCLUSIONS: Since 2008, the establishment of a DPD has been
      directly connected to medical fees so hospital administrators might have
      recognized the DPD as a "necessary and paid for" department. Having a DPD was the
      majority's policy in Japan, and we must recognize the importance of quality
      assurance through DPDs from now on, especially in small hospitals.

PMID- 22863298
TI  - Exercise and creatine supplementation attenuate recovery from myocardial
      ischaemia.

PMID- 22863299
TI  - Case-finding of dementia in general practice and effects of subsequent
      collaborative care; design of a cluster RCT.
AB  - BACKGROUND: In the primary care setting, dementia is often diagnosed relatively
      late in the disease process. Case finding and proactive collaborative care may
      have beneficial effects on both patient and informal caregiver by clarifying the
      cause of cognitive decline and changed behaviour and by enabling support, care
      planning and access to services.We aim to improve the recognition and diagnosis
      of individuals with dementia in general practice. In addition to this diagnostic
      aim, the effects of case finding and subsequent care on the mental health of
      individuals with dementia and the mental health of their informal carers are
      explored. METHODS AND DESIGN:  DESIGN: cluster randomised controlled trial with
      process evaluation. PARTICIPANTS: 162 individuals >= 65 years, in 15 primary care
      practices, in whom GPs suspect cognitive impairment, but without a dementia
      diagnosis.Intervention; case finding and collaborative care: 2 trained practice
      nurses (PNs) invite all patients with suspected cognitive impairment for a brief
      functional and cognitive screening. If the cognitive tests are supportive of
      cognitive impairment, individuals are referred to their GP for further
      evaluation. If dementia is diagnosed, a comprehensive geriatric assessment takes
      place to identify other relevant geriatric problems that need to be addressed.
      Furthermore, the team of GP and PN provide information and support. CONTROL: GPs
      provide care and diagnosis as usual.Main study parameters: after 12 months both
      groups are compared on: 1) incident dementia (and MCI) diagnoses and 2) patient
      and caregiver quality of life (QoL-AD; EQ5D) and mental health (MH5; GHQ 12) and
      caregiver competence to care (SSCQ). The process evaluation concerns facilitating
      and impeding factors to the implementation of this intervention. These factors
      are assessed on the care provider level, the care recipient level and on the
      organisational level. DISCUSSION: This study will provide insight into the
      diagnostic yield and the clinical effects of case finding and collaborative care
      for individuals with suspected cognitive impairment, compared to usual care. A
      process evaluation will give insight into the feasibility of this
      intervention.The first results are expected in the course of 2013. TRIAL
      REGISTRATION: NTR3389.

PMID- 22863300
TI  - Analysis of voice impairment in aphasia after stroke-underlying neuroanatomical
      substrates.
AB  - Phonation is a fundamental feature of human communication. Control of phonation
      in the context of speech-language disturbances has traditionally been considered
      a characteristic of lesions to subcortical structures and pathways. Evidence
      suggests however, that cortical lesions may also implicate phonation. We carried
      out acoustic and perceptual analyses of the phonation of /a/ in 60 males with
      aphasia (20 Wernicke's, 20 Broca's, 20 subcortical aphasia) and 20 males matched
      in age with no neurological or speech-language disturbances. All groups with
      aphasia were significantly more impaired on the majority of acoustic and
      perceptual measures as compared with the control speakers. Within the subjects
      with aphasia, subjects with subcortical aphasia were more impaired on most
      measures compared to subjects with Broca's aphasia, and they, in turn, more
      impaired than those with Wernicke's aphasia. Lesions in regions involved in sound
      production-perception result in dysfunction of the entire neurocognitive system
      of articulation-phonological language processing.

PMID- 22863301
TI  - Conditional expression of human beta-hexosaminidase in the neurons of Sandhoff
      disease rescues mice from neurodegeneration but not neuroinflammation.
AB  - This study evaluated whether GM(2) ganglioside storage is necessary for
      neurodegeneration and neuroinflammation by performing beta-hexosaminidase rescue
      experiments in neurons of HexB(-/-) mice. We developed a novel mouse model,
      whereby the expression of the human HEXB gene was targeted to neurons of HexB(-/
      ) mice by the Thy1 promoter. Despite beta-hexosaminidase restoration in neurons
      was sufficient in rescuing HexB(-/-) mice from GM(2) neuronal storage and
      neurodegeneration, brain inflammation persisted, including the presence of large
      numbers of reactive microglia/macrophages due to persisting GM(2) presence in
      this cell type. In conclusion, our results suggest that neuroinflammation is not
      sufficient to elicit neurodegeneration as long as neuronal function is restored.

PMID- 22863302
TI  - Rapid selection and identification of Miscanthus genotypes with enhanced glucan
      and xylan yields from hydrothermal pretreatment followed by enzymatic hydrolysis.
AB  - BACKGROUND: Because many Miscanthus genotypes can be cultivated with relatively
      high productivity and carbohydrate content, Miscanthus has great potential as an
      energy crop that can support large scale biological production of biofuels.
      RESULTS: In this study, batch hydrothermal pretreatment at 180 degrees C for 35
      min followed by enzymatic hydrolysis was shown to give the highest total sugar
      yields for Miscanthus x giganteus cv. Illinois planted in Illinois. High
      throughput pretreatment at 180 degrees C for 35 min and 17.5 min followed by co
      hydrolysis in a multi-well batch reactor identified two varieties out of 80 that
      had significantly higher sugar yields from pretreatment and enzymatic hydrolysis
      than others. The differences in performance were then related to compositions of
      the 80 varieties to provide insights into desirable traits for Miscanthus that
      enhance sugar yields. CONCLUSIONS: High throughput pretreatment and co-hydrolysis
      (HTPH) rapidly identified promising genotypes from a wide range of Miscanthus
      genotypes, including hybrids of Miscanthus sacchariflorus/M. sinensis and
      Miscanthus lutarioriparius, differentiating the more commercially promising
      species from the rest. The total glucan plus xylan content in Miscanthus appeared
      to influence both mass and theoretical yields, while lignin and ash contents did
      not have a predictable influence on performance.

PMID- 22863303
TI  - Minimum incision endoscopic radical cystectomy in patients with malignant tumors
      of the urinary bladder: clinical and oncological outcomes at a single
      institution.
AB  - AIMS: The objectives of this study were to investigate the clinical and
      oncological outcomes of patients with malignant tumors of the urinary bladder
      undergoing minimum incision endoscopic radical cystectomy (MIE-RC). METHODS:
      Between August 2005 and June 2011, 130 consecutive patients at Hirosaki
      University Hospital underwent MIE-RC and bilateral lymphadenectomy for malignant
      tumors of the urinary bladder. We retrospectively studied all 130 patients. MIE
      RC was performed through a 7-cm suprapubic midline incision. A 30 degrees 
      laparoscope was conveniently positioned on the head side of the patients, for
      precise observation and monitoring. RESULTS: The median operative time for all
      procedures, including MIE-RC, bilateral pelvic lymphadenectomy and urinary
      diversion was 266 min. The median estimated blood loss was 1260 mL. None of the
      patients had positive surgical margins. The post-operative median follow-up
      period was 32.8 months. The 5-year overall and disease-free survival rates were
      91.6% and 87.0%, respectively. CONCLUSIONS: Our experience with MIE-RC appears to
      be favorable with acceptable operative and oncological outcomes.

PMID- 22863304
TI  - Tumor size of hepatocellular carcinoma in noncirrhotic liver: a controversial
      predictive factor for outcome after resection.
AB  - BACKGROUND: Hepatocellular carcinoma in noncirrhotic liver (NC-HCC) presents
      usually with large size, which is seen as a contraindication to liver
      transplantation (LT) or even resection. The objective of our single-center study
      was to identify prognostic factors following resection of large NC-HCCs and to
      subsequently devise a treatment strategy (including LT) in selected patients.
      METHODS: From 2000 to 2010, 89 patients who had hepatic resection for NC-HCC
      (large >= 8 cm in 52) were analyzed with regard to pathological findings,
      postoperative and long-term outcome. RESULTS: Five patients died postoperatively.
      After a mean follow-up of 35 +/- 30 months, NC-HCC recurred in 36 patients (26/47
      survivors in group 8 cm+, 10/37 in group 8 cm-; p = 0.007). Five-year overall
      (OS) and disease-free survival (DFS) rates were significantly worse for group 8
      cm+ (43.4% vs. 89.2% and 39.3% vs. 60.7% for group 8 cm-, p < 0.05). Seven
      patients underwent re-hepatectomy and/or LT for isolated intrahepatic recurrence,
      with 5-year DFS of 57.1%. In a multivariate analysis, the factors associated with
      poor OS and DFS were vascular invasion and tumor size >= 8 cm in the overall
      population and vascular invasion, fibrosis and satellite nodules in group 8 cm+.
      Adjuvant transarterial chemotherapy was a protective factor in group 8 cm+. In 22
      isolated NC-HCC cases with no vascular invasion or fibrosis, tumor size had no
      impact on five-year DFS (85%). CONCLUSIONS: Although patients with NC-HCC >= 8 cm
      had a poorer prognosis, the absence of vascular invasion or fibrosis was
      associated with excellent survival, regardless of the tumor size. In recurrent
      patients, aggressive treatment (including LT) can be considered.

PMID- 22863305
TI  - Roles of ultrasonography and computed tomography in the surgical management of
      cervical lymph node metastases in papillary thyroid carcinoma.
AB  - AIMS: Adequate evaluation and surgical management of cervical lymph node
      metastasis is very important in papillary thyroid carcinoma (PTC). The aim of
      this study was to evaluate the impact of preoperative ultrasonography (US) and
      computed tomography (CT) on the surgical management of cervical lymph node
      metastases in PTC. METHODS: Medical records and imaging findings were
      retrospectively analyzed for 252 patients with PTC who underwent thyroidectomy
      with neck dissection. RESULTS: The sensitivity of both imaging techniques was
      lower in the central neck (US 23%, CT 41%) than in the lateral neck (US 70%, CT
      82%). The specificities of US and CT were 97% and 90% in the central neck, and
      84% and 64% in the lateral neck, respectively. Our surgical plans for therapeutic
      neck dissection were based on imaging findings in 59% of patients who underwent
      lateral compartment neck dissection and in 32.1% of patients who underwent
      central compartment neck dissection, respectively. CONCLUSIONS: The roles of
      preoperative US and CT in surgical planning for central compartment neck
      dissection in PTC are limited because of their low sensitivity in the central
      neck, but US and CT may be useful in cases with non-palpable lateral neck nodes.

PMID- 22863306
TI  - The use of cluster analysis to derive dietary patterns: methodological
      considerations, reproducibility, validity and the effect of energy mis-reporting.
AB  - Over the last three decades, dietary pattern analysis has come to the forefront
      of nutritional epidemiology, where the combined effects of total diet on health
      can be examined. Two analytical approaches are commonly used: a priori and a
      posteriori. Cluster analysis is a commonly used a posteriori approach, where
      dietary patterns are derived based on differences in mean dietary intake
      separating individuals into mutually exclusive, non-overlapping groups. This
      review examines the literature on dietary patterns derived by cluster analysis in
      adult population groups, focusing, in particular, on methodological
      considerations, reproducibility, validity and the effect of energy mis-reporting.
      There is a wealth of research suggesting that the human diet can be described in
      terms of a limited number of eating patterns in healthy population groups using
      cluster analysis, where studies have accounted for differences in sex, age, socio
      economic status, geographical area and weight status. Furthermore, patterns have
      been used to explore relationships with health and chronic diseases and more
      recently with nutritional biomarkers, suggesting that these patterns are
      biologically meaningful. Overall, it is apparent that consistent trends emerge
      when using cluster analysis to derive dietary patterns; however, future studies
      should focus on the inconsistencies in methodology and the effect of energy mis
      reporting.

PMID- 22863307
TI  - Engaging a community in developing an entertainment-education Spanish-language
      radio novella aimed at reducing chronic disease risk factors, Alabama, 2010-2011.
AB  - BACKGROUND: US Hispanics have disproportionate rates of diabetes and other
      chronic diseases. We used the entertainment-education approach to develop a
      Spanish-language radio novella aimed at reducing risk factors for diabetes,
      obesity, and tobacco use. The approach is based on social cognitive theory and
      proposes modeling as a source of vicarious learning of outcome and efficacy
      expectations. COMMUNITY CONTEXT: The Hispanic population in Alabama increased by
      145% between 2000 and 2010. Nearly one-quarter of Hispanics aged 18 to 64 live
      below the federal poverty level, and 49% are uninsured. Several lifestyle factors
      lead to poor health behaviors in this community. Radio is a popular medium among
      Hispanic immigrants. The single local Spanish-language radio station reaches a
      large proportion of the local community and several communities beyond. METHODS:
      Through various methods, including workshops, review sessions, and other feedback
      mechanisms, we engaged stakeholders and community members in developing and
      evaluating a 48-episode radio novella to be broadcast as part of a variety show.
      We tracked participation of community members in all phases. OUTCOME: Community
      members participated significantly in developing, broadcasting, and evaluating
      the intervention. The desired outcome - development of a culturally relevant
      storyline that addresses salient health issues and resonates with the community -
      was realized. INTERPRETATION: Our approach to community engagement can serve as a
      model for other organizations wishing to use community-based participatory
      methods in addressing Hispanic health issues. The radio novella was a unique
      approach for addressing health disparities among our community's Hispanic
      population.

PMID- 22863308
TI  - Missed opportunities for diagnosis and treatment of diabetes, hypertension, and
      hypercholesterolemia in a Mexican American population, Cameron County Hispanic
      Cohort, 2003-2008.
AB  - INTRODUCTION: Diabetes, hypertension, and hypercholesterolemia are common chronic
      diseases among Hispanics, a group projected to comprise 30% of the US population
      by 2050. Mexican Americans are the largest ethnically distinct subgroup among
      Hispanics. We assessed the prevalence of and risk factors for undiagnosed and
      untreated diabetes, hypertension, and hypercholesterolemia among Mexican
      Americans in Cameron County, Texas. METHODS: We analyzed cross-sectional baseline
      data collected from 2003 to 2008 in the Cameron County Hispanic Cohort, a
      randomly selected, community-recruited cohort of 2,000 Mexican American adults
      aged 18 or older, to assess prevalence of diabetes, hypertension, and
      hypercholesterolemia; to assess the extent to which these diseases had been
      previously diagnosed based on self-report; and to determine whether participants
      who self-reported having these diseases were receiving treatment. We also
      assessed social and economic factors associated with prevalence, diagnosis, and
      treatment. RESULTS: Approximately 70% of participants had 1 or more of the 3
      chronic diseases studied. Of these, at least half had had 1 of these 3 diagnosed,
      and at least half of those who had had a disease diagnosed were not being
      treated. Having insurance coverage was positively associated with having the 3
      diseases diagnosed and treated, as were higher income and education level.
      CONCLUSIONS: Although having insurance coverage is associated with receiving
      treatment, important social and cultural barriers remain. Failure to provide
      widespread preventive medicine at the primary care level will have costly
      consequences.

PMID- 22863309
TI  - FGFR1 is amplified during the progression of in situ to invasive breast
      carcinoma.
AB  - INTRODUCTION: Gene amplification is an important mechanism for activating
      oncogenes in malignant tumors. Although amplification of HER2, C-MYC, CCND1 and
      FGFR1 has been reported in breast cancers, their role in the progression of in
      situ to invasive breast carcinoma is unclear. To investigate this question we
      compared the amplification frequencies of these genes in pure ductal carcinoma in
      situ (DCIS), DCIS associated with invasive carcinoma, and invasive carcinoma.
      METHODS: We performed fluorescence in situ hybridization of the selected genes on
      tissue microarrays composed of 179 pure DCIS and 438 invasive carcinomas. Two
      hundred and sixteen of the latter had DCIS components, and in those cases we
      compared gene amplification in the intraductal and invasive components of each
      carcinoma. RESULTS: The rate of amplification of FGFR1 was higher in invasive
      carcinomas than in the pure DCIS, but the opposite was true for HER2
      amplification. These findings applied consistently to high-grade tumors, but not
      to low/intermediate-grade tumors. The amplification status of HER2, C-MYC, CCND1
      and FGFR1 was generally similar in the matched invasive and DCIS components of
      the same tumors. However, FGFR1 amplification was more common in the invasive
      components than in the DCIS components. In survival analyses, FGFR1 amplification
      was found to be an independent prognostic factor for poor disease-free survival
      for all patients with invasive carcinoma and for the hormone receptor-positive
      subgroup. CONCLUSION: Amplification of HER2, C-MYC and CCND1 seems to play a role
      in the early development of breast cancer, but not in its progression. However,
      the increased frequency of FGFR1 amplification in invasive carcinomas compared
      with pure DCIS and in the invasive components of individual tumors, and its
      association with decreased disease-free survival, suggests a role for FGFR1
      amplification in the progression of breast cancer including in situ-to-invasive
      transition, as well as initiation.

PMID- 22863310
TI  - Health-related quality of life and all-cause mortality in patients with diabetes
      on dialysis.
AB  - BACKGROUND: This study tests the hypotheses that health-related quality of life
      (HRQOL) in prevalent dialysis patients with diabetes is lower than in dialysis
      patients without diabetes, and is at least as poor as diabetic patients with
      another severe complication, i.e. foot ulcers. This study also explores the
      mortality risk associated with diabetes in dialysis patients. METHODS: HRQOL was
      assessed using the Short Form-36 Health Survey (SF-36), in a cross-sectional
      study of 301 prevalent dialysis patients (26% with diabetes), and compared with
      diabetic patients not on dialysis (n = 221), diabetic patients with foot ulcers
      (n = 127), and a sample of the general population (n = 5903). Mortality risk was
      assessed using a Kaplan-Meier plot and Cox proportional hazards analysis.
      RESULTS: Self-assessed vitality, general and mental health, and physical function
      were significantly lower in dialysis patients with diabetes than in those
      without. Vitality (p = 0.011) and general health (p <0.001) was impaired in
      diabetic patients receiving dialysis compared to diabetic patients with foot
      ulcers, but other subscales did not differ. Diabetes was a significant predictor
      for mortality in dialysis patients, with a hazard ratio (HR) of 1.6 (95% CI 1.0
      2.5) after adjustment for age, dialysis vintage and coronary artery disease.
      Mental aspects of HRQOL were an independent predictor of mortality in diabetic
      patients receiving dialysis after adjusting for age and dialysis vintage (HR 2.2,
      95% CI 1.0-5.0). CONCLUSIONS: Physical aspects of HRQOL were perceived very low
      in dialysis patients with diabetes, and lower than in other dialysis patients and
      diabetic patients without dialysis. Mental aspects predicted mortality in
      dialysis patients with diabetes. Increased awareness and measures to assist
      physical function impairment may be particularly important in diabetes patients
      on dialysis.

PMID- 22863311
TI  - Impact of second-line drug resistance on tuberculosis treatment outcomes in the
      United States: MDR-TB is bad enough.
AB  - SETTING: The worldwide emergence of extensively drug-resistant tuberculosis (TB)
      has focused attention on treatment with second-line drugs (SLDs). OBJECTIVE: To
      determine the impact on outcomes of resistance to individual SLDs, we analyzed
      successful treatment completion and death  among drug-resistant TB cases in the
      US national TB surveillance system, 1993-2007 (N = 195 518). DESIGN: We defined
      four combinations of first-line drug (FLD) resistance based on isoniazid (INH)
      and rifamycin, and three patterns of SLD resistance: fluoroquinolones, 
      injectable SLDs and other oral SLDs. We compared treatment outcomes of cases by
      FLD resistance, with and without each pattern of SLD resistance. RESULTS: In all
      but one instance, cases with FLD resistance but no SLD resistance had better
      outcomes than cases with SLD resistance. Rifamycin  resistance, alone or with
      INH, resulted in a greater decline in treatment completion and greater increase
      in deaths than resistance to SLDs. Among patients with multidrug-resistant TB,
      additional resistance to injectable SLDs was statistically significant. Outcomes
      were better for human immunodeficiency  virus (HIV) negative than HIV-positive
      cases for all resistance patterns, but improved among HIV-infected cases after
      1998, when highly active antiretroviral treatment became widely available.
      CONCLUSION: These results suggest that the effect of rifamycin resistance may
      outweigh the more  modest effects of resistance to specific SLDs.

PMID- 22863312
TI  - Validation of recall of body weight over a 26-year period in cohort members of
      the Adventist Health Study 2.
AB  - PURPOSE: The validity of recall of past body weight has been measured and tends
      to be high; however, the paucity of validation data for recall in older age is
      noteworthy given the need for accounting for age and disease-related weight
      change in prospective studies. METHODS: The Adventist Health Study-2 (AHS-2) is a
      prospective, questionnaire-based study (n = 96,710) that enrolled a cohort from
      2002 through 2007 to investigate the role of lifestyle exposures (diet, physical
      activity, anthropometrics) and health on outcomes such as cancer and mortality.
      RESULTS: The mean difference between current weight reported 26 years earlier in
      AHS-1 and recall of past body weight in AHS-2 was only 0.67 kg, indicating
      underestimation in the recall of past body weight from ages 30 to 70 years.
      CONCLUSIONS: Misclassification is differential across both age and adiposity, and
      this tendency needs to be incorporated into the interpretation of weight history
      and health outcome literature.

PMID- 22863313
TI  - Mitochondria, maternal inheritance, and male aging.
AB  - The maternal transmission of mitochondrial genomes invokes a sex-specific
      selective sieve, whereby mutations in mitochondrial DNA can only respond to
      selection acting directly on females. In theory, this enables male-harming
      mutations to accumulate in mitochondrial genomes when these same mutations are
      neutral, beneficial, or only slightly deleterious in their effects on females.
      Ultimately, this evolutionary process could result in the evolution of male
      specific mitochondrial mutation loads; an idea previously termed Mother's Curse.
      Here, we present evidence that the effects of this process are broader than
      hitherto realized, and that it has resulted in mutation loads affecting patterns
      of aging in male, but not female Drosophila melanogaster. Furthermore, our
      results indicate that the mitochondrial mutation loads affecting male aging
      generally comprise numerous mutations over multiple sites. Our findings thus
      suggest that males are subject to dramatic consequences that result from the
      maternal transmission of mitochondrial genomes. They implicate the diminutive
      mitochondrial genome as a hotspot for mutations that affect sex-specific patterns
      of aging, thus promoting the idea that a sex-specific selective sieve in
      mitochondrial genome evolution is a contributing factor to sexual dimorphism in
      aging, commonly observed across species.

PMID- 22863314
TI  - Drosophila TRPML is required for TORC1 activation.
AB  - Loss-of-function mutations in TRPML1 (transient receptor potential mucolipin 1)
      cause the lysosomal storage disorder, mucolipidosis type IV (MLIV). Here, we
      report that flies lacking the TRPML1 homolog displayed incomplete autophagy and
      reduced viability during the pupal period--a phase when animals rely on autophagy
      for nutrients. We show that TRPML was required for fusion of amphisomes with
      lysosomes, and its absence led to accumulation of vesicles of significantly
      larger volume and higher luminal Ca(2+). We also found that trpml(1) mutant cells
      showed decreased TORC1 (target of rapamycin complex 1) signaling and a
      concomitant upregulation of autophagy induction. Both of these defects in the
      mutants were reversed by genetically activating TORC1 or by feeding the larvae a
      high-protein diet. The high-protein diet also reduced the pupal lethality and the
      increased volume of acidic vesicles. Conversely, further inhibition of TORC1
      activity by rapamycin exacerbated the mutant phenotypes. Finally, TORC1 exerted
      reciprocal control on TRPML function. A high-protein diet caused cortical
      localization of TRPML, and this effect was blocked by rapamycin. Our findings
      delineate the interrelationship between the TRPML and TORC1 pathways and raise
      the intriguing possibility that a high-protein diet might reduce the severity of
      MLIV.

PMID- 22863315
TI  - Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA
      damage response.
AB  - The DNA damage response (DDR) and DNA repair are critical for maintaining genomic
      stability and evading many human diseases. Recent findings indicate that
      accumulation of SUN1, a nuclear envelope (NE) protein, is a significant
      pathogenic event in Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford
      progeria syndrome, both caused by mutations in LMNA. However, roles of mammalian
      SUN proteins in mitotic cell division and genomic stability are unknown. Here we
      report that the inner NE proteins SUN1 and SUN2 may play a redundant role in DDR.
      Mouse embryonic fibroblasts from Sun1(-/-)Sun2(-/-) mice displayed premature
      proliferation arrest in S phase of cell cycle, increased apoptosis and DNA
      damage, and decreased perinuclear heterochromatin, indicating genome instability.
      Furthermore, activation of ATM and H2A.X, early events in DDR, were impaired in
      Sun1(-/-)Sun2(-/-) fibroblasts. A biochemical screen identified interactions
      between SUN1 and SUN2 and DNA-dependent protein kinase (DNAPK) complex that
      functions in DNA nonhomologous end joining repair and possibly in DDR. Knockdown
      of DNAPK reduced ATM activation in NIH 3T3 cells, consistent with a potential
      role of SUN1- and SUN2-DNAPK interaction during DDR. SUN1 and SUN2 could affect
      DDR by localizing certain nuclear factors to the NE or by mediating communication
      between nuclear and cytoplasmic events.

PMID- 22863316
TI  - A DNA-damage selective role for BRCA1 E3 ligase in claspin ubiquitylation, CHK1
      activation, and DNA repair.
AB  - BACKGROUND: The breast and ovarian cancer suppressor BRCA1 is essential for
      cellular responses to DNA damage. It heterodimerizes with BARD1 to acquire an E3
      ubiquitin (Ub) ligase activity that is often compromised by cancer-associated
      mutations. Neither the significance of this activity to damage responses, nor a
      relevant in vivo substrate, is clear. RESULTS: We have separated DNA-damage
      responses requiring the BRCA1 E3 ligase from those independent of it, using a
      gene-targeted point mutation in vertebrate DT40 cells that abrogates BRCA1's
      catalytic activity without perturbing BARD1 binding. We show that BRCA1
      ubiquitylates claspin, an essential coactivator of the CHK1 checkpoint kinase,
      after topoisomerase inhibition, but not DNA crosslinking by mitomycin C. BRCA1 E3
      inactivation decreases chromatin-bound claspin levels and impairs homology
      directed DNA repair by interrupting signal transduction from the damage-activated
      ATR kinase to its effector, CHK1. CONCLUSIONS: Our findings identify claspin as
      an in vivo substrate for the BRCA1 E3 ligase and suggest that its modification
      selectively triggers CHK1 activation for the homology-directed repair of a subset
      of genotoxic lesions. This mechanism unexpectedly defines an essential but
      selective function for BRCA1 E3 ligase activity in cellular responses to DNA
      damage.

PMID- 22863317
TI  - Membrane-bound myo1c powers asymmetric motility of actin filaments.
AB  - Class I myosins are molecular motors that link cellular membranes to the actin
      cytoskeleton and play roles in membrane tension generation, membrane dynamics,
      and mechanosignal transduction. The widely expressed myosin-Ic (myo1c) isoform
      binds tightly to phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] via a
      pleckstrin homology domain located in the myo1c tail, which is important for its
      proper cellular localization. In this study, we found that myo1c can power actin
      motility on fluid membranes composed of physiological concentrations of
      PtdIns(4,5)P(2) and that this motility is inhibited by high concentrations of
      anionic phospholipids. Strikingly, this motility occurs along curved paths in a
      counterclockwise direction (i.e., the actin filaments turn in leftward circles).
      A biotinylated myo1c construct containing only the motor domain and the lever arm
      anchored via streptavidin on a membrane containing biotinylated lipid can also
      generate asymmetric motility, suggesting that the tail domain is not required for
      the counterclockwise turning. We found that the ability to produce
      counterclockwise motility is not a universal characteristic of myosin-I motors,
      as membrane-bound myosin-Ia (myo1a) and myosin-Ib (myo1b) are able to power actin
      gliding, but the actin gliding has no substantial turning bias. This work reveals
      a possible mechanism for establishing asymmetry in relationship to the plasma
      membrane.

PMID- 22863319
TI  - A genetic basis for altered sexual behavior in mutant female mice.
AB  - Although neural substrates of mammalian female mating behavior have been
      described, the association between complex courtship activity and specific
      underlying mechanisms remains elusive. We have isolated a mouse line that
      unexpectedly shows altered female social behavior with increased investigation of
      males and increased genital biting. We investigated adult individuals by
      behavioral observation and genetic and molecular neuroanatomy methods. We report
      exacerbated inverse pursuits and incapacitating bites directed at the genitals of
      stud males. This extreme deviation from wild-type female courtship segregates
      with a deletion of the Hoxd1 to Hoxd9 genomic region. This dominant Atypical
      female courtship allele (HoxD(Afc)) induces ectopic Hoxd10 gene expression in
      several regions in newborn forebrain transitorily and stably in a sparse
      subpopulation of cells in the cornu ammonis fields of adult hippocampus, which
      may thus lead to an abnormal modulation in the sexual behavior of mutant females.
      The resulting compulsive sexual solicitation behavior displayed by the most
      affected individuals suggests new avenues to study the genetic and molecular
      bases of normal and pathological mammalian affect and raises the potential
      involvement of the hippocampus in the control of female courtship behavior. The
      potential relevance to human 2q.31.1 microdeletion syndrome is discussed.

PMID- 22863318
TI  - A betaPIX-PAK2 complex confers protection against Scrib-dependent and cadherin
      mediated apoptosis.
AB  - BACKGROUND: During epithelial morphogenesis, a complex comprising the betaPIX
      (PAK-interacting exchange factor beta) and class I PAKs (p21-activated kinases)
      is recruited to adherens junctions. Scrib, the mammalian ortholog of the
      Drosophila polarity determinant and tumor suppressor Scribble, binds betaPIX
      directly. Scrib is also targeted to adherens junctions by E-cadherin, where Scrib
      strengthens cadherin-mediated cell-cell adhesion. Although a role for the Scrib
      betaPIX-PAK signaling complex in promoting membrane protrusion at wound edges has
      been elucidated, a function for this complex at adherens junctions remains
      unknown. RESULTS: Here, we establish that Scrib targets betaPIX and PAK2 to
      adherens junctions where a betaPIX-PAK2 complex counterbalances apoptotic stimuli
      transduced by Scrib and elicited by cadherin-mediated cell-cell adhesion.
      Moreover, we show that this signaling pathway regulates cell survival in response
      to osmotic stress. Finally, we determine that in suspension cultures, the Scrib
      betaPIX-PAK2 complex functions to regulate anoikis elicited by cadherin
      engagement, with Scrib promoting and the betaPIX-PAK2 complex suppressing
      anoikis, respectively. CONCLUSIONS: Our findings demonstrate that the Scrib
      betaPIX-PAK2 signaling complex functions as an essential modulator of cell
      survival when localized to adherens junctions of polarized epithelia. The
      activity of this complex at adherens junctions is thereby essential for normal
      epithelial morphogenesis and tolerance of physiological stress. Furthermore, when
      localized to adherens junctions, the Scrib-betaPIX-PAK2 signaling complex serves
      as a key determinant of anoikis sensitivity, a pivotal mechanism in tumor
      suppression. Thus, this work also reveals the need to expand the definition of
      anoikis to include a central role for adherens junctions.

PMID- 22863320
TI  - Homeodomain-containing protein HOXB9 regulates expression of growth and
      angiogenic factors, facilitates tumor growth in vitro and is overexpressed in
      breast cancer tissue.
AB  - HOXB9 is a homeobox-containing gene and is critical for the development of
      mammary gland and sternum. HOXB9 is also regulated by estrogen and is critical
      for angiogenesis. We investigated the biochemical roles of HOXB9 and its
      homeodomain in cell-cycle progression and tumorigenesis. Our studies demonstrated
      that HOXB9 is overexpressed in breast cancer tissue. HOXB9 overexpression
      stimulated 3D formation in soft agar assay. HOXB9 binds to the promoters of
      various tumor growth and angiogenic factors and regulates their expression. The
      homeodomain of HOXB9 plays crucial roles in transcriptional regulation of tumor
      growth factors and also in 3D colony formation, indicating crucial roles of the
      HOXB9 homeodomain in tumorigenesis. Overall, we demonstrated that HOXB9 is a
      critical regulator of tumor growth factors and is associated with tumorigenesis.

PMID- 22863321
TI  - Phenotypic and genomic analysis of hypervirulent human-associated Bordetella
      bronchiseptica.
AB  - BACKGROUND: B. bronchiseptica infections are usually associated with wild or
      domesticated animals, but infrequently with humans. A recent phylogenetic
      analysis distinguished two distinct B. bronchiseptica subpopulations, designated
      complexes I and IV. Complex IV isolates appear to have a bias for infecting
      humans; however, little is known regarding their epidemiology, virulence
      properties, or comparative genomics. RESULTS: Here we report a characterization
      of the virulence of human-associated complex IV B. bronchiseptica strains. In in
      vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in
      comparison to a panel of complex I strains. Some complex IV isolates were
      remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10-
      to 20-fold greater than complex I strains. In vivo, a subset of complex IV
      strains was found to be hypervirulent, with an increased ability to cause lethal
      pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in
      vivo were both dependent on the activity of the bsc T3SS and the BteA effector.
      To clarify differences between lineages, representative complex IV isolates were
      sequenced and their genomes were compared to complex I isolates. Although our
      analysis showed there were no genomic sequences that can be considered unique to
      complex IV strains, there were several loci that were predominantly found in
      complex IV isolates. CONCLUSION: Our observations reveal a T3SS-dependent
      hypervirulence phenotype in human-associated complex IV isolates, highlighting
      the need for further studies on the epidemiology and evolutionary dynamics of
      this B. bronchiseptica lineage.

PMID- 22863323
TI  - Artificially depleted plasmas are not necessarily commutable with native patient
      plasmas for International Sensitivity Index calibration and International
      Normalized Ratio derivation: a reply.

PMID- 22863322
TI  - The effect of caffeine on retinal vessel diameter in young healthy subjects.
AB  - PURPOSE: To investigate the effect of caffeine on retinal vessel diameter before
      and during flicker light stimulation in young healthy subjects. METHODS:
      Seventeen healthy subjects (mean age: 29.6 +/- 3.73 years, range: 22-35 years)
      were included in this study. The diameter of retinal vessels was measured
      continuously with the retinal vessel analyzer (RVA) before and 1 hr after 200 mg
      oral caffeine intake. After baseline assessment, a green luminance flicker of 20
      second duration was applied to stimulate retinal activity. The diameter of a
      segment of an arteriole and of a venule were measured during stimulation and 80
      second after cessation of the stimulus. Flicker stimulation and 80-second
      measurement interval were carried out three times. Blood pressure parameters,
      systemic mean arterial pressure (MAP), ocular perfusion pressure (OPP) and
      intraocular pressure (IOP) were obtained before and after oral caffeine intake.
      RESULTS: The mean diameter of the arterioles at baseline before caffeine intake
      was 123.30 +/- 14.0 MUm (arithmetic mean standard deviation) and after caffeine
      117.30 +/- 13.0 MUm which was significantly different (p=0.004). The mean
      diameter of the venules at baseline before caffeine intake was 147.60 +/- 19.5
      MUm and after caffeine 137.73 +/- 19.9 MUm which was significantly different (p =
      0.005). The mean diameter of the arterioles during flicker light stimulation
      before caffeine intake was 126.65 +/- 13.24 MUm and after caffeine intake 121.59
      +/- 12.12 MUm (p = 0.012). The mean diameter of the venules during flicker light
      stimulation before caffeine intake was 151.87 +/- 18.63 MUm and after caffeine
      intake was 145.14 +/- 19.82 MUm (p = 0.027). The flicker response of the
      arterioles increased from 2.8% before caffeine to 3.8% after caffeine intake (p =
      0.010). The flicker response of the venules increased from 3.4% before caffeine
      to 5.5% after caffeine intake (p = 0.0001). Baseline diameters and diameters
      during flicker light stimulation after caffeine intake showed a significant
      negative correlation to the MAP for the arterioles (baseline: r = -0.338, p =
      0.049 and flicker: r = -0.345, p = 0.046) and the venules (baseline: r = -0.496,
      p = 0.003 and flicker: r =-0.479, p = 0.004). CONCLUSIONS: The present study
      showed a significant vasoconstrictory response of the retinal vessels 1 hr after
      caffeine intake in young healthy subjects. Retinal vessel diameter changes were
      negatively correlated with MAP after caffeine consumption. These effects seem to
      be elicited by an autoregulatory response of the retinal vessels to the increased
      blood pressure changes after caffeine.

PMID- 22863324
TI  - Landscape-scale effects of herbivores on treefall in African savannas.
AB  - Herbivores cause treefalls in African savannas, but rates are unknown at large
      scales required to forecast changes in biodiversity and ecosystem processes. We
      combined landscape-scale herbivore exclosures with repeat airborne Light
      Detection and Ranging of 58 429 trees in Kruger National Park, South Africa, to
      assess sources of savanna treefall across nested gradients of climate,
      topography, and soil fertility. Elephants were revealed as the primary agent of
      treefall across widely varying savanna conditions, and a large-scale 'elephant
      trap' predominantly removes maturing savanna trees in the 5-9 m height range.
      Treefall rates averaged 6 times higher in areas accessible to elephants, but
      proportionally more treefall occurred on high-nutrient basalts and in lowland
      catena areas. These patterns were superimposed on a climate-mediated regime of
      increasing treefall with precipitation in the absence of herbivores. These
      landscape-scale patterns reveal environmental controls underpinning herbivore
      mediated tree turnover, highlighting the need for context-dependent science and
      management.

PMID- 22863325
TI  - Chromosome abnormalities in Indonesian patients with short stature.
AB  - BACKGROUND: Short stature is associated with several disorders including wide
      variations of chromosomal disorders and single gene disorders. The objective of
      this report is to present the cytogenetic findings in Indonesian patients with
      short stature. METHODS: G-banding and interphase/metaphase FISH were performed on
      short stature patients with and without other clinical features who were referred
      by clinicians all over Indonesia to our laboratory during the year 2003-2009.
      RESULTS: The results of chromosomal analysis of ninety seven patients (mean age:
      10.7 years old) were collected. The group of patients with other clinical
      features showed sex chromosome abnormalities in 45% (18/40) and autosomal
      abnormalities in 10% (4/40), whereas those with short stature only, 42.1% (24/57)
      had sex chromosome abnormalities and 1.75% (1/57) had autosomal abnormalities.
      The autosomal chromosomal abnormalities involved mostly subtelomeric regions.
      Results discrepancies between karyotype and FISH were found in 10 patients,
      including detection of low-level monosomy X mosaicism in 6 patients with normal
      karyotype, and detection of mosaic aneuploidy chromosome 18 in 1 patient with
      45,XX,rob(13;14)(q10;q10).Statistical analysis showed no significant association
      between the groups and the type of chromosomal abnormalities. CONCLUSION:
      Chromosome abnormalities account for about 50% of the short stature patients.
      Wide variations of both sex and autosomal chromosomes abnormalities were detected
      in the study. Since three out of five patients had autosomal structural
      abnormalities involving the subtelomeric regions, thus in the future,
      subtelomeric FISH or even a more sensitive method such as genomic/SNP microarray
      is needed to confirm deletions of subtelomeric regions of chromosome 9, 11 and
      18. Low-level mosaicism in normal karyotype patients indicates interphase FISH
      need to be routinely carried out in short stature patients as an adjunct to
      karyotyping.

PMID- 22863326
TI  - Is the high-risk strategy to prevent cardiovascular disease equitable? A
      pharmacoepidemiological cohort study.
AB  - BACKGROUND: Statins are increasingly prescribed to prevent cardiovascular disease
      (CVD) in asymptomatic individuals. Yet, it is unknown whether those at higher CVD
      risk - i.e. individuals in lower socio-economic position (SEP) - are adequately
      reached by this high-risk strategy. We aimed to examine whether the Danish
      implementation of the strategy to prevent cardiovascular disease (CVD) by
      initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals
      is equitable across socioeconomic groups. METHODS:  DESIGN: Cohort study. SETTING
      AND PARTICIPANTS: Applying individual-level nationwide register information on
      socio-demographics, dispensed prescription drugs and hospital discharges, all
      Danish citizens aged 20+ without previous register-markers of CVD, diabetes or
      statin therapy were followed during 2002-2006 for first occurrence of myocardial
      infarction (MI) and a dispensed statin prescription (N = 3.3 mill). MAIN OUTCOME
      MEASURES: Stratified by gender, 5-year age-groups and socioeconomic position
      (SEP), incidence of MI was applied as a proxy for statin need. Need-standardized
      statin incidence rates were calculated, applying MI incidence rate ratios (IRR)
      as need-weights to adjust for unequal needs across SEP.Horizontal equity in
      initiating statin therapy was tested by means of Poisson regression analysis.
      Applying the need-standardized statin parameters and the lowest SEP-group as
      reference, a need-standardized statin IRR > 1 translates into horizontal inequity
      favouring the higher SEP-groups. RESULTS: MI incidence decreased with increasing
      SEP without a parallel trend in incidence of statin therapy. According to the
      regression analyses, the need-standardized statin incidence increased in men aged
      40-64 by 17%, IRR 1.17 (95% CI: 1.14-1.19) with each increase in income quintile.
      In women the proportion was 23%, IRR 1.23 (1.16-1.29). An analogous pattern was
      seen applying education as SEP indicator and among subjects aged 65-84.
      CONCLUSION: The high-risk strategy to prevent CVD by initiating statin therapy
      seems to be inequitable, reaching primarily high-risk subjects in lower risk SEP
      groups.

PMID- 22863327
TI  - Chronic venous leg ulcers: the future of cell-based therapies.

PMID- 22863328
TI  - Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes
      for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double
      blind, randomised, placebo-controlled trial.
AB  - BACKGROUND: Many patients with venous leg ulcers do not heal with standard care.
      HP802-247 is a novel spray-applied cell therapy containing growth-arrested
      allogeneic neonatal keratinocytes and fibroblasts. We compared different cell
      concentrations and dosing frequencies of HP802-247 for benefit and harm when
      applied to chronic venous leg ulcers. METHODS: We enrolled adult outpatients from
      28 centres in the USA and Canada with up to three ulcers, venous reflux confirmed
      by doppler ultrasonography, and adequate arterial flow in this phase 2, double
      blind, randomised, placebo-controlled trial if at least one ulcer measured 2-12
      cm(2) in area and had persisted for 6-104 weeks. Patients were randomly assigned
      by computer-generated block randomisation in a 1:1:1:1:1 ratio to 5.0*10(6) cells
      per mL every 7 days or every 14 days, or 0.5*10(6) cells per mL every 7 days or
      every 14 days, or to vehicle alone every 7 days. All five groups received four
      layer compression bandages. The trial sponsor, trial monitors, statisticians,
      investigators, centre personnel, and patients were masked to treatment
      allocation. The primary endpoint was mean percentage change in wound area at the
      end of 12 weeks. Analyses were by intention to treat, excluding one patient who
      died of unrelated causes before first treatment. This trial is registered with
      ClinicalTrials.gov NCT00852995. FINDINGS: 45 patients were assigned to 5.0*10(6)
      cells per mL every 7 days, 44 to 5.0*10(6) cells per mL every 14 days, 43 to 0.5
      *10(6) cells per mL every 7 days, 46 to 0.5 *10(6) cells per mL every 14 days,
      and 50 to vehicle alone. All required visits were completed by 205 patients. The
      primary outcome analysis showed significantly greater mean reduction in wound
      area associated with active treatment compared with vehicle (p=0.0446), with the
      dose of 0.5 *10(6) cells/mL every 14 days showing the largest improvement
      compared with vehicle (15.98%, 95% CI 5.56-26.41, p=0.0028). Adverse events were
      much the same across all groups, with only new skin ulcers and cellulitis
      occurring in more than 5% of patients. INTERPRETATION: Venous leg ulcers can be
      healed with a spray formulation of allogeneic neonatal keratinocytes and
      fibroblasts without the need for tissue engineering, at an optimum dose of
      0.5*10(6) cells per mL every 14 days. FUNDING: Healthpoint Biotherapeutics.

PMID- 22863330
TI  - Preoperative and postoperative comparisons of navigation and radiologic limb
      alignment measurements after high tibial osteotomy.
AB  - PURPOSE: To determine whether navigation-assisted intraoperative lower limb
      alignment in open wedge high tibial osteotomy (HTO) correlates with preoperative
      and postoperative radiographic alignment. METHODS: This prospective study
      involved 35 patients (39 knees) who underwent navigation HTO for primary medial
      osteoarthritis. The mechanical axis (MA) and weight-bearing line (WBL) ratio were
      calculated from preoperative radiographs, intraoperative navigation, and
      postoperative (6 months) radiographs. Reliability between navigation and
      radiographic alignment was analyzed by use of intraclass correlation coefficients
      (ICCs) with thresholds as follows: good, greater than 0.75; fair, 0.4 to 0.75;
      and poor, less than 0.4. The surgical target for the MA was a final valgus
      overcorrection of 2 degrees  to 8 degrees , and the WBL ratio target was between
      50% and 70%. Outliers for differences between intraoperative navigation and
      postoperative radiographic results were defined as greater than +/-3 degrees  for
      the MA and greater than +/-10% for the WBL ratio. RESULTS: The MA target was
      achieved in 33 of 39 knees (84.6%), and the WBL ratio target was achieved in 30
      of 39 knees (74.4%). ICCs for navigational reliability were good for preoperative
      MA and WBL ratio and fair for postoperative MA and WBL ratio. The ICCs for the MA
      were better than those for the WBL ratio for both preoperative and postoperative
      measurements. The differences between the number of outliers between the
      navigation and radiographic MA and WBL were greater postoperatively than
      preoperatively. In addition, the postoperative differences in the extent of the
      outliers between navigation and radiographic measurements were greater for WBL
      ratios than the MA (P = .023). CONCLUSIONS: This study found that use of a
      navigation system achieved the target value for MA lower limb correction in over
      80% of open wedge HTO cases, using radiographic data as the gold standard for
      alignment. Because the navigational measurements of lower limbs during open wedge
      HTO did not correlate with postoperative radiographic alignment, corrections
      should not be based solely on navigational results. In assessing the reliability
      of navigational open wedge HTO for correction of lower limb alignment, the MA is
      a better radiologic parameter than the WBL ratio. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 22863329
TI  - Control and inhibition analysis of complex formation processes.
AB  - BACKGROUND: Proteolytic degradation of the extracellular matrix (ECM) is a key
      event in tumour metastasis and invasion. Matrix metalloproteinases (MMPs) are a
      family of endopeptidases that degrade most of the components of the ECM. Several
      broad-spectrum MMP inhibitors (MMPIs) have been developed, but have had little
      success due to side effects. Thus, it is important to develop mathematical
      methods to provide new drug treatment strategies. Matrix metalloproteinase 2
      (MMP2) activation occurs via a mechanism involving complex formation that
      consists of membrane type 1 MMP (MT1-MMP), tissue inhibitor of matrix
      metalloproteinase 2 (TIMP2) and MMP2. Here, we focus on developing a method for
      analysing the complex formation process. RESULTS: We used control analysis to
      investigate inhibitor responses in complex formation processes. The essence of
      the analysis is to define the response coefficient which measures the inhibitory
      efficiency, a small fractional change of concentration of a targeting molecule in
      response to a small fractional change of concentration of an inhibitor. First, by
      using the response coefficient, we investigated models for general classes of
      complex formation processes: chain reaction systems composed of ordered steps,
      and chain reaction systems and site-binding reaction systems composed of
      unordered multi-branched steps. By analysing the ordered step models, we showed
      that parameter-independent inequalities between the response coefficients held.
      For the unordered multi-branched step models, we showed that independence of the
      response coefficients with respect to equilibrium constants held. As an
      application of our analysis, we discuss a mathematical model for the MMP2
      activation process. By putting the experimentally derived parameter values into
      the model, we were able to conclude that the TIMP2 and MMP2 interaction is the
      most efficient interaction to consider in selecting inhibitors. CONCLUSIONS: Our
      result identifies a new drug target in the process of the MMP2 activation. Thus,
      our analysis will provide new insight into the design of more efficient drug
      strategies for cancer treatment.

PMID- 22863331
TI  - Remaking surgical socialization: work hour restrictions, rites of passage, and
      occupational identity.
AB  - We examine how a policy aimed at improving patient safety by limiting residents'
      work hours brought with it an unintended and unexamined consequence: altered
      socialization due to modified rites of passage during residency that endangered
      the stereotypical "Surgical Personality" and created a potential rift between the
      occupational identities of surgical residents who train under duty hour
      regulations and those who trained before they were imposed. Through participant
      observation occurring between June 2008 and June 2010, in-depth interviews (n =
      13), and focus groups (n = 2), we explore how surgical residents training in four
      U.S. hospitals think about the threats that the shift from unrestricted to
      restricted duty hours creates for their claims of competence and professionalism.
      We identify three types of resident responses: (1) neutralizing statements that
      deny any significant change to occupational identity has occurred; (2) embracing
      statements that express the belief that a changed and more balanced occupational
      identity is needed; and (3) apprehensive statements that expressed fear of an
      altered occupational identity and an anxiety about readiness for individual
      practice.

PMID- 22863332
TI  - Characteristics of early vocabulary and grammar development in Slovenian-speaking
      infants and toddlers: a CDI-adaptation study*.
AB  - A large body of research shows that vocabulary does not develop independently of
      grammar, representing a better predictor of the grammatical complexity of
      toddlers' utterances than age. This study examines for the first time the
      characteristics of vocabulary and grammar development in Slovenian-speaking
      infants and toddlers using the Slovenian adaptation of the MacArthur-Bates
      Communicative Development Inventories (CDI). The sample included 512 Slovenian
      speaking infants and toddlers aged 0 ; 8 to 2 ; 6. The findings suggest that
      between age 0 ; 8 and 2 ; 6 the development of vocabulary is best described using
      a quadratic function. The results also show that nouns predominate in the
      vocabularies of infants and toddlers of various ages; as they age and with the
      increasing size of their vocabularies, the share of interjections decreases and
      the share of verbs and adjectives increases. The size of vocabulary was also
      found to be related to the grammatical structure of toddlers' utterances.

PMID- 22863333
TI  - Obesity, lifestyle risk-factors, and health service outcomes among healthy middle
      aged adults in Canada.
AB  - BACKGROUND: The extent to which uncomplicated obesity among an otherwise healthy
      middle-aged population is associated with higher longitudinal health-care
      expenditures remains unclear. METHODS: To examine the incremental long-term
      health service expenditures and outcomes associated with uncomplicated obesity,
      9398 participants of the 1994-1996 National Population Health Survey were linked
      to administrative data and followed longitudinally forward for 11.5 years to
      track health service utilization costs and death. Patients with pre-existing
      heart disease, those who were 65 years of age and older, and those with self
      reported body mass indexes of <18.5 kg/m2 at inception were excluded. Propensity
      matching was used to compare obesity (+/- other baseline risk-factors and
      lifestyle behaviours) with normal-weight healthy controls. Cost-analyses were
      conducted from the perspective of Ontario's publicly-funded health care system.
      RESULTS: Obesity as an isolated risk-factor was not associated with significantly
      higher health-care costs as compared with normal weight matched controls
      (Canadian $8,294.67 vs. Canadian $7,323.59, P = 0.27). However, obesity in
      combination with other lifestyle factors was associated with significantly higher
      cumulative expenditures as compared with normal-weight healthy matched controls
      (CAD$14,186.81 for those with obesity + 3 additional risk-factors vs.
      CAD$7,029.87 for those with normal BMI and no other risk-factors, P < 0.001). The
      likelihood that obese individuals developed future diabetes and hypertension also
      rose markedly when other lifestyle factors, such as smoking, physical inactivity
      and/or psychosocial distress were present at baseline. CONCLUSIONS: The
      incremental health-care costs associated with obesity was modest in isolation,
      but increased significantly when combined with other lifestyle risk-factors. Such
      findings have relevance to the selection, prioritization, and cost-effective
      targeting of therapeutic lifestyle interventions.

PMID- 22863335
TI  - Meta-analysis comparing total hip arthroplasty with hemiarthroplasty in the
      treatment of displaced femoral neck fractures in patients over 70 years old.
AB  - OBJECTIVE: Total hip arthroplasty (THA) and hemiarthroplasty (HA) are effective
      methods currently used to treat femoral neck fracture in elderly patients, but
      the two options remain controversial in patients over 70 years old. The main
      purpose of our study was to determine whether THA or HA is a superior treatment
      of femoral fractures involving a displaced neck in patients who are over 70 years
      of age. METHODS: A computer-based online search of Medline (1970-2011), PubMed
      (1977-2011), and the Cochrane Central Register of Controlled Trials (2002-2011)
      was conducted. Six relevant randomized controlled trials with a total of 739
      patients were included for the final analysis. The analysis was performed with
      software RevMan 5.0. RESULTS: We found that compared with THA, HA needed shorter
      average time and lost less blood. While over the long-term follow-up, THA
      patients exhibited significantly less pain and better function and were less
      likely to require a revision hip surgery. Postoperative infection was equally
      common among HA and THA patients. CONCLUSIONS: The significant differences in
      outcomes suggest that THA is a valuable treatment option for active elderly hip
      fracture individuals. However, patients who are older, impaired or
      institutionalized benefit from HA.

PMID- 22863334
TI  - Transient Nod factor-dependent gene expression in the nodulation-competent zone
      of soybean (Glycine max [L.] Merr.) roots.
AB  - All lateral organ development in plants, such as nodulation in legumes, requires
      the temporal and spatial regulation of genes and gene networks. A total mRNA
      profiling approach using RNA-seq to target the specific soybean (Glycine max)
      root tissues responding to compatible rhizobia [i.e. the Zone Of Nodulation
      (ZON)] revealed a large number of novel, often transient, mRNA changes occurring
      during the early stages of nodulation. Focusing on the ZON enabled us to discard
      the majority of root tissues and their developmentally diverse gene transcripts,
      thereby highlighting the lowly and transiently expressed nodulation-specific
      genes. It also enabled us to concentrate on a precise moment in early nodule
      development at each sampling time. We focused on discovering genes regulated
      specifically by the Bradyrhizobium-produced Nod factor signal, by inoculating
      roots with either a competent wild-type or incompetent mutant (nodC(-) ) strain
      of Bradyrhizobium japonicum. Collectively, 2915 genes were identified as being
      differentially expressed, including many known soybean nodulation genes. A number
      of unknown nodulation gene candidates and soybean orthologues of nodulation genes
      previously reported in other legume species were also identified. The
      differential expression of several candidates was confirmed and further
      characterized via inoculation time-course studies and qRT-PCR. The expression of
      many genes, including an endo-1,4-beta-glucanase, a cytochrome P450 and a TIR-LRR
      NBS receptor kinase, was transient, peaking quickly during the initiation of
      nodule ontogeny. Additional genes were found to be down-regulated. Significantly,
      a set of differentially regulated genes acting in the gibberellic acid (GA)
      biosynthesis pathway was discovered, suggesting a novel role of GAs in
      nodulation.

PMID- 22863336
TI  - Outcome of surgical treatment of type IV capitellum fractures in adults.
AB  - OBJECTIVE: Fractures of the capitellum and trochlea constitute less than 1% of
      all elbow fractures and a shear fracture involving the capitellum and extending
      medially into most of the trochlea is rarely reported. Type IV capitellum
      fracture is still controversial in regard to its radiographic appearance,
      surgical approach and osteosynthesis. We report 10 cases of type IV capitellum
      fracture with a view to elucidating its clinical features and treatment outcome.
      METHODS: We treated 10 patients of type IV capitellum fracture with a mean age of
      32 years. A uniform surgical approach and postoperative rehabilitation were
      followed. RESULTS: Nine patients presented to us after a mean of 4 days of injury
      and one patient was nonunion after 6 months of injury who had been treated
      conservatively by a bone setter. Double arc sign was absent in 6 cases.
      Intraoperatively 6 capitellotrochlear fragments were devoid of soft tissue
      attachments. By Mayo Elbow Performance Score evaluation, 7 patients got
      excellent, 2 good and 1 fair results. One patient with associated elbow
      dislocation developed heterotopic ossification. There was no case of avascular
      necrosis, osteoarthrosis or fixation failures. CONCLUSIONS: Type IV capitellum
      fractures are rare and belong to complex articular injuries. A good functional
      outcome can only be achieved with open reduction and stable internal fixation
      followed by early mobilization. Preoperative radiographic assessment and computed
      tomography help surgeons in choosing the right surgical approach and implants.
      Good surgical technique and stable internal fixation are the keys to early
      mobilization and good functional outcome.

PMID- 22863337
TI  - Soft tissue distraction using pentagonal frame for long-standing traumatic
      flexion deformity of interphalangeal joints.
AB  - OBJECTIVE: Interphalangeal joint contracture is a challenging complication of
      hand trauma, which reduces the functional capacity of the entire hand. In this
      study we evaluated the results of soft tissue distraction with no collateral
      ligament transection or volar plate removal in comparison with traditional
      operation of contracture release and partial ligament transection and volar plate
      removal. METHODS: In this prospective study, a total of 40 patients in two equal
      groups (A and B) were studied. Patients suffering from chronic flexion
      contracture of abrasive traumatic nature were included. Group A were treated by
      soft tissue distraction using pentagonal frame technique and in Group B the
      contracture release was followed by finger splinting. RESULTS: Analyzed data
      revealed a significant difference between the two groups for range of motion in
      the proximal interphalangeal joints (P less than 0.05), while it was not
      meaningful in the distal interphalangeal joints (P larger than 0.05). There was
      not a significant difference in the degrees of flexion contracture between groups
      (P larger than 0.05). Regression analysis showed that using pentagonal frame
      technique significantly increased the mean improvement in range of motion of
      proximal interphalangeal joints (P less than 0.001), while the higher the
      preoperative flexion contracture was observed in proximal interphalangeal joints,
      the lower improvement was achieved in range of motion of proximal interphalangeal
      joints after intervention (P less than 0.001). CONCLUSION: Soft tissue
      distraction using pentagonal frame technique with gradual and continuous
      collateral ligament and surrounding joint tissues distraction combined with skin
      Z-plasty significantly improves the range of motion in patients with chronic
      traumatic flexion deformity of proximal and/or distal interphalangeal joints.

PMID- 22863338
TI  - Antibiotic-loaded articulating cement spacers in two-stage revision for infected
      total knee arthroplasty: individual antibiotic treatment and early results of 21
      cases.
AB  - OBJECTIVE: To detail our early experience and technique of a modified two-stage
      reimplantation protocol using antibiotic-loaded articulating cement spacers
      (ALACSs) for treatment of late periprosthetic infection after total knee
      arthroplasty (TKA). METHODS: From January 2006 to February 2009, a series of 21
      patients (21 knees) with late infected TKAs were treated by radical debridement
      and removal of all components and cement, and then articulating spacers were
      implanted using antibiotic-impregnated bone cement. For this purpose, 4 g
      vancomycin powder was mixed with per 40 g cement. Graduated knee motion and
      partial weight bearing activity were encouraged in the interval period. Each
      patient received an individual systemic organism-sensitive antimicrobial therapy
      for 4.9 (range, 2-8) weeks followed by a second-stage TKA revision. All the
      patients were regularly followed up using the American Knee Society Scoring
      System. RESULTS: Each case underwent a successful two-stage exchange and had
      infection eradicated, none had recurrent infection after an average of 32.2
      (range, 17-54) months of follow-up. Preoperatively, the mean knee score was 53.5 
      points, function score was 27.3 points, pain score was 25.7 points, range of
      motion (ROM) was 82.0 degree extensor lag was 2 degree Between stages, the mean
      knee score was increased to 61.3 points, function score to 45 points, pain score
      to 35 points, ROM to 88.2 degree and extensor lag to 3.4 degree At final follow
      up, the mean knee score was further increased to 82.1 points, function score to
      74.5 points, pain score to 42.1 points, ROM to 94.3 degree and knee extension lag
      to 1.9 degree The interval period was 11.5 (range, 6-32) weeks. The amount of
      bone loss was unchanged between stages. No patient developed noticeable
      dysfunction of the liver or kidney or other complications such as impaired wound
      healing, deep venous thrombosis, pulmonary embolism, cerebrovascular accidents,
      etc. CONCLUSIONS: Treating infected TKA with ALACS avoids spacer-related bone
      loss, preserves knee function between stages, and eradicates infection
      effectively without significant complications. The early clinical results are
      inspiring. The authors believe that radical and repeated (if needed) debridement,
      individual application of systemic antibiotics, and reasonable timing judgement
      upon the secondary revision are all key factors related to a successful outcome
      with two-stage reimplantation procedure for infected TKA.

PMID- 22863339
TI  - Fatal motorcycle accidents in Fars Province, Iran: a community-based survey.
AB  - OBJECTIVE: To identify the main characteristics of victims of motorcycle
      accidents in Fars Province, Iran. METHODS: This cross-sectional study was
      conducted in Fars Province which has the fourth largest population of all 31
      provinces in Iran from March 2009 to June 2010. We included data from all 542
      recorded cases of fatalities due to motor vehicle accidents. Data were recorded
      from the forensic medicine registry consisting of demographic and accident
      related information. Demographic information consisted of name, age, sex, status
      of fatal victim (motorcycle driver vs passenger) and educational level. RESULTS:
      Of the 2 345 autopsy records from the forensic medicine archives, 542 (23.1%)
      gave the cause of death as motor vehicle accidents. Mean age of these victims was
      (31.4+/-6.5) years, and the male to female ratio was 28. Head injury was the most
      common cause of death in these victims, and overall they tended to have a low
      level of education. Motorcycle accidents frequently involved younger age groups
      (15-35 years), and head trauma related with non-use of a helmet was the most
      common cause of death. CONCLUSIONS: Head injury is frequent among victims in the
      province we studied. This situation may be related to the victims' low
      socioeconomic status and little education regarding traffic laws leading to
      speeding and disregard of these laws along with their weak enforcement.

PMID- 22863340
TI  - Large bone-flap decompressive craniotomy for treatment of serious craniocerebral
      injury associated with cerebral infarction.
AB  - OBJECTIVE: To elucidate the therapeutic effect of subtemporal decompressive
      craniotomy with large flap resection on serious craniocerebral injury associated
      with cerebral infarction. METHODS: Forty-eight cases of serious head injury
      accompanied by cerebral infarction were classified into two groups with each
      having 24 cases: treatment group, in which large bone-flap decompressive
      craniotomy was performed; control group, in which routine craniotomy and hematoma
      evacuation were adopted. The status of cerebral infarction pre- and post
      operation, as well as the curative effect 3 months after operation were
      comparatively analysed between the two groups. RESULTS: There was no significant
      difference regarding the status of cerebral infarction on the first day after
      operation; while one week after operation, the size of cerebral infarction was
      significantly smaller in treatment group than control one (P less than 0.05).
      Postoperative 3 months, the mortality rate was 20.8% in treatment group, being
      evidently superior to that of control group (33.3%, P less than 0.05). The mo-
      derate disability (good and fair) rate was 41.7% in treatment group,
      significantly higher than that in control group (25.0%, P less than 0.05).
      CONCLUSION: Large bone-flap decompressive craniotomy is confirmed effective and
      hence it offers us a preferable alternative of treatment by which to reduce
      disability and fatality rates for patients with serious head injury accompanied
      by cerebral infarction.

PMID- 22863341
TI  - A new technique for insertion of barrel plate over dynamic hip/compression lag
      screw: a case report.
AB  - Dynamic hip/compression screw (DHS/DCS) is one of the most commonly performed
      surgeries in orthopaedic practice. Sliding barrel plate over the DHS/DCS lag
      screw is one of the very crucial and at times uncomfor-table and time consuming
      steps of DHS/DCS surgery especially when it comes to inexperienced surgeons and
      residents. Also in developing countries where not all standard instrumentation is
      always available, this crucial step becomes more time consuming. Here we present
      a case report of 58-year-old male patient with intertrochanteric fracture, in
      which we used a new device for insertion of barrel plate over DHS/DCS lag screw
      and found that a small DHS/DCS lag screw extension (sliding jig of barrel plate)
      can be very helpful to slide barrel plate over the DHS/DCS lag screw.

PMID- 22863342
TI  - Management of hemodynamically unstable pelvic fracture in pregnancy: a case
      report and review of literature.
AB  - We present an unusual case of an unstable pelvic fracture during pregnancy
      period, who suffered fetal death and splenic rupture simultaneously which
      developed massive delayed hemorrhage in abdomen. When considering potential
      causes of fetal death, direct trauma to the uterus, placenta, or fetus was not
      associated with a higher fetal mortality rate, compared with maternal hemorrhage.
      A cesarean section and splenectomy could rescue the maternal life from the
      hemorrhage situation. Successful treatment of these rare cases is possible with
      careful pre-, peri-, and post-operative evaluation of the mother and fetus by a
      multidisciplinary team.

PMID- 22863343
TI  - Buttress plating for a rare case of comminuted medial condylar Hoffa fracture
      associated with patellar fracture.
AB  - Hoffa fracture is an uncommon injury. In the literature, lateral condylar Hoffa
      fracture is mentioned as a more common injury pattern than medial condylar Hoffa
      fracture. The mechanism of injury and method of treatment is not very well
      described in the literature. We are presenting a rare case of comminuted medial
      condylar Hoffa fracture with ipsilateral patellar fracture. The mechanism of
      injury has not been described in the literature. Lag screw fixation, which is the
      most acceptable method of treatment, is not possible due to comminution. We
      explain the possible mechanism of injury and fix the fracture with L-buttress
      plate.

PMID- 22863344
TI  - Abscess formation in vertebral canal and presacral area following penetrating
      injury of rectum and sacral vertebra by a steel rod.
AB  - Penetrating injury to the rectum, vertebral body and spinal cord by a steel rod
      is a rare condition. Treatment of this kind of injury is very challenging. Rectal
      injury requires repair and fecal diversion, while debridement of the spine is
      difficult, especially when the injury site is very long. Here we report a case of
      penetrating injury of rectum and sacral vertebra by a steel rod after falling
      onto the ground from 1 m height. The abscess cavity was irrigated with 3%
      hydrogen peroxide and physio-logical saline repeatedly. The bony canal was
      carefully debrided, curetted and bony fragments were removed. Spinal irrigation
      and drainage lasted for 2 months and sensitive antibiotic (amikacin sulfate) was
      given 7 days after surgery, but abscess was still formed in the vertebral canal.
      At 6-month follow-up, the patient was paralyzed without any neurological
      improvement, and the pain in low back and lower limb still continued.

PMID- 22863345
TI  - Axillary artery thrombosis with anteroinferior shoulder dislocation: a rare case
      report and review of literature.
AB  - A very rare and serious complication of shoulder dislocation is a lesion to the
      axillary artery in the elderly population, whose vascular structures have become
      less flexible. Axillary artery injury secondary to anteroinferior shoulder
      dislocation is much rarer, especially in the young people. Proper recognition and
      treatment of this entity offers a full recovery to the patient. Present report
      highlights the possibility of axillary artery injury with anteroinferior shoulder
      dislocation. A few case reports and small case series of this injury have been
      reviewed. And recommendations for management have been brought up to date, in
      line with current thinking.

PMID- 22863346
TI  - Anterior dislocation of shoulder in eclampsia: a case report.
AB  - This case report presents a 25-year-old female patient with anterior dislocation
      of right shoulder secondary to seizures as a complication of eclampsia. This is
      an unusual mechanism of injury, but similar to other uncontrolled muscular
      contractions caused by electroconvulsive therapy, etc. To the best of our
      knowledge only one such case has been reported in the English literature. Closed
      reduction under general anaesthesia was successfully achieved. High suspicion in
      patients complaining of pain over shoulder joint is necessary for early diagnosis
      of this condition.

PMID- 22863347
TI  - Spontaneous atraumatic dislocation of sternoclavicular joint in Reiter syndrome.
AB  - Reactive arthritis or Reiter's syndrome characteristically affects the joint of
      the lower limb in an asymmetrical pattern. Usually it does not affect the axial
      skeleton or upper limbs. Although cases of atraumatic atlantoaxial subluxations
      have been reported, no case of spontaneous sternoclavicular dislocation in
      Reiter's syndrome has been reported. This paper describes a case of a 26 year old
      male patient who developed a spontaneous posterior sternoclavicular joint
      dislocation. No attempt of reduction was made and the patient was managed
      conservatively with good results.

PMID- 22863348
TI  - Ligamentotaxis for comminuted fracture of capitate: a case report.
AB  - We present the technical report for treatment of comminuted fracture of the
      capitate with ligamentotaxis. The base of third metacarpal was found to be
      fractured with comminution of the capitate. The decrease in carpal height index
      and comminution of the third metacarpal base lead to dilemma between conservative
      treatment and surgical management of this particular injury. The surgical
      management was chosen to maintain the carpal height index of the wrist to prevent
      the late degenerative changes.The patient was applied with external fixator in
      distraction mode expanning the wrist joint for six weeks, and the wrist was
      mobilised after removal of the fixator. It is shown that the external fixator in
      distraction mode expanning the wrist joint is a good alternative method for
      treatment of capitate fracture.

PMID- 22863349
TI  - Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort
      attending a specialist nephrology out-patient clinic.
AB  - BACKGROUND: ADPKD affects approximately 1:1000 of the worldwide population. It is
      caused by mutations in two genes, PKD1 and PKD2. Although allelic variation has
      some influence on disease severity, genic effects are strong, with PKD2 mutations
      predicting later onset of ESRF by up to 20 years. We therefore screened a cohort
      of ADPKD patients attending a nephrology out-patient clinic for PKD2 mutations,
      to identify factors that can be used to offer targeted gene testing and to
      provide patients with improved prognostic information. METHODS: 142 consecutive
      individuals presenting to a hospital nephrology out-patient service with a
      diagnosis of ADPKD and CKD stage 4 or less were screened for mutations in PKD2,
      following clinical evaluation and provision of a detailed family history (FH).
      RESULTS: PKD2 mutations were identified in one fifth of cases. 12% of non-PKD2
      patients progressed to ESRF during this study whilst none with a PKD2 mutation
      did (median 38.5 months of follow-up, range 16-88 months, p < 0.03). A
      significant difference was found in age at ESRF of affected family members (non
      PKD2 vs. PKD2, 54 yrs vs. 65 yrs; p < 0.0001). No PKD2 mutations were identified
      in patients with a FH of ESRF occurring before age 50 yrs, whereas a PKD2
      mutation was predicted by a positive FH without ESRF. CONCLUSIONS: PKD2 testing
      has a clinically significant detection rate in the pre-ESRF population. It did
      not accurately distinguish those individuals with milder renal disease defined by
      stage of CKD but did identify a group less likely to progress to ESRF. When used
      with detailed FH, it offers useful prognostic information for individuals and
      their families. It can therefore be offered to all but those whose relatives have
      developed ESRF before age 50.

PMID- 22863350
TI  - Threats to macroalgal coralligenous assemblages in the Mediterranean Sea.
AB  - Coralligenous habitat is one of the most important coastal systems of the
      Mediterranean Sea. This paper evaluates the main threats to macroalgal
      coralligenous habitats through a review of the relevant literature.
      Sedimentation, nutrient enrichment and biological invasions can cause severe
      alterations in the structure of coralligenous assemblages due to the regression
      of perennial structuring species and increases in populations of ephemeral algae.
      Under pristine conditions, mechanical disturbance seems to be easily mitigated by
      the recovery capability of coralligenous assemblages; however, such disturbances
      seriously affect coralligenous structure if they occur in concert with other
      stressors. Important synergetic effects among all the studied anthropogenic
      disturbances are also highlighted. The main consequences of the considered
      stressors are the loss of the complexity of macroalgal assemblages and the
      deterioration of both alpha and beta diversity.

PMID- 22863351
TI  - Assessing, managing and monitoring contaminated aquatic sediments.
AB  - Contaminated sediments continue to be a global problem that is too often not
      addressed in a logical, tiered framework. Such frameworks, when they exist,
      typically are restricted to assessment and prioritization and do not include
      possible remedies with accompanying follow-up monitoring to ensure those remedies
      were successful and further remedies are not necessary. A logical, tiered
      framework that encompasses all of the above (i.e., assessment through to post
      remedy monitoring) is described. This framework was developed by the Canadian
      Government for use in Canada but has wider applications.

PMID- 22863352
TI  - Baseline concentration of 210Po in Kuwait's commercial fish species.
AB  - This baseline study highlights the (210)Po variation in whole fishes with
      different feeding habits. Whole-body (210)Po concentrations were determined in
      ten important commercial fish species found in the northern Arabian Gulf to serve
      as baseline data. Primarily, (210)Po is absorbed from water, concentrated by
      phytoplankton and microzooplankton, and then transferred to the next trophic
      level along the marine food chain. The lowest concentration of (210)Po was
      measured in larger carnivorous fishes like hamoor (0.089 Bq kg(-1)), while the
      highest was found in the fishes that feed on algae, zooplanktons and detritus,
      like battan (3.30 Bq kg(-1)). The baseline data can be used to understand both
      the trophic transfer of (210)Po in the marine food chain and the (210)Po
      concentration factors in fish from the Arabian Gulf.

PMID- 22863353
TI  - Papuan Bird's Head Seascape: emerging threats and challenges in the global center
      of marine biodiversity.
AB  - The Bird's Head Seascape located in eastern Indonesia is the global epicenter of
      tropical shallow water marine biodiversity with over 600 species of corals and
      1,638 species of coral reef fishes. The Seascape also includes critical habitats
      for globally threatened marine species, including sea turtles and cetaceans.
      Since 2001, the region has undergone rapid development in fisheries, oil and gas
      extraction, mining and logging. The expansion of these sectors, combined with
      illegal activities and poorly planned coastal development, is accelerating
      deterioration of coastal and marine environments. At the same time, regency
      governments have expanded their marine protected area networks to cover 3,594,702
      ha of islands and coastal waters. Low population numbers, relatively healthy
      natural resources and a strong tenure system in eastern Indonesia provide an
      opportunity for government and local communities to collaboratively manage their
      resources sustainably to ensure long-term food security, while meeting their
      development aspirations.

PMID- 22863354
TI  - Schwann cells migrate along axons in the absence of GDNF signaling.
AB  - BACKGROUND: During development neural crest derived Schwann Cell (SC) precursors
      migrate to nerve trunks and populate nascent nerves. Axonal ensheathment by SC is
      a prerequisite for normal nerve function and the integrity of myelinated as well
      as nonmyelinated axons. To provide adequate support functions, SC colonize entire
      nerves. One important prerequisite for this is their migration into distal axonal
      regions. RESULTS: Here, we studied the role of Glial cell line derived
      neurotrophic factor (GDNF), a TGF-beta related growth factor, for SC migration.
      To this end we used a superior cervical ganglion (SCG) explant-SC migration
      assay, GDNF null mutant mouse embryos and a chemical inhibitor for GDNF signaling
      in combination with time-lapse imaging. We found that GDNF signaling is
      dispensable for SC migration along murine embryonic sympathetic axons.
      Furthermore, in vivo analyzes revealed that SC migration along the sciatic nerve
      is also not dependent on GDNF. CONCLUSIONS: In contrast to previous in vitro
      findings in the sciatic nerve and a SC precursor cell line, our results clearly
      indicate that GDNF is dispensable for embryonic SC migration. This is
      demonstrated for the sympathetic nervous system and also for the sciatic nerve in
      mouse.

PMID- 22863356
TI  - Vitreoretinal interface in central serous choroidopathy: a retrospective case
      control study.
AB  - PURPOSE: To investigate the frequency and patterns of vitreoretinal adherence in
      central serous choroidopathy (CSC) using spectral domain optical coherence
      tomography (SD-OCT) imaging and compare them with normal subject. METHODS: A
      descriptive observational analytical retrospective case-control study. The study
      patients were split into non-chronic and chronic CSC groups and compared with an
      age- and gender-matched control group composed of healthy individuals without
      CSC. Five patterns of vitreoretinal adherence were defined: lacunae, partial
      posterior vitreous detachment (partial-PVD), epiretinal membrane (ERM), focal
      vitreomacular adherence (VMA) and no recognizable pattern. Statistical analysis
      was performed. RESULTS: One hundred and four eyes of 52 patients were included in
      this study. Forty-eight eyes of 24 patients had chronic CSC and 56 eyes of 28
      patients had non-chronic CSC. The control group for chronic CSC included 96
      normal eyes of 48 subjects, and the control group for non-chronic CSC included
      one hundred and twelve normal eyes of 56 subjects. We found a recognizable
      pattern of the vitreoretinal interface (lacuna, partial-PPV, VMA or ERM) more
      often in non-chronic CSC (p = 0.0001, OR = 6.51 and CI = 2.71-15.62) and in
      chronic CSC patients (p = 0.001, OR = 4.05, CI: 1.77-9.57) than in normal
      subjects. CONCLUSION: The proportion of patterns of vitreoretinal adherence and
      interface found in CSC changes with age and manifests differently compared with
      normal eyes. The results indicate early changes in CSC patients younger than 40
      years of old bilaterally.

PMID- 22863355
TI  - Extended thromboprophylaxis for medically ill patients with decreased mobility:
      does it improve outcomes?
AB  - BACKGROUND: Duration of thromboprophylaxis beyond hospital discharge for
      medically ill patients has been controversial. Therefore an evaluation was made
      of the evidence currently available. METHODS: A search was made of the Pub Med,
      CENTRAL and EMBASE databases for randomized controlled trials from 1966 through
      to 2011. Interventions included thromboprophylaxis administered over an extended
      period in patients hospitalized for acute medical illness with decreased level of
      mobility. No differentiation was made for the medication used for individual
      studies. The comparator included standard medical therapy and/or placebo. The
      efficacy outcomes assessed were a composite of asymptomatic and symptomatic deep
      vein thromboses (DVT), pulmonary emboli (PE) and venous thromboembolism (VTE)
      related deaths in the intervention group vs. the comparator group, as well as the
      safety outcomes evaluated with rates of bleeding events at the end of at least 30
      days of follow-up. The methodological quality of the studies was assessed, as was
      publication bias. Event rates were compared using a forest plot of relative risk
      (RR; 95% confidence interval (CI)) using a random effects model (Mantel-Haenszel)
      between the active thromboprophylaxis and controls. Statistical analysis was
      carried out with Review Manager V5.1. RESULTS: Three recent studies were
      included. Extended duration thromboprophylaxis reduced the combined composite
      event rate, RR 0.75 (0.64, 0.88). However, individual clinical endpoints were not
      significantly improved with extended prophylaxis: asymptomatic proximal DVT, RR
      0.85 (0.68, 1.05); symptomatic DVT, RR 0.44 (0.19, 1.00); symptomatic non-fatal
      PE, RR 0.80 (0.43, 1.48); VTE-related death, RR 0.64 (0.38, 1.10). However,
      bleeding events were far more prevalent with extended thromboprophylaxis with
      major bleeds, RR 2.68 (1.78, 4.05), with a number needed to harm of 194.
      CONCLUSION: Currently available evidence does not indicate that routine
      administration of post-discharge prophylaxis will be beneficial to the patients
      admitted for medical illness.

PMID- 22863357
TI  - Requirement of lid2 for interfacial activation of a family I.3 lipase with unique
      two lid structures.
AB  - A family I.3 lipase from Pseudomonas sp. MIS38 (PML) is characterized by the
      presence of two lids (lid1 and lid2) that greatly change conformation upon
      substrate binding. While lid1 represents the commonly known lid in lipases, lid2
      is unique to PML and other family I.3 lipases. To clarify the role of lid2 in
      PML, a lid2 deletion mutant (DeltaL2-PML) was constructed by deleting residues 35
      64 of PML. DeltaL2-PML requires calcium ions for both lipase and esterase
      activities as does PML, suggesting that it exhibits activity only when lid1 is
      fully open and anchored by the catalytically essential calcium ion, as does PML.
      However, when the enzymatic activity was determined using triacetin, the activity
      of PML exponentially increased as the substrate concentration reached and
      increased beyond the critical micellar concentration, while that of DeltaL2-PML
      did not. These results indicate that PML undergoes interfacial activation, while
      DeltaL2-PML does not. The activities of DeltaL2-PML for long-chain triglycerides
      significantly decreased while its activity for fatty acid ethyl esters increased,
      compared with those of PML. Comparison of the tertiary models of DeltaL2-PML in a
      closed and open conformation, which are optimized by molecular dynamics
      simulation, with the crystal structures of PML suggests that the hydrophobic
      surface area provided by lid1 and lid2 in an open conformation is considerably
      decreased by the deletion of lid2. We propose that the hydrophobic surface area
      provided by these lids is necessary to hold the micellar substrates firmly to the
      active site and therefore lid2 is required for interfacial activation of PML.

PMID- 22863358
TI  - Is primary prevention of Clostridium difficile infection possible with specific
      probiotics?
AB  - BACKGROUND: The efficacy of probiotics for the prevention of Clostridium
      difficile infection (CDI) is highly controversial, particularly with regard to
      the prevention of recurrent CDI. We hypothesize that primary prevention of CDI
      among patients receiving antibiotics might be a more achievable goal for
      probiotics than prevention in patients with previous CDI where the host flora is
      markedly altered. METHODS: We conducted a literature search for randomized,
      placebo-controlled efficacy studies of probiotic use among adults receiving
      antibiotics, in which CDI was one of the outcomes measured. In addition, we
      conducted meta-analyses of probiotics that were included in more than one
      randomized trial. RESULTS: Eleven studies were identified; most were seriously
      underpowered to determine the efficacy of probiotics in the prevention of CDI.
      Two showed significantly lower rates of CDI among the probiotic recipients. A
      meta-analysis of three studies that used the probiotic combination Lactobacillus
      acidophilus CL1285 and Lactobacillus casei LBC80R and a combined analysis of
      those studies with four studies that used Saccharomyces boulardii, showed lower
      CDI rates in recipients of probiotics compared with recipients of placebo (risk
      ratio=0.39; 95% confidence interval 0.19-0.79). CONCLUSIONS: While potential
      flaws in study design were identified, a review of the available literature
      suggests that the primary prevention of CDI with specific probiotic agents may be
      achievable. Additional studies of sufficient size and with rigorous design are
      needed to confirm these findings.

PMID- 22863359
TI  - Fast accurate missing SNP genotype local imputation.
AB  - BACKGROUND: Single nucleotide polymorphism (SNP) genotyping assays normally give
      rise to certain percents of no-calls; the problem becomes severe when the target
      organisms, such as cattle, do not have a high resolution genomic sequence.
      Missing SNP genotypes, when related to target traits, would confound downstream
      data analyses such as genome-wide association studies (GWAS). Existing methods
      for recovering the missing values are successful to some extent - either accurate
      but not fast enough or fast but not accurate enough. RESULTS: To a target missing
      genotype, we take only the SNP loci within a genetic distance vicinity and only
      the samples within a similarity vicinity into our local imputation process. For
      missing genotype imputation, the comparative performance evaluations through
      extensive simulation studies using real human and cattle genotype datasets
      demonstrated that our nearest neighbor based local imputation method was one of
      the most efficient methods, and outperformed existing methods except the time
      consuming fastPHASE; for missing haplotype allele imputation, the comparative
      performance evaluations using real mouse haplotype datasets demonstrated that our
      method was not only one of the most efficient methods, but also one of the most
      accurate methods. CONCLUSIONS: Given that fastPHASE requires a long imputation
      time on medium to high density datasets, and that our nearest neighbor based
      local imputation method only performed slightly worse, yet better than all other
      methods, one might want to adopt our method as an alternative missing SNP
      genotype or missing haplotype allele imputation method.

PMID- 22863360
TI  - Improved neurologically intact survival with the use of an automated, load
      distributing band chest compression device for cardiac arrest presenting to the
      emergency department.
AB  - INTRODUCTION: It has been unclear if mechanical cardiopulmonary resuscitation
      (CPR) is a viable alternative to manual CPR. We aimed to compare resuscitation
      outcomes before and after switching from manual CPR to load-distributing band
      (LDB) CPR in a multi-center emergency department (ED) trial. METHODS: We
      conducted a phased, prospective cohort evaluation with intention-to-treat
      analysis of adults with non-traumatic cardiac arrest. At these two urban EDs,
      systems were changed from manual CPR to LDB-CPR. Primary outcome was survival to
      hospital discharge, with secondary outcome measures of return of spontaneous
      circulation, survival to hospital admission and neurological outcome at
      discharge. RESULTS: A total of 1,011 patients were included in the study, with
      459 in the manual CPR phase (January 01, 2004, to August 24, 2007) and 552
      patients in the LDB-CPR phase (August 16, 2007, to December 31, 2009). In the LDB
      phase, the LDB device was applied in 454 patients (82.3%). Patients in the manual
      CPR and LDB-CPR phases were comparable for mean age, gender and ethnicity. The
      mean duration from collapse to arrival at ED (min) for manual CPR and LDB-CPR
      phases was 34:03 (SD16:59) and 33:18 (SD14:57) respectively. The rate of survival
      to hospital discharge tended to be higher in the LDB-CPR phase (LDB 3.3% vs
      Manual 1.3%; adjusted OR, 1.42; 95% CI, 0.47, 4.29). There were more survivors in
      LDB group with cerebral performance category 1 (good) (Manual 1 vs LDB 12, P =
      0.01). Overall performance category 1 (good) was Manual 1 vs LDB 10, P = 0.06.
      CONCLUSIONS: A resuscitation strategy using LDB-CPR in an ED environment was
      associated with improved neurologically intact survival on discharge in adults
      with prolonged, non-traumatic cardiac arrest.

PMID- 22863361
TI  - [Therapeutic monoclonal antibodies in oncology].
AB  - Advances in bioengineering have lead to the possibility to conduct large scale
      production of monoclonal antibodies (MoAB) and to reduce progressively the murine
      component from 30% (chimeric MoAB) to 5% (humanized MoAB) to 0% (human MoAB).
      Three types of extracellular components are targeted in solid tumours: (1) Growth
      factors with transmembrane tyrosine kinase receptors either of tumour cells
      (IGF1) or endothelial cells (Bevacizumab). Bevacizumab has activity additive to
      that of chemotherapy in advanced colorectal, non squamous lung, ovarian,
      metastatic breast cancers and glioblastomas; (2) Extracellular domain of those
      transmembrane receptors: EGFR in colorectal cancer if no activating of KRAS with
      cetuximab and panitumumab, head and neck carcinomas with radiotherapy, and
      probably squamous lung cancers. Anti-ERBB2 MoAb are now a constitutive part of
      therapy of ERBB2 positive breast cancers at any stage; (3) Differentiation
      cluster regulating relationship ot tumour and stromal cells and in particular
      immunologic effectors. This is the case of anti-CTLA4 MoAB ipilimumab which
      activates and amplifies immunological cytotoxic response against melanoma with
      improved survival. These activities are achieved to the expense of class, target
      related toxicity conditioned by expression of the target on normal cells and or
      mechanism of action (immunological toxicity with ipilimumab). Of note a
      synergistic or additive activity with valid treatment regimens of targeted
      cancers and now targeted small molecules.

PMID- 22863363
TI  - Learning non-adjacent regularities at age 0 ; 7.
AB  - One important mechanism suggested to underlie the acquisition of grammar is rule
      learning. Indeed, infants aged 0 ; 7 are able to learn rules based on simple
      identity relations (adjacent repetitions, ABB: "wo fe fe" and non-adjacent
      repetitions, ABA: "wo fe wo", respectively; Marcus et al., 1999). One unexplored
      issue is whether young infants are able to process both adjacent and non-adjacent
      repetitions. As the previous studies always compared the two types of repetition
      structures directly, the ability to learn only one of them was sufficient for
      successful discrimination in these tasks. The present study reports two
      experiments, in which we test the ability of infants aged 0 ; 7 to discriminate
      adjacent and non-adjacent repetition structures against random controls (ABB vs.
      ABC and ABA vs. ABC). We show that, contrary to some previous proposals, infants
      aged 0 ; 7 successfully discriminate both repetition types from random controls,
      but show no spontaneous preference for either of them. 

PMID- 22863362
TI  - Effect of in-home and community-based services on the functional status of
      elderly in the long-term care insurance system in Japan.
AB  - BACKGROUND: Japan is setting the pace among aging societies of the world. In
      2005, Japan became the country with the highest proportion of elderly persons in
      the world. To deal with the accelerated ageing population and with an increased
      demand for long-term care services, in April 2000 the Japanese government
      introduced a mandatory social Long-Term Care Insurance System (LTCI), making long
      term care services a universal entitlement for elderly. Overseas literature
      suggests that the effectiveness of a home visiting program is uncertain in terms
      of preventing a decline in the functional status of elderly individuals. In
      Japan, many studies regarding factors associated with LTC service utilization
      have been conducted, however, limited evidence about the effect of LTC services
      on the progression of recipient disability is available. METHODS: Data were
      obtained from databases of the LTC insurer of City A. To examine the effect of in
      home and community-based services on disability status of recipients, a survival
      analysis in a cohort of moderately disabled elderly people, was conducted.
      RESULTS: The mean age of participants was 81 years old, and females represented
      69% of the participants. A decline or an improvement in functional status, was
      observed in 43% and 27% of the sample, respectively. After controlling for other
      variables, women had a significantly greater probability of improving their
      functional status during all phases of the observation period. The use of "one
      service" and the amount of services utilized (days/month), were marginally (p = <
      0.10) associated with a greater probability of improving their functional status
      at 12 months into the observation period. CONCLUSIONS: The observed effects of in
      home and community-based services on disability transition status were considered
      fairly modest and weak, in terms of their ability to improve or to prevent a
      decline in functional status. We suggest two mechanisms to explain these
      findings. First, disability transition as a measure of disability progression may
      not be specific enough to assess changes in functional status of LTCI recipients.
      Secondly, in-home and community-based services provided in City A, may be
      inappropriate in terms of intensity, duration or quality of care.

PMID- 22863364
TI  - Convenient synthesis of D- and L-xylo-1,2,3,4-alkane tetrols from a D-gluco
      configured common building block.
AB  - D-gluco-configured building block derived from D-(+)-gluconolactone has served as
      a common chiral template for the synthesis of enantiopure D- and L-xylo
      configured 1,2,3,4-alkane tetrols. This has enabled synthesis of medicinally
      important guggultetrols and their enantiomers from a common starting point.
      Wittig and Grignard reactions are the key steps used for the incorporation of
      lipophilic chain.

PMID- 22863365
TI  - Heat shock protein-inducing compounds as therapeutics to restore proteostasis in
      atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common clinical tachyarrhythmia associated
      with significant morbidity and mortality and is expected to affect approximately
      30 million North Americans and Europeans by 2050. AF is a persistent disease,
      caused by progressive, often age-related, derailment of proteostasis resulting in
      structural remodeling of the atrial cardiomyocytes. It has been widely
      acknowledged that the progressive nature of the disease hampers the effective
      functional conversion to sinus rhythm in patients and explains the limited effect
      of current drug therapies. Therefore, research is directed at preventing new
      onset AF by limiting the development of substrates underlying AF promotion.
      Upstream therapy refers to the use of drugs that modify the atrial substrate- or
      target-specific mechanisms of AF, with the ultimate aim to prevent the occurrence
      (primary prevention) and recurrence of the arrhythmia following (spontaneous)
      conversion and to prevent the progression of AF (secondary prevention). Recently,
      we observed that heat shock protein (HSP)-inducing drugs, such as
      geranylgeranylacetone, prevent derailment of proteostasis and remodeling of
      cardiomyocytes and thereby attenuate the AF substrate in cellular, Drosophila
      melanogaster, and animal experimental models. Also, correlative data from human
      studies were consistent with a protective role of HSPs in preventing the
      progression from paroxysmal AF to permanent AF and in the recurrence of AF. In
      this review, we discuss novel HSP-inducing compounds as emerging therapeutics for
      the primary and secondary prevention of AF.

PMID- 22863366
TI  - Modeling dilated cardiomyopathies in Drosophila.
AB  - During the past 100 years, the fruit fly, Drosophila melanogaster, has provided
      tremendous insights into genetics and human biology. Drosophila-based research
      utilizes powerful, genetically tractable approaches to identify new genes and
      pathways that potentially contribute to human diseases. New resources available
      in the fly research community have advanced the ability to examine genome-wide
      effects on cardiac function and facilitate the identification of structural,
      contractile, and signaling molecules that contribute to cardiomyopathies. This
      powerful model system continues to provide discoveries of novel genes and
      signaling pathways that are conserved among species and translatable to human
      pathophysiology.

PMID- 22863367
TI  - Microparticles as regulators of cardiovascular inflammation.
AB  - Microparticles are a heterogeneous group of membrane-coated vesicles that can act
      as signaling elements in the inflammatory processes. Once released from cells by
      membrane blebbing, microparticles become efficient vectors that exchange
      biological information between cells. Detectable in small amounts in peripheral
      blood of healthy individuals, elevated concentrations of microparticles
      originating from platelet, leukocyte, erythrocyte, and endothelial lineages are
      associated with a variety of pathophysiological conditions, including thrombosis,
      inflammation, sepsis, and metabolic disorders. This review summarizes the role of
      microparticles in modulating inflammation during cardiovascular diseases.

PMID- 22863368
TI  - Nutritional status influences peripheral immune cell phenotypes in healthy men in
      rural Pakistan.
AB  - Immune status is influenced by malnutrition, but how this factor interacts in
      developing countries and whether these differences are similar to those
      determined in industrialized countries, is unclear. To establish whether
      malnutrition-associated immune profiles in a developing country are similar to
      those in industrialized countries we analyzed peripheral blood immune cell
      phenotypes by polychromatic flow cytometry in 50 young and 50 elderly subjects.
      Data on anthropometrics and diet were collected through interviews. Plasma
      samples were analyzed for common clinical chemistry variables. Subjects in 4 BMI
      categories differed in their immune parameters demonstrating influence of
      nutritional status on immunity. This was greater within the young group and
      affected the CD4 subset more profoundly than the CD8 subset. No nutrition
      associated differences were seen in B or NK cells. CD8+ cells as a percentage of
      CD3+ T cells were positively associated with plasma CRP levels but not other
      factors. We conclude that there are differences in the immune signatures of
      obese, overweight and underweight versus normal-weight young and elderly, which
      seem broadly similar to the more extensively-documented state reported in
      industrialized countries, despite the marked societal, nutritional and many other
      differences.

PMID- 22863369
TI  - Family income trajectory during childhood is associated with adiposity in
      adolescence: a latent class growth analysis.
AB  - BACKGROUND: Childhood socioeconomic disadvantage has been linked with obesity in
      cross-sectional research, although less is known about how changes in
      socioeconomic status influence the development of obesity. Researchers have
      hypothesized that upward socioeconomic mobility may attenuate the health effects
      of earlier socioeconomic disadvantage; while downward socioeconomic mobility
      might have a negative influence on health despite relative socioeconomic
      advantages at earlier stages. The purpose of the current study was to
      characterize trajectories of family income during childhood, and to evaluate the
      influence of these trajectories on adiposity at age 15. METHODS: Data were
      collected as part of the Study of Early Child Care and Youth Development (SECCYD)
      between 1991 and 2007 at 10 sites across the United States. A latent class growth
      analysis (LCGA) was conducted to identify trajectories of family income from
      birth to 15 years of age. Analyses of covariance (ANCOVAs) were conducted to
      determine whether measures of adiposity differed by trajectory, while controlling
      for relevant covariates. RESULTS: The LCGA supported a 5-class trajectory model,
      which included two stable, one downward, and two upward trajectories. ANCOVAs
      indicated that BMI percentile, waist circumference, and skinfold thicknesses at
      age 15 differed significantly by trajectory, such that those who experienced
      downward mobility or stable low income had greater adiposity relative to the more
      advantaged trajectories. Conversely, upwardly mobile children and those with
      consistently adequate incomes had similar and more positive outcomes relative to
      the most disadvantaged trajectories. CONCLUSIONS: Findings suggest that promoting
      upward socioeconomic mobility among disadvantaged families may have a positive
      impact on obesity-related outcomes in adolescence.

PMID- 22863370
TI  - Genome-wide analysis of the grapevine stilbene synthase multigenic family:
      genomic organization and expression profiles upon biotic and abiotic stresses.
AB  - BACKGROUND: Plant stilbenes are a small group of phenylpropanoids, which have
      been detected in at least 72 unrelated plant species and accumulate in response
      to biotic and abiotic stresses such as infection, wounding, UV-C exposure and
      treatment with chemicals. Stilbenes are formed via the phenylalanine/polymalonate
      route, the last step of which is catalyzed by the enzyme stilbene synthase (STS),
      a type III polyketide synthase (PKS). Stilbene synthases are closely related to
      chalcone synthases (CHS), the key enzymes of the flavonoid pathway, as
      illustrated by the fact that both enzymes share the same substrates. To date,
      STSs have been cloned from peanut, pine, sorghum and grapevine, the only stilbene
      producing fruiting-plant for which the entire genome has been sequenced. Apart
      from sorghum, STS genes appear to exist as a family of closely related genes in
      these other plant species. RESULTS: In this study a complete characterization of
      the STS multigenic family in grapevine has been performed, commencing with the
      identification, annotation and phylogenetic analysis of all members and
      integration of this information with a comprehensive set of gene expression
      analyses including healthy tissues at differential developmental stages and in
      leaves exposed to both biotic (downy mildew infection) and abiotic (wounding and
      UV-C exposure) stresses. At least thirty-three full length sequences encoding
      VvSTS genes were identified, which, based on predicted amino acid sequences,
      cluster in 3 principal groups designated A, B and C. The majority of VvSTS genes
      cluster in groups B and C and are located on chr16 whereas the few gene family
      members in group A are found on chr10. Microarray and mRNA-seq expression
      analyses revealed different patterns of transcript accumulation between the
      different groups of VvSTS family members and between VvSTSs and VvCHSs. Indeed,
      under certain conditions the transcriptional response of VvSTS and VvCHS genes
      appears to be diametrically opposed suggesting that flow of carbon between these
      two competing metabolic pathways is tightly regulated at the transcriptional
      level. CONCLUSIONS: This study represents an overview of the expression pattern
      of each member of the STS gene family in grapevine under both constitutive and
      stress-induced conditions. The results strongly indicate the existence of a
      transcriptional subfunctionalization amongst VvSTSs and provide the foundation
      for further functional investigations about the role and evolution of this large
      gene family. Moreover, it represents the first study to clearly show the
      differential regulation of VvCHS and VvSTS genes, suggesting the involvement of
      transcription factors (TFs) in both the activation and repression of these genes.

PMID- 22863371
TI  - Evolving concepts on adjusting human resting energy expenditure measurements for
      body size.
AB  - Establishing if an adult's resting energy expenditure (REE) is high or low for
      their body size is a pervasive question in nutrition research. Early workers
      applied body mass and height as size measures and formulated the Surface Law and
      Kleiber's Law, although each has limitations when adjusting REE. Body composition
      methods introduced during the mid-20th century provided a new opportunity to
      identify metabolically homogeneous 'active' compartments. These compartments all
      show improved correlations with REE estimates over body mass-height approaches,
      but collectively share a common limitation: REE-body composition ratios are not
      'constant' but vary across men and women and with race, age and body size. The
      now-accepted alternative to ratio-based norms is to adjust for predictors by
      applying regression models to calculate 'residuals' that establish if an REE is
      relatively high or low. The distinguishing feature of statistical REE-body
      composition models is a 'non-zero' intercept of unknown origin. The recent
      introduction of imaging methods has allowed development of physiological tissue
      organ-based REE prediction models. Herein, we apply these imaging methods to
      provide a mechanistic explanation, supported by experimental data, for the non
      zero intercept phenomenon and, in that context, propose future research
      directions for establishing between-subject differences in relative energy
      metabolism.

PMID- 22863372
TI  - The morphology of single muscle fibre potentials - Part I: simulation study of
      the distortion introduced by the distant-interfering potentials.
AB  - Some morphologic aspects of human single fibre action potentials (SFAPs) are not
      sufficiently well-known. This uncertainty especially concerns the declining
      negative phase and the final positive phase (third phase) of SFAPs, as these
      parts are significantly affected by distant electrical activity. The incomplete
      characterisation of the SFAP shape is also explained by the limited knowledge of
      human intracellular action potentials (IAPs). The objectives of this study are to
      assess the morphologic features of human SFAPs and to derive information about
      the characteristics of human IAPs. To achieve this, the study has been divided
      into two parts. The present paper, Part I, aims to analyse the changes in the
      SFAP time-course introduced by distant-interfering potentials and to evaluate how
      these changes depend on the spike duration of the corresponding IAP. It was found
      that, for fibre-to-electrode distances shorter than about 0.2 mm, SFAPs generated
      by short-spike IAPs have a declining negative phase with a steep approximately
      constant slope that is largely unaffected by the potentials from distant fibres.
      For the same distances, SFAPs resulting from wide-spike IAPs have a declining
      negative phase with a slow return towards the baseline that is highly sensitive
      to distant-interfering potentials. The third phase of an SFAP is considerably
      distorted by distant potentials irrespective of the spike duration of the IAP.

PMID- 22863373
TI  - Benefits and risks of manual hyperinflation in intubated and mechanically
      ventilated intensive care unit patients: a systematic review.
AB  - INTRODUCTION: Manual hyperinflation (MH), a frequently applied maneuver in
      critically ill intubated and mechanically ventilated patients, is suggested to
      mimic a cough so that airway secretions are mobilized toward the larger airways,
      where they can easily be removed. As such, MH could prevent plugging of the
      airways. METHODS: We performed a search in the databases of Medline, Embase, and
      the Cochrane Library from January 1990 to April 2012. We systematically reviewed
      the literature on evidence for postulated benefits and risks of MH in critically
      ill intubated and mechanically ventilated patients. RESULTS: The search
      identified 50 articles, of which 19 were considered relevant. We included 13
      interventional studies and six observational studies. The number of studies
      evaluating physiological effects of MH is limited. Trials differed too much to
      permit meta-analysis. It is uncertain whether MH was applied similarly in the
      retrieved studies. Finally, most studies are underpowered to show clinical
      benefit of MH. Use of MH is associated with short-term improvements in lung
      compliance, oxygenation, and secretion clearance, without changes in outcomes. MH
      has been reported to be associated with short-term and probably clinically
      insignificant side effects, including decreases in cardiac output, alterations of
      heart rates, and increased central venous pressures. CONCLUSIONS: Studies have
      failed to show that MH benefits critically ill intubated and mechanically
      ventilated patients. MH is infrequently associated with short-term side effects.

PMID- 22863375
TI  - Combined use of a TST and the T-SPOT(r).TB assay for latent tuberculosis
      infection diagnosis before anti-TNF-alpha treatment.
AB  - BACKGROUND: Diagnosis of latent tuberculosis infection (LTBI) before anti-tumour
      necrosis factor (anti-TNF) treatment is important. However, the tuberculin skin
      test (TST) has limitations, and the role of interferon-gamma release assays has
      not yet been determined. OBJECTIVE: To evaluate the combined use of TST and the T
      SPOT((r)).TB (T-SPOT) assay prior to anti-TNF treatment. METHODS: From July 2004
      to March 2008, 281 patients were treated with anti-TNF agents. TST and T-SPOT
      were performed simultaneously at baseline. LTBI was defined as a positive TST of
      >=10 mm induration or as a positive T-SPOT if TST was >=5 mm but <10 mm. LTBI
      treatment was initiated, and patients were followed until August 2010. RESULTS:
      Positivity rates for TST and T-SPOT were respectively 33.6% (94/280) and 69.1%
      (186/269). LTBI treatment was initiated in 35.9% (101/281) of the patients, and
      active TB developed in 2.1% (6/281). Among the six TB patients, three were TST
      negative at baseline and received no LTBI treatment, whereas all four who
      underwent T-SPOT showed positive results at baseline. CONCLUSION: In a TB
      prevalent country, TST-defined LTBI diagnosis and treatment seem to be limited in
      preventing the development of TB before anti-TNF treatment. Further studies for T
      SPOT alone or the combined use of TST and T-SPOT (either test positive strategy)
      for detecting LTBI are necessary.

PMID- 22863374
TI  - Relationship between post-treatment platelet reactivity and ischemic and bleeding
      events at 1-year follow-up in patients receiving prasugrel.
AB  - BACKGROUND: Post-treatment platelet reactivity (PR) is associated with ischemic
      and bleeding events in patients receiving P2Y12 receptor antagonists. OBJECTIVES:
      We aimed to study the relationship between post-treatment PR after a 60-mg
      loading dose (LD) of prasugrel and 1-year thrombotic and bleeding events. METHOD:
      Patients were prospectively included in this multicenter study if they had a
      successful percutaneous coronary intervention (PCI) for acute coronary syndrome
      (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured
      using the Vasodilator-Stimulated Phosphoprotein index (VASP) after a prasugrel
      LD. Endpoints included the rate of thrombotic events and bleeding events at 1
      year. RESULTS: Among the 301 patients enrolled, 9 (3%) were lost to follow-up at
      1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and
      6.8%, respectively. Receiver-operating curve (ROC) analysis demonstrated an
      optimal cut-off value of 53.5% of PRI to predict thrombotic events at 1 year.
      Using this cut-off value we observed that patients exhibiting high on-treatment
      platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs.
      2.9%; P < 0.001). In parallel the optimal cut-off value of PRI to predict
      bleeding was 16%. Patients with a PRI <= 16% had a higher rate of bleeding events
      compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate
      analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95%
      confidence interval [CI]: 1.2-1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59-0.96; P
      = 0.024 [respectively, per 10% increase]). CONCLUSION: Platelet reactivity
      measurement after a prasugrel LD predicts both ischemic and bleeding events at 1
      year follow-up for ACS patients undergoing PCI.

PMID- 22863376
TI  - Profile of sight-threatening infectious keratitis: a prospective study.
AB  - PURPOSE: To prospectively study patients presenting with sight-threatening
      corneal ulcers with a view to identify the predisposing factors, causative
      organisms, clinical signs and treatment outcomes. METHODS: Prospectively, over 3
      year period, all cases with serious infective keratitis presenting to Queens
      Medical Hospital in Nottingham, UK, were recruited. Detailed information on the
      aetiology, culture results, signs & symptoms, the treatment given and the
      patient's response was collected and statistically analysed. RESULTS: One hundred
      and forty-three eyes of 129 patients were enrolled. Thirty-one patients were
      managed as out-patients, and 98 were treated as in-patients. The mean duration of
      admission was 9 +/- 13 days but was significantly higher in older patients and in
      Acanthamoeba keratitis cases. The important risk factors were ocular surface
      disease (32%), contact lens wear (26%) and previous ocular surgery (20%). Old
      age, deep infiltration, steroid use and poor initial vision were risk factors for
      prolonged course of treatment in bacterial keratitis. Corneal scrapings were done
      in 89% of the cases, but positive results were obtained only in 41.7%.
      Staphylococcus aureus was the most common isolated bacteria (18.8%). Acanthamoeba
      and Pseudomonas aeruginosa were the second and third common causative organisms
      (16.6% and 15%, respectively). Overall, 8.3% needed corneal grafting, which
      survived in 83.3% and eradicated infection in 100%. CONCLUSION: Microbial
      keratitis is an important cause of ocular morbidity. Previous ocular disease is
      an important predisposing factor. Old age, steroid use and poor presenting visual
      acuity are important prognostic indicators. Corneal grafting is an effective
      option for managing recalcitrant corneal infections.

PMID- 22863377
TI  - The effect of lightly crosslinked poly(carboxybetaine) hydrogel coating on the
      performance of sensors in whole blood.
AB  - Surface coatings of high packing densities have been routinely used to prevent
      nonspecific biomolecular and microorganism attachment. Hydrogels are another
      class of low fouling materials used to create three-dimensional matrixes for the
      free diffusion of small analytes or drugs and the high-loading of bio-recognition
      elements. However, biomolecules are subject to being entrapped within hydrogel
      matrixes or adhered onto hydrogel surfaces, making them questionable for use in
      whole blood. Here, we demonstrate the feasibility of a lightly crosslinked
      poly(carboxybetaine) hydrogel for use in whole blood, as opposite to the
      conventional wisdom of high packing density in surface coatings. Proteins are
      able to diffuse in and out of the matrix freely without being altered from their
      native conformations. In order to demonstrate its long-term performance in whole
      blood, this hydrogel was used as the surface coating of a glucose sensor. This
      work paves a new way for the development of surface coatings and sensors to
      achieve long-term stability and high performance in whole blood.

PMID- 22863378
TI  - Orthogonal nanometer-micrometer roughness gradients probe morphological
      influences on cell behavior.
AB  - Surface gradients facilitate rapid, high-throughput, systematic investigations in
      cell biology, materials science, and other fields. An important surface parameter
      is the surface roughness on both the micrometer and nanometer scales in the
      lateral direction. Two approaches have been combined to create two-dimensional
      roughness gradients by adding a nanoparticle density gradient onto a gradient of
      micro-featured roughness. All fabricated gradients were extensively characterized
      by SEM, AFM and optical profilometry to ensure their quality and to determine the
      roughness parameter Ra along the gradient. Additionally, a Fourier-transform
      approach was applied that allows a wavelength-dependent analysis of the surface
      topography. Since cell-culture assays require replicate experiments, a replica
      technique was used to create copies of the master gradient. Creating a negative
      replica in an elastomeric material served as a mold for a subsequent ceramic
      casting process. A positive replica was then formed from epoxy resin, which was
      subsequently coated with titanium and used for cell studies. Finally, these
      gradients were used in cell-culture assays to determine cellular response to
      surface roughness. The results clearly demonstrate the influence of surface
      roughness on the production by osteoblasts of markers for osteogenesis. It was
      shown that high roughness in the micrometer range, combined with an intermediate
      nanofeature density (30-40 features/MUm2), leads to the highest degree of
      osteopontin production after 14 days.

PMID- 22863379
TI  - The long-term stability and biocompatibility of fluorescent nanodiamond as an in
      vivo contrast agent.
AB  - Nanocarbon is a promising type of biomaterial for diagnostic and therapeutic
      applications. Fluorescent nanodiamond (FND) containing nitrogen-vacancy centers
      as built-in fluorophores is a new addition to the nanocarbon family. Here, we
      study the long-term stability and biocompatibility of 100-nm FNDs in rats through
      intraperitoneal injection over 5 months and develop the potential application of
      this biomaterial for sentinel lymph node mapping in a mouse model. From both in
      vivo and ex vivo fluorescence imaging as well as transmission electron
      microscopy, we found that the intradermally administered FND particles can be
      drained from the injection sites by macrophages and selectively accumulated in
      the axillary lymph nodes of the treated mice. Our measurements of water
      consumption, fodder consumption, body weight, and organ index showed no
      significant difference between control and FND-treated groups of the rats.
      Histopathological analysis of various tissues and organs indicated that FNDs are
      non-toxic even when a large quantity, up to 75 mg/kg body weight, of the
      particles was administered intraperitoneally to the living animals. With the
      properties of wide-ranging biocompatibility and perfect chemical and
      photophysical stability, FND is well suited for use as a contrast agent for long
      term in vivo imaging.

PMID- 22863380
TI  - Recombinant spider silk matrices for neural stem cell cultures.
AB  - Neural stem cells (NSCs) have the capacity to differentiate into neurons,
      astrocytes, and oligodendrocytes. Accordingly, NSCs hold great promise in drug
      screening and treatment of several common diseases. However, a major obstacle in
      applied stem cell research is the limitation of synthetic matrices for culturing
      stem cells. The objective of this study was to evaluate the suitability of
      recombinant spider silk (4RepCT) matrices for growth of NSCs. NSCs isolated from
      the cerebral cortices of mid-gestation rat embryos were cultured on either 4RepCT
      matrices or conventional poly-L-ornithine and fibronectin (P + F) coated
      polystyrene plates. From 48 h of culture, no significant differences in cell
      proliferation or viability were detected in NSC cultures on 4RepCT compared to
      control matrices (polystyrene plates coated with P + F). The NSCs retained an
      undifferentiated state, displaying low or no staining for markers of
      differentiated cells. Upon stimulation NSCs grown on 4RepCT differentiated
      efficiently into neuronal and astrocytic cells to virtually the same degree as
      control cultures, but a slightly less efficient oligodendrocyte differentiation
      was noted. We suggest that recombinant spider silk matrices provide a functional
      microenvironment and represent a useful tool for the development of new
      strategies in neural stem cell research.

PMID- 22863381
TI  - Size-dependent genotoxicity of graphene nanoplatelets in human stem cells.
AB  - Reduced graphene oxide nanoplatelets (rGONPs) were synthesized by sonication of
      covalently PEGylated GO sheets followed by a chemical reduction using hydrazine
      and bovine serum albumin. Human mesenchymal stem cells (hMSCs), as a fundamental
      factor in tissue engineering, were isolated from umbilical cord blood (as a
      recently proposed source for extracting fresh hMSCs) to investigate, for the
      first time, the size-dependent cyto- and geno-toxic effects of the rGONPs on the
      cells. The cell viability test showed significant cell destructions by 1.0 MUg/mL
      rGONPs with average lateral dimensions (ALDs) of 11+/-4 nm, while the rGO sheets
      with ALDs of 3.8+/-0.4 MUm could exhibit a significant cytotoxic effect only at
      highconcentration of 100 MUg/mL after 1 h exposure time. Although oxidative
      stress and cell wall membrane damage were determined as the main mechanism
      involved in the cytotoxicity of the rGO sheets, neither of them could completely
      describe the cell destructions induced by the rGONPs, especially at the
      concentrations<=1.0 MUg/mL. In fact, the rGONPs showed genotoxic effects on the
      stem cells through DNA fragmentations and chromosomal aberrations, even at low
      concentration of 0.1 MUg/mL. Our results present essential knowledge for more
      efficient and innocuous applications of graphene sheets and particularly
      nanoplatelets in upcoming nanotechnology-based tissue engineering as, e.g., drug
      transporter and scaffolds.

PMID- 22863382
TI  - Subclinical endocrine disorders. Preface.

PMID- 22863383
TI  - Pituitary incidentalomas.
AB  - The widespread use of sensitive neuroradiological imaging studies (i.e. computed
      tomography scan and magnetic resonance imaging) over the last years lead to the
      diagnosis of an increased number of asymptomatic pituitary lesions. The
      management of these so-called "pituitary incidentalomas" is still controversial,
      due to the limited data so far available on both the clinical relevance and the
      natural history of such incidentally discovered pituitary masses. Most pituitary
      incidentalomas are less than 1 cm in diameter (microincidentalomas) and are
      pituitary adenomas. Although these tumours are in general hormonally inactive,
      all the patients with incidentalomas should be screened for pituitary hypo- or
      hyper-function. Macroincidentalomas have greater growth potential and, when
      associated with hypopituitarism and/or visual disturbances, should be surgically
      removed. Conversely, incidentalomas not associated with hormonal alterations and
      dimensionally stable could be managed conservatively. This review will focus on
      the last data on the natural history and clinical management of pituitary
      incidentalomas.

PMID- 22863384
TI  - Adrenal incidentaloma.
AB  - Adrenal incidentaloma is a common clinical problem and its prevalence, in
      radiological studies, comes close to that of autoptic data as a result of imaging
      technological advances. The diagnostic challenge is to distinguish the majority
      of benign lesions from other masses, either malignant or hormone secreting, which
      require further therapy. The imaging evaluation (unenhanced CT and MRI) can
      differentiate malignant to benign lesions because the benign lesions have high
      lipid content. All patients should be tested for hypercortisolism and
      pheochromocytoma whereas aldosteronism should be tested in hypertensive patients
      only. The optimal diagnostic management for adrenal incidentaloma is still
      controversial, and the endocrinologist must devise a cost-effective approach
      taking into account the extensive endocrine work-up and imaging investigations
      that may be necessary. A tailored strategy may be based on the selection of
      patients at increased risk who require a careful and extensive follow-up among
      the vast majority of patients who require a simplified follow-up.

PMID- 22863385
TI  - Thyroid microcarcinoma.
AB  - Nowadays the most commonly occurring differentiated thyroid cancer in many
      countries is a microcarcinoma in patients older than 45 years, incidentally found
      during neck ultrasound. In view of their low morbidity and mortality, the crucial
      point is how to manage such microcarcinomas. Recently published European and
      American guidelines aim to minimize the diagnostic and therapeutic procedures
      without affecting the diagnostic accuracy and the therapeutic effectiveness,
      keeping in mind that we are dealing with patients who have a normal life
      expectancy and to whom we have to guarantee an excellent quality of life. The
      present review will summarize the clinical and pathological features of thyroid
      microcarcinoma, including its definition, prevalence, presentation, pathology,
      genetic, clinical impact and will try to derive from them a rationale for
      therapeutic and diagnostic intervention.

PMID- 22863386
TI  - Natural history, diagnosis and management of subclinical thyroid dysfunction.
AB  - Subclinical thyroid dysfunction (STD) represents a condition of slight thyroid
      hormone excess or deficiency, which may be associated with important adverse
      effects. This review will focus on the natural history, diagnosis and management
      of subclinical thyroid dysfunction. Since STD is only detected as a thyroid
      stimulating hormone (TSH) abnormality, it is essential to exclude transient
      causes of abnormal serum TSH before treating this disorder. Treatment of
      subclinical hyperthyroidism (SHyper) is recommended in elderly patients with
      undetectable serum TSH for the increased risk of atrial fibrillation,
      osteoporosis and bone fractures and for the higher risk of progression to overt
      disease. Treatment of subclinical hypothyroidism should be considered in patients
      with serum TSH above 10 mU/L for the increased risk of progression to overt
      hypothyroidism and the increased risk of coronary heart disease and heart failure
      events, which have been documented in patients with TSH increase above 10 mU/L.
      About 75% of patients with STD have mild dysfunction. The mild form of STD (low
      but detectable serum TSH in SHyper and mild increased serum TSH between 5 and 9
      mU/L in SHypo is associated with a minor risk of disease progression to overt
      dysfunction. The best treatment for STD remains controversial. Treatment of the
      mild form of STD should be considered after evaluating the patients' age, the
      adverse risk factors, the potential beneficial effects of treating this disorder
      and any underlying co-morbidities. Mild SHypo should be treated in infertile and
      pregnant women.

PMID- 22863388
TI  - Subclinical hypopituitarism.
AB  - The presence of subclinical or minor pituitary hormone deficiencies could be
      recognised in clinical practice and might represent intermediate situations among
      normal pituitary hormone secretion and clinical hypopituitarism. However, this
      entity has not been correctly identified and associated clinical impairment and
      even more, long-term consequences regarding to morbidity and mortality, strongly
      related to clinical hypopituitarism, has not been correctly settled. Furthermore,
      best test or methods for diagnosis and the cut off to define these intermediate
      situates are also unknown. With this purpose, long-term controlled studies are
      needed to define correctly this entity, the appropriate methods for diagnosis and
      the potential benefits of substitutive hormone therapy in detected cases. The
      present review will focus on the available evidence concerning the prevalence,
      clinical features and diagnosis of subclinical hypopituitarism.

PMID- 22863387
TI  - Subclinical hyperfunctioning pituitary adenomas: the silent tumors.
AB  - Pituitary adenomas are classified by function as defined by clinical symptoms and
      signs of hormone hypersecretion with subsequent confirmation on
      immunohistochemical staining. However, positive immunostaining for pituitary cell
      types has been shown for clinically nonfunctioning adenomas, and this entity is
      classified as silent functioning adenoma. Most common in these subtypes include
      silent gonadotroph adenomas, silent corticotroph adenomas and silent somatotroph
      adenomas. Less commonly, silent prolactinomas and thyrotrophinomas are
      encountered. Appropriate classification of these adenomas may affect follow-up
      care after surgical resection. Some silent adenomas such as silent corticotroph
      adenomas follow a more aggressive course, necessitating closer surveillance.
      Furthermore, knowledge of the immunostaining characteristics of silent adenomas
      may determine postoperative medical therapy. This article reviews the incidence,
      clinical behavior, and pathologic features of clinically silent pituitary
      adenomas.

PMID- 22863389
TI  - Subclinical diabetes insipidus.
AB  - Subclinical central diabetes insipidus (CDI) can be the outcome of a number of
      diseases that affect the hypothalamus-infundibulum-post hypophysis axis. One of
      the most common forms of subclinical CDI is linked to an autoimmune pathogenesis
      even if other causes may be also responsible. Among these, pregnancy, traumatic
      and surgical brain injury and some infiltrative, vascular, infectious and
      neoplastic diseases have been reported with increasing frequency. The natural
      history of autoimmune CDI seems to evolve through 4 functional stages according
      to the presence of antibodies to vasopressin-secreting cells (AVPcAb) and the
      relationship between their behavior overtime, the variations of posterior
      pituitary function and the characteristics of hypothalamic-hypophyseal region on
      magnetic resonance imaging. This staging is of crucial importance for the
      therapeutic strategy, taking into account that some stages could be still
      reversible. Several medical treatments have been suggested to interrupt the
      progression toward clinical CDI but the results are still discussed.

PMID- 22863390
TI  - Subclinical primary aldosteronism.
AB  - Screening for primary aldosteronism was historically recommended in patients with
      moderate to severe and/or resistant hypertension. Patients with mild hypertension
      and normotensive subjects were therefore excluded from the screening. However, a
      considerable number of normotensive individuals without hypokalaemia may have
      subclinical forms of primary aldosteronism. In this review, we describe evidence
      supporting the idea that primary aldosteronism is not only confined to patients
      with moderate to severe and/or resistant hypertension, but also exists in
      patients with mild hypertension and even in those with normotension. We discuss
      possible aetiologies, screening and diagnostic techniques and treatment options
      of the normotensive form of primary aldosteronism. The natural history, adverse
      effects and best treatment of this disease still remain to be resolved. The long
      term follow-up studies of normotensive primary aldosteronism patients who receive
      neither adrenal surgery nor treatment with mineralocorticoid receptor antagonists
      might help to solve these problems.

PMID- 22863391
TI  - Subclinical Cushing's syndrome.
AB  - The routine use of abdominal procedure has significantly increased the incidental
      finding of adrenal masses. The prevalence of these tumors, commonly defined as
      adrenal incidentalomas, ranges between 2-3% in autopsy and 4% in radiological
      series, reaching 5-8% in oncological studies and increasing with patients age.
      Although clinically silent, in 5-20% of cases, adrenal incidentalomas are
      responsible for a subtle cortisol overproduction, commonly defined as
      "subclinical Cushing's syndrome" (SCS). This term is used to describe autonomous
      cortisol secretion in patients who don't have the typical signs and symptoms of
      hypercortisolism. The optimal strategy for identification and management of SCS
      is unknown; the standard biochemical tests used to screen for overt Cushing's
      syndrome are generally ill-suited to the assessment of patients who have no, or
      only very mild signs of cortisol excess, then many tests aimed to study the
      hypothalamus-pituitary-adrenal axis (HPA) axis do not have sufficient sensitivity
      to recognize very mild degree of cortisol excess. An increased frequency of
      hypertension, central obesity, impaired glucose tolerance or diabetes,
      hyperlipemia and osteoporosis has been described in patients with SCS since
      patients are exposed to a chronic albeit slight, cortisol excess; however, there
      is not evidence-based demonstration of long term complications and, consequently,
      the management of this condition is largely empirical. Adrenalectomy or medical
      management of associated disease has been indicated as therapeutic options due to
      lack of data demonstrating the superiority of a surgical or non-surgical
      treatment.

PMID- 22863393
TI  - Hypoparathyroidism.
AB  - Hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia and low or
      inappropriately normal levels of parathyroid hormone (PTH).
      Pseudohypoparathyroidism is characterized by similar findings however PTH is
      elevated due to PTH resistance. PTH is a key calcium regulating hormone essential
      for calcium homeostasis, vitamin D-dependant calcium absorption, renal calcium
      reabsorption and renal phosphate clearance. The most common cause of
      hypoparathyroidism is iatrogenic in the setting of anterior neck surgery.
      Hypoparathyroidism may be due to congenital or acquired disorders. Causes include
      autoimmune diseases, genetic abnormalities, destruction or infiltrative disorders
      of the parathyroids. Impaired secretion of PTH may be seen with hypomagnesemia or
      hypermagnesemia Work-up includes a comprehensive history, physical examination,
      and a relevant biochemical investigation. Treatment of symptomatic or profound
      asymptomatic hypocalcemia (Corrected Calcium (Ca) < 1.9 mmol/L) is aimed at rapid
      intravenous administration of calcium and oral supplementation of vitamin D
      metabolites. Oral calcium and vitamin D analogs are critical in the treatment of
      hypocalcemia. In the long-term management of hypoparathyroidism thiazide
      diuretics are of value as they enhance renal calcium reabsorption and increase
      serum calcium and are of particular benefit in those with activating mutations of
      the calcium-sensing receptor. Parathyroid hormone replacement is of great value
      in improving serum calcium and lowering serum phosphate as well as the doses of
      calcium and calcitriol supplementation required. It has been shown to lower
      urinary calcium losses. Careful monitoring of vitamin D, phosphorous, and calcium
      is necessary during acute and long-term therapy. Although hypocalcemic patients
      commonly present with symptoms of neuromuscular irritability with perioral
      numbers paresthesias, tingling, seizures and, bronchospasm; hypocalcemia may be
      identified on the biochemical profile of an asymptomatic patient.

PMID- 22863392
TI  - Subclinical phaeochromocytoma.
AB  - Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy
      studies indicate that relatively large numbers of these tumours remain
      undiagnosed during life. This may reflect non-specific signs and symptoms and low
      medical alertness in evaluating the clinical picture or it may reflect a silent
      clinical presentation - the subclinical phaeochromocytoma. The associated
      clinical picture depends on the capacity of the tumours to release catecholamines
      and sometimes biologically active peptides. Hypertension is the hallmark of
      catecholamine release, but the amount, type and pattern of catecholamine
      secretion is extremely variable. Some tumours have low or intermittent secretory
      activity, some produce mainly or solely dopamine, while others very rarely do not
      synthesize or release any catecholamines (non-secretory or non-functional
      tumours). Such tumours may present with mild or even absent signs and symptoms of
      catecholamine excess. Low secretory activity may reflect small tumour size or
      differences in secretory phenotypes associated with the biochemical and genetic
      background of the tumours. Tumours due to succinate dehydrogenase subunit B
      mutations are often subclinical, poorly differentiated, contain low amounts of
      catecholamines, and are usually malignant at diagnosis. Adrenoceptor
      desensitization can result in a subclinical presentation, even when catecholamine
      levels are high. Subclinical phaeochromocytomas are often discovered as
      incidentalomas during radiological procedures or during routine screening for
      phaeochromocytoma in carriers of mutations in one of the ten currently identified
      tumour susceptibility genes. Undiagnosed phaeochromocytomas, whether or not
      subclinical and even if biologically benign, may cause extremely deleterious
      consequences or even death, following abrupt release of catecholamines.

PMID- 22863394
TI  - Subclinical vitamin D deficiency.
AB  - The optimal vitamin D status, as defined by serum 25-hydroxyvitamin D [25(OH)D],
      is still controversial. Some individuals are at risk for subclinical vitamin D
      deficiency, as defined by serum 25(OH)D levels between 25 and 75 nmol/L, and up
      to 80-100% of the entire population can display inadequate serum 25(OH)D values
      depending on latitude and seasonality. The clinical manifestation of extreme
      vitamin D deficiency, i.e. rickets and osteomalacia, are rare. Levels of 25(OH)D
      >= 50 nmol/L are required for optimal musculoskeletal health. However, levels of
      25(OH)D above 75 nmol/L may be necessary to maximize musculoskeletal benefits and
      take advantage of the extraskeletal actions of vitamin D. This review will
      summarize the actual positions on the boundaries of subclinical vitamin D
      deficiency, the main available evidence on the effects of inadequate vitamin D
      status on skeletal and extraskeletal targets and supplementation strategies.

PMID- 22863396
TI  - Thyroid dermopathy and acropachy.
AB  - Graves' disease is an autoimmune condition commonly associated with thyroid
      dysfunction and with anti-thyroid antibodies, usually TSH receptor stimulating
      antibodies. Thyroid autoimmunity also may be associated with extra thyroidal
      manifestations. Most common extra thyroidal manifestation is ophthalmopathy. Less
      common is thyroid dermopathy, usually occurring in pretibial area. Dermopathy is
      almost always associated with ophthalmopathy and in severe cases with acropachy.
      A common antigen with thyroid in tissues of the skin and the eyes, most likely
      TSH receptor, is involved in pathogenesis of extra thyroidal manifestations.
      Presence of dermopathy and acropachy are predictors of severity of autoimmune
      process. Local corticosteroid application is the standard therapy for dermopathy.
      Response to therapy is good in mild cases and poor in severe cases. Immune
      modulators and biotherapies are undergoing randomized trials for ophthalmopathy
      component of Graves' disease. Any therapy proven to be effective for
      ophthalmopathy can be utilized in future for management of dermopathy.

PMID- 22863395
TI  - Subclinical male hypogonadism.
AB  - Male hypogonadism is traditionally defined as the inadequate production of
      testosterone and impaired spermatozoa generation in the presence of elevated or
      reduced levels of gonadotropins. A more frequent measurement of testosterone
      levels and the development of highly sensitive and specific assays have led to
      the detection of less clinically evident gonadal dysfunction, in which small
      biochemical alterations may or may not be accompanied by signs and symptoms. This
      condition is called "compensated" or "subclinical" hypogonadism. To determine
      whether subclinical hypogonadism is a paraphysiological state, a clinical
      condition in itself, or a precursor to overt hypogonadism, we carried out a
      literature review with the aim of establishing a practical approach to
      subclinical hypogonadism.

PMID- 22863397
TI  - Promoting community knowledge and action for malaria control in rural Cambodia:
      potential contributions of Village Malaria Workers.
AB  - BACKGROUND: Cambodia has been investing in Village Malaria Workers (VMWs) to
      improve malaria case management in rural areas. This study assessed the quality
      of the VMWs' services compared to those by a government-run health center from
      the perspective of community members. We focused on VMWs' contribution to promote
      their action to control malaria. A community-based cross-sectional study was
      conducted in Kampot province in 2009. Interviews were conducted at every
      accessible household in a village with VMWs (n = 153) and a village with a health
      center (n = 159), using interviewer administered questionnaire. Preference of the
      interview was given to female household head. Multiple regression analyses were
      run to compare knowledge about malaria, preventive measures taken, and time
      before first malaria treatment between the two villages. FINDINGS: The villagers
      perceived the VMWs' services equally as good as those provided by the health
      center. After controlling for confounding factors, the following indicators did
      not show any statistical significance between two villages: community members'
      knowledge about malaria transmission (AOR = 0.60, 95% CI = 0.30-1.22) and
      government-recommended antimalarial (AOR = 0.55, 95% CI = 0.25-1.23), preventive
      measures taken (Beta = -0.191, p = 0.315), and time before the first treatment
      (Beta = 0.053, p = 0.721). However, knowledge about malaria symptoms was
      significantly lower in the village with VMWs than the village with a health
      center (AOR = 0.40, 95% CI = 0.19-0.83). CONCLUSIONS: VMWs played an equivalent
      role as the health center in promoting malaria knowledge, action, and effective
      case management. Although VMWs need to enhance community knowledge about malaria
      symptoms, the current government policy on VMWs is reasonable and should be
      expanded to other malaria endemic villages.

PMID- 22863398
TI  - NMR investigations of the dual targeting peptide of Thr-tRNA synthetase and its
      interaction with the mitochondrial Tom20 receptor in Arabidopsis thaliana.
AB  - Most mitochondrial proteins are synthesized in the cytosol as precursor proteins
      containing an N-terminal targeting peptide and are imported into mitochondria
      through the import machineries, the translocase of the outer mitochondrial
      membrane (TOM) and the translocase of the inner mitochondrial membrane (TIM). The
      N-terminal targeting peptide of precursor proteins destined for the mitochondrial
      matrix is recognized by the Tom20 receptor and plays an important role in the
      import process. Protein import is usually organelle specific, but several plant
      proteins are dually targeted into mitochondria and chloroplasts using an
      ambiguous dual targeting peptide. We present NMR studies of the dual targeting
      peptide of Thr-tRNA synthetase and its interaction with Tom20 in Arabidopsis
      thaliana. Our findings show that the targeting peptide is mostly unstructured in
      buffer, with a propensity to form alpha-helical structure in one region, S6-F27,
      and a very weak beta-strand propensity for Q34-Q38. The alpha-helical structured
      region has an amphiphilic character and a phichichiphiphi motif, both of which
      have previously been shown to be important for mitochondrial import. Using NMR we
      have mapped out two regions in the peptide that are important for Tom20
      recognition: one of them, F9-V28, overlaps with the amphiphilic region, and the
      other comprises residues L30-Q39. Our results show that the targeting peptide may
      interact with Tom20 in several ways. Furthermore, our results indicate a weak,
      dynamic interaction. The results provide for the first time molecular details on
      the interaction of the Tom20 receptor with a dual targeting peptide.

PMID- 22863399
TI  - Biofeedback improves postural control recovery from multi-axis discrete
      perturbations.
AB  - BACKGROUND: Multi-axis vibrotactile feedback has been shown to significantly
      reduce the root-mean-square (RMS) sway, elliptical fits to sway trajectory area,
      and the time spent outside of the no feedback zone in individuals with vestibular
      deficits during continuous multidirectional support surface perturbations. The
      purpose of this study was to examine the effect of multidirectional vibrotactile
      biofeedback on postural stability during discrete multidirectional support
      surface perturbations. METHODS: The vibrotactile biofeedback device mapped tilt
      estimates onto the torso using a 3-row by 16-column tactor array. The number of
      columns displayed was varied to determine the effect of spatial resolution upon
      subject response. Torso kinematics and center of pressure data were measured in
      six subjects with vestibular deficits. Transient and steady state postural
      responses with and without feedback were characterized in response to eight
      perturbation directions. Four feedback conditions in addition to the tactors off
      (no feedback) configuration were evaluated. Postural response data captured by
      both a force plate and an inertial measurement unit worn on the torso were
      partitioned into three distinct phases: ballistic, recovery, and steady state.
      RESULTS: The results suggest that feedback has minimal effects during the
      ballistic phase (body's outbound trajectory in response to the perturbation), and
      the greatest effects during the recovery (return toward baseline) and steady
      state (post-recovery) phases. Specifically, feedback significantly decreases the
      time required for the body tilt to return to baseline values and significantly
      increases the velocity of the body's return to baseline values. Furthermore,
      feedback significantly decreases root mean square roll and pitch sway and
      significantly increases the amount of time spent in the no feedback zone. All
      four feedback conditions produced comparable performance improvements. Incidences
      of delayed and uncontrolled responses were significantly reduced with feedback
      while erroneous (sham) feedback resulted in poorer performance when compared with
      the no feedback condition. CONCLUSIONS: The results show that among the displays
      evaluated in this study, no one tactor column configuration was optimal for
      standing tasks involving discrete surface perturbations. Feedback produced larger
      effects on body tilt versus center of pressure parameters. Furthermore, the
      subjects' performance worsened when erroneous feedback was provided, suggesting
      that vibrotactile stimulation applied to the torso is actively processed and
      acted upon rather than being responsible for simply triggering a stiffening
      response.

PMID- 22863400
TI  - STI service delivery in British Columbia, Canada; providers' views of their
      services to youth.
AB  - BACKGROUND: Little is known about service providers' knowledge, attitudes, and
      experiences in relation to the assessment, diagnosis, and treatment of
      individuals seeking care for sexually transmitted infections (STIs), and how they
      influence the delivery of services. The purpose of this study was to explore the
      perceptions of STI care providers and the ways they approached their practice.
      METHODS: We used a qualitative approach drawing on methods used in thematic
      analysis. Individual semi-structured in-depth interviews were conducted with 21
      service providers delivering STI services in youth clinics, STI clinics,
      reproductive health clinics, and community public health units in British
      Columbia (BC), Canada. RESULTS: Service providers' descriptions of their
      activities and roles were shaped by a number of themes including specialization,
      scarcity, and maintaining the status quo. The analysis suggests that service
      providers perceive, at times, the delivery of STI care to be inefficient and
      inadequate. CONCLUSION: Findings from this study identify deficits in the
      delivery of STI services in BC. To understand these deficits, more research is
      needed to examine the larger health care structure within which service providers
      work, and how this structure not only informs and influences the delivery of
      services, but also how particular structural barriers impinge on and/or restrict
      practice.

PMID- 22863401
TI  - The decreased self-renewal potential of NPCs during human embryonic brain
      development with reduced activity of MAPKs.
AB  - Study of neural progenitor cells (NPCs) is important for treatment of degerative
      diseases in central nervous system. One of the key questions in NPCs
      transplantation therapy is about the understanding of which stage of the NPCs in
      brain development is ideal. Herein we investigated survival, proliferation and
      apoptosis of NPCs from 12 w, 16 w and 20 w human embryonic brain, meanwhile, the
      phosphorylation of mitogen-activated protein kinases (MAPKs) signaling were
      analyzed. The results showed that the survival, proliferation and cell division
      of 16 w and 20 w human NPCs significantly decreased comparing with 12 w human
      NPCs in vitro; and the NPCs apoptosis remarkably increased. Phosphorylation of
      ERK1/2 of 16 w and 20 w NPCs significantly decreased comparing with 12 w human
      NPCs, however phosphorylation of p38 MAPK increased. NPCs proliferation increase
      when ERK1/2 signaling is activated by PMA. The results demonstrated that self
      renewal potential of NPCs decreased in culture during human embryonic brain
      development, the activity of ERK signaling pathway were decreased, and suggest
      NPCs from 12-week fetuses might be better donor for cell transplantation during
      the period of 12-20 weeks because of their advantage on survival and
      proliferation.

PMID- 22863402
TI  - Comparison of freezing tolerance, compatible solutes and polyamines in
      geographically diverse collections of Thellungiella sp. and Arabidopsis thaliana
      accessions.
AB  - BACKGROUND: Thellungiella has been proposed as an extremophile alternative to
      Arabidopsis to investigate environmental stress tolerance. However, Arabidopsis
      accessions show large natural variation in their freezing tolerance and here the
      tolerance ranges of collections of accessions in the two species were compared.
      RESULTS: Leaf freezing tolerance of 16 Thellungiella accessions was assessed with
      an electrolyte leakage assay before and after 14 days of cold acclimation at 4
      degrees C. Soluble sugars (glucose, fructose, sucrose, raffinose) and free
      polyamines (putrescine, spermidine, spermine) were quantified by HPLC, proline
      photometrically. The ranges in nonacclimated freezing tolerance completely
      overlapped between Arabidopsis and Thellungiella. After cold acclimation, some
      Thellungiella accessions were more freezing tolerant than any Arabidopsis
      accessions. Acclimated freezing tolerance was correlated with sucrose levels in
      both species, but raffinose accumulation was lower in Thellungiella and only
      correlated with freezing tolerance in Arabidopsis. The reverse was true for leaf
      proline contents. Polyamine levels were generally similar between the species.
      Only spermine content was higher in nonacclimated Thellungiella plants, but
      decreased during acclimation and was negatively correlated with freezing
      tolerance. CONCLUSION: Thellungiella is not an extremophile with regard to
      freezing tolerance, but some accessions significantly expand the range present in
      Arabidopsis. The metabolite data indicate different metabolic adaptation
      strategies between the species.

PMID- 22863403
TI  - Sentinel surveillance for influenza and other respiratory viruses in Cote
      d'Ivoire, 2003-2010.
AB  - BACKGROUND: Many countries in Africa have lacked sentinel surveillance systems
      for influenza and are under-represented in data used for global vaccine strain
      selection. OBJECTIVES: We describe 8 years of sentinel surveillance data and the
      contribution of influenza and other viruses to medically attended influenza-like
      illness (ILI) in Cote d'Ivoire. METHODS: Sentinel surveillance was established in
      2003. Nasopharyngeal (NP) specimens and epidemiologic data are collected from
      persons of all ages presenting with ILI at sentinel sites. Respiratory specimens
      have been tested for influenza using various viral and molecular diagnostic
      methods. A subset of 470 specimens collected from children aged 0-5 years were
      tested for multiple respiratory viruses using RT-PCR. RESULTS: From 2003 to 2010,
      5074 NP specimens were collected from patients with ILI. Overall, 969/5074 (19%)
      of these specimens tested positive for influenza. Seasonal influenza A(H1N1)
      viruses predominated during 5 years and influenza A(H3N2) viruses predominated
      during 3 years. Influenza B viruses cocirculated with influenza A viruses during
      each year from 2004 to 2010. Seasonal peaks in influenza circulation were
      observed during the months of May, June, and October, with the largest peak
      corresponding with the primary rainfall season. Of 470 specimens collected from
      children under aged 5 who were tested for multiple respiratory viruses, a viral
      respiratory pathogen was detected in 401/470 (85%) of specimens. Commonly
      detected viruses were RSV (113 of 470 specimens, 24%), rhinoviruses (85/470,
      18%), influenza (77/470, 16%), and parainfluenza (75/470, 16%). CONCLUSION: In
      Cote d'Ivoire, there is a significant annual contribution of influenza and other
      respiratory viruses to medically attended ILI.

PMID- 22863404
TI  - Combined bilateral lung-liver transplantation complicated by intraoperative right
      ventricular dysfunction and postoperative hepatic artery thrombosis.

PMID- 22863405
TI  - Intraoperative pulmonary vein examination by transesophageal echocardiography: an
      anatomic update and review of utility.

PMID- 22863406
TI  - Rotational thromboelastometry (ROTEM)-based coagulation management in cardiac
      surgery and major trauma.

PMID- 22863407
TI  - Effects of psyllium on metabolic syndrome risk factors.
AB  - High-fibre intake has been shown to reduce the risk of metabolic syndrome (MS),
      cardiovascular disease and type 2 diabetes. Psyllium is one of the most widely
      used fibre supplements because it is reasonably cheap and is better tolerated
      than other fibre supplements. The review of the literature supports the notion
      that the consumption of psyllium provides benefits to many components of the MS.
      Psyllium supplementation does improve glucose levels and insulin response, blood
      pressure, as well as lipid profile in both animals and humans, thereby reducing
      metabolic risk factors. Appetite has also been reported to decrease after the
      consumption of psyllium in most studies. Collectively, psyllium supplementation
      could be promoted to patients who present MS risk factors, such as
      hypercholesterolaemia, hypertriglyceridaemia and hyperglycaemia. It may also play
      a role in controlling body weight, body composition, appetite and hypertension,
      but further investigation is still required.

PMID- 22863408
TI  - Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein
      RNA interactions.
AB  - UV cross-linking and immunoprecipitation (CLIP) and individual-nucleotide
      resolution CLIP (iCLIP) are methods to study protein-RNA interactions in
      untreated cells and tissues. Here, we analyzed six published and two novel data
      sets to confirm that both methods identify protein-RNA cross-link sites, and to
      identify a slight uridine preference of UV-C-induced cross-linking. Comparing
      Nova CLIP and iCLIP data revealed that cDNA deletions have a preference for TTT
      motifs, whereas iCLIP cDNA truncations are more likely to identify clusters of
      YCAY motifs as the primary Nova binding sites. In conclusion, we demonstrate how
      each method impacts the analysis of protein-RNA binding specificity. 

PMID- 22863409
TI  - The impact of substituting SFA in dairy products with MUFA or PUFA on CVD risk:
      evidence from human intervention studies.
AB  - With the substantial economic and social burden of CVD, the need to modify diet
      and lifestyle factors to reduce risk has become increasingly important. Milk and
      dairy products, being one of the main contributors to SFA intake in the UK, are a
      potential target for dietary SFA reduction. Supplementation of the dairy cow's
      diet with a source of MUFA or PUFA may have beneficial effects on consumers' CVD
      risk by partially replacing milk SFA, thus reducing entry of SFA into the food
      chain. A total of nine chronic human intervention studies have used dairy
      products, modified through bovine feeding, to establish their effect on CVD risk
      markers. Of these studies, the majority utilised modified butter as their primary
      test product and used changes in blood cholesterol concentrations as their main
      risk marker. Of the eight studies that measured blood cholesterol, four reported
      a significant reduction in total and LDL-cholesterol (LDL-C) following chronic
      consumption of modified milk and dairy products. Data from one study suggested
      that a significant reduction in LDL-C could be achieved in both the healthy and
      hypercholesterolaemic population. Thus, evidence from these studies suggests that
      consumption of milk and dairy products with modified fatty acid composition,
      compared with milk and dairy products of typical milk fat composition, may be
      beneficial to CVD risk in healthy and hypercholesterolaemic individuals. However,
      current evidence is insufficient and further work is needed to investigate the
      complex role of milk and cheese in CVD risk and explore the use of novel markers
      of CVD risk.

PMID- 22863410
TI  - GRADE guidelines: 10. Considering resource use and rating the quality of economic
      evidence.
AB  - OBJECTIVES: In this article, we describe how to include considerations about
      resource utilization when making recommendations according to the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) approach. STUDY
      DESIGN AND SETTINGS: We focus on challenges with rating the confidence in effect
      estimates (quality of evidence) and incorporating resource use into evidence
      profiles and Summary of Findings (SoF) tables. RESULTS: GRADE recommends that
      important differences in resource use between alternative management strategies
      should be included along with other important outcomes in the evidence profile
      and SoF table. Key steps in considering resources in making recommendations with
      GRADE are the identification of items of resource use that may differ between
      alternative management strategies and that are potentially important to decision
      makers, finding evidence for the differences in resource use, making judgments
      regarding confidence in effect estimates using the same criteria used for health
      outcomes, and valuing the resource use in terms of costs for the specific setting
      for which recommendations are being made. CONCLUSIONS: With our framework,
      decision makers will have access to concise summaries of recommendations,
      including ratings of the quality of economic evidence, and better understand the
      implications for clinical decision making.

PMID- 22863411
TI  - On the representational systems underlying prospection: evidence from the event
      cueing paradigm.
AB  - The ability to think about the future-prospection-is central to many aspects of
      human cognition and behavior, from planning and decision making, to self-control
      and the construction of a sense of identity. Yet, the exact nature of the
      representational systems underlying prospection is not fully understood. Recent
      findings point to the critical role of episodic memory in imagining specific
      future events, but it is unlikely that prospection depends solely on this system.
      Using an event-cueing paradigm in two studies, we here show that specific events
      that people imagine might happen in their personal future are commonly embedded
      in broader event sequences-termed event clusters-that link a set of envisioned
      events according to causal and thematic relations. These findings provide novel
      evidence that prospection relies on multiple representational systems, with
      general autobiographical knowledge structures providing a frame that organizes
      imagined events in overarching event sequences. The results further suggest that
      knowledge about personal goals plays an important role in structuring these event
      sequences, especially for the distant future.

PMID- 22863412
TI  - Changing auditory time with prismatic goggles.
AB  - The aim of the present study was to explore the spatial organization of auditory
      time and the effects of the manipulation of spatial attention on such a
      representation. In two experiments, we asked 28 adults to classify the duration
      of auditory stimuli as "short" or "long". Stimuli were tones of high or low
      pitch, delivered left or right of the participant. The time bisection task was
      performed either on right or left stimuli regardless of their pitch (Spatial
      experiment), or on high or low tones regardless of their location (Tonal
      experiment). Duration of left stimuli was underestimated relative to that of
      right stimuli, in the Spatial but not in the Tonal experiment, suggesting that a
      spatial representation of auditory time emerges selectively when spatial-encoding
      is enforced. Further, when we introduced spatial-attention shifts using the
      prismatic adaptation procedure, we found modulations of auditory time processing
      as a function of prismatic deviation, which correlated with the interparticipant
      adaptation effect. These novel findings reveal a spatial representation of
      auditory time, modulated by spatial attention.

PMID- 22863413
TI  - Mapping sensorimotor sequences to word sequences: a connectionist model of
      language acquisition and sentence generation.
AB  - In this article we present a neural network model of sentence generation. The
      network has both technical and conceptual innovations. Its main technical novelty
      is in its semantic representations: the messages which form the input to the
      network are structured as sequences, so that message elements are delivered to
      the network one at a time. Rather than learning to linearise a static semantic
      representation as a sequence of words, our network rehearses a sequence of
      semantic signals, and learns to generate words from selected signals.
      Conceptually, the network's use of rehearsed sequences of semantic signals is
      motivated by work in embodied cognition, which posits that the structure of
      semantic representations has its origin in the serial structure of sensorimotor
      processing. The rich sequential structure of the network's semantic inputs also
      allows it to incorporate certain Chomskyan ideas about innate syntactic knowledge
      and parameter-setting, as well as a more empiricist account of the acquisition of
      idiomatic syntactic constructions.

PMID- 22863414
TI  - The flexibility of emotional attention: accessible social identities guide rapid
      attentional orienting.
AB  - There is extensive evidence that emotional-especially threatening-stimuli rapidly
      capture attention. These findings are often explained in terms of a hard-wired
      and relatively inflexible fear module. We propose an alternative, more flexible
      mechanism, arguing that motivational relevance is the crucial factor driving
      rapid attentional orienting. To test our hypothesis, we endowed initially neutral
      face stimuli with relevance by randomly assigning them to a social in-group or
      out-group during a 1-min learning phase, and used these faces as cues in a dot
      probe task to measure rapid attentional orienting. Across three experiments, we
      observed attentional orienting toward faces assigned to the out-group. Initial
      rapid orienting (after 100 ms, Experiments 1 and 2) was observed only for
      familiar faces for which group membership was explicitly encoded, suggesting that
      rapid orienting may be based on affectively charged memory traces. At a later
      time point (after 500 ms, Experiment 3), attention was deployed toward unfamiliar
      faces sharing a physical attribute (background color) with the familiar out-group
      faces, suggesting a more time-consuming on-line appraisal of the stimulus. The
      amount of attentional bias to out-group faces was correlated with individual
      differences in the accessibility of group identification. Our findings
      demonstrate that attentional prioritization mechanisms can be flexibly tuned by a
      brief learning phase of social identity. This is consistent with the idea that
      attention mechanisms subserving the selection and prioritization of emotional
      aspects of the environment are not static and hard-wired, but may rapidly adapt
      to recent changes in motivational contingencies.

PMID- 22863415
TI  - Contemporary management of primary immune thrombocytopenia in adults.
AB  - Immune thrombocytopenia (ITP) comprises a syndrome of diverse disorders that have
      in common immune-mediated thrombocytopenia, but that differ with respect to
      pathogenesis, natural history and response to therapy. ITP may occur in the
      absence of an evident predisposing etiology (primary ITP) or as a sequela of a
      growing list of associated conditions (secondary ITP). Primary ITP remains a
      diagnosis of exclusion and must be differentiated from non-autoimmune etiologies
      of thrombocytopenia and secondary causes of ITP. The traditional objective of
      management is to provide a hemostatic platelet count (> 20-30 * 10(9) L(-1) in
      most cases) while minimizing treatment-related toxicity, although treatment goals
      should be tailored to the individual patient and clinical setting.
      Corticosteroids, supplemented with either intravenous immune globulin G or anti
      Rh(D) as needed, are used as upfront therapy to stop bleeding and raise the
      platelet count acutely in patients with newly diagnosed or newly relapsed
      disease. Although most adults with primary ITP respond to first-line therapy, the
      majority relapse after treatment is tapered and require a second-line approach to
      maintain a hemostatic platelet count. Standard second-line options include
      splenectomy, rituximab and the thrombopoietin receptor agonists, romiplostim and
      eltrombopag. Studies that directly compare the efficacy, safety and cost
      effectiveness of these approaches are lacking. In the absence of such data, we do
      not favor a single second-line approach for all patients. Rather, we consider the
      pros and cons of each option with our patients and engage them in the decision
      making process.

PMID- 22863416
TI  - Cortical rhythm of No-go processing in humans: an MEG study.
AB  - OBJECTIVE: We investigated the characteristics of cortical rhythmic activity in
      No-go processing during somatosensory Go/No-go paradigms, by using
      magnetoencephalography (MEG). METHODS: Twelve normal subjects performed a warning
      stimulus (S1) - imperative stimulus (S2) task with Go/No-go paradigms. The
      recordings were conducted in three conditions. In Condition 1, the Go stimulus
      was delivered to the second digit, and the No-go stimulus to the fifth digit. The
      participants responded by pushing a button with their right thumb for the Go
      stimulus. In Condition 2, the Go and No-go stimuli were reversed. Condition 3 was
      the resting control. RESULTS: A rebound in amplitude was recorded in the No-go
      trials for theta, alpha, and beta activity, peaking at 600-900 ms. A suppression
      of amplitude was recorded in Go and No-go trials for alpha activity, peaking at
      300-600 ms, and in Go and No-go trials for beta activity, peaking at 200-300 ms.
      CONCLUSION: The cortical rhythmic activity clearly has several dissociated
      components relating to different motor functions, including response inhibition,
      execution, and decision-making. SIGNIFICANCE: The present study revealed the
      characteristics of cortical rhythmic activity in No-go processing.

PMID- 22863417
TI  - Inter-hemispherical functional coupling of EEG rhythms during the perception of
      facial emotional expressions.
AB  - OBJECTIVE: Brain rhythms of both hemispheres are involved in the processing of
      emotional stimuli but their interdependence between the two hemispheres is poorly
      known. Here we tested the hypothesis that passive visual perception of facial
      emotional expressions is related to a coordination of the two hemispheres as
      revealed by the inter-hemispherical functional coupling of brain
      electroencephalographic (EEG) rhythms. METHODS: To this aim, EEG data were
      recorded in 14 subjects observing emotional faces with neutral, happy or sad
      facial expressions (about 33% for each class). The EEG data were analyzed by
      directed transfer function (DTF), which estimates directional functional coupling
      of EEG rhythms. The EEG rhythms of interest were theta (about 4-6 Hz), alpha 1
      (about 6-8 Hz), alpha 2 (about 8-10 Hz), alpha 3 (about 10-12 Hz), beta 1 (13-20
      Hz), beta 2 (21-30 Hz), and gamma (31-44 Hz). RESULTS: In the frontal regions,
      inter-hemispherical DTF values were bidirectionally higher in amplitude across
      all frequency bands, during the perception of faces with sad compared to neutral
      or happy expressions. CONCLUSIONS: These results suggest that the processing of
      emotional negative facial expressions is related to an enhancement of a
      reciprocal inter-hemispherical flux of information in frontal cortex, possibly
      optimizing executive functions and motor control. SIGNIFICANCE: Dichotomical view
      of hemispherical functional specializations does not take into account remarkable
      reciprocal interactions between frontal areas of the two hemispheres during the
      processing of negative facial expressions.

PMID- 22863418
TI  - Sidestep cutting maneuvers in female basketball players: stop phase poses greater
      risk for anterior cruciate ligament injury.
AB  - BACKGROUND: Many non-contact anterior cruciate ligament (ACL) injuries in female
      basketball players occur during sidestep cutting. The objective of this study was
      to identify the phases of a sidestep cutting maneuver that place athletes at a
      greater risk for ACL injuries. METHODS: Ten healthy female collegiate basketball
      athletes were asked to perform sidestep cutting movements; the knee flexion and
      valgus angles as well as the electromyographic activity of the vastus lateral,
      vastus medial, biceps femoris, and semimembranosus muscles of the non-dominant
      leg were analyzed during the maneuver. RESULTS: The mean knee valgus angle peak
      tended to be greater during the stop phase than during the side-movement phase.
      The quadriceps activation during the stop phase was significantly higher than
      that during the side-movement phase. Moreover, the ratio of hamstring to
      quadriceps muscle activation during the stop phase was significantly lower than
      that during the side-movement phase, as assessed by surface electromyography.
      CONCLUSION: Female basketball athletes have a higher risk for ACL injury during
      the stop phase than during the side-movement phase of the sidestep cutting
      maneuver. LEVEL OF EVIDENCE: Level III.

PMID- 22863419
TI  - Fifty years in the thioredoxin field and a bountiful harvest.
AB  - Discovered 50 years ago as a hydrogen donor for the reduction of ribonucleotides,
      thioredoxin is currently recognized as a protein central to the regulation of
      multiple processes in the cell. Two meetings separated by a period of 30 years
      serve as benchmarks for assessing this transition-the first held in Berkeley
      (California) in 1981 and the other convened in 2011 in Sant Feliu de Guixols
      (Spain). The four of us contributing this article attended both meetings and thus
      have witnessed the development of the thioredoxin field and its notable extension
      in unanticipated new directions. In this Perspective we briefly recount the
      unfolding of this remarkable story.

PMID- 22863421
TI  - In response to the article: effect of peak flow monitoring on child asthma
      quality of life by Burkhart, P.V., Rayens, M.K., & Oakley, M.G.

PMID- 22863420
TI  - Transient inability to manage proteobacteria promotes chronic gut inflammation in
      TLR5-deficient mice.
AB  - Colitis results from breakdown of homeostasis between intestinal microbiota and
      the mucosal immune system, with both environmental and genetic influencing
      factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated
      intestinal proinflammatory gene expression and colitis with incomplete
      penetrance, providing a genetically sensitized system to study the contribution
      of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited
      transiently unstable microbiotas, with lasting differences in colitic T5KO, while
      their noncolitic siblings stabilized their microbiotas to resemble wild-type
      mice. Transient high levels of proteobacteria, especially enterobacteria species
      including E. coli, observed in close proximity to the gut epithelium were a
      striking feature of colitic microbiota. A Crohn's disease-associated E. coli
      strain induced chronic colitis in T5KO, which persisted well after the
      exogenously introduced bacterial species had been eliminated. Thus, an innate
      immune deficiency can result in unstable gut microbiota associated with low-grade
      inflammation, and harboring proteobacteria can drive and/or instigate chronic
      colitis.

PMID- 22863422
TI  - Internal and geriatric medicine: an alliance for the challenges of the elderly.

PMID- 22863423
TI  - Preoperative geriatric assessment: comprehensive, multidisciplinary and
      proactive.
AB  - With the changing global demographic pattern, our health care systems
      increasingly have to deal with a greater number of elderly patients, which
      consequently also takes its toll on our surgical services. The elderly are not
      simply older adults. They represent a heterogeneous branch of the population with
      specific physiological, psychological, functional and social issues that require
      individualised attention prior to surgery. Increased acknowledgement that
      chronological age alone is not an exclusion criterion, along with advances in
      surgical and anaesthetic techniques have today lead to decreased reluctance to
      deny the elderly surgical treatment. In order to ensure a safe perioperative
      period, we believe that a comprehensive, multidisciplinary and proactive
      preoperative assessment will be helpful to detect the multiple risk factors and
      comorbidities common in older patients, to assess functional status and
      simultaneously allow room for early preoperative interventions and planning of
      the intra- and postoperative period. In this review we outline the currently
      available preoperative geriatric risk assessment tools and provide an insight on
      how a comprehensive, multidisciplinary and proactive approach can help improve
      perioperative outcome.

PMID- 22863424
TI  - High value, cost-conscious care: an international imperative.
AB  - Health care costs in the United States are the highest in the world, and are
      continuing to rise at a level that is unsustainable. However, although this
      problem is more acute in the United States than elsewhere in the world, it is a
      challenge for all nations to control the costs of health care. The high cost of
      health care in the U.S. is not accompanied by a higher quality of care, but
      rather is related in large measure to health system "waste" that does not benefit
      patients but adds to cost. Representing approximately 30% of dollars spent on
      health care, this waste includes a significant amount of money spent on overuse
      and misuse of diagnostic testing, including screening tests. The American College
      of Physicians, the largest specialty society for physicians in the U.S.,
      representing internal medicine and all of its subspecialties, has embarked upon a
      High Value, Cost-Conscious Care initiative, aimed at identifying areas of overuse
      and misuse of care, and leading to development of guidelines, educational
      materials, and other resources targeted to health care providers, trainees, and
      the general public. It is incumbent upon physicians, non-physician health care
      professionals, patients, and other health care stakeholders to address the issue
      of reducing care that is not appropriate, both to improve the overall quality of
      care and to reduce the associated unsustainable financial burden to society.

PMID- 22863425
TI  - Diabetic gastrointestinal autonomic neuropathy: current status and new
      achievements for everyday clinical practice.
AB  - Gastrointestinal symptoms occur frequently among patients with diabetes mellitus
      and are associated with considerable morbidity. Diabetic gastrointestinal
      autonomic neuropathy represents a complex disorder with multifactorial
      pathogenesis, which is still not well understood. It appears to involve a
      spectrum of metabolic and cellular changes that affect gastrointestinal motor and
      sensory control. It may affect any organ in the digestive system. Clinical
      manifestations are often underestimated, and therefore autonomic neuropathy
      should be suspected in all diabetic patients with unexplained gastrointestinal
      symptoms. Advances in technology have now enabled assessment of gastrointestinal
      motor function. Moreover, novel pharmacological approaches, along with endoscopic
      and surgical treatment options, contribute to improved outcomes. This review
      summarises the progress achieved in diabetic gastrointestinal autonomic
      neuropathy during the last years, focusing on clinical issues of practical
      importance to the everyday clinician.

PMID- 22863426
TI  - Selection of tools for reconciliation, compliance and appropriateness of
      treatment in patients with multiple chronic conditions.
AB  - BACKGROUND: The healthcare models developed for patients with multiple chronic
      diseases agree on the need for improving drug therapy in these patients. The
      issues of patient compliance, appropriateness of prescriptions and the
      reconciliation process are of vital importance for patients receiving multiple
      drug treatment. OBJECTIVE: To identify and select the most appropriate tools for
      measuring treatment compliance and appropriateness in multiple-disease patients,
      as well as the best reconciliation strategy. METHODS: The study used the Delphi
      methodology. We identified compliance and appropriateness questionnaires and
      scales, as well as functional organisation models for reconciliation that had
      been used in patients with multiple chronic conditions. Based on the strength of
      the evidence, their usefulness in these patients and ease of use, the panel
      selected the most appropriate ones. RESULTS: We selected 46 indications for the
      panel: 5 on compliance, 20 on appropriateness, and 31 on reconciliation. The tool
      considered most appropriate and with a high degree of agreement was the
      "Adherence to Refills and Medication Scale" questionnaire. For appropriateness,
      the Medication Appropriateness Index questionnaire was considered appropriate.
      The STOPP/START criteria were the most appropriate. The greatest degree of
      agreement regarding reconciliation was on the information that needed to be
      collected and the variables considered as discrepancies. CONCLUSIONS: The
      "Adherence to Refills and Medication Scale" questionnaire for compliance, the
      STOPP/START criteria, the Medication Appropriateness Index questionnaire for
      appropriateness and the development of a specific strategy for reconciliation
      were considered appropriate for the assessment of drug therapy in patients with
      multiple chronic conditions.

PMID- 22863427
TI  - Five-year survival and prognostic factors in a cohort of hospitalized
      nonagenarians.
AB  - BACKGROUND: The number of hospitalized nonagenarians is increasing. Only a few
      studies have evaluated long-term predictors of survival in these patients. The
      aim of this study was to determine the 5-year outcome of a cohort of hospitalized
      nonagenarians, and to identify predictors of long-term survival. METHODS: In 124
      consecutive medical hospitalized patients older than 89 years, and followed up
      during 5 years, the following variables were prospectively recorded:
      sociodemographic characteristics, main diagnoses, Charlson comorbidity index,
      Barthel index, Lawton-Brody test, Mini-Mental State Examination, Short Portable
      Mental Status Questionnaire of Pfeiffer, Mini Nutritional Assessment, albumin
      levels, and the 5-year survival. RESULTS: Out of the 124 patients, 109 died
      (87.9%) during the follow-up. The probability of being alive at 1, 3 and 5 years
      was 45%, 22% and 12%, respectively. A worse 5-year survival was significantly
      related to the diagnoses of pneumonia (p=0.037), heart failure (p=0.045), higher
      Charlson index (p=0.026), poorer functional status measured by the Barthel index
      (p=0.003), and the Lawton-Brody test (p=0.007), cognitive impairment measured by
      the Pfeiffer test (p=0.011), and lower levels of albumin (p=0.028). In the
      multivariate analysis, the Charlson index (p<0.001), and the Barthel index
      (p=0.003) were independently related to 5-year survival. These two variables were
      also 5-year survival prognostic factors in the subgroup of discharged patients. A
      prognostic index using these two variables was created: PI=(0.2 * Charlson index
      + 0.6 * Barthel index) * 0.92. CONCLUSIONS: In hospitalized nonagenarian
      patients, poor scores in the Barthel Index and a higher comorbidity evaluated by
      the Charlson index are independently related to 5-year survival.

PMID- 22863428
TI  - Predictors of survival within 2 years of inpatient rehabilitation among older
      adults.
AB  - BACKGROUND: Restoring functional independence in elderly people with disabilities
      is one of the main purposes of a geriatric rehabilitation unit. However, the
      rehabilitation period may also represent a useful circumstance to identify
      predictors of long-term health outcomes. The aim of this study was to evaluate a
      broad spectrum of characteristics in geriatric patients admitted to a
      rehabilitation unit in order to identify possible predictors of long-term
      survival. METHODS: This cross-sectional and prospective study was carried out in
      an Evaluation and Rehabilitation unit in Northern Italy. 243 persons aged 65 or
      older were enrolled over a period of 12 months (2007-8) and followed for 2 years.
      Possible predictors of survival were identified among a large spectrum of
      demographic, clinical (Charlson Index, lab data), nutritional (Mini-Nutritional
      Short-Form, bio-impedance analysis), and respiratory (spirometry) features.
      Logistic regression models were used to evaluate the association between
      patients' characteristics and survival. RESULTS: 189 (86.3%) participants were
      alive after 2 years of follow-up. Younger age, better functional status at
      discharge, a lower Charlson Index score, higher hemoglobin and albumin values at
      discharge, lower basal fasting glucose, creatinine, TNF-alpha levels, and extra
      cellular water, as well as higher cholesterol, vital capacity (VC), and
      inspiratory capacity were significantly associated with survival. In the
      multivariate model, higher VC (OR=6.2; 95%CI=1.6-24.6) and albumin (OR=3.7;
      95%CI=1.2-11.8) were associated with survival, whereas the Charlson Index and
      male gender showed an inverse correlation (OR=0.77; 95%CI=0.60-0.99 and OR=0.23;
      95%CI=0.10-0.95, respectively). CONCLUSION: VC was identified as one of the best
      predictors of survival along with higher albumin and lower Charlson Index score
      within 2 years of inpatient rehabilitation among older adults.

PMID- 22863429
TI  - Anaemia in the elderly: an aetiologic profile of a prospective cohort of 95
      hospitalised patients.
AB  - BACKGROUND AND OBJECTIVES: Anaemia is a significant problem in the elderly, and
      the cause of anaemia in approximately one third of the general population is
      unidentified. To date, only a few studies have focused on hospitalised patients.
      PATIENTS AND METHODS: We prospectively included anaemic patients (according to
      OMS criteria) aged 65 years and older who were hospitalised in the internal
      medicine department. The typical clinical data were collected, and a standardised
      set of biological tests, including cupraemia was performed. RESULTS: Of 360 total
      patients, 191 (53%) patients were anaemic; however, 96 patients were excluded
      because their data were incomplete. Of the remaining 95 patients that were
      included, 45 were men (47.4%) and 50 were women (52.6%); the mean patient age was
      79.7 years (66-101 years). At least one cause of anaemia was diagnosed in 87 of
      the 95 (91.6%) patients, and anaemia was multifactorial in 44 of the 95 (46.3%)
      cases. The five most prominent causes of anaemia were inflammation (62.1%), iron
      deficiency (30.5%), folic acid deficiency (21%), chronic renal failure (17.9%)
      and cobalamin deficiency (11.6%). Microcytosis was present in only 27.5% of the
      patients who had an iron deficiency, and macrocytosis was present in only 7.4% of
      the patients who had a folic acid and/or cobalamin deficiency. The cause of
      anaemia could not be identified for 8 of the patients. The cupraemia was normal
      in all the patients. CONCLUSION: A predefined protocol for older hospitalised
      patients was ability to identify the aetiology of anaemia in 91.6% of the cases;
      strikingly, anaemia was frequently caused by more than one factor (43.5%).
      Diagnostic orientation based on the mean corpuscular volume does not appear to
      correlate with mean cellular volume profile. Finally, anaemia caused by an
      unknown aetiology is rare and copper deficiency was not documented in any case.

PMID- 22863430
TI  - Anemia--prevalence and risk factors in pregnancy.
AB  - BACKGROUND: To assess the prevalence of decreased iron stores and anemia in
      pregnant women. To determine whether the risk factors: socio-demographic
      background, age, BMI, and parity are associated with abnormal hemoglobin
      concentrations and/or abnormal iron status. METHODS: A longitudinal study was
      carried out at the Department of Obstetrics, University Hospital of Zurich to
      establish the risk factors and prevalence of the decreased iron stores and anemia
      in early pregnancy. In order to determine the hematological parameters and
      ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and
      20 pregnancy weeks were collected. According to hemoglobin and iron status, the
      patients were divided into four groups: patients with iron deficiency anemia,
      patients with decreased iron stores, patients with anemia for other reasons and
      normal patients. The determinants socio-demographic background, age, BMI and
      parity were explored using multiple logistic regression analysis. RESULTS: The
      prevalence of decreased iron stores (ferritin<20 MUg/l) was observed in 31.8% of
      subjects (149/470) and anemia (Hb<110 g/l) in 18.5% (87/470). The prevalence of
      iron deficiency anemia was higher among women coming from former Yugoslavia and
      developing countries (p=0.004 and p=0.012). In patients coming from developing
      countries, a significant increase of anemia for other reasons was observed
      (p=0.027) and in patients older than 30 years, a significant increase of
      decreased iron stores (p=0.018). CONCLUSIONS: In our study population with low
      parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2%
      (236/470), and socio-demographic background was the most important risk factor of
      anemia.

PMID- 22863431
TI  - Geriatric assessment and chronic kidney disease in the oldest old: the Octabaix
      study.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) in older people is
      increasing. We determine the proportion of CKD in a sample of 321, 85-year-old
      community-dwelling subjects, and assess the association of socio-demographic
      data, global geriatric assessment data and comorbidity with CKD according to the
      estimated glomerular filtration rate (eGFR) of subjects. METHODS: Serum
      creatinine, eGFR (derived in ml/min/1.73 m(2) using the Modification of Diet in
      Renal Disease formula), socio-demographic 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 and prevalent chronic diseases were collected. RESULTS: CKD prevalence
      was 56.7% for eGFR < 60 ml/min/1.73 m(2), 19.9% for eGFR < 45 ml/min/1.73 m(2)
      and 6.6% for GFR < 30 ml/min/1.73 m(2). Multiple logistic regression analysis
      showed that a prior diagnosis of hypertension was associated with an eGFR < 60
      ml/min/1.73 m(2) (p<0.008, OR 2.134, 95% CI 1.216-3.744). A diagnosis of heart
      failure (p<0.001, OR 3.610, 95% CI 1.677-7.771) and a poor score on the quality
      of life measure (p<0.008, OR 0.9660, 95% CI 0.966-0.995) were associated with an
      eGFR < 45 ml/min/1.73 m(2). CONCLUSIONS: More than half of the oldest old in this
      study had an eGFR < 60 ml/min/1.73 m(2). A history of hypertension was associated
      with CKD. The group of patients with an eGFR < 45 ml/min/1.73 m(2) was associated
      with a diagnosis of heart failure and a worse quality of life.

PMID- 22863432
TI  - Brain natriuretic peptide is related to carotid plaques and predicts
      atherosclerosis in pre-dialysis patients with chronic kidney disease.
AB  - BACKGROUND: Although brain natriuretic peptide (BNP) concentration has been
      associated with atherosclerosis and ischemic cardiovascular diseases (CVD) in the
      general population, less is known about this relationship in pre-dialysis chronic
      kidney disease (CKD) patients. METHODS: We prospectively analyzed 227 pre
      dialysis patients with CKD [median estimated glomerular filtration rate (eGFR):
      28.82 (11.65-48.20) ml/min/1.73 m(2)]. At enrollment, BNP concentrations,
      biochemical and echocardiographic parameters were measured, and carotid artery
      ultrasound was performed. Patients were prospectively followed for a mean 31.8
      months (range 0.5-57.0 months). Ischemic CV events and patient outcomes were
      recorded. RESULTS: Median BNP concentration at enrollment was significantly
      higher in the CKD patients than in a control group [53.9 (16.2-181.0) pg/ml vs.
      9.4 (7.0-15.3) pg/ml, P<0.01]. BNP concentration was positively related with the
      carotid intima-media thickness of the common carotid artery (CCA-IMT) and left
      ventricular mass index (LVMI) and was significantly higher in patients with than
      without carotid plaques (P<0.01). Logistic regression analysis confirmed that
      lgBNP concentration was independently correlated with carotid plaques. Thirty-two
      patients experienced ischemic cardiovascular (ICV) events during follow-up.
      Kaplan-Meier analysis showed that cumulative survival without new ICV events was
      better in patients with lower than with higher BNP concentrations (P<0.01). Cox
      regression analysis showed that BNP was an independent risk factor for ICV events
      (HR=3.167, 95%CI=1.398-7.171, P<0.01). CONCLUSIONS: Similar to findings in the
      general population, elevated BNP level is related to atherosclerosis and an
      increased risk of ICV events in pre-dialytic CKD patients.

PMID- 22863433
TI  - Thrombotic biomarkers and left ventricle characteristics as short-term predictors
      of thrombotic events in patients hospitalized for acute decompensated heart
      failure.
AB  - BACKGROUND: Hospitalized acute decompensated heart failure (ADHF) patients have
      high risk of thromboembolic events (TE). The aim of this study is to determine
      the short-term prognostic value of TE for different thrombotic biomarkers
      (fibrinogen; D-dimer; tissue plasminogen activator antigen, t-PA; and plasminogen
      activator inhibitor type 1 antigen, PAI-1) and left ventricle echocardiographic
      characteristics (diastolic diameter, LVDD; ejection fraction, LVEF) in admitted
      ADHF patients. METHODS AND RESULTS: We included 140 patients with ADHF in NYHA
      classes III-IV (October 2009 to November 2011). Subjects with anticoagulant
      drugs, arrhythmias, or thrombosis were excluded. Biochemical and
      echocardiographic data were obtained within 12h after admission and all patients
      were given enoxaparin 40 mg/day. Throughout hospitalization (median, 11 days), 14
      subjects (10.0%) with ADHF received a TE diagnosis. Pulmonary embolism (PE,
      5.0%), deep-vein thrombosis (DVT, 7.1%), or a combination of these were confirmed
      in 3, 6 and 4 patients respectively. Cardioembolic stroke was diagnosed in 1
      subject (0.7%) associated with left ventricular intracavitary thrombus developed
      after admission. The following determinations most strongly predicted the short
      term risk of TE: fibrinogen>500 mg/dL (Odds Ratio [OR] 6.19; p=.0019), D
      dimer>600 ng/dL (OR 7.84; p=.0009), t-PA>10 ng/dL (OR 7.22; p=.0007), PAI-1>30
      ng/dL (OR 8.70; p<.0006), LVDD>50mm (OR 5.67; p=.0039), and LVEF<30% (OR 5.48;
      p=.0163). CONCLUSIONS: Elevated levels of fibrinogen, D-dimer, t-PA and PAI-1
      antigens as well as a dilated left ventricle with poor systolic function
      determined at admission are associated with a significantly high short-term risk
      of TE.

PMID- 22863434
TI  - The coexistence of heart failure predicts short term mortality, but not
      disability, in patients with acute ischemic stroke treated with thrombolysis: the
      Florence area Registry.
AB  - BACKGROUND: Thrombolysis in ischemic stroke reduces disability but not mortality.
      Our aim was to evaluate the predictivity of heart failure (HF) diagnosis on 90
      day mortality and disability in stroke patients undergoing thrombolysis. MATERIAL
      AND METHODS: Hospital records of all consecutive stroke patients treated with
      thrombolysis at our University Hospital were reviewed. Clinical assessment for HF
      and echocardiogram were available for all patients according to the thrombolysis
      institutional protocol. History of HF, LVEF <40%, or BOSTON score >= 5 were
      tested as predictors. RESULTS: Of 130 patients (age 66 +/- 14 years, 64.6% males,
      baseline NIHSS 15.6 +/- 8.8), 17 (13.1%) had a history of HF, 16 (12.7%) a BOSTON
      score >= 5, 13 (10.9%) a LVEF <40% and 24 (19.0%) met clinical criteria for HF
      diagnosis. Ninety-day mortality and incidence of disability were 16.1% and 36.1%,
      respectively. After adjustment for age, sex, baseline stroke severity and pre
      stroke disability, LVEF <40% and clinical diagnosis of HF were predictors of 90
      day mortality, (p=0.007 and p=0.037, respectively). CONCLUSION: Clinical
      diagnosis of HF predicts mortality, but not disability, in acute stroke patients
      undergoing thrombolysis. Unlike anamnestic record of HF, clinical evaluation of
      cardiac function, with estimation of LVEF, predicts mortality.

PMID- 22863435
TI  - Metabolic syndrome and vascular risk estimation in a Mediterranean non-diabetic
      population without cardiovascular disease.
AB  - AIMS: Vascular risk equations are tools used to help prevent cardiovascular
      events. Our aim was to compare the REGICOR and SCORE equations in a general
      population and in persons with the metabolic syndrome (MS) according to the
      criteria of the International Diabetes Federation. METHODS AND RESULTS: We
      calculated the cardiovascular risk with both equations in a random sample of 838
      non-diabetic persons aged 40-65years without a history of cardiovascular disease,
      of whom 251 had the MS. Of the 838 persons, 3.6% had a high risk according to
      SCORE and 1.5% according to REGICOR, and of these, 53.3% and 61.5%, respectively,
      had the MS. The mean risk was greater in the persons with the MS than those
      without (REGICOR 4.6% vs. 2.6% and SCORE 1.7% vs. 1%; p<0.01 for each). In
      comparison with the group without the MS, the percentage of persons with the MS
      who had a high risk was greater with both scales: REGICOR (3.2% vs. 0.8%,
      p=0.027) and SCORE (6.4% vs. 2.4%, p=0.004). The agreement (kappa index)
      classifying the subjects with a high risk, was 0.453 in the overall sample and
      0.391 in the subgroup with the MS. CONCLUSIONS: The percentage of persons
      classified as having a high cardiovascular risk differed between REGICOR and
      SCORE. Using these scales only a small percentage of non-diabetic persons with
      the MS have a high risk. The presence of the MS multiplies the percentage of non
      diabetic persons with a high vascular risk two-fold with SCORE and four-fold with
      REGICOR.

PMID- 22863436
TI  - Intensive versus conventional glucose control in critically ill patients: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Critically ill patients commonly develop hyperglycemia. It remains
      unclear, however, to what extent correcting hyperglycemia will benefit these
      patients. We performed this meta-analysis to evaluate the benefits and risks of
      intensive glucose control versus conventional glucose control in critically ill
      adult patients. METHODS: A systematic literature search of MEDLINE, PubMed, and
      Cochrane databases (until June 2011) was conducted using specific search terms.
      Randomized controlled trials that compared intensive glucose control with a
      target glucose goal <6.1 mmol/l (110 mg/dl) to conventional glucose control in
      adult intensive care patients were included. The random-effect model was used to
      estimate the pooled risk ratio of the two treatment arms. RESULTS: Twenty two
      studies that randomized 13,978 participants were included in the meta-analysis.
      Overall, intensive glucose control did not reduce the short-term mortality
      (RR=1.02, 95% CI: 0.95-1.10, p=0.51), 90 day or 180 day mortality (RR=1.06, 95%
      CI: 0.99-1.13, p=0.08), sepsis (RR=0.96, 95% CI: 0.83-1.12, p=0.59) or new need
      for dialysis (RR=0.96, 95% CI: 0.83-1.11, p=0.57). The incidence of hypoglycemia
      was significantly higher in intensive glucose control group compared with
      conventional glucose control group (RR=5.01, 95% CI: 3.45-7.28, p<0.00001).
      CONCLUSIONS: This meta-analysis found that intensive glucose control in
      critically ill adults did not reduce mortality but is associated with a
      significantly increased risk of hypoglycemia.

PMID- 22863437
TI  - Association between leptin and its soluble receptor with cardiometabolic risk
      factors in a Brazilian population.
AB  - BACKGROUND: Most studies evaluating the conjoint effects of leptin and human
      soluble leptin receptor (hs-LR) on cardiometabolic risk factors have been
      conducted in well-characterized ethnic groups. We aimed to assess the
      associations of leptin and hs-LR with the cardiometabolic risk factors that
      reflect the components of metabolic syndrome (MetS) in a Brazilian population
      with varying degrees of adiposity. METHODS: This is a cross-sectional analysis of
      adult subjects (n=173, age 45 +/- 12 years, 124 women; body mass index [BMI] 35.6
      +/- 9.5 kg/m(2)) for association of leptin and its soluble receptor with
      cardiometabolic risk factors (glucose, BMI, waist circumference, hip
      circumference, blood pressure, insulin, cholesterol and triglycerides). Plasma hs
      LR was measured by ELISA; insulin and leptin were determined by RIA. Metabolic
      syndrome was defined by NCEP/ATP III. RESULTS: Leptin was positively associated
      with blood pressure, BMI, waist circumference, hip circumference, triglycerides,
      glucose, insulin and HOMA and inversely correlated with HDL-cholesterol. The hs
      LR exhibited inverse relationship with cardiometabolic risk factors (P <= 0.006),
      except for glucose and lipid parameters. Leptin increased, whereas hs-LR
      decreased, with increasing number of MetS components (P for trend<0.001). In
      multivariable models, sex, BMI and insulin were independently associated with
      leptin, whereas age, sex, BMI and systolic blood pressure were the independent
      correlates of hs-LR. CONCLUSION: In a Brazilian population with complex
      interethnic admixture, levels of hs-LR and leptin were independently associated
      with systolic blood pressure and insulin, respectively. Leptin increased with
      increasing number of MetS components. In turn, hs-LR decreased as the number of
      MetS components increased.

PMID- 22863438
TI  - Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism.
AB  - BACKGROUND: The relationship between ischemia-modified albumin (IMA) and thyroid
      dysfunction remains uncertain. This study aimed to investigate the influence of
      overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on
      serum IMA levels. METHODS: A total of 35 untreated patients with Ohe, 35
      untreated patients with Oho, and 35 control subjects were enrolled in the study.
      C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were
      measured and evaluated before and after treatment. RESULTS: CRP, Hcy, and IMA
      levels and lipid profiles were higher in patients with Oho than in euthyroid or
      Ohe subjects (p<0.05). Basal IMA levels were reduced after treatments in all
      patients (p<0.05). In Ohe patients, serum IMA levels were positively correlated
      with free triiodothyronine (r=0.424, p=0.011) and free thyroxine (r=0.567,
      p<0.001) levels. In Oho patients, serum IMA levels were inversely correlated with
      free triiodothyronine (r=-0.555, p=0.001) and free thyroxine (r=-0.457, p=0.006)
      but positively correlated with anti-thyroid peroxidase antibody, C-reactive
      protein, and homocysteine levels (p<0.05). Linear regression analyses showed that
      free triiodothyronine was the most important factor affecting serum IMA levels in
      Ohe (beta=0.694, p=0.019) and in Oho (beta=-0.512, p=0.025). CONCLUSIONS: IMA
      levels are increased in patients with thyroid dysfunction, particularly in overt
      hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative
      stress status.

PMID- 22863439
TI  - Postprandial hyperlipidemia in overt and subclinical hypothyroidism.
AB  - BACKGROUND AND AIMS: Lipid alterations in overt hypothyroidism (OH) were well
      known, but its changes in subclinical hypothyroidism (SCH) and postprandial
      period were not clear. The aim of this study is to evaluate postprandial lipemia
      by oral lipid tolerance test (OLTT) in patients with OH and SCH. MATERIALS AND
      METHODOLOGY: Twenty-five OH and 27 SCH, totally 52 hypothyroid patients [mean age
      38.3 +/- 12.8 year, body mass index (BMI): 29.0 +/- 5.8 kg/m(2)] and 23 BMI- and
      age-matched healthy controls (mean age 36.7 +/- 11.9 years; BMI: 27.1 +/- 6.9
      kg/m(2)) were included to the study. Anthropometric measurements and HOMA-IR
      levels were measured. Basal and postprandial lipid profile at 2nd, 4th, 6th and
      8th hours were determined by oral lipid tolerance test. RESULTS: There were not
      any statistical differences among three groups (control, OH and SCH) in terms of
      mean fasting levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and
      triglyceride. On the contrary, mean triglyceride levels at postprandial 8th hour
      in both OH and SCH patients were higher than control subjects (p=0.017 and
      p=0.049, respectively). Again mean postprandial 8th hour VLDL-cholesterol levels
      in OH group were also higher than control subjects (p=0.05). In addition mean
      HOMA-IR value of SCH and OH patients was similar with control subjects (1.5 +/-
      1.4 in OH; 1.3 +/- 0.8 in SCH; 2.2 +/- 2.2 in control group). CONCLUSIONS:
      Although total, LDL and VLDL-cholesterol, and triglyceride levels were not
      different from healthy controls, triglyceride and/or VLDL-cholesterol levels
      apparently increased with OLTT in both OH and SCH patients. Decreased lipid
      clearance may be responsible for this result.

PMID- 22863440
TI  - Historical study of acute hepatitis B in subjects with or without hepatitis C
      infection.
AB  - BACKGROUND: The epidemiological pattern of hepatitis B virus infection in Italy
      has greatly changed over the past decades. The aim of the study was to evaluate
      during time the epidemiological features of acute hepatitis B cases referred to
      an Infectious Disease Unit in North-East of Italy between 1978 and 1995. PATIENTS
      AND METHODS: Stored sera of 183 cases were tested for HBV markers, HBV genotypes,
      anti-Delta and anti-HCV. RESULTS: Anti-HBcIgM was positive in all cases. Mean age
      increased from 30.2 years in 1978 to 37.5 in 1995 (P<0.01). Significant increase
      was observed in proportion of cases reporting intravenous drug use from 11.5% to
      29.6% (P<0.03). Chronicity rate was as low as 1.1%. Mean days of hospitalization
      significantly decreased. HBV genotype determination showed that majority of cases
      was infected by genotype D, but its prevalence decreased from 88.2% in 1978 to
      75.0% in 1995. Delta coinfection was present in 8.2%. The prevalence of HCV in
      patients with acute HBV was 35.0%; it fluctuated from 26.2% to 44.2%, mostly
      related (53.1%) to intravenous drug use. Dual infection did not lead to a more
      severe course of disease. CONCLUSIONS: From this retrospective study, remarkable
      fluctuations in the prevalence of dual HBV-HCV infection before the
      implementation of HBV vaccination were observed. Presence of anti-HCV did not
      affect the course of acute HBV.

PMID- 22863441
TI  - Kayser-Fleischer ring in Wilson's disease: a cohort study.
AB  - AIMS: To evaluate Wilson's disease (WD) features in Sardinian patients with
      Kayser-Fleischer (KF) ring and to evaluate correlations between modifications in
      KF and anti-copper therapy and systemic WD evolution. PATIENTS AND METHODS: Sixty
      seven WD patients (35 m/32 f; mean age 41 years) were retrospectively studied. At
      diagnosis and during follow up comprehensive ophthalmologic and neurologic
      examinations, brain RMN and ECD SPECT, detailed objective laboratory studies and
      hepatic histological examination were performed on all patients for analysis. All
      patients were given anti-copper therapy with d-Penicillamine in mono-therapy or
      in combination with Zinc Salts. RESULTS: At diagnosis, KF was observed in 27% of
      patients with equal distribution in all age groups. Significant correlations
      between KF at diagnosis, neuro-psychiatric manifestations and pathologic features
      in brain RMN and in brain ECD SPECT were found at diagnosis. During follow up, a
      decrease in, or regression of KF was seen in 14% of patients. Anti-copper therapy
      leads to KF regression and prevents the appearance of KF. No significant
      correlations were observed between KF regression and clinical neurological or
      neuro-imaging improvement nor between KF modifications and clinical hepatic
      improvement. CONCLUSIONS: Our study highlights the peculiar features of Sardinian
      WD patients: low representation of KF, its equal distribution in all age groups,
      significant correlation between KF at diagnosis and clinical neurological
      manifestations, pathologic brain RMN and brain ECD-SPECT are highlighted by our
      study. Anti-copper therapy induces KF regression and prevents its onset.
      Therefore, KF ring does appear to be a predictive factor in the neurological and
      hepatic evolution of WD.

PMID- 22863442
TI  - Insulin-like growth factor-II is a useful marker to detect hepatocellular
      carcinoma?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The
      utility of serum alpha-fetoprotein (alpha-FP) in its detection is questionable.
      Over-expression and high circulating levels of insulin-like growth factor-II (IGF
      II) were reported in tissue and in serum of patients with HCC. We investigated
      the diagnostic application of IGF-II in the diagnosis of HCC. METHODS: Serum IGF
      II and alpha-FP levels were measured in 178 patients (82 with HCC and 96 with
      liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric
      combination test and confidence interval analysis were used for statistical
      evaluation of data. RESULTS: The best cut-off values selected by ROC curves were
      796 ng/ml for IGF-II and 132 ng/ml for alpha-FP. IGF-II mean values were higher
      in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower
      in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found
      in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of
      controls. alpha-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1%
      of LC and in none of control group. By correlation study, serum IGF-II levels
      were significantly correlated with serum alpha-FP levels (r=0.427, p=0.0001) and
      with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number
      (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive
      values than alpha-FP. CONCLUSION: Circulating IGF-II is not a useful marker for
      HCC. Further researches are however needed to evaluate its diagnostic accuracy
      before and after nutritional adjustment.

PMID- 22863443
TI  - Adverse drug reactions as the cause of emergency department admission of patients
      aged 80 years and older.

PMID- 22863444
TI  - Clinical and laboratory observations during refeeding after starvation in
      patients.

PMID- 22863445
TI  - Lymphocyte-suppressing effects of omega-3 fatty acids in bezafibrate-treated
      patients with isolated hypertriglyceridemia.

PMID- 22863446
TI  - Hemostatic effects of omega-3 fatty acids in isolated hypertriglyceridemic
      patients treated with bezafibrate.

PMID- 22863447
TI  - Chemokine/chemokine receptor interactions contribute to the accumulation of Th17
      cells in patients with esophageal squamous cell carcinoma.
AB  - Chemokine/chemokine receptor interactions play a critical role in lymphocyte
      infiltration of tumors. Recent studies suggest that Th17 cells accumulate within
      many types of tumors, although the mechanisms that control this are unclear. We
      studied the distribution and phenotypic features of Th17 cells chemokine
      receptors, as well as the mRNA levels of CCL2, CCL17, CCL20, and CCL22 in tumors
      of patients with esophageal squamous cell carcinoma. We found that Th17 cells
      accumulated in tumors, and high expressions of CCR4, CCR6 were detected in Th17
      cells. Levels of the chemokines CCL17, CCL20, and CCL22 in tumors were
      significantly higher than in tumor-free tissues, and were positively correlated
      with the distribution of Th17 cells in tumors. Furthermore, an in vitro migration
      assay showed that CCL17, CCL20 and CCL22 had chemotactic effects on tumor-derived
      Th17 cells. In conclusion, the CCR4-CCL17/22 and CCR6-CCL20 axis might play an
      important role in Th17 cell infiltration of tumors.

PMID- 22863448
TI  - Endothelial molecules decipher the mechanisms and functional pathways in antibody
      mediated rejection.
AB  - Microvascular endothelium is the main target of injury in antibody-mediated
      rejection of human organ transplants. Hence, antibody-mediated rejection
      histologically presents with microvascular inflammation (pulmonary or myocardial
      or peritubular capillaritis, glomerulitis), thrombosis, and endothelial
      remodeling (duplication and/or multilayering of glomerular and capillary basement
      membranes). We previously observed upregulation of several endothelial genes in
      kidney transplant biopsies from patients with donor specific antibodies,
      indicating active antibody-mediated rejection and poor graft survival.
      Furthermore, endothelial molecular signals discovered a previously unknown
      clinical phenotype: C4d negative antibody-mediated rejection. With the
      recognition of C4d negative antibody-mediated rejection, data from multiple
      transplant centers now show that antibody-mediated rejection is the most common
      cause of late kidney transplant failure. This paper reviews the current
      understanding of endothelial cell biology in antibody-mediated rejection,
      emphasizing recent advances and pending questions. Furthermore, the paper
      discusses functionally active pathways in human antibody-mediated rejection,
      which include aspects of endothelial activation with increased endothelial
      adhesive and pro-coagulant signals facilitating leukocyte trafficking and
      attachment, cell-to-basement membrane interactions, platelet activation,
      coagulation, and endothelial repair responses. To understand effector mechanisms
      of antibody-mediated rejection and quantify the degree of antibody-mediated
      tissue injury in clinical transplants, endothelial cells provide a useful read
      out.

PMID- 22863449
TI  - Detection of natural and induced phenoloxidase activities in human serum.
AB  - Natural and induced phenoloxidase activities were detected in human serum using
      nine different phenolic substrates, namely, tyrosine, tyramine, L-DOPA, DL-DOPA,
      dopamine, catechol, hydroquinone, protocatechuic acid and pyrogallol.
      Phenoloxidase activity was induced anew in serum using exogenous elicitors, such
      as proteases or detergents. Among the proteases and detergents tested, pronase,
      SDS and Tween 20 were the best elicitors of phenoloxidase activities in serum,
      wherein, hydroquinone was the best phenolic substrate for both untreated as well
      as pronase treated serum and SDS or Tween 20 treated serum resulted in highest
      oxidation of dopamine or tyrosine, respectively. In the present study, all these
      oxidative reactions were inhibited by phenoloxidase inhibitors, namely, PTU and
      tropolone, thereby, confirming the role of phenoloxidase in human serum.

PMID- 22863450
TI  - Did I turn off the stove? Good inhibitory control can protect from influences of
      repeated checking.
AB  - BACKGROUND AND OBJECTIVES: Obsessive-compulsive disorder (OCD) is an anxiety
      disorder characterized by compulsions aimed at reducing anxiety associated with
      intrusive cognitions. However, compulsive behaviors such as repeated checking
      were found to increase rather than decrease uncertainty related to obsessive
      thoughts (e.g., whether the gas stove was turned off). Some recent studies
      illustrate that OCD patients and their family members have inhibitory deficits,
      often demonstrated by the stop-signal task. The current study aims to investigate
      relations between inhibitory control and effects of repeated checking. METHODS:
      Fifty-five healthy participants carried out a stop-signal task followed by a
      repeated-checking task. Additionally, participants were asked to complete self
      report questionnaires measuring OCD, anxiety and depression symptoms. RESULTS:
      Confirming our hypothesis, participants with poor inhibitory capabilities
      demonstrated greater uncertainty and memory distrust as a consequence of repeated
      checking than participants with good inhibitory control. LIMITATIONS: Our
      findings concern an initial investigation on a sample of healthy participants and
      should be replicated and extended to clinical populations. CONCLUSIONS: These
      results suggest that deficits in inhibitory control may underlie cognitive
      vulnerability in OCD. An updated model integrating neuropsychological findings
      with current OCD models is suggested.

PMID- 22863451
TI  - Cambodian Bon Om Touk stampede highlights preventable tragedy.
AB  - The tragic nature of the human stampede that took place in Phnom Penh, Cambodia
      on November 22, 2010 claimed the lives of 347 people during the three-day-long
      Water Festival, known as Bon Om Touk. Described as the greatest tragedy that
      Cambodia has experienced since the collapse of the Khmer Rouge, the Bon Om Touk
      stampede ranks among the deadliest human stampede disasters during the past 30
      years, a Class IV event exceeding 100 fatalities according to a recently proposed
      scale. 1 From the perspective of global health, the event shares many
      characteristics with preceding major crowd disasters and failures in event
      planning. It is essential for the international community to officially monitor
      human stampedes as it does other major disasters. Additional research on human
      stampedes is needed to improve our collective understanding of the causes of
      crowd disasters and how best to prevent them. Hsu EB , Burkle FM Jr . Cambodian
      Bon Om Touk stampede highlights preventable tragedy.

PMID- 22863453
TI  - Discovery and innovation: the (atomic) clock is ticking.

PMID- 22863452
TI  - Adsorption of beta-galactosidase of Alicyclobacillus acidocaldarius on wild type
      and mutants spores of Bacillus subtilis.
AB  - BACKGROUND: The Bacillus subtilis spore has long been used as a surface display
      system with potential applications in a variety of fields ranging from mucosal
      vaccine delivery, bioremediation and biocatalyst development. More recently, a
      non-recombinant approach of spore display has been proposed and heterologous
      proteins adsorbed on the spore surface. We used the well-characterized beta
      galactosidase from the thermoacidophilic bacterium Alicyclobacillus
      acidocaldarius as a model to study enzyme adsorption, to analyze whether and how
      spore-adsorption affects the properties of the enzyme and to improve the
      efficiency of the process. RESULTS: We report that purified beta-galactosidase
      molecules were adsorbed to purified spores of a wild type strain of B. subtilis
      retaining ca. 50% of their enzymatic activity. Optimal pH and temperature of the
      enzyme were not altered by the presence of the spore, that protected the adsorbed
      beta-galactosidase from exposure to acidic pH conditions. A collection of mutant
      strains of B. subtilis lacking a single or several spore coat proteins was
      compared to the isogenic parental strain for the adsorption efficiency. Mutants
      with an altered outermost spore layer (crust) were able to adsorb 60-80% of the
      enzyme, while mutants with a severely altered or totally lacking outer coat
      adsorbed 100% of the beta-galactosidase molecules present in the adsorption
      reaction. CONCLUSION: Our results indicate that the spore surface structures, the
      crust and the outer coat layer, have an negative effect on the adhesion of the
      beta-galactosidase. Electrostatic forces, previously suggested as main
      determinants of spore adsorption, do not seem to play an essential role in the
      spore-beta-galactosidase interaction. The analysis of mutants with altered spore
      surface has shown that the process of spore adsorption can be improved and has
      suggested that such improvement has to be based on a better understanding of the
      spore surface structure. Although the molecular details of spore adsorption have
      not been fully elucidated, the efficiency of the process and the pH-stability of
      the adsorbed molecules, together with the well documented robustness and safety
      of spores of B. subtilis, propose the spore as a novel, non-recombinant system
      for enzyme display.

PMID- 22863454
TI  - The kindness of strangers.

PMID- 22863455
TI  - The loneliness of the long-distance radiologist.

PMID- 22863456
TI  - Radiology and primary care.

PMID- 22863457
TI  - Point: Generalism vs subspecialization--the ACR should encourage radiologists to
      structure their practices around a model of subspecialization.

PMID- 22863458
TI  - Counterpoint: Generalism vs subspecialization--the ACR should develop a practice
      model to support general radiologists.

PMID- 22863459
TI  - Medicare quality and resource use reports: crunching data or crushing data.

PMID- 22863460
TI  - Gaming the boards.

PMID- 22863461
TI  - IT tools can help "harvest" clinical case material from your PACS.

PMID- 22863462
TI  - ACR Appropriateness Criteria(r) limping child--ages 0 to 5 years.
AB  - The appropriate imaging for pediatric patients (ages 0-5 years) being evaluated
      for limping depends on the clinical presentation, specifically, the presence of
      signs of infection, any localization of pain, and history of or suspected trauma.
      Common diagnoses causing limping in children are briefly reviewed, and
      recommended imaging techniques are discussed, including toddler's fracture,
      transient synovitis, septic arthritis, Legg-Calve-Perthes disease, and
      osteomyelitis. 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- 22863463
TI  - The general radiologist in the 21st century.
AB  - An ACR task force investigated the changing roles of general and subspecialized
      radiologists in current academic and private practice settings. The task force
      considered historical factors that influenced the evolution of current practice
      models and evaluated recent socioeconomic trends that will influence the future
      of radiology practices. The task force proposes a new model of multispecialty
      radiologists as an exciting and viable option to help build robust future
      academic and private radiology practices.

PMID- 22863464
TI  - Proton facility economics: the importance of "simple" treatments.
AB  - PURPOSE: Given the cost and debt incurred to build a modern proton facility,
      impetus exists to minimize treatment of patients with complex setups because of
      their slower throughput. The aim of this study was to determine how many "simple"
      cases are necessary given different patient loads simply to recoup construction
      costs and debt service, without beginning to cover salaries, utilities, beam
      costs, and so on. Simple cases are ones that can be performed quickly because of
      an easy setup for the patient or because the patient is to receive treatment to
      just one or two fields. METHODS: A "standard" construction cost and debt for 1,
      3, and 4 gantry facilities were calculated from public documents of facilities
      built in the United States, with 100% of the construction funded through standard
      15-year financing at 5% interest. Clinical best case (that each room was
      completely scheduled with patients over a 14-hour workday) was assumed, and a
      statistical analysis was modeled with debt, case mix, and payer mix moving
      independently. Treatment times and reimbursement data from the investigators'
      facility for varying complexities of patients were extrapolated for varying
      numbers treated daily. Revenue assumptions of $X per treatment were assumed both
      for pediatric cases (a mix of Medicaid and private payer) and state Medicare
      simple case rates. Private payer reimbursement averages $1.75X per treatment. The
      number of simple patients required daily to cover construction and debt service
      costs was then derived. RESULTS: A single gantry treating only complex or
      pediatric patients would need to apply 85% of its treatment slots simply to
      service debt. However, that same room could cover its debt treating 4 hours of
      simple patients, thus opening more slots for complex and pediatric patients. A 3
      gantry facility treating only complex and pediatric cases would not have enough
      treatment slots to recoup construction and debt service costs at all. For a 4
      gantry center, focusing on complex and pediatric cases alone, there would not be
      enough treatment slots to cover even 60% of debt service. Personnel and recurring
      costs and profit further reduce the business case for performing more complex
      patients. CONCLUSIONS: Debt is not variable with capacity. Absent philanthropy,
      financing a modern proton center requires treating a case load emphasizing simple
      patients even before operating costs and any profit are achieved.

PMID- 22863465
TI  - The role of the VA in academic radiology: a report of the ACR's Committee on
      Governmental and Regulatory Affairs in Academic Radiology.
AB  - Academic radiology departments have benefited from their relationships with US
      Department of Veterans Affairs hospitals. Review of the history of the care of
      veterans shows a unique relationship with academic medical centers. Opportunities
      for future collaborations include clinical care, teaching, and research.

PMID- 22863466
TI  - Breast cancer in Pakistan: identifying local beliefs and knowledge.
AB  - PURPOSE: The aim of this study was to assess the attitudes of women and general
      practitioners (GPs) living in Karachi, Pakistan, regarding breast cancer,
      mammographic screening, and local barriers to breast health care. METHODS: This
      study was performed using questionnaires designed specifically for women and for
      GPs in Karachi. Geographically dispersed collaborators identified GPs from
      neighborhoods across Karachi; snowball sampling located additional GPs and women
      in neighboring areas. Trained local community health workers conducted one-on-one
      surveys and used specially equipped (openXdata) mobile phones to enter and upload
      participant responses in real time. RESULTS: The survey included 200 women
      (median age, 35 years; range, 24-63 years), and 100 GPs (49% men, 51% women).
      Women's knowledge of breast cancer incidence, diagnosis, and treatment was
      proportionate to educational level, while willingness to address breast health
      issues and interest in early detection were high regardless of education level.
      Very few women had ever undergone clinical breast examinations (16%) or
      mammography (9%). Among GPs (median time practicing, 12 years; range, 1-40
      years), most understood major risk factors and importance of early detection.
      However, 20% did not believe breast cancer occurs in Pakistan, and 30% believed
      that it is a fatal disease. Female GPs were more likely to perform clinical
      breast examinations (98%) than male GPs (24%). CONCLUSIONS: This study has
      identified specific areas to target for educational and early detection programs.
      Women need more awareness and access to routine examinations and mammography; GPs
      need more education regarding the incidence and management of breast cancer. Male
      GPs would benefit from having trained female assistants to perform clinical
      breast examinations.

PMID- 22863467
TI  - Comparison of dual-syringe and syringeless power injectors in outpatient MDCT
      practice: impact on the operator's performance, CT workflow, and operation cost.
AB  - PURPOSE: The purpose of this study was to compare enhancement quality,
      performance efficiency, technologists' satisfaction, and operation costs between
      2 different power injectors (PIs) in an outpatient setting. METHODS: In this
      prospective study, 275 consecutive outpatients (135 men, 140 women) scheduled for
      contrast-enhanced CT (CECT) were randomized and scanned using either of 2
      multidetector CT scanners (16 adjacently placed detectors) fitted with a dual
      syringe contrast injector or a syringeless contrast injector. The corresponding
      CECT studies were subjectively reviewed by 2 radiologists in consensus to rate
      the quality of contrast enhancement in each study. The equipment preparation time
      (contrast media [CM], saline loading), releasing time (unloading of saline and
      CM), and CM wastage incurred for each PI were recorded by one operator.
      Technologists' satisfaction with the use of the PIs was rated on a 10-point
      scale. Statistical analyses were performed using Student's t tests. RESULTS: A
      total of 140 patients were examined using the dual-syringe system, and 135 with
      the syringeless system, and CECT examination quality was comparable for both PI
      systems (P > .05). Equipment preparation time and releasing time per examination
      for dual-syringe and syringeless PIs were 139 +/- 39 and 32 +/- 14 seconds and 48
      +/- 31 and 8 +/- 3 seconds, respectively (P < .001). On average, 11 mL CM wastage
      per examination was observed with the dual-syringe PI and 0 mL with the
      syringeless PI (P < .001). Technologists had higher satisfaction with the
      syringeless PI than the dual-syringe system (9.3 vs 6.3, P < .01). Because of
      improved efficiency, 2.6 additional patients per day were examined in the room
      using the syringeless PI. CONCLUSION: Given comparable CECT examination quality,
      the syringeless PI was more user-friendly and improved outpatient CT workflow and
      CT throughput while allowing 11-mL CM saving per examination compared with the
      dual-syringe injector.

PMID- 22863468
TI  - Mitigating the risks: tips for contracting with teleradiologists.

PMID- 22863469
TI  - Functions of the quality committee in radiology.

PMID- 22863470
TI  - Bring in the negotiator: the basics of the art of negotiations.

PMID- 22863471
TI  - Interpretation of outside imaging studies: solutions from a tertiary care trauma
      center.

PMID- 22863472
TI  - Radiation dose measurements and monitoring for fluoroscopically guided
      interventional procedures.

PMID- 22863473
TI  - Culture: the character of an institution.

PMID- 22863474
TI  - Jack Campbell.

PMID- 22863475
TI  - Re: "Call for action: a resident's perspective".

PMID- 22863476
TI  - Encoding the world around us: motor-related processing influences verbal memory.
AB  - It is known that properties of words such as their imageability can influence our
      ability to remember those words. However, it is not known if other object-related
      properties can also influence our memory. In this study we asked whether a word
      representing a concrete object that can be functionally interacted with (i.e.,
      high-manipulability word) would enhance the memory representations for that item
      compared to a word representing a less manipulable object (i.e., low
      manipulability word). Here participants incidentally encoded high-manipulability
      (e.g., CAMERA) and low-manipulability words (e.g., TABLE) while making word
      judgments. Using a between-subjects design, we varied the depth-of-processing
      involved in the word judgment task: participants judged the words based on
      personal experience (deep/elaborative processing), word length (shallow), or
      functionality (intermediate). Participants were able to remember high
      manipulability words better than low-manipulability words in both the personal
      experience and word length groups; thus presenting the first evidence that
      manipulability can influence memory. However, we observed better memory for low-
      than high-manipulability words in the functionality group. We explain this
      surprising interaction between manipulability and memory as being mediated by
      automatic vs. controlled motor-related cognition.

PMID- 22863477
TI  - Suppression of novel stimuli: changes in accessibility of suppressed
      nonverbalizable shapes.
AB  - Recently, a new method of considering successful intentional thought suppression
      has emerged. This method, the think/no-think (TNT) paradigm has been utilized
      over a multitude of settings and has fairly robustly demonstrated the ability to
      interfere with memory recall. The following experiment examined the effect of
      intentional thought suppression on recognition memory of nonverbalizeable shapes.
      In this experiment, participants learned word-shape targets. For some of the
      pairs, they rehearsed the shape when presented with the word; for others, they
      suppressed the shape when presented with the word. Finally, participants were
      shown multiple shapes, one at a time, and asked to identify which they had
      previously seen as paired with a word. Results of the experiment indicated that,
      similar to results involving words, participants were less accurate in
      identifying suppressed shapes, as compared to rehearsed shapes. Implications of
      these findings are discussed.

PMID- 22863478
TI  - Spatial differences within the membrana granulosa in the expression of focimatrix
      and steroidogenic capacity.
AB  - In the ovarian follicular membrana granulosa there are morphological and
      functional differences between cells adjacent to the follicular fluid lumen, or
      aligning the basal lamina. Amongst the observed functional differences are
      steroidogenic capacity and expression levels of a novel basal lamina, focimatrix;
      both of which increase in the later stages of antral follicle growth. A number of
      different studies have produced apparently inconsistent results as to which cell
      layers are more steroidogenic. To examine this systematically, individual bovine
      follicles, confirmed as healthy by post hoc histological examination, were used
      to isolate populations of apical and basal granulosa cells. Cell counts revealed
      that the respective groups did not differ in the numbers of cells, thus
      confirming the separation of these populations. We measured gene expression
      (quantitative RT-PCR, n=8-10, follicle diameter 14.0+/-0.5 mm) and protein levels
      (Western immunoblotting, n=14, follicle diameter 11.9+/-0.5 mm) and hormone
      production from granulosa cells (2.5*10(5) viable cells/well in serum-free
      conditions for 24 h, n=15, diameter 12+/-0.5 mm). Levels of mRNA of HSD3B1 and
      CYP19A1 and three focimatrix genes COL4A1, HSPG2 and LAMB2 and LHCGR were
      significantly lower in apical granulosa cells (P<0.05), whereas, expression of
      CYP11A1 and HSD17B1 were not different (P>0.05). The protein levels of
      steroidogenic enzymes P450scc and P450arom were significantly higher in apical
      cells (P<0.05), whereas those of 3beta-hydroxysteroid dehydrogenase and 17beta
      hydroxysteroid dehydrogenase type 1 were not different (P>0.05). Progesterone
      production was significantly lower and oestradiol production was significantly
      higher in apical granulosa cells (P<0.05). These results confirm that apical and
      basal cells are functionally different, and the differences might be explained by
      the location of cells of different ages and maturity within the membrana
      granulosa. Discrepancies in the literature on their steroidogenic capacity may
      reflect differences in the steroidogenic parameters measured.

PMID- 22863479
TI  - [Clinical and preventive intervention in eating behaviour: a dialogue between
      psychology and nutritional sciences].
AB  - The eating habits modification is a clinical challenge, both on therapeutic and
      preventive levels, which requires tools from various areas of health, such as
      psychology and nutrition. In the structured work in these areas, that includes
      the referral to specialist consultants, there is a need of a first intervention
      in Primary Health Care, in clinical and community levels. In this paper, we
      attempt to systematize useful information for intervention. We will start by
      reviewing some important interviewing skills, some models of motivational
      interviewing, and we will make a brief reflection about the client. Then we will
      analyse an individual case structured in two complementary levels of
      interpretation: a closer look in general factors and another that reflect the
      antecedents, consequences and the description of the behaviour problem. We will
      also tackle issues related to the context in which the individual moves. We will
      analyse some group intervention programs within a clinical and preventive
      perspectives. Finally, we will discuss some concepts related to therapeutic
      adherence.

PMID- 22863480
TI  - [The transoesophageal echocardiography in the general intensive care: its utility
      in the ventilated critically ill patient].
AB  - The use of the transoesophageal echocardiography (TEE) in the critically ill
      patient admitted to the general intensive care unit begins to turn out to be very
      important but it is still little spread. The full implementation of the
      echocardiography in the general intensive cares is compromised by the acoustic
      window. However, TEE can flyover this difficulty adding to the advantages widely
      described of the transthoracic echocardiography (TTE) other high values 1. The
      TEE manages to do the dynamic evaluation of the necessity of fluids, able to
      discriminate fluid responders, able to distinguish types of shock, assess
      systolic and diastolic function of both ventricles, able to evaluate other
      structures of the heart and be a guide to therapy. The use of the
      echocardiography in the ventilated patient admitted to the general intensive care
      unit still lack for some definition. This clinical commentary was carried out by
      the intention of revising the most relevant literature that values the use and
      efficiency of the TEE in the ventilated critically ill patient in order to
      explain its use and consequently helping to implement the TEE in clinical
      practice. So, one managed to define the application of the TEE in the critically
      ill patient in several clinical scenarios, the haemodynamically unstable patient,
      the patient with global respiratory insufficiency, the patient with hipoxemia.

PMID- 22863481
TI  - Echocardiography by the non-cardiologist: a curriculum for the fast track
      strategy.
AB  - A formal echocardiographic approach in a general intensive care unit requires a
      24 hour availability of an expert in echocardiography, who could not be easily
      found. Therefore, a goal-directed echocardiogram strategy specifically tailored
      to the intensivist should be created. The concept of goal-directed
      echocardiography (GDE) has been incompletely evaluated and it is necessary to
      find a curriculum program to grant proficiency. We propose the Fast-Track
      Echocardiographic Strategy (FTES) program to accomplish both objectives. All
      medical associations of echocardiography agree that extensive training and
      experience are needed to acquire and interpret a formal echocardiogram, however,
      to answer the five questions of FTES a simpler curriculum program would be
      enough. The aim of this review study was to propose a curriculum to teach non
      cardiologist physicians intensivist (NCPI) to use a GDE such as FTES. A search
      for published literature, from 1999 until June 2008, in English and French
      languages in Medline was undertaken in order to find out the most relevant and
      contemporary studies in this area. Strength of evidence of the articles found was
      based on five strengths of evidence. A framework for published medical research's
      critical appraisal and a checklist for sources of bias were used for assessment
      of studies quality. In overall, all studies showed it was possible to teach NCPI
      to use a GDE examination. After a critical appraisal of the literature, we
      proposed FTES program to grant proficiency to NCPI in a GDE, to be used in
      hemodynamic unstable critically ill patients (hypotension with or without
      hypoxemia), to answer five simple questions, in order to define an hemodynamic
      profile and consequently be able to optimize their treatments. In conclusion,
      probably FTES program should at least be considered.

PMID- 22863482
TI  - [Cerebrospinal fluid biomarkers for the early diagnosis of Parkinson's disease].
AB  - In current medical practice, the diagnosis of Parkinson's disease remains
      essentially clinical. This practice determines that the diagnosis of Parkinson's
      disease is done in an already advanced neuropathological stage of the disease.
      The aim of this study is to review the validity of cerebrospinal fluid protein
      biological markers in the early diagnosis of Parkinson's disease. The a-synuclein
      and DJ-1 proteins, due to their role in the hereditary Parkinson's disease, have
      been the most widely studied cerebrospinal biomarkers. Nevertheless, they have
      had divergent results mostly owing to different processing, identification and
      control of laboratory techniques. The new proteomic techniques, directed to the
      detection of multiple undifferentiated proteins in cerebrospinal fluid (eg.
      ceruloplasmin, chromogranin B, apoH), are promising. The early diagnosis of
      Parkinson's disease is imperious as it is a progressive neurodegenerative
      disorder that causes extensive morbidity. Most of current scientific research in
      Parkinson's disease is focused on the discovery of neuroprotective drugs. Thus,
      the definition of biomarkers for the early diagnosis of Parkinson's disease is
      highly relevant.

PMID- 22863483
TI  - [The relevance of body composition in cancer patients: what is the evidence?].
AB  - In the past few years, there has been a growing interest on body composition
      changes of cancer patients. Muscle mass and fat mass are pointed out as the most
      important compartments from a physiological point of view, as their changes are
      the ones with the most impact on disease. The excess of fat mass is related with
      increased risk of incidence and recurrence of some types of cancer, and some
      studies identify it as a major contributing factor for increased morbidity and
      mortality in cancer patients. Weight loss in cancer is frequent and is associated
      with symptoms, circulating pro-cachectic substances produced by the tumour,
      and/or hypermetabolism states, not compensated with adequate intake. Muscle mass
      depletion is the most worrying, and has been associated with decreased functional
      capacity, increased toxicity of anti-neoplastic treatments, longer length of stay
      and higher risk of nosocomial infections. In end stage disease, some patients may
      develop cancer cachexia, an irreversible condition highly associated with
      mortality. Of note that, lean body mass depletion may occur with excess fat mass
      (sarcopenic obesity), a condition that combines the health risks of obesity and
      those of sarcopenia. The high prevalence of malnutrition in cancer patients
      justifies its relevance. Many patients point it as a cause for the reduction of
      physical, cognitive, emotional and social functions, as well as anorexia,
      fatigue, dyspnoea, insomnia, gastrointestinal symptoms and worse Quality of Life.
      Additionally, body composition may be affected by nutrition, lifestyles and
      physical activity; therefore, any approach to the patient should include all
      these dimensions, with special emphasis on individualised nutritional
      intervention. Therefore, nutritional therapy should be adjuvant to any treatment,
      as it is essential in all stages of the disease: for its development, during the
      treatment(s) and in the follow-up period. The aim of nutritional intervention is
      to promote changes in body composition, by maintaining or increasing lean body
      mass and keeping fat mass in healthy levels, which may have a positive impact on
      Quality of Life, response to treatment(s), prognosis and reduced health care
      costs.

PMID- 22863484
TI  - [Demoralization: introducing the concept and its importance for palliative care].
AB  - Demoralization refers to a persistent failure of coping with stress as defined by
      Jerome Frank thirty years ago. Feelings of despair, isolation, hopelessness, loss
      of meaning and existential distress are the core features of the definition of
      demoralization. It is frequently associated with a chronic medical illness, fear
      of loss of dignity and perception of being a burden on others and it evolves to a
      desire to die. The authors reviewed the literature related to this concept and
      present the evidence related to the diagnosis, classification, treatment and
      relation of demoralization with the palliative care setting.

PMID- 22863485
TI  - [Food for health: primary-care prevention and public health--relevance of the
      medical role].
AB  - Each individual is unique, with genetic factors that interact with a particular
      environment. Therefore, the daily energy requirements should be calculated
      individually and have to consider the several factors which influence them: basal
      metabolic rate, diet-induced thermogenesis, physical activity, specific diseases,
      among other factors. Food provides macronutrients: carbohydrates, proteins and
      lipids, as well as micronutrients: vitamins, minerals and oligoelements, which
      should be eaten daily in the recommended amounts during the life cycle, e.g.
      pregnancy, childhood, adolescence, adulthood and aging. Health professionals can
      use the "Roda dos Alimentos Portuguesa" to teach and guide the population on how
      to eat, whether they are healthy or ill individuals, in order to meet their
      nutritional needs. Through this tool it is possible for everyone to understand
      and to practice a diet that is: 1) complete (eating foods from all groups), 2)
      balanced (to respect the proportions of each food group, adjusting the
      recommended portions/amounts for each individual), and 3) diversified (to choose
      different foods within each group). Some studies show that food marketing and
      advertising influence the consumers' choices since childhood. There is already
      some Regulation in this field, especially about nutrition and health claims.
      However, a permanent supervision of food marketing is necessary, to ensure
      compliance with the European Regulation from EFSA. It is crucial to teach and to
      encourage people to carefully read the food labels before purchasing. Health
      professionals should also be aware, academically and professionally, about the
      basics principles of Food and Health Promotion. The unique and essential role of
      the Professionals of Nutrition needs to be valued and recognized, and these
      professionals have to be integrated in sufficient number, in the
      multidisciplinary teams of the National Health Service, whether in Hospitals or
      Health Care Centers for the ambulatory population. These are the interventions
      and attitudes that make a difference and that are actually effective in
      preventing and/or treating many chronic diseases. Hence it is possible to improve
      health and quality of health services provided to the population (public health
      scope) and that of patients (clinical practice scope) as well as to optimize
      costs in health.

PMID- 22863486
TI  - [Abortion: legal, deontological and ethical framework].
AB  - Pregnancy interruption before fetal viability limit is inherent to a
      multidisciplinary reflection, due to the conflicts involved. Portuguese laws have
      been altered along time in the way of women's health protection, allowing the
      needed information and support towards a free, informed and enlightened decision.
      Deontological determinants about health professionals towards abortion indicate
      the practice accordingly the law. Nevertheless, it is safeguarded their right to
      consciousness objection. Ethical discussion about abortion, in its different
      ways, includes the concern about the value of intrauterine human life, and also
      the respect for individual autonomy. Even though the debate about intrauterine
      human life moral status is viewed from different theories and points of view, it
      is concluded that different perspectives about this matter are acceptable, in an
      interpersonal diversity valorization point of view.

PMID- 22863487
TI  - [Sleep disturbances in schizophrenia].
AB  - INTRODUCTION: Schizophrenia is often related with sleep disorders. In clinical
      practice insomnia is a common feature in schizophrenia. Difficulty falling
      asleep, maintaining or achieving a restful sleep is associated with symptoms
      severity and has been listed as a prodromal symptom of psychotic relapse. Sleep
      disturbances in schizophrenia may arise during the acute phase of illness and
      persists in many cases in chronic phase. OBJECTIVES: The authors intend to review
      the main sleep disturbances observed in schizophrenia, the possible
      pathophysiological mechanisms, their clinical impact, and the effects of
      antipsychotic medication on sleep architecture. METHODS: This study was carried
      out a systematic search of published literature from January 1965 to May 2010,
      through PubMed, using the following key words: sleep, REM sleep, NREM sleep,
      schizophrenia, polysomnography, actigraphy and antipsychotics. RESULTS: Most
      changes found in objective studies using the polysomnography, in patients with
      schizophrenia are: reduction of total sleep time, decrease in slow wave sleep,
      REM latency and sleep efficiency. Studies using actigraphy also reveal that these
      patients experience changes in circadian rhythm sleep disorders, specifically the
      irregular type and phase advance. Although some sleep disorders improve with
      antipsychotic treatment, in many cases, even during the remission of the disease,
      sleep continues fragmented , suggesting that there are physiopathologic
      mechanisms involved in sleep disturbance in these patients. CONCLUSION: Privation
      of adequate and restful sleep has a negative impact on rehabilitation strategies,
      quality of life of patients with schizophrenia, and may contribute to worsening
      of cognitive deficits.

PMID- 22863488
TI  - [Depression in palliative care: prevalence and assessment].
AB  - Depression is the most common mental health problem in palliative care, yet it's
      widely misunderstood, underdiagnosed, undertreated and considered a complex
      medical task. Psychological distress is a major cause of suffering among patients
      and families and it's highly correlated with reduced quality of life and
      amplification of pain. Terminally-ill individuals who suffer from depression are
      also at high risk of suicide and desire for a hastened death. Every patient
      receiving palliative care should receive a complete personal and familial
      psychiatric history, with risk factors, as well as the typical signs and symptoms
      in the terminal disease. There are two different approaches to assess depression
      in palliative care: Categorial vs Dimensional The Hospital Anxiety and Depression
      Scale (HADS) is the most used assessment method for depression in advanced
      disease and it's validated to the Portuguese population. HADS overcomes the
      biggest problem when evaluating depression in the terminally-ill: the influence
      of somatic symptoms due to the underlying disease on the results of the
      depression scales. In this article we revise other approaches for the assessment
      of depression in advanced disease: single question vs two-item question;
      structured clinical interview and diagnostic criteria. Clinicians who care for
      terminally-ill patients must develop competences on the psychological area,
      developing state-of-the-art clinical skills that provide quality of life and
      comfort to patients and their families.

PMID- 22863489
TI  - [Family work in geriatric psychiatry].
AB  - Dementia and other late-life conditions in neuropsychiatry impose a heavy burden
      on society as a whole and in families in particular. A number of clinical
      presentations involving family aspects may be seen in clinical practice in a
      range of diagnoses (Alzheimer's disease, other dementias, depression or any other
      psychiatric disorder in the elderly). As a consequence, there is a growing trend
      towards working with families in geriatric psychiatry. Marital issues are not a
      frequent target for specific clinical intervention, but couple therapy may be
      useful regardless of age. The effectiveness of family systems therapy has not
      been widely evaluated in psychogeriatrics, so far. However, it may be a powerful
      resource when family dynamics must be addressed, mostly in families where
      dysfunctional circularities precede the outburst of severe clinical problems.
      More often, family psychoeducation will be the first indication, in different
      formats, settings and levels of intensity. However, context reading and
      systemically-informed work are not restricted to classical family therapy and do
      not imply it. Is has been suggested that family psychoeducation should sometimes
      include a stronger family systems perspective. Structured and feasible family
      assessments should always precede interventions. Indeed, they are a first step of
      the intervention itself, while necessarily reviewed through the course of family
      work. Ageism perhaps still influences to some extent health professionals'
      attitudes, including the ones of family therapists, leading to the
      underutilization of family approaches in the elderly. However, working with
      families remains a core process in geriatric psychiatry and family therapy may be
      a powerful resource in particular cases.

PMID- 22863490
TI  - [Parkinson's disease: a clinical update].
AB  - Parkinson's disease (PD) is a common disorder that causes a marked decrease in
      the quality of life of patients and implies high costs at the social, familiar
      and economic levels. The diagnosis is essentially achieved on clinical grounds
      and there is an extensive list of possible differential diagnoses, thus being
      fundamental to recognize the typical clinical features of PD, and then proceed to
      effective treatment, thus improving disability and the quality of life of
      patients. This review article, built on evidence-based knowledge and clinical
      experience, approaches pathogenesis, clinical features, the diagnostic
      methodology and current concepts in the treatment of PD in a pragmatic and
      updated manner.

PMID- 22863491
TI  - [Alcohol liver disease patients and liver transplantation: a psychosocial
      approach].
AB  - One of the most common indications for Liver transplantation is Alcohol Liver
      Disease (ALD). Transplant recipients with ALD have a similar prognosis in terms
      of medical evolution and quality of life to those with other liver diseases. ALD
      is present when alcoholism (alcohol dependence /abuse) or heavy drinking coexists
      with chronic/acute liver disease. In the present article difficulties in
      establishing this diagnosis are debated. The main predictors of alcohol intake
      relapse after transplantation are: pre-transplantation abstinence (> 6m), social
      support, diagnosis acceptance, history of previous treatments, alcohol abuse VS
      dependence, Vaillant prognosis factors, good adherence (good prognosis); and
      family history of alcoholism, psychiatric history (psychosis, personality
      disorder), duration of alcoholism period, quantity of alcohol /day consumed (bad
      prognosis). Based in these factors we present a new evaluation scale. Diagnosis
      of alcohol relapse depends on the criterion used. Relapse rate is 5.6% /year. In
      the end of this article we discuss the different psychopharmacological and
      psychological methods used to treat pos-transplantation alcoholism relapse and
      some ethical aspects related to discrimination of patients with ALD.

PMID- 22863492
TI  - [Training in forensic psychiatry: comparative issues towards a rethinking of the
      Portuguese model].
AB  - BACKGROUND AND AIMS: Forensic psychiatry has experienced a significant
      development in the last few decades. Several mechanisms underlie this shift,
      including deinstitutionalization of mental health patients and extraordinary
      progress in neurosciences, imaging technologies and psychology, just no name a
      few. This development has put in evidence specific needs for training and
      education. A review and comparison of forensic psychiatry training in several
      European countries, U.S.A. and Brazil is made. METHODS: A mixed approach was
      used, including a) systematic literature review (Pubmed search, 1989-2009) and
      cross-reference search and inclusion; b) specific online sites search (e.g.
      medical associations or scientific societies responsible for forensic psychiatry
      training); c) direct contact with psychiatrists and forensic psychiatrists.
      RESULTS AND CONCLUSIONS: Forensic psychiatry training is still a heterogeneous
      field. While not all countries have specialization, subspecialization or
      competency certification in forensic psychiatry, there has been, however, a
      definite shift towards its individuation as a specific technico-scientific area.
      This contributes to an improvement in quality standards and promotes research.
      Notwithstanding, forensic training in general adult and child psychiatry's
      residencies should continue to be strengthened as it is likely that most forensic
      activities will remain at their care in the near future.

PMID- 22863493
TI  - [BRAF gene mutation in the natural history of papillary thyroid carcinoma:
      diagnostic and prognostic implications].
AB  - The papillary carcinoma is the most prevalent malignant neoplasm of the thyroid
      gland, representing 85-90% of all cases, and its incidence has been increasing in
      recent years. It is relatively indolent, however other types poorly
      differentiated or anaplastic, are more aggressive and usually associated with
      poor prognosis. Approximately half of these papillary carcinomas harbor a thymine
      to-adenine transversion (T1799A) point mutation, in the gene encoding the
      serine/threonine-kinase B-type Raf kinase (BRAF), with substitution of valine by
      glutamate (V600E). Mutated BRAF, generates a constitutive activation of the
      mitogen-activated protein kinases (MAPK) signaling pathway, which plays a
      critical role in transmitting proliferative signals generated by cell surface
      receptors and cytoplasmic signaling elements, to the nucleus. BRAF mutation is
      mutually exclusive with other common genetic alterations, supporting its
      independent oncogenic role in cell proliferation, survival and tumor de
      differentiation. The BRAFV600E occurs exclusively in papillary thyroid carcinoma
      and papillary carcinoma-derived anaplastic cancer, rising as a specific
      diagnostic marker for this tumor when identified in cytological / histological
      exams. This mutation has recently emerged, as a potential prognostic marker for
      papillary thyroid carcinoma, after several studies have found this mutation to be
      associated with some clinicopathological characteristics, known to predict tumor
      recurrence and progression, including, for instance, old patient age,
      extrathyroidal invasion and lymph node metastasis. It is therefore considered a
      marker of aggressive disease in these tumors, associated with increased cancer
      recurrence and even loss of radioiodine avidity. Several studies were not able to
      confirm these associations. It has become clearer that BRAF mutation will likely
      have significant impact on the clinical management of papillary thyroid
      carcinoma.

PMID- 22863494
TI  - [Anemia in Chronic Kidney Disease: from facts to clinical practice].
AB  - Anemia in Chronic Kidney Disease (CKD) is present in approximately 90% of
      patients with glomerular filtration rate below 25-30 mL/min. It's impact in the
      quality of life makes it one of the major problems in CKD patients. Although the
      etiology is multifactorial the suboptimal production of erithropoietin caused by
      renal mass loss appears to be of major importance. After the introduction of
      Erythropoiesis Stimulating Agents (ESA's) the treatment of anemia in CKD has
      changed dramatically. Today, ESA's have a fundamental role in the increase of Hb
      values in CKD. Previously, severe anemia was frequent and blood transfusions were
      often necessary to improve patients quality of life. Small observational studies
      performed during the late 80's suggested that high Hb values may be benefic in
      CKD patients. At that time, the use of ESA's became universal. Later randomized
      trials tried to show the positive impact of rising Hb levels with ESA's in
      patient's outcome. The results of such studies were disappointing. Some of them
      even documented higher mortality associated with near normal Hb levels, failing
      to prove the real benefit of the complete correction of CKD anemia. We're still
      waiting for new randomized trials to be elucidated about the optimal target of Hb
      to achieve in CKD and the treatment algorithm with ESA's. Current evidence
      suggests that Hb values must be targetted at 11-12 g/dL, without reaching the
      complete correction of anaemia.

PMID- 22863495
TI  - [Low-level laser therapy in the treatment of diabetic ulcers: an evidence
      problem].
AB  - INTRODUCTION: Diabetes Mellitus is the leading cause of lower limb amputation,
      representing a significant economic cost for health services. The development of
      diabetic ulcers is a main risk factor for amputations, which have a high
      mortality rate at five years. The ischemia caused by macrovascular disease is a
      key pathophysiological factor in the development of ischemic ulcers. Existing
      treatments are prolonged and associated with high rates of failure and relapse,
      requiring the combination of multiple therapeutic modalities. Lowlevel laser
      therapy has been used as an adjuvant therapy for diabetic foot ulcers, since the
      1960's, due to its hypothetical stimulating effects over microcirculation and
      tissue repair. MATERIAL AND METHODS: Identification of published scientific
      studies through a literature search on PubMed, The Cochrane Library and Cochrane
      Controlled Trials Register. DISCUSSION AND CONCLUSIONS: Existing evidence is
      favourable for in vitro cell models, but conflicting in animal models and human
      populations. There is significant methodological heterogeneity, which may be
      responsible for discordant results. Guidelines are proposed for future studies in
      this area, including the detailed characterization of ulcers and the parameters
      of laser treatment. Well-controlled studies, randomized and double-blind are
      needed. Accordingly to the primum non nocere, laser therapy can and should be
      used as adjunctive therapy in the treatment of diabetic foot, because it isn't
      invasive, has low costs and is a fast therapy without significant adverse
      effects.

PMID- 22863496
TI  - [Fertility preservation in women with oncologic disease].
AB  - Every patient with a cancer diagnosis should be informed about the impact the
      disease and its treatment have in her future fertility. Several strategies have
      been implemented with the purpose to overcome the issue of follicular depletion
      associated with the chemotherapic agents. When possible, cryopreservation of
      embryos, either isolated or associated to other procedures, is the technique that
      presents more scientific evidence and the best pregnancy rates. Other procedures,
      more experimental, could be proposed in the setting of clinical studies and
      allways after informed consent. This is the case of cryopreservation of ovaric
      tissue, the use of GnRH agonists and the cryopreservation of oocytes. Finally
      some emerging techniques like in vitro maturation of oocytes, anti-apoptotic
      drugs that protect the gonadals from the toxicity of chemotherapy or the use of
      stem cells to improve the ovarian reserve, can in the future have a place in
      oncofertility preservation. In patients with breast cancer the technique that
      shows better outcomes continues to be the cryopreservation of embryos after a
      protocol of follicular stimulation allied to the aromatase inhibitors with lower
      levels of plasmatic stradiol. Children are a special group in which the options
      are limited, being the cryopreservation of ovaric tissue the most promising
      strategy although still constitutes an experimental technique. Further randomized
      clinical trials are necessary with the aim of assessing the efficacy and security
      profile at long term of these procedures.

PMID- 22863497
TI  - [Breastfeeding: the importance of intervening].
AB  - BACKGROUND: Breast milk is considered by the WHO the ideal food for the first
      months of life. Although health professionals are aware of recommendations, high
      rates of drop-outs have been identified in Portugal. A false notion of
      hypogalactia is the major factor for early termination, which is allied to the
      technical difficulties of the feeding. Health professionals, often lacking
      training in the area, may have difficulty in reassuring mothers in these
      situations. In Portugal, at the 3rd month, most mothers stop breastfeeding by
      indication of their medical assistant. OBJECTIVES: Gather evidence about the
      advantages of breast-feeding compared to artificial milk, and establish useful
      strategies in clinical practice to avoid early withdrawal. METHODS: A survey was
      conducted for articles from the last six years in the major sites of evidence
      based medicine and reference sites (Pubmed, Cochrane, National Guideline
      Clearinghouse, Tripdatabase, WHO). RESULTS: Breast-feeding is clearly associated
      with benefits to the infant, including significant protective effects for
      gastrointestinal infections (64%), middle ear (23- 50%), severe respiratory
      infections (73%) and for acute lymphocytic leukemia (19%) and sudden death
      syndrome in infants (36%). We also found long-term benefits, such as for obesity
      (7-24%) and other cardiovascular risk factors in adulthood. The mother also
      benefits from its protective effect for cancers of the breast and ovary, and
      diabetes mellitus type 2 as also, proportionate to the duration of breastfeeding.
      Health professionals have an important role in the initiation and continuation of
      breastfeeding. The notion of its advantages, the communication prior to delivery,
      accessibility support and training in technical aspects of correct picks are the
      proven strategies for evidence explored in the article. DISCUSSION: Breast milk
      contains several unique and exclusive elements, orchestrators of its health
      benefits. Postnatal period is critical to the development of neuro--hypothalamic
      circuits involved in appetite control--nutritional programming--in which leptin,
      present in breast milk, appears to have a decisive role. CONCLUSION: Despite
      scientific advances, breast milk continues to demonstrate clear advantages for
      human health in the short and long term. Proper feeding technique is not often
      achieved by the dyad mother-infant alone, warning for a greater involvement of
      health professionals. It is urgent to continue to insist on training for the
      improvement of the indices relating to this area in Portugal.

PMID- 22863498
TI  - [Transfusion-transmitted protozoal infections: what is the risk in non-endemic
      countries?].
AB  - Protozoal infections that are efficiently transmitted by blood transfusion
      include Malaria, Chagas Disease, African Trypanosomiasis, Leshmaniasis,
      Toxoplasmosis and Babesiosis. With exception of Toxoplasmosis and Leishmaniasis,
      these diseases are endemic in mainly tropical low income countries and, in non
      endemic countries like Portugal, the reported cases are imported from these
      endemic areas by travelers or immigrants. Globalization, with increasing travel
      and immigration poses the risk of exposition to these infectious agents and
      raises the issue of possible transmission by blood transfusion. According to
      recommendations of the Council of Europe, strategies to prevent the transmission
      of these infections by blood transfusion have been implemented. Given that the
      risk is introduced by a specific group of donors, travelers or immigrants from
      endemic areas, the main strategy to prevent this transmission depends on the
      identification of these groups of donors using questionnaires during the pre
      donation procedures. Additional measures, like serological testing and pathogen
      inactivation procedures, when available, contribute not only to reduce the risk
      of transmission but also to avoid unnecessary rejections.

PMID- 22863499
TI  - [Peripheral facial paralysis: the role of physical medicine and rehabilitation].
AB  - Peripheral facial paralysis (PFP) is a consequence of the peripheral neuronal
      lesion of the facial nerve (FN). It can be either primary (Bell's Palsy) or
      secondary. The classical clinical presentation typically involves both stages of
      the hemiface. However, there may be other symptoms (ex. xerophthalmia,
      hyperacusis, phonation and deglutition changes) that one should recall. Clinical
      evaluation includes rigorous muscle tonus and sensibility search in the FN
      territory. Some useful instruments allow better objectivity in the patients'
      evaluation (House-Brackmann System, Facial Grading System, Functional
      Evaluation). There are clear referral criteria to Physical Medicine and
      Rehabilitation. Treatment of Bell's Palsy may include pharmacotherapy,
      neuromuscular training (NMT), physical methods and surgery. In the NMT field the
      several treatment techniques are systematized. Therapeutic strategies should be
      problem-oriented and adjusted to the patient's symptoms and signs. Physical
      methods are reviewed. In about 15-20 % of patients permanent sequelae subside
      after 3 months of evolution. PFP is commonly a multidisciplinary condition.
      Therefore, it is important to review strategies that Physical Medicine and
      Rehabilitation may offer.

PMID- 22863500
TI  - [Drug induced movement disorders: role of antipsychotic drugs].
AB  - This article reviews the current knowledge on drug-induced movement disorders
      (DIMD) epidemiology, pathophysiology, phenomenology and treatment. This review is
      justified by its high prevalence in certain medical specialties, the need to
      include them on movement disorders etiologic differential diagnosis and the
      potential economical burden. The acronym DIMD refers to a heterogeneous group of
      neurological syndromes, the most prevalent being parkinsonism, dystonia,
      dyskinesia and akathisia. Soon after neuroleptics (D2 dopamine receptor blocking
      agents) introduction in clinical practice, the first acute dystonic reactions
      were reported. Later, was recognized that extrapyramidal symptoms could occur in
      association with their chronic use. Nowadays, several non dopamine receptor
      blocking drugs and drugs of abuse are recognized as potential inductors of
      extrapyramidal reactions.

PMID- 22863501
TI  - [The role of major histocompatibility complex in the progression of HIV
      infection].
AB  - INTRODUCTION: Despite being uncommon, there is a small group of HIV infected
      that, even without treatment, do not evolve to AIDS. Several theories have been
      proposed over time trying to explain this phenomenon. This article addresses the
      role of HLA in the TC modulation. OBJECTIVES: Review the literature about the
      role of MHC in the progression of HIV infection and identify which HLA has a
      greater role in the progression of HIV infection. METHODS: There were included 24
      original articles (19 per bibliographic search, four for cross reference and one
      by a survey of recently published articles) Development - Unlike humans,
      chimpanzees can prevent the progression of HIV disease. Their HLA has also a
      greater similarity with the HLA of LTNP. These phenotypes of progression of
      infection are the result of a combination of protective and progressive factors.
      Among the protective factors are HLA class I molecules, especially HLA-B. Several
      studies have been published on this subject and showed that the main HLA not
      involved in the progression of the HIV infection are HLA B27 and B57. A study
      recently published was able to show that variations in specific amino acids have
      been associated with the management of HIV infection. CONCLUSION: It is now
      thought that the major genetic factor capable of modulating the progression of
      HIV infection is the HLA-peptide interaction and more research is needed so that
      knowledge can be used to support the treatment of patients infected with HIV
      infection.

PMID- 22863502
TI  - [Macroprolactinemia--laboratory determination and its clinical significance].
AB  - Since prolactin (PRL) (a hormone produced by the anterior pituitary) was first
      identificated, the existence of hyperprolactinemic syndrome has been recognized.
      Main symptoms are galactorrhea, oligomenorrhea, amenorrhea and infertility in
      women and decreased libido and impotence in men. Macroprolactinemia reflects the
      predominance of circulating forms with reduced bioactivity not associated with
      typical clinical manifestations of hyperprolactinemia. It is identified by
      immunoassays commonly used in clinical practice, resulting in hyperprolactinemia.
      Polyetilenoglycol (PEG) is the most used method that removes PRL from serum. It
      is likely that the phenomenon of macroprolactinemia is consistently
      underestimated and unrecognized. Manufacturers of immunoassays for PRL have been
      slow to incorporate in the literature, validated protocols, and data related to
      the interference of PEG. From a clinical and biochemical point of view and, the
      main concern should be to avoid unnecessary investigation and treatment.

PMID- 22863503
TI  - [The dentist's role in the child abuse: diagnosis and report].
AB  - Child Abuse is a frequent problem worldwide that surpasses ethnicity, religion,
      culture, economic and social classes. In the United States of America child
      protective services account, per year, over one million cases of child abuse or
      neglect. In Portugal, the incidence of the problem is unknown but each year
      thousands of abused children are accompanied by the Commissions for the
      Protection of Children and Youth at Risk. This abuse threatens children's
      physical, emotional and intellectual development, as well as their dignity,
      security, well-being and even their own lives. The body regions most frequently
      affected in physical abuse, are the cranium, neck and orofacial region, in fact,
      about 50% of the injuries arising from child abuse occur in the orofacial region.
      These data place the dentist in a privileged position to make the detection,
      diagnosis and report of child abuse. Therefore, these professionals must be
      prepared to recognize, diagnose and report their suspicions to the appropriate
      authorities, which play a key role in victims protection and criminal
      investigation. This review intends to stress the important role of the dentist in
      the detection, diagnosis and report of child abuse, systematizing child abuse
      risk factors and indicators essential to the intervention of these professionals.
      This problem's approach is multidisciplinary, involving particularly dentists,
      who must obtain continuing education and training in this area.

PMID- 22863504
TI  - [Eosinophilic esophagitis].
AB  - Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus
      characterized by significant and isolated infiltration of the esophageal mucosa
      by eosinophils, associated with clinical symptoms of esophageal dysfunction,
      affecting children and adults. It is an increasingly frequent cause of symptoms
      similar to gastroesophageal reflux disease but refractory to anti-acid
      therapeutic. It is commonly associated with food allergies or other atopic
      diseases. Since there are no symptoms, signs, serological biomarkers or
      endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of
      suspicion; moreover, due to its chronic relapsing nature the potential to cause
      major esophageal structural changes, its early recognition and close cooperation
      between gastroenterologists and immunoallergologists is essential for the timely
      institution of appropriate therapy. The treatment is based on two main
      strategies: diet and / or pharmacotherapy, depending on the co-existence of
      sensitization to food allergens. It is our aim to review this issue, considering
      recent guidelines, as well as propose a diagnostic and therapeutic algorithm.

PMID- 22863505
TI  - [Use of valerian in anxiety and sleep disorders: what is the best evidence?].
AB  - BACKGROUND: Anxiety disorders and sleep problems are common in the general
      population and are a cause of frequent consultations in primary care. These
      problems have significant impact on quality of life and functionality of
      individuals. The extracts of valerian root have been widely used for a long time
      by the population and physicians, for their sedative effects, hypnotic and
      anxiolytic. It is therefore urgent to know what are the benefits and the risks of
      using this substance for the treatment of anxiety and sleep disorders. OBJECTIVE:
      To investigate the efficacy and safety of valerian for the treatment of anxiety
      and sleep disorders. METHODS: A research was carried out for clinical practice
      guidelines, systematic reviews (SR), meta-analysis (MA) and randomized controlled
      trials (RCT) in Pubmed, sites of evidence-based medicine and Index das Revistas
      Medicas Portuguesas using the MeSH terms valerian, anxiety and sleep disorders,
      and respective DeCS, analyzing articles in English, Spanish, French or
      Portuguese, published between January 2000 and March 31, 2010. We also reviewed
      references of relevant articles. We used the Strength of Recommendation Taxonomy
      (SORT) from American Family Physician to evaluate the level of evidence and
      assigning the strength of a recommendation. RESULTS: We found 173 articles of
      which four were selected which met the inclusion criteria: a meta-analysis, a SR
      and a RCT concerning the use of valerian in sleep disorders, and an SR on the use
      of valerian in anxiety disorders. The evidence is insufficient regarding the
      efficacy of valerian in the treatment of anxiety disorders (SOR A). There seems
      to be some evidence of the effectiveness of valerian for treating insomnia, which
      is limited by the quality of existing studies (SOR B). Valerian root is well
      tolerated and safe, with infrequent and benign side effects (SOR A). DISCUSSION:
      The evidence is currently insufficient to recommend the use of valerian for the
      treatment of anxiety disorders. The evidence in insomnia is limited by the
      contradictory results of studies reviewed and their methodological problems,
      although it seems to have some effect in mild to moderate insomnia. Despite that,
      valerian is a safe substance. More RCT are needed, with samples of adequate size,
      with standardization of measures to assess quality of sleep and levels of anxiety
      and standardization of dose, type of preparation of valerian used and the time
      for its use.

PMID- 22863506
TI  - [The chemokines and their receptors: characteristics and physiological
      functions].
AB  - Chemokines are members of a large family of small soluble proteins, which were
      discovered by their adhesion control, chemotaxis and leukocyte activation
      abilities. Nevertheless, it is now known they are involved in other equally
      important functions, namely, angiogenesis, haematopoiesis, embryologic
      development, B and T cell development, dendritic cell maturation, inflammation,
      infection, tumour growth and metastasis. Hence, the increasing interest on
      chemokines and their receptors is due not only to chemokine chemoattractant
      properties but also to their contribution to immune processes that do not
      directly involve leukocyte migration. According to the number and spacing of the
      first two conserved cysteine residues in the N-terminal, chemokines have been
      divided into four subfamilies (CXC, CC, CX3C and C) and mediate their functions
      by binding to G-protein coupled receptors. This interaction may result in
      multiple signal transduction pathways, depending on the player subunit and the
      effector protein activated. It triggers a cascade of intracellular events that
      promote from gene transcription to cytoskeleton rearrangement and chemotaxis. The
      pattern of migration of cell populations and of leukocytes in particular is
      closely related to chemokine receptors expression. One of the characteristics
      associated with the chemokine system is an apparent redundancy: several chemokine
      receptors bind multiple ligands and in turn, a single ligand binds multiple
      receptors. Another overall classification of chemokines is based on functional
      criteria that group them into homeostatic and inflammatory chemokines.
      Homeostatic chemokines are constitutively expressed and regulate the migration of
      leukocytes and their precursors. The inflammatory chemokines are inducible and
      regulate the leukocyte migration into tissues in response to an inflammatory
      stimulus, such as tissue damage, inflammation or infection. Many of the
      inflammatory chemokines have wide target-cell selectivity, acting both on the
      cells of the innate and adaptive immunity. The purpose of this review is to
      collect all the research that has been done so far concerning chemokines and
      their receptors through analysing their expression patterns, in order to define
      their cellular localisation with the aim of understanding their role in human
      physiology.

PMID- 22863507
TI  - [Drug--induced splenomegaly].
AB  - The diagnosis of splenomegaly due to drugs is based on a recent history of
      exposure to a drug before the spleen enlargement. The purpose of this paper is to
      review studies of the literature on drugs that may induce to splenomegaly. Drugs
      may provoke the enlargement of spleen by direct effect in splenic cells or as a
      side effect of disturbances in other organs, mainly liver and haematoimmunologic
      system. Some drugs provoke severe haemolysis associated with splenomegaly.
      Another cause of spleen increasing in size is the venous congestion due to liver
      disturbance with portal vein occlusion. All these drug side effects are usually
      transitory and splenomegaly disappears when the medication is discontinued. This
      is a complex problem that must be better studied to be understood in order to
      prevent its occurrence and to find the best treatment.

PMID- 22863508
TI  - [Aging: a reflection about physical activity and oxidative stress in women].
AB  - The aging process is a universal, multi-factorial and unavoidable process.
      Physical activity is considered an important factor in the prevention of diseases
      caused by aging. The authors propose a review on the theme, evaluating the
      beneficial effects of physical activity and the risks of oxidative stress in
      menopausal women. Nowadays, is known that regular physical activity associated to
      antioxidant supplement is one of the most effective strategies to prevent
      cardiovascular disease, neoplasia, and chronic illnesses specific to old age. The
      authors concluded: the greatest benefits associated with physical activity are
      attained through moderation, since excessive exercise can bring about oxidative
      stress and diseases related to the latter, including death.

PMID- 22863509
TI  - [Myocardial viability assessment].
AB  - The prognosis for patients with chronic coronary artery disease and severe left
      ventricular dysfunction is poor, despite advances in different therapies. The
      assessment of myocardial viability has become an important aspect of the
      diagnosis, prognosis and management of patients with ischemic cardiomyopathy.
      Patients with left ventricular dysfunction, with a substantial amount of severely
      ischemic myocardium are at highest risk, and are likely to benefit from coronary
      revascularization. Patients with predominantly scar tissue should be treated
      medically. Multiple imaging techniques have been developed to assess viable and
      nonviable myocardium by evaluating perfusion, cell membrane integrity, glucose
      metabolism, fibrosis and contractile reserve. PET FDG-F18, myocardial perfusion
      scintigraphy (with (201)Tl and (99m)Tc), dobutamine stress echocardiography and
      more recently magnetic resonance have been extensively evaluated for assessment
      of viability and prediction of clinical outcome after coronary revascularization.
      In general, nuclear imaging techniques have a higher sensitivity for the
      detection of viability, whereas techniques evaluating contractile reserve have
      higher specificity (with lower sensitivity). Magnetic resonance has a high
      diagnostic accuracy for assessment of the transmural extent of myocardial scar
      tissue. The aim of this article is to review the role of Nuclear Medicine in
      assessing myocardial viability and risk stratification in patients with advanced
      left ventricular dysfunction, and to compare it with other imaging modalities.

PMID- 22863510
TI  - [Stevens-Johnson syndrome and toxic epidermal necrolysis].
AB  - Stevens-Johnson syndrome and toxic epidermal necrolysis are potentially life
      threatening adverse cutaneous drug reactions. Clinically, it manifests as a rash,
      often morbilliform, or atypical target lesions that evolve to epidermal
      detachment. There is mucosal involvement in almost all patients. The loss of
      skin's barrier function has important implications in the maintaining of
      homeostasis in these patients, often determining its internment in Burn Units or
      Intensive Care Units. The drugs most often involved are allopurinol, antibiotics,
      including beta-lactams and sulfonamides, anti-inflammatory drugs (NSAIDs) and
      aromatic anticonvulsants. The clinical manifestations appear on average 7 to 21
      days after the onset of the involved drug. The diagnosis is clinical and
      supported by histopathology, whose main finding is keratinocytes' necrosis and
      cleavage of the dermo-epidermal junction. The differential diagnosis is carried
      out with erythema multiforme, acute generalized exanthematous pustulosis,
      staphylococcal scalded skin syndrome, paraneoplastic pemphigus and graft versus
      host disease. A timely recognition of these situations is of utmost importance in
      order to intervene as early as possible. The suspension of the drug believed to
      be involved is paramount.

PMID- 22863511
TI  - [Cytomegalovirus: is there a place for screening during pregnancy?].
AB  - The maternal and fetal/congenital infection by cytomegalovirus (CMV) during
      pregnancy is the leading infectious cause of neurologic impairment and hearing
      loss. CMV screening during pregnancy has been widely discussed for several years,
      but still no consensus has been established. Most developed countries do not
      recommend it because the majority of infected fetuses will be free of any
      symptom, and there is currently no reliable knowledge about fetal and neonatal
      prognosis and also due to lack of valid, effective and safe treatment during
      fetal life. The aims of this review are to discuss the physiopathology of
      maternal and fetal infection by CMV, the diagnosis and possible treatments, as
      well as to determine the usefulness of a systematic screening during pregnancy.

PMID- 22863512
TI  - [Neuregulin1/ErbB system: importance in the control of cardiovascular function].
AB  - The family of Neuregulins (NRG), growth factors like epidermal growth factor, is
      known to induce growth and differentiation of epithelial, glial, neuronal, and
      skeletal muscle cells. This family comprises four members, being NRG1 the most
      largely studied, particularly at the cardiovascular level. The biological effects
      of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In
      the adult heart, NRG1 is expressed by cells of the endocardial endothelium and
      the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are
      expressed by ventricular cardiomyocytes and are located in T-tubule system and
      intercalated disks in close proximity to the system components of excitation
      contraction coupling. The importance of the NRG/ErbB signaling axis at the
      cardiovascular level became evident after discovering that patients treated with
      trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast
      cancer) can develop ventricular dysfunction and have higher risk of
      cardiomyopathy when co-administered with anthracyclines. Subsequent studies in
      vitro and in vivo have clarified the effects and the respective signaling
      pathways associated with the NRG/ErbB system in the adult heart. Some
      cardiovascular functions of the NRG1/ErbB system have been described at the
      vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium
      level (negative inotropic effect) as well as effect on the survival, cell growth
      and organization of the cardiomyocytes (myofibrillar organization and cell-to
      cell contact between cardiomyocytes). Furthermore, the interaction of this system
      with other neurohumoral mediators has been studied. Thus, there seems to be a
      physiological role in modulating the sympathovagal balance and an interaction
      with endothelin-1 signaling. All these effects result from the activation of
      different intracellular signaling cascades, as a consequence of the binding of
      NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now
      include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt,
      focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial
      growth factor and NO production by endothelial nitric oxide synthase. Thus, the
      aim of this paper was to make an up-to-date review of existing information on
      NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects.

PMID- 22863513
TI  - [Nutritional deficiencies after bariatric surgery: why they happen?].
AB  - Nutritional deficiencies following bariatric surgery are commonly reported in
      scientific literature on surgery and nutrition. It has been estimated that
      approximately 400,000 large obeses underwent bariatric surgery in 2010. The
      surgery technique and consequent altered gastrointestinal function done will
      particularly imply in variations on those deficiencies and health complications.
      A systematic review of several database was done from 1978 until 2010, using as
      keywords protein and micronutrients deficiencies, related to bariatric surgery.
      The better understand of these studies can provide an important improvement on
      this obese therapy, assuring a successful and health weight loss maintenance for
      long term. Therefore, this review provides a significant contribution about this
      topic, pointing several ways on the nutritional intervention and management of
      those patients.

PMID- 22863514
TI  - [Prolactin and the laboratory].
AB  - Up to 95% of adult serum prolactin is monomeric prolactin with a molecular weight
      of 23 kDa. Macroprolactin is a prolactin-antibody complex of molecular weight
      greater than 100 kDa and constitutes less than 1% of circulating prolactin. In
      some cases, hyperprolactinemia is the result of elevated macroprolactin levels,
      misleading the medical approach to the patient. This may involve inappropriate
      and unnecessary imaging investigations and treatment, either medical or surgical.
      The screening of macroprolactin in all the hyperprolactinemic patients could be
      useful and necessary. Presently is facilitated by a simple and rapid laboratory
      test such as the polyethyleneglycol precipitation. Besides the macroprolactin,
      the hook effect is another laboratorial pitfall in the diagnosis of the
      hyperprolactinemia. It is characterized by the finding of falsely low levels of
      serum prolactin in patients with very high prolactin levels and big
      prolactinomas. The hook effect should be excluded in patients with prolactin
      levels less than 200 ng/mL and macroadenomas. It is identified by re-measuring
      the prolactin level after performing a serum dilution. In this article, we focus
      these two pitfalls in the laboratorial diagnosis of the hyperprolactinemia,
      remembering that they could occur and interfere with a correct approach of the
      patient.

PMID- 22863515
TI  - [Diversification in the first year of food life].
AB  - INTRODUCTION: Diversifying food during the first year of life is an extremely
      important step for the adequate nutritional status of infants and their physical
      and psychological development, functioning as a means of transition from
      lactation to feed the family. Despite the introduction of food diversification is
      a necessary step for human development, some issues still exist today, not only
      for the initiation but also in relation to the proper sequence for the various
      types of food, causing different perspectives and ways of acting on part of
      clinicians. OBJECTIVES: To determine the best time for the start of food
      diversification and the best time to introduce certain foods. METHODS:
      Bibliographic search of the literature in English and Portuguese, from January
      2004 to May 2010 through Medline / Pubmed sites and Evidence Based Medicine.
      Twenty-five of fifty-eight articles were selected, given the full availability of
      publications and relevance to the topic. RESULTS: The food diversification should
      never start before 17 or after 2 6 weeks. There is no current evidence that
      delaying the introduction of any antigen after six months reduces the risk of
      food allergy, asthma, allergic rhinitis and eczema, even if there is family
      history of allergy. It is prudent to avoid the introduction of both prior (less
      than four months) and late (more than seven months) of gluten and a gradual
      introduction will reduce the risk of celiac disease, type 1 diabetes and allergy
      to it. The introduction of fish at one year of age reduces the risk of allergic
      diseases at age four at the immunological benefits of its early introduction
      outweigh the risks of sensitization to its antigens. CONCLUSIONS: It is important
      that the onset of food diversification and the introduction of antigens is
      performed within a specified time interval. It is crucial to implement a healthy
      diet for the whole family, to the extent that children learn by example.

PMID- 22863516
TI  - [What is the relevance of nutrition in oncology?].
AB  - Cancer has an increasingly significant impact on society, being a highly
      destabilizing factor in the life of any patient. The disease as well as anti
      neoplastic treatments can profoundly alter biological functions and, remarkably,
      the patients' nutritional status. Thus, Nutrition is a key factor in oncology, by
      influencing the development of the disease, cancer related symptoms, the response
      to, and recovery from treatment(s), and therefore determining the patients'
      Quality of Life and probably prognosis. Therefore, the assessment of Quality of
      Life in any clinical study is essential because it values physical, psychological
      and social factors, which often depend on or are related with Nutrition. The aim
      of this review work, was to explore extent to which individualized nutrition
      intervention improves nutritional parameters (nutritional status and intake),
      Quality of Life, and ultimately the prognosis of the disease. Based on clinical
      research studies conducted until now, early nutritional intervention via
      individualized nutritional counseling, does significantly improve nutritional
      parameters and Quality of Life. It was also found that appropriate and
      individualized nutritional intervention, improves symptoms, reduces morbidity and
      may have the potential to improve the prognosis of the disease. According to the
      reviewed data and guidelines, nutritional therapy should be central and adjuvant
      to any treatment, and should be included in the multidisciplinary approach
      mandatory in oncology. This will allow for more adequate and efficient results
      these patients. Multidisciplinary follow-up, with early nutritional intervention,
      is of major importance in oncology, thus being a key factor for successful
      treatment and recovery of these patients.

PMID- 22863517
TI  - [Surgical basic skills: surgical sutures].
AB  - Given the importance of surgery within the specialty of Obstetrics and Gynecology
      it is crucial to understand the process of wound healing and the suture available
      to surgical repair. The selection of the type of suture depends on the tissue and
      anatomical location. The approximation of wound edges can be made with natural or
      synthetic suture, mono or multifilament. Three properties of a suture material
      affect its handling: memory, elasticity and knot strength. Tensile strength,
      tissue reaction and capability to be absorbed are other important characteristics
      of the suture material.

PMID- 22863518
TI  - [Clinical predictive factors for Crohn's disease complications].
AB  - Crohn's disease (CD) is a progressive disease that is subdivided in three
      phenotypes: inflammatory, stricturing, and penetrating. At diagnosis most CD
      patients have inflammatory disease. However, the natural history of CD evolves
      over time to structural digestive tract complications (strictures and fistulae)
      which are associated with hospitalisations and surgeries. Nowadays, there is
      evidence that early treatment with immunosuppressants and biologics can interrupt
      the development of inflammation- destruction/fibrosis through its potential to
      induce complete mucosal healing. The change in CD natural history, mediated by
      mucosal healing, is associated with a reduction in serious complications
      (hospitalisations and surgeries). Nevertheless, the clinical course of CD varies
      considerably between patients and there is still no definition for the timing of
      immunosuppressants and/or biologics use. This medication is associated to certain
      risks (lymphomas and opportunistic infections) and the difficulty to predict, on
      an individual basis, the progression to complications have triggered efforts to
      identify risk factors that allow at diagnosis to classify patients in high and
      low risk groups and to tailor therapy. This paper is an updated compilation of
      evidence of clinical risk factors predictive for CD complications.

PMID- 22863519
TI  - [Vaccines and pregnancy].
AB  - Routine vaccination is part of the pediatrics universe. In adulthood and
      particularly when women voluntarily access to medical care, immunization should
      be reviewed and updated. There are many doubts that generate in all health
      professionals anxiety and concern about the vaccination of a pregnant woman. This
      article aims to describe the immunological changes in pregnant women, to clarify
      the purpose of immunization during pregnancy, and to enumerate indications,
      contraindications and risks of vaccines of the Portuguese National Vaccine Plane
      and other vaccines against diseases with prevalence in other countries. Due to
      the medical and social impact of vaccination against seasonal influenza and
      influenza A (H1N1) in the winter of 2009, during an influenza (H1N1) pandemic
      flu, we make reference to the indications and vaccination against these
      infections in pregnancy.

PMID- 22863520
TI  - Pierre Youinou: when intuition and determination meet autoimmunity.

PMID- 22863521
TI  - Towards a roadmap in brain protection and recovery.
AB  - This article briefly reviews some of the mechanisms involved in the pathogenesis
      of neurological diseases, i.e. damage mechanisms (DM), and their interactions and
      overlap with protection and reparatory processes (i.e. endogenous defence
      activities). A relationship between DM and endogenous defence activity (EDA)
      regarding therapy principles will also be described. Currently, it is difficult
      to find the correct therapeutic approach for brain protection and recovery,
      especially because we do not fully understand all of the endogenous
      neurobiological processes, the complete nature of the pathophysiological
      mechanisms and the links between these two categories. Moreover, we continue to
      use a simplistic and reductionist approach in this respect. Endogenous
      neurobiological processes, such as neurotrophicity, neuroprotection,
      neuroplasticity and neurogenesis, are central to protection and recovery and
      represent the background of EDA. The biological reality of the nervous system is
      far more complex. In fact, there is an endogenous holistic process of
      neuroprotection and neurorecovery that should be approached therapeutically in an
      integrated way. The current tendency to exclusively frame drug activity in terms
      of single mechanisms and single focus effect might distract from other paradigms
      with greater explanatory power and hinder the development of more effective
      treatment strategies. A change of concept is required in pharmacological brain
      protection and recovery. Prospective considerations include an integrated
      pharmacological approach, focusing on drugs with multimodal activity and
      pleiotropic neuroprotective effect which are biological drugs, rather than single
      mechanism drugs, which usually are chemical drugs.

PMID- 22863522
TI  - Screening outcomes from patients with suspected multidrug-resistant tuberculosis:
      lessons learned in the Philippines.
AB  - SETTING: The high prevalence of multidrug-resistant tuberculosis (MDR-TB) in the
      Philippines is a challenge for the National TB Programme. OBJECTIVE: To assess
      patterns of drug resistance and screening outcomes among MDR-TB suspects
      evaluated from 2003 to 2008 at DOTS-Plus clinics  in the Philippines. METHODS:
      Descriptive study of 4897 consecutive patients with suspected MDR-TB. RESULTS:
      The median time from the first visit until a diagnosis of drug-resistant TB was
      132 days (IQR 110-166 days). Among patients screened for MDR-TB, the most
      frequent resistance  pattern among those previously treated in DOTS facilities
      was resistance to isoniazid (INH) and rifampicin (RMP). Resistance to INH+RMP
      plus fluoroquinolones was the most common pattern among those who had failed
      Category II treatment and patients treated by non-DOTS facilities. Among patients
      with MDR-TB, 57% ultimately received appropriate treatment with second-line
      drugs. The remaining 43% were lost to follow-up (25%), died (14%) or refused
      treatment (4%). CONCLUSION: Resistance to INH+RMP is the most frequent resistance
      pattern among patients referred from DOTS clinics in  the Philippines for
      suspected MDR-TB. Initial use of standard regimens based on national survey data
      and quick uptake of new rapid molecular resistance tests may be useful to reduce
      diagnostic delays and expedite treatment for drug-resistant TB.

PMID- 22863524
TI  - Learning from disease heterogeneity.

PMID- 22863525
TI  - Design, synthesis and evaluation of the inhibitory selectivity of novel trans
      resveratrol analogues on human recombinant CYP1A1, CYP1A2 and CYP1B1.
AB  - A series of trans-stilbene derivatives containing 4'-methylthio substituent were
      synthesized and evaluated for inhibitory activities on human recombinant
      cytochrome P450(s): CYP1A1, CYP1A2, and CYP1B1. CYP1A2-related metabolism of
      stilbene derivatives was estimated by using NADPH oxidation assay. Additionally,
      for CYP1A2 and CYP1B1 molecular docking analysis was carried out to provide
      information on enzyme-ligand interactions and putative site of metabolism. 3,4,5
      Trimethoxy-4'-methylthio-trans-stilbene, an analogue of DMU-212 (3,4,5,4'
      tetramethoxy-trans-stilbene) was an effective inhibitor of all CYP1 enzymes. On
      the other hand, 2,3,4-trimethoxy-4'-methylthio-trans-stilbene, appeared to be the
      most selective inhibitor of the isozymes CYP1A1 and CYP1B1, displaying extremely
      low affinity towards CYP1A2. Molecular modeling suggested that the most probable
      binding poses of the methylthiostilbene derivatives in CYP1A2 active sites are
      those with the methylthio substituent directed towards the heme iron. Products of
      CYP1A2-catalyzed oxidation of 2,4,5-trimethoxy-4'-methylthiostilbene and 3,4,5
      trimethoxy-4'-methylthiostilbene were identified as monohydroxylated compounds.
      Other studied derivatives appeared to be poor substrates of CYP1A2. Structure
      activity relationship analysis rendered better understanding of the mechanism of
      action of xenobiotic-metabolizing enzymes crucial at the early stage of
      carcinogenesis.

PMID- 22863526
TI  - Indole alkaloids from two cultured cyanobacteria, Westiellopsis sp. and
      Fischerella muscicola.
AB  - Chemical investigation of two cultured cyanobacteria, Westiellopsis sp. (SAG
      strain number 20.93) and Fischerella muscicola (UTEX strain number LB1829) led to
      the isolation of three hapalindole-type alkaloids, namely hapalindole X (1),
      deschloro hapalindole I (2), and 13-hydroxy dechlorofontonamide (3), along with
      ten known indole alkaloids (hapalindoles A, C, G, H, I, J, and U, hapalonamide H,
      anhydrohapaloxindole A, and fischerindole L) and fischerellins A and B. The
      structures were determined by a combination of spectroscopic analyses mainly
      based on 1D and 2D NMR and HRESIMS data. Selected compounds were evaluated for
      cytotoxicity and exhibited weak to moderate cytotoxicity against HT-29, MCF-7,
      NCI-H460, SF268, and IMR90 cells. All compounds, except hapalindole C, were
      evaluated for 20S proteasome inhibition and displayed either weak or no
      inhibition at 25 MUg/mL. Selected compounds were also evaluated for antimicrobial
      activity, and hapalindoles X (1) and A, and hapalonamide H showed potent activity
      against both Mycobacterium tuberculosis and Candida albicans with MIC values
      ranging from 0.6 to 2.5 MUM.

PMID- 22863523
TI  - Ovarian cancer and smoking: individual participant meta-analysis including 28,114
      women with ovarian cancer from 51 epidemiological studies.
AB  - BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects
      on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear,
      and the findings from most studies with relevant data are unpublished. To assess
      these associations, we review the published and unpublished evidence. METHODS:
      Eligible epidemiological studies were identified by electronic searches, review
      articles, and discussions with colleagues. Individual participant data for 28,114
      women with and 94,942 without ovarian cancer from 51 epidemiological studies were
      analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in
      smokers compared with never smokers. FINDINGS: After exclusion of studies with
      hospital controls, in which smoking could have affected recruitment, overall
      ovarian cancer incidence was only slightly increased in current smokers compared
      with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17,641
      epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%)
      endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks
      varied substantially across these subtypes (p(heterogeneity)<0.0001). For
      mucinous cancers, incidence was increased in current versus never smokers (1.79,
      95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant
      rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28
      1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only
      borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and
      clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in
      current smokers, and there was no significant association for serous ovarian
      cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary
      significantly by 13 sociodemographic and personal characteristics of women
      including their body-mass index, parity, and use of alcohol, oral contraceptives,
      and menopausal hormone therapy. INTERPRETATION: The excess of mucinous ovarian
      cancers in smokers, which is mainly of tumours of borderline malignancy, is
      roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian
      cancers. The substantial variation in smoking-related risks by tumour subtype is
      important for understanding ovarian carcinogenesis. FUNDING: Cancer Research UK
      and MRC.

PMID- 22863527
TI  - C-N bond formation under Cu-catalysis: synthesis and in vitro evaluation of N
      aryl substituted thieno[2,3-d]pyrimidin-4(3H)-ones against chorismate mutase.
AB  - A series of novel N-aryl substituted thieno[2,3-d]pyrimidin-4(3H)-ones were
      designed and synthesized as potential inhibitors of chorismate mutase. Synthesis
      of this class of compounds was carried out by using Cu-mediated C-N bond forming
      reaction between thieno[2,3-d]pyrimidin-4(3H)-ones and aryl boronic acids. The
      reaction can be performed in an open flask as the conversion was found to be not
      sensitive to the presence of air or atmospheric moisture. A range of compounds
      were prepared by using this method and single crystal X-ray diffraction study was
      performed using a representative compound. In vitro pharmacological data of some
      of the compounds synthesized along with dose response studies using active
      molecules are presented. In silico interactions of these molecules with
      chorismate mutase are also presented.

PMID- 22863528
TI  - Novel structural insights for imidoselenocarbamates with antitumoral activity
      related to their ability to generate methylselenol.
AB  - In the search for molecules with potential antiangiogenic activity we found that
      several imidoselenocarbamate derivatives, which have pro-apoptotic and
      antiproliferative activities, under hypoxic conditions release methylselenol, a
      volatile and highly reactive gas that was considered to be responsible for the
      observed biological activity. The kinetic for the liberation of methylselenol is
      highly dependent on the nature of the overall structure and correlate with their
      proven pro-apoptotic activity in lung cancer cell line H157. The preliminary
      structure-activity relationships allow us to select as the basic structural
      element a scaffold constructed with an imidoselenocarbamate fragment decorated
      with a methyl residue on the Se central atom and two heteroaromatic lateral
      rings. These imidoselenocarbamate derivatives may be of interest both for their
      antitumoral activities and because they have a structure that can be considered
      as a template for the design of new derivatives with apoptotic activity. This
      activity is related to the controlled delivery of methylselenol and makes this an
      interesting approach to develop new antitumoral agents.

PMID- 22863529
TI  - Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.
AB  - A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed
      and synthesized by employing bioisosteric replacement of heterocyclic moieties
      with the amide bond. The structure-activity relationship (SAR) at various
      positions of the scaffold was explored. In this study, a promising compound (S)
      24o with a c-Met IC(50) of 0.022 MUM was identified. The compound exhibited dose
      dependent inhibition of the phosphorylation of c-Met as well as downstream
      signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o
      with c-Met was elucidated by virtue of a molecular modeling study.

PMID- 22863530
TI  - Synthesis and biological evaluation of a fluorescent analog of phenytoin as a
      potential inhibitor of neuropathic pain and imaging agent.
AB  - Here we report on a novel fluorescent analog of phenytoin as a potential
      inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2
      incorporated a heptyl side chain and dansyl moiety onto the parent compound
      phenytoin and produced greater displacement of BTX from sodium channels and
      greater functional blockade with greatly reduced toxicity. Compound 2 reduced
      mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo
      in sensory neuron axons with two-photon microscopy. These results suggest a
      promising strategy for developing novel sodium channel inhibitors with imaging
      capabilities.

PMID- 22863531
TI  - Free fatty acids induce ER stress and block antiviral activity of interferon
      alpha against hepatitis C virus in cell culture.
AB  - BACKGROUND: Hepatic steatosis is recognized as a major risk factor for liver
      disease progression and impaired response to interferon based therapy in chronic
      hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN
      alpha) therapy under the condition of hepatic steatosis is unexplored. We
      investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV)
      replication and IFN-alpha antiviral response in a cell culture model. METHODS:
      Sub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a
      mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty
      acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by
      Nile red staining and electron microscopy then quantified by microfluorometry.
      The effect of FFA treatment on HCV replication and IFN-alpha antiviral response
      was measured by flow cytometric analysis, Renilla luciferase activity, and real
      time RT-PCR. RESULTS: FFA treatment induced dose dependent hepatocellular
      steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed
      by Nile red staining, microfluorometry, and by electron microscopy. Intracellular
      fat accumulation supports replication more in the persistently HCV infected
      culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also
      partially blocked IFN-alpha response and viral clearance by reducing the
      phosphorylation of Stat1 and Stat2 dependent IFN-beta promoter activation. We
      show that FFA treatment induces endoplasmic reticulum (ER) stress response and
      down regulates the IFNAR1 chain of the type I IFN receptor leading to defective
      Jak-Stat signaling and impaired antiviral response. CONCLUSION: These results
      suggest that intracellular fat accumulation in HCV cell culture induces ER
      stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus
      providing an explanation to the clinical observation regarding how hepatocellular
      steatosis influences IFN-alpha response in CHC.

PMID- 22863532
TI  - Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during
      asymmetric satellite stem cell divisions.
AB  - In skeletal muscle, asymmetrically dividing satellite stem cells give rise to
      committed satellite cells that transcribe the myogenic determination factor Myf5,
      a Pax7-target gene. We identified the arginine methyltransferase Carm1 as a Pax7
      interacting protein and found that Carm1 specifically methylates multiple
      arginines in the N terminus of Pax7. Methylated Pax7 directly binds the C
      terminal cleavage forms of the trithorax proteins MLL1/2 resulting in the
      recruitment of the ASH2L:MLL1/2:WDR5:RBBP5 histone H3K4 methyltransferase complex
      to regulatory enhancers and the proximal promoter of Myf5. Finally, Carm1 is
      required for the induction of de novo Myf5 transcription following asymmetric
      satellite stem cell divisions. We defined the C-terminal MLL region as a reader
      domain for the recognition of arginine methylated proteins such as Pax7. Thus,
      arginine methylation of Pax7 by Carm1 functions as a molecular switch controlling
      the epigenetic induction of Myf5 during satellite stem cell asymmetric division
      and entry into the myogenic program.

PMID- 22863533
TI  - Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem
      cells in the mammary gland.
AB  - The mammary epithelium undergoes extensive growth and remodeling during
      pregnancy, suggesting a role for stem cells. Yet their origin, identity, and
      behavior in the intact tissue remain unknown. Using an Axin2(CreERT2) allele, we
      labeled and traced Wnt/beta-catenin-responsive cells throughout mammary gland
      development. This reveals a switch in Wnt/beta-catenin signaling around birth and
      shows that, depending on the developmental stage, Axin2(+) cells contribute
      differently to basal and luminal epithelial cell lineages of the mammary
      epithelium. Moreover, an important difference exists between the developmental
      potential tested in transplantation assays and that displayed by the same cell
      population in situ. Finally, Axin2(+) cells in the adult build alveolar
      structures during multiple pregnancies, demonstrating the existence of a Wnt/beta
      catenin-responsive adult stem cell. Our study uncovers dynamic changes in
      Wnt/beta-catenin signaling in the mammary epithelium and offers insights into the
      developmental fate of mammary gland stem and progenitor cells.

PMID- 22863535
TI  - Leptin triggers Ca(2+) imbalance in monocytes of overweight subjects.
AB  - Obesity is a major risk factor in numerous diseases, in which elevated
      intracellular Ca(2+) plays a major role in increased adiposity. We examined the
      difference between Ca(2+) signals in monocytes of lean and overweight subjects
      and the relationship between leptin induced NADPH oxidase activation and
      intracellular calcium concentration [Ca(2+)](i) homeostasis. Our results are as
      follows: (1) The basal level of [Ca(2+)](i) in resting monocytes of overweight
      subjects (OW monocytes) was higher than that in control cells, whereas the leptin
      induced peak of the Ca(2+) signal was lower and the return to basal level was
      delayed. (2) Ca(2+) signals were more pronounced in OW monocytes than in control
      cells. (3) Using different inhibitors of cellular signaling, we found that in
      control cells the Ca(2+) signals originated from intracellular pools, whereas in
      OW cells they were generated predominantly by Ca(2+)-influx from medium. Finally,
      we found correlation between leptin induced superoxide anion generation and
      Ca(2+) signals. The disturbed [Ca(2+)](i) homeostasis in OW monocytes was fully
      restored in the presence of fluvastatin. Statins have pleiotropic effects
      involving the inhibition of free radical generation that may account for its
      beneficial effect on elevated [Ca(2+)](i) and consequently on the pathomechanism
      of obesity.

PMID- 22863534
TI  - Gene sets identified with oncogene cooperativity analysis regulate in vivo growth
      and survival of leukemia stem cells.
AB  - Leukemia stem cells (LSCs) represent a biologically distinct subpopulation of
      myeloid leukemias, with reduced cell cycle activity and increased resistance to
      therapeutic challenge. To better characterize key properties of LSCs, we employed
      a strategy based on identification of genes synergistically dysregulated by
      cooperating oncogenes. We hypothesized that such genes, termed "cooperation
      response genes" (CRGs), would represent regulators of LSC growth and survival.
      Using both a primary mouse model and human leukemia specimens, we show that CRGs
      comprise genes previously undescribed in leukemia pathogenesis in which multiple
      pathways modulate the biology of LSCs. In addition, our findings demonstrate that
      the CRG expression profile can be used as a drug discovery tool for
      identification of compounds that selectively target the LSC population. We
      conclude that CRG-based analyses provide a powerful means to characterize the
      basic biology of LSCs as well as to identify improved methods for therapeutic
      targeting.

PMID- 22863536
TI  - Differential effects of acute morphine, and chronic morphine-withdrawal on
      obsessive-compulsive behavior: inhibitory influence of CRF receptor antagonists
      on chronic morphine-withdrawal.
AB  - Recent studies have provided convincing evidences for co-morbidity between opioid
      addiction and obsessive-compulsive disorder (OCD), and the involvement of the
      corticotrophin-releasing factor (CRF) in the effects of morphine-withdrawal. Some
      scanty evidences also point towards the role of CRF in OCD and related disorders.
      But, no evidence indicated the role of CRF in morphine withdrawal associated
      obsessive-compulsive behavior (OCB). Therefore, the present study investigated
      the role of CRF in morphine-withdrawal induced OCB in mice. Marble-burying
      behavior in mice was used to assess OCB as this model has good predictive and
      face validity. The results revealed that acute morphine dose dependently
      attenuated the marble burying behavior, whereas withdrawal of chronic morphine
      was associated with significant rise in marble burying behavior. This indicates
      the differential effect of acute morphine and chronic morphine-withdrawal on OCB.
      Further, acute treatment with CRF receptor antagonists like antalarmin (2 and 4
      MUg/mouse, i.c.v.) or astressin-2B (3 and 10 nmol/mouse, i.c.v.) dose dependently
      attenuated the peak morphine-withdrawal induced increase in marble burying
      behavior. Moreover, concomitant treatment with antalarmin (4 MUg/mouse, i.c.v.)
      or astressin-2B (10 nmol/mouse, i.c.v.) along with morphine blocked the morphine
      withdrawal associated exacerbation of OCB. These results indicate that OCB
      associated with morphine withdrawal state is partly mediated by the activation of
      central CRF receptors.

PMID- 22863537
TI  - Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma
      progression in male mice.
AB  - Hepatocellular carcinoma (HCC) is a global health burden with limited treatment
      options and poor prognosis. Silibinin, an antioxidant derived from the Milk
      Thistle plant (Silybum marianum), is reported to exert hepatoprotective and
      antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and
      proliferation. Using a DEN-initiated mouse model of HCC, this study examined the
      effects of dietary silibinin supplementation alone, or in combination with
      chronic ethanol consumption on HCC progression. Our data demonstrate silibinin
      exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis
      but, when co-administered with ethanol, exacerbated the promotional effects of
      ethanol in HCC bearing mice, but only in males.

PMID- 22863538
TI  - Synergistic effect of panobinostat and bortezomib on chemoresistant acute
      myelogenous leukemia cells via AKT and NF-kappaB pathways.
AB  - In this study, we investigated the synergistic effects of panobinostat and
      bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute
      myelogenous leukemia (AML) primary cells. Combination of both agents had
      synergistic cytotoxicity on these cells, and increased the sensitivity of
      HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate
      multiple apoptotic and drug metabolic related molecules, including activation of
      caspases, down-regulation of XIAP, Bcl-2 and MRP1. These effects were likely to
      be mediated via inhibition of AKT and NF-kappaB pathways. These findings provide
      evidence for clinic protocols using panobinostat and borezomib to overcome drug
      resistance in refractory AML patients.

PMID- 22863539
TI  - Inhibition of autophagy and induction of breast cancer cell death by mefloquine,
      an antimalarial agent.
AB  - Autophagy has been recognized as a potential target for cancer therapy. The
      antimalarial drug chloroquine (CQ) is able to inhibit autophagy and therefore is
      being considered for cancer therapeutics. However, the relatively low potency of
      CQ prompted us to investigate whether other lysosomotropic agents might be more
      effective, and thus potentially more useful. We therefore compared the cytotoxic
      efficacy of CQ, the quinoline analog mefloquine (MQ), and the fluoroquinolones
      ciprofloxacin and levofloxacin in several human breast cancer cell lines. We
      found that MQ was the most potent compound tested; it inhibited autophagy,
      triggered endoplasmic reticulum stress, and caused cell death in T47D and MDA-MB
      231. Altogether, our study demonstrates superior potency of MQ over CQ and the
      ability of MQ to produce anticancer effects in both hormone receptor positive and
      negative breast cancer cell lines, suggesting its usefulness in treating various
      types of cancer.

PMID- 22863540
TI  - Written exposure as an intervention for PTSD: a randomized clinical trial with
      motor vehicle accident survivors.
AB  - The present study examined the efficacy of a brief, written exposure therapy
      (WET) for posttraumatic stress disorder (PTSD). Participants were 46 adults with
      a current primary diagnosis of motor vehicle accident-related PTSD. Participants
      were randomly assigned to either WET or a waitlist (WL) condition. Independent
      assessments took place at baseline and 6-, 18-, and 30-weeks post baseline (WL
      condition not assessed at 30 weeks). Participants assigned to WET showed
      significant reductions in PTSD symptom severity at 6- and 18-week post-baseline,
      relative to WL participants, with large between-group effect sizes. In addition,
      significantly fewer WET participants met diagnostic criteria for PTSD at both the
      6- and 18-week post-baseline assessments, relative to WL participants. Treatment
      gains were maintained for the WET participants at the 30-week post baseline
      assessment. Notably, only 9% of participants dropped out of WET and the WET
      participants reported a high degree of satisfaction with the treatment. These
      findings suggest that a brief, written exposure treatment may efficaciously treat
      PTSD. Future research should examine whether WET is efficacious with other PTSD
      samples, as well as compare the efficacy of WET with that of evidence-based
      treatments for PTSD.

PMID- 22863543
TI  - Common laboratory tests predict imminent death in ward patients.
AB  - OBJECTIVE: To estimate the ability of commonly measured laboratory variables to
      predict an imminent (within the same or next calendar day) death in ward
      patients. DESIGN: Retrospective observational study. SETTING: Two university
      affiliated hospitals. PATIENTS: Cohort of 42,701 patients admitted for more than
      24 hours and external validation cohort of 13,137 patients admitted for more than
      24 hours. INTERVENTION: We linked commonly measured laboratory tests with event
      databases and assessed the ability of each laboratory variable or combination of
      variables together with patient age to predict imminent death. MEASUREMENTS AND
      MAIN RESULTS: In the inception teaching hospital, we studied 418,897 batches of
      tests in 42,701 patients (males 55%; average age 65.8 +/- 17.6 years), for a
      total of >2.5 million individual measurements. Among these patients, there were
      1596 deaths. Multivariable logistic modelling achieved an AUC-ROC of 0.87 (95%
      CI: 0.85-0.89) for the prediction of imminent death. Using an additional 105,074
      batches from a cohort of 13,137 patients from a second teaching hospital, the
      multivariate model achieved an AUC-ROC of 0.88 (95% CI: 0.85-0.90). CONCLUSIONS:
      Commonly performed laboratory tests can help predict imminent death in ward
      patients. Prospective investigations of the clinical utility of such predictions
      appear justified.

PMID- 22863541
TI  - A cognitive model of pathological worry.
AB  - We present an evidence-based model of pathological worry in which worry arises
      from an interaction between involuntary (bottom-up) processes, such as habitual
      biases in attention and interpretation favouring threat content, and voluntary
      (top-down) processes, such as attentional control. At a pre-conscious level,
      these processes influence the competition between mental representations when
      some correspond to the intended focus of attention and others to threat
      distracters. Processing biases influence the probability of threat
      representations initially intruding into awareness as negative thoughts. Worry in
      predominantly verbal form then develops, influenced by conscious processes such
      as attempts to resolve the perceived threat and the redirection of attentional
      control resources to worry content, as well as the continuing influence of
      habitual processing biases. After describing this model, we present evidence for
      each component process and for their causal role in pathological worry, together
      with implications for new directions in the treatment of pathological worry.

PMID- 22863544
TI  - The subdural evacuation port system: outcomes from a single institution
      experience and predictors of success.
AB  - INTRODUCTION: Numerous surgical options for treatment of chronic subdural
      hematomas (cSDH) exist. Several reports have examined the Subdural Evacuating
      Port System (SEPS), a variation of the twist drill craniotomy (TDC) technique.
      Although high success rates have been reported, a significant portion of patients
      treated with SEPS fail and require additional procedures. This report examines
      the largest single institution experience with the SEPS and explores patient and
      imaging characteristics associated with successful procedures. METHODS: A
      retrospective chart review was performed to identify all patients who have
      undergone SEPS drainage of cSDH. Demographic and radiographic characteristics
      were evaluated. Demographic data included patient's age, sex, presenting
      symptoms, pre-procedural GCS score, and use of anticoagulation or antiplatelet
      agents. The volume of drainage per procedure and radiographic data including
      laterality, density, and maximal diameter of the collection, presence of
      septations, midline shift, resolution of the collection 3 weeks post procedure,
      and measurements to assess atrophy were collected. Total length of stay and time
      in the intensive care unit was also recorded. Results were classified as a
      success or failure based on the need for additional procedures including
      craniotomy or burr hole craniotomy in the operating room. Patients treated with
      two SEPS procedures during the same hospitalization and no other procedures were
      included in the success group for statistical analyses. RESULTS: 171 subdural
      collections were treated in 159 patients (147 unilateral and 12 bilateral). One
      hundred thirty three collections (77.8%) were successfully drained. In a
      comparison of the success and failure groups, there were no statistically
      significant differences (p<0.05) in the patients' mean age, sex, presenting
      Glasgow Coma Scale score, coagulation profile, presenting symptoms (except
      altered mental status and language disturbance), subdural diameter or laterality,
      midline shift, presence of atrophy, density of most acute portion, or time in
      hospital. In the success group, there was a shorter mean stay in the intensive
      care unit (S: 4.1+/-4.5 days vs F: 5.4+/-4.6 days; p=0.03) and a larger output
      drained (S: 131.1+/-71.2ml vs F: 99.0+/-84.2ml; p=0.04). Success was less likely
      with mixed density collections (S: 38.2% vs F: 64.3%; p=0.02) and with
      collections containing greater than 2 intrahematomal septations (S: 17.1% vs F:
      40.7%; p=0.007). In successful cases, mean volumes for collections prior to SEPS,
      immediately after SEPS, and on delayed scans (>=30 days since SEPS placement) the
      respective volumes were 83.1+/-35.1ml, 41.5+/-23.2ml, and 37.9+/-26.5ml. Both
      post-SEPS volumes were less than the pre-SEPS volume (p<0.0001). 76.0% of
      patients with delayed scans had complete resolution of cSDH or minimal residual
      cSDH with no local mass effect on the most recent imaging. The mean period of
      follow-up imaging was 95.6+/-196.2 days. Only one patient in our series required
      an emergent craniotomy following immediate complications from SEPS placement.
      CONCLUSIONS: The SEPS is an effective, safe, and durable treatment for cSDH.
      Although we consider the SEPS a first-line treatment for the majority of patients
      with cSDH, management of cSDH must be tailored to each patient. In mixed density
      collections with large proportions of acute hemorrhage and in collections with
      numerous intrahematomal septations, alternative surgical techniques should be
      considered as first-line therapies.

PMID- 22863545
TI  - Giant cell myocarditis: clinical and pathological features in an Indian
      population.
AB  - BACKGROUND: Giant cell myocarditis (GCM) is a rare disorder that is known
      primarily from North American, European, and Japanese case series. The clinical
      and pathological features of GCM in India have not been reported. METHODS: We
      reviewed the pathology records from 1994 to 2010 from a tertiary care referral
      hospital in Mumbai for all cases of pathologically confirmed GCM. Gross and
      microscopic histological features and clinical characteristics of the GCM cases
      were described and qualitatively compared to GCM case series from other regions
      of the world. RESULTS: The 12 cases of GCM constituted 0.005% of all autopsies
      and 0.8% of myocarditis cases. Gross pathological features included variably
      dilated chambers in 8/12 cases with multifocal involvement of the myocardium.
      Three had regional hypertrophy associated with marked lymphocytic infiltrate.
      There were unique cases of a posterior wall rupture with hemopericardium and a
      case with multiple epicardial inflammatory sessile polyps. A novel possible
      trigger was suggested by a positive serologic test for leptospirosis in one case.
      The clinical features including age, gender, presenting symptoms, and prognosis
      resemble those reported in autopsy-based case series from other regions.
      CONCLUSIONS: GCM affects patients in India at approximately the same rate as in
      Europe and Japan. The clinical and histological features of GCM are similarly
      severe and suggest a heart-specific autoimmune reaction.

PMID- 22863547
TI  - Synthesis, spectroscopic characterization, antimicrobial, DNA binding and
      oxidative-induced DNA cleavage activities: new oxovanadium(IV) complexes of 2-(2
      hydroxybenzylideneamino)isoindoline-1,3-dione.
AB  - A mononuclear complex [(phen)VO(bid)]SO(4).3H(2)O (1), (phen=1,10-phenanthroline)
      and a binuclear [(VObid)(2)].H(2)O (2), with Hbid [(E)-2-(2
      hydroxybenzylideneamino)isoindoline-1,3-dione] were prepared and characterized by
      elemental analysis, IR, mass, UV-Vis spectral studies, ESR, molar conductance and
      thermogravimetric analysis. The DNA-binding properties of the complexes 1 and 2
      were investigated by UV-spectroscopy, fluorescence spectroscopy and viscosity
      measurements. The superoxide dismutase-like activity of the complexes has been
      determined. The spectral results suggest that the complexes 1 and 2 can bind to
      DNA by intercalation. The cleavage properties of these complexes with super
      coiled pUC19 have been studied using the gel electrophoresis method, where both
      complexes 1 and 2 displayed chemical nuclease activity in the absence and
      presence of H(2)O(2)via an oxidative mechanism. All the complexes inhibit the
      growth of both Gram positive and Gram negative bacteria to competent level.
      Minimum inhibitory concentration (MIC) was determined by microtiter method.

PMID- 22863549
TI  - White matter tract abnormalities in first-episode psychosis.
AB  - Fibers connecting fronto-temporal and fronto-medial structures that pass through
      the anterior limb of the internal capsule (ALIC) subserve executive and
      psychomotor functioning. Both of these functions are adversely affected in
      schizophrenia, and may be abnormal at illness onset. In a study of first-episode
      psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to
      examine ALIC integrity. Fourteen early psychosis patients and 29 healthy
      volunteers were included. Symptoms were assessed with the Positive and Negative
      Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE
      Signa 1.5T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was
      acquired for manual seeding in structural space. Diffusion tensor imaging (DTI)
      was performed, and all DTI images were co-registered to structural space. Seeds
      were manually drawn bilaterally on the coronal plane at a specified location.
      Diffusion images were post-processed for subsequent Tract-based Spatial
      Statistics (TBSS) analysis. First-episode psychosis patients had significantly
      smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy
      volunteers on the left and the right (p-values<0.04). No differences in mean
      fractional anisotropy (FA) were seen within either left or right tracts (p
      values>0.05), nor did TBSS reveal any other differences in FA values between
      groups in other regions. Relationships between tract volumes and symptom severity
      were not observed in this study.

PMID- 22863548
TI  - A broken filter: prefrontal functional connectivity abnormalities in
      schizophrenia during working memory interference.
AB  - Characterizing working memory (WM) abnormalities represents a fundamental
      challenge in schizophrenia research given the impact of cognitive deficits on
      life outcome in patients. In prior work we demonstrated that dorsolateral
      prefrontal cortex (DLPFC) activation was related to successful distracter
      resistance during WM in healthy controls, but not in schizophrenia. Although
      understanding the impact of regional functional deficits is critical, functional
      connectivity abnormalities among nodes within WM networks may constitute a final
      common pathway for WM impairment. Therefore, this study tested the hypothesis
      that schizophrenia is associated with functional connectivity abnormalities
      within DLPFC networks during distraction conditions in WM. 28 patients and 24
      controls completed a delayed non-verbal WM task that included transient visual
      distraction during the WM maintenance phase. We computed DLPFC whole-brain task
      based functional connectivity (tb-fcMRI) specifically during the maintenance
      phase in the presence or absence of distraction. Results revealed that patients
      failed to modulate tb-fcMRI during distracter presentation in both cortical and
      sub-cortical regions. Specifically, controls demonstrated reductions in tb-fcMRI
      between DLPFC and the extended amygdala when distraction was present. Conversely,
      patients failed to demonstrate a change in coupling with the amygdala, but showed
      greater connectivity with medio-dorsal thalamus. While controls showed more
      positive coupling between DLPFC and other prefrontal cortical regions during
      distracter presentation, patients failed to exhibit such a modulation. Taken
      together, these findings support the notion that observed distracter resistance
      deficit involves a breakdown in coupling between DLPFC and distributed regions,
      encompassing both subcortical (thalamic/limbic) and control region connectivity.

PMID- 22863551
TI  - Clutch size and egg volume in great tits (Parus major) increase under low
      intensity electromagnetic fields: a long-term field study.
AB  - Exposure to electromagnetic fields (EMFs) can affect a wide range of biological
      processes, including reproduction, growth and development. Experiments aimed at
      investigating the biological effects of EMFs, focused on potential harmful
      effects on humans, have been mostly carried out in vitro or with animal models in
      laboratory conditions. By contrast, studies performed on wild animals are scarce.
      The effects of EMFs created by an electric power line on reproductive traits of a
      wild great tit (Parus major) population were explored by analysing data gathered
      during nine breeding seasons. EMF exposure significantly increased clutch size
      (7%) and egg volume (3%), implying a 10% increase in clutch volume. This
      indicates an increase in reproductive investment from parent birds exposed to
      EMFs as compared to the adjacent reference area. These results cannot be
      attributed to habitat or adult quality differences between the exposed and
      reference group. Nevertheless, no differences in hatching success or final
      productivity (fledging and reproductive success or nestling body mass) could be
      detected. Our study clearly shows that EMFs created by power lines can have
      biological consequences in wild organisms that live intimately with them. To our
      knowledge, this is the first study showing an increase in clutch size, and one of
      the few reporting an increase in egg size, associated with EMF exposure. The
      possible mechanisms by which great tits invest more under EMF exposure are
      discussed, and future research directions to evaluate the effect of EMFs on avian
      reproduction in the wild are suggested.

PMID- 22863550
TI  - Reduced fractional anisotropy and axial diffusivity in white matter in 22q11.2
      deletion syndrome: a pilot study.
AB  - Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of
      schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without
      schizophrenia to a group of matched healthy controls using Tract-Based-Spatial
      Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and
      Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left
      parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity)
      were observed. Of note, studies in chronic schizophrenia patients report reduced
      FA, no changes in AD, and increases in RD in WM. Our findings suggest different
      WM microstructural pathology in 22q11.2DS than in patients with schizophrenia.

PMID- 22863553
TI  - Current research status of endoscopic submucosal dissection for colorectal
      neoplasms.
AB  - Endoscopic submucosal dissection (ESD) has been applied to, and gradually
      standardized for, early gastric cancers; however, it has not yet been widely used
      for treatment of colorectal neoplasms. Compared with gastric ESD, the thinner
      colorectal wall and winding nature of the colon make colorectal ESD a much more
      difficult operative technique. Despite greater risks of postoperative
      complications, particularly perforation of the colon, more and more endoscopists
      are making an effort to study this new technique in terms of its capability of
      larger neoplastic resection, higher en bloc resection rate and lower local
      recurrence rate of neoplasms in comparison with other endoscopic treatments.
      Thus, colorectal ESD may become the standard treatment for early colorectal
      neoplasms in the future. This review article discusses the current research on
      endoscopic submucosal dissection for colorectal neoplasms.   Please see
      supplementary files for the accompanying video ESD with snare.

PMID- 22863552
TI  - Household mold and dust allergens: exposure, sensitization and childhood asthma
      morbidity.
AB  - BACKGROUND: Few studies address concurrent exposures to common household
      allergens, specific allergen sensitization and childhood asthma morbidity.
      OBJECTIVE: To identify levels of allergen exposures that trigger asthma
      exacerbations in sensitized individuals. METHODS: We sampled homes for common
      indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f
      1) and cockroach (Bla g 1)) for levels associated with respiratory responses
      among school-aged children with asthma (N=1233) in a month-long study. Blood
      samples for allergy testing and samples of airborne fungi and settled dust were
      collected at enrollment. Symptoms and medication use were recorded on calendars.
      Combined effects of specific allergen sensitization and level of exposure on
      wheeze, persistent cough, rescue medication use and a 5-level asthma severity
      score were examined using ordered logistic regression. RESULTS: Children
      sensitized and exposed to any Penicillium experienced increased risk of wheeze
      (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough
      (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI
      1.06, 3.72) compared to those not sensitized or sensitized but unexposed.
      Children sensitized and exposed to pet allergen were at significantly increased
      risk of wheeze (by 39% and 53% for Fel d 1>0.12 MUg/g and Can f 1>1.2 MUg/g,
      respectively). Increased rescue medication use was significantly associated with
      sensitization and exposure to Der p 1>0.10 MUg/g (by 47%) and Fel d 1>0.12 MUg/g
      (by 32%). CONCLUSION: Asthmatic children sensitized and exposed to low levels of
      common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at
      significant risk for increased morbidity.

PMID- 22863554
TI  - Zoledronic acid, an aminobisphosphonate, prolongs survival of skin allografts.
AB  - PURPOSE: Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate
      used to prevent excessive bone loss in clinical practice, has been shown to
      affect the development of dendritic cells by redirecting differentiation toward a
      state of atypical maturation. The study was aimed to examine whether ZOL can
      reduce acute rejection of skin allografts. METHODS: A skin transplantation model
      using C57BL/6 to BALB/c mice was used. ZOL was injected intraperitoneally into
      transplant recipients post-surgically. Graft survival, body weight, leukocyte
      count, hepatic and renal functions were assessed. RESULTS: ZOL treatment
      significantly prolonged skin allograft survival in mice. In terms of toxicity,
      there were no significant differences in body weight, leukocyte count, plasma
      alanine aminotransferase or creatinine levels between the ZOL-treated and control
      groups. Histopathology showed that the loss of skin integrity seen in control
      group was prevented by ZOL treatment. In draining lymph nodes and spleen, the
      number and clustering extent of mononuclear cells were markedly declined by ZOL
      treatment. The plasma IL-6 levels were reduced by treatment of ZOL. CONCLUSION:
      ZOL can prolong skin allograft survival without major toxicity.

PMID- 22863555
TI  - Plasma biomarkers and cystic fibrosis lung disease.
AB  - PURPOSE: The purpose of this study was to determine whether plasma biomarkers
      reflect changes in lung function and respiratory exacerbations associated with CF
      lung disease. METHODS: Plasma human leukocyte elastase/alpha1 antitrypsin complex
      (pHLE complex) values were measured in 28 adult CF patients and 47 healthy
      volunteers and correlated with forced expiratory volume (FEV1) and forced vital
      capacity (FVC). pHLE complexes were studied during respiratory exacerbations and
      after antibiotic therapy. Plasma cytokines and sialic acid were also measured.
      RESULTS: pHLE complexes were increased in CF patients (p < 0.01), were inversely
      correlated with FEV1 (r = 0.71) and FVC (r = 0.67) and returned to normal levels
      after intravenous antibiotics (p < 0.001). Plasma cytokines did not correlate
      with lung function. Total sialic acid increased during CF respiratory
      exacerbations and decreased after antibiotic therapy. CONCLUSION: Plasma sialic
      acid and pHLE complexes reflect clinically meaningful changes in CF lung disease.
      In contrast, plasma cytokine levels did not correlate with lung function.

PMID- 22863556
TI  - BAP1 is a good prognostic factor in advanced non-small cell lung cancer.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) is the leading worldwide source of
      cancer-related deaths. Although some drugs targeting epidermal growth factor
      receptor (EGFR) mutations have been developed, most advanced NSCLC is still
      incurable and new targets for anticancer drugs are in demand. BRCA1-associated
      protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS). UPS has
      emerged as a potential target for anticancer drugs. The aim of the present study
      was to investigate the expression of BAP1 protein in patients with NSCLC.
      METHODS: BAP1 expression was measured using Western blot analysis in 103 cases
      patients with advanced NSCLC. RESULTS: Results revealed 49 (47.5%) patients were
      classified with high expression of BAP1. Squamous cell carcinomas were more
      likely to be observed in BAP1 high expressers compared with adenocarcinomas
      (55.8% vs. 32.3%, p = 0.001). High BAP1 expression was associated with no lymph
      node metastasis (p = 0.002). There was also a significant association between
      BAP1 expression and histological type (p = 0.014), while expression of BAP1 was
      not correlated with other clinical or pathological characteristics. Kaplan-Meier
      survival analysis showed that patients with high BAP1 expression had a longer
      median survival compared with patients with low BAP1 expression (23.2 vs. 14.7
      months, p = 0.021). Multivariate analysis revealed that high BAP1 expression was
      an independent lower risk for all 103 patients (HR = 0.61, 95% CI 0.32-0.71, p =
      0.003). CONCLUSIONS: BAP1 may be a useful prognostic factor of NSCLC patients and
      potential target for anticancer drugs.

PMID- 22863557
TI  - Effects of long-term low-level solvent exposure on cognitive function.
AB  - PURPOSE: The effects of long-term low-level exposures to solvents on cognitive
      function were investigated. METHODS: A total of 389 workers at a gun factory,
      those exposed to solvents (n = 193) and those that were not exposed to solvents
      during work (n = 196), were included. All the workers were given a questionnaire.
      Cognitive function was evaluated by Mini-mental Status Examination (MMSE) and
      psychological status was assessed by Hospital Anxiety and Depression (HAD) Scale.
      RESULTS: No differences were found in the MMSE and HAD scores between solvent
      exposed workers and control workers (p > 0.05). In the workers who had used a
      mask for a longer time, orientation scores were lower. Daytime sleepiness was
      related to lower recall scores. Left-handed workers had higher total HAD scores
      than right-handed workers. CONCLUSIONS: Long-term low-level exposure to solvents
      did not affect cognitive function in the workers, according to their MMSE scores.
      Duration of solvent exposure was also not related to MMSE Scores. Short sleep
      duration and daytime sleepiness may negatively affect cognitive function.

PMID- 22863558
TI  - Association of serum fetuin-A levels with heart valve calcification and other
      biomarkers of inflammation among persons with acute coronary syndrome.
AB  - PURPOSE: Fetuin-A is a multifunctional hepatic secretory protein that inhibits
      dystrophic vascular and valvular calcification. Our aim was to evaluate the
      relationship among fetuin-A levels, heart valve calcification and other
      biomarkers of inflammation in patients with acute coronary syndrome (ACS).
      METHODS: The associations among serum fetuin-A concentrations, mitral annular
      (MAC) and aortic valve calcification and other biomarkers of inflammation (hs
      CRP, ferritin, fibrinogen, white blood cell count (WBC), erythrocyte
      sedimentation rate (ESR), albumin levels) were evaluated in ACS patients and
      healthy controls. The study included 95 patients (mean age 61.8 +/- 12.10 years)
      and 81 healthy controls (mean age 48.33 +/- 9.19 years). RESULTS: Fetuin-A levels
      were significantly lower in patients with ACS than in healthy controls (0.76 +/-
      0.23 and 1.10 +/- 0.45 g/L, respectively; p < 0.001). Fetuin-A was lower in
      patients with mitral annular calcification (p = 0.007) and aortic (p = 0.001)
      valve calcification. In patients with ACS, there was a negative correlation among
      serum urea (r = -0.377; p < 0.001) and creatinine (r = -0.232; p = 0.024) levels
      and fetuin-A, and a negative correlation among WBC (r = -0.156; p = 0,132), ESR
      (r = -0.214; p = 0.037), hs-CRP (r = -0.220; p = 0.032) levels and fetuin-A. A
      positive correlation was seen between albumin and fetuin-A (r = 0.362; p <
      0.001). Multivariate logistic regression analysis revealed that fetuin-A was the
      variable that had a significant effect on ACS (p = 0.020 OR = .015; (95%
      CI)(0.000-0.520). CONCLUSION: Fetuin-A levels decrease in patients with acute
      coronary syndromes, independent of heart valve calcification. Fetuin-A may
      therefore act as a negative acute phase protein after myocardial infarction.

PMID- 22863559
TI  - A comparison of the application of fibrin glue and adhesive film for repair of
      anastomotic leaks in the rat.
AB  - BACKGROUND: Anastomotic leaks constitute one of the most serious intraoperative
      complications and although many studies have been devoted to finding a solution
      for this problem, none of them has yet been able offer a decisive, successful
      method. In this study, the ability of fibrin glue and adhesive film to repair
      anastomotic leaks in an experimental model was compared. MATERIALS AND METHODS:
      The sample comprised four groups of seven rats: Group 1 (Control): the distal
      colon was transected and anastomosis was performed. Group 2 (Primary repair):
      incomplete anastomosis produced a leak that was closed by primary repair on day
      3. Group 3 (Fibrin glue): incomplete anastomosis produced a leak that was closed
      by primary repair and fibrin glue applied on day 3. Group 4 (Adhesive film):
      incomplete anastomosis produced a leak that was closed by primary repair and
      adhesive film was applied on day 3. The rats were sacrificed on day 6 following
      anastomosis. Anastomotic blast compressions were measured and fibroblast
      activation, inflammation, neovascularization and levels of collagen were
      evaluated. RESULTS: The results from Group 4 showed that blast compression values
      were high and statistically significantly increased over control values (p <
      0.05). Inflammation in Group 2 was significantly higher than the other groups (p
      < 0.05). No significant differences were detected in the comparison of the groups
      regarding the other scoring criteria (p > 0.05). CONCLUSION: Adhesive film is
      more effective in reducing anastomotic leakage than fibrin glue.

PMID- 22863560
TI  - Serum CA-125: biomarker of pulmonary tuberculosis activity and evaluation of
      response to treatment.
AB  - PURPOSE: CA-125 is a high molecular weight mucin-like glycoprotein and an ovarian
      cancer antigen. Elevated CA-125 levels are also seen with various other benign
      and malignant conditions. In this study, the ability of CA-125 to predict
      pulmonary tuberculosis activity was investigated. METHODS: This analytical study
      included 42 cases with active tuberculosis (Group 1), 35 cases with inactive
      tuberculosis (Group 2) and 20 healthy subjects (Group 3). CA-125 measurements
      were taken in all three groups. Measurements in Group 1 were repeated after
      completing a two month anti-tuberculosis treatment in 38 of the 42 patients.
      RESULTS: Mean serum CA-125 level for Group 1 was 76.48 +/- 24.71 U/mL, which was
      significantly higher than levels in Group 2 (20.01 +/- 7.89 U/mL) and Group 3
      (18.32 +/- 2.87 U/mL) (p < 0.001). Of the 38 patients in Group 1 who were studied
      both pre- and post-treatment, CA-125 levels decreased significantly: from 78.88
      +/- 24.72 U/mL before treatment to 22.78 +/- 8.02 U/mL after treatment (p <
      0.001). There was no statistically significant difference between the post
      treatment values of Group 1 and either Group 2 and Group 3 values (p > 0.05).
      Group 2 and Group 3 levels were not significantly different (p > 0.05). The cut
      off level for accurate determination of activity was 36.35 U/mL. The sensitivity
      at this level was 97.6% and specificity was 100%. CONCLUSION: Our findings
      suggest that CA-125 can be a beneficial parameter in determination of pulmonary
      tuberculosis activity and the evaluation of response to treatment.

PMID- 22863561
TI  - Effect of overweight and obesity on the left ventricular systolic and diastolic
      functions in patients with acute myocardial infarction.
AB  - PURPOSE: The purpose of this study was to evaluate whether a association exits
      among overweight and obesity and left ventricular systolic and diastolic
      functions in patients admitted with first ST-elevation myocardial infarction
      (STEMI). METHODS: The present study was performed on 451 consecutive patients
      diagnosed with first STEMI (376 men, 75 women; mean age 56.1 +/- 10.8 years). The
      patients were classified into three groups based on their body mass index (BMI)
      as normal weight (BMI < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2) and obese (BMI
      > 30 kg/m2). Echocardiographic features were evaluated and compared among the
      three groups. RESULTS: Mitral annulus E velocities were higher in obese
      individuals than normal weight group (p < 0.01). In contrast, mitral A velocities
      were lower (p =0.03); consequently, E?A and E'?A' ratios were lower (both p =
      0.01) in the obese group with respect to normal weight group. When the correction
      of entire variations existing among the groups were performed using multivariate
      linear regressions analyses, it turned out that BMI was independently associated
      with E/A (beta = -0.19, p = 0.044) and with E'/A' (beta = -0.016, p = 0.021).
      Ejection fraction, wall motion score index and myocardial S velocities were
      comparable among the study groups (p > 0.05). CONCLUSION: These results suggest
      that while obesity has no adverse effect on the left ventricular systolic
      function, it has unfavorable consequences on the left ventricular diastolic
      function in the patients with first STEMI. In contrast, no unfavorable effects of
      overweight on the left ventricular systolic and diastolic function were detected.

PMID- 22863563
TI  - Differences in volatile terpene composition between the bark and leaves of
      tropical tree species.
AB  - Volatile terpenes are among the most diverse class of defensive compounds in
      plants, and they are implicated in both direct and indirect defense against
      herbivores. In terpenes, both the quantity and the diversity of compounds appear
      to increase the efficiency of defense as a diverse blend of compounds provides a
      more efficient protection against a broader range of herbivores and limits the
      chances that an enemy evolves resistance. Theory predicts that plant defensive
      compounds should be allocated differentially among tissues according to the value
      of the tissue, its cost of construction and the herbivore pressure on it. We
      collected volatile terpenes from bark and leaves of 178 individual tree belonging
      to 55 angiosperm species in French Guiana and compare the kind, amount, and
      diversity of compounds in these tissues. We hypothesized that in woody plants,
      the outermost part of the trunk should hold a more diverse blend of volatile
      terpenes. Additionally, as herbivore communities associated with the leaves is
      different to the one associated with the bark, we also hypothesized that terpene
      blends should be distinct in the bark vs. the leaves of a given species. We found
      that the mixture of volatile terpenes released by bark is different and more
      diverse than that released by leaves, both in monoterpenes and sesquiterpenes.
      This supports our hypothesis and further suggests that the emission of terpenes
      by the bark should be more important for trunk defense than previously thought.

PMID- 22863562
TI  - PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American
      population.
AB  - PURPOSE: This study examined genetic associations of patatin-like phospholipase
      domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an
      extensively documented, randomly recruited Mexican American population at high
      risk of liver disease. METHODS: Two single nucleotide polymorphisms (SNP) in the
      PNPLA3 gene (i.e., rs738409 and rs2281135) were genotyped in 1532 individuals.
      Population stratification was corrected by the genotyping of 103 ancestry
      informative markers (AIMs) for Mexican Americans. RESULTS: Both PNPLA3 SNPs
      showed highly significant association with alanine aminotransferase (ALT) levels,
      but was also, in males, associated with aspartate aminotransferase (AST) levels.
      Haplotypic association test of the two SNPs suggested stronger genetic
      association with rs738409 than rs2281135. Obvious sex effects were observed:
      rs738409-sex interaction in ALT levels P = 8.37 x 10(-4); rs738409-sex
      interaction in AST levels P = 5.03 x 10(-3). CONCLUSIONS: This population study
      highlights a sex-specific association of PNPLA3 polymorphisms and elevated liver
      enzymes in a population-based study, independent of common pathological factors
      of the metabolic syndrome. The strong genetic association found in women <= 50
      years old, but not in women > 50 years old, suggests that sex hormones may
      mediate the sex effect.

PMID- 22863564
TI  - Biochemical characterization and kinetic properties of alanine aminotransferase
      homologues partially purified from wheat (Triticum aestivum L.).
AB  - Four homologues of alanine aminotransferase have been isolated from shoots of
      wheat seedlings and purified by saline precipitation, gel filtration, preparative
      electrophoresis and anion exchange chromatography on Protein-Pak Q 8HR column
      attached to HPLC. Alanine aminotransferase 1 (AlaAT1) and 2 (AlaAT2) were
      purified 303- and 452-fold, respectively, whereas l-glutamate: glyoxylate
      aminotransferase 1 (GGAT1) and 2 (GGAT2) were purified 485- and 440-fold,
      respectively. Consistent inhibition of AlaAT (EC 2.6.1.2) and GGAT (EC 2.6.1.4)
      activities by p-hydroxymercuribenzoate points on participation of cysteine
      residues in the enzyme activity. The molecular weight of AlaAT1 and AlaAT2 was
      estimated to be 65kDa and both of them are monomers in native state.
      Nonsignificant differences between K(m) using alanine as substrate and catalytic
      efficiency (k(cat)/K(m)) for l-alanine in reaction with 2-oxoglutarate indicate
      comparable kinetic constants for AlaAT1 and AlaAT2. Similar kinetic constants for
      l-alanine in reaction with 2-oxoglutarate and for l-glutamate in reaction with
      pyruvate for all four homologues suggest equally efficient reaction in both
      forward and reverse directions. GGAT1 and GGAT2 were able to catalyze
      transamination between l-glutamate and glyoxylate, l-alanine and glyoxylate and
      reverse reactions between glycine and 2-oxoglutarate or pyruvate. Both GGATs also
      consisted of a single subunit with molecular weight of about 50kDa. The estimated
      K(m) for GGAT1 (3.22M) and GGAT2 (1.27M) using l-glutamate as substrate was lower
      in transamination with glyoxylate than with pyruvate (9.52 and 9.09mM,
      respectively). Moreover, distinctively higher values of catalytic efficiency for
      l-glutamate in reaction with glyoxylate than for l-glutamate in reaction with
      pyruvate confirm involvement of these homologues into photorespiratory
      metabolism.

PMID- 22863565
TI  - Restricted spirometry in the Burden of Lung Disease Study.
AB  - BACKGROUND: The presence of restrictive lung disease has classically required the
      measure of total lung capacity to document 'true' restriction, which has limited
      its detection in large population-based studies. METHODS: We used spirometric
      data to classify people with  restricted spirometry (forced expiratory volume in
      1 second [FEV(1)]/forced vital capacity >= 0.70 and FEV(1) < 80% predicted) in
      the Burden of Lung Disease (BOLD) Study and determined the relation between this
      finding and demographic factors and the presence of chronic  diseases, including
      diabetes mellitus, hypertension and cardiovascular disease. RESULTS: Overall, we
      found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted
      spirometry. Prevalence varied widely by site, from a low of 4.2% among males in
      Sydney, Australia, to a high  of 48.7% among females in Manila, The Philippines.
      Compared to people with normal lung function, those with restricted spirometry
      had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs.
      7.7%) and hypertension (38.8% vs. 22.8%). CONCLUSIONS: Restricted spirometry is 
      a common finding in population studies. Additional research is needed to better
      define and describe the mechanisms that lead to restricted spirometry and
      potential interventions.

PMID- 22863566
TI  - Dechloranes in a river in northeastern China: spatial trends in multi-matrices
      and bioaccumulation in fish (Enchelyopus elongatus).
AB  - Dechloranes (Decs), including Dechlorane Plus (DP) and Dechlorane (Dec) 602, 603,
      604, are used as flame retardants. Fifty four samples were collected in a river
      in northeastern China and analyzed for Decs by gas chromatography/mass
      spectrometry. The average concentrations of total DP (syn- and anti-) in water,
      sediment, air, reed (Phragmites australis), and fish (E. elongatus) were 0.30+/
      0.24 (mean+/-SD) ng L(-1), 1.3+/-0.69 ng g(-1) dry weight (dw), 0.25+/-0.18 ng m(
      3), 0.63+/-0.18 ng g(-1) wet weight (ww), and 29+/-20 ng g(-1) lipid weight (lw),
      respectively. While Dec 602 and Dec 603 were detected in most of sediment and
      fish samples, no Dec 604 was found in any of the investigated environmental
      matrices. The mean ratio of syn-DP to total DP (fsyn) in water, sediment, reed,
      and fish were 0.28, 0.25, 0.27 and 0.47, suggesting depletion in abiota and
      enrichment in biota for syn-DP. It was found that biota-sediment accumulation
      factor (BSAF) was 4.7 for Dec 602, 0.88 for syn-DP, and 0.33 for anti-DP.

PMID- 22863567
TI  - The CC1-FHA tandem as a central hub for controlling the dimerization and
      activation of kinesin-3 KIF1A.
AB  - Kinesin-3 KIF1A plays prominent roles in axonal transport and synaptogenesis.
      KIF1A adopts a monomeric form in vitro but acts as a processive dimer in vivo.
      The mechanism underlying the motor dimerization is poorly understood. Here, we
      find that the CC1-FHA tandem of KIF1A exists as a stable dimer. The structure of
      CC1-FHA reveals that the linker between CC1 and FHA unexpectedly forms a beta
      finger hairpin, which integrates CC1 with FHA assembling a CC1-FHA homodimer.
      More importantly, dissociation of the CC1-FHA dimer unleashes CC1 and the beta
      finger, which are both essential for the motor inhibition. Thus, dimerization of
      the CC1-FHA tandem not only promotes the KIF1A dimer formation but also may
      trigger the motor activity via sequestering the CC1/beta-finger region. The CC1
      FHA tandem likely functions as a hub for controlling the dimerization and
      activation of KIF1A, which may represent a new paradigm for the kinesin
      regulation shared by other kinesin-3 motors.

PMID- 22863568
TI  - Tetrameric interaction of the ectoenzyme CD38 on the cell surface enables its
      catalytic and raft-association activities.
AB  - The leukocyte cell-surface antigen CD38 is the major nicotinamide adenide
      dinucleotide glycohydrolase in mammals, and its ectoenzyme activity is involved
      in calcium mobilization. CD38 is also a raft-dependent signaling molecule. CD38
      forms a tetramer on the cell surface, but the structural basis and the functional
      significance of tetramerization have remained unexplored. We identified the
      interfaces contributing to the homophilic interaction of mouse CD38 by site
      specific crosslinking on the cell surface with an expanded genetic code, based on
      a crystallographic analysis. A combination of the three interfaces enables CD38
      to tetramerize: one interface involving the juxtamembrane alpha-helix is
      responsible for the formation of the core dimer, which is further dimerized via
      the other two interfaces. This dimerization of dimers is required for the
      catalytic activity and the localization of CD38 in membrane rafts. The
      glycosylation prevents further self-association of the tetramer. Accordingly, the
      tetrameric interaction underlies the multifaceted actions of CD38.

PMID- 22863570
TI  - Differential effects of mixed lymphocyte reaction supernatant on human
      mesenchymal stromal cells.
AB  - The concept that mesenchymal stromal cells (MSCs), a component of the
      hematopoietic microenvironment, can be a target for alloreactive effector cells
      in the context of graft-vs-host disease has not been investigated in detail.
      Mixed lymphocyte reaction (MLR) supernatant was used to mimic the inflammatory
      milieu induced by an allogeneic immune response in vitro. In addition to
      phenotype and proliferation, we monitored MSC differentiation, gene expression,
      and support of CD34(+) hematopoietic stem and progenitor cells after priming with
      MLR supernatant. Priming of MSCs with MLR supernatant led to an 11-fold decrease
      in cobblestone area-forming cells in the 4-week coculture (p < 0.05) and a
      threefold decrease of colony-forming unit macrophage in the colony-forming cell
      assay (p < 0.05). MSC proliferation over 8 days was increased 2.5-fold (p <
      0.05). Osteogenic differentiation was enhanced, while adipogenesis was
      concurrently suppressed. In addition, the surface expression of HLA-DR and
      intercellular adhesion molecule-1 was increased 20-fold (p = 0.06) and 45-fold (p
      < 0.05), respectively. This was associated with increased adhesion of
      hematopoietic stem and progenitor cells to MLR-treated MSCs. In summary, our data
      shed light on the dysfunction of the stromal environment during graft-vs-host
      disease, possibly aggravating cytopenia and leading to an enhanced immunogenicity
      of MSCs.

PMID- 22863569
TI  - ATP-driven remodeling of the linker domain in the dynein motor.
AB  - Dynein ATPases are the largest known cytoskeletal motors and perform critical
      functions in cells: carrying cargo along microtubules in the cytoplasm and
      powering flagellar beating. Dyneins are members of the AAA+ superfamily of ring
      shaped enzymes, but how they harness this architecture to produce movement is
      poorly understood. Here, we have used cryo-EM to determine 3D maps of native
      flagellar dynein-c and a cytoplasmic dynein motor domain in different nucleotide
      states. The structures show key sites of conformational change within the AAA+
      ring and a large rearrangement of the "linker" domain, involving a hinge near its
      middle. Analysis of a mutant in which the linker "undocks" from the ring
      indicates that linker remodeling requires energy that is supplied by interactions
      with the AAA+ modules. Fitting the dynein-c structures into flagellar tomograms
      suggests how this mechanism could drive sliding between microtubules, and also
      has implications for cytoplasmic cargo transport.

PMID- 22863571
TI  - Mild hyperhomocysteinemia alters extracellular adenine metabolism in rat brain.
AB  - Since homocysteine (Hcy) is considered a risk factor to cerebral diseases and
      adenine nucleotides are important molecules to brain normal function, in the
      present study we investigated the effect of chronic mild hyperhomocysteinemia on
      ectonucleotidase activities and expression in rat cerebral cortex. The levels of
      ATP, ADP, AMP and adenosine (Ado) in cerebrospinal fluid (CSF) of adult rats also
      were evaluated by high-performance liquid chromatography. For the chronic
      chemically induced mild hyperhomocysteinemia, Hcy (0.03 MUmol/g of body weight)
      was administered subcutaneously from the 30th to the 60th day of life. Control
      rats received saline solution in the same volumes. Results showed that Hcy
      significantly decreased nucleotide hydrolysis in the synaptosomal fraction and
      increased E-NTPDase1 and ecto-5'-nucleotidase transcripts in rat cerebral cortex.
      ATP levels were significantly increased, while Ado decreased in CSF of Hcy
      treated rats. These findings suggest that the unbalance in ATP and Ado levels may
      be, at last in part, involved in the cerebral toxicity of mild
      hyperhomocysteinemia.

PMID- 22863572
TI  - Long-term changes in reward-seeking following morphine withdrawal are associated
      with altered N-methyl-D-aspartate receptor 1 splice variants in the amygdala.
AB  - The NR1 subunit of the NMDA receptor can be alternatively spliced by the
      insertion or removal of the N1, C1, C2, or C2' regions. Morphine dependence and
      withdrawal were previously demonstrated to lower N1 and C2' in the accumbens and
      lower N1, C1, and C2' in the amygdala (AMY). Withdrawal has also been
      demonstrated to increase motivational and anxiety/stress behaviors in rats. We
      tested the hypothesis that NR1 splicing would be associated with these behaviors
      during an extended withdrawal period of 2 months. Motivation was measured using
      an operant orofacial assay at non-aversive temperatures (37 degrees C) while
      anxiety and stress were measured by examining this behavior at aversive
      temperatures (46 degrees C). Lower C1 and C2 expression levels were observed in
      the AMY in a subset of the population of withdrawn rats even after 2 months of
      morphine withdrawal. These subsets were associated with a hypersensitivity to
      adverse conditions which may reflect long-term alterations in the withdrawn
      population.

PMID- 22863573
TI  - Analysis of CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms in a population
      from South-Eastern Europe.
AB  - The CYP2C9 enzyme metabolizes a wide range of relevant drugs, among which are
      oral anticoagulants. VKORC1 is the pharmacodynamic target of the oral
      anticoagulants. The genetic polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A
      are the major determinants of the inter-individual variability in the dosage
      requirements of oral anticoagulants. This study provides a first evaluation of
      these 3 polymorphisms in a Romanian population. A total of 332 Romanian
      individuals were genotyped for the CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A
      polymorphisms using the PCR-RFLP technique. Sixty-two individuals (18.7%) were
      heterozygous for CYP2C9*2, whereas 47 individuals (14.1%) were heterozygous for
      CYP2C9*3. Fourteen individuals (4.2%) had a CYP2C9*2 homozygous, CYP2C9*3
      homozygous or CYP2C9*2/CYP2C9*3 compound heterozygous genotype. These individuals
      are predicted to have the lowest CYP2C9 enzymatic activity. The allele
      frequencies of the CYP2C9*2 and CYP2C9*3 polymorphisms were 11.3% and 9.3%
      respectively. For the VKORC1 -1639 G>A polymorphism, there were 170 heterozygotes
      (51.2%) and 55 (16.6%) homozygotes for the A allele. The frequency of the A
      allele was 42.2%. Overall, the distribution of the CYP2C9*2, CYP2C9*3 and VKORC1 
      1639 G>A polymorphisms observed in our cohort is in accordance with other
      Caucasian populations. A large number of Romanians are expected to harbour at
      least one CYP2C9 variant allele and/or one VKORC1 -1639 G>A allele. This
      frequency has major implications in the pharmacogenomics of oral anticoagulants
      in Romanians.

PMID- 22863574
TI  - Molecular mechanism of rifampicin and isoniazid resistance in Mycobacterium
      tuberculosis from Bangladesh.
AB  - Despite having 100% coverage of directly observed treatment short-course, multi
      drug-resistant (MDR) tuberculosis (TB) is still increasing in Bangladesh. Early
      detection of MDR-TB by rapid molecular test and early initiation of treatment
      will effectively stop this trend. To develop rapid diagnostic tools, molecular
      characterization of genes conferring Mycobacterium tuberculosis resistance to
      rifampicin (RIF) and isoniazid (INH) will be required. Hence, this study
      elucidated the molecular mechanism RIF and INH resistance in 218 MDR strains from
      hospitalized (n = 161) and non-hospitalized (n = 57) TB patients in Bangladesh.
      Mutations in rpoB gene were detected in 207 (95.0%) with majority at codon 531
      (52.3%). Mutations in katG or inhA or both were detected in 206 (94.5%) with
      majority at codon 315 of katG (83.9%). It was noteworthy that a novel C to T
      mutation at position -34 and G to A mutations at position -47 in inhA regulatory
      region were found, respectively, in combination with mutation at codon 315 of
      katG. This is the first comprehensive molecular analysis of rpoB and katG genes
      and inhA regulatory regions of MDR isolates from Bangladesh. This study provides
      basic data for the construction of low cost tailor-made molecular system for
      rapid diagnosis of MDR-TB in Bangladesh.

PMID- 22863575
TI  - The link between enthesitis and arthritis in psoriatic arthritis: a switch to a
      vascular phenotype at insertions may play a role in arthritis development.
AB  - OBJECTIVE: Subclinical enthesopathy is recognised in both psoriasis and psoriatic
      arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test
      the hypothesis that subclinical enthesopathy in PsA was associated with an
      'inflammatory' or vascular phenotype compared to that seen in psoriasis. METHODS:
      100 patients with a mean age of 46.3 years (SD 15) (42 with psoriasis and 58 with
      PsA) and 23 matched healthy controls (HC) from two centres were included. 1230
      lower limb entheses were scanned by ultrasonographers blinded to clinical
      details. Both inflammatory and chronic features of enthesopathy were scored.
      RESULTS: Psoriasis patients (with or without arthritis) were more likely to
      express a vascular phenotype, with higher inflammation-related enthesopathy
      scores than HC (for inflammation p<0.0001, for chronicity p=0.02, for total
      ultrasound scores p<0.0001). The PsA patients had higher ultrasound enthesopathy
      scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC
      (inflammation p<0.0001, chronicity p=0.003). When symptomatic entheses were
      excluded, PsA patients still had higher PD scores than psoriasis patients
      (p=0.003). Doppler positivity in at least one entheseal site was observed more
      frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002).
      CONCLUSIONS: This study shows that the ultrasound appearances of subclinical
      enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA
      patients having more PD. This is suggestive of a more inflammatory or vascular
      process in PsA, and offers potentially novel insights into the progression from
      skin to joint disease in psoriasis.

PMID- 22863576
TI  - NSAIDs and radiographic progression in ankylosing spondylitis Bagging big game
      with small arms?

PMID- 22863577
TI  - Gout: why is this curable disease so seldom cured?
AB  - Gout is the most common inflammatory arthritis and one in which pathogenesis and
      risk factors are best understood. One of the treatment objectives in current
      guidelines is 'cure'. However, audits show that only a minority of patients with
      gout receive adequate advice and treatment. Suboptimal care and outcomes reflect
      inappropriately negative perceptions of the disease, both in patients and
      providers. Historically, gout has been portrayed as a benign and even comical
      condition that is self-inflicted through overeating and alcohol excess. Doctors
      often focus on managing acute attacks rather than viewing gout as a chronic
      progressive crystal deposition disease. Urate-lowering treatment is
      underprescribed and often underdosed. Appropriate education of patients and
      doctors, catalysed by recent introduction of new urate-lowering treatments after
      many years with no drug development in the field, may help to overcome these
      barriers and improve management of this easily diagnosed and curable form of
      potentially severe arthritis.

PMID- 22863578
TI  - Removal of phenol from synthetic waste water using Gemini micellar-enhanced
      ultrafiltration (GMEUF).
AB  - Comprehensive studies were conducted on the phenol wastewater ultrafiltration
      (UF) with the help of various concentrations of cationic Gemini surfactant (N1
      dodecyl-N1,N1,N2,N2-tetramethyl-N2-octylethane-1,2-diaminium bromide, CG),
      conventional cationic surfactant (dodecyl trimethyl ammonium bromide, DTAB),
      anionic surfactant (sodium dodecyl sulfate, SDS) and nonionic surfactant
      ((dodecyloxy)polyethoxyethanol, Brij35). A flat sheet module with
      polyethersulfone (PES) membrane was employed in this investigation. The effects
      of feed concentration (phenol and surfactant) on the retention of phenol and
      surfactant, permeate flux and membrane fouling by micelles were evaluated. The
      distribution coefficient (D), the loading of the micelles (L(m)) and the
      equilibrium distribution constant (K) were also utilized to estimate the micellar
      enhanced ultrafiltration ability for phenol. Scanning electron microscope (SEM),
      Fourier transform infrared spectrometer with attenuated total reflectance
      accessory (ATR-FTIR) and mercury porosimeter were applied to analyze membrane
      surface morphology, membrane material characteristics and membrane fouling for
      the original and fouled membranes. Based on the above analysis, the performance
      of the selected Gemini surfactant was proved superior in the following aspects:
      retention of phenol/surfactant (peak value is 95.8% for phenol retention),
      permeate flux and membrane fouling with respect to other conventional surfactants
      possessing equal alkyl chain length. These results demonstrated that CG
      surfactant with exceptional structure has favorable prospects in the treatment of
      phenol wastewater by the micellar-enhanced ultrafiltration.

PMID- 22863579
TI  - [Release of HMGB1 by LPS-treated cardiac fibroblasts and its contribution to the
      production of collagen type  I   and    III].
AB  - AIM: To investigate whether cardiac fibroblasts (CFs) treated by LPS can actively
      secrete high-mobility group box protein 1 (HMGB1) and to analyze the correlation
      between HMGB1 releasing and the accumulation of collagen type  I ,  III .
      METHODS: CFs were isolated from the heart of 7-14-day-old BALB/c mice and
      cultured in DMEM with 10% fetal bovine serum (FBS). We collected the CFs and cell
      supernatants after treated by LPS for 0, 6, 12, 24, 36, 48 h, respectively. The
      mRNA and protein expression levels of HMGB1, collagen 1a1 (col1a1) and collagen
      3a1 (col3a1) in CFs after LPS stimulation were detected by RT-PCR and Western
      blotting, respectively. The intracellular localization of HMGB1 in treated CFs
      was investigated by immunofluorescence. RESULTS: After 0-6 h of LPS stimulation,
      the mRNA levels of HMGB1, col1a1, col3a1 had no significant changes; but
      increased obviously at 12, 24, 36, 48 h. HMGB1 was found in the cell supernatant
      by Western blotting after 24  h LPS stimulation, and its expression decreased
      following the first rise in CFs. Meanwhile, immunofluorescence showed HMGB1
      translocation from nucleus to cytoplasm. The levels of col1a1 and col3a1 were up
      regulated in CFs after stimulation. CONCLUSION: LPS can induce HMGB1
      translocation from nucleus to cytoplasm and across cellular membrane to the
      outside of CFs at a time-dependent manner. Col1a1 and Col3a1, which are closely
      associated with myocardial fibrosis, were obviously up-regulated by LPS
      stimulation, which indicates that actively released HMGB1 might contribute to
      myocardial fibrosis following the endotoxin induced-sepsis.

PMID- 22863580
TI  - [Role of let-7 in maintaining characteristics of breast cancer stem cells].
AB  - AIM: To observe the expression of let-7 in breast cancer stem cells and explore
      the role of let-7 in maintaining the characteristics of breast cancer stem cells.
      METHODS: We separated breast cancer stem cells (SP and NSP) from MCF-7 cell line
      using SP sorting, and observed the expression of let-7a/b/c on SP and NSP cells
      using quantitative real-time PCR and the expressions of Ras and ERK using Western
      blotting to study the mechanism by which let-7 maintains the characteristics of
      breast cancer stem cells. RESULTS: The SP cells accounted for 3.3% in MCF-7
      cells, however, the rate dropped to 0.4% when verapamil was added into the
      process of seperation. The level of Let-7a/b/c in SP cells were lower than that
      in NSP cells, and among let-7 miRNAs, let-7b/c showed the most obvious
      difference. The expressions of t-Ras and t-ERK showed no difference between SP
      and NSP cells, nevertheless, the expressions of p-Ras, p-ERK were higher in SP
      cells than in NSP cells. CONCLUSION: SP sorting is an effective method to
      separate cancer stem cells. There do exist cancer stem cells in MCF-7 breast
      cancer cell line. Let-7 is down-regulated in SP cells, and the down-regulation
      makes let-7 lose the opportunity to restrain Ras mRNA, finally, p-Ras and p-ERK
      are activated. They play an important role in maintaining the characteristics of
      breast cancer stem cells.

PMID- 22863582
TI  - [Construction, expression and immunogenicity of EV71 multiepitope-mGITRL
      eukaryotic plasmid].
AB  - AIM: To construct an enterovirus 71(EV71) multiepitope-mGITRL eukaryotic plasmid
      and study its immunogenicity in BALB/c mice. METHODS: We first designed and
      synthesized VP1' epigene containing two B cells and two T cells epitopes of VP1,
      and amplified mGITRL gene by PCR. The VP1' epigene and mGITRL gene were then
      cloned into the expression vector pIRES to construct the recombination plasmid
      pIRES-VP1'-mGITRL. The recombination plasmid was transfected into COS7 cells by
      liposome-mediated method. The protein expressions of VP1' and mGITRL were
      detected by Western blotting. BALB/c mice were immunized with pIRES-VP1'-mGITRL
      plasmid, and its serum antibody titer was measured by ELISA. RESULTS: The
      recombination plasmid pIRES-VP1'-mGITRL was successfully constructed as
      demonstrated by sequencing. Western blot analysis indicated that the VP1'-mGITRL
      fusion protein was expressed in COS7 cells and muscle cells. After BALB/c mice
      were immunized with this plasmid, we detected the high titer of anti-VP1 antibody
      in serum. CONCLUSION: VP1'-mGITRL fusion protein can be highly expressed in COS7
      cells and muscle cells by the construction and transfection of the recombination
      plasmid pIRES-VP1'-mGITRL, and it could elicit the dramatic immune response in
      mice.

PMID- 22863581
TI  - [Notch pathway gene expression after co-culture of umbilical cord mesenchymal
      stem cells and hematopoietic stem cells].
AB  - AIM: To detect the gene expression of signal molecules involved in the Notch
      pathway after co-culture of umbilical cord mesenchymal stem cells (UC-MSCs) and
      CD34(+); hematopoietic stem cells. METHODS: UC-MSCs were isolated by collagenase
      digestion,  and the phenotype was tested by flow cytometry. The differentiation
      ability of UC-MSCs into adipocytes,  osteoblasts and chondroblasts was analyzed
      using three induction systems,  respectively. After UC-MSCs were co-cultured in
      vitro with CD34(+); cells for 6 d,  real-time PCR was applied to investigate the
      gene expressions of notch ligands (Jagged 1,  2 Delta1,  3,  4),  receptors
      (Notch1-4) and Hes-1. RESULTS: The isolated UC-MSCs were found with the typical
      characteristics of MSCs in morphology,  phenotype and differentiation ability.
      After  co-culture  in vitro of MSCs and CD34(+); cells,  real-time PCR assay
      showed a significant up-regulation of Jagged-1 and Notch1. The expression of Hes
      1 in CD34(+); cells also  increased,  but there was no obvious change after DAPT
      (50 nmol/L) was added in co-culture medium. CONCLUSION: Notch signaling may play
      an important role in the process of the expansion of hematopoietic stem cells
      supported by UC-MSCs.

PMID- 22863583
TI  - [Expression and potential role of metastasis-associated protein 1 in the induced
      carcinogenesis of mouse liver].
AB  - AIM: To establish a hepatocellular carcinoma model of BALB/c mouse and to study
      the expression and potential role of metastasis-associated protein 1 (MTA1) in
      the carcinogenesis process. METHODS: Normal adult male BALB/c mice were induced
      by the combined dimethylnitrosamine (DEN)/carbon tetrachloride (CCl(4);)/alcohol
      for 150 d. The  morphological changes in liver cells and the expression of MTA1
      in the liver lesions were observed by HE and immunohistochemical stainings,
      respectively. RESULTS: The pathological changes of the survivals'  livers in
      experimental group were liver inflammation, fibrosis and cancer in sequence. The
      level of MTA1 increased in the carcinogenesis process, and MTA1 was mainly
      expressed in the cytoplasm of the cells suffering cirrhosis. CONCLUSION: The
      changes of the expression sites and quantity of MTA1 in the DEN-induced
      carcinogenesis of mouse liver indicate that MTA1 may play an important role in
      the whole process of liver carcinogenesis.

PMID- 22863584
TI  - [Screening and identification of Polo-like kinase 1 as a 14-3-3Zeta-interacting
      protein].
AB  - AIM: To screen 14-3-3Zeta-interacting proteins by the yeast two-hybrid system and
      confirm the interaction between 14-3-3Zeta and Polo-like kinase 1 (Plk1).
      METHODS: A bait vector pGBKT7-14-3-3Zeta was constructed to screen the 14-3-3Zeta
      interacting proteins from the HeLa cDNA library by yeast two-hybrid system. The
      interaction between 14-3-3Zeta and Plk1 was further confirmed by
      immunoprecipitation assay. We also examined the distribution of endogenous 14-3
      3Zeta and Plk1 in mitosis using immunofluorescent staining. RESULTS: Plk1 was
      identified as a partner of 14-3-3Zeta protein by the yeast two-hybrid system.
      Immunoprecipitation assay demonstrated the interaction between 14-3-3Zeta and
      Plk1. Immunofluorescence indicated 14-3-3Zeta was colocalized with Plk1 at the
      midbody during cytokinesis. CONCLUSION: Plk1 is a serine/threonine protein kinase
      that plays multiple critical roles in centrosome maturation, mitotic chromosome
      segregation, cytokinesis, and the DNA damage response. The interaction between 14
      3-3Zeta and Plk1 suggests 14-3-3 family emerges as a novel player in the mitotic
      regulation.

PMID- 22863585
TI  - [Influence of angiotensin-(1-7) on cell activation in rat renal interstitial
      fibroblasts induced by aldosterone].
AB  - AIM: To explore the influence of angiotensin-(1-7) [Ang-(1-7)] on cell 
      activation and extracellular matrix secretion in rat renal interstitial
      fibroblasts (NRK-49F) induced by aldosterone (ALD). METHODS: The NRK-49F cells
      were cultured in vitro, and then were divided into control group, ALD group, Ang
      (1-7) group, and ALD+Ang-(1-7) group. When the cells were cultured for 48 h, the
      expression of alpha-smooth muscle actin (alpha-SMA) (a sign of cell activation)
      was detected by immunocytochemistry; the level of collagen type  I (Col I ) in
      the cultured supernatant was measured by enzyme-linked immunosorbent assay
      (ELISA). When the cells were cultured for 30 min, the expressions of
      phosphorylated and total ERK1/2 (pERK1/2, tERK1/2) in the cell lysate were
      detected by Western blotting. RESULTS: Compared with control group, the
      expressions of alpha-SMA, Col I  and the Phos/Total ERK1/2 ratio in ALD group and
      ALD+Ang-(1-7) group increased significantly (P<0.05). Compared with ALD group,
      the expressions of alpha-SMA, Col I  and the Phos/Total ERK1/2 ratio in ALD+Ang
      (1-7) group decreased significantly (P<0.05). CONCLUSION: Ang-(1-7) can inhibit
      ALD-induced cell activation and decrease the secretion of Col I  in rat renal
      interstitial fibroblasts. Inhibition of ERK1/2 pathway may play an important role
      in this process.

PMID- 22863586
TI  - [Mass spectrometry identification and immune cross-reactivity of a minor shrimp
      allergen-sarcoplasmic calcium binding protein from Litopenaeus vannamei].
AB  - AIM: To identify sarcoplasmic calcium-binding protein (SCP) as a minor shrimp
      allergen by mass spectrometry, and to analyze the immune cross-reactivity among
      crustacean SCPs. METHODS: The M(r); 21 000 allergen from Litopenaeus vannamei was
      identified by MALDI-TOF/TOF-MS. BLAST and ClustalW were used to compare amino
      acid sequence identity of the allergen among crustaceans. The puritifed M(r); 21
      000 allergen was injected subcutaneously in mice to produce the specific
      polyclonal antibodies to analyze immune cross-reactivity of the allergen with
      proteins from 8 other species of crustaceans by Western blotting. RESULTS: The
      M(r); 21 000 shrimp allergen was identified as SCP. Sequence comparison revealed
      that SCP had 81%-100% amino acid identity among crustaceans. Western blotting
      showed that the proteins with M(r); about  21 000, corresponding to SCP from
      Metapenaeus ensis, Penaeus monodon, Oratosquilla oratoria, Macrobrachium
      rosenbergii, Procambarus clarkii, Portunus pelagicus, Charybdis feriatus,
      Eriocheir sinensis were recognized by polyclonal antibodies against SCP of
      Litopenaeus vannamei. CONCLUSION: SCP is a minor shrimp allergen, and SCPs have a
      high sequence homology and strong immune cross-reactivity among crustaceans,
      which can be used as detective, diagnostic and safe immunotherapeutic agents for
      subjects with shrimp allergy.

PMID- 22863587
TI  - [Splicing factor SC35 regulated the expression of B7-H3 in vitro].
AB  - AIM: To explore the mechanisms by which splicing factor SC35 regulates the
      costimulatory molecule B7-H3 expression in vitro through bioinformatic and
      molecular  biological methods. METHODS: We screened some regulatory proteins
      which might take part in regulating B7-H3 expression using bioinformatic methods.
      Then RNA interference (RNAi) and real-time PCR were performed to test if these
      proteins took part in the regulation. RESULTS: Splicing factor SC35, SRP40 and
      SF50 might play an important role in the regulation of B7-H3 expression. In PHA
      activated T cells, B7-H3 was upregulated obviously and at the same time SC35 was
      also upregulated. When we suppressed SC35 expression using RNAi, we found B7-H3
      was also downregulated. CONCLUSION: Splicing factor SC35 might take part in the
      regulation of B7-H3 expression, which could help understand B7-H3 biological
      function.

PMID- 22863588
TI  - [Effect of Fasudil on the phenotype conversion of LPS-stimulated BV-2 microglia].
AB  - AIM: To explore the effect of Fasudil on LPS-stimulated BV-2 microglia in
      inflammatory reaction and phenotype conversion. METHODS: The routinely cultured
      BV-2 microglia in vitro were divided into PBS control group, PBS plus Fasudil
      treatment group, LPS stimulation group and LPS plus Fasudil group. We determined
      the production of NO by Griess reaction, the level of TNF-alpha  by ELISA, and
      analyzed the M1 and M2 phenotypes of microglia by flow cytometry. RESULTS: The
      treatment of LPS lead to the characteristics of M1 phenotype in BV-2 microglia.
      Fasudil inhibited the production of NO and the release of TNF-alpha  in LPS
      stimulated BV-2 microglia. Interestingly, Fasudil transformed inflammatory M1
      cells to anti-inflammatory M2 cells. CONCLUSION: Fasudil shows an anti
      inflammatory effect, which may be associated with the conversion of inflammatory
      M1 microglia to anti-inflammatory M2 cells.

PMID- 22863589
TI  - [Amplification of  gammadelta T cells in PBMCs of healthy donors and osteosarcoma
      patients stimulated by zoledronate].
AB  - AIM: To investigate the amplification and cytotoxicity of gammadelta T cells in
      peripheral blood mononuclear cells (PBMCs) of healthy donors and osteosarcoma
      patients stimulated by zoledronate (Zol) and IL-2. METHODS: PBMCs from healthy
      donors and osteosarcoma patients were stimulated with IL-2 and Zol+IL-2, 
      respectively. After 14-day culture,  the purity of gammadelta T cells was
      assessed by flow cytometry.  The cytotoxicity of gammadelta T cells against
      target cells was analyzed using a standard lactate dehydrogenase release assay
      with gammadelta T lymphocyte-sensitive Daudi cells,  gammadelta T lymphocyte
      resistant Raji cells and human osteoblast cell line,  hFOB,  as the target cells.
      RESULTS: After 2-week culture ex vivo of PBMCs from healthy donors and
      osteosarcoma patients,  compared with stimulation of IL-2,  Zol+IL-2
      significantly promoted the amplification of gammadelta T cells. In addition, 
      gammadelta T cells showed the higher cytotoxicity against Daudi cells,  but no
      cytotoxic effect on normal cells like hFOB. CONCLUSION: gammadelta T cells of
      high purity and high cytotoxicity can be obtained by the stimulation of Zol
      combined with IL-2 on PBMCs from healthy donors and osteosarcoma patients.

PMID- 22863590
TI  - [Purification of recombinant AKR7A5 protein and measurement of substrate
      specificity of AKR7A5 towards naphthoquinone and its derivatives].
AB  - AIM: To investigate the substrate specificity of mouse aldo-keto reductase AKR7A5
      protein towards naphthoquinone and its derivatives. METHODS: The recombinant His
      tagged AKR7A5 fusion protein in E.coli BL21pLysS cell strain was induced by IPTG
      and purified using FPLC system through HiTrap affinity column. The purified
      recombinant AKR7A5 protein was confirmed by SDS-PAGE and Western blotting. AKR
      enzyme assay was applied to measure the substrate specificity of recombinant
      AKR7A5 protein towards naphthoquinone and its derivatives. RESULTS: Recombinant
      His-AKR7A5 was successfully purified as confirmed by SDS-PAGE and Western
      blotting. AKR enzyme assay indicated that the recombinant AKR7A5 protein
      exhibited mild substrate specificity towards lawsone and low specificity towards
      juglone and vitamine K3,  but no activity towards 1, 4-naphthoquinone.
      CONCLUSION: AKR7A5 has selective substrate specificity towards naphthoquinone
      derivatives,  suggesting that the aldo-keto reductase could play an important
      role in metabolism of certain naphthoquinone derivatives.

PMID- 22863591
TI  - [Isolation and identification of single chain Fv antibodies against breast cancer
      from a human phage display library].
AB  - AIM: To isolate and identify single chain Fv (scFv) antibodies against breast
      cancer from a constructed human phage display library. METHODS: Recombinant
      phages specific for breast cancer cells were enriched after four-round screening
      with MCF-7 cells. We selected the antigen-positive ones from the enriched clones
      by phage ELISA. The positive clones were used to infect E.coli HB2151 to express
      soluble scFv antibody. The antigen binding activity of the soluble antibodies was
      detected by Western blotting. RESULTS: The specific antibodies against MCF-7
      cells were enriched after four rounds of affinity selection. SDS-PAGE and Western
      blotting showed a band at relative molecular mass 30 000 Da, which indicated
      soluble antibodies were present. ELISA analysis revealed that soluble antibodies
      had the affinity to a human breast cancer cell line MCF-7 but not to other cancer
      cell line, which demonstrated scFv could react specifically with breast cancer
      cells. CONCLUSION: We constructed a scFv phage library against human breast
      cancer with high capacity by phage display technology. The scfv was demonstrated
      successfully to be expressed in E.coli HB215 and have a specificity to breast
      cancer. Our findings may provide an alternative approach, and a basis for further
      studies on diagnosis and therapy of breast cancer.

PMID- 22863592
TI  - [Preparation and identification of monoclonal antibodies against recombinant N
      protein of mouse hepatitis virus].
AB  - AIM: To prepare and characterize the monoclonal antibodies (mAbs) against N
      protein of mouse hepatitis virus (MHV). METHODS: BALB/c mice were
      immunostimulated with the purified recombinant N protein expressed by Bac-to-Bac
      baculovirus expression system. Then the spleen cells of the immunized mice were
      fused with Sp2/0 myeloma cells by conventional hybridoma techniques. An indirect
      ELISA using recombinant N protein as antigen was established to screen antibody
      producing hybridoma cell lines. Western blotting and IFA were applied to
      characterize the mAbs. RESULTS: We obtained four hybridoma cell lines secreting
      mAbs against recombinant N protein. The subclasses of two mAbs were IgG2a,  one
      IgG2b and the other IgG1,  and light chains were both Kappa. Western blotting
      showed that the mAbs specifically recognized certain antigenic epitope of N
      protein of MHV. CONCLUSION: mAbs against N protein of MHV with high activity and
      specificity were prepared successfully,  which provides a potential basis for
      further researches on N protein function and diagnostic methods.

PMID- 22863593
TI  - [Prokaryotic expression of Drosophila selenoprotein D-SelK and preparation of
      polyclonal antibody to D-SelK].
AB  - AIM: To clone and encode Drosophila selenoprotein D-SelK structure gene, express
      it in E.coli efficiently, and after purification, to generate its antibody in
      rabbits. METHODS: D-SelK gene segment amplified from pGM-T-D-SelK plasmid by PCR
      was inserted into pGEX-6p-1 to construct recombinant plasmid pGEX-6p-1-D-SelK.
      The recombinant plasmid was transfected into E.coli BL21(DE3) to express the
      recombinant protein D-SelK in E.coli under IPTG induction. The protein was
      purified by denaturation and electrophoresis, and then identified by SDS-PAGE and
      Western blotting. Polyclonal antibody to D-SelK was obtained by immunizing
      rabbits with the protein. Quality and quantity of the antibody was examined.
      RESULTS: D-SelK gene segment was successfully inserted into pGEX-6p-1 and the
      positive clones of the recombinant plasmid was identified by PCR screening and
      restriction endonuclease analysis. The target protein was effectively expressed
      in E.coli by the IPTG induction. Through immunizing rabbits with the purified
      target protein, we obtained the specific antibodies to D-SelK, the titer of which
      was more than 1:51 200. The polyclonal antibody had a good specificity to D-SelK.
      CONCLUSION: D-SelK recombinant protein and rabbit anti-D-SelK polyclonal antibody
      with high specificity were obtained, which provides good tools for further
      research on the functional characterization of D-SelK.

PMID- 22863594
TI  - [Preparation of anti-BRDT-NY polyclonal antibody and expression of BRDT-NY
      protein in digestive tract tumors].
AB  - AIM: To prepare the mouse polyclonal antibody against human BRDT-NY prokaryotic
      protein and analyze the expression of BRDT-NY protein in digestive tract tumors.
      METHODS: The N-terminal amino acids of BRDT-NY protein was amplified by PCR and
      cloned into the expression vector pET28a(+). The recombinant plasmid pET28a+-BRDT
      NY was transformed into E.coli BL21 and induced to express the recombinant
      protein with IPTG. We immunized BALB/c mice with the purified BRDT-NY protein for
      preparing the specific polyclonal antibody. The titer of the antibody was
      analyzed by ELISA. The expression of BRDT-NY protein in digestive tract tumors
      was detected by immunohistochemistry. RESULTS: Recombinant human BRDT-NY protein
      was expressed in BL21 and purified successfully by Ni-affinity chromatography.
      Two months after the mice were immunized with the purified BRDT-NY protein, we
      obtained the specific polyclonal antibody of high titer 1:100 000.
      Immunohistochemical analysis revealed that BRDT-NY protein was highly expressed
      in digestive tract tumors. CONCLUSION: The successful preparation of mouse
      polyclonal antibody against BRDT-NY lays a foundation for the research on the
      role of BRDT-NY protein in the pathology of human digestive tract tumors.

PMID- 22863595
TI  - [Expression of oxidative stress proteins in the clear-cell renal cell carcinoma].
AB  - AIM: To investigate the expression of the oxidative stress proteins in human
      clear-cell renal cell carcinoma (CRCC) cell line (RLC-310) and normal renal
      proximal tubule epithelial cell line (HK-2),  the CRCC and the corresponding
      normal renal tissues. METHODS: RLC-310 and HK-2 cells were cultured in vitro.
      Total proteins of the two cell lines were separated by PF-2D protein
      fractionation system. The differentially expressed proteins of the two cell lines
      were analyzed using capillary LC-ESI-MS/MS and identified using the protein
      database. The representative differential oxidative stress proteins were verified
      by immunohistochemistry in the CRCC and corresponding normal renal tissues.
      RESULTS: Twelve differentially expressed oxidative stress proteins were
      identified,  including peroxiredoxin-1,  peroxiredoxin-6 (PRX-6),  superoxide
      dismutase[Cu-Zn] SOD1,  catalase,  glutathione peroxidase 1,  glutathione
      synthetase,  glutathione S-transferase Pi (GSTPi),  thioredoxin,  heat shock
      protein 10 (HSP10),  HSP60,  HSP70 and HSP90. Three representative differential
      proteins PRX-6,  HSP60 and GSTPi were both expressed in RLC-310 and HK-2,  and
      the levels of these proteins were significantly higher in RLC-310 than those in
      HK-2 (P<0.05). The levels of these proteins were significantly higher in CRCC
      than those in corresponding normal renal tissues (P<0.05). CONCLUSION: A series
      of oxidative stress proteins are overexpressed in the CRCC. They play an
      important role in preventing oxidative damage of CRCC cells.

PMID- 22863596
TI  - [Expression of B7-H3 costimulatory molecule in peripheral blood of myasthenia
      gravis patients].
AB  - AIM: To reveal the clinical significance of B7-H3 costimulatory molecule in
      myasthenia gravis (MG) patients by analyzing membranous B7-H3 (mB7-H3) and
      soluble B7-H3 (sB7-H3) expressions. METHODS: We collected peripheral blood
      samples of 35 MG patients and 44 health controls (HC) and detected the expression
      of mB7-H3 on peripheral blood mononuclear cells (PBMCs) using flow cytometry.
      ELISA was performed to analyze the levels of sB7-H3 in plasma samples from MG
      patients and HC. RESULTS: There was no significant difference in the expressions
      of mB7-H3 on T lymphocytes, monocytes or B cells between MG patients and HC.
      However, the level of sB7-H3 from MG patients was (2.166+/-0.958) ng/mL,
      significantly lower than that from HC (3.379+/-0.768) ng/mL. The level of sB7-H3
      in general MG  (GMG) patients (1.664+/-0.699) ng/mL was lower than that in ocular
      MG (OMG) patients (2.396+/-0.985) ng/mL. In MG patients complicated with abnormal
      thymus, the level of sB7-H3 was (1.593+/-0.441) ng/mL, also lower than that in MG
      patients with normal thymus (2.364+/-1.014) ng/mL. In addition, a significant
      negative correlation was found between the levels of sB7-H3 and QMGS in MG
      patients (r=-0.4189, P=0.012), but sB7-H3 was not associated with mB7-H3 in MG
      patients. CONCLUSION: In MG patients, down-regulation of sB7-H3 is finely
      correlated to the severity of the disease. Its different expression levels in
      various types of MG patients indicate that this costimulatory molecule may be
      involved in the immunopathogenesis of MG.

PMID- 22863597
TI  - [Receptor-ligand analysis of killer cell Ig-like receptor in Jiangsu Han
      population].
AB  - AIM: To investigate the distribution of killer cell immunoglobulin-like receptor
      (KIR) and its specific ligand human leukocyte antigen (HLA) in Jiangsu Han
      population. METHODS: 173 samples from unrelated healthy individuals of Jiangsu
      Han population were genotyped and observed for KIR,  HLA-Cw and HLA-Bw4 using a
      SYBR Green I real-time PCR and PCR-SSP method,  respectively. The number and type
      of KIR/HLA pairs inherited in each individual were analyzed. RESULTS: In Jiangsu
      Han population,  all four inhibitory KIR (2DL1,  2DL2/3,  3DL1 and 3DL2) that
      recognize the classical HLA class I molecules HLA-A,  -B and -C were present in
      >92% of the study group. Frequencies of 2DL2/HLA-C1,  2DL3/HLA-C1,  2DL1/HLA-C2
      and 3DL1/Bw4 were 0.243,  0.971,  0.457 and 0.590,  respectively;  frequencies of
      2DS1/HLA-C2 and 2DS2/HLA-C1 were 0.162 and 0.231,  respectively. 54.3% of the
      cases expressed KIR2DL1 without HLA-C1,  32.9% inherited 3DL1 without HLA-Bw4 and
      5.8% expressed HLA-Bw4 without 3DL1. 27.7% of the individuals had three iKIR/HLA
      pairs,  26% carried two iKIR/HLA pairs,  and 25.4% inherited a single iKIR/HLA
      pair and no one was deficient in all three iKIR/HLA pairs. CONCLUSION: There was
      disparity between KIR receptor and HLA ligand in Jiangsu Han population.
      Inhibitory KIR/HLA pair frequency was higher than stimulatory one. About 1/4 of
      the study group expressed a single iKIR/HLA pair alone.

PMID- 22863598
TI  - [Establishment of BA-ELISA method for detecting CEA in human  sera].
AB  - AIM: To establish a sensitive biotin-avidin enzyme linked immunosorbent assay (BA
      ELISA) method for detecting carcinoembryonic antigen (CEA) in serum. METHODS: CEA
      which had been purified by affinity chromatography was used to immunize the
      rabbits to produce polyclonal antibodies. Then the antibodies were connected with
      biotin and horseradish peroxidase (HRP). So BA-ELISA method was established on
      the basis of 96 microwell plates coated with biotinylated BSA. Finally we
      examined the sensitivity, specificity, stability and recovery rate of this system
      and compared the BA-ELISA method with the traditional ELISA, radioimmunoassay and
      chemiluminescence in detecting CEA concentrations. RESULTS: The stability of this
      system was proved good. The linear range was from 0.42 to 50 U/mL, the
      sensitivity was 0.42 U/mL, and the intra-differences together with inter
      differences were less than 10.0%. There was significant difference between BA
      ELISA and traditional ELISA, while there was no significant difference between BA
      ELISA and radioimmunoassay. The regression equation of this method was
      y=0.04825+0.99674x  and r=0.994, and there was no significant difference between
      the BA-ELISA and chemiluminescence. CONCLUSION: The BA-ELISA method we
      established to detect CEA was easy to operate, highly sensitive, low in price and
      suitable for application in clinical detection.

PMID- 22863599
TI  - Dopamine D2-agonist rotigotine effects on cortical excitability and central
      cholinergic transmission in Alzheimer's disease patients.
AB  - Dopamine is a neurotransmitter involved in several brain functions ranging from
      emotions control, movement organization to memory formation. It is also involved
      in the regulation of mechanisms of synaptic plasticity. However, its role in
      Alzheimer's disease (AD) pathogenesis is still puzzling. Several recent line of
      research instead indicates a clear role for dopamine in both amyloid beta
      formation as well as in cognitive decline progression. In particular it has been
      shown that dopamine D2-like receptors (namely D3 and D2) could be mostly
      responsible for dopamine dysfunction in AD. Here we aimed to study the effects of
      the dopamine agonist Rotigotine on cortical excitability and on central
      cholinergic transmission in cases of AD. Rotigotine is a dopamine agonist with a
      pharmacological profile with high affinity for D3 and D2 receptors. We used
      paired pulse protocols assessing short intracortical inhibition (SICI) and
      intracortical facilitation (ICF) to asses cortical excitability over the primary
      motor cortex and Short Latency Afferent Inhibition (SLAI) protocols, to verify
      the effects of the drug on central cholinergic transmission in a group of AD
      patients compared to age-matched controls. We observed that rotigotine induces
      unexpected changes in both cortical excitability (increased) and central
      cholinergic transmission (restored) of AD patients. These unexpected effects
      might depend on the dopamine D2-like receptors dysfunction previously described
      in AD brains. The current findings could indicate that future strategies aimed to
      ameliorate symptoms of the related AD cognitive decline could also involve some
      dopaminergic drugs. This article is part of a Special Issue entitled 'Cognitive
      Enhancers'.

PMID- 22863600
TI  - Nano- and microstructuring of graphene using UV-NIL.
AB  - In this work we demonstrate for the first time the micro- and nanostructuring of
      graphene by means of UV-nanoimprint lithography. Exfoliated graphene on SiO(2)
      substrates, as well as graphene deposited by chemical vapor deposition (CVD) on
      polycrystalline nickel and copper, and transferred CVD graphene on dielectric
      substrates, were used to demonstrate that our technique is suitable for large
      area patterning (2 * 2 cm(2)) of graphene on various types of substrates. The
      demonstrated fabrication procedure of micrometer as well as nanometer-sized
      graphene structures with feature sizes down to 20 nm by a wafer-scale process
      opens up an avenue for the low-cost and high-throughput manufacturing of graphene
      based optical and electronic applications. The processed graphene films show
      electron mobilities of up to 4.6 * 10(3) cm(2) V (-1) s(-1), which confirms them
      to exhibit state-of-the-art electronic quality with respect to the current
      literature.

PMID- 22863601
TI  - Training for efficiency: work, time, and systems-based practice in medical
      residency.
AB  - Medical residency is a period of intense socialization with a heavy workload.
      Previous sociological studies have identified efficiency as a practical skill
      necessary for success. However, many contextual features of the training
      environment have undergone dramatic change since these studies were conducted.
      What are the consequences of these changes for the socialization of residents to
      time management and the development of a professional identity? Based on
      observations of and interviews with internal medicine residents at three training
      programs, we find that efficiency is both a social norm and strategy that
      residents employ to manage a workload for which the demand for work exceeds the
      supply of time available to accomplish it. We found that residents struggle to be
      efficient in the face of seemingly intractable "systems" problems. Residents work
      around these problems, and in doing so develop a tolerance for organizational
      vulnerabilities.

PMID- 22863602
TI  - Effect of smoking on the functional aspects of sperm and seminal plasma protein
      profiles in patients with varicocele.
AB  - STUDY QUESTION: What are the effects of smoking on the functional aspects of the
      sperm, the levels of lipid peroxidation and the protein profile of seminal plasma
      in patients with varicocele? SUMMARY ANSWER: In men with varicocele, smoking is
      associated with altered semen quality, decreased sperm functional integrity and
      seminal oxidative stress. Alterations in seminal plasma protein profiles are also
      present and may explain the altered semen phenotype. WHAT IS KNOWN ALREADY:
      Varicocele is a major cause of male infertility. It reduces testicular blood
      renewal with a consequent accumulation of toxic substances. Thus, it can
      potentiate the toxic effects of environmental exposure to genotoxic substances
      such as those found in cigarette smoke. STUDY DESIGN, SIZE AND DURATION: A cross
      sectional study was performed in 110 patients presenting with variococele to the
      Human Reproduction Section of the Sao Paulo Federal University (2006-2010). The
      patients were divided into a control group of non-smokers, a moderate smokers
      group and a heavy smokers group. PARTICIPANTS/MATERIALS, SETTING AND METHODS:
      Semen parameters were analysed by standard methods. Sperm DNA integrity and
      mitochondrial activity were assessed by Comet assays and by 3,3'-diaminobenzidine
      deposition, respectively. The level of lipid peroxidation in semen was determined
      by malondialdehyde quantification. Proteomic studies were performed by 2D
      electrophoresis and mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Both
      groups of smokers showed reduced semen quality in comparison with the control
      group. In the groups of smokers, sperm DNA integrity and mitochondrial activity
      were also decreased and lipid peroxidation levels were increased. Proteomic
      analyses revealed 20 proteins differentially expressed between the study groups.
      LIMITATIONS AND REASONS FOR CAUTION: A study including smokers without varicocele
      is still warranted as these results apply only to smokers who present varicocele.
      WIDER IMPLICATIONS OF THE FINDINGS: Patients with varicocele who are exposed to
      tobacco smoking present more important alterations to semen quality and sperm
      functional integrity and show changes in the seminal plasma proteome. This
      suggests testicular, and possibly systemic, adverse effects of smoking. STUDY
      FUNDING/COMPETING INTEREST(S): Funding for the study was provided by Fundacao de
      Amparo a Pesquisa do Estado de Sao Paulo (Fapesp) (2007/59423-7) and by the
      Division of Urology, Human Reproduction Section at the Sao Paulo Federal
      University.

PMID- 22863604
TI  - Propagating waves in thalamus, cortex and the thalamocortical system: Experiments
      and models.
AB  - Propagating waves of activity have been recorded in many species, in various
      brain states, brain areas, and under various stimulation conditions. Here, we
      review the experimental literature on propagating activity in thalamus and
      neocortex across various levels of anesthesia and stimulation conditions. We also
      review computational models of propagating waves in networks of thalamic cells,
      cortical cells and of the thalamocortical system. Some discrepancies between
      experiments can be explained by the "network state", which differs vastly between
      anesthetized and awake conditions. We introduce a network model displaying
      different states and investigate their effect on the spatial structure of self
      sustained and externally driven activity. This approach is a step towards
      understanding how the intrinsically-generated ongoing activity of the network
      affects its ability to process and propagate extrinsic input.

PMID- 22863603
TI  - Cell-free fetal DNA testing for fetal aneuploidy and beyond: clinical integration
      challenges in the US context.
AB  - The recent release of new, non-invasive prenatal tests for fetal aneuploidy using
      cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing
      and has triggered significant commercial interest in the field. Ongoing research
      portends the arrival of a wide range of cffDNA tests. However, it is not yet
      clear how these tests will be integrated into well-established prenatal testing
      strategies in the USA, as the timing of such testing and the degree to which new
      non-invasive tests will supplement or replace existing screening and diagnostic
      tools remain uncertain. We argue that there is an urgent need for policy-makers,
      regulators and professional societies to provide guidance on the most efficient
      and ethical manner for such tests to be introduced into clinical practice in the
      USA.

PMID- 22863605
TI  - Lack of independent relationship between the MMP-12 gene polymorphism and carotid
      plaque susceptibility in the Chinese Han population.
AB  - The purpose of this study was to investigate whether a polymorphism in the matrix
      metalloproteinase-12 gene (MMP-12 -82A/G) is correlated with serum protein levels
      or with the susceptibility for carotid plaques in the Chinese Han population.
      Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was
      performed on the -82A/G polymorphism in the MMP-12 gene for 1314 patients with
      acute cerebral infarctions; 710 of these cases were diagnosed with stable
      plaques, 340 cases were diagnosed with vulnerable plaques and 264 cases had no
      plaques. At the same time, serum MMP-12 levels were measured using the enzyme
      linked immunosorbent assay (ELISA). Compared to the AA genotype, the frequency of
      the AG+GG genotypes was not significantly different between the three groups
      (chi(2) = 1.242, p = 0.537), and the frequency of the G allele of the MMP-12 gene
      was not different within the three subgroups (chi(2) = 1.218, p = 0.544). There
      were no significant differences in MMP-12 protein levels among the three groups
      (F = 0.675, p = 0.510); similarly, there was no difference in MMP-12 protein
      levels between the stable plaque group and the vulnerable plaque group (p =
      0.755). There was also no difference between the vulnerable plaque group and the
      no plaque group (p = 0.420). The current data suggest that the inter-individual
      variability in the MMP-12 gene variation may not be a risk factor for vulnerable
      plaques in the Chinese Han population.

PMID- 22863606
TI  - Well differentiated nonmetastasizing fibrosarcoma (aggressive fibromatosis) of
      mandible: a rare case report and a literature review.
AB  - Fibromatosis in the maxillofacial region is a very rare occurrence among diverse
      pathologic conditions, and because of the rarity of this tumor, definite
      treatment regimen is not established, which may be a contributing factor for a
      high recurrence rate. Fibromatosis may attain a large size and cause compression,
      infiltration, and destruction of adjacent structures. Such growth behavior
      presents severe management problems, especially in the head and neck region,
      where the presence of many vital structures within a small space makes the
      patient susceptible to the effects of the fibromatosis, likewise making complete
      excision difficult. We report the case of a 28-year-old female patient with
      aggressive desmoid fibromatosis involving the mandible, with a literature review
      of postoperative pharmacologic management to prevent recurrence. 

PMID- 22863607
TI  - The burden of serogroup B meningococcal disease.

PMID- 22863608
TI  - Outcomes of invasive meningococcal serogroup B disease in children and
      adolescents (MOSAIC): a case-control study.
AB  - BACKGROUND: Serogroup B meningococcal disease is the commonest cause of
      meningitis and septicaemia in high-income countries. Assessment of new serogroup
      B meningococcal vaccines is hampered by a scarcity of data on the burden of
      disease in survivors. We aimed to estimate the disease burden in children having
      survived serogroup B meningococcal disease. METHODS: In this case-control study,
      we recruited children from the UK National Meningococcal Registry between May,
      2008, and September, 2010. Eligible children were survivors who had had serogroup
      B meningococcal disease confirmed by culture or PCR and were aged 1 month to 13
      years at disease. Age-matched and sex-matched controls were recruited through the
      family doctor of the children who had the meningococcal disease. Physical,
      psychological, neurocognitive, and educational outcomes were assessed through a
      standardised interview with validated instruments. We did matched analyses using
      generalised estimating equations (GEE). Researchers were masked to the children's
      serogroup B meningococcal status. FINDINGS: Of the 537 children who had serogroup
      B meningococcal disease and were available for recruitment, 245 were assessed.
      328 controls were also recruited; 221 controls were matched with a case and 107
      were additional unmatched controls. The mean age was 6.5 (SD 2.8) years in
      children with serogroup B meningococcal disease and 6.9 (2.9) in controls. In the
      full sample, children who had serogroup B meningococcal disease were more likely
      than controls to have bilateral sensorineural hearing loss of 40 dB or more
      (unmatched 11 [5%] of 232 children with meningococcal disease vs three [<1%] of
      318 controls; matched odds ratio [OR] 4.8, 95% CI 1.3 to 17.4, p=0.02), lower
      full-scale IQ (matched mean 99.5 for children with meningococcal disease and
      107.2 for controls; matched coefficient -7.6, 95% CI -9.9 to -5.4, p<0.0001), and
      psychological disorders (61 [26%] of 235 children with meningococcal disease vs
      33 (10%) of 322 controls; matched full sample OR 2.6, 1.6 to 4.2, p<0.0001).
      Disabling amputations were noted in three (1%) of 239 children who had serogroup
      B meningococcal disease compared with none of the 322 controls. Children with
      meningococcal disease were also more likely to have deficits in executive
      function and multiple aspects of memory. Deficits were identified in 87 (36%) of
      244 children with serogroup B meningococcal disease and 49 (15%) of 328 controls
      (matched OR 2.7, 1.8 to 4.1, p<0.0001). Major disabling deficits were identified
      in 21 (9%) of 244 children with meningococcal disease compared with six (2%) of
      328 controls (matched OR 5.0, 2.0 to 12.6, p=0.001). No significant differences
      were noted in attentional function or post-traumatic stress disorder between
      children with serogroup B meningococcal disease and controls. INTERPRETATION:
      Most children survive serogroup B meningococcal disease without major sequelae.
      However, about a tenth have major disabling deficits and more than a third have
      one or more deficits in physical, cognitive, and psychological functioning, with
      the additional burden of memory deficits and executive function problems. These
      findings should help to guide assessments of new vaccines and suggest that all
      survivors of serogroup B meningococcal disease should be screened for
      psychological disorders and cognitive deficits in addition to hearing loss.
      FUNDING: Meningitis Trust and Big Lottery Fund, UK.

PMID- 22863609
TI  - A cell-penetrating bispecific antibody for therapeutic regulation of
      intracellular targets.
AB  - The therapeutic use of antibodies is restricted by the limited access of
      antibodies to intracellular compartments. To overcome this limitation, we
      developed a cell-penetrating monoclonal antibody, mAb 3E10, as an intracellular
      delivery vehicle for the intracellular and intranuclear delivery of antibodies
      constructed as bispecific single-chain Fv fragments. Because MDM2 is an important
      target in cancer therapy, we selected monoclonal antibody (mAb) 3G5 for
      intracellular transport. mAb 3G5 binds MDM2 and blocks binding of MDM2 to p53.
      Here, we show that the resulting 3E10-3G5 bispecific antibody retains cell
      penetrating and MDM2-binding activity, increases tumor p53 levels, and inhibits
      growth of MDM2-addicted tumors. The use of cell-penetrating bispecific antibodies
      in targeted molecular therapy will significantly broaden the spectrum of
      accessible intracellular targets and may have a profound impact in cancer
      therapy.

PMID- 22863610
TI  - Mechanism of drug efficacy within the EGF receptor revealed by microsecond
      molecular dynamics simulation.
AB  - The EGF receptor (EGFR) regulates important cellular processes including
      proliferation, differentiation, and apoptosis. EGFR is frequently overexpressed
      in a range of cancers and is associated with disease progression and treatment.
      Clinical studies have shown that EGFR mutations confer tumor sensitivity to
      tyrosine kinase inhibitors in patients with non-small cell lung cancer. In this
      study, we have conducted molecular dynamics simulations over several microseconds
      for wild-type and L858R mutant forms of EGFR in the ligand-free state. Close
      inspection of the conformations and interactions within the binding pocket
      reveals, converse to the wild type, that the mutant EGFR prefers to bind
      gefitinib, a targeted anticancer drug, rather than ATP, offering an explanation
      for why gefitinib is more effective in patients with EGFR mutations than those
      without.

PMID- 22863611
TI  - Arteriovenous fistula of the filum terminale: radiological diagnosis and
      therapeutic management by embolization.
AB  - A 60-year-old man had progressive paraparesis, paresthesia of both lower limbs
      and sphincter dysfunction. He underwent MRI, which revealed perimedullar abnormal
      vascular channels associated with a hypersignal in the thoracolumbar cord.
      Because of the patient's age and symptomatology, a dural arteriovenous shunt was
      first suspected. MRA confirmed dilatation of the perimedullary venous channels,
      but also revealed an enlarged anterior spinal artery, a finding incompatible with
      a diagnosis of dural arteriovenous fistula. A lesion, vascularized by the
      anterior spinal axis and draining secondarily into the perimedullary veins, was
      thus suspected. Angiography diagnosed a microfistula of the filum terminale;
      selective distal catheterization of the arterial feeder from T11 to S1 was
      achieved, and the shunt closed by embolization with acrylic glue. The patient
      improved after endovascular treatment.

PMID- 22863612
TI  - Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients
      with clinical knee osteoarthritis: a randomised controlled trial.
AB  - OBJECTIVE: To assess the efficacy of thrice daily topical 4Jointz utilizing
      Acteev technology (a combination of a standardized comfrey extract and a
      pharmaceutical grade tannic acid, 3.5 g/day) on osteoarthritic knee pain, markers
      of inflammation and cartilage breakdown over 12 weeks. PATIENTS AND METHODS:
      Adults aged 50-80 years (n = 133) with clinical knee OA were randomised to
      receive 4Jointz or placebo in addition to existing medications. Pain and function
      were measured using a visual analogue scale (VAS) and the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) scale at baseline, 4, 8 and 12 weeks.
      Inflammation was measured analysing IL-6 expression and CTX-2 presence as
      representative for cartilage breakdown using ELISA, at baseline and 12 weeks.
      RESULTS: Pain scores significantly reduced in the group who received 4Jointz
      compared to the group who received placebo after 12 weeks using both the VAS (
      9.9 mm, P = 0.034) and the KOOS pain scale (+5.7, P = 0.047). Changes in IL-6 and
      CTX-2 were not significant (-0.04, P = 0.5; -0.01, P = 0.68). Post-hoc analyses
      suggested that treatment may be most effective in women (VAS -16.8 mm, P = 0.008)
      and those with milder radiographic osteoarthritis (OA) (VAS -16.1 mm, P = 0.009).
      Rates of adverse events were similar in both groups, excepting local rash that
      was more common amongst participants receiving 4Jointz (21% vs 1.6%, IRR 13.2, P
      = 0.013), but only 26% (n = 4) of participants with rashes discontinued
      treatment. There were no changes in systemic blood results. CONCLUSIONS: Topical
      treatment using 4Jointz reduced pain but had no effect on inflammation or
      cartilage breakdown over 12 weeks of treatment. TRIAL REGISTRATION: Australia and
      New Zealand Clinical Trials registry ACTRN12610000877088.

PMID- 22863614
TI  - Public opinion on smoke-free policies among Egyptians.
AB  - SETTING: A smoke-free law was passed in Egypt in 2007. In 2010 a bylaw was
      issued, leading to a drive by the Ministry of Health and Population (MOHP) to
      launch a smoke-free initiative in Alexandria, the second largest city. OBJECTIVE:
      To assess public opinion with regard to 100%  smoke-free legislation and its
      implementation in the Alexandria governorate. DESIGN: The Union Middle-East
      Office, in collaboration with the Central Agency for Public Mobilization and
      Statistics and the MOHP, conducted a cross-sectional survey among 427 randomly
      selected adults (206 males  and 221 females), covering the seven major districts
      of the Alexandria governorate. RESULTS: The majority of the interviewed subjects
      (98%) expressed support of the government in enacting 100% smoke-free indoor
      legislation in all public places and public transport. Respondents endorsed  the
      government plan to implement legislation imposing 100% smoke-free public places.
      More than one third (33.5%) of all respondents indicated that they would increase
      visits to restaurants if they were smoke-free, and 63% indicated no impact at
      all. CONCLUSION: The results of the poll clearly  support results from different
      countries worldwide that smoke-free policies are popular and supported by the
      public.

PMID- 22863613
TI  - Urinary CTX-II concentrations are elevated and associated with knee pain and
      function in subjects with ACL reconstruction.
AB  - OBJECTIVE: Post-traumatic knee osteoarthritis (OA) is prevalent after anterior
      cruciate ligament reconstruction (ACLR). Biomarkers that identify individuals
      likely to develop OA, especially symptomatic OA, can help target preventative and
      therapeutic strategies. This study examined the magnitude and change over time in
      urinary CTX-II (uCTX-II) concentrations shortly after ACL reconstruction, and,
      secondarily, the associations with knee pain and function. DESIGN: Subjects were
      28 patients with ACLR and 28 age- and sex-matched controls (CNTRL). Testing was
      conducted at four time points spaced 4 weeks apart (4, 8, 12 and 16 weeks post
      operative in ACLR). Measures included demographics, urine samples, Numeric Pain
      Rating Scale (NPRS) and International Knee Documentation Committee Subjective
      Knee Form (IKDC-SKF). uCTX-II concentrations were determined with competitive
      enzyme-linked immunosorbent assay (ELISA). uCTX-II concentrations at each time
      point in ACLR were compared to the mean concentration over time in CNTRL, with
      and without adjustment for body mass index (BMI). Changes over time in each
      measure and correlations between the slopes of change were examined. RESULTS:
      uCTX-II concentrations were significantly higher in ACLR than CNTRL through 16
      weeks post-operative when adjusted for BMI. In ACLR, uCTX-II concentrations
      significantly decreased over time, and the slope was associated with NPRS (r =
      0.406, P = 0.039) and IKDC-SKF (r = -0.402, P = 0.034) slopes. CONCLUSION: uCTX
      II concentrations shortly after ACLR were elevated compared to CNTRL and declined
      over time. Decreasing uCTX-II concentrations were associated with decreasing knee
      pain and improving function. uCTX-II may have a role as a prognostic marker
      following ACLR and warrants further investigation.

PMID- 22863615
TI  - Postprandial serum C-peptide is a useful parameter in the prediction of
      successful switching to liraglutide monotherapy from complex insulin therapy in
      Japanese patients with type 2 diabetes.
AB  - AIMS: Liraglutide improves glycemic control in patients with type 2 diabetes.
      However, no information is available about an indicator of successful switching
      to liraglutide monotherapy from complex insulin therapy in Japanese patients with
      type 2 diabetes. METHODS: We studied 69 patients with type 2 diabetes, including
      39 consecutive successful patients and 30 consecutive unsuccessful patients from
      insulin therapy to liraglutide monotherapy. Before switching, we measured urinary
      C-peptide, fasting C-peptide and postprandial C-peptide at 30, 60 and 120 min
      loading a test meal. In successful patients, HbA(1c) and body weight were
      measured at 4, 8, and 12 weeks after switching. RESULTS: Using univariate
      analysis, duration of disease was significantly higher in unsuccessful patients
      than in successful patients. Urinary C-peptide, fasting C-peptide, and
      postprandial C-peptides were significantly higher in successful patients than in
      unsuccessful patients. Multiple logistic regression analysis showed that
      postprandial C-peptide at 60 min was an independent predictor of successful
      switching to liraglutide monotherapy from insulin therapy (odds ratio, 7.28; 95%
      confidence interval, 2.89-18.36). In the receiver operating characteristic
      analyses, 2.9 ng/mL of postprandial C-peptide at 60 min was the best cut-off
      value, providing that sensitivity and specificity were 95% and 93%, respectively.
      In the follow-up period, successful patients showed a sustained reduction in
      HbA(1c) and body weight without hypoglycemia. CONCLUSIONS: Postprandial C-peptide
      at 60 min is a useful parameter in the prediction of successful switching from
      insulin therapy to liraglutide monotherapy in Japanese patients with type 2
      diabetes.

PMID- 22863616
TI  - When NK cells overcome their lack of education.
AB  - Cells of the immune system have evolved various molecular mechanisms to sense
      their environment and react to alterations of self. NK cells are lymphocytes with
      effector and regulatory functions, which are remarkably adaptable to changes in
      self. In a study published in this issue of the JCI, Tarek and colleagues report
      the clinical benefits of manipulating NK cell adaptation to self in an innovative
      mAb-based therapy against neuroblastoma (NB). This novel therapeutic strategy
      should stimulate further research on NK cell therapies.

PMID- 22863617
TI  - Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis.
AB  - Chemotactic cytokines (chemokines) can help regulate tumor cell invasion and
      metastasis. Here, we show that chemokine 25 (CCL25) and its cognate receptor
      chemokine receptor 9 (CCR9) inhibit colorectal cancer (CRC) invasion and
      metastasis. We found that CCR9 protein expression levels were highest in colon
      adenomas and progressively decreased in invasive and metastatic CRCs. CCR9 was
      expressed in both primary tumor cell cultures and colon-cancer-initiating cell
      (CCIC) lines derived from early-stage CRCs but not from metastatic CRC. CCL25
      stimulated cell proliferation by activating AKT signaling. In vivo, systemically
      injected CCR9+ early-stage CCICs led to the formation of orthotopic
      gastrointestinal xenograft tumors. Blocking CCR9 signaling inhibited CRC tumor
      formation in the native gastrointestinal CCL25+ microenvironment, while
      increasing extraintestinal tumor incidence. NOTCH signaling, which promotes CRC
      metastasis, increased extraintestinal tumor frequency by stimulating CCR9
      proteasomal degradation. Overall, these data indicate that CCL25 and CCR9
      regulate CRC progression and invasion and further demonstrate an appropriate in
      vivo experimental system to study CRC progression in the native colon
      microenvironment.

PMID- 22863618
TI  - Natural killer T cells in adipose tissue prevent insulin resistance.
AB  - Lipid overload and adipocyte dysfunction are key to the development of insulin
      resistance and can be induced by a high-fat diet. CD1d-restricted invariant
      natural killer T (iNKT) cells have been proposed as mediators between lipid
      overload and insulin resistance, but recent studies found decreased iNKT cell
      numbers and marginal effects of iNKT cell depletion on insulin resistance under
      high-fat diet conditions. Here, we focused on the role of iNKT cells under normal
      conditions. We showed that iNKT cell-deficient mice on a low-fat diet, considered
      a normal diet for mice, displayed a distinctive insulin resistance phenotype
      without overt adipose tissue inflammation. Insulin resistance was characterized
      by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and
      decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice
      together with the enrichment of CD1d-restricted iNKT cells in both mouse and
      human adipose tissue indicated a specific role for adipose tissue-resident iNKT
      cells in the development of insulin resistance. Strikingly, iNKT cell function
      was directly modulated by adipocytes, which acted as lipid antigen-presenting
      cells in a CD1d-mediated fashion. Based on these findings, we propose that,
      especially under low-fat diet conditions, adipose tissue-resident iNKT cells
      maintain healthy adipose tissue through direct interplay with adipocytes and
      prevent insulin resistance.

PMID- 22863619
TI  - Aneuploidy as a mechanism for stress-induced liver adaptation.
AB  - Over half of the mature hepatocytes in mice and humans are aneuploid and yet
      retain full ability to undergo mitosis. This observation has raised the question
      of whether this unusual somatic genetic variation evolved as an adaptive
      mechanism in response to hepatic injury. According to this model, hepatotoxic
      insults select for hepatocytes with specific numerical chromosome abnormalities,
      rendering them differentially resistant to injury. To test this hypothesis, we
      utilized a strain of mice heterozygous for a mutation in the homogentisic acid
      dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele
      protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver
      disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed
      to chronic liver damage, injury-resistant nodules consisting of Hgd-null
      hepatocytes rapidly emerged. To determine whether aneuploidy played a role in
      this phenomenon, array comparative genomic hybridization (aCGH) and metaphase
      karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically
      enriched in all mice that became completely resistant to tyrosinemia-induced
      hepatic injury. The frequency of chromosome 16-specific aneuploidy was
      approximately 50%. This result indicates that selection of a specific aneuploid
      karyotype can result in the adaptation of hepatocytes to chronic liver injury.
      The extent to which aneuploidy promotes hepatic adaptation in humans remains
      under investigation.

PMID- 22863620
TI  - Modulating inflammatory monocytes with a unique microRNA gene signature
      ameliorates murine ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with
      neuronal cell death that is thought to involve aberrant immune responses. Here we
      investigated the role of innate immunity in a mouse model of ALS. We found that
      inflammatory monocytes were activated and that their progressive recruitment to
      the spinal cord, but not brain, correlated with neuronal loss. We also found a
      decrease in resident microglia in the spinal cord with disease progression. Prior
      to disease onset, splenic Ly6Chi monocytes expressed a polarized macrophage
      phenotype (M1 signature), which included increased levels of chemokine receptor
      CCR2. As disease onset neared, microglia expressed increased CCL2 and other
      chemotaxis-associated molecules, which led to the recruitment of monocytes to the
      CNS by spinal cord-derived microglia. Treatment with anti-Ly6C mAb modulated the
      Ly6Chi monocyte cytokine profile, reduced monocyte recruitment to the spinal
      cord, diminished neuronal loss, and extended survival. In humans with ALS, the
      analogous monocytes (CD14+CD16-) exhibited an ALS-specific microRNA inflammatory
      signature similar to that observed in the ALS mouse model, linking the animal
      model and the human disease. Thus, the profile of monocytes in ALS patients may
      serve as a biomarker for disease stage or progression. Our results suggest that
      recruitment of inflammatory monocytes plays an important role in disease
      progression and that modulation of these cells is a potential therapeutic
      approach.

PMID- 22863623
TI  - Vasculopathy related to cocaine adulterated with levamisole: A review of the
      literature.
AB  - BACKGROUND: Recently, there have been numerous case reports and series describing
      patients presenting with cutaneous vasculopathy that has been linked to the
      levamisole frequently found in cocaine. OBJECTIVE: The purpose of this study was
      to review all published case reports and series of patients reported with
      cutaneous vasculopathic findings of lemavisole induced vasculopathy (LIV)
      associated with cocaine use. METHODS: A review of PubMed was performed searching
      the keywords: levamisole, cocaine, in combination with vasculitis, and
      vasculopathy. Twenty-two case reports and series were available with sufficient
      data on reported patients to be included. Four patients from the authors'
      clinical experience are included as well. RESULTS: A number of common clinical
      and pathological findings are reviewed, including lower extremity (46/55
      patients, 84%) and ear involvement (40/55 patients, 73%), and positive anti
      neutrophil cytoplasmic antibodies (ANCA) findings (p-ANCA 42/48 patients, 88%;
      anti human neutrophil elastase 11/11 patients, 100%). Similar numbers of patients
      were treated with systemic corticosteroids as were treated conservatively; there
      was comparable improvement on follow up. CONCLUSIONS: There are a number of
      clinical and laboratory findings that are commonly found in patients with LIV.
      There is currently insufficient data to recommend treatment with systemic
      corticosteroids in patients with this condition.

PMID- 22863622
TI  - Notch1 counteracts WNT/beta-catenin signaling through chromatin modification in
      colorectal cancer.
AB  - Crosstalk between the Notch and wingless-type MMTV integration site (WNT)
      signaling pathways has been investigated for many developmental processes.
      However, this negative correlation between Notch and WNT/beta-catenin signaling
      activity has been studied primarily in normal developmental and physiological
      processes in which negative feedback loops for both signaling pathways are
      intact. We found that Notch1 signaling retained the capability of suppressing the
      expression of WNT target genes in colorectal cancers even when beta-catenin
      destruction by the adenomatous polyposis coli (APC) complex was disabled.
      Activation of Notch1 converted high-grade adenoma into low-grade adenoma in an
      Apcmin mouse colon cancer model and suppressed the expression of WNT target genes
      in human colorectal cancer cells through epigenetic modification recruiting
      histone methyltransferase SET domain bifurcated 1 (SETDB1). Extensive microarray
      analysis of human colorectal cancers also showed a negative correlation between
      the Notch1 target gene, Notch-regulated ankyrin repeat protein 1 (NRARP), and WNT
      target genes. Notch is known to be a strong promoter of tumor initiation, but
      here we uncovered an unexpected suppressive role of Notch1 on WNT/beta-catenin
      target genes involved in colorectal cancer.

PMID- 22863624
TI  - Two cases of steatocystoma simplex in infants.
AB  - Steatocystoma simplex is a rare benign cutaneous cyst that is thought to be a
      circumscribed malformation arising from the pilosebaceous duct junction. Reports
      describing steatocystoma simplex are scarce and many issues remain to be
      clarified, including frequency and age distribution. Steatocystoma simplex is
      generally considered to be a solitary, non-inherited tumor arising in adults;
      there have been no previous reports of steatocystoma simplex in infants. We
      encountered two cases of steatocystoma simplex arising on the head in infants
      less than 2 years old. Herein we discuss the clinical and pathological
      characteristics of these cases.

PMID- 22863621
TI  - Unlicensed NK cells target neuroblastoma following anti-GD2 antibody treatment.
AB  - Survival outcomes for patients with high-risk neuroblastoma (NB) have
      significantly improved with anti-disialoganglioside GD2 mAb therapy, which
      promotes NK cell activation through antibody-dependent cell-mediated
      cytotoxicity. NK cell activation requires an interaction between inhibitory
      killer cell immunoglobulin-like receptors (KIRs) and HLA class I ligands. NK
      cells lacking KIRs that are specific for self HLA are therefore "unlicensed" and
      hyporesponsive. mAb-treated NB patients lacking HLA class I ligands for their
      inhibitory KIRs have significantly higher survival rates, suggesting that NK
      cells expressing KIRs for non-self HLA are mediating tumor control in these
      individuals. We found that, in the presence of mAb, both licensed and unlicensed
      NK cells are highly activated in vitro. However, HLA class I expression on NB
      cell lines selectively inhibited licensed NK cell activity, permitting primarily
      unlicensed NK cells to mediate antibody-dependent cell-mediated cytotoxicity.
      These results indicate that unlicensed NK cells play a key antitumor role in
      patients undergoing mAb therapy via antibody-dependent cell-mediated
      cytotoxicity, thus explaining the potent "missing KIR ligand" benefit in patients
      with NB.

PMID- 22863625
TI  - Nocardia nova mycetoma over forehead in a lepromatous leprosy patient.
AB  - We present a case of a 31-year-old male, a known patient with lepromatous leprosy
      with a type 2 lepra reaction, who presented with a slowly growing asymptomatic
      swelling with multiple discharging sinuses over the forehead that developed over
      6 months. Smears of the serosanguinous discharge on Gram staining showed Gram
      positive branching filamentous bacilli, which on culture on blood agar showed
      chalky-white colonies. Histology of the lesion showed suppurative granulomas with
      polymorphs surrounding characteristic grains. The isolate was identified as
      Nocardia nova by gene sequencing and the patient was started on combined
      antibiotic therapy that resulted in complete resolution of the infection in six
      months. To the best of our knowledge, this is the first report of mycetoma
      related to Nocardia nova in association with leprosy.

PMID- 22863627
TI  - Fibroepithelioma of Pinkus induced by radiotherapy.
AB  - Fibroepithelioma of Pinkus (FEP) is a rare cutaneous neoplasm. Evidence supports
      classification as a variant of either basal cell carcinoma (BCC) or
      trichoblastoma. Reports of FEP arising in sites of preceding radiation therapy
      have been documented in the literature, but the relationship between radiotherapy
      and the development of FEP has not yet been defined. We report a case of FEP
      following radiation therapy for testicular cancer.

PMID- 22863626
TI  - Keratoacanthoma arising in nevus comedonicus.
AB  - Nevus comedonicus is a benign hamartoma of the pilosebaceous unit and is
      considered as a rare subtype of epidermal nevus. It was first described in 1895.
      It manifests as a group of closely dilated follicular openings with dark keratin
      plugs resembling comedones. Malignant degeneration of a nevus comedonicus is
      exceptional; we report a case of keratoacanthoma arising in extensive nevus
      comedonicus.

PMID- 22863628
TI  - [Pyoderma gangrenosum in an infant: Case report].
AB  - Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of unknown etiology,
      characterized by ulcers, especially on the lower limbs. There have only been 13
      cases of PG in infants (<12 months old) reported in the past 25 years. We report
      the case of a 9-month-old child with ulcers on the right leg diagnosed as
      pyoderma gangrenosum. Tissue cultures for bacteria, mycobacteria, and fungus were
      negative. The child was treated with prednisone 1 mg/Kg/day for 30 days, with
      complete healing of the lesions during this period. No underlying diseases have
      been identified in the last two years, but the child is still being followed.

PMID- 22863629
TI  - Verrucous herpetic infection of the scrotum and the groin in an immuno-competent
      patient: Case report and review of the literature.
AB  - Atypical presentations of genital herpes are more commonly described among immuno
      compromised patients. Furthermore, verrucous lesions may be attributed to
      acyclovir resistant strains of herpes simplex virus as well as co-infection with
      fungi and other viruses in this patient population. We describe the first case of
      verrucous genital herpes infection in an immuno-competent patient.

PMID- 22863630
TI  - Facial angiofibromas in a mosaic pattern tuberous sclerosis: A case report.
AB  - Tuberous sclerosis is a rare genetic disorder presenting clinically with multiple
      hamartomas in different organs including the skin. The cutaneous manifestations
      include facial angiofibromas, hypopigmented macules (ash leaves), connective
      tissue nevi (shagreen patches), and periungual fibromas (Koenen tumors). We
      present a case of facial angiofibromas in a mosaic pattern tuberous sclerosis in
      an 11-year-old boy.

PMID- 22863631
TI  - Multiple poromas in a bone marrow transplant recipient: A case report.
AB  - A poroma is a benign epithelial neoplasm that most commonly presents as a
      solitary papule on the palm or sole. We report the case of a 25-year-old male,
      with a history of acute myelogenous leukemia, who developed multiple poromas on
      the feet. Poromatosis - the occurrence of multiple poromas - has been described
      in six adults and one child; it appears to be more prevalent in patients with a
      history of lymphoproliferative disorder or radiation exposure.

PMID- 22863632
TI  - Cutaneous cholesterol embolization syndrome: A case report.
AB  - An 81-year-old woman with chronic kidney disease, systemic hypertension, and a
      large infra-renal abdominal aortic aneurysm, developed bilateral calf muscle
      pain, altered sensorium, and deterioration of renal function following
      endovascular aneurysmal repair. On the third post-operative day she developed
      symmetrical purpuric macules with erythematous margins on the gluteal region and
      bluish reticulated patches on the soles and tips of toes. This was followed by
      melena development on the seventh post-operative day. Histology of the skin
      confirmed the diagnosis of cutaneous cholesterol embolization syndrome (CES). She
      was treated with hemodialysis and supportive management and she recovered.

PMID- 22863633
TI  - Unknown: A middle-aged woman with a solitary targetoid lesion on her shin.
AB  - We report a 42-year-old woman with an asymptomatic solitary targetoid patch on
      her shin of 1 month duration. Histopathologic evaluation revealed intact
      epidermis with vascular proliferation in the papillary dermis. Vascular channels
      were irregular, thin walled, and dilated. They were lined by prominent
      endothelial cells having plumped protruding nuclei and scanty cytoplasm. There
      was a mild extravasation of red blood cells and mild lymphocytic infiltration
      around blood vessels in the upper and mid dermis.

PMID- 22863634
TI  - Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser.
AB  - Scars sustained following injury in patients with darker skin types can present a
      treatment challenge. These scars often hyperpigment and may remain refractory to
      first line treatments such as topical retinoids and hydroquinone. Additionally,
      more aggressive treatment interventions such as ablative resurfacing, chemical
      peels, and Q-switched laser therapy may actually worsen the pigmentation. We
      describe a 22-year female with a hyperpigmented scar and Fitzpatrick type IV skin
      that improved markedly following treatment with a fractionated erbium doped fiber
      laser. The improvement was maintained at least 1 year following the last
      procedure.

PMID- 22863635
TI  - Letter: Intestinal heterotopia in urethral caruncle.
AB  - We report a case of urethral caruncle with intestinal heterotopia in a 26-year
      old woman. This entity is rarely reported.

PMID- 22863636
TI  - Letter: Alopecia areata during ustekinumab administration: Co-existence or an
      adverse reaction?
AB  - Alopecia areata (AA) is a tissue-specific, T-cell-mediated autoimmune disease
      characterized by non-scarring hair loss. Ustekinumab is a human immunoglobulin
      monoclonal antibody that binds with the p40-subunit of interleukin-12 (IL-12) and
      IL-23 and has been licensed for the treatment of moderate to severe plaque
      psoriasis. The exact pathogenesis of AA remains unclear. However, increased Th1
      serum cytokine levels have been associated with this condition. Thus, IL-12
      inhibitors (ustekinumab) would be expected to treat or at least to prevent hair
      loss. We report two cases of acute AA occurring while on ustekinumab
      administration.

PMID- 22863637
TI  - Letter: Lichenoid eruption induced by etanercept.
AB  - Lichenoid drug eruption is an uncommon, but previously reported, side effect of
      anti-tumor necrosis factor therapy. The majority of these adverse events relate
      to infliximab. We report a patient who developed a lichenoid eruption on the back
      of her hands during etanercept therapy. She improved with topical treatment and
      discontinuation of the drug was not necessary. The physiopathological link
      between anti-TNF treatment and lichenoid eruptions remains unclear. It is
      important to realize that a lichenoid reaction pattern may occur during anti-TNF
      agent treatment.

PMID- 22863638
TI  - Letter: Tinea capitis in infants in their first 2 years of life: A 12-year study
      and a review of the literature.
AB  - BACKGROUND: Tinea capitis (TC) is a dermatophyte infection that occurs mainly in
      childhood; but it is uncommon in infants. The aim of this study was to review the
      clinical and mycological profile of TC in infants. PATIENTS AND METHODS: We
      present a retrospective study; we enrolled all the cases of infant TC over a
      period of 12 years (1999-2010). RESULTS: Thirty-five infants (21 boys, 14 girls)
      with a mean age of 20.16 months were diagnosed with TC among a total number of
      881 cases of TC (3.9%). Scalp scaling and alopecia were the most frequent
      clinical features. Microsporic tinea (21 cases) was the most frequent followed by
      Trichophytic tinea (9 cases) and inflammatory tinea (5 cases). Direct microscopy
      of hair was positive in 33 cases (94.2%). Culture positivity was found in 82.8
      percent of infants (29 cases). Four species of dermatophytes were isolated;
      Microsporum canis in 18 cases (62%) followed by Trichophyton violaceum,
      Trichophyton mentagrophytes, and Trichophyton verrucosum. Twenty-nine infants
      were treated successfully with griseofulvin. DISCUSSION: TC is rare in infants.
      The diagnosis of TC should be considered if scaling and/or alopecia are present
      and should be confirmed by mycology testing prior to initiation of treatment.

PMID- 22863639
TI  - The effect of olive oil on prevention of striae gravidarum: a randomized
      controlled clinical trial.
AB  - OBJECTIVES: Striae gravidarum (SG) is one of the cutaneous physiological changes
      during pregnancy with a high prevalence. This study aimed to evaluate the effect
      of olive oil in prevention of SG. DESIGN: Randomized controlled clinical trial.
      SETTING: Health care centers and three Hospitals affiliated to Tehran University
      of Medical Sciences. PARTICIPANTS: 100 nulliparous pregnant women. INTERVENTIONS:
      Fifty women were randomly allocated to each study group. The treatment group
      received 1 cc topical olive oil twice a day to apply on the abdominal skin in a
      gentle manner without massaging it until the delivery. Control group did not
      receive any cream or oil during the study. MAIN OUTCOME MEASURES: Development of
      SG and its severity was recorded at the end of the study. RESULTS: Although the
      frequency of severe SG was lower in the users of olive oil compared to the other
      group, no statistically significant difference was found between the two
      experimental groups and the control group in the incidence and the severity of
      SG. CONCLUSION: Olive oil reduces the incidence of severe SG and increases the
      incidence of mild SG, but it does not significantly reduce the incidence and the
      severity of SG and it could not be recommended for SG prevention.

PMID- 22863640
TI  - Clinical evaluation of liquid placebos for an herbal supplement, STW5, in healthy
      volunteers.
AB  - BACKGROUND: Although clinical trials are needed to evaluate the efficacy of
      liquid herbal medicinal products, design of feasible placebos that mimic the
      appearance, taste, and smell of such products is particularly challenging.
      OBJECTIVE: The design and feasibility of a liquid placebo for STW5, an herbal
      medicinal product used for various gastrointestinal problems, was explored in
      this study. DESIGN: Four sample products-STW5, a fresh and aged version of a
      placebo made from a seasoning mix (MaggiTM), and a placebo with aged artificial
      flavor and food coloring-were compared in two organoleptic (sensory), single
      blind trials with a total of 60 (N=60) healthy volunteers (n(1)=30, n(2)=30).
      MEASUREMENTS: The appearance, smell, and taste of each solution were evaluated
      using a Likert scale questionnaire. RESULTS: The liquid placebos evaluated were
      similar in regard to appearance, smell, and taste. However, participants
      indicated that for a clinical trial with STW5, the aged MaggiTM placebo would be
      more viable compared to the fresh Maggi placebo or the aged artificial food
      coloring placebo with licorice flavor. Participants also noted that the mint
      flavor and smell of STW5 was distinctly different from the placebo solutions.
      LIMITATIONS: The trials were conducted in healthy volunteers, not in actual
      patients. CONCLUSIONS: The aged MaggiTM liquid mix may be more favorable as a
      placebo than the artificially created one. However, further adjustment will need
      to be made to the MaggiTM placebo to simulate the complex aromatic composition of
      STW5 for clinical studies in the future.

PMID- 22863641
TI  - Back pain amongst mid-age Australian women: a longitudinal analysis of provider
      use and self-prescribed treatments.
AB  - OBJECTIVES: To analyse use of conventional and complementary and alternative
      (CAM) practitioners and self-prescribed CAM amongst mid-age Australian women with
      back pain. DESIGN: Self-completion postal surveys completed in 2004 and 2007, of
      the mid-age cohort of the Australian Longitudinal Study on Women's health.
      Questions asked for written responses about the use of conventional
      practitioners, CAM practitioners and self-prescribed CAM for treatment of back
      pain. SETTING: Analysis of cross-sectional and longitudinal survey data (n=9820),
      conducted as part of the Australian Longitudinal Study on Women's Health (ALSWH),
      which was designed to investigate multiple factors affecting the health and well
      being of women over a 20-year period. MAIN OUTCOME MEASURE: Women were asked if
      they had sought help for back pain in the previous twelve months. RESULTS: The
      prevalence of back pain was 54.8% (n=5383). The percentage of women who sought
      help for their back pain was 17.3% (n=1700). Of the women who sought help for
      back pain, 2% consulted with a CAM practitioner only, 35% consulted a
      conventional practitioner only and 63% with both a conventional and CAM
      practitioner. CONCLUSIONS: Back pain is prevalent amongst mid-age Australian
      women, although only one third sought help. Women who sought help for their back
      pack were high users of CAM (practitioners and self-prescribed) and conventional
      care providers, consulting a CAM practitioner in complement with conventional
      biomedical consultations rather than as an alternative. Further research is
      needed to explore the complex contemporary landscapes of back pain negotiation
      and management.

PMID- 22863643
TI  - Comparative study on the effectiveness of myofascial release manual therapy and
      physical therapy for venous insufficiency in postmenopausal women.
AB  - OBJECTIVES: Venous insufficiency is present in a large number of postmenopausal
      women, increasing their risk of disability. The objective of this study was to
      determine the effects of myofascial release therapy and conventional
      kinesiotherapy on venous blood circulation, pain and quality of life in
      postmenopausal patients with venous insufficiency. METHODS: A randomised
      controlled trial was undertaken. We enrolled 65 postmenopausal women with stage I
      or II venous insufficiency on the clinical, aetiological, anatomical and
      physiopathological (CEAP) scale of venous disorders, randomly assigning them to a
      control (n=32) or experimental (n=33) group. The control and experimental group
      patients underwent physical venous return therapy (kinesiotherapy) for a 10-week
      period, during which the experimental group patients also received 20 sessions of
      myofascial release therapy. Main outcome measures determined pre- and post
      intervention were blood pressure, cell mass, intracellular water, basal
      metabolism, venous velocity, skin temperature, pain and quality of life. RESULTS:
      Basal metabolism (P<0.047), intracellular water (P<0.041), diastolic blood
      pressure (P<0.046), venous blood flow velocity (P<0.048), pain (P<0.039) and
      emotional role (P<0.047) were significantly higher in the experimental group than
      in the control group after the 10-week treatment programme. CONCLUSION: The
      combination of myofascial release therapy and kinesiotherapy improves the venous
      return blood flow, pain and quality of life in postmenopausal women with venous
      insufficiency.

PMID- 22863642
TI  - Prognosis following the use of complementary and alternative medicine in women
      diagnosed with breast cancer.
AB  - OBJECTIVE: The purpose of this study was to assess whether CAM use affected
      breast cancer prognosis in those who did not receive systemic therapy. DESIGN:
      Secondary data analysis of baseline/survey data from the Women's Healthy Eating
      and Living (WHEL) study. 2562 breast cancer survivors participating in the study
      completed baseline assessments and a CAM use questionnaire. Cox regression models
      were conducted to evaluate the use of CAM modalities and dietary supplements on
      time to an additional breast cancer event (mean follow-up=7.3 years). SETTING: A
      US-based multi-site randomized dietary trial. OUTCOME: Time to additional breast
      cancer events. RESULTS: The women who did not receive any systemic treatment had
      a higher risk for time to additional breast cancer events (HR=1.9, 95% CI: 1.32,
      2.73) and for all-cause mortality (HR=1.7, 95% CI: 1.06, 2.73) compared to those
      who had received systemic treatment. Among 177 women who did not receive systemic
      treatment, CAM use was not significantly related to additional breast cancer
      events. There were no significant differences between high supplement users (>=3
      formulations per day) and low supplement users in either risk for additional
      breast cancer events. CONCLUSION: The risk for an additional breast cancer event
      and/or death was higher for those who did not receive any systemic treatments;
      the use of dietary supplements or CAM therapies did not change this risk. This
      indicates that complementary and alternative therapies did not alter the outcome
      of breast cancer and should not be used in place of standard treatment.

PMID- 22863644
TI  - Physiological changes in energy healers during self-practice.
AB  - OBJECTIVE: The physiological status of energy healers during self-practice
      (activating the healing state without the presence of a recipient) has rarely
      been examined. This study assessed self practice-related changes in autonomic
      nervous system (ANS) activity in Reiki Masters and advanced Reconnective Healers.
      DESIGN: Measurements of heart rate (HR), heart rate variability (HRV) and
      cutaneous blood perfusion of the fingers, of 31 Reiki masters and 50 experienced
      Reconnective Healers were made before, during and after self-practice.
      Corresponding measurements were made on 32 control subjects, who gazed at a
      calming picture in place of self-practice. SETTING: Experiments were conducted in
      a laboratory setting. RESULTS: During self-practice by Reconnective Healers, the
      average HR did not change significantly compared to control subjects but the
      average HRV and the root mean square of successive differences in inter-beat
      interval (RMSSD) decreased by 11ms (95% CI 0.6, 4.6, p=0.009) and 13ms (95% CI
      0.2, 4.1, p=0.031) more than in control subjects, respectively, indicating
      reduced parasympathetic nervous activity. Reiki Masters showed no significant
      change in HR, HRV or RMSSD compared to control subjects. Cutaneous blood
      perfusion increased during self-practice relative to control subjects in both
      Reconnective Healers (6.5%; p=0.012) and Reiki Masters (13.7%; p<0.001).
      CONCLUSION: Contrary to expectations, neither Reconnective Healers nor Reiki
      practitioners appear to enter a more physiologically relaxed state during self
      practice although there is a local peripheral vasodilatation that is probably
      mediated by humoral agents.

PMID- 22863645
TI  - Faith and use of complementary and alternative medicine among heart attack
      patients in a secular society.
AB  - OBJECTIVES: To explore the associations of religious and spiritual faith
      (unambiguous, ambiguous and no faith), existential considerations and disease
      severity with use of complementary and alternative medicine (CAM) among heart
      patients in a secular society, and to address patients' perceived influence of
      CAM on their quality of life and heart disease. DESIGN AND SETTING: Prospective
      questionnaire study among 97 consecutively recruited patients (72.2% male; mean
      age 60.6 years) with acute coronary syndrome from a Danish cardiac university
      hospital unit. MAIN OUTCOME MEASURES: Total CAM use in the 6 months following
      hospitalisation. RESULTS: Altogether 24.7% used CAM with dietary/exercise
      counselling and dietary/nutritional supplements being the most prevalent types.
      In a final multivariate logistic regression model entering faith in God, faith in
      a spiritual power and previous CAM use, only unambiguous faith in God predicted
      CAM use following the event (OR: 11.24, CI: 2.19-57.65, p=0.004). No significant
      association was found between heart disease severity and CAM use. The majority of
      CAM treatments were rated as having some degree of positive influence on quality
      of life (75.9%) and the heart disease (58.6%). CONCLUSIONS: Faith among heart
      patients in a secular society was associated with CAM use. It may be speculated
      that believers in God were more inclined to use lifestyle-oriented CAM types such
      as dietary/exercise counselling. Patients' perceived benefits of CAM may be
      strong motivational factors for present or future use. However, considering the
      potential adverse effect of combining some complementary therapies with
      conventional medicine, an open dialogue on CAM use is warranted.

PMID- 22863646
TI  - Development of differential criteria on tongue coating thickness in tongue
      diagnosis.
AB  - OBJECTIVE: To develop differential criteria on the tongue coating thickness
      (TCT), and especially propose the standard for judgment on thin and thick coating
      in tongue diagnosis. METHODS: Sixty oriental medical doctors evaluated the TCT
      (none, thin, and thick coating) in 50 realistic tongue photographs revealing from
      tip-to-root. The photographs were obtained with a digital tongue imaging system
      (DTIS) which measured the percentages of tongue coating on the tongue surface. We
      calculated the match rate which is the ratio in which the assessor's judgment is
      consistent with the decision standard on the tongue coating, and then 24
      assessors (>=80% match rate) were selected to improve the reliability of the
      decision. The agreement level among 24 assessors was examined to assess the inter
      rater reliability. The correlation between TCT judgments and DTIS-measured values
      was examined to ascertain the reliability of DTIS measurements. Finally, the
      assumption probability for the analysis of quantified characteristics of the
      tongue coating was calculated with a proportional odds model. RESULTS: The inter
      rater reliability was assessed as moderate (kappa=0.56) among 24 assessors, the
      level of correlation between TCT judgments and DTIS measurements in 24 assessors
      was relatively high (0.76, p<0.01). As the analysis of the proportional odds
      model, 29.06% was a cut-off point to separate no coating and thin coating, 63.51%
      was a cut-off point to separate thin and thick coating. CONCLUSIONS: The
      differential criteria for TCT in tongue diagnosis were suggested, and
      particularly thick coating is defined as one that tongue coating which tongue
      body is invisible, occupy approximately more than two third areas on the tongue
      surface.

PMID- 22863647
TI  - Substitutes or complements? An exploration of the effect of wait times and
      availability of conventional care on the use of alternative health therapies in
      Canada.
AB  - OBJECTIVES: We explore how alternative and complementary care use is affected by
      wait list length and availability of conventional care in Canada. DESIGN: We use
      data from the 2003 Canadian Community Health Survey, Statistics Canada and the
      Fraser Institute to explore the effect of longer wait times on the use of
      alternative therapies in general and for specific therapies: Registered Massage
      Therapy, Chiropractics, Physiotherapy, Homeopathy and Acupuncture. OUTCOME
      MEASURES: We use binary variables indicating whether the individual used various
      types of alternative care in the year preceding the survey. RESULTS: Wait times
      for specialists are associated with lower probabilities of using alternative
      care, but the effect are usually not statistically significant. Longer wait times
      for non-emergency surgery are associated with lower probabilities of using
      alternative care when using data from CANSIM, but very small higher probabilities
      of using alternative care when using data from the Fraser Institute which
      includes wait times for treatments for other procedures than non-emergency
      surgery. We find positive but extremely small effects for total wait times from
      the Fraser Institute. Individuals reporting unmet health care needs are more
      likely to use alternative care while individuals who do not have a regular
      physician are less likely to use it. CONCLUSIONS: Reporting unmet health care
      needs or no family physician have more of an impact on the use of alternative
      therapies than wait lists do. The evidence is not clear as to whether alternative
      care is sometimes used as a substitute to conventional care rather than a
      complement.

PMID- 22863648
TI  - Status of complementary and alternative medicine in the curricula of health
      colleges in Saudi Arabia.
AB  - OBJECTIVES: To assess the status of complementary and alternative medicine (CAM)
      education in health colleges in Saudi Arabia. METHODS: A cross sectional
      descriptive study was conducted including all medical, dentistry, pharmacy,
      nursing, allied medical science, and health colleges in Saudi Arabia. A semi-
      structured questionnaire was designed to collect information covering CAM tracks,
      courses and contents in the college's curricula, available postgraduates
      programs, continuing medical education activities, number of colleges staff
      members specialized or interested in CAM. RESULTS: Out of 110 health colleges in
      Saudi Arabia, 90 (81.1%) participated in the survey. There is no CAM specialized
      track or postgraduate education in any health college. Eleven (12.2%) colleges
      are teaching CAM courses in their curricula. Fifteen (16.7%) colleges are
      teaching topics related to CAM in different study subjects. Five (5.6%) colleges
      conducted continuing medical education (CME) activities related to CAM. Among
      faculty members, there are only 16 CAM specialists working in 7 colleges and 84
      interested staff members, working in 20 colleges. Colleges of pharmacy are more
      interested in CAM education compared to other colleges with 42.9% (6/14) of them
      have CAM courses in their curricula, (p=0.006). Also, they have more faculty CAM
      specialists (p=0.026) compared to other colleges. CONCLUSION: There is a low and
      diverse attention given to CAM in medical education in Saudi Arabia. There is a
      need for a national plan to review health colleges curricula to prepare health
      care providers for the integration of evidenced based CAM practices.

PMID- 22863649
TI  - Safety protocols for gua sha (press-stroking) and baguan (cupping).
AB  - Gua sha (press-stroking) and Baguan (cupping) are therapeutic procedures of
      traditional East Asian medicine (TEAM) that are also practiced in integrative
      clinical as well as domestic or familial settings. They may be defined as
      instrument assisted mechanical stimulation of the body surface that intentionally
      creates therapeutic petechiae and ecchymosis representing extravasation of blood
      in the subcutis. Blood and 'other potentially infectious material' (OPIM) can
      sometimes be drawn through the surface of the skin leading to potential
      contamination of instruments and to risk of bloodborne pathogen exposure. Neither
      the literature nor the current national standards of the acupuncture profession
      sufficiently address safety standards for Gua sha and Baguan. This paper presents
      the nature of the potential risks and applies current hospital safety standards
      as proposed protocols for Gua sha and Baguan.

PMID- 22863650
TI  - Defining research priorities in complementary medicine in oncology.
AB  - OBJECTIVES: The high usage of complementary and alternative medicines (CAM) by
      cancer patients is increasing, despite limited research available to support
      their use. Therefore identifying research priorities that can inform the evidence
      base for CAM treatment is relevant for many stakeholders, including funders,
      researchers and consumers. DESIGN AND SETTING: Integrative medicine experts,
      oncologists with interest in CAM research, consumer representatives and CAM
      practitioners and researchers took part in a modified Delphi process conducted
      online over three rounds. In round 1 each participant recommended up to five CAM
      research priorities, which were collated and ranked in round 2 by their potential
      usefulness in cancer care, using a Likert scale. In round 3, participants ranked
      the remaining propositions by their ability to impact cancer care in Australia.
      The lowest ranking priorities were eliminated at the completion of each round.
      RESULTS: From the 122 propositions originally submitted by the 27 participants,
      the highest scoring ones included: studying interactions between biologically
      based CAM and conventional cancer treatments, examining CAM effects on quality of
      life, identifying effective communication strategies around CAM, studying the
      role of physical activity in symptom relief and cancer prevention and exploring
      the role of acupuncture in cancer care. CONCLUSION: This method of research
      prioritisation achieved consensus of opinion among a very diverse group of
      stakeholders, invited to collaborate around a highly polarising topic. Through a
      structured interaction, the group agreed on a priority research list acceptable
      to all stakeholders, which can serve as a blueprint for CAM research in oncology
      in Australia.

PMID- 22863651
TI  - Acupoint stimulation intervention for people with primary dysmenorrhea:
      Systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: Primary dysmenorrhea is a common gynecologic complain in women of
      reproductive age. Acupoint stimulation therapies might be an effective
      intervention for primary dysmenorrhea. OBJECTIVE: The aim of this study was to
      determine the effectiveness of acupoint stimulation for primary dysmenorrhea.
      DATA SOURCES: All searches in the Cochrane Library, MEDLINE, PubMed, CINAHL Plus
      with Full Text, and CEPS databases (inception to March 2011). STUDY SELECTION:
      Randomized controlled trials (RCTs) included were comparing acupoint stimulation
      with non-acupoint-related stimulation or medication. DATA EXTRACTION: Data were
      abstracted independently by two authors onto standardized forms, and
      disagreements were resolved by discussion. DATA SYNTHESIS: Thirty RCTs met the
      selection criteria, and 25 reported sufficient data for pooling. The main
      outcomes assessed were cure rate, total effective rate, pain intensity, menstrual
      pain, plasma PGF(2alpha)/PGE(2) ratio, and adverse events. According to the type
      of outcome, the strength of a relationship between two dichotomous variables was
      described by odds ratios and 95% confidence intervals, and continuous variables
      were expressed as mean+/-standard deviation. Fixed-effects models were used to
      perform meta-analysis. RESULTS: Twenty-five RCTs with a total of over 3000
      participants were included for the meta-analysis. Acupoint stimulation when
      compared with non-acupoint-related stimulation or medication had significant
      effects. Moderator analysis further confirmed that invasive and noninvasive
      acupoint stimulation was effective separately, with the latter being more
      effective. The most common adverse events were hemorrhage and hematoma.
      LIMITATIONS: Papers written in language other than English or Chinese were not
      included. CONCLUSIONS AND IMPLICATION: This finding indicates that acupoint
      stimulation, especially non-invasive acupoint stimulation, could have good short
      term effects on pain of primary dysmenorrhea. Inference in some studies was
      somewhat restricted due to low methodological rigor. We suggest well-designed,
      methodologically rigorous, large trial, evaluating both short and long-term
      effects on pain and other outcomes in comparison with the available standard
      treatments.

PMID- 22863652
TI  - Costs and consequences of acupuncture as a treatment for chronic pain: a
      systematic review of economic evaluations conducted alongside randomised
      controlled trials.
AB  - BACKGROUND: The economic burden that chronic pain conditions impose on
      individuals and society is significant. Acupuncture appears to be a clinically
      effective treatment for some chronic pain conditions. Given the need for policy
      decisions to be informed by economic evaluations, the objective of this
      systematic review was to synthesise data from economic evaluations to determine
      whether acupuncture for the treatment of chronic pain conditions is good value
      for money. METHODS: A literature search was conducted using health and economics
      databases, with additional hand-searching. Economic evaluations conducted
      alongside randomised controlled trials were eligible. RESULTS: Eight economic
      evaluations were included in this review, seven cost-utility analyses and one
      cost-effectiveness analysis. Conditions treated included low back pain, neck
      pain, dysmenorrhoea, migraine and headache, and osteoarthritis. From the seven
      cost-utility analyses, acupuncture was found to be clinically effective but cost
      more. The cost per quality adjusted life year (QALY) gained ranged from L2527 to
      L14,976 per QALY, below the commonly quoted threshold used by the UK National
      Institute for Health and Clinical Excellence of L20,000 to L30,000. The one cost
      effectiveness study indicated that there might be both clinical benefits and cost
      savings associated with acupuncture for migraine. There was heterogeneity across
      the eight trials in terms of professional who provided the acupuncture, style of
      acupuncture, and country of origin. CONCLUSION: The cost per QALY gained in all
      seven cost-utility studies was found to be below typical thresholds of
      willingness to pay. Acupuncture appears to be a cost-effective intervention for
      some chronic pain conditions.

PMID- 22863653
TI  - 5-HT(1A) receptor binding changes in patients with major depressive disorder
      before and after antidepressant treatment: a pilot [18F]MPPF positron emission
      tomography study.
AB  - This is the first [18F]MPPF PET study in positron emission tomography study in
      depressed patients, both before and after treatment with a selective serotonin
      reuptake inhibitor (SSRI). Dynamic changes in [18F]MPPF binding potential were
      observed primarily in the medial orbital regions from baseline to 30 days of
      treatment, suggesting SSRI-mediated serotoninergic adaptative mechanisms.

PMID- 22863655
TI  - Overcoming C2 deficiency.

PMID- 22863654
TI  - Age effect on subcortical structures in healthy adults.
AB  - Cross-sectional age effects in normal control volunteers were investigated using
      magnetic resonance imaging in the following eight subcortical structures: lateral
      ventricles, thalamus, caudate, putamen, pallidum, hippocampus, amygdala and
      nucleus accumbens. Two hundred and twenty-six control subjects, ranging in age
      from 19 to 85 years, were scanned on a 1.5 T GE system (n=184) or a 3.0 T Siemens
      system (n=42). Volumes of subcortical structures, adjusted for cranium size, were
      estimated using FSL's FIRST software, which is fully automated. Significant age
      effects were found for all volumes when the entire age range was analyzed;
      however, the older subjects (60-85 years of age) showed a stronger correlation
      between age and structural volume for the ventricles, hippocampus, amygdala and
      accumbens than middle-aged (35-60 years of age) subjects. Middle-aged subjects
      were studied at both sites, and age effects in these groups were comparable,
      despite differences in magnet strength and acquisition systems. This agreement
      lends support to the validity of the image-analysis tools and procedures used in
      the present study.

PMID- 22863656
TI  - Ascorbate oxidase: the unexpected involvement of a 'wasteful enzyme' in the
      symbioses with nitrogen-fixing bacteria and arbuscular mycorrhizal fungi.
AB  - Ascorbate oxidase (AO, EC 1.10.3.3) catalyzes the oxidation of ascorbate (AsA) to
      yield water. AO over-expressing plants are prone to ozone and salt stresses,
      whereas lower expression apparently confers resistance to unfavorable
      environmental conditions. Previous studies have suggested a role for AO as a
      regulator of oxygen content in photosynthetic tissues. For the first time we show
      here that the expression of a Lotus japonicus AO gene is induced in the symbiotic
      interaction with both nitrogen-fixing bacteria and arbuscular mycorrhizal (AM)
      fungi. In this framework, high AO expression is viewed as a possible strategy to
      down-regulate oxygen diffusion in root nodules, and a component of AM symbiosis.
      A general model of AO function in plants is discussed.

PMID- 22863658
TI  - A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster
      vaccination of healthy Mexican children.
AB  - OBJECTIVES: To evaluate an investigational, fully liquid hexavalent diphtheria
      tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus
      influenzae type b (DTaP-IPV-Hep B-PRP-T: HexaximTM) vaccine for primary and
      booster vaccination of healthy children in Mexico. METHODS: Infants (N=1189) were
      randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a
      licensed hexavalent control vaccine (InfanrixTM hexa) for primary vaccination at
      2, 4 and 6 months. All participants who completed the primary series and agreed
      to participate in the booster part of the study received a dose of the
      investigational vaccine at 15-18 months of age. Validated serological assays and
      parental reports were used to assess immunogenicity and safety, respectively.
      RESULTS: Post-primary vaccination, >=95.8% of participants in both the DTaP-IPV
      Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria,
      tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the
      pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The
      SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No
      differences in SP/SC rates were observed between the pooled lots of
      investigational vaccine and the control vaccine. Antibody persistence at 15-18
      months was comparable between groups, with strong increases in all antibody
      concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well
      tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP
      T. CONCLUSION: These study findings confirm the suitability of the combined,
      fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood
      vaccination schedules.

PMID- 22863657
TI  - Simplifying complex sequence information: a PCP-consensus protein binds
      antibodies against all four Dengue serotypes.
AB  - Designing proteins that reflect the natural variability of a pathogen is
      essential for developing novel vaccines and drugs. Flaviviruses, including Dengue
      (DENV) and West Nile (WNV), evolve rapidly and can "escape" neutralizing
      monoclonal antibodies by mutation. Designing antigens that represent many
      distinct strains is important for DENV, where infection with a strain from one of
      the four serotypes may lead to severe hemorrhagic disease on subsequent infection
      with a strain from another serotype. Here, a DENV physicochemical property (PCP)
      consensus sequence was derived from 671 unique sequences from the Flavitrack
      database. PCP-consensus proteins for domain 3 of the envelope protein (EdomIII)
      were expressed from synthetic genes in Escherichia coli. The ability of the
      purified consensus proteins to bind polyclonal antibodies generated in response
      to infection with strains from each of the four DENV serotypes was determined.
      The initial consensus protein bound antibodies from DENV-1-3 in ELISA and Western
      blot assays. This sequence was altered in 3 steps to incorporate regions of
      maximum variability, identified as significant changes in the PCPs,
      characteristic of DENV-4 strains. The final protein was recognized by antibodies
      against all four serotypes. Two amino acids essential for efficient binding to
      all DENV antibodies are part of a discontinuous epitope previously defined for a
      neutralizing monoclonal antibody. The PCP-consensus method can significantly
      reduce the number of experiments required to define a multivalent antigen, which
      is particularly important when dealing with pathogens that must be tested at
      higher biosafety levels.

PMID- 22863659
TI  - Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l
      carriers, and further enhanced in patients with a history of symptomatic primary
      infection.
AB  - OBJECTIVE: Epstein-Barr virus (EBV) infection is an established risk factor for B
      cell lymphomas in Human Immunodeficiency virus (HIV)-1 infected patients. A
      disturbed EBV-host relationship is seen in patient groups with a high risk for
      EBV-associated lymphomas. We have analysed this relationship by measuring EBV-DNA
      in the blood of HIV-1 carriers. METHOD: EBV-DNA load in B-cells was monitored by
      PCR in non- or insufficiently antiretroviral treated and rgp160-vaccinated HIV
      patients. RESULTS: Both asymptomatic HIV-infected and AIDS-patients showed a 25
      40-fold increase in the number of B cell associated EBV-DNA copies compared to
      healthy controls. Patients included in a vaccine trial with recombinant HIV gp160
      showed a 5-fold increase of EBV load compared to non-immunised patients and a 50
      fold increase compared to healthy controls. There was no difference whether they
      received vaccine or "placebo". Vaccinated patients with a history of symptomatic
      primary HIV-1 infection (PHI) had a 280-fold increase in median EBV load compared
      to healthy controls, thus suggesting a synergistic effect between the vaccination
      and PHI, which hypothetically could affect lymphoma risk. CONCLUSIONS: We
      recommend analysis of EBV-load and long term follow up of lymphoma risk in all
      therapeutic HIV-1 vaccination trials.

PMID- 22863660
TI  - Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds
      previously vaccinated against yellow fever: randomized, controlled, phase II
      study in Piura, Peru.
AB  - In a randomized, placebo-controlled, monocenter, observer blinded study conducted
      in an area where dengue is endemic, we assessed the safety and immunogenicity of
      a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV)
      in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due
      to vaccination 1-7 years previously. 199 children received 3 injections of CYD
      TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal
      polysaccharide vaccine (month 12). One month after the third dengue vaccination,
      serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil)
      (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and
      94% of vaccines were seropositive to all four serotypes (versus 39% in the
      control group). There were no vaccine-related SAEs. The observed reactogenicity
      profile was consistent with phase I studies, with severity grade 1-2 injection
      site pain, headache, malaise and fever most frequently reported and no increase
      after subsequent vaccinations. Virologically confirmed dengue cases were seen
      after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the
      control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2
      11 year olds with a history of YF vaccination and elicited robust antibody
      responses that were balanced against the four serotypes.

PMID- 22863661
TI  - The financial impact of a state adopting a personal/philosophical belief
      exemption policy: modeling the cost of pertussis disease in infants, children and
      adolescents.
AB  - State school immunization exemption policies help reduce the risk of individual
      and community disease. Assessing the costs of vaccine preventable disease
      associated with a state adding a philosophical/personal belief school exemption
      policy is useful for making future policy decisions. Two formulas were developed
      to estimate the infant, child and adolescent hospitalization and non-medical
      costs of pertussis disease that are associated with adding a
      philosophical/personal belief school exemption policy. The parameter estimates
      were obtained from peer reviewed literature and the Centers for Disease Control
      and Prevention. The state of Iowa was used as an example in order to demonstrate
      how the formulas can be applied. The annual projected impact of pertussis disease
      in Iowa is $273,365 without a philosophical/personal belief exemption policy and
      an average of $410,047 (range of $281,566-$582,267) with adding a personal belief
      exemption policy. We project that adding a philosophical/personal belief
      exemption will cost 50% more dollars annually.

PMID- 22863663
TI  - Enhanced medical rehabilitation increases therapy intensity and engagement and
      improves functional outcomes in postacute rehabilitation of older adults: a
      randomized-controlled trial.
AB  - OBJECTIVES: For millions of disabled older adults each year, postacute care in
      skilled nursing facilities is a brief window of opportunity to regain enough
      function to return home and live independently. Too often this goal is not
      achieved, possibly because of therapy that is inadequately intense or engaging.
      This study tested Enhanced Medical Rehabilitation, an intervention designed to
      increase patient engagement in, and intensity of, daily physical and occupational
      therapy sessions in postacute-care rehabilitation. DESIGN: Randomized controlled
      trial of Enhanced Medical Rehabilitation versus standard-of-care rehabilitation.
      SETTING: Postacute care unit of a skilled nursing facility in St Louis, MO.
      PARTICIPANTS: Twenty-six older adults admitted from a hospital for postacute
      rehabilitation. INTERVENTION: Based on models of motivation and behavior change,
      Enhanced Medical Rehabilitation is a set of behavioral skills for physical and
      occupational therapists that increase patient engagement and intensity, with the
      goal of improving functional outcome, through (1) a patient-directed, interactive
      approach, (2) increased rehabilitation intensity, and (3) frequent feedback to
      patients on their effort and progress. MEASUREMENTS: Therapy intensity:
      assessment of patient active time in therapy sessions. Therapy engagement:
      Rehabilitation Participation Scale. Functional and performance outcomes: Barthel
      Index, gait speed, and 6-minute walk. RESULTS: Participants randomized to
      Enhanced Medical Rehabilitation had higher intensity therapy and were more
      engaged in their rehabilitation sessions; they had more improvement in gait speed
      (improving from 0.08 to 0.38 m/s versus 0.08 to 0.22 in standard of care, P =
      .003) and 6-minute walk (from 73 to 266 feet versus 40 to 94 feet in standard of
      care, P = .026), with a trend for better improvement of Barthel Index (+43 points
      versus 26 points in standard of care, P = .087), compared with participants
      randomized to standard-of-care rehabilitation. CONCLUSION: Higher intensity and
      patient engagement in the postacute rehabilitation setting is achievable, with
      resultant better functional outcomes for older adults. Findings should be
      confirmed in a larger randomized controlled trial.

PMID- 22863662
TI  - Immortalization of neuronal progenitors using SV40 large T antigen and
      differentiation towards dopaminergic neurons.
AB  - Transplantation is common in clinical practice where there is availability of the
      tissue and organ. In the case of neurodegenerative disease such as Parkinson's
      disease (PD), transplantation is not possible as a result of the non-availability
      of tissue or organ and therefore, cell therapy is an innovation in clinical
      practice. However, the availability of neuronal cells for transplantation is very
      limited. Alternatively, immortalized neuronal progenitors could be used in
      treating PD. The neuronal progenitor cells can be differentiated into
      dopaminergic phenotype. Here in this article, the current understanding of the
      molecular mechanisms involved in the differentiation of dopaminergic phenotype
      from the neuronal progenitors immortalized with SV40 LT antigen is discussed. In
      addition, the methods of generating dopaminergic neurons from progenitor cells
      and the factors that govern their differentiation are elaborated. Recent advances
      in cell-therapy based transplantation in PD patients and future prospects are
      discussed.

PMID- 22863665
TI  - ApoE and quality of life in nonagenarians.
AB  - OBJECTIVES: ApoE epsilon4 is associated with adverse health conditions that
      negatively impact the quality of life (QOL). The relationship between ApoE
      epsilon4 and QOL has not been explored in the oldest old. Our study aimed to
      examine ApoE in the oldest old and explore its association with QOL. DESIGN:
      Cross-sectional cohort study. SETTING: A medium sized community in Olmsted
      County, Minnesota. PARTICIPANTS: Individuals aged 90 to 99 years, living
      independently or in long term care environments. MEASUREMENTS: We collected
      demographic information and measured cognitive function (Short Test of Mental
      Status, Mini-Mental State Examination, Mattis Dementia Rating Scale), QOL (Linear
      Analogue Self Assessment), and ApoE distribution. Subjects were classified as
      cognitively normal, mild cognitive impairment, dementia, or dementia with stroke
      and/or parkinsonism (DEMSP). Regression model was used to assess the predictors
      of QOL. RESULTS: A total of 121 subjects (45 cognitively normal, 13 with mild
      cognitive impairment, 34 with dementia, 29 DEMSP) aged 90-99 years, 106 (87.6 %)
      females, were included. Frequency of ApoE epsilon3 allele was highest (194
      [80.2%]: epsilon2/3 18, epsilon3/3 77, epsilon3/4 22) followed by ApoE epsilon4
      (25 [10.3%]: epsilon2/4 3, epsilon3/4 22) and ApoE epsilon2 (23 [9.5%; epsilon2/2
      1, epsilon2/3 18, epsilon2/4 3). None of the subjects carried ApoE epsilon4/4
      genotype. QOL was similar between ApoE epsilon4 carrier and noncarriers. Physical
      well-being, emotional well-being, intellectual well-being, social connectedness,
      and coping ability were positively associated with QOL, whereas male sex, DEMSP,
      pain frequency, and pain severity were negatively associated. CONCLUSIONS: The
      most common ApoE in the oldest old was epsilon3/3 genotype and epsilon3 allele.
      No association was found between ApoE epsilon4 and QOL. However, those with high
      physical, emotional and intellectual well being, social connectedness, and coping
      ability had the highest overall QOL.

PMID- 22863667
TI  - Pathophysiological roles of endothelin receptors in cardiovascular diseases.
AB  - Endothelin (ET)-1 derived from endothelial cells has a much more important role
      in cardiovascular system regulation than the ET-2 and ET-3 isoforms. Numerous
      lines of evidence indicate that ET-1 possesses a number of biological activities
      leading to cardiovascular diseases (CVD) including hypertension and
      atherosclerosis. Physiological and pathophysiological responses to ET-1 in
      various tissues are mediated by interactions with ET(A)- and ET(B)-receptor
      subtypes. Both subtypes on vascular smooth muscle cells mediate vasoconstriction,
      whereas the ET(B)-receptor subtype on endothelial cells contributes to
      vasodilatation and ET-1 clearance. Although selective ET(A)- or nonselective
      ET(A)/ET(B)-receptor antagonisms have been assumed as potential strategies for
      the treatment of several CVD based on clinical and animal experiments, it remains
      unclear which antagonisms are suitable for individuals with CVD because
      upregulation of the nitric oxide system via the ET(B) receptor is responsible for
      vasoprotective effects such as vasodilatation and anti-cell proliferation. In
      this review, we have summarized the current understanding regarding the role of
      ET receptors, especially the ET(B) receptor, in CVD.

PMID- 22863666
TI  - N-type calcium channel inhibition with cilnidipine elicits glomerular podocyte
      protection independent of sympathetic nerve inhibition.
AB  - We recently demonstrated that cilnidipine, an L/N-type calcium channel blocker,
      elicits protective effects against glomerular podocyte injury, in particular, in
      obese hypertensive rats that express the N-type calcium channel (N-CC). Since the
      N-CC is known to be expressed in sympathetic nerve endings, we evaluated the reno
      protective effects of cilnidipine in innervated and denervated spontaneously
      hypertensive rats (SHR). Male SHR were uninephrectomized and fed 4% high-salt
      diet (HS-UNX-SHR). Animals were divided into groups, as follows, and observed
      from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation
      (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; n = 10), and 4) cilnidipine
      plus renal-denervation (n = 15). Renal denervation attenuated elevations in blood
      pressure, but failed to suppress urinary protein excretion and podocyte injury in
      HS-UNX-SHR. Cilnidipine in both innervated and denervated HS-UNX-SHR similarly
      induced significant antihypertensive effects, as well as suppressing the urinary
      protein excretion and podocyte injury, compared to vehicle-treated HS-UNX-SHR.
      These data indicate that renal nerves have a limited contribution to the
      cilnidipine-induced reno-protective effects in HS-UNX-SHR.

PMID- 22863668
TI  - Constitutive and conditional mutant mouse models for understanding dopaminergic
      regulation of orofacial movements: emerging insights and challenges.
AB  - Among numerous mechanisms implicated in the regulation of orofacial movements,
      dopamine-containing neurons have received the most extensive study. Here we
      review the effects of a) constitutive knockout of D(1-5) dopamine receptors and
      b) conditional mutations with progressive ablation of D(1) receptor-expressing
      cells, on the topography of spontaneous and D(1)-like agonist-induced orofacial
      movements. In constitutive knockouts, D(1) and D(2) exert primary roles in
      regulating horizontal and vertical jaw movements, respectively, in opposite
      directions; in contrast, both D(1) and D(2) receptors regulate tongue protrusions
      and incisor chattering, in the same direction. D(3) and D(5) receptors play more
      subtle roles in regulating orofacial movements, while D(4) receptors do not play
      any material role. Progressive loss of forebrain D(1) receptor-expressing cells
      in CamKIIa/Cre D(1)Tox mutants is associated primarily with decreases in head and
      vibrissae movements, while progressive loss of striatal D(1) receptor-expressing
      cells in DARPP-32/Cre D(1)Tox mutants is associated primarily with reductions in
      jaw movements and tongue protrusions but increases in head and vibrissae
      movements. Further application of constitutive and particularly conditional
      mutants may clarify further not only dopaminergic regulation of orofacial
      movements but also the pathophysiology of orofacial dysfunction in Huntington's
      disease and Parkinson's disease.

PMID- 22863669
TI  - Effect of renal impairment on the pharmacokinetics of memantine.
AB  - The effect of renal impairment on the pharmacokinetics of a single oral dose of
      memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to
      four groups based on baseline creatinine clearance (CL(CR)): normal renal
      function (> 80 mL/min, n = 6), and mild (50 to <= 80 mL/min, n = 6), moderate (30
      to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7).
      Mean memantine maximum plasma concentration (C(max)) was similar in the groups
      (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to C(max)
      (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine
      determined from mean area under the plasma concentration-time curve was 1.62-,
      1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal
      impairment, respectively, as compared to controls with normal renal function.
      Mean memantine plasma elimination half-life increased according to increasing
      renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean
      cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased
      according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%,
      respectively). These results are the same as those in the previous study on
      caucasian individuals, when compared per body weight. It is suggested that the
      dose of memantine should be halved in patients with renal impairment.

PMID- 22863670
TI  - Neural correlates of the semantic interference effect: new evidence from
      transcranial direct current stimulation.
AB  - In two experiments, we combined a semantic blocked naming paradigm with anodal
      transcranial direct current stimulation (tDCS) to shed light on the neural
      correlates of the semantic interference (SI) effect. In particular, prior to the
      naming task, anodal tDCS was applied over the left superior temporal gyrus (STG,
      Experiment 1) or the left inferior frontal gyrus (IFG, Experiment 2) to enhance
      cortical excitability in these regions. In both experiments, participants were
      tested in two sessions in which either real or sham tDCS was delivered. We found
      that anodal tDCS over the left STG significantly increased the SI effect, whereas
      anodal tDCS over the left IFG led to a reduction of the SI effect. Overall, our
      data confirm the existence of a distributed cortical network involved in lexical
      retrieval and show that both the left IFG and the left STG play a causal role in
      this process. In particular, the left IFG is likely to be critical in resolving
      the conflict between competitor lexical representations, while the left STG seems
      to be the neural locus of the lexical representational system, where competition
      among different lexical representations occurs.

PMID- 22863671
TI  - The effect of nerve compression and capsaicin on contact heat-evoked potentials
      related to Adelta- and C-fibers.
AB  - Brief noxious heat stimuli activate Adelta- and C-fibers and allow contact heat
      evoked potentials (CHEPs) to be recorded from the scalp. Under normal conditions,
      only late responses related to Adelta-fibers can be recorded. This study aimed to
      demonstrate C-fiber responses to contact heat stimuli. A preferential A-fiber
      compression blockade of the superficial radial nerve was applied in 22 healthy
      subjects. Quality and intensity of heat-evoked pain and CHEPs were examined at
      baseline, during nerve compression, and during nerve compression with
      simultaneous application of topical capsaicin (5%). During the A-fiber block,
      three subjects had CHEPs with latencies below 400 ms, eight subjects within 400
      800 ms and six subjects (29%) later than 800 ms. Pain intensity to contact heat
      stimuli after compression was reduced and fewer subjects reported the heat
      stimuli as stinging. Following nerve compression and capsaicin application,
      ultralate CHEPs with latencies >800 ms could be recorded in 13 subjects (62%),
      pain intensity to the contact heat stimuli was increased and the warm/hot-burning
      pain quality became more intense. The main results of our study are the
      demonstration of ultralate C-fiber-related CHEPs following A-fiber blockade in
      29% of healthy subjects increasing to 62% when the blockade was combined with
      capsaicin. After blockade of Adelta-fibers we recorded responses with latencies
      in the range between the latencies of Adelta- and C-fibers suggesting release of
      Adelta-fibers with slower conduction velocity than normally recorded with CHEPs.

PMID- 22863672
TI  - Glucocorticoid receptors and extinction retention deficits in the single
      prolonged stress model.
AB  - Single prolonged stress (SPS) is a rodent model of post traumatic stress disorder
      that is comprised of serial application of restraint (r), forced swim (fs), and
      ether (eth) followed by a 7-day quiescent period. SPS induces extinction
      retention deficits and it is believed that these deficits are caused by the
      combined stressful effect of serial exposure to r, fs, and eth. However, this
      hypothesis remains untested. Neurobiological mechanisms by which SPS induces
      extinction retention deficits are unknown, but SPS enhances glucocorticoid
      receptor (GR) expression in the hippocampus, which is critical for contextual
      modulation of extinction retrieval. Upregulation of GRs in extinction circuits
      may be a mechanism by which SPS induces extinction retention deficits, but this
      hypothesis has not been examined. In this study, we systematically altered the
      stressors that constitute SPS (i.e. r, fs, eth), generating a number of partial
      SPS (p-SPS) groups, and observed the effects SPS and p-SPSs had on extinction
      retention and GR levels in the hippocampus and prefrontal cortex (PFC). PFC GRs
      were assayed, because regions of the PFC are critical for maintaining extinction.
      We predicted that only exposure to full SPS would result in extinction retention
      deficits and enhance hippocampal and PFC GR levels. Only exposure to full SPS
      induced extinction retention deficits. Hippocampal and PFC GR expression was
      enhanced by SPS and most p-SPSs, however hippocampal GR expression was
      significantly larger following the full SPS exposure than all other conditions.
      Our findings suggest that the combined stressful effect of serial exposure to r,
      fs, and eth results in extinction retention deficits. The results also suggest
      that simple enhancements in GR expression in the hippocampus and PFC are
      insufficient to result in extinction retention deficits, but raise the
      possibility that a threshold-enhancement in hippocampal GR expression contributes
      to SPS-induced extinction retention deficits.

PMID- 22863673
TI  - The repetition timing of high frequency afferent stimulation drives the
      bidirectional plasticity at central synapses in the rat medial vestibular nuclei.
AB  - In this study we show that high frequency stimulation (HFS, 100Hz) of afferent
      fibers to the medial vestibular nucleus (MVN) can induce opposite long-term
      modifications of synaptic responses in the type B neurons depending upon the
      stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation
      (SBS: 0.55s) were applied with different burst number (BN) and inter-burst
      intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d
      aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term
      depression (LTD), depending on temporal organization of repetitive bursts. In
      particular, the IBI plays a relevant role in guiding the shift from LTP to LTD
      since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By
      contrast, the sign of long-term effect does not depend on the mean impulse
      frequency evaluated within the entire stimulation period. Therefore, the patterns
      of repetitive vestibular activation with different ratios between periods of
      increased activity and periods of basal activity may lead to LTP or LTD probably
      causing different levels of postsynaptic Ca(2+). On the whole, this study
      demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR
      dependent bidirectional plasticity and puts forward a new aspect for
      understanding the adaptive and compensatory plasticity of the oculomotor
      responses.

PMID- 22863675
TI  - Tonotopic-column-dependent variability of neural encoding in the auditory cortex
      of rats.
AB  - Neural computation could benefit from the heterogeneity of neurons to achieve
      energy efficiency. Beyond a single neuron level, adaptation to biologically
      important signals should also make functional columns heterogeneous. In the
      present study, we test a hypothesis that variability of neural response depends
      on tonotopic columns in the primary auditory cortex (A1) of rats. Mutual
      information (MI) was estimated from multi-unit responses in A1 of anesthetized
      rats, to quantify how spike count (SC) and the first spike latency (FSL) carried
      information about frequency and intensity of test tones. Consequently, for both
      SC and FSL, we found best frequency (BF)-dependent MI distributions with wide
      variances in high BF regions. These MI distributions were caused by BF-dependence
      of the amount of information that neurons conveyed, i.e., total entropy, rather
      than the transmission efficiency. In addition, the relationship between the
      transmission efficiency and the total entropy differentiated SC encoding and FSL
      encoding, suggesting that SC encoding and FSL encoding are not redundant but each
      plays a different role in intensity encoding. These results provide compelling
      evidence that BF columns are heterogeneous. Such heterogeneity of columns may
      make the global computation in A1 more efficient. Thus, the efficient coding in
      the neural system could be achieved by multiple-scale heterogeneity.

PMID- 22863674
TI  - Cannabinoid-1 receptors in the mouse ventral pallidum are targeted to axonal
      profiles expressing functionally opposed opioid peptides and contacting N
      acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals.
AB  - The ventral pallidum (VP) is a major recipient of inhibitory projections from
      nucleus accumbens (Acb) neurons that differentially express the reward
      (enkephalin) and aversion (dynorphin)-associated opioid peptides. The cannabinoid
      1 receptor (CB1R) is present in Acb neurons expressing each of these peptides,
      but its location in the VP is not known. To address this question, we used
      electron microscopic dual immunolabeling of the CB1R and either dynorphin 1-8
      (Dyn) or Met(5)-enkephalin (ME) in the VP of C57BL/6J mice, a species in which
      CB1R gene deletion produces a reward deficit. We also used similar methods to
      determine the relationship between the CB1R and N-acylphosphatidylethanolamine
      (NAPE)-hydrolyzing phospholipase D (NAPE-PLD), an anandamide-synthesizing enzyme
      located presynaptically in other limbic brain regions. CB1R-immunogold was
      principally localized to cytoplasmic endomembranes and synaptic or extrasynaptic
      plasma membranes of axonal profiles, but was also affiliated with postsynaptic
      membrane specializations in dendrites. The axonal profiles included many single
      CB1R-labeled axon terminals as well as terminals containing CB1R-immunogold and
      either Dyn or ME immunoreactivity. Dually labeled terminals comprised 26% of all
      Dyn- and 17% of all ME-labeled axon terminals. Both single- and dual-labeled
      terminals formed mainly inhibitory-type synapses, but almost 16% of these
      terminals formed excitatory synapses. Approximately 60% of the CB1R-labeled
      axonal profiles opposed or converged with axon terminals containing NAPE-PLD
      immunoreactivity. We conclude that CB1Rs in the mouse VP have subcellular
      distributions consistent with on demand activation by endocannabinoids that can
      regulate the release of functionally opposed opioid peptides and also modulate
      inhibitory and excitatory transmission.

PMID- 22863676
TI  - Superoxide anions modulate the effects of angiotensin-(1-7) in the rostral
      ventrolateral medulla on cardiac sympathetic afferent reflex and sympathetic
      activity in rats.
AB  - Both angiotensin (Ang)-(1-7) and Ang II in the rostral ventrolateral medulla
      (RVLM) increase renal sympathetic nerve activity (RSNA) and mean arterial
      pressure (MAP) and enhance the cardiac sympathetic afferent reflex (CSAR).
      NAD(P)H oxidase-derived superoxide anions in the RVLM mediate the effects of Ang
      II on CSAR and sympathetic activity. However, whether the superoxide anions
      mediate the effects of Ang-(1-7) in RVLM is still unclear. This study was
      designed to determine whether superoxide anions mediate the effects of Ang-(1-7)
      in the RVLM, including increasing the RSNA and MAP and enhancing the CSAR, and to
      determine whether NAD(P)H oxidase is the major origin of the superoxide anions in
      rats. RSNA and MAP were recorded in sinoaortic-denervated and cervical
      vagotomized rats with urethane and alpha-chloralose anesthesia. The CSAR was
      evaluated by the RSNA and MAP responses to the epicardial application of
      capsaicin. Bilateral RVLM microinjection of the superoxide anion scavengers
      tempol or tiron, or the NAD(P)H oxidase inhibitor apocynin inhibited the effects
      of Ang-(1-7) in RVLM, while the superoxide dismutase (SOD) inhibitor
      diethyldithiocarbamic acid (DETC) potentiated the effects of Ang-(1-7). Ang-(1-7)
      increased but Mas receptor antagonist D-Alanine-Ang-(1-7) (A-779) decreased the
      NAD(P)H oxidase activity and superoxide anion level in the RVLM. The Ang-(1-7)
      induced increases in NAD(P)H oxidase activity and superoxide anion level were
      abolished by pre-treating the RVLM with apocynin or A-779 but not the AT(1)
      receptor antagonist losartan. The epicardial application of capsaicin increased
      NAD(P)H oxidase activity and superoxide anion level; the effect was inhibited by
      A-779 and enhanced by Ang-(1-7). These results indicate that superoxide anions
      are involved in modulating the effects of Ang-(1-7) and Mas receptor in the RVLM:
      increasing the RSNA and MAP and enhancing the CSAR. The enzyme of NAD(P)H oxidase
      is a major source of the superoxide anions that modulate the effects of Ang-(1-7)
      in the RVLM.

PMID- 22863677
TI  - Muscarinic acetylcholine receptor-mediated effects in slices from human
      epileptogenic cortex.
AB  - Acetylcholine has been implicated in higher cortical functions such as learning,
      memory and cognition, yet the cellular effects of muscarinic acetylcholine
      receptor (mAChR) activation are poorly understood in the human cortex. Here we
      investigated the effect of the mAChR agonist carbachol (CCh) and various mAChR
      antagonists in human cortical slices (from tissue removed during neurosurgical
      treatment of epilepsy) by intracellular and extracellular recordings. CCh
      increased neuronal firing, which was antagonised by atropine (non-selective mAChR
      antagonist) and pirenzepine (M(1)/M(4) mAChRs antagonist) when applied before or
      after CCh application. AF-DX 116 (M(2)/M(4) mAChRs antagonist) had no effect on
      CCh-induced increase of firing. CCh also reduced evoked excitatory postsynaptic
      potentials (EPSP), and the CCh-induced depression of EPSP was fully reversed by
      atropine. Pirenzepine reversed the depression of CCh on EPSP, but failed to
      prevent the depression when applied before CCh. AF-DX 116 prevented the CCh
      induced depression of evoked EPSP when applied before CCh. CCh also depressed
      GABAergic transmission and this effect was antagonised by AF-DX 116. Xanomeline
      (M(1)/M(4) mAChR agonist) increased neuronal firing and decreased EPSP, but had
      no effect on GABAergic transmission. Reduction (with linopirdine) and enhancement
      (with retigabine) of the M-current (mediated by K(V)7 channels), increased and
      decreased neuronal firing, respectively, but had marginal effects on the evoked
      EPSP. Our results indicate that three pharmacologically distinct mAChRs modulate
      neuronal firing, glutamatergic and GABAergic transmissions in the human
      epileptogenic neocortex. The data are discussed towards possible implications of
      altered mAChR signalling in hyperexcitability and cognitive functions in the
      human neocortex.

PMID- 22863678
TI  - Sex differences in U50,488H-induced phosphorylation of p44/42 mitogen-activated
      protein kinase in the guinea pig brain.
AB  - Recently there has been a widespread interest in the development of kappa opioid
      receptor (KOPR) ligands for treatment of pain, depression and anxiety, and
      prevention of stress-induced drug relapse. However, most of these preclinical
      studies have been conducted using male experimental animals. In the present study
      we examined if sex differences exist in neural activity induced by the KOPR
      agonist trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)
      benzeneacetamide methanesulfonate (U50,488H). Here, we used immunohistochemistry
      to detect activation (phosphorylation) of p44/42 mitogen-activated protein kinase
      (MAPK) as an indicator of neural activity. Following habituation to injection for
      3 days, adult guinea pigs received a single injection of U50,488H (5mg/kg, s.c.)
      and perfused 30-45 min later. U50,488H-induced an increase in the number of cells
      immuno-positive for phosphorylated p44/42 MAPK in subregions of the amygdala,
      thalamus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and
      dorsal raphe nuclei. In contrast, U50,488H-induced a decrease in immuno-positive
      cells in the ventrolateral and lateral orbital cortex. Pretreatment with the KOPR
      antagonist norbinaltorphimine (10mg/kg, i.p.) 18 h prior to U50,488H
      significantly reversed the effects of U50,488H in most regions. In addition, we
      observed a notable sex difference in the basolateral amygdala; in males, U50,488H
      induced an increase in immuno-positive cell numbers but a decrease in females.
      However, across other brain regions males were generally more sensitive to
      U50,488H-induced alterations than females. These results suggest the need to
      include female subjects in studies examining emotional responses to KOPR ligands.

PMID- 22863679
TI  - F-spondin gene transfer improves memory performance and reduces amyloid-beta
      levels in mice.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia affecting the
      elderly. Evidence has emerged signifying that stimulation of the reelin pathway
      should promote neural plasticity and suppress molecular changes associated with
      AD, suggesting a potential therapeutic application to the disease. This was
      explored through the use of lentiviral vector-mediated overexpression of the
      reelin homolog, F-spondin, which is an activator of the reelin pathway.
      Intrahippocampal gene transfer of F-spondin improved spatial learning/memory in
      the Morris Water Maze and increased exploration of the novel object in the Novel
      Object Recognition test in wild-type mice. F-spondin overexpression also
      suppressed endogenous levels of amyloid beta (Abeta(42)) in these mice and
      reduced Abeta plaque deposition while improving synaptophysin expression in
      transgenic mouse models of AD. These data demonstrate pathologic and cognitive
      improvements in mice through F-spondin overexpression.

PMID- 22863681
TI  - IKey+: a new single-access key generation web service.
AB  - Single-access keys are a major tool for biologists who need to identify
      specimens. The construction process of these keys is particularly complex
      (especially if the input data set is large) so having an automatic single-access
      key generation tool is essential. As part of the European project ViBRANT, our
      aim was to develop such a tool as a web service, thus allowing end-users to
      integrate it directly into their workflow. IKey+generates single-access keys on
      demand, for single users or research institutions. It receives user input data
      (using the standard SDD format), accepts several key-generation parameters
      (affecting the key topology and representation), and supports several output
      formats. IKey+is freely available (sources and binary packages) at
      www.identificationkey.fr. Furthermore, it is deployed on our server and can be
      queried (for testing purposes) through a simple web client also available at
      www.identificationkey.fr (last accessed 13 August 2012). Finally, a client plugin
      will be integrated to the Scratchpads biodiversity networking tool
      (scratchpads.eu).

PMID- 22863682
TI  - Position-controlled functional oxide lateral heterostructures consisting of
      artificially aligned (Fe,Zn)3O4 nanodots and BiFeO3 matrix.
AB  - We demonstrate an advanced fabrication method for perfectly position-controlled
      ferromagnetic semiconductor (Fe,Zn)(3)O(4) nanodot arrays down to several hundred
      nanometers in size surrounded by a ferroelectric BiFeO(3) matrix. By performing
      position-selective crystal growth of perovskite BiFeO(3) on the position
      controlled epitaxial spinel (Fe,Zn)(3)O(4) nanodot-seeding template, which is
      prepared using a hollow molybdenum mask lift-off nanoimprint lithography process
      on a perovskite La-doped SrTiO(3)(001) substrate, we produce functional oxide
      three-dimensional lateral heterojunctions. The position-selectivity can be
      explained based on standard surface diffusion theory with a critical nucleation
      point. Establishing this fabrication process could lead to innovative
      nanointegration techniques for spintronic oxide materials.

PMID- 22863680
TI  - The protective effect of astrocyte-derived 14,15-epoxyeicosatrienoic acid on
      hydrogen peroxide-induced cell injury in astrocyte-dopaminergic neuronal cell
      line co-culture.
AB  - Astrocytes perform several functions that are essential for normal neuronal
      activity. They play a critical role in neuronal survival during ischemia and
      other degenerative injuries and also modulate neuronal recovery by influencing
      neurite outgrowth. In this study, we investigated the neuroprotective effects of
      astrocyte-derived 14,15-epoxyeicosatrienoic acid (14,15-EET), metabolite of
      arachidonic acid by cytochrome P450 epoxygenases (CYP), against oxidative stress
      induced by hydrogen peroxide (H(2)O(2)). We found that dopaminergic neuronal
      cells (N27 cell line) stimulated with two different doses of H(2)O(2) (0.1 and
      1mM) for 1h showed decreased cell viability compared to the control group, while
      astrocytes showed less cell death after stimulation with the same doses of
      H(2)O(2) for 1h. Dopaminergic neuronal cells (N27 cell line) pretreated with
      different doses of 14,15-EET (0.1-30 MUM, 30 min) before H(2)O(2) stimulation
      also showed increased cell viability. Furthermore, pre-treatment of the co
      cultured cells with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, an inhibitor of
      the EET metabolizing enzyme, soluble epoxide hydrolase (sEH), before H(2)O(2)
      stimulation (1mM, for 1h) increased cell viability. It also increased the
      endogenous level of 14,15-EET in the media compared to control group. However,
      pretreatment with the CYP epoxygenase inhibitor miconazole (1-20 MUM, 1h) before
      H(2)O(2) (1mM, 1h) stimulation showed decreased cell viability. Our data suggest
      that 14,15-EET which is released from astrocytes, enhances cell viability against
      oxidant-induced injury. Further understanding of the mechanism of 14,15-EET
      mediated protection in dopaminergic neurons is imperative, as it could lead to
      novel therapeutic approaches for treating CNS neuropathologies, such as
      Parkinson's disease.

PMID- 22863684
TI  - Bipolar irrigated radiofrequency ablation: a therapeutic option for refractory
      intramural atrial and ventricular tachycardia circuits.
AB  - BACKGROUND: Irrigated radiofrequency (RF) ablation can be insufficient to
      eliminate intramurally located septal atrial flutter (AFL) and ventricular
      tachycardia (VT) circuits. Bipolar ablation between 2 ablation catheters may be
      considered for such circuits. OBJECTIVE: To evaluate the utility of bipolar
      irrigated ablation to terminate arrhythmias resistant to unipolar ablation.
      METHODS: In vitro: Bipolar and sequential unipolar RF ablation lesions were
      placed on porcine ventricular tissue in a saline bath to assess for lesion
      transmurality. Clinical: 3 patients with atypical septal flutter (AFL), 4
      patients with septal VT, and 2 with left ventricle free-wall VT, all of whom
      failed sequential unipolar RF ablation, underwent bipolar RF ablation using
      irrigated catheters placed on either surface of the interatria/interventricular
      septum and left ventricle free-wall, respectively. RESULTS: In vitro: Bipolar RF
      was found to be more likely to achieve transmural lesions (82% vs 33%; P = .001)
      and could do so in tissues with thicknesses of up to 25 mm. Clinical: All 5 AFLs
      (3 patients) were successfully terminated with bipolar RF. In follow-up, AFL
      recurred in 2 of the 3 patients and atrial fibrillation and AFL recurred in 1 of
      the 3. All 3 thereafter underwent repeat procedures with successful maintenance
      of sinus rhythm in 2 of the 3 patients (6-month follow-up). In the VT subgroup, 5
      of 6 septal VTs and 2 of 3 free-wall VTs were terminated successfully during
      ablation. In follow-up (12 months), 2 of the 4 patients in the septal bipolar
      group and 1 of the 2 patients in the free-wall group remained free of VT.
      CONCLUSIONS: Bipolar RF can be used to terminate arrhythmias in select patients
      with tachyarrhythmias.

PMID- 22863683
TI  - Cytochrome P450 2S1 depletion enhances cell proliferation and migration in
      bronchial epithelial cells, in part, through modulation of prostaglandin E(2)
      synthesis.
AB  - Cytochromes P450 (P450s) contribute to the metabolic activation and inactivation
      of various endogenous substrates. Despite years of research, the physiological
      role of CYP2S1 remains unknown. CYP2S1 has demonstrated NADPH P450-reductase
      independent metabolism of cyclooxygenase (COX)-derived prostaglandins [e.g.,
      prostaglandin G(2) (PGG(2))] at nanomolar concentrations. Arachidonic acid is
      converted to prostaglandin precursors [PGG(2) and prostaglandin H(2) (PGH(2))]
      through COX. These precursors are used to synthesize numerous prostanoids,
      including PGE(2). Prostaglandin E(2) (PGE(2)) promotes cell proliferation and
      cell migration and inhibits apoptosis. CYP2S1 metabolism of PGG(2) presumably
      sequesters PGG(2) and PGH(2), making them unavailable for synthesis of
      prostanoids such as PGE(2). Whether CYP2S1 contributes to prostaglandin
      metabolism and influences cell physiological remains to be determined. The
      purpose of this study was to evaluate the physiological role of CYP2S1, if any,
      in human bronchial epithelial cells [SV40-derived bronchial epithelial cell line
      (BEAS-2B)]. To do this, we used small interfering RNA to deplete CYP2S1 mRNA and
      protein by approximately 75% and evaluated the impact of CYP2S1 depletion on cell
      proliferation and migration. CYP2S1 depletion enhanced both cell proliferation
      and migration in BEAS-2B cells. Consistent with the proposed role of CYP2S1 in
      PGE(2) synthesis, the reduction in CYP2S1 expression doubled intracellular PGE(2)
      levels. Pharmacological administration of PGE(2) enhanced cell proliferation in
      BEAS-2B cells but failed to promote migration. Our data reveal an important role
      for CYP2S1 in the regulation of cell proliferation and migration, occurring in
      part through modulation of prostaglandin synthesis.

PMID- 22863685
TI  - Atrial fibrillation and the risk of incident dementia: a meta-analysis.
AB  - BACKGROUND: The risk of cerebrovascular embolic events with atrial fibrillation
      (AF) is potentially linked to an increased risk of cognitive decline and
      dementia. However, epidemiologic studies exploring the association between AF and
      incident dementia have reported conflicting results. OBJECTIVE: The purpose of
      this study was to perform a meta-analysis of observational studies specifically
      designed to evaluate the prospective relationship between AF and incident
      dementia. METHODS: We searched PubMed, CENTRAL, BioMedCentral, Embase,
      Cardiosource, clinicaltrials.gov, and ISI Web of Science (January 1980 to May
      2012). No language restriction was applied. Two independent reviewers screened
      titles and abstracts to identify population-based studies that prospectively
      evaluated the association between AF and the incidence of dementia in patients
      not suffering an acute stroke and with normal cognitive function at baseline,
      providing the hazard ratio (HR) obtained in multiple Cox regression analyses, and
      adjusted for all confounding variables. Two independent reviewers assessed risk
      of bias according to the Cochrane Collaboration, and extracted patient and study
      characteristics and the adjusted HR of incident dementia with its 95% confidence
      interval (CI) of patients with AF vs those without AF. RESULTS: Eight studies
      with 77,668 patients were included in the analysis. All studies had a prospective
      observational design and included elderly patients (mean age range 61-84 years)
      with normal cognitive function at baseline, of whom 11,700 (15%) had AF. After a
      mean follow-up of 7.7 +/- 9.1 years (range 1.8-30 years), 4773 of 73,321 (6.5%)
      patients developed dementia. Two studies did not report the rates of dementia at
      follow-up but reported the adjusted HR and were included in the pooled analysis.
      At pooled analysis adjusted for baseline confounders and covariates, AF was
      independently associated with increased risk of incident dementia (HR = 1.42 [95%
      CI 1.17-1.72], P <.001). CONCLUSION: AF is independently associated with
      increased risk of dementia. Patients with AF should be periodically screened for
      dementia, which should be included among the outcomes assessed in AF treatment
      trials.

PMID- 22863686
TI  - Concurrent orthopedic and neurosurgical procedures in pediatric patients with
      spinal deformity.
AB  - The management of pediatric patients with complex spinal deformity often requires
      both an orthopedic and a neurosurgical intervention. The reasons for multiple
      subspecialty involvement include, but are not limited to, the presence of a
      tethered cord requiring release or a syrinx requiring decompression. It has been
      common practice to perform these procedures in a staged manner, although there is
      little evidence in the literature to support separate interventions. We reviewed
      a series of consecutive patients who underwent spinal deformity correction and a
      neurosurgical intervention concurrently in an attempt to assess the safety,
      efficacy, and possible complications associated with such an approach. Eleven
      patients were reviewed who underwent concurrent orthopedic and neurosurgical
      procedures. Data were collected for patient demographics, preoperative diagnosis,
      procedures performed, intraoperative and perioperative complications, as well as
      any unexpected return to the operating room for any reason. Operative notes and
      anesthesia records were reviewed to determine estimated blood loss, surgical
      time, and the use of intraoperative neurological monitoring. Patient diagnoses
      included myelodysplasia (N=6), congenital scoliosis and/or kyphosis (N=4), and
      scoliosis associated with Noonan syndrome (N=1). Age at the time of surgery
      averaged 9 years 2 months (range=14 months to 17 years 2 months). Estimated blood
      loss averaged 605 ml (range=50-3000 ml). The operative time averaged 313 min
      (range=157-477 min). There were no intraoperative complications, including
      incidental dural tears or deterioration in preoperative neurological status. One
      patient developed a sore associated with postoperative cast immobilization that
      led to a deep wound infection. It appears that concurrent orthopedic and
      neurosurgical procedures in pediatric patients with significant spinal
      deformities can be performed safely and with minimal intraoperative and
      postoperative complications when utilizing modern surgical and neuromonitoring
      techniques. Level of evidence=Level IV.

PMID- 22863687
TI  - High-grade spondyloretrolisthesis in a 12-year-old girl with neurofibromatosis
      type 1:  a case report and literature review.
AB  - Neurofibromatosis (NF) type 1 is characterized by several skin, endocrine,
      central nervous system and musculoskeletal manifestations, spine deformities
      being the most common, affecting up to 64% of patients. Thoracic kyphoscoliosis
      is the most common deformity observed; however, high-grade spondylolisthesis and
      dural defects such as dural ectasia can also be found. The aim of this study is
      to describe a case of high-grade spondyloretrolisthesis in an NF-1 patient,
      associated with dural ectasia and extensive lumbar laminectomies, and to discuss
      our management and review the current literature on this controversial topic. A
      12-year-old girl with NF-1 who had undergone extensive lumbar laminectomies in an
      outside facility presented to our emergency department complaining of back pain
      and lower limbs upper motor neuron symptoms. Image studies showed a high-grade
      lumbar spondyloretrolisthesis associated with dural ectasia. The first step of
      treatment was spine immobilization using a Boston brace. An anterior approach was
      used, and an L2 corporectomy was performed, using a Moss type cage between L1 and
      L3 with an instrumented arthrodesis and autologous bone graft for stabilization
      purposes. The second step planned was a posterior approach for arthrodesis and
      instrumentation, but after an extensive discussion with the parents and the
      patient, the parents did not agree to the procedure planned for the patient. A
      brace was used for 1 year while rehabilitation was performed. At the 1-year
      follow-up, there was a 70 degrees  kyphosis at the thoracolumbar junction but it
      was clinically stable, with an acceptable sagittal balance. Dural ectasia is not
      a common finding in children with NF-1; however, it should be identified as its
      presence may predispose to spine instability and as a consequence the development
      of a high-grade spondyloretrolisthesis. Even though a few cases have been
      reported, we believe that it is important to consider the option of a double
      approach to achieve a better correction in both planes and a good outcome. If an
      extensive laminectomy is involved, it is mandatory to perform a posterior fusion
      and instrumentation.

PMID- 22863688
TI  - The psychosocial impact of an infantile haemangioma on children and their
      parents.
AB  - Infantile haemangiomas (IHs) are common, benign vascular tumours in children that
      appear soon after birth and regress before the age of 12 years. Physicians have
      always been concerned about the considerable psychosocial impact these lesions
      might have on children and their parents. This is the first critical review of
      studies on the psychosocial impact of IHs on children and their families. Future
      directions for research are suggested. As propranolol is becoming the most common
      first choice treatment for IHs, this article discusses its use in the light of
      this review.

PMID- 22863689
TI  - Vitamin D in children with cystic fibrosis.
AB  - PURPOSE: The Cystic Fibrosis Trust in 2007 published a recommended target of 75
      150 nmol/L for 25-hydroxyvitamin D (25-OHD). In 2008 we found that only 10% of
      pancreatic insufficient (PI) children met this target. An increase in
      supplementation was implemented and a repeat audit performed in 2010. METHODS: PI
      children >=1 year under sole-care in our regional centre were included. Vitamin
      D3 supplementation increased by >450% to either 3800 IU/day liquid or 800 IU
      daily plus 20,000 IU weekly tablets. In 2010 pancreatic sufficient (PS) children
      were also audited separately. RESULTS: The median 25-OHD level increased from
      51.5 nmol/L in 2008 (n=78, 10% >75 nmol/L) to 72 nmol/L in 2010 (n=72, 51% >75
      nmol/L), p<0.0001. In PS children (n=15 in 2010) 87% had 25-OHD levels <75
      nmol/L. CONCLUSIONS: A substantial increase in supplementation led to a
      significant increase in 25-OHD levels but around half still failed to reach the
      recommended target.

PMID- 22863690
TI  - Long-term follow-up of contacts exposed to multidrug-resistant tuberculosis in
      Victoria, Australia, 1995-2010.
AB  - SETTING: The effectiveness of public health strategies following exposure to
      multidrug-resistant tuberculosis (MDR-TB) is not clear. OBJECTIVE: To perform
      long-term follow-up of MDR-TB contacts and review individual outcomes and
      management approaches. DESIGN: Retrospective review  of MDR-TB contacts
      identified by the Victorian Department of Health from 1995 to 2010. Health
      records, including personal medical and pharmacy records and statewide clinical
      and laboratory TB databases, were searched to identify management strategies and
      individual outcomes. RESULTS: A  total of 570 contacts of 47 MDR-TB cases were
      identified, with a total follow-up period of 3093 person-years of observation
      (PYO) since exposure. Of 570 contacts, 49 (8.6%) were considered likely to have
      been infected with Mycobacterium tuberculosis from index cases, and 11/49 (22.5%)
      of these were prescribed preventive therapy tailored to isolate susceptibility.
      No MDR-TB cases occurred in those receiving preventive treatment, while two cases
      were observed in those not treated (incidence 2878/100 000 PYO during the first 2
      years post exposure). CONCLUSIONS: The  risk of MDR-TB transmission to close
      contacts in this low-prevalence setting highlights the potential for public
      health strategies involving preventive treatment.

PMID- 22863691
TI  - Nontraumatic amputation: incidence and cost analysis.
AB  - Lower extremity amputation (LEA) is devastating for those affected and a
      significant factor in health care costs. Although the overall incidence of
      amputation has been declining, the decline is not universal. The objectives of
      this study were to identify patients with nontraumatic amputation at Harbor-UCLA
      Medical Center (HUMC) from January 2000 to January 2007, to calculate their 1
      year and 5-year mortality rates after amputation and to estimate the financial
      cost of those amputations. The authors searched the HUMC electronic database by
      ICD codes (84.10-84.18) to identify patients with LEA and subsequently searched
      the National Death Index database for deaths in study subjects to calculate
      mortality rates. HUMC is a Los Angeles County tertiary teaching medical center
      that provides medical care to a large percentage of the Los Angeles County
      population, especially those without health insurance. There were 1169 admissions
      in 847 patients with nontraumatic LEA with a 1-year mortality rate of 9.1% and 5
      year mortality rate of 25.6%. Only major amputation and increasing age were
      independent risk factors for 1-year mortality rate. At 1 year, the re-amputation
      rate for nontraumatic LEA was 26.7%. African American and Hispanic females had a
      significantly higher percentage of major amputations than corresponding males and
      white females. The average length of hospital stay was more than double for
      patients with nontraumatic amputation than for all other admissions (12.7 vs 5.3
      days). There were 14,846 hospital days for 1169 nontraumatic amputation
      admissions with an estimated cost of $47,033,767. Amputation remains common at
      HUMC and the associated mortality rates and economic costs are high. In the
      authors' opinion, a coordinated and serious campaign by all involved in the
      health care system is urgently needed to implement proven and effective measures
      such as establishing multidisciplinary foot care clinics to reduce amputation.

PMID- 22863692
TI  - A rare case of diabetic hand ulcer caused by Streptococcus agalactiae.
AB  - This study reports the case of a 71-year-old woman with type 2 diabetes whose
      paronychia rapidly progressed to the right middle finger and then to the whole
      dorsal aspect necrosis of the right hand. After admission, the diagnosis of
      diabetic hand ulcer was established and Streptococcus agalactiae found as the
      pathogen. The authors controlled glucose, used 3% hydrogen peroxide and
      sulfadiazine silver in routine dressing, as well as surgical debridement, topical
      negative pressure, and skin grafting. The wound closed in 32 days after surgery.
      Diabetic hand ulcer is often developed from a small wound. The wound, if
      neglected, will expand very quickly and may lead to amputation and even death. So
      early diagnosis, standardized treatment, and postoperative rehabilitation is very
      important.

PMID- 22863694
TI  - An overview on chemical derivatization and stability aspects of selected
      avermectin derivatives.
AB  - Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide
      compounds, well-known for their novel mode of action against a broad range of
      nematode and anthropod animal parasites. In this review, chemical and
      pharmaceutical aspects of AVM derivatives are described including stability,
      synthetic and purification processes, impurities and degradation pathways, and
      subsequent suggestions are made to improve the chemical stability. It has been
      found out that unique structure of AVM molecules and presence of labile groups
      facilitated the derivatization of AVM into various compounds showing strong
      anthelmintic activity. However, the same unique structure is also responsible for
      labile nature related to sensitive stability profile of molecules. AVMs are found
      to be unstable in acidic and alkaline conditions. In addition, these compounds
      are sensitive to strong light, and subsequently presence of photo-isomer in
      animals treated topically with AVM product is well known. The pharmacoepial
      recommendations for addition of antioxidant into drug substance, as well as its
      products, arises from the fact that AVM are very sensitive to oxidation.
      Formations of solvates, salts, epoxides, reduction of double bonds and developing
      liquid formulation around pH 6.2, were some chemical approaches used to retard
      the degradation in AVM. This coherent review will contribute towards the better
      understanding of the correlation of chemical processes, stability profile and
      biological activity; therefore, it will help to design the shelf-life stable
      formulations containing AVMs.

PMID- 22863693
TI  - Investigating metabotropic glutamate receptor 5 allosteric modulator
      cooperativity, affinity, and agonism: enriching structure-function studies and
      structure-activity relationships.
AB  - Drug discovery programs increasingly are focusing on allosteric modulators as a
      means to modify the activity of G protein-coupled receptor (GPCR) targets.
      Allosteric binding sites are topographically distinct from the endogenous ligand
      (orthosteric) binding site, which allows for co-occupation of a single receptor
      with the endogenous ligand and an allosteric modulator that can alter receptor
      pharmacological characteristics. Negative allosteric modulators (NAMs) inhibit
      and positive allosteric modulators (PAMs) enhance the affinity and/or efficacy of
      orthosteric agonists. Established approaches for estimation of affinity and
      efficacy values for orthosteric ligands are not appropriate for allosteric
      modulators, and this presents challenges for fully understanding the actions of
      novel modulators of GPCRs. Metabotropic glutamate receptor 5 (mGlu(5)) is a
      family C GPCR for which a large array of allosteric modulators have been
      identified. We took advantage of the many tools for probing allosteric sites on
      mGlu(5) to validate an operational model of allosterism that allows quantitative
      estimation of modulator affinity and cooperativity values. Affinity estimates
      derived from functional assays fit well with affinities measured in radioligand
      binding experiments for both PAMs and NAMs with diverse chemical scaffolds and
      varying degrees of cooperativity. We observed modulation bias for PAMs when we
      compared mGlu(5)-mediated Ca(2+) mobilization and extracellular signal-regulated
      kinase 1/2 phosphorylation data. Furthermore, we used this model to quantify the
      effects of mutations that reduce binding or potentiation by PAMs. This model can
      be applied to PAM and NAM potency curves in combination with maximal fold-shift
      data to derive reliable estimates of modulator affinities.

PMID- 22863695
TI  - Essential structure of opioid kappa receptor agonist nalfurafine for binding to
      kappa receptor 1: synthesis of decahydroisoquinoline derivatives and their
      pharmacologies.
AB  - On the basis of the three-dimensional pharmacophore model of opioid kappa
      agonists, we simplified the structure of nalfurafine (selective kappa agonist) to
      find the essential structural moieties for binding the opioid receptors,
      especially kappa receptor type. As a result, we found that the trans-fused
      decahydroisoquinoline derivatives without a phenol ring bound the opioid receptor
      in micromolar order and that both the amide side chain and the nitrogen
      substituted by the cyclopropylmethyl group were indispensable moieties for
      eliciting the kappa selectivity. The simple decahydroisoquinoline without amide
      side chain also bound the opioid receptor without receptor type selectivity,
      suggesting that the message-address concept would be applicable to even these
      simple derivatives. These findings that the simple decahydroisoquinoline
      derivatives showed the affinities for the opioid receptors, especially some of
      the compounds showed kappa selectivity, are the first example in the opioid
      field.

PMID- 22863696
TI  - Factors affecting the bitterness intensities of ten commercial formulations of
      ambroxol.
AB  - The bitterness of 10 different products with ambroxol as active ingredient, the
      original and nine generics, were evaluated by human gustatory sensation tests in
      which the tablets were kept in the mouth, with water, at 20 and 37 degrees C. The
      products all showed different bitterness intensities. The original and some of
      the generic products had comparatively low bitterness intensities but some of the
      generic products had comparatively high bitterness intensities. The bitterness
      intensities of these 10 was found to be significantly correlated with both the
      disintegration time, as evaluated using the ODT-101 (a recently developed
      apparatus), and the drug concentration in dissolved medium, as measured in a
      conventional dissolution test. The bitterness threshold of ambroxol solution was
      found to increase when the temperature of the water with which the tablets were
      taken, was raised from 20 to 37 degrees C. The equation was calculated to predict
      the bitterness intensity of ambroxol, a function based on temperature and the
      ambroxol concentration using data from a standard ambroxol solution at 4, 20 and
      37 degrees C. The bitterness intensities obtained for the 10 ambroxol
      formulations with water at 20 and 37 degrees C, coincided with the bitterness
      values predicted by the equation.

PMID- 22863697
TI  - Cytotoxic terpenes from the stems of Dipterocarpus obtusifolius collected in
      Cambodia.
AB  - From the stems of Dipterocarpus obtusifolius, five new triterpenes, 3-oxo-20
      hydroxy-30alpha-methyl,17(29)alpha-epoxy-28-norlupane (1), 3-oxo-20-hydroxy
      30beta-methyl-17(29)alpha-epoxy-28-norlupane (2), 3,20-dioxo-28,29-norlupan
      17alpha-ol (3), 27-demethyl-20(S)-dammar-23-ene-20-ol-3,25-dione (4), and 3-epi
      cecropic acid (5) together with 13 known compounds including diterpene,
      sesquiterpenes and triterpenes were isolated and characterized. All isolates were
      tested for their cytotoxicities against a small panel of human cancer cell lines.
      Of the tested compounds, compounds 4-11 were found to be cytotoxic against one or
      more human cancer cell lines.

PMID- 22863698
TI  - Personal and atmospheric concentrations of ozone in southeastern Hyogo
      prefecture, Japan.
AB  - Twenty-one data sets composed of readings collected by atmospheric ozone monitors
      worn by individuals on their clothing and installed outside their home or office
      were collected using Ogawa passive ozone samplers in southeastern Hyogo
      prefecture, Japan from September 12 to 13, 2011. The concentrations of personal
      and outdoor ozone ranged from not detectable to 23.2 ppb and from 4.7 to 38.3
      ppb, respectively. The mean concentration of personal exposure to ozone was 3.7
      ppb and was significantly lower than that of outdoor ozone (18.5 ppb). This
      suggests that the concentrations of outdoor ozone affect personal ozone exposure.
      However, in this study, we found no correlation between the concentrations of
      personal ozone and the total time spent outdoors or the time of day the
      individual was outside. In contrast, the mean concentrations of outdoor ozone
      were similar to those of ozone measured at the 12 nearest Ambient Monitoring
      Stations (AMSs). However, when the AMS was situated near a main road, the
      regional ozone levels were underestimated.

PMID- 22863699
TI  - Comparison of particle size and dispersion state among commercial cyclosporine
      formulations and their effects on pharmacokinetics in rats.
AB  - Generic versions of Neoral, a microemulsion capsule formulation of cyclosporine,
      have been approved worldwide. However, there are concerns about the quality and
      efficacy of the generics due to the formulation specificity and differences in
      inactive ingredients among products. In this study, we measured the
      physicochemical properties of both the innovator and the generic formulations,
      and compared their bioavailability in rats. When the capsule contents were
      dispersed in water, the absorbance (600 nm wavelength) of generic products was
      higher than that of the innovator. Whereas the dispersion solution of the
      innovator in Fed State Simulated Intestinal Fluid was nearly clear, that of all
      the generics became white and turbid. The mean diameter of the microemulsion (or
      emulsion) formed in water by the generics was 39.7, 57.7, 64.5, and 74.8 nm, all
      of which were larger than that of the innovator (26.4 nm). Although the T(max) of
      the generics tended to be long relative to that of the innovator, there were no
      significant differences between the innovator and generics with regard to maximum
      blood concentration (C(max)) or area under the curve (AUC). These results suggest
      that the physicochemical differences between the innovator and the generics will
      not have a significant effect on C(max) or AUC, which is necessary to ensure
      bioequivalence.

PMID- 22863700
TI  - Taste masking of propiverine hydrochloride by conversion to its free base.
AB  - The aim of the present study was to mask the bitterness of propiverine
      hydrochloride (P-4) by converting it to propiverine free base. Fine granules
      comprising the free base, which was converted from P-4 by desalination, were
      prepared. By using Fourier transform infrared spectroscopy, thermogravimetry
      differential thermal analysis, and powder X-ray diffraction spectra, we confirmed
      that P-4 had been converted into propiverine free base by desalination during the
      manufacturing process. Furthermore, the conversion into free base appeared to
      result in decreased solubility, and both the taste testing sensor and tasting
      volunteers determined that it masked the bitterness of P-4. On using the
      gustatory sensation test, the bitterness of the P-4 fine granules was confirmed
      to be weakened. The dissolution rate and bioavailability of fine granules of the
      free base were compared with tablets of P-4. The dissolution rate and
      bioavailability of the fine granules and tablets were almost the same. We
      successfully masked the taste of P-4 by converting it into free base using a
      manufacturing process that was suitable for commercial manufacturing.

PMID- 22863701
TI  - Characteristics of granular boehmite and its ability to adsorb phosphate from
      aqueous solution.
AB  - In this study, we investigated the surface properties of granulated boehmite with
      vinyl acetate (G-BE20) and measured the amount of phosphate it adsorbed and the
      effect of contact time and solution pH on the adsorption process. The specific
      surface area (144.9 m(2)/g) and the number of surface hydroxyl groups (0.88
      mmol/g) of G-BE20 were smaller than those of virgin boehmite (BE), which gave a
      specific surface area and number of surface hydroxyl groups of 297.0 m(2)/g and
      1.08 mmol/g, respectively. The amount of phosphate adsorbed increased with the
      temperature. The isotherm model of Langmuir was used to fit experimental
      adsorption equilibrium data for phosphate adsorption onto G-BE20. The calculated
      thermodynamic parameters show the spontaneous and endothermic nature of the
      adsorption process. The equilibrium adsorption onto G-BE20 was reached within 16
      h and the amount of phosphate adsorbed was 8.4 mg/g. The kinetic mechanism of
      phosphate uptake was evaluated with two different models: the Largergren pseudo
      first- and pseudo second-order models. The data obtained showed a better fit to
      the pseudo second-order model (0.991) than to the pseudo first-order model
      (0.967), as indicated by the r values. The rate constants for the adsorption of
      phosphate onto G-BE20 were calculated as 0.481 1/h and 0.029 g/mg h. The
      adsorption of phosphate onto G-BE20 was the maximum in the pH range 3.0-4.0.

PMID- 22863702
TI  - Distribution of polyphenols and a surfactant component in skin during Aerosol OT
      microemulsion-enhanced intradermal delivery.
AB  - As for most other polyphenols, intradermal delivery of curcumin and resveratrol
      is limited; however, it was significantly improved by a microemulsion using
      Aerosol OT (Aerosol OT microemulsion) and Tween 80 (Tween 80 microemulsion) as
      surfactants. Aerosol OT microemulsion was more effective and the incorporation
      ratio of these polyphenols into skin by Aerosol OT microemulsion was five-fold or
      ten-fold that by Tween 80 microemulsion. To clarify the mechanism of the
      enhancement we examined the distribution of these polyphenols and the surfactant
      component, Aerosol OT, using excised guinea pig skin and Yucatan micropig (YMP)
      skin. During permeation, polyphenols distributed deep in the skin. In particular,
      a small molecule, resveratrol, was mainly present in the dermis in YMP skin.
      Aerosol OT also distributed deep in the skin. These findings suggest the possible
      involvement of the interaction of surfactant molecules with skin components in
      the enhanced delivery process of polyphenols. The distribution ratio between the
      dermis and epidermis of the polyphenols, including quercetin, in the presence of
      Aerosol OT microemulsion decreased with the increase of molecular weight in YMP
      skin, suggesting the possibility that distribution to the dermis is regulated by
      the molecular size.

PMID- 22863703
TI  - Solid state characterizations and analysis of stability in azelnidipine
      polymorphs.
AB  - Azelnidipine, a new dihydropyridine calcium ion antagonist, was protected by
      patent in Japan. In present study, identifications of the crystal phases,
      including two polymorphic and a pseudopolymorphic crystal forms of azelnidipine,
      were attempted using powder X-ray diffraction (PXRD), differential scanning
      calorimetry (DSC), IR-, Raman-, THz-, and ss-NMR-spectroscopy. PXRD identified
      three different crystal forms, while, spectroscopy analysis provided the
      information of crystal structure involving intermolecular interactions. The
      transition thermodynamics of the azelnidipine polymorphs were extensively
      investigated by solubility method. The solubility of the two polymorphs of alpha
      and beta in 50% ethanol at 25, 31, 37, 42, and 49 degrees C was investigated; the
      values obtained were used to calculate the thermodynamic parameters of the
      transition reaction. The temperature of polymorphic phase transition in 50%
      ethanol was 50.78 degrees C, and the values of DeltaG(alpha,beta)(theta),
      DeltaH(alpha,beta)(theta), and DeltaS(alpha,beta)(theta) at 25 degrees C were 
      1.18 kJ.mol(-1), -14.81 kJ.mol(-1), and -45.73 J.mol(-1).K(-1), respectively.
      Form beta was proved to be thermodynamic stable form at room temperature and
      enantiotropically related with form alpha. The kinetics of the solid-state
      decomposition, studied using DSC analysis, showed that the activation energies of
      decomposition of the polymorphs alpha and beta at high temperatures were 148.67
      and 151.93 kJ.mol(-1).

PMID- 22863704
TI  - Relationship of chemical structure to in vitro anti-inflammatory activity of
      tirucallane triterpenoids from the stem barks of Aphanamixis grandifolia.
AB  - A series of tirucallane triterpenoids isolated from the stem barks of Aphanamixis
      grandifolia were assessed for their anti-inflammatory activity, exhibiting from
      weak to strong anti-inflammatory activity, by testing their inhibitory effects on
      nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-alpha) level in
      lipopolysaccharide (LPS) induced RAW264.7 murine macrophages. To explore the
      relationship between the structures and anti-inflammatory activity, a vast pool
      of molecular descriptors for each isolate were calculated. Genetic algorithms
      (GA) or simulated annealing (SA) based partial least squares (GA-PLS and SA-PLS)
      algorithms identified some important descriptor combinations, which were
      correlated with both sets of the anti-inflammatory data by partial least squares
      2 (PLS2) method. S-Plot was used to visualize the descriptor influence in the
      PLS2 model, disclosed five most important molecular descriptors, nOHt, RDF150m,
      lip_violation, Mor32m and JhetZ.

PMID- 22863705
TI  - Triterpene saponins from Pleurospermum kamtschaticum and their biological
      activity.
AB  - Eleven new triterpene saponins (1-11), together with fourteen known triterpene
      and triterpene saponins (12-25) were isolated from a MeOH extract of
      Pleurospermum kamtschaticum HOFFMANN (Umbelliferae). The chemical structures of
      the new compounds (1-11) were determined by means of MS, (1)H-NMR, (13)C-NMR,
      correlated spectroscopy (COSY), heteronuclear multiple bond correlation (HMBC),
      total correlated spectroscopy (TOCSY) and nuclear Overhauser effect spectroscopy
      (NOESY) to be pleurosaponin A (1)-K (11). The isolated compounds were tested for
      their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2,
      HCT15) in vitro using the sulforhodamine B bioassay (SRB) assay. All compounds
      showed little cytotoxicity against tested cell lines (IC(50) >30 uM).

PMID- 22863706
TI  - Dapson in heterocyclic chemistry, part V: synthesis, molecular docking and
      anticancer activity of some novel sulfonylbiscompounds carrying biologically
      active dihydropyridine, dihydroisoquinoline, 1,3-dithiolan, 1,3-dithian,
      acrylamide, pyrazole, pyrazolopyrimidine and benzochromenemoieties.
AB  - N,N'-(4,4'-Sulfonylbis(4,1-phenylene))bis(2-cyanoacetamid) 2 was utilized as a
      key intermediate for the synthesis of novel dihydropyridines 3, 4, 8,
      dihydroisoquinolines 5-7, dithiolan 10, dithian 11, acrylamide 12, benzochromenes
      17 and 18 and chromenopyridones 19 and 20. Compound 2 was the starting material
      in the synthesis of the acrylamide derivative 14, the pyrazole derivative 15 and
      the pyrazolopyrimidine derivative 16. All the synthesized compounds were
      evaluated for their in vitro anticancer activity against human breast cancer cell
      line (MCF7). Compound 19 showed the best cytotoxic activity with IC(50) value
      19.36 uM. In addition, molecular docking study of the synthesized compounds on
      the active sites of farnesyltransferase and arginine methyltransferase was
      performed in order to give a suggestion about the mechanism of action of their
      cytotoxic activity.

PMID- 22863707
TI  - Alkylphenols from the roots of Ardisia brevicaulis induce G1 arrest and apoptosis
      through endoplasmic reticulum stress pathway in human non-small-cell lung cancer
      cells.
AB  - From the roots of Ardisia brevicaulis DIELS, two new alkylphenol derivatives,
      named ardisiphenol E (2) and F (3), have been isolated together with a known
      alkylphenol, ardisiphenol D (1). The structures of 1-3 were elucidated by
      chemical and spectroscopic techniques. Compounds 1 and 2 exhibited strong
      cytotoxicities on two human non-small-cell lung cancer cell lines (H1299 and
      A549). We found that compounds 1 and 2 upregulated mRNA and protein expressions
      of endoplasmic reticulum (ER) stress markers including C/EBP homologous protein
      (CHOP), binding immunoglobulin protein (Bip) and inositol-requiring enzyme 1
      (IRE1) indicating 1 and 2 are novel natural ER stress inducers. Treatments with 1
      and 5 uM of 1 or 2 triggered G1 arrest in H1299 and A549 cells with concomitant
      downregulation of ubiquitin fusion degradation protein 1 (Ufd1) and S-phase
      kinase-associated protein 2 (Skp2) proteins and the accumulation of p27, the key
      axes of ER stress-mediated G1 arrest. Compounds 1 and 2 also induced apoptosis at
      high concentrations (10, 20 uM) which was shown to be coupled with the
      upregulation of CHOP and Bim, the activation of caspase-9, caspase-3 and poly(ADP
      ribose) polymerase (PARP) cleavage. These results indicate that compounds 1 and 2
      induce ER stress that subsequently causes G1 arrest and apoptosis in human non
      small-cell lung cancer cells and they may have potential anticancer effects.

PMID- 22863708
TI  - Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]pyrimidine
      derivatives bearing arylmethylene hydrazine moiety.
AB  - Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing
      arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and
      their chemical structures as well as the relative stereochemistry were confirmed.
      The synthesized compounds were evaluated for their cytotoxicity against three
      cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to
      significant cytotoxicity and high-selectivity against one or more cell lines,
      especially compounds 11c, 13b, 15f and 15g possessing dramatically increased
      cytotoxicity as compared with the positive controls, which were further evaluated
      for six other cancer cell lines and one normal cell line. The most promising
      compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable
      cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC(50)values of
      0.003 uM, 0.42 uM and 0.74 uM, which was 1.6- to 290-fold more potent than GDC
      0941.

PMID- 22863709
TI  - Design, synthesis and anticancer activities of diaryl urea derivatives bearing N
      acylhydrazone moiety.
AB  - A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were
      designed and synthesized. All the target compounds were evaluated for their
      cytotoxic activities in vitro against human lung adenocarcinoma epithelial cell
      line (A549), human breast cancer cell line (MDA-MB-231) and human leukemia cell
      line (HL-60) by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Several compounds (1a, 1f and 1h) were further evaluated
      against human embryonic fibroblast, lung-derived cell line (WI38). The
      pharmacological results indicated that some compounds exhibited promising
      anticancer activities. In particular, compound 1f showed the most potent
      cytotoxicity against the tested three cell lines with IC(50) values of 0.41 uM,
      0.24 uM and 0.23 uM, respectively.

PMID- 22863710
TI  - Photoinduced upregulation of calcitonin gene-related peptide in A549 cells
      through HNO release from a hydrophilic photocontrollable HNO donor.
AB  - Nitroxyl (HNO), a one-electron-reduced form of nitric oxide, has various
      biological activities, including a cardioprotective effect. Here, we first
      synthesized another, more hydrophilic photocontrollable HNO donor (3), which can
      release HNO in a spatially and temporally controlled manner, and then examined
      the properties of our series of compounds as practical HNO donors in a cellular
      system under photocontrol. We selected compound 2 as the preferred donor, and
      used it to show that calcitonin gene-related peptide (CGRP) can be upregulated in
      A549 cells via photocontrolled HNO release. This result demonstrates the
      suitability of this photocontrollable HNO donor for biological investigations.

PMID- 22863711
TI  - Synthesis of novel tetrahydro-1H-pyrazolo[4,3-c]pyridines via intramolecular
      nitrilimine cycloaddition.
AB  - The preparation of novel tetrahydro-1H-pyrazolo[4,3-c]pyridines is reported.
      Pivotal to the synthesis of these compounds was the development of mild reaction
      conditions to generate a highly functionalized nitrilimine capable of undergoing
      an intramolecular cycloaddition with a tethered alkyne. The desired cycloadduct
      was formed as an equal mixture of diastereomers.

PMID- 22863712
TI  - Disesquiterpenoid and sesquiterpenes from the flos of Chrysanthemum indicum.
AB  - One new disesquiterpenoid (1), two new sesquiterpenoids (2, 3), were isolated
      from the dry flos of Chrysanthemum indicum. The structures were elucidated by
      spectroscopic analysis, the absolute configurations of 1 and 3, were determined
      by single X-ray diffraction study.

PMID- 22863713
TI  - A new sphingolipid and furanocoumarins with antimicrobial activity from Ficus
      exasperata.
AB  - From the methanol extract of the stem bark of Ficus exasperata, a new
      sphingolipid named Ficusamide, (2S,3S,4R,11E)-2-[(2',3'
      dihydroxyhexacosanoylamino)]-11-octadecene-1,3,4-triol (1), along with three
      known furanocoumarins, (S)-(-) oxypeucedanin hydrate (2), (R)-(+) oxypeucedanin
      hydrate (3), bergapten (5-methoxypsoralen) and six other known compounds, were
      isolated. Their structures were characterized basing on spectroscopic methods and
      chemical evidence. Compounds (1-3) were analyzed for their antimicrobial
      activity. Ficusamide (1) showed wick activity (minimal inhibitory concentration
      (MIC)=312.5 ug/mL) against Escherichia coli, while the furanocoumarins (2) and
      (3) showed significant activity (MIC=9.76 ug/mL) against Bacillus cereus, Candida
      albicans and Microsporum audouinii.

PMID- 22863714
TI  - The asymmetric syntheses of methyl D-digitoxoside, L-oleandrose and L-cymarose
      from methyl sorbate, an achiral precursor.
AB  - The addition of 4 eq of chloral to osmundalactone (4S,5R)-4 gave quantitative
      formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane
      sulfonic acid to afford the intramolecular Micheal addition product (+)
      (3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-delta-lactone in 78% overall yield
      from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to
      methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D
      digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl
      osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic
      catalyst gave 3,4-trans-delta-lactone (-)-(3S,4R,5S)-20 in 28% yield and 3,4-cis
      delta-lactone (-)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (-)-(3S,4R,5S)
      20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall
      yield, while Dibal-H reduction of (-)-(3R,4R,5S)-21 followed by catalytic
      hydrogenation provided L-cymarose (7) in 85% overall yield.

PMID- 22863715
TI  - Three new resin glycosides and a new tetrahydropyran derivative from the seeds of
      Quamoclit pennata.
AB  - Three new resin glycosides, quamoclins V (1), VI (2), and VII (3) and a new
      tetrahydropyran derivative, quamopyran (4), were isolated from the seeds of
      Quamoclit pennata BOJER (Convolvulaceae). The chemical structures of these
      compounds were determined primarily on the basis of spectroscopic data. The
      carboxyl group of the aglycone, 11S-convolvulinolic acid, of 1 and 2 was linked
      intermoleculary with a hydroxy group of the sugar moiety to form a macrocyclic
      ester structure, as in already known jalapins, and 3 was an acylated glycosidic
      acid methyl ester. All of the sugar moieties of 1-3 were acylated by one 2S
      methylbutyric acid. Compound 4 was a diketone having a tetrahydropyran ring.

PMID- 22863716
TI  - Total synthesis of hydroxy-alpha- and hydroxy-beta-sanshool using Suzuki-Miyaura
      coupling.
AB  - Here, we describe the first total synthesis of hydroxyl-alpha- and hydroxyl-beta
      sanshool, which involves Suzuki-Miyaura coupling (SMC). Hydroxy-alpha-sanshool
      (1) was synthesized by SMC of bromoalkyne 4 with boronate 3 followed by (Z)
      selective reduction of the triple bond in the coupling product. Hydroxy-beta
      sanshool (2) was synthesized by regio- and (E)-selective conversion of 4 to
      iodoalkene 11 followed by SMC with 3.

PMID- 22863717
TI  - Mice overexpression of human augmenter of liver regeneration (hALR) in male germ
      cells shows abnormal spermatogenesis and reduced fertility.
AB  - Human augmenter of liver regeneration (hALR) is a sulfhydryl oxidase that is
      highly expressed in spermatogonia and early spermatocytes.  To investigate the
      physiological effects of hALR in spermatogenesis, we generated a hALR transgenic
      mouse model driven by the human TSPY (testis-specific protein, Y-encoded)
      promoter that allows the transgene to be specifically activated in the testes. 
      hALR content was found to be increased in both germ cells.  The histological and
      TUNEL analysis of transgenic testes revealed a number of spermatogenetic defects
      including primary spermatocyte overpopulation followed by depletion through
      apoptosis, degenerating and detached nucleated germ cells, haploid cell loss and
      intraepithelial vacuoles of varying sizes.  In line with these features, adult
      transgenic male mice also displayed a reduction in fertility.  Our data suggest
      that regulated spatial and temporal expression of hALR is required for normal
      testicular development and spermatogenesis, and overexpression of hALR results in
      influencing the sperm morphology and quantity and the eventual reduction in male
      fertility.  Present findings in the mouse may be of interest to human male
      fertility.

PMID- 22863718
TI  - CD40 C/T-1 polymorphism plays different roles in Graves' disease and Hashimoto's
      thyroiditis: a meta-analysis.
AB  - CD40 plays a pathogenic role in various autoimmune diseases.  However, studies
      investigating the association between CD40 C/T-1 polymorphism and autoimmune
      thyroid diseases risk have reported conflicting results and their relative
      population effect remains unclear; therefore, a meta-analysis was conducted.  
      The data for this meta-analysis included 14 (4214 cases and 3851 controls) and 4
      studies (623 cases and 774 controls) for the association of the CD40 C/T-1
      polymorphism with Graves' disease (GD) and Hashimoto's thyroiditis (HT),
      respectively. Results suggested significant association for CD40 C/T-1
      polymorphism (odds ratio 1.267 per C allele, p = 0.000) with GD but without HT.  
      The individuals who carried the C/C or C/T genotype have significantly increased
      GD risk compared with those who carried T/T genotype (C/C vs. T/T: OR = 1.596,
      95% CI, 1.256~2.028; C/T vs. T/T: OR = 1.210, 95% CI, 1.032~1.419; dominant
      model: OR = 1.366, 95% CI, 1.175~1.587; recessive model: OR = 1.322, 95% CI,
      1.147~1.523), while no association was observed in HT.   When stratified by
      ethnicity, the significant association between polymorphism and GD risk of
      Caucasians was found only in recessive models; but that of Asians was found in
      all models.   In the subgroup analysis of study design, we found thyroid antibody
      status should be ascertained in controls and euthyroidism subjects with higher
      levels of thyroid antibody should be excluded from control and included into HT
      to avoid bias.   Our meta-analysis showed that CD40 C/T-1 polymorphism plays
      different roles in GD and HT.   Further studies will be needed to confirm our
      findings.

PMID- 22863719
TI  - Pilot study of interleukin-27 in pathogenesis of dermatomyositis and
      polymyositis: associated with interstitial lung diseases.
AB  - OBJECTIVE: To determine whether interleukin (IL)-27 is involved in
      dermatomyositis (DM) and polymyositis (PM). METHODS: Serum IL-27, IL-18 and
      interferon-gamma (IFN-gamma) levels in 37 DM and 15 PM were detected by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Serum IL-27, IL-18 and IFN-gamma
      levels were significantly higher in DM and PM patients than in healthy controls.
      Significant higher levels of IL-27 were found in high creatine kinase (CK) level
      group and in patients with interstitial lung disease (ILD). Level of IL-27 was
      correlated with global 100-mm visual analog scales (VASs) score in patients with
      PM. CONCLUSION: These data supports the hypothesis that IL-27 maybe involved in
      DM and PM pathogenesis.

PMID- 22863720
TI  - Elevated circulating osteoprotegerin and reduced matrix-metalloprotease-9 in post
      menopausal women with chronic Hepatitis C virus infection.
AB  - The failure of the immune response to clear the Hepatitis C virus (HCV) results
      in chronic inflammation that leads to liver cirrhosis. In general, women have a
      better prognosis than men and this may be associated with increased levels of
      anti-inflammatory mediators that are positively regulated by female sex hormones.
      Our aim was to determine if a cohort of Irish women who acquired infection
      through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from
      a single source, had altered levels of circulating cytokine levels compared to
      women who spontaneously resolved infection, men with HCV infection or age-matched
      healthy controls. Twenty post-menopausal women and 20 men with chronic HCV
      infection (genotype 1), 20 post-menopausal women who resolved infection and age
      and sex-matched controls were recruited for the study. Levels of circulating
      cytokines were assessed by ELISA. Circulating IL-6, Oncostatin-M, TNF-alpha,
      CXCL10, CCL18, VEGF and GM-CSF did not differ between groups. Both men and women
      with HCV had significantly elevated levels of circulating Osteoprotegerin (OPG).
      However, male but not female HCV patients had elevated levels of circulating
      Matrix Metalloprotease-9 (MMP-9). An increased OPG: MMP-9 ratio in the
      circulation of females compared to males with chronic HCV may help protect
      against HCV-associated liver disease and explain the slow progress of liver
      disease in this cohort.

PMID- 22863721
TI  - Ameliorative effect of grape seed proanthocyanidin extract on thioacetamide
      induced mouse hepatic fibrosis.
AB  - The present study was designed to examine the effect of the grape seed
      proanthocyanidin extract (GSPE) on developing hepatic fibrosis that was induced
      by thioacetamide (TAA) in mice. Administration of TAA for 9 weeks led to a
      serious necrosis and apoptosis of the parenchymal cells, which resulted in an
      accumulation of excessive collagen in the liver and an increase of transformed
      hepatic stellate cells (HSCs). In addition, the mRNA expression of transforming
      growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), as the
      marker of the activated HSCs, and alpha1-(I)-collagen were all up-regulated
      significantly when compared with the control. However, combined oral
      administration of GSPE at 100 mg/kg suppressed the mRNA expression of TGF-beta1
      and alpha-SMA, with decreased collagen accumulation as demonstrated by
      histomorphological evaluation and quantitative RT-PCR. The mRNA expression of the
      pro-inflammatory factors, including inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2), was remarkably enhanced by TAA treatment. However,
      their levels displayed a down-regulated trend beyond simultaneous GSPE treatment.
      Moreover, GSPE administration markedly suppressed lipid peroxidation. In
      conclusion, as a plant antioxidant, GSPE manifested effective hepatocellular
      protective action to ameliorate the developing liver fibrosis induced by chronic
      TAA administration in mice.

PMID- 22863722
TI  - Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as
      salvage therapy for refractory/relapsed myeloma patients.
AB  - Relapse after dose-reduced allograft in advanced myeloma patients remains high.
      To reduce the risk of relapse, we investigated a myeloablative toxicity-reduced
      allograft (aSCT) consisting of i.v. BU and CY followed by lenalidomide
      maintenance therapy in 33 patients with multiple myeloma (MM) who relapsed
      following an autograft after a median of 12 months. The cumulative incidence of
      non-relapse mortality at 1 year was 6% (95% confidence interval (CI): 0-14).
      After a median interval of 168 days following aSCT, 24 patients started with a
      median dose of 5 mg (r, 5-15) lenalidomide without dexamethasone. During follow
      up, 13 patients discontinued lenalidomide owing to progressive disease (n=6),
      GvHD (n=3), thrombocytopenia (n=2), or fatigue (n=2). Major toxicities of
      lenalidomide were GvHD II-III (28%), viral reactivation (16%), thrombocytopenia
      (III-IV degrees ,16%), neutropenia (III/IV degrees , 8%), peripheral neuropathy
      (I/II degrees , 16%), or other infectious complication (8%). Cumulative incidence
      of relapse at 3 years was 42% (95% CI: 18-66). The 3-year estimated probability
      of PFS and OS was 52% (95% CI: 28-76) and 79% (95% CI: 63-95), respectively.
      Toxicity-reduced myeloablative allograft followed by lenalidomide maintenance is
      feasible and effective in relapsed patients with MM, but the induction of GvHD
      should be considered.

PMID- 22863723
TI  - Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1
      allele-matched unrelated donor and likelihood of subsequent transplant
      utilization.
AB  - Factors relevant to finding a suitable unrelated donor and barriers to effective
      transplant utilization are incompletely understood. Among a consecutive series of
      unrelated searches (n=531), an 8/8 HLA-A, -B, -C and -DRB1-matched unrelated
      donor was available for 289 (54%) patients, 7/8 for 159 (30%) and no donor for 83
      (16%). Patients of Caucasian race (P<0.0001) were more likely to find a donor.
      Younger age (P=0.01), Caucasian race (P=0.03), lower CIBMTR (Center for
      International Blood and Marrow Transplantation Research) risk (P=0.005), and 8/8
      HLA matching (P=0.005) were associated with higher odds of reaching hematopoietic
      cell transplantation (HCT). In a univariate analysis of OS, finding a donor was
      associated with hazard ratio (HR) of 0.85 (95% CI 0.63-1.2), P=0.31. Karnofsky
      performance status (KPS) accounted for interaction between having a donor and
      survival. Patients with KPS 90-100 and a donor had significantly reduced hazard
      for death (HR 0.59, 95% CI 0.38-0.90, P=0.02). These data provide estimates of
      the probability to find an unrelated donor in the era of high-resolution HLA
      typing, and identify potentially modifiable barriers to reaching HCT. Further
      efforts are needed to enhance effective donor identification and transplant
      utilization, particularly in non-Caucasian ethnic groups.

PMID- 22863724
TI  - Long-term survival in patients with metastatic breast cancer receiving
      intensified chemotherapy and stem cell rescue: data from the Italian registry.
AB  - The median survival of women with metastatic breast cancer (MBC) is 18-24 months,
      and fewer than 5% are alive and disease free at 5 years. We report toxicity and
      survival in a cohort of MBC patients receiving high-dose chemotherapy (HDC) with
      autologous hematopoietic SCT (AHSCT) in Italy between 1990 and 2005. Data set for
      survival analysis has been obtained for 415 patients. Clinical parameters
      including probability of transplant-related mortality (TRM), PFS and OS. With a
      median follow-up of 27 months (range 0-172), OS and PFS at 5 and 10 years in the
      whole population were 47/23 and 32/14%, respectively. A total 239 patients are
      alive with a median follow-up of 33 months (range 2-174). Survival was
      significantly more pronounced in patients harboring hormone receptor positive
      tumors (P=0.028), without visceral metastases (P=0.009) and in women with
      chemosensitive disease (P<0.0001). Sixty eight patients (20.4%) who received HDC
      in partial response, stable or progressive disease underwent conversion to CR.
      TRM was 2.5% overall and 1.3% since 2000. Our findings suggest that could be a
      role for HDC and AHSCT in delaying disease progression and possibly cure a subset
      of MBC patient harboring chemosensitive tumors.

PMID- 22863725
TI  - More than skin deep? Emerging therapies for chronic cutaneous GVHD.
AB  - The options for treating skin disease after haemopoietic progenitor cell
      transplant (HPCT) have broadened considerably over the last decade to include
      much more than topical steroids and emollients. This article reviews current and
      emerging therapies for chronic cutaneous GVHD, a well-recognised complication of
      HPCT. Alongside skin-directed therapies, there is now a wide range of systemic
      agents with differing targets for which an evidence base is emerging. Of
      particular interest, we summarise the role of electrocorporeal photopheresis, a
      therapy increasingly used in the United Kingdom to treat severe sclerodermoid
      manifestations of GVHD. We include a discussion of the expanding knowledge of the
      pathogenesis of cutaneous GVHD, which is informing our understanding and
      development of second line therapies (for example, the role of B cells and the
      utility of rituximab). Additionally, we draw attention to challenges encountered
      in the evaluation of chronic GVHD treatments and highlight recommendations for
      further research that may enable haematologists and dermatologists to provide
      better care for these patients. Finally, we present a clinical algorithm to aid
      the approach to treating limited and extensive disease and steroid refractory or
      persistent disease where steroid sparing may be necessary.

PMID- 22863726
TI  - G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or
      incomplete engraftment after allogeneic hematopoietic transplantation.
AB  - There is little data comparing the activity and toxicity of donor lymphocyte
      therapy with granulocyte (G)-CSF-mobilized cells (G-donor lymphocyte infusion
      (DLI)) with the conventionally collected DLI (C-DLI) after allogeneic blood or
      marrow transplantation. We retrospectively evaluated 67 patients to compare the
      efficacy and toxicity of GCSF-mobilized DLI with C-DLI in the treatment of
      relapse of malignant disease or poor donor engraftment post transplant. We
      assessed clinical outcomes that may represent the immunological outcome of DLI.
      The median OS was 210 days (range 3-2436 days), 291 days (range 17-1491 days) in
      the G-DLI group (15 patients) and 207.5 days (range 3-2436 days) in the C-DLI
      group (52 patients). The median PFS time was 72 days (range 8-1491 days) in the G
      DLI group vs 82 days (range 1-2436 days) in the C-DLI group. Rates of post DLI
      GVHD and improvement in donor engraftment were similar in the G-DLI and C-DLI
      groups. We conclude that G-DLI appears to have similar therapeutic activity to
      that seen with C-DLI, and where such cells are available they may be substituted
      for conventional donor lymphocytes.

PMID- 22863727
TI  - Improved outcomes with novel agents and auto-SCT for multiple myeloma in African
      American patients.

PMID- 22863728
TI  - Biomarkers for acute GVHD: can we predict the unpredictable?
AB  - Acute GVHD remains an important complication after allogeneic hematopoietic cell
      transplantation (HCT). Many efforts have been devoted to identifying potential
      noninvasive peripheral blood biomarkers to help improve the diagnosis or
      management of acute GVHD while avoiding invasive tissue biopsies. Early attempts
      to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF
      alpha, however, both of these and others were not specific for GVHD, often being
      elevated in the setting of generalized inflammation, accompanying other major
      complications of HCT as well. More recent efforts have focused on additional
      cytokines and other cell-surface molecules, which function in leukocyte
      trafficking and activation with the hope that these can also serve as targets for
      novel therapeutic approaches. Modern proteomic methods have allowed the screening
      of large numbers of patient samples and yielded several novel candidate
      biomarkers, including elafin and reg3alpha, which may not be directly involved in
      the immunological pathogenesis of GVHD, but may be unique biomarkers for end
      organ injury. Combining these new molecules with traditionally identified
      cytokines to form an acute GVHD biomarker panel has recently shown the ability to
      predict outcomes in patients who develop acute GVHD. The ultimate goals of
      identifying a specific biomarker are to refine diagnosis, guide therapy and
      develop risk-adapted approaches in order to better treat patients and improve
      outcomes after allogeneic HCT. These approaches include differential treatment
      for patients who develop acute GVHD with a high-risk biomarker profile as well as
      pre-emptive therapy in patients after HCT prior to the development of symptoms.
      With the recent progress summarized below, these goals may soon be realized.

PMID- 22863729
TI  - Pulsed electric field assisted assembly of polyaniline.
AB  - Assembling conducting polyaniline (PANi) on pre-patterned nano-structures by a
      high rate, commercially viable route offers an opportunity for manufacturing
      devices with nanoscale features. In this work we report for the first time the
      use of pulsed electric field to assist electrophoresis for the assembly of
      conducting polyaniline on gold nanowire interdigitated templates. This technique
      offers dynamic control over heat build-up, which has been a main drawback in the
      DC electrophoresis and AC dielectrophoresis as well as the main cause of nanowire
      template damage. The use of this technique allowed higher voltages to be applied,
      resulting in shorter assembly times (e.g., 17.4 s, assembly resolution of 100
      nm). Moreover, the area coverage increases with the increase in number of pulses.
      A similar trend was observed with the deposition height and the increase in
      deposition height followed a linear trend with a correlation coefficient of 0.95.
      When the experimental mass deposited was compared with Hamaker's theoretical
      model, the two were found to be very close. The pre-patterned templates with PANi
      deposition were subsequently used to transfer the nanoscale assembled PANi from
      the rigid templates to thermoplastic polyurethane using the thermoforming
      process.

PMID- 22863730
TI  - The actin cytoskeleton participates in the early events of autophagosome
      formation upon starvation induced autophagy.
AB  - Autophagy is a process by which cytoplasmic material is sequestered in a double
      membrane vesicle destined for degradation. Nutrient deprivation stimulates the
      pathway and the number of autophagosomes in the cell increases in response to
      such stimulus. In the current report we have demonstrated that actin is necessary
      for starvation-mediated autophagy. When the actin cytoskeleton is depolymerized,
      the increase in autophagic vacuoles in response to the starvation stimulus was
      abolished without affecting maturation of remaining autophagosomes. In addition,
      actin filaments colocalized with ATG14, BECN1/Beclin1 and PtdIns3P-rich
      structures, and some of them have a typical omegasome shape stained with the
      double FYVE domain or ZFYVE1/DFCP1. In contrast, no major colocalization between
      actin and ULK1, ULK2, ATG5 or MAP1LC3/LC3 was observed. Taken together, our data
      indicate that actin has a role at very early stages of autophagosome formation
      linked to the PtdIns3P generation step. In addition, we have found that two
      members of the Rho family of proteins, RHOA and RAC1 have a regulatory function
      on starvation-mediated autophagy, but with opposite roles. Indeed, RHOA has an
      activatory role whereas Rac has an inhibitory one. We have also found that
      inhibition of the RHOA effector ROCK impaired the starvation-mediated autophagic
      response. We propose that actin participates in the initial membrane remodeling
      stage when cells require an enhanced rate of autophagosome formation, and this
      actin function would be tightly regulated by different members of the Rho family.

PMID- 22863731
TI  - Genome-wide association study identifies a susceptibility locus for thyrotoxic
      periodic paralysis at 17q24.3.
AB  - Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening
      complication of thyrotoxicosis. We conducted a genome-wide association study
      (GWAS) and a replication study with a total of 123 southern Chinese with TPP
      (cases) and 1,170 healthy controls and identified a susceptibility locus on
      chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis)
      = 1.8 * 10(-14)). All subjects with TPP also had Graves' disease, and subsequent
      TPP versus Graves' disease comparison confirmed that the association at 17q24.3
      was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk
      prediction of TPP in subjects with Graves' disease was 0.73. Expression
      quantitative trait locus (eQTL) analysis identified SNPs in the region flanking
      rs312691 (+/-10 kb) that could potentially affect KCNJ2 expression (P = 0.0001).
      Our study has identified a susceptibility locus associated with TPP and provides
      insight into the causes of TPP.

PMID- 22863732
TI  - Shigella sonnei genome sequencing and phylogenetic analysis indicate recent
      global dissemination from Europe.
AB  - Shigella are human-adapted Escherichia coli that have gained the ability to
      invade the human gut mucosa and cause dysentery(1,2), spreading efficiently via
      low-dose fecal-oral transmission(3,4). Historically, S. sonnei has been
      predominantly responsible for dysentery in developed countries but is now
      emerging as a problem in the developing world, seeming to replace the more
      diverse Shigella flexneri in areas undergoing economic development and
      improvements in water quality(4-6). Classical approaches have shown that S.
      sonnei is genetically conserved and clonal(7). We report here whole-genome
      sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows
      that the current S. sonnei population descends from a common ancestor that
      existed less than 500 years ago and that diversified into several distinct
      lineages with unique characteristics. Our analysis suggests that the majority of
      this diversification occurred in Europe and was followed by more recent
      establishment of local pathogen populations on other continents, predominantly
      due to the pandemic spread of a single, rapidly evolving, multidrug-resistant
      lineage.

PMID- 22863733
TI  - The malaria parasite Plasmodium vivax exhibits greater genetic diversity than
      Plasmodium falciparum.
AB  - We sequenced and annotated the genomes of four P. vivax strains collected from
      disparate geographic locations, tripling the number of genome sequences available
      for this understudied parasite and providing the first genome-wide perspective of
      global variability in this species. We observe approximately twice as much SNP
      diversity among these isolates as we do among a comparable collection of isolates
      of P. falciparum, a malaria-causing parasite that results in higher mortality.
      This indicates a distinct history of global colonization and/or a more stable
      demographic history for P. vivax relative to P. falciparum, which is thought to
      have undergone a recent population bottleneck. The SNP diversity, as well as
      additional microsatellite and gene family variability, suggests a capacity for
      greater functional variation in the global population of P. vivax. These findings
      warrant a deeper survey of variation in P. vivax to equip disease interventions
      targeting the distinctive biology of this neglected but major pathogen.

PMID- 22863734
TI  - Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate
      identify six new risk loci.
AB  - We have conducted the first meta-analyses for nonsyndromic cleft lip with or
      without cleft palate (NSCL/P) using data from the two largest genome-wide
      association studies published to date. We confirmed associations with all
      previously identified loci and identified six additional susceptibility regions
      (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic
      variability identified the first specific genetic risk factor for NSCLP
      (nonsyndromic cleft lip plus palate) (rs8001641; P(NSCLP) = 6.51 * 10(-11);
      homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16).

PMID- 22863736
TI  - Transgenerational maintenance of transgene body CG but not CHG and CHH
      methylation.
AB  - In plants, RNA-directed DNA methylation (RdDM) can target both transgene
      promoters and coding regions/gene bodies. RdDM leads to methylation of cytosines
      in all sequence contexts: CG, CHG and CHH. Upon segregation of the RdDM trigger,
      at least CG methylation can be maintained at promoter regions in the progeny. So
      far, it is not clear whether coding region methylation can be also maintained. We
      showed that the body of Potato spindle tuber viroid (PSTVd) transgene constructs
      became densely de novo methylated at CG, CHG and CHH sites upon PSTVd infection.
      In this study, we demonstrate that in viroid-free progeny plants, asymmetric CHH
      and CHG methylation was completely lost. However, symmetric CG methylation was
      stably maintained for at least two generations. Importantly, the presence of
      transgene body methylation did not lead to an increase of dimethylation of
      histone H3 lysine 9 or a decrease of acetylation of H3. Our data supports the
      view that CG methylation can be maintained not only in promoters but also in the
      body of transgenes. They further suggest that maintenance of methylation may
      occur independently of tested chromatin modifications.

PMID- 22863737
TI  - Spatial-temporal reorganization of activated integrins.
AB  - Integrin receptors play important roles in cell adhesion and tumor metastasis.
      The coupling of mechanical sensing and biochemical ligation is known to
      collectively regulate the activation of integrin receptors. Recently,
      oligomerization of activated integrins has been considered as the primordial
      signature of cytoskeletal remodeling and the initiation of various downstream
      signals, such as focal and fibrillar adhesions. However, spatio-temporal
      reorganization of activated integrins and associated proteins remains poorly
      understood. Here, we summarized the recent discovery of sequential biophysical
      events of integrin activation during early adhesion formation. Using the cyclic
      Arg-Gly-Asp (RGD) peptide as a mobile ligand on supported lipid membranes, a
      series of previously unreported events were observed following integrin
      alphavbeta3 clustering and cell spreading, including a long-range lateral
      translocation of the integrin clusters. With initial clustering, localized actin
      polymerization occurred in a Src family kinase dependent manner. Clustering of
      liganded integrins recruits various adaptor proteins and serves as a reaction
      core for mechanobiological activities. In addition, there are future
      possibilities to investigate the role of other synergetic interactions with the
      activated integrin receptors.

PMID- 22863738
TI  - Tumor microenvironment indoctrination: an emerging hallmark of cancer.
AB  - Nastiness of cancer does not only reside in the corruption of cancer cells by
      genetic aberrations that drive their sustained proliferative power--the roots of
      malignancy--but also in its aptitude to reciprocally sculpt its surrounding
      environment and cellular stromal ecosystem, in such a way that the corrupted
      tumor microenvironment becomes a full pro-tumorigenic entity. Such a contribution
      had been appreciated three decades ago already, with the discovery of tumor
      angiogenesis and extracellular matrix remodeling. Nevertheless, the recent
      emergence of the tumor microenvironment as the critical determinant in cancer
      biology is paralleled by the promising therapeutic potential it carries, opening
      alternate routes to fight cancer. The study of the tumor microenvironment
      recruited numerous lead-scientists over the years, with distinct perspectives,
      and some of them have kindly accepted to contribute to the elaboration of this
      special issue entitled Tumor microenvironment indoctrination: An emerging
      hallmark of cancer.

PMID- 22863735
TI  - Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and
      the monkey malaria clade.
AB  - P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the
      sister taxon of P. vivax, the most prevalent malaria-causing species in humans
      outside of Africa. Because P. cynomolgi shares many phenotypic, biological and
      genetic characteristics with P. vivax, we generated draft genome sequences for
      three P. cynomolgi strains and performed genomic analysis comparing them with the
      P. vivax genome, as well as with the genome of a third previously sequenced
      simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey
      malaria clade can be characterized by copy-number variants (CNVs) in multigene
      families involved in evasion of the human immune system and invasion of host
      erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P.
      cynomolgi genome, providing a map of genetic variation that can be used to map
      parasite traits and study parasite populations. The sequencing of the P.
      cynomolgi genome is a critical step in developing a model system for P. vivax
      research and in counteracting the neglect of P. vivax.

PMID- 22863739
TI  - Mesenchymal stem cells in tumor development: emerging roles and concepts.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitor cells that participate
      in the structural and functional maintenance of connective tissues under normal
      homeostasis. They also act as trophic mediators during tissue repair, generating
      bioactive molecules that help in tissue regeneration following injury. MSCs serve
      comparable roles in cases of malignancy and are becoming increasingly appreciated
      as critical components of the tumor microenvironment. MSCs home to developing
      tumors with great affinity, where they exacerbate cancer cell proliferation,
      motility, invasion and metastasis, foster angiogenesis, promote tumor desmoplasia
      and suppress anti-tumor immune responses. These multifaceted roles emerge as a
      product of reciprocal interactions occurring between MSCs and cancer cells and
      serve to alter the tumor milieu, setting into motion a dynamic co-evolution of
      both tumor and stromal tissues that favors tumor progression. Here, we summarize
      our current knowledge about the involvement of MSCs in cancer pathogenesis and
      review accumulating evidence that have placed them at the center of the pro
      malignant tumor stroma.

PMID- 22863740
TI  - Controlling matrix stiffness and topography for the study of tumor cell
      migration.
AB  - Cellular studies have long been performed on the bench top, within Petri dishes
      and flasks that expose cells to surroundings that differ greatly from their
      native environment. The complexity of a human tissue is such that to truly
      replicate a cell's physiologic microenvironment in vitro is currently impossible.
      It is nevertheless important to determine how various factors of the
      microenvironment interact to drive cell behavior, particularly with regard to
      disease states, such as cancer. Here we focus on two key elements of the cellular
      microenvironment, matrix stiffness and architecture, in the context of tumor cell
      behavior. We discuss recent work focusing on the effects of these individual
      properties on cancer cell migration and describe one technique developed by our
      lab that could be applied to dissect the effects of specific structural and
      mechanical cues, and which may lead to useful insights into the potentially
      synergistic effects of these properties on tumor cell behavior.

PMID- 22863742
TI  - A facile one-step approach to obtaining uniform matchstick-like Ag2S-CdS
      nanoheterostructures.
AB  - A simple and facile method for synthesizing Ag(2)S-CdS nanoheterostructures has
      been introduced. With a one-step hydrothermal reaction, Ag(2)S-CdS
      nanoheterostructures with high uniformity in morphology and structure can be
      obtained. The Ag(2)S-CdS nanoheterostructures exhibit matchstick-like morphology,
      composed of spherical Ag(2)S heads and CdS rods. The influences of the reaction
      temperature, reaction time and molar ratio between Ag and Cd sources were
      explored, the results suggesting that the growth can be ascribed to the in situ
      phase transfer of Ag and Cd sources from the aqueous phase to the organic phase
      and the subsequent catalyst-assisted growth.

PMID- 22863741
TI  - An "elite hacker": breast tumors exploit the normal microenvironment program to
      instruct their progression and biological diversity.
AB  - The year 2011 marked the 40 year anniversary of Richard Nixon signing the
      National Cancer Act, thus declaring the beginning of the "War on Cancer" in the
      United States. Whereas we have made tremendous progress toward understanding the
      genetics of tumors in the past four decades, and in developing enabling
      technology to dissect the molecular underpinnings of cancer at unprecedented
      resolution, it is only recently that the important role of the stromal
      microenvironment has been studied in detail. Cancer is a tissue-specific disease,
      and it is becoming clear that much of what we know about breast cancer
      progression parallels the biology of the normal breast differentiation, of which
      there is still much to learn. In particular, the normal breast and breast tumors
      share molecular, cellular, systemic and microenvironmental influences necessary
      for their progression. It is therefore enticing to consider a tumor to be a
      "rogue hacker"--one who exploits the weaknesses of a normal program for personal
      benefit. Understanding normal mammary gland biology and its "security
      vulnerabilities" may thus leave us better equipped to target breast cancer. In
      this review, we will provide a brief overview of the heterotypic cellular and
      molecular interactions within the microenvironment of the developing mammary
      gland that are necessary for functional differentiation, provide evidence
      suggesting that similar biology--albeit imbalanced and exaggerated--is observed
      in breast cancer progression particularly during the transition from carcinoma in
      situ to invasive disease. Lastly we will present evidence suggesting that the
      multigene signatures currently used to model cancer heterogeneity and clinical
      outcome largely reflect signaling from a heterogeneous microenvironment-a
      recurring theme that could potentially be exploited therapeutically.

PMID- 22863743
TI  - AGO4 regulates entry into meiosis and influences silencing of sex chromosomes in
      the male mouse germline.
AB  - The four mammalian Argonaute family members are thought to share redundant
      functions in the microRNA pathway, yet only AGO2 possesses the catalytic "slicer"
      function required for RNAi. Whether AGO1, AGO3, or AGO4 possesses specialized
      functions remains unclear. Here we show that AGO4 localizes to spermatocyte
      nuclei during meiotic prophase I, specifically at sites of asynapsis and the
      transcriptionally silenced XY subdomain, the sex body. We generated Ago4 knockout
      mice and show that Ago4(-/-) spermatogonia initiate meiosis early, resulting from
      premature induction of retinoic acid-response genes. During prophase I, the sex
      body assembles incorrectly in Ago4(-/-) mice, leading to disrupted meiotic sex
      chromosome inactivation (MSCI). This is associated with a dramatic loss of
      microRNAs, >20% of which arises from the X chromosome. Thus, AGO4 regulates
      meiotic entry and MSCI in mammalian germ cells, implicating small RNA pathways in
      these processes.

PMID- 22863745
TI  - Doxorubicin-loaded Zein in situ gel for interstitial chemotherapy.
AB  - A novel drug delivery system of doxorubicin (DOX)-loaded Zein in situ gel for
      interstitial chemotherapy was investigated in this study. The possible mechanisms
      of drug release were described according to morphological analysis by optical
      microscopy and scanning electronic microscope (SEM). In vitro and in vivo anti
      tumor activity studies showed that DOX-loaded Zein in situ gel was superior to
      DOX solution. Local pharmacokinetics in tumor tissue was studied by quantitative
      analysis with confocal laser scanning microscopy (CLSM) combined with
      microdialysis technology. A pharmacokinetics mathematical model of DOX-loaded
      Zein in situ gel in tumors was then built.

PMID- 22863744
TI  - Sizzled-tolloid interactions maintain foregut progenitors by regulating
      fibronectin-dependent BMP signaling.
AB  - The liver, pancreas, and lungs are induced from endoderm progenitors by a series
      of dynamic growth factor signals from the mesoderm, but how the temporal-spatial
      activity of these signals is controlled is poorly understood. We have identified
      an extracellular regulatory loop required for robust bone morphogenetic protein
      (BMP) signaling in the Xenopus foregut. We show that BMP signaling is required to
      maintain foregut progenitors and induce expression of the secreted frizzled
      related protein Sizzled (Szl) and the extracellular metalloprotease Tolloid-like
      1 (Tll1). Szl negatively regulates Tll activity to control deposition of a
      fibronectin (FN) matrix between the mesoderm and endoderm, which is required to
      maintain BMP signaling. Foregut-specific Szl depletion results in a loss of the
      FN matrix and failure to maintain robust pSmad1 levels, causing a loss of foregut
      gene expression and organ agenesis. These results have implications for BMP
      signaling in diverse contexts and the differentiation of foregut tissue from stem
      cells.

PMID- 22863746
TI  - [Completeness and quality of multidisciplinary team meetings: the example of
      breast cancer in Tarn].
AB  - To facilitate multidisciplinary team meetings' (MTM) management, the cancer
      research networks developed a communicating file. The Midi-Pyrenees region
      includes the Oncomip network and a cancer registry in the department of Tarn.
      Their collaboration allows the assessment of the care given to patients. The
      objectives of this study were to measure the completeness of the presentation to
      MTM of patients and its determinants (age and prognostic factors), and to study
      the quality of MTM for breast cancer diagnosed in the Tarn in 2007. A track of
      presentation to MTM chronologically conform was found in 70.5%. The completeness
      of presentation seemed lower for the oldest women and the parameters conditioning
      the decision of a non-surgical treatment were associated with a more frequent
      presentation to MTM. The quorum was respected for 53.9% of cases presented before
      all treatment and for 71.3% of cases presented after surgery. The partnership,
      which exists between the Tarn cancer registry and the Oncomip network, makes the
      realization of similar studies in population with other type of cancer possible.

PMID- 22863747
TI  - Calorimetric measurement of water transport and intracellular ice formation
      during freezing in cell suspensions.
AB  - The current study presents a new and novel analysis of heat release signatures
      measured by a differential scanning calorimeter (DSC) associated with water
      transport (WT), intracellular ice formation (IIF) and extracellular ice formation
      (EIF). Correlative cryomicroscopy experiments were also performed to validate the
      DSC data. The DSC and cryomicroscopy experiments were performed on human dermal
      fibroblast cells (HDFs) at various cytocrit values (0-0.8) at various cooling
      rates (0.5-250  degrees C/min). A comparison of the cryomicroscopy experiments
      with the DSC analysis show reasonable agreement in the water transport (cellular
      dehydration) and IIF characteristics between both the techniques with the caveat
      that IIF measured by DSC lagged that measured by cryomicroscopy. This was
      ascribed to differences in the techniques (i.e. cell vs. bulk measurement) and
      the possibility that not all IIF is associated with visual darkening. High and
      low rates of 0.5  degrees C/min and 250  degrees C/min were chosen as HDFs did
      not exhibit significant IIF or WT at each of these extremes respectively.
      Analysis of post-thaw viability data suggested that 10  degrees C/min was the
      presumptive optimal cooling rate for HDFs and was independent of the cytocrit
      value. The ratio of measured heat values associated with IIF (q(IIF)) to the
      total heat released from both IIF and water transport or from the total cell
      water content in the sample (q(CW)) was also found to increase as the cooling
      rate was increased from 10 to 250  degrees C/min and was independent of the
      sample cytocrit value. Taken together, these observations suggest that the
      proposed analysis is capable of deconvolving water transport and IIF data from
      the measured DSC latent heat thermograms in cell suspensions during freezing.

PMID- 22863748
TI  - Prompt increases in retinol-binding protein 4 and endothelial progenitor cells
      during acute exercise load in diabetic subjects.
AB  - The present study was undertaken to determine whether acute exercise load alters
      serum retinol-binding protein 4 (RBP4) and numbers of endothelial progenitor
      cells (EPC) in diabetic subjects.  Sixty-two subjects with type 2 diabetes
      mellitus were enrolled in the present study.  They were 50 males and 12 females
      with the ages of 65.1+/-8.1 (mean +/- SD) years.  Cardio-pulmonary exercise
      stress test (CPX) was carried out, and the numbers of EPC and serum RBP4 levels
      before and after the CPX were measured.  RBP4 is a cytokine synthesized in
      hepatocytes, white adipose tissues and skeletal muscles, and serum RBP4 was
      determined by ELISA.  EPC was determined as CD34(+)/133(+) cells by FACS.  The
      subjects were subgrouped into two groups with or without nephropathy.  Serum RBP4
      levels promptly increased from 48.2+/-4.3 (mean+/-SEM) to 54.3+/-4.2 MUg/mL after
      the CPX (mean exercise time of 8 min) in the diabetic subjects without
      nephropathy (p=0.0006), but did not in those with nephropathy.  There was a
      positive correlation between changes in serum RBP4 during the exercise and
      estimated glomerular filtration rate (r=0.30, p=0.018).  Also, an acute exercise
      load promptly increased the number of EPCs in the diabetic subjects with and
      without nephropathy.  These findings suggest that a prompt increase in exercise
      induced RBP4 is retarded by progression of nephropathy, and that an exercise
      induced mobilization of EPCs could maintain endothelial cells in diabetic
      subjects.

PMID- 22863749
TI  - KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas.
AB  - Adrenal aldosterone-producing adenomas (APA) are rarely associated with the clear
      co-secretion of cortisol. Somatic mutations of the potassium channel KCNJ5 gene,
      with the hotspots G151R and L168R, have been recently identified in patients with
      APA. However, whether APAs that secrete cortisol have these mutations remains
      unclear. We examined three patients with APAs showing clear autonomous secretion
      of cortisol who possessed a 1 mg dexamethasone suppression test (DST) with a
      failure of the serum cortisol level to drop below 3.0 MUg/dL, a morning plasma
      ACTH level of less than 10 pg/mL, and suppressed accumulation in the intact
      adrenal on (131)I- adosterol scintigraphy, or postoperative adrenal
      insufficiency. Laparoscopic adrenectomy revealed all tumors to be golden yellow,
      and histological examination confirmed them to be adrenocortical adenomas. All
      these patients required replacement therapy with hydrocortisone after surgery.
      Sequencing demonstrated that 2 of three cases showed a mutation of the KCNJ5
      gene, one with c.451G>A, p.G151R and one with c.503T>G, p.L168R. Furthermore, the
      mRNA levels of steroidogenic enzymes including CYP11B1, CYP11B2, HSD3B2, CYP17A1,
      CYP11A1 and KCNJ5 in the 3 cases did not differ from those in 8 pure APAs not
      showing any of the above conditions for autonomous cortisol secretion. In
      addition, all 8 pure APAs harbored mutations of the KCNJ5 gene. These findings
      suggested that at least some aldosterone- and cortisol-co-secreting adrenal
      tumors have mutations of the KCNJ5 gene, suggesting the origin to be APA, and
      pure APAs may show a high incidence of KCNJ5 mutations.

PMID- 22863750
TI  - Implementation of atomically defined field ion microscopy tips in scanning probe
      microscopy.
AB  - The field ion microscope (FIM) can be used to characterize the atomic
      configuration of the apices of sharp tips. These tips are well suited for
      scanning probe microscope (SPM) use since they predetermine the SPM resolution
      and the electronic structure for spectroscopy. A protocol is proposed for
      preserving the atomic structure of the tip apex from etching due to gas
      impurities during the period of transfer from the FIM to the SPM, and estimations
      are made regarding the time limitations of such an experiment due to
      contamination with ultra-high vacuum rest gases. While avoiding any current
      setpoint overshoot to preserve the tip integrity, we present results from
      approaches of atomically defined tungsten tips to the tunneling regime with
      Au(111), HOPG (highly oriented  pyrolytic graphite) and Si(111) surfaces at room
      temperature. We conclude from these experiments that adatom mobility  and
      physisorbed gas on the sample surface limit the choice of surfaces for which the
      tip integrity is preserved in tunneling experiments at room temperature. The
      atomic structure of FIM tip apices is unchanged only after tunneling to the
      highly reactive Si(111) surface.

PMID- 22863751
TI  - PLA nanoparticles coated with a beta-cyclodextrin polymer shell: preparation,
      characterization and release kinetics of a hydrophobic compound.
AB  - The aim of this work was to incorporate a hydrophobic compound benzophenone (BP)
      into core-shell nanoparticles (NPs) and to study its release. The core of these
      NPs is based on polylactic acid (PLA) and serves as a nanocontainer to
      accommodate BP. The shell is constituted of a beta-cyclodextrin polymer (Poly
      beta-CD) which ensures the control of BP release through non-covalent host-guest
      interactions. Studies were focused on the preparation, physico-chemical analysis
      of the BP-loaded NPs and on the elucidation of the release mechanisms. The main
      features which are the slow kinetics, the dilution-induced release and the total
      release of encapsulated BP are in good agreement with a mechanism mainly
      controlled by diffusion of BP and by its binding with the beta-CDs cavities
      present at the surface of NPs.

PMID- 22863752
TI  - TGF-beta is responsible for NK cell immaturity during ontogeny and increased
      susceptibility to infection during mouse infancy.
AB  - A large gap in our understanding of infant immunity is why natural killer (NK)
      cell responses are deficient, which makes infants more prone to viral infection.
      Here we demonstrate that transforming growth factor-beta (TGF-beta) was
      responsible for NK cell immaturity during infancy. We found more fully mature NK
      cells in CD11c(dnR) mice, whose NK cells lack TGF-beta receptor (TGF-betaR)
      signaling. Ontogenic maturation of NK cells progressed faster in the absence of
      TGF-beta signaling, which results in the formation of a mature NK cell pool early
      in life. As a consequence, infant CD11c(dnR) mice efficiently controlled viral
      infections. These data thus demonstrate an unprecedented role for TGF-beta in
      ontogeny that can explain why NK cell responses are deficient early in life.

PMID- 22863754
TI  - Single-row versus double-row repair of the distal Achilles tendon: a
      biomechanical comparison.
AB  - Surgery for recalcitrant insertional Achilles tendinopathy often consists of
      partial or total release of the insertion site, debridement of the diseased
      portion of the tendon, calcaneal ostectomy, and reattachment of the Achilles to
      the calcaneus. Although single-row and double-row techniques exist for repair of
      the detached Achilles tendon, biomechanical data are lacking to support one
      technique over the other. Based on data extrapolated from the study of rotator
      cuff repairs, we hypothesized that a double-row construct would provide superior
      fixation strength over a single-row repair. Eighteen human cadaveric Achilles
      tendons (9 matched pairs) with attached calcanei were repaired with single-row or
      double-row techniques. Specimens were mounted in a servohydraulic materials
      testing machine, subjected to a preconditioning cycle, and loaded to failure.
      Failure was defined as suture breakage or pullout, midsubstance tendon rupture,
      or anchor pullout. Among the failures were 12 suture failures, 5 proximal-row
      anchor failures, and 1 distal-row anchor failure. No midsubstance tendon ruptures
      or testing apparatus failures were observed. There were no statistically
      significant differences in the peak load to failure between the single-row and
      double-row repairs (p = .46). Similarly, no significant differences were observed
      with regards to mean energy expenditure to failure (p = .069). The present study
      demonstrated no biomechanical advantages of the double-row repair over a single
      row repair. Despite the lack of a clear biomechanical advantage, there may exist
      clinical advantages of a double-row repair, such as reduction in knot prominence
      and restoration of the Achilles footprint.

PMID- 22863753
TI  - The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via
      modification of the signaling adaptor TRAF6 and transcription factor NF-kappaB.
AB  - Several members of the NLR family of sensors activate innate immunity. In
      contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent
      activation of the transcription factor NF-kappaB by interacting with the TLR
      signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6
      and activation of NF-kappaB. We used bioinformatics to predict interactions
      between NLR and TRAF proteins, including interactions of TRAF with NLRC3. In
      vivo, macrophage expression of Nlrc3 mRNA was diminished by the administration of
      lipopolysaccharide (LPS) but was restored when cellular activation subsided. To
      assess biologic relevance, we generated Nlrc3(-/-) mice. LPS-treated Nlrc3(-/-)
      macrophages had more K63-ubiquitinated TRAF6, nuclear NF-kappaB and
      proinflammatory cytokines. Finally, LPS-treated Nlrc3(-/-) mice had more signs of
      inflammation. Thus, signaling via NLRC3 and TLR constitutes a negative feedback
      loop. Furthermore, prevalent NLR-TRAF interactions suggest the formation of a
      'TRAFasome' complex.

PMID- 22863755
TI  - Cancer immunotherapy products: regulatory aspects in the European Union.
AB  - Active immunotherapy products (widely known as "cancer vaccines") are products
      intended to stimulate an immune response to mediate tumor destruction or reduce
      the progression of disease in patients where cancer has been diagnosed. Some
      quality attributes of these products are very difficult to characterize or
      present a high variability (especially if they are for autologous use), further
      complicating the interpretation of some of the clinical data. Furthermore,
      questions arise in the evaluation of efficacy and safety data in comparison with
      current chemical or biological treatments for the same indications. Some of these
      aspects are discussed in this paper in relationship with the regulatory
      requirements in the European Union and as applied to two recently assessed
      medicinal products, Oncophage and Provenge, both considered therapeutic "cancer
      vaccines" for renal cell carcinoma and prostate cancer, respectively.

PMID- 22863757
TI  - Extrapulmonary lymphangioleiomyomatosis: a wolf in sheep's clothing.
AB  - We present a case of a 32-year-old woman who was diagnosed with
      lymphangioleiomyomatosis (LAM) after detecting a mass in the upper anterior
      mediastinum. Two years after presentation another metastatic localisation of LAM
      occurred in the cervical region. With this article we would like to highlight the
      fact that there are still a lot of unanswered questions, especially regarding the
      best management of extrapulmonary LAM.

PMID- 22863756
TI  - The detailed analysis of the changes of murine dendritic cells (DCs) induced by
      thymic peptide: pidotimod(PTD).
AB  - The aim of present research is to analyze the detailed changes of dendritic cells
      (DCs) induced by pidotimod(PTD). These impacts on DCs of both bone marrow derived
      DCs and established DC2.4 cell line were assessed with use of conventional
      scanning electron microscopy (SEM), flow cytometry (FCM), transmission electron
      microscopy (TEM), cytochemistry assay FITC-dextran, bio-assay and enzyme linked
      immunosorbent assay (ELISA). We demonstrated the ability of PTD to induce DC
      phynotypic and functional maturation as evidenced by higher expression of key
      surface molecules such as MHC II, CD80 and CD86. The functional tests proved the
      downregulation of ACP inside the DCs, occurred when phagocytosis of DCs
      decreased, with simultaneously antigen presentation increased toward maturation.
      Finally, PTD also stimulated production of more cytokine IL-12 and less TNF
      alpha. Therefore it is concluded that PTD can markedly exert positive induction
      to murine DCs.

PMID- 22863758
TI  - Changes in prevalence and load of airway bacteria using quantitative PCR in
      stable and exacerbated COPD.
AB  - BACKGROUND: Prevalence and load of airway bacteria in stable and exacerbated
      chronic obstructive pulmonary disease (COPD) has been previously studied using
      microbiological culture. Molecular techniques, such as quantitative PCR (qPCR),
      may be more informative. METHODS: In this study, 373 sputum samples from 134 COPD
      outpatients were assessed for prevalence and load of typical airway bacteria
      (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis) by
      multiplex qPCR, with 176 samples analysed for atypical bacteria. Paired stable
      and exacerbation typical bacteria data were compared in 52 patients. We compared
      routine culture with qPCR in 177/373 samples. RESULTS: Typical bacteria were more
      prevalent in exacerbation than stable-state paired samples: 30/52 (57.7%) vs.
      14/52 (26.9%); p=0.001. In patients who were bacteria-positive at both time
      points, mean (+/-1 SEM) load was significantly higher at exacerbation than stable
      state (108.5(+/-0.3) vs. 107.2(+/-0.5) cfu/ml), constituting a 20-fold increase
      (p=0.011). qPCR was more discriminatory at detecting typical bacteria than
      microbiological culture (prevalence 59.3% vs. 24.3%; p<0.001). At stable state,
      higher airway bacterial load correlated with more severe airflow limitation
      (FEV(1)%predicted) (r=-0.299; p=0.033) and higher inhaled corticosteroid dosage
      (r=0.382; p=0.008). Mean C-reactive protein was higher in bacterial-associated
      exacerbations (35.0 Vs 25.1 mg/L; p=0.032). CONCLUSIONS: Airway bacterial
      prevalence and load increase at COPD exacerbations and are an aetiological
      factor. qPCR is more discriminatory than culture, identifying higher airway
      bacterial prevalence. Exacerbations associated with bacterial detection showed a
      higher mean C-reactive protein level. In the stable state, airway bacterial load
      is related to more severe airflow limitation and higher inhaled corticosteroid
      dosage used.

PMID- 22863759
TI  - Enhanced radiosensitivity of non-small-cell lung cancer (NSCLC) by adenovirus
      mediated ING4 gene therapy.
AB  - Radiotherapy is the common treatment of choice for locally advanced lung cancer,
      but the radioresistance of lung cancer remains a significant therapeutic
      obstacle. We previously demonstrated that adenovirus-mediated inhibitor of growth
      4 (ING4) tumor suppressor gene delivery (AdVING4) can chemosensitize human
      hepatocarcinoma cells to anticancer drug cisplatin (CDDP). However, its
      radiosensitizing effects in cancer therapy are largely elusive. In the present
      study, we investigated the therapeutic efficacy of AdVING4 gene therapy combined
      with ionizing radiotherapy for SPC-A1 human non-small-cell lung cancer (NSCLC)
      cells in vitro and in vivo in athymic nude mice, and also elucidated its
      underlying mechanisms. We found that AdVING4 gene therapy plus radiotherapy
      induced synergistic tumor suppression and apoptosis in in vitro SPC-A1 human
      NSCLC cells and in vivo SPC-A1 xenografted tumors s.c. implanted in athymic nude
      mice. Mechanistically, AdVING4 combined with radiation resulted in a substantial
      upregulation of Bax, Fas, FasL and Cleaved Caspase-3, and downregulation of Bcl-2
      in SPC-A1 human NSCLC xenografted tumors. In addition, AdVING4 plus radiation
      synergistically reduced the tumor vessel CD34 expression and microvessel density
      (MVD) in vivo. Most importantly, AdVING4 potentially blocked the radiation
      induced enhancement of cyclooxygenase-2 and survivin radioresistant factors, and
      vascular endothelial growth factor and IL-8 proangiogenic factors. The enhanced
      antitumor effects elicited by AdVING4 plus radiotherapy were closely associated
      with the cooperative activation of intrinsic and extrinsic apoptotic pathways,
      and synergistic inhibition of tumor angiogenesis. Thus, our results suggested
      that AdVING4 combined with radiotherapy may be a feasible and effective strategy
      for treatment of radioresistant NSCLC and other cancers.

PMID- 22863760
TI  - Actin fringe is correlated with tip growth velocity of pollen tubes.

PMID- 22863761
TI  - Breast cancer sentinel node scintigraphy:  differences between imaging results 1
      and 2 h after injection.
AB  - INTRODUCTION: Timing of image acquisition in breast cancer sentinel node
      scintigraphy remains a subject of debate. Therefore, the performance of our
      protocol in which images are acquired 1 and 2 h after injection was evaluated.
      The results of sentinel node scintigraphy 1 and 2 h after injection were compared
      with regard to the sentinel lymph nodes visualized. METHODS: We studied 132
      patients who were consecutively referred for sentinel lymph node biopsy. 99mTc
      albumine nanocolloid (120 MBq) was injected peritumourally into patients with
      palpable tumours and intratumourally into patients with nonpalpable tumours. All
      scintigraphic images taken for the sentinel node procedure were evaluated. The
      number of sentinel nodes per anatomic localization and the interpretability of
      the images were scored. RESULTS: A total of 132 patients underwent sentinel node
      scintigraphy 1 h after injection. Of these, 117 patients also underwent sentinel
      node scintigraphy 2 h after injection. An axillary sentinel node was visualized
      in 79.5 and 95.7% of patients, respectively, 1 and 2 h after injection. In 20.5%
      of the patients the images acquired 1 h after injection did not show a sentinel
      node. Furthermore, in all procedures, the images 1 h after injection were of no
      added value to those acquired 2 h after injection. CONCLUSION: Scintigraphic
      imaging 2 h after a single peritumoural or intratumoural administration of about
      120 MBq 99mTc-albumine nanocolloid yields an axillary sentinel node in over 95%
      of cases. Imaging 1 h after injection is of no additional value and can be
      omitted.

PMID- 22863762
TI  - Noninvasive parametric blood flow imaging of head and neck tumours using [15O]H2O
      and PET/CT.
AB  - PURPOSE: The aim of this study was to develop a simple noninvasive method for
      measuring blood flow using [15O]H2O PET/CT for the head and neck area applicable
      in daily clinical practice. PATIENTS AND METHODS: Fifteen dynamic [15O]H2O PET
      emission scans with simultaneous online radioactivity measurements of radial
      arterial blood [Blood-input functions (IFs)] were performed. Two noninvasively
      obtained population-based input functions were calculated by averaging all Blood
      IF curves corrected for patients' body mass and injected dose [standardized
      uptake value (SUV)-IF] and for body surface area (BSA-IF) and injected dose.
      Parametric perfusion images were calculated for each set of IFs using a
      linearized two-compartment model, and values for several tissues were compared
      using Blood-IF as the gold standard. RESULTS: On comparing all tissues, the
      correlation between blood flow obtained with the invasive Blood-IF and both SUV
      IF and BSA-IF was significant (R2=0.785 with P<0.001 and R2=0.813 with P<0.001,
      respectively). In individual tissues, the performance of the two noninvasive
      methods was most reliable in resting muscle and slightly less reliable in tumour
      and cerebellar regions. In these two tissues, only BSA-IF showed a significant
      correlation with Blood-IF (R2=0.307 with P=0.032 in tumours and R2=0.398 with
      P<0.007 in the cerebellum). CONCLUSION: The BSA-based noninvasive method enables
      clinically relevant delineation between areas of low and high blood flow in
      tumours. The blood flow of low-perfusion tissues can be reliably quantified using
      either of the evaluated noninvasive methods.

PMID- 22863763
TI  - Mycobacterium bovis infection in livestock workers in Ibadan, Nigeria: evidence
      of occupational exposure.
AB  - SETTING: Bovine tuberculosis (TB) is endemic in the cattle population in Nigeria.
      Livestock workers are at risk of Mycobacterium bovis infection and unaware of
      their health status. OBJECTIVE: To determine the occurrence of pulmonary M. bovis
      infection among livestock  workers. DESIGN: A cross-sectional study of livestock
      traders was conducted for TB through screening of sputum samples using a simple
      random sampling method coupled with oral interview on the assumption of sub
      clinical pulmonary TB infection. Specimens were cultured, and the isolates
      analysed  using molecular typing techniques. RESULTS: Overall, 10% (7/70) of the
      livestock traders had a positive culture indicative of M. tuberculosis  complex,
      which were differentiated into M. bovis (n = 2) and M. tuberculosis (n = 5) using
      deletion typing. Further  spoligotyping analyses of the M. bovis and two
      available M. tuberculosis isolates classified the strains as SB1432 and SB09444
      and LAM_10 CAM and T1 using respectively www.mbovis.org and spotclust databases.
      Prolonged cough and >3 years in the livestock trade were risk factors  for
      infection. CONCLUSION: We confirm that there is undetected pulmonary M. bovis
      infection among livestock traders in Nigeria. Further studies on the role of
      occupationally exposed workers in the transmission of M. bovis infection to the
      larger community are required.

PMID- 22863764
TI  - Predicted effects of treatment for HCV infection vary among European countries.
AB  - BACKGROUND & AIMS: The dynamics of hepatitis C virus (HCV) infection, as well as
      screening practices and access to therapy, vary among European countries. It is
      important to determine the magnitude of the effects of such differences on
      incidence and mortality of infection. We compared the dynamics of infection and
      screening and treatment practices among Belgium, France, Germany, Italy, Spain,
      and the United Kingdom. We also assessed the effects of treatment with pegylated
      interferon and additional effects of triple therapy with protease inhibitors.
      METHODS: We created a country-specific Markov model of HCV progression based on
      published epidemiologic data (on HCV prevalence, screening, genotype, alcohol
      consumption among patients, and treatments) and reports of competitive and
      hepatocellular carcinoma mortality for the 6 countries. The model was used to
      predict the incidence of HCV-related cirrhosis and its mortality until 2021 for
      each country. RESULTS: From 2002 to 2011, antiviral therapy reduced the
      cumulative incidence of cirrhosis by 7.1% and deaths by 3.4% overall. Reductions
      in incidence and mortality values ranged from 4.0% and 1.9%, respectively, in
      Italy to 16.3% and 9.0%, respectively, in France. From 2012 to 2021, antiviral
      treatment of patients with HCV genotype 1 infection that includes protease
      inhibitor-based triple therapy will reduce the cumulative incidence of cirrhosis
      by 17.7% and mortality by 9.7% overall. The smallest reduction is predicted for
      Italy (incidence reduced by 10.1% and mortality by 5.4%) and the highest is for
      France (reductions of 34.3% and 20.7%, respectively). CONCLUSIONS: Although HCV
      infection is treated with the same therapies in different countries, the effects
      of the therapies on morbidity and mortality vary significantly. In addition to
      common guidelines that are based on virologic response-guided therapy, there is a
      need for public health policies based on population-guided therapy.

PMID- 22863765
TI  - Lymphotoxin beta receptor signaling promotes development of autoimmune
      pancreatitis.
AB  - BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of autoimmune
      pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic
      pancreatitis. Current treatment options are limited and disease relapse is
      frequent. We investigated factors that contribute to the development of AIP and
      new therapeutic strategies. METHODS: We used quantitative polymerase chain
      reaction, immunohistochemical, and enzyme-linked immunosorbent analyses to
      measure the expression of cytokines and chemokines in tissue and serum samples
      from patients with and without AIP. We created a mouse model of human AIP by
      overexpressing lymphotoxin (LT)alpha and beta specifically in acinar cells (Ela1
      LTab mice). RESULTS: Messenger RNA levels of LTalpha and beta were increased in
      pancreatic tissues from patients with AIP, compared with controls, and expression
      of chemokines (CXCL13, CCL19, CCL21, CCL1, and B-cell-activating factor) was
      increased in pancreatic and serum samples from patients. Up-regulation of these
      factors was not affected by corticosteroid treatment. Acinar-specific
      overexpression of LTalphabeta (Ela1-LTalphabeta) in mice led to an autoimmune
      disorder with various features of AIP. Chronic inflammation developed only in the
      pancreas but was sufficient to cause systemic autoimmunity. Acinar-specific
      overexpression of LTalphabeta did not cause autoimmunity in mice without
      lymphocytes (Ela1-LTab/Rag1(-/-)); moreover, lack of proinflammatory monocytes
      (Ela1-LTab/Ccr2(-/-)) failed to prevent AIP but prevented early pancreatic tissue
      damage. Administration of corticosteroids reduced pancreatitis but did not affect
      production of autoantibodies, such as antipancreatic secretory trypsin inhibitor
      in Ela1-LTab mice. In contrast, inhibition of LTbetaR signaling reduced chemokine
      expression, renal immune-complex deposition, and features of AIP in Ela1-LTab
      mice. CONCLUSIONS: Overexpression of LTalphabeta specifically in acinar cells of
      mice causes features of AIP. Reagents that neutralize LTbetaR ligands might be
      used to treat patients with AIP.

PMID- 22863766
TI  - An R package suite for microarray meta-analysis in quality control,
      differentially expressed gene analysis and pathway enrichment detection.
AB  - SUMMARY: With the rapid advances and prevalence of high-throughput genomic
      technologies, integrating information of multiple relevant genomic studies has
      brought new challenges. Microarray meta-analysis has become a frequently used
      tool in biomedical research. Little effort, however, has been made to develop a
      systematic pipeline and user-friendly software. In this article, we present
      MetaOmics, a suite of three R packages MetaQC, MetaDE and MetaPath, for quality
      control, differentially expressed gene identification and enriched pathway
      detection for microarray meta-analysis. MetaQC provides a quantitative and
      objective tool to assist study inclusion/exclusion criteria for meta-analysis.
      MetaDE and MetaPath were developed for candidate marker and pathway detection,
      which provide choices of marker detection, meta-analysis and pathway analysis
      methods. The system allows flexible input of experimental data, clinical outcome
      (case-control, multi-class, continuous or survival) and pathway databases. It
      allows missing values in experimental data and utilizes multi-core parallel
      computing for fast implementation. It generates informative summary output and
      visualization plots, operates on different operation systems and can be expanded
      to include new algorithms or combine different types of genomic data. This
      software suite provides a comprehensive tool to conveniently implement and
      compare various genomic meta-analysis pipelines. AVAILABILITY:
      http://www.biostat.pitt.edu/bioinfo/software.htm CONTACT: ctseng@pitt.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22863768
TI  - Exercise: applications to childhood ADHD.
AB  - ADHD is the most common neurobehavioral disorder of childhood, presenting with
      pervasive and impairing symptoms of inattention, hyperactivity, impulsivity, or a
      combination. The leading hypothesis of the underlying physiology of this disorder
      of inattention and/or hyperactivity-impulsivity is based on catecholamine
      dysfunction. Pharmacotherapy research indicates that psychostimulants, which are
      catecholamine agonists, show the greatest efficacy for treating the core symptoms
      of ADHD. Exercise affects the same dopaminergic and noradrenergic systems that
      stimulant medications target and is a stressor, which elicits measurable
      physiological changes. The magnitude of these peripheral alterations is posited
      as a potential biomarker of ADHD. The hypothesis that exercise training alters
      the underlying physiology present in ADHD and other medical conditions as well as
      conceptual issues behind its potential clinical utility is reviewed.

PMID- 22863767
TI  - Identifying multi-layer gene regulatory modules from multi-dimensional genomic
      data.
AB  - MOTIVATION: Eukaryotic gene expression (GE) is subjected to precisely coordinated
      multi-layer controls, across the levels of epigenetic, transcriptional and post
      transcriptional regulations. Recently, the emerging multi-dimensional genomic
      dataset has provided unprecedented opportunities to study the cross-layer
      regulatory interplay. In these datasets, the same set of samples is profiled on
      several layers of genomic activities, e.g. copy number variation (CNV), DNA
      methylation (DM), GE and microRNA expression (ME). However, suitable analysis
      methods for such data are currently sparse. RESULTS: In this article, we
      introduced a sparse Multi-Block Partial Least Squares (sMBPLS) regression method
      to identify multi-dimensional regulatory modules from this new type of data. A
      multi-dimensional regulatory module contains sets of regulatory factors from
      different layers that are likely to jointly contribute to a local 'gene
      expression factory'. We demonstrated the performance of our method on the
      simulated data as well as on The Cancer Genomic Atlas Ovarian Cancer datasets
      including the CNV, DM, ME and GE data measured on 230 samples. We showed that
      majority of identified modules have significant functional and transcriptional
      enrichment, higher than that observed in modules identified using only a single
      type of genomic data. Our network analysis of the modules revealed that the CNV,
      DM and microRNA can have coupled impact on expression of important oncogenes and
      tumor suppressor genes. AVAILABILITY AND IMPLEMENTATION: The source code
      implemented by MATLAB is freely available at: http://zhoulab.usc.edu/sMBPLS/.
      CONTACT: xjzhou@usc.edu SUPPLEMENTARY INFORMATION: Supplementary material are
      available at Bioinformatics online.

PMID- 22863769
TI  - Characteristics of Children With ADHD and Comorbid Anxiety.
AB  - OBJECTIVE: The following comorbid subgroups of ADHD have been proposed: ADHD
      Only, ADHD + anxiety disorders (ANX), ADHD + oppositional defiant
      disorder/conduct disorder (ODD/CD), and ADHD + ODD/CD + ANX. The current study
      examined a subset of these groups. METHOD: A total of 134 children and
      adolescents (M age = 9.92; range = 6-17) from a clinic-referred sample (n = 407)
      were grouped based on a semistructured diagnostic interview: ADHD only (n = 41),
      ADHD + ANX (n = 31), and ANX Only (n = 62). RESULTS: Findings supported greater
      parent-reported anxiety symptoms in anxiety groups, and greater parent- and
      teacher-reported attention problems in ADHD groups. ADHD groups performed worse
      on a continuous performance test, whereas ADHD + ANX performed worse on working
      memory than ADHD Only. ADHD + ANX reported more physical anxiety symptoms than
      ADHD Only. CONCLUSION: Comorbid anxiety should be considered in ADHD assessment
      and treatment.

PMID- 22863770
TI  - Atlas of human embryology: from oocytes to preimplantation embryos. Preface.

PMID- 22863772
TI  - HLA class II susceptibility to cervical cancer among Tunisian women.
AB  - The variability in host immunogenetic background, especially in human major
      histocompatibilty genes, has been shown to influence the susceptibility to human
      papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case
      control study in Tunisian women to examine the effect of genetic variation in HLA
      class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell
      carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers
      technique. The data revealed significant positive and negative associations,
      suggesting either predisposing or protective effects of these genes in the
      disease outcome. DRB1*15, alone or linked to DQB1*06, was associated with a 2.7-
      and 3.5-fold increase in risk for ICC, respectively. DRB1*13-DQB1*03 showed a
      similar 3.5 risk effect. Concerning SCC, we observed a relatively higher, about
      1.2 times more, risk effect for these genetic markers. In contrast, only one
      haplotype - DRB1*13-DQB1*06 - provides evidence for a weak protection (about 0.3
      fold reduction) of ICC and SCC. In conclusion, we suggest that HLA class II
      polymorphisms are involved in the genetic susceptibility to cervical cancer in
      Tunisian women.

PMID- 22863773
TI  - Generation of DNA single-strand displacement by compromised nucleotide excision
      repair.
AB  - Nucleotide excision repair (NER) is a precisely coordinated process essential to
      avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we
      investigate the mechanistic details and effects of the NER machinery when it is
      compromised by a pathologically significant mutation in a subunit of the
      repair/transcription factor TFIIH, namely XPD. In contrast to previous studies,
      we find that no single- or double-strand DNA breaks are produced at early time
      points after UV irradiation of cells bearing a specific XPD mutation, despite the
      presence of a clear histone H2AX phosphorylation (gammaH2AX) signal in the UV
      exposed areas. We show that the observed gammaH2AX signal can be explained by the
      presence of longer single-strand gaps possibly generated by strand displacement.
      Our in vivo measurements also indicate a strongly reduced TFIIH-XPG binding that
      could promote single-strand displacement at the site of UV lesions. This finding
      not only highlights the crucial role of XPG's interactions with TFIIH for proper
      NER, but also sheds new light on how a faulty DNA repair process can induce
      extreme genomic instability in human patients.

PMID- 22863774
TI  - The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I mRNA
      degradation.
AB  - RNA-binding E3 ubiquitin ligases were recently identified, though their function
      remains unclear. While studying the regulation of the MHC class I (MHC-I)
      pathway, we here characterize a novel role for ubiquitin in mRNA degradation. MHC
      I molecules provide ligands for both cytotoxic T-lymphocytes as well as natural
      killer (NK) cells, and play a central role in innate and adaptive immunity. MHC-I
      cell-surface expression is closely monitored by NK cells, whose killer
      immunoglobulin-like receptors encode MHC-I-specific activatory and inhibitory
      receptors, implying that MHC-I expression needs to be tightly regulated. In a
      functional siRNA ubiquitome screen we identified MEX-3C, a novel RNA-binding
      ubiquitin E3 ligase, as responsible for the post-transcriptional, allotype
      specific regulation of MHC-I. MEX-3C binds the 3'UTR of HLA-A2 mRNA, inducing its
      RING-dependent degradation. The RING domain of MEX-3C is not required for HLA-A2
      cell-surface downregulation, but regulates the degradation of HLA-A2 mRNA. We
      have therefore uncovered a novel post-transcriptional pathway for regulation of
      HLA-A allotypes and provide a link between ubiquitination and mRNA degradation.

PMID- 22863775
TI  - Human CST promotes telomere duplex replication and general replication restart
      after fork stalling.
AB  - Mammalian CST (CTC1-STN1-TEN1) associates with telomeres and depletion of CTC1 or
      STN1 causes telomere defects. However, the function of mammalian CST remains
      poorly understood. We show here that depletion of CST subunits leads to both
      telomeric and non-telomeric phenotypes associated with DNA replication defects.
      Stable knockdown of CTC1 or STN1 increases the incidence of anaphase bridges and
      multi-telomeric signals, indicating genomic and telomeric instability. STN1
      knockdown also delays replication through the telomere indicating a role in
      replication fork passage through this natural barrier. Furthermore, we find that
      STN1 plays a novel role in genome-wide replication restart after hydroxyurea (HU)
      induced replication fork stalling. STN1 depletion leads to reduced EdU
      incorporation after HU release. However, most forks rapidly resume replication,
      indicating replisome integrity is largely intact and STN1 depletion has little
      effect on fork restart. Instead, STN1 depletion leads to a decrease in new origin
      firing. Our findings suggest that CST rescues stalled replication forks during
      conditions of replication stress, such as those found at natural replication
      barriers, likely by facilitating dormant origin firing.

PMID- 22863776
TI  - Multivalent di-nucleosome recognition enables the Rpd3S histone deacetylase
      complex to tolerate decreased H3K36 methylation levels.
AB  - The Rpd3S histone deacetylase complex represses cryptic transcription initiation
      within coding regions by maintaining the hypo-acetylated state of transcribed
      chromatin. Rpd3S recognizes methylation of histone H3 at lysine 36 (H3K36me),
      which is required for its deacetylation activity. Rpd3S is able to function over
      a wide range of H3K36me levels, making this a unique system to examine how
      chromatin regulators tolerate the reduction of their recognition signal. Here, we
      demonstrated that Rpd3S makes histone modification-independent contacts with
      nucleosomes, and that Rpd3S prefers di-nucleosome templates since two binding
      surfaces can be readily accessed simultaneously. Importantly, this multivalent
      mode of interaction across two linked nucleosomes allows Rpd3S to tolerate a two
      fold intramolecular reduction of H3K36me. Our data suggest that chromatin
      regulators utilize an intrinsic di-nucleosome-recognition mechanism to prevent
      compromised function when their primary recognition modifications are diluted.

PMID- 22863777
TI  - The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR
      RING domain and the unique LDD extension.
AB  - Activation of the NF-kappaB pathway requires the formation of Met1-linked
      'linear' ubiquitin chains on NEMO, which is catalysed by the Linear Ubiquitin
      Chain Assembly Complex (LUBAC) E3 consisting of HOIP, HOIL-1L and Sharpin. Here,
      we show that both LUBAC catalytic activity and LUBAC specificity for linear
      ubiquitin chain formation are embedded within the RING-IBR-RING (RBR) ubiquitin
      ligase subunit HOIP. Linear ubiquitin chain formation by HOIP proceeds via a two
      step mechanism involving both RING and HECT E3-type activities. RING1-IBR
      catalyses the transfer of ubiquitin from the E2 onto RING2, to transiently form a
      HECT-like covalent thioester intermediate. Next, the ubiquitin is transferred
      from HOIP onto the N-terminus of a target ubiquitin. This transfer is facilitated
      by a unique region in the C-terminus of HOIP that we termed 'Linear ubiquitin
      chain Determining Domain' (LDD), which may coordinate the acceptor ubiquitin.
      Consistent with this mechanism, the RING2-LDD region was found to be important
      for NF-kappaB activation in cellular assays. These data show how HOIP combines a
      general RBR ubiquitin ligase mechanism with unique, LDD-dependent specificity for
      producing linear ubiquitin chains.

PMID- 22863778
TI  - Holliday junction affinity of the base excision repair factor Endo III
      contributes to cholera toxin phage integration.
AB  - Toxigenic conversion of Vibrio cholerae bacteria results from the integration of
      a filamentous phage, CTX phage. Integration is driven by the bacterial Xer
      recombinases, which catalyse the exchange of a single pair of strands between the
      phage single-stranded DNA and the host double-stranded DNA genomes; replication
      is thought to convert the resulting pseudo-Holliday junction (HJ) intermediate
      into the final recombination product. The natural tendency of the Xer
      recombinases to recycle HJ intermediates back into substrate should thwart this
      integration strategy, which prompted a search for additional co-factors aiding
      directionality of the process. Here, we show that Endo III, a ubiquitous base
      excision repair enzyme, facilitates CTX phage-integration in vivo. In vitro, we
      show that it prevents futile Xer recombination cycles by impeding new rounds of
      strand exchanges once the pseudo-HJ is formed. We further demonstrate that this
      activity relies on the unexpected ability of Endo III to bind to HJs even in the
      absence of the recombinases. These results explain how tandem copies of the phage
      genome can be created, which is crucial for subsequent virion production.

PMID- 22863779
TI  - CSR-1 RNAi pathway positively regulates histone expression in C. elegans.
AB  - Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many
      organisms, including mammals. In C. elegans, depletion of germline-enriched endo
      siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and
      defects in chromosome segregation in early embryos. We discovered that knockdown
      of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer
      related helicase drh-3, leads to defects in histone mRNA processing, resulting in
      severe depletion of core histone proteins. The maturation of replication
      dependent histone mRNAs, unlike that of other mRNAs, requires processing of their
      3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is
      lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match
      histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1
      directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'
      O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the
      dosage of histone genes rescues the lethality associated with depletion of CSR-1
      and EGO-1. These results support a positive and direct effect of RNAi on histone
      gene expression.

PMID- 22863781
TI  - Nanosurface design of dental implants for improved cell growth and function.
AB  - A  strategy was proposed for the topological design of dental implants based on
      an in vitro survey of optimized nanodot structures. An in vitro survey was
      performed using nanodot arrays with dot diameters ranging from 10 to 200 nm. MG63
      osteoblasts were seeded on nanodot arrays and cultured for 3 days. Cell number,
      percentage undergoing apoptotic-like cell death, cell adhesion and cytoskeletal
      organization were evaluated. Nanodots with a diameter of approximately 50 nm
      enhanced cell number by 44%, minimized apoptotic-like cell death to 2.7%,
      promoted a 30% increase in microfilament bundles and maximized cell adhesion with
      a 73% increase in focal adhesions. An enhancement of about 50% in mineralization
      was observed, determined by von Kossa staining and by Alizarin Red S staining.
      Therefore, we provide a complete range of nanosurfaces for growing osteoblasts to
      discriminate their nanoscale environment. Nanodot arrays present an opportunity
      to positively and negatively modulate cell behavior and maturation. Our results
      suggest a topological approach which is beneficial for the design of dental
      implants.

PMID- 22863780
TI  - DSCR1 interacts with FMRP and is required for spine morphogenesis and local
      protein synthesis.
AB  - Most common genetic factors known to cause intellectual disability are Down
      syndrome and Fragile X syndrome. However, the underlying cellular and molecular
      mechanisms of intellectual disability remain unclear. Recently, dendritic spine
      dysmorphogenesis and impaired local protein synthesis are posited to contribute
      to the cellular mechanisms of intellectual disability. Here, we show that Down
      syndrome critical region1 (DSCR1) interacts with Fragile X mental retardation
      protein (FMRP) and regulates both dendritic spine morphogenesis and local protein
      synthesis. Interestingly, decreasing the level of FMRP restores the DSCR1-induced
      changes in dendritic spine morphology. Our results imply that DSCR1 is a novel
      regulator of FMRP and that Fragile X syndrome and Down syndrome may share
      disturbances in common pathways that regulate dendritic spine morphology and
      local protein synthesis.

PMID- 22863782
TI  - Serum complement C3 predicts renal arteriolosclerosis in non-diabetic chronic
      kidney disease.
AB  - AIM: Complement C3 (C3) is one of the major mediators of inflammation. Serum C3
      has been shown to be correlated with the presence of atherosclerosis. We examined
      whether the serum C3 level might be correlated with the severity of renal
      arteriolosclerosis in patients with chronic kidney disease (CKD). METHODS: Non
      diabetic CKD (stages 1-3) patients who underwent renal biopsy were enrolled in
      this study. Renal arteriolosclerosis was defined by the presence of hyaline
      changes and vessel wall thickening in the renal biopsy specimens. We examined
      whether the serum C3 level might be correlated with the severity of renal
      arteriolosclerosis in CKD patients. RESULTS: A total of 208 CKD patients (age
      36.0+/-13.6 years; 94 male) who underwent renal biopsy were included. Univariate
      analysis showed that the serum C3 level was positively correlated with age, body
      mass index, blood pressure and the serum triglyceride, LDL cholesterol and CRP
      (p<0.001). The serum C3 level was also inversely correlated with serum HDL
      cholesterol (p<0.001). Multiple regression analysis identified that the serum C3
      (p=0.043) as well as age (p<0.001), serum uric acid (p=0.009) and eGFR (p= 0.025)
      were independently associated with the severity of renal arteriolosclerosis.
      CONCLUSION: Our results suggest that the serum C3 level is a reliable marker of
      renal arteriolosclerosis. Components of metabolic syndrome were also correlated
      with the serum C3 level. Inflammation or metabolic syndrome may contribute to CKD
      through influencing the rate of progression of renal arteriolosclerosis.

PMID- 22863783
TI  - Systematic analysis of risk factors for coronary heart disease in Japanese
      patients with type 2 diabetes: a matched case-control study.
AB  - AIM: To identify predictors of coronary heart disease (CHD) in Japanese patients
      with type 2 diabetes (T2DM). METHODS: A matched case-control study was performed
      using 800 patients with T2DM admitted for treatment of hyperglycemia from January
      2002 to June 2010. Cases comprised 16 patients who had developed acute myocardial
      infarction and/or received a coronary artery bypass by June 2010, and controls
      comprised 48 age- and sex-matched patients without CHD events. The mean age,
      glycated hemoglobin (HbA1c), and body mass index (BMI) were 61.5 yrs, 9.7% and
      24.4 kg/m(2), respectively. The relationship of baseline variables, including
      lipid values, HbA1c, BMI, blood pressure, fasting blood sugar, 2h-post-breakfast
      blood sugar, delta blood sugar(0-2h), urinary albumin excretion, estimated
      glomerular filtration rate and treatment modalities
      (insulin/sulfonylurea/biguanide), to CHD development was analyzed by conditional
      logistic regression analysis. RESULTS: Total cholesterol (TC) (OR 2.35, 95%CI
      1.11-4.98, p=0.03), non-HDL-cholesterol (OR 3.07, 95%CI 1.33-7.10, p=0.009), LDL
      cholesterol (OR 2.84, 95%CI 1.24-6.51, p=0.01), non-HDL-cholesterol/HDL
      cholesterol (OR 2.07, 95%CI 1.10-3.90, p=0.02) and LDL-cholesterol/ HDL
      cholesterol (OR 2.74, 95%CI 1.22-6.15, p=0.01) were significantly related to CHD.
      Fold risk increment per 1-SD increase in basal TC, non-HDL-cholesterol, LDL
      cholesterol, non-HDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL
      cholesterol was 2.33, 2.89, 2.52, 2.37 and 2.60, respectively. Only non-HDL
      cholesterol was an independent risk factor. From the receiver operating
      characteristic curve, 3.89 mmol/L non-HDL-C was the best cutoff value. None of
      the non-lipid variables were significantly related to CHD. CONCLUSION: Non-HDL
      cholesterol was the most dominant predictor of the development of CHD in Japanese
      patients with T2DM.

PMID- 22863784
TI  - Effect of advanced glycation end products on lectin-like oxidized low density
      lipoprotein receptor-1 expression in endothelial cells.
AB  - AIM: Lectin-like oxidized LDL receptor-1 (LOX-1) is a class E oxidized LDL
      specific scavenger receptor that recognizes multiple ligands. Advanced glycation
      end products (AGEs) have been recently identified as other ligands to LOX-1 and
      shown to increase LOX-1 expressions in diabetes; therefore, we investigated the
      underlying mechanism involved. METHODS: Confluent human aortic endothelial cells
      were treated with a fixed concentration of AGE-BSA or BSA as a control in the
      presence or absence of either antibody of the receptor for advanced glycation end
      products, mammalian target of rapamycin (mTOR) inhibitor rapamycin, NF-kB
      inhibitor, phosphoinositide 3-kinases (PI3K) inhibitor or anti-diabetic drug
      metformin. After stimulation, cells were lysed and Western blot protein
      expression on LOX-1, rapamycin-insensitive companion of mTOR (RICTOR), the
      phosphorylation status of p-mTOR, p-P70S6 kinase and p-Akt were determined.
      RESULTS: AGEs induced LOX-1 expression in endothelial cells. Pretreatment either
      with anti-RAGE antibody or LY294002 prior to AGE-BSA decreases LOX-1 and p-mTOR
      expressions. Incubating endothelial cells with AGE-BSA in the presence of
      rapamycin down-regulated the protein expression-level of p-mTOR by 41% (p<0.05)
      and LOX-1 expression by 61.5% (p<0.01). Knockdown of RICTOR by RNA silencing
      showed a 41.5% (p<0.01) and 71.2% (p<0.01) reduction in LOX-1 and p-Akt
      expressions, respectively. Preincubation of endothelial cells with AGE-BSA and
      metformin, an anti-diabetic drug known to have an mTOR inhibition effect,
      significantly reduced AGE-stimulated LOX-1 expression. CONCLUSION: Our results
      indicated that LOX-1 up-regulation induced by AGE-BSA was a receptor mediated
      through RAGE and is via the PI3K/PDK1/mTORC2 pathway. Metformincan reduce AGE
      stimulated LOX-1 expression in endothelial cells in vitro.

PMID- 22863785
TI  - Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell
      death and exhaustion.
AB  - T cell immunoglobulin and mucin domain-containing 3 (Tim-3) is an inhibitory
      receptor that is expressed on exhausted T cells during infection with HIV-1 and
      hepatitis C virus. By contrast, Tim-3 expression and function are defective in
      multiple human autoimmune diseases. However, the molecular mechanisms modulating
      Tim-3 function are not well understood. Here we show that human leukocyte antigen
      B (HLA-B)-associated transcript 3 (Bat3) binds to, and represses the function of,
      Tim-3. Bat3 protects T helper type 1 (TH1) cells from galectin-9-mediated cell
      death and promotes both proliferation and proinflammatory cytokine production.
      Bat3-deficient T cells have elevated expression of exhaustion-associated
      molecules such as Tim-3, Lag3, Prdm1 and Pbx3, and Bat3 knockdown in myelin
      antigen-specific CD4+ T cells markedly inhibits the development of experimental
      autoimmune encephalomyelitis while promoting the expansion of a dysfunctional Tim
      3hi, interferon-gamma (IFN-gamma)loCD4+ cell population. Furthermore, expression
      of Bat3 is reduced in exhausted Tim-3+ T cells from mouse tumors and HIV-1
      infected individuals. These data indicate that Bat3 acts as an inhibitor of Tim-3
      dependent exhaustion and cell death. Bat3 may thus represent a viable therapeutic
      target in autoimmune disorders, chronic infections and cancers.

PMID- 22863786
TI  - Treatment-induced damage to the tumor microenvironment promotes prostate cancer
      therapy resistance through WNT16B.
AB  - Acquired resistance to anticancer treatments is a substantial barrier to reducing
      the morbidity and mortality that is attributable to malignant tumors. Components
      of tissue microenvironments are recognized to profoundly influence cellular
      phenotypes, including susceptibilities to toxic insults. Using a genome-wide
      analysis of transcriptional responses to genotoxic stress induced by cancer
      therapeutics, we identified a spectrum of secreted proteins derived from the
      tumor microenvironment that includes the Wnt family member wingless-type MMTV
      integration site family member 16B (WNT16B). We determined that WNT16B expression
      is regulated by nuclear factor of kappa light polypeptide gene enhancer in B
      cells 1 (NF-kappaB) after DNA damage and subsequently signals in a paracrine
      manner to activate the canonical Wnt program in tumor cells. The expression of
      WNT16B in the prostate tumor microenvironment attenuated the effects of cytotoxic
      chemotherapy in vivo, promoting tumor cell survival and disease progression.
      These results delineate a mechanism by which genotoxic therapies given in a
      cyclical manner can enhance subsequent treatment resistance through cell
      nonautonomous effects that are contributed by the tumor microenvironment.

PMID- 22863787
TI  - Neutrophils mediate insulin resistance in mice fed a high-fat diet through
      secreted elastase.
AB  - Chronic low-grade adipose tissue and liver inflammation is a major cause of
      systemic insulin resistance and is a key component of the low degree of insulin
      sensitivity that exists in obesity and type 2 diabetes. Immune cells, such as
      macrophages, T cells, B cells, mast cells and eosinophils, have all been
      implicated as having a role in this process. Neutrophils are typically the first
      immune cells to respond to inflammation and can exacerbate the chronic
      inflammatory state by helping to recruit macrophages and by interacting with
      antigen-presenting cells. Neutrophils secrete several proteases, one of which is
      neutrophil elastase, which can promote inflammatory responses in several disease
      models. Here we show that treatment of hepatocytes with neutrophil elastase
      causes cellular insulin resistance and that deletion of neutrophil elastase in
      high-fat-diet-induced obese (DIO) mice leads to less tissue inflammation that is
      associated with lower adipose tissue neutrophil and macrophage content. These
      changes are accompanied by improved glucose tolerance and increased insulin
      sensitivity. Taken together, we show that neutrophils can be added to the
      extensive repertoire of immune cells that participate in inflammation-induced
      metabolic disease.

PMID- 22863789
TI  - Patient awareness of binocular central scotoma in age-related macular
      degeneration.
AB  - PURPOSE: To assess whether age-related macular degeneration (AMD) patients are
      aware of binocular central visual field defects. METHODS: One hundred fifty-three
      consecutive AMD patients in their initial low-vision rehabilitation evaluation
      were immediately asked at the beginning of their visit (1) whether they were able
      to see any blind spots or defects in their field of vision and (2) whether they
      had any evidence or experiences that led them to believe that they had defects in
      their field of vision. They then had their vision assessed by binocular central
      visual field testing using the California Central Visual Field Test, binocular
      reading performance evaluated using the Smith-Kettlewell Reading Test (SK Read)
      and MN Read charts, and visual acuity measured using the ETDRS chart at 1 meter.
      Mean diameters of the scotomas with borders near fixation were noted. RESULTS:
      Visual acuity median was 20/253 (range 20/40 to hand movements). Binocular
      scotomas were present in 88% of patients (66% had dense scotoma). Of patients
      with binocular scotomas, 56% were totally unaware of their presence, even with
      dense scotomas measuring up to 30 degrees  in diameter; 1.5% could fleetingly see
      a defect in their visual field on waking; and 44% related experiences of things
      "disappearing" on them. The median and range of scotoma diameters for those
      unaware vs. those with some awareness of their scotomas were comparable. There
      was no significant relationship of awareness of the scotoma with age, acuity,
      scotoma size, density, or duration of onset. Awareness of scotoma was associated
      with fewer errors on the SK Read (p < 0.01). CONCLUSIONS: Low vision clinicians
      cannot depend on patients to report the presence of significant scotomas; thus,
      appropriate testing must be performed. Presence of scotomas decreased reading
      accuracy, but some awareness of the scotomas had a tendency to improve accuracy.
      The value of rehabilitation programs aimed at increasing patient awareness of
      their scotomas may be supported by this evidence.

PMID- 22863790
TI  - Impact of pediatric vision impairment on daily life:  results of focus groups.
AB  - PURPOSE: To identify through focus groups of visually impaired children and their
      parents, relevant content for a vision-targeted health-related quality of life
      (HRQoL) questionnaire designed for children aged 6 to 12 years. METHODS: Six
      focus groups of children with vision impairment aged 6 to 12 years and six focus
      groups of their parents were conducted by trained facilitators using a guided
      script. Sessions were recorded, transcribed, and coded as per a standardized
      protocol for content analysis. Comments were placed in thematic categories and
      each was coded as positive, negative, or neutral. RESULTS: Twenty-four children
      (mean age: 9.4 years) with vision impairment from a variety of causes and 23
      parents participated in the study. The child focus groups generated 1,163
      comments, of which 52% (n = 599) were negative, 12% (n = 138) were neutral, and
      37% (n = 426) were positive. The three most common topical areas among children
      were: glasses and adaptive equipment (18%), psychosocial (14%), and school (14%).
      The parent focus groups generated 1952 comments of which 46% (n = 895) were
      negative, 16% (n = 323) were neutral, and 38% (n = 734) were positive. The three
      most common topical areas among parents were: school (21%), expectations or
      frustrations (14%), and psychosocial (13%). CONCLUSIONS: Pediatric vision
      impairment has significant effects on HRQoL, as reported by children with vision
      impairment and their parents in their own words. These findings will provide the
      content to guide construction of a survey instrument to assess vision-specific,
      HRQoL in children with vision impairment.

PMID- 22863791
TI  - Driving with bioptic telescopes:  organizing a research agenda.
AB  - Being a licensed driver in the United States and many other countries facilitates
      health and well-being. Based on the vision standards in most states, individuals
      with worse than 20/40 visual acuity who desire licensure are denied through the
      usual licensure application process. However, >40 states have bioptic telescope
      licensing programs where applicants can gain licensure contingent on meeting
      specific requirements. Despite the existence of the bioptic telescope and these
      licensing programs since the 1970s, there has been little rigorous scientific
      study of this topic. Here, I offer an organizing perspective for a research
      agenda on driving with bioptic telescopes, with the long-term practical goal
      being to provide an evidence basis for licensure policies and training programs.

PMID- 22863792
TI  - Seeing steps and ramps with simulated low acuity:  impact of texture and
      locomotion.
AB  - PURPOSE: Detecting and recognizing steps and ramps is an important component of
      the visual accessibility of public spaces for people with impaired vision. The
      present study, which is part of a larger program of research on visual
      accessibility, investigated the impact of two factors that may facilitate the
      recognition of steps and ramps during low-acuity viewing. Visual texture on the
      ground plane is an environmental factor that improves judgments of surface
      distance and slant. Locomotion (walking) is common during observations of a
      layout, and may generate visual motion cues that enhance the recognition of steps
      and ramps. METHODS: In two experiments, normally sighted subjects viewed the
      targets monocularly through blur goggles that reduced acuity to either
      approximately 20/150 (mild blur) or 20/880 Snellen (severe blur). The subjects
      judged whether a step, ramp, or neither was present ahead on a sidewalk. In the
      texture experiment, subjects viewed steps and ramps on a surface with a coarse
      black-and-white checkerboard pattern. In the locomotion experiment, subjects
      walked along the sidewalk toward the target before making judgments. RESULTS:
      Surprisingly, performance was lower with the textured surface than with a uniform
      surface, perhaps because the texture masked visual cues necessary for target
      recognition. Subjects performed better in walking trials than in stationary
      trials, possibly because they were able to take advantage of visual cues that
      were only present during motion. CONCLUSIONS: We conclude that under conditions
      of simulated low acuity, large high-contrast texture elements can hinder the
      recognition of steps and ramps, whereas locomotion enhances recognition.

PMID- 22863788
TI  - A comparison of epithelial-to-mesenchymal transition and re-epithelialization.
AB  - Wound healing and cancer metastasis share a common starting point, namely, a
      change in the phenotype of some cells from stationary to motile. The term,
      epithelial-to-mesenchymal transition (EMT) describes the changes in molecular
      biology and cellular physiology that allow a cell to transition from a sedentary
      cell to a motile cell, a process that is relevant not only for cancer and
      regeneration, but also for normal development of multicellular organisms. The
      present review compares the similarities and differences in cellular response at
      the molecular level as tumor cells enter EMT or as keratinocytes begin the
      process of re-epithelialization of a wound. Looking toward clinical interventions
      that might modulate these processes, the mechanisms and outcomes of current and
      potential therapies are reviewed for both anti-cancer and pro-wound healing
      treatments related to the pathways that are central to EMT. Taken together, the
      comparison of re-epithelialization and tumor EMT serves as a starting point for
      the development of therapies that can selectively modulate different forms of
      EMT.

PMID- 22863793
TI  - Effects of contour enhancement on low-vision preference and visual search.
AB  - PURPOSE: To determine whether image enhancement improves visual search
      performance and whether enhanced images were also preferred by subjects with
      vision impairment. METHODS: Subjects (n = 24) with vision impairment (vision:
      20/52 to 20/240) completed visual search and preference tasks for 150 static
      images that were enhanced to increase object contours' visual saliency. Subjects
      were divided into two groups and were shown three enhancement levels. Original
      and medium enhancements were shown to both groups. High enhancement was shown to
      group 1, and low enhancement was shown to group 2. For search, subjects pointed
      to an object that matched a search target displayed at the top left of the
      screen. An "integrated search performance" measure (area under the curve of
      cumulative correct response rate over search time) quantified performance. For
      preference, subjects indicated the preferred side when viewing the same image
      with different enhancement levels on side-by-side high-definition televisions.
      RESULTS: Contour enhancement did not improve performance in the visual search
      task. Group 1 subjects significantly (p < 0.001) rejected the High enhancement,
      and showed no preference for medium enhancement over the original images. Group 2
      subjects significantly preferred (p < 0.001) both the medium and the low
      enhancement levels over original. Contrast sensitivity was correlated with both
      preference and performance; subjects with worse contrast sensitivity performed
      worse in the search task (rho = 0.77, p < 0.001) and preferred more enhancement
      (rho = -0.47, p = 0.02). No correlation between visual search performance and
      enhancement preference was found. However, a small group of subjects (n = 6) in a
      narrow range of mid-contrast sensitivity performed better with the enhancement,
      and most (n = 5) also preferred the enhancement. CONCLUSIONS: Preferences for
      image enhancement can be dissociated from search performance in people with
      vision impairment. Further investigations are needed to study the relationships
      between preference and performance for a narrow range of mid-contrast sensitivity
      where a beneficial effect of enhancement may exist.

PMID- 22863794
TI  - Outcomes in the management of appendicitis and cholecystitis in the setting of a
      new acute care surgery service model: impact on timing and cost.
AB  - BACKGROUND: The acute care surgery model is a novel notion in the provision of
      emergency general surgery. To date, several studies have analyzed the effects on
      patient health outcomes and timeliness of care for nontrauma patients within the
      scope of acute general surgery and emergencies, but none have assessed the cost
      benefits of this model. STUDY DESIGN: A retrospective analysis of patients
      undergoing appendectomy or cholecystectomy in the setting of acute abdomen was
      performed to compare data from 2 cohorts, the traditional model from July 2009 to
      June 2010 and the acute care surgery model from July 2010 to June 2011.
      Categorical variables and comparison means were examined using chi-square and
      independent 2-tailed sample t-tests. RESULTS: One hundred and seventy-five
      patients underwent appendectomy and 113 underwent cholecystectomy. The
      traditional model team staffed 82 appendectomies and 51 cholecystectomies, and
      the acute care surgery team staffed 93 and 62, respectively. In the appendectomy
      group, there was a statistically significant mean reduction of time to surgical
      evaluation (2.19 hours; p < 0.001) and time to the operating room (5.38 hours, p
      = 0.006), there were 7 fewer patients with complications (p = 0.06) and a reduced
      length of stay (1 day, p = 0.002) for the acute care surgery cohort. Similar
      statistically significant differences were observed in the cholecystectomy group
      in the acute care surgery cohort: surgical evaluation difference = 5.84 hours (p
      = 0.03), time to operating room difference = 25.37 hours (p = 0.002), 8 fewer
      patients with complications (p = 0.01), and length of stay difference was 2 days
      (p = 0.03) compared with the traditional model cohort. CONCLUSIONS: The newly
      implemented acute care surgery model in our institution accomplished earlier
      treatment and shorter length of stay for the 2 most common causes of acute
      abdomen in our setting. Overall, the new model translated to better outcomes for
      patients and savings per case for the hospital.

PMID- 22863795
TI  - Age-stratified results from 20,095 aortoiliac aneurysm repairs: should we
      approach octogenarians and nonagenarians differently?
AB  - BACKGROUND: In the endovascular era, elderly patients are offered repair of their
      aortoiliac aneurysms (AAA) more frequently than in the past. Our objective is to
      compare age groups and draw inferences for AAA repair outcomes. STUDY DESIGN: We
      identified 20,095 patients who underwent AAA repair between 2005 and 2010 using
      the American College of Surgeons NSQIP national database. Preoperative
      characteristics and outcomes were compared among age groups (group A: 0 to 64
      years; B: 65 to 79 years; C: 80 to 89 years; and D: 90 years and older). RESULTS:
      The age distribution of the cohort was A: 17.1%, B: 57.2%, C: 24%, and D: 1.7%.
      Nonagenarians presented significantly more often as emergencies in comparison
      with groups A to C (A: 13.8%, B: 10.8%, C: 12.9%, D: 22.1%; p < 0.001).
      Endovascular aneurysm repair was performed more frequently in older patients (A:
      55.2%, B: 63.7%, C: 74.6%, D: 77.9%; p < 0.001). Risk of any complication was
      significantly different among groups, becoming more prevalent with advanced age
      (A: 22.8%, B: 23.4%, C: 24.7%, D: 27.8%; p = 0.041). Nonsurgical complications
      (A: 14.7%, B: 16.4%, C: 18%, D: 19.8%; p < 0.001) and cardiovascular
      complications (A: 3.9%, B: 4.5%, C: 5.5%, D: 5.2%; p = 0.003) were also higher
      with advanced age. Overall mortality was 3.1%, 4.9%,7.2%, and 13.2% for groups A
      to D, respectively (p < 0.001). Mortality after elective AAA repair was
      significantly higher for open surgery compared with endovascular aneurysm repair
      in all age groups (open surgery vs endovascular aneurysm repair, A:1.9% vs 0.5%;
      p = 0.001; B: 3.9% vs 1.2%; p < 0.001; C: 7.4% vs 2%; p < 0.001; D: 18.8% vs
      3.8%; p = 0.004). After adjusting for confounders in the entire cohort, advanced
      age persisted as an independent factor for postoperative mortality with a higher
      risk of death of 1.8 (95% CI, 1.3-2.5), 2.7 (95% CI, 1.9-3.8), and 3.3 (95% CI,
      1.8-6.1) times for groups B, C, and D, respectively (group A reference).
      CONCLUSIONS: Advanced age is independently associated with higher risk of death
      after AAA repair and indication for surgery should be adjusted for different age
      groups accordingly. Endovascular aneurysm repair should be preferred for
      octogenarians and nonagenarians with indication to undergo repair of their AAA.

PMID- 22863796
TI  - The fatal disease of Emperor Galerius.

PMID- 22863797
TI  - Surgical interest and surgical match for third-year students: results of a
      prospective multivariate longitudinal cohort study.
AB  - BACKGROUND: Numerous factors have been linked to surgical career choice,
      including the quality of third-year surgical clerkship. The vast majority of
      studies also selectively evaluate one or only a few variables that link to
      surgical career choice, so relative impact cannot be assessed. This study
      simultaneously evaluates the majority of variables linked to surgical career
      choice in previous research so that the relative contributions of each of these
      variables with respect to surgical career choice can be determined. STUDY DESIGN:
      Surveys before, during, and after the third-year surgical clerkship included
      student demographics, background, and values (eg, importance of money,
      controllable lifestyle), and student reactions to the third-year surgical
      clerkship. The dependent variables in this study included interest in surgery at
      the beginning and end of the clerkship and matching into a surgical residency.
      RESULTS: Both univariate and multivariate analyses generally supported findings
      in the literature, but the strengths of these associations reported previously
      might not have been accurate. In this study, the surgical resident match odds
      ratio for students starting the clerkship already knowing they wanted to be a
      surgeon was 22.46; the next highest associations were 4.65 and 3.37, which
      corresponded to earlier exposure to a surgical specialty and earlier exposure to
      general surgery, respectively. Differences in career choice for general surgeons
      and surgical specialists were also explored. CONCLUSIONS: Although the experience
      of the clerkship is related to career choice, the largest impact of the clerkship
      is for those already interested in a surgical career. Interest in a surgical
      career largely develops before the third-year clerkship. Implications of the
      results for recruiting greater numbers of students into surgical careers are
      discussed.

PMID- 22863798
TI  - Design, synthesis and anti-inflammatory activity of structurally simple
      anthranilic acid congeners devoid of ulcerogenic side effects.
AB  - Simple, three classes of new anthranilic acid derivatives were aimed at,
      synthesized and tested for their toxicity, anti-inflammatory, analgesic,
      antipyretic activity. Also, their potential protective role against ulcerative
      colitis in rats was performed. Furthermore, their effect on liver and kidney
      functions was detected through measurement of the serum level of alanine
      transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and other
      parameters. Compounds 4, 5, 6b, 6c, 7c and 7e showed significant anti
      inflammatory activity. From those 6b and 7e best improved the inflammatory
      indices even producing better reduction in the intensity of lesion score, ulcer
      area and wet weight/length ratio and showed good analgesic activity. Fortunately,
      none of the tested compounds showed any hepatotoxicity or nephrotoxicity. None of
      the tested compounds showed any antipyretic activity. Conclusively, presence of a
      phenyl ring in the substituent added is a must, since any alteration in its
      nature led to decrease in activity. Also, the presence of an extra halogen in
      addition to the one already embedded in the main structure was detrimental to
      activity.

PMID- 22863799
TI  - Bioproduction of Cinchona alkaloids by the endophytic fungus Diaporthe sp.
      associated with Cinchona ledgeriana.
AB  - We report that an endophytic filamentous fungus species of the genus Diaporthe
      isolated from Cinchona ledgeriana (Rubiaceae) produces Cinchona alkaloids
      (quinine, quinidine, cinchonidine, and cinchonine) upon cultivation in a
      synthetic liquid medium. This study provides evidence that Cinchona alkaloids are
      produced not only in Cinchona plant cells, but also in the endophytic microbe
      cells, and will help to elucidate the relationship between endophytic microbes
      and their host plants.

PMID- 22863800
TI  - Mucoadhesive tablets for controlled release of acyclovir.
AB  - Mucoadhesive chitosan (CS) and/or hydroxypropyl-methylcellulose (HPMC) tablets
      for gastric drug delivery of acyclovir (ACV) have been developed in order to
      improve the ACV oral bioavailability. Swelling, bioadhesive and dissolution
      studies were carried out in two acidic media (pH 1.5 and 4) in order to determine
      the tablets behaviour in both fed and fasted states. All the designed tablets
      showed good mucoadhesive properties on gastric mucosa due to the presence of CS
      and/or HPMC. In vitro dissolution of ACV from tablets was influenced by the
      swelling behaviour of each polymer. All data release of the studied tablets
      fitted to Hopfenberg model, which describes drug release from tablets displaying
      heterogeneous erosion. HPMC and CS/HPMC tablets revealed a sustained release for
      24 h, but a complete dissolution of the tablets was not produced at this time. On
      the contrary, tablets which contained only CS as polymer were able to release the
      total amount of ACV for 4 h, due to the CS imbibition and erosion processes in pH
      1.5 medium. These results allowed us to conclude that CS is the excipient to be
      chosen to obtain gastroretentive formulations, due to its demonstrated gastric
      compatibility.

PMID- 22863801
TI  - Screening for latent tuberculosis in anti-TNF-alpha candidate patients in a high
      tuberculosis incidence setting.
AB  - BACKGROUND: Screening for latent tuberculosis infection (LTBI) using a protocol
      comprising chest X-ray and tuberculin skin test (TST) interpreted with medical
      history, Sc1, reduces LTBI reactivation on treatment with anti-tumour necrosis
      factor-alpha (anti-TNF-alpha). In the district of Seine-Saint-Denis, France,
      where tuberculosis (TB) incidence ranges from 30 to >100/100 000 person-years,
      however, Sc1 might be insensitive as a screening tool. We adopted another
      protocol, Sc2, comprising Sc1 plus two additional tests: the QuantiFERON((r))-TB
      Gold In-Tube (QFT-GIT) and chest computed tomography (CT). METHODS: We screened
      123 consecutive patients with inflammatory rheumatic diseases (IRDs), candidates
      for anti-TNF-alpha treatment, and evaluated the impact of Sc2 vs. Sc1 on the
      prescription of prophylactic anti-tuberculosis treatment. RESULTS: Sc2 led to a
      diagnosis of LTBI in 69 patients vs. 59 when using Sc1: eight were QFT-GIT
      positive. Diagnosis was based on CT findings in two patients. QFT-GIT had higher
      diagnostic accuracy than TST, but no single diagnostic test could detect all
      patients at high risk for LTBI reactivation (respectively 30.2% and 37.5% of
      patients positive with only TST or QFT-GIT). CT detected TB sequelae in 3/46
      rheumatoid arthritis patients who were negative to all tests. CONCLUSIONS:
      Testing with both TST and QFT-GIT seems the safest strategy for detecting LTBI in
      patients with IRD from populations with high incidence of TB. Systematic
      screening with CT warrants further evaluation.

PMID- 22863802
TI  - Cytosolic clearance of replication-deficient mutants reveals Francisella
      tularensis interactions with the autophagic pathway.
AB  - Cytosolic bacterial pathogens must evade intracellular innate immune recognition
      and clearance systems such as autophagy to ensure their survival and
      proliferation. The intracellular cycle of the bacterium Francisella tularensis is
      characterized by rapid phagosomal escape followed by extensive proliferation in
      the macrophage cytoplasm. Cytosolic replication, but not phagosomal escape,
      requires the locus FTT0369c, which encodes the dipA gene (deficient in
      intracellular replication A). Here, we show that a replication-deficient, ?dipA
      mutant of the prototypical SchuS4 strain is eventually captured from the cytosol
      of murine and human macrophages into double-membrane vacuoles displaying the late
      endosomal marker, LAMP1, and the autophagy-associated protein, LC3, coinciding
      with a reduction in viable intracellular bacteria. Capture of SchuS4DeltadipA was
      not dipA-specific as other replication-deficient bacteria, such as
      chloramphenicol-treated SchuS4 and a purine auxotroph mutant SchuS4DeltapurMCD,
      were similarly targeted to autophagic vacuoles. Vacuoles containing replication
      deficient bacteria were labeled with ubiquitin and the autophagy receptors
      SQSTM1/p62 and NBR1, and their formation was decreased in macrophages from either
      ATG5-, LC3B- or SQSTM1-deficient mice, indicating recognition by the ubiquitin
      SQSTM1-LC3 pathway. While a fraction of both the wild-type and the replication
      impaired strains were ubiquitinated and recruited SQSTM1, only the replication
      defective strains progressed to autophagic capture, suggesting that wild-type
      Francisella interferes with the autophagic cascade. Survival of replication
      deficient strains was not restored in autophagy-deficient macrophages, as these
      bacteria died in the cytosol prior to autophagic capture. Collectively, our
      results demonstrate that replication-impaired strains of Francisella are cleared
      by autophagy, while replication-competent bacteria seem to interfere with
      autophagic recognition, therefore ensuring survival and proliferation.

PMID- 22863803
TI  - The structure of myristoylated Mason-Pfizer monkey virus matrix protein and the
      role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding.
AB  - We determined the solution structure of myristoylated Mason-Pfizer monkey virus
      matrix protein by NMR spectroscopy. The myristoyl group is buried inside the
      protein and causes a slight reorientation of the helices. This reorientation
      leads to the creation of a binding site for phosphatidylinositols. The
      interaction between the matrix protein and phosphatidylinositols carrying C(8)
      fatty acid chains was monitored by observation of concentration-dependent
      chemical shift changes of the affected amino acid residues, a saturation transfer
      difference experiment and changes in (31)P chemical shifts. No differences in the
      binding mode or affinity were observed with differently phosphorylated
      phosphatidylinositols. The structure of the matrix protein-phosphatidylinositol
      (4,5)-bisphosphate [PI(4,5)P(2)] complex was then calculated with HADDOCK
      software based on the intermolecular nuclear Overhauser enhancement contacts
      between the ligand and the matrix protein obtained from a (13)C-filtered/(13)C
      edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P(2)
      binding was not strong enough for triggering of the myristoyl-switch. The
      structural changes of the myristoylated matrix protein were also found to result
      in a drop in the oligomerization capacity of the protein.

PMID- 22863805
TI  - Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by
      inhibiting SREBP to decrease lipid biosynthesis.
AB  - gp78 is a membrane-anchored ubiquitin ligase mediating the degradation of HMG-CoA
      reductase (HMGCR) and Insig-1. As a rate-limiting enzyme in cholesterol
      biosynthesis, HMGCR undergoes rapid sterol-promoted degradation. In contrast,
      destruction of Insig-1 releases its inhibition on SREBP and stimulates the
      expression of lipogenic genes. Thus, gp78 has opposite effects on lipid
      biosynthesis. We here generated liver-specific gp78 knockout (L-gp78(-/-)) mice
      and showed that although the degradation of HMGCR was blunted, SREBP was
      suppressed due to the elevation of Insig-1/-2, and therefore the lipid
      biosynthesis was decreased. The L-gp78(-/-) mice were protected from diet-/age
      induced obesity and glucose intolerance. The livers of L-gp78(-/-) mice produced
      more FGF21, which activated thermogenesis in brown adipocytes and enhanced energy
      expenditure. Together, the major function of gp78 in liver is regulating lipid
      biosynthesis through SREBP pathway. Ablation of gp78 decreases the lipid levels
      and increases FGF21, and is beneficial to patients with metabolic diseases.

PMID- 22863806
TI  - Exposure analysis of accidental release of mercury from compact fluorescent lamps
      (CFLs).
AB  - Mercury release after breakage of compact fluorescent lamps (CFLs) has recently
      become an issue of public health concern, especially in the case of early life
      infants. Preliminary, screening type calculations have indicated that there is
      potential for increased intake of mercury vapor by inhalation after breakage of a
      CFL. Several experimental and computational studies have shown that, when
      modeling the breakage of a CFL, the room space must be segregated into different
      zones, according to the potential of mercury vapor to accumulate in them after
      accidental release. In this study, a detailed two-zone model that captures the
      physicochemical processes that govern mercury vapor formation and dispersion in
      the indoor environment was developed. The mercury fate model was coupled to a
      population exposure model that accounts for age and gender-related differences in
      time-activity patterns, as well as country differences in body weight and age
      distribution. The parameters above are used to determine the intake through
      inhalation (gas phase and particles) and non-dietary ingestion (settled dust) for
      each age, gender group and ethnicity. Results showed that the critical period for
      intake covers the first 4h after the CFL breaks and that room air temperature
      significantly affects the intake rate. Indoor air concentration of mercury vapor
      may exceed toxicological thresholds of concern such as the acute Reference
      Exposure Limit (REL) for mercury vapor set by the Environmental Protection Agency
      of California. Ingestion intake through hand-to-mouth behavior is significant for
      infants and toddlers, counting for about 20% of the overall intake. Simple risk
      reduction measures including increased indoor ventilation followed by careful
      clean-up of the accident site, may limit dramatically the estimated health risk.

PMID- 22863804
TI  - Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma
      activation to decrease diet-induced obesity.
AB  - De novo lipogenesis in adipocytes, especially with high fat feeding, is poorly
      understood. We demonstrate that an adipocyte lipogenic pathway encompassing fatty
      acid synthase (FAS) and PexRAP (peroxisomal reductase activating PPARgamma)
      modulates endogenous PPARgamma activation and adiposity. Mice lacking FAS in
      adult adipose tissue manifested increased energy expenditure, increased brown fat
      like adipocytes in subcutaneous adipose tissue, and resistance to diet-induced
      obesity. FAS knockdown in embryonic fibroblasts decreased PPARgamma
      transcriptional activity and adipogenesis. FAS-dependent alkyl ether
      phosphatidylcholine species were associated with PPARgamma and treatment of 3T3
      L1 cells with one such ether lipid increased PPARgamma transcriptional activity.
      PexRAP, a protein required for alkyl ether lipid synthesis, was associated with
      peroxisomes and induced during adipogenesis. PexRAP knockdown in cells decreased
      PPARgamma transcriptional activity and adipogenesis. PexRAP knockdown in mice
      decreased expression of PPARgamma-dependent genes and reduced diet-induced
      adiposity. These findings suggest that inhibiting PexRAP or related lipogenic
      enzymes could treat obesity and diabetes.

PMID- 22863808
TI  - Circulating metals and persistent organic pollutant concentrations in Canadian
      and non-Canadian born primiparous women from five Canadian centres: results of a
      pilot biomonitoring study.
AB  - The developing foetus is thought to be at increased risk from exposure to
      environmental contaminants; however, developmental exposure data is notably
      lacking for many contaminants. Moreover, potential regional differences or effect
      of place of birth on residue levels measured in pregnant women is also unknown.
      Therefore, as part of a multinational biomonitoring study, 125 primiparous
      pregnant Canadian women were recruited from five Canadian centres (Vancouver,
      Calgary, Hamilton, Ottawa, and Halifax). Metals in whole blood and persistent
      organic pollutants (POPs) in plasma were measured by inductively coupled plasma
      mass spectrometry (ICPMS) and gas chromatography-mass spectrometry (GCMS),
      respectively. Of the 125 women recruited to this study, complete data sets were
      available for 123 of which 103 were Canadian born. Data were analysed by analysis
      of covariance and linear mixed models using age and body mass index as
      covariates. The metals cadmium (Cd), cobalt (Co), lead (Pb), nickel (Ni),
      selenium (Se), and total mercury (Hg) were detected in more than 93% of the
      samples tested. beta-Hexachlorohexane (beta-HCH), oxychlordane, trans-nonachlor,
      1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), polybrominated diphenyl
      ether (PBDE) congeners (PBDE-153, PBDE-47), polychlorinated biphenyl (PCB)
      congeners (PCB-138, -153, and -180), and the dioxin-like PCB congener PCB-118
      were quantified in greater than 70% of the samples tested. Significant
      differences in the concentrations of Cd, Ni, PCB-153, and p,p'-DDE were found
      between the centres studied. Furthermore, foreign-born pregnant women had
      significantly higher concentrations of Cd, beta-HCH, PBDE-47, PCB-138, -153, 
      180, and p,p'-DDE compared to Canadian born pregnant women. Taken together, the
      data suggest that there are potential regional differences in contaminant body
      burden and place of birth may also contribute to differences in maternal residue
      concentrations.

PMID- 22863807
TI  - Incorporating exposure information into the toxicological prioritization index
      decision support framework.
AB  - The Toxicological Prioritization Index (ToxPi) decision support framework was
      previously developed to facilitate incorporation of diverse data to prioritize
      chemicals based on potential hazard. This ToxPi index was demonstrated by
      considering results of bioprofiling related to potential for endocrine
      disruption. However, exposure information is required along with hazard
      information to prioritize chemicals for further testing. The goal of this
      analysis is to demonstrate the utility of the ToxPi framework for incorporating
      exposure information to rank chemicals and improve understanding of key exposure
      surrogates. The ToxPi tool was applied to common exposure surrogates (i.e., fate
      parameters, manufacturing volume, and occurrence measurements) and the
      relationship between resulting rankings and higher-tiered exposure estimates was
      investigated. As information more directly relevant to human exposure potential
      is incorporated, relative rank of chemicals changes. Binned ToxPi results are
      shown to be consistent with chemical priorities based on crude measures of
      population-level exposure for a limited set of chemicals. However, these bins are
      not predictive of higher tiered estimates of exposure such as those developed for
      pesticide registration. Although rankings based on exposure surrogates are used
      in a variety of contexts, analysis of the relevance of these tools is
      challenging. The ToxPi framework can be used to gain insight into the factors
      driving these rankings and aid identification of key exposure metrics. Additional
      exposure data is required to build confidence in exposure-based chemical
      prioritization.

PMID- 22863809
TI  - Sorption of dissolved organic matter in salt-affected soils: effect of salinity,
      sodicity and texture.
AB  - Loss of dissolved organic matter (DOM) from soils can have negative effects on
      soil fertility and water quality. It is known that sodicity increases DOM
      solubility, but the interactive effect of sodicity and salinity on DOM sorption
      and how this is affected by soil texture is not clear. We investigated the effect
      of salinity and sodicity on DOM sorption in soils with different clay contents.
      Four salt solutions with different EC and SAR were prepared using combinations of
      1M NaCl and 1M CaCl(2) stock solutions. The soils differing in texture (4, 13, 24
      and 40% clay, termed S-4, S-13, S-24 and S-40) were repeatedly leached with these
      solutions until the desired combination of EC and SAR (EC(1:5) 1 and 5dSm(-1) in
      combination with SAR <3 or >20) was reached. The sorption of DOC (derived from
      mature wheat straw) was more strongly affected by SAR than by EC. High SAR (>20)
      at EC1 significantly decreased sorption in all soils. However, at EC5, high SAR
      did not significantly reduce DOC sorption most likely because of the high
      electrolyte concentration of the soil solution. DOC sorption was greatest in S-24
      (which had the highest CEC) at all concentrations of DOC added whereas DOC
      sorption did not differ greatly between S-40 and S-4 or S-13 (which had higher
      concentrations of Fe/Al than S-40). DOC sorption in salt-affected soil is more
      strongly controlled by CEC and Fe/Al concentration than by clay concentration per
      se except in sodic soils where DOC sorption is low due to the high sodium
      saturation of the exchange complex.

PMID- 22863810
TI  - New insight into photo-bromination processes in saline surface waters: the case
      of salicylic acid.
AB  - It was shown, through a combination of field and laboratory observations, that
      salicylic acid can undergo photo-bromination reactions in sunlit saline surface
      waters. Laboratory-scale experiments revealed that the photochemical yields of 5
      bromosalicylic acid and 3,5-dibromosalicylic acid from salicylic acid were always
      low (in the 4% range at most). However, this might be of concern since these
      compounds are potential inhibitors of the 20alpha-hydroxysteroid dehydrogenase
      enzyme, with potential implications in endocrine disruption processes. At least
      two mechanisms were involved simultaneously to account for the photo-generation
      of brominated substances. The first one might involve the formation of reactive
      brominated radical species (Br, Br(2)(-)) through hydroxyl radical mediated
      oxidation of bromide ions. These ions reacted more selectively than hydroxyl
      radicals with electron-rich organic pollutants such as salicylic acid. The second
      one might involve the formation of hypobromous acid, through a two electron
      oxidation of bromine ions by peroxynitrite. This reaction was catalyzed by
      nitrite, since these ions play a crucial role in the formation of nitric oxide
      upon photolysis. This nitric oxide further reacts with superoxide radical anions
      to yield peroxynitrite and by ammonium through the formation of N-bromoamines,
      probably due to the ability of N-bromoamines to promote the aromatic bromination
      of phenolic compounds. Field measurements revealed the presence of salicylic acid
      together with 5-bromosalicylic and 3,5-dibromosalicylic acid in a brackish
      coastal lagoon, thus confirming the environmental significance of the proposed
      photochemically induced bromination pathways.

PMID- 22863811
TI  - Seasonal variations in surface water chemistry at disturbed and pristine peatland
      sites in the Flow Country of northern Scotland.
AB  - Weekly monitoring of surface water chemistry took place over a one-year period in
      a small boggy sub-catchment of the River Thurso, northern Scotland. Monitoring
      started 6 months after the felling to waste of plantation conifers. The chemistry
      of ground surface waters was monitored at four bog sites situated in former
      forestry plots as well as one control site situated in an intact bog. The
      chemistry of the receiving stream (Sleach Water) was monitored at seven points
      along a 2 km stretch. Dissolved organic carbon and metals were very significantly
      affected by seasonal factors. On land, seasonal variations accounted for between
      35% (Al) and 80% (Fe) of the total variance in the data at the intact bog site,
      with similar seasonal effects observed at the impacted sites. The amplitude of
      the seasonal signal was generally much higher at the impacted sites than at the
      control site. Except for dissolved Al and Mn, the chemical composition of the
      stream was only marginally influenced by surface runoff from the felled
      plantation despite evidence of intense seasonal mobilisation of e.g. DOC, K or Fe
      at or near the ground surface within the felled plots. This was attributed to the
      presence of a buffer zone between the plantation and the stream. On the other
      hand, surface inputs from former forestry plots caused measurable increases in
      stream water [Al] and [Mn]. The likely sources of Al and Mn were the disturbance
      of the mineral soil that had taken place some 20 years previously as a result of
      forestry ground preparation and the leaching from the recently felled conifer
      material, respectively. Such inputs occurred in late autumn or winter for Al and
      in summer for Mn, thus intensifying their natural seasonal patterns in this peat
      draining stream.

PMID- 22863813
TI  - Direct-write non-linear photolithography for semiconductor nanowire
      characterization.
AB  - A practical bottleneck prohibiting the rapid, confident and damage-free
      electrical contacting of vapour-liquid-solid grown nanowires arises from the
      random spatial distribution and variation in quality of the nanowires, and the
      contact dimensions required. Established techniques such as electron-beam
      lithography or focused ion-beam deposition have challenges in scaling, damage or
      complexity that can make a large statistical sample difficult. We present a
      direct laser-writing technique to allow rapid electrical contacting of nanowires
      on a large variety of substrates.

PMID- 22863812
TI  - The yield of different pleural fluid volumes for Mycobacterium tuberculosis
      culture.
AB  - We prospectively compared the culture yields of two pleural fluid volumes (5 and
      100 ml) inoculated in liquid culture medium in 77 patients of whom 58 (75.3%)
      were diagnosed with pleural tuberculosis. The overall fluid culture yield was
      high (60.3% of cases with pleural tuberculosis). The larger volume had a faster
      time to positivity (329 vs 376 h, p=0.055) but its yield was not significantly
      higher (53.5% vs 50%; p=0.75). HIV-positive patients were more likely to have
      positive cultures (78.9% vs 51.5%; p=0.002).

PMID- 22863814
TI  - G protein-coupled receptor FPR1 as a pharmacologic target in inflammation and
      human glioblastoma.
AB  - Formylpeptide receptor1 (FPR1) is a G protein-coupled receptor (GPCR) originally
      identified in phagocytic leucocytes and mediates cell chemotaxis and activation
      in response to bacterial formylated chemotactic peptides. However, FPR1 also
      participates in a signal relay which regulates the infiltration of phagocytes, in
      particular neutrophils, to inflammatory sites in response to tissue-derived
      chemoattractant ligands. In addition to participating in innate immune responses,
      recently, FPR1 has been shown to be expressed by highly malignant glioblastoma
      (GBM) cells. Upon activation by an endogenous agonist Annexin 1 (Anx A1) released
      by necrotic glioma cells, FPR1 transactivates the receptor for epithelial growth
      factor (EGFR) and consequently to promote glioma cell chemotaxis, invasion,
      growth and production of angiogenic factors. The observations demonstrate that
      FPR1, as a multifunctional GPCR with pattern recognition properties, is not only
      involved in innate immune responses but also in the progression of GBM. Thus,
      FPR1 is an immunopharmacologic target for development of novel therapies.

PMID- 22863815
TI  - A Janus cobalt-based catalytic material for electro-splitting of water.
AB  - The future of energy supply depends on innovative breakthroughs regarding the
      design of cheap, sustainable and efficient systems for the conversion and storage
      of renewable energy sources. The production of hydrogen through water splitting
      seems a promising and appealing solution. We found that a robust nanoparticulate
      electrocatalytic material, H(2)-CoCat, can be electrochemically prepared from
      cobalt salts in a phosphate buffer. This material consists of metallic cobalt
      coated with a cobalt-oxo/hydroxo-phosphate layer in contact with the electrolyte
      and mediates H(2) evolution from neutral aqueous buffer at modest overpotentials.
      Remarkably, it can be converted on anodic equilibration into the previously
      described amorphous cobalt oxide film (O(2)-CoCat or CoPi) catalysing O(2)
      evolution. The switch between the two catalytic forms is fully reversible and
      corresponds to a local interconversion between two morphologies and compositions
      at the surface of the electrode. After deposition, the noble-metal-free coating
      thus functions as a robust, bifunctional and switchable catalyst.

PMID- 22863816
TI  - In vivo confocal microscopy of the cornea in Morquio syndrome.

PMID- 22863817
TI  - Management of skin retraction associated with Boston type II keratoprosthesis.

PMID- 22863818
TI  - Reliability of a question inventory for structured history taking in children
      with cerebral visual impairment.

PMID- 22863819
TI  - Comment on 'Corneal hysteresis in patients with dry eye'.

PMID- 22863820
TI  - Long-term results of 360A degrees  scleral buckling and vitrectomy with silicone
      oil tamponade for management of gunshot-perforating ocular injury.
AB  - PURPOSE: This is a retrospective consecutive study to assess the long-term
      results of combined scleral buckling and pars plana vitrectomy (PPV) with
      silicone oil for the management of perforating ocular injury caused by gunshots.
      METHODS: Data were gathered from medical records of patients who underwent
      scleral buckling and PPV with silicone oil 2 weeks after primary repair
      elsewhere, in Magrabi eye center (Tanta, Egypt), from June 2005 to May 2010.
      RESULTS: The evaluated group consisted of 49 cases, out of which 26 cases
      presented with gunshot injury. Twenty-two were male (84.62%) and four were female
      (15.38%), with a mean age of 27.19+12.7 years. The follow-up ranged from 12 to 72
      months, with a mean period of 32.04+8.9 months. The t-test was used to determine
      the visual outcome and main prognostic factors. Visual acuity improved in 22 of
      26 eyes (76.92%), was unchanged in 4 eyes (15.38%), and worsened in 2 eyes
      (6.69%). Ten eyes (38.46%) achieved visual acuity between (20/40) and (20/100),
      and eight eyes (30.76%) had visual acuity between (20/200) and (20/400). The 18
      eyes (69.23%) with visual acuity better than counting fingers (CF) had an
      attached retina with no signs of active proliferation after removal of the
      silicone oil. CONCLUSION: POI due to gunshot is usually a terminal event for the
      eye. Eyes with perforating injury can be saved and may attain useful vision after
      performance of combined scleral buckling and PPV with silicone oil tamponade. The
      final visual outcome depends on the macular or the optic nerve involvement and
      the final retinal stability, and phthisis bulbi can also be prevented.

PMID- 22863821
TI  - Decompensated septic shock in the setting of megace-induced severe adrenal
      suppression in an otherwise healthy pediatric patient: a case report.
AB  - A previously healthy 4-year-old boy presented to the emergency department at the
      Children's Hospital of Alabama with pneumonia caused by Pneumococcus infection
      and rapid progression to circulatory collapse. He was described as previously
      healthy except for being a "picky eater" and has been taking Megace (megestrol
      acetate) as an appetite stimulant for the past 2 years. We believe that the
      severity of his presentation was due in part to severe adrenal suppression from
      long-term Megace use. We were able to successfully resuscitate him with the
      addition of stress dose hydrocortisone, and he went on to have a complete
      recovery without any permanent disability. Previous literature has reported the
      adverse effect of Megace in suppressing adrenal function in patients with cancer
      and acquired immunodeficiency syndrome. This is the first report of this adverse
      effect in an otherwise healthy child. As the use of Megace becomes more
      widespread as an appetite stimulant in children, we hope to raise awareness of
      this important, potentially life-threatening adverse effect among physicians.

PMID- 22863822
TI  - Arthritis caused by group B Streptococcus: a case report.
AB  - Streptococcus agalactiae is not only a well-known cause of severe infections in
      the first 3 months of life but also an unusual organism to be isolated in case of
      septic arthritis, especially in children. We report a case of a monoarticular
      arthritis in a 6-month-old girl.

PMID- 22863823
TI  - Adverse effects of steroid therapy in children with pharyngitis with unsuspected
      malignancy.
AB  - Pharyngitis is a common clinical complaint for children and accounts for 3.1% of
      all visits to selected ambulatory care settings. Most children with pharyngitis
      have benign, self-limited disease with infrequent complications such as
      peritonsillar abscess, mastoiditis, or lymphadenitis. Recent studies have touted
      the benefits of steroids in the treatment of children with pharyngitis for pain
      control. These studies do not address the potential life-threatening complication
      of steroids in patients with pharyngitis or lymphadenopathy in the setting of
      undiagnosed acute lymphocytic leukemia (ALL) or lymphoma. We report 4 cases of
      children treated with steroids for pharyngitis or adenitis that subsequently were
      diagnosed with ALL or lymphoma. If steroids are to be used in children with
      pharyngitis or adenitis, the following recommendations should be strongly
      considered: Careful history and physical examination should be obtained. Presence
      of hepatosplenomegaly or lymphadenopathy outside the cervical region should raise
      suspicions regarding an underlying malignancy. Normal results of complete blood
      cell count in the setting of clear cut pharyngitis with exudates and a lack of
      significant adenopathy essentially rules out the diagnosis of ALL. Because
      traditional analgesics are available, which do not affect the curability of ALL
      or lymphoma, the routine use of steroids in pharyngitis in children should be
      considered only in rare circumstances.

PMID- 22863824
TI  - Tissue glue and iatrogenic eyelid gluing in children.
AB  - Tissue glues are commonly used in emergency departments to treat straight-edged
      lacerations and are advocated for use on the face or head. Although application
      is relatively quick and easy, this can potentially lead to inadvertent eyelid
      involvement, with potential medicolegal implications. We present 2 cases of such
      eyelid gluing with tissue glue after it was used on children for closure of
      supraorbital lacerations.

PMID- 22863825
TI  - Elemental mercury poisoning presenting as hypertension in a young child.
AB  - Mercury intoxication is an uncommon cause of hypertension in children and can
      mimic several other diseases, such as pheochromocytoma and vasculitis. Mercury
      intoxication can present as a diagnostic challenge because levels of
      catecholamines may be elevated, suggesting that the etiology is a catecholamine
      secreting tumor. Once acrodynia is identified as a primary symptom, a 24-hour
      urine mercury level can confirm the diagnosis. Inclusion of mercury intoxication
      in the differential diagnosis early on can help avoid unnecessary and invasive
      diagnostic tests and therapeutic interventions. We discuss a case of mercury
      intoxication in a 3-year-old girl presenting with hypertension and acrodynia,
      without a known history of exposure. Chelation therapy successfully treated our
      patient's mercury intoxication. However, it was also necessary to concurrently
      treat her hypertension and the pain associated with her acrodynia. Because there
      were no known risk factors for mercury poisoning in this case, and because ritual
      use of mercury is common in much of the United States, we recommend high clinical
      suspicion and subsequent testing in all cases of acrodynia.

PMID- 22863826
TI  - Dead sea water intoxication.
AB  - Near drowning in the Dead Sea is associated with both respiratory manifestations
      and severe electrolyte abnormalities. It is often difficult to distinguish
      between the contributions of sea water aspiration or ingestion to clinical
      manifestations. We present a unique case of accidental ingestion of a large
      amount of Dead Sea water through a gastrostomy tube in which a patient with
      familial dysautonomia presented with severe electrolyte disturbances. Forced
      diuresis with large amounts of intravenous fluids resulted in clinical and
      biochemical improvement. Full recovery was achieved after 2 days of treatment.

PMID- 22863827
TI  - Recognizing serotonin toxicity in the pediatric emergency department.
AB  - The use of selective serotonin reuptake inhibitors and serotonin-norepinephrine
      reuptake inhibitors in treating depression, mood disorders, and behavioral
      disorders has escalated dramatically in the last 20 years, resulting in increased
      risk and clinical presentation of serotonin toxicity. Health care providers must
      also be aware of other medications and substances with proserotonergic activity
      that can cause serotonin toxicity when used in combination with these
      medications. There are many adverse effects of selective serotonin reuptake
      inhibitors and serotonin-norepinephrine reuptake inhibitors, although their
      toxicity profile compared to older antidepressants seems to be safer. Serotonin
      syndrome is described as a clinical triad of mental status changes, autonomic
      hyperactivity, and neuromuscular abnormalities. It encompasses a spectrum of
      clinical findings ranging from a few nonspecific symptoms to significant clinical
      toxicity that can result in death. The objectives of this article are to review
      specific serotonergic medications including their adverse effects and toxicity in
      overdose, to describe other medications/substances that have proserotonergic
      effects, which could result in serotonin excess in combination with traditional
      serotonergic agents, and to define the criteria for serotonin syndrome/toxicity
      and its treatment.

PMID- 22863829
TI  - Pediatric emergency medicine: legal briefs.

PMID- 22863830
TI  - ECGs in the ED.

PMID- 22863831
TI  - Commentary on "benign afebrile convulsions in the course of mild acute
      gastroenteritis".

PMID- 22863832
TI  - Delayed forehead hematoma.

PMID- 22863833
TI  - Response to "the first published case of a pediatric diphenhydramine overdose
      whose electrocardiogram shows terminal 40-millisecond frontal plane QRS axis
      deviation".

PMID- 22863834
TI  - Association of changes in body fatness and fatty acid composition of plasma
      phospholipids during early puberty in Japanese children.
AB  - AIMS: Plasma fatty acid composition can change with age, reflecting diet and
      levels of desaturating enzymes such as stearoyl-CoA desaturase (SCD), delta-6
      desaturase (D6D) and delta-5 desaturase (D5D), which contribute to the
      development of insulin resistance. This study analyzed longitudinal changes in
      fatty acid composition in Japanese children during early puberty and the
      association between changes in desaturase indices and changes in body fatness and
      insulin resistance. METHODS: The study included 77 children (38 boys and 39
      girls) aged 9.6+/-0.5 years. Relative weight (RW) and waist-to-height ratio
      (WHtR) were determined. The fatty acid composition of plasma phospholipids was
      analyzed by gas chromatography, and the desaturase indices were calculated: SCD
      (16:1n-7/16:0: SCD16 and 18:1n-9/18:0: SCD18), D6D (20:3n-6/18:2n-6) and D5D
      (20:4n-6/20:3n-6) in 2006 and 2009. RESULTS: Obese children showed higher dihomo
      gamma linolenic acid (DGLA; 20:3n-6), a higher D6D index and lower D5D index than
      non-obese children. Longitudinal changes in fatty acid com-position were
      generally similar in both sexes. Increased D6D index and DGLA and decreased D5D
      index were significantly associated with increased WHtR in boys and girls. In
      addition, increased D6D index was associated with an increased homeostasis model
      of assessment ratio (HOMA-R) only in girls. CONCLUSION: The change in abdominal
      adiposity is a determinant of longitudinal changes in D6D and D5D indices and
      DGLA during early puberty.

PMID- 22863835
TI  - Adrenergic nerves govern circadian leukocyte recruitment to tissues.
AB  - The multistep sequence leading to leukocyte migration is thought to be locally
      regulated at the inflammatory site. Here, we show that broad systemic programs
      involving long-range signals from the sympathetic nervous system (SNS) delivered
      by adrenergic nerves regulate rhythmic recruitment of leukocytes in tissues.
      Constitutive leukocyte adhesion and migration in murine bone marrow (BM) and
      skeletal-muscle microvasculature fluctuated with circadian peak values at night.
      Migratory oscillations, altered by experimental jet lag, were implemented by
      perivascular SNS fibers acting on beta-adrenoreceptors expressed on
      nonhematopoietic cells and leading to tissue-specific, differential circadian
      oscillations in the expression of endothelial cell adhesion molecules and
      chemokines. We showed that these rhythms have physiological consequences through
      alteration of hematopoietic cell recruitment and overall survival in models of
      septic shock, sickle cell vaso-occlusion, and BM transplantation. These data
      provide unique insights in the leukocyte adhesion cascade and the potential for
      time-based therapeutics for transplantation and inflammatory diseases.

PMID- 22863837
TI  - Reconstruction with pasteurized autograft for primary malignant bone tumor of
      distal tibia.
AB  - OBJECTIVE: The aim of this study was to assess the specific protocol for the
      treatment of primary malignant bone tumors of distal tibiae in a group of
      patients for limb salvage, with wide "en bloc" intra-articular excision and
      reconstruction of the defect with recycled pasteurized autograft, which was
      stabilized using an internal fixator. METHODS: Between 1994 and 2009, ten
      patients (three females and seven males) at a mean age of 26.5 years old were
      treated for malignant bone tumors of the distal tibiae with "en bloc" intra
      articular excision and ankle arthrodesis using recycled pasteurized autograft.
      Nine cases were histopathologically diagnosed as high-grade osteosarcoma, and one
      case as invasive osteoblastoma. All bone tumors were staged according to
      Enneking's criteria with two stages IIA cases, and eight stages IIB cases.
      RESULTS: At a mean follow-up of 81 months, the mean postoperative functional
      score was 74.3%. All the patients had bony union at the last follow-up. Six
      patients required secondary iliac crest cancellous bone grafting at the proximal
      end to achieve union. The mean time for graft union was 18.9 months, and the
      average union time of the proximal junctions was longer than that of the distal
      junctions. Superficial infection occurred in two patients (20.0%), which were
      resolved by changing dress. There was no deep infection or graft fracture during
      the entire procedure. CONCLUSIONS: The use of pasteurized bone graft for primary
      malignant bone tumors of distal tibia indicated a satisfactory outcome, with
      regard to graft survival, complications, and functional results. A pasteurized
      auto-graft can be an easily accessible and economical alternative of high
      efficiency for the usual reconstruction modalities.

PMID- 22863836
TI  - Histo-cytometry: a method for highly multiplex quantitative tissue imaging
      analysis applied to dendritic cell subset microanatomy in lymph nodes.
AB  - Flow cytometry allows highly quantitative analysis of complex dissociated
      populations at the cost of neglecting their tissue localization. In contrast,
      conventional microscopy methods provide spatial information, but visualization
      and quantification of cellular subsets defined by complex phenotypic marker
      combinations is challenging. Here, we describe an analytical microscopy method,
      "histo-cytometry," for visualizing and quantifying phenotypically complex cell
      populations directly in tissue sections. This technology is based on multiplexed
      antibody staining, tiled high-resolution confocal microscopy, voxel gating,
      volumetric cell rendering, and quantitative analysis. We have tested this
      technology on various innate and adaptive immune populations in murine lymph
      nodes (LNs) and were able to identify complex cellular subsets and phenotypes,
      achieving quantitatively similar results to flow cytometry, while also gathering
      cellular positional information. Here, we employ histo-cytometry to describe the
      spatial segregation of resident and migratory dendritic cell subsets into
      specialized microanatomical domains, suggesting an unexpected LN demarcation into
      discrete functional compartments.

PMID- 22863838
TI  - Macrophage impairment produced by Fc receptor gamma deficiency plays a principal
      role in the development of lipoprotein glomerulopathy in concert with apoE
      abnormalities.
AB  - BACKGROUND: To obtain a clear understanding of the pathogenesis of lipoprotein
      glomerulopathy (LPG), we studied the role of the deficiency of Fc receptor gamma
      chain (FcRgamma) for the development of LPG in concert with apolipoprotein E
      (apoE) abnormalities. METHODS: We generated apoE and FcRgamma double-knockout
      (FcRgamma/apoE-KO) mice, and subsequently introduced several kinds of human
      recombinant apoE genes. At 21 days after infection, the mice were sacrificed and
      histologically examined. Peritoneal macrophages were evaluated for their response
      to modified lipids. RESULTS: In the FcRgamma/apoE-KO mice, the human apoE3
      injected mice showed the most drastic LPG-like changes, as well as prominent
      hypertriglyceridemia. Meanwhile, relative to the human apoE3-injected mice, the
      FcRgamma/apoE-KO mice showed greater lipoprotein deposition and less macrophage
      infiltration into the mesangial area. Moreover, the peritoneal macrophages in the
      apoE/FcRgamma-KO mice were impaired in lipid uptake and secretion of the
      cytokines monocyte chemotactic protein-1 and regulated upon activation, normal T
      cell expressed and secreted, after the uptake of oxidized low-density
      lipoprotein. CONCLUSIONS: These results suggest that the impairment of macrophage
      function resulting from FcRgamma deficiency plays a principal role in the
      development of LPG in the presence of apoE abnormalities.

PMID- 22863839
TI  - Urine podocin:nephrin mRNA ratio (PNR) as a podocyte stress biomarker.
AB  - BACKGROUND: Proteinuria and/or albuminuria are widely used for noninvasive
      assessment of kidney diseases. However, proteinuria is a nonspecific marker of
      diverse forms of kidney injury, physiologic processes and filtration of small
      proteins of monoclonal and other pathologic processes. The opportunity to develop
      new glomerular disease biomarkers follows the realization that the degree of
      podocyte depletion determines the degree of glomerulosclerosis, and if
      persistent, determines the progression to end-stage kidney disease (ESKD).
      Podocyte cell lineage-specific mRNAs can be recovered in urine pellets of model
      systems and in humans. In model systems, progressive glomerular disease is
      associated with decreased nephrin mRNA steady-state levels compared with podocin
      mRNA. Thus, the urine podocin:nephrin mRNA ratio (PNR) could serve as a useful
      progression biomarker. The use of podocyte-specific transcript ratios also
      circumvents many problems inherent to urine assays. METHODS: To test this
      hypothesis, the human diphtheria toxin receptor (hDTR) rat model of progression
      was used to evaluate potentially useful urine mRNA biomarkers. We compared
      histologic progression parameters (glomerulosclerosis score, interstitial
      fibrosis score and percent of podocyte depletion) with clinical biomarkers [serum
      creatinine, systolic blood pressure (BP), 24-h urine volume, 24-h urine protein
      excretion and the urine protein:creatinine ratio(PCR)] and with the novel urine
      mRNA biomarkers. RESULTS: The PNR correlated with histologic outcome as well or
      better than routine clinical biomarkers and other urine mRNA biomarkers in the
      model system with high specificity and sensitivity, and a low coefficient of
      assay variation. CONCLUSIONS: We concluded that the PNR, used in combination with
      proteinuria, will be worth testing for its clinical diagnostic and decision
      making utility.

PMID- 22863840
TI  - Prevention of nausea and vomiting associated with stem cell transplant: results
      of a prospective, randomized trial of aprepitant used with highly emetogenic
      preparative regimens.
AB  - Uncontrolled delayed nausea and vomiting remains a problem after high-dose
      preparative regimens used for autologous and allogeneic hematopoietic stem cell
      transplants. Recently, aprepitant was approved for highly and moderately
      emetogenic chemotherapy, and, in particular, is effective for decreasing delayed
      emesis. To evaluate its safety and efficacy in the transplantation setting, we
      performed a randomized, placebo-controlled, phase 3 trial of aprepitant in
      combination with ondansetron and dexamethasone in patients treated with ablative
      preparative regimens. Patients were randomized to receive oral aprepitant or
      placebo daily with oral ondansetron and dexamethasone during and for 3 days after
      the completion of the preparative regimen in this prospective randomized, double
      blind study. The primary objective was complete response (CR) rate, defined as no
      emesis with no or mild nausea. Other endpoints included number of emetic
      episodes, nausea severity assessed using a 100-mm visual analog scale (VAS), the
      need for rescue antiemetics, and transplantation outcome, including regimen
      related toxicity. One hundred eighty-one patients were randomized and 179
      patients were eligible for analysis. Overall, CR rates were 81.9% for the
      aprepitant and 65.8% for the placebo arms (P < .001). Percentages of patients
      with no emesis all days were 73.3% for aprepitant and 22.5% placebo (P < .001).
      Mean VAS scores were 16.6 mm aprepitant and 16.9 mm placebo (NS), and there were
      no differences in the amount of rescue antiemetics used, regimen related
      toxicity, engraftment, or transplantation outcome. Aprepitant in combination with
      dexamethasone and ondansetron significantly decreased emesis and significant
      nausea, whereas not increasing RRT or affecting short-term survival but had no
      significant impact on the use of PRN antiemetics, or overall VAS nausea scores.

PMID- 22863841
TI  - Haploidentical transplantation using T cell replete peripheral blood stem cells
      and myeloablative conditioning in patients with high-risk hematologic
      malignancies who lack conventional donors is well tolerated and produces
      excellent relapse-free survival: results of a prospective phase II trial.
AB  - Haploidentical hematopoietic stem cell transplant (HSCT) provides an opportunity
      for nearly all patients to benefit from HSCT. We conducted a trial of
      haploidentical T cell replete allografting using a busulfan-based myeloablative
      preparative regimen, peripheral blood stem cells (PBSCs) as the graft source, and
      posttransplantation cyclophosphamide (Cy). Eligibility was limited to patients at
      high risk of relapse after nonmyeloablative haploidentical bone marrow transplant
      (BMT). Twenty patients were enrolled in the study (11 with relapsed/refractory
      disease and 9 who underwent transplantation while in remission and considered
      standard risk). Donor engraftment occurred in all 20 patients with full donor T
      cell and myeloid chimerism by day +30. The cumulative incidence of grades II-IV
      and III-IV acute graft-versus-host disease (aGVHD) was 30% and 10%, respectively.
      The cumulative incidence of chronic GVHD (cGVHD) was 35%. Nonrelapse mortality
      (NRM) at 100 days and 1 year was 10% for all patients and 0% for standard-risk
      patients. With a median follow-up of 20 months, the estimated 1-year overall
      survival (OS) and disease-free survival (DFS) was 69% and 50%, respectively, for
      all patients, and 88% and 67% for standard-risk patients. Myeloablative
      haploidentical HSCT is associated with excellent rates of engraftment, GVHD, NRM,
      and DFS, and is a valid option in patients with high-risk malignancies who lack
      timely access to a conventional donor.

PMID- 22863843
TI  - Dietary genistein induces sex-dependent effects on murine body weight, serum
      profiles, and vascular function of thoracic aortae.
AB  - BACKGROUND: The influence on, or interaction of, sex and dietary genistein on
      serum markers of cardiovascular health and cardiovascular function remain
      unclear. OBJECTIVES: Our purpose was to examine the effects of a genistein
      containing diet (600 mg/kg food) (600G) and a genistein-free diet (0G), on
      cardiovascular risk parameters of male and female mice. METHODS: C57BL/6J mice
      were fed the diets for 1 month, after which time blood pressure, serum markers,
      and in vitro vascular reactivity was measured. RESULTS: Males fed the 600G diet
      gained significantly less weight than males fed the 0G diet (by 1.71 g); diet had
      no effect on female weight gain. Males fed the 600G diet also exhibited
      significantly elevated serum insulin (2.9 [0.5] vs 1.8 [0.4] ng/dL), and
      decreased serum glucose (0.15 [0.01] vs 0.24 [0.02] ng/dL) levels, resulting in a
      significant increase in the ratio of insulin to glucose; insulin and glucose
      levels were not changed by dietary genistein in females. Arterial pressure
      measurements from 0G-fed males were lower than other groups. However, basal
      vascular reactivity of isolated aortic rings was significantly increased by the
      600G diet in both males (from 0.55 [0.03] to 0.94 [0.18] g) and females (from
      0.45 [0.04] to 0.78 [0.09] g). Aortic wall thickness was not affected by diet.
      Norepinephrine-mediated contractility was also greater in aortic rings of male
      and female mice fed the 600G diet, and differences from the 0G diet persisted in
      the presence of L-NG-nitroarginine methyl ester but were completely accounted for
      by increased basal reactivity. CONCLUSION: Our data indicate that 1 month of a
      600G or 0G diet significantly alters vascular function independent of sex. In
      contrast, sex-dependent differences exist in well-established serum markers of
      cardiovascular health and disease.

PMID- 22863844
TI  - Induction of G1 arrest and apoptosis in human cancer cells by crebanine, an
      alkaloid from Stephania venosa.
AB  - In this study, we focused the effects of crebanine, an alkaloid isolated from the
      tuber of Stephania venosa, on various human cancer cells. Crebanine treatment was
      found to significantly inhibit the proliferation of human leukemic cells (HL-60,
      U937 and K562), human fibrosarcoma cells (HT1080) and cervix cancer cell lines
      (KB-3-1 and KB-V1), of which HL-60 cells were the most sensitive to its
      treatment. In contrast, crebanine caused much less toxicity in human normal
      fibroblast cells. Our results demonstrated that crebanine mediated cell cycle
      arrest at G0/G1 phase and this was associated with down-regulation of cyclins A
      and D. In addition, crebanine induced apoptosis, which was detected by
      observation of the membrane phospholipid exposure in flow cytometry. Its
      induction of apoptosis was accompanied by an increase in cleavage of caspase-3, 
      8, -9 and poly(ADP-ribose) polymerase (PARP), and was attributable to the
      augmentation of Bax/Bcl proteins level. Crebanine also decreased mitochondrial
      membrane potential. Taken together, crebanine exerts anti-proliferative effects
      on human cancer cells through the induction of cell cycle arrest at the G1 phases
      and apoptosis. Our results suggest that crebanine is a promising new candidate as
      a chemotherapeutic agent for cancer therapy.

PMID- 22863842
TI  - Late effects in hematopoietic cell transplant recipients with acquired severe
      aplastic anemia: a report from the late effects working committee of the center
      for international blood and marrow transplant research.
AB  - With improvements in hematopoietic cell transplant (HCT) outcomes for severe
      aplastic anemia (SAA), there is a growing population of SAA survivors after HCT.
      However, there is a paucity of information regarding late effects that occur
      after HCT in SAA survivors. This study describes the malignant and nonmalignant
      late effects in survivors with SAA after HCT. A descriptive analysis was
      conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006
      reported to the Center for International Blood and Marrow Transplant Research
      (CIBMTR). The prevalence and cumulative incidence estimates of late effects are
      reported for 1-year HCT survivors with SAA. Of the HCT recipients, 1176 (68.5%)
      and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated
      donor (URD) HCT, respectively. The median age at the time of HCT was 20 years.
      The median interval from diagnosis to transplantation was 3 months for MSD HCT
      and 14 months for URD HCT. The median follow-up was 70 months and 67 months for
      MSD and URD HCT survivors, respectively. Overall survival at 1 year, 2 years, and
      5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73%
      (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6%
      had 1 late effect and 1% had multiple late effects. For 1-year survivors of URD
      HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of
      MSD HCT, the cumulative incidence estimates of developing late effects were all
      <3% and did not increase over time. In contrast, for recipients of URD HCT, the
      cumulative incidence of developing several late effects exceeded 3% by 5 years:
      gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI:
      4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95%
      CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that
      all patients undergoing HCT for SAA remain at risk for late effects, must be
      counseled about, and should be monitored for late effects for the remainder of
      their lives.

PMID- 22863845
TI  - Synthesis, antitumor and antimicrobial testing of some new thiopyrimidine
      analogues.
AB  - The synthesis of some new 4-chloro-pyrimidine-5-carbonitriles (3b-d), 4
      substituted-amino-pyrimidine-5-carbonitriles (4a-g), trioxo and dioxo
      thiazolo[3,2-a]pyrimidine-6-carbonitriles (5a-c and 6a-h) have been described.
      The obtained compounds were evaluated for their in-vitro antitumor activity. A
      single dose (10 uM) of the test compounds was used in the National Cancer
      Institute (NCI) 60 cell lines panel assay. Compounds 3c and 4f showed high
      inhibitory activity against leukemia, whereas, compounds 3b and 4d, g displayed
      moderate activity. On the other hand, all compounds were screened for their in
      vitro antibacterial and antifungal activities. Compounds 3d and 4b exhibited
      significant antibacterial activity against Staphylococcus aureus. Compound 4e
      showed two folds inhibitory activity against Entrobacter aerogener compared with
      the reference drug Tobramycin.

PMID- 22863846
TI  - Mixture designs to assess composition-structure-property relationships in SiO2
      CaO-ZnO-La2O3-TiO2-MgO-SrO-Na2O glasses: potential materials for embolization.
AB  - Embolization with micron-sized particulates is widely applied to treat uterine
      fibroids. The objective of this work was to develop mixture designs to predict
      materials composition-structure-property relationships for the SiO2-CaO-ZnO-La2O3
      TiO2-MgO-SrO-Na2O glass system and compare its fundamental materials properties
      (density and cytocompatibility), against a state-of-the-art embolic agent
      (contour polyvinyl alcohol) to assess the potential of these materials for
      embolization therapies. The glass structures were evaluated using 29Si MAS NMR to
      identify chemical shift and line width; the particulate densities were determined
      using helium pycnometry and the cell viabilities were assessed via MTT assay.
      29Si MAS NMR results indicated peak maxima for each glass in the range of -82.3
      ppm to -89.9 ppm; associated with Q2 to Q3 units in silicate glasses. All
      experimental embolic compositions showed enhanced in vitro compatibility in
      comparison to Contour PVA with the exceptions of ORP9 and ORP11 (containing no
      TiO2). In this study, optimal compositions for cell viability were obtained for
      the following compositional ranges: 0.095-0.188 mole fraction ZnO; 0.068-0.159
      mole fraction La2O3; 0.545-0.562 mole fraction SiO2 and 0.042-0.050 mole fraction
      TiO2. To ensure ease of producibility in obtaining good melts, a maximum loading
      of 0.068 mole fraction La2O3 is required. This is confirmed by the desirability
      approach, for which the only experimental composition (ORP5) of the materials
      evaluated was presented as an optimum composition; combining high cell viability
      with ease of production (0.188 mole fraction ZnO; 0.068 mole fraction La2O3;
      0.562 mole fraction SiO2 and 0.042 mole fraction TiO2).

PMID- 22863847
TI  - Perspectives on non-clinical safety evaluation of drug metabolites through the
      JSOT workshop.
AB  - The prompt and appropriate safety assessment of drug metabolite(s) was mentioned
      in regulatory guidances such as an International Conference on Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
      guidance, entitled "Guidance on Non-clinical  Safety Studies for the Conduct of
      Human Clinical Trials and Marketing Authorization for Pharmaceuticals" (ICH
      M3(R2)) implemented in January 1 of 2011 in Japan, and has become a significant
      issue in the drug development. Upon release of ICH M3(R2) Step 4, a survey was
      conducted between March and April 2010 on the safety assessment of drug
      metabolites in 63 member companies of the Japan Pharmaceutical Manufacturers
      Association (JPMA). The Pharmacokinetics Team in the Non-Clinical Evaluation
      Expert Committee in JPMA conducted a questionnaire survey and compiled the
      results to comprehend how safety of drug metabolites are currently assessed at
      research-based pharmaceutical companies in Japan. The assessment of "Metabolites
      in Safety Testing" (MIST) can be divided into three stages based on the research
      purpose as follows: MIST 1 is a stage of estimating human drug metabolites and
      predicting their potential risks, MIST 2 is a stage of deciding the necessity for
      non-clinical safety studies, and MIST 3 is a stage of conducting non-clinical
      safety studies. In this paper, we propose typical approaches on safety assessment
      of metabolites that meet the purpose of each stage, considering the current level
      of scientific technology. Our proposals are based on the results from our survey
      and a symposium about the safety assessment of drug metabolites at the 37th
      annual meeting of the Japanese Society of Toxicology held in June 2010.

PMID- 22863848
TI  - Oxidative stress in the testis induced by tamoxifen and its effects on early
      embryo development in isogenic mice.
AB  - Oxidative stress induced by tamoxifen (TAM) in male testis and its effects on
      fertility and early embryo development were investigated. TAM was orally
      administered for 4 weeks repeatedly to two isogenic male mice strains, inbred
      strain of C57BL/6J (B6) mice and hybrid strain of C57BL/6J x CBA F1 (B6CBAF1)
      mice. Oxidative stress in mice testis was measured based on the level of lipid
      peroxidation (LPO). The LPO level was significantly increased in inbred strain of
      B6 mice (p < 0.05), but not hybrid strain of B6CBAF1 mice. Paternal exposure to
      TAM led to a significant decrease in the fertilization rate in B6 mice (p <
      0.05), but not their B6CBAF1 counterparts. Interestingly, TAM had no impact on
      the cell number and apoptosis status in blastocysts. These results indicate that
      susceptibility to TAM-induced oxidative stress in the testis differs between
      isogenic mice strains, and genetic variations play an important role in promoting
      differential degrees of toxic response.

PMID- 22863849
TI  - Delayed effects of single neonatal subcutaneous exposure of low-dose 17alpha
      ethynylestradiol on reproductive function in female rats.
AB  - Delayed effects of exposure to small amounts of estrogenic compounds during the
      critical period of brain sexual differentiation were investigated by subcutaneous
      treatment of female Sprague-Dawley rats with 0 (vehicle control), 0.08, 0.4, or 2
      ug/kg of 17alpha-ethynylestradiol (EE) on postnatal day (PND) 1. The treatment
      did not affect growth and development of the treated animals, and the timings of
      vaginal opening were similar between the EE-treated and control groups. The
      animals were periodically examined for the estrous cycle from postnatal week
      (PNW) 8-9 to PNW 32-33. Patterns of the estrous cycle were similar among the
      groups until PNW 17. None of the control animals showed persistent estrus until
      PNW 33. The animals treated with 0.4 ug/kg or more EE showed persistent estrus
      from PNW 20. The alteration was reflected in the number of days judged as
      proestrus or estrus, and was found to gradually increase in the EE-treated
      groups. At necropsy on PNW 32-33, ovulation was not confirmed in most EE-treated
      animals, even on the day of estrus. In addition, sporadic milk accumulations were
      observed in the mammary gland of the EE-treated animals. Histological evaluation
      revealed cystic follicle formation in the EE-treated ovaries and also revealed
      hyperplasia of mammary glands. Furthermore, ovaries from the animals showing
      persistent estrus lacked corpus luteum, indicating long-term anovulation. These
      results clearly show that single exposure to EE during the critical period of
      brain sexual differentiation can exert effects on reproductive functions at a
      later period in rats.

PMID- 22863850
TI  - Species differences in toxicokinetic parameters of glycidol after a single dose
      of glycidol or glycidol linoleate in rats and monkeys.
AB  - Glycidol fatty acid esters (GEs) have been identified as contaminants in refined
      edible oils. Although the possible release of glycidol (G) from GEs is a concern,
      little is known about the conversion of GEs to G in the human body. This study
      addressed the toxicokinetics of glycidol linoleate (GL) and G in male Crl:CD(SD)
      rats and cynomolgus monkeys. Equimolar amounts of GL (341 mg/kg) or G (75 mg/kg)
      were administered by gavage to each animal. G was found in both species after the
      G and GL administration, while plasma GL concentrations were below the lower
      limit of quantification (5 ng/ml) in both species. In rats, the administration of
      GL or G produced similar concentration-time profiles for G. In monkeys, the
      C(max) and AUC values after GL administration were significantly lower than those
      after G administration. The oral bioavailability of G in monkeys (34.3%) was
      remarkably lower than that in rats (68.8%) at 75 mg/kg G administration. In
      addition, plasma G concentrations after oral administration at three lower doses
      of GL or G were measured in both species. In monkeys, G was detected only at the
      highest dose of G. In contrast, the rats exhibited similar plasma G concentration
      time profiles after GL or G administration with significantly higher G levels
      than those in monkeys. In conclusion, these results indicate that there are
      remarkable species differences in the toxicokinetics of GEs and G between rodents
      and primates, findings that should be considered when assessing the human risk of
      GEs.

PMID- 22863851
TI  - Functional characterization and substrate specificity of a novel gene encoding
      zinc finger-like protein, ZfLp, in Xenopus laevis oocytes.
AB  - In the present study, we isolated and determined the pharmacological
      characteristics of a novel gene encoding the zinc finger-like protein (ZfLp). The
      isolated cDNA consisted of 1,581 base pairs that encoded a 526-amino acid
      protein. The amino acid sequence of ZfLp is 96% identical to that of zinc finger
      protein 415 isoform 5 (ZNF415-5). Reverse-transcription (RT)-polymerase chain
      reaction (PCR) analysis revealed that the ZfLp mRNA is expressed in the breast,
      lung, stomach, small intestine colon and ovary, but not in the liver. When
      expressed in Xenopus laevis oocytes, ZfLp mediated the high affinity transport of
      [(3)H]paclitaxel (taxol) in a sodium-independent manner (K(m) = 336.7 +/- 190.0
      nM). The uptake of [(3)H]paclitaxel (taxol) by ZfLp was trans-stimulated by
      glutarate and glutathione (GSH). A cis-inhibition experiment revealed that ZfLp
      mediated transport of [(3)H]paclitaxel (taxol) is inhibited by several organic
      solutes specifically clotrimazole. Using several clotrimazole derivatives, we
      found that N-benzylimidazole would be a minimum unit for producing the inhibition
      of ZfLp-mediated drug uptake. Our results may provide insights into the novel
      role of soluble protein, such as ZNF, in the human body. Our results, therefore,
      would be expected to facilitate research on the novel role of ZNFs and on the
      discovery of novel drugs for targeting ZNF-related proteins such as ZfLp.

PMID- 22863852
TI  - In vivo genotoxicity of 1-methylnaphthalene from comprehensive toxicity studies
      with B6C3F1 gpt delta mice.
AB  - 1-Methylnaphthalene (1-MN), a constituent of the polycyclic aromatic hydrocarbons
      (PAHs), is a lung carcinogen in mice. However, conventional genotoxicity tests
      such as the Ames test and sister chromatid exchange (SCE) test have yielded
      equivocal results. In the present study, the in vivo genotoxicity of 1
      methylnaphthalene (1-MN) together with its toxicological profile was investigated
      in a 13-week repeated dose toxicity study of 1-MN using B6C3F1 gpt delta mice. In
      the serum biochemistry, significant increases in AST and ALP were observed in
      males of the 0.15% 1-MN group. From histopathological examination, the incidence
      of single cell necrosis in the liver was significantly increased in males of the
      0.15% 1-MN group; however, no changes were observed in the lungs, the target
      organ of 1-MN. In an in vivo mutation assay, no changes in mutant frequencies of
      gpt and red/gam (Spi-) in lung DNA of 1-MN treated mice were observed at 13
      weeks. In addition, there were no significant differences in the proliferating
      cell nuclear antigen (PCNA)-positive ratios in bronchiolar epithelial cells among
      the groups for either sex. These results suggest that 1-MN at a carcinogenic dose
      not induce overt toxicity for any organs and has no in vivo genotoxicity in the
      lungs.

PMID- 22863853
TI  - Predictive genomic biomarkers for drug-induced nephrotoxicity in mice.
AB  - The present study aimed to establish candidate biomarker genes for the early
      detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity
      caused by polyene macrolides. Comprehensive gene expression changes were
      evaluated using microarrays in a mouse model in which acute nephrotoxicity was
      induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated
      genes identified through microarray analysis of kidney tissue of Fungizone
      treated mice included several genes that have been reported as nephrotoxicity
      biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity
      biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice
      was evaluated further through expression profiling under several experimental
      conditions using real time RT-PCR. Expression of genes encoding kidney injury
      molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted
      phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin,
      amphotericin B methyl ester, and liposomal amphotericin B, and their area under
      the ROC curve values were more than 0.95. These genes were more sensitive at
      detecting nephrotoxicity than traditional clinical chemistry and histopathology
      parameters. This study provides novel evidence that these nephrotoxicity
      biomarker genes identified are translatable to mice, and that they are useful for
      early and sensitive detection of nephrotoxicity.

PMID- 22863854
TI  - Effect of exposure to volatile organic compounds (VOCs) on airway inflammatory
      response in mice.
AB  - Volatile organic compounds (VOCs) are the main substances causing multiple
      chemical sensitivity reactions in human. The effects of single VOCs exposure on
      airway inflammatory responses in mice lung have been reported. Previous studies
      have demonstrated the role of reactive oxygen species (ROS) in lung inflammation
      induced by single VOCs inhalation. However, effects of VOCs exposure on NO
      signaling and neurological signaling pathways in airway remain less clear. We
      exposed male Kunming mice to filtered air (0) and four types of VOCs mixture
      (formaldehyde, benzene, toluene, and xylene) treated air. Group 1 is 1.0, 1.1,
      2.0 and 2.0 mg/m(3), group 2 is 3.0, 3.3, 6.0 and 6.0 mg/m(3), group 3 is 5.0,
      5.5, 10.0 and 10.0 mg/m(3), group 4 is 10.0, 11.0, 20.0 and 20.0 mg/m(3), which
      respectively corresponded to 10, 30, 50 and 100 times of indoor air quality
      standard in China 2 hr per day, 5 days per week, for 2 weeks in the whole body
      exposure chamber. One day following VOCs exposure, we collected lung,
      bronchoalveolar lavage fluid (BALF) from each mouse and examined oxidative stress
      markers, cellular infiltration and production of cytokines, neurotrophin and
      substance P. We found that VOCs exposure influenced significantly NOS activity,
      GSH, or IL-6 concentration. The number of total cells, macrophages and
      eosinophils increased significantly in group 4. In addition, the production of
      interferon-gamma (IFN-gamma) and substance P were significantly decreased. In
      contrast, neurotrophin-3 production in BALF was significantly increased in group
      3 and 4. Our findings suggest that NO signaling pathways may induce airway
      inflammatory in short term VOCs exposure mice and the airway inflammatory
      response may be modulated by neurological signaling.

PMID- 22863855
TI  - Increased expression of aquaporin-4 with methylmercury exposure in the brain of
      the common marmoset.
AB  - The relationship between methylmercury (MeHg) exposure and aquaporin (AQP)
      expression in the brain is currently unknown. To investigate this, we used a
      common marmoset model of acute MeHg exposure to examine AQP1, AQP4 and AQP11 gene
      expression. MeHg (1.5 mg Hg/kg/day p.o.) was given to three marmosets for 14
      days, followed by 14 days without. All treated marmosets showed slight akinesia
      before sacrifice. In the frontal lobe, occipital lobe and cerebellum, total
      mercury concentrations following MeHg administration were 26.7, 31.4, and 22.6
      ug/g, respectively. Slight apoptosis was observed in the occipital lobe.
      Immunohistochemistry showed increased expression of glial fibrillary acidic
      protein, its mRNA and Iba1 with MeHg, indicating that neuronal injury activated
      astrocytes and microglia. There was no significant difference between control and
      MeHg-administered groups in AQP1 protein or AQP11 mRNA in the frontal lobe,
      occipital lobe or cerebellum. The ratio of AQP4 mRNA expression in MeHg
      administered marmosets to the mean AQR4 expression in the controls (n = 3) were
      1.3, 1.5 and 1.2, 1.7, 1.9 and 1.5, and 1.5, 1.6 and 1.2 for the frontal lobe,
      occipital lobe and cerebellum, respectively. Western blotting showed
      significantly increased AQP4 protein in the occipital lobe and cerebellum with
      MeHg administration, but no obvious up-regulation in the frontal lobe.
      Immunofluorescence analysis with double staining revealed low AQP4 expression in
      the cell body of reactive astrocytes in the MeHg-administered group. These
      results indicate that AQP4 expression might be stimulated by MeHg exposure in
      astrocytes in the occipital lobe and cerebellum, suggesting a role for AQP4 in
      MeHg neurotoxicity via astrocyte dysfunction.

PMID- 22863856
TI  - Distribution of mercury in metallothionein-null mice after exposure to mercury
      vapor: amount of metallothionein isoform does not affect accumulation of mercury
      in the brain.
AB  - To examine the contribution of metallothionein (MT) to mercury accumulation in
      mouse tissues, 129 strain female mice and MT null mice were exposed to metallic
      mercury vapor at a sub-toxic level, and Hg levels in the brain, kidney and liver
      were determined on 1, 3 and 7 days after the exposure. After exposure to mercury
      vapor, significant Hg accumulation was observed in the brains of wild-type and MT
      I/II null and MT-III null mice, as well as in the liver and kidneys. No strain
      difference was observed in the tissue Hg accumulations 24 hr after the exposure
      except for the kidneys, where the highest accumulation was found in MT-III null
      mice. Although the brains of MT-III null mice showed slightly higher Hg
      accumulation than the other two strains, no significant difference was observed
      except in the cerebrum on Day 7. Gel chromatograms of cerebrum soluble fractions
      revealed that a significant amount of Hg existed as an MT-bound form in all the
      mouse strains. On the other hand, MT-bound Hg was found as a minor fraction in
      soluble fractions of the kidneys and livers in wild-type and MT-III null mice.
      Despite a significant strain difference in total MT levels in the cerebrum, there
      was no difference among the three strains in the amount of Hg accumulated in the
      cerebrum and its distribution rates in MT fractions. The present study
      demonstrated that brain uptake of Hg(0) and its accumulation as Hg(2+) did not
      depend on the amount of MT isoform in the tissue, at least in the early phase.

PMID- 22863857
TI  - Methamphetamine causes anorexia in Drosophila melanogaster, exhausting metabolic
      reserves and contributing to mortality.
AB  - Methamphetamine (MA) appears to produce neurotoxic effects, in part, through
      disruptions of energy metabolism. A recent study of the whole-body proteome of
      Drosophila melanogaster showed many changes in energy metabolism-related
      proteins, leading us to hypothesize that MA toxicity may cause whole-body
      disruptions of energy metabolism. To test this, we monitored the response of
      energy reserves and other metabolites to MA-exposure with and without the
      addition of dietary glucose. We also monitored changes in feeding behavior,
      locomotor activity and respiration rates associated with MA-exposure to
      investigate how MA affects energy balance. We observed that glycogen and
      triglyceride levels decreased dramatically within 48 hr of MA-exposure,
      indicating a strongly negative caloric balance. Behavioral assays revealed that
      MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold
      increase in locomotion. Caloric expenditure decreased with MA-exposure,
      apparently due to a compensatory decrease in resting metabolism, showing that
      anorexia was the primary driver of the negative caloric balance. Additionally, we
      observed that glucose supplementation of MA-containing diet increased glycogen
      reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We
      conclude that dietary sugar supplementation enhances survivorship by partially
      compensating for decreased caloric intake resulting from MA-induced anorexia. The
      observation that MA produces similar behavioral changes in Drosophila and humans,
      i.e. increased locomotor activity and anorexia, further supports the use of
      Drosophila as a model organism for the study of the effects of MA.

PMID- 22863858
TI  - Evaluation of DNA microarray results in the Toxicogenomics Project (TGP)
      consortium in Japan.
AB  - An important technology used in toxicogenomic drug discovery research is the
      microarray, which enables researchers to simultaneously analyze the expression of
      a large number of genes. To build a database and data analysis system for use in
      assessing the safety of drugs and drug candidates, in 2002 we conducted a 5-year
      collaborative study in the Toxicogenomics Project (TGP1) in Japan. Experimental
      data generated by such studies must be validated by different laboratories for
      robust and accurate analysis. For this purpose, we conducted intra- and inter
      laboratory validation studies with participating companies in the second
      collaborative study in the Toxicogenomics Project (TGP2). Gene expression in the
      liver of rats treated with acetaminophen (APAP) was independently examined by the
      participating companies using Affymetrix GeneChip microarrays. The intra- and
      inter-laboratory reproducibility of the data was evaluated using hierarchical
      clustering analysis. The toxicogenomics results were highly reproducible,
      indicating that the gene expression data generated in our TGP1 project is
      reliable and compatible with the data generated by the participating
      laboratories.

PMID- 22863859
TI  - Apoptotic effects of satratoxin H is mediated through DNA double-stranded break
      in PC12 cells.
AB  - Satratoxin H is an important air- and food-borne mycotoxin, which has been
      implicated in human health damage. Satratoxin H is known to induce apoptosis as
      well as genotoxicity in PC12 cells. In the present study, we further investigated
      the mechanism of apoptotic effects of satratoxin H with focus on caspase-3 and
      poly-ADP-ribose polymerase (PARP) pathway. We also examined whether it induces
      DNA damage in PC12 cells. In the cells treated with satratoxin H, caspase-3 was
      cleaved in a time-dependent manner. Furthermore, satratoxin H induced cleavage of
      PARP, one of the downstream molecules of caspase-3. The cleavage was inhibited by
      SB203580, a p38 MAPK inhibitor, or SP600125, a JNK inhibitor. Satratoxin H,
      however, had no effect on expression levels of Bax and Bcl-2. Furthermore, the
      micronucleus assay revealed that satratoxin H induced chromosome break. Also,
      satratoxin H increased the level of phosphorylation of histone H2A, indicating
      that it caused DNA double-stranded breaks in PC12 cells. Meanwhile, no
      genotoxicity was detected with any of treatments carried out in the alkaline
      comet assay. These results imply that satratoxin H induces genotoxicity by DNA
      double-stranded break. Our results suggest a considerable potential for the
      genotoxic risk associated with the presence of satratoxin H.

PMID- 22863860
TI  - Proliferating effect of orotic acid through mTORC1 activation mediated by
      negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells.
AB  - Orotic acid (OA) is a tumor promoter of experimental liver carcinogenesis
      initiated by DNA reactive carcinogens, the molecular mechanisms of which have not
      been fully elucidated. OA increases cell proliferation and decreases apoptosis in
      serum-starved SK-Hep1 hepatocellular carcinoma cells, which may ascribe to the
      inhibition of AMP-activated protein kinase (AMPK) phosphorylation and thus
      activation of mammalian target of rapamycin complex 1 (mTORC1). The effects of OA
      on mTORC1 activation, cell proliferation, and cell-cycle progression to S and
      G2/M phases were completely reversed by rapamycin. Activation of AMPK by a
      constitutively active mutant or aminoimidazole carboxamide ribonucleotide (AICAR)
      rescued the effects of OA. In conclusion, OA increases the proliferation and
      decreases the starvation-induced apoptosis of SK-Hep1 cells via mTORC1 activation
      mediated by negative regulation of AMPK.

PMID- 22863861
TI  - Ototoxicity of cisplatin administered to guinea pigs via the round window
      membrane.
AB  - Animal models of ototoxicity represent an elementary tool in otolaryngologic
      research. Such models are usually created via the consecutive injection of
      ototoxic drugs or the co-administration of ethacrynic acid and low-dose ototoxic
      drugs. Injection via the round window membrane (RWM) is one approach that allows
      for local drug delivery into the inner ear. In this study, 47 guinea pigs
      received an injection of varying doses of cisplatin via the RWM, and data
      concerning the animals' auditory brainstem responses, hair cells, and spiral
      ganglion neurons were analyzed. Our results indicate the high efficiency and
      generally small reaction of the subjects, suggesting that the application of
      cisplatin via the RWM is an effective animal model for ototoxicity research.

PMID- 22863862
TI  - Methylglyoxal activates the human transient receptor potential ankyrin 1 channel.
AB  - Methylglyoxal (MG) is an endogenous carbonyl compound that is produced in large
      quantity under hyperglycemic conditions, which are believed to contribute to the
      development of diabetic neuropathy. However, the mechanism by which this occurs
      and the molecular targets of MG are unclear. In the present study, we
      investigated the effect of MG on transient receptor potential ankyrin 1 (TRPA1)
      activation in human TRPA1-expressing HEK293 cells. MG activated TRPA1-expressing
      HEK293 cells, but failed to activate human capsaicin-sensitive transient receptor
      potential vanilloid 1 (TRPV1)-expressing HEK293 cells or mock-transfected HEK293
      cells. MG also induced calcium (Ca(2+)) influx in a concentration-dependent
      manner, and the concentration-response curve indicates that the effect of MG has
      an EC(50) of 343.1 +/- 17.3 uM. Interestingly, the time course in the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) in human TRPA1-expressing HEK293
      showed considerable differences in response to MG and cinnamaldehyde.
      Furthermore, we examined four endogenous carbonyl compounds, including MG,
      glyceraldehyde, glycolaldehyde, and glyoxal; only MG notably activated TRPA1
      expressing HEK293 cells. These results may provide insight into the TRPA1
      mediated effects of MG on diabetic neuropathy.

PMID- 22863863
TI  - Bismuth protects against arsenite-induced inhibition of proteoglycan synthesis in
      cultured vascular endothelial cells.
AB  - Chronic ingestion of arsenic is associated with an increased risk of vascular
      disease such as atherosclerosis. Previously, we showed that arsenite inhibits the
      synthesis of general proteoglycans (PGs), which are key molecules in the
      progression of atherosclerosis, in vascular endothelial cells. In the present
      study, we investigated the effect of several metals on arsenite-induced
      inhibitory effect in endothelial cells. The results indicate that, after 24-hr
      incubation, the inhibition of PG synthesis caused by sodium arsenite was
      protected by bismuth nitrate but not zinc sulfate, manganese chloride, nickel
      chloride or cobalt chloride. The accumulation of arsenic in the cell layer was
      significantly decreased by bismuth after 12-hr incubation and that of bismuth was
      also decreased by arsenite. It was therefore suggested that the protective effect
      of bismuth against the inhibitory effect of arsenite on PG synthesis in vascular
      endothelial cells may be due, at least in part, to the decrease in cellular
      arsenic accumulation.

PMID- 22863864
TI  - Assessment of technical protocols for novel embryonic stem cell tests with
      molecular markers (Hand1- and Cmya1-ESTs): a preliminary cross-laboratory
      performance analysis.
AB  - The Hand1- and Cmya1-ESTs are novel short-term tests for embryotoxic chemicals
      using genetically engineering mouse ES cells for luciferase reporter gene assays.
      These ESTs allow convenient determination of differentiation toxicity and cell
      viability in a short duration with high throughput 96-well microplates for
      prediction of embryotoxicity of chemicals. To assess the Hand1-EST technical
      protocol, we firstly compared reporter gene assay and cytotoxicity test data for
      a representative compound (hydroxyurea) from four different laboratories with
      tests carried out under the same experimental conditions. Extensive
      investigations of the Hand1- and Cmya1-ESTs were then performed to explore
      reproducibility by comparing a set of 6 well-known test chemicals, including
      hydroxyurea, across the laboratories. The results gave good correspondence in all
      four laboratories, indicating that transferability, intra-laboratory variability
      and inter-laboratory variability of the present technical protocols of the ESTs
      were sufficient to conduct further validation studies.

PMID- 22863865
TI  - Distribution and chemical form of mercury in commercial fish tissues.
AB  - We analyzed total Hg concentrations in various tissue samples obtained from 7
      commercially available fish species. MeHg contents were also estimated for muscle
      and liver samples by a selective analysis of inorganic Hg. Among the tissues,
      high Hg accumulations were shown in liver, muscle, heart and spleen throughout
      all fish species. Carnivorous fish, such as scorpion fish, sea bream and Japanese
      whiting, tended to show higher Hg accumulations in the muscle, with the highest
      Hg levels being shown by scorpion fish. Although the liver was expected to show
      the highest Hg accumulations among tissues throughout all fish species, the
      highest accumulation in the liver was observed only in scorpion fish. In
      contrast, the muscle level was significantly higher than the liver in Pacific
      saury and Japanese whiting. MeHg accumulated in fish is considered to show a
      sustained increase throughout the life of the fish, due to its long biological
      half-life. In fact, in the present study, muscle Hg levels in Japanese whiting,
      Japanese flying fish, and halfbeak showed good correlations with body weights.
      However, such correlations were not clear in scorpion fish, sea bream, Jack
      mackerel and Pacific saury. Selective analyses of inorganic Hg levels revealed
      that most of the Hg (> 95%) in fish muscle existed as MeHg, while the rates of
      MeHg contents in the liver varied from 56% in scorpion fish to 84% in Jack
      mackerel. As a result, fish muscle showed the highest MeHg accumulations in all
      fish species examined. These results suggest that reliable information on total
      Hg contents in fish muscle might be sufficient to avoid the risk of MeHg exposure
      caused by eating fish, even when one consumes other tissues such as fish liver.

PMID- 22863866
TI  - Focused DNA microarray analysis for sex-dependent gene expression of drug
      metabolizing enzymes, transporters and nuclear receptors in rat livers and
      kidneys.
AB  - Cytochrome P450(CYP)s are known to show a sexual dimorphic expression in rat 
      livers. However, the comprehensive analysis for the sex-dependent gene
      expressions of drug metabolizing enzymes except for CYPs, transporters and
      nuclear receptors in rat livers and kidneys has not been investigated yet. The
      purpose of the present study was to identify the novel drug metabolizing and
      pharmacokinetics (DMPK)-related gene(s) which show the sex difference in the mRNA
      expressions in rat livers and kidneys. Total RNAs were prepared from livers and
      kidneys in both male and female rats (Crl:CD(SD) and Crlj:WI). A DNA microarray
      analysis using a "GeneSQUARE Multiple Assay DNA Microarray Drug Metabolism Gene
      Expression for Rat" was performed. DMPK-related genes which showed sex
      differences in the mRNA expression were identified in rat livers or kidneys.
      Especially, the female dominant expressions of UDP glucuronosyltransferase (UGT)
      s were seen in rat livers and kidneys. The sex difference of UGT expressions in
      rats might be one of the causal factors of the sex difference of the biological
      response to UGT substrates.

PMID- 22863867
TI  - Limited grain growth and chemical ordering during high-temperature sintering of
      PtNiCo nanoparticle aggregates.
AB  - High-temperature sintering of ternary Pt(x)Ni(100-x-y)Co(y) (x = 28-44%, y = 40
      54%) nanoparticles of interest in catalysis was studied in situ and in real-time
      with synchrotron-based x-ray diffraction. For the first time we were able to
      experimentally capture the early stage of the thermal treatment, and found the
      nanoparticles to undergo an unusual two-step coalescence process that involves
      transient growth and restructuring of the nanoparticles. The coalescence process
      is accompanied by lattice contraction, likely due to composition evolution
      towards a random alloy. In the late stage of sintering, evidence was found for
      self-limited grain growth and L1(0) chemical ordering. The order-disorder
      transition temperature was found to be around 800  degrees C in all four ternary
      alloy compositions studied. Fitting of the experimental data with the model for
      grain growth with size-dependent impediment leads to an activation energy for
      mass transport of about 100 kJ mol(-1), and may be used as a predictive tool to
      estimate particle size as a function of heat treatment temperature and duration.

PMID- 22863868
TI  - Plasma microRNA profiles for bladder cancer detection.
AB  - BACKGROUND: Bladder cancer (BC) is a burdensome disease with significant
      morbidity, mortality, and cost. The development of novel plasma-based biomarkers
      for BC diagnosis and surveillance could significantly improve clinical outcomes
      and decrease health expenditures. Plasma miRNAs are promising biomarkers that
      have yet to be rigorously investigated in BC. OBJECTIVE: To determine the
      feasibility and efficacy of detecting BC with plasma miRNA signatures. MATERIALS
      AND METHODS: Plasma miRNA was isolated from 20 patients with bladder cancer and
      18 noncancerous controls. Samples were analyzed with a miRNA array containing
      duplicate probes for each miRNA in the Sanger database. Logistic regression
      modeling was used to optimize diagnostic miRNA signatures to distinguish between
      muscle invasive BC (MIBC), non-muscle-invasive BC (NMIBC) and noncancerous
      controls. RESULTS: Seventy-nine differentially expressed plasma miRNAs (local
      false discovery rate [FDR] <0.5) in patients with or without BC were identified.
      Some diagnostically relevant miRNAs, such as miR-200b, were up-regulated in MIBC
      patients, whereas others, such as miR-92 and miR-33, were inversely correlated
      with advanced clinical stage, supporting the notion that miRNAs released in the
      circulation have a variety of cellular origins. Logistic regression modeling was
      able to predict diagnosis with 89% accuracy for detecting the presence or absence
      of BC, 92% accuracy for distinguishing invasive BC from other cases, 100%
      accuracy for distinguishing MIBC from controls, and 79% accuracy for three-way
      classification between MIBC, NIMBC, and controls. CONCLUSIONS: This study
      provides preliminary data supporting the use of plasma miRNAs as a noninvasive
      means of BC detection. Future studies will be required to further specify the
      optimal plasma miRNA signature, and to apply these signatures to clinical
      scenarios, such as initial BC detection and BC surveillance.

PMID- 22863869
TI  - Low ERCC1 expression is associated with prolonged survival in patients with
      bladder cancer receiving platinum-based neoadjuvant chemotherapy.
AB  - PURPOSE: Excision repair cross-complementation group 1 enzyme (ERCC1) plays a key
      role in the removal of platinum induced DNA adducts and cisplatin resistance.
      Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer
      has not been reported before. We evaluated the prognostic role of ERCC1
      expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.
      MATERIALS AND METHODS: Thirty-eight patients with muscle invasive bladder cancer
      who received neoadjuvant platinum-based chemotherapy were included. Clinical and
      histopathologic parameters along with immunohistochemical ERCC1 staining were
      examined and correlated with response rates and survival. RESULTS: Pathologic
      complete response rates were similar between patients with low and high ERCC1
      expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P =
      0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in
      patients with high ERCC1 expression compared with those with low expression,
      respectively. In multivariate Cox regression analysis: pathological complete
      response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012-0.842, P =
      0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2-11.2, P = 0.019) were
      significantly associated with DFS. Patient age (>60 vs. <= 60 years) (HR 3.4, 95%
      CI 1.2-9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014-0.981, P =
      0.048) and high ERCC expression (HR 6.1, 95 CI 1.9-19.9, P = 0.002) were
      significantly associated with OS. CONCLUSIONS: Our results showed that high ERCC1
      expression was independently associated with shorter disease-free and overall
      survival in patients with bladder cancer who received neoadjuvant platinum-based
      chemotherapy. ERCC1 may represent a potential predictive marker for platinum
      based treatment in bladder cancer.

PMID- 22863871
TI  - Paraaortic lymphatic spread in cervical cancer.

PMID- 22863872
TI  - Rapid molecular detection of pulmonary tuberculosis in HIV-infected patients in
      Santiago, Chile.
AB  - SETTING: Santiago, Chile, has a mean annual tuberculosis (TB) rate of 13 per 100
      000 population; however, TB incidence in human immunodeficiency virus (HIV)
      infected individuals is at least 20 times higher. OBJECTIVE: To assess the
      accuracy of rapid molecular testing for pulmonary  TB (PTB) detection in routine
      care in HIV-infected patients. DESIGN: Cross-sectional study, conducted
      prospectively in five hospitals between March 2010 and June 2011. HIV-positive
      subjects with suspected PTB provided sputum or mouth wash samples that were
      directly processed for acid-fast  smear, mycobacterial cultures and Xpert(r)
      MTB/RIF. Positive test results were reported on the same day. RESULTS: We
      enrolled 166 subjects into the study; 50.6% provided two sputum samples, 33.1%
      only one sputum sample and 16.3% a mouth wash sample. The prevalence of TB was
      8.1% (13/160).  Diagnostic sensitivity increased from 66.7% (95%CI 39.1-86.2) for
      acid-fast smear to 91.7% (95%CI 64.6-98.5) for Xpert MTB/RIF, with comparable
      specificity at 98.6% (146/148, 95%CI 95.2-99.6) and 99.3% (147/148, 95%CI 96.3
      99.9). Xpert MTB/RIF allowed early detection  of rifampicin resistance in 16.6%
      of cases, with rapid adjustment to multidrug-resistant treatment. CONCLUSION:
      Xpert MTB/RIF provided earlier TB diagnosis in 25% more cases than acid-fast
      smear alone. Its implementation should be considered for TB diagnosis in HIV
      positive patients even  outside TB-endemic areas.

PMID- 22863873
TI  - Eastern blotting analysis and isolation of two new dammarane-type saponins from
      American ginseng.
AB  - Ginsenosides, the major active component of American ginseng, were analyzed using
      eastern blotting with anti-ginsenoside Rb(1) and Rg(1) monoclonal antibodies
      (MAbs). Immunoassay-guided fractionation of the methanol extract of American
      ginseng and column chromatography led to the isolation of two new minor dammarane
      type saponins, named quinquenosides Ja (1) and Jb (2). Their structures were
      elucidated to be 6-O-[alpha-L-rhamnopyranosyl(1->2)-beta-D-glucopyranosyl]-20-O
      [beta-D-glucopyranosyl(1->4)-beta-D-glucopyranosyl]-3beta,6alpha,12beta,20beta
      tetrahydroxydammar-24-ene (1) and 3-O-[beta-D-glucopyranosyl(1->2)-beta-D
      glucopyranosyl]-20-O-{[alpha-L-arabinofuranosyl(1->6)-beta-D-glucopyranosyl](1
      >6)-beta-D-glucopyranosyl}-3beta,12beta,20beta-trihydroxydammar-24-ene (2) on the
      basis of chemical and spectroscopic methods.

PMID- 22863876
TI  - Correction of a short cardiac PR interval in a 12-year-old girl with late-onset
      Pompe disease following enzyme replacement therapy.

PMID- 22863877
TI  - Points to consider in the clinical application of genomic sequencing.

PMID- 22863879
TI  - Direct oxygen imaging in titania nanocrystals.
AB  - Recently,  rutile nanotwins were synthesized using high temperature organic
      solvent methods, yielding two kinds of common high-quality rutile twinned
      nanocrystals, (101) and (301) twins, accompanied by minor rutile nanorods (Lu et
      al 2012 CrystEngComm  14 3120-4). In this report, the atomic structures of the
      rutile and anatase nanocrystals are directly resolved with no need for
      calculation or image simulation using atomic resolution STEM techniques. The
      locations of the oxygen rows in the rutile twins' boundaries are directly
      determined from both HAADF images and ABF images. To the best of our knowledge,
      this is the first time oxygen columns have been distinguished in rutile twin
      boundaries using HAADF and BF imaging.

PMID- 22863880
TI  - Linear lichen planopilaris of the face.

PMID- 22863881
TI  - A mouse model to identify cooperating signaling pathways in cancer.
AB  - We here establish a mouse cancer model called Multi-Hit that allows for the
      evaluation of oncogene cooperativities in tumor development. The model is based
      on the stochastic expression of oncogene combinations ('hits') that are mediated
      by Cre in a given tissue. Cells with cooperating hits are positively selected and
      give rise to tumors. We used this approach to evaluate the requirement of Ras
      downstream effector pathways in tumorigenesis.

PMID- 22863882
TI  - Direct observation of mammalian cell growth and size regulation.
AB  - We introduce a microfluidic system for simultaneously measuring single-cell mass
      and cell cycle progression over multiple generations. We use this system to
      obtain over 1,000 h of growth data from mouse lymphoblast and pro-B-cell lymphoid
      cell lines. Cell lineage analysis revealed a decrease in the growth rate
      variability at the G1-S phase transition, which suggests the presence of a growth
      rate threshold for maintaining size homeostasis.

PMID- 22863883
TI  - A high-throughput approach for measuring temporal changes in the interactome.
AB  - Interactomes are often measured using affinity purification-mass spectrometry (AP
      MS) or yeast two-hybrid approaches, but these methods do not provide
      stoichiometric or temporal information. We combine quantitative proteomics and
      size-exclusion chromatography to map 291 coeluting complexes. This method allows
      mapping of an interactome to the same depth and accuracy as AP-MS with less work
      and without overexpression or tagging. The use of triplex labeling enables
      monitoring of interactome rearrangements.

PMID- 22863884
TI  - Age-dependence of relative change in circulating epinephrine and norepinephrine
      concentrations during tilt-induced vasovagal syncope.
AB  - BACKGROUND: Although vasovagal syncope (VVS) is preceded by a surge of
      circulating catecholamines (epinephrine [Epi] and norepinephrine [NE]) of
      adrenal/renal and synaptic origin, prevention of VVS with beta-adrenergic
      blockade has been ineffective except in "older" VVS patients. OBJECTIVE: We
      hypothesized that age-related differences of beta-blocker effect may be due in
      part to differences in the relative magnitudes of Epi and NE release during an
      evolving faint, specifically, greater Epi/NE ratio in younger fainters compared
      to older patients. To assess this hypothesis, we measured changes in Epi/NE
      ratios in younger (<40 years) vs older (>=40 years) patients during head-up tilt
      table test-induced VVS. METHODS: The study comprised 29 patients (12 patients
      >=40 years [mean 56 +/- 10.7 years] and 17 patients <40 years mean 25 +/- 5.7
      years]) with recurrent suspected VVS in whom 70 degrees  head-up tilt testing
      reproduced symptoms. Arterial Epi and NE concentrations were measured at baseline
      (supine), 2 minutes of head-up tilt, and syncope. RESULTS: Baseline Epi and NE
      concentrations and the Epi/NE ratio did not differ in younger and older groups
      (Epi: 90 +/- 65 pg/mL vs 70 +/- 32 pg/mL; NE: 226 +/- 122 pg/mL vs 244 +/- 183
      pg/mL). However, Epi/NE ratio increased to a greater extent in younger fainters
      during head-up tilt and tended to be greater in younger patients at both 2
      minutes (<40: 1.02 +/- 1.29 vs >=40: 0.40 +/- 0.27, P = .11) and at symptoms
      (<40: 2.6 +/- 1.26 vs >=40: 1.6 +/- 0.71, P = .03). At symptoms, Epi/NE ratio
      >=2.5 was observed in 9 of 17 younger patients vs 1 of 12 older patients (P =
      .02). CONCLUSION: Epi/NE ratios tend to be greater in younger fainters, a finding
      that may account in part for the observation that beta-blocker therapy is less
      effective in reducing VVS susceptibility in younger individuals.

PMID- 22863885
TI  - Right superior vena cava drainage into the left atrium revealed by multiples
      strokes after pacemaker implantation.

PMID- 22863886
TI  - Electrical storm after cardiac resynchronization therapy suppressed by triple
      site biventricular pacing and atrioventricular nodal ablation.

PMID- 22863887
TI  - Percutaneous stellate ganglia block for acute control of refractory ventricular
      tachycardia.

PMID- 22863888
TI  - Impact of cigarette minimum price laws on the retail price of cigarettes in the
      USA.
AB  - INTRODUCTION: Cigarette price increases prevent youth initiation, reduce
      cigarette consumption and increase the number of smokers who quit. Cigarette
      minimum price laws (MPLs), which typically require cigarette wholesalers and
      retailers to charge a minimum percentage mark-up for cigarette sales, have been
      identified as an intervention that can potentially increase cigarette prices. 24
      states and the District of Columbia have cigarette MPLs. METHODS: Using data
      extracted from SCANTRACK retail scanner data from the Nielsen company, average
      cigarette prices were calculated for designated market areas in states with and
      without MPLs in three retail channels: grocery stores, drug stores and
      convenience stores. Regression models were estimated using the average cigarette
      pack price in each designated market area and calendar quarter in 2009 as the
      outcome variable. RESULTS: The average difference in cigarette pack prices are 46
      cents in the grocery channel, 29 cents in the drug channel and 13 cents in the
      convenience channel, with prices being lower in states with MPLs for all three
      channels. CONCLUSIONS: The findings that MPLs do not raise cigarette prices could
      be the result of a lack of compliance and enforcement by the state or could be
      attributed to the minimum state mark-up being lower than the free-market mark-up
      for cigarettes. Rather than require a minimum mark-up, which can be nullified by
      promotional incentives and discounts, states and countries could strengthen MPLs
      by setting a simple 'floor price' that is the true minimum price for all
      cigarettes or could prohibit discounts to consumers and retailers.

PMID- 22863889
TI  - In memory of Professor Ralf Pettersson (1945-2011) and Professor Lennart
      Philipson (1929-2011).

PMID- 22863890
TI  - Anisotropic nanoparticles of precise microstructure polyolefins.
AB  - Nanoparticles of precisely branched polyethylenes possess a distinct oblate shape
      resulting from a crystalline lamella in the particle as revealed by SAXS and TEM,
      and display controllable and well-behaved thermal behaviour.

PMID- 22863891
TI  - Fabrication of poly(N-ethylaniline)/lignosulfonate composites and their carbon
      microspheres.
AB  - Novel poly(N-ethylaniline)/lignosulfonate (PNA-LS) composites were prepared via
      an in situ polymerization of N-ethylaniline (NA) with lignosulfonate (LS) as a
      dispersant. Nitrogen-containing carbon materials were obtained by direct
      pyrolysis of the PNA-LS composites at the pyrolytic temperatures ranging from 300
      degrees C to 1200 degrees C. The as-prepared PNA-LS composites and their carbon
      materials were investigated by TGA, SEM, TEM, FTIR and UV-vis spectra, XRD and
      elemental analysis. The results showed that the morphology, structure and
      properties of the PNA-LS composites were depended on the LS:NA mass ratio. PNA-LS
      microspheres with an average diameter of 1300 nm could be fabricated when the
      LS:NA mass ratio was 2.5:97.5, while regular hexagon sheets of PNA-LS composite
      were obtained with the LS:NA mass ratio above 5:95. Furthermore, nitrogen
      containing carbon nanospheres with an average diameter of 820 nm were achieved at
      the carbonization temperature of 800 degrees C.

PMID- 22863893
TI  - Highly-dispersed Ta-oxide catalysts prepared by electrodeposition in a non
      aqueous plating bath for polymer electrolyte fuel cell cathodes.
AB  - The Ta-oxide cathode catalysts were prepared by electrodeposition in a non
      aqueous solution. These catalysts showed excellent catalytic activity and have an
      onset potential of 0.92 V(RHE) for the oxygen reduction reaction (ORR). The
      highly-dispersed Ta species at the nanometer scale on the carbon black was an
      important contributor to the high activity.

PMID- 22863892
TI  - Microbiological characterization in children with aggressive periodontitis.
AB  - The objective of this study was to characterize the subgingival microbiota of
      African-American children with Localized Aggressive Periodontitis (LAP). Fifty
      one children were included. Subgingival plaque samples were taken from diseased
      (DD) and healthy sites (DH) in LAP and from healthy sites in HS and HC and
      analyzed by 16S rRNA-based microarrays. Aggregatibacter actinomycetemcomitans
      (Aa) was the only species found to be both more prevalent (OR = 8.3, p = 0.0025)
      and abundant (p < 0.01) in DD. Filifactor alocis (Fa) was also found to be more
      prevalent in DD (OR 2.31, CI 1.06-5.01, p = 0.03). Most prevalent species in
      healthy sites were Selenomonas spp, Veillonella spp, Streptococcus spp,
      Bergeyella sp, and Kingella oralis. Overall, Streptococcus spp, Campylobacter
      gracilis, Capnocytophaga granulosa, Haemophilus parainfluenzae, and Lautropia
      mirabilis were most abundant in healthy children, while Aa, Fa, Tannerella sp,
      Solobacterium moorei, Parvimonas micra, and Capnocytophaga sp were most abundant
      in LAP. Based on a comprehensive analysis with 16S rRNA-based microarrays, Aa was
      strongly associated and site-specific in LAP. In contrast, other species were
      found to be associated with healthy sites and individuals (ClinicalTrials.gov
      number CT01330719). ABBREVIATIONS: healthy site in healthy sibling (HS); healthy
      site in healthy control child (HC).

PMID- 22863894
TI  - Modeling diffusive Cd and Zn contaminant emissions from soils to surface waters.
AB  - Modeling contaminant transport of diffusive contaminants is generally difficult,
      as most contaminants are located in the top soil where soil properties will vary
      strongly with depth and often a strong gradient in contaminant concentrations
      exists. When groundwater periodically penetrates the contaminated layers,
      stationary models (like most 3D models) cannot adequately describe contaminant
      transport. Therefore we have combined a hydrological instationary model using a
      1D distributed column approach with a simple geochemical model to describe
      contaminant transport in the soil. Special to this model is that it includes
      lateral drainage from the soil column to different types of surface waters, which
      makes it possible to calculate surface water emissions especially for fluctuating
      groundwater tables. To test this model approach, we used it to quantify surface
      water emissions from soils in a catchment in the Kempen area which has been
      diffusively contaminated with Cd and Zn by zinc smelters. We ran the model for
      the period 1880-2000, starting with an uncontaminated soil in 1880. The model
      could describe both water discharge, surface water concentrations and current
      soil contents of Cd and Zn well. Further the model calculations showed that a
      stationary approach would underestimate leaching to surface waters considerably.

PMID- 22863895
TI  - Factors related to postoperative delirium in patients with lower limb ischaemia:
      a prospective cohort study.
AB  - OBJECTIVES: To preoperatively determine candidates at definitive risk of
      postoperative delirium (POD), we identified relevant factors in patients with
      arteriosclerosis obliterans who underwent bypass surgery. DESIGN: A prospective
      cohort study. PATIENTS AND METHODS: 299 patients (age >= 60 years) who underwent
      bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the
      Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used,
      and severity was graded as Grade I-III (mild to severe) based on the Delirium
      Rating Scale. All patients were followed for 3 years. RESULTS: POD occurred in 88
      patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1) days
      postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive
      in 89% and was Grade I, II, and III in 11%, 68%, and 21% respectively. Multiple
      logistic regression analysis identified the following risk factors for POD: age
      >= 72 years (<0.0001), end-stage renal failure (0.001), multiple occlusive
      lesions (<0.0001), cognitive impairment (0.003), and critical limb ischaemia
      (0.034). The 3-year survival rate was similar when comparing POD and non-POD
      patients (84% vs. 88%, NS). CONCLUSIONS: This study identified 5 risk factors for
      POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were
      similar when comparing the patients who experienced POD with those who did not.

PMID- 22863896
TI  - Aortomonoiliac endografting after failed endovascular aneurysm repair:
      indications and long-term results.
AB  - OBJECTIVES: To present long-term results of endoleak/endograft migration
      treatment by aortomonoiliac (AMI) endografting after failed endovascular aneurysm
      repair (EVAR) of infrarenal abdominal aortic aneurysms. DESIGN: Post hoc analysis
      of a prospectively gathered database at a tertiary care university hospital.
      MATERIALS AND METHODS: From March 1995 to November 2010, 23 patients were
      identified who underwent modification into AMI configuration after failed
      elective EVAR. Major causes for modification were type I (with/without endograft
      migration) or type III endoleaks with aneurysm expansion. An average increase in
      aneurysm size of 1.6 cm (range: -1.5 to 10.5 cm) since initial aneurysm treatment
      was observed. Interventional outcomes and long-term results were recorded for
      analysis. RESULTS: Technical success rate of AMI endografting was 95.65% (n =
      22). All except two endoleaks could be successfully sealed with this manoeuvre
      (94.44%). Median time to modification was 5.3 years (interquartile range Q1-Q3:
      1.3-9.3 years). No intra-operative conversion to open surgery was necessary and
      mortality was 0%. Median follow-up was 44 months (interquartile range Q1-Q3: 17
      69 months). CONCLUSIONS: Treatment of graft-related endoleaks/endograft migration
      by AMI endografting after failed EVAR represents a safe and feasible procedure.
      This approach broadens the minimal invasive opportunities of aneurysm treatment,
      and open surgical conversion may be avoided except in selected patients.

PMID- 22863897
TI  - Commentary on 'Aortomonoiliac endografting after failed endovascular aneurysm
      repair: indications and long-term results'.

PMID- 22863899
TI  - The clinical features of hand-arm vibration syndrome in a warm environment--a
      review of the literature.
AB  - The internationally accepted limit values and the health effects of hand
      transmitted vibration exposure have been described extensively in the literature
      from temperate climate countries but not from a tropical climate environment.
      OBJECTIVES: We conducted a systematic review of the health effects of hand
      transmitted vibration exposure in tropical countries to determine the
      characteristics of hand-arm vibration syndrome in a warm environment and compared
      the findings with the results of the systematic reviews published by the US
      NIOSH. METHODS: We searched major medical databases including MEDLINE, PubMed,
      Embase, CINAHL, Ovid and Cochrane based on the terms "hand arm vibration
      syndrome," "hand transmitted vibration," "vibration white finger" and "Raynaud"
      up to January 2011. Only studies conducted in a tropical or subtropical
      environment were selected for the review. The quality of the selected papers was
      assessed independently by two investigators using predefined criteria. A standard
      set of information was abstracted from the papers for review. RESULTS: Only six
      papers from tropical countries and three papers from subtropical countries were
      available in the literature. No vibration white finger was reported in the
      tropical countries. Neurological symptoms were prevalent in the vibration-exposed
      workers. Finger coldness seems to be an important surrogate for vascular disorder
      in a tropical environment. Meta-analysis could not be performed due to inadequacy
      of the information reported in these papers. CONCLUSIONS: The current dose
      response relationship in ISO5349-1 for hand-transmitted vibration exposure is not
      applicable to a tropical environment. Further studies on hand-arm vibration
      syndromes in tropical countries are needed.

PMID- 22863898
TI  - Electrophysiological studies of shoemakers exposed to sub-TLV levels of n-hexane.
AB  - BACKGROUND AND OBJECTIVES: Exposure to n-hexane, a neurotoxic solvent, has been
      associated with sensorimotor polyneuropathy, both in occupationally exposed
      workers and in glue-sniffing addicts. The present study was carried out to
      ascertain whether exposure to sub-TLV levels of n-hexane was associated with
      electrophysiological abnormalities and to determine if these possible
      abnormalities have any correlations with parameters such as the biological
      exposure index (BEI) of this neurotoxic chemical, workers' TWA exposure to n
      hexane and/or duration of employment. MATERIALS AND METHODS: Twenty-seven
      asymptomatic male workers from 6 shoemaking workshops were studied and compared
      with a group of 20 age- and sex-matched normal controls with no history of
      exposure to any neurotoxic agent. They underwent physical examinations as well as
      conventional needle electromyographic examinations and sensory and motor nerve
      conduction studies of upper and lower extremities. The TWA exposure to n-hexane
      and urinary concentration of free 2,5-hexanedione were also determined. Data were
      analyzed using version 16.0 of the SPSS/PC statistical package. RESULTS: The TWA
      exposure to n-hexane was estimated to be 83.2 mg/m(3). Electrophysiological
      studies showed that the amplitudes of sensory nerve action potential (SAP) for
      median and sural nerves were significantly lower in exposed subjects than in
      unexposed normal controls. Additionally, a significant correlation was found
      between these decreases and the urinary concentration of free 2,5-hexanedione.
      CONCLUSION: The significant decrements in SAP amplitudes for the median and sural
      nerves may be considered as appropriate indicators for early detection of n
      hexane-induced peripheral neuropathy in asymptomatic workers with current
      exposure to sub-TLV levels of n-hexane.

PMID- 22863900
TI  - Association of sirolimus adverse effects with m-TOR, p70S6K or Raptor
      polymorphisms in kidney transplant recipients.
AB  - BACKGROUND: The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an
      immunosuppressive drug used in kidney transplantation. m-TOR binds with Raptor
      and phosphorylates p70S6 kinase, a protein involved in numerous cell signalling
      pathways. We examined the association of candidate polymorphisms in m-TOR, Raptor
      and p70S6K, sirolimus dose and exposure, and other time-independent as well as
      time-dependent covariates, with sirolimus-induced adverse events in kidney
      transplant recipients. METHODS: This study included a first group of 113
      patients, switched from a calcineurin inhibitor to sirolimus, and a validation
      group of 66 patients from another clinical trial, with the same immunosuppressive
      regimen. The effects of gene polymorphisms and covariates on the total
      cholesterol, LDL cholesterol, triglycerides, haemoglobin, cutaneous adverse
      events, oedemas and infections were studied using multilinear regression, or
      logistic regression imbedded in linear mixed-effect models. RESULTS: An m-TOR
      variant haplotype was significantly associated with a decrease in haemoglobin
      levels in the two populations of patients (discovery group: beta=-0.82 g/dl,
      P=0.0076; validation group: beta=-1.58 g/dl, P=0.0308). Increased sirolimus
      trough levels were significantly associated with increased total cholesterol
      levels (discovery group: beta=0.02 g/l, P<0.0001; validation group: beta=0.02
      g/l, P=0.0002) and triglyceride levels (discovery group: beta=0.02 g/l, P=0.0059;
      validation group: beta=0.05 g/l, P=0.0370). Sirolimus trough levels were also
      associated with an increased risk for cutaneous adverse events [odds ratio=1.97,
      95% confidence interval (1.32-1.94), P=0.0009] and oedemas [odds ratio=1.16, 95%
      confidence interval (1.03-1.30), P=0.01342] in the discovery group, but this was
      not confirmed in the validation group. CONCLUSION: These results provide evidence
      of an association between an m-TOR haplotype and a decrease in haemoglobin in
      renal transplant recipients.

PMID- 22863901
TI  - A strategy based on galactomannan antigen detection and PCR for invasive
      pulmonary aspergillosis following influenza A (H1N1) pneumonia.

PMID- 22863902
TI  - Isolation of Aspergillus species from the airway of lung transplant recipients is
      associated with excess mortality.
AB  - BACKGROUND: Aspergillus spp. are the leading cause of invasive fungal infection
      in lung transplant recipients. We investigated the relationship between the
      isolation of Aspergillus spp. from the respiratory tract of lung transplant
      recipients and their risk of mortality. METHODS: A retrospective, observational
      cohort study of all patients who received lung allografts between January 1999
      and May 2011 at a single UK centre was performed. The time from transplantation
      to death was analysed using Cox regression models. Isolation of Aspergillus spp.
      from the respiratory tract was included as a covariate in the Cox regression
      model. RESULTS: Two hundred-thirteen patients were included. The median follow-up
      time was 5 years during which 102 patients (47.9%) died. Aspergillus was isolated
      from 74 (34.7%) patients. Twenty patients (27%) had Aspergillus isolated in the
      first 60 days post-transplant. Forty-one patients (55.4%) in the Aspergillus
      group and 61 patients (43.9%) in the non-Aspergillus group died during follow-up.
      A hazard ratio of 2.2 (95% CI 1.5-3.3; P < 0.001) for death following a positive
      Aspergillus sample was observed. CONCLUSION: Isolation of Aspergillus spp. from
      patients following lung transplantation is associated with a significant increase
      in mortality. Novel preventative strategies are required to minimise the impact
      of Aspergillus in lung transplant recipients.

PMID- 22863903
TI  - Increased ophthalmic artery resistance index is associated with cognitive
      impairment in HIV-infected patients.
AB  - OBJECTIVES: Despite the introduction of combined antiretroviral therapy (cART),
      the prevalence of HIV-associated neurocognitive disorders (HANDs) remains high.
      Aim of the study was to investigate the potential relationship between ophthalmic
      artery resistance index (OARI), a marker of subclinical cerebrovascular disease,
      and cognitive performance. METHODS: We performed a cross-sectional cohort study
      by consecutively enrolling HIV-infected patients during routine outpatient
      visits. All subjects underwent a comprehensive neuropsycological battery and
      ultrasonographic assessment of OARI. Patients were classified as cognitively
      impaired if they showed decreased cognitive function involving at least two
      ability domains. OARI was considered abnormal if above 0.72 at left or right
      side. Factors associated with cognitive performance were evaluated by linear and
      logistic regression analysis. RESULTS: A total of 116 patients [78.4% males,
      median age 44 years (IQR 37-49), 13.8% with past AIDS-defining events, median CD4
      482 cells/MUL (IQR 352-690), 79.3% with HIV RNA <20 copies/mL] were enrolled. A
      hundred-thirteen (97.4%) subjects were on cART of which 88.5% on current regimen
      from one year. Fifty-four (46.6%) patients were classified as cognitively
      impaired. ROC curves indicated that the most discriminant left and right OARI
      values for predicting a mild cognitive impairment were >0.72 (AUC = 0.73,
      sensitivity 61.8%, specificity 81.4%, p < 0.001) and >0.71 (AUC = 0.72,
      sensitivity 69.1%, specificity 71.2%, p < 0.001), respectively. Multivariate
      analysis showed that OARI >0.72 (OR 4.7, p = 0.001) was independently associated
      with increased risk of cognitive impairment. Moreover, education (beta = -0.18, p
      = 0.005), Zung depression score (beta = +0.05, p = 0.021) and an abnormal OARI
      (beta = +1.46, p = 0.002) were independently associated with an increased number
      of pathological performances. Evaluating separately each cognitive domain, an
      abnormal OARI confirmed an independent association with lower performance in
      attention and executive functions (p = 0.003) and in psychomotor speed (p =
      0.010). CONCLUSIONS: Increased OARI was associated with lower cognitive
      performance in HIV-infected patients. These findings suggest a potential role of
      subclinical cerebrovascular disease in the pathogenesis of HAND.

PMID- 22863904
TI  - Clinical features of invasive pulmonary aspergillosis vs. colonization in COPD
      patients distributed by gold stage.
AB  - OBJECTIVE: To explore clinical features of invasive pulmonary aspergillosis (IPA)
      vs. colonization among hospitalized COPD patients. METHODS: Records of COPD
      patients with two respiratory cultures yielding Aspergillus were retrospectively
      reviewed. Cases categorized as proven/probable IPA or colonization was analyzed.
      RESULTS: 118 patients were identified: 70 (59.3%) colonized, 48 (40.7%) with IPA
      (42 probable, 6 proven). Higher percentage of IPA patients (vs. colonized)
      presented GOLD III + IV (77.1% vs. 57.1%, p = 0.025). IPA patients presented
      higher Charlson index (3.5 +/- 2.5 vs. 2.6 +/- 2.2, p = 0.027), higher rate of
      ICU admission (27.1% vs. 4.3%, p = 0.001) and worse prognosis (McCabe rapidly
      fatal category: 31.3% vs. 7.1%, p = 0.001). GOLD-I IPA patients presented risk
      factors other than COPD. Before hospitalization, 66.7% IPA and 28.6% colonized
      patients were taking steroids (p < 0.001). Antifungals were administered to 83.3%
      IPA and 21.4% colonized patients (p < 0.001). Mortality was higher among IPA vs.
      colonized patients, both in global (58.3% vs. 10.0%, p < 0.001), GOLD-I (75.0%
      vs. 10.0%, p = 0.041), GOLD-II (42.9% vs. 5.0%, p = 0.042) and GOLD-III patients
      (54.2% vs. 0.0%, p < 0.001), but not in GOLD-IV patients (69.2% vs. 31.3%, p =
      0.066). CONCLUSIONS: IPA should be suspected not only in GOLD-III and GOLD-IV
      COPD patients, with higher mortality in IPA vs. colonized patients for GOLD-II
      and -III COPD patients.

PMID- 22863905
TI  - Anti-infective and osteointegration properties of silicon nitride, poly(ether
      ether ketone), and titanium implants.
AB  - Silicon nitride (Si(3)N(4)) is an industrial ceramic used in spinal fusion and
      maxillofacial reconstruction. Maximizing bone formation and minimizing bacterial
      infection are desirable attributes in orthopedic implants designed to adhere to
      living bone. This study has compared these attributes of Si(3)N(4) implants with
      implants made from two other orthopedic biomaterials, i.e. poly(ether ether
      ketone) (PEEK) and titanium (Ti). Dense implants made of Si(3)N(4), PEEK, or Ti
      were surgically implanted into matching rat calvarial defects. Bacterial
      infection was induced with an injection of 1*10(4)Staphylococcus epidermidis.
      Control animals received saline only. On 3, 7, and 14days, and 3months post
      surgery four rats per time period and material were killed, and calvariae were
      examined to quantify new bone formation and the presence or absence of bacteria.
      Quantitative evaluation of osteointegration to adjacent bone was done by
      measuring the resistance to implant push-out (n=8 rats each for Ti and PEEK, and
      n=16 rats for Si(3)N(4)). Three months after surgery in the absence of bacterial
      injection new bone formation around Si(3)N(4) was ~69%, compared with 24% and 36%
      for PEEK and Ti, respectively. In the presence of bacteria new bone formation for
      Si(3)N(4), Ti, and PEEK was 41%, 26%, and 21%, respectively. Live bacteria were
      identified around PEEK (88%) and Ti (21%) implants, whereas none were present
      adjacent to Si(3)N(4). Push-out strength testing demonstrated statistically
      superior bone growth onto Si(3)N(4) compared with Ti and PEEK. Si(3)N(4)
      bioceramic implants demonstrated superior new bone formation and resistance to
      bacterial infection compared with Ti and PEEK.

PMID- 22863906
TI  - Primary cutaneous gamma delta T-cell lymphoma with brain involvement and
      hemophagocytic syndrome.
AB  - Primary cutaneous gamma delta T-cell lymphoma is a rare diagnosis with only 40
      reported cases. We describe a case of cutaneous gamma delta T-cell lymphoma with
      hemophagocytic syndrome and brain involvement that was not apparent
      morphologically on skin biopsy and was diagnosed as perifolliculitis and lobular
      panniculitis. The biopsy was sent later for molecular studies to the University
      of Washington, which demonstrated a T-cell clone. This case demonstrates that a T
      cell clone may be present in a skin biopsy without morphologic or
      immunophenotypic evidence of lymphoma.

PMID- 22863907
TI  - A reduced graphene oxide based electrochemical biosensor for tyrosine detection.
AB  - In this paper, a 'green' and safe hydrothermal method has been used to reduce
      graphene oxide and produce hemin modified graphene nanosheet (HGN) based
      electrochemical biosensors for the determination of l-tyrosine levels. The as
      fabricated HGN biosensors were characterized by UV-visible absorption spectra,
      fluorescence spectra, Fourier transform infrared spectroscopy (FTIR) spectra and
      thermogravimetric analysis (TGA). The experimental results indicated that hemin
      was successfully immobilized on the reduced graphene oxide nanosheet (rGO)
      through pi-pi interaction. TEM images and EDX results further confirmed the
      attachment of hemin on the rGO nanosheet. Cyclic voltammetry tests were carried
      out for the bare glass carbon electrode (GCE), the rGO electrode (rGO/GCE), and
      the hemin-rGO electrode (HGN/GCE). The HGN/GCE based biosensor exhibits a
      tyrosine detection linear range from 5 * 10(-7) M to 2 * 10(-5) M with a
      detection limitation of 7.5 * 10(-8) M at a signal-to-noise ratio of 3. The
      sensitivity of this biosensor is 133 times higher than that of the bare GCE. In
      comparison with other works, electroactive biosensors are easily fabricated,
      easily controlled and cost-effective. Moreover, the hemin-rGO based biosensors
      demonstrate higher stability, a broader detection linear range and better
      detection sensitivity. Study of the oxidation scheme reveals that the rGO
      enhances the electron transfer between the electrode and the hemin, and the
      existence of hemin groups effectively electrocatalyzes the oxidation of tyrosine.
      This study contributes to a widespread clinical application of nanomaterial based
      biosensor devices with a broader detection linear range, improved stability,
      enhanced sensitivity and reduced costs.

PMID- 22863908
TI  - A homopolymer polymorphism in the TOMM40 gene contributes to cognitive
      performance in aging.
AB  - INTRODUCTION: A highly polymorphic T homopolymer was recently found to be
      associated with late-onset Alzheimer's disease risk and age of onset. OBJECTIVE:
      To explore the effects of the polymorphic polyT tract (rs10524523, referred as
      '523') on cognitive performance in cognitively healthy elderly individuals.
      METHODS: One hundred eighty-one participants were recruited from local
      independent-living retirement communities. Informed consent was obtained, and
      participants completed demographic questionnaires, a conventional paper-and
      pencil neuropsychological battery, and the computerized Cambridge
      Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected
      for determination of the TOMM40 '523' (S, L, VL) and the apolipoprotein E (APOE)
      (E2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were
      eligible for the association analysis. Participants were divided into three
      groups based on '523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized
      linear models were used to evaluate the association between the '523' genotypes
      and neuropsychological test performance. Analyses were adjusted for age, sex,
      education, depression, and APOE E4 status. A planned subanalysis was undertaken
      to evaluate the association between '523' genotypes and test performance in a
      sample restricted to APOE E3 homozygotes. RESULTS: The S homozygotes performed
      better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL
      genotype groups on measures associated with memory (CANTAB Paired Associates
      Learning, Verbal Recognition Memory free recall) and executive function (CANTAB
      measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE E3
      homozygotes only showed that the S/S group performed significantly better than
      the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning
      and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual
      Information Processing latency), and executive function (Digit Symbol
      Substitution). The S/S group performed marginally better than the VL/VL group on
      Intra-Extra Dimensional Set Shift. None of the associations remained significant
      after applying a Bonferroni correction for multiple testing. CONCLUSIONS: Results
      suggest important APOE-independent associations between the TOMM40 '523'
      polymorphism and specific cognitive domains of memory and executive control that
      are preferentially affected in early-stage Alzheimer's disease.

PMID- 22863910
TI  - The Japanese Society of Hypertension Guidelines for Self-monitoring of Blood
      Pressure at Home (Second Edition).

PMID- 22863911
TI  - Feasibility of a cocoon strategy for the prevention of pertussis in Italy:  a
      survey of prevention department healthcare providers.
AB  - A survey was proposed to Italian Prevention Department Directors to investigate
      the opinions on the value of the cocoon strategy and its introduction. Cocoon was
      considered the most efficacious strategy to protect newborns against pertussis by
      76% of the interviewees. Prevention Departments should promote and coordinate
      locally the strategy in 75% of the respondents. Cocoon should be recommended by
      Regional Authority in 82% of the interviewees.

PMID- 22863909
TI  - Homocysteine, progression of ventricular enlargement, and cognitive decline: the
      Second Manifestations of ARTerial disease-Magnetic Resonance study.
AB  - BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline
      and brain atrophy, particularly in older persons. We examined whether
      homocysteine increased the risk for cognitive decline and brain atrophy, and
      evaluated the modifying effect of age. METHODS: Within the Second Manifestations
      of ARTerial disease-Magnetic Resonance study-a prospective cohort study among
      patients with atherosclerotic disease-longitudinal analyses were performed in 663
      patients (mean age: 57 +/- 9 years; follow-up: 3.9 +/- 0.4 years). At baseline
      and follow-up, brain segmentation on magnetic resonance imaging was used to
      quantify relative (%) cortical, ventricular, and global brain volumes, and z
      scores of memory and executive functioning were calculated. Linear regression
      analysis was used to estimate associations of homocysteine (per standard
      deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory,
      and executive functioning at follow-up, adjusted for baseline brain volume,
      memory, and executive functioning, respectively, and age, sex, and vascular risk
      factors. Furthermore, interaction terms between homocysteine and age (continuous)
      were added. RESULTS: Significant interactions were observed between total plasma
      homocysteine (tHcy) and age with cortical, ventricular, and global brain volume
      (for all three measures: P < .05), and between HHCY and age with executive
      functioning (P = .04), and results were stratified by age. In patients aged >=65
      years, increasing tHcy level and HHCY were significantly associated with
      progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]:
      0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a
      decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84,
      95% CI: -1.37 to -0.32, respectively). CONCLUSION: Elevated tHcy was related to
      progression of ventricular enlargement and increased the risk for a decline in
      executive functioning in older persons.

PMID- 22863912
TI  - Serologic analysis of the IgG antibody response in children with varicella zoster
      virus wild-type infection and vaccination.
AB  - INTRODUCTION: In contrast to varicella zoster virus (VZV) primary infection, VZV
      vaccination does not seem to provide lifelong immunity against varicella. Because
      more people get vaccinated every year, the development of sensitive serological
      test systems for the detection of protective anti-VZV IgG will become important
      in the future. METHODS: We have previously developed a novel VZV line assay based
      on 5 different recombinant VZV antigens. In this study, we compared this novel
      assay with a commercially available glycoprotein enzyme immunoassay (RIDASCREEN
      VZV IgG) in detecting anti-VZV IgG of children with previous varicella infection
      and VZV vaccination. RESULTS: One hundred twenty-five children were included in
      this study, 72 with a history of varicella infection and 53 with VZV vaccination.
      Both assays detected anti-VZV IgG antibodies in both study groups with similar
      sensitivities. The VZV line assay revealed striking differences in the anti-VZV
      IgG composition against the VZV open reading frames, 4, 14 and 49, between both
      study groups, indicating that wild-type varicella infection causes a more diverse
      immune response against VZV than does vaccination. The exploitation of these
      results enabled the discrimination of both study groups with a sensitivity of
      0.93 and a specificity of 0.83, indicating that the serologic differentiation of
      children with previous varicella infection and VZV vaccination might be possible.
      CONCLUSION: The VZV line assay enables the detection of anti-VZV IgG with
      sensitivities comparable to glycoprotein enzyme immunoassays and might be
      suitable for the serologic discrimination between children with a history of
      varicella infection and VZV vaccination.

PMID- 22863913
TI  - The cytotoxicity of methylmercury in human microvascular endothelial cells and
      pericytes in culture.
AB  - Methylmercury is an environmental neurotoxin that induces severe neurological
      damage in the brain of humans and animals. The main pathological characteristic
      of methylmercury neurotoxicity is the location of the damage; lesions are
      localized around the deep sulci and fissures in the cerebral cortex, such as the
      calcarine fissure, and the granule cell layer of the cerebellum. Since the
      localization of the damage is suggested to be a result of secondary damage
      occurring due to edematous change in the white cortex, the toxicity of
      methylmercury to cells that compose the microvessels--endothelial cells and
      pericytes--may be important for understanding the neurotoxicity of methylmercury.
      We investigated the toxicity of methylmercury to human brain microvascular
      endothelial cells and pericytes using a cell culture system. It was revealed that
      the toxicity of methylmercury to microvascular cells depends on the cell type and
      density. It is suggested that vascular tissue is one of the targets of
      methylmercury toxicity and that this may contribute to the progression of
      edematous change in the brain. Methylmercury may also be involved in the
      progression of cardiovascular diseases.

PMID- 22863914
TI  - Tamibarotene: a candidate retinoid drug for Alzheimer's disease.
AB  - Tamibarotene (Am80), a synthetic retinoid approved in Japan for treatment of
      acute promyelocytic leukemia (APL), is a retinoic acid receptor (RAR) agonist
      with high specificity for RARalpha and RARbeta over RARgamma. Temporarily and
      spatially specific expression of RARs suggests their pivotal roles in the adult
      brain. Am80 is considered to be a promising candidate drug for treatment of
      Alzheimer's disease (AD) because of its transcriptional controls of multiple
      target genes involved in etiology and pathology of AD. In APP23 AD model mice,
      administration of Am80 decreased the deposition of insoluble amyloid-beta(42). In
      senescence-accelerated mice (SAMP8), Am80 ameliorated the decrease of cortical
      acetylcholine, as well as reducing anxiety in behavioral tests and improving the
      sleep deficit. Am80 also effected a significant improvement of memory in the rat
      scopolamine-induced memory deficit model. Like other retinoids, Am80 also has an
      immunomodulatory effect and reduces secretion of proinflammatory cytokines and
      chemokines by astrocytes and microglia surrounding amyloid-beta plaques. In a rat
      experimental autoimmune encephalomyelitis model, Am80 reduced inflammatory
      cytokines and showed significant efficacy. Retinoids also promote differentiation
      of neural stem cells, and Am80 improved the recovery of spinal cord-injured rats.
      Am80 may also improve vascular factors involved in onset and/or progression of
      AD. Am80 has been in clinical use for treatment of APL in Japan since 2005, and
      has been reported to have fewer side effects than other retinoids. We have
      recently started a clinical study to evaluate the efficacy and safety of Am80 for
      the treatment of Alzheimer's disease.

PMID- 22863915
TI  - New cancer immunotherapy using autologous lymphocytes activated with trastuzumab.
AB  - It is well known that trastuzumab (TTZ) is molecular target drug for breast
      cancer overexpressing human epidermal growth factor receptor 2 (HER2). Novel
      immunotherapy by human peripheral blood mononuclear cells (PBMCs) activated with
      TTZ were examined. Proliferation of lymphocytes after adding of TTZ was obtained.
      Furthermore, lymphocytes activated with TTZ inhibited growth of breast cancer
      cells in vitro. It is noteworthy that remarkably high cellular cytotoxicity in
      lymphocytes activated with TTZ compared with that of CD3- and lymphokine
      (interleukin (IL)2)-activated killer (CD3-LAK) cells commonly used in
      immunotherapy were revealed.

PMID- 22863916
TI  - Anti-atherosclerotic activity of platycodin D derived from roots of Platycodon
      grandiflorum in human endothelial cells.
AB  - This study examined the effects of platycodin D (PD), a triterpene saponin from
      the the root of Platycodon grandiflorum A.DC on human umbilical vein endothelial
      cells (HUVECs) in vitro, which were pre-treated with PD (0.01, 0.15, 0.25 mg/mL),
      respectively, and treated with 50 mg/L oxidized low-density lipoprotein (oxLDL).
      The levels of nitric oxide (NO) and malonaldehyde (MAD) in the culture medium,
      vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion
      molecule-1 (ICAM-1) mRNA expression in endothelium cells and the adhesion of
      monocytes to endothelial cells were measured. The results showed that PD
      increased NO concentration and decreased MDA level induced by oxLDL in the medium
      of endothelial cells. Moreover, PD significantly inhibited the oxLDL-induced
      increase in monocyte adhesion to endothelial cells as well as decreasing mRNA
      expression levels of VCAM-1 and ICAM-1 on these cells. Based on these results, it
      is suggested that PD is a promising anti-atherosclerotic activity, which is at
      least in part the result of its increasing NO concentration, reducing the oxLDL
      induced cell adhesion molecule expression in endothelial cells and the
      endothelial adhesion to monocytes.

PMID- 22863917
TI  - Improvement of atopic dermatitis-like skin lesions by Platycodon grandiflorum
      fermented by Lactobacillus plantarum in NC/Nga mice.
AB  - Atopic dermatitis (AD) is characterized as a multi-factorial inflammatory skin
      disease that has been increasing worldwide. Previously, we demonstrated that FPG,
      which is Platycodon grandiflorum (PG) fermented by Lactobacillus plantarum (LP),
      increases the level of interferon (IFN)-gamma in mouse splenocytes in vitro. In
      this study, we investigated the effects of FPG in an animal model of AD, with a
      particular emphasis on its effects on T helper (Th)1 and Th2 immune responses. To
      assess the potential use of FPG for the inhibition of AD, we established a model
      of AD-like skin lesions in NC/Nga mice. Immunoglobulin isotypes (Igs) and Th1/Th2
      cytokines in the sera and spleens of AD-like mice were examined. In addition,
      histological examination was also performed. AD symptoms in skin lesions improved
      following oral administration of FPG. IgE secretion was significantly down
      regulated, and this was accompanied by decreased levels of interleukin (IL)-4 and
      IgG1 and increased serum levels of IL-12p40 and IgG2a in FPG-treated animals. In
      splenocytes, the production of the Th1 cytokines IL-12p40 and IFN-gamma was up
      regulated, while the levels of the Th2 cytokines IL-4 and 5 were down-regulated
      by FPG treatment. These results suggest that FPG inhibits the development of AD
      like skin lesions in NC/Nga mice by suppressing the Th2 cell response and
      increasing the Th1 cell responses. Our results indicate that FPG is safe and
      effective for the prevention of AD-like skin lesions.

PMID- 22863918
TI  - Panax notoginseng saponins enhances the cytotoxicity of cisplatin via increasing
      gap junction intercellular communication.
AB  - Panax Notoginseng Saponins (PNS) have been well known to have anti-tumor activity
      and enhance cytotoxicity of some cancer chemotherapy agents, but the mechanisms
      underlying these effects are still unknown. This study investigates the effect of
      PNS on cytotoxicity of cisplatin and the relationship between this effect and the
      modulation of gap junctions (GJ) function by PNS in a transfected cell line. The
      cytotoxicity of cisplatin (0.25-1 ug/mL) was increased in the presence of GJ.
      Inhibition of gap junction by either GJ blocker or interception of Connexin (Cx)
      expression decreased the cytotoxicity of cisplatin. Increasing GJ function
      enhanced cytotoxicity of cisplatin, only in the cells with functional GJ. PNS (50
      200 ug/mL) significantly enhanced cisplatin cytotoxicity, but this effect
      required functional gap junctions between the cells. Exposure of the cells to PNS
      (50-200 ug/mL) for 4 h leads to a significant enhance in dye coupling of GJ in a
      dose-dependent manner. These results suggest that PNS increases the cytotoxicity
      of cisplatin through enhancement of GJ activity.

PMID- 22863919
TI  - Effects of fetal exposure to urban particulate matter on the immune system of
      male mouse offspring.
AB  - Urban particulate matter (UPM) has been shown to have an aggravating effect on
      Th2-associated immune systems in adult mice. However, the effects of fetal
      exposure to UPM on immune response in offspring have not been elucidated. In the
      present study, we administered UPM (200 ug/animal) by intratracheal injection to
      pregnant dams on days 7 and 14 of gestation. Subsequently, 9- and 24-week-old
      male offspring were intratracheally injected with ovalbumin (OVA) (four times at
      2-week intervals) to create a mouse model of bronchial asthma. We then evaluated
      the progression of allergic manifestations in the offspring through histological
      findings, the number of inflammatory cells in bronchoalveolar lavage fluid
      (BALF), and protein concentration of cytokines and chemokines in BALF 5, 10, 15,
      and 30 weeks after birth. Histological examination showed that fetal exposure to
      UPM alone caused slight eosinophil and lymphocyte infiltration in the submucosa
      of the airway and bronchial epithelium and significant increases in the number of
      macrophages. Moreover, postnatal intratracheal administration of OVA to offspring
      exposed to UPM in utero caused significant increases in the numbers of
      macrophages, eosinophils, and lymphocytes and in the concentrations of their
      relevant cytokines and chemokines, showing that fetal exposure to UPM aggravated
      the chemically sensitized immune system of male offspring.

PMID- 22863920
TI  - Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor
      activity and dopamine turnover in rats.
AB  - It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4
      dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT),
      and 3-OMD blood level often reaches higher than physiological level in
      Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However,
      the physiological role of 3-OMD has not been well understood. Therefore, in order
      to clarify the effects of 3-OMD on physiological function, we examined the
      behavioral alteration in rats based on locomotor activity, and measured dopamine
      (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic
      administration. The study results showed that repeated administrations of 3-OMD
      increased its blood and the striatum tissue levels in those rats, and decreased
      locomotor activity in a dose dependent manner. Although 3-OMD subchronic
      administration showed no significant change in DA level in the striatum, DA
      metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3
      methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased.
      After 3-OMD washout period (7 d), locomotor activity and DA turnover in those
      rats returned to normal levels. Furthermore, locomotor activity and DA turnover
      decreased by 3-OMD administration were recovered to normal level by acute L-DOPA
      administration. These results suggested that 3-OMD affect to locomotor activity
      via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD
      patients receiving L-DOPA therapy.

PMID- 22863921
TI  - Effects of Leonurine on L-type calcium channel in rat ventricular myocytes.
AB  - Leonurine (Leo) is a special alkaloid principle of Herba leonuri that has
      recently been suggested to improve cardiovascular functions. To date, there is no
      direct ionic evidence of Leo on regulating calcium channels in the heart. In the
      present study, we examined the effects of Leo on action potentials and membrane
      currents recorded from isolated rat ventricular myocytes with the whole-cell
      patch clamp technique. Leo 100 uM shortened the action potential duration in a
      dose-dependent manner. Leo up to 200 uM had no significant effect on the Na+
      current (INa) and K+ current (IK). However, Leo depressed the L-type Ca2+ current
      (ICa,L). In the presence of 20 and 100 uM Leo, the current density was decreased
      and the voltage at half maximal inactivation V0.5 shift to more negative
      potential. The recovery time constant was also delayed. In addition, the
      transcription and protein expression levels of L-type calcium channel (Cav1.2) in
      primary cultured neonatal myocytes from Sprague-Dawley rats were reduced by Leo
      treatment in a dose-dependent fashion as assessed by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot assays. We conclude that Leo
      inhibits L-type calcium channels in cardiomyocytes.

PMID- 22863922
TI  - Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication
      in the human oral squamous carcinoma cell line SAS.
AB  - The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs
      was investigated on the human oral squamous carcinoma cell line SAS. One analog
      induced G2/M phase arrest at 5.3-10.6 uM and induced polyploidy at a higher dose
      (21.2 uM). Importantly, treatment of SAS cells with a combination of the AHL
      analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis
      and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit
      clonogenic survival of SAS cells; however, its radiosensitizing effects were
      relative to not X-irradiation-induced apoptosis but mitotic failure following
      enhanced expression of Aurora A and B. These results suggest that the active AHL
      analog showed growth-suppressive and radiosensitizing effects, which involve
      polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell
      line.

PMID- 22863923
TI  - Peach leaf contains multiflorin a as a potent inhibitor of glucose absorption in
      the small intestine in mice.
AB  - Peach leaf extract has anti-hyperglycemic effects on the postprandial blood
      glucose level in glucose-loaded mice. In our previous study, the mechanism of
      action was considered to be the inhibition of glucose absorption in the small
      intestine. To elucidate the active principle in peach leaf, purification of the
      active compound and a structure determination were performed. With the use of
      bioassay-guided fractionation using glucose-loaded mice, the acetylated
      kaempferol glycoside multiflorin A (MFA), a potent inhibitor of glucose
      absorption from the intestine, was isolated from the MeOH extract of leaf of the
      edible peach Prunus persica. The structure was identified by HPLC using
      thiazolizine derivatives and by an analysis of its spectral data. The inhibitory
      effect of MFA against glucose absorption was demonstrated in the dose dependent
      manner in mice. However, as the deacetylated analog of MFA, multiflorin B did not
      show the activity at the in vivo, the activity of MFA was suggested to depend on
      the acetyl group on the sugar moiety. This is the first report of anti
      hyperglycemic activity of MFA in peach leaf extract. MFA may be useful in
      functional foods or medicines for preventing the postprandial absorption of
      glucose in hyperglycemia.

PMID- 22863924
TI  - Multidrug resistance associated protein 1 together with glutathione plays a
      protective role against 4-hydroxy-2-nonenal-induced oxidative stress in bovine
      aortic endothelial cells.
AB  - 4-Hydroxy-2-nonenal (HNE), an aldehyde produced by lipid peroxidation, induces
      cytotoxicity and oxidative stress. Glutathione (GSH) protects against the
      cytotoxicity of HNE. However, the protective mechanism of GSH has not been fully
      examined. We examined the protective role played by the relationship between GSH
      and multidrug resistance associated protein 1 (MRP1) against the HNE-induced
      oxidative stress in bovine aortic endothelial cells (BAECs). HNE induced the loss
      of viability of BAECs. Exogenous GSH, which is membrane-impermeable, prevented
      the loss of viability induced by HNE by inhibiting HNE uptake in BAECs, probably
      due to the formation of the HNE-SG complex in the extracellular space. We
      demonstrated that HNE induced the expression of MRP1 protein, which can transport
      the HNE-SG complex. The induction of MRP1 protein expression by HNE disappeared
      in BAECs pretreated with L-buthionine sulfoximine, a GSH-depleting agent. This
      result suggests that HNE, together with intracellular GSH, contributes to the
      regulation of MRP1 protein expression. Moreover, we found that MK571, an MRP1
      inhibitor, promoted the HNE-induced oxidative stress and cell death. Taken
      together, these findings suggest that MRP1, together with GSH, plays a protective
      role against the HNE-induced oxidative stress in BAECs.

PMID- 22863925
TI  - Benzofuran derivatives inhibit 11beta-hydroxysteroid dehydrogenase type 1
      activity in rat adipose tissue.
AB  - Excess glucocorticoids promote visceral obesity and insulin resistance. The main
      regulator of intracellular glucocorticoid levels are 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1), which converts inactive glucocorticoid into
      bioactive glucocorticoid such as cortisol in humans and corticosterone in
      rodents; therefore, the inhibition of 11beta-HSD1 has considerable therapeutic
      potential for metabolic diseases including obesity and diabetes. Benzofuran is a
      key structure in many biologically active compounds such as benzbromarone,
      malibatol A and (+)-liphagal. The aim of this study was to investigate the
      inhibitory effect of benzofuran derivatives on 11beta-HSD1 in mesenteric adipose
      tissue from rodents. 11beta-HSD1 activity was determined by incubation of rat
      mesenteric adipose tissue microsomes in the presence of reduced nicotinamide
      adenine dinucleotide phosphate (NADPH) with and without benzofuran derivatives
      (Compounds 1-14). The corticosterone produced was measured by HPLC. More than 40%
      of 11beta-HSD1 inhibition was observed in Compounds 1, 5, 7 and 8. Moreover,
      Compounds 7 and 8 inhibited the 11beta-HSD1 activity in adipose microsomes dose-
      and time-dependently, as well as in 3T3-L1 adipocytes. Compounds 7 and 8 did not
      inhibit 11beta-HSD type 2 (11beta-HSD2), whereas Compounds 1 and 5 inhibited
      11beta-HSD2 by 18.7% and 56.3%, respectively. Further, a kinetic study revealed
      that Compounds 7 and 8 acted as non-competitive inhibitors of 11beta-HSD1. Ki
      (nmol/h/mg protein) values of Compounds 7 and 8 were 17.5 and 24.0, respectively,
      with IC50 (uM) of 10.2 and 25.6, respectively. These data indicate that Compounds
      7 and 8 are convincing candidates for seed compounds as specific inhibitors of
      11beta-HSD1 and have the potential to be developed as anti-obesity drugs.

PMID- 22863926
TI  - Baicalein potently inhibits Rho kinase activity and suppresses actin stress fiber
      formation in angiotensin II-stimulated H9c2 cells.
AB  - Baicalein is a flavonoid (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran4-one) and an
      active principle in Scutellaria baicalensis. The present study was performed to
      investigate the mechanisms underlying the anti-fibrotic effects of baicalein with
      a focus on Rho kinase (ROCK) inhibition. The effect of baicalein on ROCK activity
      was analyzed using an immobilized metal affinity for phosphochemicals (IMAP)
      based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The
      underlying mechanisms of baicalein were examined using angiotensin II-stimulated
      H9c2 cells. Rho kinase (ROCK1 and ROCK2) studies using IMAP-TR-FRET showed that
      baicalein possesses potent ROCK inhibitory activity with IC50 values of 6.55 and
      2.82 uM, respectively. Pretreatment with baicalein (for 2 h) concentration
      dependently decreased the angiotensin II-induced phosphorylation of myosin
      phosphatase (MYPT) and myosin light chain (MLC). Furthermore, baicalein also
      concentration-dependently suppressed actin stress fiber formation in angiotensin
      II-stimulated H9c2 cells. These results suggest that baicalein potently inhibits
      ROCK and that by so doing it modulates actin stress fiber formation. These anti
      fibrotic effects of baicalein explain, at least in part, its pharmacology and
      mode of action.

PMID- 22863927
TI  - Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced neuroinflammation in vitro and in vivo.
AB  - Acacetin (5,7-dihydroxy-4'-methoxyflavone), a constituent of flavone naturally
      present in plants, has anti-cancer and anti-inflammatory activities.
      Neuroinflammation is thought to be one of the major pathological mechanisms
      responsible for Parkinson's disease (PD), and has been a primary target in the
      development of treatment for PD. In the present study, we evaluated the
      neuroprotective effect of acacetin in PD induced by 1-methyl-4-phenylpyridine
      (MPP+)/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined the
      related pathways in vitro and in vivo. In primary mesencephalic culture, acacetin
      protected dopaminergic (DA) cells and inhibited production of inflammatory
      factors such as nitric oxide, prostaglandin E2, and tumor necrosis factor-alpha
      against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the
      effect of acacetin (10 mg/kg/d for 3 d, per os (p.o.)) in a mouse model of PD
      induced by MPTP (30 mg/kg/d for 5 d, intraperitoneally (i.p.)). In the behavioral
      test (pole test), the acacetin-treated mice showed decreased time of turning and
      locomotor activity, which were longer in MPTP-only treated mice. In addition, the
      acacetin-treated group inhibited degeneration of DA neurons and depletion of
      dopamine level induced by MPTP toxicity in the substantia nigra and striatum of
      the brain. Moreover, the acacetin-treated group inhibited microglia activation,
      accompanied by production of inducible nitric oxide synthases and cyclooxygenase
      2. These results suggest that acacetin can protect DA neurons against the
      neurotoxicity involved in PD via its anti-inflammatory action.

PMID- 22863928
TI  - Synthesis and preliminary anticancer evaluation of 10-hydroxycamptothecin
      analogs.
AB  - We have synthesized new 10-hydroxycamptothecin (HCPT) analogs and evaluated their
      anticancer activity in cell culture and in experimental animal tumor model.
      Although the new analogs were less potent against L1210 leukemia cells in vitro,
      some of them were more efficacious against L1210 leukemia in vivo compared to the
      parent HCPT.

PMID- 22863930
TI  - Formulation and evaluation of paclitaxel-loaded polymeric nanoparticles composed
      of polyethylene glycol and polylactic acid block copolymer.
AB  - To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we
      formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG)
      and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical
      properties of PN-PTX prepared were assessed; the mean particle size was around 80
      nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX
      release property was assessed by a dialysis method. Although rapid release of PTX
      was observed just after dosing, around 70% of PTX was stably incorporated in
      polymeric nanoparticles for a long time in the presence of serum. Then, the in
      vivo pharmacokinetics of PN-PTX after intravenous administration was investigated
      in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX
      incorporated exhibited a long blood circulating property, leading to enhanced
      permeability and retention (EPR) effect-driven, time-dependent tumor disposition
      of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake
      clearance of polymeric nanoparticles in the liver and spleen was lower than that
      of PEG liposomes. Since these results indicated that the in vivo disposition
      characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor
      effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any
      significant anti-tumor effect, presumably due to the poor PTX release from
      polymeric nanoparticles. From these results, it is considered that the favorable
      pharmacokinetic properties of nanoparticles and the drug incorporated do not
      always lead to its potent in vivo pharmacological activity, suggesting the
      importance of PTX release properties within tumor tissues.

PMID- 22863929
TI  - Multiple effects of gymnopilin on circulatory system of the rat.
AB  - Gymnopilin is one of the substances produced by the hallucinogenic mushroom,
      Gymnopilus junonius. In this study, we examined effects of gymnopilins purified
      from wild fruiting bodies of G. junonius on contractile activity of aorta
      preparations and blood pressure in rats. Gymnopilins at lower concentrations than
      5 mg/mL did not evoke contraction of helical strips of the thoracic aorta. In
      contrast, gymnopilins (5 mg/mL) applied to the aorta strips pre-contracted by
      norepinephrine (100 nM) caused relaxation. This relaxing action did not depend on
      the activity of the endothelium cells. The relaxing effect of 5-mg/mL gymnopilins
      was observed in aorta strips contracted by angiotensin II (10 nM) and the high K+
      solution (60 mM). Moreover, the adenylyl cyclase inhibitor, SQ-22536,
      significantly inhibited the relaxing effect of gymnopilins at 1 mg/mL on the
      norepinephrine-contracted strips. These results suggested that gymnopilins acted
      directly on smooth muscle cells of the aorta and activated the cAMP-dependent
      cascade to cause the vasodilation. Paradoxically, gymnopilins injection into the
      jugular vein transiently increased blood pressure without affecting the heart
      rate. This result suggests that gymnopilins increase cardiac output and/or
      tension of the artery through the excitation of the vasomotor nerve that overcame
      the direct relaxing effect on the vascular smooth muscle.

PMID- 22863931
TI  - Therapeutic approach to steroid-resistant dermatitis using novel immunomodulator
      FTY720 (Fingolimod) in combination with betamethasone ointment in NC/Nga mice.
AB  - The therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone
      and in combination with betamethasone ointment, was examined in the NC/Nga mouse
      model of spontaneous steroid-resistant dermatitis. Male NC/Nga mice which had
      developed severe dermatitis were divided into six groups: 1) a biweekly
      betamethasone group (betamethasone ointment, twice a week), 2) a daily
      betamethasone group (betamethasone ointment, six times a week), 3) an FTY720
      group (FTY720, orally, three times a week), 4) a biweekly combination group (oral
      FTY720 plus betamethasone ointment, twice a week), 5) a daily combination group
      (oral FTY720 plus betamethasone ointment, six times a week) and 6) a placebo
      group (vehicle alone). The therapeutic efficacy was evaluated in terms of
      severity of dermatitis, epidermal hypertrophy, accumulation and degranulation of
      mast cells and infiltrated CD3+ T cells into the dermis after 4 weeks of
      treatment. Biweekly and daily betamethasone treatments had little effect,
      confirming that the dermatitis was steroid-resistant. In the FTY720 and biweekly
      combination groups, the dermatitis showed no marked improvement. In the daily
      combination group, the dermatitis was significantly (p<0.05, Mann-Whitney U-test)
      improved as compared with the FTY720 group, biweekly and daily betamethasone
      groups and placebo group. Further, epidermal hypertrophy and accumulation of mast
      cells were suppressed. Therefore, combination therapy with FTY720 and daily
      betamethasone ointment is a promising candidate for treatment of steroid
      resistant atopic dermatitis.

PMID- 22863932
TI  - A cell-based, microplate colorimetric screen identifies 7,8-benzoflavone and
      green tea gallate catechins as inhibitors of the hepatitis C virus.
AB  - We describe a cell-based, microplate colorimetric screen for anti-hepatitis C
      virus (HCV) drugs that exploits the HCV-JFH1 viral culture system. Antiviral
      activity was assessed by measuring protection against the HCV-JFH1-induced
      cytopathic effect (CPE) in Huh7.5.1 cells using the 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT) viability assay. The use of serum-free
      medium substantially sensitized Huh7.5.1 cells to HCV-induced CPE, causing
      sufficient cell death to perform colorimetric assays for anti-HCV activity in 96
      well plates. As a proof of concept, we carried out a pilot screen of an inhibitor
      library and identified cyclosporin A and tamoxifen, two compounds with reported
      anti-HCV activity. Using the assay, we discovered the anti-HCV properties of the
      plant flavonoids epigallocatechin gallate (EGCG) and 7,8-benzoflavone (alpha
      naphthoflavone). Other gallate-type catechins and flavones also displayed anti
      HCV activity, but 5,6-benzoflavone (beta-naphthoflavone), flavanone, and non
      gallate catechins were inactive. EGCG apparently acted mainly on HCV entry,
      although it may also block other steps. In contrast, 7,8-benzoflavone was
      presumed to inhibit later stages of the HCV life cycle. This assay is simple,
      reliable and cost-effective; does not require any specially engineered cell lines
      or viruses; and should be useful in the identification of compounds with anti-HCV
      activity.

PMID- 22863933
TI  - Targeting of the Sonic Hedgehog pathway by atractylenolides promotes chondrogenic
      differentiation of mesenchymal stem cells.
AB  - Molecules that enhance chondrogenic differentiation in mesenchymal stem cells
      (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in
      MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which
      promoted Gli1-mediated transcriptional activity, was isolated from an ethyl
      acetate extract of the Rhizoma, Atractylodis macrocephalae. After dehydration,
      atractylenolide III was transformed to atractylenolide I. Both atractylenolides
      were confirmed by MS, UV, IR, 1H- and 13C-NMR spectra. Atractylenolide III (which
      contains -OH at the 8-position) and atractylenolide I (which lacks -OH at the 8
      position) were found to effectively promote the activity of the Gli promoter.
      While the hydroxyl group of atractylenolide III was not essential for the effect
      of atractylenolide, its effect was dependent on Shh signaling. Phenotypic
      cellular analysis indicated that atractylenolides induced MSCs to differentiate
      into chondrocytes, as shown by increased expression of specific chondrogenic
      markers including collagen II, aggrecan and the cartilage related transcription
      factor, Sox9. Atractylenolides significantly increased the expression of Shh and
      its target gene Gli-1, indicating that Shh signaling was activated by
      atractylenolides. Moreover, inhibition of Shh signaling reduced the effect of
      atractylenolides on the chondrogenic phenotype. The discovery that
      atractylenolides induce chondrocytes from MSCs is promising for bony disease
      therapy.

PMID- 22863934
TI  - Intravenous administration of polyethylene glycol-coated (PEGylated) proteins and
      PEGylated adenovirus elicits an anti-PEG immunoglobulin M response.
AB  - A single intravenous administration of polyethylene glycol-coated (PEGylated)
      bovine serum albumin (BSA) and ovalbumin (OVA) elicited an anti-PEG
      immunoglobulin M (IgM) response, similar to that from PEGylated liposomes,
      although the administration did not elicit specific neutralizing antibodies to
      BSA and OVA. A cross-reactivity was observed between anti-PEG IgMs elicited by
      PEG-BSA and PEGylated liposomes. The anti-PEG IgM level induced by PEGylated
      proteins (BSA and OVA) reached the maximum at day 5 following intravenous
      injection. This production pattern was consistent with that induced by PEGylated
      liposomes. Splenectomy suppressed the anti-PEG IgM response against PEG-BSA and
      PEGylated liposomes. These observations relating PEG-BSA and PEGylated liposomes
      indicate that PEGylated proteins might promote the immune responses against PEG
      with a mechanism similar to that of PEGylated liposomes. In addition, a single
      intravenous administration of PEGylated adenovirus (PEG-Ad) also elicited an anti
      PEG IgM response in a PEG-modification ratio dependent manner. To the best of our
      knowledge, this is the first report showing that an intravenous administration
      can elicit an anti-PEG IgM response against PEGylated substances. It appears that
      anti-PEG IgMs can be produced by the systemic administration of a PEGylated
      substance and may limit the efficacy of PEGylated substances such as proteins, Ad
      vector and nanoparticles, due to a cross-reactivity seen in some patients. The
      immunogenicity of PEGylated substances is usually tested against those very
      substances, rather than against covalently attached PEG. Our study suggests that
      the PEG immunogenicity of PEGylated therapeutic agents and particles merits
      further investigation.

PMID- 22863936
TI  - The essential structures of ISP-I that influence serine palmitoyltransferase
      inhibition in Chinese hamster ovary cells.
AB  - We investigated the structure-activity relationship between various ISP-I
      (myriocin, thermozymocidin) analogous which has sphingosine-like structure and
      serine palmitoyltransferase (SPT) in Chinese hamster ovary (CHO) cells utilizing
      sphingolipid production as a marker. Our data suggest that the double bond and/or
      ketone group within the alkyl chain as well as the alkyl chain are necessary for
      ISP-I to inhibit SPT. In addition, a serine structure is necessary for SPT
      inhibitory activity, which confirms previous findings.

PMID- 22863935
TI  - Effect of ethanol pretreatment on skin permeation of drugs.
AB  - It has been demonstrated that ethanol (EtOH) can enhance skin permeation of drugs
      when simultaneously applied with drugs. However, only a few studies have reported
      on the pretreatment effect of EtOH on skin permeations. In this study, the
      pretreatment effects of EtOH on skin permeation of drugs were investigated by
      measuring changes in skin permeation and electrical skin resistance.
      Permeabilities of deuterium oxide (D2O), isosorbide mononitrate (ISMN),
      isosorbide dinitrate (ISDN), calcein sodium (CA-Na), and fluorescein
      isothiocyanate-dextran 4 kDa (FD-4, 3.3-4.4 kDa) were evaluated through Yucatan
      micropig skin pretreated with different concentrations of EtOH solution. From the
      results, almost constant skin permeabilities of D2O and ISDN were observed
      independent of EtOH concentration. Skin permeabilities of ISMN, CA, and FD-4
      increased with low concentrations of EtOH, but decreased with high concentrations
      of EtOH. At 99.5% EtOH pretreatment, skin permeabilities of hydrophilic compounds
      (ISMN, CA, and FD-4) decreased to non-detectable levels. In addition, low
      molecular ion transports were almost constant at any EtOH concentration. Since
      molecular (ion) sizes of ISMN, CA, and FD-4 are larger than Na+, Cl-, and D2O,
      permeation pathway sizes for hydrophilic compounds in the skin barrier may be
      remarkably decreased by pretreatment with high concentrations of EtOH. However,
      the permeability coefficient of ISDN was not influenced by any EtOH
      concentration, since ISDN is a lipophilic, low-molecular compound that permeated
      through the lipophilic stratum corneum pathway. The present results show useful
      information for repeatedly and topically applied formulations containing EtOH,
      and also contribute to the effective use of alcohol formulations.

PMID- 22863937
TI  - Mitochondria take up Ca2+ in two steps dependently on store-operated Ca2+ entry
      in mast cells.
AB  - The ability of mitochondria to take up Ca2+ has important functional implications
      for modulation of cellular Ca2+ signaling. Mitochondrial Ca2+ uptake is
      stimulated by an increase in cytosolic Ca2+ concentration ([Ca2+]c). Here, we
      found that the increase in mitochondrial Ca2+ concentration ([Ca2+]m) occurs in
      two steps in a single antigen-activated mast cell in the presence of
      extracellular Ca2+ (1.0 mM). The two-step elevation of [Ca2+]m was also observed
      after adding thapsigargin, an inhibitor of sarcoplasmic/endoplasmic reticulum
      Ca2+-ATPase. The proportion of mitochondria showing the two-step Ca2+ elevation
      dropped off in direct accord with decrease in extracellular Ca2+ concentration.
      The second step of the [Ca2+]m increase was suppressed significantly in the
      absence of extracellular Ca2+ and in knockdown cells of stromal interaction
      molecule 1 (STIM1), an essential molecule on endoplasmic reticulum (ER) membrane
      for store-operated Ca2+ entry, in the presence of extracellular Ca2+ (1.0 mM),
      while the first elevation was not affected in either case. The results indicate
      that mitochondria take up cytosolic Ca2+ in two steps; first and second uptakes
      are derived from the Ca2+ release from ER and the Ca2+ influx through store
      operated Ca2+ channels, respectively. Additionally, rotenone and antimycin A,
      which are inhibitors of mitochondrial electron transport complex I and III,
      respectively, diminished mitochondrial Ca2+ uptake and significantly suppressed
      degranulation stimulated with antigen. The mitochondrial Ca2+ uptake may modulate
      mast cell function by regulating the [Ca2+]c.

PMID- 22863938
TI  - Anti-proliferative neolignans from Saururus chinensis against human cancer cell
      lines.
AB  - Activity-guided fractionation of an 80% EtOH extract from the aerial parts of
      Saururus chinensis led to isolation of three anti-proliferative neolignans (1-3)
      along with four flavonoids (4-7) and four aristolactams (8-11). Their chemical
      structures were identified by analysis of spectroscopic data. All compounds 1-11
      were evaluated for their activities against 28 human cancer cell lines using an
      in vitro cell proliferation assay. Compounds 1-3 showed potent anti-proliferative
      activities against cervical (C33a, IC50=0.01 uM for 1; 0.28 uM for 2; 2.80 uM for
      3) and lung (NCI-H460, IC50=0.05 uM for 1; 1.37 uM for 2; 6.46 uM for 3) cancer
      cells without any remarkable cytotoxic effects on human normal lung cells as a
      control. Taken together, these data demonstrated the identification of anti
      proliferative neolignans which are active components of S. chinensis.

PMID- 22863939
TI  - Uric acid levels in tissues and plasma of mice during aging.
AB  - Here we quantified the uric acid (UA) levels in 11 tissues and plasma of C57BL/6
      male mice to track its turnover during 3 to 30 months of aging. UA levels in the
      adrenal glands, heart, and spleen increased with aging until 30 months of age.
      Similarly, UA levels in the liver, kidneys, pancreas, and testes increased until
      the mice were 24 months old. UA levels also rose in the lungs and skeletal
      muscles from 3 to 6 months and 6 to 12 months, respectively, and then remained at
      almost the same levels until 30 months of age. In the skin, UA decreased from 3
      to 6 months and then stayed nearly constant until 30 months of age. Moreover, the
      small intestines and plasma had quite stable UA levels during aging. Thus, our
      assessment of 11 tissue types from mice showed that the UA levels increased in
      most tissues during aging.

PMID- 22863940
TI  - In vitro efficacy of continuous mild heat stress on the antifungal susceptibility
      of Candida albicans biofilm formation.
AB  - Elevation in the temperature induces heat stress to both host cells and the
      invading pathogen. This study aimed to determine whether continuous mild heat
      stress (increased temperature without causing significant damage to host cells)
      can increase susceptibility of biofilm formation of the opportunistic fungal
      pathogen Candida albicans to low concentrations of three typical antifungal
      agents. In this way the side effects associated with higher concentrations of the
      antifungal agents on host cells would be reduced. Fluconazole and micafungin at
      concentrations ranging from 0.0625 to 2 ug/mL and amphotericin B at
      concentrations ranging from 0.0625 to 1 ug/mL inhibited less than 20% of cells in
      biofilm formation. Biofilm formation at 39 or 41 degrees C compared to 37 degrees
      C resulted in increased susceptibility to the three agents, but especially
      micafungin. These data suggest that mild heat stress (39 degrees C) would be
      valuable for increasing the effectiveness of low concentrations of antifungal
      agents against C. albicans biofilm formation. Thus, the concept of continuous
      mild heat stress at the site of insertion of medical devices or catheters
      combined with antifungal agents could be beneficial.

PMID- 22863941
TI  - Pinusolide isolated from Biota orientalis inhibits 5-lipoxygenase dependent
      leukotriene C4 generation by blocking c-Jun N-terminal kinase pathway in mast
      cells.
AB  - Pinusolide, an herbal medicine isolated from Biota orientalis L. (B. orientalis),
      inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C4 (LTC4) generation in
      immunoglobulin E (IgE)/Ag-induced bone marrow-derived mast cells (BMMCs) in a
      concentration-dependent manner. To clarify the action mechanism of pinusolide on
      the inhibition of LTC4 generation, we examined the effect of pinusolide on
      phosphorylation of cytosolic phospholipase A2 (cPLA2), as well as translocation
      phospho-cPLA2 and 5-LO to nucleus. Inhibition of LTC4 generation by pinusolide
      was accompanied by a decrease in cPLA2 phosphorylation which occurred via a
      decrease in intracellular Ca2+ influx and blocking the c-Jun N-terminal kinase
      (JNK) pathways. However, pinusolide had no effect on extracellular signal
      regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinas
      phosphorylation. Taken together, the present results suggest that potent
      inhibition of 5-LO dependent LTC4 generation by pinusolide requires both
      suppression of calcium influx and JNK phosphorylation.

PMID- 22863942
TI  - Clionosterol and ethyl cholestan-22-enol isolated from the rhizome of Polygala
      tenuifolia inhibit phosphatidylinositol 3-kinase/Akt pathway.
AB  - Phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors were isolated from the
      rhizome of Polygala tenuifolia WILLD (PT, Polygalaceae), which has been used in
      traditional Chinese medicine for inflammation, dementia, amnesia, neurasthenia
      and cancer, by activity-guided fractionation. For the assay of PI3K/Akt pathway,
      cytoprotective Tat-transduced CHME5 cells, which are the cytoprotective phenotype
      against lypopolysaccharide (LPS)/cycloheximide (CHX), were used. We isolated 4
      anti-cytoprotective compounds, clionasterol (1), ethyl cholestan-22-enol (2), 3-O
      beta-D-glucosyl ethyl cholestan-22-enol (3), and 3-O-beta-D-glucopyranosyl
      clionasterol (4) from EtOAc fraction of PT against Tat-transduced CHME5 cells. Of
      them, (1) and (2) most potently abolished cytoprotective effect of Tat-transduced
      CHME5 cells. These constituents (1) and (2) inhibited the activation of 3
      phosphoinositide-dependent kinase 1 (PDK1) and its downstream molecules,
      Akt/glycogen synthase kinase (GSK)3beta, in PI3K/Akt cell survival signaling
      pathway, but did not suppress the activation of PI3K. Based on these finding, (1)
      and (2) may abolish the cytoprotective phenotype of Tat-transduced CHME5 cells by
      inhibiting PDK1 phosphorylation in PI3K/Akt pathway.

PMID- 22863943
TI  - Direct palladium-catalysed C-H arylation of BODIPY dyes at the 3- and 3,5
      positions.
AB  - A new one-step synthetic method towards 3- and 3,5-arylated BODIPY dyes via
      palladium-catalysed C-H arylation has been developed and its scope has been
      investigated.

PMID- 22863944
TI  - The administration of rescue medication to children with prolonged acute
      convulsive seizures in the community: what happens in practice?
AB  - This paper presents the findings of a review of existing clinical and non
      clinical guidance on the management of children with prolonged acute convulsive
      seizures (PCS) and the administration of rescue medication in community settings.
      Findings are based on desk- and web-based research in 6 countries. Published
      clinical guidelines are mostly limited to the hospital setting and offer few
      explicit recommendations for community settings. Non-clinical guidance on the
      management of medicines at school exists at the national or regional level in all
      6 countries, however rescue epilepsy medication is often not mentioned
      specifically. Existing legal frameworks are vague and open to interpretation. As
      a result, whether a child receives rescue medication at school depends primarily
      on the availability of a willing teacher who accepts responsibility for
      administering it to that child during school hours. Comprehensive guidelines are
      clearly needed that provide practical guidance to ensure that children with PCS
      are treated as quickly as possible in all community settings. Recommendations for
      future action include: providing clearer information on PCS and rescue medication
      to parents and schools; putting in place an individual healthcare plan for every
      child with a history of PCS at his or her school; collecting more empirical data
      to gain a better understanding of the experience of children with PCS at school,
      their parents and teachers; and finally, implementing systematic training for all
      carers of children with PCS. The epilepsy specialist may play an important role
      in ensuring that these recommendations are put into place for their patients.

PMID- 22863945
TI  - Three-drug intra-arterial chemotherapy using simultaneous carboplatin, topotecan
      and melphalan for intraocular retinoblastoma: preliminary results.
AB  - AIMS: To report outcomes with selective intra-arterial chemotherapy (SIAC) using
      simultaneous carboplatin, topotecan, and melphalan for advanced intraocular
      retinoblastoma. METHODS: A retrospective chart review was conducted of patients
      who received three-drug (melphalan, topotecan, and carboplatin) SIAC during 2006
      2011. RESULTS: Twenty-six eyes of 25 patients received the three-drug
      chemotherapy for treatment of advanced retinoblastoma. Reese-Ellsworth group was
      5b in 21 eyes, 5a in 2, 4a in 2, and 3a in 1. Seventeen patients (68%) had
      recurrence after prior intravenous chemotherapy with or without radiotherapy. In
      the three-drug therapy, dose ranges were 2.5-7.5 mg for melphalan, 0.3-0.6 mg for
      topotecan, and 25-50 mg for carboplatin, and median infusions per eye was 2
      (range 1-4). At a mean follow-up of 14 months (range 1-43 months), all patients
      are alive and no patient developed metastatic disease. Twenty-three of 26 eyes
      (88%) survived. Eleven of the 26 eyes (35%) developed recurrent disease and were
      treated with enucleation (n=3) or with focal therapy (n=8) with or without plaque
      brachytherapy (n=3). The Kaplan-Meier estimate of ocular survival at 24 months
      was 75% (95% CI). Electroretinogram showed improvement greater than 25 uV in 4
      eyes (15%), loss greater than 25 uV in 12 eyes (46%), and no change greater than
      25 uV in 10 eyes (39%). CONCLUSIONS: Three-drug SIAC has been used successfully
      to rescue eyes after treatment failure of intravenous chemotherapy and/or single-
      or double-agent SIAC. Twenty-three of 26 eyes avoided both enucleation and
      external beam radiotherapy and retained electroretinogram function.

PMID- 22863946
TI  - Outcomes of deep anterior lamellar keratoplasty in keratoconic eyes with previous
      hydrops.
AB  - AIM: To evaluate outcomes of deep anterior lamellar keratoplasty (DALK) in
      keratoconic eyes with previous hydrops. METHODS: In this retrospective, non
      comparative study, keratoconic eyes with previous hydrops that underwent DALK
      were included. DALK was performed using a modification of Melles's technique of
      optical recognition with pre-Descemet's membrane dissection. Data on preoperative
      and postoperative uncorrected distance visual acuity and best spectacle corrected
      distance visual acuity (BSCVA), postoperative spherical equivalent (SEQ);
      keratometry and adverse events were recorded for all eyes. RESULTS: Ten eyes (10
      patients) underwent DALK in keratoconic eyes with previous hydrops. Mean follow
      up was 56.4 +/- 23.8 months. Preoperatively BSCVA was 6/24 or worse in all eyes.
      At last follow-up, 100% had BSCVA of 6/12 or better. Intraoperative
      microperforation at the site of previous hydrops occurred in six eyes but none
      required conversion to penetrating keratoplasty. At latest follow-up, mean SEQ
      was -2.4 +/- 4.2D, keratometric astigmatism was 3.8 +/- 1.6D and refractive
      astigmatism was 3.4 +/- 2.2D. Mean postoperative keratometry was 43.7 +/- 2.6 and
      central pachymetry 572.6 +/- 65.0 um. CONCLUSIONS: DALK in keratoconic corneas
      with prior hydrops is a safe and effective option that preserves host endothelium
      Intraoperative microperforations at the site of hydrops are common, however with
      good management favourable outcomes are possible.

PMID- 22863947
TI  - Detection of early-stage age related macular degeneration with a compact rarebit
      test.

PMID- 22863948
TI  - Spectral-domain optical coherence tomography in subjects over 60 years of age,
      and its implications for designing clinical trials.
AB  - AIMS: To study the variability of central retinal thickness (CRT), its
      concordance to the fellow eye, and the implications for designing future clinical
      trials using spectral-domain optical coherence tomography (SD-OCT). METHODS:
      Cross-sectional retrospective analysis of European Genetic Database. 632 eyes of
      316 subjects over 60 years of age without macular pathology were examined using
      SD-OCT. RESULTS: Mean CRT was 280.22 um and 281.02 um for the right and left
      eyes, respectively. There was a strong concordance for all measured values
      between right and left eyes. Men had significantly thicker CRT than women.
      Variation up to 23 um difference between both eyes was seen. To detect a change
      of at least 30 um in CRT, a sample size of 90 or 176 per group is needed for a
      single-arm or double-arm study, respectively (alpha=0.05, power=0.80, no loss to
      follow up, assuming SD in future studies=100 um). CONCLUSIONS: Clinical trials
      using CRT as an endpoint are feasible in terms of sample size needed.

PMID- 22863949
TI  - Inhibition of methanogenesis by chlorophenols: a kinetic approach.
AB  - Chlorophenols exert a crucial effect on the methanogenesis, considerably reducing
      both maximum methane potential and methanogenic rates. However, there is not
      enough information about the kinetic mechanism of chlorophenols toxicity on the
      methanogenesis, which is a key aspect for the control of the anaerobic digesters
      because of the sensitivity and the potential for energy recovery derived from
      methane release. The International Water Association-Anaerobic Digestion Model
      No. 1 (IWA-ADM1) can be adapted to a wide range of situations by updating or
      changing the equations in the model. The present study proposes a general kinetic
      model for methanogenesis. This model has been applied to predict the inhibition
      of methanogenesis by chlorophenols, and it can be used for updating the IWA-ADM1
      when treating inhibitory compounds. The model was calibrated and validated using
      a wide broad of experimental sets of data of methane production by granular
      sludge in the presence of 2,4-dichlorophenol (24 DCP), 2,4,6-trichlorophenol
      (246TCP) and pentachlorophenol (PCP) in batch assays. A lag-phase of the effect
      of chlorophenols on the methanogenesis by non-adapted sludge was detected and
      modeled by the kinetic model proposed. In addition, the inhibitory effect of PCP
      was more pronounced on the acetoclastic methanogenesis than on the
      hydrogenotrophic one. Non-competitive and uncompetitive inhibition types were
      detected using 24 DCP and 246 TCP, whereas a suicide or irreversible inhibition
      type was observed in the case of PCP. Values of inhibition constants considerably
      varied depending on the chlorophenol used, between 45 mg24DCPL(-1), 41-51
      mg246TCPL(-1) and 0.9-7.8 mgPCPL(-1). The higher toxicity of PCP is related with
      its hydrophobicity, which was determined by adsorption tests and using partition
      coefficients n-octanol/water. Modeling was accompanied by high statistical
      support in all cases, which confirmed the validation of the model proposed.

PMID- 22863950
TI  - Adolescents' diets do not comply with 2007 Canada's food guide recommendations.
AB  - This study evaluated the eating behaviours of students in grade six and, three
      years later when they were in grade nine, relative to the recommendations of
      Canada's 2007 Food Guide. Students completed a self-administered questionnaire on
      eating behaviours in 2002 (n=647) and again in 2005 (n=520) as part of Better
      Beginnings, Better Futures, a primary prevention initiative among economically
      disadvantaged communities. McNemar analysis and X(2) analysis were used to assess
      differences in compliance with the recommendations of the Food Guide. Differences
      in the mean number of servings of the four food groups and the Other Foods group
      were examined using independent sample t-tests and paired t tests. In grade six,
      5% of males and 7% of females met the minimum number of recommended servings for
      all four food groups. By grade nine this had dropped to 0.4% and 2% respectively.
      Among males who completed the questionnaire in both grade six and grade nine
      there was a decline in the mean number of daily servings for all four food
      groups. For females a similar trend was observed. The likelihood of adolescents
      meeting all Food Guide recommendations decreased from grade six to grade nine.

PMID- 22863951
TI  - Atrophia maculosa varioliformis cutis with histological features of
      perifollicular elastolysis.

PMID- 22863952
TI  - p53 mediates TNF-induced epithelial cell apoptosis in IBD.
AB  - Chronic ulcerative colitis (CUC) is characterized by increased intestinal
      epithelial cell (IEC) apoptosis associated with elevated tumor necrosis factor
      (TNF), inducible nitric oxide synthase (iNOS), and p53. We previously showed that
      p53 is increased in crypt IECs in human colitis and is needed for IEC apoptosis
      in chronic dextran sulfate sodium-colitis. Herein, we examined the roles of TNF
      and iNOS in regulating p53-induced IEC apoptosis in CUC. The IEC TUNEL staining,
      caspases 3, 8, and 9, and p53 protein levels, induced by anti-CD3 monoclonal
      antibody (mAb) activation of T cells, were markedly reduced in TNF receptor 1 and
      2 gene knockout mice. Induction of IEC apoptosis correlated with increased p53,
      which was attenuated in iNOS(-/-) mice. IEC p53 levels and apoptosis were reduced
      in IL-10(-/-) colitic mice treated with neutralizing TNF mAb and the iNOS
      inhibitor, aminoguanidine, further suggesting that TNF and iNOS are upstream of
      p53 during colitis-induced IEC apoptosis. IEC apoptosis and p53 levels were
      assessed in control versus untreated or anti-TNF-treated CUC patients with
      equivalent levels of inflammation. Data indicated that IEC apoptosis and p53
      levels were clearly higher in untreated CUC but markedly reduced in patients
      treated with anti-TNF mAb. Therefore, TNF-induced iNOS activates a p53-dependent
      pathway of IEC apoptosis in CUC. The inhibition of IEC apoptosis may be an
      important mechanism for mucosal healing in anti-TNF-treated CUC patients.

PMID- 22863953
TI  - Glycogen synthase kinase 3beta inhibition prevents monocyte migration across
      brain endothelial cells via Rac1-GTPase suppression and down-regulation of active
      integrin conformation.
AB  - Glycogen synthase kinase (GSK) 3beta has been identified as a regulator of immune
      responses. We demonstrated previously that GSK3beta inhibition in human brain
      microvascular endothelial cells (BMVECs) reduced monocyte adhesion/migration
      across BMVEC monolayers. Herein, we tested the idea that GSK3beta inhibition in
      monocytes can diminish their ability to engage the brain endothelium and migrate
      across the blood-brain barrier. Pretreatment of primary monocytes with GSK3beta
      inhibitors resulted in a decrease in adhesion (60%) and migration (85%), with
      similar results in U937 monocytic cells. Monocyte-BMVEC interactions resulted in
      diminished barrier integrity that was reversed by GSK3beta suppression in
      monocytic cells. Because integrins mediate monocyte rolling/adhesion, we detected
      the active conformational form of very late antigen 4 after stimulation with a
      peptide mimicking monocyte engagement by vascular cell adhesion molecule-1.
      Peptide stimulation resulted in a 14- to 20-fold up-regulation of the active form
      of integrin in monocytes that was suppressed by GSK3beta inhibitors (40% to 60%).
      Because small GTPases, such as Rac1, control leukocyte movement, we measured
      active Rac1 after monocyte activation with relevant stimuli. Stimulation enhanced
      the level of active Rac1 that was diminished by GSK3beta inhibitors. Monocytes
      treated with GSK3beta inhibitors showed increased levels of inhibitory sites of
      the actin-binding protein, cofilin, and vasodilator-stimulated phosphoprotein
      regulating conformational changes of integrins. These results indicate that
      GSK3beta inhibition in monocytes affects active integrin expression, cytoskeleton
      rearrangement, and adhesion via suppression of Rac1-diminishing inflammatory
      leukocyte responses.

PMID- 22863955
TI  - [Treatment of advanced hepatocellular carcinoma].

PMID- 22863956
TI  - [Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma].

PMID- 22863954
TI  - Preeclampsia is associated with alterations in DNA methylation of genes involved
      in collagen metabolism.
AB  - Maternal vascular dysfunction is a hallmark of preeclampsia. A recently described
      vascular phenotype of preeclampsia involves increased expression of matrix
      metalloproteinase-1 (MMP-1) in endothelial cells, vascular smooth muscle, and
      infiltrating neutrophils. In contrast, the expression of tissue inhibitor of
      metalloproteinases-1 (TIMP-1) and collagen type Ialpha 1 is either reduced or not
      changed in the vessels, suggesting an imbalance in vessel collagen degradation
      and synthesis in preeclampsia. In the present study, we explored the possible
      contribution of DNA methylation to the altered expression of genes involved in
      collagen metabolism. We assayed the differences in DNA methylation in omental
      arteries from normal pregnant and preeclamptic women, and determined whether
      reduced DNA methylation increases the expression of MMP-1 in cultured vascular
      smooth muscle cells and a neutrophil-like cell line, HL-60. Several MMP genes,
      including MMP1 and MMP8, were significantly less methylated in preeclamptic
      omental arteries, whereas TIMP and COL genes either were significantly more
      methylated or had no significant change in their DNA methylation status compared
      with normal pregnancy. Experimentally induced DNA hypomethylation increased MMP-1
      expression in cultured vascular smooth muscle cells and MMP-1 cells. Our findings
      suggest that epigenetic regulation contributes to the imbalance in genes involved
      in collagen metabolism in blood vessels of preeclamptic women.

PMID- 22863957
TI  - [Current status and future perspective of sorafenib for advanced hepatocellular
      carcinoma].

PMID- 22863958
TI  - [Development of molecular targeted agents for hepatocellular carcinoma].

PMID- 22863959
TI  - [A case of lymph node metastasis from esophageal small-cell-type endocrine cell
      carcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration].
AB  - A 70-year-old man presented with a 0-IIc lesion in the lower esophagus. He
      underwent esophageal endoscopic submucosal dissection (ESD). The pathological
      diagnosis was squamous cell carcinoma with small cell carcinoma. The patient
      received chemoradiotherapy after ESD, but this was interrupted because of
      myelosuppression. Follow-up endoscopic ultrasonography (EUS) at 5 months after
      the ESD revealed paracardial lymph node swelling (17mm). He underwent EUS-guided
      fine-needle aspiration (FNA), and lymph node metastasis of small-cell-type
      endocrine cell carcinoma was diagnosed. He received VP-16 chemotherapy but died
      22 months after the ESD.

PMID- 22863960
TI  - [A case of gastrointestinal stromal tumor of the stomach mimicking a primary
      tumor of the omentum minus due to the extramural growth].
AB  - We report a case of gastrointestinal stromal tumor (GIST) of the stomach
      mimicking a primary tumor of the omentum minus. The tumor presented as an
      isolated mass in the omentum minus without any adhesion to the stomach.
      Microscopic examination revealed that the tumor pseudocapsule on the gastric side
      included a small smooth muscle tissue component. The patient was given a
      diagnosis of a gastric GIST that showed extensive extramural growth. GISTs should
      not be defined by the localization of the tumor.

PMID- 22863961
TI  - [Acute tumor lysis syndrome in the setting of advanced gastric cancer].
AB  - A 69-year-old man was admitted with right flank pain. The patient was diagnosed
      with advanced gastric cancer with multiple metastases in the liver and abdominal
      lymph nodes and underwent chemotherapy. Three days following the initial
      administration of S-1 plus cisplatin, the patient developed tumor lysis syndrome
      (TLS) with increased LDH, hyperuricemia, hyperkalemia, and elevated creatinine.
      Although rare, TLS following chemotherapy for solid tumors is a potentially fatal
      complication, and high physician awareness is required, especially in patients
      with risk factors, such as bulky disease.

PMID- 22863962
TI  - [A case of duodenal carcinoid tumor accompanied by liver metastasis and lymph
      node metastases in a patient with von Recklinghausen disease].
AB  - We report a case of duodenal carcinoid tumor accompanied by liver metastasis and
      lymph node metastases in a patient with von Recklinghausen disease. A 48-year-old
      woman with von Recklinghausen disease was referred to our hospital because of a
      submucosal tumor at the ampulla of Vater detected by upper gastrointestinal
      endoscopy. The lesion was diagnosed as a carcinoid tumor based on the pathology
      of the biopsy specimen. At operation, although there were liver metastasis on the
      surface of S3 the liver and regional lymph node metastases, we selected
      pancreatoduodenectomy with lymph node dissection and enucleation of the liver
      metastasis. The postoperative course was good and the woman was discharged on
      postoperative day 33. No recurrence has been seen at 24 months since surgery.

PMID- 22863963
TI  - [A case of pseudomembranous colitis concomitant with toxic megacolon and
      paralytic ileus].
AB  - A 60-year-old man was diagnosed as pseudomembranous colitis with chief complaint
      of fever and abdominal distension after a cerebral operation. It was ineffective
      although vancomycin hydrochloride (VCM) was given orally. Complications occurred.
      The patient had toxic megacolon and paralytic ileus. VCM was administrated via an
      ileus tube. In addition, the bowel was lavaged and VCM was sprayed by
      colonoscopy. This therapy was very effective. Generally, a patient with
      pseudomembranous colitis concomitant with toxic megacolon or/and paralytic ileus
      is considered to have a poor prognosis, however, he completely recovered by a
      combination of medical treatment.

PMID- 22863964
TI  - [Successful use of danaparoid in the treatment of portal vein thrombosis that
      developed in a warfarin-administered hepatitis C virus-related cirrhosis
      patient].
AB  - An 84-year-old woman with hepatitis C virus-related cirrhosis, hepatocellular
      carcinoma and atrial fibrillation, who presented with hematemesis, was initially
      treated with endoscopic variceal ligation (EVL) for an esophageal varix
      hemorrhage. However, computed tomography (CT) upon admission had revealed portal
      vein thrombosis, despite having received warfarin for existing atrial
      fibrillation. We subsequently initiated a 2-week treatment with
      danaparoid;warfarin being discontinued in order to reduce the risk of re
      hemorrhage. A follow-up CT after treatment revealed complete reduction of the
      portal vein thrombosis. This is the first successful report of danaparoid use in
      the treatment of portal vein thrombosis that developed in a patient who had
      received warfarin.

PMID- 22863965
TI  - [A case of advanced hepatocellular carcinoma with lung, brain and lymph node
      metastases recurred 8 years after hepatectomy successfully treated by operation,
      radiation and systemic chemotherapy using S-1/CDDP].
AB  - A 30-year-old man underwent a left lobectomy and S5/6 partial hepatectomy in
      August 2001 for hepatocellular carcinoma (HCC). A lung tumor was detected by
      positron emission tomography (PET-CT) 8 years after the surgery. In May 2010, he
      received pulmonary tumor resection and the histopathological findings revealed
      metastasis of HCC. However a metastatic brain tumor was detected by computed
      tomography (CT) in September 2010, therefore surgery and radiation therapy were
      subsequently performed. Thereafter, metastatic hilar lymph node appeared in
      December 2010, therefore we performed systemic chemotherapy using S-1/cisplatin
      combined with radiation therapy for the metastatic tumor. The tumor was markedly
      decreased and no shadow was detected by PET-CT. He has been followed up in the
      outpatient clinic with no recurrence.

PMID- 22863966
TI  - [A case of autoimmune pancreatitis with multifocal mass lesions].
AB  - We present a case of a 73-year-old man with multifocal autoimmune pancreatitis
      (AIP) in the pancreatic head and tail, and who had undergone sigmoidectomy and
      rectectomy 28 months before presenting to our department. Upon presentation, his
      serum IgG4 level was elevated at 267mg/dl, but tumor marker levels were within
      normal ranges. CT and MRI showed two localized pancreatic masses with delayed
      enhancement, but endoscopic retrograde pancreatography revealed neither stenosis
      nor dilatation of the main pancreatic duct. FDG-PET examination showed intense
      uptake in regions concordant with both tumors. The possibility of atypical AIP
      was a concern, but malignant tumor could not be clinically or radiologically
      excluded. Endoscopic ultrasonographic fine-needle aspiration biopsy was
      performed, but no malignant cells were detected. The patient underwent subsequent
      distal pancreatectomy. Histological evaluation of the tumors showed the presence
      of many IgG4-positive plasma cells without any evidence of malignancy.

PMID- 22863967
TI  - Bioaccumulation of tritiated water in phytoplankton and trophic transfer of
      organically bound tritium to the blue mussel, Mytilus edulis.
AB  - Large releases of tritium are currently permitted in coastal areas due to
      assumptions that it rapidly disperses in the water and has a low toxicity due to
      its low energy emissions. This paper presents a laboratory experiment developed
      to identify previously untested scenarios where tritium may concentrate or
      transfer in biota relevant to Baltic coastal communities. Phytoplankton
      populations of Dunaliella tertiolecta and Nodularia spumigena were exposed at
      different growth-stages, to tritiated water (HTO; 10 MBq l(-1)). Tritiated D.
      tertiolecta was then fed to mussels, Mytilus edulis, regularly over a period of
      three weeks. Activity concentrations of phytoplankton and various tissues from
      the mussel were determined. Both phytoplankton species transformed HTO into
      organically-bound tritium (OBT) in their tissues. D. tertiolecta accumulated
      significantly more tritium when allowed to grow exponentially in HTO than if it
      had already reached the stationary growth phase; both treatments accumulated
      significantly more than the corresponding treatments of N. spumigena. No effect
      of growth phase on bioaccumulation of tritium was detectable in N. spumigena
      following exposure. After mussels were given 3 feeds of tritiated D. tertiolecta,
      significant levels of tritium were detected in the tissues. Incorporation into
      most mussel tissues appeared to follow a linear relationship with number of
      tritiated phytoplankton feeds with no equilibrium, highlighting the potential for
      biomagnification. Different rates of incorporation in species from a similar
      functional group highlight the difficulties in using a 'representative' species
      for modelling the transfer and impact of tritium. Accumulations of organic
      tritium into the mussel tissues from tritiated-phytoplankton demonstrate an
      environmentally relevant transfer pathway of tritium even when water
      concentrations are reduced, adding weight to the assertion that organically bound
      tritium acts as a persistent organic pollutant. The persistence, potential for
      biomagnification and the increased toxicity of organic tritium increases the
      potential impact on the environment following a release of HTO; current
      legislation does not adequately take into account the nature of organic forms of
      tritium and therefore may be underestimating accumulation and toxic effect of
      tritium in the environment. Such information is necessary to accurately assess
      the distribution of tritium following routine releases, and to adequately protect
      the environment and humans.

PMID- 22863968
TI  - Association of STXBP4/COX11 rs6504950 (G>A) polymorphism with breast cancer risk:
      evidence from 17,960 cases and 22,713 controls.
AB  - BACKGROUND AND AIMS: Epidemiological studies have investigated the association
      between STXBP4/COX11 rs6504950 (G>A) polymorphism and breast cancer
      susceptibility. However, the results are still controversial. Hence, we conducted
      a meta-analysis of the STXBP4/COX11 polymorphism and risk of breast cancer to
      obtain the most reliable estimate of the association. METHODS: PubMed, Embase and
      Web of Science databases were searched. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were extracted and pooled to assess the strength of
      the association between STXBP4/COX11 rs6504950 (G>A) polymorphism with breast
      cancer risk. RESULTS: A total of four eligible studies including 17,960 cases and
      22,713 controls based on the search criteria were involved in this meta-analysis.
      The distributions of genotypes in the controls were all in agreement with Hardy
      Weinberg equilibrium. We observed that STXBP4/COX11 rs6504950 polymorphism was
      significantly correlated with breast cancer risk when all studies were pooled
      into the meta-analysis (the allele contrast model: OR = 0.93, 95% CI = 0.87-0.99;
      the heterozygote codominant model: OR = 0.87, 95% CI = 0.83-0.90; the dominant
      model OR = 0.92, 95% CI = 0.88-0.96). CONCLUSION: This meta-analysis indicated
      that the rs6504950 AA/AG genotypes are associated with a significantly decreased
      risk of breast carcinogenesis.

PMID- 22863969
TI  - Fomitoside-K from Fomitopsis nigra induces apoptosis of human oral squamous cell
      carcinomas (YD-10B) via mitochondrial signaling pathway.
AB  - In this study, a new lanostane triterpene glycoside (fomitoside-K) having
      biologically active molecules was isolated from a mushroom Fomitopsis nigra to
      test its anticancer activity on human oral squamous cell carcinomas (YD-10B). We
      focused on the effect of fomitoside-K on apoptosis, the mitochondria-mediated
      death pathway and the accumulation of reactive oxygen species (ROS) in YD-10B
      cells. Fomitoside-K could induce a dose and time-dependent apoptosis in YD-10B
      cells as characterized by cell morphology, cell cycle arrest, inhibition of
      survivin, activation of poly(ADP-ribose) polymerase (PARP), caspase-3, -9 and an
      increased expression ratio of Bax/Bcl-2. The mitochondria membrane potential loss
      and cytochrome c (Cyt C) release from mitochondria to cytosol were observed
      during the induction. Moreover, fomitoside-K caused dose-dependent elevation of
      intracellular ROS level and increase phosphorylation of c-Jun N-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK) in YD-10B cells. To further
      investigate the mechanisms, we examined the effects of ROS scavenger N-acetyl-L
      cysteine (NAC) and selective inhibitors for mitogen activated protein kinase
      (MAPK) pathways on the cell death. The fomitoside-K induced cell death by ROS was
      significantly inhibited by NAC, ERK (PD98059) and JNK inhibitor (SP600125). In
      addition, fomitoside-K has a synergistic effect with adriamycin in suppressing
      the growth of YD-10B cells. These data suggest that fomitoside-K induces
      apoptosis in YD-10B cells through the ROS-dependent mitochondrial dysfunction
      pathway and provides a mechanistic framework for further exploring the use of
      fomitoside-K against the proliferation of human oral cancer.

PMID- 22863971
TI  - Granulosa cells in the uterosacral ligament: case report and review of the
      literature.
AB  - Granulosa cells are components of the sex cord-stromal cells in the ovary
      responsible for steroidogenesis. Uncommonly, extraovarian granulosa cells have
      been reported to be associated with malignant processes of the ovary. We report a
      unique case of benign granulosa cells, found during routine laparoscopic
      evaluation, in the uterosacral ligaments in a 20-year-old patient with chronic
      pelvic pain and infertility. Possible mechanisms include implantation of released
      granulosa cells from a normal ovary or arising from a focus of mullerianosis. Of
      note, a focus of endosalpingiosis and endometriosis was also identified within
      the specimen.

PMID- 22863970
TI  - Acute syphilitic posterior placoid chorioretinitis: report of a case series and
      comprehensive review of the literature.
AB  - PURPOSE: To describe the clinical and angiographic features of a series of
      patients with acute syphilitic posterior placoid chorioretinitis (ASPPC) in the
      context of previously published cases. METHODS: A retrospective, noncomparative,
      multicenter chart review was performed on 16 patients with active ASPPC. Positive
      serologic tests supported the diagnosis in all patients. Color and red-free
      photographs as well as fluorescein angiography were obtained in each case.
      Indocyanine green angiography, optical coherence tomography, and fundus
      autofluorescence were performed on selected patients. A total of 44 previously
      published cases of ASPPC were identified using both a Medline Search and
      references listed in articles identified. RESULTS: Ocular involvement was
      bilateral in 9 of our 16 patients (56.3%). The mean and median ages at
      presentation were 40 and 38 years, respectively (range 28-57 years). Nine
      patients (56.3%) were human immunodeficiency virus positive, with most recent CD4
      cell counts ranging from 160 cells/MUL to 450 cells/MUL and a median CD4 cell
      count of 250 cells/MUL. Seven of 16 patients (43.8%) had a history of
      mucocutaneous manifestations of secondary syphilis, whereas 4 (25.0%) had
      evidence of neurosyphilis. Anterior chamber and/or vitreous inflammation was
      evident in 13 patients (81.3%). Fifteen of 16 patients had positive venereal
      disease research laboratory or rapid plasma regain titers, and 13 of 13 tested
      patients had a positive serum fluorescent treponemal antibody absorption. The
      initial vision in the 25 affected eyes ranged from 20/20 to counting fingers,
      with a median of 20/80. In all patients, posterior segment examination in the
      involved eyes revealed a large, yellowish, placoid, outer retinal lesion.
      Fluorescein angiography showed progressive hyperfluorescence in the area of the
      lesion, often with scattered focal hypofluorescence, or leopard spotting.
      Inflammation subsided, the yellowish lesions resolved, and vision improved
      shortly after antibiotic therapy in 20 of 25 affected eyes. Visual acuity at last
      visit ranged from 20/20 to 20/150, with a median final vision of 20/25. A review
      of the literature revealed 44 previously reported cases of ASPPC. Shared
      demographic, clinical, and angiographic features were summarized. CONCLUSION:
      Acute syphilitic posterior placoid chorioretinitis is an uncommon but clinically
      and angiographically distinct manifestation of ocular syphilis. All patients with
      characteristic clinical and angiographic findings of ASPPC should be tested for
      both neurosyphilis and human immunodeficiency virus coinfection. Vision recovery
      typically followed completion of appropriate antibiotic therapy.

PMID- 22863972
TI  - Diagnosis and management of endometrial hyperplasia.
AB  - Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic
      diagnosis and a known precursor of endometrial carcinoma, the most common
      gynecologic malignancy. During the reproductive years, the risk of EH is
      increased by conditions associated with intermittent or absent ovulation, in
      particular, polycystic ovary syndrome. After menopause when ovulation has ceased,
      EH is more common in women with conditions that increase levels of circulating
      estrogen such as obesity or estrogen replacement therapy. Women with EH are at
      increased risk for both concurrent and subsequent endometrial cancer. The risk of
      coexisting cancer in women with a diagnosis of EH at endometrial sampling is due
      to limitations in both endometrial sampling and the diagnostic reproducibility
      among pathologists. These diagnostic uncertainties add to the complexity of
      managing EH. This review offers a rational approach to prevention, diagnosis, and
      treatment of EH, including hormone therapy and conservative surgical methods.

PMID- 22863974
TI  - Direct exfoliation of graphite with a porphyrin--creating functionalizable
      nanographene hybrids.
AB  - Exfoliation of graphite was achieved using a free-base porphyrin 1 resulting in
      an efficient fabrication of single-layer nanographene (NG)- hybrid platelets that
      can be further functionalized with other nanomaterials. The novel nanographene
      porphyrin hybrids reveal efficient charge transfer in the excited state.

PMID- 22863973
TI  - Valproic acid shows a potent antitumor effect with alteration of DNA methylation
      in neuroblastoma.
AB  - Epigenetic aberrations and a CpG island methylator phenotype are associated with
      poor outcome in children with neuroblastoma (NB). Previously, we have shown that
      valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, exerts antitumor
      effects in an NB xenograft model. However, the underlying antitumor molecular
      mechanisms are largely unknown. In this study, we examined the role of HDAC in
      cell proliferation, cell cycle progression, gene expression patterns, and
      epigenome in NB. Cell proliferation, cell cycle progression, caspase activity,
      RNA and protein expression, quantitative methylation, and global DNA methylation
      were examined in NBL-W-N and LA1-55n NB cell lines. Our studies showed that
      inhibition of HDAC decreased NB proliferation, and induced caspase activity and
      G1 growth arrest. Expression patterns of cancer-related genes were modulated by
      VPA. The expression of THBS1, CASP8, SPARC, CDKN1A, HIC1, CDKN1B, and HIN1 was
      upregulated, and that of MYCN and TIG1 was downregulated. HDAC inhibition
      decreased methylation levels of THBS1 and RASSF1A promoters. Inhibition of HDAC
      increased acetylation of histone 4 and overall DNA methylation levels. Our
      studies showed that inhibition of HDAC blocked cell proliferation and cell cycle
      progression in relation to alteration in cancer-related genes, increased overall
      DNA methylation, and decreased methylation of tumor suppressor genes. Further
      studies examining the antitumor effects of VPA in NB are warranted.

PMID- 22863975
TI  - Electrical-field-induced structural change and charge transfer of lanthanide
      salophen complexes assembled on carbon nanotube field effect transistor devices.
AB  - The application of a negative gate voltage on a carbon nanotube field effect
      transistor decorated by a binuclear Tb(III) complex leads to the generation of a
      negatively charged mononuclear one, presenting an electron density transfer to
      the nanotube and ambipolar behaviour.

PMID- 22863977
TI  - Idiopathic dysesthesia, complex regional pain syndrome and video-thermography: a
      new tool for diagnosis?

PMID- 22863976
TI  - Evaluation of the deformation and corresponding dosimetric implications in
      prostate cancer treatment.
AB  - The cone-beam computed tomography (CBCT) imaging modality is an integral
      component of image-guided adaptive radiation therapy (IGART), which uses patient
      specific dynamic/temporal information for potential treatment plan modification.
      In this study, an offline process for the integral component IGART framework has
      been implemented that consists of deformable image registration (DIR) and its
      validation, dose reconstruction, dose accumulation and dose verification. This
      study compares the differences between planned and estimated delivered doses
      under an IGART framework of five patients undergoing prostate cancer radiation
      therapy. The dose calculation accuracy on CBCT was verified by measurements made
      in a Rando pelvic phantom. The accuracy of DIR on patient image sets was
      evaluated in three ways: landmark matching with fiducial markers, visual image
      evaluation and unbalanced energy (UE); UE has been previously demonstrated to be
      a feasible method for the validation of DIR accuracy at a voxel level. The dose
      calculated on each CBCT image set was reconstructed and accumulated over all
      fractions to reflect the 'actual dose' delivered to the patient. The deformably
      accumulated (delivered) plans were then compared to the original (static) plans
      to evaluate tumor and normal tissue dose discrepancies. The results support the
      utility of adaptive planning, which can be used to fully elucidate the dosimetric
      impact based on the simulated delivered dose to achieve the desired tumor control
      and normal tissue sparing, which may be of particular importance in the context
      of hypofractionated radiotherapy regimens.

PMID- 22863978
TI  - Tentorial dural arteriovenous fistula presenting as episodic weakness mimicking
      periodic paralysis.
AB  - We report a rare case of episodic limb weakness caused by a tentorial dural
      arteriovenous fistula (DAVF) draining into the perimesencephalic veins. A middle
      aged man presented with episodes of transient quadriparesis preceded by recurrent
      vomiting. The patient was initially suspected of having periodic paralysis but,
      due to the presence of recurrent vomiting and brisk reflexes, MR imaging of the
      brain was performed which revealed marked T2 hyperintensity of the brainstem and
      cervical cord along with multiple prominent flow voids. Cerebral angiography
      showed a Borden type 3 DAVF at the left tentorial margin which was draining into
      the perimesencepahlic and perimedullary veins and refluxing into the cervical
      epidural veins. The patient made a remarkable recovery after surgical
      interruption of the fistula. 

PMID- 22863979
TI  - Obesity and intracranial in-stent thrombosis.
AB  - A morbidly obese, diabetic, hypertensive patient, with severe intracranial left
      middle cerebral artery (MCA) stenosis, suffered recurrent stereotyped transient
      ischemic attacks over 2 months, despite taking daily antiplatelet agents, high
      dose statin, insulin and an angiotensin converting enzyme inhibitor. A left MCA
      (M1) Wingspan stent-assisted angioplasty was performed after standard loading,
      and daily doses of clopidogrel were given 3 days prior to the procedure.
      Immediately after the procedure, the patient developed a left hemispheric
      ischemic stroke syndrome. Urgent re-angiography identified an acute intracranial
      in-stent thrombosis. This complication was immediately treated successfully with
      abciximab and balloon angioplasty. The patient had persistent residual stroke
      despite complete recanalization of the thrombosed stent within 3 h of occlusion.
      The patient was subsequently found to have incomplete inhibition of platelet
      activity despite being on clopidogrel 150 mg and aspirin 81 mg daily and having a
      normal CYP-2C19 genotype, suggesting that suboptimal antiplatelet inhibition,
      secondary to morbid obesity, contributed to his in-stent thrombosis. Obese
      patients undergoing coronary artery stenting routinely receive larger loading and
      maintenance doses of clopidogrel. Our case suggests that obese patients
      undergoing intracranial stenting may also benefit from higher than conventional
      clopidogrel doses prior to intracranial stenting, to decrease risk of acute in
      stent occlusion. 

PMID- 22863980
TI  - Venous sinus stenting for idiopathic intracranial hypertension: a review of the
      literature.
AB  - Idiopathic intracranial hypertension (IIH) is characterized by headache,
      papilledema, visual field changes and tinnitus with elevated cerebral spinal
      fluid opening pressures on lumbar puncture. Left untreated, this condition can
      lead to permanent visual loss. Previous treatment modalities include medical
      management, therapeutic lumbar puncture and optic nerve sheath fenestration. They
      have proved to be effective but carry high rates of symptom recurrence or
      procedural complications. Focal dural venous sinus stenoses have been identified
      in many patients with IIH, leading to development of treatment through venous
      sinus angioplasty and stenting. A review of the literature was performed which
      identified patients with IIH treated with venous sinus stenting. The procedural
      data and outcomes are presented. A total of 143 patients with IIH (87% women,
      mean age 41.4 years, mean body mass index 31.6 kg/m(2)) treated with venous sinus
      stenting were included in the analysis. Symptoms at initial presentation included
      headache (90%), papilledema (89%), visual changes (62%) and pulsatile tinnitus
      (48%). There was a technical success rate of 99% for the stent placement
      procedure with a total of nine complications (6%). At follow-up (mean 22.3
      months), 88% of patients experienced improvement in headache, 97% demonstrated
      improvement or resolution of papilledema, 87% experienced improvement or
      resolution of visual symptoms and 93% had resolution of pulsatile tinnitus. In
      patients with IIH with focal venous sinus stenosis, endovascular stent placement
      across the stenotic sinus region represents an effective treatment strategy with
      a high technical success rate and decreased rate of complications compared with
      treatment modalities currently used. 

PMID- 22863982
TI  - Comparison of Enterococcus quantitative polymerase chain reaction analysis
      results from fresh and marine waters on two real-time instruments.
AB  - The U.S. Environmental Protection Agency will be recommending a quantitative
      polymerase chain reaction (qPCR) method targeting Enterococcus spp. as an option
      for monitoring recreational beach water quality. A practical consideration for
      implementation of this and other qPCR methods is whether the results are
      comparable on different PCR instruments. In this study, quantitative estimates of
      Enterococcus densities from marine and freshwater samples were determined by the
      qPCR method from cycle threshold (Ct) measurements obtained on Applied Biosystems
      StepOnePlus and Cepheid SmartCycler instruments. Three variations of a
      comparative Ct model, differing in their sources of calibration data, were used
      in the estimations. Both traditional and Bayesian statistical modeling approaches
      were examined in the instrument comparisons. The traditional analysis of variance
      (ANOVA) approach indicated no significant differences (p>0.05) between mean
      density estimates from the instruments in two of the three model variations. The
      Bayesian approach indicated that the 95% Bayesian credible intervals of density
      estimates from the instruments overlapped in all models; however, the uncertainty
      of the estimates varied depending on the model. These results support the
      interchangeable use of the two instruments in the method and also illustrate the
      importance of defining the source of calibration data used in the comparative Ct
      model.

PMID- 22863983
TI  - Amperometric determination of total phenolic content in wine by laccase
      immobilized onto silver nanoparticles/zinc oxide nanoparticles modified gold
      electrode.
AB  - A method is described for construction of a highly sensitive amperometric
      biosensor for measurement of total phenolic compounds in wine by immobilizing
      laccase covalently onto nanocomposite of silver nanoparticles (AgNPs)/zinc oxide
      nanoparticles (ZnONPs) electrochemically deposited onto gold (Au) electrode.
      Scanning electron microscopy, X-ray diffraction, and electrochemical impedance
      spectroscopy were applied for characterization of the surface morphology of the
      modified electrode, and cyclic voltammetry was used to investigate the
      electrochemical properties of the proposed electrode toward the oxidation of
      guaiacol. The linearity between the oxidation current and the guaiacol
      concentration was obtained in a range of 0.1 to 500MUM with a detection limit of
      0.05MUM (signal-to-noise ratio (S/N)=3) and sensitivity of 0.71MUAMUM(-1)cm(-2).
      The electrode showed increased oxidation and reduced reduction current with the
      deposition of AgNPs/ZnONPs on it. R(CT) values of ZnONPs/Au, AgNPs/ZnONPs/Au, and
      laccase/AgNPs/ZnONPs/Au electrode were 220, 175, and 380Omega, respectively. The
      biosensor showed an optimal response within 8s at pH 6.0 (0.1M acetate buffer)
      and 35 degrees C when operated at 0.22V against Ag/AgCl. Analytical recovery of
      added guaiacol was 98%. The method showed a good correlation (r=0.99) with the
      standard spectrophotometric method, with the regression equation being y=1.0053x
      3.5541. The biosensor lost 25% of its initial activity after 200 uses over
      5months.

PMID- 22863981
TI  - Targeting the intragraft microenvironment and the development of chronic
      allograft rejection.
AB  - In this review, we discuss a paradigm whereby changes in the intragraft
      microenvironment promote or sustain the development of chronic allograft
      rejection. A key feature of this model involves the microvasculature including
      (a) endothelial cell (EC) destruction, and (b) EC proliferation, both of which
      result from alloimmune leukocyte- and/or alloantibody-induced responses. These
      changes in the microvasculature likely create abnormal blood flow patterns and
      thus promote local tissue hypoxia. Another feature of the chronic rejection
      microenvironment involves the overexpression of vascular endothelial growth
      factor (VEGF). VEGF stimulates EC activation and proliferation and it has
      potential to sustain inflammation via direct interactions with leukocytes. In
      this manner, VEGF may promote ongoing tissue injury. Finally, we review how these
      events can be targeted therapeutically using mTOR inhibitors. EC activation and
      proliferation as well as VEGF-VEGFR interactions require PI-3K/Akt/mTOR
      intracellular signaling. Thus, agents that inhibit this signaling pathway within
      the graft may also target the progression of chronic rejection and thus promote
      long-term graft survival.

PMID- 22863984
TI  - Longitudinal impact of frequent geographic relocation from adolescence to
      adulthood on psychosocial stress and vital exhaustion at ages 32 and 42 years:
      the Amsterdam growth and health longitudinal study.
AB  - BACKGROUND: We assessed mobility in different life stages over a 29-year period
      from adolescence through adulthood and its correlation with psychosocial stress
      and vital exhaustion at ages 32 and 42 years. METHODS: Data were derived from the
      Amsterdam Growth and Health Longitudinal Study, an observational longitudinal
      study of 420 boys and girls from age 13 to 42 years. Measurements included
      cumulative frequency of geographic relocation (CFGR), psychosocial stress
      (measured by a Dutch scale of experienced stress, VOEG-13), vital exhaustion
      (measured by the Maastricht Questionnaire, MQ), demographics, socioeconomic
      status, and other background characteristics. RESULTS: From 1976 to 2006, total
      CFGR was 3.56 +/- 1.89 (range 0-13). Frequent geographic relocation during 2 life
      stages (age 22-32 years and 33-42 years) was significantly interrelated; however,
      this was not evident at age 13 to 21 years, which suggests a unique exposure to
      relocation during adolescence and youth. After adjusting for anticipated
      confounders, higher cumulative frequencies of residential changes during
      adolescence and youth were markedly associated with psychosocial stress and vital
      exhaustion at ages 32 and 42 years. CONCLUSIONS: Frequent geographic relocation
      during adolescence and youth was an indicator of psychosocial stress and vital
      exhaustion in the transition to middle adulthood. Further consideration of the
      pathways in this web of causation may aid in stress prevention and minimize
      negative consequences.

PMID- 22863986
TI  - Secular trends in blood pressure among Japanese schoolchildren: a population
      based annual survey from 1994 to 2010.
AB  - BACKGROUND: Monitoring secular trends in blood pressure (BP) among children is
      important in predicting subsequent hypertension and cardiovascular disease. We
      investigated secular trends in BP using data from population-based annual
      screenings of Japanese schoolchildren. METHODS: The participants were 10 894
      children (all fourth graders between 1994 and 2010 and all seventh graders
      between 1997 and 2010) living in the town of Ina in Saitama Prefecture, Japan.
      Body height, weight, and BP were measured, after which children were classified
      as non-overweight, overweight, or obese. Trends in variables relative to calendar
      year were analyzed using regression models. RESULTS: Systolic BP was
      significantly associated with calendar year among fourth- and seventh-grade boys
      (-0.350 and -0.434 mm Hg/year, respectively) and fourth- and seventh-grade girls
      (-0.513 and -0.473 mm Hg/year, respectively) (all P < 0.001), respectively, over
      time. Systolic BP and calendar year were significantly negatively correlated
      regardless of physique or sex among all fourth graders, but not among obese
      seventh-grade girls. In addition, diastolic BP and calendar year did not
      significantly correlate among seventh-grade overweight or obese boys or obese
      seventh-grade girls. CONCLUSIONS: BP decreased among fourth-grade schoolchildren
      in Ina during the past 17 years, regardless of sex or physique. However, BP and
      calendar year did not significantly correlate among obese seventh graders.

PMID- 22863987
TI  - Amphibacillus marinus sp. nov., a member of the genus Amphibacillus isolated from
      marine mud.
AB  - A gram-positive, spore-forming, rod-shaped bacterium, designated J1(T) was
      isolated from deep-sea mud collected from the South China Sea and subjected to
      polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that J1(T) clustered with the type strains of Amphibacillus
      cookii, Amphibacillus sediminis and Amphibacillus jilinensis and exhibited a
      range of similarity of 93.9-97.0 % to members of the genus Amphibacillus. The DNA
      G+C content was 36.7 mol%. Chemotaxonomic analysis showed no quinones, and the
      cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid for
      strain J1(T). The major cellular fatty acids were iso-C15 : 0 and anteiso-C15 :
      0. Strain J1(T) was positive for catalase activity and negative for oxidase
      activity. On the basis of phylogenetic position and phenotypic properties, strain
      J1(T) represents a novel species of the genus Amphibacillus and the name
      Amphibacillus marinus sp. nov. is proposed. The type strain is J1(T) ( = CGMCC
      1.10434(T) = JCM 17099(T)).

PMID- 22863985
TI  - DNA methylation in peripheral blood: a potential biomarker for cancer molecular
      epidemiology.
AB  - Aberrant DNA methylation is associated with cancer development and progression.
      There are several types of specimens from which DNA methylation pattern can be
      measured and evaluated as an indicator of disease status (from normal biological
      process to pathologic condition) and even of pharmacologic response to therapy.
      Blood-based specimens such as cell-free circulating nucleic acid and DNA
      extracted from leukocytes in peripheral blood may be a potential source of
      noninvasive cancer biomarkers. In this article, we describe the characteristics
      of blood-based DNA methylation from different biological sources, detection
      methods, and the factors affecting DNA methylation. We provide a comprehensive
      literature review of blood-based DNA methylation as a cancer biomarker and focus
      on the study of DNA methylation using peripheral blood leukocytes. Although DNA
      methylation patterns measured in peripheral blood have great potential to be
      useful and informative biomarkers of cancer risk and prognosis, large systematic
      and unbiased prospective studies that consider biological plausibility and data
      analysis issues will be needed in order to develop a clinically feasible blood
      based assay.

PMID- 22863989
TI  - Moniliella carnis sp. nov. and Moniliella dehoogii sp. nov., two novel species of
      black yeasts isolated from meat processing environments.
AB  - Thirteen strains of yeasts typical of the genus Moniliella were isolated from
      fermenting meat and meat processing tools in Vietnam. PCR fingerprints generated
      by primer (GAC)(5) subdivided the strains into two distinctive genetic groups. In
      a phylogenetic tree based on D1/D2 large subunit rRNA gene sequences, the strains
      formed a well-supported clade with Moniliella spathulata and Moniliella
      suaveolens but represented two new lineages. The names Moniliella carnis sp. nov.
      and Moniliella dehoogii sp. nov. are proposed. The two novel species can be
      distinguished from each other and from known species of Moniliella based on
      phenotypic characteristics. It is assumed that the yeasts were associated with
      fatty substances that contaminated the meat processing tools. The type strain of
      Moniliella carnis is KFP 246(T) ( = CBS 126447(T) = NRRL Y-48681(T)) and the type
      strain of Moniliella dehoogii is KFP 211(T) ( = CBS 126564(T) = NRRL Y-48682(T)).

PMID- 22863988
TI  - Metallibacterium scheffleri gen. nov., sp. nov., an alkalinizing
      gammaproteobacterium isolated from an acidic biofilm.
AB  - A Gram-stain-negative, non-motile, facultatively anaerobic, acid-tolerant rod,
      designated strain DKE6(T), was isolated from an acidic biofilm (pH 2.5) harvested
      in the pyrite mine Drei Kronen und Ehrt in Germany. The isolate grew optimally at
      pH 5.5, between 25 and 30  degrees C and only with casein as the carbon and
      energy source; although a variety of sugars were tested as growth substrates,
      none supported growth of the isolate. During casein consumption, strain DKE6(T)
      produced ammonium, which led to an alkalinization of the medium. This is a
      possible strategy to raise the pH in the direct vicinity of the cell and hence
      modulate the pH towards the growth optimum. The predominant fatty acids (>5 %)
      were iso-C11 : 0 3-OH, iso-C15 : 0, iso-C17 : 0 and iso-C17 : 1omega9c. The DNA
      G+C content was 66.6 %. Strain DKE6(T) was not able to oxidize iron or
      thiosulfate. Iron reduction was detected. The isolate showed 93.3 % 16S rRNA gene
      sequence similarity to the most closely related cultivable strain, Dokdonella
      koreensis DS-123(T), but <93.2 % sequence similarity with other type strains of
      closely related type species of the Gammaproteobacteria. On the basis of
      physiological and biochemical data, the isolate is considered to represent a
      novel species of a new genus in the class Gammaproteobacteria, for which we
      propose the name Metallibacterium scheffleri gen. nov., sp. nov. The type strain
      of the type species is DKE6(T) ( = DSM 24874(T) = JCM 17596(T)).

PMID- 22863990
TI  - Naumovozyma baii sp. nov., an ascomycetous yeast species isolated from rotten
      wood in a tropical forest.
AB  - Two strains isolated from rotten wood were included in the Saccharomyces group
      based on morphological characteristics. However, rRNA gene sequence analyses
      (including the 18S rRNA gene, 26S rRNA gene D1/D2 domain and internal transcribed
      spacer region) indicated that these two strains represent a novel species of
      Naumovozyma, for which the name Naumovozyma baii sp. nov. is proposed (type
      strain: BW 22(T) = CGMCC 2.04520(T) = CBS 12642(T)). The MycoBank number of the
      new species is MB800484.

PMID- 22863991
TI  - Environmental contextualisation of potential toxic elements and polycyclic
      aromatic hydrocarbons in biochar.
AB  - Nine dissimilar biochars, produced from varying feedstock at different pyrolysis
      temperatures, are appraised with respect to concentrations of potentially toxic
      elements, specifically, metals, metalloids and polycyclic aromatic hydrocarbons
      (PAHs). Concentrations of the metals and metalloids varied with the following
      ranges (mg kg(-1)): 0.02-0.94, Cd; 0.12-6.48, Cr; 0.04-13.2, Cu; 0.1-1.37, Ni;
      0.06-3.87, Pb; 0.94-207, Zn and 0.03-0.27, As. Sigma(16)PAH concentrations (16
      Environmental Protection Agency (EPA) PAHs) range between 0.08 mg kg(-1) to 8.7
      mg kg(-1). Subsequent comparison with background soil concentrations,
      concentration applied to the regulation of composted materials (Publicly
      Available Specification (PAS 100)) and European Union (EU) regulations relating
      to the application of sewage sludge to agricultural land suggest low risk
      associated with the concentrations of PTEs observed in biochar. Collectively,
      results suggest that environmental impacts attributable to metals, metalloids and
      PAHs associated with biochar following its application to soil are likely to be
      minimal.

PMID- 22863992
TI  - The illegal cigarette market in a socioeconomically deprived inner-city area: the
      case of the South Bronx.
AB  - OBJECTIVE: To determine the scope of the cigarette black market in a
      socioeconomically deprived inner-city area in the US, taking the South Bronx in
      New York City as a case study. DESIGN: The South Bronx Litter Pack Survey
      collected discarded cigarette packs (n=497) along 30 randomised census tracts to
      quantify the prevalence of counterfeit, legal and out-of-state tax stamps.
      RESULTS: It was found that 76.2% of cigarette packs collected avoided the
      combined New York City and State tax. More specifically, 57.9% were untaxed
      (counterfeit or bearing no tax stamp), for 15.8% taxes were paid outside of New
      York City (including other states and New York State only). Only 19.4% of tax
      stamps collected indicated that New York City and New York State taxes were paid.
      4.4% of the cigarette packs could not be analysed because the tax stamps were not
      discernible. The finding that the majority of cigarettes did not have a tax stamp
      or bore a counterfeit tax stamp suggests that these cigarettes were being
      bootlegged, most likely from Native American Reservations. CONCLUSIONS: The
      present study highlights the importance of examining the illegal cigarette market
      in socioeconomically deprived regions of the US, where tax avoidance and black
      market activities appear to far exceed levels found elsewhere in the country
      including Chicago and New York City at large.

PMID- 22863993
TI  - Hookah steam stones: smoking vapour expands from electronic cigarettes to
      waterpipes.

PMID- 22863994
TI  - A rat model for stable chronic obstructive pulmonary disease induced by cigarette
      smoke inhalation and repetitive bacterial infection.
AB  - To develop a stable chronic obstructive pulmonary disease (COPD) model in rats.
      Sprague-Dawley rats were treated with cigarette-smoke inhalation (CSI) for 12
      weeks, repetitive bacterial infection (RBI) for 8 weeks, or the combination of
      the two (CCR) for 12 weeks and followed up for the additional 20 weeks. Tidal
      volume (V(T)), peak expiratory flow (PEF) and 50% V(T) expiratory flow (EF(50)),
      histological changes in the lungs, and levels of the cytokines tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-8, and IL-10 in serum and bronchial alveolar
      lavage fluid (BALF) were examined at intervals during the 32 week study period.
      The right ventricular hypertrophy index (RVHI) was also determined at the same
      times. V(T), PEF, and EF(50) were decreased in rats with COPD compared to the
      control. The expression of TNF-alpha, IL-8 and IL-10 increased in both serum and
      BALF with a similar trend. Bronchiole and arteriole wall thickness and the degree
      of bronchiole stenosis and alveolar size increased in COPD rats. RVHI was reduced
      gradually following the treatment. All of these changes were more pronounced in
      the CCR-treatment group than in the other groups. Our results have shown that CSI
      or RBI alone can induce COPD in rats, but that the combination of CSI with RBI
      induces a stable COPD that has more similarity to complications seen in patients
      with COPD. This combination may therefore provide a more appropriate model for
      study of human COPD.

PMID- 22863995
TI  - Retigeric acid B enhances the efficacy of azoles combating the virulence and
      biofilm formation of Candida albicans.
AB  - Candida albicans is one of the most prevalent human opportunistic pathogens. C.
      albicans undergoes a yeast-to-hyphal transition that has been identified as a
      virulence factor as well as a critical element for mature biofilm formation. A
      previous study in our lab showed retigeric acid B (RAB), a lichen derived
      pentacyclic triterpenoid, displayed synergistic antifungal activity with azoles.
      We now showed that this combination also proved to be adequate in combating the
      formation of hyphae in vitro. In vivo tests with mice demonstrated RAB could
      markedly enhance the efficacy of fluconazole to promote the host's longevity
      through inhibiting hyphae formation and adherence to host cells. It was also
      observed that RAB and azoles interacted synergistically to block the formation of
      biofilm. Our data suggested the attenuated yeast-to-hyphal switch contributed to
      the defect of mature biofilm formation. Moreover, quantitative real-time
      polymerase chain reaction (qPCR) analysis showed RAB could reduce the transcript
      level of MDR1, a multidrug efflux pump, and caused a slight transcriptional
      reduction for another drug pump related gene CDR1. Taken together, our work
      provides a potential application to combat candidiasis using the combination of
      RAB and azoles.

PMID- 22863997
TI  - The value of networking.

PMID- 22863996
TI  - Validation of a detailed scoring checklist for use during advanced cardiac life
      support certification.
AB  - INTRODUCTION: Defining valid, reliable, defensible, and generalizable standards
      for the evaluation of learner performance is a key issue in assessing both
      baseline competence and mastery in medical education. However, before setting
      these standards of performance, the reliability of the scores yielding from a
      grading tool must be assessed. Accordingly, the purpose of this study was to
      assess the reliability of scores generated from a set of grading checklists used
      by nonexpert raters during simulations of American Heart Association (AHA)
      Megacodes. METHODS: The reliability of scores generated from a detailed set of
      checklists, when used by 4 nonexpert raters, was tested by grading team leader
      performance in 8 Megacode scenarios. Videos of the scenarios were reviewed and
      rated by trained faculty facilitators and a group of nonexpert raters. The videos
      were reviewed "continuously" and "with pauses." The grading made by 2 content
      experts served as the reference standard, and 4 nonexpert raters were used to
      test the reliability of the checklists. RESULTS: Our results demonstrate that
      nonexpert raters are able to produce reliable grades when using the checklists
      under consideration, demonstrating excellent intrarater reliability and agreement
      with a reference standard. The results also demonstrate that nonexpert raters can
      be trained in the proper use of the checklist in a short amount of time, with no
      discernible learning curve thereafter. Finally, our results show that a single
      trained rater can achieve reliable scores of team leader performance during AHA
      Megacodes when using our checklist in a continuous mode because measures of
      agreement in total scoring were very strong [Lin's (Biometrics 1989;45:255-268)
      concordance correlation coefficient, 0.96; intraclass correlation coefficient,
      0.97]. CONCLUSIONS: We have shown that our checklists can yield reliable scores,
      are appropriate for use by nonexpert raters, and are able to be used during
      continuous assessment of team leader performance during the review of a simulated
      Megacode. This checklist may be more appropriate for use by advanced cardiac life
      support instructors during Megacode assessments than the current tools provided
      by the AHA.

PMID- 22864000
TI  - Associated morbidities to congenital diaphragmatic hernia and a relationship to
      human milk.
AB  - The majority of what is known in the recent literature regarding human milk
      studies in the neonatal intensive care setting is specific to term and/or preterm
      infants (including very-low-birth-weight preterm infants). However, there is a
      lack of human milk and breastfeeding literature concerning infants with
      congenital anomalies, specifically infants diagnosed with congenital
      diaphragmatic hernia (CDH). By applying human milk research conducted among other
      populations of infants, this article highlights how human milk may have a
      significant impact on infants with CDH. Recent human milk studies are reviewed
      and then applied to the CDH population in regard to respiratory and
      gastrointestinal morbidities, as well as infection and length of stay. In
      addition, clinical implications of these relationships are discussed and
      suggestions for future research are presented.

PMID- 22864001
TI  - Thyroid hormones in the neonate: an overview of physiology and clinical
      correlation.
AB  - This article reviews the pathological actions of the thyroid hormones in the
      neonate. A review of the thyroid gland, thyroid hormones, fetal thyroid
      development, and healthy neonatal thyroid actions is explored as a basis to
      comprehend common thyroid diseases.

PMID- 22864003
TI  - The impact of wealth on the cognitive development of children who were preterm
      infants.
AB  - PURPOSE: : The purpose of this study was to explore the influence wealth has on
      cognitive development in 2-year-old children who were born preterm, and to
      determine whether racial/ethnic differences in wealth explained disparities in
      cognitive development. SUBJECTS: : A nationally representative sample of 1400
      children who were born between 22 and 36 weeks' gestation. DESIGN: : Cohort
      study. METHODS: : Secondary data analysis of the Early Childhood Longitudinal
      Survey-Birth Cohort (ECLS-B). The ECLS-B was a prospective national longitudinal
      study of infants born in the United States during the calendar year 2001 drawn
      from birth certificates in the United States. MAIN OUTCOMES: : The impact wealth
      (parental homeownership and investments) had on cognitive development at 2 years
      and whether wealth eliminated the cognitive disparity seen between white, African
      American, and Hispanic children. PRINCIPAL RESULTS: : Wealth (homeownership and
      investments) did not have an independent effect on cognitive development, but it
      did eliminate the disparity between white children and African American children
      (P >= .05). However, wealth did not eliminate the disparity in cognitive
      development between white children and Hispanic children. Hispanic children
      scored 3.91 points lower than white children (P <= .001). CONCLUSION: : In
      contrast to other follow-up studies showing persistent differences in cognitive
      development between white children and African American children, this study
      found that wealth indicators attenuated the difference. Wealth may be a more
      accurate proxy for socioeconomic status in studying factors influencing cognitive
      outcomes in children born preterm than just using measures such as maternal
      education and income. In future follow-up studies of multiracial preterm
      children, indicators that represent wealth should be included for an accurate
      representation of social economic status.

PMID- 22864004
TI  - Transfusion-associated necrotizing enterocolitis: evidence and uncertainty.
AB  - Transfusion-associated necrotizing enterocolitis (TANEC) has been described as
      necrotizing enterocolitis (NEC) that arises within 48 hours of a blood
      transfusion. It has been shown to be associated with 25% to 35% of NEC cases in
      recent studies. Evidence related to TANEC is limited to observational,
      retrospective studies. Infants who develop TANEC tend to be smaller, born
      preterm, more severely ill, and develop NEC after 30 days of age. Evidence in 2
      studies support holding feedings during transfusion to protect the preterm gut
      from the cascade of events that lead to NEC, but higher quality research,
      including prospective randomized controlled trials, is needed to evaluate the
      effect of feeding on TANEC.

PMID- 22864005
TI  - Symptoms of acute stress disorder in mothers of premature infants.
AB  - PURPOSE: : To determine whether significant symptoms of acute stress disorder
      (ASD) are present in mothers of premature infants in the neonatal intensive care
      unit (NICU). SUBJECTS: : Forty mothers of premature infants born less than 33
      weeks and admitted into NICU. DESIGN: : Prospective, cohort, within-subjects.
      METHODS: : Mothers completed the Stanford Acute Stress Reaction Questionnaire,
      Edinburgh Postnatal Depression Scale, and the Acute Stress Disorder Interview to
      explore the number and severity of stress-related symptoms at 2 separate time
      periods, 7 to 10 days after birth, and 1 month after birth. RESULTS: : Twenty
      eight percent of the mothers met diagnostic criteria of ASD at 7 to 10 days after
      birth, and at 1 month after birth ASD symptoms persisted. The majority of the
      mothers described premature birth as a traumatic stressor. The most commonly met
      criteria were dissociation and anxiety. Significant symptoms of depression were
      found in 43% of mothers and persisted 1 month after birth. Rates of depression
      and moderate to severe symptoms of ASD were significantly related in mothers at 1
      week and at 1 month after birth. CONCLUSIONS: : The premature birth experience is
      traumatic for mothers and may lead to various emotional responses including
      stress-related symptoms such as depression and/or ASD. Mothers with significant
      symptoms of depression and those with symptoms of stress seem to be more at risk
      for developing symptoms of ASD.

PMID- 22864006
TI  - Effect of breast milk on hospital costs and length of stay among very low-birth
      weight infants in the NICU.
AB  - PURPOSE: Care of the very low-birth-weight (VLBW) infant is associated with
      prolonged hospitalization and increased hospital costs. Specific complications of
      prematurity, including necrotizing enterocolitis (NEC), late-onset sepsis (LOS),
      and feeding intolerance, contribute to increased cost and length of
      hospitalization in this population. The provision of breast milk to VLBW infants
      has been associated with decreased incidence of NEC and LOS as well as fewer days
      required to achieve full enteral feedings. The purpose of this study was to
      determine the impact of breast milk on length of hospitalization and hospital
      costs among VLBW infants in the neonatal intensive care unit (NICU). SUBJECTS: A
      total of 80 infants weighing less than 1500 g, born prior to 32 weeks' gestation
      and who remained in the home hospital until discharge. DESIGN: This descriptive
      comparative study examined cost of hospitalization and length of stay between 2
      groups of VLBW premature infants fed either exclusively formula (n = 40) or at
      least 50% breast milk (n = 40) during their hospitalization. METHODS: A
      retrospective chart review was used to collect information concerning patient
      demographics, discharge information, and nutritional variables. Information
      regarding hospital costs was obtained from the hospital's patient accounting
      office. MAIN OUTCOME MEASURES: Independent t tests were used to compare
      demographic data, length of hospitalization, and cost of care between the 2
      groups. PRINCIPAL RESULTS: No statistically significant differences in length of
      stay or cost of care were found between infants fed at least 50% breast milk and
      those who were exclusively formula fed. Descriptive data concerning length of
      stay and cost of care for VLBW infants and those infants weighing less than 1000
      g are presented. CONCLUSION: This article presents a descriptive comparative
      study on the effect of providing at least 50% breast milk feedings compared with
      formula feeding on days to discharge and cost of hospitalization in VLBW infants
      in the NICU. It also provides information concerning cost of care and length of
      stay in VLBW and infants weighing less than 1000 g.

PMID- 22864007
TI  - Job satisfaction of neonatal intensive care nurses.
AB  - PURPOSE: The purpose of this study was to describe the job satisfaction of
      neonatal intensive care unit (NICU) nurses in the Midwestern United States. The
      factors explored in job satisfaction were monetary compensation (pay), job
      stress, caring for patients in stressful situations, level of autonomy,
      organizational support, level of knowledge of the specialty, work environment,
      staffing levels, communication with physicians, communication with neonatal nurse
      practitioners, interdisciplinary communication, team spirit, and the amount of
      required "floating" to other nursing units. SUBJECTS: Participants were 109 NICU
      nurses working as either staff nurses (n = 72) or advanced practice nurses (n =
      37). Of the participants, 96% worked in a level 3 NICU. DESIGN: A descriptive,
      correlational design was used to study job satisfaction among NICU nurses.
      METHODS: Nurses were recruited at 2 regional NICU conferences in 2009 and 2010.
      The questionnaire was a researcher-developed survey consisting of 14 questions in
      a Likert-type response rating 1 to 5, with an area for comments. Descriptive
      statistics and correlations were used to analyze the resulting data. MAIN OUTCOME
      MEASURES: The majority of participants were moderately satisfied overall in their
      current position and workplace (mean ranking = 4.07 out of 5.0). Kendall's Tau b
      (TB) revealed that the strongest positive correlations were between
      organizational support and team spirit with overall job satisfaction (TB = 0.53).
      RESULTS: : The individual factors with the highest mean scores were caring for
      patients in a stressful situation, level of autonomy, and communication between
      nurses and neonatal nurse practitioners. This indicates that our population of
      NICU nurses feels most satisfied caring for patients in stressful situations (m =
      4.48), are satisfied with their level of autonomy (M = 4.17), and are satisfied
      with the interdisciplinary communication in their units (m = 4.13). CONCLUSIONS:
      Nurses in the NICU are relatively satisfied with their jobs. The small sample
      size (n = 109) of Midwest NICU nurses proves to be a limitation for
      generalization. Additional research is needed to further evaluate nursing role,
      educational level, and job satisfaction in the NICU.

PMID- 22864008
TI  - SF4.N(C2H5)3: the first conclusively characterized SF4 adduct with an organic
      base.
AB  - Sulfur tetrafluoride and triethylamine react at low temperatures to form a 1:1
      adduct. The unambiguous characterization of the SF(4).N(C(2)H(5))(3), which is
      only stable at low temperature, proves the Lewis acid property of SF(4) towards
      organic Lewis bases. The S-N bond has a length of 2.384(2) A and is an
      archetypical example of a dative S(IV) <- N bonding modality.

PMID- 22864009
TI  - Rectus femoris muscle injuries in football: a clinically relevant review of
      mechanisms of injury, risk factors and preventive strategies.
AB  - Quadriceps muscle strains frequently occur in sports that require repetitive
      kicking and sprinting, and are common in football in its different forms around
      the world. This paper is a review of aetiology, mechanism of injury and the
      natural history of rectus femoris injury. Investigating the mechanism and risk
      factors for rectus femoris muscle injury aims to allow the development of a
      framework for future initiatives to prevent quadriceps injury in football
      players.

PMID- 22864010
TI  - Practical management of sudden cardiac arrest on the football field.
AB  - Sudden cardiac arrest (SCA) remains a tragic occurrence on the football field.
      The limits of preparticipation cardiovascular screening make it compulsory that
      prearranged emergency medical services be available at all football matches to
      immediately respond to any collapsed player. Management of SCA involves prompt
      recognition, immediate cardiopulmonary resuscitation (CPR) and early
      defibrillation. Any football player who collapses without contact with another
      player or obstacle should be regarded as being in SCA until proven otherwise. An
      automated external defibrillator (AED), or manual defibrillator if an AED is not
      available, should be immediately accessible on the field during competitions.
      This study presents guidelines for a practical and systematic approach to the
      management of SCA on the football field.

PMID- 22864011
TI  - Extranodal NK/T-cell lymphoma, nasal type, presenting pseudoepitheliomatous
      hyperplasia mimicking squamous cell carcinoma.

PMID- 22864012
TI  - Impact of the accuracy of automatic tumour functional volume delineation on
      radiotherapy treatment planning.
AB  - Over the past few years several automatic and semi-automatic PET segmentation
      methods for target volume definition in radiotherapy have been proposed. The
      objective of this study is to compare different methods in terms of dosimetry.
      For such a comparison, a gold standard is needed. For this purpose, realistic
      GATE-simulated PET images were used. Three lung cases and three H&N cases were
      designed with various shapes, contrasts and heterogeneities. Four different
      segmentation approaches were compared: fixed and adaptive thresholds, a fuzzy C
      mean and the fuzzy locally adaptive Bayesian method. For each of these target
      volumes, an IMRT treatment plan was defined. The different algorithms and
      resulting plans were compared in terms of segmentation errors and ground-truth
      volume coverage using different metrics (V(95), D(95), homogeneity index and
      conformity index). The major differences between the threshold-based methods and
      automatic methods occurred in the most heterogeneous cases. Within the two
      groups, the major differences occurred for low contrast cases. For homogeneous
      cases, equivalent ground-truth volume coverage was observed for all methods but
      for more heterogeneous cases, significantly lower coverage was observed for
      threshold-based methods. Our study demonstrates that significant dosimetry errors
      can be avoided by using more advanced image-segmentation methods.

PMID- 22864013
TI  - Association between waist-to-height ratio and metabolic risk factors in Korean
      adults with normal body mass index and waist circumference.
AB  - There is little consensus on the best obesity index associated with metabolic
      risk factors among the population with normal both body mass index (BMI) and
      waist circumference (WC). We therefore evaluated the association between
      anthropometric indices and metabolic risk factors in a Korean population with
      normal BMI and WC. This cross-sectional study involved 2,952 participants aged 20
      79 years who had normal BMI and WC, based on the Fourth Korea National Health and
      Nutrition Examination Surveys conducted in 2008. The receiver operating
      characteristic (ROC) curves were generated to identify the optimal measurement of
      obesity for the prediction of metabolic risk factors in this population. The area
      under the ROC curve value for waist-to-height ratio (WHtR) in prediction of
      metabolic syndrome (MetS) and its components was higher than that for BMI and WC.
      Among individuals with normal BMI and WC, prevalence of all metabolic risk
      factors and MetS significantly increased across the quartiles of WHtR in both men
      and women. After adjustment for potential confounders, the Odds Ratios (95%
      confidence intervals) for MetS in the second, third, and fourth quartiles of WHtR
      compared to the first quartile of WHtR were 3.53 (2.12-5.89), 6.06 (3.52-10.43),
      and 7.11 (4.08-12.38) in men, and 1.66 (1.01-2.72), 2.79 (1.81-4.30), and 2.82
      (1.76-4.52) in women, respectively. In conclusion, WHtR has the best predictive
      value for evaluating the metabolic risk factors compared to BMI or WC alone among
      subjects with normal BMI and WC.

PMID- 22864014
TI  - The effects of simulated patients and simulated gynecologic models on student
      anxiety in providing IUD services.
AB  - INTRODUCTION: Midwifery students experience high levels of stress during their
      initial clinical practices. Addressing the learner's source of anxiety and
      discomfort can ease the learning experience and lead to better outcomes. The aim
      of this study was to find out the effect of a simulation-based course, using
      simulated patients and simulated gynecologic models on student anxiety and
      comfort while practicing to provide intrauterine device (IUD) services. METHODS:
      Fifty-six eligible midwifery students were randomly allocated into simulation
      based and traditional training groups. They participated in a 12-hour workshop in
      providing IUD services. The simulation group was trained through an educational
      program including simulated gynecologic models and simulated patients. The
      students in both groups then practiced IUD consultation and insertion with real
      patients in the clinic. The students' anxiety in IUD insertion was assessed using
      the "Spielberger anxiety test" and the "comfort in providing IUD services"
      questionnaire. RESULTS: There were significant differences between students in 2
      aspects of anxiety including state (P < 0.001) and trait (P = 0.024) and the
      level of comfort (P = 0.000) in providing IUD services in simulation and
      traditional groups. "Fear of uterine perforation during insertion" was the most
      important cause of students' anxiety in providing IUD services, which was
      reported by 74.34% of students. CONCLUSIONS: Simulated patients and simulated
      gynecologic models are effective in optimizing students' anxiety levels when
      practicing to deliver IUD services. Therefore, it is recommended that simulated
      patients and simulated gynecologic models be used before engaging students in
      real clinical practice.

PMID- 22864015
TI  - Impact of neck dissection on scapular muscle function: a case-controlled
      electromyographic study.
AB  - OBJECTIVE: To assess the dynamic activity of scapular muscles in patients with
      accessory nerve dysfunction after neck dissection surgery, compared with both
      their unaffected side and with age- and sex-matched controls. DESIGN: A case
      control investigation. SETTING: Physiotherapy department of a hospital.
      PARTICIPANTS: Two groups of 10 participants were recruited. One group consisted
      of neck dissection patients with demonstrated clinical signs of accessory nerve
      injury. The second group was composed of matched healthy individuals.
      INTERVENTIONS: Surface electromyographic activity of the upper trapezius, middle
      trapezius, rhomboid major, and serratus anterior muscles was compared dynamically
      during scapular strengthening exercises. MAIN OUTCOME MEASURES: Electromyographic
      activity comparisons were made between the neck dissection affected side, the
      neck dissection unaffected side, and the matched healthy control side. Raw data
      and data expressed as a percentage of maximal voluntary isometric contraction
      were compared. RESULTS: The neck dissection affected side demonstrated
      significantly less upper trapezius and middle trapezius muscle activity compared
      with the neck dissection unaffected side and matched control group. The neck
      dissection unaffected side had significantly less upper trapezius muscle activity
      than the matched control group. CONCLUSIONS: Trapezius muscle activity is
      significantly reduced in accessory nerve shoulder dysfunction as a result of neck
      dissection, both in the affected and unaffected sides. This needs to be
      considered in the rehabilitation of this patient group.

PMID- 22864016
TI  - Changes of timing variables in swallowing of boluses with different viscosities
      in patients with dysphagia.
AB  - OBJECTIVES: To evaluate the timing of the swallowing process and the effect of
      bolus viscosity on swallowing. DESIGN: Prospective observational study. SETTING:
      General teaching hospital, rehabilitation unit. PARTICIPANTS: We enrolled
      patients with dysphagia (n=82) in a videofluoroscopic swallowing study (VFSS)
      from January 13, 2009, to October 22, 2009. Based on VFSS results, we classified
      patients as "thin-fluid aspirators" (n=40) or as "nonaspirators" (n=42).
      INTERVENTIONS: Swallowing of a 5-mL thick bolus and a 5-mL thin bolus in all
      patients. MAIN OUTCOME MEASURES: Kinematic analysis of various variables during
      the swallowing process (pharyngeal phase), including epiglottis contact with the
      bolus, laryngeal elevation, pharyngeal constriction, and upper esophageal
      sphincter opening. RESULTS: In both groups, the thin bolus arrived at the
      vallecular pouch earlier than the thick bolus. During swallowing of the thick
      bolus, the thin-fluid aspirators had a delayed latency of upper esophageal
      sphincter opening, delayed laryngeal elevation to peak level, and significantly
      longer rise time of laryngeal elevation. CONCLUSIONS: Our results indicate clear
      differences in the degree of adaptation to bolus viscosity between patients
      classified as thin-fluid aspirators and as nonaspirators. These differences were
      mainly in activities of laryngeal elevators rather than pharyngeal constrictors.

PMID- 22864017
TI  - Pain and post-traumatic stress disorder symptoms during inpatient rehabilitation
      among operation enduring freedom/operation iraqi freedom veterans with spinal
      cord injury.
AB  - OBJECTIVE: To examine the frequency of post-traumatic stress disorder (PTSD)
      symptoms and pain, and how PTSD symptoms were associated with pain severity
      ratings and the longitudinal course of pain during inpatient rehabilitation for
      spinal cord injury (SCI) among veterans of the Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OIF) conflicts. DESIGN: Longitudinal
      analysis of data gathered from electronic medical records. SETTING: SCI specialty
      care centers within the Department of Veterans Affairs. PARTICIPANTS: Veterans of
      the OEF/OIF conflicts (N=87) who received inpatient rehabilitation for SCI and
      disorders at Department of Veterans Affairs SCI centers between May 2003 and
      October 2009. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): PTSD
      screening at start of rehabilitation and pain numeric rating scale measurements
      completed throughout rehabilitation. Cut-scores were used to categorize
      participants into 1 of 4 groups on the basis of scores at the start of
      rehabilitation: Pain and PTSD, Pain Alone, PTSD Alone, Neither Condition.
      RESULTS: Comorbid pain and PTSD symptoms were more common than either condition
      alone, and nearly as common as not having either condition. Participants with
      pain at the start of rehabilitation (Pain and PTSD, Pain-Alone groups) showed
      declines in pain ratings over the course of rehabilitation. In contrast,
      participants in the PTSD-Alone group showed increasing pain over the course of
      rehabilitation. CONCLUSIONS: Pain and PTSD symptoms may be more likely to
      manifest as comorbidities than as isolated conditions during inpatient
      rehabilitation. Assessment routines and care plans should be prepared with
      comorbidities as a foremost concern. It is advisable to screen for pain and PTSD
      at multiple time points during inpatient rehabilitation to detect new or emerging
      concerns.

PMID- 22864018
TI  - Influence of hemodynamic variations on the pharmacokinetics of landiolol in
      patients undergoing cardiovascular surgery.
AB  - Although landiolol is useful in the emergency management of atrial fibrillation,
      atrial flutter, and tachycardia, as well as in perioperative arrhythmia control,
      the influence of hemodynamic changes on the pharmacokinetics of landiolol is
      unknown. We investigated the influence of hemodynamic variation and the following
      hepatocirculatory changes after systemic heparinization on the pharmacokinetics
      of landiolol in patients undergoing cardiovascular surgery under cardiopulmonary
      bypass. Cardiac output and cardiac index (CI) were continuously monitored in 19
      patients using an arterial pressure-based cardiac output monitor. The middle and
      right hepatic venous blood flow indexes (mHVBFI and rHVBFI) were measured by
      transesophageal echocardiography, and hemodynamic data were collected at points
      (T1-T3) as follows: T1, before administration of heparin and after sternotomy;
      T2, just before systemic heparinization (300 U/kg); T3, 10 min after T2. The
      plasma concentration of landiolol was measured by HPLC at the same point. After
      administration of heparin, mean arterial blood pressure, CI, mHVBFI, and rHVBFI
      were significantly decreased (<0.05). Heart rate was not significantly changed.
      After systemic heparinization, the landiolol concentration was significantly
      decreased from 0.407+/-0.251 ug.mL(-1) to 0.232+/-0.207 ug.mL(-1) (<0.01). There
      was no significant difference between T1 and T2 (=0.88). In conclusion, the
      plasma concentration of landiolol was decreased by diminished CI due to systemic
      heparinization, but not affected by the change of hepatic blood flow.

PMID- 22864019
TI  - Mutation of sec63 in zebrafish causes defects in myelinated axons and liver
      pathology.
AB  - Mutations in SEC63 cause polycystic liver disease in humans. Sec63 is a member of
      the endoplasmic reticulum (ER) translocon machinery, although it is unclear how
      mutations in SEC63 lead to liver cyst formation in humans. Here, we report the
      identification and characterization of a zebrafish sec63 mutant, which was
      discovered in a screen for mutations that affect the development of myelinated
      axons. Accordingly, we show that disruption of sec63 in zebrafish leads to
      abnormalities in myelinating glia in both the central and peripheral nervous
      systems. In the vertebrate nervous system, segments of myelin are separated by
      the nodes of Ranvier, which are unmyelinated regions of axonal membrane
      containing a high density of voltage-gated sodium channels. We show that sec63
      mutants have morphologically abnormal and reduced numbers of clusters of voltage
      gated sodium channels in the spinal cord and along peripheral nerves.
      Additionally, we observed reduced myelination in both the central and peripheral
      nervous systems, as well as swollen ER in myelinating glia. Markers of ER stress
      are upregulated in sec63 mutants. Finally, we show that sec63 mutants develop
      liver pathology. As in glia, the primary defect, detectable at 5 dpf, is
      fragmentation and swelling of the ER, indicative of accumulation of proteins in
      the lumen. At 8 dpf, ER swelling is severe; other pathological features include
      disrupted bile canaliculi, altered cytoplasmic matrix and accumulation of large
      lysosomes. Together, our analyses of sec63 mutant zebrafish highlight the
      possible role of ER stress in polycystic liver disease and suggest that these
      mutants will serve as a model for understanding the pathophysiology of this
      disease and other abnormalities involving ER stress.

PMID- 22864020
TI  - Cognitive effects of dopamine depletion in the context of diminished
      acetylcholine signaling capacity in mice.
AB  - A subset of patients with Parkinson's disease acquires a debilitating dementia
      characterized by severe cognitive impairments (i.e. Parkinson's disease dementia;
      PDD). Brains from PDD patients show extensive cholinergic loss as well as
      dopamine (DA) depletion. We used a mutant mouse model to directly test whether
      combined cholinergic and DA depletion leads to a cognitive profile resembling
      PDD. Mice carrying heterozygous deletion of the high-affinity, hemicholinium-3
      sensitive choline transporter (CHT(HET)) show reduced levels of acetylcholine
      throughout the brain. We achieved bilateral DA depletion in CHT(HET) and wild
      type (WT) littermates via intra-striatal infusion of 6-hydroxydopamine (6-OHDA),
      or used vehicle as control. Executive function and memory were evaluated using
      rodent versions of cognitive tasks commonly used with human subjects: the set
      shifting task and spatial and novel-object recognition paradigms. Our studies
      revealed impaired acquisition of attentional set in the set-shifting paradigm in
      WT-6OHDA and CHT(HET)-vehicle mice that was exacerbated in the CHT(HET)-6OHDA
      mice. The object recognition test following a 24-hour delay was also impaired in
      CHT(HET)-6OHDA mice compared with all other groups. Treatment with
      acetylcholinesterase (AChE) inhibitors physostigmine (0.05 or 0.1 mg/kg) and
      donepezil (0.1 and 0.3 mg/kg) reversed the impaired object recognition of the
      CHT(HET)-6OHDA mice. Our data demonstrate an exacerbated cognitive phenotype with
      dual ACh and DA depletion as compared with either insult alone, with traits
      analogous to those observed in PDD patients. The results suggest that combined
      loss of DA and ACh could be sufficient for pathogenesis of specific cognitive
      deficits in PDD.

PMID- 22864022
TI  - Fasting hyperglycemia in the Goto-Kakizaki rat is dependent on corticosterone: a
      confounding variable in rodent models of type 2 diabetes.
AB  - The Goto-Kakizaki (GK) rat is an inbred model of type 2 diabetes (T2D); GK rats
      are lean but have hyperglycemia and increased gluconeogenesis. However, fasting
      hyperglycemia in other commonly used rodent models of T2D is associated with
      increased corticosterone, and thus the underlying mechanism for hyperglycemia
      differs significantly from T2D in humans. Information regarding corticosterone in
      the GK rat is not readily available. We studied 14- to 16-week-old GK rats in
      comparison with age-matched control Wistar-Kyoto (WK) rats. GK rats had lower
      body weights (WK: 343+/-10 g vs GK: 286+/-9 g, P<0.01), but higher plasma glucose
      concentrations (WK: 132+/-1.5 mg/dl vs GK: 210+/-11.7 mg/dl, P<0.01). This was
      associated with an ~twofold increase in PEPCK1 expression (P<0.05). However,
      these findings were also associated with elevations in plasma corticosterone and
      urinary corticosterone excretion. Ketoconazole (KTZ) treatment in GK rats reduced
      plasma corticosterone, fasting glucose (GK: 218+/-15 mg/dl vs GK-KTZ: 135+/-19
      mg/dl, P<0.01) and rates of glucose production [GK: 16.5+/-0.6 mg/(kg-minute) vs
      GK-KTZ: 12.2+/-0.9 mg/(kg-minute), P<0.01]. This was associated with an ~40%
      reduction in hepatic PEPCK1 expression as well as a 20% reduction in alanine
      turnover. Thus, hypercorticosteronemia might contribute to the diabetic phenotype
      of GK rats and should be considered as a potential confounder in rodent models of
      T2D.

PMID- 22864021
TI  - Age-related changes in core body temperature and activity in triple-transgenic
      Alzheimer's disease (3xTgAD) mice.
AB  - Alzheimer's disease (AD) is characterised, not only by cognitive deficits and
      neuropathological changes, but also by several non-cognitive behavioural symptoms
      that can lead to a poorer quality of life. Circadian disturbances in core body
      temperature and physical activity are reported in AD patients, although the cause
      and consequences of these changes are unknown. We therefore characterised
      circadian patterns of body temperature and activity in male triple transgenic AD
      mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry.
      At 4 months of age, daily temperature rhythms were phase advanced and by 6 months
      of age an increase in mean core body temperature and amplitude of temperature
      rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms
      were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase
      in mean daily activity and the amplitude of activity profiles for 3xTgAD mice
      were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food
      intake compared with Non-Tg mice. The changes in temperature did not appear to be
      solely due to increased food intake and were not cyclooxygenase dependent because
      the temperature rise was not abolished by chronic ibuprofen treatment. No beta
      amyloid (Abeta) plaques or neurofibrillary tangles were noted in the hypothalamus
      of 3xTgAD mice, a key area involved in temperature regulation, although these
      pathological features were observed in the hippocampus and amygdala of 3xTgAD
      mice from 10 months of age. These data demonstrate age-dependent changes in core
      body temperature and activity in 3xTgAD mice that are present before significant
      AD-related neuropathology and are analogous to those observed in AD patients. The
      3xTgAD mouse might therefore be an appropriate model for studying the underlying
      mechanisms involved in non-cognitive behavioural changes in AD.

PMID- 22864024
TI  - Infectious uveitis: recent advances in diagnosis and treatment.

PMID- 22864025
TI  - Outcome of phacoemulsification in eyes with cataract and cornea opacity partially
      obscuring the pupillary area.
AB  - OBJECTIVE: To evaluate the intra-operative difficulties and postoperative visual
      outcome following phacoemulisification and intraocular lens (IOL) implantation in
      eyes with cataract and a coexisting corneal opacity partially obscuring the
      pupillary area. MATERIALS AND METHODS: The study included 205 eyes of 205
      patients with cataract, an extensive corneal opacity partially obscuring the
      pupillary area and a corrected distance visual acuity (CDVA) of less than 40/200
      who had undergone phacoemulisification with IOL implantation by a single surgeon.
      The patients were followed up on day 1, day 7, 1 month and 3 months
      postoperatively. Intra-operative and post operative course and CDVA were
      evaluated. RESULTS: Seventy nine percent of the patients underwent phaco
      emulsification via superior clear corneal approach while the rest were operated
      via temporal clear corneal approach. Trypan blue (0.06%) dye assisted
      capsulorrhexis was successfully completed in all eyes with additional maneuvers
      including posterior synechiolysis and sphincterotomy. Nucleotomy with primary
      chop technique and phacoemulsification were performed uneventfully in all but one
      eye, which was converted to an extra capsular cataract extraction (ECCE). A
      foldable intraocular lens was implanted in 76 eyes, rigid IOL in 128 eyes and 1
      eye was left aphakic. The pre-operative CDVA of less than 40/200 improved to
      20/60 at the end of 3 months follow up. CONCLUSIONS: Phacoemulsification and
      intraocular lens implantation provides ambulatory and useful vision in eyes with
      coexisting cataract and corneal opacity.

PMID- 22864023
TI  - A mathematical model of weight loss under total starvation: evidence against the
      thrifty-gene hypothesis.
AB  - The thrifty-gene hypothesis (TGH) posits that the modern genetic predisposition
      to obesity stems from a historical past where famine selected for genes that
      promote efficient fat deposition. It has been previously argued that such a
      scenario is unfeasible because under such strong selection any gene favouring fat
      deposition would rapidly move to fixation. Hence, we should all be predisposed to
      obesity: which we are not. The genetic architecture of obesity that has been
      revealed by genome-wide association studies (GWAS), however, calls into question
      such an argument. Obesity is caused by mutations in many hundreds (maybe
      thousands) of genes, each with a very minor, independent and additive impact.
      Selection on such genes would probably be very weak because the individual
      advantages they would confer would be very small. Hence, the genetic architecture
      of the epidemic may indeed be compatible with, and hence support, the TGH. To
      evaluate whether this is correct, it is necessary to know the likely effects of
      the identified GWAS alleles on survival during starvation. This would allow
      definition of their advantage in famine conditions, and hence the likely
      selection pressure for such alleles to have spread over the time course of human
      evolution. We constructed a mathematical model of weight loss under total
      starvation using the established principles of energy balance. Using the model,
      we found that fatter individuals would indeed survive longer and, at a given body
      weight, females would survive longer than males, when totally starved. An allele
      causing deposition of an extra 80 g of fat would result in an extension of life
      under total starvation by about 1.1-1.6% in an individual with 10 kg of fat and
      by 0.25-0.27% in an individual carrying 32 kg of fat. A mutation causing a per
      allele effect of 0.25% would become completely fixed in a population with an
      effective size of 5 million individuals in 6000 selection events. Because there
      have probably been about 24,000 famine events since the evolution of hominins 4
      million years ago, there has been ample time even for genes with only very minor
      impacts on adiposity to move to fixation. The observed polymorphic variation in
      the genes causing the predisposition to obesity is incompatible with the TGH,
      unless all these single nucleotide polymorphisms (SNPs) arose in the last 900,000
      years, a requirement we know is incorrect. The TGH is further weakened by the
      observation of no link between the effect size of these SNPs and their
      prevalence, which would be anticipated under the TGH model of selection if all
      the SNPs had arisen in the last 900,000 years.

PMID- 22864026
TI  - Trypan blue staining of filtering bleb in eyes with operate trabeculectomy.
AB  - OBJECTIVE: To report the use of trypan blue staining of the filtering bleb to
      assess its functional status in eyes undergoing phacoemulsification after
      trabeculectomy. SUBJECTS AND METHODS: This retrospective study was conducted at a
      tertiary eye care centre in North India and studied 33 eyes of 33 patients ( with
      previously operated trabeculectomy), who underwent phacoemulsification. Trypan
      blue dye (0.06%) was used to stain the anterior capsule. After completion of
      phacoemulsification, the staining of the trabeculectomy bleb was noted as
      diffuse, patchy, minimal or no staining. RESULTS: Of the 33 eyes, 13 had diffuse
      staining (39.4%, mean IOP = 9.3 +/- 2.2 mm Hg), 7 (21.2%, mean IOP= 15.5 +/- 1.8
      mm Hg) had patchy staining, 4 had minimal staining (12.1%, mean IOP= 17.5 +/-
      0.5mm Hg) and nine (27.3%, mean IOP= 19.3 +/- 1.6 mm Hg) had no staining. These
      staining patterns were labeled as groups 1 - 4 respectively. Statistical analysis
      showed that the difference between the IOPs in Group 1 - 2 and between Group 2 -
      3 was not significant statistically (p=0.682 and 0.665 respectively). However the
      differences between the IOPs between Groups 1 - 3, 1 - 4, 2 - 4, and 3 - 4 were
      found to be highly significant statistically (p less than 0.0005). CONCLUSIONS:
      Trypan blue dye can be used to test the amount of sub conjunctival filtration in
      eyes undergoing phacoemulsification cataract surgery.

PMID- 22864027
TI  - Efficacy of sutureless and glue free limbal conjunctival autograft for primary
      pterygium surgery.
AB  - INTRODUCTION: There are numerous adjunctive measures described to reduce the
      recurrence rates after pterygium excision. OBJECTIVE: To study the efficacy and
      complications of sutureless and glue free limbal conjunctival autograft for the
      management of primary pterygium over a period of one year. MATERIALS AND METHODS:
      A prospective interventional case series was carried out in 40 consecutive eyes
      with primary nasal pterygium requiring surgical excision. Pterygium excision with
      limbal conjunctival autografting without using glue or sutures was performed in
      all the patients followed by bandaging for 48 hours. The patients were followed
      up post operatively on 2nd day, 1 week, 6 weeks, 6 months and 12 months. They
      were examined for haemorrhage, wound gape, graft shrinkage, chemosis, graft
      dehiscence, recurrence or any other complication. RESULTS: The mean age of the
      patients was 42.8 years (range 23-61), 75% of which were males. Total graft
      dehiscence occurred in 2 eyes (5%), graft retraction in 3 eyes (7.5%) and
      recurrence was seen in 1 eye (2.5%). At 6 weeks postoperatively, the gain in
      uncorrected visual acuity ranged from 0.18 to 0.5 log MAR in 7 eyes. No other
      complication was noted. CONCLUSIONS: Sutureless and glue free limbal conjunctival
      autografting following pterygium excision is a safe, effective and economical
      option for the management of primary pterygium.

PMID- 22864028
TI  - Ganglion cell complex scan in the early prediction of glaucoma.
AB  - OBJECTIVE: To compare the macular ganglion cell complex (GCC) with peripapillary
      retinal fiber layer (RNFL) thickness map in glaucoma suspects and patients.
      SUBJECTS AND METHODS: Forty participants (20 glaucoma suspects and 20 glaucoma
      patients) were enrolled. Macular GCC and RNFL thickness maps were performed in
      both eyes of each participant in the same visit. The sensitivity and specificity
      of a color code less than 5% (red or yellow) for glaucoma diagnosis were
      calculated. Standard Automated Perimetry was performed with the Octopus 3.1.1
      Dynamic 24-2 program. STATISTICS: The statistical analysis was performed with the
      SPSS 10.1 (SPSS Inc. Chicago, IL, EUA). Results were expressed as mean +/-
      standard deviation and a p value of 0.05 or less was considered significant.
      RESULTS: Provide absolute numbers of these findings with their units of
      measurement. There was a statistically significant difference in average RNFL
      thickness (p=0.004), superior RNFL thickness (p=0.006), inferior RNFL thickness
      (p=0.0005) and average GCC (p=0.03) between the suspects and glaucoma patients.
      There was no difference in optic disc area (p=0.35) and vertical cup/disc ratio
      (p=0.234) in both groups. While 38% eyes had an abnormal GCC and 13% had an
      abnormal RNFL thickness in the glaucoma suspect group, 98% had an abnormal GCC
      and 90% had an abnormal RNFL thickness in the glaucoma group. CONCLUSION: The
      ability to diagnose glaucoma with macular GCC thickness is comparable to that
      with peripapillary RNFL thickness . Macular GCC thickness measurements may be a
      good alternative or a complementary measurement to RNFL thickness assessment in
      the clinical evaluation of glaucoma.

PMID- 22864030
TI  - Phacoemulsification surgery by a nationally-trained cataract surgeon of Nepal.
AB  - INTRODUCTION: A one month phacoemulsification training course had been
      implemented by the Nepal Netra Jyoti Sangh (NNJS) in collaboration with
      Association for Ophthalmic Cooperation to Asia, Japan (AOCA). OBJECTIVE: To
      evaluate the visual outcomes of phacoemulsification surgery by a nationally
      trained surgeon in Nepal. MATERIALS AND METHODS: A retrospective study of
      patients that underwent phacoemulsification with foldable intraocular lens
      implantation during a period of 18 months was carried out. Cases that had a six
      week follow-up period were included. Effective phaco time (EPT), intra-operative
      and postoperative complications were noted. Uncorrected visual acuity (UCVA) at
      day 1 and best corrected visual acuity (BCVA) at week 6 were noted. The data were
      analyzed using SPSS 11.5. RESULTS: A total of172 patients that had completed a 6
      week follow-up evaluation were included in the study. The mean age of patients
      was 57.12+/-10.19 years. The mean effective phaco time (EPT) was 9.74+/-7.41
      seconds. Posterior capsule rupture (PCR) with vitreous loss occurred in 2 eyes
      (1.2%), Descemet's membrane detachment in 1 eye (0.6%), capsulorhexis extension
      in 1 eye (0.6%) and wound site thermal injury (WSTI) occurred in 3 eyes (1.7%).
      Postoperative complications were mild to moderate striate keratopathy (9/ 172),
      corneal edema (1/172), corneal epithelial defect (1/172) and uveitis (1/172). At
      6 weeks post-operatively, 165 eyes (95.9%) had a BCVA better than 6/18 and 7 eyes
      (4.1%) had a BCVA of 6/18 to 6/60. CONCLUSION: Patients undergoing
      phacoemulsification had a good visual outcome as a result of the procedure
      performed by cataract surgeon trained from AOCA/NNJS national phacoemulsification
      training program of Nepal.

PMID- 22864029
TI  - Outcome of conjunctival autograft transplantation in pterygium surgery in a
      community based hospital in Nepal.
AB  - INTRODUCTION: The mainstay of treatment for pterygium is surgical excision with
      or without a graft. The most common problem with this intervention is recurrence,
      for which a multitude of factors have been described. OBJECTIVE: To evaluate the
      recurrence rate of pterygium in conjunctival autologous graft transplantation
      after its excision in people living in a hilly region of Nepal Materials and
      methods: A prospective interventional study was conducted in patients undergoing
      pterygium excision with conjunctival autologous graft transplantation. The
      patients were followed up for 20 months. Any recurrence of pterygium was noted
      during this period. RESULTS: Thirty four patients with an age range of 29 to 65
      years (mean 43.88+/-9.19 years) were included. Female predominated (n=21, 61.8%)
      in the study. Service holders formed a majority of the cases (n=14, 41.2%)
      followed by farmers (n=10, 29.4%, OR 0.019, 95% CI = 0.002 to 0.209). Ocular
      discomfort was the main presenting complaint. Dry eye was seen in 30 patients
      (88.23%). Most of the patients (26, 76.5%) had a grade II pterygium. Graft
      displacement was the main complication in two (5.88%) patients and recurrence of
      pterygium was found in three (8.82%). CONCLUSION: Conjunctival autologous
      transplantation is a safe and effective method for the treatment of pterygium
      with a minimal recurrence rate.

PMID- 22864031
TI  - Changing trends in idiopathic retinal vasculitis in a tertiary eye care centre of
      Nepal over a ten-year period.
AB  - OBJECTIVES: To study the demographic profile, clinical presentations, management
      and visual outcome of retinal vasculitis in a tertiary eye care center of Nepal
      MATERIALS AND METHODS: A retrospective, record based study of retinal vasculitis
      cases in the retina clinic of a tertiary care centre in Nepal from January 2009
      to January 2011 was carried out. Results of the study were compared to those from
      the study conducted in a similar set- up between 1998 and 2000. RESULTS: Sixty
      nine eyes of 51 affected patients were evaluated in the study. The male/female
      ratio was 2.64:1 vs 19:1 a decade ago (p=0.0027). The mean age of the patients
      was 33.53 +/- 12.29 years in the present study. Bilateral ocular involvement was
      present in 18 cases (35.3%) vs 56.14% in the past decade (p=0044).The common
      symptoms were dimness of vision (29.4%), floaters (25.5 %) and flashes of light
      (3.92%). Seventy-one eyes (69.6%) had the best corrected visual acuity of 6/18 or
      better. Four eyes (3.92 %) had no light perception. Vascular sheathing was the
      most common finding (32.35%), followed by vitritis (30.39%). Corticosteroids were
      primarily used to manage retinal vasculitis (39.21%). No association of retinal
      vasculitis with tuberculosis was found. CONCLUSION: The demographic pattern and
      clinical presentation of idiopathic retinal vasculitis has changed over a decade
      period in Nepal.

PMID- 22864032
TI  - Visual outcome in open globe injuries.
AB  - OBJECTIVE: To determine the factors affecting the visual outcome in patients with
      open globe injuries of eye. MATERIALS AND METHODS: In a prospective
      interventional study of consecutive patients with open globe injuries, the age,
      gender, place of injury, object causing injury and safety precautions taken were
      recorded. A detailed examination of the eye was done with a slit-lamp. X-rays of
      the orbits were taken in order to determine the presence of a foreign body. The
      injuries were classified as simple or complicated depending on the involvement of
      the pupil/iris, lens and retina. Finally, post operative best-corrected visual
      acuity at last follow up was noted. RESULTS: Fifty-two patients (52 eyes) were
      included in the study. The mean age of patients was 27.25+/-12.62 years (range 9
      73 years). The majority of injuries occurred in the workplace (36.5%); nail
      (15.4%) and glass (15.4%) were the most common objects causing injury. Of those
      with good initial visual acuity, 90% maintained good visual outcome. Patients
      with corneal lacerations of less than 5 mm had significant good visual outcome.
      The number of corneal lacerations and visual axis involvement did not affect the
      visual outcome. Those with corneoscleral lacerations had significantly poor
      visual outcomes compared to those with corneal or scleral lacerations alone.
      CONCLUSION: Predictors of good visual outcome are good initial visual acuity, a
      corneal laceration wound of less than 5mm, a deep anterior chamber, and simple
      lacerations. Age, gender, place of injury, object causing injury, presence of
      hyphema or intraocular foreign body, and the use of safety precautions did not
      affect the visual outcome.

PMID- 22864033
TI  - Expression of oxidative stress in metastatic retinoblastoma- a comparative study.
AB  - OBJECTIVE: To compare oxidative stress between primary retinoblastoma and
      retinoblastoma with distant metastasis. PATIENTS AND METHODS: Forty consecutive
      patients presented with primary retinoblastoma and the same number of patients
      presented with distant metastasis, attending the outpatient department of our
      hospital between August 2002 and April 2005. All the patients with retinoblastoma
      underwent a standard metastasis workup and were subsequently categorized into two
      groups (without metastasis and with metastasis).Venous blood samples were drawn
      from each patient. After proper centrifugation, serum was collected and
      antioxidant enzymes and reactive oxygen species (ROS) were assayed. MAIN OUTCOME
      MEASURES: Serum collected from the patients was subjected to biochemical assay of
      the antioxidant enzymes (superoxide dismutase, catalase and peroxidise) and ROS
      to determine any difference in enzyme activity between the two groups. RESULTS:
      Antioxidant levels were found to be less in the metastasis group as compared to
      the primary intraocular retinoblastoma group(p less than 0.05).Mean ROS activity
      was found to be increased in metastatic group (p less than 0.05). CONCLUSION: The
      decreased antioxidant enzymes level along with increased ROS activity in patients
      with metastatic retinoblastoma reflect increased oxidative stress as compared to
      primary intraocular retinoblastoma patients.

PMID- 22864035
TI  - Prevalence of blindness and visual impairment and its causes among people aged 50
      years and above in Karnali Zone, Nepal.
AB  - OBJECTIVE: To estimate the prevalence of blindness and visual impairment and its
      causes among those aged 50 years and above in Karnali Zone. MATERIALS AND
      METHODS: Stratified cluster sampling method was used. Twenty four clusters of 50
      people aged 50 years and above were selected for the study. Visual acuity was
      recorded with simplified vision testing card with one optotype "E" of size 60 on
      one side and size 18 on the other side. Examination by ophthalmologist under
      mydriasis was done for those with a pinhole visual acuity of less than 6/18.
      RESULTS: Of 1200 enumerated persons 1,174 were examined (97.8% response rate).
      The prevalence of blindness (VA less than 3/60 in better eye) with available
      correction was 3.4% (40), (95% CI=2.36-4.44); 2.3% (15) for male and 4.8% (25)
      for female; with best correction it was 1.6% (19), (95% CI=0.9-2.34), 1.1% (7)
      for male and 2.3% (12) for female. Untreated cataract was the cause of blindness
      in 67.5%. Severe visual impairment (less than 6/60 - 3/60 BCVA in better eye) was
      seen in 2.1% (1.1% male and 3.4% female). Refractive error was the cause of
      visual impairment in 36.8% and untreated cataract in 58.8%. CONCLUSION: Cataract
      and refractive error are the commonest cause of blindness and visual impairment.
      Females are 3 times more prone to blindness than their male counterpart.
      Accessible and equitable services are necessary for blindness prevention.

PMID- 22864034
TI  - Gender equity in eye health of Nepal: a hospital-based study.
AB  - INTRODUCTION: There is a lack of literature examining the impact of gender on
      access to eye care in developing countries. OBJECTIVE: To assess the differences
      in access to eye care between females and males, in the urban hospital setting
      and in rural outreach clinics. MATERIALS AND METHODS: A retrospective study was
      designed to review the patients who sought eye care at a tertiary level eye care
      institute and its rural outreach clinics from 2006 to 2009 in Nepal. Data were
      retrieved from clinical records. RESULTS: In the hospital, females accounted for
      50.8% of patients receiving outpatient care and 48.3% of patients receiving
      surgical care. In rural outreach clinics, females accounted for 56.1% of clinic
      patients and 51.5% of patients undergoing surgery. Fewer girls than boys aged 0
      14 years (44.3%) sought clinical care at the hospital. CONCLUSION: Females
      account for approximately half of the hospital eye care services in Nepal. More
      females seek care at rural outreach clinics than at the urban hospital. However,
      given the female burden of disease in Nepal, there is still much improvement to
      be made in this area of care.

PMID- 22864036
TI  - Hemodynamic effects of intraocular epinephrine during cataract surgery: a double
      blinded placebo controlled randomized clinical trial.
AB  - OBJECTIVE: To evaluate hemodynamic effects of intraocular epinephrine irrigation
      in patients undergoing cataract surgery. MATERIALS AND METHODS: This study was
      conducted as a prospective double blinded clinical trial at the Shahid Sadoughi
      University of Medical Sciences, Yazd, Iran. Eighty-eight patients of age 38-90
      years undergoing were randomly allocated into two groups: Group E received
      intraocular irrigation fluid (balanced salt solution) with epinephrine 1:1000,
      000, and group C received intraocular irrigation fluid (balanced salt solution)
      without epinephrine. Heart rate (HR), systolic and diastolic blood pressure (SBP,
      DBP) were measured before and at 5, 10, 15 minutes after starting intraocular
      infusion of epinephrine1:1000, 000 in both groups. RESULTS: HR and SBP were
      similar in the two groups at different time intervals. DBP was decreased at 5
      minutes after epinephrine administration in the epinephrine group and increased
      at 10 and 15 minutes but there was no significant differences between the two
      groups. CONCLUSION: Intraocular infusion of epinephrine 1:1,000,000 can be used
      during cataract surgery without hemodynamic side effects and so is a safe and
      effective method for this purpose.

PMID- 22864037
TI  - Artificial drainage devices for glaucoma surgery: an overview.
AB  - Artificial drainage devices (ADD) create an alternative pathway for aqueous
      drainage from the anterior chamber of an eye through a tube to the
      subconjunctival bleb connected to an equatorial plate under the conjunctiva. The
      ADDs, both valved and non-valved, are available for end stage or refractory
      glaucoma. Currently, some of these devices, particularly the Express shunt, are
      recommended for the primary treatment of glaucoma. In this article, we highlight
      various ADDs, their indications and contraindications, surgical techniques and
      associated complications.

PMID- 22864038
TI  - Vision science literature of Nepal in the database "Web of Science".
AB  - INTRODUCTION: Vision Science is considered to be a quite developed discipline in
      Nepal, with much research currently in progress. Though the results of these
      endeavors are published in scientific journals, formal citation analyses have not
      been performed on works contributed by Nepalese vision scientists. OBJECTIVE: To
      study Nepal's contribution to vision science literature in the database "Web of
      Science". MATERIALS AND METHODS: The primary data source of this paper was Web of
      Science, a citation database of Thomas Reuters. All bibliometric analyses were
      performed with the help of Web of Science analysis service. RESULTS: In the
      current database of vision science literature, Nepalese authors contributed 112
      publications to Web of Science, 95 of which were original articles. Pokharel GP
      had the highest number of citations among contributing authors of Nepal. Hennig A
      contributed the highest number of article as a first author. The Nepal Eye
      Hospital contributed the highest number of articles as an institution to the
      field of Vision Science. CONCLUSION: Currently, only two journals from Nepal
      including Journal of Nepal Medical Association (JAMA) are indexed in the Web of
      Science database (Sieving, 2012). To evaluate the total productivity of vision
      science literature from Nepal, total publication counts from national journals
      and articles indexed in other databases such as PubMed and Scopus must also be
      considered.

PMID- 22864039
TI  - Repositioning of Ahmed glaucoma valve tube in the anterior chamber with prolene
      sutures to manage tube-endothelial touch.
AB  - BACKGROUND: Corneal endothelial damage is a known complication of aqueous shunt
      surgery. OBJECTIVE: To describe a new technique for repositioning the Ahmed
      glaucoma valve tube in a case of tube-endothelial touch. CASE: A patient with
      advanced glaucoma, having undergone Ahmed glaucoma valve (AVG) implantation,
      developed localized corneal endothelial damage due to contact between the tube
      and superior corneal endothelium. Two 10-0 prolene anchor sutures were passed
      over the tube in the anterior chamber, repositioning it away from the
      endothelium, thus preventing further damage to the corneal endothelium.
      Resolution of corneal oedema was noted without affecting the tube drainage and
      intraocular pressure. CONCLUSION: Intracameral repositioning of the shunt tube
      using prolene sutures is a useful technique for correcting the tube malposition.

PMID- 22864040
TI  - Prosthetic rehabilitation of a patient with enucleated eye - a case report.
AB  - BACKGROUND: The loss of an eye has a crippling effect on the psychology of the
      patient, making rehabilitation process challenging for both doctor and patient.
      OBJECTIVE: To report a case of anophthalmic socket with prosthetic rehabilitation
      in a cost effective manner. CASE: A 32-year-old female presented with
      anophthalmic socket for prosthetic rehabilitation. A custom made ocular
      prosthesis was implanted successfully. CONCLUSION: The custom made ocular
      prosthesis is simple, affordable and can be carried out in a small clinical set
      up and provides a superior natural appearance.

PMID- 22864041
TI  - Ocular myocysticercosis: favorable outcomes with early diagnosis and appropriate
      therapy.
AB  - BACKGROUND: Ocular myocysticercosis is rare and a high index of suspicion is
      required for its diagnosis. OBJECTIVE: To describe clinical characteristics and
      treatment outcome of ocular myocysticercosis. CASES: We describe a series of
      three patients who had different clinical presentations of ocular
      myocysticerocosis namely diplopia, restricted ocular motility and sub
      conjunctival cyst. The treatment with oral albendazole and prednisolone was
      effective in all three cases. CONCLUSION: Favorable outcomes can be achieved with
      a high index of suspicion, early diagnosis and treatment with oral albendazole
      and prednisolone in patients with ocular myocysticercosis.

PMID- 22864042
TI  - Accommodative spasm with bilateral vision loss due to untreated intermittent
      exotropia in an adult.
AB  - BACKGROUND: Intermittent exotropia (IXT) is an exodeviation intermittently
      controlled by fusional mechanisms. Patients with IXT may present with asthenopic
      symptoms, blurred vision, headaches, diplopia or visual confusion and reading
      difficulties; especially after prolonged periods of near work. OBJECTIVE: To
      report the presentation and management of a young adult with intractable
      accommodative spasm secondary to long standing intermittent exotropia. CASE: The
      patient was found to have bilateral accommodative spasm with high pseudomyopia
      and severe impairment of vision. There was a tendency for recurrence with
      discontinuation of cycloplegics. CONCLUSION: A total relief of symptoms was
      noticed after strabismus surgery was undertaken for the exotropia. A detailed
      orthoptic evaluation with emphasis on recognizing accommodative spasm as an
      unusual presentation of IXT, could aid in appropriate diagnosis and treatment of
      such cases.

PMID- 22864043
TI  - Melanocytoma of the optic disc - a case report.
AB  - INTRODUCTION: Melanocytoma of the optic disc is a benign lesion. OBJECTIVE: To
      describe a case of optic disc melanocytoma CASE: A 48-year old lady presented
      with gradual visual impairment associated with a floater. The right eye fundus
      examination showed a mass uniformly dark black in colour on the optic disc. The
      mass completely obscured the fluorescence on fluorescein angiography and was thus
      differentiated from malignant melanoma. CONCLUSION: Optic disc melanocytoma can
      present with visual impairment and a floater. Fluorescein angiography can be
      useful to differentiate between malignant melanoma and melanocytoma.

PMID- 22864044
TI  - Homocystinuria masquerading as vitamin B12 deficiency.
AB  - BACKGROUND: Homocystinuria is a rare metabolic disorder characterized by excess
      homocysteine in the urine. Vitamin B12 deficiency has diverse cutaneous, nervous
      and ophthalmic manifestations. OBJECTIVE: To report a case of homocystinuria
      masquerading as vitamin B 12 deficiency. CASE: We hereby are presenting an
      interesting case of a 4 year old boy who was being treated for Vitamin B 12
      deficiency on the basis of history of delayed milestone, abdominal pain and
      hyperpigmentation of skin which was diagnosed as homocystinuria. CONCLUSION: It
      is important to carry out ophthalmological examination in every case of
      megaloblastic anemia if associated with blurring of vision and mental
      retardation.

PMID- 22864045
TI  - Malignant transformation of kissing nevus- a rare entity.
AB  - BACKGROUND: Kissing nevus is a congenital nevus in adjacent parts of the eyelids.
      Malignant transformation of kissing or divided nevi of the eyelids is rarely
      described. OBJECTIVE: To report a very rare case of malignant transformation of
      kissing nevus with ocular and extraocular spread. CASE: A 57- year- old man with
      6/6 visual acuity in both eyes presented with a kissing nevus present since birth
      in right upper and lower eyelids which had a slow growth phase. The upper lid in
      the area of the nevus was thickened with a 20x12x15 mm black pigmented crusted
      hemorrhagic nodular lesions. The lower lid had a 6 mm black pigmented ulcerated
      lesion over the pre-existing nevus in the lateral third of the lid with full
      thickness infiltration. Another 5x4 mm pigmented lesion over the lower medial lid
      margin with a thickness of about 3 mm extended to the conjunctival side of the
      lower lid. Right sided pre-auricular and sub-maxillary nodes were palpable. A
      biopsy of tissue samples from the eyelid and pre-auricular nodes were consistent
      with malignant melanoma. CONCLUSION: Malignant transformation of kissing nevus is
      rare. It can spread to the conjunctiva,pre-auricular and sub-mandibular
      lymphnodes.

PMID- 22864046
TI  - An unusual case of transient cortical blindness with sagittal sinus thrombosis in
      a case of Henoch-Schonlein purpura.
AB  - INTRODUCTION: Henoch-Schonlein purpura (HSP) is one of the most common causes of
      small vessel vasculitis in children, but sometimes may have an atypical
      presentation. OBJECTIVE: To report an unusual case of transient cortical
      blindness in a patient with Henoch-Schonlein purpura. CASE: A 3-year-old female
      child was brought with the complaint of diffuse abdominal pain and hematochezia,
      which was preceded by high grade fever and cough. Three days later she developed
      hematuria, hematemesis, melena and hemoptysis along with palpable purpura. Four
      days later she became irritable and developed a few episodes of generalized tonic
      clonic seizure, followed by cortical blindness. The CT scan of the brain showed
      bilateral non-enhancing occipital hypodensity. The magnetic resonance venography
      showed thrombosis in transverse and sigmoid sinus. She was treated with
      corticosteroids and her mental status and vision improved. CONCLUSION: The HSP
      can cause transient cortical blindness, and recovery is good if therapy is
      initiated at the appropriate time.

PMID- 22864047
TI  - Weill- Marchesani syndrome: a rare case report.
AB  - OBJECTIVE: To describe the presenting features of Weill-Marchesani syndrome CASE:
      A 22-year-old man presented with high myopia and progressive visual disturbance.
      He was of short stature and had brachydactyly. His initial Snellen best corrected
      visual acuity (BCVA) was 6/24 in his right eye and 6/12 in his left eye. Slit
      lamp examination revealed a sub-luxated micro-spherophakic lens. The patient was
      diagnosed with Weill-Marchesani syndrome. CONCLUSION: Weill-Marchesani syndrome
      can present wwith progressive myopia in a person of short stature and
      brachydactyly.

PMID- 22864048
TI  - Choroidal metastases as the sole initial presentation of metastatic lung cancer:
      case report and review of literature.
AB  - BACKGROUND: Choroidal metastasis as an initial presenting feature of metastatic
      lung cancer is exceedingly rare. External beam radiotherapy (EBRT) is an
      effective and widely accepted therapeutic modality. However, data addressing the
      effectiveness of other treatment strategies is limited. Herein, we present a
      patient with choroidal metastases secondary to lung cancer and review the
      relevant literature. CASE REPORT: A 25-year-old male presented with deterioration
      of vision. His evaluation revealed bilateral choroidal metastasis secondary to
      adenocarcinoma of the lung. Unfortunately, his vision continued to deteriorate
      despite treatment with EBRT and chemotherapy. CONCLUSION: Metastatic lung cancer
      can manifest with choroidal metastasis as an initial presentation.

PMID- 22864049
TI  - Surgically induced astigmatism of small incision cataract surgery.

PMID- 22864050
TI  - Trench, lollipop, lift and chop technique for mild to moderate cataracts.

PMID- 22864051
TI  - Patient reported evaluation of functional symptoms (PREFS): a simple method of
      ascertaining patient satisfaction post cataract surgery.

PMID- 22864052
TI  - How should the ophthalmologists treat the methanol-induced toxic optic
      neuropathy?

PMID- 22864053
TI  - Ten year survival of bridges placed in the General Dental Services in England and
      Wales.
AB  - AIM: It is the aim of this paper to consider the factors associated with the need
      for re-intervention on a conventional or resin-retained bridge, excluding
      recementation. METHODS: A data set was established consisting of patients, 18
      years or older, whose birthdays were included within a set of randomly selected
      dates, one of which was chosen in each possible year of birth and whose
      restoration records contained the placement of one or more indirect restorations
      on courses of treatment with last date on the claim form after 31st December
      1990, and with date of acceptance after September 1990 and before January 2002.
      For each patient treated with a bridge, the subsequent history of intervention on
      each tooth used as a bridge abutment was consulted, and the next date of
      intervention, if any could be found in the extended data set, was obtained. Thus
      a data set was created of bridge abutments which have been placed, with their
      dates of placement and their dates, if any, of re-intervention. RESULTS: Data for
      over 80,000 different adult patients were analysed, of whom 46% were male and 54%
      female. A total of 7874 abutments (6800 conventional and 1074 resin-retained)
      were obtained from the data over a period of eleven years. Factors which were
      found to reduce outcome of bridges included type of bridge, patient payment
      exemption status, patient attendance pattern and position of the bridge in the
      patient's mouth. CONCLUSIONS: Survival of conventional bridge abutments has been
      shown to be 72% at 10 years, this being similar survival time to crowns. Various
      patient factors and bridge type were also found to influence survival.

PMID- 22864054
TI  - Ring expansion of alkynyl cyclopropanes to highly substituted cyclobutenes via a
      N-sulfonyl-1,2,3-triazole intermediate.
AB  - Regioselective ring expansion of alkynyl cyclopropanes to highly substituted
      cyclobutenes was developed. The reaction involves a copper-catalyzed
      cycloaddition of an alkyne with an arylsulfonyl azide and a silver-catalyzed
      carbene formation followed by ring expansion of a cyclopropyl carbene
      intermediate.

PMID- 22864056
TI  - Peanut consumption increases levels of plasma very long chain fatty acids in
      humans.
AB  - Peanut consumption has been suspected of raising plasma very long chain fatty
      acid (VLCFA) levels in humans. The effect of peanut consumption on VLCFAs was
      studied in six human subjects. After 3 to 4h of peanut butter ingestion, plasma
      C26:0 and C26:0/C22:0 were found to be significantly elevated to levels seen in
      patients with peroxisomal disorders. These levels returned to normal within 12h.
      Peanut consumption needs to be accounted for when interpreting VLCFAs.

PMID- 22864057
TI  - Current diagnosis and management of mucopolysaccharidosis VI in the Asia-Pacific
      region.
AB  - INTRODUCTION: Mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) is a
      clinically heterogeneous lysosomal storage disorder. It presents significant
      diagnostic and treatment challenges due to the rarity of the disease and
      complexity of the phenotype. As information about MPS VI in Asia-Pacific
      countries is limited, a survey was conducted to assess current practices for
      diagnosis and management of MPS VI in this region. The participants were selected
      based on their experience in diagnosing and managing MPS patients. METHODS: The
      survey comprised 29 structured quantitative or qualitative questions. Follow-up
      consultations were undertaken to discuss the data further. RESULTS: Thirteen
      physicians from eight countries or regions (Australia, China, Hong Kong, Japan,
      Malaysia, Philippines, Taiwan and Thailand) were surveyed. At the time of the
      survey twenty-two patients with MPS VI were directly treated by the respondents
      and most (~80%) had rapidly progressing disease. A wide range of medical
      specialists are involved in managing patients with MPS VI, the most common being
      orthopedic surgeons, pediatricians and geneticists. The
      availability/accessibility of diagnostic tools, therapies and national insurance
      coverage vary greatly across the countries/regions and, in some cases, between
      different regions within the same country. Currently, there are national MPS
      management groups in Australia and Japan. Australia, Taiwan and Hong Kong have
      local guidelines for managing MPS and local MPS registries are available in
      Australia, Taiwan, and Japan. CONCLUSIONS: This survey highlights differences in
      the diagnosis and management of MPS VI between Asia-Pacific countries/regions.
      Important barriers to advancing the identification, understanding and treatment
      of MPS VI include the paucity of epidemiological information, limited access to
      laboratory diagnostics and therapies, low disease awareness, and a lack of
      monitoring and treatment guidelines. There is a clear need to facilitate
      communications between physicians and establish regional or national disease
      registries, a multidisciplinary referral network, and a centralized diagnostic
      and management framework.

PMID- 22864058
TI  - Pathological and epidemiological factors associated with advanced stage at
      diagnosis of breast cancer.
AB  - BACKGROUND: Breast cancer is a highly heterogeneous disease, but the stage at
      presentation significantly influences outcome. It is important to dissect the
      pathobiological and epidemiological factors that influence the stage at
      presentation in order to develop effective strategies to improve clinical
      outcome. SOURCES OF DATA: PubMed references relating to breast cancer subtypes,
      molecular classification of breast cancer, genetic susceptibility, young women
      and breast cancer. AREAS OF AGREEMENT: HER-2 positive, basal-like tumours and
      inflammatory breast cancers (IBC) more frequently present as late stage disease.
      Socioeconomic, cultural and ethnic background also influence stage at
      presentation. AREAS OF CONTROVERSY: The biology of IBC is poorly understood.
      Relative contribution of social and genetic factors in certain ethnic groups.
      GROWING POINTS Molecular determinants of breast cancer behaviour. Genetic and
      biological factors influencing disease phenotype in different ethnic groups.
      AREAS TIMELY FOR DEVELOPING RESEARCH: Biology of basal-like tumours and IBC. Role
      of predisposition of genetic variants in determining breast cancer phenotypes.
      Biological differences in breast cancer from different ethnic groups.

PMID- 22864055
TI  - Macrophage paraoxonase 2 regulates calcium homeostasis and cell survival under
      endoplasmic reticulum stress conditions and is sufficient to prevent the
      development of aggravated atherosclerosis in paraoxonase 2 deficiency/apoE-/-
      mice on a Western diet.
AB  - Paraoxonase 2 deficiency (PON2-def) alters mitochondrial function and exacerbates
      the development of atherosclerosis in mice. PON2 overexpression protects against
      ER stress in cell culture. In this paper, we examined the role of PON2 in the
      unexplored link between ER stress and mitochondrial dysfunction and tested
      whether restoration of PON2 in macrophages is sufficient to reduce aggravated
      atherosclerosis in PON2-def/apoE(-/-) mice on a Western diet. ER stress response
      genes, intracellular calcium levels, and apoptotic nuclei were significantly
      elevated in PON2-def/apoE(-/-) macrophages compared to apoE(-/-) macrophages in
      response to ER stressors, but not at the basal level. In contrast, PON2-def/apoE(
      /-) macrophages exhibited greater mitochondrial stress at the basal level, which
      was further worsened in response to ER stressors. There was no difference in ER
      stress response genes and apoptotic nuclei between apoE(-/-) and PON2-def/apoE(-/
      ) macrophages when pretreated with xestospongin (which blocks the release of
      calcium from ER) suggesting that PON2 modulates cell survival and ER stress by
      maintaining calcium homeostasis. Treatment with a mitochondrial calcium uptake
      inhibitor, RU360, attenuated ER stressor mediated mitochondrial dysfunction in
      PON2-def/apoE(-/-) macrophages. CHOP expression (ER stress marker) and apoptotic
      nuclei were significantly higher in aortic lesions of PON2-def/apoE(-/-) mice
      compared to apoE(-/-) mice fed a Western diet. Restoration of PON2 in macrophages
      reduced ER stress, mitochondrial dysfunction and apoptosis in response to ER
      stressors. Furthermore, restoration of PON2 in macrophages reduced lesional
      apoptosis and atherosclerosis in PON2-def/apoE(-/-) mice on a Western diet. Our
      data suggest that macrophage PON2 modulates mechanisms that link ER stress,
      mitochondrial dysfunction and the development of atherosclerosis.

PMID- 22864059
TI  - Interactive web-based breastfeeding monitoring: feasibility, usability, and
      acceptability.
AB  - BACKGROUND: Strategies that promote higher exclusive breastfeeding rate and
      duration are highly recommended. To date, no study has tested the feasibility of
      Web-based monitoring among breastfeeding mothers. GOALS: To develop an
      interactive Web-based breastfeeding monitoring system (LACTOR) and examine its
      feasibility, usability, and acceptability among breastfeeding mothers. METHODS: A
      prospective, descriptive, mixed-methods study was conducted. Mothers who met the
      study inclusion criteria were recruited from mother infant units in 2 Midwestern
      hospitals in the United States. Mothers were asked to enter their breastfeeding
      data daily through the system for 30 days and then submit an online exit survey.
      This survey consisted of a system usability scale and mothers' perceptions form.
      Twenty-six mother/infant dyads completed the study. RESULTS: The Feasibility of
      LACTOR was established by mothers' compliance in entering their breastfeeding
      data. The mean was 8.87 (SD = 1.21) daily entries, and the range was 6-13 times
      per day. Usability scale total mean score was 3.35 (SD = 0.33; scale range 0-4).
      Ninety-two percent of the mothers thought that they did not need to learn many
      skills before they started to use LACTOR and did not need any technical support.
      Mothers reported that the monitoring was beneficial and gave them the chance to
      track their infants' feeding patterns and detect any problems early. CONCLUSIONS:
      This study demonstrated the feasibility of LACTOR, and it was user-friendly and
      acceptable among mothers. Further studies to test its effect on breastfeeding
      outcomes are needed.

PMID- 22864060
TI  - Enhanced expression of organic anion transporting polypeptides (OATPs) in
      androgen receptor-positive prostate cancer cells: possible role of OATP1A2 in
      adaptive cell growth under androgen-depleted conditions.
AB  - The biological mechanisms underlying castration resistance of prostate cancer are
      not fully understood. In the present study, we examined the role of organic anion
      transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate
      (DHEAS) into cells to support growth under androgen-depleted conditions. Cell
      growth and mRNA expression of OATP genes were studied in human prostate cancer
      LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect
      of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been
      silenced. Growth of both cell lines was stimulated by DHEAS and the effect was
      attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to
      DHEA. OATP1A2 mRNA expression was increased most prominently among various genes
      tested in LNCaP cells grown in androgen-depleted medium. Similar results were
      obtained with 22Rv1 cells. Furthermore, the characteristics of [(3)H]DHEAS uptake
      by LNCaP cells were consistent with those of OATP-mediated transport. Knockdown
      of OATP1A2 in LNCaP cells resulted in loss of the DHEAS sensitivity of cell
      growth. Our results suggest that enhanced OATP1A2 expression is associated with
      adaptive cell growth of prostate cancer cells under androgen-depleted conditions.
      Thus, OATP1A2 may be a pharmacological target for prostate cancer treatment.

PMID- 22864061
TI  - Sildenafil stimulates the expression of gaseous monoxide-generating enzymes in
      vascular smooth muscle cells via distinct signaling pathways.
AB  - Sildenafil is a cGMP-specific phosphodiesterase type 5 inhibitor that augments
      cGMP accumulation following the activation of soluble guanylate cyclase (sGC). In
      this study, we investigated whether sildenafil promotes the production of the sGC
      stimulatory gases, carbon monoxide and nitric oxide, by stimulating the
      expression of the inducible isoforms of heme oxygenase (HO-1) and nitric oxide
      synthase (iNOS) in vascular smooth muscle cells (SMCs). Sildenafil increased HO-1
      expression and potentiated cytokine-mediated expression of iNOS and NO synthesis
      by SMCs. The induction of HO-1 was unaffected by the sGC inhibitor 1H
      (1,2,4)oxadiazolo[4,3-alpha]quinozalin-1-one (ODQ) or the protein kinase G
      inhibitor (8R,9S,11S)-(-)-2-methyl-9-methoxyl-9-methoxycarbonyl-8-methyl-2,3,9,10
      tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cyclocta9(cde)trinen-1
      one (KT 5823). However, the sildenafil-mediated increase in HO-1 promoter
      activity was abolished by mutating the antioxidant responsive elements in the
      promoter or by overexpressing a dominant-negative mutant of NF-E2-related factor
      2 (Nrf2). Furthermore, the induction of HO-1 by sildenafil was accompanied by an
      increase in reactive oxygen species (ROS) and blocked by N-acetyl-L-cysteine and
      rotenone. In contrast, the enhancement of cytokine-stimulated NO synthesis by
      sildenafil was prevented by ODQ and the protein kinase A inhibitor (9S,10S,12R)
      2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo(1,2,3
      fg:3',2',1'-kl)pyrrolo(3,4-i)(1,6)benzodiazocine-10-carboxylic acid hexyl ester
      (KT 5720) and duplicated by lipophilic analogs of cGMP. In conclusion, these
      studies demonstrate that sildenafil stimulates the expression of HO-1 and iNOS
      via the ROS-Nrf2 and sGC-cGMP pathway, respectively. The ability of sildenafil to
      block the catabolism of cGMP while stimulating the synthesis of sGC-stimulatory
      gaseous monoxides through the induction of HO-1 and iNOS provides a potent
      mechanism by which cGMP-dependent vascular actions of this drug are amplified.

PMID- 22864063
TI  - Accurate preoperative staging of gastric cancer with combined endoscopic
      ultrasonography and PET-CT.
AB  - Accurate staging of gastric cancer is helpful to determine the most appropriate
      therapy, but no staging modality has been accepted as the standard. Objective is
      to evaluate the usefulness of endoscopic ultrasonograph (EUS) combined with
      position emission tomography and computed tomograph (PET-CT) in gastric cancer
      staging. A total of 124 patients confirmed with gastric cancer were subjected to
      staging with EUS and PET-CT scanning. The detection rate of primary tumor was
      99.2% by combination use of two modalities and 97.6% by EUS alone (p = 0.6219),
      but the detection rate was 90.3% (112 of 124) by PET-CT alone (compared with the
      combination, p = 0.0027; compared with EUS alone, p = 0.0299). The locoregional
      lymph node invasion was identified in 84/124 (67.7%) by combined PET-CT and EUS,
      which was obviously higher than that with EUS (52.4%) or PET-CT (43.5%) alone (p
      = 0.0194 and p = 0.0002, respectively). There was no statistical difference in
      identification of celiac axis lymph node metastasis among three methods, but the
      combined examination or PET-CT alone was more effective than EUS alone in the
      detection of distant metastases (all p < 0.01). Furthermore, the combined EUS and
      PET-CT was more optimal than using EUS or PET-CT alone in the accurate T and N
      staging and the effect on change of treatment. The present study indicates that
      the combination of EUS and PET-CT is an ideal modality in the preoperative
      staging of gastric cancer and it provides beneficial guidance for the treatment
      of gastric cancer.

PMID- 22864064
TI  - Healthcare workers in conflict zones- fright or flight?

PMID- 22864062
TI  - Investigation of iterative image reconstruction in three-dimensional optoacoustic
      tomography.
AB  - Iterative image reconstruction algorithms for optoacoustic tomography (OAT), also
      known as photoacoustic tomography, have the ability to improve image quality over
      analytic algorithms due to their ability to incorporate accurate models of the
      imaging physics, instrument response and measurement noise. However, to date,
      there have been few reported attempts to employ advanced iterative image
      reconstruction algorithms for improving image quality in three-dimensional (3D)
      OAT. In this work, we implement and investigate two iterative image
      reconstruction methods for use with a 3D OAT small animal imager: namely a
      penalized least-squares (PLS) method employing a quadratic smoothness penalty and
      a PLS method employing a total variation norm penalty. The reconstruction
      algorithms employ accurate models of the ultrasonic transducer impulse responses.
      Experimental data sets are employed to compare the performances of the iterative
      reconstruction algorithms to that of a 3D filtered backprojection (FBP)
      algorithm. By the use of quantitative measures of image quality, we demonstrate
      that the iterative reconstruction algorithms can mitigate image artifacts and
      preserve spatial resolution more effectively than FBP algorithms. These features
      suggest that the use of advanced image reconstruction algorithms can improve the
      effectiveness of 3D OAT while reducing the amount of data required for biomedical
      applications.

PMID- 22864065
TI  - "Medical humanities" for India.

PMID- 22864066
TI  - Standing committee report on CDSCO: hard facts confirm an open secret.

PMID- 22864068
TI  - The patient-doctor relationship.
AB  - In this essay I speak about the need to put the patient first when discussing the
      relationship between the patient and the doctor. From my own experience of having
      been a cancer patient, I argue that most patients appreciate and feel empowered
      by knowledge about their illness if this knowledge is given sensitively. I also
      try to explain why doctors need to recognise and respond sensitively to the
      patient's need to be healed, psychologically, as well, especially in cases of
      serious or chronic illnesses.

PMID- 22864067
TI  - Syria: public health achievements and the effect of sanctions.

PMID- 22864069
TI  - My recent experiences as a patient.
AB  - As a neurosurgeon, it was a new experience for me to face the consequences of an
      accidental fall just before I underwent simple spinal surgery for relief from
      backache. This essay describes how I was affected by the unexpected operations
      that followed. The physical pain, the anxieties, small inconveniences and the
      relatively free use of drugs such as antibiotics, that I might have taken for
      granted in my patients undergoing surgery, now took on a new meaning for me. My
      perspective on my illness as patient, rather than as physician, and the special
      care given to me by medical, nursing, and paramedical colleagues were
      transforming experiences. Based on these occurrences, I offer suggestions on how
      we can improve our approach to patients.

PMID- 22864071
TI  - An undergraduate student's view of the medical humanities.

PMID- 22864072
TI  - Medical humanities: a resident doctor's perspective.
AB  - The barrage of competitive examinations, overwork, sleep deprivation, and the
      pressure of expectations all combine to destroy the dreams that resident doctors
      have when they start medical school. The empathy they had before entering this
      field fades away, and they eventually become insensitive to their patients.  
      Medical humanities may be the means to halt this trend. Sensitising young minds,
      using the arts, literature, history and lessons on social issues, may bring about
      a paradigm shift in these doctors' outlook towards their patients.   However, for
      the humanities to be integrated into medical education, the current curriculum
      must be modified and made more clinically and socially relevant. Further, the
      humanities cannot be taught in lecture halls; they need to be integrated into all
      aspects of medical school. For this, the medical school faculty should be
      sensitised to, and trained in, humanities education.

PMID- 22864073
TI  - Medical humanities ... almost.
AB  - Brought up in the traditional education system in a large teaching hospital in
      Mumbai, India, I moved on to do specialisation in neurology in the United States
      of America. The Indian system of pre-medical education mandates early choices
      between the humanities and the sciences and thus precludes a more well-rounded
      development of a student. Though medical humanities is not taught as a subject as
      part of the medical curriculum in India, listening to inspiring and learned
      teachers and the daily interaction with scores of patients who are willing to
      submit themselves to examination "in the cause of medical education" is a
      humbling experience to a sensitive student. I see similar willingness in patients
      in the United States. However, a formal course in the medical humanities,
      including arts, literature, and philosophy will surely enrich the experience of a
      larger number of undergraduates and postgraduates learning the core subjects and
      help in moulding a more rounded physician.

PMID- 22864074
TI  - Whither medical humanities?
AB  - Understanding the medical humanities (MH) and their role in medical education is
      in its infancy in India. Students are initiated into professional (medical)
      education too early in life, usually at the expense of a basic grounding in the
      humanities, resulting in warped intellectual growth. The author, arguing against
      the wholesale import of foreign systems, advocates free inquiry by medical
      educators to evolve a humanities programme for medical students derived from our
      own cultural context. This essay describes the early experiences of efforts to
      make a beginning at the University College of Medical Sciences, Delhi. The author
      reviews the various strategies used and the challenges of introducing the subject
      to the current generation of medical students.

PMID- 22864075
TI  - Integrating medical education with societal needs.

PMID- 22864076
TI  - Embracing the unknown: introducing medical humanities into the undergraduate
      medical curriculum in India.
AB  - Medical education fails to address the medical student's many questions, doubts
      and anxieties about his profession and his own relation to it. Students' growing
      disillusionment with the profession and increasing disconnect with the realities
      of the healthcare scene in India have reached critical levels, resulting in a
      general clamour for reform of the medical curriculum. Many look towards medical
      humanities for the answer to the problem. Referring to some of the available
      western thinking and practice of medical humanities (MH), this paper recommends
      the evolution of an indigenous model which will draw on the growing body of new
      scholarship on India in the humanities and the social sciences. Some guidelines
      are offered for starting an MH programme, stressing the need for a flexible and
      broad-based approach, and a participatory pedagogy focused on students' needs,
      that draws creatively on available resources. Rather than viewing the 'arts' as a
      discrete addition to our personalities, an MH programme needs to show us how to
      integrate the multiple facets of our personalities.

PMID- 22864077
TI  - Healthcare the Ayurvedic way.
AB  - Ayurveda, the indigenous medical system of India, has integrated the concept of
      interconnectedness into its understanding of health and disease. It considers the
      human body as an indivisible whole with a network of interrelated functions, mind
      and consciousness, wherein a disturbance in one part will have repercussions in
      other parts as well. The key to health is for these factors to maintain stability
      since disease is seen as a perturbation in this network. Ayurvedic treatment aims
      not only at removal of disease, but also at the restoration of the equilibrium of
      bodily functions.    The centuries-old science of Ayurveda, apart from being a
      holistic form of medicine, also clearly defines the student-teacher and doctor
      patient relationship. It sets high ethical standards of professional and personal
      integrity for the doctor, teacher and student. In addition to being technically
      skilled and well-read in the science, practitioners of Ayurveda must be
      compassionate and empathetic. Students of Ayurveda are taught the importance of
      compassionate caring for patients and maintaining personal integrity.

PMID- 22864078
TI  - How 'informed' is informed consent? Findings from a study in South India.
AB  - A qualitative study using in-depth interviews was carried out among patients and
      doctors working in a private hospital in Tamil Nadu, to understand perceptions of
      informed consent. Audio-recorded interviews were transcribed verbatim and a
      framework analytical approach was used in analysis. Emergent themes ranged from
      perceptions on informed consent, and discussing health concerns and decision
      making, to information provided by and expectations from doctors, and suggestions
      for improvement. Most patients were unfamiliar with the kind of information
      provided in the informed consent process; a few felt that the information was
      inadequate. Decision making about surgery was left mostly to the doctor. Poor
      literacy in patients was seen as a barrier to effective communication by doctors.
      Developing local language versions of consent forms supported by audiovisual aids
      is needed for patients to take a proactive role in their treatment process, and
      for doctors to be receptive to patients' needs and capacities.

PMID- 22864079
TI  - Informed consent among nursing students participating in biomedical research.
AB  - For consent in biomedical research, it is essential that research participants
      understand the need for research, the study protocol, the risk and benefits of
      participation, the freedom to participate or decline and the right to leave the
      study at any time. A structured questionnaire was used to assess understanding
      and knowledge among nursing trainees participating in a cohort study
      investigating exposure and latent tuberculosis at a tertiary care hospital. Data
      were collected for 138 participants. While 97% were aware of their enrollment
      into a research protocol, only 78% could state that it was a study on
      tuberculosis. Approximately two-thirds were aware of plans for blood collection,
      but not all of them knew the timings or number of samples. The majority (59%)
      participants had consulted others before making the decision to participate, and
      only 73% felt that their participation was completely voluntary. Even among
      healthcare trainees, emphasis needs to be placed on testing both the knowledge
      and understanding of participants to ensure the principle and practice of truly
      informed consent.

PMID- 22864080
TI  - Patient advocacy practice among Iranian nurses.
AB  - This cross-sectional study among nurses at the hospitals of the Tehran University
      of Medical Sciences aimed to investigate the extent of involvement in patient
      advocacy practice among nurses. Participants (n=330) were selected using
      proportionate systematic random sampling. Data were gathered through patient
      advocacy questionnaires and analysed using descriptive/inferential statistics.
      The average of nurses' patient advocacy practice was 3.848+ 0.304 (possible range
      1-5). One third of the participant nurses had high scores in practising patient
      advocacy, two thirds of them had scores in the medium range and 0.6% of nurses
      had low scores. The majority of nurses (83.5%) declared their commitment to
      patient advocacy as high, and 42.5% believed they had enough ability to practise
      advocacy. Half of the participants claimed to have faced problems following
      advocacy practices. The problems that most participants reported included
      conflict with colleagues and/or superiors, receiving oral/written admonitions,
      and shift and/or ward changes. Patient advocacy scores were significantly higher
      among female nurses, head nurses, and those who had more commitment and ability
      for patient advocacy (p<0.001). In contrast, nurses who worked in more than one
      hospital simultaneously due to financial need (p=0.048), and experienced conflict
      with superiors (p=0.047) scored less than others. The nurses in our study carried
      out advocacy at acceptable levels and adopted it as part of their own
      professional role. Nurses tended to advocate for patients, but they faced many
      challenges in this.

PMID- 22864081
TI  - Some ethical tradeoffs in mental health legislation and practice.
AB  - An examination of the intersection of legal and medical discourses, particularly
      in the realm of mental health legislation, provides a rich opportunity to clarify
      fundamental ethical conflicts. This essay studies one such legal discourse, the
      draft amendments to the Mental Health Act (1987), to demonstrate that the realm
      of ethical decision-making is constrained not only by pragmatic administrative,
      training and financial issues but also by the very contradictions that are
      necessarily at the heart of any ethically conducted project, however well
      intentioned and reasoned.

PMID- 22864082
TI  - Tarnishing reputations: the downside of medical activism.

PMID- 22864083
TI  - Concepts and debates in end-of-life care.
AB  - Debates in India on end-of-life care assumed a new life after the petition in the
      Supreme Court in the case of Aruna Ramchandra Shanbaug, calling for withdrawal of
      life-sustaining therapy from a patient in a persistent vegetative state. The
      Court's landmark decision has led the way for discussing and developing
      guidelines on various situations in end-of- life care. This paper discusses some
      key concepts in end-of-life care - medical futility, palliative care, advance
      directives, surrogate decision making, physician assisted suicide and euthanasia 
      with reference to the guidelines of various medical associations and decisions
      in Indian courts.

PMID- 22864084
TI  - ICMR's ethical guidelines for biomedical research on human participants: need for
      clarification.
AB  - The "Ethical guidelines for biomedical research on human participants" prepared
      by the Indian Council of Medical Research in 2006 came as a welcome step in the
      process of regulation of research on human subjects, since clear cut Indian
      guidelines were absent earlier. The guidelines have been accepted as the standard
      operating manual by Institutional Ethics Committees (IEC) in India. However, over
      a period of time, it has become obvious that the guidelines lack clarity in
      certain areas and require to be revised in the light of experiences of members in
      the IECs. Some of these problems with the ICMR guidelines have been highlighted
      in this paper to press for revision of the manual in the light of these
      experiences.

PMID- 22864085
TI  - Proactive role for ethics committees.

PMID- 22864086
TI  - Privatisation of healthcare and the Left.

PMID- 22864087
TI  - Public health in India: unethical neglect.

PMID- 22864088
TI  - Analysis of physicians' strikes and their impact.

PMID- 22864089
TI  - Human embryonic stem cells: cells without end?

PMID- 22864090
TI  - Ethics of bedside clinics.

PMID- 22864091
TI  - Are doctors soft targets for government?

PMID- 22864092
TI  - Factors affecting learner satisfaction with an internet-based curriculum.
AB  - OBJECTIVE: Online curricula are used increasingly for educating physicians, and
      evaluating educational outcomes can help improve their effectiveness. It is
      unknown how specific educational outcomes associate with each other among
      learners using online curricula. We set out to study how two educational
      outcomes, learner satisfaction and knowledge, and the learner's year of training
      and training hospital, were associated with one another among learners accessing
      a widely used online curriculum. METHODS: Using data from the 2006-2007 academic
      year, learner satisfaction was compared with pretest knowledge, posttest
      knowledge, changes in knowledge, module topic, year of training, and training
      hospital among 3229 residents at 73 internal medicine residency training
      programs. A multivariable model was used to calculate the odds ratio of learner
      satisfaction relative to changes in knowledge. RESULTS: Module topic, year of
      training, and hospital type were associated with learner satisfaction. Second
      year residents were more satisfied with training modules (mean rating 4.01) than
      first- and third-year residents (mean ratings 3.97 and 3.95, respectively; P <
      0.05). Learner satisfaction was greater among community hospital residents than
      university hospital residents (mean rating 4.0 vs 3.92; P < 0.05). Learner
      satisfaction was greater in residents with high pretest and high posttest
      knowledge (P < 0.05). In multivariate analyses, greater gains in knowledge were
      associated with greater learner satisfaction (P < 0.05). CONCLUSIONS: Greater
      learner satisfaction is associated with greater baseline knowledge, greater
      knowledge after completing a curriculum, and greater improvement in knowledge
      while enrolled in a curriculum.

PMID- 22864093
TI  - Commentary on "Factors affecting learner satisfaction with an internet-based
      curriculum".

PMID- 22864094
TI  - Nasogastric tube feedings and gastric residual volume:  a regional survey.
AB  - OBJECTIVES: To maintain adequate nutrition for patients who are in need, enteral
      feeding via nasogastric tube (NGT) is necessary. Although the literature suggests
      the safety of continued NGT feeding at a gastric residual volume of <400 mL,
      inconsistencies in withholding tube feeding based on residual volume have been
      observed in clinical practice. We performed a regional survey to determine the
      range of current practice among nursing staff regarding the decision to withhold
      NGT feeding based on residual volume and the factors that influence the decision
      making process. METHODS: A questionnaire was designed to evaluate nursing
      practice patterns regarding the decision of withholding NGT feeding based on a
      certain residual volume, which was distributed to the nursing staff at all major
      hospitals in the Oklahoma City metropolitan area. Statistical analysis was done
      with the Fisher exact test. All of the statistical tests were carried out at
      alpha = 0.05. RESULTS: A total of 582 nurses completed the survey. Residual
      volumes (milliliters) resulting in the termination of NGT feeding occurred in 89%
      of nurses at volumes <300 mL and only 3% of nurses at volumes >400 mL. Three main
      reasons for nurses to withhold NGT feeding were risk of aspiration (90%),
      potential feeding intolerance (81%), and risk of regurgitation (67%). Other less
      common concerns were abdominal distension and abdominal discomfort. CONCLUSIONS:
      The decision of withholding NGT feeding varied among the nursing staff that were
      surveyed. A consensus is necessary for the standardization of withholding NGT
      feeding in clinical practice among nursing staff.

PMID- 22864095
TI  - Respiratory syncytial virus morbidity and outpatient palivizumab dosing in South
      Carolina, 2004-2009.
AB  - OBJECTIVE: Respiratory syncytial virus (RSV) has been identified as an important
      cause of lower respiratory tract disease in infants. In patients at high risk,
      prevention is attempted through immunoprophylaxis with palivizumab. In 2008, as a
      result of revisions to the American Academy of Pediatrics' guidelines, South
      Carolina Medicaid reduced the number of approved palivizumab doses from six to
      five. This study attempted to determine whether the reduction of approved doses
      would affect hospitalization and emergency department visits and to characterize
      dose administration. METHODS: We obtained data for all South Carolina Medicaid
      reimbursed births from November 2004 through March 2009. For each RSV season,
      infants who should have received palivizumab were identified. Rates of outpatient
      palivizumab dosing and hospitalizations and emergency department visits because
      of RSV also were identified. RESULTS: In the seasons sampled, 1956 infants met
      eligibility criteria for our study. Infants younger than 29 weeks' gestation
      received 34% to 48% of their total eligible palivizumab doses, whereas infants 29
      to 31 weeks' gestation received 36% to 46% of their doses. The rate of emergency
      department visits and inpatient admissions because of RSV did not differ
      significantly across years. DISCUSSION: In evaluating our primary outcome, there
      was no increase in hospitalizations or emergency department visits. Overall, we
      did note a poor dosing rate in all of the groups. A statistically significant
      decline in dosing per eligible month was noted following the dose reductions.
      Despite solid evidence of the benefits of palivizumab in high-risk groups, we are
      doing an inadequate job of dosing these patients. CONCLUSIONS: We believe
      adherence to current recommendations for palivizumab dosing is suboptimal in
      preterm infants insured by the South Carolina Medicaid program. Healthcare
      professionals must work harder to identify and follow-up with patients who
      qualify for palivizumab dosing, including infants who meet criteria for a second
      season.

PMID- 22864096
TI  - Fatal falls in an ethnically diverse urban community: the link between
      demographic factors and the circumstances surrounding fatal falls.
AB  - OBJECTIVES: Fatal falls cause more than 15,000 deaths per year in the United
      States. Despite this, the circumstances surrounding fatal falls in elderly adults
      are poorly understood. It is unknown whether these circumstances differ across
      ethnicities, although Hispanic American individuals are at reduced risk for fatal
      falls. This study sought to describe fatal falls in an urban, predominantly
      Hispanic, and white non-Hispanic community and to determine the association of
      demographics with the circumstances surrounding these falls (proximate factors).
      METHODS: The death certificates and medical examiners' reports for all 328
      elderly individuals experiencing a fatal fall in Miami-Dade County, FL, from 2005
      to 2007 were reviewed for demographic and proximate factors such as the preceding
      activity and fall location. RESULTS: Fatal falls in elderly adults were
      experienced mostly by individuals living in the community (80%) and affected all
      demographic subgroups, although 80% occurred in individuals older than 74 years.
      Most fatal falls occurred at home (74%), indoors (75%), and during nonvigorous
      activities such as walking (58%) and these tended to affect the oldest elderly.
      In addition, a significant number of fatal falls occurred in public locations,
      outdoors, and during vigorous activity, with these falls tending to affect
      younger individuals living without family. Hispanic ethnicity was not associated
      with proximate factors. CONCLUSIONS: Fatal fall prevention is needed for elderly
      individuals living in the community and should target the oldest elderly adults
      living at home while helping to ensure that individuals who are living without
      family have the appropriate support. These data suggest that Hispanic individuals
      may benefit from prevention strategies developed in other populations.

PMID- 22864097
TI  - Reporting potential conflicts of interest among authors of professional medical
      societies' guidelines.
AB  - BACKGROUND: Limited attention is directed to the potential conflicts of interest
      (COI) of the authors of practice guidelines writing groups of professional
      medical societies (PMS) and industry. The objective of this study was to report
      the proportion of authors with potential COI among guidelines writing groups of
      PMS. METHODS: A systematic search in PubMed to identify practice guidelines of a
      convenience sample of 12 publicly known PMS for a period of 3 years. The authors'
      disclosures of COI were reviewed for the identified guidelines. RESULTS: We
      identified 126 guidelines, of which 107 (85%) reported authors' disclosures of
      COI and 19 (15%) did not. With the exception of the US Preventive Services Task
      Force, all of the reviewed guidelines writing groups of PMS had potential COI to
      some extent. The maximum percentage of authors with potential COI varied among
      PMS from 25% to 100%. CONCLUSIONS: A substantial variation of percentage of
      authors with potential COI exists among guidelines writing groups of different
      PMS. Several practice guidelines of PMS fail to include the disclosures of
      potential COI in their published guidelines. We made several suggestions to
      promote the transparency of potential COI in clinical practice guidelines.

PMID- 22864098
TI  - Commentary on "Reporting potential conflicts of interest among authors of
      professional medical societies' guidelines".

PMID- 22864099
TI  - Small cell lung cancer:  time to diagnosis and treatment.
AB  - OBJECTIVES: Small cell lung cancer (SCLC) is the most rapidly progressive form of
      lung cancer, and delays in treatment may increase the tumor burden. We determined
      the time from abnormal radiograph to diagnosis and treatment for patients with
      SCLC and investigated the effect of emergent presentation, stage, radiographic
      findings, and race on these measures and survival. METHODS: Retrospective
      analysis of clinical data for 45 consecutive evaluable patients at a single
      institution diagnosed as having SCLC. RESULTS: Median time from first abnormal
      radiograph to tissue diagnosis was 10 days and time from first abnormal
      radiograph to initiation of treatment was 35 days. Emergency department
      presentation led to earlier diagnosis compared with the clinic (3 vs 21 days),
      with a trend toward earlier treatment (15 vs 39 days; P = 0.057). No significant
      effect of radiographic findings, disease stage, or race was observed from time to
      diagnosis or treatment. Forty-three patients (96%) died, with a median survival
      time from initial abnormal radiograph to death of 375 days. Survival was longer
      for patients with limited stage disease (619 vs 230 days), but it was not
      significantly affected by emergent presentation, radiographic findings, or race.
      Consistent with the aggressive behavior of SCLC, 10 patients (22%) had a normal
      radiograph within 6 months prediagnosis, and 7 of these had extensive disease.
      CONCLUSIONS: The median time from abnormal radiograph to initiation of treatment
      for SCLC in our single-center study overlapped with the expected doubling time
      for this malignancy and likely allowed a preventable increase in tumor burden.

PMID- 22864100
TI  - Commentary on "Small cell lung cancer: time to diagnosis and treatment".

PMID- 22864101
TI  - Prognostic value of cardiac-specific troponins in intracranial hemorrhage.
AB  - BACKGROUND: Cardiac-specific troponin (Tn) serum concentrations have proved to be
      important diagnostic and prognostic markers for acute myocardial infarction.
      Elevated levels in the setting of noncardiac diseases such as intracerebral
      hemorrhage also may provide useful prognostic information regarding outcome.
      METHODS: A systematic review of the English-language medical literature was
      performed using PubMed. Articles reporting original data were included. RESULTS:
      Ten reports qualified for review. A spectrum of cardiac abnormalities was
      observed in studied patients, sometimes more frequently in those with Tn
      elevations, whereas some had no such abnormalities, even if Tn was detected.
      Although some studies suggested a worse outcome in patients with elevated Tn
      levels, the findings were inconsistent. CONCLUSIONS: At this time, although the
      literature suggests an association between cardiac-specific Tn elevations and
      clinical events in patients with intracranial hemorrhage, data are insufficient
      to conclude that there is a consistent predictive value or to recommend routine
      Tn monitoring for prognosis.

PMID- 22864102
TI  - Telaprevir and boceprevir in African Americans with genotype 1 chronic hepatitis
      C: implications for patients and providers.
AB  - Telaprevir and boceprevir have received US Food and Drug Administration approval
      for use as triple therapy with pegylated interferon and ribavirin in genotype 1
      chronic hepatitis C virus (HCV) infection. Clinical trials of these agents
      included few African Americans, despite the overwhelming need for improved
      therapies in this racial group. Although African Americans are predicted to have
      improved response rates with this new treatment paradigm, clinical trials
      illustrate lower rates of sustained virologic response for this racial group
      versus whites. African Americans with genotype 1 HCV infection appear to require
      longer durations of therapy than do whites to achieve a sustained virologic
      response. Further investigation is required to adequately counsel African
      Americans with genotype 1 chronic HCV infection on the efficacy of telaprevir and
      boceprevir in their racial group. Increased participation of this racial group in
      HCV clinical trials is needed to improve therapies in this difficult-to-treat
      population.

PMID- 22864103
TI  - Pharmacotherapy considerations in elderly adults.
AB  - Life expectancy for Americans has increased dramatically since 1900, as have the
      available pharmacotherapeutic options. Unfortunately, pharmacotherapy mishaps
      occur commonly in the older adult population. This problem greatly affects the
      morbidity and mortality of elderly patients and greatly increases healthcare
      costs. To improve patient care among elderly adults, healthcare practitioners
      must consider several issues when developing a pharmacotherapy plan. A thorough
      understanding of pharmacokinetics, pharmacodynamics, adverse drug reactions, drug
      interactions, and several other factors is necessary for practitioners to develop
      a safe and effective drug therapy plan for older adults. This review provides a
      general but comprehensive review of the issues pertaining to pharmacotherapy in
      elderly people and offers several suggestions for improving their pharmaceutical
      care.

PMID- 22864104
TI  - Purple urine bag syndrome: it is the urine bag and not the urine that is
      discolored purple.

PMID- 22864106
TI  - Patients' perceived support from physicians and the role of hospital
      characteristics.
AB  - OBJECTIVE: Through patient-physician communication, physicians can support breast
      cancer patients in coping with the diagnosis and treatment of their cancer.
      Research on the influence of hospital characteristics on patient-reported
      outcomes suggests that patient-physician communication may be shaped by the
      hospital environment. The aim of this study is to investigate the relationship
      between hospital characteristics and breast cancer patients' perceptions of the
      support provided by physicians. DESIGN: Data from two cross-sectional surveys
      conducted in 2007 were combined and hierarchical logistic regression models were
      calculated. SETTING: Newly diagnosed breast cancer patients treated in breast
      center hospitals in North Rhine-Westphalia and at least one key person from these
      hospitals were surveyed. PARTICIPANTS: Data from 3285 newly diagnosed breast
      cancer patients and 172 key persons from 87 breast center hospitals were used.
      MAIN OUTCOME MEASURE: The patients' perceptions of support from physicians were
      measured with three items from the Cologne Patient Questionnaire. Physician
      support was studied in relation to patient characteristics as well as hospital
      structure and processes. RESULTS: The multilevel model showed that breast cancer
      patients perceived themselves as receiving less support from the physician when
      there were problems within the hospitals' organization of care, independent of
      patient characteristics. CONCLUSION: This study provides preliminary evidence
      that the quality of patient-physician communication depends not only on the
      patient or physician but also on hospital organization. Further studies should be
      conducted to determine the extent to which interventions for improving quality at
      the hospital level can modify physician communication performance.

PMID- 22864107
TI  - Types and patterns of safety concerns in home care: staff perspectives.
AB  - BACKGROUND: Quality health care in the home is dependent on having a safe
      environment to provide care. This analysis is based on the data from a larger
      study aimed at understanding key issues in the delivery and receipt of home
      support services from the perspectives of home support workers (HSWs), older
      adult clients and family members. This analysis focuses on HSWs perspectives of
      safety. OBJECTIVE: To explore the types and patterns of safety concerns staff
      encountered in home care settings. DESIGN: In-depth, semi-structured interviews
      were conducted with HSWs. The analysis included topic and analytical coding of
      workers' verbatim accounts. SETTING: Interviews were completed in British
      Columbia, Canada. PARTICIPANTS: A total of 115 HSWs participated. The average age
      was 50 years, and the average tenure in this sector was 11.5 years. Fully, 71% of
      workers had completed at least some college-level education, and 69% of workers
      were born outside of Canada. RESULTS: Workers identified four types of safety
      concerns: physical, spatial, interpersonal and temporal. We developed a
      conceptual model of HSW safety that demonstrates the: types of safety concerns;
      the multi-dimensional and intersectional nature of safety concerns and the
      factors that intensify or mitigate safety concerns. CONCLUSIONS: Our study
      identifies numerous HSW safety concerns, each requiring tailored interventions
      and strategies. Where multiple concerns intersect, the complexity and precarious
      nature of the home care workspace is revealed. The identification of mitigating
      and intensifying factors points to future interventions.

PMID- 22864108
TI  - Comment: clinical experience with complications of hand rejuvenation.

PMID- 22864109
TI  - The in vitro effect of probiotic Vagococcus fluvialis on the innate immune
      parameters of Sparus aurata and Dicentrarchus labrax.
AB  - In this study we evaluated the effect of the probiotic Vagococcus fluvialis on
      the cellular immune unspecific system of two different fish species of great
      interest in aquaculture such as gilthead sea bream (Sparus aurata) and European
      sea bass (Dicentrarchus labrax). Leucocytes from head kidney of the two fish
      species were extracted and concentration adjusted to 10(7) cells ml(-1).
      Phagocytic and respiratory burst activity and the peroxidase content of
      leucocytes were observed 30 min after incubation with the probiotic Vagococcus
      fluvialis alive or inactivated with heat shock or UV-light at different
      concentrations of 10(7), 10(8), 10(9) cfu ml(-1) (final concentration 10(6),
      10(7), 10(8) cfu ml(-1)). V. fluvialis produced dose-dependent increments in
      respiratory burst in sea bream leucocytes. The respiratory burst activity of sea
      bream head kidney leucocytes incubated with 10(6) cfu ml(-1) of live and
      inactivated bacteria was not stimulated. The highest values of peroxidase content
      were observed in sea bass cells with stimulation indexes higher than 1 in HK
      leucocytes incubated with 10(8) cfu ml(-1) of live and inactivated bacteria.
      Statistical analysis revealed that differences being only significant in sea bass
      leucocytes where 10(8) cfu ml(-1) bacteria denote statistically significant
      differences (P < 0.05) respect to other concentrations. Highest values of
      phagocytic activity were obtained in sea bass macrophages incubated with UV-light
      inactivated bacteria (27.33% +/- 1.45), where significantly differences with sea
      bass HK leucocytes were detected. Our results suggest that the in vitro assays
      are a useful tool to optimize the effective dose of probiotic bacteria. Although
      in vivo studies are necessary to confirm the immunomodulatory effect of this
      strain.

PMID- 22864111
TI  - Metformin targets ovarian cancer stem cells in vitro and in vivo.
AB  - PURPOSE: Studies in non-gynecologic tumors indicate that metformin inhibits
      growth of cancer stem cells (CSC). Diabetic patients with ovarian cancer who are
      taking metformin have better outcomes than those not taking metformin. The
      purpose of this study was to directly address the impact of metformin on ovarian
      CSC. METHODS: The impact of metformin on ovarian cancer cell line growth and
      viability was assessed with trypan blue staining. Aldehyde dehydrogenase (ALDH)
      expressing CSC were quantified using FACS(r). Tumor sphere assays were performed
      to determine the impact of metformin on cell line and primary human ovarian tumor
      CSC growth in vitro. In vivo therapeutic efficacy and the anti-CSC effects of
      metformin were confirmed using both tumor cell lines and ALDH(+) CSC tumor
      xenografts. RESULTS: Metformin significantly restricted the growth of ovarian
      cancer cell lines in vitro. This effect was additive with cisplatin. FACS
      analysis confirmed that metformin reduced ALDH(+) ovarian CSC. Consistent with
      this, metformin also inhibited the formation of CSC tumor spheres from both cell
      lines and patient tumors. In vivo, metformin significantly increased the ability
      of cisplatin to restrict whole tumor cell line xenografts. In addition, metformin
      significantly restricted the growth of ALDH(+) CSC xenografts. This was
      associated with a decrease in ALDH(+) CSC, cellular proliferation, and
      angiogenesis. CONCLUSIONS: Metformin can restrict the growth and proliferation of
      ovarian cancer stem cells in vitro and in vivo. This was true in cell lines and
      in primary human CSC isolates. These results provide a rationale for using
      metformin to treat ovarian cancer patients.

PMID- 22864112
TI  - (Laterally) extended endopelvic resection: surgical treatment of locally advanced
      and recurrent cancer of the uterine cervix and vagina based on ontogenetic
      anatomy.
AB  - OBJECTIVE: Pelvic exenteration is mainly applied as a salvage operation for a
      subset of patients with persistent and recurrent cervicovaginal cancer. The
      procedure can also cure locally advanced primary disease not suitable for
      radiotherapy. However, high operative abortion and intralesional tumor resection
      rates significantly limit its clinical benefit. To improve locoregional tumor
      control we have proposed to establish cancer surgery on ontogenetic anatomy and,
      consequently, we have developed the (Laterally) Extended Endopelvic Resection
      ((L)EER). METHODS: (L)EER is clinically and histopathologically evaluated with a
      monocentric prospective observational study. Patients with advanced and recurrent
      cervicovaginal cancer are treatment candidates if distant metastases and tumor
      fixation at the region of the sciatic foramen can be excluded. RESULTS: 91
      patients with locally advanced primary (n=30) and recurrent or persistent (n=61)
      carcinoma of the cervix and vagina were treated with (L)EER. 74% of the tumors
      were fixed to the pelvic wall. No (L)EER treatment was aborted, R0 resection was
      histopathologically confirmed in all cases. (L)EER definitively controlled the
      locoregional cancer in 92% (95% CI: 85-99) of the patients. Five year overall
      survival probability was 61% (95% CI: 49-72). CONCLUSIONS: The results of (L)EER
      treatment confirm the concept of cancer surgery based on ontogenetic anatomy. In
      patients with locally advanced and recurrent cervicovaginal cancer (L)EER
      achieves locoregional tumor control both with central disease and with tumors
      fixed to the pelvic side wall except at the region of the sciatic foramen.

PMID- 22864113
TI  - Noncanonical mismatch repair as a source of genomic instability in human cells.
AB  - Mismatch repair (MMR) is a key antimutagenic process that increases the fidelity
      of DNA replication and recombination. Yet genetic experiments showed that MMR is
      required for antibody maturation, a process during which the immunoglobulin loci
      of antigen-stimulated B cells undergo extensive mutagenesis and rearrangements.
      In an attempt to elucidate the mechanism underlying the latter events, we set out
      to search for conditions that compromise MMR fidelity. Here, we describe
      noncanonical MMR (ncMMR), a process in which the MMR pathway is activated by
      various DNA lesions rather than by mispairs. ncMMR is largely independent of DNA
      replication, lacks strand directionality, triggers PCNA monoubiquitylation, and
      promotes recruitment of the error-prone polymerase-eta to chromatin. Importantly,
      ncMMR is not limited to B cells but occurs also in other cell types. Moreover, it
      contributes to mutagenesis induced by alkylating agents. Activation of ncMMR may
      therefore play a role in genomic instability and cancer.

PMID- 22864114
TI  - Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.
AB  - During prometaphase, dense microtubule nucleation sites at centrosomes form
      robust spindles that align chromosomes promptly. Failure of centrosome maturation
      leaves chromosomes scattered, as seen routinely in cancer cells, including
      myelodysplastic syndrome (MDS). We previously reported that the Miki (LOC253012)
      gene is frequently deleted in MDS patients, and that low levels of Miki are
      associated with abnormal mitosis. Here we demonstrate that Miki localizes to the
      Golgi apparatus and is poly(ADP-ribosyl)ated by tankyrase-1 during late G2 and
      prophase. PARsylated Miki then translocates to mitotic centrosomes and anchors CG
      NAP, a large scaffold protein of the gamma-tubulin ring complex. Due to
      impairment of microtubule aster formation, cells in which tankyrase-1, Miki, or
      CG-NAP expression is downregulated all show prometaphase disturbances, including
      scattered and lagging chromosomes. Our data suggest that PARsylation of Miki by
      tankyrase-1 is a key initial event promoting prometaphase.

PMID- 22864115
TI  - Close proximity to Igh is a contributing factor to AID-mediated translocations.
AB  - Class switch recombination (CSR) has the potential to generate genomic
      instability in B cells as activation-induced cytidine deaminase (AID), which
      mediates this process, is known to target many sites outside Igh. Nonetheless we
      do not fully understand what factors influence AID targeting genome-wide. Given
      that errors in CSR can lead to dangerous, oncogenic chromosomal translocations it
      is important to identify the elements that determine which genes are at risk of
      being "hit" and could be involved in aberrant rearrangements. Here we have
      investigated the influence of nuclear organization in determining "off-target"
      activity and the choice of fusion partners. Our studies indicate that the vast
      majority of known AID-mediated Igh translocation partners are found in
      chromosomal domains that contact this locus during class switching. Further,
      these interaction domains can be used to identify other genes that are hit by
      AID.

PMID- 22864117
TI  - Multisite ribosomal stalling: a unique mode of regulatory nascent chain action
      revealed for MifM.
AB  - Bacillus subtilis MifM uses polypeptide-instructed ribosomal stalling to control
      translation of YidC2, a membrane protein biogenesis factor. In contrast to other
      stalling systems involving a single arrest point, our in vitro
      translation/toeprint experiments show that the B. subtilis ribosome stalls
      consecutively at multiple codons of MifM. This mode of elongation arrest depends
      on nascent chain residues at the middle of the ribosomal exit tunnel and a few
      (four for the maximum functionality) negative charges residing proximally to the
      arrest points. The latter element does not require exact amino acid sequence, and
      this feature may underlie the multisite stalling. The arrested nascent chains
      were not efficiently transferred to puromycin, suggesting that growing MifM
      nascent chains inhibit peptidyl transferase center after acquiring an acidic
      residue(s). Multisite stalling seems to provide a unique means for MifM to
      achieve a sufficient duration of ribosomal stalling required for the regulatory
      function.

PMID- 22864116
TI  - RNase H2-initiated ribonucleotide excision repair.
AB  - Ribonucleotides are incorporated into DNA by the replicative DNA polymerases at
      frequencies of about 2 per kb, which makes them by far the most abundant form of
      potential DNA damage in the cell. Their removal is essential for restoring a
      stable intact chromosome. Here, we present a complete biochemical reconstitution
      of the ribonucleotide excision repair (RER) pathway with enzymes purified from
      Saccharomyces cerevisiae. RER is most efficient when the ribonucleotide is
      incised by RNase H2, and further excised by the flap endonuclease FEN1 with
      strand displacement synthesis carried out by DNA polymerase delta, the PCNA
      clamp, its loader RFC, and completed by DNA ligase I. We observed partial
      redundancy for several of the enzymes in this pathway. Exo1 substitutes for FEN1
      and Pol epsilon for Pol delta with reasonable efficiency. However, RNase H1 fails
      to substitute for RNase H2 in the incision step of RER.

PMID- 22864118
TI  - Combining chemoenzymatic monomer transformation with ATRP: a facile "one-pot"
      approach to functional polymers.
AB  - A facile "one-pot" chemoenzymatic-ATRP has been successfully developed through
      the combination of copper-catalytic ATRP and enzyme-catalytic monomer
      transformation reactions.

PMID- 22864119
TI  - Myocardial infarction and normal coronary arteries: the experience of the
      cardiology department of Sfax, Tunisia.
AB  - OBJECTIVE: The purpose of the present study is to describe our experience with
      patients who have a transmural myocardial infarction (MI) in the presence of a
      normal coronary artery. The clinical profile, demographic characteristics and
      outcomes of these patients are discussed. METHODS: Between January 2006 and
      August 2011, 21 patients who presented with a Q-wave myocardial infarction were
      found to have normal coronary arteries. The prevalence rate of this entity was
      1.5% (21 out of 1,400 Q wave MI patients). These patients were characterized by
      their young age (the mean age=44.95+/-14.86), male dominance (90.47%), and a high
      prevalence of smoking (85.71%). In this study, 4 patients have an evident
      spontaneous spasm shown on coronary angiography which disappeared after
      intracoronary injection of nitrates. Coagulation Disorders, such as activated
      protein C resistance (APC) resistance, protein C deficiency and antiphospholipid
      antibody syndrome were found in 4 of 12 patients who underwent systematic
      examination. One patient had a history of lung cancer which may be associated
      with a hypercoagulable state and may explain the occurrence of myocardial
      infarction with a normal coronary artery. The mean left ventricle ejection was
      56. 5+/-12. The mean follow-up was 24+/-10 months. Six patients developed
      residual chest pain which was generally easily controlled by anti-spastic therapy
      and no patient had a major cardiovascular event. CONCLUSION: Patients with Q-wave
      MI and with normal coronary arteries seem to have a good short and long-term
      prognosis especially when they are treated with an exclusive medical strategy.

PMID- 22864120
TI  - Clinical outcomes of Japanese MPO-ANCA-related nephritis: significance of initial
      renal death for survival.
AB  - OBJECTIVE: Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-
      related nephritis constitutes 60% of rapidly progressive glomerulonephritis
      (RPGN) in Japan. The reported 1-year survival rate is over 80%, however, the long
      term prognosis remains unknown. We therefore investigated the prognosis and
      factors affecting the clinical course of patients. METHODS: We retrospectively
      investigated 74 patients (female, n=42; median age, 73.0 years) with MPO-ANCA
      related nephritis. The patients were admitted to Fukushima Medical University and
      two affiliated hospitals between 2000 and 2010. RESULTS: Median estimated GFR
      (eGFR) was 12.1 mL/min/1.73 m2 at admission. The Birmingham Vasculitis Activity
      Score (BVAS version 3: max 63 points) at diagnosis and at 4 weeks after start of
      treatment were 15.0 and 5.0, respectively. Twenty-three patients (31%) died
      during a median observation period of 30.5 months. Sixteen patients (22%)
      presented with end-stage renal disease (ESRD) at the initial phase, and needed
      regular dialysis therapy. Multivariate Cox proportional hazards model analysis
      revealed that renal death at the initial phase was a significant risk factor for
      all-cause death (Hazard ratio, 5.72; 95% confidence interval, 2.49-13.09;
      p<0.001). Furthermore, BVAS>6, evaluated 4 weeks after start of treatment, is an
      independent risk factor for ESRD and patient survival. CONCLUSION: This is the
      first investigation to demonstrate clinical features focusing on MPO-ANCA-related
      nephritis. Renal death at the initial phase of treatment is a powerful risk
      factor for all-cause death in patients with MPO-ANCA-related nephritis. Patients
      at high risk of death and ESRD could be stratified according to BVAS.

PMID- 22864121
TI  - Diagnostic problems among chronic lymphocytic leukemia and other indolent B-cell
      leukemias in a Japanese population.
AB  - OBJECTIVE: Japanese chronic lymphocytic leukemia (CLL) provides a diagnostic
      dilemma due to the low incidence and the heterogeneity shown in its morphology
      and immunophenotype. We clarified the diagnostic problems in Japanese CLL through
      our retrospective observation. METHODS: Between 2006 and 2011, we found a total
      of 48 cases with CLL and other indolent B-cell leukemias. We made a diagnosis of
      true CLL based on clinical, laboratory, immunophenotypic and cytogenetic data.
      RESULTS: Among the 48 cases, only 28 cases (58.3%) were diagnosed with true CLL.
      Morphologic evaluation using a forced-air dried preparation alone is not helpful
      to distinguish CLL from other indolent B-cell leukemias, including hairy cell
      leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and splenic marginal
      zone lymphoma. CLL immunophenotypic score should be more strictly applied in
      Japan than in Western countries. CONCLUSION: Fluorescence in situ hybridization
      for CCND1/IGH, the presence of leukocytosis and lymphadenopathy at diagnosis, and
      the morphological evaluation using naturally air dried preparations are important
      clues to make a correct diagnosis of Japanese CLL.

PMID- 22864122
TI  - Images in cardiovascular medicine: tuberculous aortitis.
AB  - Tuberculous aortitis is a rare disease entity indicative of disseminated
      tuberculosis. We report a case who presented with newly diagnosed hypertension
      one year after her last admission for pulmonary and pericardial tuberculosis.
      Chest CT and MRA, performed due to marked differences in pulse amplitude between
      upper and lower limbs, demonstrated long and severe segmental stenosis of the
      thoracic aorta. After the operation of bypass graft for the thoracic aorta, the
      patient recovered uneventfully. Tuberculous aortitis should be included in the
      list of differential diagnosis for secondary hypertension, especially if the
      patient has a recent disease history of pulmonary tuberculosis.

PMID- 22864123
TI  - Agranulocytosis immediately after oral administration of cibenzoline and
      dabigatran in a patient with paroxysmal atrial fibrillation.
AB  - This case report describes agranulocytosis immediately after oral administration
      of cibenzoline and dabigatran in a 70-year-old woman with paroxysmal atrial
      fibrillation (AF). No blasts were found in peripheral blood and bone marrow, and
      the white blood cell count increased abruptly by intravenous administration of
      granulocyte colony-stimulation factor, suggesting an allergic response caused by
      cibenzoline or dabigatran, or both. Though antiarrhythmic drugs with
      anticoagulation therapy are commonly used to treat paroxysmal AF, caution has to
      be paid to drug-induced agranulocytosis.

PMID- 22864124
TI  - A case of chronic hepatitis C with nephrotic diabetic nephropathy who achieved
      sustained viral remission by double-filtration plasmapheresis and interferon
      combination therapy.
AB  - We report a 66-year-old man with chronic hepatitis caused by hepatitis type C
      virus of genotype-1b and high-viral-load combined with cryoglobulinemia and
      advanced diabetic nephropathy in whom we successfully achieved viral removal and
      eradication by DFPP (VRAD). The dose of PEG-interferon was reduced to 70 mg/week
      due to thrombocytopenia. Rivavirin was discontinued at day 21 due to anemia. Even
      with treatment of PEG-interferon alone, the condition was judged to be sustained
      viral remission at the end of the observation. This is a successful report of
      VRAD in a combined case of diabetic and HCV-related cryoglobulin-nephropathy with
      nephrotic syndrome. The therapeutic effect of IFN seemed to be efficiently
      enhanced by concomitant DFPP (VRAD therapy).

PMID- 22864126
TI  - Streptococcus pneumoniae-associated hemolytic uremic syndrome in a splenectomized
      adult patient.
AB  - A 62-year-old splenectomized woman was admitted because of upper respiratory
      tract symptoms, general fatigue, and purpura. Laboratory data demonstrated
      microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and a
      positive Streptococcus pneumoniae (SP) urinary antigen test. A renal biopsy
      showed thrombotic microangiopathic changes. She was diagnosed with hemolytic
      uremic syndrome (HUS) secondary to SP infection. Methylprednisolone pulse therapy
      in addition to antibiotic therapy led to prompt improvement of her symptoms and
      laboratory abnormalities. This is the first adult case of SP-associated HUS
      successfully treated without hemodialysis. SP infection should be considered as a
      causative etiology in all splenectomized patients with HUS.

PMID- 22864125
TI  - Culture-negative peritonitis caused by splenic infarction in a continuous
      ambulatory peritoneal dialysis patient.
AB  - A 43-year-old diabetic woman on peritoneal dialysis, developed left upper
      abdominal pain and culture-negative cloudy peritoneal dialysate. The dialysate
      had WBC counts of 1,532/uL with 90% polymorphonuclear cells. The patient did not
      respond well to anti-bacterial therapy. Abdominal CT scan revealed diffuse
      atherosclerosis in the abdominal vessels and wedge-shaped splenic infarction.
      Anticoagulation therapy was initiated and an improvement in peritonitis was
      observed without peritoneal catheter removal. Thus, in peritoneal dialysis
      patients with diffuse atherosclerosis or the risk of systemic embolization,
      symptoms of unexplained left upper quadrant pain and culture-negative peritonitis
      should be evaluated to rule out splenic infarction.

PMID- 22864127
TI  - Pneumomediastinum and striking family history: uncommon case of Birt-Hogg-Dube
      syndrome.
AB  - Birt-Hogg-Dube syndrome is a rare autosomal dominant condition caused by a
      germline mutation in the folliculin gene, which is characterized by skin
      fibrofolliculomas, multiple lung cysts and renal cancer. The clinical expression
      of the syndrome is highly variable, with recurrent pneumothoraces due to ruptured
      lung cysts in many cases. We report a patient with pneumomediastinum and cervico
      facial emphysema after severe coughing without pneumothorax, skin lesions or
      renal tumour, but a striking family history of lung abnormalities.

PMID- 22864128
TI  - Successful treatment by fibrin glue sealant for pneumothorax with chronic GVHD
      resistant to autologous blood patch pleurodesis.
AB  - Pneumothorax associated with chronic graft-versus-host disease (cGVHD) after stem
      cell transplantation is a rare complication. Autologous blood has been used
      successfully for pleurodesis, which was less toxic than chemical agents. However,
      when pneumothorax is resistant to pleurodesis, no other procedure is more
      effective and conservative. Here, we describe a case of myelodysplastic syndromes
      complicated with cGVHD-related pneumothorax. His pneumothorax has been resistant
      to pleurodesis using autologous blood and was treated successfully with fibrin
      glue sealant. In our limited experience, we believe the best success could be
      achieved when this method is used to treat persistent pneumothorax with cGVHD.

PMID- 22864129
TI  - Sub-acute demyelinating polyradiculoneuropathy as an initial symptom of
      peripheral T cell lymphoma, not otherwise specified (PTCL-NOS).
AB  - Here we report the first case of peripheral T-cell lymphoma, not otherwise
      specified (PTCL-NOS), who initially presented with peripheral neuropathy. Nerve
      conduction, cerebral spinal fluid studies and his clinical course were compatible
      with sub-acute demyelinating polyradiculoneuropathy. In addition, left cervical
      lymph node swelling was observed on admission. Diagnosis of PTCL-NOS was made by
      the histological, immunohistochemical, and Southern blot analyses on the biopsy
      specimen from the enlarged lymph node. Combination chemotherapy composed of
      cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) was effective
      for polyneuropathy as well as for lymphoma. Several antibodies relating to
      paraneoplastic syndrome such as Ma1, Ma2, Amphiphysin, CV2, Ri, Yo and Hu were
      all negative. Because sural nerve biopsy performed prior to CHOP therapy revealed
      no infiltration of lymphoma cells, immune dysfunction mediated by some cytokine
      or unidentified autoantibody related to PTCL-NOS was thought to be involved in
      the polyradiculoneuropathy.

PMID- 22864130
TI  - Radicular myoclonus in a patient with Guillain-Barre Syndrome.
AB  - A 53-year-old Japanese woman presented with myoclonus during the course of
      Guillain-Barre syndrome. The myoclonus was characterized by relatively regular
      involuntary movements, starting from proximal muscles of the right lower leg, and
      moving almost simultaneously towards the left lower leg and upper trunk. Surface
      electromyography revealed rhythmic synchronous discharges with 100-200 ms
      duration in the agonist and antagonist muscles at approximately 4 Hz. The jerk
      locked back averaging, long latency reflexes, and somatosensory evoked potentials
      studies were normal. We report myoclonus due to radiculitis in a patient with
      Guillain-Barre syndrome.

PMID- 22864131
TI  - Decreased ratio of downward to horizontal smooth pursuit eye movement velocity in
      a patient with Chiari I malformation: application in early detection of
      vestibulocerebellar malfunction.
AB  - A 72-year-old man presented with dizziness and left hand muscle atrophy. Magnetic
      resonance imaging revealed a spinal cord cavity and descent of the cerebellar
      tonsils. His diagnosis was Chiari I malformation with syringomyelia. No
      cerebellar signs were observed on physical examination. The cause of dizziness
      was investigated using a video-based eye movement tracker, which revealed a
      downward smooth pursuit velocity gain significantly below normal when expressed
      relative to the horizontal pursuit velocity gain. Vestibulocerebellar damage can
      cause mild downward pursuit deficit. The downward to horizontal smooth pursuit
      velocity gain ratio may be a more sensitive means of detecting
      vestibulocerebellar damage early.

PMID- 22864132
TI  - Clinico-anatomical analysis of the fibers to the inferior rectus muscle in the
      oculomotor fascicles.
AB  - We report two cases of isolated unilateral pupil-sparing partial fascicular
      oculomotor paresis. Patient 1 was a 72-year-old man who developed left-sided
      palsy of the inferior rectus muscle (IR), medial rectus muscle (MR), superior
      rectus muscle (SR), inferior oblique muscle (IO), and levator palpebrae
      superioris (LP) due to infarction of the left paramedian thalamic artery. Patient
      2 was a 70-year-old woman who developed right-sided palsy of MR, SR, IO and LP
      due to infarction of the right superior paramedian mesencephalic artery. These
      results suggest that the fibers to IR may be located in the most rostral portion
      of the oculomotor fascicles.

PMID- 22864133
TI  - A case of disseminated sporotrichosis treated with prednisolone,
      immunosuppressants, and tocilizumab under the diagnosis of rheumatoid arthritis.
AB  - We encountered a disseminated sporotrichosis patient with polyarthritis and
      progressive skin ulcers, who had been previously treated with prednisolone,
      tocilizmab, tacrolims, and cyclophosphamide under the diagnosis of rheumatoid
      arthritis in another hospital. Making the diagnosis of leukocytoclasticvasculitis
      based on the clinical observation of skin ulcers, we intensified
      immunosuppressive therapy. Unfortunately, the patient developed septic shock.
      Blood culture revealed that the pathogenic organism was sporothrixschenckii. Any
      case of intractable arthritis or skin ulcers, which does not improve, despite
      adequate immunosuppressive therapy, is likely to be suspicious of sporotrichosis.

PMID- 22864134
TI  - Sitagliptin (DPP-4 inhibitor)-induced rheumatoid arthritis in type 2 diabetes
      mellitus: a case report.
AB  - A dipeptidyl peptidase (DPP)-4 inhibitor, commonly used to treat patients with
      type 2 diabetes, has caused concern because of immune system side effects. We
      report a 48-year-old woman with type 2 diabetes who was diagnosed with rheumatoid
      arthritis (RA) after continued polyarthritis and an increase in rheumatoid factor
      up to 86 IU/mL after three months of treatment with sitagliptin, a DPP-4
      inhibitor. The shared epitope (SE)-containing human leukocyte antigen (HLA)-DRB1
      alleles, which are important predisposing factors for RA, were positive. RA might
      have been triggered by sitagliptin due to a predisposing condition.

PMID- 22864135
TI  - Central nervous system relapse of Whipple's disease.
AB  - A 50-year-old man presented with a 12 kg weight loss in 8 months. Upper
      gastrointestinal endoscopy findings showed strong erosion and diffuse bleeding in
      the duodenum. Histopathological findings showed PAS staining-positive macrophages
      consistent with Whipple's disease. He was treated with trimethoprim
      sulfamethoxazole. His condition initially improved. However, during his 6-year
      course of treatment he developed a central nervous system relapse. Tropheryma
      whipplei DNA was detected by a polymerase chain reaction in his cerebrospinal
      fluid. This relapse was successfully treated with ceftriaxone sodium (CTRX). We
      considered that as initial therapy for Whipple's disease, it would be important
      to administer CTRX for at least a few months, due to its high translatability to
      CSF.

PMID- 22864136
TI  - Osteomalacia due to a bladder reconstruction performed 35 years previously.
AB  - We report a 54-year-old man with osteomalacia due to a bladder reconstruction
      performed 35 years previously. He had had slowly progressive chest and back pain
      for 18 months. Osteomalacia due to metabolic acidosis was suspected based on
      hyperalkalinephosphatasemia and a high serum chloride level, and the diagnosis
      was confirmed by bone scintigraphy. His symptoms and blood electrolyte levels
      were improved by oral medication, including sodium hydrogen carbonate.
      Measurement of the serum chloride level is simple and useful for evaluating
      acidosis, for which a regular blood test is essential in patients who have
      undergone bladder reconstruction.

PMID- 22864137
TI  - Peritoneal loose body.

PMID- 22864138
TI  - Ortner's syndrome in a patient with COPD.

PMID- 22864139
TI  - Cavitary pulmonary opacity in a diabetic patient.

PMID- 22864140
TI  - An unusual orbital mass with dural tail signs.

PMID- 22864141
TI  - Balo's concentric sclerosis in multiple sclerosis.

PMID- 22864142
TI  - Internal carotid artery involvement in herpes zoster ophthalmicus.

PMID- 22864143
TI  - Leonine facies in the cutaneous form of multicentric reticulohistiocytosis.

PMID- 22864144
TI  - Metallosis.

PMID- 22864145
TI  - Radiograph abnormalities caused by the nuclear accident.

PMID- 22864147
TI  - Correction: Development and validation of filters for the retrieval of studies of
      clinical examination from medline.

PMID- 22864146
TI  - Oral vaccination with vaccinia virus expressing the tick antigen subolesin
      inhibits tick feeding and transmission of Borrelia burgdorferi.
AB  - Immunization with the Ixodes scapularis protein, subolesin, has previously been
      shown to protect hosts against tick infestation and to decrease acquisition of
      Anaplsma marginale and Babesia bigemina. Here we report the efficacy of
      subolesin, a conserved tick protein that can act as a regulator of gene
      expression, expressed from vaccinia virus for use as an orally delivered
      reservoir - targeted vaccine for prevention of tick infestation and
      acquisition/transmission of Borrelia burgdorferi to its tick and mouse hosts. We
      cloned subolesin into vaccinia virus and showed that it is expressed from
      mammalian cells infected with the recombinant virus in vitro. We then vaccinated
      mice by oral gavage. A single dose of the vaccine was sufficient for mice to
      generate antibody response to subolesin. Vaccination with the subolesin
      expressing vaccinia virus inhibited tick infestation by 52% compared to control
      vaccination with vaccinia virus and reduced uptake of B. burgdorferi among the
      surviving ticks that fed to repletion by 34%. There was a reduction in
      transmission of B. burgdorferi to uninfected vaccinated mice of 40% compared to
      controls. These results suggest that subolesin has potential as a component of a
      reservoir targeted vaccine to decrease B. burgdorferi, Babesia and Anaplasma
      species infections in their natural hosts.

PMID- 22864148
TI  - Dynamic muscle loading and mechanotransduction.

PMID- 22864149
TI  - Incontinentia pigmenti:  presenting with neonatal seizures and diffuse MRI brain
      changes.

PMID- 22864150
TI  - Debates on euthanasia.

PMID- 22864151
TI  - PHARMAC's updated guidelines for cost-utility analyses, with new QALYs per $1M
      metric.

PMID- 22864152
TI  - "I wouldn't want to become a nuisance under any circumstances"--a qualitative
      study of the reasons some healthy older individuals support medical practices
      that hasten death.
AB  - AIM: To explore the reasons some healthy older New Zealanders support medical
      practices that hasten death. METHODS: Recruitment was from the Voluntary
      Euthanasia Society of New Zealand (VESNZ), an organisation that supports legal
      medical assistance in dying. All participants were members of VESNZ. 106
      individuals returned signed consent forms. All interviews took place in the
      participant's home. After 11 interviews, saturation of information was reached
      and interviewing was stopped. RESULTS: An important finding of this study
      indicates that healthy, older individuals who support medical practices that
      hasten death have serious concerns about their (perceived) future incapacities
      and dependency on others, as well as their fears around becoming a burden. The
      study also found that fear of future pain was not a dominant reason to support
      medical assistance to die. CONCLUSION: Our study provides confirmation that the
      fear of being a burden on others is not only felt by those facing their imminent
      mortality, but also by older individuals who are currently healthy and living
      independently in the community. We also conclude that for some older people their
      prior experiences with health care and dying may be a strong factor in
      influencing and supporting medical practices that hasten death at the end of
      life. We believe it is crucial to understand the reasons why people support
      medical practices that hasten death well in advance of such practices ever
      becoming legally available.

PMID- 22864153
TI  - A retrospective review of notified human leptospirosis cases in the Waikato
      region of New Zealand, 2004 to 2010.
AB  - AIM: To retrospectively review notified human leptospirosis cases in the Waikato
      region of New Zealand between 2004 and 2010 and to identify risk factors for
      human leptospirosis infection. METHOD: Waikato leptospirosis notification data
      for the period 1 January 2004 to 31 December 2010 were analysed to identify any
      trends in the rates and distribution of key variables. RESULTS: Annual Waikato
      leptospirosis notification rates were consistently higher than national rates.
      Infection was associated with males (93%) of working age (97%) who had exposure
      to animals through their occupation. Most cases were employed in dry stock
      farming, dairy farming or in the meat processing industry. CONCLUSION: Those who
      work with cattle continue to be at risk of infection from Leptospira. The data
      suggests that dry stock cattle farmers are at the highest risk. It is speculated
      that the immunisation of all cattle herds may further reduce the incidence of
      leptospirosis, although more accurate collection of work exposure data and
      further analysis is needed to determine this.

PMID- 22864154
TI  - Phlebotomy patterns in haemochromatosis patients and their contribution to the
      blood supply.
AB  - AIMS: To determine venesection patterns in hereditary haemochromatosis (HC)
      patients in Christchurch, New Zealand, their contribution to the blood supply,
      and reasons for deferral. METHODS: Review of clinical records of 412 HC patients
      venesected by the NZ Blood Service at least once during 2009. RESULTS: Of 275
      males and 137 females, 384 had been tested for HFE gene mutations--76% were C282Y
      homozygotes, 12.8%, C282Y/H63D compound heterozygous, 8.6%, either H63D
      homozygotes, C282Y heterozygotes or H63D heterozygotes. Small numbers had no
      detectable mutations, were not iron overloaded but had been venesected for
      isolated hyperferritiniaemia. 53% were donors. C282Y homozygotes required
      significantly more venesections than patients of other genotypes. Eligible HC
      patients donated 3 units/donor/year compared to 1.63/person/year by healthy
      donors (p<0.001). HC patients contributed 3.4% of whole blood collections in
      2009. There were 212 permanent or temporary donation deferrals--common reasons
      were abnormal liver functions, chronic or malignant disease, or immigration from
      vCJD risk countries. CONCLUSIONS: HC donors donate at nearly twice the rate of
      healthy donors but contribute only a small amount to the blood pool. Revision of
      selection criteria may increase this contribution without compromising blood
      safety.

PMID- 22864155
TI  - Safety and efficacy of stroke thrombolysis at a secondary provincial hospital in
      New Zealand.
AB  - AIMS: Stroke thrombolysis with alteplase is the most effective therapy for acute
      ischaemic stroke. Most trial data comes from tertiary centres. This study set out
      to assess safety and efficacy of thrombolysis at a secondary provincial centre in
      New Zealand. METHODS: A retrospective 3-year audit was performed to assess
      efficacy and safety of altepase at a secondary provincial hospital in New
      Zealand. RESULTS: Out of 27 patients receiving treatment 17 (62.3%) improved and
      10 (37.0%) enjoyed essentially complete symptom resolution (mRS=0 or 1). There
      was one symptomatic intracranial haemorrhage (3.7%). CONCLUSION: Administration
      of intravenous alteplase for ischaemic stroke patients is effective and safe in
      the secondary provincial setting if local protocols are used, patient selection
      is stringent, and care is supervised by neurologists with training/experience in
      stroke care and thrombolysis. Aspects of thrombolysis-related management issues
      in this study population are discussed.

PMID- 22864156
TI  - New Zealand National Acute Stroke Services Audit: acute stroke care delivery in
      New Zealand.
AB  - AIMS: To audit the care of a consecutive group of acute stroke patients admitted
      to all District Health Boards (DHBs) in New Zealand. METHODS: A clinical audit
      involving a review of up to 40 consecutive stroke patients treated and discharged
      from each DHB between 1st of June 2008 and 31st of December 2008. RESULTS: The
      clinical care of 832 patients [400 men; median age 77 (interquartile range 67-84)
      years] admitted to 20 of 21 DHBs was audited. This represents approximately 20%
      of all stroke patients admitted to hospital in New Zealand over this 6 month
      period. Most of the audited patients were independent (66%, mRS=2) and 90% lived
      at home prior to their strokes. At stroke onset, 40% had a known diagnosis of
      atrial fibrillation (AF), of whom only 24% were taking anticoagulants. Thirty
      eight percent of patients arrived in hospital within 4.5 hours of stroke onset
      but only 3% were treated with stroke thrombolysis. Only 28% of patients were
      managed in a stroke unit but these patients had higher rates of thrombolysis,
      more rapid access to multidisciplinary team assessments and a lower rate of
      stroke progression (8% vs 15%, p<0.01). Only 21% of ischaemic stroke patients
      received aspirin within 48 hours and 35% of patients had a speech-language
      therapist assessment within 48 hours of admission. CONCLUSION: Access to stroke
      unit care and thrombolysis rates remain low in New Zealand and should be seen as
      the top priorities for acute stroke care improvement along with anticoagulation
      for stroke prevention in AF, acute aspirin use and increased speech language
      therapy assessments.

PMID- 22864157
TI  - New Zealand Malayan war veterans' exposure to dibutylphthalate is associated with
      an increased incidence of cryptorchidism, hypospadias and breast cancer in their
      children.
AB  - It is well known that the endocrine-disrupting chemical (EDC) dibutylphthalate
      (DBP) inhibits testosterone synthesis and can lead to feminisation in male
      laboratory animals. Moreover, it has long been speculated that human exposure
      would result in the similar effects, but this is difficult to study because
      specific human exposure cohorts are rare. We report increases in the incidences
      of hypospadias (p<0.05), cryptorchidism (p<0.05) and breast cancer (p<0.05) in
      the children of New Zealand soldiers who served in Malaya (1948-1960) and were
      exposed to DBP applied daily to their clothing as an acaricide to prevent tick
      transmitted bush typhus. In addition, we modelled absorption of DBP from the
      soldiers' clothing and using published data for skin absorption, and calculated a
      large theoretical absorbed dose of 64 mg/kg body weight/day which is similar to
      DBP's lowest observed adverse effect level (LOAEL) of 50 mg/kg body weight/day
      and thus indicates a biological effect is possible. This is the first report of a
      multigenerational developmental effect following DBP exposure in human males.

PMID- 22864158
TI  - Professionalism in its time and place: some implications for medical education.
AB  - Professionalism is fundamental to good medical practice but is multifaceted so
      observing that a person is professional in some areas will not guarantee that
      person would be professional in others. Most definitions of professionalism
      include a commitment to self-monitor and to improve; some personal virtues; and
      effective relationships with colleagues, patients and people who are important to
      those patients. In addition, it is suggested that expectations of professionalism
      may alter depending on context, both of time and place. Societal expectations
      relating to professionalism are likely to change over time and our expectations
      of individuals may alter according to the stage of training. The environment (the
      workplace, one's colleagues, the work tasks) is also highly influential on the
      manifestation of professional behaviours. The medical profession's social
      contract in relation to professionalism will always need to be updated. The
      effect of time and place means that searching for innate or stable elements of
      professionalism, in order to predict subsequent behaviours, is therefore
      difficult. This has implications for the selection, education and assessment of
      medical students. The focus should be on how to build adaptability and resilience
      to contextual influences; to identify those elements of professionalism that can
      be learnt; and build systems of assessment that reflect professionalism's
      multifaceted and contextual aspects.

PMID- 22864159
TI  - Asplenic fulminant sepsis secondary to a dog bite complicated by toxic epidermal
      necrolysis/Stevens-Johnson syndrome.
AB  - We report a case of asplenic fulminant sepsis in Australia following a dog bite
      which was complicated by toxic epidermal necrolysis/Stevens-Johnson syndrome
      (TENS/SJS). Capnocytophaga canimorsus, the infective organism, is a rare cause of
      septicaemia: a high degree of suspicion of this unusual organism and its early
      aggressive management is paramount. The diagnostic and management difficulties of
      TENS/SJS in the context of a patient with fulminant sepsis, DIC and on inotropes
      are also highlighted.

PMID- 22864160
TI  - Medical image. A rare tumour of the chest wall.

PMID- 22864161
TI  - PHARMAC looks great value for money--an Australian perspective.

PMID- 22864162
TI  - No need to ban smoking in cars with children present--it's almost snuffed out.

PMID- 22864165
TI  - Nanomedicine: Shake up the drug containers.

PMID- 22864163
TI  - High-throughput SNP discovery and genotyping for constructing a saturated linkage
      map of chickpea (Cicer arietinum L.).
AB  - The present study reports the large-scale discovery of genome-wide single
      nucleotide polymorphisms (SNPs) in chickpea, identified mainly through the next
      generation sequencing of two genotypes, i.e. Cicer arietinum ICC4958 and its wild
      progenitor C. reticulatum PI489777, parents of an inter-specific reference
      mapping population of chickpea. Development and validation of a high-throughput
      SNP genotyping assay based on Illumina's GoldenGate Genotyping Technology and its
      application in building a high-resolution genetic linkage map of chickpea is
      described for the first time. In this study, 1022 SNPs were identified, of which
      768 high-confidence SNPs were selected for designing the custom Oligo Pool All
      (CpOPA-I) for genotyping. Of these, 697 SNPs could be successfully used for
      genotyping, demonstrating a high success rate of 90.75%. Genotyping data of the
      697 SNPs were compiled along with those of 368 co-dominant markers mapped in an
      earlier study, and a saturated genetic linkage map of chickpea was constructed.
      One thousand and sixty-three markers were mapped onto eight linkage groups
      spanning 1808.7 cM (centiMorgans) with an average inter-marker distance of 1.70
      cM, thereby representing one of the most advanced maps of chickpea. The map was
      used for the synteny analysis of chickpea, which revealed a higher degree of
      synteny with the phylogenetically close Medicago than with soybean. The first set
      of validated SNPs and map resources developed in this study will not only
      facilitate QTL mapping, genome-wide association analysis and comparative mapping
      in legumes but also help anchor scaffolds arising out of the whole-genome
      sequencing of chickpea.

PMID- 22864166
TI  - Nanoelectronics: Nothing is like a vacuum.

PMID- 22864167
TI  - Environmental, health and safety issues: Incinerator filters nanoparticles.

PMID- 22864170
TI  - Bioleaching of chalcopyrite by defined mixed moderately thermophilic consortium
      including a marine acidophilic halotolerant bacterium.
AB  - A defined mixed moderately thermophilic consortium including three terrestrial
      microorganisms (Leptospirillum ferriphilum, Acidithiobacillus caldus and
      Ferroplasma thermophilum) and a marine acidophilic halotolerant bacterium
      (Sulfobacillus sp. TPY) was constructed to evaluate its ability for bioleaching
      of chalcopyrite with the addition of sodium chloride (NaCl), and the community
      dynamics was monitored by real-time quantitative PCR (qPCR). It was found that
      Sulfobacillus sp. TPY was able to tolerate 2% (w/v) NaCl, while other three
      microorganisms were suppressed when the concentration of NaCl was higher than
      0.35%. The results suggested that NaCl below certain concentration could improve
      copper extraction by using pure cultures or the consortium to bioleach
      chalcopyrite. Community dynamics analysis during bioleaching at 0.1% NaCl showed
      that Sulfobacillus sp. TPY was predominant species during the whole bioleaching
      process, L. ferriphilum and A. caldus were less at any time compared with
      Sulfobacillus sp. TPY. F. thermophilum had never been dominant species even in
      the final stage.

PMID- 22864169
TI  - Isolation of marine bacteria highly resistant to mercury and their
      bioaccumulation process.
AB  - The marine bacteria strains S1, S2 and S3, were isolated on seawater culturing
      medium containing Hg(2+), Cd(2+), Cr(6+) or Ni(2+) at concentrations of 20 mg L(
      1) and more. The isolates showed tolerance to these heavy metals. S1 grew in the
      presence of 120 mg L(-1) of Hg(2+) and accumulated Hg(2+) at pH 4-10. For the
      effect of co-existing cations on bioaccumulation of target metal, it was found
      that the effect depended on not only the variety and initial concentration of co
      existing ions, but also the initial concentration of target metal and biomass
      dosage. A new parameter, the ratio of remaining bioaccumulation capacity (RRBC)
      of biomass, was therefore defined to evaluate such effect. Furthermore, the
      mechanism evaluation revealed that S1 bound about 70% Hg(2+) on the cell surface,
      and carboxyl group played an important role in Hg(2+) binding.

PMID- 22864171
TI  - Production of cellulases by solid state fermentation with Aspergillus terreus and
      enzymatic hydrolysis of mild alkali-treated rice straw.
AB  - Rice straw was used as substrate for cellulase production by solid state
      fermentation with Aspergillus terreus. Substrate concentration, moisture ratio,
      inoculum size and initial pH were optimized using response surface methodology
      involving Box-Behnken design. The predicted filter paper activity under optimized
      parameters was 9.73 U/g and the validated filter paper activity was 10.96 U/g.
      Hydrolysis of the biomass pretreated with 0.125% to 1% NaOH for 24h at room
      temperature was performed using crude cellulase preparation. Treatment with 0.5%
      NaOH at room temperature for 24h was the most efficient treatment method for
      saccharification. Under the optimized conditions, rice straw yielded 676 mg
      reducing sugars per gram of substrate at a cellulase loading of 9 FPU g(-1)
      substrate. The present study establishes the possibility of using mild alkali
      pretreated rice straw for the production of fermentable sugars with 74.19%
      efficiency which can be further utilized for the production of ethanol.

PMID- 22864172
TI  - Nutrient transformations during composting of pig manure with bentonite.
AB  - This work aimed to evaluate the influence of different amounts of bentonite on
      nutrients transformation during pig manure composting process. The results showed
      that bentonite had no significant effects on compost temperature and pH changes.
      While, EC, moisture, OM, TN and NO(3)(-)-N were notably influenced by BT
      addition. The adding of BT could facilitate OM degradation, increase TKN content
      and decrease the C/N ratio. Increasing the proportion of bentonite in pig manure
      compost to reduce extractable heavy metal content is feasible. However, potherb
      mustard seed GI decreased with the proportion of added bentonite increasing. The
      results suggest that a proportion of less than 2.5% bentonite is recommended for
      addition to pig manure compost, and examining the additive ratio in a
      comprehensive waste composting project is a worthwhile direction for future
      research.

PMID- 22864173
TI  - Effects of lignin-derived phenolic compounds on xylitol production and key enzyme
      activities by a xylose utilizing yeast Candida athensensis SB18.
AB  - Candida athensensis SB18 is potential xylitol producing yeast isolated in
      Singapore. It has excellent xylose tolerance and is able to produce xylitol in
      high titer and yield. However, by-products, such as phenolic compounds, derived
      in lignocellulosic biomass hydrolysate might negatively influence the performance
      of this strain for xylitol production. In this work, four potential phenolic
      inhibitors, such as vanillin, syringaldehyde, 4-hydroxybenzaldehyde and phenol,
      were evaluated for their inhibitory effects on xylitol production by C.
      athensensis SB18. Phenol was shown to be the most toxic molecule on this
      microorganism followed by syringaldehyde. Vanillin and 4-hydroxylbenzaldehyde was
      less toxic than phenol and syringaldehyde, with vanillin being the least toxic.
      Inhibition was insignificant when the total content of inhibitors was below 1.0
      g/L. The presence of phenolic compounds affected the activity of xylose
      reductase, however not on that of xylitol dehydrogenase. C. athensensis SB18 is
      therefore a potential xylitol producer from hemicellulosic hydrolysate due to its
      assimilation of such phenolic inhibitors.

PMID- 22864174
TI  - Impact of Cr(VI) on P removal performance in enhanced biological phosphorus
      removal (EBPR) system based on the anaerobic and aerobic metabolism.
AB  - Influence of Cr(VI) on P removal in enhanced biological phosphorus removal (EBPR)
      system was investigated with respect to the composition of poly-phosphate
      accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), the
      transformation of poly-beta-hydroxyalkanoates (PHA) and glycogen, enzymes'
      activities, and the intracellular Cr. Whether EBPR system could revive after
      Cr(VI) shock was also explored. Results showed P removal performance was
      completely inhibited by Cr(VI) with the concentration more than 5 mg L(-1). PAOs
      were more sensitive to Cr(VI) than GAOs and the other bacteria were. PHA
      consumption, glycogen synthesis and adenylate kinase's activity had been
      inhibited by 5 mg L(-1) Cr(VI). Both adenylate kinase's activity and P removal
      efficiency were negatively correlated with the intracellular Cr. Recovery
      experiments revealed that P removal performance with 5 mg L(-1) Cr(VI) shock
      could revive after a 2-day recovery treatment, while systems with high level
      Cr(VI) (20 and 60 mg L(-1)) shock could not.

PMID- 22864175
TI  - Adsorption and desorption of copper(II) ions onto garden grass.
AB  - The garden grass (GG) was firstly used to remove copper(II) from water as
      bioadsorbent. From the results of characterisation, the GG had the merits of high
      specific surface area, significant adsorption sites and functional groups. Copper
      adsorption significantly depends on the initial copper concentrations, contact
      time, pH, adsorbent doses, particle sizes and temperature. The positive values of
      DeltaG degrees  indicates that the adsorption of copper onto garden grass is non
      spontaneous and values lies within the ranges of 4.452-13.660 kJ/mol for
      supporting physical adsorption. 0.1N H(2)SO(4) was found as suitable eluent,
      which could be used 5 cycles of adsorption-desorption. The data from adsorption
      and desorption equilibrium were well fitted by the Langmuir, SIPS and Redlich
      Peterson isotherm models. The maximum adsorption and desorption capacities were
      58.34 and 319.03 mg/g, respectively, for 1g dose. Adsorption and desorption
      kinetics could be described by the Pseudo-first-order model.

PMID- 22864176
TI  - The environmental sustainability of anaerobic digestion as a biomass valorization
      technology.
AB  - This paper studies the environmental sustainability of anaerobic digestion from
      three perspectives. First, reference electricity is compared to electricity
      production from domestic organic waste and energy crop digestion. Second,
      different digester feed possibilities in an agricultural context are studied.
      Third, the influence of applying digestate as fertilizer is investigated. Results
      highlight that biomass is converted at a rational exergy (energy) efficiency
      ranging from 15.3% (22.6) to 33.3% (36.0). From a life cycle perspective, a
      saving of over 90% resources is achieved in most categories when comparing
      biobased electricity to conventional electricity. However, operation without heat
      valorization results in 32% loss of this performance while using organic waste
      (domestic and agricultural residues) as feedstock avoids land resources. The use
      of digestate as a fertilizer is beneficial from a resource perspective, but
      causes increased nitrogen and methane emissions, which can be reduced by 50%,
      making anaerobic digestion an environmentally competitive bioenergy technology.

PMID- 22864177
TI  - Treatment of thin stillage in a high-rate anaerobic fluidized bed bioreactor
      (AFBR).
AB  - The primary objective of this work was to investigate the treatability of thin
      stillage as a by-product of bioethanol production plants using an anaerobic
      fluidized bed bioreactor (AFBR) employing zeolite with average diameter of (d(m))
      of 425-610 MUm and specific surface area (SSA) of 26.5m(2)/g as the carrier
      media. Despite the very high strength of thin stillage with chemical oxygen
      demand of 130,000 mg TCOD/L and suspended solids of 47,000 mg TSS/L, the AFBR
      showed up to 88% TCOD and 78% TSS removal at very high organic and solids loading
      rates (OLR and SLR) of 29 kg COD/m(3)d and 10.5 kg TSS/m(3)d respectively and
      hydraulic retention time (HRT) of 3.5 days. Methane production rates of up to 160
      L/d at the steady state equivalent to 40 L(CH4)/L(thin stillage)d and biogas
      production rate per reactor volume of 15.8L(gas)/L(reactor)d were achieved.

PMID- 22864178
TI  - Prediction of hydrogen sulphide production during anaerobic digestion of organic
      substrates.
AB  - The main objective of this study was to develop a methodology to predict the
      hydrogen sulphide content of raw biogas produced during anaerobic mono-digestion
      of a bioenergy feedstock. Detailed chemical and biological analyses were made on
      37 different feedstocks originating from urban wastewater treatment plants,
      farms, agri-food facilities and municipal wastes. Total sulphur content ranged
      from 1 to 29.6 mg S/kg of total solids, and 66% of the feedstocks analysed
      contained less than 5 mg S/kg of total solids. The biochemical methanogenic
      potential and biochemical biogas potential of each feedstock combined with its S
      content were used to predict appearance of H(2)S in the raw biogas. A model to
      link H(2)S in biogas with the carbon:sulphur ratio was established. Based on this
      model, a minimum carbon:sulphur ratio of 40 is required in feedstock to limit the
      concentration of hydrogen sulphide in raw biogas to less than 2% (volume/volume).

PMID- 22864179
TI  - Influence of omeprazole and famotidine on the antiplatelet effects of clopidogrel
      in addition to aspirin in patients with acute coronary syndromes: a prospective,
      randomized, multicenter study.
AB  - BACKGROUND: It remains unclear whether concomitant use of omeprazole attenuates
      platelet function as compared with that of famotidine in patients with acute
      coronary syndromes (ACS) who receive clopidogrel. METHODS AND RESULTS: In this
      prospective study, 130 ACS patients treated with aspirin and clopidogrel who
      underwent stent implantation were randomly assigned to receive a Japanese
      standard dose of omeprazole 10mg daily or famotidine 20mg daily for at least 4
      weeks. Between 14 and 28 days after enrollment, there was no significant
      difference in the platelet reactivity index (PRI) measured with vasodilator
      stimulated phosphoprotein phosphorylation assay between the omeprazole group
      (n=65) and famotidine group (n=65) (55+/-17% vs. 51+/-19%; P=0.26). The
      cumulative rate of adverse cardiovascular events at 12 months was similar in the
      groups (13% vs. 17%; P=0.81). The PRI was similar (54.9+/-17.9% vs. 54.0+/-17.8%;
      P=0.83) in the omeprazole group (n=33) and the famotidine group (n=39) among
      patients with ST-elevation myocardial infarction (STEMI). However, there was a
      trend toward a higher PRI (55.2+/-15.9% vs. 46.4+/-19.4%; P=0.06) in the
      omeprazole group (n=32) as compared with the famotidine group (n=26) among
      patients without persistent ST-segment elevation ACS. CONCLUSIONS: As compared
      with famotidine, concomitant use of low-dose omeprazole does not significantly
      attenuate the antiplatelet effects of clopidogrel in patients with ACS,
      especially in those with STEMI.

PMID- 22864180
TI  - Prognostic value of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid single
      photon emission computed tomography in diabetic patients with suspected ischemic
      heart disease.
AB  - BACKGROUND: Because of their high risk for cardiovascular events, we investigated
      the role of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) SPECT in
      evaluating the prognosis of diabetic patients with suspected coronary heart
      disease. METHODS AND RESULTS: We retrospectively registered 186 diabetic patients
      with suspected coronary heart disease, but no previous diagnosis of heart
      disease, who had been examined by BMIPP and thallium (TL) dual SPECT. They were
      followed for over 2 years. The dual SPECT images were scored to obtain summed
      defect scores for each SPECT image (BMDS, TLDS and mismatch score [MS]). The
      primary endpoint was the first incidence of all-cause cardiac events. The
      secondary endpoint was cardiac death. Clinical classical risk factors in addition
      to the stage of chronic kidney disease (CKD), as well as cardiac function, were
      included in the prognostic analysis. Cardiac events occurred in 39 patients,
      including 8 cardiac deaths. Kaplan-Meier analysis revealed significantly more
      frequent cardiac event rates in patients with than without MS >=5 or BMDS >=6
      (P<0.0001). Cox hazard multivariate analysis showed that MS and CKD stage or
      BMIPP and CKD stage were independent predictors. Only hemodialysis was a
      significant prognostic indicator for cardiac death. CONCLUSIONS: BMIPP SPECT when
      combined with CKD stage accurately predicts cardiac events among diabetic
      patients with suspected ischemic heart disease.

PMID- 22864181
TI  - Treatment planning of electroporation-based medical interventions:
      electrochemotherapy, gene electrotransfer and irreversible electroporation.
AB  - In recent years, cancer electrochemotherapy (ECT), gene electrotransfer for gene
      therapy and DNA vaccination (GET) and tissue ablation with irreversible
      electroporation (IRE) have all entered clinical practice. We present a method for
      a personalized treatment planning procedure for ECT, GET and IRE, based on
      medical image analysis, numerical modelling of electroporation and optimization
      with the genetic algorithm, and several visualization tools for treatment plan
      assessment. Each treatment plan provides the attending physician with optimal
      positions of electrodes in the body and electric pulse parameters for optimal
      electroporation of the target tissues. For the studied case of a deep-seated
      tumour, the optimal treatment plans for ECT and IRE require at least two
      electrodes to be inserted into the target tissue, thus lowering the necessary
      voltage for electroporation and limiting damage to the surrounding healthy
      tissue. In GET, it is necessary to place the electrodes outside the target tissue
      to prevent damage to target cells intended to express the transfected genes. The
      presented treatment planning procedure is a valuable tool for clinical and
      experimental use and evaluation of electroporation-based treatments.

PMID- 22864182
TI  - Integration of visual and proprioceptive afferents in kinesthesia.
AB  - Proprioceptive signals are of prime importance in kinesthesia. However, in
      conditions of visuo-proprioceptive conflicts, strong visual-evoked biases can be
      observed. In three experiments, we parsed the interaction between visual and
      proprioceptive afferents using the 'mirror box' paradigm. Participants' left arm,
      the image of which was reflected in a mirror, was passively moved into
      flexion/extension or remained static. In Experiment 1 proprioceptive afferents of
      the unseen static right arm were masked with diffuse arm vibration. In
      Experiments 2 and 3, afferent signals were enhanced by muscle vibration of biceps
      or triceps stretch receptors. Illusory arm movements were evaluated with
      subjective reports and matching adjustments. Results revealed that participants
      did not experience kinesthetic illusions when the mirror reflected the image of a
      static arm while proprioceptive afferents conveyed signals of a moving arm
      (Experiment 2). In this specific case, vision apparently contributed much more
      strongly to the final percept than proprioceptive signals. However, in most
      circumstances, the percept reflected integration of both afferent signals
      (Experiments 1-3). For instance, when both sensory channels conveyed signals of
      arm displacement but in the opposite direction, kinesthetic illusions occurred
      but were either proprioceptively (vibration illusion) or visually driven (mirror
      illusion), according to individual sensorial preferences (Experiments 2 and 3).
      These results indicate that kinesthesia is the product of cooperative integration
      processes in which the final percept strongly depends on the experimental
      conditions as well as sensorial preferences. The observed changes in the relative
      contribution of each input across experimental conditions likely reflect
      reliability-dependent weights.

PMID- 22864183
TI  - Neuroglobin of seals and whales: evidence for a divergent role in the diving
      brain.
AB  - Although many physiological adaptations of diving mammals have been reported,
      little is known about how their brains sustain the high demands for metabolic
      energy and thus O(2) when submerged. A recent study revealed in the deep-diving
      hooded seal (Cystophora cristata) a unique shift of the oxidative energy
      metabolism and neuroglobin, a respiratory protein that is involved in neuronal
      hypoxia tolerance, from neurons to astrocytes. Here we have investigated
      neuroglobin in another pinniped species, the harp seal (Pagophilus
      groenlandicus), and in two cetaceans, the harbor porpoise (Phocoena phocoena) and
      the minke whale (Balaenoptera acutorostrata). Neuroglobin sequences, expression
      levels and patterns were compared with those of terrestrial relatives, the ferret
      (Mustela putorius furo) and the cattle (Bos taurus), respectively. Neuroglobin
      sequences of whales and seals only differ in two or three amino acids from those
      of cattle and ferret, and are unlikely to confer functional differences, e.g. in
      O(2) affinity. Neuroglobin is expressed in the astrocytes also of P.
      groenlandicus, suggesting that the shift of neuroglobin and oxidative metabolism
      is a common adaptation in the brains of deep-diving phocid seals. In the cetacean
      brain neuroglobin resides in neurons, like in terrestrial mammals. However,
      neuroglobin mRNA expression levels were 4-15 times higher in the brains of harbor
      porpoises and minke whales than in terrestrial mammals or in seals. Thus
      neuroglobin appears to play a specific role in diving mammals, but seals and
      whales have evolved divergent strategies to cope with cerebral hypoxia. The
      specific function of neuroglobin that conveys hypoxia tolerance may either relate
      to oxygen supply or protection from reactive oxygen species. The different
      strategies in seals and whales resulted from a divergent evolution and an
      independent adaptation to diving.

PMID- 22864185
TI  - Adenosine receptor activation is responsible for prolonged depression of synaptic
      transmission after spreading depolarization in brain slices.
AB  - Spreading depolarization (SD) is a slowly propagating, coordinated depolarization
      of brain tissue, which is followed by a transient (5-10min) depression of
      synaptic activity. The mechanisms for synaptic depression after SD are
      incompletely understood. We examined the relative contributions of action
      potential failure and adenosine receptor activation to the suppression of evoked
      synaptic activity in murine brain slices. Focal micro-injection of potassium
      chloride (KCl) was used to induce SD and synaptic potentials were evoked by
      electrical stimulation of Schaffer collateral inputs to hippocampal area Cornu
      Ammonis area 1 (CA1). SD was accompanied by loss of both presynaptic action
      potentials (as assessed from fiber volleys) and field excitatory postsynaptic
      potentials (fEPSPs). Fiber volleys recovered rapidly upon neutralization of the
      extracellular direct current (DC) potential, whereas fEPSPs underwent a secondary
      suppression phase lasting several minutes. Paired-pulse ratio was elevated during
      the secondary suppression period, consistent with a presynaptic mechanism of
      synaptic depression. A transient increase in extracellular adenosine
      concentration was detected during the period of secondary suppression.
      Antagonists of adenosine A1 receptors (8-cyclopentyl-1,3-dipropylxanthine [DPCPX]
      or 8-cyclopentyl-1,3-dimethylxanthine [8-CPT]) greatly accelerated fEPSP recovery
      and abolished increases in paired-pulse ratio normally observed after SD. The
      duration of fEPSP suppression was correlated with both the duration of the DC
      shift and the area of tissue depolarized, consistent with the model that
      adenosine accumulates in proportion to the metabolic burden of SD. These results
      suggest that in brain slices, the duration of the DC shift approximately defined
      the period of action potential failure, but the secondary depression of evoked
      responses was in large part due to endogenous adenosine accumulation after SD.

PMID- 22864186
TI  - Purkinje cell loss and motor coordination defects in profilin1 mutant mice.
AB  - Profilin1 is an actin monomer-binding protein, essential for cytoskeletal
      dynamics. Based on its broad expression in the brain and the localization at
      excitatory synapses (hippocampal CA3-CA1 synapse, cerebellar parallel fiber (PF)
      Purkinje cell (PC) synapse), an important role for profilin1 in brain development
      and synapse physiology has been postulated. We recently showed normal physiology
      of hippocampal CA3-CA1 synapses in the absence of profilin1, but impaired glial
      cell binding and radial migration of cerebellar granule neurons (CGNs).
      Consequently, brain-specific inactivation of profilin1 by exploiting conditional
      mutants and Nestin-mediated cre expression resulted in a cerebellar hypoplasia,
      aberrant organization of cerebellar cortex layers, and ectopic CGNs. Apart from
      these findings we noted a loss of PCs and an irregularly shaped PC layer in adult
      mutants. In this study, we show that PC migration and development are not
      affected in profilin1 mutants, suggesting cell type-specific functions for
      profilin1 in PCs and CGNs. PC loss begins during the second postnatal week and
      progresses until adulthood with no further impairment in aged mutants. In Nestin
      cre profilin1 mutants, defects in cerebellar cortex cytoarchitecture are
      associated with impaired motor coordination. However, in L7-cre mutants, lacking
      profilin1 specifically in PCs, the cerebellar cortex cytoarchitecture is
      unchanged. Thereby, our results demonstrate that the loss of PCs is not caused by
      cell-autonomous defects, but presumably by impaired CGN migration. Finally, we
      show normal functionality of PF-PC synapses in the absence of profilin1. In
      summary, we conclude that profilin1 is crucially important for brain development,
      but dispensable for the physiology of excitatory synapses.

PMID- 22864184
TI  - Vestibular responses in the macaque pedunculopontine nucleus and central
      mesencephalic reticular formation.
AB  - The pedunculopontine nucleus (PPN) and central mesencephalic reticular formation
      (cMRF) both send projections and receive input from areas with known vestibular
      responses. Noting their connections with the basal ganglia, the locomotor
      disturbances that occur following lesions of the PPN or cMRF, and the encouraging
      results of PPN deep brain stimulation in Parkinson's disease patients, both the
      PPN and cMRF have been linked to motor control. In order to determine the
      existence of and characterize vestibular responses in the PPN and cMRF, we
      recorded single neurons from both structures during vertical and horizontal
      rotation, translation, and visual pursuit stimuli. The majority of PPN cells
      (72.5%) were vestibular-only (VO) cells that responded exclusively to rotation
      and translation stimuli but not visual pursuit. Visual pursuit responses were
      much more prevalent in the cMRF (57.1%) though close to half of cMRF cells were
      VO cells (41.1%). Directional preferences also differed between the PPN, which
      was preferentially modulated during nose-down pitch, and cMRF, which was
      preferentially modulated during ipsilateral yaw rotation. Finally, amplitude
      responses were similar between the PPN and cMRF during rotation and pursuit
      stimuli, but PPN responses to translation were of higher amplitude than cMRF
      responses. Taken together with their connections to the vestibular circuit, these
      results implicate the PPN and cMRF in the processing of vestibular stimuli and
      suggest important roles for both in responding to motion perturbations like falls
      and turns.

PMID- 22864188
TI  - DNA commission of the International Society of Forensic Genetics: Recommendations
      on the evaluation of STR typing results that may include drop-out and/or drop-in
      using probabilistic methods.
AB  - DNA profiling of biological material from scenes of crimes is often complicated
      because the amount of DNA is limited and the quality of the DNA may be
      compromised. Furthermore, the sensitivity of STR typing kits has been
      continuously improved to detect low level DNA traces. This may lead to (1)
      partial DNA profiles and (2) detection of additional alleles. There are two key
      phenomena to consider: allelic or locus 'drop-out', i.e. 'missing' alleles at one
      or more genetic loci, while 'drop-in' may explain alleles in the DNA profile that
      are additional to the assumed main contributor(s). The drop-in phenomenon is
      restricted to 1 or 2 alleles per profile. If multiple alleles are observed at
      more than two loci then these are considered as alleles from an extra contributor
      and analysis can proceed as a mixture of two or more contributors. Here, we give
      recommendations on how to estimate probabilities considering drop-out, Pr(D), and
      drop-in, Pr(C). For reasons of clarity, we have deliberately restricted the
      current recommendations considering drop-out and/or drop-in at only one locus.
      Furthermore, we offer recommendations on how to use Pr(D) and Pr(C) with the
      likelihood ratio principles that are generally recommended by the International
      Society of Forensic Genetics (ISFG) as measure of the weight of the evidence in
      forensic genetics. Examples of calculations are included. An Excel spreadsheet is
      provided so that scientists and laboratories may explore the models and input
      their own data.

PMID- 22864189
TI  - Scope and standards for wound, ostomy and continence specialty practice nursing:
      a white paper from the WOCN Society.

PMID- 22864187
TI  - Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients
      undergoing liver transplantation.
AB  - For many cancers, features of the metabolic syndrome, such as diabetes and
      obesity, have been associated with both increased risk of cancer development and
      poor outcomes. METHODS: We examined a large retrospective cohort of 342
      consecutive patients who underwent liver transplantation for hepatocellular
      carcinoma between January 1999 and July 2010 at our institution. We evaluated the
      relationship between diabetes, obesity, hepatocellular carcinoma (HCC)
      recurrence, and overall survival. RESULTS: We found that a body mass index (BMI)
      higher than 30 was an independent predictor of poor overall survival in a
      multivariable Cox model, approximately doubling the risk of death after
      transplantation. A BMI higher than 30 was also a predictor of recurrent HCC,
      although this was of borderline statistical significance (hazard ratio for
      recurrence, 1.9; 95% confidence interval, 0.9-4.1). We also found increased BMI
      to be an independent predictor of microvascular invasion within HCC tumors,
      lending a possible explanation to these results. Those with diabetes showed
      worsened overall survival compared with those without diabetes in univariate but
      not multivariable analysis, possibly related to longer wait times. CONCLUSIONS:
      Our findings suggest a relationship between higher BMI, tumor vascular invasion,
      increased recurrence, and worsened overall survival. These findings may help
      explain why those with high BMI have worse outcomes from their cancers. A better
      understanding of the role of obesity and diabetes in patients with cancer should
      help develop better predictors of outcome and improved treatment options for
      patients with HCC.

PMID- 22864190
TI  - Implementing a continuous quality improvement program for reducing pressure
      prevalence in a teaching hospital in China.
AB  - PURPOSE: The purpose of this study was to determine whether a continuous quality
      improvement program would reduce pressure ulcer prevalence. SUBJECTS AND SETTING:
      The study sample comprised 2913 patients who were used as a baseline comparison
      group and 3019 patients who acted as the intervention group. The research setting
      was a 3000-bed teaching hospital with 61 nursing units located in Wuhan, China.
      DESIGN: This prospective study compared pressure ulcer prevalence of patients
      admitted to hospital before and after implementation of a continuous quality
      improvement program designed to reduce the incidence of hospital-acquired
      pressure ulcers. The program was implemented after baseline data were collected
      in April and the comparison prevalence survey was completed in October of the
      same year. Pressure ulcer prevalence data were collected on a single day.
      RESULTS: The overall pressure ulcer prevalence (combining ulcers that were
      hospital acquired and present on admission) was 1.8% at baseline as compared to
      1.4% following implementation of the quality improvement program. The prevalence
      of hospital-acquired pressure ulcers was 1.5% at baseline; it was 1.1% following
      the intervention. Excluding stage 1 pressure ulcers, the prevalence was 0.8% and
      0.6%, respectively. No stage 4 pressure ulcers were identified when prevalence
      was measured after initiation of the prevention project. CONCLUSION: Pressure
      ulcer prevalence, which was low at baseline measurement, did not statistically
      significantly decrease, despite a comprehensive quality improvement program.

PMID- 22864191
TI  - Diabetes mellitus as a risk factor for surgery-related pressure ulcers: a meta
      analysis.
AB  - PURPOSE: The purpose of this study was to determine whether diabetes mellitus is
      associated with increased likelihood of surgery-related (perioperative) pressure
      ulcers. METHODS: The MEDLINE and Thomson Reuters Web of Knowledge electronic
      databases were searched for studies of diabetes as a risk factor for surgery
      related pressure ulcers in case-control or cohort design; studies were limited to
      those published in English. Data from studies meeting inclusion criteria were
      pooled, and a meta-analysis was completed using the meta-analysis of
      observational studies in epidemiology (MOOSE) guidelines. Odds ratios for surgery
      related pressure ulcers were calculated for patients with and without diabetes
      mellitus. RESULTS: Six observational studies were identified involving a total of
      2453 patients. When compared to patients with normal glucose tolerance, persons
      with diabetes mellitus were more likely to experience surgery-related pressure
      ulcers (odds ratio = 2.15; 95% confidence interval: 1.62-2.84). CONCLUSION: Our
      meta-analysis indicates that patients with diabetes mellitus are slightly more
      than twice as likely to develop surgery-related pressure ulcers as compared to
      patients with normal glucose tolerance.

PMID- 22864192
TI  - Use of high-frequency ultrasound to detect heel pressure injury in elders.
AB  - PURPOSE: To examine the usefulness of high-frequency ultrasound (HFU) to detect
      heel pressure injury in geriatric medical patients, to compare the prevalence
      rates of visualized pressure ulcers with the prevalence of hidden injury, and to
      determine whether HFU could assist in predicting the development of heel pressure
      injury. SUBJECTS AND SETTING: The sample comprised 100 medical patients who were
      aged 65 years or older, had a Braden Scale score of 10 to 17, and remained
      hospitalized 28 days or less. Participants had at least 1 heel free of visible
      pressure injury. The study setting was a 528-bed urban hospital in the
      northeastern United States. METHODS: The study used a prospective, descriptive,
      observational design for data collection. At the initial visit, chart review and
      physical examination were used to obtain data about pressure ulcer risk factors,
      and heels were assessed visually and with HFU. Subsequent visits included visual
      and scan evaluations for pressure injury. Patients in the study were seen at
      least twice; 82 were assessed 3 times and 43 were assessed 4 times. RESULTS: The
      prevalence rate of visible heel pressure ulcers was 7.3% for 520 patients who met
      inclusion criteria. Slightly more than one-tenth (10.1%) of subjects without heel
      ulcers had 2 normal heels scans upon entry into the study. Age, Braden Scale
      score, foot temperature, edema, and turgor were not statistically significant
      predictors of abnormal heel scans. However, there was a statistically significant
      relationship between low friction/shear scores and abnormal heel scans,
      particularly in relation to the right foot. CONCLUSIONS: High-frequency
      ultrasound detected occult injury more than visual assessment, but scans are not
      easy to interpret in heels due to calluses and other skin changes. It appears
      that patients have a greater tendency for pressure injury on the right heel than
      on the left heel and risk may be predicted by low friction/shear scores.

PMID- 22864193
TI  - Growth and development issues in adolescents with ostomies: a primer for the WOC
      nurses.
AB  - Caring for the adolescent (13-18 years of age) with an ostomy presents multiple
      challenges. The purpose of this article is to provide strategies to assist the
      WOC nurse in minimizing the potential impact on growth and development for this
      age group with an ostomy. This is relevant to the WOC nurse since it is estimated
      that between 6% and 14% of all adolescents have symptoms of irritable bowel
      disease, and many will require an ostomy. Thus the WOC nurse will be called upon
      to provide care to this age group. This article discusses normal adolescent
      growth and development and provides strategies to support the normal growth and
      development.

PMID- 22864194
TI  - The effects of urinary incontinence on sexuality: seeking an intimate
      partnership.
AB  - PURPOSE: The purpose of this study was to investigate the impact of urinary
      incontinence (UI) on sexuality and intimate relationships. SUBJECTS AND SETTING:
      Thirty-two problem-centered interviews were conducted with 22 community-dwelling
      women and 10 men between 38 and 83 years of age. Their mean age was 54.8 years;
      their age range was 38 to 83 years. Interviews were primarily conducted in
      participants' homes across Germany. METHODS: A qualitative design, based on the
      Grounded Theory method, was used for data collection. RESULTS: Urinary
      incontinence influenced 4 important areas: (1) sexuality, (2) existing
      partnerships, (3) new partnerships, and (4) the search for professional help.
      Participants reported that a part of their male or female identity was lost. In
      some cases, UI led to separation, which was experienced as very hurtful for
      participants and had negative impact on the search for a new partnership. While
      some persons developed strategies to enjoy a fulfilling sexual life despite
      incontinence, others gave up hope of finding sexual intimacy. The participants in
      this study rarely felt understood or supported by health care professionals.
      CONCLUSIONS: Participants reported that UI resulted in changes in their sex life
      that affected both them and their partners. Some participants reported that part
      of their male or female identity had been lost because of restrictions in sexual
      activities imposed by urine loss.

PMID- 22864195
TI  - Defect chemistry of a BaZrO3 Sigma3 (111) grain boundary by first principles
      calculations and space-charge theory.
AB  - Defect calculations from density functional theory are implemented with space
      charge theory models to describe the equilibrium defect chemistry of a Sigma3
      (111) symmetric tilt boundary in BaZrO(3). As such, the space-charge potential
      and the concentrations of , , , NH and  in the bulk, core and space-charge
      regions of the interface are calculated as a function of temperature and
      atmospheric conditions. Our results show that the core will be predominated by 
      under hydrating conditions and that the space-charge potential increases with
      water vapor pressure. Under nitriding conditions, , NH and  will predominate the
      core in different temperature regimes and effects of these defects on the space
      charge properties are discussed.

PMID- 22864196
TI  - Unexpected thermal decomposition of the "Alder carbene" (iPr2N)2C.
AB  - The "Alder carbene" (iPr(2)N)(2)C undergoes a beta-fragmentation in solution
      already at room temperature, affording propene and N,N,N'
      triisopropylformamidine. This stands in sharp contrast to the indefinite
      stability previously claimed for this iconic compound.

PMID- 22864198
TI  - Measuring substrate binding and affinity of purified membrane transport proteins
      using the scintillation proximity assay.
AB  - The scintillation proximity assay (SPA) is a rapid radioligand binding assay.
      Upon binding of radioactively labeled ligands (here L-[(3)H]arginine or D
      [(3)H]glucose) to acceptor proteins immobilized on fluoromicrospheres (containing
      the scintillant), a light signal is stimulated and measured. The application of
      SPA to purified, detergent-solubilized membrane transport proteins allows
      substrate-binding properties to be assessed (e.g., substrate specificity and
      affinity), usually within 1 d. Notably, the SPA makes it possible to study
      specific transporters without interference from other cellular components, such
      as endogenous transporters. Reconstitution of the target transporter into
      proteoliposomes is not required. The SPA procedure allows high sample throughput
      and simple sample handling without the need for washing or separation steps:
      components are mixed in one well and the signal is measured directly after
      incubation. Therefore, the SPA is an excellent tool for high-throughput screening
      experiments, e.g., to search for substrates and inhibitors, and it has also
      recently become an attractive tool for drug discovery.

PMID- 22864199
TI  - Whole plant cell wall characterization using solution-state 2D NMR.
AB  - Recent advances in nuclear magnetic resonance (NMR) technology have made it
      possible to rapidly screen plant material and discern whole cell wall information
      without the need to deconstruct and fractionate the plant cell wall. This
      approach can be used to improve our understanding of the biology of cell wall
      structure and biosynthesis, and as a tool to select plant material for the most
      appropriate industrial applications. This is particularly true in an era when
      renewable materials are vital to the emerging bio-based economies. This protocol
      describes procedures for (i) the preparation and extraction of a biological plant
      tissue, (ii) solubilization strategies for plant material of varying composition
      and (iii) 2D NMR acquisition (for typically 15 min-5 h) and integration methods
      used to elucidate lignin subunit composition and lignin interunit linkage
      distribution, as well as cell wall polysaccharide profiling. Furthermore, we
      present data that demonstrate the utility of this new NMR whole cell wall
      characterization procedure with a variety of degradative methods traditionally
      used for cell wall compositional analysis.

PMID- 22864200
TI  - Determining the polysaccharide composition of plant cell walls.
AB  - The plant cell wall is a chemically complex structure composed mostly of
      polysaccharides. Detailed analyses of these cell wall polysaccharides are
      essential for our understanding of plant development and for our use of plant
      biomass (largely wall material) in the food, agriculture, fabric, timber, biofuel
      and biocomposite industries. We present analytical techniques not only to define
      the fine chemical structures of individual cell wall polysaccharides but also to
      estimate the overall polysaccharide composition of cell wall preparations. The
      procedure covers the preparation of cell walls, together with gas chromatography
      mass spectrometry (GC-MS)-based methods, for both the analysis of monosaccharides
      as their volatile alditol acetate derivatives and for methylation analysis to
      determine linkage positions between monosaccharide residues as their volatile
      partially methylated alditol acetate derivatives. Analysis time will vary
      depending on both the method used and the tissue type, and ranges from 2 d for a
      simple neutral sugar composition to 2 weeks for a carboxyl reduction/methylation
      linkage analysis.

PMID- 22864201
TI  - Effect of warm air-drying on dentin bond strength of single-step self-etch
      adhesives.
AB  - The effect of warm air-drying on the dentin bond strengths of the single-step
      self-etch adhesives was determined. The adhesives were applied to bovine dentin
      followed by drying in a stream of warm air for 5, 10, and 15 s at 37 degrees C.
      Resin composites were condensed into a mold and polymerized. Specimens were
      stored in distilled water at 37 degrees C for 24 h, then shear tested. The
      surface free-energies were determined by measuring the contact angles of three
      test liquids placed on the cured adhesives. The dentin bond strengths varied
      according to the air-drying time. The value of the acid component increased
      slightly when drying was performed with a stream of warm air, whereas that of the
      base component decreased significantly. These data suggested that warm air-drying
      was essential to obtain adequate bond strengths, although increasing the drying
      time did not significantly influence the bond strength.

PMID- 22864202
TI  - Fracture resistance of direct inlay-retained adhesive bridges: effect of pontic
      material and occlusal morphology.
AB  - This study evaluated the effect of a) pontic materials and b) occlusal
      morphologies on the fracture resistance of fi ber-reinforced composite (FRC)
      inlay-retained fixed dental prostheses (FDP). Inlay-retained FRC FPDs (N=45, n=9)
      were constructed using a) resin composite (deep anatomy), b) natural tooth, c)
      acrylic denture tooth, d) porcelain denture tooth and e) resin composite (shallow
      anatomy), as pontic materials. In addition resin composite beams were fabricated
      (N=30, n=10): i) 'circular', ii) 'elliptic I', and iii) 'elliptic II'. There was
      no significant difference between the fracture resistance of Groups a, b, c, and
      d (598, 543, 539, 509 N, respectively) (p>0.05) (One-way ANOVA). Fracture
      resistance of Group e (1,186 N) was significantly higher than those of other
      groups (p<0.05) (Tukey's test). No significant difference was found between Group
      i (1,750 N) and Group ii (1,790 N). Not the pontic material but the occlusal
      morphology affects the fracture resistance of FRC FDPs.

PMID- 22864203
TI  - Filler size of resin-composites, percentage of voids and fracture toughness: is
      there a correlation?
AB  - The objective of this study was to investigate the correlation between filler
      size, fracture toughness and voids. Seven model resin composites and one
      commercial have been used in the study. A single edge notch mould was used to
      prepare samples (n=8). A selected area of 1mm below and above the notch was
      scanned with micro CT and then the percentage of voids calculated. A universal
      testing machine was used to measure fracture toughness. Percentage of voids and
      fracture toughness data were analysed using ANOVA and post hoc methods were
      performed to check any significant differences between materials tested (p<0.05).
      CONCLUSION: Filler size is strongly correlated to % voids but has no effect on
      fracture toughness.

PMID- 22864204
TI  - Resistance to fracture of roots filled with different sealers.
AB  - The aim of this study was to compare the fracture resistance of roots filled with
      gutta percha (GP) and different root canal sealers.Fifty-five human maxillary
      central incisors were selected and randomly divided into three experimental
      groups (Groups 1-3) and two control groups (Groups 4 and 5). They were Group 1-15
      root canals filled with an epoxy resin-based sealer (AH Plus) and GP, Group 2 -15
      root canals filled with a calcium silicate-based sealer (iRoot SP) and GP, Group
      3: 15 root canals filled with another calcium silicate-based sealer (MTA
      Fillapex) and GP, Group 4: five roots were instrumented but not filled, and Group
      5: five roots were neither instrumented nor filled. Compressive loading was
      carried out using a universal testing machine until fracture occurred. Force
      applied at time of fracture was recorded as fracture strength of specimen in
      Newtons. There were no significant differences in fracture strength among the
      three experimental groups (p>0.05), whose results were significantly superior to
      that of Group 4 (p<0.05). In conclusion, all the root canal sealers used in the
      present study increased the fracture resistance of instrumented root canals.

PMID- 22864205
TI  - An approach to normalizing micro-CT depth profiles of mineral density for
      monitoring enamel remineralization progress.
AB  - To indicate the possibility of a new approach to creating mineral density
      profiles, and to examine longitudinal changes in 'the rate of remineralization
      (RA)' and 'the mineral density (DAs) at 4 different depths' (surface zone: SZ,
      lesion body: LB, middle zone: MZ, deep zone near to sound area: DZ) in enamel
      subsurface lesions, eight demineralized bovine enamel-dentin blocks were
      remineralized for 1 to 4 week and investigated using Micro-focus X-ray CT (micro
      CT). After CT scanning, mineral density profiles were created.Mineral densities
      at each depth after demineralization were SZ is approximately equal to LB<MZ<DZ.
      Increase in RA was the greatest in the first week of remineralization and it
      decreased over time. Increments of the mineral density were greater in the order
      of SZ is approximately equal to LB>MZ>DZ. This study indicated a new approach to
      create a mineral density profile and suggested the greater the value of the
      mineral density before the remineralization, the smaller the mineral density
      increments.

PMID- 22864206
TI  - Relation between incremental lines and tensile strength of coronal dentin.
AB  - In one aspect, this study examined the tensile strength of coronal dentin, as a
      function of the location of incremental lines, in two types of teeth: human molar
      versus bovine incisor. In another aspect, tensile strength in coronal dentin was
      examined with tensile loading in two different orientations to the incremental
      lines: parallel versus perpendicular. There were four experimental groups in this
      study: HPa, human molar dentin with tensile orientation parallel to the
      incremental lines; HPe, human molar dentin with tensile orientation perpendicular
      to the incremental lines; BPa, bovine incisor dentin with tensile orientation
      parallel to the incremental lines; BPe, bovine incisor dentin with tensile
      orientation perpendicular to the incremental lines. Tensile strengths of the
      parallel group (HPa and BPa) were significantly higher (p<0.05) than those of the
      perpendicular group (HPe and BPe). Effect of structural anisotropy, contributed
      by the incremental lines, was thus confirmed in coronal dentin. However, there
      were no differences in anisotropy effect between the two tooth types.

PMID- 22864207
TI  - Fabrication of solid and hollow carbonate apatite microspheres as bone
      substitutes using calcite microspheres as a precursor.
AB  - Spherical carbonate apatite (CO3Ap) microspheres approximately 1 mm in diameter
      were fabricated by granulation of calcium hydroxide around a core followed by
      carbonation and phosphatization through dissolution-precipitation reaction. CO3Ap
      microspheres with high uniformity could not be achieved without using a core.
      Solid CO3Ap microspheres were obtained using a calcite core whereas hollow CO3Ap
      microspheres were obtained using a NaCl core. The obtained microsphere was
      identified as B-type CO3Ap by Fourier transform infrared analysis and the
      carbonate content was approximately 7-8 wt% regardless of the type of core used
      for sample preparation. The mechanical strength of both the solid and hollow
      CO3Ap microspheres was sufficient for practical use as a bone substitute.

PMID- 22864209
TI  - Effect of (-)-epigallocatechin gallate on electrochemical behavior and surface
      film composition of Co-Cr alloy used in dental restorations.
AB  - The aim of this study was to investigate the electrochemical behavior of Co-Cr
      alloy in artificial saliva containing (-)-epigallocatechin gallate (EGCG) and to
      characterize the composition and structure of the passive film formed by
      potentiodynamic polarization.Electrochemical measurements ranked the corrosion
      resistance of Co-Cr dental cast alloy as follows when exposed to artificial
      saliva containing different concentrations of EGCG: 4.0 g/L<2.0 g/L<0 g/L<0.5
      g/L<1.0 g/L. This showed that the concentration of EGCG in artificial saliva
      affected the corrosion behavior of Co-Cr alloy. X-ray photoelectron spectroscopy
      (XPS) results revealed that the outermost surface layer on Co-Cr alloy was mainly
      composed of Cr2O3 and EGCG-Cr (III) ion complex, which were formed by redox and
      complex formation reactions respectively. When the redox reaction was dominant,
      Co-Cr alloy exhibited high corrosion resistance in EGCG-containing artificial
      saliva. On the contrary, when the complex formation reaction was dominant, Co-Cr
      alloy exhibited low corrosion resistance.

PMID- 22864208
TI  - Effect of air-drying dentin surfaces on dentin bond strength of a solvent-free
      one-step adhesive.
AB  - The purpose was to evaluate the effect of air-drying dentin surfaces on the
      microtensile bond strength (MUTBS) of a solvent-free onestep adhesive (Bond 1
      SF). Twelve human molars were ground with 600-grit SiC paper. Before applying
      bonding agent, the dentin surface was rinsed with distilled water and blot-dried
      with tissue paper, followed by air-drying for 0, 3, 30, and 60 s using with a
      dental air syringe. After applying and curing Bond 1 SF, resin composite was
      incrementally built up. Specimens were then stored in distilled water for 24 h
      and then MUTBSs were measured at a cross-head speed of 1 mm/min. Higher MUTBS
      were observed when the dentin surface was air-dried for 3 s (33.2+/-6.8MPa)>0 s
      (26.7+/-4.5MPa)>30 s (22.6+/-5.5MPa)=60 s (20.4+/-5.0MPa). The results suggested
      that prolonged air-drying of the dentin surface removed water and decreased the
      bond strengths of Bond 1 SF.

PMID- 22864210
TI  - Effects of different luting cements and light curing units on the sealing ability
      and bond strength of fiber posts.
AB  - This study evaluated the sealing ability and push-out bond strength of two luting
      cements cured with two different types of light curing units (LCU): light
      emitting diode (LED) versus quartz tungsten halogen (QTH). Forty teeth were
      divided into four groups(n=10/group). Quartz fiber posts (D. T. Light-Post) were
      luted to coronal or apical section of root canals using two types of resin
      cements (Panavia F or RelyX) cured with either LED LCU (Elipar FreeLight II) or
      QTH LCU (Optilux 501). Highest push-out bond strength was exhibited by QTH-cured
      RelyX, which was not significantly different from LED-cured RelyX but was higher
      than QTH-cured Panavia F. The push-out bond strength of Panavia F did not differ
      with LCU type (p>0.05), but exhibited lower values than both QTH- and LED-cured
      RelyX. Fluid filtration test revealed that sealing ability was not influenced by
      luting cement type, but was significantly influenced by LCU type in favor of QTH
      light source: QTH-cured specimens displayed better seal than LED-cured ones
      (p<0.05).

PMID- 22864211
TI  - Tissue response to experimental dental cements prepared from a modified powder
      glass composition.
AB  - The present work seeks to evaluate the biocompatibility of experimental glass
      ionomer cements (GIC) prepared from niobium-calcium fluoro-alumino-silicate glass
      powder and two commercial GICs. The GICs were implanted into the subcutaneous
      connective tissue of sixty rats. The rats were sacrificed during four varying
      time periods: 7, 15, 30, and 60 days and histopathological examinations were then
      performed. The Kruskal-Wallis test was performed to evaluate any significant
      differences between the materials. Additionally, multiple comparisons of the mean
      rank were also carried out using the Dunn test (p<0.05). No significant
      differences were observed that one GIC was superior to the other. The tissue
      response for all of the GICs tested was similar in all the periods examined.

PMID- 22864212
TI  - Fabrication of microporous calcite block from calcium hydroxide compact under
      carbon dioxide atmosphere at high temperature.
AB  - Effects of carbonation temperature and compacting pressure on basic properties of
      calcite block were studied using Ca(OH)2 compact made with 0.2-2.0 MPa and their
      carbonation at 200-800oC for 1 h. Microporous calcite was obtained only when
      carbonated at 600oC using Ca(OH)2 compact made with 0.2 MPa even though
      thermogravimetry analysis showed that calcite powder was stable up to 920oC under
      CO2 atmosphere. CaO formed by carbonation at 700oC and 800oC is thought to be
      caused by the limited CO2 diffusion interior to the Ca(OH)2 compact. Also,
      unreacted Ca(OH)2 was found for Ca(OH)2 compact prepared with 0.5 MPa or higher
      pressure even when carbonated at 600oC. As a result of high temperature
      carbonation, crystallite size of the calcite, 58.0 nm, was significantly larger
      when compared to that of calcite prepared at room temperature, 35.5 nm. Porosity
      and diametral tensile strength of the microporous calcite were 39.5% and 6.4 MPa.

PMID- 22864213
TI  - Multifactorial analysis of the impact of different manufacturing processes on the
      marginal fit of zirconia copings.
AB  - This study evaluated the effect of different parameters on the marginal precision
      of CAD/CAM-fabricated zirconia copings. Specimens(n=60) were fabricated with two
      different scanners and two milling systems. The copings were evaluated with
      respect to their mean and average maximum marginal gaps. A two-way analysis of
      variance (ANOVA) (alpha=0.05) was used to evaluate the effect of different
      parameters (scanner, milling process) on marginal accuracy. The mean (averaged
      maximum) marginal gaps ranged from 57.9 (112.2 MUm) to 71.0 (144.6 MUm) in the
      "as machined" state. After manual adaptation, the respective values ranged from
      54.6 (98.0 MUm) to 59.9(107.7 MUm). The system and manual adaptation variables
      were found both to have multiple significant effects on the marginal gap size and
      to have a complex interaction. Thus, synchronized/validated processing chains
      should be preferentially used to guarantee optimal fitting accuracy for CAD/CAM
      zirconia restorations.

PMID- 22864214
TI  - Effects of silane coupling agents and solutions of different polarity on PMMA
      bonding to alumina.
AB  - The objective of this study was to clarify the effects of silane coupling agents
      and solutions of different polarity on polymethyl methacrylate (PMMA) bonding to
      alumina. Three silane coupling agents (3-methacryloxypropyltrimethoxysilane
      (MPS),3-aminopropyltriethoxysilane (APS) and N-2 (aminoethyl) 3
      aminopropyltriethoxysilane) and 3 different polar solutions, 70% ethanol,
      isopropanol and toluene, were selected for silanization. Shear bond strengths
      were statistically compared with Tukey HSD(alpha=0.05). The alumina surfaces
      after silanization and shear bond test were examined with an energy dispersive
      spectrometer (EDS).The bond strengths of PMMA on the alumina with MPS (15.0 MPa),
      APS (13.8 MPa) in ethanol were greater than the others in nonthermocyclings. The
      bond strength decreased after thermocyclings. The ethanol groups were greater
      than the others. EDS revealed Si remaining on the alumina surface after the shear
      bond test. The results indicated that the silanization using MPS and APS with
      ethanol solution was effective.

PMID- 22864215
TI  - A study on the sealing ability and antibacterial activity of Ca3SiO5/CaCl2
      composite cement for dental applications.
AB  - The objective of this study was to evaluate the sealing ability and antibacterial
      activity of Ca3SiO5/CaCl2 composite cement. Fifty maxillary anterior teeth were
      instrumented according to step-back technique and filled with experimental and
      control materials. To evaluate the sealing ability, a fluid transport model using
      glucose was employed for quantitative analysis of endodontic microleakage. To
      evaluate antibacterial activity, E. colias (ATCC 25922) was cultivated on agar
      plates. Results showed that the sealing ability of Ca3SiO5/CaCl2 composite cement
      and cortisomol paste were higher than that of zinc oxide-eugenol (ZOE) cement,
      and that no significant difference was observed between Ca3SiO5/CaCl2 composite
      cement and cortisomol paste. On antibacterial activity, Ca3SiO5/CaCl2 composite
      cements composed of varying amounts of CaCl2 (0-15%) exhibited similar levels of
      activity against E. coliasas calcium hydroxide cement, whereas cortisomol paste
      had little effect on E. colias. All these results suggested that Ca3SiO5/CaCl2
      composite cement demonstrated good potential for root canal treatment
      applications.

PMID- 22864216
TI  - Effect of different amounts of 3-methacryloxypropyltrimethoxysilane on the
      flexural properties and wear resistance of alumina reinforced PMMA.
AB  - This study evaluated the different amounts of 3
      methacryloxypropyltrimethoxysilane (MPS) coated alumina filler particles on
      flexural strength and wear resistance of alumina reinforced polymethyl
      methacrylate (PMMA) denture base. Ten mass% of alumina filler silanized with 0,
      0.1, 0.2, or 0.4 mass% of MPS was blended with PMMA. PMMA without alumina
      particles served as control.Specimens were prepared for flexural strength and
      wear resistance tests (n=10). Flexural strength was determined using a 3-point
      bending test and volume loss was measured by in-vitro 2-body wear-testing. The
      results were analyzed by One-way ANOVA and Tamhane's test (alpha=0.05). Flexural
      strength ranged from 95.1-117.8 MPa, while volume loss ranged from 0.038-0.160
      mm3. Statistical analysis indicated the 0.1 mass% MPS silanized group had
      significantly higher flexural strength and lower volume loss than the control
      group. Adding alumina filler silanized with 0.1 mass% MPS resulted in an
      improvement of the flexural strength and wear resistance of PMMA.

PMID- 22864217
TI  - Production of a calcium silicate cement material from alginate impression
      material.
AB  - The purpose of this study was to synthesize biomaterials from daily dental waste.
      Since alginate impression material contains silica and calcium salts, we aimed to
      synthesize calcium silicate cement from alginate impression material. Gypsum
      based investment material was also investigated as control. X-ray diffraction
      analyses revealed that although firing the set gypsum-based and modified
      investment materials at 1,200 degrees C produced calcium silicates, firing the
      set alginate impression material did not. However, we succeeded when firing the
      set blend of pre-fired set alginate impression material and gypsum at 1,200
      degrees C. SEM observations of the powder revealed that the featured porous
      structures of diatomite as an alginate impression material component appeared
      useful for synthesizing calcium silicates. Experimentally fabricated calcium
      silicate powder was successfully mixed with phosphoric acid solution and set by
      depositing the brushite. Therefore, we conclude that the production of calcium
      silicate cement material is possible from waste alginate impression material.

PMID- 22864218
TI  - Preparation and characterization of a BisGMA-resin dental restorative composites
      with glass, silica and titania fillers.
AB  - A photo-polymerizable Bisphenol-A diglycidylether methacrylate resin was
      characterized by Fourier transform infrared spectroscopy after its irradiation
      under different conditions to identify the best curing. Bonding-agent free
      composites with particles of ball-milled glass, silica and titania at loading of
      10 and 50%wt were prepared, and their viscoelastic properties investigated by
      dynamic mechanical analysis, in experimental conditions close to the working
      environment in the mouth. All composites showed good stability at the considered
      conditions. The stiffest composite was the silica one, which was based on the
      smallest primary particles. The storage moduli close to room temperature (25
      degrees C) and mastication frequency (1 Hz) were extracted as reference bending
      moduli for the materials, and compared to static compressive moduli measured by
      nanoindentation performed by atomic force microscopy.Nanoindentation showed
      qualitative results in agreement with dynamic mechanical analysis as to the
      ranking of different materials, while resulting in approximately two-fold elastic
      modulus.

PMID- 22864219
TI  - An evaluation of dental operative simulation materials.
AB  - The study was to evaluate the performance of different materials used in dental
      operative simulation and compare them with those of natural teeth. Three typical
      phantom teeth materials were compared with extracted permanent teeth by a
      nanoindentation system and evaluated by students and registered dentists on the
      drilling sensation of the materials. Moreover, the tool life (machinability) of
      new cylindrical diamond burs on cutting the sample materials was tested and the
      burs were observed. Although student and dentist evaluations were scattered and
      inconclusive, it was found that elastic modulus (E) and hardness (H) were not the
      main factors in determining the drilling sensation of the materials. The
      sensation of drilling is a reflection of cutting force and power consumption.An
      ideal material for dental simulation should be able to generate similar drilling
      resistance to that of natural tooth, which is the machinability of the material.

PMID- 22864220
TI  - Predicting in vivo failure of rotary nickel-titanium endodontic instruments under
      cyclic fatigue.
AB  - The aim of this study was to examine the lifespan or number of cycles to failure
      of tapered rotary nickel-titanium (Ni-Ti) endodontic instruments. Simulated root
      canals with different curvatures were used to determine a relation between canal
      curvature and instrument lifespan. Using a novel mathematical model for the
      deformation of pseudoelastic Ni-Ti alloy, it was shown that maximum stress need
      not necessarily occur at the outer layer. On the basis of this observation, the
      Coffin-Manson relation was modified with parameters determined from this
      experiment. Results showed that the number of cycles to failure was influenced by
      the angle and radius of canal curvature and the size of instrument at the
      beginning of canal curvature. The resulting quantitative mathematical relation
      could be used to predict the lifespan of rotary Ni-Ti endodontic instruments
      under clinical conditions and thereby reduce the incidence of instrument failure
      in vivo.

PMID- 22864221
TI  - Effect of dual-peak LED unit on the polymerization of coinitiator-containing
      composite resins.
AB  - The purpose of the present study was to evaluate the effect of dual-peak LED on
      the polymerization of coinitiator-containing composite resins. For this,
      microhardness, degree of conversion (DC), and polymerization shrinkage were
      evaluated. Specimens (coinitiator-containing: Aelite LS Posterior, Tetric
      EvoCeram, and Vit-l-escence; only camphorquinone-containng: Filtek Z350 and
      Grandio) were light cured using a quartz-tungsten-halogen (QTH: OP), a single
      peak light-emitting diode (LED) (L. E. Demetron: DM), and a dual-peak LED (G
      light: GL), respectively. All specimens light cured using GL showed the highest
      microhardness both on the top and bottom surfaces compared with the values
      obtained using the rest light-curing units (LCUs). DC had no consistent trend
      correspond to the LCU, but rather product specific. OP yielded the lowest
      polymerization shrinkage on the specimens. The coinitiator-containing composite
      resins achieved the highest microhardness by the dual-peak LED (GL). However, the
      influence of GL on DC and polymerization shrinkage of the specimens was not
      consistent.

PMID- 22864222
TI  - A study for biofilm removing and antimicrobial effects by microbubbled tap water
      and other functional water, electrolyzed hypochlorite water and ozonated water.
AB  - The purpose of this study was to examine the biofilm removing and antimicrobial
      effects of microbubbled tap water and other functional water. The biofilm removal
      test showed that the activity of microbubbled tap water against the biofilm of
      Candida albicans and Streptococcus mutans was significantly higher than that of
      ordinary tap water (p<0.01). When the antimicrobial activities of two types of
      functional water were compared, the activity of electrolyzed hypochlorite water
      was significantly stronger than that of the ozonated water (p<0.01). The
      antimicrobial effect of the electrolyzed hypochlorite water was increased in the
      microbubbled form, and was stronger than microbubbled tap water. The same results
      were obtained not only for biofilms, but also for planktonic microbes. Our
      results demonstrated that the microbubbled water showed strong biofilm removing
      effects. Moreover, the application of functional water, such as electrolyzed
      hypochlorite microbubbled water was effective for both removing and sterilizing
      biofilms.

PMID- 22864223
TI  - Effect of mold temperature on the microstructure and corrosion properties of a 14
      karat gold alloy.
AB  - The objective of this research was to investigate the effect of mold temperature
      on grain interior and grain boundary reactions in a14-karat gold alloy. The alloy
      (Au-15%Ag-3%Pd-24 mass%Cu) was cast into an investment with different mold
      temperatures (22, 250,400, and 700 degrees C) and then analyzed using SEM, X-ray
      diffraction, and potentiodynamic polarization tests. Lower mold temperatures(22
      and 250 degrees C) retarded a grain boundary reaction evidently present when
      using higher mold temperatures (400 and 700 degrees C). Phase separation, which
      was manifested as a dual phase grain boundary nodular formation, was observed at
      a higher degree at 400 degrees C mold temperature than at 700 degrees C. The
      corrosion potentials of alloys cast at lower mold temperatures were more noble
      than those cast at higher mold temperatures, suggesting improved corrosion
      properties. Results of this study showed that the microstructure, crystalline
      phases present, and corrosion properties of 14-karat gold alloy were keenly
      influenced by the mold temperature, which controls and influences the cooling
      rate.

PMID- 22864224
TI  - Osteoblast compatibility of materials depends on serum protein absorbability in
      osteogenesis.
AB  - Titanium has an osseointegrative property, while hydroxyapatite has an
      osteoconductive property. It remains a matter of controversy among researchers
      whether hydroxyapatite has higher osteoblast compatibility than titanium. Here,
      we compared the activities between osteoblasts cultured on titanium and those
      cultured on hydroxyapatite. An osteoblast-like cell line, MC3T3-E1, was cultured
      on machined titanium, evaporated titanium, and hydroxyapatite disks to compare
      the affinity of osteoblasts to each of these materials. The adhesion and
      proliferation of MC3T3-E1 cells were higher on hydroxyapatite disks than on the
      other disks. Osteoblast differentiation was not affected by the nature of disks
      investigated, but calcium was more easily deposited on the hydroxyapatite disks.
      The amount of absorbed serum proteins detected on hydroxyapatite was greater than
      that on titanium. In conclusion, our results indicate hydroxyapatite is a more
      suitable material for osteoblast growth than titanium because of its higher
      absorption of serum proteins.

PMID- 22864226
TI  - Surface roughness and color change of a composite: influence of beverages and
      brushing.
AB  - This study evaluated the influence of beverages and brushing on the surface
      roughness(SR) and color change(?E) of a composite resin.For this, 120-disks(10
      mm*2 mm) of composite resin(Filtek-Z250) were prepared and polished. Initials
      SR(Ra-MUm) and color(CIELab-system) were measured with rugosimeter and
      spectrophotometer; specimens were divided into four groups(red wine, soft drink,
      sugar cane spirit, or artificial saliva=control) and three subgroups(without
      brushing; brushed with Colgate or with Close-Up). Specimens were immersed in the
      beverage 5*/day, for 5', over 30 day, being two subgroups brushed(120
      strokes/day). Color was measuredat 15th day, 30th day and after repolishment; SR
      at 30th day. ?E-values were statistically different after immersion in the
      beverages(p<0.05). Red wine promoted the highest alteration, followed by soft
      drink=sugar cane spirit and finally saliva. At 30th day, specimens exhibited ?E
      higher than 15th day; after repolishing, ?E was similar to 15th day. Beverages
      and brushing negatively influenced the SR. Therefore, ?E and SR can be influenced
      by beverages and brushing.

PMID- 22864225
TI  - Periodontal repair following implantation of beta-tricalcium phosphate with
      different pore structures in Class III furcation defects in dogs.
AB  - The aim of this study was to investigate the effect of the pore characteristics
      of beta-tricalcium phosphate (beta-TCP) on periodontal healing in class III
      furcation defects in dogs. Two types of beta-TCP were prepared for grafting; 1) a
      tunnel pipe structure with an inner diameter of 300 MUm, and 2) continuous pore
      structure with interconnected macropores. The furcations of thirty mandibular
      premolar teeth were implanted with each type of beta-TCP or were left untreated
      as control. The dogs were sacrificed 8 weeks post-surgery, and healing was
      evaluated histologically. Downgrowth of junctional epithelium in the tunnel
      structure group was significantly less than that in the other two groups
      (p<0.01). There was significantly more new bone formation and new cementum
      formation in the tunnel structure group than that in the other two groups
      (p<0.01). These findings suggested that beta-TCP with a tunnel pipe structure
      promotes periodontal healing in class III furcation defects.

PMID- 22864227
TI  - X-ray diffraction analysis of three-dimensional self-reinforcing monomer and its
      chemical interaction with tooth and hydroxyapatite.
AB  - According to the 'Adhesion-Decalcification' concept, specific functional monomers
      within dental adhesives can ionically interact with hydroxyapatite (HAp). Some
      specific functional monomers form monomer-Ca salts due to chemical interactions.
      The chemical stability of the monomer-Ca salts was thought to contribute to bond
      durability. In the present study, we analyzed the chemical interaction between an
      acidic three-dimensional self-reinforcing monomer (3D-SR) of Bond Force and
      enamel, dentin and HAp, and assessed its chemical stability by thin-fi lm X-ray
      diffraction (TF-XRD). 3D-SR forms a hydrolysis-resistant Ca-salt on the dentin in
      a clinical application time period and on enamel and HAp in a longer time period.
      This suggests that the functional monomer 3D-SR is able to contribute to bond
      durability.

PMID- 22864228
TI  - NSAID-associated lower gastrointestinal bleeding: where do we stand?

PMID- 22864229
TI  - Identification of genes differentially expressed in grapevine associated with
      resistance to Elsinoe ampelina through suppressive subtraction hybridization.
AB  - Anthracnose, caused by the biotrophic fungus Elsinoe ampelina, is an economically
      devastating disease of grapevine (Vitis vinifera L.) prevalent in warm and humid
      regions of the world. In order to investigate the molecular resistance mechanisms
      and identify genes related to anthracnose resistance in grapevine, a Suppression
      Subtractive Hybridization (SSH) library was constructed using mixed cDNAs
      prepared from leaves of Chinese wild Vitis quinquangularis clone 'Shang-24', cDNA
      prepared from leaves infected with the pathogen E. ampelina served as tester and
      cDNA from mock-inoculated leaves as driver. A total of 670 high-quality ESTs were
      clustered and assembled into a collection of 461 unique genes comprising 85
      contigs and 376 singletons. By Gene ontology (GO) analysis 310 unigenes were
      assigned to 22 GO slims within the molecular function category, while 317
      unigenes could be sorted into 43 GO slims within the biological process category.
      The expression profiles of 20 selected genes, monitored by quantitative RT-PCR,
      indicated that expression of these genes in the E. ampelina-resistant 'Shang-24'
      was quicker and more intense, than in the susceptible 'Red Globe' where the
      reaction was delayed and limited. The results imply that these up-regulated genes
      could be involved in grapevine responses against E. ampelina infection.

PMID- 22864230
TI  - Coronary computed tomography angiography-based coronary risk stratification in
      subjects presenting with no or atypical symptoms.
AB  - BACKGROUND:  Coronary computed tomography angiography (CTA) findings of positive
      vessel remodeling and low-attenuation plaque, referred to as computed tomography
      verified high-risk plaque (CT-HRP), have been reported to be associated with the
      development of subsequent acute coronary syndromes. The aim of this study was to
      examine the usefulness of coronary CTA for coronary risk re-stratification of
      patients with asymptomatic and atypical chest symptoms. METHODS AND RESULTS:  A
      total of 1,139 subjects (M/F 602/537; mean age, 61.5+/-9.3 years) who were either
      asymptomatic or presented with atypical chest symptoms underwent coronary 64- or
      320-slice multidetector computed tomography angiography and Agatston score. Age,
      sex, coronary risk factors, including hypertension, diabetes mellitus (DM),
      dyslipidemia, and smoking were investigated as predictors for CT-HRP on
      multivariate analysis using logistic regression analysis. CT-HRP was observed in
      72 patients (6.3%). Based on Framingham risk scores (FRS), CT-HRP was observed in
      0/94 subjects (0.0%) in the low-risk group, 35/806 (4.3%) in the intermediate
      risk group, and 37/239 (15.5%) in the high-risk group. On logistic regression
      analysis significant predictors for CT-HRP in intermediate- and high-risk
      subjects were male sex (odds ratio [OR] 2.829; 95% confidence interval [CI] 1.460
      5.479, P=0.0021), DM (OR 2.418; 95% CI 1.420-4.116, P=0.0011), and current
      smoking (OR 1.922; 95% CI 1.096-3.371, P=0.0160). CT-HRP prevalence for Agatston
      scores >500 and >250 was lower in the intermediate- and high-risk groups,
      respectively. CONCLUSIONS:  In asymptomatic subjects and those presenting with
      atypical chest pain who have a more than an intermediate risk, coronary CTA is
      contributory to FRS. Male sex, DM and smoking were independent predictors of
      vulnerable plaque in the more than intermediate-risk group. 

PMID- 22864231
TI  - Coronary flow reserve evaluated by quantitative perfusion magnetic resonance
      imaging in patients with nonalcoholic fatty liver disease.

PMID- 22864232
TI  - Detection of silver(I) ions based on the controlled self-assembly of a perylene
      fluorescence probe.
AB  - In the current work, we report a label-free fluorescence turn-on approach for the
      sensitive and selective sensing of Ag(+). A cationic perylene derivative,
      compound A, was used as the fluorescence probe. Compound A monomer is strongly
      fluorescent, and the fluorescence can be efficiently quenched through self
      aggregation (self-assembly). A cytosine (C)-rich oligonucleotide, oligo-C, was
      employed. In the absence of Ag(+), oligo-C induced strong compound A aggregation
      due to electrostatic interactions in aqueous media, and very weak fluorescence
      signal was detected. However, in the presence of Ag(+), the specific interactions
      between oligo-C and Ag(+) induced hairpin structure formation of oligo-C through
      C-Ag(+)-C bonding interactions. Oligo-C binding to compound A aggregates was
      weakened; therefore, compound A monomer could be released and detected. The
      intensity of the fluorescence signal was directly related to the amount of Ag(+)
      added to the assay solution. Our method is highly sensitive-a limit of detection
      of 5nM was obtained-and also very selective. Ag(+) detection in complex sample
      mixtures was also demonstrated.

PMID- 22864233
TI  - Microplate well coverage mixing using superhydrophobic contact.
AB  - Two important challenges in microplate instrumentation are to achieve full well
      sample coverage and complete mixing. An effective approach of using
      superhydrophobic rods to accomplish these challenges is reported here.
      Experiments conducted showed that analytes above 50MUl could be made to
      completely cover the bottom of 96-well standard and transparency microplates.
      Complete mixing was accomplished by moving the rod parallel to the well bottom
      while contacting the liquid. The approach is simple and controlled, and it
      minimizes the problems of spillage and cross-contamination. It works with
      analytes with varied volumes and of different viscosities present in each well of
      the microplate.

PMID- 22864234
TI  - On the beam direction search space in computerized non-coplanar beam angle
      optimization for IMRT-prostate SBRT.
AB  - In a recent paper, we have published a new algorithm, designated 'iCycle', for
      fully automated multi-criterial optimization of beam angles and intensity
      profiles. In this study, we have used this algorithm to investigate the
      relationship between plan quality and the extent of the beam direction search
      space, i.e. the set of candidate beam directions that may be selected for
      generating an optimal plan. For a group of ten prostate cancer patients, optimal
      IMRT plans were made for stereotactic body radiation therapy (SBRT), mimicking
      high dose rate brachytherapy dosimetry. Plans were generated for five different
      beam direction input sets: a coplanar (CP) set and four non-coplanar (NCP) sets.
      For CP treatments, the search space consisted of 72 orientations (5 degrees 
      separations). The NCP CyberKnife (CK) space contained all directions available in
      the robotic CK treatment unit. The fully non-coplanar (F-NCP) set facilitated the
      highest possible degree of freedom in selecting optimal directions. CK(+) and
      CK(++) were subsets of F-NCP to investigate some aspects of the CK space. For
      each input set, plans were generated with up to 30 selected beam directions.
      Generated plans were clinically acceptable, according to an assessment of our
      clinicians. Convergence in plan quality occurred only after around 20 included
      beams. For individual patients, variations in PTV dose delivery between the five
      generated plans were minimal, as aimed for (average spread in V(95): 0.4%). This
      allowed plan comparisons based on organ at risk (OAR) doses, with the rectum
      considered most important. Plans generated with the NCP search spaces had
      improved OAR sparing compared to the CP search space, especially for the rectum.
      OAR sparing was best with the F-NCP, with reductions in rectum D(Mean), V(40Gy),
      V(60Gy) and D(2%) compared to CP of 25%, 35%, 37% and 8%, respectively. Reduced
      rectum sparing with the CK search space compared to F-NCP could be largely
      compensated by expanding CK with beams with relatively large direction components
      along the superior-inferior axis (CK(++)). Addition of posterior beams (CK(++) ->
      F-NCP) did not lead to further improvements in OAR sparing. Plans with 25 beams
      clearly performed better than 11-beam plans. For CP plans, an increase from 11 to
      25 involved beams resulted in reductions in rectum D(Mean), V(40Gy), V(60Gy) and
      D(2%) of 39%, 57%, 64% and 13%, respectively.

PMID- 22864235
TI  - Construction of alpha-amido-indanones via formal allenamide hydroacylation
      Nazarov cyclization.
AB  - A two-step modular synthesis of an alpha-hydroxycyclopentenone and alpha-amido
      indanones has been developed based on the Nazarov cyclization of 2-amido-1,4
      pentadien-3-ones, readily accessed via formal hydroacylation of allenamides.

PMID- 22864236
TI  - Distinct phenotypes in mixed connective tissue disease: subgroups and survival.
AB  - The aim of the present study was to assess the autoantibody profile, dominant
      clinical symptoms and cluster characteristics of different mixed connective
      tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were
      followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon,
      pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD),
      erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial
      cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and
      IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of
      patients was 52.9 +/- 12.4 years and the mean follow-up of the disease was 12.5
      +/- 7.2 years. Patients were classified into three cluster groups. Cluster 1 with
      77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In
      cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%;
      p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater
      than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001),
      myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was
      significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP
      antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP
      antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina,
      venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2,
      musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were
      most frequent in cluster 3. Cumulative survival assessment indicated cluster 1
      patients having the worst prognosis. Cluster analysis is valuable to
      differentiate among various subsets of MCTD and useful prognostic factor
      regarding the disease course.

PMID- 22864237
TI  - Extraction of betulin, trimyristin, eugenol and carnosic acid using water-organic
      solvent mixtures.
AB  - A solvent system consisting of ethyl acetate, ethyl alcohol and water, in the
      volume ratio of 4.5:4.5:1, was developed and used to extract, at room
      temperature, betulin from white birch bark and antioxidants from spices
      (rosemary, thyme, sage, and oregano) and white oak chips. In addition, under
      reflux conditions, trimyristin was extracted from nutmeg using the same solvent
      system, and eugenol from olives was extracted using a mixture of salt water and
      ethyl acetate. The protocol demonstrates the use of water in organic solvents to
      extract natural products from plants. Measurement of the free-radical scavenging
      activity using by 2,2-diphenyl-1-picrylhydrazyl (DPPH) indicated that the
      extraction of plant material using ethyl acetate, ethyl alcohol and water
      (4.5:4.5:1, v/v/v) was exhaustive when carried out at room temperature for 96 h.

PMID- 22864239
TI  - Cytoprotective effect of benzyl N'-(5-chloro-indol-3-yl-methylidene)
      hydrazinecarbodithioate against ethanol-induced gastric mucosal injury in rats.
AB  - Indolic compounds have attracted a lot of attention due to their interesting
      biological properties. The present study was performed to evaluate the subacute
      toxicity and anti-ulcer activity of BClHC against ethanol-induced gastric ulcers.
      Experimental animal groups were orally pre-treated with different doses of BClHC
      (50, 100, 200 and 400 mg/kg) in 10% Tween 20 solution (vehicle). Blank and ulcer
      control groups were pre-treated with vehicle. The positive group was orally
      pretreated with 20 mg/kg omeprazole. After one hour, all groups received absolute
      ethanol (5 mL/kg) to generate gastric mucosal injury except the blank control
      group which was administered the vehicle solution. After an additional hour, all
      rats were sacrificed, and the ulcer areas of the gastric walls determined.
      Grossly, the ulcer control group exhibited severe mucosal injury, whereas pre
      treatment with either derivative or omeprazole resulted in significant protection
      of gastric mucosal injury. Flattening of gastric mucosal folds was also observed
      in rats pretreated with BClHC. Histological studies of the gastric wall of ulcer
      control group revealed severe damage of gastric mucosa, along with edema and
      leucocytes infiltration of the submucosal layer compared to rats pre-treated with
      either BClHC or omeprazole where there were marked gastric protection along with
      reduction or absence of edema and leucocytes infiltration of the submucosal
      layer. Subacute toxicity study with a higher dose of derivative (5 g/kg) did not
      manifest any toxicological signs in rats. In conclusions, the present finding
      suggests that benzyl N'-(5-chloroindol-3-ylmethylidene)hydrazinecarbodithioate
      promotes ulcer protection as ascertained by the comparative decreases in ulcer
      areas, reduction of edema and leucocytes infiltration of the submucosal layer.

PMID- 22864238
TI  - Insights on cytochrome p450 enzymes and inhibitors obtained through QSAR studies.
AB  - The cytochrome P450 (CYP) superfamily of heme enzymes play an important role in
      the metabolism of a large number of endogenous and exogenous compounds, including
      most of the drugs currently on the market. Inhibitors of CYP enzymes have
      important roles in the treatment of several disease conditions such as numerous
      cancers and fungal infections in addition to their critical role in drug-drug
      interactions. Structure activity relationships (SAR), and three-dimensional
      quantitative structure activity relationships (3D-QSAR) represent important tools
      in understanding the interactions of the inhibitors with the active sites of the
      CYP enzymes. A comprehensive account of the QSAR studies on the major human CYPs
      1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and a few other CYPs are
      detailed in this review which will provide us with an insight into the
      individual/common characteristics of the active sites of these enzymes and the
      enzyme-inhibitor interactions.

PMID- 22864240
TI  - Synthesis and characterization of new thiazolidinones containing coumarin
      moieties and their antibacterial and antioxidant activities.
AB  - New coumarin derivatives, namely (2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo
      2-phenylthiazolidin-3-yl)acetamide, N-(2-(3-methoxyphenyl)-4-oxothiazolidin-3-yl)
      2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide, 2-(4-methyl-2-oxo-2H-chromen-7
      yloxy)-N-(4-oxo-2-(2,3,4trimethoxyphenyl)thiazolidin-3-yl)acetamide and N-(2-(4
      bromophenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7
      yloxy)acetamide) were synthesized starting from 4-methyl-7-hydroxycoumarin. The
      structures of the obtained compounds were confirmed by analytical IR and NMR
      spectra to elucidate the different positions of protons and carbons and as well
      as theoretical studies (DFT/B3LYP). The new compounds were screened for
      antibacterial activity. Most of them are more active against E. coli S. aureus
      and B. subtilis than standard references.

PMID- 22864241
TI  - A convenient ultrasound-promoted synthesis of some new thiazole derivatives
      bearing a coumarin nucleus and their cytotoxic activity.
AB  - Successful implementation of ultrasound irradiation for the rapid synthesis of a
      novel series of 3-[1-(4-substituted-5-(aryldiazenyl)thiazol-2-yl)hydrazono)ethyl]
      2H-chromen-2-ones 5a-h, via reactions of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)
      thiosemicarbazide (2) and the hydrazonoyl halides 3(4), was demonstrated. Also, a
      new series of 5-arylidene-2-(2-(1-(2-oxo-2H-chromen-3
      yl)ethylidene)hydrazinyl)thiazol-4(5H)-ones 10a-d were synthesized from reaction
      of 2 with chloroacetic acid and different aldehydes. Moreover, reaction of 2
      cyano-N'-(1-(2-oxo-2H-chromen-3-yl)ethylidene)-acetohydrazide (12) with
      substituted benzaldehydes gave the respective arylidene derivatives 13a-c under
      the conditions employed. The structures of the synthesized compounds were
      assigned based on elemental analyses and spectral data. Also, the cytototoxic
      activities of the thiazole derivative 5a was evaluated against HaCaT cells (human
      keratinocytes). It was found that compound 5a possess potent cytotoxic activity.

PMID- 22864242
TI  - Induction of apoptosis by ethanolic extract of Corchorus olitorius leaf in human
      hepatocellular carcinoma (HepG2) cells via a mitochondria-dependent pathway.
AB  - Corchorus olitorius L.,is a culinary and medicinal herb, widely used as a
      vegetable in several countries in Asia. Many studies have shown that C. olitorius
      contains several antioxidants and exhibits anti-inflammatory and anti
      proliferative activities in various in vitro and in vivo settings. Recently, C.
      olitorius has been approved for its antitumor activity; however, the underlying
      molecular mechanisms remain unclear. The goal of this study was to investigate
      the effects of ethanol extract of C. olitorius (ECO) on the growth of human
      hepatocellular carcinoma (HepG2) cells and gain some insights into the underlying
      mechanisms of its action. We found that HepG2 cells, treated with ECO for 24 h at
      a concentration higher than 12.5 MUg/mL, displayed a strong reduction in cell
      viability, whereas normal FL83B hepatocytes were not affected. DNA fragmentation
      and nuclear condensation were evidenced by the increased subG1 population of ECO
      treated HepG2 cells. ECO triggered the activation of procaspases-3 and -9 and
      caused the cleavage of downstream substrate, poly ADP-ribose polymerase (PARP),
      followed by down-regulation of the inhibitor of caspase-activated DNase (ICAD)
      signaling. Moreover, the increased release of cytochrome c from mitochondria with
      decreased membrane potential demonstrated the apoptosis induced through the
      caspases cascade. Our findings indicated that ECO might be effective against
      hepatocellular carcinoma through induction of apoptosis via mitochondria
      dependent pathway.

PMID- 22864243
TI  - Phenolic compounds and antioxidant activity of bulb extracts of six Lilium
      species native to China.
AB  - Lily (Lilium) is used as an important edible and medical plant species with a
      vague taxonomic classification and a long history in China. Bulbs of six Lilium
      species (L. regale, L. concolor, L. pumilum, L. leucanthum, L. davidii var.
      unicolor and L. lancifolium) native to China were investigated with a view to
      their exploitation as a potential source of natural antioxidants due to their
      phenolic composition and dietary antioxidant potential. The results showed that
      all bulb extracts exhibited strong antioxidant activities, which generally
      correlated positively with the total phenolic contents (r = 0.68 to 0.94), total
      flavonoid contents (r = 0.51 to 0.89) and total flavanol contents (r = 0.54 to
      0.95). High-performance liquid chromatography (HPLC) analysis revealed that rutin
      and kaempferol were the major phenolic components in the extracts. Hierarchical
      cluster analysis showed that L. regale belonged to the group with high phenolic
      content and strong antioxidant power. L. concolor and L. pumilum were arranged in
      one group characterized by moderate phenolic content and antioxidant capacity,
      while L. leucanthum, L. davidii var. unicolor and L. lancifolium were clustered
      in the third group with low phenolic content and weak antioxidant activity. These
      strongly suggest that lily bulbs may serve as a potential source of natural
      antioxidant for food and pharmaceutical applications.

PMID- 22864244
TI  - Spectroscopy and speciation studies on the interactions of aluminum (III) with
      ciprofloxacin and beta-nicotinamide adenine dinucleotide phosphate in aqueous
      solutions.
AB  - In this study, both experimental and theoretical approaches, including absorption
      spectra, fluorescence emission spectra, 1H- and 31P-NMR, electrospray ionization
      mass spectrometry (ESI-MS), pH-potentiometry and theoretical approaches using the
      BEST & SPE computer programs were applied to study the competitive complexation
      between ciprofloxacin (CIP) and b-nicotinamide adenine dinucleotide phosphate
      (NADP) with aluminum (III) in aqueous solutions. Rank annihilation factor
      analysis (RAFA) was used to analyze the absorption and fluorescence emission
      spectra of the ligands, the binary complexes and the ternary complexes. It is
      found, at the mM total concentration level and pH = 7.0, the bidentate
      mononuclear species [Al(CIP)]2+ and [Al(NADP)] predominate in the aqueous
      solutions of the Al(III)-CIP and Al(III)-NADP systems, and the two complexes have
      similar conditional stability constants. However, the pH-potentiometry results
      show at the mM total concentration level and pH = 7.0, the ternary species
      [Al(CIP)(HNADP)] predominates in the ternary complex system. Comparing predicted
      NMR spectra with the experimental NMR results, it can be concluded that for the
      ternary complex, CIP binds to aluminum ion between the 3-carboxylic and 4
      carbonyl groups, while the binding site of oxidized coenzyme II is through the
      oxygen of phosphate, which is linked to adenosine ribose, instead of
      pyrophosphate. The results also suggested CIP has the potential to be a probe
      molecular for the detection of NADP and the Al(III)-NADP complexes under
      physiological condition.

PMID- 22864245
TI  - Improvement in the water retention characteristics of sandy loam soil using a
      newly synthesized poly(acrylamide-co-acrylic acid)/AlZnFe2O4 superabsorbent
      hydrogel nanocomposite material.
AB  - The use of some novel and efficient crop nutrient-based superabsorbent hydrogel
      nanocomposites (SHNCs), is currently becoming increasingly important to improve
      the crop yield and productivity, due to their water retention properties. In the
      present study a poly(Acrylamide-co-acrylic acid)/AlZnFe2O4 superabsorbent
      hydrogel nanocomposite was synthesized and its physical properties characterized
      using Energy Dispersive X-ray (EDX), FE-SEM and FTIR spectroscopic techniques.
      The effects of different levels of SHNC were studied to evaluate the moisture
      retention properties of sandy loam soil (sand 59%, silt 21%, clay 19%, pH 7.4, EC
      1.92 dS/m). The soil amendment with 0.1, 0.2, 0.3 and 0.4 w/w% of SHNC enhanced
      the moisture retention significantly at field capacity compared to the untreated
      soil. Besides, in a separate experiment, seed germination and seedling growth of
      wheat was found to be notably improved with the application of SHNC. A delay in
      wilting of seedlings by 5-8 days was observed for SHNC-amended soil, thereby
      improving wheat plant growth and establishment.

PMID- 22864246
TI  - The inhibitory effects of vinylphosphonate-linked thymidine dimers on the
      unidirectional translocation of PcrA helicase along DNA: a molecular modelling
      study.
AB  - The PcrA DNA helicases are important bacterial enzymes and quintessential
      examples of molecular motors. Through conformational changes caused by ATP
      hydrolysis, they move along the template double helix, breaking the hydrogen
      bonds holding the two strands together, and separating the template chains so
      that the genetic information can be accessed. The flexibility of the DNA backbone
      is essential for the unidirectional translocation of PcrA. A modified DNA
      substrate with reduced backbone rotational flexibility (via an incorporated
      vinylphosphonate linkage) has previously been designed and tested as a helicase
      substrate. The results show that a single modification on the backbone is
      sufficient to inhibit the activity of PcrA. In this paper a range of molecular
      simulation methods have been applied to examine the structural origins of this
      inhibitory effect, as it tests our theories of the mechanism of action of this
      motor. We observe that the chemical modification has different effects on the
      energetics of DNA translocation through the protein as it reaches different sub
      sites.

PMID- 22864247
TI  - Psychological and culturally-influenced risk factors for the incidence and
      persistence of low back pain and associated disability in Spanish workers:
      findings from the CUPID study.
AB  - OBJECTIVE: To assess the importance of psychological and culturally-influenced
      factors as predictors of low back pain (LBP) incidence and persistence in Spanish
      workers. METHODS: As part of the international Cultural and Psychosocial
      Influences in Disability (CUPID) study, 1105 Spanish nurses and office workers
      answered questions at baseline about LBP in the past month and past year,
      associated disability, occupational lifting, smoking habits, health beliefs,
      mental health, and distress from common somatic symptoms. At 12-month follow-up,
      they were asked about LBP and associated disability in the past month.
      Associations with LBP incidence and persistence were assessed by log binomial
      regression, and characterised by prevalence rate ratios (PRRs) with associated
      95% CIs. RESULTS: 971 participants (87.9%) completed follow-up. Among 579 with no
      LBP at baseline, 22.8% reported LBP at follow-up. After adjustment for sex, age
      and occupation, new LBP was predicted by poor mental health (PRR 1.5, 95% CI 1.0
      to 2.2), somatising tendency (PRR 1.8, 95% CI 1.2 to 2.7) and presence of LBP for
      >1 month in the year before baseline (PRR 4.7, 95% CI 3.1 to 6.9). Among 392
      subjects who had LBP at baseline, 59.4% reported persistence at follow-up, which
      was associated with presence of symptoms for >1 month in the 12 months before
      baseline (PRR 1.4, 95% CI 1.2 to 1.7) and more weakly with somatising tendency,
      and with adverse beliefs about LBP work-relatedness and prognosis. CONCLUSIONS:
      In Spain, as in northern European countries, psychological and culturally
      influenced factors have an important role in LBP development and persistence.

PMID- 22864248
TI  - Worksite mental health interventions: a systematic review of economic
      evaluations.
AB  - OBJECTIVE: To give an overview of the evidence on the cost-effectiveness (CE) and
      financial return of worksite mental health interventions. METHODS: A systematic
      search was conducted in relevant databases. Included economic evaluations were
      classified into two groups based on type of intervention: (1) aimed at prevention
      or treatment of mental health problems among workers or (2) aimed at return to
      work (RTW) for workers sick-listed from mental health problems. The quality of
      the included economic evaluations was assessed using the Consensus Health
      Economic Criteria list (CHEC-list). RESULTS: Ten economic evaluations were
      included in this systematic review. All four economic evaluations on the
      prevention or treatment of mental health problems found a positive cost-benefit
      ratio, although three of these studies had low to moderate methodological
      quality. In five out of six economic evaluation studies on RTW interventions, no
      favourable CE or cost-benefit balance was found. One study of moderate
      methodological quality reported on a positive CE balance. CONCLUSIONS: Due to a
      limited number of economic evaluations on worksite mental health interventions of
      which a majority was lacking methodological quality or lacking evidence, only a
      tentative conclusion can be drawn from the results of this systematic review.
      Worksite interventions to prevent or treat mental health problems might be cost
      effective, while those RTW interventions that included a full economic evaluation
      aimed at depressed employees do not seem to be cost-beneficial. More high-quality
      economic evaluation studies of effective worksite mental health interventions are
      needed to get more insight into the economic impact of worksite mental health
      interventions.

PMID- 22864249
TI  - Occupational exposure to chlorinated solvents and risks of glioma and meningioma
      in adults.
AB  - OBJECTIVES: Chlorinated solvents are classified as probable or possible
      carcinogens. It is unknown whether exposure to these agents increases the risk of
      malignant or benign brain tumours. Our objective was to evaluate associations of
      brain tumour risk with occupational exposure to six chlorinated solvents (i.e.,
      dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane,
      trichloroethylene and perchloroethylene). METHODS: 489 glioma cases, 197
      meningioma cases and 799 controls were enrolled in a hospital-based case-control
      study conducted at three U.S.A. hospitals in Arizona, Massachusetts and
      Pennsylvania. Information about occupational history was obtained through a
      detailed inperson interview that included job-specific modules of questions such
      that the interview was tailored to each individual's particular work history. An
      industrial hygienist assessed potential solvent exposure based on this
      information and an exhaustive review of the relevant industrial hygiene
      literature. Unconditional logistic regression models were used to calculate OR
      and 95% CI for each solvent for ever/never, duration, cumulative, average weekly
      and highest exposure. RESULTS: Overall, we found no consistent evidence of an
      increased risk of glioma or meningioma related to occupational exposure to the
      six chlorinated solvents evaluated. There was some suggestion of an association
      between carbon tetrachloride and glioma in analyses restricted to exposed
      subjects, with average weekly exposure above the median associated with increased
      risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2).
      CONCLUSIONS: We found no consistent evidence for increased brain tumour risk
      related to chlorinated solvents.

PMID- 22864250
TI  - Higher blood lead levels in rural than urban pregnant women in eastern Nigeria.

PMID- 22864251
TI  - Evaluation of a nationally funded state-based programme to reduce fatal
      occupational injuries.
AB  - BACKGROUND: The Fatality Assessment and Control Evaluation (FACE) programme was
      established by the National Institute for Occupational Safety and Health to help
      prevent occupational traumatic fatalities by funding states to conduct targeted
      fatality investigations within cause-specific focus areas and associated
      prevention efforts. PURPOSE: To investigate the impact of the state-based FACE
      programme on two previous focus areas. METHODS: A longitudinal time-series
      analysis spanning 22 years compared state fatality rates for occupational falls
      and electrocutions before and after FACE programme funding with states not
      receiving FACE programme funding. Lag periods were utilised to allow time for the
      programme to have an effect, and rates were adjusted for a variety of covariates.
      Separate analyses were conducted for each injury outcome. RESULTS: A reduction in
      fall fatality rates that was of borderline significance (1-year lag adjRR=0.92
      (0.84 to 1.00)) and a non-significant reduction in electrocution fatality rates
      (3-year lag adjRR=0.92 (0.82 to 1.03)) were observed in states with FACE
      programme funding, Best-fit models presented two separate lag periods.
      CONCLUSIONS: While it is challenging to quantitatively evaluate effectiveness of
      programmes such as FACE, the data suggest the FACE programme may be effective in
      preventing occupational injury deaths within its outcome focus areas throughout
      the state. It is important to look for ways to measure intermediate effects more
      precisely, as well as ways to maintain effects over time.

PMID- 22864252
TI  - Risk factors for new onset and persistence of multi-site musculoskeletal pain in
      a longitudinal study of workers in Crete.
AB  - OBJECTIVES: To explore occupational and psychological risk factors for the
      incidence and persistence of multi-site musculoskeletal pain. METHODS: We
      conducted a longitudinal investigation of three occupational groups in Crete,
      Greece. Baseline information was obtained at interview about pain in the past
      year at each of six anatomical sites, and about possible risk factors for
      subsequent symptoms. Twelve months later, subjects were re-interviewed about pain
      at the same anatomical sites in the past month. Pain at two or more sites was
      classed as multi-site. Associations with new development and persistence of multi
      site pain at follow-up were assessed by logistic regression. RESULTS: Analysis
      was based on 518 subjects (87% of those originally selected for study). At follow
      up, multi-site pain persisted in 217 (62%) of those who had experienced it in the
      year before baseline, and was newly developed in 27 (17%) of those who had not.
      Persistence of multi-site pain was significantly related to physical loading at
      work, somatising tendency and beliefs about work as a cause of musculoskeletal
      pain, with OR (95% CI) for the highest relative to the lowest exposure categories
      of 2.3 (1.0 to 5.6), 2.6 (1.5 to 4.6) and 1.9 (1.1 to 3.3) respectively.
      Development of new multi-site pain was most strongly associated with working for
      >=40 h per week (OR 5.0, 95% CI 1.1 to 24.0). CONCLUSIONS: Our findings confirm
      the importance of both physical loading at work and somatising tendency as risk
      factors for multi-site pain, and suggest that persistence of pain is also
      influenced by adverse beliefs about work causation.

PMID- 22864253
TI  - A sorting strategy for C. elegans based on size-dependent motility and
      electrotaxis in a micro-structured channel.
AB  - Caenorhabditis elegans (C. elegans) is a model organism widely utilized in
      various fundamental studies in developmental, neural and behavioural biology. The
      worm features four distinct larval stages, and many research questions are stage
      specific; therefore, it is necessary to sort worms by their developmental stages,
      which are typically represented by different size ranges. However, manually
      synchronizing large populations of worms is time-consuming and labour-intensive,
      and the commercially available automated sorter is massive and expensive.
      Realizing the need for a cost-effective and simple micro-platform for sorting, we
      report an inexpensive and novel method to accomplish this goal. The proposed
      micro-platform features hexagonally arrayed microstructures with geometric
      dimensions optimized for the maximum motility of the worms based on their sizes.
      In each of the optimized micro-structured platforms, only the worms with the
      targeted size swim continuously with the maximum undulation frequency.
      Additionally, the persistent and directed movement of the worms can be achieved
      by applying an electric field along the channel. Based on the optimally spaced
      microstructures and the electrotaxis behaviour of the worms, we demonstrate the
      feasibility of a sorting strategy of C. elegans based on their size-dependent
      swimming behaviour. This micro-platform can also be used for other applications,
      such as behavioural studies of normal and locomotion-defective mutant worms in
      complex structures.

PMID- 22864254
TI  - A porcine model of familial adenomatous polyposis.
AB  - We created gene-targeted pigs with mutations in the adenomatous polyposis coli
      (APC) gene (APC) that are orthologous to those responsible for human familial
      adenomatous polyposis (FAP). One-year-old pigs with the APC(1311) mutation
      (orthologous to human APC(1309)) have aberrant crypt foci and low- and high-grade
      dysplastic adenomas in the large intestine, similar to the precancerous lesions
      that develop in patients with FAP. Dysplastic adenomas accumulate beta-catenin
      and lose heterozygosity of APC. This large-animal, genetic model of FAP will be
      useful in the development of diagnostics and therapeutics for colorectal cancer.
      DNA sequence data: NCBI accession number GU951771.

PMID- 22864256
TI  - Electrocatalytic reduction of coreactant by highly loaded dendrimer-encapsulated
      palladium nanoparticles for sensitive electrochemiluminescent immunoassay.
AB  - Dendrimer-encapsulated palladium nanoparticles anchored on a carbon nanohorn were
      designed as a nonenzymatic tracing tag for sensitive quantum dot-based
      electrochemiluminescent immunoassay by electrocatalytic reduction of dissolved
      O(2) as the coreactant.

PMID- 22864257
TI  - Increased autonomic activation in vicarious embarrassment.
AB  - We studied the somatovisceral response pattern of vicarious embarrassment for
      someone else's inappropriate condition. Participants (N=54) were confronted with
      hand-drawn sketches depicting public situations and were instructed to rate the
      intensity of their vicarious embarrassment. The inappropriate condition varied
      according to the attribution of intentionality (absent/present) and awareness
      (absent/present). Irrespective of these attributions, participants reported
      stronger vicarious embarrassment in comparison to neutral situations. Across a
      set of eleven somatovisceral variables vicarious embarrassment elicited a pattern
      of increased autonomic activation which was modulated by the awareness of the
      protagonist about the ongoing norm violation. The somatovisceral response pattern
      matches previous findings for the first-person experience of embarrassment.
      Together, these results support the hypothesis that processes of perspective
      taking also mediate the vicarious experience of embarrassment.

PMID- 22864255
TI  - Effects of scleroderma antibodies and pooled human immunoglobulin on anal
      sphincter and colonic smooth muscle function.
AB  - BACKGROUND & AIMS: Patients with systemic sclerosis (SSc) have impairments in
      gastrointestinal smooth muscle function. The disorder has been associated with
      circulating antibodies to cholinergic muscarinic the type-3 receptor (M(3)-R). We
      investigated whether it is possible to neutralize these antibodies with pooled
      human IgGs (pooledhIgG). METHODS: We studied the effects of IgGs purified from
      patients with SSc (SScIgGs) on cholinergic nerve stimulation in rat colon
      tissues. We also examined the effects of SScIgGs on M(3)-R activation by
      bethanechol (BeCh), M(3)-R occupancy, and receptor binding using
      immunofluorescence, immunoblot, and enzyme-linked immunosorbent analyses of human
      internal anal sphincter (IAS) smooth muscle cells, before and after
      administration of pooledhIgG. Functional displacement of M(3)-R occupancy by the
      SScIgGs was compared with that of other IgGs during the sustained phase of BeCh
      induced contraction of intact smooth muscles from rats. RESULTS: SScIgG
      significantly attenuated neurally mediated contraction and acetylcholine release
      in rat colon as well as BeCh-induced sustained contraction of the IAS smooth
      muscle. In immunofluorescence analysis, SScIgG co-localized with M(3)-R. In
      immunoblot and enzyme-linked immunosorbent analyses, M(3)-R loop-2 peptide and
      human IAS SMC membrane lysates bound significant amounts of SScIgG, compared with
      IgGs from healthy individuals and pooledhIgG. Binding was attenuated
      significantly by application of pooledhIgG, which by itself had no significant
      effect. Incubation of samples with pooledhIgG, or mixing pooledhIgG with SScIgG
      before administration to tissues, significantly reduced binding of SScIgG,
      indicating that pooledhIgG prevents SScIgG blockade of M(3)-R. CONCLUSIONS: In
      studies of rat and human tissues, pooled human IgG prevent and reverses the
      cholinergic dysfunction associated with the progressive gastrointestinal
      manifestations of SSc by neutralizing functional M(3)-R antibodies present in the
      circulation of patients with SSc.

PMID- 22864258
TI  - Individual alpha neurofeedback training effect on short term memory.
AB  - Memory performance has been reported to be associated with electroencephalogram
      (EEG) alpha activity. This study aimed to improve short term memory performance
      by individual alpha neurofeedback training (NFT). With appropriate protocol
      designed for NFT, the experimental results showed that the participants were able
      to learn to increase the relative amplitude in individual alpha band during NFT
      and short term memory performance was significantly enhanced by 20 sessions of
      NFT. More importantly, further analysis revealed that the improvement of short
      term memory was positively correlated with the increase of the relative amplitude
      in the individual upper alpha band during training. In addition, effective
      strategies for individual alpha training varied among individuals and the most
      successful mental strategies were related to positive thinking.

PMID- 22864259
TI  - Ursodeoxycholic acid for nonalcoholic steatohepatitis.
AB  - The aim of this study was to evaluate the effects of ursodeoxycholic acid on
      patients with nonalcoholic steatohepatitis using meta-analysis. PubMed, EMBASE,
      Web of Science, Cochrane Library, Chinese Biomedical Databases, and article
      references were searched. We included randomized controlled trials using liver
      biopsy as a reference standard. We identified three eligible studies. Among
      histological responses, only lobular inflammation improved in the high-dose
      ursodeoxycholic acid subgroup compared with the control group [mean deviation
      (MD): -0.23 (-0.40, -0.06), P=0.008]. However, fibrosis may tend to increase [MD:
      0.08 (-0.04, 0.20), P=0.17]. Among biochemical responses, gamma-glutamyl
      transpeptidase reduction was significantly greater in the ursodeoxycholic acid
      group than in the placebo group, and the reduction tendency was only shown in the
      high-dose subgroup [MD: -35.58 (-52.60, -18.56), P<0.0001]. Serum total bilirubin
      increased in the high-dose ursodeoxycholic acid subgroup compared with the
      control group [MD: 0.43 (0.14, 0.72), P=0.004]. Ursodeoxycholic acid-treated
      patients did not differ significantly from control patients with regard to
      alanine transaminase, aspartate aminotransferase, and alkaline phosphatase
      activities. Adverse events were nonspecific and considered of no major clinical
      relevance. Ursodeoxycholic acid in monotherapy has no substantial positive effect
      on nonalcoholic steatohepatitis.

PMID- 22864260
TI  - Serological prevalence of hepatitis B virus and hepatitis C virus infection in
      the elderly population: Polish nationwide survey--PolSenior.
AB  - BACKGROUND: The hepatitis B virus (HBV) and hepatitis C virus (HCV) infections
      may seriously affect survival rate. The median length of life in developed
      countries is increasing and the elderly may be considered as an epidemiologically
      distinct group due to higher whole-life risk of blood-borne viral infections.
      AIM: To determine the seroprevalence of HBV and HCV infections in elderly
      individuals participating in a Polish nationwide survey - PolSenior. METHODS: A
      total of 4979 individuals aged 65 years and older were asked about past or
      present viral hepatitis, and a blood test was carried out for HBsAg and anti-HCV
      antibodies in 3826 individuals. The respondents were divided into six age groups
      of equal size: 65-69, 70-74, 75-79, 80-84, 85-89, and 90+ years. RESULTS: Past or
      present diagnosis of viral hepatitis was reported by 176 individuals (3.58%) and
      its prevalence was significantly most common in urban than in rural residents
      (4.02 vs. 2.92%; P=0.04). In multivariate analysis, only the job category was a
      significant variable (P=0.01) for the occurrence of viral hepatitis [most
      frequently in white-collar workers (3.56%) and least frequently in agricultural
      workers (1.47%)]. The overall prevalence of a positive HBsAg test was 1.12%
      (n=43) and that of an anti-HCV test was 2.93% (n=112). Only 12 anti-HCV-positive
      patients (10.7%) were aware of infection. Multivariate analyses did not indicate
      significant effects of age, sex, alcohol consumption, nutrition, marital or
      economic status, educational level, and site of residence on the incidence of HBV
      and HCV infections. HBsAg was associated with higher serum levels of aspartate
      aminotransferase, and anti-HCV with higher levels of aspartate aminotransferase
      and alanine aminotransferase. CONCLUSIONS: In elderly individuals, the
      seroprevalence of HBsAg is lower and the seroprevalence of anti-HCV is
      considerably higher than that in the general Polish population. The former may
      have been because of increased mortality from HBV-related complications and the
      latter of increased whole-life risk of infection. Programs for screening of
      elderly individuals for occult HCV infection should be considered.

PMID- 22864261
TI  - Total synthesis of ascididemin via anionic cascade ring closure.
AB  - A new and convergent synthesis of ascididemin is presented. Using an anionic
      cascade ring closure as the key step, this natural product is obtained in 45%
      overall yield in just 6 steps starting from 2'-fluoroacetophenone. This new
      approach was extended to the synthesis of a new isomer of ascididemin.

PMID- 22864262
TI  - High-throughput bacterial genome sequencing: an embarrassment of choice, a world
      of opportunity.
AB  - Here, we take a snapshot of the high-throughput sequencing platforms, together
      with the relevant analytical tools, that are available to microbiologists in
      2012, and evaluate the strengths and weaknesses of these platforms in obtaining
      bacterial genome sequences. We also scan the horizon of future possibilities,
      speculating on how the availability of sequencing that is 'too cheap to metre'
      might change the face of microbiology forever.

PMID- 22864263
TI  - Antimicrobials: Arming symbionts with antimalarials.

PMID- 22864265
TI  - Heterogeneous response of J-wave syndromes to beta-adrenergic stimulation.
AB  - BACKGROUND: Inferolateral early repolarization (ER) and Brugada syndrome manifest
      with J waves. Isoproterenol suppresses recurrent ventricular arrhythmias while
      reducing J waves in both disorders. OBJECTIVE: To characterize the effect of
      isoproterenol on J waves. METHODS: We analyzed the impact of isoproterenol on J
      waves in 20 patients with Brugada-type electrocardiogram (Br group) and 38
      patients with ER (ER group). RESULTS: In the ER group, J waves were present in
      inferior leads in 32 patients (84%) and in lateral leads in 23 patients (61%).
      Isoproterenol increased the heart rate by 75 beats/min in the ER group and by 71
      beats/min in the Br group (P = .20). The incidences of persistent (<= 0.05-mV
      decrease), decreased, and normalized J waves (residual J wave <= 0.05 mV) were
      20%, 80%, and 0% for Br group patients and 29%, 8%, and 63% for ER group
      patients, respectively (P <.001). Within the ER group, inferior J waves persisted
      in 34% of the cases, decreased in 9%, and normalized in 56% whereas lateral J
      waves always normalized (P <.001). Baseline QRS width was broader in ER group
      patients with persistent J waves (90 ms vs 80 ms; P = .003) and was unchanged
      with isoproterenol (90 ms; P = .19), whereas it decreased in the remaining
      patients (75 ms; P <.001). CONCLUSIONS: J-wave syndromes have distinct regional
      sensitivity to beta-adrenergic stimulation. J waves may persist in a subset of
      patients with right precordial and inferior J waves but never in lateral
      location. This heterogeneous response to isoproterenol may indicate distinctive
      mechanisms for Brugada and ER patterns, including depolarization abnormalities or
      ion channel sensitivity.

PMID- 22864264
TI  - Going viral: next-generation sequencing applied to phage populations in the human
      gut.
AB  - Over the past decade, researchers have begun to characterize viral diversity
      using metagenomic methods. These studies have shown that viruses, the majority of
      which infect bacteria, are probably the most genetically diverse components of
      the biosphere. Here, we briefly review the incipient rise of a phage biology
      renaissance, which has been catalysed by advances in next-generation sequencing.
      We explore how work characterizing phage diversity and lifestyles in the human
      gut is changing our view of ourselves as supra-organisms. Finally, we discuss how
      a renewed appreciation of phage dynamics may yield new applications for phage
      therapies designed to manipulate the structure and functions of our gut
      microbiomes.

PMID- 22864266
TI  - Remote monitoring of cardiovascular devices: a time and activity analysis.
AB  - BACKGROUND: Expanding indications for cardiovascular implantable electronic
      devices are accompanied by an increasing burden of device clinic follow-up.
      Remote monitoring (RM) may be less time-consuming compared to in-office follow
      up; however, its effect on the device clinic workflow has not been clarified.
      OBJECTIVE: To determine the impact of RM on device clinic workflow. METHODS:
      Detailed workflow data were prospectively collected over a 2-week period in a
      busy device clinic. RESULTS: Five hundred remote transmissions were received from
      434 patients between March 1 and March 16, 2011--346 implantable cardioverter
      defibrillator, 84 pacemaker, and 70 implantable loop recorder transmissions--on 4
      RM platforms (CareLink 56.4%, Merlin.net 21.4%, LATITUDE 17.8%, and Home
      Monitoring 4.4%). The mean time spent per transmission was 11.5 +/- 7.7 minutes,
      which was less than in-person interrogations (27.7 +/- 9.9 minutes; P <.01). Of
      500 transmissions, 135 (27.0%) demonstrated clinically important findings;
      however, only 41 (8.2%) were forwarded for physician review. Of 500
      transmissions, 138 (27.6%) were unscheduled, and these were more likely to
      contain a clinically important event (56 of 138 [40.6%] vs 79 of 362 [21.8%]; P =
      .0001). A total of 5.8% of the transmissions were duplicate. Transmissions that
      revealed clinically important findings took longer to process than those that did
      not (21.0 +/- 7.4 minutes vs 10.1 +/- 2.1 minutes; P <.05). A total of 49.2% of
      the scheduled remote transmissions were missed because of patient noncompliance.
      Telephone follow-up of patients (mean 21 patients/d) who missed scheduled remote
      transmissions took a mean of 55.1 (range 20-98) min/d. CONCLUSIONS: Analysis of
      RM transmissions has significant implications for the device clinic workflow.
      Nonactionable transmissions are rapidly processed, allowing clinicians to focus
      on clinically important findings. However, poor patient compliance complicates
      the workflow efficiency of currently available systems.

PMID- 22864267
TI  - Simulation of prompt gamma-ray emission during proton radiotherapy.
AB  - The measurement of prompt gamma rays emitted from proton-induced nuclear
      reactions has been proposed as a method to verify in vivo the range of a clinical
      proton radiotherapy beam. A good understanding of the prompt gamma-ray emission
      during proton therapy is key to develop a clinically feasible technique, as it
      can facilitate accurate simulations and uncertainty analysis of gamma detector
      designs. Also, the gamma production cross-sections may be incorporated as prior
      knowledge in the reconstruction of the proton range from the measurements. In
      this work, we performed simulations of proton-induced nuclear reactions with the
      main elements of human tissue, carbon-12, oxygen-16 and nitrogen-14, using the
      nuclear reaction models of the GEANT4 and MCNP6 Monte Carlo codes and the
      dedicated nuclear reaction codes TALYS and EMPIRE. For each code, we made an
      effort to optimize the input parameters and model selection. The results of the
      models were compared to available experimental data of discrete gamma line cross
      sections. Overall, the dedicated nuclear reaction codes reproduced the
      experimental data more consistently, while the Monte Carlo codes showed larger
      discrepancies for a number of gamma lines. The model differences lead to a
      variation of the total gamma production near the end of the proton range by a
      factor of about 2. These results indicate a need for additional theoretical and
      experimental study of proton-induced gamma emission in human tissue.

PMID- 22864268
TI  - The gamma distribution model for pulsed-field gradient NMR studies of molecular
      weight distributions of polymers.
AB  - Self-diffusion in polymer solutions studied with pulsed-field gradient nuclear
      magnetic resonance (PFG NMR) is typically based either on a single self-diffusion
      coefficient, or a log-normal distribution of self-diffusion coefficients, or in
      some cases mixtures of these. Experimental data on polyethylene glycol (PEG)
      solutions and simulations were used to compare a model based on a gamma
      distribution of self-diffusion coefficients to more established models such as
      the single exponential, the stretched exponential, and the log-normal
      distribution model with regard to performance and consistency. Even though the
      gamma distribution is very similar to the log-normal distribution, its NMR signal
      attenuation can be written in a closed form and therefore opens up for increased
      computational speed. Estimates of the mean self-diffusion coefficient, the
      spread, and the polydispersity index that were obtained using the gamma model
      were in excellent agreement with estimates obtained using the log-normal model.
      Furthermore, we demonstrate that the gamma distribution is by far superior to the
      log-normal, and comparable to the two other models, in terms of computational
      speed. This effect is particularly striking for multi-component signal
      attenuation. Additionally, the gamma distribution as well as the log-normal
      distribution incorporates explicitly a physically plausible model for
      polydispersity and spread, in contrast to the single exponential and the
      stretched exponential. Therefore, the gamma distribution model should be
      preferred in many experimental situations.

PMID- 22864269
TI  - Concentrations of thyroid axis hormones in psychotic patients on hospital
      admission: the effects of prior drug use.
AB  - The aim of this study was to determine the concentrations of thyroid axis
      hormones in psychotic patients on hospital admission and to search for the
      associations between the concentrations of these hormones and prior drug use as
      well as mental symptoms. MATERIAL AND METHODS. Psychiatric diagnoses,
      psychotropic drug use, and the severity of psychoses were evaluated using the
      standard methods on admission. Venous blood from patients and healthy controls
      was drawn for the analysis of free thyroxin (FT(4)), free triiodothyronine
      (FT(3)), thyroid-stimulating hormone (TSH), and sex hormone-binding globulin
      (SHBG) concentrations. RESULTS. Eighty-one psychotic patients, free of a thyroid
      disorder, were enrolled into the study. Compared with the controls, they
      displayed the higher FT(4) concentrations in the general group (P=0.003) and the
      higher SHBG concentrations only in men (P=0.013). The FT(4) concentration was
      higher in the patients who were not taking an antipsychotic drug on admission
      (P=0.039). No significant correlation was found between the severity of psychosis
      and concentrations of thyroid axis hormones. However, the FT(3) concentration in
      the general group and TSH concentration in women correlated with the factor of
      the Brief Psychiatric Rating Scale expressing elevated mood. CONCLUSIONS. Our
      study confirms the higher FT(4) concentrations in a significant proportion of
      acute psychotic patients. The concentrations of thyroid axis hormones were found
      to be associated with prior antipsychotic treatment on hospital admission.

PMID- 22864270
TI  - Cognitive evaluation of bupropion sustained release in heavy tobacco smokers
      using event-related potentials.
AB  - OBJECTIVE. The aim of this study was to investigate the effects of bupropion
      sustained release (SR) on cognitive function, evaluated by event-related
      potentials (ERPs), in heavy tobacco smokers. MATERIAL AND METHODS. A total of 10
      healthy volunteers (6 men and 4 women) were enrolled into the study. P3a and P3b
      components were evaluated by the novelty P3 paradigm. The ERP recordings were
      taken after the overnight abstaining and the first dose on the 1st day, on the
      7th day, and 45th day of the therapy. RESULTS. The analysis of
      electrophysiological data in response to the standard stimuli in the parietal
      area after 7-day bupropion SR treatment revealed a significant increase in the P2
      latency (P<0.05). With respect to the drug use * topography effect, an increasing
      trend of borderline significance in the P3b and P2 amplitudes against target
      events in the parietal area was observed (P=0.08 for both). A significant
      increase in the P3a amplitude in the parietocentral area was also observed on the
      seventh day of treatment (P<0.05). CONCLUSIONS. The reduction of P3a in the
      frontal area may be due to the decreased distractibility of task-irrelevant novel
      events, which may mean an augmentation of focused attention to task-relevant
      target events. The increases in the P3b and P2 amplitudes for target events in
      the parietal area are very suggestive of this hypothesis, since these components
      reflect the response to task-relevant target events. Meanwhile, the increased P2
      latency for standard events may reflect reduced attention resources for the
      processing of standard events due to increased attention resources allocated for
      task-relevant target events. Decreased distractibility and increased attention
      are believed to be caused by bupropion.

PMID- 22864271
TI  - Clinicopathological features of Churg-Strauss syndrome with severe nerve
      degeneration: a case report.
AB  - Churg-Strauss syndrome (CSS) is a rare autoimmune vasculitis of unknown etiology
      that involves small- and medium-sized blood vessels. Its onset is thought to be
      associated with adult-onset asthma, and vasculitis typically involves vessels in
      the lungs. However, due to increased blood and tissue eosinophilia, vasculitis
      may result in the involvement multiple systems of (neurological, skin, etc.). We
      report a case of CSS with manifestations that included skin purpura and severe
      peripheral nerve degeneration in a 56-year-old woman with a recent history of
      asthma. After the treatment with methylprednisolone and standard
      immunosuppressive therapy, her rashes resolved, there were no acute asthma
      attacks, and the numbness in her lower limbs improved.

PMID- 22864272
TI  - Mitochondrial membrane barrier function as a target of hyperthermia.
AB  - BACKGROUND AND OBJECTIVE. Hyperthermia is a promising modality for cancer
      treatment that urgently requires detailed knowledge on molecular and cellular
      processes for the rational development of treatment protocols. The thorough study
      of the response of the inner membrane of heart and liver mitochondria to
      hyperthermia was performed in order to establish the pattern of the hyperthermia
      induced changes in the membrane barrier function. MATERIAL AND METHODS. The
      isolated mitochondria from rat heart and liver (of both genders) were used for
      experiments, as well as mitochondria isolated from the perfused male rat liver.
      Changes in the membrane permeability were evaluated by mitochondrial respiration
      in state 2 or by estimation of the modular kinetics of the membrane leak.
      RESULTS. The inner membrane of isolated mitochondria from healthy tissues was
      found to be an extremely sensitive target of hyperthermia that exerted the
      response even in the febrile range. More severe hyperthermia compromised the
      inner mitochondrial membrane function; however, this response was tissue-specific
      and, to some extent, gender-dependent (for liver mitochondria). The data obtained
      by direct heating of isolated mitochondria were validated by experiments on the
      perfused liver. CONCLUSIONS. The obtained results imply a crucial importance of
      the evaluation of the tissue- and gender-specific differences while developing or
      improving the protocols for hyperthermic treatment or combinatory therapy.

PMID- 22864273
TI  - The effect of nanoparticles in rats during critical periods of pregnancy.
AB  - BACKGROUND AND OBJECTIVE. Nanotechnology works with substances at a nanometer
      scale, and it offers many solutions for biomedicine. Nanoparticles (NPs) have
      been shown as effective agents for imaging, drug delivery, pathogen detection,
      etc. However, to date, NP toxicity is poorly known. The aim of our study was to
      investigate the embryotoxicity and teratogenicity of quantum dots (QDs) at the
      different stages of rat embryogenesis. MATERIALS AND METHODS. Wistar rats were
      injected with CdSe/ZnS or CdTe QDs on the 6th, 13th, and 18th days of
      embryogenesis. Cyclophosphamide was chosen as a positive control of
      embryotoxicity. On the 21st day, the number of resorptions, weight, length, and
      external malformations of the embryos were estimated. Fluorescence spectroscopy
      and microscopy analysis were used to determine the accumulation of QDs in the
      tissues. RESULTS. Exposure to cyclophosphamide during the pregnancy decreased the
      embryonic weight and length when compared with the control group and produced
      numerous malformations. The effects depended on the stage of embryogenesis.
      Meanwhile, QDs did not cause any embryotoxic or teratogenic effects. However,
      CdTe QDs induced necrosis in the tissues of the peritoneal cavity. The necrotic
      tissues contained QDs with altered spectroscopic properties. Spectroscopic and
      microscopic tissue examination revealed that QDs accumulated in the placenta, but
      no penetration to the embryonic tissues was observed. CONCLUSIONS. QDs did not
      cause any direct embryotoxic or teratogenic effects, but they had adverse effects
      on the maternal organism. The observed QD effects and the long-term accumulation
      of QDs in the maternal organism may increase the risk of adverse effects on
      embryo development.

PMID- 22864274
TI  - EuroPrevall survey on prevalence and pattern of self-reported adverse reactions
      to food and food allergies among primary schoolchildren in Vilnius, Lithuania.
AB  - The aim of the research was to assess the prevalence and pattern of self-reported
      adverse reactions to food and food allergies among primary schoolchildren in
      Vilnius. MATERIAL AND METHODS. Vilnius University was a partner in the
      EuroPrevall project. A total of 4333 schoolchildren from 13 primary schools
      participated in the study. Of all 4333 questionnaires distributed, 3084 were
      returned (response rate, 71.2%). This screening phase was followed by the second
      (clinical) part with an objective confirmative laboratory analysis of blood
      samples for the diagnosis of food allergy. For the research purposes, 186 blood
      samples for IgE were analyzed. RESULTS. Almost half of the children had an
      illness or a disorder caused by eating food. The prevalence of adverse reactions
      to food was found to be increasing with age from 6 to 10 years. Food allergy was
      diagnosed in 16.4% of children. Boys had food allergy more frequently than girls.
      Diarrhea or vomiting and a rash, urticarial rash, or itchy skin were the most
      commonly mentioned symptoms. Fruits, berries, and milk and dairy were found to be
      the most common foods to cause adverse reactions. The most relevant foods for
      children with IgE-mediated food allergy were cow's milk and hazelnuts.
      CONCLUSIONS. The prevalence of self-reported food hypersensitivity among primary
      schoolchildren was observed in almost half of the studied population. Fruits,
      berries, and milk and dairy were the most common foods to cause adverse reactions
      among primary schoolchildren in Lithuania. The determined differences in the
      prevalence of food hypersensitivity and IgE-mediated food allergy and
      associations with gender and age need further scientific analysis for the
      development of prognostic and diagnostic tools.

PMID- 22864275
TI  - Survival of women with breast cancer in Kaunas Region, Lithuania.
AB  - OBJECTIVE. The assessment of breast cancer survival rates and comparison with
      those of other countries may help to deepen knowledge among decision makers in
      the health care system and to improve the inequalities in accessibility to early
      detection and effective treatment. The aim of this study was to evaluate breast
      cancer survival rates in Kaunas region, Lithuania, and to compare them with those
      in the selected European countries. MATERIAL AND METHODS. A retrospective study
      was carried out using medical records and data gathered from the Lithuanian
      Cancer Registry. A group of 240 patients with primary breast cancer diagnosed in
      2008 in Kaunas region was analyzed. All causes of death were included in the
      analysis. The closing date of follow-up was September 30, 2010. Survival was
      determined using the life-table method and the Kaplan-Meier method. Cox
      proportional hazard models were used to estimate the effects of prognostic risk
      factors on survival. RESULTS. The median age of the patients was 63 years (range,
      28-95). The 1-year and 2-year cumulative survival for breast cancer patients in
      Kaunas region, Lithuania, was 94.2% and 90.1%, respectively. As expected, the
      survival of patients with diagnosed advanced disease (stage III and IV) was
      significantly worse than that of patients with stage I (P<0.001) and II (P=0.003)
      disease. The screening group (aged 50-69 years) showed better survival in
      comparison with the group older than 69 years. Age, T4 tumor, and distant
      metastasis were the prognostic factors significantly associated with an increased
      relative mortality risk of breast cancer. CONCLUSIONS. Compared to the European
      survival rates, the 1-year and 2-year survival of patients with breast cancer in
      Lithuania was found to be similar to most European countries.

PMID- 22864276
TI  - An unusual case of a sore throat and otalgia in a 4-year-old boy.
AB  - A sore throat, otalgia, and snoring are the common symptoms seen in children
      presenting to an otorhinolaryngological clinic. Sometimes, however, these
      symptoms may be suggestive of an aggressive malignancy. We present a rare case of
      Burkitt's lymphoma of the tonsil in a young child, which initially manifested as
      a sore throat and otalgia.

PMID- 22864277
TI  - Virtual histology findings and effects of varying doses of atorvastatin on
      coronary plaque volume and composition in statin-naive patients: the VENUS study.
AB  - BACKGROUND: While statin induces plaque regression, its effects, particularly
      with different doses on plaque virtual histology composition, remain unknown.
      METHODS AND RESULTS: In this prospective, randomized, double-blinded study, 40
      consecutive statin-naive patients with stable angina requiring percutaneous
      coronary intervention (PCI) were randomized to 2 arms (20 patients each)
      receiving 6 months of atorvastatin 10 mg or 40 mg daily. The primary end-point
      was (VH-IVUS) changes from baseline to 6 months, as assessed by a core
      laboratory. Fifty-four VH-IVUS lesions were analyzed from the 10 mg group and 57
      from the 40 mg group. Overall, plaque volume was reduced by 4.28% (-5.10+/-14.93
      mm(3), P<0.001), absolute VH-IVUS fibrous volume by 10.54% (-4.87+/-10.74 mm(3),
      P<0.001), and relative percentage fibrous component by 3.29+/-7.84% (P<0.001),
      while relative percentage dense calcium increased by 1.50+/-3.08% (P<0.001), and
      necrotic core by 3.19+/-7.82% (P<0.001). Beneficial changes were more substantial
      in the higher dose (40 mg) group, with significantly more percentage plaque
      volume regression (-1.50+/-3.85% vs. 0.38+/-4.05% increase in the 10 mg group,
      P=0.014), less relative percentage necrotic core expansion (1.68+/-7.57% vs.
      4.78+/-7.82% in the 10 mg group, P=0.037), and without occurrence of major
      adverse cardiac events (vs. 6 patients in the 10 mg group, P=0.020). CONCLUSIONS:
      In statin-naive patients requiring PCI, 6 months of atorvastatin induced a
      significant percentage of plaque volume reduction and substantial modification of
      VH-IVUS composition. In addition, these effects appeared to vary with different
      doses of atorvastatin, showing significantly better limitation of relative
      percentage necrotic core expansion at a higher dose.

PMID- 22864278
TI  - Contemporary outcomes after endovascular treatment for aorto-iliac artery
      disease.
AB  - BACKGROUND: The patency and complications in aorto-iliac (AI) stenting remain
      poorly understood. The aim of this paper was to investigate the safety and
      efficacy after AI stenting. METHODS AND RESULTS: This study was performed as a
      large-scale multicenter, retrospective registry. A total of 2,147 consecutive
      patients with AI disease were enrolled. The safety endpoints were procedure
      success, complications and 30-day mortality. The efficacy endpoints were primary,
      assisted primary and secondary patency, overall survival, freedom from major
      adverse cardiovascular events (MACE; all-cause death, myocardial infarction and
      stroke), and major adverse cardiovascular and limb events (MACLE; any repeat
      revascularization for limb and leg amputation in addition to MACE). Procedure
      success, complication rate and 30-day mortality were 97.6%, 6.4% and 0.7%.
      Primary patency was 92.5%, 82.6% and 77.5% at 1, 3 and 5 years, assisted primary
      patency was 97.0%, 92.7% and 91.9% at 1, 3 and 5 years and secondary patency was
      99.0%, 98.7% and 98.5% at 1, 3 and 5 years. The overall survival rate was 95.0%,
      87.6%, and 79.3% at 1, 3 and 5 years. The cause of death was cardiovascular in
      44.1%. Freedom from MACE (MACLE) was 93.3% (89.9%), 84.4% (76.7%), and 74.9%
      (66.8%) at 1, 3 and 5 years. Female gender, diabetes, renal failure, absence of
      aspirin, reference vessel diameter <8.0mm and outflow lesion were found to be
      independent predictors of primary patency. CONCLUSIONS: The safety and efficacy
      after AI stenting are feasible compared to surgical reconstruction.

PMID- 22864279
TI  - Experimental and DFT study of thiol-stabilized Pt/CNTs catalysts.
AB  - Using a combination of experiments and density functional theory (DFT)
      calculations, we explored the mechanisms of the stabilization effect of the
      thiolized (-SH) group on the Pt/SH-CNTs catalyst. Pt particles supported on the
      hydroxyl functionalized CNTs (Pt/OH-CNTs) are synthesized as a baseline for
      comparison. Experimentally, the platinum on OH-CNTs has a stronger tendency for
      aggregation than that on SH-CNTs. The differences in the oxidation resistance,
      migration activation energy, and corrosion resistance between the Pt/SH-CNTs and
      Pt/OH-CNTs are calculated using DFT. The DFT calculations indicate that the -SH
      group enhances the oxidation resistance of the Pt cluster and CNTs and restricts
      Pt migration on the CNTs. DFT calculations also suggest that the enhanced
      stability of Pt/SH-CNTs originates from the increased interaction between Pt and
      SH-CNTs and the depressed d-band center of the Pt NPs. Thus, the functional
      groups on the CNTs used for stabilization of supported Pt NPs should provide a
      deposit and anchor site for Pt NPs and maintain the perfect structure of CNTs
      rather than destroying it.

PMID- 22864280
TI  - Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate
      carcinoma?
AB  - MicroRNAs (miRs) are small noncoding RNAs that have been reported to be promising
      diagnostic tools. We used quantitative real-time reverse transcription PCR (RT
      qPCR) to analyze differentially expressed miRNAs in prostate tumor samples to
      determine its prognostic value. From 2007 to 2009, tumor tissues were obtained
      from 73 radical prostatectomy specimens. Differentially expressed miR-96, -145
      and -221 were validated by TaqMan RT-qPCR using all 73 tissues. The prognostic
      value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox
      regression analyses. For our patient cohort, the mean age was 64.7 years (50-76
      years) and the mean prostate-specific antigen (PSA) was 7.5 ng ml(-1). During the
      follow-up period (mean, 19.4 months), 14 of 73 (19.2%) patients developed
      biochemical recurrence. Expression of miR-96, -145 and -221 correlated strongly
      with each other, but there were no correlations between miRNA expression and
      clinicopathologic parameters. Kaplan-Meier survival curves using the log-rank
      test showed a decreased biochemical recurrence-free interval with pathologic
      stage (P<0.001). In addition, patients with Gleason scores over 8, compared with
      those with a Gleason score of 6, showed a decreased biochemical recurrence-free
      interval in Kaplan-Meier analysis (P=0.001). However, expression of miR-96, -145
      and -221 did not correlate with the biochemical recurrence interval in Kaplan
      Meier survival curves or by multivariate analysis using the Cox proportional
      hazard regression model, either. In conclusion, we did not observe a significant
      correlation between the expression of miR-96, -145 and -221 and clinicopathologic
      parameters. To utilize miRNA as a diagnostic tool in clinical practice, more
      research is needed to understand miRNA mechanisms, identify miRNA targets, and
      further characterize miRNA function.

PMID- 22864281
TI  - Effect of surgical procedures on prostate tumor gene expression profiles.
AB  - Current surgical treatment of prostate cancer is typically accomplished by either
      open radical prostatectomy (ORP) or robotic-assisted laparoscopic radical
      prostatectomy (RALRP). Intra-operative procedural differences between the two
      surgical approaches may alter the molecular composition of resected surgical
      specimens, which are indispensable for molecular analysis and biomarker
      evaluation. The objective of this study is to investigate the effect of different
      surgical procedures on RNA quality and genome-wide expression signature. RNA
      integrity number (RIN) values were compared between total RNA samples extracted
      from consecutive LRP (n=11) and ORP (n=24) prostate specimens. Expression
      profiling was performed using the Agilent human whole-genome expression
      microarrays. Expression differences by surgical type were analyzed by Volcano
      plot analysis and gene ontology analysis. Quantitative reverse transcription (RT)
      PCR was used for expression validation in an independent set of LRP (n=8) and ORP
      (n=8) samples. The LRP procedure did not compromise RNA integrity. Differential
      gene expression by surgery types was limited to a small subset of genes, the
      number of which was smaller than that expected by chance. Unexpectedly, this
      small subset of differentially expressed genes was enriched for those encoding
      transcription factors, oxygen transporters and other previously reported surgery
      induced stress-response genes, and demonstrated unidirectional reduction in LRP
      specimens in comparison to ORP specimens. The effect of the LRP procedure on RNA
      quality and genome-wide transcript levels is negligible, supporting the
      suitability of LRP surgical specimens for routine molecular analysis. Blunted in
      vivo stress response in LRP specimens, likely mediated by CO(2) insufflation but
      not by longer ischemia time, is manifested in the reduced expression of stress
      response genes in these specimens.

PMID- 22864283
TI  - Oscillating bubbles: a versatile tool for lab on a chip applications.
AB  - With the fast development of acoustic and multiphase microfluidics in recent
      years, oscillating bubbles have drawn more-and-more attention due to their great
      potential in various Lab on a Chip (LOC) applications. Many innovative bubble
      based devices have been explored in the past decade. In this article, we first
      briefly summarize current understanding of the physics of oscillating bubbles,
      and then critically summarize recent advancements, including some of our original
      work, on the applications of oscillating bubbles in microfluidic devices. We
      intend to highlight the advantages of using oscillating bubbles along with the
      challenges that accompany them. We believe that these emerging studies on
      microfluidic oscillating bubbles will be revolutionary to the development of next
      generation LOC technologies.

PMID- 22864282
TI  - Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of
      chronic bacterial prostatitis in Chinese patients.
AB  - Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic
      bacterial prostatitis. We investigated the safety and efficacy of levofloxacin
      compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in
      Chinese patients. This was a multicenter, open-label, randomized controlled non
      inferiority trial. Four hundred and seventy-one patients with clinical
      symptoms/signs were enrolled into the study, and 408 patients were
      microbiologically confirmed chronic bacterial prostatitis, who were randomized to
      either oral levofloxacin (500 mg q.d.) or ciprofloxacin (500 mg b.i.d.) for 4
      weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and
      disease recurrence were assessed. The clinical symptoms and signs (including
      dysuria, perineal discomfort or pain) and bacteria cultures in 209 patients
      treated with levofloxacin and 199 patients treated with ciprofloxacin were
      similar. The most common bacteria were Escherichia coli and Staphylococcus
      aureus. One to four weeks after the end of 4 weeks treatment, the bacterial
      clearance rate (86.06% vs. 60.03%; P<0.05) and the clinical efficacy (including
      clinical cure and clinical improvement(93.30% vs. 71.86%; P<0.05)) were
      significantly higher in the levofloxacin-treated group than in the ciprofloxacin
      treated group. The microbiological recurrence rate was significantly lower in the
      levofloxacin-treated group than in the ciprofloxacin-treated group (4.00% vs.
      19.25%; P<0.05). Rates of adverse events and treatment-related adverse events
      were slightly lower in the levofloxacin-treated group than in ciprofloxacin
      treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of
      clinical efficacy and disease recurrence, with a low rate of adverse events, for
      the treatment of chronic bacterial prostatitis in Chinese patients.

PMID- 22864284
TI  - Swimming pool attendance and respiratory symptoms and allergies among Dutch
      children.
AB  - OBJECTIVES: To describe associations among swimming, respiratory health, allergen
      sensitisation and Clara cell protein 16 (CC16) levels in Dutch schoolchildren.
      Trichloramine levels in swimming pool air were determined to assess potential
      exposure levels. METHODS: Respiratory health and pool attendance information was
      collected from 2359 children, aged 6-13 years. Serum from 419 children was tested
      for allergen sensitisation and CC16 levels. Trichloramine levels were assessed in
      nine swimming facilities. RESULTS: Trichloramine levels ranged from 0.03 to 0.78
      mg/m3 (average 0.21 mg/m3). Reported swimming pool attendance and trichloramine
      exposure were both not associated with asthma, wheezing, rhinitis or CC16 levels.
      Birch and house dust mite sensitisation were associated with recent indoor
      swimming (OR>1.86), but not after considering recent swimming frequency
      multiplied by trichloramine levels. Sensitisation to house dust mites was
      associated with frequent baby swimming (ORs=1.75; 95% CI 1.09 to 2.79).
      Furthermore, sensitisation was associated with lower serum CC16 levels. CC16
      levels were associated with average trichloramine concentrations in pools;
      however, not after considering swimming frequency multiplied by trichloramine
      levels. CONCLUSIONS: Measured trichloramine levels were comparable with other
      studies but lower than in an earlier Dutch study. Swimming pool attendance was
      not associated with respiratory symptoms. The association between sensitisation
      and swimming during the first 2 years of life suggests that early-life exposures
      might be important, although this needs further study. The interpretation of
      transient and chronic changes of CC16 and other inflammatory markers in relation
      to the pool environment and health impacts warrants further investigation.
      Detailed comparisons with other studies are limited as few studies have measured
      trichloramine levels.

PMID- 22864285
TI  - Research progress on the mollusc immunity in China.
AB  - The economical and phylogenic importance of mollusc has led an increasing number
      of investigations giving emphasis to immune defense mechanism. This review
      discusses the advances in immunological study of mollusc in China, with special
      reference to dominant aquaculture species over the past decades. As an
      invertebrate group, molluscs lack adaptive immunity and consequently they have
      evolved sophisticated strategies of innate immunity for defense against
      pathogens. This review aims to present the various immunologically significant
      pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs),
      lectins, lipopolysaccharide and beta-1, 3-glucan binding protein (LGBP),
      scavenger receptors (SRs) employed by mollucans. This work also highlights immune
      proteolytic cascade, TLR signaling pathway and an extensive repertoire of immune
      effectors including antimicrobial peptide, lysozyme, antioxidant enzyme and heat
      shock protein. Further, the review presents the preliminary progress made on the
      catecholaminergic neuroendocrine system in scallop and its immunomodulation
      function to throw light into neuroendocrine-immune regulatory network in lower
      invertebrates.

PMID- 22864286
TI  - CuInSe2 ultrathin nanoplatelets: novel self-sacrificial template-directed
      synthesis and application for flexible photodetectors.
AB  - Non-layered chalcopyrite-type CuInSe(2) nanoplatelets, with thickness down to 2
      nm, have been synthesized for the first time. The ultrathin nanoplatelets are of
      benefit for low-cost and high performance flexible photodetectors.

PMID- 22864287
TI  - PHF20 is an effector protein of p53 double lysine methylation that stabilizes and
      activates p53.
AB  - PHF20 is a multidomain protein and subunit of a lysine acetyltransferase complex
      that acetylates histone H4 and p53 but whose function is unclear. Using
      biochemical, biophysical and cellular approaches, we determined that PHF20 is a
      direct regulator of p53. A Tudor domain in PHF20 recognized p53 dimethylated at
      Lys370 or Lys382 and a homodimeric form of this Tudor domain could associate with
      the two dimethylated sites on p53 with enhanced affinity, indicating a
      multivalent interaction. Association with PHF20 promotes stabilization and
      activation of p53 by diminishing Mdm2-mediated p53 ubiquitylation and
      degradation. PHF20 contributes to upregulation of p53 in response to DNA damage,
      and ectopic expression of PHF20 in different cell lines leads to phenotypic
      changes that are hallmarks of p53 activation. Overall our work establishes that
      PHF20 functions as an effector of p53 methylation that stabilizes and activates
      p53.

PMID- 22864288
TI  - Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer.
AB  - The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein
      (Env) spike is a molecular machine that mediates virus entry into host cells and
      is the sole target for virus-neutralizing antibodies. The mature Env spike
      results from cleavage of a trimeric glycoprotein precursor, gp160, into three
      gp120 and three gp41 subunits. Here, we describe an ~11-A cryo-EM structure of
      the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and
      three gp41 subunits form a cage-like structure with an interior void surrounding
      the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane
      region, the torus-like gp41 ectodomain and a trimer-association domain of gp120
      composed of the V1, V2 and V3 variable regions. The cage-like architecture, which
      is unique among characterized viral envelope proteins, restricts antibody access,
      reflecting requirements imposed by HIV-1 persistence in the host.

PMID- 22864290
TI  - Impact of stress hyperglycemia on myocardial salvage following successfully
      recanalized primary acute myocardial infarction.
AB  - BACKGROUND: Elevated blood glucose on admission may worsen outcome after acute
      myocardial infarction (AMI). No relationship has been identified between
      admission blood glucose level and myocardial salvage in patients with AMI.
      METHODS AND RESULTS: This study assessed 150 consecutive patients with a first
      AMI who underwent percutaneous coronary intervention within 24 h from onset of
      symptoms. Plasma blood glucose was measured on admission. Stress hyperglycemia
      was defined as blood glucose >=10 mmol/L (180 mg/dl). The extent of myocardial
      salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance
      imaging (CMRI) as the difference between areas of myocardium at risk (T2-weighted
      hyperintense lesion) and areas of late gadolinium enhancement. The association
      between stress hyperglycemia and myocardial salvage index (MSI) was investigated
      in patients with and without diabetes. Among non-diabetic patients, MSI was lower
      in those with stress hyperglycemia than in those without. No significant
      difference in MSI was noted between diabetes patients with or without stress
      hyperglycemia. On multivariate analysis, stress hyperglycemia in patients without
      diabetes was an independent predictor of MSI. CONCLUSIONS: Stress hyperglycemia
      affects MSI, indicating that the manipulation of glucose levels could be a
      potential therapeutic target for salvaging ischemic damage.

PMID- 22864291
TI  - Human heterotaxy syndrome - from molecular genetics to clinical features,
      management, and prognosis - .
AB  - Human heterotaxy syndrome is characterized by a wide variety of cardiac and
      extracardiac congenital malformations that are primarily induced by disorders of
      the left-right axis determination during early embryonic development. The
      cellular and molecular mechanisms of the left-right asymmetry have been
      extensively investigated in the past decade and the developmental mechanisms of
      the syndrome have been considerably elucidated. Medical and surgical management
      and treatment of heterotaxy syndrome have advanced as well. However, prognosis of
      the disease still remains unsatisfactory because the syndrome is often associated
      with a combination of complicated congenital heart diseases. Management of
      heterotaxy patients, particularly those who have undergone the Fontan procedure,
      is now one of the most important issues in pediatric and adult congenital heart
      disease clinics. In this review, we focus on the recent advances in knowledge of
      the genetic and molecular pathogenesis of heterotaxy syndrome, as well as its
      clinical features, management, and prognosis.

PMID- 22864292
TI  - Preventing bad behavior in the workplace.

PMID- 22864289
TI  - DDR complex facilitates global association of RNA polymerase V to promoters and
      evolutionarily young transposons.
AB  - The plant-specific DNA-dependent RNA polymerase V (Pol V) evolved from Pol II to
      function in an RNA-directed DNA methylation pathway. Here, we have identified
      targets of Pol V in Arabidopsis thaliana on a genome-wide scale using ChIP-seq of
      NRPE1, the largest catalytic subunit of Pol V. We found that Pol V is enriched at
      promoters and evolutionarily recent transposons. This localization pattern is
      highly correlated with Pol V-dependent DNA methylation and small RNA
      accumulation. We also show that genome-wide chromatin association of Pol V is
      dependent on all members of a putative chromatin-remodeling complex termed DDR.
      Our study presents a genome-wide view of Pol V occupancy and sheds light on the
      mechanistic basis of Pol V localization. Furthermore, these findings suggest a
      role for Pol V and RNA-directed DNA methylation in genome surveillance and in
      responding to genome evolution.

PMID- 22864293
TI  - Doing more with less: using core values and standards of holistic nursing to
      expand practice in an era of shrinking resources.

PMID- 22864294
TI  - Cultural competency in baccalaureate US nursing education: hybrid course.
AB  - The ability to appropriately care for diverse populations is an expected
      competency of the graduated Bachelor of Science in Nursing (BSN). To provide
      effective materials to ensure this competency is met, the American Association of
      Colleges of Nursing developed the Toolkit of Resources for Cultural Competent
      Education for Baccalaureate Nurses. The toolkit provides information on cultural
      competency models and teaching strategies nurse educators can use to facilitate
      student learning in cultural sensitivity and competency. This article
      demonstrates how one model in particular, Campinha-Bacote's Model of Cultural
      Competence, was utilized for 15 weeks in an undergraduate BSN nursing course for
      a student population in an urban school of nursing to effectively provide
      students with the skill set needed to give culturally competent care. This
      article will provide the methods and strategies used to teach cultural competency
      as based on Campinha-Bactote's Model in an undergraduate nursing course.

PMID- 22864295
TI  - Ethical leadership.
AB  - In today's climate and environment, the conventional relationship between caring,
      economic, and administrative practices no longer serves the interest of patients,
      clinicians, or systems. A shift toward human caring values and an ethic of
      authentic healing relationships is required as systems now have to value human
      resources and life purposes, inner meaning, and processes for providers and
      patients alike. The costs of unethical behavior can be even greater for
      followers. When we assume the benefits of leadership, we also assume ethical
      burdens. It is the assertion and experience of the author that the triangle of
      ethics and ethical behavior, followers, and patient's outcomes are closely
      interrelated and affect each other in a very intimate and direct way. Unethical
      leadership may lead to follower disappointment and distrust, leading to lack of
      interest and commitment, consequently negatively impacting patient outcomes and
      organizational effectiveness.

PMID- 22864297
TI  - Promoting student success and well-being: a stress management course.
AB  - Nursing students need to be prepared for a highly complex and challenging
      profession. This article describes an experiential course where students learn
      stress management skills and develop a stress management plan. These skills can
      be used during their nursing education and then transferred to clinical practice.

PMID- 22864296
TI  - Yoga for youth in pain: the UCLA pediatric pain program model.
AB  - Children, adolescents, and young adults do not typically feature in clinics,
      studies, and mainstream notions of chronic pain. Yet many young people experience
      debilitating pain for extended periods of time. Chronic pain in these formative
      years may be especially important to treat in order for young patients to
      maintain life tasks and to prevent protracted disability. The Pediatric Pain
      Program at the University of California, Los Angeles, is a multidisciplinary
      treatment program designed for young people with chronic pain and their families.
      We offer both conventional and complementary medicine to treat the whole
      individual. This article describes the work undertaken in the clinic and our
      newly developed Yoga for Youth Research Program. The clinical and research
      programs fill a critical need to provide service to youth with chronic pain and
      to scientifically study one of the more popular complementary treatments we
      offer, Iyengar yoga.

PMID- 22864298
TI  - Awareness of advance directives among Korean nurses.
AB  - Awareness of advance directives (AD) among 293 nurses working in acute hospitals
      was evaluated through a structured questionnaire. Nurses were poorly acquainted
      with AD. Education about AD and related concepts are required in college and
      field experience to improve practice and communication with patients at the end
      of life.

PMID- 22864299
TI  - African Geranium (EPs 7630), part 2: the efficacy of Pelargonium sidoides (EPs
      7630) in the treatment of acute bronchitis in adults and children.

PMID- 22864300
TI  - Interaction and reaction of the hydroxyl ion with beta-D-galactose and its
      hydrated complex: an ab initio molecular dynamics study.
AB  - The interaction of OH(-) with the sugar beta-D-galactose is studied
      computationally, with Ab Initio Molecular Dynamics (AIMD) as the prime tool. The
      main findings are: (1) the OH(-) abstracts a proton from the sugar in a barrier
      less process, yielding H(2)O and a Deprotonated beta-d-Galactose anion, (Dep-beta
      D-G)(-). (2) This reaction can be reversed when two additional H(2)O molecules
      are present in the sugar. (3) At 500 K, a ring-opening reaction occurs in (Dep
      beta-D-G)(-) within a timescale of 10 ps. The (neutral) sugar itself is stable
      over this timescale, and well beyond. This indicates that OH(-) can catalyze the
      degradation of beta-d-galactose. Implications of this process are briefly
      discussed.

PMID- 22864301
TI  - Impaired regulatory function and enhanced intrathecal activation of B cells in
      neuromyelitis optica: distinct from multiple sclerosis.
AB  - BACKGROUND: The effective treatment of neuromyelitis optica (NMO) with rituximab
      has suggested an important role for B cells in NMO pathogenesis. OBJECTIVE: To
      explore the antibody-independent function of B cells in NMO and relapsing
      remitting multiple sclerosis (RRMS). METHODS: Fifty-one NMO patients and 42 RRMS
      patients in an acute relapse phase and 37 healthy controls (HC) were enrolled in
      the study. The B cell expression of B cell activating factor receptor (BAFF-R),
      CXCR5 and very late antigen-4 (VLA-4), the B cell production of interleukin (IL)
      10 and interferon (IFN)-gamma and the proportion of circulating memory and
      CD19(+)CD24(high)CD38(high) regulatory B cells were evaluated by flow cytometry.
      The cerebrospinal fluid (CSF) levels of BAFF and CXCL13 were determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: The CD19(+)CD24(high)CD38(high)
      regulatory B cell levels and the B cell expression of IL-10 were significantly
      lower in NMO patients than in RRMS patients and the HC. In aquaporin-4 antibody
      (AQP4-ab)-positive NMO patients, the B cell IL-10 production and
      CD19(+)CD24(high)CD38(high) regulatory B cell levels were even lower than in AQP4
      ab-negative NMO patients. The CSF BAFF and CXCL13 levels were significantly
      higher in NMO patients than in patients with RRMS and other non-inflammatory
      neurologic diseases (ONDs). CONCLUSIONS: The immuno-regulatory properties of B
      cells are significantly impaired in NMO patients and particularly in AQP4-ab
      positive NMO patients. The elevated CSF levels of BAFF and CXCL13 in NMO suggest
      an enhanced intrathecal B cell recruitment and activation. Our results further
      define the distinct immunological nature of NMO and RRMS from the B cell
      perspective.

PMID- 22864303
TI  - Dose findings of antofloxacin hydrochloride for treating bacterial infections in
      an early clinical trial using PK-PD parameters in healthy volunteers.
AB  - AIM: To find an appropriate dose regimen of the novel antibacterial agent
      antofloxacin for a phase II clinical trial using a population pharmacokinetic
      (PPK) study in healthy volunteers and the minimum inhibitory concentration (MIC)
      as pharmacodynamic (PD) parameters. METHODS: Twenty-four healthy volunteers were
      enrolled in a double-blind crossover study and received antofloxacin (200 or 400
      mg/d, po) for consecutive 5 d with 10 d washout between two separate periods.
      Blood concentrations were analyzed using HPLC with a UV-Vis detector. The values
      of area under the curve (AUC) with covariates were obtained from a PPK model, and
      the MICs came from the previous in vitro studies. The dose regimen was determined
      for the phase II clinical trial according to the ratio (>20) of AUC/MIC, and the
      efficacy of the dose was evaluated by the trial. RESULTS: A two-compartment model
      best described the time-concentration data with first-order absorption. The PPK
      parameter estimates for CL, V(c), Q, V(p) and K(A) are 8.34 L/h, 142 L, 15.9 L/h,
      52.2 L and 4.64 1/h, respectively. The covariates sex for K(A), weight for CL,
      weight for V(c) and interoccasion variability were included in the final model.
      The AUC/MIC was calculated based on the PPK model and the MIC of antofloxacin for
      Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus and Staphylococcus
      epidermidis were determined in previous researches. The 400 mg loading dose with
      200 mg/d maintenance dose was recommended and confirmed by the phase II trial.
      CONCLUSION: The ratio of AUC from the PPK model vs MIC as the PD parameter can be
      applied in a dose-finding trial of antofloxacin in treatment of bacterial
      infections. The PPK model suggests that sex and body weight may be considerations
      in regards to individual therapy, which should be investigated in larger clinical
      trials and serve as a potential reference for clinical therapies.

PMID- 22864304
TI  - Effect of tissue heterogeneity on an in vivo range verification technique for
      proton therapy.
AB  - It was proposed recently that time-resolved dose measurements during proton
      therapy treatment by passively scattered beams may be used for in vivo range
      verification. The method was shown to work accurately in a water tank. In this
      paper, we further evaluated the potential of the method for more clinically
      relevant situations where proton beams must pass through regions with significant
      tissue heterogeneities. Specifically, we considered prostate treatment where the
      use of anterior or anterior- oblique fields was recently proposed in order to
      reduce rectal dose by taking advantage of the sharp distal fall-off of the Bragg
      peak. These beam portals pass through various parts of pubic bone and potential
      air cavities in the bladder and bowels. Using blocks of materials with densities
      equivalent to bone, air, etc, arranged in the water tank in relevant
      configurations, we tested the robustness of the method against range shifting and
      range mixing. In the former, the beam range is changed uniformly by changes in
      tissue density in the beam path, while in the latter, variations in tissue
      heterogeneities across the beam cross section causes the mixing of beam energies
      downstream, as often occurs when the beam travels along the interface of
      materials with significantly different densities. We demonstrated that in the
      region of interest, the method can measure water-equivalent path length with
      accuracy better than +/-0.5 mm for pure range shifting and still reasonable
      accuracy for range mixing between close beam energies. In situations with range
      mixing between significantly different beam energies, the dose rate profiles may
      be simulated for verifying the beam range. We also found that the above
      performances can be obtained with very small amount of dose (<0.5 cGy), if
      silicon diodes are used as detectors. This makes the method suitable for in vivo
      range verification prior to each treatment delivery.

PMID- 22864305
TI  - Shoulder injury.

PMID- 22864302
TI  - Ionotropic receptors and ion channels in ischemic neuronal death and dysfunction.
AB  - Loss of energy supply to neurons during stroke induces a rapid loss of membrane
      potential that is called the anoxic depolarization. Anoxic depolarizations result
      in tremendous physiological stress on the neurons because of the dysregulation of
      ionic fluxes and the loss of ATP to drive ion pumps that maintain electrochemical
      gradients. In this review, we present an overview of some of the ionotropic
      receptors and ion channels that are thought to contribute to the anoxic
      depolarization of neurons and subsequently, to cell death. The ionotropic
      receptors for glutamate and ATP that function as ligand-gated cation channels are
      critical in the death and dysfunction of neurons. Interestingly, two of these
      receptors (P2X7 and NMDAR) have been shown to couple to the pannexin-1 (Panx1)
      ion channel. We also discuss the important roles of transient receptor potential
      (TRP) channels and acid-sensing ion channels (ASICs) in responses to ischemia.
      The central challenge that emerges from our current understanding of the anoxic
      depolarization is the need to elucidate the mechanistic and temporal
      interrelations of these ion channels to fully appreciate their impact on neurons
      during stroke.

PMID- 22864306
TI  - Collecting patient data will help UK become world leader in research, says
      Cameron.

PMID- 22864307
TI  - GMC is asked to draw up clearer rules for pathologists carrying out postmortem
      examinations.

PMID- 22864308
TI  - Doctors lobby against closure of US agency that advises on effective health care.

PMID- 22864309
TI  - Private sector run hospital made L2.3m loss in first quarter.

PMID- 22864310
TI  - Are valence and social avoidance associated with the memory conformity effect?
AB  - Pairs of participants were shown photographs which varied in terms of valence
      from negative to positive, and two days later, together, they were given a memory
      recognition test. When the first person responded the second person saw the
      response. This affected how the second person responded, what is called memory
      conformity. The memory conformity effect was larger for previously unseen stimuli
      (fillers) than for previously seen stimuli (targets), and was greatest for those
      with low scores on a social avoidance measure. While memory for negative (and
      most arousing) stimuli was most accurate, the memory conformity effect did not
      differ significantly by the stimulus valence. Implications for theories of memory
      malleability and for assessing the reliability of memories in a forensic context
      are discussed.

PMID- 22864311
TI  - Only correlated sequences that are actively processed contribute to implicit
      sequence learning.
AB  - The purpose of the study was to investigate how implicit sequence learning is
      affected by the presence of secondary information that is correlated with the
      primary sequence but not necessarily relevant to performance. In a previous work,
      we have shown that correlation plays an important role but other prerequisites
      may also be involved. In Experiments 1 and 2, using a task sequence learning
      paradigm, we found that primary sequence learning was not affected by secondary
      information that was sequenced but irrelevant to performance, even though the two
      streams of information were correlated. In contrast, in Experiment 3, we found
      that sensitivity to the main sequence was greater with the provision of extra
      sequenced information that was relevant to performance in addition to being
      correlated. This suggests that sequence learning was enhanced through the
      integration of information. We conclude that information in secondary as well as
      primary sequences must be actively processed if it is to have a beneficial
      impact. By actively processed we mean information that is selectively attended
      and necessary for carrying out the tasks.

PMID- 22864312
TI  - Automatic imitation and spatial compatibility in a key-pressing task.
AB  - Automatic imitation has been often confounded with spatial compatibility effects.
      Heyes (2011) called attention to this confound, and proposed some criteria which
      must be satisfied before these effects could be unequivocally taken to be an
      index of the functioning of the human mirror system. Evidence satisfying such
      criteria has been reported by Catmur and Heyes (2011), using a relatively
      unfamiliar finger abduction movement. However, because many previous studies
      relied on more familiar actions, we aimed at testing whether analogous effects
      could be obtained with a more practiced key-pressing task. In Experiment 1, we
      used anatomical controls (i.e., views of right vs. left hands) under conditions
      affording mirror imitation, and showed that spatial compatibility masked the
      effects of automatic imitation. Experiment 2 used rotated conditions to control
      for this spatial-anatomical confound, and it showed unequivocal effects of
      automatic imitation, which were obtained regardless of its relation to the
      spatial stimulus-response mapping. These results cast some doubts on the
      interpretation of previous reports relying exclusively on scenes presented from a
      mirror perspective, and suggest the convenience of using both rotated scenes and
      anatomical controls in order to assess automatic imitation.

PMID- 22864313
TI  - Timing the moment of impact in fast human movements.
AB  - The reported resolution of timing the moment of impact in fast human movements
      differs widely depending on the task. Surprisingly, better timing is reported for
      the demanding task of batting a ball than for the much simpler task of tapping in
      synchrony with two hands. We wondered whether this is because a sizeable part of
      timing variability arises from misjudging the distance in the direction of one's
      own movement, so that moving faster (as the bat does when moving toward a ball)
      improves timing. We found that moving faster does indeed improve timing in both
      the above-mentioned tasks. After removing the proposed contribution of misjudging
      the distance in the direction of one's own movement, we estimated that the
      remaining standard deviation in timing is just over 6ms for both tasks.

PMID- 22864314
TI  - Nuclear deformation during breast cancer cell transmigration.
AB  - Metastasis is the main cause of cancer mortality. During this process, cancer
      cells dislodge from a primary tumor, enter the circulation and form secondary
      tumors in distal organs. It is poorly understood how these cells manage to cross
      the tight syncytium of endothelial cells that lines the capillaries. Such
      capillary transmigration would require a drastic change in cell shape. We have
      therefore developed a microfluidic platform to study the transmigration of cancer
      cells. The device consists of an array of microchannels mimicking the confined
      spaces encountered. A thin glass coverslip bottom allows high resolution imaging
      of cell dynamics. We show that nuclear deformation is a critical and rate
      limiting step for transmigration of highly metastatic human breast cancer cells.
      Transmigration was significantly reduced following the treatment with a protein
      methyltransferase inhibitor, suggesting that chromatin condensation might play an
      important role. Since transmigration is critical for cancer metastasis, this new
      platform may be useful for developing improved cancer therapies.

PMID- 22864315
TI  - Long pentraxin-3 measured at late phase associated with GRACE risk scores in
      patients with non-ST elevation acute coronary syndrome and coronary stenting.
AB  - OBJECTIVES: We analyzed pentraxin 3 (PTX3) levels and the relation of PTX3 levels
      with GRACE risk scores in 39 patients with non-ST elevation acute coronary
      syndrome (ACS) and stabile angina after stenting. STUDY DESIGN: Seventeen
      patients with ACS and 22 patients with stabile angina who underwent coronary
      stenting were included in the study. PTX3 levels were measured serially at
      admission, at the 8th hour and at the 24th hour after stenting. RESULTS: While
      diabetes and hypertension were more frequent in the stabile angina group,
      leukocyte counts were significantly higher in the ACS group. PTX3 levels measured
      at the 8th hour were significantly higher in the ACS group compared to the
      stabile angina group (p=0.003). Strong correlations were observed between 24th
      hour PTX3 levels and GRACE scores calculated for risk of death and death/MI at
      admission (in-hospital/to 6 months), and for risk of death/MI at discharge to 6
      months (R=0.571, p=0.01, R=0.564, p=0.01; R=0.558, p=0.02, R=0.512, p=0.03;
      R=0.653, p=0.004, respectively). CONCLUSION: The serum PTX3 levels may provide
      important information for the early risk stratification of patients with ACS who
      underwent coronary stenting.

PMID- 22864316
TI  - The importance of fragmented QRS complexes in prediction of myocardial infarction
      and reperfusion parameters in patients undergoing primary percutaneous coronary
      intervention.
AB  - OBJECTIVES: The QRS complex fragmentations (fQRS) frequently seen on admission
      electrocardiograms (ECGs) with narrow or wide QRS complex are associated with
      increased morbidity and mortality. The causative relationship between fQRS and
      cardiac fibrosis is known, but the relation of fragmented QRS before and after
      primary percutaneous coronary intervention (p-PCI) with myocardial infarction and
      reperfusion parameters has not been studied until now. STUDY DESIGN: The study
      included 184 consecutive patients with ST elevation myocardial infarction (STEMI)
      who underwent p-PCI. Presence or absence of fQRS on pre- and post-PCI ECGs and
      its change following PCI were investigated. In addition, independent predictors
      of fQRS were also investigated. Patients with significant organic valve disease
      and patients having any QRS morphology with QRS duration ?120 ms as well as
      patients with permanent pacemakers were excluded from the study. RESULTS:
      Patients with fQRS on admission ECG had higher leukocyte counts (p=0.001), higher
      CK-MB (p=0.001) and troponin levels (p=0.005), increased pain to balloon time
      (p=0.004), higher Killip score (p<0.001), prolonged QRS time (p<0.001), higher
      Gensini score (p<0.001) and more frequent Q waves on ECG (p<0.001) in comparison
      to patients with non-fragmented QRS. In addition, these patients usually had an
      infarction of anterior territory related to a lesion in proximal LAD and wider
      jeopardized myocardium (p<0.001). fQRS was significantly related to infarction
      and myocardial reperfusion parameters before and after p-PCI. In the setting of
      STEMI, absence of fQRS on admission ECG predicted increased ST resolution, higher
      reduction in QRS duration, and better myocardial reperfusion. CONCLUSION: FQRS
      may be useful in identifying patients at higher cardiac risk with larger areas of
      ischemic jeopardized or necrotic myocardium.

PMID- 22864317
TI  - Increased leucocyte count could predict coronary artery calcification in patients
      free of clinically apparent cardiovascular disease.
AB  - OBJECTIVES: Several studies have demonstrated that inflammation plays a major
      role in the development of atherosclerosis and that the inflammatory process
      might also be involved in coronary artery calcification (CAC). The main purpose
      of this study was to investigate the relation between leucocyte count and CAC and
      to determine whether a higher leucocyte count could indicate subclinical
      atherosclerosis in patients without overt cardiovascular disease. STUDY DESIGN: A
      total of 284 consecutive patients (156 men, 128 women) without established
      cardiovascular disease were enrolled. CAC was measured using cardiac computed
      tomography. Leucocyte count was measured via routine blood examination. RESULTS:
      Patients with CAC had higher leucocyte counts compared to those without
      calcification (7.87+/-1.85 vs. 6.01+/-1.84; p<0.001). Logistic regression
      analysis identified the following as independent predictors of CAC: leucocyte
      count (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3-2.1), smoking (OR:
      2.4, 95% CI: 1.2-4.6) and age (OR: 1.2, 95% CI: 1.1-2.3). There was also a
      significant correlation between CAC and leucocyte count (r=0.57, p<0.001).
      CONCLUSION: We demonstrated that leucocytes may play an important role in the
      evolution of CAC and may be used in the detection of subclinical atherosclerosis
      in asymptomatic subjects.

PMID- 22864318
TI  - Impact of severity of congenital heart diseases on university graduation rate
      among male patients.
AB  - OBJECTIVES: This study examines university graduation rates among individuals
      with congenital heart disease (CHD) in comparison to their healthy peers. The
      effect of disease severity, type of surgery, and timing of surgery on graduation
      rate was also evaluated. STUDY DESIGN: One hundred forty-five male patients with
      CHD at military age were enrolled in the study between the dates of January 2005
      and May 2007. Severity of disease was operationalised in term of initial
      diagnosis (According to classification of 32th ACC Bethesta Conference Task Force
      1). University graduation rates of among two groups of CHD patients (mild disease
      (group 1) or moderate to severe disease (group 2)) are compared to each other and
      to healthy peers. RESULTS: Patients with CHD have reduced rates of participation
      in higher education compared with healthy individuals (13.1% vs 20.7%, p=0.01).
      Furthermore, this negative effect on education participation rate is independent
      of the severity of disease (group 1, 16.4%, p=0.01; group 2, 9.7%, p<0.001).
      Although the university graduation rate was relatively higher in patients with
      mild disease severity, no significant difference was found between the two
      patient groups (p=0.23). Having an operation does not effect graduation rate
      (p=0.58), however greater age at the time of operation increases the likelihood
      of graduation (p=0.02). CONCLUSION: Being born with CHD significantly reduces the
      chance of completing higher education. This negative impact on university
      graduation rate is independent of the severity of the disease. No negative
      effects of disease related surgery or subsequent corrective surgery on education
      were observed. Patients who were operated on later in life were more likely to
      complete university education. Mean operation age of this group corresponds to
      the typical age during the last year of elementary school in Turkey.

PMID- 22864319
TI  - [Alterations in pulmonary artery pressure following mitral valve replacement].
AB  - OBJECTIVES: We sought to evaluate the early postoperative hemodynamics and
      clinical aspects in patients with moderate to severe pulmonary artery pressure
      (PAP) who underwent mitral valve replacement (MVR) due to isolated mitral valve
      stenosis. STUDY DESIGN: Fifty patients (33 women, 17 men; mean age 45.8+/-11.2)
      were divided into two groups according to mean PAP levels (PAP <50 mmHg as Group
      I and PAP >50 mmHg as Group II). PAP and pulmonary capillary wedge pressure
      (PCWP) values were recorded using Swan-Ganz catheter just before the surgery in
      the operation theatre. These measurements were repeated after weaning from
      cardiopulmonary bypass, at 1, 12 and 24 hours. Intubation period in the intensive
      care unit, need for inotropic agents in the pre-and postoperative course, and
      mortality and morbidity data were also evaluated. Transthoracic echocardiography
      was used to measure PAP at the postoperative 24th hour and at the 2nd month after
      the surgery. RESULTS: Mean PAP decreased significantly in both groups compared
      with basal levels. The regression was higher in Group II than Group I. Decrease
      in PCWP was more significant in Group II. PAP had decreased similarly in both
      groups according to the postoperative 24th hour echocardiographic evaluation;
      however, at the postoperative second month follow-up, the decrease in PAP was
      more significant in Group II. CONCLUSION: Pulmonary arterial and left atrial
      pressures significantly decreased in the early periods when the stenosis was
      alleviated in the isolated mitral stenosis cases with moderate or high PAP
      levels. This study demonstrates the increased morbidity in patients with higher
      PAP levels undergoing surgery. It seems that moderate PAP levels do not have a
      negative influence on postoperative outcomes.

PMID- 22864320
TI  - Impact of intraoperative transesophageal echocardiography on surgical decisions
      in the cardiovascular operating room.
AB  - OBJECTIVES: To assess the usefulness of intraoperative transesophageal
      echocardiography (IOTEE) in a cardiac surgery department. STUDY DESIGN: Patients
      were examined with IOTEE before and after cardiopulmonary bypass. All studies
      were performed with a Toshiba 270 SSA model imaging device. All IOTEE
      examinations were performed by two cardiovascular surgery residents who are
      experienced in IOTEE. RESULTS: A total of 466 patients (239 men, 227 women) were
      examined by IOTEE from 2001 through 2007. Of these 182 (39%) were performed
      during correction of valvular pathologies, 193 (41%) during coronary operations,
      34 (7%) during combined operations (either valvular or coronary bypass), 8 (1.7%)
      in adult congenital heart operations, 7 (1.5%) in cardiac mass operations, and
      the rest in other miscellaneous operations. TEE examinations performed before and
      after the cardiopulmonary bypass influenced surgical decisions by 14.8% and 9.0%,
      respectively. Decisions regarding the mitral valve were the most frequent
      followed by decisions regarding the tricuspid valve. CONCLUSION: IOTEE
      significantly affected decision making in cardiac surgery operating room. IOTEE
      examination must be a standard procedure for all patients undergoing cardiac
      surgery.

PMID- 22864321
TI  - [Femoral vein guidance for pipe-shaped coronary sinus cannulation and epicardial
      left ventricular lead placement using left subclavian vein approach].
AB  - Variations in coronary sinus (CS) anatomy can make subclavian vein approach
      dif?cult or even impossible for LV lead delivery. A combination of interventional
      and electrophysiological methods is therefore the state of art technique for
      implantation of LV leads. A 52 year-old male patient with ischemic dilated
      cardiomyopathy (LVEF: 15%, QRS: 160 msec) who was symptomatic under optimal
      medical therapy was hospitalized for implantation of cardiac resynchronization
      therapy. Although right ventricular and atrial electrodes were implanted
      successfully, we had difficulty during placement of the left ventricular
      electrode. There was an anatomical variation in CS with a piped shape, which
      prevented cannulation from the superior approach. We describe a practical method
      for guidance of transfemoral route for pipe-shaped CS cannulation and epicardial
      placement of LV lead with superior approach.

PMID- 22864322
TI  - Large pericardial effusion induced by minoxidil.
AB  - A 53-year-old male admitted with increased shortness of breath. In the physical
      examination, he had dyspnea, tachycardia and tachypnea. An echocardiogram showed
      large pericardial effusion (PE) as well as significant pulmonary hypertension. He
      had been started recently on minoxidil for blood pressure control. PE was
      reported to occur with minoxidil treatment both in patients undergoing dialysis
      and those with normal renal function. Pulmonary hypertension has been reported to
      affect the cardiac tamponade physiology. Because of significant pulmonary
      hypertension in our patient, a right heart catheterization was also done, which
      prevented cardiac tamponade. He was treated conservatively without any
      intervention, and PE resolved spontaneously after discontinuation of minoxidil.

PMID- 22864323
TI  - [A sudden rise in INR due to combination of Tribulus terrestris, Avena sativa,
      and Panax ginseng (Clavis Panax)].
AB  - Warfarin sodium is an antithrombin agent used in patients with prosthetic valve
      and atrial fibrillation. However, there are many factors that can change the
      effectiveness of the drug. Today, herbal mixtures promoted through targeted print
      and visual media can lead to sudden activity changes in patients using warfarin.
      In this case report we will present two cases with a sudden rise in INR due to
      using combination of Tribulus terrestris, Avena sativa and Panax ginseng (Panax
      Clavis). Two patients who used warfarin due to a history of aortic valve
      replacement (case 1) and atrial fibrillation (case 2) were admitted to the
      hospital due very high levels of INR detected during routine follow-up. Both
      patients had used an herbal medicine called ''Panax'' during the last month. The
      patients gave no indication regarding a change in diet or the use of another
      agent that might interact with warfarin. In cases where active bleeding could not
      be determinated, we terminated the use of the drug and re-evaluated dosage of
      warfarin before finally discharging the patient.

PMID- 22864324
TI  - [Acute anterior myocardial infarction presented with cardiogenic shock in a
      patient on herbal medication].
AB  - Uncontrolled usage of herbal medications may cause problems that can lead to
      serious complications, including death. Panax is thought to have
      hypocholesterolemic, anticarcinogenic, antiinflammatory, and antimicrobial
      effects via its saponin ingredient and positive inotropic effects via its panax
      ginseng effect. However, clinical studies have shown that it can increase the low
      density lipoprotein (LDL) levels secondary to its hypocholesterolemic effect,
      have a hypertensive effect in chronic users via ginseng abuse syndrome, and also
      have hypotensive effects. Here, we present a case with typical angina pectoris in
      which coronary angiography was suggested but refused. The male patient initiated
      panax therapy and presented to our emergency department with diffuse anterior
      myocardial infarction and cardiogenic shock, and was discharged after appropriate
      therapy.

PMID- 22864325
TI  - [Three case reports of the use of herbal combinations resulted in stent
      thrombosis: herbal combinations; friend or foe?].
AB  - Nowadays, herbal combinations are commonly used in Turkey and around the world.
      In particular, an herbal combination including Tribulus terrestris (TT), Avena
      sativa (AS), and Panax Ginseng (PG), which may be effective in treatment of
      atherosclerosis and thrombosis, is used by patients with coronary artery disease.
      In this paper, we will report three cases with coronary stents who were diagnosed
      with acute coronary syndrome while using this herbal combination of TT, AS and PG
      together with anti-aggregant medications. A 45-year-old man presented with chest
      pain and coronary angiography confirmed a total occluded stent in left anterior
      descending artery which was implanted a year ago. Balloon dialation was performed
      to dilate the stent, resulting in full opening of the vessel. The second case, a
      53-year-old woman, was admitted to the hospital with chest pain. Coronary
      angiography confirmed a total occluded stent, which had been implanted three
      months ago. A balloon was performed to dilate the stent and it was fully opened.
      The third case, a 62-year-old man, presented with chest pain. Coronary
      angiography was performed and there was a 98% stenosis of the circumflex stent,
      which was implanted three months ago. A balloon was performed to dilate the stent
      and it was fully opened. It was learnt that all three patients had used the same
      herbal combination (TT, AS and PG) with dual anti-aggregant therapy for three
      months ago to presentation in the clinic. Patients were discharged with the
      suggestion not to use this herbal combination with dual anti-aggregant therapy.
      There were no problems during the four month follow-up period. Stent thrombosis
      may be caused  by  interactions  between herbal combination (TT, AS and PG) and
      clopidogrel in these patients under dual antiaggregant therapy.

PMID- 22864326
TI  - [Two cases of acute coronary syndrome after intake of Clavis Panax].
AB  - Atherosclerotic cardiovascular disease is an epidemic in today's world. It is one
      of the most common causes of hospitalization and death. Therefore, remedies to
      control or heal the disease are continuously sought. In addition to
      scientifically researched therapies, patients frequently utilize alternative
      medicine. However, effective and toxic doses, metabolisms, and drug interactions
      of the herbs and herbal nutrition supplements are largely unknown. Herein, we
      present two cases with acute coronary syndrome. The first case was admitted with
      a diagnosis of acute inferior myocardial infaction (MI) and a stent was implanted
      to the occluded right coronary artery (RCA). There was a 50% stenosis in his left
      anterior descending artery (LAD). He was admitted with a diagnosis of non-ST
      elevation MI (NSTEMI) 6 months later. In the coronary angiogram, there was stent
      restenosis in RCA, the lesion in LAD had become thrombotic and progressed to a
      stenosis of 90%. He was referred to surgical revascularization. The second case
      was admitted for acute inferior MI and a stent was implanted to the occluded
      circumflex artery. Two months later, he was hospitalized for NSTEMI. Progression
      of coronary plaques to stenosis and stent restenosis was detected and he was
      referred to surgical revascularization. Both patients used the product sold as
      Clavis Panax, which contains panax ginseng, tribulus terrestris, and oat, after
      their first coronary intervention. Intake of a mixture of plant extracts may have
      serious consequences in humans as drug interactions and side effects are unknown.

PMID- 22864327
TI  - [Problems in cardiology specialty training in Turkey].
AB  - Cardiology Specialty Training in our country should be made in accordance with
      the law numbered 1219 on the Practice of Medicine and Related Arts, and according
      to the Medical and Dental Specialist Training Regulation which is published
      according to the 9th article of this law. The duration of Cardiology Specialist
      Training has been defined as 4 years in our country. The European Society of
      Cardiology (ESC), European Union of Medical Specialists (UEMS), and the European
      Cardiology Section Foundation (ECSF) define the duration of Cardiology Specialist
      Training as 6 years. Therefore, insufficient Cardiology residency training occurs
      in our country due to the shortened length of time. In this report, the problems
      of the Cardiology Specialist Training in Turkey will be addressed under different
      headings.

PMID- 22864328
TI  - Case images: a papillary fibroelastoma arising from the tricuspid valve.

PMID- 22864329
TI  - Case images: left ventricular outflow tract to left atrial fistula after aortic
      valve replacement.

PMID- 22864330
TI  - Case images: an 8 French introducer embolized into the patient's femoral vein.

PMID- 22864331
TI  - Case images: bilateral coronary-to-pulmonary artery fistulas.

PMID- 22864332
TI  - Case images: coexistence of discrete subaortic stenosis and unruptured sinus
      Valsalva aneurysm obstructing the right ventricular outflow tract.

PMID- 22864333
TI  - Impact of routine follow-up examinations on life expectancy in ovarian cancer
      patients: a simulation study.
AB  - OBJECTIVE: The clinical benefit of routine follow-up in patients treated for
      ovarian cancer is subject to debate. In this study, the magnitude of the
      potential survival benefit of routine examinations was evaluated by Markov
      modeling. METHODS: The clinical course of ovarian cancer was simulated using a 4
      state nonstationary Markov model. Risk of recurrence and mortality probabilities
      were derived from individual patient data and Statistics Netherlands. The life
      expectancy was simulated for 3 follow-up scenarios: a current, withholding (all
      recurrences detected symptomatically), and perfect follow-up program (all
      recurrences detected asymptomatically). The impact of effective recurrence
      treatment in the future was modeled by varying the mortality ratio between
      patients with asymptomatically versus symptomatically detected recurrences. The
      model was validated using empirical data. RESULTS: The mean life expectancy of
      patients, aged 58 years and in complete clinical remission after primary
      treatment, was 10.8 years. Varying the transition probabilities with +/-25%
      changed the life expectancy by up to 1.1 years. The modeled life expectancy for
      the withholding and perfect follow-up scenarios was also 10.8 years and
      insensitive to model assumptions. In patients with stages IIB to IV, the life
      expectancy was 7.0 years, irrespective of follow-up strategy. A mortality ratio
      of 0.8 for patients with asymptomatically versus symptomatically detected
      recurrences resulted in a gain in life expectancy of 5 months for withholding
      versus perfect follow-up. CONCLUSIONS: Routine follow-up in ovarian cancer
      patients is not expected to improve the life expectancy. The timing of detection
      of recurrent ovarian cancer is immaterial until markedly improved treatment
      options become available.

PMID- 22864334
TI  - Tailoring the treatment of locally advanced squamous cell carcinoma of the vulva:
      neoadjuvant chemotherapy followed by radical surgery: results from a multicenter
      study.
AB  - OBJECTIVE: To determine the feasibility of performing neoadjuvant chemotherapy
      (NCH) followed by radical surgery in patients with locally advanced squamous cell
      carcinoma of the vulva. METHODS: Prospective and multicenter trial. Thirty-five
      patients with a diagnosis of previously untreated locally advanced squamous cell
      carcinoma of the vulva were given 4 schemes of cisplatin-based NCH and 1 NCH
      regimen with single bleomycin. Then, they underwent radical surgery of the vulva
      if clinical response was 50% or more. Age, NCH schemes used, toxicity, response
      to treatment, type of radical surgery performed, and clinical outcome were
      evaluated. RESULTS: Thirty-three patients completed the proposed schemes, and 30
      were assessed for radical surgery. Finally, 27 patients underwent radical surgery
      (radical vulvectomy or radical local excision plus bilateral inguinofemoral
      lymphadenectomy). In 2 cases of persistent rectal involvement, posterior pelvic
      exenteration was performed. Moreover, 24 of 27 patients remain with no evidence
      of disease to date. Toxicity was acceptable. Median age was 62 years (range, 54
      72 years). Median follow-up was 49 months (range, 4-155 months). CONCLUSIONS: The
      use of NCH in selected groups may increase surgical feasibility in initially
      inoperable patients, thus favoring organ preservation and less extensive
      resections. Adverse reactions were acceptable, and vulvoperineal deleterious
      effects that may occur after radiotherapy were consequently avoided.

PMID- 22864335
TI  - Prospective study of sentinel lymph node biopsy without further pelvic
      lymphadenectomy in patients with sentinel lymph node-negative cervical cancer.
AB  - OBJECTIVE: The aim of the present study was to evaluate the incidence of
      lymphedema and cancer recurrence rate in patients with cervical cancer who
      undergo sentinel lymph node (SLN) biopsy alone in the absence of SLN metastases.
      PATIENTS AND METHODS: The study included 35 consecutive patients with cervical
      cancer scheduled for radical hysterectomy at Tohoku University Hospital between
      May 2006 and July 2009. All patients had International Federation of Gynecology
      and Obstetrics stages IA1 to IIA1 disease. Patients in whom SLNs were detected
      unilaterally or not detected and/or whose lymph nodes were diagnosed
      intraoperatively as positive metastasis underwent systemic pelvic
      lymphadenectomy. Patients who were found negative for SLN metastasis did not
      undergo further pelvic lymphadenectomy. RESULTS: The mean number of detected SLNs
      was 4.1 (range, 1-11). True lymph node metastasis could be detected in 11 (31%)
      of the 35 cases. Intraoperative frozen section identified correctly in 8 of 11
      metastatic patients. Twenty-three patients underwent SLN biopsy alone without
      systematic pelvic lymphadenectomy. None of the 23 patients diagnosed with
      negative SLNs have experienced a lymph node recurrence in the pelvic cavity. New
      symptomatic lower extremity lymphedema was identified in 2 (8.7%) of the 23
      patients who underwent SLN biopsy alone and in 5 (42%) of 12 patients who
      underwent systematic lymphadenectomy. CONCLUSION: Radical hysterectomy with SLN
      biopsy alone seems to be a safe and effective strategy for detection of lymph
      node metastasis and for reducing the number of patients with lower extremity
      lymphedema, but a more convenient and sensitive procedure for intraoperative
      diagnosis needs to be established.

PMID- 22864336
TI  - External pelvic and vaginal irradiation versus vaginal irradiation alone as
      postoperative therapy in medium-risk endometrial carcinoma: a prospective,
      randomized study--quality-of-life analysis.
AB  - BACKGROUND: A combination of vaginal brachytherapy and external beam radiotherapy
      was compared with brachytherapy alone in medium-risk endometrial carcinomas.
      Quality-of-life analysis is an important part of a randomized study to find out
      the optimal adjuvant treatment for this group of patients. OBJECTIVE: To evaluate
      the value of adjuvant external beam pelvic radiotherapy in adjunct to vaginal
      brachytherapy in medium-risk endometrial carcinoma. Quality-of-life evaluation is
      the main topic of this report. METHODS: A consecutive series of 527 evaluable
      patients were included in this randomized trial. Median follow-up for patients
      alive was 62 months. The primary study end points were locoregional recurrences
      and overall survival. Secondary end points were recurrence-free survival,
      toxicity, and quality-of-life. European Organization for Research and Treatment
      of Cancer QLQ-C30 and QLQ-OV28 modules were used to evaluate global health
      status, functional scales, and symptom scales. RESULTS: Five-year locoregional
      relapse rates were 1.5% after external beam (ERT) plus vaginal irradiation (VBT)
      and 5% after vaginal irradiation alone (P = 0.013), and 5-year overall survival
      (OS) rates were 89% and 90%, respectively. External beam radiotherapy was
      associated with a higher rate of adverse effects from the intestine and the
      bladder, and quality-of-life parameters deteriorated at the end of radiotherapy
      but recovered to normal levels within a few months. There was a significant
      difference in favor of VBT alone with regard to adverse effects of the bowel and
      urinary tract, and quality-of-life. CONCLUSIONS: Despite a significant
      locoregional control benefit with combined radiotherapy, no survival improvement
      was recorded; but increased late toxicity from the intestine and the bladder.
      External beam irradiation decreased global health status during and after
      treatment, and 3 functional scale items (physical, role, and social). Six of 11
      symptom items showed a pattern favoring vaginal brachytherapy alone.

PMID- 22864337
TI  - Controlling gastric variceal bleeding with endoscopically applied hemostatic
      powder (HemosprayTM).

PMID- 22864339
TI  - Regression of fibrosis: the need for quantitative methods of assessment.

PMID- 22864340
TI  - A quantitative study of intrinsic non-covalent interactions within complexes of
      alpha-cyclodextrin and benzoate derivatives.
AB  - A novel deconvolution method for energy-resolved reaction cross sections is
      applied to determine intrinsic gas-phase dissociation energies for non-covalent
      alpha-cyclodextrin host-guest complexes. M06-2X//M06-L/6-31+G(d,p) calculations
      reproduce the experimental results and enable us to quantify the contribution of
      intermolecular hydrogen bonding.

PMID- 22864341
TI  - Dual fluorophore PNA FIT-probes--extremely responsive and bright hybridization
      probes for the sensitive detection of DNA and RNA.
AB  - Fluorescently labeled oligonucleotides are commonly employed as probes to detect
      specific DNA or RNA sequences in homogeneous solution. Useful probes should
      experience strong increases in fluorescent emission upon hybridization with the
      target. We developed dual labeled peptide nucleic acid probes, which signal the
      presence of complementary DNA or RNA by up to 450-fold enhancements of
      fluorescence intensity. This enabled the very sensitive detection of a DNA target
      (40 pM LOD), which was detectable at less than 0.1% of the beacon concentration.
      In contrast to existing DNA-based molecular beacons, this PNA-based method does
      not require a stem sequence to enforce dye-dye communication. Rather, the method
      relies on the energy transfer between a "smart" thiazole orange (TO) nucleotide,
      which requires formation of the probe-target complex in order to become
      fluorescent, and terminally appended acceptor dyes. To improve upon fluorescence
      responsiveness the energy pathways were dissected. Hydrophobic, spectrally
      mismatched dye combinations allowed significant (99.97%) decreases of background
      emission in the absence of a target. By contrast, spectral overlap between TO
      donor emission and acceptor excitation enabled extremely bright FRET signals.
      This and the large apparent Stokes shift (82 nm) suggests potential applications
      in the detection of specific RNA targets in biogenic matrices without the need of
      sample pre-processing prior to detection.

PMID- 22864342
TI  - [Modern chemistry & multiscale simulations that support current drug design].

PMID- 22864343
TI  - [Analysis of enzymatic reactions by quantum chemical calculations].
AB  - Density functional theory (DFT) is now extensively used as a research tool for
      the investigation of structure and reactivity of biological systems; however, its
      high computational demands still restrict the applicability of DFT to systems of
      a few tens up to one hundred atoms. A combined quantum mechanical/molecular
      mechanical (QM/MM) approach is applicable as an important method to study whole
      enzyme systems more than ten thousands atoms. We have investigated methane
      monooxygenase, dopamenie beta-monooxygenase, tyrosinase, B12 dependent diol
      dehydratase, etc. using DFT and QM/MM calculations. In particular, we have done
      some computational mutation analyses about the amino acid residues at the active
      site of diol dehydratase. Our DFT and QM/MM calculations can correctly describe
      the structures and activation barriers of intermediates and transition states in
      the protein environment, and therefore, we successfully revealed the catalytic
      role of amino acid residues at the active site of diol dehydratase. Predicted
      relative activities of mutants are consistent with experimentally observed
      reaction rates. These results encourage us to apply QM/MM research to enzymatic
      reactions, functional analysis of active-site residues, and rational design of
      enzymes with new catalytic functions.

PMID- 22864344
TI  - [Non-commutative geometrical drug discovery--the principle of geometrical
      regulation].
AB  - We developed a theoretical framework for the regulation of biological
      macromolecules using the logically designed compounds. According to the
      cohomology theory, algebraic objects can be translated into geometrical ones.
      Successfully established quantum theory at 20th century, which essentially deals
      with the non-commutative nature of the space, also suggests the non-commutative
      topology of biological space. Arithmetic geometrical representation of the
      molecules as well as the macroscopic membranous structures would uncover their
      structural groups in Hilbert space. In order to construct the concrete image of
      biological space, here we combined quantum chemical (QC) model, all-atom (AA)
      model and coarse grained (CG) model, into one program designated 'NAGARA'. These
      three models can be arranged in an arbitrary manner to yield the desired
      statistical ensemble. For example, QC model was applied to the optimization of
      the chemical structure of anti-prion lead compound GN8. Arithmetic geometrical
      representation of these algebraic models is in progress.

PMID- 22864345
TI  - [Structure-activity relationship of novel vitamin K analogues as steroid and
      xenobiotic receptor (SXR) agonists].
AB  - Vitamin K2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor
      (SXR), that induces the gene expressions of CYP3A4. We synthesized new vitamin K
      analogues with the same isoprene side chains symmetrically introduced at the 2
      and 3 positions of 1,4-naphthoquinone and vitamin K2 analogues with hydroxyl or
      phenyl groups at the omega-terminal of the side chain. The upregulation of SXR
      mediated transcription of the target gene by the analogues was dependent on the
      length of the side chain and the hydrophobicity of the omega-terminal residues.
      Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.

PMID- 22864346
TI  - [New sesquiterpenoids from the rhizomes of Petasites japonicus MAXIM. and the
      roots of Ligularia dentata HARA].
AB  - Over the past twenty years, our research group has been involved in the
      phytochemical study of terpenoids from Compositae plants. From seven species,
      namely, Erigeron annuus (L.) PERS., Erigeron philadelphicus L., Erigeron
      sumatrensis RETZ., Ligularia dentata HARA, Ligularia stenocephala MATSUM. et
      KOIDZ., Petasites japonicus MAXIM., and Tussilago farfara L., we isolated 83 new
      compounds. In this review, structural features of 19 eremophilane-type
      sesquiterpenoids from rhizomes of P. japonicus and 9 bisabolane-type
      sesquiterpenoids from roots of L. dentata are discussed.

PMID- 22864347
TI  - [The regulation of ganglioside GM3 synthesis].
AB  - Glycosphingolipids (GSLs) exist in the outer leaflet of the plasma membrane,
      where they form lipid microdomains that function as platforms for the regulation
      of trans-membrane signal transduction. In mammals, complex GSLs differing in the
      number and/or type of sugar species are produced in a cell-type specific manner,
      and the variety of glycan structures in GSLs are believed to determine specific
      cell functions. The glycan moieties of GSLs are synthesized at the luminal side
      of the Golgi apparatus by multiple Golgi-resident glycosyltransferases. Since the
      expression levels of most endogenous glycosyltransferases are relatively low,
      their detection is generally difficult. Nevertheless, we have succeeded in
      detecting endogenous mouse GM3 synthase (GM3S), the primary glycosyltransferase
      responsible for the biosynthesis of ganglio-series gangliosides. Mouse GM3S
      (mGM3S) has three isoforms (M1-GM3S, M2-GM3S, and M3-GM3S), each with a distinct
      length in its NH2-terminal cytoplasmic tail. These isoforms are produced by leaky
      scanning from two mRNA variants, mGM3Sa and mGM3Sb. M1-GM3S is stably localized
      in the endoplasmic reticulum (ER), as a result of retrograde transport signals
      (arginine [R]-based motifs); consequently, its in vivo GM3 synthesis activity is
      very low compared with that of other isoforms. In contrast, both M2-GM3S and M3
      GM3S are localized in the Golgi apparatus, yet each exhibits a distinct
      intracellular fate. M2-GM3S is rapidly degraded in the lysosomes, whereas M3-GM3S
      is retained in the Golgi apparatus. A system that produces GM3S isoforms having
      such distinct characteristics is likely to be of critical importance in the
      regulation of GM3 biosynthesis under various pathological and physiological
      conditions.

PMID- 22864348
TI  - [Retinoids as promising treatment for non-alcoholic fatty liver disease].
AB  - Non-alcoholic fatty liver disease (NAFLD) is frequently associated with insulin
      resistance, suggesting its crucial role in the development and progression of
      NAFLD. We used a mouse model of high-fat, high-fructose (HFHFr) diet-induced
      NAFLD to examine the effects of retinoids on insulin resistance. Dietary
      administration of all-trans-retinoic acid (ATRA) significantly improved insulin
      sensitivity in C57BL/6J mice fed the HFHFr diet, and in KK-Ay mice but not in the
      leptin-deficient ob/ob mice. ATRA treatment significantly upregulated hepatic
      leptin receptor (LEPR) expression. In agreement with these observations, in vitro
      experiments showed ATRA directly induced LEPR gene expression through RARalpha.
      In the livers of C57BL/6J mice administered ATRA, insulin receptor substrate-1
      (IRS1) was activated concomitantly with the phosphorylation of Janus kinase-2 and
      signal transducer and activator of transcription-3 (STAT3). STAT3 phosphorylation
      was also observed in KK-Ay but not in ob/ob mice. In in vitro experiments, ATRA
      significantly enhanced insulin-induced IRS1 tyrosine phosphorylation solely in
      the presence of leptin. A selective RARalpha/beta agonist, tamibarotene, also
      enhanced hepatic LEPR expression, STAT3 phosphorylation, and ameliorated insulin
      resistance in KK-Ay mice. We discovered an unrecognized mechanism of retinoid
      action for the activation of hepatic leptin signaling, which resulted in
      enhancing insulin sensitivity in two mouse models of insulin resistance.
      Moreover, we also found that retinoids attenuate hepatic iron overload and iron
      induced oxidative stress, which have recently emerged as an important factor for
      the development and progression of insulin resistance. Our data suggest that
      retinoids might have potential for treating NAFLD associated with insulin
      resistance.

PMID- 22864349
TI  - [Dynamic analysis of pharmacokinetics of orally administered drugs using positron
      emission tomography].
AB  - Positron emission tomography (PET) is a powerful and noninvasive technology for
      molecular imaging in living systems. Its high sensitivity and high spatial
      temporal resolution make this technology particularly useful to analyze the
      disposition of drugs in the body. PET technology could be applied to analyze the
      process of distribution of orally administered drugs on the basis of time
      profiles of radioactivity in vivo. Kinetic analysis of radioactivity derived from
      18F-labeled 2-fluoro-2-deoxy-D-glucose administered orally to rats under several
      conditions indicated that not only gastric emptying and intestinal transit but
      also the rate constant of intestinal absorption and limited process of oral
      absorption could be evaluated quantitatively. After oral administration of 11C
      labeled telmisartan with or without non-radiolabeled telmisartan, systemic
      bioavailability and hepatic distribution of radioactivity significantly increased
      non-linearly with dose. In the intestinal lumen, telmisartan and its glucuronide,
      converted by UDP-glucuronosyl transferase (UGT), were detected and the ratio of
      telmisartan decreased at a high dose of telmisartan. In vitro permeation study
      revealed that telmisartan is a substrate of P-glycoprotein (P-gp). It was
      reported that hepatic uptake of telmisartan is mediated by organic anion
      transporting polypeptide 1B3 (OATP1B3) and most of the hepatic radioactivity in
      the liver is derived from telmisartan. These results indicated that P-gp for
      intestinal absorption, OATP1B3 for hepatic uptake and UGT for glucuronidation
      could be considered as limiting steps of orally administered telmisartan.
      Therefore, PET study is highly anticipated to be a potent tool for better
      understanding of gastrointestinal absorption and the subsequent tissue
      distribution of various drugs and candidates.

PMID- 22864350
TI  - [Identification and characterization of the outermost layer of Bacillus subtilis
      spores].
AB  - The Gram-positive bacterium Bacillus subtilis forms spores when conditions are
      unsuitable for growth. The spores are encased in a multilayered shell that
      includes a cortex and a spore coat, and remain viable for long periods in the
      harsh environment. In the present article, recent progress in our understanding
      of the outer structure of B. subtilis spores is reviewed in the Japanese
      language. Although spore coat assembly involves the deposition of at least 70
      distinct protein species, the positions of most of such proteins have not been
      experimentally determined. To this end, the diameters of the protein layers and
      spores were measured using fluorescence microscopy and then the positions of
      proteins in the spore coat of B. subtilis spores were estimated. The locations of
      16 proteins were determined using this method. One protein was assigned to the
      cortex, nine to the inner coat, and four to the outer coat. Further, two
      proteins, CgeA and CotZ, were assigned to a previously unidentified outermost
      layer. McKenney et al. have also identified the outermost layer using a similar
      method; the layer was termed the "crust". Immunofluorescence microscopy revealed
      that the crust is indeed the most external layer of B. subtilis spores.
      Mutational analysis indicated that all genes in the cotVWXYZ cluster were
      involved in spore crust synthesis and that CotY and CotZ played critical roles in
      crust formation.

PMID- 22864351
TI  - [Study of stereochemical structures of complex of tea catechins and caffeine].
AB  - Two crystals of a complex of (-)-gallocatechin-3-O-gallate (GCg) with caffeine
      and crystals of the complexes of (+)-catechin (CA) and (-)-catechin-3-O-gallate
      (Cg) with caffeine were prepared, and their stereochemical structures and
      intermolecular interactions were determined in X-ray crystallographic analysis.
      GCg formed 1:2 and 2:2 complexes with caffeine, and pi-pi interactions formed
      between the aromatic rings of GCg and caffeine in both complexes. In addition, CA
      of nongalloylated catechins formed a 1:1 complex with caffeine through
      intermolecular hydrogen bonds, whereas Cg of galloylated catechins formed a 1:2
      complex with caffeine, which was formed by face-to-face and offset pi-pi
      interactions and intermolecular hydrogen bonds.

PMID- 22864352
TI  - [Effect of flavin adenine dinucleotide on ultraviolet B induced damage in
      cultured human corneal epithelial cells].
AB  - This study evaluated the effects of flavin adenine dinucleotide (FAD) on
      ultraviolet B (UV-B)-induced damage in cultured human corneal epithelial (HCE-T)
      cells. The cultured HCE-T cells were treated with 0.003125-0.05% FAD before
      exposure to 80 mJ/cm2 UV-B. Cell viability was measured 24 h after UV-B
      irradiation using the MTS assay. Reactive oxygen species (ROS) were detected 30
      min after UV-B irradiation using 5-(and-6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate acetyl ester. Apoptosis was evaluated 4 h
      after UV-B irradiation in the caspase-3/7 activity assay. UV-B irradiation
      reduced cell viability and stimulated ROS production and caspase-3/7 activity in
      HCE-T cells. Pretreatment of UV-B irradiated HCE-T cells with FAD significantly
      attenuated cell viability reduction and inhibited the stimulation of both ROS
      production and caspase-3/7 activity due to UV-B exposure compared with those with
      vehicle (0% FAD). These results clarified that FAD inhibits ROS-mediated
      apoptosis by UV-B irradiation in HCE-T cells and suggest that FAD may be
      effective as a radical scavenger in UV-B-induced corneal damage.

PMID- 22864353
TI  - [Equivalence studies of pravastatin original and generic drugs by dissolution
      test].
AB  - There are various opinions regarding the different functions of original and
      generic drugs. We used the paddle method to perform dissolution tests on
      pravastatin sodium tablets (10 mg) to investigate the causes for these
      differences. We used water and buffer solutions adjusted to pH 1.2 (JP1) and pH
      6.8 (JP2), which are described in the Japanese Pharmacopoeia. The pravastatin
      concentration was measured by UV spectroscopy and HPLC. There were significant
      differences in the percentages dissolved of original and generic drugs after 5
      and 10 min. On the other hand, the dissolution behaviors using water and JP2
      measured by HPLC were similar to the results obtained by UV spectroscopy.
      However, the percentage dissolved of pravastatin using JP1 decreased with time
      because pravastatin degraded in JP1. There were also significant differences in
      the pravastatin concentrations of the original and generic drugs at 5, 15, 30,
      and 45 min. Based on the above results, since the original drug has a slower
      dissolution rate than the generic drugs, it is necessary to be cautious about the
      degradation of pravastatin in the stomach and the bioavailability of pravastatin
      due to the different dissolution rates and the different residual amount of
      pravastatin in the stomach.

PMID- 22864354
TI  - [A research of letter color visibility in package insert information using
      simulator].
AB  - Package insert of pharmaceutical drug is one of the most prioritized information
      for pharmacists to secure safety of patients. However, the color of character,
      size, font and so on are various company by company product to product from a
      viewpoint of visibility. It may be cause a serious accident in case visibility is
      unclear, although it is the most important information. Moreover, package insert
      with high visibility is required for color vision defectives from a viewpoint of
      a universal design. Then, the authors selected the package insert which has the
      boxed warning in the ethical pharmaceutical currently stored mostly in the
      present health insurance pharmacy and quantified the red color using the color
      meter. We advocate the state of a suitable package insert from a viewpoint of a
      universal design, whether the red color is high visible or not for color vision
      defectives using simulator.

PMID- 22864355
TI  - [Photometric determination of Cu2+ ion using octabromo-tetrakis(4
      methylpyridyl)porphine].
AB  - Octabromo-tetrakis(4-methylpyridyl)porphine (OBTMPyP), an octabromonated compound
      with 4 pyrole rings of tetrakis(4-methylpyridyl)porphine, selectively forms a
      complex with Cu2+ ions at pH 2.0. When 3.6*10(-5) mol/L OBTMPyP was added to the
      reaction mixture, the calibration curve showed good linearity for Cu2+ ions
      ranging from 0.01-2.2 ug (addition of 1.0 mL). A good coefficient of variation
      (Cu2+ ions=1.5 ug (addition of 1.0 mL), n=10, 0.8%) was obtained. The molar
      absorption coefficient (epsilon) based on Cu2+ ions was 8.5*10(4) L/mol*cm. This
      value was 6-fold greater than that determined with a clinical chemical analysis
      kit using the bathocuproine sulfonic acid method, which is a well-known method
      for spectrophotometric determination of the Cu2+ ion concentration. A
      deproteination method was successfully applied in the clinical analysis kit for
      determination of Cu2+ ion concentrations in control serum I, and the values
      determined using this method and the bathocuproine sulfonic acid method were
      almost the same.

PMID- 22864356
TI  - [Migration of eight harmful elements from metal accessories that infants may
      swallow by mistake].
AB  - The International Standard ISO 8124-3:2010 "Safety of toys--Part 3: Migration of
      certain elements" controls the levels of migrated eight harmful elements
      (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) from
      infants toys. Moreover, the Japanese Food Sanitation Law controls the levels of
      migrated lead from metal accessory toys. However, the levels of migrated harmful
      elements from metal accessories that are not infants toys are not controlled,
      since they are not covered by the ISO Standard or the Food Sanitation Law.
      Therefore, we investigated the level of eight harmful elements migrated from
      metal accessories that infants may swallow by mistake. The extraction test of ISO
      8124-3:2010 was executed in 117 products (total 184 specimens), and the
      concentration of these eight elements was measured by inductively coupled plasma
      mass spectroscopy (ICP-MS). As a result, 28 and one products released lead and
      cadmium beyond the maximum acceptable levels of the ISO standard, respectively.
      Metal accessories that infants may swallow by mistake should ideally not release
      harmful elements such as lead and cadmium.

PMID- 22864357
TI  - Reactive oxygen species induced by presynaptic glutamate receptor activation is
      involved in [(3)H]GABA release from rat brain cortical nerve terminals.
AB  - We investigated the production of reactive oxygen species (ROS) as a response to
      presynaptic glutamate receptor activation, and the role of ROS in
      neurotransmitter (GABA) release. Experiments were performed with rat brain
      cortical synaptosomes using glutamate, NMDA and kainate as agonists of glutamate
      receptors. ROS production was evaluated with the fluorogenic compound
      dichlorodihydrofluorescein diacetate (H(2)DCF-DA), and GABA release was studied
      using synaptosomes loaded with [(3)H]GABA. All agonists were found to stimulate
      ROS production, and specific antagonists of NMDA and kainate/AMPA receptors,
      dizocilpine hydrogen maleate (MK-801) and 6-cyano-7-nitroquinoxaline-2,3-done
      (CNQX), significantly inhibited the ROS increase. Spontaneous as well as agonist
      evoked ROS production was effectively attenuated by diphenyleneiodonium (DPI), a
      commonly used potent inhibitor of NADPH oxidase activity, that suggests a high
      contribution of NADPH-oxidase to this process. The replacement of glucose with
      pyruvate or the simultaneous presence of both substrates in the medium led to the
      decrease in spontaneous and NMDA-evoked ROS production, but to the increase in
      ROS production induced by kainate. Scavenging of agonist-evoked ROS production by
      a potent antioxidant N-acetylcysteine was tightly correlated with the inhibition
      of agonist-evoked GABA release. Together, these findings show that the activation
      of presynaptic glutamate receptors induces an increase in ROS production, and
      there is a tight correlation between ROS production and GABA secretion. The
      pivotal role of kainate/AMPA receptors in ROS production is under discussion.

PMID- 22864358
TI  - miR-433 is aberrantly expressed in myeloproliferative neoplasms and suppresses
      hematopoietic cell growth and differentiation.
AB  - BCR-ABL-negative myeloproliferative neoplasms (MPNs) are most frequently
      characterized by the JAK2V617F gain-of-function mutation, but several studies
      showed that JAK2V617F may not be the initiating event in MPN development, and
      recent publications indicate that additional alterations such as chromatin
      modification and microRNA (miRNA) deregulation may have an important role in MPN
      pathogenesis. Here we report that 61 miRNAs were significantly deregulated in
      CD34+ cells from MPN patients compared with controls (P<0.01). Global miRNA
      analysis also revealed that polycythemia vera (JAKV617F) and essential
      thrombocythemia (JAK2 wild type) patients have significantly different miRNA
      expression profiles from each other. Among the deregulated miRNAs, expression of
      miR-134, -214 and -433 was not affected by changes in JAK2 activity, suggesting
      that additional signaling pathways are responsible for the deregulation of these
      miRNAs in MPN. Despite its upregulation in MPN CD34+ and during normal
      erythropoiesis, both overexpression and knockdown studies suggest that miR-433
      negatively regulates CD34+ proliferation and differentiation ex vivo. Its novel
      target GBP2 is downregulated during normal erythropoiesis and regulates
      proliferation and erythroid differentiation in TF-1 cells, indicating that miR
      433 negatively regulates hematopoietic cell proliferation and erythropoiesis by
      directly targeting GBP2.

PMID- 22864359
TI  - PICking apart Pol II initiation.

PMID- 22864360
TI  - Writers and readers: deconvoluting the harmonic complexity of the histone code.

PMID- 22864361
TI  - Replication origins run (ultra) deep.

PMID- 22864365
TI  - Elastomer based tunable optofluidic devices.
AB  - The synergetic integration of photonics and microfluidics has enabled a wide
      range of optofluidic devices that can be tuned based on various physical
      mechanisms. One such tuning mechanism can be realized based on the elasticity of
      polydimethylsiloxane (PDMS). The mechanical tuning of these optofluidic devices
      was achieved by modifying the geometry of the device upon applying internal or
      external forces. External or internal forces can deform the elastomeric
      components that in turn can alter the optical properties of the device or
      directly induce flow. In this review, we discuss recent progress in tunable
      optofluidic devices, where tunability is enabled by the elasticity of the
      construction material. Different subtypes of such tuning methods will be
      summarized, namely tuning based on bulk or membrane deformations, and pneumatic
      actuation.

PMID- 22864366
TI  - Automatic localization of vertebral levels in x-ray fluoroscopy using 3D-2D
      registration: a tool to reduce wrong-site surgery.
AB  - Surgical targeting of the incorrect vertebral level (wrong-level surgery) is
      among the more common wrong-site surgical errors, attributed primarily to the
      lack of uniquely identifiable radiographic landmarks in the mid-thoracic spine.
      The conventional localization method involves manual counting of vertebral bodies
      under fluoroscopy, is prone to human error and carries additional time and dose.
      We propose an image registration and visualization system (referred to as
      LevelCheck), for decision support in spine surgery by automatically labeling
      vertebral levels in fluoroscopy using a GPU-accelerated, intensity-based 3D-2D
      (namely CT-to-fluoroscopy) registration. A gradient information (GI) similarity
      metric and a CMA-ES optimizer were chosen due to their robustness and inherent
      suitability for parallelization. Simulation studies involved ten patient CT
      datasets from which 50 000 simulated fluoroscopic images were generated from C
      arm poses selected to approximate the C-arm operator and positioning variability.
      Physical experiments used an anthropomorphic chest phantom imaged under real
      fluoroscopy. The registration accuracy was evaluated as the mean projection
      distance (mPD) between the estimated and true center of vertebral levels. Trials
      were defined as successful if the estimated position was within the projection of
      the vertebral body (namely mPD <5 mm). Simulation studies showed a success rate
      of 99.998% (1 failure in 50 000 trials) and computation time of 4.7 s on a
      midrange GPU. Analysis of failure modes identified cases of false local optima in
      the search space arising from longitudinal periodicity in vertebral structures.
      Physical experiments demonstrated the robustness of the algorithm against quantum
      noise and x-ray scatter. The ability to automatically localize target anatomy in
      fluoroscopy in near-real-time could be valuable in reducing the occurrence of
      wrong-site surgery while helping to reduce radiation exposure. The method is
      applicable beyond the specific case of vertebral labeling, since any structure
      defined in pre-operative (or intra-operative) CT or cone-beam CT can be
      automatically registered to the fluoroscopic scene.

PMID- 22864367
TI  - Author response: is drusen area really so important?

PMID- 22864368
TI  - Evidence-based design: medical and design researcher collaboration.

PMID- 22864369
TI  - Evidence-based design: part of evidence-based medicine?

PMID- 22864370
TI  - Tranexamic acid reduces blood transfusion in surgical patients while its effects
      on thromboembolic events and mortality are uncertain.

PMID- 22864371
TI  - Thrombolytic therapy with or without a vena cava filter results in a lower case
      fatality rate in unstable patients with acute pulmonary embolism.

PMID- 22864372
TI  - How to confidently teach EBM on foot: development and evaluation of a web-based e
      learning course.
AB  - BACKGROUND: Scarcity of well-trained clinical tutors is a key constraint in
      integrating teaching of evidence-based medicine (EBM) into clinical activities.
      OBJECTIVES: We developed a web-based educational course for clinical trainers to
      confidently teach EBM principles in everyday practice. Its e-learning modules
      defined the learning objectives and incorporated video clips of practical and
      effective EBM teaching methods for exploiting educational opportunities in six
      different clinical settings. METHODS: We evaluated the course with clinical
      tutors in different specialties across six European countries using a
      questionnaire to capture learning achievement against preset objectives. RESULTS:
      Among 56 tutors, 47 participants (84%) improved their scores from baseline. The
      mean pre-course score was 69.2 (SD=10.4), which increased to 77.3 (SD=11.7)
      postcourse (p<0.0001). The effect size was moderate with a Cohen's d of 0.73.
      CONCLUSIONS: An e-learning approach incorporating videos of applied EBM teaching
      and learning based on real clinical scenarios in the workplace can be useful in
      facilitating EBM teaching on foot. It can be integrated in the continuing
      professional development programmes for clinical trainers.

PMID- 22864373
TI  - What effect does breastfeeding have on coeliac disease? A systematic review
      update.
AB  - OBJECTIVE: To update the evidence published in a previous systematic review and
      meta-analysis that compared the effect of breastfeeding on risk of coeliac
      disease (CD). MATERIAL AND METHODS: A systematic review of observational studies
      published between 1966 and May 2004 on the subject was conducted in 2005. This
      update is a systematic review of observational studies published between June
      2004 and April 2011. Pubmed, EMBASE and Cinahl were searched for published
      studies that examined the association between breastfeeding and CD. RESULTS:
      After duplicates were removed 90 citations were screened. Four observational
      studies were included in the review. Two of three studies which had examined the
      duration of breastfeeding and CD reported significant associations between longer
      duration of breastfeeding and later onset of CD (OR ranged from 0.18 to 0.665).
      Breastfeeding during the introduction of gluten to the infant was reported to
      have a protective effect in two studies. CONCLUSIONS: Our findings support
      previous published findings that breastfeeding seems to offer a protection
      against the development of CD in predisposed infants. Breastfeeding at time of
      gluten introduction is the most significant variable in reducing the risk. Timing
      of gluten introduction may also be a factor in the development of CD.

PMID- 22864374
TI  - The osmolality of nonionic, iodinated contrast agents as an important factor for
      renal safety.
AB  - OBJECTIVE: Nonionic iodinated contrast agents (CAs) can be divided into
      monomeric, low-osmolar, and dimeric, iso-osmolar classes. In clinical practice,
      renal tolerance of CAs is a concern, especially in patients with impaired renal
      function. With regard to renal safety, we wanted to evaluate the role of
      osmolality and viscosity in renal tolerance. MATERIAL AND METHODS: We generated a
      formulation (iodixanol/mannitol) consisting of the dimeric iodixanol with an
      osmolality of the monomeric iopromide. Male Han-Wistar rats were intravenously
      injected with low-osmolar iopromide 300, iso-osmolar iodixanol 320, and
      iodixanol/mannitol. Saline and diatrizoate were used as controls. A total number
      of 227 rats were used in the following experiments. We compared the impact of
      osmolality on renal iodine retention using computed tomography 2 and 24 hours
      postinjection (p.i.). The animals were killed 2, 24, and 72 hours after
      injection, and the kidneys were excised for further investigations. Changes in
      renal cell proliferation were analyzed by 5-bromo-2'-deoxyuridine incorporation
      48 hours p.i. as a degree of tissue regeneration after induced injury. To specify
      potential renal injury, we quantified the expression of acute kidney injury (AKI)
      markers (kidney injury marker-1 [KIM-1], neutrophil gelatinase-associated
      lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) by quantitative
      real-time polymerase chain reaction. Furthermore, the kidneys were analyzed
      histologically, including immunofluorescence analysis. RESULTS: After intravenous
      application of the CAs into Han-Wistar rats, renal iodine concentration was
      increased (3-fold) for iodixanol 2 hours p.i. and iodine retention was detected
      to be prolonged 24 hours p.i. compared with iopromide injection (iodixanol, 520
      +/- 50 Hounsfield Units [HU] vs iopromide, 42 +/- 5 HU). The higher iodine
      concentration 2 hours p.i. upon iodixanol injection was reduced almost to the
      level of iopromide when injecting iodixanol/mannitol (iopromide: 289 +/- 68 HU vs
      iodixanol/mannitol: 343 +/- 68 HU). In addition, iodixanol application induced
      increased renal cell proliferation (2.7-fold vs saline), indicating renal injury,
      which was significantly lower in iopromide-treated animals (1.6-fold vs saline).
      More detailed analysis of markers for AKI revealed that iodixanol significantly
      induced the expression of PAI-1 (7.7-fold at 2 hours) as well as KIM-1 (2.1-fold)
      and NGAL (3.2-fold) at 2 and 24 hours when compared with saline treatment. In
      contrast, the expression of markers for AKI was low after iopromide (1.4-fold
      NGAL, 1.7-fold PAI-1, KIM-1 not significant) and iodixanol/mannitol (1.6-fold
      NGAL, 2.6-fold PAI-1, KIM-1 not significant) injection. CONCLUSION: The present
      results clearly show that prolonged iodine retention and the enhanced expression
      of kidney injury markers are caused mainly by the explicitly higher urine
      viscosity induced by iodixanol. We conclude that the osmolality of low-osmolar
      CAs such as iopromide induces a positive diuretic effect that is responsible for
      rapid iodine clearance and prevents increased expression of acute injury markers
      in the kidney.

PMID- 22864375
TI  - Comparison of two different iron oxide-based contrast agents for discrimination
      of benign and malignant lymph nodes.
AB  - OBJECTIVES: The aim of this study was to investigate the performance of 2
      different ultrasmall superparamagnetic iron oxide particles-based contrast agents
      for intravascular magnetic resonance lymphography in normal, inflammatory, and
      tumor-bearing lymph nodes in rabbits. MATERIALS AND METHODS: Two USPIO agents
      were assessed: Sinerem and P904 (both Guerbet Research, Aulnay-sous-Bois,
      France). Signal change of popliteal and paraaortic lymph nodes were studied in VX
      2 tumor-bearing rabbits (n = 4) and rabbits in whom complete Freund adjuvant had
      been applied (n = 6). Image acquisition was performed before and 5 to 120 minutes
      and 24 hours after bolus injection of Sinerem (n = 5) and P904 (n = 5). Lymph
      node size was assessed and signal-to-noise ratios of lymph nodes were calculated.
      The contrast agents were compared regarding nodal signal changes over time.
      Furthermore, sensitivities, specificities, and negative and positive predictive
      values were calculated for both contrast agents, with histopathology serving as
      the standard of reference. RESULTS: No statistically significant size differences
      were detected between normal, reactively enlarged and tumor-infiltrated lymph
      nodes. Signal change over time showed greater differences between benign and
      metastatic lymph nodes for P904 especially at 24 hours after injection, whereas
      Sinerem showed the highest signal loss in benign nodes. After 24 hours, P904
      showed a higher sensitivity (0.75 vs 0.67) and higher specificity (1 vs 0.94)
      compared with Sinerem. At earlier time points, sensitivity for Sinerem was lower
      (0.33), whereas for P904, sensitivity at 120 minutes was as good as after 24
      hours (0.75). CONCLUSION: Magnetic resonance lymphography with USPIO contrast
      agents allows for differentiation of reactively enlarged lymph nodes compared
      with metastatic nodes. P904 yielded higher sensitivity and specificity values,
      with higher signal differences between benign and malignant enlarged lymph nodes.
      Furthermore, diagnosis seems to be possible earlier. This agent therefore seems
      to be a promising tool for staging cancer patient.

PMID- 22864376
TI  - Gradient shimming during magnetic resonance imaging of the liver: comparison of a
      standard protocol versus a novel reduced protocol.
AB  - PURPOSE: The aim of this study was to examine the effect of minimizing prescan
      adjustments on table time and image quality in magnetic resonance imaging (MRI)
      of the liver. MATERIALS AND METHODS: This prospective Health Insurance
      Portability and Accountability Act-compliant study was approved by the
      institutional review board, and written informed consent was obtained. Ten
      volunteers were imaged twice using a noncontrast liver MRI protocol consisting of
      a total of 10 pulse sequences, once with a standard protocol and once with a
      fixed table position/minimized prescan adjustment protocol (in random order).
      Total examination time was evaluated according to a Lean Six Sigma framework.
      Quantitative sequences, including diffusion-weighted imaging with apparent
      diffusion coefficient, multi-echo Dixon fat percentage, and the transverse
      relaxation time, were evaluated and compared between the two protocols. Two
      experienced readers, blinded to the protocol used, compared image quality between
      the two protocols. RESULTS: The average number of prescan adjustment steps per
      examination was reduced from 58.0 to 22.1 using the minimal shimming protocol
      compared with the normal shimming protocol (P < 0.001). Mean business value added
      time (scan preparatory time) was reduced by 58% (3 minutes 3 seconds vs 7 minutes
      13 seconds), whereas mean total examination time was 20% lower (18 minutes 13
      seconds vs 22 minutes 48 seconds, P < 0.001). Quantitative measures obtained
      using the two protocols were equivalent, and neither reader detected a
      significant difference in subjective image quality. CONCLUSION: Fixing table
      position minimizes prescan adjustments and reduces total table time in liver MRI
      without adversely affecting image quality.

PMID- 22864377
TI  - Dose-wise scanning in visceral computed tomography angiography: a phantom study.
AB  - OBJECTIVES: The aim of this study was to analyze the influence of the tube
      current-time product in multidetector computed tomography angiography on the
      accuracy of stenosis quantification in a phantom model of occlusive vessel
      disease. MATERIALS AND METHODS: Stenosed pelvic and visceral arteries were
      simulated using acrylic tubes (inner diameter: small, 4.0 mm; large, 6.5 mm)
      filled with plaque material (epoxy resin, hydroxylapatite, glass bubbles) to
      create different degrees of stenosis and plaque composition (calcified plaques,
      >1000 Hounsfield units [HU]; soft plaques, ~50 HU; inhomogeneous plaques, 50-1000
      HU). The lumen was filled with water-diluted contrast material (Iomeprol 400;
      Bracco Imaging, Konstanz, Germany) to increase the density to 350 HU. The vessel
      phantoms were inserted in an Alderson phantom and imaging was conducted on a 64
      slice MDCT (Somatom Definition, Siemens, Forchheim, Germany; collimation, 0.6 mm;
      reconstructed slice thickness, 1 mm; 120 kVp) using 8 different image acquisition
      protocols (IAPs), with reference tube current-time products (IQualRef) ranging
      between 20 and 280 mAs (IAP20-IAP280). The signal-to-noise ratio was calculated
      for each IAP. The measured luminal area within a stenosis was correlated to the
      known value using the Kappa-Lin test (kappaLin). A decrease of 10% of the maximum
      achievable correlation was defined as substantial. The sensitivity and
      specificity of hemodynamically relevant stenoses (>50%) were computed. For all
      IAPs, the effective dose was measured with thermoluminescence dosimetry and
      calculated with CTEXPO 2.0 (ICRP103). RESULTS: The measured effective dose ranged
      from 0.8 to 10.7 mSv. The calculated effective dose was approximately 10% lower
      for each IAP (0.7-9.8 mSv). A total of 2592 stenosis measurements were performed.
      In large vessels, the correlation was almost perfect for IAP80 to IAP280
      (kappaLin = 0.91-0.95). In comparison, overall correlation was inferior in small
      vessels and was substantial for IAP280 to IAP120 (kappaLin = 0.89-0.82). Overall,
      the best correlation was observed in calcified (kappaLin = 0.95) and soft
      (kappaLin = 0.93) plaques as compared with inhomogeneous (kappaLin = 0.89)
      plaques. A substantial decrease in the correlation was observed below IAP100 for
      the large vessel phantoms and IAP120 for the small vessel phantoms. The
      sensitivity of hemodynamically relevant stenoses was 90% to 99% for IAP20 to
      IAP280 and both vessel diameters, whereas the specificity decreased from 91%
      (IAP280) to 31% (IAP20) for the large vessel phantoms and from 81% to 25%,
      respectively, for the smaller vessel phantoms. CONCLUSION: In large (>6.5 mm)
      vessel phantoms that simulate pelvic and renal arteries, representing a high
      contrast scenario, a substantial dose reduction is feasible as compared with
      established abdominal imaging protocols. In smaller vessel phantoms that
      represent intestinal arteries, the quality of luminal delineation is already
      limited because of the spatial resolution. Therefore, an increase in image noise
      can only be accepted to a smaller degree and the potential dose reduction is
      limited but still substantial.

PMID- 22864378
TI  - Anti-inflammatory drug evaluation in ApoE-/- mice by ultrasmall superparamagnetic
      iron oxide-enhanced magnetic resonance imaging.
AB  - OBJECTIVES: The renin-angiotensin system and local phagocytic activity play a
      major role in atherosclerotic plaque development. Treatment with irbesartan, an
      antagonist of angiotensin II receptor, can decrease atherosclerotic lesion
      formation. Iron oxide-enhanced magnetic resonance imaging (MRI) can be
      successfully used to evaluate the phagocytic activity in the atherosclerotic
      plaque in mice. In this study, we used 2 iron oxide-enhanced MRI strategies, in
      vivo labeling by injection of iron oxide particles and injection of in vitro
      labeled macrophages, to investigate the effect of irbesartan on both
      atherosclerotic plaque size and macrophage content in apolipoprotein (Apo) E
      deficient mice. MATERIALS AND METHODS: ApoE-/- female mice (C57BL/6 background;
      Charles-River, France) were divided into 2 groups (irbesartan treated [TG] or not
      treated [NTG]) and started on a high-fat diet (Harlan TD88137 Western Diet, 21%
      fat, 0.2% cholesterol). Animals underwent magnetic resonance examinations on a 7
      T scanner at baseline and at 14 and 28 weeks of treatment. At each time point, 2
      MRI sessions were performed, before and 48 hours after administration of an iron
      oxide agent (P904; Guerbet, France) or magnetically labeled macrophages (MFPhi).
      At the end of the follow-up, blood samples were taken for plasma lipid dosing and
      aorta samples for histology. The study was approved by the animal experimentation
      ethic committee of our institution.Vessel wall area measurements were performed
      on high-resolution spin echo transverse images. Multiecho gradient echo images
      acquired with the same geometry were used to calculate T2* maps of the vessel
      wall using a pixel-by-pixel monoexponential fit. Irbesartan effect on vessel wall
      area over time was assessed using a factorial analysis of variance test. T2*
      values of the vessel wall at pre- and post-ultrasmall superparamagnetic iron
      oxide (USPIO) administration were analyzed with a 1-way analysis of variance test
      with Bonferroni post hoc. RESULTS: Irbesartan treatment resulted in significantly
      smaller vessel wall areas at 28 weeks of treatment (P = 0.04). Postinjection
      values varied significantly over time for both the NTG-P904 (P = 0.02) and the TG
      P904 (P = 0.01) groups. Furthermore, when comparing the TG-P904 with the NTG-P904
      group at 28 weeks of treatment, a significant difference was obtained for both
      pre- and post-USPIO administration values (P = 0.01). In the labeled-macrophage
      group, postinjection T2* values were smaller than the preinjection ones for the
      NTG animals at 14 weeks of treatment. No T2* changes were observed in the TG-MPhi
      group.The difference between pre- and post-USPIO administration T2* values
      (DeltaT2*) was significantly smaller in the TG-P904 group compared with the NTG
      P904 group at 28 weeks of treatment. At this point, a good correlation (R = 0.7,
      P = 0.03) was found between the DeltaT2* values in the P904 imaging group and the
      macrophage-covered area by immunohistological analysis. CONCLUSIONS: The present
      study illustrates an MRI follow-up of intraplaque macrophages using in vivo
      labeling by iron oxide particle injection and macrophage injection after in vitro
      USPIO labeling in the assessment of a therapeutic effect in a mouse model of
      atherosclerosis. Even though in vivo labeling is not fully specific of macrophage
      uptake, it enabled the detection of a treatment-related reduction in the
      macrophage content of atherosclerotic plaques in ApoE-/- mice.

PMID- 22864379
TI  - VKORC1-dependent pharmacokinetics of intravenous and oral phylloquinone (vitamin
      K1) mixed micelles formulation.
AB  - OBJECTIVE: The pharmacokinetics of phylloquinone (vitamin K1) were evaluated in
      healthy human adult volunteers (15 male and 15 female) following oral and
      intravenous administration of a mixed micelles formulation (Konakion MM 2 mg) in
      an open label study design. The subjects were allocated to one of three genotype
      specific groups (n = 10 in each group) in terms of VKORC1 promoter polymorphism
      c.-1639 G > A to explore the relationship between genotype and pharmacokinetic
      parameters. METHODS: Blood samples were collected for up to 24 h after
      administration. Phylloquinone serum levels were determined by reversed phase HPLC
      with fluorometric detection after post-column zinc reduction. Pharmacokinetic
      evaluation was performed using non-compartmental analysis. RESULTS:
      Pharmacokinetic analysis of serum phylloquinone concentration versus time
      profiles revealed significant differences in the main pharmacokinetic parameters
      between groups. Upon oral administration, VKORC1 AG carriers showed 41 % higher
      mean bioavailability (p = 0.01) compared with homozygous AA individuals.
      Furthermore, AG subjects exhibited 30 % (p = 0.042) and 36 % (p = 0.021) higher
      mean AUC compared with GG and AA respectively. Terminal half-life was 32 % and 27
      % longer for AG carriers in comparison to GG (p = 0.004) and AA (p = 0.015)
      genotypes respectively. CONCLUSION: Pharmacokinetic differences indicated
      significant inter-individual variance of vitamin K fate in the human body. The
      influence of the VKORC1 promoter polymorphism c.-1639 G > A on the
      pharmacokinetic properties of phylloquinone could be demonstrated in humans. To
      gain deeper insight in other potential genetic determinants of systemic vitamin K
      exposure, further correlation of the phenotype-genotype relationship of different
      players in vitamin K turnover has to be gained.

PMID- 22864380
TI  - Potentially inappropriate medications in the elderly in France: a study in
      community pharmacies in 2011-2012.

PMID- 22864381
TI  - The glucose-deprivation network counteracts lapatinib-induced toxicity in
      resistant ErbB2-positive breast cancer cells.
AB  - Dynamic interactions between intracellular networks regulate cellular homeostasis
      and responses to perturbations. Targeted therapy is aimed at perturbing oncogene
      addiction pathways in cancer, however, development of acquired resistance to
      these drugs is a significant clinical problem. A network-based computational
      analysis of global gene expression data from matched sensitive and acquired drug
      resistant cells to lapatinib, an EGFR/ErbB2 inhibitor, revealed an increased
      expression of the glucose deprivation response network, including glucagon
      signaling, glucose uptake, gluconeogenesis and unfolded protein response in the
      resistant cells. Importantly, the glucose deprivation response markers correlated
      significantly with high clinical relapse rates in ErbB2-positive breast cancer
      patients. Further, forcing drug-sensitive cells into glucose deprivation rendered
      them more resistant to lapatinib. Using a chemical genomics bioinformatics mining
      of the CMAP database, we identified drugs that specifically target the glucose
      deprivation response networks to overcome the resistant phenotype and reduced
      survival of resistant cells. This study implicates the chronic activation of
      cellular compensatory networks in response to targeted therapy and suggests novel
      combinations targeting signaling and metabolic networks in tumors with acquired
      resistance.

PMID- 22864382
TI  - Effects of diet and development on the Drosophila lipidome.
AB  - Cells produce tens of thousands of different lipid species, but the importance of
      this complexity in vivo is unclear. Analysis of individual tissues and cell types
      has revealed differences in abundance of individual lipid species, but there has
      been no comprehensive study comparing tissue lipidomes within a single developing
      organism. Here, we used quantitative shotgun profiling by high-resolution mass
      spectrometry to determine the absolute (molar) content of 250 species of 14 major
      lipid classes in 6 tissues of animals at 27 developmental stages raised on 4
      different diets. Comparing these lipidomes revealed unexpected insights into
      lipid metabolism. Surprisingly, the fatty acids present in dietary lipids
      directly influence tissue phospholipid composition throughout the animal.
      Furthermore, Drosophila differentially regulates uptake, mobilization and tissue
      accumulation of specific sterols, and undergoes unsuspected shifts in fat
      metabolism during larval and pupal development. Finally, we observed striking
      differences between tissue lipidomes that are conserved between phyla. This study
      provides a comprehensive, quantitative and expandable resource for further
      pharmacological and genetic studies of metabolic disorders and molecular
      mechanisms underlying dietary response.

PMID- 22864383
TI  - Reverse engineering a hierarchical regulatory network downstream of oncogenic
      KRAS.
AB  - RAS mutations are highly relevant for progression and therapy response of human
      tumours, but the genetic network that ultimately executes the oncogenic effects
      is poorly understood. Here, we used a reverse-engineering approach in an ovarian
      cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and
      transcriptional networks from perturbation experiments based on gene silencing
      and pathway inhibitor treatments. We measured mRNA and protein levels in
      manipulated cells by microarray, RT-PCR and western blot analysis, respectively.
      The reconstructed model revealed complex interactions among the transcriptional
      and cytoplasmic components, some of which were confirmed by double pertubation
      experiments. Interestingly, the transcription factors decomposed into two
      hierarchically arranged groups. To validate the model predictions, we analysed
      growth parameters and transcriptional deregulation in the KRAS-transformed
      epithelial cells. As predicted by the model, we found two functional groups among
      the selected transcription factors. The experiments thus confirmed the predicted
      hierarchical transcription factor regulation and showed that the hierarchy
      manifests itself in downstream gene expression patterns and phenotype.

PMID- 22864385
TI  - Inheritance of grain polyphenol oxidase (PPO) activity in multiple wheat
      (Triticum aestivum L.) genetic backgrounds.
AB  - Grain polyphenol oxidase (PPO) activity can cause discoloration of wheat
      (Triticum aestivum L.) food products. Five crosses (PI 117635/Antelope;
      Fielder/NW03681; Fielder/Antelope; NW07OR1070/Antelope; NW07OR1066/OR2050272H)
      were selected to study the genetic inheritance of PPO activity. STS markers,
      PPO18, PPO29 and STS01, were used to identify lines with putative alleles at the
      Ppo-A1 and Ppo-D1 loci conditioning low or high PPO activity. ANOVA showed
      significant genotypic effects on PPO activity (P < 0.0001) in all populations.
      The generations and generation * genotype effects were not significant in any
      population. A putative third (null) genotype at Ppo-A1 (no PCR fragments for
      PPO18) was discovered in NW07OR1066 and NW07OR1070 derived populations, and these
      had the lowest mean PPO activities. Results demonstrated that both Ppo-A1 and Ppo
      D1 loci affect the kernel PPO activity, but the Ppo-A1 has the major effect. In
      three populations, contrary results were observed to those predicted from
      previous work with Ppo-D1 alleles, suggesting the markers for Ppo-D1 allele might
      give erroneous results in some genetic backgrounds or lineages. Results suggest
      that selection for low or null alleles only at Ppo-A1 might allow development of
      low PPO wheat cultivars.

PMID- 22864384
TI  - Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances
      efficacy in an in vivo model of arthritis.
AB  - Despite the clinical success of anti-tumor necrosis factor (TNF) therapies in the
      treatment of inflammatory conditions such as rheumatoid arthritis, Crohn disease
      and psoriasis, full control of the diseases only occurs in a subset of patients
      and there is a need for new therapeutics with improved efficacy against broader
      patient populations. One possible approach is to combine biological therapeutics,
      but both the cost of the therapeutics and the potential for additional toxicities
      needs to be considered. In addition to the various mediators of immune and
      inflammatory pathways, angiogenesis is reported to contribute substantially to
      the overall pathogenesis of inflammatory diseases. The combination of an anti
      angiogenic agent with anti-TNF into one molecule could be more efficacious
      without the risk of severe immunosuppression. To evaluate this approach with our
      Zybody technology, we generated bispecific antibodies that contain an Ang2
      targeting peptide genetically fused to the anti-TNF antibody adalimumab
      (Humira(r)). The bispecific molecules retain the binding and functional
      characteristics of the anti-TNF antibody, but with additional activity that
      neutralizes Ang2. In a TNF transgenic mouse model of arthritis, the bispecific
      anti-TNF-Ang2 molecules showed a dose-dependent reduction in both clinical
      symptoms and histological scores that were significantly better than that
      achieved by adalimumab alone.

PMID- 22864388
TI  - Low temperature rate constants for the N + CN -> N2 + C reaction: two-dimensional
      quantum capture calculations on an accurate potential energy surface.
AB  - The title reaction is thought to be responsible for the production of molecular
      nitrogen in interstellar clouds. In this work, we report quantum capture
      calculations on a new two-dimensional potential energy surface determined by
      interpolating high-level ab initio data. The low-temperature rate constant
      calculated using a capture model is quite large and has a positive temperature
      dependence, in agreement with a recent experiment. The origin of the
      aforementioned behaviors of the rate constant is analyzed.

PMID- 22864386
TI  - Mapping and characterization of the major quantitative trait locus qSS7
      associated with increased length and decreased width of rice seeds.
AB  - Seed shape in rice (Oryza sativa) is an important factor that determines grain
      appearance, cooking quality and grain yield. Here, we report a major quantitative
      trait locus qSS7 on the long arm of chromosome 7 for seed length, seed width and
      the ratio of seed length to width, identified using a segregating population
      derived from a cross between an indica variety Zhenshan97 and a chromosomal
      segment substitution line of a japonica variety Cypress within the genetic
      background of Zhenshan97. The Cypress allele at qSS7 contributes to an increase
      in seed length and the ratio of length to width, but a decrease in seed width,
      without significantly changing seed weight, plant height, heading date or number
      of spikelets per panicle. Using a large F(2) population generated from a
      substitution line that carries only a heterozygous single segment surrounding
      qSS7, we delimited the QTL to a 23-kb region containing two annotated genes.
      Progeny testing of the informative recombinants suggested that this qSS7 region
      is a composite QTL in which at least two genes contribute to seed length and
      width. Sequence comparison and expression analysis of two probable candidate
      genes revealed differences between the parental lines. These results will
      facilitate cloning of the gene(s) underlying qSS7 as well as marker-assisted
      transfer of desirable genes for seed shape in rice improvement.

PMID- 22864387
TI  - Comparative genomics to bridge Vicia faba with model and closely-related legume
      species: stability of QTLs for flowering and yield-related traits.
AB  - This study presents the development of an enhanced map in faba bean. The map
      contains 258 loci, mostly gene-based markers, organized in 16 linkage groups that
      expand 1,875 cM, with an average inter-marker distance of 7.26 cM. The
      combination of EST-derived markers with a number of markers physically located or
      previously ascribed to chromosomes by trisomic segregation, allowed the
      allocation of eight linkage groups (229 markers), to specific chromosomes.
      Moreover, this approach provided anchor points to establish a global homology
      among the faba bean chromosomes and those of closely-related legumes species. The
      map was used to identify and validate, for the first time, QTLs controlling five
      flowering and reproductive traits: days to flowering, flowering length, pod
      length, number of seeds per pod and number of ovules per pod. Twelve QTLs stable
      in the 2 years of evaluation were identified in chromosomes II, V and VI.
      Comparative mapping suggested the conservation of one of the faba bean genomic
      regions controlling the character days to flowering in other five legume species
      (Medicago, Lotus, pea, lupine, chickpea). Additional syntenic co-localizations of
      QTLs controlling pod length and number of seeds per pod between faba bean and
      Lotus japonicus are likely. The new genetic map opens the way for further
      translational studies between faba bean and related legume species, and provides
      an efficient tool for breeding applications such as QTL analysis and marker
      assisted selection.

PMID- 22864389
TI  - A human telomeric DNA-based chiral biosensor.
AB  - Here we report an electrochemical DNA (E-DNA) chiral sensor that can distinguish
      zinc-finger like metallo-supramolecular enantiomers based on human telomeric G
      quadruplex formation specifically induced by one of the enantiomers. The assay is
      easy to operate and reusable with an enantioselective recognition ratio higher
      than 5.

PMID- 22864390
TI  - Investigating the effect of macrocycle size in anion templated imidazolium-based
      interpenetrated and interlocked assemblies.
AB  - The effect of varying the size of the macrocycle component on the formation of
      anion templated imidazolium interpenetrated assemblies is investigated. Two
      different approaches to reducing the macrocycle size are undertaken and the
      stabilities of the resulting pseudorotaxanes incorporating substituted
      imidazolium threading components studied using (1)H NMR spectroscopy. Novel
      imidazolium axle containing interlocked rotaxane host structures are synthesised
      using chloride anion templated amide condensation and 'stoppering' methods, and
      the anion recognition properties of the 'stoppered' rotaxane investigated.

PMID- 22864391
TI  - H-point curve isolation method for determination of catechol in complex unknown
      mixtures.
AB  - In this work, the combination of H-point curve isolation method (HPCIM) and H
      point standard additions method (HPSAM) was used for determination of catechol in
      the presence of phenolic interferents. Spectrophotometric multivariate
      calibration data constructed by successive standard additions of an analyte in an
      unknown matrix was used by the method. A cumulative spectrum for interferents in
      sample was extracted by HPCIM and then HPSAM is used for determination of the
      catechol concentration by obtained cumulative interferents spectrum. The method
      was tested with simulated data set. The spectrum obtained from applying HPCIM to
      the simulated data well agrees with the cumulative spectra of the interferents.
      The method was applied to the determination of catechol in the presence of highly
      overlapping interferents in synthetic ternary mixtures using spectrophotometric
      data. Moreover, the proposed method was successfully used for determination of
      catechol in real complicated matrices of tea and urine samples. Percent
      recoveries were between 95.4 and 113.6.

PMID- 22864392
TI  - Combined experimental and theoretical approaches to the molecular structure of 4
      (1-formylnaphthalen-2-yloxy)phthalonitrile.
AB  - The novel compound 4-(1-formylnaphthalen-2-yloxy)phthalonitrile,
      C(19)H(10)N(2)O(2,) has been synthesized and characterized by IR, UV-vis, NMR and
      X-ray single-crystal determination. The title compound, is built up from two
      planar groups (naphthalen and phthalonitrile), with a dihedral angle of 64.10(4)
      degrees  between them. The crystal structure is stabilized by weak C-H...O
      hydrogen-bond and pi-pi interactions. The structural and spectroscopic data of
      the compound in the ground state have been calculated using density functional
      theory (DFT) and Hartree-Fock (HF) with the 6-31G(d,p) basis set. The vibrational
      study was interpreted in terms of potential energy distribution (PED). The
      observed wave number in FT-IR spectra was analyzed and assigned to different
      normal modes of the molecule. Using the TD-DFT and TD-HF methods, electronic
      absorption spectra of the title compound were predicted and good agreement with
      the TD-DFT method and the experimental determination was found. Isotropic
      chemical shifts ((13)C and (1)H NMR) were calculated using the gauge-invariant
      atomic orbital (GIAO) method. The HOMO and LUMO analyses were used to elucidate
      information regarding charge transfer within the molecule.

PMID- 22864393
TI  - Resonance-enhanced two-photon ionization spectroscopy and theoretical
      calculations of 3,5-difluoroanisole and its Ar-containing complex.
AB  - The structure and vibrations of 3,5-difluoroanisole (3,5-DFA) in the first
      electronically excited (S(1)) state were studied by mass-analyzed resonant two
      photon ionization (R2PI) technique as well as the quantum chemical calculations.
      The ab initio and density functional theory (DFT) calculations reveal that only
      one structure is stable for each of the S(0), S(1), and D(0) states. In the one
      color R2PI spectrum, the band origin of the S(1)<-S(0) electronic transition
      (0(0) band) of 3,5-DFA is found to be 37,595+/-3 cm(-1). In the S(1) state, most
      of the bands observed are related to the in-plane ring deformation and out-of
      plane bending vibrations. The adiabatic ionization energy (IE) of 3,5-DFA is
      determined to be 70,096+/-15 cm(-1) by the two color R2PI technique, in agreement
      with the values predicted by the DFT approaches. The dihalogen-substitution
      effects on the molecular structure, vibrational frequencies, and electronic
      transition and ionization energies were discussed in detail. The van der Waals
      complex of 3,5-DFA with argon (3,5-DFA...Ar) was also observed and studied. The
      0(0) band of 3,5-DFA...Ar complex is red-shifted by about 9 cm(-1) with respect
      to that of 3,5-DFA. Both the experimental data and the calculated results
      indicate that the formation of 3,5-DFA...Ar complex gives only a weak influence
      on the properties of 3,5-DFA moiety.

PMID- 22864394
TI  - DNA-binding, spectroscopic and antimicrobial studies of palladium(II) complexes
      containing 2,2'-bipyridine and 1-phenylpiperazine.
AB  - With the purpose of evaluating the ability of Pd(II) complex to interact with DNA
      molecule as the main biological target, two new complexes [Pd(bpy)(OH(2))(2)] (1)
      and [Pd(Phenpip)(OH(2))(2)] (2), where (bpy=2,2'-bipyridine; Phenpip=1
      phenylpiperazine), have been synthesized and the binding properties of these
      complexes with CT-DNA were investigated. The intrinsic binding constants (K(b))
      calculated from UV-Vis absorption studies were 3.78*10(3) M(-1) and 4.14*10(3)M(
      1) for complexes 1 and 2 respectively. Thermal denaturation has been
      systematically studied by spectrophotometric method and the calculated DeltaT(m)
      was nearly 5  degrees C for each complex. All the results suggest an
      electrostatic and/or groove binding mode for the interaction between the
      complexes and CT-DNA. The redox behavior of the two complexes in the absence and
      in the presence of calf thymus DNA has been investigated by cyclic voltammetry.
      The cyclic voltammogram exhibits one quasi-reversible redox wave. The change in
      E(1/2), DeltaE(p) and I(pc)/I(pa) supports that the two complexes exhibit strong
      binding to calf thymus DNA. Further insight into the binding of complexes with CT
      DNA has been made by gel electrophoresis, where the binding of complexes is
      confirmed through decreasing the intensity of DNA bands. The two complexes have
      been screened for their antimicrobial activities using the disc diffusion method
      against some selected Gram-positive and Gram-negative bacteria. The activity data
      showed that both complexes were more active against Gram-negative than Gram
      positive bacteria. It may be concluded that the antimicrobial activity of the
      compounds is related to cell wall structure of bacteria.

PMID- 22864395
TI  - A knockdown of Maml1 that results in melanoma cell senescence promotes an innate
      and adaptive immune response.
AB  - Maml1 is emerging as a coactivator of many signaling pathways, including the
      Notch and Wnt pathways. Targeting Maml1 in melanoma cells efficiently knocks down
      the downstream transcriptional repressors Hey1 and Hes1, resulting in melanoma
      cell senescence, cellular differentiation, and increased melanin production.
      Significantly, higher IFNbeta and chemokine gene transcripts have been observed,
      together with increased STAT1 and decreased STAT3 and NF-kappaB signaling
      activities. Although decreased cell proliferation contributes to slower tumor
      growth in vivo, the depletion of NK and CD8(+) T cells in an shMaml1-B16 tumor
      carrier mouse leads to more rapid tumor growth than that observed in control
      shC002-B16 tumors. This result demonstrates that the knockdown of Maml1
      transcription and function contributes to increased immune surveillance. The
      knockdown of Maml1 transcription in the human melanoma cell line M537 also
      results in senescence, IFNbeta upregulation, increased chemokine gene expression,
      and greater NK and CD8(+) T cell migration in a transwell system. This study
      demonstrated that targeting Maml1-induced tumor cell senescence and
      differentiation may alter the tumor microenvironment and cytokine and chemokine
      profiles and may also promote innate and adaptive immune cell infiltration and
      function.

PMID- 22864396
TI  - Rosiglitazone and Gemcitabine in combination reduces immune suppression and
      modulates T cell populations in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma is a leading cause of cancer mortality with a
      dismal 2-5 % 5-year survival rate. Monotherapy with Gemcitabine has limited
      success, highlighting the need for additional therapies that enhance the efficacy
      of current treatments. We evaluated the combination of Gemcitabine and
      Rosiglitazone, an FDA-approved drug for the treatment of type II diabetes, in an
      immunocompetent transplantable mouse model of pancreatic cancer. Tumor
      progression, survival, and metastases were evaluated in immunocompetent mice with
      subcutaneous or orthotopic pancreatic tumors treated with Pioglitazone,
      Rosiglitazone, Gemcitabine, or combinations of these. We characterized the impact
      of high-dose Rosiglitazone and Gemcitabine therapy on immune suppressive
      mediators, including MDSC and T regulatory cells, and on modulation of peripheral
      and intra-tumoral T cell populations. Combinations of Rosiglitazone and
      Gemcitabine significantly reduced tumor progression and metastases, enhanced
      apoptosis, and significantly extended overall survival compared to Gemcitabine
      alone. Rosiglitazone altered tumor-associated immune suppressive mediators by
      limiting early MDSC accumulation and intra-tumoral T regulatory cells.
      Combination therapy with Rosiglitazone and Gemcitabine modulated T cell
      populations by enhancing circulating CD8(+) T cells and intra-tumoral CD4(+) and
      CD8(+) T cells while limiting T regulatory cells. The results suggest that
      Rosiglitazone, in combination with Gemcitabine, decreases immune suppressive
      mechanisms in immunocompetent animals and provides pre-clinical data in support
      of combining Rosiglitazone and Gemcitabine as a clinical therapy for pancreatic
      cancer.

PMID- 22864397
TI  - The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity
      in cell lines and primary cultures of acute myeloid leukemia.
AB  - Aberrantly expressed tyrosine kinases have emerged as promising targets for drug
      development in acute myeloid leukemia (AML). We report that AKN-028, a novel
      tyrosine kinase inhibitor (TKI), is a potent FMS-like receptor tyrosine kinase 3
      (FLT3) inhibitor (IC(50)=6 nM), causing dose-dependent inhibition of FLT3
      autophosphorylation. Inhibition of KIT autophosphorylation was shown in a human
      megakaryoblastic leukemia cell line overexpressing KIT. In a panel of 17 cell
      lines, AKN-028 showed cytotoxic activity in all five AML cell lines included. AKN
      028 triggered apoptosis in MV4-11 by activation of caspase 3. In primary AML
      samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean
      IC(50) 1 MUM). However, no correlation between antileukemic activity and FLT3
      mutation status, or to the quantitative expression of FLT3, was observed.
      Combination studies showed synergistic activity when cytarabine or daunorubicin
      was added simultaneously or 24 h before AKN-028. In mice, AKN-028 demonstrated
      high oral bioavailability and antileukemic effect in primary AML and MV4-11
      cells, with no major toxicity observed in the experiment. In conclusion, AKN-028
      is a novel TKI with significant preclinical antileukemic activity in AML.
      Possible sequence-dependent synergy with standard AML drugs and good oral
      bioavailability has made it a candidate drug for clinical trials (ongoing).

PMID- 22864398
TI  - Power output in vertical jumps: does optimum loading depend on activity profiles?
AB  - The previously proposed maximum dynamic output hypothesis (MDO: i.e. the optimum
      load for maximizing the power output during jumping is one's own body) was tested
      on individuals of various activity profiles. Forty males (10 strength-trained
      athletes, 10 speed-trained athletes, 10 physically active non-athletes, and 10
      sedentary individuals) performed different vertical jumps on a force plate while
      a pulley system was used to either reduce or increase the subject's body weight
      by 10-30 %. As expected, an increase in external loading resulted in a
      significant increase (p < 0.001) in force output and a concomitant decrease of
      peak jumping velocity in all groups of participants. The main finding, however,
      was that all groups revealed the maximum peak and mean power output at
      approximately the subjects' own body weight although their weight represented
      prominently different percentage of their maximum dynamic strength. While a
      significant (p < 0.05), albeit moderate, 'group * load' interaction in one jump
      was observed for the peak power output, the individual optimum load for
      maximizing the power output number did not differ among the groups. Although
      apparently further research on various types of movements is needed, the present
      results provide, so far, the strongest support of the MDO hypothesis.

PMID- 22864399
TI  - Persistence on a stress-challenge task before initiating buprenorphine treatment
      was associated with successful transition from opioid use to early abstinence.
AB  - OBJECTIVES: Lapse to opiate use after initiation of buprenorphine treatment is
      common and is a strong predictor of poor treatment retention and increased risk
      of long-term opiate use. Drug cues and situations or events associated with
      distress are known to provoke craving and increase risk for lapse. This study
      evaluated the predictive validity of a behavioral index of persistence during a
      stress challenge among opiate users identified as affectively vulnerable to lapse
      risk due to elevated depressive symptoms. METHODS: Patients from an ongoing
      clinical trial (n = 48) completed a stress-challenge task before receiving their
      first dose of buprenorphine. RESULTS: After controlling for levels of craving on
      their induction day, persistence on the stress-challenge task before initiating
      buprenorphine treatment was associated with successful transition to early
      abstinence, and lower rates of opiate use during the initial 3 months of
      buprenorphine treatment across antidepressant and placebo groups. CONCLUSIONS:
      Results from this preliminary study suggest the promise of laboratory-based
      behavioral paradigms in facilitating an understanding of important mechanisms of
      early lapse. Identifying individual behavioral responses to drug and stress cues
      before attempts at abstinence may facilitate delivery of adjunctive behavioral
      treatments to prevent early lapse.

PMID- 22864400
TI  - Associations of functional and dysfunctional impulsivity to smoking
      characteristics.
AB  - OBJECTIVES: Although the relation between impulsivity and smoking is well
      documented, one model of impulsivity that has received little attention in the
      addiction literature separates impulsivity into 2 dimensions: functional
      impulsivity (tendency to make quick effective decisions) and dysfunctional
      impulsivity (tendency to make quick ineffective decisions). METHODS: This cross
      sectional study examined relations of functional and dysfunctional impulsivity to
      smoking characteristics in 212 non-treatment-seeking daily smokers (M = 15
      cigarettes per day, M age = 24 years, 53% women). RESULTS: Dysfunctional
      impulsivity exhibited small- to medium-sized positive associations with
      difficulty refraining from smoking in forbidden places, craving, and smoking
      without awareness. Functional impulsivity was inversely associated with a measure
      of cigarette craving. Other suggestive associations were found; however, these
      were not statistically significant after type I error correction. CONCLUSIONS:
      Although the overall predictive validity of these impulsivity constructs for
      explaining variance in smoking characteristics was relatively modest, the results
      suggest that conceptualizing impulsivity as a unitary construct indicative of a
      tendency to make quick decisions may mask heterogeneity within the impulsivity
      smoking relationship. These findings suggest that high-dysfunctional impulsivity
      smokers may perhaps require more intensive interventions to dampen motivation to
      smoke. They also highlight the possibility that certain manifestations of
      impulsivity are not related with increased smoking behavior and may actually
      associate with reduced drive to smoke.

PMID- 22864401
TI  - Engaging health professional students in substance abuse research: development
      and early evaluation of the SARET program.
AB  - OBJECTIVE: There is a need to build the ranks of health care professionals
      engaged in substance abuse (SA)-focused clinical research. The authors
      simultaneously developed and evaluated SARET, the Substance Abuse Research
      Education and Training program. The fundamental goal of this interprofessional
      program is to stimulate medical, dental, and nursing student interest and
      experience in SA research. Evaluation aims to understand program feasibility and
      acceptability and to assess short-term impact. METHODS: SARET comprises 2 main
      components: stipend-supported research mentorships and a Web-based module series,
      consisting of 6, interactive, multimedia modules addressing core SA research
      topics, delivered via course curricula and in the research mentorships. Authors
      assessed program feasibility and impact on student interest in conducting SA
      research by tracking participation and conducting participant focus groups and
      online surveys. RESULTS: Thirty early health care professional students completed
      mentorships (25 summer, 5 yearlong) and 1324 completed at least 1 Web-module.
      SARET was considered attractive for the opportunity to conduct clinically
      oriented research and to work with health care professionals across disciplines.
      Mentorship students reported positive impact on their vision of SA-related
      clinical care, more positive attitudes about research, and, in some cases, change
      in career plans. Web-based modules were associated with enhanced interest in SA
      (35% increase, P = 0.005, in those somewhat/very interested for neurobiology
      module) and SA research (+38%, P < 0.001 for activation, +45%, P < 0.001 for
      personal impact, +7%, P = 0.089 for neurobiology). CONCLUSIONS: The SARET program
      stimulates SA clinical and research interest among students of nursing, medicine,
      and dentistry and may lend itself to dissemination.

PMID- 22864402
TI  - Autologous fibroblast transplantation at the vesico-ureteral junction as
      potential reconstructive cell replacement in an animal model.
AB  - PURPOSE: To evaluate the cellular survival of donor fibroblasts after
      transplantation at the vesico-ureteral junction (VUJ) and to analyse their
      potential for reconstructive cell replacement in an animal model as autologous
      fibroblasts have been used as soft tissue augmentation material for scared and
      damaged tissue. METHODS: Muscles biopsies were procured from the lower limb
      muscles of 4 pigs; cytoplasm of fibroblasts was labelled with nano-sized iron
      oxide particles. Six weeks after taking of the muscle biopsies, fibroblast
      transplantation was performed, 3 * 10(6) cells suspended in transplantation
      medium (in 1-ml syringes) were injected at the VUJ using the modified STING
      technique. Animals were killed 8 weeks later; seeded fibroblasts were identified
      using prussian blue staining protocol; histological evaluation and morphological
      analysis were performed by light microscopy (Mayer's haematoxylin-eosin
      staining); and bladders were scanned by MRI for visualization and localization of
      the iron-labelled donor cells. RESULTS: Donor fibroblast cell colonization and
      cellular viability at the VUJ was demonstrated by MRI and histochemically
      indicating cellular uptake of iron particles at the VUJ. It was also evident that
      transplanted fibroblasts integrate into the extracellular matrix of the distal
      ureter augmenting ureteral host tissue. CONCLUSIONS: Labelled implanted
      autologous fibroblasts were visualized by staining procedure as well as MRI scan
      demonstrating persistence at the VUJ, suggesting that in vitro expanded
      fibroblasts survived in vivo after transplantation.

PMID- 22864403
TI  - Asymmetric construction of spirocyclohexanonerhodanines catalyzed by simple
      diamine derived from chiral tert-leucine.
AB  - A diamine-catalyzed asymmetric tandem reaction between alpha,beta-unsaturated
      ketones and rhodanine derivatives has been developed to synthesize various
      spirocyclic compounds with high stereoselectivities (up to 99% ee and >20:1 dr).
      The products obtained contain two pharmaceutically relevant features: the
      biologically active rhodanine moiety embedded in a spirocyclic unit.

PMID- 22864404
TI  - Low temperature kinetics of unstable radical reactions.
AB  - Recent advances in Earth and satellite based observations of molecules in
      interstellar environments and in planetary atmospheres have highlighted the lack
      of information regarding many important gas-phase formation mechanisms involving
      neutral species at low temperatures. Whilst significant progress has been made
      towards a better understanding of radical-molecule reactions in these regions,
      the inherent difficulties involved in the investigation of reactions between two
      unstable radical species have hindered progress in this area. This perspective
      article provides a brief review of the most common techniques applied to study
      radical-radical reactions below room temperature, before outlining the
      developments in our laboratory that have allowed us to extend such measurements
      to temperatures relevant to astrochemical environments. These developments will
      be discussed with particular emphasis on our recent investigations of the
      reactions of atomic nitrogen with diatomic radicals.

PMID- 22864405
TI  - Readability assessment of patient education materials on major otolaryngology
      association websites.
AB  - OBJECTIVE: Various otolaryngology associations provide Internet-based patient
      education material (IPEM) to the general public. However, this information may be
      written above the fourth- to sixth-grade reading level recommended by the
      American Medical Association (AMA) and National Institutes of Health (NIH). The
      purpose of this study was to assess the readability of otolaryngology-related
      IPEMs on various otolaryngology association websites and to determine whether
      they are above the recommended reading level for patient education materials.
      STUDY DESIGN AND SETTING: Analysis of patient education materials from 9 major
      otolaryngology association websites. METHODS: The readability of 262
      otolaryngology-related IPEMs was assessed with 8 numerical and 2 graphical
      readability tools. Averages were evaluated against national recommendations and
      between each source using analysis of variance (ANOVA) with post hoc Tukey's
      honestly significant difference (HSD) analysis. Mean readability scores for each
      otolaryngology association website were compared. RESULTS: Mean website
      readability scores using Flesch Reading Ease test, Flesch-Kincaid Grade Level,
      Coleman-Liau Index, SMOG grading, Gunning Fog Index, New Dale-Chall Readability
      Formula, FORCAST Formula, New Fog Count Test, Raygor Readability Estimate, and
      the Fry Readability Graph ranged from 20.0 to 57.8, 9.7 to 17.1, 10.7 to 15.9,
      11.6 to 18.2, 10.9 to 15.0, 8.6 to 16.0, 10.4 to 12.1, 8.5 to 11.8, 10.5 to 17.0,
      and 10.0 to 17.0, respectively. ANOVA results indicate a significant difference
      (P < .05) between the websites for each individual assessment. CONCLUSION: The
      IPEMs found on all otolaryngology association websites exceed the recommended
      fourth- to sixth-grade reading level.

PMID- 22864406
TI  - Acute otitis media in infants: the disease and the illness. Clinical distinctions
      for the new treatment paradigm.
AB  - Acute otitis media has changed conceptually from being a feared infection with
      severe complications to a modest disease that should be treated for symptomatic
      relief but often without immediate antimicrobials. This holds true for infants
      and children with nonsevere forms of the illness if the parents and the clinician
      agree to a strategy of watchful waiting with easy access for follow-up. Accurate
      otologic examination is critical for disease recognition, but the initial choice
      of treatment must also consider the general impact that the disease produces in
      each individual patient. The appraisal of the symptoms that characterize the
      illness in a child, matched with the otoscopic intensity of the disease, provide
      a comprehensive estimation of overall severity that many experts have used for
      research. The perspectives examined in this article and the schematic construct
      that proposes considering disease and illness independently may help to bring the
      current paradigm of acute otitis media into everyday pediatric practice as a
      model for a more rational and personalized management of each patient.

PMID- 22864407
TI  - The new ParaDIgm: IgM from bench to clinic: November 15-16, 2011, Frankfurt,
      Germany.
AB  - The inaugural IgM event entitled "The new ParaDIgm: IgM from bench to clinic"
      brought together the increasingly active and growing IgM antibody community to
      discuss recent advances and challenges facing the discovery and development of
      IgM antibody therapies and technologies. Researchers, clinicians and
      biomanufacturing experts delivered 21 talks on the basic science and isolation of
      IgM, upstream and downstream development, and formulation and clinical
      development of the molecules. Participants networked around topics aimed at
      exploring the full potential of IgM antibodies. The meeting was held at DECHEMA
      Gesellschaft fur Chemische Technik und Biotechnologie e. V. (Society for Chemical
      Engineering and Biotechnology), a non-profit scientific and technical society
      based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys,
      Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio
      Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic
      meeting, will be held on April 23-24, 2013 in Frankfurt, Germany.

PMID- 22864408
TI  - Sexual dimorphism of craniodental morphology in the raccoon dog Nyctereutes
      procyonoides from South Korea.
AB  - We examined sexual dimorphism in the craniodental traits of the raccoon dog
      Nyctereutes procyonoides from South Korea. Univariate comparisons of skull
      (cranium and mandible) and dental measurements revealed a small extent of sexual
      dimorphism in some measurements. The most indicative dimorphic measurements were
      the breadths of the upper and lower canines which were around 8% larger in male
      specimens on average. On the other hand, multivariate analyses using only skull
      traits showed slightly a clearer separation between sexes than those using only
      dental ones. This discrepancy may be derived from a higher variability in dental
      traits than in those of the skull. In conclusion, sexual dimorphism within N.
      procyonoides of South Korea is present, but was not so pronounced as for other
      local populations. However, measurements showing significant sexual dimorphism
      varied between different localities. This suggests that the selective forces
      acting upon craniodental morphology of each sex vary between populations of the
      species.

PMID- 22864410
TI  - WITHDRAWN: Incidence Study of Brucella abortus and Brucella melitensis in Bovine
      and Buffalo Semen Samples by Real-Time PCR Assay in Iran.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 22864409
TI  - Green tea catechins increase the force of contraction in isolated guinea pig
      atrial muscle preparations by increasing the amplitude of intracellular Ca2+
      concentration.
AB  - It has been reported that green tea catechins enhance the force of contraction of
      isolated heart muscle preparations. However, it remains controversial whether or
      not the increase in force of contraction is related to an increase in the
      intracellular Ca(2+) concentration ([Ca(2+)]i). In this study, the relationship
      was investigated using a left atrial muscle preparation isolated from guinea pig
      heart. In the left atrial muscle preparations without fura-2/AM loading, neither
      EGC (epigallocatechin) nor EC (epicatechin) influenced the force of contraction,
      but EGCG (epigallocatechin gallate) and ECG (epicatechin gallate) increased the
      force of contraction in a dose-dependent manner. The ED(50) value of EGCG was
      significantly higher than that of ECG. In the atrial muscle preparations loaded
      with fura-2/AM, EGCG and ECG increased the amplitude of [Ca(2+)]i(peak [Ca(2+)]i
      minus diastolic [Ca(2+)]i) which is associated with the increase in force of
      contraction. Simple regression analysis between the degree of increase in the
      force of contraction and the increase in the amplitude of [Ca(2+)]i revealed a
      positive correlation in EGCG, ECG and CaCl(2). In addition, the slopes of the
      regression lines of EGCG and ECG were comparable with those of CaCl(2). It was
      suggested that atrial muscle preparations had a higher affinity for ECG than
      EGCG, and that the increase in the force of contraction by EGCG and ECG was
      closely related to the increase in the amplitude of [Ca(2+)]i.

PMID- 22864411
TI  - Early-stage bioassay for monitoring radioactive contamination in living
      livestock.
AB  - Soil samples from the ground surface and feces and blood from a mixed-breed male
      pig were collected on April 10, 2011 at a farm within 20 km of the Fukushima
      Daiichi nuclear power plant. The radioactivity of each sample was measured using
      a Ge semiconductor detector. Despite the fact that the pig had been fed non
      contaminated imported feed, (131)I, (134)Cs and (137)Cs were detected in the
      feces, and (134)Cs and (137)Cs were detected in the blood clots. Because it is
      considerably difficult to measure radioactive contamination in the edible muscle
      of living livestock, bioassays are an option for the screening of radioactive
      contamination in living livestock to ensure food safety.

PMID- 22864412
TI  - A rotary microsystem for simple, rapid and automatic RNA purification.
AB  - In this work, we demonstrate a novel rotary microsystem for simple, rapid and
      automatic influenza viral RNA purification. The microdevice consists of a silica
      sol-gel matrix for RNA capture, and three reservoirs for a RNA sample (R(S)), a
      washing solution (R(W)) and an elution buffer (R(E)) that were connected with
      different dimensional microfluidic channels (120 MUm for R(S), 40 MUm for R(W),
      and 20 MUm for R(E)). The hydrophobic property of PDMS and the narrow
      microchannel served as a passive capillary microvalve, and the loading of the
      solutions were controlled by centrifugal force. 5 MUL of a lysate sample of
      influenza A H1N1 virus, a washing solution and an elution buffer were injected in
      each designated reservoir, and the virus sample, the washing solution, and the
      elution buffer were sequentially loaded into the sol-gel chamber at 1600, 2000,
      and 2500 RPM, enabling the viral RNA to be captured in the sol-gel solid phase,
      purified, and eluted in 5 min. The RNA capture yield was measured as ~80%, and
      the H1 and M gene were successfully amplified from the recovered purified H1N1
      viral RNA by reverse-transcriptase PCR. Such a novel rotary sample preparation
      system eliminates any complicated hardware and human intervention, and performs
      the RNA extraction with high speed and high fidelity.

PMID- 22864413
TI  - Chronological histological changes during bone regeneration on a non-crosslinked
      atelocollagen matrix.
AB  - Cleavage of the antigenic telopeptide region from type I collagen yields
      atelocollagen, and this is widely used as a scaffold for bone regeneration
      combined with cells, growth factors, etc. However, neither the biological effect
      of atelocollagen alone or its contribution to bone regeneration has been well
      studied. We evaluated the chronological histological changes during bone
      regeneration following implantation of non-crosslinked atelocollagen (Koken Co.,
      Ltd.) in rat calvarial defects. One week after implantation,  osteogenic cells
      positive for runt-related transcription factor 2 (Runx2) and osteoclasts positive
      for tartrate-resistant acid phosphatase (TRAP) were present in the atelocollagen
      implant in the absence of bone formation. The number of Runx2-positive osteogenic
      cells and Osterix-positive osteoblasts increased 2 weeks after implantation, and
      bone matrix proteins (osteopontin, OPN; osteocalcin, OC; dentin matrix protein 1,
      DMP1) were distributed in newly formed bone in a way comparable to normal bone.
      Some resorption cavities containing osteoclasts were also present. By 3 weeks
      after implantation, most of the implanted atelocollagen was replaced by new bone
      containing many resorption cavities, and OPN, OC, and DMP1 were deposited in the
      residual collagenous matrix. After 4 weeks, nearly all of the atelocollagen
      implant was replaced with new bone including hematopoietic marrow.
      Immunohistochemistry for the telopeptide region of type I collagen (TeloCOL1)
      during these processes demonstrated that the TeloCOL1-negative atelocollagen
      implant was replaced by TeloCOL1-positive collagenous matrix and new bone,
      indicating that new bone was mostly composed of endogenous type I collagen. These
      findings suggest that the atelocollagen itself can support bone regeneration by
      promoting osteoblast differentiation and type I collagen production.

PMID- 22864414
TI  - Anti-osteopenic effect of alpha-ketoglutarate sodium salt in ovariectomized rats.
AB  - The purpose of the study was to determine the effect of alpha-ketoglutarate
      sodium salt (AKG) treatment on the mineralization of the tibia in female rats
      during the development of osteopenia (Experiment-1) and in the condition of
      established osteopenia (Experiment-2). Thirty-two female rats were ovariectomized
      (OVX) to induce osteopenia and osteoporosis and another 32 female rats were sham
      operated (SHO) and then randomly divided between the two experiments. In
      Experiment-1, the treatment with AKG started after a 7-day period of
      convalescence, whereas in Experiment-2 the rats were subjected to a 60-day period
      of osteopenia fixation, after which the actual experimental protocol commenced.
      AKG was administered in the experimental solution for drinking at a concentration
      of 1.0 mol/l and a placebo (PLC) was used as a control solution. After 60 days of
      experimental treatment the rats in both experiements were sacrificed, the body
      weight recorded, and blood serum and isolated tibia were stored for further
      analysis. The bones were analyzed using tomography and densitometry, and for
      estimation of mechanical properties the 3-point bending test was used. Serum
      concentrations of osteocalcin and collagen type I crosslinked C-telopeptide were
      measured. The anabolic effects of AKG on bone during osteopenia development in
      Experiment-1 not only stopped the degradation of bone tissue, but also stimulated
      its mineralization. The usage of AKG in animals with established osteopenia
      (Experiment-2) was not able to prevent bone atrophy, but markedly reduced its
      intensity. The stimulation of tibia mineralization after AKG treatment has been
      also argued in healthy SHO animals. The results obtained prove the effectiveness
      of AKG usage in the prophylaxis and therapy of osteopenia and osteoporosis,
      induced by bilateral gonadectomy. Additionally, the results clearly prove that
      treatment with AKG improves the mineralization of bone tissue in healthy animals.

PMID- 22864415
TI  - Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias
      in injured hearts.
AB  - Transplantation studies in mice and rats have shown that human embryonic-stem
      cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted
      hearts, but two critical issues related to their electrophysiological behaviour
      in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM
      transplantation in injured hearts has not been determined. Second, the
      electromechanical integration of hESC-CMs in injured hearts has not been
      demonstrated, so it is unclear whether these cells improve contractile function
      directly through addition of new force-generating units. Here we use a guinea-pig
      model to show that hESC-CM grafts in injured hearts protect against arrhythmias
      and can contract synchronously with host muscle. Injured hearts with hESC-CM
      grafts show improved mechanical function and a significantly reduced incidence of
      both spontaneous and induced ventricular tachycardia. To assess the activity of
      hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically
      encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent
      signal with the host ECG, we found that grafts in uninjured hearts have
      consistent 1:1 host-graft coupling. Grafts in injured hearts are more
      heterogeneous and typically include both coupled and uncoupled regions. Thus,
      human myocardial grafts meet physiological criteria for true heart regeneration,
      providing support for the continued development of hESC-based cardiac therapies
      for both mechanical and electrical repair.

PMID- 22864416
TI  - The prokaryote messenger c-di-GMP triggers stalk cell differentiation in
      Dictyostelium.
AB  - Cyclic di-(3':5')-guanosine monophosphate (c-di-GMP) is a major prokaryote
      signalling intermediate that is synthesized by diguanylate cyclases and triggers
      sessility and biofilm formation. We detected the first eukaryote diguanylate
      cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium
      discoideum amoebas collect into aggregates, which first transform into migrating
      slugs and then into sessile fruiting structures. These structures consist of a
      spherical spore mass that is supported by a column of stalk cells and a basal
      disk. A polyketide, DIF-1, which induces stalk-like cells in vitro, was isolated
      earlier. However, its role in vivo proved recently to be restricted to basal disk
      formation. Here we show that the Dictyostelium diguanylate cyclase, DgcA,
      produces c-di-GMP as the morphogen responsible for stalk cell differentiation.
      Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and
      was expressed at the slug tip, which is the site of stalk cell differentiation.
      Disruption of the DgcA gene blocked the transition from slug migration to
      fructification and the expression of stalk genes. Fructification and stalk
      formation were restored by exposing DgcA-null slugs to wild-type secretion
      products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3':5')-adenosine
      monophosphate, induced stalk gene expression in dilute cell monolayers. Apart
      from identifying the long-elusive stalk-inducing morphogen, our work also
      identifies a role for c-di-GMP in eukaryotes.

PMID- 22864417
TI  - NRT/PTR transporters are essential for translocation of glucosinolate defence
      compounds to seeds.
AB  - In plants, transport processes are important for the reallocation of defence
      compounds to protect tissues of high value, as demonstrated in the plant model
      Arabidopsis, in which the major defence compounds, glucosinolates, are
      translocated to seeds on maturation. The molecular basis for long-distance
      transport of glucosinolates and other defence compounds, however, remains
      unknown. Here we identify and characterize two members of the nitrate/peptide
      transporter family, GTR1 and GTR2, as high-affinity, proton-dependent
      glucosinolate-specific transporters. The gtr1 gtr2 double mutant did not
      accumulate glucosinolates in seeds and had more than tenfold over-accumulation in
      source tissues such as leaves and silique walls, indicating that both plasma
      membrane-localized transporters are essential for long-distance transport of
      glucosinolates. We propose that GTR1 and GTR2 control the loading of
      glucosinolates from the apoplasm into the phloem. Identification of the
      glucosinolate transporters has agricultural potential as a means to control
      allocation of defence compounds in a tissue-specific manner.

PMID- 22864418
TI  - Prospective analysis of neutralising antibody titres in secondary non-responders
      under continuous treatment with a botulinumtoxin type A preparation free of
      complexing proteins--a single cohort 4-year follow-up study.
AB  - OBJECTIVES: In long-term botulinum neurotoxin treatment, loss of therapeutic
      efficacy may occur due to neutralising antibody formation. Preliminary results
      with incobotulinumtoxinA, a preparation free of complexing/accessory proteins,
      have indicated a low antigenicity. We hypothesised that continuous treatment with
      this botulinum neurotoxin preparation would not result in an increase in
      neutralising antibody titres (NABTs) in patients with pre-existing NABTs. DESIGN:
      Prospective, blinded cohort study. SETTING: Single centre in Germany.
      PARTICIPANTS: Thirty-seven cervical dystonia patients with NABTs and partial
      secondary non-responsiveness to their previous botulinum neurotoxin type A
      treatment. INTERVENTION: Three-monthly intramuscular injections of
      incobotulinumtoxinA with a constant dose of 200 MU per injection during the first
      year; thereafter up to 500 MU for the next 36 months. OUTCOME MEASURES:  PRIMARY
      OUTCOME MEASURE: number of patients in whom NABTs declined below the initial
      titre after 48 months of incobotulinumtoxinA treatment or in whom titres had
      become negative within the 48 months. SECONDARY OUTCOME MEASURE: steepness of
      changes in NABT. NABTs were determined by mouse hemidiaphragm assay. Findings
      were compared to long-term data from 24 cervical dystonia patients who had
      developed NABTs and in whom treatment had been discontinued. RESULTS: Following a
      transient increase in the first 24 months under incobotulinumtoxinA treatment in
      some patients, NABTs declined well below the initial titre in the majority of
      patients. Test assay results were negative in most of the patients followed for
      more than 36 months. NABTs seemed to decline into the negative detection range as
      rapidly under incobotulinumtoxinA treatment as after cessation of botulinum
      neurotoxin therapy. CONCLUSIONS: The reduction of NABTs despite continuous
      treatment with incobotulinumtoxinA indicates low antigenicity of
      incobotulinumtoxinA. This might have implications on restrictions such as minimum
      injection intervals of >=10 weeks currently in place for maintaining successful
      long-term application of botulinum neurotoxin.

PMID- 22864419
TI  - Evaluation of current Australian health service accreditation processes (ACCREDIT
      CAP): protocol for a mixed-method research project.
AB  - INTRODUCTION: Accreditation programmes aim to improve the quality and safety of
      health services, and have been widely implemented. However, there is conflicting
      evidence regarding the outcomes of existing programmes. The Accreditation
      Collaborative for the Conduct of Research, Evaluation and Designated
      Investigations through Teamwork-Current Accreditation Processes (ACCREDIT-CAP)
      project is designed to address key gaps in the literature by evaluating the
      current processes of three accreditation programmes used across Australian acute,
      primary and aged care services. METHODS AND DESIGN: The project comprises three
      mixed-method studies involving documentary analyses, surveys, focus groups and
      individual interviews. Study samples will comprise stakeholders from across the
      Australian healthcare system: accreditation agencies; federal and state
      government departments; consumer advocates; professional colleges and
      associations; and staff of acute, primary and aged care services. Sample sizes
      have been determined to ensure results allow robust conclusions. Qualitative
      information will be thematically analysed, supported by the use of textual
      grouping software. Quantitative data will be subjected to a variety of analytical
      procedures, including descriptive and comparative statistics. The results are
      designed to inform health system policy and planning decisions in Australia and
      internationally. ETHICS AND DISSEMINATION: The project has been approved by the
      University of New South Wales Human Research Ethics Committee (approval number
      HREC 10274). Results will be reported to partner organisations, healthcare
      consumers and other stakeholders via peer-reviewed publications, conference and
      seminar presentations, and a publicly accessible website.

PMID- 22864420
TI  - Oxidative degradation of chemical warfare agents in water by bleaching powder.
AB  - Degradation of sulfur mustard (HD), S-2-(di-isopropylamino)ethyl O-ethyl
      methylphosphonothioate (VX) and Soman (GD) in water by bleaching powder was
      investigated. The degradation products were comprehensively analyzed by gas
      chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry
      (LC/MS) and ion chromatography. Degradation pathways were deduced based on the
      identified products. The product analysis results indicated that HD could be
      degraded through oxidation and chlorination reactions, and a small portion of
      sulfur atoms could be mineralized into SO(4)(2-) ion. Oxidative degradation of VX
      could finally generate O-ethyl methylphosphonate acid (EMPA), sulfonic acids,
      SO(4)(2-) and NO(3)(-) ions. GD would be converted into non-toxic pinacolyl
      methylphosphonate via nucleophilic substitution.

PMID- 22864421
TI  - An advanced simulation model for membrane bioreactors: development, calibration
      and validation.
AB  - Membrane wastewater treatment plants (WWTPs) have several advantages compared
      with conventionally designed WWTPs with classical purification techniques. The
      filtration process is the key to their commercial success in Germany with respect
      to energy consumption and effectiveness, enabled by the optimization of
      filtration using a dynamic simulation model. This work is focused on the
      development of a robust, flexible and practically applicable membrane simulation
      model for submerged hollow-fibre and flat-sheet membrane modules. The model is
      based on standard parameters usually measured on membrane WWTPs. The performance
      of the model is demonstrated by successful calibration and validation for three
      different full-scale membrane WWTPs achieving good results. Furthermore, the
      model is combinable with Activated Sludge Models.

PMID- 22864422
TI  - Is a sequencing batch biofilter granular reactor suitable for textile wastewater
      treatment?
AB  - The textile industry releases highly polluted and complex wastewaters, which are
      difficult to treat and require numerous treatment steps. Innovative technologies
      for on-site treatment at each factory would permit cost reduction. For this
      reason, we ran a laboratory-scale study to assess the suitability of a sequencing
      batch biofilter granular reactor (SBBGR) for textile wastewater treatment,
      testing four different types of wastewater. Results demonstrate that wastewater
      characteristics greatly affect the reactor efficiency. Hence, a pre-study is
      advisable to define the best operational conditions and the maximum treatment
      capability for the wastewater under analysis. Nevertheless, SBBGR is a valuable
      biological treatment, effective in the reduction of pollutant load with stable
      performances despite the variability in wastewater composition. Tests with ozone
      integration have demonstrated that it is possible to dose small quantities of
      ozone to obtain an effluent suitable for direct discharge. However, a dynamic
      ozone dosage should be used to optimize the process as the correct ozone dose
      strongly depends on the wastewater composition.

PMID- 22864423
TI  - Olfactory and toxic impact of industrial odour emissions.
AB  - This paper describes the approach adopted for the evaluation both of the odour
      impact and of the non-carcinogenic health effects relevant to odours in the city
      of Terni, Italy. The first part of the study focused on the quantification of
      emissions by means of dynamic olfactometry and chemical analyses. Dispersion
      modelling was then applied for the evaluation of citizens' exposure both to
      odours and to their non-carcinogenic toxicity. The results show that, on one
      hand, the odour impact is considerable, actually affecting almost the whole city
      of Terni. On the other hand, the toxic impact, expressed in terms of the Hazard
      Index (HI), is about three orders of magnitude lower than the level that is
      expected to bring adverse effects, over a lifetime exposure, for human health.

PMID- 22864424
TI  - Methodological challenges in evaluating performance, impact and ranking of IWRM
      strategies in the Jordan Valley.
AB  - The philosophy of integrated water resource management (IWRM), as formulated in
      several international summits, yielded numerous interpretations and extensions
      over the last decade but always focused on the overall objective of maximizing
      the welfare and livelihood of the people concerned. One of the major constraints
      of this concept is the gap between the well-defined philosophy and the fuzzy
      definition of operational and testable indicators for the achievement of its
      goals. This leads to difficulties in the evaluation of potential contributions
      from technological and managerial improvements. The experience of the multi
      lateral IWRM research initiative SMART in the lower Jordan Valley shows that the
      evaluation and ranking of alternative IWRM strategies and their elements relies
      simultaneously on the identification of local goals and their interfaces with the
      superordinate national water sector policies. The documentation of the, still
      ongoing, development process of suitable assessment procedures describes their
      methodological embedding and conclusions drawn for the heterogeneous situation of
      water-related settings in this transboundary watershed.

PMID- 22864425
TI  - An OxiTop((r)) protocol for screening plant material for its biochemical methane
      potential (BMP).
AB  - A protocol was developed for determining the biochemical methane potential (BMP)
      of plant material using the OxiTop((r)) system. NaOH pellets for CO(2) absorption
      and different pretreatment methods were tested for their influence in the BMP
      test. The use of NaOH pellets in the headspace of the bottle negatively affected
      the stability of the test increasing the pH and inhibiting methanization. Sample
      comminution increased the biodegradability of plant samples. Our results clearly
      indicate the importance of test conditions during the assessment of anaerobic
      biodegradability of plant material, considering BMP differences as high as 44%
      were found. Guidelines and recommendations are given for screening plant material
      suitable for anaerobic digestion using the OxiTop((r)) system.

PMID- 22864426
TI  - Biofouling control by quorum sensing inhibition and its dependence on membrane
      surface.
AB  - Biofouling control by quorum sensing (QS) inhibition and the influence of
      membrane surface characteristics on biofilm formation and QS inhibition were
      investigated. Pseudomonas putida isolated from the bio-fouled reverse osmosis
      (RO) membranes in a real plant was used. Acylase was chosen as a model QS
      inhibitor. Bacteria on the membrane coupons were quantified with the
      heterotrophic plate count method. Cell distribution was imaged by a confocal
      laser scanning microscope. Results showed that biofilm formation on the membrane
      was reduced by acylase as it inhibits the activity of N-acylhomoserine lactone
      (AHL) which is a signal molecule of QS. It was also shown that membrane surface
      characteristics were influential factors affecting bacterial adhesion, biofilm
      formation, and QS inhibition.

PMID- 22864427
TI  - Acid Black 48 dye biosorption using Saccharomyces cerevisiae immobilized with
      treated sugarcane bagasse.
AB  - The textile industry consumes large quantities of water and chemicals, especially
      in dyeing and finishing processes. Textile dye adsorption can be accomplished
      with natural or synthetic compounds. Cell immobilization using biomaterials
      allows the reduction of toxicity and mechanical resistance and opens spaces
      within the matrix for cell growth. The use of natural materials, such as
      sugarcane bagasse, is promising due to the low costs involved. The aim of the
      present study was to evaluate the use of sugarcane bagasse treated with either
      polyethyleneimine (PEI), NaOH or distilled water in the cell immobilization of
      Saccharomyces cerevisiae for textile dye removal. Three different adsorption
      tests were conducted: treated sugarcane bagasse alone, free yeast cells and
      bagasse-immobilized yeast cells. Yeast immobilization was 31.34% with PEI-treated
      bagasse, 8.56% with distilled water and 22.54% with NaOH. PEI-treated bagasse
      exhibited the best removal rates of the dye at all pH values studied (2.50, 4.50
      and 6.50). The best Acid Black 48 adsorption rates were obtained with use of free
      yeast cells. At pH 2.50, 1 mg of free yeast cells was able to remove 5488.49 g of
      the dye. The lowest adsorption capacity rates were obtained using treated bagasse
      alone. However, the use of bagasse-immobilized cells increased adsorption
      efficiency from 20 to 40%. The use of immobilized cells in textile dye removal is
      very attractive due to adsorbed dye precipitation, which eliminates the
      industrial need for centrifugation processes. Dye adsorption using only yeast
      cells or sugarcane bagasse requires separation methods.

PMID- 22864428
TI  - Metal removal via particulate material in a lowland river system.
AB  - Twelve month surveys of acid-soluble and dissolved trace metal concentrations in
      the lower Waikato River (in 1998/9 and 2005/6) showed abnormally low particulate
      Fe, Mn, Cu, Pb and Zn concentrations and mass flux in autumn, when the suspended
      particulate material (SPM) had a relatively high diatom and organic carbon
      content, and low Fe and Al content. Dissolved Mn, Cu and Zn concentrations also
      decreased in autumn, while dissolved Fe and Pb concentrations were unaffected.
      While SPM settlement under the low river flow conditions present in autumn can
      explain the removal of particulate metals, it does not explain dissolved metal
      removal. SPM-metal interaction was therefore investigated using seasonal
      monitoring data, experimental adsorption studies, sequential extraction and
      geochemical modelling. Pb binding to SPM occurred predominantly via Fe-oxide
      surfaces, and could be reliably predicted using surface complexation adsorption
      modelling. Dissolved Mn concentrations were controlled by the solubility of Mn
      oxide, but enhanced removal during autumn could be attributed to uptake by
      diatoms. Zn and Cu were also adsorbed on Fe-oxide in the SPM, but removal from
      the water column in autumn appeared augmented by Zn adsorption onto Mn-oxide, and
      Cu adsorption onto the organic extracellular surfaces of the diatoms.

PMID- 22864429
TI  - On a QSAR approach for the prediction of priority compound degradation by water
      treatment processes.
AB  - Emerging (chemical) substances are increasingly found in water sources and must
      be removed by water treatment systems. However, the treatment efficiency
      regarding these substances is often unknown. A promising approach is using QSARs
      (quantitative structure activity relationships) or QSPRs (quantitative structure
      property relationships) to correlate the existing knowledge of a compound's
      chemical structure to water treatment process properties, such as a biological
      activity or physico-chemical property. As UV/H(2)O(2) treatment of water is an
      important barrier against priority pollutants, a QSAR model has been developed
      for the prediction of a typical physico-chemical property: i.e. hydroxyl radical
      reaction constants. Hydroxyl radicals are highly reactive and therefore largely
      responsible for a compound's degradation during UV/H(2)O(2) treatment. A good
      correlation is found for the training data set. Chemical parameters that were
      related to charge on C atoms and topology of the compound were found to be
      important for the hydroxyl radical rate constants. So far, these results look
      promising, but further research is still required to increase the predictability
      of the model and to develop QSAR models for other physico-chemical properties.

PMID- 22864430
TI  - Abu Dhabi's strategic tunnel enhancement programme: odour extraction system
      approaches.
AB  - The Emirate of Abu Dhabi has experienced tremendous growth since the mid-1970s
      resulting in significant overloading of its existing sewerage system. Master
      planning determined that the best long-term wastewater collection and conveyance
      solution was construction of a deep tunnel sewer system. Implementation of this
      massive project faced numerous challenges, including the goal of no odours and
      limited odour control facilities. To accomplish this, the consultant team
      examined a unique approach of a single odour control system installed at the
      proposed downstream tunnel pumping station. Rigorous analysis utilising computer
      based models confirmed the viability of this approach. However, other approaches
      including multiple satellite (localised or regional) odour extraction systems
      were considered. To better understand entrained air forces at vortex drops, and
      to confirm the preferred odour extraction approach, physical modelling of drop
      structures and overall tunnel system was implemented. Results and findings
      concluded that a regional odour extraction system approach was preferred over a
      single (centralised) extraction approach. This paper focuses on the process of
      selecting the preferred odour extraction approach and preliminary capacity sizing
      of regional systems.

PMID- 22864431
TI  - Characteristics of WWTP sludge after drying in greenhouse for agricultural
      purposes.
AB  - The sludge generated by sewage treatment which meets regulatory standards can be
      used in agriculture. With this understanding, the focus of this study is the
      evaluation of the agricultural characteristics and inorganic substances in excess
      activated sludge, which was subjected to drying in a greenhouse. The variables
      (factor) evaluated during the drying process were: type of sludge (digested or
      not digested), addition of lime to the sludge, and the physical layout and
      rotation of sludge in the greenhouse. The parameters monitored for this
      assessment were moisture, volatile solids and pH. The greenhouse cover and sides
      were made of translucent plastic to allow the penetration of solar radiation and
      prevent water from entering. A impermeable floor was used. The sludge was
      generated in sewage treatment plants located in the metropolitan region of Grande
      Vitoria, Espirito Santo, Brazil. The solar drying of wastewater sludge in a
      greenhouse presented satisfactory results.

PMID- 22864432
TI  - Identifiability analysis in conceptual sewer modelling.
AB  - For a sufficient calibration of an environmental model not only parameter
      sensitivity but also parameter identifiability is an important issue. In
      identifiability analysis it is possible to analyse whether changes in one
      parameter can be compensated by appropriate changes of the other ones within a
      given uncertainty range. Parameter identifiability is conditional to the
      information content of the calibration data and consequently conditional to a
      certain measurement layout (i.e. types of measurements, number and location of
      measurement sites, temporal resolution of measurements etc.). Hence the influence
      of number and location of measurement sites on the number of identifiable
      parameters can be investigated. In the present study identifiability analysis is
      applied to a conceptual model of a combined sewer system aiming to predict the
      combined sewer overflow emissions. Different measurement layouts are tested and
      it can be shown that only 13 of the most sensitive catchment areas (represented
      by the model parameter 'effective impervious area') can be identified when
      overflow measurements of the 20 highest overflows and the runoff to the waste
      water treatment plant are used for calibration. The main advantage of this method
      is very low computational costs as the number of required model runs equals the
      total number of model parameters. Hence, this method is a valuable tool when
      analysing large models with a long runtime and many parameters.

PMID- 22864433
TI  - A software-based sensor for combined sewer overflows.
AB  - A new methodology for online estimation of excess flow from combined sewer
      overflow (CSO) structures based on simulation models is presented. If sufficient
      flow and water level data from the sewer system is available, no rainfall data
      are needed to run the model. An inverse rainfall-runoff model was developed to
      simulate net rainfall based on flow and water level data. Excess flow at all CSO
      structures in a catchment can then be simulated with a rainfall-runoff model. The
      method is applied to a case study and results show that the inverse rainfall
      runoff model can be used instead of missing rain gauges. Online operation is
      ensured by software providing an interface to the SCADA-system of the operator
      and controlling the model. A water quality model could be included to simulate
      also pollutant concentrations in the excess flow.

PMID- 22864434
TI  - Effects of heat treatment on microbial communities of granular sludge for
      biological hydrogen production.
AB  - Dark fermentation shares many features with anaerobic digestion with the
      exception that to maximize hydrogen production, methanogens and hydrogen
      consuming bacteria should be inhibited. Heat treatment is widely applied as an
      inoculum pre-treatment due to its effectiveness in inhibiting methanogenic
      microflora but it may not exclusively select for hydrogen-producing bacteria.
      This work evaluated the effects of heat treatment on microbial viability and
      structure of anaerobic granular sludge. Heat treatment was carried out on
      granular sludge at 100  degrees C with four residence times (0.5, 1, 2 and 4 h).
      Hydrogen production of treated sludges was studied from glucose by means of batch
      test at different pH values. Results indicated that each heat treatment strongly
      influenced the granular sludge resulting in microbial communities having
      different hydrogen productions. The highest hydrogen yields (2.14 moles of
      hydrogen per mole of glucose) were obtained at pH 5.5 using the sludge treated
      for 4 h characterized by the lowest CFU concentration (2.3 * 10(3)CFU/g sludge).
      This study demonstrated that heat treatment should be carefully defined according
      to the structure of the sludge microbial community, allowing the selection of
      highly efficient hydrogen-producing microbes.

PMID- 22864435
TI  - Stabilization of source-separated urine by biological nitrification process:
      treatment performance and nitrite accumulation.
AB  - A laboratory study on nitrification of high-strength source-separated urine was
      conducted by means of sequencing batch reactors (SBR) and membrane bioreactors
      (MBR). The highest influent ammonia concentration for SBR and MBR reached more
      than 2,400 and 1,000 mg N/L, while the maximum pH was about 9 and 8.9,
      respectively. The ammonia oxidizing efficiency in both SBRs and MBRs was around
      50%, which was restrained mainly by the deficiency of alkalinity in bulks.
      Meanwhile, the nitrite accumulation did also dominate in these two systems, and
      the major factor to inhibit the nitrite oxidization was thought to be the high
      free ammonia and free nitrous acid content in bulks. Hence, an ammonia nitrite
      solution was achieved with concentration ratio of 1:1; after that ammonia
      oxidation was restrained owing to the deficiency of alkalinity in urine. The
      temperature and influent ammonia content have no great influence on the
      nitrification process in both kinds of bioreactors. The nitrification can be
      progressed under a solids retention time (SRT) longer than 30 d; however,
      termination of ammonia oxidization was observed as the SRT fell below 20 d. The
      nitrifier biomass showed an excellent settleability, such that the suspended
      solids (SS) in effluent was of a low average, about 60 mg/L. This study on the
      stabilization of human urine will be useful to understand the process of urine
      separation from source.

PMID- 22864436
TI  - Comparison of two peak-to-mean approaches for use in odour dispersion models.
AB  - In this paper, two approaches to estimate odour concentrations in dispersion
      models are compared. The approaches differ in the estimation of the momentary
      (peak) odour concentration for the time interval of a single human breath
      (approximately 5 s). The Austrian Odour Dispersion Model (AODM) is a Gaussian
      model with peak-to-mean factors depending on wind speed and atmospheric
      stability. The German Lagrange code AUSTAL2000 uses a constant factor 4 in all
      meteorological conditions to derive the maximum odour concentration over a short
      integration time. As the Lagrange model, in contrast to the Gauss model, can be
      applied also in complex topography and with isolated buildings, the
      implementation of the Austrian peak-to-mean approach in AUSTAL2000 would enable
      for more realistic separation distances in these environments. In a current
      scientific project, this implementation will be carried out, and a comparison of
      separation distances with AODM and AUSTAL2000 will be undertaken.

PMID- 22864437
TI  - Modeling mineral phase change chemistry of groundwater in a rural-urban fringe.
AB  - This research paper aims to determine the genetic origin of the chemical elements
      in groundwater. It deals with the results of physicochemical parameters, to
      evaluate the hydro-geochemistry of groundwater in rural-urban fringe of district
      Bareilly, India. Pre- and post-monsoon sampling has been carried out, which
      reveals inter-seasonal variability effect on the hydro-geochemical processes.
      Geochemical modeling especially computation of saturation index was undertaken
      using the WATEQ4F model. Majority of samples fall in the category of
      undersaturation, which further suggests that groundwater still has potential to
      dissolve more minerals. Chemical categorizations of groundwater samples were
      performed with the help of the Aquachem model. Grouping of groundwater on the
      Piper diagram reveals a common composition and origin. In most of the area, water
      facies is of Ca(2+)-HCO(3)(-) type in both the seasons. It also indicates that in
      pre-monsoon, ion exchange is the dominant process, whereas in post-monsoon, both
      ion exchanges as well as reverse ion exchanges are reported in the groundwater of
      the study area.

PMID- 22864438
TI  - Dissolved oxygen, COD, nitrogen and phosphorus profiles in a continuous sand
      filter used for WWTP effluent reclamation.
AB  - Continuous sand filtration (CSF) offers interesting potential for the extensive
      treatment of wastewater treatment plant (WWTP) effluents for water reclamation
      and/or restrictive discharge. Research on concentration profiles over the height
      of the CSF shows that most bacteriological conversions are restricted to the
      lower part of the filter bed. Dissolved oxygen (DO) rapidly decreases to below 1
      mg/L in the first 0.4 m of the filter bed, applying hydraulic velocities of 12.9
      ~ 14.9 m/h and 10 ~ 20 mm/min sand velocities, independent of the methanol
      dosage. The DO decrease agrees with the observed decrease in chemical oxygen
      demand (COD). At the given operational conditions, NO(x)-N and N-total removal is
      dedicated to the first 0.9 m of the filter bed. Results show that by optimising
      the CSF operational conditions the very restrictive effluent N and P values of
      2.2 and 0.15 mg/L, respectively, as described in the European Water Framework
      Directive, can be met.

PMID- 22864439
TI  - Inhibition effect of swine wastewater heavy metals and antibiotics on anammox
      activity.
AB  - The feasibility of anaerobic ammonium oxidation (anammox) process to treat
      wastewaters containing antibiotics and heavy metals (such as the liquid fraction
      of the anaerobically digested swine manure) was studied in this work. The
      specific anammox activity (SAA) was evaluated by means of manometric batch tests.
      The effects of oxytetracycline, sulfathiazole, copper and zinc were studied. The
      experimental data of the short-term assays were fitted with an inhibition model
      to identify the half maximal inhibitory concentration (IC(50)). After 24 h
      exposures, IC(50)-values equal to 1.9, 3.9, 650 and 1,100 mg L(-1) were
      identified for copper, zinc, sulfathiazole and tetracycline respectively. The
      effect of prolonged exposure (14 days) to oxytetracycline and sulfathiazole was
      studied by means of repeated batch-assays. Anabolism and catabolism reactions
      were active during the inhibition tests indicating that anammox bacteria could
      grow even in the extreme conditions tested. Considering the average
      concentrations expected in swine wastewaters, the inhibitors studied do not seem
      to represent a problem for the application of the anammox process. However, in
      order to verify the effect of these compounds on the growth of anammox bacteria,
      continuous culture experiments could be conducted.

PMID- 22864440
TI  - Impact of roof surface runoff on urban water quality.
AB  - The pollutant impacts of urban stormwater runoff on receiving waters are well
      documented in research literature. However, it is road surfaces that are commonly
      identified as the significant pollutant source. This paper presents the outcomes
      of an extensive program of research into the role of roof surfaces in urban water
      quality with particular focus on solids, nutrients and organic carbon. The
      outcomes confirmed that roof surfaces play an important role in influencing the
      pollutant characteristics of urban stormwater runoff. Pollutant build-up and wash
      off characteristics for roads and roof surfaces were found to be appreciably
      different. The pollutant wash-off characteristics exhibited by roof surfaces show
      that it influences the first flush phenomenon more significantly than road
      surfaces. In most urban catchments, as roof surfaces constitute a higher fraction
      of impervious area compared with road surfaces, it is important that the
      pollutant generation role of roof surfaces is specifically taken into
      consideration in stormwater quality mitigation strategies.

PMID- 22864441
TI  - Settlement as a driver for sewer rehabilitation.
AB  - This paper assesses the influence of (differential) settlement on sewer system
      functioning. Based on historical data of the vertical position of sewer invert
      levels, tilt measurements and in-sewer inspection videos, settlement and
      settlement related influences are analyzed for a case study area in Amsterdam.
      The average settlement rate of this system was 4 mm/year. Given this settlement
      rate, it is shown that settlement significantly influences sewer system
      functioning within the lifetime of a sewer (system).

PMID- 22864442
TI  - Nutrients budget and effluents characteristics in polyculture of scampi
      (Macrobrachium rosenbergii) and Indian major carps ponds using organic inputs.
AB  - Experiments were conducted for the study of nutrient budget in farmers' ponds
      (0.4-0.6 ha) in Orissa, India, at stocking densities of 0.30-0.38/m(2) for scampi
      (Macrobrachium rosenbergii) and 0.60-0.70/m(2) for Indian major carps (Catla
      catla, Labeo rohita and Cirrhinus mrigala). The average initial body weights of
      scampi and the major carps were 0.02 and 8-10 g, respectively. The culture period
      was 272-292 days. Feed was the main input. The FCR (feed conversion ratio) varied
      from 1.78 to 1.83. Feed and cow dung were applied to these ponds as organic
      inputs. At harvest time, the average weight of scampi and carps varied from 73 to
      92 g and from 718 to 820 g, respectively. Among all the inputs, feed alone
      accounted for 97.60% total nitrogen (N), 97.90% total phosphorus (P) and 94.72%
      total organic carbon (OC), respectively. The harvest of scampi and carps
      accounted for recovery of 52.45% N, 19.43% P and 18.12% OC, respectively. N, P
      and OC accumulated in sediment were 38.31, 71.40 and 69.50%, respectively. The
      median nutrient loads in the fish pond effluents were equivalent to 0.58 kg of
      inorganic N, 0.135 kg of P and 8.83 kg of total OC per ton of Indian major carps
      and scampi production.

PMID- 22864443
TI  - Numerical modelling of odour dispersion around a cubical obstacle using large
      eddy simulation.
AB  - In the present work two different large eddy simulation (LES) approaches, namely
      the Dynamic Smagorinsky model and the Wale model, are used to simulate the air
      flow and pollutant dispersion around a cubical obstacle. Results are compared
      with wind tunnel data (WT) and with results from the Smagorinsky LES model.
      Overall agreement was good between the different LES approaches and the WT
      results, both for the mean and fluctuating flow and concentration patterns. LES
      models can provide good estimates of concentration fluctuation intensity and
      enable the calculation of the intermittency factor. The model results indicate
      that LES is a viable tool for odour impact assessment.

PMID- 22864444
TI  - Comparison of extracellular polymeric substances (EPS) extraction from two
      different activated sludges.
AB  - The characteristics of extracellular polymeric substances (EPS) extracted with
      five different extraction protocols from two different activated sludges were
      studied. The results showed that the major EPS constituent extracted by
      centrifugation was protein for the sludge in sequencing batch reactor treating
      chemical wastewater, and nucleic acid for the sludge in moving bed biofilm
      reactor treating synthetic urban wastewater. The order of EPS extraction
      amounting from the two sludges was formaldehyde + NaOH > formaldehyde + heating >
      EDTA > heating > centrifugation. The different extraction methods, the wastewater
      type, and activated sludge source greatly affected the amount and composition of
      EPS. The chemical extracted methods were more effective than the physical methods
      in extracting EPS for the two sludges. Moreover, formaldehyde combined NaOH was
      most effective in extracting EPS for the two sludges. However, chemical
      extraction could contaminate the EPS solution, which was pointed out by infra-red
      analysis and was also proved by cell lyses during EPS extraction and carrying
      over of the chemical extractant. Therefore, this study highlights that the choice
      of EPS extraction method should consider both the extraction yield and content
      and the contamination of extracting reagents to the EPS solution. The extraction
      procedures should be optimized and most effective.

PMID- 22864445
TI  - Modelling sodium inhibition on the anaerobic digestion process.
AB  - Sodium is a known process inhibitor in anaerobic systems and impacts on
      methanogens through an increase of osmotic pressure or complete dehydration of
      microorganisms. In this study, a combination of experimental and modelling
      approaches has been employed to determine and simulate sodium inhibition on the
      anaerobic digestion process. The ADM1, which has been successfully used in
      modelling anaerobic processes, has been modified to include an extra inhibition
      function that considers the effect of sodium on acetoclastic methanogens and the
      impact on biogas production and composition. A non-competitive inhibition
      function was added to the rate of acetate uptake for the model to take into
      account sodium toxicity. Experimental studies consisted of both batch and reactor
      tests to obtain parameters for model calibration and validation. The calibrated
      model was used to predict the effect of ammonia nitrogen on sodium toxicity. It
      was found that relatively low sodium levels can bring about significant levels of
      process inhibition in the presence of high levels of ammonia. On the other hand,
      where the concentration of ammonia is relatively low, the tolerance threshold for
      sodium ions increases. Hence, care must be taken in the use of sodium hydroxide
      for pH adjustment during anaerobic digestion of protein-rich substrates.

PMID- 22864446
TI  - Development and validation of a UPLC-MS/MS method for studying the degradation
      kinetics of ofloxacin and trimethoprim during the application of solar Fenton
      process in secondary treated sewage.
AB  - In this work, a sensitive and highly selective method was developed and validated
      to study the degradation of two antibiotic compounds (ofloxacin (OFX) and
      trimethoprim (TMP)), spiked in secondary treated domestic effluents, by the solar
      Fenton process. Three different chromatographic columns were tested on a ultra
      performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS)
      instrument working in the electrospray ionization (ESI) mode with twelve
      combinations of eluting solvents. Samples were enriched prior to the analysis by
      solid phase extraction using the hydrophilic-lipophilic balanced (HLB) reversed
      phase polymeric sorbent. The method was optimized and showed very good
      performance characteristics and was successfully applied to study the degradation
      kinetics of the selected antibiotics during the solar Fenton process applied. The
      degradation was found to follow a pseudo first-order kinetics for both compounds
      at initial concentration of 100 MUg L(-1) with k = 0.0345 min(-1) for OFX and k =
      0.0768 min(-1) for TMP, whereas the complete removal was achieved after 120 min
      of treatment for both compounds.

PMID- 22864447
TI  - Zinc-sulphate-heptahydrate coated activated carbon for microbe removal from
      stormwater.
AB  - There is a need to develop effective stormwater filters for passive (without any
      addition of chemicals or energy) and effective removal of pathogens in order to
      mainstream stormwater harvesting. This study focuses on the development of coated
      granular activated carbon (GAC) filtration material in order to develop filters
      for effective removal of pathogens from urban stormwater. Several laboratory
      trials were performed to gauge the effectiveness of the filters, which use a
      mixture of the zinc-sulphate-heptahydrate coated GAC and sand, on the removal of
      Escherichia coli (E. coli) from semi-natural stormwater. On average, a 98%
      removal of the inflow concentration of E. coli was achieved. Furthermore, there
      was also an improvement of approximately 25% in the removal of phosphorous.
      However, it was found that the treated material was leaching zinc. It was
      important to determine whether the observed removal of E. coli was indirectly
      caused by the sampling methodology. The results showed that the inactivation of
      the E. coli in the collected sample was small compared with the inactivation
      which actually occurred within the filter. This provides much promise to the
      filter, but the presence of zinc in the outflow demonstrates the need for further
      investigation into the stabilisation of the coating process.

PMID- 22864448
TI  - Microbial community structure and performance of an anaerobic reactor digesting
      cassava pulp and pig manure.
AB  - Microbial community dynamics in response to changes in substrate types (i.e. pig
      manure (PM), cassava pulp (CP) and mixtures of PM and CP) were investigated in an
      anaerobic continuously stirred tank reactor (CSTR). Molecular identification of
      bacterial and archaeal domains were performed, using a 16S rDNA clone library
      with polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      screening and phylogenetic analysis. Analysis of bacterial clone libraries
      revealed that the differences in the community structure corresponded to the
      substrate types. However, the Bacteroidetes were the most abundant group in all
      substrates, followed by the Clostridia. With pure PM, the dominant bacterial
      groups were Bacteroidales, Clostridia and Paludibacter. With a co-substrate, at
      CP to PM (CP:PM) ratio of 50:50, the sequences analysis revealed the greatest
      diversity of bacterial communities at class level, and the sequences affiliated
      with Cytophaga sp. became an exclusive predominant. With CP alone, Bacteroides
      sp. was the dominant species and this reactor had the lowest diversity of
      bacteria. Archaea observed in the CSTR fed with all substrate types were
      Methanosaeta sp., Methanosaeta concilii and Methanospirillum hungatei. Among the
      Archaea, Methanosaeta sp. was the exclusive predominant. The relative
      distribution of Archaea also changed regarding to the substrate types.

PMID- 22864449
TI  - Assessment of odour and H(2)S impact in WWTPs by cryo-condensation.
AB  - Stability of gaseous samples is a major concern when dealing with odours and
      airborne pollutants sampling. In terms of odours, the representativeness of the
      sample can be very seriously compromised, despite the rigorous application of the
      maximum storage time established by EN-13725. The present paper is focused on the
      use of the cryo-condensation technique (Cryocore) for time-weighted-average (TWA)
      sampling in waste water treatment plants (WWTPs), with the aim of comparing the
      values of TWA odour and H(2)S concentration when using the Cryocore system and
      other well established sampling methods, such as those described in EN-13725 and
      passive sampling. The study showed comparable results when comparing all the
      methodologies tested.

PMID- 22864450
TI  - Erratum: Regulation of Leaf Morphology by MicroRNA394 and Its Target LEAF CURLING
      RESPONSIVENESS.

PMID- 22864451
TI  - Vascular expression and C-terminal sequence divergence of cytokinin response
      factors in flowering plants.
AB  - Cytokinin response factors (CRFs) are important transcription factors that form a
      side branch of the cytokinin signaling pathway and have been linked to cytokinin
      regulated processes during development. CRF proteins are defined as belonging to
      a specific transcription factor family by the presence of an AP2/ERF DNA-binding
      domain and can be distinguished within this family by a group-specific CRF domain
      involved in protein-protein interactions. Here we further delimit CRFs into five
      distinct clades (I-V) represented across all major angiosperm lineages. Protein
      sequences within each clade contain a clade-specific C-terminal region distinct
      from other CRFs, suggesting ancient evolutionary divergence and specialization
      within this gene family. Conserved patterns of transcriptional regulation support
      these clade divisions. Despite these important differences, CRFs appear to show
      preferential localization or targeting to vascular tissue in quantitative real
      time PCR and reporter line analyses of Arabidopsis thaliana and Solanum
      lycopersicum (tomato). Phloem tissue expression within the vasculature often
      appears the strongest in CRF reporter lines, and an analysis of CRF promoter
      sequences revealed conservation and significant enrichment of phloem targeting
      cis-elements, suggesting a potential role for CRFs in this tissue. An examination
      of CRF loss-of-function mutants from cytokinin-regulated clades revealed
      alterations in higher order vein patterning. This supports both the general link
      of CRFs to vascular tissue and clade-specific differences between CRFs, since
      alterations in vascular patterning appear to be clade specific. Together these
      findings indicate that CRFs are potential regulators of developmental processes
      associated with vascular tissues.

PMID- 22864453
TI  - Combination of microsecond and nanosecond pulsed electric field treatments for
      inactivation of Escherichia coli in water samples.
AB  - Inactivation of microorganisms with pulsed electric fields is one of the
      nonthermal methods most commonly used in biotechnological applications such as
      liquid food pasteurization and water treatment. In this study, the effects of
      microsecond and nanosecond pulses on inactivation of Escherichia coli in
      distilled water were investigated. Bacterial colonies were counted on agar
      plates, and the count was expressed as colony-forming units per milliliter of
      bacterial suspension. Inactivation of bacterial cells was shown as the reduction
      of colony-forming units per milliliter of treated samples compared to untreated
      control. According to our results, when using microsecond pulses the level of
      inactivation increases with application of more intense electric field strengths
      and with number of pulses delivered. Almost 2-log reductions in bacterial counts
      were achieved at a field strength of 30 kV/cm with eight pulses and a 4.5-log
      reduction was observed at the same field strength using 48 pulses. Extending the
      duration of microsecond pulses from 100 to 250 MUs showed no improvement in
      inactivation. Nanosecond pulses alone did not have any detectable effect on
      inactivation of E. coli regardless of the treatment time, but a significant 3-log
      reduction was achieved in combination with microsecond pulses.

PMID- 22864452
TI  - Molecular genetic analysis of phototropism in Arabidopsis.
AB  - Plant life is strongly dependent on the environment, and plants regulate their
      growth and development in response to many different environmental stimuli. One
      of the regulatory mechanisms involved in these responses is phototropism, which
      allows plants to change their growth direction in response to the location of the
      light source. Since the study of phototropism by Darwin, many physiological
      studies of this phenomenon have been published. Recently, molecular genetic
      analyses of Arabidopsis have begun to shed light on the molecular mechanisms
      underlying this response system, including phototropin blue light photoreceptors,
      phototropin signaling components, auxin transporters, auxin action mechanisms and
      others. This review highlights some of the recent progress that has been made in
      further elucidating the phototropic response, with particular emphasis on mutant
      phenotypes.

PMID- 22864454
TI  - Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel
      immunosuppressive therapies.
AB  - In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii
      pneumonia (PCP) is a well-known opportunistic infection, and its management has
      been established. However, PCP is an emerging threat to immunocompromised
      patients without HIV infection, such as those receiving novel immunosuppressive
      therapeutics for malignancy, organ transplantation, or connective tissue
      diseases. Clinical manifestations of PCP are quite different between patients
      with and without HIV infections. In patients without HIV infection, PCP rapidly
      progresses, is difficult to diagnose correctly, and causes severe respiratory
      failure with a poor prognosis. High-resolution computed tomography findings are
      different between PCP patients with HIV infection and those without. These
      differences in clinical and radiologic features are the result of severe or
      dysregulated inflammatory responses that are evoked by a relatively small number
      of Pneumocystis organisms in patients without HIV infection. In recent years, the
      usefulness of PCR and serum beta-D-glucan assay for rapid and noninvasive
      diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti
      Pneumocystis agents has been shown to be beneficial in some populations, the
      optimal dose and duration remain to be determined. Recent investigations revealed
      that Pneumocystis colonization is prevalent, and that asymptomatic carriers are
      at risk for developing PCP and can serve as the reservoir for the spread of
      Pneumocystis by person-to-person transmission. These findings suggest the need
      for chemoprophylaxis in immunocompromised patients without HIV infection,
      although its indication and duration are still controversial. Because a variety
      of novel immunosuppressive therapeutics have been emerging in medical practice,
      further innovations in the diagnosis and treatment of PCP are needed.

PMID- 22864455
TI  - Socioeconomic variation in uptake of colonoscopy following a positive faecal
      occult blood test result: a retrospective analysis of the NHS Bowel Cancer
      Screening Programme.
AB  - BACKGROUND: Bowel cancer is a serious health burden and its early diagnosis
      improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens
      with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals
      with a positive test result. Socioeconomic inequalities have been demonstrated
      for FOBt uptake, but it is not known whether they persist at the next stage of
      the screening pathway. The aim of this study was to assess the association
      between colonoscopy uptake and area socioeconomic deprivation, controlling for
      individual age and sex, and area ethnic diversity, population density, poor self
      assessed health, and region. METHODS: Logistic regression analysis of colonoscopy
      uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged
      between 60 and 69 years. RESULTS: Overall colonoscopy uptake was 88.4%.
      Statistically significant variation in uptake is found between quintiles of area
      deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9
      89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity
      (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4
      90%). CONCLUSION: Colonoscopy uptake is high. The variation in uptake by
      socioeconomic deprivation is small, as is variation by subgroups of age and sex,
      poor self-assessed health, ethnic diversity, population density, and region.

PMID- 22864457
TI  - The cementless Bicontact stem in a prospective dual-energy X-ray absorptiometry
      study.
AB  - PURPOSE: The cementless Bicontact total hip arthroplasty (THA) system (AESCULAP
      AG, Tuttlingen, Germany) was introduced in 1986/1987 and has been in successful
      clinical use in an unaltered form up to today. Although good long-term results
      with the Bicontact stem have been published, it is questionable whether the
      implant provides the criteria for a state-of-the-art stem regarding proximal bone
      stock preservation. The purpose of the study was to monitor the periprosthetic
      bone mineral density (BMD) in a prospective two-year follow-up dual-energy X-ray
      absorptiometry (DEXA) study. METHODS: After power analysis, a consecutive series
      of 25 patients with unilateral Bicontact stem implantation was examined
      clinically and underwent DEXA examinations. Scans of seven regions of interest
      were taken preoperatively and at one week, six months, and one and two years.
      RESULTS: One patient required stem revision due to a deep infection. The Harris
      Hip Score increased significantly by 44 points. The most significant bone loss
      was observed in the calcar region (R7) in the first six months (-19.2 %). It
      recovered in the following 18 months to -8.5 %. The BMD in the greater trochanter
      dropped significantly after six months and remained stable at this level. BMD
      exceeded baseline values in distal regions and even more in the lesser trochanter
      region after two years. CONCLUSIONS: We conclude that the Bicontact stem provides
      adequate proximal bone stock preservation. We observed some signs of stress
      shielding at the tip of the stem, which is inevitable to some degree in THA with
      cementless straight stems. However, in this prospective DEXA investigation, we
      showed that proximal off-loading does not occur after THA with the Bicontact
      system. Thus, we believe that this stem is still a state-of-the-art implant.

PMID- 22864456
TI  - Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised
      clinical trial.
AB  - BACKGROUND: The role of systematic aortic and pelvic lymphadenectomy (SAPL) at
      second-look surgery in early stage or optimally debulked advanced ovarian cancer
      is unclear and never addressed by randomised studies. METHODS: From January 1991
      through May 2001, 308 patients with the International Federation of Gynaecology
      and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to
      undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point
      was overall survival (OS). RESULTS: The median operating time, blood loss,
      percentage of patients requiring blood transfusions and hospital stay were higher
      in the SAPL than in the control arm (P<0.001). The median number of resected
      nodes and the percentage of women with nodal metastases were higher in the SAPL
      arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median
      follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed,
      and 124 patients had died. Sites of first recurrences were similar in both arms.
      The adjusted risk for progression and death were not statistically different
      (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59;
      P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for
      death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and
      in the control arm, respectively). CONCLUSION: SAPL in second-look surgery for
      advanced ovarian cancer did not improve PFS and OS.

PMID- 22864458
TI  - Total hip replacement arthroplasty with Mallory-Head system--minimum ten-year
      follow-up results.
AB  - PURPOSE: The purpose of this study was to assess the clinical and radiographic
      results of a total hip arthroplasty with the double tapered Mallory-Head system.
      METHODS: The clinical and radiographic results of a consecutive series of 81
      total hip replacements in 75 patients were reviewed 10-15 years (average 11.4
      years) postoperatively. The patients' underlying conditions were avascular
      necrosis in 46 hips (57 %), osteoarthritis in 12 hips (15 %), RA in nine hips (11
      %), and others. Clinical results were evaluated based on the modified Harris hip
      score and modified Merle d'Aubigne-Postel score. A radiographic analysis was
      performed. RESULTS: The average modified Harris hip score improved from a
      preoperative score of 56 points to a postoperative 92 points. The average
      modified Merle d'Aubigne-Postel score was 15 points at the latest follow up, and
      55 hips (68 %) were classified as the clinical grades of excellent or good
      results. One acetabular component was revised because of loosening, and one was
      revised for recurrent dislocation. CONCLUSION: The clinical and radiological
      evaluations of the total hip replacements using the Mallory-Head system showed
      good results.

PMID- 22864459
TI  - Is mitochondrial DNA turnover slower than commonly assumed?
AB  - Mutations arise during DNA replication due to oxidative lesions and intrinsic
      polymerase errors. Mitochondrial DNA (mtDNA) mutation rate is therefore closely
      linked to the mitochondrial DNA turnover process, especially in post mitotic
      cells. This makes the mitochondrial DNA turnover rate critical for understanding
      the origin and dynamics of mtDNA mutagenesis in post mitotic cells. Experimental
      mitochondrial turnover quantification has been based on different mitochondrial
      macromolecules, such as mitochondrial proteins, lipids and DNA, and the
      experimental data suggested highly divergent turnover rates, ranging from over 2
      days to about 1 year. In this article we argue that mtDNA turnover rate cannot be
      as fast as is often envisaged. Using a stochastic model based on the chemical
      master equation, we show that a turnover rate corresponding to mtDNA half-life in
      the order of months is the most consistent with published mtDNA mutation levels.

PMID- 22864460
TI  - The five times sit to stand test in senior athletes.
AB  - BACKGROUND AND PURPOSE: The Five Times Sit to Stand Test (FTSST) has been
      established as a valid and reliable functional measure for older adults. Norms
      have been clearly defined for community-dwelling older adults and can be useful
      in the identification of mobility decline and prediction of future disability.
      However, because of the high rates of inactivity in the population of community
      dwelling older adults, it seems inappropriate to compare high-functioning older
      adults, for example, senior athletes, to these norms. With trends showing
      increased senior athlete participation, new norms may be necessary to
      appropriately evaluate this population of older adults. The purpose of this study
      was to (1) compare results of the FTSST in senior athletes older than 60 years to
      norms for community-dwelling adults of the same age (2) determine the effects of
      age, gender, and sport intensity on FTSST performance in senior athletes, and (3)
      establish norms appropriate for this population of interest. METHODS: The FTSST
      was performed on 276 (104 men, 172 women) senior athletes age 50 to 91 years
      (mean age = 64.9, SD = 15) reporting an average of 4 hours of cardiovascular
      training and 1 hour of strength training each week. All were actively engaged in
      national or state senior game competitions. RESULTS: All participants were able
      to complete the test. One hundred ninety-four participants between 60 and 89
      years of age showed significantly faster times than currently reported norms.
      Performance was negatively associated with age, but did not differ significantly
      between genders. Participants in more physically demanding sports did show the
      best FTSST times, although athletes engaged in more leisure sports still
      outperformed norms for community-dwelling seniors. CONCLUSION: Senior athletes
      show significantly greater FTSST speed than norms derived from community-dwelling
      older adults. New normative guidelines are presented to assist the screening of
      these athletes on this functional performance measure.

PMID- 22864461
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) in an Austrian urological
      department: 10 years experience covering 95.161 patients.
AB  - PURPOSE: So far, few data is available on Methicillin-resistant Staphylococcus
      aureus (MRSA) infections in urology. To obtain a better insight into MRSA
      infections, we studied prevalence, colonization and infection site and clinical
      implications of MRSA in a urological department over a 10-year period. METHODS: A
      retrospective study of all patients diagnosed with MRSA for the first time over a
      10-year period was set-up. RESULTS: Between 2000 and 2009, a total of 95.161 in-
      and outpatients were seen at our department. The prevalence of patients with
      newly diagnosed MRSA was low, that is, <0.1 % per year (mean 0.07%, 0.02-0.1 %).
      In total, 62 MRSA cases were identified over a 10-year period. MRSA incidence was
      10 times higher in inpatients (0.2 %) than in outpatients (0.02 %). Asymptomatic
      MRSA colonization was present in 25/62 patients (40.3 %), the remaining 59.7 %
      (37/62) showed clinical symptoms: MRSA positive swabs from open wounds were seen
      in 10/62 patients (16.1 %). Urinary tract infections were seen in 26/10 patients
      (41.9 %), while life-threatening MRSA sepsis occurred in one patient only over a
      decade. CONCLUSIONS: In summary, we observed very low rates of MRSA colonization
      and infection. Still, complications like delayed wound healing, development of
      abscess and even sepsis may occur.

PMID- 22864462
TI  - A pH-responsive fluorescent probe and photosensitiser based on a self-quenched
      phthalocyanine dimer.
AB  - A self-quenched zinc(II) phthalocyanine dimer linked with an acid-sensitive ketal
      unit has been prepared, which can be activated in an acidic environment (pH = 5.0
      6.5) as a result of the cleavage of the ketal linker and separation of the
      phthalocyanine units, resulting in enhanced fluorescence emission and singlet
      oxygen production.

PMID- 22864463
TI  - Impact of transcription factor 7-like 2 (TCF7L2) on pancreatic islet function and
      morphology in mice and men.
AB  - Common genetic variations in the gene encoding transcription factor 7-like 2
      (TCF7L2) reveal the strongest association with type 2-diabetes known to date.
      These lead to impaired insulin production and output, but the mechanisms of
      disease remain incompletely known. In this issue of Diabetologia, two
      publications provide new insights into TCF7L2-dependent diabetes.

PMID- 22864464
TI  - Cognitive behavioural treatments have long-term benefits in female rape survivors
      with post-traumatic stress disorder.

PMID- 22864466
TI  - Surface morphology and surface energy of anode materials influence power outputs
      in a multi-channel mediatorless bio-photovoltaic (BPV) system.
AB  - Bio-photovoltaic cells (BPVs) are a new photo-bio-electrochemical technology for
      harnessing solar energy using the photosynthetic activity of autotrophic
      organisms. Currently power outputs from BPVs are generally low and suffer from
      low efficiencies. However, a better understanding of the electrochemical
      interactions between the microbes and conductive materials will be likely to lead
      to increased power yields. In the current study, the fresh-water, filamentous
      cyanobacterium Pseudanabaena limnetica (also known as Oscillatoria limnetica) was
      investigated for exoelectrogenic activity. Biofilms of P. limnetica showed a
      significant photo response during light-dark cycling in BPVs under mediatorless
      conditions. A multi-channel BPV device was developed to compare quantitatively
      the performance of photosynthetic biofilms of this species using a variety of
      different anodic conductive materials: indium tin oxide-coated polyethylene
      terephthalate (ITO), stainless steel (SS), glass coated with a conductive polymer
      (PANI), and carbon paper (CP). Although biofilm growth rates were generally
      comparable on all materials tested, the amplitude of the photo response and
      achievable maximum power outputs were significantly different. ITO and SS
      demonstrated the largest photo responses, whereas CP showed the lowest power
      outputs under both light and dark conditions. Furthermore, differences in the
      ratios of light : dark power outputs indicated that the electrochemical
      interactions between photosynthetic microbes and the anode may differ under light
      and dark conditions depending on the anodic material used. Comparisons between
      BPV performances and material characteristics revealed that surface roughness and
      surface energy, particularly the ratio of non-polar to polar interactions (the CQ
      ratio), may be more important than available surface area in determining
      biocompatibility and maximum power outputs in microbial electrochemical systems.
      Notably, CP was readily outperformed by all other conductive materials tested,
      indicating that carbon may not be an optimal substrate for microbial fuel cell
      operation.

PMID- 22864465
TI  - A randomized, double-blind placebo-controlled trial of oral creatine monohydrate
      augmentation for enhanced response to a selective serotonin reuptake inhibitor in
      women with major depressive disorder.
AB  - OBJECTIVE: Antidepressants targeting monoaminergic neurotransmitter systems,
      despite their immediate effects at the synaptic level, usually require several
      weeks of administration to achieve clinical efficacy. The authors propose a
      strategy of adding creatine monohydrate (creatine) to a selective serotonin
      reuptake inhibitor (SSRI) in the treatment of patients with major depressive
      disorder. Such augmentation may lead to a more rapid onset of antidepressant
      effects and a greater treatment response, potentially by restoring brain
      bioenergetics at the cellular level. METHOD: Fifty-two women with major
      depressive disorder were enrolled in an 8-week double-blind placebo-controlled
      clinical trial and randomly assigned to receive escitalopram in addition to
      either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily
      assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score.
      RESULTS: In comparison to the placebo augmentation group, patients receiving
      creatine augmentation showed significantly greater improvements in HAM-D score,
      as early as week 2 of treatment. This differential improvement favoring creatine
      was maintained at weeks 4 and 8. There were no differences between treatment
      groups in the proportion of patients who discontinued treatment prematurely
      (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all
      reported adverse events (creatine: 36 events; placebo: 45 events). CONCLUSIONS:
      The current study suggests that creatine augmentation of SSRI treatment may be a
      promising therapeutic approach that exhibits more rapid and efficacious responses
      in women with major depressive disorder.

PMID- 22864467
TI  - Insect-inspired high-speed motion vision system for robot control.
AB  - The mechanism for motion detection in a fly's vision system, known as the
      Reichardt correlator, suffers from a main shortcoming as a velocity estimator:
      low accuracy. To enable accurate velocity estimation, responses of the Reichardt
      correlator to image sequences are analyzed in this paper. An elaborated model
      with additional preprocessing modules is proposed. The relative error of velocity
      estimation is significantly reduced by establishing a real-time response-velocity
      lookup table based on the power spectrum analysis of the input signal. By
      exploiting the improved velocity estimation accuracy and the simple structure of
      the Reichardt correlator, a high-speed vision system of 1 kHz is designed and
      applied for robot yaw-angle control in real-time experiments. The experimental
      results demonstrate the potential and feasibility of applying insect-inspired
      motion detection to robot control.

PMID- 22864468
TI  - Active inference and agency: optimal control without cost functions.
AB  - This paper describes a variational free-energy formulation of (partially
      observable) Markov decision problems in decision making under uncertainty. We
      show that optimal control can be cast as active inference. In active inference,
      both action and posterior beliefs about hidden states minimise a free energy
      bound on the negative log-likelihood of observed states, under a generative
      model. In this setting, reward or cost functions are absorbed into prior beliefs
      about state transitions and terminal states. Effectively, this converts optimal
      control into a pure inference problem, enabling the application of standard
      Bayesian filtering techniques. We then consider optimal trajectories that rest on
      posterior beliefs about hidden states in the future. Crucially, this entails
      modelling control as a hidden state that endows the generative model with a
      representation of agency. This leads to a distinction between models with and
      without inference on hidden control states; namely, agency-free and agency-based
      models, respectively.

PMID- 22864469
TI  - A phase I study of IMP321 and gemcitabine as the front-line therapy in patients
      with advanced pancreatic adenocarcinoma.
AB  - PURPOSE: This phase I study was conducted to determine the safety profile and
      maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3
      (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in
      patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients
      with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000
      mg/m(2))(level 1), gemcitabine (1,000 mg/m(2)) plus IMP 321 at 0.5 mg (level 2)
      and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers
      at baseline and post treatment were assessed. RESULTS: A total of 18 patients
      were enrolled to the study, and 17 were evaluable for toxicity. None of the 6
      patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of
      the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1
      reported hot flashes and 2 had mild pain at the injection sites. No severe
      adverse events previously attributed to IMP321 were observed. No significant
      differences were observed when comparing pre- and post-treatment levels of
      monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets
      (CD4, CD8). CONCLUSIONS: IMP321 in combination with gemcitabine is a well
      tolerated regimen. IMP321 did not result in any severe adverse events. No
      incremental activity observed for the additional IMP 321 to gemcitabine at the
      dose levels evaluated, likely due to sub-optimal dosing. Immunological markers
      suggested that higher dose levels of IMP321 are needed for future clinical
      studies.

PMID- 22864470
TI  - Water versus land-based multimodal exercise program effects on body composition
      in breast cancer survivors: a controlled clinical trial.
AB  - GOALS OF WORK: Our aim was to compare the effects of land versus water multimodal
      exercise programs on body composition and breast cancer-specific quality of life
      in breast cancer survivors. PATIENTS AND METHODS: Ninety-eight breast cancer
      survivors were assigned to three groups: control, land exercise, and water
      exercise. Both exercise groups participated in an 8-week multimodal program.
      Adiposity was measured by anthropometry (body mass index, waist circumference)
      and bioelectrical impedance (body fat and muscle lean body mass). Incidence of
      clinically significant secondary lymphedema was also assessed. Finally, specific
      quality of life was assessed using the European Organization for Research and
      Treatment of Cancer Quality of Life BR-23. MAIN RESULTS: Using ANCOVA,
      significant group * time interactions for body fat percentage (F = 3.376; P =
      0.011) and lean body mass (F = 3.566; P = 0.008) were found. Breast cancer
      survivors in the land exercise group exhibited a greater decrease in percentage
      of body fat than those in the water exercise (P < 0.001) and control (P = 0.002)
      groups. The ANCOVA revealed a significant group * time interaction for waist
      circumference (F = 4.553; P = 0.002): breast cancer survivors in the control
      group showed a greater waist circumference when compared to water (P = 0.003) and
      land (P < 0.001) exercise groups. A significant group * time interaction was also
      found for breast symptoms (F = 9.048; P < 0.001): participants in the water
      exercise group experienced a greater decrease of breast symptoms than those in
      the land exercise (P < 0.01) and control (P < 0.05) groups. CONCLUSION: Land
      exercise produced a greater decrease in body fat and an increase in lean body
      mass, whereas water exercise was better for improving breast symptoms.

PMID- 22864471
TI  - Neuroprotective strategies in the prevention of chemotherapy-induced
      neuropathies.

PMID- 22864472
TI  - Nurse-led follow-up care for head and neck cancer patients: a quasi-experimental
      prospective trial.
AB  - PURPOSE: The aim of this study was to compare conventional medical follow-up with
      follow-up containing additional nursing consultations regarding the psychosocial
      adjustment and health-related quality of life (HRQOL) of head and neck cancer
      patients. METHODS: Using a quasi-experimental design, patients were enrolled
      consecutively into two groups. Experimental care covered six 30-min bimonthly
      nursing follow-up consultations during the first year posttreatment. Data were
      collected at posttreatment months 1 (baseline), 6, and 12 for both groups.
      RESULTS: The intervention group was significantly worse at baseline, based on two
      of the seven adjustment scales and on the majority of HRQOL scales. However,
      their outcome at 6 and 12 months was consistent with that of the group which
      received conventional follow-up. Thus, the intervention group had a larger
      improvement in scores, and this was significant for one of the seven adjustment
      scales and 19 of the 33 HRQOL scales at 6 and 12 months, respectively. Most of
      the differences in HRQOL scales were clinically relevant at 6 months. CONCLUSION:
      These results suggest that nurse-led consultations for patients with head and
      neck cancer have a positive effect, primarily with respect to HRQOL. Nurse-led
      follow-up leads to a similar psychosocial adjustment as conventional follow-up,
      even among patients who showed worse performance at the start of follow-up. Thus,
      nurse-led follow-up may be a cost-effective way to improve follow-up care for
      this patient group.

PMID- 22864473
TI  - Peripherally inserted central catheters (PICCs) in the management of
      oncohematological patients submitted to autologous stem cell transplantation.
AB  - The aim of our study was to evaluate the feasibility and the safety of the use of
      peripherally inserted central catheters (PICCs) during autologous peripheral
      blood stem cell transplantation. Sixty PICCs were inserted in 57 patients (23
      females and 34 males; mean age 48, range 19-68 years) and remained in place for
      an overall period of 1,276 days. All PICCs were positioned by a team of
      specifically trained physicians and nurses and utilized by specifically trained
      nurses of our hematology unit. No major insertion-related complications were
      observed; the only complication during insertion was one local hematoma (1.6 %)
      due to accidental arterial puncture. Late complications were accidental catheter
      removal (5 %, 2.3 per 1,000 PICC days), symptomatic catheter-related venous
      thrombosis (5 %, 2.3 per 1,000 PICC days), and catheter-related bloodstream
      infection (CRBSI; 3.3 %, 1.5 CRBSI per 1,000 PICC days). The reasons for catheter
      removal were completion of therapy (42 patients, 70 %), fever of unknown origin
      (9 patients, 15 %), catheter-related thrombosis (2 patients, 3.3 %), CRBSI (2
      patients, 3.3 %), accidental removal (3 patients, 5 %), lumen occlusion (1
      patient, 1.6 %), positive culture from peripheral blood (1 patient, 1.6 %), and
      death (1 patient, 1.6 %). Our data suggest that PICCs are a safe and effective
      alternative to conventional central venous catheters even in patients
      particularly prone to infective and hemorrhagic complications such as patients
      receiving autologous stem cell transplantation.

PMID- 22864474
TI  - Relationships between carapace sizes and plasma major and trace element status in
      captive hawksbill sea turtles (Eretmochelys imbricata).
AB  - The aim of this study was to evaluate the relationships between carapace
      parameters as indicators of age and plasma elements in 25 captive hawksbill sea
      turtles. Particle-induced X-ray emission allowed detection of 23 trace and major
      elements. There were significant but weak correlations between the virtual
      carapace surface area and plasma bromide (r = -0.552, P<0.01), phosphorus (r =
      0.547, P<0.01), lead (r =-0.434, P<0.05) and strontium (r = 0.599, P<0.01), while
      there were no significant correlations with other elements. These results suggest
      that major and trace plasma elements in captive sea turtles show almost no
      variation with carapace parameters, suggesting that the increase in plasma
      elements seen in wild sea turtles might be the result of marine pollution.

PMID- 22864475
TI  - Drop formation in non-planar microfluidic devices.
AB  - Microfluidic devices can be used to produce single or multiple emulsions with
      remarkably precise control of both the contents and size of the drops. Since each
      level of a multiple emulsion is formed by a distinct fluid stream, very efficient
      encapsulation of materials can be achieved. To obtain high throughput, these
      devices can be fabricated lithographically, allowing many devices to operate in
      parallel. However, to form multiple emulsions using a planar microfluidic device,
      the wettability of its surface must switch from hydrophobic to hydrophilic on the
      scale of micrometers where the drops are formed; this makes the fabrication of
      the devices very difficult. To overcome this constraint, we introduce non-planar
      microfluidic devices with graduated thicknesses; these can make drops even when
      their wetting properties do not favor drop formation. Nevertheless, the
      dependence of drop formation on the device geometry, the flow rates and the
      properties of the fluids, particularly in the case of unfavorable wetting, is
      very complex, making the successful design of these devices more difficult. Here
      we show that there exists a critical value of flow of the continuous phase above
      which drop formation occurs; this value decreases by two orders of magnitude as
      the wetting to the device wall of the continuous phase improves. We demonstrate
      how this new understanding can be used to optimize device design for efficient
      production of double or multiple emulsions.

PMID- 22864476
TI  - Effective and selective extraction of noble metal nanoparticles from
      environmental water through a noncovalent reversible reaction on an ionic
      exchange resin.
AB  - Capable of preserving the size and shape of nanoparticles, a novel method to
      effectively and selectively extract noble metal nanoparticles even at the 80 ng
      L(-1) level from real environmental water was designed and performed using a
      noncovalent reversible adsorption onto an ionic exchange resin.

PMID- 22864477
TI  - Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors
      suppresses retinoblastoma formation.
AB  - Synthetic lethality is a promising strategy for specific targeting of cancer
      cells that carry mutations that are absent in normal cells. This approach may
      help overcome the challenge associated with targeting dysfunctional tumour
      suppressors, such as p53 and Rb (refs 1, 2). Here we show that Dicer1 targeting
      prevents retinoblastoma formation in mice by synthetic lethality with combined
      inactivation of p53 and Rb. Although Dicer1 functions as a haploinsufficient
      tumour suppressor, its complete loss of function is selected against during
      tumorigenesis(3-5). We show that Dicer1 deficiency is tolerated in Rb-deficient
      retinal progenitor cells harbouring an intact p53 pathway, but not in the absence
      of p53. This synthetic lethality is mediated by the oncogenic miR-17-92 cluster
      because its deletion phenocopies Dicer1 loss in this context. miR-17-92
      inactivation suppresses retinoblastoma formation in mice and co-silencing of miR
      17/20a and p53 cooperatively decreases the viability of human retinoblastoma
      cells. These data provide an explanation for the selective pressure against loss
      of Dicer1 during tumorigenesis and a proof-of-concept that targeting miRNAs may
      potentially represent a general approach for synthetic lethal targeting of cancer
      cells that harbour specific cancer-inducing genotypes.

PMID- 22864480
TI  - Foreword from Director of the National Institute on Minority Health and Health
      Disparities (NIMHD), National Institutes of Health (NIH).

PMID- 22864478
TI  - 2nd PEGS Annual Symposium on Antibodies for Cancer Therapy: April 30-May 1, 2012,
      Boston, USA.
AB  - The 2nd Annual Antibodies for Cancer Therapy symposium, organized again by
      Cambridge Healthtech Institute as part of the Protein Engineering Summit, was
      held in Boston, USA from April 30th to May 1st, 2012. Since the approval of the
      first cancer antibody therapeutic, rituximab, fifteen years ago, eleven have been
      approved for cancer therapy, although one, gemtuzumab ozogamicin, was withdrawn
      from the market. The first day of the symposium started with a historical review
      of early work for lymphomas and leukemias and the evolution from murine to human
      antibodies. The symposium discussed the current status and future perspectives of
      therapeutic antibodies in the biology of immunoglobulin, emerging research on
      biosimilars and biobetters, and engineering bispecific antibodies and antibody
      drug conjugates. The tumor penetration session was focused on the understanding
      of antibody therapy using ex vivo tumor spheroids and the development of novel
      agents targeting epithelial junctions in solid tumors. The second day of the
      symposium discussed the development of new generation recombinant immunotoxins
      with low immunogenicity, construction of chimeric antigen receptors, and the
      proof-of-concept of 'photoimmunotherapy'. The preclinical and clinical session
      presented antibodies targeting Notch signaling and chemokine receptors. Finally,
      the symposium discussed emerging technologies and platforms for therapeutic
      antibody discovery.

PMID- 22864479
TI  - Destabilizing giant vesicles with electric fields: an overview of current
      applications.
AB  - This review presents an overview of the effects of electric fields on giant
      unilamellar vesicles. The application of electrical fields leads to three basic
      phenomena: shape changes, membrane breakdown, and uptake of molecules. We
      describe how some of these observations can be used to measure a variety of
      physical properties of lipid membranes or to advance our understanding of the
      phenomena of electropermeabilization. We also present results on how
      electropermeabilization and other liposome responses to applied fields are
      affected by lipid composition and by the presence of molecules of therapeutic
      interest in the surrounding solution.

PMID- 22864481
TI  - Foreword from Associate Administrators of the Health Resources and Services
      Administration (HRSA), U.S. Department of Health and Human Services.

PMID- 22864482
TI  - HRSA and NIH guest editors' preface.

PMID- 22864483
TI  - Progress toward reaching better health and providing more affordable care for
      vulnerable populations.

PMID- 22864484
TI  - Redesigning the system from the bottom up: lessons learned from a decade of
      federal quality improvement collaboratives.
AB  - The Health Resources and Services Administration (HRSA) is a federal agency that
      provides support and resources for America's safety-net providers. For more than
      10 years, HRSA has engaged in Quality Improvement Breakthrough Collaboratives
      that have brought together multiple stakeholders to improve quality of care and
      enhance patient outcomes for the most vulnerable populations. Many of these
      collaboratives followed the Institute for Healthcare Improvement's Breakthrough
      Series Collaborative model and methodology to implement small tests of change
      that helped generate process improvements and clinical outcomes. This commentary
      summarizes HRSA's experience with these Quality Improvement Breakthrough
      Collaboratives, focusing on key lessons learned, in order to help inform and
      enhance future quality improvement efforts in both the public and the private
      sectors.

PMID- 22864485
TI  - The Healthy Weight Collaborative: quality improvement methods promoting healthy
      weight.
AB  - Promoting healthy weight requires innovative approaches and a concerted response
      across all sectors of society. This commentary features the framework guiding the
      Healthy Weight Collaborative, a two-phased quality improvement (QI) learning
      collaborative and key activity of the Collaborate for Healthy Weight initiative.
      Multi-sector teams from primary care, public health, and community-based
      organizations use QI to identify, test, and implement program and policy changes
      in their communities related to promoting healthy weight. We describe the
      Collaborative's overall design based on the Action Model to Achieve Healthy
      People 2020 Goals and our approach of applying QI methods to advance
      implementation of sustainable ways to promote healthy weight and healthy equity.
      We provide specifics on measurement and change strategies as well as examples of
      Plan-Do-Study-Act cycles from teams participating in Phase 1 of the
      Collaborative. These teams will serve as leaders for sustainable, positive change
      in their communities.

PMID- 22864486
TI  - Hemoglobinopathy Learning Collaborative: using quality improvement (QI) to
      achieve equity in health care quality, coordination, and outcomes for sickle cell
      disease.
AB  - Care and outcomes for individuals living with sickle cell disease (SCD) vary
      across institutions and communities. The Hemoglobinopathy Learning Collaborative
      (HLC) seeks to improve outcomes across the life course through improvement
      science. Faculty identified five key drivers of improved outcomes: a strong
      community network; knowledgeable, proactive individuals, families and providers;
      reliable identification and follow-up; seamless co-management between primary and
      specialty care; and appropriate treatment for acute episodes. Using a modified
      Delphi process, we selected improvement measures aligned with the drivers. Data
      are collected via a Web-based system linked to a reporting portal. Participating
      teams include consumers, community organizations and primary and specialty care
      providers. This commentary reviews the context of SCD in the U.S.; describes the
      framework, measures, and technology infrastructure already created for the HLC;
      reports on the early experience of teams; highlights the initiative's challenges
      and opportunities; and reflects on its implications in the setting of health
      reform.

PMID- 22864487
TI  - Chronic Care Model implementation for cancer screening and follow-up in community
      health centers.
AB  - BACKGROUND: The Health Disparities Cancer Collaborative (HDCC) implemented six
      components of the Chronic Care Model (CCM) to increase cancer screening and
      follow-up among underserved populations from 2003-05. METHODS: Organizational
      surveys were administered among 19 community health centers participating in the
      HDCC and 22 matched control centers. Health care providers, directors, financial
      officers, information systems personnel, and general staff completed surveys to
      measure CCM implementation (primary outcome) and cancer care process improvement
      (secondary outcome) at the organizational level. RESULTS: The HDCC community
      health centers were more likely to report CCM implementation than control
      centers. The HDCC and control centers were equally likely to report cancer care
      process improvement, but CCM implementation was significantly associated with
      process improvement in adjusted models. CONCLUSIONS: Implementation of CCM, not
      solely HDCC participation, was associated with cancer care process improvement.
      Organizational and individual change is challenging among the large, healthy
      populations eligible for cancer screening.

PMID- 22864488
TI  - Improved quality of HIV care over time among participants in a national quality
      improvement initiative.
AB  - Ensuring comprehensive quality HIV and primary care is critical for effective HIV
      management. This study evaluates the impact of long-term engagement in a quality
      management (QM) initiative on performance measures. HIVQUAL-US is a federally
      funded program to build clinic QM capacity to improve care for people living with
      HIV/AIDS. Forty-five facilities with four or more years of HIVQUAL-US performance
      measurement between 2002 and 2009 were included. Composite quality scores were
      constructed for HIV care, primary care and overall quality. Unadjusted analyses
      showed significant improvements in HIV care (76.2% to 88.8%, p<.0001), primary
      care (65.7% to 71.4%, p<.05) and overall (70.6% to 79.6%, p<.0001). Improvement
      was higher among clinics performing in the lowest quartile. Adjusting for clinic
      factors, the probability of improvement increased with each additional year of
      data submission for all scores. Engagement in a QM capacity building program was
      associated with continuing improvement in quality of HIV and primary care.

PMID- 22864489
TI  - Retention: building a patient-centered medical home in HIV primary care through
      PUFF (Patients Unable to Follow-up Found).
AB  - Here, we describe our patient-centered medical home (PCMH) quality improvement
      retention project conducted by a Health Resources and Services Administration
      (HRSA) Ryan White-funded Primary Care HIV clinic. The single urban academic
      clinic serving 2,776 active HIV positive patients identified 25.8% (716/2,776)
      patients who had not been retained in care within the prior six months during two
      separate six-month interval analyses. Multiple modalities including a retention
      specialist, a secure clinic phone message line, algorithms, flyers, brochures,
      database, and staff education were built to facilitate re-engagement. The project
      located 87.7% (628/716) patients who had not been retained. The retention
      specialist was directly responsible for the return of 16.2% (116/716) patients.
      Results from the project demonstrated that a formalized approach is a necessary
      component to effective retention efforts. We believe that this work will provide
      a strategic framework for the development of randomized control trials to
      formally evaluate an HIV retention intervention.

PMID- 22864490
TI  - The Patient Safety and Clinical Pharmacy Collaborative: improving medication use
      systems for the underserved.
AB  - The Patient Safety and Clinical Pharmacy Services Collaborative (PSPC) is
      demonstrating improvements in the quality of care delivered by safety-net
      organizations through integration of clinical pharmacy services. This article
      describes how the PSPC is leading meaningful change in the arena of medication
      use in management of chronic disease.

PMID- 22864491
TI  - Urban health and primary care at Johns Hopkins: urban primary care medical home
      resident training programs.
AB  - Johns Hopkins University recently implemented two novel urban health residency
      training programs (UHR). The programs include increased access programs,
      community health worker-delivered care, substance abuse screening and treatment,
      community psychiatry/ mental health programs, case and disease management teams,
      and interprofessional training. These programs are designed to create well
      trained physicians who competently provide care for the underserved inner-city
      patient.

PMID- 22864492
TI  - Interprofessional collaborative model for medication therapy management (MTM)
      services to improve health care access and quality for underserved populations.
AB  - As part of the Health Resources and Services Administration Patient Safety and
      Clinical Pharmacy Services Collaborative (PSPC), an interprofessional model with
      medication therapy management documentation and outcomes tracking tools (MTM
      DOTT) is established to improve health care access and quality for underserved
      populations. Despite limitations, there have been positive outcomes and national
      recognitions.

PMID- 22864493
TI  - Geographic proximity of HRSA, VA, and DOD clinics: opportunities for interagency
      collaboration to improve quality.
AB  - Clinics funded by the Department of Veterans Affairs (VA), Department of
      Defense's Military Health System (MHS), and Department of Health and Human
      Services' Health Resources and Services Administration (HRSA) all play a role in
      serving the military, veterans, and their families. Publicly available location
      data on federal health care clinics was merged, analyzed, and geographically
      overlaid using GIS. Results showed that 20% of U.S. counties contain both HRSA
      and VA sites, and 5% contain HRSA and MHS facilities. Additionally, 80% of VA and
      76% of MHS clinics are within 10 miles of a HRSA clinic. Specific clinic types of
      interest also overlay; for instance, 90% of HRSA homeless clinics are in the same
      county as a VA facility. This demonstrated geographic proximity of health care
      sites may indicate prime opportunities for collaboration between HRSA, VA, and
      MHS systems to improve quality of care for the military, veterans, and their
      families.

PMID- 22864494
TI  - Electronic health records improve the quality of care in underserved populations:
      a literature review.
AB  - Organizations in underserved settings are implementing or upgrading electronic
      health records (EHRs) in hopes of improving quality and meeting Federal goals for
      meaningful use of EHRs. However, much of the research that has been conducted on
      health information technology does not study use in underserved settings, or does
      not include EHRs. We conducted a structured literature search of MEDLINE to find
      articles supporting the contention that EHRs improve quality in underserved
      settings. We found 17 articles published between 2003 and 2011. These articles
      were mostly in urban settings, and most study types were descriptive in nature.
      The articles provide evidence that EHRs can improve documentation, process
      measures, guideline-adherence, and (to a lesser extent) outcome measures.
      Providers and managers believed that EHRs would improve the quality and
      efficiency of care. The limited quantity and quality of evidence point to a need
      for ongoing research in this area.

PMID- 22864495
TI  - Improving care for depression: performance measures, outcomes and insights from
      the Health Disparities Collaboratives.
AB  - This paper reports 10 measures, outcomes, and insights from HRSA Depression
      Health Disparities Collaboratives, representing attempts to accelerate evidence
      based guidelines into practice. The authors analyze interviews with leadership of
      high-performing centers. Monthly data was submitted on 38,000 patients from 94
      centers. Regression analyses were conducted to identify process measures
      predictive of better outcomes. Results indicated that these 10 measures of care
      were effective in guiding and quantifying improved outcomes. One measure, early
      and sustained response (ESR), proved particularly useful as it reflects long term
      outcomes. Regression analyses identified one process measure (Patient Health
      Questionnaire Reassessment) strongly associated with improved clinical outcomes
      (n=37, R2=44%). Interviews identified 18 process changes deemed pivotal for
      meaningful change. In sum, well-designed approaches utilizing proven improvement
      methodologies resulted in substantial enhancements in depression care. This
      approach and these measures, especially ESR and PHQ Reassessment, may improve
      depression care in other under-served settings.

PMID- 22864496
TI  - Evaluation of regional HIV provider quality groups to improve care for people
      living with HIV served in the United States.
AB  - HIVQUAL-US is a capacity-building quality initiative for federally-funded HIV
      primary care clinics. Since 2004, HIVQUAL-US has supported the formation of
      regional groups, geographically-clustered clinics that build quality management
      capacity through collective learning about quality improvement. The purpose of
      this qualitative study was to examine members' experiences participating in
      groups and their self-reported quality management and improvement outcomes
      related to HIV primary care. Interviews were conducted with a sample of three
      HIVQUAL-US coaches who facilitated 11 regional groups and with nine of the clinic
      representatives participating in the regional groups. The regional groups were
      heterogeneous in composition, focus and style, but shared common activities.
      Benefits included implementation of group quality improvement projects and
      opportunities for sharing activities and challenges. Improved performance in
      targeted areas, enhanced understanding/use of improvement methods, and increased
      quality management capacity were reported outcomes. Regional groups can
      effectively promote peer-to-peer learning, develop leadership, strengthen quality
      management capacity, and improve quality of care for the HIV population.

PMID- 22864497
TI  - Disease management of early childhood caries: results of a pilot quality
      improvement project.
AB  - OBJECTIVES: The purpose is to report findings of a quality improvement (QI)
      project implemented at two hospital-based dental clinics that care for children
      with early childhood caries (ECC). METHODS: We tested a disease management (DM)
      approach in children younger than age 60 months with ECC. RESULTS: After 30
      months, for the 403 and 234 DM patients at Children's Hospital Boston (CHB) and
      Saint Joseph Hospital (SJH) who returned for at least two visits, rates of new
      cavitation, pain, and referrals to the OR were 26.1, 13.4 and 10.9% for CHB and
      41.0, 7.3 and 14.9% for SJH. Rates of new cavitation, pain, and referrals to the
      OR for historical controls were 75.2, 21.7, and 20.9% for CHB and 71.3, 31.3, and
      25.0% for SJH. CONCLUSIONS: A risk-based DM approach utilizing QI strategies to
      address ECC can be implemented into practice and has the potential to improve
      care and health outcomes.

PMID- 22864498
TI  - Lessons learned from a quality improvement intervention with homeless veteran
      services.
AB  - Homeless veterans are a vulnerable population, with high mortality and morbidity
      rates. Evidence-based practices for homelessness have been challenging to
      implement. This study engaged staff members from three VA homeless programs to
      improve their quality using Getting-To-Outcomes (GTO), a model and intervention
      of trainings and technical assistance that builds practitioner capacity to plan,
      implement, and self-evaluate evidence-based practices. Primarily used in
      community-based, non-VA settings, this study piloted GTO in VA by creating a GTO
      project within each homeless program and one across all three. The feasibility
      and acceptability of GTO in VA is examined using the results of the projects,
      time spent on GTO, and data from focus groups and interviews. With staff members
      averaging 33 minutes per week on GTO, each team made significant programmatic
      changes. Homeless staff stated GTO was helpful, and that high levels of
      communication, staff member commitment to the program, and technical assistance
      were critical.

PMID- 22864499
TI  - National performance measures within a changing environment: how a federal agency
      developed and improved the measurement for HIV care and treatment.
AB  - The United States Department of Health and Human Services (HHS) must ensure that
      access to high quality care is provided through the Ryan White HIV/AIDS Program
      (RWP). The RWP is committed to improving the quality of care and services to
      reduce mortality and improve quality of life for people living with HIV. This
      commitment is evidenced by the comprehensive range of efforts taken by the HHS,
      Health Resources and Services Administration (HRSA), HIV/AIDS Bureau (HAB) to
      address the quality of care, treatment and other services across all programs
      funded by the RWP. To assure high quality care, HRSA/HAB engages in many quality
      initiatives, with the development of performance measures as a central core of
      its overall activities. The HRSA/HAB defined a solid foundation for the measures
      development process, which has been refined over time, facilitating the timely
      release and use of performance measures by the HIV service provider community.

PMID- 22864500
TI  - Collaborative development of a randomized study to adapt a diabetes quality
      improvement initiative for federally qualified health centers.
AB  - This case study describes how we are translating a diabetes care quality
      improvement initiative from an insured (HMO) setting into federally qualified
      health centers (FQHCs). We outline the innovative collaborative processes whereby
      researchers and FQHC providers adapted this initiative, which includes health
      information technology tools, to meet the FQHCs' needs.

PMID- 22864501
TI  - Preventing diabetes among Fair Haven families: a community-based approach to
      quality improvement.
AB  - In this paper, we describe our efforts to integrate the Diabetes Prevention
      Program and the Bright Bodies program into a coordinated intensive lifestyle
      intervention program for families living in Fair Haven, an underserved Hispanic
      neighborhood in New Haven, Connecticut with high rates of obesity and prediabetes
      in adults and children.

PMID- 22864502
TI  - An investigation of asthma care best practices in a community health center.
AB  - Urban Health Plan, Inc. (UHP) implemented a comprehensive asthma management
      program that has resulted in sustained improvements in patient outcomes for UHP's
      primarily Latino and Black populations in the South Bronx. UHP is now engaged in
      a community-academic partnership to build community research capacity from its
      strength in quality improvement.

PMID- 22864503
TI  - Safe sobering: San Francisco's approach to chronic public inebriation.
AB  - Dedicated to the care of alcohol dependent people, the San Francisco Sobering
      Center cares for intoxicated clients historically treated via emergency services.
      With 29,000 encounters and 8,100 unduplicated clients, the Sobering Center safely
      and efficiently provides sobering and health care services to some of the City's
      most vulnerable people.

PMID- 22864504
TI  - Preparation of core-shell poly(L-lactic) acid-nanocrystalline apatite hollow
      microspheres for bone repairing applications.
AB  - In this paper, hybrid inorganic-organic core-shell hollow microspheres, made of
      poly(L-lactic acid) (PLLA) and biomimetic nano apatites (HA), were prepared from
      biodegradable and biocompatible substances, suitable for bone tissue
      applications. Preparation is started from Pickering emulsification, i.e., solid
      particle-stabilized emulsions in the absence of any molecular surfactant, where
      solid particles adsorbed to an oil-water interface. Stable oil-in-water emulsions
      were produced using biomimetic 20 nm sized HA nanocrystals as particulate
      emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLLA as oil phase.
      Hybrid hollow PLLA microspheres at three different HA nanocrystals surface
      coverage, ranging from 10 to 50 MUm, were produced. The resulting materials were
      completely characterized with spectroscopic, calorimetric and microscopic
      techniques and the cytocompatibility was established by indirect contact tests
      with both fibroblasts and osteoblasts and direct contact with these latter. They
      displayed a high level of cytocompatibility and thus represent promising
      materials for drug delivery systems, cell carriers and scaffolds for regeneration
      of bone useful in the treatment of orthopaedic, maxillofacial and dental fields.

PMID- 22864505
TI  - Cloning, expression and characterization of a novel salt-tolerant xylanase from
      Bacillus sp. SN5.
AB  - A xylanase gene (xyn10A) was cloned from Bacillus sp. SN5 and expressed in
      Escherichia coli. It encoded a 348-residue polypeptide of ~45 kDa. The deduced
      amino acid sequence had 68 % identity with the endo-1,4-beta-xylanase from
      Paenibacillus lactis 154 that belonged to family 10 of the glycoside hydrolases.
      Purified recombinant Xyn10A had maximum activity at 40  degrees C and pH 7.0,
      with the specific activity of 105 U/mg and a Km of 0.6 mg/ml for beechwood xylan.
      Xyn10A retained more than 80 % activity between 25 and 45  degrees C and 29 %
      activity at 5  degrees C. It exhibited the highest activity (134 %) in 0.5 M NaCl
      and still retained 90 % activity in 2.5 M NaCl. It retained about 87 % activity
      after incubation in 2 M NaCl for 24 h. The cold-active and halo-tolerant
      properties of Xyn10A make it promising for application in the food industry,
      especially in the processing of saline food and sea food.

PMID- 22864506
TI  - Protective effect of whey protein hydrolysates against hydrogen peroxide-induced
      oxidative stress on PC12 cells.
AB  - The protective effect of whey protein hydrolysates (WPHs) against H(2)O(2)
      induced oxidative damage on rat pheochromocytoma line 12 (PC12) cells was
      studied. Whey protein was hydrolyzed by pepsin and trypsin and purified by
      macrospore absorption resins. PC12 cells were pretreated with WPHs (from 369 to
      1,980 Da) at different concentrations for 2 h, then washed and incubated with 100
      MUM H(2)O(2) in the presence of WPHs for another 24 h. With 100-400 MUg WPH/ml
      the viable cells increased by 20-30 % when incubated with H(2)O(2) suggesting
      that they may play a role as antioxidant in foods.

PMID- 22864507
TI  - Serious fall injuries in hospitalized patients with and without cancer.
AB  - Characteristics of adults hospitalized with and without cancer were compared to
      determine factors of serious injuries after fall events. More patients with
      cancer who had a serious injury received corticosteroids (P = .005) and were
      treated on a palliative care floor. More patients without cancer had higher
      prevalence of stroke (P = .026) and diabetes (P = .041) history and were treated
      on a surgical floor. Future research is needed to identify interventions that
      could prevent serious injuries after fall events.

PMID- 22864508
TI  - Pediatric head injuries from earthquakes.
AB  - By means of some illustrations, the authors briefly report the effects of some
      accidental head injuries caused by diverse mechanisms occurring in children. Many
      of these accidents seem to be preventable, but others are completely unavoidable
      and escape prevention as the one that is depicted in the cover of this issue.

PMID- 22864509
TI  - Pediatric focal intracranial suppuration: a UK single-center experience.
AB  - PURPOSE: Brain abscess (BA) and subdural empyema (SDE) are uncommon but
      clinically important conditions in childhood. Treatment involves surgery and
      prolonged courses of antibiotics. There is no consensus on the optimal approach.
      The objective was to review management and outcome of BA and SDE in a single UK
      center. METHODS: This retrospective case notes review of children with brain
      abscess or subdural empyema admitted to a tertiary pediatric infectious diseases
      and neurosurgical center from 2001 to 2009. RESULTS: Forty-two children were
      included in the study; 17 children were with BA, 23 with SDE, and two both with
      BA and SDE. The causative factors found in 88 % of the patients were most
      commonly sinusitis and meningitis with congenital heart disease and
      immunocompromise unusual. Streptococcus anginosus group organisms were most
      common; 10 % of the children had a resistant pathogen and 86 % had surgical
      intervention. Fifteen patients with BA underwent surgery; nine of these patients
      underwent burrhole aspiration, three had craniotomy, two had stereotactic
      surgery, and one had endoscopic aspiration. Remaining 19 patients with SDE
      underwent surgery: seven had burrhole aspiration, 11 underwent craniotomy, and
      one had aspiration via the anterior fontanel. The most common antibiotic regime
      was cefotaxime, metronidazole, and amoxicillin. Mean duration of treatment was
      14.4 weeks. Mean time until normalization of C reactive protein was 23 days.
      Survival was 95 % and 20 % had ongoing neurological sequelae. CONCLUSIONS: BA and
      SDE remain important childhood infections in the UK. Antibiotics are essential in
      the management of these cases. Empiric antibiotic choices require knowledge of
      likely pathogens and local resistance. Selected infections can be treated without
      surgical intervention. Long courses of antibiotics were administered. Outcome is
      good, and neurological sequelae were less common than found in previous series.

PMID- 22864510
TI  - Comparison of the efficacy of laterally wedged insoles and bespoke unloader knee
      orthoses in treating medial compartment knee osteoarthritis.
AB  - BACKGROUND: Patients suffering from medial compartment knee osteoarthritis (OA)
      may be treated with unloader knee orthoses or laterally wedged insoles.
      OBJECTIVES: The aim of this study was to identify and compare the effects of them
      on the gait parameters and pain in these patients. STUDY DESIGN: Quasi
      experimental. METHODS: Volunteer subjects with medial compartment knee OA (n =
      24, mean age 59.29 +/- 2.23 years) were randomly assigned to two separate groups
      and evaluated when wearing an unloader knee orthosis or insoles incorporating a 6
      degrees  lateral wedge. Testing was performed at baseline and after six weeks of
      each orthosis use. A visual analog scale score was used to assess pain and gait
      analysis was utilized to determine gait parameters. RESULTS: Both orthoses
      improved all parameters compared to the baseline condition (p = 0.000). However,
      no significant differences in pain (p = 0.649), adduction moment (p = 0.205),
      speed of walking (p = 0. 056) or step length (p = 0.687) were demonstrated
      between them. The knee range of motion (p = 0.000) were significantly different
      between the two interventions. CONCLUSION: Both orthoses reduced knee pain.
      Maximum knee range of motion was increased by both interventions although it was
      3 degrees less when wearing the knee orthosis. Clinical relevance Both orthoses
      reduce pain and improve gait anomalies in medial compartment knee OA. Our results
      suggest a laterally wedged insole can be an alternative conservative approach to
      unloader knee orthosis for treating symptoms of medial compartment knee OA.

PMID- 22864511
TI  - Two-step emulsification process for water-in-oil-in-water multiple emulsions
      stabilized by lamellar liquid crystals.
AB  - Multiple emulsions, also called complex emulsions or multiphase emulsions,
      include water-in-oil-in-water (W/O/W)-type and oil-in-water-in-oil (O/W/O)-type
      emulsions. W/O/W-type multiple emulsions, obtained by utilizing lamellar liquid
      crystal with a layer structure showing optical anisotropy at the periphery of
      emulsion droplets, are superior in stability to O/W/O-type emulsions. In this
      study, we investigated a two-step emulsification process for a W/O/W-type
      multiple emulsion utilizing liquid crystal emulsification. We found that a W/O/W
      type multiple emulsion containing lamellar liquid crystal can be prepared by
      mixing a W/O-type emulsion (prepared by primary emulsification) with a lamellar
      liquid crystal obtained from poly(oxyethylene) stearyl ether, cetyl alcohol, and
      water, and by dispersing and emulsifying the mixture in an outer aqueous phase.
      When poly(oxyethylene) stearyl ether and cetyl alcohol are each used in a given
      amount and the amount of water added is varied from 0 to 15 g (total amount of
      emulsion, 100 g), a W/O/W-type multiple emulsion is efficiently prepared. When
      the W/O/W-type multiple emulsion was held in a thermostatic bath at 25 degrees C,
      the droplet size distribution showed no change 0, 30, or 60 days after
      preparation. Moreover, the W/O/W-type multiple emulsion strongly encapsulated
      Uranine in the inner aqueous phase as compared with emulsions prepared by one
      step emulsification.

PMID- 22864512
TI  - Gas chromatographic separation of docosenoic acid positional isomers on an SLB
      IL100 ionic liquid column.
AB  - Gas chromatography (GC) of docosenoic acid (22:1) has been performed for the
      separation of positional isomers on the novel SLB-IL100 column with a highly
      polar ionic liquid stationary phase. A test mixture of 22:1 methyl esters
      prepared from total lipids of flounder was subjected to GC on a 60 m*0.32 mm i.d.
      column at an isothermal temperature of 150 degrees C-180 degrees C. On this
      column, all five positional isomers separated in the elution order of 22:1n-15,
      22:1n-13, 22:1n-11, 22:1n-9, and 22:1n-7. The positional isomers, 22:1n-15, 22:1n
      13, and 22:1n-11, unresolvable on conventional polar polymer phase columns, were
      almost completely separated from each other within 24 min at 170 degrees C. The
      equivalent chain length values of 22:1n-11 to 22:1n-7 were parallel to those on
      polyethylene glycol and cyanopropyl polysiloxane columns, whereas 22:1n-15 and
      22:1n-13 were relatively lower and closer to saturated 22:0 acid. Similar
      findings were also obtained for co-injected 20:1n-15 to 20:1n-11 isomers.
      Analysis of fish 22:1 revealed that 22:1n-13 is not always a minor isomer, as
      previously reported for several samples. The results of this study confirm the
      view that SLB-IL100 is a powerful tool for GC analysis of monounsaturated fatty
      acids.

PMID- 22864513
TI  - Docosahexaenoic- and eicosapentaenoic acid-bound lysophospholipids are more
      effective in suppressing angiogenesis than conjugated docosahexaenoic acid.
AB  - Suppression of leukemia, colon cancer, myeloma, and fibrosarcoma to some extent
      by omega 3 fatty acid bound phospholipids has been reported in the last two
      decade. However, the anti-angiogenic activity of those phospholipids is still not
      known. Four kinds of marine phospholipid molecular species i.e. starfish EPA
      bound diacyl phospholipid (EPA-PC), EPA bound monoacyl phospholipid (EPA-LPC)
      which was prepare via Lipozyme RMIM mediated partial hydrolysis of EPA-PC, squid
      DHA bound diacyl phospholipid (DHA-PC), and DHA bound monoacyl phospholipid (DHA
      LPC) which was also prepare via Lipozyme RMIM mediated partial hydrolysis of DHA
      PC, were subjected to antiangiogenic activity assay by using a piece of rat main
      artery and a human umbilical cord vein endothelial cell. The lengths of micro
      vein generated from those tissues after incubation with the above four kinds of
      phospholipid molecular species were measured and compared. EPA-LPC and DHA-LPC
      showed strong antiangiogenic activity on the rat main artery tissue, while on the
      human umbilical cord vein endothelial cells, 100 uM of EPA-LPC in the culture
      medium, exhibited the most effective suppression on angiogenesis, followed by 100
      uM of DHA-LPC. It was concluded that EPA-LPC obtained via Lipozyme RMIM mediated
      partial hydrolysis of EPA-PC is the most effective omega 3 phospholipid on anti
      angiogenesis.

PMID- 22864514
TI  - jacaric acid, a linolenic acid isomer with a conjugated triene system, reduces
      stearoyl-CoA desaturase expression in liver of mice.
AB  - Conjugated fatty acid is a collective term used for fatty acids with conjugated
      double bond systems. Seed oils from certain plants include conjugated linolenic
      acids, which have a conjugated triene system and are geometrical and positional
      isomers of alpha-linolenic acid. One of these isomers, jacaric acid (JA, 8c, 10t,
      12c-18:3), has not been examined widely. Therefore, we investigated the
      absorption and metabolism of JA in normal animals (ICR mice). An oral dose of JA
      of 5 mg/day for 1 week had no effects on body weight, food intake and tissue
      weight of mice. JA was detected in the serum, kidney, liver, lung and epididymal
      white adipose tissue. Analysis of the fatty acid composition in liver and white
      adipose tissue showed a tendency to increase levels of saturated fatty acids
      (SFAs) such as palmitic acid (16:0) and stearic acid (18:0) and to decrease
      levels of monounsaturated fatty acids (MUFAs) such as palmitoleic acid (16:1) and
      oleic acid (18:1). Thus, JA treatment decreased the desaturation index
      (16:1/16:0, 18:1/18:0) in liver and white adipose tissue. This index is used as
      an indicator of the activity of stearoyl coenzyme A desaturase (SCD), an
      endoplasmic reticulum enzyme that catalyzes the biosynthesis of MUFAs from SFAs.
      The change in this index indicates that JA inhibited SCD activity in ICR mice,
      and further experiments showed that JA also decreased the expression level of SCD
      1 mRNA. Inhibition of SCD activity may have anti-obesity and anti-diabetes
      effects, and therefore the findings in this study suggest that JA may be
      effective for preventing obesity and diabetes.

PMID- 22864515
TI  - Hydratase activities of green fluorescent protein tagged human multifunctional
      enzyme type 2 hydratase domain and its variants.
AB  - In order to clarify the physiological significance of stereospecificities of
      peroxisomal multifunctional enzyme (MFE) type 1 (MFE1) and MFE2, we developed a
      chiral separation analysis for 3-hydroxyacyl-CoA using high performance liquid
      chromatography (HPLC) equipped with a chiral separation column. To demonstrate
      the utility of this technique, we cloned the hydratase domain from wild-type
      human MFE2 hydratase (MFE2Hwt) and expressed it as a GFP-tagged protein (GFP
      MFE2Hwt) in Escherichia coli (E. coli). GFP-MFE2H was purified by
      diethylaminoethyl (DEAE) Sephacel from an E. coli sonication solution. As
      anticipated, we observed the formation of 3R-hydroxyhexadecanoyl-CoA (3R-OH-16
      CoA) on the HPLC chromatogram after incubating trans-2-enoyl-CoA (16eno-CoA) with
      GFP-MFE2Hwt. GFP-MFE2Hwt was readily purifiable and could be assayed because of
      its traceability. We used site-directed mutagenesis to construct GFP-MFE2H
      variants corresponding to 17 reported MFE2H missense mutations and measured their
      hydratase activities using our HPLC method. Hydratase activity was completely
      lost or markedly decreased in the same variants corresponding to MFE2H mutations
      in patients with D-bifunctional protein (DBP) deficiency type II. On the other
      hand, the nonpathological variants did not markedly affect hydratase activity.

PMID- 22864516
TI  - A 9 GHz EPR imager for thin materials: application to surface detection.
AB  - A 9 GHz EPR imager that is capable of the imaging surface area of thin materials
      has been built. The EPR imager resolved samples spaced 1 mm apart. The developed
      TE(111) cavity was able to detect easily ~1.0 mM aqueous TEMPOL solution in ~1.0
      mm (i.d.) glass capillary placed just above the cavity. The sensitivity measured
      using the TEMPOL solution showed ~0.3 of that for the modified JEOL cavity, which
      was in a qualitative agreement with the calculations considering the difference
      in the filling factors of the cavities. The relatively low measured sensitivity
      of the TE(111) cavity is due to utilization of the microwave field from ~3 mm
      aperture (hole) in the cavity wall. More importantly, the TE(111) cavity does not
      require inserting the sample into the cavity and placing samples into EPR tubes.

PMID- 22864517
TI  - Glycolipid biosurfactants, mannosylerythritol lipids, show antioxidant and
      protective effects against H(2)O(2)-induced oxidative stress in cultured human
      skin fibroblasts.
AB  - Mannosylerythritol lipids (MELs) are biosurfactants known for their versatile
      interfacial and biochemical properties. To broaden their application in
      cosmetics, we investigated the antioxidant properties of different MEL
      derivatives (MEL-A, -B, and -C) by using a 1,1-diphenyl-2-picryl hydrazine (DPPH)
      free-radical- and superoxide anion-scavenging assay. All MEL derivatives tested
      showed antioxidant activity in vitro, but at lower levels than those of arbutin.
      Of the MELs, MEL-C, which is produced from soybean oil by Pseudozyma hubeiensis,
      showed the highest rates of DPPH radical scavenging (50.3% at 10 mg/mL) and
      superoxide anion scavenging (>50% at 1 mg/mL). The antioxidant property of MEL-C
      was further examined using cultured human skin fibroblasts (NB1RGB cells) under
      H(2)O(2) induced oxidative stress. Surprisingly, MEL-C had a higher protective
      activity against oxidative stress than arbutin did: 10 ug/mL of MEL-C and arbutin
      had protective activities of 30.3% and 13%, respectively. Expression of an
      oxidative stress marker, cyclooxygenase-2, in these cells was repressed by
      treatment with MEL-C as well as by arbutin. MEL-C was thus confirmed to have
      antioxidant and protective effects in cells, and we suggest that MELs have
      potential as anti-aging skin care ingredients.

PMID- 22864518
TI  - Image of Erdheim-Chester disease requiring hemodialysis.

PMID- 22864519
TI  - Estimation of the nares-to-epiglottis distance and the nares-to-vocal cords
      distance in young children.
AB  - BACKGROUND: Estimation of the nares-to-epiglottis and nares-to-vocal cords
      distances would facilitate the selection of properly sized nasopharyngeal airways
      and appropriate positioning of a fibreoptic bronchoscope in young children. The
      purposes of this study were to measure the nares-to-epiglottis and nares-to-vocal
      cords distances and to create an algorithm to predict these distances based on
      anatomical landmarks and paediatric characteristic data. METHODS: Two hundred and
      eleven children, aged 1-10 yr, undergoing elective surgery were investigated.
      After induction of general anaesthesia, the distances from the nares to the
      epiglottis/vocal cords were measured using a nasogastric tube. After intubation,
      the distances from the lateral border of the nose to the ipsilateral mandible
      angle (nares-to-mandible distance) and the tragus of the ear (nares-to-tragus
      distance) were measured using a tape measure. RESULTS: The nares-to-epiglottis
      and nares-to-vocal cords distances were significantly correlated with the age,
      weight, height, and external measurements (P<0.001). By stepwise multiple linear
      regression analysis, formulas were obtained for the nares-to-epiglottis distance
      (cm)=2.606+0.058*height (cm)+0.231*the nares-to-mandible distance (cm)-0.304
      (gender) (r(2)=0.754) and for the nares-to-vocal cords distance
      (cm)=4.947+0.06*height (cm)+0.228*nares-to-mandible distance (cm)-0.283 (gender)
      (r(2)=0.803). CONCLUSIONS: The nares-to-epiglottis and nares-to-vocal cords
      distances can be predicted using the height and the nares-to-mandible distance in
      young children. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Research Information
      Service KCT0000150.

PMID- 22864520
TI  - Does motor block related to long-acting brachial plexus block cause patient
      dissatisfaction after minor wrist and hand surgery? A randomized observer-blinded
      trial.
AB  - BACKGROUND: Patient dissatisfaction has been previously associated with motor
      block in shoulder surgery patients receiving brachial plexus block. For elective
      minor wrist and hand surgery, we tested whether a regional block accelerating the
      early return of upper extremity motor function would improve patient satisfaction
      compared with a long-acting proximal brachial plexus block. METHODS: A total of
      177 patients having elective 'minor' wrist and hand surgery under awake regional
      block randomly received adrenalized infraclavicular lidocaine 2% 10
      ml+ropivacaine 0.75% 20 ml ('long acting', n=90), or adrenalized infraclavicular
      lidocaine 1.5% 30 ml+long-acting distal median, radial, and ulnar nerve blocks
      selected according to the anticipated area of postoperative pain ('short acting',
      n=87). A blinded observer questioned patients on day 1 for numerically rated (0
      10) subjective outcomes. RESULTS: With 95% power, there was no evidence for a 1
      point satisfaction shift in the short acting group: satisfaction was similarly
      high for both groups [median (inter-quartile range)=10 (8-10) vs 10 (8-10),
      P=0.71], and also demonstrated strong evidence for equivalence [mean difference
      (95% confidence interval)=-0.18 (-0.70 to 0.35)]. There was no difference between
      the groups for weakness- or numbness-related dissatisfaction (low for both
      groups), or for numerically rated or time to first pain. Surgical anaesthesia
      success was similar between the groups (short acting, 97% vs 93%, P=0.50),
      although more patients in the short acting group had surgery initiated in <=25
      min (P=0.03). CONCLUSIONS: Patient satisfaction is not improved after elective
      minor wrist and hand surgery with a regional block accelerating the early return
      of motor function. For this surgery, motor block related to a long-acting
      brachial plexus block does not appear to cause patient dissatisfaction. Clinical
      Trial Registration number. ACTRN12610000749000,
      https://www.anzctr.org.au/registry/trial_review.aspx?ID=335931.

PMID- 22864521
TI  - Synthesis and evaluation of oxovanadium(IV) complexes of Schiff-base condensates
      from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as
      selective inhibitors of protein tyrosine phosphatase 1B.
AB  - Five oxovanadium(IV) complexes, which were divided into two groups, [V(IV)O(bhbb,
      nhbb)(H(2)O)(2)] (tridentate ligands: H(2)bhbb = 2-(5-bromo-2
      hydroxylbenzylideneamino)benzoic acid, 1; H(2)nhbb = 2-(5-nitro-2
      hydroxylbenzylideneamino)benzoic acid, 2) and [V(IV)O(cpmp, bpmp, npmp)(2)]
      (bidentate ligands: Hcpmp = 4-chloro-2-((phenylimino)methyl)phenol, 3; Hbpmp = 4
      bromo-2-((phenylimino)methyl)phenol, 4; Hnpmp = 4-nitro-2-((phenylimino)methyl)
      phenol, 5) have been prepared and characterized by elemental analysis, infrared,
      UV-visible and electrospray ionization mass spectrometry. The coordination in
      [V(IV)O(bhbb)(H(2)O)(2)] (1) was confirmed by X-ray crystal structure analysis.
      The oxidation state of V(IV) with d(1) configuration in 1-5 was confirmed by EPR.
      The speciation of VO/H(2)bhbb in methanol-aqueous solution was investigated by
      potentiometric pH titrations. The result indicated that the main species were
      [V(IV)O(bhbb)(OH)](-) and [V(IV)O(bhbb)(OH)(2)](2-) at the pH range 7.0-7.4. The
      structure-activity relationship of the vanadium complexes in inhibiting protein
      tyrosine phosphatases (protein tyrosine phosphatase 1B, PTP1B; T-cell protein
      tyrosine phosphatase, TCPTP; megakaryocyte protein-tyrosine phosphatase, PTP
      MEG2; Src homology phosphatase 1, SHP-1 and Src homology phosphatase 2, SHP-2)
      was investigated. The oxovanadium(IV) complexes were potent inhibitors of PTP1B,
      TCPTP, PTP-MEG2, SHP-1 and SHP-2, but exhibited different inhibitory abilities
      over different PTPs. Complexes 2 and 4 displayed better selectivity to PTP1B over
      the other four PTPs. Kinetic data showed that complex 2 inhibited PTP1B, TCPTP
      and SHP-1 with a noncompetitive inhibition mode, but a classical competitive
      inhibition mode for PTP-MEG2 and SHP-2. The results demonstrated that both the
      structures of vanadium complexes and the conformations of PTPs influenced PTP
      inhibition activity. The proper modification of the organic ligand moieties may
      result in screening potent and selective vanadium-based PTP1B inhibitors.

PMID- 22864522
TI  - Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with
      advanced melanoma.
AB  - Background Arginine deiminase (ADI) is an enzyme that degrades arginine, an amino
      acid that is important for growth and development of normal and neoplastic cells.
      Melanoma cells are auxotrophic for arginine, because they lack
      argininosuccinatesynthetase (ASS), a key enzyme required for the synthesis of
      arginine. Patients and methods Patients with advanced melanoma were treated with
      40, 80 or 160 IU/m(2) ADI-PEG 20 i.m. weekly. Primary endpoints were toxicity and
      tumor response, secondary endpoints included metabolic response by (18)FDG-PET,
      pharmacodynamic (PD) effects upon circulating arginine levels, and
      argininosuccinate synthetase tumor expression by immunohistochemistry. Results 31
      previously treated patients were enrolled. The main toxicities were grade 1 and 2
      adverse events including injection site pain, rash, and fatigue. No objective
      responses were seen. Nine patients achieved stable disease (SD), with 2 of these
      durable for >6 months. Four of the 9 patients with SD had uveal melanoma. PD
      analysis showed complete plasma arginine depletion in 30/31 patients by day 8.
      Mean plasma levels of ADI-PEG 20 correlated inversely with ADI-PEG 20 antibody
      levels. Immunohistochemical ASS expression analysis in tumor tissue was negative
      in 24 patients, whereas 5 patients had <5 % cells positive. Conclusions ADI-PEG
      20 is well tolerated in advanced melanoma patients and leads to consistent, but
      transient, arginine depletion. Although no RECIST responses were observed, the
      encouraging rate of SD in uveal melanoma patients indicates that it may be
      worthwhile to evaluate ADI-PEG 20 in this melanoma subgroup.

PMID- 22864524
TI  - In people aged over 45, increased time spent sitting daily is associated with
      increased risk of all-cause mortality independent of physical activity level.

PMID- 22864523
TI  - Influence of WNK3 on intracellular chloride concentration and volume regulation
      in HEK293 cells.
AB  - The involvement of WNK3 (with no lysine [K] kinase) in cell volume regulation
      evoked by anisotonic conditions was investigated in two modified stable lines of
      HEK293 cells: WNK3+, overexpressing WNK3 and WNK3-KD expressing a kinase inactive
      by a punctual mutation (D294A) at the catalytic site. This different WNK3
      functional expression modified intracellular Cl(-) concentration with the
      following profile: WNK3+ > control > WNK3-KD cells. Stimulated with 15% hypotonic
      solutions, WNK3+ cells showed less efficient RVD (13.1%), lower Cl(-) efflux and
      decreased (94.5%) KCC activity. WNK3-KD cells showed 30.1% more efficient RVD,
      larger Cl(-) efflux and 5-fold higher KCC activity, increased since the isotonic
      condition. Volume-sensitive Cl(-) currents were similar in controls, WNK3+ cells,
      and WNK3-KD cells. Taurine efflux was not evoked at H15%. These results show a
      WNK3 influence on RVD in HEK293 cells via increasing KCC activity. Hypertonic
      medium induced cell shrinkage and RVI. In both WNK3+ and WNK3-KD cells, RVI and
      NKCC activity were increased, in WNK3+ cells presumably by enhanced NKCC
      phosphorylation, and in WNK3-KD cells via the [Cl(-)](i) reduction induced by the
      higher KCC activity in characteristic of these cells. These results support the
      role of WNK3 in modulation of intracellular Cl(-) concentration, in RVD, and
      indirectly on RVI, via its effects on KCC and NKCC activity. WNK3 in HEK293 cells
      is expressed as puncta at the intercellular junctions and diffusely at the
      cytosol, while the inactive kinase was found concentrated at the Golgi area.
      Cells with inactive WNK3 exhibited a marked change of cell phenotype.

PMID- 22864525
TI  - Gadolinium distribution in cochlear perilymph: differences between intratympanic
      and intravenous gadolinium injection.
AB  - INTRODUCTION: Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR)
      imaging 24 h after intratympanic gadolinium injection (IT method) or 4 h after
      intravenous injection (IV method) has been used to visualize endolymphatic
      hydrops in Meniere's disease. The aims of this study were to evaluate the
      difference in gadolinium distribution in cochlear perilymph between the two
      methods by comparing the enhancement of the basal and apical turns and clarify
      the pharmacokinetics in cochlear perilymph. METHODS: A total of 24 ears of 22
      patients who underwent the IT method (gadolinium-diethylene-triamine pentaacetic
      acid was diluted eightfold with saline) and 28 ears of 17 patients who underwent
      the IV method (double dose of gadoteridol (0.5 mmol/ml); 0.2 mmol/kg body weight
      in total amount) at 3 T was analyzed retrospectively. Regions of interest of the
      perilymph of the cochlear basal turn (B), of the apical turn (A), and the medulla
      oblongata (M) were determined on each patient. The signal intensity ratios
      between B and M (BMR), A and M (AMR), and A and B (ABR) were subsequently
      evaluated. RESULTS: The IT-BMR (2.63 +/- 1.22) was higher than the IV-BMR (1.46
      +/- 0.45) (p < 0.001). There was no significant difference between the IT- (1.46
      +/- 0.76) and IV-AMRs (1.21 +/- 0.48) (p = 0.15). The IT-ABR (0.58 +/- 0.17) was
      lower than the IV-ABR (0.84 +/- 0.22) (p < 0.001). CONCLUSION: Gadolinium was
      predominantly distributed in the basal turn compared with the apical turn in the
      IT method, whereas it was more uniformly distributed in the IV method. These
      characteristics might reflect the distribution of therapeutic medications
      administered either intratympanically or systemically.

PMID- 22864526
TI  - Strictly diastereocontrolled photocyclodimerization of 2-anthracenecarboxylates
      tethered to cyclic tetrasaccharides.
AB  - Photocyclodimerization of 2-anthracenecarboxylate tethered to a cyclic
      nigerosylnigerose scaffold gave a single chiral cyclodimer (out of two achiral
      and two chiral stereoisomers) in 99% optical and 96% chemical yields, achieving
      the ultimate stereocontrol of the supramolecular photochirogenesis in aqueous
      solution at 25  degrees C.

PMID- 22864527
TI  - Oral mucosa produces cytokines and factors influencing osteoclast activity and
      endothelial cell proliferation, in patients with osteonecrosis of jaw after
      treatment with zoledronic acid.
AB  - OBJECTIVES: The intravenous injection of bisphosphonates, currently used as
      treatment for osteoporosis, bone Paget's disease, multiple myeloma, or bone
      metastases, can cause jaw bone necrosis especially in consequence of trauma. The
      present research aimed to clarify the mechanisms underlying bone necrosis,
      exploring involvement of the oral mucosa "in vivo." PATIENTS AND METHODS:
      Specimens of oral mucosa were removed from bisphosphonate-treated patients with
      or without jaw bone necrosis. In mucosa specimens, expression was evaluated of:
      cytokines involved in the inflammatory process, factors involved in osteoclast
      activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and
      osteoprotegerin, a factor involved in cell proliferation, namely
      hydroxymethylglutaryl coenzyme A reductase, and a factor involved in
      angiogenesis, namely vascular endothelial growth factor (VEGF). RESULTS:
      Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated
      in mucosa from patients with versus without jaw necrosis, whereas
      hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.
      CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate
      released from the bone, can contribute to the development of jaw necrosis,
      reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl
      coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as
      shown by the increased RANKL/osteoprotegerin ratio. CLINICAL RELEVANCE: The
      results of this study suggest the importance of evaluating during bisphosphonate
      treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to
      monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the
      determination of these factors could be carried out in crevicular fluid.

PMID- 22864528
TI  - Impact of depressive symptoms on prosthetic status--results of the study of
      health in Pomerania (SHIP).
AB  - OBJECTIVES: Previous investigations have confirmed that every fifth dental
      patient suffers from clinically significant depressive symptoms. However, the
      putative impact of depressive symptoms on the prosthetic status has not been
      addressed in these studies. The objective of this study was to investigate the
      association between depressive symptoms and prosthetic status based on data from
      the Study of Health in Pomerania (SHIP-0). METHODS: Data from 2,135 participants
      aged 30 to 59 years were analyzed. A classification (six classes regarding the
      number and position of missing teeth per jaw) was used to identify the degree of
      prosthetic status (no/suboptimal/optimal tooth replacement). The presence of
      depressive symptoms was assessed with a modified version of von Zerssen's
      complaints scale. Screening for lifetime diagnoses of mental disorders was
      performed with the Composite International Diagnostic-Screener (CID-S).
      Multivariable logistic regressions including several confounders were calculated.
      RESULTS: A significant protective dose-response effect of depressive symptoms on
      prosthetic status was found only in men for the lower jaw [0-1 depressive
      symptoms: odds ratio (OR) = 3.84, 95 % confidence interval (CI, 1.65-8.92), p <
      0.01; 2-3: OR = 2.87 (CI, 1.22-6.74), p < 0.05; reference, >=8; adjusted for age,
      school education, smoking status, household income, marital status, living
      without a partner, risky alcohol consumption, obesity, diabetes, and physical
      activity]. There was no such association in women or for the upper jaw. The
      analyses using the CID-S confirmed these results. CONCLUSIONS: In the lower jaw,
      men with depressive symptoms had a better prosthetic status than men without
      depressive symptoms suggesting a higher level of concern regarding their personal
      health. CLINICAL RELEVANCE: If dentists might have an opportunity to identify men
      with depressive symptoms they can provide a wide range of treatment options that
      may enhance patients' self-esteem and contribute to the patient' well-being.
      Furthermore, depressive symptoms could indicate a discrepancy between self
      perception of the dental health and the actual status which influence the
      dentists' treatment decision making.

PMID- 22864529
TI  - Effects of open mouth and rubber dam on upper airway patency and breathing.
AB  - OBJECTIVES: Rubber dams increase the quality and safety of dental treatment.
      However, the condition of a rubber dam over an open mouth may also obstruct the
      route for respiration. We tested whether an open mouth with or without a rubber
      dam would affect upper airway patency and breathing pattern. MATERIALS AND
      METHODS: Twenty young healthy volunteers were imaged with a magnetic resonance
      (MR) system under three conditions: mouth closed, mouth open, and rubber dam with
      mouth open. Respiration was concurrently monitored with plethysmography. MRI
      slices of the upper airway were obtained at 5-mm thicknesses, and the size of the
      cross-sectional area of the upper airway was measured by image analysis software.
      Respiratory cycle duration and tidal volume were also measured with digital
      signal analysis software. RESULTS: The volume of the upper airway became
      significantly decreased with the mouth open. Analysis of each cross-sectional
      area of the upper airway revealed that while the oropharyngeal area was
      significantly narrower with an open mouth, the retropalatal and hypopharyngeal
      areas were not affected. Placing a rubber dam had no additional influence on
      upper airway patency but was seen to significantly shorten mean respiratory
      duration and decrease tidal volume. CONCLUSIONS: Open mouth position plays the
      largest role in decreased upper airway patency, and open mouth position with a
      rubber dam may further disrupt breathing pattern. CLINICAL RELEVANCE: Breathing
      pattern may become deteriorated by airway obstruction during dental treatments
      requiring a rubber dam.

PMID- 22864530
TI  - ART--a method on its way into dentistry.

PMID- 22864531
TI  - Response of VEGF to activation of viral receptors and TNFalpha in human mesangial
      cells.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in glomerular
      homeostasis as well as in the pathogenesis of kidney diseases as
      glomerulonephritis (GN) and diabetic nephropathy. Mesangial cells (MC), which are
      an integral part of the functional glomerular filtration barrier in that
      providing structural support, can behave like inflammatory cells and produce
      mediators as chemokines and growth factors; they are known to express viral
      receptors, with TLR3 having been attributed relevance in viral disease-associated
      GN. Experiments were performed on human MC in cell culture. Stimulation
      experiments were performed with poly (I:C) and hepatitis C RNA from patients with
      hepatitis C infection. We hereby show a TLR3-mediated upregulation of VEGF and
      its receptor subtype 2 (VEGF-R2) in human MC upon activation of viral receptors
      by poly (I:C) and hepatitis C virus. The increase in VEGF expression levels is
      further enhanced by tumor necrosis factor alpha (TNFalpha) which also induces the
      cytokines IL-6 and IL-8 as well as the chemokines MCP-1 and RANTES. These effects
      are potentiated by preincubation of MC with poly (I:C), just as the induction of
      the viral receptors TLR3, RIG-1, and MDA5 themselves. Moreover, MCP-1 itself is
      able to significantly increase mesangial VEGF expression. Therefore, with VEGF
      and VEGF-R2 being induced upon viral receptor activation in human MC, a novel
      role of TLR3 in mediating glomerular damage in virally induced or aggravated GN
      is inferred. TNFalpha and MCP-1 are seemingly important in amplifying VEGF
      effects in the setting of virally induced inflammation, with TNFalpha being also
      able to induce other mediators of glomerular pathology in GN.

PMID- 22864533
TI  - Response to: "Response to Different measures of 'genome-wide' DNA methylation
      exhibit unique properties in placental and somatic tissues.

PMID- 22864532
TI  - Thioredoxin reductase is inhibited by the carbamoylating activity of the
      anticancer sulfonylhydrazine drug laromustine.
AB  - The thioredoxin system facilitates proliferative processes in cells and is
      upregulated in many cancers. The activities of both thioredoxin (Trx) and its
      reductase (TrxR) are mediated by oxidation/reduction reactions among cysteine
      residues. A common target in preclinical anticancer research, TrxR is reported
      here to be significantly inhibited by the anticancer agent laromustine. This
      agent, which has been in clinical trials for acute myelogenous leukemia and
      glioblastoma multiforme, is understood to be cytotoxic principally via
      interstrand DNA crosslinking that originates from a 2-chloroethylating species
      generated upon activation in situ. The spontaneous decomposition of laromustine
      also yields methyl isocyanate, which readily carbamoylates thiols and primary
      amines. Purified rat liver TrxR was inhibited by laromustine with a clinically
      relevant IC(50) value of 4.65 MUM. A derivative of laromustine that lacks
      carbamoylating activity did not appreciably inhibit TrxR while another
      derivative, lacking only the 2-chloroethylating activity, retained its inhibitory
      potency. Furthermore, in assays measuring TrxR activity in murine cell lysates, a
      similar pattern of inhibition among these compounds was observed. These data
      contrast with previous studies demonstrating that glutathione reductase, another
      enzyme that relies on cysteine-mediated redox chemistry, was not inhibited by
      methylcarbamoylating agents when measured in cell lysates. Mass spectrometry of
      laromustine-treated enzyme revealed significant carbamoylation of TrxR, albeit
      not on known catalytically active residues. However, there was no evidence of 2
      chloroethylation anywhere on the protein. The inhibition of TrxR is likely to
      contribute to the cytotoxic, anticancer mechanism of action for laromustine.

PMID- 22864534
TI  - On-chip anticancer drug test of regular tumor spheroids formed in microwells by a
      distributive microchannel network.
AB  - This paper proposes a new cytotoxicity assay in a microfluidic device with
      microwells and a distributive microfluidic channel network for the formation of
      cancer cell spheroids. The assay can generate rapid and uniform cell clusters in
      microwells and test in situ cytotoxicity of anticancer drugs including sequential
      drug treatments, long term culture of spheroids and cell viability assays. Inlet
      ports are connected to the microwells by a hydraulic resistance network. This
      uniform distribution of cell suspensions results in regular spheroid dimensions.
      Injected cancer cells were trapped in microwells, and aggregated into tumor
      spheroids within 3 days. A cytotoxicity test of the spheroids in microwells was
      subsequently processed in the same device without the extraction of cells. The in
      situ cytotoxicity assay of tumor spheroids in microwells was comparable with the
      MTT assay on hanging drop spheroids using a conventional 96-well plate. It was
      observed that the inhibition rate of the spheroids was less than that in the 2D
      culture dish and the effect on tumor spheroids was different depending on the
      anticancer drug. This device could provide a convenient in situ assay tool to
      assess the cytotoxicity of anticancer drugs on tumor spheroids, offering more
      information than the conventional 2D culture plate.

PMID- 22864535
TI  - Parental sleep experiences on the pediatric oncology ward.
AB  - PURPOSE: Parents of pediatric oncology patients are encouraged to sleep on the
      ward with their child to provide additional care throughout the night. The
      purpose of this study was to provide the first prevalence estimates of self
      reported sleep quantity and quality among parents accommodated on the pediatric
      oncology ward, compared to parents of age-matched controls. METHODS: Parents of
      children receiving in-patient cancer treatment and parents of healthy, age
      matched children completed a self-report questionnaire, including validated
      measures of parental sleep and psychological distress, demographic, and clinical
      characteristics. RESULTS: In total, 114 parents participated (52 parents of
      children with cancer; 62 control parents; over all response rate 70 %). Parents
      on the pediatric oncology ward reported sleeping 5.7 h (SD = 1.8) on average, in
      comparison to control parents who reported sleeping 7.0 h at home (SD = 1.4; t =
      4.3, p < 0.001). Parents reported waking an average of 4.6 times (SD = 0.3) per
      night on the ward, compared to control parents who reported 2.0 (SD = 0.2)
      nighttime awakenings (t = 7.69, p < 0.001). Parents of children with cancer were
      significantly more likely to report that they had slept "badly" (67.3 versus 21.0
      %; chi(2) = 21.9, p < 0.001). Significant predictors of sleep duration included
      anxiety (p = 0.013) and caffeine consumption (p = 0.017). Parents who slept on
      the ward attributed poor sleep to feelings of anxiety, environmental noise, and
      child-related factors. CONCLUSIONS: Parents who sleep on the pediatric oncology
      ward experience poor sleep outcomes, including inadequate duration and frequent
      interruptions. The detrimental effects of sleep deprivation on parents' ability
      to cope during this challenging time require further investigation and
      intervention.

PMID- 22864538
TI  - Ecological study of revegetated coal mine spoil of an Indian dry tropical
      ecosystem along an age gradient.
AB  - Mineral nitrogen (MN), belowground (root) biomass (BGB), soil nitrogen (N)
      mineralization (NM), microbial biomass N (MBN) and mine dump stability of a
      revegetated mine spoil were studied after 2, 6, 10 and 12 years of re-vegetation
      on coal mine spoil site. MN in revegetated mine spoil ranged from 7.4 to 11.6 kg
      ha(-1), NM from 38.4 to 252 kg ha(-1) year(-1), MBN from 86 to 426 kg ha(-1), and
      BGB from 380 to 3,750 kg ha(-1). Mining caused decline of physico-chemical
      characteristics of soil like MN by 46 %, N-mineralization by 92 %, MBN values by
      91 %, respectively compared to forest ecosystems and reduction of total plant
      biomass (above ground and below ground). Revegetation of mine spoil caused
      increase in MN values by 12, 36 and 76 %, BGB values by 380, 1770 and 3750 times,
      NM values by 0.6, 3.58 and 9.5 times and MBN values by 0.43, 2.77, and 6.07 times
      in 2, 6 and 12 years, respectively. BGB was highly correlated with MN and MBN.
      Clay content was positively correlated to MN, NM, and the age of revegetation (P
      < 0.01). Numerical modelling indicated that revegetation increased the dump slope
      stability with a factor of safety from 1.2 to 1.4, 1.7, 1.9 and 2.1 after 2, 6,
      10 and 12 years, respectively. Thus, long-term revegetation was found to enhance
      the dump stability and the soil fertility status in mine spoil, where plant
      biomass and microbial biomass provide major contributions in ecological
      redevelopment of the mine spoil.

PMID- 22864536
TI  - Taste alteration in breast cancer patients treated with taxane chemotherapy:
      experience, effect, and coping strategies.
AB  - PURPOSE: This study examined the experience and coping strategies for taste
      alteration in female breast cancer patients treated with docetaxel or paclitaxel.
      METHODS: A purposive sample of 25 patients currently receiving docetaxel or
      paclitaxel or within 6 months of having completed treatment was recruited. Semi
      structured interviews and patient-level data were utilized for this exploratory
      descriptive study. Interview data were analyzed with the constant comparative
      method; patient-level data were abstracted from the electronic medical record.
      RESULTS: Of all side effects reported from taxanes, the most common was taste
      alteration (8 of 10 docetaxel patients, 3 of 15 paclitaxel patients). Women that
      experience taste alteration chose not to eat as much, ate on an irregular
      schedule, and/or lost interest in preparing meals for themselves and/or their
      family. Women adopted a variety of new behaviors to deal with the taste
      alteration and its effects, including trying new recipes, eating strongly
      flavored foods, honoring specific food cravings, eating candy before meals,
      cutting food with lemon, drinking sweetened drinks, using plastic eating
      utensils, drinking from a straw, brushing their teeth and tongue before meals,
      and using baking soda and salt wash or antibacterial mouthwash. CONCLUSIONS:
      Taste alteration affects breast cancer patients' lives, and they develop
      management strategies to deal with the effect. While some self-management
      strategies can be seen as positively adaptive, the potential for increased
      caloric consumption and poor eating behaviors associated with some coping
      strategies may be a cause for concern given the observation of weight gain during
      breast cancer treatment and association of obesity with poor treatment outcomes
      in breast cancer patients. Further studies are warranted to determine the overall
      burden of this symptom and measurement of cancer and non-cancer-related
      consequences of these behavioral adaptations.

PMID- 22864540
TI  - Random motion with interfacial contact: driven diffusion vis-a-vis mechanical
      activation.
AB  - Rolling of a small sphere on a patterned support of an elastomer is governed by a
      non-linear friction. No motion occurs when the external field is weaker than the
      frictional resistance. However, with the intervention of an external noise, a
      viscous friction like behavior emerges; thus the sphere rolls with a uniform
      drift velocity that is proportional to the applied field. At a very low noise
      strength, the sphere exhibits a stick-slip behavior with motion occurring always
      along the bias. With the increase in the noise strength, the sphere exhibits a
      diffusive drift accompanied with forward and backward displacements. During this
      stage of driven diffusive motion, the ratio of the integrated probabilities of
      the negative-to-positive work fluctuations decreases monotonically with the time
      of observation, from which a temperature like intensive parameter can be
      estimated. This parameter conforms to Einstein's ratio of diffusivity and
      mobility that increases almost linearly, even though the diffusivity increases
      super-linearly, with the strength of the noise. A new barrier crossing experiment
      is introduced that can be performed either with a hard (e.g. a steel ball) or
      with a soft (e.g. a water drop) sphere in contact with a periodically undulated
      substrate. The frequency of barrier crossing follows a transition state equation
      allowing a direct estimation of the effective temperature. These experiments as
      well as certain numerical simulations suggest that the effective temperature of a
      system controlled by a non-linear friction may not have a unique value.

PMID- 22864539
TI  - Administration of a murine diet supplemented with conjugated linoleic acid
      increases the expression and activity of hepatic uncoupling proteins.
AB  - Daily intake of conjugated linoleic acid (CLA) has been shown to reduce body fat
      accumulation and to increase body metabolism; this latter effect has been often
      associated with the up-regulation of uncoupling proteins (UCPs). Here we
      addressed the effects of a CLA-supplemented murine diet (~2 % CLA mixture, cis-9,
      trans-10 and trans-10, cis-12 isomers; 45 % of each isomer on alternating days)
      on mitochondrial energetics, UCP2 expression/activity in the liver and other
      associated morphological and functional parameters, in C57BL/6 mice. Diet
      supplementation with CLA reduced both lipid accumulation in adipose tissues and
      triacylglycerol plasma levels, but did not augment hepatic lipid storage. Livers
      of mice fed a diet supplemented with CLA showed high UCP2 mRNA levels and the
      isolated hepatic mitochondria showed indications of UCP activity: in the presence
      of guanosine diphosphate, the higher stimulation of respiration promoted by
      linoleic acid in mitochondria from the CLA mice was almost completely reduced to
      the level of the stimulation from the control mice. Despite the increased
      generation of reactive oxygen species through oxi-reduction reactions involving
      NAD(+)/NADH in the Krebs cycle, no oxidative stress was observed in the liver. In
      addition, in the absence of free fatty acids, basal respiration rates and the
      phosphorylating efficiency of mitochondria were preserved. These results indicate
      a beneficial and secure dose of CLA for diet supplementation in mice, which
      induces UCP2 overexpression and UCP activity in mitochondria while preserving the
      lipid composition and redox state of the liver.

PMID- 22864541
TI  - Brownian dynamics simulation of monolayer formation by deposition of colloidal
      particles: a kinetic study at high bulk particle concentration.
AB  - Brownian dynamics simulations (BDS) of sedimentation and irreversible adsorption
      of colloidal particles on a planar surface were carried out at bulk particle
      volume fractions (phi) in the range 0.05 to 0.25. The sedimentation and
      adsorption of colloidal particles were simulated as a non-sequential process that
      allows simultaneous settling and adsorption of particles. A kinetic model for the
      formation of particle monolayers based on the available surface fraction
      (theta(A)) is proposed to predict simulation results. The simulations show a
      value of 0.625 for the maximum fractional surface coverage (theta(infinity)) and
      a monolayer structure insensitive to phi. However, the kinetic order of the
      monolayer formation process has a strong dependence with phi, changing from a
      value close to a unit, at low phi, to a value around two at high phi. This change
      in the kinetic reaction order is associated to differences of particle adsorption
      mechanism on the surface. At low phi values, the monolayer formation is achieved
      by independent adsorption of single particles and the reaction order is close to
      1. At high phi values, the simultaneous adsorption of two particles on the
      surface leads to an increase of the reaction order to values close to 2.

PMID- 22864542
TI  - A circle swimmer at low Reynolds number.
AB  - Swimming in circles occurs in a variety of situations at low Reynolds number.
      Here we propose a simple model for a swimmer that undergoes circular motion,
      generalising the model of a linear swimmer proposed by Najafi and Golestanian
      (Phys. Rev. E 69, 062901 (2004)). Our model consists of three solid spheres
      arranged in a triangular configuration, joined by two links of time-dependent
      length. For small strokes, we discuss the motion of the swimmer as a function of
      the separation angle between its links. We find that swimmers describe either
      clockwise or anticlockwise circular motion depending on the tilting angle in a
      non-trivial manner. The symmetry of the swimmer leads to a quadrupolar decay of
      the far flow field. We discuss the potential extensions and experimental
      realisation of our model.

PMID- 22864543
TI  - Active and driven hydrodynamic crystals.
AB  - Motivated by the experimental ability to produce monodisperse particles in
      microfluidic devices, we study theoretically the hydrodynamic stability of driven
      and active crystals. We first recall the theoretical tools allowing to quantify
      the dynamics of elongated particles in a confined fluid. In this regime
      hydrodynamic interactions between particles arise from a superposition of
      potential dipolar singularities. We exploit this feature to derive the equations
      of motion for the particle positions and orientations. After showing that all
      five planar Bravais lattices are stationary solutions of the equations of motion,
      we consider separately the case where the particles are passively driven by an
      external force, and the situation where they are self-propelling. We first
      demonstrate that phonon modes propagate in driven crystals, which are always
      marginally stable. The spatial structures of the eigenmodes depend solely on the
      symmetries of the lattices, and on the orientation of the driving force. For
      active crystals, the stability of the particle positions and orientations depends
      not only on the symmetry of the crystals but also on the perturbation wavelengths
      and on the crystal density. Unlike unconfined fluids, the stability of active
      crystals is independent of the nature of the propulsion mechanism at the single
      particle level. The square and rectangular lattices are found to be linearly
      unstable at short wavelengths provided the volume fraction of the crystals is
      high enough. Differently, hexagonal, oblique, and face-centered crystals are
      always unstable. Our work provides a theoretical basis for future experimental
      work on flowing microfluidic crystals.

PMID- 22864544
TI  - Expanding the genetic code of Drosophila melanogaster.
AB  - Genetic code expansion for unnatural amino acid mutagenesis has, until recently,
      been limited to cell culture. We demonstrate the site-specific incorporation of
      unnatural amino acids into proteins in Drosophila melanogaster at different
      developmental stages, in specific tissues and in a subset of cells within a
      tissue. This approach provides a foundation for probing and controlling processes
      in this established metazoan model organism with a new level of molecular
      precision.

PMID- 22864545
TI  - Infantile juvenile xanthogranuloma of the chest wall mimicking mesenchymal
      hamartoma: report of a case.
AB  - Juvenile xanthogranuloma (JXG) is essentially a benign neoplasm arising from any
      site on the body; however, there has so far been only one report of JXG located
      on the chest wall involving a rib. This report presents a rare case finally
      diagnosed as JXG based on histopathological and immunohistochemical examinations.

PMID- 22864546
TI  - Stapled intestinal anastomosis is a simple and reliable method for management of
      intestinal caliber discrepancy in children.
AB  - PURPOSE: Popularity of minimally invasive surgeries has led to the development of
      stapled intestinal anastomosis for adults. The advanced instruments used in this
      technique are getting suitable with the small intestinal lumens of neonates and
      infants. We reviewed and compared the intraoperative and postoperative results of
      stapled and hand-sewn anastomoses in children. METHODS: The operative data of
      children who underwent stapled and hand-sewn anastomoses between March 2005 and
      December 2011 were collected and analyzed retrospectively. Furthermore, we
      compared patients who underwent anastomoses for colostomy closure of anorectal
      malformation (4 stapled, 9 hand-sewn) and those who underwent anastomoses for
      treatment of ileal atresia (3 stapled, 11 hand-sewn). RESULTS: In the 47 patients
      who underwent stapled anastomosis, no intraoperative complications were observed
      and postoperative complications included wound infection (n = 3), delayed gastric
      emptying (n = 1), and ileus (n = 1). No complications suggesting anastomotic
      dilatation were identified. It was observed that patients who underwent stapled
      anastomosis for colostomy takedown with caliber discrepancy had significantly
      shorter surgery time than those who underwent hand-sewn anastomosis. CONCLUSION:
      Our results suggest that stapled anastomosis is safe and effective for various
      surgical diseases in neonates, infants, and children.

PMID- 22864547
TI  - Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in
      transformation.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a transmissible lung
      cancer in sheep. A unique feature is that JSRV envelope protein is also the
      oncogene for this virus. Previous studies have identified the cytoplasmic tail
      (CT) of the envelope transmembrane (TM) protein as critical for transformation
      although other regions of Env have also been implicated. In this study, the roles
      of other Env regions in transformation were investigated. Chimeras between JSRV
      Env and the Env of a related non-oncogenic endogenous retrovirus (enJSRV, 5F16)
      were used. A chimera containing the membrane-spanning region (MSR) of enJSRV
      inserted into JSRV Env showed substantially reduced transformation, indicating
      that the MSR plays a role in transformation. Transformation by this chimera was
      highly dependent on both Ras/Raf/MEK/MAPK and PI3K/Akt/mTOR signaling. A chimera
      containing the two amino acids in the TM ectodomain that distinguish JSRV and
      enJSRV showed modestly reduced transformation. Chimeras in the SU protein
      indicated that the amino terminal region of SU contributes to transformation,
      while the C-terminal part is not important. To test if Env trimerization is
      important for transformation, we mutated a leucine-rich sequence in the putative
      trimerization domain in the ectodomain of TM (Tri-M). This mutant could not
      transform cells and it did not oligomerize. However, Tri-M could complement a non
      transforming mutant CT mutant (Y590F) so oligomerization is not necessary for at
      least some aspects of transformation. These experiments provide new insight into
      the regions and residues of JSRV Env protein necessary for oncogenic
      transformation.

PMID- 22864548
TI  - Genetic characterization of Erve virus, a European Nairovirus distantly related
      to Crimean-Congo hemorrhagic fever virus.
AB  - Erve virus (ERVEV) is a European Nairovirus that is suspected to cause severe
      headache (thunderclap headache) and intracerebral hemorrhage. The mode of
      transmission to humans (ticks or mosquitoes) is still unknown. Currently, no
      standardized testing method for ERVEV exists and only a small partial sequence of
      the polymerase gene is available. Here, we present the first complete genome
      sequence of ERVEV S, M, and L segments. Phylogenetic comparison of the amino acid
      sequence of the L-protein (RNA-dependent RNA polymerase) revealed only 48 %
      homology to available L-protein sequences of other Nairoviruses like Crimean
      Congo hemorrhagic fever virus, Nairobi sheep disease virus, Hazara virus, Kupe
      virus, and Dugbe virus. Among themselves, these Nairoviruses show 62-89 %
      homology in the L-protein sequences. Therefore, ERVEV seems to be only distantly
      related to other Nairoviruses. The new sequence data can be used for the
      development of diagnostic methods and the identification of the natural vector.

PMID- 22864549
TI  - Complete sequence of an Apple stem grooving virus (ASGV) isolate from China.
AB  - The complete genome sequence of a Chinese isolate of Apple stem grooving virus
      (ASGV) was determined to be 6,495 nucleotides long, single-stranded, plus-sense
      RNA. The viral RNA has two overlapping open reading frames (ORFs): ORF1 and ORF2.
      Compared with the genome sequences of ASGV isolates available in GenBank, the
      nucleotide identities ranged from 80.1 to 86.3 %. The amino acid identities of
      proteins encoded by ORF1 and ORF2 ranged from 79.5 to 86.1 % and 82.0 to 85.9 %,
      respectively.

PMID- 22864550
TI  - The environmental pollution perception of residents in coal mining areas: a case
      study in the Hancheng mine area, Shaanxi Province, China.
AB  - The environmental behavior of the residents depends on their perception of
      environmental pollution. Hence, it is important for scientific and policy experts
      to research on the impact of the environmental pollution perception of local
      residents. Owing to the richness of natural resources, Hancheng coal mine areas
      are abound in heavy industries, and environmental pollution is serious and
      typical in this area, thus, the residents are anxious about their health. Using
      questionnaires, this paper surveys the perception of residents living in the coal
      mine area. The influential factors of environmental perception were analyzed by
      the Rank Sum Test. The results were: (1) the majority of the residents in the
      coal mine area are not satisfied with their living environment. The perception
      order of pollution severity is: air pollution > noise pollution > sanitation >
      water pollution. The residents think that pollution is mainly caused by coal
      processing. Hence, coal mining is not the main reason of the pollution in the
      coal mine area. (2) Age and length of residence have significant positive effects
      on perceptions of air, water, and noise pollutions; whereas education has a
      significant negative effect on perceptions of water and noise pollutions, as well
      as sanitation. This phenomenon can be explained by the various cultural groups
      having varied perceptions on the environmental pollution. In addition, proximity
      to mine has significant negative effect on perceptions of water and noise
      pollution. In conclusion, the paper discusses the effects of demographical and
      social factors on the perception of environmental pollution and gives suggestions
      on the planning and management of the environment.

PMID- 22864551
TI  - Landslide susceptibility assessment and validation in the framework of municipal
      planning in Portugal: the case of Loures Municipality.
AB  - The legislation that demands the evaluation of landslide susceptibility in
      Portugal at the municipal level is the National Ecological Reserve (NER). A
      methodology for the evaluation of landslide susceptibility to be used in
      municipal planning is applied in Loures Municipality (169.3 km2) located north of
      Lisbon (Portugal). A landslide inventory was made for the whole area interpreting
      orthophoto maps and aerial photographs and using standard geomorphologic
      techniques in field work. It consists of 686 polygons, each polygon representing
      a rotational, a deep translational or a shallow translational slide, and is
      integrated into a GIS database. Landslide susceptibility is evaluated using
      algorithms based on statistical/probabilistic analysis (Information Value Method)
      over unique-condition terrain units in a raster basis. Three susceptibility
      models are elaborated independently according to the type of slide (rotational,
      deep translational, shallow translational). The landslide susceptibility maps are
      prepared by sorting all pixels according to the pixel susceptibility value in
      descending order. The robustness and accuracy of the landslide susceptibility
      models are evaluated by prediction-rate curves, which are used for the
      quantitative interpretation of the landslide susceptibility maps. Unstable slopes
      that have to be included into the National Ecological Reserve are extracted from
      the three susceptibility maps following the general rules to draw the NER that
      state that the area to be included in the NER should guarantee the inclusion of
      at least 70 % of the landslides identified in the landslide inventory. The
      obtained results allow us to conclude that 70 % of the future landslides should
      occur in these areas, classified as most susceptible to landslides corresponding
      to 20.3 % of the total area of Municipality. Thus, the consideration of these
      20.3 % as regards prevention and protection of landslide risk could potentially
      reduce damage resulting from 70 % of future landslides in the Loures
      Municipality.

PMID- 22864552
TI  - Retrospective analysis of outcome data with regards to the use of Phisio(r)-,
      Bioline(r)- or Softline(r)-coated cardiopulmonary bypass circuits in cardiac
      surgery.
AB  - BACKGROUND: Numerous cardiopulmonary bypass circuits with various coatings
      designed to reduce the inflammatory response and to provide better
      hemocompatibility are available. The aim of this study was to compare the effect
      of phosphorylcholine-coated, albumin-heparin-coated and synthetic polymer-coated
      perfusion tubing systems on patient outcome. METHODS: We performed a
      retrospective database review of elective patients between January 1st 2010 and
      December 31st 2010. Demographics, preoperative, operative, postoperative data and
      follow-up were collected and statistically analysed. RESULTS: We identified 201
      patients and formed three groups: Group 1 with phosphorylcholine coating (n=133),
      Group 2 with albumin-heparin coating (n=32) and Group 3 synthetic polymer coating
      (n=36). Mean age was 68 +/- 11 years, additive Euroscore 5.8 +/- 2.7. In-hospital
      outcomes were comparable between the groups without statistically significant
      differences. The overall 30-day and 1-year late survival were 98.5% and 96.7 +/-
      1.9%, respectively. CONCLUSIONS: Our findings suggest that in-hospital and follow
      up outcomes are comparable in cardiac surgery patients after using either
      phosphorylcholine-coated, albumin-heparin-coated or synthetic polymer-coated
      circuits during cardiopulmonary bypass.

PMID- 22864554
TI  - Inorganic-organic hybrid compounds based on octamolybdates and multidentate N
      donor ligand: syntheses, structures, photoluminescence and photocatalysis.
AB  - Six inorganic-organic hybrid compounds, namely, [Cu(2)(2,4'-tmbpt)(2)(beta
      Mo(8)O(26))(H(2)O)(2)].7H(2)O (1), [Cu(2,4'-tmbpt)(gamma
      Mo(8)O(26))(0.5)(H(2)O)].H(2)O (2), [Co(2,4'-Htmbpt)(2)(gamma
      Mo(8)O(26))(H(2)O)(2)] (3), [Zn(2,4'-Htmbpt)(2)(gamma-Mo(8)O(26))(H(2)O)(2)] (4),
      [Ni(2,4'-tmbpt)(alpha-Mo(8)O(26))(0.5)(H(2)O)].2.5H(2)O (5) and [Ag(2,4'
      Htmbpt)(beta-Mo(8)O(26))(0.5)] (6), have been synthesized under hydrothermal
      conditions (2,4'-tmbpt = 1-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-pyridyl)-5-(4
      pyridyl)-1,2,4-triazole). The structures of compounds 1-6 have been determined by
      single-crystal X-ray diffraction analyses and characterized by infrared spectra
      (IR), elemental analyses, powder X-ray diffraction (PXRD) analyses and
      thermogravimetric analyses (TGA). Compound 1 shows a 3D (3,4)-connected framework
      constructed by the 2D Cu(II)-organic fragments and [beta-Mo(8)O(26)](4-) anions.
      Compound 2 exhibits a 2D layer structure based on Cu(II)-organic chains and
      [gamma-Mo(8)O(26)] chains. The layers are extended into a 3D supramolecular
      framework by hydrogen-bonding interactions. Compounds 3 and 4 are isostructural,
      and display 1D chain structures. The chains are further interlinked by hydrogen
      bonding interactions to form 3D supramolecular architectures. Compound 5 shows a
      3D framework based on the 2D Ni(II)-organic fragments and [alpha-Mo(8)O(26)](4-)
      anions. In compound 6, the 1D chains constructed by the Ag(I) ions, 2,4'-Htmbpt
      ligands and [beta-Mo(8)O(26)](4-) anions are extended by hydrogen-bonding
      interactions into a 2D supramolecular layer. Each layer threads into the adjacent
      layers, yielding a 2D -> 3D interdigitated structure. Moreover, the
      photoluminescent properties of 4 and 6, the optical band gaps of 1-6, and the
      photocatalytic properties of 1-6 have also been investigated.

PMID- 22864553
TI  - Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine
      protease cathepsin-S.
AB  - Proteolytic processing of the amiloride-sensitive epithelial sodium channel
      (ENaC) by serine proteases is known to be important for channel activation.
      Inappropriate ENaC activation by proteases may contribute to the pathophysiology
      of cystic fibrosis and could be involved in sodium retention and the pathogenesis
      of arterial hypertension in the context of renal disease. We hypothesized that in
      addition to serine proteases, cathepsin proteases may activate ENaC. Cathepsin
      proteases belong to the group of cysteine proteases and play a pathophysiological
      role in inflammatory diseases. Under pathophysiological conditions, cathepsin-S
      (Cat-S) may reach ENaC in the apical membrane of epithelial cells. The aim of
      this study was to investigate the effect of purified Cat-S on human ENaC
      heterologously expressed in Xenopus laevis oocytes and on ENaC-mediated sodium
      transport in cultured M-1 mouse renal collecting duct cells. We demonstrated that
      Cat-S activates amiloride-sensitive whole-cell currents in ENaC-expressing
      oocytes. The stimulatory effect of Cat-S was preserved at pH 5. ENaC stimulation
      by Cat-S was associated with the appearance of a gammaENaC cleavage fragment at
      the plasma membrane indicating proteolytic channel activation. Mutating two
      valine residues (V182 and V193) in the critical region of gammaENaC prevented
      proteolytic activation of ENaC by Cat-S. Pre-incubation of the oocytes with the
      Cat-S inhibitor morpholinurea-leucine-homophenylalanine-vinylsulfone-phenyl
      (LHVS) prevented the stimulatory effect of Cat-S on ENaC. In contrast, LHVS had
      no effect on ENaC activation by the prototypical serine proteases trypsin and
      chymotrypsin. Cat-S also stimulated ENaC in differentiated renal epithelial
      cells. These findings demonstrate that the cysteine protease Cat-S can activate
      ENaC which may be relevant under pathophysiological conditions.

PMID- 22864555
TI  - 7-Selenabicyclo[2.2.1]heptane.
AB  - Thermolysis of a benzene solution of N-[4-(p-(methoxybenzyl)seleno)cyclohexanoyl]
      N,S-dimethyldithiocarbonate affords the hitherto unknown 7
      selenabicyclo[2.2.1]heptane in 48% conversion and in 20% yield after
      chromatography. G3(MP2)-RAD calculations predict a rate constant of 5 * 10(4) s(
      1) at 80  degrees C (3.8 * 10(6) s(-1) at 200  degrees C) for the intramolecular
      homolytic substitution process involved in this cyclization.

PMID- 22864557
TI  - Au/SiO2 as a highly active catalyst for the selective oxidation of silanes to
      silanols.
AB  - Au/SiO(2), which was prepared properly to have a high dispersion of gold
      nanoparticles, acts as an extremely active catalyst for the selective oxidation
      of a variety of silanes. It outperforms other reducible oxide supported gold
      catalysts thanks to the affinity of the silica support to the silane substrate.

PMID- 22864556
TI  - Dose-response relationship of locally applied nimodipine in an ex vivo model of
      cerebral vasospasm.
AB  - INTRODUCTION: Cerebral vasospasm is a severe complication of subarachnoid
      hemorrhage (SAH). The calcium channel inhibitor nimodipine has been used for
      treatment of cerebral vasospasm. No evidence-based recommendations for local
      nimodipine administration at the site of vasospasm exist. The purpose of this
      study was to quantify nimodipine's local vasodilatory effect in an ex vivo model
      of SAH-induced vasospasm. METHODS: SAH-induced vasospasm was modeled by
      contracting isolated segments of rat superior cerebellar arteries with a
      combination of serotonin and a synthetic analog of prostaglandin A(2). A pressure
      myograph system was used to determine vessel reactivity of spastic as well as non
      spastic arteries. RESULTS: Compared to the initial vessel diameter, a combination
      of serotonin and prostaglandin induced considerable vasospasm (55 +/- 2.5 %
      contraction; n = 12; p < 0.001). Locally applied nimodipine dilated the arteries
      in a concentration-dependent manner starting at concentrations as low as 1 nM (n
      = 12; p < 0.05). Concentrations higher than 100 nM did not relevantly increase
      the vasodilatory effect. Nimodipine's vasodilatory effect was smaller in spastic
      than in non-spastic vessels (n = 12; p < 0.05), which we assume to be due to
      structural changes in the vessel wall. CONCLUSION: The described ex vivo model
      allows to investigate the dose-dependent efficacy of spasmolytic drugs prior to
      in vivo experiments. Low concentrations of locally applied nimodipine have a
      strong vasodilatory effect, which is of relevance when considering the local
      application of nimodipine in cerebral vasospasm.

PMID- 22864558
TI  - Lack of anti-drug antibodies in patients with psoriasis well-controlled on long
      term treatment with tumour necrosis factor inhibitors.

PMID- 22864559
TI  - Spatial distribution of potentially bioavailable metals in surface soils of a
      contaminated sports ground in Galway, Ireland.
AB  - Assessing the environmental risk of metal contamination in soils requires the
      determination of both total (TCs) and bioavailable (BCs) element concentrations.
      A total of 200 surface (0-10 cm) soil samples were collected from an urban sports
      ground (South Park) in Galway, Ireland, a former landfill and dumping site, which
      is currently under remediation. The potential BCs of metals were measured using
      ethylene-diamine-tetra-acetic acid (EDTA) extraction followed by inductively
      coupled plasma-optical emission spectrometry analysis, while the TCs were
      determined using portable X-ray fluorescence spectrometry. It was found that Zn
      was primarily present in the insoluble residue (EDTA un-extractable) fraction in
      soils, with the median ratio of BCs/TCs 0.27. However, Pb and Cu had higher
      ratios of BCs/TCs (median values of 0.60 and 0.39, respectively) suggesting that
      they are potentially more bioavailable in the soils. The spatial distribution
      maps showed that both TCs and BCs for Cu, Pb and Zn in the study area were
      spatially heterogeneous. It was found that the BCs exhibited generally similar
      spatial patterns as their TCs of Cu, Pb and Zn: high values were mainly located
      in the west, north-east and south-east portions of the study area, where only a
      thin layer of topsoil existed. It was recommended that the current remediation
      action for this site needs to be carried out on an urgent basis.

PMID- 22864560
TI  - Assessing parent-child agreement in health-related quality of life among three
      health status groups.
AB  - PURPOSE: To examine parent-child agreement regarding a child's health-related
      quality of life (HRQOL) among three health status groups. METHODS: Parent-child
      agreement was evaluated for three health status groups of a population-based
      sample: (1) children with mental health problems (N = 461), (2) children with
      physical health problems (N = 281), and (3) healthy controls (N = 699). The
      KIDSCREEN-27 was used to assess HRQOL. The children were 9-14 years of age.
      RESULTS: Intraclass correlation coefficients were mostly good across all HRQOL
      scores and health status groups. This relatively high level of agreement was also
      reflected by the following findings: first, the AGREE group was the largest in
      three out of five HRQOL subscales in all health status groups; second, when
      disagreement occurred, it was often minor in magnitude. Despite this relatively
      high level of agreement, the means of self-ratings were significantly higher for
      all HRQOL scores and health status groups than the means of proxy ratings. These
      higher self-ratings were especially pronounced among children with mental health
      problems in certain HRQOL domains. CONCLUSIONS: Even though the level of parent
      child agreement regarding a child's HRQOL is relatively high, it should be
      considered that children (especially those with mental health problems) often
      report better HRQOL than their parents. It is, therefore, highly recommended that
      both proxy- and self-ratings are used to evaluate a child's HRQOL
      comprehensively.

PMID- 22864561
TI  - Adoptive immunotherapy of advanced melanoma.
AB  - Adoptive cell therapy (ACT) has emerged as an effective therapy for patients with
      metastatic melanoma. Since the first introduction of the protocol in 1988 [1],
      major improvements have been achieved with response rates of 40%-72% among
      patients who were resistant to previous treatment lines. Both cell product and
      conditioning regimen are major determinants of treatment efficacy; therefore,
      developing ACT protocols explore diverse ways to establish autologous intra
      tumoral lymphocyte cultures or peripheral effector cells as well as different
      lymphodepleting regimens. While a proof of feasibility and a proof of concept had
      been established with previous published results, ACT will need to move beyond
      single-center experiences, to confirmatory, multi-center studies. If ACT is to
      move into widespread practice, it will be necessary to develop reproducible high
      quality cell production methods and accepted lymphodepleting regimen. Two new
      drugs, ipilimumab (Yervoy, Bristol-Myers Squibb) and vemurafenib (Zelboraf,
      Roche), were approved in 2011 for the treatment of metastatic melanoma based on
      positive phase III trials. Both drugs show a clear overall survival benefit, so
      the timing of when to use ACT will need to be carefully thought out. In contrast
      to these 2 new, commercially available outpatient treatments, ACT is a personally
      specified product and labor-intensive therapy that demands both acquisition of
      high standard laboratory procedures and close clinical inpatient monitoring
      during treatment. It is unique among other anti-melanoma treatments, providing
      the potential for a durable response following a single, self-limited treatment.
      This perspective drives the efforts to make this protocol accessible for more
      patients and to explore modifications that may optimize treatment results.

PMID- 22864562
TI  - Identification of Hortaea werneckii Isolated from mangrove plant Aegiceras
      comiculatum based on morphology and rDNA sequences.
AB  - Hortaea werneckii is a black yeast-like ascomycetous fungi associated with the
      human superficial infection tinea nigra, which commonly occurs in tropical and
      subtropical countries. Now, this fungus has been found in the halophilic
      environment all over the world and recognized as a new model organism in
      exploring the mechanisms of salt tolerance in eukaryotes. During a survey of
      endophytic fungi of mangrove forest at South China Sea, two isolates of H.
      werneckii were recovered from medicinal plant of Aegiceras comiculatum. The
      isolates were identified by morphological characters and phylogenetic analyses
      (e.g., ITS rDNA, LSU rDNA and translation elongation factor EF1alpha). Some
      physiological tests such as thermotolerance, acid tolerance (pH) and NaCl
      tolerance as well as pathogenicity test in vitro for the strains of Hortaea were
      performed. It is the first report that H. werneckii was isolated from medicinal
      plant of A. comiculatum in south sea of China as the endophytic fungi.

PMID- 22864563
TI  - Drosophila innate immune response pathways moonlight in neurodegeneration.
AB  - In this Extra View, we highlight recent Drosophila research that has uncovered a
      new role for the innate immune response. The research indicates that, in addition
      to combating infection, the innate immune response promotes neurodegeneration.
      Our publication (Petersen et al., 2012) reveals a correlative relationship
      between the innate immune response and neurodegeneration in a model of the human
      disease Ataxia-telangiectasia (A-T). We also found that glial cells are
      responsible for the innate immune response in the A-T model, and work by others
      implicates glial cells in neurodegeneration. Additionally, publications by
      Chinchore et al. (2012) and Tan et al. (2008) reveal a causative role for the
      innate immune response in models of human retinal degenerative disorders and
      Alzheimer disease, respectively. Collectively, these findings suggest that
      activation of the innate immune response is a shared cause of neurodegeneration
      in different human diseases.

PMID- 22864564
TI  - Patient's anxiety and fear of anesthesia: effect of gender, age, education, and
      previous experience of anesthesia. A survey of 400 patients.
AB  - PURPOSE: Patients express high anxiety preoperatively, because of fears related
      to anesthesia and its implications. The purpose of this survey was to gain
      insight into these fears and to study whether they are affected by patients' sex,
      age, education, or previous experience of anesthesia. METHODS: Questionnaires
      with fixed questions were distributed to consenting, consecutive surgical
      patients before the pre-anesthetic visit. The questionnaires included patients'
      demographics and questions related to their fears about anesthesia. RESULTS: Four
      hundred questionnaires were collected and analyzed. Eighty-one percent of
      patients experience preoperative anxiety. The main sources of their anxiety were
      fear of postoperative pain (84 %), of not waking up after surgery (64.8 %), of
      being nauseous or vomiting (60.2 %), and of drains and needles (59.5 %). Patients
      are less concerned about being paralyzed because of anesthesia (33.5 %) or of
      revealing personal issues (18.8 %). Gender seems to affect patients fears, with
      women being more afraid (85.3 vs. 75.6 % of men, p = 0.014). The effects of
      patients' age, level of education, and previous experience of anesthesia are
      minor, except for individual questions. Sixty-three percent of our patients
      (mostly women 67.4 vs. 57.4 % of men, p = 0.039) talk about these fears with
      their relatives, although a vast majority of 95.5 % would prefer to talk with the
      anesthesiologist and be reassured by him. CONCLUSION: All patients, mostly women,
      express fears about anesthesia; this fear leads to preoperative anxiety. Slight
      differences are observed for some individual questions among patients of
      different sex, education level, and previous experience of anesthesia.

PMID- 22864565
TI  - Analysis of HIV/AIDS DRG in Portugal: a hierarchical finite mixture model.
AB  - Inpatient length of stay (LOS) is an important measure of hospital activity, but
      its empirical distribution is often positively skewed, representing a challenge
      for statistical analysis. Taking this feature into account, we seek to identify
      factors that are associated with HIV/AIDS through a hierarchical finite mixture
      model. A mixture of normal components is applied to adult HIV/AIDS diagnosis
      related group data (DRG) from 2008. The model accounts for the demographic and
      clinical characteristics of the patients, as well the inherent correlation of
      patients clustered within hospitals. In the present research, a normal mixture
      distribution was fitted to the logarithm of LOS and it was found that a model
      with two-components had the best fit, resulting in two subgroups of LOS: a short
      stay subgroup and a long-stay subgroup. Associated risk factors for both groups
      were identified as well as some statistical differences in the hospitals. Our
      findings provide important information for policy makers in terms of discharge
      planning and the efficient management of LOS. The presence of "atypical"
      hospitals also suggests that hospitals should not be viewed or treated as
      homogenous bodies. 

PMID- 22864566
TI  - Surgical and anesthesia capacity in Bolivian public hospitals: results from a
      national hospital survey.
AB  - BACKGROUND: Underdeveloped nations suffer from significant deficiencies in
      surgical and anesthesia care. Although surgical inequities are a pressing issue
      internationally, the extent of these inequities is unknown due to a lack of data.
      The aim of this study was to assess surgical and anesthesia capacity in Bolivia
      as part of a multinational study assessing surgical and anesthesia infrastructure
      in Africa, Latin America, and South Asia. METHODS: A standardized survey tool was
      used to obtain national-level health-care data at the Bolivian Ministry of
      Health. Hospital-specific data were obtained through interviews with key
      administrators and providers at 18 public basic and general hospitals in Bolivia.
      RESULTS: There are 1,270 obstetrician/gynecologists and 1,807 surgeons in
      Bolivia. In contrast, there are 500 anesthesiologists, placing a large anesthesia
      burden on the country. Basic hospitals and general hospitals performed an average
      of 730 and 2,858 operations per year, respectively. One basic hospital was unable
      to perform any surgeries due to a lack of surgical manpower. All but two
      hospitals reported some lack of infrastructure, equipment, or pharmaceutical
      capacity. The ability to collect health outcomes was inconsistent in most
      hospitals. CONCLUSIONS: Surgical capacity varies throughout Bolivia. There are
      relatively large numbers of surgery providers but an insufficient number of
      anesthesiologists, suggesting a specific need for further development in
      anesthesia. Though there are many areas of strength within the Bolivian public
      health-care system, this survey identified several areas to which national policy
      and international collaboration can contribute in order to more adequately
      address major causes of surgical morbidity and mortality.

PMID- 22864567
TI  - Management of spontaneously ruptured hepatocellular carcinoma and hemoperitoneum
      manifested as acute abdomen in the emergency room.
AB  - BACKGROUND: Spontaneously ruptured hepatocellular carcinoma (HCC) with
      hemoperitoneum has a poor prognosis, especially in cases of cirrhosis. Patients
      usually present to emergency rooms (ERs) with acute abdomen. The aim of the
      present study was to determine the factors affecting mortality and to compare the
      prognosis of conservative treatment, transcatheter arterial embolization (TAE),
      or hepatectomy in these situations. METHODS: Fifty-four patients with
      spontaneously ruptured HCC diagnosed between January 2004 and August 2010 were
      enrolled in this retrospective review of clinical data. Grouping by survival or
      mortality, univariate and multivariate analyses of factors affecting 30-day
      mortality, and long-term survival were conducted. The outcomes of the various
      treatments were analyzed. RESULTS: After primary fluid resuscitation in the ER, 6
      of 54 patients underwent conservative treatment. Emergency hepatectomy was
      performed on 19 patients; TAE was used for 29 patients, 18 of whom received
      staged hepatectomy thereafter. Poor liver function, prolonged international
      normalized ratio (INR), and conservative treatment were associated with increased
      30-day mortality. Logistic regression analysis of cumulative survival revealed
      that INR >= 1.4, multiple intrahepatic HCC, and conservative treatment were
      related to poorer long-term survival. The patients who received hepatectomy,
      either immediate or staged after TAE, had higher survival rates of 85.2 % at 30
      days and 62.2 % at 1 year. CONCLUSIONS: The treatment of ruptured HCC should be
      tailored to the individual case. Prolonged survival is possible in patients with
      preserved liver function through curative liver resection. Emergency physicians,
      radiologists, and surgeons play essential roles in managing these patients.

PMID- 22864568
TI  - Ischemic pseudotumor of the colon: an insidious form of ischemic colitis.

PMID- 22864569
TI  - Proteomic screen reveals Fbw7 as a modulator of the NF-kappaB pathway.
AB  - Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but
      the full range of Fbw7 substrates is not known. Here we show that by performing
      quantitative proteomics combined with degron motif searches, we effectively
      screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7
      substrates, including several disease-associated proteins. The transcription
      factor NF-kappaB2 (p100/p52) is one of the candidate Fbw7 substrates. We show
      that Fbw7 interacts with p100 via a conserved degron and that it promotes
      degradation of p100 in a GSK3beta phosphorylation-dependent manner. Fbw7
      inactivation increases p100 levels, which in the presence of NF-kappaB pathway
      stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic
      threshold can be increased by loss of Fbw7 in a p100-dependent manner. In
      conclusion, Fbw7-mediated destruction of p100 is a regulatory component
      restricting the response to NF-kappaB2 pathway stimulation.

PMID- 22864570
TI  - Solderable and electroplatable flexible electronic circuit on a porous
      stretchable elastomer.
AB  - A variety of flexible and stretchable electronics have been reported for use in
      flexible electronic devices or biomedical applications. The practical and wider
      application of such flexible electronics has been limited because commercial
      electronic components are difficult to be directly integrated into flexible
      stretchable electronics and electroplating is still challenging. Here, we propose
      a novel method for fabricating flexible and stretchable electronic devices using
      a porous elastomeric substrate. Pressurized steam was applied to an uncured
      polydimethylsiloxane layer for the simple and cost-effective production of porous
      structure. An electroplated nickel anchor had a key role in bonding commercial
      electronic components on elastomers by soldering techniques, and metals could be
      stably patterned and electroplated for practical uses. The proposed technology
      was applied to develop a plaster electrocardiogram dry electrode and multi
      channel microelectrodes that could be used as a long-term wearable biosignal
      monitor and for brain signal monitoring, respectively.

PMID- 22864571
TI  - Ubiquitination and degradation of the FADD adaptor protein regulate death
      receptor-mediated apoptosis and necroptosis.
AB  - Fas-associated protein with death domain (FADD) is a pivotal component of death
      receptor-mediated extrinsic apoptosis and necroptosis. Here we show that FADD is
      regulated by Makorin Ring Finger Protein 1 (MKRN1) E3 ligase-mediated
      ubiquitination and proteasomal degradation. MKRN1 knockdown results in FADD
      protein stabilization and formation of the rapid death-inducing signalling
      complex, which causes hypersensitivity to extrinsic apoptosis by facilitating
      caspase-8 and caspase-3 cleavage in response to death signals. We also show that
      MKRN1 and FADD are involved in the regulation of necrosome formation and
      necroptosis upon caspase inhibition. Downregulation of MKRN1 results in severe
      defects of tumour growth upon tumour necrosis factor-related apoptosis-inducing
      ligand treatment in a xenograft model using MDA-MB-231 breast cancer cells.
      Suppression of tumour growth by MKRN1 depletion is relieved by simultaneous FADD
      knockdown. Our data reveal a novel mechanism by which fas-associated protein with
      death domain is regulated via an ubiquitination-induced degradation pathway.

PMID- 22864572
TI  - Quantifying the magnetic nature of light emission.
AB  - Tremendous advances in the study of magnetic light-matter interactions have
      recently been achieved using man-made nanostructures that exhibit and exploit an
      optical magnetic response. However, naturally occurring emitters can also exhibit
      magnetic resonances in the form of optical-frequency magnetic-dipole transitions.
      Here we quantify the magnetic nature of light emission using energy- and momentum
      resolved spectroscopy, and leverage a pair of spectrally close electric- and
      magnetic-dipole transitions in trivalent europium to probe vacuum fluctuations in
      the electric and magnetic fields at the nanometre scale. These results reveal a
      new tool for nano-optics: an atomic-size quantum emitter that interacts with the
      magnetic component of light.

PMID- 22864573
TI  - Social networks reveal cultural behaviour in tool-using [corrected] dolphins.
AB  - Animal tool use is of inherent interest given its relationship to intelligence,
      innovation and cultural behaviour. Here we investigate whether Shark Bay
      bottlenose dolphins that use marine sponges as hunting tools (spongers) are
      culturally distinct from other dolphins in the population based on the criteria
      that sponging is both socially learned and distinguishes between groups. We use
      social network analysis to determine social preferences among 36 spongers and 69
      non-spongers sampled over a 22-year period while controlling for location, sex
      and matrilineal relatedness. Homophily (the tendency to associate with similar
      others) based on tool-using status was evident in every analysis, although
      maternal kinship, sex and location also contributed to social preference. Female
      spongers were more cliquish and preferentially associated with other spongers
      over non-spongers. Like humans who preferentially associate with others who share
      their subculture, tool-using dolphins prefer others like themselves, strongly
      suggesting that sponge tool-use is a cultural behaviour.

PMID- 22864574
TI  - An orbital-selective spin liquid in a frustrated heavy fermion spinel LiV2O4.
AB  - The pronounced enhancement of the effective mass is the primary phenomenon
      associated with strongly correlated electrons. In the presence of local moments,
      the large effective mass is thought to arise from Kondo coupling, the interaction
      between itinerant and localized electrons. However, in d electron systems, the
      origin is not clear because of the competing Hund's rule coupling. Here we
      experimentally address the microscopic origin for the heaviest d fermion in a
      vanadium spinel LiV(2)O(4) having geometrical frustration. Utilizing orbital
      selective (51)V NMR, we elucidate the orbital-dependent local moment that
      exhibits no long-range magnetic order despite persistent antiferromagnetic
      correlations. A frustrated spin liquid, Hund-coupled to itinerant electrons, has
      a crucial role in forming heavy fermions with large residual entropy. Our method
      is important for the microscopic observation of the orbital-selective
      localization in a wide range of materials including iron pnictides, cobaltates,
      manganites and ruthnates.

PMID- 22864575
TI  - Topological crystalline insulators in the SnTe material class.
AB  - Topological crystalline insulators are new states of matter in which the
      topological nature of electronic structures arises from crystal symmetries. Here
      we predict the first material realization of topological crystalline insulator in
      the semiconductor SnTe by identifying its non-zero topological index. We predict
      that as a manifestation of this non-trivial topology, SnTe has metallic surface
      states with an even number of Dirac cones on high-symmetry crystal surfaces such
      as {001}, {110} and {111}. These surface states form a new type of high-mobility
      chiral electron gas, which is robust against disorder and topologically protected
      by reflection symmetry of the crystal with respect to {110} mirror plane.
      Breaking this mirror symmetry via elastic strain engineering or applying an in
      plane magnetic field can open up a continuously tunable band gap on the surface,
      which may lead to wide-ranging applications in thermoelectrics, infra-red
      detection and tunable electronics. Closely related semiconductors PbTe and PbSe
      also become topological crystalline insulators after band inversion by pressure,
      strain and alloying.

PMID- 22864576
TI  - Symmetry breaking in the formation of magnetic vortex states in a permalloy
      nanodisk.
AB  - The magnetic vortex in nanopatterned elements is currently attracting enormous
      interest. A priori, one would assume that the formation of magnetic vortex states
      should exhibit a perfect symmetry, because the magnetic vortex has four
      degenerate states. Here we show the first direct observation of an asymmetric
      phenomenon in the formation process of vortex states in a permalloy nanodisk
      using high-resolution full-field magnetic transmission soft X-ray microscopy.
      Micromagnetic simulations confirm that the intrinsic Dzyaloshinskii-Moriya
      interaction, which arises from the spin-orbit coupling due to the lack of
      inversion symmetry near the disk surface, as well as surface-related extrinsic
      factors, is decisive for the asymmetric formation of vortex states.

PMID- 22864577
TI  - Photo-actuation of liquids for light-driven microfluidics: state of the art and
      perspectives.
AB  - Using light to control liquid motion is a new paradigm for the actuation of
      microfluidic systems. We review here the different principles and strategies to
      induce or control liquid motion using light, which includes the use of radiation
      pressure, optical tweezers, light-induced wettability gradients, the
      thermocapillary effect, photosensitive surfactants, the chromocapillary effect,
      optoelectrowetting, photocontrolled electroosmotic flows and optical
      dielectrophoresis. We analyze the performance of these approaches to control
      using light many kinds of microfluidic operations involving discrete pL- to MUL
      sized droplets (generation, driving, mixing, reaction, sorting) or fluid flows in
      microchannels (valve operation, injection, pumping, flow rate control). We show
      that a complete toolbox is now available to control microfluidic systems by
      light. We finally discuss the perspectives of digital optofluidics as well as
      microfluidics based on all optical fluidic chips and optically reconfigurable
      devices.

PMID- 22864578
TI  - Chemometric characterization of river water quality.
AB  - Various industrial facilities in the city of Varanasi discharge their effluent
      mixed with municipal sewage into the River Ganges at different discharge points.
      In this study, chemometric tools such as cluster analysis and box-whisker plots
      were applied to interpret data obtained during examination of River Ganges water
      quality. Specifically, we investigated the temperature (T), pH, total alkalinity,
      total acidity, electrical conductivity (EC), biochemical oxygen demand (BOD),
      chemical oxygen demand (COD), dissolved oxygen (DO), nitrate nitrogen (N),
      phosphate (PO 4(2-) ), copper (Cu), cadmium (Cd), chromium (Cr), nickel (Ni),
      iron (Fe), lead (Pb), and zinc (Zn) in water samples collected from six sampling
      stations. Hierarchical agglomerative cluster analysis was conducted using Ward's
      method. Proximity distance between EC and Cr was the smallest revealing a
      relationship between these parameters, which was confirmed by Pearson's
      correlation. Based on proximity distances, EC, Cr, Ni, Fe, N, COD, temperature,
      BOD, and total acidity comprised one group; Zn, Pb, Cd, total alkalinity, Cu, and
      phosphate (PO 4(2-) ) were in another group; and DO and pH formed a separate
      group. These groups were confirmed by Pearson's correlation (r) values that
      indicated significant and positive correlation between variables in the same
      group. Box-whisker plots revealed that as we go downstream, the pollutant
      concentration increases and maximum at the downstream station Raj Ghat and
      minimum at the upstream station Samane Ghat. Seasonal variations in water quality
      parameters signified that total alkalinity, total acidity, DO, BOD, COD, N,
      phosphate (PO 4(2-) ), Cu, Cd, Cr, Ni, Fe, Pb, and Zn were the highest in summer
      (March-June) and the lowest during monsoon season (July-October). Temperature was
      the highest in summer and the lowest in winter (November-February). DO was the
      highest in winter and the lowest in summer season. pH was observed to be the
      highest in monsoon and the lowest in summer season.

PMID- 22864579
TI  - Assessing and monitoring semi-arid shrublands using object-based image analysis
      and multiple endmember spectral mixture analysis.
AB  - Arid and semi-arid shrublands have significant biological and economical values
      and have been experiencing dramatic changes due to human activities. In
      California, California sage scrub (CSS) is one of the most endangered plant
      communities in the US and requires close monitoring in order to conserve this
      important biological resource. We investigate the utility of remote-sensing
      approaches--object-based image analysis applied to pansharpened QuickBird imagery
      (QBPS/OBIA) and multiple endmember spectral mixture analysis (MESMA) applied to
      SPOT imagery (SPOT/MESMA)--for estimating fractional cover of true shrub,
      subshrub, herb, and bare ground within CSS communities of southern California. We
      also explore the effectiveness of life-form cover maps for assessing CSS
      conditions. Overall and combined shrub cover (i.e., true shrub and subshrub) were
      estimated more accurately using QBPS/OBIA (mean absolute error or MAE, 8.9 %)
      than SPOT/MESMA (MAE, 11.4 %). Life-form cover from QBPS/OBIA at a 25 * 25 m grid
      cell size seems most desirable for assessing CSS because of its higher accuracy
      and spatial detail in cover estimates and amenability to extracting other
      vegetation information (e.g., size, shape, and density of shrub patches). Maps
      derived from SPOT/MESMA at a 50 * 50 m scale are effective for retrospective
      analysis of life-form cover change because their comparable accuracies to
      QBPS/OBIA and availability of SPOT archives data dating back to the mid-1980s.
      The framework in this study can be applied to other physiognomically comparable
      shrubland communities.

PMID- 22864580
TI  - Towards a sampling strategy for the assessment of forest condition at European
      level: combining country estimates.
AB  - A correct characterization of the status and trend of forest condition is
      essential to support reporting processes at national and international level. An
      international forest condition monitoring has been implemented in Europe since
      1987 under the auspices of the International Co-operative Programme on Assessment
      and Monitoring of Air Pollution Effects on Forests (ICP Forests). The monitoring
      is based on harmonized methodologies, with individual countries being responsible
      for its implementation. Due to inconsistencies and problems in sampling design,
      however, the ICP Forests network is not able to produce reliable quantitative
      estimates of forest condition at European and sometimes at country level. This
      paper proposes (1) a set of requirements for status and change assessment and (2)
      a harmonized sampling strategy able to provide unbiased and consistent estimators
      of forest condition parameters and of their changes at both country and European
      level. Under the assumption that a common definition of forest holds among
      European countries, monitoring objectives, parameters of concern and accuracy
      indexes are stated. On the basis of fixed-area plot sampling performed
      independently in each country, an unbiased and consistent estimator of forest
      defoliation indexes is obtained at both country and European level, together with
      conservative estimators of their sampling variance and power in the detection of
      changes. The strategy adopts a probabilistic sampling scheme based on fixed-area
      plots selected by means of systematic or stratified schemes. Operative guidelines
      for its application are provided.

PMID- 22864581
TI  - No relationship found between mercury and lead concentrations in muscle and
      scales of chub Squalius cephalus L.
AB  - We examined the relationship between muscle and scale mercury (Hg) and lead (Pb)
      concentrations in chub Squalius cephalus L. from six riverine sites in the Czech
      Republic in order to determine whether scale analysis alone could provide a
      nonlethal and convenient method for prediction of heavy metal concentration in
      muscle tissue. Our results confirm tissue-specific heavy metal accumulation in
      chub, with Hg tending to accumulate primarily in muscle tissue and Pb in scales.
      We found no significant relationship, however, for concentrations of either Pb or
      Hg between muscle tissue and scales of chub. Our results indicate that scales
      cannot be used for predicting heavy metal contamination in muscle of chub and we
      recommend, therefore, that muscle biopsy methods continue as the preferred method
      of analysis.

PMID- 22864582
TI  - New insights into roles of cell wall invertase in early seed development revealed
      by comprehensive spatial and temporal expression patterns of GhCWIN1 in cotton.
AB  - Despite substantial evidence on the essential roles of cell wall invertase (CWIN)
      in seed filling, it remains largely unknown how CWIN exerts its regulation early
      in seed development, a critical stage that sets yield potential. To fill this
      knowledge gap, we systematically examined the spatial and temporal expression
      patterns of a major CWIN gene, GhCWIN1, in cotton (Gossypium hirsutum) seeds from
      prefertilization to prestorage phase. GhCWIN1 messenger RNA was abundant at the
      innermost seed coat cell layer at 5 d after anthesis but became undetectable at
      10 d after anthesis, at the onset of its differentiation into transfer cells
      characterized by wall ingrowths, suggesting that CWIN may negatively regulate
      transfer cell differentiation. Within the filial tissues, GhCWIN1 transcript was
      detected in endosperm cells undergoing nuclear division but not in those cells at
      the cellularization stage, with similar results observed in Arabidopsis
      (Arabidopsis thaliana) endosperm for CWIN, AtCWIN4. These findings indicate a
      function of CWIN in nuclear division but not cell wall biosynthesis in endosperm,
      contrasting to the role proposed for sucrose synthase (Sus). Further analyses
      revealed a preferential expression pattern of GhCWIN1 and AtCWIN4 in the
      provascular region of the torpedo embryos in cotton and Arabidopsis seed,
      respectively, indicating a role of CWIN in vascular initiation. Together, these
      novel findings provide insights into the roles of CWIN in regulating early seed
      development spatially and temporally. By comparing with previous studies on Sus
      expression and in conjunction with the expression of other related genes, we
      propose models of CWIN- and Sus-mediated regulation of early seed development.

PMID- 22864583
TI  - Lotus japonicus ARPC1 is required for rhizobial infection.
AB  - Remodeling of the plant cell cytoskeleton precedes symbiotic entry of nitrogen
      fixing bacteria within the host plant roots. Here we identify a Lotus japonicus
      gene encoding a predicted ACTIN-RELATED PROTEIN COMPONENT1 (ARPC1) as essential
      for rhizobial infection but not for arbuscular mycorrhiza symbiosis. In other
      organisms ARPC1 constitutes a subunit of the ARP2/3 complex, the major nucleator
      of Y-branched actin filaments. The L. japonicus arpc1 mutant showed a distorted
      trichome phenotype and was defective in epidermal infection thread formation,
      producing mostly empty nodules. A few partially colonized nodules that did form
      in arpc1 contained abnormal infections. Together with previously described L.
      japonicus Nck-associated protein1 and 121F-specific p53 inducible RNA mutants,
      which are also impaired in the accommodation of rhizobia, our data indicate that
      ARPC1 and, by inference a suppressor of cAMP receptor/WASP-family verpolin
      homologous protein-ARP2/3 pathway, must have been coopted during evolution of
      nitrogen-fixing symbiosis to specifically mediate bacterial entry.

PMID- 22864584
TI  - Diffusion limitations in root uptake of cadmium and zinc, but not nickel, and
      resulting bias in the Michaelis constant.
AB  - It has long been recognized that diffusive boundary layers affect the
      determination of active transport parameters, but this has been largely
      overlooked in plant physiological research. We studied the short-term uptake of
      cadmium (Cd), zinc (Zn), and nickel (Ni) by spinach (Spinacia oleracea) and
      tomato (Lycopersicon esculentum) in solutions with or without metal complexes. At
      same free ion concentration, the presence of complexes, which enhance the
      diffusion flux, increased the uptake of Cd and Zn, whereas Ni uptake was
      unaffected. Competition effects of protons on Cd and Zn uptake were observed only
      at a very large degree of buffering, while competition of magnesium ions on Ni
      uptake was observed even in unbuffered solutions. These results strongly suggest
      that uptake of Cd and Zn is limited by diffusion of the free ion to the roots,
      except at very high degree of solution buffering, whereas Ni uptake is generally
      internalization limited. All results could be well described by a model that
      combined a diffusion equation with a competitive Michaelis-Menten equation.
      Direct uptake of the complex was estimated to be a major contribution only at
      millimolar concentrations of the complex or at very large ratios of complex to
      free ion concentration. The true K(m) for uptake of Cd(2+) and Zn(2+) was
      estimated at <5 nm, three orders of magnitude smaller than the K(m) measured in
      unbuffered solutions. Published Michaelis constants for plant uptake of Cd and Zn
      likely strongly overestimate physiological ones and should not be interpreted as
      an indicator of transporter affinity.

PMID- 22864586
TI  - Mercury in wing and tail feathers of hatch-year and adult tidal marsh sparrows.
AB  - We estimated mercury exposure and bioaccumulation in sparrow feathers to
      determine variation among age groups, between sparrow species, and between
      feather types. Results of feather mercury studies in piscivorous birds indicate
      that mercury concentrations tend to increase with age and differ between feather
      types; however, data for insectivorous birds are lacking. We estimated mercury
      exposure of two insectivorous and sympatric tidal marsh sparrows: coastal plain
      swamp sparrow (Melospiza georgiana nigrescens), and seaside sparrow (Ammodramous
      maritimus). Tidal marshes have favorable conditions for mercury methlyation, thus
      it is likely that tidal marsh sparrows are exposed to methylmercury. We found no
      difference in mercury concentrations between males and female birds of both
      species. Adult swamp sparrow feather mercury concentrations did not differ among
      adult age groups; therefore, mercury was not found to increase with age in
      sparrows at the site. Hatch-year birds had significantly greater feather mercury
      concentrations compared with adult birds for both species. Mercury concentrations
      in adult seaside sparrows were twice as high as those in adult swamp sparrows
      suggesting species-specific variation, although concentrations in hatch-year
      sparrow species did not differ. Mercury concentrations differed between feather
      types in adults of both species. The first primary feather of both species had at
      least three times greater mercury concentrations than the outer tail feather
      possibly reflecting varying depuration rates with feather type.

PMID- 22864585
TI  - A land-plant-specific glycerol-3-phosphate acyltransferase family in Arabidopsis:
      substrate specificity, sn-2 preference, and evolution.
AB  - Arabidopsis (Arabidopsis thaliana) has eight glycerol-3-phosphate acyltransferase
      (GPAT) genes that are members of a plant-specific family with three distinct
      clades. Several of these GPATs are required for the synthesis of cutin or
      suberin. Unlike GPATs with sn-1 regiospecificity involved in membrane or storage
      lipid synthesis, GPAT4 and -6 are unique bifunctional enzymes with both sn-2
      acyltransferase and phosphatase activity resulting in 2-monoacylglycerol
      products. We present enzymology, pathway organization, and evolutionary analysis
      of this GPAT family. Within the cutin-associated clade, GPAT8 is demonstrated as
      a bifunctional sn-2 acyltransferase/phosphatase. GPAT4, -6, and -8 strongly
      prefer C16:0 and C18:1 omega-oxidized acyl-coenzyme As (CoAs) over unmodified or
      longer acyl chain substrates. In contrast, suberin-associated GPAT5 can
      accommodate a broad chain length range of omega-oxidized and unsubstituted acyl
      CoAs. These substrate specificities (1) strongly support polyester biosynthetic
      pathways in which acyl transfer to glycerol occurs after oxidation of the acyl
      group, (2) implicate GPAT specificities as one major determinant of cutin and
      suberin composition, and (3) argue against a role of sn-2-GPATs (Enzyme
      Commission 2.3.1.198) in membrane/storage lipid synthesis. Evidence is presented
      that GPAT7 is induced by wounding, produces suberin-like monomers when
      overexpressed, and likely functions in suberin biosynthesis. Within the third
      clade, we demonstrate that GPAT1 possesses sn-2 acyltransferase but not
      phosphatase activity and can utilize dicarboxylic acyl-CoA substrates. Thus, sn-2
      acyltransferase activity extends to all subbranches of the Arabidopsis GPAT
      family. Phylogenetic analyses of this family indicate that GPAT4/6/8 arose early
      in land-plant evolution (bryophytes), whereas the phosphatase-minus GPAT1 to -3
      and GPAT5/7 clades diverged later with the appearance of tracheophytes.

PMID- 22864587
TI  - Pyruvate kinase activity and delta-aminolevulinic acid dehydratase activity as
      biomarkers of toxicity in workers exposed to lead.
AB  - Lead (Pb(2+)) is a heavy metal that has long been used by humans for a wide range
      of technological purposes, which is the main reason for its current widespread
      distribution. Pb(2+) is thought to enter erythrocytes through anion exchange and
      to remain in the cell by binding to thiol groups. Pyruvate kinase (PK) is a thiol
      containing enzyme that plays a key role in erythrocyte cellular energy
      homeostasis. delta-aminolevulinic acid dehydratase (delta-ALAD) is the second
      enzyme in the heme biosynthetic pathway and plays a role in the pathogenesis of
      Pb poisoning. Our primary objective was to investigate the effect of Pb(2+) on
      the activity of the thiolenzymes delta-ALAD and PK and on the concentration of
      glutathione (GSH), a nonenzymatic antioxidant defense, in erythrocytes from Pb
      exposed workers. The study sample comprised 22 male Pb workers and 21 normal
      volunteers (15 men and 6 women). The Pb-exposed workers were employed in
      manufacturing and recycling of automotive batteries. Basic red-cell parameters
      were assayed and total white blood cell counts performed. PK and delta-ALAD
      activity and blood Pb (BPb) concentrations were determined in all subjects. Pb
      exposed individuals had significantly greater BPb levels than controls. Both PK
      and delta-ALAD activity levels were significantly lower in Pb-exposed individuals
      than in controls. Pb significantly inhibited PK and delta-ALAD activity in a dose
      dependent manner. We found that erythrocyte GSH levels were lower in Pb-exposed
      individuals than normal volunteers. Pb-exposed individuals had lower values than
      controls for several red cell parameters (hemoglobin, hematocrit, red blood cell
      count, mean corpuscular volume). These results suggest that Pb inhibits delta
      ALAD and PK activity by interacting with their thiol groups. It is therefore
      possible that Pb disrupts energy homeostasis and may be linked with decreased
      glucose metabolism because it affects the heme synthesis pathway in erythrocytes,
      contributing to the cell dysfunction observed in these in Pb-exposed individuals.
      These results indicate an apparent dose-effect relationship between PK activity
      and BPb. PK activity in human erythrocytes can be used for biological monitoring
      of Pb exposure. Study of the mechanisms by which Pb acts may contribute to
      greater understanding of the symptoms caused by Pb.

PMID- 22864588
TI  - Toxicity of metal-ethylenediaminetetraacetic acid solution as a function of
      chemical speciation: an approach for toxicity assessment.
AB  - The influence of complexation by ethylenediaminetetraacetic acid (EDTA) on the
      toxicity of Cd(II), Cu(II), Cd(II), and Ni(II) was investigated. Result of the
      Microtox test, which is based on measuring the decrease of light emitted by
      Vibrio fischeri bacterium when exposed to a toxicant, was used as an indication
      of toxicity. The effect of pH and EDTA molar ratio that might potentially modify
      the percentage of chemical species in solution on toxicity was evaluated. In
      general, results indicate that toxicity decreases when increasing the pH value as
      well as the EDTA molar ratio. Chemical modeling was used to predict metal
      speciation and correlation analysis to relate chemical species with the obtained
      toxicity results. The species that most contribute to toxicity resulted to be
      MeCl(+) (Me = metal), which is formed as a consequence of the presence of the
      bioassay medium (2 % NaCl). A model that predicts metal-solution toxicity by
      using the chemical species, which most contribute to toxicity is proposed as a
      useful tool for toxicity assessment in waters containing metal ions and EDTA.

PMID- 22864589
TI  - Noninvasive acoustic radiation force impulse (ARFI) elastography for assessing
      the severity of fibrosis in the post-operative patients with biliary atresia.
AB  - PURPOSE: Liver biopsy (LB) is still considered the "gold standard" for
      hepatological evaluation, but recently noninvasive methods have attempted to
      replace this invasive procedure. Recently, acoustic radiation force impulse
      (ARFI) imaging has been developed as a noninvasive modality to evaluate the
      stiffness of tissues. ARFI imaging theoretically measures liver stiffness of all
      the segments independently. The aim of this study was to determine whether ARFI
      elastography is a reliable method for predicting the severity of fibrosis in the
      post-operative patients with biliary atresia. METHODS: ARFI elastography was
      performed 21 times in eight patients with biliary atresia over the last 2 years.
      At the same time, we measured serum hyaluronic acid (H value), which is one of
      the serum elastic makers, to compare ARFI versus values in these patients. We
      obtained ARFI versus values as the median of S2 to S8 by three consecutive
      measurements acquired with a Siemens Acuson S2000 (Siemens Medical Systems,
      Germany). RESULTS: Histological evaluation of fibrosis is graded from F0 (normal)
      to F4. The normal H value is under 50 mg/dl. One patient had F0 (H value 29.2
      mg/dl), four had F1 (H value 11.5-18.1 mg/dl), one had F3 (H value 61.3 mg/dl),
      two had F4 (H value 29.2, 112 mg/dl). One patient with F4 whose ARFI versus value
      (3.56 m/s) was the highest, needed liver transplantation and her liver was
      cirrhotic. CONCLUSION: These findings suggest that ARFI measurement may be a
      reliable method for predicting the severity of fibrosis after a Kasai operation.

PMID- 22864590
TI  - Risk factors of infection of implanted device after the Nuss procedure.
AB  - PURPOSE: The Nuss procedure is a minimally invasive procedure for the correction
      of pectus excavatum. It involves insertion of a substernal metal bar. A feared
      complication of any implantation procedure is infection, which often requires
      removal of the implanted device. This report describes the authors' experience
      with infectious complications after the Nuss procedure. METHODS: The study
      included 195 patients diagnosed with pectus excavatum. We performed the Nuss
      procedure under thoracoscopic control on all the patients. Factors analyzed for
      all patients included bar infection, sex, age, number of bars, and season of the
      year during which the operation was performed. RESULTS: Of the 195 study
      patients, there were 11 patients who suffered postoperative infectious
      complications, including 7 patients with cellulitis and 4 patients with bar
      infections. We removed the infected bars from three of the patients with bar
      infections. Ten of the patients with infected bar had undergone their operations
      in the summer. Sex, age and number of bars did not differ significantly between
      patients with or without infections. However, a significantly higher number of
      infections occurred among patients who underwent the Nuss procedure in the summer
      compared with the other seasons of the year (P < 0.05, Kruskal-Wallis Test).
      CONCLUSION: All patients with cellulitis successfully recovered with conservative
      treatment. However, 75 % of the patients with bar infections required removal of
      the infected device. Our study results showed that performance of the Nuss
      procedure during summer is a risk factor for postoperative infection. We
      recommend that particularly careful technique must be used during summer to
      prevent postoperative infections following the Nuss procedure.

PMID- 22864591
TI  - Determination and dynamics of ethylicin residues in cotton-field ecosystem.
AB  - In this work, we developed an efficient method to determine the ethylicin content
      in soil, cotton plant and cotton seed, and we also studied the fate of ethylicin
      in the cotton field ecosystem. The residual ethylicin was analyzed by GC-ECD. The
      limit of quantification was 0.005 mg/kg for soil, 0.01 mg/kg for the plant and
      cotton seed. The kinetics study of ethylicin residue showed that the ethylicin
      concentration in plant and soil can be regressively quantified as C = 1.0762e(
      0.2529t) and C = 0.5535e(-0.1333t), representing a half-live of 2.7 and 5.2 days,
      respectively. As a conclusion, a dosage of 354 g a.i. ha(-1) was recommended,
      which could be considered as safe to human beings and animals.

PMID- 22864592
TI  - Red fox (Vulpes vulpes Linnaeus, 1758) as biological indicator for environmental
      pollution in Hungary.
AB  - Our aim were to establish the metal (Cu, Ni, Zn, Co, Cd, and Pb) levels of red
      fox liver and the kidney samples (n = 10) deriving from central part of Hungary
      and compare the results with other countries' data. According to our results the
      concentrations of residues of the targeted elements (mg/kg dry weight) in liver
      and kidney samples were, respectively in liver: Cu: 21.418, Zn: 156.928, Ni:
      2.079, Co: 1.611, Pb: 1.678 and Cd: 0.499; and kidney samples: Cu: 9.236; Zn:
      87.159; Ni: 2.514; Co: 2.455; Pb: 2.63 and Cd: 0.818. Pb levels of Hungarian red
      fox liver samples significantly exceed the values of Italian specimens' samples,
      whilst the same element's concentrations of Hungarian red fox kidney samples were
      higher than the results published in Germany.

PMID- 22864594
TI  - Alfalfa nodules elicited by a flavodoxin-overexpressing Ensifer meliloti strain
      display nitrogen-fixing activity with enhanced tolerance to salinity stress.
AB  - Nitrogen fixation by legumes is very sensitive to salinity stress, which can
      severely reduce the productivity of legume crops and their soil-enriching
      capacity. Salinity is known to cause oxidative stress in the nodule by generating
      reactive oxygen species (ROS). Flavodoxins are involved in the response to
      oxidative stress in bacteria and cyanobacteria. Prevention of ROS production by
      flavodoxin overexpression in bacteroids might lead to a protective effect on
      nodule functioning under salinity stress. Tolerance to salinity stress was
      evaluated in alfalfa nodules elicited by an Ensifer meliloti strain that
      overexpressed a cyanobacterial flavodoxin compared with nodules produced by the
      wild-type bacteria. Nitrogen fixation, antioxidant and carbon metabolism enzyme
      activities were determined. The decline in nitrogenase activity associated to
      salinity stress was significantly less in flavodoxin-expressing than in wild-type
      nodules. We detected small but significant changes in nodule antioxidant
      metabolism involving the ascorbate-glutathione cycle enzymes and metabolites, as
      well as differences in activity of the carbon metabolism enzyme sucrose synthase,
      and an atypical starch accumulation pattern in flavodoxin-containing nodules.
      Salt-induced structural and ultrastructural alterations were examined in detail
      in alfalfa wild-type nodules by light and electron microscopy and compared to
      flavodoxin-containing nodules. Flavodoxin reduced salt-induced structural damage,
      which primarily affected young infected tissues and not fully differentiated
      bacteroids. The results indicate that overexpression of flavodoxin in bacteroids
      has a protective effect on the function and structure of alfalfa nodules
      subjected to salinity stress conditions. Putative protection mechanisms are
      discussed.

PMID- 22864595
TI  - Impact of disease frequency and host density on pollination and transmission of
      an African anther-smut fungus.
AB  - The vast majority of flowering plants rely solely on insects for pollination. A
      number of pathogens have evolved mechanisms to exploit these close associations
      and use pollinators as vectors of infective propagules. Factors that affect
      pollinator movements and successful pollination may in turn also influence
      successful transmission of fungal spores. Here we investigate the effect of host
      density and the frequency of diseased Oxalis lanata individuals infected by the
      anther-smut fungus, Thecaphora capensis, on the likelihood of receiving pollen
      and fungal spores. Specifically, we determined the numbers of spores and pollen
      grains deposited on stigmatic surfaces of selected flowers under natural and
      standardized conditions where host density and disease frequency varied. The
      effect of host flower density and diseased flower frequency on pollen and spore
      transfer was variable under natural conditions and these factors interacted
      significantly. However, an increase in host density and disease frequency
      significantly influenced pollen and spore deposits under standardized conditions.
      The effect of host density was, however, not linear and an optimal flower density
      for pollen and fungal spore transmission was found. Similar to other systems of
      vector-borne disease, the transmission of anther-smut of Oxalis lanata is more
      frequency-dependent than density-dependent. This study represents a first step
      towards understanding the disease transmission process of T. capensis on Oxalis
      and lays the foundation for future comparative studies between this and other
      systems to develop and test general hypotheses of disease dynamics in vector
      borne disease transmission systems.

PMID- 22864596
TI  - Assembly and properties of transition-metal coordination polymers based on semi
      rigid bis-pyridyl-bis-amide ligand: effect of polycarboxylates on the
      dimensionality.
AB  - Seven new coordination polymers, [Co(3-bpcd)(1,3-BDC)(H(2)O)(3)].H(2)O (1), [Co(3
      bpcd)(1,2-BDC)(H(2)O)].H(2)O (2), [Co(3)(3-bpcd)(1,2,4-BTC)(2)(H(2)O)(4)].4H(2)O
      (3), [Co(3-bpcd)(NPH)].2H(2)O (4), [Cu(3-bpcd)(1,3-BDC)] (5), [Cu(3-bpcd)(1,2
      BDC)] (6), [Cu(3-bpcd)(1,3,5-HBTC)(H(2)O)](2).2H(2)O (7) (3-bpcd = N,N'
      bis(pyridin-3-yl)cyclohexane-1,4-dicarboxamide, 1,3-H(2)BDC = 1,3
      benzenedicarboxylic acid, 1,2-H(2)BDC = 1,2-benzenedicarboxylic acid, 1,2,4
      H(3)BTC = 1,2,4-benzenetricarboxylic acid, H(2)NPH = 3-nitrophthalic acid and
      1,3,5-H(3)BTC = 1,3,5-benzenetricarboxylic acid) have been hydrothermally
      synthesized by assembling transition-metal cobalt-copper salts with semi-rigid
      bis-pyridyl-bis-amide ligand 3-bpcd and different aromatic polycarboxylic acids.
      Complex 1 exhibits a one-dimensional (1D) sinusoidal-like chain, which is further
      assembled into a three-dimensional (3D) supramolecular framework through hydrogen
      bonding interactions. Complex possesses a 3D framework with 4-connected 6(6)
      topology, which contains a two-dimensional (2D) distorted asymmetric hexagonal
      grid. When 1,2,4-BTC is used in complex , a 3D framework with
      (6(3).8(2).10)(2)(6(5).8)(2)(8) topology is constructed. Complex 2 possesses a 3D
      framework with 4-connected 6(6) topology, which contains a two-dimensional (2D)
      distorted asymmetric hexagonal grid. When 1,2,4-BTC is used in complex 3, a 3D
      framework with (6(3).8(2).10)(2)(6(5).8)(2)(8) topology is constructed. Complex 4
      possesses a 3D framework with 4-connected 6(6) topology, which is similar to that
      of 2 except for containing a 2D symmetric hexagonal grid. When Co(II) ion is
      replaced by Cu(II) ion, the 3D framework of complex 5 with (4.6(2))(4.6(6).8(3))
      topology based on 3-bpcd and 1,3-BDC ligands is obtained. Complex 6 shows a 2D
      cross network consisting of a superposed Cu-3-bpcd 1D chain and 1,2-BDC, which is
      further expanded into a 3D supramolecular framework by hydrogen-bonding
      interactions. In complex 7, 1,3,5-HBTC is employed as the auxiliary ligand, and a
      3D supramolecular framework based on the undulated 2D layers is formed through pi
      pi stacking and hydrogen-bonding interactions. Both the metal ions and
      polycarboxylates play important roles in the construction of the title complexes.
      In addition, the electrochemical behaviors and the fluorescence properties of the
      seven complexes have been investigated.

PMID- 22864598
TI  - One problem is the risk of the next: a vote for early detection and preventive
      intervention of coexisting psychopathology.

PMID- 22864597
TI  - The relationship among smoking, sleep, and chronic rheumatic conditions commonly
      associated with pain in the National Health Interview Survey.
AB  - Chronic rheumatic conditions are typically characterized by chronic pain and are
      uniquely associated with increased rates of cigarette smoking and poor sleep
      quality. However, no study has examined the possible additive or interactive
      effects of these two health behaviors in individuals diagnosed with a chronic
      rheumatic condition. The goal of this study is to examine the relationship
      between cigarette smoking and sleep in a population sample of individuals
      diagnosed with a chronic rheumatic condition and related functional impairment.
      Cross sectional survey data was obtained from the 2007 National Health Interview
      Survey. Individuals diagnosed with a chronic rheumatic condition were more likely
      to be a former or current smoker compared to non-diagnosed individuals.
      Individuals with a chronic rheumatic condition were more likely to report <6 h of
      sleep per night and endorsed significantly more insomnia and daytime sleepiness.
      There was no interaction between diagnosis of a chronic rheumatic condition and
      smoking status on any of the sleep outcomes assessed. Finally, an interaction was
      observed suggesting individuals with a chronic rheumatic condition who currently
      smoke are more likely to report averaging <6 h of sleep per night and frequent
      insomnia compared to individuals with a chronic rheumatic condition who never
      smoked. These results suggest both a unique and additive relationship between
      smoking and sleep in individuals with a chronic rheumatic condition. Findings can
      likely be generalized to other conditions commonly associated with chronic pain.

PMID- 22864599
TI  - Antibacterial activity of hypocrellin A against Staphylococcus aureus.
AB  - The antibacterial activity and acting mechanism of hypocrellin A (HA) were
      conducted regarding in vitro activity of HA on Staphylococcus aureus GZ86 by
      analyzing the growth, permeability, and morphology of the bacterial cells
      following treatment with HA. The experimental results indicated 1.5 mg/l HA could
      completely inhibit the growth of 107 CFU/ml S. aureus cells in liquid beef
      extract-peptone medium under a halogen-tungsten lamp for 120 min. Meanwhile, HA
      resulted in the leakage of reducing sugars and proteins and induced the
      respiratory chain dehydrogenases into inactive state, suggesting that HA were
      able to destroy the permeability of the bacterial membranes. When the cells of S.
      aureus were exposed to 2.5 mg/l HA under a halogen-tungsten lamp for 120 min,
      many pits and gaps were observed in bacterial cells by scanning electron
      microscopy, and the cell wall was fragmentary, indicating the bacterial cells
      were damaged severely. The experiments strongly confirmed the contribution of
      multiform reactive oxygen species (ROS) to bactericidal effect. In conclusion,
      the combined results suggested that ROS may damage the structure of bacterial
      cell wall and depress the activity of some membranous enzymes, which cause S.
      aureus bacteria to die eventually.

PMID- 22864600
TI  - Isolation of oxalic acid tolerating fungi and decipherization of its potential to
      control Sclerotinia sclerotiorum through oxalate oxidase like protein.
AB  - Oxalic acid plays major role in the pathogenesis by Sclerotinia sclerotiorum; it
      lowers the pH of nearby environment and creates the favorable condition for the
      infection. In this study we examined the degradation of oxalic acid through
      oxalate oxidase and biocontrol of Sclerotinia sclerotiorum. A survey was
      conducted to collect the rhizospheric soil samples from Indo-Gangetic Plains of
      India to isolate the efficient fungal strains able to tolerate oxalic acid. A
      total of 120 fungal strains were isolated from root adhering soils of different
      vegetable crops. Out of 120 strains a total of 80 isolates were able to grow at
      10 mM of oxalic acid whereas only 15 isolates were grow at 50 mM of oxalic acid
      concentration. Then we examined the antagonistic activity of the 15 isolates
      against Sclerotinia sclerotiorum. These strains potentially inhibit the growth of
      the test pathogen. A total of three potential strains and two standard cultures
      of fungi were tested for the oxalate oxidase activity. Strains S7 showed the
      maximum degradation of oxalic acid (23 %) after 60 min of incubation with fungal
      extract having oxalate oxidase activity. Microscopic observation and ITS
      (internally transcribed spacers) sequencing categorized the potential fungal
      strains into the Aspergillus, Fusarium and Trichoderma. Trichoderma sp. are well
      studied biocontrol agent and interestingly we also found the oxalate oxidase type
      activity in these strains which further strengthens the potentiality of these
      biocontrol agents.

PMID- 22864601
TI  - Detection and quantification of cultured marine Alexandrium species by real-time
      PCR.
AB  - The occurrence of harmful algal blooms (HABs) throughout the world has increased
      and poses a large threat to human health, fishery resources and tourism
      industries. The genus Alexandrium includes a number of toxic species associated
      with HABs. Therefore, it is very important to rapidly detect and monitor the
      harmful algae, such as Alexandrium genus. In this study, a standard curve of
      plasmid containing 18S rDNA-28S rDNA region from Alexandrium catenella was
      constructed and 5.8S rDNA sequence served as the primer of the real-time PCR.
      Cultured A. catenella, Alexandrium affine, Alexandrium lusitanicum and
      Alexandrium minutum samples were analyzed by real-time PCR using the same set of
      primers simultaneously. Using microscopy cells counts, 5.8S rDNA copies per cell
      and total DNA per cell were estimated. This assay method is promising for rapid
      detection of large number of Alexandrium samples.

PMID- 22864602
TI  - Optimization of fermentation process for the production of intracellular
      polysaccharide from Paecilomyces cicadae and the immuno-stimulating activity of
      intracellular polysaccharide.
AB  - Optimization of fermentation process for the production of intracellular
      polysaccharide (IPS) from the fungus Paecilomyces cicadae and the immuno
      stimulating activity of IPS were carried out. The quantitative effects of initial
      pH, fermentation temperature and time on the yield of IPS content produced by P.
      cicadae in submerged fermentation were investigated separately using response
      surface methodology (RSM). The three factors chosen for the present investigation
      were based on the results of a previous Plackett-Burman (PB) design. The
      experimental data obtained were fitted to a second-order polynomial equation
      using multiple regression analysis and also analyzed by appropriate statistical
      methods. RSM analysis showed good correspondence between experimental and
      predicted values. It was found that three parameters represented significant
      effect. Probability value (p < 0.0001) demonstrated a very high significance for
      the regression model. By solving the regression equation and analyzing the
      response surface contour plots, the optimal process parameters were determined,
      i.e. fermentation temperature 24.53  degrees C, initial pH 7.46 and fermentation
      time 73.9 h. The maximum predicted yield of IPS was 356.02 MUg/ml under the
      optimal conditions. Meanwhile, IPS from P. cicadae was found to have direct
      immuno-stimulating activity in vitro on murine macrophage RAW264.7 proliferative
      response and to stimulate nitric oxide generation in a dose-dependent manner.

PMID- 22864603
TI  - Alcohol intake revisited: risks and benefits.
AB  - The relationship between alcohol consumption and health outcomes has a long
      history and has generated much research. Heavy drinking is detrimental to health;
      however, there is considerable and convincing evidence from both short-term
      biochemical experimental studies and observational studies of a beneficial
      association with certain health outcomes related to atherosclerotic processes.
      This beneficial association is most important for an average alcohol intake of
      one to two drinks per day. Important factors in determining the magnitude or
      direction of effects have been identified. Most criticisms based on
      methodological issues have been dismissed in recent years from an epidemiological
      point of view. However, important questions remain about the circumstances of
      such a beneficial association. The net effect of alcohol consumption on health
      outcomes is detrimental overall, owing to the negative effect of cancers,
      infectious disease, gastrointestinal diseases, alcohol-use disorders and
      injuries.

PMID- 22864604
TI  - Susceptibility screening of hyphae-forming fungi with a new, easy, and fast
      inoculum preparation method.
AB  - In vitro susceptibility testing of clinically important fungi becomes more and
      more essential due to the rising number of fungal infections in patients with
      impaired immune system. Existing standardized microbroth dilution methods for in
      vitro testing of molds (CLSI, EUCAST) are not intended for routine testing. These
      methods are very time-consuming and dependent on sporulating of hyphomycetes. In
      this multicentre study, a new (independent of sporulation) inoculum preparation
      method (containing a mixture of vegetative cells, hyphae, and conidia) was
      evaluated. Minimal inhibitory concentrations (MIC) of amphotericin B,
      posaconazole, and voriconazole of 180 molds were determined with two different
      culture media (YST and RPMI 1640) according to the DIN (Deutsches Institut fur
      Normung) microdilution assay. 24 and 48 h MIC of quality control strains, tested
      per each test run, prepared with the new inoculum method were in the range of
      DIN. YST and RPMI 1640 media showed similar MIC distributions for all molds
      tested. MIC readings at 48 versus 24 h yield 1 log(2) higher MIC values and more
      than 90 % of the MICs read at 24 and 48 h were within +/- 2 log(2) dilution. MIC
      end point reading (log(2 MIC-RPMI 1640)-log(2 MIC-YST)) of both media
      demonstrated a tendency to slightly lower MICs with RPMI 1640 medium. This study
      reports the results of a new, time-saving, and easy-to-perform method for
      inoculum preparation for routine susceptibility testing that can be applied for
      all types of spore-/non-spore and hyphae-forming fungi.

PMID- 22864605
TI  - Transnodal lymphangiography in the diagnosis and treatment of genital lymphedema.
AB  - PURPOSE: To report the success of groin nodal lymphography in the diagnosis and
      treatment of genital lymphedema. METHODS AND MATERIALS: We present one female (8
      years old [patient no. 1]) and two male (69 and [patient no. 2] 31 years old
      [patient no. 3], respectively) patients with genital lymphedema in whom
      conservative treatment failed. The girl also had lymphorrhagia. Genital
      lymphedema was caused by radical cystectomy (patient no. 2), lymphatic
      hyperplasia (patient no. 1), and idiopathic lymphangitis (patient no. 3). All of
      them underwent ultrasound-guided bilateral groin lymph node puncture. Afterward,
      4-8 ml Lipiodol Ultra-Fluide (Guerbet) were injected at a rate of 0.2 ml/s.
      Lipiodol progression was assessed by fluoroscopy. Computed tomography scan of the
      abdomen and pelvis was performed immediately after and again at 24 h after the
      procedure to confirm the leak. The follow-up period was 15, 13, and 9 months,
      respectively. Technical success was considered as bilateral pelvic and abdominal
      filling of lymphatic vessels. Therapeutic success was considered as improvement
      or disappearance of genital lymphedema and/or lymphorrhagia. RESULTS: Lipiodol
      leak to the scrotum was observed in patients no. 2 and 3. Lymphaticopelvic
      fistula and genital lymphatic hyperplasia were seen in patient no. 1. Genital
      lymphedema diminished within 1 week and almost disappeared in two cases (patients
      no. 1 and 3) or significantly improved (patient no. 2). lymphorrhagia also
      resolved in patient no. 1. No recurrence or worsening was detected during follow
      up. CONCLUSION: Therapeutic lymphangiography by lymph node injection seems to be
      effective to treat genital lymphedema. Lymph node puncture lymphangiography is
      feasible and less cumbersome than pedal lymphangiography.

PMID- 22864606
TI  - Transjugular insertion of bare-metal biliary stent for the treatment of distal
      malignant obstructive jaundice complicated by coagulopathy.
AB  - PURPOSE: This study was designed to investigate retrospectively the feasibility
      of transjugular insertion of biliary stent (TIBS) for the treatment of distal
      malignant obstructive jaundice complicated by coagulopathy. METHODS: Between
      April 2005 and May 2010, six patients with distal malignant obstructive jaundice
      associated with coagulopathy that was unable to be corrected underwent TIBS at
      our institution for the palliation of jaundice. Patients' medical record and
      imaging results were reviewed to obtain information about demographics, procedure
      details, complications, and clinical outcomes. RESULTS: The intrahepatic biliary
      tract was successfully accessed in all six patients via transjugular approach.
      The procedure was technically successfully in five of six patients, with a bare
      metal stent implanted after traversing the biliary strictures. One procedure
      failed, because the guidewire could not traverse the biliary occlusion. One week
      after TIBS, the mean serum bilirubin in the five successful cases had decreased
      from 313 MUmol/L (range 203.4-369.3) to 146.2 MUmol/L (range 95.8-223.3) and had
      further decreased to 103.6 MUmol/L (range 29.5-240.9) at 1 month after the
      procedure. No bleeding, sepsis, or other major complications were observed after
      the procedure. The mean survival of these five patients was 4.5 months (range 1.9
      5.8). On imaging follow-up, there was no evidence of stent stenosis or migration,
      with 100 % primary patency. CONCLUSIONS: When the risks of hemorrhage from
      percutaneous transhepatic cholangiodrainage are high, TIBS may be an effective
      alternative for the treatment of distal malignant obstructive jaundice.

PMID- 22864607
TI  - Feasibility and safety of vascular closure devices in an antegrade approach to
      either the common femoral artery or the superficial femoral artery.
AB  - INTRODUCTION: The purpose of the present study was to analyze complications
      following antegrade puncture of the common femoral artery (CFA) and the
      superficial femoral artery (SFA) using vascular closure systems (VCS). METHODS: A
      single-center, retrospective study was performed after obtaining approval from
      the institutional review board and informed consent from all patients. At our
      center, the CFA or SFA are used for arterial access. All patients were evaluated
      clinically on the same day. If there was any suspicion of an access site problem,
      Duplex ultrasound was performed. RESULTS: Access location was the CFA in 50
      patients and the SFA in 130 patients. The sheath size ranged from 4F to 10F. Two
      patients had to be excluded because of lack of follow-up. Successful hemostasis
      was achieved in 162 of 178 cases (91 %). The following complications were
      observed in 16 patients (8.9 %): 4 pseudoaneurysms (2.2 %), 11 hematomas (6.2 %),
      and 1 vascular occlusion (0.5 %). The two pseudoaneurysms healed spontaneously,
      in one case an ultrasound-guided thrombin injection was performed, and one
      aneurysm was compressed manually. No further medical therapy was needed for the
      hematomas. The one vascular occlusion was treated immediately with angioplasty
      using a contralateral approach. No significant difference was noted between the
      CFA and the SFA group with respect to complications (p = 1.000). CONCLUSIONS: The
      use of closure devices for an antegrade approach up to 10F is feasible and safe.
      No differences in low complication rates were observed between CFA and SFA.

PMID- 22864608
TI  - Novel image cytometric method for detection of physiological and metabolic
      changes in Saccharomyces cerevisiae.
AB  - The studying and monitoring of physiological and metabolic changes in
      Saccharomyces cerevisiae (S. cerevisiae) has been a key research area for the
      brewing, baking, and biofuels industries, which rely on these economically
      important yeasts to produce their products. Specifically for breweries,
      physiological and metabolic parameters such as viability, vitality, glycogen,
      neutral lipid, and trehalose content can be measured to better understand the
      status of S. cerevisiae during fermentation. Traditionally, these physiological
      and metabolic changes can be qualitatively observed using fluorescence microscopy
      or flow cytometry for quantitative fluorescence analysis of fluorescently labeled
      cellular components associated with each parameter. However, both methods pose
      known challenges to the end-users. Specifically, conventional fluorescent
      microscopes lack automation and fluorescence analysis capabilities to
      quantitatively analyze large numbers of cells. Although flow cytometry is
      suitable for quantitative analysis of tens of thousands of fluorescently labeled
      cells, the instruments require a considerable amount of maintenance, highly
      trained technicians, and the system is relatively expensive to both purchase and
      maintain. In this work, we demonstrate the first use of Cellometer Vision for the
      kinetic detection and analysis of vitality, glycogen, neutral lipid, and
      trehalose content of S. cerevisiae. This method provides an important research
      tool for large and small breweries to study and monitor these physiological
      behaviors during production, which can improve fermentation conditions to produce
      consistent and higher-quality products.

PMID- 22864610
TI  - Social error monitoring in macaque frontal cortex.
AB  - Although much learning occurs through direct experience of errors, humans and
      other animals can learn from the errors of other individuals. The medial frontal
      cortex (MFC) processes self-generated errors, but the neuronal architecture and
      mechanisms underlying the monitoring of others' errors are poorly understood.
      Exploring such mechanisms is important, as they underlie observational learning
      and allow adaptive behavior in uncertain social environments. Using two paired
      monkeys that monitored each other's action for their own action selection, we
      identified a group of neurons in the MFC that exhibited a substantial activity
      increase that was associated with another's errors. Nearly half of these neurons
      showed activity changes consistent with general reward-omission signals, whereas
      the remaining neurons specifically responded to another's erroneous actions.
      These findings indicate that the MFC contains a dedicated circuit for monitoring
      others' mistakes during social interactions.

PMID- 22864611
TI  - HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2
      promoter activity.
AB  - Histone deacetylases (HDACs) compact chromatin structure and repress gene
      transcription. In schizophrenia, clinical studies demonstrate that HDAC
      inhibitors are efficacious when given in combination with atypical
      antipsychotics. However, the molecular mechanism that integrates a better
      response to antipsychotics with changes in chromatin structure remains unknown.
      Here we found that chronic atypical antipsychotics downregulated the
      transcription of metabotropic glutamate 2 receptor (mGlu2, also known as Grm2),
      an effect that was associated with decreased histone acetylation at its promoter
      in mouse and human frontal cortex. This epigenetic change occurred in concert
      with a serotonin 5-HT(2A) receptor-dependent upregulation and increased binding
      of HDAC2 to the mGlu2 promoter. Virally mediated overexpression of HDAC2 in
      frontal cortex decreased mGlu2 transcription and its electrophysiological
      properties, thereby increasing psychosis-like behavior. Conversely, HDAC
      inhibitors prevented the repressive histone modifications induced at the mGlu2
      promoter by atypical antipsychotics, and augmented their therapeutic-like
      effects. These observations support the view of HDAC2 as a promising new target
      for schizophrenia treatment.

PMID- 22864612
TI  - Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly.
AB  - Synapse formation and maturation requires bidirectional communication across the
      synaptic cleft. The trans-synaptic Neurexin-Neuroligin complex can bridge this
      cleft, and severe synapse assembly deficits are found in Drosophila melanogaster
      neuroligin (Nlg1, dnlg1) and neurexin (Nrx-1, dnrx) mutants. We show that the
      presynaptic active zone protein Syd-1 interacts with Nrx-1 to control synapse
      formation at the Drosophila neuromuscular junction. Mutants in Syd-1 (RhoGAP100F,
      dsyd-1), Nrx-1 and Nlg1 shared active zone cytomatrix defects, which were
      nonadditive. Syd-1 and Nrx-1 formed a complex in vivo, and Syd-1 was important
      for synaptic clustering and immobilization of Nrx-1. Consequently, postsynaptic
      clustering of Nlg1 was affected in Syd-1 mutants, and in vivo glutamate receptor
      incorporation was changed in Syd-1, Nrx-1 and Nlg1 mutants. Stabilization of
      nascent Syd-1-Liprin-alpha (DLiprin-alpha) clusters, important to initialize
      active zone formation, was Nlg1 dependent. Thus, cooperation between Syd-1 and
      Nrx-1-Nlg1 seems to orchestrate early assembly processes between pre- and
      postsynaptic membranes, promoting avidity of newly forming synaptic scaffolds.

PMID- 22864614
TI  - Unexpected difficult intubation owing to a tracheal web in a patient with past
      history of a Fontan procedure.

PMID- 22864613
TI  - Behavior-dependent specialization of identified hippocampal interneurons.
AB  - A large variety of GABAergic interneurons control information processing in the
      hippocampal circuits governing the formation of neuronal representations. Whether
      distinct hippocampal interneuron types contribute differentially to information
      processing during behavior is not known. We employed a new technique for
      recording and labeling interneurons and pyramidal cells in drug-free, freely
      moving rats. Recorded parvalbumin-expressing basket interneurons innervated
      somata and proximal pyramidal cell dendrites, whereas nitric oxide synthase- and
      neuropeptide Y-expressing ivy cells provided synaptic and extrasynaptic dendritic
      modulation. Basket and ivy cells showed distinct spike-timing dynamics, firing at
      different rates and times during theta and ripple oscillations. Basket, but not
      ivy, cells changed their firing rates during movement, sleep and quiet
      wakefulness, suggesting that basket cells coordinate cell assemblies in a
      behavioral state-contingent manner, whereas persistently firing ivy cells might
      control network excitability and homeostasis. Different interneuron types provide
      GABA to specific subcellular domains at defined times and rates, thereby
      differentially controlling network activity during behavior.

PMID- 22864615
TI  - The 2012 Frank Stinchfield Award: Decreasing patient activity with aging:
      implications for crosslinked polyethylene wear.
AB  - BACKGROUND: Patient activity influences polyethylene wear. However, it is unclear
      how individual activity changes with patient aging after THA. QUESTIONS/PURPOSES:
      We quantified changes in individual gait cycles and gait speed, assessed age
      related differences in these parameters, and determined their relationship to
      polyethylene wear. METHODS: A microprocessor was worn on the ankle to quantify
      the activity of 14 healthy patients with a well-functioning THA at two time
      periods: early (within 3.5 years of implantation) and late (10-13 postoperative
      years). Wear was measured on serial radiographs using edge detection-based
      software. RESULTS: Mean activity decreased by 16% from the early to the late
      period: 2.04 million gait cycles/year to 1.71 million gait cycles/year. Mean gait
      speed decreased by 9%: 15.4 cycles/minute to 14.0 cycles/minute. The activity of
      the 10 patients who were younger than 65 years at surgery decreased by 14% (2.34
      million gait cycles/year to 2.02 million gait cycles/year), while the four
      patients 65 years or older at surgery decreased by 28% (1.29 million gait
      cycles/year to 0.94 million gait cycles/year). Gait speed was 26% slower for
      patients 65 years or older than for patients younger than 65 years. The mean
      linear penetration rate decreased by 42% from the first 5 years (early wear rate)
      to the next 8 years (late wear rate, 5-13 years): 0.043 mm/year to 0.025 mm/year.
      CONCLUSIONS: The greatest patient activity and wear occurred during the first 5
      years. Walking speed and gait cycles both decreased with aging, resulting in
      deceasing wear over time.

PMID- 22864616
TI  - Corrosion at the cone/taper interface leads to failure of large-diameter metal-on
      metal total hip arthroplasties.
AB  - BACKGROUND: Metal-on-metal (MoM) THAs have reduced wear rates compared with metal
      on-polyethylene. However, elevated serum metal ion levels and pseudotumors have
      been reported in large MoM articulations. QUESTIONS/PURPOSES: We therefore
      determined (1) if corrosion occurred at the cone/taper interface leading to
      instability in patients with large-diameter THAs; (2) how patients presented
      clinically and radiographically; (3) if adverse periprosthetic tissue reactions
      occurred; (4) whether metal was released from the implants into the
      periprosthetic tissues; and (5) if head size correlated with metal release.
      METHODS: We reviewed 114 patients who had revisions of large-diameter head MoM
      articulations. Mean time of implantation was 46 months. To identify adverse
      reactions and particle load, tissues were stained by hematoxylin and eosin and
      CD3/CD20/CD68 antibodies. Periprosthetic tissues were analyzed for metal content
      and distribution in different regions. Electrochemical reactions between the stem
      and adapter were investigated by a minicell electrode. RESULTS: Electrochemical
      studies on the stem and the head adapter showed a risk for galvanic corrosion.
      Ninety-four percent of patients had instability at the cone/taper interface. All
      patients presented with early clinical symptoms; 59 patients had radiographic
      signs of loosening. One hundred four patients had foreign body reactions and
      necrosis. The largest amounts of metal released were titanium or iron. We found
      no correlation between head size and metal ion release. CONCLUSIONS: These
      findings suggest that in modular cone/taper connections, friction of the MoM
      articulations may cause failure of the cone/taper interface leading to galvanic
      corrosion and loosening. It is unclear whether the design of this MoM system
      provides sufficient stability at the taper.

PMID- 22864617
TI  - The ACL in the arthritic knee: how often is it present and can preoperative tests
      predict its presence?
AB  - BACKGROUND: TKA with retention of the anterior cruciate ligament (ACL) may
      improve kinematics and function. However, conflicting reports exist concerning
      the prevalence of intact ACLs at the time of TKA. QUESTIONS/PURPOSES: Therefore,
      we asked: (1) what was the ACL status at TKA; (2) what was the sensitivity and
      specificity of the Lachman test; (3) did MRI ACL integrity correlate with
      intraoperative observation; (4) did MRI tibial wear patterns correlate with ACL
      integrity; and (5) did ACL status depend on age or sex? METHODS: We evaluated 200
      patients for ACL integrity at the time of TKA. All patients underwent a Lachman
      test under anesthesia. Intraoperatively, the ACL was characterized as intact,
      frayed, disrupted, or absent. In 100 patients, MRIs were performed, from which
      the ACL was graded as intact, indeterminate, or disrupted, and the AP location of
      tibial wear was categorized. RESULTS: The ACL was intact in 155 patients (78%).
      The Lachman test alone had poor diagnostic ability. The MRI predicted a tear, but
      we observed two ACLs with indeterminate status that were disrupted. All knees
      with anterior wear on the medial tibial condyle had an intact ACL (n = 45), and
      all knees with posterior wear on the medial tibial condyle had a disrupted ACL (n
      = 8). CONCLUSIONS: Although the Lachman test alone had poor sensitivity, when
      combined with MRI they together provide a sensitivity of 93.3% and specificity of
      99%, which we believe makes these reasonable tests for assessing ACL status in
      the arthritic knee.

PMID- 22864618
TI  - Preliminary pain and function after labral reconstruction during femoroacetabular
      impingement surgery.
AB  - BACKGROUND: Labral refixation rather than resection provides better pain relief
      and function after femoroacetabular impingement (FAI) surgery. When the labrum is
      absent, degenerated, or is irreparable, reconstruction may provide a favorable
      biomechanical environment for the hip. However, it is unclear whether labral
      reconstruction relieves pain and restores function. QUESTION/PURPOSES: In
      patients undergoing FAI surgery with concomitant labral reconstruction, (1) Do
      they note subjective improvement in pain at latest followup? (2) What is their
      postoperative activity level? (3) What are the complications, reoperation rates,
      and reasons for failure? METHODS: We retrospectively reviewed all 19 patients who
      underwent labral reconstruction in 20 hips at the time of surgical hip
      dislocation between August 2007 and February 2011. We assessed improvement in
      pain and function, complications, and subsequent surgery through a chart review
      and questionnaire. The minimum followup was 12 months (average, 26.4 months;
      range, 12-56 months). RESULTS: Three hips in three patients were converted to THA
      within 36 months of their surgical hip dislocation for continued preoperative
      pain. Of the 17 hips not undergoing THA, 15 reported subjective improvement in
      preoperative pain and function. The average UCLA score was 8.5 (range, 5-10). We
      observed no complications associated with the labral reconstruction itself.
      CONCLUSION: The majority of patients with reconstructed acetabular labra reported
      improvement in their hip pain and function after surgery. The causes of
      persistent symptoms and conversion to THA remain uncertain. The data and
      conclusions of this study are limited secondary to lack of objective outcome
      measures. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22864619
TI  - Determinants of direct medical costs in primary and revision total knee
      arthroplasty.
AB  - BACKGROUND: TKA procedures are increasing rapidly, with substantial cost
      implications. Determining cost drivers in TKA is essential for care improvement
      and informing future payment models. QUESTIONS/PURPOSES: We determined the
      components of hospitalization and 90-day costs in primary and revision TKA and
      the role of demographics, operative indications, comorbidities, and complications
      as potential determinants of costs. METHODS: We studied 6475 primary and 1654
      revision TKA procedures performed between January 1, 2000, and September 31,
      2008, at a single center. Direct medical costs were measured by using
      standardized, inflation-adjusted costs for services and procedures billed during
      the 90-day period. We used linear regression models to determine the cost impact
      associated with individual patient characteristics. RESULTS: The largest
      proportion of costs in both primary and revision TKA, respectively, were for room
      and board (28% and 23%), operating room (22% and 17%), and prostheses (13% and
      24%). Prosthesis costs were almost threefold higher in revision TKA than in
      primary TKA. Revision TKA procedures for infections and bone and/or prosthesis
      fractures were approximately 25% more costly than revisions for instability and
      loosening. Several common comorbidities were associated with higher costs.
      Patients with vascular and infectious complications had longer hospital stays and
      at least 80% higher 90-day costs as compared to patients without complications.
      CONCLUSIONS: High prosthesis costs in revision TKA represent a factor potentially
      amenable to cost containment efforts. Increased costs associated with demographic
      factors and comorbidities may put providers at financial risk and may jeopardize
      healthcare access for those patients in greatest need.

PMID- 22864620
TI  - Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: results of a
      prospective randomised study.
AB  - INTRODUCTION: Conventional haemorrhoidectomy (CH) is well known to cause
      significant post-operative pain and delayed return to daily activities. Both
      surgical wounds and sphincterial apparatus spasms are likely responsible for the
      pain. In this study, we evaluated the role of glyceryl trinitrate ointment (GTN)
      in reducing post-operative pain, ameliorating wound healing and recovery after
      CH. PATIENTS AND METHODS: Between 01/08 and 12/11, 203 patients with symptomatic
      haemorrhoids were enrolled in the study and received (103 patients) or not (100
      patients) 0.4 % GTN ointment for 6 weeks after surgery. Pain was assessed using a
      10-cm linear visual analogue scale (VAS). Data on post-operative pain, wound
      secretion and bleeding, return to normal activities and complications were
      recorded. Data were analysed using Fisher's exact and Mann-Whitney tests.
      RESULTS: GTN-treated group experienced significantly less pain during the first
      week after surgery (p < 0.0001). This difference was more evident starting from
      post-operative day 4 (p < 0.0001). A significant higher percentage of untreated
      patients experienced severe pain (mean VAS score > 7) (10 % vs 31 %). There were
      significant differences in terms of secretion time (p = 0.0052) and bleeding time
      (p = 0.02) in favor of GTN. In addition, the duration of itching was less in the
      GTN group (p = 0.0145). Patients treated with GTN were able to an early return to
      daily activities compared to untreated (p < 0.0001). Fifteen GTN-treated patients
      (14.6 %) discontinued the application because of local discomfort and headache.
      CONCLUSIONS: GTN ointment enhances significantly post-operative recovery,
      reducing pain in terms of duration and intensity. This effect might be secondary
      to a faster wound healing expressed by reduced secretion, bleeding and itching
      time.

PMID- 22864621
TI  - The role of colonic mast cells and myenteric plexitis in patients with
      diverticular disease.
AB  - BACKGROUND: Gut mast cells represent an important cell population involved in
      intestinal homeostasis and inflammatory processes. However, their possible role
      has not to date been investigated in colonic diverticular disease. AIMS: This
      study aims to evaluate colonic mast cells in patients undergoing surgery for
      diverticular disease. METHODS: Surgical resection samples from 27 patients
      undergoing surgery for diverticular disease (12 emergency procedures for severe
      disease and 15 elective procedures) were evaluated. The number of mast cells was
      assessed in the various layers by means of a specific antibody (tryptase) and
      compared with those evaluated in ten controls. In patients with mast cells
      degranulation, double immunohistochemistry, also assessing nerve fibres, was
      carried out. In addition, the presence of myenteric plexitis was sought. RESULTS:
      Compared with controls, the number of mast cells in diverticular patients was
      significantly increased, both as an overall figure and in the various layers of
      the large bowel. In patients in whom mast cells degranulation was present, these
      were always closed to nerve fibres. No differences were found between the two
      subgroups of patients with respect to the number and distribution of mast cells;
      however, all patients undergoing emergency surgery (but none of those undergoing
      elective procedures) had myenteric plexitis, represented by lymphocytic
      infiltration in 67 % and eosinophilic infiltration in 33 % of cases. CONCLUSIONS:
      Patients with diverticular disease display an increase of mast cells in the large
      bowel. The presence of myenteric plexitis in those with complicated, severe
      disease, suggest that this could represent a histopathologic marker of more
      aggressive disease.

PMID- 22864623
TI  - Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA
      nephropathy and breast adenocarcinoma.
AB  - Glycosylation abnormalities have been observed in autoimmune diseases and cancer.
      Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn
      and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune
      disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although
      different for MUC1 and IgA1, include dysregulation in glycosyltransferase
      expression, stability, and/or intracellular localization. Moreover, these
      aberrant glycoproteins are recognized by antibodies, although with different
      consequences. In breast cancer, elevated levels of antibodies recognizing
      aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the
      antibodies recognizing aberrant IgA1 are part of the pathogenetic process.

PMID- 22864625
TI  - Density functional study on the adsorption of the drug isoniazid onto pristine
      and B-doped single wall carbon nanotubes.
AB  - The current study explores a new strategy to incorporate single wall carbon
      nanotubes (SWNTs)/doped SWNTs as carrier modules in target-specific
      administration of antitubercular chemotherapeutics through covalent and
      noncovalent functionalization onto the nanotube sidewall. Density functional
      studies illustrate that noncovalent functionalization of isoniazid (INH) is
      preferred over covalent attachment, exhibiting low adsorption energy values, HOMO
      LUMO gap and comparison of quantum molecular descriptors performed in (5,5) and
      (9,0) SWNT systems. Substitution doping of boron facilitates the adsorption of
      INH onto the otherwise inert nanotube. Frontier orbital analysis reveals
      reorientation of electronic charge in the nanotubes after functionalization, the
      effect being more pronounced in the case of doped nanotubes. The charge transfer
      is significant in covalent functionalization of INH via the B-dopant atom,
      whereas in noncovalent functionalization a small amount of charge transfer is
      noted. Solvation studies demonstrate the dissolution of INH in B-doped (5,5) and
      (9,0) SWNTs to be higher compared to pristine nanotube-INH complexes.
      Functionalization of nanotubes via covalent and noncovalent means can foster
      pioneering prospects especially for experimental studies in this area of
      research.

PMID- 22864624
TI  - The implications of viral reservoirs on the elite control of HIV-1 infection.
AB  - The mechanisms by which a small percentage of HIV-1 infected individuals known as
      elite suppressors or controllers are able to control viral replication are not
      fully understood. Early cases of viremic control were attributed to infection
      with defective virus, but subsequent work has demonstrated that infection with a
      defective virus is not the exclusive cause of control. Replication-competent
      virus has been isolated from patients who control viral replication, and studies
      have demonstrated that evolution occurs in plasma virus but not in virus isolates
      from the latent reservoir. Additionally, transmission pair studies have
      demonstrated that patients infected with similar viruses can have dramatically
      different outcomes of infection. An increased understanding of the viral factors
      associated with control is important to understand the interplay between viral
      replication and host control, and has implications for the design of an effective
      therapeutic vaccine that can lead to a functional cure of HIV-1 infection.

PMID- 22864622
TI  - Aurora A kinase (AURKA) in normal and pathological cell division.
AB  - Temporally and spatially controlled activation of the Aurora A kinase (AURKA)
      regulates centrosome maturation, entry into mitosis, formation and function of
      the bipolar spindle, and cytokinesis. Genetic amplification and mRNA and protein
      overexpression of Aurora A are common in many types of solid tumor, and
      associated with aneuploidy, supernumerary centrosomes, defective mitotic
      spindles, and resistance to apoptosis. These properties have led Aurora A to be
      considered a high-value target for development of cancer therapeutics, with
      multiple agents currently in early-phase clinical trials. More recently,
      identification of additional, non-mitotic functions and means of activation of
      Aurora A during interphase neurite elongation and ciliary resorption have
      significantly expanded our understanding of its function, and may offer insights
      into the clinical performance of Aurora A inhibitors. Here we review the mitotic
      and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context
      of protein structural information, and evaluate progress in understanding and
      inhibiting Aurora A in cancer.

PMID- 22864626
TI  - A plausible explanation for enhanced bioavailability of P-gp substrates in
      presence of piperine: simulation for next generation of P-gp inhibitors.
AB  - P-glycoprotein (P-gp) has a major role to play in drug pharmacokinetics and
      pharmacodynamics, since it effluxes many cytotoxic hydrophobic anticancer drugs
      from gastrointestinal tract, brain, liver and kidney. Piperine is known to
      enhance the bioavailability of curcumin, as a substrate of P-gp by at least
      2000%. Besides these at least 50 other substrates and inhibitors of P-gp have
      been reported so far. All P-gp inhibitors have diverse structures. Although
      little is known about binding of some flavonoids and steroids at the NBD
      (nucleotide binding domain) of P-gp in the vicinity of ATP binding site
      inhibiting its hydrolysis, a valid explanation of how P-gp accommodates such a
      diverse set of inhibitors is still awaited. In the present study, piperine up to
      100 MUM has not shown observable cytotoxic effect on MDCK cell line, and it has
      been shown to accumulate rhodamine by fluorescence microscopy and fluorescent
      activated cell sorter in MDCK cells. Computational simulation for piperine and
      some first and second generation P-gp inhibitors has shown that these dock at the
      NBD site of P-gp. A comparative simulation study has been carried out regarding
      their docking and binding energies. Binding conformation of P-gp co-crystallized
      complexes with ADP, AMP-PNP (Adenylyl-imidodiphosphate), and ATP were compared
      with piperine. The receptor based E-pharmacophore of docked piperine has been
      simulated to find common features amongst P-gp inhibitors. Finally it has been
      concluded that piperine could be utilized as base molecule for design and
      development of safe non-toxic inhibitor of P-gp in order to enhance the
      bioavailability of most of its substrates.

PMID- 22864627
TI  - Density functional investigation of CO adsorption on Ni-doped single-walled
      armchair (5,5) boron nitride nanotubes.
AB  - The adsorption of CO onto Ni-doped boron nitride nanotubes (BNNTs) was
      investigated using density functional theory at the B3LYP/LanL2DZ level of
      theory. The structures of the Ni-doped BNNTs and their CO-adsorbed configurations
      were obtained. It was found that the strength of adsorption of CO onto Ni-doped
      perfect BNNTs is higher than that on defective BNNTs. The electronic properties
      of all of the adsorption configurations of CO on Ni-doped BNNTs are reported.

PMID- 22864628
TI  - Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children
      with T-B-NK+ immunodeficiency.
AB  - Two infants are described who presented with 22q11.2 deletion and a T(-)B(-)NK(+)
      immune phenotype. For both infants, the initial diagnosis was athymia secondary
      to complete DiGeorge anomaly. The first infant underwent thymus transplantation
      but 6 months after transplantation had circulating thymus donor T cells; the
      patient did not develop recipient naive T cells. Genetic analyses revealed that
      both patients had Artemis deficiency, a rare form of severe combined
      immunodeficiency (SCID). Both infants have subsequently undergone bone marrow
      transplantation. These cases illustrate the importance and paradox of
      differentiating SCID from complete DiGeorge anomaly because hematopoietic stem
      cell transplantation (HSCT) is the preferred treatment for SCID but is
      ineffective for complete DiGeorge anomaly. However, if the thymus is completely
      absent, donor stem cells from a HSCT would not be able to be educated.

PMID- 22864629
TI  - Th2 responses in OVA-sensitized BALB/c mice are down-modulated by Mycobacterium
      bovis BCG treatment.
AB  - OBJECTIVE: This study aimed to determine whether Mycobacterium bovis Bacillus
      Calmette-Guerin (BCG) treatment can reverse an established allergic airway
      inflammation in a BALB/c mouse model of ovalbumin (OVA)-induced airway
      inflammation. METHODS: OVA sensitized BALB/c mice were challenged with
      aerosolized OVA on days 28 to 30, 34, 41 and 63. Mice were intranasal treated
      with BCG on days 35 and 42. Twenty-four hours after the last challenge, blood
      samples were collected to detect anti-OVA immunoglobulin isotypes, and
      bronchoalveolar lavage (BAL) was harvested for cell count. Additionally, lungs
      were collected for histological analysis, detection of the eosinophil peroxidase
      (EPO) activity and measurement of cytokines and CCL11. The expression of CTLA-4,
      Foxp3 and IL-10 was also determined in lung tissue by flow cytometry. RESULTS:
      BCG treatment was able to inhibit an established allergic Th2-response, by
      decreasing the allergen-induced eosinophilic inflammation, EPO activity, levels
      of CCL11 and IL-4, serum levels of IgE and IgG1. Mycobacteria treatment increased
      lung levels of IFN-gamma, IL-10 and TGF-beta, and expressions of Foxp3 and CTLA-4
      in CD4(+)T cells. Additionally, an increased production of IL-10 by CD8(+) T
      cells was observed, even though no detectable changes in CD4(+)IL-10(+) was
      noticed. CONCLUSION: BCG treatment inhibits features of allergic airway
      inflammation and the results suggest that the mechanism underlying the down
      regulatory effects of BCG on OVA-induced airway inflammation appear to be
      associated with the induction of both Th1 and T regulatory immune responses.

PMID- 22864631
TI  - Hydrogenolysis of beta-O-4 lignin model dimers by a ruthenium-xantphos catalyst.
AB  - Hydrogenolysis reactions of so-called lignin model dimers using a Ru-xantphos
      catalyst are presented (xantphos = 4,5-bis(diphenylphosphino)-9,9
      dimethylxanthene). For example, of some nine models studied, the alcohol, 2-(2
      methoxyphenoxy)-1-phenylethanol (1), with 5 mol% Ru(H)(2)(CO)(PPh(3))(xantphos)
      (18) in toluene-d(8) at 135  degrees C for 20 h under N(2), gives in ~95% yield
      the C-O cleavage hydrogenolysis products, acetophenone (14) and guaiacol (17),
      and a small amount (<5%) of the ketone, 2-(2-methoxyphenoxy)-1-phenylethanone
      (4), as observed by (1)H NMR spectroscopy. The in situ
      Ru(H)(2)(CO)(PPh(3))(3)/xantphos system gives similar findings, confirming a
      recent report (J. M. Nichols et al., J. Am. Chem. Soc., 2010, 132, 12554). The
      active catalyst is formulated 'for convenience' as 'Ru(CO)(xantphos)'. The
      hydrogenolysis mechanism proceeds by initial dehydrogenation to give the ketone
      4, which then undergoes hydrogenolysis of the C-O bond to give 14 and 17.
      Hydrogenolysis of 4 to 14 and 17 also occurs using the Ru catalyst under 1 atm
      H(2); in contrast, use of 3-hydroxy-2-(2-methoxyphenoxy)-1-phenyl-1-propanone
      (7), for example, where the CH(2) of 4 has been changed to CHCH(2)OH, gives a low
      yield (<=15%) of hydrogenolysis products. Similarly, the diol substrate, 2-(2
      methoxyphenoxy)-1-phenyl-1,3-propanediol (9), gives low yields of hydrogenolysis
      products. These low yields are due to formation of the catalytically inactive
      complexes Ru(CO)(xantphos)[C(O)C(OC(6)H(4)OMe)=C(Ph)O] (20) and/or
      Ru(CO)(xantphos)[C(O)CH=C(Ph)O] (21), where the organic fragments result from
      dehydrogenation of CH(2)OH moieties in 7 and 9. Trace amounts of
      Ru(CO)(xantphos)(OC(6)H(4)O), a catecholate complex, are isolated from the
      reaction of 18 with 1. Improved syntheses of 18 and lignin models are also
      presented.

PMID- 22864630
TI  - Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown
      Vialetto-Van Laere syndrome.
AB  - Brown-Vialetto-Van Laere syndrome (BVVLS [MIM 211530]) is a rare neurological
      disorder characterized by infancy onset sensorineural deafness and ponto-bulbar
      palsy. Mutations in SLC52A3 (formerly C20orf54), coding for riboflavin
      transporter 2 (hRFT2), have been identified as the molecular genetic correlate in
      several individuals with BVVLS. Exome sequencing of just one single case revealed
      that compound heterozygosity for two pathogenic mutations in the SLC52A2 gene
      coding for riboflavin transporter 3 (hRFT3), another member of the riboflavin
      transporter family, is also associated with BVVLS. Overexpression studies
      confirmed that the gene products of both mutant alleles have reduced riboflavin
      transport activities. While mutations in SLC52A3 cause decreased plasma
      riboflavin levels, concordant with a role of SLC52A3 in riboflavin uptake from
      food, the SLC52A2-mutant individual had normal plasma riboflavin concentrations,
      a finding in line with a postulated function of SLC52A2 in riboflavin uptake from
      blood into target cells. Our results contribute to the understanding of human
      riboflavin metabolism and underscore its role in the pathogenesis of BVVLS,
      thereby providing a rational basis for a high-dose riboflavin treatment.

PMID- 22864632
TI  - Chemical and bioassay analysis of estrogen pollution in the surface water of the
      Tiaoxi River, the source river for Taihu Lake.
AB  - The estrogen pollution in the Tiaoxi River, which is the main source river for
      Taihu Lake, was investigated by chemical and bioassay analysis. Most estrogens
      species, except estrone, were not detected by the chemical analysis using liquid
      chromatography coupled with tandem mass spectrometry. The concentration of
      estrone in the samples ranged from ND (below the detection limit) to 17.25 ng/L.
      The estrogen activity in most water samples was also determined by the yeast
      estrogen screen. The 17beta-estradiol equivalent in the intake of Taihu Lake was
      17.60 ng/L and was present in all water samples. This study demonstrates that
      combining chemical and bioassay analysis is an effective way to detect
      environmental contamination by estrogen species. Furthermore, the results
      indicate that the risk of estrogen contamination in the Tiaoxi River should not
      be ignored.

PMID- 22864633
TI  - Effect of bauxite mineralized soil on residual metal levels in some post harvest
      food crops in Jamaica.
AB  - The concentrations of nine residual metals in some Jamaican foods were determined
      using inductively coupled plasma mass spectrometry technique. Cadmium
      concentration was highest in yellow yam (0.21 mg/kg). Sweet potato had the
      highest concentrations of lead (0.31 mg/kg), arsenic (0.70 mg/kg) and mercury
      (0.35 mg/kg). Samples from Grove Place exceeded the regulatory limits of 0.1
      mg/kg for cadmium, lead and arsenic and 0.05 mg/kg for mercury. Significant
      correlations were found between soil and agricultural produce concentrations for
      cadmium and lead (r(2) >= 0.5). These results suggest that the elements were
      available in soluble forms in the soil for absorption by food crops.

PMID- 22864634
TI  - Organochlorine pesticide residues in bovine milk from organic farms in Chiapas,
      Mexico.
AB  - Thirty six samples of bovine milk were collected from Chiapas State, Mexico
      between January 2011 and December 2011 with the intention of identifying and
      quantifying organochlorine pesticide residues in organic farms. The analyses were
      done using gas chromatography with an electron capture detector (Ni(63)). In
      general the values found in raw milk were lower than the permissible limit
      proposed by FAO/WHO/Codex Alimentarius 2006. Average concentrations for alpha +
      beta HCH were 3.62 ng/g, gamma HCH 0.34 ng/g, heptachlor + epoxide 0.67 ng/g, DDT
      and isomers 1.53 ng/g, aldrin + dieldrin 0.77 ng/g, and endrin 0.66 ng/g (only
      present in samples from farm 2). The organic milk from Chiapas has shown low
      concentrations of pesticide residues in recent years and satisfies international
      and national regulations for commercialization.

PMID- 22864635
TI  - Fast genomic biomarker responses of retene and pyrene in liver of juvenile
      rainbow trout, Oncorhynchus mykiss.
AB  - We studied the transcriptive effects of two PAHs, retene (RET) and pyrene (PYR),
      in three equimolar sublethal concentrations (0.9-10 MUg/L) in the liver of
      juvenile rainbow trout, Oncorhynchus mykiss. After 24 h of in vivo exposure,
      expressions of selected genes (CYP1A, Hsp30, Hsp70, Grp78, Sep15, GP1) were
      analyzed by quantitative reverse transcription polymerase chain reaction (qRT
      PCR). These PAHs changed the studied gene transcriptions differently, but not
      significantly, except for CYP1A, which was induced only by RET. RET induced CYP1A
      gene expression even at low, environmentally realistic concentrations in the
      liver of juvenile rainbow trout.

PMID- 22864637
TI  - Multiple electrokinetic actuators for feedback control of colloidal crystal size.
AB  - We report a feedback control method to precisely target the number of colloidal
      particles in quasi-2D ensembles and their subsequent assembly into crystals in a
      quadrupole electrode. Our approach relies on tracking the number of particles
      within a quadrupole electrode, which is used in a real-time feedback control
      algorithm to dynamically actuate competing electrokinetic transport mechanisms.
      Particles are removed from the quadrupole using DC-field mediated electrophoretic
      electroosmotic transport, while high-frequency AC-field mediated
      dielectrophoretic transport is used to concentrate and assemble colloidal
      crystals. Our results show successful control of the size of crystals containing
      20 to 250 colloidal particles with less than 10% error. Assembled crystals are
      characterized by their radius of gyration, crystallinity, and number of edge
      particles, and demonstrate the expected size-dependent properties. Our findings
      demonstrate successful ensemble feedback control of the assembly of different
      sized colloidal crystals using multiple actuators, which has broad implications
      for control over nano- and micro- scale assembly processes involving colloidal
      components.

PMID- 22864638
TI  - No evidence for breast cancer susceptibility associated with variants of BRD7, a
      component of p53 and BRCA1 pathways.
AB  - BRD7 (bromodomain 7), a subunit of poly-bromo-associated BRG1-associated factor
      (PBAF)-specific Swi/Snf chromatin remodeling complexes, has been proposed as a
      tumour suppressor protein following its identification as an important component
      of both functional p53 and BRCA1 (breast cancer 1, early onset) pathways. As low
      BRD7 expression levels have been linked to p53-wild-type breast tumour cells, we
      hypothesized an implication of BRD7 germline alterations in the pathogenesis of
      hereditary breast cancer similar to that of TP53 in Li-Fraumeni syndrome. We
      performed sequence analysis of the BRD7 gene on 61 high-risk individuals with
      hereditary or very-early-onset breast cancer and 100 healthy controls. Four
      potentially disease-causing single-nucleotide alterations were detected within
      the cohort of breast cancer patients (one listed as a rare single-nucleotide
      polymorphism (SNP) in the NCBI (National Center for Biotechnology Information)
      SNP database). Two of the detected variants were also each found once within the
      control collective. Segregation analysis on both families of those carrying the
      remaining two variants revealed segregation of these BRD7 alterations independent
      of breast cancer. In conclusion, it seems that the BRD7 variants we detected
      represent rare polymorphisms and mainly rule out BRD7 as a frequent high
      penetrance breast cancer susceptibility gene. However, further analyses in larger
      cohorts of women with hereditary breast cancer should clarify the role of BRD7 in
      breast cancer predisposition.

PMID- 22864639
TI  - Non-synonymous polymorphism (Gln261Arg) of 12-lipoxygenase in colorectal and
      thyroid cancers.
AB  - 12-lipoxygenase (12-LOX) pathway which produces 12-HETE and hepoxiline HXA3 and
      HXB3, and induces production of reactive oxygen species and inflammation is
      increasingly being implicated in variety of cancers, including those of
      colorectal and thyroid cancers. Hence, we examined whether the functional
      polymorphism of 12-LOX (mRNA A835G; Protein Gln261Arg) has any association with
      human colorectal and thyroid cancers. In this communication, we report that the
      mutation is linked to colorectal cancer and thyroid cancers. Further, we also
      observed that the heterozygous mutant (AG) is more prevalent in females than in
      males. Frequencies of AA, AG and GG, respectively were 62.5, 36.2 and 1.3 % in
      controls, 36.5, 61.5 and 2.0 % in colorectal cancer cases and 35.6, 62.4 and 2.0
      % in thyroid cancer cases. The results obtained suggested a significant
      association of the heterogenous variant (AG) with the cancers. Relative risk of
      the cancers with the presence of the AG variant was found to be 2.9 and 4.0 for
      colorectal and thyroid cancers, respectively. However, the association of the
      variant (AG) was significant only in male colorectal cancer patients but not in
      female patients. On the other hand, prevalence of the AG variant is significantly
      higher in control females than in male control subjects. To the best of our
      knowledge, this is the first study that links the 12-LOX gene polymorphism with
      thyroid cancer and reveals a gender bias in the prevalence of the polymorphic
      variants in controls and colorectal cancer patients.

PMID- 22864640
TI  - High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast
      cancer.
AB  - Possession of a BRCA1/2 mutation increases risk of contralateral breast and
      ovarian cancer recurrence and may have an impact on health management decisions,
      such as imaging screening, preventive surgical interventions and systemic
      therapies. A hospital-based study was conducted to assess the frequency and
      spectrum of pathogenic germline BRCA1 and BRCA2 mutations in Polish women with
      familial and nonfamilial breast cancer. Genomic DNA was extracted from 1581 women
      with breast cancer and from 2225 healthy individuals. For genotyping BRCA1
      (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 3896delT, 4153delA,
      4184del4, 4160delAG, G5332A) mutations and BRCA2 (G1408T, 5467insT, 6174delT,
      6192delAT, 6675delTA, 8138del5, 9152delT, C9610T, 9630delC) mutations, a Custom
      TaqMan (Applied Biosystems) PCR-based technology was adopted. A BRCA1 mutation
      was found in 26 and 12.5 % of women with familial breast cancer and in 13 and 8.3
      % nonfamilial (sporadic) breast cancer, diagnosed before or after 50 years of
      age, respectively. A much lower frequency of BRCA2 mutation was observed. The
      predominance of seven BRCA1 mutations (5382insC, T300G, 3819del5, 185delAG,
      C5370T, 3875del4, 4153delA) studied in the Masovian voivodeship population
      confirmed a strong founder effect for BRCA1 mutations in the Polish population,
      and the results of BRCA2 testing confirmed a high diversity in the studied
      pathogenic mutations in BRCA2 gene. We propose offering inexpensive testing for
      the presence of BRCA1 founder mutations to all Polish women at the time of
      initial breast cancer diagnosis, regardless of the patient's family history or
      age of disease onset.

PMID- 22864642
TI  - In-vivo human brain molecular imaging with a brain-dedicated PET/MRI system.
AB  - Advances in the new-generation of ultra-high-resolution, brain-dedicated positron
      emission tomography-magnetic resonance imaging (PET/MRI) systems have begun to
      provide many interesting insights into the molecular dynamics of the brain.
      First, the finely delineated structural information from ultra-high-field MRI can
      help us to identify accurate landmark structures, thereby making it easier to
      locate PET activation sites that are anatomically well-correlated with metabolic
      or ligand-specific organs in the neural structures in the brain. This synergistic
      potential of PET/MRI imaging is discussed in terms of neuroscience and
      neurological research from both translational and basic research perspectives.
      Experimental results from the hippocampus, thalamus, and brainstem obtained with
      (18)F-fluorodeoxyglucose and (11)C-3-amino-4-(2
      dimethylaminomethylphenylsulfanyl)benzonitrile are used to demonstrate the
      potential of this new brain PET/MRI system.

PMID- 22864643
TI  - Inhibitory effect of IVIG on IL-17 production by Th17 cells is independent of
      anti-IL-17 antibodies in the immunoglobulin preparations.
AB  - PURPOSE: Th17 cells and their cytokines play a critical role in the pathogenesis
      of various autoimmune and inflammatory diseases. Recently, we have demonstrated
      that intravenous immunoglobulin (IVIG) suppresses differentiation, amplification,
      and functions of human Th17 cells. In this report we investigated whether IVIG
      inhibits IL-17 production by Th17 cells cultured in the presence of IL-23 and
      whether the inhibitory effect of IVIG on IL-17 production implicates anti-IL-17
      antibodies. METHODS: Naive CD4(+) T cells were stimulated in the presence of TGF
      beta, IL-21, and IL-23 for the differentiation of Th17 cells. Memory CD4(+) T
      cells were stimulated with IL-1beta, IL-6, and IL-23 for the amplification of
      Th17 cells. IVIG (0.15 mM) was added to the cells 12 h after initiation of
      cultures. IL-17A cytokine and anti-IL-17 antibodies were measured by ELISA.
      RESULTS: IL-23 did not deter the inhibitory effect of IVIG on IL-17 production
      from the differentiating and expanding Th17 cells. Further, suppression of IL-17
      by IVIG did not implicate anti-IL-17 antibodies in the immunoglobulin
      preparations. CONCLUSION: The effect of IVIG on the inhibition of IL-17
      production by Th17 cells is a consequence of modulation of Th17 cells and their
      intracellular signaling pathways and not due to passive neutralization of IL-17
      by anti-IL-17 antibodies in the immunoglobulin preparations.

PMID- 22864644
TI  - Predictive factors of downstaging of hepatocellular carcinoma beyond the Milan
      criteria treated with intra-arterial therapies.
AB  - PURPOSE: This study was designed to analyze the clinical results in patients
      suitable for liver transplantation with hepatocellular carcinoma (HCC) who
      exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to
      determine predictive factors of successful downstaging. METHODS: A total of 277
      consecutive patients with cirrhosis and HCC were treated by IAT (transarterial
      oily chemoembolization, transarterial chemoembolization, transarterial
      embolization) in a single center. Eighty patients exceed the Milan criteria.
      Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were
      excluded, with a final study population of 48 patients. Tumor response to IAT was
      evaluated with CT and/or MRI according to modified RECIST criteria. Successful
      downstaging was defined as a reduction in the number and size of viable tumors to
      within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at
      least 6 months. RESULTS: Nineteen patients (39 %) had their tumors successfully
      downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP
      level <100 ng/mL and 3-year calculated survival probability using the Metroticket
      calculator were the only independent predictors of successful downstaging (p <
      0.023 and p < 0.049 respectively). CONCLUSIONS: Biological characteristics of HCC
      as AFP levels <100 ng/mL and high 3-year calculated survival probability may
      predict a good response to downstage after IAT.

PMID- 22864645
TI  - Outcome measurements after oral cancer treatment: speech and speech-related
      aspects--an overview.
AB  - INTRODUCTION: Oral cancer and its surgical treatment impair speech quality by an
      alteration of the vocal tract. Local size and stage of the tumour as well as
      surgical and adjuvant treatment modalities have an impact on the functional
      outcome of patients' speech rehabilitation. It was the aim of this overview to
      specifiy speech and speech-related aspects as well as to delineate measurement
      methods of speech outcome in patients with oral cancer by a review of the
      literature. METHODS: The review is based on a Medline Search on "speech",
      "cancer", "oral cancer", "malignoma mouth", "intelligibility", "formant",
      "ultrasound". DISCUSSION: In particular, speech intelligibility is inevitable for
      the social interaction of patients which is highly correlated with the patient's
      quality of life. However, speech outcome measurement shows a variety of methods
      without an international standardisation. Additionally, several co-aspects of
      speech production have to be considered: tongue mobility, voice production,
      velopharyngeal closure and neural coordination are important influencing factors.
      Speech assessment is traditionally performed by perceptual methods on a
      subjective or semi-subjective base. More objective, technical-based methods of
      speech evaluation are in development and under research. PURPOSE: It was the aim
      of this overview to specify speech and speech-related aspects as well as to
      delineate measurement methods of speech outcome in patients with oral cancer by a
      review of the current literature.

PMID- 22864646
TI  - Novel immune signals and atherosclerosis.
AB  - Atherosclerosis underlies coronary artery disease (CAD) and cerebrovascular
      disease, which are the most common forms of life-threatening cardiovascular
      disorders. To minimize the risk of atherosclerotic complications, primary and
      secondary prevention strategies seek to control risk factors. Reducing low
      density lipoprotein (LDL) cholesterol through lipid-lowering drugs, such as
      statins, in particular yields a proportional decrease in cardiovascular disease
      risk. Atherosclerosis is considered to be a complex chronic inflammatory process
      triggered by cardiovascular risk factors which cause endothelial dysfunction and
      inflammatory cell infiltration within the artery wall. In this review, we
      summarize the current understanding of the underling molecular mechanisms of the
      immune signals in the development and progression of atherosclerosis. Among
      various molecular mechanisms, toll like receptors (TLRs) are potent
      proinflammatory cytokines that operate to induce inflammation play an important
      role in the pathogenesis of atherosclerosis. Moreover, we discuss current
      knowledge regarding monocyte/macrophage biology that contributes to the
      progression of atherosclerosis, including macrophage polarization and
      heterogeneity. Understanding the molecular mechanisms in conjunction with
      orchestration of monocyte/macrophage biology should provide a basis for novel
      treatment strategies to prevent the development and progression of
      atherosclerosis.

PMID- 22864647
TI  - A predictive model for neurodevelopmental outcome after the Norwood procedure.
AB  - Neurodevelopmental outcomes after the Norwood procedure for single right
      ventricular lesions are worse than those in the normal population. It would be
      valuable to identify which patients at the time of Norwood discharge are at
      greatest risk for neurodevelopmental impairment later in childhood. As such, this
      study sought to construct and validate a model to predict poor neurodevelopmental
      outcome using variables readily available to the clinician. Using data from the
      14 month neurodevelopmental outcome of the Single-Ventricle Reconstruction (SVR)
      trial, a classification and regression tree (CART) analysis model was developed
      to predict severe neurodevelopmental impairment, defined as a Psychomotor
      Development Index (PDI) score lower than 70 on the Bayley Scales of Infant
      Development-II. The model then was validated using data from subjects enrolled in
      the Infant Single Ventricle (ISV) trial. The PDI scores were lower than 70 for
      138 (44 %) of 313 subjects. Predictors of a PDI lower than 70 were post-Norwood
      intensive care unit (ICU) stay longer than 46 days, genetic syndrome or other
      anomalies, birth weight less than 2.7 kg, additional cardiac surgical procedures,
      and use of five or more medications at hospital discharge. Using these risk
      factors, the CART model correctly identified 75 % of SVR subjects with a PDI
      lower than 70. When the CART model was applied to 70 subjects from the ISV trial,
      the correct classification rate was 67 %. This model of variables from the
      Norwood hospitalization can help to identify infants at risk for
      neurodevelopmental impairment. However, given the overall high prevalence of
      neurodevelopmental impairment and the fact that nearly one third of severely
      affected children would not have been identified by these risk factors, close
      surveillance and assessment for early intervention services are warranted for all
      infants after the Norwood procedure.

PMID- 22864648
TI  - Impact of 22q11.2 deletion on the postoperative course of children after cardiac
      surgery.
AB  - The primary objective of this study was to describe the impact of 22q11.2
      deletion (del22q11) on the clinical characteristics, postoperative course, and
      short-term outcomes of children undergoing surgery for congenital heart disease.
      The charts of all children ages 1 day-18 years who received cardiac surgery for
      interrupted aortic arch (IAA), tetralogy of Fallot (TOF), or truncus arteriosus
      (TA) repair from 1 January 2001 to 31 December 2011 were retrospectively
      reviewed. The patients were divided into two groups: the 22q11 group including
      children with del22q11 undergoing surgery for TOF, IAA, or TA and the non-22q11
      or control group including children with no chromosomal or genetic abnormality
      undergoing surgery for TOF, IAA, or TA. Demographic information, cardiac
      diagnoses, noncardiac abnormalities, preoperative factors, intraoperative
      details, surgical procedures performed, postoperative complications, and in
      hospital deaths were collected. The outcome data collected included days of
      inotrope use, need for dialysis, length of mechanical ventilation, intensive care
      unit (ICU) length of stay (LOS), hospital LOS, and mortality. The study enrolled
      173 patients: 65 patients in the 22q11 group and 108 patients in the control
      group. Of the 65 patients in the 22q11 group, 36 (55 %) underwent repair for TOF,
      13 (20 %) for IAA, and 16 (25 %) for TA. The two groups did not differ in terms
      of age or weight. The preexisting conditions were similar in the two groups.
      Unplanned noncardiac operations were more common in the children with del22q11,
      but delayed chest closure was similar in the two groups. The incidence of
      postoperative noncardiac complications such as reintubation, vocal cord
      paralysis, and diaphragmatic paralysis was similar in the two groups. However,
      increasing numbers of patients in del22q11 group needed dialysis in one form or
      the other during the immediate postoperative stay. The incidence of fungal
      infection and wound infection was higher in the del22q11 group than in the
      control group. Duration of mechanical ventilation, ICU LOS, and hospital LOS were
      similar in the two groups, except in certain subgroups. Mortality did not differ
      significantly between the two groups. In conclusion, children with del22q11 have
      a higher risk of postoperative complications after cardiac surgery, with no
      difference in length of mechanical ventilation, ICU LOS, hospital LOS, or
      mortality. However, short-term outcomes may differ in certain subgroups.

PMID- 22864649
TI  - Synthesis of eugenol esters by lipase-catalyzed reaction in solvent-free system.
AB  - Enzymatic esterification of eugenol is a matter of great scientific and
      technological interest due to the well-known drawbacks of the chemical-catalyzed
      route as well as the potential use of produced compounds as natural
      antimicrobials. This work reports the maximization of eugenil acetate production
      by esterification of eugenol and acetic anhydride in a solvent-free system using
      Novozym 435 as catalyst. The antimicrobial activity of eugenol and eugenil
      acetate was also determined. The operating conditions that maximized eugenil
      acetate production were 50  degrees C, eugenol to acetic anhydride of 1:3, 150
      rpm, and 5.5 wt% of enzyme, with a conversion of 99 %. A kinetic study was
      performed to assess the influence of substrates molar ratio, enzyme
      concentration, and temperature on eugenil acetate yield. Results show that an
      excess of anhydride, low enzyme concentration (1 wt%), and 60  degrees C afforded
      nearly complete conversion after 6 h of reaction. The highest antimicrobial
      activity of eugenil acetate was observed against Acinetobacter sp. (48.66 mm) at
      concentration of 20 MUL. Results indicate that the esterification of eugenol
      improved its antimicrobial properties. New experimental data on enzymatic
      esterification of eugenol and acetic anhydride are reported in this work, showing
      a promising perspective to overcome the inconvenient of the chemical-catalyzed
      route for obtaining antimicrobial natural compounds.

PMID- 22864650
TI  - The groin first approach for transcatheter aortic valve implantation: are we
      pushing the limits for transapical implantation?
AB  - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) is a therapeutic option
      for old and multimorbid patients with severe aortic stenosis. When applying the
      groin first approach by transfemoral implantation, patients in the transapical
      group are highly selected with even higher morbidity. We report outcome of the
      transapical group. METHODS: Between April 2008 and May 2011, 267 patients
      underwent TAVI through either a transfemoral (n = 201 CoreValve, n = 33 Edwards
      Sapien prostheses; mean age 81 +/- 6 years, logistic EuroSCORE 19.5 +/- 12.6 %; 4
      76, STS score 7.2 +/- 4 %; 1.5-28.9) or transapical approach (n = 33 Edwards
      Sapien prostheses; mean age 80 +/- 1 years, logistic EuroSCORE 31.6 +/- 17.1 %;
      9.4-69.1, STS score 12.8 +/- 7.1 %; 2.5-28.8). The transapical access was chosen
      only when transfemoral implantation was not possible. RESULTS: EuroSCORE and STS
      score were significantly higher in the transapical group (p = 0.001,
      respectively). A 30-day survival was comparable with 87.9 % in the transapical
      versus 92 % in the transfemoral group (p = 0.52). In the transapical group,
      female gender was predominant (n = 23; 70 %). Eight patients underwent previous
      cardiac surgery. All transapical implantations were successful. No bleeding or
      neurological complications occurred. Six patients required postoperative
      pacemaker implantation. Cardiac decompensation with concomitant pneumonia was the
      underlying cause for early mortality, except for one patient with abdominal
      malperfusion. Follow-up (0-37 months) was complete in 100 %, nine patients died
      after 30 days postoperatively (6 cardiac and 3 non-cardiac related).
      Echocardiography revealed good valve function with not more than mild
      paravalvular incompetence. CONCLUSIONS: Groin first approach is reasonable due to
      less invasive implantation technique. However, despite even higher predicted
      mortality, transapical aortic valve implantation is non-inferior to transfemoral
      approach.

PMID- 22864651
TI  - Abuse and neglect of older persons in seven cities in seven countries in Europe:
      a cross-sectional community study.
AB  - OBJECTIVES: We aimed to investigate the prevalence rate of abuse (psychological,
      physical, sexual, financial, neglect) of older persons (AO) in seven cities from
      seven countries in Europe (Germany, Greece, Italy, Lithuania, Portugal, Spain,
      Sweden), and to assess factors potentially associated with AO. METHODS: A cross
      sectional study was conducted in 2009 (n = 4,467, aged 60-84). Potentially
      associated factors were grouped into domains (domain 1: age, gender, migration
      history; domain 2: education, occupation; domain 3: marital status, living
      situation; domain 4: habitation, income, financial strain). We calculated odds
      ratios (OR) with their respective 95 % confidence intervals (CI). RESULTS:
      Psychological AO was the most common form of AO, ranging from 10.4 % (95 % CI 8.1
      13.0) in Italy to 29.7 % (95 % CI 26.2-33.5) in Sweden. Second most common form
      was financial AO, ranging from 1.8 % (95 % CI 0.9-3.2) in Sweden to 7.8 % (95 %
      CI 5.8-10.1) in Portugal. Less common was physical AO, ranging from 1.0 % (95 %
      CI 0.4-2.1) in Italy to 4.0 % (95 % CI 2.6-5.8 %) in Sweden. Sexual AO was least
      common, ranging from 0.3 (95 % CI 0.0-1.1) in Italy and Spain to 1.5 % (95 % CI
      0.7-2.8) in Greece. Being from Germany (AOR 3.25, 95 % CI 2.34-4.51), Sweden (OR
      3.16, 95 % CI 2.28-4.39) or Lithuania (AOR 2.45, 95 % CI 1.75-3.43) was
      associated with increased prevalence rates of AO. CONCLUSION: Country of
      residence of older people is independent from the four assessed domains
      associated with AO. Life course perspectives on AO are highly needed to get
      better insight, and to develop and implement prevention strategies targeted at
      decreasing prevalence rates of AO.

PMID- 22864652
TI  - Differing lifecourse associations with sport-, occupational- and household-based
      physical activity at age 49-51 years: the Newcastle Thousand Families Study.
AB  - OBJECTIVES: We investigated the contributions of a range of factors from across
      life to variations in physical activity within the Newcastle Thousand Family's
      birth cohort. METHODS: At age 49-51 years, 574 study members returned
      questionnaires, including details of physical activity (occupational, commuting,
      household and sport). Factor analysis of activity types produced two retained
      factor scores, 'sport' and 'other physical activity', analysed by path analysis.
      RESULTS: More advantaged current social class, higher education level and not
      smoking were associated with increased sport activity, but not 'other physical
      activity'. Males had higher levels of occupational and lower levels of household
      activity than females. Smokers had increased work activity. Long-term illness was
      associated with lower activity across all types. Current social class and smoking
      showed the highest relative contribution for 'sport' and long-term illness for
      'other physical activity'. CONCLUSION: Increasing activity in adults requires
      better understanding what the barriers to maintaining or taking on new levels of
      physical activity are, and long-term strategies and public health interventions
      need to be developed to engage adults in interesting, affordable and available
      activities.

PMID- 22864654
TI  - Severe acute asthma attack in a child complicated by tracheal tube malposition.

PMID- 22864653
TI  - The preconditioning pulmonary protective effect of volatile isoflurane in acute
      lung injury is mediated by activation of endogenous iNOS.
AB  - PURPOSE: There is still a lack of evidence to support the use of specific
      anesthetic agents during major operations that could affect the development of
      postoperative acute lung injury (ALI). This study determined the protective
      effect of inhaled isoflurane in a rat model of endotoxin-induced ALI. METHODS:
      Rats were exposed to volatile isoflurane (1.5 % in oxygen) or pure oxygen via a
      facemask for 2 h. After a 3-h recovery period, rats were reanesthetized and ALI
      was induced by intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg in
      0.5 ml saline). In some animals, a specific inducible nitric oxide synthase
      (iNOS) inhibitor, 1400W, (10 mg/kg, i.p.) was administered before exposure to
      isoflurane. Animals were sacrificed 12 h later for analysis. Pulmonary artery
      vasomotor function and alveolocapillary permeability were assessed. Expression of
      iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed.
      RESULTS: The maximal relaxation response to acetylcholine was significantly
      potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced
      in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were
      attenuated in the lung tissue obtained from rats receiving isoflurane.
      Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung
      preexposed to isoflurane. However, these pulmonary protective effects of
      isoflurane were significantly abolished by pretreatment with 1400W. CONCLUSION:
      Pretreatment with volatile isoflurane attenuated inflammatory process in the lung
      tissue of rats with LPS-induced ALI, and this preconditioning pulmonary
      protective effect was mainly mediated by activation of endogenous iNOS in the
      lung.

PMID- 22864655
TI  - How does Arabic orthographic connectivity modulate brain activity during visual
      word recognition: an ERP study.
AB  - One of the unique features of the Arabic orthography that differentiates it from
      many other alphabetical ones is the fact that most letters connect obligatorily
      to each other. Hence, these letters change their forms according to the location
      in the word (i.e. beginning, middle, or end), leading to the suggestion that
      connectivity adds a visual load which negatively impacts reading in Arabic. In
      this study, we investigated the effects of the orthographic connectivity on the
      time course of early brain electric responses during the visual word recognition.
      For this purpose, we collected event-related potentials (ERPs) from adult skilled
      readers while performing a lexical decision task using fully connected (Cw),
      partially connected and non-connected words (NCw). Reaction times variance was
      higher and accuracy was lower in NCw compared to Cw words. ERPs analysis revealed
      significant amplitude and latency differences between Cw and NCw at posterior
      electrodes during the N170 component which implied the temporo-occipital areas.
      Our findings show that instead of slowing down reading, orthographic connectivity
      in Arabic skilled readers seems to impact positively the reading process already
      during the early stages of word recognition. These results are discussed in
      relation to previous observations in the literature.

PMID- 22864656
TI  - [Vertebral stability in management of spinal metastases. Criteria and strategies
      for operative interventions].
AB  - BACKGROUND: Metastases are responsible for most tumor manifestations of the
      spine. About 25% are symptomatic; however, due to interdisciplinary management
      the tumor-associated mortality is regressing. Associated acute spinal cord injury
      (SCI) syndromes raise patient morbidity with a loss of independence and quality
      of life associated with a fair potential for recovery. Therefore, the management
      is focused on the avoidance of SCI. The assessment of mechanical stability of
      vertebral bodies is a central part of decision-making when considering operative
      therapy. This review gives an update on the current evidence-based data for
      metastasis management. DECISION MAKING: The NOMS concept is well established.
      Especially the parameters origin, neurologic symptoms, stability and
      vascularization are described and illustrated by clinical cases. OPERATIVE
      THERAPY CONCEPTS: Evidence-based operative therapy concepts are shown reflecting
      palliative and curative approaches. ASSESSMENT OF PARAMETERS FOR THERAPY
      ALGORITHM: Clinical and radiological parameters help to find the individual
      therapy. Generally a number of scores with significant time expenditure are
      needed. The spine instability neoplastic score (SINS) simplifies the management.
      Operative therapy shows the best results for the parameters pain and quality of
      life. However, potential perioperative and postoperative complications have to be
      estimated and should be avoided. Using these facts our therapy algorithm is
      helpful for therapy management. CONCLUSIONS: With rising life expectancy
      operative therapy is of increasing relevance. Decision-making uses information
      about tumor origin, neurologic symptoms, stability, prognostic factors and
      vascularisation to determine the individual therapy.

PMID- 22864657
TI  - [Biomechanical aspects of complex reconstructions following radical resection of
      thoracolumbar spinal tumors].
AB  - The total number of spinal tumors has increased over the past decade. However,
      the average survival time of tumor patients has increased due to improvements in
      the multidisciplinary treatment regimes. Therefore, radical tumor resection and
      complex reconstruction were developed in spinal surgery. Various reconstructive
      options for the throracolumbar spine are nowadays available and are depicted in
      this article. The success of complex reconstructive surgery relies on
      biomechanical principles and reconstruction is dependent on the size and location
      of the lesion, bone porosity and implant systems used. Special emphasis of this
      article focuses on en bloc vertebrectomy which is the most radical approach of
      spinal tumor surgery. The biomechanical aspects of different types of lesions and
      the reconstructive options are discussed in the context of the currently
      published literature.

PMID- 22864658
TI  - [Challenges and characteristics of spondylodiscitis of the cervical spine].
AB  - The human cervical spine is a unique structure that differs dramatically from the
      thoracic and lumbar spine. The main differences concern the topographic anatomy
      of the spinal cord, anatomy and physiology of the occipito-atlanto-axial joint
      complex, the close course of the vertebral artery to the cervical spine and the
      very close relationship of the esophagus, vessels, peripheral and cranial nerves
      to the spine. To avoid serious complications during surgical treatment of
      spondylodiscitis within the cervical spine, these aspects must be kept in mind.
      They will be explained in detail in this article.

PMID- 22864659
TI  - [Joint-preserving surgery of the adult hip. Intertrochanteric femoral osteotomy].
AB  - Due to advances in total joint replacement, intertrochanteric osteotomy (ITO) is
      performed more infrequently in spite of good clinical results. Nevertheless,
      there are several good indications for this joint-preserving procedure in adults.
      Detailed biomechanical knowledge and precise clinical examination are
      prerequisites for correct indications and planning of ITO. The main target of
      this surgical procedure is improvement of joint congruency and normalization of
      load transfer to protect damaged cartilage. Very good results can be obtained in
      hip dysplasia, non-union of the femoral neck and proximal femoral deformities if
      the therapeutic principles are followed. Higher failure rates have to be expected
      in femoral head necrosis and osteoarthritis, depending on the degree of pre
      existing cartilage damage.

PMID- 22864660
TI  - Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch
      syndrome founder mutation.
AB  - Founder mutations with a large impact in distinct populations have been described
      in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT
      mutation accounts for 25 % of the MLH1 mutant families. We used the national
      Danish hereditary nonpolyposis colorectal cancer register to estimate the
      cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder
      mutation families with comparison to 47 other MLH1 mutant families. The founder
      mutation conferred comparable risks for colorectal cancer (relative risks, RR, of
      0.99 for males and 0.79 for females) and lower risks for extracolonic cancer (RR
      of 0.69 for endometrial cancer and 0.39 for all other extracolonic cancers). We
      also characterized expression of key Wnt-signaling proteins in colorectal cancers
      with the founder mutation. Aberrant staining affected beta-catenin in 59 %, E
      cadherin in 68 %, TCF-4 in 94 % and Cyclin D1 in 68 % with extensive inter-tumor
      variability despite the same underlying germline mutation. In conclusion, the
      Danish MLH1 founder mutation that accounts for a significant proportion of Lynch
      syndrome and is associated with a lower risk for extracolonic cancers.

PMID- 22864662
TI  - Mixed ligand palladium(II) complexes of 6-methoxy-2-oxo-1,2-dihydroquinoline-3
      carbaldehyde 4N-substituted thiosemicarbazones with triphenylphosphine co-ligand:
      synthesis, crystal structure and biological properties.
AB  - A series of new 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4N
      substituted thiosemicarbazone ligands (H2L1-H2L5) and their corresponding
      palladium(II) complexes [Pd(L1)(PPh3)] (1), [Pd(L2)(PPh3)] (2), [Pd(HL3)(PPh3)]Cl
      (3), [Pd(L4)(PPh3)] (4) and [Pd(L5)(PPh3)] (5), have been synthesized in order to
      evaluate the effect of terminal N-substitution in thiosemicarbazone moiety on
      coordination behaviour and biological activity. The new ligands and their
      corresponding complexes were characterized by analytical and various spectral
      techniques. The molecular structure of the complexes 2-5 were characterized by
      single crystal X-ray diffraction studies which revealed that the ligands H2L2,
      H2L4 and H2L5 are coordinated to palladium(II) as binegative tridentate (ONS2-)
      by forming six and five member rings whereas, the ligand H2L3 coordinated to
      Pd(II) as uninegative tridentate (ONS-). The interactions of the new complexes
      with calf thymus DNA (CT-DNA) have been evaluated by absorption and ethidium
      bromide (EB) competitive studies which revealed that complexes 1-5 could interact
      with CT-DNA through intercalation. Further, the interactions of the complexes
      with bovine serum albumin (BSA) were also investigated using UV-visible,
      fluorescence and synchronous fluorescence spectroscopic methods, which showed
      that the new complexes could bind strongly with BSA. Antioxidant studies showed
      that all the complexes have a strong antioxidant activity against 2-2'-diphenyl-1
      picrylhydrazyl (DPPH) radical and 2,2'-azino-3-ethylbenzthiazoline-6-sulfonic
      acid diammonium salt (ABTS) cation radical. In addition, in vitro cytotoxicity of
      the complexes against human lung cancer (A549) cell line was assayed which showed
      that 4 has higher cytotoxic activity than the rest of the complexes and
      cisplatin.

PMID- 22864661
TI  - Identification of a novel NBN truncating mutation in a family with hereditary
      prostate cancer.
AB  - Nibrin (NBN), located on chromosome 8q21 is a gene involved in DNA double-strand
      break repair that has been implicated in the rare autosomal recessive chromosomal
      instability syndrome known as Nijmegen Breakage Syndrome (NBS). NBS is
      characterized by specific physical characteristics (microcephaly and dysmorphic
      facies), immunodeficiency, and increased risk of malignancy. Individuals who are
      heterozygous for NBN mutations are clinically asymptomatic, but may display an
      elevated risk for certain cancers including, but not limited to, ovarian and
      prostate cancer as well as various lymphoid malignancies. In this study, 94
      unrelated familial prostate cancer cases from the University of Michigan Prostate
      Cancer Genetics Project (n = 54) and Johns Hopkins University (n = 40) were
      subjected to targeted next-generation sequencing of the exons, including UTRs, of
      NBN. One individual of European descent, diagnosed with prostate cancer at age
      52, was identified to have a heterozygous 2117 C > G mutation in exon 14 of the
      gene, that results in a premature stop at codon 706 (S706X). Sequencing of
      germline DNA from additional male relatives showed partial co-segregation of the
      NBN S706X mutation with prostate cancer. This NBN mutation was not observed among
      2768 unrelated European men (1859 with prostate cancer and 909 controls). NBN is
      involved in double-strand break repair as a component of the MRE11 (meiotic
      recombination 11)/RAD50/NBN genomic stability complex. The S706X mutation
      truncates the protein in a highly conserved region of NBN near the MRE11 binding
      site, thus suggesting a role for rare NBN mutations in prostate cancer
      susceptibility.

PMID- 22864663
TI  - Spontaneous emission of singlet oxygen near dielectric nano-objects and radiative
      diagnostics of bio-objects.
AB  - We investigate modifications of a spontaneous emission rate near the surface of
      the hemoglobin-like dielectric structure in the long-wavelength limit. We
      demonstrate that notwithstanding the small size of the dielectric structure, an
      influence of its shape cannot be neglected. Even for moderate dielectric
      contrasts one can expect having significant and detectable enhancement or
      suppression of the spontaneous emission rate near the surface of the biological
      macromolecule.

PMID- 22864665
TI  - Preclinical evaluation of a novel c-Met inhibitor in a gastric cancer xenograft
      model using small animal PET.
AB  - PURPOSE: Here, we describe the efficacy of the novel small molecule c-Met
      inhibitor BAY 853474 in reducing tumor growth in the Hs746T gastric cancer
      xenograft model and tested the suitability of 2-deoxy-2-[(18)F]fluoro-D-glucose
      ([(18)F]FDG) versus 3'-deoxy-3'-18F-fluorothymidine ([(18)F]FLT) for response
      monitoring in a gastric cancer xenograft mouse model using small animal PET.
      PROCEDURES: The c-Met inhibitor or vehicle control was administered orally at
      various doses in tumor-bearing mice. Glucose uptake and proliferation was
      measured using PET before, 48 and 96 h after the first treatment. The PET data
      were compared to data from tumor growth curves, autoradiography, Glut-1 and Ki-67
      staining of tumor sections, and biochemical analysis of tissue probes, i.e., c
      Met and ERK phosphorylation and cyclin D1 levels. RESULTS: BAY 853474
      significantly reduces tumor growth. [(18)F]FDG uptake in Hs746T tumors was
      significantly reduced in the groups receiving the drug, compared with the control
      group. The [(18)F]FLT uptake in the tumor tissue was completely absent 96 h after
      treatment. Autoradiographic, immunohistochemical, and biochemical analyses
      confirmed the PET findings. Treatment with the c-Met inhibitor did not affect
      body weight or glucose levels, and no adverse effects were observed in the
      animals. CONCLUSION: These preclinical findings suggest that clinical PET imaging
      is a useful tool for early response monitoring in clinical studies.

PMID- 22864667
TI  - Dual-core optofluidic chip for independent particle detection and tunable
      spectral filtering.
AB  - We present the first integration of fluidically tunable filters with a separate
      particle detection channel on a single planar, optofluidic chip. Two optically
      connected, but fluidically isolated liquid-core antiresonant reflecting optical
      waveguide (ARROW) segments serve as analyte and spectral filter sections,
      respectively. Ultrasensitive detection of fluorescent nanobeads with high signal
      to-noise ratio provided by a fluidically tuned excitation notch filter is
      demonstrated. In addition, reconfigurable filter response is demonstrated using
      both core index tuning and bulk liquid tuning. Notch filters with 43 dB rejection
      ratio and a record 90 nm tuning range are implemented by using different mixtures
      of ethylene glycol and water in the filter section. Moreover, absorber dyes and
      liquids with pH-dependent transmission in the filter channel provide additional
      spectral control independent of the waveguide response. Using both core index and
      pH control, independent filter tuning at multiple wavelengths is demonstrated for
      the first time. This extensive on-chip control over spectral filtering as one of
      the fundamental components of optical particle detection techniques offers
      significant advantages in terms of compactness, cost, and simplicity, and opens
      new opportunities for waveguide-based optofluidic analysis systems.

PMID- 22864666
TI  - Combination of tagging and tissue phase mapping to accelerate myocardial motion
      measurements in three directions.
AB  - OBJECT: Until now, a three-directional velocity field has mostly been obtained by
      velocity encoding in three directions, which is very time-consuming and hence not
      usually used in clinical routine. We show the feasibility of combining in-plane
      tagging with through-plane tissue phase mapping (TPM) to encode a three
      directional velocity field at 3 T with reduced overall acquisition time.
      MATERIALS AND METHODS: Assessment of a three-directional velocity field was
      performed for 10 healthy volunteers. The motion patterns obtained by use of five
      different sequences including three-directional TPM, TPM in the through-plane
      direction, TPM in the through-plane direction with horizontal or vertical tagging
      lines, and TPM in the through-plane direction combined with a tagging grid were
      evaluated and compared. RESULTS: A three-dimensional velocity field can be
      obtained in approximately half the acquisition time by combining through-plane
      TPM with in-plane tagging. Although the velocity information is derived by
      different means, differences between the information obtained by three
      directional TPM encoding and the suggested technique are only minor. CONCLUSION:
      The combination of tagging and TPM enables assessment of the three-directional
      velocity field in nearly half the time taken when the conventional three
      directional TPM sequence is used.

PMID- 22864669
TI  - International veterinary bioequivalence guideline similarities and differences
      between Australia, Canada, Europe, Japan, New Zealand and the United States.
AB  - Considering the diversity in physiology between species and the numerous dosage
      forms that exist in veterinary drug products, there are numerous complex issues
      that arise from the development and regulation of veterinary drugs for food
      producing and companion animals. Generic drugs are no exception. The main
      objective of this article is to illustrate the current important similarities and
      differences between international veterinary bioequivalence guidelines. It is
      concluded that since important differences are found, these may lead to barriers
      in international data exchange and scientific confusion, hence fostering the need
      for a harmonization effort in developing consistent guidelines based on sound
      pharmacological and statistical principles for the approval of veterinary generic
      drugs around the world.

PMID- 22864668
TI  - Challenges and opportunities in absorption, distribution, metabolism, and
      excretion studies of therapeutic biologics.
AB  - With the advancement of biotechnology in the last two decades, optimized and
      novel modalities and platforms of biologic moieties have emerged rapidly in drug
      discovery pipelines. In addition, new technologies for delivering therapeutic
      biologics (e.g., needle-free devices, nanoparticle complexes), as well as novel
      approaches for disease treatments (e.g., stem cell therapy, individualized
      medicine), continue to be developed. While pharmacokinetic studies are routinely
      carried out for therapeutic biologics, experiments that elucidate underlying
      mechanisms for clearance and biodistribution or identify key factors that govern
      absorption, distribution, metabolism, and excretion (ADME) of biologics often are
      not thoroughly conducted. Realizing the importance of biologics as therapeutic
      agents, pharmaceutical industry has recently begun to move the research focus
      from small molecules only to a blended portfolio consisting of both small
      molecules and biologics. This trend brings many opportunities for scientists
      working in the drug disposition research field. In anticipation of these
      opportunities and associated challenges, this review highlights impact of ADME
      studies on clinical and commercial success of biologics, with a particular focus
      on emerging applications and technologies and linkage with mechanistic
      pharmacokinetic/pharmacodynamic modeling and biomarker research.

PMID- 22864670
TI  - Double ophthalmic arteries arising from the internal carotid artery.
AB  - Rarely, the ophthalmic artery (OA) arises from the cavernous segment of the
      internal carotid artery (ICA) inferolaterally and enters into the orbit via the
      superior orbital fissure. This anomalous OA that originates from the
      inferolateral trunk is regarded as a persistent dorsal OA. Extremely rarely, both
      normal OA and persistent dorsal OA arise from the ICA. We report the first case
      of such double OAs, one of which arose from the cavernous segment of the ICA
      superolaterally and we believe that it originated from the meningohypophyseal
      trunk rather than the inferolateral trunk.

PMID- 22864671
TI  - Overexpression of HOXA1 correlates with poor prognosis in patients with
      hepatocellular carcinoma.
AB  - HOXA1 overexpression is sufficient for malignant transformation of nontumorigenic
      epithelial cells. It is known that HOXA1, which was upregulated in squamous cell
      carcinomas, affects both cell growth and death. The forced expression of HOXA1 in
      human breast cancer cells results in increased cell growth activity. However, it
      has not been reported in hepatocellular carcinoma (HCC). In this study, we used
      immunohistochemistry to compare HOXA1 protein expression in HCC and normal liver
      tissues and further analyzed HOXA1 protein expression in 156
      clinicopathologically characterized HCC cases. We stably knocked down the
      endogenous expression level of HOXA1 in HepG2 cells with specific shRNA
      expressing lentiviral vector. Following the successful establishment of stable
      cells, we examined in vitro cell growth by the MTT assay, anchorage-independent
      growth through a soft agar colony formation assay and cell migration/invasion by
      transwell and Boyden chamber assay. In addition, we also investigated in vivo
      tumor growth by xenograft transplantation of HepG2 cells into nude mice. Our
      results showed that the protein expression level of HOXA1 was markedly higher in
      HCC tissues than that in normal liver tissue (P = 0.019). In addition, a high
      expression level of HOXA1 protein was positively correlated with the T
      classification (P < 0.001), the N classification (P < 0.001), distant metastasis
      (P = 0.004), and the clinical stage (P < 0.001) of HCC patients. Patients with
      higher HOXA1 expression showed a significantly shorter overall survival time
      compared with patients with low HOXA1 expression. Multivariate analysis suggested
      that HOXA1 expression might be an independent prognostic indicator (P < 0.001)
      for the survival of patients with HCC. HOXA1-specific shRNA (shHOXA1)
      successfully knocked down HOXA1 endogenous expression in HepG2 cells. Compared to
      the parental and control shRNA-transfected (shCtrl) HepG2 cells, the shHOXA1
      cells exhibited significantly reduced in vitro cell growth, anchorage-independent
      growth, and cell migration and invasion (P < 0.05). In vivo, the xenograft
      transplants from shHOXA1 cells gave rise to much smaller tumors compared with
      those from shCtrl cells. Collectively, high HOXA1 expression is associated with
      poor overall survival in patients with HCC. The downregulation of HOXA1 inhibits
      growth, anchorage-independent growth, and migration and invasion of HepG2 cells.

PMID- 22864673
TI  - Three diiron complexes bearing an aromatic ring as mimics of the diiron subunit
      of [FeFe]-hydrogenase: synthesis, electron transfer and coupled chemical
      reactions.
AB  - Three diiron complexes (1-Ph, 2-OH, and 3-OCOFc) as mimics of the diiron subunit
      of [FeFe]-hydrogenase were electrochemically investigated in 0.1 mol L(-1)
      [NBut(4)]BF(4)-acetonitrile (MeCN) under CO and Ar atmosphere. Complex 3-OCOFc
      was prepared from the reaction of complex 2-OH with ferrocenylacyl chloride
      (FcOCCl). The complex was fully characterised using a variety of spectroscopic
      techniques. Its structure was established using X-ray single crystal diffraction
      analysis. In addition to the well-established ECE (E for electrochemical and C
      for chemical) mechanism, it was revealed that a further reversible reduction at a
      potential more negative by ca. 600 mV was observed under CO atmosphere. It was
      further proposed based on the analysis of electrochemical and infrared
      spectroscopic data that the second redox was due to a two-electron process of
      supposedly a tetrairon cluster. This product was formed in situ from the reaction
      between the dianion generated from the ECE process and its parent complex (1-Ph,
      2-OH, and 3-OCOFc) and is supposedly of a core "Fe(4)(II)". This reaction
      occurred only when CO was presented. Under Ar atmosphere, bulk electrolysis led
      to fully-reduced products, that is, with the iron at the oxidation state of zero,
      but complex was an exception. An overall mechanism to describe the electron
      transfer and coupled chemical reactions under CO atmosphere was proposed.

PMID- 22864672
TI  - Current concepts and controversies in prevention and treatment of diabetic
      ketoacidosis in children.
AB  - Diabetic ketoacidosis (DKA) is caused by absolute or relative lack of insulin.
      Lack of insulin leads to hyperglycemia, ketonemia, and acidosis. Prevalence of
      DKA at diagnosis of type 1 diabetes (T1D) varies around the world from 18 % to 84
      %. Incidence of recurrent DKA is higher among females, insulin pump users, those
      with a history of psychiatric or eating disorder, and suboptimal socioeconomic
      circumstances. DKA is the most common cause of death in children with T1D.
      Children with DKA should be treated in experienced centers. Initial bolus of 10
      20 mL/kg 0.9 % saline is followed by 0.45 %-0.9 % saline infusion. Fluid infusion
      should precede insulin administration (0.1 U/kg/h) by 1-2 hours. The prevention
      of DKA at diagnosis of diabetes can be achieved by an intensive community
      intervention and education of health care providers to raise awareness.
      Prevention of recurrent DKA requires continuous patient education and access to
      diabetes programs and telephone services.

PMID- 22864674
TI  - Closure of an aortopulmonary window using the Amplatzer Duct Occluder II.
AB  - We report two cases of transcatheter-device closure of aortopulmonary windows, a
      residual defect occurring after previous surgical closure, and a native lesion.
      The postsurgical defect was closed with an Amplatzer Duct Occluder II (AGA
      Medical Corporation, MN). The native lesion was not suitable for an Amplatzer
      Duct Occluder II device; thus, it was closed using an Amplatzer Duct Occluder
      (AGA Medical Corporation, MN). The Amplatzer Duct Occluder II provides an
      additional device for aortopulmonary window closure, but anatomy and defect
      characteristics dictate the most appropriate device.

PMID- 22864675
TI  - Sildenafil and ventriculo-arterial coupling in Fontan-palliated patients: a
      noninvasive echocardiographic assessment.
AB  - The fundamental role of pulmonary vascular resistance in the Fontan circulation
      is obvious. Medications decreasing this resistance may have an impact on the fate
      of this population. Hence, we assessed noninvasively the effect of oral
      sildenafil on the ventriculo-arterial coupling in patients with Fontan
      circulation. In a single-center, prospective case series study, 23 patients with
      fenestrated extracardiac total cavopulmonary connection age 12-31 years were
      enrolled in this study. Clinical characteristics and echocardiographic
      examination were performed before and after a 1 week course of sildenafil at 0.5
      mg/kg every 8 h. Sildenafil had no effect on heart rate and blood pressure.
      However, oxygen saturation was significantly increased with sildenafil (87.6 +/-
      4.3 vs. 90.1 +/- 3.6; P < 0.0001). The calculated noninvasive ventricular end
      systolic elastance (Ees) was greater after sildenafil compared with the pre
      sildenafil values (1.59 +/- 0.17 vs. 1.72 +/- 0.27 mm Hg/ml; P = 0.001).
      Moreover, significant decreases in arterial elastance (Ea) (1.62 +/- 0.53 vs.
      1.36 +/- 0.43 mm Hg/ml; P < 0.0001), ventricular end-diastolic elastance (Eed)
      (0.05 +/- 0.021 vs. 0.04 +/- 0.013; P = 0.002), and, finally, ventriculo-arterial
      coupling index (0.99 +/- 0.26 vs. 0.76 +/- 0.15; P < 0.0001) were found after
      sildenafil administration. The intolerable side effects that led to stopping the
      sildenafil occurred only in one (4 %) patient. Sildenafil has increased
      ventricular systolic elastance and improved ventriculo-arterial coupling in
      patients palliated with Fontan circulation. Short-term sildenafil was well
      tolerated in most of the patients with only minor side effects.

PMID- 22864676
TI  - Unusual clinical presentation of rare adult survivors with a missing pulmonary
      valve associated with a missing left pulmonary artery.
AB  - Tetralogy of Fallot with absent pulmonary valve syndrome is associated with
      absence of the left pulmonary artery in one-seventh of cases. Infants with this
      disorder commonly present very early in life with respiratory distress and heart
      failure. Because the pulmonary blood flow is primarily to the right lung only,
      severe respiratory distress occurs. Survival to late childhood without surgery is
      very rare due to clinical worsening in infancy. This report describes two adult
      natural survivors with this rare association who presented with extremely unusual
      unreported clinical features. The aneurysmally dilated main pulmonary artery was
      compressed on the left coronary ostium, causing angina in the first patient. The
      second patient had recurrent ventricular tachycardia originating from the dilated
      thinned out right ventricular outflow tract. Both patients had successful
      surgical correction with valved xenograft conduits.

PMID- 22864677
TI  - Prenatal images of the truncus arteriosus with an interrupted aortic arch.

PMID- 22864678
TI  - Culture of human bone marrow-derived mesenchymal stem cells on of poly(L-lactic
      acid) scaffolds: potential application for the tissue engineering of cartilage.
AB  - PURPOSE: Due to the attractive properties of poly(L-lactic acid) (PLLA) for
      tissue engineering, the aim was to determine the growth and differentiation
      capacity of mesenchymal stromal cells (MSCs) in PLLA scaffolds and their
      potential use in the treatment of cartilage diseases. METHODS: MSCs were cultured
      in PLLA films and thin porous membranes to study adherence and proliferation.
      Permeability and porosity were determined for the different scaffolds employed.
      The optimal conditions for cell seeding were first determined, as well as cell
      density and distribution inside the PLLA. Scaffolds were then maintained in
      expansion or chondrogenic differentiation media for 21 days. Apoptosis,
      proliferation and chondrogenic differentiation was assessed after 21 days in
      culture by immunohistochemistry. Mechanical characteristics of scaffolds were
      determined before and after cell seeding. RESULTS: MSCs uniformly adhered to PLLA
      films as well as to porous membranes. Proliferation was detected only in
      monolayers of pure PLLA, but was no longer detected after 10 days. Mechanical
      characterization of PLLA scaffolds showed differences in the apparent compression
      elastic modulus for the two sizes used. After determining high efficiencies of
      seeding, the production of extracellular matrix (ECM) was determined and
      contained aggrecan and collagens type I and X. ECM produced by the cells induced
      a twofold increase in the apparent elastic modulus of the composite. CONCLUSIONS:
      Biocompatible PLLA scaffolds have been developed that can be efficiently loaded
      with MSCs. The scaffold supports chondrogenic differentiation and ECM deposition
      that improves the mechanics of the scaffold. Although this improvement does not
      met the expectations of a hyaline-like cartilage ECM, in part due to the lack of
      a mechanical stimulation, their potential use in the treatment of cartilage
      pathologies encourages to improve the mechanical component.

PMID- 22864679
TI  - Relationship between femoroacetabular contact areas and hip position in the
      normal joint: an in vitro evaluation.
AB  - PURPOSE: Different approaches have been proposed to diagnose femoroacetabular
      impingement (FAI) condition and hip instability. It is still debatable which test
      is the most effective to make a correct diagnosis. The true mechanics of the hip
      during particular physical examination manoeuvres is unknown. METHODS: Eight
      fresh frozen hips were passively taken through 3 different commonly used
      positions for FAI diagnosis and hip instability: 90 degrees  Flexion-Adduction
      Internal Rotation, Hyperextension-Adduction-External Rotation and Hyperextension
      Neutral-External Rotation. Kinematics and anatomical data were acquired by an
      optoelectronic system. The contact areas between acetabulum and femoral head were
      analysed to determine whether these tests are able to localize regions of the hip
      that may give patients pain. RESULTS: In the hip positions where the femur was in
      Hyperextension-External Rotation, the contact area was mainly concentrated in the
      posterosuperior area of the acetabulum, while during 90 degrees  Flexion
      Adduction-Internal Rotation position, there was a wider distribution of contact,
      not specific to the anterolateral acetabulum. CONCLUSIONS: The results confirm
      the ability of the Hyperextension-External Rotation tests to particularly analyse
      the posterior region of the acetabulum. Placing the hip in 90 degrees  of Flexion
      Adduction-Internal Rotation allows for testing a wider zone of the acetabulum and
      is not specific to abutment of the femoral head-neck region against the
      anterolateral acetabulum.

PMID- 22864680
TI  - Manipulation under anaesthesia versus low stretch device in poor range of motion
      after TKA.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of two
      frequently used non-operative treatment techniques for a stiff knee after total
      knee arthroplasty. METHODS: Sixty-four patients with a stiff knee after total
      knee arthroplasty (TKA) were randomized into a manipulation under anaesthesia
      group, or a low load stretch (stretch) group. The patients were followed up for 6
      weeks and were evaluated for maximum flexion and extension, range of motion
      (ROM), pain, stiffness and function. RESULTS: Both groups showed a significant
      increase in knee flexion in this study. Only the stretch group showed a
      significant increase in extension ROM. In both groups, a significant increase in
      Western Ontario and McMaster Universities was observed. No significant difference
      was observed between both groups for the flexion or extension ROM, or for any of
      the pain, function or stiffness scores during this study. CONCLUSIONS: The
      results of this study showed that the stretch technique had equal or superior
      results concerning ROM and function compared to manipulation under anaesthesia.
      The stretch technique achieved this without requiring the patient to undergo in
      hospital treatment or anaesthesia, limiting the costs and the risks for
      complications. The results of this study showed that stretching is a valuable
      tool for treating joint contractures of the knee. Therefore, the use of this
      stretching technique may be an excellent first choice of treatment modality in
      patients with slow progress of knee flexion or persistent knee stiffness
      following TKA, prior to manipulation under anaesthesia or lysis of adhesions.

PMID- 22864682
TI  - A multi-case report of the pathways to and through genetic testing and cancer
      risk management for BRCA mutation-positive women aged 18-25.
AB  - Much of the extant literature addressing the psychosocial aspects of BRCA1/2
      mutation testing and risk management aggregates mutation carriers of all ages in
      study recruitment, data analysis, and interpretation. This analytic strategy does
      not adequately address the needs of the youngest genetic testing consumers, i.e.,
      women aged 18-25. Despite low absolute cancer risk estimates before age 30,
      BRCA1/2 mutation-positive women aged 18-25 feel vulnerable to a cancer diagnosis
      but find themselves in a management quandary because the clinical utility of
      screening and prevention options are not yet well defined for such young
      carriers. We present three cases, selected from a larger study of 32 BRCA1/2
      mutation-positive women who completed or considered genetic testing before age
      25, to demonstrate the unique developmental, relational and temporal influences,
      as well as the challenges, experienced by very young BRCA mutation-positive women
      as they complete genetic testing and initiate cancer risk management. The first
      case describes the maturation of a young woman whose family participated in a
      national cancer registry. The second addresses the experiences and expectations
      of a young woman who completed genetic testing after learning that her unaffected
      father was a mutation carrier. The third case highlights the experiences of a
      young woman parentally bereaved in childhood, who presented for genetic
      counseling and testing due to intense family pressure. Together, these cases
      suggest that BRCA1/2-positive women aged 18-25 are challenged to reconcile their
      burgeoning independence from their families with risk-related support needs.
      Loved ones acting in ways meant to care for these young women may inadvertently
      apply pressure, convoluting family support dynamics and autonomous decision
      making. Ongoing support from competent healthcare professionals will enable these
      young women to remain informed and receive objective counsel about their risk
      management decisions.

PMID- 22864681
TI  - Genetic background, gender, age, body temperature, and arterial blood pH have a
      major impact on myocardial infarct size in the mouse and need to be carefully
      measured and/or taken into account: results of a comprehensive analysis of
      determinants of infarct size in 1,074 mice.
AB  - In order to determine whether the myocardial response to ischemia/reperfusion
      (I/R) injury varies depending on genetic background, gender, age, body
      temperature, and arterial blood pH, we studied 1,074 mice from 19 strains
      (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J,
      B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA,
      C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H
      [ICR]) and distributed them into 69 groups depending on strain and: (1) two
      phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time;
      (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7)
      arterial blood pH. Mice underwent O either without (non-preconditioned [naive])
      or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4
      min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min
      O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was
      infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N
      mice had infarct sizes significantly smaller than those of the other mice. All
      strains except FVB/N benefited from the cardioprotection afforded by the early
      phase of PC; in contrast, development of LPC was inconsistent amongst groups and
      was strain-dependent. Female gender (1) was associated with reduced infarct size
      in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited
      the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 
      degrees C decrease in core temperature) and mild acidosis (0.18 decrease in blood
      pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 %
      decrease in infarct size, respectively. Replacing blood losses with crystalloid
      fluids (instead of blood) during surgery also reduced infarct size. To our
      knowledge, this is the largest analysis of the determinants of infarct size in
      mice ever published. The results demonstrate that genetic background, gender, age
      (but not in ICR), body temperature and arterial blood pH have a major impact on
      infarct size, and thus need to be carefully measured and/or taken into account
      when designing a study of myocardial infarction in mice; failure to do so makes
      results uninterpretable. For example, core temperature and blood pH need to be
      measured, respiratory acidosis (or alkalosis) and hypothermia (or hyperthermia)
      must be avoided, and comparisons cannot be made between mouse strains or genders
      that exhibit different susceptibility to I/R injury (e.g., FVB/N male mice and
      ICR female mice are inherently protected against I/R injury).

PMID- 22864683
TI  - Expression of VAV1 in the tumour microenvironment of glioblastoma multiforme.
AB  - Even though much progress has been made towards understanding the molecular
      nature of glioma, the survival rates of patients affected by this tumour have not
      changed significantly over recent years. Better knowledge of this malignancy is
      still needed in order to predict its outcome and improve patient treatment. VAV1
      is an GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that
      is involved in the regulation of cytoskeletal dynamics and cell migration. Here
      we report its overexpression in 59 patients diagnosed with high-grade glioma, and
      the associated upregulation of a number of genes coding for proteins also
      involved in cell invasion- and migration-related processes. Unexpectedly,
      immunohistochemical experiments revealed that VAV1 is not expressed in glioma
      cells. Instead, VAV1 is found in non-tumoural astrocyte-like cells that are
      located either peritumouraly or perivascularly. We propose that the expression of
      VAV1 is linked to synergistic signalling cross-talk between cancer and
      infiltrating cells. Interestingly, we show that the pattern of expression of VAV1
      could have a role in the neoplastic process in glioblastoma tumours.

PMID- 22864684
TI  - The use of sterilized mosquito nets for hernioplasty: a systematic review.
AB  - INTRODUCTION: Hernia repair is among the most frequent surgeries performed.
      Surgeons prefer the tension-free mesh repair, but in large parts of the world,
      commercial meshes are unavailable or unaffordable. Consequently, surgeons have
      been experimenting with insertion of inexpensive non-commercial meshes, the most
      common being a non-impregnated, sterilized mosquito net. OBJECTIVE: To describe
      the results of inserting non-commercial meshes for hernioplastic surgery.
      METHODS: Systematic searches were performed in EMBASE, PubMed, and Cochrane
      databases, and articles were chosen based on predefined inclusion criteria.
      RESULTS: We found five original studies performed in humans, and one study was
      performed in goats using non-commercial meshes. A total of 577 non-commercial
      meshes have been inserted into humans, resulting in 35 patients (6.1 %) having
      short-term complications and one (0.17 %) recurrence. The majority of meshes
      inserted were mosquito nets. None of the short-term complications in any of the
      studies required reoperation. CONCLUSIONS: There seems to be good short-term and
      long-term outcomes when using non-commercial meshes for open inguinal hernia
      repair. Operating using a non-commercial mesh is highly cost-effective. Using non
      commercial meshes for hernioplastic surgery is therefore interesting-especially
      in a resource-limited setting.

PMID- 22864685
TI  - CD99 expression and newly diagnosed diffuse large B-cell lymphoma treated with
      rituximab-CHOP immunochemotherapy.
AB  - In order to evaluate prognostic value of CD99 expression in patients with diffuse
      large B-cell lymphoma (DLBCL) who underwent treatment with rituximab-CHOP
      immunochemotherapy, immunohistochemistry for CD99/CD10/BCL-2/BCL-6/MUM-1 was
      performed on nodal DLBCL specimens from 70 patients. Patients were classified as
      either germinal center B-cell (GCB) subtype or non-GCB subtype according to the
      Muris algorithm. A superior 2-year event-free survival (EFS) was observed in
      patients with the GCB subgroup, compared to those with the non-GCB subgroup (p =
      0.034). The distribution of CD99 expression (29 patients; 41.4 %) did not show
      deviation according to subtype and was not prognostic for survival in the entire
      patient population. Among patients with the GCB subgroup, better EFS and overall
      survival (OS) were observed in CD99+ patients, compared to CD99- patients.
      Conversely, among patients with the non-GCB subgroup, inferior EFS and OS were
      reported in CD99+ patients. Superior 2-year EFS (p = 0.004) and 2-year OS (p =
      0.003) were observed in patients with GCB/CD99+ and non-GCB/CD99- compared to the
      others, and the combination classification was found to be an independent
      prognostic factor.

PMID- 22864687
TI  - Imaging equipment manufacturers' websites: information at your fingertips?

PMID- 22864686
TI  - The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via
      induction of tumor suppressor PTEN: similarities and distinct actions from soy
      isoflavone genistein.
AB  - Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle
      are major contributing factors to increased breast cancer risk. While mechanisms
      underlying dietary protection of mammary tumor formation are increasingly
      elucidated, there remains a dearth of knowledge on the nature and precise actions
      of specific bioactive components present in foods with purported health effects.
      The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable
      similar to the isoflavone genistein (GEN), and thus may mediate the beneficial
      effects of soy food consumption. Here, we evaluated whether LUN displays common
      and distinct actions from those of GEN in non-malignant (mouse HC11) and
      malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up
      regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome
      ten (PTEN) promoter activity, increased PTEN transcript and protein levels and
      enhanced nuclear PTEN localization, similar to that shown for GEN in mammary
      epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by
      PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and
      beta-catenin non-nuclear localization similar to GEN, but unlike GEN, did not
      influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN
      did not recapitulate GEN inhibitory effects on expansion of the cancer stem
      like/progenitor population in MCF-7 cells. Results suggest the concerted actions
      of GEN and LUN on cellular apoptosis for potential mammary tumor preventive
      effects and highlight whole food consumption rather than intake of specific
      dietary supplements with limited biological effects for greater health benefits.

PMID- 22864688
TI  - The effect of titanium amendment in N-withholding nutrient solution on
      physiological and photosynthesis attributes and micronutrient uptake of tomato.
AB  - Titanium (Ti) is a beneficial element that promotes growth and biomass production
      although the mechanism by which this improvement takes place is still unclear, as
      are other effects on plants, although it is believed that Ti can compensate for N
      deficiency. To prove this hypothesis, a hydroponic experiment was designed to
      investigate the effect of adding Ti to a nutrient solution on the nutrient uptake
      of tomato (Lycopersicon esculentum L.) by withholding N within the nutrient
      solution (NS) by 25 % (NS2) and by 50 % (NS1). Ti was added at 1 and 2 mg L-1.
      When Ti was added to nutrient solution, the elemental concentration in tomato
      changed significantly: K, Ca, Fe, and Zn decreased while Ti increased. As the
      concentration of N in nutrient solution decreased, the Ca and Ti concentration of
      tomato leaves decreased and the K, Mn, Fe, Cu, and Zn concentration increased. As
      the N concentration in nutrient solution increased, the Ca concentration
      decreased although the application of Ti compensated for Ca concentration in NS1.
      All the photosynthetic attributes and physiological characteristics, including
      flower induction, decreased when the N concentration of NS decreased by 50 %,
      although this decrease could be compensated by applying 1 mg L-1 Ti. This has
      valuable and practical applications and implications for tomato hydroponic
      culture.

PMID- 22864691
TI  - The man, the myth, the legend: Professor Terry V. Callaghan and his 3M concept.

PMID- 22864690
TI  - Measurement of dyspnea in patients with obstructive sleep apnea.
AB  - PURPOSE: Patients with obstructive sleep apnea (OSA) frequently complain of
      exertional dyspnea. We aimed to assess its related factors and the significance
      of its measurement in OSA. METHODS: We evaluated 301 subjects with suspected OSA
      for dyspnea during activities of daily living using the Medical Research Council
      (MRC) scale. We analyzed the relationships between MRC grades and various
      subjective and objective indices. Further, the relationship of disease severity
      based on the apnea/hypopnea index (AHI) with these indices was examined. Results
      were compared between those obtained using MRC grades and the AHI. RESULTS: Of
      301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in
      non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC
      grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various
      measurements differed significantly between groups categorized according to the
      MRC scale although determinants between mild and moderate groups and between
      moderate and severe groups differed. AHI categorizations were not significantly
      related to patient-reported measurements such as the Medical Outcomes Study 36
      item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and
      Depression Scale scores, unlike categorization based on the MRC scale.
      CONCLUSIONS: Dyspnea is an important outcome in OSA although dyspnea in OSA
      patients is unrelated to the sleep disorder per se. Measurement of dyspnea in
      patients with OSA might provide further insights into the health of these
      patients and clinical manifestations of this disease.

PMID- 22864692
TI  - Environmental monitoring and research in the Abisko area-an overview.
AB  - This article gives an overview of the studies on the environment surrounding the
      Abisko Scientific Research Station in Swedish Lapland. The long-term monitoring
      of the Station on processes related to the climate, and to the physical, biotic,
      and chemical environmental conditions is particularly addressed. Some variables
      are recorded since more than 100 years. The obtained data in combination with
      results from short-term studies and manipulation experiments are important to
      understand past and future conditions of the ecosystems. This has practical
      applications for the planning of tourism, transports, reindeer herding, and for
      societal purposes.

PMID- 22864693
TI  - Changes versus homeostasis in alpine and sub-alpine vegetation over three decades
      in the sub-arctic.
AB  - Plant species distributions are expected to shift and diversity is expected to
      decline as a result of global climate change, particularly in the Arctic where
      climate warming is amplified. We have recorded the changes in richness and
      abundance of vascular plants at Abisko, sub-Arctic Sweden, by re-sampling five
      studies consisting of seven datasets; one in the mountain birch forest and six at
      open sites. The oldest study was initiated in 1977-1979 and the latest in 1992.
      Total species number increased at all sites except for the birch forest site
      where richness decreased. We found no general pattern in how composition of
      vascular plants has changed over time. Three species, Calamagrostis lapponica,
      Carex vaginata and Salix reticulata, showed an overall increase in
      cover/frequency, while two Equisetum taxa decreased. Instead, we showed that the
      magnitude and direction of changes in species richness and composition differ
      among sites.

PMID- 22864694
TI  - Treelines will be understood once the functional difference between a tree and a
      shrub is.
AB  - Trees are taller than shrubs, grasses, and herbs. What is the disadvantage of
      being tall so that trees are restricted to warmer regions than low stature life
      forms? This article offers a brief review of the current state of biological
      treeline theory, and then explores the significance of tallness from a carbon
      balance, freezing resistance, and microclimatological perspective. It will be
      argued that having of a woody stem is neither a burden to the carbon balance nor
      does it add to the risk of freezing damage. The physiological means of trees to
      thrive in cold climates are similar to small stature plants, but due to their
      size, and, thus, closer aerodynamic coupling to air circulation, trees experience
      critically low temperatures at lower elevation and latitude than smaller plants.
      Hence, trees reach a limit at treeline for physical reasons related to their
      stature.

PMID- 22864695
TI  - Monitoring the multi-year carbon balance of a subarctic palsa mire with
      micrometeorological techniques.
AB  - This article reports a dataset on 8 years of monitoring carbon fluxes in a
      subarctic palsa mire based on micrometeorological eddy covariance measurements.
      The mire is a complex with wet minerotrophic areas and elevated dry palsa as well
      as intermediate sub-ecosystems. The measurements document primarily the emission
      originating from the wet parts of the mire dominated by a rather homogenous cover
      of Eriophorum angustifolium. The CO(2)/CH(4) flux measurements performed during
      the years 2001-2008 showed that the areas represented in the measurements were a
      relatively stable sink of carbon with an average annual rate of uptake amounting
      to on average -46 g C m(-2) y(-1) including an equally stable loss through CH(4)
      emissions (18-22 g CH(4)-C m(-2) y(-1)). This consistent carbon sink combined
      with substantial CH(4) emissions is most likely what is to be expected as the
      permafrost under palsa mires degrades in response to climate warming.

PMID- 22864696
TI  - Two decades of experimental manipulations of heaths and forest understory in the
      subarctic.
AB  - Current atmospheric warming due to increase of greenhouse gases will have severe
      consequences for the structure and functioning of arctic ecosystems with changes
      that, in turn, may feed back on the global-scale composition of the atmosphere.
      During more than two decades, environmental controls on biological and
      biogeochemical processes and possible atmospheric feedbacks have been intensely
      investigated at Abisko, Sweden, by long-term ecosystem manipulations. The
      research has addressed questions like environmental regulation of plant and
      microbial community structure and biomass, carbon and nutrient pools and element
      cycling, including exchange of greenhouse gases and volatile organic compounds,
      with focus on fundamental processes in the interface between plants, soil and
      root-associated and free-living soil microorganisms. The ultimate goal has been
      to infer from these multi-decadal experiments how subarctic and arctic ecosystems
      will respond to likely environmental changes in the future. Here we give an
      overview of some of the experiments and main results.

PMID- 22864697
TI  - Controls on coarse wood decay in temperate tree species: birth of the LOGLIFE
      experiment.
AB  - Dead wood provides a huge terrestrial carbon stock and a habitat to wide-ranging
      organisms during its decay. Our brief review highlights that, in order to
      understand environmental change impacts on these functions, we need to quantify
      the contributions of different interacting biotic and abiotic drivers to wood
      decomposition. LOGLIFE is a new long-term 'common-garden' experiment to
      disentangle the effects of species' wood traits and site-related environmental
      drivers on wood decomposition dynamics and its associated diversity of microbial
      and invertebrate communities. This experiment is firmly rooted in pioneering
      experiments under the directorship of Terry Callaghan at Abisko Research Station,
      Sweden. LOGLIFE features two contrasting forest sites in the Netherlands, each
      hosting a similar set of coarse logs and branches of 10 tree species. LOGLIFE
      welcomes other researchers to test further questions concerning coarse wood decay
      that will also help to optimise forest management in view of carbon sequestration
      and biodiversity conservation.

PMID- 22864698
TI  - Ecosystem response to climatic change: the importance of the cold season.
AB  - Winter climate and snow cover are the important drivers of plant community
      development in polar regions. However, the impacts of changing winter climate and
      associated changes in snow regime have received much less attention than changes
      during summer. Here, we synthesize the results from studies on the impacts of
      extreme winter weather events on polar heathland and lichen communities. Dwarf
      shrubs, mosses and soil arthropods were negatively impacted by extreme warming
      events while lichens showed variable responses to changes in extreme winter
      weather events. Snow mould formation underneath the snow may contribute to
      spatial heterogeneity in plant growth, arthropod communities and carbon cycling.
      Winter snow cover and depth will drive the reported impacts of winter climate
      change and add to spatial patterns in vegetation heterogeneity. The challenges
      ahead lie in obtaining better predictions on the snow patterns across the
      landscape and how these will be altered due to winter climate change.

PMID- 22864699
TI  - Enhanced UV-B and elevated CO(2) impacts sub-arctic shrub berry abundance,
      quality and seed germination.
AB  - This study investigated the effects of long-term-enhanced UV-B, and combined UV-B
      with elevated CO(2) on dwarf shrub berry characteristics in a sub-arctic heath
      community. Germination of Vaccinium myrtillus was enhanced in seeds produced at
      elevated UV-B, but seed numbers and berry size were unaffected. Elevated UV-B and
      CO(2) stimulated the abundance of V. myrtillus berries, whilst UV-B alone
      stimulated the berry abundance of V. vitis-idaea and Empetrum hermaphroditum.
      Enhanced UV-B reduced concentrations of several polyphenolics in V. myrtillus
      berries, whilst elevated CO(2) increased quercetin glycosides in V. myrtillus,
      and syringetin glycosides and anthocyanins in E. hermaphroditum berries. UV-B *
      CO(2) interactions were found for total anthocyanins, delphinidin-3-hexoside and
      peonidin-3-pentosidein in V. myrtillus berries but not E. hermaphroditum. Results
      suggest positive impacts of UV-B on the germination of V. myrtillus and species
      specific impacts of UV-B * elevated CO(2) on berry abundance and quality. The
      findings have relevance and implications for human and animal consumers plus seed
      dispersal and seedling establishment.

PMID- 22864700
TI  - Tundra in the rain: differential vegetation responses to three years of
      experimentally doubled summer precipitation in Siberian shrub and Swedish bog
      tundra.
AB  - Precipitation amounts and patterns at high latitude sites have been predicted to
      change as a result of global climatic changes. We addressed vegetation responses
      to three years of experimentally increased summer precipitation in two previously
      unaddressed tundra types: Betula nana-dominated shrub tundra (northeast Siberia)
      and a dry Sphagnum fuscum-dominated bog (northern Sweden). Positive responses to
      approximately doubled ambient precipitation (an increase of 200 mm year(-1)) were
      observed at the Siberian site, for B. nana (30 % larger length increments), Salix
      pulchra (leaf size and length increments) and Arctagrostis latifolia (leaf size
      and specific leaf area), but none were observed at the Swedish site. Total
      biomass production did not increase at either of the study sites. This study
      corroborates studies in other tundra vegetation types and shows that despite
      regional differences at the plant level, total tundra plant productivity is, at
      least at the short or medium term, largely irresponsive to experimentally
      increased summer precipitation.

PMID- 22864701
TI  - Modelling tundra vegetation response to recent arctic warming.
AB  - The Arctic land area has warmed by > 1  degrees C in the last 30 years and there
      is evidence that this has led to increased productivity and stature of tundra
      vegetation and reduced albedo, effecting a positive (amplifying) feedback to
      climate warming. We applied an individual-based dynamic vegetation model over the
      Arctic forced by observed climate and atmospheric CO(2) for 1980-2006. Averaged
      over the study area, the model simulated increases in primary production and leaf
      area index, and an increasing representation of shrubs and trees in vegetation.
      The main underlying mechanism was a warming-driven increase in growing season
      length, enhancing the production of shrubs and trees to the detriment of shaded
      ground-level vegetation. The simulated vegetation changes were estimated to
      correspond to a 1.75 % decline in snow-season albedo. Implications for modelling
      future climate impacts on Arctic ecosystems and for the incorporation of
      biogeophysical feedback mechanisms in Arctic system models are discussed.

PMID- 22864702
TI  - Linking fine-scale sub-arctic vegetation distribution in complex topography with
      surface-air-temperature modelled at 50-m resolution.
AB  - Recent studies have shown that the complexities of the surface features in
      mountainous terrain require a re-assessment of climate impacts at the local
      level. We explored the importance of surface-air-temperature based on a recently
      published 50-m-gridded dataset, versus soil variables for explaining vegetation
      distribution in Swedish Lapland using generalised linear models (GLMs). The
      results demonstrated that the current distribution of the birch forest and
      snowbed community strongly relied on the surface-air-temperature. However,
      temperature alone is a poor predictor of many plant communities (wetland,
      meadow). Because of diminishing sample representation with increasing altitude,
      the snowbed community was under-sampled at higher altitudes. This results in
      underestimation of the current distribution of the snowbed community around the
      mountain summits. The analysis suggests that caution is warranted when applying
      GLMs at the local level.

PMID- 22864703
TI  - Future distribution of Arctic char Salvelinus alpinus in Sweden under climate
      change: effects of temperature, lake size and species interactions.
AB  - Novel communities will be formed as species with a variety of dispersal abilities
      and environmental tolerances respond individually to climate change. Thus, models
      projecting future species distributions must account for species interactions and
      differential dispersal abilities. We developed a species distribution model for
      Arctic char Salvelinus alpinus, a freshwater fish that is sensitive both to warm
      temperatures and to species interactions. A logistic regression model using lake
      area, mean annual air temperature (1961-1990), pike Esox lucius and brown trout
      Salmo trutta occurrence correctly classified 95 % of 467 Swedish lakes. We
      predicted that Arctic char will lose 73 % of its range in Sweden by 2100.
      Predicted extinctions could be attributed both to simulated temperature increases
      and to projected pike invasions. The Swedish mountains will continue to provide
      refugia for Arctic char in the future and should be the focus of conservation
      efforts for this highly valued fish.

PMID- 22864704
TI  - Post scriptum: wider perspectives and the legacy.

PMID- 22864705
TI  - Carbon nanotube enhanced label-free immunosensor for amperometric determination
      of oocyte maturation-inducing hormone in fish.
AB  - Maintaining high-quality fish eggs stably and efficiently is important for
      aquaculture. We developed a label-free immunosensor system for measuring
      17,20beta-dihydroxy-4-pregnen-3-one (DHP). DHP is suddenly secreted before
      ovulation as a maturation-inducing hormone in fish, and therefore, DHP levels are
      an indicator for predicting ovulation. The method is based on immunologic
      reactions and amperometric measurement using cyclic voltammetry (CV). For
      biomolecular immobilization on the surface of sensing electrode, Au electrode, we
      used self-assembled monolayers of thiol-containing compounds to fix anti-DHP
      immunoglobulin. In addition, we used a single-walled carbon nanotube to improve
      sensitivity. Using this electrode, we were able to determine the CV signal change
      caused by the antigen-antibody complex. The proposed immunosensor system showed a
      linear correlation (correlation coefficient: 0.9827) between the anodic peak
      current of the CV and the DHP level in range from 15.6 to 50,000 pg ml(-1). The
      sensor system was then applied to monitor DHP of goldfish (Carassius auratus).
      Blood plasma of fish was collected every 3 h after administering a DHP inducer.
      In the measurement, the anodic peak current of the CV showed distinct changes
      depending on DHP levels in the blood plasma. A good relationship was observed
      between DHP levels determined by our proposed system and the conventional method
      (correlation coefficient: 0.9351).

PMID- 22864706
TI  - Molecular cloning, characterization, and gene expression of the androgen receptor
      in the large yellow croaker, Larimichthys crocea.
AB  - Androgens mediate a wide range of physiological responses and developmental
      processes in vertebrates, involving both reproductive and nonreproductive
      systems. The activity of androgens is mediated by the androgen receptor (AR), a
      member of the nuclear receptor superfamily. In this study, an AR gene was cloned
      from the large yellow croaker (Larimichthys crocea) for the first time. qRT-PCR
      revealed ubiquitous expression of AR in all adult tissues examined, with higher
      expression in the gonad and liver of both sexes and highest expression in the
      blastula stage of embryonic development. Using in situ hybridization, we detected
      positive signals of AR in the spermatogonium, spermatocyte, spermatid, and
      spermatozoon during spermatogenesis, in the cytoplasm of all oocytes during
      oogenesis and in the follicle cells of stage IV oocytes. Our findings support the
      important role that AR plays in gametogenesis, gonadal development, and the early
      stages of embryonic development.

PMID- 22864709
TI  - Alpha-1 protease inhibitor and antichymotrypsin levels in acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis with high mortality of severe onset is still a
      major problem in medicine. Early identification of the severity of the disease is
      critical for effective treatment. Many markers have been tried and are still
      being tested. The ideal marker should be able to identify the cases and
      distinguish between mild and severe. METHODS: This prospective study included 34
      cases (14 males, 20 females, mean age: 58 years) of acute pancreatitis and 33
      cases (17 males, 16 females, mean age: 53 years) as a control group. Mild (n=29)
      and severe (n=5) cases were compared with respect to serum levels of amylase, C
      reactive protein (CRP), alpha-1-protease inhibitor, and antichymotrypsin on
      admission and 24 and 48 hours (h) after admission. RESULTS: Alpha-1 protease
      inhibitor and antichymotrypsin levels were significantly elevated in the first 24
      h; however, CRP peaked after 48 h in the acute pancreatitis group. While CRP
      showed significantly higher concentrations in patients with severe pancreatitis,
      alpha-1-protease inhibitor and antichymotrypsin levels changed slightly, but
      without significance, in severe cases. CONCLUSION: Alpha-1 protease inhibitor and
      antichymotrypsin are early events in acute pancreatitis, with high levels on
      admission. Activation of these variables declines after 24 h. These markers may
      have early diagnostic value in patients with acute pancreatitis. Because neither
      of them is good at discrimination of mild and severe cases in the disease, they
      should not be incorporated into routine clinical investigations.

PMID- 22864708
TI  - Arbuscular mycorrhizal fungal community differs between a coexisting native shrub
      and introduced annual grass.
AB  - Arbuscular mycorrhizal fungi (AMF) have been implicated in non-native plant
      invasion success and persistence. However, few studies have identified the AMF
      species associating directly with plant invaders, or how these associations
      differ from those of native plant species. Identifying changes to the AMF
      community due to plant invasion could yield key plant-AMF interactions necessary
      for the restoration of native plant communities. This research compared AMF
      associating with coexisting Bromus tectorum, an invasive annual grass, and
      Artemisia tridentata, the dominant native shrub in western North America. At
      three sites, soil and root samples from Bromus and Artemisia were collected.
      Sporulation was induced using trap cultures, and spores were identified using
      morphological characteristics. DNA was extracted from root and soil subsamples
      and amplified. Sequences obtained were aligned and analyzed to compare diversity,
      composition, and phylogenetic distance between hosts and sites. Richness of AMF
      species associated with Artemisia in cultures was higher than AMF species
      associated with Bromus. Gamma diversity was similar and beta diversity was higher
      in AMF associated with Bromus compared to Artemisia. AMF community composition
      differed between hosts in both cultures and roots. Two AMF species (Archaeospora
      trappei and Viscospora viscosum) associated more frequently with Artemisia than
      Bromus across multiple sites. AMF communities in Bromus roots were more
      phylogenetically dispersed than in Artemisia roots, indicating a greater
      competition for resources within the invasive grass. Bromus associated with an
      AMF community that differed from Artemisia in a number of ways, and these changes
      could restrict native plant establishment.

PMID- 22864710
TI  - Presence of accompanying head injury in patients with maxillofacial trauma.
AB  - BACKGROUND: Patients with maxillofacial fractures are at high risk of
      accompanying traumatic cranial injuries. Prompt determination of head injury in
      these patients is crucial for improving patient survival and recovery. METHODS:
      The records of 246 patients with maxillofacial fractures referred to the
      emergency department of our hospital between January 2006 and September 2009 were
      reviewed in this retrospective study. The patients' age and gender, cause, type
      and location of the maxillofacial fracture, and the cranial injuries were
      analyzed. RESULTS: The mean age of the patients was 23.61+/-16.75 years (83.3%
      males and 16.7% females). Cranial injury was observed in 38 patients with
      maxillofacial trauma. While the risk of head injury was found to be 3.44-fold
      lower among patients with single facial bone fracture (p<0.001), the risk of
      experiencing head injury significantly increased in patients with multiple facial
      bone fractures (p<0.001). The risk of head trauma significantly increased in
      patients with fractures of the nasal bone, maxillary bone, mandibular bone, and
      with frontal region fractures (p<0.05 in each group). CONCLUSION: The patients
      with multiple facial bone fractures should be investigated with regard to head
      injury even if they do not have clinical findings.

PMID- 22864711
TI  - Reconstruction of a distal extremity defect using a temporoparietal fascia flap
      covered with a split-thickness skin graft harvested from the scalp: a cosmetic
      consideration in donor site selection.
AB  - BACKGROUND: In reconstructive surgery, the ultimate goal in rebuilding a
      structure is to provide the most similar substitute from both the functional and
      structural points of view. At the same time, the reconstructive surgeon should
      focus on minimizing donor area complications. METHODS: In this report, we present
      our experiences with the reconstruction of distal extremity defects using a free
      temporoparietal fascia flap in five patients. The flap was subsequently covered
      with a split-thickness skin graft harvested from the same region of the scalp as
      the flap donor site. RESULTS: By procuring the skin graft from the scalp, the
      donor sites of both the flap and the skin graft were concealed by hair. The
      transferred flaps and skin grafts healed uneventfully in all patients without any
      complications at the donor or recipient site. CONCLUSION: We conclude that this
      combination of harvesting a temporoparietal fascia flap, which has many
      advantages in reconstructing distal extremity defects, along with a skin graft
      from the same region as the flap, both hidden by hair, can limit donor site
      morbidity and achieve optimal reconstructive outcomes.

PMID- 22864712
TI  - Epidemiology of head injury in the United Arab Emirates.
AB  - BACKGROUND: Head injury increases mortality in trauma patients. We aimed to study
      the epidemiological and clinical features of head injury in Al-Ain city, United
      Arab Emirates (UAE). METHODS: Trauma patients with head injury who were admitted
      to Al- Ain Hospital for more than 24 hours and those who died in the hospital
      were included in the study. Data were prospectively collected from March 2003 -
      March 2006. RESULTS: 589 patients were studied, and 521 were males (88.3%). The
      median (range) age was 30 (1-89) years. The most common mechanism of injury was
      road traffic collision (67.1%) followed by fall from height (11.9%). Head injury
      was mild in 82.2% of patients, moderate in 5.7%, and severe in 12.1%. 20.9% of
      patients were admitted to the intensive care unit. 35 patients died (overall
      mortality 5.9%). Patients who died had significantly higher Injury Severity Score
      (p<0.0001), lower Glasgow Coma Scale (p<0.0001), and higher Abbreviated Injury
      Scale of the head (p<0.0001). CONCLUSION: Motor vehicle collision was the main
      mechanism of head injury in the UAE followed by fall from height. Legislation for
      compulsory seatbelt usage and helmet usage by bicyclists and motorcyclists should
      be adopted. A safe work environment and preventive measures at work should be
      introduced.

PMID- 22864713
TI  - Determinants of mortality in patients with traumatic brain injury.
AB  - BACKGROUND: We aimed to determine factors associated with mortality rates in
      patients with traumatic brain injury (TBI). METHODS: Registered data of a
      national trauma project conducted in eight major cities in Iran during a five
      year period were used. Patients with a TBI were identified and both univariate
      and multivariate analyses were performed. RESULTS: 2274 brain-injured patients
      including 1794 males (78.9%) were identified. The mean age of the patients was
      30.1 +/- 19.11 years. The age of 345 patients was less than 12, while 137
      patients were older than 65. 383 patients (16.9%) died as a result of their
      injury. Univariate analysis showed a significant association between mortality
      and the following factors: age, sex, Glasgow Coma Scale (GCS), Injury Severity
      Score (ISS), systolic, diastolic and mean arterial blood pressure (BP), and
      respiratory rate (RR) (p<0.05).The logistic regression analysis revealed a
      statistically significant association between death and age (odds ratio
      [OR]=1.04), GCS (OR=0.59), ISS (OR=1.03), mean arterial BP (OR=0.71), and RR
      (OR=0.82) one-half hour after hospital arrival. CONCLUSION: Our results
      demonstrated that age, GCS, ISS, BP, and RR as prognostic factors in patients
      with TBI indicate those that need special care during the initial management in
      the emergency department.

PMID- 22864715
TI  - Effects of decompressive surgery in patients with severe traumatic brain injury
      and bilateral non-reactive dilated pupils.
AB  - BACKGROUND: We investigated Glasgow Coma Scale (GCS) scores, intracranial
      pressure (ICP) and cerebral perfusion pressure (CPP) changes, and long-term
      clinical outcomes in patients with severe traumatic brain injury (STBI)
      associated with bilateral non-reactive dilated pupils (BNDP) who underwent
      decompressive surgery (DS). METHODS: The study group consisted of 28 patients (11
      females, 17 males) with BNDP from among 147 patients who underwent DS due to STBI
      in our department. RESULTS: The mean GCS score was 4.96+/-1.20 at admission and 4
      preoperatively. Mean ICP in non-surviving patients after DS was higher (p<0.05).
      ICP decrease after DS was also higher in surviving patients than in non-surviving
      patients (p<0.05). The overall mortality rate was 61.02%. A GCS motor score >2 at
      admission was associated with lower mortality (p<0.05). Four of the surviving
      patients (14.28%) had a functional outcome (Glasgow Outcome Score: 4 and 5) at
      one year after hospital discharge. CONCLUSION: Outcome in patients with BNDP
      after STBI may not always be fatal or poor. Rapid DS may increase the chance of
      functional survival, especially in patients with admission GCS score of 6 or 7.

PMID- 22864714
TI  - Role of red blood cell scintigraphy for determining the localization of
      gastrointestinal bleeding.
AB  - BACKGROUND: We aimed to evaluate the role of Tc-99m labeled red blood cell (RBC)
      scintigraphy for determination of localization of gastrointestinal system (GIS)
      bleeding. METHODS: Fifty-seven cases (27 females, 30 males; mean age 43.9+/-24;
      range 1 to 91 years) who referred to our clinic between 1995-2010 were evaluated
      for determination of localization of GIS bleeding with RBC scintigraphy. Prior to
      scintigraphy, gastroscopy in 51, colonoscopy in 45, and angiography in 9 patients
      were performed. RESULTS: RBC scintigraphies were positive and negative in 31 and
      26 patients, respectively. Positive scintigraphic findings were obtained within
      the 1st hour of dynamic imaging in 19 patients, within the 1st-4th hour static
      images in 7, and within the 4th-24th hour images in 5 patients. Fourteen patients
      underwent surgical exploration. In 13 patients, the surgery confirmed the
      diagnosis by RBC scintigraphy (accuracy: 92.8%). Of 43 patients without surgical
      exploration, 12 had anemia due to iron deficiency and their scintigraphic
      evaluation were negative. Four patients died and in 27 patients, GIS bleeding
      ceased spontaneously or with conservative measures. CONCLUSION: Scintigraphy
      should be the primary tool for accurate diagnosis of patients with active GIS
      bleeding. Positive dynamic images obtained within the first hour of imaging may
      be more accurate for demonstrating bleeding localization and a good predictor of
      requirement of surgical exploration.

PMID- 22864716
TI  - Trauma in women of child-bearing age in a high-income developing country.
AB  - BACKGROUND: We aimed to study the distribution and causes of trauma in women of
      child-bearing age. METHODS: Data were collected from Al-Ain Hospital (United Arab
      Emirates-UAE) Trauma Registry. Females aged 16 to 45 years (child-bearing age)
      who were admitted with trauma between March 2003 and March 2006 were included in
      the study. RESULTS: Females represented 9% (n=171) of all trauma patients
      (n=1809) of the same age group, of which 29% were UAE nationals. The mean age for
      females was 30.5 years. Road traffic collision (RTC) was the main mechanism of
      injury (n=78, 46%). Burns were significantly higher in females than males
      (p=0.001). Cervical fractures were significantly higher in females (p=0.04),
      while lumbar fractures were significantly higher in males (p=0.03). In females,
      pelvic fractures were diagnosed in 6.4%, spinal fractures in 7%, and both
      injuries in 1.2%. Three females died (1.7%), and all were due to RTC. CONCLUSION:
      The majority of females involved in trauma were aged 20- 34 years. RTC is the
      main mechanism of injury and fatality. Female trauma is associated with a high
      incidence of pelvic fractures. A higher rate of cervical injuries was observed in
      females in contrast to lumbar injuries in males.

PMID- 22864717
TI  - A newly designed intramedullary nail with distal interlocking system for tibia
      fractures in adults - the clinical results.
AB  - BACKGROUND: The surgical treatment of fractures of the tibia includes reamed and
      unreamed options. Reamed nails have mechanical advantages but they significantly
      harm the endosteal circulation. Unreamed nails spare the endosteal circulation,
      but provide a less stable fixation. In both systems, immediate full weight
      bearing is not possible due to instability related to distal interlocking (DI).
      Further, DI is responsible for the majority of the fluoroscopy requirement and a
      significant loss of surgical time. In our study, we present the clinical results
      of a new intramedullary (IM) nail and system, which allows stable fixation with
      an unreamed technique that permits immediate full weight-bearing, with a minimum
      fluoroscopy requirement for DI. METHODS: Fifty tibia fractures (49 patients)
      operated using our new IM system between 2008 and 2010 were evaluated
      retrospectively. They were allowed full weight-bearing the day after surgery. The
      patients were followed at least 10 months postoperatively. RESULTS: Mean
      fluoroscopy time was 18 seconds (min: 10, max: 30) for DI. Mean union time was 9
      weeks (min: 6, max: 12). There was no neurovascular injury, deep infection,
      malunion, delayed union, or nonunion. CONCLUSION: We demonstrated that our newly
      developed IM nail and new DI system may be an option to solve the stability
      problems sourced from the DI screw. It also significantly decreases the
      requirement of fluoroscopy.

PMID- 22864718
TI  - Rectal injury during radical prostatectomy.
AB  - BACKGROUND: We evaluated the data of our patients who experienced rectal injury
      during radical prostatectomy (RP). METHODS: We analyzed the data for the 7
      patients (6 perineal, 1 retropubic) with iatrogenic rectal injury who were
      selected from 451 patients with RP (218 retropubic, 233 perineal) operated in our
      clinic between 2003 and 2011. RESULTS: The mean age of the 7 patients was 64.4
      years. Rectal injury occurred during prostatic apical dissection in 4 patients,
      during dissection of Denonvilliers fascia in 1 patient, during transection of the
      rectourethral muscles in 1 patient, and during dissection of the rectal region
      proximal to the anal sphincter in 1 patient. The mean size of the lesions was 2
      (1-4) cm. All of the rectal injuries were recognized during the operation, and
      double-layered sutures were used for the primary repair. None of the cases
      required colostomy procedure. No postoperative complications were encountered in
      6 of the patients; however, 1 patient underwent a second operation on the
      following day due to detachment at the injury site. None of the patients
      displayed urethrorectal fistula, urinary incontinence or urethral stricture.
      CONCLUSION: Primary repair with double-layered suturing is sufficient for the
      treatment of rectal injuries that occur during RP if they are recognized
      intraoperatively.

PMID- 22864719
TI  - Pellet gunfire injuries among agitated mobs in Kashmir.
AB  - BACKGROUND: Pellet gunfire injuries inflicted while controlling agitated mobs has
      been studied. METHODS: A total of 198 patients admitted to the Accident and
      Emergency Department with pellet gun injuries were studied in terms of anatomic
      site, severity and type of injury, treatment, and outcomes. RESULTS: 72.7% of
      patients were aged 16-25 years. The most common sites of injury were the
      extremities (47.9%), abdomen (36.3%) and chest (31.3%). 59.5% of patients were
      found to have minor injuries. Of the 80 patients admitted to the hospital for
      their injuries, 43 (53.7%) required an operative procedure. Six deaths (3.03%)
      were observed. CONCLUSION: While the pellet wound itself may seem trivial, if not
      appreciated for the potential for tissue disruption and injuries to the head,
      chest, and abdomen, there can be catastrophic results. Patients should be
      evaluated and managed in the same way as those sustaining bullet injuries.:

PMID- 22864720
TI  - [Evaluation of the patients in Van Training and Research Hospital following the
      2011 Van earthquake in Turkey].
AB  - BACKGROUND: On 23 October 2011, an earthquake occurred in the city of Van,
      Turkey. This earthquake was an enormous devastating disaster and caused mass
      casualties. The descriptive analysis presented here serves as a reference not
      only for the present injury profile but also for future disaster response.
      METHODS: This is a retrospective study based on the medical records of earthquake
      victims admitted to Van Training and Research Hospital. The results were compared
      with the current literature. RESULTS: 1582 earthquake victims (806 male, 776
      female, mean age 36.9 years) were admitted to emergency service. 301 of the
      patients were treated with hospital care in different departments: 84 (27.9%) in
      orthopedics surgery, 40 (13.2%) in general and pediatric surgery, 26 (9%) in
      thorax surgery, 34 (11%) in neurosurgery, 56 (19%) in internal medicine, 39 (13%)
      in the intensive care unit, and 22 (7%) in other departments. The total number of
      deceased was 60. CONCLUSION: To minimize mortality and morbidity after earthquake
      disaster, immediate and effective triage should be done, and after the patients
      are transported to the hospital, individualized treatment should be planned
      according to the patients' respective clinical features. Coherent collaboration
      between many departments is vital.

PMID- 22864721
TI  - Penetrating head trauma with four nails: an extremely rare case.
AB  - We present a rare case of self-inflicted penetrating head trauma by a 34-year-old
      male who hammered four nails into his own head; he had been diagnosed with
      schizophrenia seven years before. On the physical examination, four nails were
      observed in the hairy scalp that had been driven into the cranium in the right
      temporal and parietal areas of the head. No cerebrospinal fluid fistulas were
      present. On the neurological examination, no motor or sensory deficits were
      present. The Glasgow Coma Scale was 15. On direct skull X-ray and cranial
      computerized tomography (CT), the nails were seen to be approximately 10 cm long
      and extending in various directions. No injury was observed in the main
      vasculature on CT angiography. Under general anesthesia, two nails in the right
      temporal area were removed by extraction, and the other two nails in the right
      parietal area were removed through a mini craniotomy. In areas such as the
      temporal area where the bone is thin, nails can be removed by extraction.
      However, in areas like the parietal bone where the bone is thick, removal of the
      nails using this method may not always be possible.

PMID- 22864722
TI  - Closed total (pan-talar) dislocation of the talus with delayed presentation: a
      rare case report and review of the literature.
AB  - Major fractures and dislocation of the talus and peritalar joint are uncommon. We
      present here a very rare case of injury with delayed presentation of closed total
      talus dislocation with fractured medial malleolus and posterior talar tubercle
      fracture. This report analyzes previous reports in the literature and the
      proposed treatment.

PMID- 22864723
TI  - Pyloric atresia associated with epidermolysis bullosa: report of two cases and
      review of the literature.
AB  - The coexistence of pyloric atresia (PA) and epidermolysis bullosa (EB) is a rare
      but well-known surgical emergency in neonates. PA/EB is described by the
      association of atresia of the pylorus and bullous lesions on the skin. Ninety one
      cases have been reported in the literature to date. We present two new cases and
      evaluate the association of PA/ EB, its etiopathogenesis and the clinical
      properties. Case 1: A three-day-old female presented with nonbilious vomiting and
      bullous lesions 2-3 cm in diameter on the extremities. Abdominal X-ray showed a
      single air-fluid level in the left upper quadrant. At laparotomy, we found PA and
      performed a pyloro-pylorostomy. The patient died due to sepsis complication of EB
      two months after surgery. Case 2: A two-day-old male presented with severe dermal
      bullous lesions on the trunk, neck and extremities. His stomach was dilated and
      there was no gas distally. We found PA and performed gastroduodenostomy.
      Initially, he tolerated the feeding well, but he died due to severe sepsis on the
      postoperative 23rd day. Almost all neonates born with the PA/EB result in a fatal
      outcome in the first few years. The complications related to EB are usually the
      cause of death. Even after successful repair of PA, skin lesions lead to death
      due to infection.

PMID- 22864724
TI  - A patient who was burned in the operative field: a case report.
AB  - Operating room fires occur very rarely. Nevertheless, a disaster can complicate
      almost any kind of surgery. The majority of operating room fires result from the
      use of alcohol- based surgical preparation solutions, electro-surgical equipment,
      or flammable drapes in an oxygen-rich environment. We report a patient with an
      ovarian cyst and uterine myomas who suffered a flame burn while undergoing
      gynecological surgery.

PMID- 22864725
TI  - Isolated hemorrhagic contusion of an incidental meningioma.
AB  - The authors present an unusual case of isolated hemorrhagic contusion of an
      incidental meningioma showing radiological findings similar to those of a
      hemorrhagic cerebral contusion on computed tomography (CT) in a female patient
      who presented to our hospital for head trauma. This case has two characteristics.
      First, although the meningioma had a hemorrhagic contusion due to head trauma,
      most of the brain tissue was intact. Second, there was a possibility that the
      hemorrhagic contusion of the incidental meningioma on CT was misdiagnosed as a
      cerebral hemorrhagic contusion. In this case, we propose a possible mechanism to
      explain this rare phenomenon.

PMID- 22864726
TI  - Intestinal malrotation in an adult: case report.
AB  - Intestinal malrotation is a developmental anomaly of the midgut in which the
      normal fetal rotation of intestines around the superior mesenteric artery and
      their fixation in the peritoneal cavity fail. Rotational anomalies of the midgut
      are rare in adults. Operative intervention is required generally when they are
      symptomatic. While difficult to diagnose, prompt recognition and surgical
      treatment usually lead to a successful outcome. Intestinal malrotation is rarely
      asymptomatic and generally diagnosed incidentally in adults. In the present
      report, a case of incidental intestinal malrotation with clinical findings of
      small bowel obstruction is discussed with a literature review.

PMID- 22864727
TI  - [Transcatheter aortic valve replacement: when should it be used in aortic
      stenosis?].
AB  - 30% of patients with significant aortic stenosis are not considered for operative
      aortic valve replacement because of the high perioperative risk. An alternative
      catheter based option for these patients is the transcatheter aortic valve
      replacement (TAVI). In general, there are two approaches for TAVI: transfemoral
      and transapical. Transfemoral aortic valve replacement is performed by
      transcatheter replacement of an aortic valve via the femoral arteries.
      Transapical valve replacement is achieved by transcatheter implantation via the
      fifth intercostal space. The most common complications are vessel injuries,
      bleeding complications, new onset of AV-block, development of paravalvular
      insufficiency, acute kidney injury, stroke and TIA. The first long-term
      observations suggest positive results. First clinical trials in a high-risk
      population show a promising outcome. Therefore TAVI offers a reasonable therapy
      option for patients with high perioperative risk. Further long-term clinical
      trials are still pending.

PMID- 22864728
TI  - Can triggers be cumulative in inducing heart attack in soccer game spectators?
AB  - Emotional stress and excitement associated with watching soccer matches has been
      suggested to act as an external trigger for the onset of acute coronary
      syndromes. We report about a patient of Italian nationality who developed acute
      coronary syndrome while watching the European football championship match
      Switzerland vs. Turkey in 2008. Although greater emotional intensity was possibly
      involved while watching his country play two days earlier (Italy vs Netherlands),
      he developed no symptoms. Hence, this case throws some interesting light on what
      can be considered as an acute trigger by discussing the assumption of a
      cumulative effect regarding to the potential trigger two days before and in which
      way psychological stress may have influence on the onset of acute coronary
      syndromes.

PMID- 22864729
TI  - Tetradecanuclear polycarbonatolanthanoid clusters: diverse coordination modes of
      carbonate providing access to novel core geometries.
AB  - The synthesis of two high nuclearity lanthanoid clusters demonstrates the
      versatility of the carbonate anion as a robust cluster forming agent, potentially
      allowing for the formation of otherwise inaccessible core topologies. The
      complexes,
      [Gd(14)(CO(3))(13)(ccnm)(9)(OH)(H(2)O)(6)(phen)(13)(NO(3))](CO(3))(2.5).(phen)(0.
      ) (1) and
      [Dy(14)(CO(3))(13)(ccnm)(10)(OH)(H(2)O)(6)(phen)(13)](CO(3))(2.5).(phen)(0.5) (2)
      (ccnm = carbamoylcyanonitrosomethanide, phen = 1,10-phenanthroline), contain a
      [Ln(14)(CO(3))(13)(OH)] core in which the carbonate anions display four unique
      coordination modes. The complexes are chiral, and the ccnm ligands also display
      four unique coordination modes. Extensive intra- and intermolecular pi-pi
      stacking between phen ligands leads to the formation of 1D chains in the crystal
      structure. Both complexes display magnetic properties that are indicative of
      antiferromagnetic coupling, with complex displaying behaviour consistent with
      possible single molecule magnet properties.

PMID- 22864730
TI  - Risks, benefits, and therapeutic potential of hematopoietic stem cell
      transplantation for autoimmune diabetes.
AB  - Type 1 diabetes mellitus is a chronic disease that results from the autoimmune
      response against pancreatic insulin producing beta cells. Apart of several
      insulin regimens, since the decade of 80s various immunomodulatory regimens were
      tested aiming at blocking some steps of the autoimmune process against beta cell
      mass and at promoting beta cell preservation. In the last years, some independent
      research groups tried to cure type 1 diabetes with an "immunologic reset"
      provided by autologous hematopoietic stem cell transplantation in newly diagnosed
      patients, and the majority of patients became free form insulin with increasing
      levels of C-peptide along the time. In this review, we discuss the biology of
      hematopoietic stem cells and the possible advantages and disadvantages related to
      the high dose immunosuppression followed by autologous hematopoietic stem cell
      transplantation.

PMID- 22864731
TI  - Comparison of upper gastrointestinal contrast studies and pH/impedance tests for
      the diagnosis of childhood gastro-oesophageal reflux.
AB  - BACKGROUND: The upper gastrointestinal (UGI) contrast study is used in the
      assessment of children with gastro-oesophageal reflux (GOR) and for detection of
      structural anomalies. The pH study is more sensitive than the UGI study for the
      diagnosis of GOR. The pH study has been replaced by the pH/impedance test, which
      detects both acid and nonacid reflux. OBJECTIVE: To compare the UGI contrast
      study with the pH/impedance test for the diagnosis of GOR in children. MATERIALS
      AND METHODS: We retrospectively reviewed consecutive records of children
      investigated for GOR from October 2008 to February 2010, and compared the
      findings of UGI studies with those of pH/impedance tests. RESULTS: The UGI
      studies revealed GOR in 116 of 579 children (20%). Of the children undergoing a
      UGI study, 66 also underwent a pH/impedance test. Using the pH/impedance tests as
      the reference for GOR, UGI had a sensitivity of 42.8% and a negative predictive
      value of 24%. There was no significant correlation (P > 0.05) between the reflux
      index and the number of reflux episodes in the pH/impedance tests and height of
      reflux in the UGI study. There were low incidences of malrotation (0.9%), hiatus
      hernia (1%) and delayed gastric emptying (0.4%). CONCLUSION: The UGI study had
      low sensitivity for the diagnosis of GOR and low yield for the diagnosis of
      structural anomalies.

PMID- 22864732
TI  - Fimasartan, a novel angiotensin II receptor antagonist.
AB  - Fimasartan (Kanarb(r)), an angiotensin II receptor antagonist with selectivity
      for the AT1 receptor subtype, is a pyrimidinone-related heterocyclic compound
      that was developed by Boryung Pharm. Co., Ltd. Among numerous synthetic
      derivatives, fimasartan was chosen as a new drug candidate through in vitro and
      in vivo screening studies. Pharmadynamic-pharmacokinetic properties and safety
      profiles were determined in a series of nonclinical and clinical studies.
      Fimasartan is a new angiotensin receptor blocker, and the first new molecular
      entity acting on cardiovascular system approved by Korean Food and Drug
      Administration for the treatment of essential hypertension in September 2010.
      Further development process for combination therapy and overseas registration is
      currently ongoing.

PMID- 22864733
TI  - Metabolites from the mangrove-derived fungus Xylaria cubensis PSU-MA34.
AB  - Two new succinic acid derivatives, xylacinic acids A (1) and B (2), along with
      seven known compounds, including one succinic acid derivative (3), three mellein
      derivatives (4-6), cytochalasin D (7), 2-chloro-5-methoxy-3-methylcyclohexa-2,5
      diene-1,4-dione (8) and isosclerone (9), were isolated from the mangrove-derived
      fungus Xylaria cubensis PSU-MA34. Their structures were established by
      spectroscopic evidence. They were evaluated for cytotoxicity against KB cells and
      antibacterial activity against Staphylococcus aureus ATCC 25923 and methicillin
      resistant S. aureus.

PMID- 22864734
TI  - Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium
      ophioglossum.
AB  - Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n
      hexane subfraction of the MeOH extract of the whole plant of Heliotropium
      ophioglossum along with glycerol monopalmitate (3) and beta-sitosterol 3-O-beta
      D: -glucoside (4) reported for the first time from this species. Their structures
      were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy.
      Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme
      urease.

PMID- 22864735
TI  - Antibacterial compounds from Zanthoxylum rhetsa.
AB  - A new amide, zanthorhetsamide (1), along with nine known compounds (2-10) was
      isolated from the roots and stem barks of Zanthoxylum rhetsa. The structure was
      characterized by spectroscopic methods. In addition, the antibacterial activity
      of the isolates was evaluated. Dihydrochelerythrine (4) exhibited strong activity
      against methicillin-resistant Staphylococcus aureus SK1 and moderate activity
      against Escherichia coli TISTR 780 with MIC values of 8 and 16 MUg/mL,
      respectively.

PMID- 22864736
TI  - Synthesis and pharmacological evaluation of [(4-arylpiperazin-1-yl)-alkyl]
      carbamic acid ethyl ester derivatives as potential anxiolytic agents.
AB  - On the basis of our earlier studies, a series of N-{4-[4-(aryl) piperazin-1-yl]
      phenyl}-amine derivatives containing terminal carbamoyl fragment with alkyl
      spacer of different lengths (15-20) were synthesized as ligands, for 5
      hydroxytryptamine-1A (5-HT(1A)) receptor. Molecular modeling studies were
      undertaken to explain the influence of spacer length on ligands affinity towards
      5-HT(1A) receptor. Compound 19 showed all the specific interactions responsible
      for recognition. The protonated amine of the ligand forms an ionic hydrogen bond
      with the negatively charged Asp116 of transmembrane3 helix (TM3), while the
      carbamoyl moiety interacts with Asn386 and Tyr390 of TM7. The aryl group is
      involved in forming a CH-pi interaction with Phe362. The strong interaction of
      compound 19 with 5-HT(1A) receptor in docking studies was confirmed by radio
      ligand binding studies. Compound 19 showed high affinity for the receptor (Ki =
      0.018 nM). In vivo pharmacological testing of compound 19 (3 mg/kg body weight)
      showed increased open arm entries, as well as time spent in Elevated plus Maze
      test. Toxicological analysis also revealed no significant biochemical or
      morphological alterations in the vital organs of experimental animals.
      Furthermore our results suggest that these compounds share some pharmacological
      effects with established anxiolytics and might prove to be effective compounds
      for the treatment of anxiety.

PMID- 22864737
TI  - Sesquiterpenoids from Farfugium japonicum and their inhibitory activity on NO
      production in RAW264.7 cells.
AB  - A new eremophilane sesquiterpenoid, namely, 3beta-angeloyloxy-6beta,8beta
      dihydroxy-9beta-senecioyloxyeremophil-7(11)-en-12,8alpha-lactone, along with
      eight known sesquiterpenoids, was isolated from the rhizome of Farfugium
      japonicum. The structures of all isolates were identified based on analyses of
      spectroscopic data (HRESIMS, IR, 1D, and 2D NMR) and comparison with literature
      data. The inhibitory effects of compounds 1-4 on nitric oxide production in
      lipopolysaccaride-activated mouse macrophages were also evaluated.

PMID- 22864738
TI  - The synthesis and characterization of fatty acid salts of chitosan as novel
      matrices for prolonged intragastric drug delivery.
AB  - The aim of this study was to prepare fatty acid salts of chitosan (CS) and to
      evaluate the salts as matrices for sustained drug release and prolonged gastric
      retention. CS-laurate and CS-palmitate were formed by mixing saturated CS
      solution and aqueous solutions of sodium laurate and sodium palmitate,
      respectively, and collected by centrifugation. They were characterized using
      Fourier-transform infrared spectroscopy and differential scanning calorimetry.
      Different matrices as effervescent tablets were prepared using each of these CS
      salts, CS and the corresponding physical mixtures of CS and the fatty acids.
      Sodium bicarbonate as an effervescent agent and ranitidine HCl as a model drug
      were incorporated into these matrices. In vitro buoyancy and drug dissolution
      were studied for the matrices in 0.1 M HCl. Tablets with fatty acid salts of CS
      showed both rapid and prolonged buoyancy (> 8 h). Comparatively, CS tablets
      exhibited a short floatation period (< 2 h) and tablets were completely
      disintegrated within 1 h of soaking. In addition, slow and prolonged drug release
      was achieved from tablets of fatty acid salts of CS with average drug release of
      80.1 and 71.8% for CS-laurate and CS-palmitate, respectively. Rapid drug release
      (> 80% at 1 h) was exhibited by tablets with CS or the physical mixtures.

PMID- 22864739
TI  - Inclusion complex effect on the bioavailability of clotrimazole from poloxamer
      based solid suppository.
AB  - To study the effect of beta-cyclodextrin (betaCD) inclusion complex on the
      bioavailability of clotrimazole from poloxamer-based suppository, formulations
      composed of P 188, propylene glycol and different molar ratio of clotrimazole
      betaCD inclusion complex were prepared. Clotrimazole (1%) has been formulated in
      a suppository using the thermo sensitive polymer P188 (70%) together with
      propylene glycol (30%). To increase its aqueous solubility, clotrimazole was
      incorporated as its inclusion complex at various molar ratios with betaCD
      (1:0.25, 1:0.5, 1:1, and 1:2). The inclusion complex was characterized by
      differential scanning calorimetry (DSC), XRD and phase solubility studies. It was
      observed that the complexation with betaCD, particularly at high molar ratio (F3
      (1:1) and F4 (1:2)) decreased the release profile of clotrimazole considerably.
      However, suppositories containing inclusion complex at low molar ratio (F1
      (1:0.25) and F2 (1:0.5)) showed excellent release profile compared to control
      formulation. In vivo study in rats at 15 mg/Kg dose showed that the F1 and F2
      (82.39 +/- 15.40 and 67.05 +/- 8.79, respectively) significantly increased the
      AUC compared to that of F3 (41.48 +/- 11.51), F4 (23.34 +/- 8.37) and control
      (46.7 +/- 7.87) suppositories. Thus, the suppositories containing inclusion
      complexes prepared at low drug to betaCD molar ratio (F1) could be a potential
      suppository formulation to increase the bioavailability of hydrophobic drugs such
      as clotrimazole.

PMID- 22864740
TI  - Physicochemical characterization and an injection formulation study of water
      insoluble ZCVI4-2, a novel NO-donor anticancer compound.
AB  - ZCVI(4)-2 was a novel nitric oxide-releasing glycosyl derivative of oleanolic
      acid that displayed strong cytotoxicity selectively against human hepatocellular
      carcinoma in vitro and in vivo. In this study, ZCVI(4)-2 was characterized by FT
      IR spectroscopy, differential scanning calorimetry, powder X-ray diffractometry,
      Raman spectroscopy, hygroscopicity and stability. A high performance liquid
      chromatography method was also established for the quantitative determination of
      solubility and additional stability profile of ZCVI(4)-2. ZCVI(4)-2 was found to
      be an amorphous and stable solid with low solubility of less than 10 MUg/mL.
      Based on the solubilization tests that included methods of cosolvency and
      micellization, the solution mixture of 5% Solutol HS-15, 5% 1, 2-propylene glycol
      and 5% anhydrous ethanol was determined to be the system for the preparation of
      the ZCVI(4)-2 early injection solution. The effect of pH, temperature, light and
      injectable isotonic glucose or NaCl solution on ZCVI(4)-2 injection was also
      investigated. Good stability was observed at all testing conditions. Under the
      conditions studied, the NO-releasing rate and amount of ZCVI(4)-2 from the early
      injection solution in rat plasma demonstrated a promising therapeutic efficacy
      while maintaining a good safety profile.

PMID- 22864741
TI  - Effect of particle size on the dissolution behaviors of poorly water-soluble
      drugs.
AB  - This study examined the effects of the particle size of various poorly water
      soluble drugs on their dissolution behavior through physicochemical and
      mathematical analysis. As model drugs, hydrochlorothiazide, aceclofenac,
      ibuprofen and a discovery candidate were selected. The materials were
      crystallized using an evaporation method and milled without transformation
      behavior of crystal forms. The particles were sieved and divided into four size
      groups (< 45 MUm, 45~150 MUm, 150~250 MUm, and 250~600 MUm). The specific surface
      area with regard to the particle size was measured using a BET surface area
      measurement. The specific surface area increased with decreasing particle size of
      the drug, resulting in an increase in dissolution rate. During the initial period
      of the dissolution study, significant differences in dissolution rate were
      observed according to the particle size and specific surface areas. On the other
      hand, in the later stages, the surface-specific dissolution rate was almost
      consistent regardless of the particle size. These observations were evaluated
      mathematically and the results suggested that the dissolution rate of poorly
      soluble drugs is strongly related to the particle size distribution. Moreover,
      physicochemical analysis helped explain the effect of particle size on the
      dissolution profiles.

PMID- 22864742
TI  - Development of prilocaine gels for enhanced local anesthetic action.
AB  - Prilocaine, one of local anesthetics, has been used for regional pain relief.
      When applied as an ointments or creams, it is hard to expect their effects to
      last for long time, because they are easily removed by wetting, movement and
      contacting. For more comfortable and better application, we developed a
      prilocaine gel system using a bioadhesive polymer, carboxymethyl cellulose (CMC).
      For suitable bioadhesion, the bioadhesive force of various polymers was tested
      using an auto-peeling tester. The bioadhesive force of various types of CMC such
      as 100MC, 150MC and 300MC, was 0.0264, 0.0461 and 0.0824 N, at 1.5%
      concentration, respectively. The CMC-300MC gels showed the most suitable
      bioadhesive forces. The effect of drug concentration on drug release was studied
      from the prepared 1.5% CMC gels using a synthetic cellulose membrane at 37 +/-
      0.5 degrees C. As the concentration of drug increased, the drug release
      increased. The effects of temperature on drug release from the 1.0% prilocaine
      gels were evaluated at 27, 32, 37 and 42 degrees C. As the temperature of the
      drug gels increased, drug release increased. The enhancing effects of penetration
      enhancers such as pyrrolidones, non-ionic surfactants, fatty acids and propylene
      glycol derivatives were studied. Among the enhancers used, polyoxyethylene 2
      oleyl ether was superior. The anesthetic effects were studied by a tail flick
      analgesic meter. In the rat tailflick test, 1.0% prilocaine gels containing
      polyoxyethylene 2-oleyl ether showed the most prolonged local analgesic effects.
      The results support the view that prilocaine gels with enhanced local anesthetic
      action could be developed using CMC bioadhesive polymer.

PMID- 22864743
TI  - Formulation parameters influencing the physicochemical characteristics of
      rosiglitazone-loaded cationic lipid emulsion.
AB  - To enhance the solubility of rosiglitazone, rosiglitazone-loaded cationic lipid
      emulsion was formulated using cationic lipid DOTAP, DOPE, castor oil, tween 20,
      and tween 80. The formulation parameters in terms of droplet size were optimized
      focused on the effect of the cationic lipid emulsion composition ratio on drug
      encapsulating efficiency, in vitro drug release, and cellular uptake of the
      rosiglitazone-loaded emulsion. Droplet sizes of a blank cationic emulsion and a
      rosiglitazone-loaded cationic emulsion ranged between 195-230 nm and 210-290 nm,
      respectively. The encapsulation efficiency of the rosiglitazone-loaded emulsion
      was more than 90%. The rosiglitazone-loaded cationic emulsion improved in vitro
      drug release over the drug alone and showed a much higher cellular uptake than
      rosiglitazone alone. Moreover, drug loading in cationic emulsions increased
      cellular uptake of rosiglitazone in insulin-resistant HepG2 cells more than the
      normal HepG2 cells. Taken together, these results indicate that cationic lipid
      emulsions could be a potential delivery system for rosiglitazone and could
      enhance its cellular uptake efficiency into target cells.

PMID- 22864744
TI  - Functional impairment of P-glycoprotein by sodium nitroprusside pretreatment in
      mouse brain capillary endothelial cells.
AB  - We examined whether pretreatment of mouse brain blood vessel endothelial cell
      clone 4 (MBEC4) cells with sodium nitroprusside (SNP), a NO(x) donor, as an in
      vitro model of the bloodbrain barrier could affect P-glycoprotein (P-gp)
      functional activity. Uptake into the cells and MBEC4 plasma membrane vesicles
      (MPMVs) in the presence or absence of SNP pretreatment was used to investigate
      functional changes. Increased accumulation of [(3)H]vincristine, a widely used
      substrate for P-gp, into MBEC4 was observed upon SNP pretreatment, likely due to
      impaired P-gp function. To better understand the mechanism of the impairment,
      MPMVs were prepared and characterized in terms of purity and Na(+)-dependent
      glucose uptake. [(3)H]daunomycin uptake into MPMVs was diminished after SNP
      pretreatment in the presence of an ATP-regenerating system, indicating that the
      functional activity of P-gp was impaired after exposure to SNP. Under conditions
      of excess ATP, daunomycin uptake into the vesicles was still decreased after SNP
      pretreatment, indicating that SNP interacted directly with the transport system,
      but not with the ATP-regenerating system. Together, these results suggest that NO
      or NO(x) functionally impairs P-gp in the in vitro blood-brain barrier model with
      SNP pretreatment.

PMID- 22864745
TI  - Effects of solvents and crystallization conditions on the polymorphic behaviors
      and dissolution rates of valsartan.
AB  - For the quality evaluation of raw materials, the influence of various types of
      solvents on the polymorphic crystallization behaviors and dissolution rates of
      two sources of valsartan (VAL) from China and India was investigated. Samples
      were prepared by recrystallization from water or organic solvents, such as
      acetonitrile, acetone and ethanol, using methods with and without heating.
      Recrystallization behaviors were characterized by differential scanning
      calorimetry (DSC) and powder X-ray diffraction (PXRD). Scanning electron
      microscopy (SEM) was also used to observe the morphology of samples. The
      dissolution rate of recrystallized samples in water was evaluated and compared to
      the original VAL sample. There were significant differences in morphology,
      crystal structure and dissolution rate among the samples recrystallized using
      organic solvents. VAL was transformed into another polymorphic form by the
      solvents and recrystallization conditions. These physical properties of VAL also
      differed between the two sources of VAL. Thus, the physicochemical differences of
      raw materials should be carefully considered in early dosage formulation
      approaches.

PMID- 22864746
TI  - Therapeutic effect of ginsenoside Rd in rats with TNBS-induced recurrent
      ulcerative colitis.
AB  - Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress and
      neutrophil infiltration. In the present study, we aimed to investigate the
      therapeutic effect of ginsenoside Rd (GRd) in rats with 2,4,6
      trinitrobenzenesulfonic acid (TNBS)-induced recurrent UC. After UC was twice
      induced by intracolonic injection of TNBS, rats were intragastrically
      administered different doses of GRd per day for 7 days. The colonic lesions and
      inflammation were evaluated both histologically and biochemically. Compared with
      the TNBS group, GRd treatment facilitated recovery of pathologic changes in the
      colon after induction of recurrent UC, as evidenced by a significant reduction of
      colonic weight/length ratio and macroscopic and microscopic damage scores (p <
      0.01). The myeloperoxidase and inducible nitric oxide synthase activities with
      malonyldialdehyde and nitric oxide levels in colonic tissues were significantly
      decreased in the GRd group compared with those in the TNBS group (p < 0.01). GRd
      treatment was associated with remarkably increased superoxide dismutase and
      glutathione peroxidase activities. Results showed a valuable effect of GRd
      against TNBS-induced recurrent UC by inhibiting neutrophil infiltration and
      promoting the antioxidant capacity of the damaged colonic tissue.

PMID- 22864748
TI  - In vitro activities of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone
      against non-small cell lung carcinoma.
AB  - Medicinal herbs are the preferred candidates for drug discovery against human
      diseases including cancer. The roots of Prismatomeris connata have been used in
      traditional herbal medicine to treat many health problems, particularly
      pneumoconiosis. This study was to test the anti-tumor activity of 3-hydroxy-1,5,6
      trimethoxy-2-methyl-9,10-anthraquinone (PCON6), a major anthraquinone derivative
      from C. connata, against lung cancer. Cell viability in cultures was assessed by
      MTT assay. Cell death or apoptosis was determined with annexin-V and 7
      aminoactinomycin D staining. Cell cycle was analyzed by both propidium iodide DNA
      staining and BrdU incorporation assay. Here we showed that in a panel of fifteen
      different tumor cells lines, a group of four non-small cell lung carcinoma
      (NSCLC) cell lines exhibited a relatively higher sensitivity to PCON6 growth
      inhibition than the rest of most non-lung cancer cell lines (p = 0.0461). Further
      studies demonstrated that the suppression of NSCLC H520 cell growth by PCON6 was
      associated with its induction of apoptosis at 20 MUM (p = 0.0008), and of cell
      accumulation at S phase cell cycle (p < 0.05) that was further supported by a
      decrease in cdc2 protein expression. This preliminary study suggests that natural
      compound PCON6 has relatively selective cytotoxicity against NSCLC growth and
      represent a concept of developing a novel drug therapy specific for NSCLC based
      on the roots of C. connata or PCON6.

PMID- 22864747
TI  - Protective effects of gypenosides against fatty liver disease induced by high fat
      and cholesterol diet and alcohol in rats.
AB  - In the present study, the protective effects of gypenosides from Gynostemma
      pentaphyllum on fatty liver disease (FLD) were examined in rats treated with high
      fat and cholesterol diet and alcohol. Male SD rats were divided into seven
      groups: control, model, lovastatin, silymarin, gypenosides high-, medium- and low
      treatment groups. The latter 6 groups were fed high-fat and cholesterol diet and
      administered alcohol intragastricly once a day. Body weight was measured every
      week for 10 weeks, and the hepatic index was measured after 10 weeks. Compared
      with model group, levels of serum triglyceride (TG), total cholesterol (TC), free
      fatty acid (FFA), and low density lipoprotein cholesterol (LDL-C) level,
      malondialdehyde (MDA), serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) activity, and hepatocyte apoptosis were significantly
      decreased in gypenosides groups; while serum high density lipoprotein cholesterol
      (HDL-C), superoxide dismutase (SOD) activity in both serum and hepatic tissue and
      mRNA and protein level of peroxisome proliferator-activated receptor alpha (PPAR
      alpha) were significantly increased. Moreover, hepatic steatosis and
      mitochondrial damage were improved. These results suggested that gypenosides
      could prevent liver fatty degeneration in fatty liver disease through modulating
      lipid metabolism, ameliorating liver dysfunction and reducing oxidative stress.

PMID- 22864749
TI  - The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes.
AB  - Reactive oxygen species (ROS) can induce oxidative injury via iron interactions
      (i.e. Fenton chemistry and hydroxyl radical formation). Our prior work suggested
      that American ginseng berry extract and ginsenoside Re were highly
      cardioprotective against oxidant stress. To extend this study, we evaluated the
      protective effect of protopanaxadiol-type ginsenoside Rb1 (gRb1) on H(2)O(2)
      induced oxidative injury in cardiomyocytes and explored the ROS-mediated
      intracellular signaling mechanism. Cultured embryonic chick cardiomyocytes (4-5
      day) were used. Cell death was assessed by propidium iodide and lactate
      dehydrogenase release. Pretreatment with gRb1 (0.01, 0.1, or 1 MUM) for 2 h and
      concurrent treatment with H(2)O(2) (0.5 mM) for 2 h resulted in a dose-dependent
      reduction of cell death, 36.6 +/- 2.9% (n = 12, p < 0.05), 30.5 +/- 5.1% (n = 12,
      p < 0.05) and 28.6 +/- 3.1% (n = 12, p < 0.01) respectively, compared to H(2)O(2)
      exposed cells (48.2 +/- 3.3%, n = 12). This cardioprotective effect of gRb1 was
      associated with attenuated intracellular ROS generation as measured by 6-carboxy
      2', 7'-dichlorodihydrofluorescein diacetate, preserved the mitochondrial membrane
      potential as determined using JC-1. In the ESR study, gRb1 exhibited the
      scavenging DPPH and hydroxyl radical activities. Furthermore, our data showed the
      increased JNK phosphorylation (p-JNK) in H(2)O(2)-exposed cells was suppressed by
      the pretreatment with gRb 1 (1 MUM) (p < 0.01). Co-treatment of gRb1 with a
      specific inhibitor of JNK SP600125 (10 MUM) further reduced the p-JNK and
      enhanced the cell survival after H(2)O(2) exposure. Collectively, our results
      suggest that gRb1 conferred cardioprotection that was mediated via attenuating
      ROS and suppressing ROS-induced JNK activation.

PMID- 22864750
TI  - The regulatory mechanism of 4-phenylbutyric acid against ER stress-induced
      autophagy in human gingival fibroblasts.
AB  - Endoplasmic reticulum (ER) stress is closely connected to autophagy. When cells
      are exposed to ER stress, cells exhibit enhanced protein degradation and form
      autophagosomes. In this study, we demonstrate that the chemical chaperone, 4
      phenylbutyric acid (4-PBA), regulates ER stressinduced cell death and autophagy
      in human gingival fibroblasts. We found that 4-PBA protected cells against
      thapsigargin-induced apoptotic cell death but did not affect the reduced cell
      proliferation. ER stress induced by thapsigargin was alleviated by 4-PBA through
      the regulation of several ER stress-inducible, unfolded protein response related
      proteins including GRP78, GRP94, C/EBP homologous protein, phospho-eIF-2alpha,
      eIF-2alpha, phospho-JNK1 (p46) and phospho-JNK2/3 (p54), JNK1, IRE-1alpha, PERK,
      and sXBP-1. Compared with cells treated with thapsigargin alone, cells treated
      with both 4-PBA and thapsigargin showed lower levels of Beclin-1, LC-3II and
      autophagic vacuoles, indicating that 4-PBA also inhibited autophagy induced by ER
      stress. This study suggests that 4-PBA may be a potential therapeutic agent
      against ER stress-associated pathologic situations.

PMID- 22864751
TI  - Attenuation of scopolamine-induced cognitive dysfunction by obovatol.
AB  - Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly
      people. The disease is pathologically characterized by extracellular deposition
      of beta-amyloid peptide (Abeta), cholinergic neurodegeneration and elevation of
      acetylcholine esterase (AChE) activity in the affected regions. In this study, we
      investigated the effects of obovatol on memory dysfunction, which was caused by
      scopolamine. Obovatol (0.2, 0.5 and 1 mg/kg for 7 day) attenuated scopolamine (1
      mg/kg, i.p.)-induced amnesia in a dose-dependent manner, as revealed by the
      Morris water maze test and step-through passive avoidance test. Mechanism studies
      exhibited that obovatol dose-dependently alleviated scopolamine-induced increase
      in Abeta generation and beta-secretase activity in the cortex and hippocampus.
      Obovatol also attenuated scopolamine-induced rise in AChE activity in the cortex
      and hippocampus. Obovatol might rescue scopolamine-mediated impaired learning and
      memory function by attenuating Abeta accumulation and stabilizing cholinergic
      neurotransmission, which suggests that the natural compound could be a useful
      agent for the prevention of the development or progression of AD
      neurodegeneration.

PMID- 22864752
TI  - Inhibitory effect of dibutyryl chitin ester on nitric oxide and prostaglandin E2
      production in LPS-stimulated RAW 264.7 cells.
AB  - Inflammation is a highly complex process that protects against foreign challenge
      or tissue injury. The ester derivative dibutyryl chitin (DBC) reportedly
      accelerates wound healing and exerts an anti-inflammatory effect. However, little
      is known regarding the inhibitory effect of DBC in anti-inflammation. In this
      study, we investigated the effect of DBC on the inducible nitric oxide synthetase
      (iNOS) and cyclooxygenage-2 (COX-2) pathways and pro-inflammatory cytokine
      production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results
      demonstrate that DBC (MW 3,772) significantly inhibits overproduction of NO and
      PGE(2) as well as pro-inflammatory cytokines, such as tumor necrosis factor-alpha
      and interleukin-1beta, in LPS-stimulated RAW 264.7 macrophages. Inhibition of NO
      and PGE(2) overproduction in LPSstimulated RAW 264.7 macrophages by DBC was
      mediated through the down-regulation of iNOS and COX-2 expression. These results
      demonstrate that DBC efficiently inhibits inflammation and has potential as an
      effective anti-inflammatory and wound healing agent.

PMID- 22864753
TI  - Large-scale spatial pollution patterns around the North Sea indicated by coastal
      bird eggs within an EcoQO programme.
AB  - To categorize the marine environmental health status, the Oslo and Paris
      commissions have recently formulated Ecological Quality Objectives (EcoQOs) for
      many ecological features including the contamination of coastal bird eggs with
      mercury and organochlorines. In this study, we describe spatial and temporal
      patterns of egg contamination around the North Sea and compared them to the
      EcoQOs. Concentrations of mercury, polychlorinated biphenyl (SigmaPCB) congeners,
      dichlorodiphenyltrichloroethane (SigmaDDT) and derivatives, hexachlorobenzene
      (HCB) and hexachlorocyclohexane (SigmaHCH) isomers were analysed in two tern
      species (Sterna hirundo and Sterna paradisaea) and Oystercatcher (Haematopus
      ostralegus) eggs collected between 2008 and 2010 in a total of 21 sites in seven
      countries surrounding the North Sea. Hg, SigmaPCB and HCB were highest in the
      southern sites, while SigmaDDT and SigmaHCH concentrations were greatest in eggs
      from the western North Sea and the Elbe estuary. There were rarely any consistent
      decreases over time for any compounds. In the terns, Hg, HCB and SigmaHCH
      increased at most sites, SigmaPCB and SigmaDDT in Sweden and Norway. In the
      Oystercatcher, HCB and SigmaHCH increased at more than the half of the sites,
      SigmaPCB, SigmaDDT and Hg at several German sites. In the terns, Hg, SigmaPCB and
      SigmaDDT exceeded the EcoQO in all, HCB in most years and sites. At most sites,
      SigmaHCH fulfilled the EcoQO in some study years. In the Oystercatcher, Hg,
      SigmaPCB and SigmaDDT exceeded the EcoQO in all or most years and sites. HCB and
      SigmaHCH fulfilled the EcoQO in some or all years at most sites. The EcoQO was
      exceeded most frequently in estuaries. We conclude that EcoQOs are suitable for
      drawing contamination patterns of the coastal North Sea in an easily
      understandable manner, offering the opportunity to harmonize the EcoQOs with
      coordinated environmental monitoring programmes.

PMID- 22864755
TI  - Pentachlorophenol dechlorination and simultaneous Cr6+ reduction by Pseudomonas
      putida SKG-1 MTCC (10510): characterization of PCP dechlorination products,
      bacterial structure, and functional groups.
AB  - It is the first report in which a novel psychrotrophic Pseudomonas putida SKG-1
      strain was evaluated for simultaneous bioremediation of pentachlorophenol and
      Cr(6+) under various cultural and nutritional conditions. Pentachlorophenol (PCP)
      dechlorination products, bacterial structure, and functional groups were
      characterized by gas chromatography and mass spectrometry (GC-MS), scanning
      electron microscope and energy dispersive X-ray spectroscopy (SEM-EDS), and
      Fourier-transform infrared (FTIR) techniques. The strain was extremely tolerant
      to excessively higher individual concentration of PCP (1,400 mg l(-1)) and Cr(6+)
      (4,300 mg l(-1)). Increasing concentration of PCP and Cr(6+) exerted inhibitory
      effect on bacterial growth and toxicants' removal. The strain exhibited growth,
      and concomitantly remediated both the pollutants simultaneously over a broad pH
      (7.0-9.0) and temperature (28-32  degrees C) range; maximum growth, PCP
      dechlorination (87.5%), and Cr(6+) removal (80.0%) occurred at optimum pH 8.0 and
      30  degrees C (from initial PCP 100 mg l(-1) and Cr(6+) 500 mg l(-1)) under
      shaking (150 rpm) within 72 h incubation. Optimization of agitation (125 rpm) and
      aeration (0.4 vvm) in bioreactor further enhanced PCP dechlorination by ~10% and
      Cr(6+) removal by 2%. A direct correlation existed between growth and
      bioremediation of both the toxicants. Among other heavy metals, mercury exerted
      maximum and cobalt minimum inhibitory effect on PCP dechlorination and Cr(6+)
      removal. Chromate reductase activity was mainly associated with the supernatant
      and cytosolic fraction of bacterial cells. GC-MS analysis revealed the formation
      of tetrachloro-p-hydroquinone, 2,4,6-trichlorophenol, and 2,6-dichlorophenol as
      PCP dechlorination products. FTIR spectrometry indicated likely involvement of
      carbonyl and amide groups in Cr(3+) adsorption, and SEM-EDS showed the presence
      of chromium on P. putida surface. Thus, our promising isolate can be ecofriendly
      employed for biotreatment of various industrial wastes contaminated with high PCP
      and Cr(6+) concentrations.

PMID- 22864754
TI  - Meta-analysis of environmental contamination by alkylphenols.
AB  - Alkylphenols and alkylphenol ethoxylates (APE) are toxics classified as endocrine
      disrupting compounds; they are used in detergents, paints, herbicides,
      pesticides, emulsifiers, wetting and dispersing agents, antistatic agents,
      demulsifiers, and solubilizers. Many studies have reported the occurrence of
      alkylphenols in different environmental matrices, though none of these studies
      have yet to establish a comprehensive overview of such compounds in the water
      cycle within an urban environment. This review summarizes APE concentrations for
      all environmental media throughout the water cycle, from the atmosphere to
      receiving waters. Once the occurrence of compounds has been assessed for each
      environmental compartment (urban wastewater, wastewater treatment plants [WWTP],
      atmosphere, and the natural environment), data are examined in order to
      understand the fate of APE in the environment and establish their geographical
      and historical trends. From this database, it is clear that the environment in
      Europe is much more contaminated by APE compared to North America and developing
      countries, although these APE levels have been decreasing in the last decade. APE
      concentrations in the WWTP effluent of developed countries have decreased by a
      factor of 100 over the past 30 years. This study is aimed at identifying both the
      correlations existing between environmental compartments and the processes that
      influence the fate and transport of these contaminants in the environment. In
      industrial countries, the concentrations observed in waterways now represent the
      background level of contamination, which provides evidence of a past diffuse
      pollution in these countries, whereas sediment analyses conducted in developing
      countries show an increase in APE content over the last several years. Finally,
      similar trends have been observed in samples drawn from Europe and North America.

PMID- 22864756
TI  - Heavy metal immobilization in soil near abandoned mines using eggshell waste and
      rapeseed residue.
AB  - Heavy metal contamination of agricultural soils has received great concern due to
      potential risk to human health. Cadmium and Pb are largely released from
      abandoned or closed mines in Korea, resulting in soil contamination. The
      objective of this study was to evaluate the effects of eggshell waste in
      combination with the conventional nitrogen, phosphorous, and potassium fertilizer
      (also known as NPK fertilizer) or the rapeseed residue on immobilization of Cd
      and Pb in the rice paddy soil. Cadmium and Pb extractabilities were tested using
      two methods of (1) the toxicity characteristics leaching procedure (TCLP) and (2)
      the 0.1 M HCl extraction. With 5 % eggshell addition, the values of soil pH were
      increased from 6.33 and 6.51 to 8.15 and 8.04 in combination with NPK fertilizer
      and rapeseed residue, respectively, compared to no eggshell addition. The
      increase in soil pH may contribute to heavy metal immobilization by altering
      heavy metals into more stable in soils. Concentrations of TCLP-extracted Cd and
      Pb were reduced by up to 67.9 and 93.2 % by addition of 5 % eggshell compared to
      control. For 0.1 M HCl extraction method, the concentration of 0.1 M HCl-Cd in
      soils treated with NPK fertilizer and rapeseed residue was significantly reduced
      by up to 34.01 and 46.1 %, respectively, with 5 % eggshell addition compared to
      control. A decrease in acid phosphatase activity and an increase in alkaline
      phosphatase activity at high soil pH were also observed. Combined application of
      eggshell waste and rapeseed residue can be cost-effective and beneficial way to
      remediate the soil contaminated with heavy metals.

PMID- 22864757
TI  - Photocatalytic degradation of Reactive Red 195 using anatase/brookite TiO2
      mesoporous nanoparticles: optimization using response surface methodology (RSM)
      and kinetics studies.
AB  - In the present study, the photocatalytic degradation of Reactive Red 195 (RR195)
      from aqueous samples under UV-A irradiation by using anatase/brookite TiO2 (A/B
      TiO2) mesoporous nanoparticles has been investigated. Batch experiments were
      conducted to study the effects of the main parameters affecting the
      photocatalytic process. The effects and interactions of most influenced
      parameters, such as substrate concentration and catalyst load, were evaluated and
      optimized by using a central composite design model and a response surface
      methodology. The results indicated that the dye degradation efficiency in the
      experimental domain investigated was mainly affected by the tested variables, as
      well as their interaction effects. Analysis of variance showed a high coefficient
      of determination value (R(2) = 0.9947), thus ensuring a satisfactory adjustment
      of the first-order regression model (2FI model) with the experimental data. The
      obtained results also indicate that catalyst loading plays an important role in
      determining the removal efficiency of RR195 attributable to both photodegradation
      and adsorption process. Under optimal conditions (initial dye concentration (50
      mg/L) and catalyst loading (2,000 mg/L), A/B TiO2 showed similar removal
      efficiency compared to that of commercial titania (Degussa P25). Also, at these
      conditions, complete degradation of RR195 can be achieved by both catalysts
      within 15 min under UV-A irradiation. The experiments demonstrated that dye
      removal on the prepared A/B TiO2 was facilitated by the synergistic effects
      between adsorption and photocatalysis. Photocatalytic mineralization of RR195 was
      monitored by total organic carbon. The recycling experiments confirmed the
      stability of the catalyst.

PMID- 22864758
TI  - The online poker sub-culture: dialogues, interactions and networks.
AB  - This paper examines the distinct world of online poker. It outlines the online
      poker eco-system, and the players which inhabit it, their distinctive attitudes
      and behaviors towards the game and gambling. These unique patterns of behavior
      have been created and sustained by the interaction of players within online poker
      forums. Therefore online poker forums were identified as primary mechanism within
      which a poker sub-culture may exist. The study conducted an extensive netnography
      of online poker forums. The study found that within the online poker eco-system
      there are forums which are elevated to sacred status amongst this online poker
      sub-culture. The members of these forums enact sub-cultural characteristics such
      as ethos of collaboration/cooperation, and a competitive hierarchy of status. In
      particular this paper identifies the importance of identity generation, and
      communities within the online poker eco-system. 

PMID- 22864759
TI  - Cytogenetics of Synbranchiformes: a comparative analysis of two Synbranchus
      Bloch, 1795 species from the Amazon.
AB  - Synbranchidae belongs to the Synbranchiformes and occurs in Africa, Asia,
      Australia, Mexico, and Central and South America. This family comprises four
      genera: Synbranchus, Ophisternon, Monopterus, and Macrotrema. Only two are known
      from the neotropical region, Ophisternon and Synbranchus. According to current
      classification, Synbranchus has three valid species: S. marmoratus (Bloch 1795),
      S. madeirae (Rosen and Rumney 1972), and S. lampreia (Favorito, Zanata and
      Assumpcao 2005). Thus the present research is aimed to cytogenetically
      characterize (by classical and molecular methods) two syntopic species-S. aff.
      lampreia and S. madeirae-from the central Amazon basin to validate the taxonomy
      of both species and provide a revisionary discussion on the cytogenetics of
      Synbranchiformes. Synbranchus aff. lampreia was found to possess 2n = 44
      chromosomes (6 m + 2st + 36a, NF = 50), while S. madeirae had 2n = 46 chromosomes
      (6 m + 2st + 38a, NF = 52). Constitutive heterochromatin was dominant in the
      centromeric and terminal regions of most of the chromosomes in both species,
      although the precise distribution patterns were species-specific. The nucleolar
      organizing region was single in S. aff. lampreia and multiple in S. madeirae, as
      indicated by both AgNO(3) and hybridization using 18S rDNA probes. The 5S rDNA
      sites were located interstitially on the long arms of an acrocentric pair in both
      species, and the telomeric probe did not show any interstitial sites in either
      species. These data indicate the occurrence of interspecific karyotypic
      variability in Synbranchus and suggest that taxonomic review for this genus is
      necessary.

PMID- 22864760
TI  - Surgical excision of developmental retrorectal cysts: results with long-term
      follow-up from a single institution.
AB  - Developmental cysts are very rare lesions occurring in the retrorectal space, and
      include epidermoid, dermoid, tailgut cysts and teratomas. There is little
      information on their natural history and biologic behavior, although a recent
      paper reported a greater incidence of malignant transformation than previously
      thought. The diagnosis requires high-resolution imaging, and complete surgical
      excision is the treatment of choice. In this paper we analyzed short- and long
      term results of surgical excision of six retrorectal developmental cysts observed
      at our institution over a period of 11 years. All patients were women, three were
      referred with an infected perineal fistula/pelvic abscess after having undergone
      drainage surgery elsewhere. In these three patients, excision was attempted
      through a trans-perineal approach, which was technically demanding and ultimately
      incomplete because of the intense surrounding inflammation. Multiple re
      interventions were required for tumor recurrence, and two of them still present
      an occasional perineal discharge. In the other three patients, a trans-perineal
      or trans-anal route was employed according to tumor location, without any
      recurrence at a median follow-up of 118.5 months. Final pathologic diagnosis
      included five tailgut cysts and one teratoma. This paper shows that the treatment
      of developmental cysts may be very challenging, especially when they are
      associated with a concomitant fistula/abscess and are not correctly diagnosed at
      presentation. In our experience, healing was finally achieved in four patients
      out of six. All the lesions were benign, and no malignant transformation was
      observed during follow-up, even in tumors partially resected.

PMID- 22864761
TI  - Real-world costs of autologous and allogeneic stem cell transplantations for
      haematological diseases: a multicentre study.
AB  - Haematopoietic stem cell transplantation (SCT) is an expensive lifesaving
      procedure, which is increasingly performed in patients with haematological
      diseases. Developments in the protocol for SCT have resulted in cost estimates
      that require updating. We aimed to calculate actual costs for SCT and to identify
      major cost drivers by means of a daily practice cost study. We randomly selected
      191 patients, treated at three university hospitals, who underwent an autologous
      (auto) SCT or allogeneic (allo) SCT in 2007, 2008 or 2009. Allo-SCT included
      sibling donors, matched unrelated donors (MUD) and umbilical cord blood (UCB).
      Resource use was collected from the hospital registration systems and medical
      files. The total costs included selection and harvesting of stem cells,
      transplantation and 1-year follow-up. The average costs per patient were 45,670 ?
      for auto-SCT and 101,919 ? for sibling allo-SCT. The costs of transplantations
      from unrelated donors were much higher: 171,478 ? for allo-SCT-MUD and 254,689 ?
      for allo-SCT-UCB. Hospital inpatient days together with laboratory and other
      activities were the main cost drivers across all types of SCT. Besides, donor
      search costs were a large cost component in allo-SCT-sib (18 %) and allo-SCT-MUD
      (12 %). Real-world costs were above routine reimbursement and appropriate
      financing is necessary to guarantee the continuation of SCT. The costs calculated
      in this study provide reliable up-to-date input for cost-effectiveness studies
      and budget revision.

PMID- 22864762
TI  - A unique pattern of extranodal involvement in Korean adults with sporadic Burkitt
      lymphoma: a single center experience.
AB  - Extranodal involvement is common in patients with Burkitt lymphoma (BL). We
      evaluated the pattern of extranodal involvement and its impact on clinical
      outcomes in a single center cohort of adult Korean patients with sporadic BL. We
      retrospectively identified 64 patients with BL in the registry of non-Hodgkin
      lymphoma of the Asan Medical Center between 1996 and 2009. We assessed their
      clinical features and distribution of extranodal sites and analyzed clinical
      outcomes, including complete response rate after chemotherapy, overall survival,
      and progression-free survival, relative to baseline characteristics and involved
      extranodal sites. Extranodal involvement was found in 57 patients (89 %), with 34
      (53.1 %) having two or more extranodal sites. The stomach (26.6 %) was the most
      common site, followed by the small and large intestines (25 %), bone marrow (23.4
      %), genitourinary tract (21.9 %), and bones (18.8 %). Two patients (3.1 %) showed
      central nervous system (CNS) involvement. Complete response rates to chemotherapy
      were not related to sites of extranodal involvement. Two-year overall survival
      rates were lower in patients with bone marrow (33.3 vs. 74.6 %, p = 0.010) and
      CNS (0.0 vs. 66.6 %, p = 0.048) involvement than in patients with involvement at
      other extranodal sites. The stomach, genitourinary tract, and bones were the most
      commonly involved extranodal sites in Korean BL patients, but site had no
      prognostic significance.

PMID- 22864763
TI  - Transient lupus anticoagulant with a prolonged activated partial thromboplastin
      time secondary to cytomegalovirus-related infectious mononucleosis.

PMID- 22864765
TI  - Regulatory frameworks for cell therapy products in Japan.
AB  - This paper reviews regulatory frameworks for cell therapy products in Japan. Two
      procedures are used to investigate the use of new cell therapy products in Japan.
      One is to perform clinical trials in accordance with the provisions of the
      Pharmaceuticals Affairs Act (PAA); the other is to perform clinical research in
      accordance with the provisions of the Medical Practitioners Act. For full
      commercialization of medical products in Japan, we must consider the universal
      health care system. All medical products used to treat patients in the system
      must be approved, in accordance with the provisions of the PAA, as drugs or
      medical devices. Thus, researchers in academia who have developed new cell
      therapy products should consider performing clinical trials in accordance with
      the provisions of the PAA to test their products clinically. This article
      describes development and review processes for new drug/device applications in
      accordance with the provisions of the PAA and gives an example of clinical review
      of a cell therapy product by the Pharmaceuticals and Medical Devices Agency.

PMID- 22864764
TI  - A randomised controlled trial of abdominal versus laparoscopic sacrocolpopexy for
      the treatment of post-hysterectomy vaginal vault prolapse: LAS study.
AB  - INTRODUCTION AND HYPOTHESIS: This prospective multi-centre true two-sided
      equivalence trial was designed to test the clinical equivalence of open (ASCP)
      and laparoscopic (LSCP) sacrocolpopexy using objective and subjective outcomes
      METHODS: The study was carried out in three urogynaecology units in England, UK
      and the patient population consisted of women referred with symptomatic and
      bothersome post-hysterectomy vaginal vault prolapse at least 1 cm above or beyond
      the hymeneal remnants. The interventions were either abdominal or laparoscopic
      sacrocolpopexy following randomisation to one of the types of surgery. RESULTS:
      For the primary outcome (point C on the POP-Q) the results at 1 year were -6.63
      cm for the open ASCP and -6.67 cm for the LSCP respectively. Subjective outcomes
      at 1 year showed that 90% of the ASCP group and 80% of the LSCP group were "much
      better". There were improvements with regard to blood loss, haemoglobin and
      shorter length of stay in the LSCP group compared with the ASCP group.
      CONCLUSION: This fully powered randomised controlled trial comparing open and
      laparoscopic sacrocolpopexy has shown clinical equivalence.

PMID- 22864766
TI  - Repeated courses of ibuprofen are effective in closure of a patent ductus
      arteriosus.
AB  - Patent ductus arteriosus (PDA) is a frequent complication in preterm infants.
      Ibuprofen and indomethacin (both COX inhibitors) are used for pharmacological
      closure of PDA. In most centers, a failed second course of COX inhibitors is
      followed by surgical closure. Our aim was to estimate the closure rate of
      clinically significant PDA after second and third courses of ibuprofen and record
      possible side effects. A study population, consisting of 164 preterm infants (<32
      weeks' gestational age) with PDA admitted at our tertiary care center between
      November 2005 and September 2011, was retrospectively analyzed. Primary outcome
      was the closure rate after repeated courses of ibuprofen. The closure rate was
      similar after the first (109/164), second (24/43), and third (6/11) course of
      ibuprofen (X(2) = 2.1, p = 0.350). Late start of the first course of ibuprofen
      was a predictive factor for increased need of a second course (X(2) = 4.4, p =
      0.036). No additional side effects of multiple courses of ibuprofen were
      detected. In conclusion, repeated courses of ibuprofen are an effective and safe
      alternative for surgical closure and should be considered after failure of the
      first course of ibuprofen.

PMID- 22864767
TI  - The electronic structure of the lutein triplet state in plant light-harvesting
      complex II.
AB  - Carotenoid molecules are essential for the life of photosynthetic organisms in
      that they protect the cell from the photo-oxidative damage induced by light
      stress conditions. One of the photo-protective mechanisms involves triplet
      triplet energy transfer from the chlorophyll molecules to the carotenoids: a
      process that is strongly dependent on the electronic properties of the triplet
      states involved. Here, we obtain a clear description of the triplet state of
      lutein in LHCII from higher plants for the first time by density functional
      theory (DFT) calculations. DFT predictions have been validated by comparison with
      hyperfine couplings obtained with pulsed-ENDOR spectroscopy. Knowledge of the
      spin density distribution, the frontier orbitals and orbital excitations forms a
      basis for discussing the requirements for an efficient triplet-triplet energy
      transfer. The results obtained for the lutein in LHCII are compared with those of
      the highly-substituted carotenoid peridinin in PCP from Amphidinium carterae [Di
      Valentin et al., Biochim. Biophys. Acta, 2008, 1777, 295-307]. The presence of
      substituents in the peridinin molecule does not alter significantly the triplet
      state electronic structure compared to lutein. Despite the unusual spectroscopic
      behaviour of the peridinin excited singlet state, lutein and peridinin have
      similar triplet state properties. In both molecules the unpaired spins are
      delocalized uniformly over the whole pi-conjugated system in an alternating even
      odd pattern.

PMID- 22864768
TI  - [Minimally invasive fixation of calcaneal fractures].
AB  - OBJECTIVE: Anatomic reduction of displaced calcaneal fractures with minimal soft
      tissue alteration. INDICATIONS: Extra-articular and selected intra-articular
      calcaneal fractures (simple fracture pattern: Sanders type II, critical soft
      tissue conditions, contraindications to open reduction), temporary stabilization
      of complex injuries or polytraumatized patients. CONTRAINDICATIONS: Impossible
      percutaneous reduction and fixation. SURGICAL TECHNIQUE: Gross reduction of the
      main fragments is achieved with a Schanz screw introduced percutaneously into the
      tuberosity fragment. Fine reduction is obtained through percutaneous manipulation
      of the fragments wit Kirschner wires, Steinmann pins, sharp and smooth elevators
      via stab incisions. Anatomic reduction of the subtalar joint is controlled
      arthroscopically in cases of displaced intra-articular fractures. Fixation is
      achieved with screws introduced percutaneously. POSTOPERATIVE MANAGEMENT: Early
      range of motion exercises of the ankle and subtalar joints are initiated the
      first postoperative day. Beginning on postoperative day 2, patients are mobilized
      with partial weight bearing for 6-8 weeks. As soon as the edema has subsided,
      patients are encouraged to wear their own shoes. RESULTS: Between 1998 and 2008,
      68 patients were treated with definite percutaneous fixation for displaced
      calcaneal fractures. In 37 patients with intraarticular fractures (Sanders types
      IIA and IIB), anatomic joint reduction was verified with subtalar arthroscopy. No
      soft tissue-related complications were observed. Thirty-five patients were
      followed for a minimum of 2 years postoperatively, the average was 5 years
      postoperatively. Subjectively, 33 of 35 patients were satisfied with the clinical
      outcome. The AOFAS Hindfoot Score averaged 90.7 (range 64-100) at a mean of 5
      years after surgery. Percutaneous screw fixation of calcaneal fractures is
      associated with minimal soft tissue traumatization and low complication rates. It
      allows early rehabilitation and excellent results with proper patient selection.
      With intra-articular fractures, proper reduction of the articular surface has to
      be confirmed intraoperatively.

PMID- 22864769
TI  - TOP2A amplification in breast cancer is a predictive marker of anthracycline
      based neoadjuvant chemotherapy efficacy.
AB  - Anthracycline is a DNA topoisomerase 2-alpha (TOP2A) inhibitor and its
      concomitant over expression with Human Epidermal Growth Factor Receptor 2 (HER2)
      was investigated of being predictive for the response to anthracycline-based
      chemotherapies in breast cancer. 309 early and local advanced breast cancer
      patients were treated with anthracycline-based neoadjuvant chemotherapies in
      intense dose dense (IDD) (CE, Cyclophosphamide + Epirubicin) or conventional (TE,
      Paclitaxel + Epirubicin) regimens. HER2 proteins were qualitatively analyzed by
      immunohistochemistry (IHC) of primary tumor core biopsies, and TOP2A gene
      amplification levels of HER2 over-expressing cases were quantified by
      quantitative real-time polymerase chain reaction (qRT-PCR). Overall pathological
      complete response rate (pCR) was achieved in 14.3 %. HER2 was over expressed in
      80/309 (25.9 %) cases, of which 61/80 cases have been tested for their TOP2A
      status. Over expression of HER2 was significantly positively correlated with
      higher pCR rates compared to low HER2 expression (27.5 % vs. 9.6 %, P < 0.001).
      Concurrent high TOP2A amplification led to a significantly higher pCR rate
      compared to low or no TOP2A amplification (56.3 % vs. 13.8 %, P = 0.001). HER2
      over expression was associated with a significantly higher pCR rate only when
      TOP2A was also amplified (56.3 % vs. 9.6 %, P < 0.001), but not when it was
      deleted or normal (13.8 % vs. 9.6 %, P = 0.183) compared to HER2 low-expressing
      tumors. The interaction between HER2 or TOP2A and anthracycline-based regimen was
      observed in IDD and conventional neoadjuvant chemotherapies. The TOP2A
      amplification is related to anthracycline-based neoadjuvant chemotherapy
      sensitivity, and TOP2A should be included in future studies in breast cancer as a
      predictive marker.

PMID- 22864771
TI  - Exploring and mapping the world of astrocytes.

PMID- 22864770
TI  - Mammographic density and breast cancer risk in White and African American Women.
AB  - Mammographic density is a strong risk factor for breast cancer, but limited data
      are available in African American (AA) women. We examined the association between
      mammographic density and breast cancer risk in AA and white women. Cases (n =
      491) and controls (n = 528) were from the Carolina Breast Cancer Study (CBCS) who
      also had mammograms recorded in the Carolina Mammography Registry (CMR).
      Mammographic density was reported to CMR using Breast Imaging Reporting and Data
      System (BI-RADS) categories. Increasing mammographic density was associated with
      increased breast cancer risk among all women. After adjusting for potential
      confounders, a monotonically increasing risk of breast cancer was observed
      between the highest versus the lowest BI-RADS density categories [OR = 2.45, (95
      % confidence interval: 0.99, 6.09)]. The association was stronger in whites, with
      ~40 % higher risk among those with extremely dense breasts compared to those with
      scattered fibroglandular densities [1.39, (0.75, 2.55)]. In AA women, the same
      comparison suggested lower risk [0.75, (0.30, 1.91)]. Because age, obesity, and
      exogenous hormones have strong associations with breast cancer risk, mammographic
      density, and race in the CBCS, effect measure modification by these factors was
      considered. Consistent with previous literature, density-associated risk was
      greatest among those with BMI > 30 and current hormone users (P value = 0.02 and
      0.01, respectively). In the CBCS, mammographic density is associated with
      increased breast cancer risk, with some suggestion of effect measure modification
      by race, although results were not statistically significant. However, exposures
      such as BMI and hormone therapy may be important modifiers of this association
      and merit further investigation.

PMID- 22864772
TI  - Rodent model of nonarteritic ischemic optic neuropathy and its
      electrophysiological evaluation.
AB  - PURPOSE: Our aim was to establish a rodent model of nonarteritic ischemic optic
      neuropathy (rNAION). METHODS: To induce rNAION, after administration of Rose
      Bengal (RB) (2.5 mM), the small vessels of the left optic nerve were
      photoactivated using a 514-nm argon green laser with about 500-MUm spot size for
      12 s (RB-laser induction). To evaluate the induction, funduscopic examination,
      fluorescein angiography (FA), visualization of capillaries within the optic disc,
      histologic evaluation, and electrophysiological testing were performed. RESULTS:
      In the RB-laser-induction eyes, the optic disc became swollen on day 3 followed
      by atrophy on week 8. FA showed filling defects in the choroid and optic disc at
      an early stage, followed by hyperfluorescence at a late stage. The capillaries
      within the optic disc were reduced markedly. Histopathologic examination showed
      acellular nerve fiber layer (NFL) swelling anterior to the optic disc. The
      morphologic retinal changes were apparent only in the retinal ganglion cell (RGC)
      layer, with a reduction in the number of cells. Visually evoked potential (VEP)
      amplitude decreased significantly, but electroretinography (ERG) showed no
      significant difference. The positive scotopic threshold response (pSTR) was not
      reduced on the 1st day but was significantly reduced 3 days after induction.
      CONCLUSIONS: The findings are similar to human NAION. Therefore, RB-laser
      induction is well suited to establish the presence of rNAION.

PMID- 22864773
TI  - Azo-hydrazone tautomerism observed from UV-vis spectra by pH control and metal
      ion complexation for two heterocyclic disperse yellow dyes.
AB  - The azo-hydrazone tautomerism of two pyridine-2,6-dione based Disperse Yellow
      dyes has been achieved by pH control and metal-ion complexation, respectively,
      which is evidenced by UV-visible spectra using pH-titration, (1)H NMR and X-ray
      single-crystal diffraction techniques for two dyes and one neutral dinuclear dye
      metal complex. pH-titration experiments under strong and weak acidic conditions
      (HCl and HOAc) as well as strong and weak alkaline conditions (NaOH and ammonia)
      demonstrate that there is an equilibrium between the azo (HL(1-A) and HL(2-A))
      and hydrazone (HL(1-H) and HL(2-H)) tautomers for two dyes in solution but the
      hydrazone form is dominant under conventional conditions. The hydrazone proton is
      also observed in the (1)H NMR spectra of HL(1-H) and HL(2-H) which can be
      verified by the hydrogen-deuterium exchange and the presence of cooperative six
      membered intramolecular hydrogen rings involving the hydrazone proton in their X
      ray single-crystal structures. Moreover, the azo-hydrazone tautomerism is
      evidenced by the formation of a novel neutral dinuclear dye-metal complex
      Cu(2)(L(2-A))(4), where all the ligands are in the azo form and two types of
      coordination modes are present for four L(2-A) ligands. Namely, the side two
      ligands serve as the bidentate capping ligands, while the middle ones act as the
      quadridentate bridging ligands linking adjacent Cu(II) centers in a reverse
      fashion.

PMID- 22864774
TI  - The many faces of plectin and plectinopathies: pathology and mechanisms.
AB  - Plectin, a giant multifunctional cytolinker protein, plays a crucial role in
      stabilizing and orchestrating intermediate filament networks in cells. Mutations
      in the human plectin gene result in multiple diseases manifesting with muscular
      dystrophy, skin blistering, and signs of neuropathy. The most common disease
      caused by plectin deficiency is epidermolysis bullosa simplex (EBS)-MD, a rare
      autosomal-recessive skin blistering disorder with late-onset muscular dystrophy.
      EBS-MD patients and plectin-deficient mice display pathologic desmin-positive
      protein aggregates, degenerated myofibrils, and mitochondrial abnormalities, the
      hallmarks of myofibrillar myopathies. In addition to EBS-MD, plectin mutations
      have been shown to cause EBS-MD with a myasthenic syndrome, limb-girdle muscular
      dystrophy type 2Q, EBS with pyloric atresia, and EBS-Ogna. This review focuses on
      clinical and pathological manifestations of these plectinopathies. It addresses
      especially plectin's role in skeletal muscle, where a loss of muscle fiber
      integrity and profound changes of myofiber cytoarchitecture are observed in its
      absence. Furthermore, the highly complex genetic and molecular structure of
      plectin is discussed; a high number of differentially spliced exons give rise to
      a variety of different isoforms, which fulfill distinct functions in different
      cell types and tissues. Plectin's abilities to act as a dynamic organizer of
      intermediate filament networks and to interact with a multitude of different
      interaction partners are the basis for its function as a scaffolding platform for
      proteins involved in signaling. Finally, the article addresses a series of
      genetically manipulated mouse lines that were generated to serve as powerful
      models to study functional and molecular consequences of plectin gene defects.

PMID- 22864775
TI  - Invasive lobular carcinoma of the breast: cytometric and immunohistochemical
      characteristics of 96 cases.
AB  - The aim of the study was to present microscopic, cytometric and
      immunohistochemical characteristics of a group of 96 invasive lobular carcinomas
      (ILC) of the breast. Ninety six patients treated surgically at the Department of
      Surgical Oncology, Centre of Oncology - Maria Sklodowska-Curie Memorial
      Institute, Cracow Branch, between 1983 and 1996, were included into the study. In
      56 (58.3%) cases, a classical pattern of ILC was diagnosed, whereas atypical
      variants (solid, pleomorphic, pleomorphic with signet ring cells, signet ring
      cell, and tubulolobular) were recognized in 40 (41.7%) cases. ILC was
      characterized by lack of E-cadherin expression, high rate of steroid receptor
      expression, low rate of P53 and c-erb-B2 expressing tumours, low MIB-1 labelling
      index, and low S phase fraction, as well as high rate of diploid lesions.

PMID- 22864776
TI  - Colorectal cancers differ in respect of PARP-1 protein expression.
AB  - Recent findings raise the possibility of PARP inhibitor therapy in colorectal
      cancers (CRCs). However, the extent of PARP-1 protein expression in clinical
      specimens of CRC is not known. Using immunohistochemistry we assessed PARP-1
      protein expression in tissue microarrays of 151 CRCs and its association with the
      patient's age, sex, Astler-Coller stage, grade and site of the tumor. High PARP
      nuclear immunoreactivity was found in 68.2% (103/151) of all cases. In turn,
      31.8% (48/151) of tumors showed low PARP expression, including 9 (6%) PARP-1
      negative CRCs. There was a significant association of PARP-1 expression with the
      site of CRC and Astler-Coller stage. A high PARP expression was noted in 79.1% of
      colon vs. 53.9% of rectal tumors (p = 0.001). The mean PARP-1 score was 1.27
      times higher in colon vs. rectal cancers (p = 0.009) and it was higher in stage
      B2 vs. stage C of CRCs  (p = 0.018). In conclusion, the level of PARP-1 protein
      nuclear expression is associated with the tumor site and heterogeneous across
      clinical specimens of CRC, with the majority of CRCs expressing a high level but
      minority - low or no PARP-1 expression. These findings may have a clinical
      significance because the assessment of PARP-1 expression in tumor samples may
      improve selection of patients with CRC for PARP inhibitor therapy.

PMID- 22864778
TI  - Correlation of SATB1 expression with clinical course of cutaneous T-cell
      lymphomas.
AB  - Cutaneous T-cell lymphomas (CTCLs) are slowly progressive diseases with a poor
      prognosis. There are no specific prognostic factors in development of cutaneous
      lymphomas. SATB1 protein controls expression of many genes, including the
      cellular cycle and apoptosis. The subject of our study was the expression of
      SATB1 protein in the skin sample in patients with mycosis fungoides and Sezary
      syndrome and its correlation with clinical course. Immunohistochemical reaction
      with SATB1 antibody was observed in 29 cases of mycosis fungoides of different
      stages (15 patients) and two cases of Sezary syndrome. SATB1 expression was
      observed in 22 cases of mycosis fungoides, 7 of which were in the patch stage, 11
      were in the plaque stage and 4 were in the tumor stage. SATB1 expression was not
      found in 2 cases of the patch stage, 4 cases of the plaque stage and one case of
      the tumor stage. Negative reaction was confirmed in both cases of the Sezary
      syndrome. There were no changes in SATB1 expression during progression of the
      disease. A group of patients with the positive reaction of the SATB1 is
      characterized by a noticeably longer time to progression between the stages. The
      SATB1 expression seems to be a potential prognosis factor confirming the inner
      heterogeneous features of CTCLs.

PMID- 22864777
TI  - Clinical-pathological correlation of K-Ras mutation and ERK phosphorylation in
      colorectal cancer.
AB  - The Ras-ERK pathway is frequently up-regulated in colorectal cancer. We analyzed
      the clinical-pathological correlation of K-Ras mutation and phospho-ERK
      expression in colorectal cancer. K-Ras mutations were detected in only 32.5%
      (41/126) of the colorectal cancer cases, while all cancers were positive for
      phospho-ERK staining. Colorectal cancer with wild-typeK-Ras and low phospho-ERK
      expression had a significantly higher survival rate (log-rank P = 0.04). There
      were 9 cases of K-Ras mutation/low phospho-ERK diseases; 88.9% (8/9) of them were
      stage III/IV diseases. High phospho-ERK expression was associated with a high
      stage and T status of the cancer, yet combined K-Ras mutation/phospho-ERK
      expression analysis further increased the efficiency of colorectal cancer
      prognosis. Our results demonstrate that Ras-ERK pathway correlated closely with
      colorectal cancer progression. Moreover, although colorectal cancer with K-Ras
      mutations has a more aggressive phenotype; the mutation rate is not very high.
      Phospho-ERK may be a useful marker in combination with K-Ras for improving the
      prognosis of colorectal cancer.

PMID- 22864779
TI  - Sporadic mutations and expression analysis of spleen tyrosine kinase gene in
      breast cancer: a preliminary report.
AB  - Spleen tyrosine kinase (Syk) is an intracellular receptor protein kinase involved
      in cell proliferation, differentiation and phagocytosis. Syk expression has been
      reported in cell lines of epithelial origin. The strong expression of Syk in
      mammary gland prompted research into its potential role in mammary
      carcinogenesis. Fresh Biopsy samples were collected from different hospitals of
      Pakistan. Single stranded conformational polymorphism and Semi quantitative
      reverse transcriptase polymerase chain reaction was used to investigate somatic
      mutations and expression alterations in twenty five breast cancer tumor tissues
      along with their adjacent normal control tissue. Statistical analysis was
      performed to explore Syk association with breast cancer risk. In the present
      study, DNA from tumor tissue was analyzed and mutations in the coding sequence
      and intronic sequence spanning the exonic region of the Syk gene were identified.
      Sequence analysis revealed two missense: g61096G>A, g65967G>A, one frame shift:
      g87413insA and one silent mutation g42841G>A in exonic region while nucleotide
      variations were also observed in intronic region including one splice site
      mutation. These mutations in Syk are first time being reported in breast cancer.
      In addition, this study also revealed that Syk mRNA expression was markedly
      reduced in tissues of breast cancer compared to their adjacent normal control
      tissue.

PMID- 22864780
TI  - Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast
      cancer risk in Polish women.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in DNA repair genes may be
      associated with differences in the repair efficiency of DNA damage and may
      influence an individual's risk of cancer. The XRCC3 protein plays a critical role
      in Homologous Recombination Repair (HRR) accounting for repair of DNA double
      strand breaks (DSB). AIM: The aim of the present study was to evaluate
      associations between the risk of breast cancer and Thr241Met polymorphism in the
      XRCC3 gene. MATERIAL AND METHODS: Single nucleotide polymorphism was genotyped by
      the PCR-RFLP (restriction fragment-length polymorphism) method in 760 women with
      sporadic breast cancer and in 760 control samples. The present study confirmed a
      relationship between XRCC3 Thr241Met polymorphism and breast cancer progression,
      assessed by the degree of lymph node metastases and histological stages.
      CONCLUSION: Our findings suggest that the analysis of XRCC3 polymorphism, may
      contribute to better understanding of the mechanisms of breast cancer by
      evaluating possible interactions between these genotypes and well-established
      risk factors for breast cancer.

PMID- 22864781
TI  - Ki-67 and p53 expression in ileal pouches.
AB  - Development of dysplastic lesions that may potentially lead to cancer is
      sometimes reported within the ileal pouches. Dysplasia is in turn associated with
      increased expression of proliferation indices. The goal of this study was to
      evaluate the mitotic activity and possible expression of p53 in the epithelium
      within the ileal pouches in patients with chronic ulcerative colitis.  The study
      involved archive material consisting of ileal pouches surgically removed from 17
      patients diagnosed with ulcerative colitis. Several specimens were collected from
      each pouch. The immunohistochemistry (Ki-67 and p53 protein) control group (14
      cases) consisted of the resection line specimens of colons removed due to
      colorectal adenocarcinoma. Intensity of the expression of the markers under study
      within the inflammatory infiltrates was assessed using a 5-point scale proposed
      by Berstein et al.  Ki-67 expression was observed in all studied patients with
      marked intensity (Bernstein scale score +3, +4). Protein p53 expression was
      observed only in eight patients, and was mostly of low intensity (Bernstein scale
      score +1, +2).  Immunohistochemical results confirmed the histopathological
      results that revealed dysplastic lesions, which are often an indication for
      radical procedures in ulcerative colitis patients.  Our results suggest the
      usefulness of these examinations, also in the ileal pouch material.

PMID- 22864782
TI  - Myofibroblastoma: a potential pitfall in core needle biopsy of breast lesions.
AB  - Myofibroblastoma (MFB) is a benign neoplasm arising most frequently in the adult
      breast, but it may occur in any other tissue with the exception of the central
      nervous system. Adequate treatment of this neoplasm consists of local excision.
      MFB shows characteristic histological features and a clear immunohistochemical
      profile and usually does not cause any diagnostic difficulties [1-4]. A rare
      variant of MFB such as the epithelioid subtype with sclerotic stroma, however,
      can resemble lobular carcinoma in routinely stained histological sections.

PMID- 22864783
TI  - When "diabetic nephropathy" is not always of diabetic origin: a case report.
AB  - The etiology and pathogenesis of fibrillary glomerulonephritis (FGN) remains
      unknown. The presented case shows an extremely rare FGN in association with
      commonly diagnosed diabetes. A 74-year-old, non-smoking, obese and diabetic woman
      was hospitalized due to a progressive and accelerated decrease in the renal
      function. The primary cause of chronic kidney disease was believed to be of
      diabetic origin. In the renal biopsy, light microscopy showed glomerular changes
      resembling diabetic nephropathy, however electron microscopy evaluation revealed
      linear, randomly arranged fibrils present in the glomerular mesangium and in
      peripheral capillary loops. The biopsy confirmed fibrillary glomerulopathy.

PMID- 22864784
TI  - Hobnail hemangioma.
AB  - We present a case of a 73-year-old woman who developed a small lesion on her
      tongue. The nodule was resected and hobnail hemangioma was diagnosed. Hobnail
      hemangioma is a rare vascular lesion with unusual morphology, including bland
      cells with hobnail appearance, biphasic grow pattern with superficial dilated
      vessels and slit-like vessels in the deeper portion of the lesion. The
      infiltrative pattern of grow may cause misdiagnosis. The differential diagnosis
      with hemangioendothelioma variants, low grade angiosarcomas and Kaposi sarcoma is
      of particular concern. The lack of recognition of this uncommon entity may result
      in excessive and unnecessary treatment.

PMID- 22864785
TI  - Quiz. What is your diagnosis?

PMID- 22864786
TI  - Role of concomitant tricuspid surgery in moderate functional tricuspid
      regurgitation in patients undergoing left heart valve surgery.
AB  - Functional tricuspid regurgitation (FTR) is frequently present in patients
      undergoing aortic, and particularly mitral valve, surgery. Untreated FTR may lead
      to right heart failure. Reoperative cardiac surgery for late FTR is associated
      with high morbidity and mortality. Therefore, severe FTR has emerged as a Class I
      indication for concomitant tricuspid valve surgery in patients undergoing left
      valve surgery. Concomitant tricuspid valve surgery during left heart valve
      surgery to address moderate and mild FTR is controversial. This review addresses
      this issue and proposes an algorithm for the treatment of FTR in patients
      undergoing left heart valve surgery.

PMID- 22864787
TI  - Complications after endovascular repair of Stanford type A (ascending) aortic
      dissection.
AB  - Endovascular treatment has emerged as a less traumatic alternative treatment for
      several diseases of the thoracic aorta. However, the complications of the
      endovascular management of ascending aortic dissections are still high. We
      present a case of two iatrogenic complications after endovascular repair (EVAR)
      of type A (ascending) aortic dissection. Retrograde aortic dissection at the
      proximal part of the aortic endovascular graft and a guidewire-induced iatrogenic
      left ventricular pseudoaneurysm were presented in this patient after the stent
      grafting procedure. Fourteen months later, surgical replacement of the ascending
      aorta and proximal arch was performed and the left ventricular pseudoaneurysm was
      treated successfully by linear closure. The patient recovered uneventfully.
      Although aortic endovascular grafting is apparently less traumatic, indications
      and potential complications related to the stent graft should be considered with
      great care.

PMID- 22864788
TI  - Global gene expression differentiating pure bronchioloalveolar carcinoma from
      adenocarcinoma with bronchioloalveolar carcinoma features.
AB  - OBJECTIVES: Pure bronchioloalveolar carcinoma (BAC) is considered the early stage
      of lung adenocarcinoma, and is even regarded as lung adenocarcinoma in situ. This
      study was designed to investigate the differences in the gene expression of pure
      BAC and that of adenocarcinoma with bronchioloalveolar features and explore the
      mechanism of BAC progression to adenocarcinoma with bronchioloalveolar features
      METHODS: Total RNA was extracted from 16 tissue specimens. Expression analysis
      was carried out using Agilent 4 * 44 k arrays. Gene ontology analysis was used to
      define pathways altered in bronchioloalveolar progression. Differentially
      expressed candidate genes were validated using quantitative real-time PCR. The
      statistical analysis was carried out according to the methods of the paired t
      test. RESULTS: Adenocarcinoma with bronchioloalveolar features demonstrated an
      increased expression of 23 genes and reduced expression of 20 genes compared with
      BAC. These genes were considered candidate marker genes for tumour progression
      and metastasis. Genes overexpressed in adenocarcinoma with bronchioloalveolar
      features included fibroblast growth factor receptor 1, and CLDN18 (claudin 18),
      whereas those overexpressed in BAC included ataxia telangiectasia and Rad3
      related (ataxia telangiectasia mutated and Rad3-related), and activating
      transcription factor 2. Mitogen-activated protein kinase (MAPK) pathway seemed
      dysregulated in adenocarcinoma with bronchioloalveolar features compared with
      pure BAC. CONCLUSIONS: Microarray-based expression profiling revealed interesting
      novel candidate genes in BAC and adenocarcinoma with bronchioloalveolar features.
      The MAPK pathway seemed dysregulated in adenocarcinoma with bronchioloalveolar
      features compared with the pure BAC pathway, which is worthy of being explored
      because it could partially explain the mechanism of the progression of BAC to
      adenocarcinoma with bronchioloalveolar features.

PMID- 22864789
TI  - Evaluation of risk factors for transient neurological dysfunction and adverse
      outcome after repair of acute type A aortic dissection in 122 consecutive
      patients.
AB  - OBJECTIVES: The aim of this retrospective study was to assess pre- and
      intraoperative factors leading to neurological complications and early death
      following repair of acute type A aortic dissection (ATAAD). METHODS: There were
      122 patients (85 male, age: 58.6 +/- 12.5 years) with ATAAD, treated
      consecutively from August 2003 to August 2010. Pre- and intraoperative variables
      were analysed using a logistic regression model in order to identify risk factors
      for temporary neurological dysfunction (TND) and adverse outcome (AO), defined as
      stroke and 30-day mortality. RESULTS: The 30-day mortality rate was 16.4%. Forty
      one patients (33.6%) suffered transient neurological dysfunction and 20 (16.4%)
      had a postoperative stroke. Mean hypothermic circulatory arrest (HCA) temperature
      was 24 +/- 4  degrees C. Selective cerebral perfusion (SCP) was performed in 99
      (82%) patients, with a mean SCP flow rate of 10.3 ml/kg/min. The duration of
      lower body ischaemia (LBI) was 36 +/- 27 min, of HCA 8.7 +/- 15.5 min and of SCP
      34 +/- 28 min, respectively. Male gender [odds ratio (OR): 3.30, 95% confidence
      interval (CI): 1.15-9.47], diabetes (OR: 3.95, 95% CI: 1.18-13.24), compromised
      consciousness (OR: 6.65, 95% CI: 1.41-31.48) and manifest arterial
      atherosclerosis (OR: 6.68, 95% CI: 1.31-34.09) were detected as risk factors for
      TND, whereas a high body mass index (OR: 1.14, 95% CI: 1.01-1.3), a preoperative
      malperfusion syndrome (OR: 2.28, 95% CI: 0.84-6.18) and left ventricular ejection
      fraction <50% (OR: 3.84, 95% CI: 1.41-10.43) were detected as independent
      predictors for an AO. A dissection entry localized in the aortic arch or the
      descending aorta independently increased the risk for a postoperative stroke. A
      prolonged LBI increased the risk for AO (OR: 1.02, 95% CI: 1.00-1.04), whereas
      femoral cannulation showed a trend to an increased stroke incidence (OR: 4.2, 95%
      CI: 0.8-21.3). CONCLUSIONS: Regardless of standardized neuroprotective
      techniques, treatment of ATAAD remains a high-risk operation. Preoperatively, the
      presence of a reduced ejection fraction, a malperfusion syndrome or a high body
      mass index may increase the perioperative risk for an adverse outcome. A
      dissection 'entry' localized in the aortic arch or the descending aorta may
      increase the risk for postoperative stroke. Intraoperatively, cannulation of the
      femoral artery and extension of the LBI time over 45 min should be avoided.
      Especially in patients with manifest preoperative cerebral and/or end-organ
      malperfusion, the cannulation modality as well as the entire neuroprotective
      management should be chosen individually, respecting its limitations.

PMID- 22864790
TI  - Consistently lower narcotics consumption after video-assisted thoracoscopic
      surgery for early stage non-small cell lung cancer when compared to open surgery:
      a one-year follow-up study.
AB  - OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) is possibly associated
      with reduced acute pain and narcotics consumption when compared to open surgery,
      but little is known about the long-term effect. The goal of our study was to
      evaluate whether narcotics consumption is consistently lower after VATS for early
      stage non-small cell lung cancer (NSCLC), as compared to open surgery, during one
      year follow-up. METHODS: This nationwide retrospective cohort study was conducted
      using data relating to cancer registry and national compulsory comprehensive
      claims in Taiwan. Our study cases were those newly diagnosed with clinical Stage
      I NSCLC, who underwent primary lung resection in the year 2007. The date of the
      admission during which index surgery was performed was used as the index date. We
      compared the use of narcotics, between the VATS and open surgery groups, over a
      period of one year following the index date. We defined narcotics as either Level
      1 or 2 drugs as regulated in Taiwan. We also used an equiananalgesic dose chart
      to convert drug consumption into a uniform narcotics equivalent dose. Chi-square
      and t-tests were used for statistical analysis. RESULTS: We identified 329 cases
      (114 for VATS and 215 for open surgery). These two groups were balanced for most
      clinical variables. VATS was associated with lower narcotics consumption during
      the index admission (mean equivalent dose of intravenous morphine: 54.6 vs 71.4
      mg) and this trend extended to the period covering the 2nd to 12th month after
      index date (73.8 vs 149.5mg). CONCLUSIONS: Narcotics consumption is consistently
      lower after VATS for early stage NSCLC, as compared to open surgery. Further
      prospective studies would be of great value in validating this finding.

PMID- 22864791
TI  - Prognostic impact of intratumoural microvascular invasion and microlymphatic
      permeation on node-negative non-small-cell lung cancer: which indicator is the
      stronger prognostic factor?
AB  - OBJECTIVES: Microvascular invasion and microlymphatic permeation are indicators
      of microscopic tumour invasion into small vessels and have been considered to be
      powerful prognostic indicators for non-small-cell lung cancer (NSCLC). Several
      studies have suggested that these should be included in the TNM classification,
      but, there have been conflicting results regarding the prognostic impact of
      microvascular invasion and microlymphatic permeation. The aim of the current
      study was to clarify the prognostic impact of microvascular invasion and
      microlymphatic permeation on resected node-negative NSCLC by comparative
      analyses. METHODS: We reviewed the data of 1039 consecutive patients with
      pathological size-based stage T1a-3N0M0 NSCLC who underwent lobectomy or greater
      resection between 1993 and 2005. The median follow-up period was 108 months.
      Microvascular invasion and microlymphatic permeation were identified by the
      Victoria blue-van Gieson staining. The overall survival was then analysed.
      RESULTS: Microvascular invasion and microlymphatic permeation were observed in
      358 (34.5%) and 205 (19.7%) of patients, respectively. Both microvascular
      invasion and microlymphatic permeation were more prevalent in non-adenocarcinoma
      and larger-sized tumours. The 5-year overall survival rate of the microvascular
      invasion-positive group and microlymphatic permeation-positive group were 69.2
      and 84.6%, respectively, and the difference was statistically significant (P =
      0.002). On multivariate analyses, microvascular invasion, but not microlymphatic
      permeation, was an independent prognostic factor (microvascular invasion, hazard
      ratio [HR] 1.648, P = 0.001; microlymphatic permeation, HR 1.138, P = 0.588). The
      5-year overall survival rate of either the microvascular invasion- or
      microlymphatic permeation-positive T1a-b group was significantly lower than that
      of the corresponding double-negative (dn) T1a-b group (dnT1a-b, 93.7%;
      microvascular invasion-positive T1a-b, 85.2%, P < 0.001; microlymphatic
      permeation-positive T1a-b, 85.4%, P = 0.014), and overlapped to that of the dnT2a
      group (84.8%). However, in the T2a-b group, only microvascular invasion-positive
      T2a-b patients showed significantly lower overall survival than dnT2a-b patients,
      and their overall survival overlapped that of dnT3 patients (dn T2a-b, 83.5%;
      microvascular invasion-positive T2a-b, 60.6%, P < 0.001; dnT3, 53.8%; P = 0.316).
      The 5-year overall survival of microlymphatic permeation-positive T2a-b patients
      (86.2%) did not statistically differ from that of dnT2a-b patients (P = 0.856).
      CONCLUSIONS: Microvascular invasion and microlymphatic permeation have different
      impact on survival, and microvascular invasion rather than microlymphatic
      permeation is a strong prognostic factor in resected node-negative NSCLC.
      Microvascular invasion and microlymphatic permeation should be examined
      separately by elastic staining.

PMID- 22864792
TI  - Surgery for ruptured sinus of Valsalva aneurysm: 25-year experience with 55
      patients.
AB  - OBJECTIVES: Different surgical strategies have been evolved for the surgical
      treatment of ruptured sinus of Valsalva aneurysm (RSVA) from simple primary
      closure to patching of the rupture site by a dual chamber approach. We reviewed
      our 25-year experience and current literature regarding the efficacy of different
      surgical approaches. METHODS: A retrospective review identified 55 patients who
      underwent RSVA repair between 1985 and 2011. The mean age was 30.9 +/- 12.1
      years. The RSVA originated from the right coronary sinus in 43 patients (78.2%),
      from the non-coronary sinus in 11 (20.0%) and from the left in 1. Rupture into
      the right ventricle was the most common result (n = 38). Dual-chamber exposure
      (the involved chamber and aorta) was used in 67.3% of the patients and isolated
      trans-aortic approach was used in 32.7%. RSVA was repaired with either a patch (n
      = 43) or direct sutures (n = 12), whereas the aortic valve was replaced in eight
      patients among the last group. RESULTS: The hospital mortality rate was 3.6%. The
      follow-up was available in 94.3% (50 patients) of survivors ranging from 1 month
      to 25 years (mean 15.3 +/- 4.1 years). There were five late deaths. Recurrence of
      the fistula was seen in two primarily repaired (two of four patients) and none of
      the patched-closed patients. Actual survival was 93.4 +/- 3.7% at 10 years and
      87.1 +/- 5.6% at 15 years. Freedom from reoperations was 81.6 +/- 6.1% at 15
      years. CONCLUSIONS: Surgical treatment for RSVA carries an acceptably low
      operative risk and long-term freedom from death and reoperation. Surgical
      approach must be chosen according to the ruptured chamber and associated lesions.
      Patch repair of RSVA must be preferred.

PMID- 22864794
TI  - Reaching families at their homes for an intervention to reduce tobacco smoke
      exposure among infants.
AB  - The methods of reaching families for a home intervention trial (HIT) were
      analyzed in this study. The study aimed to reduce environmental tobacco smoke
      exposure among infants in one region of Germany. The systematic screening data of
      smoking among families in their homes were compared with reference data of a
      representative household sample of the state in which the study was conducted.
      The characteristics of participating and non-participating families were
      analyzed. All households (N = 3,570) containing at least one infant age 3 years
      or younger were selected using the residents' registration files and invited to
      participate in a screening assessment. Among these families, 3,293 (92.2 %) were
      contacted and from that group, 2,641 families participated in the screening.
      Compared with the reference sample, the screened sample included a higher
      proportion of families with employment and with more than 10 years of education.
      Participation in the HIT was recommended if at least one parent reported smoking
      one or more cigarettes per day during the previous 4 weeks. Among the 1,282
      families that met the inclusion criteria, 71.5 % took part in the screening.
      Participating families, compared with non-participating families, were older,
      included more families with two parents living in the household, and had higher
      rates of employment. The effect size of the final regression model was small
      (Cohen's f (2) = 0.01). In conclusion, proactive approaches that are delivered at
      home may yield a high reach of the target population and particularly of
      socioeconomically disadvantaged populations.

PMID- 22864793
TI  - The longevity effect of cranberry extract in Caenorhabditis elegans is modulated
      by daf-16 and osr-1.
AB  - Nutraceuticals are known to have numerous health and disease preventing
      properties. Recent studies suggest that extracts containing cranberry may have
      anti-aging benefits. However, little is known about whether and how cranberry by
      itself promotes longevity and healthspan in any organism. Here we examined the
      effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis
      elegans. Supplementation of the diet with cranberry extract (CBE) increased the
      lifespan in C. elegans in a concentration-dependent manner. Cranberry also
      increased tolerance of C. elegans to heat shock, but not to oxidative stress or
      ultraviolet irradiation. In addition, we tested the effect of cranberry on brood
      size and motility and found that cranberry did not influence these behaviors. Our
      mechanistic studies indicated that lifespan extension induced by CBE requires the
      insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes
      longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream
      effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase
      pathway. However, SIR-2.1 and JNK signaling pathways are not required for
      cranberry to promote longevity. Our findings suggest that cranberry
      supplementation confers increased longevity and stress resistance in C. elegans
      through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging
      property of widely consumed cranberry and elucidates the underpinning mechanisms.

PMID- 22864795
TI  - Modified total en bloc spondylectomy for thoracolumbar spinal tumors via a single
      posterior approach.
AB  - PURPOSE: The objectives of this study were to describe our surgical management
      with a modified total en bloc spondylectomy (TES) and to evaluate the clinical
      effects in patients with thoracolumbar tumors. METHODS: Sixteen consecutive
      patients with thoracolumbar neoplasms underwent a modified TES via single
      posterior approach followed by dorsoventral reconstruction from December 2008 to
      July 2011. Details of the modified technique were described and the patients'
      clinical information was retrospectively reviewed and analyzed. RESULTS:
      Significant improvements in neurological function were achieved in most of the
      patients. Local pain or radicular leg pain was relieved postoperatively. The mean
      operation time was 7.2 h, with an average blood loss of 2,300 ml. No major
      complications, instrumentation failure or local recurrence was found at the final
      follow-up. Five patients died of the disease during mean 14-month (3.0-23) follow
      up. CONCLUSIONS: The modified TES with a single posterior approach is feasible,
      safe and effective for thoracolumbar spine tumors.

PMID- 22864796
TI  - Zef is one of my medical heroes, a man who made a major contribution to the
      health of children around the world.

PMID- 22864797
TI  - Prognostic significance of cyclin D1, beta-catenin, and MTA1 in patients with
      invasive ductal carcinoma of the breast.
AB  - BACKGROUND: To investigate markers for predicting breast cancer progression, we
      performed a candidate gene-based study that assessed expression change of three
      genes, cyclin D1, beta-catenin, and metastasis-associated protein-1 (MTA1),
      involving in aggressive phenotypes of cancerous cells, namely hyperproliferation,
      epithelial-mesenchymal transition, and global transcriptional regulation.
      METHODS: Specimens were from 150 enrolled female patients, with invasive ductal
      carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, beta
      catenin, and MTA1 in cancerous and noncancerous cells microdissected from the
      primary tumor site was determined by quantitative real-time PCR. The relationship
      between mRNA expression levels of the genes and clinicopathologic features was
      assessed by statistical analysis. Disease-free and overall survival (DFS and OS)
      were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox
      regression model. RESULTS: Cyclin D1 was shown to be overexpressed in late-stage
      breast cancer (stage III/IV). Breast cancer with lymph node metastasis (LNM)
      showed significantly higher frequency of overexpressed cyclin D1, beta-catenin,
      and MTA1 (P < 0.05). Patients carrying greater numbers of overexpressed genes had
      joint effects on increased risk in tumors of advanced stages (P ( trend ) = 0.03)
      and LNM (P ( trend ) < 0.01). In the LNM-negative group, patients whose tumors
      with greater number of cyclin D1, beta-catenin, and MTA1 overexpressions were
      associated with poorer clinical outcomes, with hazard ratio of 14.79 for OS (P =
      0.015) and 7.54 for DFS (P = 0.015) using multivariate Cox regression analysis
      during the 10-year follow-up. CONCLUSIONS: Higher expression of cyclin D1, beta
      catenin, and MTA1 mRNAs in breast cancers may prove effective in predicting
      unfavorable outcomes of breast cancer.

PMID- 22864798
TI  - The unique clinical characteristics of melanoma diagnosed in children.
AB  - BACKGROUND: Studies have demonstrated a higher rate of nodal metastases in
      melanoma of childhood, but there is controversy about the overall prognosis
      relative to adults. We describe a large single-institution experience with
      pediatric melanoma and assess prognostic characteristics. METHODS: Retrospective
      review identified 126 patients diagnosed with melanoma at <21 years of age and
      referred for treatment from 1986 to 2011. Atypical lesions were excluded.
      Clinicopathologic characteristics were correlated with sentinel lymph node (SLN)
      status and outcomes. RESULTS: SLN biopsy was positive in 18 of 62 cases (29 %).
      Increasing Breslow thickness correlated with a positive SLN (p < 0.05). After a
      median follow-up of 5 years, there were 27 recurrences and 20 deaths. Positive
      SLN patients had significantly worse recurrence-free survival (RFS, p < 0.05) and
      significantly worse melanoma-specific survival (MSS, p = 0.05) compared with
      negative SLN patients. The 5-year RFS and MSS for positive SLN patients were 59.5
      and 77.8 %, compared with 93.7 and 96.8 % for negative SLN patients. Recurrences
      and melanoma-related deaths were often seen beyond 5 years. No deaths have
      occurred in patients <12 years, but 9.1 % of patients 12-17 years and 17.2 % of
      patients 18-20 years died from melanoma (p = 0.291). CONCLUSIONS: Children with
      melanoma have higher rates of SLN metastases (29 %) than adults with comparable
      melanomas. Despite the higher incidence of nodal metastases, survival is equal to
      or better than what is reported for adults. However, long-term follow-up is
      necessary in this population since recurrences and deaths are often seen beyond 5
      years.

PMID- 22864799
TI  - Resolution of diabetes after pancreaticoduodenectomy in patients with and without
      pancreatic ductal cell adenocarcinoma.
AB  - BACKGROUND: New-onset diabetes mellitus (DM) is associated with pancreatic ductal
      cell adenocarcinoma (PDCA) and can resolve after pancreaticoduodenectomy (PD).
      Whether DM also resolves after PD in patients operated for disease other than
      PDCA remains to be determined. METHODS: We compared glycemic status before and
      after PD between patients with and without PDCA by review of a prospectively
      maintained database including all patients receiving PD from 2005 to 2011. New
      onset DM was defined as diagnosis of DM less than 24 months before PD, and cases
      with DM diagnosis>=24 months preceding PD were described as long-standing DM.
      RESULTS: Of 458 patients receiving PD, there were 146 (31.9%) PDCA and 312
      (68.1%) non-PDCA, including 160 benign diseases, 113 ampulla cancer, 29 distal
      common bile duct cancer, and 10 duodenal cancer. Overall prevalence of DM was
      higher in PDCA group than non-PDCA group (37.7 vs. 25.6%; P=0.011). Resolution of
      new-onset DM after PD was observed in 9 (41%) of 22 patients with PDCA and in 12
      (63%) of 19 patients without PDCA. Resolution of long-standing DM after PD was
      also observed in 3 (9.1%) of 33 patients with PDCA and in 6 (9.8%) of 61 patients
      without PDCA. CONCLUSIONS: DM resolved after PD in some patients both with and
      without PDCA. These findings suggest that PD-associated anatomic change may play
      a role in resolution of DM after PD.

PMID- 22864802
TI  - Abstracts of the oral presentations from the 37th Annual IUGA (International
      Urogynecological Association) Meeting. Brisbane, Australia. September 4-8, 2012.

PMID- 22864801
TI  - Artificial food colors and attention-deficit/hyperactivity symptoms: conclusions
      to dye for.
AB  - The effect of artificial food colors (AFCs) on child behavior has been studied
      for more than 35 years, with accumulating evidence from imperfect studies. This
      article summarizes the history of this controversial topic and testimony to the
      2011 Food and Drug Administration Food Advisory Committee convened to evaluate
      the current status of evidence regarding attention-deficit/hyperactivity disorder
      (ADHD). Features of ADHD relevant to understanding the AFC literature are
      explained: ADHD is a quantitative diagnosis, like hypertension, and some
      individuals near the threshold may be pushed over it by a small symptom
      increment. The chronicity and pervasiveness make caregiver ratings the most valid
      measure, albeit subjective. Flaws in many studies include nonstandardized
      diagnosis, questionable sample selection, imperfect blinding, and nonstandardized
      outcome measures. Recent data suggest a small but significant deleterious effect
      of AFCs on children's behavior that is not confined to those with diagnosable
      ADHD. AFCs appear to be more of a public health problem than an ADHD problem.
      AFCs are not a major cause of ADHD per se, but seem to affect children regardless
      of whether or not they have ADHD, and they may have an aggregated effect on
      classroom climate if most children in the class suffer a small behavioral
      decrement with additive or synergistic effects. Possible biological mechanisms
      with published evidence include the effects on nutrient levels, genetic
      vulnerability, and changes in electroencephalographic beta-band power. A table
      clarifying the Food and Drug Administration and international naming systems for
      AFCs, with cross-referencing, is provided.

PMID- 22864800
TI  - Molecular regulation of lymphangiogenesis in development and tumor
      microenvironment.
AB  - A rapid progress has been made in the field of lymphatic research during the last
      15 years. This includes better understanding of the cellular events and molecular
      players involved in the lymphatic vessel formation and remodeling in development.
      The key players identified in developmental lymphangiogenesis, including vascular
      endothelial cell growth factor-C (VEGF-C) / VEGFR-3 and angiopoietins (ANGPTs)/
      TIE pathways, are also crucial for pathological lymphatic vessel growth. In solid
      tumor, tumor cells as well as tumor-associated stromal cells, such as tumor
      infiltrating leukocytes, contribute to intra- and peri-tumoral lymphangiogenesis
      via secreting lymphangiogenic growth factors. Tumor-associated lymphatic
      endothelial cells also interact actively with tumor cells and leukocytes via
      secreting various chemokines. It has been well established that tumor
      lymphangiogenesis promotes tumor cell dissemination to regional lymph nodes. Thus
      manipulation of lymphangiogenic microenvironment could become another valuable
      approach in the combat of tumor progression.

PMID- 22864803
TI  - The abundance and diversity of legume-nodulating rhizobia in 28-year-old
      plantations of tropical, subtropical, and exotic tree species: a case study from
      the Forest Reserve of Bandia, Senegal.
AB  - Several fast-growing and multipurpose tree species have been widely used in West
      Africa to both reverse the tendency of land degradation and restore soil
      productivity. Although beneficial effects have been reported on soil
      stabilization, there still remains a lack of information about their impact on
      soil microorganisms. Our investigation has been carried out in exotic and native
      tree plantations of 28 years and aimed to survey and compare the abundance and
      genetic diversity of natural legume-nodulating rhizobia (LNR). The study of LNR
      is supported by the phylogenetic analysis which clustered the isolates into three
      genera: Bradyrhizobium, Mesorhizobium, and Sinorhizobium. The results showed
      close positive correlations between the sizes of LNR populations estimated both
      in the dry and rainy seasons and the presence of legume tree hosts. There were
      significant increases in Rhizobium spp. population densities in response to
      planting with Acacia spp., and high genetic diversities and richness of genotypes
      were fittest in these tree plantations. This suggests that enrichment of soil
      Rhizobium spp. populations is host specific. The results indicated also that
      species of genera Mesorhizobium and Sinorhizobium were lacking in plantations of
      non-host species. By contrast, there was a widespread distribution of
      Bradyrhizobium spp. strains across the tree plantations, with no evident
      specialization in regard to plantation type. Finally, the study provides
      information about the LNR communities associated with a range of old tree
      plantations and some aspects of their relationships to soil factors, which may
      facilitate the management of man-made forest systems that target ecosystem
      rehabilitation and preservation of soil biota.

PMID- 22864804
TI  - Excess body weight and second primary cancer risk after breast cancer: a
      systematic review and meta-analysis of prospective studies.
AB  - Several observational studies have investigated the role of body mass index (BMI)
      in second primary cancer incidence in women with breast cancer. We conducted a
      systematic review and meta-analysis of the evidence to assess the strength of
      this association. PubMed and Embase were searched for observational studies up to
      May 2012, and the reference lists of studies included in the analysis were
      examined. Random effects models were used to estimate summary relative risks
      (RRs) and 95 % confidence intervals (CIs). Thirteen prospective studies, five
      cohort and eight nested case-control studies, were included. In categorical meta
      analyses of BMI, obesity was associated to significantly increased risks of
      contralateral breast (RR = 1.37, 95 % CI: 1.20-1.57), breast (RR = 1.40, 95 % CI:
      1.24-1.58), endometrial (RR = 1.96, 95 % CI: 1.43-2.70), and colorectal (RR =
      1.89, 95 % CI: 1.28-2.79) second primary cancers. For a BMI increase of 5
      kg/m(2), dose-response meta-analyses resulted in significantly increased RRs of
      1.12 (95 % CI: 1.06-1.20) and 1.14 (95 % CI: 1.07-1.21) for contralateral breast
      and breast second primary cancers, respectively. The summary RR for endometrial
      second primary cancers was 1.46 (95 % CI: 1.17-1.83) for a 5-unit increment. This
      result emphasizes the importance of prevention policies aiming to reduce
      overweight and obesity prevalence. Clinical trials in breast cancer patients with
      excess body weight evaluating the effect of normal weight restoration on second
      primary cancer incidence are needed.

PMID- 22864805
TI  - The chronic gastrointestinal consequences associated with campylobacter.
AB  - Campylobacteriosis is a leading cause of acute infectious diarrhea in the
      developing world, where it causes considerable mortality, and in developed
      countries, where it accounts for significant healthcare and other costs. Evidence
      has emerged from basic science, clinical, and epidemiological domains that
      suggests that Campylobacter infection is not limited to acute illness but is also
      involved in the development of well-described extraintestinal sequelae, such as
      the Guillain-Barre syndrome and reactive arthritis, and may also contribute to
      the pathogenesis of chronic gastrointestinal conditions. This review will focus
      on the role of Campylobacter infection as a risk factor for the development of
      chronic gastrointestinal sequelae, such as functional gastrointestinal disorders,
      with which irritable bowel syndrome has been most frequently associated,
      inflammatory bowel disease, and celiac disease.

PMID- 22864806
TI  - Familial colon cancer syndromes: an update of a rapidly evolving field.
AB  - Colorectal cancer (CRC) is a major cause of morbidity and mortality in the world.
      Up to 30 % of CRCs have evidence of a familial component, and about 5 % are
      thought to be due to well-characterized inherited mutations. This review will
      focus on recent developments in the understanding of the individual hereditary
      CRC syndromes, including Lynch syndrome, familial CRC type X, familial
      adenomatous polyposis, MutYH-associated polyposis, Peutz-Jeghers syndrome,
      juvenile polyposis syndrome, PTEN hamartomatous syndrome, and serrated polyposis
      syndrome. Advances within the area of hereditary colon cancer syndromes paint a
      picture of a rapidly moving, rapidly maturing, and increasingly collaborative
      field with many opportunities for ongoing research and development.

PMID- 22864807
TI  - [Compliance of patients concerning recommended radiotherapy in breast cancer : 
      Association with recurrence, age, and hormonal therapy].
AB  - BACKGROUND AND PURPOSE: In this study, we investigated how often guidelines for
      radiation therapy in patients with breast cancer are not complied with, which
      patient group is mostly affected, and how this influences local recurrence.
      PATIENTS AND METHODS: All patients (n = 1,903) diagnosed between November 2003
      and December 2008 with primary invasive or intraductal breast cancer in the
      interdisciplinary breast center of the Charite Hospital Berlin were included and
      followed for a median 2.18 years. RESULTS: Patients who, in contrast to the
      recommendation of the interdisciplinary tumor board, did not undergo
      postoperative radiation experienced a fivefold higher local recurrence rate (p <
      0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5%
      in this group. The 5-year locoregional recurrence-free survival of patients
      following the recommendations was 93.3%. Guideline compliance was dependent on
      age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and
      increased diameter of the primary tumor. Multiple logistic regression analysis
      showed an association between compliance and age or hormonal therapy. CONCLUSION:
      In order to avoid local recurrence patients should be motivated to comply with
      guideline driven therapy. Since a higher number of local recurrences is observed
      in health services research compared to clinical research, studies on the value
      of adjuvant treatment following local recurrence should be performed.

PMID- 22864808
TI  - A novel model to predict O-glycosylation sites using a highly unbalanced dataset.
AB  - In silico approaches have become an alternative method to study O-glycosylation.
      In this paper, we developed a linear interpretable model for O-glycosylation
      prediction based on an unbalanced dataset, analyzing the underlying biological
      knowledge of glycosylation. A training set of 4446 sites involving 468 positive
      sites and 3978 negative sites was developed during this research. The sites were
      encoded using the amino acid index (AAindex), and the forward stepwise procedure
      utilized for feature selection. The linear discriminant analysis with an equal a
      priori probability (PP-LDA) was employed to develop the interpretable model.
      Performance of the model was verified using both the internal leave-one-out cross
      validation and external validation methods. Two non-linear algorithms, the
      supervised support vector machine and the unsupervised self-organizing
      competitive neural network, were used as comparisons. The PP-LDA model exhibited
      improved classification results with accuracy of 82.1% for cross-validations and
      80.3% for external prediction. Further analysis of this linear model indicated
      that the properties at position R(1) and the properties relative to
      hydrophobicity contributed more to the glycosylation prediction. However, the
      alpha and turn propensities at the C-terminal, together with physicochemical
      properties at the N-terminal, are also relative to the glycosylation activity.
      This model is not only capable of predicting the possibility of glycosylation
      using an unbalanced dataset, but is also helpful to understand the underlying
      biological mechanisms of glycosylation. Considering the publicly accessibility of
      our prediction model, a downloadable program is provided in our supply materials.

PMID- 22864809
TI  - Medicinal parasitic plants on diverse hosts with their usages and barcodes.
AB  - Medicinal properties of parasitic plants were investigated by means of
      ethnobotanical study in some areas of northeastern Thailand. Important
      traditional usages are: Scurrula atropurpurea nourishes blood, Dendrophthoe
      pentandra decreases high blood pressure, and Helixanthera parasitica treats liver
      disease. Their systematics were also determined. The research is based on
      findings obtained from 100 parasite-host pairs. Of these, eight parasitic species
      were recorded; they are members of two families, viz. family Loranthaceae, namely
      D. lanosa, D. pentandra, H. parasitica, Macrosolen brandisianus, M.
      cochinchinensis and S. atropurpurea, and family Viscaceae, namely Viscum
      articulatum and V. ovalifolium. In addition, each parasitic species is found on
      diverse hosts, indicating non-host-parasitic specificity. Species-specific
      tagging of all species studied was carried out using the rbcL and psbA-trnH
      chloroplast regions. These tag sequences are submitted to GenBank databases under
      accession numbers JN687563-JN687578. Genetic distances calculated from nucleotide
      variations in a couple of species of each genus, Dendrophthoe, Macrosolen, and
      Viscum, were 0.032, 0.067 and 0.036 in the rbcL region, and 0.269, 0.073 and
      0.264 in the psbA-trnH spacer region, respectively. These variations will be used
      for further identification of incomplete plant parts or other forms such as
      capsule, powder, dried or chopped pieces.

PMID- 22864810
TI  - Risedronate-associated scleritis: a case report and review of the literature.
AB  - This paper presents the first reported case of risedronate-associated scleritis
      and conducts a review of bisphosphonates and inflammatory eye diseases. A case of
      scleritis associated with risedronate use in a 73-year-old Chinese woman is
      reported. The English medical literature was reviewed for bisphosphonates and
      their association with inflammatory eye diseases. Cases of ocular inflammation in
      patients taking bisphosphonates have been reported since the early 1990s.
      Reported cases include both nitrogen- and non-nitrogen-containing bisphosphonates
      and with both intravenous and oral use. We report the first case of risedronate
      induced scleritis. The case involves a 73-year-old woman who developed scleritis
      following exposure to risedronate in 2007 with recurrence of scleritis upon
      risedronate exposure again in 2009. Discontinuation of risedronate and treatment
      with intravenous and topical corticosteroids resulted in both clinical and
      radiological improvements within 24 h. Applying Naranjo's adverse drug reaction
      probability scale, a causality assessment was made which categorized this
      reaction as definite with a score of 9. In our case, there was a strong causal
      relationship between the use of risedronate and scleritis. Although rare, ocular
      adverse effects of bisphosphonates may be serious and should be made known to
      prescribing physicians. This is important in the practice of rheumatology as many
      of the patients are prescribed this class of medication for either prevention or
      treatment of osteoporosis. Moreover, ocular inflammation can be a sign of
      systemic disease, and such patients may be referred to a rheumatologist.

PMID- 22864811
TI  - Serial interferon-gamma release assays for screening and monitoring of
      tuberculosis infection during treatment with biologic agents.
AB  - Screening for latent tuberculosis infection (LTBI) prior to the prescribing of
      anti-TNF agents and monitoring for infection during treatment are recommended.
      The feasibility of novel screening tools, including QuantiFERON-TB Gold In-Tube
      (QFT-GIT), remains unclear in the setting of immunosuppression. The aim of this
      study was to evaluate the usefulness of serial QFT-GIT during biologic therapy to
      assess whether dynamic changes in IFN-gamma levels may be helpful in identifying
      reactivation of LTBI or newly acquired TB. We conducted a prospective study on
      patient candidates to TNF inhibitors. QFT-GIT was performed at baseline and after
      3 and 6 months since biologic onset. A further follow-up period of 6 months was
      observed. Among patients enrolled (n = 119; F = 69 %; median age = 47 years,
      range 18-80), 24 had at least 1 risk factor for LTBI. Ninety-six were taking
      immunosuppressants at the time of TB testing. At baseline, 5 patients displayed
      positive, 93 negative, and 21 indeterminate QFT-GIT results. We observed QFT-GIT
      conversions and reversions in 12 patients with LTBI and in 73 without LTBI. QFT
      GIT results changed of 28 % at month 3 and of 21 % at month 6; the greatest
      change was observed in patients with indeterminate results that became negative
      (15 %; p < 0.02). No TB cases were detected. In conclusion, the routine use of
      both QFT-GIT and TST at screening seems not to give any advantage in the setting
      of patients awaiting biologics. In addition, the feasibility of serial QFT-GIT
      during biologic therapy needs definition since changes in IFN-gamma levels may
      occur without a pathologic connotation.

PMID- 22864813
TI  - Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem,
      region-matched assessment of plaques.
AB  - The definitive Alzheimer's disease (AD) diagnosis requires postmortem
      confirmation of neuropathological hallmarks-amyloid-beta (Abeta) plaques and
      neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging
      presents an opportunity to investigate amyloid deposition in vivo. The (11)C
      Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date;
      however, regional variations in (11)C-PiB binding and the extent of agreement
      with neuropathological assessment have not been thoroughly investigated. Sojkova
      and colleagues [35] reported variable agreement between CERAD-based
      neuropathologic diagnosis of AD lesions and mean cortical PiB, suggesting the
      need for a more direct quantification of regional Abeta in relation to in vivo
      imaging. In the present study, we extend these findings by examining the
      correspondence among regional (11)C-PiB load, region-matched quantitative
      immunohistological assessments of Abeta and NFTs, and brain atrophy (MRI) in six
      older Baltimore Longitudinal Study of Aging participants who came to autopsy
      (imaging-autopsy interval range 0.2-2.4 years). The total number of Abeta plaques
      (6E10) and NFTs (PHF1) in paraffin sections from hippocampus, orbito-frontal
      cortex, anterior and posterior cingulate gyrus, precuneus and cerebellum was
      quantified using a technique guided by unbiased stereological principles. We
      report a general agreement between the regional measures of amyloid obtained via
      stereological assessment and imaging, with significant relationships evident for
      the anterior (r = 0.83; p = 0.04) and posterior (r = 0.94; p = 0.005) cingulate
      gyri, and the precuneus (r = 0.94; p = 0.005). No associations were observed
      between (11)C-PiB load and NFT count for any of the regions examined (p > 0.2 in
      all regions), or between regional Abeta or NFT counts and corresponding brain
      volumes. The strong associations of PiB retention with region-matched,
      quantitative analyses of Abeta in postmortem tissue offer support for the
      validity of (11)C-PiB-PET imaging as a method for evaluation of plaque burden in
      vivo.

PMID- 22864814
TI  - Selection of novel reference genes for use in the human central nervous system: a
      BrainNet Europe Study.
AB  - The use of an appropriate reference gene to ensure accurate normalisation is
      crucial for the correct quantification of gene expression using qPCR assays and
      RNA arrays. The main criterion for a gene to qualify as a reference gene is a
      stable expression across various cell types and experimental settings. Several
      reference genes are commonly in use but more and more evidence reveals variations
      in their expression due to the presence of on-going neuropathological disease
      processes, raising doubts concerning their use. We conducted an analysis of
      genome-wide changes of gene expression in the human central nervous system (CNS)
      covering several neurological disorders and regions, including the spinal cord,
      and were able to identify a number of novel stable reference genes. We tested the
      stability of expression of eight novel (ATP5E, AARS, GAPVD1, CSNK2B, XPNPEP1,
      OSBP, NAT5 and DCTN2) and four more commonly used (BECN1, GAPDH, QARS and TUBB)
      reference genes in a smaller cohort using RT-qPCR. The most stable genes out of
      the 12 reference genes were tested as normaliser to validate increased levels of
      a target gene in CNS disease. We found that in human post-mortem tissue the novel
      reference genes, XPNPEP1 and AARS, were efficient in replicating microarray
      target gene expression levels and that XPNPEP1 was more efficient as a normaliser
      than BECN1, which has been shown to change in expression as a consequence of
      neuronal cell loss. We provide herein one more suitable novel reference gene,
      XPNPEP1, with no current neuroinflammatory or neurodegenerative associations that
      can be used for gene quantitative gene expression studies with human CNS post
      mortem tissue and also suggest a list of potential other candidates. These data
      also emphasise the importance of organ/tissue-specific stably expressed genes as
      reference genes for RNA studies.

PMID- 22864815
TI  - A combined approach identifies three mRNAs that are down-regulated by microRNA
      29b and promote invasion ability in the breast cancer cell line MCF-7.
AB  - BACKGROUND AND AIMS: MicroRNAs (miRNAs) are short noncoding RNAs that regulate
      gene expression by targeting mRNAs. Our previous study found that miR-29b
      strongly regulates the migration and invasion of breast cancer cells. Here, we
      aimed to identify the mRNAs targeted by miR-29b. METHODS: We used microarray
      experiments in conjunction with computational methods to identify the mRNAs that
      were most susceptible to miR-29b-mediated repression. We further confirmed the
      activities of three target genes, C1QTNF6, SPARC, and COL4A2, by luciferase
      reporter analyses and invasion assays. RESULTS: We evaluated the impact of miR
      29b on global mRNA expression in MCF-7 human breast cancer cells through
      microarray analysis and further analyzed four genes that were at least twofold
      down-regulated and predicted as miR-29b targets by at least two of the four
      widely used miRNA target prediction algorithms. We also analyzed one mRNA that
      was down-regulated by 1.8-fold but was predicted to have significant interactions
      with miR-29b in pathway analysis and was predicted as a miR-29b target by all
      four algorithms. Luciferase reporter and invasion assays revealed that C1QTNF6,
      SPARC, and COL4A2 were targeted by miR-29b and that the degradation of any one of
      these mRNAs could promote invasion in MCF-7 cells. CONCLUSIONS: C1QTNF6, SPARC,
      and COL4A2 are targeted by miR-29b, and the down-regulation of these three mRNAs
      can contribute to the invasion ability of MCF-7 cells.

PMID- 22864817
TI  - Three-dimensional echocardiographic evaluation of quadricuspid systemic
      atrioventricular valve.

PMID- 22864816
TI  - Non-platinum doublets were as effective as platinum-based doublets for
      chemotherapy-naive advanced non-small-cell lung cancer in the era of third
      generation agents.
AB  - PURPOSE: The aim was to compare the efficacy between doublets of third-generation
      agents (non-platinum) and doublets of platinum plus a third-generation agent
      (platinum-based) for chemotherapy-naive advanced non-small-cell lung cancer
      (NSCLC). METHODS: We conducted a literature-based meta-analysis to compare the
      efficacy between doublets of third-generation agents and doublets of platinum
      plus a third-generation agent for chemotherapy-naive advanced NSCLC. The primary
      end point was overall survival, and the secondary end points were progression
      free survival (PFS) and response rate. Subgroup analyses were also conducted by
      different non-platinum doublet regimens or different platinum-based doublets. A
      descriptive review for toxicity was performed. RESULTS: Sixteen randomized
      controlled trials were identified ultimately. Results demonstrated that the
      efficacy of non-platinum doublets was comparable with platinum-based doublets
      according to the overall survival (HR = 1.03, 95 % CI = 0.98-1.08, p = 0.29).
      Subgroup analyses by different non-platinum doublets also showed the efficacy of
      all the third-generation doublets, such as vinorelbine plus gemcitabine,
      vinorelbine plus paclitaxel, gemcitabine plus paclitaxel, and gemcitabine plus
      docetaxel, was comparable with platinum-based doublets (HR = 1.00, 95 % CI = 0.78
      1.27, p = 0.98; HR = 0.97, 95 % CI = 0.80-1.18, p = 0.79; HR = 1.05, 95 % CI =
      0.99-1.12, p = 0.11; HR = 1.01, 95 % CI = 0.92-1.10, p = 0.87; respectively).
      Subgroup analyses by different platinum-based doublets indicated that the
      efficacy of the third-generation doublets were equal to both cisplatin-based
      doublets and carboplatin-based doublets (HR = 1.08, 95 % CI = 1.00-1.17, p =
      0.05; HR = 1.00, 95 % CI = 0.94-1.05, p = 0.94; respectively). The secondary end
      points indicated that platinum-based doublets might have an advantage in PFS but
      not in response rate (HR = 1.06, 95 % CI = 1.01-1.12, p = 0.03; RR = 0.99, 95 %
      CI = 0.90-1.08, p = 0.81; respectively). CONCLUSIONS: Non-platinum doublets were
      as effective as platinum-based doublets with different toxicity profile for
      chemotherapy-naive advanced NSCLC in the era of third-generation agents.

PMID- 22864818
TI  - Roles of galectin-7 and S100A9 in cervical squamous carcinoma:
      Clinicopathological and in vitro evidence.
AB  - In our study, we for the first time assessed the association of galectin-7 and
      S100A9 with clinicopathological variables and survival outcomes in cervical
      squamous carcinoma patients and explored the underlying molecular mechanisms in
      cervical squamous carcinoma cell lines. Immunohistochemical analysis of 243
      patient samples showed that the positive staining rate for galectin-7 and S100A9
      gradually decreased from normal cervical tissue to intraepithelial neoplasia and
      to cervical squamous carcinoma. Both galectin-7 and S100A9 showed significant
      negative association with lymph node metastasis and staging of cervical squamous
      carcinoma. Cervical squamous carcinoma patients with negative staining of
      galectin-7 or S100A9 showed significantly lower 5-year overall survival rate than
      those with positive staining. Multivariate analysis with the Cox's proportional
      hazards model indicated that both galectin-7 and S100A9 had significant
      protective effect on cervical squamous carcinoma patients. Subsequent in vitro
      study in SiHa and C-33A human cervical squamous carcinoma cell lines revealed
      that knocking down galectin-7 or S100A9 enhanced tumor cell invasion and tumor
      cell viability against paclitaxel-induced apoptotic stress, likely through
      increasing the matrix metalloproteinase-9 expression and activating the
      phosphatidylinositol 3-kinase/Akt signaling pathway, respectively. Knocking down
      both galectin-7 and S100A9 produced a synergistic effect, with galectin-7
      displaying more significant and consistent protective effects than S100A9 on
      cervical squamous carcinoma cells. In summary, our study for the first time
      provides clinicopathological and in vitro evidence showing that both galectin-7
      and S100A9 play important protective roles in cervical squamous carcinoma, which
      provides fresh insights into the biology of cervical squamous carcinoma.

PMID- 22864819
TI  - Comment on: A commentary on changing infant death rates and a plea to use sudden
      infant death syndrome as a cause of death.

PMID- 22864820
TI  - An anomaly in U.S. SIDS data reported in the CDC wonder.cdc.gov mortality
      database.

PMID- 22864821
TI  - Hippocampal asymmetry and sudden unexpected death in infancy: a case report.
AB  - The differential diagnosis of known entities associated with sudden unexpected
      death in infancy is ever expanding. Here we report the case of a 10-month-old
      infant boy whose clinical presentation mimicked that of the sudden infant death
      syndrome (SIDS). This presentation included the typical features of SIDS: sleep
      related death; prone position upon discovery; and minor illness within 2 days of
      death. Nevertheless, neuropathologic examination revealed striking hippocampal
      asymmetry and microdysgenesis similar to that reported previously by us in
      toddlers with sleep-related sudden death. Hippocampal maldevelopment in the
      setting of sudden death in infants and toddlers is analogous to sudden unexpected
      death in epilepsy associated with temporal lobe pathology, and suggests a
      possible role for seizures in the terminal events leading to sudden death. This
      report serves to alert pediatric and forensic pathologists to hippocampal
      asymmetry and microdysgenesis in the differential diagnosis of sudden infant
      death mimicking SIDS.

PMID- 22864822
TI  - Alumoxane/ferroxane nanoparticles for the removal of viral pathogens: the
      importance of surface functionality to nanoparticle activity.
AB  - A bi-functional nano-composite coating has been created on a porous Nomex(r)
      fabric support as a trap for aspirated virus contaminated water. Nomex(r) fabric
      was successively dip-coated in solutions containing cysteic acid functionalized
      alumina (alumoxane) nanoparticles and cysteic acid functionalized iron oxide
      (ferroxane) nanoparticles to form a nanoparticle coated Nomex(r) (NPN) fabric.
      From SEM and EDX the nanoparticle coating of the Nomex(r) fibers is uniform,
      continuous, and conformal. The NPN was used as a filter for aspirated
      bacteriophage MS2 viruses using end-on filtration. All measurements were repeated
      to give statistical reliability. The NPN fabrics show a large decrease as
      compared to Nomex(r) alone or alumoxane coated Nomex(r). An increase in the
      ferroxane content results in an equivalent increase in virus retention. This
      suggests that it is the ferroxane that has an active role in deactivating and/or
      binding the virus. Heating the NPN to 160  degrees C results in the loss of
      cysteic acid functional groups (without loss of the iron nanoparticle's core
      structure) and the resulting fabric behaves similar to that of untreated
      Nomex(r), showing that the surface functionalization of the nanoparticles is
      vital for the surface collapse of aspirated water droplets and the absorption and
      immobilization of the MS2 viruses. Thus, for virus immobilization, it is not
      sufficient to have iron oxide nanoparticles per se, but the surface functionality
      of a nanoparticle is vitally important in ensuring efficacy.

PMID- 22864823
TI  - Piezoelectric substrates promote neurite growth in rat spinal cord neurons.
AB  - We tested the possibility that exogenous electrical activity from a piezoelectric
      substrate could influence neuronal structure in cultured spinal cord neurons.
      Oscillating electrical fields were delivered to rat neurons via substrates
      consisting of poly(vinylidene fluoride) film, both in its piezoelectric (PZ) and
      non-piezoelectric (PV) forms. To induce oscillating electrical fields at the film
      surfaces, a 50 Hz mechanical vibration was applied. After 4 days of mechano
      electrical stimulation, neuronal densities were increased by 115% and neurons
      grew 79% more neurites, with more than double the branch points, compared with
      neurons grown on non-stimulated PZ films (p < 0.001). The effects were due to
      electrical field, because vibration applied to non-PZ films did not increase
      neurite growth. We conclude that the oscillating electric fields produced from PZ
      polymer substrates can induce plastic changes in neurons of the central nervous
      system and herein we show its influence on neurite growth and branching.

PMID- 22864824
TI  - Biomechanical assessment of the individual risk of rupture of cerebral aneurysms:
      a proof of concept.
AB  - This study is a step towards a new biomechanical-based measurement of the patient
      specific risk of rupture of cerebral aneurysms. Following a previous experimental
      investigation suggesting a correlation between the risk of rupture and the
      material properties of cerebral aneurysms, fluid-structure interaction
      simulations are performed to compare the deformations of a patient-specific
      aneurysm when using degraded or undegraded materials. Results show that material
      properties have a major impact on the magnitude of systolic/diastolic aneurysmal
      volume variations along the cardiac cycle. Changes in terms of aneurysmal volume
      variations depending on the tissue characteristics are shown to be measurable by
      medical imaging. A one-at-a-time data uncertainty analysis is also presented and
      shows the robustness of this result to input data uncertainties. The study thus
      suggests that aneurysmal volume variations may be used as the basis of a
      biomechanical index of rupture risk.

PMID- 22864825
TI  - Photoluminescence from Bi5(GaCl4)3 molecular crystal.
AB  - Bi(5)(GaCl(4))(3) sample has been synthesized through the oxidation of Bi metal
      by gallium chloride (GaCl(3)) salt. Powder X-ray diffraction as well as micro
      Raman scattering results revealed that, in addition to crystalline
      Bi(5)(GaCl(4))(3) in the product, an amorphous phase containing [GaCl(4)](-) and
      [Ga(2)Cl(7)](-) units also exists. The thorough comparison of steady-state and
      time-resolved photoluminescent behaviors between the Bi(5)(GaCl(4))(3) product
      and Bi(5)(AlCl(4))(3) crystal leads us to conclude that Bi(5)(3+) is the dominant
      emitter in the product, which gives rise to the ultrabroad emission ranging from
      1 to 2.7 MUm. Detailed quantum chemistry calculation helps us assign the observed
      excitations to some electronic transitions of the Bi(5)(3+) polycation,
      especially at shorter wavelengths. It is believed that our work shown here is not
      only helpful to solve the confusions on the luminescent origin of bismuth in
      other material systems, but also serves to develop novel broadband tunable laser
      materials.

PMID- 22864826
TI  - Enantioselective supramolecular carriers for nucleoside drugs. A thermodynamic
      and kinetic gas phase investigation.
AB  - The enantioselective interactions between chiral tetra-amidic receptors and
      nucleosides have been investigated by the ESI-IT-MS and ESI-FT-ICR-MS
      methodologies. Configurational effects on the CID fragmentation of diastereomeric
      [M(H)(2)*H*A](+) aggregates (A = 2'-deoxycytidine dC, citarabine (ara-C) were
      found to be mostly offset by isotope effect in [S(X)(2)*H*A](+) (X = H, D)
      differently from the results obtained on the analogues (A = cytidine C and
      gemcitabine G). This result points the involvement of two different
      nucleoside/tetraamide isoforms. The structural differences of the
      [M(H)(2)*H*A](+) (A = C and G) complexes vs. the [M(H)(2)*H*A](+) (dC and ara-C)
      ones is fully confirmed by the kinetics of their uptake of the 2-aminobutane
      enantiomers, measured by FT-ICR mass spectrometry. Indeed, uptake of the 2
      aminobutane enantiomers by [M(H)(n)*H*A](+) (n = 1,2; A = dC and ara-C) complexes
      is reversible, while that by [M(H)(n)*H*A](+) (n = 1,2; A = C and G) is not. The
      most encouraging result concerning the measured fragmentation and kinetic
      differences between C and ara-C, that are just epimers, indicates the possibility
      to subtly modulate the non-covalent drug/receptor interactions, through the
      electronic properties of the 2'-substituent on the nucleoside furanose ring, and
      furthermore on its three-dimensional position.

PMID- 22864827
TI  - Consecutive fragmentation mechanisms of protonated ferulic acid probed by
      infrared multiple photon dissociation spectroscopy and electronic structure
      calculations.
AB  - Protonated ferulic acid and its principle fragment ion have been characterized
      using infrared multiple photon dissociation spectroscopy and electronic structure
      calculations at the B3LYP/6-311 + G(d,p) level of theory. Due to its extensively
      conjugated structure, protonated ferulic acid is observed to yield three stable
      fragment ions in IRMPD experiments. It is proposed that two parallel
      fragmentation pathways of protonated ferulic acid are being observed. The first
      pathway involves proton transfer, resulting in the loss of water and subsequently
      carbon monoxide, producing fragment ions m/z 177 and 149, respectively.
      Optimization of m/z 177 yields a species containing an acylium group, which is
      supported by a diagnostic peak in the IRMPD spectrum at 2168 cm(-1). The second
      pathway involves an alternate proton transfer leading to loss of methanol and
      rearrangement to a five-membered ring.

PMID- 22864828
TI  - Unusual complex formation and chemical reaction of haloacetate anion on the
      exterior surface of cucurbit[6]uril in the gas phase.
AB  - Noncovalent interactions of cucurbit[6]uril (CB[6]) with haloacetate and halide
      anions are investigated in the gas phase using electrospray ionization ion
      mobility mass spectrometry. Strong noncovalent interactions of monoiodoacetate,
      monobromoacetate, monochloroacetate, dichloroacetate, and trichloroacetate on the
      exterior surface of CB[6] are observed in the negative mode electrospray
      ionization mass spectra. The strong binding energy of the complex allows
      intramolecular S(N)2 reaction of haloacetate, which yields externally bound CB[6]
      halide complex, by collisional activation. Utilizing ion mobility technique,
      structures of exteriorly bound CB[6] complexes of haloacetate and halide anions
      are confirmed. Theoretically determined low energy structures using density
      functional theory (DFT) further support results from ion mobility studies. The
      DFT calculation reveals that the binding energy and conformation of haloacetate
      on the CB[6] surface affect the efficiency of the intramolecular S(N)2 reaction
      of haloacetate, which correlate well with the experimental observation.

PMID- 22864829
TI  - MALDI in-source decay mass spectrometry of polyamidoamine dendrimers.
AB  - We report using MALDI-ISD (in-source decay) mass spectrometry (MS) to
      characterize highly branched synthetic polymers of polyamidoamine (PAMAM)
      dendrimer. This inherently monodisperse polymer possesses dendritic branches
      networked by tertiary amines and an amide functionality in each repeating unit.
      Among various ISD matrices examined, 2,5-DHB was the most efficient, yielding 33
      fragments produced by single- or multiple-bond cleavages. Detailed analysis
      revealed that cleavages at tertiary amine sites (S- and E-type fragments) were
      the most pronounced, with various other cleavages around amide groups. The
      fragmentation mechanism appeared to follow the radical-induced dissociation
      pathway. In addition, the matrix dependence of PAMAM MALDI-ISD differed from that
      of peptides/proteins. The observed fragments provided rich structural
      information, which was suitable to characterize dendritic polymers.

PMID- 22864830
TI  - p38alpha MAP kinase phosphorylates RCAN1 and regulates its interaction with
      calcineurin.
AB  - RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a
      serine/threonine protein phosphatase that plays a critical role in many
      physiological processes. In this report, we demonstrate that p38alpha MAP kinase
      can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is
      a good protein substrate for calcineurin. In addition, we found that
      unphosphorylated RCAN1 noncompetitively inhibits calcineurin protein phosphatase
      activity and that the phosphorylation of RCAN1 by p38alpha MAP kinase decreases
      the binding affinity of RCAN1 for calcineurin. These findings reveal the
      molecular mechanism by which p38alpha MAP kinase regulates the function of
      RCAN1/calcineurin through phosphorylation.

PMID- 22864831
TI  - Progress in defining heterogeneity and modeling periglomerular cells in the
      olfactory bulb.
AB  - In recent years the evolution of olfactory bulb periglomerular cells, as well as
      the function of periglomerular cells in olfactory encoding, has attracted
      increasing attention. Studies of neural information encoding based on the
      analysis of simulation and modeling have given rise to electrophysiological
      models of periglomerular cells, which have an important role in the understanding
      of the biology of these cells. In this review we provide a brief introduction to
      the anatomy of the olfactory system and the cell types in the olfactory bulb. We
      elaborate on the latest progress in the study of the heterogeneity of
      periglomerular cells based on different classification criteria, such as
      molecular markers, structure, ion channels and action potentials. Then, we
      discuss the several existing electrophysiological models of periglomerular cells,
      and we highlight the problems and defects of these models. Finally, considering
      our present work, we propose a future direction for electrophysiological
      investigations of periglomerular cells and for the modeling of periglomerular
      cells and olfactory information encoding.

PMID- 22864832
TI  - Myeloid-specific expression of Stat3C results in conversion of bone marrow
      mesenchymal stem cells into alveolar type II epithelial cells in the lung.
AB  - Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate
      from the bone marrow, and influence each other in vivo. To elucidate the
      mechanism that controls the interrelationship between these two cell types, the
      signaling pathway of signal transducer and activator of transcription 3 (Stat3)
      was activated by overexpressing Stat3C in a newly established c-fms
      rtTA/(TetO)(7)-CMV-Stat3C bitransgenic mouse model. In this system, Stat3C-Flag
      fusion protein was overexpressed in myeloid lineage cells after doxycycline
      treatment. Stat3C overexpression induced systematic elevation of macrophages and
      neutrophils in multiple organs. In the lung, tissue neoplastic pneumocyte
      proliferation was observed. After in vitro cultured hSP-B 1.5-kb lacZ BMSCs were
      injected into the bitransgenic mice, BMSCs were able to repopulate in multiple
      organs, self-renew in the bone marrow and spleen, and convert into alveolar type
      II epithelial cells. The bone marrow transplantation study indicated that
      increases of myeloid lineage cells and BMSC-AT II cell conversion were due to
      malfunction of myeloid progenitor cells as a result of Stat3C overexpression. The
      study supports the concept that activation of the Stat3 pathway in myeloid cells
      plays an important role in BMSC function, including homing, repopulating and
      converting into residential AT II epithelial cells in the lung.

PMID- 22864833
TI  - Complete mitochondrial genome of the Japanese snapping shrimp Alpheus japonicus
      (Crustacea: Decapoda: Caridea): gene rearrangement and phylogeny within Caridea.
AB  - The complete sequence of the mitochondrial genome of the Japanese snapping shrimp
      Alpheus japonicus Miers (Crustacea: Decapoda: Caridea) is presented here. A
      comparative analysis based on the currently available mitochondrial genomic data
      revealed many previously unknown characteristics of the mitochondrial genomes of
      caridean shrimps. The A. japonicus mitochondrial genome is 16487 bp long and
      contains the typical set of 37 metazoan genes. The gene arrangements in the
      mitochondrial genomes of four previously studied carideans (Macrobrachium
      rosenbergii, M. nipponense, M. lanchesteri and Halocaridina rubra) were found to
      be identical to the pancrustacean ground pattern; thus, it was considered that
      gene rearrangements probably did not occur in the suborder Caridea. In the
      present study, a translocation of the trnE gene involving inversion was found in
      Alpheus mitochondrial genomes. This phenomenon has not been reported in any other
      crustacean mitochondrial genome that has been studied so far; however, the
      translocation of one transfer RNA gene (trnP or trnT) was reported in the
      mitochondrial genome of Exopalaemon carinicauda. When the ratios of the
      nonsynonymous and synonymous substitutions rates (Ka/Ks) for the 13 protein
      coding genes from two Alpheus species (A. japonicus and A. distinguendus) and
      three Macrobrachium species (M. rosenbergii, M. nipponense, M. lanchesteri) were
      calculated, the Ka/Ks values for all the protein coding genes in Alpheus and
      Macrobrachium mitochondrial genomes were found to be less than 1 (between 0.0048
      and 0.2057), indicating that a strong purification selection had occurred. The
      phylogenetic tree that was constructed based on the mitochondrial protein coding
      genes in the genomes of nine related species indicated that Palaemonidae and
      Alpheidae formed a monophyly and shared a statistically significant relationship,
      (Palaemonidae+Alpheidae)+Atyidae, at the family level.

PMID- 22864834
TI  - Increased susceptibility of algal symbionts to photo-inhibition resulting from
      the perturbation of coral gastrodermal membrane trafficking.
AB  - The stability of cnidarian-dinoflagellate endosymbioses is dependent upon
      communication between the host gastrodermal cell and the symbionts housed within
      it. Although the molecular mechanisms remain to be elucidated, existing evidence
      suggests that the establishment of these endosymbioses may involve the sorting of
      membrane proteins. The present study examined the role of host gastrodermal
      membranes in regulating symbiont (genus Symbiodinium) photosynthesis in the stony
      coral Euphyllia glabrescens. In comparison with the photosynthetic behavior of
      Symbiodinium in culture, the Symbiodinium populations within isolated symbiotic
      gastrodermal cells (SGCs) exhibited a significant degree of photo-inhibition, as
      determined by a decrease in the photochemical efficiency of photosystem II (F
      (v)/F (m)). This photo-inhibition coincided with increases in plasma membrane
      perturbation and oxidative activity in the SGCs. Membrane trafficking in SGCs was
      examined using the metabolism of a fluorescent lipid analog, N-[5-(5,7-dimethyl
      boron dipyrromethene difluoride)-1-pentanoyl]-D-erythro-Sphingosylphosphoryl
      choline (BODIPY-Sphingomyelin or BODIPY-SM). Light irradiation altered both
      membrane distribution and trafficking of BODIPY-SM, resulting in metabolic
      changes. Cholesterol depletion of the SGC plasma membranes by methyl-beta
      cyclodextrin retarded BODIPY-SM degradation and further augmented Symbiodinium
      photo-inhibition. These results indicate that Symbiodinium photo-inhibition may
      be related to perturbation of the host gastrodermal membrane, providing evidence
      for the pivotal role of host membrane trafficking in the regulation of this
      environmentally important coral-dinoflagellate endosymbiosis.

PMID- 22864835
TI  - Qualitative and quantitative analyses of influenza virus receptors in trachea and
      lung tissues of humans, mice, chickens and ducks.
AB  - To accurately determine the expression and distribution patterns of two influenza
      virus receptors (SAalpha2,3-gal and SAalpha2,6-gal) in trachea and lung tissues
      of humans, mice, chickens and ducks, we analyzed lectin immunofluorescence
      stainings of various tissue sections qualitatively and quantitatively. Results
      from the qualitative analysis showed that both influenza virus receptors were
      expressed in lung tissues of humans, mice, chickens and ducks as well as trachea
      tissues of mice and ducks. However, SAalpha2,6-gal receptor was expressed only in
      the human trachea tissue and SAalpha2,3-gal receptor was expressed only in the
      chicken trachea tissue. Results from the quantitative analysis demonstrated that
      both receptors were expressed in trachea tissues of human and mouse, as well as
      in lung tissues of humans, chickens and ducks. Meanwhile, our results also showed
      that the expression and distribution of influenza virus receptors in the same
      tissue were not always uniform, indicating that their distribution and expression
      in various tissues are not simply the distinction between the presence or absence
      of receptors, but rather the difference in the amount of expressed receptors.

PMID- 22864836
TI  - A genome-wide association study of Alzheimer's disease using random forests and
      enrichment analysis.
AB  - Alzheimer's disease (AD) is a serious neurodegenerative disorder and its cause
      remains largely elusive. In past years, genome-wide association (GWA) studies
      have provided an effective means for AD research. However, the univariate method
      that is commonly used in GWA studies cannot effectively detect the biological
      mechanisms associated with this disease. In this study, we propose a new strategy
      for the GWA analysis of AD that combines random forests with enrichment analysis.
      First, backward feature selection using random forests was performed on a GWA
      dataset of AD patients carrying the apolipoprotein gene (APOEE4) and 1058
      susceptible single nucleotide polymorphisms (SNPs) were detected, including
      several known AD-associated SNPs. Next, the susceptible SNPs were investigated by
      enrichment analysis and significantly-associated gene functional annotations,
      such as 'alternative splicing', 'glycoprotein', and 'neuron development', were
      successfully discovered, indicating that these biological mechanisms play
      important roles in the development of AD in APOEE4 carriers. These findings may
      provide insights into the pathogenesis of AD and helpful guidance for further
      studies. Furthermore, this strategy can easily be modified and applied to GWA
      studies of other complex diseases.

PMID- 22864837
TI  - Spatiotemporal patterns of the fish assemblages downstream of the Gezhouba Dam on
      the Yangtze River.
AB  - An explicit demonstration of the changes in fish assemblages is required to
      reveal the influence of damming on fish species. However, information from which
      to draw general conclusions regarding changes in fish assemblages is insufficient
      because of the limitations of available approaches. We used a combination of
      acoustic surveys, gillnet sampling, and geostatistical simulations to document
      the spatiotemporal variations in the fish assemblages downstream of the Gezhouba
      Dam, before and after the third impoundment of Three Gorges Reservoir (TGR). To
      conduct a hydroacoustic identification of individual species, we matched the size
      distributions of the fishes captured by gillnet with those of the acoustic
      surveys. An optimum threshold of target strength of -50 dB re 1 m(2) was defined,
      and acoustic surveys were purposefully extended to the selected fish assemblages
      (i.e., endemic Coreius species) that was acquired by the size and species
      selectivity of the gillnet sampling. The relative proportion of fish species in
      acoustic surveys was allocated based on the composition (%) of the harvest in the
      gillnet surveys. Geostatistical simulations were likewise used to generate
      spatial patterns of fish distribution, and to determine the absolute abundance of
      the selected fish assemblages. We observed both the species composition and the
      spatial distribution of the selected fish assemblages changed significantly after
      implementation of new flow regulation in the TGR, wherein an immediate sharp
      population decline in the Coreius occurred. Our results strongly suggested that
      the new flow regulation in the TGR impoundment adversely affected downstream fish
      species, particularly the endemic Coreius species. To determine the factors
      responsible for the decline, we associated the variation in the fish assemblage
      patterns with changes in the environment and determined that substrate erosion
      resulting from trapping practices in the TGR likely played a key role.

PMID- 22864838
TI  - Comparative study on the performance of textural image features for active
      contour segmentation.
AB  - We present a computerized method for the semi-automatic detection of contours in
      ultrasound images. The novelty of our study is the introduction of a fast and
      efficient image function relating to parametric active contour models. This new
      function is a combination of the gray-level information and first-order
      statistical features, called standard deviation parameters. In a comprehensive
      study, the developed algorithm and the efficiency of segmentation were first
      tested for synthetic images. Tests were also performed on breast and liver
      ultrasound images. The proposed method was compared with the watershed approach
      to show its efficiency. The performance of the segmentation was estimated using
      the area error rate. Using the standard deviation textural feature and a 5*5
      kernel, our curve evolution was able to produce results close to the minimal area
      error rate (namely 8.88% for breast images and 10.82% for liver images). The
      image resolution was evaluated using the contrast-to-gradient method. The
      experiments showed promising segmentation results.

PMID- 22864839
TI  - Latest notable achievements in genomics.

PMID- 22864840
TI  - Recent progress in microRNA study: benefits from technique advance.

PMID- 22864841
TI  - Microfluidic technology for molecular diagnostics.
AB  - Molecular diagnostics have helped to improve the lives of millions of patients
      worldwide by allowing clinicians to diagnose patients earlier as well as
      providing better ongoing therapies. Point-of-care (POC) testing can bring these
      laboratory-based techniques to the patient in a home setting or to remote
      settings in the developing world. However, despite substantial progress in the
      field, there still remain many challenges. Progress in molecular diagnostics has
      benefitted greatly from microfluidic technology. This chapter aims to summarise
      the more recent advances in microfluidic-based molecular diagnostics. Sections
      include an introduction to microfluidic technology, the challenges of molecular
      diagnostics, how microfluidic advances are working to solve these issues, some
      alternative design approaches, and detection within these systems. 

PMID- 22864842
TI  - [Do physicians know and use mandatory quality reports?].
AB  - OBJECTIVE: Physicians should be principal recipients of quality reports because
      they play a major role in referral decisions. The purpose of this study was to
      determine physicians' awareness and use of Germany's mandatory hospital quality
      reports. METHOD: A retrospective observational study was carried out through
      structured telephone interviews of a stratified random sample of 300 physicians
      working in ambulatory care in Germany. We analysed absolute and relative
      frequencies of physicians' awareness and use of quality reports. Additionally we
      analysed physicians' awareness and use of quality reports in relation to age,
      sex, specialty, practice type and region of practice using binary regression
      analysis. RESULTS: Less than half of the physicians were aware of the quality
      reports. Younger physicians were significantly more aware of the reports but did
      not use them more often than their older colleagues. Overall 10 % of the
      physicians already used them for counselling patients. Taking physicians' use of
      online comparative hospital guides into account, the combined total use was 14 %.
      CONCLUSIONS: Germany's mandatory hospital quality reports play only a minor role
      in physicians counselling of patients who need hospital care because too few
      physicians know and use the reports.

PMID- 22864843
TI  - [Long-term prescription of benzodiazepines and non-benzodiazepines].
AB  - BACKGROUND: The number of persons with a dependence on prescription drugs such as
      sedatives or tranquilizers in Germany is estimated at between 1.4 and 1.9
      million. According to national addiction treatment documentations only very few
      of them seek help in specialised treatment services. The majority of prescription
      drug-dependent people use benzodiazepines. This medication is usually prescribed
      by physicians and according to German guidelines it should be prescribed only for
      limited, short periods and in low doses. OBJECTIVE: This study aims to determine
      the extent of the problematic prescription of benzodiazepines and non
      benzodiazepines. METHODS: We used prescription data from the Northern Germany
      Computing Centre for Pharmacies registered between 2005 and 2007. For the German
      regions of Hamburg, Bremen and Schleswig-Holstein, benzodiazepine prescriptions
      during an individual prospective period of 12 months were analysed. RESULTS: From
      July 2005 to June 2006, 294 143 prescriptions of benzodiazepines and non
      benzodiazepines were recorded for 78 456 citizens of Hamburg and billed at the
      expenses of the governmental health insurance funds. In the course of one
      observed patient year, 51.1% of benzodiazepine prescriptions were in accordance
      with the German guidelines. 15.6% of the patients were supplied on a long-term
      basis (0.5-1 DDD during at least 2 months). Prescriptions for women and persons
      older than 70 years were disproportionately high. Compared with the Federal
      states of Bremen and Schleswig-Holstein, Hamburg does not show an exceptional
      position. CONCLUSION: The prescription of benzodiazepines which is not in
      accordance with the relevant national guidelines is widespread and calls for
      discussion and education among physicians and pharmacists. Furthermore,
      professional addiction services should reconsider ways to help and attract
      prescription drug-dependent people to cover their needs, as their numbers will
      grow in an aging society.

PMID- 22864844
TI  - [Effects of inpatient rehabilitation on long-term health-related quality of life
      in patients with cancer and rheumatoid arthritis: an analysis based on the
      classification of therapeutic procedures codes (KTL)].
AB  - OBJECTIVES: This explorative study investigated associations among the amount of
      different rehabilitative interventions, based on the classification of
      therapeutic procedures codes (KTL), and long-term health-related quality of life
      in patients with cancer or rheumatoid arthritis. METHODS: 3 therapeutic modules
      of rehabilitative interventions were defined on the basis of KTL codes: (i)
      somatic interventions, (ii) psychological interventions, and (iii) medical
      counselling. Based on a median-split, patients were classified in 2 groups with
      low vs. high amount of rehabilitative interventions. Health-related quality of
      life was assessed on admission, at discharge from rehabilitative stay, as well as
      3 and 12 months after discharge using the SF-12 health survey. RESULTS: 166
      patients with chronic arthritis and 159 patients with cancer undergoing inpatient
      rehabilitation were included in the analysis. Arthritis patients who received a
      high amount of somatic interventions showed a significant improvement in the SF
      12 mental health component summary score up to 12 months after discharge
      (p<0.05). Cancer patients who received a high amount of psychological
      interventions showed higher SF-12 physical health component summary scores at 3
      and 12 months follow-up (p<0.05). CONCLUSION: The results suggest differential
      relationships between amount of rehabilitative interventions and long-term
      rehabilitation outcome in 2 different disease groups. Routine classification of
      rehabilitative procedures (KTL) codes can be used for analysing dose-response
      relationships, although open questions remain concerning the validity of KTL
      codes.

PMID- 22864846
TI  - [Cost analysis of telemedical treatment of stroke].
AB  - BACKGROUND: Telemedicine-enabled stroke networks increase the probability of a
      good clinical outcome. There is a shortage of evidence about the effects of this
      new approach on costs for inpatient care and nursing care. METHODS: We analysed
      health insurance and nursing care fund data of a statutory health insurance
      company (AOK Bayern). Data from stroke patients initially treated in a TeleStroke
      network (TEMPiS - telemedical project for integrative stroke care) between
      community hospitals and academic stroke centres were compared to data of matched
      hospitals without specialised stroke care and telemedical support. Costs for
      nursing care were obtained over a 30-month period after the initial stroke. To
      rule out pre-existing differences between network and control hospitals, costs of
      stroke care were also analysed during a time period before network
      implementation. FINDINGS: 1 277 patients (767 in intervention, 510 in control
      hospitals) were analysed in the post-implementation period. An increased
      proportion of patients treated in intervention hospitals had a favourable outcome
      concerning the level of required nursing care. Patients in intervention hospitals
      had higher costs for acute inpatient care (5 309 ? vs. 4 901 ?, p=0.04), but
      lower nursing care fund costs (3 946 ? vs. 5 132 ?; p=0.04). There was no
      difference in relation to absolute total costs obtained in the post
      implementation period. However, nursing care costs per survived year were
      significantly lower in intervention hospitals (1 953 ? vs. 2 635 ?; p=0.005). No
      significant differences were found in the pre-implementation period. CONCLUSIONS:
      Considering both health insurance and nursing care fund costs, the incremental
      costs for TeleStroke network care in hospitals are compensated by savings in
      outpatient care.

PMID- 22864845
TI  - [Health locus of control of patients in disease management programmes].
AB  - Health locus of control beliefs plays a major role in improving self-management
      skills of the chronically ill - a main goal in disease management programmes
      (DMP). This study aims at characterising participants in disease management
      regarding their health locus of control. Data are based on 4 cross-sectional
      postal surveys between spring and autumn of 2006 and 2007 within the Health Care
      Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are
      chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A
      high internal locus of control (HLC) occurs significantly less often in DMP
      patients than in normal chronically ill patients (and healthy people) controlling
      for age, gender and social class. With increasing age, a high internal locus of
      control is also significantly less likely. When comparing healthy people, the
      chronically ill and the DMP participants a social gradient of a high internal
      locus of control belief can be observed. The weaker internal and higher doctor
      related external locus of control of DMP participants should be carefully
      observed by the physician when trying to strengthen the patients' self-management
      skills. Evaluators of DMP should take into account the different baselines of DMP
      patients and relevant control groups and incorporate these differences into the
      evaluation. 

PMID- 22864847
TI  - [Efficacy and efficiency of searches for a physician using physician search and
      evaluation portals in comparison with Google].
AB  - OBJECTIVES: The Internet provides ways for patients to obtain information about
      doctors. The study poses the question whether it is possible and how long it
      takes to find a suitable doctor with an Internet search. It focuses on the
      effectiveness and efficiency of the search. Specialised physician rating and
      searching portals and Google are analysed when used to solve specific tasks.
      METHODS: The behaviour of volunteers when searching a suitable ophthalmologist,
      dermatologist or dentist was observed in a usability lab. Additionally,
      interviews were carried out by means of structured questionnaires to measure the
      satisfaction of the users with the search and their results. Three physician
      rating and searching portals that are frequently used in Germany (Jameda.de,
      DocInsider.de and Arztauskunft.de) were analysed as well as Google. RESULTS: When
      using Arztauskunft and Google most users found an appropriate physician. When
      using Docinsider or Jameda they found fewer doctors. Additionally, the time
      needed to locate a suitable doctor when using Docinsider and Jameda was higher
      compared to the time needed when using the Arztauskunft and Google. The
      satisfaction of users who used Google was significantly higher in comparison to
      those who used the specialised physician rating and searching portals.
      CONCLUSION: It emerged from this study that there is no added value when using
      specialised physician rating and searching portals compared to using the search
      engine Google when trying to find a doctor having a particular specialty. The
      usage of several searching portals is recommended to identify as many suitable
      doctors as possible.

PMID- 22864848
TI  - [Tobacco smoking and alcohol consumption among apprentices at vocational schools
      in West Pomerania, Germany].
AB  - Little is known about tobacco smoking and health risk drinking among apprentices
      at vocational schools. The aim of this study was to determine the proportions of
      subjects who smoke or drink alcohol in a risky way, their preparedness to stop
      smoking, and the proportions of smokers and risk drinkers according to
      occupational groups and general school education. The methods included a survey
      of all apprentices in their first year of vocational training and all trainees in
      a course of preparation for occupation in a north-eastern region of Germany. All
      vocational schools of the study region participated. At the time of the survey,
      77.9% of the apprentices were present. Among them, 99.8% (N=1 124) filled in
      questionnaires. The data revealed that among the total sample 61.2% were daily or
      less than daily current smokers. Among adults, 8.2%, among those at age 17 or
      younger 12.9% had a mean daily consumption of more than 12 grams (females) or
      more than 24 grams (males) of pure alcohol. These proportions were 12.6-18.0%
      among apprentices of blue collar occupations and 2.8-6.5% among apprentices of
      white collar or health occupations. Among subjects who had left school without
      graduation, 85.0%, and among those with the highest school education 36.9% were
      current smokers. It is concluded that vocational schools are a suitable and
      essential setting to reach a high risk population concerning tobacco smoking or
      unhealthy alcohol consumption.

PMID- 22864850
TI  - Development of glycoscience in China.

PMID- 22864849
TI  - Protection by chrysin, apigenin, and luteolin against oxidative stress is
      mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate
      cysteine ligase in rat primary hepatocytes.
AB  - Chrysin, apigenin, and luteolin are flavones that differ in their number of
      hydroxyl groups in the B ring. In this study, we investigated the protection by
      chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced
      oxidative stress and the possible mechanisms involved in rat primary hepatocytes.
      Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein
      expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL)
      catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular
      glutathione (GSH) content and the ratio of GSH to oxidized GSH. Among the
      flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM
      protein expression and GSH content. Cellular reactive oxygen species production
      induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and
      luteolin (P < .05), and this protection was reversed by the GCL inhibitor l
      buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin. Chrysin,
      apigenin, and luteolin activated extracellular signal-regulated protein kinase 2
      (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation,
      nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE
      dependent luciferase activity. Both ERK2 and Nrf2 siRNAs attenuated chrysin
      induced HO-1, GCLC, and GCLM protein expression. Taken together, these results
      suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative
      stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the
      ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.

PMID- 22864851
TI  - The influence of in situ chemical oxidation on microbial community composition in
      groundwater contaminated with chlorinated solvents.
AB  - In situ chemical oxidation with permanganate has become an accepted remedial
      treatment for groundwater contaminated with chlorinated solvents. This study
      focuses on the immediate and short-term effects of sodium permanganate (NaMnO(4))
      on the indigenous subsurface microbial community composition in groundwater
      impacted by trichloroethylene (TCE). Planktonic and biofilm microbial communities
      were studied using groundwater grab samples and reticulated vitreous carbon
      passive samplers, respectively. Microbial community composition was analyzed by
      terminal restriction fragment length polymorphism and a high-density phylogenetic
      microarray (PhyloChip). Significant reductions in microbial diversity and biomass
      were shown during NaMnO(4) exposure, followed by recovery within several weeks
      after the oxidant concentrations decreased to <1 mg/L. Bray-Curtis similarities
      and nonmetric multidimensional scaling showed that microbial community
      composition before and after NaMnO(4) was similar, when taking into account the
      natural variation of the microbial communities. Also, 16S rRNA genes of two
      reductive dechlorinators (Desulfuromonas spp. and Sulfurospirillum spp.) and
      diverse taxa capable of cometabolic TCE oxidation were detected in similar
      quantities by PhyloChip across all monitoring wells, irrespective of NaMnO(4)
      exposure and TCE concentrations. However, minimal biodegradation of TCE was
      observed in this study, based on oxidized conditions, concentration patterns of
      chlorinated and nonchlorinated hydrocarbons, geochemistry, and spatiotemporal
      distribution of TCE-degrading bacteria.

PMID- 22864852
TI  - Priming effects of the endophytic fungus Phomopsis liquidambari on soil mineral N
      transformations.
AB  - Nitrogen (N) is a crucial nutrient for soil biota, and its cycling is determined
      by the organic carbon decomposing process. Some endophytic fungi are latent
      saprotrophs that trigger their saprotrophic metabolism to promote litter organic
      matter cycling as soon as the host tissue senesces or dies. However, the effects
      of endophytic fungi on litter and soil N dynamics in vitro have rarely been
      investigated. In this study, we investigated N dynamics (total and mineral N) in
      both litter and soil in incubations of a pure culture of an endophytic fungus
      Phomopsis liquidambari with litter and following soil burial of the litter. Soil
      enzymes and microbial communities participating in the N transformations were
      also investigated. A pure culture of P. liquidambari released litter NH (4) (+) 
      N in the initial stages (10 days) of the incubation. However, following soil
      burial, the presence of both P. liquidambari and soil ammonia-oxidizing bacteria
      (AOB) resulted in an increase in soil NO (3) (-) -N. These results indicate that
      the endophytic fungus P. liquidambari in vitro stimulates organic mineralization
      and promote NH (4) (+) -N release. Such effects triggered soil AOB-driven
      nitrification process.

PMID- 22864853
TI  - Microbial community compositional shifts in bleached colonies of the Brazilian
      reef-building coral Siderastrea stellata.
AB  - The association of metazoan, protist, and microbial communities with
      Scleractinian corals forms the basis of the coral holobiont. Coral bleaching
      events have been occurring around the world, introducing changes in the delicate
      balance of the holobiont symbiotic interactions. In this study, Archaea,
      bacteria, and eukaryotic phototrophic plastids of bleached colonies of the
      Brazilian coral Siderastrea stellata were analyzed for the first time, using 16S
      rRNA gene libraries. Prokaryotic communities were slightly more diverse in
      healthy than in bleached corals. However, the eukaryotic phototrophic plastids
      community was more diverse in bleached corals. Archaea phylogenetic analyses
      revealed a high percentage of Crenarchaeota sequences, mainly related to
      Nitrosopumilus maritimus and Cenarchaeum symbiosum. Dramatic changes in bacterial
      community composition were observed in this bleaching episode. The dominant
      bacterial group was Alphaproteobacteria followed by Gammaproteobacteria in
      bleached and Betaproteobacteria in healthy samples. Plastid operational taxonomic
      units (OTUs) from both coral samples were mainly related to red algae
      chloroplasts (Florideophycea), but we also observed some OTUs related to green
      algae chloroplasts (Chlorophyta). There seems to be a strong relationship between
      the Bacillariophyta phylum and our bleached coral samples as clones related to
      members of the diatom genera Amphora and Nitzschia were detected. The present
      study reveals information from a poorly investigated coral species and improves
      the knowledge of coral microbial community shifts that could occur during
      bleaching episodes.

PMID- 22864854
TI  - Bacterial consortium of Millepora dichotoma exhibiting unusual multifocal lesion
      event in the Gulf of Eilat, Red Sea.
AB  - Colonies of the hydrocoral Millepora dichotoma along the Gulf of Eilat are
      exhibiting unusual tissue lesions in the form of white spots. The emergence and
      rapid establishment of these multifocal tissue lesions was the first of its kind
      reported in this region. A characterization of this morphological anomaly
      revealed bleached tissues with a significant presence of bacteria in the tissue
      lesion area. To ascertain possible differences in microbial biota between the
      lesion area and non-affected tissues, we characterized the bacterial diversity in
      the two areas of these hydrocorals. Both culture-independent (molecular) and
      culture-dependent assays showed a shift in bacterial community structure between
      the healthy and affected tissues. Several 16S rRNA gene sequences retrieved from
      the affected tissues matched sequences of bacterial clones belonging to
      Alphaproteobacteria and Bacteroidetes members previously associated with various
      diseases in scleractinian corals.

PMID- 22864855
TI  - Right ventricular pulmonary hypertension.
AB  - In heart failure (HF) syndrome, the development of pulmonary hypertension (PH),
      right ventricular (RV) dysfunction and failure are ominous prognostic signs.
      Pathophysiology, clinical interest and targeted therapeutic approaches for left
      sided PH and its consequences on RV function have been traditionally confined to
      advanced HF stages. Community- and population-based studies have clearly
      indicated that PH is frequent even in HF patients with preserved ejection
      fraction, and may carry important prognostic implications in normal ageing as
      well. HF guidelines are inconclusive on both preventive and curative strategies
      for left-sided PH and its consequences on RV function. The search for new
      therapeutic opportunities targeted on pulmonary vascular and right heart
      remodeling are an important challenge for the future.

PMID- 22864856
TI  - Gender differences in the pathophysiology, clinical presentation, and outcomes of
      ischemic heart failure.
AB  - Despite advances in the treatment of acute myocardial infarction (MI), heart
      failure (HF) remains a frequent acute and long-term outcome of ischemic heart
      disease (IHD). In response to acute coronary ischemia, women are relatively
      protected from apoptosis, and experience less adverse cardiac remodeling than
      men, frequently resulting in preservation of left ventricular size and ejection
      fraction. Despite these advantages, women are at increased risk for HF-
      complicating acute MI when compared with men. However, women with HF retain a
      survival advantage over men with HF, including a decreased risk of sudden death.
      Sex-specific treatment of HF has been hindered by historical under-representation
      of women in clinical trials, though recent work has suggested that women may have
      a differential response to some therapies such as cardiac resynchronization. This
      review highlights the sex differences in the pathophysiology, clinical
      presentation and outcomes of ischemic heart failure and discusses key areas
      worthy of further investigation.

PMID- 22864859
TI  - Enhanced emission of ultra-small-sized LaF3:RE3+ (RE = Eu, Tb) nanoparticles
      through 1,2,4,5-benzenetetracarboxylic acid sensitization.
AB  - Uniform, ultra-small-sized and well-water-dispersible LaF(3) nanoparticles doped
      with trivalent rare earth (RE) ions (Eu(3+) or Tb(3+)) have been synthesized by a
      simple, low temperature synthesis route. The nanoparticles, with sizes of about
      3.2 nm (for those doped with Eu(3+)) and 3.0 nm (for those doped with Tb(3+)),
      are roughly spherical and monodisperse. 1,2,4,5-Benzenetetracarboxylic acid
      (labeled as BA) as sensitizer has been bonded to the surface of the
      nanoparticles, which can sensitize the emission of RE(3+) in the LaF(3)
      nanoparticles. The BA-LaF(3):RE(3+) (RE = Eu or Tb) nanoparticles have a broad
      absorption band in the UV domain, and show enhanced luminescence of RE(3+) based
      on an energy transfer from BA ligands to RE(3+) ions (i.e. the so-called "antenna
      effect"). Due to the dual protection of organic ligands (BA) and inorganic
      matrices (LaF(3)), BA-LaF(3):RE(3+) (RE = Eu or Tb) nanoparticles have longer
      excited state lifetimes than LaF(3):RE(3+) (RE = Eu or Tb) nanoparticles as well
      as lanthanide coordination polymers of BA.

PMID- 22864858
TI  - Mild prolonged hypothermia for large intracerebral hemorrhage.
AB  - BACKGROUND: Perihemorrhagic edema (PHE) develops after intracerebral hemorrhage
      (ICH). It can worsen the clinical situation by its additional mass effect.
      Therapeutic hypothermia (TH) might be an effective method to control PHE, but has
      not been sufficiently studied in ICH patients. METHODS: We report data on n = 25
      consecutive patients with large supratentorial ICH (volume > 25 ml) who were
      treated by mild TH of 35  degrees C for 8-10 days. Body temperature was
      controlled by endovascular cooling catheters. We followed the clinical course
      during hospital stay and measured volumes of ICH and PHE in regularly performed
      serial cranial computed tomography. Outcome was assessed after 3 and 12 months.
      These data were compared to a historical group of n = 25 patients with large ICH.
      RESULTS: While PHE continuously increased in the historical control group up to
      day 10, PHE volumes in the hypothermia group remained stable. There was a
      significant difference from day 3 after symptom onset. Shivering (36 %) and
      pneumonia (96 %) were the most frequent complications during TH. Mortality rate
      was 8.3 % in TH versus 16.7 % in the control group after 3 months and 28 versus
      44 % after 1 year. CONCLUSIONS: These data support the promising results of our
      first case series on TH in large ICH. TH prevents the development of PHE and its
      complications. Side effects of TH appeared often, but could be treated
      sufficiently. Therefore, TH might represent a new therapy for PHE after large
      ICH, but has to be further tested in randomized trials.

PMID- 22864857
TI  - Atrial fibrillation in heart failure.
AB  - Atrial fibrillation and heart failure are both associated with increased
      morbidity as well as mortality, and there is a complex interaction between the
      two conditions. The increasing prevalence and incidence rates of AF and CHF, as
      well as emerging novel but relatively expensive treatments and interventions,
      have compounded the significant public health impact at a global level. Ongoing
      investigative efforts continue to advance the knowledge of the complex interplay
      between these two conditions. This review critically assesses the current
      evidence in the field regarding prognostication metrics, drug therapy, and
      interventions for AF in CHF. We will summarize the important new findings
      published over the last year, with a focus on the latest advances that are of
      clinical relevance.

PMID- 22864860
TI  - Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as
      biomarkers in diabetic retinopathy.
AB  - The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several
      transcriptional factors and signaling pathways and a potent modulator of genes
      involved in inflammation, angiogenesis and fibrosis. This study was conducted to
      measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and
      acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative
      diabetic retinopathy (PDR) and to correlate their levels with clinical disease
      activity and the level of vascular endothelial growth factor (VEGF). In addition,
      we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the
      retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic
      patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and
      retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels
      in vitreous samples from PDR patients were significantly higher than those in
      control patients without diabetes (p < 0.001 for all comparisons). ATX levels in
      PDR with active neovascularization and inactive PDR were significantly lower than
      those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with
      active neovascularization were significantly higher than those in inactive PDR
      and nondiabetic patients (p < 0.001 for both comparisons). A significant
      correlation was observed between levels of VEGF and levels of AGK in PDR patients
      (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in
      the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic
      rats compared to nondiabetic controls, whereas ATX was significantly
      downregulated. Our findings suggest that ATX-AGK-LPA signaling axis might be an
      important player in the development and progression of diabetic retinopathy.

PMID- 22864861
TI  - Comparative evaluation of five Beauveria isolates for housefly (Musca domestica
      L.) control and growth optimization of selected strain.
AB  - Pathogenic potential of five native Beauveria isolates was assessed against
      housefly adult and larvae in laboratory bioassays. Beauveria isolate Beauveria
      bassiana HQ917687 showed highest virulence with 72.3 and 100 % mortality of
      larvae and adults of Musca domestica, respectively. Other Beauveria isolates
      caused 36-52 % housefly larval mortality while the adult mortalities varied
      between 72 and 82 %. B. bassiana HQ917687 also showed the fastest killing
      activity with LT(50) of 4 days (for larvae) and 3 days (for adults). This isolate
      showing highest virulence was selected for its growth optimization in terms of
      biomass and spore production using response surface methodology. The optimum
      value of temperature, yeast extract, and pH for maximum biomass and spore
      production was predicted as 27  degrees C, 5.00 g/l, and 6.75, respectively.
      Temperature was found to be the most critical factor influencing biomass and
      spore yield of the fungus and even nullified the effects of other factors at
      sufficiently higher value. The results obtained in this study depict the
      significance of appropriate strain selection and process parameter optimization
      in order to facilitate mass production of biocontrol agents.

PMID- 22864862
TI  - Intermediate snail hosts of French Fasciola hepatica: Lymnaea neotropica and
      Lymnaea viatrix are better hosts than local Galba truncatula.
AB  - Allopatric and sympatric infections of Lymnaea neotropica and Lymnaea viatrix
      var. ventricosa with Argentinean and French isolates of Fasciola hepatica were
      carried out to determine the capacity of these snails to produce metacercariae
      and to verify if this capacity changed with snail generation. The same process
      was also made with a French population of Galba truncatula known to be highly
      susceptible to French isolates of the parasite. In each lymnaeid species
      separately considered, the survival rate at day 30 post-exposure and prevalence
      of F. hepatica infection in the group infected with Argentinean miracidia were
      significantly greater than those recorded in the corresponding French one.
      Compared to infected G. truncatula, both South American lymnaeids had longer
      patent periods and produced a higher number of metacercariae. The highest
      infections were noted with L. v. ventricosa. In the three snail species,
      metacercarial production was more important with the Argentinean isolate of
      miracidia than with the French one. If three successive generations of L. v.
      ventricosa are exposed to the same French isolate of miracidia, cercarial
      production significantly increased from parents to the F2 generation, while the
      other characteristics of infection only showed insignificant variations. L.
      neotropica and L. v. ventricosa are better intermediate hosts for French F.
      hepatica than local G. truncatula. The numerical increase of shed cercariae in
      the F1 and F2 generations of L. v. ventricosa demonstrates a rapid adaptation of
      this species to the French isolate of the parasite.

PMID- 22864863
TI  - Fungal-mediated nano silver: an effective adulticide against mosquito.
AB  - Fungi as such are known to be an effective mosquito control agent. In the present
      investigation, the effect of silver nanoparticles synthesized with Chrysosporium
      keratinophilum, Verticillium lecanii, and Fusarium oxysporum f.sp. pisi has been
      evaluated against the adult mosquito of filariasis vector Culex quinquefasciatus.
      The silver nanoparticles were characterized by using the UV-Vis spectrophotometer
      and X-ray diffraction techniques. The micrographs of silver nanoparticles were
      obtained by transmission electron microscope and scanning electron microscope.
      Elemental analysis on single particle was carried out by EDX analysis. The
      characterization study confirmed different shapes and sizes of silver
      nanoparticles. The efficacy test was performed at five different concentrations
      for a period of 24 h by the probit analysis. The C. quinquefasciatus has shown
      higher efficacy against the silver nanoparticles synthesized with C.
      keratinophilum and V. lecanii (lethal concentration (LC)(50) 0.19 and 0.4
      MUl/cm(2); LC(90) 2.4 and 3.2 MUl/cm(2); and LC(99) 4.0 and 5.6 MUl/cm(2)) after
      22 h of exposure. While the silver nanoparticles synthesized with F. oxysporum
      f.sp. pisi were found to be less effective against the C. quinquefasciatus, the
      silver nanoparticles synthesized by C. keratinophilum and V. lecanii were found
      to be more effective than those generated with the help of F. oxysporum f.sp.
      pisi and C. quinquefasciatus. The use of fungus-mediated silver nanoparticles is
      a rapid, environmentally safer, and greener approach for vector control strategy
      and is adaptable globally.

PMID- 22864864
TI  - Treatment of third-stage larvae of Toxocara cati with milbemycin oxime plus
      praziquantel tablets and emodepside plus praziquantel spot-on formulation in
      experimentally infected cats.
AB  - Toxocara cati is the most prevalent gastrointestinal helminth in cats worldwide,
      with cats of all ages at risk of infection. An anthelminthic treatment that not
      only affects the gut-dwelling stages of this parasite but is also effective
      against developmental stages in the tissue has the advantage that the pathology
      caused by migrating larvae is minimized and the need for repeated treatments is
      reduced. This study was conducted to evaluate the efficacy of milbemycin
      oxime/praziquantel tablets (Milbemax(r), Novartis) against third-stage larvae of
      T. cati in comparison to a spot-on formulation of emodepside and praziquantel
      (Profender(r), Bayer). Twenty-four kittens were experimentally infected with T.
      cati and randomly allocated to three study groups. Treatments were performed at
      the minimum therapeutic dosage 5 days after the experimental infection. The
      development of patent infections was monitored and all cats were dewormed 50 days
      post-infection. Efficacies were calculated based on counts of excreted worms in
      the treated groups compared to a negative control group. Seven of the eight cats
      in the negative control group developed a patent T. cati infection and all cats
      were excreting worms at the end of the study (geometric mean worm count 18.1). No
      efficacy could be observed for the milbemycin oxime-treated animals. All cats
      developed a patent infection and excreted worms (geometric mean worm count 27.7).
      The treatment with Profender(r) was 98.5 % effective against L3 of T. cati. One
      cat developed a patent infection and was excreting worms at the end of the study
      (geometric mean worm count 0.3). No adverse reactions were noted in either
      treatment group.

PMID- 22864865
TI  - Impact of acute pulmonary embolization on arterial stiffening and right
      ventricular function in dogs.
AB  - Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter
      pulmonary artery (PA) stiffness. The response of the RV to an acute increase in
      pulmonary pressure is unclear. In addition, the relation between total pulmonary
      arterial compliance and local PA stiffness has not been investigated. We used a
      combination of right heart catheterization (RHC) and magnetic resonance imaging
      (MRI) to assess PA stiffening and RV function in dogs before and after acute
      embolization. We hypothesized that in moderate, acute PH the RV is able to
      compensate for increased afterload, maintaining adequate coupling. Also, we
      hypothesized that in the absence of PA remodeling the relative area change in the
      proximal PA (RAC, a noninvasive index of local area strain) correlates with the
      total arterial compliance (stroke volume-to-pulse pressure ratio). Our results
      indicate that, after embolization, RV function is able to accommodate the demand
      for increased stroke work without uncoupling, albeit at the expense of a
      reduction of efficiency. In this acute model, RAC showed excellent correlation
      with total arterial compliance. We used this correlation to assess PA pulse
      pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We
      demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably
      close to measurements from RHC. These results, if confirmed in chronic PH and
      clinically, suggest that monitoring of PH progression by noninvasive methods may
      be possible.

PMID- 22864866
TI  - Design of antimicrobial stewardship care bundles on the high dependency unit.
AB  - BACKGROUND: Antimicrobial guidelines aim to optimise treatment and minimise
      development of resistance. Care bundles support the implementation of local
      guidelines. OBJECTIVE: Pharmacist identification of where in the prescribing,
      monitoring and documentation process, the quality of antimicrobial management in
      a High Dependency Unit of a large teaching hospital could be improved and design
      of antimicrobial care bundles for initiation and de-escalation of therapy to
      standardise care and improve practice. SETTING: This study was conducted in a 10
      bed, mixed medical-surgical HDU in a large Scottish (UK) teaching hospital.
      METHODS: Quality indicators (n = 30) were agreed through multidisciplinary team
      review with reference to the evidence base, national strategy and local policy.
      Adherence to these quality indicators was measured before and after the
      pharmacist's contributions. Areas of non-adherence to quality indicators were
      used to design the care bundles. MAIN OUTCOME MEASURE: Adherence to the quality
      indicators before and after the pharmacist's action. Categorisation of
      pharmaceutical care issues ('check', 'change in drug therapy' and 'change in drug
      therapy process') were quantified. RESULTS: From 134 prescriptions, the
      pharmacist undertook 1,447 actions to ensure adherence to the 30 indicators.
      Adherence was very good (85.3 % CI 83.5, 87.1), but would have been
      unsatisfactory (53.5 % CI 50.9, 56.1) without the pharmacist's action (p <
      0.001). Change in drug therapy process or change in drug therapy initiated by the
      pharmacist accounted for 31.9 % (CI 29.5, 34.3) of adherence. Non-adherence was
      related to documentation of past allergic reactions, bacteriological specimen
      results, indication and length of course of treatment (both at initiation and de
      escalation). Care bundles were designed to target areas of non-adherence to local
      guidelines. CONCLUSION: The pharmacist made a significant contribution to
      improving adherence to evidence based antimicrobial prescribing quality
      indicators agreed by the multidisciplinary team. Prompts have been identified
      from the pharmaceutical care process and applied in the design of two
      antimicrobial care bundles proposed to support adherence with antimicrobial
      prescribing policies and guidelines.

PMID- 22864867
TI  - Inappropriate prescribing in hospitalised Australian elderly as determined by the
      STOPP criteria.
AB  - BACKGROUND: The elderly population is increasing worldwide. Due to age-related
      physiological changes that affect the pharmacokinetics and pharmacodynamics of
      drugs, the elderly are predisposed to adverse drug reactions. Prescribing of
      potentially inappropriate medications (PIMs) has been found to be prevalent among
      the elderly and PIM use has been associated with hospitalisations and mortality.
      OBJECTIVES: This study aims to identify the prevalence and nature of pre
      admission inappropriate prescribing by using the STOPP (screening tool of older
      people's prescriptions) criteria amongst a sample of hospitalised elderly
      inpatients in South Australia. SETTING: Medical, surgical and rehabilitation
      wards of a public teaching hospital in Adelaide, South Australia. MAIN OUTCOME
      MEASURE: Pre-admission prevalence of PIM. METHOD: Medication management plans of
      100 patients of >=65 years old were prospectively studied to determine the
      prevalence of pre-admission PIM use. Sixty-five criteria of STOPP were applied to
      identify PIMs. RESULTS: The total number of pre-admission medications screened
      during the study period was 949; the median number of medicines per patient was
      nine (range 2-28). Overall the STOPP criteria identified 138 PIMs in 60 % of
      patients. The most frequently encountered PIM was opiates prescribed in patients
      with recurrent falls (12.3 %), followed by benzodiazepines in fallers (10.1 %)
      and proton pump inhibitors when prescribed for peptic ulcer disease for long-term
      at maximum doses (9.4 %). The number of medications were found to have a positive
      correlation with pre-admission PIM use (r(s) = 0.49, P < 0.01). CONCLUSIONS: Pre
      admission PIM use is highly prevalent among the studied population. Strategies to
      reduce PIM use should be undertaken by physicians and pharmacists. The use of the
      STOPP criteria in clinical practice to reduce prescriptions of inappropriate
      medications requires further investigation.

PMID- 22864868
TI  - Prevalence, seriousness and effect of previous adverse drug reactions on
      prescribing during acute medical admission.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are associated with significant
      morbidity, mortality and cost. Knowledge of the prevalence of previous ADRs at
      admission highlights the potential burden of ADR risks to hospital in-patients.
      However, the proportion of acute medical admissions with previous ADRs and how
      this affects inpatient prescribing is uncertain. OBJECTIVES: To determine the
      prevalence and seriousness of previous ADRs in newly admitted medical patients,
      and ascertain the effect of previous ADRs on choice of prescribed medications
      during acute hospitalisation. Also, we compared the seriousness of ADRs as
      classified by patients and standard definition. SETTING: Acute admissions within
      the medical directorate of a district general hospital serving a population of
      about 280,000 people in the north east of England. METHOD: Newly admitted medical
      patients over a period of 8 weeks were prospectively screened to identify those
      with a previous history of ADR using patient interviews. Reviews of hospital
      notes and general practice summaries were undertaken for patients we were unable
      to interview. A structured form was used to collect relevant data from patients
      identified to have previous ADRs from the aforementioned sources. MAIN OUTCOME
      MEASURES: Prevalence and seriousness of previous ADRs, and the proportion of
      acute medical prescriptions affected by previous ADRs. RESULTS: A total of 509
      acute admissions were screened. Of these, 19.8 % had ADRs to previously
      prescribed medications. Whereas 62.7 % of patients deemed their ADRs to be
      serious, only 20.9 % of previous ADRs were so by standard definition. 18.8 % of
      previous ADRs affected choice of prescribed medications during the present
      admission but this was not influenced by the seriousness of previous ADRs.
      CONCLUSION: The prevalence of previous ADRs at admission is high and
      significantly affects choice of drugs used during acute hospitalisation. There
      are clear inconsistencies between patient perspective and standard definition of
      the seriousness of ADRs which is likely to be due to patients' heightened
      subjective perception of harm.

PMID- 22864869
TI  - Interpatch foraging in honeybees-rational decision making at secondary hubs based
      upon time and motivation.
AB  - For honeybees, Apis mellifera, the hive has been well known to function as a
      primary decision-making hub, a place from which foragers decide among various
      directions, distances, and times of day to forage efficiently. Whether foraging
      honeybees can make similarly complex navigational decisions from locations away
      from the hive is unknown. To examine whether or not such secondary decision
      making hubs exist, we trained bees to forage at four different locations.
      Specifically, we trained honeybees to first forage to a distal site "CT" 100 m
      away from the hive; if food was present, they fed and then chose to go home. If
      food was not present, the honeybees were trained to forage to three auxiliary
      sites, each at a different time of the day: A in the morning, B at noon, and C in
      the afternoon. The foragers learned to check site CT for food first and then
      efficiently depart to the correct location based upon the time of day if there
      was no food at site CT. Thus, the honeybees were able to cognitively map
      motivation, time, and five different locations (Hive, CT, A, B, and C) in two
      spatial dimensions; these are the contents of the cognitive map used by the
      honeybees here. While at site CT, we verified that the honeybees could choose
      between 4 different directions (to A, B, C, and the Hive) and thus label it as a
      secondary decision-making hub. The observed decision making uncovered here is
      inferred to constitute genuine logical operations, involving a branched
      structure, based upon the premises of motivational state, and spatiotemporal
      knowledge.

PMID- 22864870
TI  - Green and black tea intake in relation to prostate cancer risk among Singapore
      Chinese.
AB  - PURPOSE: Tea is one of the most commonly consumed beverages worldwide. To date,
      observational data from prospective cohort studies investigating the relationship
      between green and black tea intake and prostate cancer risk are sparse and
      equivocal. In a population-based, prospective cohort study of Chinese men in
      Singapore, we investigated the relationship between green and black tea intake
      and prostate cancer risk. METHODS: Tea consumption data for 27,293 men were
      collected at baseline (between 1993 and 1998) using a validated food frequency
      questionnaire. After an average of 11.2 years of follow-up, 298 men had developed
      prostate cancer. Proportional hazards regression methods were used to assess the
      associations between tea intake and prostate cancer risk. RESULTS: There was no
      association between daily green tea intake and prostate cancer risk, compared
      with no green tea intake [hazard ratio (HR) = 1.08; 95 % confidence interval (CI)
      0.79, 1.47]. For black tea, a statistically significant positive association and
      trend were observed for daily intake compared with no black tea intake (HR =
      1.41, 95 % CI 1.03, 1.92; p for trend <0.01) CONCLUSIONS: Few prospective data
      are available from populations that have both a high level and wide range of
      black and green tea intake; this study represents a unique opportunity to
      evaluate their individual effects on prostate cancer risk. Our findings support
      the notion that green tea intake does not protect against prostate cancer and
      that black tea intake may increase prostate cancer risk.

PMID- 22864871
TI  - Adhesion and proliferation of human osteoblast-like cells on different
      biodegradable implant materials used for graft fixation in ACL-reconstruction.
AB  - INTRODUCTION: This study investigates the adhesion and proliferation behaviour of
      human osteoblast-like cells over time when incubated on surfaces of biodegradable
      screws and pins used for graft fixation in ACL reconstruction. MATERIALS AND
      METHODS: 2 mm-sized-wedges of four bioresorbable implants [1. poly-L-lactide acid
      (PLLA) screw, 2. PLLA/beta-tricalciumphosphate (PLLA/TCP) (70 %/30 %) screw, 3.
      poly-L-lactide-co-glycolic acid/beta-tricalciumphosphate (PLGA/TCP) (70 %/30 %)
      screw and 4. PLLA pin] were incubated with human osteoblast-like cells. All
      probes were evaluated after 3,7,14 and 21 days by cell number count,
      determination of cell proliferation, observation of cell adhesion of human
      osteoblast-like cells under an environmental scanning electron microscope (ESEM),
      and by a live-dead assay. RESULTS: Cell numbers were lower at all stages in both
      PLLA groups compared to the composite materials (PLLA/TCP and PLGA/TCP). A
      significant difference in cell proliferation was found after 21 days. The cells
      on both composite screws (PLLA/TCP and PLGA/TCP) maintained more contact points
      with the screw surface compared to the cells on PLLA screws under ESEM. No
      cytotoxicity could be observed in the live-dead assay. DISCUSSION: Mainly, beta
      TCP as part of a composite implant seems to offer good ultrastructural properties
      for cell adhesion according to our in vitro study. Cell numbers seem to be
      influenced by the degradation behaviour with higher cell numbers in the composite
      groups.

PMID- 22864873
TI  - Influence of counterions on the structure of bis(oxazoline)copper(II) complexes;
      an EPR and ENDOR investigation.
AB  - X- and Q-band EPR and ENDOR spectroscopy was used to study the structure of a
      series of heteroleptic and homoleptic copper bis(oxazoline) complexes, based on
      the (-)-2,2'-isopropylidenebis[(4S)-4-phenyl-2-oxazoline] ligand and bearing
      different counterions (chloride versus triflate); labelled [Cu(II)(1a-c)]. The
      geometry of the two heteroleptic complexes, [Cu(II)(1a)] and [Cu(II)(1c)],
      depended on the choice of counterion. Formation of the homoleptic complex was
      only evident when the Cu(II)(OTf)(2) salt was used (Cu(II)(Cl)(2) inhibited the
      transformation from heteroleptic to homoleptic complexes). The hyperfine and
      quadrupole parameters for the surrounding ligand nuclei were determined by ENDOR.
      Well resolved (19)F and (1)H couplings confirmed the presence of both coordinated
      water and TfO(-) counterions in [Cu(1a)].

PMID- 22864872
TI  - Iron overload signature in chrysotile-induced malignant mesothelioma.
AB  - Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among
      the commercially used types of asbestos (chrysotile, crocidolite, and amosite),
      the carcinogenicity of chrysotile is not fully appreciated. Here, we show that
      all three asbestos types similarly induced MM in the rat peritoneal cavity and
      that chrysotile caused the earliest mesothelioma development with a high fraction
      of sarcomatoid histology. The pathogenesis of chrysotile-induced mesothelial
      carcinogenesis was closely associated with iron overload: repeated administration
      of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction,
      significantly reduced the period required for carcinogenesis; massive iron
      deposition was found in the peritoneal organs with high serum ferritin; and
      homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most
      frequent genomic alteration in human MM and in iron-induced rodent
      carcinogenesis, was observed in 92.6% of the cases studied with array-based
      comparative genomic hybridization. The induced rat MM cells revealed high
      expression of mesoderm-specific transcription factors, Dlx5 and Hand1, and showed
      an iron regulatory profile of active iron uptake and utilization. These data
      indicate that chrysotile is a strong carcinogen when exposed to mesothelia,
      acting through the induction of local iron overload. Therefore, an intervention
      to remove local excess iron might be a strategy to prevent MM after asbestos
      exposure.

PMID- 22864874
TI  - A phase 1 study of vinflunine in combination with trastuzumab for the treatment
      for HER2-positive metastatic breast cancer.
AB  - OBJECTIVE: To determine the recommended dose (RD) of vinflunine in combination
      with trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive
      metastatic breast cancer (MBC) and to investigate potential pharmacokinetic (PK)
      interactions. PATIENTS AND METHODS: In the first part of the study, two dose
      levels of vinflunine given every 3 weeks were explored (280 and 320 mg/m(2))
      combined with trastuzumab (4 mg/kg loading dose and 2 mg/kg weekly). For each
      level of dose, six patients were enrolled to determine the RD for phase 2 studies
      (RP2S). In the second part of the study, 18 additional patients at RP2S have been
      evaluated to confirm safety and investigate preliminary antitumor activity.
      RESULTS: The RD was 320 mg/m(2) according to the dose escalation plan. Eleven of
      15 additional patients who received this dose experienced dose-limiting
      toxicities, leading to a reduction in the RD to 280 mg/m(2). When compared to
      prior trials when vinflunine was used as a single agent, neither vinflunine total
      blood clearance nor trastuzumab serum concentrations were modified when the drugs
      were combined. All patients were evaluable, and the overall response rate was
      73.3 % (95 % CI 54.1-87.7). The median progression-free survival was 11.3 months
      (95 % CI 9.4-21.0). At the dose of 280 mg/m(2), grade 3-4 neutropenia were seen
      in 4 patients (44.4 %) without febrile neutropenia. Non-hematologic grade 4
      toxicities were not reported while grade 3 peripheral sensory neuropathy
      concerned 2 patients (22.2 %). CONCLUSION: The RD of vinflunine in combination
      with the standard regimen of trastuzumab is 280 mg/m(2) every 3 weeks. No mutual
      PK drug-drug interaction was seen. This regimen appears to be active with a
      favorable safety profile. Its role in HER2-positive MBC treatment needs to be
      defined in prospective comparative clinical trials.

PMID- 22864875
TI  - Use of low-dose combined therapy with gemcitabine and paclitaxel for advanced
      urothelial cancer patients with resistance to cisplatin-containing therapy: a
      retrospective analysis.
AB  - PURPOSE: The prognosis of patients with advanced and recurrent urothelial cancer
      (UC) is poor. Although cisplatin (CDDP)-containing chemotherapy is the most
      effective regimen in these patients, there is no other established
      chemotherapeutic regimen. We administered combination therapy with low-dose
      gemcitabine (GEM) and paclitaxel (PTX), named low-dose gemcitabine-paclitaxel (LD
      GP) therapy, as salvage therapy for these patients. The aim was to evaluate the
      anti-tumoral effects, relief of pain, and toxicity of LD-GP therapy in patients
      with resistance to CDDP-containing therapy. PATIENTS AND METHODS: Thirty-five
      patients with advanced UC, previously treated with CDDP-containing regimens, were
      treated with LD-GP therapy (GEM, 700 mg/m(2) + PTX, 70 mg/m(2) on day 1 and 8,
      repeated every 28 days). Pain was measured on a visual analog scale before and
      after treatment. Pain relief and survival were compared between this and other
      treatment regimens. RESULTS: None of the patients had complete response to LD-GP
      therapy. Partial response and stable disease were seen in 25.7 and 62.9 % of
      patients, respectively. Kaplan-Meier curves showed better survival in patients
      with LD-GP therapy than with others (p = 0.034). Twenty-eight patients (80.0 %)
      had adequate pain relief, and only two patients needed to increase their
      analgesics. Other regimens demonstrated pain relief in 30.4 % of patients. Common
      toxicities included leukopenia, with five patients requiring granular colony
      stimulating factor therapy (14.3 %). The most common non-hematologic toxicity was
      fatigue (n = 7, 17.1 %). CONCLUSIONS: LD-GP therapy is feasible and well
      tolerated as salvage therapy in patients with advanced UC with resistance to CDDP
      containing therapy.

PMID- 22864876
TI  - Phase I study of the Aurora B kinase inhibitor barasertib (AZD1152) to assess the
      pharmacokinetics, metabolism and excretion in patients with acute myeloid
      leukemia.
AB  - PURPOSE: Barasertib (AZD1152) is a pro-drug that rapidly undergoes phosphatase
      mediated cleavage in serum to release barasertib-hQPA, a selective Aurora B
      kinase inhibitor that has shown preliminary activity in clinical studies of
      patients with acute myeloid leukemia (AML). The pharmacokinetic (PK), metabolic
      and excretion profiles of barasertib and barasertib-hQPA were characterized in
      this open-label Phase I study. METHODS: Five patients with poor prognosis AML
      (newly diagnosed, relapsed or refractory) received barasertib 1,200 mg as a 7-day
      continuous infusion every 28 days. On Day 2 of Cycle 1 only, patients also
      received a 2-hour infusion of [(14)C]-barasertib. Blood, urine and feces samples
      were collected at various time points during Cycle 1. Safety and preliminary
      efficacy were also assessed. RESULTS: Barasertib-hQPA was extensively distributed
      to tissues, with a slow rate of total clearance (CL = 31.4 L/h). Overall, 72-82 %
      of radioactivity was recovered, with approximately double the amount recovered in
      feces (mean = 51 %) compared with urine (mean = 27 %). The main metabolism
      pathways for barasertib were (1) cleavage of the phosphate group to form
      barasertib-hQPA, followed by oxidation and (2) loss of the fluoroaniline moiety
      to form barasertib-hQPA desfluoroaniline, followed by oxidation. One of the four
      patients evaluable for response entered complete remission. No new or unexpected
      safety findings were observed; the most common adverse events were nausea and
      stomatitis. CONCLUSIONS: The PK profile of barasertib is similar to previous
      studies using the same dosing regimen in patients with AML. The majority of
      barasertib-hQPA clearance occurred via hepatic metabolic routes.

PMID- 22864877
TI  - Cholera models with hyperinfectivity and temporary immunity.
AB  - A mathematical model for cholera is formulated that incorporates hyperinfectivity
      and temporary immunity using distributed delays. The basic reproduction number
      R(0) is defined and proved to give a sharp threshold that determines whether or
      not the disease dies out. The case of constant temporary immunity is further
      considered with two different infectivity kernels. Numerical simulations are
      carried out to show that when R(0) > 1, the unique endemic equilibrium can lose
      its stability and oscillations occur. Using cholera data from the literature, the
      quantitative effects of hyperinfectivity and temporary immunity on oscillations
      are investigated numerically.

PMID- 22864878
TI  - Evidence-based decisions for local and systemic wound care (Br J Surg 2012; 99:
      1172-1183).

PMID- 22864879
TI  - Randomized clinical trial of open hepatectomy with or without intermittent
      Pringle manoeuvre (Br J Surg 2012; 99: 1203-1209).

PMID- 22864880
TI  - Randomized clinical trial of endoluminal locoregional resection versus
      laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant
      therapy.
AB  - BACKGROUND: In selected patients with early low rectal cancer, locoregional
      excision combined with neoadjuvant therapy may be an alternative treatment option
      to total mesorectal excision (TME). METHODS: This prospective randomized trial
      compared endoluminal locoregional resection (ELRR) by transanal endoscopic
      microsurgery versus laparoscopic TME in the treatment of patients with small non
      advanced low rectal cancer. Patients with rectal cancer staged clinically as cT2
      N0 M0, histological grade G1-2, with a tumour less than 3 cm in diameter, within
      6 cm of the anal verge, were randomized to ELRR or TME. All patients underwent
      long-course neoadjuvant chemoradiotherapy. RESULTS: Fifty patients in each group
      were analysed. Overall tumour downstaging and downsizing rates after neoadjuvant
      chemoradiotherapy were 51 and 26 per cent respectively, and were similar in both
      groups. All patients had R0 resection with tumour-free resection margins. At long
      term follow-up, local recurrence had developed in four patients (8 per cent)
      after ELRR and three (6 per cent) after TME. Distant metastases were observed in
      two patients (4 per cent) in each group. There was no statistically significant
      difference in disease-free survival (P = 0.686). CONCLUSION: In selected
      patients, ELRR had similar oncological results to TME. Unique Protocol ID: URBINO
      LEZ-1995; registration number: NCT01609504 (http://www.clinicaltrials.gov).

PMID- 22864881
TI  - Randomized clinical trial of robot-assisted versus standard laparoscopic right
      colectomy.
AB  - BACKGROUND: Robotic surgery was invented to overcome the demerits of laparoscopic
      technique. However, it is unclear whether robot-assisted colectomy (RAC) has
      significant clinical advantages over laparoscopically assisted colectomy (LAC) in
      treating colonic cancer. The aim of this study was to compare the surgical
      outcomes of RAC versus LAC for right-sided colonic cancer. METHODS: Patients with
      right-sided colonic cancer were randomized to receive RAC or LAC. The primary
      outcome measure was length of hospital stay. Secondary outcomes were duration of
      operation, morbidity, postoperative pain, hospital costs and pathological quality
      of the specimen. RESULTS: Of 71 patients randomized, 70 (35 in each group) were
      included in the analysis. Hospital stay, surgical complications, postoperative
      pain score, resection margin clearance and number of lymph nodes harvested were
      similar in both groups. The duration of surgery was longer in the RAC group (195
      versus 130 min; P < 0.001). No conversion to open surgery was needed in either
      group. Overall hospital costs were significantly higher for RAC (US $ 12,235
      versus $ 10,320; P = 0.013); the higher costs were attributed primarily to the
      costs of surgery, including consumables. CONCLUSION: Robotic-assisted
      laparoscopic right colectomy was feasible but provided no benefit to justify the
      greater cost. REGISTRATION NUMBER: NCT01042743 (http://www.clinicaltrials.gov).

PMID- 22864882
TI  - Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma.
AB  - BACKGROUND: The study was undertaken to determine prognostic factors and the
      value of systematic lymphadenectomy on survival in sporadic gastrinoma. METHODS:
      Patients with sporadic gastrinoma who underwent initial surgery during a 21-year
      period in two tertiary referral centres were analysed retrospectively with
      respect to clinical characteristics, operative procedures and outcome. RESULTS:
      Forty-eight patients with a median age of 52 (range 22-73) years were analysed.
      Some 18 patients had pancreatic and 26 had duodenal gastrinomas, whereas the
      primary tumour remained unidentified in four patients. After a median
      postoperative follow-up of 83 (range 3-296) months, 20 patients had no evidence
      of disease, 13 patients were alive with disease, 11 patients had died from the
      disease and four had died from unrelated causes. In 41 patients who underwent
      potentially curative surgery, systematic lymphadenectomy with excision of more
      than ten lymph nodes resulted in a higher rate of biochemical cure after surgery
      than no or selective lymphadenectomy (13 of 13 versus 18 of 28 patients; P =
      0.017), with a trend towards prolonged disease specific survival (P = 0.062) and
      disease-free survival (P = 0.120), and a reduced risk of death (0 of 13 versus 7
      of 24 patients; P = 0.037). Negative prognostic factors for disease specific
      survival were pancreatic location (P = 0.029), tumour size equal to or larger
      than 25 mm (P = 0.003), Ki-67 index more than 5 per cent (P < 0.001),
      preoperative gastrin level 3000 pg/ml or more (P = 0.003) and liver metastases (P
      < 0.001). Sex, age, type of surgery and presence of lymph node metastases had no
      influence on disease free or disease specific survival. CONCLUSION: In sporadic
      gastrinoma, systematic lymphadenectomy during initial surgery may reduce the risk
      of persistent disease and improve survival.

PMID- 22864883
TI  - Impact of lymphadenectomy on survival in surgery for sporadic gastrinoma (Br J
      Surg 2012; 99: 1234-1240).

PMID- 22864884
TI  - Laparoscopic stapled cardioplasty for failed treatment of achalasia.
AB  - BACKGROUND: Treatment of primary achalasia includes injection of botulinum toxin,
      pneumatic dilatation or surgical myotomy. All of these procedures have an
      associated failure rate. Laparoscopic stapled cardioplasty (LSC) may be an
      alternative to failed pneumatic dilatation and laparoscopic Heller's myotomy
      where oesophagectomy has previously been the only surgical option. METHODS:
      Selected patients with recurrent achalasia following multiple failed medical
      treatments, including myotomies, were managed by LSC. Patients had postoperative
      contrast swallows before discharge with clinical follow-up. RESULTS: All seven
      patients treated with LSC were discharged within 5 days. Rapid oesophageal
      emptying was noted on all post-LSC contrast swallows. No patient had an
      anastomotic leak. After 1 year, all but one patient was free from dysphagia, all
      had gained weight, and four patients had heartburn controlled by a proton pump
      inhibitor. CONCLUSION: LSC may be a useful procedure for resistant achalasia.

PMID- 22864885
TI  - Real-time computed tomography-based augmented reality for natural orifice
      transluminal endoscopic surgery navigation.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is
      technically challenging owing to endoscopic short-sighted visualization,
      excessive scope flexibility and lack of adequate instrumentation. Augmented
      reality may overcome these difficulties. This study tested whether an image
      registration system for NOTES procedures (IR-NOTES) can facilitate navigation.
      METHODS: In three human cadavers 15 intra-abdominal organs were targeted
      endoscopically with and without IR-NOTES via both transgastric and transcolonic
      routes, by three endoscopists with different levels of expertise. Ease of
      navigation was evaluated objectively by kinematic analysis, and navigation
      complexity was determined by creating an organ access complexity score based on
      the same data. RESULTS: Without IR-NOTES, 21 (11.7 per cent) of 180 targets were
      not reached (expert endoscopist 3, advanced 7, intermediate 11), compared with
      one (1 per cent) of 90 with IR-NOTES (intermediate endoscopist) (P = 0.002).
      Endoscope movements were significantly less complex in eight of the 15 listed
      organs when using IR-NOTES. The most complex areas to access were the pelvis and
      left upper quadrant, independently of the access route. The most difficult organs
      to access were the spleen (5 failed attempts; 3 of 7 kinematic variables
      significantly improved) and rectum (4 failed attempts; 5 of 7 kinematic variables
      significantly improved). The time needed to access the rectum through a
      transgastric approach was 206.3 s without and 54.9 s with IR-NOTES (P = 0.027).
      CONCLUSION: The IR-NOTES system enhanced both navigation efficacy and ease of
      intra-abdominal NOTES exploration for operators of all levels. The system
      rendered some organs accessible to non-expert operators, thereby reducing one
      impediment to NOTES procedures.

PMID- 22864886
TI  - Non-operative management of acute cholecystitis in the elderly (Br J Surg 2012;
      99: 1254-1261).

PMID- 22864887
TI  - Effect of specialist decision-making on treatment strategies for colorectal liver
      metastases.
AB  - BACKGROUND: One hundred and ten patients were treated with palliative
      chemotherapy, of whom 53 had liver-only disease and had not been reviewed by a
      specialist liver surgeon. One scan was excluded as all reviewers felt it to be of
      insufficient quality to assess. Improved surgical technique and better
      chemotherapeutic manipulation of metastatic disease has increased the number of
      patients eligible for potentially curative resection of colorectal liver
      metastases. The rapid evolution in this field suggests that non-specialist
      decision-making may lead to inappropriate management. This study aimed to assess
      the management of colorectal liver metastases by non-liver surgeons. METHODS: All
      patients who underwent chemotherapy with palliative intent for metastatic
      colorectal cancer at a regional oncology centre between 1 January and 31 December
      2009 were identified from a prospectively maintained local database. Six
      resectional liver surgeons blinded to patient management and outcome reviewed
      pretreatment imaging and assigned each scan a score based on their own management
      choice. A consensus decision was reached on the appropriateness of palliative
      chemotherapy. RESULTS: One hundred and ten patients were treated with palliative
      chemotherapy, of whom 53 had liver-only disease and had not been reviewed by a
      specialist liver surgeon. One scan was excluded as all reviewers felt it to be of
      insufficient quality to assess [corrected]. Tumours in 33 patients (63 per cent)
      were considered potentially resectable, with a high level of interobserver
      agreement (kappa = 0 . 577). When individual approach to management was
      considered, interobserver agreement was less marked (kappa = 0 . 378).
      CONCLUSION: Management of patients with colorectal liver metastases without the
      involvement of a specialist liver multidisciplinary team can lead to patients
      being denied potentially curative treatments. Management of these patients must
      involve a specialist liver surgeon to ensure appropriate management.

PMID- 22864888
TI  - Effect of specialist decision-making on treatment strategies for colorectal liver
      metastases (Br J Surg 2012; 99: 1263-1269).

PMID- 22864889
TI  - Repeat hepatic resection for colorectal liver metastases.
AB  - BACKGROUND: Some 75-80 per cent of patients undergoing liver resection for
      colorectal liver metastases develop intrahepatic recurrence. A significant number
      of these can be considered for repeat liver surgery. This study examined the
      outcomes of repeat liver resection for the treatment of recurrent colorectal
      metastases confined to the liver. METHODS: Patients who underwent repeat liver
      resection in a single tertiary referral hepatobiliary centre were identified from
      a database. Clinicopathological variables were analysed to assess factors
      predictive of survival. RESULTS: A total of 195 patients underwent repeat
      resection between 1993 and 2010. Median age was 63 years, and the median interval
      between first and repeat resection was 13.8 months. Thirty-three patients (16.9
      per cent) underwent completion hemihepatectomy or extended hemihepatectomy and
      the remainder had non-anatomical or segmental resection. The 30-day mortality
      rate was 1.5 per cent, and the overall 30-day morbidity rate was 20.0 per cent.
      Overall 1-, 3- and 5-year survival rates were 91.2, 44.3 and 29.4 per cent
      respectively. Tumour size 5 cm or greater was the only independent predictor of
      overall survival (relative risk 1.71, 95 per cent confidence interval 1.08 to
      2.70; P = 0.021). Neoadjuvant chemotherapy before resection, perioperative blood
      transfusion, bilobar disease, R1 resection margin and multiple metastases were
      among factors that did not significantly influence survival. CONCLUSION: Repeat
      hepatic resection remains the only curative option for patients presenting with
      recurrent colorectal liver metastases.

PMID- 22864890
TI  - Intraoperative portal venous pressure and long-term outcome after curative
      resection for hepatocellular carcinoma.
AB  - BACKGROUND: Outcomes of liver resection for hepatocellular carcinoma (HCC) have
      improved owing to better surgical techniques and patient selection. Portal
      hypertension may influence outcome but the preoperative definition and role of
      portal hypertension are far from clear. The aim of this study was to elucidate
      the influence of portal venous pressure (PVP) measured directly during surgery on
      outcomes of liver resection in patients with HCC. METHODS: Patients who had
      resection of HCC between 1997 and 2009, and who underwent direct measurement of
      PVP immediately after laparotomy were enrolled. These patients were divided into
      groups with high (at least 20 cmH(2)O) and low (less than 20 cmH(2)O) PVP. The
      influence of PVP on overall and recurrence-free survival was analysed and
      prognostic factors were identified. RESULTS: A total of 177 patients were
      enrolled, 129 in the low-PVP group and 48 in the high-PVP group. The 5-year
      overall survival rate (63.7 versus 31 per cent; P < 0.001) and recurrence-free
      survival rate (52.5 versus 12 per cent; P < 0.001) were significantly higher in
      patients with low PVP. In multivariable analysis, two or more tumours, tumour
      diameter at least 5 cm, high PVP, grade B liver damage and Hepatic Activity Index
      (HAI) grade 7 or more were significant predictors of poorer survival after liver
      resection. Two or more tumours, tumour diameter at least 5 cm and HAI grade 7 or
      more were significant predictors of poorer recurrence-free survival. CONCLUSION:
      High PVP was associated with poor long-term outcome after liver resection for
      HCC.

PMID- 22864891
TI  - Role of patient-specific virtual reality rehearsal in carotid artery stenting.
AB  - BACKGROUND: Recent advances in simulation science permit patient-specific
      rehearsal of endovascular stenting procedures. This study aimed to evaluate how
      effectively real interventions are replicated by patient-specific rehearsal
      technology, and to assess its value as a preparatory tool for the
      interventionalist and the operating team. METHODS: All patients deemed candidates
      for carotid artery stenting procedures with suitable computed tomography images
      were enrolled. Each team member rehearsed the virtual procedure in the
      laboratory, simulated operating theatre or angiography suite environment
      immediately before treating the real patient. Dexterity and qualitative metrics
      were recorded. Subjective questionnaires used a Likert scale from 1 (poor) to 5
      (excellent). RESULTS: Of 18 patients, three were excluded. In 11 of 15 and 13 of
      15 patients respectively endovascular tool use and fluoroscopy angles were
      identical during rehearsal and the real procedure. In a third of patients, the
      simulator did not adequately predict difficulties in cannulating the stenotic
      internal or common carotid arteries. The procedure realism, value in evaluating
      the case, increase in efficiency in tool use, and potential to increase
      communication, confidence and team performance were all rated highly (4 of 5).
      CONCLUSION: Patient-specific rehearsal was rated highly for both face and content
      validity. Access strategy, endovascular material use and angiographic imaging
      were all replicated effectively, although certain biomechanical vessel properties
      seemed to be replicated to a lesser degree. Patient-specific rehearsal
      constitutes a unique tool that may help tailor endovascular material choice, and
      optimize the preoperative preparation of the interventionalist and team.

PMID- 22864893
TI  - Rapid on-site evaluation of axillary fine-needle aspiration cytology in breast
      cancer (Br J Surg 2012; 99: 807-812).

PMID- 22864895
TI  - P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis (Br
      J Surg 2012; 99: 246-255).

PMID- 22864897
TI  - Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in
      distinguishing between benign and invasive intraductal papillary mucinous
      neoplasm of the pancreas (Br J Surg 2011; 98: 104-110).

PMID- 22864899
TI  - False feedback increases detection of low-prevalence targets in visual search.
AB  - Many critical search tasks, such as airport and medical screening, involve
      searching for targets that are rarely present. These low-prevalence targets are
      associated with extremely high miss rates Wolfe, Horowitz, & Kenner (Nature, 435,
      439-440, 2005). The inflated miss rates are caused by a criterion shift, likely
      due to observers attempting to equate the numbers of misses and false alarms.
      This equalizing strategy results in a neutral criterion at 50 % target
      prevalence, but leads to a higher proportion of misses for low-prevalence
      targets. In the present study, we manipulated participants' perceived number of
      misses through explicit false feedback. As predicted, the participants in the
      false-feedback condition committed a higher number of false alarms due to a
      shifted criterion. Importantly, the participants in this condition were also more
      successful in detecting targets. These results highlight the importance of
      perceived prevalence in target search tasks.

PMID- 22864900
TI  - [Medical examination: Preparation for ENT specialisation: Part 6].

PMID- 22864902
TI  - [Surgery of the external ear canal].
AB  - Diseases of the external ear canal are a frequent reason for consulting the
      otolaryngologist. Conservative treatment is sufficient in most cases. Chronic
      problems of the external ear canal, however, sometimes require surgical
      treatment. Enlargement of the external ear canal as well as the entrance of the
      external ear canal are often simultaneously performed together with
      tympanoplasties, in order to obtain good access to the middle ear and to
      facilitate postoperative care. In this review, we focus on surgical techniques
      for different pathologies such as exostosis, stenosis, fibrosis, and tumors of
      the external ear canal.

PMID- 22864901
TI  - [S1 Clinical guideline"adenoids and adenoidectomy"].
AB  - On behalf of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery,
      a clinical guideline for adenoids and adenoidectomy was developed in 5 consensus
      meetings after taking into consideration the current literature. This guideline
      was released by the presidium on 13 April 2011. Anatomy, pathology and
      pathophysiology, symptoms, diagnosis, therapy, and course are presented.

PMID- 22864903
TI  - Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular
      cell injury by suppressing reactive oxygen species generation via reducing
      receptor for AGEs (RAGE) expression.
AB  - Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in
      tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been
      shown to ameliorate tubular injury both in cell culture and diabetic animal
      model. However, effects of metformin on AGEs-induced tubular cell apoptosis and
      damage remain unknown. We examined here whether and how metformin could block the
      AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was
      evaluated by real-time reverse-transcription polymerase chain reactions. Reactive
      oxygen species (ROS) generation was measured with dihydroethidium staining.
      Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs
      upregulated RAGE mRNA levels and subsequently increased ROS generation and
      intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and
      transforming growth factor-beta gene expression in human renal proximal tubular
      cells, all of which were significantly blocked by the treatment of 0.01 and 0.1
      mM metformin. Compound C, an inhibitor of AMP-activated protein kinase
      significantly blocked the effects of metformin on RAGE gene expression and ROS
      generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently
      inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin
      completely suppressed the pro-apoptotic effects of AGEs in 2 different assay
      systems. Our present study suggests that metformin could inhibit the AGEs-induced
      apoptosis and inflammatory and fibrotic reactions in tubular cells probably by
      reducing ROS generation via suppression of RAGE expression through AMP-activated
      protein kinase activation. Metformin may protect against tubular cell injury in
      diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

PMID- 22864904
TI  - The influence of intensive physical training on salivary adipokine levels in
      Elite Rhythmic Gymnasts.
AB  - Exercise challenges homeostasis and establishes a new dynamic equilibrium. Elite
      Rhythmic Gymnasts (RG's) begin exercise at an early age, undergo physical and
      psychological stress, and adopt negative energy balance to retain a lean
      physique. The aim of the present study was to evaluate the effect of negative
      energy balance, acute and chronic exercise on salivary adiponectin, resistin and
      visfatin levels and their interaction with salivary cortisol, and insulin levels
      in elite RG's. This study is unique in character, as all variables were assessed
      on the field of competition. The study included 51 elite RG's participating in
      "Kalamata 2010 World Cup" in Kalamata, Greece on April 2010. Twenty-seven healthy
      age-matched girls were used as controls. Anthropometric values were assessed;
      baseline and post exercise salivary cortisol, insulin, adiponectin, resistin, and
      visfatin levels were measured. Comparisons regarding hormonal features between
      RG's and controls were adjusted for BMI and body fat percentage. Salivary
      adiponectin levels were higher (p<0.05) and visfatin lower (p=0.094) in RG's
      compared with controls, while no significant changes were observed regarding
      salivary cortisol, insulin, and resistin levels. In elite RG's acute intensive
      anaerobic exercise led to increased salivary insulin levels (p<0.001), reduced
      salivary adiponectin (p<0.001) and visfatin levels (p<0.05), and no changes in
      salivary resistin levels. Moreover, diurnal variation of salivary cortisol was
      lost. In elite RG's salivary adiponectin is upregulated and salivary visfatin is
      downregulated after chronic intensive exercise and negative energy balance, while
      both salivary adiponectin and visfatin levels are suppressed after short term
      intensive anaerobic exercise.

PMID- 22864905
TI  - Resistance of sperm motility to serum testosterone in men with excessive
      erythrocytosis at high altitude.
AB  - Excessive erythrocytosis (EE) [hemoglobin (Hb) >21 g/dl] observed in natives at
      high altitude (HA) seems to be due to elevated serum testosterone levels compared
      with men without EE at HA. The aim of the study was to determine the association
      between serum testosterone levels and high hemoglobin levels at HA with sperm
      quality. The study was conducted with 72 adult men living at 4,340 m and 52
      native men at sea level (SL). At HA, men were grouped according to hemoglobin
      value (group 1:16-21 g/dl or group 2: Hb >21 g/dl). Hemoglobin and serum
      testosterone levels were evaluated. Sperm concentration, percentage of
      progressive sperm motility, percentage of normal sperm morphology, and markers of
      seminal vesicles function (corrected seminal fructose) and of prostate function
      (seminal zinc levels) were calculated. Serum testosterone levels were
      significantly higher in the group with EE (p<0.001). Progressive sperm motility
      in men with EE was lower than in the other group (Hb >16-21 g/dl) and that of
      those at SL. Seminal pH, zinc levels and normal sperm morphology in men at HA
      were lower than at SL. At HA, a significant inverse relationship was observed
      between hemoglobin and progressive sperm motility (p<0.01). At SL, serum
      testosterone levels were directly related with progressive sperm motility,
      whereas at HA, no association was observed (p>0.05). No association between
      testosterone levels and corrected seminal fructose was observed in men with EE.
      In conclusion, low sperm motility was observed in men with EE despite elevated
      serum testosterone levels suggesting a resistance of sperm motility.

PMID- 22864906
TI  - Study of the involvement of pancreastatin in the physiopathology of diabetes
      mellitus associated with nonsecreting pituitary adenomas.
AB  - Pancreastatin, derived from chromogranin A, inhibits insulin and stimulates
      glucagon secretion in rodents. Immunohistochemistry localised pancreastatin in
      human pancreatic islet cells and gonadotroph pituitary cells. Nonsecreting
      pituitary adenomas, frequently associated with diabetes mellitus, arise quasi
      constantly from gonadotroph cells. We evaluated the possible involvement of
      pancreastatin in the physiopathology of diabetes mellitus associated with
      nonsecreting pituitary adenomas. Plasma pancreastatin levels were measured by
      radioimmunoassay in 5 groups of subjects: 10 patients with nonsecreting pituitary
      adenomas associated with diabetes mellitus (group I), 10 patients with
      nonsecreting pituitary adenomas without diabetes (Group II), 10 patients with
      ACTH or GH-secreting pituitary adenomas and diabetes mellitus (Group III), 10
      diabetic patients without pituitary adenomas (Group IV), and 10 healthy controls
      (Group V). Kidney and liver functions were normal in all of them and no patient
      was treated with a proton pump inhibitor. All pituitary adenomas were trans
      sphenoidally removed. Immunohistochemistry against pancreastatin was performed in
      5 patients of each of the 3 groups of pituitary adenomas. Plasma pancreastatin
      levels were not different between the different groups: 182+/-46 pg/ml (Group I),
      195+/-57 pg/ml (Group II), 239+/-42 pg/ml (Group III), 134+/-31 pg/ml, (Group
      IV), and 122+/-29 pg/ml (Group V). In contrast, they were significantly (p<0.05)
      higher before (391+/-65 pg/ml) than after trans-sphenoidal surgery (149+/-18
      pg/ml) without post-surgical change in diabetes. An immunostaining against
      pancreastatin was found in a majority of pituitary adenomas, associated or not
      with diabetes mellitus. These results argue against a role of pancreastatin in
      the pathogenesis of diabetes mellitus associated with nonsecreting pituitary
      adenomas.

PMID- 22864907
TI  - Expression patterns of 17beta-hydroxysteroid dehydrogenase 14 in human tissues.
AB  - 17betaHSD enzymes catalyze the stereospecific oxidation/reduction at carbon
      17beta of androgens and estrogens, and are important players in intracrine sex
      hormone synthesis. The biological relevance of 17betaHSD14, first named retSDR3,
      is largely unknown. We generated and validated an antibody targeting the
      17betaHSD14 antigen and used this for immunohistochemical evaluation of
      expression patterns in 33 healthy human tissues. Furthermore, sex steroid
      conversional activity in HSD17B14 overexpressing HEK293 and MCF10A cells was
      investigated by assessing interconversion products of estrone, estradiol,
      androstenedione, testosterone, and dehydroepiandrosterone. Immunohistochemical
      staining patterns of 17betaHSD14 with the enzyme being primarily expressed in
      glandular epithelial tissue reveal an enzyme with possible implications in the
      secretion or conversion of externally derived compounds. A role for 17betaHSD14
      in sex steroid metabolism is supported by the finding that 17HSD14 oxidizes both
      estradiol and testosterone into less bioactive steroid metabolites estrone and
      androstenedione, respectively.

PMID- 22864908
TI  - Facile TMSOTf-catalyzed preparation of 2-deoxy alpha-O-aryl-D-glycosides from
      glycosyl acetates.
AB  - 2-Deoxy alpha-O-aryl glycosides were conveniently obtained by reaction of 2-deoxy
      glycosyl acetates with phenols in the presence of TMSOTf as the promoter. The
      current method provides the O-aryl glycosides with good to excellent yields, and
      sole alpha selectivity.

PMID- 22864909
TI  - qRT-PCR: a method and its difficulties.

PMID- 22864910
TI  - Systemic exposure to Pseudomonal bacteria: a potential link between type 1
      diabetes and chronic inflammation.
AB  - Bacterial endotoxins have been associated with chronic inflammation and the
      development and progression of diabetic nephropathy. We hypothesized that
      subjects with high serum lipopolysaccharide activity also carry remains of
      bacterial DNA in their system. Serum-derived bacterial DNA clones were isolated
      and identified from 10 healthy controls and 14 patients with type 1 diabetes
      (T1D) using universal primers targeted to bacterial 16S rDNA. A total of 240
      clones representing 35 unique bacterial species were isolated and identified. A
      significant proportion of the isolated bacteria could be assigned to our living
      environment. Proteobacteria was by far the most prevalent phylum among the
      samples. Notably, the patients had significantly higher frequencies of
      Stenotrophomonas maltophilia clones in their sera compared to the healthy
      controls. Real-time PCR analysis of S. maltophilia and Pseudomonas aeruginosa
      flagellin gene copy number in the human leukocyte DNA fraction revealed that the
      overall Pseudomonal bacterial load was higher in older patients with T1D. Serum
      IgA- and IgG-antibody levels against Pseudomonal bacteria Delftia acidovorans, P.
      aeruginosa, and S. maltophilia were also determined in 200 healthy controls and
      200 patients with T1D. The patients had significantly higher serum levels of IgA
      antibodies against all three Pseudomonal bacteria. Additionally, the IgA
      antibodies against Pseudomonal bacteria correlated significantly with serum C
      reactive protein. These findings indicate that recurrent or chronic Pseudomonal
      exposure may increase susceptibility to chronic inflammation in patients with
      T1D.

PMID- 22864912
TI  - The earliest modern human colonization of Europe.

PMID- 22864911
TI  - Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the
      mitochondrial cristae.
AB  - We used electron cryotomography of mitochondrial membranes from wild-type and
      mutant Saccharomyces cerevisiae to investigate the structure and organization of
      ATP synthase dimers in situ. Subtomogram averaging of the dimers to 3.7 nm
      resolution revealed a V-shaped structure of twofold symmetry, with an angle of 86
      degrees  between monomers. The central and peripheral stalks are well resolved.
      The monomers interact within the membrane at the base of the peripheral stalks.
      In wild-type mitochondria ATP synthase dimers are found in rows along the highly
      curved cristae ridges, and appear to be crucial for membrane morphology. Strains
      deficient in the dimer-specific subunits e and g or the first transmembrane helix
      of subunit 4 lack both dimers and lamellar cristae. Instead, cristae are either
      absent or balloon-shaped, with ATP synthase monomers distributed randomly in the
      membrane. Computer simulations indicate that isolated dimers induce a plastic
      deformation in the lipid bilayer, which is partially relieved by their side-by
      side association. We propose that the assembly of ATP synthase dimer rows is
      driven by the reduction in the membrane elastic energy, rather than by direct
      protein contacts, and that the dimer rows enable the formation of highly curved
      ridges in mitochondrial cristae.

PMID- 22864913
TI  - Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.
AB  - Vertebrate Hedgehog (Hh) signals involved in development and some forms of
      cancer, such as basal cell carcinoma, are transduced by the primary cilium, a
      microtubular projection found on many cells. A critical step in vertebrate Hh
      signal transduction is the regulated movement of Smoothened (Smo), a seven
      transmembrane protein, to the primary cilium. To identify small molecules that
      interfere with either the ciliary localization of Smo or ciliogenesis, we
      undertook a high-throughput, microscopy-based screen for compounds that alter the
      ciliary localization of YFP-tagged Smo. This screen identified 10 compounds that
      inhibit Hh pathway activity. Nine of these Smo antagonists (SA1-9) bind Smo, and
      one (SA10) does not. We also identified two compounds that inhibit ciliary
      biogenesis, which block microtubule polymerization or alter centrosome
      composition. Differential labeling of cell surface and intracellular Smo pools
      indicates that SA1-7 and 10 specifically inhibit trafficking of intracellular Smo
      to cilia. In contrast, SA8 and 9 recruit endogenous Smo to the cilium in some
      cell types. Despite these different mechanisms of action, all of the SAs inhibit
      activation of the Hh pathway by an oncogenic form of Smo, and abrogate the
      proliferation of basal cell carcinoma-like cancer cells. The SA compounds may
      provide alternative means of inhibiting pathogenic Hh signaling, and our study
      reveals that different pools of Smo move into cilia through distinct mechanisms.

PMID- 22864915
TI  - Consequences of chronic reduction of cortical inhibition.

PMID- 22864916
TI  - Effect of CC chemokine receptor 4 antagonism on the evolution of experimental
      autoimmune encephalomyelitis.

PMID- 22864914
TI  - Circadian changes in long noncoding RNAs in the pineal gland.
AB  - Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including
      regulation of expression of genes and chromosomes. Here, we present evidence that
      lncRNAs are involved in vertebrate circadian biology. Differential night/day
      expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which
      is the source of melatonin, the hormone of the night. Approximately one-half of
      these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to
      >100-fold daily rhythms indicate that, in most cases, the change results from
      neural stimulation from the central circadian oscillator in the suprachiasmatic
      nucleus (doubling time = 0.5-1.3 h). Light exposure at night rapidly reverses
      (halving time = 9-32 min) levels of some of these lncRNAs. Organ culture studies
      indicate that expression of these lncRNAs is regulated by norepinephrine acting
      through cAMP. These findings point to a dynamic role of lncRNAs in the circadian
      system.

PMID- 22864917
TI  - Perioperative hypertension: defining at-risk patients and their management.
AB  - Hypertension is an extremely pervasive condition that affects a large percentage
      of the world population. Although guidelines exist for the treatment of the
      patient with elevated blood pressure, there remains a paucity of literature and
      accepted guidelines for the perioperative evaluation and care of the patient with
      hypertension who undergoes either cardiac or noncardiac surgery. Of particular
      importance is defining the patients most vulnerable to complications and the
      indications for immediate and rapid antihypertensive treatment and/or
      cancellation of surgery to reduce these risks in each of the three perioperative
      settings: preoperative, intraoperative, and postoperative. This review also
      examines the parenteral antihypertensive medications most commonly administered
      in the perioperative setting.

PMID- 22864918
TI  - Tracking cell lineage and fate into cerebellar circuits.
AB  - Understanding how cells from different neuronal and glial lineages contribute to
      functional circuits has been complicated by the difficulty in tracking cells as
      they integrate into brain circuits. Sudarov et al. (J Neurosci 31(30):11055
      11069, 2011) used a powerful genetics-based lineage marking approach to birth
      date ventricular zone-derived cells in the mouse cerebellum. The authors use
      their novel tools to elucidate the spatial and temporal dynamics of how distinct
      ventricular zone lineages are generated and assemble into the cerebellar
      microcircuitry. In this journal club, we discuss and evaluate the author's major
      findings.

PMID- 22864919
TI  - Antiprotozoal activity of medicinal plants against Ichthyophthirius multifiliis
      in goldfish (Carassius auratus).
AB  - Ichthyophthiriasis is a widespread disease in aquaculture and causes mass
      mortalities of fish. The development of new antiprotozoal agents for the
      treatment of Ichthyophthirius multifiliis infections is of increasing interest.
      The aim of the present study was to investigate the efficacy of 30 medicinal
      plants against I. multifiliis. The results showed that the methanol extracts of
      Magnolia officinalis and Sophora alopecuroides displayed the highest
      antiprotozoal activity against theronts, with 4-h LC(50) values estimated to be
      2.45 and 3.43 mg L(-1), respectively. Concentrations of 2.5, 5.0, 10.0, and 20.0
      mg L(-1) of M. officinalis extracts resulted in tomont mortality of 9.7, 43.7,
      91.3, and 100% at 20 h, respectively. From 40 to 320 mg L(-1) of S. alopecuroides
      extracts, tomont mortality increased from 29.7 to 100%. Antiprotozoal efficacy
      against settled tomonts (2 and 10 h) was also applied; the results indicated that
      encysted I. multifiliis tomonts were less susceptible to these plant extract
      treatments. In vivo experiments demonstrated that high concentrations of M.
      officinalis and S. alopecuroides extracts could kill tomonts, and M. officinalis
      significantly reduced its reproduction (P < 0.05). These results suggested that
      the methanol extracts of M. officinalis and S. alopecuroides have the potential
      to be used as an eco-friendly approach for the control of I. multifiliis.

PMID- 22864920
TI  - Antiparasitic efficacy of piperine against Argulus spp. on Carassius auratus
      (Linn. 1758): in vitro and in vivo study.
AB  - Argulus are common aquatic ectoparasites that create one of the major threats to
      aquaculture due to absence of suitable therapy. Piperine, a bioactive component
      of Piper longum, has medicinal properties and acts as anti-inflammatory,
      antibacterial, and antifungal, considering eco-friendliness and cost
      effectiveness. The present study aimed to evaluate antiparasitic effect of
      piperine against an ectoparasite Argulus spp. on Carassius auratus. Artificial
      Argulus infection was carried out by cohabitation method, and the fishes were
      selected for in vivo study when intensity of Argulus infestation was observed to
      be 15-20 Argulus per fish. In vitro and in vivo studies were performed at
      different concentration 1.0 (T (1)), 3.0 (T (2)), 5.0 (T (3)), 7.0 (T (4)), and
      9.0 mg l(-1) (T (5)) of piperine solution to treat Argulus for 3 and 72 h,
      respectively. The acute toxicity test for piperine EC 97 % against goldfish was
      performed for 96 h. The 96 h median lethal concentration (LC(50)) for piperine
      was found to be 52.64 mg l(-1). In vitro effect of piperine solution led to 100 %
      mortality of Argulus at 9.0 mg l(-1) in 3 h whereas, under in vivo test, the 100
      % antiparasitic efficacy of piperine solution was found at 9.0 mg l(-1) in 48 h.
      The EC(50) for 48 h was 9.0 mg l(-1), and thus, therapeutic index is 5.8. The
      results revealed that piperine at a concentration of 9.0 mg l(-1) can be used as
      a potential natural agent for controlling Argulus parasite.

PMID- 22864922
TI  - Biocompatible polydopamine fluorescent organic nanoparticles: facile preparation
      and cell imaging.
AB  - Biocompatible fluorescent organic nanoparticles with tunable photoluminescence
      were prepared via the one-pot oxidation of polydopamine and subsequently utilized
      for cell imaging.

PMID- 22864921
TI  - MACH14: a multi-site collaboration on ART adherence among 14 institutions.
AB  - The integration of original data from multiple antiretroviral (ARV) adherence
      studies offers a promising, but little used method to generate evidence to
      advance the field. This paper provides an overview of the design and
      implementation of MACH14, a collaborative, multi-site study in which a large data
      system has been created for integrated analyses by pooling original data from 16
      longitudinal ARV adherence studies. Studies selected met specific criteria
      including similar research design and data domains such as adherence measured
      with medication event monitoring system, psychosocial factors related to
      adherence behavior, and virologic and clinical outcomes. The data system created
      contains individual data (collected between 1997 and 2009) from 2,860 HIV
      patients. Collaboration helped resolve the challenges inherent in pooling data
      across multiple studies, yet produced a data system with strong statistical power
      and potentially greater capacity to address key scientific questions than
      possible with single-sample studies or even meta-analytic designs.

PMID- 22864924
TI  - Homing in rocky intertidal fish. Are Lipophrys pholis L. able to perform true
      navigation?
AB  - Although navigation is common in many animals, only a few perform true
      navigation, meaning that they have the ability to return to a given place by
      relying on indirect cues obtained at the release site (i.e., by relying on
      information from a "map and compass" mechanism). The common intertidal fish,
      Lipophrys pholis, is thought to have homing abilities through a mechanism that
      primarily makes use of familiar landmarks (i.e., piloting). Anecdotal reports
      that individuals return to their home pools after release at unfamiliar sites
      suggest that L. pholis might use cues collected at the release site to find their
      way back (i.e., they might use map and compass information). Using a completely
      artificial setup, we tested the homing abilities of L. pholis as a function of
      age, sex, and familiarity with the release site. The findings showed that
      motivation for homing is present only in the adult phase and is independent of
      sex and/or familiarity with the release site. Moreover, adults released at a
      completely unfamiliar place oriented themselves in a direction roughly similar to
      that of their home pools. The fact that L. pholis were tested in a complete
      artificial environment means that hydrodynamic cues can be excluded as playing a
      role in this process and restricts the candidate options (e.g., magnetic cues).
      The ability to perform navigation based on a "map and compass" mechanism raises
      many interesting questions about the learning process, once these individuals
      have restricted home ranges during their lives. In vertebrate navigation, the
      cues used during the navigation process are a question of debate, and L. pholis
      offers an outstanding model to test hypotheses and ultimately provide answers.

PMID- 22864923
TI  - Genome-wide association study identifies TNFSF13 as a susceptibility gene for IgA
      in a South Chinese population in smokers.
AB  - IgA is an important factor in our immune system. There are many diseases
      associated with it, such as IgA nephropathy, IgA deficiency, and so on. In order
      to describe the relationship between the genes and the IgA level, we performed a
      genome-wide association study of serum IgA with 1,999 healthy Chinese men in the
      first stage and replicated on an independent Chinese sample with 1,496 subjects
      in the second stage. Association between each SNP with IgA was estimated by
      multivariate linear regression analysis conditioned on age and smoke. Haplotype
      analysis for the block around the top SNP was performed. In the first stage, one
      genomic locus was identified to be significantly associated with IgA. The loci is
      TNFSF13 (17p13.1; rs3803800; P = 6.26 * 10(-8)). In smoke-specific analysis,
      rs3803800 was approximately significantly associated with IgA levels in smokers
      (P = 3.96 * 10(-7)), while no association was observed in nonsmokers (P = 2.28 *
      10(-1)). In addition, we performed the haplotype analysis on chromosome 17 with
      the SNPs around rs3803800. Although the total P value for the haplotype did not
      acquire significant difference, three haplotypes (TGAG, CACG, and CACA) reached
      significant (P < 0.05). In conclusion, TNFSF13 could be a susceptible gene which
      was discovered having relationship with serum IgA level, and smoke might be a
      factor infecting the IgA level.

PMID- 22864925
TI  - LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular
      endothelial growth factor in human breast cancer cells and promotes angiogenesis.
AB  - Elevated serum or tissue levels of lectin galactoside-binding soluble 3 binding
      protein (LGALS3BP) have been associated with short survival and development of
      metastasis in a variety of human cancers. However, the role of LGALS3BP,
      particularly in the context of tumor-host relationships, is still missing. Here,
      we show that LGALS3BP knockdown in MDA-MB-231 human breast cancer cells leads to
      a decreased adhesion to fibronectin, a reduced transendothelial migration and,
      more importantly, a reduced expression of vascular endothelial growth factor
      (VEGF). Production of VEGF, that was restored by exposure of silenced cells to
      recombinant LGALS3BP, required an intact PI3k/Akt signaling. Furthermore, we show
      that LGALS3BP was able to directly stimulate HUVEC tubulogenesis in a VEGF
      independent, galectin-3-dependent manner. Immunohistochemical analysis of human
      breast cancer tissues revealed a correlation among LGALS3BP expression, VEGF
      expression, and blood vessel density. We propose that in addition to its
      prometastatic role, LGALS3BP secreted by breast cancer cells functions critically
      as a pro-angiogenic factor through a dual mechanism, i.e by induction of tumor
      VEGF and stimulation of endothelial cell tubulogenesis.

PMID- 22864926
TI  - ADRB2 G-G haplotype associated with breast cancer risk among Hispanic and non
      Hispanic white women: interaction with type 2 diabetes and obesity.
AB  - INTRODUCTION: Polymorphisms in the beta-2-adrenergic receptor (ADRB2) gene have
      been studied in relation to risk of type 2 diabetes and obesity, risk factors
      that have received increased attention in relation to breast cancer. We evaluated
      the hypothesis that ADRB2 variants (rs1042713, rs1042714) are associated with
      breast cancer risk in non-Hispanic white (NHW) and Hispanic (H) women using data
      from a population-based case-control study conducted in the southwestern United
      States. METHODS: Data on lifestyle and medical history, and blood samples, were
      collected during in-person interviews for incident primary breast cancer cases
      (1,244 NHW, 606 H) and controls (1,330 NHW, 728 H). ADRB2 genotypes for
      rs1042713(G/A) and rs1042714(G/C) were determined using TaqMan assays. The
      associations of each variant and corresponding haplotypes with breast cancer were
      estimated using multivariable logistic regression. RESULTS: Two copies compared
      to one or zero copies of the ADRB2 G-G haplotype were associated with increased
      breast cancer risk for NHW women [odds ratio (OR), 1.95; 95 % confidence interval
      (95 % CI), 1.26-3.01], but with reduced risk for H women [OR, 0.74; 95 % CI, 0.50
      1.09]. Effect estimates were strengthened for women with a body mass index (BMI)
      >=25 kg/m(2) [H: OR, 0.50; 95 % CI, 0.31-0.82; NHW: OR, 3.85; 95 % CI, 1.88-7.88]
      and for H women with a history of diabetes [H: OR, 0.32; 95 % CI, 0.12-0.89].
      CONCLUSIONS: These data suggest that ethnicity modifies the association between
      the ADRB2 G-G haplotype and breast cancer risk, and being overweight or obese
      enhances the divergence of risk between H and NHW women.

PMID- 22864928
TI  - Keeping it small: nanotechnology enables scientists to target cancer in new ways.

PMID- 22864927
TI  - Clusters of genes encoding fructan biosynthesizing enzymes in wheat and barley.
AB  - Fructans are soluble carbohydrates with health benefits and possible roles in
      plant adaptation. Fructan biosynthetic genes were isolated using comparative
      genomics and physical mapping followed by BAC sequencing in barley. Genes
      encoding sucrose:sucrose 1-fructosyltransferase (1-SST), fructan:fructan 1
      fructosyltransferase (1-FFT) and sucrose:fructan 6-fructosyltransferase (6-SFT)
      were clustered together with multiple copies of vacuolar invertase genes and a
      transposable element on two barley BAC. Intron-exon structures of the genes were
      similar. Phylogenetic analysis of the fructosyltransferases and invertases in the
      Poaceae showed that the fructan biosynthetic genes may have evolved from vacuolar
      invertases. Quantitative real-time PCR was performed using leaf RNA extracted
      from three wheat cultivars grown under different conditions. The 1-SST, 1-FFT and
      6-SFT genes had correlated expression patterns in our wheat experiment and in
      existing barley transcriptome database. Single nucleotide polymorphism (SNP)
      markers were developed and successfully mapped to a major QTL region affecting
      wheat grain fructan accumulation in two independent wheat populations. The
      alleles controlling high- and low- fructan in parental lines were also found to
      be associated in fructan production in a diverse set of 128 wheat lines. To the
      authors' knowledge, this is the first report on the mapping and sequencing of a
      fructan biosynthetic gene cluster and in particular, the isolation of a novel 1
      FFT gene from barley.

PMID- 22864932
TI  - Triple negative breast cancer is associated with an increased risk of residual
      invasive carcinoma after lumpectomy.
AB  - BACKGROUND: To assess the potential mechanisms that may underlie increased local
      failure in triple negative (TN) breast cancers, an analysis was performed of the
      risk of residual carcinoma after lumpectomy with correlation to pathologic
      factors, including molecular phenotype. METHODS: A review of pathologic specimens
      was performed for women with invasive breast cancer treated with lumpectomy
      followed by reexcision. Data were collected on age; tumor size, grade, and nodal
      stage; estrogen receptor, progesterone receptor, and human endothelial growth
      factor receptor 2 (Her2); extensive intraductal component; lymphovascular
      invasion; margins; and reexcision findings. Univariate and multivariate logistic
      regression analyses were performed to evaluate for associations between
      pathologic features of the lumpectomy specimen and reexcision findings. Molecular
      phenotypes were defined by conventionally used immunohistochemical pattern.
      RESULTS: Data were collected on 369 patients with breast cancer. The median age
      was 57 years, median tumor size was 1.5 cm, 36% had positive margins, 32% had
      positive lymph nodes, 73.5% had the luminal A subtype, 9.5% had the luminal B
      subtype, 4.5% were Her2-enriched, and 12.5% were TN. Overall, 32% of patients had
      invasive cancer in their reexcision specimens, and 51% of those with the TN
      subtype had residual invasive disease on reexcision compared with 30% to 31% for
      other subtypes. On univariate analysis, age, tumor size, margin status,
      lymphovascular invasion, nodal status, and TN subtype were associated with
      elevated risk of residual invasive cancer. On multivariate analysis using a
      forward stepwise model, TN subtype maintained significance, with an odds ratio of
      3.28 (P = .002). CONCLUSION: TN subtype has a statistically significant
      association with an increased risk of residual tumor. This suggests the putative
      increase in the risk of local failure in TN patients may be related to increased
      residual tumor burden.

PMID- 22864934
TI  - Differential cytotoxic response in keloid fibroblasts exposed to photodynamic
      therapy is dependent on photosensitiser precursor, fluence and location of
      fibroblasts within the lesion.
AB  - Treatment of keloid disease (KD) is ill-defined and remains challenging. We
      previously reported successful clinical application of photodynamic therapy (PDT)
      in KD. The aim here was to evaluate cytotoxic effect of PDT using methyl
      aminolevulinate (M-ALA) and 5-aminolevulinic acid (5-ALA) on keloid fibroblasts
      (KF) (n = 8) from different lesional sites (top, middle and margin) as compared
      to normal skin fibroblasts (n = 3). The effect of protoporphyrin IX (PpIX)
      precursors was evaluated by fluorescence emission, LDH and WST-1 assay, reactive
      oxygen species (ROS) generation and qRT-PCR analysis. Apoptosis/necrosis
      differentiation and senescence were studied by fluorometric staining with Hoechst
      33258/propidium iodide and beta-galactosidase activity, respectively. Three hours
      post incubation with 4 mM precursors of photosensitisers, PpIX accumulation was
      site specific and higher with M-ALA. Cytotoxicity was also site specific (higher
      in fibroblasts from middle of the keloid as compared to cells from other sites)
      and increased proportionately to fluence rates post-PDT. Additionally,
      cytoproliferation was significantly decreased post-PDT depending on the light
      energy. Fluorescence analysis revealed that M-ALA instigated higher KF
      cytotoxicity at lower fluence (<=20 J/cm(2)) while 5-ALA instigated higher KF
      cytotoxicity at higher fluence, except in cells derived from middle of the
      keloid. ROS-mediated cytotoxicity was light energy dependent. Senescence was not
      observed at higher light energies (>10 J/cm(2)). Compared to other sites,
      fibroblasts from the middle were more prone to cell death post 5-ALA treatment.
      We conclude that cytotoxicity post-PDT in KD fibroblasts is dependent on the
      lesional site, precursor of intracellular photosensitiser and fluence. Thus, PDT
      may be used for site-targeted therapy of KD.

PMID- 22864935
TI  - Invasive Aspergillus infection localized to the gastric wall: report of a case.
AB  - Invasive aspergillosis is most commonly seen in patients with immune disorders
      and usually in the lung. Local invasive aspergillosis of the gastrointestinal
      system is quite rare. A 13-year-old female without immune deficiency presented
      with acute abdomen due to full-thickness necrosis of the gastric fundus. The
      necrotic gastric wall was excised and the stomach repaired. The pathology
      revealed a gastric ulcer with invading Aspergillus hyphae and spores.
      Aspergillosis is an opportunistic infection and its spores cannot survive in the
      normal gastric mucosa. The Aspergillus spores in this case probably grew on a
      background of gastric ulcer and caused wall necrosis and that the surgical
      treatment possibly provided a cure because it remained localized to the gastric
      wall.

PMID- 22864933
TI  - Identification of novel germline polymorphisms governing capecitabine
      sensitivity.
AB  - BACKGROUND: Capecitabine, an oral 5-fluorouracil (5-FU) prodrug, is widely used
      in the treatment of breast, colorectal, and gastric cancers. To guide the
      selection of patients with potentially the greatest benefit of experiencing
      antitumor efficacy, or, alternatively, of developing toxicities, identifying
      genomic predictors of capecitabine sensitivity could permit its more informed
      use. METHODS: The objective of this study was to perform capecitabine sensitivity
      genome-wide association studies (GWAS) using 503 well genotyped human cell lines
      from individuals representing multiple different world populations. A meta
      analysis that included all ethnic populations then enabled the identification of
      novel germline determinants (single nucleotide polymorphisms [SNPs]) of
      capecitabine susceptibility. RESULTS: First, an intrapopulation GWAS of Caucasian
      individuals identified reference SNP 4702484 (rs4702484) (within adenylate
      cyclase 2 [ADCY2]) at a level reaching genome-wide significance (P = 5.2 * 10(-8)
      ). This SNP is located upstream of the 5 methyltetrahydrofolate-homocysteine
      methyltransferase reductase (MTRR) gene, and it is known that the enzyme for MTRR
      is involved in the methionine-folate biosynthesis and metabolism pathway, which
      is the primary target of 5-FU-related compounds, although the authors were unable
      to identify a direct relation between rs4702484 and MTRR expression in a tested
      subset of cells. In the meta-analysis, 4 SNPs comprised the top hits, which,
      again, included rs4702484 and 3 additional SNPs (rs8101143, rs576523, and
      rs361433) that approached genome-wide significance (P values from 1.9 * 10(-7) to
      8.8 * 10(-7) ). The meta-analysis also identified 1 missense variant (rs11722476;
      serine to asparagine) within switch/sucrose nonfermentable-related, matrix
      associated, actin-dependent regulator of chromatin (SMARCAD1), a novel gene for
      association with capecitabine/5-FU susceptibility. CONCLUSIONS: Toward the goal
      of individualizing cancer chemotherapy, the current study identified novel SNPs
      and genes associated with capecitabine sensitivity that are potentially
      informative and testable in any patient regardless of ethnicity.

PMID- 22864936
TI  - Prediction of true-negative lymph node metastasis in clinical IA non-small cell
      lung cancer by measuring standardized uptake values on positron emission
      tomography.
AB  - PURPOSE: We developed a method for predicting true-negative lymph node metastases
      in clinical IA non-small lung cancer (NSCLC) by the combined evaluation of
      computed tomography (CT), 2-[18F]-fluoro-2-deoxy-D-glucose positron emission
      tomography (FDG-PET) findings and the maximum standardized uptake value (SUVmax)
      of primary tumors. METHODS: The subjects of this study were 94 patients with
      clinical stage IA NSCLC who underwent both preoperative CT and FDG-PET. We
      analyzed the relationship between the SUVmax of primary tumors and various
      clinicopathological factors to find the best method available for assessing true
      negative lymph node metastasis. RESULTS: The pathological stages were IA (n =
      80), IB (n = 4), IIA (n = 5), IIIA (n = 4), and IV (n = 1). Pathologic lymph node
      metastasis was recognized in nine patients and the SUVmax of these tumors ranged
      from 3.3 to 20.3. A SUVmax of 3.0 was defined as the cut-off point and patients
      were dichotomized according to this point. Tumors with SUVmax of 3.0 or less were
      associated with a significantly lower incidence of pleural and vascular invasion
      and were characterized by the degree of differentiation. CONCLUSION: The SUVmax
      of primary tumors reflects the grade of malignancy; therefore, the combined
      evaluation of FDG-PET/CT findings with the SUVmax of primary tumors may help
      predict lymph node metastasis negativity.

PMID- 22864937
TI  - Totally laparoscopic pancreas-sparing duodenectomy.
AB  - Pancreas-sparing duodenectomy (PSD) is a practical surgical procedure for
      patients with duodenal adenoma, which is difficult to resect endoscopically. We
      describe how we performed a totally laparoscopic PSD to resect a duodenal adenoma
      in a 64-year-old woman, who had been referred for treatment of a 50-mm villous
      polypoid mass in the second portion of the duodenum. We performed end-to-side
      anastomosis between the common duct of the bile and pancreatic ducts and the
      jejunal limb intracorporeally following the duodenal resection. A biliary leak
      developed, but resolved spontaneously and the patient was discharged on
      postoperative day (POD) 32. The surgical margin was free of neoplastic change.
      Although there is limited experience and appropriate indications must await
      future studies, this case demonstrates that laparoscopic PSD is feasible, safe,
      and effective for selected patients.

PMID- 22864939
TI  - Fabrication of a multifunctional carbon nanotube "cotton" yarn by the direct
      chemical vapor deposition spinning process.
AB  - A continuous cotton-like carbon nanotube fiber yarn, consisting of multiple
      threads of high purity double walled carbon nanotubes, was fabricated in a
      horizontal CVD gas flow reactor with water vapor densification by the direct
      chemical vapor deposition spinning process. The water vapor interaction leads to
      homogeneous shrinking of the CNT sock-like assembly in the gas flow. This allows
      well controlled continuous winding of the dense thread inside the reactor. The
      CNT yarn is quite thick (1-3 mm), has a highly porous structure (99%) while being
      mechanically strong and electrically conductive. The water vapor interaction
      leads to homogeneous oxidation of the CNTs, offering the yarn oxygen
      functionalized surfaces. The unique structure and surface of the CNT yarn provide
      it multiple processing advantages and properties. It can be mechanically
      engineered into a dense yarn, infiltrated with polymers to form a composite and
      mixed with other yarns to form a blend, as demonstrated in this research.
      Therefore, this CNT yarn can be used as a "basic yarn" for various CNT based
      structural and functional applications.

PMID- 22864938
TI  - Dietary, lifestyle and clinicopathological factors associated with APC mutations
      and promoter methylation in colorectal cancers from the EPIC-Norfolk study.
AB  - The tumour suppressor APC is the most commonly altered gene in colorectal cancer
      (CRC). Genetic and epigenetic alterations of APC may therefore be associated with
      dietary and lifestyle risk factors for CRC. Analysis of APC mutations in the
      extended mutation cluster region (codons 1276-1556) and APC promoter 1A
      methylation was performed on 185 archival CRC samples collected from participants
      of the European Prospective Investigation into Cancer (EPIC)-Norfolk study, with
      the aim of relating these to high-quality seven-day dietary and lifestyle data
      collected prospectively. Truncating APC mutations (APC(+) ) and promoter 1A
      methylation (PM(+) ) were identified in 43% and 23% of CRCs analysed,
      respectively. Distal CRCs were more likely than proximal CRCs to be APC(+) or
      PM(+) (p = 0.04). APC(+) CRCs were more likely to be moderately/well
      differentiated and microsatellite stable than APC(-) CRCs (p = 0.05 and 0.03).
      APC(+) CRC cases consumed more alcohol than their counterparts (p = 0.01) and
      PM(+) CRC cases consumed lower levels of folate and fibre (p = 0.01 and 0.004).
      APC(+) or PM(+) CRC cases consumed higher levels of processed meat and iron from
      red meat and red meat products (p = 0.007 and 0.006). Specifically, CRC cases
      harbouring GC-to-AT transition mutations consumed higher levels of processed meat
      (35 versus 24 g/day, p = 0.04) and iron from red meat and red meat products (0.8
      versus 0.6 mg/day, p = 0.05). In a logistic regression model adjusted for age,
      sex and cigarette-smoking status, each 19 g/day (1SD) increment increase in
      processed meat consumption was associated with cases with GC-to-AT mutations (OR
      1.68, 95% CI 1.03-2.75). In conclusion, APC(+) and PM(+) CRCs may be influenced
      by diet and GC-to-AT mutations in APC are associated with processed meat
      consumption, suggesting a mechanistic link with dietary alkylating agents, such
      as N-nitroso compounds.

PMID- 22864940
TI  - Untethered 4,1,2-MC2B10 supraicosahedral metallacarboranes, their C,C'-dimethyl
      4,1,6-, 4,1,8- and 4,1,12-MC2B10 analogues, and DFT study of the (4,)1,2- to
      (4,)1,6-isomerisations of C2B11 carboranes and MC2B10 metallacarboranes.
AB  - Reduction of the tethered carborane 1,2-MU-(CH(2)SiMe(2)CH(2))-1,2-closo
      C(2)B(10)H(10) followed by metallation with {CpCo} or {(p-cymene)Ru} fragments
      affords both C,C'-dimethyl 4,1,2-MC(2)B(10) and 4,1,6-MC(2)B(10) species. DFT
      calculations indicate that the barriers to isomerisation of both 4-Cp-4,1,2-closo
      CoC(2)B(10)H(12) and 4-(eta-C(6)H(6))-4,1,2-closo-RuC(2)B(10)H(12) to their
      respective 4,1,6-isomers are too high for this to be the origin of the unexpected
      formation of 4,1,6-MC(2)B(10) products (in marked contrast to the related
      isomerisation of 1,2-closo-C(2)B(11)H(13) to 1,6-closo-C(2)B(11)H(13)), and,
      indeed, the 4,1,2-species are recovered unchanged from refluxing toluene.
      Equally, the DFT-calculated profile for the isomerisation of [7,8-nido
      C(2)B(10)H(12)](2-) to [7,9-nido-C(2)B(10)H(12)](2-) suggests that the unexpected
      formation of 4,1,6-metallacarboranes is unlikely to result from isomerisation of
      a reduced (nido) carborane following desilylation. Instead, the source of the
      4,1,6-MC(2)B(10) compounds is traced to desilylation of 1,2-MU
      (CH(2)SiMe(2)CH(2))-1,2-closo-C(2)B(10)H(10) by Li or Na prior to reduction. The
      supraicosahedral metallacarboranes 1,8-Me(2)-4-Cp-4,1,8-closo-CoC(2)B(10)H(10),
      1,12-Me(2)-4-Cp-4,1,12-closo-CoC(2)B(10)H(10) and 1,12-Me(2)-4-(p-cymene)-4,1,12
      closo-RuC(2)B(10)H(10) are also reported with all new species characterised both
      spectroscopically and crystallographically.

PMID- 22864941
TI  - Rosai-dorfman disease (sinus histiocytosis with massive lymphadenopathy) of the
      pancreas: third reported occurrence.

PMID- 22864942
TI  - Locally ablative non-surgical management of colo-rectal liver metastasis.
AB  - BACKGROUND: Liver is one of the commonest sites of metastasis in colorectal
      cancer patients. Solitary liver metastasis or oligometastasis are traditionally
      treated by surgical resection or chemotherapy. DISCUSSION: There may be a
      subgroup of these patients who are not suitable for surgery or chemotherapy due
      to various co-morbid factors. These patients can be treated by novel minimally
      invasive or noninvasive ablative techniques like interstitial brachytherapy,
      extracranial stereotactic radiotherapy, and radiofrequency ablation.

PMID- 22864943
TI  - Comparison of transoral power-assisted endoscopic adenoidectomy to curettage
      adenoidectomy.
AB  - INTRODUCTION: The aim of this prospective and randomized study was to compare
      patients who underwent curettage adenoidectomy (CA) or transoral power-assisted
      endoscopic adenoidectomy (PAEA) performed as isolated procedures by a single
      surgeon over a period of 7 years. The success of an adenoidectomy has been
      evaluated by assessing the amount of reduction in the adenoid size and the
      symptomatic improvement at the sixth postoperative month. METHODS: Patients'
      nasal airway obstruction was graded by the parents of the patient on a visual
      analog scale (VAS), with a range from 0 to 10, with grade 10 representing total
      obstruction. The ratio of the choanal opening obstructed by an adenoid mass was
      measured and expressed in percentages as representative of the adenoid size.
      Preoperative and 6-month postoperative adenoid sizes were compared. RESULTS:
      Fifty-three patients (CA group 27 patients/PAEA group 26 patients) completed the
      study. In the CA group, VAS score improved from the preoperative score of 8.63 +/
      0.88 to the 6-month score of 2.22 +/- 1.01 (P < 0.0001); and in the PAEA group,
      the preoperative VAS score of 8.69 +/- 0.84 improved to 2.08 +/- 1.05 in the same
      period (P < 0.0001). No statistical significance was found when VAS score
      improvements were compared (P = 0.4569). The average ratio of choanal opening
      obstructed by an adenoid mass improved from the preoperative ratio of 89.41% +/-
      6.48% to the 6-month ratio of 7.85% +/- 2.28% in the CA group; and the
      preoperative ratio of 90.19% +/- 6.95% in the PAEA group improved to 3.65% +/-
      1.38% after 6 months. The reduction of adenoid size was significantly superior in
      PAEA than CA (P < 0.0001). The operative time in PAEA was significantly shorter
      than that in CA (P < 0.0001). CONCLUSION: Although symptomatic improvement at the
      6-month follow-up is statistically indifferent, PAEA has been shown to be
      superior to CA with its superior performance in providing a near-total
      elimination of the adenoid mass in a shorter operating time.

PMID- 22864944
TI  - Memantine and dizocilpine interactions with antinociceptive or discriminative
      stimulus effects of morphine in rats after acute or chronic treatment with
      morphine.
AB  - RATIONALE: Memantine is a N-methyl-D-aspartic acid receptor (NMDAR) channel
      blocker that binds to dizocilpine sites and appears well tolerated during chronic
      use. Published studies suggest NMDAR antagonists prevent development of tolerance
      to effects of morphine by blocking NMDAR hyperactivation. OBJECTIVES: We sought
      to compare effects of memantine to those of the more frequently studied
      dizocilpine and to evaluate memantine as a potential adjunct to modify tolerance
      to mu-opioid receptor agonists. METHODS: Sprague-Dawley rats were trained to
      discriminate morphine (3.2 mg/kg) and saline under fixed ratio 15 schedules of
      food delivery. Potency and maximal stimulus or rate-altering effects of
      cumulative doses of morphine were examined 30 min after pretreatment with
      dizocilpine (0.032-0.1 mg/kg) or memantine (5-10 mg/kg) and after chronic
      treatment with combinations of dizocilpine or memantine and morphine, 10 mg/kg
      twice daily, for 6 to 14 days. Effects of dizocilpine or memantine on morphine
      antinociception were examined in a 55  degrees C water tail-withdrawal assay with
      drug treatments parallel to those in discrimination studies. RESULTS: Acutely,
      memantine attenuated while dizocilpine potentiated the stimulus and
      antinociceptive effects of morphine. Neither chronic dizocilpine nor memantine
      blocked tolerance to the stimulus effects of morphine. In contrast, combined
      treatment with dizocilpine (0.1 mg/kg) blocked tolerance to antinociceptive
      effects of lower (0.1~3.2 mg/kg) but not higher doses of morphine, whereas
      memantine did not block tolerance. CONCLUSIONS: Memantine and dizocilpine
      interacted differently with morphine, possibly due to different NMDAR binding
      profiles. The lack of memantine-induced changes in morphine tolerance suggests
      that memantine may not be a useful adjunct in chronic pain management.

PMID- 22864945
TI  - The effects of chronic food restriction on cue-induced heroin seeking in
      abstinent male rats.
AB  - RATIONALE AND OBJECTIVES: Previous research with an animal model of relapse has
      shown that acute food deprivation will reinstate extinguished drug seeking.
      Recent evidence with humans, however, suggests that chronic food restriction
      rather than acute food deprivation is related to increases in drug taking and
      relapse, emphasizing a need for an animal model to elucidate the neural
      mechanisms mediating the effects of chronic food restriction on drug seeking.
      Here we studied the effects of chronic food restriction during a period of
      abstinence on heroin seeking in rats. METHODS: Rats were trained to self
      administer heroin over 10 days (0.1 mg/kg/infusion; i.v.). Rats were then removed
      from the operant conditioning chambers and exposed to a mild food restriction
      (resulting in 10-15 % decrease in body weight) or given unrestricted access to
      food for 14 days while abstinent. The abstinence period was followed by a drug
      seeking test under extinction conditions. Subsequent experiments manipulated the
      length of restriction and test conditions. RESULTS: Rats that were food
      restricted throughout the abstinence period demonstrated a robust increase in cue
      induced heroin seeking compared to sated rats. Re-feeding prior to testing or
      decreasing the length of the food restriction period prevented the augmentation
      of drug seeking. CONCLUSIONS: A combination of chronic food restriction and a
      concurrent state of hunger appears to be necessary for an increase in cue-induced
      heroin seeking following abstinence. The procedure presented here may serve as a
      useful model to study the increased risk for relapse following dietary
      manipulations in abstinent subjects.

PMID- 22864946
TI  - Effect of D-amphetamine on emotion-potentiated startle in healthy humans:
      implications for psychopathy and antisocial behaviour.
AB  - RATIONALE: An emerging literature associates increased dopaminergic
      neurotransmission with altered brain response to aversive stimuli in humans. The
      direction of the effect of dopamine on aversive motivation, however, remains
      unclear, with some studies reporting increased and others decreased amygdala
      activation to aversive stimuli following the administration of dopamine agonists.
      Potentiation of the startle response by aversive foreground stimuli provides an
      objective and directional measure of emotional reactivity and is considered
      useful as an index of the emotional effects of different drugs. OBJECTIVE: We
      investigated the effects of two doses of D-amphetamine (5 and 10 mg), compared to
      placebo, for the first time to our knowledge, using the affect-startle paradigm.
      METHOD: The study employed a between-subjects, double-blind design, with three
      conditions: 0 mg (placebo), and 5 and 10 mg D-amphetamine (initially n =
      20/group; final sample: n = 18, placebo; n = 18, 5 mg; n = 16, 10 mg). After
      drug/placebo administration, startle responses (eyeblinks) to intermittent noise
      probes were measured during viewing of pleasant, neutral and unpleasant images.
      Participants' general and specific impulsivity and fear-related personality
      traits were also assessed. RESULTS: The three groups were comparable on
      personality traits. Only the placebo group showed significant startle
      potentiation by unpleasant, relative to neutral, images; this effect was absent
      in both 5- and 10-mg D-amphetamine groups (i.e. the same effect of D-amphetamine
      observed at different doses in different people). CONCLUSIONS: Our findings
      demonstrate a reduced aversive emotional response under D-amphetamine and may
      help to account for the known link between the use of psychostimulant drugs and
      antisocial behaviour.

PMID- 22864947
TI  - Safety and feasibility of adjuvant chemotherapy with S-1 for Korean patients with
      curatively resected advanced gastric cancer.
AB  - BACKGROUND: Adjuvant chemotherapy with S-1 was proven to be effective in Japanese
      patients with advanced gastric cancer curatively resected with D2 lymph node
      dissection. MATERIALS AND METHODS: We retrospectively evaluated the medical
      records of 305 patients with stage II, III or IV (M0) gastric cancer who had
      received adjuvant S-1 chemotherapy following curative gastrectomy with D2 lymph
      node dissection between October 2007 and December 2009. Adjuvant S-1 was
      administered at a dose of 40 mg/m(2) twice daily for 4 weeks followed by 2 weeks
      of rest, every 6 weeks for eight cycles. RESULTS: Of the 305 patients, 248 (81.3
      %) and 198 (64.9 %) completed four and eight cycles of adjuvant chemotherapy,
      respectively. The most common reasons for discontinuing treatment prior to the
      planned eight cycles were adverse events (n = 47, 15.4 %) and tumor recurrence (n
      = 28, 9.2 %). Sixty-five (21.3 %) patients required dose reduction due to adverse
      events. The most common grade 3/4 toxicities were neutropenia (n = 39, 12.8 %),
      diarrhea (n = 15, 4.9 %). Multivariate analysis showed that total gastrectomy
      [odds ratio (OR) 2.44; 95 % confidence interval (CI) 1.29-4.62, p = 0.006] was an
      independent risk factor for grade 3/4 hematologic toxicities, and age > 65 years
      (OR 2.60; 95 % CI 1.34-5.07, p = 0.005) was an independent risk factor for grade
      3 non-hematologic toxicities. CONCLUSIONS: Adjuvant chemotherapy with S-1 for 1
      year is safe and feasible in Korean patients. Age > 65 years and total
      gastrectomy are independent risk factors for severe adverse events caused by
      adjuvant S-1 chemotherapy.

PMID- 22864948
TI  - Characterizing the disposition, metabolism, and excretion of an orally active pan
      deacetylase inhibitor, panobinostat, via trace radiolabeled 14C material in
      advanced cancer patients.
AB  - PURPOSE: Elucidating the metabolic profile of anticancer agent panobinostat is
      essential during drug development. Disposition, metabolism, and excretion
      profiles were characterized using trace radiolabeled (14)C-panobinostat in four
      patients with advanced cancer. METHODS: Oral (14)C-panobinostat was administered
      and serial blood, plasma, and excreta samples were collected up to 7 days
      postdose for radioactivity and pharmacokinetic analyses. Metabolites in plasma
      and excreta were profiled using liquid chromatography (LC) with radiometric
      detection, and their structures elucidated using LC-tandem mass spectrometry.
      RESULTS: Radioactivity (>=87 %) was recovered in excreta within 7 days: 44-77 %
      dose recovery in feces and 29-51 % in urine. Circulating radioactivity was
      localized in plasma, with minor partitioning to blood. Minimal recovery in feces
      (<3.5 % of dose) suggested near-complete oral absorption. Maximum concentrations
      (median, 21.2 ng/mL; range, 13.4-41.5 ng/mL) were achieved within 1 h, and median
      (range) terminal half-life, apparent oral, and renal clearance was 30.7 h (27.6
      33.2 h), 209 L/h (114-248 L/h), and 3.20 L/h (2.4-5.5 L/h), respectively.
      Approximately 40 metabolites were circulating in plasma, with biotransformation
      occurring primarily at the hydroxamic acid side chain and ethyl-methyl indole
      moiety. Metabolites derived from modification of the hydroxamic acid side chain
      were inactive for deacetylase inhibition. CONCLUSIONS: Panobinostat and its
      metabolites were excreted in similar amounts through the kidneys and liver with
      good dose recovery. Panobinostat was rapidly absorbed and cleared primarily
      through metabolism. Over half of its clearance was attributed to non-CYP-mediated
      pathways. Thus, CYP-mediated drug-drug interactions with panobinostat are
      predicted to be minor.

PMID- 22864949
TI  - A phase II study of docetaxel plus nedaplatin in patients with metastatic non
      small-cell lung cancer.
AB  - PURPOSE: Nedaplatin is a cisplatin derivative, which has similar activity to
      cisplatin in non-small-cell lung cancer (NSCLC) when combined with vindesine, and
      causes less nausea/vomiting and nephrotoxicity compared with cisplatin. The aim
      of this study was to evaluate the efficacy and safety of combination chemotherapy
      with docetaxel plus nedaplatin in patients with metastatic NSCLC. METHODS:
      Patients with metastatic stage IIIB excluding locally advanced diseases or stage
      IV NSCLC were enrolled between March 2004 and March 2006. They were treated with
      docetaxel (60 mg/m(2)) and nedaplatin (80 mg/m(2)) on day 1 every 3-4 weeks until
      progression or intolerable toxicity for up to 4 cycles. RESULTS: Forty-four
      patients (mean age, 65 years; range, 40-79 years) received a total of 140
      treatment cycles. Responses could be assessed in all patients (complete response,
      0; partial response, 22; stable disease, 11; and progressive disease, 11).
      Response rate was 50.0 % (95 % confidence interval [CI], 35.2-64.8 %) with a
      disease control rate of 75.0 % (95 % CI, 62.2-87.8 %). A high response rate was
      achieved in patients with squamous cell carcinoma (66.7 %) compared with that in
      patients with adenocarcinoma (41.4 %). Median survival time from the start of the
      combination chemotherapy was 13.0 months, and the progression-free survival time
      was 7.4 months. Grade 3 or 4 hematologic toxicities included leukopenia (28.6 %)
      and neutropenia (61.4 %). Nonhematologic toxicities were mild. CONCLUSION: The
      combination of docetaxel plus nedaplatin was well tolerated and demonstrated
      potent activity in patients with metastatic NSCLC, particularly squamous cell
      carcinoma of the lung.

PMID- 22864950
TI  - [Glaucoma screening by means of pupil campimetry].
AB  - BACKGROUND: The aim of the study was to find out if pupillographic assessment of
      the visual field by means of pupil campimetry can identify glaucomatous visual
      field defects and as such be used for glaucoma screening purposes. PATIENTS AND
      METHODS: 20 patients with open angle glaucoma and 30 healthy persons were
      examined by means of pupil campimetry. All glaucoma patients had a glaucomatous
      visual field defect in at least one eye. The stimulus pattern consisted of 17
      white-light stimuli which were presented within the 30 degrees  visual field,
      particularly in the Bjerrum region. The stimulus diameter was 6 degrees . Each
      stimulus was presented for 200 ms and the interval between the stimuli was 1800
      ms. Three stimulus intensities (16.4 cd/m2; 27.1 cd/m2 and 40.5 cd/m2) were
      tested. The individual pupil light reaction (PLR) amplitudes at all examined
      locations in the visual field, their sums and partial sums were compared between
      both groups by the two-sided two-sample t test. The diagnostic performance of the
      method in glaucoma diagnosis was evaluated by ROC curves (receiver operating
      characteristics). RESULTS: The average PLR at all locations in the visual field
      was reduced in glaucoma patients compared to healthy persons. The sums of the PLR
      were reduced in glaucoma patients as well. Significant differences in the PLR
      were found especially in the central and paracentral visual fields. The best AUC
      values (area under the curve) were reached with the highest stimulus intensity,
      the highest AUC value overall was 0.769. CONCLUSION: Although the difference in
      PLR between glaucoma patients and the control group was significant, the reached
      AUC values fell short of being ideal for screening purposes. A surprising finding
      was that the most central pupil response was reduced by the same amount as that
      in the Bjerrum region.

PMID- 22864951
TI  - A "trimer of dimers"-based model for the chemotactic signal transduction network
      in bacterial chemotaxis.
AB  - The network that controls chemotaxis in Escherichia coli is one of the most
      completely characterized signal transduction systems to date. Receptor clustering
      accounts for characteristics such as high sensitivity, precise adaptation over a
      wide dynamic range of ligand concentrations, and robustness to variations in the
      amounts of intracellular proteins. To gain insights into the structure-function
      relationship of receptor clusters and understand the mechanism behind the high
      performance signaling, we develop and analyze a model for a single trimer of
      dimers. This new model extends an earlier model (Spiro et al. in Proc. Natl.
      Acad. Sci. 94:7263-7268, 1997) to incorporate the recent experimental findings
      that the core structure of receptor clusters is the trimer of receptor dimers. We
      show that the model can reproduce most of the experimentally-observed behaviors,
      including excitation, adaptation, high sensitivity, and robustness to parameter
      variations. In addition, the model makes a number of new predictions as to how
      the adaptation time varies with the expression level of various proteins involved
      in signal transduction. Our results provide a more mechanistically-based
      description of the structure-function relationship for the signaling system, and
      show the key role of the interaction among dimer members of the trimer in the
      chemotactic response of cells.

PMID- 22864952
TI  - Causation and causal inference for genetic effects.
AB  - Over the past three decades, substantial developments have been made on how to
      infer the causal effect of an exposure on an outcome, using data from
      observational studies, with the randomized experiment as the golden standard.
      These developments have reshaped the paradigm of how to build statistical models,
      how to adjust for confounding, how to assess direct effects, mediated effects and
      interactions, and even how to analyze data from randomized experiments. The
      congruence of random transmission of alleles during meiosis and the randomization
      in controlled experiments/trials, suggests that genetic studies may lend
      themselves naturally to a causal analysis. In this contribution, we will reflect
      on this and motivate, through illustrative examples, where insights from the
      causal inference literature may help to understand and correct for typical biases
      in genetic effect estimates.

PMID- 22864954
TI  - Variability analysis and the diagnosis, management, and treatment of sepsis.
AB  - Severe sepsis leading to organ failure is the most common cause of mortality
      among critically ill patients. Variability analysis is an emerging science that
      characterizes patterns of variation of physiologic parameters (e.g., vital signs)
      and is believed to offer a means for evaluating the underlying complex system
      producing those dynamics. Recent studies have demonstrated that variability of a
      variety of physiological parameters offers a novel means for helping diagnose,
      manage, and treat sepsis. The purpose of this literature review is to examine
      existing data regarding the use of variability analysis in patients suffering
      from sepsis and to highlight potential uses for variability in improving care for
      patients with sepsis. Recent articles published on heart rate, respiratory rate,
      temperature, and glucose variability are reviewed. The association between
      reduced heart rate and temperature variability and sepsis and its severity, the
      relationship between augmented glucose variability and mortality risk, and
      current uses of respiratory rate variability in critically ill patients will all
      be discussed. These findings represent early days in the understanding of
      variability alteration and its physiological significance; further research is
      required to understand and implement variability analyses into meaningful
      clinical decision support algorithms. Large, multicenter observational studies
      are needed to derive and validate the associations between variability and
      clinical events and outcomes in order to realize the potential of variability to
      change sepsis care and improve clinical outcomes.

PMID- 22864953
TI  - Pediatric sepsis: preparing for the future against a global scourge.
AB  - Sepsis is a leading cause of morbidity and mortality among children worldwide. As
      consensus statements emerge regarding early recognition and goal-directed
      management of sepsis, scrutiny should be given to the unique characteristics of
      sepsis in children. Pediatric patients are not small adults! Sepsis epidemiology,
      pathophysiology, and management strategy can vary significantly from those for
      adults. Herein, we describe the epidemiology of pediatric sepsis, in both
      resource-rich and resource-poor worlds, and discuss how the pathophysiology of
      pediatric sepsis differs from that for adults. We discuss the timeline of
      management of pediatric sepsis, studying how discoveries over the past 50 years
      have changed the way sepsis is treated. Finally, we discuss the future of
      pediatric sepsis. We focus on approaches that carry the most substantive impact
      on the global burden of disease.

PMID- 22864955
TI  - A right visual field advantage for visual processing of manipulable objects.
AB  - Information about object-associated manipulations is lateralized to left parietal
      regions, while information about the visual form of tools is represented
      bilaterally in ventral occipito-temporal cortex. It is unknown how lateralization
      of motor-relevant information in left-hemisphere dorsal stream regions may affect
      the visual processing of manipulable objects. We used a lateralized masked
      priming paradigm to test for a right visual field (RVF) advantage in tool
      processing. Target stimuli were tools and animals, and briefly presented primes
      were identical to or scrambled versions of the targets. In Experiment 1, primes
      were presented either to the left or to the right of the centrally presented
      target, while in Experiment 2, primes were presented in one of eight locations
      arranged radially around the target. In both experiments, there was a RVF
      advantage in priming effects for tool but not for animal targets. Control
      experiments showed that participants were at chance for matching the identity of
      the lateralized primes in a picture-word matching experiment and also ruled out a
      general RVF speed-of-processing advantage for tool images. These results indicate
      that the overrepresentation of tool knowledge in the left hemisphere affects
      visual object recognition and suggests that interactions between the dorsal and
      ventral streams occurs during object categorization.

PMID- 22864957
TI  - Using community surveys to inform the planning and implementation of
      environmental change strategies: participatory research in 12 Washington
      communities.
AB  - A number of studies have demonstrated the efficacy of environmental change
      strategies (ECS) in effecting community-level change on attitudes and behaviors
      related to underage drinking (Treno and Lee in Alcohol Res Health 26:35-40, 2002;
      Birckmayer et al. in J Drug Educ 34(2):121-153, 2004). Primary data collection to
      inform the design of these strategies, however, can be resource intensive and
      exceed the capacity of community stakeholders. This study describes the
      participatory planning and implementation of community-level surveys in 12
      diverse communities in the state of Washington. These surveys were conducted
      through collaborations among community volunteers and evaluation experts assigned
      to each community. The surveys were driven by communities' prevention planning
      needs and interests; constructed from collections of existing, field-tested items
      and scales; implemented by community members; analyzed by evaluation staff; and
      used in the design of ECS by community-level leaders and prevention
      practitioners. The communities varied in the content of their surveys, in their
      sampling approaches and in their data collection methods. Although these surveys
      were not conducted using traditional rigorous population survey methodology, they
      were done within limited resources, and the participatory nature of these
      activities strengthened the communities' commitment to using their results in the
      planning of their environmental change strategies.

PMID- 22864956
TI  - MHC class I of saltwater crocodiles (Crocodylus porosus): polymorphism and
      balancing selection.
AB  - Saltwater crocodiles are in high demand for the production of luxury fashion
      items. However, their susceptibility to disease incurs substantial losses and it
      is hoped to be able to genetically select these animals for disease resistance.
      So far, this has only been enabled by phenotypic selection. Investigating the
      major histocompatibility complex (MHC) could provide insight into the ability of
      an individual to respond to pathogens acting as a selective pressure on the host.
      Here, we assessed genetic diversity and a role of selection in shaping the
      diversity of MHC class I exon 3 among 42 saltwater crocodiles from nine river
      basins in the Northern Territory, Australia. We generated 640 sequences using
      cloning and sequencing methods and identified 43 MHC variants among them.
      Phylogenetic analyses clustered these variants into two major clades, which may
      suggest two gene lineages. We found the number of variants within an individual
      varying between one and seven, indicating that there are at least four gene loci
      in this species. Selection detection analyses revealed an elevated ratio of
      nonsynonymous to synonymous substitutions (mean = 1.152 per codon), suggesting
      balancing selection. Population differentiation analyses revealed that the MHC
      did not show structuring among the river basins, and there were some shared
      variants among them. This may be a result of possible gene flow and/or similar
      selection pressures among populations. These findings provide background
      knowledge to identify potential MHC markers, which could be used for selecting
      genetically variable individuals for future disease associations. All MHC class I
      exon 3 sequences reported in this paper were submitted to the GenBank database
      with following accession numbers: HQ008785-HQ008789, HQ008791-HQ008798, HQ008808
      HQ008815, HQ008824, HQ008826-HQ008830, HQ008835, HQ008839, HQ008842-HQ008850, and
      JX023536-JX023540.

PMID- 22864958
TI  - Battling discrimination and social isolation: psychological distress among Latino
      day laborers.
AB  - Day labor is comprised of predominately male and recent Latino immigrants, mainly
      from Mexico and Central America who work in an unregulated and informal market.
      Three-quarters of the day labor force is undocumented and live under the federal
      poverty threshold as work is seasonal and highly contingent on the weather and
      the local economy. However, in spite of their exposure to significant health
      risks, little is known about the impact of Latino day laborers' (LDLs) work and
      life conditions on their mental health. This mixed methods study extends the
      literature by using the minority stress theoretical model to examine the
      relationship between discrimination and social isolation as well as participant
      identified protective factors such as religiosity and sending remittances with
      psychological distress. A quantitative survey with 150 LDLs was conducted and was
      followed by a qualitative member checking focus group to extend upon the
      quantitative results as well as the minority stress model with the lived
      experiences of these immigrant workers. Results reveal implications for
      prevention efforts with this hard-to-reach and marginalized population.

PMID- 22864960
TI  - Proximal thoracic aortic diameter measurements at CT: repeatability and
      reproducibility according to measurement method.
AB  - AIM: To determine the variability in CT measurements of proximal thoracic aortic
      diameters obtained using double-oblique short axis and semiautomatic centerline
      analysis techniques. Institutional review board approval, with waiver of informed
      consent, was obtained for this HIPAA-compliant, retrospective study. Cardiac
      gated thoracic aortic CT scans were evaluated in 25 patients. Maximum aortic
      diameter measurements at the annulus, sinuses, sinotubular junction and ascending
      aorta were generated using double-oblique short axis and semiautomatic centerline
      analysis techniques. Intraobserver and interobserver variability and variability
      between techniques were assessed using the Wilcoxon signed rank test, Spearman's
      correlation coefficients and Bland-Altman plots. Mean intraobserver diameter
      differences using double oblique views ranged from -0.3 to 0.6 mm. The 95 %
      confidence interval for difference in diameters was +/-2.4 to +/-5.1 mm for
      radiologist #1 and +/-2.6 to +/-5.2 mm for radiologist #2, depending on location.
      Mean intraobserver diameter differences using centerline analysis ranged from 0.2
      to 2.3 mm, and the 95 % confidence interval for difference in diameters was +/
      2.0 to +/-4.6 mm, depending on location. Significant interobserver differences
      were seen for both double oblique views and centerline analysis. Measurements
      obtained using the two methods were strongly correlated (r = 0.81-0.99), although
      they were consistently larger using centerline analysis (95 % confidence
      interval, +/-1.8 to +/-3.2 mm). Although measurement variability of the proximal
      thoracic aorta was generally low using double oblique and centerline analysis
      techniques, differences of up to approximately 5 mm in diameter occurred within
      the 95 % confidence interval. Neither technique was clearly more reliable than
      the other.

PMID- 22864959
TI  - Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in
      human biliary tract cancer.
AB  - BACKGROUND: The early diagnosis of biliary tract cancer (BTC) remains
      challenging, and there are few effective therapies. This study investigated
      whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key
      regulator of cellular energy metabolism in proliferating cells, could play a role
      in the diagnosis and therapy of BTC. METHODS: Plasma and bile M2-PK
      concentrations were measured by enzyme-linked immunosorbent assay in 88 patients
      with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK
      expression was assayed in a BTC tissue array by immunohistochemistry. The role of
      M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines
      by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing
      techniques. RESULTS: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK
      for malignancy were significantly higher than those for plasma M2-PK and serum
      carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and
      correlated with microvessel density. M2-PK positivity was a significant
      independent prognostic factor by multivariable analysis. Transfection of M2-PK in
      a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas
      silencing in an M2-PK-positive cell line (TFK cells) decreased tumor nodule
      formation and cellular invasion. A significant increase in endothelial tube
      formation was noted when supernatants from M2-PK-transfected cells were added to
      an in vitro angiogenesis assay, whereas supernatants from silenced cells negated
      endothelial tube formation. CONCLUSIONS: Bile M2-PK is a novel tumor marker for
      BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA
      mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic
      target.

PMID- 22864961
TI  - The strain-encoded (SENC) MR imaging for detection of global right ventricular
      dysfunction in pulmonary hypertension.
AB  - The aim of this study was to explore whether the regional peak longitudinal (LS)
      and circumferential strains (CS) at the right ventricular (RV) free wall could be
      used to identify global RV dysfunction in relation to RV ejection fraction (RVEF)
      and plasma concentration of brain natriuretic peptide (BNP) in pulmonary
      hypertension (PH). A total of 37 consecutive patients diagnosed with PH and 13
      healthy control subjects were included. Fast strain encoded and routine cine MRI
      was performed. The LS and CS at three RV levels were quantified and their
      relations with RVEF and BNP were investigated. Receiver operating characteristic
      (ROC) analysis was employed to assess the diagnostic utility of strain encoded
      MRI for the detection of low RVEF. Significant correlations with LS were observed
      for RVEF and BNP. Compared to CS, LS showed better correlation with RVEF. The mid
      ventricular level of RV was the most sensitive site for evaluation of RV
      dysfunction. According to our ROC analysis, LS showed higher sensitivity and
      specificity to detect low RVEF. Compared to CS, LS showed stronger correlations
      with RVEF and BNP and could be a good detector of RV dysfunction in PH.

PMID- 22864962
TI  - An 'ameridelphian' marsupial from the early Eocene of Australia supports a
      complex model of Southern Hemisphere marsupial biogeography.
AB  - Recent molecular data strongly support the monophyly of all extant Australian and
      New Guinean marsupials (Eomarsupialia) to the exclusion of extant South American
      marsupials. This, together with available geological and fossil evidence, has
      been used to argue that the presence of marsupials in Australia is simply the
      result of a single dispersal event from South America during the latest
      Cretaceous or Palaeocene, without subsequent dispersals between the two
      continents. Here, I describe an isolated ankle bone (calcaneus) of a metatherian
      from the early Eocene Tingamarra Local Fauna in northeastern Australia.
      Strikingly, this specimen, QM F30060, lacks the 'continuous lower ankle joint
      pattern' (CLAJP), presence of which is a highly distinctive apomorphy of the
      marsupial clade Australidelphia, which includes Eomarsupialia, the living South
      American microbiotherian Dromiciops and the Tingamarran fossil marsupial
      Djarthia. Comparisons with a range of marsupials and stem-metatherians strongly
      suggest that the absence of the CLAJP in QM F30060 is plesiomorphic, and that
      this specimen represents the first unequivocal non-australidelphian
      ('ameridelphian') metatherian known from Australia. This interpretation is
      confirmed by phylogenetic analyses that place QM F30060 within (crown-group)
      Marsupialia, but outside Australidelphia. Based on these results, the
      distribution of marsupials within Gondwana cannot be explained by simply a single
      dispersal event from South America and Australia. Either there were multiple
      dispersals by marsupials (and possibly also stem-metatherians) between South
      America and Australia, in one or both directions, or, alternatively, there was a
      broadly similar metatherian fauna stretching across southern South America,
      Antarctica and Australia during the Late Cretaceous-early Palaeogene.

PMID- 22864963
TI  - Light-mimicking cockroaches indicate Tertiary origin of recent terrestrial
      luminescence.
AB  - Bioluminescence is a common feature of the communication and defence of marine
      organisms, but this phenomenon is highly restricted in the terrestrial biota.
      Here, we present a geographical distribution of only the third order of
      luminescent insects--luminescent cockroaches, with all 13 known and/or herein
      reported new living species (based on deposited specimens). We show that, for the
      first time, photo-characteristics of three examined species are nearly identical
      with those of toxic luminescent click beetles, which they mimic. These
      observations are the evidence for the mimicry by light--a new type of defensive,
      batesian and interordinal mimicry. Our analysis surprisingly reveals an
      evolutionary novelty of all living luminescent insects, while in the sea (and
      possibly in the soil) luminescence is present also phylogenetically in very
      primitive organisms.

PMID- 22864965
TI  - Assessment of an imiquimod-induced psoriatic mouse model in relation to oxidative
      stress.
AB  - Psoriasis is a chronic inflammatory skin disease that is thought to be related to
      oxidative stress. Much progress has been made in understanding the
      pathophysiology of psoriasis in relation to the immunologic and antioxidant
      systems. However, this progress has been hindered by the lack of an appropriate
      animal model for psoriasis. Recently, imiquimod (IQM)-induced psoriasis-like
      cutaneous inflammation has been reported in mice and humans. We verified the
      usefulness of an IQM-induced mouse model in relation to the antioxidant system.
      BALB/C female mice at 8-10 weeks of age were treated with IQM cream in this
      study. We analyzed clinical and histopathological changes. Increased reactive
      oxygen species production was measured by glutathione assay. Levels of
      myeloperoxidase (MPO) and superoxide dismutase-1 (SOD1) were determined by
      western blotting and immunohistochemical analyses. The activity of SOD was
      measured by a SOD activity assay kit. Application of IQM-induced skin
      inflammation similar to psoriasis in clinical and histopathological aspects.
      Accumulation of immune cells was confirmed. Oxidative stress was increased, the
      antioxidant enzyme MPO levels were increased, and both SOD levels and activity
      were decreased. In conclusion, the IQM-induced mouse model showed an aberrant
      antioxidant system. Levels of MPO and oxidative stress were increased, and the
      level and activity of SOD were decreased. Since this model seemed to be an
      appropriate model for psoriasis, it can be used to further study the pathogenic
      role of redox imbalance in psoriasis.

PMID- 22864966
TI  - Sulpiride and refractory panic disorder.

PMID- 22864968
TI  - Ecofriendly control of potato late blight causative agent and the potential role
      of lactic acid bacteria: a review.
AB  - In times of increasing societal pressure to reduce the application of pesticides
      on crops, demands for environmentally friendly replacements have intensified. In
      the case of late blight, a devastating potato plant disease, the historically
      most widely known plant destroyer has been the oomycete Phytophthora infestans.
      To date, the most important strategy for control of this pathogen has been the
      frequent application of fungicides. Due to the aforementioned necessity to move
      away from traditional chemical treatments, many studies have focused on finding
      alternative ecofriendly biocontrol systems. In general, due to the different
      modes of actions (i.e. antagonistic effects or induction of plant defence
      mechanisms), the use of microorganisms as biological control agents has a
      definite potential. Amongst them, several species of lactic acid bacteria have
      been recognised as producers of bioactive metabolites which are functional
      against a broad spectrum of undesirable microorganisms, such as fungi, oomycetes
      and other bacteria. Thus, they may represent an interesting tool for the
      development of novel concepts in pest management. This review describes the
      present situation of late blight disease and summarises current literature
      regarding the biocontrol of the phytopathogen P. infestans using antagonistic
      microorganisms.

PMID- 22864967
TI  - Differential effects of environmental enrichment, social-housing, and isolation
      rearing on a rat gambling task: dissociations between impulsive action and risky
      decision-making.
AB  - RATIONALE: Decision-making deficits, measured using the Iowa Gambling Task (IGT),
      are observed in many psychiatric populations. Additionally, evidence suggests
      that the environment also influences the development of these same disorders.
      OBJECTIVE: To determine the direct influence of the environment on decision
      making by utilizing the rat gambling task (rGT), a risky decision-making test
      modeled after the IGT. METHODS: Male rats reared in isolation, in pairs, or in an
      enriched environment were trained on the rGT as adults. During the rGT, animals
      chose from four different options. The optimal strategy on the rGT and IGT is the
      same: to favor options associated with smaller immediate rewards and less
      punishment/loss. Impulsive action is also measured during rGT performance by
      recording the number of premature responses made, similar to the five-choice
      serial reaction time task. RESULTS: Compared to pair-housed rats, isolated and
      environmentally enriched rats were slower at learning the optimal strategy.
      However, following training, only isolation-reared rats chose the disadvantageous
      options more often. Amphetamine altered decision-making on the rGT in socially
      housed animals, yet isolates were unaffected. Conversely, amphetamine increased
      premature responding similarly in all groups. This increase was attenuated by
      prior administration of a dopamine D(1) or D(2) antagonist; however, the ability
      of amphetamine to alter decision-making was not blocked by either drug.
      CONCLUSIONS: Housing environment affects animals' ability to learn and perform a
      decision-making task. Additionally, amphetamine's effect on impulsive action
      appears to be mediated by the dopaminergic system, whereas its effect on risky
      decision-making may be mediated by other neurotransmitters.

PMID- 22864970
TI  - Biochemical aspects of red koji and tofuyo prepared using Monascus fungi.
AB  - Red koji or red mold rice is prepared by growing a genus Monascus on steamed
      rice. For centuries, it has been used in Asia for the production of fermented
      foods including red rice wine and fermented tofu. Although red koji is an
      important source of various hydrolytic enzymes critical for food fermentation,
      information on the enzymatic properties in red koji has been limited. Hydrolytic
      enzymes produced by Monascus fungi may play important roles in ripening of tofuyo
      (Japanese fermented tofu) regarding the chemical and physical properties of the
      product. This review provides an introduction of red koji, its properties, and
      the application of hydrolytic enzymes, especially aspartic proteinases and
      carboxypeptidases from Monascus fungi. We also describe tofuyo and a novel
      fermented soybean protein food using a microbial action originating from red
      koji.

PMID- 22864971
TI  - Studies on the production of branched-chain alcohols in engineered Ralstonia
      eutropha.
AB  - Wild-type Ralstonia eutropha H16 produces polyhydroxybutyrate (PHB) as an
      intracellular carbon storage material during nutrient stress in the presence of
      excess carbon. In this study, the excess carbon was redirected in engineered
      strains from PHB storage to the production of isobutanol and 3-methyl-1-butanol
      (branched-chain higher alcohols). These branched-chain higher alcohols can
      directly substitute for fossil-based fuels and be employed within the current
      infrastructure. Various mutant strains of R. eutropha with isobutyraldehyde
      dehydrogenase activity, in combination with the overexpression of plasmid-borne,
      native branched-chain amino acid biosynthesis pathway genes and the
      overexpression of heterologous ketoisovalerate decarboxylase gene, were employed
      for the biosynthesis of isobutanol and 3-methyl-1-butanol. Production of these
      branched-chain alcohols was initiated during nitrogen or phosphorus limitation in
      the engineered R. eutropha. One mutant strain not only produced over 180 mg/L
      branched-chain alcohols in flask culture, but also was significantly more
      tolerant of isobutanol toxicity than wild-type R. eutropha. After the elimination
      of genes encoding three potential carbon sinks (ilvE, bkdAB, and aceE), the
      production titer improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol.
      Semicontinuous flask cultivation was utilized to minimize the toxicity caused by
      isobutanol while supplying cells with sufficient nutrients. Under this
      semicontinuous flask cultivation, the R. eutropha mutant grew and produced more
      than 14 g/L branched-chain alcohols over the duration of 50 days. These results
      demonstrate that R. eutropha carbon flux can be redirected from PHB to branched
      chain alcohols and that engineered R. eutropha can be cultivated over prolonged
      periods of time for product biosynthesis.

PMID- 22864972
TI  - Centella asiatica attenuates the neurobehavioral, neurochemical and histological
      changes in transient focal middle cerebral artery occlusion rats.
AB  - Centella asiatica has been used as psychoactive and antioxidant herbal medicine
      since ancient time. The present study was design to evaluate the preventive role
      of ethanolic extract of C. asiatica in middle cerebral artery occlusion (MCAO) in
      rats. Male Wistar rats were gavaged orally with C. asiatica extract (100, 200 and
      300 mg/kg body weight once daily) for 21 days and thereafter subjected to right
      MCAO for 2 h followed by 22-h reperfusion. Brain injury was evaluated by 2,3,5
      triphenyltetrazolium chloride and hematoxylin and eosin staining. Behavioural
      outcomes as neurological deficit, rota rod test, and grip strength were assessed.
      In addition, lipid peroxidation, enzymatic and non enzymatic antioxidants were
      analyzed to assess the oxidative stress. Our results revealed that C. asiatica
      administration greatly improved neurobehavioral activity and diminished
      infarction volume along with the restored histological morphology of brain in
      MCAO rats. Furthermore, supplementation with this extract to MCAO group has
      reduced the level of thiobarbituric acid reactive species, restored glutathione
      content and augmented the activities of antioxidant enzymes-catalase, glutathione
      peroxidase, glutathione reductase, glutathione-S-transferase and superoxide
      dismutase in a dose-dependent manner in ischemic rats. The remarkable antioxidant
      activity of C. asiatica may be attributed to its bioactive triterpenes, asiatic
      acid, asiaticoside, madecassic acid and madecosside and may be translated to
      clinical level for prevention of ischemic stroke.

PMID- 22864973
TI  - Depressive rumination and the C957T polymorphism of the DRD2 gene.
AB  - Depressed individuals who ruminate have difficulties learning from punishment and
      suppressing task-irrelevant information. The C957T polymorphism of the DRD2 gene,
      which affects functioning of D2 dopamine receptors (DRD2) that are expressed
      predominantly in the indirect pathway of the basal ganglia, has been found to
      influence suppression and punishment learning. Given these associations, we
      examined in the present study whether depressive rumination is related to the
      C957T polymorphism in 317 clinically depressed individuals and 317 never
      depressed control individuals. A 2 * 2 (diagnostic group *C957T polymorphism)
      analysis of variance conducted on depressive rumination scores yielded a
      significant interaction of group and C957T: Individuals with two 957C alleles
      reported higher levels of depressive rumination than did individuals with one or
      two 957T alleles if they were depressed, but not if they were healthy. The
      present findings suggest that the dopaminergic system and DRD2 are related to the
      frequency of maladaptive rumination in depressed individuals. Thus, DRD2 may be
      an important target for the pharmacological treatment of depressive rumination.

PMID- 22864974
TI  - Tracheal compression by the gastric tube in esophageal cancer with ankylosing
      spondylitis and an analysis of the mediastinal condition in 84 cases of
      esophagectomy: report a case.
AB  - Pneumonia, recurrent nerve injury and anastomotic leakage are common
      complications occurring after esophagectomy. However, there have so far been few
      reports on tracheal compression by the gastric tube. The patient was a 66-year
      old female with a history of ankylosing spondylitis and esophageal superficial
      squamous carcinoma treated with endoscopic mucosal resection. The new lesion was
      located just next to the last treated lesion. Therefore, it was difficult to
      treat this lesion endoscopically because of severe stenosis and scarring due to
      the previous treatment. Transhiatal esophagectomy was therefore performed.
      However, severe tracheal obstruction occurred following extubation after the
      surgery due to compression caused by the gastric tube. This case was successfully
      treated with a mediastinal pleural incision through a right thoracotomy. The
      distance between the sternum and the vertebra in this case was narrower than
      normal, thereby inducing this rare condition. 

PMID- 22864975
TI  - Intravital imaging of gastrointestinal diseases in preclinical models using two
      photon laser scanning microscopy.
AB  - Two-photon laser scanning microscopy (TPLSM), relying on two-photon excitation
      restricted to the focal plane, has become the gold standard in biomedical
      research because of its ability to produce high-resolution, higher penetrating
      imaging of biological materials over an extended duration without an significant
      photobleaching. Intravital (in vivo) imaging using TPLSM for intra-abdominal
      organs has long been a technical challenge because of the difficulty of achieving
      high-quality and higher magnification imaging with acceptable cardiac and
      respiratory motion artifacts. A method of intravital TPLSM was developed using an
      organ-stabilizing system for imaging the intra-abdominal organs of green
      fluorescent protein transgenic mice. This method was further refined for the time
      series imaging of intra-abdominal organs in the same mouse model using intravital
      TPLSM. These procedures allow the observation of not only a single cell or tissue
      microenvironment at a higher penetrating depth for a longer period of time but
      also to observe the same organ of the same mouse at multiple time points in
      preclinical models. This report presents the general principles and properties of
      TPLSM for biomedical research. In addition, the methods and the usefulness of
      time-series intravital TPLSM imaging for preclinical gastrointestinal diseases is
      discussed.

PMID- 22864976
TI  - Mathematical models of the generation of radiation-induced DNA double-strand
      breaks.
AB  - The double-strand break (dsb) is one of the most critical lesions leading to a
      variety of radiobiological effects. In this paper, we reconsider the previously
      constructed and generally accepted mathematical models for dsb generation, and
      give a concrete mathematical basis for the generation of dsbs and the calculation
      of the number of induced dsbs, under the assumption of randomness in the break
      location in DNA and in the number of breaks. Using these models based on the
      Poisson distribution and the binomial distribution, we calculate the dose
      dependence of dsb generation. We deduced from our models that the dose dependence
      of the number of dsbs is described approximately as a quadratic form in both
      distribution models where dsb generation is accounted for by two ssbs. Previously
      reported experimental data on the dsb generation in phage DNA was found to be in
      good agreement with our models. Though the widely used model, the linear
      quadratic (LQ) model or the molecular theory of dsb formation based on the
      Poisson distribution, also gives the quadratic term, in spite of rough estimates
      or some mathematical incompleteness, a marked feature of our formulation is the
      absence of a parameter like the [Formula: see text] in the quadratic term that
      requires experimental data to determine. Thus in this study we provide
      mathematical validity to the generally accepted models of the number of dsb.

PMID- 22864977
TI  - Development of a physiologically based pharmacokinetic model for the rat central
      nervous system and determination of an in vitro-in vivo scaling methodology for
      the blood-brain barrier permeability of two transporter substrates, morphine and
      oxycodone.
AB  - A whole-body physiologically based pharmacokinetic (PBPK) model was developed for
      the prediction of unbound drug concentration-time profiles in the rat brain, in
      which drug transfer across the blood-brain barrier (BBB) was treated
      mechanistically by separating the parameters governing the rate (permeability) of
      BBB transfer from brain binding. An in vitro-in vivo scaling strategy based on
      Caco-2 cell permeability was proposed to extrapolate the active transporter
      driven component of this permeability, in which a relative activity factor, RAF,
      was estimated by fitting the model to rat in vivo profiles. This scaling factor
      could be interpreted as the ratio of transporter activity between the in vitro
      system and the in vivo BBB, for a given drug in a given in vitro system. Morphine
      and oxycodone were selected to evaluate this strategy, as substrates of BBB
      located efflux and influx transporters, respectively. After estimation of their
      respective RAFs using the rat model, the PBPK model was used to simulate human
      brain concentration profiles assuming the same RAF, and the implications of this
      were discussed.

PMID- 22864978
TI  - Effects of 24-epibrassinolide on the photosynthetic characteristics, antioxidant
      system, and chloroplast ultrastructure in Cucumis sativus L. under Ca(NO(3))(2)
      stress.
AB  - The effects of 0.1 MUM 24-epibrassinolide (EBL) on plant growth (plant height,
      leaf area, fresh weight, and dry weight), chlorophyll content, photosynthetic
      characteristics, antioxidant enzymes, and chloroplast ultrastructure were
      investigated using cucumber seedlings (Cucumis sativus L. cv. Jinyou No. 4) with
      80 mM Ca(NO(3))(2) to induce stress. The presence of Ca(NO(3))(2) caused
      significant reductions in net photosynthetic rate (P(N)), stomatal conductance
      (Gs), intercellular CO(2) concentration (Ci), and transpiration rate (Tr) of
      leaves. In addition, Ca(NO(3))(2) markedly reduced the chlorophyll content and
      inhibited photochemical activity, including the actual photochemical efficiency
      (PhiPSII). In contrast, EBL increased the chlorophyll content, especially
      chlorophyll b, and minimized the harmful effects on photosynthesis caused by the
      Ca(NO(3))(2). The application of EBL to the plants subjected to Ca(NO(3))(2)
      enhanced photochemical activity. EBL protected the photosynthetic membrane system
      from oxidative damage due to up-regulating the capacity of the antioxidant
      systems. Microscopic analyses revealed that Ca(NO(3))(2) affected the structure
      of the photosynthetic apparatus and membrane system and induced damage of granal
      thylakoid layers, while EBL recovered the typical shape of chloroplasts and
      promoted the formation of grana. Taken together, EBL compensated for
      damage/losses by Ca(NO(3))(2) due to the regulation of photosynthetic
      characteristics and the antioxidant system.

PMID- 22864980
TI  - Clinical course of patients diagnosed with severe aortic stenosis in the
      Rotterdam area: insights from the AVARIJN study.
AB  - OBJECTIVE: To prospectively evaluate the clinical course of patients with severe
      aortic stenosis (AS) and identify factors associated with treatment selection and
      patient outcome. METHODS: Patients diagnosed with severe AS in the Rotterdam area
      were included between June 2006 and May 2009. Patient characteristics,
      echocardiogram, brain natriuretic peptide (NT-proBNP), and treatment strategy
      were assessed at baseline, and after 6, 12, and 24 months. Endpoints were aortic
      valve replacement (AVR) / transcatheter aortic valve implantation (TAVI) and
      death. RESULTS: The study population comprised 191 patients, 132 were symptomatic
      and 59 asymptomatic at study entry. Two-year cumulative survival of symptomatic
      patients was 89.8 % (95 % CI 79.8-95.0 %) after AVR/TAVI and 72.6 % (95 % CI 59.7
      82.0 %) with conservative treatment. Two-year cumulative survival of asymptomatic
      patients was 91.5 % (95 % CI 80.8-96.4 %). Two-year cumulative incidence of
      AVR/TAVI was 55.9 % (95 % CI 47.5-63.5 %) in symptomatic patients. Sixty-eight
      percent of asymptomatic patients developed symptoms, median time to symptoms was
      13 months; AVR/TAVI cumulative incidence was 38.3 % (95 % CI 23.1-53.3 %).
      Elderly symptomatic patients with multiple comorbidities were more likely to
      receive conservative treatment. CONCLUSIONS: In contemporary Dutch practice many
      symptomatic patients do not receive invasive treatment of severe AS. Two-thirds
      of asymptomatic patients develop symptoms within 2 years, illustrating the
      progressive nature of severe AS. Treatment optimisation may be achieved through
      careful individualised assessment in a multidisciplinary setting.

PMID- 22864979
TI  - Reversal of prenatal morphine exposure-induced memory deficit in male but not
      female rats.
AB  - Impaired memory performance in offspring is one of the long-lasting
      neurobehavioral consequences of prenatal opiate exposure. Here, we studied the
      effects of prenatal morphine exposure on inhibitory avoidance memory performance
      in male and female offspring and also investigated whether these deficits are
      reversible during the postnatal development. Pregnant Wistar rats received
      morphine sulfate through drinking water, from the first day of gestation up to
      the day 13, M1-13, or to the time of delivery, M1-21. Four- and ten-week-old
      (adolescent and adult, respectively) male and female offspring were subjected to
      behavioral assays and then analysis of proteins involved in apoptosis or in
      synaptic plasticity. Results revealed that adolescent and adult female rats
      failed in passive avoidance retention task in both M1-13 and M1-21 groups.
      Adolescent and adult male offspring were similar to control animals in M1-13
      group. However M1-21 impaired retention task in prepubertal male offspring, and
      this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2
      ratio and cleaved caspase-3 were significantly increased in both M1-13 and M1-21
      adolescent and adult female rats, but only in M1-21 adolescent male rats.
      Furthermore, prenatal morphine exposure reduced the expression of brain-derived
      neurotrophic factor precursor protein in adolescent and adult female offspring
      and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin
      dependent kinase II ratio in adolescent male and female rats. Altogether, the
      results show that prenatal morphine exposure, depending on the time or duration
      of exposure, has distinct effects on male and female rats, and postnatal
      development may reverse these deficits more likely in males.

PMID- 22864981
TI  - Interstitial cells in the primate gastrointestinal tract.
AB  - Kit immunohistochemistry and confocal reconstructions have provided detailed 3
      dimensional images of ICC networks throughout the gastrointestinal (GI) tract.
      Morphological criteria have been used to establish that different classes of ICC
      exist within the GI tract and physiological studies have shown that these classes
      have distinct physiological roles in GI motility. Structural studies have focused
      predominately on rodent models and less information is available on whether
      similar classes of ICC exist within the GI tracts of humans or non-human
      primates. Using Kit immunohistochemistry and confocal imaging, we examined the 3
      dimensional structure of ICC throughout the GI tract of cynomolgus monkeys. Whole
      or flat mounts and cryostat sections were used to examine ICC networks in the
      lower esophageal sphincter (LES), stomach, small intestine and colon. Anti
      histamine antibodies were used to distinguish ICC from mast cells in the lamina
      propria. Kit labeling identified complex networks of ICC populations throughout
      the non-human primate GI tract that have structural characteristics similar to
      that described for ICC populations in rodent models. ICC-MY formed anastomosing
      networks in the myenteric plexus region. ICC-IM were interposed between smooth
      muscle cells in the stomach and colon and were concentrated within the deep
      muscular plexus (ICC-DMP) of the intestine. ICC-SEP were found in septal regions
      of the antrum that separated circular muscle bundles. Spindle-shaped histamine(+)
      mast cells were found in the lamina propria throughout the GI tract. Since
      similar sub-populations of ICC exist within the GI tract of primates and rodents
      and the use of rodents to study the functional roles of different classes of ICC
      is warranted.

PMID- 22864982
TI  - Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport,
      reduced protease regulation and skin-barrier dysfunction.
AB  - Harlequin ichthyosis (HI) is a devastating autosomal recessive congenital skin
      disease. It has been vital to elucidate the biological importance of the protein
      ABCA12 in skin-barrier permeability, following the discovery that ABCA12 gene
      mutations can result in this rare disease. ATP-binding cassette transporter A12
      (ABCA12) is a member of the subfamily of ATP-binding cassette transporters and
      functions to transport lipid glucosylceramides (GlcCer) to the extracellular
      space through lamellar granules (LGs). GlcCer are hydrolysed into
      hydroxyceramides extracellularly and constitute a portion of the extracellular
      lamellar membrane, lipid envelope and lamellar granules. In HI skin, loss of
      function of ABCA12 due to null mutations results in impaired lipid lamellar
      membrane formation in the cornified layer, leading to defective permeability of
      the skin barrier. In addition, abnormal lamellar granule formation (distorted
      shape, reduced in number or absent) could further cause aberrant production of LG
      associated desquamation enzymes, which are likely to contribute to the impaired
      skin barrier in HI. This article reviews current opinions on the patho-mechanisms
      of ABCA12 action in HI and potential therapeutic interventions based on targeted
      molecular therapy and gene therapy strategies.

PMID- 22864983
TI  - Effects of doxorubicin cancer therapy on autophagy and the ubiquitin-proteasome
      system in long-term cultured adult rat cardiomyocytes.
AB  - The clinical use of anthracyclines in cancer therapy is limited by dose-dependent
      cardiotoxicity that involves cardiomyocyte injury and death. We have tested the
      hypothesis that anthracyclines affect protein degradation pathways in adult
      cardiomyocytes. To this aim, we assessed the effects of doxorubicin (Doxo) on
      apoptosis, autophagy and the proteasome/ubiquitin system in long-term cultured
      adult rat cardiomyocytes. Accumulation of poly-ubiquitinated proteins, increase
      of cathepsin-D-positive lysosomes and myofibrillar degradation were observed in
      Doxo-treated cardiomyocytes. Chymotrypsin-like activity of the proteasome was
      initially increased and then inhibited by Doxo over a time-course of 48 h.
      Proteasome 20S proteins were down-regulated by higher doses of Doxo. The
      expression of MURF-1, an ubiquitin-ligase specifically targeting myofibrillar
      proteins, was suppressed by Doxo at all concentrations measured. Microtubule
      associated protein 1 light chain 3B (LC3)-positive punctae and both LC3-I and -II
      proteins were induced by Doxo in a dose-dependent manner, as confirmed by using
      lentiviral expression of green fluorescence protein bound to LC3 and live
      imaging. The lysosomotropic drug chloroquine led to autophagosome accumulation,
      which increased with concomitant Doxo treatment indicating enhanced autophagic
      flux. We conclude that Doxo causes a downregulation of the protein degradation
      machinery of cardiomyocytes with a resulting accumulation of poly-ubiquitinated
      proteins and autophagosomes. Although autophagy is initially stimulated as a
      compensatory response to cytotoxic stress, it is followed by apoptosis and
      necrosis at higher doses and longer exposure times. This mechanism might
      contribute to the late cardiotoxicity of anthracyclines by accelerated aging of
      the postmitotic adult cardiomyocytes and to the susceptibility of the aging heart
      to anthracycline cancer therapy.

PMID- 22864985
TI  - Cell biology solves mysteries of reproduction.
AB  - Reproduction and fertility have been objects of keen inquiry since the dawn of
      humanity. Medieval anatomists provided the first accurate depictions of the
      female reproductive system, and early microscopists were fascinated by the
      magnified sight of sperm cells. Initial successes were achieved in the in vitro
      fertilization of frogs and the artificial insemination of dogs. Gamete and embryo
      research was in the cradle of modern cell biology, providing the first evidence
      of the multi-cellular composition of living beings and pointing out the
      importance of chromosomes for heredity. In the 20th century, reproductive
      research paved the way for the study of the cytoskeleton, cell signaling, and the
      cell cycle. In the last three decades, the advent of reproductive cell biology
      has brought us human in vitro fertilization, animal cloning, and human and animal
      embryonic stem cells. It has contributed to the development of transgenesis,
      proteomics, genomics, and epigenetics. This Special Issue represents a sample of
      the various areas of reproductive biology, with emphasis on molecular and cell
      biological aspects. Advances in spermatology, ovarian function, fertilization,
      and maternal-fetal interactions are discussed within the framework of fertility
      and diseases such as endometriosis and diabetes.

PMID- 22864984
TI  - Study of transforming growth factor alpha for the maintenance of human embryonic
      stem cells.
AB  - Human embryonic stem cells (hESCs) have great potential for regenerative medicine
      as they have self-regenerative and pluripotent properties. Feeder cells or their
      conditioned medium are required for the maintenance of hESC in the
      undifferentiated state. Feeder cells have been postulated to produce growth
      factors and extracellular molecules for maintaining hESC in culture. The present
      study has aimed at identifying these molecules. The gene expression of supportive
      feeder cells, namely human foreskin fibroblast (hFF-1) and non-supportive human
      lung fibroblast (WI-38) was analyzed by microarray and 445 genes were found to be
      differentially expressed. Gene ontology analysis showed that 20.9% and 15.5% of
      the products of these genes belonged to the extracellular region and regulation
      of transcription activity, respectively. After validation of selected
      differentially expressed genes in both human and mouse feeder cells, transforming
      growth factor alpha (TGFalpha) was chosen for functional study. The results
      demonstrated that knockdown or protein neutralization of TGFalpha in hFF-1 led to
      increased expression of early differentiation markers and lower attachment rates
      of hESC. More importantly, TGFalpha maintained pluripotent gene expression
      levels, attachment rates and pluripotency by the in vitro differentiation of H9
      under non-supportive conditions. TGFalpha treatment activated the p44/42 MAPK
      pathway but not the PI3K/Akt pathway. In addition, TGFalpha treatment increased
      the expression of pluripotent markers, NANOG and SSEA-3 but had no effects on the
      proliferation of hESCs. This study of the functional role of TGFalpha provides
      insights for the development of clinical grade hESCs for therapeutic
      applications.

PMID- 22864987
TI  - Human quercetin conjugated metabolites attenuate TNF-alpha-induced changes in
      vasomodulatory molecules in an HUASMCs/HUVECs co-culture model.
AB  - There is accumulating evidence from epidemiological and human intervention
      studies that quercetin-rich diets can protect against cardiovascular diseases.
      Quercetin glycosides are modified during metabolism, and the forms reaching the
      systemic circulation are glucuronidated, sulfated, and methylated. The aim of
      this study was to analyse the potential beneficial effects of quercetin and its
      conjugated metabolites on vascular function on a co-culture model of human
      umbilical artery smooth muscle cells and human umbilical vein endothelial cells.
      We observed that physiologically relevant metabolites of quercetin were able to
      reduce ET-1 protein and gene expression and to increase accumulation of cGMP in
      TNF-alpha-induced HUASMCs co-cultured with HUVECs. This is the first study to
      demonstrate an ability of quercetin and its conjugated metabolites, at
      physiologically achievable concentrations, to modulate vascular function in a co
      culture model comprising human vascular endothelial and smooth muscle cells.

PMID- 22864986
TI  - Assessing dementia in resource-poor regions.
AB  - The numbers and proportions of elderly are increasing rapidly in developing
      countries, where prevalence of dementia is often high. Providing cost-effective
      services for dementia sufferers and their caregivers in these resource-poor
      regions poses numerous challenges; developing resources for diagnosis must be the
      first step. Capacity building for diagnosis involves training and education of
      healthcare providers, as well as the general public, development of
      infrastructure, and resolution of economic and ethical issues. Recent progress in
      some low-to-middle-income countries (LMICs) provides evidence that partnerships
      between wealthy and resource-poor countries, and between developing countries,
      can improve diagnostic capabilities. Without the involvement of the mental health
      community of developed countries in such capacity-building programs, dementia in
      the developing world is a disaster waiting to happen.

PMID- 22864988
TI  - In vitro acanthamoebicidal activity of fusaric acid and dehydrofusaric acid from
      an endophytic fungus Fusarium sp. Tlau3.
AB  - Acanthamoeba is a genus of free-living protozoa that can cause sight- and life
      threatening diseases in man. Its control is still problematic due to the lack of
      effective and nontoxic acanthamoebicidal agents. Herein, we report the first
      finding of an in vitro killing effect of fusaric acid and dehydrofusaric acid,
      isolated from metabolites of the Fusarium fujikuroi species complex Tlau3, on
      Acanthamoeba trophozoites isolated from two clinical (AS, AR) and two soil (S3,
      S5) samples. AS, AR, and S3 were classified as members of the T4 genotype,
      whereas S5 belongs to T5. The fungal extract was found to exhibit
      acanthamoebicidal activity, and activity-guided fractionation led to the
      isolation and identification of active principles, fusaric acid and
      dehydrofusaric acid. Their effects were in concentration- and time-dependent
      manners. Fusaric acid and dehydrofusaric acid showed IC50 values against AS
      trophozoites of 0.31 and 0.34 uM, respectively. Commercial fusaric acid displayed
      the same acanthamoebicidal activity as that of the isolated fusaric acid, and
      therefore, commercial fusaric acid was used throughout this study. IC50 values of
      commercial fusaric acid against AR, S3, and S5 trophozoites were 0.33, 0.33, and
      0.66 uM, respectively. Fusaric acid calcium salt has a history of usage as a
      hypotensive agent in humans with no observed toxicity. The present study suggests
      that fusaric acid may serve as a starting point for the development towards
      therapeutic and environmental acanthamoebicides with low toxicity to humans.

PMID- 22864989
TI  - Botanical-drug interactions: a scientific perspective.
AB  - There is a continued predisposition of concurrent use of drugs and botanical
      products. A general lack of knowledge of the interaction potential together with
      an under-reporting of botanical use poses a challenge for the health care
      providers and a safety concern for patients. Botanical-drug interactions increase
      the patient risk, especially with regard to drugs with a narrow therapeutic index
      (e.g., warfarin, cyclosporine, and digoxin). Examples of case reports and
      clinical studies evaluating botanical-drug interactions of commonly used
      botanicals in the US are presented. The potential pharmacokinetic and
      pharmacodynamic bases of such interactions are discussed, as well as the
      challenges associated with the interpretation of the available data and
      prediction of botanical-drug interactions. Recent FDA experiences with botanical
      products and interactions including labeling implications as a risk management
      strategy are highlighted.

PMID- 22864990
TI  - A study on the effects of lead, cadmium and phosphorus on the lead and cadmium
      uptake efficacy of Viola baoshanensis inoculated with arbuscular mycorrhizal
      fungi.
AB  - The effect of indigenous arbuscular mycorrhizal (AM) fungi on lead (Pb) and
      cadmium (Cd) uptake by the hyperaccumulator plant Viola baoshanensis was studied
      in greenhouse pot experiments. Seedlings of V. baoshanensis inoculated without or
      with indigenous AM fungi were grown in paddy soil with the addition of Pb at 0,
      500, 1000 and 1500 mg kg(-1), or of Cd at 0, 50,100, 200 mg kg(-1), or in mine
      soil with the addition of phosphorus at 0, 50, 250, 500 mg kg(-1). AM
      colonization increased shoot biomass at low phosphorus levels, and this
      beneficial effect was diminished or reversed by high phosphorus availability. AM
      colonization decreased shoot Cd concentrations regardless of the availability of
      Cd and phosphorus, but the mechanisms involved varied with Cd availability. At
      low Cd bioavailability, reduced Cd uptake was due to decreased Cd translocation
      from the roots to the shoots, whereas that was attributed to reduced root uptake
      at high Cd bioavailability. In contrast, the effect of AM colonization on shoot
      Pb varied with the availability of phosphorous and Pb. Our results show that the
      interactions between V. baoshanensis and indigenous AM fungi were modified by the
      availability of Pb, Cd and phosphorus.

PMID- 22864991
TI  - Graphene transfer: key for applications.
AB  - The first micrometer-sized graphene flakes extracted from graphite demonstrated
      outstanding electrical, mechanical and chemical properties, but they were too
      small for practical applications. However, the recent advances in graphene
      synthesis and transfer techniques have enabled various macroscopic applications
      such as transparent electrodes for touch screens and light-emitting diodes (LEDs)
      and thin-film transistors for flexible electronics in particular. With such
      exciting potential, a great deal of effort has been put towards producing larger
      size graphene in the hopes of industrializing graphene production. Little less
      than a decade after the first discovery, graphene now can be synthesized up to 30
      inches in its diagonal size using chemical vapour deposition methods. In making
      this possible, it was not only the advances in the synthesis techniques but also
      the transfer methods that deliver graphene onto target substrates without
      significant mechanical damage. In this article, the recent advancements in
      transferring graphene to arbitrary substrates will be extensively reviewed. The
      methods are categorized into mechanical exfoliation, polymer-assisted transfer,
      continuous transfer by roll-to-roll process, and transfer-free techniques
      including direct synthesis on insulating substrates.

PMID- 22864992
TI  - Peptidoglycan fragments stimulate resuscitation of "non-culturable" mycobacteria.
AB  - Resuscitation promoting factors (Rpfs), belonging to a family of secreted
      actinobacterial proteins with predicted peptidoglycan (PG) hydrolytic activities,
      participate in the reactivation of dormant cells. In the present study we
      demonstrate that a recombinant truncated form of Micrococcus luteus Rpf
      hydrolyzes isolated PG of Mycobacterium smegmatis and Mycobacterium tuberculosis
      liberating PG fragments of different size. These fragments possess stimulatory
      activity toward "non-culturable" dormant M. smegmatis and M. tuberculosis cells,
      similar to the activity of recombinant Rpf. Relatively large PG fragments (0.1
      0.5 MUm) obtained either by Rpf digestion or by PG ultrasonication revealed
      resuscitation activities when added in concentrations 0.1-0.2 MUg/ml to the
      resuscitation medium. It is suggested that PG fragments could either directly
      activate the resuscitation pathway of dormant mycobacteria or serve as a
      substrate for endogenous Rpf, resulting in low molecular weight products with
      resuscitation activity. Whilst both suggestions are plausible, it was observed
      that PG-dependent resuscitation activity was suppressed by means of a specific
      Rpf inhibitor (4-benzoyl-2-nitrophenylthiocyanate), which provides additional
      support for the second of these possibilities.

PMID- 22864993
TI  - Evolution Born of Moisture: Analogies and Parallels Between Anaximander's Ideas
      on Origin of Life and Man and Later Pre-Darwinian and Darwinian Evolutionary
      Concepts.
AB  - This study focuses on the origin of life as presented in the thought of
      Anaximander of Miletus but also points to some parallel motifs found in much
      later conceptions of both the pre-Darwinian German romantic science and post
      Darwinian biology. According to Anaximander, life originated in the moisture
      associated with earth (mud). This moist environment hosted the first living
      creatures that later populated the dry land. In these descriptions, one can trace
      the earliest hints of the notion of environmental adaptation. The origin of
      humans was seen as connected in some way with fish: ancient humans were supposed
      to have developed inside fish-like animals. Anaximander took into account changes
      in the development of living creatures (adaptations) and speculated on the
      origins of humans. Similar ideas are found also in the writings of much later,
      eighteenth and nineteenth century authors who were close to the tradition of
      German romantic science. We do not argue that these later concepts are in any way
      directly linked with those of the pre-Socratics, but they show surprising
      parallels in, e.g., the hypothesis that life originated in a moist environment or
      the supposition that human developed from fish-like ancestors. These
      transformations are seen as a consequence of timeless logic rather than as
      evolution in historical terms. Despite the accent on the origin of living things,
      both Anaximander and the  later Naturphilosophen lack in their notions the
      element most characteristic of  Darwin's thought, that is, the emphasis on
      historicity and uniqueness of all that comes into being.

PMID- 22864994
TI  - Determining the impact of US mammography screening guidelines on patient survival
      in a predominantly African American population treated in a public hospital
      during 2008.
AB  - BACKGROUND: In November 2009, the US Preventive Service Task Force (USPSTF)
      published updated breast cancer screening guidelines. This marked a change from
      the 2002 recommendations and a significant divergence from the American Cancer
      Society (ACS) guidelines. In the current study, the potential effect of using the
      revised 2009 USPSTF guidelines on patient disease stage and survival were
      evaluated and compared with those actually observed and to predicted under ACS
      recommendations. METHODS: A retrospective chart review was performed for 84
      patients who were diagnosed with stage I through III breast cancer at Grady
      Memorial Hospital during 2008. Previously published tumor volume doubling times
      were used to model an equation that would estimate tumor sizes. For each patient,
      a disease stage at diagnosis was predicted, and outcomes were modeled as though
      the patient had been screened according to the recommended versions of the ACS
      and USPSTF guidelines. Patient survival rates were then estimated based on
      prognostic data according to disease stage. RESULTS: The average age of patients
      in the study was 55 years, and 85% were African American. The USPSTF guidelines
      predicted later stages at diagnosis (14% stage I, 73% stage II), whereas the ACS
      guidelines predicted earlier stages (47% stage I, 53% stage II). CONCLUSIONS: A
      large stage migration was predicted, indicating significantly earlier diagnosis,
      when the ACS-recommended screening guidelines were followed. The authors
      concluded that practitioners should understand how race and/or socioeconomic
      factors increase the risk of breast cancer and should be encouraged to prioritize
      discussions regarding the benefits and risks of annual mammographic screening,
      especially among women who have a potentially greater risk of developing breast
      cancer at a younger age.

PMID- 22864995
TI  - Vaccination coverage in children with juvenile idiopathic arthritis followed at a
      paediatric tertiary care centre.
AB  - OBJECTIVE: To evaluate the vaccination coverage rate of patients with JIA
      followed at a paediatric tertiary care centre and to determine the coverage rate
      for individual vaccines required as per the Quebec Immunization Protocol.
      METHODS: Consecutive JIA patients coming for their scheduled visit were included
      if they were between 2 and 18 years of age and if they had an available written
      immunization record. Descriptive statistics were used to evaluate the proportion
      of children with complete vaccination status according to the Quebec Immunization
      Protocol at 2.5, 10.5 years and at their last clinic visit. RESULTS: A total of
      200 patients were included. Complete vaccination according to schedule was
      identified in only 52% of patients at 2.5 years, 68% at 10.5 years and 61% at
      their last clinic visit. The vaccination coverage rate for individual vaccines
      was good overall with the exception of low measles, mumps and rubella vaccine
      coverage at 2.5 years (58%). CONCLUSION: Despite overall good vaccination
      coverage rate for individual vaccines, only 61% of our cohort had a complete
      vaccination status at their last clinic visit. Measures to optimize vaccination
      coverage, such as catch-up vaccination, should be implemented when possible.

PMID- 22864996
TI  - The association between parity and knee cartilage in young women.
AB  - OBJECTIVES: There have been no reported studies of the association between parity
      and cartilage in young individuals. The aim of this study was to describe the
      association between parity, cartilage volume and cartilage defects in women aged
      31-41 years. METHODS: Cross-sectional study of 144 women, mean age 36 years and
      BMI 25 kg/m(2), who were participants in an established prospective study. Parity
      was assessed using a questionnaire. Knee (medial tibial, lateral tibial and
      patellar) cartilage volume, cartilage defects (grade 0-4 depending on the
      severity of cartilage thickness loss at tibial and patellar sites) and tibial
      bone area were assessed using T1-weighted fat-suppressed MRI. RESULTS: The
      prevalence of cartilage defects (grade >=2) in this population was 13%. Parity
      was associated with a higher risk of cartilage defects at the patellar
      [prevalence ratio (PR) per birth 1.52, 95% CI 1.05, 2.21; PR parous vs
      nulliparous 1.93, 95% CI 0.66, 5.65], but not tibial sites, after adjustment for
      confounders including age, BMI, smoking, physical activity, knee injury and
      tibial bone area. This association between parity and patellar cartilage defects
      was stronger for those women who had three or more births (vs nulliparous, PR
      5.27, 95% CI 1.39, 20.01). There were no significant associations between parity
      and cartilage volume. CONCLUSION: Parity was associated with knee cartilage
      defects primarily at the patellar site in this sample of young women. This
      association was more apparent with increasing number of live births, suggesting a
      possible adverse effect of parity on knee cartilage.

PMID- 22864997
TI  - Pulmonary function as a cause of cognitive aging.
AB  - Human aging is associated with decline in cognitive and physical functioning.
      Although pulmonary function predicts long-term performance (up to 10 years) on
      measures of cognitive function, recent data suggest the opposite relationship:
      Cognitive decline predicts self-reported physical limitations. In the study
      reported here, we utilized dual-change-score models to determine the directional
      relationship between pulmonary and cognitive function. Our sample consisted of
      832 participants (ages 50-85 years at baseline), who were assessed in up to seven
      waves of testing across 19 years as part of the longitudinal Swedish
      Adoption/Twin Study of Aging. Changes in pulmonary function led to subsequent
      changes in fluid cognitive function, specifically, in tasks reflecting
      psychomotor speed and spatial abilities. There was no evidence that declines in
      cognitive function led to subsequent declines in pulmonary function. Thus, these
      data indicate a directional relationship from decreased pulmonary function to
      decreased cognitive function, a finding that underscores the importance of
      maintaining pulmonary function to ensure cognitive performance.

PMID- 22864998
TI  - Improved intestinal absorption of a poorly water-soluble oral drug using mannitol
      microparticles containing a nanosolid drug dispersion.
AB  - A nozzle for a spray dryer that can prepare microparticles of water-soluble
      carriers containing various nanoparticles in a single step was previously
      developed in our laboratory. To enhance the solubility and intestinal absorption
      of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble
      drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and
      EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone
      methanol and aqueous MAN solutions were simultaneously supplied through different
      liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion
      was nanoprecipitated in the MAN solution using an antisolvent mechanism and
      rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was
      amorphous and had higher physical stability according to powder X-ray diffraction
      and differential scanning calorimetry analysis. The bioavailability of PBL in PBL
      EUD S-100-MAN microparticles after oral administration in rats was markedly
      higher (14- and 6.2-fold, respectively) than that of the original PBL powder and
      PBL-MAN microparticles. These results demonstrate that the composite
      microparticles containing a nanosized solid dispersion of a poorly water-soluble
      drug prepared using the spray nozzle developed by us should be useful to increase
      the solubility and bioavailability of drugs after oral administration.

PMID- 22864999
TI  - Inhibitory effects of panduratin A on allergy-related mediator production in rat
      basophilic leukemia mast cells.
AB  - Immediate-type hypersensitivity is characterized by elevated levels of
      immunoglobulin E (IgE) and activated mast cell plays a crucial role by releasing
      granule contents, lipid-derived mediators, cytokines, and chemokines. To evaluate
      the antiallergic effects of panduratin A isolated from Boesenbergia pandurata
      Roxb., we determined its effects on calcium (Ca(2+)) influx, degranulation, and
      inflammatory mediators in calcium ionophore A23187 and phorbol 12-myristate 13
      acetate (PMA)-stimulated rat basophilic leukemia (RBL-2H3) cells. Panduratin A
      (20 MUM) inhibited secretion of beta-hexosaminidase (46.69 +/- 9.6 %), histamine
      (34.32 +/- 2.1 %), and Ca(2+) influx (43.84 %). Panduratin A reduced the
      production of prostaglandin E(2) (PGE(2), 47.58 +/- 3.4 %), leukotriene B(4)
      (LTB(4), 98.15 +/- 1.6 %), and the mRNA expression of cyclooxygenase-2, 5
      lipoxygenase, interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha.
      Furthermore, panduarin A attenuated phosphorylation of Akt, the mitogen-activated
      protein kinases (MAPK) extracellular signal-regulated kinase (ERK), p38, and c
      Jun N-terminal kinase (JNK) expression. These results indicate that panduratin A
      might be useful as an agent against immediate-type hypersensitivity.

PMID- 22865001
TI  - Medium optimization and proteome analysis of (R,R)-2,3-butanediol production by
      Paenibacillus polymyxa ATCC 12321.
AB  - Paenibacillus polymyxa can produce the (R,R)-stereoisomer of 2,3-butanediol (2,3
      BDL) which is industrially very useful. Two important factors affecting (R,R)-BDL
      production by P. polymyxa ATCC 12321, medium composition, and addition of acetic
      acid to the culture were investigated in this study with accompanying comparative
      proteomic analysis. For this purpose, a simple control strategy of O(2) supply
      was applied on the basis of an optimized basal medium: after a short period of
      batch cultivation with relatively high O(2) supply, the culture is switched into
      strong O(2) limitation, thereby promoting BDL formation. Three parallel fed-batch
      cultures starting from the same batch culture in an early stationary phase were
      then comparatively studied: the first one was running as control with the only
      change of O(2) supply; the second was, in addition, supplemented with 0.5 g/L
      yeast extract; and the third one was further added with 6 g/L acetate. Proteomic
      analyses of the three fed-batch cultures identified more than 86 proteins
      involved primarily in the central carbon metabolism, amino acid biosynthesis,
      energy metabolism, and stress responses. The examination of expression patterns
      of selected proteins, especially combined with fermentation data, gave valuable
      insights into the metabolic regulation of P. polymyxa under the different given
      conditions. Based on the proteomic analysis and further medium optimization
      studies, methionine was identified as one major growth-limiting factor in the
      basal medium and explains well the effect of yeast extract. Acetic acid was found
      to trigger the so far less studied acetone biosynthesis pathway in this organism.
      The latter is suggested in turn to enhance the switch from acidogenesis to
      solventogenesis. Thus, these findings extended our knowledge about BDL formation
      in P. polymyxa and provided useful information for further strain and process
      optimization.

PMID- 22865000
TI  - Pathological and behavioral risk factors for higher serum C-reactive protein
      concentrations in free-living adults--a Brazilian community-based study.
AB  - Low-grade chronic systemic inflammation is often associated with chronic non
      communicable diseases, and its most frequently used marker, the C-reactive
      protein (CRP), has become an identifier of such diseases as well as an
      independent predictor for cardiovascular disorders and mortality. CRP is produced
      in response to pro-inflammatory signaling and to individual and behavioral
      factors, leading to pathological states. The aim of this study was to rank the
      predicting factors of high CRP concentrations in free-living adults from a
      community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for
      anthropometric characteristics, dietary intake, clinical and physical tests, and
      blood analysis. Subjects were assigned to groups, according to CRP
      concentrations, as normal CRP (G1; <3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0
      mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical
      comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and
      prediction of altered values in increasing CRP was evaluated by proportional
      hazard models (odds ratio). CRP distribution was influenced by gender, body mass
      index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The
      higher CRP group was discriminated by the above variables in addition to lower
      VO(2max), serum metabolic syndrome components (triglycerides, glucose, and HDL
      cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric
      acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood
      leukocytes, and hyperglycemia remained as independent predictors for increased
      serum CRP concentrations. Intervention procedures to treat low-grade chronic
      inflammation in overweight women would mainly focus on restoring muscle mass and
      functions in addition to an antioxidant-rich diet.

PMID- 22865002
TI  - Sealing of transected neurites of rat B104 cells requires a diacylglycerol PKC
      dependent pathway and a PKA-dependent pathway.
AB  - To survive, neurons and other eukaryotic cells must rapidly repair (seal)
      plasmalemmal damage. Such repair occurs by an accumulation of intracellular
      vesicles at or near the plasmalemmal disruption. Diacylglycerol (DAG)-dependent
      and cAMP-dependent proteins are involved in many vesicle trafficking pathways.
      Although recent studies have implicated the signaling molecule cAMP in sealing,
      no study has investigated how DAG and DAG-dependent proteins affect sealing. By
      means of dye exclusion to assess Ca(2+)-dependent vesicle-mediated sealing of
      transected neurites of individually identifiable rat hippocampal B104 cells, we
      now report that, compared to non-treated controls, sealing probabilities and
      rates are increased by DAG and cAMP analogs that activate PKC and Munc13-1 and
      PKA. Sealing is decreased by inhibiting DAG-activated novel protein kinase C
      isozymes eta (nPKCeta) and theta (nPKCtheta) and Munc13-1, the PKC effector
      myristoylated alanine rich PKC substrate (MARCKS) or phospholipase C (PLC). DAG
      increased sealing is prevented by inhibiting MARCKS or protein kinase A (PKA).
      Sealing probability is further decreased by simultaneously inhibiting nPKCeta,
      nPKCtheta, and PKA. Extracellular Ca(2+), DAG, or cAMP analogs do not affect this
      decrease in sealing. These and other data suggest that DAG increases sealing
      through MARCKS and that nPKCeta, nPKCtheta, and PKA are all required to seal
      plasmalemmal damage in B104 and likely all eukaryotic cells.

PMID- 22865003
TI  - Clinicopathological features and molecular analysis of primary glioblastomas in
      Moroccan patients.
AB  - Glioblastoma is the most frequent and most aggressive primary brain tumor.
      Primary and secondary glioblastomas develop through different genetic pathways.
      The aim of this study was to determinate the genetic and clinical features of
      primary glioblastoma in Moroccan patients. The blood and tumor samples were
      obtained from a group of 34 Moroccan patients affected with primary glioblastoma.
      The tumors were investigated for TP53, IDH1, and IDH2 mutations using PCR
      sequencing analysis. Clinicopathological data showed that the mean age at
      diagnosis of patients was 50.06 years, the sex ratio was 11 F/23 M, and the
      median of Karnofsky performance score was 60. About 18 % of patients were
      initially treated by total tumor resection, 41 % by subtotal, and 38 % by partial
      resection, but biopsy was performed for a single patient (3 %). Twenty-five
      patients (74 %) received radiotherapy. In addition, the median survival of the
      all patients was 13 months following diagnosis. There was a significant impact of
      higher Karnofsky performance score (KPS) (>=80) on overall survival, p-log-rank
      test = 0.0002, whereas other parameters did not show any significant differences.
      The molecular analysis revealed TP53 mutations in 3/34 (8.82 %) cases; R273H,
      R306X, and Q136X. However, none of the analyzed samples contained the R132-IDH1
      or R172-IDH2 mutations. These results showed the absence of IDH1 mutation in
      primary glioblastoma, confirming that this mutation is a hallmark of secondary
      glioblastoma. It can be used to distinguish primary from secondary glioblastomas.
      We found also that higher KPS was a significantly favorable factor in patients
      with primary glioblastoma.

PMID- 22865004
TI  - Exploring the validity of the continuum of resistance model for discriminating
      early from late and non-uptake of colorectal cancer screening: implications for
      the design of invitation and reminder letters.
AB  - BACKGROUND: The continuum of resistance model contends that respondents lie at
      one end of a continuum and non-respondents at the other with respect to factors
      demonstrated to impact on screening participation. PURPOSE: The aim of this study
      was to explore the validity of this model for the prediction of participation in
      colorectal cancer screening. METHOD: People aged 50 to 74 years were asked to
      complete a survey (n = 1,250). Eligible respondents (n = 376, 30 %) were invited
      to complete a faecal occult blood test (FOBT). The cutoff period for the
      determination of participation rates was 12 weeks, with a reminder sent at 6
      weeks. RESULTS: FOBTs were returned by n = 196 people (132 within 6 weeks, 64
      following a reminder). Participation was generally influenced by the same
      variables in both the first 6 weeks and the second 6 weeks, consistent with the
      continuum of resistance model. These variables were having known someone with
      bowel cancer and the social cognitive factor, perceptions of barriers to
      screening. There is a suggestion, however, that other factors may be
      differentially associated with early, late and non-participants. CONCLUSION:
      Participation in screening appears somewhat consistent with the continuum of
      resistance model in that early and late participants respond to some of the same
      factors. This suggests that the same messages are relevant to early, late and non
      screeners, but further consideration of what other factors may be influencing
      discrete stages of readiness to participate is necessary.

PMID- 22865005
TI  - Behavioral responses of native prey to disparate predators: naivete and predator
      recognition.
AB  - It is widely accepted that predator recognition and avoidance are important
      behaviors in allowing prey to mitigate the impacts of their predators. However,
      while prey species generally develop anti-predator behaviors through coevolution
      with predators, they sometimes show accelerated adoption of these behaviors under
      strong selection pressure from novel species. We used a field manipulation
      experiment to gauge the ability of the common ringtail possum (Pseudocheirus
      peregrinus), a semi-arboreal Australian marsupial, to recognize and respond to
      olfactory cues of different predator archetypes. We predicted that ringtails
      would display stronger anti-predator behaviors to cues of the invasive European
      red fox (Vulpes vulpes) in areas where fox impacts had been greatest, and to cues
      of the native lace monitor (Varanus varius) in areas of sympatry compared with
      allopatry. We found that ringtails fled quickly and were more alert when exposed
      to the fecal odors of both predators compared to neutral and pungent control
      odors, confirming that predator odors are recognized and avoided. However, these
      aversive responses were similar irrespective of predator presence or level of
      impact. These results suggest that selection pressure from the fox has been
      sufficient for ringtails to develop anti-predator behaviors over the few
      generations since foxes have become established. In contrast, we speculate that
      aversive responses by ringtails to the lace monitor in areas where this predator
      is absent reflect recent coexistence of the two species. We conclude that rapid
      evolution of anti-predator behaviors may occur when selection is strong. The
      maintenance of these behaviors should allow re-establishment of predator-prey
      relationships if the interactants regain sympatry via range shifts or management
      actions to reintroduce them to their former ranges.

PMID- 22865006
TI  - Detection of plutonium isotopes at lowest quantities using in-source resonance
      ionization mass spectrometry.
AB  - The in-source resonance ionization mass spectrometry technique was applied for
      quantification of ultratrace amounts of plutonium isotopes as a proof of
      principle study. In addition to an overall detection limit of 10(4) to 10(5)
      atoms, this method enables the unambiguous identification and individual
      quantification of the plutonium isotopes (238)Pu and (241)Pu which are of
      relevance for dating of radiogenic samples. Due to the element-selective
      ionization process, these isotopes can be measured even under a high surplus of
      isobaric contaminations from (238)U or (241)Am, which considerably simplifies
      chemical preparation. The technique was developed, tested, and characterized on a
      variety of synthetic and calibration samples and is presently applied to analyze
      environmental samples.

PMID- 22865007
TI  - Capillary electrophoresis ribosomal RNA single-stranded conformation
      polymorphism: a new approach for characterization of low-diversity microbial
      communities.
AB  - Capillary electrophoresis (CE) has been the principle system for nucleic acid
      analysis since the early 1990s due to its inherent advantages such as fast
      analysis time, high resolution and efficiency, minimal sample requirement, high
      detection sensitivity, and automation. In the past few decades, microbial
      community fingerprinting methods such as terminal restriction fragment length
      polymorphism and single-stranded conformation polymorphism (SSCP) have migrated
      to CE to utilize its advantages over conventional slab gel electrophoresis.
      Recently, a gel-based direct rRNA fingerprint method was demonstrated. Different
      from other existing microbial community characterization approaches, this novel
      approach is polymerase chain reaction free and capable of providing information
      on the relative abundance of rRNA from individual phylotypes in low-diversity
      samples. As a gel-based method, it has a long analysis time and relatively large
      reagent and sample requirements. Here, we addressed these limitations by
      transferring the RNA fingerprint approach to the CE platform. Analysis time
      significantly improved from 24 h to 60 min, and the use of a fluorescently
      labeled hybridization probe as the detection strategy decreased the sample
      requirement by ten-fold. The combination of fast analysis time, low sample
      requirement, and sensitive fluorescence detection makes CE-RNA-SSCP an appealing
      new approach for characterizing low-diversity microbial communities.

PMID- 22865008
TI  - Simultaneous determination and validated quantification of human insulin and its
      synthetic analogues in human blood serum by immunoaffinity purification and
      liquid chromatography-mass spectrometry.
AB  - Possible fatal complications of human insulin and its synthetic analogues like
      hypoglycemia require precise classification and quantitative determination of
      these drugs both for clinical purposes as well as for forensic toxicologists. A
      procedure was developed for the identification and quantification of human
      insulin and different long-acting as well as short-acting synthetic insulins in
      human blood serum specimens. After an immunoaffinity purification step and
      separation by liquid chromatography, the insulins were characterized by their
      five- or sixfold protonated molecule ions and diagnostic product ions. Clinical
      samples of 207 diabetic and 50 non-diabetic patients after the administration of
      human insulin or oral antidiabetics and forensic samples were analyzed for
      human/synthetic insulin concentrations. The method was validated according to
      international guidelines. Limits of detection of the insulins ranged between 1.3
      and 2.8 MUU/ml. Recoveries ranged between 33.2 % and 51.7 %. Precision data was
      in accordance with international guidelines. Clinical samples showed
      concentrations of human insulin lower than 301 MUU/ml. Our liquid chromatography
      tandem mass spectrometry procedure allows unambiguous identification and
      quantification of the intact human insulin and its intact synthetic analogues
      Humalog(r), Novolog(r), Apidra(r), Lantus(r), and Levemir(r) in human blood serum
      in clinical and overdose cases. The assay could be successfully tested in
      patients with diabetes mellitus on therapy with insulins or oral antidiabetics.

PMID- 22865009
TI  - Distribution measurements of 3,4-methylenedioxymethamphetamine and its
      metabolites in organs by matrix-assisted laser desorption/ionization imaging mass
      spectrometry using an automatic matrix spraying system with an air brush and a
      turntable.
AB  - Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI/IMS)
      is a useful tool for measuring drug distributions. To obtain reproducible
      analytical results with MALDI/IMS, it is essential to apply a homogeneous matrix
      coating onto sample surfaces. A simple and inexpensive automatic matrix spraying
      system (AMSS) with good reproducibility was developed in this study. In addition,
      drug distributions in organs were measured by MALDI/IMS using the AMSS for
      forensic toxicology applications. The AMSS was constructed from simple
      components, including an air brush, a turntable, and a microscope. Organ slices
      placed onto conductive sheets were attached to the turntable. The trigger of the
      air brush was held with a clamp to ensure that it sprayed continuously onto a
      defined area of the table. Periodic spraying of the matrix solution and
      evaporation of solvent were performed by rotating the turntable. The droplets and
      crystals on the sample surfaces were observed under a microscope attached to the
      turntable. The droplet size, rotation rate of the turntable, and the formulation
      of the matrix solution were optimized. The homogeneity of the matrix coating was
      evaluated using the coefficients of variation (CV) obtained by quantifying the
      color density of the sheet surface. The AMSS enabled more homogeneous matrix
      coating (intersheet CV = 5.4 %) than manual spraying (intersheet CV = 16.7 %)
      when 10 mL of 0.5 % aqueous trifluoroacetic acid/acetonitrile (1:3, v/v)
      containing 10 mg/mL alpha-cyano-4-hydroxycinnamic acid were sprayed as droplets
      less than 50 MUm in diameter onto a turntable rotating at 30 rpm. The
      distributions of 3,4-methylenedioxymethamphetamine (MDMA) and its main
      metabolites in the brain, liver, and kidney of a mouse that died from an MDMA
      overdose (58 mg/kg i.p.) were visualized by MALDI/IMS using the AMSS. The ion
      intensities of MDMA obtained from the same regions on three sequential kidney
      slices showed acceptable variations (CV = 2.9-8.8 % for five different regions),
      implying repeatable measurements with MALDI/IMS using the AMSS. It was revealed
      that MDMA was particularly concentrated around the brain stem and the major calix
      of the kidney. The AMSS would be suitable for preparing samples for measuring the
      distributions of drugs in organs at toxic dose levels in forensic toxicological
      applications.

PMID- 22865010
TI  - Determination of imatinib and its active metabolite N-desmethyl imatinib in human
      plasma by liquid chromatography/tandem mass spectrometry.
AB  - Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The
      pharmacokinetics of imatinib in patients with CML are characterised by large
      interpatient variability. Concentration monitoring of imatinib and its active
      metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe
      and effective use of imatinib. A rapid, simple and sensitive liquid
      chromatography/tandem mass spectrometry assay was developed for the simultaneous
      determination of imatinib and its metabolite DMI in human plasma. After proteins
      were precipitated with acetonitrile, imatinib, DMI and the internal standard D8
      imatinib were resolved on a Gemini-NX 3 MUm C18 column using gradient elution of
      0.05 % formic acid and methanol. The three compounds were detected using
      electrospray ionisation in the positive mode. Standard curves of imatinib and DMI
      were adequately fitted by quadratic equations (r > 0.999) over the concentration
      range of 10 to 2,000 ng/mL which encompasses clinical concentrations. Bias was
      <=+/-8.3 %, intra- and inter-day coefficients of variation (imprecision) were
      <=8.0 % and the limit of quantification was 10 ng/mL for both imatinib and DMI.
      The assay is being used successfully in clinical practice to enhance the safe and
      effective use of imatinib.

PMID- 22865011
TI  - The ExoMars Raman spectrometer and the identification of biogeological
      spectroscopic signatures using a flight-like prototype.
AB  - The molecular specificity of Raman spectroscopy provides a powerful tool for the
      analytical interrogation of mineralogical and many biological specimens. The
      Raman Laser Spectrometer (RLS) is a compact Raman spectrometer under development
      for deployment on the Martian surface as part of the forthcoming ESA ExoMars
      mission. This will be the first Raman instrument deployed in space. The
      scientific interpretation of the data emerging from such an instrument not only
      addresses the geological and mineral composition of the specimens but also
      enables an assessment to be made of organic biomaterials that may be preserved in
      the planetary geological record. The latter evidence centres on the residual and
      distinctive chemistry relating to the biological adaptation of the geological
      matrix that has occurred as a result of extremophilic organisms colonizing
      suitable geological niches for their survival in environmentally stressed
      habitats on Mars. These biogeological modifications have been studied
      terrestrially for Mars analogue sites and consist of both a geological component
      and residual key organic biomarkers, the recognition of which would be a prime
      factor in life detection surveys of a planetary surface and subsurface. In this
      paper, the protocols required for the Raman spectral discrimination of key
      biogeological features that may be detectable on the Martian planetary surface or
      subsurface are developed using the UK breadboard (UKBB) instrument. This
      instrument has been constructed to be functionally equivalent to the RLS flight
      instrument design in order to evaluate the feasible science return of the
      instrument which will finally be delivered to Mars. Initial Raman measurements
      using the UKBB are presented and compared with the performance of a commercial
      laboratory Raman microscope. The initial measurements reported here demonstrate
      this flight-like prototype achieves straightforward detection of biological
      signatures contained in geological matrices with Raman band signal to noise
      ratios high enough to determine sample composition by inspection and without the
      need for deconvolution or further processing.

PMID- 22865012
TI  - Trial using pig cells with the H-D antigen knocked down.
AB  - PURPOSE: This report describes an attempt to reduce the expression level of
      Hanganutziu-Deicher (H-D) antigens by small interfering RNA (siRNA) for pig
      cytidine monophospho-N-acetylneuraminic acid hydroxylase (pCMAH). METHODS: A pig
      endothelial cell (PEC) line, and PEC and fibroblasts from an
      alpha1,3galactosyltransferase knockout (GalT-KO) piglet were used. Real-time PCR
      was used to evaluate the degradation of mRNA by siRNA. The H-D antigen was
      stained, and then the cells were incubated with human serum for the FACS
      analysis. The extent of lysis in human serum was next calculated using an LDH
      assay. RESULTS: Suppression of the mRNA of pCMAH by each siRNA was first
      determined. The mixture of siRNAs for pCMAH reduced the expressions of the H-D
      antigen on the PEC and fibroblasts to a considerable extent. The further
      reduction in the xenoantigenicity for human serum of the GalT-KO cells was then
      confirmed. In addition, the PEC line showed a significant downregulation in
      complement-dependent cytotoxicity by the siRNAs, thus indicating that the anti-H
      D antigen in human serum is capable of causing lysis of the pig cells.
      CONCLUSION: pCMAH silencing by siRNA reduced the expression of the H-D antigen
      and its antigenicity, thus confirming that the H-D antigen is one of the major
      non-Gal antigens in this situation.

PMID- 22865013
TI  - Simple pyloroplasty using a linear stapler in surgery for esophageal cancer.
AB  - This article describes a simple pyloroplasty procedure using a linear stapler in
      surgery for esophageal cancer. Simple pyloroplasty was carried out using a linear
      stapler in a total of 22 patients, whose stomachs were used as esophageal
      substitutes in the surgery for esophageal cancer. Endoscopy was performed and the
      pyloric diameter was measured perioperatively. A barium meal study was conducted
      1 month after the surgery. Stapling enlarged the diameter of the pylorus by
      nearly 10 %. Endoscopy revealed a smooth inner surface of the pylorus,
      enlargement of pyloric channel, and fewer spasms of the pylorus at the 1-month
      follow-up. Postoperative barium meal studies showed good patency of all of the
      patients' gastric outlets. Simple pyloroplasty is a time-saving and non-soiling
      technique used to perform the drainage of the gastric conduit for resection of
      esophageal cancer.

PMID- 22865014
TI  - Significant improvement of chronic pain by Pregabalin after thoracotomy: report
      of four cases.
AB  - Unfortunately, many patients may have persistent pain lasting for many months, or
      even years, following thoracic surgery. No effective treatment has so far been
      established for chronic pain after thoracotomy. There are no reports of treatment
      involving Pregabalin for pain after thoracic surgery. This study reports four
      cases that showed significant improvement with Pregabalin in late-onset (notified
      during an office visit after discharge) nocturnal insomnia and in stress-induced
      ulcers caused by intercostal neuralgia after thoracotomy. 

PMID- 22865015
TI  - The composition of intern work while on call.
AB  - BACKGROUND: The work of house staff is being increasingly scrutinized as duty
      hours continue to be restricted. OBJECTIVE: To describe the distribution of work
      performed by internal medicine interns while on call. DESIGN: Prospective time
      motion study on general internal medicine wards at a VA hospital affiliated with
      a tertiary care medical center and internal medicine residency program.
      PARTICIPANTS: Internal medicine interns. MAIN MEASURES: Trained observers
      followed interns during a "call" day. The observers continuously recorded the
      tasks performed by interns, using customized task analysis software. We measured
      the amount of time spent on each task. We calculated means and standard
      deviations for the amount of time spent on six categories of tasks: clinical
      computer work (e.g., writing orders and notes), non-patient communication, direct
      patient care (work done at the bedside), downtime, transit and teaching/learning.
      We also calculated means and standard deviations for time spent on specific tasks
      within each category. We compared the amount of time spent on the top three
      categories using analysis of variance. KEY RESULTS: The largest proportion of
      intern time was spent in clinical computer work (40 %). Thirty percent of time
      was spent on non-patient communication. Only 12 % of intern time was spent at the
      bedside. Downtime activities, transit and teaching/learning accounted for 11 %, 5
      % and 2 % of intern time, respectively. CONCLUSION: Our results suggest that
      during on call periods, relatively small amounts of time are spent on direct
      patient care and teaching/learning activities. As intern duty hours continue to
      decrease, attention should be directed towards preserving time with patients and
      increasing time in education.

PMID- 22865016
TI  - Racial differences in the effect of a telephone-delivered hypertension disease
      management program.
AB  - BACKGROUND: African Americans are significantly more likely than whites to have
      uncontrolled hypertension, contributing to significant disparities in
      cardiovascular disease and events. OBJECTIVE: The goal of this study was to
      examine whether there were differences in change in blood pressure (BP) for
      African American and non-Hispanic white patients in response to a medication
      management and tailored nurse-delivered telephone behavioral program.
      PARTICIPANTS: Five hundred and seventy-three patients (284 African American and
      289 non-Hispanic white) primary care patients who participated in the
      Hypertension Intervention Nurse Telemedicine Study (HINTS) clinical trial.
      INTERVENTIONS: Study arms included: 1) nurse-administered, physician-directed
      medication management intervention, utilizing a validated clinical decision
      support system; 2) nurse-administered, behavioral management intervention; 3)
      combined behavioral management and medication management intervention; and 4)
      usual care. All interventions were activated based on poorly controlled home BP
      values. MAIN MEASURES: Post-hoc analysis of change in systolic and diastolic
      blood pressure. General linear models (PROC MIXED in SAS, version 9.2) were used
      to estimate predicted means at 6-month, 12-month, and 18-month time points, by
      intervention arm and race subgroups (separate models for systolic and diastolic
      blood pressure). KEY RESULTS: Improvement in mean systolic blood pressure post
      baseline was greater for African American patients in the combined intervention,
      compared to African American patients in usual care, at 12 months (6.6 mmHg; 95 %
      CI: -12.5, -0.7; p=0.03) and at 18 months (9.7 mmHg; -16.0, -3.4; p=0.003). At 18
      months, mean diastolic BP was 4.8 mmHg lower (95 % CI: -8.5, -1.0; p=0.01) among
      African American patients in the combined intervention arm, compared to African
      American patients in usual care. There were no analogous differences for non
      Hispanic white patients. CONCLUSIONS: The combination of home BP monitoring,
      remote medication management, and telephone tailored behavioral self-management
      appears to be particularly effective for improving BP among African Americans.
      The effect was not seen among non-Hispanic white patients.

PMID- 22865017
TI  - RESPECT-PTSD: re-engineering systems for the primary care treatment of PTSD, a
      randomized controlled trial.
AB  - BACKGROUND: Although collaborative care is effective for treating depression and
      other mental disorders in primary care, there have been no randomized trials of
      collaborative care specifically for patients with Posttraumatic stress disorder
      (PTSD). OBJECTIVE: To compare a collaborative approach, the Three Component Model
      (3CM), with usual care for treating PTSD in primary care. DESIGN: The study was a
      two-arm, parallel randomized clinical trial. PTSD patients were recruited from
      five primary care clinics at four Veterans Affairs healthcare facilities and
      randomized to receive usual care or usual care plus 3CM. Blinded assessors
      collected data at baseline and 3-month and 6-month follow-up. PARTICIPANTS:
      Participants were 195 Veterans. Their average age was 45 years, 91% were male,
      58% were white, 40% served in Iraq or Afghanistan, and 42% served in Vietnam.
      INTERVENTION: All participants received usual care. Participants assigned to 3CM
      also received telephone care management. Care managers received supervision from
      a psychiatrist. MAIN MEASURES: PTSD symptom severity was the primary outcome.
      Depression, functioning, perceived quality of care, utilization, and costs were
      secondary outcomes. KEY RESULTS: There were no differences between 3CM and usual
      care in symptoms or functioning. Participants assigned to 3CM were more likely to
      have a mental health visit, fill an antidepressant prescription, and have
      adequate antidepressant refills. 3CM participants also had more mental health
      visits and higher outpatient pharmacy costs. CONCLUSIONS: Results suggest the
      need for careful examination of the way that collaborative care models are
      implemented for treating PTSD, and for additional supports to encourage primary
      care providers to manage PTSD.

PMID- 22865018
TI  - Implementation of an electronic health record-based care management system to
      improve tobacco treatment.
AB  - BACKGROUND: Tobacco treatment is underused in primary care. We designed a Tobacco
      Care Management system to increase the delivery of treatment and reduce the
      burden on primary care providers (PCPs). A one-click functionality added to the
      electronic health record (EHR) allowed PCPs to refer smokers to a centralized
      tobacco treatment coordinator (TTC) who called smokers, provided brief
      counseling, connected them to ongoing treatment and gave feedback to PCPs.
      OBJECTIVE: To study the system's feasibility and acceptability among PCPs, and
      its utilization by smokers. DESIGN: Using a mixed methods design, we documented
      system utilization quantitatively from February 1, 2010 to July 31, 2011, and
      conducted two focus groups with PCPs in June 2011. PARTICIPANTS: Thirty-six PCPs
      and 2,894 smokers from two community health centers in Massachusetts. MAIN
      MEASURES: Quantitative: One-click referral utilization by PCPs, proportion of
      smokers referred and connected to treatment. Qualitative: PCPs' reasons for use,
      barriers to use, and experiences with feedback. KEY RESULTS: Twenty-nine PCPs (81
      %) used the functionality more than once, generating 466 referrals for 15 % of
      known smokers seen during the study. The TTC reached 260 (56 %) of the referrals
      and connected 135 (29 %) to additional treatment. The director of one center sent
      PCPs monthly feedback about their utilization compared to peers. These PCPs
      referred a greater proportion of their known smokers (18 % vs. 9 %, p<0.0001) and
      reported that monthly feedback motivated referrals. PCPs attending focus groups
      (n=24) appreciated the system's simplicity, access to updated resources, and time
      efficient way to address smoking, and wanted more feedback about cessation
      outcomes. They collectively supported the system's continuation. CONCLUSIONS: A
      novel EHR-based Tobacco Care Management system was adopted by PCPs, especially
      those receiving performance feedback, and connected one-third of referred smokers
      to treatment. The model has the potential to improve the delivery and outcomes of
      evidence-based tobacco treatment in primary care.

PMID- 22865019
TI  - [Dear subscribers].

PMID- 22865021
TI  - [Group programs of work related medical rehabilitation, MBOR, and vocational
      rehabilitation--7th Expert Meeting of the Center of Patient Education, May 10-11,
      2012 in Wuerzburg].

PMID- 22865022
TI  - The interrelationships among acculturation, social support, and postpartum
      depression symptoms among marriage-based immigrant women in Taiwan: a cohort
      study.
AB  - This cohort study assessed the structural relationships among social support,
      acculturation, and postpartum depressive symptoms experienced by marriage-based
      immigrant mothers in Taiwan. Data were collected at 1 and 6 months postpartum
      from 203 immigrant mothers married to Taiwanese men in Taipei, Taiwan. The
      structural equation modeling results showed that social support and postpartum
      depression were directly and negatively related. Higher social support and lower
      depression at 1 month postpartum were related to a positive social attitude
      (i.e., accepting attitude toward mainstream society). Social attitude was a
      moderator of the relationship between depression at 1 month and social support at
      6 months postpartum, where a positive social attitude decreased the negative
      effect of depression at 1 month on social support at 6 months. Social support in
      the early postpartum period not only directly decreased postpartum depression,
      but also indirectly decreased postpartum depression through improving social
      attitude.

PMID- 22865023
TI  - Antitumor activity of mushroom polysaccharides: a review.
AB  - Mushrooms were considered as a special delicacy by early civilizations and valued
      as a credible source of nutrients including considerable amounts of dietary
      fiber, minerals, and vitamins (in particularly, vitamin D). Mushrooms are also
      recognized as functional foods for their bioactive compounds offer huge
      beneficial impacts on human health. One of those potent bioactives is beta
      glucan, comprising a backbone of glucose residues linked by beta-(1->3)
      glycosidic bonds with attached beta-(1->6) branch points, which exhibits
      antitumor and immunostimulating properties. The commercial pharmaceutical
      products from this polysaccharide source, such as schizophyllan, lentinan,
      grifolan, PSP (polysaccharide-peptide complex) and PSK (polysaccharide-protein
      complex), have shown evident clinical results. The immunomodulating action of
      mushroom polysaccharides is to stimulate natural killer cells, T-cells, B-cells,
      neutrophils, and macrophage dependent immune system responses via differing
      receptors involving dectin-1, the toll-like receptor-2 (a class of proteins that
      play a role in the immune system), scavengers and lactosylceramides. beta-Glucans
      with various structures present distinct affinities toward these receptors to
      trigger different host responses. Basically, their antitumor abilities are
      influenced by the molecular mass, branching configuration, conformation, and
      chemical modification of the polysaccharides. This review aims to integrate the
      information regarding nutritional, chemical and biological aspects of
      polysaccharides in mushrooms, which will possibly be employed to elucidate the
      correlation between their structural features and biological functions.

PMID- 22865024
TI  - The persistence of the fluency-confidence association in problem solving.
AB  - Confidence in answers is known to be sensitive to the fluency with which answers
      come to mind. One aspect of fluency is response latency. Latency is often a valid
      cue for accuracy, showing an inverse relationship with both accuracy rates and
      confidence. The present study examined the independent latency-confidence
      association in problem-solving tasks. The tasks were ecologically valid
      situations in which latency showed no validity, moderate validity, and high
      validity as a predictor of accuracy. In Experiment 1, misleading problems, which
      often elicit initial wrong solutions, were answered in open-ended and multiple
      choice test formats. Under the open-ended test format, latency was absolutely not
      valid in predicting accuracy: Quickly and slowly provided solutions had a similar
      chance of being correct. Under the multiple-choice test format, latency predicted
      accuracy better. In Experiment 2, nonmisleading problems were used; here, latency
      was highly valid in predicting accuracy. A breakdown into correct and incorrect
      solutions allowed examination of the independent latency-confidence relationship
      when latency necessarily had no validity in predicting accuracy. In all
      conditions, regardless of latency's validity in predicting accuracy, confidence
      was persistently sensitive to latency: The participants were more confident in
      solutions provided quickly than in those that involved lengthy thinking. The
      study suggests that the reliability of the latency-confidence association in
      problem solving depends on the strength of the inverse relationship between
      latency and accuracy in the particular task.

PMID- 22865025
TI  - [Value of magnetic resonance imaging in diffuse liver diseases].
AB  - CLINICAL PROBLEM: Diffuse liver diseases show an increasing prevalence. The
      diagnostic gold standard of liver biopsy has several disadvantages. There is a
      clinical demand for non-invasive imaging-based techniques to qualitatively and
      quantitatively evaluate the entire liver. STANDARD RADIOLOGICAL METHODS:
      Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are
      routinely used. METHODICAL INNOVATIONS: Steatosis: chemical shift and frequency
      selective imaging, MR spectroscopy (MRS). Hemochromatosis: MR-based iron
      quantification. Fibrosis: MR elastography, diffusion, intravoxel incoherent
      motion (IVIM) and MR perfusion. PERFORMANCE/ACHIEVEMENTS/PRACTICAL
      RECOMMENDATIONS: T1-weighted in and opposed phase imaging is the clinically most
      frequently used MR technique to noninvasively detect and quantify steatosis. New
      methods for quantification that are not influenced by confounders like iron
      overload are under investigation. The most sensitive method to measure the fat
      content of the liver is MRS. As data acquisition and analysis remain complex and
      there is no whole organ coverage, MRS of the liver is not a routine method. With
      an optimized protocol incorporating T2* sequences, MRI is the modality of choice
      to quantify iron overload in hemochromatosis. Standard MR sequences cannot depict
      early stages of liver fibrosis. Advanced MR techniques (e.g. elastography,
      diffusion, IVIM and perfusion) for noninvasive assessment of liver fibrosis
      appear promising but their role has to be further investigated.

PMID- 22865026
TI  - [Possibilities for exposure reduction in computed tomography examination of acute
      chest pain].
AB  - CLINICAL/METHODICAL ISSUE: Electrocardiogram-gated (ECG) computed tomography (CT)
      investigations can be accompanied by high amounts of radiation exposure. This is
      particularly true for the investigation of patients with unclear and acute chest
      pain. STANDARD RADIOLOGICAL METHODS: The common approach in patients with acute
      chest pain is standard spiral CT of the chest. METHODICAL INNOVATIONS: The chest
      pain or triple-rule-out CT protocol is a relatively new ECG-gated protocol of the
      entire chest. This article reviews and discusses different techniques for the CT
      investigation of patients with acute chest pain. PERFORMANCE: By applying the
      appropriate scan technique, the radiation exposure for an ECG-gated protocol must
      not necessarily be higher than a standard chest CT scan ACHIEVEMENTS: Aortic
      pathologies are far better depicted by ECG-gated scan protocols and depending on
      the heart rate coronary artery disease can also be detected at the same time.
      PRACTICAL RECOMMENDATIONS: The use of ECG-triggered scans will not support the
      diagnostics of the pulmonary arteries. However, in unspecific chest pain an ECG
      triggered scan protocol can provide information on the differential diagnosis.

PMID- 22865027
TI  - Streptomyces erringtonii sp. nov. and Streptomyces kaempferi sp. nov., isolated
      from a hay meadow soil.
AB  - Two filamentous actinomycetes isolated from a hay meadow soil were provisionally
      assigned to the genus Streptomyces based on morphological features. The isolates
      were found to have chemical and morphological properties typical of the genus
      Streptomyces and formed distinct phyletic lines in the 16S rRNA gene tree.
      Isolate I36(T) was most closely related to Streptomyces glauciniger NBRC
      100913(T) and isolate I37(T) to Streptomyces mirabilis NBRC 13450(T). Low DNA:DNA
      relatedness values were recorded between each of the isolates and their closest
      phylogenetic neighbour. The isolates were also distinguished from their nearest
      phylogenetic neighbour, and from one another, using a combination of phenotypic
      properties. These data indicate that the isolates should be recognised as new
      species in the genus Streptomyces. The names proposed for these new taxa are
      Streptomyces erringtonii sp. nov. and Streptomyces kaempferi sp. nov. with
      isolate I36(T) (=CGMCC 4.7016(T) = KACC 15424(T)) and isolate I37(T) (=CGMCC
      4.7020(T) = KACC 15428(T)) as the respective type strains.

PMID- 22865028
TI  - Transformation in follicular lymphoma: biology, prognosis, and therapeutic
      options.
AB  - The transformation of follicular lymphoma to an aggressive lymphoma is a well
      recognised complication that occurs at a rate of approximately 3 % a year for the
      first 10 years of observation. Transformation is accompanied by increased risk of
      refractoriness and a poor expectation of survival. Genetic and epigenetic
      triggers for transformation have been described. Prior to routine use of
      rituximab, transformed lymphoma was managed in a fashion similar to that for de
      novo diffuse large B-cell lymphoma, with generally poor results. Rituximab
      appears to have improved outcomes. Some centres, including our own, use high-dose
      chemotherapy with stem cell transplantation as consolidation for those with
      responsive disease. Here, we focus on transformed follicular lymphoma, and
      provide an overview of the current literature and our approach to management.

PMID- 22865029
TI  - Membrane-damaging potential of natural L-(-)-usnic acid in Staphylococcus aureus.
AB  - The purpose of this investigation was to try to understand the antibacterial
      mechanism of L-(-)-usnic acid isolated for the first time from fruticose lichen
      Usnea subfloridana using clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of L-(-)
      usnic acid against the clinical isolates of MRSA and reference strain S. aureus
      MTCC-96 (SA-96) was in the range 25-50 MUg/ml. Treatment of both reference and
      clinical strains (MRSA-ST 2071) with four-fold MIC concentrations (100-200
      MUg/ml) of L-(-)-usnic acid reduced the viability of cells without damaging the
      cell wall. However, the loss of 260 nm absorbing material and increase in
      propidium iodide uptake was observed in both of the strains. Similarly, a
      combined effect of L-(-)-usnic acid (25-50 MUg/ml) and 7.5 % NaCl resulted in a
      reduced number of viable cells within 24 h in comparison to the control. These
      observations clearly indicate that L-(-)-usnic acid exerts its action by
      disruption of the bacterial membrane. Further, in vivo efficacy showed that L-(-)
      usnic acid significantly (p < 0.001) lowered the microbial load of spleen at
      doses ranging from 1 to 5 mg/kg. Further, toxicity studies in infected mice at
      doses 20 times higher than the efficacious dose indicated L-(-)usnic acid to be
      safe. Paradoxically, L-(-)usnic acid exhibited changes in serum triglycerides,
      alkaline phosphatase (ALKP) and liver organ weight in the healthy mice
      administered with only 25 mg/kg body weight. The results obtained in this study
      showed that natural L-(-)-usnic acid exerts its antibacterial activity against
      MRSA by disruption of the cell membrane. Further, the natural L-(-)-usnic acid
      was found to be safe up to 100 mg/kg body weight, thereby, making it a probable
      candidate for treating S. aureus infections.

PMID- 22865031
TI  - Determination of the total phenolic and anthocyanin contents and antimicrobial
      activity of Viburnum opulus fruit juice.
AB  - Viburnum opulus is a plant with fruits that are rich in biologically active
      substances, making it valuable to the food and pharmaceutical industries. Here,
      we present our study of the total phenolic and anthocyanin contents and
      antimicrobial activity in the fruit juice of six V. opulus L. accessions. The
      cultivar 'Krasnaya Grozd' was notable for its exceptionally large amount of total
      phenolics, 1168 mg/100 g, with anthocyanins comprising 3-5 % of the total
      phenolic content. The evaluation of the antimicrobial properties confirmed that
      the juice of V. opulus fruits strongly inhibited the growth of a wide range of
      human pathogenic bacteria, both Gram-negative (Salmonella typhimurium and S.
      agona) and Gram-positive (Staphylococcus aureus, Lysteria monocytogenes, and
      Enterococcus faecalis) organisms. Conversely, the yeasts Debaryomyces hansenii
      and Torulaspora delbrueckii showed complete resistance to the fruit juice,
      whereas a low sensitivity was demonstrated by Trichosporon cutaneum,
      Kluyveromyces marxianus var. lactis, Saccharomyces cerevisiae, S. cerevisiae 12R,
      and Candida parapsilosis.

PMID- 22865032
TI  - Diagnosis and management of Henoch-Schonlein purpura in pregnancy: a review of
      the literature.
AB  - INTRODUCTION: Henoch-Schonlein Purpura (HSP) is an IgA-mediated hypersensitivity
      vasculitis uncommon in adults and rarely described in pregnancy. So far, only 20
      cases have been described in pregnancy in the worldwide literature. Although
      prognosis for this condition is reported as excellent, most studies are based on
      the paediatric population. Henoch-Schonlein Purpura is known to be more severe in
      adults, and women with a history of HSP have an increased risk of complications
      during pregnancy. Diagnosis and management of HSP in adults is based on limited
      evidence, with little data regarding the obstetric population. MATERIAL AND
      METHODS: Review of data cited in current published cases. CONCLUSION: We review
      the obstetric cases reported so far and discuss diagnostic matters and current
      management strategies.

PMID- 22865033
TI  - A randomized controlled trial comparing parenteral normal saline with and without
      5% dextrose on the course of labor in nulliparous women.
AB  - OBJECTIVE: The objective of this study was to compare intravenous normal saline
      with and without 5% dextrose on the course of labor in nulliparous women in
      active phase of spontaneous labor. STUDY DESIGN: In a randomized controlled
      trial, term, nulliparous women with singleton pregnancy in active labor were
      randomized into one of two groups receiving either normal saline or normal saline
      alternating with 5% dextrose at rate of 175 ml/h. The primary outcome was total
      length of labor from onset of study fluid in vaginally delivered women. Maternal
      and neonatal outcomes were also analyzed. RESULTS: Of 250 women enrolled, in
      vaginally delivered subjects, there was significant difference in the duration of
      labor (p=0.0) and prolonged labor (p=0.01), with favorable results for women in
      5% dextrose alternating with normal saline. No statistically significant
      differences were observed in the cesarean section rates between the groups. The
      cord pH was significantly higher in neonates born to women in 5% dextrose
      alternating with normal saline infusion as compared to normal saline alone
      (p=0.01), however, no neonate in the study had acidemia. CONCLUSION:
      Administration of a 5% dextrose solution alternating with normal saline is a
      better parenteral fluid for significantly decreasing duration of labor in term
      vaginally delivered nulliparous women in spontaneous active labor as compared to
      normal saline alone.

PMID- 22865034
TI  - Endometrial thickness measurement throughout a menstrual cycle in non-obese
      infertile patients with polycystic ovary syndrome.
AB  - PURPOSE: To analyze the changes in the endometrial thickness in infertile
      polycystic ovary syndrome (PCOS) patients throughout an entire menstrual cycle
      and compare the changes to those seen in infertile patients without PCOS.
      METHODS: This prospective, cross-sectional study was conducted in a total of 58
      non-obese, infertile women with PCOS. The endometrial thickness was measured at
      three different times throughout the menstrual cycle by ultrasound. Age- and body
      mass index (BMI)-matched control group consisted of 62 non-obese infertile
      patients without PCOS. Demographic, hormonal and the ultrasonographic
      measurements of the two groups were compared. RESULTS: Day 3 levels of LH were
      significantly different between the groups (p=0.013). Ovarian volume measurement
      was significant between the groups (p=0001). All the endometrial thickness
      measurements in the early, mid-cycle and late luteal phases were also
      significantly different; p=0.001 for all. CONCLUSION: The study demonstrated an
      increased endometrial stripe measurements throughout a menstrual cycle in
      infertile patients with PCOS, when compared to infertile patients without PCOS.

PMID- 22865035
TI  - Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch
      syndrome (LS).
AB  - BACKGROUND: LS women have a 40-60% lifetime risk of endometrial cancer (EC). Most
      international guidelines recommend screening. However, data on efficacy are
      limited. PURPOSE: To assess the performance of OHES for EC screening in LS and
      compare it with transvaginal ultrasound (TVS) alone. METHODS: A prospective
      observational cohort study of LS women attending a tertiary high-risk familial
      gynaecological cancer clinic was conducted. LS women opting for EC screening
      underwent annual OHES and TVS. Histopathological specimens were processed using a
      strict protocol. Data of women screened between October 2007 and March 2010 were
      analysed from a bespoke database. Histology was used as the gold standard.
      Diagnostic accuracy of OHES was compared with TVS using specificity, and positive
      (PLR) and negative (NLR) likelihood ratios. RESULTS: Forty-one LS women underwent
      69 screens (41 prevalent, 28 incident). Four (three prevalent, one incident)
      women were detected to have EC/atypical endometrial hyperplasia (AEH), five had
      endometrial polyps and two had endometrial hyperplasia (EH) on OHES. TVS detected
      two of four EC/AEH. OHES had similar specificity of 89.8% (CI 79.2, 96.2%), but
      higher PLR 9.8 (CI 4.6, 21) and lower NLR (zero) compared to TVS: specificity
      84.75%(CI 73, 92.8%), PLR 3.28 (CI 1.04, 10.35) and NLR 0.59 (CI 0.22, 1.58). No
      interval cancers occurred over a median follow-up of 22 months. The annual
      incidence was 3.57% (CI 0.09, 18.35) for EC, 10.71% (CI 2.27, 28.23) for polyps
      and 21.4% (CI 8.3, 40.1) for any endometrial pathology. CONCLUSIONS: Our findings
      suggest that in LS, annual OHES is acceptable and has high diagnostic accuracy
      for EC/AEH screening. Larger international studies are needed for confirmation,
      given the relatively small numbers of LS women at individual centres. It
      reinforces the current recommendation that endometrial sampling is crucial when
      screening these women.

PMID- 22865036
TI  - Assessment of cervical intraepithelial neoplasia (CIN) with colposcopic biopsy
      and efficacy of loop electrosurgical excision procedure (LEEP).
AB  - PURPOSE: Conization for suspected high grade cervical intraepithelial neoplasia
      (CIN) is often performed based on abnormal cytology only. Loop electrosurgical
      excision procedure (LEEP) is a very common technique in this context. The present
      study analyses the accuracy of preoperative assessment of CIN with cytology plus
      colposcopic biopsy and assesses the efficacy of LEEP for the treatment of CIN.
      METHODS: Two-hundred and sixty-six consecutive patients treated with LEEP for
      suspected CIN at our center were retrospectively analyzed. Cytology, HPV-DNA
      testing, colposcopically directed cervical biopsy and/or endocervical curettage
      were performed to assess cervical lesions before and 3-6 months after surgery.
      RESULTS: Median age of the patients was 34 years. Median follow-up was 50 months.
      Preoperative HPV testing was positive for high risk types in 77.9%. All patients
      underwent LEEP without further ablative procedures. Complete excision of the
      lesion could be achieved in 84.3%; in 13.5% margins were not securely cleared and
      in 2.2% the lesion was not excised entirely. Overall complication rate was 5.4%
      (mainly postoperative bleeding and pain). Overall concordance of colposcopic
      biopsy and cone histology was 85.8%. The concordance rate was higher for CIN 2/3
      (95.1%) compared with CIN 1 (63.2%). Nine patients (3.4%) had persistent disease
      after 3 months, 4 (1.5%) developed disease recurrence and underwent re
      conization. HPV testing at 3-6 months after surgery was negative in 78.5%; 2 of
      the patients developing disease recurrence had a persistent HPV infection after
      surgery. CONCLUSIONS: Assessment of cervical lesions with colposcopic biopsy is
      an accurate method (concordance with cone histology 85.8%). Surgical treatment of
      high grade CIN with LEEP is a safe procedure with low recurrence rates, resulting
      in a clearance of cervical HPV infection in the majority of cases.

PMID- 22865037
TI  - Serum Fetuin-A levels in women with polycystic ovary syndrome.
AB  - PURPOSE: The liver-derived Fetuin-A (alpha2-Heremans Schmid glycoprotein) is a
      circulating glycoprotein that may be related to insulin resistance and polycystic
      ovary syndrome (PCOS). We aimed to investigate the Fetuin-A levels in patients
      with PCOS. METHODS: A total of 88 women were included in the study. We measured
      the Fetuin-A levels in 44 women with PCOS and compared with 44 healthy women.
      RESULTS: The mean age in control group was 28.61+/-5.0 (18-38) and 25.5+/-4.1 (17
      36) in PCOS group. While there was statistically significant difference in terms
      of age and testosterone levels, there was no difference in terms of smoking
      status and BMI between the groups. Accordingly, women with PCOS were older than
      controls [28.61+/-5.0 (18-38) and 25.5+/-4.1 (17-36), respectively, p=0.002]. The
      mean Fetuin-A level of PCOS group was 255.4+/-37.2 (203.1-388.9) ng/mL and the
      mean Fetuin-A level of control group was 253.0+/-43.2 (179.9-355.4) ng/mL. There
      was no difference between the groups with regard to Fetuin-A, before and after
      adjustment for age (p values 0.780 and 0.835, respectively). CONCLUSIONS: Serum
      Fetuin-A levels of women with PCOS did not change in comparison with the healthy
      controls.

PMID- 22865038
TI  - Severe Sirenomelia following frozen-thawed embryo transfer cycle.

PMID- 22865039
TI  - Bell's palsy in pregnancy.

PMID- 22865040
TI  - How to maximize the aspect ratio of clay nanoplatelets.
AB  - Melt-synthesis yielded lithium-fluorohectorites (Li-hect(x)) with variable layer
      charge (x = 0.4, 0.6, 0.8, 1.0). Counterintuitively, both tactoid diameter and
      intracrystalline reactivity increased concomitantly with increasing layer charge.
      This way hectorites with very large diameters were obtained (d(50%) = 48 MUm)
      that nevertheless still spontaneously delaminate when immersed into water and
      nano-platelets with huge aspect ratios (>10 000) are formed. Melt-synthesis of Li
      hect(x) has been performed in an open glassy carbon crucible allowing for easy
      scaling to batches of 500 g. These unprecedented huge aspect ratio fillers
      promise great potential for flame retardants and barrier applications.

PMID- 22865043
TI  - Transcriptional control of innate lymphoid cells.
AB  - Cells that belong to the family of innate lymphoid cells (ILCs) not only form a
      first line of defense against invading microbes, but also play essential roles in
      tissue remodeling and immune pathology. Rorgammat(+)  ILCs, producing the
      cytokines IL-22 and IL-17, include lymphoid tissue inducer (LTi) cells which are
      critical for the formation of lymphoid structures. Recently another ILC subset
      has been identified, which is dependent on RORalpha for its development and is
      dedicated to the production of the Th2 cytokines IL-5 and IL-13. These ILCs have
      been termed type 2 ILCs. All ILC subets are considered to belong to the same
      family that also includes natural killer cells because they all rely on the
      common gamma-chain (gammac) of the IL-2 receptor for their development and
      function, share a lymphoid morphology and depend on the transcriptional repressor
      Id2 for their development. Other transcription factors, including Notch, and the
      aryl hydrocarbon receptor (AhR) in RORgammat(+)  ILCs and GATA3 in type 2 ILCs,
      also play roles in the development, survival, and function of these ILC
      subpopulations. Here we review the current knowledge with regard to the
      transcription factors involved in the development and functions of ILCs.

PMID- 22865044
TI  - Indoleamine 2,3-dioxygenase: from catalyst to signaling function.
AB  - Control of tryptophan metabolism by indoleamine 2,3-dioxygenase (IDO) in
      dendritic cells (DCs) is a highly versatile regulator of innate and adaptive
      immune responses. In acute reactions, the otherwise inflammatory cytokine
      interferon gamma (IFN-gamma) acts in a feedback fashion to induce IDO's enzymatic
      function--and thus prevent potentially harmful, exaggerated responses--through
      the combined effects of tryptophan starvation and tryptophan catabolites acting
      via the aryl hydrocarbon receptor of T cells. IDO, however, is also involved in
      the maintenance of stable tolerance to self in noninflammatory contexts, thus
      restraining autoimmunity. Exposure, indeed, of mouse plasmacytoid DCs (pDCs) to
      transforming growth factor beta (TGF-beta) provides IDO with regulatory effects
      that are distinct, in nature, from its enzymic activity. Once phosphorylated, IDO
      mediates signaling events culminating in self-amplification and maintenance of a
      stably regulatory condition in pDCs. Therefore, IDO has dual immunoregulatory
      functions driven by distinct cytokines. Firstly, the IFN-gamma-IDO axis is
      crucial in generating and sustaining the function of regulatory T cells.
      Secondly, a nonenzymic function of IDO--as a signaling molecule--contributes to
      TGF-beta-driven tolerance. The latter function is part of a regulatory circuit in
      pDCs whereby--in response to TGF-beta--the kinase Fyn mediates tyrosine
      phosphorylation of IDO-associated immunoreceptor tyrosine-based inhibitory
      motifs, resulting in downstream effects that regulate gene expression and preside
      over a proper, homeostatic balance between immunity and tolerance. All these
      aspects are covered in this review.

PMID- 22865045
TI  - MKP-1: a critical phosphatase in the biology of macrophages controlling the
      switch between proliferation and activation.
AB  - Macrophages play a central role in the immune response. These cells either
      proliferate in response to, for example, growth factors or become activated in
      response to, for example, LPS and develop functional activities. Experiments
      carried out in mice showed that macrophage proliferation requires a short period
      of ERK phosphorylation, while an extended period is required for macrophage
      activation. The length of phosphorylation is controlled by the MAPK phosphatase-1
      (MKP-1), a nuclear-localized dual-specificity phosphatase that dephosphorylates
      the MAPKs ERK, p38, and c-Jun NH(2) -terminal kinase (JNK). MKP-1 is induced in
      macrophages by growth factors, as well as by activators such as LPS, but with
      different kinetics; to achieve the different functional outcomes (proliferation
      versus activation), the inhibition of MKP-1 by cytokines such as IFN-gamma blocks
      macrophage proliferation and induces activation. The data presented in this
      review show that this phosphatase is the switch between macrophage proliferation
      and activation.

PMID- 22865047
TI  - Copy number variation in autoimmunity--importance hidden in complexity?
AB  - Copy number variation, namely regions of the genome that can be either deleted or
      duplicated in a variable way, has emerged as an important source of genetic
      variance in the human genome. Genes with immunological functions are particularly
      prone to copy number variation, in part because this is a mechanism to expand the
      recognition repertoire; however, immunological genes not directly involved in
      immune recognition are also copy number variable but, despite the link between
      immunological function and copy number variation, very few copy number variants
      (CNVs) have been found to be associated with autoimmune diseases, even in recent
      large genome-wide CNV-association studies. Nonetheless, CNVs in FCGR3B, DEFB4,
      CCL3L1, C4A/B and NCF1 have been suggested to be associated with autoimmune
      diseases, although there is conflicting evidence in all cases. The reasons for
      the lack of definitive data on CNV-autoimmunity associations, as well as the
      technical challenges for the field are the focus of this review.

PMID- 22865046
TI  - New helping friends for B cells.
AB  - Over the past decade, a growing recognition of the importance of neutralizing
      antibodies in host defense combined with the success of B-cell depletion
      therapies in treating auto-immune disorders has led to an increased focus on
      better understanding the pathways underpinning B-cell antibody production. In
      general, B cells require cognate interaction with T helper cells in the germinal
      center of lymphoid follicles to generate protective antibodies. However, recent
      evidence shows that B cells receive additional help from invariant natural killer
      T cells, dendritic cells, and various granulocytes, including neutrophils,
      eosinophils, and basophils. These innate immune cells enhance T-cell-dependent
      antibody responses by delivering B-cell helper signals both in the germinal
      center and at postgerminal center lymphoid sites such as the bone marrow. In
      addition to enhancing and complementing the B-cell helper activity of canonical T
      cells, invariant natural killer T cells, dendritic cells, and granulocytes can
      deliver T cell-independent B-cell helper signals at the mucosal interface and in
      the marginal zone of the spleen to initiate rapid innate-like antibody responses.
      Here, we discuss recent advances in the role of adaptive and innate B-cell helper
      signals in antibody diversification and production.

PMID- 22865048
TI  - T(FH) memory: more or less T(FH)?
AB  - Follicular T-helper (T(FH) ) cells are a subset of CD4(+)  T cells that is
      specialized to help B cells. Their capacity to give rise to enhanced T(FH) 
      memory responses has not been documented. A study by Weber et al. [Eur. J.
      Immunol. 2012 42: 1981-1988] in this issue of the European Journal of Immunology
      addresses this question, and a picture is emerging from this and several other
      recent studies which suggests that the formation of memory T(FH)  and of central
      memory (T(CM) ) cells are intimately bound and that the heterogeneity of what we
      currently call "T(FH) '' cells clouds this issue. In this Commentary, we discuss
      these complexities and ask what memory T(FH)  cells are doing given that the
      germinal centers are a feature of primary, but not secondary immune responses.

PMID- 22865049
TI  - IFN-gamma receptor deficiency prevents diabetes induction by diabetogenic CD4+,
      but not CD8+, T cells.
AB  - IFN-gamma is generally believed to be important in the autoimmune pathogenesis of
      type 1 diabetes (T1D). However, the development of spontaneous beta-cell
      autoimmunity is unaffected in NOD mice lacking expression of IFN-gamma or the IFN
      gamma receptor (IFNgammaR), bringing into question the role IFN-gamma has in T1D.
      In the current study, an adoptive transfer model was employed to define the
      contribution of IFN-gamma in CD4(+) versus CD8(+) T cell-mediated beta-cell
      autoimmunity. NOD.scid mice lacking expression of the IFNgammaR beta chain
      (NOD.scid.IFNgammaRB(null)) developed diabetes following transfer of beta cell
      specific CD8(+) T cells alone. In contrast, beta cell-specific CD4(+) T cells
      alone failed to induce diabetes despite significant infiltration of the islets in
      NOD.scid.IFNgammaRB(null) recipients. The lack of pathogenicity of CD4(+) T-cell
      effectors was due to the resistance of IFNgammaR-deficient beta cells to
      inflammatory cytokine-induced cell death. On the other hand, CD4(+) T cells
      indirectly promoted beta-cell destruction by providing help to CD8(+) T cells in
      NOD.scid.IFNgammaRB(null) recipients. These results demonstrate that IFN-gammaR
      may play a key role in CD4(+) T cell-mediated beta-cell destruction.

PMID- 22865050
TI  - Paxillin phosphorylation by JNK and p38 is required for NFAT activation.
AB  - Paxillin is an adaptor protein associated with focal adhesion complex, and is
      activated by tyrosine phosphorylation through focal adhesion kinase (FAK) and Src
      kinase. Recent studies reveal that serine phosphorylation of paxillin by JNK and
      p38 MAPK is essential for cell migration or neurite extension, but their cellular
      targets remain unclear. In this study, we examined the requirement of paxillin
      phosphorylation by p38 MAPK or JNK in T-cell motility and activation using
      paxillin mutants at the respective phosphorylation sites, Ser85, and Ser178.
      (S85A)-paxillin, (S178A)-paxillin, or (S85A/S178A)-paxillin inhibited the
      motility of NIH/3T3 fibroblasts, but did not interfere with T-cell migration and
      integrin-mediated T-cell adhesion. In contrast, activation of T cells was
      effectively suppressed by (S85A/S178A)-paxillin. Transgenic (S85A/S178A)-paxillin
      expression inhibited T-cell proliferation and reduced the production of IL-2, IFN
      gamma, and IL-4. In searching for signals modulated by (S85A/S178A)-paxillin, we
      found that NFAT activation was specifically blocked by (S85A/S178A)-paxillin.
      This could be partly attributed to diminished stromal interaction molecule 1
      (STIM1) expression and attenuated TCR-induced Ca(2+)  influx. Our results
      demonstrate that dual phosphorylation of paxillin by JNK and p38 MAPK is
      essential for T-cell activation and suggest that NFAT is a functional target of
      the JNK/p38 phosphorylated paxillin.

PMID- 22865051
TI  - From China to Glasgow.

PMID- 22865054
TI  - Value of multidetector computed tomography for the radiologic grading of
      sacroiliitis in ankylosing spondylitis.
AB  - The objective of this study is to investigate the value of multidetector computed
      tomography (MDCT) in the assessment of sacroiliitis in patients with established
      ankylosing spondylitis (AS). Paired plain radiographs and MDCT images of the 330
      sacroiliac (SI) joints in 165 patients with definite or probable ankylosing
      spondylitis were analyzed for sacroiliitis. Sacroiliitis on plain radiographs
      were graded on a scale of 0-4 according to the modified New York (NY) criteria.
      For grading of sacroiliitis by MDCT, modified NY criteria were revised for MDCT
      application introducing the concept of quantification. The relationship between
      sacroiliitis grades by plain radiography and MDCT was analyzed by two
      radiologists, blinded for all clinical data. Of the 330 SI joints assessed, there
      was agreement between the sacroiliitis grading by plain radiography and MDCT in
      73 (22.1 %) SI joints. Sacroiliitis grade by MDCT was higher in 250 (75.8 %) SI
      joints and lower in 7 (2.1 %) SI joints than that by plain radiography. Using the
      MDCT, 83.6 % of patients met the modified NY radiologic criteria for the
      classification of AS, compared with 58.2 % of the patients by plain radiography.
      Twenty-six percent of the patients, who did not meet the modified NY criteria for
      the classification of AS by plain radiography, met the criteria by MDCT. Disease
      durations in patients with grade 2 and grade 3 sacroiliitis were significantly
      shorter in patients evaluated by MDCT compared with plain radiography. MDCT is a
      useful imaging method that can be applied to the initial diagnosis of the AS, and
      by better visualization of SI joint changes, it can be used to predict the
      progress of the disease.

PMID- 22865055
TI  - A case of dermatomyositis accompanied by spontaneous intramuscular hemorrhage
      despite normal coagulability.

PMID- 22865057
TI  - Single stage transcranial exposure of large dural venous sinuses for surgically
      assisted direct transvenous embolization of high-grade dural arteriovenous
      fistulas: technical note.
AB  - BACKGROUND: High-grade dural arteriovenous fistulas (DAVFs) with retrograde
      cortical leptomeningeal drainage are formidable lesions because of their risk for
      intracranial hemorrhage. Treatment is aimed at occluding venous outflow to
      achieve obliteration of the fistula. In DAVFs that involve a large dural venous
      sinus (transverse sigmoid sinus or superior sagittal sinus), occluding venous
      outflow can be accomplished endovascularly with transvenous embolization.
      However, in some cases of DAVFs with reflux into cortical leptomeningeal veins,
      there may be venous restrictive disease downstream, such as occlusive thrombosis,
      which can prohibit endovascular access via the transfemoral or transjugular
      routes. In these instances, a transcranial approach can be performed to expose
      the large dural venous sinus distal to the site of occlusion for direct
      catheterization of the venous outflow for transvenous embolization. This combined
      surgical and endovascular strategy provides direct access to the venous outflow
      and bypasses the site of thrombotic obstruction. METHODS: In this report, we
      describe our technique of single stage surgically-assisted transvenous
      embolization in three patients with high-grade DAVFs involving a large dural
      sinus. RESULTS: All patients achieved complete obliteration of their DAVFs
      without any venous related complications. CONCLUSION: Our technique of surgically
      assisted direct transvenous embolization of high-grade DAVFs can be successfully
      performed as a single stage in the operating room with intraoperative angiography
      and stereotactic image guidance.

PMID- 22865058
TI  - Synergistic activation of the pathogenicity-related proline iminopeptidase gene
      in Xanthomonas campestris pv. campestris by HrpX and a LuxR homolog.
AB  - Xanthomonas campestris pv. campestris strain 8004 contains an orphan quorum
      sensing (QS) locus, xccR-pip(Xcc), in which the proline iminopeptidase (pip(Xcc))
      gene (where "Xcc" indicates that the pip gene is from X. campestris pv.
      campestris) is positively regulated by the LuxR homologue XccR by binding to the
      luxXc box of the pip(Xcc) promoter. The disruption of pip(Xcc) significantly
      attenuated the virulence of X. campestris pv. campestris. An imperfect plant
      inducible promoter (PIP) box is located in the upstream region of the pip(Xcc)
      promoter, which is the putative binding site of the transcriptional activator
      HrpX. To explore whether the expression of the pip(Xcc) gene is regulated by
      HrpX, the expression level of a pip(Xcc) promoter-gusA fusion gene was assayed in
      an hrpX disruption mutant. The results showed that the lack of HrpX dramatically
      decreased the beta-glucuronidase (GUS) activity. Further analyses using an
      electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP)-PCR indicated that the imperfect PIP box in X. campestris pv. campestris
      is specifically bound to HrpX. These data demonstrated that the pip(Xcc) gene
      belongs to the hrp regulon and that the imperfect PIP box of the pip(Xcc)
      promoter could be a cis element for the HrpX protein. We further showed in a
      pulldown assay that XccR can bind HrpX, suggesting that these two regulatory
      proteins coactivate the virulence factor by binding to the different cis elements
      of the pip(Xcc) gene and adapt to the host environment during X. campestris pv.
      campestris infection.

PMID- 22865059
TI  - Structure-based engineering of methionine residues in the catalytic cores of
      alkaline amylase from Alkalimonas amylolytica for improved oxidative stability.
AB  - This work aims to improve the oxidative stability of alkaline amylase from
      Alkalimonas amylolytica through structure-based site-directed mutagenesis. Based
      on an analysis of the tertiary structure, five methionines (Met 145, Met 214, Met
      229, Met 247, and Met 317) were selected as the mutation sites and individually
      replaced with leucine. In the presence of 500 mM H(2)O(2) at 35 degrees C for 5
      h, the wild-type enzyme and the M145L, M214L, M229L, M247L, and M317L mutants
      retained 10%, 28%, 46%, 28%, 72%, and 43% of the original activity, respectively.
      Concomitantly, the alkaline stability, thermal stability, and catalytic
      efficiency of the M247L mutant were also improved. The pH stability of the
      mutants (M145L, M214L, M229L, and M317L) remained unchanged compared to that of
      the wild-type enzyme, while the stable pH range of the M247L mutant was extended
      from pH 7.0 to 11.0 for the wild type to pH 6.0 to 12.0 for the mutant. The wild
      type enzyme lost its activity after incubation at 50 degrees C for 2 h, and the
      M145L, M214L, M229L, and M317L mutants retained less than 14% of the activity,
      whereas the M247L mutant retained 34% of the activity under the same conditions.
      Compared to the wild-type enzyme, the k(cat) values of the M145L, M214L, M229L,
      and M317L mutants decreased, while that of the M247L mutant increased slightly
      from 5.0 * 10(4) to 5.6 * 10(4) min(-1). The mechanism responsible for the
      increased oxidative stability, alkaline stability, thermal stability, and
      catalytic efficiency of the M247L mutant was further analyzed with a structure
      model. The combinational mutants were also constructed, and their biochemical
      properties were characterized. The resistance of the wild-type enzyme and the
      mutants to surfactants and detergents was also investigated. Our results indicate
      that the M247L mutant has great potential in the detergent and textile
      industries.

PMID- 22865056
TI  - Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical
      pathways, and networks.
AB  - Memory deficits are prominent features of mild cognitive impairment (MCI) and
      Alzheimer's disease (AD). The genetic architecture underlying these memory
      deficits likely involves the combined effects of multiple genetic variants
      operative within numerous biological pathways. In order to identify functional
      pathways associated with memory impairment, we performed a pathway enrichment
      analysis on genome-wide association data from 742 Alzheimer's Disease
      Neuroimaging Initiative (ADNI) participants. A composite measure of memory was
      generated as the phenotype for this analysis by applying modern psychometric
      theory to item-level data from the ADNI neuropsychological test battery. Using
      the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways
      with enrichment (FDR-corrected p-value < 0.05) against this composite memory
      score. Processes classically understood to be involved in memory consolidation,
      such as neurotransmitter receptor-mediated calcium signaling and long-term
      potentiation, were highly represented among the enriched pathways. In addition,
      pathways related to cell adhesion, neuronal differentiation and guided outgrowth,
      and glucose- and inflammation-related signaling were also enriched. Among genes
      that were highly-represented in these enriched pathways, we found indications of
      coordinated relationships, including one large gene set that is subject to
      regulation by the SP1 transcription factor, and another set that displays co
      localized expression in normal brain tissue along with known AD risk genes. These
      results 1) demonstrate that psychometrically-derived composite memory scores are
      an effective phenotype for genetic investigations of memory impairment and 2)
      highlight the promise of pathway analysis in elucidating key mechanistic targets
      for future studies and for therapeutic interventions.

PMID- 22865060
TI  - A wide variety of Clostridium perfringens type A food-borne isolates that carry a
      chromosomal cpe gene belong to one multilocus sequence typing cluster.
AB  - Of 98 suspected food-borne Clostridium perfringens isolates obtained from a
      nationwide survey by the Food and Consumer Product Safety Authority in The
      Netherlands, 59 strains were identified as C. perfringens type A. Using PCR-based
      techniques, the cpe gene encoding enterotoxin was detected in eight isolates,
      showing a chromosomal location for seven isolates and a plasmid location for one
      isolate. Further characterization of these strains by using (GTG)(5) fingerprint
      repetitive sequence-based PCR analysis distinguished C. perfringens from other
      sulfite-reducing clostridia but did not allow for differentiation between various
      types of C. perfringens strains. To characterize the C. perfringens strains
      further, multilocus sequence typing (MLST) analysis was performed on eight
      housekeeping genes of both enterotoxic and non-cpe isolates, and the data were
      combined with a previous global survey covering strains associated with food
      poisoning, gas gangrene, and isolates from food or healthy individuals. This
      revealed that the chromosomal cpe strains (food strains and isolates from food
      poisoning cases) belong to a distinct cluster that is significantly distant from
      all the other cpe plasmid-carrying and cpe-negative strains. These results
      suggest that different groups of C. perfringens have undergone niche
      specialization and that a distinct group of food isolates has specific core
      genome sequences. Such findings have epidemiological and evolutionary
      significance. Better understanding of the origin and reservoir of enterotoxic C.
      perfringens may allow for improved control of this organism in foods.

PMID- 22865061
TI  - Genotyping of present-day and historical Geobacillus species isolates from milk
      powders by high-resolution melt analysis of multiple variable-number tandem
      repeat loci.
AB  - Spores of thermophilic Geobacillus species are a common contaminant of milk
      powder worldwide due to their ability to form biofilms within processing plants.
      Genotyping methods can provide information regarding the source and monitoring of
      contamination. A new genotyping method was developed based on multilocus variable
      number tandem-repeat (VNTR) analysis (MLVA) in conjunction with high-resolution
      melt analysis (MLV-HRMA) and compared to the currently used method, randomized
      amplified polymorphic DNA PCR (RAPD-PCR). Four VNTR loci were identified and used
      to genotype 46 Geobacillus isolates obtained from retailed powder and samples
      from 2 different milk powder processing plants. These 46 isolates were
      differentiated into 16 different groups using MLV-HRMA (D = 0.89). In contrast,
      only 13 RAPD-PCR genotypes were identified among the 46 isolates (D = 0.79). This
      new method was then used to analyze 35 isolates obtained from powders with high
      spore counts (>10(4) spores . g(-1)) from a single processing plant together with
      27 historical isolates obtained from powder samples processed in the same region
      of Australia 17 years ago. Results showed that three genotypes can coexist in a
      single processing run, while the same genotypes observed 17 years ago are present
      today. While certain genotypes could be responsible for powders with high spore
      counts, there was no correlation to specific genotypes being present in powder
      plants and retailed samples. In conclusion, the MLV-HRMA method is useful for
      genotyping Geobacillus spp. to provide insight into the prevalence and
      persistence of certain genotypes within milk powder processing plants.

PMID- 22865062
TI  - Sugarcane growth promotion by the endophytic bacterium Pantoea agglomerans 33.1.
AB  - The promotion of sugarcane growth by the endophytic Pantoea agglomerans strain
      33.1 was studied under gnotobiotic and greenhouse conditions. The green
      fluorescent protein (GFP)-tagged strain P. agglomerans 33.1::pNKGFP was monitored
      in vitro in sugarcane plants by microscopy, reisolation, and quantitative PCR
      (qPCR). Using qPCR and reisolation 4 and 15 days after inoculation, we observed
      that GFP-tagged strains reached similar density levels both in the rhizosphere
      and inside the roots and aerial plant tissues. Microscopic analysis was performed
      at 5, 10, and 18 days after inoculation. Under greenhouse conditions, P.
      agglomerans 33.1-inoculated sugarcane plants presented more dry mass 30 days
      after inoculation. Cross-colonization was confirmed by reisolation of the GFP
      tagged strain. These data demonstrate that 33.1::pNKGFP is a superior colonizer
      of sugarcane due to its ability to colonize a number of different plant parts.
      The growth promotion observed in colonized plants may be related to the ability
      of P. agglomerans 33.1 to synthesize indoleacetic acid and solubilize phosphate.
      Additionally, this strain may trigger chitinase and cellulase production by plant
      roots, suggesting the induction of a plant defense system. However, levels of
      indigenous bacterial colonization did not vary between inoculated and
      noninoculated sugarcane plants under greenhouse conditions, suggesting that the
      presence of P. agglomerans 33.1 has no effect on these communities. In this
      study, different techniques were used to monitor 33.1::pNKGFP during sugarcane
      cross-colonization, and our results suggested that this plant growth promoter
      could be used with other crops. The interaction between sugarcane and P.
      agglomerans 33.1 has important benefits that promote the plant's growth and
      fitness.

PMID- 22865063
TI  - Engineering a cyanobacterial cell factory for production of lactic acid.
AB  - Metabolic engineering of microorganisms has become a versatile tool to facilitate
      production of bulk chemicals, fuels, etc. Accordingly, CO(2) has been exploited
      via cyanobacterial metabolism as a sustainable carbon source of biofuel and
      bioplastic precursors. Here we extended these observations by showing that
      integration of an ldh gene from Bacillus subtilis (encoding an l-lactate
      dehydrogenase) into the genome of Synechocystis sp. strain PCC6803 leads to l
      lactic acid production, a phenotype which is shown to be stable for prolonged
      batch culturing. Coexpression of a heterologous soluble transhydrogenase leads to
      an even higher lactate production rate and yield (lactic acid accumulating up to
      a several-millimolar concentration in the extracellular medium) than those for
      the single ldh mutant. The expression of a transhydrogenase alone, however,
      appears to be harmful to the cells, and a mutant carrying such a gene is rapidly
      outcompeted by a revertant(s) with a wild-type growth phenotype. Furthermore, our
      results indicate that the introduction of a lactate dehydrogenase rescues this
      phenotype by preventing the reversion.

PMID- 22865064
TI  - Influence of seasonal and geochemical changes on the geomicrobiology of an iron
      carbonate mineral water spring.
AB  - Fuschna Spring in the Swiss Alps (Engadin region) is a bicarbonate iron(II)-rich,
      pH-neutral mineral water spring that is dominated visually by dark green
      microbial mats at the side of the flow channel and orange iron(III)
      (oxyhydr)oxides in the flow channel. Gradients of O(2), dissolved iron(II), and
      bicarbonate establish in the water. Our goals were to identify the dominating
      biogeochemical processes and to determine to which extent changing geochemical
      conditions along the flow path and seasonal changes influence mineral identity,
      crystallinity, and microbial diversity. Geochemical analysis showed microoxic
      water at the spring outlet which became fully oxygenated within 2.3 m downstream.
      X-ray diffraction and Mossbauer spectroscopy revealed calcite (CaCO(3)) and
      ferrihydrite [Fe(OH)(3)] to be the dominant minerals which increased in
      crystallinity with increasing distance from the spring outlet. Denaturing
      gradient gel electrophoresis banding pattern cluster analysis revealed that the
      microbial community composition shifted mainly with seasons and to a lesser
      extent along the flow path. 16S rRNA gene sequence analysis showed that microbial
      communities differ between the flow channel and the flanking microbial mat.
      Microbial community analysis in combination with most-probable-number analyses
      and quantitative PCR (qPCR) showed that the mat was dominated by cyanobacteria
      and the channel was dominated by microaerophilic Fe(II) oxidizers (1.97 * 10(7)
      +/- 4.36 * 10(6) 16S rRNA gene copies g(-1) using Gallionella-specific qPCR
      primers), while high numbers of Fe(III) reducers (10(9) cells/g) were identified
      in both the mat and the flow channel. Phototrophic and nitrate-reducing Fe(II)
      oxidizers were present as well, although in lower numbers (10(3) to 10(4)
      cells/g). In summary, our data suggest that mainly seasonal changes caused
      microbial community shifts, while geochemical gradients along the flow path
      influenced mineral crystallinity.

PMID- 22865065
TI  - Vip3C, a novel class of vegetative insecticidal proteins from Bacillus
      thuringiensis.
AB  - Three vip3 genes were identified in two Bacillus thuringiensis Spanish
      collections. Sequence analysis revealed a novel Vip3 protein class (Vip3C).
      Preliminary bioassays of larvae from 10 different lepidopteran species indicated
      that Vip3Ca3 caused more than 70% mortality in four species after 10 days at 4
      MUg/cm(2).

PMID- 22865066
TI  - The type 3 protein secretion system of Cupriavidus taiwanensis strain LMG19424
      compromises symbiosis with Leucaena leucocephala.
AB  - Cupriavidus taiwanensis forms proficient symbioses with a few Mimosa species.
      Inactivation of a type III protein secretion system (T3SS) had no effect on
      Mimosa pudica but allowed C. taiwanensis to establish chronic infections and fix
      nitrogen in Leucaena leucocephala. Unlike what was observed for other rhizobia,
      glutamate rather than plant flavonoids mediated transcriptional activation of
      this atypical T3SS.

PMID- 22865067
TI  - Comparison of the multiple-sample means with composite sample results for fecal
      indicator bacteria by quantitative PCR and culture.
AB  - Few studies have addressed the efficacy of composite sampling for measuring
      indicator bacteria by quantitative PCR (qPCR). We compared results from
      composited samples with multiple-sample means for culture- and qPCR-based water
      quality monitoring. Results from composited samples for both methods were
      similarly correlated to multiple-sample means and predicted criteria exceedances
      equally.

PMID- 22865068
TI  - Increased penicillin production in Penicillium chrysogenum production strains via
      balanced overexpression of isopenicillin N acyltransferase.
AB  - Intense classical strain improvement has yielded industrial Penicillium
      chrysogenum strains that produce high titers of penicillin. These strains contain
      multiple copies of the penicillin biosynthesis cluster encoding the three key
      enzymes: delta-(l-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS),
      isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The
      phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme
      responsible for the activation of the side chain precursor phenylacetic acid is
      localized elsewhere in the genome in a single copy. Since the protein level of
      IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting
      step in high-yielding strains. Here, we show that penicillin production in high
      yielding strains can be further improved by the overexpression of IAT while at
      very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates.
      Overproduction of PCL only marginally stimulates penicillin production. These
      data demonstrate that in high-yielding strains IAT is the limiting factor and
      that this limitation can be alleviated by a balanced overproduction of this
      enzyme.

PMID- 22865069
TI  - Altered large-ring cyclodextrin product profile due to a mutation at Tyr-172 in
      the amylomaltase of Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum amylomaltase (CgAM) catalyzes the formation of large
      ring cyclodextrins (LR-CDs) with a degree of polymerization of 19 and higher. The
      cloned CgAM gene was ligated into the pET-17b vector and used to transform
      Escherichia coli BL21(DE3). Site-directed mutagenesis of Tyr-172 in CgAM to
      alanine (Y172A) was performed to determine its role in the control of LR-CD
      production. Both the recombinant wild-type (WT) and Y172A enzymes were purified
      to apparent homogeneity and characterized. The Y172A enzyme exhibited lower
      disproportionation, cyclization, and hydrolysis activities than the WT. The
      k(cat)/K(m) of the disproportionation reaction of the Y172A enzyme was 2.8-fold
      lower than that of the WT enzyme. The LR-CD product profile from enzyme catalysis
      depended on the incubation time and the enzyme concentration. Interestingly, the
      Y172A enzyme showed a product pattern different from that of the WT CgAM at a
      long incubation time. The principal LR-CD products of the Y172A mutated enzyme
      were a cycloamylose mixture with a degree of polymerization of 28 or 29 (CD28 or
      CD29), while the principal LR-CD product of the WT enzyme was CD25 at 0.05 U of
      amylomaltase. These results suggest that Tyr-172 plays an important role in
      determining the LR-CD product profile of this novel CgAM.

PMID- 22865070
TI  - High-level production of the industrial product lycopene by the photosynthetic
      bacterium Rhodospirillum rubrum.
AB  - The biosynthesis of the major carotenoid spirilloxanthin by the purple nonsulfur
      bacterium Rhodospirillum rubrum is thought to occur via a linear pathway
      proceeding through phytoene and, later, lycopene as intermediates. This
      assumption is based solely on early chemical evidence (B. H. Davies, Biochem. J.
      116:93-99, 1970). In most purple bacteria, the desaturation of phytoene,
      catalyzed by the enzyme phytoene desaturase (CrtI), leads to neurosporene,
      involving only three dehydrogenation steps and not four as in the case of
      lycopene. We show here that the chromosomal insertion of a kanamycin resistance
      cassette into the crtC-crtD region of the partial carotenoid gene cluster, whose
      gene products are responsible for the downstream processing of lycopene, leads to
      the accumulation of the latter as the major carotenoid. We provide spectroscopic
      and biochemical evidence that in vivo, lycopene is incorporated into the light
      harvesting complex 1 as efficiently as the methoxylated carotenoids
      spirilloxanthin (in the wild type) and 3,4,3',4'-tetrahydrospirilloxanthin (in a
      crtD mutant), both under semiaerobic, chemoheterotrophic, and photosynthetic,
      anaerobic conditions. Quantitative growth experiments conducted in dark,
      semiaerobic conditions, using a growth medium for high cell density and high
      intracellular membrane levels, which are suitable for the conventional industrial
      production in the absence of light, yielded lycopene at up to 2 mg/g (dry weight)
      of cells or up to 15 mg/liter of culture. These values are comparable to those of
      many previously described Escherichia coli strains engineered for lycopene
      production. This study provides the first genetic proof that the R. rubrum CrtI
      produces lycopene exclusively as an end product.

PMID- 22865071
TI  - Improvement of crystal solubility and increasing toxicity against Caenorhabditis
      elegans by asparagine substitution in block 3 of Bacillus thuringiensis crystal
      protein Cry5Ba.
AB  - The crystal proteins from Bacillus thuringiensis are widely used for their
      specific toxicity against insects and nematodes. The highly conserved sequence
      blocks play an important role in Cry protein stability and flexibility, the basis
      of toxicity. The block 3 in Cry5Ba subfamily has a shorter sequence (only 12
      residues) and more asparagine residues than that of others which harbor about 48
      residues but only one asparagine. Based on the theoretical structure model of
      Cry5Ba, all three asparagines in block 3 are closely located in the interface of
      putative three domains, implying their probable importance in structure and
      function. In this study, all three asparagines in Cry5Ba2 block 3 were
      individually substituted with alanine by site-directed mutagenesis. The wild-type
      and mutant proteins were overexpressed and crystallized in acrystalliferous B.
      thuringiensis strain BMB171. However, the crystals formed in one of the mutants,
      designated N586A, abnormally disappeared and dissolved into the culture
      supernatant once the sporulation cells lysed, whereas the Cry5Ba crystal and the
      other mutant crystals were stable. The mutant N586A crystal, isolated from
      sporulation cells by the ultrasonic process, was found to be easily dissolved at
      wide range of pH value (5.0 to 10.0). Moreover, the toxicity assays showed that
      the mutant N586A exhibited nearly 9-fold-higher activity against nematodes and
      damaged the host's intestine more efficiently than the native Cry5Ba2. These data
      support the presumption that the amide residue Asn586 at the interface of domains
      might adversely affect the protein flexibility, solubility and resultant toxicity
      of Cry5Ba.

PMID- 22865072
TI  - Characterization of a novel subgroup of extracellular medium-chain-length
      polyhydroxyalkanoate depolymerases from actinobacteria.
AB  - Nineteen medium-chain-length (mcl) poly(3-hydroxyalkanoate) (PHA)-degrading
      microorganisms were isolated from natural sources. From them, seven Gram-positive
      and three Gram-negative bacteria were identified. The ability of these
      microorganisms to hydrolyze other biodegradable plastics, such as short-chain
      length (scl) PHA, poly(epsilon-caprolactone) (PCL), poly(ethylene succinate)
      (PES), and poly(l-lactide) (PLA), has been studied. On the basis of the great
      ability to degrade different polyesters, Streptomyces roseolus SL3 was selected,
      and its extracellular depolymerase was biochemically characterized. The enzyme
      consisted of one polypeptide chain of 28 kDa with a pI value of 5.2. Its maximum
      activity was observed at pH 9.5 with chromogenic substrates. The purified enzyme
      hydrolyzed mcl PHA and PCL but not scl PHA, PES, and PLA. Moreover, the mcl PHA
      depolymerase can hydrolyze various substrates for esterases, such as tributyrin
      and p-nitrophenyl (pNP)-alkanoates, with its maximum activity being measured with
      pNP-octanoate. Interestingly, when poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate
      [11%]) was used as the substrate, the main hydrolysis product was the monomer (R)
      3-hydroxyoctanoate. In addition, the genes of several Actinobacteria strains,
      including S. roseolus SL3, were identified on the basis of the peptide de novo
      sequencing of the Streptomyces venezuelae SO1 mcl PHA depolymerase by tandem mass
      spectrometry. These enzymes did not show significant similarity to mcl PHA
      depolymerases characterized previously. Our results suggest that these distinct
      enzymes might represent a new subgroup of mcl PHA depolymerases.

PMID- 22865073
TI  - Identification and regulation of fusA, the polyketide synthase gene responsible
      for fusarin production in Fusarium fujikuroi.
AB  - Fusarins are a class of mycotoxins of the polyketide family produced by different
      Fusarium species, including the gibberellin-producing fungus Fusarium fujikuroi.
      Based on sequence comparisons between polyketide synthase (PKS) enzymes for
      fusarin production in other Fusarium strains, we have identified the F. fujikuroi
      orthologue, called fusA. The participation of fusA in fusarin biosynthesis was
      demonstrated by targeted mutagenesis. Fusarin production is transiently
      stimulated by nitrogen availability in this fungus, a regulation paralleled by
      the fusA mRNA levels in the cell. Illumination of the cultures results in a
      reduction of the fusarin content, an effect partially explained by a high
      sensitivity of these compounds to light. Mutants of the fusA gene exhibit no
      external phenotypic alterations, including morphology and conidiation, except for
      a lack of the characteristic yellow and/or orange pigmentation of fusarins.
      Moreover, the fusA mutants are less efficient than the wild type at degrading
      cellophane on agar cultures, a trait associated with pathogenesis functions in
      Fusarium oxysporum. The fusA mutants, however, are not affected in their
      capacities to grow on plant tissues.

PMID- 22865074
TI  - Minimum requirements of flagellation and motility for infection of Agrobacterium
      sp. strain H13-3 by flagellotropic bacteriophage 7-7-1.
AB  - The flagellotropic phage 7-7-1 specifically adsorbs to Agrobacterium sp. strain
      H13-3 (formerly Rhizobium lupini H13-3) flagella for efficient host infection.
      The Agrobacterium sp. H13-3 flagellum is complex and consists of three flagellin
      proteins: the primary flagellin FlaA, which is essential for motility, and the
      secondary flagellins FlaB and FlaD, which have minor functions in motility. Using
      quantitative infectivity assays, we showed that absence of FlaD had no effect on
      phage infection, while absence of FlaB resulted in a 2.5-fold increase in
      infectivity. A flaA deletion strain, which produces straight and severely
      truncated flagella, experienced a significantly reduced infectivity, similar to
      that of a flaB flaD strain, which produces a low number of straight flagella. A
      strain lacking all three flagellin genes is phage resistant. In addition to
      flagellation, flagellar rotation is required for infection. A strain that is
      nonmotile due to an in-frame deletion in the gene encoding the motor component
      MotA is resistant to phage infection. We also generated two strains with point
      mutations in the motA gene resulting in replacement of the conserved charged
      residue Glu98, which is important for modulation of rotary speed. A change to the
      neutral Gln caused the flagellar motor to rotate at a constant high speed,
      allowing a 2.2-fold-enhanced infectivity. A change to the positively charged Lys
      caused a jiggly motility phenotype with very slow flagellar rotation, which
      significantly reduced the efficiency of infection. In conclusion, flagellar
      number and length, as well as speed of flagellar rotation, are important
      determinants for infection by phage 7-7-1.

PMID- 22865075
TI  - Protection of wood from microorganisms by laccase-catalyzed iodination.
AB  - In the present work, Norway spruce wood (Picea abies L.) was reacted with a
      commercial Trametes versicolor laccase in the presence of potassium iodide salt
      or the phenolic compounds thymol and isoeugenol to impart an antimicrobial
      property to the wood surface. In order to assess the efficacy of the wood
      treatment, a leaching of the iodinated and polymerized wood and two biotests
      including bacteria, a yeast, blue stain fungi, and wood decay fungi were
      performed. After laccase-catalyzed oxidation of the phenols, the antimicrobial
      effect was significantly reduced. In contrast, the enzymatic oxidation of iodide
      (I(-)) to iodine (I(2)) in the presence of wood led to an enhanced resistance of
      the wood surface against all microorganisms, even after exposure to leaching. The
      efficiency of the enzymatic wood iodination was comparable to that of a chemical
      wood preservative, VP 7/260a. The modification of the lignocellulose by the
      laccase-catalyzed iodination was assessed by the Fourier transform infrared
      spectroscopy-attenuated total reflectance (FTIR-ATR) technique. The intensities
      of the selected lignin-associated bands and carbohydrate reference bands were
      analyzed, and the results indicated a structural change in the lignin matrix. The
      results suggest that the laccase-catalyzed iodination of the wood surface
      presents an efficient and ecofriendly method for wood protection.

PMID- 22865076
TI  - Insight into the evolution of magnetotaxis in Magnetospirillum spp., based on mam
      gene phylogeny.
AB  - Vibrioid- to helical-shaped magnetotactic bacteria phylogenetically related to
      the genus Magnetospirillum were isolated in axenic cultures from a number of
      freshwater and brackish environments located in the southwestern United States.
      Based on 16S rRNA gene sequences, most of the new isolates represent new
      Magnetospirillum species or new strains of known Magnetospirillum species, while
      one isolate appears to represent a new genus basal to Magnetospirillum. Partial
      sequences of conserved mam genes, genes reported to be involved in the
      magnetosome and magnetosome chain formation, and form II of the ribulose-1,5
      bisphosphate carboxylase/oxygenase gene (cbbM) were determined in the new
      isolates and compared. The cbbM gene was chosen for comparison because it is not
      involved in magnetosome synthesis; it is highly conserved and is present in all
      but possibly one of the genomes of the magnetospirilla and the new isolates.
      Phylogenies based on 16S rRNA, cbbM, and mam gene sequences were reasonably
      congruent, indicating that the genes involved in magnetotaxis were acquired by a
      common ancestor of the Magnetospirillum clade. However, in one case, magnetosome
      genes might have been acquired through horizontal gene transfer. Our results also
      extend the known diversity of the Magnetospirillum group and show that they are
      widespread in freshwater environments.

PMID- 22865077
TI  - Isolation and characterization of a sex-specific lectin in a marine red alga,
      Aglaothamnion oosumiense Itono.
AB  - In red algae, spermatial binding to female trichogynes is mediated by a lectin
      carbohydrate complementary system. Aglaothamnion oosumiense is a microscopic
      filamentous red alga. The gamete recognition and binding occur at the surface of
      the hairlike trichogyne on the female carpogonium. Male spermatia are nonmotile.
      Previous studies suggested the presence of a lectin responsible for gamete
      recognition on the surface of female trychogynes. A novel N-acetyl-D
      galactosamine-specific protein was isolated from female plants of A. oosumiense
      by affinity chromatography and named AOL1. The lectin was monomeric and did not
      agglutinate horse blood or human erythrocytes. The N-terminal amino acid sequence
      of the protein was analyzed, and degenerate primers were designed. A full-length
      cDNA encoding the lectin was obtained using rapid amplification of cDNA ends-PCR
      (RACE-PCR). The cDNA was 1,095 bp in length and coded for a protein of 259 amino
      acids with a deduced molecular mass of 21.4 kDa, which agreed well with the
      protein data. PCR analysis using genomic DNA showed that both male and female
      plants have this gene. However, Northern blotting and two-dimensional
      electrophoresis showed that this protein was expressed 12 to 15 times more in
      female plants. The lectin inhibited spermatial binding to the trichogynes when
      preincubated with spermatia, suggesting its involvement in gamete binding.

PMID- 22865078
TI  - Spatial and species variations in bacterial communities associated with corals
      from the Red Sea as revealed by pyrosequencing.
AB  - Microbial associations with corals are common and are most likely symbiotic,
      although their diversity and relationships with environmental factors and host
      species remain unclear. In this study, we adopted a 16S rRNA gene tag
      pyrosequencing technique to investigate the bacterial communities associated with
      three stony Scleractinea and two soft Octocorallia corals from three locations in
      the Red Sea. Our results revealed highly diverse bacterial communities in the Red
      Sea corals, with more than 600 ribotypes detected and up to 1,000 species
      estimated from a single coral species. Altogether, 21 bacterial phyla were
      recovered from the corals, of which Gammaproteobacteria was the most dominant
      group, and Chloroflexi, Chlamydiae, and the candidate phylum WS3 were reported in
      corals for the first time. The associated bacterial communities varied greatly
      with location, where environmental conditions differed significantly. Corals from
      disturbed areas appeared to share more similar bacterial communities, but larger
      variations in community structures were observed between different coral species
      from pristine waters. Ordination methods identified salinity and depth as the
      most influential parameters affecting the abundance of Vibrio, Pseudoalteromonas,
      Serratia, Stenotrophomonas, Pseudomonas, and Achromobacter in the corals. On the
      other hand, bacteria such as Chloracidobacterium and Endozoicomonas were more
      sensitive to the coral species, suggesting that the host species type may be
      influential in the associated bacterial community, as well. The combined
      influences of the coral host and environmental factors on the associated
      microbial communities are discussed. This study represents the first comparative
      study using tag-pyrosequencing technology to investigate the bacterial
      communities in Red Sea corals.

PMID- 22865079
TI  - Effect of inorganic and organic ligands on the bioavailability of methylmercury
      as determined by using a mer-lux bioreporter.
AB  - A mer-lux bioreporter was constructed to assess the bioavailability of
      methylmercury [CH(3)Hg(II)] in Escherichia coli. The bioreporter was shown to be
      sensitive, with a detection limit of 2.5 nM CH(3)Hg(II), and was used to
      investigate the effects of chlorides, humic acids, and thiols on the
      bioavailability of CH(3)Hg(II) in E. coli. It was found that increasing the
      concentration of chlorides resulted in an increase in CH(3)Hg(II)
      bioavailability, suggesting that there was passive diffusion of the neutral
      complex (CH(3)HgCl(0)). Humic acids were found to reduce the bioavailability of
      CH(3)Hg(II) in varying degrees. Complexation with cysteine resulted in increased
      bioavailability of CH(3)Hg(II), while assays with equivalent concentrations of
      methionine and leucine had little or no effect on bioavailability. The mechanism
      of uptake of the mercurial-cysteine complexes is likely not passive diffusion but
      could result from the activities of a cysteine transport system. The
      bioavailability of CH(3)Hg(II) decreased with increasing glutathione
      concentrations.

PMID- 22865080
TI  - Ecology of Vibrio parahaemolyticus and Vibrio vulnificus in the coastal and
      estuarine waters of Louisiana, Maryland, Mississippi, and Washington (United
      States).
AB  - Vibrio parahaemolyticus and Vibrio vulnificus, which are native to estuaries
      globally, are agents of seafood-borne or wound infections, both potentially
      fatal. Like all vibrios autochthonous to coastal regions, their abundance varies
      with changes in environmental parameters. Sea surface temperature (SST), sea
      surface height (SSH), and chlorophyll have been shown to be predictors of
      zooplankton and thus factors linked to vibrio populations. The contribution of
      salinity, conductivity, turbidity, and dissolved organic carbon to the incidence
      and distribution of Vibrio spp. has also been reported. Here, a multicoastal, 21
      month study was conducted to determine relationships between environmental
      parameters and V. parahaemolyticus and V. vulnificus populations in water,
      oysters, and sediment in three coastal areas of the United States. Because
      ecologically unique sites were included in the study, it was possible to analyze
      individual parameters over wide ranges. Molecular methods were used to detect
      genes for thermolabile hemolysin (tlh), thermostable direct hemolysin (tdh), and
      tdh-related hemolysin (trh) as indicators of V. parahaemolyticus and the
      hemolysin gene vvhA for V. vulnificus. SST and suspended particulate matter were
      found to be strong predictors of total and potentially pathogenic V.
      parahaemolyticus and V. vulnificus. Other predictors included chlorophyll a,
      salinity, and dissolved organic carbon. For the ecologically unique sites
      included in the study, SST was confirmed as an effective predictor of annual
      variation in vibrio abundance, with other parameters explaining a portion of the
      variation not attributable to SST.

PMID- 22865081
TI  - Effects of UV-B radiation and periodic desiccation on the morphogenesis of the
      edible terrestrial cyanobacterium Nostoc flagelliforme.
AB  - The terrestrial cyanobacterium Nostoc flagelliforme Berk. et M. A. Curtis has
      been a popular food and herbal ingredient for hundreds of years. To meet great
      market demand and protect the local ecosystem, for decades researchers have tried
      to cultivate N. flagelliforme but have failed to get macroscopic filamentous
      thalli. In this study, single trichomes with 50 to 200 vegetative cells were
      induced from free-living cells by low light and used to investigate the
      morphogenesis of N. flagelliforme under low UV-B radiation and periodic
      desiccation. Low-fluence-rate UV-B (0.1 W m(-2)) did not inhibit trichome growth;
      however, it significantly increased the synthesis of extracellular
      polysaccharides and mycosporine-like amino acids and promoted sheath formation
      outside the trichomes. Under low UV-B radiation, single trichomes developed into
      filamentous thalli more than 1 cm long after 28 days of cultivation, most of
      which grew separately in liquid BG11 medium. With periodic desiccation treatment,
      the single trichomes formed flat or banded thalli that grew up to 2 cm long after
      3 months on solid BG11 medium. When trichomes were cultivated on solid BG11
      medium with alternate treatments of low UV-B and periodic desiccation, dark and
      scraggly filamentous thalli that grew up to about 3 cm in length after 40 days
      were obtained. In addition, the cultivation of trichomes on nitrogen-deficient
      solid BG11 medium (BG11(0)) suggested that nitrogen availability could affect the
      color and lubricity of newly developed thalli. This study provides promising
      techniques for artificial cultivation of N. flagelliforme in the future.

PMID- 22865082
TI  - Cloning and expression analysis of genes encoding lytic endopeptidases L1 and L5
      from Lysobacter sp. strain XL1.
AB  - Lytic enzymes are the group of hydrolases that break down structural polymers of
      the cell walls of various microorganisms. In this work, we determined the
      nucleotide sequences of the Lysobacter sp. strain XL1 alpA and alpB genes, which
      code for, respectively, secreted lytic endopeptidases L1 (AlpA) and L5 (AlpB). In
      silico analysis of their amino acid sequences showed these endopeptidases to be
      homologous proteins synthesized as precursors similar in structural organization:
      the mature enzyme sequence is preceded by an N-terminal signal peptide and a pro
      region. On the basis of phylogenetic analysis, endopeptidases AlpA and AlpB were
      assigned to the S1E family [clan PA(S)] of serine peptidases. Expression of the
      alpA and alpB open reading frames (ORFs) in Escherichia coli confirmed that they
      code for functionally active lytic enzymes. Each ORF was predicted to have the
      Shine-Dalgarno sequence located at a canonical distance from the start codon and
      a potential Rho-independent transcription terminator immediately after the stop
      codon. The alpA and alpB mRNAs were experimentally found to be monocistronic;
      transcription start points were determined for both mRNAs. The synthesis of the
      alpA and alpB mRNAs was shown to occur predominantly in the late logarithmic
      growth phase. The amount of alpA mRNA in cells of Lysobacter sp. strain XL1 was
      much higher, which correlates with greater production of endopeptidase L1 than of
      L5.

PMID- 22865083
TI  - Endoscopic total arytenoidectomy for bilateral abductor vocal fold paralysis: a
      new flap technique and personal experience with 50 cases.
AB  - OBJECTIVES/HYPOTHESIS: Bilateral vocal fold paralysis is a very serious
      complication of thyroid surgery, with resulting airway obstruction, aspiration,
      swallowing disturbance, and voice change. When treated with endoscopic total
      arytenoidectomy, airway obstruction may be relieved; however, there are concerns
      that voice may be seriously and irreversibly damaged and aspiration may become a
      permanent problem. STUDY DESIGN: Prospective, cohort study. METHODS: Fifty
      patients with bilateral vocal fold paralysis underwent endoscopic total
      arytenoidectomy, medially based mucosal advancement flap, and vocal fold
      lateralization with endoscopic microsuture. Pre- and postoperative evaluations
      included Voice Handicap Index (VHI-30), aerodynamic and acoustic analysis,
      subjective comparison of pre- and postoperative voice by phoniatrician, speech
      intensity measurement, breathing ability evaluation, and functional outcome
      swallowing scale. RESULTS: All VHI-30 results, all aerodynamic analysis results,
      and all acoustic results (except F0) worsened significantly after surgery (P <
      .05). Subjective comparison of pre- and postoperative voice by phoniatrician
      revealed somewhat worse voice (94%). Mean speech intensity decreased from 65 dB
      to 60 dB postoperatively (P < .05). Postoperative breathing ability was
      significantly better (90%). The pre- and postoperative functional outcome
      swallowing scales were not significantly different (P > .05). CONCLUSIONS:
      Endoscopic total arytenoidectomy is still a very successful static surgical
      option for bilateral vocal fold paralysis. It is performed without a tracheotomy,
      but may be required in some patients postoperatively. Laser is not a requirement
      for it, and it can easily be done with cold instruments. It attains comfortable
      airway with acceptable voice. Postoperatively, it does not increase aspiration
      significantly. It has good long-term results.

PMID- 22865088
TI  - [Dates].

PMID- 22865089
TI  - Automatic laser scanning ablation system for high-precision treatment of brain
      tumors.
AB  - Complete removal of malignant gliomas is important for the prognosis in
      neurosurgery treatment. Currently, the challenge is how to detect any remaining
      tumors and resect them during the operation. We have developed a laser ablation
      system with accurate tumor analysis and fluorescence guidance for high-precision
      brain tumor resection during neurosurgery. A 5-aminolevulinic acid-induced
      fluorescent protoporphyrins IX (PpIX)-based intra-operative fluorescence
      measurement and corresponding spectra analysis technique is used to identify the
      position of tumors. A galvano mirror scanning mechanism is integrated into the
      fluorescence measurement and the laser ablation devices for automatic tumor area
      scanning and corresponding laser ablation. A set of phantom experiments was
      performed to evaluate the proposed system. Results showed that the galvano
      scanning mechanism enabled both PpIX fluorescence detection and laser ablation in
      the same optical axis. In vitro experiments using porcine brain were performed to
      evaluate the effectiveness of the automatic laser scanning, fluorescence
      detection, and laser ablation system. The proposed fluorescence-guided laser
      ablation system can provide accurate analysis and high-precision treatment for
      tumor resection in neurosurgery. With further improvement, the system can be used
      in neurosurgical implementation to provide accurate, safe, and simple surgical
      diagnosis and therapy.

PMID- 22865090
TI  - Transcriptional and translational plasticity in rodent urinary bladder TRP
      channels with urinary bladder inflammation, bladder dysfunction, or postnatal
      maturation.
AB  - These studies examined the transcriptional and translational plasticity of three
      transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) with
      established neuronal and non-neuronal expression and functional roles in the
      lower urinary tract. Mechanosensor and nociceptor roles in either physiological
      or pathological lower urinary tract states have been suggested for TRPA1, TRPV1,
      and TRPV4. We have previously demonstrated the neurochemical, organizational, and
      functional plasticity in micturition reflex pathways following induction of
      urinary bladder inflammation using the antineoplastic agent, cyclophosphamide.
      More recently, we have characterized similar plasticity in micturition reflex
      pathways in a transgenic mouse model with chronic urothelial overexpression (OE)
      of nerve growth factor (NGF) and in a transgenic mouse model with deletion of
      vasoactive intestinal polypeptide (VIP). In addition, the micturition reflex
      undergoes postnatal maturation that may also reflect plasticity in urinary
      bladder TRP channel expression. Thus, we examined plasticity in urinary bladder
      TRP channel expression in diverse contexts using a combination of quantitative,
      real-time PCR and western blotting approaches. We demonstrate transcriptional and
      translational plasticity of urinary bladder TRPA1, TRPV1, and TRVP4 expression.
      Although the functional significance of urinary bladder TRP channel plasticity
      awaits further investigation, these studies demonstrate context- (inflammation,
      postnatal development, NGF-OE, VIP deletion) and tissue-dependent (urothelium +
      suburothelium, detrusor) plasticity.

PMID- 22865091
TI  - A 30-year-single-center experience in atrial myxomas: from presentation to
      treatment and prognosis.
AB  - BACKGROUND: The symptoms of myxoma are atypical, vary greatly, and may mimic
      numerous conditions. Our aim was to investigate the correlation of localization,
      size, and consistency of myxoma with its treatment and prognosis. METHODS: Over a
      span of 30 years, 74 consecutive patients (24 men, mean age 46.7 years) were
      surgically treated for echocardiography-diagnosed myxomas at our center. RESULTS:
      Left atrial myxomas were more frequent (89.19%), with the racemous form being
      predominantly left-sided and having no difference in tumor size regardless of
      localization. Three patients were asymptomatic; and those who were symptomatic,
      symptoms appeared 2 to 36 months (mean 13.60 +/- 7.52) before diagnosis.
      Nonspecific symptoms and signs were present in 91.98% of patients, whereas
      specific symptoms and signs were present in 74.32%. More often, patients with
      myxomas >5 cm in diameter were symptomatic. Embolic events occurred in 15
      patients (9 cerebral, 4 pulmonary, 2 peripheral), more frequently in right atrial
      myxomas of >5 cm diameter. All patients were surgically treated on diagnoses,
      with no intraoperative mortality or recurrences. CONCLUSIONS: Symptoms in our
      cardiac myxoma patients were more pronounced when the myxomas were left-sided,
      racemous, and over 5 cm in diameter. Even in asymptomatic patients, a high index
      of suspicion assured timely diagnosis and management.

PMID- 22865092
TI  - Complex facilitation and competition in a temperate grassland: loss of plant
      diversity and elevated CO2 have divergent and opposite effects on oak
      establishment.
AB  - Encroachment of woody vegetation into grasslands is a widespread phenomenon that
      alters plant community composition and ecosystem function. Woody encroachment is
      often the result of fire suppression, but it may also be related to changes in
      resource availability associated with global environmental change. We tested the
      relative strength of three important global change factors (CO(2) enrichment,
      nitrogen deposition, and loss of herbaceous plant diversity) on the first 3 years
      of bur oak (Quercus macrocarpa) seedling performance in a field experiment in
      central Minnesota, USA. We found that loss of plant diversity decreased initial
      oak survival but increased overall oak growth. Conversely, elevated CO(2)
      increased initial oak seedling survival and reduced overall growth, especially at
      low levels of diversity. Nitrogen deposition surprisingly had no net effect on
      survival or growth. The magnitude of these effects indicates that long-term woody
      encroachment trends may be most strongly associated with those few individuals
      that survive, but grow much larger in lower diversity patches. Further, while the
      CO(2) results and the species richness results appear to describe opposing
      trends, this is due only to the fact that the natural drivers are moving in
      opposite directions (decreasing species richness and increasing CO(2)).
      Interestingly, the mechanisms that underlie both patterns are very similar,
      increased CO(2) and increased species richness both increase herbaceous biomass
      which (1) increases belowground competition for resources and (2) increases
      facilitation of early plant survival under a more diverse plant canopy; in other
      words, both competition and facilitation help determine community composition in
      these grasslands.

PMID- 22865093
TI  - B-cell receptor pathobiology and targeting in NHL.
AB  - B-cell receptor signaling plays varied and critical roles in B-cell development,
      homeostasis and disease. The key players of the pathway and its many signaling
      modulators have been identified as well as some of the mechanisms by which the
      pathway is regulated. With the increased incidence of non-Hodgkin's lymphoma in
      recent years, there is a clear clinical need for novel agents to offer new
      options in resistant disease to potentially improve outcomes in curative
      settings. With the tremendous insight gained in the last 2 decades from basic
      science research, our understanding of the pathobiology of the B-cell receptor is
      leading to the discovery and clinical development of many new therapeutic targets
      such as Syk, Bruton's tyrosine kinase, and phosphatidylinositol 3-kinase. This
      review will emphasize contemporary and salient findings on novel agents targeting
      the B-cell receptor signaling pathway for the treatment of non-Hodgkin's
      lymphoma.

PMID- 22865094
TI  - Antimutagenic properties of Mangifera indica L. stem bark extract and evaluation
      of its effects on hepatic CYP1A1.
AB  - Mangifera indica stem bark extract (MSBE) is a Cuban natural product which has
      shown strong antioxidant properties. In this work, the antimutagenic effect of
      MSBE was tested against 10 well-known mutagens/carcinogens in the Ames test in
      the absence or presence of metabolic fraction (S9). The chemical mutagens tested
      included: cyclophosphamide, mitomycin C, bleomycin, cisplatin,
      dimethylnitrosamine (DMNA), benzo[a]pyrene (BP), 2-acetylaminofluorene (2-AAF),
      sodium azide, 1-nitropyrene (1-NP) and picrolonic acid. Protective effects of the
      extract were also evaluated by comparing the efficiency of S9 fraction obtained
      from rats treated during 28 days with oral doses of MSBE (50-500 mg/kg) with that
      obtained from rats treated with vehicle (control) to activate bleomycin and
      cyclophosphamide in the Ames test. MSBE concentrations between 50 and 500
      MUg/plate significantly reduced the mutagenicity mediated by all the chemicals
      tested with the exception of sodium azide. Higher mutagenicity was found when
      bleomycin and cyclophosphamide (CP) were activated by control S9 than by MSBE S9.
      In addition, inhibition of CYP1A1 microsomal activity was observed in the
      presence of MSBE (10-20 MUg/ml). We can conclude that besides its potent
      antioxidant activity previously reported, MSBE may also exert a chemoprotective
      effect due to its capacity to inhibit CYP activity.

PMID- 22865095
TI  - Analytical approach to characterize the intratumoral pharmacokinetics and
      pharmacodynamics of gefitinib in a glioblastoma model.
AB  - Heterogeneity in brain tumors can result in variable drug distribution and
      possibly drug response; however, there are no readily accessible means to obtain
      regional pharmacokinetic (PK)/pharmacodynamic (PD) information in preclinical
      tumor models that typically rely on average drug concentration measurements. On
      the basis of a novel serial brain tumor sectioning protocol, sensitive and robust
      methods were developed to characterize the intratumoral PK [liquid chromatography
      with tandem mass spectrometry detection (LC/MS/MS)] and PD (phosphorylated
      extracellular-signal-regulated kinase, antibody-based detection) of gefitinib in
      small amounts of glioblastoma tumor samples obtained from mice bearing
      intracerebral tumors administered 150 mg/kg of gefitinib. LC/MS/MS method was
      accurate (+/-15%) and precise (coefficient of variation <=15%). For PD analysis,
      two antibody-based assay systems [enzyme-linked immunosorbent assay and meso
      scale discovery (MSD)] were compared and the more sensitive method (MSD) was
      selected. Gefitinib concentrations showed up to 2.4 +/- 0.7-fold intratumoral
      variability in PK and 1.5 +/- 0.20-fold variability in PD. The methods are
      sufficiently accessible and could be applied to other anticancer drugs and tumor
      models to obtain greater resolution of intratumoral PKs and PDs.

PMID- 22865096
TI  - Individual differences in the development of self-regulation during pre
      adolescence: connections to context and adjustment.
AB  - Difficulties with self-regulation are implicated in the development of emotional
      and behavioral problems during adolescence. Although children's ability to
      regulate their behaviors continues to improve throughout childhood and
      adolescence, it remains unclear how contextual risk factors might influence this
      development during the transition to adolescence, or how variation in the
      development of self-regulation predicts adjustment. Using a community sample of
      214 8-12 year-olds (T1 M = 9.5, SD = 1.01), we examined growth trajectories of
      effortful control and impulsivity over three years and tested predictors and
      outcomes of these trajectories. Although predictors of initial levels of self
      regulation were largely equivalent for both effortful control and impulsivity,
      contextual risk factors were related to variations in the development of
      impulsivity but not effortful control. However, increases in effortful control,
      but not impulsivity, were associated with level and rate of change in adjustment
      problems and positive adjustment, suggesting that different dimensions of self
      regulation have different antecedents and outcomes in pre-adolescence and
      adolescence.

PMID- 22865099
TI  - Interorganizational relationships among family support organizations and child
      mental health agencies.
AB  - This study examined: (1) qualitative aspects of close working relationships
      between family support organizations and child mental health agencies, including
      effective and ineffective characteristics of the relationship and aspects that
      they would change, and (2) the impact of the working relationship upon the family
      support organization. Semi-structured interviews were conducted with 40 directors
      of family support organizations characterized as having a close working
      relationship with a child mental health agency. Three main themes emerged
      regarding the quality of the working relationship: (a) interactional factors,
      including shared trust, communication, collaboration and service coordination;
      (b) aspects of the inner context of the family support organization, mental
      health agency, or both, including alignment of goals and values and perceptions
      of mental health services; and (c) outer contextual factors external to the
      organizations, such as financial and county regulations. Responses to the
      perceived impact of the relationship was divided into two themes: positive
      impacts (e.g. gained respect, influence and visibility), and negative impacts
      (e.g. lack of trust). This study lays the foundation for future research to
      better understand the mechanisms underlying interorganizational relationships in
      communities among different types of providers to create a more seamless
      continuum of services for families of children with mental health conditions.

PMID- 22865098
TI  - Targeting the PI3K/Akt/mTOR pathway for breast cancer therapy.
AB  - Recent advances in genetics and genomics have revealed new pathways that are
      aberrantly activated in many breast cancers. Chief among these genetic changes
      are somatic mutations and/or gains and losses of key genes within the
      phosphoinositide 3-kinase (PI3K) pathway. Since breast cancer cell growth and
      progression is often dependent upon activation of the PI3K pathway, there has
      been intense research interest in finding therapeutic agents that can selectively
      inhibit one or more constituents of this signaling cascade. Here we review key
      molecules involved with aberrant PI3K pathway activation in breast cancers and
      current efforts to target these components for therapeutic gain.

PMID- 22865100
TI  - Influence of symptom expectancies on stair-climbing performance in chronic
      fatigue syndrome: effect of study context.
AB  - BACKGROUND: In patients with chronic fatigue syndrome (CFS), performance of
      physical activities may be affected by an anticipated increase in symptoms after
      these activities. Nijs et al. previously studied the influence of symptom
      expectancies and related psychological processes on the performance of an
      isolated physical activity [Nijs J, Meeus M, Heins M, Knoop H, Moorkens G,
      Bleijenberg G. Kinesiophobia, catastrophizing and anticipated symptoms before
      stair climbing in chronic fatigue syndrome: an experimental study. Disabil
      Rehabil 2012. doi: 10.3109/09638288.2011.641661 .]. PURPOSE: We aimed to validate
      the previous findings in a larger group of patients in a different setting. We
      also extended the possible underlying psychological processes studied. METHOD: In
      49 CFS patients, we measured performance (duration and increase in heart rate)
      during self-paced climbing and descending of two floors of stairs. Before this
      task, patients rated experienced fatigue and anticipated fatigue after stair
      climbing. In addition, kinesiophobia, catastrophising and focusing on bodily
      symptoms were measured. Using correlational and regression analyses, we tested
      whether performance during stair climbing could be explained by experienced and
      anticipated fatigue and psychological factors. RESULTS: Longer duration of stair
      climbing correlated with higher anticipated fatigue, independently of sex, age,
      body mass index and fatigue before stair climbing. Focusing on bodily symptoms
      and fatigue-related catastrophising were related to anticipated fatigue.
      CONCLUSION: Symptom expectations affect the performance of physical activity in
      CFS patients, possibly through focusing on bodily symptoms and catastrophising.
      These findings partially contradict the findings of the previous study, which
      stresses the importance of study context in conducting this type of experiments
      (i.e., patient characteristics, instructions).

PMID- 22865101
TI  - Is biology destiny? Birth weight and differential parental treatment.
AB  - Time diaries of sibling pairs from the PSID-CDS are used to determine whether
      maternal time investments compensate for or reinforce birth-weight differences
      among children. The findings demonstrate that the direction and degree of
      differential treatment vary by mother's education. Less-educated mothers devote
      more total time and more educationally oriented time to heavier-birth-weight
      children, whereas better-educated mothers devote more total and more
      educationally oriented time to lower-birth-weight children. The compensating
      effects observed among highly educated mothers are substantially larger than the
      reinforcing effects among the least-educated mothers. The findings show that
      families redistribute resources in ways that both compensate for and exacerbate
      early-life disadvantages.

PMID- 22865102
TI  - Analyzing small samples with high efficiency: capillary batch injection-capillary
      electrophoresis-mass spectrometry.
AB  - We present an experimental approach to conducting fast capillary electrophoresis
      mass spectrometry (CE-MS) measurements of very small samples in the nanoliter
      range. This is achieved by injecting sample very efficiently into a CE-MS system.
      Injection efficiency represents the ratio of injected sample to the amount of
      sample needed for carrying out the injection process (v/v). In order to increase
      this injection efficiency from typical values of 10(-3) to 10(-7), the concept of
      capillary batch injection is used to build an automated, small-footprint
      injection device for CE-MS. This device is capable of running true multi-sample
      measurement series, using minimal sample volumes and delivering an injection
      efficiency of up to 100 %. It is compatible with both aqueous and non-aqueous
      background electrolytes. As an additional benefit, CE-MS separations of a
      catecholamine model system in capillaries of 15 cm length under conditions of
      high electric field strength could be accomplished in 20 s with high separation
      efficiency. This report details design and specifications of the injection device
      and shows optimal parameter choices for injections with both high injection
      efficiency and high separation efficiency. Furthermore, a procedure is presented
      to coat the tip of a fused silica capillary with a silicone elastomer which acts
      as a seal between two capillaries.

PMID- 22865103
TI  - Palladium nanoparticle-decorated iron nanotubes hosted in a polycarbonate porous
      membrane: development, characterization, and performance as electrocatalysts of
      ascorbic acid.
AB  - One-dimensional iron metallic nanotubes were prepared by electroless deposition
      within the pores of polycarbonate (PC) membranes. The longitudinal nucleation of
      the nanotubes along the pore walls was achieved by mounting the PC membrane
      between two halves of a U-shaped reaction tube. Palladium nanoparticles were post
      deposited on the inner wall of the nanotubes. The composition, morphology, and
      structure of the Pd/Fe nanotubes were characterized by transmission electron
      microscopy, scanning electron microscopy, and inductively coupled plasma-atomic
      emission spectroscopy. A glassy carbon (GC) electrode modified with the free
      Pd/Fe bimetallic nanotubes (isolated after the dissolution of the host membranes)
      showed small improvement on the overpotential oxidation of ascorbic acid in
      comparison to the bare GC electrode. Alternatively, the Pd/Fe-polycarbonate
      membrane was covered with a sputtered gold thin layer of 10 nm from one side and
      mounted in a homemade electrochemical cell acting as the working electrode. The
      potential use of these functional membranes as catalytic surfaces for the
      electrochemical monitoring of ascorbic acid was investigated by cyclic
      voltammetry and amperometry. In the presence of a phosphate buffer solution, pH
      7, Pd/Fe-polycarbonate membranes showed excellent electrocatalytic properties
      toward the oxidation of ascorbic acid even at potentials as low as 0 mV versus a
      Ag/AgCl reference electrode. In addition to the substantial lower overpotential,
      these electrodes offered selectivity over acetaminophen and uric acid, and a
      prolonged working stability without the need for maintenance. The electrodes were
      kept dry between different working days and retained their original activity for
      more than 1 week. Pd-polycarbonate and Fe-polycarbonate membranes were also
      developed for comparison purposes.

PMID- 22865104
TI  - The effects of botulinum toxin injections into the cricopharyngeus muscle of
      patients with cricopharyngeus dysfunction associated with pharyngo-laryngeal
      weakness.
AB  - This prospective, open study was carried out in order to assess changes in the
      swallowing and dietary status after injection of Botulinum toxin A (BoNT-A) into
      the upper esophageal sphincter (UES) in a series of patients with cricopharyngeus
      (CP) muscle dysfunction associated with pharyngo-laryngeal weakness during at
      least 1 year follow-up after treatment. Patients who had a cricopharyngeus (CP)
      muscle dysfunction associated with pharyngo-laryngeal weakness and who were at
      risk for aspiration were included in the study. The upper border of the cricoid
      cartilage was identified and the CP muscle localized using a standard
      electromyogram (EMG). The dose of BoNT-A was determined depending on the results
      of EMG performed just before the injection. Outcomes were assessed by the
      penetration-aspiration scale (PAS), the level of residue in the pyriform sinus
      and the National Institute of Health-Swallow Safety Scale (NIH-SSS) on a video
      fluoroscopic swallowing (VFSS) assessment, the patient's subjective impressions
      of their ability to swallow by the Deglutition Handicap Index (DHI), and changes
      in dietary status by the Functional Oral Intake Scale. Eleven patients underwent
      the complete assessment of swallowing function at 1, 3, 6, and 12 months. After
      the first set of treatment, seven patients had a good response and four did not
      respond. A significant decrease in the PAS score (p = 0.03), the amount of
      residue (p = 0.04) and the NIH-SSS score (p = 0.03) was observed 3 months after
      the injection in comparison with the first VFSS before the treatment. A relapse
      of dysphagia occurred in 3 out of the 11 treated patients; at 3 and 4 months for
      2 patients with a Wallenberg syndrome, and at 11 months for a patient with
      cranial nerve paralysis after a surgery for a glomus tumor. Two of them underwent
      a second injection. One patient had a good response and remained stable for at
      least 1 year. The second did not respond either to the second injection or to a
      myotomy of the cricopharyngeal muscle. The third one is waiting for further
      surgery (myotomy). Therefore, at the end of the study and after a follow-up of at
      least 12 months, 5 patients out of the 11 enrolled had a good result.
      Percutaneous injection of BoNT-A into the UES can be a useful solution to improve
      cricopharyngeal dysfunction, despite the underlying pharyngo-laryngeal weakness.

PMID- 22865105
TI  - Head and neck squamous carcinomas with exophytic and endophytic type of growth
      have the same prognosis after surgery and adjuvant radiotherapy.
AB  - Head and neck squamous cell carcinomas (HNSCC) are characterized by exophytic or
      endophytic growth. We hypothesized that the growth pattern predicts outcome and
      associates with distinct clinical and immunological profiles. Tumors obtained
      from 60 HNSCC patients treated with surgery and adjuvant radiotherapy were
      identified as exophytic or endophytic. Recurrence-free survival (RFS) at 42
      months was determined. In a subsets of 30 patients (22 exophytic and 8
      endophytic) tumor stroma and parenchyma were evaluated for infiltrating CD4(+)
      and CD8(+) T, dendritic, myeloid and FOXP3(+) regulatory T cells (Treg) and
      expression of immunosuppressive cytokines by immunohistochemistry. The
      localization and frequency of positive cells were determined microscopically and
      analyzed by hierarchical clustering to distinguish exophytic versus endophytic
      tumors. 34/60 patients had exophytic and 26/60 endophytic tumors. No differences
      in clinicopathologic data, disease progression or RFS were seen between the two
      cohorts. Infiltrates of CD3(+)CD8(+) T cells were larger in endophytic than
      exophytic tumors, while FOXP3(+) Treg, TGF-beta(+), IL-10(+), Arg-1(+), CD11b(+)
      cells were equally prominent in both. FOXP3(+) Treg accumulated in endophytic
      tumor nests, while the exophytic tumor stroma was enriched in IL-10(+) cells
      (both at p < 0.05). Hierarchical clustering based on immunophenotyping failed to
      identify different clusters in these two tumor types. However, CD68(+)
      macrophages and FOXP3(+) Treg showed a distinct distribution. The HNSCC growth
      pattern did not predict RFS. Although higher numbers and differences in
      localization of immunosuppressive cells in endophytic versus exophytic tumors
      were observed, no significant relationship was established between the growth
      pattern and the immune profile of infiltrating lymphocytes.

PMID- 22865106
TI  - Surgical site infection in clean-contaminated head and neck cancer surgery: risk
      factors and prognosis.
AB  - Since new treatment strategies, such as chemoradiotherapy, have been introduced
      for head and neck cancer, a higher number of unknown factors may be involved in
      surgical site infection in clean-contaminated head and neck cancer surgery. The
      aim of the present study was to clarify the risk factors of surgical site
      infection in clean-contaminated surgery for head and neck cancer and the
      prognosis of patients with surgical site infection. Participants were 277
      consecutive patients with head and neck cancer who underwent clean-contaminated
      surgery for primary lesions at the Aichi Cancer Center over a 60-month period. A
      total of 22 putative risk factors were recorded in each patient and statistically
      analyzed to elucidate surgical site infection related factors. Surgical site
      infection was observed in 92 (32.1 %) of 277 cases. Univariate analysis indicated
      that alcohol consumption, T classification, neck dissection, reconstructive
      procedure, and chemoradiotherapy were significantly associated with surgical site
      infection. Multiple logistic regression analysis identified two independent risk
      factors for surgical site infection: reconstructive surgery (p = 0.04; odds ratio
      (OR) 1.77) and chemoradiotherapy (p = 0.01; OR 1.93). In spite of surgical site
      infection, the five-year overall survival rate of patients with surgical site
      infection was not significantly different from those without surgical site
      infection. Although surgical site infection did not impact the overall survival
      of patients with surgical procedures, head and neck surgeons should pay attention
      to patients with previous chemoradiotherapy as well as to those with a high risk
      of surgical site infection requiring reconstructive surgery.

PMID- 22865107
TI  - Should we exclude inadequately reported studies from qualitative systematic
      reviews? An evaluation of sensitivity analyses in two case study reviews.
AB  - The role of critical appraisal of qualitative studies in systematic reviews
      remains an ongoing cause for debate. Key to such a debate is whether quality
      assessment can or should be used to exclude studies. In our study, we extended
      the use of existing criteria to assess the quality of reporting of studies
      included in two qualitative systematic reviews. We then excluded studies deemed
      to be inadequately reported from the subsequent analysis. We tested the impact of
      these exclusions on the overall findings of the synthesis and its depth or
      thickness. Exclusion of so-called inadequately reported studies had no meaningful
      effect on the synthesis. There was a correlation between quality of reporting of
      a study and its values as a source for the final synthesis. We propose that there
      is a possible case for excluding inadequately reported studies from qualitative
      evidence synthesis.

PMID- 22865108
TI  - Cross-reactive responses to modified M158-66 peptides by CD8+ T cells that use
      noncanonical BV genes can describe unknown repertoires.
AB  - Memory T-cell repertoires are populated by clonotypes selected by an individual's
      history of antigen exposures. Our previous analysis of middle-age CD8(+)  T-cell
      memory repertoires to the influenza-derived epitope M1(58-66) , described a
      network of highly cross-reactive BV19 clonotypes responding to M1(58-66)  and at
      least one peptide with a conservative amino acid substitution at either of two
      TCR contact positions. Here, we report that some substitutions abrogate BV19
      responses and favor responses with different BV. Cross-reactive T cells using
      seven other BV families responded to 12 of 13 peptides tested. BV12 clonotypes
      define the most extensive cross-reactive network that encompasses seven peptides.
      We generated 3D networks based on the peptides recognized and BV family used and
      observed a cluster of five peptides that includes M1(58-66)  and another cluster
      of five peptides that does not include M1(58-66) . The first cluster represents
      peptides structurally similar to M1(58-66) , and the second represents peptides
      with more considerable changes in epitope recognition surface. We hypothesize
      that the second cluster represents the cross-reactive network around another
      unknown epitope or epitopes. This data supports a model of stable CD8(+)  T-cell
      memory networks that include a substantial contribution from cross-reactive T
      cells.

PMID- 22865109
TI  - Controlled immobilisation of active enzymes on the cowpea mosaic virus capsid.
AB  - Immobilisation of horseradish peroxidase (HRP) and glucose oxidase (GOX) via
      covalent attachment of modified enzyme carbohydrate to the exterior of the cowpea
      mosaic virus (CPMV) capsid gave high retention of enzymatic activity. The number
      of enzymes bound per virus was determined to be about eleven for HRP and 2-3 for
      GOX. This illustrates that relatively large biomacromolecules can be readily
      coupled to the virus surface using simple conjugation strategies. Virus
      biomacromolecule hybrids have great potential for uses in catalysis, diagnostic
      assays or biosensors.

PMID- 22865110
TI  - Quantitative trait loci associated with androgenic responsiveness in triticale
      (*Triticosecale Wittm.) anther culture.
AB  - Quantitative trait loci (QTLs) associated with androgenic responsiveness in
      triticale were analyzed using a population of 90 DH lines derived from the F1
      cross between inbred line 'Saka 3006' and cv. 'Modus', which was used in a number
      of earlier studies on molecular mapping in this crop. Using Windows QTL
      Cartographer and MapQTL 5.0, composite interval mapping (CIM) and association
      studies (Kruskal-Wallis test; K-W) for five androgenesis parameters (androgenic
      embryo induction, total regeneration and green plant regeneration ability, and
      two characteristics describing final androgenesis efficiency) were conducted. For
      the studied components of androgenic response, CIM detected in total 28 QTLs
      which were localized on 5 chromosomes from A and R genomes. Effects of all QTLs
      that were identified at 2.0 or above of the LOD score explained 5.1-21.7 % of the
      phenotypic variation. Androgenesis induction was associated with seven QTLs (LOD
      between 2.0 and 5.8) detected on chromosomes 5A, 4R, 5R and 7R, all of them
      confirmed by K-W test as regions containing the markers significantly linked to
      the studied trait. What is more, K-W test revealed additional markers on
      chromosomes: 5A, 2BL, 7B and 5R. Both total and green regeneration ability were
      controlled by genes localized on chromosome 4A. Some of the QTLs that affected
      final androgenesis efficiency were identical with those associated with
      androgenic embryo induction efficiency, suggesting that the observed correlation
      may be either due to tight linkage or to pleiotropy. Key message Five regions of
      the triticale genome were indicated as revealing significant marker/trait
      association. Markers located in these regions are potentially useful for
      triticale breeding through marker-assisted selection.

PMID- 22865112
TI  - 5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca
      sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels.
AB  - DNA methylation is an epigenetic regulatory mechanism of gene expression which
      can be associated with developmental phases and in vitro morphogenetic competence
      in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4
      dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE)
      and global DNA methylation levels by high-performance liquid chromatography mass
      spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo
      formation in both accessions tested. Treatments supplemented with 2,4-D pulse
      plus AzaC in the culture medium resulted in increased embryo formation. In AzaC
      free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation
      levels in cultures of both accessions tested during SE induction. Treatment with
      AzaC and 2,4-D-free resulted in a marked decrease in methylation for both
      accessions, ranging from 37.6 to 20.8 %. In treatment with 2,4-D and AzaC
      combined, the 85 accession showed increasing global methylation levels.
      Otherwise, the 101X458 accession, in the same treatment, showed a decrease
      between 10 and 20 days, followed by an increase after 30 days (39.5, 36.2 and
      41.6 %). These results indicate that 2,4-D pulse combined with AzaC improves SE
      induction. However, the conversion phase showed that although positively
      influencing SE induction, AzaC had a dysregulatory effect on the stage of
      autotrophic plant formation, resulting in significantly lower conversion rates.
      The results suggest that DNA methylation dramatically influences SE in Acca
      sellowiana, and global DNA methylation dynamics are related to morphogenetic
      response. KEY MESSAGE: 5-Azacytidine combined with 2,4-D increases the number of
      Acca sellowiana somatic embryos. Global DNA methylation is directly affected by
      these compounds.

PMID- 22865113
TI  - Acute-phase protein concentration and metabolic status affect the outcome of
      treatment in cows with clinical and subclinical endometritis.
AB  - The aim of this study was to investigate the role of acute-phase protein
      concentration and metabolic status in the establishment and resistance of
      clinical endometritis (CE) and subclinical endometritis (SE) in dairy cows. We
      also characterised the treatment-related changes in the concentration of acute
      phase proteins and metabolic variables in dairy cows affected by CE and SE. Cows
      of the SE and CE groups presented a significantly higher beta-hydroxybutyrate
      (BHB), haptoglobin and total sialic acid (TSA) concentrations compared with a
      healthy group of animals. A significantly lower serum calcium concentration, and
      a significantly higher serum aspartate aminotransferase activity in the CE group,
      were observed when compared with SE and healthy groups. The comparison of
      parameters before treatment indicated that cows suffering from CE or SE with
      lower concentrations of hepatic and inflammatory markers showed a better response
      to further treatment, and endometritis was not detected in the second
      examination. Moreover, decreased concentrations of BHB, acute-phase proteins and
      hepatic markers were observed after successful treatment for endometritis in CE
      and SE cows. The results obtained in this study suggest that improved liver
      function and a decrease in the acute-phase protein concentration might favour the
      resolution of endometritis after treatment.

PMID- 22865114
TI  - Evaluation of effectiveness, safety and reliability of intramuscular medetomidine
      ketamine for captive great apes.
AB  - Twenty great apes (six orangutans, eight chimpanzees and six gorillas) were
      anaesthetised prior to being transported for undergoing diagnostic and
      interventional procedures. Anaesthesia was induced with a combination of
      medetomidine and ketamine administered intramuscularly through a dart syringe.
      The onset of anaesthesia varied among apes: the mean (+/-sd) time from darting to
      recumbency was 12.13 (+/-1.9), 18.5 (+/-8.7) and 22.2 (+/-9.2) minutes in
      chimpanzees, orangutans and gorillas, respectively. The depth of anaesthesia was
      sufficient to allow safe removal of the animals from the enclosure, intravenous
      catheter placement and manipulation; however, the anaesthetic effect was short
      acting (20 (+/-7) minutes in orangutans, 16 (+/-14) in gorillas, and 10 (+/-4)
      minutes in chimpanzees, respectively) and isoflurane administration was necessary
      in the majority of the apes to prolong the duration of anaesthesia, especially
      when lengthier procedures were performed. The sedative effect of medetomidine was
      reversed at the end of each procedure with atipamezole, and recovery was smooth
      and uneventful for all animals.

PMID- 22865115
TI  - Descriptive clinical and epidemiological characteristics of influenza A H1N1 2009
      virus infections in pigs in England.
AB  - Infection of pigs with influenza A H1N1 2009 virus (A(H1N1)pdm09) was first
      detected in England in November 2009 following global spread of the virus in the
      human population. This paper describes clinical and epidemiological findings in
      the first English pig farms in which A(H1N1)pdm09 influenza virus was detected.
      These farms showed differences in disease presentation, spread and duration of
      infection. The factors likely to influence these features are described and
      relate to whether pigs were housed or outdoors, the age of the pigs, inter
      current disease and the management system of the unit. Infection could be mild or
      clinically inapparent in breeding pigs with more typical respiratory disease
      being identified later in their progeny. Mortality was low where disease was
      uncomplicated by environmental stresses or concurrent infections. Where deaths
      occurred in pigs infected with A(H1N1)pdm09 influenza, they were mainly due to
      other infections, including streptococcal disease due to Streptococcus suis
      infection. This paper demonstrates the ease with which A(H1N1)pdm09 virus was
      transmitted horizontally and maintained in a pig population.

PMID- 22865116
TI  - Mycobacterium malmoense as an extrapulmonary pathogen of cats.

PMID- 22865117
TI  - Description and evaluation of a right flank, mini-laparotomy approach to canine
      ovariohysterectomy.
AB  - Surgical ovariohysterectomy (OVH) using a right flank approach was performed in
      114 bitches as part of the Animal Birth Control (ABC) Programme at Help in
      Suffering, Jaipur, India. Incision length, duration of surgery and postoperative
      pain scores were recorded for each animal. The mean weight of the bitches was
      13.7 kg, and the mean body condition score was 4.5 on a 1-9 scale. Mean surgical
      incision length and time were 22 mm and 11 minutes 4 seconds, respectively. It
      was seen that 86.1 per cent of bitches required no additional postoperative
      analgesia. These findings compare favourably with other techniques for OVH,
      including laparoscopic techniques. The surgical approach described may be an
      alternative for canine OVH, particularly in a shelter setting.

PMID- 22865118
TI  - Purine anti-metabolite attenuates nuclear factor kappaB and related pro
      inflammatory cytokines in experimental vasospasm.
AB  - BACKGROUND: Increased nuclear factor kappaB (NF-kappaB) bioexpression, as well as
      TNF-alpha, IL-1beta and IL-6 levels, were observed after aneurysmal subarachnoid
      hemorrhage (SAH). It is of interest to investigate the effect of 6-mercaptopurine
      (6-mp) on cytokines/NF-kappaB in this SAH model. MATERIALS AND METHODS: A rodent
      double-hemorrhage SAH model was employed. Serum and cerebrospinal fluid (CSF)
      samples were collected to examine IL-1, IL-6 and TNF-alpha levels. NF-kappaB
      subunit p65 and its inhibitor of nuclear factor kappaB (IkappaB) were examined
      (by Western blot). TNF-alpha was used to induce the phosphorylation of IkappaB in
      the presence or absence of 6-mp. RESULTS: Nuclear NF-kappaB subunit p65/IkappaB
      kinase in the basilar artery was over-expressed, and cytokines was notably
      increased in the SAH groups, compared with the controls (P < 0.01). In the 6-mp
      SAH group, obvious reduction was observed in NF-kappaB subunit p65 (nuclei) (P <
      0.01). Treatment with 6-mp significantly reduced IL-1beta and TNF-alpha levels to
      those of the healthy control. 6-Mercaptopurine also significantly increased the
      level of IkappaB in the TNF-alpha-stimulated SAH rats. CONCLUSIONS: Through
      inhibiting IkappaB bioexpression, 6-mp decreases NF-kappaB-related IL-1beta, IL
      6, and TNF-alpha in the presence of SAH. The study suggests 6-mp exerts vascular
      anti-inflammatory properties through inhibiting IkappaB kinase and subsequently
      blocks bio-activation of NF-kappaB and related cytokines, which may contribute to
      its antivasospastic effect in animals subjected to SAH.

PMID- 22865119
TI  - The second short-term warm ischemia after vascular anastomosis did not affect
      early renal function recovery in renal transplantation: a case report.
AB  - Ischemic postconditioning was defined as rapid intermittent interruptions of
      blood flow in the early phase of reperfusion, which has been found to be
      protective against renal ischemia-reperfusion injury (IRI) in animal models but
      not in clinical trials.We describe a case that the allograft renal vein was
      twisted because of the surgeon's mistake, which caused the warm ischemia of
      allograft after reperfusion. The allograft restored blood flow without second
      reperfusion and cold preservation after 9 min of warm ischemia. The patient was
      followed up for 3 months and the allograft worked well without complications.

PMID- 22865120
TI  - Mechanisms and impacts of chromosomal translocations in cancers.
AB  - Chromosomal aberrations have been associated with cancer development since their
      discovery more than a hundred years ago. Chromosomal translocations, a type of
      particular structural changes involving heterologous chromosomes, have made a
      critical impact on diagnosis, prognosis and treatment of cancers. For example,
      the discovery of translocation between chromosomes 9 and 22 and the subsequent
      success of targeting the fusion product BCR-ABL transformed the therapy for
      chronic myelogenous leukemia. In the past few decades, tremendous progress has
      been achieved towards elucidating the mechanism causing chromosomal
      translocations. This review focuses on the basic mechanisms underlying the
      generation of chromosomal translocations. In particular, the contribution of
      frequency of DNA double strand breaks and spatial proximity of translocating loci
      is discussed.

PMID- 22865121
TI  - Laccase production by free and immobilized mycelia of Peniophora cinerea and
      Trametes versicolor: a comparative study.
AB  - The production of laccase by immobilized mycelia of Peniophora cinerea and
      Trametes versicolor was studied. In an initial stage, experimental assays were
      performed in Erlenmeyer flasks using free and immobilized mycelium, and the
      performance of the fungal strains to produce the enzyme was compared. Both fungi
      adhered into the support material (a synthetic fiber), growing not only on the
      surface but also in the interspaces of the fibers. Immobilization of P. cinerea
      provided a 35-fold increase in laccase production when compared to the production
      obtained by using free mycelium. On the other hand, immobilization of T.
      versicolor caused a decrease in laccase activity. A comparison between the
      strains revealed that immobilized P. cinerea (3,500 U/L) surpassed the enzyme
      production by free T. versicolor (800 U/L). When the conditions that gave the
      best laccase production to each fungus were employed in a stirred tank
      bioreactor, very low laccase production was observed for both the cases,
      suggesting that shear stress and mycelia damage caused by the agitation impellers
      negatively affected the enzyme production.

PMID- 22865122
TI  - Low-level laser therapy vs. pulsed electromagnetic field on neonatal rat
      calvarial osteoblast-like cells.
AB  - To compare the effects of pulsed electromagnetic field (PEMF) and low-level laser
      therapy (LLLT) on osteoblast cells in a cell culture model. Fifty thousand
      neonatal rat calvarial osteoblast-like cells per milliliter were seeded and 0.06
      mT PEMF, 0.2 mT PEMF, and LLLT at 808 nm were applied for 24 and 96 h on the
      cells. To evaluate cellular proliferation and differentiation, specimens were
      examined for DNA synthesis, alkaline phosphatase (ALP) activity, cell numbers,
      and viability of the cells. Morphological appearances of the cells were observed
      using scanning electron microcopy after 24 and 96 h of incubation. At 24 and 96
      h, the control group had a higher cell proliferation than 0.06 and 0.2 mT PEMF
      groups (p=0.001). At 96 h, 0.2 mT PEMF group had higher cell proliferation rate
      than 0.06 mT PEMF and LLLT groups (p=0.001). The cell count and cell viability in
      0.2 mT PEMF group were higher than the 0.06-mT PEMF and LLLT groups, although
      these differences were not statistically significant at 96 h (p>0.05). At 24 and
      96 h, cell viability in the control group was higher than the test groups.
      Alkaline phosphatase levels of the groups were comparable in both time intervals
      (p>0.05). 0.2 mT PEMF application on osteoblast-like cells led to cell
      proliferation and differentiation better than 0.06 mT PEMF and LLLT at 808 nm,
      although a remarkable effect of both PEMF and LLLT could not be detected. The ALP
      activity of 0.2 and 0.06 mT PEMF and LLLT were comparable.

PMID- 22865123
TI  - Modification and testing of a pneumatic dispensing device for controlled delivery
      of injectable materials.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold (VF) injections of viscous materials are
      typically performed using hand-operated syringes or injection guns; however,
      these methods can be imprecise due to accumulation of pressure, effort-related
      tremor, and poor feedback regarding injection volume and rate. STUDY DESIGN:
      Apparatus development with laboratory bench-top and animal model testing.
      METHODS: A foot pedal-triggered device for dispensing viscous materials was
      modified by adding a linear transducer and display for monitoring dispensed
      volume. In bench tests, bovine VFs were injected with fluids/materials of
      different viscosities (saline, glycerol, hydrogel, and liposuctioned fat) through
      narrow-bore needles using a range of driving pressures and air pulse durations.
      The device was further evaluated in >50 in vivo VF injection experiments.
      RESULTS: Device function was repeatable, with high correlations (typically R(2) >
      0.98) between the readout and direct measures of volume, even for small volumes
      (<5 MUL/pulse). Foot pedal control enabled surgeons to make steady, accurate
      injections into ferret and dog VFs during phonosurgery, and, because the
      dispenser released all driving pressure between pulses, there were no instances
      of clog-related overinjection when the obstruction cleared. CONCLUSIONS: This VF
      injection system shows promise for development to enhance human phonosurgery by
      increasing injection control and precision.

PMID- 22865124
TI  - A reference genetic map of Muscadinia rotundifolia and identification of Ren5, a
      new major locus for resistance to grapevine powdery mildew.
AB  - Muscadinia rotundifolia, a species closely related to cultivated grapevine Vitis
      vinifera, is a major source of resistance to grapevine downy and powdery mildew,
      two major threats to cultivated traditional cultivars of V. vinifera respectively
      caused by the oomycete Plasmopara viticola and the ascomycete Erisyphe necator.
      The aim of the present work was to develop a reference genetic linkage map based
      on simple sequence repeat (SSR) markers for M. rotundifolia. This map was created
      using S1 M. rotundifolia cv. Regale progeny, and covers 948 cM on 20 linkage
      groups, which corresponds to the expected chromosome number for muscadine. The
      comparison of the genetic maps of V. vinifera and M. rotundifolia revealed a high
      macrosynteny between the genomes of both species. The S1 progeny was used to
      assess the general level of resistance of M. rotundifolia to P. viticola and E.
      necator, by scoring different parameters of pathogen development. A quantitative
      trait locus (QTL) analysis allowed us to highlight a major QTL on linkage group
      14 controlling resistance to powdery mildew, which explained up to 58 % of the
      total phenotypic variance. This QTL was named 'Resistance to Erysiphe Necator 5'
      (Ren5). A microscopic evaluation E. necator mycelium development on resistant and
      susceptible genotypes of the S1 progeny showed that Ren5 exerts its action after
      the formation of the first appressorium, and acts by delaying, and then stopping,
      mycelium development.

PMID- 22865125
TI  - Genome-wide association study for oat (Avena sativa L.) beta-glucan concentration
      using germplasm of worldwide origin.
AB  - Detection of quantitative trait loci (QTL) controlling complex traits followed by
      selection has become a common approach for selection in crop plants. The QTL are
      most often identified by linkage mapping using experimental F(2), backcross,
      advanced inbred, or doubled haploid families. An alternative approach for QTL
      detection are genome-wide association studies (GWAS) that use pre-existing lines
      such as those found in breeding programs. We explored the implementation of GWAS
      in oat (Avena sativa L.) to identify QTL affecting beta-glucan concentration, a
      soluble dietary fiber with several human health benefits when consumed as a whole
      grain. A total of 431 lines of worldwide origin were tested over 2 years and
      genotyped using Diversity Array Technology (DArT) markers. A mixed model approach
      was used where both population structure fixed effects and pair-wise kinship
      random effects were included. Various mixed models that differed with respect to
      population structure and kinship were tested for their ability to control for
      false positives. As expected, given the level of population structure previously
      described in oat, population structure did not play a large role in controlling
      for false positives. Three independent markers were significantly associated with
      beta-glucan concentration. Significant marker sequences were compared with rice
      and one of the three showed sequence homology to genes localized on rice
      chromosome seven adjacent to the CslF gene family, known to have beta-glucan
      synthase function. Results indicate that GWAS in oat can be a successful option
      for QTL detection, more so with future development of higher-density markers.

PMID- 22865126
TI  - A fast expectation-maximum algorithm for fine-scale QTL mapping.
AB  - The recent technology of the single-nucleotide-polymorphism (SNP) array makes it
      possible to genotype millions of SNP markers on genome, which in turn requires to
      develop fast and efficient method for fine-scale quantitative trait loci (QTL)
      mapping. The single-marker association (SMA) is the simplest method for fine
      scale QTL mapping, but it usually shows many false-positive signals and has low
      QTL-detection power. Compared with SMA, the haplotype-based method of Meuwissen
      and Goddard who assume QTL effect to be random and estimate variance components
      (VC) with identity-by-descent (IBD) matrices that inferred from unknown historic
      population is more powerful for fine-scale QTL mapping; furthermore, their method
      also tends to show continuous QTL-detection profile to diminish many false
      positive signals. However, as we know, the variance component estimation is
      usually very time consuming and difficult to converge. Thus, an extremely fast
      EMF (Expectation-Maximization algorithm under Fixed effect model) is proposed in
      this research, which assumes a biallelic QTL and uses an expectation-maximization
      (EM) algorithm to solve model effects. The results of simulation experiments
      showed that (1) EMF was computationally much faster than VC method; (2) EMF and
      VC performed similarly in QTL detection power and parameter estimations, and both
      outperformed the paired-marker analysis and SMA. However, the power of EMF would
      be lower than that of VC if the QTL was multiallelic.

PMID- 22865127
TI  - Reduced expression of vasohibin-1 is associated with clinicopathological features
      in renal cell carcinoma.
AB  - Vasohibin-1(VASH1) has recently been isolated as a novel negative feedback
      inhibitor of angiogenesis. Several studies have demonstrated that VASH1 plays
      important roles in tumor angiogenesis but the role of this angiogenic inhibitor
      in renal cell carcinoma (RCC) has not been elucidated until now. In this study,
      we investigated the expression pattern of VASH1 and the association with
      clinicopathological features in RCC. Expression of VASH1, hypoxia-inducible
      factor-1alpha (HIF-1alpha), and microvessel density (MVD, labeled by CD34) was
      assessed by immunohistochemistry in 46 RCC specimens and 20 adjacent nontumorous
      renal tissues (ANRTs). Correlation between vasohibin-1 and HIF-1alpha, MVD, and
      clinicopathological features was then investigated. In RCC, VASH1 was expressed
      mainly in the cytoplasm and membrane of tumor cells and partly in vascular
      endothelial cells. In ANRT, it was mainly expressed in the cytoplasm and membrane
      of renal tubular epithelial cells and partly in vascular endothelial cells and
      glomerular mesangial cells. The expression level of VASH1 in RCC tissue was
      significantly lower than that in ANRT and was significantly reduced with the
      increased degree of malignancy in RCC tissues. In addition, a significantly
      negative correlation was noted between VASH1 expression and HIF-1alpha expression
      and a significantly negative correlation was noted between VASH1 expression and
      MVD in RCC. Therefore, VASH1 expression is reduced and it associates with
      clinicopathological features in RCC. Based on our findings and the knowledge of
      other angiogenesis inhibitors, we postulate that VASH1 would potentially be a
      biomarker and a candidate for molecular targeted therapy for patients with RCC in
      the future.

PMID- 22865128
TI  - Moderators' summary: outcomes data driving technological advances (session I).

PMID- 22865129
TI  - Axial spine injuries in the current conflicts in Iraq and Afghanistan.
AB  - The burden of injury to the axial skeleton has been substantial relative to the
      conflicts in Iraq and Afghanistan.A coordinated treatment algorithm is required
      that begins with the first encounter on the battlefield and continues through
      treatment at a facility in the continental United States. Translation of these
      spinal trauma classification systems to the battlefield requires that issues of
      expediency,operational limitations and restrictions, and personnel be
      addressed.Current staffing of far-forward echelons in theater may not include a
      spine-trained orthopaedic surgeon, neurosurgeon, or musculoskeletal
      specialist.The classification systems and treatment algorithms being used today
      were formed in the context of a civilian trauma setting. The ready availability
      of advanced medical imaging, sterile operating room theaters, and specialty
      specific intensive care units in these civilian hospitals may make modern spinal
      trauma classification systems less applicable to a far-forward battlefield
      setting. However, efforts must be made to adapt current knowledge in the pursuit
      of a theater-specific, relevant pathway or philosophy of care for the spine
      injured warrior, with implementation as far forward as feasible to ensure the
      best possible clinical outcome.

PMID- 22865130
TI  - Overview of axial skeleton injuries: burden of disease.
AB  - Axial skeletal injury and related illness is a major cause of medical disability
      and force attrition in deployed service members. Predeployment identification of
      at-risk personnel is unreliable. Risk of axial skeletal injury or illness during
      deployment is heterogeneous. Major spinal trauma casualties are uncommon,
      accounting for 1% of casualties, and are usually related to battle injuries.
      These major spinal injuries are often associated with multiple system/anatomic
      injuries. Spinal cord injuries account for 18% of major spinal injuries in
      persons with battle-related spinal injury. Non-battle spine pain, that is, back
      or neck area pain not associated with major trauma, is a significant force
      attrition problem, accounting for 40% of all combat casualty evacuation in some
      years. Personnel attrition due to neck and back pain not associated with major
      trauma is highly variable by unit and exposure, including psychological exposure.
      Return-to-duty rates for both traumatic and atraumatic spine injuries is poor
      (<=15%); this rate is predicted by psychological comorbidities.

PMID- 22865131
TI  - The changing face of disability in the US Army: the Operation Enduring Freedom
      and Operation Iraqi Freedom effect.
AB  - Orthopaedic disorders account for significant disability among adults in the
      United States. Previous studies have demonstrated long-term disability in
      military personnel with musculoskeletal conditions. However, these studies
      focused primarily on battlefield-injured service members and did not evaluate the
      entire population. The goal of this study was to determine and compare the
      disabling conditions of the entire United States Army during peacetime and war.
      We identified the conditions leading to separation from military service before
      and during Operation Iraqi Freedom and Operation Enduring Freedom. During war,
      more soldiers are found to be unfit for duty, and they have more conditions per
      individual that make them unfit. Orthopaedic conditions account for the greatest
      number of soldiers separated from military service at both time points studied
      (ie, January through March 2001, January through March 2009). Back pain and
      osteoarthritis are the two most common causes of separation from military
      service; these conditions are responsible for the most disability during
      peacetime and war.

PMID- 22865132
TI  - Advanced protection technology for ground combat vehicles.
AB  - Just as highway drivers use radar detectors to attempt to stay ahead of police
      armed with the latest radar technology, the Armed Forces are locked in a spiral
      to protect combat vehicles and their crews against the latest threats in both the
      contemporary operating environment and the anticipated operating environment (ie,
      beyond 2020). In response to bigger, heavier, or better-protected vehicles,
      adversaries build and deploy larger explosive devices or bombs. However, making
      improvements to combat vehicles is much more expensive than deploying larger
      explosives. In addition, demand is increasing for lighter-weight vehicles capable
      of rapid deployment. Together, these two facts give the threat a clear advantage
      in the future. To protect vehicles and crews, technologies focusing on detection
      and hit avoidance, denial of penetration, and crew survivability must be combined
      synergistically to provide the best chance of survival on the modern battlefield.

PMID- 22865133
TI  - Long-term disabilities associated with combat casualties: measuring disability
      and reintegration in combat veterans.
AB  - Many physical and mental health problems associated with combat casualties affect
      the reintegration of service members into home and community life. Quantifying
      and measuring reintegration is important to answer questions about clinical,
      research, economic, and policy issues that directly affect combat veterans.
      Although the construct of participation presented in the International
      Statistical Classification of Diseases and Related Health Problems and in the
      International Classification of Functioning, Disability and Health provides a
      theoretical framework with which to understand and measure community
      reintegration in general, a measure was needed that specifically addressed the
      reintegration of combat veterans. To address this need, the Community
      Reintegration for Service Members global outcomes measure was developed. It
      consists of three scales, which measure extent of participation, perceived
      limitations, and satisfaction. The measure was validated in a general sample of
      veterans and in a sample of severely wounded service members. The computer
      adapted test version shows good precision, reliability, construct validity, and
      predictive validity.

PMID- 22865134
TI  - The role of pain management in recovery following trauma and orthopaedic surgery.
AB  - War often serves as a catalyst for medical innovation and progressive change. The
      current conflicts are no exception, particularly in the area of pain management
      of wounded warriors. Morphine administration has served as the primary method of
      battlefield pain management since the American Civil War. Although traditional
      opioid-based pain management is effective, it has significant side effects that
      can complicate recovery and rehabilitation following injury. These side effects
      (eg, sedation, nausea and vomiting, ileus, respiratory depression) can be fatal
      to persons wounded in combat. This fact, along with recent research findings
      indicating that pain itself may constitute a disease process, points to the need
      for significant improvements in pain management in order to adequately address
      current battlefield realities. The US Army Pain Management Task Force evaluated
      pain medicine practices at 28 military and civilian institutions and provided
      several recommendations to enhance pain management in wounded warriors.

PMID- 22865135
TI  - Challenges in severe lower limb injury rehabilitation.
AB  - Restoration of lower limb function following severe injury is a challenge.
      Rehabilitation must take into account psychosocial factors and patient self
      efficacy as well as functional goals. The Return to Run clinical pathway, an
      integrated orthotic and rehabilitation initiative, is an example of goal-oriented
      rehabilitation with periodic assessment aimed at restoring wounded warriors to
      high-level performance following severe lower extremity trauma. Objective
      assessment measures of surgical and rehabilitation interventions are lacking for
      persons with high-level performance demands, such as those required by service
      members. Thus, the Military Performance Laboratory at the Center for the Intrepid
      has established normative data for several physical performance measures, some of
      which are now routinely used to assess service members with severe lower
      extremity trauma. Patient expectations of treatment and rehabilitation are high
      and must be met to avoid poor outcomes attributed to nonanatomic factors.

PMID- 22865136
TI  - Physical performance assessment in military service members.
AB  - Few established measures allow effective quantification of physical performance
      in severely injured service members. We sought to establish preliminary normative
      data in 180 healthy, active-duty service members for physical performance
      measures that can be readily implemented in a clinical setting. Interrater and
      test-retest reliability and minimal detectable change (MDC) values were also
      determined. Physical performance testing included self-selected walking velocity
      on level and uneven terrain, timed stair ascent, the sit-to-stand five times
      test, the four-square step test, and the 6-minute walk test. Data analysis
      included descriptive statistics, intraclass correlation coefficients, and MDC.
      Interrater and test-retest reliability were excellent for all measures
      (intraclass correlation coefficients >0.75). MDC values for timed measures were
      <0.3 seconds for interrater comparisons and <1.5 seconds for between-day
      comparisons. Physical performance measures had a narrow range of normal
      performance and were reliable and stable between days.

PMID- 22865137
TI  - Management of posttraumatic osteoarthritis with an integrated orthotic and
      rehabilitation initiative.
AB  - Posttraumatic osteoarthritis affects approximately 5.6 million Americans
      annually. Those affected are typically younger and more active than persons with
      primary osteoarthritis. Arthrodesis is the typical management option for persons
      with end-stage ankle and subtalar posttraumatic arthritis. Arthroplasty is
      typically reserved for elderly persons. The functional limitations resulting from
      any of these strategies make treatment of this young population challenging.
      Combat wounds frequently lead to severe lower extremity injuries. We present a
      series of patients with severe posttraumatic osteoarthritis of the ankle and
      subtalar joint after combat trauma. They were treated at our institution with an
      integrated orthotic and rehabilitation initiative called the Return To Run
      clinical pathway. This clinical pathway may serve as an alternative or adjunct to
      arthrodesis and arthroplasty for young patients with severe posttraumatic
      osteoarthritis of the ankle and subtalar joint.

PMID- 22865138
TI  - Updates on disaster preparedness and progress in disaster relief.
AB  - Immediately after the January 2010 earthquake in Haiti, many private citizens,
      governmental and nongovernmental organizations, and medical associations
      struggled to mount an effective humanitarian aid response. The experiences of
      these groups have led to changes at their institutions regarding disaster
      preparedness and response to future events. One of the main challenges in a
      humanitarian medical response to a disaster is determining when to end response
      efforts and return responsibility for delivery of medical care back to the host
      nation. For such a transition to occur, the host nation must have the capacity to
      deliver medical care. In Haiti, minimal capacity to deliver such care existed
      before the earthquake, making subsequent transition difficult. If successful,
      several initiatives proposed to improve disaster response and increase surgical
      capacity in Haiti could be deployed to other low- and middle-income countries.

PMID- 22865139
TI  - Measurement of functional outcomes in the Major Extremity Trauma Research
      Consortium (METRC).
AB  - Measurement of functional outcome is a central tool in the assessment of the
      human and economic consequences of trauma. As such, functional outcome is the
      ideal basis against which to judge the efficacy of surgical approaches, drugs,
      and devices in the context of evidence-based medicine. A well-designed outcome
      measurement plan improves the validity of clinical research, facilitates the
      optimal use of limited research resources, and maximizes opportunities for future
      secondary data analyses. However, a key challenge in the development of a study
      measurement plan is the identification of appropriate, practical, well-validated
      measures. The Major Extremity Trauma Research Consortium (METRC) is a large 5
      year research effort to develop and conduct multicenter clinical studies relevant
      to the treatment and outcomes of orthopaedic trauma. METRC is funded to conduct
      nine clinical studies. One of the main goals is to benefit from the consortium
      approach by standardizing data collection across these studies. METRC
      investigators have developed a standard set of measurement instruments designed
      to examine outcomes across a defined set of key domains: complications,
      depression, posttraumatic stress disorder, pain, activity and participation,
      health-related quality of life, patient satisfaction, and healthcare utilization.
      In addition, METRC investigators have developed a standard set of
      sociodemographic and clinical covariates to be collected across all studies.

PMID- 22865140
TI  - Posttraumatic osteoarthritis caused by battlefield injuries: the primary source
      of disability in warriors.
AB  - The Army Physical Evaluation Board results for wounded warriors from a previously
      described cohort were reviewed to identify permanently disabling conditions and
      whether the conditions were preexisting or caused by battlefield injury.
      Arthritis was the most common unfitting condition in this cohort, with 94.4% of
      cases attributed to combat injury and only 5.6% attributed to preexisting
      conditions or documented in the health records prior to battle injury. The most
      common causes of injury that resulted in arthritis were intra-articular fractures
      secondary to explosions, traumatic arthrotomies resulting from fragment
      projectiles, and gunshot wounds. Arthritis was recognized as a disabling
      condition an average of 19 +/- 10 months after injury. Research is needed to
      enhance prevention and management of joint injuries in order to minimize the
      disabling effects of joint degeneration in this young patient population.

PMID- 22865141
TI  - Factors associated with mortality in combat-related pelvic fractures.
AB  - Pelvic fractures were sustained by >=26% of service members who died during
      Operation Enduring Freedom and Operation Iraqi Freedom in 2008. To determine
      factors associated with patient mortality following combat-related pelvic
      fracture (CRPF), the Joint Theater Trauma Registry database was searched to
      identify service members who survived CRPF sustained in the year 2008 (group 1),
      and the Armed Forces Medical Examiner System was searched to identify
      nonsurvivors of such trauma in the same year (group 2). Stable pelvic ring
      injuries were associated with a lower mortality rate than were unstable injuries
      when controlling for large-vessel and anatomic brain injuries (43% and 85%,
      respectively; P < 0.05). Associated injuries that were significant predictors of
      mortality included large-vessel, anatomic brain, cardiopulmonary, and solid organ
      abdominal (P < 0.05). Compared with a similar cohort of nonsurvivors, persons who
      survive CRPF have less severe pelvic fractures and associated injuries. In
      addition, pelvic fractures secondary to direct combat (ie, blast-related blunt
      injury, penetrating injury) were significantly more lethal than were those caused
      by mechanisms analogous to civilian trauma.

PMID- 22865142
TI  - Evolution of acute orthopaedic care.
AB  - Current combat battlefield injuries are among the most complex and challenging
      orthopaedic cases. These injuries carry high risks for exsanguination and global
      contamination of extensive soft-tissue and complicated bony injuries. Military
      orthopaedic surgeons must employ the latest advances in acute combat casualty
      care to achieve favorable outcomes. Adaptive changes over the past 10 years of
      war have given today's surgeons the armamentarium to optimize patient care.
      Innovative methods of damage control resuscitation and surgery have led to
      increased survival. However, the fundamentals of surgical hemostasis and
      decontamination remain critical to successful management. The acute treatment of
      combat casualties involves a continuum of care from the point of injury through
      transport out of theater. Future research and education are paramount to better
      prepare military orthopaedic surgeons to further increase survivability and
      enhance the outcomes of service members with complex wounds.

PMID- 22865143
TI  - Evolution of orthopaedic reconstructive care.
AB  - The patterns and severity of injury sustained by service members have
      continuously evolved over the past 10 years of combat in Iraq and Afghanistan.
      The 2010 surge of combat troops into Afghanistan, combined with a transition to
      counterinsurgency tactics with an emphasis on dismounted operations, resulted in
      increased exposure of US service members to improvised explosive devices and a
      new pattern of injury termed dismounted complex blast injury. This constellation
      of injuries typically includes multiple extremity injuries, high bilateral
      transfemoral amputations, amputated or mangled upper extremities, open pelvis
      fractures, and injury to the perineal and/or genital regions. These
      polytraumatized patients frequently present with head, abdominal, and
      genitourinary injuries, as well. Traditional methods of reconstruction must be
      optimized because tissue availability may be limited.

PMID- 22865144
TI  - Evolution of orthopaedic rehabilitation care.
AB  - Rehabilitation following surgical reconstruction for combat-related extremity
      injuries sustained in the current conflicts in Iraq and Afghanistan has been
      challenging. The goal of rehabilitation is to restore limb function to facilitate
      the reintegration of patients with these severe injuries into society. The US
      Department of Defense has developed a network of rehabilitation centers of
      excellence within the military healthcare system in collaboration with the US
      Department of Veterans Affairs to optimize outcomes using technologic and
      systemic advances in prostheses in patients who have undergone limb salvage
      procedures or amputation. Managing pain during rehabilitation and optimizing
      function following high bilateral lower extremity amputation remains a clinical
      challenge. However, continued research is likely to improve outcomes in this
      severely injured patient population. To that end, two research consortia, the
      Bridging Advanced Developments for Exceptional Rehabilitation and the Center for
      Rehabilitation Sciences Research, have recently been created to address
      identified knowledge gaps.

PMID- 22865145
TI  - Orthopaedic outcomes: combat and civilian trauma care.
AB  - Important advances have been made in the management of complex trauma through
      careful scientific analysis of outcomes. Outcomes analysis in combat extremity
      trauma is exemplified and highlighted by scholarly work in the treatment of
      catastrophic lower extremity trauma. The success of this line of research in
      civilian trauma is exemplified by the Lower Extremity Assessment Project (LEAP)
      study on the outcomes of civilian lower extremity trauma. This highly successful
      effort was followed by the Military Extremity Trauma Amputation/Limb Salvage
      (METALS) study. Current ongoing analysis of both the LEAP and METALS studies by
      the Major Extremity Trauma Research Consortium seeks to compare and contrast the
      similarities and differences of both studies and to advance evidence-based
      patient-centered care. The effects of psychological trauma on the injured
      individual underscore the global effect of severe trauma and the need for a
      multidisciplinary approach to trauma care. Statistical modeling is being used to
      analyze outcomes to further the ability to scientifically and definitively
      determine the best practices for patient care.

PMID- 22865146
TI  - Axioms altered with research.
AB  - The medical community is actively engaged in research to provide the highest
      level of evidence to support clinical practice. The care of wounded warriors
      creates unique challenges, and conducting research that provides evidence for
      clinical practice is important to outcomes in this patient population. When the
      current wars began, much debate centered on the best way to care for wounded
      warriors. To address these concerns, we use a MythBusters format, based on the
      popular television show, to describe how recent research has dispelled some
      earlier misconceptions and clarify how clinical practice has been changed. In
      addition, we assess the progress that has been made on addressing the original
      prioritized research objectives of the first Extremity War Injuries symposium.

PMID- 22865147
TI  - Special topics.
AB  - Concerning the past decade of war, three special topics were examined at the
      Extremity War Injuries VII Symposium. These topics included the implementation of
      tourniquets and their effect on decreasing mortality and the possibility of
      transitioning the lessons gained to the civilian sector. In addition, the
      training of surgeons for war as well as residents in a wartime environment was
      reviewed.

PMID- 22865148
TI  - Reprioritization of research for combat casualty care.
AB  - Since the beginning of the conflicts in Iraq and Afghanistan more than a decade
      ago, much has been learned with regard to combat casualty care. Although progress
      has been significant, knowledge gaps still exist. The seventh Extremity War
      Injuries symposium, held in January 2012, reviewed the current state of knowledge
      and defined knowledge gaps in acute care, reconstructive care, and rehabilitative
      care in order to provide policymakers information on the areas in which research
      funding would be the most beneficial.

PMID- 22865149
TI  - Extremity war injuries: current management and research priorities.

PMID- 22865150
TI  - Sensory, yield and quality differences between organically and conventionally
      grown winter wheat.
AB  - BACKGROUND: Consumers expect organic produce to have higher environmental, health
      and sensory related qualities than conventional produce. In order to test sensory
      differences between bio-dynamically, bio-organically and conventionally grown
      winter wheat (Triticum aestivum L., cv. Runal), we performed double-blinded
      triangle tests with two panels on dry wholemeal flour from the harvest years
      2006, 2007 and 2009 and from two field replicates of the 'DOK' long-term farming
      system comparison field trial near Basel, Switzerland. Yield and quality
      parameters were also assessed. RESULTS: Significant farming system effects were
      found for yield (up to 42% reduction in the organic system), thousand kernel
      weight, hectolitre weight and crude protein content across the three years. In
      the triangle tests one out of 12 pair-wise farming system comparisons (PFSCs) on
      wholemeal flour made from the different wheat samples showed significant sensory
      differentiation (between bio-dynamically and conventionally grown wheat). When
      all data from the three harvest years and two panels were aggregated, a
      statistically significant effect (P = 0.045) of PFSCs on the number of correct
      answers became evident. CONCLUSIONS: Although testing of dry wholemeal flour was
      very challenging for panellists, we were able to show that sensory differences
      between farming systems can occur.

PMID- 22865151
TI  - The modality shift experiment in adults and children with high functioning
      autism.
AB  - This study used the modality shift experiment, a relatively simple reaction time
      measure to visual and auditory stimuli, to examine attentional shifting within
      and across modalities in 33 children and 42 adults with high-functioning autism
      as compared to matched numbers of age- and ability-matched typical controls. An
      exaggerated "modality shift effect" relative to the TD children occurred for the
      children with autism in conditions involving the reaction time when shifting from
      sound to light but not from light to sound. No exaggerated MSE was found for the
      adults with autism; rather, their responses were characterized by a generalized
      slowness relative to the adults with TD. These results suggest a lag in
      maturational development in autism in basic information processing mechanisms.

PMID- 22865152
TI  - Eye-hand coordination in children with high functioning autism and Asperger's
      disorder using a gap-overlap paradigm.
AB  - We investigated eye-hand coordination in children with autism spectrum disorders
      (ASD) in comparison with age-matched normally developing peers. The eye-hand
      correlation was measured by putting fixation latencies in relation with pointing
      and key pressing responses in visual detection tasks where a gap-overlap paradigm
      was used and compared to fixation latencies in absence of manual response. ASD
      patients showed less efficient eye-hand coordination, which was particularly
      evident when pointing towards a target was being fixated. The data of normally
      developing participants confirmed that manual gap effects are more likely for
      more complex hand movements. An important discrepancy was discovered in
      participants with ASD: beside normal eye gap effects, they showed no concurrent
      hand gap effects when pointing to targets. This result has been interpreted as a
      further sign of inefficient eye-hand coordination in this patient population.

PMID- 22865153
TI  - Prevention of quality-of-life deterioration with light therapy is associated with
      changes in fatigue in women with breast cancer undergoing chemotherapy.
AB  - PURPOSE: During chemotherapy, women with breast cancer not only experience poor
      quality of life (QOL), they also have little exposure to bright light, which has
      been shown to be associated with depression, fatigue, and poor sleep in other
      chronic illnesses. This study examined whether increased light exposure would
      have a positive effect on QOL. METHODS: Thirty-nine women with stage I-III breast
      cancer scheduled to receive >= 4 cycles of chemotherapy were randomized to a
      bright white light (BWL, n = 23) or dim red light (DRL, n = 16) treatment group.
      Data were collected before (baseline) and during cycles 1 and 4 of chemotherapy.
      Light was administered via a light box (Litebook((r)), Ltd.). QOL was assessed
      with the Functional Assessment of Cancer Therapy-Breast (FACT-B) and the
      Functional Outcomes of Sleep Questionnaire (FOSQ). RESULTS: Compared with
      baseline, the DRL group demonstrated significant decline in QOL during the
      treatment weeks of both cycles (all ps < 0.02), whereas the BWL group had no
      significant decline (all ps > 0.05). Mixed model analyses revealed that there was
      a group-by-time interaction for FOSQ at the treatment week of cycle 4, and this
      interaction was mediated by fatigue. CONCLUSION: The data suggest that increased
      exposure to bright light during chemotherapy may prevent the decline in QOL via
      preventing the increase in fatigue.

PMID- 22865154
TI  - Management of post-traumatic nightmares: a review of pharmacologic and
      nonpharmacologic treatments since 2010.
AB  - Nightmares are a universal and timeless phenomenon. They occur in most healthy
      adults as well as a significant portion of clinical populations, especially those
      exposed to trauma. Considerable advances in the pharmacological and psychological
      treatment of post-traumatic nightmares have occurred over the last decade with
      continuing advances in psychological interventions over the last few years.
      Pharmacologically, the medication prazosin is showing robust clinical effects
      with minimal side effects. Psychologically, imagery rehearsal therapy commands
      the greater portion of the nightmare literature due to its established efficacy.
      These issues are reviewed in the following paper along with recommendations for
      future studies.

PMID- 22865155
TI  - Is chronic insomnia a precursor to major depression? Epidemiological and
      biological findings.
AB  - Insomnia has been found to be a clinical predictor of subsequent depression.
      Nevertheless the biological processes underlying this causal relationship are yet
      not fully understood. Both conditions share a common imbalance of the arousal
      system. Patients with insomnia present fragmented REM sleep, which probably
      interferes with basal processes of emotion regulation. The interaction between
      the arousal and the affective system with the persistence of the disorder could
      slowly alter also the cognitive system and lead to depression. Although
      preliminary results seem to support this hypothesis, data are still too few to
      make valid conclusions.

PMID- 22865156
TI  - Cognitive-behavioral therapy for the management of insomnia comorbid with mental
      disorders.
AB  - Insomnia is frequently comorbid with psychiatric conditions, mostly depression
      and anxiety disorders. Because disturbed sleep is a symptom of most major mental
      disorders, it has been traditionally assumed that effective treatment of the
      psychiatric condition will resolve the coincident insomnia also. However,
      insomnia often persists after successful treatment of the comorbid mental
      disorder, suggesting that insomnia often warrants separate treatment attention.
      Cognitive-behavioral therapy (CBT) is a well established and efficacious
      treatment for insomnia. Most evidence supporting the efficacy of CBT comes from
      studies conducted with patients suffering from primary insomnia, yet over the
      past 20 years there has been growing support for the use of cognitive-behavioral
      insomnia intervention for patients with comorbid psychiatric conditions. Overall,
      promising results have been obtained from these studies, not only with regard to
      insomnia improvement but also concurrent improvements in comorbid psychiatric
      conditions. In this article we review recent studies in this area with particular
      focus on treatment of insomnia in the context of depression, post-traumatic
      stress disorder, and alcohol dependence.

PMID- 22865157
TI  - Hybrid SPECT-CT for characterizing isolated vertebral lesions observed by bone
      scintigraphy: comparison with planar scintigraphy, SPECT, and CT.
AB  - PURPOSE: We aimed to assess the role of single photon emission computed
      tomography-computed tomography (SPECT-CT) for characterizing isolated vertebral
      lesions observed by bone scintigraphy compared to planar scintigraphy, SPECT, and
      CT, and to evaluate the impact of SPECT-CT on patient management. MATERIALS AND
      METHODS: Data from 99 patients (mean age, 52.4+/-18.9 years; females, 58.5%) with
      108 isolated vertebral lesions visible on planar bone scintigraphy, who had
      undergone SPECT-CT of a selected volume, were retrospectively analyzed. Planar
      scintigraphy, SPECT, CT, and SPECT-CT images were independently evaluated in
      separate sessions to minimize recall bias. A scoring scale of 1 to 5 was used,
      with 1 being definitely metastatic, 2 most likely metastatic, 3 indeterminate, 4
      most likely benign, and 5 definitely benign. Sensitivity, specificity, and
      predictive values were calculated; a score <=3 was defined as metastatic. The
      areas under the receiver operating characteristic curve were calculated and
      compared. Clinical and imaging followup with or without histopathology were used
      as a reference standard. RESULTS: Among the 108 lesions, 49 were indeterminate on
      planar scintigraphy, 16 on SPECT, and one each on SPECT-CT and CT. SPECT-CT was
      superior to both planar scintigraphy (P < 0.001) and SPECT alone (P = 0.014), but
      not to CT (P = 0.302). CT was superior to planar scintigraphy (P < 0.001) but
      only slightly superior to SPECT (P = 0.063). SPECT-CT correctly characterized 96%
      of the indeterminate lesions observed by planar scintigraphy. SPECT-CT had an
      impact on the clinical management of 60.6% patients compared to planar
      scintigraphy and 18.1% compared to SPECT. CONCLUSION: SPECT-CT is better than
      planar scintigraphy and SPECT alone, but not CT alone, for characterizing
      equivocal vertebral lesions that are observed by bone scintigraphy, thus SPECT-CT
      can have a significant impact on patient management.

PMID- 22865158
TI  - Adaptive transport of folic acid across renal epithelia in folate-deficient rats.
AB  - Folate (vitamin B(9)) is an essential vitamin for a wide spectrum of biochemical
      reactions; however, unlike bacteria and plants, mammals are devoid of folate
      biosynthesis and thus must obtain this cofactor from exogenous sources. The
      activities of folate transporters on the kidneys play an important role in
      conserving folate excretion and reabsorption across the apical membrane of the
      renal proximal tubules. The different transport system activities may become
      identifiable in response to external stimuli, such as folate availability and
      exposure to chemotherapeutic agents. We have explored the effect of folate
      deficiency on the activity and expression of folate transporters in rat kidneys.
      Wistar rats were fed a folate-containing diet (2 mg folic acid kg(-1) diet) or a
      folic acid-free diet over a 3-month period, and mechanisms of folate transport
      were studied in renal brush border membrane vesicles and basolateral membrane
      vesicles. The renal folate uptake process is saturable and pH dependent, and it
      involves the folate receptor and reduced folate carrier (RFC) systems and
      possibly the proton coupled folate transporter (PCFT) system. We found that
      folate deficiency increased the renal brush border membrane and basolateral
      folate uptake by increasing the number of transporter molecules. The observed up
      regulation of mRNA expression was also associated with a significant increase in
      RFC and PCFT expression at the protein level.

PMID- 22865159
TI  - Bilateral ischiofemoral impingement in a patient with hereditary multiple
      exostoses.
AB  - The skeletal anatomy of the hip provides two main locations for impingement:
      abnormal contact between the acetabulum and femur (femoroacetabular impingement)
      or between the ischium and femur (ischiofemoral impingement). We report a case of
      bilateral ischiofemoral impingement in a patient with hereditary multiple
      exostoses. The association of exostoses and femoral metaphyseal widening resulted
      in the narrowing of the ischiofemoral spaces. Pain was improved on the left side
      by resection of the ischial exostosis.

PMID- 22865161
TI  - Cloud based emergency health care information service in India.
AB  - A hospital is a health care organization providing patient treatment by expert
      physicians, surgeons and equipments. A report from a health care accreditation
      group says that miscommunication between patients and health care providers is
      the reason for the gap in providing emergency medical care to people in need. In
      developing countries, illiteracy is the major key root for deaths resulting from
      uncertain diseases constituting a serious public health problem. Mentally
      affected, differently abled and unconscious patients can't communicate about
      their medical history to the medical practitioners. Also, Medical practitioners
      can't edit or view DICOM images instantly. Our aim is to provide palm vein
      pattern recognition based medical record retrieval system, using cloud computing
      for the above mentioned people. Distributed computing technology is coming in the
      new forms as Grid computing and Cloud computing. These new forms are assured to
      bring Information Technology (IT) as a service. In this paper, we have described
      how these new forms of distributed computing will be helpful for modern health
      care industries. Cloud Computing is germinating its benefit to industrial sectors
      especially in medical scenarios. In Cloud Computing, IT-related capabilities and
      resources are provided as services, via the distributed computing on-demand. This
      paper is concerned with sprouting software as a service (SaaS) by means of Cloud
      computing with an aim to bring emergency health care sector in an umbrella with
      physical secured patient records. In framing the emergency healthcare treatment,
      the crucial thing considered necessary to decide about patients is their previous
      health conduct records. Thus a ubiquitous access to appropriate records is
      essential. Palm vein pattern recognition promises a secured patient record
      access. Likewise our paper reveals an efficient means to view, edit or transfer
      the DICOM images instantly which was a challenging task for medical practitioners
      in the past years. We have developed two services for health care. 1. Cloud based
      Palm vein recognition system 2. Distributed Medical image processing tools for
      medical practitioners.

PMID- 22865160
TI  - Apparent motion perception in patients with paranoid schizophrenia.
AB  - Impaired perceptual inference has been suggested to be at the core of positive
      symptoms in schizophrenia. Apparent motion (AM) is a visual illusion in which
      perceptual inference gives rise to the experience of a single object moving back
      and forth when two spatially separated objects are flashed in alternation. Here,
      we investigated the strength of AM perception in patients with paranoid
      schizophrenia. Patients were less susceptible to the illusion as indicated by a
      lower probability of motion perception at the individual's optimal presentation
      frequency for AM. In addition, the probability of AM perception was inversely
      related to delusional conviction in the patient group. These results suggest that
      schizophrenia may be associated with a reduced susceptibility to visual phenomena
      that commonly rely on perceptual inference.

PMID- 22865162
TI  - Context-dependent motor skill: perceptual processing in memory-based sequence
      production.
AB  - Previous studies have shown that motor sequencing skill can benefit from the
      reinstatement of the learning context-even with respect to features that are
      formally not required for appropriate task performance. The present study
      explored whether such context-dependence develops when sequence execution is
      fully memory-based-and thus no longer assisted by stimulus-response translations.
      Specifically, we aimed to distinguish between preparation and execution
      processes. Participants performed two keying sequences in a go/no-go version of
      the discrete sequence production task in which the context consisted of the color
      in which the target keys of a particular sequence were displayed. In a subsequent
      test phase, these colors either were the same as during practice, were reversed
      for the two sequences or were novel. Results showed that, irrespective of the
      amount of practice, performance across all key presses in the reversed context
      condition was impaired relative to performance in the same and novel contexts.
      This suggests that the online preparation and/or execution of single key presses
      of the sequence is context-dependent. We propose that a cognitive processor is
      responsible both for these online processes and for advance sequence preparation
      and that combined findings from the current and previous studies build toward the
      notion that the cognitive processor is highly sensitive to changes in context
      across the various roles that it performs.

PMID- 22865163
TI  - Strong anticipation: complexity matching in interpersonal coordination.
AB  - A subtle coordination occurs within complex systems, between multiple nested sub
      systems. This intra-system coordination can be detected by the presence of 1/f
      fluctuations produced by the system. But coordination can occur also between
      systems. Interpersonal coordination has been studied from a local point of view
      until now, focusing on macroscopic interactions. But the recent concept of strong
      anticipation introduced by Dubois (Lect Notes Comput Sci 2684:110-132, 2003)
      suggests that interactions could occur on multiple levels between complex
      systems. The hypothesis is that time series in interpersonal synchronization
      present a matching of the complexity index (fractal exponent). Moreover, it is
      argued that this matching is not a consequence of short-term adaptations but
      reveals a global coordination between participants. Eleven pairs of participants
      oscillated a hand-held pendulum in the in-phase pattern for 11 min, in three
      conditions where the coupling strength was manipulated by the perceptual
      feedbacks. The results show a high correlation between fractal exponents
      irrespective of the coupling strength, and a very low percentage of local cross
      correlations between time series appear at lag 0 and lag 1. These results suggest
      that interpersonal coordination, and more globally synchronization of
      participants with natural environments, is based on non-local time scales.

PMID- 22865164
TI  - Hormonal contraceptive use and discontinuation because of dissatisfaction:
      differences by race and education.
AB  - The unintended pregnancy rate in the United States remains high, and there are
      large race and education differences in unintended pregnancy and fertility. These
      differences make it important to study race and education differences in
      contraceptive behavior. Using nationally representative data from the 2002
      National Survey of Family Growth, this study examines the effects of race and
      education on the likelihood that women have ever used particular types of
      hormonal contraception and have ever discontinued hormonal contraception because
      of dissatisfaction. The results show that blacks and Latinas were more likely to
      have used injectable contraceptives ("the shot") and less likely to have used
      oral contraceptives ("the pill") than were white women. Women with less education
      were more likely than college-educated women to have used the shot but there were
      no significant education differences in use of the pill. Among women who had ever
      used hormonal birth control, those with less than a college degree were more
      likely than college-educated women to discontinue the birth control because of
      dissatisfaction. However, net of education, this study found no significant
      racial/ethnic differences in discontinuation. The most commonly stated reason for
      discontinuation because of dissatisfaction was side effects.

PMID- 22865165
TI  - Recent advances in polymer colloidal crystal lasers.
AB  - Colloids with a size in the nanometres to micrometres range are frequently used
      in both fundamental research and industrial applications. In this context,
      colloidal crystals (CCs)-3D ordered arrays of monodispersed colloidal
      microparticles with a diameter of several hundred nanometres-have garnered a
      great deal of attention in the intriguing research realm of photonic crystals
      (PCs) due to the feasible and high-throughput 3D-PC fabrication with CCs. For
      optoelectronic applications, it is of prime importance to construct 3D-PCs with
      photonic band-gaps (PBGs) in the visible wavelength range. With regard to
      photonic device applications, many reports have been made on a wide variety of
      optical reflection sensors and displays using CCs that shift the visible PBG
      wavelength in response to external stimuli. This Minireview describes the
      research progress in the investigation of CCs and their laser applications. We
      highlight not only the research background of CCs as 3D-PCs, but also new
      potential applications of CCs as flexible and widely tunable lasers by low
      threshold optical excitation.

PMID- 22865166
TI  - Molecular characterization of a new lytic bacteriophage isolated from cheese
      whey.
AB  - In this study, we isolated and characterized a lytic Lactococcus lactis
      bacteriophage from the sera of a failed fermentation. The phage was isolated and
      cultured in L. lactis subsp. cremoris in M17 medium. The isolated bacteriophage
      was characterized by multiplex PCR, pulsed-field electrophoresis, DNA restriction
      digestion, analysis of the N-terminal sequence of the phage major structural
      protein, transmission electron microscopy and sequencing and analysis of a
      conserved fragment of its genome. Analysis of the viral genome indicates that its
      genome is composed of a DNA strand of approximately 48 kb in length, and PCR and
      microscopy confirmed that IL-P1 belongs to the group of 936-type phages in the
      family Siphoviridae, which is the most abundant type of lactococcal virus in
      dairy products worldwide. To our knowledge, this is the first report of a virus
      within this family that has a presumptive genome larger than 40 kb.

PMID- 22865168
TI  - Doctor for Society: a corner to showcase exemplary models and promote
      volunteerism.

PMID- 22865167
TI  - A multicenter, prospective, clinical trial evaluating a novel adhesive baseplate
      (Provox StabiliBase) for peristomal attachment of postlaryngectomy pulmonary and
      voice rehabilitation devices.
AB  - OBJECTIVES/HYPOTHESIS: Assessment of a novel adhesive baseplate (Provox
      StabiliBase) for heat and moisture exchanger (HME) and/or automatic speaking
      valve (ASV) application. STUDY DESIGN: Prospective, clinical, multicenter trial.
      METHODS: This was a trial in laryngectomized patients comparing their usual
      adhesive with the trial adhesive. Primary outcome measure was overall patient
      preference; additional outcome parameters possibly explaining patients'
      preferences were 1) patient tolerance and preference with respect to daily
      handling of the adhesive; 2) adhesive lifespan, and 3) voice and speech with the
      adhesives. Study specific questionnaires, visual analog scales, patients'
      diaries, and stoma assessments were used for data collection. RESULTS: In total,
      58 of the 65 laryngectomized individuals entered in the study completed the
      trial. Patients' overall preference for the new device was high (76%; P < .001).
      Significantly better performance was found for the trial adhesive with respect to
      ease of application (P = .034), fit (P < .001), and air leakage through the
      adhesive (P < .001). Comfort and stoma depth correlated weakly (r = 0.297; P =
      .024; deeper stoma-more comfort with StabiliBase). The adhesive lifespan with HME
      is significantly increased (1.7 times and 15.7 hours-plus airtight use; P <
      .001). This longer lifespan coincided with somewhat increased dirtying of the
      adhesive (P = .02). There were no serious adverse events. CONCLUSIONS: The
      StabiliBase adhesive for peristomal attachment of HMEs and/or ASVs was preferred
      by 76% of study participants and showed a promising prolonged lifespan. This new
      device further increases the options for stoma attachment in laryngectomized
      individuals, and subsequently the availability of optimal voice and pulmonary
      rehabilitation for a larger proportion of patients.

PMID- 22865169
TI  - Dettol poisoning and the need for airway intervention.
AB  - OBJECTIVES. To (1) characterise the clinical features of Dettol poisoning on a
      territory-wide basis, (2) assess the need for airway intervention after such
      poisoning and its time frame after ingestion, and (3) identify predictors for
      such an intervention. DESIGN. Case series. SETTING. Sixteen accident and
      emergency departments in Hong Kong. PATIENTS. Patients with Dettol ingestion who
      presented within 48 hours of ingestion from July 2005 to June 2009, derived from
      the database of the Hong Kong Poison Information Centre. RESULTS. In all, 213
      patient records were identified, of which 36 were excluded based on pre-defined
      criteria and 177 were analysed. Among the latter, the median age was 32 (range, 2
      95) years and the male-to-female ratio was 1:2.7 (48:129). Intentional ingestion
      constituted the majority (95%) of cases. The most common symptoms were related to
      the local irritative/corrosive effects on the aero-digestive tract, such as
      gastro-intestinal upset and localised throat pain. Airway intervention was
      required in 14 (8%) patients. All interventions were performed within 12 hours of
      Dettol ingestion and three cases involved re-intubation after extubation.
      Univariate analysis showed that a Glasgow Coma Scale score of <8, older age, a
      larger amount ingested, lip swelling, lung crackles, and wheezing were all
      associated with airway intervention. In the multivariate analysis using forward
      stepwise logistic regression, only coma (Glasgow Coma Scale score of <8) remained
      statistically significant. CONCLUSIONS. Delayed airway obstruction (>12 hours
      after Dettol ingestion) is unlikely. For those who are intubated, careful
      assessment of airway adequacy before extubation is strongly recommended to avoid
      extubation failure and subsequent re-intubation. Patients in coma (Glasgow Coma
      Scale score of <8) should prompt airway intervention.

PMID- 22865170
TI  - Reperfusion strategy for ST-segment elevation myocardial infarction: trend over a
      10-year period.
AB  - OBJECTIVES. To review the 10-year trend of reperfusion strategies in patients
      with ST-segment elevation myocardial infarction, and the adoption rate of
      percutaneous coronary interventions as opposed to thrombolytic therapy. Also to
      explore why some patients did not receive reperfusion therapy, and document
      changes in reperfusion strategies after the introduction of primary percutaneous
      coronary intervention programmes. DESIGN. Case series. SETTING. A regional
      hospital, Hong Kong. PATIENTS. All patients with ST-segment elevation myocardial
      infarction from January 2000 to December 2009. RESULTS. There were 1835 patients
      with ST-segment elevation myocardial infarction in that period, of which 1179
      (64.3%) received reperfusion therapy (thrombolytic therapy, 46.0%; primary
      percutaneous coronary intervention, 17.5%; emergency coronary artery bypass
      graft, 0.7%). After introduction of the primary percutaneous coronary
      intervention programme, significantly more ST-segment elevation myocardial
      infarction cases underwent that particular intervention (1.6% in 2000 increasing
      to 30.6% in 2009), while the proportion receiving thrombolytic therapy declined
      (57.4% in 2000 decreasing to 35.0% in 2009). Seven reasons for no reperfusion
      therapy were identified. The commonest ones were delayed presentation (45.1%),
      succumbed before reperfusion (16.0%), multiple medical co-morbidities (15.2%),
      and contra-indication to thrombolytic therapy (14.8%). The proportion without
      reperfusion therapy due to a contra-indication to thrombolytic therapy declined
      (22.7% in 2000 decreasing to 4.9% to 2009), whilst an increasing proportion
      received primary percutaneous coronary interventions. CONCLUSIONS. Primary
      percutaneous coronary intervention is increasingly used as the reperfusion
      therapy in ST-segment elevation myocardial infarction and is replacing
      thrombolytic therapy, though the latter still remains a mainstay of therapy. A
      significant proportion of ST-segment elevation myocardial infarction cases
      received no reperfusion due to various reasons.

PMID- 22865171
TI  - Outcome of adult critically ill patients mechanically ventilated on general
      medical wards.
AB  - OBJECTIVE. A significant number of critically ill mechanically ventilated
      patients are not admitted to the Intensive Care Unit but are cared for on general
      wards. This study looked at the outcome of these patients. DESIGN. Case series.
      SETTING. A 1100-bed tertiary hospital in Hong Kong. PATIENTS. All adult patients
      admitted in a 2.5-year period who received invasive mechanical ventilation on
      general medical wards without admission to Intensive Care Unit or other special
      care areas. INTERVENTIONS. Invasive mechanical ventilation. MAIN OUTCOME
      MEASURES. The observed number of deaths, the expected number of deaths as derived
      from the Mortality Probability Model II system admission model, and other
      morbidity measures. RESULTS. Among 755 patients studied, the observed number of
      deaths was 673, which amounts to a mortality of 89.1%. The expected number of
      deaths was 570. The risk-standardised mortality ratio was 1.18 (95% confidence
      interval, 1.09-1.28; P<0.0005). Patients with chronic obstructive pulmonary
      disease had the lowest mortality rate of 70.8% (P<0.005). The post-cardiac arrest
      subgroup had the highest mortality of 99.0%. CONCLUSIONS. There was a worse-than
      predicted survival in the absence of Intensive Care Unit care for the critically
      ill patients who received mechanical ventilation on general wards. Patients with
      chronic obstructive pulmonary disease warranted more Intensive Care Unit
      admissions. Early discontinuation of invasive support should be seriously
      considered in the post-cardiac arrest patients.

PMID- 22865172
TI  - Early outcome after emergency gastrectomy for complicated peptic ulcer disease.
AB  - OBJECTIVE. To analyse outcomes of patients who underwent emergency gastrectomy
      for complicated peptic ulcer disease. DESIGN. Prognostic study on a historical
      cohort. SETTING. A regional hospital in Hong Kong. PATIENTS. Patients who
      underwent emergency gastrectomy from 2000 to 2009 in our hospital. MAIN OUTCOME
      MEASURES. Primary outcome measures were in-hospital mortality and the predictors
      of such deaths. Secondary outcome measures were 7-day mortality, 30-day
      mortality, and morbidities. RESULTS. In all, 112 patients had emergency
      gastrectomies performed for complicated peptic ulcer disease during the study
      period. In-hospital mortality was 30%. In the univariate analysis, old age,
      duodenal ulcer, failed primary surgery, gastrojejunostomy anastomosis for
      reconstruction, hand-sewn technique for duodenal stump closure, use of a sump
      drain, low haemoglobin level, preoperative blood transfusion, prolonged
      prothrombin time, and high creatinine or bilirubin levels were associated with an
      increased risk of in-hospital mortality. In the multivariate analysis, failed
      primary surgery, old age, and high creatinine level turned out to be independent
      risk factors. CONCLUSIONS. Emergency gastrectomy should be considered seriously
      as the primary treatment option in appropriately selected elderly patients,
      instead of salvage procedures to repair a perforation or control bleeding by
      plication.

PMID- 22865173
TI  - The profile of women who seek emergency contraception from the family planning
      service.
AB  - OBJECTIVES. To review the profile of emergency contraceptive users, their reasons
      for using emergency contraception, and whether they use it correctly. DESIGN.
      Retrospective analysis of medical records. SETTING. Six Birth Control Clinics and
      three Youth Health Care Centres of the Family Planning Association of Hong Kong.
      PARTICIPANTS. Women requesting emergency contraception between 2006 and 2008.
      MAIN OUTCOME MEASURES. Demographics of emergency contraception users, reasons for
      requesting emergency contraception, number of times the subject had unprotected
      intercourse before emergency contraception use, type of emergency contraception
      provided, coitus-treatment intervals, and outcomes. RESULTS. A total of 11 014
      courses of emergency contraception were provided, which included 10 845 courses
      of levonorgestrel-only pills, 168 intrauterine contraceptive devices, and one
      course of pills plus an intrauterine contraceptive device. The mean age of the
      users was 30 years. Two thirds (65.6%) were nulliparous and 64.9% had not had a
      previous abortion. Their major reasons for requesting emergency contraception
      were: omission of contraceptive at the index intercourse (38.9%), condom
      accidents (38.0%), and non-use of any regular contraceptives (20.6%). Non-users
      of contraceptives were more likely to have had a previous abortion. In all, 97.9%
      of women took emergency contraception within 72 hours of their unprotected
      intercourse; 98% had had a single act of unprotected intercourse. None of the
      intrauterine contraceptive device users became pregnant. The failure rate for
      emergency contraceptive pills was 1.8%. CONCLUSIONS. Women requested emergency
      contraception because contraceptives were omitted or condom accidents. Health
      care providers should focus on motivating women with a history of abortion to use
      contraceptives, and ensure that condom users know how to use them correctly. Most
      women followed instructions on the use for emergency contraception and their
      outcomes were satisfactory.

PMID- 22865174
TI  - Virtual blood banking in Hong Kong.
AB  - OBJECTIVE. To review our experience in virtual blood banking for intra-operative
      transfusion in Hong Kong. DESIGN. Retrospective study. SETTING. Three major acute
      hospitals and a specialised centre for joint replacement surgery with
      installation of an Operating Theatre Blood Transaction System. PATIENTS. Patients
      undergoing surgery under anaesthesia and requiring intra-operative transfusion
      for the period from the implementation of the system in individual institutes
      (Queen Elizabeth Hospital: June 1997; Princess Margaret Hospital: May 2001; Queen
      Mary Hospital: October 2009; and Hong Kong Buddhist Hospital: December 2010) till
      September 2011. RESULTS. Under the system, 58 923 units of red cells were
      released intra-operatively for 18 264 patients (11% of the total number of blood
      units issued by the blood banks in these institutes during the study period).
      About 1% of them (613 units) entailed unmatched red cells given to 183 patients
      for emergency transfusions during surgery. The mean time required for the issue
      of the first unit of red cells was less than 1 minute. A total of 1231 units of
      red cells were returned unused after being released. Among them, 95 units were
      deemed unfit for re-issue because they had left the temperature-monitored blood
      storage refrigerators in the operating theatres for more than 30 minutes. There
      was no delay in transfusion or postponement of surgery due to problems or
      downtime of the Operating Theatre Blood Transaction System. CONCLUSION. Our
      experience has shown that our virtual blood banking system was efficient and
      effective, and helped ensure that the right patient received the right amount of
      the right blood at the right time. The system can be implemented either locally
      in the same hospital with a central blood bank, or in a more remote and networked
      site without a nearby supporting blood bank.

PMID- 22865175
TI  - Relationship between population configuration and the spatial pattern of pandemic
      influenza A (H1N1) 2009 in Hong Kong.
AB  - OBJECTIVE. To investigate the association between population structure and the
      pandemic influenza A (H1N1) 2009 epidemic in a spatial context. DESIGN. A
      retrospective case-report series study. SETTING. Hong Kong. PATIENTS. Laboratory
      confirmed cases of human influenza A (H1N1) 2009 reported to the Centre for
      Health Protection between May and September 2009. MAIN OUTCOME MEASURES. A geo
      referenced database was established comprising age, gender, and residence
      location of all influenza A (H1N1) 2009 cases reported in the first 5 months of
      the Kong Kong epidemic's first wave in 2009. They were divided into four age
      categories: infant, student, adult, and elderly. Correlation coefficients and
      odds ratios were calculated to explore the association of H1N1 cases with
      population configurations in 400 District Council Constituency Areas. RESULTS. Of
      the 24 414 H1N1 cases reported, students accounted for the highest proportion
      (54.6%), followed by adults (33.4%), infants (11.1%), and the elderly (0.9%).
      Transmission was initially concentrated in students which then extended to
      infants and adults. Except for the elderly, the total population size and that of
      each age category were significantly associated with the H1N1 cases spatially.
      Mobility indicators as reflected by the number of students studying outside and
      adults working outside residential District Council Constituency Areas were also
      positively associated with H1N1 cases. CONCLUSIONS. Local population structure
      and mobility were associated with the spatial distribution of the H1N1 epidemic,
      despite the small size of the territory of Hong Kong. If an influenza epidemic
      hits again, an examination of these factors spatially would be useful in
      supporting the planning of interventions.

PMID- 22865176
TI  - Perceptions of professional attributes in medicine: a qualitative study in Hong
      Kong.
AB  - OBJECTIVE. Medical professionalism has been widely discussed in western scholarly
      literature. However, since Hong Kong has a mixed Chinese-western culture, it
      remains uncertain whether Hong Kong health care professionals, medical students,
      and patients see medical professionalism in exactly the same way as westerners.
      The objective of the present study was to explore perceptions of medical
      professionalism in Hong Kong. DESIGN. Individual semi-structured interviews.
      SETTING. Medical faculty preceptors, residents, interns, nurses, and students
      from the Li Ka Shing Faculty of Medicine of the University of Hong Kong. Subjects
      were recruited at an out-patient clinic of Queen Mary Hospital. PARTICIPANTS. We
      interviewed 39 subjects, including six medical faculty preceptors, six hospital
      residents, four medical interns, eight nurses, eight out-patients, and seven
      medical students. The interviews were transcribed and coded. Grounded theory was
      employed for framing and analysing the interviews. RESULTS. A total of 30 primary
      themes were identified and grouped under three secondary themes, ie 'Expectations
      of a professional doctor', 'Work values', and 'Patient care'. In general, the
      primary themes were consistent with recognised professional attributes in western
      bioethics, such as knowledge and skills, holistic care, and communication skills.
      A closer analysis suggested that traditional Chinese thought also played an
      important role in shaping the medical professionalism of Hong Kong. Challenges to
      be faced by Hong Kong doctors due to recent social changes were also identified.
      CONCLUSIONS. Medical professionalism in Hong Kong is shaped by both western
      medical ethics and traditional Chinese thought. The values treasured by Hong Kong
      health care professionals as well as technological advance, and the city's
      proximity to Mainland China makes Hong Kong health care unique. It is important
      to maintain the present work attitudes and at the same time adapt to new social
      changes.

PMID- 22865177
TI  - Clinical epidemiology workshop. Workshop 7--appraising a study on diagnosis.

PMID- 22865178
TI  - Diagnosing the cause of vertigo: a practical approach.
AB  - Dizziness is among the commonest of chief complaints. It often presents a
      significant challenge to the attending physician, because the symptoms and signs
      are often vague and non-specific. However, a robust systematic approach can
      usually arrive at the diagnosis. Maintaining balance requires sensory inputs from
      the vestibular, visual, and somatosensory systems and the cerebellum fine-tunes
      inaccurate motor outputs. Causes of vertigo are most commonly otological,
      followed by central, somatosensory, and visual. The first question in approaching
      patients with dizziness is to categorise dizziness into one of the four groups:
      lightheadedness, pre-syncope, disequilibrium, and vertigo. Secondly, central
      vertigo has to be differentiated with peripheral vertigo. For peripheral vertigo,
      the most common cause is benign paroxysmal positional vertigo and should be
      specifically looked for. The tempo of the vertiginous attacks and other
      associated symptoms can help differentiate the other causes of peripheral
      vertigo, including Meniere's disease, vestibular neuronitis, labyrinthitis, and a
      perilymph fistula.

PMID- 22865179
TI  - Ultrasound-guided thrombin injection for pseudoaneurysms: a case series at a
      local hospital.
AB  - Post-catheterization pseudoaneurysms are increasingly prevalent due to widespread
      use of endovascular procedures. Ultrasound-guided thrombin injection has emerged
      as a treatment of choice for these pseudoaneurysms. We review our experience
      performing this procedure for a series of cases from 2007 to 2010 with different
      clinical manifestations at a single hospital in Hong Kong. We achieved a high
      technical success rate with no complications.

PMID- 22865180
TI  - Hysterectomy for recurrent postmenopausal bleeding revisited: missed sclerosing
      stromal ovarian tumour.
AB  - Sclerosing stromal tumour of the ovary is rare. Patients present with menstrual
      irregularities, pelvic pain, abdominal distension, and presence of a large pelvic
      mass during their twenties or thirties. We report a rare case of an ovarian
      sclerosing stromal tumour with an atypical presentation, in that it gave rise to
      recurrent postmenopausal bleeding.

PMID- 22865181
TI  - Peanut aspiration: an avoidable life-threatening condition.
AB  - Foreign body aspiration is a potentially fatal condition. Yet, an accurate
      diagnosis may not be easy. Management is also challenging and requires a high
      level of expertise with proper instruments. In this article, we report our
      experience in the management of peanut aspiration in two young children by means
      of a ventilating bronchoscope.

PMID- 22865182
TI  - A rare neurological complication due to lithium poisoning.
AB  - Lithium salts have been used in treatment of depression and bipolar disorder for
      more than 50 years. Neurotoxic side-effects such as nystagmus, ataxia, tremor,
      fasciculation, clonus, seizure and even coma have been well described in the
      literature. We present a case of generalised peripheral neuropathy following
      lithium intoxication. It is a rare presentation with delayed onset and
      characterised by a rapid downhill course. Diagnosis was confirmed by nerve
      conduction tests, which showed axonal neuropathy. Despite the profound
      neurological effects of this toxicity, it is readily reversible with supportive
      care and the prognosis is good.

PMID- 22865183
TI  - An unusual cause for rings in the brain.
AB  - We report the case of a 35-year-old man from North India who presented with
      generalised tonic-clonic seizures and was found to have ring-enhancing brain
      lesions. He had a coincident adrenal mass lesion. Cultures from both regions grew
      Histoplasma capsulatum. He improved on treatment with itraconazole. This case is
      being reported since cerebral ring-enhancing lesions are rarely associated with
      histoplasmosis, and coincident adrenal involvement is also a rarity in an
      immunocompetent individual.

PMID- 22865184
TI  - Objectivity and fair assessment in the clinical viva: is it possible?

PMID- 22865185
TI  - Family violence accounts for 25% of homicides in Hong Kong.

PMID- 22865186
TI  - Alzheimer's disease biomarkers.

PMID- 22865187
TI  - Pneumococcus "die hard".

PMID- 22865188
TI  - Primary eosinophilic oesophagitis.

PMID- 22865189
TI  - Hydronephrosis associated with ureteral wall thickness: question.

PMID- 22865191
TI  - "Crawling-type" adenocarcinoma of the stomach: a distinct entity preceding poorly
      differentiated adenocarcinoma.
AB  - BACKGROUND: Gastric "crawling-type" adenocarcinoma (CTAC) is a neoplasm
      histologically comprising irregularly fused glands with low-grade cellular atypia
      that tends to spread laterally in the mucosa. It is necessary to elucidate the
      clinicopathological characteristics of CTAC. METHODS: We evaluated 25 CTACs-16
      intramucosal (M-) and 9 submucosal invasive (SM-) cancers-clinicopathologically
      and immunohistochemically. RESULTS: CTAC was most frequently located in the
      lesser curvature of the middle-third of the stomach. Macroscopically, 21 lesions
      were superficial-depressed and 4 were superficial-flat type. Histologically, all
      CTACs had cystic dilated glands and 16 lesions had focal signet-ring cells. All
      invasive areas of the SM-CTACs were occupied by poorly differentiated
      adenocarcinoma with an infiltrative growth pattern and abundant stroma. Fifteen
      CTACs were surrounded by mucosa with partial or no intestinal metaplasia. In the
      intramucosal area, 24 lesions were mixed phenotype with mucin and brush border
      immunoexpression. SM-CTAC was frequent in lesions with an intramucosal poorly
      differentiated component (PDC) greater than 10 mm in size (P = 0.041), and lymph
      node metastasis (LNM) was frequent in lesions with a PDC greater than 20 mm (P =
      0.039). The frequency of an expanded pattern (Ki-67-positive cells occupying > 50
      % of the mucosa) was higher in SM-CTAC than in M-CTAC (P = 0.027). p53
      overexpression was not detected in the intramucosal areas of any of the lesions.
      CONCLUSION: CTAC is a distinct subgroup of gastric adenocarcinoma in the early
      phase. A larger PDC and a Ki-67 expanded pattern were predictive of submucosal
      invasion or LNM.

PMID- 22865192
TI  - Sex-specific differences in the association between ABO genotype and gastric
      cancer risk in a Korean population.
AB  - BACKGROUND: Although previous studies have demonstrated an association between
      ABO blood group and the risk of gastric cancer (GC), only one study has
      identified these associations using the ABO genotype; however, that study did not
      evaluate sex differences in this association. The aim of the present study was to
      investigate whether there are sex-specific differences in the ABO genotype
      associated risk of GC. In addition, we explored the association of the ABO
      genotype and the clinicopathologic characteristics of GC in a Korean population.
      METHODS: We conducted a large-scale case-control study of 3245 GC patients (2204
      males, 1041 females) and 1700 controls (821 males, 879 females). The ABO genotype
      was determined by multicolor real-time polymerase chain reaction (PCR) using
      displacing probes. RESULTS: As compared with genotype OO, genotypes AA and AO in
      females, but not in males, were associated with a significantly increased risk of
      GC (odds ratio [OR] 1.56 and 95 % confidence interval [CI] 1.08-2.26 for AA; OR
      1.57 and 95 % CI 1.21-2.03 for AO). In a subgroup analysis, blood group A had a
      significantly increased risk of diffuse-type GC (OR 2.00, 95 % CI 1.43-2.78), but
      not of intestinal-type (OR 1.31, 95 % CI 0.96-1.79) or mixed-type GC (OR 1.43, 95
      % CI 0.92-2.24). CONCLUSION: The ABO genotypes AA and AO were significantly
      associated with GC only in females and only for diffuse-type GC. These data
      suggest that the association between ABO blood group and GC risk may differ
      according to sex and histological type.

PMID- 22865193
TI  - Effect of different gentamicin dose on the plasticity of the ribbon synapses in
      cochlear inner hair cells of C57BL/6J mice.
AB  - Faithful information transfer at the hair cell afferent synapse requires synaptic
      transmission to be both reliable and temporally precise. The release of
      neurotransmitter must exhibit both rapid on and off kinetics to accurately follow
      acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable
      temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on
      unique cellular and molecular specializations. To study effects of different
      doses of gentamicin on the changes of synaptic ribbons of cochlear inner hair
      cells (IHCs) in mice, the availability of genetic information, transgenic and
      knock-out animals make the C57BL/6J mouse a primary model in biomedical research.
      Aminoglycoside ototoxicity, however, has rarely been studied in mature mice
      because they are considered highly resistant to the drugs. This study presents
      models for gentamicin ototoxicity in adult C57BL/6J mouse strains. Five-week-old
      mice were injected intraperitoneally once daily with 50-300 mg gentamicin base/kg
      body weight for 7 days. Higher doses of gentamicin appear to be associated with
      earlier hearing damage in C57BL/6J mice, although not necessarily with more
      severe damage. At 200 mg/kg, gentamicin appears to induce significant hearing
      damage while not significantly affect the animal's general condition. Therefore,
      200 mg/kg may be an ideal dose for ototoxicity modeling in C57BL/6J mice using
      gentamicin. In the early period of different dose of gentamicin effect, when the
      number of hair cells had not changed, the number changes of IHC ribbon synapses
      had taken place. Through the number of ribbon synapses changing, IHCs increased
      or decreased connections with spiral ganglion nerves (SGNs). The ribbon synapses
      played a compensatory role for gentamicin ototoxicity, while this effect was not
      sufficient to maintain the normal threshold of hearing.

PMID- 22865194
TI  - Long-term results of laparoscopic Roux-en-Y Gastric bypass: evaluation after 9
      years.
AB  - This retrospective study aimed to evaluate the long-term results of the
      laparoscopic Roux-en-Y gastric bypass (LRYGB) procedure performed at our
      department of bariatric surgery. The 126 consecutive patients treated by LRYGB
      between January 1, 2001 and December 31, 2002 were analyzed in August 2011.
      Seventy-seven patients (61.1 %), including 18 who had had previous bariatric
      surgery, were available for evaluation after 9.4 +/- 0.6 years (range, 8.7-10.9
      years). Eight patients (10.4 %) suffered from type 2 diabetes mellitus (DMII) at
      the time of surgery. Initial body mass index (BMI) was 40.3 +/- 7.5 kg/m(2)
      (range, 24.5-66.1 kg/m(2)). There was no postoperative mortality, but two
      patients died of causes unrelated to the surgery. Some 9 % of the patients
      suffered from internal herniation, despite the closure of potential hernia sites.
      With time, the patients had the tendency to experience weight regain: percentage
      of excess BMI lost was 56.2 +/- 29.3 % (range, -78.8 to 117.9 %), down from a
      maximum of 88.0 +/- 29.6 % (range, -19.7 to 197.1 %), that had been obtained
      after a median of 2.0 years (range, 1-8 years). LRYGB was effective for diabetes
      control in 85.7 % of the affected patients, but, surprisingly, 27.9 % developed
      new-onset diabetes. The weight regain in this latter patient group was
      statistically not different from the nondiabetic group. Conversely, four patients
      required hospitalization for hypoglycemic syndrome. Two patients underwent
      reversal of their bypass for problems linked to glucose metabolism (one
      hypoglycemia, one DMII). Patient quality of life was fair. The patient
      satisfaction remained good in 76 % of the cases.

PMID- 22865196
TI  - Aerobic stability of distillers wet grains as influenced by temperature.
AB  - BACKGROUND: The storability of distillers wet grains (DWG) influences the
      economic, energetic, and carbon balances of fuel ethanol production, yet there
      are limited published data on the deterioration of DWG following its production.
      We used biogenic CO(2) production to assess the aerobic stability of DWG
      incubated at three temperatures (12  degrees C, 22  degrees C, 32  degrees C) and
      compared CO(2) production over time to the appearance of mold and changes in DWG
      color parameters. RESULTS: CO(2) production and mold colonization indicate that
      at temperatures near 12  degrees C, the aerobic stability of DWG was high and
      that it can be stored for at least a 10-day period. At temperatures close to 22 
      degrees C, the onset of increased microbial activity and visible mold
      colonization occurred between 4 and 7 days and both activity and mold ratings
      were very high by the ninth day in all three experiments. At 32  degrees C, 2
      days may be a more appropriate limit for storage. CONCLUSION: Temperature and
      time interact in a nonlinear fashion that permits the prediction of DWG stability
      boundaries. The simple visual appearance of mold appears to be a reasonable
      indicator that correlates well (r = 0.694) with CO(2) production, a measure of
      the aerobic stability of DWG.

PMID- 22865195
TI  - Selection and validation of suitable reference genes for miRNA expression
      normalization by quantitative RT-PCR in citrus somatic embryogenic and adult
      tissues.
AB  - miRNAs have recently been reported to modulate somatic embryogenesis (SE), a key
      pathway of plant regeneration in vitro. For expression level detection and
      subsequent function dissection of miRNAs in certain biological processes, qRT-PCR
      is one of the most effective and sensitive techniques, for which suitable
      reference gene selection is a prerequisite. In this study, three miRNAs and eight
      non-coding RNAs (ncRNA) were selected as reference candidates, and their
      expression stability was inspected in developing citrus SE tissues cultured at
      20, 25, and 30  degrees C. Stability of the eight non-miRNA ncRNAs was further
      validated in five adult tissues without temperature treatment. The best single
      reference gene for SE tissues was snoR14 or snoRD25, while for the adult tissues
      the best one was U4; although they were not as stable as the optimal multiple
      references snoR14 + U6 for SE tissues and snoR14 + U5 for adult tissues. For
      expression normalization of less abundant miRNAs in SE tissues, miR3954 was
      assessed as a viable reference. Single reference gene snoR14 outperformed
      multiple references for the overall SE and adult tissues. As one of the pioneer
      systematic studies on reference gene identification for plant miRNA
      normalization, this study benefits future exploration on miRNA function in citrus
      and provides valuable information for similar studies in other higher plants. KEY
      MESSAGE: Three miRNAs and eight non-coding RNAs were tested as reference
      candidates on developing citrus SE tissues. Best single references snoR14 or
      snoRD25 and optimal multiple references snoR14 + U6, snoR14 + U5 were identified.

PMID- 22865197
TI  - Remote sonographic interpretation: comparison of standardized video clips to
      still images.
AB  - OBJECTIVE: The aim of our study was to evaluate the role of standardized video
      clips compared with still images in the diagnostic accuracy of remote sonographic
      interpretation. METHODS: We compared the remote interpretation of sonographic
      examinations acquired with a standardized video clip approach to examinations
      performed with still images alone in 60 patients with various hepatic and
      extrahepatic pathologies. RESULTS: The use of video clips improved the diagnostic
      accuracy of sonographic studies interpreted remotely compared with the use of
      still images (p < 0.0001). The sensitivity, specificity, and positive and
      negative predictive values increased from 47.3% to 68.3%, 81.8% to 87.8%, 71.5%
      to 81%, and 63.8% to 74.5%, respectively. CONCLUSIONS: Standardized video clips
      are easy to obtain, less operator-dependent than still images, and can be
      transferred to remote sites without loss of important data. We recommend this
      method in remote interpretation (teleradiology and distant consultation) of
      sonographic examinations.

PMID- 22865198
TI  - Three-dimensional vascular mapping of the breast by using contrast-enhanced MRI:
      association of unilateral increased vascularity with ipsilateral breast cancer.
AB  - PURPOSE: We aimed to retrospectively compare three-dimensional vascular maps of
      both breasts obtained by dynamic magnetic resonance imaging (MRI) and determine
      the association of one-sided vascular prominence with ipsilateral breast cancer.
      MATERIALS AND METHODS: MRI was performed using gadolinium in 194 cases. Two
      readers scored vascular density using maximum intensity projections (MIPs).
      Dynamic fat-saturated T1-weighted gradientecho MIPs were acquired. Two readers
      evaluated the MIPs, and vessels greater than 2 mm in diameter and longer than 3
      cm were counted. The difference in vessel numbers detected in the two breasts
      determined the score. RESULTS: A total of 54 patients had malignant lesions
      (prevalence, 28%), including invasive ductal carcinoma (n=40), invasive mixed
      ductal-lobular carcinoma (n=5), invasive lobular carcinoma (n=3), ductal
      carcinoma in situ (n=3), mucinous carcinoma (n=1), medullary carcinoma (n=1), and
      leukemic metastasis (n=1). In 62 patients, there were benign lesions
      (fibroadenomas, fibrocysts), and four patients had inflammation (granulomatous
      mastitis in two patients, breast tuberculosis in two patients). There were 78
      normal cases. When a difference of at least two vessels was scored as vascular
      asymmetry, the sensitivity, specificity, positive likelihood ratio (+LR), and
      negative (-LR) of unilaterally increased vascularity associated with ipsilateral
      malignancy were 69%, 92%, 8.72, and 0.34, respectively. When four infection and
      three post-operative cases with vascular asymmetry were excluded; prevalence,
      specificity, and +LR increased to 29%, 97%, and 22.8, respectively, with the same
      sensitivity and -LR. Differences in mean vascularity scores were evaluated with
      regard to tumor size. T1 and T2 tumors were not significantly different from each
      other. The mean score of T3 tumors differed significantly from T1 and T2 tumors.
      CONCLUSION: MRI vascular mapping is an effective method for determining breast
      tissue vascularization. Ipsilateral increased vascularity was commonly associated
      with malignant breast lesions.

PMID- 22865200
TI  - Domain-specific trends in cognitive impairment after acute ischaemic stroke.
AB  - Little is known about the pattern of subacute cognitive domain impairments after
      ischaemic stroke, nor the temporal evolution of such impairments. Our objective
      was to investigate the pattern of cognitive impairment in different
      neuropsychological domains up to a year after ischaemic stroke. We included
      prospectively collected data from an observational database of stroke patients at
      the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
      Patients were categorised into temporal groups according to the time between the
      index stroke and neuropsychological profiling. The prevalence of impairment in
      different cognitive domains was then compared between these categories. The final
      cohort consisted of 209 patients. Frontal executive function, perceptual and
      nominal skills all showed a strong trend, with levels of impairment of
      approximately 30 % at <1 month and less than half this at >3 months (p < 0.05).
      Speed and attention was the most impaired domain, but had the greatest trend for
      decreasing impairment, from 72.4 % acutely to 37.9 % after 3 months (p < 0.01).
      By contrast, we found that impairment in visual and verbal memory showed no
      statistically significant change over time. Our results suggest a domain-specific
      improvement in cognition after ischaemic stroke. Early assessments may
      overestimate longer term cognitive deficits, particularly in speed and attention
      and perceptual functions. The domain-specific improvement patterns may help to
      inform long-term rehabilitation plans, which should not be based solely on
      cognitive assessments undertaken within the first month after stroke.

PMID- 22865199
TI  - LMI1195 PET imaging in evaluation of regional cardiac sympathetic denervation and
      its potential role in antiarrhythmic drug treatment.
AB  - PURPOSE: Regional cardiac sympathetic denervation (RCSD) associated with reduced
      noradrenaline transporter (NAT) function has been linked to cardiac arrhythmia.
      This study examined the association of LMI1195, an (18)F-labeled NAT substrate
      developed for positron emission tomography (PET) imaging, with NAT in vitro, and
      its imaging to detect RCSD and guide antiarrhythmic drug treatment in vivo.
      METHODS: LMI1195 association with NAT was assessed in comparison with other
      substrates, noradrenaline (NA) and (123)I-metaiodobenzylguanidine (MIBG), in NAT
      expressing cells. LMI1195 cardiac imaging was performed for evaluation of RCSD in
      a rabbit model surgically developed by regional phenol application on the left
      ventricular (LV) wall. The normal LV areas in images were quantified as regions
      with radioactivity >=50 % maximum. Potential impact of RCSD on dofetilide, an
      antiarrhythmic drug, induced ECG changes was assessed. RESULTS: NAT blockade with
      desipramine reduced LMI1195 cell uptake by 90 +/- 3 %, similar to NA and MIBG.
      NA, MIBG, or self inhibited LMI1195 cell uptake concentration-dependently with
      comparable IC(50) values (1.09, 0.21, and 0.90 MUM). LMI1195 cardiac imaging
      differentiated innervated and denervated areas in RCSD rabbits. The surgery
      resulted in a large denervated LV area at 2 weeks which was partially recovered
      at 12 weeks. Myocardial perfusion imaging with flurpiridaz F 18 showed normal
      perfusion in RCSD areas. Dofetilide induced more prominent QTc prolongation in
      RCSD than control animals. However, changes in heart rate were comparable.
      CONCLUSION: LMI1195 exhibits high association with NAT and can be used for
      imaging RCSD. The detected RCSD increases cardiac risks to the antiarrhythmic
      drug, dofetilide, by inducing more QTc prolongation.

PMID- 22865201
TI  - Resorcinarene-based cavitands with chiral amino acid substituents for chiral
      amine recognition.
AB  - Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (AMA),
      alanine undecyl resorcinarene acid (AUA) and glycine undecyl resorcinarene acid
      (GUA), which contain chiral amino acids, have been synthesized. The upper rim of
      the resorcinarene host is elongated with four identical substituents topped with
      alanine and glycine groups. The structures of the new resorcinarenes were
      elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the
      sustained off-resonance irradiation collision induced dissociation (SORI-CID)
      technique in FTICR-MS. These studies revealed that eight water molecules
      associate to the cavitand, two for each alanine group. The alanine substituent
      groups are proposed to form a kite-like structure around the resorcinarene
      scaffold. The binding of AMA, AUA, and GUA with chiral R- and S-methyl benzyl
      amines was studied by (1)H NMR titration, and compared to that of a binary L
      tartaric acid and the monoacid phthalyl alanine (PA). The results show that these
      compounds interact with amine guests; however, with four carboxylic acid groups,
      they bind several amine molecules strongly while the binary L-tartaric acid only
      binds one amine guest strongly. The simple compound PA, which contains one
      carboxylic group, shows weak binding to the amines. The (1)H NMR titration of AUA
      with primary, secondary, and tertiary chiral amines showed that it can
      discriminate between these three types of amines and showed chiral discrimination
      for chiral secondary amines.

PMID- 22865202
TI  - Cultural validation of the "use of intuition by nursing students scale - Turkish
      version".
AB  - PURPOSE: It is well known that intuition ability directly affects patient care
      quality and outcomes in nursing practice and is therefore an important aspect of
      nursing education. This study tests the validity and reliability of the Turkish
      version of the Scale of Use of Intuition by Nursing Students. DESIGN: The sample
      for this methodological study was composed of 250 nursing students. Each item of
      the scale was translated into Turkish by the researchers and validated for
      Turkish use. RESULTS: The item-total correlation was between .30 and .56 and its
      Cronbach alpha coefficient was .86. There was a statistically significant
      positive relationship between the level of clinical experience and the total
      points scored on the physical awareness, emotional awareness, and physical
      sensations subscales and from the total scale. CONCLUSIONS: Based on these
      results, the Turkish version of the Scale of Use of Intuition by Nursing Students
      is valid and reliable.

PMID- 22865203
TI  - Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice.
AB  - Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship
      with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric
      IgM are transported across the intestinal epithelium via the epithelial polymeric
      Ig receptor (pIgR) and provide a significant portion of the first line of natural
      or adaptive antibody-mediated immune defense of the intestinal mucosa. We found
      that colonic epithelial cells from pIgR KO mice differentially expressed (more
      than twofold change) more than 200 genes compared with cells from WT mice, and
      upregulated the expression of antimicrobial peptides in a commensal-dependent
      manner. Detailed profiling of microbial communities based on 16S rRNA genes
      revealed differences in the commensal microbiota between pIgR KO and WT mice.
      Furthermore, we found that pIgR KO mice showed increased susceptibility to
      dextran sulfate sodium-induced colitis, and that this was driven by their
      conventional intestinal microbiota. Thus, in the absence of pIgR, the stability
      of the commensal microbiota is disturbed, gut homeostasis is compromised, and the
      outcome of colitis is significantly worsened.

PMID- 22865204
TI  - Canadian Anesthesiologists' Society 2011 Royal College lecture: anesthesiology: a
      profession at a crossroads.

PMID- 22865206
TI  - Development of RT-LAMP and real-time RT-PCR assays for the rapid detection of the
      new duck Tembusu-like BYD virus.
AB  - A new duck Tembusu virus (TMUV), also known as BYD virus, has been identified as
      the causative agent for the emerging duck egg-drop syndrome in mainland China.
      The rapid spread and wide distribution of the new TMUV in mainland China result
      in heavy loss to the poultry industry and pose great threats to public health.
      Rapid and sensitive detection methods are critical for prevention and control of
      TMUV infections. In this study, a reverse-transcription loop-mediated isothermal
      amplification assay (RT-LAMP) and an SYBR Green-I-based real-time RT-PCR assay
      specific for the duck TMUV were developed and validated with laboratory and field
      samples, respectively. The detection limits were 1 * 10(-4) and 1 * 10(-3) PFU
      per reaction for the RT-LAMP assay and real-time RT-PCR assay, respectively. The
      specificities were analyzed with other related members of the genus Flavivirus,
      and no cross-reaction was observed. Furthermore, both assays were evaluated with
      field samples, and they exhibited high sensitivity and specificity. In addition,
      the real-time RT-PCR assay worked well in viral load analysis, which revealed
      that the spleen may be the primary target for the replication of new duck TMUV in
      ducks. The TMUV-specific RT-LAMP and real-time RT-PCR assays will provide useful
      tools for the diagnosis and epidemiological surveillance of TMUV infection.

PMID- 22865205
TI  - Biomarkers of sarcopenia in clinical trials-recommendations from the
      International Working Group on Sarcopenia.
AB  - Sarcopenia, the age-related skeletal muscle decline, is associated with relevant
      clinical and socioeconomic negative outcomes in older persons. The study of this
      phenomenon and the development of preventive/therapeutic strategies represent
      public health priorities. The present document reports the results of a recent
      meeting of the International Working Group on Sarcopenia (a task force consisting
      of geriatricians and scientists from academia and industry) held on June 7-8,
      2011 in Toulouse (France). The meeting was specifically focused at gaining
      knowledge on the currently available biomarkers (functional, biological, or
      imaging-related) that could be utilized in clinical trials of sarcopenia and
      considered the most reliable and promising to evaluate age-related modifications
      of skeletal muscle. Specific recommendations about the assessment of aging
      skeletal muscle in older people and the optimal methodological design of studies
      on sarcopenia were also discussed and finalized. Although the study of skeletal
      muscle decline is still in a very preliminary phase, the potential great benefits
      derived from a better understanding and treatment of this condition should
      encourage research on sarcopenia. However, the reasonable uncertainties (derived
      from exploring a novel field and the exponential acceleration of scientific
      progress) require the adoption of a cautious and comprehensive approach to the
      subject.

PMID- 22865207
TI  - Bladder augmentation and urinary diversion for neurogenic LUTS: current
      indications.
AB  - Augmentation cystoplasty and urinary diversion are no longer commonplace in the
      management of patients with neurogenic bladder, but remain an important surgical
      treatment for those with refractory LUTS who have failed neuromodulation and
      onabotulinum toxin treatment or who are not candidates for those treatments.
      Augmentation is an option in patients who can perform intermittent
      catheterization and is usually performed with ileum or large intestine. Some
      patients benefit from continent cutaneous catherizable channels. Supravesical
      urinary diversion may be necessary in more severe cases. Ileovesicostomies are
      being supplanted by indwelling suprapubic catheters, and when catheters fail
      conduits may be a better option. When feasible, the diverted bladder should be
      excised to avoid pyocystis.

PMID- 22865208
TI  - The role of neuromodulation in patients with neurogenic overactive bladder.
AB  - To review the treatment options for patients with neurogenic overactive bladder
      (OAB), specifically the use of sacral neuromodulation (SNM). A search was
      performed on the available literature on SNM and lower urinary tract dysfunction.
      Based on published studies available and also on personal experience, the
      treatment options for neurogenic OAB are reviewed, and specifically, the role for
      SNM in these patients is discussed. SNM is FDA-approved for patients with urge
      incontinence, urgency/frequency, and non-obstructive urinary retention. It
      involves stimulation of the third sacral nerve with an electrode implanted in the
      sacral foramen and connected to a pulse generator. The procedure is minimally
      invasive and is effective in about 70 % of patients who have a permanent system.
      The original trials leading to the approval of SNM excluded patients with
      neurogenic disease, as it was felt that intact spinal pathways were necessary for
      neuromodulation to occur. However, similar success rates have been observed in
      patients with neurogenic OAB. Special considerations for SNM use in patients with
      neurogenic OAB include recognizing that it is incompatible for patients who will
      need MRI's due to their progressive neurologic disease. Many treatment options
      are available for patients with neurogenic OAB. First-line approaches remain
      conservative with lifestyle changes and anticholinergic medications. SNM has been
      used successfully in this patient population with good results, though larger
      randomized trials are lacking.

PMID- 22865209
TI  - Dorsal genital nerve stimulation in patients with detrusor overactivity: a
      systematic review.
AB  - This study evaluates the outcome of trials to stimulate the dorsal genital nerve
      (DGN) in patients with lower urinary tract dysfunction. The aim of most studies
      was to suppress detrusor overactivity in patients with overactive bladder (OAB)
      syndrome by DGN stimulation. A literature search was performed using Pub Med, Web
      of Science, and Scopus databases (1980 to April 2012) for clinical trials of DGN
      stimulation in patients with detrusor overactivity. Seventeen studies were found
      in the literature. In the studies, different patterns of DGN stimulation were
      applied. The patterns were either continuous, conditional, or semi-conditional;
      on an acute or on a chronic basis. DGN stimulation lead to improvement of bladder
      capacity and reduction in urgency and/or incontinence episodes in many patients.
      The outcomes of conditional stimulation were comparable to continuous stimulation
      with respect to improvement of bladder capacity. The publications give evidence
      that DGN stimulation increases bladder capacity and suppresses involuntary
      detrusor contractions. Implantable DGN stimulation electrodes can open the way
      for more prolonged studies in larger patient groups to assess the effectiveness
      of chronic DGN stimulation in patients with OAB syndrome. Chronic DGN stimulation
      seems to be of value in the management of OAB syndrome.

PMID- 22865210
TI  - Analysis of a deep transcriptome from the mantle tissue of Patella vulgata
      Linnaeus (Mollusca: Gastropoda: Patellidae) reveals candidate biomineralising
      genes.
AB  - The gastropod Patella vulgata is abundant on rocky shores in Northern Europe and
      a significant grazer of intertidal algae. Here we report the application of
      Illumina sequencing to develop a transcriptome from the adult mantle tissue of P.
      vulgata. We obtained 47,237,104 paired-end reads of 51 bp, trialled de novo
      assembly methods and settled on the additive multiple K method followed by
      redundancy removal as resulting in the most comprehensive assembly. This yielded
      29,489 contigs of at least 500 bp in length. We then used three methods to search
      for candidate genes relevant to biomineralisation: searches via BLAST and Hidden
      Markov Models for homologues of biomineralising genes from other molluscs,
      searches for predicted proteins containing tandem repeats and searches for
      secreted proteins that lacked a transmembrane domain. From the results of these
      searches we selected 15 contigs for verification by RT-PCR, of which 14 were
      successfully amplified and cloned. These included homologues of Pif-177/BSMP,
      Perlustrin, SPARC, AP24, Follistatin-like and Carbonic anhydrase, as well as
      three containing extensive G-X-Y repeats as found in nacrein. We selected two for
      further verification by in situ hybridisation, demonstrating expression in the
      larval shell field. We conclude that de novo assembly of Illumina data offers a
      cheap and rapid route to a predicted transcriptome that can be used as a resource
      for further biological study.

PMID- 22865211
TI  - The impact of psychological symptoms on return to work in workers after
      occupational injury.
AB  - INTRODUCTION: This study aimed to investigate the impact of psychological
      symptoms on return to work (RTW) in workers after occupational injuries. METHODS:
      Our study candidates were injured workers who were hospitalized for 3 days or
      longer and received hospitalization benefits from the Labor Insurance. A self
      reported questionnaire including Brief Symptom Rating Scale (BSRS-50) and RTW was
      sent to workers at 12 weeks after injury. At 1 year, all participants were
      contacted again to determine whether or not they had RTW. RESULTS: A total of
      2001 workers completed the questionnaire (response rate 45.5 %) at 12 weeks after
      injury, among them, 1,149 had returned to work. Among the 852 who were unable to
      return to work at 12 weeks after injury, 225 reportedly returned to work by 1
      year. A proportional hazards regression indicated that after adjusting for all
      possible risk factors, higher scores in BSRS-50 and BSRS-5 at 12 weeks after
      injury were significant risk factors for not return to work (NRTW) at 1 year
      after injury. Other risk factors were gender, education level, length of
      hospitalization, affected physical appearance, and injury type. Among 10 psycho
      physiological symptoms of BSRS-50, a proportional hazards regression indicated
      that high score in phobic-anxiety scale was a risk factor for NRTW. CONCLUSIONS:
      After considering all other factors, psychological symptoms further predicted
      poorer probability of returning to work after occupational injury, and phobic
      anxiety was the most significant symptom predicting poor RTW. Development of
      preventive measures among injured workers according to the risk factors
      identified in this study is warranted.

PMID- 22865213
TI  - Health and Health Services Research Fund: Research Fund for the Control of
      Infectious Diseases: Research Dissemination Reports. Editorial.

PMID- 22865212
TI  - Effects of transfer of embryos independently cultured in essential and sequential
      culture media on pregnancy rates in assisted reproduction cycles.
AB  - PURPOSE: Several culture media are available to be used in ART. However it is
      uncertain whether embryos would preferably benefit from one type of medium or the
      association of different media. METHODS: We performed this study to evaluate the
      impact of simultaneous transfer of embryos independently cultured in two distinct
      culture media, on pregnancy outcome. A total of 722 couples who underwent
      infertility treatment were sequentially allocated into three groups: those who
      had half of the embryos individually cultured in MEM and the other half cultured
      in sequential media (MEM + Seq Group) (n = 243); those who had all embryos
      cultured only in sequential medium (Seq Group) (n = 239); and those who had all
      embryos cultured only in MEM (MEM Group) (n = 240). RESULTS: The pregnancy rate
      was higher in the MEM + Seq group (51.8 %) than the Seq group (36.7 %) (p <
      0.001). However the pregnancy rate observed in the MEM group was similar to the
      others (44.2 %). When a logistic regression test was applied it demonstrated that
      the number of transferred embryos did not interfere in the pregnancy rates.
      CONCLUSIONS: Our results suggests that offering different culture conditions for
      sibling embryos with subsequent transfer of embryos that were kept in distinct
      culture media, might increase pregnancy rates in assisted reproduction cycles.

PMID- 22865214
TI  - Smoking reduction intervention for smokers not willing to quit smoking: a
      randomised controlled trial.

PMID- 22865215
TI  - Prevalence of chronic pain, insomnia, and fatigue in Hong Kong.

PMID- 22865216
TI  - Neck pain in Hong Kong: a telephone survey on consequences and health service
      utilisation.

PMID- 22865217
TI  - Impact of SARS-coronavirus-encoded proteins on cellular signalling pathways and
      cytokine/chemokine gene expression.

PMID- 22865218
TI  - Neuroprotection in steroid therapy: a rodent model.

PMID- 22865219
TI  - Mental health impact of severe acute respiratory syndrome: a prospective study.

PMID- 22865220
TI  - Role of dendritic cells in SARS coronavirus infection.

PMID- 22865221
TI  - Detection of body temperature with infrared thermography: accuracy in detection
      of fever.

PMID- 22865222
TI  - Characterisation of animal angiotensin-converting enzyme 2 receptors and use of
      pseudotyped virus to correlate receptor binding with susceptibility of SARS-CoV
      infection.

PMID- 22865223
TI  - Voluntary counselling and testing plus information distribution to reduce HIV
      related risk behaviours among Hong Kong male cross-border truck drivers: a
      randomised controlled study.

PMID- 22865224
TI  - Prevalence and risk factors of sexually transmitted infections in female sex
      workers in Hong Kong.

PMID- 22865225
TI  - Characterisation of urinary stones in the presence of iodinated contrast medium
      using dual-energy CT: a phantom study.
AB  - OBJECTIVE: To develop a dual-energy CT (DECT) method for differentiating uric
      acid (UA) from non-UA stones in the presence of iodinated contrast medium.
      METHODS: Thirty UA and 45 non-UA stones were selected after infra-red
      spectroscopic analysis and independently placed in a 1.5-ml vial, which was
      filled first with saline and then with increasing concentrations of iodine. For
      each condition, tubes were put in a 35-cm water phantom and examined using a dual
      source CT system at 100 and 140 kV. Virtual unenhanced images created from CT
      data sets of the stones in iodine-containing solutions provided position and
      volume information. This map was used to calculate a CT number ratio to
      differentiate stone type. A region-growing method was developed to improve the
      ability to differentiate between UA and non-UA stones with iodinated contrast
      medium. RESULTS: The sensitivity for detecting UA stones was 100 % for unenhanced
      images but fell to 18 % with 20 mgI/ml iodine solution and 0 % for higher
      concentrations. With region growing, the sensitivity for detecting UA stones was
      increased to 100 %, 82 %, 57 %, 50 % and 21 % for iodine solutions of 20, 40, 60,
      80 and 100 mgI/ml. CONCLUSION: The region-growing method improves differentiation
      of UA from non-UA stones on contrast-enhanced DECT urograms. KEY POINTS: Computed
      tomography is widely used to assess renal tract calculi. Dual-energy CT can
      assess stone composition and provide virtual unenhanced images. However,
      iodinated contrast medium affects the volume estimation for urinary stones. CTR
      of stones is altered by the surrounding iodine in CT urograms. The region-growing
      method improves the identification of uric acid stones.

PMID- 22865226
TI  - Image registration improves human knee cartilage T1 mapping with delayed
      gadolinium-enhanced MRI of cartilage (dGEMRIC).
AB  - OBJECTIVES: To evaluate the effect of automated registration in delayed
      gadolinium-enhanced MRI of cartilage (dGEMRIC) of the knee on the occurrence of
      movement artefacts on the T1 map and the reproducibility of region-of-interest
      (ROI)-based measurements. METHODS: Eleven patients with early-stage knee
      osteoarthritis and ten healthy controls underwent dGEMRIC twice at 3 T. Controls
      underwent unenhanced imaging. ROIs were manually drawn on the femoral and tibial
      cartilage. T1 calculation was performed with and without registration of the T1
      weighted images. Automated three-dimensional rigid registration was performed on
      the femur and tibia cartilage separately. Registration quality was evaluated
      using the square root Cramer-Rao lower bound (CRLB(sigma)). Additionally, the
      reproducibility of dGEMRIC was assessed by comparing automated registration with
      manual slice-matching. RESULTS: Automated registration of the T1-weighted images
      improved the T1 maps as the 90% percentile of the CRLB(sigma) was significantly
      (P < 0.05) reduced with a median reduction of 55.8 ms (patients) and 112.9 ms
      (controls). Manual matching and automated registration of the re-imaged T1 map
      gave comparable intraclass correlation coefficients of respectively 0.89/0.90
      (patients) and 0.85/0.85 (controls). CONCLUSIONS: Registration in dGEMRIC reduces
      movement artefacts on T1 maps and provides a good alternative to manual slice
      matching in longitudinal studies.

PMID- 22865227
TI  - T1rho and T2 relaxation times for lumbar disc degeneration: an in vivo
      comparative study at 3.0-Tesla MRI.
AB  - OBJECTIVE: To determine the relative performance of T1rho and T2 relaxation times
      in disc degeneration assessment. METHODS: Lumbar sagittal MRI was performed at 3
      T in 52 subjects. With a spin-lock frequency of 500 Hz, T1rho was measured using
      a rotary echo spin-lock pulse embedded in a three-dimensional (3D) balanced fast
      field echo sequence. A multi-echo TSE sequence was used for T2 mapping. Regions
      of interest (ROIs) were drawn over the T1rho and T2 maps, including nucleus
      pulposus (NP) and annulus fibrosus (AF). Eight- and five-level disc degeneration
      semi-quantitative grading was performed. RESULTS: For NP, T1rho and T2 decreased
      quadratically with disc degeneration grades and had no significant trend
      difference (P = 0.40). For AF, T1rho decreased linearly as the disc degenerated
      and had a slope of -3.02 and -4.56 for eight- and five-level gradings
      respectively; while the slopes for T2 values were -1.43 and -1.84 respectively,
      being significantly flatter than those of T1rho (P < 0.001). There was no
      significant difference in T1rho and T2 values for both NP and AF among discs of
      grade 5/8 to 8/8 degeneration. CONCLUSION: T1rho is better suited for evaluating
      AF in degenerated disc than T2. In NP, T1rho and T2 decrease in a similar pattern
      following disc degeneration.

PMID- 22865228
TI  - Matrix production and collagen structure are enhanced in two types of osteogenic
      progenitor cells by a simple fluid shear stress stimulus.
AB  - Mesenchymal progenitor cells play a vital role in bone regenerative medicine and
      tissue engineering strategies. To be clinically useful osteoprogenitors should be
      readily available with the potential to form bone matrix. While mesenchymal
      stromal cells from bone marrow have shown promise for tissue engineering, they
      are obtained in small numbers and there is risk of donor site morbidity.
      Osteogenic progenitor cells derived from dermal tissue may provide a more
      abundant and easily expandable source of cells. Bone turnover in vivo is
      regulated by mechanical forces, particularly oscillatory fluid shear stresses
      (FSS), and in vitro osteogenic progenitors have been shown to be regulated by
      mechanical stimuli. The aim of this study was to assess what effect osteogenic
      media and FSS, generated by a simple rocking platform, had on cell behaviour and
      matrix production in human progenitor dermal fibroblasts (HDFs) and the embryonic
      stem cell-derived mesenchymal progenitor cell line (hES-MP). Osteogenic media
      stimulated alkaline phosphatase activity (ALP) and calcium deposition in HDFs.
      The addition of FSS further enhanced ALP activity and mineralised matrix
      deposition in both progenitor cells cultured in osteogenic media. Both types of
      progenitor cell subjected to FSS showed increases in collagen secretion and
      apparent collagen organisation as imaged by second harmonic generation.

PMID- 22865229
TI  - Deacetylation of C/EBPbeta is required for IL-4-induced arginase-1 expression in
      murine macrophages.
AB  - The amount of arginine available at inflammatory loci is a limiting factor for
      the growth of several cells of the immune system. IL-4-induced activation of
      macrophages produced arginase-1, which converts arginine into ornithine, a
      precursor of polyamines and proline. Trichostatin A (TSA), a pan-inhibitor of
      histone deacetylases (HDACs), inhibited IL-4-induced arginase-1 expression. TSA
      showed promoter-specific effects on the IL-4-responsive genes. While TSA
      inhibited the expression of arginase-1, fizz1, and mrc1, other genes, such as
      ym,1 mgl1, and mgl2, were not affected. The inhibition of arginase-1 occurred at
      the transcriptional level with the inhibition of polymerase II binding to the
      promoter. IL-4 induced STAT6 phosphorylation and binding to DNA. These activities
      were not affected by TSA treatment. However, TSA inhibited C/EBPbeta DNA binding.
      This inhibitor induced acetylation on lysine residues 215-216, which are critical
      for DNA binding. Finally, using macrophages from STAT6 KO mice we showed that
      STAT6 is required for the DNA binding of C/EBPbeta. These results demonstrate
      that the acetylation/deacetylation balance strongly influences the expression of
      arginase-1, a gene of alternative activation of macrophages. These findings also
      provide a molecular mechanism to explain the control of gene expression through
      deacetylase activity.

PMID- 22865230
TI  - Physician in triage improves emergency department patient throughput.
AB  - To determine if a physician in triage (PIT) improves Emergency Department (ED)
      patient flow in a community teaching hospital. This is an interventional study
      comparing patient flow parameters for the 3-month periods before and after
      implementation of a PIT model. During the interventional time an additional
      attending physician was assigned to triage from 1 p.m. to 9 p.m. daily. Outcome
      measures were median time to attending physician evaluation, median length of
      stay (LOS), number of patients who left without being seen (LWBS), and total time
      and number of days on ambulance diversion. Non-normally distributed values were
      compared with the Wilcoxon rank sum test. Proportions were compared with Chi
      square test. Outcome measures were available for 17,631 patients, of whom 8,620
      were seen before the initiation of PIT, and 9,011 were seen after PIT was
      implemented. For all patients, the median time from registration to attending
      physician evaluation was reduced by 36 min (1:41 to 1:05, p < 0.01) while the
      median LOS for all patients was reduced by 12 min (3:51 to 3:39, p < 0.01) after
      the intervention. Both the number of days on diversion (24 vs. 9 days) and total
      time on diversion (68 h 25 min vs. 26 h 7 min) were decreased, p < 0.01. Finally,
      there was a slight reduction in the number of patients who LWBS from 1.5 to 1.3
      %, but this was not statistically significant (p = 0.36). Patient flow parameters
      in a community teaching hospital were modestly improved as a result of PIT
      implementation.

PMID- 22865232
TI  - AIF depletion provides neuroprotection through a preconditioning effect.
AB  - Previous studies established a major role for apoptosis inducing factor (AIF) in
      neuronal cell death after acute brain injury. For example, AIF translocation from
      mitochondria to the nucleus determined delayed neuronal death, whereas reduced
      AIF expression provided neuroprotective effects in models of cerebral ischemia or
      brain trauma. The question remains, however, why reduced AIF levels are
      sufficient to mediate neuroprotection, since only very little AIF translocation
      to the nucleus is required for induction of cell death. Thus, the present study
      addresses the question, whether AIF gene silencing affects intrinsic death
      pathways upstream of nuclear translocation at the level of the mitochondria.
      Using MTT assays and real-time cell impedance measurements we confirmed the
      protective effect of AIF siRNA against glutamate toxicity in immortalized mouse
      hippocampal HT-22 neurons. Further, AIF siRNA prevented glutamate-induced
      mitochondrial fragmentation and loss of mitochondrial membrane potential. The
      protection of mitochondrial integrity was associated with preserved ATP levels,
      attenuated increases in lipid peroxidation and reduced complex I expression
      levels. Notably, low concentrations of the complex I inhibitor rotenone (20 nM),
      provided similar protective effects against glutamate toxicity at the
      mitochondrial level. These results expose a preconditioning effect as a mechanism
      for neuroprotection mediated by AIF depletion. In particular, they point out an
      association between mitochondrial complex I and AIF, which regulate each other's
      stability in mitochondria. Overall, these findings postulate that AIF depletion
      mediates a preconditioning effect protecting neuronal cells from subsequent
      glutamate toxicity through reduced levels of complex I protein.

PMID- 22865231
TI  - Inflammation, leukocytes and menstruation.
AB  - Menstruation has many of the features of an inflammatory process. The complexity
      and sequence of inflammatory-type events leading to the final tissue breakdown
      and bleeding are slowly being unravelled. Progesterone has anti-inflammatory
      properties, and its rapidly declining levels (along with those of estrogen) in
      the late secretory phase of each non-conception cycle, initiates a sequence of
      interdependent events of an inflammatory nature involving local inter-cellular
      interactions within the endometrium. Intracellular responses to loss of
      progesterone (in decidualized stromal, vascular and epithelial cells) lead to
      decreased prostaglandin metabolism and loss of protection from reactive oxygen
      species (ROS). Increased ROS results in release of NFkappaB from suppression with
      activation of target gene transcription and increased synthesis of pro
      inflammatory prostaglandins, cytokines, chemokines and matrix metalloproteinases
      (MMP). The resultant leukocyte recruitment, with changing phenotypes and
      activation, provide further degradative enzymes and MMP activators, which
      together with a hypoxic environment induced by prostaglandin actions, lead to the
      tissue breakdown and bleeding characteristic of menstruation. In parallel, at
      sites where shedding is complete, microenvironmentally-induced changes in
      phenotypes of neutrophils and macrophages from pro- to anti-inflammatory, in
      addition to induction of growth factors, contribute to the very rapid re
      epithelialization and restoration of tissue integrity.

PMID- 22865233
TI  - alpha5 beta1-integrins are sensors for tauroursodeoxycholic acid in hepatocytes.
AB  - Ursodeoxycholic acid, which in vivo is converted to its taurine conjugate
      tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic
      liver disease. Earlier work showed that TUDC exerts its choleretic properties in
      the perfused rat liver in an alpha5 beta1 integrin-mediated way. However, the
      molecular basis of TUDC-sensing in the liver is unknown. We herein show that TUDC
      (20 MUmol/L) induces in perfused rat liver and human HepG2 cells the rapid
      appearance of the active conformation of the beta1 subunit of alpha5 beta1
      integrins, followed by an activating phosphorylation of extracellular signal
      regulated kinases. TUDC-induced kinase activation was no longer observed after
      beta1 integrin knockdown in isolated rat hepatocytes or in the presence of an
      integrin-antagonistic hexapeptide in perfused rat liver. TUDC-induced beta1
      integrin activation occurred predominantly inside the hepatocyte and required
      TUDC uptake by way of the Na(+) /taurocholate cotransporting peptide. Molecular
      dynamics simulations of a 3D model of alpha5 beta1 integrin with TUDC bound
      revealed significant conformational changes within the head region that have been
      linked to integrin activation before. CONCLUSIONS: TUDC can directly activate
      intrahepatocytic beta1 integrins, which trigger signal transduction pathways
      toward choleresis. (HEPATOLOGY 2013).

PMID- 22865234
TI  - Imitation or innovation? Unselective mixed strategies can provide a better
      solution.
AB  - Current theory about the evolution of social learning in a changing environment
      predicts the emergence of mixed strategies that rely on some selective
      combination of social and asocial learning. However, the results of a recent
      tournament of social learning strategies [Rendell et al. Science 328(5975):208
      213, 2010] suggest that the success relies almost entirely on copying to learn
      behavior. Those authors conclude that mixed strategies are vulnerable to invasion
      by individuals using social learning strategies alone. Here we perform a
      competition using unselective strategies that differ only in the degree of social
      versus asocial learning. We show that, under the same conditions of the
      aforementioned tournament, a pure social learning strategy can be invaded by an
      unselectively mixed strategy and attain an equilibrium where the latter is
      majority. Although existing theory suggests that copying other individuals
      unselectively is not adaptive, we show that, at this equilibrium, the average
      individual fitness of the population is higher than for a population of pure
      asocial learners, overcoming Rogers' paradox in finite populations.

PMID- 22865236
TI  - Efficacy of the Pillar implant in the treatment of snoring and mild-to-moderate
      obstructive sleep apnea: a meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: The Pillar implant is one of the surgical options for
      snoring and obstructive sleep apnea (OSA). It is designed to be inserted into the
      soft palate to reduce vibration and collapsibility. The efficacy of the Pillar
      implant has been evaluated in various studies. However, only one study conducted
      a meta-analysis of the findings, and was based on only three studies. We tried to
      get a more definite conclusion on the efficacy of the Pillar implant. STUDY
      DESIGN: Meta-analysis. METHODS: Efficacies were analyzed separately, one for
      snoring and the other for mild-to-moderate OSA. We searched MEDLINE, LILACS,
      SCOPUS, and the Cochrane Library. The key words "snoring AND implants" were used
      for snoring, and "apnea AND implants" for OSA. Seven studies for snoring and
      seven studies for mild-to-moderate OSA were finally included for meta-analysis.
      For snoring patients, a visual analogue scale that is scored by the bed partner
      was used to evaluate the loudness of the snoring sound. RESULTS: The Pillar
      implant reduced snoring sound significantly (standardized mean difference [SMD], 
      0.591; 95% confidence interval [CI], -0.753 to -0.429, P < .001). For mild-to
      moderate OSA patients, the Pillar implant significantly reduced the Epworth
      Sleepiness Scale (SMD, -0.481; 95% CI, -0.606 to -0.358, P < .001), and apnea
      hypopnea index (SMD, -0.378; 95% CI, -0.619 to -0.138, P = .002). Mean extrusion
      rate was 9.3% (95% CI, 7.0 to 12.2%). CONCLUSIONS: The present results indicate
      that the Pillar implant has a moderate effect on snoring and mild-to-moderate
      OSA. However, we need more studies with high level of evidence to arrive at a
      definite conclusion.

PMID- 22865235
TI  - Anti-LFA-1 antibodies enhance metastasis of ocular lymphoma to the brain and
      contralateral eye.
AB  - Previously we demonstrated that intraperitoneal (IP) inoculation of Rev-2-T-6
      mouse lymphoma into syngeneic Balb/c hosts resulted in brain metastasis,
      migration along the optic nerve sheath, and ocular infiltration. In a second
      model: intravitreal inoculation of Rev-2-T-6 cells, the developing lymphoma was
      largely confined within the eye, seldom breaching the retinal pigment epithelium
      to reside in the choroid and sclera. There was no retrograde infiltration into
      the brain. Here, we describe a third, complementary model, whereby intravitreal
      inoculation of Rev-2-T-6 cells into Balb/c mice, followed by repeated IP
      inoculations of anti-LFA-1/CD11a monoclonal antibodies, results in extensive
      infiltration of the choroid, sclera, conjunctiva, eyelids and orbit. Furthermore,
      the lymphoma cells metastasize along the optic nerve sheath into the brain, and
      through the contralateral optic nerve tract into the contralateral eye. There is
      no systemic involvement of the lymphoma. Furthermore, anti-LFA-1 treatment
      results in elevated levels of serum anti-Rev-2-T-6 antibodies. Inoculation of Rev
      2-T-6 cells into the vitreous of severe combined immune deficient mice
      demonstrates a course of clinical signs and histopathological findings similar to
      those in immune-competent mice treated with anti-LFA-1 antibodies, including
      invasion of the contralateral eye. Taken together, these findings suggest that
      confinement of Rev-2-T-6 lymphoma cells to the eye depends on active immune
      surveillance using a population of effector cells expressing the cell surface
      integrin LFA-1. Impairing this protection enhances tumor aggressiveness within
      the eye, and the likelihood of early retrograde lymphoma metastasis into the
      brain and the contralateral eye.

PMID- 22865237
TI  - Antidepressant use is related to larger white matter lesion volume in patients
      with symptomatic atherosclerotic disease: the SMART-MR study.
AB  - Although a relation between depression and white matter lesions (WML) is
      frequently observed, the direction of causation remains unknown. We investigated
      whether depressed mood was associated with baseline severity and change in WML
      volume during 4 years of follow-up, and the relative contribution of mood
      symptoms and antidepressant use to this relation. Within the SMART-MR study 594
      patients (58 +/- 10 years) with symptomatic atherosclerotic disease had
      assessments of mood symptoms and antidepressant use and 1.5 T MRI at baseline and
      after 3.9 +/- 0.4 years of follow-up. Mood symptoms were assessed using the
      Mental Health Index (MHI-5). Depressed mood was defined as antidepressant use
      and/or MHI-5 score <= 52. Volumetric WML measures (deep and periventricular) were
      obtained with automated segmentation. Linear regression analyses were adjusted
      for age, sex, baseline WML volume, follow-up time, vascular risk factors and
      infarcts. Depressed mood was not associated with larger WML volume at baseline.
      However, when separate contributions were distinguished, antidepressant use was
      associated with greater deep (B = 0.50 mL, 95 % CI 0.04-0.96) and periventricular
      WML volume (B = 0.47 mL, 95 % CI 0.05-0.89) at baseline, while mood symptoms were
      not. Antidepressants were associated with a modest but non-significant increase
      in progression of periventricular WML volume over 4 years of follow-up (B = 0.21
      mL, 95 % CI -0.05 to 0.47). WML at baseline were not associated with new-onset
      depressed mood at follow-up. Antidepressants, but not mood symptoms, were
      associated with greater WML volume and a modest, although non-significant
      increase in periventricular WML volume in patients with symptomatic
      atherosclerotic disease. Future studies are needed to determine whether this may
      be a direct effect, or whether other underlying diseases for which
      antidepressants are prescribed influence this relation.

PMID- 22865238
TI  - Expanded and independent validation of the Movement Disorder Society-Unified
      Parkinson's Disease Rating Scale (MDS-UPDRS).
AB  - The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing
      satisfactory clinimetric results and has been proposed as the official benchmark
      scale for Parkinson's disease. The present study, based on the official MDS-UPDRS
      Spanish version, performed the first independent testing of the scale and adds
      information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS
      Spanish version showed a comparative fit index >= 0.90 for each part (I-IV)
      relative to the English-language version and was accepted as the Official MDS
      UPDRS Spanish version. Data from this scale, applied with other assessments to
      Spanish-speaking Parkinson's disease patients in five countries, were analyzed
      for an independent and complementary clinimetric evaluation. In total, 435
      patients were included. Missing data were negligible and moderate floor effect
      (30 %) was found for Part IV. Cronbach's alpha index ranged between 0.79 and 0.93
      and only five items did not reach the 0.30 threshold value of item-total
      correlation. Test-retest reliability was adequate with only two sub-scores of the
      item 3.17, Rest tremor amplitude, reaching kappa values lower than 0.60. The
      intraclass correlation coefficient was higher than 0.85 for the total score of
      each part. Correlation of the MDS-UPDRS parts with other measures for related
      constructs was high (>= 0.60) and the standard error of measurement lower than
      one-third baseline standard deviation for all subscales. Results confirm those of
      the original study and add information on scale reliability, construct validity,
      and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric
      characteristics.

PMID- 22865239
TI  - Management of right-to-left shunt in cryptogenic cerebrovascular disease: results
      from the observational Austrian paradoxical cerebral embolism trial (TACET)
      registry.
AB  - Paradoxical embolism due to a patent foramen ovale (PFO) is a possible cause of
      ischemic stroke, particularly in young cryptogenic stroke patients. In most
      cases, however, it is difficult to establish a firm etiological association and
      the debate about management is ongoing. The Austrian Paradoxical Cerebral
      Embolism Trial was designed as a prospective, national, multi-center, non
      randomized registry to add further data on this topic before the completion of
      randomized controlled trials. Over 27 months 188 cryptogenic stroke/TIA patients
      <=55 years were entered by 15 Austrian stroke units. Contrast transesophageal
      echocardiography demonstrated a cardiac right-to-left shunt (RLS) in 176
      patients; a pulmonary RLS was assumed in 10, and 2 showed both. Ninety-seven (55
      %) patients with cardiac RLS underwent interventional treatment, and this was
      more likely for patients with stroke as index event, a symptomatic infarction on
      MRI and a large size of PFO. Over 2 years, recurrences occurred at a rate of
      approximately 1.3 % for stroke and 4.3 % for TIA, and were especially frequent in
      patients with pulmonary RLS. When comparing outcomes in patients with cardiac RLS
      there was a trend for fewer recurrences with interventional management (closure:
      four TIA in four patients vs. medical: three strokes and seven TIA in nine
      patients; p = 0.066 for events, p = 0.085 for patients). The complication rate
      was 13.4, and 5.7 % had residual shunting. The possible causes for paradoxical
      embolism in young patients with cryptogenic stroke appear more variable than
      usually considered, and other causes than PFO should not be neglected.
      Interventional treatment of a cardiac RLS may offer a small benefit, but has to
      be weighed against possible complications and the problem of establishing
      causality.

PMID- 22865241
TI  - Perceptions of genetic research in three rural Appalachian Ohio communities.
AB  - Appalachian Americans are an underserved population with increased risk for
      diseases having strong genetic and environmental precursors. The purpose of this
      study is to understand the thoughts and perceptions of genetic research of
      Appalachian Americans residing in eastern Ohio prior to conducting a genetic
      research study with this population. A genetic survey was developed and completed
      by 180 participants from Marietta, Cambridge and East Liverpool, Ohio. The
      majority of respondents were Caucasian women with a median age of 37.5 years. We
      found that participants had a high interest in participating in 80 %, allowing
      their children to participate in 78 %, and learning more about genetic research
      studies (90 %); moreover, they thought that genetic research studies are useful
      to society (93 %). When asked what information would be useful when deciding to
      participate in a genetic research study, the following were most important: how
      environmental pollutants affect their genes and their child's genes (84 %), types
      of biological specimens needed for genetic research studies (75 %) and who will
      have access to their samples (75 %). Of the 20 % who responded that they were
      "unsure" about participating in a genetic research study, the leading reason was
      "I don't have enough information about genetic research to make a decision" (56
      %). We also asked respondents to choose their preferred method for receiving
      genetic information, and the principal response was to read a brochure (40 %).
      Findings from this study will improve community education materials and
      dissemination methods that are tailored for underserved populations engaged in
      genetic research.

PMID- 22865242
TI  - Reduction of sodium and increment of calcium and omega-3 polyunsaturated fatty
      acids in dry fermented sausages: effects on the mineral content, lipid profile
      and sensory quality.
AB  - BACKGROUND: A combined technological approach was applied in the development of
      healthier dry fermented sausages: a partial substitution of the pork back fat by
      pre-emulsified linseed oil and a partial replacement of sodium chloride with
      calcium ascorbate at two different levels, leading to low amounts of salt
      (14gSalt and 10gSalt, with 14 g and 10 g NaCl per kg of mixture, respectively).
      RESULTS: The developed products (14gSalt and 10gSalt) showed adequate results for
      a(w) (0.85 and 0.87) and pH (4.98 and 5.21), and low lipid oxidation values (1.4
      * 10(-4) and 1.5 * 10(-5) g malondialdehyde (MDA) kg(-1)). The lipid modification
      led to a significantly higher supply of omega-3 (23.3 g kg(-1) ) compared to the
      control (3.2 g kg(-1) ). Simultaneously, reductions of 38% and 50% in sodium
      content and a calcium supply of 4 and 5.2 g kg(-1) were achieved in the 14gSalt
      and 10gSalt formulations, respectively, compared to the control products (26 g
      salt and 0.87 g kg(-1) Ca). Instrumental analysis of colour and texture and
      sensory studies demonstrated that the organoleptic quality of the new
      formulations was similar to that of traditional products. CONCLUSIONS: The
      developed dry fermented sausages showed healthier properties than traditional
      ones owing to their reduced sodium and higher calcium content and a significant
      supply of omega-3 fatty acids.

PMID- 22865243
TI  - Characterization of the sporophyte-preferential gene promoter from the red alga
      Porphyra yezoensis using transient gene expression.
AB  - The life cycle of plants entails an alternation of generations, the diploid
      sporophyte and haploid gametophyte stages. There is little information about the
      characteristics of gene expression during each phase of marine macroalgae.
      Promoter analysis is a useful method for understanding transcriptional
      regulation; however, there is no report of promoter analyses in marine
      macroalgae. In this study, with the aim of elucidating the differences in the
      transcriptional regulatory mechanisms between the gametophyte and sporophyte
      stages in the marine red alga Porphyra yezoensis, we isolated the promoter from
      the sporophyte preferentially expressed gene PyKPA1, which encodes a sodium pump,
      and analyzed its promoter using a transient gene expression system with a
      synthetic beta-glucuronidase (PyGUS) reporter. The deletion of -1432 to -768
      relative to the transcription start site resulted in decreased GUS activity in
      sporophytes. In contrast, deletion from -767 to -527 increased GUS activity in
      gametophytes. Gain-of-function analyses showed that the -1432 to -760 region
      enhanced the GUS activity of a heterologous promoter in sporophytes, whereas the 
      767 to -510 region repressed it in gametophytes. Further mutation and gain-of
      function analyses of the -767 to -510 region revealed that a 20-bp GC-rich
      sequence (-633 to -614) is responsible for the gametophyte-specific repressed
      expression. These results showed that the sporophyte-specific positive regulatory
      region and gametophyte-specific negative regulatory sequence play a crucial role
      in the preferential expression of PyKPA1 in P. yezoensis sporophytes.

PMID- 22865244
TI  - Recommendations regarding dietary intake and caffeine and alcohol consumption in
      patients with cardiac arrhythmias: what do you tell your patients to do or not to
      do?
AB  - OPINION STATEMENT: The etiology of arrhythmias including atrial fibrillation is
      multifactorial. Most arrhythmias are associated with comorbid illnesses like
      hypertension, diabetes, thyroid disease, or advanced age. Although it is tempting
      to blame a stimulant like caffeine as a trigger for arrhythmias, the literature
      does not support this idea. There is no real benefit to having patients with
      arrhythmias limit their caffeine intake. Caffeine is a vasoactive substance that
      also may promote the release of norepinephrine and epinephrine. However, acute
      ingestion of caffeine (as coffee or tea) does not cause atrial fibrillation. Even
      patients suffering a myocardial infarction do not have an increased incidence of
      ventricular or other arrhythmias after ingesting several cups of coffee. Large
      epidemiologic studies have also failed to find a connection between the amount of
      coffee/caffeine used and the development of arrhythmias. As such, it does not
      make sense to suggest that patients with palpitations, paroxysmal atrial
      fibrillation, or supraventricular tachycardia, abstain from caffeine use. Energy
      drinks are a new phenomenon on the beverage market, with 30-50 % of young adults
      and teens using them regularly. Energy drinks are loaded with caffeine, sugar,
      and other chemicals that can stimulate the cardiac system. There is an increasing
      body of mainly anecdotal case reports describing arrhythmias or even sudden death
      triggered by exercise plus using energy drinks. Clearly, there must be more study
      in this area, but it is wise to either limit or avoid their use in patients with
      arrhythmias. Moderate to heavy alcohol use seems to be associated with the
      development of atrial fibrillation. The term "holiday heart" was coined back in
      1978, to describe patients who had atrial fibrillation following binge alcohol
      use. Thus, it is reasonable to recommend to patients with arrhythmias that they
      limit their alcohol use, although unfortunately this treatment will likely not
      completely resolve their arrhythmia.

PMID- 22865245
TI  - Updates on the inherited cardiac ion channelopathies: from cell to clinical.
AB  - OPINION STATEMENT: The inherited channelopathies are a rare, heterogeneous group
      of diseases with widely variable clinical presentations and courses. Systematic
      clinical and experimental work has led to identification of disease-causing
      genetic mutations and their biophysical manifestation. The process by which the
      knowledge base is developed, from genetic mutation, to cardiac myocyte, to whole
      heart, and finally to clinical presentation, has dramatically expanded our
      understanding of these diseases. Most importantly, we can now begin to comprehend
      how small changes at the genetic level can dramatically influence a patient's
      clinical course.

PMID- 22865246
TI  - Structure-function relationships in human D-amino acid oxidase.
AB  - Since D-amino acids were identified in mammals, D-serine has been one of the most
      extensively studied "unnatural amino acids". This brain-enriched transmitter-like
      molecule plays a pivotal role in the human central nervous system by modulating
      the activity of NMDA receptors. Physiological levels of D-serine are required for
      normal brain development and function; thus, any alterations in neuromodulator
      concentrations might result in NMDA receptor dysfunction, which is known to be
      involved in several pathological conditions, including neurodegeneration(s),
      epilepsy, schizophrenia, and bipolar disorder. In the brain, the concentration of
      D-serine stored in cells is defined by the activity of two enzymes: serine
      racemase (responsible for both the synthesis and degradation) and D-amino acid
      oxidase (which catalyzes D-serine degradation). Both enzymes emerged recently as
      new potential therapeutic targets for NMDA receptor-related diseases. In this
      review we have focused on human D-amino acid oxidase and provide an extensive
      overview of the biochemical and structural properties of this flavoprotein and
      their functional significance. Furthermore, we discuss the mechanisms involved in
      modulating enzyme activity and stability with the aim to substantiate the pivotal
      role of D-amino acid oxidase in brain D-serine metabolism in physiological and
      pathological conditions and to highlight its great significance for novel drug
      design/development.

PMID- 22865247
TI  - Amperometric microbiosensor as an alternative tool for investigation of D-serine
      in brain.
AB  - This paper discusses the application of a reagentless, selective microbiosensor
      as a useful alternative tool for monitoring D-serine in neural samples. The main
      components of the 125-MUm-diameter disk biosensor were D-amino acid oxidase for D
      serine sensitivity (linear region slope, 61 +/- 7 MUA cm(-2) mM(-1); limit of
      detection, 20 nM), and poly-phenylenediamine for rejection of electroactive
      interference. The response time of the biosensor was of the order of 1 s, ideal
      for 'real-time' monitoring, and detection of systemically administered D-serine
      in brain extracellular fluid is demonstrated. Exploitation of this probe might
      resolve queries involving regulation of D-serine in excitotoxicity, and
      modulation of N-methyl-D-aspartate receptor function by D-serine and glycine in
      the central nervous system.

PMID- 22865248
TI  - Amino acid sensing in the gastrointestinal tract.
AB  - Rapid progress in gastroenterology during the first part of the last century has
      shown that gastrointestinal (GI) function is regulated by neuroendocrine,
      paracrine and endocrine signals. However, recent advances in chemical sensing,
      especially in the last decade, have revealed that free L-amino acids (AA), among
      other nutrients, play a critical role in modifying exocrine and endocrine
      secretion, modulating protein digestion, metabolism and nutrient utilization, and
      supporting the integrity and defense of the GI mucosa. Many of the mechanisms by
      which AAs elicit these functions in the GI has been linked to the traditional
      concept of hormone release and nervous system activation. But most these effects
      are not direct. AAs appear to function by binding to a chemical communication
      system such as G protein-coupled receptors (GPCRs) that activate signaling
      pathways. These intracellular signals, although their molecular bases are not
      completely elucidated yet, are the ones responsible for the neuronal activity and
      release of hormones that in turn regulate GI functions. This review aims to
      describe the distribution of the known GPCRs from the class 3 superfamily that
      bind to different kinds of AA, especially from the oropharyngeal cavity to the
      stomach, what kind of taste qualities they elicit, such as umami, bitter or
      sweet, and their activity in the GI tract.

PMID- 22865249
TI  - Fusion protein strategy to increase expression and solubility of hypervariable
      region of VP2 protein of infectious bursal disease virus in Escherichia coli.
AB  - Infectious bursal disease is one of the most important viral diseases in the
      young chickens. VP2 protein is the major host protective immunogen of the virus.
      A hypervariable region is present in VP2 protein (hvVP2) that contains
      immunodominant epitops. The high hydrophobicity of hvVP2 region causes protein
      aggregation in Escherichia coli (E. coli). The objective of the present study was
      to improve the expression and the solubility of the hvVP2 protein in E. coli. The
      effects of fusion partners on the solubility of hvVP2 protein were studied. The
      protein was expressed in forms of unfused and N-terminally fused to GST and NusA.
      The results showed that the unfused hvVP2 protein was expressed in very low
      level. But, N-terminally fused hvVP2 protein to GST (glutathione-S-transferase)
      and NusA (N utilization substance A) showed significantly enhanced protein
      expression. The fusion of GST and hvVP2 was produced in aggregated form while in
      the presence of NusA, the hvVP2 protein was expressed in a soluble form. The NusA
      hvVP2 protein was detected by a neutralizing monoclonal antibody, 1A6, in antigen
      capture ELISA. In conclusion, the NusA protein is a suitable fusion partner to
      improve expression and solubility of the hvVP2 protein in E. coli.

PMID- 22865250
TI  - Iatrogenic false aneurysms. A rare complication of hip surgery.
AB  - The purpose of this study was to determine the incidence of arterial false
      aneurysms following hip surgery diagnosed and treated in our hospital between
      January 1995 and January 2010. We conducted a retrospective analysis of all
      patients undergoing hip surgery (osteosynthesis, hemiarthroplasty, total
      arthroplasty, or revision arthroplasty) under our care. To determine the
      incidence of arterial false aneurysm, we identified patients with abnormal
      bleeding through the surgical wound postoperatively. Out of the 11,839 patients
      undergoing hip surgery during the study period, 321 had abnormal bleeding that
      aroused suspicion of an associated vascular lesion. Among these, the presence of
      a false aneurysm requiring specific treatment was confirmed in eight patients.
      False aneurysms are a rare and occasionally severe complication of hip surgery
      that typically manifest with significant haemorrhage during the postoperative
      period. The management of these lesions by interventional radiology is associated
      with few complications and permits rapid patient stabilisation and early
      recovery, avoiding more aggressive and sometimes fruitless surgical exploration.

PMID- 22865251
TI  - Magnetic resonance arthrography for labral tears and chondral wear in
      femoroacetabular impingement.
AB  - Magnetic resonance arthrography (MRA) is a useful pre-operative investigation for
      patients with clinical signs and symptoms of femoroacetabular impingement. Our
      aim was to assess the diagnostic accuracy of MRA in detecting labral tears and
      chondral wear in this context. Sixty nine hips were included in the study after
      exclusions. All patients underwent pre-operative MRA and then subsequent hip
      arthroscopy. The findings at MRA were compared to those found intraoperatively.
      For labral tears, sensitivity, specificity and accuracy were 81%, 51% and 58%
      respectively. For chondral wear these figures were 17%, 100%, and 55%
      respectively. In our institution, MRA was therefore not as accurate as previously
      published work suggests.

PMID- 22865252
TI  - Femoral torsion: reliability and validity of the trochanteric prominence angle
      test.
AB  - Influence of femoral torsion on femoroacetabular impingement and other hip
      conditions is not well documented and its assessment by imaging methods during
      clinical work-up is not routinely performed. We studied whether physical
      examination could reliably measure or at least screen for gross anomalies of
      femoral torsion or if appropriate imaging should routinely be performed.
      Assessing femoral torsion of 45 volunteers using the "trochanteric prominence
      angle test" and magnetic resonance imaging (MRI), inter- and intra-observer
      reliability ranged from poor to moderate and agreement with MRI values was only
      fair. Considering a 5 degrees  to 10 degrees  difference of femoral torsion as
      clinically relevant, physical examination failed to match MRI values within +/-10
      degrees  in more than 50%. Arbitrarily defining thresholds for pathological
      femoral torsion, the "trochanteric prominence angle test" could not recognise
      torsions outside the >30 degrees /<0 degrees  range and diagnosed torsions
      outside the >20 degrees /<10 degrees  range with a sensitivity of 18%-75% and a
      specificity of 58%-98% only. Physical assessment of femoral torsion using the
      "trochanteric prominence angle test" does not allow reliable measurement or
      screening for gross anomalies. We therefore integrate an adapted MRI protocol
      allowing measurement of femoral torsion within our clinical work up.

PMID- 22865253
TI  - Do we medialise the hip centre of rotation in total hip arthroplasty? Influence
      of acetabular offset and surgical technique.
AB  - Acetabular offset (AO) is the distance between the centre of the femoral head and
      the true floor of the acetabulum. We quantified the AO in normal hips and
      compared the displacement of the centre of rotation of the hip (CRH) after
      conventional and anatomical cup implantation during THA. 100 CT-scans of normal
      hips were analysed before and after simulating implantation of the acetabular
      component. Mean AO was 30.8 mm +/- 3.The medial shift of the CRH was 1.6 mm +/-
      1.2 with the anatomical and 4.8 mm +/- 1.9 with the conventional technique
      (p<0.0001). Medialisation was greater than 5 mm in 44% of the cases when the
      conventional technique was used, but occurred in no case when using the
      anatomical technique. Differences between men and women were significant: 5.6 mm
      +/- 1.6 and 3.5 mm +/- 1.7 with the conventional technique; 2.0 mm +/- 1.1 and
      0.9 mm +/- 0.9 with the anatomical technique (p<0.0001 for both measurements).
      The concept of hip offset cannot be limited to that of the femoral offset. AO
      widely varies and cannot be neglected. In patients with significant AO, surgeons
      should pay close attention to the preparation of the acetabulum. This should be
      done conservatively so that the acetabular cup can be placed anatomically in
      order to restore the native hip biomechanics.

PMID- 22865254
TI  - The articular surface replacement implant recall: a United Kingdom district
      hospital experience.
AB  - We present our experience of the articular surface replacement (ASR) hip and the
      implant recall process. One hundred and twenty-one ASR components were implanted
      (21 resurfacing hip arthroplasty (RHA) and 100 ASR/XL modular total hip
      replacements). At the time of the implant recall in August 2010 there were 111
      surviving hips (92%) with a mean follow-up of 44 months. Nine hips had been
      revised and one had been listed for revision surgery. Ninety-two percent of
      surviving implants were reviewed in the recall clinics, and blood metal ion
      levels or ultrasound scans were indicated in 38 hips (34%). Immediately after the
      recall process seven hips (6 ASR/XL and 1 RHA) were listed for revision and a
      further 9 were kept under close surveillance. One year after completion of the
      recall process 23 hips (19 ASR/XL and 4 RHA's) had been revised. A diagnosis of
      adverse reaction to metal debris (ARMD) was made at surgery in all but two hips.
      Our current revision rate for ASR RHA is 19% (mean follow-up 62 months, range 29
      80) and for the ASR/XL is 19% (mean follow-up 53 months, range 10-80). The 5-year
      cumulative survival rates with revision for any reason for the ASR/XL, was 80.8%
      (95% confidence interval 72.0 - 89.5). Given experience elsewhere we expect this
      rate may increase significantly with time.

PMID- 22865255
TI  - Using halogen bonds to address the protein backbone: a systematic evaluation.
AB  - Halogen bonds are specific embodiments of the sigma hole bonding paradigm. They
      represent directional interactions between the halogens chlorine, bromine, or
      iodine and an electron donor as binding partner. Using quantum chemical
      calculations at the MP2 level, we systematically explore how they can be used in
      molecular design to address the omnipresent carbonyls of the protein backbone. We
      characterize energetics and directionality and elucidate their spatial
      variability in sub-optimal geometries that are expected to occur in protein
      ligand complexes featuring a multitude of concomitant interactions. By deriving
      simple rules, we aid medicinal chemists and chemical biologists in easily
      exploiting them for scaffold decoration and design. Our work shows that carbonyl
      halogen bonds may be used to expand the patentable medicinal chemistry space,
      redefining halogens as key features. Furthermore, this data will be useful for
      implementing halogen bonds into pharmacophore models or scoring functions making
      the QM information available for automatic molecular recognition in virtual high
      throughput screening.

PMID- 22865256
TI  - Analysis of the projected utility of dabigatran, rivaroxaban, and apixaban and
      their future impact on existing Hematology and Cardiology Anticoagulation Clinics
      at The Johns Hopkins Hospital.
AB  - The purpose of this study is to determine the percentage of patients in the Johns
      Hopkins Anticoagulation Clinics that are potential candidates for the new oral
      anticoagulants, dabigatran, rivaroxaban, and apixaban. A retrospective chart
      review was conducted of patients managed in the Johns Hopkins Cardiology and
      Hematology Anticoagulation Clinics between November 1, 2009 and October 31, 2010.
      Data elements collected include demographics, primary indication for
      anticoagulation, renal function, hepatic function, and concomitant medications.
      These factors were considered against product labeling guidelines and
      inclusion/exclusion criteria from clinical studies to derive candidacy status for
      each oral anticoagulant for each patient. Patients who met at least one caution
      or contraindication criteria were deemed "non-candidates"; potential dosage
      reductions of the new oral anticoagulants were not considered. Four hundred
      ninety-one patients participated in the study. Among participants, 63% would be
      dabigatran candidates, 62% rivaroxaban candidates, and 70% would be candidates
      for apixaban. Dabigatran use would be cautioned against in 34%, rivaroxaban in 18
      %, and apixaban in 30%. Four percent had contraindications to dabigatran, whereas
      21% had contraindications to rivaroxaban. More than 60% of patients in the Johns
      Hopkins Anticoagulation Clinics appear to be potential candidates for each of the
      new oral anticoagulants, assuming they are eventually approved for the same
      indications as warfarin. Many patients fell into the "cautioned" category, which
      demonstrates the complexity associated with selecting candidates for these new
      agents.

PMID- 22865258
TI  - CD44 isoforms in human retinal and choroidal endothelial cells.

PMID- 22865260
TI  - Morning glory disc anomaly with contractile movements.

PMID- 22865259
TI  - Physiological evidence for impairment in autosomal dominant optic atrophy at the
      pre-ganglion level.
AB  - BACKGROUND: Functional studies in patients with autosomal dominant optic atrophy
      (ADOA) are usually confined to analysis of physiological and clinical impact at
      the ganglion cell (GG) and post GC levels. Here we aimed to investigate the
      impact of the disease at a pre-GC level and its correlation with GC/post-GC
      related measures. METHODS: Visual function was assessed in a population of 22
      subjects (44 eyes) from 13 families with ADOA submitted to OPA1 mutation
      analysis. Quantitative psychophysical methods were used to assess konio and
      parvocellular chromatic pathways (Cambridge Colour Test) and distinct achromatic
      spatial frequency channels (Metropsis Contrast Sensitivity Test). Preganglionic
      and GC measures were assessed with the Multifocal Electroretinogram (mfERG) and
      Pattern Electroretinogram (PERG) respectively. Global Pattern and Multifocal VEP
      (visual evoked potentials) were used to assess retinocortical processing, in
      order to characterize impaired processing at the post GC level. Perimetric
      sensitivity, retinal and ganglion cell nerve fibre layer (RNFL) thickness
      measurements were also obtained. RESULTS: Chromatic thresholds were significantly
      increased for protan, deutan and tritan axes (p < < 0.001 for all comparisons)
      and achromatic contrast sensitivity (CS) was reduced for all studied six spatial
      frequency channels (p < < 0.001). We observed significant decreases in
      peripapillary (p <= 0.0008), macular (ring2: p = 0.02; ring 3: p < 0.0001) RNFL,
      as well as in overall retinal thickness (p < 0.0001 in all regions, except the
      central one). Interestingly, we found significant decreases in pre-ganglionic
      multifocal ERG response amplitudes (P1-wave: p <= 0.005) that were correlated
      with retinal thickness (ring 2: r = 0.512; p = 0.026/ring 3: r = 0.583; p =
      0.011) and visual acuity (r = 0.458; p = 0.03, central ring 1). Reductions in GC
      and optic nerve responses amplitude (PERG: p < 0.0001, P50 and N95 components;
      Pattern VEP: p < 0.0001, P100) were accompanied by abnormalities of the MfVEP,
      primarily in central locations (ring 1: p = 0.0007; ring 2: p = 0.012).
      CONCLUSIONS: In the ADOA model of ganglion cell damage, parvo-, konio- and
      magnocellular pathways are concomitantly affected. Structural changes and
      physiological impairment also occurs at a preganglionic level, suggesting a
      retrograde damage mechanism with a significant clinical impact on visual
      function, as shown by correlation analysis. Cortical impairment is only
      moderately explained by the retinal phenotype, suggesting additional damage
      mechanisms at the cortical level.

PMID- 22865261
TI  - Recombinant tissue plasminogen activator, vitrectomy, and gas for recent
      submacular hemorrhage displacement due to retinal macroaneurysm.
AB  - BACKGROUND: The visual prognosis of submacular hemorrhages caused by a retinal
      arterial macroaneurysm (RAM) is poor if left untreated. The use of recombinant
      tissue plasminogen activator (rtPA) has frequently been reported to displace
      submacular hemorrhages from the foveal area in patients with age-related macular
      degeneration. This study aims to investigate the results of displacement of
      recent-onset submacular hemorrhages due to RAM. METHODS: Institutional
      retrospective interventional case series of 12 patients with macular hemorrhage
      due to RAM, who underwent pars plana vitrectomy (PPV); followed in 11 by
      submacular injection of rtPA and gas tamponade. The main outcome measures were
      displacement of the hemorrhage, complication rate, and visual acuity at 1 month
      after surgery and at the last follow-up visit. RESULTS: One month after surgery,
      the hemorrhage had been successfully displaced in ten out of 11 patients. In
      these ten patients, visual acuity (VA) increased by a mean of 1.2 logMAR at 1
      month after surgery. At the last follow-up visit, the mean increase was 1.5
      logMAR. Complications consisted of a vitreous hemorrhage and hyphema, retinal
      detachment, a new submacular hemorrhage, and vitreous hemorrhage after argon
      laser retinal photocoagulation of the RAM. CONCLUSIONS: PPV with submacular rtPA
      and gas injection may successfully displace a recently developed submacular
      hemorrhage in patients with RAM, with a marked improvement in VA that is likely
      to be greater than if left untreated.

PMID- 22865262
TI  - Immunosuppression for interstitial lung disease in systemic sclerosis - novel
      insights and opportunities for translational research.

PMID- 22865264
TI  - Flaws in the peer-reviewing process : a critical look at a recent paper studying
      the role of CCN3 in renal cell carcinoma.
AB  - A critical look at a recently published manuscript reporting the role of CCN3 in
      the regulation of clear cell renal cell carcinoma (RCC) biology raises several
      scientific concerns, and reveals flaws in the reviewing process which appear to
      have resulted in the dissemination of conclusions that are not supported by
      proper experimental procedures. In the example presented here, the observed
      biological effects are attributed to a high molecular weight "CCN3" protein which
      is detected by a single commercial antibody that was not shown in the
      experimental conditions used by the authors to be a valid reagent capable of
      stringently detecting the "canonical" CCN3 protein. Experiments establishing that
      inhibiting the production of high molecular weight "CCN3" protein would reverse
      these biological effects were not performed. The case discussed here clearly
      demonstrates that unreliable data can go through peer reviewing and be published.
      As the data can end up being cited and used as a potential reference by new
      investigators in the field, we believe that such data can throw roadblocks across
      the scientific path of inquiry and mislead investigations. We therefore raise
      awareness for the need of a more stringent peer reviewing process in which
      assurance can be had that the strength and precision of the data have been
      thoroughly checked by experts in the CCN field, and previous work properly
      referenced.

PMID- 22865263
TI  - A common response to common danger? Comparison of animal and plant signaling
      pathways involved in cadmium sensing.
AB  - Exposure to cadmium results in disturbances in cell homeostasis in all living
      organisms. The first response to stress factors, including cadmium, is activation
      of signal transduction pathways that mobilize cell defense mechanisms. The aim of
      this review is a comparison between the signaling network triggered by Cd in
      plants and animals. Despite differences in the structure and physiology of plant
      and animal cells, their cadmium signal transduction pathways share many common
      elements. These elements include signaling molecules such as ROS, Ca(2+) and NO,
      the involvement of phospholipase C, mitogen-activated protein kinase cascades,
      and activation of transcription factors. Undoubtedly, both animals and plants
      also possess specific signaling pathways. In case of animals, Wnt/beta-catenin,
      sonic hedgehog and oestorgen signaling are engaged in the transduction of cadmium
      signal. Plant specific signal transduction pathways include signaling mediated by
      plant hormones. The role of ethylene and jasmonic, salicylic and abscisic acid in
      plant response to cadmium is also discussed.

PMID- 22865265
TI  - Deletion of Cx43 from osteocytes results in defective bone material properties
      but does not decrease extrinsic strength in cortical bone.
AB  - Deletion of connexin (Cx) 43 from osteoblasts and osteocytes (OCN-Cre;Cx43(fl/-)
      mice) or from osteocytes only (DMP1-8kb-Cre;Cx43(fl/fl) mice) results in
      increased cortical, but not cancellous, osteocyte apoptosis and widening of the
      femoral midshaft without changes in cortical thickness. Despite the consequent
      larger moment of inertia, stiffness and ultimate load, measures of mechanical
      strength assessed by three-point bending, are not higher in either model of Cx43
      deficiency due to reduced Young's modulus, a measure of the stiffness of the
      material per unit of area. In OCN-Cre;Cx43(fl/-) mice, this was accompanied by a
      reduced ratio of nonreducible/reducible collagen cross-links as assessed by
      Fourier transformed infrared imaging (FTIRI) in the femoral diaphysis. On the
      other hand, DMP1-8kb-Cre;Cx43(fl/fl) mice did not show a significant reduction in
      collagen maturation in the same skeletal site, but a small decrease in
      mineralization was detected by FTIRI. Remarkably, both osteoblastic and
      osteocytic cells lacking Cx43 expressed lower mRNA levels of lysyl oxidase, a
      crucial enzyme involved in collagen maturation. These findings suggest that Cx43
      expression in osteoblasts is involved in maintaining the quality of the bone
      matrix in cortical bone through the maturation of collagen cross-links.
      Osteocytic Cx43 expression is important also to maintain the stiffness of the
      bone material, where Cx43 deficiency results in local reduction in
      mineralization, possibly due to osteocyte apoptosis.

PMID- 22865266
TI  - Sipuleucel-T immune parameters correlate with survival: an analysis of the
      randomized phase 3 clinical trials in men with castration-resistant prostate
      cancer.
AB  - PURPOSE: Sipuleucel-T, the first FDA-approved autologous cellular immunotherapy
      for treatment of advanced prostate cancer, is manufactured by activating
      peripheral blood mononuclear cells, including antigen presenting cells (APCs),
      with a fusion protein containing prostatic acid phosphatase. Analysis of data
      from three phase 3 trials was performed to immunologically characterize this
      therapy during the course of the three doses, and to relate the immunological
      responses to overall survival (OS). METHODS: Sipuleucel-T product characteristics
      [APC numbers, APC activation (CD54 upregulation), and total nucleated cell (TNC)
      numbers] were assessed in three randomized, controlled phase 3 studies (N = 737).
      Antigen-specific cellular and humoral responses were assessed in a subset of
      subjects. The relationships between these parameters and OS were assessed.
      RESULTS: APC activation occurred in the first dose preparation [6.2-fold, (4.65,
      7.70); median (25th, 75th percentile)] and increased in the second [10.6-fold
      (7.83, 13.65)] and third [10.5-fold (7.89, 13.65)] dose preparations. Cytokines
      and chemokines associated with activated APCs were produced during the
      manufacture of each dose; T-cell activation-associated cytokines were detected in
      the second and third dose preparations. Antigen-specific T cells were detectable
      after administration of the first sipuleucel-T dose. Cumulative APC activation,
      APC number, and TNC number correlated with OS (P < 0.05). Antigen-specific immune
      responses were observed in 78.8 % of monitored subjects and their presence
      correlated with OS (P = 0.003). CONCLUSION: Sipuleucel-T broadly engages the
      immune system by activating APCs ex vivo and inducing long-lived immune responses
      in vivo. These data indicate antigen-specific immune activation as a mechanism by
      which sipuleucel-T prolongs OS.

PMID- 22865267
TI  - Memory T cells are uniquely resistant to melanoma-induced suppression.
AB  - We have previously observed that in vivo exposure to growing melanoma tumors
      fundamentally alters activated T cell homeostasis by suppressing the ability of
      naive T cells to undergo antigen-driven proliferative expansion. We hypothesized
      that exposure of T cells in later stages of differentiation to melanoma would
      have similar suppressive consequences. C57BL/6 mice were inoculated with media or
      syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic
      choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells
      were quantified using flow cytometry 18 days after tumor inoculation. Inoculation
      with melanoma on post-infection day 8 potentiated the contraction of previously
      activated T cells. This enhanced contraction was associated with increased
      apoptotic susceptibility among T cells from tumor-bearing mice. In contrast,
      inoculation with melanoma on post-infection day 60 did not affect the ability of
      previously established memory T cells to maintain themselves in stable numbers.
      In addition, the ability of previously established memory T cells to respond to
      LCMV challenge was unaffected by melanoma. Following adoptive transfer into
      melanoma-bearing mice, tumor-specific memory T cells were significantly more
      effective at controlling melanoma growth than equivalent numbers of tumor
      specific effector T cells. These observations suggest that memory T cells are
      uniquely resistant to suppressive influences exerted by melanoma on activated T
      cell homeostasis; these findings may have implications for T cell-based cancer
      immunotherapy.

PMID- 22865268
TI  - Increased prevalence of tumor-infiltrating regulatory T cells is closely related
      to their lower sensitivity to H2O2-induced apoptosis in gastric and esophageal
      cancer.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Although an increase in regulatory T cells
      (Tregs) is observed in tumor microenvironments, the underlying mechanism is not
      fully clarified. Since it was suggested that Tregs showed a lower sensitivity
      toward oxidative stress in comparison with conventional T cells, in the present
      study, we investigated the H(2)O(2) production and apoptosis of Tregs in gastric
      and esophageal cancer tissues, employing flow cytometric analysis using fresh
      samples (n = 93) and immunohistochemical analysis (n = 203). RESULTS: The
      increased tumor-infiltrating Tregs coexisted with elevated H(2)O(2) production
      according to disease progression. The grade of apoptosis in Tregs was less
      pronounced than that in conventional T cells, and there was a positive
      correlation between H(2)O(2) production and the grade of apoptosis in
      conventional T cells, while there was no correlation between H(2)O(2) production
      and the grade of apoptosis in Tregs. Moreover, Tregs were less sensitive to
      H(2)O(2)-induced apoptosis compared with conventional T cells in vitro.
      CONCLUSIONS: We have demonstrated that the increased prevalence of tumor
      infiltrating Tregs closely related to their lower sensitivity to H(2)O(2)-induced
      apoptosis.

PMID- 22865269
TI  - Helical CT-enteroclysis in the detection of small-bowel tumours: a meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis to determine sensitivity and specificity
      estimates of helical CT-enteroclysis in the detection of small-bowel tumours.
      METHODS: A search for relevant articles published from January 1992 to November
      2010 was performed. Study design, patient characteristics and 2 * 2 contingency
      tables were recorded for eligible studies. Heterogeneity was assessed with the I
      (2) statistic. A bivariate generalised linear random-effects model was used to
      summarise sensitivity and specificity estimates for small-bowel tumour detection
      on a per-patient basis. Sensitivity and specificity estimates were compared in
      different subgroups. RESULTS: Twelve studies (696 patients) were eligible. The
      mean small-bowel tumour prevalence was 22.6 % (range 7.7-45.8 %). Inter-study
      heterogeneity was substantial for sensitivity (I (2) = 66.9 %; 95 % CI 28.7-88.5
      %) and low for specificity (I (2) = 10.6 %; 95 % CI 0.0-55.0 %). On a per-patient
      basis, pooled sensitivity was 92.8 % (95 % CI 71.3-98.5 %) and pooled specificity
      99.2 % (95 % CI 94.2-99.9 %) for the diagnosis of small-bowel tumour. Subgroup
      analysis revealed that small-bowel preparation, more than one imaging pass and
      large volumes (>=2 L) of enteral contrast agent did not improve tumour detection.
      CONCLUSION: Our meta-analysis confirms that helical CT-enteroclysis has high
      degrees of sensitivity and specificity for small-bowel tumour detection. However,
      our findings reinforce the need for more standardised individual studies.

PMID- 22865270
TI  - Diffusion-weighted MR imaging including bi-exponential fitting for the detection
      of recurrent or residual tumour after (chemo)radiotherapy for laryngeal and
      hypopharyngeal cancers.
AB  - OBJECTIVES: To assess whether diffusion-weighted magnetic resonance imaging (DW
      MRI) including bi-exponential fitting helps to detect residual/recurrent tumours
      after (chemo)radiotherapy of laryngeal and hypopharyngeal carcinoma. METHODS:
      Forty-six patients with newly-developed/worsening symptoms after
      (chemo)radiotherapy for laryngeal/hypopharyngeal cancers were prospectively
      imaged using conventional MRI and axial DW-MRI. Qualitative (visual assessment)
      and quantitative analysis (mono-exponentially: total apparent diffusion
      coefficient [ADC(T)], and bi-exponentially: perfusion fraction [F(P)] and true
      diffusion coefficient [ADC(D)]) were performed. Diffusion parameters of tumour
      versus post-therapeutic changes were compared, with final diagnosis based on
      histopathology and follow-up. Mann-Whitney U test was used for statistical
      analysis. RESULTS: Qualitative DW-MRI combined with morphological images allowed
      the detection of tumour with a sensitivity of 94% and specificity 100%. ADC(T)
      and ADC(D) values were lower in tumour with values 120 +/- 49 * 10(-5) mm(2)/s
      and 113 +/- 50 * 10(-5) mm(2)/s, respectively, compared with post-therapeutic
      changes with values 182 +/- 41 * 10(-5) mm(2)/s (P < 0.0002) and 160 +/- 47 * 10(
      5) mm(2)/s (P < 0.003), respectively. F(P) values were significantly lower in
      tumours than in non-tumours (13 +/- 9% versus 31 +/- 16%, P < 0.0002), with F(P)
      being the best quantitative parameter for differentiation between post
      therapeutic changes and recurrence. CONCLUSIONS: DW-MRI in combination with
      conventional MRI substantially improves detection and exclusion of tumour in
      patients with laryngeal and hypopharyngeal cancers after treatment with
      (chemo)radiotherapy on both qualitative and quantitative analysis, with F(P)
      being the best quantitative parameter in this context.

PMID- 22865271
TI  - Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR
      Contrast Medium Safety Committee guidelines.
AB  - PURPOSE: To update the guidelines of the Contrast Media Safety Committee (CMSC)
      of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic
      fibrosis and gadolinium-based contrast media. AREAS COVERED: Topics reviewed
      include the history, clinical features and prevalence of nephrogenic systemic
      fibrosis and the current understanding of its pathophysiology. The risk factors
      for NSF are discussed and prophylactic measures are recommended. The stability of
      the different gadolinium-based contrast media and the potential long-term effects
      of gadolinium in the body have also been reviewed.

PMID- 22865272
TI  - SLAP tears: diagnosis using 3-T shoulder MR arthrography with the 3D isotropic
      turbo spin-echo space sequence versus conventional 2D sequences.
AB  - OBJECTIVES: The aim of this study was to determine the accuracy and reliability
      of shoulder magnetic resonance (MR) arthrography with three-dimensional (3D)
      isotropic intermediate-weighted turbo spin-echo (TSE) sampling perfection with
      application-optimised contrasts using different flip angle evolution (SPACE) in
      the diagnosis of superior labrum anterior-to-posterior (SLAP) lesions compared
      with two-dimensional (2D) TSE at 3.0 T. METHODS: MR arthrograms, including 2D TSE
      and 3D TSE-SPACE, in 87 patients who underwent arthroscopy were retrospectively
      analysed by two reviewers for the presence and type of SLAP lesions. Sensitivity
      and specificity were compared using McNemar's test, and inter-observer agreement
      was calculated using Cohen's kappa. Receiver operating characteristic (ROC) curve
      analyses were performed. RESULTS: The mean sensitivity, specificity and accuracy
      were 90%, 85% and 86% for 2D TSE, and 81%, 86% and 85% for 3D TSE-SPACE
      respectively, with no statistically significant differences. Inter-observer
      agreements were substantial in 2D TSE (kappa = 0.76) and 3D TSE-SPACE (kappa =
      0.68). The areas under the ROC curves were 0.92 for 2D TSE and 0.90 for 3D TSE
      SPACE, which were not significantly different. CONCLUSIONS: MR arthrography with
      3D TSE-SPACE showed comparable accuracy and substantial inter-observer agreement
      for the diagnosis of SLAP lesions.

PMID- 22865273
TI  - Occurrence of coring after needle insertion through a rubber stopper: study with
      prednisolone acetate.
AB  - OBJECTIVES: To evaluate the occurrence of coring after needle insertion through
      the rubber stopper of prednisolone acetate vials. METHODS: Two-hundred vials of
      prednisolone acetate were randomly distributed to two radiologists. Prednisolone
      acetate was drawn up through the rubber bung of the vials with an 18-gauge
      cutting bevelled needle and aspirated with a 5-ml syringe. The presence of coring
      was noted visually. We systematically put each core in a syringe refilled with 3
      ml prednisolone acetate, and injected the medication through a 20-gauge spine
      needle. Computed tomography was performed to measure the size of each coring.
      RESULTS: Coring occurred in 21 out of 200 samples (10.5 %), and was visually
      detected in the syringe filled up with prednisolone in 11 of the 21 cases. Ten
      more occult cores were detected only after the syringes and needles were taken
      apart and rinsed. The core size ranged from 0.6 to 1.1 mm, and 1 of the 21 (4.7
      %) cores was ejected through the 20-gauge needle. CONCLUSION: Coring can occur
      after the insertion of a needle through the rubber stopper of a vial of
      prednisolone acetate, and the resultant core can then be aspirated into the
      syringe.

PMID- 22865274
TI  - Intelligent image retrieval based on radiology reports.
AB  - OBJECTIVES: To create an advanced image retrieval and data-mining system based on
      in-house radiology reports. METHODS: Radiology reports are semantically analysed
      using natural language processing (NLP) techniques and stored in a state-of-the
      art search engine. Images referenced by sequence and image number in the reports
      are retrieved from the picture archiving and communication system (PACS) and
      stored for later viewing. A web-based front end is used as an interface to query
      for images and show the results with the retrieved images and report text. Using
      a comprehensive radiological lexicon for the underlying terminology, the search
      algorithm also finds results for synonyms, abbreviations and related topics.
      RESULTS: The test set was 108 manually annotated reports analysed by different
      system configurations. Best results were achieved using full syntactic and
      semantic analysis with a precision of 0.929 and recall of 0.952. Operating
      successfully since October 2010, 258,824 reports have been indexed and a total of
      405,146 preview images are stored in the database. CONCLUSIONS: Data-mining and
      NLP techniques provide quick access to a vast repository of images and radiology
      reports with both high precision and recall values. Consequently, the system has
      become a valuable tool in daily clinical routine, education and research. KEY
      POINTS: Radiology reports can now be analysed using sophisticated natural
      language-processing techniques. Semantic text analysis is backed by terminology
      of a radiological lexicon. The search engine includes results for synonyms,
      abbreviations and compositions. Key images are automatically extracted from
      radiology reports and fetched from PACS. Such systems help to find diagnoses,
      improve report quality and save time.

PMID- 22865275
TI  - Predictive value of T2-weighted imaging and contrast-enhanced MR imaging in
      assessing myometrial invasion in endometrial cancer: a pooled analysis of
      prospective studies.
AB  - BACKGROUND: To obtain diagnostic performance values of T2-weighted imaging (T2WI)
      and contrast-enhanced magnetic resonance imaging (CE-MRI) in the prediction of
      myometrial invasion in patients with endometrial cancer. METHODS: Databases
      including MEDLINE and EMBASE were searched for relevant original articles
      published from January 1995 to March 2012. Pooled estimation data were obtained
      by statistical analysis. RESULTS: Eleven articles (548 patients) were included.
      For assessing any myometrial involvement, the pooled sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) for CE-MRI
      were 0.81 (95% CI, 0.72, 0.88), 0.72 (95% CI, 0.64, 0.79), 0.65 (95% CI, 0.56,
      0.73) and 0.85 (95% CI, 0.78, 0.91); for T2WI, they were 0.87 (95% CI, 0.78,
      0.94), 0.58 (95% CI, 0.47, 0.69), 0.64 (95% CI, 0.54, 0.73), 0.84 (95% CI, 0.73,
      0.92) respectively. The pooled specificity of CE-MRI (0.72) was significantly
      higher than T2WI (0.58) (P < 0.05). For assessing deep myometrial involvement,
      there was no statistically significant difference between CE-MRI and T2WI, (P >
      0.05). CONCLUSIONS: CE-MRI has a good diagnostic performance in the prediction of
      any myometrial invasion and is superior to T2WI. But its PPV is somewhat
      suboptimal. For assessing deep myometrial involvement, its NPV appears relative
      high and negative findings strongly suggest an absence of deep myometrial
      involvement, which can guide therapeutic decision-making.

PMID- 22865276
TI  - Two- versus three-dimensional dual gradient-echo MRI of the liver: a technical
      comparison.
AB  - OBJECTIVE: To compare 2D spoiled dual gradient-echo (SPGR-DE) and 3D SPGR-DE with
      fat and water separation for the assessment of focal and diffuse fatty
      infiltration of the liver. METHODS: A total of 227 consecutive patients (141 men;
      56 +/- 14 years) underwent clinically indicated liver MRI at 1.5 T including
      multiple-breath-hold 2D SPGR-DE and single-breath-hold 3D SPGR-DE with automatic
      reconstruction of fat-only images. Two readers assessed the image quality and
      number of fat-containing liver lesions on 2D and 3D in- and opposed-phase (IP/OP)
      images. Liver fat content (LFC) was quantified in 138 patients without chronic
      liver disease from 2D, 3D IP/OP, and 3D fat-only images. RESULTS: Mean durations
      of 3D and 2D SPGR-DE acquisitions were 23.7 +/- 2.9 and 97.2 +/- 9.1 s
      respectively. The quality of all 2D and 3D images was rated diagnostically. Three
      dimensional SPGR-DE revealed significantly more breathing artefacts resulting in
      lower image quality (P < 0.001); 2D and 3D IP/OP showed a similar detection rate
      of fat-containing lesions (P = 0.334) and similar LFC estimations (mean: +0.4 %;
      P = 0.048). LFC estimations based on 3D fat-only images showed significantly
      higher values (mean: 2.7 % + 3.5 %) than those from 2D and 3D IP/OP images (P <
      0.001). CONCLUSION: Three dimensional SPGR-DE performs as well as 2D SPGR-DE for
      the assessment of focal and diffuse fatty infiltration of liver parenchyma. The
      3D SPGR-DE sequence used was quicker but more susceptible to breathing artefacts.
      Significantly higher LFC values are derived from 3D fat-only images than from 2D
      or 3D IP/OP images.

PMID- 22865279
TI  - Absence of Galectin-1 accelerates CD8+ T cell-mediated graft rejection.
AB  - Galectin-1 (Gal-1) is a member of a family of endogenous beta-galactose-binding
      proteins with a role in preventing autoimmune diseases and chronic inflammation.
      In this study, the involvement of Gal-1 in graft rejection was investigated by
      using Gal-1-deficient mice (Gal-1-/-). We demonstrate that in the absence of Gal
      1, skin grafts are rejected earlier compared with those of WT mice, and that this
      is due to the role played by CD8+ T cells in graft rejection. The difference in
      graft survival observed between Gal-1-/- and WT mice was explained by both an
      increase in the percentage of antigen-specific CD8+ T cells and by preferential
      secretion of IFN-gamma and IL-17 by CD8+ T cells in Gal-1-/- mice compared with
      WT mice. This study suggests that endogenous expression of Gal-1 contributes to
      graft survival. The results obtained from the use of mice deficient in Gal-1 also
      confirm a key role for CD8+ T cells in graft rejection.

PMID- 22865280
TI  - Successful management of intractable chylothorax in Gorham-Stout disease by awake
      thoracoscopic surgery.
AB  - Gorham-Stout is an extremely rare disease, which is characterized by
      proliferation of vascular and lymphatic bone structures. A 15-year-old male
      patient was the diagnosis of Gorham-Stout disease of the cervical spine with
      chylothorax. Awake thoracoscopic ablation was performed using bronchoscopic tools
      and awake thoracoscopic debridement of the thoracoscopic cavities and chemical
      pleurodesis with OK-432 were repeated. The amount of drained liquid was
      controlled. There was no recurrence of pleural effusion.

PMID- 22865281
TI  - Left lower apical segmentectomy after video-assisted left upper lobectomy for
      relapse in lung cancer: benefit to avoid completion pneumonectomy.
AB  - Segmental resection is a useful procedure to preserve respiratory function. We
      report a case of lower apical segmentectomy for relapse after initial video
      assisted left upper lobectomy to avoid completion pneumonectomy. After 4 years of
      follow-up, the patient is doing well with no evidence of disease.

PMID- 22865282
TI  - A functional screening identifies five microRNAs controlling glypican-3: role of
      miR-1271 down-regulation in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the major primary liver cancer. Glypican-3
      (GPC3), one of the most abnormally expressed genes in HCC, participates in liver
      carcinogenesis. Based on data showing that GPC3 expression is
      posttranscriptionally altered in HCC cells compared to primary hepatocytes, we
      investigated the implication of microRNAs (miRNAs) in GPC3 overexpression and
      HCC. To identify GPC3-regulating miRNAs, we developed a dual-fluorescence FunREG
      (functional, integrated, and quantitative method to measure posttranscriptional
      regulations) system that allowed us to screen a library of 876 individual miRNAs.
      Expression of candidate miRNAs and that of GPC3 messenger RNA (mRNA) was measured
      in 21 nontumoral liver and 112 HCC samples. We then characterized the phenotypic
      consequences of modulating expression of one candidate miRNA in HuH7 cells and
      deciphered the molecular mechanism by which this miRNA controls the
      posttranscriptional regulation of GPC3. We identified five miRNAs targeting GPC3
      3'-untranslated region (UTR) and regulating its expression about the 876 tested.
      Whereas miR-96 and its paralog miR-1271 repressed GPC3 expression, miR-129-1-3p,
      miR-1291, and miR-1303 had an inducible effect. We report that miR-1271
      expression is down-regulated in HCC tumor samples and inversely correlates with
      GPC3 mRNA expression in a particular subgroup of HCC. We also report that miR
      1271 inhibits the growth of HCC cells in a GPC3-dependent manner and induces cell
      death. CONCLUSION: Using a functional screen, we found that miR-96, miR-129-1-3p,
      miR-1271, miR-1291, and miR-1303 differentially control GPC3 expression in HCC
      cells. In a subgroup of HCC, the up-regulation of GPC3 was associated with a
      concomitant down-regulation of its repressor miR-1271. Therefore, we propose that
      GPC3 overexpression and its associated oncogenic effects are linked to the down
      regulation of miR-1271 in HCC.

PMID- 22865283
TI  - Impact of probiotic-supplemented diet on the expression level of lactate
      dehydrogenase in the leukocytes of rabbits.
AB  - Probiotics are known as living, nonpathogenic microorganisms that colonize the
      intestine and provide benefit to the host. The present study aims to measure one
      important energy metabolism-related enzyme activity in blood of rabbits fed on
      probiotics of recommended concentration. In addition, it also aims for the
      evaluation of the expression level of lactate dehydrogenase (LDH) enzyme using
      reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Two groups of
      rabbits are used: control group receiving normal standardized diet and the other
      probiotic-supplemented group receiving the same diet containing probiotic,
      namely, Mega acidophilus (200 million cfu/kg body weight/day) for 4 weeks. The
      obtained results revealed that the rabbits supplemented with probiotics showed a
      significant decrease in the levels of serum total cholesterol (TC),
      triacylglycerol, high-density lipoprotein cholesterol (HDL-c) and low-density
      lipoprotein cholesterol (LDL-c) when compared with control group. Risk factors
      detected by measuring TC/HDL-c and LDL-c/HDL-c ratios showed statistically
      significant decrease in probiotic-supplemented rabbits when compared with control
      group. In addition, blood glucose and total LDH activity were elevated in
      probiotic-supplemented rabbits when compared with control group. RT-PCR products
      of LDH-M gene produced two specific amplicons. One amplicon has the expected size
      of 243 bp from all samples of rabbits as revealed by GelPro software. The level
      of LDH-M expression was found to be increased in the probiotic-supplemented
      group. However, unexpected amplicons are produced at 586 bp in all the samples,
      which may be a dimeric form of the amplified region. It was concluded that this
      probiotic blend is beneficiary for the metabolic reactions of lipids in the body.
      Moreover, LDH expression level can be considered as a biomarker for the effect of
      probiotic and hence monitoring the metabolic changes as reflected from its
      administration. 

PMID- 22865284
TI  - Protective effect of lycopene on deltamethrin-induced histological and
      ultrastructural changes in kidney tissue of rats.
AB  - Deltamethrin is globally used in crop protection and control of malaria and other
      vector-borne diseases. It has a potent insecticidal activity with an appreciable
      safety margin. However, a number of studies have demonstrated nephrotoxicity of
      deltamethrin in mammalian and nonmammalian species. Lycopene, a carotenoid
      occurring naturally in tomatoes, has attracted considerable attention as an
      antioxidant. This study was focused on investigating the possible protective
      effect of coadministration of lycopene on deltamethrin toxicity. In this study,
      male albino rats were divided into four groups of 10 animals each: group I served
      as control, which received standard diet; group II received oral administration
      of deltamethrin (1.28 mg/kg per day) for 30 days; group III received both
      deltamethrin and lycopene (1 mg/kg per day); group IV received lycopene (1 mg/kg
      per day). After the experiment, the animals were anesthetized and the cytokine,
      tumor necrosis factor-alpha (TNF-alpha), in the serum was measured; the kidney
      was taken for histological and ultrastructural studies. Deltamethrin
      significantly increased the TNF-alpha. The histopathological examination of
      kidney showed mild necrotic changes. Ultrastructural changes in renal proximal
      tubules of deltamethrin-treated group included an increased number and irregular
      shape of mitochondria with sparse fragmented cristae, serious ultrastructural
      lesions in renal proximal tubular lining cells, vacuolar degeneration in the
      epithelial cells, increased number of lysosomes and loss of apical microvilli. In
      addition, focal segmental thickening and the duplication of glomerular basement
      membrane and podocyte changes were observed. Histopathological and
      ultrastructural study showed some protective effect of lycopene on kidney
      tissues. 

PMID- 22865285
TI  - The breeding systems of diploid and neoautotetraploid clones of Acacia mangium
      Willd. in a synthetic sympatric population in Vietnam.
AB  - Colchicine-induced neoautotetraploid genotypes of Acacia mangium were cloned and
      planted in mixture with a set of diploid clones in an orchard in southern
      Vietnam. Following good general flowering, open-pollinated seed was collected
      from trees of both cytotypes and microsatellite markers were used to determine
      the breeding system as characterised by the proportion of outcrosses in young
      seedling progeny. As predicted from the literature, the progeny of diploid clones
      were predominantly outcrossed (t(m) = 0.97). In contrast, the progeny of the
      tetraploid clones were almost entirely selfs (t(m) = 0.02; 3 of 161 seedlings
      assayed were tetraploid outcrosses and there were no triploids). Segregation at
      loci heterozygous in the tetraploid mothers followed expected ratios, indicating
      sexual reproduction rather than apomixis. Post-zygotic factors are primarily
      responsible for divergence of the breeding systems. Commonly, less than 1 % of
      Acacia flowers mature as a pod, and after mixed pollination, diploid outcrossed
      seed normally develops at the expense of selfs. Selfs of the tetraploid trees
      appear to express less genetic load and have a higher probability of maturing.
      However, this does not fully explain the observed deficiency of outcross
      tetraploid progeny. Presumably, there are cytogenetic reasons which remain to be
      investigated. In nature, selfing would increase the probability of establishment
      of neotetraploids irrespective of cytotype frequency in the population. Breeders
      need to review their open-pollinated breeding and seed production strategies. It
      remains to be seen whether this is an ephemeral problem, with strong fertility
      selection restoring potential for outcrossing over generations.

PMID- 22865286
TI  - Endoscopic evaluation of primary tumor response in patients with metastatic
      colorectal cancer treated by systemic chemotherapy.
AB  - BACKGROUND: The number of cases of metastatic colorectal cancer treated by
      chemotherapy without primary tumor resection has recently increased. However,
      evaluation of primary tumor response by computed tomography is difficult in such
      cases. In this study, the usefulness of evaluation of primary tumor response to
      chemotherapy by endoscopy was investigated. METHODS: This retrospective analysis
      was performed at the Shizuoka Cancer Center and included 31 patients (88
      evaluations) with metastatic colorectal cancer. Computed tomography and endoscopy
      were performed concomitantly between September 2002 and June 2006. Patients were
      treated by systemic chemotherapy without prophylactic primary tumor resection.
      Definitions of primary tumor response were as follows: (1) complete response,
      confirmed by colorectal biopsy; (2) progressive disease, enlargement of at least
      one of five tumor parameters; and (3) neither (1) nor (2). Computed tomography
      was performed to evaluate primary tumor response according to the Response
      Evaluation Criteria in Solid Tumors and to identify colorectal stenosis secondary
      to primary tumors. RESULTS: The rate of concordance between endoscopy and
      computed tomography for evaluation of primary tumor response was 75%. Colorectal
      stenosis was detected 14 times by endoscopy (9 cases) and 3 times by computed
      tomography (3 cases). Of the 7 patients in whom surgery was required, 6 exhibited
      stenotic symptoms before endoscopic detection. CONCLUSIONS: With regard to
      primary tumor response evaluation, a high concordance rate was observed between
      endoscopy and computed tomography, although endoscopic evaluation appeared more
      sensitive in detecting colorectal stenosis requiring surgical treatment.

PMID- 22865287
TI  - Long-term effects of injection laryngoplasty with a temporary agent on voice
      quality and vocal fold position.
AB  - OBJECTIVES/HYPOTHESIS: Patients with unilateral vocal fold paralysis (UVFP)
      treated with temporary injection laryngoplasty (IL) have a decreased rate of
      permanent medialization laryngoplasty (ML) compared to UVFP patients initially
      treated by observation. The aim of this study was to determine whether the lower
      rate of ML corresponded with improved quantifiable measures. STUDY DESIGN:
      Retrospective review. METHODS: Examinations at presentation and follow-up of 14
      IL patients and 24 observation patients were analyzed for laryngoscopic features
      and Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scores. RESULTS:
      The groups were similar at presentation. At follow-up, the IL group showed
      significant improvement in 11/18 laryngoscopic criteria and 7/12 CAPE-V
      parameters compared to the observation group (P < .05). The observation group
      underwent ML more frequently than the IL group (75% vs. 29%, P = .008).
      CONCLUSIONS: The lower rate of permanent ML in patients undergoing temporary IL
      corresponds with improvements in CAPE-V scores and laryngoscopic features.
      Improvements persisted beyond the accepted time frame for temporary graft
      resorption.

PMID- 22865288
TI  - A fatal case of thallium toxicity: challenges in management.
AB  - BACKGROUND: Thallium is a highly toxic compound and is occasionally involved in
      intentional overdoses or criminal poisonings. Accidental poisonings also occur,
      but are increasingly rare owing to restricted use and availability of thallium.
      We report a fatal suicidal ingestion of thallium sulfate rodenticide in which
      multi-dose activated charcoal (MDAC) and Prussian Blue (PB) were both used
      without changing the outcome. CASE REPORT: A 36 year old man ingested an unknown
      amount of thallium sulfate grains from an old rodenticide bottle. He presented to
      an emergency department (ED) 45 minutes later with abdominal pain and vomiting.
      On examination he was agitated with a blood pressure of 141/60 mmHg and a heart
      rate of 146 beats per minute (bpm). He received MDAC during his initial ED
      management and was started on PB 18 hours post arrival; he was intubated on the
      following day for airway protection. The patient continued to be tachycardic and
      hypertensive and subsequently developed renal failure. On hospital day three, the
      patient developed hypotension that did not respond to fluids. The patient
      required vasopressors and was transferred to a tertiary care center to undergo
      continuous renal replacement therapy (CRRT). The patient died shortly after his
      transfer. His last blood thallium concentration was 5369 mcg/L, a spot urine
      thallium >2000 mcg/L, and a 24- hour urine thallium was >2000 mcg/L. CONCLUSION:
      Though extremely rare, thallium intoxication can be lethal despite early
      administration of MDAC and use of Prussian blue therapy. Rapid initiation of
      hemodialysis can be considered in cases of severe thallium poisoning, to remove
      additional thallium, to correct acid-base disturbance, or to improve renal
      function.

PMID- 22865289
TI  - Impact of cell wall-degrading enzymes on water-holding capacity and solubility of
      dietary fibre in rye and wheat bran.
AB  - BACKGROUND: Rye and wheat bran were treated with several xylanases and
      endoglucanases, and the effects on physicochemical properties such as solubility,
      viscosity, water-holding capacity and particle size as well as the chemical
      composition of the soluble and insoluble fractions of the bran were studied. A
      large number of enzymes with well-defined activities were used. This enabled a
      comparison between enzymes of different origins and with different activities as
      well as a comparison between the effects of the enzymes on rye and wheat bran.
      RESULTS: The xylanases derived from Bacillus subtilis were the most effective in
      solubilising dietary fibre from wheat and rye bran. There was a tendency for a
      higher degree of degradation of the soluble or solubilised dietary fibre in rye
      bran than in wheat bran when treated with most of the enzymes. CONCLUSION: None
      of the enzymes increased the water-holding capacity of the bran or the viscosity
      of the aqueous phase. The content of insoluble material decreased as the dietary
      fibre was solubilised by the enzymes. The amount of material that may form a
      network to retain water in the system was thereby decreased.

PMID- 22865290
TI  - The effects of cumulative risk and protection on problem behaviors for youth in
      an urban school-based system of care.
AB  - The present study examined the cumulative effects of risk and protective factors
      on internalizing and externalizing problems for a sample of youth who were
      diagnosed with a severe emotional disturbance and enrolled in an urban school
      based system of care. The sample included 139 Latino and African American
      children (ages 5-19; 65 % male) and their families. After controlling for
      demographic variables, the results of hierarchical multiple regression analyses
      revealed that cumulative risk and protection were significantly related to
      internalizing problem behaviors, and cumulative protection was negatively related
      to externalizing problem behaviors. The findings support the importance of
      including or increasing strength building approaches, in addition to risk
      reduction, in order to maximize prevention and intervention efforts for system-of
      care populations.

PMID- 22865291
TI  - Frequency separation by an excitatory-inhibitory network.
AB  - We consider a situation in which individual features of the input are represented
      in the neural system by different frequencies of periodic firings. Thus, if two
      of the features are presented concurrently, the input to the system will consist
      of a superposition of two periodic trains. In this paper we present an algorithm
      that is capable of extracting the individual features from the composite signal
      by separating the signal into periodic spike trains with different frequencies.
      We show that the algorithm can be implemented in a biophysically based excitatory
      inhibitory network model. The frequency separation process works over a range of
      frequencies determined by time constants of the model's intrinsic variables. It
      does not rely on a "resonance" phenomenon and is not tuned to a discrete set of
      frequencies. The frequency separation is still reliable when the timing of
      incoming spikes is noisy.

PMID- 22865292
TI  - The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs
      NFATc1 translocation, and decreases in vitro osteoclastogenesis.
AB  - Vacuolar H(+) -ATPase (V-ATPase), a multisubunit enzyme located at the ruffled
      border and in lysosomes of osteoclasts, is necessary for bone resorption. We
      previously showed that heterozygous mice with an R740S mutation in the a3 subunit
      of V-ATPase (+/R740S) have mild osteopetrosis resulting from an ~90% reduction in
      proton translocation across osteoclast membranes. Here we show that lysosomal pH
      is also higher in +/R740S compared with wild-type (+/+) osteoclasts. Both
      osteoclast number and size were decreased in cultures of +/R740S compared with
      +/+ bone marrow cells, with concomitant decreased expression of key osteoclast
      markers (TRAP, cathepsin K, OSCAR, DC-STAMP, and NFATc1), suggesting that low
      lysosomal pH plays an important role in osteoclastogenesis. To elucidate the
      molecular mechanism of this inhibition, NFATc1 activation was assessed. NFATc1
      nuclear translocation was significantly reduced in +/R740S compared with +/+
      cells; however, this was not because of impaired enzymatic activity of
      calcineurin, the phosphatase responsible for NFATc1 dephosphorylation. Protein
      and RNA expression levels of regulator of calcineurin 1 (RCAN1), an endogenous
      inhibitor of NFATc1 activation and a protein degraded in lysosomes, were not
      significantly different between +/R740S and +/+ osteoclasts, but the RCAN1/NFATc1
      ratio was significantly higher in +/R740S versus +/+ cells. The lysosomal
      inhibitor chloroquine significantly increased RCAN1 accumulation in +/+ cells,
      consistent with the hypothesis that higher lysosomal pH impairs RCAN1
      degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1
      inhibition. Our data indicate that increased lysosomal pH in osteoclasts leads to
      decreased NFATc1 signaling and nuclear translocation, resulting in a cell
      autonomous impairment of osteoclastogenesis in vitro.

PMID- 22865293
TI  - Moyamoya arteriopathy.
AB  - OPINION STATEMENT: The arteriopathy of moyamoya is progressive and results in
      severe disability from cerebral ischemia. Once the diagnosis is confirmed with
      magnetic resonance imaging (MRI) and catheter angiography, initial measures
      should consist of administration of low dose aspirin (usually 81 mg daily,
      barring pre-existing contraindications), maintenance of good hydration and
      avoidance of hyperventilation (to reduce the risk of reflex cerebral
      vasoconstriction). Definitive treatment is predicated on surgical
      revascularization of the affected cerebral hemispheres. Operative treatment
      should be undertaken at a high-volume center with experienced surgeons and
      anesthesia staff. The specific technique employed depends on the individual
      presentation and surgeon preference, although most centers will offer indirect
      approaches such as pial synangiosis to children and young adults, with direct
      bypass often reserved for older patients or those presenting with crescendo
      symptoms. Follow-up is important, with postoperative imaging (either MRI or
      catheter angiogram) and office visits to confirm surgical efficacy and resolution
      of symptoms.

PMID- 22865294
TI  - Strategies to augment recovery after stroke.
AB  - OPINION STATEMENT: The improvement of recovery after stroke remains one of the
      main priorities for patients with stroke. Acute de-occlusion of the artery should
      improve patient outcome and recovery. Recent data and meta-analysis confirmed the
      efficacy of IV thrombolysis when administered to selected patients less than 4.5
      hours after the onset of ischemic stroke even in patients aged > 80 years. IV
      thrombolysis with rTPA is currently the only validated treatment for the acute
      phase of ischemic stroke. This has lead to a major public health effort to create
      stroke treatment units in developed countries. Mechanical thrombectomy is not yet
      validated despite major support from clinicians and the industry overall. Many
      other treatment options are currently being tested in various other therapeutic
      areas. Some data show clearly that some of these options are now close to
      clinical significance: specific and adapted rehabilitation procedures that will
      include a rationale in patients' care management, use of monoaminergic drugs like
      SSRIs with improvement of motor recovery through a specific action on cortical
      excitability, cortical stimulation or inhibition with magnetic or electric
      techniques with the aim of modifying functional inter cortical balance and
      connections, and clinical and bio markers of recovery that would help to ensure
      appropriate individual care of each patient. Finally, repair therapies with the
      aim of restoring the brain-damaged networks could be useful in patients with
      persistent severe deficits. Several classes are under study for brain repair,
      including the use of stem cells, growth factors, and small molecules, but these
      are still at a preclinical level of development.

PMID- 22865295
TI  - Preoperative CA-125 predicts extra-uterine disease and survival in uterine
      papillary serous carcinoma patients.
AB  - OBJECTIVE: We determined the clinical utility of preoperative serum CA-125 as
      predictor of extra-uterine disease and as prognosticator for survival in patients
      with uterine papillary serous carcinoma (UPSC). METHODS: Patients diagnosed with
      UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement
      were included. A receiver operator characteristic (ROC) curve was used to
      quantify marker performance. Overall and progression free survival were analyzed
      using the Kaplan-Meier method. Regression analyses were used to investigate the
      association of preoperative CA-125 levels and other clinicopathological variables
      with the presence of extra-uterine disease and the effects on survival. RESULTS:
      Sixty-six patients met the study criteria. Using ROC, the CA-125 concentration of
      45 U/mL as cutoff level provided the best sensitivity (75%) and specificity (74%)
      for extra-uterine disease, with a positive predictive value of 86%. Survival was
      significantly longer in patients with preoperative CA-125 <= 45 U/mL (p<0.001).
      Only preoperative CA-125 >45 U/mL remained significantly associated with extra
      uterine disease (OR=6.30, 95% CI 1.93-20.62). Furthermore, advanced FIGO stage
      (HR=4.53, 95% CI 1.50-13.62) and preoperative CA-125 >45 U/mL (HR=3.12, 95% CI
      1.13-8.73) were associated with decreased survival. CONCLUSION: Preoperative
      elevated serum CA-125 is an independent predictor for the presence of extra
      uterine disease and an independent risk factor for survival in UPSC patients.

PMID- 22865296
TI  - Insulin glargine and risk of cancer: a meta-analysis.
AB  - AIMS: Recently, more and more attention has been drawn on the long-term effects
      of insulin glargine. Here we strived to estimate the association of cancer
      occurrence with the use of insulin glargine. METHODS: We searched all the
      publications regarding the association between cancer occurrence and the use of
      insulin glargine using the US National Library of Medicine's PubMed database.
      Data were independently extracted and analyzed using random or fixed effects meta
      analysis depending upon the degree of heterogeneity. RESULTS: Seven cohort
      studies were included in the meta-analysis. Cancer occurrence had no significant
      difference in glargine-treated patients compared to patients treated with other
      insulins (RR=0.86, 95% CI=0.69-1.07, p=0.17, P(heterogeneity)<0.00001). In our
      subgroup analysis, glargine, compared to other insulins, did not increase the
      risk of breast cancer (RR=1.14, 95% CI=0.65-2.02, p=0.65,
      P(heterogeneity)=0.002), prostate cancer (RR=1.00, 95% CI=0.79-1.26, p=0.99,
      P(heterogeneity)=0.78), pancreatic cancer (RR=0.57, 95% CI=0.14-2.35, p=0.44,
      P(heterogeneity)=0.0002) and gastrointestinal cancer (RR=0.80, 95% CI=0.62-1.02,
      p=0.07, P(heterogeneity)=0.86). CONCLUSIONS: This meta-analysis of open-label
      studies does not support an increased cancer risk in patients treated with
      insulin glargine. The result provides confidence for the development of insulin
      glargine, but needs confirmation by further clinical studies.

PMID- 22865297
TI  - Overall evaluation of an immunological latex agglutination system for fecal
      occult blood testing in the colorectal cancer screening program of Florence.
AB  - Several immunological fecal occult blood tests (FOBT) are currently available for
      colorectal cancer (CRC) screening. We compared the HM Jack (Jack) (Kiowa, Japan),
      with the OC-Hemodia (OC) (Eiken, Japan) in use in the Florence screening program.
      Aims of the study were: (i) to investigate the diagnostic performance and the
      best cutoff value for Jack; (ii) to evaluate the handiness of sampling tubes;
      (iii) to compare costs. A total of 5,044 subjects were screened with both tests.
      Sampling tube investigation was performed running each sample on both
      instruments. A number of 352 subjects positive for at least one test (175 OC, 310
      Jack) were selected for further investigations, while 46 subjects refused further
      assessments. Analysis of costs related to the assessment phase was performed on
      the basis of Tuscany region's fares. Amongst the 306 subjects investigated, 9 CRC
      and 67 advanced adenomas (AdA) were detected. Detection rates (DR) were 1.40/00
      for CRC and 9.60/00 for AdA. After Jack cutoff optimization, DR for CRC+AdA
      resulted in 11.10/00 for OC and 13.30/00 for Jack (p=0.041). Sensitivity of the
      methods was 73.7 for OC and 88.2 for Jack; specificity was 97.6 for OC and 96.0
      for Jack, resulting in an increase of the required assessments from 3.5% to 5.1%.
      No differences were observed between sampling methods. Despite the lower
      specificity of Jack, its greater sensitivity makes the method attractive for
      screening programs. An increase of the costs of 30% for every subject
      investigated for pathological lesion (CRC+AdA) may be thus foreseen.

PMID- 22865298
TI  - Importance of chemokine (CC-motif) ligand 2 in breast cancer.
AB  - Breast cancer is the leading cause of cancer-related death in women in the United
      States. Chemokine (CC-motif) ligand 2 (CCL2), an inflammatory cytokine and
      chemokine, is highly expressed within the tumor and stromal cell populations and
      has been associated with enhanced tumorigenesis. In breast cancer patients, CCL2
      has been correlated with high tumor grade and has been shown to have significant
      prognostic value for relapse-free survival. CCL2 likely exerts its pro
      tumorigenic effects through recruitment of tumor-associated macrophages (TAMs);
      TAMs promote a tumorigenic microenvironment through the induction of growth
      enhancers, angiogenic factors and inflammatory mediators. CCL2 may also stimulate
      angiogenesis independently of TAM recruitment as it is closely associated with
      several endothelial cell growth factors. Additionally, CCL2 has been implicated
      in several processes leading to metastatic establishment including the
      development of bone metastasis. It has also been reported to directly upregulate
      pro-tumorigenic inflammatory mediators, including regulated upon activation,
      normal T cell expressed and secreted (RANTES) and tumor necrosis factor-alpha
      (TNF-alpha). While there is emerging support for a tumor promoting role of CCL2
      in breast cancer, additional research is required before CCL2 can be decisively
      established as a prognostic factor and/or treatment target in breast cancer.

PMID- 22865299
TI  - Shorter peripheral blood telomeres are a potential biomarker for patients with
      advanced colorectal adenomas.
AB  - BACKGROUND: Colorectal cancer (CRC) can be prevented by the early detection and
      removal of advanced adenomas (AAs) by colonoscopy. Our aim was to evaluate
      peripheral blood leukocyte (PBL) telomere length as a potential biomarker for the
      presence of AAs. METHODS: PBL telomere length was measured in patients with AAs
      (n=35), in a control group of similarly aged patients who had a normal
      colonoscopy (n=145) and in a separate population group with no history of cancer,
      again similarly aged (n=495). Telomere measurements were performed using a
      quantitative PCR assay and reported as ratios of telomere and single copy gene
      measurements. RESULTS: Telomere lengths tended to be lower in patients with AAs
      than in patients in the normal colonoscopy group (p<0.001) as well as those in
      the population group (p=0.011). A telomere/single copy gene ratio of 0.5 was
      found to have an estimated 94% sensitivity and a 56% specificity for AAs; a
      combination of sensitivity and specificity for which a value of >0.5 would reduce
      the odds of a patient having AAs by a factor of 0.11 (the negative likelihood
      ratio). Thirty three percent of individuals in the population group tested above
      this cutoff and could be considered at low risk for AAs. CONCLUSIONS: PBL
      telomeres are shortened in patients with colorectal neoplasia, suggesting that
      PBL telomere length could be a promising non-invasive blood biomarker to pre
      screen for risk of AAs prior to colonoscopy.

PMID- 22865300
TI  - hMSH2 and hMLH1 gene expression patterns differ between lung adenocarcinoma and
      squamous cell carcinoma: correlation with patient survival and response to
      adjuvant chemotherapy treatment.
AB  - BACKGROUND: We recently showed that the mRNA levels of mismatch repair (MMR)
      proteins in non-small cell lung carcinoma (NSCLC) tissue specimens and the
      phenotypic translation of molecular MMR data refines the biology of the MMR
      system with consequent diagnostic implications in the clinical assessment of lung
      cancer patients. METHODS: hMLH1 and hMSH2 mRNA expression was previously
      evaluated by qPCR for 29 NSCLC patients (13 with squamous cell carcinoma [SQC]
      and 16 with adenocarcinoma [ADC]) and MMR mRNA levels were converted into
      clinically distinct phenotypic entities. In this study, we evaluated the
      correlation of the hMSH2 and hMLH1 mRNA phenotypes with patient survival and
      their response to adjuvant chemotherapy. RESULTS: hMSH2 and hMLH1 mRNA phenotypic
      distribution differed between SQC and ADC. The MMR phenotypes differed also
      between advanced and early stage SQC. SQC patients with an increased hMSH2
      expression had a better outcome than patients with a reduced hMSH2 expression.
      However, ADC patients with an increased hMSH2 expression had a poor outcome
      compared to those with low hMSH2 levels. SQC patients with a high hMSH2
      expression exhibited a better response to adjuvant chemotherapy, whereas ADC
      patients with high hMSH2 levels had a poor response. ADC patients with low hMSH2
      levels showed good response to adjuvant chemotherapy compared to SQC patients
      bearing the same phenotypic profile. CONCLUSIONS: Our findings show that MMR mRNA
      phenotypes may be added to the known biological differences between SQC and ADC.
      hMLH1 and hMSH2 phenotypes distributed differently according to the NSCLC stage.
      Distinct MMR mRNA phenotypes in SQC and ADC corresponded to patient response to
      adjuvant chemotherapy.

PMID- 22865301
TI  - Role of the hematopoietic cytokines SCF, IL-3, GM-CSF and M-CSF in the diagnosis
      of pancreatic and ampullary cancer.
AB  - BACKGROUND: Previous studies have demonstrated altered levels of hematopoietic
      cytokines in the serum of patients with different types of cancer. METHODS: We
      measured the serum levels of the hematopoietic cytokines stem cell factor (SCF),
      interleukin 3 (IL-3), macrophage-colony stimulating factor (M-CSF) and
      granulocyte-macrophage-colony stimulating factor (GM-CSF) in 40 pancreatic and
      ampullary cancer patients and 40 healthy volunteers, using ELISA. We also
      assessed the most widely used pancreatic tumor markers, carbohydrate antigen 19-9
      (CA 19-9) and carcinoembryonic antigen (CEA), in both groups. We then correlated
      the concentrations of the cytokines' and the tumor markers in the patients' serum
      and we estimated their diagnostic ability by calculating diagnostic sensitivity
      and specificity, positive and negative predictive values and the receiver
      operating characteristic (ROC) curve. RESULTS: The SCF and IL-3 levels were
      significantly lower and the M-CSF levels significantly higher in pancreatic
      cancer patients than in controls. There were significant positive correlations
      between the serum levels of CEA and M-CSF, GM-CSF and SCF, and between GM-CSF and
      IL-3. The area under the ROC curve and diagnostic sensitivity of M-CSF were
      greater than those of SCF and IL-3. The diagnostic sensitivity of the combined
      use of SCF and M-CSF reached 97.5%. CONCLUSION: The diagnostic ability of M-CSF
      and SCF in pancreatic and ampullary cancer should stimulate further studies
      evaluating their clinical usefulness as tumor markers.

PMID- 22865302
TI  - Urinary estrogen metabolites and breast cancer: a combined analysis of individual
      level data.
AB  - BACKGROUND: Circulating estrogens are associated with increased breast cancer
      risk, yet the role of estrogen metabolites in breast carcinogenesis remains
      unclear. This combined analysis of 5 published studies evaluates urinary 2
      hydroxyestrone (2-OHE1), 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio
      (2:16alpha-OHE1) in relation to breast cancer risk. METHODS: Primary data on 726
      premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108
      postmenopausal women (385 invasive breast cancer cases and 723 controls) were
      analyzed. Urinary estrogen metabolites were measured using enzyme linked
      immunosorbent assays. Study-specific and combined multivariable adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles
      of estrogen metabolites. Multinomial logistic regression models were fit
      according to hormone receptor status.? RESULTS: Higher premenopausal 2:16alpha
      OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted
      ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-)
      subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16alpha
      OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI:
      0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass
      index (p-interaction=0.003). CONCLUSIONS: Premenopausal urinary 2:16alpha-OHE1
      may play a role in breast carcinogenesis; however, larger studies are needed. Our
      findings do not support reduced breast cancer risk with higher postmenopausal
      2:16alpha-OHE1 overall, although obesity may modify associations with 2-OHE1.

PMID- 22865303
TI  - Disentangling the role of psychopathic traits and externalizing behaviour in
      predicting conduct problems from childhood to adolescence.
AB  - Child and youth conduct problems are known to be a heterogeneous category that
      implies different factors and processes. The current study aims to analyze
      whether the early manifestation of psychopathic traits designates a group of
      children with severe, pervasive and persistent conduct problems. To this end,
      cluster analysis was conducted in a sample of 138 children (27.6 % female), aged
      6-11 at the first wave of the study (T1) and 12-17 in a follow-up carried out 6
      years later (T2). Results allowed the identification of four distinctive
      clusters: Primarily externalizing, Externalizing-psychopathic, Primarily
      psychopathic and Non-problematic. As was expected, the Externalizing-psychopathic
      cluster showed the most severe and persistent pattern of behavioral,
      temperamental and social disruptions across the 6 years of the study. Early
      psychopathic traits seemed also to be relevant in predicting higher levels of
      conduct problems in T2, even when conduct disorders had not manifested in T1.
      These results highlight the role of psychopathic traits in predicting adolescent
      psychosocial disorders and the relevance to analyze them at early developmental
      stages.

PMID- 22865304
TI  - Growth performance in heavy lambs experimentally treated with 17 beta-estradiol.
AB  - European and Italian legislation have banned use of growth promoters in livestock
      since 1988, but epidemiological data show that anabolic drugs are still being
      used illegally. Recent surveys carried out on the cattle farms in Northern Italy
      have confirmed the presence of growth-promoting hormones. Authors report data on
      growth performances in 80 Valle del Belice * Comisana weaned lambs experimentally
      treated with 17 beta-estradiol with 0.5 ml solution of oil Depot Estradiol (r)
      (containing 5 mg of 17beta-estradiol valerate) by intramuscular injection into
      the thigh. The experiment was founded by the National Ministry of Health, to
      validate histological test for surveillance and control of growth-promoting
      hormones in sheep. This study confirmed the strong correlation between clinical
      and anatomopathological features and growth performances of treated animals.
      Otherwise, no significant differences were found on in vivo performance of the
      lambs. Estradiol treatment showed heavier shoulders and necks on treated lambs,
      while the loins were significantly lighter. Moreover, lamb-estradiol-treated
      groups showed lower separable and inseparable fat percentage than lamb-control
      groups.

PMID- 22865305
TI  - Moving to (more) universal health care.

PMID- 22865306
TI  - Comparison of angiographic and IVUS follow-up between the two different drug
      eluting stents implanted simultaneously in the same individuals.
AB  - BACKGROUND: While, theoretically, a drug-eluting stent (DES) with a biodegradable
      polymer should reduce the incidence of late in-stent thrombosis, this has not
      been experimentally tested. OBJECTIVES: This study compared long-term
      manifestations of the Excel DES, with a biodegradable polymer, to the Endeavor
      DES, with a biocompatible polymer, in the same individuals. METHODS: Forty-eight
      patients underwent simultaneous implantation of 1 or more Endeavor stents and 1
      or more Excel stents, during the same procedure, and were evaluated with coronary
      angiography and intravascular ultrasound (IVUS) at least 1 year postprocedure.
      Within-patient comparisons were made between the Excel- and Endeavor-stented
      segments for efficacy and safety. RESULTS: A total of 131 stents (69 Endeavor
      stents and 62 Excel stents) were implanted in 98 lesions among 48 patients.
      Baseline characteristics of the lesions in the two stented segments groups were
      comparable. Average follow-up duration was 14.3 +/- 2.5 months. In-stent late
      luminal loss and luminal stenosis were higher in Endeavor-stented segments than
      in Excel-stented segments (P<.01). The binary restenosis rate was slightly higher
      in Endeavor-stented segments (4.3% vs. 1.6%; P=.379). In-stent thrombosis, late
      incomplete stent apposition, and uncovered stent struts were higher in Excel
      stented segments than in Endeavor-stented segments (P<.01). There was 1 case of
      an in-stent coronary aneurysm with an Excel-stented segment. Four segments, in 4
      cases (2 in each stent group), required target lesion revascularization.
      CONCLUSION: This study suggested that, compared to DESs with a biocompatible
      polymer, DESs with biodegradable polymer do not appear to present an advantage
      for long-term safety.

PMID- 22865307
TI  - Beta-blocker use is not associated with slow flow during rotational atherectomy.
AB  - OBJECTIVES: The purpose of this study was to investigate the association between
      beta-blocker use and slow flow during rotational atherectomy (RA). BACKGROUND: RA
      is often performed as part of percutaneous coronary interventions for the
      treatment of calcified lesions; however, the procedure can be complicated by slow
      flow. Previous reports suggested that the use of beta-blockers was associated
      with slow flow during RA. METHODS: A total of 186 patients who received RA were
      included, and 87 patients were on beta-blockers. The occurrence of slow flow was
      compared between the beta-blocker group (n = 87) and the non-beta-blocker group
      (n = 99). Multivariate logistic regression analysis was performed to investigate
      whether the use of beta-blockers was associated with slow flow. RESULTS: The
      occurrence of slow flow was not different between the beta-blocker group (29.9%)
      and the non-beta-blocker group (24.2%; P=.39). The use of beta-blockers was not
      significantly associated with slow flow (odds ratio, 0.75; 95% confidence
      interval, 0.34-1.68; P=.49) after controlling for all potential confounding
      factors. CONCLUSIONS: There was no definitive association between slow flow and
      the use of beta-blockers during RA. There is no need to discontinue beta-blockers
      in patients receiving RA.

PMID- 22865308
TI  - Vitamin D deficiency, coronary artery disease, and endothelial dysfunction:
      observations from a coronary angiographic study in Indian patients.
AB  - BACKGROUND AND METHODS: Vitamin D deficiency has been linked to an increased risk
      of coronary artery disease (CAD) and cardiovascular (CV) death. Endothelial
      dysfunction plays an important role in pathogenesis of CAD and vitamin D
      deficiency is postulated to promote endothelial dysfunction. Despite rising
      trends of CAD in Asians, only limited data are available on the relationship
      between vitamin D, CAD, and endothelial dysfunction. RESULTS: In a study of 100
      patients undergoing coronary angiography, mean 25(OH)D level was 14.8 +/- 9.1
      ng/mL; vitamin D deficiency was present in 80% and only 7% had optimal 25(OH)D
      levels. Nearly one-third (36%) were severely deficient, with 25(OH)D levels <10
      ng/mL. Those with vitamin D deficiency had significantly higher prevalence of
      double- or triple-vessel CAD (53% vs 38%), diffuse CAD (56% vs 34%), and higher
      number of coronary vessels involved as compared to those with higher 25(OH)D
      levels. Those with lower 25(OH)D levels had significantly lower brachial artery
      flow-mediated dilation (FMD; 4.57% vs 10.68%: P<.001) and significantly higher
      prevalence of impaired FMD (values <4.5%; 50.6% vs 7%; P<.002). A graded
      relationship between 25(OH)D levels and FMD was observed; impaired FMD was noted
      in 62.2%, 38.6%, and 13.3% in those with 25(OH)D levels <10 ng/mL, 10-20 ng/mL,
      and >20 ng/mL, respectively. CONCLUSION: Indian patients with angiographically
      documented CAD frequently have vitamin D deficiency. Patients with lower 25(OH)D
      levels had higher prevalence of double- or triple-vessel CAD and diffuse CAD.
      Endothelial dysfunction as assessed by brachial artery FMD was also more
      frequently observed in those with low 25(OH)D levels.

PMID- 22865309
TI  - Optical coherence tomography analysis of the stenting of saphenous vein graft
      (SOS) Xience V Study: use of the everolimus-eluting stent in saphenous vein graft
      lesions.
AB  - OBJECTIVES: The Stenting of Saphenous Grafts-Xience V (SOS-Xience V) trial
      prospectively examined the frequency of angiographic in-stent restenosis in
      saphenous vein graft (SVG) lesions 12 months after implantation of a Xience V
      everolimus-eluting stent (EES; Abbott Vascular). Optical coherence tomography
      (OCT) during follow-up angiography was added to the protocol after OCT was
      approved for clinical use in the United States. METHODS: Forty patients with 40
      SVG lesions were enrolled in the study, of whom 27 underwent 12-month coronary
      angiography and 12 (only 1 of whom had in-stent restenosis) also had follow-up
      OCT evaluation. OCT strut-level analysis was performed to determine the
      percentage of strut coverage, malapposition, strut protrusion, neointimal
      thickness, and the existence of thrombus. RESULTS: Mean patient age was 67 +/- 7
      years, and 95% were men. A total of 2584 struts were evaluated by OCT. The
      percentages for uncovered, malapposed, and protruding struts were 4%, 9%, and
      15%, respectively. The mean strut neointimal thickness was 0.094 +/- 0.094 mm. Of
      the 12 stents analyzed, 4 (33%) showed full neointimal coverage, 2 (17%) had all
      the struts embedded, 7 (58%) had at least 1 malapposed strut, and 10 (83%) had at
      least 1 protruding strut. The mean difference between the stent area and the
      lumen area was 0.36 +/- 1.6 mm2. No thrombus was detected in the stented areas.
      CONCLUSIONS: Use of EES in SVGs is associated with high rates of stent strut
      coverage and high malapposition rates at 12 months post implantation.

PMID- 22865310
TI  - New re-entry device for revascularization of chronic coronary total occlusions:
      preliminary single Japanese center experience.
AB  - BACKGROUND: Although retrograde approach for coronary chronic total occlusion
      (CTO) has been introduced, the procedure is still time and resource consuming. A
      simplified antegrade approach mightbe another resort. The aim of this study was
      to evaluate a new device designed to facilitate guidewire re-entry into the true
      lumen of a CTO from the adjacent subintimal space. METHODS: Patients with CTO
      were entered into a prospective registry regardless of lesion characteristics. A
      new metal-tip catheter was used initially in primary use cases. If it created
      subintimal tracking, a new re-entry tool (a flat balloon with 2 exit ports offset
      by 180 degrees) was used as a platform to attempt guidewire penetration into the
      distal true lumen. In rescue use cases after unsuccessful conventional wiring,
      the re-entry procedure was subsequently attempted. RESULTS: In 11 CTO lesions
      attempted, device success was achieved in 8 cases (72.7%). Re-entry procedure
      success rate was higher in primary use cases (80%) compared to rescue use cases
      (33.3%). Retrograde approach was conducted immediately after unsuccessful
      antegrade procedure using this device in the other 3 cases and successful
      recanalization was achieved in all cases. All lesions were stented, resulting in
      TIMI 3 flow without major complications. CONCLUSION: A new coronary re-entry
      device may provide another strategic option in the antegrade approach to
      recanalize CTOs.

PMID- 22865311
TI  - Smokers with ST-segment elevation myocardial infarction and short time to
      treatment have equal effects of PCI and fibrinolysis.
AB  - OBJECTIVES: The purpose of this study was to examine the effect of primary
      percutaneous coronary intervention (PCI) compared to fibrinolysis in smokers and
      non-smokers with ST-segment elevation myocardial infarction (STEMI). Smokers seem
      to have less atherosclerosis but are more prone to thrombotic disease. Compared
      to non-smokers, they have higher rates of early, complete reperfusion when
      treated with fibrinolysis for MI. METHODS AND RESULTS: In the Second Danish
      Multicenter Trial in Acute Myocardial Infarction (DANAMI-2), a total of 1572
      patients with STEMI were randomized to either fibrinolysis or PCI (1129 patients
      were enrolled at 24 referral hospitals and 443 patients at 5 invasive treatment
      centers). The primary endpoint for this substudy was death by any cause.
      Secondary endpoints were a composite of death by any cause, clinical re
      infarction or disabling stroke. Follow-up was 3 years. The effect of PCI is
      reported according to time to treatment and smoking status. Data on smoking
      habits were available for 1534 patients (895 smokers and 639 non-smokers).
      Smokers with short time to treatment (<3 hours) benefited equally from PCI and
      fibrinolysis with a trend toward higher mortality in the PCI group (mortality
      [hazard ratio, 1.64 (0.79-3.41); P=.18], composite endpoint [hazard ratio, 1.06
      (0.65-1.71); P=.82]). In non-smokers with short time to treatment PCI was
      superior to fibrinolysis (mortality [hazard ratio, 0.46 (0.22-0.93); P=.02],
      combined endpoint [hazard ratio, 0.45 (0.26- 0.79); P=.004]). Patients with >3
      hours to treatment all showed a tendency toward a superior effect of PCI
      irrespective of smoking habits. CONCLUSIONS: PCI and fibrinolysis are equally
      beneficial in smokers with STEMI and short time to treatment.

PMID- 22865312
TI  - Assessment of inflammatory response to transfemoral transcatheter aortic valve
      implantation compared to transapical and surgical procedures: a pilot study.
AB  - AIMS: Surgical aortic valve replacement (AVR) has been associated with systemic
      inflammatory reactions. Yet, the role of inflammation following transcatheter
      aortic valve implantation (TAVI) has not been fully elucidated. METHODS AND
      RESULTS: In a total of 40 patients evaluated by the 'heart team,' this
      retrospective study assessed levels of high-sensitive C-reactive protein (hs-CRP)
      and leukocyte counts following 'uneventful' AVR and TAVI. Four groups of matched
      patients were compared (AVR; transapical and transfemoral Edwards SAPIEN [TA ES
      and TF ES, respectively]; and transfemoral Medtronic CoreValve [TF CV]). A
      postprocedural increase of both hs-CRP levels and leukocyte counts was observed
      (P<.001) with peak levels 48 hours after the procedures. Comparing treatment
      groups, hs-CRP levels at 48 hours were significantly higher following AVR and TA
      ES compared to TF ES and TF CV (P<.04). Leukocyte counts at 48 hours were higher
      following TA ES compared to TF ES and TF CV (P<.03). Multivariate analysis
      incorporating both hs-CRP levels and leukocyte counts confirmed significant
      differences for all measurements over time (P<.001). Furthermore, the treatment
      group significantly influenced postprocedural hs-CRP levels and leukocyte counts
      (P<.001). CONCLUSION: Both AVR and TAVI evoke a postprocedural inflammatory
      response. Higher hs-CRP levels and leukocyte counts following AVR and apical TAVI
      suggest less inflammation following femoral procedures.

PMID- 22865313
TI  - Randomized comparison of radial versus femoral approach for patients with STEMI
      undergoing early PCI following intravenous thrombolysis.
AB  - BACKGROUND: Early percutaneous coronary intervention (PCI) following thrombolysis
      may be beneficial in patients with ST-segment elevation myocardial infarction
      (STEMI) who were admitted at a non-PCI hospital. The aim of this study was to
      evaluate the safety and efficacy of the radial artery as a vascular route for
      early PCI following thrombolysis in patients with STEMI. METHODS: All consecutive
      STEMI patients within 12 hours after thrombolysis were enrolled, and eligible
      patients were randomly assigned to either transfemoral (TFI group) or transradial
      catheterization (TRI group). Several time intervals were measured. The puncture
      success rate and ambulation time were assessed. The vascular access-site
      complications were also assessed after the PCI procedure, and the incidence of
      major adverse cardiac events (MACE) in hospital was observed. RESULTS: A total of
      119 cases were enrolled, with 60 in the TRI group and 59 in the TFI group. There
      were no significant differences in transfer time and total procedure time. The
      puncture time in the TRI group was not significantly different compared to the
      TFI group. The time between PCI and ambulation in the TRI group was shorter than
      in the TFI group. There was a trend toward lower in the incidence of bleeding
      complications and vascular complications in the TRI group. CONCLUSION: TRI for
      STEMI patients following intravenous thrombolysis was as safe and feasible as
      TFI, with a trend toward lower incidence of bleeding complications and vascular
      complications.

PMID- 22865314
TI  - Cardiac sarcoidosis masquerading as syncope with right ventricular septal mass.
AB  - Cardiac sarcoid remains a challenging diagnostic entity. Electrical abnormalities
      in sarcoid myocarditis range from heart blocks to lethal ventricular
      tachycardias. Sarcoid granulomas have predilection for left ventricular side and
      basal septum in cardiac involvement. We present a case of sarcoid myocarditis
      presenting as mass involving the entire right ventricular side of the
      interventricular septum.

PMID- 22865315
TI  - Transbrachial coil embolization of a giant coronary artery fistula.
AB  - Coronary artery fistulae can present late in adult life. We describe the case of
      a 71-year-old woman who developed a right coronary fistula, which was managed by
      percutaneous transbrachial coil embolization. Complete closure of the fistula was
      confirmed by follow-up angiography at 10 months.

PMID- 22865316
TI  - A novel approach for under-expanded stent: excimer laser in contrast medium.
AB  - The novel approach of using excimer laser in a contrast medium for treating an
      under-expanded stent in a calcified coronary artery is described. In this first
      reported case, the laser in a contrast medium was used to treat an under-expanded
      stent deployed 18 months prior in a calcified non-dilatable coronary artery
      lesion. The normal laser approach in saline medium flush during lasing to clear
      any contrast was not effective. The use of concurrent contrast during lasing was
      effective and successful to help expand the stent with a successful outcome.

PMID- 22865317
TI  - Complex made easy: left anterior descending artery trifurcation lesion completely
      treated with a single device.
AB  - Coronary trifurcation lesions are a complex subset of lesions. We present a case
      of a percutaneous intervention of a trifurcation lesion involving the left
      anterior descending artery and 2 diagonal branches completely treated with one
      single device, the novel stent-on-a-wire (SOAW) (Svelte Medical Systems), for the
      whole procedure. The SOAW is an all-in-one device with a bare cobalt-chrome stent
      mounted on a balloon directly connected to a wire. The stent of the SOAW was
      deployed in the left anterior descending artery over the ostia of the 2 diagonal
      branches. Using the same wire plus balloon device of the SOAW, further recrossing
      in direction of the 2 side branches and balloon dilation of both ostia through
      the stent struts was possible. Conclusive post-dilatation of the stent was then
      performed once again with the same SOAW device. The final angiographic result was
      successful, and patency of the stented segment was confirmed also at 5-month
      angiographic follow-up.

PMID- 22865318
TI  - Longitudinal stent compression is not always a bad event: a case report.
AB  - Ostial left anterior descending artery stent implantation was performed, while
      trying to cross another stent through the left main coronary artery into the left
      circumflex artery the stent was detached from the delivery balloon, subsequently
      jamming the stent of the ostial left anterior descending artery stent. Removing
      the detached stent was possible, but longitudinal compression of the ostial left
      anterior descending artery stent occurred. We finally took advantage of the
      longitudinal compression to advance the equipment into the left circumflex artery
      with good final result.

PMID- 22865319
TI  - Myocardial infarction with acute valvular regurgitation.
AB  - Left-sided valvular lesions are commonly associated with acute and chronic
      coronary syndromes. Ischemic mitral regurgitation is well described in the
      literature. We report a case of acute ischemic right-sided valvular disease in
      which the presenting symptom of an infarction was severe tricuspid regurgitation.
      This rare entity is usually caused by distortion of the valve apparatus due to
      underlying wall motion abnormalities. In conclusion, tricuspid regurgitation is
      an important yet uncommon presentation of acute ischemia that requires a high
      degree of suspicion for diagnosis.

PMID- 22865320
TI  - Treatment of in-stent restenosis involving a bifurcation lesion with a dedicated
      bifurcation device in combination with drug-eluting balloons.
AB  - It can be difficult to find a good treatment strategy in cases with in-stent
      restenosis with involvement of a bifurcation lesion. To avoid multiple stent
      layers and to treat the bifurcation lesion properly, the patient described in
      this case report was treated with a Tryton side branch stent and drug-eluting
      balloons. Angiographic follow-up at 8 months showed an excellent result.

PMID- 22865321
TI  - Percutaneous retrieval of a fractured guide catheter using contralateral snaring.
AB  - Guide catheter kinking and fracture is an uncommon complication of percutaneous
      coronary intervention and may require emergency surgical intervention if
      percutaneous retrieval fails. We present a case of guide catheter kinking and
      fracture during attempts to engage the left main coronary artery in a patient
      with marked iliac tortuosity. The retained guide catheter fragment was retrieved
      percutaneously by using a snare from the contralateral femoral artery and
      removing the "folded-over" catheter fragment through the contralateral
      arteriotomy.

PMID- 22865322
TI  - Surgical retrieval of dislodged stent during transradial coronary intervention.
AB  - Coronary stent dislodgment is a rare but serious complication during percutaneous
      coronary intervention. During transradial coronary intervention, retrieval of a
      dislodged and deformed stent into the guiding catheter is difficult or
      impossible, since a small 6 Fr guiding catheter and sheath system is commonly
      used. I describe a new method to retrieve a dislodged and damaged stent during
      transradial coronary intervention. When a dislodged and unexpanded stent is not
      pulled back completely into the guiding catheter, the damaged stent and guiding
      catheter can be withdrawn together into the radial artery and retrieved
      successfully by radial artery cutdown and repair method.

PMID- 22865323
TI  - Determinants of human papillomavirus (HPV) vaccination intent among three
      Canadian target groups.
AB  - To increase the uptake of the human papillomavirus (HPV) vaccine, understanding
      the determinants of vaccination intentions for various groups is important. Three
      studies examining theoretical determinants of college-aged women's (study 1: n =
      286), parents' of daughters (study 2: n = 230) and parents' of sons (study 3: n =
      137) HPV vaccination intentions were conducted. Participants completed
      questionnaires assessing constructs of protection motivation theory (PMT) and the
      theory of planned behaviour (TPB). Results indicate that both PMT and TPB
      constructs predict intentions for the different groups. Focusing on the response
      efficacy of the vaccine rather than the severity of contracting HPV may be an
      effective way to increase vaccination intentions among all groups. Focusing on
      vulnerability to HPV may only increase intentions among college-aged women and
      parents of sons, and increasing self-efficacy may only increase intentions among
      college-aged women and parents of daughters. Findings have implications for
      understanding differences among groups considering HPV vaccination and tailoring
      interventions.

PMID- 22865324
TI  - Study of KRAS new predictive marker in a clinical laboratory.
AB  - BACKGROUND: The presence of somatic mutations in the KRAS gene has been
      identified as a reliable strong negative predictor for the response to targeting
      the epidermal growth factor receptor (EGFR), in patients with metastatic
      colorectal cancer and the use of anti-EGFR monoclonal antibodies such as
      Cetuximab and Panitumumab is now restricted to patients with no detectable KRAS
      mutations. Between 30 and 40 % of colorectal cancers contain a mutated KRAS
      oncogene. The aim of this study was to evaluate concordance between three methods
      to analyze KRAS mutational status in regard to clinical testing. METHODS: We
      analyzed KRAS mutations in codons 12 and 13 of exon 2 in one hundred formalin
      fixed paraffin-embedded (FFPE) colorectal cancer samples by three different
      methods: Direct Sequencing and two commercial kits on allele-specific
      oligonucleotide hybridization (KRAS StripAssay, Vienna Lab.) and Amplification
      Refractory Mutation System/Scorpions (ARMS/S; TheraScreen KRAS Mutation kit DxS)
      based on q-PCR. RESULTS: We have found similar frequencies of KRAS mutations by
      TheraScreen and Strip-Assay (44 and 48 %), with a kappa value of 0.90, indicating
      almost perfect agreement between methods. The frequency by direct sequencing was
      much lower (26 %) and the kappa values were 0.67 (compared to TheraScreen) and
      0.57 (compared to Strip-Assay) indicating low sensitivity. CONCLUSIONS: On
      analyzing KRAS mutation in FFPE tumor samples, direct sequencing sensitivity is
      too low to be used in a clinical setting. Choosing between ARMS/S; TheraScreen
      KRAS Mutation kit DxS and KRAS StripAssay, Vienna Lab, will depend on laboratory
      facilities and expertise.

PMID- 22865325
TI  - Tumor volume delineation in head and neck cancer with 18-fluor-fluorodeoxiglucose
      positron emission tomography: adaptive thresholding method applied to primary
      tumors and metastatic lymph nodes.
AB  - PURPOSE: There are several potential advantages of using 18-fluor
      fluorodeoxiglucose (18F-FDG) PET for target volume contouring, but before PET
      based gross tumor volumes (GTVs) can reliably and reproducibly be incorporated
      into high-precision radiotherapy planning, operator-independent segmentation
      tools have to be developed and validated. The purpose of the present work was to
      apply the adaptive to the signal/background ratio (R(S/B)) thresholding method
      for head and neck tumor delineation, and compare these GTV(PET) to reference
      GTV(CT) volumes in order to assess discrepancies. MATERIALS AND METHODS: A cohort
      of 19 patients (39 lesions) with a histological diagnosis of head and neck cancer
      who would undergo definitive concurrent radiochemotherapy or radical radiotherapy
      with intensity-modulated radiotherapy technique (IMRT), were enrolled in this
      prospective study. Contouring on PET images was accomplished through standardized
      uptake value (SUV)-threshold definition. The threshold value was adapted to
      R(S/B). To determine the relationship between the threshold and the R(S/B), we
      performed a phantom study. A discrepancy index (DI) between both imaging
      modalities, overlap fraction (OF) and mismatch fraction (MF) were calculated for
      each lesion and imaging modality. RESULTS: The median DI value for lymph nodes
      was 2.67 and 1.76 for primary lesions. The OF values were larger for CT volumes
      than for PET volumes (p < 0.001), for both types of lesions. The MF values were
      smaller for CT volumes than for PET volumes (p < 0.001), for both types of
      lesions. The GTV(PET) coverage (OF(PET)) was strongly correlated with the lesion
      volume (GTV(CT)) for metastatic lymph nodes (Pearson correlation = 0.665; p <
      0.01). For smaller lesions, despite the GTV volumes were relatively larger on PET
      than in CT contours, the coverage was poorer. Accordingly, the MF(PET/CT) was
      negatively correlated with the lesion volume for metastatic lymph nodes.
      CONCLUSIONS: The present study highlights the considerable challenges involved in
      using FDG PET imaging for the delineation of GTV in head and neck neoplasms. The
      methods that rely mainly on SUV(max) for thresholding, as the RS/B method, are
      very sensitive to partial volume effects and may provide unreliable results when
      applied on small lesions.

PMID- 22865326
TI  - Sacral chordoma: management of a rare disease in a tertiary hospital.
AB  - INTRODUCTION: Chordoma is a rare malignant bone tumor. The outcome depends on the
      adequate surgical treatment with complete excision of the tumor with microscopic
      clear margins. MATERIALS AND METHODS: We performed a retrospective review of 13
      cases of chordomas operated in our center between 1988 and 2009. RESULTS: All
      cases were treated with wide excision. Inadequate margins were found in seven
      patients. There were complications in ten patients and long-term sequels in 11
      patients. Nine had recurrence within the first 2 years, six of which had
      inadequate margins. Five had metastatic disease, three of them with inadequate
      margins. During the follow-up, four patients died. In a posterior review, three
      patients survive and all of them had clear margins. CONCLUSIONS: In our
      experience, the best treatment is complete excision of the tumor with clear
      microscopic margins. When this is not possible, local recurrences increase and
      survival rate decreases.

PMID- 22865327
TI  - Lung function predicts mortality: 10-year follow-up after lung cancer screening
      among asbestos-exposed workers.
AB  - PURPOSE: To assess the predictive value of lung function impairment on mortality
      among asbestos-exposed workers. METHODS: A total of 590 workers originally
      screened for occupational lung disease including spirometry and pulmonary
      diffusing capacity measurements were followed up for mortality data (ICD-10
      classification). The mean follow-up time was 10.5 years. Associations of
      different lung function parameters with mortality from all causes and from
      cardiovascular (I00-I99) and non-malignant respiratory diseases (J00-J99) were
      analysed. Factor analysis was used to create obstructive and restrictive factors.
      RESULTS: A total of 191 deaths were found altogether. Most measured lung function
      variables were associated with increased mortality when studied separately. Both
      decreased forced expiratory flow in one second (hazard ratio/measurement unit =
      0.977, 95 % CI 0.969-0.988, p < 0.001) and impaired diffusing capacity (0.973,
      0.965-0.981, p < 0.001) were independently associated with mortality from all
      causes, as well as from cardiovascular and non-malignant respiratory diseases.
      Both obstructive factor alone and the sum of obstructive and restrictive factors
      were associated with all studied mortality categories. The restrictive factor
      alone was associated with all-cause and respiratory mortality. CONCLUSIONS:
      Deteriorated lung function predicts deaths. The reasons for impaired lung
      function should be medically explored to enable restoring measures aiming thus to
      prevent premature deaths.

PMID- 22865328
TI  - A general binomial regression model to estimate standardized risk differences
      from binary response data.
AB  - Estimates of absolute risks and risk differences are necessary for evaluating the
      clinical and population impact of biomedical research findings. We have developed
      a linear-expit regression model (LEXPIT) to incorporate linear and nonlinear risk
      effects to estimate absolute risk from studies of a binary outcome. The LEXPIT is
      a generalization of both the binomial linear and logistic regression models. The
      coefficients of the LEXPIT linear terms estimate adjusted risk differences,
      whereas the exponentiated nonlinear terms estimate residual odds ratios. The
      LEXPIT could be particularly useful for epidemiological studies of risk
      association, where adjustment for multiple confounding variables is common. We
      present a constrained maximum likelihood estimation algorithm that ensures the
      feasibility of risk estimates of the LEXPIT model and describe procedures for
      defining the feasible region of the parameter space, judging convergence, and
      evaluating boundary cases. Simulations demonstrate that the methodology is
      computationally robust and yields feasible, consistent estimators. We applied the
      LEXPIT model to estimate the absolute 5-year risk of cervical precancer or cancer
      associated with different Pap and human papillomavirus test results in 167,171
      women undergoing screening at Kaiser Permanente Northern California. The LEXPIT
      model found an increased risk due to abnormal Pap test in human papillomavirus
      negative that was not detected with logistic regression. Our R package blm
      provides free and easy-to-use software for fitting the LEXPIT model.

PMID- 22865329
TI  - Factors associated with kyphosis progression in older women: 15 years' experience
      in the study of osteoporotic fractures.
AB  - Age-related hyperkyphosis is thought to be a result of underlying vertebral
      fractures, but studies suggest that among the most hyperkyphotic women, only one
      in three have underlying radiographic vertebral fractures. Although commonly
      observed, there is no widely accepted definition of hyperkyphosis in older
      persons, and other than vertebral fracture, no major causes have been identified.
      To identify important correlates of kyphosis and risk factors for its progression
      over time, we conducted a 15-year retrospective cohort study of 1196 women, aged
      65 years and older at baseline (1986 to 1988), from four communities across the
      United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the
      Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs
      obtained at baseline and an average of 3.7 and 15 years later. Repeated measures,
      mixed effects analyses were performed. At baseline, the mean kyphosis angle was
      44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family
      history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density,
      greater body weight, degenerative disc disease, and smoking. Over an average of
      15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent
      determinants of greater kyphosis progression were prevalent and incident
      vertebral fractures, low bone mineral density and concurrent bone density loss,
      low body weight, and concurrent weight loss. Thus, age-related kyphosis
      progression may be best prevented by slowing bone density loss and avoiding
      weight loss.

PMID- 22865330
TI  - Solution NMR and X-ray crystal structures of Pseudomonas syringae Pspto_3016 from
      protein domain family PF04237 (DUF419) adopt a "double wing" DNA binding motif.
AB  - The protein Pspto_3016 is a 117-residue member of the protein domain family
      PF04237 (DUF419), which is to date a functionally uncharacterized family of
      proteins. In this report, we describe the structure of Pspto_3016 from
      Pseudomonas syringae solved by both solution NMR and X-ray crystallography at 2.5
      A resolution. In both cases, the structure of Pspto_3016 adopts a "double wing"
      alpha/beta sandwich fold similar to that of protein YjbR from Escherichia coli
      and to the C-terminal DNA binding domain of the MotA transcription factor (MotCF)
      from T4 bacteriophage, along with other uncharacterized proteins. Pspto_3016 was
      selected by the Protein Structure Initiative of the National Institutes of Health
      and the Northeast Structural Genomics Consortium (NESG ID PsR293).

PMID- 22865331
TI  - Reduction of virulence factor pyocyanin production in multidrug-resistant
      Pseudomonas aeruginosa.
AB  - Nosocomial infections caused by metallo-beta-lactamase (MBL)-producing multidrug
      resistant (MDR) Pseudomonas aeruginosa have become a worldwide problem.
      Pyocyanin, a representative pigment produced by P. aeruginosa, is the major
      virulence factor of this organismThe aim of this study was to investigate the
      pyocyanin-producing ability of MBL-producing MDR P. aeruginosa. A total of 50
      clinical isolates of P. aeruginosa, including 20 MDR strains, were collected at
      18 general hospitals in Japan. The chromaticity and luminosity produced by
      pyocyanin in each isolate were measured. The quantity of pyocyanin and the
      expression of the phzM and phzS genes coding a pyocyanin synthesis enzyme were
      measured. MDR strains showed a bright yellow-green, while non-MDR strains tended
      to show a dark blue-green. The quantities of pyocyanin in MBL-producing strains
      and non-producing strains were 0.015 +/- 0.002 and 0.41 +/- 0.10 MUg,
      respectively. The expression of the phzM and phzS genes in the MDR strains was 11
      and 14 %, respectively, of the expression in the non-MDR strains. When the MBL
      gene was transduced into P. aeruginosa and it acquired multidrug resistance, it
      was shown that the pyocyanin-producing ability decreased. The pathogenicity of
      MBL-producing MDR P. aeruginosa may be lower than that of non-MDR strains. These
      MBL-producing MDR strains may be less pathogenic than non-MDR strains. This may
      explain why MDR-P. aeruginosa is unlikely to cause infection but, rather, causes
      subclinical colonization only.

PMID- 22865332
TI  - Microflora associated with primary endodontic infections: correlations among SEM
      evaluation, clinical features, and radiographic findings.
AB  - The aim of the present study was to characterize, by means of SEM, primary
      endodontic infections and to correlate with clinical and radiographic findings.
      Twelve (12) human extracted teeth (19 roots) presenting primary endodontic
      infection were examined. SEM qualitative observations of bacterial and defense
      cells, their features and distribution within the root canal lumen and root
      dentine were recorded for association with clinical and radiographic tabled data.
      Although a direct correlation between biofilm composition and
      clinical/radiographic findings was not established, structural organization and
      distribution of the biofilm, as well as the characteristics of host response,
      could be easily related to those features. Bacterial biofilm was predominant at
      the apical third. Symptomatic apical periodontitis was related to presence of
      bacterial biofilm all thirds. Defense cells could be seen in the apical third of
      some samples. These cells were present in all thirds in some of the cases with
      open cavities. The correlations performed in this study allowed a better
      understanding of the picture of primary endodontic infection, host response and
      relevant clinical features. The combined use of scanning electron microscopy with
      clinical and radiographic evaluation has the potential to overcome some limits of
      the current knowledge related to pulpal and periapical diseases, providing
      important insights for improving treatment strategies.

PMID- 22865333
TI  - Role of SOCS3 evaluated by immunohistochemical analysis in a cohort of patients
      affected by prostate cancer: preliminary results.
AB  - BACKGROUND: Chronic inflammation may play a role in prostate carcinogenesis.
      Molecular alterations of the Suppressor of Cytokine Signaling (SOCS)-3 can
      contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of
      cancer. Recently, the methylation of SOCS3 gene has been demonstrated to cause
      the non-expression of the protein, being involved in the pathogenesis of prostate
      cancer (PC) and identifying a subset of aggressive tumors. We evaluated the
      expression of SOCS3 protein in patients (pt) with bioptically-diagnosed PC by
      immunohistochemical analysis, which is easier to perform, cheaper and more
      reproducible compared to DNA analysis. METHODS: We analyzed the protein
      expression of SOCS3 by immunohistochemistry in 44 patients (pt) with PC diagnosed
      after biopsy. Slides were incubated with monoclonal antibody SOCS3 (1E4, 1.5
      MUg/mL; Abnova, Taiwan). The SOCS3 staining intensity was evaluated by two
      pathologists (FP and LML) in three different ways: positive (+), negative (-) and
      weak (+/-). Colonic mucosa was used as positive control. 36/44 patients underwent
      radical prostatectomy (RP). RESULTS: Biopsy Gleason score (Gs) was: <7 in 8 pt, 7
      in 33 pt (3 + 4 pattern in 21 pt, 4 + 3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%)
      pt with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt with Gs 7 and
      3/3 (100%) pt with Gs >7 were negative. In 11/33 pt (33%) Gs 7 a weak intensity
      was found so they were classified as SOCS3 +/-.25/36 (69%) patients who underwent
      RP were SOCS3- (15 pt with Gs 7(3 + 4), 7 pt with Gs 7(4 + 3), 3 pt with Gs 8)
      and 11/36 (30%) SOCS3+ (8 pt with Gs 6 and 3 pt with Gs 7(3 + 4)) (Tab 2). 12/25
      (48%) SOCS3- pt had an organ-confined disease (<=pT2), whereas 13/25 (52%) had an
      extra prostatic neoplasm (5 pT3a (one was N+), 6 pT3b, 1 pT4). All SOCS3+
      patients (8/8 (100%)) had an organ-confined disease. 3/3 (100%) SOCS3+/- pt had
      an extra prostatic neoplasm (>pT2). CONCLUSIONS: SOCS3- pt turned out to have a
      more aggressive disease compared with SOCS3+. In particular, also SOCS3+/-
      patients seemed to have an aggressive behavior. The non-expression of SOCS3
      protein may identify PC with more aggressive behavior and can be evaluated with
      immunohystochemical analysis, which is a relatively easy and cheap procedure in
      clinical practice. These results, if confirmed by a wider population and a longer
      follow-up, may encourage the research on the use of this molecular family as a
      prognostic marker and a target for therapy with demethylating agents.

PMID- 22865337
TI  - Molecular diagnostic tools for the detection of nodal micrometastases in prostate
      cancer patients undergoing radical prostatectomy with extended pelvic lymph node
      dissection: a prospective study.
AB  - BACKGROUND: Routine pathological examination can miss micro-metastatic tumor foci
      in the lymph nodes (LN) of patients with prostate cancer (PCa) that undergo
      radical prostatectomy and pelvic lymph node dissection (PLND). The aim of the
      present prospective study was to evaluate the impact of micrometastases assessed
      by serial section (SS), immunohistochemistry (IHC), and Real-time Polymerase
      Chain Reaction (RT-PCR) in patients undergoing radical prostatectomy with
      extended PLND. MATERIALS AND METHODS: 32 consecutive patients who underwent
      radical prostatectomy with extended PLND (obturator, internal/external and distal
      2 cm common iliac lymph-nodes (LN)) for intermediate (clinical T1c-T2 and PSA:10
      20 ng/mL and clinical Gleason Score = 7) or high (clinical stage T3 or PSA>20 or
      clinical Gleason Score = 8-10) PCa were enrolled. The nodes were processed by the
      one uropathologist, both according to the routine pathological examination
      (analysis of the central section for 4 mm nodes or every 2 mm for LN>4 mm), which
      served as comparative method, both according to SS, IHC with antibodies against
      PSA and broad-spectrum Cytokeratins (BSCK), and quantitative RT-PCR targeting
      PSA, PSMA (PS Membrane Antigen), and Glucuronidase-S-Beta (GUSB) mRNA, that are
      over-expressed in prostatic cancer cells. RESULTS: A total of 628 LN were
      analyzed, with a mean number of LN removed of 19.6 (SD = 7.2). Applying the
      routine pathological examination, 10 (31.2%) patients and 23 (3.9%) LN resulted
      positive for nodal involvement, with mean positive LN of 2.2 (SD = 1.4). After
      applying the SS and the molecular method of analysis (IHC and RT-PCR),
      micrometastases were found in 7 LN (SS showed micrometastases in 3 of them, IHC
      in 6 of them and RT-PCR in 7 of them); a total of 3 (9.3%) node-negative patients
      showed micrometastases at routine pathological examination (in 2 patients with RT
      PCR and in 1 with IHC). CONCLUSIONS: The significance of micrometastases in PCa
      and the potential therapeutic role of PLND is not yet clarified, but the
      molecular analysis of the LN can detect a significant percentage of patients who
      harbor micro-metastatic PCa missed at routine pathological examination, and can
      enhance the accuracy of lymphadenectomy as a staging method.

PMID- 22865338
TI  - C library for topological study of the electronic charge density.
AB  - The topological study of the electronic charge density is useful to obtain
      information about the kinds of bonds (ionic or covalent) and the atom charges on
      a molecule or crystal. For this study, it is necessary to calculate, at every
      space point, the electronic density and its electronic density derivatives values
      up to second order. In this work, a grid-based method for these calculations is
      described. The library, implemented for three dimensions, is based on a
      multidimensional Lagrange interpolation in a regular grid; by differentiating the
      resulting polynomial, the gradient vector, the Hessian matrix and the Laplacian
      formulas were obtained for every space point. More complex functions such as the
      Newton-Raphson method (to find the critical points, where the gradient is null)
      and the Cash-Karp Runge-Kutta method (used to make the gradient paths) were
      programmed. As in some crystals, the unit cell has angles different from 90
      degrees , the described library includes linear transformations to correct the
      gradient and Hessian when the grid is distorted (inclined). Functions were also
      developed to handle grid containing files (grd from DMol(r) program, CUBE from
      Gaussian(r) program and CHGCAR from VASP(r) program). Each one of these files
      contains the data for a molecular or crystal electronic property (such as charge
      density, spin density, electrostatic potential, and others) in a three
      dimensional (3D) grid. The library can be adapted to make the topological study
      in any regular 3D grid by modifying the code of these functions.

PMID- 22865340
TI  - New impact factor and Belgian Brain Congress.

PMID- 22865339
TI  - Self-assembled ultra-high aspect ratio silver nanochains.

PMID- 22865341
TI  - Extreme elongation of the thoracic osteophytes in diffuse idiopathic skeletal
      hyperostosis.

PMID- 22865342
TI  - A new strategy for improved glutathione production from Saccharomyces cerevisiae:
      use of cysteine- and glycine-rich chicken feather protein hydrolysate as a new
      cheap substrate.
AB  - BACKGROUND: Glutathione (GSH) is composed of the amino acids glutamic acid,
      cysteine and glycine. This study investigated the usability of chicken feather
      protein hydrolysate (chicken feather peptone, CFP) as a substrate for GSH
      production from Saccharomyces cerevisiae. RESULTS: CFP was found to be rich in
      ash (36.7 g per 100 g), protein (61.1 g per 100 g) and minerals (S, P, K, Ca, Fe,
      Na and Mg). It also had high contents of cysteine and glycine. CFP augmented
      biomass and GSH production by 53 and 115% respectively compared with the control
      medium. The highest biomass (17.4 g l(-1)) and GSH (271 mg L(-1)) concentrations
      were attained in CFP medium. The second highest biomass (16.8 g l(-1)) and GSH
      (255 mg L(-1)) concentrations were obtained in fish peptone medium. It was
      assumed that the high mineral, cysteine and glycine contents of CFP were related
      to cell growth and GSH synthesis in S. cerevisiae. CONCLUSION: This is the first
      report on the effect of cysteine- and glycine-rich protein hydrolysates on GSH
      production from S. cerevisiae. In this regard, CFP was tested for the first time
      as a GSH production substrate. As an additional contribution, a new hydrolysis
      process was developed for the preparation of protein hydrolysates.

PMID- 22865343
TI  - Blaming the messenger for the bad news about partner violence by women: the
      methodological, theoretical, and value basis of the purported invalidity of the
      conflict tactics scales.
AB  - More than 200 studies have found "gender symmetry" in perpetration of violence
      against a marital or dating partner in the sense that about the same percent of
      women as men physically assault a marital or dating partner. Most of these
      studies obtained the data using the Conflict Tactics Scales (CTS). However, these
      results have been challenged by numerous articles in the past 25 years that have
      asserted that the CTS is invalid. This article identifies and responds to 11
      purported methodological problems of the CTS, and two other bases for the belief
      that the CTS is not valid. The discussion argues that the repeated assertion over
      the past 25 years that the CTS is invalid is not primarily about methodology.
      Rather it is primarily about theories and values concerning the results of
      research showing gender symmetry in perpetration. According to the prevailing
      "patriarchal dominance" theory, these results cannot be true and therefore the
      CTS must be invalid. The conclusion suggests that an essential part of the effort
      to prevent and treat violence against women and by women requires taking into
      account the dyadic nature of partner violence through use of instruments such as
      the CTS that measure violence by both partners.

PMID- 22865344
TI  - Airway hemangiomas in PHACE syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To describe the clinical presentation and airway
      characteristics of infants with airway hemangiomas and concomitant PHACE syndrome
      and to determine the prevalence of airway hemangiomas in PHACE subjects at our
      institution. STUDY DESIGN: Case series. METHODS: Retrospective review including
      clinical presentation, airway findings, treatment measures, and outcomes.
      RESULTS: A total of 23 subjects were diagnosed with definite PHACE at our
      institution between September 1, 2005 and September 1, 2011. Twelve (52%) of
      these subjects had documented airway hemangiomas, six of whom were diagnosed and
      treated at our institution. All six subjects underwent direct laryngoscopy and
      bronchoscopy by a pediatric otolaryngologist. Five (83%) subjects had subglottic
      hemangioma. Three subjects (50%) had additional hemangioma within the airway
      located on the epiglottis, vocal folds, posterior pharyngeal wall, and tracheal
      wall. Five subjects (83%) were treated with propranolol, five (83%) were treated
      with systemic steroids, and one subject received vincristine. One subject
      required laser ablation of subglottic hemangioma and tracheotomy. All subjects
      were airway symptom free at last follow-up (average, 35 months; range, 13-76
      months). CONCLUSIONS: Airway hemangiomas can be a life-threatening complication
      of PHACE syndrome. At our institution, 52% of all PHACE subjects were diagnosed
      with airway hemangiomas. Early detection of airway involvement is paramount.
      Given the high rates of airway hemangiomas, we recommend performing direct
      laryngoscopy and bronchoscopy in all PHACE patients with respiratory symptoms. We
      recommend having a low threshold for airway evaluation in asymptomatic PHACE
      patients, especially those who will not be otherwise started on propranolol.

PMID- 22865345
TI  - Bioavailability of metallic impurities in carbon nanotubes is greatly enhanced by
      ultrasonication.
AB  - Metallic impurities within carbon nanotubes (CNTs) are considered as the main
      cause of their toxicity. Ultrasonication is a common procedure used to purify and
      obtain homogeneous dispersions of CNTs as well as to mix them with other
      components for further processing into composites. Herein, the influence of
      ultrasonication upon the bioavailability of metallic impurities in CNTs was
      investigated. We showed that even ultrasonication times as short as 5 min
      significantly enhanced the bioavailability of metallic impurities, which can
      therefore interact more actively with biologically important molecules. These
      findings will have profound impact on the processing of CNTs as well as on
      nanotoxicity studies.

PMID- 22865346
TI  - New insight into the oncogenic mechanism of the retroviral oncoprotein Tax.
AB  - Human T cell leukemia virus type 1 (HTLV-1), an etiological factor that causes
      adult T cell leukemia and lymphoma (ATL), infects over 20 million people
      worldwide. About 1 million of HTLV-1-infected patients develop ATL, a highly
      aggressive non-Hodgkin's lymphoma without an effective therapy. The pX region of
      the HTLV-1 viral genome encodes an oncogenic protein, Tax, which plays a central
      role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling
      pathways and promoting cell cycle progression. Expression of Tax following viral
      entry is critical for promoting survival and proliferation of human T cells and
      is required for initiation of oncogenesis. Tax exhibits diverse functions in host
      cells, and this oncoprotein primarily targets IkappaB kinase complex in the
      cytoplasm, resulting in persistent activation of NF-kappaB and upregulation of
      its responsive gene expressions that are crucial for T cell survival and cell
      cycle progression. We here review recent advances for the pathological roles of
      Tax in modulating IkappaB kinase activity. We also discuss our recent observation
      that Tax connects the IkappaB kinase complex to autophagy pathways. Understanding
      Tax-mediated pathogenesis will provide insights into development of new
      therapeutics in controlling HTLV-1-associated diseases.

PMID- 22865348
TI  - Functional annotation from the genome sequence of the giant panda.
AB  - The giant panda is one of the most critically endangered species due to the
      fragmentation and loss of its habitat. Studying the functions of proteins in this
      animal, especially specific trait-related proteins, is therefore necessary to
      protect the species. In this work, the functions of these proteins were
      investigated using the genome sequence of the giant panda. Data on 21,001
      proteins and their functions were stored in the Giant Panda Protein Database, in
      which the proteins were divided into two groups: 20,179 proteins whose functions
      can be predicted by GeneScan formed the known-function group, whereas 822
      proteins whose functions cannot be predicted by GeneScan comprised the unknown
      function group. For the known-function group, we further classified the proteins
      by molecular function, biological process, cellular component, and tissue
      specificity. For the unknown-function group, we developed a strategy in which the
      proteins were filtered by cross-Blast to identify panda-specific proteins under
      the assumption that proteins related to the panda-specific traits in the unknown
      function group exist. After this filtering procedure, we identified 32 proteins
      (2 of which are membrane proteins) specific to the giant panda genome as compared
      against the dog and horse genomes. Based on their amino acid sequences, these 32
      proteins were further analyzed by functional classification using SVM-Prot, motif
      prediction using MyHits, and interacting protein prediction using the Database of
      Interacting Proteins. Nineteen proteins were predicted to be zinc-binding
      proteins, thus affecting the activities of nucleic acids. The 32 panda-specific
      proteins will be further investigated by structural and functional analysis.

PMID- 22865349
TI  - Social and gender determinants of risk of cryptosporidiosis, an emerging
      zoonosis, in Dagoretti, Nairobi, Kenya.
AB  - The aim of the study was to investigate the social and gender determinants of the
      risk of exposure to Cryptosporidium from urban dairying in Dagoretti, Nairobi.
      Focus group discussions were held in six locations to obtain qualitative
      information on risk of exposure. A repeated cross-sectional descriptive study
      included participatory assessment and household questionnaires (300 randomly
      selected urban dairy farming households and 100 non-dairying neighbours). One
      hundred dairy households randomly selected from the 300 dairy households
      participated in an additional economic survey along with 40 neighbouring non
      dairy households. We found that exposure to Cryptosporidium was influenced by
      gender, age and role in the household. Farm workers and people aged 50 to 65
      years had most contact with cattle, and women had greater contact with raw milk.
      However, children had relatively higher consumption of raw milk than other age
      groups. Adult women had more daily contact with cattle faeces than adult men, and
      older women had more contact than older men. Employees had greater contact with
      cattle than other groups and cattle faeces, and most (77 %) were male. Women took
      more care of sick people and were more at risk from exposure by this route.
      Poverty did not affect the level of exposure to cattle but did decrease
      consumption of milk. There was no significant difference between men and women as
      regards levels of knowledge on symptoms of cryptosporidiosis infections or other
      zoonotic diseases associated with dairy farming. Awareness of cryptosporidiosis
      and its transmission increased significantly with rising levels of education.
      Members of non-dairy households and children under the age of 12 years had
      significantly higher odds of reporting diarrhoea: gender, season and contact with
      cattle or cattle dung were not significantly linked with diarrhoea. In
      conclusion, social and gender factors are important determinants of exposure to
      zoonotic disease in Nairobi.

PMID- 22865347
TI  - Herpesviral infection and Toll-like receptor 2.
AB  - In the last decade, substantial progress has been made in understanding the
      molecular mechanisms involved in the initial host responses to viral infections.
      Herpesviral infections can provoke an inflammatory cytokine response, however,
      the innate pathogen-sensing mechanisms that transduce the signal for this
      response are poorly understood. In recent years, it has become increasingly
      evident that the Toll-like receptors (TLRs), which are germline-encoded pattern
      recognition receptors (PRRs), function as potent sensors for infection. TLRs can
      induce the activation of the innate immunity by recruiting specific intracellular
      adaptor proteins to initiate signaling pathways, which then culminating in
      activation of the nuclear factor kappa B (NF-kappaB) and interferon-regulatory
      factors (IRFs) that control the transcription of genes encoding type I interferon
      (IFN I) and other inflammatory cytokines. Furthermore, activation of innate
      immunity is critical for mounting adaptive immune responses. In parallel, common
      mechanisms used by viruses to counteract TLR-mediated responses or to actively
      subvert these pathways that block recognition and signaling through TLRs for
      their own benefit are emerging. Recent findings have demonstrated that TLR2 plays
      a crucial role in initiating the inflammatory process, and surprisingly that the
      response TLR2 triggers might be overzealous in its attempt to counter the attack
      by the virus. In this review, we summarize and discuss the recent advances about
      the specific role of TLR2 in triggering inflammatory responses in herpesvirus
      infection and the consequences of the alarms raised in the host that they are
      assigned to protect.

PMID- 22865351
TI  - Describing ovarian cycles, pregnancy characteristics, and the use of
      contraception in female white-faced marmosets, Callithrix geoffroyi.
AB  - Endocrine data and characteristics of nonconceptive ovarian cycling and pregnancy
      are limited within the genus Callithrix to the common marmoset (C. jacchus) and
      Wied's black tufted-ear marmoset (C. kuhlii). This article presents patterns of
      urinary pregnanediol-3-glucuronide (PdG) excretion, as determined by enzyme
      immunoassay, throughout the course of ovarian cycling and pregnancy in white
      faced marmosets (C. geoffroyi). Furthermore, characteristics of reproductive
      parameters including litter size, duration of gestation, maternal age, and
      information about ovarian cycling following administration of contraceptives are
      also described. A steep increase in PdG, an indication of ovulation,
      characterizes normative ovarian cycles, with peak-to-peak intervals between
      cycles being 27.82 +/- 1.49 days in length. PdG excretion (MUg/mg Cr) across
      pregnancy peaked during the 1st and 2nd trimesters (1st = 20.71 +/- 2.98, 2nd =
      21.16 +/- 2.60) and declined gradually to near preconception levels over the 3rd
      trimester until parturition (3rd = 5.74 +/- 1.60). Gestation lasted 148.55 +/-
      1.89 days. Most pregnancies (82.8%) resulted in an immediate postpartum ovulation
      (PPO) of 17.45 +/- 2.22 days with 58.3% of PPOs resulting in conception. No
      differences in PdG excretion during the 1st trimester between full pregnancies
      and miscarriages were found, and pregnancy characteristics such as litter size,
      duration of gestation, and maternal age were not associated with PdG
      concentrations. Administration of cloprostenol resulted in shorter peak-to-peak
      cycle durations, but ovulation was detectable with similar concentrations of peak
      PdG to a normal nonconceptive cycle. Conversely, medroxyprogesterone acetate
      (DMPA) injections resulted in little to no PdG excretion across the ovarian
      cycle. Both methods of contraception providing effective prevention of
      conception. Overall, these results show that strong similarities in reproductive
      parameters persist within the genus Callithrix and to a lesser extent across the
      Callitrichidae family.

PMID- 22865353
TI  - Imaging in neonatal maple syrup urine disease.

PMID- 22865352
TI  - Increased fracture risk assessed by fracture risk assessment tool in Greek
      patients with Crohn's disease.
AB  - BACKGROUND: The World Health Organization has recently developed the fracture
      risk assessment tool (FRAX) based on clinical risk factors and bone mineral
      density (BMD) for evaluation of the 10-year probability of a hip or a major
      osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX
      tool in Greek patients with inflammatory bowel disease (IBD). METHODS: FRAX
      scores were applied to 134 IBD patients [68 Crohn's disease (CD); 66 ulcerative
      colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral
      neck and lumbar spine during the period 2007-2012. Calculation of the FRAX
      scores, with or without BMD, was made through a web-based probability model used
      to compute individual fracture probabilities according to specific clinical risk
      factors. RESULTS: The median 10-year probability of a major osteoporotic fracture
      for IBD patients based on clinical data was 7.1%, and including the BMD was 6.2%.
      A significant overestimation with the first method was found (P = 0.01). Both
      scores with and without BMD were significantly higher in CD patients compared
      with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year
      probability of hip fracture based on clinical data was 0.8%, and including the
      BMD was 0.9%. The score with use of BMD was significantly higher in CD compared
      with UC patients (P = 0.04). CONCLUSIONS: CD patients have significantly higher
      FRAX scores and possibly fracture risk compared with UC patients. The clinical
      FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek
      IBD patients.

PMID- 22865354
TI  - Serum 17 alpha hydroxyprogesterone in normal full term and preterm vs sick
      preterm and full term newborns in a tertiary hospital.
AB  - OBJECTIVES: To determine the variables affecting serum 17 hydroxyprogesterone
      (17OHP) in neonates born at a tertiary hospital in Mumbai, India. METHODS: Serum
      17OHP was measured in peripheral venous blood between 3rd to 5th day of life by
      competitive radioimmunoassay and on follow up at 3 mo of age. Serum 17OHP was
      compared among four groups [full term healthy(FT), full term stressed(FS),
      preterm healthy(PT), preterm stressed(PS)] by non-parametric tests (Kruskal
      Wallis (KW) test and Mann- Whitney (MW) test). Pearson's test was used to
      correlate natural log of serum 17OHP (ln17OHP) with variables like gestational
      age, birth weight, stress factor, sex, antenatal administration of
      glucocorticoids to mothers, Apgar score at 5 min and mode of delivery. Linear
      regression analysis was done using significant variables in Pearson's test to
      determine best predictors of ln17OHP. RESULTS: The initial median (number of
      cases, inter-quartile range) serum 17OHP (ng/ml) for the four groups was as
      follows; FT 8.4 (33, 6-13); PT 20 (36, 11-29.5); FS 34 (29, 26-45) and PS 58 (24,
      40.75-76.5) [total N = 122 newborns, p = 0.001]. Pearson's test showed that
      gestational age, birth weight, stress factor, Apgar score were negatively
      correlated with 17OHP whereas stress factor, mode of delivery, use of antenatal
      steroids in mothers were significantly positively correlated. However, stress
      factor emerged as the most important significant positive predictor (multiple R =
      0.643, P = <0.0001). On follow up at 3 mo age, the median 17OHP (N = 73 newborns)
      had significantly decreased to normal level. CONCLUSION: Stress due to neonatal
      illnesses like meconium aspiration, sepsis, birth asphyxia, etc. significantly
      elevate serum 17OHP and may lead to false positives in newborn screening for
      congenital adrenal hyperplasia.

PMID- 22865355
TI  - Thrombocytopenia in an infant.

PMID- 22865356
TI  - Intimate partner violence prevention program in an Asian immigrant community:
      integrating theories, data, and community.
AB  - To fill an existing gap in research and practice on intimate partner violence
      (IPV) in immigrant communities, the authors developed an IPV prevention program,
      called the Shanti Project, in an Asian Indian community in the Midwest. Building
      on the notion of shanti (harmony/peace), a cherished value and strength of the
      community, we created a communications campaign that combined social marketing
      and community-based participatory approaches. Recognizing the interactive
      influences of multiple levels of social ecology, campaign activities were
      designed to bring about changes at the individual, relationship/family,
      organization, and community levels. This article presents the development of this
      theoretically, empirically, and community-based IPV prevention program.

PMID- 22865357
TI  - Hexavalent chromium and its effect on health: possible protective role of garlic
      (Allium sativum Linn).
AB  - Hexavalent chromium or chromium (VI) is a powerful epithelial irritant and a
      confirmed human carcinogen. This heavy metal is toxic to many plants, aquatic
      animals, and bacteria. Chromium (VI) which consists of 10%-15% total chromium
      usage, is principally used for metal plating (H2Cr2O7), as dyes, paint pigments,
      and leather tanning, etc. Industrial production of chromium (II) and (III)
      compounds are also available but in small amounts as compared to chromium (VI).
      Chromium (VI) can act as an oxidant directly on the skin surface or it can be
      absorbed through the skin, especially if the skin surface is damaged. The
      prooxidative effects of chromium (VI) inhibit antioxidant enzymes and deplete
      intracellular glutathione in living systems and act as hematotoxic, immunotoxic,
      hepatotoxic, pulmonary toxic, and nephrotoxic agents. In this review, we
      particularly address the hexavalent chromium-induced generation of reactive
      oxygen species and increased lipid peroxidation in humans and animals, and the
      possible role of garlic (Allium sativum Linn) as a protective antioxidant.

PMID- 22865358
TI  - Antioxidative and hypolipidemic efficacy of alcoholic seed extract of Swietenia
      macrophylla in streptozotocin diabetic rats.
AB  - The present study was designed to examine the antioxidative potential and
      antihyperlipidemic activity of Swietenia macrophylla in streptozotocin diabetic
      rats. The experimental groups were rendered diabetic by intraperitoneal injection
      of a single dose of streptozotocin (STZ; 40 mg/kg body weight, BW). Rats with
      glucose levels >200 mg/dL were considered diabetic and were divided into five
      groups. Three groups of diabetic animals were orally administered daily with seed
      extract (SME) at a dosage of 50, 100 and 200 mg/kg BW. One group of STZ rats was
      treated as diabetic control and another group orally administered 600 MUg/kg BW
      glibenclamide daily. Repeated daily oral administration of S. macrophylla
      significantly reduced blood glucose levels after 45 days of treatment. The lipid
      peroxidation products such as thiobarbituric acid reactive substances and lipid
      hydroperoxides of SME treated rats decreased in the plasma, liver and kidney.
      Glutathione peroxidase, superoxide dismutase and catalase activity were
      significantly increased in SME treated rats. Antioxidants such as reduced
      glutathione level in the plasma, liver and kidney and vitamins C and E levels in
      the plasma increased in SME treated rats. Total cholesterol, triglycerides,
      phospholipids and free fatty acids and lipoproteins levels increased. Altered
      lipid profile of treated rats lead to normality with treatment of S. macrophylla.
      Thus, our results indicate that the administration of 100 mg/kg BW SME restores
      near normal blood glucose, redox status and lipid profile in STZ-diabetic rats.

PMID- 22865359
TI  - Histological alterations in the ultimobranchial gland of teleost Heteropneustes
      fossilis in response to chlorpyrifos treatment.
AB  - In this study, an experiment was performed on Heteropneustes fossilis for short
      term (1.76 mg/L chlorpyrifos, i.e., 0.8 of 96-h LC50) and long-term (0.44 mg/L
      chlorpyrifos, i.e., 0.2 of 96-h LC50) exposure. The fish were sacrificed after
      24, 48, 72 and 96 h in the short-term experiment and after 7, 14, 21 and 28 days
      in the long-term experiment. On these intervals, blood was collected and analysis
      of serum calcium was done. Ultimobranchial glands were also fixed for
      histological study. The serum calcium levels of H. fossilis exhibit a decline
      after 24 h following exposure to chlorpyrifos. This decrease continues until the
      end of the experiment (96 h). The serum calcium levels of chronically exposed
      fish exhibit a decrease on day 7. Thereafter, the levels continue to fall
      progressively until the end of the experiment (28 days). The ultimobranchial
      gland of chlorpyrifos treated fish exhibits no histological change up to 48 h.
      After 72 h, there is a decrease in the staining response of cytoplasm of the
      ultimobranchial cells. The nuclear volume of these cells is slightly decreased.
      After 96 h following chlorpyrifos exposure, these changes become exaggerated. In
      chlorpyrifos-treated fish there is no change in the histological structure of the
      ultimobranchial gland up to 14 days. After 21 days, the cytoplasm of
      ultimobranchial cells stain feebly and the nuclear volume of these cells exhibits
      a decrease. Following 28 days treatment, the nuclear volume of these cells
      records a further decrease and the gland depicts vacuolization and degeneration
      at certain areas.

PMID- 22865360
TI  - Treatment with tetrahydrocannabinol (THC) prevents infertility in male cystic
      fibrosis mice.
AB  - BACKGROUND: Cystic fibrosis (CF) is a hereditary disease caused by mutations of
      the gene encoding a channel protein CFTR, conducting Cl- and HCO3 - ions. The
      disease is characterized by disturbances in most physiological systems, and more
      than 95% of men are infertile. The mechanism underlying the etiology of CF is
      associated with an imbalance of fatty acids. It has been suggested that the
      function of the endocannabinoid system is also disturbed in CF, because
      endocannabinoids are derivatives of fatty acids. We assumed, therefore, that
      endocannabinoid activity, which plays an important role in fertility, is
      disrupted in CF and could be one of the causes of infertility. The aim of the
      present study was to test the hypothesis that stimulation of endocannabinoid
      receptors in infancy would normalize their function and prevent infertility in
      adulthood. METHODS: Knockout male mice (cftr-/-) were treated with
      tetrahydrocannabinol (THC), endocannabinoid receptors agonist, in infancy from
      days 7 until 28, daily. RESULTS: CF males treated with THC were fully fertile,
      producing offspring comparable by the number of litters and the number of pups
      with wild-type mice. CF males that were not treated with THC were completely
      infertile. CONCLUSIONS: The present study shows that (i) endocannabinoid function
      is impaired in CF mice, as evidenced by the regenerating effect of its
      stimulation on the fertility of otherwise infertile males, (ii) endocannabinoid
      system dysfunction is apparently the determining factor causing infertility in
      CF, and (iii) mild stimulation of the endocannabinoid system in infancy and
      adolescence appears to normalize many reproductive processes and thereby prevent
      infertility in CF males.

PMID- 22865361
TI  - Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid
      treatment in infancy.
AB  - Substantial data have been accumulated regarding the molecular basis of cystic
      fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on
      brain processes has been the focus of much less attention. We have studied some
      behavioral parameters, such as motor activity and anxiety level, in a mice model
      of CF. We have assumed that functioning of the endocannabinoid system could be
      impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid
      deficiency is considered a major factor in CF etiology). We have suggested that
      chronic treatment with cannabinoid receptors agonist during infancy would balance
      cannabinoid levels and prevent CF-related behavioral alterations. Motor activity
      and anxiety level were studied in naive adult CF mice (cftr-deficient mice) and
      compared with wild-type mice and to CF mice treated chronically with Delta9
      tetrahydrocannabinol (Delta9-THC; endocannabinoid receptor agonist) during
      infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level
      of anxiety in the plus maze, a month after cessation of treatment. Motor activity
      decrease and elevated anxiety level were found in adult naive CF mice compared
      with wild-type mice. CF mice treated with THC in infancy showed normal motor
      activity and anxiety levels in adulthood. Motor function alteration and elevated
      anxiety levels in CF can result from lack of CFTR-channel in neurons and
      disturbed activity of various brain areas, as well as being secondary and
      mediated by fatty acids deficiency, altered levels of endocannabinoids and their
      receptors. It can be suggested that chronic treatment during infancy restores
      endocannabinoid function and thus prevents behavioral alterations.

PMID- 22865362
TI  - Anti-inflammatory and analgesic properties of the ethanolic extract of
      Cnidoscolus aconitifolius in rats and mice.
AB  - BACKGROUND: Ethanolic leaf extract of Cnidoscolus aconitifolius was evaluated for
      analgesic and anti-inflammatory activities. METHODS: The analgesic activity of
      the extract was assayed by the formalin-induced paw licking test, acetic acid
      induced abdominal writhing and hot plate test, whereas its anti-inflammatory
      activity was determined by its effects on carrageenan-induced paw edema. RESULTS:
      The extract of C. aconitifolius prolonged the reaction time of mice to pain in a
      dose-dependent manner. The optimal analgesic effect of the extract was obtained
      when the extract was administered 90 min before pain stimulation in the hot plate
      test. The extract of C. aconitifolius (100 or 200 mg/kg b.w.) inhibited acetic
      acid-induced irritation of paws of rats comparably with that of indomethacin (10
      mg/kg b.w.) and had significantly lower mean number of lickings of paws than the
      control rats (p<0.05). Carrageenan-induced edema was markedly inhibited (p<0.05)
      by the extracts (100 and 200 mg/kg b.w.) when compared with control rats.
      Inhibition of writhing movement in rats administered with the extract was lower
      (p<0.05) than rats administered with indomethacin but its effect was dose
      dependent. CONCLUSIONS: Our investigations show that C. aconitifolius possesses
      significant anti-inflammatory and analgesic activities that should be explored.

PMID- 22865363
TI  - Birth month and longevity - monthly birth distribution in acute coronary events
      provoked by atherothrombosis in patients treated with percutaneous coronary
      intervention (PCI).
AB  - BACKGROUND: Human homeostasis is time related. Environmental physical factors
      also play a role. Recent studies published by the National Academy of Sciences
      (USA) describe human longevity links with the month of birth. The aim of this
      study was to check monthly birth distribution in patients undergoing percutaneous
      coronary intervention (PCI) for acute myocardial infarction (AMI) related to
      atherothrombosis - one of the main causes of morbidity and mortality in the
      industrial world. METHODS: A total of 4732 (3594 men) subjects were included in
      the study. Patients treated with PCI for AMI in the years 2000 to March 2010 were
      studied. The population registry specific to 1950 excluded 1024 patients, i.e.,
      those registered as born on January 1 and they were replaced with patients with
      an average of births from January 2 to 31. A total of 3675 patients were finally
      studied (2839 men, 836 women). RESULTS: The average monthly birth number was
      306+/-60.38. Significant monthly differences in birth number (q2=21.077, p<0.03)
      were observed. A higher birth rate in the first four months of the year was
      revealed, with the exception of February. The number of births in these months
      exceeded the following two four-month data (q2=20.57, p<0.024). March births
      exceeded the monthly average by more than two standard deviations (SD) - 462,
      with an analogical increase for both genders. In May-December births were below
      average. CONCLUSIONS: Patients with AMI treated with PCI show differences in the
      month of birth with the majority being born in the first four months of the year
      and of those most were born in March. Possible implications on pathogenetic clues
      of atherothrombosis can be assumed.

PMID- 22865364
TI  - Effect of graded doses of Caesalpinia bonducella seed extract on ovary and uterus
      in albino rats.
AB  - Histological changes observed under light microscope illustrate follicular
      degeneration in ovary, vacuolation and mild disorganization of uterus on
      treatment with graded doses of alcohol seed extract of Caesalpinia bonducella.
      There was a significant decrease (p<=0.05) in duration of estrous cycle and mean
      ovarian weight. However, there were no uniform variations in mean uterine weight,
      serum estradiol and progesterone level. The results suggest that alcohol seed
      extract of C. bonducella has antiestrogenic property, possibly acting via
      inhibition of estrogen secretion.

PMID- 22865365
TI  - How specific is the learning in an auditory frequency discrimination task?
AB  - BACKGROUND: There is ample evidence showing that frequency discrimination can
      dramatically improve with practice. Nevertheless, the ability to generalize the
      learning gains to conditions that were not encountered during training is still
      controversial. Therefore, the purpose of the present study was to evaluate the
      extent of generalization to the untrained ear, to an untrained frequency (2000
      Hz) and to an untrained (noisy) environment by continuing to train the
      generalization conditions. METHODS: Twenty-one participants took part in two
      training phases. The first training phase included nine training sessions that
      consisted each of six threshold measurements of difference limen for frequency
      (DLF) at 1000 Hz, and a 10th testing session that consisted of three DLF
      thresholds at 1000 Hz. The generalization phase included four training sessions
      that consisted each of six DLF threshold estimates, two days at each
      generalization condition (each participant was trained in two out of three
      generalization conditions, thus the total number of participants trained in each
      generalization condition was 14). All DLF thresholds were estimated using a three
      interval, two-alternative forced choice adaptive procedure. RESULTS: Results
      showed that (1) the initial thresholds in the generalization conditions were
      reduced following training, and (2) new learning was observed in the subsequent
      training sessions suggesting that the learning was partially specific to the
      trained ear, frequency and environment. CONCLUSIONS: These results have important
      theoretical and clinical implications regarding the extent of the plasticity of
      the auditory system and the neural processes that underlie this plasticity.

PMID- 22865366
TI  - Absence of herpes virus entry mediator (HVEM) increases bone mass by attenuating
      receptor activator of nuclear factor-kappaB ligand (RANKL)-induced
      osteoclastogenesis.
AB  - Herpes virus entry mediator (HVEM), which is constitutively expressed at a high
      level on myeloid lineage cells, is also expressed on bone marrow-derived
      macrophages, suggesting that it may play a role in bone metabolism by affecting
      osteoclasts (OC) derived from bone marrow-derived macrophages. To address this
      question, we evaluated bone mass by micro-computed tomography and the number and
      activity of OC by tartrate-resistant acid phosphatase (TRAP) and pit formation on
      dentine slices, comparing HVEM-knockout mice with wild-type mice. The absence of
      HVEM led to a higher bone mass and to decreased levels of serum collagen type I
      fragments and serum TRACP5b in vivo. In vitro HVEM deficiency resulted in a
      reduced number and activity of OC and an impaired receptor activator of nuclear
      factor-kappaB ligand signaling through reduced activation of nuclear factor
      kappaB and of nuclear factor of activated T-cells cytoplasmic 1. Exogenous
      soluble HVEM decreased expression of TRAP, whereas soluble LIGHT (a ligand of
      HVEM) increased it, indicating the occurrence of a positive signaling through
      HVEM during osteoclastogenesis. Our findings indicate that HVEM regulates bone
      remodeling via action on OC. The higher bone mass in the femurs of HVEM-knockout
      mice could be, at least in part, due to attenuated osteoclastogenesis and bone
      resorption resulting from decreased receptor activator of nuclear factor-kappaB
      ligand signaling in the OC.

PMID- 22865367
TI  - The organizational and aromatization hypotheses apply to rapid, nonclassical
      hormone action: neonatal masculinization eliminates rapid estradiol action in
      female hippocampal neurons.
AB  - Early exposure to the steroid sex hormone testosterone and its estrogen
      metabolite estradiol masculinize neural tissue during a developmental critical
      period. Many aspects of neuron anatomy and physiology are permanently altered,
      including later sensitivity to estradiol. Although it is well established that
      early hormone exposure alters neuronal responsiveness regarding classical
      estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet
      been determined whether it also alters neuronal processing of nonclassical
      estrogen receptor signaling, including the actions of membrane-associated
      estrogen receptors. Hence, we tested whether membrane estrogen receptor
      regulation of cAMP response element binding protein (CREB) phosphorylation
      observed in female (but not male) hippocampal pyramidal neurons is due to the
      lack of androgen and/or estrogen exposure in females during this critical period.
      Female rat neonates on postnatal d 0 and 1 were systemically injected with one of
      four compounds: vehicle, testosterone, the nonaromatizable androgen
      dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron
      cultures were generated from these animals. After 8-9 d in culture, we assessed
      whether estradiol affected CREB phosphorylation. Neurons from female neonates
      exposed to testosterone lacked estradiol signaling to CREB. In contrast,
      dihydrotestosterone injections of female neonates did not disrupt estradiol
      regulation of CREB. Estradiol injections of female neonates, however, eliminated
      estradiol signaling to CREB. These findings indicate that testosterone
      aromatization to estradiol leads to a masculinization/defeminization process
      whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB.
      Broadly, these findings extend the organizational and aromatization hypotheses to
      rapid, nonclassical hormone action.

PMID- 22865368
TI  - DNA methylation and histone modifications are associated with repression of the
      inhibin alpha promoter in the rat corpus luteum.
AB  - The transition from follicle to corpus luteum after ovulation is associated with
      profound morphological and functional changes and is accompanied by corresponding
      changes in gene expression. The gene encoding the alpha subunit of the dimeric
      reproductive hormone inhibin is maximally expressed in the granulosa cells of the
      preovulatory follicle, is rapidly repressed by the ovulatory LH surge, and is
      expressed at only very low levels in the corpus luteum. Although previous studies
      have identified transient repressors of inhibin alpha gene transcription, little
      is known about how this repression is maintained in the corpus luteum. This study
      examines the role of epigenetic changes, including DNA methylation and histone
      modification, in silencing of inhibin alpha gene expression. Bisulfite sequencing
      reveals that methylation of the inhibin alpha proximal promoter is low in
      preovulatory and ovulatory follicles but is elevated in the corpus luteum.
      Increased methylation during luteinization is observed within the cAMP response
      element in the promoter, and EMSA demonstrate that methylation of this site
      inhibits cAMP response element binding protein binding in vitro. Chromatin
      immunoprecipitation reveals that repressive histone marks H3K9 and H3K27
      trimethylation are increased on the inhibin alpha promoter in primary luteal
      cells, whereas the activation mark H3K4 trimethylation is decreased. The changes
      in histone modification precede the alterations in DNA methylation, suggesting
      that they facilitate the recruitment of DNA methyltransferases. We show that the
      DNA methyltransferase DNMT3a is present in the ovary and in luteal cells when the
      inhibin alpha promoter becomes methylated and observe recruitment of DNMT3a to
      the inhibin promoter during luteinization.

PMID- 22865369
TI  - Direct activation of Xenopus iodotyrosine deiodinase by thyroid hormone receptor
      in the remodeling intestine during amphibian metamorphosis.
AB  - Thyroid hormone (TH) plays critical roles during vertebrate postembryonic
      development. TH production in the thyroid involves incorporating inorganic iodide
      into thyroglobulin. The expression of iodotyrosine deiodinase (IYD; also known as
      iodotyrosine dehalogenase 1) in the thyroid gland ensures efficient recycling of
      iodine from the byproducts of TH biosynthesis: 3'-monoiodotyrosine and 3', 5'
      diiodotyrosine. Interestingly, IYD is known to be expressed in other organs in
      adult mammals, suggesting iodine recycling outside the thyroid. On the other
      hand, the developmental role of iodine recycling has yet to be investigated.
      Here, using intestinal metamorphosis as a model, we discovered that the Xenopus
      tropicalis IYD gene is strongly up-regulated by TH during metamorphosis in the
      intestine but not the tail. We further demonstrated that this induction was one
      of the earliest events during intestinal metamorphosis, with IYD being activated
      directly through the binding of liganded TH receptors to a TH response element in
      the IYD promoter region. Because iodide is mainly taken up from the diet in the
      intestine and the tadpole stops feeding during metamorphosis when the intestine
      is being remodeled, our findings suggest that IYD transcription is activated by
      liganded TH receptors early during intestinal remodeling to ensure efficient
      iodine recycling at the climax of metamorphosis when highest levels of TH are
      needed for the proper transformations of different organs.

PMID- 22865371
TI  - Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through
      divergent signaling pathways in cultured human placental trophoblasts.
AB  - CRH and its related peptides urocortins (UCN) have been identified in placenta
      and implicated to play pivotal roles in the regulation of pregnancy and
      parturition in humans. The objectives of present study were to investigate the
      effects of endogenous CRH and its related peptides in the regulation of steroid
      production in placenta. Placental trophoblasts were isolated from term placenta
      tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents
      in culture media were determined by radioimmunoassay. Treatment of cultured
      trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased
      P(4) production. Treatment of cells with CRH receptor type 1 antagonist
      antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased
      E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2
      cells showed a decrease in E(2) production and an increase in P(4) production. In
      CRH-R2 knockdown cells, CRH stimulated GTP-bound Galphas protein and
      phosphorylated phospholipase C-beta3. Adenylyl cyclase and protein kinase A
      inhibitors blocked CRH-induced increased E(2) production but not decreased P(4)
      production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine
      blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells.
      UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Galphai protein and
      phosphorylated phospholipase C-beta3 expression. Both U73122 and chelerythrine
      blocked UCNIII-induced increased E(2) production and decreased P(4) production.
      We suggest that CRH and its related peptides might be involved in changes in the
      progesterone to estrogen ratio during human pregnancy.

PMID- 22865370
TI  - Ablation of leptin signaling to somatotropes: changes in metabolic factors that
      cause obesity.
AB  - Mice with somatotrope-specific deletion of the Janus kinase binding site in
      leptin receptors are GH deficient as young adults and become obese by 6 months of
      age. This study focused on the metabolic status of young (3-4.5 month old)
      preobese mutant mice. These mutants had normal body weights, lean body mass,
      serum leptin, glucose, and triglycerides. Mutant males and females showed
      significantly higher respiratory quotients (RQ) and lower energy output,
      resulting from a higher volume of CO(2) output and lower volume of O(2)
      consumption. Deletion mutant females were significantly less active than
      controls; they had higher levels of total serum ghrelin and ate more food. Mutant
      females also had lower serum insulin and higher glucagon. In contrast, deletion
      mutant males were not hyperphagic, but they were more active and spent less time
      sleeping. Adiponectin and resistin, both products of adipocytes, were increased
      in male and female mutant mice. In addition, mutant males showed an increase in
      circulating levels of the potent lipogenic hormone, glucose-dependent
      insulinotropic peptide. Taken together, these results indicate that mutant mice
      may become obese due to a reduction in lipid oxidation and energy expenditure.
      This may stem from GH deficiency. Reduced fat oxidation and enhanced insulin
      sensitivity (in females) are directly related to GH deficiency in mutant mice
      because GH has been shown by others to increase insulin sensitivity and fat
      oxidation and reduce carbohydrate oxidation. Gender-dependent alterations in
      metabolic signals may further exacerbate the future obese phenotype and affect
      the timing of its onset. Females show a delay in onset of obesity, perhaps
      because of their low serum insulin, which is lipogenic, whereas young males
      already have higher levels of the lipogenic hormone, glucose-dependent
      insulinotropic peptide. These findings signify that leptin signals to
      somatotropes are vital for the normal metabolic activity needed to optimize body
      composition.

PMID- 22865372
TI  - Acylation type determines ghrelin's effects on energy homeostasis in rodents.
AB  - Ghrelin is a gastrointestinal polypeptide that acts through the ghrelin receptor
      (GHSR) to promote food intake and increase adiposity. Activation of GHSR requires
      the presence of a fatty-acid (FA) side chain on amino acid residue serine 3 of
      the ghrelin molecule. However, little is known about the role that the type of FA
      used for acylation plays in the biological action of ghrelin. We therefore
      evaluated a series of differentially acylated peptides to determine whether
      alterations in length or stability of the FA side chain have an impact on the
      ability of ghrelin to activate GHSR in vitro or to differentially alter food
      intake, body weight, and body composition in vivo. Fatty acids principally
      available in the diet (such as palmitate C16) and therefore representing
      potential substrates for the ghrelin-activating enzyme ghrelin O-acyltransferase
      (GOAT) were used for dose-, time-, and administration/route-dependent effects of
      ghrelin on food intake, body weight, and body composition in rats and mice. Our
      data demonstrate that altering the length of the FA side chain of ghrelin results
      in the differential activation of GHSR. Additionally, we found that acylation of
      ghrelin with a long-chain FA (C16) delays the acute central stimulation of food
      intake. Lastly, we found that, depending on acylation length, systemic and
      central chronic actions of ghrelin on adiposity can be enhanced or reduced.
      Together our data suggest that modification of the FA side-chain length can be a
      novel approach to modulate the efficacy of pharmacologically administered
      ghrelin.

PMID- 22865373
TI  - Identification, proliferation, and differentiation of adult Leydig stem cells.
AB  - Leydig cells, the testosterone-producing cells of the adult testis, rarely turn
      over. However, their elimination with ethane dimethanesulfonate (EDS) is followed
      by the appearance of new, fully functional adult Leydig cells. The cells that
      give rise to the new Leydig cells have not been well characterized, and little is
      known about the mechanism by which they are regulated. We isolated cells
      expressing platelet-derived growth factor receptor-alpha, but not 3beta
      hydroxysteroid dehydrogenase (3beta-HSD(neg)) from the testes of EDS-treated
      adult rats. Depending on conditions, these cells proliferated indefinitely or
      differentiated and produced testosterone. To localize these cells and to
      determine the effect of the testicular environment on their function, the
      seminiferous tubules and testicular interstitium were physically separated and
      cultured. During the first 72 h in culture, 3beta-HSD(neg) cells on the tubule
      surfaces underwent divisions. Some of these cells later expressed 3beta-HSD and
      produced testosterone. Removal of the newly formed 3beta-HSD(pos) cells from the
      tubule surfaces with EDS, followed by further culture of the stripped tubules,
      resulted in the reappearance of testosterone-producing cells. These results,
      taken together, suggest that the precursors for newly formed Leydig cells are
      stem cells, with many if not all situated on the surfaces of the seminiferous
      tubules. Although normally quiescent, the stem cells are capable of self-renewal
      and differentiation. The development of the tubule culture system should provide
      a valuable in vitro approach to assess the role(s) of niche components on the
      function of adult Leydig stem cells despite their residing in a complex mammalian
      tissue.

PMID- 22865374
TI  - On the efficiency of two-stage response-adaptive designs.
AB  - In this paper, we investigate the efficiency of response-adaptive locally optimum
      designs. We focus on two-stage adaptive designs, where after the first stage the
      accrued data are used to determine a locally optimum design for the second stage.
      On the basis of an explicit expansion of the information matrix, we compare the
      variance of the maximum likelihood estimates obtained from a two-stage adaptive
      design and a fixed design without adaptation. For several one-parameter models,
      we provide explicit expressions for the relative efficiency of these two designs,
      which is seen to depend sensitively on the statistical problem under
      investigation. In particular, we show that in non-linear regression models with
      moderate or large variances the first-stage sample size of an adaptive design
      should be chosen sufficiently large in order to address variability in the
      interim parameter estimates. These findings support the results of recent
      simulation studies conducted to compare adaptive designs in more complex
      situations. We finally present an application to a real clinical dose-finding
      trial aiming at the estimation of the smallest dose achieving a certain
      percentage of the maximum treatment effect by using a three-parameter Emax model.

PMID- 22865375
TI  - Reproductive toxicity and histopathological changes induced by lambda-cyhalothrin
      in male mice.
AB  - Lambda-cyhalothrin (LCT) is a widely used broad-spectrum pyrethroid insecticide.
      Oral LCT administration to adult male mice at 3 doses (0.2, 0.4, and 0.8
      mg/kg/day) for 6 weeks caused a significant reduction in the weight of the
      seminal vesicles. The epididymal sperm count was lower in mice that received at
      the highest dose than in control mice. However, the proportions of live and
      motile spermatozoa were reduced at both the medium and the high doses compared
      with control mice. All doses induced an increase in the number of morphologically
      abnormal spermatozoa. Histopathological observations of the testes, liver,
      kidneys, and spleen showed dose-related degenerative damage in LCT-treated mice.
      The results indicate that LCT has reproductive toxicity, hepatotoxicity,
      nephrotoxicity, and splenotoxicity in male mice at the tested doses. (c) 2012
      Wiley Periodicals, Inc. Environ Toxicol 29: 750-762, 2014. 

PMID- 22865376
TI  - Opisthotonic posturing in an adult with a cerebellopontine angle mass.

PMID- 22865377
TI  - Relapsing polychondritis revealed by basal ganglia lesions.

PMID- 22865378
TI  - Long-lasting effect of levodopa on holmes' tremor.

PMID- 22865379
TI  - Nocturnal Frontal Lobe Epilepsy vs Parasomnias.
AB  - OPINION STATEMENT: The diagnosis and treatment of nocturnal events can present
      significant challenges to the clinician. Correct diagnosis is the first step
      towards appropriate treatment, but may not be straightforward. In particular, non
      rapid eye movement (NREM) arousal parasomnias, such as sleepwalking, sleep
      terrors, and confusional arousal can present in a similar fashion to nocturnal
      frontal lobe epilepsy (NFLE); dramatic and often bizarre behaviors from sleep are
      features of both conditions, and may result in diagnostic confusion. A careful
      clinical history, however, often enables accurate diagnosis, and the frontal lobe
      epilepsy and parasomnia (FLEP) scale, a validated questionnaire for the diagnosis
      of nocturnal events, can add diagnostic confidence. Recording of events on video
      EEG-polysomnography is required if diagnostic doubt remains although is not
      always achievable, particularly if events are occurring infrequently. Treatments
      for NFLE and parasomnias are different, but lifestyle modification and treatment
      of coexisting sleep disorders (such as obstructive sleep apnoea) may have a role
      in both. In NFLE, medical treatment with antiepileptic drugs, particularly
      carbamazepine and topiramate, forms the mainstay of treatment; a small proportion
      of individuals with treatment-resistant seizures may benefit from epilepsy
      surgery. For parasomnias, reassurance and the removal of priming and
      precipitating factors is often sufficient. A minority of individuals will,
      however, need medical treatment, usually with benzodiazepines or tricyclic
      antidepressants. Unfortunately, there are few data on which to base treatment
      decisions in this area, with the evidence comprising predominantly case reports
      and case series. Well-designed studies, including randomised control trials, are
      needed and may require a multicentre approach.

PMID- 22865380
TI  - Blocking human enterovirus 71 replication by targeting viral 2A protease.
AB  - OBJECTIVES: Human enterovirus 71 (EV-71), a member of the Enterovirus genus,
      constitutes a major public health issue in the Asia-Pacific region, where it is
      associated with several severe neurological complications. There is currently no
      effective vaccine or antiviral against EV-71. The aim of this study was to
      determine whether the six amino acid peptide LVLQTM, which was previously shown
      to inhibit human rhinovirus (HRV) 2A protease (2A(pro)) activity in vitro and HRV
      replication in vivo in mice, could be of more general use against enteroviruses
      and more particularly against EV-71. METHODS: To investigate whether the LVLQTM
      peptide was a pseudosubstrate of EV-71 2A(pro), a recombinant luciferase
      containing the LVLQTM sequence was designed so that recognition of this sequence
      by 2A(pro) led to luciferase activation. Direct interaction between EV-71 2A(pro)
      and the LVLQTM peptide was further confirmed by isothermal titration calorimetry.
      We then tested the effects of the peptide on EV-71 2A(pro) cleavage activity and
      EV-71 replication in HeLa cells. RESULTS: We showed that the LVLQTM peptide
      behaved as an effective substrate analogue of EV-71 2A(pro), which binds into the
      active site of the protease with a dissociation rate constant of 9.6 MUM.
      Moreover, LVLQTM significantly inhibited eIF4G cleavage activity of 2A(pro) as
      well as EV-71 replication in HeLa cells. CONCLUSIONS: This study demonstrates
      that the LVLQTM peptide that has previously been shown to inhibit HRV replication
      is also an effective inhibitor of EV-71 2A(pro) and therefore of EV-71
      replication, opening new doors in the development of new antivirals against EV
      71.

PMID- 22865381
TI  - Epidemiology and genetic characteristics of extended-spectrum beta-lactamase
      producing Gram-negative bacteria causing urinary tract infections in long-term
      care facilities.
AB  - OBJECTIVES: To assess risk factors for acquiring extended-spectrum beta-lactamase
      producing Gram-negative bacteria (ESBL+ GN) causing urinary tract infections
      (UTIs) in long-term care facilities (LTCFs). METHODS: A prospective case-case
      control study was carried out. In the first study, cases were defined as patients
      harbouring ESBL+ GN, while, in the second study, cases were defined as patients
      harbouring ESBL-negative (ESBL-) GN. Controls were selected by simple random
      sampling from patients without GN infection. ESBL determinants were characterized
      by hybridization, and confirmed by PCR and sequencing. RESULTS: The study
      involved 297 LTCF patients (99 with ESBL+ GN UTI, 99 with ESBL- GN UTI and 99
      without GN infection). ESBL+ GN UTIs were due to Escherichia coli (64%), Proteus
      mirabilis (25%) and Klebsiella pneumoniae (11%). The CTX-M-type enzymes were the
      most prevalent (73% of isolates), whereas TEM- and SHV-type ESBLs and AmpC-type
      enzymes were less prevalent (10%, 2% and 15% of isolates, respectively). Patients
      with ESBL+ GN UTI were more likely to have a permanent urinary catheter (OR 15,
      95% CI 6.9-30.5) and to have received antimicrobial therapy in the previous 30
      days (OR 4, 95% CI 1.2-10.9). After adjusting for type, dosage and duration of
      antibiotic, exposure to >=7 days of quinolones and third-generation
      cephalosporins was associated with the highest risk of ESBL+ GN UTI development
      (OR 7, 95% CI 1.2-40). Independent risk factors for acquiring ESBL- GN UTIs were
      previous surgical procedures (OR 2, 95% CI 1.1-4) and the presence of a urinary
      catheter (OR 8, 95% CI 4-16). No specific antibiotics remained a significant risk
      for ESBL- GN UTI after adjusting for demographic and clinical risk factors.
      CONCLUSIONS: Exposure to >=7 days of quinolones and third-generation
      cephalosporins significantly increases the risk of ESBL+ GN UTI. Interventions
      aimed at improving compliance with antimicrobial stewardship principles should be
      further developed and implemented in LTCFs.

PMID- 22865382
TI  - Fidaxomicin: a new option for the treatment of Clostridium difficile infection.
AB  - The two drugs currently recommended for the treatment of Clostridium difficile
      infection (CDI), namely vancomycin and metronidazole, are both associated with
      high rates of recurrence of infection. Hence there is a need for new treatment
      options. The novel oral macrocyclic antibiotic fidaxomicin (previously known as
      PAR-101, OPT-80 and difimicin) was recently approved in the USA and in Europe for
      the treatment of CDI. Clinical trials have shown non-inferiority with regard to
      clinical cure when compared with oral vancomycin, and reduced rates of recurrence
      of infection, with a concomitant increase in the overall rate of sustained
      response, although improved sustained response was not seen in the sub-group of
      patients infected with the C. difficile NAP1/B1/027 strain. The introduction of
      fidaxomicin extends the options for the treatment of CDI and may help to reduce
      the burden of this disease if fewer patients have recurrence of infection.

PMID- 22865383
TI  - In vitro susceptibility and cellular uptake for a new class of antimicrobial
      agents: dinuclear ruthenium(II) complexes.
AB  - OBJECTIVES: To determine the in vitro susceptibility and cellular uptake for a
      series of dinuclear ruthenium(II) complexes [{Ru(phen)(2)}(2){MU-bb(n)}](4+)
      (Rubb(n)), and the mononuclear complexes [Ru(Me(4)phen)(3)](2+) and
      [Ru(phen)(2)(bb(7))](2+) against Staphylococcus aureus, methicillin-resistant S.
      aureus, Escherichia coli and Pseudomonas aeruginosa. METHODS: The in vitro
      susceptibility was determined by MIC and MBC assays, and time-kill curve
      experiments, while the cellular uptake was evaluated by monitoring the
      fluorescence of the complexes remaining in the supernatant of the cultures after
      incubation for various periods of time, flow cytometry and confocal microscopy.
      RESULTS: Rubb(12) and Rubb(16) are highly active, with MIC and MBC values of 1-2
      mg/L (0.5-1 MUM) for the two Gram-positive strains and 2-4 mg/L for E. coli and
      16-32 mg/L for P. aeruginosa. Rubb(16) showed equal or better activity (on a
      molar basis) to gentamicin and ampicillin for all strains apart from P.
      aeruginosa. The relative MBC to MIC values indicated that Rubb(12) and Rubb(16)
      are bactericidal, and from the time-kill curve experiments, the ruthenium
      complexes can kill the bacteria within 2-6 h. The cellular uptake studies
      demonstrated that the observed antimicrobial activity is correlated with the
      level of uptake of the ruthenium complexes. Confocal microscopy confirmed the
      cellular uptake of Rubb(16), and tentatively suggested that the ruthenium complex
      is localized in the bacteria. CONCLUSIONS: The inert dinuclear ruthenium(II)
      complexes Rubb(12) and Rubb(16) have potential as new antimicrobial agents. The
      structure of the dinuclear ruthenium complexes can be readily further modified in
      order to increase their selectivity for bacteria over human cells.

PMID- 22865384
TI  - Erythrocyte-derived sphingosine-1-phosphate stabilizes basal hydraulic
      conductivity and solute permeability in rat microvessels.
AB  - Exogenous sphingosine-1-phosphate (S1P), a lipid mediator in blood, attenuates
      acute microvascular permeability increases via receptor S1P1 to stabilize the
      endothelium. To evaluate the contribution of erythrocytes as an endogenous source
      of S1P to the regulation of basal permeability, we measured permeability
      coefficients in intact individually perfused venular microvessels of rat
      mesentery. This strategy also enabled the contributions of other endogenous S1P
      sources to be evaluated. Apparent permeability coefficients (P(S)) to albumin and
      alpha-lactalbumin and the hydraulic conductivity of mesenteric microvessels were
      measured in the presence or absence of rat erythrocytes or rat erythrocyte
      conditioned perfusate. Rat erythrocytes added to the perfusate were the principal
      source of S1P in these microvessels. Basal P(S) to albumin was stable and typical
      of blood-perfused microvessels (mean 0.5 * 10(-6) cm/s) when erythrocytes or
      erythrocyte-conditioned perfusates were present. When they were absent, P(S) to
      albumin or alpha-lactalbumin increased up to 40-fold (over 10 min). When
      exogenous S1P was added to perfusates, permeability returned to levels comparable
      with those seen in the presence of erythrocytes. Addition of SEW 2871, an agonist
      specific for S1P1, in the absence of red blood cells reduced P(S)(BSA) (40-fold
      reduction) toward basal. The specific S1P1 receptor antagonist (W-146) reversed
      the stabilizing action of erythrocytes and increased permeability (27-fold
      increase) in a manner similar to that seen in the absence of erythrocytes.
      Erythrocytes are a primary source of S1P that maintains normal venular
      microvessel permeability. Absence of erythrocytes or conditioned perfusate in in
      vivo and in vitro models of endothelial barriers elevates basal permeability.

PMID- 22865385
TI  - Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of
      contractile activation independently of strong crossbridges.
AB  - Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere
      length (SL) in cardiac muscle and is considered to be the cellular basis of the
      Frank-Starling law of the heart. SL dependence may involve changes in myofilament
      lattice spacing and/or myosin crossbridge orientation to increase probability of
      binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC)
      variant, which has enhanced Ca(2+) binding affinity, to test the hypotheses that
      the intrinsic properties of cTnC are important in determining 1) thin filament
      binding site availability and responsiveness to crossbridge activation and 2) SL
      dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost
      SL dependence of the Ca(2+) sensitivity of force. This occurred despite
      maintaining the typical SL-dependent changes in maximal force (F(max)). Osmotic
      compression of preparations at SL 2.0 MUm with 3% dextran increased F(max) but
      not pCa(50) in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC
      cTn exchanged trabeculae exhibited increases in both F(max) and pCa(50).
      Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 MUm
      decreased F(max) and pCa(50) in WT cTnC-cTn trabeculae to levels measured at SL
      2.0 MUm, whereas only F(max) was decreased with L48Q cTnC-cTn. Overall, these
      results suggest that L48Q cTnC confers reduced crossbridge dependence of thin
      filament activation in cardiac muscle and that changes in the Ca(2+) sensitivity
      of force in response to changes in SL are at least partially dependent on
      properties of thin filament troponin.

PMID- 22865386
TI  - Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a
      positive feedback loop involving Rho kinase and PKCbeta2.
AB  - We previously reported that acute inhibition of the RhoA/Rho kinase (ROCK)
      pathway normalized contractile function of diabetic rat hearts, but the
      underlying mechanism is unclear. Protein kinase C (PKC) beta(2) has been proposed
      to play a major role in diabetic cardiomyopathy at least in part by increasing
      oxidative stress. Further evidence suggests that PKC positively regulates RhoA
      expression through induction of inducible nitric oxide synthase (iNOS) in
      diabetes. However, in preliminary studies, we found that inhibition of ROCK
      itself reduced RhoA expression in diabetic hearts. We hypothesized that there is
      an interaction between RhoA/ROCK and PKCbeta(2) in the form of a positive
      feedback loop that sustains their activation and the production of reactive
      oxygen species (ROS). This was investigated in cardiomyocytes isolated from
      diabetic and control rat hearts, incubated with or without cytochalasin D or
      inhibitors of ROCK, RhoA, PKCbeta(2), or iNOS. Inhibition of RhoA and ROCK
      markedly attenuated the diabetes-induced increases in PKCbeta(2) activity and
      iNOS and RhoA expression in diabetic cardiomyocytes, while having no effect in
      control cells. Inhibition of PKCbeta(2) and iNOS also normalized RhoA expression
      and ROCK overactivation, whereas iNOS inhibition reversed the increase in
      PKCbeta(2) activity. Each of these treatments also normalized the diabetes
      induced increase in production of ROS. Actin cytoskeleton disruption attenuated
      the increased expression and/or activity of all of these targets in diabetic
      cardiomyocytes. These data suggest that, in the diabetic heart, the RhoA/ROCK
      pathway contributes to contractile dysfunction at least in part by sustaining
      PKCbeta(2) activation and ROS production via a positive feedback loop that
      requires an intact cytoskeleton.

PMID- 22865387
TI  - Gene deletion of P2Y4 receptor lowers exercise capacity and reduces myocardial
      hypertrophy with swimming exercise.
AB  - Nucleotides released within the heart under pathological conditions can be
      involved in cardioprotection or cardiac fibrosis through the activation
      purinergic P2Y(2) and P2Y(6) receptors, respectively. We previously demonstrated
      that adult P2Y(4)-null mice display a microcardia phenotype related to a cardiac
      angiogenic defect. To evaluate the functional consequences of this defect, we
      performed here a combination of cardiac monitoring and exercise tests. We
      investigated the exercise capacity of P2Y(4) wild-type and P2Y(4)-null mice in
      forced swimming and running tests. Analysis of their stress, locomotion, and
      resignation was realized in open field, black and white box, and tail suspension
      experiments. Exercise-induced cardiac hypertrophy was evaluated after repeated
      and prolonged exercise in P2Y(4) wild-type and P2Y(4)-null hearts. We showed that
      P2Y(4)-null mice have a lower exercise capacity in both swimming and treadmill
      tests. This was not related to decreased motivation or increased stress, since
      open field, white and black box, and mouse tail suspension tests gave comparable
      results in P2Y(4) wild-type and P2Y(4)-null mice. Heart rate and blood pressure
      rose normally in P2Y(4)-null swimming mice equipped with a telemetric implant. On
      the contrary, we observed a delayed recovery of postexercise blood pressure after
      exercise in P2Y(4)-null mice. The heart rate increment in response to
      catecholamines was also similar in P2Y(4) wild-type and P2Y(4)-null implanted
      mice, which is consistent with a similar level of cardiac beta-receptor
      expression. Interestingly, the heart of P2Y(4)-null mice displayed a reduced
      sympathetic innervation associated with a decreased norepinephrine level. We also
      demonstrated that exercise-induced cardiac hypertrophy was lower in P2Y(4)-null
      mice after repeated and prolonged exercise. This was associated with a lower
      increase in cardiomyocyte size and microvessel density. In conclusion, besides
      its role in cardiac development, P2Y(4) receptor could constitute an important
      regulator of acute and chronic response to exercise.

PMID- 22865389
TI  - Independent and interactive effects of preload and afterload on the pump function
      of the isolated lymphangion.
AB  - We tested the responses of single, isolated lymphangions to selective changes in
      preload and the effects of changing preload on the response to an imposed
      afterload. The methods used were similar to those described in our companion
      paper. Step-wise increases in input pressure (P(in); preload) over a pressure
      range between 0.5 and 3 cmH(2)O, at constant output pressure (P(out)), led to
      increases in end-diastolic diameter, decreases in end-systolic diameter, and
      increases in stroke volume. From a baseline of 1 cmH(2)O, P(in) elevation by 2-7
      cmH(2)O consistently produced an immediate fall in stroke volume that
      subsequently recovered over a time course of 2-3 min. Surprisingly, this
      adaptation was associated with an increase in the slope of the end-systolic
      pressure-volume relationship, indicative of an increase in contractility.
      Lymphangions subjected to P(out) levels exceeding their initial ejection limit
      would often accommodate by increasing diastolic filling to strengthen contraction
      sufficiently to match P(out). The lymphangion adaptation to various pressure
      combinations (P(in) ramps with low or high levels of P(out), P(out) ramps at low
      or intermediate levels of P(in), and combined P(in) + P(out) ramps) were analyzed
      using pressure-volume data to calculate stroke work. Under relatively low imposed
      loads, stroke work was maximal at low preloads (P(in) ~2 cmH(2)O), whereas at
      more elevated afterloads, the optimal preload for maximal work displayed a broad
      plateau over a P(in) range of 5-11 cmH(2)O. These results provide new insights
      into the normal operation of the lymphatic pump, its comparison with the cardiac
      pump, and its potential capacity to adapt to increased loads during edemagenic
      and/or gravitational stress.

PMID- 22865388
TI  - Pharmacological inhibition of soluble epoxide hydrolase provides cardioprotection
      in hyperglycemic rats.
AB  - Glycemic regulation improves myocardial function in diabetic patients, but
      finding optimal therapeutic strategies remains challenging. Recent data have
      shown that pharmacological inhibition of soluble epoxide hydrolase (sEH), an
      enzyme that decreases the endogenous levels of protective epoxyeicosatrienoic
      acids (EETs), improves glucose homeostasis in insulin-resistant mice. Here, we
      tested whether the administration of sEH inhibitors preserves cardiac myocyte
      structure and function in hyperglycemic rats. University of California-Davis-type
      2 diabetes mellitus (UCD-T2DM) rats with nonfasting blood glucose levels in the
      range of 150-200 mg/dl were treated with the sEH inhibitor 1-(1-acetypiperidin-4
      yl)-3-adamantanylurea (APAU) for 6 wk. Administration of APAU attenuated the
      progressive increase of blood glucose concentration and preserved mitochondrial
      structure and myofibril morphology in cardiac myocytes, as revealed by electron
      microscopy imaging. Fluorescence microscopy with Ca(2+) indicators also showed a
      40% improvement of cardiac Ca(2+) transients in treated rats. Sarcoplasmic
      reticulum Ca(2+) content was decreased in both treated and untreated rats
      compared with control rats. However, treatment limited this reduction by 30%,
      suggesting that APAU may protect the intracellular Ca(2+) effector system. Using
      Western blot analysis on cardiac myocyte lysates, we found less downregulation of
      sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the main route of Ca(2+)
      reuptake in the sarcoplasmic reticulum, and lower expression of hypertrophic
      markers in treated versus untreated UCD-T2DM rats. In conclusion, APAU enhances
      the therapeutic effects of EETs, resulting in slower progression of
      hyperglycemia, efficient protection of myocyte structure, and reduced Ca(2+)
      dysregulation and SERCA remodeling in hyperglycemic rats. The results suggest
      that sEH/EETs may be an effective therapeutic target for cardioprotection in
      insulin resistance and diabetes.

PMID- 22865390
TI  - Early parenting program as intervention strategy for emotional distress in first
      time mothers: a propensity score analysis.
AB  - The purpose of this study is to evaluate the effectiveness of a single session
      intervention designed to reduce emotional distress in first-time mothers. We held
      a parenting class for first-time mothers who had given birth at a university
      hospital in Tokyo, Japan. The program of the class consists of lectures on infant
      care and group discussion, which is a common form of intervention in Japan. The
      effectiveness of intervention is assessed according to differences in emotional
      distress experienced by class participants and nonparticipants, and analyzed by
      the use of a propensity score method to avoid self-selection bias. In order to be
      more confident about our results, we employ several variations of this method.
      Results from statistical analysis show that although the effectiveness of the
      intervention was limited, it was able to alleviate subjects' loss of self
      confidence as mothers. Because this outcome shows a good degree of consistency
      across methods, it can be considered robust. Moreover, it is roughly consistent
      with previous studies. Effectiveness can probably be increased by developing a
      program that improves upon the intervention. 

PMID- 22865391
TI  - Engineered bone tissue associated with vascularization utilizing a rotating wall
      vessel bioreactor.
AB  - Tissue-engineered bone has attracted much attention as an alternative material
      for bone grafting; however, implantable bone tissue of an appropriate size and
      shape for clinical use has not yet been developed due to a lack of
      vascularization, which results in necrosis of the seeded cells in vivo. This is
      the first report of bone tissue engineering associated with vascularization by co
      culturing bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial
      cells (ECs) within a porous scaffold using a rotating wall vessel (RWV)
      bioreactor. MSC-derived ECs were identified by immunofluorescence staining for
      von Willebrand factor (vWF) and by flow cytometry for CD31 expression. The tissue
      obtained was histochemically analyzed using toluidin blue, hematoxylin and eosin,
      anti-osteopontin antibody, anti-osteocalcin antibody, and tomato-lectin stain.
      Results showed that bone tissue containing vascular-like structures was
      generated. Three-dimensional culture condition created by medium flow in the RWV
      vessel and the interaction of MSCs with MSC-derived ECs might provide the cells
      an advantage in the construction of three-dimensional bone tissue with blood
      vessels.

PMID- 22865392
TI  - Community-acquired left-sided Pseudomonas aeruginosa endocarditis in a patient
      without intravenous drug use.
AB  - We present a case of community-acquired left-sided Pseudomonas aeruginosa
      endocarditis in a person without intravenous drug use. The patient presented with
      facial numbness and did not have any predisposing condition for endocarditis. He
      was treated successfully with valvular surgery, along with combination
      antibiotics.

PMID- 22865393
TI  - National MRSA rates run along with fair play of national football teams: a cross
      national data analysis of the European Football Championship, 2008.
AB  - BACKGROUND: We aimed to assess the relationship between national methicillin
      resistant Staphylococcus aureus (MRSA) proportions and indicators for fair play
      in the European Football Championship, 2008. FINDING: We obtained methicillin
      resistance data for S. aureus from the European Antimicrobial Resistance
      Surveillance System (EARSS) project. All teams which qualified for the final
      tournament and had reported data to the EARSS were included in the analysis.
      Hosting countries were excluded. The number of yellow and red cards was
      calculated per 100 min as an indicator for fair play. Red cards were weighted
      like yellow cards. We calculated correlations between antibiotic resistance and
      use using two-tailed Spearman's coefficient (r) for non-parametric correlations.
      In 2008, 16 countries qualified for the European Football Championship. Five
      countries (Turkey, Switzerland, Croatia, Russia and Austria) did not report MRSA
      data to the EARSS and/or were hosting countries. The correlation of national MRSA
      proportions and the fair play indicator was highly significant (p = 0.038), with
      a correlation coefficient of 0.632. CONCLUSION: This study shows that national
      MRSA proportions increase with more unfair play of the national teams: Sweden and
      the Netherlands played the fairest and had the lowest MRSA proportions. However,
      it remains to be proven (e.g. in the European Football Championship, 2012)
      whether this fair play indicator, indeed, can serve as an indicator for adherence
      with MRSA guidelines or whether this correlation cannot be substantiated.

PMID- 22865394
TI  - Influence of archaeological environment factors in alteration processes of copper
      alloy artifacts.
AB  - The article presents the experimental results obtained by combining noninvasive
      techniques (OM, SEM/EDX, XRF) to analyze three artifacts made of copper alloys
      discovered in a inhumation tomb (2) and in the soil profile (1) in archaeological
      sites from Neamt County Romania. To uncover the mechanism of alteration thereof
      during their longtime underground stay in specific chemical conditions and under
      the influence of other pedological factors, the corrosion products must be
      identified. The excess of the chloride ion, from burial site, disturbs the
      Liesegang effect, transforming the bulk in a stratified sponge structure with
      chlorapatite and hydroxyapatite. Some of the compounds from primary and secondary
      patina can be found on the surface of the bulk, as color stains. The presence of
      alloy components (Cu, Sn, Pb, Zn, Fe, etc.) and of the underground contamination
      components, allowed us to establish the origin of the ore, the manufacture
      technology and we identified other materials which affected the artifacts after
      abandonment.

PMID- 22865395
TI  - Effects of increased overnight supervision on resident education, decision
      making, and autonomy.
AB  - BACKGROUND: New supervisory regulations highlight the challenge of balancing
      housestaff supervision and autonomy. To better understand the impact of increased
      supervision on residency training, we investigated housestaff perceptions of
      education, autonomy, and clinical decision-making before and after implementation
      of an in-hospital, overnight attending physician (nocturnist). METHODS: We
      established a nocturnist program in July 2010 at our academic, tertiary care
      medical center. We administered pre-surveys and post-surveys of internal medicine
      residents on night float rotation during the 2010-2011 academic year. We surveyed
      residents before and after experiencing the nocturnist program. RESULTS:
      Housestaff reported an increase in the clinical value of the night float rotation
      (3.95 vs 4.27, P = 0.01) and the adequacy of overnight supervision (3.65 vs 4.30,
      P < 0.0001) without a change in decision-making autonomy (4.35 vs 4.45, P =
      0.44). Trainees agreed that nocturnist supervision positively impacted patient
      outcomes (3.79 vs 4.30, P = 0.002). Housestaff contacted attendings more
      frequently for transfers from outside facilities (2.00 vs 3.20, P = 0.006),
      during adverse events (2.51 vs 3.25, P = 0.04), prior to ordering invasive
      diagnostics (1.75 vs 2.76, P = 0.004), and prior to vasopressor use (1.52 vs
      2.40, P = 0.004). Residents' fear of revealing knowledge gaps and desire to make
      decisions independently did not change. CONCLUSIONS: Increased overnight
      supervision enhanced the clinical value of the night float rotation, increased
      rates of attending contact during critical clinical decision-making, and improved
      perception of patient care. These changes occurred without a decrease in
      housestaff's perceived decision-making autonomy.

PMID- 22865396
TI  - The impact of simple orchiectomy on semen quality and endocrine parameters in
      postpubertal cryptorchid men.
AB  - PURPOSE: The main objectives of this retrospective cohort study were to evaluate
      reproductive endocrine and semen profiles before and after simple orchiectomy in
      patients with unilateral postpubertal cryptorchidism and to investigate the
      relationship between hormone levels and histopathology of the removed testis.
      METHODS: We evaluated 40 adult males who were admitted to our clinic, between
      2001 and 2007, with unilateral undescended testis. Right orchiectomy was
      performed in 27 patients and left orchiectomy in 13. Semen analysis, serum
      inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      testosterone levels were examined in before and 3 months after orchiectomy.
      Orchiectomy materials were evaluated histopathologically. RESULTS: Semen
      parameters, as well as testosterone and LH levels, did not change in any
      histopathological subgroups in the postoperative follow-up. In patients with
      maturation arrest, mean serum inhibin B level statistically significantly
      decreased from 160.9 to 83.5 pg/ml, and mean FSH level significantly increased
      from 4.8 to 7.6 mIU/ml after orchiectomy (p value, 0.008 and 0.008,
      respectively). Though, the levels were still within the normal range of the two
      hormones. CONCLUSIONS: Simple orchiectomy does not have any effect on semen
      parameters and testosterone level in patients with postpubertal cryptorchidism.
      The change in inhibin B and FSH levels after orchiectomy in patients with
      maturation arrest is not clinically significant.

PMID- 22865397
TI  - Multi-method comparison of carrot quality from a conventional and three organic
      cropping systems with increasing levels of nutrient recycling.
AB  - BACKGROUND: There is a need to advance the study of the effects of organic and
      conventional systems on product quality. In particular, little is known about the
      importance of different farming practices concerning nutrient cycling and the use
      of external inputs within organic farming for the quality characteristics of the
      products. In this study the quality characteristics of carrot grown under
      different farming practices (conventional and three organic cropping systems)
      over a two-year period were analysed with the aim of discriminating between
      organic and conventional and investigating the effect of different organic
      farming practices concerning nutrient recycling and use of external nutrient
      input. RESULTS: All quality characteristics measured did not give a clear
      differentiation between the carrots from the different growing systems, even when
      multivariate statistical evaluation (principal component analysis) was applied,
      because of the significance of the differences between the field replicates
      within each management system and of the seasonality. Only some tendencies were
      emphasised over the two years that could be related to the fertilisation
      practices and the external inputs used. CONCLUSION: The results indicated that it
      was not possible to discriminate over the years between carrots from conventional
      and different organic cropping systems even though controlled conditions and a
      multi-method approach of analysis were adopted.

PMID- 22865398
TI  - Electronic fluxes during Diels-Alder reactions involving 1,2-benzoquinones:
      mechanistic insights from the analysis of electron localization function and
      catastrophe theory.
AB  - By means of the joint use of electron localization function (ELF) and Thom's
      catastrophe theory, a theoretical analysis of the energy profile for the hetero
      Diels-Alder reaction of 4-methoxy-1,2-benzoquinone 1 and methoxyethylene 2 has
      been carried out. The 12 different structural stability domains obtained by the
      bonding evolution theory have been identified as well as the bifurcation
      catastrophes (fold and cusp) responsible for the changes in the topology of the
      system. This analysis permits finding a relationship between the ELF topology and
      the evolution of the bond breaking/forming processes and electron pair
      rearrangements through the reaction progress in terms of the different ways of
      pairing up the electrons. The reaction mechanism corresponds to an asynchronous
      electronic flux; first, the O1-C5 bond is formed by the nucleophilic attack of
      the C5 carbon of the electron rich ethylene 2 on the most electrophilically
      activated carbonyl O1 oxygen of 1, and once the sigma bond has been completed,
      the formation process of the second O4?C6 bond takes place. In addition, the
      values of the local electrophilicity and local nucleophilcity indices in the
      framework of conceptual density functional theory accounts for the asychronicity
      of the process as well as for the observed regioselectivity.

PMID- 22865400
TI  - Intraoperative assessment of medial rectus pulley location in strabismus.
AB  - Purpose. Extraocular muscle (EOM) pulleys are important in eye movement
      physiology and may play a role in the outcome of strabismus surgery. Few studies
      have evaluated "normal" position of EOM pulleys. We sought to assess
      intraoperatively medial rectus (MR) pulley location and variations in a
      prospective observational case series. Methods. A total of 194 consecutive
      patients with all types of strabismus aged 2 to 64 years had primary surgery on
      MR. We conducted 357 measures of the distance between scleral insertion of MR and
      anterior part of the pulley. We compared results to preoperative angle of
      deviation, age, refraction, and position of eyes under anesthesia. Results.
      Median location of the anterior part of the MR's pulley is 12.03 mm from scleral
      insertion, varying from 8 to 15 mm. There is a strong relation with refraction
      (p=0.005) and with preoperative angle of deviation (p=0.00002) and deviation
      under anesthesia (p=0.0001). The MR's pulley tends to be more anterior in
      hyperopic cases and esotropias, and posterior in myopias and exotropias.
      Conclusions. Our study shows physiologic variations of MR's pulley position with
      evidence of an adaptation to biometric parameters of the globe, represented by
      refraction state of the eyes in our study. Elsewhere, strabismus leads to an
      independent variation of MR's pulley location evaluated relatively to muscle's
      scleral insertion, but probably not if evaluated relatively to the orbit. We
      discuss consequences on ocular motility and surgery of these variations. They may
      explain some unexpected effects of strabismus surgery. Further studies are needed
      to ascertain their real impact.

PMID- 22865399
TI  - Serum miR-18a: a potential marker for hepatitis B virus-related hepatocellular
      carcinoma screening.
AB  - BACKGROUND: Alpha-fetoprotein detection is currently mainly used in clinic for
      diagnosis of primary hepatocellular carcinoma (HCC). However, its sensitivity and
      specificity are not satisfying. Approximately 60-80 % of patients with HCC have
      an established background of chronic infection with hepatitis B virus (HBV).
      AIMS: To investigate the potential of serum microRNAs (miRNAs) as biomarkers for
      HBV-related HCC. METHODS: This study was divided into two phases: firstly, marker
      (miR-95, miR-18a, miR-10b, miR125a, and miR-378) detection by real-time
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sera
      from HBV patients with HCC (n = 15) and health subject (n = 15); and, secondly,
      marker validation by real-time qRT-PCR on HBV patients with HCC (n = 86) or
      hepatitis or cirrhosis (n = 30), and healthy subject (n = 45). RESULTS: Serum miR
      18a was significantly higher in HBV patients with HCC than healthy controls (p <
      0.01); serum miR-378 was significantly lower in HBV patients with HCC compared to
      healthy control (p < 0.05). Receiver operating characteristic (ROC) curve
      analyses suggested that serum miR-18a had significant diagnostic value for HBV
      related HCC. MiR-18a yielded an area under the curve (AUC) of ROC of 0.881 with
      86.1 % sensitivity and 75.0 % specificity in discriminating HBV-related HCC from
      healthy controls, and an AUC of ROC of 0.775 with 77.2 % sensitivity and 70.0 %
      specificity in discriminating HBV-related HCC from chronic hepatitis or
      cirrhosis. CONCLUSIONS: Our results suggest that serum miR-18a might serve as a
      novel and potential noninvasive biomarker for HBV-related HCC screening.

PMID- 22865401
TI  - Corneal biomechanical properties and anterior segment parameters in forme fruste
      keratoconus.
AB  - PURPOSE: To evaluate the sensitivity and specificity of corneal biomechanical
      metrics, anterior segment data, and a combination model in differentiating forme
      fruste keratoconus (FFK) from normal corneas. METHODS: A total of 50 FFK eyes
      were identified by calculation of the KISA index and recruited FFK group. Results
      were compared with 50 normal eyes (NG group) randomly selected from 50 patients.
      The following parameters were evaluated for their diagnostic capacity by
      evaluation of their receiver operating characteristic curves (ROC): corneal
      hysteresis (CH), corneal resistance factor (CRF), corneal astigmatism (Cyl),
      anterior chamber depth (ACD), corneal volume (CV) at 3 mm (CV3) and at 5 mm
      (CV5), maximum posterior elevation value (PEL), central corneal thickness (CCT),
      thinnest corneal thickness (TCT) and its coordinates (TCTx, TCTy ), the ratio
      TCT/CCT, pachymetric progression indexes (PPImin, PPIavg, and PPImax), and
      Ambrosio's relational thickness (ARTmin, ARTavg, and ARTmax). Logistic regression
      was attempted for identification of a combined diagnostic model. RESULTS:
      Significant differences were detected in all studied parameters except the Cyl,
      ACD, TCTx, and CV. Among individual parameters, the highest predictive accuracy
      was for ARTavg (area under the curve [AUC] 95.4%, sensitivity 90%, specificity
      88.9%) and TCT (AUC 95.3%, sensitivity 90.9%, specificity 89%). Sufficient
      predictive accuracy (AUC 99.4%, sensitivity 98.8%, specificity 94.6%) was
      identified in a diagnostic model that combined the CRF, ARTavg, and PEL
      parameters. CONCLUSIONS: None of the individual parameters provide sufficient
      diagnostic capacity in FFK. However, diagnostic models that combine biomechanical
      and tomographic data seem to provide high accuracy in differentiating FFK from
      normal corneas.

PMID- 22865402
TI  - A new strategy for diurnal intraocular pressure curve.
AB  - PURPOSE: To investigate whether there is agreement between intraocular pressure
      (IOP) readings in the supine position at 6 am upon awaking (before getting out of
      bed) and the IOP at 8 am, also measured in supine position after remaining 30
      minutes in this position. METHODS: In a sample of 50 eyes of 50 patients (normal,
      glaucoma suspect, and glaucoma patients), 6 am IOP was measured in the supine
      position upon awaking and before getting up, while 8 am IOP was measured on the
      same day, also in the supine position after 30 minutes in this position. RESULTS:
      The IOP values at 6 am were mean 16.06+/-3 mmHg; median 15.5 mmHg (range 10-25.5
      mmHg). For the 8 am readings, the average was 15.94+/-4 mmHg and the median 15
      mmHg (range 10-25.5 mmHg). The difference between mean 6 and 8 am IOPs was 0.13+/
      0.9 mmHg (confidence interval -0.14 to 0.40). Pearson correlation coefficient
      between the 6 and 8 am IOPs for the total sample was r=0.97 (p<0.05). There were
      no significant differences in behavior regarding eyes with high IOP as compared
      to normal IOP eyes (repeated-measure analysis of variance, p=0.72). CONCLUSIONS:
      The 8 am IOP readings obtained in the supine position and under the conditions
      described were equivalent to 6 am IOP readings (as the first measure of the
      diurnal pressure curve [DPC]). This new strategy for DPC will make it a widely
      used tool in daily practice since it spares the need for hospitalization or home
      measurements.

PMID- 22865403
TI  - Effect of phacoemulsification on drainage angle status in angle closure eyes with
      or without extensive peripheral anterior synechiae.
AB  - Purpose. To evaluate the anatomic effects of phacoemulsification on drainage
      angle status in primary angle closure glaucoma (PACG) using anterior segment
      optical coherence tomography (AS-OCT). Methods. A total of 62 eyes of 58 patients
      underwent cataract surgery in Farabi Rye Hospital, Tehran, Iran. 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 were angle and anterior segment parameters by AS-OCT and amount of
      peripheral anterior synechiae (PAS) by gonioscopy. Thirty-five eyes had PAS =180
      degrees (group 1) and 27 eyes had >180-degree synechial closure (group 2).
      Results. Mean age of the patients was 64.3+/-9.0 years. The mean extent of PAS
      was significantly reduced from 45.9 to 32.2 degrees (p<0.03) in group 1, and from
      277.4 to 159.0 degrees (p<0.001) in group 2. Group 2 showed significantly greater
      reduction in PAS extent (p<0.001). Angle opening distance and trabecular-iris
      space area at 500 um from the scleral spur measured by AS-OCT increased
      significantly in both groups (p<0.001 for both). Anterior chamber depth (ACD)
      increased and lens vault (LV) decreased after both procedures. However, the
      amount of change in ACD and LV and angle parameters were not significant between
      the 2 groups. Conclusions. Phacoemulsification resulted in opening of the
      drainage angle, deepening of the anterior chamber, and reduction of PAS extent in
      PACG eyes with or without extensive PAS. Greater reduction of PAS could be
      considered in eyes with PAS >180 degrees.

PMID- 22865405
TI  - Optical and visual quality comparison of implantable Collamer lens and laser in
      situ keratomileusis for myopia using an adaptive optics visual simulator.
AB  - Purpose. To compare optical and visual quality of the implantable Collamer lens
      (ICL) and laser in situ keratomileusis (LASIK) for myopia. Methods. An adaptive
      optics visual simulator (CRX1, Imagine Eyes, France) was used to simulate the
      vision after ICL implantation and LASIK procedure from the wavefront aberration
      pattern for -3 and -6 D. Monocular visual acuity (VA) at different contrasts and
      contrast sensitivity (CS) at 10, 20, and 25 cycles/degree (cpd) were measured for
      3- and 5-mm pupils. Modulation transfer function (MTF) and point spread function
      (PSF) were calculated for a 5-mm pupil. Results. The ICL showed a MTF near of
      diffraction-limited MTF, but the post-LASIK of MTF worsened moving away from both
      curves. Statistically significant differences were found in VA between both
      procedures for all conditions (p<0.05). For -3 D ICL and LASIK, we did not find
      statistically significant differences in CS between the procedures for both
      pupils and any spatial frequencies (p>0.05). But for -6 D ICL and LASIK, the
      effect of aberrations became apparent, finding statistically significant
      differences in CS between both procedures for 2 pupils and all spatial
      frequencies evaluated (p<0.05). In all cases optical and visual quality was
      better with the ICL procedure. Conclusions. Both ICL and LASIK procedures provide
      good optical and visual quality, although the ICL provides better outcomes,
      especially for large refractive errors and pupil sizes. These outcomes are due to
      the LASIK procedure inducing higher higher-order aberrations than ICL
      implantation.

PMID- 22865404
TI  - Choroid thickness measurement with RTVue optical coherence tomography in
      emmetropic eyes, mildly myopic eyes, and highly myopic eyes.
AB  - PURPOSE: To evaluate choroid thickness (CT) with RTVue spectral domain optical
      coherence tomography (SD-OCT) and the effect of age and myopia in eyes without
      posterior complications.? METHODS: In this multicenter cross-sectional study, all
      enrolled patients were over age 18 and divided them in 3 groups based on
      refraction: emmetropia (+1 D to -1 D), mild myopia (-1 D to -6 D), and high
      myopia (-6 D to -20 D) groups. Horizontal scans through the fovea were acquired
      with RTVue OCT (Optovue Inc., Fremont, California, USA). Choroid thickness was
      measured at 500 um intervals up to 1,500 um temporal and nasal to the fovea by 2
      graders. Mean CT was calculated based on the average of the 7 locations.
      Statistical analysis was performed to evaluate CT at each location, the effects
      of age and myopia, and grader agreement. ? RESULTS: A total 85 eyes of 85
      subjects (30 emmetropic, 24 myopic, and 31 high myopic) were enrolled. Excellent
      grader agreement was observed with an intraclass correlation coefficient (ICC)
      >0.97. The mean CT was 248.2+/-78.5 (um) for emmetropia (age = 58+/-18), 247.0+/
      85.4 (um) for myopia (age = 45+/-20), and 131.5+/-70.9 (um) for high myopia (age
      = 54+/-13). The mean CT was not significantly different between emmetropia and
      myopia groups, which were significantly thicker than high myopia group. The
      overall slope of age-related change for the mean CT was -1.95 um/y and the effect
      of age differed among the groups. CONCLUSIONS: Choroid thickness can be measured
      from RTVue OCT images with good reproducibility. Age and high myopia appear to
      negatively affect CT. The age effect may vary with refraction groups.

PMID- 22865406
TI  - Impact of Ga-68 DOTATOC PET/CT on the diagnosis and treatment of patients with
      multiple endocrine neoplasia.
AB  - PURPOSE: To evaluate the impact of Ga-68 DOTATOC PET/CT on diagnosis and
      therapeutic management of patients with multiple endocrine neoplasia (MEN).
      MATERIALS AND METHODS: We did 28 Ga-68 DOTATOC PET/CT in 21 MEN patients (10
      female, 11 men; mean age 41.3 years). 109 lesions detected were classified into
      MEN-associated lesions [i.e., neuroendocrine tumors (NET)] and non-MEN-associated
      lesions for PET, CT, and PET/CT. The impact of Ga-68 DOTATOC PET/CT on diagnosis
      and therapeutic management of patients with MEN were assessed by the records of
      the interdisciplinary NET tumor board including histopathological findings,
      clinical and radiological follow-up. RESULTS: Ga-68 DOTATOC PET/CT had an impact
      on diagnosis and therapeutic management in 10/21 (47.6%) MEN patients. For
      detecting NET lesions in MEN patients Ga-68 DOTATOC PET/CT reached a
      sensitivity/specificity of 91.7%/93.5%. There was a significant difference for
      the detection rate between Ga-68 DOTATOC PET/CT and CT alone (p < 0.001) both
      using contrast-agent (p = 0.002) or not (p < 0.001) and also a significant
      difference between contrast-enhanced (CE-) CT and non-CE-CT alone (p = 0.006).
      CONCLUSIONS: GA-68 DOTATOC PET/CT allows a high detection rate of NET lesions in
      the context of MEN-1 syndrome as well as influence therapeutic management in
      nearly up to half of the patients. GA-68 DOTATOC PET/CT should include a CE-CT to
      improve MEN-associated NET lesion detection.

PMID- 22865407
TI  - Discrepancy of left and right hip bone mineral density (BMD) in Thai women:
      diagnostic agreement and misclassification.
AB  - OBJECTIVE: To determine the diagnostic agreement and the degree of
      misclassification when using data from the left and right hips. METHODS: The
      cross-sectional study of 1,943 perimenopausal and postmenopausal Thai women, who
      had bone mineral density (BMD) measurements at the left (non-dominant) and right
      hips for the screening of low bone mass (LBM) or osteoporosis (OP) in the
      Department of Radiology, Faculty of Medicine, Chiang Mai University from
      September 2008 to August 2010 was performed. The kappa statistic was used to
      assess diagnostic agreement. The prevalence of LBM and OP and the percentage of
      misclassification were reported. RESULTS: There was a significant correlation
      between the left and right BMD values for the femoral neck (FN) (r (2) = 0.83; p
      < 0.001) and the total hip (TH) (r (2) = 0.89; p < 0.001). The diagnostic
      agreement of the FN and TH regions was significant in all study groups ranging
      from 0.69 to 0.76 (p < 0.001). For the final diagnosis, which is based on the
      least T-score of the FN or TH regions, the diagnostic agreement was 0.73 for all
      women, 0.77 for perimenopausal women, 0.73 for postmenopausal women, 0.70 for
      postmenopausal women age less than 65 years and 0.71 for postmenopausal women age
      greater than or equal to 65 years. The percentage of misclassification for all
      women was 16.9 %, with 3.3 % being downgraded from normal to LBM and 3.4 % from
      LBM to OP. CONCLUSION: Despite the fact that good diagnostic agreement was
      demonstrated in this study, a significant number of diagnostic discordance
      between left and right hips (16.9 %) was also observed. BMD measurements of both
      hips are recommended for diagnosing LBM and OP in clinical practice.

PMID- 22865409
TI  - Non-redox-metal-catalyzed redox reactions: zinc catalysts.
AB  - The advantages of zinc catalysts, such as their low toxicity, low cost, and
      environmentally benignity, are encouraging organic chemists to explore their
      applications in organic synthesis. As a non-redox metal, zinc catalysts have been
      investigated in redox reactions over the past few decades. Because of the
      importance of redox reactions, the interest in zinc catalysts, and the fact that
      no review on zinc-catalyzed redox reactions has been published, herein, I have
      collected and summarized the main contributions in this area. This review is
      divided into two parts: reduction reactions and oxidation reactions.

PMID- 22865408
TI  - Cortical networks for ethologically relevant behaviors in primates.
AB  - Parietal-frontal networks in primate brains are central to mediating actions.
      Physiological and anatomical investigations have shown that the parietal-frontal
      network is consistently organized across several branches of primate evolution
      that include prosimian galagos, New World owl and squirrel monkeys, and Old World
      macaque monkeys. Electrical stimulation with 0.5-sec trains of pulses delivered
      via microelectrodes evoked ethologically relevant actions from both posterior
      parietal cortex (PPC) and frontal motor cortex (FMC). Reaching, grasping,
      defensive, and other complex movement patterns were evoked from domains that had
      a characteristic organization in both FMC and PPC. Although a PPC domain (e.g.
      reaching) may be connected with other PPC domains (e.g. grasping and defensive),
      its connections with FMC are preferential for a matching domain (reaching).
      Similarly, electrical stimulation of a PPC domain and concurrent optical imaging
      of FMC, showed activation patterns consistent with the preferential connectivity
      of PPC and FMC domains. The evidence for similar arrangements of interconnected
      functional domains in PPC and FMC of members of three major branches of the
      primate radiation suggests that the parietal-frontal networks emerged early in
      the evolution of primates. The small size of PPC in the close relatives of
      primates including lagomorphs, rodents, and tree shrews, suggests a limited
      involvement of PPC in motor behavior before archaic primates emerged. However,
      functional domains may have evolved in motor cortex before the emergence of
      archaic primates.

PMID- 22865410
TI  - Prague--setting the scene for the 4th EuCheMS Chemistry Congress.

PMID- 22865412
TI  - Quadruple domino organocatalysis: an asymmetric aza-Michael/Michael/Michael/aldol
      reaction sequence leading to tetracyclic indole structures with six
      stereocenters.

PMID- 22865414
TI  - New, fast, clinical vestibular tests identify whether a vertigo attack is due to
      early Meniere's disease or vestibular neuritis.

PMID- 22865415
TI  - Classification of congenital vascular malformations: the last challenge for
      congenital vascular malformations.

PMID- 22865416
TI  - Unusual localization of a primary superficial venous aneurysm: a case report.
AB  - OBJECTIVES: Primary aneurysms of superficial venous system are rare and
      frequently misdiagnosed as varicose veins. Clinical presentation is variable
      depending on the presence of compression to surrounding structures. We report a
      rare case of primary cephalic vein aneurysm presented with wrist pain due to
      radial nerve compression. METHOD/CASE: A 61-year-old woman was admitted with
      right wrist pain and localized mass. Physical and imaging examinations showed a
      localized cephalic vein aneurysm compressing radial nerve. Simple excision was
      performed successfully. RESULTS: Cosmetic and clinical results at the first month
      follow-up were successful. DISCUSSION: Although primary superficial venous
      aneurysms of upper extremities are very rare, the treatment of choice is most
      commonly same as the ones in lower limbs. Simple excision is the best approach in
      the most of the cases, while sclerotherapy could be preferred in order to obtain
      better cosmesis or to avoid injuries to surrounding structures.

PMID- 22865417
TI  - Anticoagulation therapy for postoperative deep vein thrombosis coupled with
      pulmonary embolism: a potential trigger for delayed popliteal artery injury
      presentation after total knee arthroplasty.
AB  - OBJECTIVES: A case of delayed popliteal artery injury (PA-INJ) onset after total
      knee arthroplasty (TKA) in a patient under postoperative anticoagulation therapy
      is reported. The role of anticoagulation both in late PA-INJ presentation and in
      PA-INJ management is discussed. REPORT: An obese 76-year-old woman was presented
      with a common femoral vein thrombosis coupled with pulmonary embolism five days
      after TKA. She was immediately placed under anticoagulation therapy. Four days
      later, during physiotherapy-supervised mobilization, she developed a calf
      haematoma and large retro-articular pseudoaneurysm. Angiography revealed a minor
      PA-INJ successively treated with a covered stent-graft. CONCLUSIONS: In cases of
      initially undetected and staunched TKA-related PA-INJs, postoperative
      anticoagulation therapy may act as a potential trigger for final arterial rupture
      during mobilization exercises, followed by acute bleeding; in these cases,
      endovascular management represents an excellent treatment option. Close clinical
      and instrumental monitoring is strongly recommended after TKA, in patients who
      imperatively require full-dose anticoagulation therapy.

PMID- 22865418
TI  - Telangiectasias resistant to sclerotherapy are commonly connected to a
      perforating vessel.
AB  - Leg telangiectasias resistant to repeated courses of sclerotherapy in patients
      without deep and superficial venous incompetence are not uncommon. Little is
      known about factors which may underlie the resistance. Among 26 patients with
      such telangiectasias we found a direct communication of the vessels with deep and
      saphenous veins in 65% of patients. Ultrasound-guided injection of 0.5%
      polidocanol foam into the feeding veins or their perforating segments led to
      clearance of all the telanagiectasias. In 23% of cases no feeding veins could
      have been identified by ultrasound. Direct injections of a sclerosant into
      perforating feeding veins may clear refractory telangiectasias in a majority of
      patients though it is obvious that other factors may contribute to the failure of
      sclerotherapy in others. 

PMID- 22865419
TI  - Polidocanol foam sclerotherapy of persisting postoperative seromas after varicose
      vein surgery: a series of six cases.
AB  - OBJECTIVE: The aim of our case series was to show the therapeutic effect and the
      safety of the use of polidocanol foam in ultrasound-guided sclerotherapy
      treatment of relatively small postoperative seromas after varicose vein surgery.
      METHODS: We treated six patients with postoperative seromas after varicose vein
      surgery that were refractory to conventional treatments including compression
      dressings, repeated needle aspirations and manual lymph drainage. RESULTS: A
      complete regression of the fluid collections was seen after one and two
      ultrasound-guided injections of polidocanol foam into the seroma cavity in two
      cases, respectively. Up to five treatment sessions and up to four further needle
      aspirations were necessary for the remaining two patients until complete
      regression of the seromas. No side-effects were reported. CONCLUSION: This is the
      first case series to report of the regression of postoperative seromas after
      varicose vein surgery induced by polidocanol foam sclerotherapy.

PMID- 22865420
TI  - Radiofrequency-induced thermal therapy: results of a European multicentre study
      of resistive ablation of incompetent truncal varicose veins.
AB  - OBJECTIVES: To investigate the effectiveness of bipolar radiofrequency-induced
      thermal therapy (RFITT) in a multicentre non-randomized study. METHODS: Some 672
      incompetent saphenous veins (85% great saphenous varicose vein, 15% short
      saphenous vein) in 462 patients (56.5% CEAP [clinical, aetiological, anatomical
      and pathological elements] class 3 or worse) were treated in eight European
      centres. Patients were assessed between 180 and 360 days postoperatively.
      Occlusion rates were determined by duplex ultrasound and compared with the power
      used for treatment, pull back rate and experience of the operating surgeon.
      RESULTS: Complete occlusion rates of 98.4% were achieved when treatments were
      performed by an experienced operator (more than 20 cases), when the maximum power
      setting on the RFITT generator was between 18 and 20 W and the applicator was
      withdrawn at a rate slower than 1.5 second/cm CONCLUSIONS: RFITT is efficacious,
      well tolerated by patients and has a low incidence of procedure-related post
      operative complications.

PMID- 22865421
TI  - Duplication of the superior vena cava associated with atrial termination of the
      left hepatic vein.
AB  - Duplication of the superior vena cava (SVC), associated with an aberrant left
      hepatic vein (LHV), was found in one of the 58 dissected specimens. The right SVC
      virtually showed a typical appearance. The persistent left SVC, which drained
      into the right atrium via the enlarged coronary sinus, was formed by the
      persistence of the left anterior cardinal vein. The LHV opened into the right
      atrium, due to the persistent left hepatocardiac channel. The left common carotid
      artery arose from the brachiocephalic trunk as a consequence of a regression of
      the embryonic aortic sac. The revealed venous and arterial variations seem to be
      the first reported vascular combination of this type. 

PMID- 22865422
TI  - Regulation of MU-opioid type 1 receptors by microRNA134 in dorsal root ganglion
      neurons following peripheral inflammation.
AB  - BACKGROUND: MOR1 is the main transcript of MU-opioid receptor (MOR) gene, which
      represents a mandatory molecule for the analgesic effects of opioids and plays an
      important role in the pathology of inflammatory pain. MicroRNAs (miR) are non
      coding molecules that primarily modulate gene expression at the post
      transcriptional level in various pathophysiological conditions. Based on in
      silico analysis, an exact match to the seed sequence of miR-134 was found in 3'
      untranslated region of MOR1. Given the important roles of MOR1 in pain
      modulation, the purpose of this study is to investigate whether miR-134 can
      regulate the MOR1 following allodynia. METHODS: Using Freund's adjuvant (CFA)
      induced chronic inflammatory pain model, we investigated the expression profiles
      of miR-134 and MOR1 in rat dorsal root ganglia (DRG) using quantitative real-time
      polymerase chain reaction, in situ hybridization and immunohistochemistry,
      respectively. The relationship of miR-134 and MOR1 expressions was analysed by
      linear regression. Luciferase assay was used to examine whether MOR1 was the
      target of miR-134. RESULTS: Our results showed that miR-134 expression level was
      inversely related to MOR1 expression. Down-regulation of miR-134 and up
      regulation of MOR1 in the same tissues after inflammatory pain were observed.
      Functional experiments showed that MOR1 expression in SH-SY5Y cells was up
      regulated after inhibition of miR-134, indicating that MOR1 was a target of miR
      134. CONCLUSIONS: Our present data suggested a model that miR-134 participated in
      CFA-induced inflammatory pain by balancing the expression of MOR1 in DRGs, which
      implied that miR-134 may be a potential therapeutic target for the treatment of
      neuropathic pain including inflammation.

PMID- 22865423
TI  - Prognostic value of CT coronary angiography in diabetic and non-diabetic subjects
      with suspected CAD: importance of presenting symptoms.
AB  - AIM: To assess the prognostic relevance of 64-slice computed tomography coronary
      angiography (CT-CA) and symptoms in diabetics and non-diabetics referred for
      cardiac evaluation. METHODS: We followed 210 patients with diabetes type 2 (DM)
      and 203 non-diabetic patients referred for CT-CA for ruling out coronary artery
      disease (CAD). Patients were without known history of CAD and were divided into
      four categories on the basis of symptoms at presentation (none, atypical angina,
      typical angina and dyspnoea). Clinical end points were major cardiac events
      (MACE): cardiac-related death, non-fatal myocardial infarction, unstable angina
      and cardiac revascularizations. Cox proportional hazard models, with and without
      adjustment for risk factors and multiplicative interaction term (obstructive CAD
      * DM), were developed to predict outcome. RESULTS: DM patients with dyspnoea or
      who were asymptomatic showed a higher prevalence of obstructive CAD than non
      diabetics (p <= 0.01). At mean follow-up of 20.4 months, DM patients had worse
      cardiac event-free survival in comparison with non-DM patients (90% vs. 81%, p =
      0.02). In multivariate analysis, CT-CA evidence of obstructive CAD (in DM
      patients: HR: 6.4; 95% CI: 2.3-17.5; p < 0.001; in non-DM patients: HR: 7.4; 95%
      CI: 2.1-26.7; p = 0.002) and the presence of typical angina (in DM patients: HR:
      2.9; 95% CI: 1.3-6.3; p = 0.007; in non-DM patients: HR: 2.7; 95% CI: 1.1-7.1; p
      = 0.03) were independent predictors of MACE in both groups. Furthermore, other
      independent outcome predictors included dyspnoea (HR: 3.8; 95% CI: 1.7-8.5; p =
      0.001), the number of segments with any CAD (HR: 1.1; 95% CI: 1.001-1.2; p =
      0.04) in DM patients and coronary calcium score >100 in non-DM patients (HR: 5.6;
      95% CI: 1.4-21.5; p = 0.01). In Cox regression analysis of the overall
      population, interaction term obstructive CAD * DM resulted in non-significance.
      CONCLUSIONS: Among DM patients, dyspnoea carried a high event risk with a MACE
      rate four times higher. CT-CA findings were strongly predictive of outcome and
      proved valuable for further risk stratification.

PMID- 22865424
TI  - Magnetic resonance assessment of left ventricular volumes and mass using a single
      breath-hold 3D k-t BLAST cine b-SSFP in comparison with multiple-breath-hold 2D
      cine b-SSFP.
AB  - OBJECTIVE: To assess the feasibility of single-breath-hold three-dimensional cine
      b-SSFP (balanced steady-state free precession gradient echo) sequence (3D-cine),
      accelerated with k-t BLAST (broad-use linear acquisition speed-up technique),
      compared with multiple-breath-hold 2D cine b-SSFP (2D-cine) sequence for
      assessment of left ventricular (LV) function. METHODS: Imaging was performed
      using 1.5-T MRI (Achieva, Philips, The Netherlands) in 46 patients with different
      cardiac diseases. Global functional parameters, LV mass, imaging time and
      reporting time were evaluated and compared in each patient. RESULTS: Functional
      parameters and mass were significantly different in the two sequences [3D end
      diastolic volume (EDV) = 129 +/- 44 ml vs 2D EDV = 134 +/- 49 ml; 3D end-systolic
      volume (ESV) = 77 +/- 44 ml vs 2D ESV = 73 +/- 50 ml; 3D ejection fraction (EF) =
      43 +/- 15% vs 2D EF = 48 +/- 15%; p < 0.05], although an excellent correlation
      was found for LV EF (r = 0.99). Bland-Altman analysis showed small confidence
      intervals with no interactions on volumes (EF limits of agreement = 2.7; 7.6;
      mean bias 5%). Imaging time was significantly lower for 3D-cine sequence (18 +/-
      1 s vs 95 +/- 23 s; p < 0.05), although reporting time was significantly longer
      for the 3D-cine sequence (29 +/- 7 min vs 8 +/- 3 min; p < 0.05). CONCLUSIONS: A
      3D-cine sequence can be advocated as an alternative to 2D-cine sequence for LV EF
      assessment in patients for whom shorter imaging time is desirable.

PMID- 22865425
TI  - Experimental confirmation that vibrations at soft tissue conduction sites induce
      hearing by way of a new mode of auditory stimulation.
AB  - BACKGROUND: A new mode of auditory stimulation has been demonstrated which is
      through soft tissue conduction (STC). It involves evoking auditory sensations by
      applying the clinical bone vibrator to the skin over soft tissue (not over bone)
      sites on the head and neck. METHODS: This study was designed to show that
      stimulation by STC excites the cochlea in a way similar to that of air conduction
      (AC) and bone conduction (BC). RESULTS: It is shown here that auditory nerve
      brainstem evoked response (ABR) thresholds in mice and in the fat sand rat to AC,
      to BC and to STC stimulation are all elevated following administration of drugs
      (salicylic acid and furosemide) which depress the cochlear amplifier. In
      addition, the present study brings evidence that STC stimulation is not a variant
      of BC since the sound pressures recorded in the occluded external auditory canal
      (the occlusion effect) in response to STC are significantly smaller than that to
      BC stimulation, though both are of equal loudness. CONCLUSIONS: This new mode,
      STC, therefore appears to bypass the middle ear mechanisms and consequently may
      contribute to auditory diagnosis.

PMID- 22865426
TI  - Binaural masking level difference in skilled reading children and children with
      dyslexia.
AB  - BACKGROUND: Combining stimuli arriving at both ears makes it possible to locate
      sounds in the environment and to better detect signals or understand speech in
      noise when the sound sources are separated spatially. The sensitivity of the
      binaural system to interaural differences in time and amplitude can be
      investigated by means of the binaural masking level difference (BMLD). The age at
      which the BMLD reaches adult levels appears to depend partly upon masker
      bandwidth. Less is known about the effect of masker's level on the development of
      BMLD in children. In the present study we assessed the effect of masker level on
      the BMLD of 3rd and 5th grade skilled reading children. In view of possible
      binaural hearing effects in dyslexia, the BMLD of a group of 5th grade children
      with reading difficulties was measured. METHODS: Detection thresholds of 500 Hz
      pure tone were measured at noise levels of 40 dBHL, 50 dBHL and 60 dBHL. RESULTS:
      All subjects presented increased MLD values with the rise of noise intensity
      between 40 dBHL and 60 dBHL. Among the skilled readers the results showed that
      younger children had smaller BMLDs than older children at all masker levels.
      However, a significant group-by-intensity interaction indicated that although the
      reading disabled group had reduced BMLD values than older skilled readers at
      noise levels of 50 dBHL and 60 dBHL, no difference was found between their BMLD
      values and those of the young skilled readers at noise levels of 50 dBHL and 60
      dBHL. Moreover, their BMLD values at noise level of 40 dBHL were higher than
      those of the 3rd grade typically reading students while no difference was found
      between them and 5th grade efficient readers. CONCLUSIONS: These results support
      the existence of both quantitative and qualitative differences in binaural
      hearing of children with developmental dyslexia.

PMID- 22865427
TI  - Rate change detection of frequency modulated signals: developmental trends.
AB  - BACKGROUND: The aim of this study was to examine developmental trends in rate
      change detection of auditory rhythmic signals (repetitive sinusoidally frequency
      modulated tones). METHODS: Two groups of children (9-10 years old and 11-12 years
      old) and one group of young adults performed a rate change detection (RCD) task
      using three types of stimuli. The rate of stimulus modulation was either constant
      (CR), raised by 1 Hz in the middle of the stimulus (RR1) or raised by 2 Hz in the
      middle of the stimulus (RR2). RESULTS: Performance on the RCD task significantly
      improved with age. Also, the different stimuli showed different developmental
      trajectories. When the RR2 stimulus was used, results showed adult-like
      performance by the age of 10 years but when the RR1 stimulus was used performance
      continued to improve beyond 12 years of age. CONCLUSIONS: Rate change detection
      of repetitive sinusoidally frequency modulated tones show protracted development
      beyond the age of 12 years. Given evidence for abnormal processing of auditory
      rhythmic signals in neurodevelopmental conditions, such as dyslexia, the present
      methodology might help delineate the nature of these conditions.

PMID- 22865428
TI  - Left anterior descending/right coronary artery as culprit arteries in acute
      myocardial infarction (n=2011) in changing physical environment, percutaneous
      coronary intervention data, 2000-2010.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is one of the principal
      treatments of acute coronary syndrome (ACS), including acute myocardial
      infarction (AMI). This treatment largely expanded our knowledge on the
      pathophysiology of AMI and related coronary pathologies. Recent studies found a
      significant relationship of the timing of ACS with environmental physical
      activity: solar (SA), geomagnetic (GMA) and cosmic ray (CRA) activity. The aim of
      this study was to examine if the interrelationship of two principal culprit
      arteries, left anterior descending (LAD) and right coronary artery (RCA), are
      involved in the pathogenesis of AMI in different daily levels of GMA and CRA.
      METHODS: Patients undergoing PCI for AMI on the day of symptoms of the disease
      (n=2011, 79.9% males) in the Rabin Medical Center in the years 2000-2010 were
      studied. The culprit arteries, LAD and RCA, correlated to AMI in zero and I0-IV0
      of daily GMA and inversely to GMA related CRA (measured by neutron activity on
      the earth surface) and their ratio was compared. RESULTS: LAD (45.0%) and RCA
      (35.7%) were the main culprit arteries in AMI. LAD/RCA ratio increased inversely
      to GMA (zero=IV0, r=-0.94, p=0.017) and in correlation with daily neutron
      activity for LAD (r=0.97, p=0.03) and RCA (r=0.95, p=0.04). LAD/RCA ratio was 1
      in IV0 of GMA (28% increase) and steadily increased to 1.62 (62% difference) at
      zero GMA (r=-0.94, p=0.0117), and increasing neutron activity was accompanied by
      increasing LAD involvement as a culprit artery in AMI. CONCLUSIONS: High daily
      neutron activity and low GMA are accompanied by increasing LAD as a culprit
      artery in AMI. The possible mechanisms of this finding are discussed.

PMID- 22865429
TI  - Changes in ECG pattern with advancing age.
AB  - BACKGROUND: The rising prevalence of cardiovascular disease with advancing age
      can be attributed to the cumulative effect of the normal aging process and
      cardiovascular risk factor. Another factor to consider is the changing age
      structure of the population. The normal aging process is associated with
      extensive changes throughout the cardiovascular system that influence the
      epidemiology, clinical features, response to therapy and prognosis of
      cardiovascular diseases in older adults. Thus, there is a need for evaluation of
      cardiac status of the elderly population. METHODS: The resting electrocardiogram
      (ECG) permits us to suspect or diagnose a large number of cardiac disorders. As a
      non-invasive, less expensive and simple technique, the ECG can be even more
      useful in developing countries, such as India where resources are limited and
      cardiovascular diseases are rapidly emerging as a major health problem. The
      present study was carried out in 400 apparently healthy asymptomatic subjects
      (age range: 45-74 years) selected from the general population of Solapur city.
      All these subjects were screened for prevalence of various ECG abnormalities in
      relation to age by recording resting 12-lead electrocardiogram. ECGs were coded
      and classified as abnormal, according to the Minnesota code system. RESULTS: This
      study has outlined the overall relationship between the electrocardiographic
      abnormalities and advancing age. Indeed, the close parallel relationship between
      the incidence of abnormal ECG and advancing age found in our study suggests that
      the ECG can be a highly reliable indicator of heart disease even in sixth or
      seventh decades when the validity of other parameters, such as history or
      symptoms is often diminished. CONCLUSIONS: In summary, the ECG in apparently
      healthy asymptomatic subjects identifies subgroups at high risk of cardiovascular
      diseases. Thus, the resting ECG is an office-based test capable of identifying
      symptomless heart disease and determining which patient should be referred for
      further non-invasive testing or cardiac catheterization.

PMID- 22865430
TI  - The effects of docosahexaenoic acid supplementation and exercise on growth
      hormone and insulin-like growth factor I serum levels during chronic hypoxia in
      rats.
AB  - BACKGROUND: In this study we examined the effects of docosahexaenoic acid (DHA)
      on growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin-like
      growth factor binding protein-3 (IGFBP-3) in response to chronic hypoxia and
      exercise training in hypoxic conditions. METHODS: Thirty-five rats were divided
      into five groups; control group (C), hypoxia group (H), hypoxia-exercise group
      (HE), hypoxia-docosahexaenoic acid group (HD), hypoxia-exercise-docosahexaenoic
      acid group (HED). A treadmill exercise was performed as 30 m/min for 20 min/day,
      5 days per week for 28 days at level grade for the exercising groups (HE and
      HED). DHA was given to the HD and HED groups every day orally (36 mg/kg). The
      animals, except for the C group, were exposed to hypoxia for 28 days. RESULTS:
      Serum levels of GH and IGF-I in the H group decreased after chronic hypoxia
      (p<0.001). GH and IGF-I in the HD group also decreased compared with the C group
      (p<0.05, p<0.01, respectively). GH in C group did not show significant difference
      compared with the HE and HED groups. Decreased serum level of IGF-I was observed
      for the HED group (p<0.05). CONCLUSIONS: According to our findings, chronic
      hypoxia exposure decreases serum levels of GH, and IGF-I and exercise training
      have a slightly positive effect on GH/IGF-I axis during hypoxia. In addition, DHA
      supplementation slightly increases GH and IGF-I serum levels in hypoxic
      conditions. However, this effect on GH/IGF-I axis during hypoxia is not strong
      compared with exercise. Therefore, we concluded that exercise and/or DHA
      supplementation does not have additional positive effect on these hormones in
      hypoxic conditions.

PMID- 22865431
TI  - Evaluation of antidepressant activity of ropinirole coadministered with
      fluoxetine in acute and chronic behavioral models of depression in rats.
AB  - BACKGROUND: Certain unknown aspects of ropinirole action, such as its
      antidepressant effect after chronic administration and on cotreatment with
      fluoxetine, remain to be evaluated, which formed the rationale for this study.
      METHODS: Wistar rats of either sex (weighing 150-200 g) were used. In the dose
      finding study, oral dose of ropinirole (20 mg/kg) was selected. This was combined
      with two different doses of fluoxetine (10 and 20 mg/kg). Their antidepressant
      like effects were compared in acute and chronic forced-swim test (FST). Acute FST
      was conducted in two sessions after administration of three doses within 24 h.
      Chronic FST was conducted over 14 days. Drugs were administered each day for 14
      days. Effect on locomotor activity was tested in OFT. RESULTS: ANOVA with post
      hoc Tukey test was used. Dose-finding study of ropinirole showed that out of
      three doses, 20 mg/kg produced maximum reduction in immobility in acute FST
      (137+/-8 s). Coadministration of ropinirole with fluoxetine in acute FST further
      reduced immobility (107+/-8 s). This effect was more prominent in chronic forced
      swim-stressed rats (74+/-2 s). Neither ropinirole nor its coadministration with
      fluoxetine increased locomotor activity in open-field test. CONCLUSIONS: The
      potential of ropinirole to act as an antidepressant agent is proven by the
      reduction in immobility time in FST. Further, there is an augmentation of the
      effect of fluoxetine by ropinirole, suggesting synergistic interaction of
      dopamine and serotonin pathway in brain.

PMID- 22865432
TI  - The effect of cypermethrin on different tissues of freshwater fish Tilapia
      mossambica (Perters).
AB  - BACKGROUND: Environmental pollution is one of the most serious problems mankind
      is facing in this century. Arthropods and fish are highly sensitive to synthetic
      pyrethroids. In this article, we describe the acute toxicity, free amino acid
      level and protease activity in the tissues of freshwater fish when exposed to
      cypermethrin. METHODS: Acute toxicity of cypermethrin to the freshwater fish
      Tilapia mossambica was studied using a static bioassay method. The effect of
      cypermethrin on free amino acid and protease activity in tissues of gills, liver
      and muscle of freshwater fish Tilapia mossambica was also studied. RESULTS: The
      LC50 in 96 h was found to be 35.6 MUg/L. Free amino acid levels and protease
      activity showed an elevation following exposure to lethal and sub lethal doses of
      cypermethrin. A significant change was noticed on day 4 increase. However, normal
      condition was restored only in sub lethal concentration. CONCLUSIONS: The present
      study clearly shows significant changes in the Tilapia mossambica when exposed to
      a low quantity of cypermethrin.

PMID- 22865433
TI  - In vitro antibacterial activity of nanoconjugated vancomycin against plasmid
      mediated intraspecies and interspecies transfer of vancomycin resistance.
AB  - BACKGROUND: The aim of the present study was to observe the plasmid mediated
      intraspecies and interspecies transfer of vancomycin resistance, and possible
      antibacterial activity of nanoconjugated vancomycin against such resistant.
      METHODS: Plasmids were isolated from a chosen vancomycin resistant Staphylococcus
      aureus strain (MMC-17). The obtained 890 bp plasmid was then transferred to
      vancomycin sensitive S. aureus (MMC-6) and Escherichia coli (RGK 26) strains.
      RESULTS: The vancomycin sensitive S. aureus and E. coli developed vancomycin
      resistance. Plasmid analysis of the transformed MMC-6 and RGK 26 revealed that it
      contains 890 bp plasmid corresponding to the donor S. aureus, which may harbor
      the vanA gene. Nanoconjugated vancomycin shows its efficient drug action through
      transport of vancomycin into transformed MMC-6 and RGK 26. CONCLUSIONS: Plasmid
      mediated intraspecies and interspecies transfer of vancomycin resistance is
      accomplished by the vanA gene. Nanoconjugated vancomycin shows effective drug
      delivery in plasmid mediated vancomycin resistance in S. aureus and E. coli.

PMID- 22865434
TI  - Pro-healing effects of morin, a natural antioxidant, on normal and dexamethasone
      impaired wounds.
AB  - BACKGROUND: The aim of the study was to investigate the effects of morin on skin
      breaking strength, hydroxyproline, lysyl oxidase, DNA and RNA content of
      experimentally inflicted wounds in rats. METHODS: This study was performed on
      albino rats of either sex at the Central Animal Research Facility (CARF), Manipal
      University. RESULTS: Morin showed significant wound contraction on day 7 as
      compared to control with mean closure of 47.44+/-6.07% in excision wound model.
      Granulation tissue breaking strength was significantly increased (p<0.05) in the
      morin treated group with 180.2+/-7.94 g when compared to control at 151.2+/-6.99
      g. There was a significant increase in hydroxyproline content with the morin
      treated group when compared to control with 3.41+/-0.33 MUg/mg of granulation
      tissue. Similarly, the wound parameters were improved with the morin treated
      group in dexamethasone delayed healing. CONCLUSIONS: Our results suggest that
      morin treatment accelerates the healing process delayed by concurrent use of
      steroids.

PMID- 22865435
TI  - Effects of nimesulide on testicular functions in prepubertal albino rats.
AB  - BACKGROUND: Daily consumption of painkillers has almost become a routine in many
      parts of Africa and Asia due to manual labor, especially in young adults. In view
      of the wide-scale use of painkillers in many parts of Africa and Asia, it is
      feared that the use of nimesulide may constitute an appreciable public health
      risk. The present work is aimed at assessing the long-term testicular toxicity of
      nimesulide in growing male albino rats. METHODS: Male albino rats aged 4-5 weeks
      and weighing between 36 and 42 g were obtained from the Toxicology Unit of the
      Department of Pharmacology, Faculty of Pharmacy University of Nigeria, Nsukka,
      Nigeria. The animals were housed singly in a cross-ventilated room at a
      temperature 22 degrees C+/-3 degrees C and a 12-h light/12-h dark cycle. They
      were fed with standard rat pellets (Pfizer Pharmaceuticals, Ikeja, Nigeria) and
      were given water ad libitum. The rats were divided into three groups of five rats
      each: the first and second groups orally received 5 and 7.5 mg/kg/day of
      nimesulide, respectively, whereas the third group did not receive any drug and
      acted as controls for 56 days. Weekly body weight of each rat was taken. Blood
      samples were collected on the 56th day by cardiac puncture, and serum samples
      were frozen until analysis. Rats were sacrificed under ether anesthesia.
      Epididymal semen number was counted using a Neubauer counting chamber. Sperm
      motility was assayed microscopically within 5 min at 37 degrees C. Estradiol and
      testosterone were analyzed with electrochemiluminescence immunoassay using
      Elecsys autoanalyzer, model 1010 (Roche, Mannheim, Germany). The testes were
      excised, weighed, and fixed in Bouin fluid and processed for histopathology.
      RESULTS: Treatment with nimesulide did not significantly affect body weight,
      absolute and relative testis weights, or epididymal sperm number, but there were
      significant differences in testosterone and estradiol levels. At the doses
      studied, there were no significant changes in testicular architecture except for
      mild degenerative changes. CONCLUSIONS: In conclusion, nimesulide at normal
      therapeutic doses may not be spermatoxic, but it is feared that at higher doses,
      it may have testicular toxicity in albino rats.

PMID- 22865436
TI  - Prescription pattern of antidiabetic drugs in the outpatient departments of
      hospitals in Malappuram district, Kerala.
AB  - BACKGROUND: The study aimed to describe the current trends in the prescription
      pattern of antidiabetic drugs in outpatient departments and to assess different
      co-morbid conditions. METHODS: This study was a cross-sectional survey of all
      prescriptions received from 200 outpatients attending different community
      pharmacies of Malappuram district. Prescriptions were collected by taking their
      image. Informed verbal consent was obtained from each patient and inquiries were
      made about their co-morbidities. The contents of the prescriptions were assessed
      on the basis of drugs used for diabetes and brand names were decoded to generic
      names using standard CIMS India and the internet. RESULTS: Among 200
      prescriptions, 95% were for type 2 diabetes mellitus and 5% for type 1 diabetes
      mellitus. Eighty percent were prescribed with oral hypoglycemic agents alone as
      mono or in combination therapy, 5% were with insulin alone and 15% with insulin
      and oral hypoglycemic drug combination. 77% had more than five medicines, in
      which many were multidrug combinations. No prescription contained generic drugs
      and 13% contained at least one vitamin supplement. CONCLUSIONS: The study
      concluded that the choice of antidiabetic drugs was only slightly changed
      compared to previous studies, except for newer sulfonyl ureas, thiazolidinediones
      and improved insulin preparations. Polypharmacy is a big problem, especially for
      elderly patients. This suggests the need for development of evidence-based
      guidelines for specific conditions by independent bodies. The study necessitates
      the need to develop and use a standardized ideal format for all prescriptions.
      Thereby we can, to an extent, reduce the chance of medication errors.

PMID- 22865437
TI  - Orthostatic hypotension in the anesthetized rabbit in the sitting position
      exceeds cerebral autoregulation.
AB  - BACKGROUND: Orthostatic hypotension and cerebral autoregulation have been
      extensively studied in the rabbit. However, these physiologic responses have not
      been previously studied utilizing a rabbit in the sitting position under
      anesthesia. METHODS: This unusual position was obtained as the preferred
      orientation based on geometry requirements of associated equipment for a study of
      osteoarthritis of the knee. Rabbits for this experiment did not survive and an
      additional experimental condition was developed to elucidate the mechanism and
      cause of death. The carotid artery pressure was measured under general anesthesia
      with incremental tilt testing to achieve the sitting position. RESULTS: Under
      this condition, rabbits developed orthostatic hypotension and did not survive.
      CONCLUSIONS: According to previous studies of orthostatic hypotension and limits
      of cerebral autoregulation, it is concluded that orthostatic hypotension in the
      anesthetized rabbit in the sitting position exceeds cerebral autoregulation.

PMID- 22865443
TI  - Two types of cochlear hair cells with two different modes of activation are
      better than one.
AB  - The hair cells are the receptor cells of the inner ear. There is still
      controversy concerning the mechanism of their activation. Studies on the hair
      cells of the bullfrog sacculus have provided much information on the activity of
      hair cells. However, the mammalian cochlea has two different types of hair cells 
      the inner hair cells (IHCs) and the outer hair cells (OHCs) - and it is likely
      that their activation mechanisms are not identical. Mechanical manipulations of
      the cochlea and measurements of the passive and active displacements of the
      basilar membrane in the normal and postmortem cochleas provide evidence that the
      OHCs are activated directly by the fluid pressures induced in the cochlea by low
      level sound, and not indirectly by a passive traveling wave. The activated OHCs
      produce active displacements (the cochlear amplifier) which excite the IHCs,
      probably by deflecting their stereocilia, followed by excitation of the auditory
      nerve fibers.

PMID- 22865444
TI  - Acute myocardial infarction (AMI) (n-11026) on days of zero geomagnetic activity
      (GMA) and the following week: differences at months of maximal and minimal solar
      activity (SA) in solar cycles 23 and 24.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is one of most common
      cardiovascular pathologies in the industrial world. In addition to known risk
      factors, environmental physical activity factors such as solar activity (SA),
      geomagnetic activity (GMA), and cosmic ray activity (CRA) could be also involved
      in the timing of AMI. The aim of this study was to study AMI admissions at days
      of zero GMA, accompanied by high CRA, and the following week in the higher and
      lowest parts of solar cycles 23 and 24. METHODS: Patients admitted for AMI
      (n=11,026, 59.5% men) in years 2000-2009 at the Department of Cardiology of
      Lithuanian University of Medical Sciences were studied for all periods and
      separately for the higher part of the 11-year solar activity in cycles 23 and 24
      (2000-2007) and its lowest part (2008-2009). Admissions at day of zero GMA as
      well as 1, 2, 6, and 7 days after zero-GMA day were compared. RESULTS: At high
      SA, zero-GMA days were rare and isolated (36 in years 2000-2007). They have been
      followed by significant increase in admissions on the following days. In the two
      lowest years of SA 2008-2009, there were 57 days of zero GMA, many of which were
      consecutive and in groups. For the whole solar cycle, there was a more gradual
      increase in AMI from 1 to 2 days after zero-GMA day, and there were significantly
      higher AMI admissions at 6 days after the first zero-GMA day (p=0.018).
      CONCLUSIONS: Zero-GMA/high-neutron activity is followed by increase in AMI
      admissions at the days that follow. The effects are different at high and low
      parts of the 11-year solar cycle.

PMID- 22865445
TI  - Phenolic-rich extracts from selected tropical underutilized legumes inhibit alpha
      amylase, alpha-glucosidase, and angiotensin I converting enzyme in vitro.
AB  - BACKGROUND: In this study, interaction of free and bound phenolic extracts from
      selected tropical underutilized legumes (a popular folklore for the management of
      diabetes and hypertension) with key enzymes linked to type 2 diabetes (alpha
      glucosidase and alpha-amylase) and hypertension (angiotensin I converting enzyme,
      ACE) was assessed. METHODS: The free phenolic extracts of the soybean were
      obtained by extracting powdered legume seeds with 80% acetone, whereas the
      residue was subjected to alkaline and acid hydrolysis before extraction with
      ethyl acetate to obtain the bound extracts. Thereafter, enzyme (alpha-amylase,
      alpha-glucosidase, and ACE) inhibitory studies and antioxidant capacity of the
      extracts were investigated. RESULTS: The free and bound phenolic extracts
      inhibited alpha-amylase, alpha-glucosidase, and ACE activities in a dose
      dependent manner. However, the free phenolic extracts of all the legumes were
      stronger inhibitors of alpha-glucosidase than their corresponding bound phenolic
      extracts. In addition, the free phenolic extracts (except melon) exhibited
      stronger ACE inhibition than their corresponding bound phenolic extracts. All the
      phenolic extracts significantly (p<0.05) inhibited Fe2+-induced oxidative stress
      in the pancreas (in vitro) and exhibited strong antioxidant activities.
      CONCLUSIONS: The inhibition of the alpha-amylase, alpha-glucosidase, ACE, and
      oxidative stress by the phenolic extracts could be a part of the mechanism
      through which these underutilized legumes manage/prevent type 2 diabetes and
      hypertension. However, as revealed by this study, bambara groundnut with the best
      enzyme inhibitory potentials coupled with strong antioxidant properties ranked
      highest, whereas melon seed ranked least.

PMID- 22865446
TI  - Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole
      fruit of Lagenaria breviflora.
AB  - BACKGROUND: This study was designed to investigate the hepatoprotective and in
      vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria
      breviflora (LB) in experimental animals. METHODS: Forty nine Wistar albino rats
      were divided into seven groups of seven. Group I served as the control group;
      rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone;
      Groups III-VI received different concentrations of plant extract (100, 250 and
      500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a
      reference hepatoprotective agent. RESULTS: There was a significant (p<0.05)
      increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the
      serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level
      decreased significantly. Pretreatment with LB extract led to a significant
      (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and
      H2O2generation. The activities of marker enzymes, such as alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
      (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen
      (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II).
      CONCLUSIONS: The present study suggested that treatment with LB extract enhances
      the recovery from CCL4 induced hepatic damage and oxidative stress via its
      antioxidant and hepatoprotective properties.

PMID- 22865447
TI  - Carotenoid lutein protects rats from gastric ulcer induced by ethanol.
AB  - BACKGROUND: Carotenoid lutein was evaluated for antiulcerogenic activity in rats.
      METHODS: Gastric ulcer was induced in fasted rats by oral administration of
      ethanol (95%) (5 mL/kg body weight). Lutein (100 and 250 mg/kg body weight) was
      administered everyday for 5 days prior to alcohol administration. RESULTS: The
      ulcer index which is a measure of the severity of ulcers was found to be reduced
      in lutein-treated groups. Morphological and histopathological examination
      supported the protection of lutein during alcohol-induced damage in rat stomach.
      Antioxidant enzymes, such as catalase, super oxide dismutase, glutathione
      peroxidase as well as glutathione levels, which were found to be reduced in the
      gastric mucosa of alcohol-treated groups, were found to be elevated after lutein
      treatment. CONCLUSIONS: The mechanism of antiulcer activity may be due to the
      inhibition of oxidative stress produced by alcohol by lutein administration.
      These findings suggest the potential therapeutic use of lutein as an effective
      antiulcer agent.

PMID- 22865448
TI  - Quercetin protects against testicular toxicity induced by chronic administration
      of therapeutic dose of quinine sulfate in rats.
AB  - BACKGROUND: Quinine, a rapidly acting blood schizonticide with a long history of
      use for the treatment of malaria, is gradually been implicated in reproductive
      toxicity. METHODS: In this study, testicular and spermatotoxic effects of quinine
      sulfate (QS) following treatment with an oral dose of 10 mg/kg/day (normal
      therapeutic dose) for 8 weeks was investigated in male albino rats. Toxicity was
      evaluated by assessing antioxidant defense capacity and markers of oxidative
      stress and testicular dysfunction in the testes and epididymal sperm. The
      possible ameliorative effect of quercetin (QC), when co-administered with QS, was
      also assessed. RESULTS: Administration of QS induced oxidative stress in rats.
      The activities of superoxide dismutase, catalase, and malondialdehyde (a marker
      of lipid peroxidation) increased (p<0.05) both in the testes and epididymal sperm
      following QS treatment when compared with saline-treated (control) rats. Ascorbic
      acid levels were significantly reduced, with an insignificant decrease in
      glutathione and testosterone levels in the QS-treated rats, when compared with
      control. The spermiogram decreased with increase in total sperm abnormalities in
      QS-treated rats and was associated with histopathological changes. Our results
      revealed that QC significantly ameliorated QS-induced testicular toxicity and
      oxidative stress. CONCLUSIONS: The testicular toxicity of QS is in part due to
      impairment of testicular antioxidant defense, spermatogenesis and enhancement of
      lipid peroxidation. Also, the ability of QC to reverse the deleterious effects of
      QS on the testes and epididymis qualifies it as a potent chemo-protective agent
      against QS-induced reproductive toxicity.

PMID- 22865449
TI  - A modified simple method for determination of serum alpha-tocopherol (vitamin E).
AB  - BACKGROUND: Vitamin E is one of the important antioxidants linked to regulate
      various diseases, such as atherosclerosis, hypertension, and male infertility. A
      relatively simple and economic biochemical modified method has been developed to
      determine serum alpha-tocopherol concentration. METHODS: The current modified
      method is based on previous Baker and Frank method and the method of Martinek by
      using 2,2'-bipyridyl, ferric chloride, and xylene. The complex of ferrous ions
      generated in this reaction with 2,2'-bipyridyl is determined by using a plain
      enzyme-linked immunosorbent assay microplate (non-antibody coated) at 492 nm.
      RESULTS: The standard curve of this new modified method shows a linearity with
      correlation r=0.997 (concentration vs. absorbance). The absorbance of this color
      complex is directly proportional to the alpha-tocopherol concentration. The
      sensitivity of this new modified method has been compared and correlated with
      Baker and Frank method by using 15 human samples (r=0.99, p<0.0001). CONCLUSIONS:
      This simple and economic method may be routinely used to analyze alpha-tocopherol
      concentration in serum.

PMID- 22865450
TI  - RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of
      BRCA1 and 53BP1.
AB  - The tumor suppressor protein BRCA1 localizes to sites of DNA double-strand breaks
      (DSB), promoting repair by homologous recombination through the recruitment of
      DNA damage repair proteins. In normal cells, homologous recombination largely
      depends on BRCA1. However, assembly of the pivotal homologous recombination
      regulator RAD51 can occur independently of BRCA1 in the absence of 53BP1, another
      DNA damage response protein. How this assembly process proceeds is unclear, but
      important to understand in tumor cell settings where BRCA1 is disabled. Here we
      report that RNF8 regulates BRCA1-independent homologous recombination in 53BP1
      depleted cells. RNF8 depletion suppressed the recruitment of RAD51 to DSB sites
      without affecting assembly or phosphorylation of the replication protein RPA in
      neocarzinostatin-treated or X-ray-irradiated BRCA1/53BP1-depleted cells.
      Furthermore, RNF8/BRCA1/53BP1-depleted cells exhibited less efficient homologous
      recombination than BRCA1/53BP1-depleted cells. Intriguingly, neither RNF8 nor its
      relative RNF168 were required for RAD51 assembly at DSB sites in 53BP1-expressing
      cells. Moreover, RNF8-independent RAD51 assembly was found to be regulated by
      BRCA1. Together, our findings indicate a tripartite regulation of homologous
      recombination by RNF8, BRCA1, and 53BP1. In addition, our results predict that
      RNF8 inhibition may be a useful treatment of BRCA1-mutated/53BP1(low) cancers,
      which are considered resistant to treatment by PARP1 inhibitors and of marked
      current clinical interest.

PMID- 22865451
TI  - Cardiac inflammation after local irradiation is influenced by the kallikrein
      kinin system.
AB  - Radiotherapy of intrathoracic and chest wall tumors may lead to exposure of the
      heart to ionizing radiation, resulting in radiation-induced heart diseases
      (RIHD). The main manifestations of RIHD become apparent many years after
      treatment and include cardiomyopathy and accelerated atherosclerosis. This study
      examines the role of the kallikrein-kinin system (KKS) in RIHD by investigating
      the cardiac radiation response in a kininogen-deficient Brown Norway Katholiek
      (BN/Ka) rat model. BN/Ka rats and wild-type Brown Norway (BN) rats were exposed
      to local heart irradiation with a single dose of 18 Gy or 24 Gy and were observed
      for 3 to 6 months. Examinations included in vivo and ex vivo cardiac function,
      histopathology, gene and protein expression measurements, and mitochondrial
      swelling assays. Upon local heart irradiation, changes in in vivo cardiac
      function were significantly less in BN/Ka rats. For instance, a single dose of 24
      Gy caused a 35% increase in fractional shortening in BN rats compared with a 16%
      increase in BN/Ka rats. BN rats, but not BN/Ka rats, showed a 56% reduction in
      cardiac numbers of CD2-positive cells, and a 57% increase in CD68-positive cells,
      together with a 52% increase in phosphorylation of extracellular signal-regulated
      kinase 1/2 (Erk1/2). Local heart irradiation had similar effects on
      histopathology, mitochondrial changes, and left ventricular mRNA levels of NADPH
      oxidases in the two genotypes. These results suggest that the KKS plays a role in
      the effects of radiation on cardiac function and recruitment of inflammatory
      cells. The KKS may have these effects at least in part by altering Erk1/2
      signaling.

PMID- 22865452
TI  - Inactivation of the HIF-1alpha/PDK3 signaling axis drives melanoma toward
      mitochondrial oxidative metabolism and potentiates the therapeutic activity of
      pro-oxidants.
AB  - Cancer cells can undergo a metabolic reprogramming from oxidative phosphorylation
      to glycolysis that allows them to adapt to nutrient-poor microenvironments,
      thereby imposing a selection for aggressive variants. However, the mechanisms
      underlying this reprogramming are not fully understood. Using complementary
      approaches in validated cell lines and freshly obtained human specimens, we
      report here that mitochondrial respiration and oxidative phosphorylation are
      slowed in metastatic melanomas, even under normoxic conditions due to the
      persistence of a high nuclear expression of hypoxia-inducible factor-1alpha (HIF
      1alpha). Pharmacologic or genetic blockades of the HIF-1alpha pathway decreased
      glycolysis and promoted mitochondrial respiration via specific reduction in the
      expression of pyruvate dehydrogenase kinase-3 (PDK3). Inhibiting PDK3 activity by
      dichloroacetate (DCA) or siRNA-mediated attenuation was sufficient to increase
      pyruvate dehydrogenase activity, oxidative phosphorylation, and mitochondrial
      reactive oxygen species generation. Notably, DCA potentiated the antitumor
      effects of elesclomol, a pro-oxidative drug currently in clinical development,
      both by limiting cell proliferation and promoting cell death. Interestingly, this
      combination was also effective against BRAF V600E-mutant melanoma cells that were
      resistant to the BRAF inhibitor vemurafenib. Cotreatment of melanomas with DCA
      and elesclomol in vivo achieved a more durable response than single agent alone.
      Our findings offer a preclinical validation of the HIF-1/PDK3 bioenergetic
      pathway as a new target for therapeutic intervention in metastatic melanoma,
      opening the door to innovative combinations that might eradicate this disease.

PMID- 22865453
TI  - Rab27a supports exosome-dependent and -independent mechanisms that modify the
      tumor microenvironment and can promote tumor progression.
AB  - During progression from single cancer cells to a tumor mass and metastases, tumor
      cells send signals that can subvert their tissue microenvironment. These signals
      involve soluble molecules and various extracellular vesicles, including a
      particular type termed exosomes. The specific roles of exosomes secreted in the
      tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B
      regulate exocytosis of multivesicular endosomes, which lead to exosome secretion,
      in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in
      mammary carcinoma cells decreased secretion of exosomes characterized by
      endocytic markers, but also of matrix metalloproteinase 9, which is not
      associated with exosomes. Rab27a blockade resulted in decreased primary tumor
      growth and lung dissemination of a metastatic carcinoma (4T1), but not of a
      nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization
      of a population of neutrophil immune cells induced by Rab27a-dependent secretion
      of exosomes together with a specific combination of cytokines and/or
      metalloproteinases. Our findings offer in vivo validation of the concept that
      exosome secretion can exert key pathophysiologic roles during tumor formation and
      progression, but they also highlight the idiosyncratic character of the tumor
      context.

PMID- 22865454
TI  - Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of
      melanoma.
AB  - Metastatic spread of melanoma to the central nervous system (CNS) is a common and
      devastating manifestation of disease progression, which, despite its clinical
      importance, remains poorly understood with respect to underlying molecular
      mechanisms. Using a recently developed preclinical model of spontaneous melanoma
      CNS metastasis, we have identified alterations in expression of endothelin
      receptor B (EDNRB) as a potential factor that influences brain metastatic
      potential. Induced overexpression of this gene mediated enhanced overall
      metastatic disease, and resulted in an increased incidence of spontaneous CNS
      metastases. In contrast, the overexpression of other highlighted genes, such as
      BCL2A1, did not affect the incidence of CNS metastases but nevertheless appears
      to facilitate intracranial tumor growth. The prometastatic effect in the CNS
      associated with EDNRB appears to be mediated by the interaction with its ligands
      resulting in enhanced tumor cell proliferation and thus intracranial melanoma
      growth. That EDNRB contributes to melanoma metastasis is underscored by the fact
      that its therapeutic inhibition by the EDNRB-specific inhibitor A192621
      translated into improved outcomes when treating mice with either visceral
      metastases or intracranial tumors. The identification of an influential role of
      EDNRB in CNS melanoma spontaneous metastasis may provide both a target for
      therapeutic intervention as well as a potential prognostic marker for patients
      having an increased predisposition for incidence of CNS melanoma metastases.

PMID- 22865455
TI  - CD133+ melanoma subpopulations contribute to perivascular niche morphogenesis and
      tumorigenicity through vasculogenic mimicry.
AB  - Tumor cell subpopulations that express cancer stem cell markers such as CD133
      (prominin1) or ABCB5 are thought to be crucial for tumor initiation and
      heterogeneity, but their biological significance in melanoma has been
      controversial. Here, we report that CD133(+) and ABCB5(+) subpopulations are
      colocalized in melanomas in perivascular niches that contain CD144 (VE
      cadherin)(+) melanoma cells forming vessel-like channels, a phenomenon termed
      vasculogenic mimicry (VM). RNAi-mediated attenuation of CD133 established its
      critical function in morphogenesis of these perivascular niches as well as in
      melanoma tumorigenicity. Niche-associated genes CD144 and ABCB5 were
      downregulated in tumors derived from CD133 knockdown (KD) melanoma cells compared
      with controls. CD133KD cells also lacked the ability to form CD144(+) VM-like
      channels in a manner that was associated with a depletion of the ABCB5(+) cell
      subpopulation. Finally, CD133 KD cells exhibited poorer tumor growth in vivo.
      Taken together, our findings corroborate models in which CD133(+)/ABCB5(+)
      melanoma cells reside in a complex anastomosing microvascular niche that
      encompasses CD144(+) VM channels as well as authentic endothelial cell-lined
      blood vessels. Further, they indicate that CD133(+) cells act as stem-like cells,
      which drive tumor growth by promoting VM and the morphogenesis of a specialized
      perivascular niche in melanoma.

PMID- 22865456
TI  - NFAT1 supports tumor-induced anergy of CD4(+) T cells.
AB  - Cancer cells express antigens that elicit T cell-mediated responses, but these
      responses are limited during malignant progression by the development of
      immunosuppressive mechanisms in the tumor microenvironment that drive immune
      escape. T-cell hyporesponsiveness can be caused by clonal anergy or adaptive
      tolerance, but the pathophysiological roles of these processes in specific tumor
      contexts has yet to be understood. In CD4+ T cells, clonal anergy occurs when the
      T-cell receptor is activated in the absence of a costimulatory signal. Here we
      report that the key T-cell transcription factor NFAT mediates expression of
      anergy-associated genes in the context of cancer. Specifically, in a murine model
      of melanoma, we found that cancer cells induced anergy in antigen-specific CD4+ T
      cell populations, resulting in defective production of several key effector
      cytokines. NFAT1 deficiency blunted the induction of anergy in tumor antigen
      specific CD4+ T cells, enhancing antitumor responses. These investigations
      identified tumor-induced T-cell hyporesponsiveness as a form of clonal anergy,
      and they supported an important role for CD4+ T-cell anergy in driving immune
      escape. By illustrating the dependence of tumor-induced CD4+ T-cell anergy on
      NFAT1, our findings open the possibility of targeting this transcription factor
      to improve the efficacy of cancer immunotherapy or immunochemotherapy.

PMID- 22865457
TI  - Effective photothermal chemotherapy using doxorubicin-loaded gold nanospheres
      that target EphB4 receptors in tumors.
AB  - Photothermal ablation (PTA) is an emerging technique that uses near-infrared
      (NIR) laser light-generated heat to destroy tumor cells. However, complete tumor
      eradication by PTA therapy alone is difficult because heterogeneous heat
      distribution can lead to sublethal thermal dose in some areas of the tumor.
      Successful PTA therapy requires selective delivery of photothermal conducting
      nanoparticles to mediate effective PTA of tumor cells, and the ability to combine
      PTA with other therapy modalities. Here, we synthesized multifunctional
      doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) that target EphB4, a
      member of the Eph family of receptor tyrosine kinases overexpressed on the cell
      membrane of multiple tumors and angiogenic blood vessels. Increased uptake of
      targeted nanoparticles T-DOX@HAuNS was observed in three EphB4-positive tumors
      both in vitro and in vivo. In vivo release of DOX from DOX@HAuNS, triggered by
      NIR laser, was confirmed by dual-radiotracer technique. Treatment with T
      DOX@HAuNS followed by NIR laser irradiation resulted in significantly decreased
      tumor growth when compared with treatments with nontargeted DOX@HAuNS plus laser
      or HAuNS plus laser. The tumors in 6 of the 8 mice treated with T-DOX@HAuNS plus
      laser regressed completely with only residual scar tissue by 22 days following
      injection, and none of the treatment groups experienced a loss in body weight.
      Together, our findings show that concerted chemo-photothermal therapy with a
      single nanodevice capable of mediating simultaneous PTA and local drug release
      may have promise as a new anticancer therapy.

PMID- 22865459
TI  - The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay
      in drug development and clinical care.
AB  - A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has
      been developed. Blinded clinical trials have shown higher response rates and
      longer survival in groups of patients with acute myelocytic leukemia and
      epithelial ovarian cancer who have been treated with drugs that show high
      apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types
      have shown that the assay will be used frequently by clinicians to determine
      treatment, and when used, results in higher response rates, longer times to
      relapse, and longer survivals. Model economic analyses suggest possible cost
      savings in clinical use based on increased generic drug use and single-agent
      substitution for combination therapies. Two initial studies with drugs in
      development are promising. The assay may help reduce costs and speed time to drug
      approval. Correlative studies with molecular biomarkers are planned. This assay
      may have a role both in personalized clinical therapy and in more efficient drug
      development.

PMID- 22865458
TI  - Candidate pathways for promoting differentiation or quiescence of oligodendrocyte
      progenitor-like cells in glioma.
AB  - Platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitor
      cells (OPC) located within the mature central nervous system may remain
      quiescent, proliferate, or differentiate into oligodendrocytes. Human
      glioblastoma multiforme tumors often contain rapidly proliferating
      oligodendrocyte lineage transcription factor 2 (Olig2)-positive cells that
      resemble OPCs. In this study, we sought to identify candidate pathways that
      promote OPC differentiation or quiescence rather than proliferation. Gene
      expression profiling conducted in both normal murine OPCs and highly
      proliferative Olig2-positive glioma cells identified all the transcripts
      associated with the highly proliferative state of these cells and showed that
      among the various cell types found within the brain, Olig2-positive tumor cells
      are most similar to OPCs. We then subtracted OPC transcripts found in tumor
      samples from those found in normal brain samples and identified 28 OPC
      transcripts as candidates for promoting differentiation or quiescence. Systematic
      analysis of human glioma data revealed that these genes have similar expression
      profiles in human tumors and were significantly enriched in genomic deletions,
      suggesting an antiproliferative role. Treatment of primary murine glioblastoma
      cells with agonists of one candidate gene, Gpr17, resulted in a decreased number
      of neurospheres. Together, our findings show that comparison of the molecular
      phenotype of progenitor cells in tumors to the equivalent cells in the normal
      brain represents a novel approach for the identification of targeted therapies.

PMID- 22865461
TI  - Treatment of post-traumatic cognitive impairments.
AB  - OPINION STATEMENT: * Cognitive impairment is a common consequence of traumatic
      brain injury (TBI) and a substantial source of disability. Across all levels of
      TBI severity, attention, processing speed, episodic memory, and executive
      function are most commonly affected.* The differential diagnosis for post
      traumatic cognitive impairments is broad, and includes emotional, behavioral, and
      physical problems as well as substance use disorders, medical conditions,
      prescribed and self-administered medications, and symptom elaboration. Thorough
      neuropsychiatric assessment for such problems is a prerequisite to treatments
      specifically targeting cognitive impairments.* First-line treatments for post
      traumatic cognitive impairments are nonpharmacologic, including education,
      realistic expectation setting, environmental and lifestyle modifications, and
      cognitive rehabilitation.* Pharmacotherapies for post-traumatic cognitive
      impairments include uncompetitive N-methyl-D-aspartate receptor (NMDA)
      antagonists, medications that directly or indirectly augment cerebral
      catecholaminergic or acetylcholinergic function, or agents with combinations of
      these properties.* In the immediate post-injury period, treatment with
      uncompetitive NMDA receptor antagonists reduces duration of unconsciousness. The
      mechanism for this effect may involve attenuation of neurotrauma-induced
      glutamate-mediated excitotoxicity and/or stabilization of glutamate signaling in
      the injured brain.* During the subacute or late post-injury periods, medications
      that augment cerebral acetylcholinergic function may improve declarative memory.
      Among responders to this treatment, secondary benefits on attention, processing
      speed, and executive function impairments as well as neuropsychiatric
      disturbances may be observed. During these post-injury periods, medications that
      augment cerebral catecholaminergic function may improve hypoarousal, processing
      speed, attention, and/or executive function as well as comorbid depression or
      apathy.* When medications are used, a "start-low, go-slow, but go" approach is
      encouraged, coupled with frequent reassessment of benefits and side effects as
      well as monitoring for drug-drug interactions. Titration to either beneficial
      effect or medication intolerance should be completed before discontinuing a
      treatment or augmenting partial responses with additional medications.

PMID- 22865462
TI  - Early recognition of acutely deteriorating patients in non-intensive care units:
      assessment of an innovative monitoring technology.
AB  - BACKGROUND: Continuous vital sign monitoring has the potential to detect early
      clinical deterioration. While commonly employed in the intensive care unit (ICU),
      accurate and noninvasive monitoring technology suitable for floor patients has
      yet to be used reliably. OBJECTIVE: To establish the accuracy of the Earlysense
      continuous monitoring system in predicting clinical deterioration. DESIGN:
      Noninterventional prospective study with retrospective data analysis. SETTING:
      Two medical wards in 2 academic medical centers. PATIENTS: Patients admitted to a
      medical ward with a diagnosis of an acute respiratory condition. INTERVENTION:
      Enrolled patients were monitored for heart rate (HR) and respiration rate (RR) by
      the Earlysense monitor with the alerts turned off. MEASUREMENTS: Retrospective
      analysis of vital sign data was performed on a derivation cohort to identify
      optimal cutoffs for threshold and 24-hour trend alerts. This was internally
      validated through correlation with clinical events recognized through chart
      review. RESULTS: Of 113 patients included in the study, 9 suffered major clinical
      deterioration. Alerts were found to be infrequent (2.7 and 0.2 alerts per patient
      day for threshold and trend alert, respectively). For the threshold alerts,
      sensitivity and specificity in predicting deterioration was found to be 82% and
      67%, respectively, for HR and 64% and 81%, respectively, for RR. For trend
      alerts, sensitivity and specificity were 78% and 90% for HR, and 100% and 64% for
      RR, respectively. CONCLUSIONS: The Earlysense monitor was able to continuously
      measure RR and HR, providing low alert frequency. The current study provides data
      supporting the ability of this system to accurately predict patient
      deterioration.

PMID- 22865463
TI  - Molecular and cellular mechanisms of antidepressant action.
AB  - A long-standing theory is that brain monoamine signalling is critically involved
      in the mechanisms of antidepressant drug treatment. Theories on the nature of
      these mechanisms commenced with ideas developed in the 1960s that the drugs act
      simply by increasing monoamine availability in the synapse. However, this
      thinking has advanced remarkably in the last decade to concepts which position
      that antidepressant drug action on monoamine signalling is just the starting
      point for a complex sequence of neuroadaptive molecular and cellular changes that
      bring about the therapeutic effect. These changes include activation of one or
      more programmes of gene expression that leads to the strengthening of synaptic
      efficacy and connectivity, and even switching neural networks into a more
      immature developmental state. It is thought that through this increase in
      plasticity, key neural circuits within the limbic system are more easily
      remodelled by incoming emotionally relevant stimuli. This article attempts to
      bring together previous and current knowledge of antidepressant drug action on
      monoamine signalling at molecular and cellular levels, and introduces current
      thinking that these changes interact with neuropsychological processes ultimately
      to elevate mood.

PMID- 22865464
TI  - Neurosurgical treatments of depression.
AB  - The neurosurgical treatment of treatment-resistant depression (TRD) has entered a
      new era with more and more patients being treated with deep brain stimulation
      (DBS) via surgically implanted intracerebral electrodes. Although the mechanisms
      of action of DBS are still not fully understood, preclinical studies are being
      conducted to elucidate how the treatment might work. DBS in its present form can
      be considered as a relatively new neurosurgical treatment for TRD. However, the
      use of neurosurgery in the management of depression has a much longer history
      particularly with ablative procedures but also vagal nerve stimulation. Here, we
      provide a review of the clinical neurosurgical treatments for TRD, with a main
      emphasis on DBS. In addition, we discuss relevant preclinical data that are
      revealing new information about DBS mechanisms.

PMID- 22865465
TI  - Self-assembled smooth muscle cell tissue rings exhibit greater tensile strength
      than cell-seeded fibrin or collagen gel rings.
AB  - In this study, we created self-assembled smooth muscle cell (SMC) tissue rings
      (comprised entirely of cells and cell-derived matrix; CDM) and compared their
      structure and material properties with tissue rings created from SMC-seeded
      fibrin or collagen gels. All tissue rings were cultured statically for 7 days in
      supplemented growth medium (with epsilon-amino caproic acid, ascorbic acid, and
      insulin-transferrin-selenium), prior to uniaxial tensile testing and histology.
      Self-assembled CDM rings exhibited ultimate tensile strength and stiffness values
      that were two-fold higher than fibrin gel and collagen gel rings. Tensile testing
      of CDM, fibrin gel and collagen gel rings treated with deionized water to lyse
      cells showed little to no change in mechanical properties relative to untreated
      ring samples, indicating that the ECM dominates the measured ring mechanics. In
      addition, CDM rings cultured in supplemented growth medium were significantly
      stronger than CDM rings cultured in standard, unsupplemented growth medium. These
      results illustrate the potential utility of self-assembled cell rings as model
      CDM constructs for tissue engineering and biomechanical analysis of ECM material
      properties.

PMID- 22865466
TI  - (-)-Epicatechin-induced calcium independent eNOS activation: roles of HSP90 and
      AKT.
AB  - Cardiovascular disease (CVD) is a leading determinant of mortality and morbidity
      in the world. Epidemiologic studies suggest that flavonoid intake plays a role in
      the prevention of CVD. Consumption of cocoa products rich in flavonoids lowers
      blood pressure and improves endothelial function in healthy subjects as well as
      in subjects with vascular dysfunction such as smokers and diabetics. The vascular
      actions of cocoa follow the stimulation of nitric oxide (NO). These actions can
      be reproduced by the administration of the cocoa flavanol (-)-epicatechin (EPI).
      Previously, using human endothelial cells cultured in calcium-free media, we
      documented EPI effects on eNOS independently of its translocation from the
      plasmalemma. To further define the mechanisms behind EPI-eNOS activation in
      Ca(2+) -deprived endothelial cells, we evaluated the effects of EPI on the
      eNOS/AKT/HSP90 signaling pathway. Results document an EPI-induced
      phosphorylation/activation of eNOS, AKT, and HSP90. We also demonstrate that EPI
      induces a partial AKT/HSP90 migration from the cytoplasm to the caveolar membrane
      fraction. Immunoprecipitation assays of caveolar fractions demonstrate a physical
      association between HSP90, AKT, and eNOS. Thus, under Ca(2+)-free conditions, EPI
      stimulates NO synthesis via the formation of an active complex between eNOS, AKT,
      and HSP90.

PMID- 22865467
TI  - EGFR and PKC are involved in the activation of ERK1/2 and p90 RSK and the
      subsequent proliferation of SNU-407 colon cancer cells by muscarinic
      acetylcholine receptors.
AB  - We have previously shown that muscarinic acetylcholine receptors (mAChRs) enhance
      SNU-407 colon cancer cell proliferation via the ERK1/2 pathway. Here, we examined
      the signaling pathways linking mAChR stimulation to ERK1/2 activation and the
      subsequent proliferation of SNU-407 cells. The inhibition of the epidermal growth
      factor receptor (EGFR) by AG1478 or protein kinase C (PKC) by GF109203X
      significantly reduced carbachol-stimulated ERK1/2 activation and cell
      proliferation. Cotreatment of the cells with AG1478 and GF109203X produced an
      additive effect on carbachol-stimulated ERK1/2 activation, suggesting that the
      EGFR and PKC pathways act in parallel. The p90 ribosomal S6 kinases (RSKs) are
      downstream effectors of ERK1/2 and are known to have important roles in cell
      proliferation. In SNU-407 cells, carbachol treatment induced RSK activation in an
      atropine-sensitive manner, and this RSK activation was decreased by the
      inhibition of either EGFR or PKC. Moreover, the RSK-specific inhibitor BRD7389
      almost completely blocked carbachol-stimulated cell proliferation. Together,
      these data indicate that EGFR and PKC are involved in mAChR-mediated activation
      of ERK1/2 and RSK and the subsequent proliferation of SNU-407 colon cancer cells.

PMID- 22865469
TI  - Superficial wounding model for epidermal barrier repair studies: comparison of
      Erbium:YAG laser and the suction blister method.
AB  - BACKGROUND AND OBJECTIVES: Wound-healing studies use mainly mechanical methods
      for wound induction, which are laborious and difficult to standardize. Objective
      of this study was to evaluate the Erbium:Yttrium-Aluminium-Garnet (Er:YAG) laser
      method as a model of epidermis ablation on human skin in vivo and to compare the
      quality and healing rates of Er:YAG laser and suction blister (SB) wounds.
      MATERIALS AND METHODS: Er:YAG laser and SB wounds were made on the forearms of 10
      healthy volunteers. Post-wounding measurements including wound surface area (WSA)
      from photographs, wound depth from 3D volume analysis, trans-epidermal water loss
      (TEWL), laser doppler blood flow (LDBF), and optical coherence tomography (OCT)
      imaging were made daily over 7 days. Biopsies were taken on Days 4 and 7.
      RESULTS: 3D analysis showed laser wounds to be shallower and more uniform in
      depth than SB: 54 +/- 14 um versus 140 +/- 102 um, respectively, with histology
      demonstrating complete epidermal removal using SB. SB wounds were more variable
      in size with a WSA of 0.47 +/- 0.24 cm(2) compared to 1.17 +/- 0.14 cm(2) for
      laser wounds. Healing rates were similar in both groups, as measured by TEWL,
      LDBF, and WSA. OCT imaging on Days 3-4 revealed new epidermis below the fibrin
      clot, similar to histology, and a visible stratum corneum on Day 7, but no
      apparent epidermal hyperplasia in contrast to histology. CONCLUSION: Compared to
      the SB model, Er:YAG laser achieved rapid standardized epidermal ablation, which
      despite morphological differences, was similar in terms of epidermal
      regeneration/barrier formation.

PMID- 22865468
TI  - Influence of lifestyle factors on inflammation in men and women with type 2
      diabetes: results from the National Health and Nutrition Examination Survey, 1999
      2004.
AB  - BACKGROUND: Type 2 diabetes is associated with low-grade systemic inflammation,
      increasing the risk for various adverse health outcomes. PURPOSE: Our objective
      was to investigate the association between C-reactive protein (CRP), a marker for
      systemic inflammation, and lifestyle factors in a national sample of people with
      type 2 diabetes. METHODS: This study analyzed data from 1,086 men and women with
      diabetes, who completed the 1999-2004 NHANES. Lifestyle factors included diet
      quality, body mass index (BMI), smoking, and physical activity. RESULTS:
      Stratified logistic regression showed that for both men and women, BMI was a
      strong predictor of elevated CRP after adjusting for age, energy intake,
      race/ethnicity, medications, diabetes duration, and glycosylated hemoglobin.
      However, among men, but not among women, the likelihood of elevated CRP increased
      with lower diet quality and physical inactivity. CONCLUSIONS: Among people with
      type 2 diabetes, higher levels of CRP were associated with lower diet quality and
      physical inactivity among men, and with obesity among both men and women.

PMID- 22865470
TI  - Effect of wheat flour characteristics on sponge cake quality.
AB  - BACKGROUND: To select the flour parameters that relate strongly to cake-making
      performance, in this study the relationship between sponge cake quality, solvent
      retention capacity (SRC) profile and flour physicochemical characteristics was
      investigated using 38 soft wheat samples of different origins. Particle size
      average, protein, damaged starch, water-soluble pentosans, total pentosans, SRC
      and pasting properties were analysed. Sponge cake volume and crumb texture were
      measured to evaluate cake quality. Cluster analysis was applied to assess
      differences in flour quality parameters among wheat lines based on the SRC
      profile. RESULTS: Cluster 1 showed significantly higher sponge cake volume and
      crumb softness, finer particle size and lower SRC sucrose, SRC carbonate, SRC
      water, damaged starch and protein content. Particle size, damaged starch,
      protein, thickening capacity and SRC parameters correlated negatively with sponge
      cake volume, while total pentosans and pasting temperature showed the opposite
      effect. CONCLUSION: The negative correlations between cake volume and SRC
      parameters along with the cluster analysis results indicated that flours with
      smaller particle size, lower absorption capacity and higher pasting temperature
      had better cake-making performance. Some simple analyses, such as SRC, particle
      size distribution and pasting properties, may help to choose flours suitable for
      cake making.

PMID- 22865471
TI  - Application of polymerase chain reaction for fetal gender determination using
      cervical mucous secretions in the cow.
AB  - In the current study we aimed to use PCR to investigate the presence of fetal DNA
      in the bovine (Bos taurus) cervical secretions and maternal serum, and to assess
      the effectiveness of this method in fetal gender determination. Pregnant uteri
      and pre-slaughter maternal blood samples were collected from 21 Holstein Frisian
      cows in a local abattoir. Overall, 13 male and 8 female fetuses were included in
      the study. Cervical mucus was sampled at the laboratory. After DNA extraction,
      the PCR amplified a 280 bp fragment from the X-chromosome and a 217 bp fragment
      from the Y-chromosome based on a sex-related polymorphism in the amelogenin
      locus. The presence of fetal Y-chromosome was confirmed in seven out of 13
      cervical mucus samples collected from cows with male fetuses. Overall test
      sensitivity for correct sex determination based on PCR assay on cervical samples
      was equal to 71.4 +/- 2 %. In contrast, no fetal Y-chromosome DNA was detected in
      maternal serum samples from cows with male fetuses. This is the first report on
      validating the presence of fetal DNA material in the bovine cervical mucus and
      its potential usefulness for fetal sexing. Further investigations are needed to
      maximize the accuracy and evaluate the practicality of this approach.

PMID- 22865472
TI  - Association between multifocal electroretinograms, optical coherence tomography
      and central visual sensitivity in advanced retinitis pigmentosa.
AB  - PURPOSE: To investigate the association between automated perimetry, multifocal
      electroretinogram (mfERG) and optical coherence tomography (OCT) measurements in
      patients with advanced retinitis pigmentosa (RP). METHODS: Twenty-five patients
      with advanced RP were included. Central visual field sensitivity (VFS) was
      evaluated using an average of visual sensitivity value at central four test
      points during central 30-2 static automated perimetry. OCT imaging was conducted,
      and the inner and outer segment (IS/OS) line was classified into three groups:
      Group 1, absence; Group 2, partially intact; and Group 3, intact. Central retinal
      thickness (CRT) that is the retinal thickness of central 3.0 mm was also
      evaluated. Average amplitude and implicit time of N1 and P1 in ring 1 and 2 were
      measured on mfERG. Comparisons of VFS, mfERG and OCT among the three subgroups
      were performed following IS/OS integrity. Relationship among VFS, mfERG and CRT
      was evaluated by regression analysis. RESULTS: Group 3 patients with an intact
      IS/OS line showed a better VFS, and amplitude of mfERG response than those of
      Group 1 and 2. VFS and amplitudes of mfERG were correlated significantly with CRT
      in linear regression analysis. CONCLUSIONS: Disrupted IS/OS integrity was
      associated with visual dysfunction which was shown by decreased amplitude of
      mfERG response and reduced central VFS. CRT was significantly correlated with
      amplitude of mfERG response and central VFS. An eye with the more reduced CRT was
      associated with the worse amplitude of mfERG response and central VFS.

PMID- 22865473
TI  - Response properties of slow PIII in the Large (vls) mutant.
AB  - PURPOSE: Mouse mutants for proteins expressed in the dystrophin-glycoprotein
      complex at the photoreceptor terminal have electroretinogram (ERG) b-waves with a
      delayed onset and time course. The b-wave is defined by the sum of PII generated
      by depolarizing bipolar cells and slow PIII generated by Muller glial cells. In
      this study, we evaluated the hypothesis that the abnormalities observed in one of
      these mutants, Large (vls) , are caused by abnormal response properties of slow
      PIII. METHODS: To isolate slow PIII, we crossed the Large (vls) mutant to a mouse
      line (Gpr179 (nob5) ) that lacks the ERG b-wave but maintains normal
      photoreceptor function and in which retinal degeneration does not occur. ERGs
      were recorded to strobe flash stimuli after overnight dark adaptation. RESULTS:
      In comparison with control responses, the a-wave and slow PIII had comparable
      waveforms but were reduced in amplitude in Large (vls) mice. The magnitude of
      this reduction was comparable for these components, and across stimulus
      luminance. There was no stimulus condition where the amplitude of slow PIII was
      larger than control. CONCLUSIONS: The data obtained are inconsistent with the
      idea that the b-wave abnormalities noted in Large (vls) mutant mice are caused by
      abnormal response properties of slow PIII.

PMID- 22865474
TI  - Anterior cingulate integrity: executive and neuropsychiatric features in
      Parkinson's disease.
AB  - Patients with advanced Parkinson's disease (PD) commonly suffer with significant
      executive dysfunction and concomitant visual hallucinations. Although the
      underlying pathophysiology remains poorly understood, numerous studies have
      highlighted the strong association between these neuropsychiatric features,
      suggesting common neural pathways. Although previous neuroimaging studies have
      identified widespread volume loss across a number of cortical regions, to date,
      no studies have utilized proton magnetic resonance spectroscopy to provide
      insights into how neurometabolic changes may relate to such symptoms. Twenty
      patients with PD and 20 healthy controls underwent spectroscopy to determine the
      N-acetyl aspartate/creatine (NAA/Cr) ratio, which reflects the degree of neuronal
      integrity in neurodegenerative diseases. Voxels were obtained from the anterior
      cingulate cortex (ACC), an area critical for a wide range of executive mechanisms
      as well as from a control volume in the posterior cingulate cortex (PCC).
      Compared to controls, patients with PD had lower NAA/Cr ratios in the ACC. In
      turn, lower NAA/Cr ratios significantly correlated with poorer executive function
      on tasks of attentional set-shifting and response inhibition, as well as more
      severe psychotic symptoms and poorer performance on the Bistable Percept
      Paradigm, a neuropsychological probe of visual hallucinations. NAA/Cr ratios were
      significantly lower in hallucinators, compared to nonhallucinators, within the
      ACC, but did not differ in the PCC. These results suggest that loss of neuronal
      integrity within the ACC plays an important role in the pathophysiology
      underlying executive functioning and visual hallucinations in PD. (c) 2012
      Movement Disorder Society.

PMID- 22865475
TI  - Aromaticity-controlled thermal stability of photochromic systems based on a six
      membered ring as ethene bridges: photochemical and kinetic studies.
AB  - Three photochromic compounds--2-butyl-5,6-bis[5-(4-methoxyphenyl)-2
      methylthiophen-3-yl]-1 H-benzo[de]isoquinoline-1,3(2 H)-dione (BTE-NA), 4,5-bis[5
      (4-methoxyphenyl)-2-methylthiophen-3-yl]benzo[c][1,2,5]thiadiazole (BTA), and
      BTTA, which contain naphthalimide, benzothiadiazole, and benzobisthiadiazole as
      six-membered ethene bridges with different aromaticities--were systematically
      studied in solution, sol-gel, and single-crystal states. They exhibit typical
      photochromic performance with considerably high cyclization quantum yields. BTE
      NA, BTA, and BTTA form a typical donor-pi-acceptor (D-pi-A) system with
      significant intramolecular charge transfer (ICT) between HOMO and LUMO upon
      excitation, thus realizing the fluorescence modulation by both photochromism and
      solvatochromism. The three ethene bridges with different degrees of aromaticity
      can provide a systematic comparison of the thermal stability evolution for their
      corresponding closed forms (c-BTE-NA, c-BTA, and c-BTTA). c-BTE-NA shows first
      order decay in various solvents from cyclohexane to acetonitrile. c-BTA only
      shows first-order decay in polar solvents such as chloroform, whereas it is
      stable in nonpolar solvents like toluene. In contrast, the less aromatic property
      of BTTA gives rise to its unprecedented thermal stability in various solvents
      even at elevated temperatures in toluene (328 K). Moreover, the small energy
      barrier between the parallel and antiparallel conformers allows the full
      conversion from BTTA to c-BTTA. In well-ordered crystal states, all three
      compounds adopt a parallel conformation. Interestingly, BTTA forms a twin crystal
      of asymmetric nature with interactions between the electron-rich oxygen atom of
      the methoxy group and the carbon atom of the electron-deficient
      benzobisthiadiazole moiety. This work contributes to the understanding of
      aromaticity-controlled thermal stability of photochromic systems based on a six
      membered ring as an ethene bridge, and a broadening of the novel building blocks
      for photochromic bisthienylethene systems.

PMID- 22865476
TI  - Utilization of cellulose microcapillary tubes as a model system for culturing and
      viral infection of mammalian cells.
AB  - Cryofixation by high-pressure freezing (HPF) and freeze substitution (FS) gives
      excellent preservation of intracellular membranous structures, ideal for
      ultrastructural investigations of virus infected cells. Conventional sample
      preparation methods of tissue cultured cells can however disrupt the association
      between neighboring cells or of viruses with the plasma membrane, which impacts
      upon the effectiveness whereby virus release from cells can be studied. We
      established a system for virus infection and transmission electron microscopy
      preparation of mammalian cells that allowed optimal visualization of membrane
      release events. African horse sickness virus (AHSV) is a nonenveloped virus that
      employs two different release mechanisms from mammalian cells, i.e., lytic
      release through a disrupted plasma membrane and a nonlytic budding-type release.
      Cellulose microcapillary tubes were used as support layer for culturing Vero
      cells. The cells grew to a confluent monolayer along the inside of the tubes and
      could readily be infected with AHSV. Sections of the microcapillary tubes proved
      easy to manipulate during the HPF procedure, showed no distortion or compression,
      and yielded well preserved cells in their native state. There was ample cell
      surface area available for visualization, which allowed detection of both types
      of virus release at the plasma membrane at a significantly higher frequency than
      when utilizing other methods. The consecutive culturing, virus infection and
      processing of cells within microcapillary tubes therefore represent a novel model
      system for monitoring intracellular virus life cycle and membrane release events,
      specifically suited to viruses that do not grow to high titers in tissue culture.

PMID- 22865477
TI  - Leukocyte filtration improves pulmonary function and reduces the need for
      postoperative non-invasive ventilation.
AB  - OBJECTIVES: Leukocyte depletion (LD) has been reported to reduce inflammatory
      damage during cardiopulmonary bypass (CPB). We evaluated the role of LD in
      pulmonary function and inflammatory response. METHODS: Seventy consecutive CABG
      patients were randomized (1:1) to receive LD on both arterial and cardioplegia
      lines (Filters) or standard arterial filters (Controls) during CPB. Estimates of
      pulmonary function, inflammatory and anti-inflammatory cytokines were collected
      pre-, intra- and postoperatively. RESULTS: Hospital mortality, intensive care and
      in-hospital lengths of stay were similar. Although duration of ventilation and
      incidence of pneumonia were comparable, leukodepleted patients showed higher
      PaO2/FiO2 (p-between groups = 0.005; ICU arrival p = 0.023; 24 hours p = 0.039;
      48 hours p<0.001) and lower need for postoperative non-invasive ventilation
      (NIV), (p = 0.029). Moreover, Filters showed lower inflammatory burst at 24 hours
      (IL-6 p<0.001; IL-8 p = 0.002) and 48 hours (IL-6 p = 0.015). This was associated
      with a lower release of the anti-inflammatory IL-10 (p-between groups = 0.030;
      ICU admission p = 0.002; 24 hours p = 0.003). Furthermore, IL-2 concentration
      proved higher in Filters (p-between groups = 0.013; ICU arrival p = 0.029; 24
      hours p = 0.040; 48 hours p = 0.021) in association with lower leukocyte and
      platelet counts at ICU admission. CONCLUSIONS: LD resulted in lower inflammatory
      burst and less need for release of anti-inflammatory cytokines. Although hospital
      outcomes were similar in terms of mortality and length of stay, improvements in
      pulmonary function and reduced need for postoperative NIV support the use of LD.

PMID- 22865478
TI  - Effect of feeding regulation measures for establishing esophageal channel
      function in neoesophagus created with a nitinol artificial esophagus.
AB  - PURPOSE: This study attempted to observe the effect of feeding regulation
      measures (FRM) for the construction of an esophageal channel function in a
      neoesophagus using an artificial nitinol esophagus. METHODS: Experiments were
      divided among groups: group 1, receiving FRM; and group 2, the non-feeding
      regulation measures (NFRM) group. RESULTS: Ten pigs survived for 6 months without
      any complications such as anastomotic leakage. The shedding time of the
      artificial esophagus in group 1 was significantly delayed in comparison with
      group 2 (>180 +/- 0.0 days vs. 75.6 +/- 27.1 days, respectively, p<0.05). In
      group 1, the weight changes at 3 and 6 months postoperation were significantly
      different in comparison with preoperative values (t = 14.86, 9.17 > 2.78,
      respectively; p<0.05). In group 2, the weight changes at 3 and 6 months
      postoperation were significantly different in comparison with preoperative values
      (t = 7.95, 11.37 > 2.78, respectively; p<0.05). CONCLUSIONS: FRM not only
      effectively delayed the shedding time of the artificial esophagus but also played
      a role in protecting the neoesophagus from stenosis, by functioned as a
      bougienage after artificial esophagus sloughing. Therefore, FRM is an effective
      way for establishing a stable eating channel in the neoesophagus when using a
      nitinol composite artificial esophagus to replace the resected segment of an
      intrathoracic esophagus.

PMID- 22865479
TI  - Weight gains and increased blood pressure in outpatient hemodialysis patients due
      to change in acid dialysate concentrate supplier.
AB  - INTRODUCTION: Sodium balance during hemodialysis is predominantly achieved by
      ultrafiltration. The additional effect of diffusional sodium losses and gains
      remains unclear. We recently changed our dialysate acid concentrate supplier, and
      although both concentrates were instructed to be diluted 1:44, we audited the
      practical effects of this change. METHODS: Review of electronic dialysis and
      laboratory records of patients attending a satellite dialysis center. RESULTS: 91
      adult hemodialysis patients, mean age 61.4 +/- 1.7 years, 65% male, 52% diabetic,
      median dialysate sodium machine setting at 137 mmol/l (137-138), following change
      in acid dialysate patients dialyzed against a mean measured dialysate sodium of
      4.8 (95%cCL 3.6-6.1) mmol/l higher than setting. After six weeks, pre-dialysis
      weight increased from 75.5 +/- 1.9 kg to 76.6 +/- 1.9 kg, p<0.001, with increased
      mean weight loss on dialysis from 2.38 +/- 0.1% to 3.28 +/- 0.13%, p<0.001, and
      increase in pre-dialysis mean arterial blood pressure from 91.2 +/- 1.5 mmHg to
      95.4 +/- 1.5 mmHg, p<0.001. Post-dialysis serum sodium increased from 0 (-3 to
      +3) mmol/l to +3 (1 to 5.5) mmol/l compared to pre-dialysis value, p<0.001.
      Monthly symptomatic episodes of intradialytic hypotension fell from 69 to 46.
      After correcting the dialysate sodium setting, blood pressure and weight gains
      resolved over 4 weeks. CONCLUSIONS: Changing dialysate acid concentrates, both
      labeled 1:44 dilution, led to the delivery of a higher dialysate sodium,
      resulting in weight gains, increased pre-dialysis blood pressure, but less
      symptomatic intradialytic hypotension. Following readjustment of volumetric
      dialysate mixing, excess weight gains and increased blood pressure resolved over
      4 weeks, highlighting the importance of checking the delivered dialysate sodium
      following a change in dialysate acid concentrate.

PMID- 22865480
TI  - Multi-site pain and working conditions as predictors of work ability in a 4-year
      follow-up among food industry employees.
AB  - BACKGROUND: We investigated the separate and joint effects of multi-site
      musculoskeletal pain and physical and psychosocial exposures at work on future
      work ability. METHODS: A survey was conducted among employees of a Finnish food
      industry company in 2005 (n = 1201) and a follow-up survey in 2009 (n = 734).
      Information on self-assessed work ability (current work ability on a scale from 0
      to 10; 7 = poor work ability), multi-site musculoskeletal pain (pain in at least
      two anatomical areas of four), leisure-time physical activity, body mass index
      and physical and psychosocial exposures was obtained by questionnaire. The
      separate and joint effects of multi-site pain and work exposures on work ability
      at follow-up, among subjects with good work ability at baseline, were assessed by
      logistic regression, and p-values for the interaction derived. RESULTS: Compared
      with subjects with neither multi-site pain nor adverse work exposure, multi-site
      pain at baseline increased the risk of poor work ability at follow-up, allowing
      for age, gender, occupational class, body mass index and leisure-time physical
      activity. The separate effects of the work exposures on work ability were
      somewhat smaller than those of multi-site pain. Multi-site pain had an
      interactive effect with work environment and awkward postures, such that no
      association of multi-site pain with poor work ability was seen when work
      environment was poor or awkward postures present. CONCLUSIONS: The decline in
      work ability connected with multi-site pain was not increased by exposure to
      adverse physical or psychosocial factors at work.

PMID- 22865481
TI  - Multidetector computed tomography of chest trauma: indications, technique and
      interpretation.
AB  - BACKGROUND: Chest traumas are a significant cause of mortality and morbidity,
      especially in the younger population.Methods Diagnostic imaging plays a key role
      in their management. Multidetector computed tomography (MDCT) is the most
      important imaging method in this field. Its advantages include especially high
      speed and high geometric resolution in any plane.Results The method allows us to
      view large parts of the body with minimal motion artifacts and to create accurate
      multiplanar and three-dimensional (3D) reformations, which make the diagnosis
      significantly more accurate. Because of its advantages MDCT has become the first
      choice method in high-energy traumas.Conclusion This article summarises the
      position of MDCT in the diagnostic algorithm of chest injuries, technical aspects
      of the examination and imaging findings in traumas of the individual chest
      compartments. TEACHING POINTS: * Diagnostic imaging plays a key role in the
      management of high-energy chest trauma. * MDCT is the most important imaging
      method in this kind of injury, as detailed information can be acquired in a short
      acquisition time. * Multiplanar and three-dimensional (3D) reformattings make the
      diagnosis significantly more accurate.

PMID- 22865482
TI  - Ethical concepts and future challenges of neuroimaging: an Islamic perspective.
AB  - Neuroscience is advancing at a rapid pace, with new technologies and approaches
      that are creating ethical challenges not easily addressed by current ethical
      frameworks and guidelines. One fascinating technology is neuroimaging, especially
      functional Magnetic Resonance Imaging (fMRI). Although still in its infancy, fMRI
      is breaking new ground in neuroscience, potentially offering increased
      understanding of brain function. Different populations and faith traditions will
      likely have different reactions to these new technologies and the ethical
      challenges they bring with them. Muslims are approximately one-fifth of world
      population and they have a specific and highly regulated ethical and moral code,
      which helps them deal with scientific advances and decision making processes in
      an Islamically ethical manner. From this ethical perspective, in light of the
      relevant tenets of Islam, neuroimaging poses various challenges. The privacy of
      spirituality and the thought process, the requirement to put community interest
      before individual interest, and emphasis on conscious confession in legal
      situations are Islamic concepts that can pose a challenge for the use of
      something intrusive such as an fMRI. Muslim moral concepts such as There shall be
      no harm inflicted or reciprocated in Islam and Necessities overrule prohibitions
      are some of the criteria that might appropriately be used to guide advancing
      neuroscience. Neuroscientists should be particularly prudent and well prepared in
      implementing neuroscience advances that are breaking new scientific and ethical
      ground. Neuroscientists should also be prepared to assist in setting the ethical
      frameworks in place in advance of what might be perceived as runaway applications
      of technology.

PMID- 22865483
TI  - Responses of PTTH-producing neurosecretory neurons in Lymantria dispar
      caterpillars exposed to cadmium.
AB  - Lymantria dispar, as most invasive insect species, is very adaptable and reacts
      quickly to changing environment. Neuroendocrine system first reacts to stress in
      insects, and specific neurohormonal reorganization may be used in early heavy
      metal risk assessment. Prothoracicotropic neurohormones (PTTH) control
      ecdysteroid synthesis (morphogenetic and stress hormones) in insects. In this
      article, we report the presence of PTTH immunoreactive molecules in L2'
      dorsolateral neurosecretory neurons (nsn) in caterpillar brains and changes after
      exposure to pollutant stress of different intensity. For 3 days, after molting
      into the 4th instar, caterpillars of Lymantria dispar were fed with a high wheat
      germ diet without (control) or with added cadmium (experimental groups: 10, 30,
      100, 250 MUg Cd/g dry food weight). Changes in PTTH producing L2' nsn and
      differences in the intensity of protein bands in the region of PTTH molecular
      mass (Mr 11-15 kDa) were analyzed. The number of L2' neurons tended to decrease
      except in the group given the highest cadmium concentration (250 MUg). The
      neurons were enlarged after acute treatment especially in the group given the
      highest cadmium concentration. The size of L2' nsn nuclei was decreased only in
      the group fed with 30 MUg Cd. Protein band intensity in the Mr region of PTTH
      remained unchanged in all groups except for the group given the diet with the
      highest Cd concentration.

PMID- 22865484
TI  - Mixed-effects Gaussian process functional regression models with application to
      dose-response curve prediction.
AB  - We propose a new semiparametric model for functional regression analysis,
      combining a parametric mixed-effects model with a nonparametric Gaussian process
      regression model, namely a mixed-effects Gaussian process functional regression
      model. The parametric component can provide explanatory information between the
      response and the covariates, whereas the nonparametric component can add
      nonlinearity. We can model the mean and covariance structures simultaneously,
      combining the information borrowed from other subjects with the information
      collected from each individual subject. We apply the model to dose-response
      curves that describe changes in the responses of subjects for differing levels of
      the dose of a drug or agent and have a wide application in many areas. We
      illustrate the method for the management of renal anaemia. An individual dose
      response curve is improved when more information is included by this mechanism
      from the subject/patient over time, enabling a patient-specific treatment regime.

PMID- 22865485
TI  - Mapping the frontal sinus ostia using virtual endoscopy.
AB  - OBJECTIVES/HYPOTHESIS: To determine the relative location of the frontal sinus
      opening to other frontal cells using virtual endoscopy; and to assess whether the
      relative location of the frontal sinus ostium can be predicted. STUDY DESIGN:
      Retrospective analysis of high-resolution computed tomography scans from 50 adult
      patients without frontal sinus disease or previous sinus surgery. METHODS: Using
      virtual endoscopy software, 100 frontal recesses were mapped for the presence and
      relative position of the frontal sinus ostium to the following cells: agger nasi
      (ANC); frontal bullar; frontal types 1, 2, and 3; supraorbital ethmoid;
      suprabullar; and intersinus septal cells. RESULTS: ANC and frontal type 3 cells
      were present in 92% and 45% of frontal recesses, respectively. All other cell
      types had a prevalence of <= 25%. Fifty percent of recesses had two rows of ostia
      anterior to posterior (AP), and the frontal opening was anterior in 52%. When
      there were three rows of cells AP (39%), the frontal opening was in the center in
      64% of cases. Thirty-five percent of recesses had two rows of ostia medial to
      lateral (ML), and the frontal opening was medial 80% of the time. When there were
      three rows of openings ML (45%), the frontal opening was in the center 56% of the
      time. CONCLUSIONS: The frontal sinus recess is variable and complex. Virtual
      endoscopy can be used to analyze the frontal recess and assist in presurgical
      planning. Although there is variability in the ostial configuration present in
      the frontal recess, the probable position of the frontal sinus ostium can be
      predicted.

PMID- 22865486
TI  - Interaction among nitric oxide (NO)-related genes in migraine susceptibility.
AB  - The pathogenic mechanisms involved in migraine are complex and not completely
      clarified. Because there is evidence for the involvement of nitric oxide (NO) in
      migraine pathophysiology, candidate gene approaches focusing on genes affecting
      the endothelial function have been studied including the genes encoding
      endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and vascular
      endothelial growth factor (VEGF). However, investigations on gene-gene
      interactions are warranted to better elucidate the genetic basis of migraine.
      This study aimed at characterizing interactions among nine clinically relevant
      polymorphisms in eNOS (T(-786)C/rs2070744, the 27 bp VNTR in intron 4, the
      Glu298Asp/rs1799983, and two additional tagSNPs rs3918226 and rs743506), iNOS (C(
      1026)A/rs2779249 and G2087A/rs2297518), and VEGF (C(-2578)A/rs699947 and G(
      634)C/rs2010963) in migraine patients and control group. Genotypes were
      determined by real-time polymerase chain reaction using the Taqman((r)) allele
      discrimination assays or PCR and fragment separation by electrophoresis in 99
      healthy women without migraine (control group) and in 150 women with migraine
      divided into two groups: 107 with migraine without aura and 43 with aura. The
      multifactor dimensionality reduction method was used to detect and characterize
      gene-gene interactions. We found a significant interaction between eNOS rs743506
      and iNOS 2087G/A polymorphisms in migraine patients compared to control group (P
      < 0.05), suggesting that this combination affect the susceptibility to migraine.
      Further studies are needed to determine the molecular mechanisms explaining this
      interaction.

PMID- 22865487
TI  - 18beta-glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in
      human epithelial ovarian carcinoma cells via activation of death receptor and
      mitochondrial pathway.
AB  - The Hsp90 inhibition has been shown to induce apoptosis in various cancer cells.
      The licorice compounds may enhance the anti-cancer drug effect. However, effect
      of the licorice compounds on the Hsp90 inhibition-induced apoptosis in ovarian
      cancer cells has not been studied. To assess the ability of 18beta-glycyrrhetinic
      acid to promote apoptosis, we examined whether 18beta-glycyrrhetinic acid
      potentiated the Hsp90 inhibitor-induced apoptosis in the human epithelial ovarian
      carcinoma cell lines OVCAR-3 and SK-OV-3. Radicicol and geldanamycin induced a
      decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, an increase in Bax
      levels, the mitochondrial transmembrane potential loss, cytochrome c release,
      activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in
      the tumor suppressor p53 levels. 18beta-Glycyrrhetinic acid enhanced Hsp90
      inhibitor-induced apoptosis-related protein activation, nuclear damage, and cell
      death. The results suggest that 18beta-glycyrrhetinic acid may potentiate the
      Hsp90 inhibition-induced apoptosis in ovarian carcinoma cell lines via the
      activation of the caspase-8- and Bid-dependent pathways and the mitochondria
      mediated cell death pathway, leading to activation of caspases. Combination of
      Hsp90 inhibitors and 18beta-glycyrrhetinic acid may confer a benefit in the
      treatment of epithelial ovarian adenocarcinoma.

PMID- 22865488
TI  - The antinociceptive effects of systemic administration of tramadol, gabapentin
      and their combination on mice model of acute pain.
AB  - OBJECTIVES: The aim of the present study was to investigate the possible
      antinociceptive effects of systemic administration of tramadol and gabapentin
      either alone or in combination on acute pain models in mice. METHODS: After
      obtaining the approval of Animal Ethics Committee; 96 BALB/c albino male mice
      were divided into 12 groups: (I) control without injection, (II) control treated
      with saline, (III)-(IV) mice treated with tramadol 10 mg/kg or 30 mg/kg, (V)
      (VIII) mice treated with gabapentin; 30, 100, 200, 300 mg/kg respectively. In
      order to determine possible interactions between tramadol gabapentin and; mice
      received four different combinations of tramadol + gabapentin (30+30, 30+100,
      30+200 and 30+300 mg/kg) (Groups IX-XII respectively). Mice received 0.1 ml
      solution for every 10 g of their weight. The drug was injected into peritonea.
      Thirty minutes after the drug injection, tail-flick and hot-plate tests were
      conducted. RESULTS: Ten and 30 mg/kg tramadol produced dose dependent
      antinociceptive effect in tail-flick and hot plate tests. Gabapentin had no
      antinociceptive effect in the tail flick test except 300 mg/kg dose, and had dose
      dependent antinociceptive effect in hot-plate test. In both tests, various
      combinations of tramadol and gabapentin produced an antinociceptive effect that
      is greater than that produced by tramadol and gabapentin alone. But, just 30
      mg/kg tramadol + 300 mg/kg gabapentin combination caused statistically
      significant increase in both tests (p<0.05). CONCLUSION: When gabapentin and
      tramadol were used in combination, gabapentin had no additive antinociceptive
      effect except for 300 mg/kg in tail-flick and hot-plate tests. Tail-flick test
      showed that tramadol produced better antinociceptive effect than gabapentin.

PMID- 22865489
TI  - Intraperitoneal ropivacaine or ropivacaine plus meperidine for laparoscopic
      gynecological procedures.
AB  - OBJECTIVES: Postoperative pain after laparoscopic surgery is less intense than
      after laparotomy and patients may benefit from an intraperitoneal injection of
      local anesthetic and opioids. We aimed to compare intraperitoneal 0.75%
      ropivacaine with 0.75% ropivacaine plus meperidine for postoperative analgesia in
      patients undergoing gynecologic laparoscopy. METHODS: At the end of gynecologic
      laparoscopy, in a double-blind, randomized manner, one of the following
      injections was given intraperitoneally. Patients were allocated into three
      groups: Patients in R Group (n=18) were given 0.75% ropivacaine 3 mg/kg in 200 mL
      saline; patients in RM Group (n=17) were given meperidine 50 mg plus 0.75%
      ropivacaine 3 mg/kg in 200 mL saline; patients in C Group (n=18) were given 200
      mL saline through the trocars. All patients were given diclofenac sodium when
      they had pain (VAS 3) and 1 mg/kg meperidine i.v. was also given when pain
      persisted. RESULTS: The pain scores and analgesic requirements during the first
      postoperative hour were significantly lower in the RM Group than those in the R
      and C Groups. Beyond that time, the pain scores were similar in all groups and
      there were no differences in total analgesic requirement in 24 h between groups.
      The three groups were comparable for shoulder pain and side effects. CONCLUSION:
      The intraperitoneal infiltration of 0.75% ropivacaine plus meperidine reduced
      pain scores and analgesic requirement during the first one hour after gynecologic
      laparoscopy compared with the intraperitoneal infiltration of ropivacaine or
      saline.

PMID- 22865490
TI  - The efficacy of adding dexketoprofen trometamol to tramadol with patient
      controlled analgesia technique in post-laparoscopic cholecystectomy pain
      treatment.
AB  - OBJECTIVES: Pain treatment in laparoscopic cholecystectomy, which is performed in
      increasing numbers as an ambulatory procedure, is an important issue.Although
      laparoscopic cholecystectomy is regarded as an ambulatory procedure, patients are
      often hospitalized due to pain and this increases opioid consumption and side
      effects caused by opioids. This study aims at evaluating the efficacy of adding
      dexketoprofen trometamol to tramadol with patient controlled analgesia (PCA) in
      postlaparoscopic cholecystectomy pain treatment. METHODS: 40 patients in ASA I-II
      risk groups aged between 18-65 years were enrolled in the study and were
      randomized using closed envelope method. In Group TD 600 mg tramadol and 100 mg
      dexketoprofen trometamol, in Group T 600 mg tramadol was added to 100 ml 0.9%
      normal saline for PCA. 8 mg lornoxicam iv was given if VAS >40 in the
      postoperative period. RESULTS: There was no statistically significant difference
      in terms of adverse effects (hypotension, bradycardia, sedation) but in Group T 4
      patients complained of nausea and 3 complained of vomiting. Opioid consumption
      was lower and patient satisfaction was higher in group TD. CONCLUSION: This study
      has shown that adding dexketoprofen trometamol to tramadol in patient controlled
      analgesia following laparoscopic cholecystectomy lowers VAS scores, increases
      patient satisfaction and decreases opioid consumption.

PMID- 22865491
TI  - [Women's approach to childhood toothache, abdominal ache and earache].
AB  - OBJECTIVES: This study was conducted to determine women's about attitudes child's
      teeth, abdomen and ear ache. METHODS: Those who had lived in Antalya that 6
      number primary health care center between March-May 2004 were enrolled in the
      study. As data collecting tools. A questionnaire prepared by the authors. This
      study was determined that 29.2 % of the mothers carried out mixture who had
      prepared at home to child's abdomen and foot base; 30.3 % were to put breast milk
      childs' ear; 38.9 % were placed aspirin, salt and salts of lemon to childs' teeth
      ache. RESULTS: The majority of the women make a wrong practices child that teeth,
      abdomen and ear ache. This traditional practice effecting factors were the
      women's educational status and age. CONCLUSION: The results of the study that
      education about child care, common health problems and incorrect applications
      shoud be given to women by nurse.

PMID- 22865492
TI  - [Efficacy of transforaminal lumbar epidural steroid injections in patients with
      lumbar radiculopathy].
AB  - OBJECTIVES: This study looks into the efficacy and safety of the transforaminal
      lumbar epidural steroid injection (TLESI) applied to patients with radiculopathy
      due to lumbar disk herniation. METHODS: The patients' files which were applied
      TLESI, were retrospectively scanned. Patients who did not respond to one-month
      conservative treatment and who were detected to have bulging or protruding lumbar
      disk herniation as a result of imaging methods were included in the study. All
      applications were performed with C-arm fluoroscopy under local anesthesia by
      outpatient method. In all cases, a mix of 80 mg triamsinolone and 0.25%
      bupivacaine, was transforaminally injected to the anterior epidural area. Initial
      VAS pain scores were compared with the values of the 1, 3 and 6th months after
      the application. Patient satisfaction was determined through scoring.
      Furthermore, early and late term complications were collected for evaluation.
      RESULTS: A total of 222 patients were administered TLESI 460 times (average: 2.1,
      repeat interval: 1-6 times). The applications were carried out most frequently at
      the levels of L4-L5 and L5-S1. While the initial VAS score average was 8.2+/-0.7,
      after TLESI, it was 5.0+/-1.6, 4.8+/-1.5 and 5.1+/-1.5 in the 1, 3 and 6th
      months, respectively. 63.9% of the patients (n=142) defined the treatment as
      'good and excellent'. No major complications were experienced and the overall
      minor complication rate was 11.1%. CONCLUSION: It was seen that TLESI was an
      efficient and safe method in the short and medium term.

PMID- 22865493
TI  - Comparison of blunt and sharp needles for transforaminal epidural steroid
      injections.
AB  - OBJECTIVES: The aim of this study was to compare the sharp and blunt needles in
      order to determine the incidence of complications during transforaminal anterior
      epidural steroid injections. METHODS: In this retrospective study, 185 cases that
      undergo transforaminal epidural steroid injection with sharp or blunt needles
      were evaluated between June 2004 and December 2008. Patients age, sex, diagnosis,
      needle type (sharp or blunt), volume of local anesthetic and steroid injected,
      complications (paresthesia, dural puncture, bleeding, paralysis, intravascular
      penetration, headache, local back pain, temporary motor loss in lower
      extremities) was recorded. RESULTS: 3 cases in blunt needle group and 8 cases in
      sharp needle group showed paresthesia during the procedure. The difference was
      not found to be significant among the groups. Vascular penetration was observed
      in 2 cases in blunt and 13 cases in sharp needle group and the difference between
      groups was statistically significant (p<0.001). Dural puncture and headache
      incidence were not significant when the two groups are compared. The local back
      pain at the injection site had a higher incidence in the blunt needle group.
      CONCLUSION: When using the blunt needles, vascular penetration and paresthesia
      were less during transforaminal epidural steroid injections. Therefore blunt
      needles seem to be more advantageous.

PMID- 22865494
TI  - [Ultrasound guided multiple peripheral nerve blocks in a high-risk patient].
AB  - Using low doses of local anesthetic, ultrasound guided multiple nerve blocks were
      performed in a high-risk patient. Surgical anesthesia was provided in an ASA III
      classified patient who received ultrasound guided right femoral and bilateral
      popliteal blocks. Using 80 mm needle, blocks were performed using a mixture of 10
      ml 0.5% levobupivacaine and lidocaine 2%. Femoral nerve block was performed using
      10 ml of levobupivacaine 0.5%. Visualization of nerves by ultrasound guidance
      increases block success rate and contributes to lower local anesthetic doses.
      Using lower doses of local anesthetic during ultrasound-guided blocks allows
      multiple blocks to be performed safely.

PMID- 22865495
TI  - Musculocutaneous neuropathy after anaesthesia for thyroid surgery: a case report.
AB  - Postoperative isolated injury of the musculocutaneous nerve is a rare disorder
      and complication. Reported cases are claimed to present with loss of biceps and
      brachialis power without neuropathic pain. When injury occurs to one of the
      terminal branches of the brachial plexus, the lateral cutaneous nerve of the
      forearm, pain is the major symptom and it typically radiates along the radial
      aspect of the forearm. In the literature, isolated lesions of the
      musculocutaneous nerve have been attributed to repeated microtrauma, indirect
      trauma or direct trauma to the nerve. It may also occur due to strenuous
      extension of the forearm for prolonged periods.

PMID- 22865496
TI  - Electrolysis of water and common salt solutions.

PMID- 22865497
TI  - Antimicrobial use in the ICU: indications and accuracy--an observational trial.
AB  - BACKGROUND: In intensive care unit (ICU) patients, signs of infection and
      inflammation are similar, making diagnosis of bacterial infections difficult.
      Antimicrobials may therefore be overused, contributing to development of
      antimicrobial-resistant bacteria. OBJECTIVES: To measure the accuracy of
      clinician decisions to start antimicrobials; to correlate clinician certainty
      with the presence of infection; and to examine whether physiological variables
      correlate with clinician certainty. DESIGN: Prospective observational study.
      SETTING AND PATIENTS: Patients staying >48 hours in a general ICU of a tertiary
      care hospital. MEASUREMENTS: The ICU clinician's certainty for the presence of
      infection was recorded when starting antimicrobials. An independent infectious
      diseases (ID) specialist determined if antimicrobials were required and if
      infection was present. Clinician antibiotic start decisions were tested for
      accuracy according to the ID determination for the presence of infection.
      RESULTS: Empirical antimicrobial therapy was justified by the presence of
      infection on 67/125 (54%) occasions. Clinician certainty for infection correlated
      well with the presence of defined infection (r(2) = 0.78), however, infection was
      defined on 6/19 (31%) occasions when ICU clinician certainty was low (<=2), and
      antimicrobials were prescribed even when clinician certainty was minimal.
      Antimicrobial course length was similar whether infection was defined or not
      (11.5 +/- 9.2 vs 10.7 +/- 9.1 days; P = 0.65). Physiological variables were not
      associated with clinician certainty of infection. CONCLUSIONS: Antimicrobial
      therapy is probably overused in the ICU, possibly resulting from difficulties in
      diagnosis and the perceived greater risk of untreated infection when compared to
      the risks of potentially unnecessary antimicrobial therapy. Efforts to improve
      antimicrobial-related decision-making should be mandatory.

PMID- 22865498
TI  - Effects of marine-derived omega-3 fatty acids on systemic hemodynamics at rest
      and during stress: a dose-response study.
AB  - BACKGROUND: Omega-3 fatty acids reduced heart rate (HR) and blood pressure (BP)
      in some studies, but dose-response studies are rare, and little is known about
      underlying mechanisms. PURPOSE: We examined effects of 0.85 g/day
      eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (low dose) and 3.4 g/day
      EPA + DHA (high dose) on HR and systemic hemodynamics during rest, speech, and
      foot cold pressor tasks. METHODS: This was a dose-response, placebo-controlled,
      double-blind, randomized, crossover trial (8-week treatment, 6-week washout) in
      26 adults. RESULTS: Throughout the testing sessions, HR was reduced in a dose
      dependent manner. The high dose reduced BP and stroke volume and increased pre
      ejection period. Reductions in BP were associated with increases in erythrocyte
      omega-3 fatty acids. CONCLUSIONS: High-dose long-chain omega-3 fatty acids can
      reduce BP and HR, at rest and during stress. These findings suggest that at-risk
      populations may achieve benefits with increased omega-3 intake. The trial was
      registered on ClinicalTrials.gov (NCT00504309).

PMID- 22865499
TI  - Life 1 year after a quit attempt: real-time reports of quitters and continuing
      smokers.
AB  - BACKGROUND: Smokers are often reluctant to quit because they fear long-lasting
      withdrawal. Yet little research prospectively examines smokers' withdrawal longer
      than 1 month post-quit. PURPOSE: The aim of this study was to compare successful
      versus unsuccessful quitters' withdrawal, positive affect/pleasure, and lifestyle
      at 1 year post-quit. METHODS: Smokers (N = 572) in a cessation trial completed
      ecological momentary assessments four times a day for 1 week pre-quit, 1 week
      post-quit, and 1 week at 1 year post-quit. RESULTS: From pre-quit to 1 year
      later, only quitters reported sizeable declines in craving and restlessness, and
      fewer stressful events. At 1 year, quitters, on average, reported no significant
      craving. Continuing smokers reduced their cigarette consumption considerably from
      pre-quit to 1 year later. CONCLUSIONS: Contrary to smokers' worries, long-term
      quitters reported less craving and restlessness than when they smoked (perhaps
      because cessation eliminates the acute nicotine withdrawal smokers experience
      between cigarettes). This information may encourage smokers to quit and endure
      withdrawal.

PMID- 22865500
TI  - cis- and trans-acting localization determinants of pH response regulator Rim13 in
      Saccharomyces cerevisiae.
AB  - The Rim101/PacC pathway governs adaptation to alkaline pH in many fungi. Output
      of the pathway is mediated by transcription factors of the Rim101/PacC family,
      which are activated by proteolytic cleavage. The proteolytic complex includes
      scaffold protein Rim20 and endosome-associated subunits of the endosomal sorting
      complex required for transport (ESCRT). We provide here evidence that
      Saccharomyces cerevisiae Rim13, the protease that is implicated in Rim101
      cleavage, is associated with the Rim20-ESCRT complex, and we investigate its
      regulation. Rim13-GFP is dispersed in cells grown in acidic medium but forms
      punctate foci when cells encounter alkaline conditions. A vps4Delta mutant, which
      accumulates elevated levels of endosomal ESCRT, also accumulates elevated levels
      of Rim13-GFP foci, independently of external pH. In the vps4Delta background,
      mutation of ESCRT subunit Snf7 or of Rim20 blocks the formation of Rim13 foci,
      and we found that Rim13 and Rim20 are colocalized. The Rim13 ortholog PalB of
      Aspergillus nidulans has been shown to undergo ESCRT and membrane association
      through an N-terminal MIT domain, but Rim13 orthologs in the Saccharomyces clade
      lack homology to this N-terminal region. Instead, there is a clade-limited C
      terminal region, and we show that point mutations in this region prevent punctate
      localization and impair Rim13 function. We suggest that RIM13 arose from its
      ancestral gene through two genome rearrangements. The ancestor lost the coding
      region for its MIT domain through a 5' rearrangement and acquired the coding
      region for the Saccharomyces-specific functional equivalent through a 3'
      rearrangement.

PMID- 22865502
TI  - New multifunctional porous materials based on inorganic-organic hybrid single
      walled carbon nanotubes: gas storage and high-sensitive detection of pesticides.
AB  - Single-walled carbon nanotubes (SWNTs) that are covalently functionalized with
      benzoic acid (SWNT-PhCOOH) can be integrated with transition-metal ions to form
      3D porous inorganic-organic hybrid frameworks (SWNT-Zn). In particular, N(2)
      adsorption analysis shows that the BET surface area increases notably from 645.3
      to 1209.9 m(2)  g(-1) for SWNTs and SWNT-Zn, respectively. This remarkable
      enhancement in the surface area of SWNT-Zn is presumably due to the microporous
      motifs from benzoates coordinated to intercalated zinc ions between the
      functionalized SWNTs; this assignment was also corroborated by NLDFT pore-size
      distributions. In addition, the excess-H(2)-uptake maximum of SWNT-Zn reaches
      about 3.1 wt. % (12 bar, 77 K), which is almost three times that of the original
      SWNTs (1.2 wt. % at 12 bar, 77 K). Owing to its inherent conductivity and pore
      structure, as well as good dispersibility, SWNT-Zn is an effective candidate as a
      sensitive electrochemical stripping voltammetric sensor for organophosphate
      pesticides (OPs): By using solid-phase extraction (SPE) with SWNT-Zn-modified
      glassy carbon electrode, the detection limit of methyl parathion (MP) is 2.3 ng
      mL(-1).

PMID- 22865501
TI  - Regulation of the cell division cycle in Trypanosoma brucei.
AB  - The cell division cycle is tightly regulated by the activation and inactivation
      of a series of proteins that control the replication and segregation of
      organelles to the daughter cells. During the past decade, we have witnessed
      significant advances in our understanding of the cell cycle in Trypanosoma brucei
      and how the cycle is regulated by various regulatory proteins. However, many
      other regulators, especially those unique to trypanosomes, remain to be
      identified, and we are just beginning to delineate the signaling pathways that
      drive the transitions through different cell cycle stages, such as the G(1)/S
      transition, G(2)/M transition, and mitosis-cytokinesis transition. Trypanosomes
      appear to employ both evolutionarily conserved and trypanosome-specific molecules
      to regulate the various stages of its cell cycle, including DNA replication
      initiation, spindle assembly, chromosome segregation, and cytokinesis initiation
      and completion. Strikingly, trypanosomes lack some crucial regulators that are
      well conserved across evolution, such as Cdc6 and Cdt1, which are involved in DNA
      replication licensing, the spindle motor kinesin-5, which is required for spindle
      assembly, the central spindlin complex, which has been implicated in cytokinesis
      initiation, and the actomyosin contractile ring, which is located at the cleavage
      furrow. Conversely, trypanosomes possess certain regulators, such as cyclins,
      cyclin-dependent kinases, and mitotic centromere-associated kinesins, that are
      greatly expanded and likely play diverse cellular functions. Overall,
      trypanosomes apparently have integrated unique regulators into the evolutionarily
      conserved pathways to compensate for the absence of those conserved molecules
      and, additionally, have evolved certain cell cycle regulatory pathways that are
      either different from its human host or distinct between its own life cycle
      forms.

PMID- 22865504
TI  - Immunolocalization, gene expression, and enzymatic activity of cyclooxygenases,
      prostaglandin e2-9-ketoreductase, and nitric oxide synthases in Mediterranean
      buffalo (Bubalus bubalis) corpora lutea during diestrus.
AB  - Immunopresence, gene expression, and enzymatic activity of cyclooxygenase 1
      (COX1), COX2, PGE2-9-ketoreductase (PGE2-9-K), endothelial (eNOS), and inducible
      nitric oxide synthases (iNOS), and hormone in vitro production were examined in
      early, mid, late, and regressive buffalo corpora lutea (CL). COX1 immunosignals
      were detected in the cytoplasm of small luteal cells, COX2 in large luteal cells,
      and PGE2-9-K in all luteal cells. COX2 and PGE2-9-K immunosignals were greater in
      late CL. Immunopresence of both NOS types were evidenced in the nuclei and
      cytoplasm of all luteal cells, as well as in the nuclei of endothelial cells,
      during all stages studied. The eNOS and iNOS immunosignals increased during the
      early stage. COX1 transcripts were lower in late and regressive CL, COX2 in late,
      PGE2-9-K higher in regressive, and iNOS higher in early and lower in regressive
      CL. COX1 enzymatic activity was lower in regressive CL, COX2 increased in mid and
      late stages, and PGE2-9-K was higher in late CL. Endothelial NOS activity was
      higher during mid and late stages and lower in regressive, whereas iNOS was
      greater in late and lower in early. Progesterone in vitro release was higher in
      mid and lower in late phase, while PGF2alpha synthesis was higher in late CL and
      lower in regressive, and PGE2 was higher during regressive stage. These results
      support the idea that COX, NOS, and PGE2-9-K regulate buffalo CL life span. In
      particular, regressive CL seems involved in the development of the contralateral
      early CL, through the production of the luteotrophic PGE2.

PMID- 22865503
TI  - Addition of perfluorocarbons to alginate hydrogels significantly impacts
      molecular transport and fracture stress.
AB  - Perfluorocarbons (PFCs) are used in biomaterial formulations to increase oxygen
      (O(2) ) tension and create a homogeneous O(2) environment in three-dimensional
      tissue constructs. It is unclear how PFCs affect mechanical and transport
      properties of the scaffold, which are critical for robustness, intracellular
      signaling, protein transport, and overall device efficacy. In this study, we
      investigate composite alginate hydrogels containing a perfluorooctyl bromide
      (PFOB) emulsion stabilized with Pluronic((r)) F68 (F68). We demonstrate that PFC
      addition significantly affects biomaterial properties and performance. Solution
      and hydrogel mechanical properties and transport of representative hydrophilic
      (riboflavin), hydrophobic (methyl and ethyl paraben), and protein (bovine serum
      albumin, BSA) solutes were compared in alginate/F68 composite hydrogels with or
      without PFOB. Our results indicate that mechanical properties of the
      alginate/F68/PFOB hydrogels are not significantly affected under small strains,
      but a significant decrease fracture stress is observed. The effective diffusivity
      D(eff) of hydrophobic small molecules decreases with PFOB emulsion addition, yet
      the D(eff) of hydrophilic small molecules remained unaffected. For BSA, the
      D(eff) increased and the loading capacity decreased with PFOB emulsion addition.
      Thus, a trade-off between the desired increased O(2) supply provided by PFCs and
      the mechanical weakening and change in transport of cellular signals must be
      carefully considered in the design of biomaterials containing PFCs.

PMID- 22865505
TI  - Voiding dysfunction related to a vaginal hematoma after a PerigeeTM procedure.

PMID- 22865506
TI  - Experience with microarray-based comparative genomic hybridization for prenatal
      diagnosis in over 5000 pregnancies.
AB  - OBJECTIVE: To demonstrate the usefulness of microarray testing in prenatal
      diagnosis based on our laboratory experience. METHODS: Prenatal samples received
      from 2004 to 2011 for a variety of indications (n = 5003) were tested using
      comparative genomic hybridization-based microarrays targeted to known chromosomal
      syndromes with later versions of the microarrays providing backbone coverage of
      the entire genome. RESULTS: The overall detection rate of clinically significant
      copy number alterations (CNAs) among unbiased, nondemise cases was 5.3%.
      Detection rates were 6.5% and 8.2% for cases referred with abnormal ultrasounds
      and fetal demise, respectively. The overall rate of findings with unclear
      clinical significance was 4.2% but would reduce to 0.39% if only de novo CNAs
      were considered. In cases with known chromosomal rearrangements in the fetus or
      parent, 41.1% showed CNAs related to the rearrangements, whereas 1.3% showed
      clinically significant CNAs unrelated to the karyotype. Finally, 71% of the
      clinically significant CNAs found by microarray were below the resolution of
      conventional karyotyping of fetal chromosomes. CONCLUSIONS: Microarray analysis
      has advantages over conventional cytogenetics, including the ability to more
      precisely characterize CNAs associated with abnormal karyotypes. Moreover, a
      significant proportion of cases studied by array will show a clinically
      significant CNA even with apparently normal karyotypes.

PMID- 22865507
TI  - Endolymphatic hydrops in the horizontal semicircular canal: a morphologic
      correlate for canal paresis in Meniere's disease.

PMID- 22865509
TI  - A technical note for improving animal welfare and model validity in the chronic
      constriction injury model of neuropathic pain.

PMID- 22865508
TI  - Inverse pattern of photoreceptor abnormalities in retinitis pigmentosa and cone
      rod dystrophy.
AB  - PURPOSE: To determine the characteristics of the photoreceptor abnormalities in
      retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). METHODS: We evaluated the
      photoreceptor abnormalities using spectral-domain optical coherence tomography
      (SD-OCT) in 28 patients with RP and 17 patients with CRD. The OCT images and full
      field electroretinograms were obtained from 21 eyes in normal subjects who were
      age-matched to patients with RP and CRD and served as controls. RESULTS: Eyes
      with RP and CRD had markedly decreased rod responses (6.5 and 57.5 % of normal
      value), maximal responses (9.6 and 51.6 %), cone (16.5 and 25.8 %), and 30-Hz
      flicker responses (17.8 and 30.1 % of normal value), and their P values were
      smaller than 0.0003. On comparison of ERG data between RP and CRD, they had
      statistically significant differences in rod responses (P < 0.0003) and maximal
      responses (P < 0.0003). However, there were no statistical differences in cone
      response and a weak difference in 30-Hz flicker responses (P < 0.017). The best
      corrected visual acuity was -0.03 +/- 0.09 (logMAR, mean +/- standard deviation
      [SD]) in eyes with RP, but 0.57 +/- 0.54 in eyes with CRD. SD-OCT showed that
      eyes with RP had an intact reflective line at the junction between the
      photoreceptor inner and outer segment (IS/OS) at the fovea, while eyes with CRD
      had no IS/OS. The extent of the central visual field was correlated with the
      IS/OS length at the macula in eyes with RP. CONCLUSION: The distribution patterns
      of the IS/OS line help to differentiate between RP and CRD.

PMID- 22865510
TI  - Changing trends in a decade of vascular radiology-the impact of technical
      developments of non-invasive techniques on vascular imaging.
AB  - OBJECTIVES: This review aims to establish the impact on conventional angiography
      and endovascular intervention of contrast-enhanced magnetic resonance angiography
      (CE-MRA) and contrast-enhanced computed tomography angiography (CE-CTA) on a
      background of evolving technology, changing clinical requirements and resulting
      clinical repercussions. METHODS: The angiographic and interventional caseload was
      prospectively recorded between 1997 and 2010, along with the CE-MRA and CE-CTA
      caseload. Waiting times and the marginal cost analyses for 2001 and 2009 were
      also prospectively established. RESULTS: Conventional diagnostic angiographies
      declined from a peak of 847 to 121 per year while endovascular interventions
      continue in similar numbers. CE-MRA increased from effectively none initially to
      620 per year while CE-CTA has currently risen to 396 per year. Total diagnostic
      study numbers have increased but at reduced cost. Various influences are clear,
      including on-site modality availability, capability and accuracy along with
      impact of new therapies, research studies and adverse events. CONCLUSIONS:
      Vascular imaging has undergone a metamorphosis in little over a decade because of
      CE-MRA and CE-CTA. With waiting times significantly reduced since the start of
      the study and the cost-effectiveness of both CE-MRA and CE-CTA as primary
      diagnostic investigations established, further development of these services is
      inevitable. MAIN MESSAGES: * The availability of CE-MRA and CE-CTA has reduced
      the need for conventional angiography. * Both waiting times and the marginal cost
      analyses for CE-MRA and CE-CTA have reduced. * The impact of new therapies,
      research studies (e.g. ASTRAL) and adverse events is illustrated.

PMID- 22865511
TI  - Haunted by the ghost in the machine. Commentary on "The spirituality of human
      consciousness: a Catholic evaluation of some current neuro-scientific
      interpretations".
AB  - Metaphysical and epistemological dualism informs much contemporary discussion of
      the relationships of science and religion, in particular in relation to the
      neurosciences and the religious understanding of the human person. This dualism
      is a foundational artifact of modern culture; however, contemporary scientific
      research and historical theological scholarship encourage a more holistic view
      wherein human personhood is most fittingly understood as an emergent phenomenon
      of, but not simply reducible to, evolutionary and developmental neurobiology.

PMID- 22865512
TI  - Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis.
AB  - It has been 50 years since the first patients with tardive dyskinesia (TD) were
      described, but the pathophysiology is only partially understood and effective
      treatments have remained elusive. Newer atypical antipsychotics with less
      nonspecific activity at dopamine receptors have not heralded the end of tardive
      dyskinesia and merely highlight the incomplete understanding of the disorder. We
      present an overview of the existing pathophysiology of the disorder and
      incorporate recent developments in genetics and the study of human synaptic
      plasticity in other hyperkinetic movement disorders. We propose a hypothesis that
      dopamine-receptor sensitization and altered function of the N-methyl-D-aspartate
      receptor produces maladaptive synaptic plasticity, which allows the encoding of
      abnormal motor programs, and propose studies that would falsify or support this
      hypothesis. In conclusion, a maladaptive synaptic plasticity" hypothesis goes
      some way toward filling in the gaps of existing theories of TD with the
      pathophysiology of other hyperkinetic movement disorders. (c) 2012 Movement
      Disorder Society.

PMID- 22865513
TI  - Endoscopic sandwich technique for moderate nasal septal perforations.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this article was to describe our surgical
      technique for the treatment of nasal septal perforations with diameters of 1 to 2
      cm. STUDY DESIGN: Retrospective clinical research. METHODS: We reviewed 13
      patients with moderate nasal septal perforations (1-2 cm diameter) treated with a
      sandwich technique (bone or cartilage and quadriceps fascia graft as an
      interposition graft) by an endoscope-assisted intranasal approach from January
      2008 to June 2011. Follow-up periods were 3 months. RESULTS: Thirteen patients
      were treated with the sandwich technique. Twelve cases (92.3%) were completely
      healed. One case received incomplete closures without any postoperative symptoms.
      All patients were found not to have any complications after surgery. CONCLUSIONS:
      The transnasal endoscopic sandwich technique for repairing moderate nasal septal
      perforation (1-2 cm) has a high success rate and is easy to perform.

PMID- 22865514
TI  - Downregulation of nuclear respiratory factor-1 contributes to mitochondrial
      events induced by benzo(a)pyrene.
AB  - Environmental carcinogen benzo(a)pyrene (BaP) has been shown to be a genotoxicant
      that affects both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Nuclear
      respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that
      encode a range of mitochondrial proteins including mitochondrial transcription
      factor A (mtTFA). However, the role of NRF-1 in BaP-induced mitochondrial event
      is not clear. We investigated the change of NRF-1 and mtTFA in human bronchial
      epithelial cells (16HBE) elicited by BaP. The results indicated that BaP induced
      cell apoptosis, total mitochondrial enzymes activities and ATP levels decrease in
      dose- and time-dependent manners, respectively. The transcription and protein
      levels of NRF-1 and mtTFA decreased at 48 h after 16 MUM BaP treatment. Our
      results indicated downregulation of NRF-1 and mtTFA is involved in BaP-induced
      mitochondrial events.

PMID- 22865515
TI  - Evidence based rehabilitation in chronic pain syndromes.
AB  - Chronic pain syndrome (CPS) is a complex condition that presents a major
      challenge to physicians because of its unknown etiology and poor response to all
      kinds of therapies. It has been suggested that chronicity should be considered
      when pain persists longer than the acceptable healing time. The impact of chronic
      pain on patients' lives varies from minor limitations to complete loss of
      independence. The rehabilitation in CPSs is multi-disciplinary and involves
      physical, occupational, and manual therapy, aquatherapy, cognitive/behavioral
      therapy, biofeedback, psychotherapy, and some new therapies. In recent years, the
      point of view in chronic pain management has changed substantially and CPS is
      managed best with a multidisciplinary approach, including a rehabilitative
      process. The treatment protocol should be planned and modified individually. A
      combination of several methods has been tried, but long-term evidence-based
      studies are needed for new treatment modalities.

PMID- 22865516
TI  - [Our percutaneous vertebroplasty applications in vertebral compression
      fractures].
AB  - OBJECTIVES: We aimed to investigate the effectiveness and complications of the
      percutaneous vertebroplasty (PVP) applications in vertebral compression
      fractures. METHODS: Our study was carried out as a retrospective study in which
      PVP was conducted on patients with vertebral compression fractures due to benign
      or malignant causes between October 2006 and December 2009. The patients' pain
      was evaluated on a visual analog scale (VAS). In addition, the amount of cement
      injected, whether or not any leakage from the vertebrae corpus was seen, and any
      complications resulting from the application during or after the operation were
      recorded. The age and gender of the patients, duration of pain, number and
      location of fractured vertebrae, and the duration of follow-up were also
      collected for evaluation. RESULTS: A total of 15 patients were included in the
      assessment. Of the patients, 13 were female, and the mean age was 69.5+/-8.5
      years. A total of 19 PVPs were applied to the 15 patients. While initial VAS
      scores were 7.9+/-1.6, at the end of an average of 10.3+/-3.8 (range: 4-18)
      months of follow-up, VAS scores had fallen to 2.6+/-2.7. 80% of the patients
      reported at least a 50% reduction in pain scores compared to initial scores, and
      86.7% of them reported at least a 2-point decrease in VAS scores. In three
      patients, leakage of cement into the intervertebral disc occurred. CONCLUSION:
      PVP may be used successfully in symptomatic vertebral compression fractures not
      responding to medical treatment, with a low rate of complications.

PMID- 22865517
TI  - [Comparison of transdermal fentanyl for the management of cancer pain in adults
      and elders].
AB  - OBJECTIVES: The transdermal fentanyl (TDF) patch has become widely used in the
      treatment of cancer pain. We aimed to compare the analgesic efficiency, side
      effects and patient satisfaction of TDF in adult and geriatric patients. METHODS:
      The data of 181 patients who were observed in our pain clinic were included in
      this retrospective study. There were 95 patients in the adult group (Group A) and
      86 patients in the geriatric group (Group G). Demographic data, cancer type,
      duration of pain, side effects, visual analog scale (VAS) score, treatment
      assessment scale (TAS) score, TDF dosage, and the number of patients in whom
      therapy has been terminated were recorded. RESULTS: After the usage of TDF,
      reduction in pain score was observed in both groups (p<0.001). The TAS score was
      similar between the groups at the end of the first month, but it was lower in
      Group G in the following months. Constipation, dry mouth, somnolence, and dyspnea
      were seen more frequently in Group G. Because of these side effects, the number
      of patients in whom therapy was terminated was higher in Group G. CONCLUSION: The
      TDF patch is a good choice for cancer pain treatment for both adult and geriatric
      patients. Since it was observed that the incidence of side effects was higher in
      the geriatric patients, they should be treated more carefully.

PMID- 22865518
TI  - [Evaluation of platelet serotonin levels in migraine without aura].
AB  - OBJECTIVES: The relation between migraine and serotonin levels is not clear.
      Plasma serotonin levels in migraineurs were investigated in previous studies.
      However, in the current literature, it is stated that measurement of serotonin
      level in platelets is more reliable. METHODS: Thirty female migraine without aura
      patients who were diagnosed according to the criteria of the International
      Headache Society and 20 healthy controls were enrolled in the study. The Hamilton
      depression scale (HAM-D) was applied to all subjects and those scoring 10 and
      above were not considered. Fasting venous blood samples were taken from subjects
      in the morning. Platelet rich and poor plasma were prepared. The samples were
      measured with high performance liquid chromatography and platelet serotonin
      concentration was calculated. RESULTS: Our results suggest that migraineurs have
      significantly low platelet serotonin concentration compared to controls. The
      ratio of family history of migraine in the patient group was clearly higher than
      in controls. HAM-D scores were significantly higher in migraineurs than in the
      control group. Although there was a weak correlation between low serotonin levels
      and attack duration and number, there was no statistical significance.
      CONCLUSION: Our results suggest the role of heredity and low serotonin levels in
      the migraine pathogenesis. Even though all subjects enrolled in the study had
      scores under the depression level, HAM-D scores were higher in migraineurs than
      controls. This may indicate the presence of subclinical depression associated
      with low serotonin levels in migraineurs. Extensive studies including both
      serotonin and other markers during pain and pain-free periods are needed.

PMID- 22865519
TI  - [Evaluation of the knowledge, attitude and behaviors of individuals who suffer
      from pain towards complementary and alternative medicines].
AB  - OBJECTIVES: This study was carried out as a descriptive study in order to
      evaluate the knowledge, attitude and behaviors of individuals who suffer from
      pain towards complementary and alternative medicines (CAM). METHODS: The research
      was applied to 535 adult individuals suffering from pain who visited a family
      health center in Erzurum between September 5 and November 30, 2010. The data were
      collected using a questionnaire form and evaluated by computer analysis. RESULTS:
      42.4% of the individuals mentioned that they use CAM in order to eliminate pain,
      83.7% stated that the method they app- lied eliminated their pain, and 39.6% used
      CAM based on a recommendation. It was observed that 95.5% of the participants
      believed that positive thinking helps them recover from their minor diseases,
      91.6% believed that it is necessary to perform more scientific tests on CAM,
      65.6% believed that CAM may be dangerous, 68.4% believed that CAM may be used as
      a last resort, 93.6% believed that they are likely to be ill due to a range of
      stressful events, 61.9% believed that it is worthless to try CAM before seeing a
      doc- tor, 68.2% believed that CAM should not be used for serious diseases, and
      76.3% believed that CAM helps the permanent treatment by strengthening the body's
      own defense. CONCLUSION: It was determined that people who suffer from the pain
      apply for modern medical treatment and have a positive attitude towards CAM.

PMID- 22865520
TI  - [Cervical epidural steroid injections for symptomatic disc herniations].
AB  - OBJECTIVES: Cervical radiculopathy is widespread in society, and the methods used
      in the treatment cover a wide range from conservative treatment to surgical
      treatment. There is not yet a full consensus on the use of invasive approaches
      for the optimal treatment of radicular pain. However, cervical epidural steroid
      injection (CESI) has been used in patients with symptoms of cervical discopathy.
      METHODS: Results of the six-month period of treatment of 58 patients, diagnosed
      as symptomatic cervical radiculopathy with application of CESI within a one-year
      period, were evaluated retrospectively. With the patients in a sitting position
      and with the head flexed, the epidural space was accessed from the C7-T1 aperture
      using the median approach and the hanging drop technique, and a pre- prepared 6
      ml solution consisting of 80 mg triamcinolone with 10 mg levobupivacaine was
      injected following standard sterilization. RESULTS: The post-CESI treatment VAS
      values of the patients were significantly lower than pretreatment VAS values. The
      treatment success rates for CESI application were 93% in the 1st month, 86% in
      the 3rd month, and 72% in the 6th month, respectively. CONCLUSION: The CESI
      application is an effective method in the treatment of cervical radiculopathy and
      reduces the rate of patients needing surgery.

PMID- 22865521
TI  - [Headache case that responded to alendronate treatment in Paget's disease].
AB  - Paget's disease of the bone is a chronic, focal skeletal disease characterized by
      bone pain and deformity, pathological fractures and neurological symptoms such as
      headache, hearing loss and tinnitus, etc. The frequency of the disease increases
      in later ages. Viral and genetical factors play a role in the etiology. The
      majority of cases are asymptomatic. It is often diagnosed with an incidental
      finding on radiography or with an unexpected high serum alkaline phosphatase
      level. Bone fractures or neurological complications can negatively affect the
      quality of life. Early diagnosis and treatment are thus very important.
      Bisphosphonates are the most frequently used medication in the treatment. We
      present a case who sought medical help because of headache and was diagnosed as
      Paget's disease. Neurological complications and the diagnosis and treatment of
      Paget's disease are reviewed in the literature.

PMID- 22865522
TI  - [A commonly seen cause of abdominal pain: abdominal cutaneous nerve entrapment
      syndrome].
AB  - Although abdominal cutaneous nerve entrapment syndrome (ACNES) is accepted as a
      rare condition, it is a syndrome that should be diagnosed more commonly when the
      clinical signs cannot explain the cause of abdominal pain. Abdominal pain is
      commonly considered by physicians to be based on intra-abdominal causes.
      Consequently, redundant tests and consultations are requested for these patients,
      and unnecessary surgical procedures may be applied. Patients with this type of
      pain are consulted to many clinics, and because their definitive diagnoses cannot
      be achieved, they are assessed as psychiatric patients. Actually, a common cause
      of abdominal wall pain is nerve entrapment on the lateral edge of the rectus
      abdominis muscle. In this paper, we would like to share information about the
      diagnosis and treatment of a patient who, prior to presenting to us, had applied
      to different clinics for chronic abdominal pain and had undergone many tests and
      consultations; abdominal surgery was eventually decided.

PMID- 22865523
TI  - Can we use ''coin sign'' image to predict block success after performance of
      sciatic nerve block?

PMID- 22865524
TI  - Clinical efficacy and safety of Securflux(r), an anti-reflux device for
      intravenous infusion.
AB  - PURPOSE: Catheter obstruction or patency inhibition of the venous access cannula
      is a frequently experienced problem in patients to whom intravenous (IV)
      solutions are administered. In this study we assessed the efficacy and safety of
      Securflux(r) a disposable device with a back-check valve to prevent reflux in IV
      infusion sets. METHODS: A total of 177 adult patients requiring IV medication for
      at least 24 hours duration were randomized into two groups: with and without the
      use of Securflux(r). Assessments were performed the 10 days after catheter
      insertion, over three daily visits. The incidence of the onset of reflux
      (visual/non-visual) and the consequences of reflux for both the patient and
      healthcare staff were assessed. RESULTS: There were 4577 follow-up (study) visits
      (53.4% in patients with Securflux(r) and 46.6% without Securflux(r)). Venous
      reflux was observed in 14.2% of all visits, more frequently without Securflux(r)
      (21.3% vs. 8.1%; P<.05). Reflux was mostly visual without Securflux(r) (7.6% vs.
      0.7%) and non-visual with Securflux(r) (13.6% vs. 7.3%). The onset of venous
      reflux carried more consequences, such as inhibition of the line and patient
      discomfort, in the infusions without Securflux(r) (81.1% vs. 73.5% of the visits;
      P<.05). There were no safety concerns related to Securflux(r). CONCLUSIONS:
      Securflux(r) is effective, safe and useful for the prevention of venous reflux
      onset in patients administered IV medication.

PMID- 22865525
TI  - Thermodilution versus saline dilution method for vascular access blood flow
      measurement in high-flux and on-line hemodiafiltration.
AB  - PURPOSE: Access blood flow (Qa) measurements are one of the most important
      components in vascular access monitoring programs, even though these indirect
      methods have only been validated with high-flux hemodialysis (HF; pump flow [Qb]
      300 mL/min). This study was to assess the utility from thermodilution (BTM) with
      respect to the saline dilution method (SDM) in HF and on-line hemodiafiltration
      (OL-HDF) with routinely prescribed parameters in comparison with validation
      conditions. METHODS: Three consecutive sessions were assessed in 31 hemodialysis
      patients (27AVF). The Bland-Altman method and Lin's concordance coefficient
      (rhoc) were used to study accuracy and precision. We used the student t test for
      the analysis of Qa-value in the different subgroups. RESULTS: In HF-hemodialysis
      1 (Qb 300 mL/min), Qa was 1109 +/- 541 mL/min SDM(a) and 1213 +/- 639 mL/min BTM
      (P=.993(a); bias 103.7 mL/min and rhoc 0.78). In HF-hemodialysis 2 (Qb 420
      mL/min) Qa 1071 +/- 578 mL/min SDM (P=1.0(a); -38.2 mL/min and 0.96) and 1216 +/-
      667 mL/min BTM (P=.992(a); 127.3 mL/min and 0.70). In OL-HDF hemodialysis 3 (Qb
      420 mL/min) Qa 1071 +/- 510 mL/min SDM (P=1.0(a); -48.4 mL/min and 0.96) and 1219
      +/- 580 mL/min BTM (P=.977(a); 99.2 mL/min and 0.75). Statistically significant
      differences were only obtained in patients aged >= 65 years old (P=.016) and
      peripheral vascular disease (P=.007). CONCLUSIONS: Our results demonstrate how
      the saline dilution method was more accurate than thermodilution in the HF and OL
      HDF modalities with routinely prescribed parameters. Finally, in this study,
      advanced age (>65 years old) and peripheral vascular disease were associated with
      a significantly lower Qa-value.

PMID- 22865526
TI  - Ultrasound guided supraclavicular central vein cannulation in adults: a technical
      report.
AB  - PURPOSE: Ultrasound-guided (USG) central vein cannulation has become very popular
      among anesthesiologists and critical care physicians in the last decade and it
      has been advocated as the gold standard practice for internal jugular vein (IJV)
      catheterization. METHODS: We report a technique used at our second level hospital
      for cannulating either subclavian vein or innominate vein using a supraclavicular
      (SCV) approach under real time ultrasound guidance for elective positioning of
      long, medium or short-term central venous catheters (CVC). We report one year of
      practice. RESULTS: A total of 347 intravascular devices were positioned;
      successful USG SCV cannulation with no complication, failure or malposition was
      reported in 119 cases. CONCLUSIONS: The SCV approach under ultrasound guidance is
      feasible and safe.

PMID- 22865527
TI  - Recanalization of chronic refractory central venous occlusions utilizing a
      radiofrequency guidewire perforation technique.
AB  - PURPOSE: To assess the technical success rate and safety of radiofrequency
      perforation guidewire (RF) technology for the recanalization of refractory
      chronic central venous occlusions in symptomatic hemodialysis patients with
      failed conventional endovascular methods. METHODS: This single center
      retrospective cohort of hemodialysis patients comprised of six men (mean age 67
      years, range 55 to 80) with autogenous fistulae, who had already undergone failed
      conventional endovascular methods. These patients underwent the RF perforation
      technique from December 2006 to January 2010. RESULTS: Three patients were
      successfully treated using the RF perforation technique, after which they had
      PTFE stent grafts placed at the site of occlusion. There was no recurrence of
      clinical symptoms. In the remaining three patients, the procedure was terminated
      after multiple unsuccessful attempts. There were no complications. CONCLUSIONS:
      The RF perforation technique is a potential alternative technology for
      recanalization of refractory chronic central venous occlusions in hemodialysis
      patients in the setting of failed conventional endovascular recanalization
      techniques.

PMID- 22865528
TI  - Vascular access in patients receiving hemodialysis in Libya.
AB  - PURPOSE: A native arteriovenous fistula (AVF) represents the optimal form of
      Vascular Access (VA) for patients receiving hemodialysis (HD). In Libya there are
      several barriers to AVF creation including lack of adequate preparation for
      dialysis and surgical services. We aimed to conduct the first comprehensive study
      of VA utilisation in HD patients in Libya. METHODS: A prospective observational
      study included all adult patients receiving HD treatment in 25 HD facilities in
      Libya from May 2009 to Nov 2011. Researchers gathered data regarding VA through
      interviews with staff and patients as well as medical records. Patients with
      definitive VA were re-interviewed after 1 year. RESULTS: At baseline the majority
      of patients (91.9%; n=1573) were using permanent VA in the form of AVF or
      arteriovenous graft. Patients with permanent VA were more likely to be male and
      less likely to be diabetic than those with CVCs. Most patients had commenced HD
      using a temporary CVC (91.8%). VA-related complications were: thrombosis (46.7%),
      aneurysm (22.6%), infection (11.5%) and haemorrhage (10.2%). Incident VA
      thrombosis was reported by 14.7% in 1 year. Independent risk factors for incident
      thrombosis were female gender and diabetes. Hospitalisation for VA related
      complications was reported by 31.4%. CONCLUSIONS: Few patients in Libya initiate
      HD with definitive VA, but most achieve it thereafter. Improved dialysis
      preparation and increased provision of surgical services are required to increase
      the proportion of patients initiating HD with definitive VA and should be a
      priority in rebuilding health services in Libya after the recent conflict.

PMID- 22865529
TI  - Permanent central venous catheter for hemodialysis in children with
      myelomeningocele.

PMID- 22865530
TI  - Should functioning AV fistulas be ligated after renal transplantation?
AB  - PURPOSE: There is limited literature available to guide physicians on a course of
      action when they are approached by renal transplant recipients regarding the
      status of their vascular accesses. However, this is a frequent topic of
      discussion with these patients and there should be guidelines available to assist
      in the decision of whether to maintain or ligate an arteriovenous fistula (AVF)
      in a successful renal transplant patient. This review intends to present some of
      the literature, as well as to establish guidelines for management. METHODS: The
      medical literature was reviewed and anecdotal information from our clinical
      experience was collected. RESULTS: Taking into account 10-year adjusted renal
      transplant graft survival rates, and the relative paucity of donors, it is
      possible that a successfully transplanted patient will have to return to dialysis
      at some point. After review of the literature, the impact of AVF ligation on the
      transplant patient's cardiac morphology and function is not clear. Patient and
      graft survival do not appear to be impacted by persistent AVFs. Emergent closure
      of the AVF might be required in cases of severe venous hypertension, risk of
      rupture from pseudoaneurysm, significant high output cardiac failure or ischemic
      hand. CONCLUSIONS: We recommend that following successful renal transplantation,
      functioning AVFs should almost never be ligated. Many patients require return to
      dialysis and the physiologic impact of the patent AVF on these patients does not
      strongly advocate routine ligation following transplant.

PMID- 22865531
TI  - Arteriovenous fistula failure: is there a role for accessory draining vein
      embolization?
AB  - PURPOSE: Arterio-venous fistulae (AVFs) are accepted as the best form of
      haemodialysis vascular access (VA) but are plagued by high primary failure.
      Accessory drainage veins (ADVs) may account for up to 40% of these failures.
      Furthermore, they may also lead to low flow in 'mature' AVFs. METHODS: We
      analysed the results of 42 patients who underwent endovascular coiling of ADVs at
      our centre over a 4-year period. RESULTS: Indications were failure to mature in
      34%, low flow or cannulation difficulty in 56% and thrombosis in 10% of cases.
      95% procedures involved a combination of angioplasty and coiling with only 5%
      patients having coiling of ADV alone. Forearm AVFs constituted the majority of
      the cases as opposed to upper arm AVFs (74% vs. 26% respectively). Primary
      patency at 3, 6, 12, 18 and 24 months was 90%, 87%, 76%, 70% and 55%
      respectively. Successful dialysis was achieved in 10 of the 14 fistulae that had
      hitherto failed to mature. Coil migration was observed in 1 patient, which led to
      fistula occlusion. CONCLUSION: Coil embolisation of ADVs is an effective
      treatment option for dysfunctional fistulae that can be performed at the same
      time as angioplasty.

PMID- 22865532
TI  - A rare case of central venous catheter malpositioning in polytraumatic patient
      not recognized by chest x-ray.

PMID- 22865533
TI  - Anthropometric parameters of nutritional assessment as predictive factors of
      arteriovenous fistula malfunction in patients undergoing hemodialysis.
AB  - INTRODUCTION: To evaluate the role of body mass index (BMI), waist circumference
      (W-C) and waist/hip ratio (WHR) on arteriovenous fistula (AVF) dysfunction.
      METHODS: We evaluated 84 HD patients with an average follow-up period of 31.3 +/-
      8.1 months, identifying 8 stenosis (STN) and 17 thrombosis (THR) cases. The
      association between paired variables was tested with Pearson's coefficient (r)
      and p-value, whereas the prognostic value on STN and THR was analysed using Cox's
      regression. The significant independent variables were indentified with an
      inverse step-wise approach defining the data as hazard ratio (HR). A double-event
      (Stenosis/Thrombosis) model, function of Body mass index and Waist/hip ratio was
      used. Arteriovenous fistula survival was assessed with the Kaplan-Meyer curve and
      the calculations were carried out with Graph-Pad. RESULTS: On univariate
      analysis, THR showed direct correlation with BMI (r=0.44, p<0.01), W-C (r=0.39,
      p<0.05) WHR (r=0.37, p<0.01), Hemoglobin (p<0.001), C-Reactive protein (p=0.01),
      Calcium/Phosforus product (p=0.03), Parathyroid hormone (p=0.03) and inverse with
      albumin (p<0.001) and systolic blood pressure (p=0.003). On multivariate
      analysis, BMI variations were not predictive of STN and THR, whereas each unitary
      WHR and W-C increase was predictive of an increase of risk of events (3.8% and
      2.1% respectively). The prognostic power of W-C per STN (HR 1: 1.19; p<0.05) and
      THR (HR: 1.28; p<0.01) remained significant even after being adjusted to account
      for traditional risk factors. CONCLUSIONS: Abdominal obesity increases the risk
      of AVF dysfunction. The W-C and WHR parameters, not BMI, emerge as independent
      STN and THR predictors.

PMID- 22865534
TI  - Outcomes of AngioJet(r) thrombectomy in hemodialysis vascular access grafts and
      fistulas: PEARL I Registry.
AB  - PURPOSE: Results are reported from the PEARL I Registry for procedures where a
      mid-length AngioJet catheter was used for thrombosed hemodialysis arteriovenous
      grafts and fistulae. METHODS: The PEARL I Registry was a prospective,
      multicenter, observational database collecting information on the AngioJet
      procedures for a variety of thrombotic conditions. Patient demographics,
      procedural information, outcome data, and safety information were collected
      through 3 months postprocedure on AngioJet procedures. This paper describes the
      data collected for subjects presenting with hemodialysis access thrombosis.
      RESULTS: A total of 72 (16%) of the 452 subjects enrolled in the PEARL 1 Registry
      had thrombosed hemodialysis access sites. Procedural success was reported in
      66/72 subjects (92%); surgical interventions were required in 6/72 subjects (8%).
      There was a statistically significant improvement (p<0.0001) in vessel occlusion
      from baseline to final angiography. Eighty-eight percent of access sites were
      patent at the end of the procedure and 97% of vessels showed improved occlusion
      status of =1 grades. Among prosthetic grafts, 53% (20/38) remained patent at the
      3-month follow-up, 18% (7/38) were restenosed, and 29% (11/38) rethrombosed.
      Among autologous fistulas, 86% (18/21) remained patent without intervention at
      the 3-month follow-up; 3 fistulas rethrombosed. Four subjects (5%) died; none of
      the deaths were considered related to the AngioJet device or procedure.
      CONCLUSIONS: Outcomes from the PEARL I registry corroborate other studies of
      AngioJet thrombectomy and the overall literature of endovascular thrombectomy
      procedures. A high procedural success rates with acceptable near-term patency
      rates and low rates of adverse events are achieved with AngioJet thrombectomy.

PMID- 22865535
TI  - Minimally invasive basilic vein harvest for arteriovenous fistula transposition
      using a laryngoscope.
AB  - PURPOSE: The standard lengthy surgical incision used for basilic vein
      arteriovenous fistula (AVF) transposition is associated with significant
      discomfort, scarring and risk of wound complications. Minimally invasive vein
      dissection using a laryngoscope is an inexpensive alternative which has been
      successfully used for saphenous vein harvesting and which we have applied to the
      basilic vein for laryngoscopic-assisted AVF transposition (L-AVF/T). METHODS:
      During this technique, the basilic vein is mobilized through two small incisions,
      one in the axilla and the second just proximal to the cubital fossa. Ultrasound
      examination is used to map the location of the largest distal venous branch,
      either the forearm basilic vein or the median cubital vein. An important element
      of exposure is incising the superficial investing fascia longitudinally over the
      vein, allowing the working space to expand. RESULTS: L-AVF/Ts were constructed in
      47 patients during a 20 month time period. Mean age was 62 (18-87) years. Twenty
      five (53%) patients were women, sixteen (34%) were obese and twenty-eight (60%)
      were diabetic. All veins were successfully harvested and there were no neurologic
      injuries. Primary and cumulative patency rates were 80% and 92%, respectively, at
      one year with follow-up ranging between 1-20 months (mean = 4 months).
      CONCLUSIONS: Minimally invasive dissection of the basilic vein for vascular
      access transposition using laryngoscopic assistance is safe, reliable and cost
      efficient with good short-term patency and functional outcomes.

PMID- 22865536
TI  - Restoration of autologous arteriovenous fistula by vascular stripping in a
      hemodialysis patient with venous neointimal hyperplasia.
AB  - A significant number of arteriovenous fistulae fail because of venous neointimal
      hyperplasia-associated vascular blockage. We developed a surgical technique for
      repairing arteriovenous fistulae by surgically removing neointimal hyperplasia
      and vessel re-anastomosis. Here, we report the successful treatment of a case
      that developed arteriovenous fistula stenosis because of venous neointimal
      hyperplasia.

PMID- 22865537
TI  - Valvular heart disease and dialysis access: a case of cardiac decompensation
      after fistula creation.

PMID- 22865538
TI  - A large aneurysm in an arterio-venous fistula for renal access in a pregnant
      young woman.
AB  - Pregnancy is known to increase the risk of aneurysm formation, likely by a
      combination of histological changes in vessel walls associated with the hormones
      of pregnancy and the haemodynamic changes to the circulation. To our knowledge
      this is the first case of a pregnant woman with a brachial-cephalic arterio
      venous fistula (AVF) that had never been needled for haemodialysis, yet became
      hugely aneurysmal during her pregnancy.

PMID- 22865539
TI  - Production of biobutanediols by the hydrogenolysis of erythritol.
AB  - The hydrogenolysis of erythritol using an Ir-ReO(x)/SiO(2) catalyst was performed
      for the production of butanediols, which are widely used as a raw material of
      polymers. The activity and selectivity to butanediols on Ir-ReO(x)/SiO(2) was
      much higher than that on conventional hydrogenolysis catalysts. The maximum
      selectivity to 1,4- and 1,3-butanediols reached 33 and 12 % at 74 % conversion,
      respectively. The erythritol conversion and selectivity to butanediols was almost
      maintained during four repeating tests if small amounts of acid were added to the
      reaction and the catalyst was calcined again. The reaction kinetics, reactivity
      trends, and characterization results indicate a direct hydrogenolysis mechanism
      in which the hydride species on the Ir metal surface attacks the alkoxide species
      on the 3D ReO(x) clusters. Based on the production of erythritol by the
      fermentation of glucose and glycerol, erythritol hydrogenolysis may be a
      promising pathway for the production of biobutanediols.

PMID- 22865540
TI  - Polychromatic decoupling of a manifold of homonuclear scalar interactions in
      solution-state NMR.
AB  - Window-acquired tetrachromatic irradiation allows one to decouple simultaneously
      four amide protons in cyclosporine A (wavy arrows; see figure) leading to
      simplified multiplets of the alpha protons. By inserting a manifold of
      polychromatic pulses in each dwell time, several subsystems can be decoupled
      simultaneously.

PMID- 22865541
TI  - Induction of heat shock proteins in cerebral cortical cultures by celastrol.
AB  - Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS)
      are 'protein misfolding disorders' of the mature nervous system that are
      characterized by the accumulation of protein aggregates and selective cell loss.
      Different brain regions are impacted, with Alzheimer's affecting cells in the
      cerebral cortex, Parkinson's targeting dopaminergic cells in the substantia nigra
      and ALS causing degeneration of cells in the spinal cord. These diseases differ
      widely in frequency in the human population. Alzheimer's is more frequent than
      Parkinson's and ALS. Heat shock proteins (Hsps) are 'protein repair agents' that
      provide a line of defense against misfolded, aggregation-prone proteins. We have
      suggested that differing levels of constitutively expressed Hsps (Hsc70 and
      Hsp27) in neural cell populations confer a variable buffering capacity against
      'protein misfolding disorders' that correlates with the relative frequencies of
      these neurodegenerative diseases. The high relative frequency of Alzheimer's may
      due to low levels of Hsc70 and Hsp27 in affected cell populations that results in
      a reduced defense capacity against protein misfolding. Here, we demonstrate that
      celastrol, but not classical heat shock treatment, is effective in inducing a set
      of neuroprotective Hsps in cultures derived from cerebral cortices, including
      Hsp70, Hsp27 and Hsp32. This set of Hsps is induced by celastrol at 'days in
      vitro' (DIV) 13 when cultured cortical cells reached maturity. The inducibility
      of a set of neuroprotective Hsps in mature cortical cultures at DIV13 suggests
      that celastrol is a potential agent to counter Alzheimer's disease, a
      neurodegenerative 'protein misfolding disorder' of the adult brain that targets
      cells in the cerebral cortex.

PMID- 22865542
TI  - Biomaterials immobilized with chitosan for rechargeable antimicrobial drug
      delivery.
AB  - Microbial contamination on medical device material surfaces causes serious
      problems including device-related infections. Here we report a new strategy to
      produce rechargeable antimicrobial biomaterial surfaces to address the issue.
      Methacrylic acid (MAA) was grafted onto the surfaces of polyurethane (PU), a
      widely used biomaterial with excellent biological and mechanical properties.
      Chitosan was covalently bonded onto the MAA-grafted surfaces. The new chitosan
      containing PU strongly bound and then slowed release anionic antibiotics (e.g.,
      rifampin) for weeks to months to kill microbes. The released drug could be
      recharged with the same or a different class of drugs to further extend
      antimicrobial duration. Also, the new surfaces demonstrated good biocompatibility
      against mammal cells, pointing to great potentials for a wide range of biomedical
      applications.

PMID- 22865543
TI  - Diagnostic and statistical manual of mental disorders: a classification of
      personality disorders that has had its day.

PMID- 22865544
TI  - HIV-1 control after transient antiretroviral treatment initiated in primary
      infection: role of patient characteristics and effect of therapy.
AB  - BACKGROUND: The occurrence of viral control after interruption of an
      antiretroviral treatment (ART) initiated during primary HIV-1 infection (PHI) is
      rare and the frequency and predictive factors of such a control are unknown.
      METHODS: Within the French ANRS PRIMO Cohort, 164 patients interrupted ART
      initiated during PHI. We compared patients whose viral load (VL) remained
      undetectable (<50 copies/ml) or low (50-500 copies/ml) 1 year after ART
      interruption to those who evidenced a rapid viral rebound. RESULTS: After ART
      interruption, VL remained undetectable for a median time of 4.5 years in 14
      patients ('post-ART controllers') and low in another 14 patients for a median
      time of 1.5 years. Post-ART controllers also maintained higher CD4(+) T-cell
      counts compared to other patients. Female gender, a high CD4(+) T-cell count and
      low VL during PHI, and a high CD4(+) T-cell count and low HIV DNA levels at
      interruption, were associated with post-ART HIV control. Treatment
      characteristics did not differ between controllers and non-controllers. Post-ART
      controllers had lower specific CD8(+) T-cell frequencies and CD8(+) T-cell
      activation on ART and after ART interruption than non-controllers. CONCLUSIONS:
      Few patients maintain very low VL after interruption of treatment initiated
      during PHI. Early patient characteristics were the main factors of viral control,
      although early initiation of ART and the effect of ART on reservoir might
      contribute to control.

PMID- 22865545
TI  - Unchanged prevalence of Down syndrome in the Netherlands: results from an 11-year
      nationwide birth cohort.
AB  - OBJECTIVE: This study aims to evaluate trends in prevalence of Down syndrome (DS)
      births in the Netherlands over an 11-year period and how they have been affected
      by maternal age and introduction of prenatal screening. METHOD: Nationwide data
      of an 11-year birth cohort (1997-2007) from the Netherlands Perinatal Registry
      were analyzed. First-trimester combined screening was introduced in 2002, free of
      charge only for women 36 years of age or older and only on patients' request.
      Changes in maternal age, prevalence of DS births, and rates of births at <24
      weeks (legal limit for termination of pregnancy in the Netherlands) during the
      study period were evaluated using logistic and linear regression analyses.
      RESULTS: In total, 1,972,058 births were registered (91% of the births in 1997
      2007). Mean prevalence of DS was 14.57 per 10,000 births (95% confidence interval
      14.43; 14.73); 85% of DS were live births. No significant trend in overall
      prevalence of DS births was observed (p = 0.385), in spite of a significant
      increase of mean maternal age during the same period (p < 0.001). The increased
      prevalence of DS births at >= 24 weeks among women >= 36 years of age (p = 0.011)
      was offset by a significant increase in the proportion of DS births at <24 weeks
      among women aged <36 years (p = 0.013). CONCLUSION: The proportion of DS births
      in the Netherlands has not changed during the period 1997-2007.

PMID- 22865547
TI  - Missed opportunities to treat: syphilis in pregnancy.

PMID- 22865546
TI  - Correlations among risk-standardized mortality rates and among risk-standardized
      readmission rates within hospitals.
AB  - BACKGROUND: Hospital-level, 30-day risk-standardized mortality and readmission
      rates are publicly reported for Medicare patients admitted with acute myocardial
      infarction (AMI), heart failure (HF), and pneumonia, but the correlations among
      mortality rates and among readmission rates within US hospitals for these
      conditions are unknown. Correlation among measures within the same hospital would
      suggest that there are common hospital-wide quality factors. METHODS: We designed
      a cross-sectional study of US hospital 30-day risk-standardized mortality and
      readmission rates for Medicare fee-for-service beneficiaries from July 2007 to
      June 2009. We assessed the correlation between pairs of risk-standardized
      mortality rates and pairs of risk-standardized readmission rates for AMI, HF, and
      pneumonia. RESULTS: The mortality cohort included 4559 hospitals, and the
      readmission cohort included 4468 hospitals. Every mortality measure was
      significantly correlated with every other mortality measure (range of correlation
      coefficients, 0.27-0.41, P < 0.0001 for all correlations). Every readmission
      measure was significantly correlated with every other readmission measure (range
      of correlation coefficients, 0.32-0.47, P < 0.0001 for all correlations). For
      each condition pair and outcome, one-third or more of hospitals were in the same
      quartile of performance. Correlations were highest within large, nonprofit,
      urban, and/or Council of Teaching Hospitals members. For any given condition
      pair, the correlation between readmission rates was significantly higher than the
      correlation between mortality rates (P < 0.01 for all pairs). CONCLUSION: Risk
      standardized readmission rates are moderately correlated with each other within
      hospitals, as are risk-standardized mortality rates. This suggests that there may
      be common hospital-wide factors affecting hospital outcomes.

PMID- 22865548
TI  - Safety analysis of vagal nerve stimulation for continuous nerve monitoring during
      thyroid surgery.
AB  - OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring (IONM) facilitates
      recurrent laryngeal nerve (RLN) identification, but various studies affirm
      virtually unchanged postoperative RLN palsy rates. Several authors meanwhile
      suggest continuous intraoperative neuromonitoring (CIONM) via vagal nerve
      stimulation (VNS) to improve RLN protection. However, knowledge of side effects
      of electrical VNS derives mainly from its therapeutic applications in the fields
      of neurology and psychiatry. The presented study was conducted to further
      evaluate the safety of CIONM and identify possible VNS related side effects.
      STUDY DESIGN: Prospective nonrandomized controlled trail. METHODS: Forty patients
      scheduled for thyroid or parathyroid surgery were enrolled in the trail. The
      intervention group consisted of 22 patients receiving VNS for CIONM. Eighteen
      patients were operated on with routine IONM. To assess VNS-induced effects on the
      autonomic nervous system (ANS), heart rate variability analysis (HRVA) was
      applied. Serum cytokine levels of tumor necrosis factor (TNF)-alpha were
      monitored to evaluate immunomodulatory effects of VNS. RESULTS: HRVA revealed
      significantly increased vagal activity during CIONM. This parasympathetic
      predominance was not countered by the sympathetic nervous system. Despite a
      significant increase of vagal tone, no hemodynamic events occurred; in fact, no
      significant changes in median heart rate or in median arterial blood pressure
      were detected. Even though anti-inflammatory effects of VNS have been reported,
      no attenuation of cytokine release of TNF-alpha was measured. CONCLUSIONS: VNS
      for CIONM resulted in increased vagal activity assessable via HRVA. The increased
      parasympathetic tone affected neither hemodynamics nor levels of the
      proinflammatory cytokine TNF-alpha. VNS for CIONM appears safe with the applied
      settings.

PMID- 22865549
TI  - Muscarinic receptor stimulation augments TGF-beta1-induced contractile protein
      expression by airway smooth muscle cells.
AB  - Acetylcholine (ACh) is the primary parasympathetic neurotransmitter in the
      airways. Recently, it was established that ACh, via muscarinic receptors,
      regulates airway remodeling in animal models of asthma and chronic obstructive
      pulmonary disease (COPD). The mechanisms involved are not well understood. Here,
      we investigated the functional interaction between muscarinic receptor
      stimulation and transforming growth factor (TGF)-beta(1) on the expression of
      contractile proteins in human airway smooth muscle (ASM) cells. ASM cells
      expressing functional muscarinic M(2) and M(3) receptors were stimulated with
      methacholine (MCh), TGF-beta(1), or their combination for up to 7 days. Western
      blot analysis revealed a strong induction of sm-alpha-actin and calponin by TGF
      beta(1), which was increased by MCh in ASM cells. Immunocytochemistry confirmed
      these results and revealed that the presence of MCh augmented the formation of sm
      alpha-actin stress fibers by TGF-beta(1). MCh did not augment TGF-beta(1)-induced
      gene transcription of contractile phenotype markers. Rather, translational
      processes were involved in the augmentation of TGF-beta(1)-induced contractile
      protein expression by muscarinic receptor stimulation, including phosphorylation
      of glycogen synthase kinase-3beta and 4E-binding protein 1, which was enhanced by
      MCh. In conclusion, muscarinic receptor stimulation augments functional effects
      of TGF-beta(1) in human ASM cells on cellular processes that underpin ASM
      remodeling in asthma and COPD.

PMID- 22865550
TI  - Acute mechanical forces cause deterioration in lung structure and function in
      elastase-induced emphysema.
AB  - The relation between the progression of chronic obstructive pulmonary disease
      (COPD) and exacerbations is unclear. Currently, no animal model of acute
      exacerbation of COPD (AECOPD) exists. The objectives of this study were to
      evaluate the effects of mechanical forces induced by deep inspirations (DIs) on
      short-term deterioration of lung structure and function to mimic AECOPD. At 2, 7,
      or 21 days after treatment with elastase, mice were ventilated with or without
      DIs (35 cmH(2)O airway pressure for 3 s, 2 times/min) for 1 h. Functional
      residual capacity (FRC) was measured with body plethysmography, and respiratory
      compliance, resistance, and hysteresivity were obtained via forced oscillations.
      From hematoxylin and eosin-stained sections, equivalent airspace diameters (D),
      alveolar wall thickness (W(t)), number of septal ruptures (N(sr)), and attachment
      density (A(d)) around airways were determined. FRC, compliance, and hysteresivity
      statistically significantly increased with time, and both increased due to DIs.
      Interestingly, DIs also had an effect on FRC, compliance, resistance, and
      hysteresivity in control mice. The development of emphysema statistically
      significantly increased D and W(t) in time, and the DIs caused subtle differences
      in D. At 21 days, the application of DIs changed the distribution of D, increased
      W(t) and N(sr), and decreased A(d). These results suggest that once a critical
      remodeling of the parenchyma has been reached, acute mechanical forces lead to
      irreversible changes in structure and function, mimicking COPD exacerbations.
      Thus, the acute application of DIs in mice with emphysema may serve as a useful
      model of AECOPD.

PMID- 22865551
TI  - Pathogenetic and predictive value of biomarkers in patients with ALI and lower
      severity of illness: results from two clinical trials.
AB  - Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of
      acute lung injury (ALI) have previously been associated with poorer clinical
      outcomes and increased disease severity among patients with ALI. Whether these
      biomarkers have predictive value in a less severely ill population that excludes
      septic patients with high APACHE II scores is currently unknown. We tested the
      association of plasma and BAL biomarkers with physiological markers of ALI
      severity or clinically relevant outcomes in a secondary analysis of a clinical
      trial of activated protein C for the treatment of ALI. Plasma plasminogen
      activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly
      associated with increased oxygenation index (P = 0.02 and 0.01, respectively),
      whereas there was a trend toward an association between IL-6 and oxygenation
      index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were
      all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01,
      0.01, and 0.05, respectively); no markers were associated with mortality, but we
      hypothesized that this was due to the small size of our cohort and the low death
      rate. To confirm these associations in a larger sample, we identified a
      restricted cohort of patients from the ARDS Network ALVEOLI study with similar
      baseline characteristics. We retested the associations of the significant
      biomarkers with markers of severity and clinical outcomes and studied IL-8 as an
      additional biomarker given its important predictive value in prior studies. In
      this restricted cohort, IL-6 was significantly associated with oxygenation index
      (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased
      28-day mortality. Future studies should be focused on examining larger numbers of
      patients with less severe ALI to further test the relative predictive value of
      plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs
      and mortality, and for their prospective utility in risk stratification for
      future clinical trials.

PMID- 22865552
TI  - STAT6 regulates natural helper cell proliferation during lung inflammation
      initiated by Alternaria.
AB  - Asthma exacerbations can be caused by a number of factors, including the fungal
      allergen Alternaria, which is specifically associated with severe and near-fatal
      attacks. The mechanisms that trigger lung responses are unclear and might vary
      between allergens. A comparison between Alternaria, Aspergillus, Candida, and
      house dust mite, all allergens in humans, showed that only Alternaria promoted
      immediate innate airway eosinophilia within 12 h of inhalation in nonsensitized
      mice. Alternaria, but not the other allergens, induced a rapid increase in airway
      levels of IL-33, accompanied by IL-33 receptor (IL-33R)-positive natural helper
      cell (NHC) production of IL-5 and IL-13. NHCs in the lung and bone marrow
      constitutively expressed transcription factors [GATA-3 and E26 transformation
      specific sequence-1 (ETS-1)] that could allow for rapid induction of T helper
      type 2 (Th2) cytokines. Lung NHC numbers and proliferation (%Ki-67), but not IL-5
      or GATA-3 expression, were significantly reduced in STAT6-deficient mice 3 days
      after one challenge with Alternaria. Alternaria induced NHC expression of the EGF
      receptor ligand amphiregulin (partially dependent on STAT6), as well as EGF
      receptor signaling in the airway epithelium. Finally, human peripheral blood NHCs
      (CRTH2(+)CD127(+) lineage-negative lymphocytes) from allergic individuals highly
      expressed GATA-3 and ETS-1, similar to lung NHCs in mice. In summary, Alternaria
      induced lung NHC proliferation and expression of amphiregulin are regulated by
      STAT6. In addition, NHCs in mouse and humans are primed to express Th2 cytokines
      through constitutive expression of GATA-3 and ETS-1. Thus several transcription
      factor pathways (STAT6, GATA-3, and ETS-1) may contribute to NHC proliferation
      and Th2-type responses in Alternaria-induced asthma.

PMID- 22865553
TI  - NOX2 (gp91phox) is a predominant O2 sensor in a human airway chemoreceptor cell
      line: biochemical, molecular, and electrophysiological evidence.
AB  - Pulmonary neuroepithelial bodies (NEBs), composed of clusters of amine [serotonin
      (5-HT)] and peptide-producing cells, are widely distributed within the airway
      mucosa of human and animal lungs. NEBs are thought to function as airway O(2)
      sensors, since they are extensively innervated and release 5-HT upon hypoxia
      exposure. The small cell lung carcinoma cell line (H146) provides a useful model
      for native NEBs, since they contain (and secrete) 5-HT and share the expression
      of a membrane-delimited O(2) sensor [classical NADPH oxidase (NOX2) coupled to an
      O(2)-sensitive K(+) channel]. In addition, both native NEBs and H146 cells
      express different NADPH oxidase homologs (NOX1, NOX4) and its subunits together
      with a variety of O(2)-sensitive voltage-dependent K(+) channel proteins (K(v))
      and tandem pore acid-sensing K(+) channels (TASK). Here we used H146 cells to
      investigate the role and interactions of various NADPH oxidase components in O(2)
      sensing using a combination of coimmunoprecipitation, Western blot analysis
      (quantum dot labeling), and electrophysiology (patchclamp, amperometry) methods.
      Coimmunoprecipitation studies demonstrated formation of molecular complexes
      between NOX2 and K(v)3.3 and K(v)4.3 ion channels but not with TASK1 ion
      channels, while NOX4 associated with TASK1 but not with K(v) channel proteins.
      Downregulation of mRNA for NOX2, but not for NOX4, suppressed hypoxia-sensitive
      outward current and significantly reduced hypoxia -induced 5-HT release.
      Collectively, our studies suggest that NOX2/K(v) complexes are the predominant
      O(2) sensor in H146 cells and, by inference, in native NEBs. Present findings
      favor a NEB cell-specific plasma membrane model of O(2)-sensing and suggest that
      unique NOX/K(+) channel combinations may serve diverse physiological functions.

PMID- 22865554
TI  - Clinicopathological study in progressive supranuclear palsy with pedunculopontine
      stimulation.
AB  - BACKGROUND: Pedunculopontine nucleus (PPN) DBS has emerged as a potential
      intervention for patients with gait and balance disorders. However, targeting
      this nucleus can be challenging. We report on the first neuropathological
      analyses after PPN-DBS surgery in advanced progressive supranuclear palsy (PSP).
      METHODS: Two patients with PSP underwent unilateral PPN-DBS surgery and were
      clinically followed to autopsy. Both patients underwent postmortem
      neuropathological analysis, including choline acetyltransferase
      immunohistochemistry, to ascertain PPN boundaries and electrode location.
      RESULTS: Both patients experienced partial improvement in some motor and nonmotor
      domains postintervention, but died shortly of other complications. Postmortem
      neuropathological analysis of each patient confirmed the electrode in a region of
      cholinergic neuronal loss corresponding to the PPN. CONCLUSIONS: We provide
      histopathological evidence for the validity of our stereotactic approach to
      target the PPN and correlate electrode location with clinical outcomes.

PMID- 22865557
TI  - Watching the methanol-to-olefin process with time- and space-resolved high-energy
      operando X-ray diffraction.

PMID- 22865558
TI  - Polarization rotation in the monoclinic perovskite BiCo(1-x)Fe(x)O3.

PMID- 22865555
TI  - Poly(2-oxazoline)s as polymer therapeutics.
AB  - Poly(2-oxazoline)s (POx) are currently discussed as an upcoming polymer platform
      for biomaterials design and especially for polymer therapeutics. POx meet
      specific requirements needed for the development of next-generation polymer
      therapeutics such as biocompatibility, high modulation of solubility, variation
      of size, architecture as well as chemical functionality. Although in the early
      1990s first and promising POx-based systems were presented, the field lay dormant
      for almost two decades. Only very recently, POx-based polymer therapeutics came
      back into the focus of very intensive research. In this review, we give an
      overview on the chemistry and physicochemical properties of POx and summarize the
      research of POx-protein conjugates, POx-drug conjugates, POx-based polyplexes and
      POx micelles for drug delivery.

PMID- 22865559
TI  - Investigation of "on water" conditions using a biphasic fluidic platform.

PMID- 22865560
TI  - An ionothermal synthetic approach to porous polyoxometalate-based metal-organic
      frameworks.

PMID- 22865561
TI  - Catalyst-free N-arylation using unactivated fluorobenzenes.

PMID- 22865562
TI  - Total synthesis of (+)-davidiin.

PMID- 22865563
TI  - Asymmetric syntheses of 8-oxabicyclo[3,2,1]octanes: a cationic cascade
      cyclization.

PMID- 22865564
TI  - Characterization of microfluidic gas reactors using remote-detection MRI and
      parahydrogen-induced polarization.

PMID- 22865565
TI  - Hypoiodite-mediated metal-free catalytic aziridination of alkenes.

PMID- 22865566
TI  - Imaging latent fingerprints by electrochemiluminescence.

PMID- 22865567
TI  - Gallium tribromide catalyzed coupling reaction of alkenyl ethers with ketene
      silyl acetals.

PMID- 22865568
TI  - Selective iodine-catalyzed intermolecular oxidative amination of C(sp3)-H bonds
      with ortho-carbonyl-substituted anilines to give quinazolines.

PMID- 22865569
TI  - Intramolecular C-H bond activation through a flexible ester linkage.

PMID- 22865570
TI  - Combined electrochemistry and surface-enhanced infrared absorption spectroscopy
      of gramicidin A incorporated into tethered bilayer lipid membranes.

PMID- 22865571
TI  - Comparative study of collagen hydrogels modified in two ways using the model of
      ectopic cartilage construction with diffusion-chamber in immunocompetent host.
AB  - PURPOSE: For scaffolds in cartilage tissue engineering, it is the principle to
      design the materials with both favorable mechanical and biological property.
      METHODS: In this article, collagen hydrogels modified by two ways to improve
      mechanical strength were applied for in vivo cartilage reconstruction: one is
      collagen-alginate hydrogel (CAH) representative of mixture, the other is collagen
      hydrogel crosslinked by genipin (CGH). To investigate the biological activities
      of the two materials, it was designed as: scaffolds loaded with allogenous
      chondrocytes were encased in diffusion chamber, and then implanted subcutaneously
      in SD rats for 8 weeks. RESULTS: Histologic, immunohistochemical, and RT-PCR
      results showed that collagen type II and GAG, indicator of cartilage
      extracellular matrix (ECM) was highly expressed in constructs of chondrocyte-CAH.
      Significantly lower cell density and expression of cartilage specific protein
      were shown in constructs of chondrocyte-CGH than that in chondrocyte-CAH. This
      demonstrated that CAH may provide a more favorable environment for cartilage
      reconstruction. In addition, the model with diffusion chamber technique was
      viable for evaluation of scaffolds in vivo cartilage engineering in
      immunocompetent host. Instead, directly reconstruction of ectopic cartilage
      without diffusion chamber suffered from damaged tissue and less neo-cartilage
      matrix formed. CONCLUSIONS: In conclusion, CAH is realistic as scaffold for in
      vivo cartilage tissue engineering with both satisfactory mechanical properties
      and biomimetic activity. And the model with diffusion chamber to reconstruct
      ectopic cartilage in immunocompetent animals is promising for evaluation of
      scaffolds. This study provided a new insight for in vivo cartilage tissue
      engineering.

PMID- 22865572
TI  - New perspectives in cell delivery systems for tissue regeneration: natural
      derived injectable hydrogels.
AB  - Natural polymers, because of their biocompatibility, availability, and physico
      chemical properties have been the materials of choice for the fabrication of
      injectable hydrogels for regenerative medicine. In particular, they are appealing
      materials for delivery systems and provide sustained and controlled release of
      drugs, proteins, gene, cells, and other active biomolecules immobilized.In this
      work, the use of hydrogels obtained from natural source polymers as cell delivery
      systems is discussed. These materials were investigated for the repair of
      cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue.
      Papers from the last ten years were considered, with a particular focus on the
      advances of the last five years. A critical discussion is centered on new
      perspectives and challenges in the regeneration of specific tissues, with the aim
      of highlighting the limits of current systems and possible future advancements.

PMID- 22865573
TI  - Radioactive potential of zirconium-dioxide used for dental applications.
AB  - PURPOSE: The purpose of this study was to investigate the possible radioactive
      potential of zirconium dioxide (ZrO2) dental ceramics. Such information is
      necessary since they became an integral part of routine prosthetic
      rehabilitations and devoid of scientific information about their radioactivity
      creates some concern in the dental community. METHODS: Four different types of
      commercial ZrO2 ceramics, namely Lava, Cercon, ICE Zirkon, and Everest Bio ZS
      were investigated before and after the sintering process. Sintering temperatures
      were applied according to each manufacturer's instructions. The compositions of
      the presintered and sintered specimens were analyzed using x-Ray Fluorescence
      Spectrometer (XRF). Concentrations of the elements and compounds were also
      measured by this method. Determination of radioactivity continued with Gamma
      spectrometry measurements and Gross alpha/Beta analyses. RESULTS: The activity of
      gamma and Gross alpha/beta was below minimum detection limits (MDL) for
      presintered and sintered ZrO2. The MDLs of gross alpha/beta counting system were
      0.02 Bq/g and 0.01 Bq/g for alpha and beta radioactivity, respectively. The
      sintering process played only a minor role in the composition of the compounds.
      CONCLUSIONS: Radioactivity of the ZrO2 ceramics studied showed negligible
      radionuclide activity that can be considered lower than many hazardous
      radioactive appliances in our environment.

PMID- 22865574
TI  - A novel silicon-based electrochemical treatment to improve osteointegration of
      titanium implants.
AB  - BACKGROUND: Titanium and its alloy represent the most commonly used biomaterials
      worldwide designed for bone-contact under-load applications, which often require
      specific mechanical properties. In particular, a large number of different
      biomimetic surface treatments have been developed to speed up the
      osteointegration process, which facilitates a reduction in recovery time.
      PURPOSE: The aim of this work is to investigate the physical-chemical, mechanical
      and bioactivity properties of an innovative biomimetic treatment on titanium
      performed using Anodic Spark Deposition (ASD) electrochemical treatment. METHODS:
      The proposed ASD treatment was obtained in an electrochemical solution containing
      silicon, calcium, phosphorous and sodium followed by an alkali etching. Surface
      morphology was characterized using SEM and laser profilometry. Chemical and
      structural composition was assessed by EDS, ICP/OES and XRD analysis. Vickers
      micro hardness and static contact angle measurements were performed to assess the
      surface mechanical properties and wettability. RESULTS: The proposed anodization
      treatment was capable of providing a chemical and morphologic modified titanium
      oxide layer, adherent and characterized by superhydrophilic properties. The
      microporous morphology was enriched by calcium, silicon, sodium and
      phosphorous.After incubation in Kokubo's Simulated Body Fluid (SBF) the treatment
      showed very high mineralization potential compared to the reference surfaces,
      accounting for a deposited hydroxyapatite layer as thick as 12 MUm after 14 days
      of SBF incubation. CONCLUSIONS: On the basis of the results obtained in this
      study, we believe that the novel silicon-based ASD biomimetic treatment
      represents a promising treatment capable of enhancing the osteointegration of
      titanium for dental and orthopedic applications.

PMID- 22865575
TI  - The effect of material modeling on finite element analysis of human breast
      biomechanics.
AB  - PURPOSE: Finite element analysis has been used extensively in the study of
      biomechanical modeling of the breast. However, issues regarding the complexity of
      material models and the influences of geometric boundary conditions on the
      accuracy of a breast Finite Element (FE) model are still under debate. This work
      demonstrates the importance of material modeling in FE models of the breast.
      METHODS: A simple hemispherical geometry is used to model the shape of a human
      breast. Different material models are being investigated to accurately model
      changes in terms of displacement, stress, and reaction forces distribution.
      RESULTS: The results obtained using nonlinear material models are compared with
      those obtained employing their linear approximation. Results have shown that
      differences, in terms of displacement, ranging between 20% and more than 80%, may
      occur and that large differences are present in terms of maximum principal
      stresses when the displacement is correctly approximated. CONCLUSIONS: This study
      clearly shows that, in a FE model, simulating large deformations material
      modeling strongly influences the accuracy of the solution.

PMID- 22865576
TI  - A randomized trial of mupirocin sinonasal rinses versus saline in surgically
      recalcitrant staphylococcal chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) recalcitrant to surgery is a
      frustrating clinical entity. Recently, mupirocin sinonasal rinses have been
      suggested as an efficacious treatment alternative in these patients where
      Staphylococcus aureus infection is demonstrated. To our knowledge, how best to
      treat this S aureus reservoir has not been previously evaluated in a double
      blinded, randomized, placebo-controlled trial. STUDY DESIGN: Prospective, double
      blinded, placebo-controlled study. METHODS: Twenty-five S aureus-positive CRS
      patients with persistent sinonasal infection despite endoscopic sinus surgery
      received either a 1-month, twice-daily treatment course of mupirocin sinonasal
      rinses (MUP) or saline rinses (CON). The primary outcome was S aureus-culture
      negativity at the conclusion of treatment; secondary rhinological outcomes
      included subjective and objective measures of rhinosinusitis. RESULTS: Twenty-two
      patients satisfactorily completed the treatment period. Of CON patients, 0/13
      (0.0%) returned an S aureus-negative sinonasal culture at 1 month, compared to
      8/9 (88.9%) of MUP patients (P < .01). Improvements in rhinological outcomes
      observed in MUP patients following treatment were not subsequently evident when
      these patients were followed up at a delayed assessment 2 to 6 months after
      completing treatment. CONCLUSIONS: Mupirocin sinonasal rinses are an effective
      short-term anti-S aureus treatment in surgically recalcitrant CRS as assessed by
      microbiological and selected rhinological outcomes, although the latter
      improvements may not be durable with time.

PMID- 22865577
TI  - 1D coaxial platinum/titanium nitride nanotube arrays with enhanced
      electrocatalytic activity for the oxygen reduction reaction: towards Li-air
      batteries.
AB  - CAT ON A HOT TIN SUPPORT: Coaxial Pt/TiN nanotube arrays are used to achieve a
      superior electrocatalytic activity of platinum towards the oxygen reduction
      reaction (ORR). Compared to a commercial Pt/C catalyst, the Pt/TiN NTA materials
      delivers a higher mass activity and specific activity for the ORR. Hence, these
      materials are useful as cathodes for hybrid electrolyte Li-air batteries, as
      demonstrated.

PMID- 22865578
TI  - Two propensity score-based strategies for a three-decade observational study:
      investigating psychotropic medications and suicide risk.
AB  - The US Food and Drug Administration issued separate warnings for suicidality with
      antidepressants and antiepileptic drugs in the past 5 years. This study describes
      methods for examining the association of these agents with suicide attempts and
      suicide deaths in more broadly generalizable samples than examined by the US Food
      and Drug Administration. An observational study of mood disorders was examined
      that includes three decades of prospective assessments. Because of sample size
      differences, two distinct longitudinal implementations of the propensity
      adjustment are used in separate analyses of antidepressants and antiepileptic
      drugs. Propensity score quintile-stratified safety analyses were used with the
      large antidepressant data set; whereas, propensity score matched safety analyses
      were used with the smaller antiepileptic drug data because stratification was not
      feasible. In each case, mixed-effects survival models compared the safety of
      participants when receiving the respective class of medication to periods when
      they did not receive that medication. When participants were more severely ill,
      they were significantly more likely to receive either class of psychotropics.
      Propensity quintile-stratified safety analyses found that risk of suicide
      attempts or suicides was significantly reduced when participants received
      antidepressants. In contrast, propensity score matched safety analyses found
      neither significant risk nor protection from suicidality among participants
      receiving antiepileptics.

PMID- 22865579
TI  - Successful right ventricular lead placement using a right ventricular septal
      stylet in a patient with persistent left superior vena cava.

PMID- 22865580
TI  - 'Unblinding' the cryoballoon.

PMID- 22865581
TI  - Purification and cytotoxicity of tag-free bioengineered spider silk proteins.
AB  - Bioengineered spider silk-like proteins can serve as biomaterials for various
      biomedical applications. These proteins can be assembled in several morphological
      forms such as films, microcapsules, spheres, fibers, gels, and scaffolds.
      However, crucial points for recombinant spider silks for human use are toxicity
      and immunogenicity. To assess this issue, two bioengineered spider silk proteins
      composed of different numbers of repetitive motifs of the consensus repeats from
      spidroin-1 from Nephila clavipes (15X and 6X) were cloned and expressed in
      Escherichia coli. The proteins were free of tag sequence and were purified using
      two methods based on (1) thermal and (2) organic acid resistance of the spider
      silks. The soluble spider silk proteins were not cytotoxic and did not activate
      macrophages over a wide range of concentrations, except when present at the
      highest concentration. Films made of the different silk variants supported the
      growth of the cells. Based on these data, and as the biodegradation rate of silk
      is very slow, the bioengineered spider silks are presumed safe biomaterials for
      biomedical applications.

PMID- 22865582
TI  - Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual
      shift from a Th17 effector cell response to a predominant infiltration by
      regulatory T-cells.
AB  - The type of immune cells that are present within the tumor microenvironment can
      play a crucial role in the survival of patients. However, little is known about
      the dynamics of the tumor-infiltrating immune cells during disease progression.
      We studied the immune cells that infiltrated the tumor tissues of ovarian cancer
      patients at different stages of disease. The early stages of development of
      ovarian carcinomas were characterized by a strong Th17 immune response, whereas
      in stage II patients, recruitment of high numbers of Th1 cells was observed. In
      disseminated tumors (Stages III-IV), we detected a dominant population of
      Helios(+)  activated regulatory T cells (Tregs) along with high numbers of
      monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor-infiltrating
      Tregs had markedly lower expression of CCR4 than circulating Tregs, and the
      numbers of tumor-infiltrating Tregs significantly correlated with the levels of
      CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment
      via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells,
      monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression
      markedly increased in response to IFNgamma. Taken together, the specific
      recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a
      significant immune suppression in the advanced stages of ovarian cancer.

PMID- 22865584
TI  - Basal state hyperinsulinemia in healthy normoglycemic adults heralds dysglycemia
      after more than two decades of follow up.
AB  - BACKGROUND: In a preliminary report, we found an association between
      hyperinsulinemia in the basal (fasting) state and the development of diabetes.
      OBJECTIVES: The current analysis further explored the long term link between
      basal hyperinsulinemia and conversion to dysglycemia. METHODS: This is a
      prospective study with up to 24 years of follow-up of 515 normoglycemic
      individuals (mean age at follow up = 70.3 +/- 7.0; range 58-94) of an Israeli
      cohort. Fasting glucose and insulin were measured, and dysglycemia was defined as
      fasting glucose > 100 mg/dL. RESULTS: At the end of the follow-up period, almost
      half had progressed to dysglycemia. Male sex and elevated baseline levels of
      basal insulin, body mass index, blood glucose and blood pressure each favoured
      progression to dysglycemia over the subsequent two decades. A multivariate
      logistic regression model identified basal hyperinsulinemia as the strongest
      predictor for progression to dysglycemia (odds ratio = 1.79; 95% confidence
      interval 1.12-2.88), while controlling for ethnicity, blood pressure, fasting
      glucose, male sex, body mass index and age. CONCLUSIONS: Basal hyperinsulinemia
      in normoglycemic adults constitutes an independent risk factor for metabolic
      deterioration to dysglycemia over adulthood, and may help to identify apparently
      healthy subjects at increased risk for diabetes.

PMID- 22865585
TI  - Self-recovery of Pd nanoparticles that were dispersed over La(Sr)Fe(Mn)O3 for
      intelligent oxide anodes of solid-oxide fuel cells.
AB  - Self-recovery is one of the most-desirable properties for functional materials.
      Recently, oxide anodes have attracted significant attention as alternative anode
      materials for solid-oxide fuel cells (SOFCs) that can overcome reoxidation,
      deactivation, and coke-deposition. However, the electrical conductivity and
      surface activity of the most-widely used oxide anodes remain unsatisfactory.
      Herein, we report the synthesis of an "intelligent oxide anode" that exhibits
      self-recovery from power-density degradation in the redox cycle by using a Pd
      doped La(Sr)Fe-(Mn)O(3) cell as an oxide anode for the SOFCs. We investigated the
      anodic performance and oxidation-tolerance of the cell by using Pd-doped
      perovskite as an anode and fairly high maximum power densities of 0.5 and 0.1 W
      cm(-2) were achieved at 1073 and 873 K, respectively, despite using a 0.3 mm
      thick electrolyte. Long-term stability was also examined and the power density
      was recovered upon exposure of the anode to air. This recovery of the power
      density can be explained by the formation of Pd nanoparticles, which were self
      recovered through reoxidation and reduction. In addition, the self-recovery of
      the anode by oxidation was confirmed by XRD and SEM and this process was
      effective for improving the durability of SOFC systems when they were exposed to
      severe operating conditions.

PMID- 22865586
TI  - Role of melatonin in the oxidative damage prevention at different times of
      hepatic regeneration.
AB  - The process of regenerating liver is the result of a balance between stimulating
      factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites
      have been found to protect tissues against oxidative damage generated by a
      variety of toxic agents and metabolic processes. Furthermore, studies in liver of
      rats showed a decrease in the liver mitochondrial hydroxylation of drugs
      returning to the normal state after the administration of antioxidants. This
      study was designed to determine, in experimental animals, whether the
      administration of an antioxidant agent such as melatonin could prevent cells
      events leading to tissue injury and hepatic dysfunction after partial hepatectomy
      (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na+/K+ ATPase
      activities in whole plasma membrane were determined. PH decreased the Na+/K+
      ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative
      stress with an increase of lipoperoxidation and decrease of glutathione
      peroxidase and catalase activities. Treatment with melatonin prevented the
      decrease of BF in rats with hepatectomy and normalized the Na+/K+ ATPase
      activity. Moreover, melatonin markedly attenuated oxidative stress produced by
      PH. This may be the results of the higher efficacy of melatonin in scavenging
      various free radicals and also because of its ability in stimulating the
      antioxidant enzymes. We suggest that oxidative stress before and during liver
      regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular
      damage and the impairment in liver transport function induced by PH and that
      melatonin could modulate the degree of oxidative stress and through it prevent
      the alterations in liver function carrier.

PMID- 22865587
TI  - The pill questionnaire in a nondemented Parkinson's disease population.
AB  - We assessed the Pill Questionnaire as a screen for mild cognitive impairment in
      nondemented Parkinson's disease patients. The relationship between ability to
      remember medications for Parkinson's disease in the Pill Questionnaire, mild
      cognitive impairment, and deficits on neuropsychological tests performed 2-3
      weeks later blind to Pill Questionnaire results was assessed in movement
      disorders clinic patients. In 109 subjects, inaccurate medication reporting on
      the Pill Questionnaire was associated with lower scores on the Montreal Cognitive
      Assessment, Scales for Outcomes in Parkinson's Disease-Cognition and with
      deficits in memory, attention, executive function-inhibitory control, processing
      speed, visuospatial function, and language. Inaccurate medication reporting was
      also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91-5.88; P = .06)
      for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%.
      The Pill Questionnaire is neither sensitive nor specific enough to be used as the
      sole screening or diagnostic tool for mild cognitive impairment. However,
      inaccurate medication reporting is associated with deficits spanning many
      cognitive domains and should alert a clinician to a higher likelihood of
      cognitive impairment.

PMID- 22865588
TI  - Glucose-regulated insulin release from acid-disintegrable microgels covalently
      immobilized with glucose oxidase and catalase.
AB  - The fabrication of a novel type of positively charged acid-disintegrable microgel
      loaded with insulin by electrostatic interactions and covalently immobilized with
      glucose oxidase (GOx) and catalase by inverse emulsion polymerization is
      reported, aiming for glucose-regulated insulin release by utilizing GOx/catalase
      cascade enzymatic reactions to trigger local pH decrease and acid-cleavage of
      crosslinking moieties. At the same time, a local pH decrease within the microgels
      also leads to the diminishment of net surface negative charges of encapsulated
      insulin. The above two factors both synergistically contribute to the prominently
      enhanced insulin release at high glucose levels (~10-20 mM) compared to that in
      the absence of glucose.

PMID- 22865589
TI  - Preoperative topical antimicrobial decolonization in head and neck surgery.
AB  - OBJECTIVES/HYPOTHESIS: Surgical site infections (SSIs) are an important cause of
      morbidity and mortality after head and neck surgery. Our primary objective was to
      determine the efficacy of preoperative topical antimicrobial decolonization
      before head and neck surgery. STUDY DESIGN: Prospective, randomized controlled
      trial. METHODS: This study was conducted among 84 patients presenting for head
      and neck surgery requiring admission to an academic medical center. Preoperative
      cultures were performed to identify Staphylococcus aureus carriers. Patients were
      randomized to preoperative topical antimicrobial decolonization with a 5-day
      regimen of chlorhexidine skin rinses and intranasal mupirocin coupled with
      standard perioperative systemic antimicrobial prophylaxis, versus standard
      prophylaxis alone. The main outcome was the incidence of SSIs. RESULTS: Despite a
      trend suggesting a decrease in SSIs with perioperative topical antimicrobial
      decolonization (24% vs. 10%), there was no significant difference (odds ratio,
      0.34; 95% confidence interval, 0.10-1.18; P = .079). Patients with a higher
      American Society of Anesthesiologists score (3 vs. 1; P = .02), with more
      operative blood loss (P = .05), and who required operative takeback (P = .04) had
      a higher rate of SSIs; there was a trend suggesting a higher rate of SSIs among
      patients undergoing clean-contaminated surgery compared to clean cases (P = .08)
      and among those having received prior radiation (P = .07) or chemotherapy (P =
      .06). CONCLUSIONS: Preoperative antimicrobial decolonization did not
      significantly decrease the incidence of SSIs after head and neck surgery, but
      might be considered for high-risk groups despite the lack of conclusive evidence
      confirming efficacy. Risk factors for SSIs after head and neck surgery are
      identified for the first time in a prospective study.

PMID- 22865591
TI  - Adsorbate alignment in surface halogenation: standing up is better than lying
      down.
AB  - Bromine atom transfer to a silicon surface as a function of physisorbed adsorbate
      alignment (see picture: left, vertical 1-bromopentane; right, horizontal 1
      bromopentane) of 1-bromopropane and 1-bromopentane on Si(111)-7*7 has been
      studied by STM. In both thermal and electron-induced bromination reactions, the
      vertical alignment is more reactive.

PMID- 22865590
TI  - Furan carcinogenicity: DNA binding and genotoxicity of furan in rats in vivo.
AB  - SCOPE: Furan is a potent hepatotoxicant and liver carcinogen in rodents. However,
      short-term tests for genotoxicity of furan are inconclusive. The aim of this
      study was to assess the potential of furan to covalently bind to DNA, and to
      assess furan genotoxicity in rats in vivo. MATERIALS AND METHODS: Accelerator
      mass spectrometry was used to determine the (14) C-content in DNA following
      administration of [3,4-(14) C]-furan (0.1 and 2.0 mg/kg bw) to F344 rats. DNA
      damage, micronuclei, chromosomal aberrations, and sister chromatid exchanges were
      analyzed in F344 rats treated with furan for up to 28 days. CONCLUSION: The (14)
      C-content in liver DNA was significantly increased in a dose-dependent manner,
      with mean concentrations of 7.9 +/- 3.5 amol (14) C/MUg DNA and 153.3 +/- 100.2
      amol (14) C/MUg DNA, corresponding to 16.5 +/- 7.4 and 325.2 +/- 212.7
      adducts/10(9)  nucleotides at 0.1 and 2.0 mg/kg bw, respectively. There was no
      evidence for genotoxicity of furan in peripheral blood and bone marrow cells.
      However, a dose-related increase in the incidence of chromosomal aberrations in
      rat splenocytes and some indication of DNA damage in liver were observed.
      Collectively, results from this study indicate that furan may operate-at least in
      part-by a genotoxic mode of action.

PMID- 22865592
TI  - Modulating phonation through alteration of vocal fold medial surface contour.
AB  - OBJECTIVES/HYPOTHESIS: 1) To test whether alteration of the vocal fold medial
      surface contour can improve phonation and 2) to demonstrate that implant material
      properties affect vibration even when implantation is deep to the vocal fold
      lamina propria. STUDY DESIGN: Induced phonation of excised human larynges.
      METHODS: Thirteen larynges were harvested within 24 hours postmortem. Phonation
      threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold
      injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA).
      Small-volume injections (median, 0.0625 mL) were targeted to the inferomedial
      aspect of the thyroarytenoid muscle. Implant locations were assessed
      histologically. RESULTS: The effect of implantation on PTP was material
      dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP
      (Wilcoxon test, P = .00013 for onset). In contrast, the effect of implantation on
      PTF was similar, with both materials tending to decrease PTF (P = .16 for onset).
      Histology confirmed implant presence in the inferior half of the vocal fold
      vertical thickness. CONCLUSIONS: Taken together, these data suggested the
      implants may have altered the vocal fold medial surface contour, potentially
      resulting in a less convergent or more rectangular glottal geometry as a means to
      improve phonation. An implant with a closer viscoelastic match to vocal fold
      cover is desirable for this purpose, as material properties can affect vibration
      even when the implant is not placed within the lamina propria. This result is
      consistent with theoretical predictions and implies greater need for surgical
      precision in implant placement and care in material selection.

PMID- 22865593
TI  - Distinct genetic association at the PLCE1 locus with oesophageal squamous cell
      carcinoma in the South African population.
AB  - Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Black and
      Mixed Ancestry populations of South Africa. Recently, three genome-wide
      association studies in Chinese populations identified five new OSCC
      susceptibility loci, including variants at PLCE1, C20orf54, PDE4D, RUNX1 and
      UNC5CL, but their contribution to disease risk in other populations is unknown.
      In this study, we report testing variants from these five loci for association
      with OSCC in the South African Black (407 cases and 849 controls) and Mixed
      Ancestry (257 cases and 860 controls) populations. The RUNX1 variant rs2014300,
      which reduced risk in the Chinese population, was associated with an increased
      risk of OSCC in the Mixed Ancestry population [odds ratio (OR) = 1.33, 95%
      confidence interval (CI) = 1.09-1.63, P = 0.0055], and none of the five loci were
      associated in the Black population. Since PLCE1 variants increased the risk of
      OSCC in all three Chinese studies, this gene was investigated further by
      sequencing in 46 Black South Africans. This revealed 48 variants, 10 of which
      resulted in amino acid substitutions, and much lower linkage disequilibrium
      across the PLCE1 locus than in the Chinese population. We genotyped five PLCE1
      variants in cases and controls, and found association of Arg548Leu (rs17417407)
      with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the
      Black population. These findings indicate several differences in the genetic
      contribution to OSCC between the South African and Chinese populations that may
      be related to differences in their genetic architecture.

PMID- 22865594
TI  - FK506 alleviates proteinuria in rats with adriamycin-induced nephropathy by down
      regulating TRPC6 and CaN expression.
AB  - BACKGROUND: To investigate the roles of transient receptor potential cation
      channel 6 (TRPC6) and calcineurin (CaN) in proteinuria pathogenesis and the
      mechanism of action of the calcineurin inhibitor tacrolimus (FK506) in adriamycin
      induced nephropathy. METHODS: The adriamycin-induced nephropathy rats were
      established and randomly divided into adriamycin nephropathy (ADR), low-dose
      FK506 treated (ADR + FK0.5), high-dose FK506 treated (ADR + FK1.0) and Control
      groups. Twenty-four hour urinary protein and blood biochemistry were measured on
      weeks 2, 3, 5 and 7, and the distributions and expressions of TRPC6 and CaN in
      the renal tissue were detected by immunohistochemistry, real-time PCR and Western
      blot. RESULTS: The study showed the 24-hour urinary protein increased
      significantly in ADR rats compared with Controls whilst for ADR rats
      hypoalbuminemia, hypercholesterolemia, renal functional lesion and renal
      pathologic changes appeared. The areas and intensities of TRPC6 and CaN expressed
      in the glomerulus and tubulointerstitium of ADR rats increased significantly. The
      expression of TRPC6 mRNA in ADR rats began to increase on the 3rd week and
      persisted to the 7th week, and CaN mRNA increased throughout the period. Protein
      expressions of TRPC6 and CaN in ADR rats were significantly higher than those of
      Controls. FK506 can inhibit CaN activity in the renal tissues and further
      decrease TRPC6 expression and therefore reduce renal damage and proteinuria in a
      dose-dependent manner. CONCLUSIONS: These findings suggested that TRPC6 and CaN
      were up-regulated on mRNA and protein levels in adriamycin-induced rats. FK506
      had a therapeutic effect on the progression of proteinuria and renal damage by
      down-regulating of TRPC6 and CaN in the renal tissues.

PMID- 22865595
TI  - Microalbuminuria is more consistent in the presence of cardiovascular risk
      factors.
AB  - BACKGROUND: The use of microalbuminuria (MAU) to screen for cardiovascular and
      renal risk might be hampered by its intermittent character. This prospective
      observational study assessed traditional risk factors in presumed healthy workers
      with intermittent MAU (IMAU) compared to persistent MAU (PMAU). METHODS: A cohort
      of 239 Belgian workers underwent at least two consecutive occupational check-ups
      with a median time of 12 months. Hypertension (HT) was defined as blood pressure
      >/=140/90 mmHg. Impaired glucose tolerance (IGT) was defined as plasma glucose
      =5.6 mmol/L. MAU was defined as urinary albumin to creatinine ratio of 17-249
      mg/g in men and 25-354 mg/g in women. Workers with IMAU had one positive MAU and
      workers with PMAU had two positive MAU during follow-up. RESULTS: The mean age of
      this mainly male (95%) cohort was 41 +/- 9 years. The prevalence of persistent
      risk factors (HT and/or IGT) was higher in workers with PMAU than without MAU
      (8/12[67%] vs. 55/210[26%], P = .005) while workers with IMAU had no increased
      risk (5/17[29%]). The prevalence of PMAU was higher in workers with vs. without
      persistent risk factors (8/68 = 12% vs. 4/171 = 2%, P = .005) while the
      prevalence of IMAU was the same (5/68 = 7% vs. 12/171 = 7%, P = .93). The
      reproducibility of initial MAU at consecutive visits was higher in workers with
      vs. without persistent risk factors (8/9[89%] vs. 4/11[36%] P = 0.03).
      CONCLUSIONS: The use of MAU as a first step screening strategy in an occupational
      health care setting is hampered by false positives and low sensitivity to
      identify subjects with cardiovascular and renal risk.

PMID- 22865596
TI  - An association between clock genes and clock-controlled cell cycle genes in
      murine colorectal tumors.
AB  - Disruption of circadian machinery appears to be associated with the acceleration
      of tumor development. To evaluate the function of the circadian clock during
      neoplastic transformation, the daily profiles of the core clock genes Per1, Per2,
      Rev-Erbalpha and Bmal1, the clock-controlled gene Dbp and the clock-controlled
      cell cycle genes Wee1, c-Myc and p21 were detected by real-time RT-PCR in
      chemically induced primary colorectal tumors, the surrounding normal tissue and
      in the liver. The circadian rhythmicity of Per1, Per2, Rev-Erbalpha and Dbp was
      significantly reduced in tumor compared with healthy colon and the rhythmicity of
      Bmal1 was completely abolished. Interestingly, the circadian expression of Per1,
      Per2, Rev-Erbalpha and Dbp persisted in the colonic tissue surrounding the tumor
      but the rhythmic expression of Bmal1 was also abolished. Daily profiles of Wee1,
      c-Myc and p21 did not exhibit any rhythmicity either in tumors or in the colon of
      healthy animals. The absence of diurnal rhythmicity of cell cycle genes was
      partially associated with ageing, because young healthy mice showed rhythmicity
      in the core clock genes as well as in the Wee1 and p21. In the liver of tumor
      bearing mice the clock gene rhythms were temporally shifted. The data suggest
      that the circadian regulation is distorted in colonic neoplastic tissue and that
      the gene-specific disruption may be also observed in the non-neoplastic tissues.
      These findings reinforce the role of peripheral circadian clockwork disruption
      for carcinogenesis and tumor progression.

PMID- 22865597
TI  - Nano-hydroxyapatite-coated PEEK implants: a pilot study in rabbit bone.
AB  - Osseointegration of surface-modified polyetheretherketone (PEEK) implants was
      studied in vivo. A total of 18 cylinder-shaped PEEK implants were inserted in the
      femurs of nine New Zealand rabbits; half were coated with nanocrystalline
      hydroxyapatite (nanoHA) and half were uncoated controls. Healing time was 6
      weeks. Samples were retrieved with the implant and surrounding tissue, processed
      to cut and ground sections, and analyzed histomorphometrically. The implant
      surfaces were analyzed with optical interferometry, scanning electron microscopy
      (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy (XPS).
      NanoHA-coated PEEK surfaces had lower height deviation (Sa) than controls [mean
      +/- SD: 0.41 MUm (+/- 0.14) vs. 0.96 MUm (+/- 0.28)]. SEM images showed the
      nanoHA crystals as a thin layer on the polymer surface. XPS analysis of the
      coated implants showed a Ca/P ratio of 1.67. Histomorphometry indicated that the
      nanoHA-coated implants had more bone-to-implant contact [16% (+/- 4.7) vs. 13%
      (+/- 9.3)] and more bone area [52% (+/- 9.5) vs. 45% (+/- 11.9)]. We found no
      difference between smooth nanoHA-coated cylinder-shaped PEEK implants and
      uncoated controls. However, higher mean bone-to-implant contact indicated better
      osseointegration in the coated implants than in the uncoated controls. The large
      number of lost implants was interpreted as a lack of primary stability due to
      implant design.

PMID- 22865598
TI  - Dichotomising continuous data while retaining statistical power using a
      distributional approach.
AB  - Dichotomisation of continuous data is known to be hugely problematic because
      information is lost, power is reduced and relationships may be obscured or
      changed. However, not only are differences in means difficult for clinicians to
      interpret, but thresholds also occur in many areas of medical practice and cannot
      be ignored. In recognition of both the problems of dichotomisation and the ways
      in which it may be useful clinically, we have used a distributional approach to
      derive a difference in proportions with a 95% CI that retains the precision and
      the power of the CI for the equivalent difference in means. In this way, we
      propose a dual approach that analyses continuous data using both means and
      proportions to replace dichotomisation alone and that may be useful in certain
      situations. We illustrate this work with examples and simulations that show good
      performance of the parametric approach under standard distributional assumptions
      from our own research and from the literature.

PMID- 22865599
TI  - The impact of antioxidant supplements and endurance exercise on genes of the
      carbohydrate and lipid metabolism in skeletal muscle of mice.
AB  - To ascertain whether reactive oxygen species (ROS) contribute to training-induced
      adaptation of skeletal muscle, we administered ROS-scavenging antioxidants (AOX;
      140 mg/l of ascorbic acid, 12 mg/l of coenzyme Q10 and 1% N-acetyl-cysteine) via
      drinking water to 16 C57BL/6 mice. Sixteen other mice received unadulterated tap
      water (CON). One cohort of both groups (CON(EXE) and AOX(EXE) ) was subjected to
      treadmill exercise for 4 weeks (16-26 m/min, incline of 5 degrees -10 degrees ).
      The other two cohorts (CON(SED) and AOX(SED) ) remained sedentary. In skeletal
      muscles of the AOX(EXE) mice, GSSG and the expression levels of SOD-1 and PRDX-6
      were significantly lower than those in the CON(EXE) mice after training,
      suggesting disturbance of ROS levels. The peak power related to the body weight
      and citrate synthase activity was not significantly influenced in mice receiving
      AOX. Supplementation with AOX significantly altered the mRNA levels of the
      exercise-sensitive genes HK-II, GLUT-4 and SREBF-1c and the regulator gene PGC
      1alpha but not G6PDH, glycogenin, FABP-3, MCAD and CD36 in skeletal muscle.
      Although the administration of AOX during endurance exercise alters the
      expression of particular genes of the ROS metabolism, it does not influence peak
      power or generally shift the metabolism, but it modulates the expression of
      specific genes of the carbohydrate and lipid metabolism and PGC-1alpha within
      murine skeletal muscle.

PMID- 22865600
TI  - Solar fuels: visible-light-driven generation of dihydrogen at p-type silicon
      electrocatalysed by molybdenum hydrides.
AB  - We show that a robust molybdenum hydride system can sustain photoelectrocatalysis
      of a hydrogen evolution reaction at boron-doped, hydrogen-terminated, p-type
      silicon. The photovoltage for the system is about 600-650 mV and the current
      densities, which can be sustained at the photocathode in non-catalytic and
      catalytic regimes, are similar to those at a photoinert vitreous carbon
      electrode. The kinetics of electrocatalysed hydrogen evolution at the
      photocathode are also very similar to those measured at vitreous carbon-evidently
      visible light does not significantly perturb the catalytic mechanism.
      Importantly, we show that the doped (1-10 Omega cm) p-type Si can function
      perfectly well in the dark as an ohmic conductor and this has allowed direct
      comparison of the cyclic voltammetric behaviour of the response of the system
      under dark and illuminated conditions at the same electrode. The p-type Si we
      have employed optimally harvests light energy in the 600-700 nm region and with
      37 mW cm(-2)  illumination in this range; the light to electrochemical energy
      conversion is estimated to be 2.8 %. The current yield of hydrogen under broad
      tungsten halide lamp illumination at 90 mW cm(-2)  is (91+/-5) % with a
      corresponding chemical yield of (98+/-5) %.

PMID- 22865601
TI  - Physicochemical properties and cellular toxicity of (poly)aminoalkoxysilanes
      functionalized ZnO quantum dots.
AB  - Luminescent ZnO nanocrystals were synthesized by basic hydrolysis of Zn(OAc)(2)
      in the presence of oleic acid and then functionalized with
      (poly)aminotrimethoxysilanes in the presence of tetramethylammonium hydroxide to
      render the QDs water-dispersible. The highest photoluminescence quantum yield
      (17%) was achieved using N(1)-(2-aminoethyl)-N(2)-[3-(trimethoxysilyl)propyl]-1,2
      ethanediamine as surface ligand. Transmission electron microscopy and powder x
      ray diffraction showed highly crystalline materials with a ZnO nanoparticle
      diameter of about 4 nm. The cytotoxicity of the different siloxane-capped ZnO QDs
      towards growing  Escherichia coli bacterial cells was evaluated in MOPS-minimal
      medium. Although concentrations of 5 mM in QDs caused a complete growth arrest in
      E. coli, siloxane-capped ZnO QDs appeared weakly toxic at lower doses (0.5 or 1
      mM). The concentration of bioavailable Zn (2+) ions leaked from ZnO QDs was
      evaluated using the biosensor bacteria  Cupriavidus metallidurans AE1433. The
      results obtained clearly demonstrate that concentrations of bioavailable Zn(2+)
      are too low to explain the inhibitory effects of the ZnO QDs against bacteria
      cells at 1 mM and that the siloxane shell prevents ZnO QDs from dissolution
      contrary to uncapped ZnO nanoparticles. Because of their low cytotoxicity, good
      biocompatibility, low cost and large number of functional amine end groups, which
      makes them easy to tailor for end-user purposes, siloxane-capped ZnO QDs offer a
      high potential as fluorescent probes and as biosensors.

PMID- 22865602
TI  - In reference to Cost-effective dental protection during rigid endoscopy.

PMID- 22865603
TI  - Evaluation of weight loss and adipocytokines levels after two hypocaloric diets
      with different macronutrient distribution in obese subjects with rs9939609 gene
      variant.
AB  - BACKGROUND: Common polymorphisms of the fat mass and obesity associated gene
      (FTO) have been linked to obesity in some populations. One of these genetic
      variants (rs9939609) has been related to an increased risk of obesity. OBJECTIVE:
      Our aim was to evaluate weight loss and adipocytokine levels after two
      hypocaloric diets with different macronutrient distribution in obese subjects
      with RS9939609 gene variant. DESIGN: 305 obese patients were enrolled in a
      prospective way. In the basal visit, patients were randomly allocated during 3
      months to low carbohydrates and low fat. RESULTS: After treatment with both diets
      and in both genotypes, weight, fat mass, waist circumference and systolic blood
      pressures decreased. With the diet type I and in TT genotype, insulin (-6.6 +/-
      9.8 IU/L) and homeostasis model assessment (-2.9 +/- 6.1 units) decreased. With
      the diet type II and in both genotypes (wild and mutant type), insulin (-5.2 +/-
      6.1 vs. -3.8 +/- 6.1 IU/L; p < 0.05) and homeostasis model assessment (-2.4 +/-
      4.8 vs. -1.1 +/- 3.8 kg; p < 0.05) decreased. In the A allele group, a
      significant decrease was detected in total cholesterol levels (-11.5 +/- 20.1
      mg/dL), low density lipoprotein cholesterol levels (-13.2 +/- 20.9 mg/dL) and c
      reactive protein levels (-1.3 +/- 3.8 mg/dL) secondary to weight loss after
      treatment with diet II. The decrease of leptin levels was higher in mutant type
      group than wild type group with low fat diet (-10.3 +/- 36.1 vs. -28.6 +/- 53.7
      ng/mL; p < 0.05). CONCLUSION: Metabolic improvement secondary to weight loss was
      better in A carriers with a low fat hypocaloric diet.

PMID- 22865604
TI  - Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA
      synthesis in neurons.
AB  - Mutations in the gene encoding the methyl-CpG-binding protein MECP2 are the major
      cause of Rett syndrome, an autism spectrum disorder mainly affecting young
      females. MeCP2 is an abundant chromatin-associated protein, but how and when its
      absence begins to alter brain function is still far from clear. Using a stem cell
      based system allowing the synchronous differentiation of neuronal progenitors, we
      found that in the absence of MeCP2, the size of neuronal nuclei fails to increase
      at normal rates during differentiation. This is accompanied by a marked decrease
      in the rate of ribonucleotide incorporation, indicating an early role of MeCP2 in
      regulating total gene transcription, not restricted to selected mRNAs. We also
      found that the levels of brain-derived neurotrophic factor (BDNF) were decreased
      in mutant neurons, while those of the presynaptic protein synaptophysin increased
      at similar rates in wild-type and mutant neurons. By contrast, nuclear size,
      transcription rates, and BDNF levels remained unchanged in astrocytes lacking
      MeCP2. Re-expressing MeCP2 in mutant neurons rescued the nuclear size phenotype
      as well as BDNF levels. These results reveal a new role of MeCP2 in regulating
      overall RNA synthesis in neurons during the course of their maturation, in line
      with recent findings indicating a reduced nucleolar size in neurons of the
      developing brain of mice lacking Mecp2.

PMID- 22865605
TI  - One-step synthesis of thermosensitive nanogels based on highly cross-linked
      poly(ionic liquid)s.
AB  - A gel for all seasons: Thermosensitive nanogels based on highly cross-linked
      poly(ionic liquid)s (CLPNs) were prepared in one step by the copolymerization of
      imidazolium-based monomers with cross-linkers in selective solvents. Reversible
      nanogel-macrogel transitions of CLPNs in methanol could be achieved by changing
      the temperature.

PMID- 22865606
TI  - Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic
      profile in human plasma following coffee consumption.
AB  - SCOPE: This study reports the 24 h human plasma pharmacokinetics of 3,4
      dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and
      the membrane transport characteristics of certain dimethoxycinnamic acid
      derivatives, as present in coffee. METHODS AND RESULTS: Eight healthy human
      volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of
      commercially available coffee. Plasma samples were collected over 24 h and
      analyzed by HPLC-MS(2) . Investigation of the mechanism of absorption and
      metabolism was performed using an intestinal Caco-2 cell model. For the first
      time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone.
      The time to reach the C(max)  value of approximately 0.5 MUM was rapid, T(max)  =
      30 min, and showed an additional peak at 2-4 h for several subjects. In contrast,
      smaller amounts of dimethoxy-dihydrocinnamic acid (C(max)  ~ 0.1 MUM) peaked
      between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid
      was preferentially transported in the free form by passive diffusion, and a small
      amount of dimethoxycinnamoylquinic acid hydrolysis was observed. CONCLUSION:
      These findings show that dimethoxycinnamic acid, previously identified in plasma
      after coffee consumption, was rapidly absorbed in the free form most likely by
      passive diffusion in the upper gastrointestinal tract.

PMID- 22865608
TI  - MUTYH c.933+3A>C, associated with a severely impaired gene expression, is the
      first Italian founder mutation in MUTYH-Associated Polyposis.
AB  - MUTYH variants are differently distributed in geographical areas of the world. In
      MUTYH-associated polyposis (MAP) patients from North-Eastern Italy, c.933+3A>C
      (IVS10+3A>C), a transversion causing an aberrant splicing process, accounts for
      nearly 1/5 of all mutations. The aim of this study was to verify whether its high
      frequency in North-Eastern Italy is due to a founder effect and to clarify its
      impact on MUTYH transcripts and protein. Haplotype analysis and age estimate
      performed on members of eleven Italian MAP families and cancer-free controls
      provided evidence that c.933+3A>C is a founder mutation originated about 83
      generations ago. In addition, the Italian haplotype associated with the
      c.933+3A>C was also found in German families segregating the same mutation,
      indicating it had a common origin in Western Europe. Altogether c.933+3A>C and
      the two common Caucasian mutations p.Tyr179Cys and p.Gly396Asp represent about
      60% of MUTYH alterations in MAP patients from North-Eastern Italy, suggesting the
      opportunity to perform targeted molecular screening for these variants in the
      diagnostic setting. Expression analyses performed on lymphoblastoid cell lines
      supported the notion that MUTYH c.933+3A>C alters splicing causing the synthesis
      of a non functional protein. However, some primary transcripts escape aberrant
      splicing, producing traces of full-length transcript and wild-type protein in a
      homozygote; this is in agreement with clinical findings that suggest a relatively
      mild phenotypic effect for this mutation. Overall, these data, that demonstrate a
      founder effect and further elucidate the splicing alterations caused by the MUTYH
      c.933+3A>C mutation, have important implications for genetic counseling and
      molecular diagnosis of MAP.

PMID- 22865609
TI  - An innovative stand-alone bioreactor for the highly reproducible transfer of
      cyclic mechanical stretch to stem cells cultured in a 3D scaffold.
AB  - Much evidence in the literature demonstrates the effect of cyclic mechanical
      stretch in maintaining, or addressing, a muscle phenotype. Such results were
      obtained using several technical approaches, useful for the experimental
      collection of proofs of principle but probably unsuitable for application in
      clinical regenerative medicine. Here we aimed to design a reliable innovative
      bioreactor, acting as a stand-alone cell culture incubator, easy to operate and
      effective in addressing mesenchymal stem cells (MSCs) seeded onto a 3D
      bioreabsorbable scaffold, towards a muscle phenotype via the transfer of a
      controlled and highly-reproducible cyclic deformation. Electron microscopy,
      immunohistochemistry and biochemical analysis of the obtained pseudotissue
      constructs showed that cells 'trained' over 1 week: (a) displayed multilayer
      organization and invaded the 3D mesh of the scaffold; and (b) expressed typical
      markers of muscle cells. This effect was due only to physical stimulation of the
      cells, without the need of any other chemical or genetic manipulation. This
      device is thus proposed as a prototypal instrument to obtain pseudotissue
      constructs to test in cardiovascular regenerative medicine, using good
      manufacturing procedures.

PMID- 22865610
TI  - A simple method for estimating the odds ratio in matched case-control studies
      with incomplete paired data.
AB  - Paired data from matched case-control studies are commonly used to estimate the
      association between the exposure to a risk factor and the occurrence of a
      disease. The odds ratio is typically used to quantify this association.
      Difficulties in estimating the true odds ratio with matched pairs arise, however,
      when the exposure status is unknown for one of the individuals in one or more
      pairs. In this article, we propose a simple method for estimating the odds ratio
      when the sample consists of a combination of complete and incomplete matched
      pairs; that is, some of the pairs have exposure data for both the case and the
      control, some of the pairs have exposure data just for the case, and the
      remaining pairs have exposure data just for the control. This method uses a
      weighted average of the odds ratio estimator that is most commonly used when the
      sample consists entirely of complete paired observations and the odds ratio
      estimator that is most commonly used when the sample consists entirely of
      unpaired observations. The proposed estimator has simple closed-form expressions
      for the estimate of the odds ratio and its approximate variance. We compare our
      method to existing methods via simulation and show that our method is comparable
      to or better than the other methods in terms of bias, mean squared error, and
      confidence interval coverage probability and width.

PMID- 22865611
TI  - The involvement of AQP1 in heart oedema induced by global myocardial ischemia.
AB  - Aquaporin-1 (AQP1) is a member of aquaporin family that was previously proven to
      be involved in myocardial dysfunction; however, the role of AQP1 in myocardial
      stunning is less clear. To determine the change of AQP1 expression level in the
      heart and its effect on oedema after global myocardial ischemia, 40 adult goats
      underwent cardiopulmonary bypass (CPB) with an aortic cross-clamp time of 2 h and
      total bypass time of 6, 12, 24, 48 and 72 h followed by subsequent reperfusion.
      AQP1 function of eight goats was inhibited by HgCl(2) during the 24 h on CPB. All
      groups were compared with eight sham bypass control goats. Myocardial water
      content was measured, and the APQ1 mRNA and protein levels were detected by RT
      PCR and immunoblotting, respectively. The results showed that the degree of
      myocardial oedema increased significantly at 6, 12, 24 and 48 h of reperfusion
      after CPB as compared with the control and recovered at 72 h of subsequent
      reperfusion. Expression levels of AQP1 mRNA and protein began to increase at 12 h
      and peaked at 24 h of CPB following reperfusion. Furthermore, myocardial oedema
      was reduced in the HgCl(2) group compared with the time-matched CPB and control
      groups. These data suggested that AQP1 expression increases in CPB and AQP1 plays
      an important role in myocardial oedema during CPB.

PMID- 22865612
TI  - A molybdenum disulfide/carbon nanotube heterogeneous complementary inverter.
AB  - We report a simple, bottom-up/top-down approach for integrating drastically
      different nanoscale building blocks to form a heterogeneous complementary
      inverter circuit based on layered molybdenum disulfide and carbon nanotube (CNT)
      bundles. The fabricated CNT/MoS(2) inverter is composed of n-type molybdenum
      disulfide (MOS(2)) and p-type CNT transistors, with a high voltage gain of 1.3.
      The CNT channels are fabricated using directed assembly while the layered
      molybdenum disulfide channels are fabricated by mechanical exfoliation. This
      bottom-up fabrication approach for integrating various nanoscale elements with
      unique characteristics provides an alternative cost-effective methodology to
      complementary metal-oxide-semiconductors, laying the foundation for the
      realization of high performance logic circuits.

PMID- 22865613
TI  - Evaluation of adult Pott's puffy tumor: our five cases and 27 literature cases.
AB  - OBJECTIVES/HYPOTHESIS: Pott's puffy tumor (PPT) is defined as one or more
      subperiosteal abscesses of the frontal bone based on osteomyelitis. PPT is
      observed predominantly in the adolescent age group and rarely in adults. Some
      parameters affecting prognosis and an appropriate surgical approach for
      antecedent frontal sinusitis have not been elucidated due to the rarity of
      patients with adult PPT. STUDY DESIGN: Retrospective patient record and
      literature study. METHODS: Five patients from our cohort and 27 patients
      identified in a literature search formed the study group. RESULTS: The incidence
      rate of intracranial complications was lower than in previous reports at 29.0%.
      There was no correlation between the incidence rate of intracranial complications
      and each patient's parameters. It was indicated that the department first
      consulted by the patients was possibly related to the initial diagnosis and the
      incidence rate of intracranial complications. CONCLUSIONS: Although the incidence
      rate of major complications is lower than in children and later than in earlier
      published adult cases, patients are still at high risk of serious intracranial
      complications. Early diagnosis and adequate treatment may contribute to reducing
      the incidence rate.

PMID- 22865614
TI  - Nucleation-based prediction of the protein folding rate and its correlation with
      the folding nucleus size.
AB  - The problem of protein self-organization is in the focus of current molecular
      biology studies. Although the general principles are understood, many details
      remain unclear. Specifically, protein folding rates are of interest because they
      dictate the rate of protein aggregation which underlies many human diseases. Here
      we offer predictions of protein folding rates and their correlation with folding
      nucleus sizes. We calculated free energies of the transition state and sizes of
      folding nuclei for 84 proteins and peptides whose other parameters were measured
      at the point of thermodynamic equilibrium between their unfolded and native
      states. We used the dynamic programming method where each residue was considered
      to be either as folded as in its native state or completely disordered. The
      calculated and measured folding rates showed a good correlation at the
      temperature mid-transition point (the correlation coefficient was 0.75). Also, we
      pioneered in demonstrating a moderate (-0.57) correlation coefficient between the
      calculated sizes of folding nuclei and the folding rates. Predictions made by
      different methods were compared. The established good correlation between the
      estimated free energy barrier and the experimentally found folding rate of each
      studied protein/peptide indicates that our model gives reliable results for the
      considered data set.

PMID- 22865615
TI  - Activation of Notch signaling during ex vivo expansion maintains donor muscle
      cell engraftment.
AB  - Transplantation of myogenic stem cells possesses great potential for long-term
      repair of dystrophic muscle. However, a single donor muscle biopsy is unlikely to
      provide enough cells to effectively transplant the muscle mass of a patient
      affected by muscular dystrophy. Expansion of cells ex vivo using traditional
      culture techniques significantly reduces engraftment potential. We hypothesized
      that activation of Notch signaling during ex vivo expansion would maintain donor
      cell engraftment potential. In this study, we expanded freshly isolated canine
      muscle-derived cells on tissue culture plates coated with Delta-1(ext) -IgG to
      activate Notch signaling or with human IgG as a control. A model of canine-to
      murine xenotransplantation was used to quantitatively compare canine muscle cell
      engraftment and determine whether engrafted donor cells could function as
      satellite cells in vivo. We show that Delta-1(ext) -IgG inhibited differentiation
      of canine muscle-derived cells and increased the level of genes normally
      expressed in myogenic precursors. Moreover, cells expanded on Delta-1(ext) -IgG
      resulted in a significant increase in the number of donor-derived fibers, as
      compared to cells expanded on human IgG, reaching engraftment levels similar to
      freshly isolated cells. Importantly, cells expanded on Delta-1(ext) -IgG
      engrafted to the recipient satellite cell niche and contributed to further
      regeneration. A similar strategy of expanding human muscle-derived cells on Notch
      ligand might facilitate engraftment and muscle regeneration for patients affected
      with muscular dystrophy.

PMID- 22865616
TI  - A fast and noise-resilient approach to detect rare-variant associations with deep
      sequencing data for complex disorders.
AB  - Next generation sequencing technology has enabled the paradigm shift in genetic
      association studies from the common disease/common variant to common disease/rare
      variant hypothesis. Analyzing individual rare variants is known to be
      underpowered; therefore association methods have been developed that aggregate
      variants across a genetic region, which for exome sequencing is usually a gene.
      The foreseeable widespread use of whole genome sequencing poses new challenges in
      statistical analysis. It calls for new rare-variant association methods that are
      statistically powerful, robust against high levels of noise due to inclusion of
      noncausal variants, and yet computationally efficient. We propose a simple and
      powerful statistic that combines the disease-associated P-values of individual
      variants using a weight that is the inverse of the expected standard deviation of
      the allele frequencies under the null. This approach, dubbed as Sigma-P method,
      is extremely robust to the inclusion of a high proportion of noncausal variants
      and is also powerful when both detrimental and protective variants are present
      within a genetic region. The performance of the Sigma-P method was tested using
      simulated data based on realistic population demographic and disease models and
      its power was compared to several previously published methods. The results
      demonstrate that this method generally outperforms other rare-variant association
      methods over a wide range of models. Additionally, sequence data on the ANGPTL
      family of genes from the Dallas Heart Study were tested for associations with
      nine metabolic traits and both known and novel putative associations were
      uncovered using the Sigma-P method.

PMID- 22865618
TI  - A reply to Weitzer.
AB  - This is a reply to Ronald Weitzer's criticisms of anti-pornography feminism. I
      argue that Weitzer has misrepresented the anti-pornography feminist position
      reflected in the work of Gail Dines.

PMID- 22865617
TI  - Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood
      disorders in the United States.
AB  - Estimates of 12-month and lifetime prevalence and of lifetime morbid risk (LMR)
      of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      Text Revision (DSM-IV-TR) anxiety and mood disorders are presented based on US
      epidemiological surveys among people aged 13+. The presentation is designed for
      use in the upcoming DSM-5 manual to provide more coherent estimates than would
      otherwise be available. Prevalence estimates are presented for the age groups
      proposed by DSM-5 workgroups as the most useful to consider for policy planning
      purposes. The LMR/12-month prevalence estimates ranked by frequency are as
      follows: major depressive episode: 29.9%/8.6%; specific phobia: 18.4/12.1%;
      social phobia: 13.0/7.4%; post-traumatic stress disorder: 10.1/3.7%; generalized
      anxiety disorder: 9.0/2.0%; separation anxiety disorder: 8.7/1.2%; panic
      disorder: 6.8%/2.4%; bipolar disorder: 4.1/1.8%; agoraphobia: 3.7/1.7%; obsessive
      compulsive disorder: 2.7/1.2. Four broad patterns of results are most noteworthy:
      first, that the most common (lifetime prevalence/morbid risk) lifetime anxiety
      mood disorders in the United States are major depression (16.6/29.9%), specific
      phobia (15.6/18.4%), and social phobia (10.7/13.0%) and the least common are
      agoraphobia (2.5/3.7%) and obsessive-compulsive disorder (2.3/2.7%); second, that
      the anxiety-mood disorders with the earlier median ages-of-onset are phobias and
      separation anxiety disorder (ages 15-17) and those with the latest are panic
      disorder, major depression, and generalized anxiety disorder (ages 23-30); third,
      that LMR is considerably higher than lifetime prevalence for most anxiety-mood
      disorders, although the magnitude of this difference is much higher for disorders
      with later than earlier ages-of-onset; and fourth, that the ratio of 12-month to
      lifetime prevalence, roughly characterizing persistence, varies meaningfully in
      ways consistent with independent evidence about differential persistence of these
      disorders.

PMID- 22865619
TI  - The myth of objectivity: a reply to Weitzer.
AB  - In this article, the editor of Everyday Pornography offers a response to Ronald
      Weitzer's 2011 review of that book, addressing questions about objectivity, the
      framing of pornography as violence against women, the role of women's testimony
      in debates about pornography, and research on porn's consumers.

PMID- 22865620
TI  - A feminist response to Weitzer.
AB  - In his review of my book Pornland: How Porn has Hijacked our Sexuality, Ronald
      Weitzer claims that anti-porn feminists are incapable of objective, rigorous
      research because they operate within the "oppression paradigm," which he defines
      as "a perspective that depicts all types of sex work as exploitive, violent, and
      perpetuating gender inequality." (VAW, 2011, 666). This article argues that while
      anti-porn feminists do indeed see pornography as exploitive, such a position is
      rooted in the rigorous theories and methods of cultural studies developed by
      critical media scholars such as Stuart Hall and Antonio Gramsci. Pornland applies
      a cultural studies approach by exploring how porn images are part of a wider
      system of sexist representations that legitimize and normalize the economic,
      political and legal oppression of women.

PMID- 22865621
TI  - Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast
      agents.
AB  - Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles
      (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion
      at 37  degrees C and 20 MHz). This high relaxation rate is due to efficient Gd
      loading, reduced tumbling of the Gd complex, and the hydrogel nature of the
      nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode
      contrast agent was studied in C6 cells.

PMID- 22865622
TI  - Synthesis of trans-disubstituted alkenes by cobalt-catalyzed reductive coupling
      of terminal alkynes with activated alkenes.
AB  - A cobalt-catalyzed reductive coupling of terminal alkynes, RC=CH, with activated
      alkenes, R'CH=CH(2), in the presence of zinc and water to give functionalized
      trans-disubstituted alkenes, RCH=CHCH(2)CH(2)R', is described. A variety of
      aromatic terminal alkynes underwent reductive coupling with activated alkenes
      including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of
      a CoCl(2)/P(OMe)(3)/Zn catalyst system to afford 1,2-trans-disubstituted alkenes
      with high regio- and stereoselectivity. Similarly, aliphatic terminal alkynes
      also efficiently participated in the coupling reaction with acrylates, enones,
      and vinyl sulfone, in the presence of the CoCl(2)/P(OPh)(3)/Zn system providing a
      mixture of 1,2-trans- and 1,1-disubstituted functionalized terminal alkene
      products in high yields. The scope of the reaction was also extended by the
      coupling of 1,3-enynes and acetylene gas with alkenes. Furthermore, a phosphine
      free cobalt-catalyzed reductive coupling of terminal alkynes with enones,
      affording 1,2-trans-disubstituted alkenes as the major products in a high
      regioisomeric ratio, is demonstrated. In the reactions, less expensive and air
      stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source
      (water) were used. A possible reaction mechanism involving a cobaltacyclopentene
      as the key intermediate is proposed.

PMID- 22865623
TI  - Phenazine content in the cystic fibrosis respiratory tract negatively correlates
      with lung function and microbial complexity.
AB  - Although much is known about how virulence factors affect pathogens and host
      tissues in vitro, far less is understood about their dynamics in vivo. As a step
      toward characterizing the chemistry of infected environments, we measured
      phenazine abundance in the lungs of patients with cystic fibrosis (CF).
      Phenazines are redox-active small molecules produced by Pseudomonas aeruginosa
      that damage host epithelia, curb the growth of competing organisms, and play
      physiologically important roles in the cells that produce them. Here, we quantify
      phenazines within expectorated sputum, characterize the P. aeruginosa populations
      responsible for phenazine production, and assess their relationship to CF lung
      microflora. Chemical analyses of expectorated sputum showed that the
      concentrations of two phenazines, namely, pyocyanin (PYO) and phenazine-1
      carboxylic acid (PCA), were negatively correlated (rho = -0.68 and -0.57,
      respectively) with lung function. Furthermore, the highest phenazine
      concentrations were found in patients whose pulmonary function showed the
      greatest rates of decline. The constituent P. aeruginosa populations within each
      patient showed diverse capacities for phenazine production. Early during
      infection, individual isolates produced more PYO than later during infection.
      However, total PYO concentrations in sputum at any given stage correlated well
      with the average production by the total P. aeruginosa population. Finally,
      bacterial community complexity was negatively correlated with phenazine
      concentrations and declines in lung function, suggesting a link to the refinement
      of the overall microbial population. Together, these data demonstrate that
      phenazines negatively correlate with CF disease states in ways that were
      previously unknown, and underscore the importance of defining in vivo
      environmental parameters to better predict clinical outcomes of infections.

PMID- 22865624
TI  - Role of CXC chemokine receptor-2 in a murine model of bronchopulmonary dysplasia.
AB  - The contribution of neutrophils and CXC chemokines to the pathogenesis of
      bronchopulmonary dysplasia is not well defined. The transgenic expression of IL
      1beta in the pulmonary epithelium causes lung inflammation and disrupts alveolar
      development in infant mice. To study the hypothesis that CXC chemokine receptor-2
      (CXCR2) is a mediator of inflammatory lung injury, we compared lung development
      in IL-1beta-expressing mice with wild-type (IL-1beta/CXCR2(+/+)) or null (IL
      1beta/CXCR2(-/-)) CXCR2 loci. CXCR2 deficiency abolished the transmigration of
      neutrophils into the alveolar lumen in IL-1beta-expressing mice, but did not
      alter the number of neutrophils in the parenchyma. The deletion of CXCR2
      increased the alveolar chord length and reduced the survival of mice when IL
      1beta was expressed from the pseudoglandular to the alveolar stages. The
      capillary configuration was highly abnormal in both IL-1beta/CXCR2(+/+) and IL
      1beta/CXCR2(-/-) lungs, but in very different ways. The cellular area of the
      parenchyma and the total capillary area of IL-1beta/CXCR2(+/+) and IL
      1beta/CXCR2(-/-) mice were smaller than those of control/CXCR2(+/+) and
      control/CXCR2(-/-) mice, but the ratio of capillary area to cellular area was
      similar in all four genotypes. When IL-1beta was expressed during the saccular
      stage, IL-1beta/CXCR2(-/-) mice had smaller alveolar chord lengths and better
      survival than did IL-1beta/CXCR2(+/+) mice. Independent of the timing of IL-1beta
      expression, IL-1beta increased alveolar septal thickness in mice with wild-type
      CXCR2 loci, but not in CXCR2 null mice. Depending on the developmental stage at
      the time of the inflammatory insult, inhibition of the CXCR2 pathway may exert
      opposite effects on alveolar septation in the neonatal lung.

PMID- 22865625
TI  - Steroids and beta2-agonists regulate hyaluronan metabolism in asthmatic airway
      smooth muscle cells.
AB  - Glycosaminoglycans (GAGs), especially hyaluronic acid (HA), regulate tissue
      flexibility, cell motility, and inflammation. Airway smooth muscle cells (ASMCs)
      of patients with asthma exhibit abnormal HA metabolism, which contributes to
      inflammation and remodeling. Here, we investigated the effects of glucocorticoids
      and long-acting beta(2)-agonists (LABAs) on GAG synthesis and HA metabolism by
      human primary ASMCs. ASMCs were isolated from airway specimens of 10 patients
      without asthma and 11 patients with asthma. ASMCs were incubated with
      glucocorticoids, LABAs, or their combination, as well as with their specific
      receptor antagonists. Secreted and deposited total GAGs were measured by [(3)H]
      glucosamine incorporation. The expression of specific GAGs was determined by
      ELISA and electrophoresis. The expression of HA synthases (HAS), of
      hyaluronidases (HYALs), and of the HA receptor CD44 was determined by RT-PCR,
      immunoblotting in cell cultures, and immunohistochemistry in tissue sections of
      asthmatic lungs. In serum-activated asthmatic ASMCs, glucocorticoids and LABAs
      significantly inhibited the increased secretion and deposition of total GAGs, but
      they stimulated secreted and deposited HA of high molecular mass. This effect was
      attributed to increased mRNA and protein expression of HAS-1 and to the reduced
      expression of HYAL-1. Furthermore, drug treatment stimulated the expression of
      CD44 receptors in asthmatic ASMCs. These effects of the drugs were eliminated by
      their respective receptor inhibitors. Our findings indicate that the combination
      of glucocorticoids with LABAs counteracts the pathologic degradation of HA, and
      thereby may reduce the proinflammatory potential of asthmatic ASMCs.

PMID- 22865626
TI  - Two-stage designs for Phase 2 dose-finding trials.
AB  - We propose a Bayesian adaptive two-stage design for the efficient estimation of
      the maximum dose or the minimum effective dose in a dose-finding trial. The new
      design allocates subjects in stage two according to the posterior distribution of
      the target dose location. Simulations show that the proposed two-stage design is
      superior to equal allocation and to a two-stage strategy where only one dose is
      left in the second stage.

PMID- 22865627
TI  - Effect of exercise intensity and duration on capillary glucose responses in
      pregnant women at low and high risk for gestational diabetes.
AB  - BACKGROUND: Exercise may influence glucose metabolism during pregnancy. We
      examined the effect of exercise intensity and duration on capillary glucose
      responses in pregnant women at low and high risk for gestational diabetes
      mellitus (GDM) who followed a modified GDM meal plan. METHODS: Randomization
      occurred at study entry (16-20 weeks' gestation) into a low-intensity [30% heart
      rate reserve, low risk-30%I, n = 12; high risk-30%I, n = 11] or vigorous
      intensity (70% heart rate reserve, low risk-70%I, n = 12; R-70%I, n = 11)
      exercise program with similar nutritional control. Exercise consisted of walking
      three to four times a week, gradually increasing time from 25 to 40 min/session.
      Free-living capillary glucose concentrations were measured once a week pre
      exercise and post-exercise. RESULTS: Capillary glucose responses to exercise were
      strongly influenced by an interaction between GDM risk, exercise duration and
      exercise intensity (p = 0.006). Decreases in glucose concentrations were observed
      after 25 (4 +/- 13%), 35 (21 +/- 12%) and 40 min (15 +/- 18%) of walking in high
      risk-30%I women, with the most noticeable decline after 35 and 40 min. In the
      high risk-70%I, glucose concentrations decreased significantly only after 25 (22
      +/- 14%) and 35 min (7 +/- 23%) and increasing the exercise time attenuated
      glucose concentrations decline. In low risk women, regardless of exercise
      intensity and duration, decreases in glucose concentrations were significant and
      similar. CONCLUSION: To achieve the best decline in glucose concentrations,
      pregnant women who follow a modified GDM meal plan should walk for 25 min/session
      at vigorous intensity or for 35-40 min/session at low intensity if they are at
      risk for GDM and for at least 25 min at either low or vigorous intensity if they
      are at low risk for GDM.

PMID- 22865628
TI  - Bleaching response of Symbiodinium (zooxanthellae): determination by flow
      cytometry.
AB  - Coral bleaching is of increasing concern to reef management and stakeholders.
      Thus far, quantification of coral bleaching tends to be heavily reliant on the
      enumeration of zooxanthellae, with less emphasis on assessment of photosynthetic
      or physiological condition, these being often assessed separately by techniques
      such as liquid chromatography. Traditional methods of enumeration using
      microscopy are time consuming, subjected to low precision and great observer
      error. In this study, we presented a method for the distinction of physoiological
      condition and rapid enumeration of zooxanthellae using flow cytometry (FCM).
      Microscopy verified that healthy looking/live versus damaged/dead zooxanthellae
      could be reliably and objectively distinguished and counted by FCM on the basis
      of red and green fluorescence and light scatter. Excellent correlations were also
      determined between FCM and microscopy estimates of cell concentrations of fresh
      zooxanthellae isolates from Pocillopora damicornis. The relative intensities of
      chlorophyll and beta-carotene fluorescences were shown to be important in
      understanding the results of increased cell counts in freshly isolated
      zooxanthellae experimentally exposed to high temperatures (34, 36, and 38 degrees
      C) over 24 h, with ambient temperature (29 degrees C) used as controls. The
      ability to simultaneously identify and enumerate subpopulations of different
      physiological states in the same sample provides an enormous advantage in not
      just determining bleaching responses, but elucidating adaptive response and
      mechanisms for tolerance. Therefore, this approach might provide a rapid,
      convenient, and reproducible methodology for climate change studies and reef
      management programs.

PMID- 22865629
TI  - Visualizing the three-dimensional mesoscopic structure of dermal tissues.
AB  - Thorough knowledge of dermal tissue structure in three dimensions is not only a
      prerequisite for understanding the relationship between cells and their
      extracellular matrix, but also provides a basis for understanding of wound
      healing and scar formation for designing the ideal scaffold for skin tissue
      engineering. Here, we show for the first time the visualization of the three
      dimensional (3D) structure of dermal tissue by phase-contrast microtomography
      (MUCT) with third-generation synchrotron radiation (SR). Compared with irregular
      dermal tissue (such as scar tissue), the normal dermal tissues were found to
      consist of a network of elliptically shaped regions containing a web of fibre
      bundles. The bundles, composed of fibres, were found to be orientated along
      specific directions, indicative of helical weaving. A regular array of dentate
      structure was shown on the fibres. The results showed that phase-contrast MUCT
      with SR had a distinct advantage in accurately viewing the 3D microstructure of
      dermal tissues.

PMID- 22865630
TI  - Longitudinal study of children with unilateral hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: Children with unilateral hearing loss (UHL) have been
      found to have lower language scores, and increased rate of speech therapy, grade
      failures, or needing Individualized Education Plans (IEPs). The objective of this
      study was to determine whether language skills and educational performance
      improved or worsened over time in a cohort of children with UHL. STUDY DESIGN:
      Prospective longitudinal cohort study. METHODS: Forty-six children with permanent
      UHL, ages 6 to 12 years, were studied using standardized cognitive, achievement,
      and language testing at yearly intervals for 3 years. Using standardized test
      scores allowed implicit comparison to norms established by national cross
      sectional samples. Secondary outcomes included behavioral issues, IEPs, receipt
      of speech therapy, or teacher report of problems at school. Analysis utilized
      repeated measures analysis of variance and multilevel random regression modeling.
      RESULTS: Several cognitive and language mean standardized scores increased over
      time. Possible predictors of increase with time included higher baseline
      cognitive levels and receipt of interventions through an IEP. However,
      standardized achievement scores and indicators of school performance did not show
      concomitant improvements. Rates of IEPs remained >50% throughout, and rates of
      speech therapy were consistently about 20%. CONCLUSIONS: Children with UHL
      demonstrated improvement in oral language and verbal intelligence quota scores
      over time, but not improvements in school performance. Parents and teachers
      reported persistent behavioral problems and academic weaknesses or areas of
      concern in about 25%. The provision of IEPs for children with UHL, and
      acknowledging UHL as a hearing disability, may be an effective intervention to
      improve language skills over time.

PMID- 22865631
TI  - Gallic acid downregulates matrix metalloproteinase-2 (MMP-2) and MMP-9 in human
      leukemia cells with expressed Bcr/Abl.
AB  - SCOPE: The aim of the present study was to explore the signaling pathways
      associated with gallic acid induced matrix metalloproteinase-2 (MMP-2)/MMP-9
      downregulation in human leukemia K562 cells. METHODS AND RESULTS: Unlike the
      insignificant effect on human Bcr/Abl-negative leukemia U937 cells, gallic acid
      attenuated invasion of human Bcr/Abl-positive leukemia K562 cells with
      characteristic of decreased protein expression and mRNA levels of MMP-2 and MMP
      9. Gallic acid induced beta-TrCP upregulation evoked Bcr/Abl degradation in K562
      cells, while overexpression of Bcr/Abl attenuated gallic acid induced MMP-2/MMP-9
      downregulation. Overexpression of Bcr/Abl restored the levels of phospho-ERK and
      phospho-Akt but not JNK phosphorylation in gallic acid treated K562 cells. Gallic
      acid treatment repressed Akt/ERK-mediated c-Fos phosphorylation and JNK1-mediated
      ATF-2 phosphorylation. c-Jun inactivation was mediated through gallic acid
      induced Akt/ERK and JNK inactivation. Knockdown of c-Fos, c-Jun, and ATF-2 by
      siRNA and luciferase promoter assay reflected that c-Jun/ATF-2 and c-Jun/c-Fos
      were, respectively, responsible for MMP-2 and MMP-9 expression in K562 cells.
      Chromatin immunoprecipitating assay showed that gallic acid reduced the binding
      of c-Jun/ATF-2 and c-Jun/c-Fos with promoter region of MMP-2 and MMP-9 genes,
      respectively. CONCLUSION: Our data indicate that MMP-2 and MMP-9 downregulation
      in gallic acid treated K562 cells are mediated through suppression of JNK1
      mediated c-Jun/ATF-2 and Akt/ERK-mediated c-Jun/c-Fos pathways, respectively.

PMID- 22865632
TI  - Epigenetic inactivation of endothelin-2 and endothelin-3 in colon cancer.
AB  - Endothelin-1 (ET-1) and its receptors are overexpressed in human cancers, but
      much less is known about the roles of ET-2 and ET-3 in cancer etiology. We sought
      to examine human and rat colon tumors for dysregulation of ET-2 and ET-3
      expression and determine the underlying mechanisms. Human primary colon cancers
      and carcinogen-induced rat colon tumors were subjected to real-time RT-PCR,
      immunoblotting and immunohistochemistry; EDN2 and EDN3 genes were examined by
      methylation-specific PCR, bisulfite sequencing and pyrosequencing; and forced
      expression of ET-2 and ET-3 was conducted in human colon cancer cells followed by
      real-time cell migration and invasion assays. Rat and human colon tumors had
      markedly reduced expression of ET-2 and ET-3 mRNA and protein compared with
      matched controls. Mechanistic studies revealed hypermethylation of EDN2 and EDN3
      genes in human primary colon cancers and in a panel of human colon cancer cell
      lines. Forced expression of ET-2 and ET-3 attenuated significantly the migration
      and invasion of human colon cancer cells. We conclude that epigenetic
      inactivation of ET-2 and ET-3 occurs frequently in both rat and human colon
      cancers. Current therapeutic strategies target overexpressed members of the ET
      axis via small molecule inhibitors and receptor antagonists, but this work
      supports a complementary approach based on the re-expression of ET-2 and ET-3 as
      natural antagonists of ET-1 in colon cancer.

PMID- 22865633
TI  - HPLC-ESI-MS/MS analysis and pharmacokinetics of luteoloside, a potential
      anticarcinogenic component isolated from Lonicera japonica, in beagle dogs.
AB  - Luteoloside is a potential anticarcinogenic component isolated from Lonicera
      japonica, a traditional Chinese medicine (TCM). This study details the
      development and validation of a sensitive and accurate HPLC-ESI-MS/MS method for
      the quantification of luteoloside in dog plasma. Sample pretreatment includes
      simple protein precipitation using methanol-acetonitrile (1:1, v/v). A Phenomenex
      Gemini C(18) column (2.0 * 50 mm, i.d., 3.5 um) was used to separate luteoloside
      and internal standard by gradient mode with mobile phase consisting of water
      containing 0.1% formic acid and methanol containing 0.1% formic acid at a flow
      rate of 0.40 mL/min with a column temperature of 25 degrees C. The detection was
      performed by positive ion electrospray ionization (ESI) in multiple reaction
      monitoring mode. The calibration curves were linear (R > 0.995) over the
      concentration range 1.0-2000 ng/mL and the lower limit of quantification was 1.0
      ng/mL. The intra-day and inter-day precisions (RSD) were all <15%, accuracies
      (RE) were within the range of +/-15%, and recoveries were between 85.0 and 115%.
      The validated HPLC-ESI-MS/MS method was successfully applied to determine plasma
      concentrations of luteoloside after intravenous administration of luteoloside at
      a dose level of 20 mg/kg.

PMID- 22865634
TI  - Hunsaker Mon-Jet tube ventilation: a 15-year experience.
AB  - OBJECTIVE/HYPOTHESIS: The Hunsaker Mon-Jet tube (HMJT) (Xomed, Jacksonville, FL)
      has been used effectively for subglottic ventilation. We previously reported a
      series of 552 patients over a 10-year period with no major complications. This is
      a continuation of that series with an additional 5 years of cases. STUDY DESIGN:
      Retrospective consecutive case series. METHODS: Patients who were ventilated with
      the HMJT for microlaryngeal surgery at the University of Washington Medical
      Center over a 15-year period (1995-2010) were identified from the Voice Disorders
      database. Charts were reviewed for demographic data, laryngeal diagnosis, and
      anesthetic parameters. Main outcome measure was the rate of complications.
      RESULTS: Fifty-seven complications occurred in 49 cases out of 839 cases (5.8%
      complication rate). In descending order, the complications were hypoxia (SpO(2)
      <90%, n = 30, 3.6%), hypercarbia (end tidal CO(2) of >60 mm Hg, n = 17, 2.0%),
      airway obstruction (n = 4, 0.5%), barotrauma (n = 2, 0.2%), seeding of blood into
      trachea (n = 2, 0.2%), submucosal injection of air (n = 1, 0.1%), and mucosal
      damage (n = 1, 0.1%). Factors associated with complications included high body
      mass index (P = .04), American Society of Anesthesiology class III or IV (P =
      .01), history of heart disease (P = .02), history of previous laryngeal surgery
      (P = .02), longer duration of case (P = .006), and laser use (P = .005).
      CONCLUSIONS: Although subglottic ventilation via an HMJT is a safe alternative to
      traditional endotracheal intubation in an appropriately selected population,
      practitioners should remain vigilant about the known complications.

PMID- 22865635
TI  - Aquatic toxicity of nanosilver colloids to different trophic organisms:
      contributions of particles and free silver ion.
AB  - The wide uses of nanosilver (nAg) have resulted in concerns regarding ecotoxicity
      to aquatic organisms. Some previous studies have found that the toxicity of nAg
      is due to the nanoparticles themselves, while others have found that ionic silver
      (Ag(+) ) released by nAg particles plays an important role. In the present study,
      the authors quantitatively evaluated the relative contribution of nAg particles
      and Ag(+) to the toxicity to three aquatic organisms of different trophic levels,
      including an algal species (Raphidocelis subcapitata), a cladoceran species
      (Chydorus sphaericus), and a freshwater fish larva (Danio rerio). A bare and a
      polyvinylpyrrolidone (PVP)-coated nAg as well as a monodispersed nAg with a
      dispersant (DIS-nAg) were examined. The toxicity of the nAg in the form of
      colloids decreased in the order DIS-nAg > PVP-nAg > Bare-nAg for all three
      trophic aquatic organisms (in terms of median effect concentration). The DIS-nAg
      had the highest and Bare-nAg the lowest concentration of free Ag(+) , implying
      that free Ag(+) cannot be neglected in explaining the toxicity of nAg colloids.
      Furthermore, the contribution of free Ag(+) to the toxicity of nAg colloids for
      R. subcapitata was the highest but for D. rerio the lowest, implying that the
      organisms tested have different accumulation abilities for Ag(+) or nAg
      particles.

PMID- 22865636
TI  - TBX3 promotes human embryonic stem cell proliferation and neuroepithelial
      differentiation in a differentiation stage-dependent manner.
AB  - T-box 3 (Tbx3) is a member of the T-box family of genes. Mutations that result in
      the haploinsufficiency of TBX3 cause ulnar mammary syndrome in humans
      characterized by mammary gland hypoplasia as well as other congenital defects. In
      mice, homozygous mutations are embryonic lethal, suggesting that Tbx3 is
      essential for embryo development. Studies in mice have shown that Tbx3 is
      essential in the maintenance of mouse embryonic stem cell (ESC) self-renewal and
      in their differentiation into extraembryonic endoderm (ExEn). The role TBX3 plays
      in regulating human ESCs (hESCs) has not been explored. Since mouse and hESCs are
      known to represent distinct pluripotent states, it is important to address the
      role of TBX3 in hESC self-renewal and differentiation. Using overexpression and
      knockdown strategies, we found that TBX3 overexpression promotes hESC
      proliferation possibly by repressing the expression of both NFkappaBIB and
      p14(ARF) , known cell cycle regulators. During differentiation, TBX3 knockdown
      resulted in decreased neural rosette formation and in decreased expression of
      neuroepithelial and neuroectoderm markers (PAX6, LHX2, FOXG1, and RAX). Taken
      together, our data suggest a role for TBX3 in hESC proliferation and reveal an
      unrecognized novel role of TBX3 in promoting neuroepithelial differentiation. Our
      results suggest that TBX3 plays distinct roles in regulating self-renewal and
      differentiation in both hESCs and mouse ESCs.

PMID- 22865637
TI  - Local coordination geometry and spin state in novel Fe(II) complexes with 2,6
      bis(pyrazol-3-yl)pyridine-type ligands as controlled by packing forces:
      structural correlations.
AB  - A substituted 2,6-bis(pyrazol-3-yl)pyridine (3-bpp) ligand, H(4)L, created to
      facilitate intermolecular interactions in the solid, has been used to obtain four
      novel Fe(II) complexes: [Fe(H(4)L)(2)](ClO(4))(2)?2 CH(3)NO(2)?2 H(2)O,
      [Fe(H(4)L)(H(2)LBF(2))](BF(4))?5 C(3)H(6)O (H(2)LBF(2) is an in situ modified
      version of H(4)L), [Fe(H(4)L)(2)](ClO(4))(2)?2 C(3)H(7)OH and
      [Fe(H(4)L)(2)](ClO(4))(2)?4 C(2)H(5)OH. Changing of spin-inactive components
      (solvents, anions or distant ligand substituents) causes differences to the
      coordination geometry of the metal that are key to the magnetic properties.
      Magnetic measurements show that, contrary to the previously published complex
      [Fe(H(4)L)(2)](ClO(4))(2)?H(2)O?2 CH(3)COCH(3), the newly synthesised compounds
      remain in the high-spin (HS) state at all temperatures (5-300 K). A member of the
      known family of Fe(II)/3-bpp complexes, [Fe(3-bpp)(2)](ClO(4))(2)?1.75
      CH(3)COCH(3)?1.5 Et(2)O, has also been prepared and characterised structurally.
      In the bulk, this compound exhibits a gradual and incomplete spin transition near
      205 K. The single-crystal structure is consistent with it being HS at 250 K and
      partially low spin at 90 K. Structural analysis of all these compounds reveals
      that the exact configuration of intermolecular interactions affects dramatically
      the local geometry at the metal, which ultimately has a strong influence on the
      magnetic properties. Along this line, the geometry of Fe(II) in all published 3
      bpp compounds of known structure has been examined, both by calculating various
      distortion indices (Sigma, Theta, theta and Phi) and by continuous shape measures
      (CShMs). The results reveal correlations between some of these parameters and
      indicate that the distortions from octahedral geometry observed on HS systems are
      mainly due to strains arising from intermolecular interactions. As previously
      suggested with other related compounds, we observe here that strongly HS
      distorted systems have a larger tendency to remain in that state.

PMID- 22865639
TI  - beta(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+) cell
      plasticity in vascular niches.
AB  - AIMS: The implication of circulating haematopoietic CD34(+) progenitors in the
      vasculature is unclear due to the lack of understanding of their characteristics
      and plasticity mediated by their cellular microenvironment. We investigated how
      vascular smooth muscle cells (SMCs) and their interactions with endothelial cells
      (ECs) affect the behaviour and plasticity of CD34(+)CD31(+) progenitors and the
      underlying mechanisms. METHODS AND RESULTS: Human peripheral blood-derived
      CD34(+)CD31(+) cells were directly transplanted into injured arteries in vivo and
      co-cultured with ECs and SMCs in vitro. CD34(+)CD31(+) progenitors injected into
      wire-injured mouse arteries differentiate into ECs and macrophages in the
      neoendothelial layer and neointima, respectively. SMC-co-culture increases
      CD34(+)CD31(+) cell mobility and adhesion to and transmigration across ECs.
      Sorted CD34(+)CD31(+) progenitors that adhered to ECs co-cultured with SMCs have
      the capacity to form capillary-like structures in Matrigel and chimeric blood
      vessels in vivo. Sorted transmigrated progenitors give rise to macrophages with
      increased pro-angiogenic activity. These differentiations of CD34(+)CD31(+)
      progenitors into ECs and macrophages are mediated by beta(2)-integrin and Notch
      1, respectively. beta(2)-Integrin and Notch-1 are activated by their
      counterligands, intercellular adhesion molecule-1 (ICAM-1) and jagged-1, which
      are highly expressed in the neoendothelium and neointima in injured arteries.
      Intra-arterial injection of beta(2)-integrin-activated CD34(+)CD31(+) progenitors
      into wire-injured mouse arteries inhibits neointima formation. CONCLUSION: Our
      findings indicate that the peripheral vascular niches composed of ECs and SMCs
      may predispose haematopoietic CD34(+)CD31(+) progenitors to differentiate into
      ECs and macrophages through the activations of the ICAM-1/beta(2)-integrin and
      jagged-1/Notch-1 cascades, respectively.

PMID- 22865641
TI  - Carbon-coated single-crystal LiMn2O4 nanoparticle clusters as cathode material
      for high-energy and high-power lithium-ion batteries.

PMID- 22865640
TI  - Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the
      heart.
AB  - AIMS: The ventricular wall of the heart is composed of trabeculated and compact
      layers, which are separated by yet unknown processes during embryonic
      development. Here, we wanted to explore the role of Notch2 and Numb/Numblike for
      myocardial trabeculation and compaction. METHODS AND RESULTS: We found that
      Notch2 activity is specifically down-regulated in the compact layer during
      cardiac development in the mouse. The biological role of Notch2 down-regulation
      was investigated by the expression of constitutively active Notch2 in the
      myocardium of transgenic mice, resulting in hypertrabeculation, reduced
      compaction, and ventricular septum defects. To disclose the mechanism that
      inhibited Notch2 activity during the formation of myocardial layers, we analysed
      potential suppressors of Notch signalling. We unveiled that concomitant but not
      separate ablation of Numb and Numblike in the developing heart leads to increased
      Notch2 activity along with hypertrabeculation, reduced compaction, and
      ventricular septum defects, phenocopying effects gained by overexpression of
      constitutively active Notch2. Expression profiling revealed a strong up
      regulation of Bmp10 in Numb/Numblike mutant hearts, which might also interfere
      with trabeculation and compaction. CONCLUSION: This study identified potential
      novel roles of Numb/Numblike in regulating trabeculation and compaction by
      inhibiting Notch2 and Bmp10 signalling.

PMID- 22865642
TI  - Regeneration of nucleus pulposus tissue in an ovine intervertebral disc
      degeneration model by cell-free resorbable polymer scaffolds.
AB  - Degeneration of intervertebral discs (IVDs) occurs frequently and is often
      associated with lower back pain. Recent treatment options are limited and treat
      the symptoms rather than regenerate the degenerated disc. Cell-free, freeze-dried
      resorbable polyglycolic acid (PGA)-hyaluronan implants were used in an ovine IVD
      degeneration model. The nucleus pulposus of the IVD was partially removed,
      endoscopically. PGA-hyaluronan implants were immersed in autologous sheep serum
      and implanted into the disc defect. Animals with nucleotomy only served as
      controls. The T2-weighted/fat suppression sequence signal intensity index of the
      operated discs, as assessed by magnetic resonance imaging (MRI), showed that
      implantation of the PGA-hyaluronan implant improved (p = 0.0066) the MRI signal
      compared to controls at 6 months after surgery. Histological analysis by
      haematoxylin and eosin and safranin O staining showed the ingrowth of cells with
      typical chondrocytic morphology, even cell distribution, and extracellular matrix
      rich in proteoglycan. Histomorphometric analyses confirmed that the implantation
      of the PGA-hyaluronan scaffolds improved (p = 0.027) the formation of regenerated
      tissue after nucleotomy. Disc heights remained stable in discs with nucleotomy
      only as well as after implantation of the implant. In conclusion, implantation of
      cell-free polymer-based implants after nucleotomy induces nucleus pulposus tissue
      regeneration and improves disc water content in the ovine model.

PMID- 22865643
TI  - A sample selection strategy for next-generation sequencing.
AB  - Next-generation sequencing technology provides us with vast amounts of sequence
      data. It is efficient and cheaper than previous sequencing technologies, but deep
      resequencing of entire samples is still expensive. Therefore, sensible strategies
      for choosing subsets of samples to sequence are required. Here we describe an
      algorithm for selection of a sub-sample of an existing sample if one has either
      of two possible goals in mind: maximizing the number of new polymorphic sites
      that are detected, or improving the efficiency with which the remaining
      unsequenced individuals can have their types imputed at newly discovered
      polymorphisms. We then describe a variation on our algorithm that is more focused
      on detecting rarer variants. We demonstrate the performance of our algorithm
      using simulated data and data from the 1000 Genomes Project.

PMID- 22865644
TI  - The effect of deep venous thrombosis on short-term outcomes and cost of care
      after head and neck cancer surgery.
AB  - OBJECTIVES/HYPOTHESIS: The Centers for Medicare and Medicaid Services has
      targeted deep venous thrombosis (DVT) and pulmonary embolus (PE) as preventable
      "never events" and has discontinued reimbursement for these conditions following
      selected orthopedic procedures. We sought to determine the relationship between
      DVT/PE and in-hospital mortality, postoperative complications, length of stay,
      and costs in head and neck cancer (HNCA) surgery. STUDY DESIGN: Retrospective
      cross-sectional study. METHODS: Discharge data from the Nationwide Inpatient
      Sample for 93,663 patients who underwent an ablative procedure for a malignant
      oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 2003 to 2008
      were analyzed using cross-tabulations and multivariate regression modeling.
      RESULTS: DVT/PE was diagnosed in 1,860 cases (2%) and was significantly
      associated with major surgical procedures (odds ratio [OR], 1.4; P = .048) and
      advanced comorbidity (OR, 1.7; P = .034). After controlling for all other
      variables, no association was found between a diagnosis of DVT/PE and obesity,
      weight loss, age, chronic cardiac disease, paralysis, and smoking in this HNCA
      surgical population. DVT/PE was associated with increased risk of in-hospital
      mortality (OR, 3.1; P = .001), postoperative surgical complications (OR, 2.1; P <
      .001), acute medical complications (OR, 1.9; P < .001), and was associated with
      significantly increased length of hospitalization and hospital-related costs.
      CONCLUSIONS: DVT/PE is uncommon in HNCA patients but is associated with increased
      mortality, postoperative complications, length of hospitalization, and hospital
      related costs. The lack of correlation with known modifiable variables suggests
      that despite advances in targeted prophylaxis, patients with advanced disease and
      comorbidity remain at increased risk. Caution must be used in the institution of
      reforms that threaten to inadequately reimburse the provision of care in
      vulnerable populations.

PMID- 22865645
TI  - Use of electron microscopy to classify canine perivascular wall tumors.
AB  - The histologic classification of canine perivascular wall tumors (PWTs) is
      controversial. Many PWTs are still classified as hemangiopericytomas (HEPs), and
      the distinction from peripheral nerve sheath tumors (PNSTs) is still under
      debate. A recent histologic classification of canine soft tissue sarcomas
      included most histologic types of PWT but omitted those that were termed
      undifferentiated. Twelve cases of undifferentiated canine PWTs were evaluated by
      transmission electron microscopy. The ultrastructural findings supported a
      perivascular wall origin for all cases with 4 categories of differentiation:
      myopericytic (n = 4), myofibroblastic (n = 1), fibroblastic (n = 2), and
      undifferentiated (n = 5). A PNST was considered unlikely in each case based on
      immunohistochemical expression of desmin and/or the lack of typical
      ultrastructural features, such as basal lamina. Electron microscopy was pivotal
      for the subclassification of canine PWTs, and the results support the hypothesis
      that canine PWTs represent a continuum paralleling the phenotypic plasticity of
      vascular mural cells. The hypothesis that a subgroup of PWTs could arise from a
      pluripotent mesenchymal perivascular wall cell was also considered and may
      explain the diverse differentiation of canine PWTs.

PMID- 22865646
TI  - Antihyperuricemic and nephroprotective effects of resveratrol and its analogues
      in hyperuricemic mice.
AB  - SCOPE: Stilbenes, of which, resveratrol is a representative compound in foods and
      plants, possess a variety of bioactivities including antioxidation, anti
      inflammation, chemoprevention, and cardioprotection. This study was conducted to
      evaluate the antihyperuricemic and nephroprotective effects of resveratrol and
      its analogues and explore the possible mechanisms. The structure-activity
      relationships were analyzed. METHODS AND RESULTS: Potassium oxonate-induced
      hyperuricemic mice were dosed by gavage with eight stilbenes. Uric acid,
      creatinine, and blood urea nitrogen (BUN) levels in serum and urine, clearance
      rate of creatinine and BUN, 24-h urate excretion, and fractional excretion of
      uric acid, uromodulin levels in urine and kidney were determined to evaluate
      renal urate handling and function. Renal protein levels of organic ion
      transporters were detected to elucidate the possible mechanisms. Resveratrol,
      trans-4-hydroxystilbene, pterostilbene, polydatin, and mulberroside A were found
      to have antihyperuricemic activities. These compounds together with trans-2
      hydroxystilbene provided nephroprotection. Trans-3,4',5-trimethoxystilbene and
      cis-combretastatin A-4 had no effects. CONCLUSION: The uricosuric and
      nephroprotective actions of resveratrol and its analogues were mediated by
      regulating renal organic ion transporters in hyperuricemic mice, supporting their
      beneficial effects for the prevention of hyperuricemia. The number and position,
      methoxylation and glycosylation of hydroxyl groups in these trans-stilbenes were
      required for their effects.

PMID- 22865648
TI  - LC-MS/MS-ESI method for simultaneous quantitation of metformin and repaglinidie
      in rat plasma and its application to pharmacokinetic study in rats.
AB  - A highly sensitive and specific LC-MS/MS-ESI method has been developed for
      simultaneous quantification of metformin (MFN) and repaglinide (RGN) in rat
      plasma (50 MUL) using phenacetin as an internal standard (IS). Simple protein
      precipitation was used to extract MFN and RGN from rat plasma. The
      chromatographic resolution of MFN, RGN and IS was achieved with a mobile phase
      consisting of 0.2% formic acid in water-acetonitrile (1:1, v/v) with a time
      program flow gradient on a Chromolith RP-18e column. The total chromatographic
      run time was 3.5 min and the elution of MFN, RGN and IS occurred at 1.64, 2.21
      and 2.15 min, respectively. A linear response function was established for the
      range of concentrations 0.855-394 and 0.021-21.7 ng/mL for MFN and RGN,
      respectively. The intra- and inter-day precision values for MFN and RGN met the
      acceptance as per FDA guidelines. MFN and RGN were stable in battery of stability
      studies viz., bench-top, auto-sampler and freeze-thaw cycles. The developed assay
      was applied to a pharmacokinetic study in rats.

PMID- 22865647
TI  - Breastmilk is a novel source of stem cells with multilineage differentiation
      potential.
AB  - The mammary gland undergoes significant remodeling during pregnancy and
      lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation.
      The scarcity of human lactating breast tissue specimens and the low numbers and
      quiescent state of MaSCs in the resting breast have hindered understanding of
      both normal MaSC dynamics and the molecular determinants that drive their
      aberrant self-renewal in breast cancer. Here, we demonstrate that human
      breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk
      cells from different donors displayed variable expression of pluripotency genes
      normally found in human embryonic stem cells (hESCs). These genes included the
      transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self
      renewal circuitry of hESCs. When cultured in the presence of mouse embryonic
      feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like
      colony morphology and phenotype and could be passaged in secondary and tertiary
      clonogenic cultures. While self-renewal TFs were found silenced in the normal
      resting epithelium, they were dramatically upregulated in breastmilk cells
      cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro
      into cell lineages from all three germ layers. These findings provide evidence
      that breastmilk represents a novel and noninvasive source of patient-specific
      stem cells with multilineage potential and establish a method for expansion of
      these cells in culture. They also highlight the potential of these cells to be
      used as novel models to understand adult stem cell plasticity and breast cancer,
      with potential use in bioengineering and tissue regeneration.

PMID- 22865649
TI  - The expanding frontier of hematopoietic cell transplantation.
AB  - Over the past several decades there has been a tremendous expansion of the
      indications for hematopoietic cell transplantation. This growth has been possible
      because of advances in supportive care, more effective graft versus host disease
      prophylaxis and the advent of reduced intensity conditioning regimens which have
      greatly reduced transplant related morbidity and allowed for the transplantation
      of older patients and patients with significant co-morbid disease. The role of
      flow cytometry in transplantation is crucial to both clinical care, for accuracy
      of diagnosis and monitoring of disease, and research. In this review, we
      highlight some of the important advances that have been made in the field,
      including the use of alternative donors for transplantation, novel therapies for
      the myeloid malignancies, which remain the prototype diseases for
      transplantation, and advances in diagnosis and treatment of graft versus host
      disease, which is the principal complication of allogeneic hematopoietic cell
      transplantation. Future directions in hematopoietic cell transplantation,
      particularly those that attempt to modulate the post-transplant cellular
      environment to favor separation of graft versus host disease from the graft
      versus tumor effects of the transplant are discussed.

PMID- 22865651
TI  - Ossicular fusion and cholesteatoma in auriculo-condylar syndrome: in vivo
      evidence of arrest of embryogenesis.
AB  - Auriculo-condylar syndrome (ACS) is a rare condition affecting first branchial
      arch structures. The types of hearing loss and temporal bone findings in ACS have
      not been reported. We describe a 14-year-old male with constricted pinnae,
      mandibular dysostosis, glossoptosis, a high-arched palate, hearing loss, and
      cholesteatoma. Computed tomography imaging demonstrated malleoincudal joint
      ankylosis. The fused malleoincudal complex was removed during mastoidectomy for
      cholesteatoma. Electron microscopy and histopathology of the joint suggested the
      fusion was congenital. This is the first report of ossicular fusion and
      cholesteatoma in ACS and the most detailed in vivo evidence of disruption of
      embryogenesis during malleoincudal joint formation.

PMID- 22865650
TI  - Overexpression of ZAC impairs glucose-stimulated insulin translation and
      secretion in clonal pancreatic beta-cells.
AB  - BACKGROUND: ZAC (Zinc finger protein that regulates apoptosis and cell-cycle
      arrest) is a candidate gene for transient neonatal diabetes mellitus (TNDM). This
      condition involves severe insulin deficiency at birth that reverses over weeks or
      months but may relapse with diabetes recurring in later life. ZAC overexpression
      in transgenic mice has previously been shown to result in complex changes in both
      beta-cell mass and possibly function. The present study therefore aimed to
      examine the role of ZAC in beta-cell function in vitro, independent of the
      confounder of a reduced beta-cell mass at birth. METHODS: Overexpression of ZAC
      was achieved through the tetracycline-regulatable system in the beta-cell line,
      INS-1. RESULTS: We found that ZAC overexpression exerted no significant effect on
      proliferation in this transformed cell line at any of the glucose concentrations
      examined. By contrast, glucose-stimulated insulin secretion was impaired through
      a mechanism downstream of cytosolic Ca(2+) increases. Furthermore, glucose
      stimulated proinsulin biosynthesis was inhibited despite an increase in insulin
      transcript level. Finally, we found that glucose downregulated ZAC expression in
      both INS-1 cells and primary mouse islets. CONCLUSIONS: These results indicate
      that ZAC is a negative regulator of the acute stimulatory effects of glucose on
      beta-cells, and provide a possible explanation for both insulin deficiency in the
      neonate and the later relapse of diabetes in patients with transient neonatal
      diabetes mellitus cases.

PMID- 22865652
TI  - In silico structure-function analysis of E. cloacae nitroreductase.
AB  - Reduction, catalyzed by the bacterial nitroreductases, is the quintessential
      first step in the biodegradation of a variety of nitroaromatic compounds from
      contaminated waters and soil. The Enterobacter cloacae nitroreductase (EcNR)
      enzyme is considered as a prospective biotechnological tool for bioremediation of
      hazardous nitroaromatic compounds. Using diverse computational methods, we obtain
      insights into the structural basis of activity and mechanism of its function. We
      have performed molecular dynamics simulation of EcNR in three different states
      (free EcNR in oxidized form, fully reduced EcNR with benzoate inhibitor and fully
      reduced EcNR with nitrobenzene) in explicit solvent and with full electrostatics.
      Principal Component Analysis (PCA) of the variance-covariance matrix showed that
      the complexed nitroreductase becomes more flexible overall upon complexation,
      particularly helix H6, in the vicinity of the binding site. A multiple sequence
      alignment was also constructed in order to examine positional constraints on
      substitution in EcNR. Five regions which are highly conserved within the flavin
      mononucleotide (FMN) binding site were identified. Obtained results and their
      implications for EcNR functioning are discussed, and new plausible mechanism has
      been proposed.

PMID- 22865654
TI  - Chlorophacinone residues in mammalian prey at a black-tailed prairie dog colony.
AB  - Black-tailed prairie dogs (BTPDs), Cynomys ludovicianus, are an important prey
      for raptors; therefore, the use of the rodenticide Rozol (0.005% chlorophacinone
      active ingredient) to control BTPDs raises concern for secondary poisonings
      resulting from the consumption of contaminated prey by raptors. In the present
      study, the authors observed Rozol exposure and adverse effects to mammalian prey
      on 11 of 12 search days of the study. Mammalian hepatic chlorophacinone residues
      ranged from 0.44 to 7.56 ug/g. Poisoned prey availability was greater than
      previously reported.

PMID- 22865655
TI  - Hydrogen bonding directed supramolecular polymerisation of oligo(phenylene
      ethynylene)s: cooperative mechanism, core symmetry effect and chiral
      amplification.
AB  - The design of supramolecular motifs with tuneable stability and adjustable
      supramolecular polymerisation mechanisms is of crucial importance to precisely
      control the properties of supramolecular assemblies. This report focuses on
      constructing pi-conjugated oligo(phenylene ethynylene) (OPE)-based one
      dimensional helical supramolecular polymers that show a cooperative growth
      mechanism. Thus, a novel set of discotic molecules comprising a rigid OPE core,
      three amide groups, and peripheral solubilising wedge groups featuring C(3) and
      C(2) core symmetry was designed and synthesised. All of the discotic molecules
      are crystalline compounds and lack a columnar mesophase in the solid state. In
      dilute methylcyclohexane solution, one-dimensional supramolecular polymers are
      formed stabilised by threefold intermolecular hydrogen bonding and pi-pi
      interactions, as evidenced by (1)H NMR measurements. Small-angle X-ray and light
      scattering measurements reveal significant size differences between the columnar
      aggregates of C(3)- and C(2)-symmetrical discotics, that is, the core symmetry
      strongly influences the nature of the supramolecular polymerisation process.
      Temperature-dependent CD measurements show a highly cooperative polymerisation
      process for the C(3)-symmetrical discotics. In contrast, the self-assembly of
      C(2)-symmetrical discotics shows a smaller enthalpy release upon aggregation and
      decreased cooperativity. In all cases, the peripheral stereogenic centres induce
      a preferred handedness in the columnar helical aggregates. Moreover, one
      stereogenic centre suffices to fully bias the helicity in the C(2)-symmetrical
      discotics. Finally, chiral amplification studies with the C(3)-symmetrical
      discotics were performed by mixing chiral and achiral discotics (sergeants-and
      soldiers experiment) and discotics of opposite chirality (majority-rules
      experiment). The results demonstrate a very strong sergeants-and-soldiers effect
      and a rather weak majority-rules effect.

PMID- 22865653
TI  - Role of GRB2-associated binder 1 in epidermal growth factor receptor-induced
      signaling in head and neck squamous cell carcinoma.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in the
      pathogenesis of head and neck squamous cell carcinoma (HNSCC). Despite the high
      expression of EGFR in HNSCC, EGFR inhibitors have only limited success as
      monotherapy. The Grb2-associated binder (GAB) family of adaptor proteins acts as
      docking/scaffolding molecules downstream of tyrosine kinase receptors. We
      hypothesized that GAB1 may amplify EGFR-induced signaling in HNSCCs and therefore
      could play a role in the reduced sensitivity of HNSCC to EGFR inhibitors. We used
      representative human HNSCC cell lines overexpressing wild type EGFR, and
      expressing GAB1 but not GAB2. We demonstrated that baseline Akt and MAPK
      signaling were reduced in HNSCC cells in which GAB1 expression was reduced.
      Furthermore, the maximal EGF-induced activation of the Akt and MAPK pathway was
      reduced and delayed, and the duration of the EGF-induced activation of these
      pathways was reduced in cells with GAB1 knock-down. In agreement with this, HNSCC
      cells in which GAB1 levels were reduced showed an increased sensitivity to the
      EGFR inhibitor gefitinib. Our work demonstrates that GAB1 plays an important role
      as part of the mechanism of by which EGFR induces induced activation of the MAPK
      and AKT pathway. Our results identify GAB1 as an amplifier of the EGFR-initiated
      signaling, which may also interfere with EGFR degradation. These findings support
      the emerging notion that reducing GAB1 function may sensitize HNSCC to EGFR
      inhibitors, hence representing a new therapeutic target HNSCC treatment in
      combination with EGFR targeting agents.

PMID- 22865656
TI  - FM19G11 favors spinal cord injury regeneration and stem cell self-renewal by
      mitochondrial uncoupling and glucose metabolism induction.
AB  - Spinal cord injury is a major cause of paralysis with no currently effective
      therapies. Induction of self-renewal and proliferation of endogenous regenerative
      machinery with noninvasive and nontoxic therapies could constitute a real hope
      and an alternative to cell transplantation for spinal cord injury patients. We
      previously showed that FM19G11 promotes differentiation of adult spinal cord
      derived ependymal stem cells under hypoxia. Interestingly, FM19G11 induces self
      renewal of these ependymal stem cells grown under normoxia. The analysis of the
      mechanism of action revealed an early increment of mitochondrial uncoupling
      protein 1 and 2 with an early drop of ATP, followed by a subsequent compensatory
      recovery with activated mitochondrial metabolism and the induction of glucose
      uptake by upregulation of the glucose transporter GLUT-4. Here we show that
      phosphorylation of AKT and AMP-activated kinase (AMPK) is involved in FM19G11
      dependent activation of GLUT-4, glucose influx, and consequently in stem cell
      self-renewal. Small interfering RNA of uncoupling protein 1/2, GLUT-4 and
      pharmacological inhibitors of AKT, mTOR and AMPK signaling blocked the FM19G11
      dependent induction of the self-renewal-related markers Sox2, Oct4, and Notch1.
      Importantly, FM19G11-treated animals showed accelerated locomotor recovery. In
      vivo intrathecal sustained administration of FM19G11 in rats after spinal cord
      injury showed more neurofilament TUJ1-positive fibers crossing the injured area
      surrounded by an increase of neural precursor Vimentin-positive cells. Overall,
      FM19G11 exerts an important influence on the self-renewal of ependymal stem
      progenitor cells with a plausible neuroprotective role, providing functional
      benefits for spinal cord injury treatment.

PMID- 22865657
TI  - Discovery of the DNA "genetic code" for abiological gold nanoparticle
      morphologies.
AB  - DNA is in control: Different combinations of DNA nucleotides can control the
      shape and surface roughness of gold nanoparticles during their synthesis. These
      nanoparticles were synthesized in the presence of either homogenous
      oligonucleotides or mixed-base oligonucleotides using gold nanoprisms as seeds.
      The effect of the individual DNA bases and their combinations on shape control
      are shown in the figure.

PMID- 22865658
TI  - Subject-specific models of susceptibility-induced B0 field variations in breast
      MRI.
AB  - PURPOSE: To rapidly calculate and validate subject-specific field maps based on
      the three-dimensional shape of the bilateral breast volume. MATERIALS AND
      METHODS: Ten healthy female volunteers were scanned at 3 Tesla using a multi-echo
      sequence that provides water, fat, in-phase, out-of-phase, and field map images.
      A shape-specific binary mask was automatically generated to calculate a computed
      field map using a dipole field model. The measured and computed field maps were
      compared by visualizing the spatial distribution of the difference field map, the
      mean absolute error, and the 80% distribution widths of frequency histograms.
      RESULTS: The 10 computed field maps had a mean absolute error of 38 Hz (0.29 ppm)
      compared with the measured field maps. The average 80% distribution widths for
      the histograms of all of the computed, measured, and difference field maps are
      205 Hz, 233 Hz, and 120 Hz, respectively. CONCLUSION: The computed field maps had
      substantial overall agreement with the measured field maps, indicating that
      breast MRI field maps can be computed based on the air-tissue interfaces. These
      estimates may provide a predictive model for field variations and thus have the
      potential to improve applications in breast MRI.

PMID- 22865659
TI  - An isoreticular family of microporous metal-organic frameworks based on zinc and
      2-substituted imidazolate-4-amide-5-imidate: syntheses, structures and
      properties.
AB  - We report on a new series of isoreticular frameworks based on zinc and 2
      substituted imidazolate-4-amide-5-imidate (IFP-1-4, IFP = imidazolate framework
      Potsdam) that form one-dimensional, microporous hexagonal channels. Varying R in
      the 2-substitued linker (R = Me (IFP-1), Cl (IFP-2), Br (IFP-3), Et (IFP-4))
      allowed the channel diameter (4.0-1.7 A), the polarisability and functionality of
      the channel walls to be tuned. Frameworks IFP-2, IFP-3 and IFP-4 are
      isostructural to previously reported IFP-1. The structures of IFP-2 and IFP-3
      were solved by X-ray crystallographic analyses. The structure of IFP-4 was
      determined by a combination of PXRD and structure modelling and was confirmed by
      IR spectroscopy and (1)H MAS and (13)C CP-MAS NMR spectroscopy. All IFPs showed
      high thermal stability (345-400  degrees C); IFP-1 and IFP-4 were stable in
      boiling water for 7 d. A detailed porosity analysis was performed on the basis of
      adsorption measurements by using various gases. The potential of the materials to
      undergo specific interactions with CO(2) was investigated by measuring the
      isosteric heats of adsorption. The capacity to adsorb CH(4) (at 298 K), CO(2) (at
      298 K) and H(2) (at 77 K) at high pressure were also investigated. In situ IR
      spectroscopy showed that CO(2) is physisorbed on IFP-1-4 under dry conditions and
      that both CO(2) and H(2)O are physisorbed on IFP-1 under moist conditions.

PMID- 22865661
TI  - Surgery for obstructive sleep apnea: sleep endoscopy determinants of outcome.
AB  - OBJECTIVES/HYPOTHESIS: Although drug-induced sleep endoscopy is often employed to
      determine the site of obstruction in patients with obstructive sleep apnea (OSA)
      who will undergo upper airway surgery, it remains unknown whether its findings
      are associated with surgical outcome. This study tested the hypothesis that drug
      induced sleep endoscopy variables can predict the outcome of upper airway surgery
      in OSA patients. STUDY DESIGN: Case series retrospective analysis. METHODS: Forty
      nine OSA patients (41 male; mean apnea-hypopnea index [AHI] 30.9 +/- 18.5
      events/hour) underwent propofol-induced sleep endoscopy followed by upper airway
      surgery (palatal surgery, and/or radiofrequency ablation of the tongue base,
      and/or hyoid suspension) and subsequently a follow-up polysomnography to assess
      surgical outcome. RESULTS: Twenty-three patients (47%) were responders, and
      twenty-nine were nonresponders (53%). Nonresponders had a higher occurrence of
      complete or partial circumferential collapse at velum and complete antero
      posterior collapse at tongue base or epiglottis in comparison with responders.
      Multivariate logistic regression analysis revealed that among baseline clinical
      and polysomnographic characteristics (e.g., AHI, body mass index) and sleep
      endoscopy findings, the presence of complete circumferential collapse at velum,
      and of complete antero-posterior collapse at tongue base were the only
      independent predictors of upper airway surgery failure. CONCLUSIONS: Drug-induced
      sleep endoscopy can be used to predict higher likelihood of response to upper
      airway surgery in OSA.

PMID- 22865660
TI  - New transgenic reporters identify somatosensory neuron subtypes in larval
      zebrafish.
AB  - To analyze somatosensory neuron diversity in larval zebrafish, we identified
      several enhancers from the zebrafish and pufferfish genomes and used them to
      create five new reporter transgenes. Sequential deletions of three of these
      enhancers identified small sequence elements sufficient to drive expression in
      zebrafish trigeminal and Rohon-Beard (RB) neurons. One of these reporters, using
      the Fru.p2x3-2 enhancer, highlighted a somatosensory neuron subtype that
      expressed both the p2rx3a and pkcalpha genes. Comparison with a previously
      described trpA1b reporter revealed that it highlighted the same neurons as the
      Fru.p2x3-2 reporter. To determine whether neurons of this subtype possess
      characteristic peripheral branching morphologies or central axon projection
      patterns, we analyzed the morphology of single neurons. Surprisingly, although
      these analyses revealed diversity in peripheral axon branching and central axon
      projection, PKCalpha/p2rx3a/trpA1b-expressing RB cells did not possess obvious
      characteristic morphological features, suggesting that even within this
      molecularly defined subtype, individual neurons may possess distinct properties.
      The new transgenes created in this study will be powerful tools for further
      characterizing the molecular, morphological, and developmental diversity of
      larval somatosensory neurons.

PMID- 22865662
TI  - Identifying plausible genetic models based on association and linkage results:
      application to type 2 diabetes.
AB  - When planning resequencing studies for complex diseases, previous association and
      linkage studies can constrain the range of plausible genetic models for a given
      locus. Here, we explore the combinations of causal risk allele frequency (RAFC )
      and genotype relative risk (GRRC ) consistent with no or limited evidence for
      affected sibling pair (ASP) linkage and strong evidence for case-control
      association. We find that significant evidence for case-control association
      combined with no or moderate evidence for ASP linkage can define a lower bound
      for the plausible RAFC . Using data from large type 2 diabetes (T2D) linkage and
      genome-wide association study meta-analyses, we find that under reasonable model
      assumptions, 23 of 36 autosomal T2D risk loci are unlikely to be due to causal
      variants with combined RAFC < 0.005, and four of the 23 are unlikely to be due to
      causal variants with combined RAFC < 0.05. 

PMID- 22865663
TI  - A three-level mixed-effects location scale model with an application to
      ecological momentary assessment data.
AB  - In studies using ecological momentary assessment (EMA), or other intensive
      longitudinal data collection methods, interest frequently centers on changes in
      the variances, both within-subjects and between-subjects. For this, Hedeker et
      al. (Biometrics 2008; 64: 627-634) developed an extended two-level mixed-effects
      model that treats observations as being nested within subjects and allows
      covariates to influence both the within-subjects and between-subjects variance,
      beyond their influence on means. However, in EMA studies, subjects often provide
      many responses within and across days. To account for the possible systematic day
      to-day variation, we developed a more flexible three-level mixed-effects location
      scale model that treats observations within days within subjects, and allows
      covariates to influence the variance at the subject, day, and observation level
      (over and above their usual effects on means) using a log-linear representation
      throughout. We provide details of a maximum likelihood solution and demonstrate
      how SAS PROC NLMIXED can be used to achieve maximum likelihood estimates in an
      alternative parameterization of our proposed three-level model. The accuracy of
      this approach using NLMIXED was verified by a series of simulation studies. Data
      from an adolescent mood study using EMA were analyzed to demonstrate this
      approach. The analyses clearly show the benefit of the proposed three-level model
      over the existing two-level approach. The proposed model has useful applications
      in many studies with three-level structures where interest centers on the joint
      modeling of the mean and variance structure.

PMID- 22865664
TI  - Lubricin in human breast tissue expander capsules.
AB  - Capsular contraction is the most common complication of breast reconstruction
      surgery. While presence of the contractile protein alpha smooth muscle actin
      (alpha-SMA) is considered among the causes of capsular contraction, the exact
      etiology and pathophysiology is not fully understood. The objective of this study
      was to investigate the possible role of lubricin in capsular formation and
      contraction by determining the presence and distribution of the lubricating
      protein lubricin in human breast tissue expander capsules. Related aims were to
      evaluate select histopathologic features of the capsules, and the percentage of
      cells expressing alpha-SMA, which reflects the myofibroblast phenotype. Capsules
      from tissue expanders were obtained from eight patients. Lubricin, at the tissue
      implant interface, in the extracellular matrix, and in cells, and alpha-SMA
      containing cells were evaluated immunohistochemically. The notable finding was
      that lubricin was identified in all tissue expander capsules: as a discrete layer
      at the tissue-implant interface, extracellular, and intracellular. There was a
      greater amount of lubricin in the extracellular matrix in the intimal-subintimal
      zone when compared with the tissue away from the implant. Varying degrees of
      synovial metaplasia were seen at the tissue-implant interface. alpha-SMA
      containing cells were also seen in all but one patient. The findings might help
      us better understand factors involved in capsule formation.

PMID- 22865665
TI  - The timely completion of objective assessment tools for evaluation of technical
      skills.
AB  - OBJECTIVES/HYPOTHESIS: To this date the effect of the time taken to complete an
      evaluation on the psychometric properties of the instrument has not been
      reported. The goal of our study was to assess the effect of time taken to
      complete an evaluation on its validity. STUDY DESIGN: Cross-sectional validation
      study. METHODS: The global and checklist parts of tonsillectomy, mastoidectomy,
      rigid bronchoscopy, and endoscopic sinus surgery were used in the operating room
      by the otolaryngology faculty to evaluate the surgical skills of the residents.
      We categorized evaluations into two groups depending on the time taken to
      complete an evaluation (group A <= 6 days, group B >6 days). Construct validity
      was calculated for both groups by comparing the mean global and checklist scores
      of the residents across advancing postgraduate year levels. RESULTS: A total of
      468 evaluations, consisting of global and checklist parts, were completed for 29
      residents by 32 evaluators. Mean number of days taken to complete an evaluation
      was 7.7 days. For all the evaluations completed within a 6-day time period, the
      construct validity was significant for both global and checklist parts of the
      four instruments. In cases of the evaluations completed after 6 days, the
      construct validity was significant for the tonsillectomy instrument only.
      CONCLUSIONS: Our results indicate that the time taken to complete an evaluation
      has a significant effect on the construct validity of the objective instrument.
      In the future, efforts should be focused on faculty development to ensure timely
      completion of the evaluation for a more valid assessment process.

PMID- 22865666
TI  - Anisotropic Janus catalysts for spatially controlled chemical reactions.

PMID- 22865667
TI  - Human serine protease HTRA1 positively regulates osteogenesis of human bone
      marrow-derived mesenchymal stem cells and mineralization of differentiating bone
      forming cells through the modulation of extracellular matrix protein.
AB  - Mammalian high-temperature requirement serine protease A1 (HTRA1) is a secreted
      member of the trypsin family of serine proteases which can degrade a variety of
      bone matrix proteins and as such has been implicated in musculoskeletal
      development. In this study, we have investigated the role of HTRA1 in mesenchymal
      stem cell (MSC) osteogenesis and suggest a potential mechanism through which it
      controls matrix mineralization by differentiating bone-forming cells. Osteogenic
      induction resulted in a significant elevation in the expression and secretion of
      HTRA1 in MSCs isolated from human bone marrow-derived MSCs (hBMSCs), mouse
      adipose-derived stromal cells (mASCs), and mouse embryonic stem cells.
      Recombinant HTRA1 enhanced the osteogenesis of hBMSCs as evidenced by significant
      changes in several osteogenic markers including integrin-binding sialoprotein
      (IBSP), bone morphogenetic protein 5 (BMP5), and sclerostin, and promoted matrix
      mineralization in differentiating bone-forming osteoblasts. These stimulatory
      effects were not observed with proteolytically inactive HTRA1 and were abolished
      by small interfering RNA against HTRA1. Moreover, loss of HTRA1 function resulted
      in enhanced adipogenesis of hBMSCs. HTRA1 Immunofluorescence studies showed
      colocalization of HTRA1 with IBSP protein in osteogenic mASC spheroid cultures
      and was confirmed as being a newly identified HTRA1 substrate in cell cultures
      and in proteolytic enzyme assays. A role for HTRA1 in bone regeneration in vivo
      was also alluded to in bone fracture repair studies where HTRA1 was found
      localized predominantly to areas of new bone formation in association with IBSP.
      These data therefore implicate HTRA1 as having a central role in osteogenesis
      through modification of proteins within the extracellular matrix.

PMID- 22865668
TI  - (1) H NMR analysis of O-methyl-inositol isomers: a joint experimental and
      theoretical study.
AB  - Density functional theory (DFT) calculations of (1) H NMR chemical shifts for l
      quebrachitol isomers were performed using the B3LYP functional employing the 6
      31G(d,p) and 6-311 + G(2d,p) basis sets. The effect of the solvent on the B3LYP
      calculated NMR spectrum was accounted for using the polarizable continuum model.
      Comparison is made with experimental (1) H NMR spectroscopic data, which shed
      light on the average uncertainty present in DFT calculations of chemical shifts
      and showed that the best match between experimental and theoretical B3LYP (1) H
      NMR profiles is a good strategy to assign the molecular structure present in the
      sample handled in the experimental measurements. Among four plausible O-methyl
      inositol isomers, the l-quebrachitol 2a structure was unambiguously assigned
      based only on the comparative analysis of experimental and theoretical (1) H NMR
      chemical shift data. The B3LYP infrared (IR) spectrum was also calculated for the
      four isomers and compared with the experimental data, with analysis of the
      theoretical IR profiles corroborating assignment of the 2a structure. Therefore,
      it is confirmed in this study that a combined experimental/DFT spectroscopic
      investigation is a powerful tool in structural/conformational analysis studies.

PMID- 22865669
TI  - Aluminum induces oxidative burst, cell wall NADH peroxidase activity, and DNA
      damage in root cells of Allium cepa L.
AB  - Plants under stress incur an oxidative burst that involves a rapid and transient
      overproduction of reactive oxygen species (ROS: O(2) (*-) , H(2) O(2) , (*) OH).
      We hypothesized that aluminum (Al), an established soil pollutant that causes
      plant stress, would induce an oxidative burst through the activation of cell wall
      NADH peroxidase (NADH-PX) and/or plasma membrane-associated NADPH oxidase (NADPH
      OX), leading to DNA damage in the root cells of Allium cepa L. Growing roots of
      A. cepa were treated with Al(3+) (800 MUM of AlCl(3) ) for 3 or 6 hr without or
      with the pretreatment of inhibitors specific to NADH-PX and NADPH-OX for 2 hr. At
      the end of the treatment, the extent of ROS generation, cell death, and DNA
      damage were determined. The cell wall-bound protein (CWP) fractions extracted
      from the untreated control and the Al-treated roots under the aforementioned
      experimental conditions were also subjected to in vitro studies, which measured
      the extent of activation of peroxidase/oxidase, generation of (*) OH, and DNA
      damage. Overall, the present study demonstrates that the cell wall-bound NADH-PX
      contributes to the Al-induced oxidative burst through the generation of ROS that
      lead to cell death and DNA damage in the root cells of A. cepa. Furthermore, the
      in vitro studies revealed that the CWP fraction by itself caused DNA damage in
      the presence of NADH, supporting a role for NADH-PX in the stress response.
      Altogether, this study underscores the crucial function of the cell wall-bound
      NADH-PX in the oxidative burst-mediated cell death and DNA damage in plants under
      Al stress.

PMID- 22865670
TI  - Combined effects of temperature and pyriproxyfen stress in a full life-cycle test
      with Chironomus riparius (Insecta).
AB  - Traditional risk assessment guidelines employ acute or chronic toxicity tests for
      a maximum of one generation of organisms. These tests are usually performed in
      the laboratory at a constant standard temperature, although in the field
      organisms may experience different temperatures, which may be a source of
      additional stress. Climate change-related temperature shifts may have serious
      impacts on ectotherm populations that are key components of the aquatic food
      chains, particularly in combination with the exposure of pollutants affecting
      their development. Here, a chronic full life-cycle test with Chironomus riparius
      from the first-instar larvae in the parental (P) generation until emergence in
      the subsequent F1 generation was conducted at different temperatures (16 and 24
      degrees C), testing the effect of the insect growth regulator pyriproxyfen at 1,
      3, 10, 30, and 100 ug/L. The emergence ratios were significantly affected by the
      interaction of temperature, chemical treatment, and generation, showing that, at
      lower temperatures, the negative effects of pyriproxyfen exposure were
      significantly greater in the F1 generation than in the P generation. The
      development rate showed that the effects of the interactions were significant in
      the F1 generation, underscoring the importance of extended exposure as a useful
      amendment to the risk assessment of those agrochemicals potentially influencing
      developmental and reproductive parameters in intact organisms. Moreover, results
      demonstrated that any difference from the standard temperature of 20 degrees C
      might result in additional stress, leading to disruption of biological functions
      in C. riparius, highlighting the interaction among different global climate
      change-related variables.

PMID- 22865671
TI  - Key principles for a national clinical decision support knowledge sharing
      framework: synthesis of insights from leading subject matter experts.
AB  - OBJECTIVE: To identify key principles for establishing a national clinical
      decision support (CDS) knowledge sharing framework. MATERIALS AND METHODS: As
      part of an initiative by the US Office of the National Coordinator for Health IT
      (ONC) to establish a framework for national CDS knowledge sharing, key
      stakeholders were identified. Stakeholders' viewpoints were obtained through
      surveys and in-depth interviews, and findings and relevant insights were
      summarized. Based on these insights, key principles were formulated for
      establishing a national CDS knowledge sharing framework. RESULTS: Nineteen key
      stakeholders were recruited, including six executives from electronic health
      record system vendors, seven executives from knowledge content producers, three
      executives from healthcare provider organizations, and three additional experts
      in clinical informatics. Based on these stakeholders' insights, five key
      principles were identified for effectively sharing CDS knowledge nationally.
      These principles are (1) prioritize and support the creation and maintenance of a
      national CDS knowledge sharing framework; (2) facilitate the development of high
      value content and tooling, preferably in an open-source manner; (3) accelerate
      the development or licensing of required, pragmatic standards; (4) acknowledge
      and address medicolegal liability concerns; and (5) establish a self-sustaining
      business model. DISCUSSION: Based on the principles identified, a roadmap for
      national CDS knowledge sharing was developed through the ONC's Advancing CDS
      initiative. CONCLUSION: The study findings may serve as a useful guide for
      ongoing activities by the ONC and others to establish a national framework for
      sharing CDS knowledge and improving clinical care.

PMID- 22865672
TI  - Two open access, high-quality datasets from anesthetic records.
AB  - OBJECTIVE: To provide a set of high-quality time-series physiologic and event
      data from anesthetic cases formatted in an easy-to-use structure. MATERIALS AND
      METHODS: With ethics committee approval, data from surgical operations under
      general anesthesia were collected, including physiologic data, drug
      administrations, events, and clinicians' comments. These data were de-identified,
      formatted in a combined CSV/XML structure and made publicly available. RESULTS:
      Two separate datasets were collected containing physiologic time-series data and
      time-stamped events for 34 patients. For 20 patients, the data included 400
      physiologic signals collected over 20 h, 274 events, and 597 drug
      administrations. For 14 patients, the data included 23 physiologic signals
      collected over 69 h, with 286 time stamped comments. DISCUSSION: Data reuse
      potentially saves significant time and financial costs. However, there are few
      high-quality repositories for accessible physiologic data and clinical
      interventions from surgical cases. De-identifying records assists with overcoming
      problems of privacy and storing the data in a format which is easily manipulated
      with computing resources facilitates access by the wider research community. It
      is hoped that additional high-quality data will be added. Future work includes
      developing tools to explore and visualize the data more efficiently, and
      establishing quality control measures. CONCLUSION: An approach to collecting and
      storing high-quality datasets from surgical operations under anesthesia such that
      they can be easily accessed by others for use in research has been demonstrated.

PMID- 22865673
TI  - Hybrid mesoporous-silica materials functionalized by Pt(II) complexes:
      correlation between the spatial distribution of the active center,
      photoluminescence emission, and photocatalytic activity.
AB  - [Pt(tpy)Cl]Cl (tpy: terpyridine) was successfully anchored to a series of
      mesoporous-silica materials that were modified with (3
      aminopropyl)triethoxysilane with the aim of developing new inorganic-organic
      hybrid photocatalysts. Herein, the relationship between the luminescence
      characteristics and photocatalytic activities of these materials is examined as a
      function of Pt loading to define the spatial distribution of the Pt complex in
      the mesoporous channel. At low Pt loading, the Pt complex is located as an
      isolated species and exhibits strong photoluminescence emission at room
      temperature owing to metal-to-ligand charge-transfer ((3)MLCT) transitions (at
      about 530 nm). Energy- and/or electron-transfer from (3)MLCT to O(2) generate
      potentially active oxygen species, which are capable of promoting the selective
      photooxidation of styrene derivatives. On the other hand, short Pt...Pt
      interactions are prominent at high loading and the metal-metal-to-ligand charge
      transfer ((3)MMLCT) transition is at about 620 nm. Such Pt complexes, which are
      situated close to each other, efficiently catalyze H(2)-evolution reactions in
      aqueous media in the presence of a sacrificial electron donor (EDTA) under
      visible-light irradiation. This study also investigates the effect of
      nanoconfinement on anchored guest complexes by considering the differences
      between the pore dimensions and structures of mesoporous-silica materials.

PMID- 22865674
TI  - Enhanced catalytic activity for methanol electro-oxidation of uniformly dispersed
      nickel oxide nanoparticles-carbon nanotube hybrid materials.
AB  - Highy crystalline NiO nanoparticles are uniformly grown on the walls of carbon
      nanotubes (CNTs) by atomic layer deposition (ALD) at moderate temperature.Their
      size and stoichiometry are controlled by the ALD process parameters. The obtained
      NiO/CNT hybrids exhibit excellent performance in the electro-oxidation of
      methanol. 

PMID- 22865675
TI  - Xanthones from the stems of Cratoxylum cochinchinense.
AB  - Four new xanthones, 1-methoxy-3,7,8-trihydroxyxanthone (1), 1-methoxy-4,7,8
      trihydroxyxanthone (2), 1-methoxy-4,7-dihydroxyxanthone (3), and 1,4-dimethoxy
      2,7-dihydroxyxanthone (4) were isolated from the stems of Cratoxylum
      cochinchinense along with four known xanthones (5-8). The structures of new
      compounds were determined by extensive spectroscopic analyses, mainly 1D and 2D
      NMR and HRESIMS data.

PMID- 22865676
TI  - Short-time cold dry air exposure: a useful diagnostic tool for nasal
      hyperresponsiveness.
AB  - OBJECTIVES/HYPOTHESIS: Demonstration of nasal hyperreactivity (NHR) in allergic
      and nonallergic rhinitis remains a diagnostic challenge because of the lack of a
      clinically attractive protocol with high sensitivity and specificity. Our aim was
      to evaluate the feasibility of a shortened cold dry air (CDA) provocation
      protocol for the diagnosis of NHR in patients with allergic rhinitis (AR) and
      idiopathic rhinitis (IR). STUDY DESIGN: Twelve AR patients, 12 IR patients, and
      12 controls were exposed to air at -10 degrees C and <10% humidity for 15
      minutes. METHODS: Nasal symptoms were subjectively evaluated by visual analogue
      scale (VAS), and nasal obstruction was objectively measured by peak nasal
      inspiratory flow (PNIF) before and after CDA exposure. NHR was defined as a drop
      in PNIF larger than 20% from baseline upon CDA challenge. RESULTS: Nasal CDA
      exposure induced nasal obstruction in AR and IR patients but not in controls. The
      VAS for nasal obstruction increased significantly in IR patients (post-CDA: 9.1
      cm [6.9, 9.7] vs. pre-CDA: 5.5 cm [5.0, 8.9], P = .004) as well as in AR patients
      (post-CDA: 5.0 cm [1.3, 6.6] vs. pre-CDA: 0.8 cm [0.0, 1.7], P = .001). PNIF
      values showed a significant decrease in the AR (post-CDA: 50.0 L/min [37.5, 97.5]
      vs. pre-CDA: 95.0 L/min [52.5, 127.5], P = .002) and IR (post-CDA: 75.0 L/min
      [47.5, 102.5] vs. pre-CDA: 100.0 L/min [67.5, 130.0], P = .002) group after CDA
      provocation, which was not observed in the controls (P = 1.000). The sensitivity
      and specificity of CDA provocation for diagnosis of NHR were 66.7% and 100%,
      respectively, for both IR and AR. In contrast to nasal obstruction, rhinorrhea
      and sneezing were not induced by CDA exposure. CONCLUSIONS: This study
      demonstrates that a short nasal CDA exposure is a reliable method for the
      diagnosis of NHR in rhinitis patients, with a high sensitivity and specificity.

PMID- 22865677
TI  - Characterizations of additive manufactured porous titanium implants.
AB  - This article describes physical, chemical, and mechanical characterizations of
      porous titanium implants made by an additive manufacturing method to gain insight
      into the correlation of process parameters and final physical properties of
      implants used in orthopedics. For the manufacturing chain, the powder metallurgy
      technology was combined with the additive manufacturing to fabricate the porous
      structure from the pure tanium powder. A 3D printing machine was employed in this
      study to produce porous bar samples. A number of physical parameters such as
      titanium powder size, polyvinyl alcohol (PVA) amount, sintering temperature and
      time were investigated to control the mechanical properties and porosity of the
      structures. The produced samples were characterized through porosity and
      shrinkage measurements, mechanical compression test and scanning electron
      microscopy (SEM). The results showed a level of porosity in the samples in the
      range of 31-43%, which is within the range of the porosity of the cancelluous
      bone and approaches the range of the porosity of the cortical bone. The results
      of the mechanical test showed that the compressive strength is in the wide range
      of 56-509 MPa implying the effect of the process parameters on the mechanical
      strengths. This technique of manufacturing of Ti porous structures demonstrated a
      low level of shrinkage with the shrinkage percentage ranging from 1.5 to 5%.

PMID- 22865678
TI  - Principles of research: 1959.

PMID- 22865679
TI  - Aptamer-based affinity labeling of proteins.
AB  - A most able label: Labeled aptamers can be cross-linked to their target
      structures in a light-dependent and highly specific manner as a result of a new
      strategy termed aptamer-based affinity labeling (ABAL) of proteins. The aptamer
      protein complexes can be enriched in vitro, from a cellular lysate and from the
      surface of living cells, opening new ways to study aptamer interactions in
      biological contexts.

PMID- 22865680
TI  - Accelerating three-dimensional molecular cardiovascular MR imaging using
      compressed sensing.
AB  - PURPOSE: To accelerate the acquisition of three-dimensional (3D) high-resolution
      cardiovascular molecular MRI by using Compressed Sensing (CS) reconstruction.
      MATERIALS AND METHODS: Molecular MRI is an emerging technique for the early
      assessment of cardiovascular disease. This technique provides excellent soft
      tissue differentiation at a molecular and cellular level using target-specific
      contrast agents (CAs). However, long scan times are required for 3D molecular
      MRI. Parallel imaging can be used to speed-up these acquisitions, but hardware
      considerations limit the maximum acceleration factor. This limitation is
      important in small-animal studies, where single-coils are commonly used. Here we
      exploit the sparse nature of molecular MR images, which are characterized by
      localized and high-contrast biological target-enhancement, to accelerate data
      acquisition. CS was applied to detect: (a) venous thromboembolism and (b)
      coronary injury and aortic vessel wall in single- and multiple-coils
      acquisitions, respectively. RESULTS: Retrospective undersampling showed good
      overall image quality with accelerations up to four for thrombus and aortic
      images, and up to three for coronary artery images. For higher acceleration
      factors, features with high CA uptake were still well recovered while low
      affinity targets were less preserved with increased CS undersampling artifacts.
      Prospective undersampling was performed in an aortic image with acceleration of
      two, showing good contrast and well-defined tissue boundaries in the contrast
      enhanced regions. CONCLUSION: We demonstrate the successful application of CS to
      preclinical molecular MR with target specific gadolinium-based CAs using
      retrospective (accelerations up to four) and prospective (acceleration of two)
      undersampling.

PMID- 22865681
TI  - Induction of neuronal phenotypes from NG2+ glial progenitors by inhibiting
      epidermal growth factor receptor in mouse spinal cord injury.
AB  - Besides neural stem cells, some glial cells, such as GFAP+ cells, radial glia,
      and oligodendrocyte progenitor cells can produce neuronal cells. Attractively,
      NG2+ glial progenitors exhibit lineage plasticity, and they rapidly proliferate
      and differentiate in response to central nervous system (CNS) injuries. These
      attributes of NG2+ glial progenitors make them a promising source of neurons.
      However, the potential of neuronal regeneration from NG2+ glial progenitors in
      CNS pathologies remains to be investigated. In this study, we showed that
      antagonizing epidermal growth factor receptor (EGFR) function with EGFR inhibitor
      caused a significant number of proliferative NG2+ glial progenitors to acquire
      neuronal phenotypes in contusive spinal cord injury (SCI), which presumably led
      to an accumulation of newly generated neurons and contributed to the improved
      neural behavioral performance of animals. In addition, the neuronal
      differentiation of glial progenitors induced by EGFR inhibitor was further
      confirmed with two different cell lines either in vitro or through ex vivo
      transplantation experiment. The inhibition of EGFR signaling pathway under the
      gliogenic conditions could induce these cells to acquire neuronal phenotypes.
      Furthermore, we find that the Ras-ERK axis played a key role in neuronal
      differentiation of NG2+ glial progenitors upon EGFR inhibition. Taken together,
      our studies suggest that the EGFR inhibitor could promote neurogenesis post SCI,
      mainly from the NG2+ glial progenitors. These findings support the possibility of
      evoking endogenous neuronal replacement from NG2+ glial progenitors and suggest
      that EGFR inhibition may be beneficial to CNS trauma.

PMID- 22865682
TI  - Methods for predicting the rate constant for uptake of organic chemicals from
      water by fish.
AB  - Bioaccumulation is an important information requirement for chemicals risk
      assessment. The most widely used test guideline for measuring bioaccumulation in
      fish is the OECD 305 test guideline and, in the future, it is likely to include a
      dietary exposure method for substances that are difficult to test by the more
      usual aqueous exposure route. This new method results in a biomagnification
      factor (BMF), whereas for regulatory purposes a bioconcentration factor (BCF) is
      often required. Therefore, being able to estimate a BCF quantitatively from the
      data generated in the dietary study would meet an accepted regulatory need. The
      information generated by the dietary study includes the depuration rate constant.
      To use these data to estimate a BCF, an estimate of the rate constant for uptake
      from water is needed, allowing a kinetic BCF to be calculated. The present study
      considers and tests methods that are currently available for predicting uptake
      rate constants from water using a database of bioconcentration data. A number of
      methods were found to perform similarly when tested with substances with a log
      K(OW) range of approximately 3.5 to 8.2. The uncertainty in the estimated uptake
      rate constant was relatively large, however, even for the best performing
      methods.

PMID- 22865683
TI  - Synergistic targeting of cancer and associated angiogenesis using triple-targeted
      dual-drug silica nanoformulations for theragnostics.
AB  - The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica
      nanoparticles, functionalized with triple targeting ligands specific towards
      cancer and neoangiogenesis simultaneously, are discussed. This synergized, high
      precision, multitarget concept culminates in an elevated uptake of nanoparticles
      by cancer and angiogenic cells with amplified proficiency, thereby imparting
      superior therapeutic efficacy against breast cancer cells and completely
      disabling the migration and angiogenic sprouting ability of activated endothelial
      cells. The exceptional multimodal efficiency achieved by this single therapeutic
      nanoformulation holds promise for the synergistic targeting and treatment of the
      yet elusive cancer and its related angiogenesis in a single, lethal shot. 

PMID- 22865684
TI  - Formal synthesis of dictyostatin and synthesis of two dictyostatin analogues.
AB  - A formal convergent synthesis of dictyostatin from (R)-Roche ester is described.
      Synthetic highlights include a Ni-catalyzed Nozaki-Hiyama-Kishi coupling between
      an aldehyde and a Z vinyl iodide to assemble the two main fragments, a
      diastereoselective Myers alkylation, a stereoselective Evans aldolization, two
      asymmetric Duthaler crotyltitanations, and a stereoselective Pd-catalyzed
      Marshall allenylindium addition to install the stereogenic centers of
      dictyostatin. The synthesis of (9R)-epi-dictyostatin and a new ring-contracted
      dictyostatin isomer were also achieved.

PMID- 22865685
TI  - Heterochronic protein expression patterns in the developing embryonic chick
      cerebellum.
AB  - The advantages of the embryonic chick as a model for studying neural development
      range from the relatively low cost of fertilized eggs to the rapid rate of
      development. We investigated in ovo cerebellar development in the chick, which
      has a nearly identical embryonic period as the mouse (19-22 days). We focused on
      three antigens: Calbindin (CB), Zebrin II (ZII), and Calretinin (CR), and our
      results demonstrate asynchronous expression patterns during cerebellar
      development. Presumptive CB+ Purkinje cells are first observed at embryonic day
      (E)10 in clusters in posterior cerebellum. At E12, corresponding with global
      expression of CB across the cerebellum, Purkinje cells began to express ZII. By
      E14-E16, Purkinje cells disperse into a monolayer and develop a pattern of
      alternating immunopositive and immunonegative ZII stripes. CR is initially
      expressed by clusters of presumptive Purkinje cells in the nodular zone at E8.
      However, this expression is transient and at later stages, CR is largely confined
      to the granule and molecular layers. Before hatch (E18-E20), Purkinje cells adopt
      a morphologically mature phenotype with complex dendritic arborizations.
      Comparing this data to that seen in mice, we found that the sequence of Purkinje
      cell formation, protein expression, and development is similar in both species,
      but these events consistently begin ~5-7 days earlier in the precocial chick
      cerebellum, suggesting an important role for heterochrony in neurodevelopment.

PMID- 22865686
TI  - Green nanoemulsion-laden glyphosate isopropylamine formulation in suppressing
      creeping foxglove (A. gangetica), slender button weed (D. ocimifolia) and buffalo
      grass (P. conjugatum).
AB  - BACKGROUND: Pesticides are developed with carriers to improve their
      physicochemical properties and, accordingly, the bioefficacy of the applied
      formulation. For foliar-applied herbicide, generally less than 0.1% of the active
      ingredient reaching the target site could reduce pesticide performance. Recently,
      a carrier of nanoemulsion consisting of oil, surfactant and water, with a
      particle size of less than 200 nm, has been shown to enhance drug permeability
      for skin penetration in pharmaceutical delivery systems. In the present work, the
      aim was to formulate a water-soluble herbicide, glyphosate isopropylamine (IPA),
      using a green nanoemulsion system for a biological activity study against the
      weeds creeping foxglove, slender button weed and buffalo grass. RESULTS: The
      nanoemulsion formulations displayed a significantly lower spray deposition on
      creeping foxglove (2.9-3.5 ng cm(-2) ), slender button weed (2.6-2.9 ng cm(-2) )
      and buffalo grass (1.8-2.4 ng cm(-2) ) than Roundup((r)) (3.7-5.1 ng cm(-2) ).
      The visible injury rates of weeds treated with the nanoemulsion formulations were
      statistically equivalent to those relating to Roundup((r)) at 14 days after
      treatment, with a control range of 86.67-96.67%. CONCLUSION: It was hypothesised
      that the significant difference in spray deposition with equal injury rates can
      be attributed to enhanced bioactivity of the nanoemulsion formulations. This
      initial discovery could be the platform for developing better penetration of
      agrochemical formulations in the future.

PMID- 22865687
TI  - (1) H and (13) C NMR assignments of four series bioactive pyrido[4,3-d]pyrimidine
      derivatives.
AB  - The complete (1) H and (13) C NMR assignments of four series pyrido[4,3
      d]pyrimidine derivatives were achieved by combination of one and two-dimensional
      NMR experiments, and the NMR signals of these compounds were analyzed and
      compared.

PMID- 22865688
TI  - Minimally invasive approach to laryngeal cleft.
AB  - Laryngeal cleft is a rare congenital anomaly that is recently being diagnosed
      with increased frequency. The objective of this report is to present a
      comprehensive description of endoscopic laser repair of a laryngeal cleft, using
      both the carbon dioxide (CO(2)) laser via a micromanipulator (Carl Zeiss
      Microimaging Inc., Thornwood, NY) and the flexible CO(2) laser fiber (OmniGuide,
      Inc.; Cambridge, MA), from both an anesthesia and surgical perspective.
      Laryngoscope, 2013.

PMID- 22865689
TI  - Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to
      produce prostaglandin E2 that directs stimulated macrophages into an anti
      inflammatory phenotype.
AB  - Culturing cells in three dimension (3D) provides an insight into their
      characteristics in vivo. We previously reported that human mesenchymal
      stem/stromal cells (hMSCs) cultured as 3D spheroids acquire enhanced anti
      inflammatory properties. Here, we explored the effects of hMSC spheroids on
      macrophages that are critical cells in the regulation of inflammation.
      Conditioned medium (CM) from hMSC spheroids inhibited lipopolysaccharide
      stimulated macrophages from secreting proinflammatory cytokines TNFalpha, CXCL2,
      IL6, IL12p40, and IL23. CM also increased the secretion of anti-inflammatory
      cytokines IL10 and IL1ra by the stimulated macrophages, and augmented expression
      of CD206, a marker of alternatively activated M2 macrophages. The principal anti
      inflammatory activity in CM had a small molecular weight, and microarray data
      suggested that it was prostaglandin E2 (PGE2). This was confirmed by the
      observations that PGE2 levels were markedly elevated in hMSC spheroid-CM, and
      that the anti-inflammatory activity was abolished by an inhibitor of
      cyclooxygenase-2 (COX-2), a silencing RNA for COX-2, and an antibody to PGE2. The
      anti-inflammatory effects of the PGE2 on stimulated macrophages were mediated by
      the EP4 receptor. Spheroids formed by human adult dermal fibroblasts produced low
      levels of PGE2 and displayed negligible anti-inflammatory effects on stimulated
      macrophages, suggesting the features as unique to hMSCs. Moreover, production of
      PGE2 by hMSC spheroids was dependent on the activity of caspases and NFkappaB
      activation in the hMSCs. The results indicated that hMSCs in 3D-spheroid cultures
      are self-activated, in part by intracellular stress responses, to produce PGE2
      that can change stimulated macrophages from a primarily proinflammatory M1
      phenotype to a more anti-inflammatory M2 phenotype.

PMID- 22865691
TI  - Silk fibroin particles as templates for mineralization of calcium-deficient
      hydroxyapatite.
AB  - Silk fibroin particles prepared by phase separation with polyethylene oxide were
      coated with calcium-deficient hydroxyapatite (CDHA) crystals under various pH
      conditions. For different pH values, the growth and the morphology of CDHA
      crystals on the surface of silk fibroin particles were investigated in detail by
      zeta potential analysis, scanning electron microscopy, transmission electron
      microscopy, and X-ray diffraction techniques. Negative charges formed by
      deprotonation of the functional groups on the surface of silk fibroin particles
      at high pH lead to an increase of binding affinity between the calcium ions of
      the CDHA crystals and the functional groups of the silk fibroin particles.
      Consequently, the generation of many CDHA crystals was promoted to deposit on the
      surface of silk fibroin particles at a high pH value.

PMID- 22865690
TI  - Proinflammatory cytokine regulation of cyclic AMP-phosphodiesterase 4 signaling
      in microglia in vitro and following CNS injury.
AB  - Cyclic AMP suppresses immune cell activation and inflammation. The positive
      feedback loop of proinflammatory cytokine production and immune activation
      implies that cytokines may not only be regulated by cyclic AMP but also
      conversely regulate cyclic AMP. This study examined the effects of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta on cyclic AMP-phosphodiesterase
      (PDE) signaling in microglia in vitro and after spinal cord injury (SCI) or
      traumatic brain injury (TBI). TNF-alpha or IL-1beta stimulation produced a
      profound reduction (>90%) of cyclic AMP within EOC2 microglia from 30 min that
      then recovered after IL-1beta but remained suppressed with TNF-alpha through 24
      h. Cyclic AMP was also reduced in TNF-alpha-stimulated primary microglia, albeit
      to a lesser extent. Accompanying TNF-alpha-induced cyclic AMP reductions, but not
      IL-1beta, was increased cyclic AMP-PDE activity. The role of PDE4 activity in
      cyclic AMP reductions was confirmed by using Rolipram. Examination of pde4 mRNA
      revealed an immediate, persistent increase in pde4b with TNF-alpha; IL-1beta
      increased all pde4 mRNAs. Immunoblotting for PDE4 showed that both cytokines
      increased PDE4A1, but only TNF-alpha increased PDE4B2. Immunocytochemistry
      revealed PDE4B nuclear translocation with TNF-alpha but not IL-1beta. Acutely
      after SCI/TBI, where cyclic AMP levels are reduced, PDE4B was localized to
      activated OX-42(+) microglia; PDE4B was absent in OX-42(+) cells in uninjured
      spinal cord/cortex or inactive microglia. Immunoblotting showed PDE4B2 up
      regulation from 24 h to 1 wk post-SCI, the peak of microglia activation. These
      studies show that TNF-alpha and IL-1beta differentially affect cyclic AMP-PDE
      signaling in microglia. Targeting PDE4B2 may be a putative therapeutic direction
      for reducing microglia activation in CNS injury and neurodegenerative diseases.

PMID- 22865692
TI  - Hexaphyrin fused to two anthracenes.
AB  - Gold standard: A bis(Au(III)) complex containing the title compound was prepared
      and characterized (see scheme; DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone,
      Tf=trifluoromethanesulfonyl). Owing to the effective conjugative network over the
      flat and elongated rectangular molecular frame, this complex displays a
      remarkably red-shifted and sharp Q-band-like band at 1467 nm, multiple reversible
      redox potentials, and a large TPA cross-section value.

PMID- 22865693
TI  - The benefits of herbicide-resistant crops.
AB  - Since 1996, genetically modified herbicide-resistant crops, primarily glyphosate
      resistant soybean, corn, cotton and canola, have helped to revolutionize weed
      management and have become an important tool in crop production practices.
      Glyphosate-resistant crops have enabled the implementation of weed management
      practices that have improved yield and profitability while better protecting the
      environment. Growers have recognized their benefits and have made glyphosate
      resistant crops the most rapidly adopted technology in the history of
      agriculture. Weed management systems with glyphosate-resistant crops have often
      relied on glyphosate alone, have been easy to use and have been effective,
      economical and more environmentally friendly than the systems they have replaced.
      Glyphosate has worked extremely well in controlling weeds in glyphosate-resistant
      crops for more than a decade, but some key weeds have evolved resistance, and
      using glyphosate alone has proved unsustainable. Now, growers need to renew their
      weed management practices and use glyphosate with other cultural, mechanical and
      herbicide options in integrated systems. New multiple-herbicide-resistant crops
      with resistance to glyphosate and other herbicides will expand the utility of
      existing herbicide technologies and will be an important component of future weed
      management systems that help to sustain the current benefits of high-efficiency
      and high-production agriculture.

PMID- 22865694
TI  - Donor-pi-acceptors containing the 10-(1,3-dithiol-2-ylidene)anthracene unit for
      dye-sensitized solar cells.
AB  - Two donor-acceptor molecular tweezers incorporating the 10-(1,3-dithiol-2
      ylidene)anthracene unit as donor group and two cyanoacrylic units as
      accepting/anchoring groups are reported as metal-free sensitizers for dye
      sensitized solar cells. By changing the phenyl spacer with 3,4
      ethylenedioxythiophene (EDOT) units, the absorption spectrum of the sensitizer is
      red-shifted with a corresponding increase in the molar absorptivity. Density
      functional calculations confirmed the intramolecular charge-transfer nature of
      the lowest-energy absorption bands. The new dyes are highly distorted from
      planarity and are bound to the TiO(2) surface through the two anchoring groups in
      a unidentate binding form. A power-conversion efficiency of 3.7% was obtained
      with a volatile CH(3)CN-based electrolyte, under air mass 1.5 global sunlight.
      Photovoltage decay transients and ATR-FTIR measurements allowed us to understand
      the photovoltaic performance, as well as the surface binding, of these new
      sensitizers.

PMID- 22865695
TI  - Background-free solution boron NMR spectroscopy.
AB  - The appearance of background signals arising from the NMR probe and tube is a
      well-known problem of boron NMR spectroscopy. Background suppression may be
      achieved by using DEPTH, which increases the signal-to-background (S/B) ratio.
      Although, the quality of such spectra is often adequate, but in the case of rapid
      relaxation broadened resonances (T(1)  < 1 ms), the residual background signals
      may still hamper the interpretation of the spectra. It was observed that the
      background signals are practically invisible in solution (10) B NMR. The unusual
      isotopic effect on the (S/B) ratio was interpreted as an inherent consequence of
      the integer versus half-integer spin of (10) B and (11) B, respectively. The
      practicability of (10/11) B NMR was compared for a selected set of boron
      compounds covering the typical range of (S/B) ratio. The application of (11) B is
      more favourable than (10) B as long as it is possible to achieve the desired
      spectral quality by using DEPTH. Otherwise, the 'background-free' appearance of
      (10) B NMR spectra makes (10) B a reasonable alternative of (11) B DEPTH. This
      was found typical for compounds having relaxation broadened resonances. The
      variable temperature (VT) NMR study of an adduct formation process was also
      presented here as an example of the advantage of (10) B over (11) B.

PMID- 22865696
TI  - Susceptibility phase imaging with improved image contrast using moving window
      phase gradient fitting and minimal filtering.
AB  - PURPOSE: To enhance image contrast in susceptibility phase imaging using a new
      method of background phase removal. MATERIALS AND METHODS: A background phase
      removal method is proposed that uses the spatial gradient of the raw phase image
      to perform a moving window third-order local polynomial estimation and correction
      of the raw phase image followed by minimal high pass filtering. The method is
      demonstrated in simulation, 10 healthy volunteers, and 5 multiple sclerosis
      patients in comparison to a standard phase filtering approach. RESULTS: Compared
      to standard phase filtering, the new method increased phase contrast with local
      background tissue in subcortical gray matter, cortical gray matter, and multiple
      sclerosis lesions by 67% +/- 33%, 13% +/- 7%, and 48% +/- 19%, respectively (95%
      confidence interval). In addition, the new method removed more phase wraps in
      areas of rapidly changing background phase. CONCLUSION: Local phase gradient
      fitting combined with minimal high pass filtering provides better tissue
      depiction and more accurate phase quantification than standard filtering.

PMID- 22865697
TI  - Atypical visuospatial processing in autism: insights from functional connectivity
      analysis.
AB  - Atypical visuospatial processing is commonly described in autism spectrum
      disorders (ASDs); however the specific neurobiological underpinnings of this
      phenomenon are poorly understood. Given the extensive evidence suggesting ASDs
      are characterized by abnormal neural connectivity, this study aimed to
      investigate network connectivity during visuospatial processing in ASD. Twenty
      two males with ASD without intellectual disability and 22 individually matched
      controls performed a mental rotation task during functional magnetic resonance
      imaging (MRI) in which two rotated stimuli were judged to be same ("Same Trials")
      or mirror-imaged ("Mirror Trials"). Behavioral results revealed a relative
      advantage of mental rotation in the ASD group-controls were slower responding to
      the more difficult Mirror Trials than Same Trials whereas the ASD group completed
      Mirror Trials and Same-trials at similar speeds. In the ASD group, brain activity
      was reduced in frontal, temporal, occipital, striatal, and cerebellar regions
      and, consistent with previous literature, functional connectivity between a
      number of brain regions was reduced. However, some connections appeared to be
      conserved and were recruited in a qualitatively different way by the two groups.
      As task difficulty increased (on Mirror Trials), controls tended to increase
      connections between certain brain regions, whereas the ASD group appeared to
      suppress connections between these regions. There was an interesting exception to
      this pattern in the visual cortex, a finding that may suggest an advantage in
      early visual perceptual processing in ASD. Overall, this study has identified a
      relative advantage in mental rotation in ASD that is associated with aberrant
      neural connectivity and that may stem from enhanced visual perceptual processing.

PMID- 22865698
TI  - Derivation of screening benchmarks for dietary methylmercury exposure for the
      common loon (Gavia immer): rationale for use in ecological risk assessment.
AB  - The current understanding of methylmercury (MeHg) toxicity to avian species has
      improved considerably in recent years and indicates that exposure to
      environmentally relevant concentrations of MeHg through the diet can adversely
      affect various aspects of avian health, reproduction, and survival. Because fish
      eating birds are at particular risk for elevated MeHg exposure, the authors
      surveyed the available primary and secondary literature to summarize the effects
      of dietary MeHg on the common loon (Gavia immer) and to derive ecologically
      relevant toxic thresholds for dietary exposure to MeHg in fish prey. After
      considering the available data, the authors propose three screening benchmarks of
      0.1, 0.18, and 0.4 ug g(-1) wet weight MeHg in prey fish. The lowest benchmark
      (0.1 ug g(-1) wet wt) is the threshold for adverse behavioral impacts in adult
      loons and is close to the empirically determined no observed adverse effects
      level for subclinical effects observed in captive loon chicks. The remaining
      benchmarks (0.18 and 0.4 ug g(-1) wet wt) correspond to MeHg levels in prey fish
      associated with significant reproductive impairment and reproductive failure in
      wild adult loons. Overall, these benchmarks incorporate recent findings and
      reviews of MeHg toxicity in aquatic fish-eating birds and provide the basis for a
      national ecological risk assessment for Hg and loons in Canada.

PMID- 22865699
TI  - Waiting for thyroid surgery: a study of psychological morbidity and determinants
      of health associated with long wait times for thyroid surgery.
AB  - OBJECTIVES: Patients with thyroid pathology tend have longer surgical wait times.
      Uncertainty during this wait can have negative psychologically impact. This study
      aims to determine the degree of psychological morbidity in patients waiting for
      thyroid surgery. STUDY DESIGN: Prospectively assessing patients pre- and
      postoperative psychological morbidity (level 2c). METHODS: Patients waiting for
      thyroidectomy were mailed a sociodemographic and four psychological morbidity
      questionnaires: Impact of Events Scale-Revised (IES-R), Illness Intrusiveness
      Ratings Scale (IIRS), Perceived Stress Scale (PSS) and Hospital Anxiety and
      Depression Scale (HADS). We assessed whether anxiety was related to length of
      wait and a number of clinical/sociodemographic factors. RESULTS: We achieved a
      53% response rate over a 3-year period, with 176 patients providing complete
      preoperative data; and 74 (42%) completed postoperative data. The average age was
      53 (+/- 12) years; 82% were female. Respondents with a suspicious or known
      malignancy waited an average of 107 days while those with benign neoplastic
      biopsies waited an average of 218 days for thyroidectomy. Respondents reported
      substantial psychological morbidity with high IES-R, IIRS, PSS, and HADS scores.
      There was no significant association between psychological morbidity and wait
      times, clinical or sociodemographic factors. Postoperative anxiety decreased
      significantly in all psychological morbidity measures except for the IIRS.
      CONCLUSIONS: Patients waiting for thyroid surgery have mild to moderate
      psychological morbidity and long wait times for surgery. These appear not to be
      related. Psychological morbidity decreases after surgery. Reducing wait time can
      potentially reduce the time that patients have to live with unnecessary stress
      and anxiety.

PMID- 22865700
TI  - Integrating genetic association, genetics of gene expression, and single
      nucleotide polymorphism set analysis to identify susceptibility Loci for type 2
      diabetes mellitus.
AB  - Large-scale genome-wide association studies (GWAS) have identified over 40
      genomic regions significantly associated with type 2 diabetes mellitus. However,
      GWAS results are not always straightforward to interpret, and linking these loci
      to meaningful disease etiology is often difficult without extensive follow-up
      studies. The authors expanded on previously reported type 2 diabetes mellitus
      GWAS from the nested case-control studies of 2 prospective US cohorts by
      incorporating expression single nucleotide polymorphism (SNP) information and
      applying SNP set enrichment analysis to identify sets of SNPs associated with
      genes that could provide further biologic insight to traditional genome-wide
      analysis. Using data collected between 1989 and 1994 in these previous studies to
      form a nested case-control study, the authors found that 3 of the most
      significantly associated SNPs to type 2 diabetes mellitus in their study are
      expression SNPs to the lymphocyte antigen 75 gene (LY75), the ubiquitin-specific
      peptidase 36 gene (USP36), and the phosphatidylinositol transfer protein,
      cytoplasmic 1 gene (PITPNC1). SNP set enrichment analysis of the GWAS results
      identified enrichment for expression SNPs to the macrophage-enriched module and
      the Gene Ontology (GO) biologic process fat cell differentiation human, which
      includes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2
      diabetes mellitus-associated genes. Integrating genome-wide association, gene
      expression, and gene set analysis may provide valuable biologic support for
      potential type 2 diabetes mellitus susceptibility loci and may be useful in
      identifying new targets or pathways of interest for the treatment and prevention
      of type 2 diabetes mellitus.

PMID- 22865701
TI  - Genome-wide linkage and positional association study of blood pressure response
      to dietary sodium intervention: the GenSalt Study.
AB  - The authors conducted a genome-wide linkage scan and positional association
      analysis to identify the genetic determinants of salt sensitivity of blood
      pressure (BP) in a large family-based, dietary-feeding study. The dietary
      intervention was conducted among 1,906 participants in rural China (2003-2005). A
      7-day low-sodium intervention was followed by a 7-day high-sodium intervention.
      Salt sensitivity was defined as BP responses to low- and high-sodium
      interventions. Signals of the logarithm of the odds to the base 10 (LOD >= 3)
      were detected at 33-42 centimorgans of chromosome 2 (2p24.3-2p24.1), with a
      maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium
      intervention. LOD scores were 2.35-2.91 for mean arterial pressure (MAP) and 0.80
      1.49 for systolic blood pressure responses in this region, respectively.
      Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786
      (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene
      (FAM84A)) in the linkage region was significantly associated with diastolic blood
      pressure (P = 0.0007) and MAP responses (P = 0.0007), and SNP rs16983422 (2.8
      kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated
      with diastolic blood pressure (P = 0.005) and MAP responses (P = 0.005). An
      additive interaction between SNPs rs11674786 and rs16983422 was observed, with P
      = 7.00 * 10(-5) and P = 7.23 * 10(-5) for diastolic blood pressure and MAP
      responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1
      might harbor functional variants for the salt sensitivity of BP.

PMID- 22865702
TI  - Dual lineage-specific expression of Sox17 during mouse embryogenesis.
AB  - Sox17 is essential for both endoderm development and fetal hematopoietic stem
      cell (HSC) maintenance. While endoderm-derived organs are well known to originate
      from Sox17-expressing cells, it is less certain whether fetal HSCs also originate
      from Sox17-expressing cells. By generating a Sox17(GFPCre) allele and using it to
      assess the fate of Sox17-expressing cells during embryogenesis, we confirmed that
      both endodermal and a part of definitive hematopoietic cells are derived from
      Sox17-positive cells. Prior to E9.5, the expression of Sox17 is restricted to the
      endoderm lineage. However, at E9.5 Sox17 is expressed in the endothelial cells
      (ECs) at the para-aortic splanchnopleural region that contribute to the formation
      of HSCs at a later stage. The identification of two distinct progenitor cell
      populations that express Sox17 at E9.5 was confirmed using fluorescence-activated
      cell sorting together with RNA-Seq to determine the gene expression profiles of
      the two cell populations. Interestingly, this analysis revealed differences in
      the RNA processing of the Sox17 mRNA during embryogenesis. Taken together, these
      results indicate that Sox17 is expressed in progenitor cells derived from two
      different germ layers, further demonstrating the complex expression pattern of
      this gene and suggesting caution when using Sox17 as a lineage-specific marker.

PMID- 22865703
TI  - Synthesis of galactosylated chitosan/5-fluorouracil nanoparticles and its
      characteristics, in vitro and in vivo release studies.
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. We found that when 5-FU
      and GC were mixed at the mass ratio of 10:1, the nanoparticle reached a maximum
      encapsulation efficiency of 81.82% +/- 5.32%, with a drug loading of 6.12% +/-
      1.36%, a particle size of 35.19 +/- 9.50 nm, and a Zeta potential of +10.34 +/-
      1.43 mV. The GC/5-FU nanoparticle is a sustained release system, whose anticancer
      effects were shown to be dose and time dependent, with a higher cytotoxicity to
      hepatic cancer than to other cell types. The distribution of GC/5-FU in vivo
      revealed the greatest accumulation in the hepatic cancer tissues, with an 8.69-,
      23.35-, 79.96-, and 85.15-fold increase when compared to normal liver tissue,
      kidney, heart and blood, respectively, suggesting that the hepatic cell was the
      target of the nanoparticles. 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 to 5-FU treatment alone. Flow cytometry
      revealed that compared to 5-FU, GC/5-FU caused higher rates of G0-G1 arrest and
      apoptosis in hepatic cancer cells.

PMID- 22865704
TI  - The medial habenula contains a specific nonstellate subtype of astrocyte
      expressing the ectonucleotidase NTPDase2.
AB  - ATP-mediated synaptic transmission represents the only transmitter-gated Ca(2+)
      entry pathway in neurons of the rodent medial habenula. In addition to direct
      purinergic receptor-mediated synaptic inputs, the medial habenula contains
      purinergic systems that modulate synaptic transmission. Purinergic signaling is
      modulated or terminated by ectonucleotidase, nucleotide-hydrolyzing enzymes of
      the cell surface. Here we identify the major ectonucleotidase responsible for the
      hydrolysis of extracellular ATP in the mouse medial habenula as ectonucleoside
      triphosphate diphosphohydrolase 2 (NTPDase2), using immunostaining and enzyme
      histochemistry. Double labeling experiments reveal that the enzyme is expressed
      by astrocytes enwrapping the densely packed neurons and also the myelinated fiber
      bundles of the stria medullaris. NTPDase2 immunoreactivity is absent from the
      lateral habenula. The analysis of mice expressing enhanced green fluorescent
      protein under the promoter of glial fibrillary acidic protein revealed that the
      medial habenula harbors a highly polar type of astrocytes with very long laminar
      cellular processes, untypical for grey matter astrocytes. Its morphology strongly
      differs from that of the stellate astrocytes in the adjacent lateral habenula.
      Our results suggest that the mouse medial habenula contains a specific
      perineuronal nonstellate subtype of astrocyte that expresses the ectonucleotidase
      NTPDase2 and is in a strategic position to modulate purinergic transmission in
      this subnucleus.

PMID- 22865705
TI  - Nano-structured phosphorus composite as high-capacity anode materials for lithium
      batteries.
AB  - More than LiP service: The adsorption of red phosphorus into porous carbon
      provides a composite anode material for lithium-ion batteries. The amorphous nano
      phosphorus, in the carbon matrix, shows highly reversible lithium storage with
      high coulombic efficiencies and stable cycling capacity of 750 mAh per gram
      composite.

PMID- 22865706
TI  - Absolute risk regression for competing risks: interpretation, link functions, and
      prediction.
AB  - In survival analysis with competing risks, the transformation model allows
      different functions between the outcome and explanatory variables. However, the
      model's prediction accuracy and the interpretation of parameters may be sensitive
      to the choice of link function. We review the practical implications of different
      link functions for regression of the absolute risk (or cumulative incidence) of
      an event. Specifically, we consider models in which the regression coefficients
      beta have the following interpretation: The probability of dying from cause D
      during the next t years changes with a factor exp(beta) for a one unit change of
      the corresponding predictor variable, given fixed values for the other predictor
      variables. The models have a direct interpretation for the predictive ability of
      the risk factors. We propose some tools to justify the models in comparison with
      traditional approaches that combine a series of cause-specific Cox regression
      models or use the Fine-Gray model. We illustrate the methods with the use of bone
      marrow transplant data.

PMID- 22865707
TI  - Relative resistance or susceptibility of maple (Acer) species, hybrids and
      cultivars to six arthropod pests of production nurseries.
AB  - BACKGROUND: Maples (Acer spp.) in production nurseries are vulnerable to numerous
      arthropod pests that can stunt or even kill the young trees. Seventeen cultivars
      representing various Acer species and hybrids were evaluated for extent of
      infestation or injury by shoot and trunk borers (Proteoteras aesculana,
      Chrysobothris femorata), potato leafhopper (Empoasca fabae), Japanese beetle
      (Popillia japonica), maple spider mite (Oligonychus aceris) and calico scale
      (Eulecanium cerasorum). Evaluations were done in replicated field plots in
      central and western Kentucky. RESULTS: All of the maples were susceptible, to
      varying degrees, to one or more key pest(s). Red maples (A. rubrum) were
      relatively vulnerable to potato leafhopper injury and borers but nearly free of
      Japanese beetle feeding and spider mites. Sugar maples sustained conspicuous
      Japanese beetle damage but had very low mite populations, whereas the opposite
      was true for Freeman maples (A. * freemanii). A. campestre was heavily infested
      by calico scale. Within each species or hybrid there were cultivar differences in
      degree of infestation or damage by particular pests. CONCLUSION: The results
      should help growers to focus pest management efforts on those plantings at
      greatest risk from particular pests, and to choose cultivars requiring fewer
      insecticide inputs to produce a quality tree.

PMID- 22865708
TI  - Hierarchical structures of carbon nanotubes and arrays of chromium-capped silicon
      nanopillars: formation and electrical properties.
AB  - The formation of stochastically oriented carbon-nanotube networks on top of an
      array of free-standing chromium-capped silicon nanopillars is reported. The
      combination of nanosphere lithography and chemical vapor deposition enables the
      construction of nanostructures that exhibit a hierarchical sequence of structural
      sizes. Metallic chromium serves as an etching mask for Si-pillar formation and as
      a nucleation site for the formation of carbon nanotubes through the chemical
      vapor deposition of ethene, ethanol, and methane, respectively, thereby bridging
      individual pillars from top to top. Iron and cobalt were applied onto the
      chromium caps as catalysts for CNT growth and the influence of different carbon
      sources and different gas-flow rates were investigated. The carbon nanotubes were
      structurally characterized and their DC electrical properties were studied by in
      situ local- and ex situ macroscopic measurements, both of which reveal their
      semiconductor properties. This process demonstrates how carbon nanotubes can be
      integrated into Si-based semiconductors and, thus, this process may be used to
      form high-surface-area sensors or new porous catalyst supports with enhanced gas
      permeation properties.

PMID- 22865709
TI  - Species-specific and transgenerational responses to increasing salinity in
      sympatric freshwater gastropods.
AB  - Freshwater salinization is a global concern partly attributable to anthropogenic
      salt contamination. The authors examined the effects of increased salinity (as
      NaCl, 250-4,000 uS/cm, specific conductance) on two sympatric freshwater
      gastropods (Helisoma trivolvis and Physa pomillia). Life stage sensitivities were
      determined by exposing naive eggs or naive juveniles (through adulthood and
      reproduction). Additionally, progeny eggs from the juvenile-adult exposures were
      maintained at their respective parental salinities to examine transgenerational
      effects. Naive H. trivolvis eggs experienced delayed development at specific
      conductance > 250 uS/cm; reduced survivorship and reproduction were also seen in
      juvenile H. trivolvis at 4,000 uS/cm. Survival and growth of P. pomilia were not
      affected by increased salinity following egg or juvenile exposures.
      Interestingly, the progeny of H. trivolvis exposed to higher salinity may have
      gained tolerance to increased salinity whereas P. pomilia progeny may have
      experienced negative transgenerational effects. The present study demonstrates
      that freshwater snail species vary in their tolerance to salinization and also
      highlights the importance of multigenerational studies, as stressor impacts may
      not be readily apparent from shorter term exposures.

PMID- 22865710
TI  - Fast access to residual dipolar couplings by single-scan 2D NMR in oriented
      media.
AB  - Residual dipolar couplings (RDCs) have revolutionized the structure determination
      of biomolecular and organic compounds. So far, their measurement has been rather
      time-consuming, but one might imagine that RDCs can one day also be useful in the
      investigation of compounds with limited stability or short lifetimes. For such
      applications, it is indispensable to shorten the experiment time. In this
      communication, we show the first measurement of RDCs from single-scan two
      dimensional NMR. An ultrafast HSQC NMR pulse sequence is presented, which
      includes several of the recent improvements brought to ultrafast NMR in terms of
      sensitivity, resolution, and spectral width. Ultrafast spectra are obtained in as
      little time as 60 s on an organic compound at natural abundance, namely (+)
      isopinocampheol. When extracting the RDCs from these ultrafast data, a good
      agreement with those extracted from conventional spectra (obtained in a much
      longer time) is observed. These results point out the efficiency of the ultrafast
      approach, particularly when considering the total experiment duration.

PMID- 22865711
TI  - Using eye movements as an index of implicit face recognition in autism spectrum
      disorder.
AB  - Individuals with an autism spectrum disorder (ASD) typically show impairment on
      face recognition tasks. Performance has usually been assessed using overt,
      explicit recognition tasks. Here, a complementary method involving eye tracking
      was used to examine implicit face recognition in participants with ASD and in an
      intelligence quotient-matched non-ASD control group. Differences in eye movement
      indices between target and foil faces were used as an indicator of implicit face
      recognition. Explicit face recognition was assessed using old-new discrimination
      and reaction time measures. Stimuli were faces of studied (target) or unfamiliar
      (foil) persons. Target images at test were either identical to the images
      presented at study or altered by changing the lighting, pose, or by masking with
      visual noise. Participants with ASD performed worse than controls on the explicit
      recognition task. Eye movement-based measures, however, indicated that implicit
      recognition may not be affected to the same degree as explicit recognition.
      Autism Res 2012, 5: 363-379. (c) 2012 International Society for Autism Research,
      Wiley Periodicals, Inc.

PMID- 22865712
TI  - Screening conditions for rationally engineered electrodeposition of
      nanostructures (SCREEN): electrodeposition and applications of polypyrrole
      nanofibers using microfluidic gradients.
AB  - A rapid screening method for optimizing electrochemical deposition conditions of
      polypyrrole (PPy) nanostructures is reported. An electrochemical cell is
      integrated within a low-cost microfluidic system, in which electrochemical
      deposition is carried out across a linear concentration gradient of a reaction
      parameter. The protocol, refered to as the screening of conditions for rationally
      engineered electrodeposition of nanostructures (SCREEN), allows rapid screening
      of conditions for the production of specific morphologies by characterizing the
      electrodeposited samples produced within a chemical gradient. To demonstrate the
      utility of the SCREEN method, applications in tunable optical coatings and
      superhydrophobic surfaces are presented. 

PMID- 22865713
TI  - Cervical muscle area measurements in whiplash patients: Acute, 3, and 6 months of
      follow-up.
AB  - PURPOSE: To investigate the role of the cervical spine muscles in whiplash
      injury. We hypothesized that (i) cervical muscle hypotrophy would be evident
      after a 6-month follow-up and, (ii) cervical muscle hypotrophy would correlate
      with symptom persistence probably related to pain or inactivity. MATERIALS AND
      METHODS: Ninety symptomatic patients (48 females) were recruited from our
      emergency department and examined within 48 h, and at 3, and 6 months after a
      motor vehicle accident. MRI cross-sectional muscle area (CSA) measurements were
      performed bilaterally of the cervical extensor and sternocleidomastoid muscles
      using transverse STIR (Short Tau inversion Recovery) sequences at the C2 (deep
      and total dorsal cervical extensor muscles), C4 (sternocleidomastoid muscles) and
      C5 (deep and total dorsal cervical extensor muscles) levels. Two blinded raters
      independently performed the measurements at each time point. First, CSA changes
      over time were analyzed and, second, CSAs were correlated with clinical outcomes
      (EuroQuol, Whiplash Disability Score, neck pain intensity [VAS], cervical spine
      mobility). RESULTS: There was a high agreement of CSA measurements between the
      two raters. Women consistently had smaller CSAs than men. There were no
      significant changes of CSAs over time at any of the three levels. There were no
      consistent significant correlations of CSA values with the clinical scores at all
      time points except with the body mass index. CONCLUSION: Our results do not
      support a major role of cervical muscle volume in the genesis of symptoms after
      whiplash injury.

PMID- 22865714
TI  - Isolated interrupted aortic arch in 42-year-old adult--case report.
AB  - Interrupted aortic arch (IAA) is a rare congenital anomaly characterized by a
      complete luminal and anatomical interruption between the ascending and descending
      thoracic aorta. It is usually detected in the perinatal period or during infancy,
      but a very few cases have been reported in adults. Here, we present the case of a
      42-year-old man who visited our hospital for arterial hypertension and in whom
      IAA was diagnosed with echocardiography and confirmed by computed tomography
      angiography.

PMID- 22865715
TI  - An investigation of the transdiagnostic model of eating disorders in the context
      of muscle dysmorphia.
AB  - AIM: Muscle dysmorphia is a psychiatric disorder that has been conceptually
      linked to eating disorders, although its precise nosology remains unclear. To
      further investigate this notion, the present study examined the applicability of
      the transdiagnostic model of eating disorders to muscle dysmorphia. METHOD: One
      hundred and nineteen male undergraduate students completed self-report measures
      of multidimensional perfectionism, mood intolerance, self-esteem, interpersonal
      problems, and muscle dysmorphia symptomatology. RESULTS: Self-oriented
      perfectionism, socially prescribed perfectionism, mood intolerance, and low self
      esteem significantly predicted muscle dysmorphia symptomatology, whereas other
      oriented perfectionism and interpersonal problems did not demonstrate significant
      predictive value when accounting for the other transdiagnostic constructs.
      DISCUSSION: The transdiagnostic model of eating disorders may potentially be
      applied to enhance our understanding of the maintenance of muscle dysmorphic
      features in addition to eating disorder symptomatology.

PMID- 22865716
TI  - Comparative evaluation of three calcium phosphate synthetic block bone graft
      materials for bone regeneration in rabbit calvaria.
AB  - Various synthetic materials were developed to be used for implant dentistry and
      periodontal treatments. Among the various synthetic bone substitutes, calcium
      phosphate ceramics have been extensively investigated because their mineral
      chemistry resembles that of human bone. We evaluated the regeneration of three
      calcium phosphate synthetic block bone grafts in rabbit calvarial noncritical
      size defects. Four 8-mm-diameter defects were created in each rabbit (N = 10).
      Three defects, hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and
      biphasic calcium phosphate (BCP), were randomly filled with one of three
      fabricated synthetic block bone graft materials. The fourth defect was filled
      with blood clots. Specimens were harvested at 4 and 8 weeks postsurgery.
      Histological and histometrical findings indicated that all three calcium
      phosphate block bone graft materials were able to maintain space significantly
      better than the control group at both 4 and 8 weeks. In the BCP group, the amount
      of newly formed bone was increased more than for the other groups. Additionally,
      beta-TCP showed a large resorption of graft materials after 4 weeks postsurgery,
      while there were only small resorption for HA and BCP.

PMID- 22865717
TI  - Synthetic studies on chartelline C: stereoselective construction of the core
      skeleton.
AB  - What a core-ker! The title synthesis was achieved using a route featuring an
      intramolecular Mitsunobu reaction of a nosyl amide, stereoselective construction
      of the beta-lactam, and formation of an enamide moiety by selenoxide elimination.
      The stereochemistry of the alkylation for the formation of the beta-lactam was
      controlled by a secondary hydroxy group on the ten-membered ring. SEM=2
      (trimethylsilyl)ethoxymethyl; TBS=tert-butyldimethylsilyl.

PMID- 22865718
TI  - Adverse health effects of Asian dust particles and heavy metals in Japan.
AB  - Asian dust events are now considered an environmental problem rather than a
      natural seasonal phenomenon. In this study, we evaluated the associations between
      daily adverse health effects and Asian dust events in Yonago, Japan. Participants
      included 54 healthy volunteers, who were distributed survey sheets on nasal,
      ocular, respiratory, and skin effects in February 2009. Moreover, we collected
      meteorological and air pollutant (nitric oxide, sulfur dioxide, suspended
      particulate matter) data and determined pollen and metallic element
      concentrations in total suspended particulates. Both soil-derived metals (Fe, Ca,
      Al) and contaminating metals (Pb, Cr, Mn, Ni, Zn) were significantly increased on
      Asian dust days. Multiple regression analyses showed that the score of the skin
      effect was significantly associated with the levels of suspended particulate
      matter and Ni. The results show that increased air pollutants on Asian dust days
      may have skin effects. 

PMID- 22865719
TI  - Achutha Menon Centre Diabetes Risk Score: a type 2 diabetes screening tool for
      primary health care providers in rural India.
AB  - The authors aimed to develop a diabetes risk score for primary care providers in
      rural India. They used the baseline data of 451 participants (15-64 years) of a
      cohort study in a rural area of Kerala, India. The new risk score with age,
      family history of diabetes, and waist circumference identified 40.8% for
      confirmatory testing, had a sensitivity of 81.0%, specificity of 68.4%, positive
      predictive value of 37.0%, and negative predictive value of 94.0% for an optimal
      cutoff >=4 with an area under the receiver operating characteristic curve of
      0.812 (95% confidence interval = 0.765-0.860). The new risk score with 3 simple,
      easy-to-measure, less time-consuming, and less expensive variables could be
      suitable for use in primary care settings of rural India. 

PMID- 22865720
TI  - Adult tobacco cessation in Cambodia: II. Determinants of intent to quit.
AB  - Identifying determinants of intent to quit may aid the design of antitobacco
      programs and promote effective tobacco control policies. In a nationwide survey
      in Cambodia, two thirds of tobacco smokers and 45% of female smokeless tobacco
      users planned to stop in the future. Multivariate determinants of intent in 2279
      male smokers were age <37 years, age at initiation >= 18 years, Cham versus Khmer
      ethnicity (odds ratio [OR] = 6.93; 95% confidence interval[CI] = 1.38-34.89),
      longer education, and professional occupation. In 1188 female smokeless tobacco
      users, age <25 years, age at initiation >= 18 years, and tuberculosis (OR = 3.26;
      95% CI = 1.61-6.61) were associated with intent. In female smokers (n = 321), age
      18 to 25 years at initiation was associated with intent. In male smokers and
      female smokeless tobacco users, perceived physical advantages of tobacco were
      inversely associated with intent. These findings underscore the importance of
      policies and interventions to delay initiation and promote cessation in young
      people and counteract perceived physical benefits.

PMID- 22865721
TI  - The association of physical fitness with body mass index and waist circumference
      in Filipino preadolescents.
AB  - AIM: The objective of this study is are to examine the association of
      preadolescent obesity using body mass index (BMI) and waist circumference (WC)
      with health-related physical fitness components. METHODS: Grades 4 to 6 students
      in 2 private schools in Manila were included in this study. Height, weight, WC,
      and BMI were obtained. Physical fitness field tests were sit-and-reach test, 1
      minute sit-ups, standing broad jump, 40-m sprint, and 20-m shuttle run. RESULTS:
      Obese subjects had poorer scores in the field tests except in the sit-and-reach
      test. BMI and WC were significantly negatively associated with all the physical
      fitness parameters, except for the 40-m sprint where positive correlation was
      observed, and in the sit-and-reach test where no correlation was seen.
      CONCLUSION: In the management of preadolescent overweight and obesity, exercise
      programs should therefore be designed toward enhancing these fitness parameters,
      while not sacrificing enjoyment and creativity.

PMID- 22865722
TI  - Factors affecting life expectancy: evidence from 1980-2009 data in Singapore,
      Malaysia, and Thailand.
AB  - The authors aim to examine the impact of demographic changes, socioeconomic
      inequality, and the availability of health care resources on life expectancy in
      Singapore, Malaysia, and Thailand. This is a cross-country study collecting
      annual data from 3 Southeast Asian countries from 1980 to 2008. Life expectancy
      is the dependent variable with demographics, socioeconomic status, and health
      care resources as the 3 main determinants. A structural equation model is used,
      and results show that the availability of more health care resources and higher
      levels of socioeconomic advantages are more likely to increase life expectancy.
      In contrast, demographic changes are more likely to increase life expectancy by
      way of health care resources. The authors suggest that more effort should be
      taken to expand and improve the coverage of health care programs to alleviate
      regional differences in health care use and improve the overall health status of
      people in these 3 Southeast Asian countries. 

PMID- 22865723
TI  - The influence of the internalization of emotional regulation on mental health
      among the Taiwanese people: the moderating effect of cultural fit.
AB  - This study used a 2-stage questionnaire survey to explore whether self-regulation
      by withholding negative emotions (SRWNE) affects mental health and examines
      further whether cultural fit can moderate the relationship between SRWNE and
      mental health. The 2-stage studies used data collected from 405 (time 1) and 313
      (time 2) full-time staff employed by private and public enterprises in Taiwan.
      The author tested hypotheses through the use of hierarchical multiple regression.
      The results showed that controlled SRWNE through external regulation and
      introjected regulation is significantly associated positively with somatic
      symptoms, anxiety and insomnia, social dysfunction, and severe depression,
      whereas autonomous SRWNE through identified regulation is significantly
      associated negatively with anxiety and insomnia, and social dysfunction. In
      addition, this study also found that cultural fit may moderate the relationship
      between SRWNE or introjected regulation and identified regulation and the mental
      health indicators. 

PMID- 22865724
TI  - Synthesis of perylene dyes with multiple triphenylamine substituents.
AB  - Perylene monoimide (PMI) was brominated to give tetra- and tribrominated
      molecules, which underwent a Suzuki coupling reaction with 4
      (diphenylamino)phenylboronic acid to give PMI derivatives. The photophysical and
      electrochemical properties of the synthesized compounds were investigated, and
      theoretical calculations were performed. Single crystals of tetrasubstituted PMI
      were grown and studied in detail. The structure-property relationships were
      examined to reveal the effect of the position and number of substituents on the
      perylene core unit. All molecules showed a broad absorption up to 750 nm.
      Corresponding anhydrides of PMIs were used for fabrication of dye-sensitized
      solar cells. The molecule with four triphenylamine units on perylene
      monoanhydride showed the highest power conversion efficiency.

PMID- 22865726
TI  - Accumulation of polychlorinated biphenyls from contaminated sediment by Atlantic
      cod (Gadus morhua): direct accumulation from resuspended sediment and dietary
      accumulation via the polychaete Nereis virens.
AB  - Bioaccumulation of sediment-associated polychlorinated biphenyls (PCBs) was
      examined in Atlantic cod (Gadus morhua) through direct diffusion from the
      sediment (via the water phase) and through the food chain (dietary exposure). To
      facilitate direct accumulation from the sediment, it was continuously
      resuspended. To study the dietary bioaccumulation of PCBs, cod were fed benthic
      polychaetes (Nereis virens) previously exposed to test sediments, which were
      naturally polluted sediments from the inner Oslofjord (Norway). Both exposure
      experiments had a duration of 129 d. Furthermore, the role of sediments as a
      source of PCBs accumulated in Oslofjord cod was elucidated, using results from
      environmental monitoring as a reference. Generally, the results suggest that the
      contaminated sediments of the inner Oslofjord are an important source of legacy
      PCBs for accumulation in resident cod, although additional contributions may also
      be important. Crude estimates of assimilation efficiency of ingested PCBs
      (through diet) were found to be 30 to 50%; the highest was for the lower
      chlorinated congeners (PCB-28 and -52). Challenges for applying trophic
      magnification factors for determining biomagnification in laboratory experiments,
      in terms of preventive environmental safety, are indicated. The results provide
      useful information for parameterization of models describing the behavior of
      hydrophobic persistent contaminants in the foodweb of the Oslofjord and
      elsewhere.

PMID- 22865727
TI  - Effects of managed care mechanisms on access to healthcare: results from a
      qualitative study in Colombia.
AB  - BACKGROUND: Managed competition has underpinned most health sector reforms aimed
      at improving access and efficiency, in Latin America and other countries. The aim
      of the paper is to analyse barriers to healthcare that emerge from the
      introduction of managed care mechanisms in Colombia. METHODS: Qualitative,
      exploratory, and descriptive-interpretative research was carried out on the basis
      of case studies of four healthcare networks, comprised of insurers and their
      providers. Individual semi-structured interviews were conducted with a
      theoretical sample of informants (managers, professionals, and users), between 24
      and 61 per network. The final sample size was reached by saturation of
      information. An inductive thematic content analysis was conducted. The study
      areas were two municipalities of Colombia, in which most of the population live
      in poverty. RESULTS: A number of managed care mechanisms that act as barriers to
      access were identified by all informants, regardless of area and type of
      insurance regime. These mechanisms act directly on the patient (authorizations,
      fragmented insurance) or on the providers (purchasing mechanisms or limits to
      medical practice). The predominant mechanism appears to be related to the type of
      agreement established between insurers and providers. The reason for these
      barriers, according to informants, is insurers' search for profitability. As a
      consequence, there is delay in or no access to adequate treatment. This is
      particularly evident in secondary care. CONCLUSION: A variety of managed care
      strategies that effectively hinder access to healthcare have been introduced by
      insurers, casting doubt on the usefulness of their application in low-income
      countries and profit-making contexts.

PMID- 22865725
TI  - HIV-1 alters neural and glial progenitor cell dynamics in the central nervous
      system: coordinated response to opiates during maturation.
AB  - HIV-associated neurocognitive disorders (HANDs) are common sequelae of human
      immunodeficiency virus (HIV) infection, even when viral titers are well
      controlled by antiretroviral therapy. Evidence in patients and animal models
      suggests that neurologic deficits are increased during chronic opiate exposure.
      We have hypothesized that central nervous system (CNS) progenitor cells in both
      adult and developing CNS are affected by HIV infection and that opiates
      exacerbate these effects. To examine this question, neural progenitors were
      exposed to HIV-1 Tat(1-86) in the developing brain of inducible transgenic mice
      and in vitro. We examined whether Tat affected the proliferation or balance of
      progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was
      further tested by exposing human-derived progenitors to supernatant from HIV-1
      infected monocytes. Studies concentrated on striatum, a region preferentially
      targeted by HIV and opiates. Results were similar among experimental paradigms.
      Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2(+))
      progenitors and oligodendroglial (Olig2(+)) progenitors. Coexposure to morphine
      exacerbated the effects of Tat or HIV-1(SF162) supernatant, but partially
      reversed HIV-1(IIIB) supernatant effects. Populations of Sox2(+) and Olig2(+)
      cells were also reduced by Tat exposure, although progenitor survival was
      unaffected. In rare instances, p24 immunolabeling was detected in viable human
      progenitors by confocal imaging. The vulnerability of progenitors is likely to
      distort the dynamic balance among neuron/glial populations as the brain matures,
      perhaps contributing to reports that neurologic disease is especially prevalent
      in pediatric HIV patients. Pediatric disease is atypical in developed regions but
      remains a serious concern in resource-limited areas where infection occurs
      commonly at birth and through breast feeding.

PMID- 22865728
TI  - Olfactory outcomes following endoscopic pituitary surgery with or without septal
      flap reconstruction: a randomized controlled trial.
AB  - BACKGROUND: Postoperative hyposmia and anosmia is an often overlooked
      complication of endoscopic pituitary surgery. Septal flaps have been utilized as
      a strategy for repairing and preventing postoperative cerebrospinal fluid (CSF)
      leaks. The olfactory impact of raising this flap for sellar reconstruction and
      CSF repair needs qualitative assessment. This study aims to ascertain the effect
      of the Hadad-Bassagasteguy (HB) flap on olfaction in endoscopic pituitary
      surgery. METHODS: In this randomized controlled trial, patients undergoing
      pituitary surgery underwent computerized randomization. Those in Group 1 all had
      HB flaps raised and placed for sellar floor defects. Those in Group 2 underwent
      reconstruction with synthetic or nonautologous materials. The University of
      Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively
      and 6 months postoperatively. Results were analyzed using nonparametric tests.
      RESULTS: Twenty subjects were enrolled, 10 in each group. Eight subjects in Group
      1 vs 3 in Group 2 had intraoperative CSF leak. All were repaired intraoperatively
      and none required additional intervention. Preoperatively, UPSIT scores were not
      significantly different between groups (p = 0.62). Preoperative vs postoperative
      comparisons were significant for a decrease in scores in both groups
      postoperatively (Group 1, p < 0.001; Group 2, p < 0.001). Those undergoing HB
      flap reconstruction had significantly worse scores postoperatively (p = 0.001).
      CONCLUSION: Endoscopic pituitary surgery results in decreased olfaction with or
      without deploying a septal flap. However, use of the HB flap for reconstruction
      can worsen hyposmia at least 6 months after surgery. Olfaction should be
      considered when use of the HB flap is planned.

PMID- 22865729
TI  - Design and analysis of non-pharmacological treatment trials with multiple
      therapists per patient.
AB  - In trials of physical and talking therapies, nesting of patients within
      therapists has statistical implications analogous to those of cluster randomised
      trials. Nevertheless, the clustering effect may be more complex, as it interacts
      with treatment. For some therapies, individual patients may receive care from
      multiple therapists of the same type, so that patients are no longer strictly
      nested within therapists, creating a 'multiple-membership' relationship between
      patients and therapists. This paper considers methods of analysis and sample size
      estimation for trials with multiple-membership clustering effects. It is
      motivated by a trial of a psychotherapy for the treatment of adolescent
      depression with cognitive behavioural therapy. We tested methods and issues in a
      Monte Carlo simulation study, simulating trials with multiple membership. Results
      demonstrate satisfactory performance in terms of convergence and give estimates
      of the intra-cluster correlation coefficient and empirical test size similar to a
      simple hierarchical design. We derive formulae for sample size and power for
      multiple-membership trial designs. We then compare estimates of power from this
      formula with empirical power derived from the simulation study. Finally, we show
      that we can easily extend formulae for sample size and power to allow
      consideration of power and sample size for certain types of more complex
      interventions. These include situations where therapists of different types
      deliver separate components of the intervention, creating a cross-classified
      relationship, or where several therapists deliver a group-administered treatment,
      creating further levels.

PMID- 22865730
TI  - Mesenchymal stromal cells: are they all good for the liver?

PMID- 22865731
TI  - Coating of single DNA molecules by genetically engineered protein diblock
      copolymers.
AB  - Coating DNA is an effective way to modulate its physical properties and
      interactions. Current chemosynthetic polymers form DNA aggregates with random
      size and shape. In this study, monodisperse protein diblock copolymers are
      produced at high yield in recombinant yeast. They carry a large hydrophilic
      colloidal block (~400 amino acids) linked to a short binding block (~12 basic
      amino acids). It is demonstrated that these protein polymers complex single DNA
      molecules as highly stable nanorods, reminiscent of cylindrical viruses. It is
      proposed that inter- and intramolecular bridging of DNA molecules are prevented
      completely by the small size of the binding block attached to the large colloidal
      stability block. These protein diblocks serve as a scaffold that can be tuned for
      application in DNA-based nanotechnology. 

PMID- 22865732
TI  - Multiple pathways of duplication formation with and without recombination (RecA)
      in Salmonella enterica.
AB  - Duplications are often attributed to "unequal recombination" between separated,
      directly repeated sequence elements (>100 bp), events that leave a recombinant
      element at the duplication junction. However, in the bacterial chromosome,
      duplications form at high rates (10(-3)-10(-5)/cell/division) even without
      recombination (RecA). Here we describe 1800 spontaneous lac duplications trapped
      nonselectively on the low-copy F'(128) plasmid, where lac is flanked by direct
      repeats of the transposable element IS3 (1258 bp) and by numerous
      quasipalindromic REP elements (30 bp). Duplications form at a high rate (10(
      4)/cell/division) that is reduced only about 11-fold in the absence of RecA. With
      and without RecA, most duplications arise by recombination between IS3 elements
      (97%). Formation of these duplications is stimulated by IS3 transposase (Tnp) and
      plasmid transfer functions (TraI). Three duplication pathways are proposed.
      First, plasmid dimers form at a high rate stimulated by RecA and are then
      modified by deletions between IS3 elements (resolution) that leave a monomeric
      plasmid with an IS3-flanked lac duplication. Second, without RecA, duplications
      occur by single-strand annealing of DNA ends generated in different sister
      chromosomes after transposase nicks DNA near participating IS3 elements. The
      absence of RecA may stimulate annealing by allowing chromosome breaks to persist.
      Third, a minority of lac duplications (3%) have short (0-36 bp) junction
      sequences (SJ), some of which are located within REP elements. These duplication
      types form without RecA, Tnp, or Tra by a pathway in which the palindromic
      junctions of a tandem inversion duplication (TID) may stimulate deletions that
      leave the final duplication.

PMID- 22865733
TI  - Maximizing the reliability of genomic selection by optimizing the calibration set
      of reference individuals: comparison of methods in two diverse groups of maize
      inbreds (Zea mays L.).
AB  - Genomic selection refers to the use of genotypic information for predicting
      breeding values of selection candidates. A prediction formula is calibrated with
      the genotypes and phenotypes of reference individuals constituting the
      calibration set. The size and the composition of this set are essential
      parameters affecting the prediction reliabilities. The objective of this study
      was to maximize reliabilities by optimizing the calibration set. Different
      criteria based on the diversity or on the prediction error variance (PEV) derived
      from the realized additive relationship matrix-best linear unbiased predictions
      model (RA-BLUP) were used to select the reference individuals. For the latter, we
      considered the mean of the PEV of the contrasts between each selection candidate
      and the mean of the population (PEVmean) and the mean of the expected
      reliabilities of the same contrasts (CDmean). These criteria were tested with
      phenotypic data collected on two diversity panels of maize (Zea mays L.)
      genotyped with a 50k SNPs array. In the two panels, samples chosen based on
      CDmean gave higher reliabilities than random samples for various calibration set
      sizes. CDmean also appeared superior to PEVmean, which can be explained by the
      fact that it takes into account the reduction of variance due to the relatedness
      between individuals. Selected samples were close to optimality for a wide range
      of trait heritabilities, which suggests that the strategy presented here can
      efficiently sample subsets in panels of inbred lines. A script to optimize
      reference samples based on CDmean is available on request.

PMID- 22865734
TI  - Demographic inference using spectral methods on SNP data, with an analysis of the
      human out-of-Africa expansion.
AB  - We present an implementation of a recently introduced method for estimating the
      allele-frequency spectrum under the diffusion approximation. For single
      nucleotide polymorphism (SNP) frequency data from multiple populations, the
      method computes numerical solutions to the allele-frequency spectrum (AFS) under
      a complex model that includes population splitting events, migration, population
      expansion, and admixture. The solution to the diffusion partial differential
      equation (PDE) that mimics the evolutionary process is found by means of
      truncated polynomial expansions. In the absence of gene flow, our computation of
      frequency spectra yields exact results. The results are compared to those that
      use a finite-difference method and to forward diffusion simulations. In general,
      all the methods yield comparable results, although the polynomial-based approach
      is the most accurate in the weak-migration limit. Also, the economical use of
      memory attained by the polynomial expansions makes the study of models with four
      populations possible for the first time. The method was applied to a four
      population model of the human expansion out of Africa and the peopling of the
      Americas, using the Environmental Genome Project (EGP) SNP database. Although our
      confidence intervals largely overlapped previous analyses of these data, some
      were significantly different. In particular, estimates of migration among
      African, European, and Asian populations were considerably lower than those in a
      previous study and the estimated time of migration out of Africa was earlier. The
      estimated time of founding of a human population outside of Africa was 52,000
      years (95% confidence interval: 36,000-80,800 years).

PMID- 22865735
TI  - An indel polymorphism in the hybrid incompatibility gene lethal hybrid rescue of
      Drosophila is functionally relevant.
AB  - Hybrid incompatibility (HI) genes are frequently observed to be rapidly evolving
      under selection. This observation has led to the attractive conjecture that
      selection-derived protein-sequence divergence is culpable for incompatibilities
      in hybrids. The Drosophila simulans HI gene Lethal hybrid rescue (Lhr) is an
      intriguing case, because despite having experienced rapid sequence evolution, its
      HI properties are a shared function inherited from the ancestral state. Using an
      unusual D. simulans Lhr hybrid rescue allele, Lhr(2), we here identify a
      conserved stretch of 10 amino acids in the C terminus of LHR that is critical for
      causing hybrid incompatibility. Altering these 10 amino acids weakens or
      abolishes the ability of Lhr to suppress the hybrid rescue alleles Lhr(1) or
      Hmr(1), respectively. Besides single-amino-acid substitutions, Lhr orthologs
      differ by a 16-aa indel polymorphism, with the ancestral deletion state fixed in
      D. melanogaster and the derived insertion state at very high frequency in D.
      simulans. Lhr(2) is a rare D. simulans allele that has the ancestral deletion
      state of the 16-aa polymorphism. Through a series of transgenic constructs we
      demonstrate that the ancestral deletion state contributes to the rescue activity
      of Lhr(2). This indel is thus a polymorphism that can affect the HI function of
      Lhr.

PMID- 22865736
TI  - The chromosomal passenger complex is required for meiotic acentrosomal spindle
      assembly and chromosome biorientation.
AB  - During meiosis in the females of many species, spindle assembly occurs in the
      absence of the microtubule-organizing centers called centrosomes. In the absence
      of centrosomes, the nature of the chromosome-based signal that recruits
      microtubules to promote spindle assembly as well as how spindle bipolarity is
      established and the chromosomes orient correctly toward the poles is not known.
      To address these questions, we focused on the chromosomal passenger complex
      (CPC). We have found that the CPC localizes in a ring around the meiotic
      chromosomes that is aligned with the axis of the spindle at all stages. Using new
      methods that dramatically increase the effectiveness of RNA interference in the
      germline, we show that the CPC interacts with Drosophila oocyte chromosomes and
      is required for the assembly of spindle microtubules. Furthermore, chromosome
      biorientation and the localization of the central spindle kinesin-6 protein
      Subito, which is required for spindle bipolarity, depend on the CPC components
      Aurora B and Incenp. Based on these data we propose that the ring of CPC around
      the chromosomes regulates multiple aspects of meiotic cell division including
      spindle assembly, the establishment of bipolarity, the recruitment of important
      spindle organization factors, and the biorientation of homologous chromosomes.

PMID- 22865737
TI  - Microtubule-depolymerizing kinesin KLP10A restricts the length of the
      acentrosomal meiotic spindle in Drosophila females.
AB  - During cell division, a bipolar array of microtubules forms the spindle through
      which the forces required for chromosome segregation are transmitted.
      Interestingly, the spindle as a whole is stable enough to support these forces
      even though it is composed of dynamic microtubules, which are constantly
      undergoing periods of growth and shrinkage. Indeed, the regulation of microtubule
      dynamics is essential to the integrity and function of the spindle. We show here
      that a member of an important class of microtubule-depolymerizing kinesins,
      KLP10A, is required for the proper organization of the acentrosomal meiotic
      spindle in Drosophila melanogaster oocytes. In the absence of KLP10A, microtubule
      length is not controlled, resulting in extraordinarily long and disorganized
      spindles. In addition, the interactions between chromosomes and spindle
      microtubules are disturbed and can result in the loss of contact. These results
      indicate that the regulation of microtubule dynamics through KLP10A plays a
      critical role in restricting the length and maintaining bipolarity of the
      acentrosomal meiotic spindle and in promoting the contacts that the chromosomes
      make with microtubules required for meiosis I segregation.

PMID- 22865738
TI  - The relation of codon bias to tissue-specific gene expression in Arabidopsis
      thaliana.
AB  - The codon composition of coding sequences plays an important role in the
      regulation of gene expression. Herein, we report systematic differences in the
      usage of synonymous codons among Arabidopsis thaliana genes that are expressed
      specifically in distinct tissues. Although we observed that both regionally and
      transcriptionally associated mutational biases were associated significantly with
      codon bias, they could not explain the observed differences fully. Similarly,
      given that transcript abundances did not account for the differences in codon
      usage, it is unlikely that selection for translational efficiency can account
      exclusively for the observed codon bias. Thus, we considered the possible
      evolution of codon bias as an adaptive response to the different abundances of
      tRNAs in different tissues. Our analysis demonstrated that in some cases, codon
      usage in genes that were expressed in a broad range of tissues was influenced
      primarily by the tissue in which the gene was expressed maximally. On the basis
      of this finding we propose that genes that are expressed in certain tissues might
      show a tissue-specific compositional signature in relation to codon usage. These
      findings might have implications for the design of transgenes in relation to
      optimizing their expression.

PMID- 22865739
TI  - Independent FLC mutations as causes of flowering-time variation in Arabidopsis
      thaliana and Capsella rubella.
AB  - Capsella rubella is an inbreeding annual forb closely related to Arabidopsis
      thaliana, a model species widely used for studying natural variation in adaptive
      traits such as flowering time. Although mutations in dozens of genes can affect
      flowering of A. thaliana in the laboratory, only a handful of such genes vary in
      natural populations. Chief among these are FRIGIDA (FRI) and FLOWERING LOCUS C
      (FLC). Common and rare FRI mutations along with rare FLC mutations explain a
      large fraction of flowering-time variation in A. thaliana. Here we document
      flowering time under different conditions in 20 C. rubella accessions from across
      the species' range. Similar to A. thaliana, vernalization, long photoperiods and
      elevated ambient temperature generally promote flowering. In this collection of
      C. rubella accessions, we did not find any obvious loss-of-function FRI alleles.
      Using mapping-by-sequencing with two strains that have contrasting flowering
      behaviors, we identified a splice-site mutation in FLC as the likely cause of
      early flowering in accession 1408. However, other similarly early C. rubella
      accessions did not share this mutation. We conclude that the genetic basis of
      flowering-time variation in C. rubella is complex, despite this very young
      species having undergone an extreme genetic bottleneck when it split from C.
      grandiflora a few tens of thousands of years ago.

PMID- 22865742
TI  - A racemic polar cobalt phosphonate with weak ferromagnetism.
AB  - Comfortably nemp: A novel polar compound [Co(2)(nemp)(2)(H(2)O)(2) ]
      incorporating racemic [1-(1-naphthyl)ethylamino]methylphosphonate (nemp(2-)) as a
      ligand is reported (see packing structure). This compound shows nonlinear optical
      properties at room temperature and weak ferromagnetism below 2 K.

PMID- 22865741
TI  - Improving membrane binding as a design strategy for amphipathic peptide hormones:
      2-helix variants of PYY3-36.
AB  - It has been hypothesized that amphipathic peptides might bind to membranes prior
      to activating their cognate receptors, but this has proven difficult to test. The
      peptide hormone PYY3-36 is believed to perform its appetite-suppressing actions
      through binding to hypothalamic Y2 receptors. It has been proposed that PYY3-36
      via its amphipathic alpha-helix binds to the plasma membrane prior to receptor
      docking. Here, our aim was to study the implication of this hypothesis using new
      analogs of PYY3-36. We first studied membrane binding of PYY3-36. Next, we
      designed a series of PYY3-36 analogs to increase membrane-binding affinity by
      substituting the N-terminal segment with a de novo designed alpha-helical,
      amphipathic sequence. These 2-helix variants of PYY3-36 were assembled by solid
      phase peptide synthesis. Pharmacological studies demonstrated that even though
      the native peptide sequence was radically changed, highly active Y2 receptor
      agonists were generated. A potent analog, with a Kd of 4 nM for membranes, was
      structurally characterized by NMR in the membrane-bound state, which clearly
      showed that it formed the expected 2-helix. The topology of the peptide-micelle
      association was studied by paramagnetic relaxation enhancement using a spin
      label, which confirmed that the hydrophobic residues bound to the membrane. Our
      studies further support the hypothesis that PYY3-36 associates with the membrane
      and indicate that this can be used in the design of novel molecules with high
      receptor binding potency. These observations are likely to be generally important
      for peptide hormones and biopharmaceutical drugs derived from them. This new 2
      helix variant of PYY3-36 will be useful as a tool compound for studying peptide
      membrane interactions.

PMID- 22865740
TI  - In vitro response of osteoarthritic chondrocytes and fibroblast-like synoviocytes
      to a 500-730 kDa hyaluronan amide derivative.
AB  - The aim of this study was to compare the effects of native hyaluronan (HA) with
      that of its hexadecylamide derivative (HYADD) on proliferation of fibroblast-like
      synoviocytes (FLS) and chondrocytes. The production of inflammatory and anti
      inflammatory cytokines was also analyzed in FLS cultures. The proliferation of
      osteoarthritis (OA) chondrocytes was enhanced when cells were treated with 0.5
      1.5 mg mL(-1) of HA or HYADD(r)4-G. This effect was completely suppressed by the
      anti-CD44 antibody. At 0.5 to 1 mg mL(-1) , HA and HYADD(r)4-G did not influence
      the proliferation of normal or pathological FLS; however, at the higher
      concentration (1.5 mg mL(-1) ), HYADD(r)4-G did significantly inhibit cell
      proliferation. As to effects on inflammation, a significant increase in the
      expression of the IL-10 gene was observed when FLS were pretreated with tumor
      necrosis factor alpha and then cultured in the presence of 0.5 mg mL(-1) HYADD(r)
      4-G or HA. The effects of HA derivatives on FLS proliferation and production of
      anti-inflammatory cytokines indicate that they may be of therapeutic benefit in
      OA. The longer residence time in the joint cavity, the increased viscoelasticity,
      and the anti-inflammatory potential of HYADD(r)4-G make it a better candidate
      than native HA for OA therapy.

PMID- 22865743
TI  - A yolk-shell nanoreactor with a basic core and an acidic shell for cascade
      reactions.
AB  - Smart yolk-shell nanoparticles (hollow nanoparticles with a movable core) with an
      acidic shell and a basic core were fabricated through an organosilane-assisted
      selective etching method and acted as efficient nanoreactors for catalyzing a
      deacetalization-Henry cascade reaction with high activity and high selectivity.
      This strategy is very promising for the design of multifunctional nanoreactors
      for cascade reactions.

PMID- 22865744
TI  - Direct soil contact values for ecological receptors exposed to weathered
      petroleum hydrocarbon (PHC) fraction 2.
AB  - Ecological tier 1 Canada-wide standards (CWS) for petroleum hydrocarbon (PHC)
      fraction 2 (F2; >nC10-C16) in soil were derived using ecotoxicological assessment
      endpoints (effective concentrations [ECs]/lethal concentrations [LCs]/inhibitory
      concentrations, 25% [IC25s]) with freshly spiked (fresh) fine- and coarse-grained
      soils. These soil standards might be needlessly conservative when applied to
      field samples with weathered hydrocarbons. The purpose of the present study was
      to assess the degradation and toxicity of weathered PHC F2 in a fine-grained soil
      and to derive direct soil contact values for ecological receptors. Fine-grained
      reference soils were spiked with distilled F2 and weathered for 183 d. Toxicity
      tests using plants and invertebrates were conducted with the weathered F2-spiked
      soils. Endpoint EC/IC25s were calculated and used to derive soil standards for
      weathered F2 in fine-grained soil protective of ecological receptors exposed via
      direct soil contact. The values derived for weathered F2 were less restrictive
      than current ecological tier 1 CWS for F2 in soil.

PMID- 22865745
TI  - Diffusion of new technology, health services and information after a crisis: a
      focus group study of the Sichuan "5.12" Earthquake.
AB  - INTRODUCTION: The Sichuan "5.12" Earthquake in 2008 occurred in a relatively
      underdeveloped area in China. The rainy weather, the mountainous environment and
      the local languages all posed major challenges to the dissemination of
      information and services after the disaster. By adopting a communication
      perspective, this study applies the diffusion of innovations theory to
      investigate how healthcare professionals diffused health technologies, health
      information and services during the rescue and relief operation. METHOD: The
      authors conducted three focus group sessions with the health professionals who
      had attended to the rescue and relief work of the Sichuan "5.12" Earthquake in
      2008. A range of questions regarding the diffusion of innovations were asked
      during these sessions. RESULTS: The health professionals used their cell phones
      to communicate with other healthcare providers, disseminated knowledge of health
      risks and injuries to affected residents with pamphlets and posters and attended
      daily meetings at the local government offices. They reported on the shortage of
      maritime satellite cell phones and large-size tents for medical use, and the
      absence of fully equipped ambulances. Volunteers, local health professionals and
      local officials provided health information and services in different ways.
      However, the diffusion of health information and services was less likely to
      reach those living next to transportation centers, in remote areas and in
      disaster areas neglected by the media. DISCUSSION: New communication devices such
      as cell phones and the mobile Internet enabled medical professionals to
      coordinate the rescue and relief work after this major natural disaster, at a
      time when the country's emergency response system still had plenty of room for
      improvement. In future, the mobile Internet should be used as a means of
      collecting bottom-up disaster reports so that the media will not neglect any
      disaster areas as they did during the Sichuan Earthquake. Rescue relief work
      would have been substantially easier if medical teams had been equipped with
      advanced appliances such as maritime satellite cell phones. "Disaster medicine"
      should be treated as a separate discipline in medical schools and receive more
      investment. Moreover, a stronger public health emergency response system is
      needed for more efficient dispatch and coordination.

PMID- 22865746
TI  - A retrospective review of UroVysion fish interpretations over 8.6 years: a major
      shift in the patient test population.
AB  - UroVysion FISH detects chromosomal aberrations associated with urothelial
      carcinoma. In our laboratory, UroVysion FISH was initially evaluated manually
      with a change to image-aided interpretation using the BioView Duet imaging
      system. This retrospective study examined diagnostic findings over an 8.6 year
      period, with 1,869 manual interpretations over 4.8 years and 3,936 image-aided
      interpretations over 3.8 years. Although the initial goal was to evaluate
      possible impacts of the imaging system on diagnostic interpretations, the most
      important finding was that the demographics of the test population changed
      significantly. Female specimens increased incrementally from an average of 29%
      compared to 43% of the samples during periods of manual interpretation versus
      image-aided interpretation, respectively. The shift may reflect a gradual
      increase in the percentage of low-risk hematuria patients being evaluated for
      initial diagnosis of bladder cancer, rather than bladder cancer recurrence.
      Interpretation rates, evaluated separately for males and females, changed
      significantly over the test period. Male interpretation results were negative
      (75.1 vs. 67%), positive (18.6 vs. 14.6%), unsatisfactory (5.0 vs. 16.9%), and
      equivocal (1.4 vs. 1.5%) during periods of manual versus image-aided
      interpretation, respectively (Fisher Exact Test P-value = <0.0001). For females,
      results were negative (86.1 vs. 79.3%), positive (9.2 vs. 11.1%), unsatisfactory
      (2.8 vs. 8.9%), and equivocal (1.8 vs. 0.7%) over the same periods (Fisher Exact
      Test P-value = <0.0001). Logistic regression analysis identified the change in
      test population as the variable with the greatest impact on observed
      interpretation rate changes.

PMID- 22865747
TI  - Mental health 15 years after the killings in Rwanda: imprisoned perpetrators of
      the genocide against the Tutsi versus a community sample of survivors.
AB  - Objectives of this study were to compare rates of mental health disorders in
      Rwandan genocide perpetrators with those of genocide survivors and to investigate
      potential predictors of symptoms of posttraumatic stress disorder (PTSD) and
      depression for both groups. We expected high rates of mental disorders in both
      study groups and hypothesized that symptom severity would be predicted by female
      gender, older age, lower level of education, higher level of trauma exposure,
      lower level of agreement to reconciliation, and the participation in killing.
      Structured clinical interviews were carried out with 269 imprisoned perpetrators
      (66% men) and 114 survivors (64% women). Significantly more survivors than
      perpetrators met symptom criteria for PTSD (46% vs. 14%) and suffered from
      anxiety symptoms (59% vs. 36%). A substantial proportion of both groups suffered
      from clinically significant depression (46% vs. 41%). PTSD severity in
      perpetrators was associated with trauma exposure, high levels of agreement to
      reconciliation, and no participation in killing; the severity of depression was
      associated with trauma exposure and no participation in killing. In the survivor
      sample, the severity of PTSD and depression were both correlated with female
      gender, trauma exposure, and low levels of agreement to reconciliation. Results
      suggest that both groups exhibit considerable psychiatric morbidity.

PMID- 22865748
TI  - Extending methods for investigating the relationship between treatment effect and
      baseline risk from pairwise meta-analysis to network meta-analysis.
AB  - Baseline risk is a proxy for unmeasured but important patient-level
      characteristics, which may be modifiers of treatment effect, and is a potential
      source of heterogeneity in meta-analysis. Models adjusting for baseline risk have
      been developed for pairwise meta-analysis using the observed event rate in the
      placebo arm and taking into account the measurement error in the covariate to
      ensure that an unbiased estimate of the relationship is obtained. Our objective
      is to extend these methods to network meta-analysis where it is of interest to
      adjust for baseline imbalances in the non-intervention group event rate to reduce
      both heterogeneity and possibly inconsistency. This objective is complicated in
      network meta-analysis by this covariate being sometimes missing, because of the
      fact that not all studies in a network may have a non-active intervention arm. A
      random-effects meta-regression model allowing for inclusion of multi-arm trials
      and trials without a 'non-intervention' arm is developed. Analyses are conducted
      within a Bayesian framework using the WinBUGS software. The method is illustrated
      using two examples: (i) interventions to promote functional smoke alarm ownership
      by households with children and (ii) analgesics to reduce post-operative morphine
      consumption following a major surgery. The results showed no evidence of baseline
      effect in the smoke alarm example, but the analgesics example shows that the
      adjustment can greatly reduce heterogeneity and improve overall model fit.

PMID- 22865749
TI  - Mind as a risk factor for cancer-some comments.

PMID- 22865750
TI  - Trekking new ground: overcoming medical and social impediments for extended
      criteria liver transplant recipients.
AB  - KEY POINTS: 1. There is an increasing recognition that previously marginal
      candidates for liver transplantation can receive therapies that allow transplant
      to take place. 2. Coronary artery disease is an increasing co-morbidity in liver
      transplant candidates. 3. Physio-social issues require written guidelines and
      patient advocates. 4. Methadone maintenance therapy per se is not a contra
      indication to liver transplantation.

PMID- 22865751
TI  - A novel chiral mesoporous binaphthyl-silicas: preparation, characterization, and
      application in HPLC.
AB  - Mesoporous organosilicas with both R-(+)-1,1'-binaphthyl-2,2'-diamine and ethane
      moieties bridging in the framework were synthesized. This mesoporous material was
      prepared via the one-step co-condensation of N,N'-bis-[(triethoxysilyl)propyl]
      (R)-bis-(ureido)-binaphthyl (Si-DABN) with 1,2-bis(triethoxysilyl)ethane (BTSE)
      using octadecyltrimethylammonium chloride (C(18) TMACl) as a structural directing
      agent with the aid of a co-solvent (ethanol) in basic medium. The morphology of
      these bifunctionalized mesoporous organosilicas is sensitive to the Si-DABN mole
      fraction and the base concentration. And the mesostructure becomes less ordered
      as the mole fraction of Si-DABN in the initial mixture increases from 10 to 40%.
      Elemental analysis and Fourier transform infrared (FT-IR) spectrometer indicate
      that the binaphthyl diamine was successfully introduced to the mesoporous
      organosilicas. Acidic conditions are more suitable than basic ones for the
      hydrolysis and condensation of (R)-2,2'-dicyanomethoxy-6,6'-di[(2
      triethoxysilyl)ethenyl]-1,1'-binaphthyl, a chiral silane precursors with a short
      silane side chain on the binaphthyl group. A column packed with these
      bifunctionalized mesoporous organosilica spheres exhibits greater selectivity for
      R/S-1,1'-bi-2,2'-naphthol than one packed with commercial SiO(2)  grafted with
      N,N'-bis-[(triethoxysilyl)propyl]-(R)-bis-(ureido)-binaphthyl. Binaphthol and
      bromosubstituted binaphthol were fully resolved, but two ether derivatives were
      only partially enantioseparated and the other three ester derivatives were no
      fully resolved on the column via co-condensation method.

PMID- 22865752
TI  - HPLC enantioseparation of alkaloid malacitanine using fluorimetric/polarimetric
      detection.
AB  - This work reports two methods developed for the separation and determination of
      the enantiomers of the new alkaloid malacitanine (MLC) and the determination of
      the enantiomeric purity in mixtures. First, the isomers were separated using a
      Chirex 3020 (250 mm * 4.6 mm, 5 MUm) chiral column with a mobile phase of
      cyclohexane-1,2-dichloroethane-ethanol-trifluoroacetic acid (64:30:6:0.6,
      v/v/v/v) at a flow rate of 1 mL/min and fluorimetric detection. Obtained
      retention times were 12.4 and 15.9 min (+ and -) with a resolution Rs of 1.13.
      Relative standard deviations (RSDs) were 2.5 and 2.4% at the 0.5-MUg level (four
      determinations). Second, a nonenantioselective procedure for the determination of
      enantiomeric purity of MLC using a Lichrospher (r) Si-60 (250 mm * 5 mm, 5 MUm)
      normal phase with a mobile phase of 100% ethanol at a flow rate of 0.9 mL/min
      coupled to two detectors in series, fluorimetric and polarimetric. RSD of 3.3%
      was obtained. Calculated enantiomeric purity by chiral chromatography gave 48.6%
      (-)-MLC in the near racemic product. Using polarimetric signal of the
      nonseparated enantiomers and comparing the slopes of the calibration curves
      (enantiomers) from the racemic product gave 47.8% (-)-MLC content. A study of
      accuracy of (-)-MLC gave recoveries from 98.3 to 100.7%.

PMID- 22865753
TI  - Hydrodynamic chromatography separations in micro- and nanopillar arrays produced
      using deep-UV lithography.
AB  - We report on a series of hydrodynamic chromatography separations conducted in
      micropillar array columns with an interpillar distance spacing of, respectively,
      1.00, 0.70, and 0.47 MUm. The columns have been produced using state-of-the-art
      deep-UV lithography and deep reactive ion etching techniques. Despite the fact
      that the efficiency was smaller than theoretically possible (due to fabrication
      limitations and significant injection and detection band broadening), it was
      nevertheless possible to separate mixtures of fluorescein isothiocyanate (used as
      the t(0) -marker) and 20- and 40-nm polystyrene beads. With the smallest
      interpillar distance, a resolution of R(s)  = 0.5 between the 20- and 40-nm
      particles could be obtained in 90s over a column length of 4 cm. The selectivity
      obtained in the pillar array columns was found to be very similar to that
      observed in packed-bed columns. By detecting the fluorescent signals in a 90-MUm
      deep detection groove at the end of the column, the signal-to-noise ratio could
      be enhanced up to 150 times.

PMID- 22865754
TI  - Simultaneous determination of eight bufadienolides in cinobufacini injection by
      HPLC coupled with triple quadrupole mass spectrometry.
AB  - A rapid and validated method was established for the simultaneous determination
      of eight active and toxic bufadienolides in cinobufacini injection using high
      performance liquid chromatography coupled with triple quadrupole mass
      spectrometry. These eight compounds were separated within 3 min on a C(18) 
      analytical column with gradient elution. Eleven batches of cinobufacini injection
      were analyzed with good linear regression relationship (r, 0.9979-0.9999),
      precisions (RSD, 1.92-4.79%), repeatability (RSD, 3.12-4.96%), stability (RSD,
      2.84-4.45%), and recovery (93.96-104.89%). By using the established method, the
      present study offered highly sensitive, specific, and speedy determination of
      eight bufadienolides, which promoted the quality control investigation of
      cinobufacini injection greatly.

PMID- 22865755
TI  - Alternative method for gas chromatography-mass spectrometry analysis of short
      chain fatty acids in faecal samples.
AB  - Short-chain fatty acids are the major end products of bacterial metabolism in the
      large bowel. They derive mostly from the bacterial breakdown of carbohydrates and
      are known to have positive health benefits. Due to the biological relevance of
      these compounds it is important to develop efficient, cheap, fast, and sensitive
      analytical methods that enable the identification and quantification of the short
      chain fatty acids in a large number of biological samples. In this study, a gas
      chromatography-mass spectrometry method was developed and validated for the
      analysis of short-chain fatty acids in faecal samples. These volatile compounds
      were extracted with ethyl acetate and 4-methyl valeric acid was used as an
      internal standard. No further cleanup, concentration, and derivatization steps
      were needed and the extract was directly injected onto the column. Recoveries
      ranged between 65 and 105%, and no matrix effects were observed. The proposed
      method has wide linear ranges, good inter- and intraday variability values (below
      2.6 and 5.6%, respectively) and limits of detection between 0.49 MUM (0.29 MUg/g)
      and 4.31 MUM (3.8 MUg/g). The applicability of this analytical method was
      successfully tested in faecal samples from rats and humans.

PMID- 22865756
TI  - Evaluation of the solid-phase extraction (SPE) cartridge method in combination
      with thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) for the
      analysis of different VOCs in liquid matrices in varying pH conditions.
AB  - In this study, the solid-phase extraction (SPE) method combined with thermal
      desorption-gas chromatography-mass spectrometry (TD-GC-MS) method is evaluated
      for the analysis of liquid-phase volatile organic compounds (LVOCs). Calibration
      experiments were performed on a number of polar and nonpolar LVOCs (including
      aromatic compounds, ester, ketones, and alcohol) as a function of solution pH. If
      the relative sensitivity of the SPE-TD-GC-MS method is compared between different
      VOCs across a wide range of pH (1, 4, 7, 10, and 13), optimum sensitivities for
      most VOCs are derived at the neutral pH. However, there were some exceptions to
      the general trend with the maximum sensitivity occurring either at a moderately
      basic pH (methyl isobutyl ketone and butyl acetate) or extremely acidic
      conditions (isobutyl alcohol). It was also noticed that the relative ordering of
      sensitivity was changed, as the pH conditions of the solution vary. The use of
      internal standard (IS: chlorobenzene) resulted in a notable improvement in both
      relative sensitivity and reproducibility for most compounds.

PMID- 22865757
TI  - Fabrication of acrylate monolith using photopolymerization: effect of light
      intensity on electrochromatographic performance.
AB  - A hexyl acrylate monolith was prepared via photopolymerization into a cyclic
      olefin copolymer micro-device for reversed-phase electrochromatography purposes.
      This work deals with the influence of the irradiation conditions (irradiation
      time and light intensity) used during synthesis on the electrochromatographic
      performances of the monolithic column obtained. Up to day, the monolith structure
      was often controlled by means of irradiation time at constant light intensity,
      but the effect of light intensity (irradiance) on the monolith structure was
      scarcely considered. This study shows a strong effect of light intensity on
      electrochromatographic efficiency. Using an optimal light intensity of 4.7
      mW/cm(2)  and an irradiation time of a few minutes allows obtaining heights
      equivalent to a theoretical plate reaching down to 5 MUm for the reversed-phase
      separation of six polycyclic aromatic hydrocarbons.

PMID- 22865758
TI  - Comparison of different imidazolium supported ionic liquid polymeric phases with
      strong anion-exchange character for the extraction of acidic pharmaceuticals from
      complex environmental samples.
AB  - Two imidazolium supported ionic liquid phases (SILPs) containing different
      anions, trifluoromethanesulphonate [CF(3)SO(3)(-)], and tetrafluoroborate [BF(4)(
      )], were synthesized and evaluated as solid-phase extraction sorbents for
      extracting acidic pharmaceuticals from aqueous samples under strong anion
      exchange conditions, which include an effective cleanup of the sample. The best
      SILP material [MI(+)][CF(3)SO(3)(-) ] was selected and successfully applied to
      the determination of acidic pharmaceuticals in different types of water samples
      (river water and effluent wastewater). The results were then compared to the
      previously synthesized SILP material based on [MI(+)][CF(3)COO(-)] and the
      commercially available Oasis MAX sorbent.

PMID- 22865759
TI  - Preparation of cyano-functionalized multiwalled carbon nanotubes as solid-phase
      extraction sorbent for preconcentration of phenolic compounds in environmental
      water.
AB  - In the present work, we showed a novel method to synthesize cyano-functionalized
      multiwalled carbon nanotubes (MWCNTs-CN) and utilize it as a solid-phase
      extraction sorbent for preconcentration of phenolic compounds in environmental
      water samples. MWCNTs-CN was synthesized through surface functionalization of
      multiwalled carbon nanotubes (MWCNTs). The functional groups on the surface of
      modified MWCNTs were characterized by Fourier transform infrared spectroscopy,
      thermogravimetric analysis and scanning electron microscopy. The analytical
      procedure was based on a conventional solid-phase extraction step for which 100
      mg of MWCNTs-CN were packed in a 3 mL polypropylene cartridge. Analytes were thus
      isolated and preconcentrated from the pretreated samples and subsequently
      detected on high-performance liquid chromatography-ultraviolet detection. The
      results showed the proposed method exhibited good sensitivity and precision for
      the extraction and elution of analytes. The limit of detections (S/N = 3) of the
      method were 0.45, 0.09, 0.08, and 3.00 ng mL(-1)  for p-chlorophenol, 1-naphthol,
      2-naphthol, and 2,4-dichlorophenol, respectively. The mean relative recoveries (n
      = 3) were between 80.28 and 103.13%, and the repeatability (RSD <= 5.10%) and
      reproducibility (RSD <= 7.68%) were accepted. This developed method was applied
      to determine phenolic compounds in environmental water samples. There is a
      positive result only for 2-naphthol with concentration of 0.38 ng mL(-1)  in
      seawater sample.

PMID- 22865760
TI  - Preparative purification of five bioactive components from Agrimonia pilosa Ledeb
      by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) coupled with ultraviolet (UV)
      detection or evaporative light-scattering detection was successfully applied for
      preparative separation of five bioactive compounds from Agrimonia pilosa Ledeb.
      In preliminary process, D101 macroporous resin was used to separate the crude
      extract of the plant and four fractions (20, 40, 50, and 60% aqueous ethanol
      elutions) were produced. Then, these fractions were directly subjected to HSCCC
      purification. Five chemicals including taxifolin-3-glucoside (6.4 mg), quercetin
      3-rhamnoside (13.0 mg), tiliroside (14.7 mg), agrimonolide (21.4 mg), and
      tormentic acid (29.8 mg) with the purities of 94.24, 95.37, 97.42, 95.29, and
      96.34% were separated from each 200 mg prepared fraction. The purities were
      analyzed by high-performance liquid chromatography, and the chemical structures
      of the products were identified by UV detection, mass spectrometry, nuclear
      magnetic resonance, and the standards. This paper used a simple method to
      separate five bioactive compounds from A. pilosa Ledeb, and it could provide a
      new idea for the purification of bioactive compounds from other medicinal plants.

PMID- 22865761
TI  - Analysis of liposomes using asymmetrical flow field-flow fractionation:
      separation conditions and drug/lipid recovery.
AB  - Liposomes composed of dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylglycerol were analyzed by asymmetrical flow field-flow
      fractionation coupled with multi-angle laser light scattering. In addition to
      evaluation of fractionation conditions (flow conditions, sample mass, carrier
      liquid), radiolabeled drug-loaded liposomes were used to determine the liposome
      recovery and a potential loss of incorporated drug during fractionation. Neither
      sample concentration nor the cross-flow gradient distinctly affected the size
      results but at very low sample concentration (injected mass 5 MUg) the fraction
      of larger vesicles was underestimated. Imbalance in the osmolality between the
      inner and outer aqueous phase resulted in liposome swelling after dilution in
      hypoosmotic carrier liquids. In contrast, liposome shrinking under hyperosmotic
      conditions was barely visible. The liposomes themselves eluted completely (lipid
      recoveries were close to 100%) but there was a loss of incorporated drugs during
      separation with a strong dependence on the octanol-water partition coefficient of
      the drug. Whereas corticosterone (partition coefficient ~2) was washed out more
      or less completely (recovery about 2%), loss of temoporfin (partition coefficient
      ~9) was only minor (recovery about 80%). All fractionations were well repeatable
      under the experimental conditions applied in the present study.

PMID- 22865764
TI  - Synthesis and properties of cyclic gomesin and analogues.
AB  - Gomesin (Gm) was the first antimicrobial peptide (AMP) isolated from the
      hemocytes of a spider, the Brazilian mygalomorph Acanthoscurria gomesiana. We
      have been studying the properties of this interesting AMP, which also displays
      anticancer, antimalarial, anticryptococcal and anti-Leishmania activities. In the
      present study, the total syntheses of backbone-cyclized analogues of Gm (two
      disulfide bonds), [Cys(Acm)(2,15)]-Gm (one disulfide bond) and
      [Thr(2,6,11,15),(D)-Pro(9)]-Gm (no disulfide bonds) were accomplished, and the
      impact of cyclization on their properties was examined. The consequence of
      simultaneous deletion of pGlu(1) and Arg(16) -Glu-Arg(18) -NH(2) on Gm
      antimicrobial activity and structure was also analyzed. The results obtained
      showed that the synthetic route that includes peptide backbone cyclization on
      resin was advantageous and that a combination of 20% DMSO/NMP, EDC/HOBt, 60 
      degrees C and conventional heating appears to be particularly suitable for
      backbone cyclization of bioactive peptides. The biological properties of the Gm
      analogues clearly revealed that the N-terminal amino acid pGlu(1) and the
      amidated C-terminal tripeptide Arg(16) -Glu-Arg(18) -NH(2) play a major role in
      the interaction of Gm with the target membranes. Moreover, backbone cyclization
      practically did not affect the stability of the peptides in human serum; it also
      did not affect or enhanced hemolytic activity, but induced selectivity and, in
      some cases, discrete enhancements of antimicrobial activity and salt tolerance.
      Because of its high therapeutic index, easy synthesis and lower cost, the
      [Thr(2,6,11,15),(D)-Pro(9)]-Gm analogue remains the best active Gm-derived AMP
      developed so far; nevertheless, its elevated instability in human serum may limit
      its therapeutic potential.

PMID- 22865765
TI  - A new highly versatile handle for chemistry on a solid support: the pipecolic
      linker.
AB  - The versatility of the pipecolic linker (Pip-linker) is illustrated by the
      synthesis of modified amino acids, C-terminal-modified pseudopeptides, and cyclic
      peptides, through side-chain anchoring of a lysine residue (see figure).
      Introduction of the first residue was easily accomplished and the Pip-linker
      revealed to be robust enough to support various chemical modifications.

PMID- 22865766
TI  - Mechanical properties of human bone surrounding plateau root form implants
      retrieved after 0.3-24 years of function.
AB  - Bone remodeling, along with tissue biomechanics, is critical for the clinical
      success of endosseous implants. This study evaluated the long-term evolution of
      the elastic modulus (GPa) and hardness (GPa) of cortical bone around human
      retrieved plateau root form implants. Thirty implant-in-bone specimens showing no
      clinical failure were retrieved from patients at different in-vivo times (0.3 to
      ~24 years) due to retreatment needs. After dehydration, specimens were embedded
      in methacrylate-based resin, sectioned along the bucco-lingual long axis and
      fixed to acrylic plates and nondecalcified processed to slides with ~50 MUm in
      thickness. Nanoindentation testing was carried out under wet conditions on bone
      areas within the first three plateaus. Indentations (n = 120 per implant total)
      were performed with a maximum load of 300 MUN (loading rate: 60 MUN/s) followed
      by a holding and unloading time of 10 s and 2 s, respectively. Elastic modulus
      (E, GPa) and hardness (H, GPa) were computed. Both E and H values presented
      increased values as time in vivo elapsed (E: r = 0.84; H: r = 0.78).
      Significantly higher values for E and H were found after 5 years in vivo (p <
      0.001). Maxillary or mandibulary arches or positioning did not affect mechanical
      properties, nor did implant surface treatment on the long-term bone biomechanical
      response (E: p >= 0.09; H: p >= 0.3). This work suggests that human cortical bone
      around plateau root form implants presents an increase in elastic modulus and
      hardness during the first 5 years following implantation and presents stable
      mechanical properties thereafter.

PMID- 22865768
TI  - Lys53 of ribosomal protein L36AL and the CCA end of a tRNA at the P/E hybrid site
      are in close proximity on the human ribosome.
AB  - Previously we have shown that the CCA end of a P-tRNA can be crosslinked with the
      RPL36AL protein of the large subunit of mammalian ribosomes; it belongs to the
      L44e protein family present in all eukaryotic and archaeal ribosomes. Here we
      confirm and extend this finding and demonstrate that: 1) this crosslink is
      specific for a tRNA at the P/E hybrid site, as a tRNA in all other tRNA positions
      of pre-translocational ribosomes could not be crosslinked with a ribosomal
      protein, 2) the crosslink was formed most efficiently with C74 and C75 of P/E
      tRNA, but could also connect the ultimate A of this tRNA with Lys53 of protein
      RPL36AL, 3) this protein contains seven monomethylated residues (three lysyl and
      three arginyl residues, as well as glutaminyl residue 51), 4) Q51 is part of a
      conserved GGQ motif in the L44e proteins in eukaryotic 80S ribosomes that is
      identical to the universally conserved motif of release factors implicated in
      promoting peptidyl-tRNA hydrolysis, and 5) the large number of modifications, in
      which some of the residues were methylated to about 50 %, might indicate that
      protein RPL36AL is a preferential target for regulation.

PMID- 22865770
TI  - Metastatic small cell osteosarcoma to the liver: a diagnostic pitfall for fine
      needle aspiration cytology.
AB  - We report the fine-needle aspiration cytology of a case of metastatic small cell
      osteosarcoma to the liver with rosette formation, originating from distal femur,
      in a 36-year-old female. The aspirate of the liver metastases revealed a
      relatively monomorphic population of mitotically active small blue round cells
      arranged in clusters with prominent rosette formation simulating a neuroendocrine
      carcinoma or other rosette-forming small round cell tumors such as Ewing sarcoma.
      No extracellular mineralized matrix material was present. Comparison of the liver
      aspirate with the biopsy from the distal femoral lesion was crucial in reaching
      the correct diagnosis of metastatic small cell osteosarcoma with rosette
      formation. This is a potential diagnostic pitfall, particularly if interpreted
      without the knowledge of a suspected primary bone tumor.

PMID- 22865772
TI  - Incidence of jaw lesions and activity and gene expression of hepatic P4501A
      enzymes in mink (Mustela vison) exposed to dietary 2,3,7,8-tetrachlorodibenzo-p
      dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran.
AB  - This study assessed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8 tetrachlorodibenzofuran
      (TCDF) on the incidence of jaw lesions and on hepatic cytochrome P4501A (CYP1A)
      endpoints in mink (Mustela vison). Adult female mink were assigned randomly to
      one of 13 dietary treatments (control and four increasing doses of TCDD, PeCDF,
      or TCDF) and provided spiked feed for approximately 150 d (60 d prior to breeding
      through weaning of offspring at 42 d post-parturition). Offspring were maintained
      on their respective diets for an additional 150 d. Activity of hepatic CYP1A
      enzymes in adult and juvenile mink exposed to TCDD, PeCDF, or TCDD was generally
      greater compared with controls, but changes in other CYP1A endpoints were less
      consistent. Histopathology of the mandible and maxilla of juvenile mink suggested
      a dose-related increase in the incidence of jaw lesions. The dietary effective
      doses (ED) for jaw lesions in 50% of the population (ED50) were estimated to be
      6.6, 14, and 149 ng/kg body weight (bw)/d for TCDD, PeCDF, and TCDF,
      respectively. The relative potencies of PeCDF and TCDF compared with TCDD based
      on ED10, ED20, and ED50 values ranged from 0.5 to 1.9 and 0.04 to 0.09,
      respectively. These values are within an order of magnitude of the World Health
      Organization toxic equivalency factor (TEF(WHO)) values of 0.3 and 0.1 for PeCDF
      and TCDF, respectively.

PMID- 22865771
TI  - Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of
      mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in
      treatment-naive fracture cases compared with fracture-free controls.
AB  - After the age of 60 years, hip fracture risk strongly increases, but only a fifth
      of this increase is attributable to reduced bone mineral density (BMD, measured
      clinically). Changes in bone quality, specifically bone composition as measured
      by Fourier transform infrared spectroscopic imaging (FTIRI), also contribute to
      fracture risk. Here, FTIRI was applied to study the femoral neck and provide
      spatially derived information on its mineral and matrix properties in age-matched
      fractured and nonfractured bones. Whole femoral neck cross sections, divided into
      quadrants along the neck's axis, from 10 women with hip fracture and 10 cadaveric
      controls were studied using FTIRI and micro-computed tomography. Although 3
      dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix
      ratio was reduced in the cases of hip fracture, confirming previous reports. New
      findings were that the FTIRI microscopic variation (heterogeneity) of the mineral
      to-matrix ratio was substantially reduced in the fracture group as was the
      heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity
      of crystallinity was increased. Increased variation of crystallinity was
      statistically associated with reduced variation of the carbonate-to-phosphate
      ratio. Anatomical variation in these properties between the different femoral
      neck quadrants was reduced in the fracture group compared with controls. Although
      our treatment-naive patients had reduced rather than increased bending
      resistance, these changes in heterogeneity associated with hip fracture are in
      another way comparable to the effects of experimental bisphosphonate therapy,
      which decreases heterogeneity and other indicators of bone's toughness as a
      material.

PMID- 22865773
TI  - Charcot arthropathy of the hip simulating a neoplastic lesion.

PMID- 22865774
TI  - A conditional error function approach for subgroup selection in adaptive clinical
      trials.
AB  - Growing interest in personalised medicine and targeted therapies is leading to an
      increase in the importance of subgroup analyses. If it is planned to view
      treatment comparisons in both a predefined subgroup and the full population as co
      primary analyses, it is important that the statistical analysis controls the
      familywise type I error rate. Spiessens and Debois (Cont. Clin. Trials, 2010, 31,
      647-656) recently proposed an approach specific for this setting, which
      incorporates an assumption about the correlation based on the known sizes of the
      different groups, and showed that this is more powerful than generic multiple
      comparisons procedures such as the Bonferroni correction. If recruitment is slow
      relative to the length of time taken to observe the outcome, it may be efficient
      to conduct an interim analysis. In this paper, we propose a new method for an
      adaptive clinical trial with co-primary analyses in a predefined subgroup and the
      full population based on the conditional error function principle. The
      methodology is generic in that we assume test statistics can be taken to be
      normally distributed rather than making any specific distributional assumptions
      about individual patient data. In a simulation study, we demonstrate that the new
      method is more powerful than previously suggested analysis strategies.
      Furthermore, we show how the method can be extended to situations when the
      selection is not based on the final but on an early outcome. We use a case study
      in a targeted therapy in oncology to illustrate the use of the proposed
      methodology with non-normal outcomes.

PMID- 22865775
TI  - Bone morphogenetic proteins regulate hinge point formation during neural tube
      closure by dynamic modulation of apicobasal polarity.
AB  - BACKGROUND: A critical event in neural tube closure is the formation of median
      hinge points (MHPs) and dorsolateral hinge points (DLHPs). Together, they buckle
      the ventral midline and elevate and juxtapose the neural folds for proper neural
      tube closure. Dynamic cell behaviors occur at hinge points (HPs), but their
      molecular regulation is largely unexplored. Bone morphogenetic proteins (BMPs)
      have been implicated in a variety of neural tube closure defects, although the
      underlying mechanisms are poorly understood. METHODS: In this study, we used in
      vivo electroporations, high-resolution microscopy, and biochemical analyses to
      explore the role of BMP signaling in chick midbrain neural tube closure. RESULTS:
      We identified a cell-cycle-dependent BMP gradient in the midbrain neural plate,
      which results in low-level BMP activity at the MHP. We show that although BMP
      signaling does not have a role in midbrain cell-fate specification, its
      attenuation is necessary and sufficient for MHP formation and midbrain closure.
      BMP blockade induces MHP formation by regulating apical constriction and basal
      nuclear migration. Furthermore, BMP signaling is critically important for
      maintaining epithelial organization by biochemically interacting with apicobasal
      polarity proteins (e.g., PAR3). As a result, prolonged BMP blockade disrupts
      apical junctions, desegregating the apical (PAR3(+), ZO1(+)) and basolateral
      (LGL(+)) compartments. Direct apical LGL-GFP misexpression in turn is sufficient
      to induce ectopic HPs. CONCLUSIONS: BMPs have a critical role in maintaining
      epithelial organization, a role that is conserved across species and tissue
      types. Its cell-cycle-dependent modulation in the neural plate dynamically
      regulates apicobasal polarity and helps to bend, shape, and close the neural
      tube.

PMID- 22865776
TI  - Poly(ethylene imine)s as antimicrobial agents with selective activity.
AB  - We report the structure-activity relationship in the antimicrobial activity of
      linear and branched poly(ethylene imine)s (L- and B-PEIs) with a range of
      molecular weights (MWs) (500-12,000). Both L- and B-PEIs displayed enhanced
      activity against Staphylococcus aureus over Escherichia coli. Both B- and L-PEIs
      did not cause any significant permeabilization of E. coli cytoplasmic membrane. L
      PEIs induced depolarization of S. aureus membrane although B-PEIs did not. The
      low MW B-PEIs caused little or no hemolysis while L-PEIs are hemolytic. The low
      MW B-PEIs are less cytotoxic to human HEp-2 cells than other PEIs. However, they
      induced significant cell viability reduction after 24 h incubation. The results
      presented here highlight the interplay between polymer size and structure on
      activity.

PMID- 22865777
TI  - P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile
      allodynia/hyperalgesia following trigeminal nerve injury.
AB  - BACKGROUND: The present study directly addresses the roles of the P2X(7) receptor
      (P2X(7)R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in
      the induction of orofacial pain following chronic constriction injury (CCI) of
      the infraorbital nerve (IoN). METHODS: Rats were anesthetized, and ligatures of 4
      0 chromic gut were tied around the IoN. A438079, a P2X(7)R antagonist or
      SB203580, a phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK)
      inhibitor, was infused intrathecally into CCI-treated rats. In another group of
      rats, 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), a P2X(7) R
      agonist, was infused intrathecally with A438079, SB203580 or etanercept, a tumor
      necrosis factor (TNF)-alpha receptor-binding recombinant drug. RESULTS: CCI of
      the IoN induced tactile allodynia/hyperalgesia and up-regulation of P2X(7)R,
      membrane-bound TNF-alpha (mTNF-alpha) and soluble TNF-alpha (sTNF-alpha) in the
      trigeminal sensory nuclear complex (TNC). Tactile allodynia/hyperalgesia or up
      regulation of mTNF-alpha and sTNF-alpha in the TNC following CCI of the IoN was
      inhibited by A438079. SB203580 also attenuated tactile allodynia/hyperalgesia or
      up-regulation of mTNF-alpha, but not the up-regulation of sTNF-alpha in the TNC.
      Treatment of rats with BzATP induced tactile allodynia/hyperalgesia and up
      regulation of sTNF-alpha and p-p38 in the TNC. Tactile allodynia/hyperalgesia or
      up-regulation of sTNF-alpha following BzATP treatment was inhibited by SB203580
      and etanercept. CONCLUSIONS: Based on these findings, phosphorylation of p38 MAPK
      via P2X(7)R may induce tactile allodynia/hyperalgesia, which is most likely
      mediated by sTNF-alpha released by microglia.

PMID- 22865778
TI  - The proportion of tumor-stroma as a strong prognosticator for stage II and III
      colon cancer patients: validation in the VICTOR trial.
AB  - BACKGROUND: The intra-tumor stroma percentage in colon cancer (CC) patients has
      previously been reported by our group as a strong independent prognostic
      parameter. Patients with a high stroma percentage within the primary tumor have a
      poor prognosis. PATIENTS AND METHODS: Tissue samples from the most invasive part
      of the primary tumor of 710 patients (52% Stage II, 48% Stage III) participating
      in the VICTOR trial were analyzed for their tumor-stroma percentage. Stroma-high
      (>50%) and stroma-low (<=50%) groups were evaluated with respect to survival
      times. RESULTS: Overall and disease-free survival times (OS and DFS) were
      significantly lower in the stroma-high group (OS P<0.0001, hazard ratio
      (HR)=1.96; DFS P<0.0001, HR=2.15). The 5-year OS was 69.0% versus 83.4% and DFS
      58.6% versus 77.3% for stroma-high versus stroma-low patients. CONCLUSION: This
      study confirms the intra-tumor stroma ratio as a prognostic factor. This
      parameter could be a valuable and low cost addition to the TNM status and next to
      current high-risk parameters such as microsatellite instability status used in
      routine pathology reporting. When adding the stroma-parameter to the ASCO
      criteria, the rate of 'undertreated' patients dropped from 5.9% to 4.3%, the
      'overtreated' increased with 6.8% but the correctly classified increased with an
      additional 14%.

PMID- 22865779
TI  - Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil
      (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal
      cancer patients.
AB  - BACKGROUND: To report our prospective experience on the incidence and pattern of
      oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with
      colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin
      (XELOX). PATIENTS AND METHODS: One hundred and fifty patients scheduled to be
      treated with either FOLFOX or XELOX for CRC were prospectively monitored at
      baseline and followed-up during chemotherapy. The incidence and severity of
      symptoms secondary to OXA-IPN were recorded using three different types of
      assessment, i.e. the motor and neurosensory National Cancer Institute common
      toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total
      neuropathy score (TNSc) and electrophysiological scores. RESULTS: Patients
      treated with either FOLFOX-4 or XELOX manifested similar incidence rates and
      severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased
      incidence of chronic neurotoxicity, compared with XELOX-treated patients (n =
      64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose
      during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity
      of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those
      treated with XELOX. CONCLUSION: The incidence of acute neurotoxicity during
      FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more
      neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA
      cumulative dose.

PMID- 22865780
TI  - Enhanced expression of the PDGFR/Abl signaling pathway in aromatase inhibitor
      resistant breast cancer.
AB  - BACKGROUND: We have found that the platelet-derived growth factor receptor
      (PDGFR)/Abl signaling pathway is up-regulated as a determinant of the acquisition
      of resistance to estrogen deprivation in vitro. We aimed to determine its
      clinical relevance in aromatase inhibitor (AI)-resistant breast cancer. PATIENTS
      AND METHODS: We identified a cohort of 45 patients with estrogen receptor
      positive breast cancer who had been treated with an AI, subsequently relapsed and
      had biopsy material available from both the presentation and post-AI recurrent
      lesion. PDGFRalpha, PDGFRbeta and Abl expression was assessed in formalin-fixed
      paraffin-embedded sections. RESULTS: Tumor protein expression of PDGFRalpha (1.39
      fold, P=0.0065), PDGFRbeta (4.32-fold, P=0.006) and Abl (1.8-fold, P=0.001) was
      increased at the point of relapse. Tumor and stromal expression of PDGFRalpha as
      well as PDGFRbeta was significantly correlated in pre-treatment and relapse
      samples. High post-treatment tumor and stromal PDGFRbeta levels were associated
      with a short time to treatment failure (TTF). Expression of PDGFRalpha in
      relapsing tumor specimens was correlated with Abl expression and Ki67 levels.
      Furthermore, changes in Abl correlated significantly with changes in ER
      expression. CONCLUSIONS: These clinical data support a role for enhanced PDGF/Abl
      signaling in AI-resistant disease and provide a rationale for targeting the
      pathway in endocrine-resistant breast cancer.

PMID- 22865782
TI  - Relationship between specific adverse events and efficacy of exemestane therapy
      in early postmenopausal breast cancer patients.
AB  - BACKGROUND: Many adverse events (AEs) associated with aromatase inhibitors (AIs)
      involve symptoms related to the depletion of circulating estrogens, and may be
      related to efficacy. We assessed the relationship between specific AEs [hot
      flashes (HF) and musculoskeletal AEs (MSAE)] and survival outcomes in Dutch and
      Belgian patients treated with exemestane (EXE) in the Tamoxifen Exemestane
      Adjuvant Multinational (TEAM) trial. Additionally, the relationship between
      hormone receptor expression and AEs was assessed. METHODS: Efficacy end points
      were relapse-free survival (RFS), overall survival (OS) and breast cancer
      specific mortality (BCSM), starting at 6 months after starting EXE treatment. AEs
      reported in the first 6 months of treatment were included. Specific AEs comprised
      HF and/or MSAE. Landmark analyses and Cox proportional hazards models assessed
      survival differences up to 5 years. RESULTS: A total of 1485 EXE patients were
      included. Patients with HF had a better RFS than patients without HF
      [multivariate hazard ratio (HR) 0.393, 95% confidence interval (CI) 0.19-0.813; P
      = 0.012]. The occurrence of MSAE versus no MSAE did not relate to better RFS
      (multivariate HR 0.677, 95% CI 0.392-1.169; P = 0.162). Trends were maintained
      for OS and BCSM. Quantitative hormone receptor expression was not associated with
      specific AEs. CONCLUSIONS: Some AEs associated with estrogen depletion are
      related to better outcomes and may be valuable biomarkers in AI treatment.

PMID- 22865781
TI  - Overcoming resistance and restoring sensitivity to HER2-targeted therapies in
      breast cancer.
AB  - BACKGROUND: Approximately 15%-23% of breast cancers overexpress human epidermal
      growth factor receptor 2 (HER2), which leads to the activation of signaling
      pathways that stimulate cell proliferation and survival. HER2-targeted therapy
      has substantially improved outcomes in patients with HER2-positive breast cancer.
      However, both de novo and acquired resistance are observed. DESIGN: A literature
      search was performed to identify proposed mechanisms of resistance to HER2
      targeted therapy and identified novel targets in clinical development for
      treating HER2-resistant disease. RESULTS: Proposed HER2-resistance mechanisms
      include impediments to HER2-inhibitor binding, signaling through alternative
      pathways, upregulation of signaling pathways downstream of HER2, and failure to
      elicit an appropriate immune response. Although continuing HER2 inhibition beyond
      progression may provide an additional clinical benefit, the availability of novel
      therapies targeting different mechanisms of action could improve outcomes. The
      developmental strategy with the most available data is targeting the
      phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin
      (mTOR) pathway. The oral mTOR inhibitor everolimus has shown promising activity
      in combination with chemotherapy and trastuzumab in trastuzumab-refractory,
      advanced breast cancer. CONCLUSIONS: Non-HER2-targeted therapy is a promising
      means of overcoming resistance to HER2-targeted treatment. Ongoing clinical
      studies will provide additional information on the efficacy and safety of novel
      targeted therapies in HER2-resistant advanced breast cancer.

PMID- 22865783
TI  - Progressive increase of inflammatory biomarkers in chronic kidney disease and end
      stage renal disease.
AB  - Chronic kidney disease (CKD) has reached epidemic levels. It is a multisystem
      disease associated with elevated systemic inflammatory and hypercoagulable
      states. Most concerning are the cardiovascular risks associated with all stages
      of kidney disease. It is difficult to assess kidney disease stage progression and
      cardiovascular risk with current indicators such as estimated glomerular
      filtration rate and conventional cardiovascular risk factors. However, the use of
      biomarkers to assess the underlying pathological disease state may bridge the
      gap. This study evaluated biomarkers of inflammation including C-reactive
      protein, d-dimer, neuron-specific enolase, neutrophil gelatinase-associated
      lipocalin, tumor necrosis factor receptor I, and thrombomodulin in 3 groups of
      patients: CKD stages 2-4, end-stage renal disease (ESRD), and age-matched
      controls. The study demonstrated a statistically significant progressive
      upregulation in mean concentration of all markers when comparing controls to CKD
      and ESRD. Therefore, biomarkers may be able to evaluate the inflammatory state in
      kidney disease and potentially predict the cardiovascular risk.

PMID- 22865784
TI  - Alloyed (ZnS)x(CuInS2)(1-x) semiconductor nanorods: synthesis, bandgap tuning and
      photocatalytic properties.
AB  - Rod-like nanocrystals of the semiconductor alloy (ZnS)(x)(CuInS(2))(1-x) (ZCIS)
      have been colloidally prepared by using a one-pot non-injection-based synthetic
      strategy. The ZCIS nanorods crystallize in the hexagonal wurtzite structure and
      display preferential growth in the direction of the c axis. The bandgap of these
      quarternary alloyed nanorods can be conveniently tuned by varying the ratio of
      ZnS to CuInS(2). A non-linear relationship between the bandgap and the alloy
      composition is observed. The ZCIS nanorods are found to exhibit promising
      photocatalytic behaviour in visible-light-driven degradation of Rhodamine B.

PMID- 22865785
TI  - The A9 core sequence from NRPS adenylation domain is relevant for thioester
      formation.
AB  - The adenylation (A) domain in nonribosomal peptide synthetases catalyses a two
      step reaction in which an amino acid is activated and then transferred to the
      neighbouring thiolation (T) domain. In this study, we investigated the role of
      the conserved A9 core sequence of the A-domain of tyrocidine synthetase 1, by
      analysis of single amino acid mutations in the A9 region. Mutation of an
      absolutely conserved proline (P490G) significantly reduced the conformational
      stability of the protein, as evidenced by increased susceptibility to proteolytic
      cleavage and denaturation. All mutant A-domains were capable of amino acid
      activation, but the activity in the overall reaction was reduced. Surprisingly,
      the S491R mutant (mutation at the first residue following the A9 motif) showed
      elevated overall activity compared to the wild-type protein. Our results suggest
      that the A9 core sequence plays a role in the second reaction step, in which it
      could serve as a "clip" for the proper positioning of residues important for the
      interaction with the T-domain, and/or stabilisation of the thioester-forming
      conformation.

PMID- 22865786
TI  - Adenoid cystic carcinoma of the external auditory canal successfully diagnosed by
      fine-needle aspiration.

PMID- 22865787
TI  - Impaired bone microarchitecture at the distal radius in older men with low muscle
      mass and grip strength: the STRAMBO study.
AB  - The aim was to study the association between bone microarchitecture and muscle
      mass and strength in older men. Volumetric bone mineral density (vBMD) and bone
      microarchitecture were assessed in 810 men aged >=60 years at the distal radius
      by high-resolution peripheral computed tomography (HR-pQCT). Areal bone mineral
      density (aBMD) and appendicular muscle mass (ASM) were assessed by dual-energy X
      ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM-u.l.) was
      calculated as ASM of the upper limbs/(height)(2). Grip strength was measured by
      dynanometry. In multivariable models, men in the lowest RASM-u.l. quartile had
      lower cross-sectional area (CSA), cortical area (Ct.Ar), cortical thickness
      (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the
      highest quartile. The trends remained significant after adjustment for grip
      strength. Men in the lowest quartile of the normalized grip strength (grip
      strength/[height](2)) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and
      Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD,
      Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM-u.l. In
      the models including RASM-u.l. and normalized grip strength, CSA and Tb.Ar were
      associated with RASM-u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and
      Tb.N were associated with lower grip strength but not with RASM-u.l. Lower Ct.Ar
      was associated with lower grip strength and with lower RASM-u.l. In conclusion,
      in older men, low RASM-u.l. and low grip strength are associated with poor
      cortical and trabecular microarchitecture partly independently of each other,
      after adjustment for confounders.

PMID- 22865788
TI  - Materials research at Nanyang Technological University, Singapore.

PMID- 22865792
TI  - Adult fathead minnow, Pimephales promelas, partial life-cycle reproductive and
      gonadal histopathology study with bisphenol A.
AB  - Bisphenol A (BPA) is an intermediate used to produce epoxy resins and
      polycarbonate plastics. Although BPA degrades rapidly in the environment with
      aquatic half-lives from 0.5 to 6 d, it can be found in aquatic systems because of
      widespread use. To evaluate potential effects from chronic exposure, fathead
      minnows were exposed for 164 d to nominal concentrations of 1, 16, 64, 160, and
      640 ug/L BPA. Population-level endpoints of survival, growth, and reproduction
      were assessed with supplemental endpoints (e.g., vitellogenin, gonad histology),
      including gonad cell type assessment and quantification. No statistically
      significant changes in growth, gonad weight, gonadosomatic index, or reproduction
      variables (e.g., number of eggs and spawns, hatchability) were observed; however,
      there was a significant impact on male survival at 640 ug/L. Vitellogenin
      increased in both sexes at 64 ug/L or higher. Gonad cell type frequencies were
      significantly different from controls at 160 ug/L or higher in males with a
      slight decrease in spermatocytes compared with less mature cell types, and at 640
      ug/L in females with a slight decrease in early vitellogenic cells compared with
      less mature cells. The decrease in spermatocytes did not correspond to a decrease
      in the most mature sex cell type (spermatozoa) and did not impair male fertility,
      as hatchability was not impacted. Overall, marginal shifts in gametogenic cell
      maturation were not associated with any statistically significant effects on
      population-relevant reproductive endpoints (growth, fecundity, and hatchability)
      at any concentration tested.

PMID- 22865794
TI  - Does sepsis treatment differ between primary and overflow intensive care units?
AB  - BACKGROUND: Sepsis is a major cause of death in hospitalized patients. Early goal
      directed therapy is the standard of care. When primary intensive care units
      (ICUs) are full, sepsis patients are cared for in overflow ICUs. OBJECTIVE: To
      determine if process-of-care measures in the care of sepsis patients differed
      between primary and overflow ICUs at our institution. DESIGN: We conducted a
      retrospective study of all adult patients admitted with sepsis between July 2009
      and February 2010 to either the primary ICU or the overflow ICU. MEASUREMENTS:
      Baseline patient characteristics and multiple process-of-care measures, including
      diagnostic and therapeutic interventions. RESULTS: There were 141 patients
      admitted with sepsis to our hospital; 100 were cared for in the primary ICU and
      41 in the overflow ICU. Baseline acute physiology and chronic health evaluation
      (APACHE II) scores were similar. Patients received similar processes-of-care in
      the primary ICU and overflow ICU with the exception of deep vein thrombosis (DVT)
      and gastrointestinal (GI) prophylaxis within 24 hours of admission, which were
      better adhered to in the primary ICU (74% vs 49%, P = 0.004, and 68% vs 44%, P =
      0.012, respectively). There were no significant differences in hospital and ICU
      length of stay between the 2 units (9.68 days vs 9.73 days, P = 0.98, and 4.78
      days vs 4.92 days, P = 0.97, respectively). CONCLUSIONS: Patients with sepsis
      admitted to the primary ICU and overflow ICU at our institution were managed
      similarly. Overflowing sepsis patients to non-primary intensive care units may
      not affect guideline-concordant care delivery or length of stay.

PMID- 22865795
TI  - Increased cold and heat pain thresholds influence the thermal grill illusion in
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia show decreased sensitivity towards
      clinical and experimental painful conditions. To date, the exact underlying
      mechanisms are not completely understood. One method to examine central
      integrative processes of pain perception is the thermal grill illusion (TGI), in
      which interlacing cold and warm bars create the illusion of a painful sensation.
      METHODS: In 18 unmedicated patients with acute paranoid schizophrenia, cold and
      heat pain thresholds (CPT/HPT) as well as the perception of the TGI were examined
      and compared to 18 matched controls. In addition, symptom scales were obtained in
      order to relate pain perception to psychopathology. RESULTS: CPT and HPT were
      significantly increased in patients compared to controls. In the range of TGI
      stimuli that were perceived painful by controls, patients did not indicate
      painful sensations, instead the stimulus response curve of TGI pain perception
      was shifted towards higher stimulus intensities, i.e., greater temperature
      differentials between cold and warm bars. This increase was comparable to that
      seen in CPT and HPT. There was no association with psychopathology for any pain
      parameter. CONCLUSIONS: CPT and HPT, as well as temperature differentials for the
      perception of the TGI were increased in patients with schizophrenia as compared
      to controls. Similar to visual illusions, in which reduced contrast sensitivity
      has been shown to alter the perception of illusions, the discriminatory
      somatosensory deficit, which is reflected in higher CPT and HPT as well as the
      previously reported increased warmth perception thresholds, might account for the
      attenuation of TGI in patients.

PMID- 22865797
TI  - Contrast in electron-transfer mediation between graphene oxide and reduced
      graphene oxide.
AB  - The properties of graphene oxide (GO) and DNA-stabilised reduced graphene-oxide
      (rGO) sheets as electron-transfer mediators in partially blocked electrodes are
      evaluated employing electrochemical impedance spectroscopy. Evidences obtained
      from UV/Vis, Raman and FTIR spectroscopies, as well as atomic force microscopy,
      confirm that the reduction of exfoliated GO single sheets by hydrazine yields
      partially reduced graphene oxide featuring a high defect density. Two-dimensional
      assemblies of GO and rGO were formed through electrostatic adsorption at Au
      electrodes, sequentially modified with 11-mercaptoundecanoic acid (MUA) and poly
      diallyldimethylammonium chloride (PDADMAC). The MUA:PDADMAC generates a strong
      blocking layer to the electron-transfer reaction involving the ferri/ferrocyanide
      redox couple. This blocking behaviour is not significantly affected upon
      adsorption of GO. However, adsorption of a sub-monolayer of rGO decreases the
      charge-transfer resistance by more than two orders of magnitude. Analysis of
      cyclic voltammograms and impedance spectra suggests that electron transfer in rGO
      assemblies is mediated by occupied states located just below the redox Fermi
      energy of the probe. These findings are discussed in the context of on-going
      controversies regarding the electrochemical reactivity of sp(2)-carbon basal
      planes.

PMID- 22865796
TI  - Linear combinations of biomarkers to improve diagnostic accuracy with three
      ordinal diagnostic categories.
AB  - Many researchers have addressed the problem of finding the optimal linear
      combination of biomarkers to maximize the area under receiver operating
      characteristic (ROC) curves for scenarios with binary disease status. In
      practice, many disease processes such as Alzheimer can be naturally classified
      into three diagnostic categories such as normal, mild cognitive impairment and
      Alzheimer's disease (AD), and for such diseases the volume under the ROC surface
      (VUS) is the most commonly used index of diagnostic accuracy. In this article, we
      propose a few parametric and nonparametric approaches to address the problem of
      finding the optimal linear combination to maximize the VUS. We carried out
      simulation studies to investigate the performance of the proposed methods. We
      apply all of the investigated approaches to a real data set from a cohort study
      in early stage AD.

PMID- 22865798
TI  - Eight cases of malignant mixed Mullerian tumor (carcinosarcoma) of the uterus:
      findings in SurePathTM cervical cytology.
AB  - Malignant mixed Mullerian tumor (MMMT)/carcinosarcoma is a rare neoplasm of the
      female genital tract characterized by a mixture of epithelial and mesenchymal
      components. There are published reports of conventional cervical smear findings
      in uterine MMMT, but to the best of our knowledge the cytomorphology of MMMT in
      SurePathTM liquid-based cytology samples has not been described. We present a
      series of eight cases of uterine MMMT in SurePathTM cervical samples. The mean
      age of the women was 65.5 years (range, 60-82 years) and the most common
      presenting symptom was postmenopausal bleeding. Three out of the eight cases had
      both epithelial and sarcomatous elements in highly cellular cervical samples. In
      two cases, abnormal glandular cell clusters were closely associated with the
      mesenchymal component. The glandular component was usually represented by three
      dimensional clusters of malignant glandular cells and a dispersed population of
      large, round to oval malignant epithelial cells with single prominent nucleoli.
      Necrosis or tumor diathesis was not seen in any cases. Six out of the eight cases
      were initially reported as adenocarcinoma, endometrial type, and two cases as
      normal. Five cases had an atrophic background and tiny atypical glandular
      clusters that could easily be overlooked. Although cervical sample is not the
      method of choice for primary uterine carcinosarcoma screening, the possibility of
      the same should be kept in mind, when reporting a cervical sample from a woman
      with postmenopausal vaginal bleeding.

PMID- 22865799
TI  - 'Benign invigilation': using appreciative inquiry to reposition clinical risk in
      multi-disciplinary CAMH teams.
AB  - In response to a spate of serious untoward incident enquiries, CAMHS team leaders
      in East London, UK, embarked on a series of clinical risk workshops with staff
      teams. Complementary to what might be called retrospective organisational
      responses to high risk events, these prospective workshops were predicated on the
      idea that risk reduction is increased when individuals in teams are responsive to
      one another, when teams are positively risk-aware and when risk awareness is seen
      as having the capacity to predict what may go wrong in the future.

PMID- 22865800
TI  - Measuring equilibrium bicarbonate concentrations directly in cellular
      mitochondria and in human serum using europium/terbium emission intensity ratios.
AB  - A series of Eu and Tb complexes of four different chiral ligands incorporating an
      azaxanthone sensitiser has been evaluated as probes for the bicarbonate anion.
      Their binding affinities were assessed at ambient pH with bicarbonate, lactate,
      citrate, phosphate and serum albumin. Binding was signalled by modulation of
      circularly polarised luminescence and apparent affinity constants were measured
      by examining changes in emission intensity ratios. Competition experiments show
      that with these species and ATP present at normal physiological values,
      bicarbonate can be determined selectively over the concentration range 10 to 35
      mM. Bicarbonate levels are also reported by using a mixture of Eu and Tb
      complexes of a common ligand, examining the ratio of red/green emitted light.
      These methods have been adapted for the determination of bicarbonate in human
      serum and used for the assessment of mitochondrial levels of bicarbonate in
      several different cell types with confocal microscopy.

PMID- 22865801
TI  - Hydronephrosis and loin pain as a presentation of tubo-ovarian abscess developing
      after Mirena coil removal.
AB  - We present an unusual and complicated case of a 39-year-old woman who was
      admitted three times in hospital over a period of 4&emsp14;weeks, with abdominal
      pain initially and then right loin pain, fever and feeling generally unwell. She
      was investigated on each admission with different diagnoses set each time, but
      only on her last admission due to persisting symptoms, an MRI scan revealed a
      tubo-ovarian abscess associated with pelvic inflammatory disease (PID). We
      believe that the PID had developed secondary to the intrauterine device and a few
      weeks after the removal of the Mirena coil she was diagnosed with a tubo-ovarian
      abscess. As the case unfolds, we will introduce the possible diagnoses and causes
      that were likely to have led to the development of the abscess.

PMID- 22865802
TI  - Idiopathic proliferative verrucous leukoplakia: report of a clinical rarity.

PMID- 22865803
TI  - Neuroretinitis following bull ant sting.
AB  - Cat scratch disease causes the majority of cases of neuroretinitis.
      Neuroretinitis is characterised by clinical features of papillitis, macular
      oedema and macular star. We report a case study of infection with Bartonella
      henselae most likely transmitted by a bull ant sting. The patient presented with
      blurred vision and reduced visual acuity after being stung by an ant in her
      garden some 7 days earlier. Further testing revealed positive serology to B
      henselae and the patient improved with appropriate treatment.

PMID- 22865804
TI  - Palm oil thorn-induced squamous cell carcinoma with underlying burns scar.
AB  - Marjolin's ulcers are malignancies that arise from previously traumatised,
      chronically inflamed or scarred skin. We present a case with childhood burns, who
      had repeated irritation of his forearm skin with palm oil thorns that eventually
      led to malignant change.

PMID- 22865805
TI  - Angiosarcoma of the liver as a cause of fulminant liver failure.
AB  - Primary liver sarcomas make up 2% of all malignant neoplasms of the liver; of
      these, angiosarcoma is the most common type. Primary liver tumours rarely cause
      fulminant hepatic failure (FHF), which is most frequently caused by non
      neoplasmic pathologies. In the case of neoplasms, the most frequent are lymphoma
      and metastatic carcinomas. We describe the case of a 76-year-old man who suffered
      from FHF as a result of a liver angiosarcoma and we present a review of the
      medical literature in which we found only two cases of liver angiosarcomas linked
      to FHF.

PMID- 22865806
TI  - A neurological presentation of intravascular B-cell lymphoma.
AB  - Intravascular B-cell lymphoma is a rare, aggressive subtype of diffuse large B
      cell lymphoma that presents insidiously with symptoms relating to organ
      involvement. We present the case of a male in his late 40s who presented with
      fluctuating neurological symptoms including episodes of altered upper-limb
      sensation, seizures and psychotic phenomena. These symptoms and signs were
      associated with fleeting brain lesions on neuroimaging. A brain biopsy confirmed
      the diagnosis of intravascular B-cell lymphoma and he was treated with CHOP
      chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristine and
      prednisolone). Two years later, he remains well. Timely diagnosis and aggressive
      treatment provides an optimal chance of long-term survival so it is essential to
      recognise early disease characteristics.

PMID- 22865807
TI  - Atropine sulphate: rescue therapy for pyloric stenosis.
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is a common condition which
      presents with non-bilious vomiting and failure to thrive secondary to gastric
      outlet obstruction. In the UK, management is by fluid resuscitation followed by
      pyloromyotomy. Incomplete myotomy complicates 0.3% of cases necessitating further
      surgery and exposing the patient to further risk. Medical management of IHPS with
      antimuscarinics to promote pyloric relaxation is a well-described treatment
      modality that is used as first-line therapy in some countries. The use of this
      technique is limited by the need for extended hospital admission with parenteral
      nutrition administration. We describe a case of IHPS complicated by incomplete
      pyloromyotomy and subsequently managed successfully by atropine sulphate therapy.

PMID- 22865808
TI  - Mediastinal huge non-Hodgkin's lymphoma causing compression of the main pulmonary
      artery trunk.

PMID- 22865809
TI  - Another case of chest pain on the acute medical take!
AB  - A physiologically fit 91-year-old gentleman presented with sudden onset chest
      pain, breathlessness and cardiovascular compromise associated with vomiting. He
      was treated for renal colic, community-acquired pneumonia and pulmonary embolism
      before a formal diagnosis of Boerhaave's syndrome was made. The patient was
      prepared for emergency surgery, unfortunately his condition deteriorated rapidly
      and he was subsequently managed conservatively. He died 2&emsp14;days later.
      Diagnosis and treatment of Boerhaave's syndrome are often delayed. Treatment
      options for Boerhaave's syndrome include conservative measures, endoscopic
      interventions and surgery. Chest pain is a common presentation on the acute
      medical take. Boerhaave's syndrome is a rare cause of chest pain, which may mimic
      other conditions but should not be missed due a high death rate.

PMID- 22865810
TI  - Right ventricular hypertrabeculation due to right heart failure after left
      ventricular assist device implantation.

PMID- 22865811
TI  - Spontaneous mesenteric haematoma; diagnosis and management.
AB  - Spontaneous mesenteric haematomas are rare. They have been reported to be
      associated with coagulopathies, connective tissue disorders, past trauma,
      arteriopathy and pancreatitis. However, some cases have been reported in which
      there is no apparent underlying aetiology. Here we report such a case and we
      review the literature that discusses optimal diagnosis and management. In this
      case, spontaneous haemostasis occurred by intra-abdominal tamponade and the
      regression of the haematoma was monitored with regular imaging.

PMID- 22865812
TI  - Congenital omental cyst.
AB  - Congenital omental cysts are rare intra-abdominal pathology, which are difficult
      to diagnose preoperatively; as such a high index of suspicion is required for
      accurate preoperative diagnosis. We present a case of congenital omental cyst in
      a 3-year-old girl who presented with huge abdominal distension. We performed
      diagnostic examinations including ultrasonography and CT of the abdomen. An
      omental cyst was diagnosed because of its position and connection to the
      surrounding tissues. She was operated and cyst was excised completely.
      Histological examination revealed an omental cyst with endothelial lining and
      haemorrhagic fluid inside. She had an uneventful recovery and doing well, without
      recurrence at follow-up of 24&emsp14;months. Clinicians must rigorously pursue a
      preoperative diagnosis, as it may prevent a surprise upon laparotomy and result
      in proper management.

PMID- 22865813
TI  - Wrapping and dispersion of multiwalled carbon nanotubes improves electrical
      conductivity of protein-nanotube composite biomaterials.
AB  - Composites of extracellular matrix proteins reinforced with carbon nanotubes have
      the potential to be used as conductive biopolymers in a variety of biomaterial
      applications. In this study, the effect of functionalization and polymer wrapping
      on the dispersion of multiwalled carbon nanotubes (MWCNT) in aqueous media was
      examined. Carboxylated MWCNT were wrapped in either Pluronic((r)) F127 or
      gelatin. Raman spectroscopy and X-ray photoelectron spectroscopy showed that
      covalent functionalization of the pristine nanotubes disrupted the carbon lattice
      and added carboxyl groups. Polymer and gelatin wrapping resulted in increased
      surface adsorbed oxygen and nitrogen, respectively. Wrapping also markedly
      increased the stability of MWCNT suspensions in water as measured by settling
      time and zeta potential, with Pluronic((r))-wrapped nanotubes showing the
      greatest effect. Treated MWCNT were used to make 3D collagen-fibrin-MWCNT
      composite materials. Carboxylated MWCNT resulted in a decrease in construct
      impedance by an order of magnitude, and wrapping with Pluronic((r)) resulted in a
      further order of magnitude decrease. Functionalization and wrapping also were
      associated with maintenance of fibroblast function within protein-MWCNT
      materials. These data show that increased dispersion of nanotubes in protein
      MWCNT composites leads to higher conductivity and improved cytocompatibility.
      Understanding how nanotubes interact with biological systems is important in
      enabling the development of new biomedical technologies.

PMID- 22865814
TI  - Multi-functional integration of organic field-effect transistors (OFETs):
      advances and perspectives.
AB  - Multi-functional organic field-effect transistors (OFETs), an emerging focus of
      organic optoelectronic devices, hold great potential for a variety of
      applications. This report introduces recent progress on multi-functional OFETs
      including OFETs based sensors, phototransistors, light-emitting transistors,
      memory cells, and magnetic field-effect OFETs. Key strategies towards multi-
      functional integration of OFETs, which involves the exploration of functional
      materials, interfaces modifications, modulation of condensed structures,
      optimization of device geometry, and device integration, are summarized.
      Furthermore, remaining challenges and perspectives are discussed, giving a
      comprehensive overview of multi-functional OFETs.

PMID- 22865815
TI  - Hospital medicine in the internal medicine clerkship: results from a national
      survey.
AB  - BACKGROUND: Hospital medicine is growing rapidly. This changing inpatient work
      force has had consequences on medical education, with an increasing hospitalist
      presence in resident and student training. Initially met with apprehension, there
      is growing literature to suggest that hospitalists are perceived to be more
      effective clinical teachers than non-hospitalists. However, the extent to which
      hospitalists are involved in teaching Internal Medicine (IM) to medical students
      is not known. METHODS: In order to determine the role of hospitalists in medical
      student education within the United States and Canada, we queried clerkship
      directors in Internal Medicine as part of the 2010 annual Clerkship Directors in
      Internal Medicine (CDIM) survey. In June 2010, CDIM surveyed its North American
      institutional members, which represent 110 of 143 Departments of Medicine in the
      US and Canada. RESULTS: Eight-two of 107 departments responded to the survey
      (77%). Seventy-five (91%) indicated that hospitalists served as teaching
      attendings at their teaching hospital. In twenty-two (27%) IM departments, 75% to
      100% of students rotate with a hospitalist during their IM clerkships. Thirty
      three (42%) departments report that students are directly supervised by in-house
      hospitalists during their nighttime call requirements. Sixty-six (81%) indicated
      that academic hospitalists hold educational administrative positions.
      Hospitalists are significantly less likely to have additional clinical commitment
      as compared to non-hospitalist teaching attendings (16% vs 53%, (chi 21df = 33.1;
      P < 0.0001). CONCLUSIONS: Hospitalists are involved in medical student education
      in the large majority of Departments of Internal Medicine throughout the US and
      Canada, reflecting the growth of hospital medicine nationally.

PMID- 22865816
TI  - The effectiveness of national guidance in changing analgesic prescribing in
      primary care from 2002 to 2009: an observational database study.
AB  - BACKGROUND: Numerous national guidelines have been issued to assist general
      practitioners' safe analgesic prescribing. Their effectiveness is unclear. The
      objective of this study was to examine trends in general practitioners'
      prescribing behaviour in relation to national guidelines. METHODS: This was a
      retrospective observational database study of registered adult patients
      prescribed an analgesic (2002-2009) from the Consultations in Primary Care
      Archive--12 North Staffordshire general practices. Prescribing guidance from the
      UK Medicines Regulatory Health Authority (MHRA) regarding non-steroidal anti
      inflammatory drugs (NSAIDs) and co-proxamol, and the National Institute for
      Health and Clinical Excellence (NICE) osteoarthritis (OA) management guidelines
      were considered. Analgesic prescribing rates were examined, arranged according to
      a classification of six equipotent medication groups: (1) basic analgesics; (2)
      (5) increasingly potent opioids and (6) NSAIDs. In each quarter from 2002 to
      2009, the number of patients per 10,000 registered population receiving a
      prescription for the first time from each group was determined. Quarters
      associated with significant changes in the underlying prescribing trend were
      determined using joinpoint regression. RESULTS: A significant decrease in
      incident co-proxamol and Cox-2 prescribing occurred around the time of the first
      MHRA advice to stop using them and were rarely prescribed thereafter. The new
      prescribing of weak analgesics (e.g., co-codamol 8/500) increased at this same
      time. Initiating topical NSAIDs significantly increased around the time of the
      NICE OA guidelines. CONCLUSIONS: Significant prescribing changes occurred when
      national advice and guidelines were issued. The effectiveness of this advice may
      vary depending upon the content and method of dissemination. Further evaluation
      of the optimal methods for delivering prescribing guidance is required.

PMID- 22865817
TI  - Sample size in cluster-randomized trials with time to event as the primary
      endpoint.
AB  - In cluster-randomized trials, groups of individuals (clusters) are randomized to
      the treatments or interventions to be compared. In many of those trials, the
      primary objective is to compare the time for an event to occur between randomized
      groups, and the shared frailty model well fits clustered time-to-event data.
      Members of the same cluster tend to be more similar than members of different
      clusters, causing correlations. As correlations affect the power of a trial to
      detect intervention effects, the clustered design has to be considered in
      planning the sample size. In this publication, we derive a sample size formula
      for clustered time-to-event data with constant marginal baseline hazards and
      correlation within clusters induced by a shared frailty term. The sample size
      formula is easy to apply and can be interpreted as an extension of the widely
      used Schoenfeld's formula, accounting for the clustered design of the trial.
      Simulations confirm the validity of the formula and its use also for non-constant
      marginal baseline hazards. Findings are illustrated on a cluster-randomized trial
      investigating methods of disseminating quality improvement to addiction treatment
      centers in the USA.

PMID- 22865818
TI  - Fibrin-chitosan composite substrate for in vitro culture of chondrocytes.
AB  - The aim of this study was to develop a biocompatible monolayer substrate based on
      fibrin and chitosan for in vitro culture of chondrocytes. Fibrin-chitosan
      composite substrates combined the proved cell adhesion properties of fibrin with
      the hydrophilicity and poor adhesion capacity of chitosan. Chitosan microspheres
      were produced by coacervation method, agglomerated within a fibrin network and
      subsequently crosslinked with genipin. The composite substrate was stable for 28
      days of culture due to the high crosslinking density. Human chondrocytes cultured
      on the composite substrate were viable during the culture period. At the end of
      culture time (28 days) the composite substrate showed low cellular proliferation,
      41% more collagen type II and 13% more production of sulfated glycosaminoglycans
      with respect to the amounts found at 14 days. The study revealed that
      dedifferentiated chondrocytes cultured in monolayer on the composite substrate
      can re-acquire characteristics of differentiated cells without using three
      dimensional substrates or chondrogenic media.

PMID- 22865819
TI  - Mutations of ANK3 identified by exome sequencing are associated with autism
      susceptibility.
AB  - Autism spectrum disorders (ASDs) are common neurodevelopmental disorders with a
      strong genetic etiology. However, due to the extreme genetic heterogeneity of
      ASDs, traditional approaches for gene discovery are challenging. Next-generation
      sequencing technologies offer an opportunity to accelerate the identification of
      the genetic causes of ASDs. Here, we report the results of whole-exome sequence
      in a cohort of 20 ASD patients. By extensive bioinformatic analysis, we
      identified novel mutations in seven genes that are implicated in synaptic
      function and neurodevelopment. After sequencing an additional 47 ASD samples, we
      identified three different missense mutations in ANK3 in four unrelated ASD
      patients, one of which, c.4705T>G (p.S1569A), is a de novo mutation. Given the
      fact that ANK3 has been shown to strongly associate with schizophrenia and
      bipolar disorder, our findings support an association between ANK3 mutations and
      ASD susceptibility and imply a shared molecular pathophysiology between ASDs and
      other neuropsychiatric disorders.

PMID- 22865820
TI  - Trajectories of late-life change in God-mediated control.
AB  - OBJECTIVE: To track within-individual change during late life in the sense of
      personal control and God-mediated control (the belief that one can work
      collaboratively with God to achieve one's goals and exercise control over life
      events) and to evaluate the hypothesis that this element of religion is related
      to declining personal control. METHOD: A longitudinal survey representative of
      older White and Black adults in the United States tracked changes in personal and
      God-mediated control in four waves over the course of 7 years. RESULTS: Growth
      curve analysis found that the pattern of change differed by race. White adults
      had less sense of God-mediated control at younger ages, which increased among
      those who were highly religious but decreased among those who were less
      religious. Black adults had higher God-mediated control, which increased over
      time among those with low personal control. DISCUSSION: These results indicate
      that God-mediated control generally increases during older adulthood, but that
      its relationships with personal control and religious commitment are complex and
      differ between Black and White adults.

PMID- 22865821
TI  - Empathic concern and perspective taking: linear and quadratic effects of age
      across the adult life span.
AB  - OBJECTIVE: We investigated linear and quadratic effects of age on self-reported
      empathy in three large cross-sectional samples of American adults aged 18-90
      years. METHOD: Participants completed subscales of the Interpersonal Reactivity
      Index (Davis, 1983), allowing us to independently assess an emotional component
      of empathy ("empathic concern") and a cognitive component of empathy
      ("perspective taking") across the adult life span. RESULTS: For both measures and
      in all three samples, we found evidence for an inverse-U-shaped pattern across
      age: Middle-aged adults reported higher empathy than both young adults and older
      adults. We also found a consistent gender difference: Women reported more empathy
      than men. We did not find systematic differences by ethnicity. However, neither
      gender nor ethnicity interacted with age effects. DISCUSSION: We discuss the
      inverse-U-shaped age pattern, in terms of aging versus cohort influences, and how
      it complements and extends the existing literature on empathy and age.

PMID- 22865823
TI  - Age-related differences in processing face configuration: the importance of the
      eye region.
AB  - OBJECTIVES: Recent research suggests that older adults have difficulties with
      aspects of configural face processing. The present study examined whether age
      related declines in sensitivity to configural face information are dependent on
      the face region in which configural changes occur. METHOD: Younger and older
      adults completed a face-matching task that required the detection of configural
      manipulations to either the eye or the mouth regions of target faces. RESULTS:
      Age-related declines in the ability to detect configural changes were found when
      the eye region of the face was modified. Importantly, no age-related differences
      were evident when perceiving similar changes to the mouth region. DISCUSSION:
      Taken together, these findings suggest that age-related differences in
      sensitivity to configural information are specific to the eye region of the face.
      The potential implications of these findings for age-related difficulties in
      interpreting social cues from the eyes are discussed.

PMID- 22865822
TI  - Cognitive function as a prospective predictor of falls.
AB  - OBJECTIVE: This study examined speed of processing, executive functioning, and
      psychomotor speed as independent prospective predictors of falls and recurrent
      falls across 3 years. METHOD: The participants were 509 community-dwelling older
      adults. Measures of speed of processing, executive function, psychomotor speed,
      and known risk factors of falling were included in correlation and logistic
      regression analyses. RESULTS: Poor executive function (Trail Making Test), slower
      speed of processing (Digit Symbol Substitution [DSS] Test), and slower
      psychomotor speed (Digit Symbol Copy Test) were significantly associated with
      falls. Poor executive function and speed of processing performance (Stroop Test,
      Trail Making Test, and DSS Test) as well as slower psychomotor speed were
      significantly related to recurrent falls. Logistic regression results indicated
      that only medication use, far visual acuity, and psychomotor speed were
      significant independent predictors of falls. Regarding recurrent falls, being
      white, medication use, and balance were significant predictors. DISCUSSION:
      Although cognitive measures at baseline were significantly associated with falls
      and recurrent falls at follow-up, these measures did not predict falling after
      considering known risk factors of falls and psychomotor speed. Thus, it may be
      that simple measures of psychomotor speed are more salient predictors of falls
      than cognitive measures.

PMID- 22865824
TI  - A cross-national comparison of reminiscence functions between Canadian and
      Israeli older adults.
AB  - OBJECTIVES: Recently, a model of reminiscence and well-being has emerged in which
      reminiscence functions have been shown to predict both the mental and physical
      health of middle-aged and older adults. Yet this model has thus far been verified
      only with North American, Western European, and Australian participants. This
      study was undertaken to compare the latent structure of responses between
      Canadian and Israeli older adults to ascertain if 8 distinct reminiscence
      functions map onto 3 second-order factors which, in turn, contribute
      significantly to measurement of an overarching reminiscence latent construct.
      METHOD: For this study, 336 English Canadian and 206 Jewish Israeli adults more
      than 49 years of age provided responses for this study via an Internet website
      constructed specifically for this study. RESULTS: Our findings demonstrate the
      psychometric equivalence as well as various cross-cultural differences in the
      relative strength of association between latent constructs (boredom reduction,
      bitterness revival, identity, and the overall contribution of self-negative
      functions to overall reminiscence). DISCUSSION: We discuss various historical and
      geo-political factors that may account for these differences. For instance,
      recurrent war, ongoing terror, and regional instability make living and aging in
      Israel distinct from Canada. This model of reminiscence functions would appear
      sufficiently sensitive to capture cross-national differences.

PMID- 22865825
TI  - Working memory and the strategic control of attention in older and younger
      adults.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of aging on
      the strategic control of attention and the extent to which this relationship is
      mediated by working memory capacity (WMC). This study also sought to investigate
      boundary conditions wherein age differences in selectivity may occur. METHOD:
      Across 2 studies, the value-directed remembering task used by Castel and
      colleagues (Castel, A. D., Balota, D. A., & McCabe, D. P. (2009). Memory
      efficiency and the strategic control of attention at encoding: Impairments of
      value-directed remembering in Alzheimer's Disease. Neuropsychology, 23, 297-306)
      was modified to include value-directed forgetting. Study 2 incorporated valence
      as an additional task demand, and age differences were predicted in both studies
      due to increased demands of controlled processing. Automated operation span and
      Stroop span were included as working memory measures, and working memory was
      predicted to mediate performance. RESULTS: Results confirmed these predictions,
      as older adults were less efficient in maximizing selectivity scores when high
      demands were placed on selectivity processes, and working memory was found to
      mediate performance on this task. DISCUSSION: When list length was increased from
      previous studies and participants were required to actively forget negative-value
      words, older adults were not able to selectively encode high-value information to
      the same degree as younger adults. Furthermore, WMC appears to support the
      ability to selectively encode information.

PMID- 22865826
TI  - Scalable fabrication of silicon nanotubes and their application to energy
      storage.
AB  - The facile synthesis of silicon nanotubes using a surface sol-gel reaction on
      pyridine nanowire templates is reported and their performance for energy storage
      is investigated. Organic-inorganic hybrid pyridine/silica core-shell nanowires
      prepared using surface sol-gel reaction were converted to silica nanotubes by
      pyrolysis in air; this was followed by the reduction to silicon nanotubes via
      magnesiothermic reaction. The electrochemical activity of the obtained silicon
      nanotubes showed excellent cycle stability, suggesting that the hollow one
      dimensional structure would be a good candidate for a high-capacity anode for a
      lithium ion battery.

PMID- 22865827
TI  - Hospitalist-led medicine emergency department team: associations with throughput,
      timeliness of patient care, and satisfaction.
AB  - BACKGROUND: Admitted patients boarding in the emergency department (ED) leads to
      hospital diversion. Active bed management and care for boarded patients can
      improve throughput. We developed a hospital medicine ED (HMED) team to
      participate in active bed management, and to care for boarded patients, to
      decrease diversion and improve throughput. METHODS: An HMED team was created to
      participate in active bed management and to care for boarded patients. The HMED
      team worked with the ED, nursing supervisors, and medical floors to manage
      inpatient beds. The primary outcome was percentage of hours of diversion
      attributed to lack of bed capacity. Secondary outcomes included the proportion of
      patients discharged within 8 hours of transfer to a medical floor, and the
      proportion of patients discharged from the ED. Promptness of clinical care was
      measured by rounding times. Satisfaction was obtained via survey. RESULTS: There
      was a relative reduction of diversion due to medicine bed capacity of 27% (4.5%
      3.3%; P < 0.01), a relative reduction in the percentage of patients transferred
      to a medicine floor and discharged within 8 hours of 67% (1.5%-0.5%; P < 0.01),
      and a relative increase in the number of discharges from the ED of admitted
      medicine patients of 61% (4.9%-7.9%; P < 0.001). Boarded admitted patients were
      rounded upon 2 hours earlier (P < 0.0001) by the HMED team. Satisfaction with the
      HMED team was high. CONCLUSION: An HMED team can improve patient flow and
      decrease ED diversion while providing more timely care to patients boarded in the
      ED.

PMID- 22865828
TI  - Designing multitarget anti-inflammatory agents: chemical modulation of the
      lumiracoxib structure toward dual thromboxane antagonists-COX-2 inhibitors.
AB  - A series of lumiracoxib derivatives were designed to explore the influence of
      isosteric substitution on balancing COX-2 inhibition and thromboxane A(2) 
      prostanoid (TP) receptor antagonism. The compounds were synthesized through a
      copper-catalyzed coupling procedure and characterized for their pK(a)  values. TP
      receptor antagonism was assessed on human platelets; COX-2 inhibition was
      determined on human isolated monocytes and human whole blood. TPalpha receptor
      binding of the most promising compounds was evaluated through radioligand binding
      assays. Some of the isosteric substitutions at the carboxylic acid group afforded
      compounds with improved TP receptor antagonism; of these, a tetrazole derivative
      retained good COX-2 inhibitory activity and selectivity. The identification of
      this tetrazole acting as a balanced dual-acting compound in human whole blood,
      along with SAR analysis of the synthesized lumiracoxib derivatives, might
      contribute to the rational design of a new class of cardioprotective anti
      inflammatory agents.

PMID- 22865829
TI  - Altered sperm chromatin structure in mice exposed to sodium fluoride through
      drinking water.
AB  - This study investigated the effects of sodium fluoride (NaF) on sperm
      abnormality, sperm chromatin structure, protamine 1 and protamine 2 (P1 and P2)
      mRNA expression, and histones expression in sperm in male mice. NaF was orally
      administrated to male mice at 30, 70, and 150 mg/l for 49 days (more than one
      spermatogenic cycle). Sperm head and tail abnormalities were significantly
      enhanced at middle and high doses. Similarly, sperm chromatin structure was also
      adversely affected by NaF exposure, indicating DNA integrity damage. Furthermore,
      middle and high NaF significantly reduced the mRNA expressions of P1 and P2, and
      P1/P2 ratio, whereas the sperm histones level was increased, suggesting the
      abnormal histone-protamine replacement. Therefore, we concluded that the
      mechanism by which F induced mice sperm abnormality and DNA integrity damage may
      involved in the alterations in P1, P2, and histones expression in sperm of mice.

PMID- 22865830
TI  - Chinese adaptation and validation of the patellofemoral pain severity scale.
AB  - OBJECTIVE: This study validated the Patellofemoral Pain Severity Scale translated
      into Chinese. DESIGN AND SETTING: The Chinese Patellofemoral Pain Severity Scale
      was translated from the original English version following standard forward and
      backward translation procedures recommended by the International Society for
      Pharmacoeconomics and Outcomes Research. The survey was then conducted in
      clinical settings by a questionnaire comprising the Chinese Patellofemoral Pain
      Severity Scale, Kujala Scale and Western Ontario and McMaster Universities
      (WOMAC) Osteoarthritis Index. SUBJECTS: Eighty-four Chinese reading patients with
      patellofemoral pain were recruited from physical therapy clinics. MAIN MEASURES:
      Internal consistency of the translated instrument was measured by Cronbach alpha.
      Convergent validity was examined by Spearman rank correlation coefficient (rho)
      tests by comparing its score with the validated Chinese version of the Kujala
      Scale and the WOMAC Osteoarthritis Index while the test-retest reliability was
      evaluated by administering the questionnaires twice. RESULTS: Cronbach alpha
      values of individual questions and their overall value were above 0.85. Strong
      association was found between the Chinese Patellofemoral Pain Severity Scale and
      the Kujala Scale (rho = -0.72, p < 0.001). Moderate correlation was also found
      between Chinese Patellofemoral Pain Severity Scale with the WOMAC Osteoarthritis
      Index (rho = 0.63, p < 0.001). Excellent test-retest reliability (Intraclass
      correlation coefficient = 0.98) was demonstrated. CONCLUSIONS: The Chinese
      translated version of the Patellofemoral Pain Severity Scale is a reliable and
      valid instrument for patients with patellofemoral pain.

PMID- 22865831
TI  - A randomized controlled pilot study assessing the feasibility of combined motor
      cognitive training and its effect on gait characteristics in the elderly.
AB  - OBJECTIVE: (1) To develop a motor-cognition training programme; (2) to evaluate
      the ability to recruit and retain elderly people; (3) to assess the effects of
      the interventions. DESIGN: Pilot randomized controlled trial. SETTING: Assisted
      living facility. PARTICIPANTS: Sixteen subjects (11 female) living in an assisted
      living facility were randomized to a motor or motor-cognition group.
      INTERVENTIONS: Both groups received machine-driven strength training and balance
      exercises for 45 minutes, twice weekly, for 12 weeks. In addition, the motor
      cognition group received computerized training for attention 3-5 times per week
      for 10 weeks. MAIN OUTCOME MEASURES: Baseline and post-intervention (12 weeks)
      assessments focused on recruitment, attrition and adherence. Secondary outcome
      measures assessed dual-task costs of gait (velocity, cadence, step time, step
      length), expanded timed get-up-and-go, falls efficacy and reaction time. RESULTS:
      Of 35 subjects initially approached, 16 started and 14 completed the study,
      resulting in 46% recruitment, 19% attrition and >80% adherence rates. There is
      more evidence of altered levels in the motor-cognitive treatment group with
      significant differences in average change for fear of falling (P = 0.017) and
      foot reaction time (P = 0.046). No statistical significance was reached for gait
      parameters. CONCLUSIONS: Motor-cognition training is feasible and shows trends to
      stronger improvement in walking and reaction time. The application in a main
      study is deemed feasible. A minimum of +/- 55 subjects per group are required to
      achieve a power of 80% at the 5% level of significance based on step length and
      considering the expectable attrition rate in a required larger scale study.

PMID- 22865832
TI  - Biofunctionalization of titanium surface with multilayer films modified by
      heparin-VEGF-fibronectin complex to improve endothelial cell proliferation and
      blood compatibility.
AB  - In-stent restenosis and subsequent thrombosis remain a significant complication
      following the implantation of coronary stents. Different approaches have been
      used in developing novel coronary stents to protect against thrombosis and
      minimize restenosis. In the present study, we designed a biomacromolecular layer
      by-layer coating with heparin, vascular endothelial growth factor (VEGF), and
      fibronectin onto nickel-free titanium surface to improve blood compatibility and
      endothelial cell proliferation. The multilayer assembling process was monitored
      by water contact angle and surface plasmon resonance, respectively. With
      increasing the number of layers, the deposition of polyelectrolyte as self
      assembled ultrathin multilayer films showed linear growth of absorbance. In vitro
      blood compatibility results revealed that the fabricated layers prolonged
      activated partial thrombin time and prothrombin time, reduced platelets
      activation and aggregation, and reduced blood hemolysis rate. Cell adhesion and
      growth results showed that the assembled multilayer films significantly promoted
      cell attachment and growth, and the endothelialization property of the multilayer
      films was preferable compared with the untreated titanium disk. In conclusion,
      these results suggest that titanium surface modification using biofunctional
      multilayer films composed of heparin, VEGF, and fibronectin may serve as a
      potential approach to inhibit thrombosis and promote re-endothelialization of
      cardiovascular stents.

PMID- 22865833
TI  - Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of
      facial dysmorphism, intellectual disability, and primordial dwarfism.
AB  - Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition.
      Various molecular mechanisms are known to underlie the disease including impaired
      mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response,
      defective spliceosomal machinery, and abnormal replication licensing. Here, we
      describe a syndromic form of PD associated with severe intellectual disability
      and distinct facial features in a large multiplex Saudi family. Analysis reveals
      a novel underlying mechanism for PD involving depletion of 7SK, an abundant
      cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show
      that 7SK levels are tightly linked to LARP7 expression across cell lines, and
      that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is
      known to influence the expression of a wide array of genes through its inhibitory
      effect on the positive transcription elongation factor b (P-TEFb) as well as its
      competing role in HMGA1-mediated transcriptional regulation. This study documents
      a critical role played by ncRNA in human development and adds to the growing list
      of molecular mechanisms that, when perturbed, converge on the PD phenotype.

PMID- 22865834
TI  - Synthesis and biological evaluation of CTP synthetase inhibitors as potential
      agents for the treatment of African trypanosomiasis.
AB  - Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were
      designed as potential new trypanocidal agents. The inhibitory activity against
      CTPS can be improved by increasing molecular complexity, by inserting groups able
      to establish additional interactions with the binding pocket of the enzyme. This
      strategy has been pursued with the synthesis of alpha-amino-substituted analogues
      of Acivicin and N1-substituted pyrazoline derivatives. In general, there is
      direct correlation between the enzymatic activity and the in vitro anti
      trypanosomal efficacy of the derivatives studied here. However, this cannot be
      taken as a general rule, as other important factors may play a role, notably the
      ability of uptake/diffusion of the molecules into the trypanosomes.

PMID- 22865835
TI  - The making of a public health problem: multi-drug resistant tuberculosis in
      India.
AB  - This paper examines how actors construct the public problem of multi-drug
      resistant tuberculosis (MDR-TB) in India. MDR-TB has been framed by the World
      Health Organization as a pressing, global public health problem. The responses to
      MDR-TB are complicated as treatment takes longer and is more expensive than
      routine TB treatment. This is particularly problematic in countries, such as
      India, with high patient loads, a large and unregulated private sector, weak
      health systems and potentially high numbers of MDR-TB cases. This paper analyses
      how actors struggle for control over ownership, causal theories and political
      responsibility of the public problem of MDR-TB in India. It combines Gusfield's
      theory on the construction of public problems with insights from literature on
      the social construction of diseases and on medical social control. It highlights
      that there are flexible definitions of public problems, which are negotiated
      among actor groups and which shift over time. The Indian government has shifted
      its policy in recent years and acknowledged that MDR-TB needs to be dealt with
      within the TB programme. The study results reveal how the policy shift happened,
      why debates on the construction of MDR-TB as a public problem in India continue,
      and why actors with alternative theories than the government do not succeed in
      their lobbying efforts. Two main arguments are put forward. First, the
      construction of the public problem of MDR-TB in India is a social and political
      process. The need for representative data, international influence and politics
      define what is controllable. Second, the government seems to be anxious to
      control the definition of India's MDR-TB problem. This impedes an open, critical
      and transparent discussion on the definition of the public problem of MDR-TB,
      which is important in responding flexibly to emerging public health challenges. 

PMID- 22865836
TI  - Development and validation of stability-indicating assay method by UPLC for a
      fixed dose combination of atorvastatin and ezetimibe.
AB  - A stability-indicating ultra-performance liquid chromatography method was
      developed and validated for the simultaneous determination of a fixed dose
      combination of atorvastatin and ezetimibe in bulk drugs. The developed method was
      successfully applied to the simultaneous quantitative analysis of the combination
      drugs in tablet. The chromatographic separation was performed on a Kromasil
      Eternity C18 UHPLC column (2.5 um, 2.1 * 50 mm) using a gradient elution of
      acetonitrile and ammonium acetate buffer (pH 6.70; 0.01M) as the mobile phase at
      a flow rate of 0.2 mL/min with column oven temperature of 40 degrees C.
      Ultraviolet detection was performed at 245 nm. Total run time was 5 min, within
      which the primary compounds and their degradation products were separated. The
      method was validated for accuracy, repeatability, reproducibility and robustness.
      Linearity, limit of detection and limit of quantitation were established for
      atorvastatin and ezetimibe.

PMID- 22865837
TI  - A stability-indicating HPLC method for the determination of bazedoxifene acetate
      and its related substances in active pharmaceutical ingredient.
AB  - A simple, cost effective, stability-indicating reversed-phase high-performance
      liquid chromatography method was developed for the quantitative determination of
      bazedoxifene acetate (BAZ) drug substance in the presence of its impurities and
      degradation products. The method was developed using an X-terra RP-18, 150 * 4.6
      mm, 3.5 MUm column with a mobile phase containing solvent A, a mixture of 10 mM
      K(2)HPO(4) (pH 8.3) and acetonitrile in the ratio of 70:30 (v/v); and solvent B,
      a mixture of water and acetonitrile in the ratio 10:90 (v/v). The eluted
      compounds were monitored at 220 nm, and within a short run time of 18 min, BAZ
      and its impurities were satisfactorily separated with resolution more than 2.0.
      BAZ was subjected to stress degradation and found to be sensitive towards acidic,
      basic, oxidative, thermal and hydrolytic stress conditions and stable in photo
      degradation conditions. The degradation products were well resolved from BAZ peak
      and its impurities; the mass balance in each case was more than 99.5%, proving
      the stability-indicating power of the method. The developed method was validated
      as per International Conference on Harmonization guidelines with respect to
      specificity, linearity (correlation coefficient > 0.9994), limit of detection,
      limit of quantification, accuracy (recovery range 96.3 to 102.1%), precision
      (relative standard deviation < 2.8%) and robustness.

PMID- 22865838
TI  - A simple sample preparation method for measuring amoxicillin in human plasma by
      hollow fiber centrifugal ultrafiltration.
AB  - A simple sample preparation method has been developed for the determination of
      amoxicillin in human plasma by hollow fiber centrifugal ultrafiltration (HF-CF
      UF). A 400-MUL plasma sample was placed directly into the HF-CF-UF device, which
      consisited of a slim glass tube and a U-shaped hollow fiber. After centrifugation
      at 1.25 * 10(3) g for 10 min, the filtrate was withdrawn from the hollow fiber
      and 20 uL was directly injected into the high-performance liquid chromatography
      (HPLC) for analysis. The calibration curve was linear over the range of 0.1-20
      ug/mL (r = 0.9996) and the limit of detection was as low as 0.025 ug/mL. The
      average recovery and absolute recovery were 99.9% and 84.5%, respectively. Both
      the intra-day and inter-day precisions (relative standard deviation) were less
      than 3.1% for three concentrations (0.25, 2.5 and 10 ug/mL). The sample
      preparation process was simplified. Only after a single centrifugal
      ultrafiltration can the filtrate be injected directly into HPLC. The present
      method is simple, sensitive and accurate. It could be effective for the analysis
      of biological samples with high protein contents, especially for the
      biopharmaceutical analysis of drugs that use traditional isolation techniques for
      sample preparation such as the protein precipitation method.

PMID- 22865839
TI  - Some thoughts on sample size: a Bayesian-frequentist hybrid approach.
AB  - BACKGROUND: Traditional calculations of sample size do not formally incorporate
      uncertainty about the likely effect size. Use of a normal prior to express that
      uncertainty, as recently recommended, can lead to power that does not approach 1
      as the sample size approaches infinity. PURPOSE: To provide approaches for
      calculating sample size and power that formally incorporate uncertainty about
      effect size. The relevant formulas should ensure that power approaches one as
      sample size increases indefinitely and should be easy to calculate. METHODS: We
      examine normal, truncated normal, and gamma priors for effect size
      computationally and demonstrate analytically an approach to approximating the
      power for a truncated normal prior. We also propose a simple compromise method
      that requires a moderately larger sample size than the one derived from the fixed
      effect method. RESULTS: Use of a realistic prior distribution instead of a fixed
      treatment effect is likely to increase the sample size required for a Phase 3
      trial. The standard fixed effect method for moving from estimates of effect size
      obtained in a Phase 2 trial to the sample size of a Phase 3 trial ignores the
      variability inherent in the estimate from Phase 2. Truncated normal priors appear
      to require unrealistically large sample sizes while gamma priors appear to place
      too much probability on large effect sizes and therefore produce unrealistically
      high power. LIMITATIONS: The article deals with a few examples and a limited
      range of parameters. It does not deal explicitly with binary or time-to-failure
      data. CONCLUSIONS: Use of the standard fixed approach to sample size calculation
      often yields a sample size leading to lower power than desired. Other natural
      parametric priors lead either to unacceptably large sample sizes or to
      unrealistically high power. We recommend an approach that is a compromise between
      assuming a fixed effect size and assigning a normal prior to the effect size.

PMID- 22865840
TI  - Origin and fate of the 3' ends of single-stranded DNA generated by conjugal
      transfer of plasmid R1162.
AB  - During conjugation, a single strand of DNA is cleaved at the origin of transfer
      (oriT) by the plasmid-encoded relaxase. This strand is then unwound from its
      complement and transferred in the 5'-to-3' direction, with the 3' end likely
      extended by rolling-circle replication. The resulting, newly synthesized oriT
      must then be cleaved as well, prior to recircularization of the strand in the
      recipient. Evidence is presented here that the R1162 relaxase contains only a
      single nucleophile capable of cleaving at oriT, with another molecule therefore
      required to cleave at a second site. An assay functionally isolating this second
      cleavage shows that this reaction can take place in the donor cell. As a result,
      there is a flux of strands with free 3' ends into the recipient. These ends are
      susceptible to degradation by exonuclease I. The degree of susceptibility is
      affected by the presence of an uncleaved oriT within the strand. A model is
      presented where these internal oriTs bind and trap the relaxase molecule
      covalently bound to the 5' end of the incoming strand. Such a mechanism would
      result in the preferential degradation of transferred DNA that had not been
      properly cleaved in the donor.

PMID- 22865841
TI  - Phenotype switching is a natural consequence of Staphylococcus aureus
      replication.
AB  - The pathogen Staphylococcus aureus undergoes phenotype switching in vivo from its
      normal colony phenotype (NCP) to a slow-growing, antibiotic-resistant small
      colony-variant (SCV) phenotype that is associated with persistence in host cells
      and tissues. However, it is not clear whether phenotype switching is the result
      of a constitutive process that is selected for under certain conditions or is
      triggered by particular environmental stimuli. Examination of cultures of diverse
      S. aureus strains in the absence of selective pressure consistently revealed a
      small gentamicin-resistant SCV subpopulation that emerged during exponential
      phase NCP growth and increased in number until NCP stationary phase. Treatment of
      replicating bacteria with the antibiotic gentamicin, which inhibited NCP but not
      SCV replication, resulted in an initial decrease in SCV numbers, demonstrating
      that SCVs arise as a consequence of NCP replication. However, SCV population
      expansion in the presence of gentamicin was reestablished by selection of
      phenotype-stable SCVs and subsequent SCV replication. In the absence of selective
      pressure, however, phenotype switching was bidirectional and occurred at a high
      frequency during NCP replication, resulting in SCV turnover. In summary, these
      data demonstrate that S. aureus phenotype switching occurs via a constitutive
      mechanism that generates a dynamic, antibiotic-resistant subpopulation of
      bacteria that can revert to the parental phenotype. The emergence of SCVs can
      therefore be considered a normal part of the S. aureus life cycle and provides an
      insurance policy against exposure to antibiotics that would otherwise eliminate
      the entire population.

PMID- 22865842
TI  - Function and regulation of isoforms of carbon monoxide dehydrogenase/acetyl
      coenzyme A synthase in Methanosarcina acetivorans.
AB  - Conversion of acetate to methane (aceticlastic methanogenesis) is an ecologically
      important process carried out exclusively by methanogenic archaea. An important
      enzyme for this process as well as for methanogenic growth on carbon monoxide is
      the five-subunit archaeal CO dehydrogenase/acetyl coenzyme A (CoA) synthase
      multienzyme complex (CODH/ACS) catalyzing both CO oxidation/CO(2) reduction and
      cleavage/synthesis of acetyl-CoA. Methanosarcina acetivorans C2A contains two
      very similar copies of a six-gene operon (cdh genes) encoding two isoforms of
      CODH/ACS (Cdh1 and Cdh2) and a single CdhA subunit, CdhA3. To address the role of
      the CODH/ACS system in M. acetivorans, mutational as well as promoter/reporter
      gene fusion analyses were conducted. Phenotypic characterization of cdh
      disruption mutants (three single and double mutants, as well as the triple
      mutant) revealed a strict requirement of either Cdh1 or Cdh2 for acetotrophic or
      carboxidotrophic growth, as well as for autotrophy, which demonstrated that both
      isoforms are bona fide CODH/ACS. While expression of the Cdh2-encoding genes was
      generally higher than that of genes encoding Cdh1, both appeared to be regulated
      differentially in response to growth phase and to changing substrate conditions.
      While dispensable for growth, CdhA3 clearly affected expression of cdh1,
      suggesting that it functions in signal perception and transduction rather than in
      catabolism. The data obtained argue for a functional hierarchy and regulatory
      cross talk of the CODH/ACS isoforms.

PMID- 22865843
TI  - Hal Is a Bacillus anthracis heme acquisition protein.
AB  - The metal iron is a limiting nutrient for bacteria during infection. Bacillus
      anthracis, the causative agent of anthrax and a potential weapon of bioterrorism,
      grows rapidly in mammalian hosts, which suggests that it efficiently attains iron
      during infection. Recent studies have uncovered both heme (isd) and siderophore
      mediated (asb) iron transport pathways in this pathogen. Whereas deletion of the
      asb genes results in reduced virulence, the loss of three surface components from
      isd had no effect, thereby leaving open the question of what additional factors
      in B. anthracis are responsible for iron uptake from the most abundant iron
      source for mammals, heme. Here, we describe the first functional characterization
      of bas0520, a gene recently implicated in anthrax disease progression. bas0520
      encodes a single near-iron transporter (NEAT) domain and several leucine-rich
      repeats. The NEAT domain binds heme, despite lacking a stabilizing tyrosine
      common to the NEAT superfamily of hemoproteins. The NEAT domain also binds
      hemoglobin and can acquire heme from hemoglobin in solution. Finally, deletion of
      bas0520 resulted in bacilli unable to grow efficiently on heme or hemoglobin as
      an iron source and yielded the most significant phenotype relative to that for
      other putative heme uptake systems, a result that suggests that this protein
      plays a prominent role in the replication of B. anthracis in hematogenous
      environments. Thus, we have assigned the name of Hal (heme-acquisition leucine
      rich repeat protein) to BAS0520. These studies advance our understanding of heme
      acquisition by this dangerous pathogen and justify efforts to determine the
      mechanistic function of this novel protein for vaccine or inhibitor development.

PMID- 22865844
TI  - Minor pilins of the type IV pilus system participate in the negative regulation
      of swarming motility.
AB  - Pseudomonas aeruginosa exhibits distinct surface-associated behaviors, including
      biofilm formation, flagellum-mediated swarming motility, and type IV pilus-driven
      twitching. Here, we report a role for the minor pilins, PilW and PilX, components
      of the type IV pilus assembly machinery, in the repression of swarming motility.
      Mutating either the pilW or pilX gene alleviates the inhibition of swarming
      motility observed for strains with elevated levels of the intracellular signaling
      molecule cyclic di-GMP (c-di-GMP) due to loss of BifA, a c-di-GMP-degrading
      phosphodiesterase. Blocking PilD peptidase-mediated processing of PilW and PilX
      renders the unprocessed proteins defective for pilus assembly but still
      functional in c-di-GMP-mediated swarming repression, indicating our ability to
      separate these functions. Strains with mutations in pilW or pilX also fail to
      exhibit the increase in c-di-GMP levels observed when wild-type (WT) or bifA
      mutant cells are grown on a surface. We also provide data showing that c-di-GMP
      levels are increased upon PilY1 overexpression in surface-grown cells and that
      this c-di-GMP increase does not occur in the absence of the SadC diguanylate
      cyclase. Increased levels of endogenous PilY1, PilX, and PilA are observed when
      cells are grown on a surface compared to liquid growth, linking surface growth
      and enhanced signaling via SadC. Our data support a model wherein PilW, PilX, and
      PilY1, in addition to their role(s) in type IV pilus biogenesis, function to
      repress swarming via modulation of intracellular c-di-GMP levels. By doing so,
      these pilus assembly proteins contribute to P. aeruginosa's ability to
      coordinately regulate biofilm formation with its two surface motility systems.

PMID- 22865845
TI  - Phosphoketolase pathway for xylose catabolism in Clostridium acetobutylicum
      revealed by 13C metabolic flux analysis.
AB  - Solvent-producing clostridia are capable of utilizing pentose sugars, including
      xylose and arabinose; however, little is known about how pentose sugars are
      catabolized through the metabolic pathways in clostridia. In this study, we
      identified the xylose catabolic pathways and quantified their fluxes in
      Clostridium acetobutylicum based on [1-(13)C]xylose labeling experiments. The
      phosphoketolase pathway was found to be active, which contributed up to 40% of
      the xylose catabolic flux in C. acetobutylicum. The split ratio of the
      phosphoketolase pathway to the pentose phosphate pathway was markedly increased
      when the xylose concentration in the culture medium was increased from 10 to 20 g
      liter(-1). To our knowledge, this is the first time that the in vivo activity of
      the phosphoketolase pathway in clostridia has been revealed. A phosphoketolase
      from C. acetobutylicum was purified and characterized, and its activity with
      xylulose-5-P was verified. The phosphoketolase was overexpressed in C.
      acetobutylicum, which resulted in slightly increased xylose consumption rates
      during the exponential growth phase and a high level of acetate accumulation.

PMID- 22865846
TI  - Biochemical characterization of pantoate kinase, a novel enzyme necessary for
      coenzyme A biosynthesis in the Archaea.
AB  - Although bacteria and eukaryotes share a pathway for coenzyme A (CoA)
      biosynthesis, we previously clarified that most archaea utilize a distinct
      pathway for the conversion of pantoate to 4'-phosphopantothenate. Whereas
      bacteria/eukaryotes use pantothenate synthetase and pantothenate kinase (PanK),
      the hyperthermophilic archaeon Thermococcus kodakarensis utilizes two novel
      enzymes: pantoate kinase (PoK) and phosphopantothenate synthetase (PPS). Here, we
      report a detailed biochemical examination of PoK from T. kodakarensis. Kinetic
      analyses revealed that the PoK reaction displayed Michaelis-Menten kinetics
      toward ATP, whereas substrate inhibition was observed with pantoate. PoK activity
      was not affected by the addition of CoA/acetyl-CoA. Interestingly, PoK displayed
      broad nucleotide specificity and utilized ATP, GTP, UTP, and CTP with comparable
      k(cat)/K(m) values. Sequence alignment of 27 PoK homologs revealed seven
      conserved residues with reactive side chains, and variant proteins were
      constructed for each residue. Activity was not detected when mutations were
      introduced to Ser104, Glu134, and Asp143, suggesting that these residues play
      vital roles in PoK catalysis. Kinetic analysis of the other variant proteins,
      with mutations S28A, H131A, R155A, and T186A, indicated that all four residues
      are involved in pantoate recognition and that Arg155 and Thr186 play important
      roles in PoK catalysis. Gel filtration analyses of the variant proteins indicated
      that Thr186 is also involved in dimer assembly. A sequence comparison between PoK
      and other members of the GHMP kinase family suggests that Ser104 and Glu134 are
      involved in binding with phosphate and Mg(2+), respectively, while Asp143 is the
      base responsible for proton abstraction from the pantoate hydroxy group.

PMID- 22865847
TI  - The AbrB2 autorepressor, expressed from an atypical promoter, represses the
      hydrogenase operon to regulate hydrogen production in Synechocystis strain
      PCC6803.
AB  - We have thoroughly investigated the abrB2 gene (sll0822) encoding an AbrB-like
      regulator in the wild-type strain of the model cyanobacterium Synechocystis
      strain PCC6803. We report that abrB2 is expressed from an active but atypical
      promoter that possesses an extended -10 element (TGTAATAT) that compensates for
      the absence of a -35 box. Strengthening the biological significance of these
      data, we found that the occurrence of an extended -10 promoter box and the
      absence of a -35 element are two well-conserved features in abrB2 genes from
      other cyanobacteria. We also show that AbrB2 is an autorepressor that is
      dispensable to cell growth under standard laboratory conditions. Furthermore, we
      demonstrate that AbrB2 also represses the hox operon, which encodes the Ni-Fe
      hydrogenase of biotechnological interest, and that the hox operon is weakly
      expressed even though it possesses the two sequences resembling canonical -10 and
      -35 promoter boxes. In both the AbrB2-repressed promoters of the abrB2 gene and
      the hox operon, we found a repeated DNA motif [TT-(N(5))-AAC], which could be
      involved in AbrB2 repression. Supporting this hypothesis, we found that a TT-to
      GG mutation of one of these elements increased the activity of the abrB2
      promoter. We think that our abrB2-deleted mutant with increased expression of the
      hox operon and hydrogenase activity, together with the reporter plasmids we
      constructed to analyze the abrB2 gene and the hox operon, will serve as useful
      tools to decipher the function and the regulation of hydrogen production in
      Synechocystis.

PMID- 22865848
TI  - Role of the Helicobacter pylori sensor kinase ArsS in protein trafficking and
      acid acclimation.
AB  - Helicobacter pylori survives and grows at low pHs via acid acclimation mechanisms
      that enable periplasmic pH homeostasis. Important components include a
      cytoplasmic urease; a pH-gated urea channel, UreI; and periplasmic alpha-carbonic
      anhydrase. To allow the rapid adjustment of periplasmic pH, acid acclimation
      components are recruited to the inner membrane in acid. The ArsRS two-component
      system, in an acid-responsive manner, controls the transcription of the urease
      gene cluster and alpha-carbonic anhydrase. The aim of this study is to determine
      the role of ArsS in protein trafficking as a component of acid acclimation. H.
      pylori wild-type and DeltaarsS bacteria were incubated at acidic and neutral pHs.
      Intact bacteria, purified membranes, and total protein were analyzed by Western
      blotting and urease activity measurements. The total urease activity level was
      decreased in the DeltaarsS strain, but the acid activation of UreI was
      unaffected. A 30-min acid exposure increased the level and activity of urease
      proteins at the membrane in the wild type but not in the DeltaarsS strain. The
      urease levels and activity of the DeltaarsS strain after a 90-min acid exposure
      were similar to those of the wild type. ArsS, in addition to its role in urease
      gene transcription, is also involved in the recruitment of urease proteins to the
      inner membrane to augment acid acclimation during acute acid exposure. Urease
      membrane recruitment following prolonged acid exposure in the absence of ArsS was
      similar to that of the wild type, suggesting a compensatory mechanism, possibly
      regulated by FlgS, underscoring the importance of urease membrane recruitment and
      activation in periplasmic pH homeostasis.

PMID- 22865849
TI  - Reduced Na+ affinity increases turnover of Salmonella enterica serovar
      Typhimurium MelB.
AB  - The melibiose permease of Salmonella enterica serovar Typhimurium (MelB(St))
      catalyzes symport of melibiose with Na(+), Li(+), or H(+). Bioinformatics and
      mutational analyses indicate that a conserved Gly117 (helix IV) is a component of
      the Na(+)-binding site. In this study, Gly117 was mutated to Ser, Asn, or Cys.
      All three mutations increase the maximum rate (V(max)) for melibiose transport in
      Escherichia coli DW2 and greatly decrease Na(+) affinity, indicating that
      intracellular release of Na(+) is facilitated. Rapid melibiose transport,
      particularly by the G117N mutant, triggers osmotic lysis in the lag phase of
      growth. The findings support the previous conclusion that Gly117 plays an
      important role in cation binding and translocation. Furthermore, a spontaneous
      second-site mutation (P148L between loop(4-5) and helix V) in the G117C mutant
      prevents cell lysis. This mutation significantly decreases V(max) with little
      effect on cosubstrate binding in G117C, G117S, and G117N mutants. Thus, the P148L
      mutation specifically inhibits transport velocity and thereby blocks the lethal
      effect of elevated melibiose transport in the Gly117 mutants.

PMID- 22865850
TI  - Role of genetic redundancy in polyhydroxyalkanoate (PHA) polymerases in PHA
      biosynthesis in Rhodospirillum rubrum.
AB  - This study investigated the apparent genetic redundancy in the biosynthesis of
      polyhydroxyalkanoates (PHAs) in the Rhodospirillum rubrum genome revealed by the
      occurrence of three homologous PHA polymerase genes (phaC1, phaC2, and phaC3). In
      vitro biochemical assays established that each gene product encodes PHA
      polymerase. A series of single, double, and triple phaC deletion mutants were
      characterized with respect to PHA production and growth capabilities on acetate
      or hexanoate as the sole carbon source. These analyses establish that phaC2
      contributes the major capacity to produce PHA, even though the PhaC2 protein is
      not the most efficient PHA polymerase biocatalyst. In contrast, phaC3 is an
      insignificant contributor to PHA productivity, and phaC1, the PHA polymerase
      situated in the PHA biosynthetic operon, plays a minor role in this capability,
      even though both of these genes encode PHA polymerases that are more efficient
      enzymes. These observations are consistent with the finding that PhaC1 and PhaC3
      occur at undetectable levels, at least 10-fold lower than that of PhaC2. The
      monomers in the PHA polymer produced by these strains establish that PhaC2 is
      responsible for the incorporation of the C(5) and C(6) monomers. The in vitro
      characterizations indicate that heteromeric PHA polymerases composed of mixtures
      of different PhaC paralogs are more efficient catalysts, suggesting that these
      proteins form complexes. Finally, the physiological role of PHA accumulation in
      enhancing the fitness of R. rubrum was indicated by the relationship between PHA
      content and growth capabilities of the genetically manipulated strains that
      express different levels of the PHA polymer.

PMID- 22865851
TI  - Genome-wide responses of the model archaeon Halobacterium sp. strain NRC-1 to
      oxygen limitation.
AB  - As part of a comprehensive postgenomic investigation of the model archaeon
      Halobacterium sp. strain NRC-1, we used whole-genome DNA microarrays to compare
      transcriptional profiles of cells grown under anaerobic or aerobic conditions.
      When anaerobic growth supported by arginine fermentation was compared to aerobic
      growth, genes for arginine fermentation (arc) and anaerobic respiration (dms),
      using trimethylamine N-oxide (TMAO) as the terminal electron acceptor, were
      highly upregulated, as was the bop gene, required for phototrophic growth. When
      arginine fermentation was compared to anaerobic respiration with TMAO, the arc
      and dms genes were both induced with arginine, while TMAO induced the bop gene
      and major gas vesicle protein (gvpAC) genes specifying buoyant gas vesicles.
      Anaerobic conditions with either TMAO or arginine also upregulated the cba genes,
      encoding one of three cytochrome oxidases. In-frame deletion of two COG3413
      family regulatory genes, bat and dmsR, showed downregulation of the bop gene
      cluster and loss of purple membrane synthesis and downregulation of the dms
      operon and loss of anaerobic respiration capability, respectively. Bioinformatic
      analysis identified additional regulatory and sensor genes that are likely
      involved in the full range of cellular responses to oxygen limitation. Our
      results show that the Halobacterium sp. has evolved a carefully orchestrated set
      of responses to oxygen limitation. As conditions become more reducing, cells
      progressively increase buoyancy, as well as capabilities for phototrophy,
      scavenging of molecular oxygen, anaerobic respiration, and fermentation.

PMID- 22865852
TI  - Battling big booze and big bet: why we should not accept direct funding from the
      alcohol or gambling industries.

PMID- 22865853
TI  - Hyaluronan anchored to activated CD44 on central nervous system vascular
      endothelial cells promotes lymphocyte extravasation in experimental autoimmune
      encephalomyelitis.
AB  - The extravasation of lymphocytes across central nervous system (CNS) vascular
      endothelium is a key step in inflammatory demyelinating diseases including
      multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The
      glycosaminoglycan hyaluronan (HA) and its receptor, CD44, have been implicated in
      this process but their precise roles are unclear. We find that CD44(-/-) mice
      have a delayed onset of EAE compared with wild type animals. Using an in vitro
      lymphocyte rolling assay, we find that fewer slow rolling (<1 MUm/s) wild type
      (WT) activated lymphocytes interact with CD44(-/-) brain vascular endothelial
      cells (ECs) than with WT ECs. We also find that CD44(-/-) ECs fail to anchor HA
      to their surfaces, and that slow rolling lymphocyte interactions with WT ECs are
      inhibited when the ECs are treated with a pegylated form of the PH20
      hyaluronidase (PEG-PH20). Subcutaneous injection of PEG-PH20 delays the onset of
      EAE symptoms by ~1 day and transiently ameliorates symptoms for 2 days following
      disease onset. These improved symptoms correspond histologically to degradation
      of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired
      CD4(+) T-cell extravasation. Collectively these data suggest that HA tethered to
      CD44 on CNS ECs is critical for the extravasation of activated T cells into the
      CNS providing new insight into the mechanisms promoting inflammatory
      demyelinating disease.

PMID- 22865854
TI  - Targeted protein engineering provides insights into binding mechanism and
      affinities of bacterial collagen adhesins.
AB  - The collagen-binding bacterial proteins, Ace and Cna, are well characterized on
      the biochemical and structural level. Despite overall structural similarity,
      recombinant forms of the Ace and Cna ligand-binding domains exhibit significantly
      different affinities and binding kinetics for collagen type I (CI) in vitro. In
      this study, we sought to understand, in submolecular detail, the bases for these
      differences. Using a structure-based approach, we engineered Cna and Ace variants
      by altering specific structural elements within the ligand-binding domains.
      Surface plasmon resonance-based binding analysis demonstrated that mutations that
      are predicted to alter the orientation of the Ace and Cna N(1) and N(2)
      subdomains significantly affect the interaction between the MSCRAMM (microbial
      surface components recognizing adhesive matrix molecule) and CI in vitro,
      including affinity, association/dissociation rates and binding ratio. Moreover,
      we utilized this information to engineer an Ace variant with an 11,000-fold
      higher CI affinity than the parent protein. Finally, we noted that several
      engineered proteins that exhibited a weak interaction with CI recognized more
      sites on CI, suggesting an inverse correlation between affinity and specificity.

PMID- 22865855
TI  - Extracellular matrix lumican promotes bacterial phagocytosis, and Lum-/- mice
      show increased Pseudomonas aeruginosa lung infection severity.
AB  - Phagocytosis is central to bacterial clearance, but the exact mechanism is
      incompletely understood. Here, we show a novel and critical role for lumican, the
      connective tissue extracellular matrix small leucine-rich repeat proteoglycan, in
      CD14-mediated bacterial phagocytosis. In Psuedomonas aeruginosa lung infections,
      lumican-deficient (Lum(-/-)) mice failed to clear the bacterium from lungs,
      tissues, and showed a dramatic increase in mortality. In vitro, phagocytosis of
      nonopsonized gram-negative Escherichia coli and P. aeruginosa was inhibited in
      Lum(-/-) peritoneal macrophages (MPhis). Lumican co-localized with CD14, CD18,
      and bacteria on Lum(+/+) MPhi surfaces. Using two different P. aeruginosa strains
      that require host CD14 (808) or CD18/CR3 (P1) for phagocytosis, we showed that
      lumican has a larger role in CD14-mediated phagocytosis. Recombinant lumican
      (rLum) restored phagocytosis in Lum(-/-) MPhis. Surface plasmon resonance showed
      specific binding of rLum to CD14 (K(A) = 2.15 * 10(6) M(-1)), whereas rLumY20A,
      and not rLumY21A, where a tyrosine in each was replaced with an alanine, showed
      60-fold decreased binding. The rLumY20A variant also failed to restore
      phagocytosis in Lum(-/-) MPhis, indicating Tyr-20 to be functionally important.
      Thus, in addition to a structural role in connective tissues, lumican has a major
      protective role in gram-negative bacterial infections, a novel function for small
      leucine-rich repeat proteoglycans.

PMID- 22865856
TI  - An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell
      cell fusion.
AB  - Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs)
      form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we
      reported that two seven-transmembrane molecules, osteoclast stimulatory
      transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane
      protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in
      vivo and in vitro. However, signaling required to regulate FBGC fusion remained
      largely unknown. Here, we show that signal transducer and activator of
      transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and
      elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1
      activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and
      DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co
      expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of
      FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and
      DC-STAMP expression and governs fusogenic mechanisms in FBGCs.

PMID- 22865857
TI  - CD8 lineage-specific regulation of interleukin-7 receptor expression by the
      transcriptional repressor Gfi1.
AB  - Interleukin-7 receptor alpha (IL-7Ralpha) is essential for T cell survival and
      differentiation. Glucocorticoids are potent enhancers of IL-7Ralpha expression
      with diverse roles in T cell biology. Here we identify the transcriptional
      repressor, growth factor independent-1 (Gfi1), as a novel intermediary in
      glucocorticoid-induced IL-7Ralpha up-regulation. We found Gfi1 to be a major
      inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T
      hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly
      blunted IL-7Ralpha up-regulation by dexamethasone. To further assess the role of
      Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice,
      in which a modified Il7r locus expresses GFP to report Il7r gene transcription.
      By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1
      transgenic mice, we document in vivo that IL-7Ralpha transcription is up
      regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed.
      Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8(+), and not
      CD4(+) T cells or immature thymocytes. These results identify Gfi1 as a specific
      transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.

PMID- 22865858
TI  - Multiplexed activity-based protein profiling of the human pathogen Aspergillus
      fumigatus reveals large functional changes upon exposure to human serum.
AB  - Environmental adaptability is critical for survival of the fungal human pathogen
      Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that
      exposure of the fungal pathogen to human serum would lead to significant
      alterations to the organism's physiology, including metabolic activity and stress
      response. Shifts in functional pathway and corresponding enzyme reactivity of A.
      fumigatus upon exposure to the human host may represent much needed prognostic
      indicators of fungal infection. To address this, we employed a multiplexed
      activity-based protein profiling (ABPP) approach coupled to quantitative mass
      spectrometry-based proteomics to measure broad enzyme reactivity of the fungus
      cultured with and without human serum. ABPP showed a shift from aerobic
      respiration to ethanol fermentation and utilization over time in the presence of
      human serum, which was not observed in serum-free culture. Our approach provides
      direct insight into this pathogen's ability to survive, adapt, and proliferate.
      Additionally, our multiplexed ABPP approach captured a broad swath of enzyme
      reactivity and functional pathways and provides a method for rapid assessment of
      the A. fumigatus response to external stimuli.

PMID- 22865859
TI  - GATA2 is a critical transactivator for the human IL1RL1/ST2 promoter in mast
      cells/basophils: opposing roles for GATA2 and GATA1 in human IL1RL1/ST2 gene
      expression.
AB  - The IL1RL1/ST2 gene encodes a receptor for IL-33. Signaling from IL1RL1/ST2
      induced by IL-33 binding was recently identified as a modulator of the Th2
      response. The target cells for IL-33 are restricted in some hematopoietic
      lineages, including mast cells, basophils, eosinophils, Th2 cells, natural killer
      cells, and dendritic cells. To clarify the molecular mechanisms of cell type
      specific IL1RL1/ST2 expression in mast cells and basophils, transcriptional
      regulation of the human IL1RL1/ST2 promoter was investigated using the mast cell
      line LAD2 and the basophilic cell line KU812. Reporter assays suggested that two
      GATA motifs just upstream of the transcription start site in the ST2 promoter are
      critical for transcriptional activity. These two GATA motifs possess the capacity
      to bind GATA1 and GATA2 in EMSA. ChIP assay showed that GATA2, but not GATA1,
      bound to the ST2 promoter in LAD2 cells and that histone H3 at the ST2 promoter
      was acetylated in LAD2 cells, whereas binding of GATA1 and GATA2 to the ST2
      promoter was detected in KU812 cells. Knockdown of GATA2 mRNA by siRNA reduced
      ST2 mRNA levels in KU812 and LAD2 cells and ST2 protein levels in LAD2 cells; in
      contrast, GATA1 siRNA transfection up-regulated ST2 mRNA levels in KU812 cells.
      The ST2 promoter was transactivated by GATA2 and repressed by GATA1 in
      coexpression analysis. When these siRNAs were introduced into human peripheral
      blood basophils, GATA2 siRNA reduced ST2 mRNA, whereas GATA1 siRNA up-regulated
      ST2 mRNA. These results indicate that GATA2 and GATA1 positively and negatively
      control human ST2 gene transcription, respectively.

PMID- 22865860
TI  - Identification and characterization of an extramitochondrial human 3-hydroxy-3
      methylglutaryl-CoA lyase.
AB  - 3-Hydroxy-3-methylglutaryl-CoA lyase-like protein (HMGCLL1) has been annotated in
      the Mammalian Genome Collection as a previously unidentified human HMG-CoA lyase
      (HMGCL). To test the validity of this annotation and evaluate the physiological
      role of the protein, plasmids were constructed for protein expression in
      Escherichia coli and Pichia pastoris. Protein expression in E. coli produced
      insoluble material. In contrast, active HMGCLL1 could be recovered upon
      expression in P. pastoris. Antibodies were prepared against a unique peptide
      sequence found in the N terminus of the protein. In immunodetection experiments,
      the antibodies discriminated between HMGCLL1 and mitochondrial HMGCL. Purified
      enzyme was characterized and demonstrated to cleave HMG-CoA to acetoacetate and
      acetyl-CoA with catalytic and affinity properties comparable with human
      mitochondrial HMGCL. The deduced HMGCLL1 sequence contains an N-terminal
      myristoylation motif; the putative modification site was eliminated by
      construction of a G2A HMGCLL1. Modification of both proteins was attempted using
      human N-myristoyltransferase and [(3)H]myristoyl-CoA. Wild-type protein was
      clearly modified, whereas G2A protein was not labeled. Myristoylation of HMGCLL1
      affects its cellular localization. Upon transfection of appropriate expression
      plasmids into COS1 cells, immunofluorescence detection indicates that G2A HMGCLL1
      exhibits a diffuse pattern, suggesting a cytosolic location. In contrast, wild
      type HMGCLL1 exhibits a punctate as well as a perinuclear immunostaining pattern,
      indicating myristoylation dependent association with nonmitochondrial membrane
      compartments. In control experiments with the HMGCL expression plasmid, protein
      is localized in the mitochondria, as anticipated. The available results for COS1
      cell expression, as well as endogenous expression in U87 cells, indicate that
      HMGCLL1 is an extramitochondrial hydroxymethylglutaryl-CoA lyase.

PMID- 22865861
TI  - Proteolytic processing regulates Toll-like receptor 3 stability and endosomal
      localization.
AB  - Toll-like receptors (TLRs) 3, 7, and 9 are innate immune receptors that recognize
      nucleic acids from pathogens in endosomes and initiate signaling transductions
      that lead to cytokine production. Activation of TLR9 for signaling requires
      proteolytic processing within the ectodomain by endosome-associated proteases.
      Whether TLR3 requires similar proteolytic processing to become competent for
      signaling remains unclear. Herein we report that human TLR3 is proteolytically
      processed to form two fragments in endosomes. Unc93b1 is required for processing
      by transporting TLR3 through the Golgi complex and to the endosomes. Proteolytic
      cleavage requires the eight-amino acid Loop1 within leucine-rich repeat 12 of the
      TLR3 ectodomain. Proteolytic cleavage is not required for TLR3 signaling in
      response to poly(I:C), although processing could modulate the degree of response
      toward viral double-stranded RNAs, especially in mouse cells. Both the full
      length and cleaved fragments of TLR3 can bind poly(I:C) and are present in
      endosomes. However, although the full-length TLR3 has a half-life in HEK293T
      cells of 3 h, the cleaved fragments have half-lives in excess of 7 h. Inhibition
      of TLR3 cleavage by either treatment with cathepsin inhibitor or by a mutation in
      Loop1 decreased the abundance of TLR3 in endosomes targeted for lysosomal
      degradation.

PMID- 22865862
TI  - Protein kinase A-mediated phosphorylation of Pah1p phosphatidate phosphatase
      functions in conjunction with the Pho85p-Pho80p and Cdc28p-cyclin B kinases to
      regulate lipid synthesis in yeast.
AB  - Pah1p, which functions as phosphatidate phosphatase (PAP) in the yeast
      Saccharomyces cerevisiae, plays a crucial role in lipid homeostasis by
      controlling the relative proportions of its substrate phosphatidate and its
      product diacylglycerol. The diacylglycerol produced by PAP is used for the
      synthesis of triacylglycerol as well as for the synthesis of phospholipids via
      the Kennedy pathway. Pah1p is a highly phosphorylated protein in vivo and has
      been previously shown to be phosphorylated by the protein kinases Pho85p-Pho80p
      and Cdc28p-cyclin B. In this work, we showed that Pah1p was a bona fide substrate
      for protein kinase A, and we identified by mass spectrometry and mutagenesis that
      Ser-10, Ser-677, Ser-773, Ser-774, and Ser-788 were the target sites of
      phosphorylation. Protein kinase A-mediated phosphorylation of Pah1p inhibited its
      PAP activity by decreasing catalytic efficiency, and the inhibitory effect was
      primarily conferred by phosphorylation at Ser-10. Analysis of the S10A and S10D
      mutations (mimicking dephosphorylation and phosphorylation, respectively), alone
      or in combination with the seven alanine (7A) mutations of the sites
      phosphorylated by Pho85p-Pho80p and Cdc28p-cyclin B, indicated that
      phosphorylation at Ser-10 stabilized Pah1p abundance and inhibited its
      association with membranes, PAP activity, and triacylglycerol synthesis. The S10A
      mutation enhanced the physiological effects imparted by the 7A mutations, whereas
      the S10D mutations attenuated the effects of the 7A mutations. These data
      indicated that the protein kinase A-mediated phosphorylation of Ser-10 functions
      in conjunction with the phosphorylations mediated by Pho85p-Pho80p and Cdc28p
      cyclin B and that phospho-Ser-10 should be dephosphorylated for proper PAP
      function.

PMID- 22865863
TI  - The calcium/calcineurin pathway promotes hemidesmosome stability through
      inhibition of beta4 integrin phosphorylation.
AB  - Cell migration depends on cells being able to create and disassemble adhesive
      contacts. Hemidesmosomes are multiprotein structures that attach epithelia to
      basal lamina and disassemble during migration and carcinoma invasion.
      Phosphorylation of the beta4 integrin, a hemidesmosome component, induces
      disassembly. Although kinases involved in beta4 phosphorylation have been
      identified, little is known about phosphatases countering kinase action. Here we
      report that calcineurin, a serine-threonine protein phosphatase, regulates beta4
      phosphorylation. Calcineurin inhibitor cyclosporin A (CsA) and calcineurin-siRNA
      increase beta4 phosphorylation, induce hemidesmosome disassembly, and increase
      migration in HaCat keratinocytes, suggesting that calcineurin negatively
      regulates beta4 phosphorylation. We found no direct dephosphorylation of beta4 by
      calcineurin or association between beta4 and calcineurin, suggesting indirect
      regulation of beta4 phosphorylation. We therefore assessed calcineurin influence
      on MAPK and PKC, known to phosphorylate beta4. CsA increased MAPK activity,
      whereas MAPK inhibitors reduced CsA-induced beta4 phosphorylation, suggesting
      that calcineurin restricts beta4 phosphorylation by MAPK. Calcineurin is
      activated by calcium. Increased [Ca(2+)](i) reduces beta4 phosphorylation and
      stabilizes hemidesmosomes, effects that are reversed by CsA, indicating that
      calcineurin mediates calcium effects on beta4. However, MAPK activation is
      increased when [Ca(2+)](i) is increased, suggesting that calcineurin activates an
      additional mechanism that counteracts MAPK-induced beta4 phosphorylation.
      Interestingly, in some squamous cell carcinoma cells, which have reduced
      hemidesmosomes and increased beta4 phosphorylation, an increase in [Ca(2+)](i)
      using thapsigargin, bradykinin, or acetylcholine can increase hemidesmosomes and
      reduce beta4 phosphorylation in a calcineurin-dependent manner. These findings
      have implications in calcineurin-inhibitor induced carcinoma, a complication of
      immunosuppressive therapy.

PMID- 22865864
TI  - Ventricular tachycardia following right ventricular disconnection for
      arrhythmogenic right ventricular cardiomyopathy.

PMID- 22865865
TI  - Relative apical sparing of longitudinal strain using two-dimensional speckle
      tracking echocardiography is both sensitive and specific for the diagnosis of
      cardiac amyloidosis.
AB  - BACKGROUND: The diagnosis of cardiac amyloidosis (CA) is challenging owing to
      vague symptomatology and non-specific echocardiographic findings. OBJECTIVE: To
      describe regional patterns in longitudinal strain (LS) using two-dimensional
      speckle-tracking echocardiography in CA and to test the hypothesis that regional
      differences would help differentiate CA from other causes of increased left
      ventricular (LV) wall thickness. METHODS AND RESULTS: 55 consecutive patients
      with CA were compared with 30 control patients with LV hypertrophy (n=15 with
      hypertrophic cardiomyopathy, n=15 with aortic stenosis). A relative apical LS of
      1.0, defined using the equation (average apical LS/(average basal LS + mid-LS)),
      was sensitive (93%) and specific (82%) in differentiating CA from controls (area
      under the curve 0.94). In a logistic regression multivariate analysis, relative
      apical LS was the only parameter predictive of CA (p=0.004). CONCLUSIONS: CA is
      characterised by regional variations in LS from base to apex. A relative 'apical
      sparing' pattern of LS is an easily recognisable, accurate and reproducible
      method of differentiating CA from other causes of LV hypertrophy.

PMID- 22865866
TI  - Scientific letter: A double-blind, randomised, placebo-controlled, 3-month
      crossover trial of night-time oxygen therapy in advanced systolic heart failure.

PMID- 22865867
TI  - Cost-effectiveness of presentation versus delayed troponin testing for acute
      myocardial infarction.
AB  - OBJECTIVES: To estimate the cost-effectiveness of delayed troponin testing for
      myocardial infarction compared with troponin testing at presentation. DESIGN:
      Decision analysis modelling of cost-effectiveness using secondary data sources.
      SETTING: Acute hospitals in the UK. POPULATION: Patients attending hospital with
      suspected myocardial infarction but a normal or non-diagnostic ECG and no major
      comorbidities requiring admission. INTERVENTIONS: Delayed troponin testing (10 h
      after symptom onset) compared with standard and high-sensitivity troponin testing
      at presentation and no testing. Sensitivity analysis evaluated high-sensitivity
      troponin testing 3 h after initial assessment. MAIN OUTCOME MEASURES: The
      incremental cost per quality-adjusted life year (QALY) gained by each strategy,
      compared with the next most effective alternative, and the probability of each
      strategy being cost-effective at varying willingness-to-pay per QALY gained.
      RESULTS: In all scenarios tested, presentation high-sensitivity troponin testing
      was the most effective strategy with an incremental cost-effectiveness ratio
      below the L20 000/QALY threshold. 10 h troponin testing was only likely to be
      cost-effective if a discharge decision could be made as soon as a negative result
      was available and the L30 000/QALY threshold was used, or if a lower sensitivity
      estimate for presentation high-sensitivity troponin was assumed. Sensitivity
      analysis showed that including high-sensitivity troponin testing at presentation
      and 3 h in the analysis makes this the most cost-effective strategy. CONCLUSIONS:
      Delayed troponin testing is unlikely to be cost-effective compared with high
      sensitivity troponin testing at presentation in most scenarios. Current NICE
      chest pain guidelines do not promote cost-effective care.

PMID- 22865868
TI  - Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal
      pro B-type natriuretic peptide in the diagnosis of patients with atrial
      fibrillation and dyspnoea.
AB  - OBJECTIVES: Due to different release mechanisms, mid-regional pro-atrial
      natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type
      natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in
      patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for
      their diagnostic value in patients with AF and sinus rhythm (SR). DESIGN:
      Prospective cohort study. SETTING: University hospital, emergency department.
      PATIENTS: 632 consecutive patients presenting with acute dyspnoea. MAIN OUTCOME
      MEASURES: MR proANP and NT proBNP plasma levels were determined. The diagnosis of
      AHF was adjudicated by two independent cardiologists using all available data.
      Patients received long-term follow-up. RESULTS: AF was present in 151 patients
      (24%). MR proANP and NT proBNP levels were significantly higher in the AF group
      compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR
      proANP, p<0.001 and 4916 (2169-10285) versus 1177 (258-5166) pg/ml, p<0.001 for
      NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90,
      95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off
      levels in AF patients were significantly higher compared with the optimal cut-off
      levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500
      pg/ml respectively). After adjustment in multivariable Cox proportional hazard
      analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13
      (1.09-1.17), per 100 pmol/l increase, p<0.001). CONCLUSION: In AF patients, NT
      proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The
      rhythm at presentation has to be taken into account because plasma levels of both
      peptides are significantly higher in patients with AF compared with SR.

PMID- 22865869
TI  - 'FIT FOR PURPOSE'. The COACH program improves lifestyle and biomedical cardiac
      risk factors.

PMID- 22865870
TI  - Fluoroquinolones and the risk of serious arrhythmia: a population-based study.
AB  - BACKGROUND: Fluoroquinolones have been suspected to cause cardiac arrhythmia but
      data are lacking, particularly for the individual fluoroquinolones. We assessed
      the risk of serious arrhythmia, defined as ventricular arrhythmia or
      sudden/unattended death identified in hospital discharge diagnoses, related to
      fluoroquinolones as a class as well as for each individual molecule. METHODS: We
      used a cohort of patients treated for respiratory conditions from 1 January 1990
      to 31 December 2005, identified using the healthcare databases from the province
      of Quebec (Canada), with follow-up until 31 March 2007. A nested case-control
      analysis was performed within this cohort, with all cases of serious arrhythmia
      occurring during follow-up identified from hospitalization records. These cases
      were matched with up to 20 controls. Conditional logistic regression was used to
      compute adjusted rate ratios (RRs) of serious arrhythmia associated with
      fluoroquinolone use. RESULTS: Within the cohort of 605127 subjects, 1838 cases
      were identified (incidence rate=4.7/10000 person-years). The rate of serious
      arrhythmia was elevated with current fluoroquinolone use (RR=1.76; 95% confidence
      interval [CI], 1.19-2.59), in particular with new current use (RR=2.23; 95% CI,
      1.31-3.80). Gatifloxacin use was associated with the highest rate (RR=7.38; 95%
      CI, 2.30-23.70); moxifloxacin and ciprofloxacin were also associated with
      elevated rates of serious arrhythmia (RR=3.30; 95% CI, 1.47-7.37 and RR=2.15; 95%
      CI, 1.34-3.46, respectively). CONCLUSIONS: The use fluoroquinolones is associated
      with an elevated risk of serious arrhythmia, with some differences among
      molecules. Given that the individual fluoroquinolones share various indications,
      the relative risks of serious arrhythmia could inform the choice of different
      molecules in high-risk patients.

PMID- 22865871
TI  - Effects of short-course oral corticosteroid therapy in early dengue infection in
      Vietnamese patients: a randomized, placebo-controlled trial.
AB  - BACKGROUND: Patients with dengue can experience a variety of serious
      complications including hypovolemic shock, thrombocytopenia, and bleeding. These
      problems occur as plasma viremia is resolving and are thought to be
      immunologically mediated. Early corticosteroid therapy may prevent the
      development of such complications but could also prolong viral clearance.
      METHODS: We performed a randomized, placebo-controlled, blinded trial of low-dose
      (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in
      Vietnamese patients aged 5-20 years admitted with dengue and fever for <=72
      hours, aiming to assess potential harms from steroid use during the viremic
      phase. Intention-to-treat analysis was performed using linear trend tests with a
      range of clinical and virological endpoints specified in advance. In addition to
      recognized complications of dengue, we focused on the are under the curve for
      serial plasma viremia measurements and the number of days after enrollment to
      negative viremia and dengue nonstructural protein 1 status. RESULTS: Between
      August 2009 and January 2011, 225 participants were randomized to 1 of the 3
      treatment arms. Baseline characteristics were similar across the groups. All
      patients recovered fully and adverse events were infrequent. Aside from a trend
      toward hyperglycemia in the steroid recipients, we found no association between
      treatment allocation and any of the predefined clinical, hematological, or
      virological endpoints. CONCLUSIONS: Use of oral prednisolone during the early
      acute phase of dengue infection was not associated with prolongation of viremia
      or other adverse effects. Although not powered to assess efficacy, we found no
      reduction in the development of shock or other recognized complications of dengue
      virus infection in this study.

PMID- 22865872
TI  - Mycobacterium tuberculosis Beijing strains favor transmission but not drug
      resistance in China.
AB  - BACKGROUND: The Mycobacterium tuberculosis Beijing strains are widespread
      globally. We aimed to determine whether Beijing strains in China are more likely
      than other strains to spread, and whether they are more likely to become drug
      resistant. We also sought to determine whether different Beijing sublineages have
      distinct phenotypic characteristics. METHODS: We conducted a population-based
      molecular epidemiologic study in 6 provinces in China from 2009 to 2010. We
      analyzed data and specimens from culture-confirmed pulmonary tuberculosis
      patients. Each patient's isolate was genotyped using 16-loci variable number of
      tandem repeats and 6 single-nucleotide polymorphisms. RESULTS: By genotyping,
      75.0% (1031/1375) of the strains of M. tuberculosis were Beijing strains. Beijing
      strains were more likely than non-Beijing strains to be in a genotypic cluster
      (odds ratio, 2.40, P < .001), and were significantly associated with younger age
      (P(trend) < .05). There was no significant difference in the proportion of
      Beijing strains and non-Beijing strains that were drug resistant, even when
      stratified by new vs retreatment patients. We identified 6 sublineages of Beijing
      strains in the study population. The modern sublineage of Beijing strains were
      more likely than the ancient sublineages to be clustered (odds ratio, 2.27, P <
      .001). CONCLUSIONS: Beijing strains of M. tuberculosis were significantly
      associated with genotypic clustering, reflecting recent transmission, and younger
      age, but were not associated with drug resistance. Future studies of Beijing
      family strains should avoid assuming and attributing characteristics to the
      entire family and should assess strains of specific sublineages and/or settings.

PMID- 22865873
TI  - Editorial commentary. Short-course oral corticosteroid therapy is not effective
      in early dengue infection.

PMID- 22865874
TI  - Loss of Maged1 results in obesity, deficits of social interactions, impaired
      sexual behavior and severe alteration of mature oxytocin production in the
      hypothalamus.
AB  - MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of
      these genes have been involved in Prader-Willi syndrome (PWS), which includes
      hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here,
      we show that Maged1-deficient mice develop progressive obesity associated with
      hyperphagia and reduced motor activity. Loss of Maged1 also results in a complex
      behavioral syndrome that includes reduced social interactions and memory,
      deficient sexual behavior, as well as increased anxiety and self-grooming.
      Oxytocin (OT), which is produced in the hypothalamus, can act as a
      neurotransmitter that reduces anxiety, promotes social behaviors and regulates
      food intake. Growing evidences indicate that OT is involved in autism. We found
      that Maged1 mutants showed a severe reduction in the levels of mature OT, but not
      of its precursors, in the hypothalamus. Moreover, the administration of OT
      rescued the deficit in social memory of these mice. We conclude that Maged1 is
      required for OT processing or stability. A decrease in mature OT levels in Maged1
      mutants affects social interactions and possibly other behavioral processes. Our
      observations suggest that, in human, MAGED1 could play a role in autism or cause
      a neurodevelopmental condition that is reminiscent of the PWS.

PMID- 22865875
TI  - Alzheimer's disease in a dish: promises and challenges of human stem cell models.
AB  - Human pluripotent stem cells can differentiate into disease-relevant cell types,
      which capture the unique genome of an individual patient and provide insight into
      pathological mechanisms of human disease. Recently, human stem cell models for
      Alzheimer's disease (AD), the most common neurodegenerative dementia, have been
      described. Stem cell-derived neurons from patients with familial and sporadic AD
      and Down's syndrome recapitulate human disease phenotypes such as amyloid beta
      peptide production, hyperphosphorylation of tau protein and endosomal
      abnormalities. Treatment of human neurons with small molecules can modulate these
      phenotypes, demonstrating the utility of this system for drug development and
      screening. This review will highlight the current AD stem cell models and discuss
      the remaining challenges and potential future directions of this field.

PMID- 22865876
TI  - Measurement of S-nitrosylation occupancy in the myocardium with cysteine-reactive
      tandem mass tags: short communication.
AB  - RATIONALE: S-nitrosylation (SNO) is a reversible, thiol-based protein
      modification that plays an important role in the myocardium by protecting
      critical cysteine residues from oxidation. However, little is known with regard
      to the percentage of a given protein that is modified by SNO (ie, SNO occupancy).
      Current methods allow for the relative quantification of SNO levels, but not for
      the determination of SNO occupancy. OBJECTIVE: To develop a method for the
      measurement of SNO occupancy, and apply this methodology to determine SNO
      occupancy in the myocardium. METHODS AND RESULTS: We developed a differential
      cysteinereactive tandem mass tag (cysTMT) labeling procedure for the measurement
      of SNO occupancy. To validate this cysTMT labeling method, we treated whole-heart
      homogenates with the S-nitrosylating agent S-nitrosoglutathione and determined
      maximal SNO occupancy. We also examined SNO occupancy under more physiological
      conditions and observed that SNO occupancy is low for most protein targets at
      baseline. Following ischemic preconditioning, SNO occupancy increased to an
      intermediate level compared to baseline and Snitrosoglutathione treatment, and
      this is consistent with the ability of SNO to protect against cysteine oxidation.
      CONCLUSIONS: This novel cysTMT labeling approach provides a method for examining
      SNO occupancy in the myocardium. Using this approach, we demonstrated that IPC
      induced SNO occupancy levels are sufficient to protect against oxidation.

PMID- 22865877
TI  - COPT6 is a plasma membrane transporter that functions in copper homeostasis in
      Arabidopsis and is a novel target of SQUAMOSA promoter-binding protein-like 7.
AB  - Among the mechanisms controlling copper homeostasis in plants is the regulation
      of its uptake and tissue partitioning. Here we characterized a newly identified
      member of the conserved CTR/COPT family of copper transporters in Arabidopsis
      thaliana, COPT6. We showed that COPT6 resides at the plasma membrane and mediates
      copper accumulation when expressed in the Saccharomyces cerevisiae copper uptake
      mutant. Although the primary sequence of COPT6 contains the family conserved
      domains, including methionine-rich motifs in the extracellular N-terminal domain
      and a second transmembrane helix (TM2), it is different from the founding family
      member, S. cerevisiae Ctr1p. This conclusion was based on the finding that
      although the positionally conserved Met(106) residue in the TM2 of COPT6 is
      functionally essential, the conserved Met(27) in the N-terminal domain is not.
      Structure-function studies revealed that the N-terminal domain is dispensable for
      COPT6 function in copper-replete conditions but is important under copper
      limiting conditions. In addition, COPT6 interacts with itself and with its
      homolog, COPT1, unlike Ctr1p, which interacts only with itself. Analyses of the
      expression pattern showed that although COPT6 is expressed in different cell
      types of different plant organs, the bulk of its expression is located in the
      vasculature. We also show that COPT6 expression is regulated by copper
      availability that, in part, is controlled by a master regulator of copper
      homeostasis, SPL7. Finally, studies using the A. thaliana copt6-1 mutant and
      plants overexpressing COPT6 revealed its essential role during copper limitation
      and excess.

PMID- 22865878
TI  - Eukaryotic N-glycosylation occurs via the membrane-anchored C-terminal domain of
      the Stt3p subunit of oligosaccharyltransferase.
AB  - N-glycosylation is an essential and highly conserved protein modification. In
      eukaryotes, it is catalyzed by a multisubunit membrane-associated enzyme,
      oligosaccharyltransferase (OT). We report the high resolution structure of the C
      terminal domain of eukaryotic Stt3p. Unlike its soluble beta-sheet-rich
      prokaryotic counterparts, our model reveals that the C-terminal domain of yeast
      Stt3p is highly helical and has an overall oblate spheroid-shaped structure
      containing a membrane-embedded region. Anchoring of this protein segment to the
      endoplasmic reticulum membrane is likely to bring the membrane-embedded donor
      substrate closer, thus facilitating glycosylation efficiency. Structural
      comparison of the region near the WWDYG signature motif revealed that the
      acceptor substrate-binding site of yeast OT strikingly resembles its prokaryotic
      counterparts, suggesting a conserved mechanism of N-glycosylation from
      prokaryotes to eukaryotes. Furthermore, comparison of the NMR and cryo-EM
      structures of yeast OT revealed that the molecular architecture of this acceptor
      substrate-recognizing domain has interesting spatial specificity for interactions
      with other essential OT subunits.

PMID- 22865879
TI  - The liberation of CD44 intracellular domain modulates adenoviral vector transgene
      expression.
AB  - The success of gene therapy in the ocular environment is partly due to the
      presence of hyaluronan in vitreous. Here we explore the mechanism of hyaluronan
      mediated enhancement of adenoviral vector transgene expression. Introduction of
      hyaluronan receptor CD44 into CD44-negative cells followed by transduction in the
      presence of vitreous with an adenoviral vector containing an IL-12-coding
      transgene increases IL-12 secretion. We demonstrate that sequential CD44
      proteolysis is responsible for hyaluronan-mediated enhancement. Metalloproteinase
      or gamma-secretase inhibitors decrease adenoviral-mediated transgene expression.
      Deletion of these proteolytic sites in CD44 also inhibits transgene expression.
      Expression of CD44 with a mutation to prevent phosphorylation of serine 325
      inhibits the response to vitreous. Expression of the CD44 intracellular domain
      enhances transgene expression in the absence of vitreous. CD44-mediated
      enhancement of gene expression was observed with vectors using different
      promoters and appears because of an increase in mRNA production, not because of
      an increase in vector transduction as determined by quantitative RT-PCR and
      quantitative PCR, respectively. These data fit a model where the interaction of
      hyaluronan in vitreous and CD44 modulates transgene expression by initiating CD44
      proteolysis and release of the cytoplasmic domain, resulting in increased
      transgene transcription.

PMID- 22865880
TI  - XBP1S associates with RUNX2 and regulates chondrocyte hypertrophy.
AB  - BMP2 (bone morphogenetic protein 2) is known to activate unfolded protein
      response signaling molecules, including XBP1S and ATF6. However, the influence on
      XBP1S and ATF6 in BMP2-induced chondrocyte differentiation has not yet been
      elucidated. In this study, we demonstrate that BMP2 mediates mild endoplasmic
      reticulum stress-activated ATF6 and directly regulates XBP1S splicing in the
      course of chondrogenesis. XBP1S is differentially expressed during BMP2
      stimulated chondrocyte differentiation and exhibits prominent expression in
      growth plate chondrocytes. This expression is probably due to the activation of
      the XBP1 gene by ATF6 and splicing by IRE1a. ATF6 directly binds to the 5'
      flanking regulatory region of the XBP1 gene at its consensus binding elements.
      Overexpression of XBP1S accelerates chondrocyte hypertrophy, as revealed by
      enhanced expression of type II collagen, type X collagen, and RUNX2; however,
      knockdown of XBP1S via the RNAi approach abolishes hypertrophic chondrocyte
      differentiation. In addition, XBP1S associates with RUNX2 and enhances RUNX2
      induced chondrocyte hypertrophy. Altered expression of XBP1S in chondrocyte
      hypertrophy was accompanied by altered levels of IHH (Indian hedgehog) and PTHrP
      (parathyroid hormone-related peptide). Collectively, XBP1S may be a novel
      regulator of hypertrophic chondrocyte differentiation by 1) acting as a cofactor
      of RUNX2 and 2) affecting IHH/PTHrP signaling.

PMID- 22865881
TI  - Heparan sulfate 6-O-endosulfatases (Sulfs) coordinate the Wnt signaling pathways
      to regulate myoblast fusion during skeletal muscle regeneration.
AB  - Skeletal muscle regeneration is mediated by satellite cells (SCs). Upon injury,
      SCs undergo self-renewal, proliferation, and differentiation into myoblasts
      followed by myoblast fusion to form new myofibers. We previously showed that the
      heparan sulfate (HS) 6-O-endosulfatases (Sulf1 and -2) repress FGF signaling to
      induce SC differentiation during muscle regeneration. Here, we identify a novel
      role of Sulfs in myoblast fusion using a skeletal muscle-specific Sulf double
      null (Sulf(SK)-DN) mouse. Regenerating Sulf(SK)-DN muscles exhibit reduced
      canonical Wnt signaling and elevated non-canonical Wnt signaling. In addition, we
      show that Sulfs are required to repress non-canonical Wnt signaling to promote
      myoblast fusion. Notably, skeletal muscle-relevant non-canonical Wnt ligands lack
      HS binding capacity, suggesting that Sulfs indirectly repress this pathway.
      Mechanistically, we show that Sulfs reduce the canonical Wnt-HS binding and
      regulate colocalization of the co-receptor LRP5 with caveolin3. Therefore, Sulfs
      may increase the bioavailability of canonical Wnts for Frizzled receptor and
      LRP5/6 interaction in lipid raft, which may in turn antagonize non-canonical Wnt
      signaling. Furthermore, changes in subcellular distribution of active focal
      adhesion kinase (FAK) are associated with the fusion defect of Sulf-deficient
      myoblasts and upon non-canonical Wnt treatment. Together, our findings uncover a
      critical role of Sulfs in myoblast fusion by promoting antagonizing canonical Wnt
      signaling activities against the noncanonical Wnt pathway during skeletal muscle
      regeneration.

PMID- 22865882
TI  - Physical and functional interactions between Drosophila homologue of
      Swc6/p18Hamlet subunit of the SWR1/SRCAP chromatin-remodeling complex with the
      DNA repair/transcription factor TFIIH.
AB  - The multisubunit DNA repair and transcription factor TFIIH maintains an intricate
      cross-talk with different factors to achieve its functions. The p8 subunit of
      TFIIH maintains the basal levels of the complex by interacting with the p52
      subunit. Here, we report that in Drosophila, the homolog of the p8 subunit (Dmp8)
      is encoded in a bicistronic transcript with the homolog of the Swc6/p18(Hamlet)
      subunit (Dmp18) of the SWR1/SRCAP chromatin remodeling complex. The SWR1 and
      SRCAP complexes catalyze the exchange of the canonical histone H2A with the H2AZ
      histone variant. In eukaryotic cells, bicistronic transcripts are not common, and
      in some cases, the two encoded proteins are functionally related. We found that
      Dmp18 physically interacts with the Dmp52 subunit of TFIIH and co-localizes with
      TFIIH in the chromatin. We also demonstrated that Dmp18 genetically interacts
      with Dmp8, suggesting that a cross-talk might exist between TFIIH and a component
      of a chromatin remodeler complex involved in histone exchange. Interestingly, our
      results also show that when the level of one of the two proteins is decreased and
      the other maintained, a specific defect in the fly is observed, suggesting that
      the organization of these two genes in a bicistronic locus has been selected
      during evolution to allow co-regulation of both genes.

PMID- 22865883
TI  - Coordinated action of hypoxia-inducible factor-1alpha and beta-catenin in
      androgen receptor signaling.
AB  - The androgen receptor (AR) acts as a ligand-dependent transcriptional factor and
      plays a critical role in the development and progression of androgen-dependent
      and castration-resistant prostate cancer. Castration results in hypoxia in
      prostate cancer cells, and hypoxia enhances transcriptional activity of AR
      through hypoxia-inducible factor (HIF)-1alpha at low serum androgen levels
      mimicking the castration-resistant stage. However, HIF-1alpha is necessary but
      not sufficient for hypoxia-activated AR transactivation, and the molecular
      mechanism that regulates AR function in castration-resistant prostate cancer
      remains unclear. Here, we report that beta-catenin is required for HIF-1alpha
      mediated AR transactivation in hypoxic LNCaP prostate cancer cells under low
      androgen conditions. HIF-1alpha and beta-catenin coordinately enhanced AR N
      terminal and C-terminal interaction. beta-Catenin accumulated in the nucleus in
      the HIF-1alpha protein-positive cells of LNCaP xenografts in castrated mice. In
      LNCaP cells, when HIF-1alpha was knocked down or was exogenously expressed in the
      cytoplasm, hypoxia-induced nuclear localization of beta-catenin was inhibited.
      beta-Catenin formed a complex with HIF-1alpha both in the nucleus and in the
      cytoplasm. Hypoxia increased the amount of a complex composed of AR and beta
      catenin, and knockdown of HIF-1alpha attenuated the recruitment of AR and beta
      catenin to the androgen response elements (AREs) of androgen-responsive genes.
      Furthermore, together with beta-catenin, HIF-1alpha bound to the AREs in the
      presence of androgen. These results demonstrate that (i) HIF-1alpha and beta
      catenin coordinately enhance AR transactivation by accelerating N-terminal and C
      terminal interaction; (ii) HIF-1alpha promotes nuclear translocation of beta
      catenin in hypoxia; and (iii) AR, HIF-1alpha, and beta-catenin form a ternary
      complex on AREs.

PMID- 22865884
TI  - FOXO1 transcription factor inhibits luteinizing hormone beta gene expression in
      pituitary gonadotrope cells.
AB  - Synthesis of luteinizing hormone (LH) is tightly controlled by a complex network
      of hormonal signaling pathways that can be modulated by metabolic cues, such as
      insulin. One group of candidate genes that may be regulated by insulin signaling
      in pituitary gonadotrope cells is the FOXO subfamily of forkhead transcription
      factors. In this study we investigated whether FOXO1 is expressed in gonadotropes
      and if it can modulate LH beta-subunit (Lhb) gene expression. We demonstrated
      that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling
      increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K-dependent
      manner. We also showed that FOXO1 repressed basal transcription and gonadotropin
      releasing hormone (GnRH) induction of both the murine and human LHB genes in
      LbetaT2 cells, suggesting that FOXO1 regulation of LHB transcription may be
      conserved between rodents and humans. Although we did not detect FOXO1 binding to
      the proximal Lhb promoter, the FOXO1 DNA binding domain was necessary for the
      suppression, suggesting that FOXO1 exerts its effect through protein-protein
      interactions with transcription factors/cofactors required for Lhb gene
      expression. FOXO1 repression mapped to the proximal Lhb promoter containing
      steroidogenic factor 1 (SF1), pituitary homeobox 1 (PTX1), and early growth
      response protein 1 (EGR1) binding elements. Additionally, FOXO1 blocked induction
      of the Lhb promoter with overexpressed SF1, PTX1, and EGR1, indicating that FOXO1
      repression occurs via these transcription factors but not through regulation of
      their promoters. In summary, we demonstrate that FOXO1 phosphorylation and
      cellular localization is regulated by insulin signaling in gonadotropes and that
      FOXO1 inhibits Lhb transcription. Our study also suggests that FOXO1 may play an
      important role in controlling LH levels in response to metabolic cues.

PMID- 22865885
TI  - Family with sequence similarity 60A (FAM60A) protein is a cell cycle-fluctuating
      regulator of the SIN3-HDAC1 histone deacetylase complex.
AB  - The SIN3A-HDAC complex deacetylates histones thereby repressing gene
      transcription. Here we describe family with sequence similarity 60A (FAM60A), a
      cell cycle-regulated protein that binds to the SIN3-HDAC complex. FAM60A
      expression peaks during G(1) and S phases of the cell cycle in U2OS cells, in a
      manner similar to the G(1) regulator cyclin D1, which is a known target of SIN3
      HDAC. In this light we found that FAM60A binds to SIN3-HDAC-regulated promoters
      such as cyclin D1 in G(1) and S phases. Cells depleted of FAM60A show increased
      histone acetylation at the cyclin D1 promoter and elevated levels of cyclin D1
      mRNA and protein. Furthermore, depletion of FAM60A altered the periodic
      association of HDAC1 with the cyclin D1 promoter, increased cyclin D1 expression
      at all cell cycle phases, and caused premature S phase entry. The data in this
      study introduce FAM60A as a novel regulator of SIN3-HDAC function and gene
      expression.

PMID- 22865886
TI  - Structural insights into the anti-HIV activity of the Oscillatoria agardhii
      agglutinin homolog lectin family.
AB  - Oscillatoria agardhii agglutinin homolog (OAAH) proteins belong to a recently
      discovered lectin family. All members contain a sequence repeat of ~66 amino
      acids, with the number of repeats varying among different family members. Apart
      from data for the founding member OAA, neither three-dimensional structures,
      information about carbohydrate binding specificities, nor antiviral activity data
      have been available up to now for any other members of the OAAH family. To
      elucidate the structural basis for the antiviral mechanism of OAAHs, we
      determined the crystal structures of Pseudomonas fluorescens and Myxococcus
      xanthus lectins. Both proteins exhibit the same fold, resembling the founding
      family member, OAA, with minor differences in loop conformations. Carbohydrate
      binding studies by NMR and x-ray structures of glycan-lectin complexes reveal
      that the number of sugar binding sites corresponds to the number of sequence
      repeats in each protein. As for OAA, tight and specific binding to alpha3,alpha6
      mannopentaose was observed. All the OAAH proteins described here exhibit potent
      anti-HIV activity at comparable levels. Altogether, our results provide
      structural details of the protein-carbohydrate interaction for this novel lectin
      family and insights into the molecular basis of their HIV inactivation
      properties.

PMID- 22865887
TI  - A scalable approach to prevent teratoma formation of human embryonic stem cells.
AB  - As the renewable source of all cell types in the body, human embryonic stem cells
      (hESCs) hold great promise for human cell therapy. However, one major bottleneck
      that hinders the clinic application of hESCs is that hESCs remaining with their
      differentiated derivatives pose cancer risk by forming teratomas after
      transplantation. NANOG is a critical pluripotency factor specifically expressed
      in hESCs but rarely in their differentiated derivatives. By introducing a
      hyperactive variant of herpes simplex virus thymidine kinase gene into the 3'
      untranslated region of the endogenous NANOG gene of hESCs through homologous
      recombination, we developed a safe and highly scalable approach to efficiently
      eliminate the teratoma risk associated with hESCs without apparent negative
      impact on their differentiated cell types. As thymidine kinase is widely used in
      human gene therapy trials and is the therapeutic target of U. S. Food and Drug
      Administration-approved drugs, our strategy could be effectively applied to the
      clinic development of hESC-based human cell therapy.

PMID- 22865888
TI  - Factors that differentiate the H-bond strengths of water near the Schiff bases in
      bacteriorhodopsin and Anabaena sensory rhodopsin.
AB  - Bacteriorhodopsin (BR) functions as a light-driven proton pump, whereas Anabaena
      sensory rhodopsin (ASR) is believed to function as a photosensor despite the high
      similarity in their protein sequences. In Fourier transform infrared (FTIR)
      spectroscopic studies, the lowest O-D stretch for D(2)O was observed at ~2200 cm(
      1) in BR but was significantly higher in ASR (>2500 cm(-1)), which was previously
      attributed to a water molecule near the Schiff base (W402) that is H-bonded to
      Asp-85 in BR and Asp-75 in ASR. We investigated the factors that differentiate
      the lowest O-D stretches of W402 in BR and ASR. Quantum mechanical/molecular
      mechanical calculations reproduced the H-bond geometries of the crystal
      structures, and the calculated O-D stretching frequencies were corroborated by
      the FTIR band assignments. The potential energy profiles indicate that the
      smaller O-D stretching frequency in BR originates from the significantly higher
      pK(a)(Asp-85) in BR relative to the pK(a)(Asp-75) in ASR, which were calculated
      to be 1.5 and -5.1, respectively. The difference is mostly due to the influences
      of Ala-53, Arg-82, Glu-194-Glu-204, and Asp-212 on pK(a)(Asp-85) in BR and the
      corresponding residues Ser-47, Arg-72, Ser-188-Asp-198, and Pro-206 on pK(a)(Asp
      75) in ASR. Because these residues participate in proton transfer pathways in BR
      but not in ASR, the presence of a strongly H-bonded water molecule near the
      Schiff base ultimately results from the proton-pumping activity in BR.

PMID- 22865889
TI  - Myocardial relaxation, restoring forces, and early-diastolic load are independent
      determinants of left ventricular untwisting rate.
AB  - BACKGROUND: Peak left ventricular (LV) untwisting rate (UTR) has been introduced
      as a clinical marker of diastolic function. This study investigates if early
      diastolic load and restoring forces are determinants of UTR in addition to the
      rate of LV relaxation. METHODS AND RESULTS: In 10 anesthetized dogs we measured
      UTR by sonomicrometry and speckle tracking echocardiography at varying LV
      preloads, increased contractility, and myocardial ischemia. UTR was calculated as
      the time derivative of LV twist. Because preload modified end-diastolic twist, LV
      systolic twist was calculated in absolute terms with reference to the end
      diastolic twist configuration at baseline. Relaxation rate was measured as the
      time constant (tau) of LV isovolumic pressure decay. Early-diastolic load was
      measured as LV pressure at the time of mitral valve opening. Circumferential
      longitudinal shear strain was used as an index of restoring forces. In a
      multivariable mixed model analysis a strong association was observed between UTR
      and LV pressure at the time of mitral valve opening (parameter estimate
      [beta]=6.9; P<0.0001), indicating an independent effect of early-diastolic load.
      Furthermore, the associations between UTR and circumferential-longitudinal shear
      strain (beta=-11.3; P<0.0001) and tau (beta=-1.6, P<0.003) were consistent with
      independent contributions from restoring forces and rate of relaxation. Maximal
      UTR before mitral valve opening, however, was determined only by relaxation rate
      and restoring forces. CONCLUSIONS: The present study indicates that early
      diastolic load, restoring forces, and relaxation rate are independent
      determinants of peak UTR. However, only relaxation rate and restoring forces
      contributed to UTR during isovolumic relaxation.

PMID- 22865890
TI  - The cell motility modulator Slit2 is a potent inhibitor of platelet function.
AB  - BACKGROUND: Vascular injury and atherothrombosis involve vessel infiltration by
      inflammatory leukocytes, migration of medial vascular smooth muscle cells to the
      intimal layer, and ultimately acute thrombosis. A strategy to simultaneously
      target these pathological processes has yet to be identified. The secreted
      protein, Slit2, and its transmembrane receptor, Robo-1, repel neuronal migration
      in the developing central nervous system. More recently, it has been appreciated
      that Slit2 impairs chemotaxis of leukocytes and vascular smooth muscle cells
      toward diverse inflammatory attractants. The effects of Slit2 on platelet
      function and thrombus formation have never been explored. METHODS AND RESULTS: We
      detected Robo-1 expression in human and murine platelets and megakaryocytes and
      confirmed its presence via immunofluorescence microscopy and flow cytometry. In
      both static and shear microfluidic assays, Slit2 impaired platelet adhesion and
      spreading on diverse extracellular matrix substrates by suppressing activation of
      Akt. Slit2 also prevented platelet activation on exposure to ADP. In in vivo
      studies, Slit2 prolonged bleeding times in murine tail bleeding assays. Using
      intravital microscopy, we found that after mesenteric arteriolar and carotid
      artery injury, Slit2 delayed vessel occlusion time and prevented the stable
      formation of occlusive arteriolar thrombi. CONCLUSIONS: These data demonstrate
      that Slit2 is a powerful negative regulator of platelet function and thrombus
      formation. The ability to simultaneously block multiple events in vascular injury
      may allow Slit2 to effectively prevent and treat thrombotic disorders such as
      myocardial infarction and stroke.

PMID- 22865891
TI  - Ascending-ramp biphasic waveform has a lower defibrillation threshold and
      releases less troponin I than a truncated exponential biphasic waveform.
AB  - BACKGROUND: We tested the hypothesis that the shape of the shock waveform affects
      not only the defibrillation threshold but also the amount of cardiac damage.
      METHODS AND RESULTS: Defibrillation thresholds were determined for 11 waveforms-3
      ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase
      biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic
      waveform-in 6 pigs with electrodes in the right ventricular apex and superior
      vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and
      16-millisecond first phases and a 3.5-millisecond rectilinear second phase that
      was half the voltage of the first phase. The exponential biphasic waveform had a
      60% first-phase and a 50% second-phase tilt. In a second study, we attempted to
      defibrillate after 10 seconds of ventricular fibrillation with a single ~30-J
      shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8
      millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin
      I blood levels were determined before and 2 to 10 hours after the shock. The
      lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp
      (14.6+/-7.3 J [mean+/-SD]), which was significantly less than for the truncated
      exponential (19.6+/-6.3 J). Six hours after shock, troponin I was significantly
      less for the ascending-ramp waveform (0.80+/-0.54 ng/mL) than for the truncated
      exponential (1.92+/-0.47 ng/mL) or the rectilinear waveform (1.17+/-0.45 ng/mL).
      CONCLUSIONS: The ascending ramp has a significantly lower defibrillation
      threshold and at ~30 J causes 58% less troponin I release than the truncated
      exponential biphasic shock. Therefore, the shock waveform affects both the
      defibrillation threshold and the amount of cardiac damage.

PMID- 22865892
TI  - Cyclooxygenase-2-derived prostacyclin regulates arterial thrombus formation by
      suppressing tissue factor in a sirtuin-1-dependent-manner.
AB  - BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 increase the risk of
      myocardial infarction and thrombotic events, but the responsible mechanisms are
      not fully understood. METHODS AND RESULTS: We found that ferric chloride-induced
      arterial thrombus formation was significantly greater in COX-2 knockout compared
      with wild-type mice. Cross-transfusion experiments excluded the likelihood that
      COX-2 knockout platelets, despite enhanced aggregation responses to collagen and
      thrombin, are responsible for increased arterial thrombus formation in COX-2
      knockout mice. Importantly, we observed that COX-2 deletion decreased
      prostacyclin synthase and production and peroxisome proliferator-activated
      receptor- and sirtuin-1 (SIRT1) expression, with consequent increased
      upregulation of tissue factor (TF), the primary initiator of blood coagulation.
      Treatment of wild-type mice with a prostacyclin receptor antagonist or a
      peroxisome proliferator-activated receptor-delta antagonist, which predisposes to
      arterial thrombosis, decreased SIRT1 expression and increased TF activity.
      Conversely, exogenous prostacyclin or peroxisome proliferator-activated receptor
      delta agonist completely reversed the thrombotic phenotype in COX-2 knockout
      mice, restoring normal SIRT1 levels and reducing TF activity. Furthermore,
      inhibition of SIRT1 increased TF expression and activity and promoted generation
      of occlusive thrombi in wild-type mice, whereas SIRT1 activation was sufficient
      to decrease abnormal TF activity and prothrombotic status in COX-2 knockout mice.
      CONCLUSIONS: Modulation of SIRT1 and hence TF by prostacyclin/peroxisome
      proliferator-activated receptor-delta pathways not only represents a new
      mechanism in controlling arterial thrombus formation but also might be a useful
      target for therapeutic intervention in the atherothrombotic complications
      associated with COX-2 inhibitors.

PMID- 22865894
TI  - Clinical and immunological remarks about TAP deficiency.

PMID- 22865895
TI  - Problems with the Analyses of the Ribosomal Allosteric Three-site Model.

PMID- 22865893
TI  - mRNA localization and translational control in Drosophila oogenesis.
AB  - Localization of an mRNA species to a particular subcellular region can complement
      translational control mechanisms to produce a restricted spatial distribution of
      the protein it encodes. mRNA localization has been studied most in asymmetric
      cells such as budding yeast, early embryos, and neurons, but the process is
      likely to be more widespread. This article reviews the current state of knowledge
      about the mechanisms of mRNA localization and its functions in early embryonic
      development, focusing on Drosophila where the relevant knowledge is most
      advanced. Links between mRNA localization and translational control mechanisms
      also are examined.

PMID- 22865896
TI  - Total thyroidectomy in patients with amiodarone-induced thyrotoxicosis and severe
      left ventricular systolic dysfunction.
AB  - CONTEXT: Patients with amiodarone-induced thyrotoxicosis (AIT) and left
      ventricular (LV) systolic dysfunction have a high mortality rate. Usually,
      medical therapy is the first choice for AIT patients, whereas the role of the
      thyroidectomy is unsettled. OBJECTIVE: The objective of the study was to evaluate
      the effect of a total thyroidectomy on cardiac function and survival of AIT
      patients with severe LV systolic dysfunction. DESIGN: This was a retrospective
      cohort study. SETTINGS: The study was conducted at a tertiary university center.
      PATIENTS: All AIT patients (n=24; nine patients with type 1 AIT, 15 patients with
      type 2 AIT) referred to the Department of Endocrinology and submitted to a total
      thyroidectomy at the Department of Surgery, both at the University of Pisa,
      during the years 1997-2010. INTERVENTION: The intervention was a total
      thyroidectomy. MAIN OUTCOME MEASURE: LV ejection fraction (EF) after the
      thyroidectomy and survival in December 2011 were measured. RESULTS: All enrolled
      patients had previously undergone to medical treatment for AIT, as appropriate,
      without achieving euthyroidism. Patients with moderate to severe LV systolic
      dysfunction (EF<40%, group 1, n=9) or with mild systolic dysfunction
      (40%<=EF<=50%, group 2, n=5) were compared with patients with normal systolic
      function (EF>50%, group 3, n=10). Two months after thyroidectomy, under
      levothyroxine replacement therapy, LVEF improved in patients with LV systolic
      dysfunction, particularly in those of group 1, in whom it increased from 28.2+/
      7.2 to 38.3+/-6% (P=0.007). On the contrary, LVEF did not significantly change in
      group 3 (from 57.1+/-3.0 to 59.8+/-6.6%, P=0.242). The mean follow-up was 67+/-42
      months. No death occurred during and 2 months after surgery. One death occurred
      in one patient of group 1, 30 months after the thyroidectomy, due to acute
      myocardial infarction. No patient had relevant complications of thyroidectomy.
      CONCLUSIONS: Total thyroidectomy, by rapidly restoring euthyroidism, may improve
      cardiac function and reduce the risk of mortality in AIT patients with severe LV
      dysfunction.

PMID- 22865897
TI  - Nonmodulation as the mechanism for salt sensitivity of blood pressure in
      individuals with hypertension and type 2 diabetes mellitus.
AB  - CONTEXT: It is assumed that in individuals with type 2 diabetes mellitus (T2DM),
      blood pressure sensitivity to salt intake and the frequency of a low renin state
      are both increased compared with the nondiabetic population. However, studies
      supporting these assumptions may have been confounded by participant inclusion
      criteria, and study results may reflect target organ damage. OBJECTIVE: The
      objective of this study was to examine in a cohort of T2DM 1) the frequency of
      salt sensitivity of blood pressure and 2) whether alterations of the renin
      angiotensin-aldosterone system (RAAS) contribute to salt sensitivity in this
      population. DESIGN, PATIENTS, AND METHODS: Within participants of the HyperPATH
      cohort, four groups were analyzed: 1) T2DM with hypertension (HTN), n=51; 2) T2DM
      without HTN, n=30; 3) HTN only, n=451; and 4) normotensive, n=209. Phenotype
      studies were conducted after participants completed two dietary phases: liberal
      sodium (200 mmol/d) and low sodium (10 mmol/d) for 7 d each. Participants were
      admitted overnight to a clinical research center after each diet, and supine
      measurements of the RAAS before and after a 60-min angiotensin II infusion (3
      ng/kg.min) were obtained. RESULTS: Multivariate regression analysis demonstrated
      that T2DM status (all individuals with T2DM vs. individuals without T2DM) was not
      associated with the change in mean arterial pressure between the low and liberal
      sodium diets after accounting for age, gender, body mass index, race, and
      baseline blood pressure (T2DM status, P=0.5). Furthermore, two intermediate
      phenotypes of altered RAAS, low renin, and nonmodulation (NMOD), were associated
      with salt-sensitive blood pressure but occurred at different frequencies in the
      T2DM-HTN and HTN groups (low renin, 12% T2DM-HTN vs. 29% HTN; NMOD, 41% T2DM-HTN
      vs. 27% HTN; P=0.01). CONCLUSION: The frequency of NMOD in participants with T2DM
      was significantly higher compared with HTN, suggesting that the salt sensitivity
      often seen in T2DM is driven by NMOD.

PMID- 22865898
TI  - Physical activity in relation to serum sclerostin, insulin-like growth factor-1,
      and bone turnover markers in healthy premenopausal women: a cross-sectional and a
      longitudinal study.
AB  - CONTEXT: There is limited information on the effects of mechanical loading caused
      by physical activity (PA) on sclerostin, IGF-I, and bone turnover markers (BTM).
      OBJECTIVE: The objective of the investigation was to study the relationships
      between serum sclerostin, serum-IGF-I (s-IGF-I), BTM, and the PA level in
      premenopausal women and to discern how 8 wk of PA training (PAT) affects the
      serum levels of sclerostin, IGF-I, and BTM. DESIGN: This was a cross-sectional
      study with a subgroup followed up longitudinally. SETTINGS AND SUBJECTS: A total
      of 1235 randomly selected premenopausal women were cross-sectionally studied. We
      also followed up 58 of these women longitudinally during an 8-wk course of PAT (4
      d/wk) and compared them with 62 controls. All women were medically examined, and
      bone mineral density (BMD) and serum levels of sclerostin, s-IGF-I, and BTM were
      determined. RESULTS: Women with PA of greater than 120 min/wk showed
      significantly lower serum sclerostin (by 36.8%) but higher s-IGF-I (by 107%)
      levels than sedentary controls. Bone formation markers were also higher in the PA
      greater than 120 min/wk group compared with the sedentary controls. In the
      longitudinal study, the 8-wk PAT program led to a decrease in serum sclerostin
      (by 33.9%, P<0.0001) but increases in the serum levels of the bone-formation
      markers and IGF-I (s-IGF-I by 74.2%, P<0.0001). CONCLUSIONS: This study
      demonstrates that even minor changes in PA are associated with effects on serum
      levels of sclerostin, IGF-I, and BTM and suggests that sclerostin could be a link
      between mechanical loading and disuse osteoporosis in humans.

PMID- 22865899
TI  - Pubertal timing, androgens, and obesity phenotypes in women at midlife.
AB  - CONTEXT: Individuals with metabolically healthy or benign obesity vs. unhealthy
      or at risk obesity have been distinguished; however, the predisposing factors for
      developing these phenotypes are poorly understood. OBJECTIVE: Our objective was
      to examine pubertal timing marked by menarcheal age in relation to at-risk obese,
      benign obese, and healthy normal-weight phenotypes at midlife and to characterize
      the potential role of androgens, marked by the free androgen index (FAI), in
      accounting for any associations between menarcheal age and obesity phenotype.
      DESIGN: The study was cross-sectional. SETTING AND PARTICIPANTS: Participants
      included a multiethnic community sample of 989 premenopausal women ages 25-45 yr
      (mean=35.2 yr; sd=5.5 yr). MAIN OUTCOME MEASURE: Membership in at-risk obese,
      benign obese, and healthy normal-weight groups was defined by body mass index and
      number of metabolic syndrome components. RESULTS: With each 1-yr increase in
      menarcheal age, the probability of having the at-risk obese compared with the
      healthy normal-weight phenotype decreased by 22%. This association attenuated
      when FAI was covaried, suggesting androgen levels may account for this
      association. In addition, higher FAI was independently related to having the at
      risk obese compared with the healthy normal-weight phenotype as well as having
      the at-risk compared with the benign obese phenotype (all P<0.05). CONCLUSIONS:
      Younger menarcheal age is associated with having the metabolically unhealthy
      obesity phenotype compared with the healthy normal-weight phenotype at midlife.
      This relation may be driven by levels of bioavailable androgens, which were
      especially elevated among women with the at-risk obesity phenotype.

PMID- 22865900
TI  - Moderate ovarian stimulation does not increase the incidence of human embryo
      chromosomal abnormalities in in vitro fertilization cycles.
AB  - CONTEXT: A high chromosomal abnormalities rate has been observed in human embryos
      derived from in vitro fertilization (IVF) treatments. The real incidence in
      natural cycles has been poorly studied, so whether this frequency may be induced
      by external factors, such as use of gonadotropins for ovarian stimulation,
      remains unknown. DESIGN: We conducted a prospective cohort study in a University
      affiliated private infertility clinic with a comparison between unstimulated and
      stimulated ovarian cycles in the same women. Preimplantation genetic screening by
      fluorescence in situ hybridization was performed in all viable d 3 embryos.
      OBJECTIVE: The primary objective was to compare the incidence of embryo
      chromosomal abnormalities in an unstimulated cycle and in an ulterior moderate
      ovarian stimulated cycle. Secondary outcome measures were embryo quality,
      blastocyst rate of biopsied embryos, number of normal blastocysts per donor, type
      of chromosomal abnormalities, and clinical outcome. RESULTS: One hundred eighty
      five oocyte donors were initially recruited for the unstimulated cycle, and
      preimplantation genetic screening could be performed in 51 of them, showing 35.3%
      of embryo chromosomal abnormalities. Forty-six of them later completed a
      stimulated cycle. The sperm donor sample was the same for both cycles. The
      proportion of embryos displaying abnormalities in the unstimulated cycle was
      34.8% (16 of 46), whereas it was 40.6% (123 of 303) in the stimulated cycle with
      risk difference=5.8 [95% confidence interval (CI)=-20.6-9.0], and relative
      risk=1.17 (95% CI=0.77-1.77) (P=0.45). When an intrasubject comparison was made,
      the abnormalities rate was 34.8% (95% CI=20.5-49.1) in the unstimulated cycle and
      38.2% (95% CI=30.5-45.8) in the stimulated cycle [risk difference=3.4 (95% CI=
      17.9-11.2); P=0.64]. No differences were observed for embryo quality and type of
      chromosomal abnormalities. CONCLUSIONS: Moderate ovarian stimulation in young
      normo-ovulatory women does not significantly increase the embryo aneuploidies
      rate in in vitro fertilization-derived human embryos as compared with an
      unstimulated cycle. Whether these results can be extrapolated to infertile
      patients is still unknown.

PMID- 22865901
TI  - Longitudinal assessment of bone density and structure in childhood survivors of
      acute lymphoblastic leukemia without cranial radiation.
AB  - PURPOSE: Children with acute lymphoblastic leukemia (ALL) are at risk for
      impaired bone accrual. This peripheral quantitative computed tomography study
      assessed changes in bone mineral density (BMD) and structure after completion of
      ALL treatment. METHODS: Fifty ALL participants, ages 5-22 yr, were enrolled
      within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral
      quantitative computed tomography scans were performed at enrollment and 12 months
      later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD),
      cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more
      than 650 reference participants. Multivariable linear regression models examined
      determinants of changes in Z-scores. RESULTS: At enrollment, mean TrabBMD (
      1.03+/-1.34) and CortBMD (-0.84+/-1.05) Z-scores were low (both P<0.001) compared
      with reference participants. TrabBMD and CortBMD Z-scores increased to -0.58+/
      1.41 and -0.51+/-0.91 over 1 yr, respectively (both P<0.001). Changes in cortical
      outcomes varied according to the interval since completion of therapy. Among
      those enrolled less than 6 months after therapy, CortArea Z-scores increased and
      CortBMD Z-scores decreased (both P<0.01). Among those enrolled 6 months or more
      after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased
      (P<0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r=
      0.32, P<0.001). Cumulative glucocorticoid exposure, leukemia risk status, and
      antimetabolite chemotherapy were not associated with outcomes. CONCLUSION:
      TrabBMD was low after completion of ALL therapy and improved significantly. Early
      increases in cortical dimensions were associated with declines in CortBMD;
      however, participants further from ALL therapy demonstrated stable cortical
      dimensions and increases in CortBMD, potentially reflecting the time necessary to
      mineralize newly formed bone.

PMID- 22865902
TI  - Vitamin D3 supplementation has no effect on conventional cardiovascular risk
      factors: a parallel-group, double-blind, placebo-controlled RCT.
AB  - CONTEXT: Observational studies show an association between low vitamin D status
      assessed by circulating 25-hydroxyvitamin D and cardiovascular events and
      mortality. Data from randomized controlled trials are limited. OBJECTIVE: The aim
      of this study was to test whether daily doses of vitamin D(3) at 400 or 1000 IU/d
      for 1 yr affected conventional markers of cardiovascular disease (CVD) risk.
      DESIGN: We conducted a parallel-group, double-blind, placebo-controlled
      randomized controlled trial. Randomization was computer generated. Participants
      and study investigators were blinded to intervention groupings throughout the
      trial. SETTING: The study was conducted at the Clinical Research Facility,
      University of Aberdeen, United Kingdom. PARTICIPANTS: A total of 305 healthy
      postmenopausal women aged 60-70 yr were recruited for the study. INTERVENTION:
      Each woman received a daily capsule of 400 or 1000 IU vitamin D(3) or placebo
      randomly allocated. MAIN OUTCOME MEASURES: Primary outcomes were serum lipid
      profile [total, high-density lipoprotein, and low-density lipoprotein
      cholesterol; triglycerides; and apolipoproteins A-1 and B100], insulin resistance
      (homeostatic model assessment), inflammatory biomarkers (high-sensitivity C
      reactive protein, IL-6, soluble intracellular adhesion molecule-1), and blood
      pressure. RESULTS: A total of 265 (87%) participants completed all study visits.
      Small differences between groups for serum apolipoprotein B100 change [repeated
      measures ANOVA, P=0.04; mean (sd), -1.0 (10.0) mg/dl (400 IU); -1.0 (10.0) mg/dl
      (1000 IU); and +0.02 (10.0) mg/dl (placebo)] were not considered clinically
      significant. Other systemic markers for CVD risk remained unchanged. There was
      significant seasonal variation in systolic and diastolic blood pressure
      independent of vitamin D dose (P<0.001, linear mixed model). Mean (sd) reduction
      in systolic blood pressure from winter to summer was -6.6 (10.8) mm Hg.
      CONCLUSIONS: Improving vitamin D status through dietary supplementation is
      unlikely to reduce CVD risk factors. Confounding of seasonality should be
      recognized and addressed in future studies of vitamin D.

PMID- 22865903
TI  - Fracture risk assessment without race/ethnicity information.
AB  - CONTEXT: Dual-energy x-ray absorptiometry-derived bone mineral density (BMD) does
      not explain interracial differences in fracture risk; thus, BMD-based fracture
      risk assessment requires patient race/ethnicity information and ethnicity
      specific BMD reference databases. OBJECTIVE: The objective of the study was to
      investigate whether composite femoral neck strength indices, which integrate dual
      energy x-ray absorptiometry-derived femoral neck size, femoral neck BMD, and body
      size, will allow fracture risk assessment without requiring race/ethnicity
      information. DESIGN: This was a prospective cohort study. SETTING AND
      PARTICIPANTS: A total of 1940 community-dwelling women aged 42-53 yr from four
      race/ethnicity groups (968 Caucasian, 512 African-American, 239 Japanese, and 221
      Chinese) were followed up for 9 yr. OUTCOME MEASUREMENTS: Self-reported,
      nondigital, noncraniofacial fractures were measured. RESULTS: Two hundred and two
      women (10.4%) sustained fractures and 82 (4.3%) had minimum-trauma fractures.
      Each sd increment in any of the strength indices was associated with a 34-41%
      reduction in fracture hazard over 9 yr (each P<0.001). Race/ethnicity predicted
      fracture hazard independent of BMD (P=0.02) but did not predict fracture hazard
      independent of any of the composite indices (P=0.11-0.22). Addition of
      race/ethnicity did not improve risk discrimination ability of the strength
      indices, but did significantly improve the discrimination ability of BMD. The
      discrimination ability of BMD with race/ethnicity was not statistically different
      from that of any of the strength indices without race/ethnicity. CONCLUSIONS:
      Composite strength indices of the femoral neck can predict fracture risk without
      race/ethnicity information as accurately as bone mineral density does in
      combination with race/ethnicity information and therefore would allow risk
      prediction in people of mixed race/ethnicity and in groups without a BMD
      reference database.

PMID- 22865904
TI  - GADA titer-related risk for organ-specific autoimmunity in LADA subjects
      subdivided according to gender (NIRAD study 6).
AB  - CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous
      population wherein, based on glutamic acid decarboxylase antibody (GADA) titer,
      different subgroups of subjects can be identified. OBJECTIVE: The aim of the
      present study was to evaluate GADA titer-related risk for beta-cell and other
      organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune
      diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were
      characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc
      transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH),
      tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS:
      High GADA titer compared to low GADA titer showed a significantly higher
      prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P<=0.04 for
      all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A
      significant decreasing trend was observed from high GADA to low GADA and to T2DM
      subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for
      trend<=0.001). TPO was the only antibody showing a different prevalence between
      gender; low GADA titer and T2DM female patients had a higher frequency of TPO
      antibody compared to males (P=0.0004 and P=0.0006, respectively), where the
      presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to
      low GADA titer. After subdividing high and low GADA titer subjects according to
      the number of antibodies, we observed that 73.3% of high GADA titer subjects were
      positive for at least one or more antibodies, compared to 38.3% of low GADA titer
      (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a
      profile of more severe autoimmunity and, in male gender, specifically predisposed
      to thyroid autoimmunity. A regular screening for other antibodies is recommended
      in LADA patients according to GADA titer and gender.

PMID- 22865905
TI  - Clinical review: The thyroid in mind: cognitive function and low thyrotropin in
      older people.
AB  - CONTEXT: Several studies have reported an association between low serum TSH, or
      subclinical hyperthyroidism (SH), and dementia, but little emphasis has been
      placed on this field because not all studies have demonstrated the same
      association. We performed a detailed systematic review to assess the evidence
      available to support the association between these two conditions. METHODS: We
      performed a systematic search through the PubMed, Embase (1996 to 2012 wk 4),
      Cochrane Library, and Medline (1996 to January wk 4, 2012) electronic databases
      using key search terms encompassing subclinical hyperthyroidism, TSH, dementia,
      and cognitive impairment. RESULTS: This review examines the 23 studies that
      provide information about the association between SH or lower serum TSH within
      the reference range and cognition. Fourteen of these studies, including several
      well-designed and well-powered cross-sectional and longitudinal analyses, have
      shown a consistent finding of an association between SH with cognitive impairment
      or dementia. CONCLUSION: There is a substantial body of evidence to support the
      association between SH and cognitive impairment, but there is no clear
      mechanistic explanation for these associations. Nor is there an indication that
      antithyroid treatment might ameliorate dementia. Larger and more detailed
      prospective longitudinal or randomized controlled trials are required to inform
      these important questions.

PMID- 22865906
TI  - Fanconi-Bickel syndrome and autosomal recessive proximal tubulopathy with
      hypercalciuria (ARPTH) are allelic variants caused by GLUT2 mutations.
AB  - CONTEXT: Many inherited disorders of calcium and phosphate homeostasis are
      unexplained at the molecular level. OBJECTIVE: The objective of the study was to
      identify the molecular basis of phosphate and calcium abnormalities in two
      unrelated, consanguineous families. PATIENTS: The affected members in family 1
      presented with rickets due to profound urinary phosphate-wasting and
      hypophosphatemic rickets. In the previously reported family 2, patients presented
      with proximal renal tubulopathy and hypercalciuria yet normal or only mildly
      increased urinary phosphate excretion. METHODS: Genome-wide linkage scans and
      direct nucleotide sequence analyses of candidate genes were performed. Transport
      of glucose and phosphate by glucose transporter 2 (GLUT2) was assessed using
      Xenopus oocytes. Renal sodium-phosphate cotransporter 2a and 2c (Npt2a and Npt2c)
      expressions were evaluated in transgenically rescued Glut2-null mice (tgGlut2-/
      ). RESULTS: In both families, genetic mapping and sequence analysis of candidate
      genes led to the identification of two novel homozygous mutations (IVS4-2A>G and
      R124S, respectively) in GLUT2, the gene mutated in Fanconi-Bickel syndrome, a
      rare disease usually characterized by renal tubulopathy, impaired glucose
      homeostasis, and hepatomegaly. Xenopus oocytes expressing the [R124S]GLUT2 mutant
      showed a significant reduction in glucose transport, but neither wild-type nor
      mutant GLUT2 facilitated phosphate import or export; tgGlut2-/- mice demonstrated
      a profound reduction of Npt2c expression in the proximal renal tubules.
      CONCLUSIONS: Homozygous mutations in the facilitative glucose transporter GLUT2,
      which cause Fanconi-Bickel syndrome, can lead to very different clinical and
      biochemical findings that are not limited to mild proximal renal tubulopathy but
      can include significant hypercalciuria and highly variable degrees of urinary
      phosphate-wasting and hypophosphatemia, possibly because of the impaired proximal
      tubular expression of Npt2c.

PMID- 22865907
TI  - Somatic RAS mutations occur in a large proportion of sporadic RET-negative
      medullary thyroid carcinomas and extend to a previously unidentified exon.
AB  - CONTEXT: Medullary thyroid carcinoma (MTC) is characterized by proto-oncogene RET
      mutations in almost all hereditary cases as well as in more than 40% of sporadic
      cases. Recently, a high prevalence of RAS mutations was reported in sporadic MTC,
      suggesting an alternative genetic event in sporadic MTC tumorigenesis. OBJECTIVE:
      This study aimed to extend this observation by screening somatic mutational
      status of RET, BRAF, and the three RAS proto-oncogenes in a large series of
      patients with MTC. MATERIALS AND METHODS: Direct sequencing of RET (exons 8, 10,
      11, 13, 14, 15, 16), BRAF (exons 11 and 15), and KRAS, HRAS, and NRAS genes
      (exons 2, 3, and 4) was performed on DNA prepared from 50 MTC samples, including
      30 sporadic cases. RESULTS: Activating RET mutations were detected in the 20
      hereditary cases (germline mutations) and in 14 sporadic cases (somatic
      mutations). Among the 16 sporadic MTC without any RET mutation, eight H-RAS
      mutations and five K-RAS mutations were found. Interestingly, nine RAS mutations
      correspond to mutation hot spots in exons 2 and 3, but the other four mutations
      were detected in exon 4. The RET and RAS mutations were mutually exclusive. No
      RAS gene mutation was found in hereditary MTC, and no BRAF or NRAS mutation was
      observed in any of the 50 samples. CONCLUSIONS: Our study confirms that RAS
      mutations are frequent events in sporadic MTC. Moreover, we showed that RAS
      mutation analysis should not be limited to the classical mutational hot spots of
      RAS genes and should include analysis of exon 4.

PMID- 22865908
TI  - Supported liquid extraction offers improved sample preparation for aldosterone
      analysis by liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: To evaluate the accuracy and precision of a method for serum
      aldosterone using supported liquid extraction (SLE) for sample preparation
      instead of the more conventional liquid-liquid extraction (LLE) approach.
      METHODS: Two independently developed SLE-based LC-MS/MS methods for serum
      aldosterone (sample volumes 250 MUl and 300 MUl respectively) were compared to a
      modification of a previously reported LLE approach (sample volume 500 MUl) in two
      method comparisons (n=75 and n=97). SLE analyses were performed at two separate
      centres. Precision was evaluated at a single site using human pools in head-to
      head comparison between SLE and LLE. All analyses were performed on the ABSCIEX
      API-5000 LC-MS/MS system. RESULTS: At four increasing pool concentrations
      spanning 67-1060 pmol/l, total precision for SLE ranged from 6.8-4.1% compared
      with 11.1-4.3% for LLE. Differences did not reach statistical significance except
      at the lowest concentration where SLE was superior. Pasing Bablok regression
      comparisons were SLE=0.96*LLE-5.8 pmol/l (R(2)=0.985) and SLE=0.96*LLE-0.44
      pmol/l (R(2)=0.969). CONCLUSIONS: For analysis of serum aldosterone on the
      ABSCIEX API-5000, SLE affords a smaller sample volume while maintaining the
      accuracy and precision performance of LLE. By avoiding specimen vortexing, SLE
      also allows for greater automation in the sample preparation.

PMID- 22865909
TI  - Contribution of the different omega-3 fatty acid desaturase genes to the cold
      response in soybean.
AB  - This study analysed the contribution of each omega-3 desaturase to the cold
      response in soybean. Exposure to cold temperatures (5  degrees C) did not result
      in great modifications of the linolenic acid content in leaf membrane lipids.
      However, an increase in the GmFAD3A transcripts was observed both in plant leaves
      and soybean cells whereas no changes in GmFAD3B or GmFAD3C expression levels were
      detected. This increase was reversible and accompanied by the accumulation of an
      mRNA encoding a truncated form of GmFAD3A (GmFAD3A-T), which originated from
      alternative splicing of GmFAD3A in response to cold. When the expression of
      plastidial omega-3 desaturases was analysed, a transient accumulation of GmFAD7-2
      mRNA was detected upon cold exposure in mature soybean trifoliate leaves while
      GmFAD7-1 transcripts remained unchanged. No modification of the GmFAD8-1 and
      GmFAD8-2 transcripts was observed. The functionality of GmFAD3A, GmFAD3B, GmFAD3C
      and GmFAD3A-T was examined by heterologous expression in yeast. No activity was
      detected with GmFAD3A-T, consistent with the absence of one of the His boxes
      necessary for desaturase activity. The linolenic acid content of Sacharomyces
      cerevisiae cells overexpressing GmFAD3A or GmFAD3B was higher when the cultures
      were incubated at cooler temperatures, suggesting that reticular desaturases of
      the GmFAD3 family, and more specifically GmFAD3A, may play a role in the cold
      response, even in leaves. The data point to a regulatory mechanism of omega-3
      fatty acid desaturases in soybean affecting specific isoforms in both the plastid
      and the endoplasmic reticulum to maintain appropriate levels of linolenic acid
      under low temperature conditions.

PMID- 22865910
TI  - Gene duplication within the Green Lineage: the case of TEL genes.
AB  - Recent years have witnessed a breathtaking increase in the availability of genome
      sequence data, providing evidence of the highly duplicate nature of eukaryotic
      genomes. Plants are exceptional among eukaryotic organisms in that duplicate loci
      compose a large fraction of their genomes, partly because of the frequent
      occurrence of polyploidy (or whole-genome duplication) events. Tandem gene
      duplication and transposition have also contributed to the large number of
      duplicated genes in plant genomes. Evolutionary analyses allowed the dynamics of
      duplicate gene evolution to be studied and several models were proposed. It seems
      that, over time, many duplicated genes were lost and some of those that were
      retained gained new functions and/or expression patterns (neofunctionalization)
      or subdivided their functions and/or expression patterns between them
      (subfunctionalization). Recent studies have provided examples of genes that
      originated by duplication with successive diversification within plants. In this
      review, we focused on the TEL (TERMINAL EAR1-like) genes to illustrate such
      mechanisms. Emerged from the mei2 gene family, these TEL genes are likely to be
      land plant-specific. Phylogenetic analyses revealed one or two TEL copies per
      diploid genome. TEL gene degeneration and loss in several Angiosperm species such
      as in poplar and maize seem to have occurred. In Arabidopsis thaliana, whose
      genome experienced at least three polyploidy events followed by massive gene loss
      and genomic reorganization, two TEL genes were retained and two new shorter TEL
      like (MCT) genes emerged. Molecular and expression analyses suggest for these
      genes sub- and neofunctionalization events, but confirmation will come from their
      functional characterization.

PMID- 22865911
TI  - Roles and regulation of cytokinins in tomato fruit development.
AB  - Cytokinins (CKs) are thought to play important roles in fruit development,
      especially cell division. However, the mechanisms and regulation of CK activity
      have not been well investigated. This study analysed CK concentrations and
      expression of genes involved in CK metabolism in developing tomato (Solanum
      lycopersicum) ovaries. The concentrations of CK ribosides and isopentenyladenine
      and the transcript levels of the CK biosynthetic genes SlIPT3, SlIPT4, SlLOG6,
      and SlLOG8 were high at anthesis and decreased immediately afterward. In
      contrast, trans-zeatin concentration and the transcript levels of the CK
      biosynthetic genes SlIPT1, SlIPT2, SlCYP735A1, SlCYP735A2, and SlLOG2 increased
      after anthesis. The expression of type-A response regulator genes was high in
      tomato ovaries from pre-anthesis to early post-anthesis stages. These results
      suggest that the CK signal transduction pathway is active in the cell division
      phase of fruit development. This study also investigated the effect of CK
      application on fruit set and development. Application of a synthetic CK, N-(2
      chloro-pyridin-4-yl)-N'-phenylurea (CPPU), to unpollinated tomato ovaries induced
      parthenocarpic fruit development. The CPPU-induced parthenocarpic fruits were
      smaller than pollinated fruits, because of reduction of pericarp cell size rather
      than reduced cell number. Thus, CPPU-induced parthenocarpy was attributable to
      the promotion of cell division, not cell expansion. Overall, the results provide
      evidence that CKs are involved in cell division during development of tomato
      fruit.

PMID- 22865912
TI  - Nitric oxide-activated calcium/calmodulin-dependent protein kinase regulates the
      abscisic acid-induced antioxidant defence in maize.
AB  - Nitric oxide (NO), hydrogen peroxide (H2O2), and calcium (Ca2+)/calmodulin (CaM)
      are all required for abscisic acid (ABA)-induced antioxidant defence. Ca2+/CaM
      dependent protein kinase (CCaMK) is a strong candidate for the decoder of Ca2+
      signals. However, whether CCaMK is involved in ABA-induced antioxidant defence is
      unknown. The results of the present study show that exogenous and endogenous ABA
      induced increases in the activity of ZmCCaMK and the expression of ZmCCaMK in
      leaves of maize. Subcellular localization analysis showed that ZmCCaMK is located
      in the nucleus, the cytoplasm, and the plasma membrane. The transient expression
      of ZmCCaMK and the RNA interference (RNAi) silencing of ZmCCaMK analysis in maize
      protoplasts revealed that ZmCCaMK is required for ABA-induced antioxidant
      defence. Moreover, treatment with the NO donor sodium nitroprusside (SNP) induced
      the activation of ZmCCaMK and the expression of ZmCCaMK. Pre-treatments with an
      NO scavenger and inhibitor blocked the ABA-induced increases in the activity and
      the transcript level of ZmCCaMK. Conversely, RNAi silencing of ZmCCaMK in maize
      protoplasts did not affect the ABA-induced NO production, which was further
      confirmed using a mutant of OsCCaMK, the homologous gene of ZmCCaMK in rice.
      Moreover, H2O2 was also required for the ABA activation of ZmCCaMK, and pre
      treatments with an NO scavenger and inhibitor inhibited the H2O2-induced increase
      in the activity of ZmCCaMK. Taken together, the data clearly suggest that ZmCCaMK
      is required for ABA-induced antioxidant defence, and H2O2-dependent NO production
      plays an important role in the ABA-induced activation of ZmCCaMK.

PMID- 22865913
TI  - Polyphenol oxidases in Physcomitrella: functional PPO1 knockout modulates
      cytokinin-dependent development in the moss Physcomitrella patens.
AB  - Polyphenol oxidases (PPOs) are copper-binding enzymes of the plant secondary
      metabolism that oxidize polyphenols to quinones. Although PPOs are nearly
      ubiquitous in seed plants, knowledge on their evolution and function in other
      plant groups is missing. This study reports on the PPO gene family in the moss
      Physcomitrella patens (Hedw.) B.S.G. asan example for an early divergent plant.
      The P. patens PPO multigene family comprises 13 paralogues. Phylogenetic analyses
      suggest that plant PPOs evolved with the colonization of land and that PPO
      duplications within the monophyletic P. patens paralogue clade occurred after the
      separation of the moss and seed plant lineages. PPO functionality was
      demonstrated for recombinant PPO6. P. patens was analysed for phenolic compounds
      and six substances were detected intracellularly by LC-MS analysis: 4
      hydroxybenzoic acid, p-cumaric acid, protocatechuic acid, salicylic acid, caffeic
      acid, and an ester of caffeic acid. Targeted PPO1 knockout (d|ppo1) plants were
      generated and plants lacking PPO1 exhibited only ~30% of the wild-type PPO
      activity in the culture medium, thus suggesting extracellular localization of
      PPO1, which is in contrast to the mostly plastidic PPO localization in seed
      plants. Further, d|ppo1 lines formed significantly more gametophores with a
      reduced areal plant size, which could be related to an increase of endogenously
      produced cytokinins and indicates an impact of PPO1 on plant development. d|ppo1
      plants were less tolerant towards applied 4-methylcatechol compared to the wild
      type, which suggests a role of extracellular PPO1 in establishing appropriate
      conditions by the removal of inhibitory extracellular phenolic compounds.

PMID- 22865914
TI  - Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus
      infection.
AB  - Human CMV establishes lifelong persistence after primary infection. Chronic CMV
      infection is associated with intermittent viral reactivation inducing high
      frequencies of CD4+ T lymphocytes with potent antiviral and helper properties.
      Primary CMV infection is characterized by an intense viral replication lasting
      for several months. The impact of this prolonged exposure to high Ag loads on the
      functionality of CD4+ T cells remains incompletely understood. In pregnant women
      with primary CMV infection, we observed that CMV-specific CD4+ T lymphocytes had
      a decreased capacity to proliferate and to produce IL-2. A very large proportion
      of CMV-specific CD4+ T cells had downregulated the expression of CD28, a
      costimulatory molecule centrally involved in the production of IL-2.
      Unexpectedly, both CD28+ and CD28+ CD4+ T cells produced low levels of IL-2. This
      defective production of IL-2 was part of a larger downregulation of cytokine
      production. Indeed, CMV-specific CD4+ T cells produced lower amounts of IFN-gamma
      and TNF-alpha and showed lower functional avidity during primary as compared with
      chronic infection. Increased programmed death-1 expression was observed in CD28+
      CMV-specific CD4+ T cells, and programmed death-1 inhibition increased
      proliferative responses. These results indicate that primary CMV infection is
      associated with the exhaustion of CMV-specific CD4+ T cells displaying low
      functional avidity for viral Ags.

PMID- 22865915
TI  - Cutting edge: IL-10-mediated tristetraprolin induction is part of a feedback loop
      that controls macrophage STAT3 activation and cytokine production.
AB  - In activated macrophages, the anti-inflammatory cytokine IL-10 inhibits
      expression of molecules that propagate inflammation in a manner that depends on
      transcription factor STAT3. Expression of IL-10 is regulated
      posttranscriptionally by the RNA-binding protein tristetraprolin (TTP), which
      destabilizes IL-10 mRNA in activated macrophages. Using LPS-activated bone marrow
      derived murine macrophages, we demonstrate that TTP is a negative regulator of
      the IL-10/STAT3 anti-inflammatory response. LPS-stimulated TTP-deficient
      macrophages overproduced IL-10, contained increased amounts of activated STAT3,
      and showed reduced expression of inflammatory cytokines, including cytokines
      encoded by TTP target mRNAs. Thus, in LPS-stimulated TTP-deficient macrophages,
      increased IL-10/STAT3 anti-inflammatory control was dominant over the mRNA
      stabilization of specific TTP targets. The TTP gene promoter contains a conserved
      STAT3 binding site, and IL-10 induces STAT3 recruitment to this site.
      Correspondingly, STAT3 was required for efficient IL-10-induced TTP expression.
      Hence, by inducing TTP expression, STAT3 activates a negative regulatory loop
      that controls the IL-10/STAT3 anti-inflammatory response.

PMID- 22865916
TI  - Noncovalent assembly of anti-dendritic cell antibodies and antigens for evoking
      immune responses in vitro and in vivo.
AB  - Targeting of Ags directly to dendritic cells (DCs) through anti-DC receptor Ab
      fused to Ag proteins is a promising approach to vaccine development. However, not
      all Ags can be expressed as a rAb directly fused to a protein Ag. In this study,
      we show that noncovalent assembly of Ab-Ag complexes, mediated by interaction
      between dockerin and cohesin domains from cellulose-degrading bacteria, can
      greatly expand the range of Ags for this DC-targeting vaccine technology. rAbs
      with a dockerin domain fused to the rAb H chain C terminus are efficiently
      secreted by mammalian cells, and many Ags not secreted as rAb fusion proteins are
      readily expressed as cohesin directly fused to Ag either via secretion from
      mammalian cells or as soluble cytoplasmic Escherichia coli products. These form
      very stable and homogeneous complexes with rAb fused to dockerin. In vitro, these
      complexes can efficiently bind to human DC receptors followed by presentation to
      Ag-specific CD4+ and CD8+ T cells. Low doses of the HA1 subunit of influenza
      hemagglutinin conjugated through this means to anti-Langerin rAbs elicited Flu
      HA1-specific Ab and T cell responses in mice. Thus, the noncovalent assembly of
      rAb and Ag through dockerin and cohesin interaction provides a useful modular
      strategy for development and testing of prototype vaccines for elicitation of Ag
      specific T and B cell responses, particularly when direct rAb fusions to Ag
      cannot be expressed.

PMID- 22865917
TI  - Shaping of human germline IgH repertoires revealed by deep sequencing.
AB  - To understand better how selection processes balance the benefits of Ig
      repertoire diversity with the risks of autoreactivity and nonfunctionality of
      highly variable IgH CDR3s, we collected millions of rearranged germline IgH CDR3
      sequences by deep sequencing of DNA from mature human naive B cells purified from
      four individuals and analyzed the data with computational methods. Long HCDR3
      regions, often components of HIV-neutralizing Abs, appear to derive not only from
      incorporation of long D genes and insertion of large N regions but also by usage
      of multiple D gene segments in tandem. However, comparison of productive and out
      of-frame IgH rearrangements revealed a selection bias against long HCDR3 loops,
      suggesting these may be disproportionately either poorly functional or
      autoreactive. Our data suggest that developmental selection removes HCDR3 loops
      containing patches of hydrophobicity, which are commonly found in some auto
      antibodies, and at least 69% of the initial productive IgH rearrangements are
      removed from the repertoire during B cell development. Additionally, we have
      demonstrated the potential utility of this new technology for vaccine development
      with the identification in all four individuals of related candidate germline IgH
      precursors of the HIV-neutralizing Ab 4E10.

PMID- 22865918
TI  - Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of
      intestinal absorption of 4-HHE and reactivity in intestinal cells.
AB  - Dietary intake of long-chain n-3 PUFA is now widely advised for public health and
      in medical practice. However, PUFA are highly prone to oxidation, producing
      potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming
      oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly
      described. We therefore studied such effects and hypothesized the involvement of
      the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA
      end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets
      containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally
      administered 4-HHE and euthanized postprandially versus baseline mice. In vitro,
      human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals.
      Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01)
      compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory
      markers and activation of nuclear factor kappaB (NF-kappaB) in the small
      intestine along with decreasing Paneth cell number (up to -19% in the duodenum).
      Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with
      formation of 4-HHE-protein adducts and increased expression of glutathione
      peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of
      oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal
      absorption and triggers oxidative stress and inflammation in the upper intestine.

PMID- 22865919
TI  - Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope
      in Saccharomyces cerevisiae.
AB  - Post-translational modification of proteins by lysine acetylation plays important
      regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a
      widely used unicellular eukaryotic model organism in biomedical research. S.
      cerevisiae contains several evolutionary conserved lysine acetyltransferases and
      deacetylases. However, only a few dozen acetylation sites in S. cerevisiae are
      known, presenting a major obstacle for further understanding the regulatory roles
      of acetylation in this organism. Here we use high resolution mass spectrometry to
      identify about 4000 lysine acetylation sites in S. cerevisiae. Acetylated
      proteins are implicated in the regulation of diverse cytoplasmic and nuclear
      processes including chromatin organization, mitochondrial metabolism, and protein
      synthesis. Bioinformatic analysis of yeast acetylation sites shows that
      acetylated lysines are significantly more conserved compared with nonacetylated
      lysines. A large fraction of the conserved acetylation sites are present on
      proteins involved in cellular metabolism, protein synthesis, and protein folding.
      Furthermore, quantification of the Rpd3-regulated acetylation sites identified
      several previously known, as well as new putative substrates of this deacetylase.
      Rpd3 deficiency increased acetylation of the SAGA (Spt-Ada-Gcn5
      Acetyltransferase) complex subunit Sgf73 on K33. This acetylation site is located
      within a critical regulatory domain in Sgf73 that interacts with Ubp8 and is
      involved in the activation of the Ubp8-containing histone H2B deubiquitylase
      complex. Our data provides the first global survey of acetylation in budding
      yeast, and suggests a wide-ranging regulatory scope of this modification. The
      provided dataset may serve as an important resource for the functional analysis
      of lysine acetylation in eukaryotes.

PMID- 22865920
TI  - Aurora B-dependent regulation of class IIa histone deacetylases by mitotic
      nuclear localization signal phosphorylation.
AB  - Class IIa histone deacetylases (HDACs 4/5/7/9) are transcriptional regulators
      with critical roles in cardiac disease and cancer. HDAC inhibitors are promising
      anticancer agents, and although they are known to disrupt mitotic progression,
      the underlying mechanisms of mitotic regulation by HDACs are not fully
      understood. Here we provide the first identification of histone deacetylases as
      substrates of Aurora B kinase (AurB). Our study identifies class IIa HDACs as a
      novel family of AurB targets and provides the first evidence that HDACs are
      temporally and spatially regulated by phosphorylation during the cell cycle. We
      define the precise site of AurB-mediated phosphorylation as a conserved serine
      within the nuclear localization signals of HDAC4, HDAC5, and HDAC9 at Ser265,
      Ser278, and Ser242, respectively. We establish that AurB interacts with these
      HDACs in vivo, and that this association increases upon disruption of 14-3-3
      binding. We observe colocalization of endogenous, phosphorylated HDACs with AurB
      at the mitotic midzone in late anaphase and the midbody during cytokinesis,
      complemented by a reduction in HDAC interactions with components of the nuclear
      corepressor complex. We propose that AurB-dependent phosphorylation of HDACs
      induces sequestration within a phosphorylation gradient at the midzone,
      maintaining separation from re-forming nuclei and contributing to transcriptional
      control.

PMID- 22865921
TI  - Inference and validation of protein identifications.
AB  - Discovery or shotgun proteomics has emerged as the most powerful technique to
      comprehensively map out a proteome. Reconstruction of protein identities from the
      raw mass spectrometric data constitutes a cornerstone of any shotgun proteomics
      workflow. The inherent uncertainty of mass spectrometric data and the complexity
      of a proteome render protein inference and the statistical validation of protein
      identifications a non-trivial task, still being a subject of ongoing research.
      This review aims to survey the different conceptual approaches to the different
      tasks of inferring and statistically validating protein identifications and to
      discuss their implications on the scope of proteome exploration.

PMID- 22865922
TI  - Topograph, a software platform for precursor enrichment corrected global protein
      turnover measurements.
AB  - Defects in protein turnover have been implicated in a broad range of diseases,
      but current proteomics methods of measuring protein turnover are limited by the
      software tools available. Conventional methods require indirect approaches to
      differentiate newly synthesized protein when synthesized from partially labeled
      precursor pools. To address this, we have developed Topograph, a software
      platform which calculates the fraction of peptides that are from newly
      synthesized proteins and their turnover rates. A unique feature of Topograph is
      the ability to calculate amino acid precursor pool enrichment levels which allows
      for accurate calculations when the precursor pool is not fully labeled, and the
      approach used by Topograph is applicable regardless of the stable isotope label
      used. We validate the Topograph algorithms using data acquired from a mouse
      labeling experiment and demonstrate the influence that precursor pool corrections
      can have on protein turnover measurements.

PMID- 22865923
TI  - A method for large-scale identification of protein arginine methylation.
AB  - The lack of methods for proteome-scale detection of arginine methylation
      restricts our knowledge of its relevance in physiological and pathological
      processes. Here we show that most tryptic peptides containing methylated
      arginine(s) are highly basic and hydrophilic. Consequently, they could be
      considerably enriched from total cell extracts by simple protocols using either
      one of strong cation exchange chromatography, isoelectric focusing, or
      hydrophilic interaction liquid chromatography, the latter being by far the most
      effective of all. These methods, coupled with heavy methyl-stable isotope
      labeling by amino acids in cell culture and mass spectrometry, enabled in T cells
      the identification of 249 arginine methylation sites in 131 proteins, including
      190 new sites and 93 proteins not previously known to be arginine methylated. By
      extending considerably the number of known arginine methylation sites, our data
      reveal a novel proline-rich consensus motif and identify for the first time
      arginine methylation in proteins involved in cytoskeleton rearrangement at the
      immunological synapse and in endosomal trafficking.

PMID- 22865924
TI  - Parallel reaction monitoring for high resolution and high mass accuracy
      quantitative, targeted proteomics.
AB  - Selected reaction monitoring on a triple quadrupole mass spectrometer is
      currently experiencing a renaissance within the proteomics community for its, as
      yet, unparalleled ability to characterize and quantify a set of proteins
      reproducibly, completely, and with high sensitivity. Given the immense benefit
      that high resolution and accurate mass instruments have brought to the discovery
      proteomics field, we wondered if highly accurate mass measurement capabilities
      could be leveraged to provide benefits in the targeted proteomics domain as well.
      Here, we propose a new targeted proteomics paradigm centered on the use of next
      generation, quadrupole-equipped high resolution and accurate mass instruments:
      parallel reaction monitoring (PRM). In PRM, the third quadrupole of a triple
      quadrupole is substituted with a high resolution and accurate mass mass analyzer
      to permit the parallel detection of all target product ions in one, concerted
      high resolution mass analysis. We detail the analytical performance of the PRM
      method, using a quadrupole-equipped bench-top Orbitrap MS, and draw a performance
      comparison to selected reaction monitoring in terms of run-to-run
      reproducibility, dynamic range, and measurement accuracy. In addition to
      requiring minimal upfront method development and facilitating automated data
      analysis, PRM yielded quantitative data over a wider dynamic range than selected
      reaction monitoring in the presence of a yeast background matrix because of PRM's
      high selectivity in the mass-to-charge domain. With achievable linearity over the
      quantifiable dynamic range found to be statistically equal between the two
      methods, our investigation suggests that PRM will be a promising new addition to
      the quantitative proteomics toolbox.

PMID- 22865925
TI  - Is mandatory research ethics reviewing ethical?
AB  - Review boards responsible for vetting the ethical conduct of research have been
      criticised for their costliness, unreliability and inappropriate standards when
      evaluating some non-medical research, but the basic value of mandatory ethical
      review has not been questioned. When the standards that review boards use to
      evaluate research proposals are applied to review board practices, it is clear
      that review boards do not respect researchers or each other, lack merit and
      integrity, are not just and are not beneficent. The few benefits of mandatory
      ethical review come at a much greater, but mainly hidden, social cost. It is time
      that responsibility for the ethical conduct of research is clearly transferred to
      researchers, except possibly in that small proportion of cases where prospective
      research participants may be so intrinsically vulnerable that their well-being
      may need to be overseen. 

PMID- 22865926
TI  - Honorary authorship epidemic in scholarly publications? How the current use of
      citation-based evaluative metrics make (pseudo)honorary authors from honest
      contributors of every multi-author article.
AB  - The current use of citation-based metrics to evaluate the research output of
      individual researchers is highly discriminatory because they are uniformly
      applied to authors of single-author articles as well as contributors of multi
      author papers. In the latter case, these quantitative measures are counted, as if
      each contributor were the single author of the full article. In this way, each
      and every contributor is assigned the full impact-factor score and all the
      citations that the article has received. This has a multiplication effect on each
      contributor's citation-based evaluative metrics of multi-author articles, because
      the more contributors an article has, the more undeserved credit is assigned to
      each of them. In this paper, I argue that this unfair system could be made fairer
      by requesting the contributors of multi-author articles to describe the nature of
      their contribution, and to assign a numerical value to their degree of relative
      contribution. In this way, we could create a contribution-specific index of each
      contributor for each citation metric. This would be a strong disincentive against
      honorary authorship and publication cartels, because it would transform the
      current win-win strategy of accepting honorary authors in the byline into a zero
      sum game for each contributor. 

PMID- 22865927
TI  - Reconciling informed consent with prescription drug requirements.

PMID- 22865928
TI  - Tryptamine serves as a proligand of the AhR transcriptional pathway whose
      activation is dependent of monoamine oxidases.
AB  - The function of the aryl hydrocarbon receptor (AhR) in mediating the biological
      effect to environmental pollutants is well established. However, accumulated
      evidence indicates a wide range of physiological and pathological functions
      mediated by the AhR, suggesting the existence of endogenous AhR ligand(s). The
      nature of an AhR ligand remain elusive; however, it is known that the AhR is
      activated by several compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin or
      the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. In this study, we
      show that physiological concentrations of tryptamine (TA) lead to induction of
      cytochrome P4501A1 transcription through an AhR-dependent mechanism. In addition,
      we show that activation of the AhR by TA requires a functional monoamino oxidase
      system, suggesting that TA acts as an AhR proligand possibly by converting to a
      high-affinity AhR ligand. Taken together, we show a possible mechanism, through
      which AhR signaling is activated by endogenous conversion of TA involving
      monoamine oxidases.

PMID- 22865929
TI  - ERalpha phosphorylation at Y537 by Src triggers E6-AP-ERalpha binding, ERalpha
      ubiquitylation, promoter occupancy, and target gene expression.
AB  - Many transcription factors undergo transcription-coupled proteolysis. Although
      ligand binding activates ubiquitin proteolysis of estrogen receptor alpha
      (ERalpha), mechanisms governing this and its relationship to transcriptional
      activation were unclear. Data presented link cross talk between the Src kinase
      and liganded ERalpha with ERalpha activation and its ubiquitylation. Liganded
      ERalpha rapidly activates and recruits Src, which phosphorylates ERalpha at
      tyrosine 537 (Y537). This enhances ERalpha binding to the ubiquitin
      ligase/ERalpha coactivator, E6-associated protein (E6-AP), stimulating ERalpha
      ubiquitylation, target gene activation, and ultimately ERalpha loss. ERalpha
      phosphorylation by Src promotes ERalpha ubiquitylation by E6-AP and proteasomal
      degradation in vitro. Src inhibition impairs estrogen (E2)-activated ERalpha:E6
      AP binding, reducing ERalpha degradation. ERalpha-Y537F shows little E2
      stimulated degradation and activates native ERalpha target genes poorly. Src
      activation enhances ERalpha and E6-AP binding and their occupancy at ERalpha
      target gene promoters to enhance transcription. Thus, ERalphaY537 phosphorylation
      drives ERalpha:E6-AP binding to at least a subset of target promoters, linking
      transcriptional activation to ERalpha degradation and providing a novel mechanism
      to fine tune ERalpha action. The observation that ERalpha transcriptional
      activity can be briskly maintained in a context of reduced ERalpha levels raises
      the possibility that hormonally sensitive tissues may not always show robust
      ERalpha protein levels.

PMID- 22865930
TI  - Focused high frequency needle transducer for ultrasonic imaging and trapping.
AB  - A miniature focused needle transducer (<1 mm) was fabricated using the press
      focusing technique. The measured pulse-echo waveform showed the transducer had
      center frequency of 57.5 MHz with 54% bandwidth and 14 dB insertion loss. To
      evaluate the performance of this type of transducer, invitro ultrasonic
      biomicroscopy imaging on the rabbit eye was obtained. Moreover, a single beam
      acoustic trapping experiment was performed using this transducer. Trapping of
      targeted particle size smaller than the ultrasonic wavelength was observed.
      Potential applications of these devices include minimally invasive measurements
      of retinal blood flow and single beam acoustic trapping of microparticles.

PMID- 22865931
TI  - Adaptive System Identification for Estimating Future Glucose Concentrations and
      Hypoglycemia Alarms.
AB  - Many patients with diabetes experience high variability in glucose concentrations
      that includes prolonged hyperglycemia or hypoglycemia. Models predicting a
      subject's future glucose concentrations can be used for preventing such
      conditions by providing early alarms. This paper presents a time-series model
      that captures dynamical changes in the glucose metabolism. Adaptive system
      identification is proposed to estimate model parameters which enable the
      adaptation of the model to inter-/intra-subject variation and glycemic
      disturbances. It consists of online parameter identification using the weighted
      recursive least squares method and a change detection strategy that monitors
      variation in model parameters. Univariate models developed from a subject's
      continuous glucose measurements are compared to multivariate models that are
      enhanced with continuous metabolic, physical activity and lifestyle information
      from a multi-sensor body monitor. A real life application for the proposed
      algorithm is demonstrated on early (30 min in advance) hypoglycemia detection.

PMID- 22865932
TI  - Propensity for Violence among Homeless and Runaway Adolescents: An Event History
      Analysis*
AB  - Little is known about the prevalence of violent behaviors among homeless and
      runaway adolescents or the specific behavioral factors that influence violent
      behaviors across time. In this longitudinal study of 300 homeless and runaway
      adolescents aged 16-19 years at baseline, we use event history analysis to assess
      the factors associated with acts of violence over three years, controlling for
      individual propensities and time-varying behaviors. The results indicate that
      females, non-minorities, and non-heterosexuals were less likely to engage in
      violence across time. Those who met criteria for substance abuse disorders (i.e.
      alcohol abuse, alcohol dependence, drug abuse) were more likely to engage in
      violence. A history of caretaker abuse was associated with violent behaviors, as
      were street survival strategies such as selling drugs, participating in gang
      activity, and associating with deviant peers. Simply having spent time directly
      on the streets at any specific time point also increased the likelihood for
      violence.

PMID- 22865933
TI  - Nanofluidic preconcentration and detection of nanoparticles.
AB  - The fast detection and characterization of nanoparticles, such as viruses or
      environmental pollutants, are important in fields ranging from biosensing to
      quality control. However, most existing techniques have practical throughput
      limitations, which significantly limit their applicability to low analyte
      concentrations. Here, we present an integrated nanofluidic scheme for
      preconcentration and subsequent detection of nanoparticle samples within a
      continuous flow-through system. Using a Brownian ratchet mechanism, we increase
      the nanoparticle concentration ~27-fold. Single nanoparticles are subsequently
      detected and characterized by optical heterodyne interferometry. A wide range of
      potential applications can be foreseen, including real-time analysis of
      clinically relevant virus samples and contamination control of processing fluids
      used in the semiconductor industry.

PMID- 22865934
TI  - The Reactivity of Polymersome Encapsulated Hemoglobin with Physiologically
      Important Gaseous Ligands: Oxygen, Carbon Monoxide and Nitric Oxide.
AB  - Two distinct preparations of amphiphilic diblock copolymer vesicles (i.e.
      polymersomes), composed of (poly(ethylene oxide)-poly(butadiene)) (PEO-PBD), with
      molecular weights of 1.8 kDa and 10.4 kDa, offering different hydrophobic
      membrane thicknesses, were used to encapsulate the oxygen (O(2)) storage and
      transport protein hemoglobin (Hb) for possible application as a red blood cell
      (RBC) substitute. Key biophysical properties as well as the kinetics of
      polymersome encapsulated Hb (PEH) interaction with physiologically important
      gaseous ligands (O(2), carbon monoxide and nitric oxide) were measured as a
      function of the hydrophobic membrane thickness of the PEH particle. Taken
      together, the results of this work show that PEHs exhibit biophysical properties
      and retarded ligand binding/release kinetics (compared to cell-free Hb), which
      are similar to the behavior of RBCs. Therefore, PEHs have the potential to serve
      as safe and efficacious RBC substitutes for use in transfusion medicine.

PMID- 22865935
TI  - A hybrid formalism combining fluctuating hydrodynamics and generalized Langevin
      dynamics for the simulation of nanoparticle thermal motion in an incompressible
      fluid medium.
AB  - A novel hybrid scheme based on Markovian fluctuating hydrodynamics of the fluid
      and a non-Markovian Langevin dynamics with the Ornstein-Uhlenbeck noise
      perturbing the translational and rotational equations of motion of the
      nanoparticle is employed to study the thermal motion of a nanoparticle in an
      incompressible Newtonian fluid medium. A direct numerical simulation adopting an
      arbitrary Lagrangian-Eulerian (ALE) based finite element method (FEM) is employed
      in simulating the thermal motion of a particle suspended in the fluid confined in
      a cylindrical vessel. The results for thermal equilibrium between the particle
      and the fluid are validated by comparing the numerically predicted temperature of
      the nanoparticle with that obtained from the equipartition theorem. The nature of
      the hydrodynamic interactions is verified by comparing the velocity
      autocorrelation function (VACF) and mean squared displacement (MSD) with well
      known analytical results. For nanoparticle motion in an incompressible fluid, the
      fluctuating hydrodynamics approach resolves the hydrodynamics correctly but does
      not impose the correct equipartition of energy based on the nanoparticle mass
      because of the added mass of the displaced fluid. In contrast, the Langevin
      approach with an appropriate memory is able to show the correct equipartition of
      energy, but not the correct short- and long-time hydrodynamic correlations. Using
      our hybrid approach presented here, we show for the first time, that we can
      simultaneously satisfy the equipartition theorem and the (short- and long-time)
      hydrodynamic correlations. In effect, this results in a thermostat that also
      simultaneously preserves the true hydrodynamic correlations. The significance of
      this result is that our new algorithm provides a robust computational approach to
      explore nanoparticle motion in arbitrary geometries and flow fields, while
      simultaneously enabling us to study carrier adhesion mediated by biological
      reactions (receptor-ligand interactions) at the vessel wall at a specified finite
      temperature.

PMID- 22865936
TI  - A field method to store samples from temperate mountain grassland soils for
      analysis of phospholipid fatty acids.
AB  - The storage of soil samples for PLFA analysis can lead to shifts in the microbial
      community composition. We show here that conserving samples in RNAlater, which is
      already widely used to store samples for DNA and RNA analysis, proved to be as
      sufficient as freezing at -20  degrees C and preferable over storage at 4 
      degrees C for temperate mountain grassland soil. The total amount of extracted
      PLFAs was not changed by any storage treatment. Storage at 4  degrees C led to an
      alteration of seven out of thirty individual biomarkers, while freezing and
      storage in RNAlater caused changes in the amount of fungal biomarkers but had no
      effect on any other microbial group. We therefore suggest that RNAlater could be
      used to preserve soil samples for PLFA analysis when immediate extraction or
      freezing of samples is not possible, for example during sampling campaigns in
      remote areas or during transport and shipping.

PMID- 22865937
TI  - Synthesis of CJ-15,208, a novel kappa-opioid receptor antagonist.
AB  - The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a
      kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.; Kojima,
      Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N.
      J. Antibiot. (Tokyo)2002, 55, 847-854.], were synthesized to determine the
      tryptophan stereochemistry in the natural product. A strategy was developed to
      select linear precursor peptides that favor cyclization using molecular modeling,
      and optimized cyclization conditions are reported. The optical rotation of the l
      Trp isomer is consistent with that of the natural product. Unexpectedly both
      isomers exhibit similar nanomolar affinity for KOR.

PMID- 22865938
TI  - A Simple, General Synthesis of Carbonimidic Dichlorides.
AB  - The reaction of aliphatic and aromatic isonitriles with sulfuryl chloride
      provides an efficient, general route to the corresponding dichlorides without
      byproducts of free-radical substitution.

PMID- 22865939
TI  - Biodegradation of Toluene Under Seasonal and Diurnal Fluctuations of Soil-Water
      Temperature.
AB  - An increasing interest in bioremediation of hydrocarbon polluted sites raises the
      question of the influence of seasonal and diurnal changes on soil-water
      temperature on biodegradation of BTEX, a widespread group of (sub)-surface
      contaminants. Therefore, we investigated the impact of a wide range of varying
      soil-water temperature on biodegradation of toluene under aerobic conditions. To
      see the seasonal impact of temperature, three sets of batch experiments were
      conducted at three different constant temperatures: 10 degrees C, 21 degrees C,
      and 30 degrees C. These conditions were considered to represent (1) winter, (2)
      spring and/or autumn, and (3) summer seasons, respectively, at many polluted
      sites. Three additional sets of batch experiments were performed under
      fluctuating soil-water temperature cases (21<>10 degrees C, 30<>21 degrees C, and
      10<>30 degrees C) to mimic the day-night temperature patterns expected during the
      year. The batches were put at two different temperatures alternatively to
      represent the day (high-temperature) and night (low-temperature) times. The
      results of constant- and fluctuating-temperature experiments show that toluene
      degradation is strongly dependent on soil-water temperature level. An almost two
      fold increase in toluene degradation time was observed for every 10 degrees C
      decrease in temperature for constant-temperature cases. Under fluctuating
      temperature conditions, toluene degraders were able to overcome the temperature
      stress and continued thriving during all considered weather scenarios. However, a
      slightly longer time was taken compared to the corresponding time at daily mean
      temperature conditions. The findings of this study are directly useful for
      bioremediation of hydrocarbon-polluted sites having significant diurnal and
      seasonal variations of soil-water temperature.

PMID- 22865940
TI  - Culture-Dependent and Culture-Independent Methods in Evaluation of Emission of
      Enterobacteriaceae from Sewage to the Air and Surface Water.
AB  - The number of Enterobacteriaceae, with particular attention given to the presence
      of Escherichia coli and Klebsiella pneumoniae, was determined in hospital
      effluents and municipal wastewater after various stages of purification. The
      emission of these microorganisms to the ambient air near wastewater treatment
      plant (WWTP) facilities and to the river water, which is a receiver of the WWTP
      effluent, was also studied using fluorescence in situ hybridization (FISH) and
      cultivation methods. The number of Enterobacteriaceae determined by cultivation
      and fluorescence methods in different kinds of sewage sample ranged from 0.5 *
      10(3) to 2.9 * 10(6) CFU/ml and from 2.2 * 10(5) to 1.3 * 10(8) cells/ml,
      respectively. Their removal rates during treatment processes were close to 99 %,
      but the number of these bacteria in the WWTP outflow was quite high and ranged
      from 5.9 * 10(3) to 3.5 * 10(4) CFU/ml and from 1.1 * 10(5) to 6.1 * 10(5)
      cells/ml, respectively. In the river water and the air samples, the number of
      Enterobacteriaceae was also high and ranged from 4.1 * 10(3) to 7.9 * 10(3)
      CFU/ml and from 3 to 458 CFU/m(3), respectively. The numbers of these
      microorganisms obtained from fluorescence and cultivation methods were
      statistically and significantly correlated; however, the analysis of the studied
      samples indicated that the FISH method gave values up to 10(3)-fold times greater
      than those obtained by the cultivation method. From a sanitary point of view,
      this means that the number of viable fecal bacteria is systematically
      underestimated by traditional culture-based methods. Thus, the FISH proves to be
      a method that could be used to estimate bacterial load, particularly in air
      samples and less contaminated river water.

PMID- 22865941
TI  - Rhamnolipids Increase the Phytotoxicity of Diesel Oil Towards Four Common Plant
      Species in a Terrestrial Environment.
AB  - The study focused on assessing the influence of rhamnolipids on the phytotoxicity
      of diesel oil-contaminated soil samples. Tests evaluating the seed germination
      and growth inhibition of four terrestrial plant species (alfalfa, sorghum,
      mustard and cuckooflower) were carried out at different rhamnolipid
      concentrations (ranging from 0 to 1.200 mg/kg of wet soil). The experiments were
      performed in soil samples with a different diesel oil content (ranging from 0 to
      25 ml/kg of wet soil). It was observed that the sole presence of rhamnolipids may
      be phytotoxic at various levels, which is especially notable for sorghum (the
      germination index decreased to 41 %). The addition of rhamnolipids to diesel oil
      contaminated soil samples contributed to a significant increase of their
      phytotoxicity. The most toxic effect was observed after a rhamnolipid
      supplemented diesel oil biodegradation, carried out with the use of a hydrocarbon
      degrading bacteria consortium. The supplemention of rhamnolipids (600 mg/kg of
      wet soil) resulted in a decrease of seed germination of all studied plant species
      and an inhibition of microbial activity, which was measured by the 2,3,5
      triphenyltetrazolium chloride tests. These findings indicate that the presence of
      rhamnolipids may considerably increase the phytotoxicity of diesel oil.
      Therefore, their use at high concentrations, during in situ bioremediation
      processes, should be avoided in a terrestrial environment.

PMID- 22865942
TI  - Atmospheric Ionic Deposition in Tropical Sites of Central Sulawesi Determined by
      Ion Exchange Resin Collectors and Bulk Water Collector.
AB  - In the light of global change, the necessity to monitor atmospheric depositions
      that have relevant effects on ecosystems is ever increasing particularly for
      tropical sites. For this study, atmospheric ionic depositions were measured on
      tropical Central Sulawesi at remote sites with both a conventional bulk water
      collector system (BWS collector) and with a passive ion exchange resin collector
      system (IER collector). The principle of IER collector to fix all ionic
      depositions, i.e. anions and cations, has certain advantages referring to (1)
      post-deposition transformation processes, (2) low ionic concentrations and (3)
      low rainfall and associated particulate inputs, e.g. dust or sand. The ionic
      concentrations to be measured for BWS collectors may easily fall below detection
      limits under low deposition conditions which are common for tropical sites of low
      land use intensity. Additionally, BWS collections are not as independent from the
      amount of rain fallen as are IER collections. For this study, the significant
      differences between both collectors found for nearly all measured elements were
      partly correlated to the rainfall pattern, i.e. for calcium, magnesium, potassium
      and sodium. However, the significant differences were, in most cases, not highly
      relevant. More relevant differences between the systems were found for aluminium
      and nitrate (434-484 %). Almost five times higher values for nitrate clarified
      the advantage of the IER system particularly for low deposition rate which is one
      particularity of atmospheric ionic deposition in tropical sites of extensive land
      use. The monthly resolution of the IER data offers new insights into the temporal
      distribution of annual ionic depositions. Here, it did not follow the tropical
      rain pattern of a drier season within generally wet conditions.

PMID- 22865943
TI  - Responding to Anxiety with Rumination and Hopelessness: Mechanism of Anxiety
      Depression Symptom Co-Occurrence?
AB  - The current research proposes that certain anxiety response styles (specifically,
      responding to anxiety symptoms with rumination or hopeless cognitions) may
      increase risk of depressive symptoms, contributing to anxiety-depression
      comorbidity. We delineate preliminary evidence for this model in three studies.
      In Study 1, controlling for anxiety response styles significantly reduced the
      association between anxiety and depressive symptoms in an undergraduate sample.
      In Study 2, these findings were replicated controlling for conceptually related
      variables, and anxiety interacted with anxiety response styles to predict greater
      depressive symptoms. In Study 3, anxiety response styles moderated the
      prospective association between anxiety and later depression in a generalized
      anxiety disorder sample. Results support a role for anxiety response styles in
      anxiety-depression co-occurrence, and show that hopeless/ruminative anxiety
      response styles can be measured with high reliability and convergent and
      divergent validity.

PMID- 22865944
TI  - Semiparametric Efficient Estimation for a Class of Generalized Proportional Odds
      Cure Models.
AB  - We present a mixture cure model with the survival time of the "uncured" group
      coming from a class of linear transformation models, which is an extension of the
      proportional odds model. This class of model, first proposed by Dabrowska and
      Doksum (1988), which we term "generalized proportional odds model," is well
      suited for the mixture cure model setting due to a clear separation between long
      term and short-term effects. A standard expectation-maximization algorithm can be
      employed to locate the nonparametric maximum likelihood estimators, which are
      shown to be consistent and semiparametric efficient. However, there are
      difficulties in the M-step due to the nonparametric component. We overcome these
      difficulties by proposing two different algorithms. The first is to employ an
      majorize-minimize (MM) algorithm in the M-step instead of the usual Newton
      Raphson method, and the other is based on an alternative form to express the
      model as a proportional hazards frailty model. The two new algorithms are
      compared in a simulation study with an existing estimating equation approach by
      Lu and Ying (2004). The MM algorithm provides both computational stability and
      efficiency. A case study of leukemia data is conducted to illustrate the proposed
      procedures.

PMID- 22865945
TI  - Territorial Polemics: A Response to Roberts.
AB  - Our recent paper Lledo-Ferrer et al. (International Journal of Primatology 32:
      974-991, 2011) questioned the classic view of territoriality and chemical
      communication in wild callitrichids, saddleback tamarins (Saguinus fuscicollis).
      We suggested that rather than defending a territory or resources, chemical
      communication was more likely to be a way of exchanging reproductive information
      between groups. Roberts (International Journal of Primatology 33, 2012).
      challenged this interpretation, considering that the results could more
      parsimoniously be interpreted as fulfilling a resource defense strategy. This
      response is intended to clarify some aspects of the debate and to suggest how
      further research could shed new light on the present polemics.

PMID- 22865946
TI  - "The Luggage that isn't Theirs is Too Heavy...":Understandings of Orphan
      Disadvantage in Lesotho.
AB  - In Southern Africa, high adult HIV prevalence has fueled concern about the
      welfare of children losing parents to the epidemic. A growing body of evidence
      indicates that parental, particularly maternal, death is negatively associated
      with child outcomes. However, a better understanding of the mechanisms is needed.
      In addition, the way orphan disadvantage and the mechanisms giving rise to it are
      understood on the ground is essential for the successful translation of research
      into policies and programs. This study employs data from 89 in-depth interviews
      with caregivers and key informants in Lesotho, a setting where approximately one
      quarter of adults is infected with HIV, to elaborate understandings of orphan
      disadvantage. Our analysis focuses on two questions: (i) Do local actors perceive
      orphans to be disadvantaged compared to non-orphans, and if so, in what ways; and
      (ii) How do they explain orphans' differential disadvantage?Analyses suggest that
      orphans were widely perceived to be disadvantaged; respondents described this
      disadvantage in material as well as affective domains. Thematic analyses reveal
      five broad categories of explanation: poverty, love and kin connection, caregiver
      character, perceptions of orphans, and community norms related to orphan care.
      These results underscore the need for research and policy to address (i) multiple
      types of disadvantage, including deficits in kindness and attention; and (ii) the
      social embeddedness of disadvantage, recognizing that poverty, kinship, and
      community interact with individual attributes to shape caregiving relationships
      and child experiences. The findings suggest limited success for programs and
      policies that do not address the emotional needs of children, or that focus on
      child or caregiver support to the exclusion of community outreach.

PMID- 22865947
TI  - On the search of optimal reconstruction resolution.
AB  - In this paper we present a novel algorithm to optimize the reconstruction from
      non-uniform point sets. We introduce a statistically-derived topology-controller
      for selecting the reconstruction resolution of a given non-uniform point set.
      Deriving information from homology-based statistics, our topology-controller
      ensures a stable and sound basis for the analysis process. By analyzing our
      topology-controller, we select an optimal reconstruction resolution which ensures
      both low reconstruction errors and a topological stability of the underlying
      signal. Our approach offers a valuable method for the evaluation of the
      reconstruction process without the need of visual inspection of the reconstructed
      datasets. By means of qualitative results we show how our proposed topology
      statistics provides complementary information in the enhancement of existing
      reconstruction pipelines in visualization.

PMID- 22865949
TI  - Wavefunction engineering: From quantum wells to near-infrared type-II colloidal
      quantum dots synthesized by layer-by-layer colloidal epitaxy.
AB  - We review the concept and the evolution of bandgap and wavefunction engineering,
      the seminal contributions of Dr. Chemla to the understanding of the rich
      phenomena displayed in epitaxially grown quantum confined systems, and
      demonstrate the application of these concepts to the colloidal synthesis of high
      quality type-II CdTe/CdSe quantum dots using successive ion layer adsorption and
      reaction chemistry. Transmission electron microscopy reveals that CdTe/CdSe can
      be synthesized layer by layer, yielding particles of narrow size distribution.
      Photoluminescence emission and excitation spectra reveal discrete type-II
      transitions, which correspond to energy lower than the type-I bandgap. The
      increase in the spatial separation between photoexcited electrons and holes as a
      function of successive addition of CdSe monolayers was monitored by
      photoluminescence lifetime measurements. Systematic increase in lifetimes
      demonstrates the high level of wavefunction engineering and control in these
      systems.

PMID- 22865950
TI  - The gradual vocal responses to human-provoked discomfort in farmed silver foxes.
AB  - Vocal indicators of welfare have proven their use for many farmed and zoo animals
      and may be applied to farmed silver foxes as these animals display high vocal
      activity toward humans. Farmed silver foxes were selected mainly for fur, size,
      and litter sizes, but not for attitudes to people, so they are fearful of humans
      and have short-term welfare problems in their proximity. With a human approach
      test, we designed here the steady increase and decrease of fox-human distance and
      registered vocal responses of 25 farmed silver foxes. We analyzed the features of
      vocalizations produced by the foxes at different fox-human distances, assuming
      that changes in vocal responses reflect the degrees of human-related discomfort.
      For revealing the discomfort-related vocal traits in farmed silver foxes, we
      proposed and tested the algorithm of "joint calls," equally applicable for
      analysis of all calls independently on their structure, either tonal or noisy. We
      discuss that the increase in proportion of time spent vocalizing and the shift of
      call energy toward higher frequencies may be integral vocal characteristics of
      short-term welfare problems in farmed silver foxes and probably in other captive
      mammals.

PMID- 22865952
TI  - Collaborating With Clients and Improving Outcomes: The Relational Re-enactment
      Systems Approach to Treatment Model.
AB  - The Relational Re-enactment Systems Approach to Treatment model is a coherent and
      comprehensive approach to residential treatment that increases family involvement
      through system-wide clinical consultation. The therapeutic alliance with youth
      and their families is emphasized as the key to creating client-centered goals for
      discharge to a less restrictive environment. The current study examined outcomes
      from four years of the model's implementation. Results indicated a significant
      increase in the proportion of youth discharged to a family home. Additionally,
      the proportion of discharges that were the result of youth running away from
      treatment was reduced by half.

PMID- 22865951
TI  - Atomic layer deposition (ALD): A versatile technique for plasmonics and
      nanobiotechnology.
AB  - While atomic layer deposition (ALD) has been used for many years as an industrial
      manufacturing method for microprocessors and displays, this versatile technique
      is finding increased use in the emerging fields of plasmonics and
      nanobiotechnology. In particular, ALD coatings can modify metallic surfaces to
      tune their optical and plasmonic properties, to protect them against unwanted
      oxidation and contamination, or to create biocompatible surfaces. Furthermore,
      ALD is unique among thin-film deposition techniques in its ability to meet the
      processing demands for engineering nanoplasmonic devices, offering conformal
      deposition of dense and ultra-thin films on high-aspect-ratio nanostructures at
      temperatures below 100  degrees C. In this review, we present key features of ALD
      and describe how it could benefit future applications in plasmonics,
      nanosciences, and biotechnology.

PMID- 22865953
TI  - Pattern Analysis in Neuroimaging: Beyond Two-Class Categorization.
AB  - One of the many advantages of multivariate pattern recognition approaches over
      conventional mass-univariate group analysis using voxel-wise statistical tests is
      their potential to provide highly sensitive and specific markers of diseases on
      an individual basis. However, a vast majority of imaging problems addressed by
      pattern recognition are viewed from the perspective of a two-class
      classification. In this article, we provide a summary of selected works that
      propose solutions to biomedical problems where the widely-accepted classification
      paradigm is not appropriate. These pattern recognition approaches address common
      challenges in many imaging studies: high heterogeneity of populations and
      continuous progression of diseases. We focus on diseases associated with aging
      and propose that clustering-based approaches may be more suitable for
      disentanglement of the underlying heterogeneity, while high-dimensional pattern
      regression methodology is appropriate for prediction of continuous and gradual
      clinical progression from magnetic resonance brain images.

PMID- 22865954
TI  - Age-dependent variation of the Gradient Index profile in human crystalline
      lenses.
AB  - PURPOSE: To reconstruct the gradient index (GRIN) profile of human crystalline
      lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an
      optimization technique and to study the dependence of the GRIN profile with age. 
      METHODS: Cross-sectional images of nine isolated human crystalline lenses with
      ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a
      custom-made OCT system. Lenses were extracted from whole cadaver globes and
      placed in a measurement chamber filled with preservation medium (DMEM). Lenses
      were imaged with the anterior surface up and then flipped over and imaged again,
      to obtain posterior lens surface profiles both undistorted and distorted by the
      refraction through the anterior crystalline lens and GRIN. The GRIN distribution
      of the lens was described with three variables by means of power function, with
      variables being the nucleus and surface index, and a power coefficient that
      describes the decay of the refractive index from the nucleus to the surface. An
      optimization method was used to search for the parameters that produced the best
      match of the distorted posterior surface.  RESULTS: The distorted surface was
      simulated with accuracy around the resolution of the OCT system (under 15 um).
      The reconstructed refractive index values ranged from 1.356 to 1.388 for the
      surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged
      between 3 and 18. The power coefficient increased significantly with age, at a
      rate of 0.24 per year.  CONCLUSION: Optical Coherence Tomography allowed optical,
      non-invasive measurement of the 2-D gradient index profile of the isolated human
      crystalline lens ex vivo. The age-dependent variation of the changes is
      consistent with previous data using magnetic resonance imaging, and the
      progressive formation of a refractive index plateau.

PMID- 22865955
TI  - Morphology-controlled synthesis of silica nanotubes through pH- and sequence
      responsive morphological change of bacterial flagellar biotemplates.
AB  - Bacterial flagella are naturally-occurring self-assembling protein nanofibers
      protruding from the bacterial surface to assist the swimming of bacteria. They
      are rigid and exhibit diverse morphologies depending on the ionic strength, the
      pH values, temperature, and subunit sequences. Here, the silica nanotubes (SNTs)
      with controllable morphologies were synthesized using flagella as biological
      templates in aqueous solution under mild conditions. The morphologies and surface
      features of flagella-templated SNTs can be simply tuned by adjusting the pH value
      or surface chemistry of flagella by peptide display. A variety of different
      morphologies (coiled, straight, and curly with different wavelengths) and surface
      features (smooth, rough, granular and pear-necklace-like) of SNTs were obtained.
      When pH varies from acidic to alkaline conditions, in general, SNTs varied from
      bundled coiled, to characteristic sinusoidal waves, helical, and straight
      morphology. Under genetic control, flagella displaying negatively-charged
      peptides exhibited thinner layer of silica condensation but rough surface.
      However, flagella with positively-charged peptide inserts induced the deposition
      of thicker silica shell with smooth surface. Incorporation of hydroxyl bearing
      amino acid residues such as Ser into the peptide displayed on flagella highly
      enhanced the biotemplated deposition of silica. This work suggests that bacterial
      flagella are promising biotemplates for developing an environmentally-benign and
      cost-efficient approach to morphology-controlled synthesis of nanotubes.
      Moreover, the dependency of the thickness of the silica shell on the peptides
      displayed on flagella helps us to further understand the mechanism of biomimetic
      nucleation of silica on biological templates.

PMID- 22865956
TI  - Microfluidic laminate-based phantom for diffusion tensor-magnetic resonance
      imaging (DT-MRI).
AB  - This paper reports fabrication of a magnetic resonance imaging (MRI) phantom
      created by stacking of multiple thin polydimethylsiloxane (PDMS) layers. PDMS is
      spin coated on SU-8 molds to obtain the desired layer thickness and imprints of
      the microchannel patterns that define the phantom geometry. This paper also
      identifies the unique challenges related to the fabrication and assembly of
      multiple thin layers and reports for the first time assembly of a large number of
      thin laminates of this nature. Use of photolithography techniques allows us to
      create a wide range of phantom geometries. The target dimensions of the phantoms
      reported here are (i) a stack of 30 thin PDMS layers of 10 um thickness (ii)
      curved 5 um * 5 um microchannels with 8.7 um spacing, and (iii) straight 5 um * 5
      um microchannels with 3.6 um spacing. SEM scans of the assembled phantoms show
      open microchannels and a monolithic cross-section with no visible interface
      between PDMS layers. Based on the results of diffusion tensor magnetic resonance
      imaging (DT-MRI) scan, the anisotropic diffusion of water molecules due to the
      physical restriction of the microchannels was detected, which means that the
      phantom can be used to calibrate and optimize MRI instrumentation.

PMID- 22865957
TI  - What to do when there is no standard of care: A brief review of treatment options
      for glioblastoma in children.

PMID- 22865958
TI  - Spontaneous intracerebral hemorrhage: Clinical and computed tomography findings
      in predicting in-hospital mortality in Central Africans.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) constitutes now 52% of all
      strokes. Despite of its deadly pattern, locally there is no clinical grading
      scale for ICH-related mortality prediction. The first objective of this study was
      to develop a risk stratification scale (Kinshasa ICH score) by assessing the
      strength of independent predictors and their association with in-hospital 30-day
      mortality. The second objective of the study was to create a specific local and
      African model for ICH prognosis. MATERIALS AND METHODS: Age, sex, hypertension,
      type 2 diabetes mellitus (T2DM), smoking, alcohol intake, and neuroimaging data
      from CT scan (ICH volume, Midline shift) of patients admitted with primary ICH
      and follow-upped in 33 hospitals of Kinshasa, DR Congo, from 2005 to 2008, were
      analyzed using logistic regression models. RESULTS: A total of 185 adults and
      known hypertensive patients (140 men and 45 women) were examined. 30-day
      mortality rate was 35% (n=65). ICH volume>25 mL (OR=8 95% CI: 3.1-20.2;
      P<0.0001), presence of coma (OR=6.8 95% CI 2.6-17.4; P<0.0001) and left
      hemispheric site of ICH (OR 2.6 95% CI: 1.1-6; P=0.027) were identified as
      significant and independent predictors of 30-day mortality. Midline shift > 7 mm,
      a consequence of ICH volume, was also a significant predictor of mortality. The
      Kinshasa ICH score was the sum of individual points assigned as follows: Presence
      of coma coded 2 (2 * 2 = 4), absence of coma coded 1 (1 * 2 = 2), ICH volume>25
      mL coded 2 (2 * 2=4), ICH volume of <=25 mL coded 1(1 * 2=2), left hemispheric
      site of ICH coded 2 (2 * 1=2), and right hemispheric site of hemorrhage coded 1(1
      * 1 = 1). All patients with Kinshasa ICH score <=7 survived and the patients with
      a score >7 died. In considering sex influence (Model 3), points were allowed as
      follows: Presence of coma (2 * 3 = 6), absence of coma (1 * 3 = 3), men (2 * 2 =
      4), women (1 * 2 = 2), midline shift <=7 mm (1 * 3 = 3), and midline shift >7 mm
      (2 * 3 = 6). Patients who died had the Kinshasa ICH score >=16. CONCLUSION: In
      this study, the Kinshasa ICH score seems to be an accurate method for
      distinguishing those ICH patients who need continuous and special management. It
      needs to be validated among large African hypertensive populations with a high
      rate of 30-day in-hospital mortality.

PMID- 22865959
TI  - Epidural steroid injection in patients with lumbosacral radiculopathy in Abuja,
      Nigeria.
AB  - OBJECTIVE: This prospective-controlled observational study looked at well-matched
      patients with spinal pain and radicular symptoms, caused by lumbar intervertebral
      disc herniation to compare the short-term clinical outcome of transforaminal and
      interlaminar epidural steroid injection (ESI) in a resource challenged tertiary
      institution in Nigeria. MATERIALS AND METHODS: 49 patients with radicular
      symptoms who were matched for age, symptom duration, magnetic resonance imaging
      findings, and pre-injection revised Oswentry Disability Index (ODI) score and
      Visual Analogue Scale (VAS) were assigned into ESI technique. The ODI and VAS
      score were analyzed immediately after an injection and upon follow-up (average
      178.5 days), also with the need for repeated injections and surgical
      interventions over a 1-year follow-up interval. RESULT: In the transforaminal
      group (25 patients), there was a statistically significant improvement in the ODI
      scores from before the injection (ODI mean 62.4) to immediately after the
      injection (ODI mean 24.4, P < 0.01), and upon follow-up (ODI mean 20.8, P <
      0.01). 9 patients (18.4%) required 1 or 2 repeated injections, 3 (6.1%) patients
      underwent surgery and 2 (4%) patients lost to follow-up. In the interlaminar
      group (24 patients), there was a statistically significant improvement in the ODI
      scores from before the injection (ODI mean 60.7) to immediately after the
      injection (ODI mean 30.1, P < 0.01), but not upon follow-up (ODI mean 43.2, P =
      0.09). 11 (22.4%) patients required 1 or 2 repeated injection, 4 (8%) patients
      underwent surgery and 3 (6.1%) patients were lost to follow-up. There is an
      average of 2 fold improvement of transforaminal ESI over interlaminar ESI in a 40
      point scale of ODI score on follow-up, which was statistically significant (P <
      0.01). The VAS showed similar pattern with the ODI scores in the study.
      CONCLUSION: Transforaminal ESI to treat symptomatic lumbar disc herniation
      resulted in better short-term pain improvement and fewer long-term surgical
      interventions compared to interlaminar ESI.

PMID- 22865960
TI  - Lamotrigine effects sensorimotor gating in WAG/Rij rats.
AB  - INTRODUCTION: Prepulse inhibition (PPI) is a measurable form of sensorimotor
      gating. Disruption of PPI reflects the impairment in the neural filtering process
      of mental functions that are related to the transformation of an external stimuli
      to a response. Impairment of PPI is reported in neuropsychiatric illnesses such
      as schizophrenia, Huntington's disease, Parkinson's diseases, Tourette syndrome,
      obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence
      epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is
      an antiepileptic drug that is preferred in absence epilepsy and acts by
      stabilizing the voltage-gated sodium channels. AIM: In this study, we have
      compared WAG-Rij rats (genetically absence epileptic rats) with Wistar rats, in
      order to clarify if there is a deficient sensorimotor gating in absence epilepsy,
      and have examined the effects of lamotrigine (15, 30 mg/kg, i.p.) on this
      phenomenon. MATERIALS AND METHODS: Depletion in PPI percent value is accepted as
      a disruption in sensory-motor filtration function. The difference between the
      Wistar and WAG/Rij rats has been evaluated with the student t test and the
      effects of lamotrigine on the PPI percent have been evaluated by the analysis of
      variance (ANOVA) post-hoc Dunnett's test. RESULTS: The PPI percent was low in the
      WAG/Rij rats compared to the controls (P<0.0001, t:9,612). Although the PPI
      percent value of the control rats was not influenced by lamotrigine, the PPI
      percent value of the WAG/Rij rats was raised by lamotrigine treatment (P<0.0001,
      F:861,24). CONCLUSIONS: As a result of our study, PPI was disrupted in the
      WAG/Rij rats and this disruption could be reversed by an antiepileptic
      lamotrigine.

PMID- 22865961
TI  - Prognostic significance of age in traumatic brain injury.
AB  - BACKGROUND: Age is a strong prognostic factor following traumatic brain injury
      (TBI), with discrepancies defining the critical prognostic age threshold. This
      study was undertaken to determine the impact of various age thresholds on outcome
      after TBI. MATERIALS AND METHODS: The ages of patients admitted with TBI were
      prospectively studied in relation to mode of injury, Glasgow coma score (GCS), CT
      category and surgical intervention. Mortality was assessed at 1 month, and
      neurological outcome was assessed at 6 months. Appropriate statistical analyzes
      (details in article) were performed. RESULTS: Of the total 244 patients enrolled,
      144 patients had severe, 38 patients had moderate and 62 patients had mild TBI,
      respectively. Age had significant association with grade of injury, CT category
      and surgical intervention (P < 0.01). Mortality at 1 month was significantly
      associated with increasing age with patients dead at 1 month being 15% for age <
      18, 44% for age between 18 and 59 years, and 52% in the age group > 59 years
      respectively (P < 0.001). Unfavorable outcome showed significant association with
      an increase in age, every decade (P < 0.001). In multivariate analysis, there was
      stepwise increase in the odds of unfavorable outcome across age groups centered
      on 40 years, independent of confounding factors. The adjusted odds ratios for
      unfavorable outcome with regard to age thresholds 30, 40 and 50 years were 11.3,
      53.3 and 1171, respectively (P < 0.005). Moreover, there was significant
      association of unfavorable outcome with age > 40 years in all subgroups, based on
      GCS and surgical intervention (P < 0.05). CONCLUSIONS: In patients with TBI, age
      demonstrates independent association with unfavorable outcome at 6 months, in
      stepwise manner centered on a threshold of 40 years.

PMID- 22865962
TI  - Commentary.

PMID- 22865963
TI  - Magnetic resonance imaging: Clinical experience with an open low-field-strength
      scanner in a resource challenged African state.
AB  - INTRODUCTION: Despite the fact that an magnetic resonance imaging (MRI) has been
      in clinical use for over 20 years, its use and availability in Nigeria, a West
      African state, is still extremely low. Hence, only few publications are available
      on the clinical experience with MRI from Nigeria. We set out to evaluate our
      initial clinical experience with a low-field-strength MRI in a Nigeria's foremost
      university hospital. MATERIALS AND METHODS: A retrospective review of all
      studies, performed with an open 0.2 Tesla MAGNETOM Concerto (Siemens Medical) MRI
      scanner over a 5-year period (2006 - 2010) was conducted. All patients with
      complete records were evaluated for their clinical and demographic
      characteristics. RESULTS: The records of 799 MRI studies were available.
      Patients' ages ranged from 1 day to 90 years, with a mean of 40.1 years (+/- 20.7
      SD). There were 463 (57.9%) males and 336 (42.1%) females. Over 90% of the
      studies were requested to evaluate brain or spine lesions. Low back pain
      represented the commonest (161/799, 20.7%) clinical indication for MRI. The
      largest number of patients was referred by physicians from surgical specialties
      (65.6%). CONCLUSION: The awareness and competence for proper use of MRI in
      Nigeria appears high. Low back pain is the commonest indication for MRI in our
      institution, and surgeons make a greater use of the facility. The provision of
      high-signal strength MRI may be beneficial in making a wider range of
      applications available to clinicians.

PMID- 22865964
TI  - Effect of fluoride exposure on the intelligence of school children in Madhya
      Pradesh, India.
AB  - OBJECTIVE: To assess the relationship between exposure to different drinking
      water fluoride levels and children's intelligence in Madhya Pradesh state, India.
      MATERIALS AND METHODS: This cross-sectional study was conducted among 12-year-old
      school children of Madhya Pradesh state, India. The children were selected from
      low (< 1.5 parts per million) and high (>=1.5 parts per million) fluoride areas.
      A questionnaire was used to collect information on the children's personal
      characteristics, residential history, medical history, educational level of the
      head of the family, and socioeconomic status of the family. Levels of lead,
      arsenic, and iodine in the urine and the levels of fluoride in the water and
      urine were analyzed. The children's intelligence was measured using Raven's
      Standard Progressive Matrices. Data analysis was done using the chi-square, one
      way analysis of variance, simple linear regression, and multiple linear
      regression tests. P value <0.05 was considered statistically significant.
      RESULTS: Differences in participant's sociodemographic characteristics, urinary
      iodine, urinary lead, and urinary arsenic levels were statistically not
      significant (P>0.05). However, a statistically significant difference was
      observed in the urinary fluoride levels (P 0.000). Reduction in intelligence was
      observed with an increased water fluoride level (P 0.000). The urinary fluoride
      level was a significant predictor for intelligence (P 0.000). CONCLUSION:
      Children in endemic areas of fluorosis are at risk for impaired development of
      intelligence.

PMID- 22865965
TI  - Commentary.

PMID- 22865966
TI  - Commentary.

PMID- 22865967
TI  - Peripheral neurectomies: A treatment option for trigeminal neuralgia in rural
      practice.
AB  - BACKGROUND: Trigeminal neuralgia is a commonly diagnosed neurosensory disease of
      head, neck and face region, involving 5(th) cranial nerve. Carbamazepine is the
      first line drug if there is decrease in efficacy or tolerability of medication,
      surgery needs to be considered. Factors such as pain relief, recurrence rates,
      morbidity and mortality rates should be taken in to account while considering
      which technique to use. Peripheral neurectomy is a safe and effective procedure
      for elderly patients and in rural and remote centers where neurosurgical
      facilities are not available. It is also effective in those patients who are
      reluctant for major neurosurgical procedures. Although loss of sensation along
      the branches of trigeminal nerve and recurrence rate are associated with
      peripheral neurectomy, we consider it as the safe and effective procedure in
      rural practice, which can be done under local anesthesia. AIMS: The aim of this
      prospective study is to evaluate the long term efficacy of peripheral neurectomy
      with and without the placement of stainless steel screws in the foramina and to
      calculate the mean remission period after peripheral neurectomies for different
      branches of trigeminal nerve. SETTING AND DESIGN: The sample was divided into 2
      groups by selecting randomly the patients, satisfying inclusion criteria. Both
      groups were operated under local anesthesia by regional nerve blocks. In one
      group of patients after peripheral neurectomy, the proximal nerve stump was left
      alone in the foramina, and in another group of patients, obturation of foramina
      was done with stainless steel screws after peripheral neurectomy. MATERIALS AND
      METHODS: Peripheral neurectomy was done on the terminal branches of trigeminal
      nerve in 14 patients. We selected only those cases that were experiencing pain
      after Carbamazepine therapy, all our patients were from rural and remote areas
      where facilities to neurosurgical centers are limited. Elderly patients who were
      unfit for surgical procedures and those patients who were reluctant for major
      neurosurgical treatments were considered for the study. RESULTS: Post-surgical
      pain relief varied from 15 months to 24 months in cases where neurectomy was done
      without placing stainless steel screws in the foramina. Those cases where
      peripheral neurectomy was done along with the placement of stainless steel screws
      in the foramina, none of the patient had painful symptoms even after minimum 2
      years of follow-up. Student's 't'-test of 2 groups showed the remission period to
      be statistically highly significant in patients with stainless steel screw
      obturation, having P-value <0.0005.Obturating the foramen with stainless steel
      screws can prevent nerve regeneration. Thus, remission of pain can be prolonged.
      CONCLUSION: Peripheral neurectomy is thus a safe and effective procedure for
      elderly patients, for those patients living in remote and rural places that
      cannot avail major neurosurgical facilities, and for those patients who are
      reluctant for major neurosurgical procedures.

PMID- 22865968
TI  - Commentary.

PMID- 22865969
TI  - Higher sensory processing sensitivity, introversion and ectomorphism: New
      biomarkers for human creativity in developing rural areas.
AB  - The highly sensitive trait present in animals, has also been proposed as a human
      neurobiological trait. People having such trait can process larger amounts of
      sensory information than usual, making it an excellent attribute that allows to
      pick up subtle environmental details and cues. Furthermore, this trait correlates
      to some sort of giftedness such as higher perception, inventiveness, imagination
      and creativity. We present evidences that support the existance of key neural
      connectivity between the mentioned trait, higher sensory processing sensitivity,
      introversion, ectomorphism and creativity. The neurobiological and behavioral
      implications that these biomarkers have in people living in developing rural
      areas are discussed as well.

PMID- 22865971
TI  - Pediatric multifocal glioblastoma multiforme with fulminant course.
AB  - Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor.
      GBM in children is less common than in adults and has a better prognosis.
      Pediatric GBM is a rare entity, and a multifocal development in a pediatric GBM
      is much rarer. We report to you one such rare case of pediatric multifocal GBM in
      a 5-year-old child who developed rapidly increasing multiple lesions after
      radiotherapy. More studies are required to study the genetic analysis, tumor
      behavior, management and outcome of these rare tumors.

PMID- 22865970
TI  - Endoscopic third ventriculostomy.
AB  - Endoscopic third ventriculostomy (ETV) is considered as a treatment of choice for
      obstructive hydrocephalus. It is indicated in hydrocephalus secondary to
      congenital aqueductal stenosis, posterior third ventricle tumor, cerebellar
      infarct, Dandy-Walker malformation, vein of Galen aneurism, syringomyelia with or
      without Chiari malformation type I, intraventricular hematoma, post infective,
      normal pressure hydrocephalus, myelomeningocele, multiloculated hydrocephalus,
      encephalocele, posterior fossa tumor and craniosynostosis. It is also indicated
      in block shunt or slit ventricle syndrome. Proper Pre-operative imaging for
      detailed assessment of the posterior communicating arteries distance from mid
      line, presence or absence of Liliequist membrane or other membranes, located in
      the prepontine cistern is useful. Measurement of lumbar elastance and resistance
      can predict patency of cranial subarachnoid space and complex hydrocephalus,
      which decides an ultimate outcome. Water jet dissection is an effective technique
      of ETV in thick floor. Ultrasonic contact probe can be useful in selected
      patients. Intra-operative ventriculo-stomography could help in confirming the
      adequacy of endoscopic procedure, thereby facilitating the need for shunt.
      Intraoperative observations of the patent aqueduct and prepontine cistern
      scarring are predictors of the risk of ETV failure. Such patients may be
      considered for shunt surgery. Magnetic resonance ventriculography and cine phase
      contrast magnetic resonance imaging are effective in assessing subarachnoid space
      and stoma patency after ETV. Proper case selection, post-operative care including
      monitoring of ICP and need for external ventricular drain, repeated lumbar
      puncture and CSF drainage, Ommaya reservoir in selected patients could help to
      increase success rate and reduce complications. Most of the complications develop
      in an early post-operative, but fatal complications can develop late which
      indicate an importance of long term follow up.

PMID- 22865972
TI  - Transorbital orbitocranial penetrating injury caused by a metal bar.
AB  - Transorbital intracranial injury is uncommon, representing 0.04% of penetrating
      head trauma with a high mortality rate. Orbital penetrating injuries may cause
      severe brain injury if the cranium is entered, typically via the orbital roof,
      the superior orbital fissure, or the optic canal. A 13-year-old male sustained a
      severe brain injury due to penetration of the right orbit with an iron bar. The
      bar entered the inferiomedial aspect of the orbit and emerged from the left
      occipital bone. Neurological examination revealed deep coma (GCS: E1M2V1) with
      fixed, dilated, and non-reactive pupils. The bar followed an intracranial
      trajectory, through the third ventricle and suprasellar cistern. The patient
      underwent an immediate exploration with removal of the bar. Unfortunately, he
      died 10 days postoperatively due to severe diencephalic injury with brainstem
      herniation. In this case report, we discuss the radiologic diagnosis and surgical
      management of transorbital orbitocranial injury by foreign body penetration.

PMID- 22865973
TI  - Cervical disc herniation manifesting as a Brown-Sequard syndrome.
AB  - Brown-Sequard syndrome is commonly seen in the setting of spinal trauma or an
      extramedullary spinal neoplasm. The clinical picture reflects hemisection of the
      spinal cord. We report a rare case of Brown-Sequard syndrome caused by a large
      cervical herniated disc. A 63-year-old man presented with progressive right
      hemiparesis and disruption of pain and temperature sensation on the left side of
      the body. Magnetic resonance imaging showed large C3-C4 disc herniation
      compressing the spinal cord at that level, with severe canal stenosis from C4
      through C7. Decompressive cervical laminoplasty was performed. After surgery,
      complete sensory function was restored and a marked improvement in motor power
      was obtained.

PMID- 22865974
TI  - Commentary.

PMID- 22865975
TI  - Solitary cerebellous metastasis after prolonged remission in a case of uterine
      cervical adenocarcinoma.
AB  - Intracranial metastasis of a uterine cervical carcinoma is a very rare
      occurrence. These metastases are characteristically multiple, supra-tentorial,
      associated with multiple systemic dissemination, usually occur relatively late in
      the course of the disease, and are most often seen in squamous carcinomas. We
      present an unusual case which defied these characteristics. This patient was in
      long-term remission (11 years), presented with a solitary cerebellous metastases,
      had no evidence of other systemic spread, and the pathology was an
      adenocarcinoma. We present this rare case with interesting clinical
      ramifications. This is probably the longest duration of remission prior to the
      metastasis in the published literature.

PMID- 22865976
TI  - Commentary.

PMID- 22865977
TI  - A rare concomitant tubercular and Fonsecaea pedrosoi fungal infection of the
      skull base.
AB  - Tuberculosis of the skull base and middle ear cavity is very rare. Infection with
      neurotropic fungi Fonsecaea pedrosoi is rare, which usually presents as brain
      abscess. We herein present an unusual case of concomitant tuberculosis and fungal
      (Fonsecaea pedrosoi) infections involving the middle ear cleft extending and
      destroying the craniovertebral junction.

PMID- 22865978
TI  - Commentary.

PMID- 22865979
TI  - Idiopathic hypertrophic pachymeningitis presenting with a superficial soft tissue
      mass.
AB  - Idiopathic hypertrophic pachymeningitis (IHP) is a chronic progressive diffuse
      inflammatory fibrosis of the dura-mater, leading to its diffuse enlargement. The
      following describes a case of IHP presenting with a superficial soft tissue mass.
      A 40-year-old female came to hospital with a subcutaneous lump over the left face
      and frontal headache for 6 months. An excision biopsy revealed chronic
      inflammation. Magnetic resonance imaging (MRI) of the brain showed left
      mastoiditis and early dural inflammation of the left temporal region. A few
      months later, she developed diplopia, complex partial seizures, and retrobulbar
      neuritis of the left optic nerve. Repeat MRI brain demonstrated meningeal
      thickening on both sides of the tentorium cerebelli extending to the left tempero
      parietal meninges. The meningeal biopsy revealed markedly thickened fibro
      connective dural tissue with infiltration of chronic inflammatory cells. There
      was no evidence of bacterial, fungal, tuberculous or neoplastic infiltration. IHP
      was diagnosed and steroid therapy initiated. Within weeks, she showed marked
      clinical improvement. IHP is a diagnosis of exclusion. The absence of underlying
      infective, neoplastic, or systemic autoimmune disease favors IHP. The above
      patient had headache, neuro-ophthalmic signs, seizures, which are features of
      IHP. However, superficial soft tissue involvement is rare.

PMID- 22865980
TI  - Commentary.

PMID- 22865981
TI  - Lumbar disk herniation presented with cauda equina syndrome in a pregnant woman.
AB  - Despite low back pain being common in pregnancy, cauda equina syndrome is rare.
      Misdiagnosis and delay in treatment may cause neurological sequelae including
      urinary and fecal incontinence, sexual dysfunction in patients. A case of cauda
      equina syndrome in a pregnant woman at 25-week gestation is presented here. The
      patient underwent an emergency, standard lumbar microdiscectomy under general
      anesthesia on prone position. Neither the patient nor the baby had any
      complication related to surgery.

PMID- 22865982
TI  - Cerebellopontine angle ependymoma in a 2-year- old child.
AB  - The management of cerebellopontine angle (CPA) ependymoma in children below 3
      years of age is challenging. In addition to the rare occurrence of disease, the
      difficulty also lies in achieving gross total resection and providing
      radiotherapy in this subset of patients. We describe a case of CPA ependymoma in
      a 2-year-old child. Gross total excision was achieved followed by administration
      of radiotherapy. In this article, a review of literature for this rare entity and
      the difficulties faced in the surgery and adjuvant treatment has been discussed.

PMID- 22865983
TI  - Cerebrogenic tachyarrhythmia in acute stroke.
AB  - The electrocardiac abnormalities following acute stroke are frequent and seen in
      both ischemic and hemorrhagic stroke. The changes seen in electrocardiogram (ECG)
      consist of repolarization abnormalities such as ST elevation, ST depression,
      negative T waves, and QT prolongation. Among tachyarrhythmias, atrial
      fibrillation is the most common and occurrence of focal atrial tachycardia is
      very rare though any cardiac arrhythmias can follow acute stroke. We report a
      case of focal atrial tachycardia following acute ischemic stroke in 50-year-old
      female without structural heart disease, and their mechanisms and clinical
      implications.

PMID- 22865984
TI  - Carcinomatous meningitis: Yet another cause for rapidly progressive dementia and
      triphasic waves in electroencephalograph!
AB  - We report a 65-year-old woman who manifested with progressive cognitive
      impairment, abnormal behavior, slurred speech, inability to carry out activities
      with right upper limb, gait disturbances, emotional liability, and double
      incontinence that evolved progressively over the last 8 months. A clinical
      syndrome of "rapidly progressive dementia" was considered. The MRI of brain was
      unremarkable except for small para third ventricular enhancing lesion was
      detected in the left thalamic region. There was bi/tri-phasic sharp waves in the
      routine scalp EEG occurring at periodically 1.5-2.0 Hz, mimicking Creutzfeldt
      Jakob disease (CJD). She was later diagnosed to have carcinomatous meningitis
      based on cerebrospinal fluid (CSF) cytology. This case is being discussed for
      rarity and interesting EEG observations in patients with carcinomatous meningitis
      and to highlight the importance of CSF cytology in an appropriate clinical
      setting. One needs to be careful in concluding CJD as possible diagnosis in such
      scenario.

PMID- 22865985
TI  - Commentary.

PMID- 22865986
TI  - Levofloxacin-induced acute anxiety and insomnia.
AB  - Fluoroquinolones can cause adverse neuropsychiatric side effects, which are more
      common in older age. We present three cases of levofloxacin-induced acute anxiety
      and insomnia in young adults. In all the cases, discontinuation of levofloxacin
      immediately lead to remission.

PMID- 22865987
TI  - Commentary.

PMID- 22865988
TI  - Cervical epidural hematoma in a child.
AB  - Pediatric cervical epidural hematoma is an uncommon diagnosis and very few cases
      have been reported so far. The condition is difficult to diagnose and requires
      immediate surgical intervention to obtain the best possible neurological outcome.
      Most of the cases are of a spontaneous origin. We report a case of traumatic
      cervical epidural hematoma, which was managed surgically, resulting in complete
      neurological recovery.

PMID- 22865989
TI  - Gun shot injury as a cause of elevated skull fracture.

PMID- 22865990
TI  - Candida albicans spondylodiscitis in an immunocompetent patient.

PMID- 22865991
TI  - Reversible posterior leukoencephalopathy syndrome.

PMID- 22865992
TI  - Leptospirosis presenting as neuroretinitis.

PMID- 22865993
TI  - Commentary.

PMID- 22865994
TI  - Cerebral fat embolism in a non-head-injured trauma victim: A diagnostic dilemma.

PMID- 22865995
TI  - Dengue encephalitis in children.

PMID- 22865996
TI  - The effect of right or left handedness on caries experience and oral hygiene.

PMID- 22865997
TI  - Aneurysmal bone cyst of the cranio-vertebral junction: Benign or malignant?

PMID- 22865998
TI  - Counterpropagating Rossby waves in confined plane wakes.
AB  - In the present work, we revisit the temporal and the spatio-temporal stability of
      confined plane wakes under the perspective of the counterpropagating Rossby waves
      (CRWs). Within the context of broken line velocity profiles, each vorticity
      discontinuity can be associated to a counterpropagating Rossby wave. In the case
      of a wake modeled by a broken line profile, the interaction of two CRWs is shown
      to originate in a shear instability. Following this description, we first recover
      the stability results obtained by Juniper [J. Fluid Mech. 590, 163-185
      (2007)]10.1017/S0022112007007975 and Biancofiore and Gallaire [Phys. Fluids 23,
      034103 (2011)]10.1063/1.3554764 by means of the classical normal mode analysis.
      In this manner, we propose an explanation of the stabilizing influence of the
      confinement on the temporal stability properties. The CRW description further
      allows us to propose a new interpretation of the counterintuitive spatio-temporal
      destabilization in wake flows at moderate confinement noticed by Juniper [J.
      Fluid Mech. 565, 171-195 (2006)]10.1017/S0022112006001558: it is well predicted
      by the mean group velocity of the uncoupled CRWs.

PMID- 22865999
TI  - The effect of a cognitive-motor intervention on voluntary step execution under
      single and dual task conditions in older adults: a randomized controlled pilot
      study.
AB  - BACKGROUND: This randomized controlled pilot study aimed to explore whether a
      cognitive-motor exercise program that combines traditional physical exercise with
      dance video gaming can improve the voluntary stepping responses of older adults
      under attention demanding dual task conditions. METHODS: Elderly subjects
      received twice weekly cognitive-motor exercise that included progressive strength
      and balance training supplemented by dance video gaming for 12 weeks
      (intervention group). The control group received no specific intervention.
      Voluntary step execution under single and dual task conditions was recorded at
      baseline and post intervention (Week 12). RESULTS: After intervention between
      group comparison revealed significant differences for initiation time of forward
      steps under dual task conditions (U = 9, P = 0.034, r = 0.55) and backward steps
      under dual task conditions (U = 10, P = 0.045, r = 0.52) in favor of the
      intervention group, showing altered stepping levels in the intervention group
      compared to the control group. CONCLUSION: A cognitive-motor intervention based
      on strength and balance exercises with additional dance video gaming is able to
      improve voluntary step execution under both single and dual task conditions in
      older adults.

PMID- 22866000
TI  - Physiological effects beyond the significant gain in muscle mass in sarcopenic
      elderly men: evidence from a randomized clinical trial using a protein-rich food.
AB  - BACKGROUND: Sarcopenia is strongly associated with an inadequate intake of
      dietary protein. Dietary protein supplementation boosts muscle-protein synthesis
      and increases muscle mass in the elderly. This study tested whether adding a
      protein-rich food, ricotta cheese, to the habitual diet increased total
      appendicular skeletal muscle mass and strength in elderly people. METHODS:
      Participants (n = 40), were sarcopenic elderly men and women over 60 years of
      age. Two comparison groups were formed at random and followed for 3 months: the
      intervention group received 210 g/day of ricotta cheese plus the habitual diet,
      while the control group followed the habitual diet with no additional
      intervention. Total appendicular skeletal muscle (TASM) was assessed by dual
      energy X-ray absorptiometry, while strength was measured using a handheld
      dynamometer at baseline and after the intervention period. The primary outcomes
      were the percentage of relative change in TASM and strength. RESULTS: The
      percentage of relative change in TASM was not significant between the groups
      after the intervention period. Muscle strength improved in the intervention
      group, but showed only a tendency towards significance (P = 0.06). Secondary
      analysis showed that the men in the intervention group gained 270 g in TASM
      compared to those in the control group, and improved their fasting insulin levels
      (P = 0.05), muscle strength, lean body mass in the arms, and body weight
      variables. CONCLUSION: The results of this study indicate that a nutritional
      intervention using a high-quality protein food, specifically ricotta cheese, in
      order to increase the amount of protein intake might not be regarded as fully
      promising in elderly men and women with sarcopenia. However, the gender effects
      on muscle strength, lean tissue in the arms, homeostatic assessment of insulin
      resistance, and body weight detected in this study suggest that additional
      research is needed on elderly male subjects with sarcopenia.

PMID- 22866002
TI  - Gabapentin for once-daily treatment of post-herpetic neuralgia: a review.
AB  - Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult
      to the peripheral and central nervous systems caused by the varicella zoster
      virus. Spontaneous pain may result in the persistent sensation of burning,
      tingling, or aching and may be associated with thermally or mechanically provoked
      pain, resulting in hyperalgesia or allodynia. The majority of cases occur in
      patients over the age of 50 years. Gabapentin is a structural analog of gamma
      aminobutyric acid that binds to the alpha(2)-delta site of voltage-dependent
      calcium channels and modulates the influx of calcium, with a resulting reduction
      in excitatory neurotransmitter release. Gabapentin is effective in reducing
      neuropathic pain due to post-herpetic neuralgia when given at least three times
      per day, due to its short half-life, resulting in demonstrable fluctuations in
      plasma levels. Gabapentin has dose-limiting side effects that prevent some
      patients from achieving therapeutic plasma levels, such as somnolence (27.4%),
      dizziness (23.9%), and ataxia (7.1%). GraliseTM is a once-daily extended-release
      formulation of gabapentin that has been developed using AcuFormTM technology.
      AcuForm is a polymer-based drug delivery system that retains the tablet in the
      stomach and upper gastrointestinal tract for a sustained period of time. Once
      daily dosing has been shown to provide comparable drug exposure with an identical
      daily dose of the immediate-release formulation when administered three times
      daily. Participants given Gralise 1800 mg daily had a statistically significant
      reduction in average daily pain intensity scores compared with placebo, reduced
      sleep interference due to pain, and a greater percent of participants reporting
      being much or very much improved on the patient global impression of change. An
      analysis comparing the efficacy and safety profiles in the aging population (>=65
      years) with those younger than 65 years showed that Gralise is effective and well
      tolerated in both age groups.

PMID- 22866001
TI  - Potential role of odanacatib in the treatment of osteoporosis.
AB  - Cathepsin K is a key enzyme involved in the degradation of organic bone matrix by
      osteoclasts. Inhibition of bone resorption observed in human and animal models
      deficient for cathepsin K has identified this enzyme as a suitable target for
      intervention by small molecules with the potential to be used as therapeutic
      agents in the treatment of osteoporosis. Odanacatib (ODN) is a nonbasic selective
      cathepsin K inhibitor with good pharmacokinetic parameters such as minimal in
      vitro metabolism, long half-life, and oral bioavailability. In preclinical
      studies, ovariectomized monkeys and rabbits treated with ODN showed substantial
      inhibition of bone resorption markers along with increases in bone mineral
      density (BMD). Significant differences were observed in the effects of ODN
      treatment compared with those of other antiresorptive agents such as
      bisphosphonates and denosumab. ODN displayed compartment-specific effects on
      trabecular versus cortical bone formation, with treatment resulting in marked
      increases in periosteal bone formation and cortical thickness in ovariectomized
      monkeys whereas trabecular bone formation was reduced. Furthermore, osteoclasts
      remained viable. Phase I and II studies conducted in postmenopausal women showed
      ODN to be safe and well tolerated. After 5 years, women who received ODN 50 mg
      weekly continuously from year 1 (n = 13), showed BMD increases from baseline of
      11.9% at the lumbar spine, 9.8% at the femoral neck, 10.9% at the hip trochanter,
      and 8.5% at the total hip. Additionally, these subjects maintained a low level of
      the urine bone resorption marker N-terminal telopeptide/creatinine (-67.4% from
      baseline) through 5 years of treatment, while levels of serum bone-specific
      alkaline phosphatase remained only slightly reduced relative to baseline (
      15.3%). In women who were switched from ODN to placebo after 2 years, bone
      turnover markers were transiently increased and BMD gains reversed after 12
      months off medication. Adverse experiences in the ODN-treated group were not
      significantly different from the placebo group. In conclusion, available data
      suggests that cathepsin K inhibition could be a promising intervention with which
      to treat osteoporosis. Ongoing studies are expected to provide information on the
      long-term efficacy in fracture reduction and safety of prolonged treatment with
      ODN.

PMID- 22866003
TI  - Nanoinformatics: a new area of research in nanomedicine.
AB  - Over a decade ago, nanotechnologists began research on applications of
      nanomaterials for medicine. This research has revealed a wide range of different
      challenges, as well as many opportunities. Some of these challenges are strongly
      related to informatics issues, dealing, for instance, with the management and
      integration of heterogeneous information, defining nomenclatures, taxonomies and
      classifications for various types of nanomaterials, and research on new modeling
      and simulation techniques for nanoparticles. Nanoinformatics has recently emerged
      in the USA and Europe to address these issues. In this paper, we present a review
      of nanoinformatics, describing its origins, the problems it addresses, areas of
      interest, and examples of current research initiatives and informatics resources.
      We suggest that nanoinformatics could accelerate research and development in
      nanomedicine, as has occurred in the past in other fields. For instance,
      biomedical informatics served as a fundamental catalyst for the Human Genome
      Project, and other genomic and -omics projects, as well as the translational
      efforts that link resulting molecular-level research to clinical problems and
      findings.

PMID- 22866004
TI  - Kaempferol nanoparticles achieve strong and selective inhibition of ovarian
      cancer cell viability.
AB  - Ovarian cancer is one of the leading causes of cancer death for women throughout
      the Western world. Kaempferol, a natural flavonoid, has shown promise in the
      chemoprevention of ovarian cancer. A common concern about using dietary
      supplements for chemoprevention is their bioavailability. Nanoparticles have
      shown promise in increasing the bioavailability of some chemicals. Here we
      developed five different types of nanoparticles incorporating kaempferol and
      tested their efficacy in the inhibition of viability of cancerous and normal
      ovarian cells. We found that positively charged nanoparticle formulations did not
      lead to a significant reduction in cancer cell viability, whereas nonionic
      polymeric nanoparticles resulted in enhanced reduction of cancer cell viability.
      Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol
      led to significant reduction in cell viability of both cancerous and normal
      cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating
      kaempferol resulted in enhanced reduction of cancer cell viability together with
      no significant reduction in cell viability of normal cells compared with
      kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations
      were effective in reducing cancer cell viability, while PLGA nanoparticles
      incorporating kaempferol had selective toxicity against cancer cells and normal
      cells. A PLGA nanoparticle formulation could be advantageous in the prevention
      and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles
      incorporating kaempferol were more effective inhibitors of cancer cells, but they
      also significantly reduced the viability of normal cells. PEO-PPO-PEO
      nanoparticles incorporating kaempferol may be suitable as a cancer-targeting
      strategy, which could limit the effects of the nanoparticles on normal cells
      while retaining their potency against cancer cells. We have identified two
      nanoparticle formulations incorporating kaempferol that may lead to breakthroughs
      in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had
      superior effects compared with kaempferol alone in reducing cancer cell
      viability.

PMID- 22866005
TI  - Actively-targeted LTVSPWY peptide-modified magnetic nanoparticles for tumor
      imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is widely used in modern clinical
      medicine as a diagnostic tool, and provides noninvasive and three-dimensional
      visualization of biological phenomena in living organisms with high spatial and
      temporal resolution. Therefore, considerable attention has been paid to magnetic
      nanoparticles as MRI contrast agents with efficient targeting ability and
      cellular internalization ability, which make it possible to offer higher contrast
      and information-rich images for detection of disease. METHODS: LTVSPWY peptide
      modified PEGylated chitosan (LTVSPWY-PEG-CS) was synthesized by chemical
      reaction, and the chemical structure was confirmed by (1)H-NMR. LTVSPWY-PEG-CS
      modified magnetic nanoparticles were prepared successfully using the solvent
      diffusion method. Their particle size, size distribution, and zeta potential were
      measured by dynamic light scattering and electrophoretic mobility, and their
      surface morphology was investigated by transmission electron microscopy. To
      investigate their selective targeting ability, the cellular uptake of the LTVSPWY
      PEG-CS-modified magnetic nanoparticles was observed in a cocultured system of
      SKOV-3 cells which overexpress HER2 and A549 cells which are HER2-negative. The
      in vitro cytotoxicity of these nanoparticles in SKOV-3 and A549 cells was
      measured using the MTT method. The SKOV-3-bearing nude mouse model was used to
      investigate the tumor targeting ability of the magnetic nanoparticles in vivo.
      RESULTS: The average diameter and zeta potential of the LTVSPWY-PEG-CS-modified
      magnetic nanoparticles was 267.3 +/- 23.4 nm and 30.5 +/- 7.0 mV, respectively,
      with a narrow size distribution and spherical morphology. In vitro cytotoxicity
      tests demonstrated that these magnetic nanoparticles were carriers suitable for
      use in cancer diagnostics with low toxicity. With modification of the LTVSPWY
      homing peptide, magnetic nanoparticles could be selectively taken up by SKOV-3
      cells overexpressing HER2 when cocultured with HER2-negative A549 cells. In vivo
      biodistribution results suggest that treatment with LTVSPWY-PEG-CS-modified
      magnetic nanoparticles/DiR enabled tumors to be identified and diagnosed more
      rapidly and efficiently in vivo. CONCLUSION: LTVSPWY-PEG-CS-modified magnetic
      nanoparticles are a promising contrast agent for early detection of tumors
      overexpressing HER2 and further diagnostic application.

PMID- 22866006
TI  - Endotoxin-induced and vaccine-induced systemic inflammation both impair
      endothelium-dependent vasodilation, but not pulse wave reflection.
AB  - BACKGROUND: Inflammation induced by either endotoxin or vaccination has
      previously been shown to impair endothelium-dependent vasodilation (EDV) in
      healthy young individuals. However, the vascular effects of these two mechanisms
      of inducing inflammation have not been compared in the same individuals. METHODS:
      Twelve young healthy males were studied at the same time of the day on three
      occasions in a random order; on one occasion 4 hours following an endotoxin
      injection (Escherichia coli endotoxin, 20 IU/kg), on another occasion 8 hours
      following vaccination against Salmonella typhi, and on a third occasion 4 hours
      following a saline control injection. EDV and endothelium-independent
      vasodilation (EIDV) were evaluated by local infusions of acetylcholine and sodium
      nitroprusside in the brachial artery, and forearm blood flow was measured with
      venous occlusion plethysmography. The augmentation index was determined by pulse
      wave analysis as an index of pulse wave reflection. RESULTS: Both endotoxin and
      vaccination impaired EDV to a similar degree compared with the saline control (P
      = 0.005 and P = 0.014, respectively). EIDV was not significantly affected by
      inflammation. Endotoxin, but not vaccination, increased body temperature and
      circulating levels of intracellular adhesion molecule-1 and interleukin-6.
      Augmentation index was not affected by the interventions. CONCLUSION: Despite the
      fact that endotoxin induced a more pronounced degree of inflammation than
      vaccination, both inflammatory challenges impaired EDV to a similar degree,
      supporting the view that different inflammatory stimuli could induce harmful
      effects on the vasculature.

PMID- 22866007
TI  - Burden of Crohn's disease: economics and quality of life aspects in Italy.
AB  - BACKGROUND: This was a prospective observational study designed to evaluate
      direct and indirect costs and quality of life for patients with Crohn's disease
      in Italy from the perspectives of the National Health System and of society.
      METHODS: A total of 162 male and female subjects aged 18-70 years with Crohn's
      disease in the active phase and a Crohn's Disease Activity Index score >=150 were
      included in the study. Subjects were recruited from 25 Italian centers on a
      consecutive basis. The study consisted of four visits undertaken every 6 months
      with a follow-up period of 18 months. The study started on September 1, 2006 and
      was completed on April 12, 2010. Multivariate analyses were carried out on
      demographic characteristics, treatment costs based on the prescribed daily dose,
      resource use and other cost parameters, and changes in quality of life using the
      EQ5D questionnaire. RESULTS: Cost of illness per subject with Crohn's disease in
      Italy was estimated to be ?15,521 per year, with direct costs representing 76% of
      total costs. Nonhealth care costs and loss of productivity accounted for 24% of
      total costs. Societal costs during the first months of enrolment were higher
      compared with costs in the final months of the study. Quality of life measured by
      the EQ-5D was 0.558 initially and then increased to 0.739, with a mean value of
      0.677 during the enrolment period. The cost of illness was not correlated with
      age or gender. CONCLUSION: The cost of illness was correlated with quality of
      life; Crohn's disease had a negative impact on subjects' quality of life, and
      higher costs corresponded to a lower quality of life as measured with the EQ5D.
      Drug treatment may improve quality of life and reduce hospitalization costs. Our
      results appear to be in line with the results of other international cost-of
      illness studies.

PMID- 22866008
TI  - Infective endocarditis complicated by aortic graft infection and osteomyelitis:
      case report and review of literature.
AB  - Primary aortic graft infection early after aortic graft insertion is well
      described in the literature. Here, we present a unique case of late aortic graft
      infection 5 years after insertion secondary to mitral valve endocarditis,
      resulting from cellulitis in a patient with severe venous varicosities. A 63-year
      old male presented for severe low back pain, constipation, and low-grade fever.
      An abdominal computed tomography scan with oral and intravenous contrast showed a
      normal spine and urinary tract. Blood and urine cultures, done at the same time,
      grew Staphylococcus aureus. A transesophageal echocardiogram confirmed the
      diagnosis of endocarditis. Subsequently, a gallium scan showed increased uptake
      in the vertebral bodies, aortic graft, left patella, and left ankle. After 3
      months of antibiotic therapy, the patient's low back pain resolved with
      normalization of his laboratory values. He remained free of infection at a 2-year
      follow-up. We reviewed the literature concerning the atypical presentation of
      infective endocarditis, with a focus on distant metastases at initial
      presentation, such as osteomyelitis and aortic graft infection, as well as the
      different treatment modalities. This report describes successful medical
      treatment with intravenous followed by oral antibiotics for an infected
      endovascular graft without any surgical intervention.

PMID- 22866009
TI  - Effects of diet-induced obesity on protein expression in insulin signaling
      pathways of skeletal muscle in male Wistar rats.
AB  - BACKGROUND: The prevalence of diet-induced obesity is increasing globally, and
      posing significant health problems for millions of people worldwide. Diet-induced
      obesity is a major contributor to the global pandemic of type 2 diabetes
      mellitus. The reduced ability of muscle tissue to regulate glucose homeostasis
      plays a major role in the development and prognosis of type 2 diabetes. In this
      study, an animal model of diet-induced obesity was used to elucidate changes in
      skeletal muscle insulin signaling in obesity-induced diabetes. METHODS: Adult
      male Wistar rats were randomized and assigned to either a control group or to a
      test group. Controls were fed a standard laboratory pellet diet (chow-fed), while
      the test group had free access to a highly palatable diet (diet-fed). After 8
      weeks, the diet-fed animals were subdivided into three subgroups and their diets
      were altered as follows: diet-to-chow, diet-fed with addition of fenofibrate
      given by oral gavage for a further 7 weeks, or diet-fed with vehicle given by
      oral gavage for a further 7 weeks, respectively. RESULTS: Untreated diet-fed
      animals had a significantly higher body weight and metabolic profile than the
      control chow-fed animals. Intramuscular triacylglyceride levels in the untreated
      obese animals were significantly higher than those in the control chow-fed group.
      Expression of protein kinase C beta, phosphatidylinositol 3, Shc, insulin
      receptor substrate 1, ERK1/2, and endothelial nitric oxide synthase was
      significantly increased by dietary obesity, while that of insulin receptor beta,
      insulin receptor substrate 1, and protein kinase B (Akt) were not affected by
      obesity. CONCLUSION: These data suggest that diet-induced obesity affects insulin
      signaling mechanisms, leading to insulin resistance in muscle.

PMID- 22866010
TI  - Blood urea nitrogen to serum albumin ratio independently predicts mortality and
      severity of community-acquired pneumonia.
AB  - BACKGROUND: Early studies of community-acquired pneumonia showed that
      nonsurvivors had higher blood urea nitrogen levels and lower serum albumin levels
      than survivors. Therefore, elevation of the blood urea nitrogen to serum albumin
      (B/A) ratio may identify patients with community-acquired pneumonia who are
      becoming critically ill. This study investigated the correlation between commonly
      used laboratory markers, in particular the B/A ratio, and clinical outcomes of
      community-acquired pneumonia. METHODS: This observational study was performed in
      consecutive patients with community-acquired pneumonia admitted to our hospital
      over a period of one year. Blood counts, commonly used laboratory markers,
      microbiological tests, and calculation of Pneumonia Severity Index (PSI) and CURB
      65 were done on admission. The endpoints were mortality within 28 days of
      admission and requirement for intensive care. RESULTS: One hundred and seventy
      five patients with community-acquired pneumonia were enrolled. Nineteen patients
      died within 28 days of admission and 29 patients required intensive care. Using
      multivariate analysis, independent factors associated with mortality were the
      requirement for intensive care (odds ratio [OR] 14.96, 95% confidence interval
      [CI] 3.73-60.03, P < 0.001), PSI class (OR 3.55, 95% CI 1.08-11.66, P = 0.037),
      and B/A ratio (OR 1.10, 95% CI 1.01-1.20, P = 0.037). Similarly, independent
      factors associated with need for intensive care were PSI class (OR 5.35, 95% CI
      1.90-15.06, P = 0.002), CURB-65 (OR 2.37, 95% CI 1.26-4.45, P = 0.007), and B/A
      ratio (OR 1.27, 95% CI 1.09-1.47, P = 0.002). CONCLUSION: The B/A ratio is a
      simple but independent predictor of mortality and severity of community-acquired
      pneumonia.

PMID- 22866011
TI  - Irrational parenthood cognitions and health-related quality of life among
      infertile women.
AB  - BACKGROUND: The aim of this study was to assess health-related quality of life,
      irrational parenthood cognitions, and their interrelationship among a group of
      Iranian women referred to an infertility center in Tehran, the capital of Iran.
      MATERIALS AND METHODS: Women who visited the infertility center in Imam Khomeini
      University Hospital in Tehran participated in this cross-sectional study. Each
      participant filled out a two-part questionnaire. The first part included
      background questions, and the second part included inventories developed to
      assess quality of life and irrational parenthood cognition among infertile
      subjects. RESULTS: The mean age of the participants was 27.8 years (standard
      deviation, 5.1). Mean standardized quality of life score was 59.4 out of a
      maximum of 100 (95% confidence interval, 56-62.8). No statistically significant
      linear correlation was found between quality of life and age, length of marriage,
      or the time under treatment. There was a weak reverse correlation between length
      of the time attempting to become pregnant and quality of life (r = -0.25; P <
      0.01). There was a strong reverse correlation between irrational parenthood
      cognitions and quality of life (r = -0.64; P < 0.00). Multivariate regression
      analysis found several variables to be independent predictors of quality of life
      score. These included having higher levels of irrational parenthood cognitions,
      being under high social pressure imposed by relatives, and having spent a long
      time attempting to become pregnant. CONCLUSION: Knowing about the predictors of
      low quality of life (including high-level irrational parenthood cognitions,
      social pressure from relatives, and spending a long time attempting to become
      pregnant) is assumed to help physicians in identifying the infertile women who
      are at higher risk of developing a poor health over their infertility experience.

PMID- 22866012
TI  - Main causes of death among Swedish women born 1914 and 1918: 32-year follow-up of
      the Population Study of Women in Gothenburg.
AB  - BACKGROUND: Coronary heart disease has been reported to be the major cause of
      death of postmenopausal women in industrialized countries. The risk for women of
      dying from myocardial infarction is significantly greater than the risk of dying
      from cancer. The aim of this study was to compare previous observations regarding
      causes of death with the results from the Population Study of Women in
      Gothenburg. We also examined how causes of deaths vary among different age
      cohorts. METHODS: This follow-up report based on the prospective observational
      Population Study of Women in Gothenburg, Sweden was confined to mortality in two
      age cohorts: 180 women born in 1914 and 398 women born in 1918. These women were
      representative of the female population in Gothenburg in these age groups. Women
      were followed for 32 years, from 1968-1969 to 2000-2001. During the follow-up
      period, data on mortality were obtained from the population registry and the
      Cause of Death Register. Women's death certificates were also examined. RESULTS:
      In women aged between 60 and 80 years, cancer accounted for 30% of deaths,
      myocardial infarction for 19%, and stroke for 14%. In women who died after the
      age of 80 years, myocardial infarction was a more common cause of death than
      cancer. CONCLUSIONS: Cancer accounts for most years lost from a woman's normal
      life span. Myocardial infarction was a more common cause of death than cancer
      only in women above the age of 80 years. Although myocardial infarction is a
      common cause of death among women, cancer is a more common cause of death at
      younger ages. This should be emphasized when planning care, prevention, and
      research involving women's health.

PMID- 22866013
TI  - Application of Haddon's matrix in qualitative research methodology: an experience
      in burns epidemiology.
AB  - BACKGROUND: Little has been done to investigate the application of injury
      specific qualitative research methods in the field of burn injuries. The aim of
      this study was to use an analytical tool (Haddon's matrix) through qualitative
      research methods to better understand people's perceptions about burn injuries.
      METHODS: This study applied Haddon's matrix as a framework and an analytical tool
      for a qualitative research methodology in burn research. Both child and adult
      burn injury victims were enrolled into a qualitative study conducted using focus
      group discussion. Haddon's matrix was used to develop an interview guide and also
      through the analysis phase. RESULTS: The main analysis clusters were pre-event
      level/human (including risky behaviors, belief and cultural factors, and
      knowledge and education), pre-event level/object, pre-event phase/environment and
      event and post-event phase (including fire control, emergency scald and burn
      wound management, traditional remedies, medical consultation, and severity
      indicators). This research gave rise to results that are possibly useful both for
      future injury research and for designing burn injury prevention plans.
      CONCLUSION: Haddon's matrix is applicable in a qualitative research methodology
      both at data collection and data analysis phases. The study using Haddon's matrix
      through a qualitative research methodology yielded substantially rich information
      regarding burn injuries that may possibly be useful for prevention or future
      quantitative research.

PMID- 22866014
TI  - Multiple multilayer stents for thoracoabdominal aortic aneurysm: a possible new
      tool for aortic endovascular surgery.
AB  - PURPOSE: Endovascular surgery data are confirming the paramount role of modern
      endovascular tools for a safe and sure exclusion of thoracoabdominal lesions.
      CASE REPORT: A 57-year-old female presented with severe comorbidity affected by a
      58 mm thoracoabdominal aortic aneurysm (TAAA). After patient-informed consent and
      local Ethical Committee and Italian Public Health Ministry authorization, three
      multilayer stents were implanted in the thoracoabdominal aortic tract, obtaining
      at a 20-month computed tomography scan follow up, a complete exclusion of the
      TAAA, with normal patency of visceral vessels. CONCLUSION: Multilayer stents can
      be used in thoracoabdominal aortic aneurysm, with positive results.

PMID- 22866015
TI  - Quality of life in patients with skin diseases in central Saudi Arabia.
AB  - BACKGROUND: Previous national and international studies of quality of life (QoL)
      in patients with skin diseases have revealed different levels of QoL impairment.
      The aims of this study were to assess QoL in patients with skin diseases in
      central Saudi Arabia using the newly validated Skindex-16 instrument and to
      determine the association between QoL in patients with skin disease,
      sociodemographic data, and disease characteristics. METHODS: A cross-sectional
      study was conducted in 283 adult patients who visited the outpatient dermatology
      clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia, over 3 months. The
      patients were interviewed using a pretested Arabic version of the Skindex-16 to
      measure the effect of skin disorders on their QoL during the previous 7 days.
      Patient characteristics, medical history, and clinical findings were collected.
      Multiple linear regression analyses were used to relate the demographic and
      clinical characteristics to the percentage mean QoL score, and P <= 0.05 was
      considered to be statistically significant. RESULTS: QoL was good in 69% of the
      respondents, with a total percent mean score of 31.80 +/- 20.16. The emotional
      domain was the most affected (mean percentage score 44.27 +/- 27.06), followed by
      symptoms (31.45 +/- 28.40) and functioning (14.61 +/- 22.75). After adjustment
      for potential confounders, poorer QoL was significantly associated with female
      gender (P = 0.03), older age (P = 0.003), rural origin (P = 0.03), positive
      family history of the same lesion(s) (P = 0.01), shorter duration of <=6 months
      (P = 0.02), generalized spread (P <= 0.02), and lack of isotretinoin treatment (P
      = 0.02). CONCLUSION: . The QoL results in this study were generally more
      optimistic than those of many previous studies. This discrepancy may be due to
      biases in questionnaire responses or to cultural differences in experience of
      skin disease and perception of disability. Significant predictors of QoL were not
      the same for the three domains of the Skindex scale. Further studies of specific
      diseases and educational programs targeting patients at higher risk for QoL
      impairments are recommended.

PMID- 22866017
TI  - Acute respiratory distress syndrome: epidemiology and management approaches.
AB  - Acute lung injury and the more severe acute respiratory distress syndrome
      represent a spectrum of lung disease characterized by the sudden onset of
      inflammatory pulmonary edema secondary to myriad local or systemic insults. The
      present article provides a review of current evidence in the epidemiology and
      treatment of acute lung injury and acute respiratory distress syndrome, with a
      focus on significant knowledge gaps that may be addressed through epidemiologic
      methods.

PMID- 22866018
TI  - Validity and reproducibility of a physical activity questionnaire for older
      adults: questionnaire versus accelerometer for assessing physical activity in
      older adults.
AB  - BACKGROUND: Physical activity (PA) is important in older adults for the
      maintenance of functional ability. Assessing PA may be difficult. Few PA
      questionnaires have been compared to activity monitors. We examined
      reproducibility and validity of the self-administered Longitudinal Ageing Study
      Amsterdam Physical Activity Questionnaire (LAPAQ) against a triaxial
      accelerometer (ACTR) (Sensewear((r)) Pro) in older adults. METHODS: Participants
      wore the ACTR continuously for two weeks. After 2 (T [time] = 1) and 4 (T = 2)
      weeks, participants completed the LAPAQ. Since the LAPAQ asks about 2 weeks'
      worth of physical activity, the ACTR and LAPAQ coincided at T1. T2 was used to
      assess the reproducibility of the LAPAQ results only. We calculated Pearson's
      correlation coefficients (PCC) to examine reproducibility and validity. For
      visualization, we used scatterplots and Bland-Altman plots. With a receiver
      operating characteristics (ROC) curve we assessed how well the LAPAQ identifies
      older adults whose activity level is below official recommendations. RESULTS: A
      total of 89 persons were included. Of the participants, 48% were men; median age
      was 73, and median body mass index was 25. The 2-week mean total duration of
      activity was 2788 (ACTR, T = 1), 2439 (LAPAQ T = 1), and 1994 (LAPAQ T = 2)
      minutes. As a reference, 2 full weeks contained 20,160 minutes. Reproducibility
      of the LAPAQ was moderate (PCC 0.68, 95% CI 0.55-0.80). The median difference
      between LAPAQ at T = 1 and the ACTR (LAPAQ minus ACTR) was -510 minutes and the
      PCC was 0.25 (95% CI 0.07-0.44). The area under the ROC curve was 0.73 (95% CI
      0.59-0.86). CONCLUSION: LAPAQ underestimates PA and seems unsuitable for exact
      measurement in older adults. However, it may be used to determine if a person's
      PA level is below the recommended level.

PMID- 22866019
TI  - Quality of life and baseline characteristics associated with depressive symptoms
      among patients with heart disease.
AB  - We sought to examine factors associated with depressive symptoms among patients
      with heart disease. Data from 197 patients admitted for coronary artery disease
      were examined using multivariate predictive models. Women and unmarried patients
      were more likely to report depressive symptoms. In multivariate models, we
      observed that depressive symptoms were associated with the level of tangible
      social (but not emotional) support, bodily pain, and vitality, but not the number
      of comorbidities, gender, or marital status.

PMID- 22866020
TI  - Developmental outcomes of Down syndrome and Dandy-Walker malformation.
AB  - Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain
      malformation of the posterior fossa, typically resulting in developmental delay
      and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is
      relatively uncommon; thus, its impact on developmental outcomes has not been
      fully elucidated. Herein, we report a case of a 37-month-old child with DS and
      DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo
      level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As
      such, it is important to determine how the DWS influences developmental outcomes,
      and appreciate the importance of early interventional therapy.

PMID- 22866021
TI  - Identification of Phosphorylated Human Peptides by Accurate Mass Measurement
      Alone.
AB  - At sufficiently high mass accuracy, it is possible to distinguish phosphorylated
      from unmodified peptides by mass measurement alone. We examine the feasibility of
      that idea, tested against a library of all possible in silico tryptic digest
      peptides from the human proteome database. The overlaps between in silico tryptic
      digest phosphopeptides generated from known phosphorylated proteins (1-12 sites)
      and all possible unmodified human peptides are considered for assumed mass error
      ranges of +/-10, +/-50, +/-100, +/-1,000, and +/-10,000 ppb. We find that for
      mass error +/-50 ppb, 95% of all phosphorylated human tryptic peptides can be
      distinguished from nonmodified peptides by accurate mass alone through the entire
      nominal mass range. We discuss the prospect of on-line LC MS/MS to identify
      phosphopeptide precursor ions in MS1 for selected dissociation in MS2 to identify
      the peptide and site(s) of phosphorylation.

PMID- 22866022
TI  - Inhibition of impurities formation in the synthesis of N-alkyltheobromines
      stimulated by microwave irradiation. Cationic and anionic response of membrane
      electrodes.
AB  - N-Alkyltheobromine (1-9) derivatives were obtained by reacting theobromine with
      appropriate alkyl halide under microwave irradiation at 100-150 W and by
      conventional synthesis. Formation of by-products of oxygen atom alkylation and 1
      N-alkyltheobromine ring opening were considered. The presented compounds 1-5 have
      been studied as ion carriers in ion-selective membrane electrodes. Selectivity of
      these membranes was studied towards various anions in addition to transition and
      heavy metal cations.  GRAPHICAL ABSTRACT: Alkylations of theobromine under
      microwave irradiation at 100-150 W and by conventional synthesis were performed.
      Formation of by-products of oxygen atom alkylation and 1-N-alkyltheobromine ring
      opening were observed. The achieved compounds have been studied as ion carriers
      in ion-selective membrane electrodes.

PMID- 22866023
TI  - Building Health Literacy Among an Urban Teenage Population by Creating Online
      Health Videos for Public and School Health Curriculum Use.
AB  - Healthflicks is a 2010-2011 National Network of Libraries of Medicine outreach
      project conducted in New Haven, CT, targeting health information literacy among
      urban teens through the creation of web videos. Students from a public magnet
      school with a health careers curriculum track volunteered. Yale University
      students were hired as video mentors. Partners included the Cushing/Whitney
      Medical Library, Hill Regional Career High School, the New Haven Free Public
      Library, and Yale University's Office of New Haven and State Affairs. Outcomes
      included a Healthflicks YouTube channel and an ongoing partnership between an
      academic medical library and a high school with a health careers curriculum
      track.

PMID- 22866024
TI  - Information Seeking about Global Climate Change among Adolescents: The Role of
      Risk Perceptions, Efficacy Beliefs and Parental Influences.
AB  - Global climate change is likely to have significant impacts on public health.
      Effective communication is critical to informing public decision making and
      behavior to mitigate climate change. An effective method of audience
      segmentation, the risk perception attitude (RPA) framework has been previously
      tested with other health behaviors and classifies people into 4 groups on the
      basis of their perceptions of risk and beliefs about personal efficacy. The 4
      groups - indifference (low risk, weak efficacy), proactive (low risk, strong
      efficacy), avoidance (high risk, weak efficacy), and responsive (high risk,
      strong efficacy) - are hypothesized to differ in their self-protective behaviors
      and in their motivations to seek information. In this paper, we extend the RPA
      framework in two ways. First, we use it at the household level to determine
      whether parental classifications into the 4 groups are associated with their
      teenage children's classification into the same 4 groups. Second, we predict
      adolescent information-seeking behaviors on the basis of their and their parents'
      membership in the 4 RPA groups. Results (N = 523 parent-adolescent pairs)
      indicated that parental membership in the 4 RPA groups was significantly
      associated with children's membership in the same 4 groups. Furthermore, the RPA
      framework was a significant predictor of adolescent information-seeking: those in
      the responsive and avoidance groups sought more information on climate change
      than the indifference group. Family communication on global warming was
      positively associated with adolescents' information-seeking. Implications for
      interventions are discussed.

PMID- 22866025
TI  - Clinical Assessment of Central Blood Pressure.
AB  - Central aortic blood pressure (CBP) is increasingly considered a better
      cardiovascular prognostic marker than conventional cuff brachial blood pressure.
      Because CBP cannot be directly measured noninvasively, it has to be estimated
      from peripheral pressure pulses. To assess estimated CBP appropriately, the
      accuracy and features of the estimation method should be considered. The aim of
      this review is to provide basic knowledge and information useful for interpreting
      and assessing estimated CBP from a methodological point of view. Precise
      peripheral pressure pulse recording has been enabled by the introduction of
      arterial applanation tonometry, for which the radial artery may be the optimal
      site. An automated tonometry device utilizing a sensor array is preferable in
      terms of reproducibility and objectivity. Calibration of a peripheral pressure
      waveform has unresolved problems for any estimation method, due to imperfect
      brachial sphygmomanometry. However, if central and peripheral pressure
      calibrations are equivalent, two major methods to estimate CBP-those based on
      generalized pressure transfer function or radial late systolic pressure-may be
      comparable in their accuracy of CBP parameter estimation.

PMID- 22866026
TI  - A Review of Shearwave Dispersion Ultrasound Vibrometry (SDUV) and its
      Applications.
AB  - Measurement of tissue elasticity has emerged as an important advance in medical
      imaging and tissue characterization. However, soft tissue is inherently a
      viscoelastic material. One way to characterize the viscoelastic material
      properties of a material is to measure shear wave propagation velocities within
      the material at different frequencies and use the dispersion of the velocities,
      or variation with frequency, to solve for the material properties. Shearwave
      Dispersion Ultrasound Vibrometry (SDUV) is an ultrasound-based technique that
      uses this feature to characterize the viscoelastic nature of soft tissue. This
      method has been used to measure the shear elasticity and viscosity in various
      types of soft tissues including skeletal muscle, cardiac muscle, liver, kidney,
      prostate, and arterial vessels. This versatile technique provides measurements of
      viscoelastic material properties with high spatial and temporal resolution, which
      can be used for assessing these properties in normal and pathologic tissues. The
      goals of this paper are to 1) give an overview of viscoelasticity and shear wave
      velocity dispersion, 2) provide a history of the development of the SDUV method,
      and 3) survey applications for SDUV that have been previously reported.

PMID- 22866027
TI  - Influence of point mutations on the stability, dimerization, and oligomerization
      of human cystatin C and its L68Q variant.
AB  - Human cystatin C (hCC) is a small but very intriguing protein. Produced by all
      nucleated cells is found in almost all tissues and body fluids where, at
      physiological conditions, plays a role of a very potent inhibitor of cysteine
      proteases. Biologically active hCC is a monomeric protein but during cellular
      trafficking it forms dimers, transiently losing its inhibitory activity. In
      vitro, dimerization of cystatin C was observed for the mature protein during
      crystallization trials, revealing that the mechanism of this process is based on
      the three dimensional swapping of the protein domains. In our work we have
      focused on the impact of two proposed "hot spots" in cystatin C structure on its
      conformational stability. Encouraged by promising results of the theoretical
      calculations, we designed and produced several hCC hinge region point mutation
      variants that display a variety of conformational stability and propensity for
      dimerization and aggregation. A similar approach, i.e., rational mutagenesis, has
      been also applied to study the amyloidogenic L68Q variant to determine the
      contribution of hydrophobic interactions and steric effect on the stability of
      monomeric cystatin C. In this overview we would like to summarize the results of
      our studies. The impact of a particular mutation on the properties of the studied
      proteins will be presented in the context of their thermal and mechanical
      stability, in vitro dimerization tendency as well as the outcome of
      crystallization. Better understanding of the mechanism and, especially, factors
      affecting conformational stability of cystatin C and access to stable monomeric
      and dimeric versions of the protein opens new perspectives in explaining the role
      of dimers and the domain swapping process in hCC oligomerization, as well as
      designing potential inhibitors of this process.

PMID- 22866029
TI  - Novel recombinant adeno-associated viruses for Cre activated and inactivated
      transgene expression in neurons.
AB  - Understanding the organization of the nervous system requires methods for
      dissecting the contributions of each component cell type to circuit function. One
      widely used approach combines genetic targeting of Cre recombinase to specific
      cell populations with infection of recombinant adeno-associated viruses (rAAVs)
      whose transgene expression is activated by Cre ("Cre-On"). Distinguishing how the
      Cre-expressing neurons differ functionally from neighboring Cre-negative neurons
      requires rAAVs that are inactivated by Cre ("Cre-Off") and can be used in tandem
      with Cre-On viruses. Here we introduce two rAAV vectors that are inactivated by
      Cre and carry different fluorophore and optogenetic constructs. We demonstrate
      single and dual rAAV systems to achieve Cre-On and Cre-Off expression in
      spatially-intermingled cell populations of the striatum. Using these systems, we
      uncovered cryptic genomic interactions that occur between multiple Cre-sensitive
      rAAVs or between Cre-sensitive rAAVs and somatic Cre-conditional alleles and
      devised methods to avoid these interactions. Our data highlight both important
      experimental caveats associated with Cre-dependent rAAV use as well as
      opportunities for the development of improved rAAVs for gene delivery.

PMID- 22866028
TI  - Dopaminergic axon guidance: which makes what?
AB  - Mesotelencephalic pathways in the adult central nervous system have been studied
      in great detail because of their implication in major physiological functions as
      well as in psychiatric, neurological, and neurodegenerative diseases. However,
      the ontogeny of these pathways and the molecular mechanisms that guide
      dopaminergic axons during embryogenesis have been only recently studied. This
      line of research is of crucial interest for the repair of lesioned circuits in
      adulthood following neurodegenerative diseases or common traumatic injuries. For
      instance, in the adult, the anatomic and functional repair of the nigrostriatal
      pathway following dopaminergic embryonic neuron transplantation suggests that
      specific guidance cues exist which govern embryonic fibers outgrowth, and
      suggests that axons from transplanted embryonic cells are able to respond to
      theses cues, which then guide them to their final targets. In this review, we
      first synthesize the work that has been performed in the last few years on
      developing mesotelencephalic pathways, and summarize the current knowledge on the
      identity of cellular and molecular signals thought to be involved in establishing
      mesotelencephalic dopaminergic neuronal connectivity during embryogenesis in the
      central nervous system of rodents. Then, we review the modulation of expression
      of these molecular signals in the lesioned adult brain and discuss their
      potential role in remodeling the mesotelencephalic dopaminergic circuitry, with a
      particular focus on Parkinson's disease (PD). Identifying guidance molecules
      involved in the connection of grafted cells may be useful for cellular therapy in
      Parkinsonian patients, as these molecules may help direct axons from grafted
      cells along the long distance they have to travel from the substantia nigra to
      the striatum.

PMID- 22866030
TI  - An amplified promoter system for targeted expression of calcium indicator
      proteins in the cerebellar cortex.
AB  - Recording of identified neuronal network activity using genetically encoded
      calcium indicators (GECIs) requires labeling that is cell type-specific and
      bright enough for the detection of functional signals. However, specificity and
      strong expression are often not achievable using the same promoter. Here we
      present a combinatorial approach for targeted expression and single-cell-level
      quantification in which a weak promoter is used to drive trans-amplification
      under a strong general promoter. We demonstrated this approach using recombinant
      adeno-associated viruses (rAAVs) to deliver the sequence of the GECI D3cpv in the
      mouse cerebellar cortex. Direct expression under the human synapsin promoter
      (hSYN) led to high levels of expression (50-100 MUM) in five interneuron types of
      the cerebellar cortex but not in Purkinje cells (PCs) (<=10 MUM), yielding
      sufficient contrast to allow functional signals to be recorded from somata and
      processes in awake animals using two-photon microscopy. When the hSYN promoter
      was used to drive expression of the tetracycline transactivator (tTA), a second
      rAAV containing the bidirectional TET promoter (P(tet)bi) could drive strong
      D3cpv expression in PCs (10-300 MUM), enough to allow reliable complex spike
      detection in the dendritic arbor. An amplified approach should be of use in
      monitoring neural processing in selected cell types and boosting expression of
      optogenetic probes. Additionally, we overcome cell toxicity associated with rAAV
      injection and/or local GECI overexpression by combining the virus injection with
      systemic pre-injection of hyperosmotic D-mannitol, and by this double the time
      window for functional imaging.

PMID- 22866031
TI  - Beyond traditional approaches to understanding the functional role of
      neuromodulators in sensory cortices.
AB  - Over the last two decades, a vast literature has described the influence of
      neuromodulatory systems on the responses of sensory cortex neurons (review in Gu,
      2002; Edeline, 2003; Weinberger, 2003; Metherate, 2004, 2011). At the single cell
      level, facilitation of evoked responses, increases in signal-to-noise ratio, and
      improved functional properties of sensory cortex neurons have been reported in
      the visual, auditory, and somatosensory modality. At the map level, massive
      cortical reorganizations have been described when repeated activation of a
      neuromodulatory system are associated with a particular sensory stimulus. In
      reviewing our knowledge concerning the way the noradrenergic and cholinergic
      system control sensory cortices, I will point out that the differences between
      the protocols used to reveal these effects most likely reflect different
      assumptions concerning the role of the neuromodulators. More importantly, a gap
      still exists between the descriptions of neuromodulatory effects and the concepts
      that are currently applied to decipher the neural code operating in sensory
      cortices. Key examples that bring this gap into focus are the concept of cell
      assemblies and the role played by the spike timing precision (i.e., by the
      temporal organization of spike trains at the millisecond time-scale) which are
      now recognized as essential in sensory physiology but are rarely considered in
      experiments describing the role of neuromodulators in sensory cortices. Thus, I
      will suggest that several lines of research, particularly in the field of
      computational neurosciences, should help us to go beyond traditional approaches
      and, ultimately, to understand how neuromodulators impact on the cortical
      mechanisms underlying our perceptual abilities.

PMID- 22866033
TI  - Binocular rivalry produced by temporal frequency differences.
AB  - When the eyes view images that are sufficiently different to prevent binocular
      fusion, binocular rivalry occurs and the images are seen sequentially in a
      stochastic alternation. Here we examine whether temporal frequency differences
      will trigger binocular rivalry by presenting two dynamic random-pixel arrays that
      are spatially matched but which modulate temporally at two different rates. We
      found that binocular rivalry between the two temporal frequencies did indeed
      occur, provided the frequencies were sufficiently different. Differences greater
      than two octaves (i.e., a factor of four) produced robust rivalry with clear-cut
      alternations similar to those experienced with spatial rivalry and with similar
      alternation rates. This finding indicates that temporal information can produce
      binocular rivalry in the absence of spatial conflict and is discussed in terms of
      rivalry requiring conflict between temporal channels.

PMID- 22866032
TI  - What can other animals tell us about human social cognition? An evolutionary
      perspective on reflective and reflexive processing.
AB  - Human neuroscience has seen a recent boom in studies on reflective, controlled,
      explicit social cognitive functions like imitation, perspective-taking, and
      empathy. The relationship of these higher-level functions to lower-level,
      reflexive, automatic, implicit functions is an area of current research. As the
      field continues to address this relationship, we suggest that an evolutionary,
      comparative approach will be useful, even essential. There is a large body of
      research on reflexive, automatic, implicit processes in animals. A growing
      perspective sees social cognitive processes as phylogenically continuous, making
      findings in other species relevant for understanding our own. One of these
      phylogenically continuous processes appears to be self-other matching or
      simulation. Mice are more sensitive to pain after watching other mice experience
      pain; geese experience heart rate increases when seeing their mate in conflict;
      and infant macaques, chimpanzees, and humans automatically mimic adult facial
      expressions. In this article, we review findings in different species that
      illustrate how such reflexive processes are related to ("higher order") reflexive
      processes, such as cognitive empathy, theory of mind, and learning by imitation.
      We do so in the context of self-other matching in three different domains-in the
      motor domain (somatomotor movements), in the perceptual domain (eye movements and
      cognition about visual perception), and in the autonomic/emotional domain. We
      also review research on the developmental origin of these processes and their
      neural bases across species. We highlight gaps in existing knowledge and point
      out some questions for future research. We conclude that our understanding of the
      psychological and neural mechanisms of self-other mapping and other functions in
      our own species can be informed by considering the layered complexity these
      functions in other species.

PMID- 22866034
TI  - When Long-Range Zero-Lag Synchronization is Feasible in Cortical Networks.
AB  - Many studies have reported long-range synchronization of neuronal activity
      between brain areas, in particular in the beta and gamma bands with frequencies
      in the range of 14-30 and 40-80 Hz, respectively. Several studies have reported
      synchrony with zero phase lag, which is remarkable considering the synaptic and
      conduction delays inherent in the connections between distant brain areas. This
      result has led to many speculations about the possible functional role of zero
      lag synchrony, such as for neuronal communication, attention, memory, and feature
      binding. However, recent studies using recordings of single-unit activity and
      local field potentials report that neuronal synchronization may occur with non
      zero phase lags. This raises the questions whether zero-lag synchrony can occur
      in the brain and, if so, under which conditions. We used analytical methods and
      computer simulations to investigate which connectivity between neuronal
      populations allows or prohibits zero-lag synchrony. We did so for a model where
      two oscillators interact via a relay oscillator. Analytical results and computer
      simulations were obtained for both type I Mirollo-Strogatz neurons and type II
      Hodgkin-Huxley neurons. We have investigated the dynamics of the model for
      various types of synaptic coupling and importantly considered the potential
      impact of Spike-Timing Dependent Plasticity (STDP) and its learning window. We
      confirm previous results that zero-lag synchrony can be achieved in this
      configuration. This is much easier to achieve with Hodgkin-Huxley neurons, which
      have a biphasic phase response curve, than for type I neurons. STDP facilitates
      zero-lag synchrony as it adjusts the synaptic strengths such that zero-lag
      synchrony is feasible for a much larger range of parameters than without STDP.

PMID- 22866035
TI  - Is dorsal anterior cingulate cortex activation in response to social exclusion
      due to expectancy violation? An fMRI study.
AB  - People are typically quite sensitive about being accepted or excluded by others.
      Previous studies have suggested that the dorsal anterior cingulate cortex (dACC)
      is a key brain region involved in the detection of social exclusion. However,
      this region has also been shown to be sensitive to non-social expectancy
      violations. We often expect other people to follow an unwritten rule in which
      they include us as they would expect to be included, such that social exclusion
      likely involves some degree of expectancy violation. The present event-related
      functional magnetic resonance imaging (fMRI) study sought to separate the effects
      of expectancy violation from those of social exclusion, such that we employed an
      "overinclusion" condition in which a player was unexpectedly overincluded in the
      game by the other players. With this modification, we found that the dACC and
      right ventrolateral prefrontal cortex (rVLPFC) were activated by exclusion,
      relative to overinclusion. In addition, we identified a negative correlation
      between exclusion-evoked brain activity and self-rated social pain in the rVLPFC,
      but not in the dACC. These findings suggest that the rVLPFC is critical for
      regulating social pain, whereas the dACC plays an important role in the detection
      of exclusion. The neurobiological basis of social exclusion is different from
      that of mere expectancy violation.

PMID- 22866036
TI  - Coupling of voltage-sensors to the channel pore: a comparative view.
AB  - The activation of voltage-dependent ion channels is initiated by potential
      induced conformational rearrangements in the voltage-sensor domains that
      propagates to the pore domain (PD) and finally opens the ion conduction pathway.
      In potassium channels voltage-sensors are covalently linked to the pore via S4-S5
      linkers at the cytoplasmic site of the PD. Transformation of membrane electric
      energy into the mechanical work required for the opening or closing of the
      channel pore is achieved through an electromechanical coupling mechanism, which
      involves local interaction between residues in S4-S5 linker and pore-forming
      alpha helices. In this review we discuss present knowledge and open questions
      related to the electromechanical coupling mechanism in most intensively studied
      voltage-gated Shaker potassium channel and compare structure-functional aspects
      of coupling with those observed in distantly related ion channels. We focus
      particularly on the role of electromechanical coupling in modulation of the
      constitutive conductance of ion channels.

PMID- 22866038
TI  - Parenting and mental illness: a group for mothers.

PMID- 22866037
TI  - Beta Amyloid Differently Modulate Nicotinic and Muscarinic Receptor Subtypes
      which Stimulate in vitro and in vivo the Release of Glycine in the Rat
      Hippocampus.
AB  - Using both in vitro (hippocampal synaptosomes in superfusion) and in vivo
      (microdialysis) approaches we investigated whether and to what extent beta
      amyloid peptide 1-40 (Abeta 1-40) interferes with the cholinergic modulation of
      the release of glycine (GLY) in the rat hippocampus. The nicotine-evoked overflow
      of endogenous GLY in hippocampal synaptosomes in superfusion was significantly
      inhibited by Abeta 1-40 (10 nM) while increasing the concentration to 100 nM the
      inhibitory effect did not further increase. Both the Choline (Ch; alpha7 agonist;
      1 mM) and the 5-Iodo-A-85380 dihydrochloride (5IA85380, alpha4beta2 agonist; 10
      nM)-evoked GLY overflow were inhibited by Abeta 1-40 at 100 nM but not at 10 nM
      concentrations. The KCl evoked [(3)H]GLY and [(3)H]Acetylcholine (ACh) overflow
      were strongly inhibited in presence of oxotremorine; however this inhibitory
      muscarinic effect was not affected by Abeta 1-40. The effects of Abeta 1-40 on
      the administration of nicotine, veratridine, 5IA85380, and PHA543613
      hydrochloride (PHA543613; a selective agonist of alpha7 subtypes) on hippocampal
      endogenous GLY release in vivo were also studied. Abeta 1-40 significantly
      reduced (at 10 MUM but not at 1 MUM) the nicotine-evoked in vivo release of GLY.
      Abeta 1-40 (at 10 MUM but not at 1 MUM) significantly inhibited the PHA543613 (1
      mM)-elicited GLY overflow while was ineffective on the GLY overflow evoked by
      5IA85380 (1 mM). Abeta 40-1 (10 MUM) did not produce any inhibitory effect on
      nicotine-evoked GLY overflow both in the in vitro and in vivo experiments. Our
      results indicate that (a) the cholinergic modulation of the release of GLY occurs
      by the activation of both alpha7 and alpha4beta2 nicotinic ACh receptors (nAChRs)
      as well as by the activation of inhibitory muscarinic ACh receptors (mAChRs) and
      (b) Abeta 1-40 can modulate cholinergic evoked GLY release exclusively through
      the interaction with alpha7 and the alpha4beta2 nAChR nicotinic receptors but not
      through mAChR subtypes.

PMID- 22866039
TI  - Brain connectivity and mental illness.

PMID- 22866040
TI  - Air Pollution, Socioeconomic Status, and Children's Cognition in Megacities: The
      Mexico City Scenario.

PMID- 22866041
TI  - Calibration research: where do we go from here?
AB  - Research on calibration remains a popular line of inquiry. Calibration is the
      degree of fit between a person's judgment of performance and his or her actual
      performance. Given the continued interest in this topic, the questions posed in
      this article are fruitful directions to pursue to help address gaps in
      calibration research. In this article, we have identified six research directions
      that if productively pursued, could greatly expand our knowledge of calibration.
      The six research directions are: (a) what are the effects of varying the
      anchoring mechanisms from which calibration judgments are made, (b) how does
      calibration accuracy differ as a function of incentives and task authenticity,
      (c) how do students self-report the basis of their calibration judgments, (d) how
      do group interactions and social comparisons affect calibration accuracy, (e)
      what is the relation between absolute and relative accuracy, and (f) to what
      extent does calibration accuracy predict achievement? To help point the way to
      where we go from here in calibration research, we provide these research
      questions, propose research methods designed to address them, and identify prior,
      related studies that have shown promise in leading the way to fill these gaps in
      the literature.

PMID- 22866042
TI  - A simple statistic for comparing moderation of slopes and correlations.
AB  - Given a linear relationship between two continuous random variables X and Y that
      may be moderated by a third, Z, the extent to which the correlation rho is
      (un)moderated by Z is equivalent to the extent to which the regression
      coefficients beta(y) and beta(x) are (un)moderated by Z iff the variance ratio
      [Formula: see text] is constant over the range or states of Z. Otherwise,
      moderation of slopes and of correlations must diverge. Most of the literature on
      this issue focuses on tests for heterogeneity of variance in Y, and a test for
      this ratio has not been investigated. Given that regression coefficients are
      proportional to rho via this ratio, accurate tests, and estimations of it would
      have several uses. This paper presents such a test for both a discrete and
      continuous moderator and evaluates its Type I error rate and power under unequal
      sample sizes and departures from normality. It also provides a unified approach
      to modeling moderated slopes and correlations with categorical moderators via
      structural equations models.

PMID- 22866043
TI  - Psychosocial and psychophysiological effects of human-animal interactions: the
      possible role of oxytocin.
AB  - During the last decade it has become more widely accepted that pet ownership and
      animal assistance in therapy and education may have a multitude of positive
      effects on humans. Here, we review the evidence from 69 original studies on human
      animal interactions (HAI) which met our inclusion criteria with regard to sample
      size, peer-review, and standard scientific research design. Among the well
      documented effects of HAI in humans of different ages, with and without special
      medical, or mental health conditions are benefits for: social attention, social
      behavior, interpersonal interactions, and mood; stress-related parameters such as
      cortisol, heart rate, and blood pressure; self-reported fear and anxiety; and
      mental and physical health, especially cardiovascular diseases. Limited evidence
      exists for positive effects of HAI on: reduction of stress-related parameters
      such as epinephrine and norepinephrine; improvement of immune system functioning
      and pain management; increased trustworthiness of and trust toward other persons;
      reduced aggression; enhanced empathy and improved learning. We propose that the
      activation of the oxytocin system plays a key role in the majority of these
      reported psychological and psychophysiological effects of HAI. Oxytocin and HAI
      effects largely overlap, as documented by research in both, humans and animals,
      and first studies found that HAI affects the oxytocin system. As a common
      underlying mechanism, the activation of the oxytocin system does not only provide
      an explanation, but also allows an integrative view of the different effects of
      HAI.

PMID- 22866044
TI  - "What women like": influence of motion and form on esthetic body perception.
AB  - Several studies have shown the distinct contribution of motion and form to the
      esthetic evaluation of female bodies. Here, we investigated how variations of
      implied motion and body size interact in the esthetic evaluation of female and
      male bodies in a sample of young healthy women. Participants provided
      attractiveness, beauty, and liking ratings for the shape and posture of virtual
      renderings of human bodies with variable body size and implied motion. The
      esthetic judgments for both shape and posture of human models were influenced by
      body size and implied motion, with a preference for thinner and more dynamic
      stimuli. Implied motion, however, attenuated the impact of extreme body size on
      the esthetic evaluation of body postures, while body size variations did not
      affect the preference for more dynamic stimuli. Results show that body form and
      action cues interact in esthetic perception, but the final esthetic appreciation
      of human bodies is predicted by a mixture of perceptual and affective evaluative
      components.

PMID- 22866045
TI  - Social phenotypes of autism spectrum disorders and williams syndrome:
      similarities and differences.
AB  - Autism spectrum disorders (ASD) and Williams syndrome (WS) both are
      neurodevelopmental disorders, each with a unique social phenotypic pattern. This
      review article aims to define the similarities and differences between the social
      phenotypes of ASD and WS. We review studies that have examined individuals with
      WS using diagnostic assessments such as the Autism Diagnostic Observation
      Schedule (ADOS), cross-syndrome direct comparison studies, and studies that have
      individually examined either disorder. We conclude that (1) individuals with
      these disorders show quite contrasting phenotypes for face processing (i.e.,
      preference to faces and eyes) and sociability (i.e., interest in and motivation
      to interact with others), and (2) although the ADOS and a direct comparison study
      on pragmatic language ability suggest more deficits in ASD, individuals with WS
      are similarly impaired on social cognition and communicative skills. In light of
      these results, we discuss how cross-syndrome comparisons between ASD and WS can
      contribute to developmental theory, cognitive neuroscience, and the development
      and choice of clinical treatments.

PMID- 22866046
TI  - Momentary assessment of adults' physical activity and sedentary behavior:
      feasibility and validity.
AB  - INTRODUCTION: Mobile phones are ubiquitous and easy to use, and thus have the
      capacity to collect real-time data from large numbers of people. Research tested
      the feasibility and validity of an Ecological Momentary Assessment (EMA) self
      report protocol using electronic surveys on mobile phones to assess adults'
      physical activity and sedentary behaviors. METHODS: Adults (N = 110; 73% female,
      30% Hispanic, 62% overweight/obese) completed a 4-day signal-contingent EMA
      protocol (Saturday-Tuesday) with eight surveys randomly spaced throughout each
      day. EMA items assessed current activity (e.g., Watching TV/Movies,
      Reading/Computer, Physical Activity/Exercise). EMA responses were time-matched to
      minutes of moderate-to-vigorous physical activity (MVPA) and sedentary activity
      (SA) measured by accelerometer immediately before and after each EMA prompt.
      RESULTS: Unanswered EMA prompts had greater MVPA (+/-15 min) than answered EMA
      prompts (p = 0.029) for under/normal weight participants, indicating that
      activity level might influence the likelihood of responding. The 15-min.
      intervals before versus after the EMA-reported physical activity (n = 296
      occasions) did not differ in MVPA (p > 0.05), suggesting that prompting did not
      disrupt physical activity. SA decreased after EMA-reported sedentary behavior (n
      = 904 occasions; p < 0.05) for overweight and obese participants. As compared
      with other activities, EMA-reported physical activity and sedentary behavior had
      significantly greater MVPA and SA, respectively, in the +/-15 min of the EMA
      prompt (ps < 0.001), providing evidence for criterion validity. CONCLUSION:
      Findings generally support the acceptability and validity of a 4-day signal
      contingent EMA protocol using mobile phones to measure physical activity and
      sedentary behavior in adults. However, some MVPA may be missed among underweight
      and normal weight individuals.

PMID- 22866047
TI  - How positive affect modulates proactive control: reduced usage of informative
      cues under positive affect with low arousal.
AB  - An example of proactive control is the usage of informative cues to prepare for
      an upcoming task. Here the authors will present data from a series of three
      experiments, showing that positive affect along with low arousal reduces
      proactive control in form of a reduced reliance on informative cues. In three
      affect groups, neutral or positive affective picture stimuli with low and high
      arousal preceded every trial. In Experiments 1 and 2, using a simple response
      cueing paradigm with informative cues (66% cue validity), a reduced cue validity
      effect (CVE) was found under positive affect with low arousal. To test the
      robustness of the effect and to see whether reactive control is also modulated by
      positive affect, Experiment 3 used a cued task switching paradigm with
      predicitive cues (75% cue validity). As expected, a reduced CVE was again found
      specifically in the positive affect condition with low arousal, but only for task
      repetitions. Furthermore, there was no difference in switch costs between affect
      groups (with and without task cues). Taken together, the reduced CVE indicates
      that positive affect with low arousal reduces proactive control, while comparable
      switch costs suggest that there is no influence of positive affect on reactive
      control.

PMID- 22866049
TI  - The secrets of El Dorado viewed through a microbial perspective.
AB  - The formation of the Amazon Dark Earths was a model of sustainable soil
      management that involved intensive composting and charcoal (biochar) application.
      Biochar has been the focus of increasing research attention for carbon
      sequestration, although the role of compost or humic substances (HS) as they
      interact with biochar has not been much studied. We provide a perspective that
      biochar and HS may facilitate extracellular electron transfer (EET) reactions in
      soil, which occurs under similar conditions that generate the greenhouse gases
      methane and nitrous oxide. Facilitating EET may constitute a viable strategy to
      mitigate greenhouse gas emission. In general, we lack knowledge in the mechanisms
      that link the surface chemical characteristics of biochar to the physiology of
      microorganisms that are involved in various soil processes including those that
      influence soil organic matter dynamics and methane and nitrous oxide emissions.
      Most studies view biochar as a mostly inert microbial substrate that offers
      little other than a high sorptive surface area. Synergism between biochar and HS
      resulting in enhanced EET provides a mechanism to link electrochemical properties
      of these materials to microbial processes in sustainable soils.

PMID- 22866048
TI  - Interactions between Stress and Vestibular Compensation - A Review.
AB  - Elevated levels of stress and anxiety often accompany vestibular dysfunction,
      while conversely complaints of dizziness and loss of balance are common in
      patients with panic and other anxiety disorders. The interactions between stress
      and vestibular function have been investigated both in animal models and in
      clinical studies. Evidence from animal studies indicates that vestibular symptoms
      are effective in activating the stress axis, and that the acute stress response
      is important in promoting compensatory synaptic and neuronal plasticity in the
      vestibular system and cerebellum. The role of stress in human vestibular
      disorders is complex, and definitive evidence is lacking. This article reviews
      the evidence from animal and clinical studies with a focus on the effects of
      stress on the central vestibular pathways and their role in the pathogenesis and
      management of human vestibular disorders.

PMID- 22866050
TI  - The role of genes domesticated from LTR retrotransposons and retroviruses in
      mammals.
AB  - The acquisition of multiple genes from long terminal repeat (LTR)
      retrotransposons occurred in mammals. Genes belonging to a sushi-ichi-related
      retrotransposon homologs (SIRH) family emerged around the time of the
      establishment of two viviparous mammalian groups, marsupials and eutherians.
      These genes encode proteins that are homologous to a retrotransposon Gag capsid
      protein and sometimes also have a Pol-like region. We previously demonstrated
      that PEG10 (SIRH1) and PEG11/RTL1 (SIRH2) play essential but different roles in
      placental development. PEG10 is conserved in both the marsupials and the
      eutherians, while PEG11/RTL1 is a eutherian-specific gene, suggesting that these
      two domesticated genes were deeply involved in the evolution of mammals via the
      establishment of the viviparous reproduction system. In this review, we introduce
      the roles of PEG10 and PEG11/RTL1 in mammalian development and evolution, and
      summarize the other genes domesticated from LTR retrotransposons and endogenous
      retroviruses (ERVs) in mammals. We also point out the importance of DNA
      methylation in inactivating and neutralizing the integrated retrotransposons and
      ERVs in the process of domestication.

PMID- 22866051
TI  - The effect of standard heat and filtration processing procedures on antimicrobial
      activity and hydrogen peroxide levels in honey.
AB  - There is increasing interest in the antimicrobial properties of honey. In most
      honey types, antimicrobial activity is due to the generation of hydrogen peroxide
      (H(2)O(2)), but this can vary greatly among samples. Honey is a complex product
      and other components may modulate activity, which can be further affected by
      commercial processing procedures. In this study we examined honey derived from
      three native Australian floral sources that had previously been associated with
      H(2)O(2)-dependent activity. Antibacterial activity was seen in four red
      stringybark samples only, and ranged from 12 to 21.1% phenol equivalence against
      Staphylococcus aureus. Antifungal activity ranged from MIC values of 19-38.3%
      (w/v) against Candida albicans, and all samples were significantly more active
      than an osmotically equivalent sugar solution. All honey samples were provided
      unprocessed and following commercial processing. Processing was usually
      detrimental to antimicrobial activity, but occasionally the reverse was seen and
      activity increased. H(2)O(2) levels varied from 0 to 1017 MUM, and although
      samples with no H(2)O(2) had little or no antimicrobial activity, some samples
      had relatively high H(2)O(2) levels yet no antimicrobial activity. In samples
      where H(2)O(2) was detected, the correlation with antibacterial activity was
      greater in the processed than in the unprocessed samples, suggesting other
      factors present in the honey influence this activity and are sensitive to heat
      treatment. Antifungal activity did not correlate with the level of H(2)O(2) in
      honey samples, and overall it appeared that H(2)O(2) alone was not sufficient to
      inhibit C. albicans. We conclude that floral source and H(2)O(2) levels are not
      reliable predictors of the antimicrobial activity of honey, which currently can
      only be assessed by standardized antimicrobial testing. Heat processing should be
      reduced where possible, and honey destined for medicinal use should be retested
      post-processing to ensure that activity levels have not changed.

PMID- 22866052
TI  - Enhancing nitrification at low temperature with zeolite in a mining operations
      retention pond.
AB  - Ammonium nitrate explosives are used in mining operations at Diavik Diamond Mines
      Inc. in the Northwest Territories, Canada. Residual nitrogen is washed into the
      mine pit and piped to a nearby retention pond where its removal is accomplished
      by microbial activity prior to a final water treatment step and release into the
      sub-Arctic lake, Lac de Gras. Microbial removal of ammonium in the retention pond
      is rapid during the brief ice-free summer, but often slows under ice cover that
      persists up to 9 months of the year. The aluminosilicate mineral zeolite was
      tested as an additive to retention pond water to increase rates of ammonium
      removal at 4 degrees C. Water samples were collected across the length of the
      retention pond monthly over a year. The structure of the microbial community
      (bacteria, archaea, and eukarya), as determined by denaturing gradient gel
      electrophoresis of PCR-amplified small subunit ribosomal RNA genes, was more
      stable during cold months than during July-September, when there was a marked
      phytoplankton bloom. Of the ammonia-oxidizing community, only bacterial amoA
      genes were consistently detected. Zeolite (10 g) was added to retention pond
      water (100 mL) amended with 5 mM ammonium and incubated at 12 degrees C to
      encourage development of a nitrifying biofilm. The biofilm community was composed
      of different amoA phylotypes from those identified in gene clone libraries of
      native water samples. Zeolite biofilm was added to fresh water samples collected
      at different times of the year, resulting in a significant increase in laboratory
      measurements of potential nitrification activity at 4 degrees C. A significant
      positive correlation between the amount of zeolite biofilm and potential
      nitrification activity was observed; rates were unaffected in incubations
      containing 1-20 mM ammonium. Addition of zeolite to retention ponds in cold
      environments could effectively increase nitrification rates year-round by
      concentrating active nitrifying biomass.

PMID- 22866053
TI  - Meta-analysis of environmental impacts on nitrous oxide release in response to N
      amendment.
AB  - Atmospheric nitrous oxide (N(2)O) accounts for approximately 5% of the global
      greenhouse effect and destroys stratospheric ozone. Soils are the most important
      source of N(2)O, which is produced during nitrification and denitrification. To
      assess the impact of environmental variables and ecosystems on N(2)O flux, we
      performed a meta-analysis comparing N(2)O flux in N amended and matched control
      plots in non-agricultural soils. We found that N(2)O release increased with N
      amendment in the short term. Although there were few studies in shrubland, this
      ecosystem showed the greatest response. The N(2)O response to N amendment was
      greater in year-round studies and in studies with more measurements, but lower in
      longer studies. The N(2)O response was greater at higher latitudes and
      precipitation rates. We also observed an unexpected 55% decline in the N(2)O
      response to N amendment over the 23 years covered by the studies. This pattern
      may reflect a suppression of the N(2)O response from long-term N deposition
      accumulation, particularly in temperate regions. Although short term increases in
      reactive N entering natural systems may cause positive feedbacks to the release
      of N(2)O, this effect may diminish over time in locations with high rates of N
      deposition.

PMID- 22866054
TI  - Lymphotoxin-sensitive microenvironments in homeostasis and inflammation.
AB  - Stromal cell microenvironments within lymphoid tissues are designed to support
      immune cell homeostasis and to regulate ongoing immune responses to pathogens.
      Such stromal cell networks have been best characterized within lymphoid tissues
      including the spleen and peripheral lymph nodes, and systems for classifying
      stromal cell phenotypes and functions are emerging. In response to inflammation,
      stromal cell networks within lymphoid tissues change in order to accommodate and
      regulate lymphocyte activation. Local inflammation in non-lymphoid tissues can
      also induce de novo formation of lymphoid aggregates, which we term here
      "follicle-like structures." Of note, the stromal cell networks that underpin such
      follicles are not as well characterized and may be different depending on the
      anatomical site. However, one common element that is integral to the maintenance
      of stromal cell environments, either in lymphoid tissue or in extra-lymphoid
      sites, is the constitutive regulation of stromal cell phenotype and/or function
      by the lymphotoxin (LT) pathway. Here we discuss how the LT pathway influences
      stromal cell environments both in homeostasis and in the context of inflammation
      in lymphoid and non-lymphoid tissues.

PMID- 22866055
TI  - Modification of Seed Oil Composition in Arabidopsis by Artificial microRNA
      Mediated Gene Silencing.
AB  - Various post transcriptional gene silencing strategies have been developed and
      exploited to study gene function or engineer disease resistance. The recently
      developed artificial microRNA strategy is an alternative method of effectively
      silencing target genes. The Delta12-desaturase (FAD2), Fatty acid elongase
      (FAE1), and Fatty acyl-ACP thioesterase B (FATB) were targeted with amiR159b
      based constructs in Arabidopsisthaliana to evaluate changes in oil composition
      when expressed with the seed-specific Brassica napus truncated napin (FP1)
      promoter. Fatty acid profiles from transgenic homozygous seeds reveal that the
      targeted genes were silenced. The down-regulation of the AtFAD-2 gene
      substantially increased oleic acid from the normal levels of ~15% to as high as
      63.3 and reduced total PUFA content (18:2(Delta9,12) + 18:3(Delta9,12,15) +
      20:2(Delta11,14) + 20:3(Delta11,14,17)) from 46.8 to 4.8%. Delta12-desaturase
      activity was reduced to levels as low as those in the null fad-2-1 and fad-2-2
      mutants. Silencing of the FAE1 gene resulted in the reduction of eicosenoic acid
      (20:1(Delta11)) to 1.9 from 15.4% and silencing of FATB resulted in the reduction
      of palmitic acid (16:0) to 4.4% from 8.0%. Reduction in FATB activity is
      comparable with a FATB knock-out mutant. These results demonstrate for the first
      time amiR159b constructs targeted against three endogenous seed-expressed genes
      are clearly able to down-regulate and generate genotypic changes that are
      inherited stably over three generations.

PMID- 22866056
TI  - Unleashing the genome of brassica rapa.
AB  - The completion and release of the Brassica rapa genome is of great benefit to
      researchers of the Brassicas, Arabidopsis, and genome evolution. While its
      lineage is closely related to the model organism Arabidopsis thaliana, the
      Brassicas experienced a whole genome triplication subsequent to their divergence.
      This event contemporaneously created three copies of its ancestral genome, which
      had diploidized through the process of homeologous gene loss known as
      fractionation. By the fractionation of homeologous gene content and genetic
      regulatory binding sites, Brassica's genome is well placed to use comparative
      genomic techniques to identify syntenic regions, homeologous gene duplications,
      and putative regulatory sequences. Here, we use the comparative genomics platform
      CoGe to perform several different genomic analyses with which to study structural
      changes of its genome and dynamics of various genetic elements. Starting with
      whole genome comparisons, the Brassica paleohexaploidy is characterized, syntenic
      regions with A. thaliana are identified, and the TOC1 gene in the circadian
      rhythm pathway from A. thaliana is used to find duplicated orthologs in B. rapa.
      These TOC1 genes are further analyzed to identify conserved non-coding sequences
      that contain cis-acting regulatory elements and promoter sequences previously
      implicated in circadian rhythmicity. Each "cookbook style" analysis includes a
      step-by-step walk-through with links to CoGe to quickly reproduce each step of
      the analytical process.

PMID- 22866058
TI  - A Study Ex Vivo of the Effect of Epicardial Fat on the HeartLander Robotic
      Crawler.
AB  - A tethered epicardial crawling robot known as HeartLander has been developed for
      minimally-invasive surgery on the beating heart. The crawler has been tested in
      vivo many times in a porcine model, a model which provides generally authentic
      conditions in many ways; however, the pigs tested generally have little
      epicardial fat, whereas the epicardial fat in human patients will be
      considerable. As a result, it is necessary to determine the effect of such fat on
      the performance of the crawler. In one experiment, using fresh ovine hearts ex
      vivo, clogging of the suction chambers of the crawler during sliding over tissue
      with active suction was investigated for a variety of thicknesses of epicardial
      fat. In a second experiment, the maximum traction force during each step was
      measured when sliding with active suction repeatedly over the same location for a
      variety of fat thicknesses. The clogging experiment showed accumulation of fat in
      the suction chamber, with the amount dependent on the state of the epicardial
      membrane, but the suction line did not clog. The traction experiment showed that
      traction was maintained in all cases except when the epicardial membrane was
      excised completely.

PMID- 22866057
TI  - Gene Expression Profiling during Murine Tooth Development.
AB  - The aim of this study was to describe the expression of genes, including
      ameloblastin (Ambn), amelogenin X chromosome (Amelx), and enamelin (Enam) during
      early (pre-secretory) tooth development. The expression of these genes has
      predominantly been studied at post-secretory stages. Deoxyoligonucleotide
      microarrays were used to study gene expression during development of the murine
      first molar tooth germ at 24 h intervals, starting at the 11th embryonic day
      (E11.5), and up to the 7th day after birth (P7). The profile search function of
      Spotfire software was used to select genes with similar expression profile as the
      enamel genes (Ambn, Amelx, and Enam). Microarray results where validated using
      real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), and
      translated proteins identified by Western-blotting. In situ localization of the
      Ambn, Amelx, and Enam mRNAs were monitored from E12.5 to E17.5 using
      deoxyoligonucleotide probes. Bioinformatics analysis was used to associate
      biological functions with differentially expressed (DE; p <= 0.05) genes.
      Microarray results showed a total of 4362 genes including Ambn, Amelx, and Enam
      to be significant DE throughout the time-course. The expression of the three
      enamel genes was low at pre-natal stages (E11.5-P0) increasing after birth (P1
      P7). Profile search lead to isolation of 87 genes with significantly similar
      expression to the three enamel proteins. These mRNAs were expressed in dental
      epithelium and epithelium derived cells. Although expression of Ambn, Amelx, and
      Enam were lower during early tooth development compared to secretory stages
      enamel proteins were detectable by Western-blotting. Bioinformatic analysis
      associated the 87 genes with multiple biological functions. Around 35 genes were
      associated with 15 transcription factors.

PMID- 22866059
TI  - High-Energy Passive Mode-Locking of Fiber Lasers.
AB  - Mode-locking refers to the generation of ultrashort optical pulses in laser
      systems. A comprehensive study of achieving high-energy pulses in a ring cavity
      fiber laser that is passively mode-locked by a series of waveplates and a
      polarizer is presented in this paper. Specifically, it is shown that the
      multipulsing instability can be circumvented in favor of bifurcating to higher
      energy single pulses by appropriately adjusting the group velocity dispersion in
      the fiber and the waveplate/polarizer settings in the saturable absorber. The
      findings may be used as practical guidelines for designing high-power lasers
      since the theoretical model relates directly to the experimental settings.

PMID- 22866060
TI  - Scapula and humeral movement patterns and their relationship with pain: A
      preliminary investigation.
AB  - PURPOSE: Altered movement patterns may contribute to this shoulder pain following
      stroke. The purpose of this study was to examine scapular and humeral movement
      patterns in people with hemiparetic shoulder pain (HSP), and to explore the
      relationships between pain and these movement patterns.  METHODS: Kinematic data
      from nine participants with HSP and twelve matched controls were collected as
      they performed scapular plane shoulder elevation. Correlation analyses were used
      to examine relationships between participants' ratings of pain and kinematic
      data.  RESULTS: The HSP group had decreased humeral external rotation compared to
      the control group. Despite a trend toward decreased scapular upward rotation,
      there was considerable variation in scapular upward rotation movement patterns
      across the participants with HSP. Scapular tilt was not different between groups.
      There was an inverse relationship between pain and scapular upward rotation,
      indicating that those with more pain had less scapular upward rotation. 
      CONCLUSIONS: People with HSP demonstrated scapular and humeral movement patterns
      that differed from controls, where some of the altered movement patterns were
      related to reported pain levels. Rehabilitation management of people with HSP may
      be improved by careful assessment of scapulohumeral movement patterns and
      treatments aimed at normalizing these patterns.

PMID- 22866061
TI  - Culture Wires the Brain: A Cognitive Neuroscience Perspective.
AB  - There is clear evidence that sustained experiences may affect both brain
      structure and function. Thus, it is quite reasonable to posit that sustained
      exposure to a set of cultural experiences and behavioral practices will affect
      neural structure and function. The burgeoning field of cultural psychology has
      often demonstrated the subtle differences in the way individuals process
      information-differences that appear to be a product of cultural experiences. We
      review evidence that the collectivistic and individualistic biases of East Asian
      and Western cultures, respectively, affect neural structure and function. We
      conclude that there is limited evidence that cultural experiences affect brain
      structure and considerably more evidence that neural function is affected by
      culture, particularly activations in ventral visual cortex-areas associated with
      perceptual processing. 

PMID- 22866062
TI  - Understanding everyday life of morbidly obese adults-habits and body image.
AB  - BACKGROUND: Morbid obesity is a progressive, chronic condition associated with
      failed attempts at change and repeated relapses. AIM: There seems to be little
      previous research into the understanding of the everyday life of morbidly obese
      adults. We wanted to gain more knowledge about characteristics of eating habits
      and body image as well as motivational forces for change. METHODS: A qualitative
      approach was chosen in order to gain insight into how morbidly obese adults
      experience everyday life. Qualitative interviews are well suited to provide
      insight into themes from the interviewee's life story from the subjects' own
      perspectives. To gain insight into such processes, a narrative approach that
      allowed the informants to give voice to their ways of doing, thinking and feeling
      in daily life, was adopted. The informants comprised seven women and four men
      aged of 26-56 years, recruited from a population of obese individuals who had
      participated in a weight reduction course. A hermeneutic approach was used where
      the research question was the basis for a reflective interpretation. RESULTS: The
      following meaning-units were identified: to be perceived as overweight; and to
      see oneself as overweight. Ingrained habits: the struggle between knowing and
      doing; acting without knowing; and eating is soothing. CONCLUSIONS: Seeing
      oneself as an obese person is a gradual process that implied experiencing oneself
      as different from significant others, such as (slim) siblings and friends. To
      experience a gap between knowing and doing concerning food habits in everyday
      life indicates that informants value they have a choice. This is an important
      insight to consider when framing interventions to support this vulnerable group.

PMID- 22866063
TI  - Chemotherapy followed by chemoradiotherapy in locally advanced pancreatic cancer:
      A literature review and report of two cases.
AB  - The optimal treatment of patients with locally advanced pancreatic cancer remains
      to be elucidated. Chemo-radiotherapy is regarded as the treatment of choice, and
      studies have examined the sequential schedule of induction chemoradiotherapy
      followed by chemoradiotherapy, with favourable results. This study investigated
      the principal clinical trials of chemoradiotherapy treatment in locally advanced
      pancreatic cancer in 2 patients. The 2 patients received induction chemotherapy
      with gemcitabine 1000 mg/mq day on days 1 and 8 of a 21-day cycle for two cycles,
      followed by chemoradiotherapy with concurrent radiosensitizer bi-weekly
      gemcitabine 50 mg/mq for six weeks. Radiotherapy consisted of an external
      conformational 3D treatment administered to the pancreatic bed and locoregional
      nodes, with a total dose of 4500 Gy fractionated in 180 Gy/day, and a boost of
      900 Gy to the neoplastic mass. Efficacy was evaluated four weeks after the end of
      treatment by a computed tomography (CT) scan and by fluorodeoxyglucose positron
      emission tomography/CT. The patients underwent further treatment with periodical
      instrumental evaluation. A disease control rate was observed in the two patients
      following sequential treatment, enhanced by subsequent treatment. The two
      patients remained alive 23-24 months following the diagnosis. The sequential
      treatment schedule therefore was an effective option in our locally advanced
      pancreatic cancer patients. A phase III trial and further investigation are
      required to verify this option in clinical practice.

PMID- 22866064
TI  - Pathological complete response of colorectal liver metastases following
      chemotherapy with S-1 and oxaliplatin (SOX) in combination with bevacizumab: A
      case report.
AB  - Pathological complete response to systemic chemotherapy is associated with more
      favorable survival in patients with colorectal cancer liver metastases. We
      present a case of a 63-year-old man with multiple liver metastases from
      descending colon cancer. Following surgical resection of the primary tumor, the
      patient received systemic chemotherapy with S-1 and oxaliplatin in combination
      with bevacizumab. On achievement of a markedly favorable response to
      chemotherapy, surgical treatment of liver metastases was performed, and the liver
      tumors were successfully resected without any macroscopic residue.
      Histopathological analyses showed necrotic tissue in the complete absence of
      residual viable tumor cells. This is the first reported case of a patient with
      multiple liver metastases from descending colorectal cancer to achieve a
      pathological complete response following systemic chemotherapy with S-1 and
      oxaliplatin in combination with bevacizumab. This regimen is a systemic
      chemotherapy option to 'cure' liver metastasis from colorectal cancer.

PMID- 22866065
TI  - Gastric Ewing sarcoma/primitive neuroectodermal tumor: A case report.
AB  - Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) may arise in bone or
      soft tissue; however, these tumors rarely originate in the stomach. To the best
      of our knowledge, only four cases have previously been reported in the English
      language literature. A 41-year-old Japanese woman was admitted with abdominal
      pain and underwent gastrectomy to remove the primary tumor. Immunohistochemistry,
      chromosomal karyotype and molecular analysis using reverse transcription
      polymerase chain reaction were performed in the tumor specimens obtained. Tumor
      cells showed positive immunoreactivity for CD99, vimentin, CD117 (c-kit), S100,
      chromogranin A and synaptophysin. The tumor was a gastric ES/PNET with the EWS
      FLI1 fusion gene translocation t(11;22)(q24;q12). Multiple repeat
      metastasectomies, as well as multi-agent chemotherapy and radiotherapy were
      performed for recurrent disease. Despite treatment, the patient succumbed due to
      progressive disease 110 months after the initial surgery for gastric ES/PNET. A
      review of the reported cases suggests that patients with gastric ES/PNETs have an
      unfavorable prognosis following resection due to the high propensity of these
      tumors to metastasize. Thus, multimodal treatment approaches including surgery,
      as well as multi-agent chemotherapy and radiotherapy may provide a survival
      benefit for patients with gastric ES/PNETs.

PMID- 22866066
TI  - Serotonin synthesis and metabolism-related molecules in a human prostate cancer
      cell line.
AB  - Prostate cancer is one of the most common tumors in males and its incidence is
      steadily increasing worldwide. Serotonin or 5-hydroxytryptamine (5-HT) is a well
      known neurotransmitter that mediates a wide variety of physiological effects. An
      increase in the number of 5-HT-releasing neuroendocrine (NE) cells has been
      correlated with tumor progression. However, it is particularly unclear whether
      released 5-HT or the release of 5-HT has a role in tumor cell growth. We
      hypothesized that 5-HT synthesis and metabolism in NE cells regulate the growth
      of prostate cancer cells. In the present study, 5-HT was found to play a role as
      a cell growth factor in prostate cancer cells. Moreover, the pharmacological
      inhibition of 5-HT synthesis and metabolism interrupted the growth of prostate
      cancer cells. To confirm the existence of 5-HT in prostate cancer cells, we
      performed ELISA, HPLC, RT-PCR and immunohistochemical analyses. A high expression
      of tryptophan hydroxylase (TPH-1), dopa decarboxylase (DDC) and monoamine oxidase
      A (MAO-A) was noted in the prostate cancer cells when compared with normal
      prostate cells. Previous studies showed that 5-HT stimulated the proliferation of
      prostate cancer cells mediated by 5-HT receptors 5-HTR1A and R1B. However, cell
      proliferation was significantly inhibited when siRNA for both DDC and TPH-1 was
      transfected to the cells. Consequently, we propose that the secretion system of
      prostate NE cells capable of 5-HT synthesis and metabolism plays a significant
      role in prostate tumor generation and progression. These findings provide crucial
      clues for the development of potential pharmacotherapeutics to slow prostate
      tumor progression.

PMID- 22866067
TI  - Clinicopathological and patient characteristics of early gastric neoplasia
      endoscopically resected with loss of Mlh1 expression.
AB  - Hypermethylation of the promoter region of the MLH1 gene leads to loss of Mlh1
      protein expression and plays a key role in the development of gastric cancer.
      Little is known about the association between Mlh1 expression and the
      clinicopathological and patient characteristics in early gastric neoplasia,
      particularly in endoscopically resected tumors. Immunohistochemistry was used to
      examine Mlh1 expression in 140 early gastric neoplasias obtained by endoscopic
      resection and comprising 31 gastric adenomas (GAs) and 109 early gastric cancers
      (EGCs), and compared them to corresponding clinicopathological and patient data.
      P53 expression and phenotypic profiles were also analyzed. The rate of reduced
      Mlh1 expression and P53 overexpression was 9.6 and 6.5% in GAs, and 27.5 and
      27.5% in EGCs, respectively. In elderly patients (>=65 years of age), the
      aberrant expression of Mlh1 in EGCs was more significant in female than in male
      patients (59.9 vs. 29.8%; P=0.016). In addition, the frequency of aberrant Mlh1
      expression in EGCs increased significantly in patients with oncological family
      histories and elevated gross type (P=0.033 and P=0.04, respectively). Moreover, a
      significant correlation was observed among aberrant Mlh1, P53-negative and HGM
      expression. The present findings suggest that loss of Mlh1 expression is
      associated with age, gender, oncological family history and tumor growth pattern
      in EGC. Patient and tumor characteristics are key factors in the screening,
      surveillance and diagnosis of early gastric neoplasia, particularly in elderly
      individuals.

PMID- 22866068
TI  - Ductal carcinoma in situ arising within a benign phyllodes tumor: A case report
      with a review of the literature.
AB  - Phyllodes tumor (PT) is a rare type of breast tumor that rarely occurs with
      breast carcinoma. This study evaluated a 53-year-old female patient with a benign
      PT with ductal carcinoma in situ (DCIS) within the tumor. A firm, painless, well
      demarcated tumor measuring 4-5 cm was noted in the left breast. Over the course
      of the previous 14 years, the patient underwent excision of a breast tumor four
      times at the same site in the left breast. The pathological diagnosis of the
      first tumor was a fibroadenoma (FA), and those of the following three were benign
      PTs. The tumor was the 5th one noted over the course of the previous 14 years,
      following the previously recorded surgeries. A firm tumor with a diameter of 3.5
      cm was located beneath the scar from the previous surgery, just above the nipple
      of the left breast. Mammography revealed a high-density irregularly shaped mass
      with a clear margin. An ultrasound showed low but heterogeneous echogenicity. A
      computed tomography scan revealed a well-defined enhanced tumor. These image
      examinations were compatible with recurrent PT. Fine-needle aspiration cytology
      revealed that the tumor was likely a benign FA. The patient underwent a partial
      mastectomy with a 1.0 cm margin from the tumor edge, and the firm, attached scar
      tissue was also resected. Macroscopic examination showed a hard elastic mass,
      which was encapsulated by thin fibrous tissue and which adhered firmly to the
      adjacent scar tissue. Microscopic examination showed a 5 mm in diameter DCIS of
      the cribiform type in a section of the PT epithelial component with an apparently
      benign stroma. The DCIS cells were strongly positive for estrogen and
      progesterone receptors, but HER2 expression was negative (score 0). The patient
      received local irradiation following surgery and no evidence of recurrence or
      metastasis was detected in the 2 years following surgery. This was a noteworthy
      case of a DCIS arising in benign PT. To the best of our knowledge, a total of 28
      breast carcinomas were previously reported to arise in PT. In this case report, a
      female patient who presented with a PT was evaluated. A review of the literature
      is also discussed.

PMID- 22866069
TI  - Novel immunohistochemical marker, integrin alpha(V)beta(3), for BOP-induced early
      lesions in hamster pancreatic ductal carcinogenesis.
AB  - N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic ductal carcinomas and
      early ductal lesions in Syrian hamsters have been reported to show
      histopathological resemblance to those in humans. Specific protein expression
      profiles have been found in human carcinomas, but a detailed molecular approach
      regarding the dissection of BOP-induced pancreatic carcinogenesis has yet to be
      determined. The present immunohistochemical study of early and advanced hamster
      lesions focused on five proteins reported to be overexpressed in human patients,
      to clarify interspecies phenotype similarity. Integrin alpha(V)beta(3) was found
      to be overexpressed in the epithelial cells of 13 of 14 atypical hyperplasias and
      6 of 6 adenocarcinomas. This overexpression was more frequent than in the
      remaining four proteins. However, immunoreactivity for alpha-enolase in
      epithelial cells and for kallikrein 7 and galectin-1/3 in both epithelial and
      stromal cells was also evident at various frequencies. Thus, similarities of
      tumor-associated protein expression between human and hamster pancreatic ductal
      lesions were confirmed, and integrin alpha(V)beta(3) was identified as a
      potentially useful immunohistochemical marker for early lesions in hamsters.

PMID- 22866070
TI  - Serum concentration and expression of Reg IV in patients with esophageal cancer:
      Age-related elevation of serum Reg IV concentration.
AB  - Regenerating islet-derived family, member 4 (REG4, which encodes Reg IV) is a
      marker for cancer and inflammatory bowel disease. This study aimed to investigate
      the diagnostic utility of Reg IV measurement in sera from esophageal cancer
      patients. Reg IV expression was examined in 269 esophageal cancer samples by
      immunostaining and the Reg IV levels in sera were measured from 65 patients with
      esophageal squamous cell carcinoma (SCC) by enzyme-linked immunosorbent assay. No
      Reg IV staining was detected in 255 SCC and 4 small cell carcinoma samples,
      whereas Reg IV was stained in 4 of 10 (40%) adenocarcinoma samples. Serum Reg IV
      concentration in esophageal SCC patients was significantly higher compared to
      that of the control subjects (P=0.0003). A significant correlation between serum
      Reg IV concentration and age was found in control subjects (P<0.0001). When serum
      Reg IV concentration was analyzed according to age, the distribution of serum Reg
      IV concentration in patients with esophageal SCC was similar to that of the
      control subjects. These results suggest that Reg IV expression is highly specific
      for adenocarcinoma of the esophagus. Further investigation is required to clarify
      whether Reg IV serves as a serum tumor marker for esophageal cancer.

PMID- 22866071
TI  - Irinotecan monotherapy offers advantage over combination therapy with irinotecan
      plus cisplatin in second-line setting for treatment of advanced gastric cancer
      following failure of fluoropyrimidine-based regimens.
AB  - The optimal regimen of chemotherapy for gastric cancer in a second-line setting
      remains to be clarified. The aim of this retrospective study was to evaluate the
      efficacy and safety of second-line irinotecan treatment. A total of 134 patients
      with gastric cancer who had received prior chemotherapy with fluoropyrimidine
      based regimens were treated with irinotecan (150 mg/m(2) on days 1 and 15) alone
      every 4 weeks (Arm I) or irinotecan (70 mg/m(2) on days 1 and 15) plus cisplatin
      (80 mg/m(2) on day 1) every 4 weeks (Arm IP) between April, 2004 and March, 2009.
      Patient characteristics, response rate, progression-free survival, overall
      survival and safety were investigated. Of 134 patients with recurrent or
      unresectable gastric cancer, 92 were treated in Arm I and 42 patients in Arm IP.
      Overall response rate in Arm I was 8.1%, compared with 20.0% in Arm IP (P=0.65).
      Median progression-free survival (Arm I vs. IP; 2.6 vs. 2.7 months, P=0.73) and
      median overall survival (Arm I vs. IP; 9.8 vs. 8.0 months, P=0.67) did not differ
      between the two treatment groups. Neutropenia, leukopenia and anorexia were the
      most common grade 3/4 adverse events, occurring significantly more frequently in
      Arm IP than in Arm I (P<0.05). Irinotecan may be a key agent, and serial
      irinotecan monotherapy is more beneficial as compared to irinotecan plus
      cisplatin in the treatment of advanced gastric cancer in second-line settings.
      Irinotecan monotherapy is beneficial compared to irinotecan plus cisplatin in
      second-line settings for the treatment of advanced gastric cancer refractory to
      fluoropyrimidine-based regimens.

PMID- 22866072
TI  - Availability of irinotecan in a second-line setting confers survival benefit to
      patients with advanced gastric cancer refractory to fluoropyrimidine-based
      regimens.
AB  - Optimal second-line chemotherapy may contribute to favorable survival in patients
      who receive first-line treatment for advanced gastric cancer. The aim of this
      retrospective study was to compare a second-line setting using irinotecan with
      paclitaxel in terms of survival benefit and safety. A total of 179 patients with
      recurrent or unresectable gastric cancer who had received prior chemotherapy with
      a fluoropyrimidine-based regimen were treated with irinotecan alone at 150
      mg/m(2) on days 1 and 15 every 4 weeks (Cohort I) or weekly paclitaxel at 80
      mg/m(2) on days 1, 8 and 15 every 4 weeks (Cohort P) between April, 2004 and
      March, 2009. Patient characteristics, overall response rate, disease control
      rate, progression-free survival, overall survival and safety were investigated.
      Of the 179 patients, 92 received irinotecan and 87 patients who were
      contraindicated for irinotecan received weekly paclitaxel. The overall response
      and disease control rates in Cohort I were 6.5 and 43.5%, respectively, as
      compared with 9.8 and 54.9%, respectively, in Cohort P. No variation was noted in
      median progression-free survival (Cohort I vs. P, 2.6 vs. 2.8 months; P=0.812),
      whereas median overall survival (Cohort I vs. P, 9.8 vs. 4.9 months; P<0.0001)
      differed significantly between the two cohorts. The most common grade 3/4 adverse
      events were neutropenia, leukopenia, anemia and anorexia, which were tolerable in
      each treatment cohort. Availability of irinotecan in a second-line setting
      confers a survival benefit to advanced gastric cancer patients in whom
      fluoropyrimidine-based first-line chemotherapy was unsuccessful.

PMID- 22866073
TI  - Association between brain natriuretic peptide and distant metastases in advanced
      non-small cell lung cancer patients.
AB  - This study aimed to investigate the relationship between clinicopathological
      factors and plasma brain natriuretic peptide (BNP) levels in non-small cell lung
      cancer (NSCLC) patients. A total of 133 patients with advanced NSCLC were
      included in this study. The level of BNP was determined at the time of diagnosis.
      The BNP plasma concentration was measured using a chemiluminescent enzyme
      immunoassay kit. The univariate relationship between each independent
      clinicopathological variable and plasma BNP was examined using the Chi-square
      test. The survival curves were determined using the Kaplan-Meier method.
      According to the cut-off value of plasma BNP levels (11.5 and 22.4 pg/ml), plasma
      BNP negatively correlated with the presence of metastases (Chi-square test,
      p=0.0374 and p=0.0098, respectively). However, no significant association between
      patient survival time and plasma BNP levels was found. Reduced plasma BNP levels
      in advanced NSCLC patients with metastases were noted and the possibility was
      raised that BNP decreases distant metastases of advanced NSCLC patients.

PMID- 22866074
TI  - Detection of MET and SOX2 amplification by quantitative real-time PCR in non
      small cell lung carcinoma.
AB  - Non-small cell lung carcinoma is a leading cause of cancer-related death.
      Amplification of the two oncogenes MET and SOX2 is frequently encountered in non
      small-cell lung carcinoma. This study aimed to use real-time quantitative PCR to
      assess the correlation of MET and SOX2 amplification with clinicopathological
      factors. This study was conducted using 115 tissue samples including 57 squamous
      cell carcinomas (SCCs), 50 adenocarcinomas (ADCs) and 8 adenosquamous carcinomas
      (ADSCs). A total of 67 patients (58.3%) had a history of smoking. Our results
      showed that the frequency of MET amplification in SCCs was significantly higher
      compared to ADCs (chi(2)=8.0, P=0.005). SOX2 showed a markedly preferential
      amplification in SCCs compared to ADCs in the smoking group cases (P=0.014).
      Lymph node invasion correlated with MET amplification in SCCs marginally more
      significantly compared to ADCs (P=0.02). The amplified MET occurred more
      frequently in SCCs compared to ADCs correlated to tumor dimension at a small
      scale (<5 cm) (P=0.01). No significant difference in SOX2 amplification was found
      with regards to lymph node metastasis or tumor dimension. SOX2 and MET
      amplifications were not associated with gender or age. However, MET amplification
      in SCCs among patients younger than 64 years of age was higher compared to ADCs
      and ADSCs (P=0.03). Among ADSCs, MET was not amplified among patients who had
      never been smokers or were younger than 64 years of age. Neither MET nor SOX2
      were amplified in tumors with dimensions <5 cm and without lymph node invasion.
      Findings of this study showed that MET and SOX2 amplifications are more common in
      the SCCs of smokers. Moreover, MET amplification is intrinsic in SCCs
      particularly among smokers, with regards to tumor growth, lymph node invasion and
      negative correlation to SOX2 amplification. The incidence of discrepancy in the
      amplifications of MET and SOX2 in SCCs and ADCs suggests that the MET and SOX2
      genes play different roles in SCC and ADC tumorigenesis, respectively,
      particularly among smokers.

PMID- 22866075
TI  - Screen and analysis of key disease genes for precancerous lesions of oral buccal
      mucosa induced by DMBA in golden hamsters.
AB  - 7,12-Dimethylbenz(a)-anthracene (DMBA)-induced oral buccal mucosa squamous cell
      carcinoma in Syrian golden hamsters was used to establish precancerous lesions.
      Agilent rat whole-genome microarray and biological information analysis were used
      to screen for genes related to key diseases during the transformation of normal
      buccal mucosa to precancerous lesions in golden hamsters. DMBA acetone solution
      (0.5%) was used to establish a model of precancerous lesions in oral buccal
      mucosa in golden hamsters. The results showed that a total of 1331 genes were
      differentially expressed, including 1278 known, 53 unknown, 747 up-regulated and
      584 down-regulated genes. Analysis revealed a total of 14 gene interaction
      pathways that significantly associated with the 1278 known differentially
      expressed genes (P<0.05). In conclusion, the occurrence of precancerous lesions
      in the oral buccal mucosa of golden hamsters was caused by a number of genetic
      changes that resulted in changes to their respective pathways. Key candidate
      genes for the formation of precancerous lesions in oral buccal mucosa included
      Cyp2b13, Orc1L, casp8, CCL5, CXCL12, CCL20, Serping1, P518/Qrfp, F5, TFPI, Vcam1,
      Fn1, Angpt2, Lcp2, Cxadr, Lyn, Hck, Btk, RGD1564385/fes, Vav1 and IL5ra.

PMID- 22866076
TI  - Complex translocation involving four chromosomes in a novel Philadelphia-positive
      chronic myeloid leukemia case.
AB  - The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic
      myeloid leukemia (CML) cases. Approximately 5-10% of these patients show complex
      translocations involving a third chromosome in addition to chromosomes 9 and 22.
      Since the majority of CML cases are currently treated with imatinib, variant
      rearrangements in general have no specific prognostic significance, although the
      mechanisms involved in resistance to therapy have yet to be investigated. This
      study evalutated a CML case with complex chromosomal aberrations not previously
      observed. A four chromosome translocation involving chromosomal regions such as
      12q24.2-24.31 and 16p11.2 besides 9q34 and 22q11 were characterized in detail by
      array-proven multicolor banding (aMCB). A beneficial response to imatinib was
      noted in the patient.

PMID- 22866077
TI  - Factors associated with the misdiagnosis of sentinel lymph nodes using touch
      imprint cytology for early stage breast cancer.
AB  - Accurate intraoperative diagnosis of sentinel node metastasis enables the surgeon
      to make an immediate decision to proceed to axillary lymph node dissection
      (ALND), thereby avoiding the economic and psychological costs of a second
      operation. The present study aimed to evaluate the clinical value of touch
      imprint cytology (TIC) and investigate the potential factors associated with
      misdiagnosis. A total of 366 patients with Tis-T2 breast carcinoma were included
      after undergoing successful sentinel lymph node biopsy (SLNB). TIC was routinely
      performed intraoperatively, and the results were compared with definitive
      histological assessments of serial sections (SS) with hematoxylin and eosin (H&E)
      staining. A total of 992 SLNs from 366 patients were used in the study. Based on
      the final histological diagnosis, the sensitivity, specificity and overall
      accuracy of TIC was 76.6, 98.8 and 92.3%, respectively, on a per patient basis,
      and 79.9, 98.9 and 96.1%, respectively, on a per node basis. TIC was
      significantly more sensitive for macrometastasis than micrometastasis (80.0 vs.
      28.6%, P<0.01). Of 9 total 'false positives', 3 were due to micrometastasis which
      were not identified by serial section with H&E staining, 4 were actual false
      positives which were due to interpretation error, and 2 were due to sampling
      error. The majority of the false-negatives (28 of 30 SLNs) were due to
      micrometastasis in the SLNs (sampling error). In conclusion, TIC is feasible for
      clinical use and is able to detect macrometastasis in the SLNs of early stage
      invasive breast cancer patients with an acceptable accuracy while its ability to
      detect micrometastasis is limited.

PMID- 22866078
TI  - Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is
      mediated by tumor-associated specific growth factors.
AB  - Neural and mesenchymal stem cells have extensive tropism for malignant glioma.
      The tumor tropism of induced pluripotent stem (iPS) cells was tested using the
      Matrigel invasion assay. Mouse iPS cells showed a significant tropism to the
      conditioned media prepared from six rodent and human glioma cell lines and this
      tropism to the glioma conditioned media was partially blocked by the neutralizing
      antibodies for four major tumor-associated growth factors [stem cell factor
      (SCF), platelet-derived growth factor BB (PDGF-BB), stromal-derived factor-1alpha
      (SDF-1alpha) and vascular endothelial growth factor (VEGF)], which are secreted
      from the malignant gliomas. The tropism of the iPS cells was enhanced by the
      growth factors in a concentration-dependent manner from 0.1 to 100 ng/ml. The
      receptors for those growth factors (c-Kit, ICAM-1, CXCR4 and VEGFR2), measured by
      reverse transcriptase-polymerase chain reaction, were highly up-regulated in the
      mouse iPS cells compared to the mouse fibroblasts. The results showed that the
      specific growth factors secreted from the gliomas strongly attracted the iPS
      cells. Therefore, gene therapies using iPS cells as vectors to deliver anti-tumor
      agents are novel strategies for the treatment of malignant gliomas that deeply
      infiltrate the brain.

PMID- 22866079
TI  - Therapy of Hodgkin's lymphoma in clinical practice: A retrospective long-term
      follow-up analysis.
AB  - Treatment of Hodgkin's lymphoma (HL) is perceived to be relatively
      straightforward. Consequently, patients are not usually referred to hemato
      oncologically specialized centres and are treated locally instead. Comprehensive
      findings beyond prospective controlled trials are therefore lacking. Clinical
      data of 209 patients who had received a HL diagnosis were collected. A total of 7
      patients received radiotherapy (RT) alone (3%), 75 (35%) were treated with a
      combination of chemotherapy (CT) and RT and 127 patients received CT alone
      [mainly doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)]. Complete
      response (CR) following first-line treatment was achieved in 178 patients (85%)
      and in 195 (93%) after salvage treatment. Favorable disease (p=0.000359), limited
      stage disease (p=0.0003), involvement of lymph nodes above the diaphragm (p=0.05)
      and absence of mediastinal bulky tumor involvement positively affected the CR
      rate following first-line treatment. Out of the 195 patients that achieved CR, 31
      relapsed. Male gender (p=0.043) and age over 45 years (p=0.047) were
      significantly associated with an increased incidence of relapse. Age at diagnosis
      was the key factor affecting long-term outcome. The event-free survival (EFS)
      projected at 120 months was 80 and 57% for patients younger and older than 45
      years, respectively (p=0.022). The overall survival (OS) projected at 120 months
      was 92 and 38% for patients younger and older than 45 years, respectively
      (p=0.00561). A second neoplasia was diagnosed in 8 patients. The development of a
      tumor in 4 cases (breast, lung and thyroid cancer) was likely RT-related. Only 1
      patient not receiving RT developed acute myeloid leukemia. The EFS and OS of the
      141 early-stage patients treated with CT + RT (n=62) or with CT alone (n=79) were
      not statistically different.

PMID- 22866080
TI  - Thymidylate synthetase and dihydropyrimidine dehydrogenase mRNA levels in
      esophageal cancer.
AB  - This study investigated the mRNA levels of thymidylate synthetase (TYMS) and
      dihydropyrimidine dehydrogenase (DPYD) in esophageal squamous cell carcinoma
      (ESCC). TYMS and DPYD gene expression was quantified using real-time RT-PCR in 56
      patients with ESCC, co-amplified with glyceraldehyde-3-phosphate dehydrogenase as
      an internal standard. The results were analyzed with reference to the
      clinicopathological characteristics and the prognosis of the ESCC patients. The
      TYMS and DPYD expression levels in patients positive with lymphatic invasion were
      significantly higher compared to those in patients who exhibited negative
      lymphatic invasion (TYMS P=0.0127, DPYD P=0.0127). Patients were classified into
      the groups high TYMS/DPYD, high TYMS but low DPYD, low TYMS but high DPYD and low
      TYMS/DPYD. The highest survival rate was found in the group with low TYMS/DPYD
      and the lowest survival rate in the group with high TYMS/DPYD (P=0.017). It was
      concluded that, on the basis of the multivariate analysis, TYMS mRNA expression
      is a candidate that serves as an independent prognostic factor for ESCC patients.

PMID- 22866081
TI  - Shift in cytotoxic target from estrogen receptor-positive to estrogen receptor
      negative breast cancer cells by trastuzumab in combination with taxane-based
      chemotherapy.
AB  - Trastuzumab has shown significant clinical benefits in patients with operable and
      metastatic HER2-positive breast cancer. However, the biological mechanism of the
      additional effect of trastuzumab administered in combination with conventional
      chemotherapy is poorly understood. We performed a retrospective analysis of 55
      patients with HER2-positive breast cancer treated with anthracycline and taxane
      (chemotherapy alone; CT), or trastuzumab in combination with taxane-based
      chemotherapy (CT+T) for neoadjuvant chemotherapy. We determined the therapeutic
      efficacies [clinical (CR) and pathological complete responses (pCR)] and changes
      in the proportion of positive cells for each biomarker pre- to post-neoadjuvant
      chemotherapy for each treatment regimen. Clinical-CR and quasi-pCR rates defined
      as the absence of invasive tumors or only a few remaining invasive tumor cells
      were 6.9 and 31.0% in the CT group and 46.2 and 65.4% in the CT+T group,
      respectively. In the CT group, the proportion of estrogen receptor (ER)
      /progesterone receptor (PgR)-positive cells decreased significantly following
      treatment (ER, 73.5 vs. 50.9%; P=0.02). Changes in the proportion of ER-/PgR
      positive cells were not noted in the CT+T group (ER, 81.9 vs. 80.3%; P=0.61),
      although a relatively greater decrease in the proportion of Ki-67-positive cells
      was found in the CT+T group than that in the CT group (-26.5 vs. -13.7%). These
      findings indicate that CT+T inhibits ER-negative and Ki-67-positive breast cancer
      cells. In conclusion, trastuzumab sensitized ER-negative proliferative cells to
      cytotoxic chemotherapy. This finding may indicate an additional clinical effect
      of trastuzumab when administered in combination with conventional chemotherapy as
      neoadjuvant chemotherapy for HER2-positive breast cancer.

PMID- 22866082
TI  - Identification of responders/non-responders to 5-fluorouracil based on individual
      50% inhibitory area under the concentration curve of 5-fluorouracil obtained with
      collagen gel droplet-embedded culture-drug sensitivity test in colorectal cancer.
AB  - We previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells
      obtained from colorectal cancer (CRC) patients using the collagen gel droplet
      embedded culture-drug sensitivity test (CD-DST). Multiple drug concentrations and
      contact durations, and the area under the concentration curve (AUC) and growth
      inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was
      approximated to the logarithmic curve. Moreover, the individualized AUC(IR50),
      the AUC value which gives 50% growth inhibition, was calculated using the AUC-IR
      curve. This study aimed to identify responders/non-responders to 5-FU based on
      the individual AUC(IR50) obtained with CD-DST in order to establish
      individualized chemotherapy for CRC patients. The individual AUC(IR50) was
      calculated from each AUC-inhibition rate regression curve in all patients using
      the CD-DST. The cumulative distribution of the individual AUC(IR50) in CRC
      patients was evaluated. The cumulative distribution of the individual AUC(IR50)
      was regressed over the sigmoid curve (logarithmic scale). The approximate
      expression was almost exactly y=ab^exp(-cx) (a=0.9739, b=1.7096E-21, c=0.8990,
      the sum of square residuals, 0.0279). In the 80 cases examined, no notable change
      was observed in the regression curve when the number of patients increased. A
      standard curve was obtained describing responders to 5-FU among all CRC patients.
      From this standard curve, we ascertained that non-responders accounted for
      approximately 5% of all patients. Moreover, we were able to classify responders
      into good or intermediate responders to 5-FU. The standard curve describing
      response to 5-FU in CRC patients offers a useful tool in the establishment of
      individualized chemotherapy.

PMID- 22866083
TI  - Retrospective analysis of metastatic sarcoma patients.
AB  - Numerous studies have reported the survival of metastatic sarcoma patients who
      have undergone either a lung metastasectomy or chemotherapy. However, little is
      known with regards to the clinical course of patients with bone or soft tissue
      sarcomas who have succumbed to disease. This study aimed to analyze the
      metastatic patterns of sarcoma patients and to describe the clinical course after
      the detection of distant metastasis. We reviewed the clinical records of 255
      patients with a diagnosis of sarcoma who were referred to our institution, and
      found 63 patients who succumbed due to metastasis. We examined the clinical
      features of the initially detected distant metastases, the subsequent clinical
      course up to the time of patient death and the survival time of patients who died
      of lung metastasis. Of the 63 patients who died of distant metastasis, 52 (83%)
      developed lung metastasis as the first metastatic site, while 22 (35%) developed
      extra-pulmonary metastasis. The majority (77%; 49 of 63 patients) died of primary
      metastasis. While all 18 bone sarcoma patients died of lung metastasis, 11 of the
      45 soft tissue sarcoma patients died of extra-pulmonary metastasis. Six patients
      died of brain metastasis. The survival of the patients with lung metastasis was
      only approximately 6 months following the cessation of treatment, regardless of
      the type of treatment used. These results indicate that planned follow-up and
      treatment of sarcomas require a precise knowledge of tumor clinical behavior,
      particularly of the preponderant activity.

PMID- 22866084
TI  - Fucoidan reduces the toxicities of chemotherapy for patients with unresectable
      advanced or recurrent colorectal cancer.
AB  - Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX)
      or irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) has become a standard
      regimen for advanced or recurrent colorectal cancer. Numerous studies have
      reported that long-term use of FOLFOX or FOLFIRI leads to better survival for
      these patients. Thus, control of the toxicity of these drugs may be crucial to
      prolonging survival. Fucoidan is one of the major sulfated polysaccharides of
      brown seaweeds and exhibits a wide range of biological activities. In the present
      study, we analyzed the effect of fucoidan on suppressing the toxicity of anti
      cancer drugs. A total of 20 patients with unresectable advanced or recurrent
      colorectal cancer scheduled to undergo treatment with FOLFOX or FOLFIRI were
      randomly allocated into a fucoidan treatment group (n=10) and a control group
      without fucoidan treatment (n=10). Results showed that fucoidan regulated the
      occurrence of fatigue during chemotherapy. Chemotherapy with fucoidan was
      continued for a longer period than chemotherapy without fucoidan. Additionally,
      the survival of patients with fucoidan treatment was longer than that of patients
      without fucoidan, although the difference was not significant. Thus, fucoidan may
      enable the continuous administration of chemotherapeutic drugs for patients with
      unresectable advanced or recurrent colorectal cancer, and as a result, the
      prognosis of such patients is prolonged.

PMID- 22866085
TI  - Breast cancer patients in Libya: Comparison with European and central African
      patients.
AB  - The present study evaluated the incidence of breast cancer in Libya and described
      the clinicopathological and demographic features. These features were then
      compared with corresponding data from patients from sub-Saharan Africa (Nigeria)
      and Europe (Finland). The study consisted of 234 patients with breast carcinoma,
      admitted to the African Oncology Institute in Sabratha, Libya, during the years
      2002-2006. The pathological features were collected from pathology reports,
      patient histories from hospital files and the Sabratha Cancer Registry. The
      demographic differences between the Libyan, Nigerian and Finnish populations were
      prominent. The mean age of breast cancer patients in Libya was 46 years which was
      almost identical to that of Nigeria, but much lower than that of Finland. The
      Libyan breast cancer incidence was evaluated as 18.8 per 100,000 female
      individuals. This incidence was markedly higher in Finland, but was also high in
      Nigeria. Libyan and Nigerian breast cancer is predominantly of premenopausal type
      and exhibits unfavorable characteristics such as high histological grade and
      stage, large tumor size and frequent lymph node metastases. However, the
      histological types and histopathological risk features show similar importance
      regarding survival as European breast cancer cases. Survival in Libya ranks
      between the rates of survival in Nigeria (lowest) and Finland (highest). In
      conclusion, in Libya and other African countries, premenopausal breast cancer is
      more common than postmenopausal breast cancer. However, the opposite is true for
      Europe. Population differences may be involved, as suggested by the known
      variation, in the distribution of genetic markers in these populations. Different
      types of environmental impacts, however, cannot be excluded.

PMID- 22866086
TI  - Copy number increase of HER-2 in colorectal cancers.
AB  - HER-2 is involved in genetic instability and is overexpressed in a number of
      human carcinomas, including colorectal cancer (CRC). The choromosomal locus of
      HER-2, 17q21, is frequently amplified in breast cancer, but the correlation
      between copy-number variations and HER-2 overexpression in CRC has yet to be
      elucidated. The functional impact of such regions requires extensive
      investigation in large numbers of CRC samples. Case-matched tissues of colorectal
      adenocarcinomas and adjacent normal epithelia (n=134) were included in this
      study. Quantitative PCR was performed to examine the copy number and mRNA
      expression of HER-2 in CRC. The results showed that copy number gains of HER-2
      were detected in a relatively high percentage of CRC samples (35.1%, 47 out of
      134). A positive correlation was noted between the copy number increase of HER-2
      and tumor progression. Furthermore, copy number gains of HER-2 showed a positive
      correlation with mRNA overexpression in CRC. However, the expression levels of
      HER-2 mRNA were also enhanced in the group of CRC samples with unaltered copy
      numbers. In conclusion, the findings suggest that a copy number increase of HER-2
      is a potential diagnostic indicator for CRC; whether alone or in combination with
      other markers.

PMID- 22866087
TI  - Construction of a fusion expression plasmid containing the G250 gene and human
      granulocyte-macrophage colony stimulating factor and its significance in renal
      cell carcinoma.
AB  - This study aimed to construct a eukaryotic expression plasmid containing the
      G250/MN/CA IX (G250) and human granulocyte-macrophage colony stimulating factor
      (hGM-CSF) genes, and to detect the expression of these proteins in vitro by
      recombinant plasmids in eukaryotic cells. pORF-hGM-CSF and pcDNA3.0-G250 were
      used as the template to amplify G250 and hGM-CSF by routine polymerase chain
      reaction (PCR). The two PCR products were cloned into the eukaryotic vector
      pVAX1, in order to construct a recombinant plasmid pVAX1-G250-hGM, and the
      plasmid was transfected into human embryonic kidney 293 cells. The protein
      expression was then determined by immunocytochemistry, atomic force microscopy,
      ELISA and Western blotting. DNA sequencing showed that the cloned G250 and hGM
      CSF sequences were consistent with the reported Gene Bank ones. Moreover, a high
      expression was noted following recombinant plasmid transfection of the G250 and
      hGM-CSF proteins. Thus, the eukaryotic expression vector pVAX1-G250-hGM
      containing G250 and hGM-CSF was constructed, allowing for the investigation of
      the anti-G250 antigen vaccine and immune response mechanisms of biological
      immunotherapy in renal cell carcinoma.

PMID- 22866088
TI  - Gene expression of growth signaling pathways is up-regulated in CD133-positive
      medulloblastoma cells.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor in children. Cancer
      initiating cells (CICs) have been proposed to be involved in the development of
      brain tumors including MB. Prominin-1 antigen (CD133) is a candidate surface
      molecular marker for CICs. In the present study, CD133-positive cells were
      isolated from human Daoy MB cells and their gene expression was compared with
      that of control Daoy cells. DNA microarray analysis revealed that there were 398
      up-regulated genes (>2-fold increase) and 318 down-regulated genes (<50%
      decrease) in the CD133-positive cell-enriched fractions. Up-regulated genes
      included neuregulin-1, cyclin D1, cyclin-dependent kinase 6, vascular endothelial
      growth factor, inhibin beta A, promyelocytic leukemia gene, MYC, and hairy
      enhancer of split-1, which are components of growth signaling pathways. Molecular
      studies suggest that developmentally regulated signals important for stem cell
      maintenance are also involved in MB tumorigenesis. Moreover, these molecules can
      serve as novel targets for MB treatment.

PMID- 22866089
TI  - TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern
      and distribution.
AB  - Breast cancer remains a worldwide public health concern. The incidence and
      mortality of breast cancer varies significantly in ethnically and geographically
      distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has
      shown an increase in incidence and is characterized by early onset and
      aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that
      plays a significant role in breast carcinogenesis. Furthermore, studies have
      shown a correlation between certain p53 mutations and response to therapy in
      breast cancer. In the present study, TP53 mutations were identified by direct
      sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence
      of TP53 mutations in Arab breast cancer patients living in the KSA is among the
      highest in the world (40%). Notably, 73% of the patients whose tumors harbored
      p53 mutations were less than 50 years of age. Furthermore, for the first time, we
      identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably,
      all the novel point mutations were found in exon 4, wherein 29% of the mutations
      were localized. Furthermore, an excess of G:C->A:T transitions (49%) at non-CpG
      sites was noted, suggesting exposure to particular environmental carcinogens such
      as N-nitroso compounds. The results indicate that the TP53 gene plays a
      significant role in breast carcinogenesis and the early onset of the disease
      among Arab female individuals.

PMID- 22866090
TI  - Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and
      gastric cancer: a case-control study.
AB  - The transforming growth factor-beta (TGFbeta) pathway plays an important role in
      various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 
      875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate
      the associations between these polymorphisms and gastric cancer susceptibility,
      clinicopathological parameters and survival. A case-control study was conducted
      in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were
      determined by PCR-restriction fragment length polymorphism and DNA sequencing.
      Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly
      associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87;
      p=0.001) and certain subtypes of gastric cancer including intestinal type (OR,
      0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54
      0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008).
      Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a
      significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91;
      P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was
      associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI,
      0.32-0.57, p<0.001). No significant correlation was observed between
      polymorphisms and survival of gastric cancer patients. Our results suggest that
      both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased
      gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of
      gastric cancer according to clinicopathological parameters. A combination of the
      TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric
      cancer risk. These findings provide clues to the biological mechanisms that
      underline tumor heterogeneity.

PMID- 22866091
TI  - MDR-1 gene polymorphisms G2677T and C3435T in a case of Hodgkin's variant of
      Richter's syndrome.
AB  - Richter's syndrome is defined as the transformation of low-grade lymphoma to a
      more aggressive high-grade malignant form, usually diffuse large B-cell lymphoma.
      Hodgkin's lymphoma variant of Richter transformation is relatively rare, and only
      approximately 100 cases have been reported in the literature. This study examined
      a case of a 53-year-old woman who developed Hodgkin's lymphoma almost 5 years
      after the diagnosis of chronic lymphocytic leukemia (CLL). The major points of
      interest regarding CLL with Hodgkin's transformation were also considered, such
      as the potential role of MDR-1 gene polymorphisms. The patient was evaluated for
      two MDR-1 gene polymorphisms, G2677T polymorphism in exon 21 and silent C3435T
      polymorphism in exon 26, to ascertain whether polymorphisms affect the risk of
      Hodgkin's lymphoma variant of Richter transformation and whether genomic
      polymorphisms provide prognostic information on the clinical progression of the
      disease. According to the data obtained, the analysis of polymorphisms in the
      MDR1 gene exons 21 and 26 revealed that the T2677T and T3435T alleles are not a
      predisposing factor to Richter transformation, while the presence of the wild
      type genotype may be associated with a more favorable response to therapy.

PMID- 22866092
TI  - EGFR mutation: Significance as a stratification factor in the era of molecular
      targeted therapy.
AB  - Somatic mutations of epidermal growth factor receptor (EGFR) are the strongest
      predictive markers for the response to EGFR-tyrosine kinase inhibitors (TKIs).
      Patients with EGFR mutations generally receive EGFR-TKI treatment, and their
      survival has been significantly improved compared with that before the
      development of EGFR-TKIs. This study aimed to clarify the impact of EGFR
      mutational status on the survival of patients with non-small cell lung cancer
      (NSCLC) receiving cytotoxic agents, but not EGFR-TKIs, as their first-line
      chemotherapy. In addition, we analyzed patients with EGFR mutations to determine
      whether the timing of EGFR-TKI administration affects overall survival (OS). A
      total of 83 NSCLC patients with stage IIIB/IV who received chemotherapy alone and
      whose EGFR mutational status was known were investigated. Univariate and
      multivariate analysis for OS was performed using parameters such as age, gender,
      performance status (PS), histology, disease stage, smoking status, EGFR
      mutational status and administration of a first-line regimen. Among the 52
      patients with EGFR mutations who received EGFR-TKIs, OS between those who
      received EGFR-TKIs as their first-line treatment and after chemotherapy were
      similar. Among the 83 patients who received cytotoxic agents as their first-line
      chemotherapy, the multivariate analysis showed OS to be significantly associated
      with PS (p<0.001), histology (p=0.039) and EGFR mutational status (p=0.040). OS
      was almost similar among the 52 patients with EGFR mutations who received EGFR
      TKIs in a first- and second-line setting (25.6 vs. 26.8 months, p=0.914). The
      EGFR mutational status had a significant impact on the survival of NSCLC
      patients, although these patients did not receive EGFR-TKIs as their first-line
      chemotherapy. In future randomized trials, even when EGFR-TKIs are not included
      in experimental regimens, patients may need to be stratified by EGFR mutational
      status in order that study results be evaluated appropriately.

PMID- 22866093
TI  - Genetic testing and first presymptomatic diagnosis in Moroccan families at high
      risk for breast/ovarian cancer.
AB  - Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and
      ovarian cancers and are responsible for a substantial proportion of familial
      breast and ovarian cancers. No female individuals from families from Morocco
      affected by breast cancer with mutations of these genes have previously been
      reported, and clinicians in Morocco are unaccustomed to dealing with healthy
      female individuals carrying mutations in the BRCA genes. This study aimed to
      report the initial experience of a group of Moroccan investigators carrying out
      predictive genetic testing to detect a known familial mutation in healthy
      Moroccan females with a high risk of developing breast cancer and to introduce
      supervision of these asymptomatic female carriers as a new approach in the
      prevention and early diagnosis of breast and ovarian cancers in Morocco.
      Presymptomatic diagnosis was carried out using DNA genetic testing in 5 healthy
      Moroccan female individuals from three families with an elevated risk of
      developing breast cancer. These are the first Moroccan families reported to be
      affected by breast cancers associated with BRCA mutations. Presymptomatic
      diagnosis was carried out for breast cancer in 5 female individuals from three
      Moroccan families with BRCA mutations. Two of the families are the first reported
      incidence of the founder mutation Ashkenazi BRCA1-185_186delAG in Moroccan
      patients. The third family carried the known BRCA2 mutation
      c.5073dupA/p.trp1692metfsX3. We tested the presence of these mutations in 5
      asymptomatic healthy females from the three families. Two sisters from family 1
      carried the BRCA1-185_186delAG mutation, whereas the third female individual from
      family 2 carried the c.5073dupA/p.trp1692metfsX3 mutation. However, one healthy
      female individual and her mother from family 3 did not carry the familial
      mutation of the BRCA1 gene. This study found BRCA mutations in three asymptomatic
      subjects, suggesting that this is the first step towards the development of
      persistent medical monitoring of females from families with a history of breast
      and ovarian cancers. Consequently, it is crucial for oncologists in Morocco to
      initiate the supervision of healthy female individuals with genetic defects which
      may lead to hereditary cancers.

PMID- 22866094
TI  - Astrocyte elevated gene-1 and breast cancer (Review).
AB  - Astrocyte elevated gene-1 (AEG-1), also known as MTDH and Lyric, is a novel gene
      that was first cloned by subtraction hybridization in 2002 and has recently been
      shown to play a role as a crucial oncogene that acts as a promoter of tumor
      malignancy. Overexpression and inhibition studies both in in vitro and in vivo
      models have partly shown the oncogenic roles of AEG-1 in a number of crucial
      aspects of tumor development and progression, including transformation, evasion
      of apoptosis, proliferation, cell survival, migration, invasion, metastasis,
      angiogenesis and chemoresistance through the activation of numerous signaling
      pathways, such as the nuclear factor kappaB, PI3K/AKT, Wnt/beta-catenin and
      mitogen-activated protein kinase signaling pathways. However the potential roles
      of AEG-1, particularly in specific organs or tissues, such as breast tissue,
      require further clarification. Studies have found that in normal human breast
      tissue, AEG-1 is always expressed at low levels or is absent, while it is widely
      overexpressed in many breast cancer cell lines and breast tumors. The present
      review evaluates the current literature with regards to AEG-1 relative to breast
      cancer development and progression and highlights new perspectives relative to
      this molecule, indicating its potential to become a new target for the clinical
      treatment of breast cancer.

PMID- 22866095
TI  - Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a
      natural inhibitor of NF-kappaB.
AB  - Nuclear factor (NF)-kappaB has been shown to be associated with cancer resistance
      to radiotherapy (RT), and is constitutively active in the murine osteosarcoma
      cell line, LM8. Parthenolide has been reported to show antitumor activity through
      inhibition of the NF-kappaB pathway. In this study, we investigated the radio
      sensitizing activity of parthenolide. We established Luc-LM8, a stable
      transfectant reporter construct of NF-kappaB transcriptional activity into LM8.
      Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were
      cultured with or without parthenolide treatment, irradiated, and subjected to
      cell viability and apoptosis assays. In vivo, to investigate whether parthenolide
      enhances radio-sensitivity of tumors, a tumor growth assay was conducted.
      Parthenolide enhanced the growth inhibitory effect of RT and induced the
      apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was
      significantly suppressed in the mice treated with parthenolide and RT. The
      present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation.
      Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing
      drug for use in cancer RT.

PMID- 22866096
TI  - Expression of the serine protease inhibitor serpinA3 in human colorectal
      adenocarcinomas.
AB  - Proteases facilitate a number of steps in cancer progression. The serine protease
      inhibitors (serpins) are a protein superfamily with inhibitory activity against
      proteases. One of these proteases, serpinA3, appears to have a multifaceted role
      and is associated with inflammatory reactions, Alzheimer's disease, malignant
      melanoma and gastric cancer. To gain insight into the potential effect of
      serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in
      colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we
      noted a significantly lower serpinA3 level in cancer tissue compared to paired
      normal tissue. Moreover, the tumour serpinA3 level tended to be higher in
      disseminated disease as compared to localised disease. No significant difference
      in the plasma levels of serpinA3 was noted in the patients when compared to the
      controls. However, plasma serpinA3 and C-reactive protein (marker of
      inflammation) in the CRC patients and controls were significantly positively
      correlated. To confirm and detect localization of serpinA3 expression,
      immunohistochemistry was performed. Immunohistochemistry showed heterogeneous
      immunoreactivity in epithelial cells in the cancer and normal tissue and
      extracellular staining within bands of stroma as well as in some stromal cells. A
      Taq Man system was used to investigate a single nucleotide polymorphism (rs4934)
      in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion
      and expression. No significant difference was observed between CRC and control
      subjects regarding genotype and allelic distributions, nor were associations
      noted between clinical characteristics and serpinA3 levels. In conclusion, an
      altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC
      progression. SerpinA3 concentrations in plasma appear to be correlated with
      systemic inflammation, but do not appear to be specific to CRC patients. Further
      studies are warranted to improve our understanding of the role of serpinA3 in
      CRC.

PMID- 22866097
TI  - Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid
      tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation.
AB  - Lifeguard (LFG), an anti-apoptotic protein with high expression rates in breast
      cancer cells, has been identified as a molecule that inhibits death mediated by
      Fas. The molecular function of LFG and its regulation in the carcinogenesis of
      human breast and sarcoma cells, however, remains to be elucidated. In the present
      study, we investigated the ability of LFG expression to inhibit apoptosis induced
      by the alkyl-phospholipid perifosine. Results showed that LFG was able to be
      downregulated in selected sarcoma and breast cancer cell lines characterized by
      high endogenous LFG expression. A decreased LFG expression led to enhanced
      sensitivity to treatment with an agonistic Fas antibody or treatment with
      perifosine. Taken together, our findings indicate the role of LFG as an anti
      apoptotic protein and provide further evidence of the potential of LFG as a
      target for the development of novel therapeutic strategies.

PMID- 22866098
TI  - Fluorine-18-labeled boronophenylalanine positron emission tomography for oral
      cancers: Qualitative and quantitative analyses of malignant tumors and normal
      structures in oral and maxillofacial regions.
AB  - The present study aimed to demonstrate the features of fluorine-18-labeled
      boronophenylalanine positron emission tomography ((18)F-BPA-PET) to reveal oral
      cancer, as well as normal structures in the oral and maxillofacial regions. We
      analyzed (18)F-BPA-PET findings from 8 patients with histologically confirmed
      recurrent and/or advanced oral cancer scheduled for boron neutron capture
      therapy. The capacity of (18)F-BPA-PET to delineate tumor and normal structures
      was assessed qualitatively and quantitatively. Tumors were easily identified as
      high uptake areas in all cases. Although the eyes, which were depicted as a low
      uptake area, and tongue musculature were readily identified, major vessels were
      not noted in any of the cases. Areas corresponding to the surface of the dorsum
      tongue to middle pharynx were expressed as high uptake areas in all of the cases.
      Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8
      cases, while the dorsum tongue had the highest uptake area in the remaining 2
      cases. (18)F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it
      is crucial to note the presence of a high uptake area corresponding to the dorsum
      area of the tongue when diagnosing a tumor using this technique.

PMID- 22866099
TI  - Expression of CD44v6 is an independent prognostic factor for poor survival in
      patients with esophageal squamous cell carcinoma.
AB  - CD44v6 has been causally associated with the development of metastases and with
      poor prognosis in various human malignancies. To elucidate the
      clinicopathological significance of CD44v6 expression in esophageal squamous cell
      carcinoma (ESCC), the present study aimed to investigate the expression of CD44v6
      using immunohistological techniques. Using specific antibodies against CD44v6 and
      CD44s, expression of the proteins was analyzed immunohistochemically in 63
      primary esophageal ESCCs, which were previously resected at the Nagoya City
      University Hospital without pre-operative induction therapy. Using light
      microscopy, the positive expression of CD44v6 was divided into a low- or high
      expression group. The expression of CD44v6 in ESCC was analyzed with respect to
      various clinicopathological characteristics. The frequency of CD44v6 expression
      was 90.5% (57/63). The CD44v6 high-expression group comprised 55.6% of the
      patients (n=35) and the low expression group included 44.4% of the patients
      (n=28). In this study, no significant difference was observed between any
      clinicopathological factor and the immunohistochemical expression of CD44v6. In
      patients with high levels of CD44v6 expression, survival was markedly worse
      (p=0.0327). Favorable outcomes were observed for the clinicopathological
      characteristics of 6 patients whose tissue immunohistochemical expression of
      CD44v6 was not detected. Moreover, multivariate analysis confirmed that
      expression of CD44v6 was an independent prognostic indicator (risk ratio =2.793;
      p=0.0301). Overexpression of CD44v6 is a useful prognostic indicator of ESCC.
      Therefore, CD44v6 should be investigated as a potential target for therapy.

PMID- 22866100
TI  - Pulmonary tumor thrombotic microangiopathy caused by lung adenocarcinoma: Case
      report with review of the literature.
AB  - Pulmonary tumor thrombotic microangiopathy (PTTM) is an uncommon cancer-related
      complication characterized by intimal proliferation in pulmonary small arteries
      and arterioles with or without tumor emboli. In the majority of cases, the
      causative lesion is gastric poorly differentiated adenocarcinoma. In the present
      study, an autopsy case of PTTM caused by lung adenocarcinoma is reported and the
      pathogenesis of this complication is discussed. Multiple nodular lesions in the
      bilateral lungs were found in a 62-year-old Japanese man. Transbronchial biopsy
      revealed non-small cell carcinoma. Chemotherapy was performed; however, the
      patient succumbed to sudden dyspnea. Autopsy revealed poorly differentiated
      adenocarcinoma with multiple intrapulmonary metastases and intimal proliferation
      of pulmonary small arteries and arterioles with or without tumor emboli, which
      were characteristic of PTTM. Tumor cells were immunohistochemically positive for
      vascular endothelial growth factor (VEGF) and osteopontin (OPN), which are
      endothelial proliferative factors. This case indicates the possible involvement
      of VEGF and OPN in the pathogenesis of PTTM caused by lung adenocarcinoma.

PMID- 22866101
TI  - Patient satisfaction in treatment for cervical pathology.
AB  - This study aimed to analyse the satisfaction levels of patients treated for
      cervical dysplasia. At the Orbis Medical Center, all cases of abnormal cervical
      cytology are referred for colposcopy; however, there are three possible routings
      for patients: i) Patients are informed by the gynecologist about the colposcopy
      in a visit to the outpatient clinic, and colposcopy is planned in a second visit;
      ii) patients are informed by the gynecologist immediately before the colposcopy
      (a single visit); or iii) patients are called by a nurse practitioner 1-2 weeks
      prior to the colposcopy. The nurse practitioner informs patients about their Pap
      smear result, the colposcopy procedure and the follow-up (single visit plus
      telephone conversation). Patient satisfaction was analysed in the diagnostic and
      occasionally in the therapeutic colposcopies, with regards to information,
      treatment, appeasement and number of visits. The issue of whether the
      introduction of nurse practitioners improved patient satisfaction was also
      assessed. Patient satisfaction questionnaires were sent to all 593 patients who
      underwent a colposcopic examination for the first time following an abnormal
      smear test result. Data were analysed using SPSS 14.0. For statistical analyses,
      chi(2) tests and the Mann-Whitney U test were used. P<0.05 was considered to be
      statistically significant. The response rates did not differ significantly among
      the three groups of patients. In general, patient satisfaction regarding care was
      high (96%). The role of the nurse practitioner was rated highly (8.0-8.4).
      Although there were differences in the number of visits and satisfaction
      regarding the information provided, patient satisfaction did not differ
      significantly between groups 1 and 3. Patients in group 2 were significantly less
      satisfied with regard to almost all analysed data. In conclusion, the single
      visit procedure is extremely efficient. Patient satisfaction did not differ
      significantly between groups 1 and 3, but group 2 patients were significantly
      less satisfied. The introduction of nurse practitioners improves patients'
      knowledge, comfort and satisfaction. Furthermore, it reduces the number of visits
      required. Efficient treatment strategies were introduced and patient satisfaction
      was increased.

PMID- 22866102
TI  - Estradiol-mediated tumor neo-vascularization.
AB  - Neo-vascularization is essential for tumor growth and metastasis and is
      presumably initiated by bone marrow-derived endothelial progenitor cells (BM
      EPCs). These cells predominantly reside in the bone marrow and are recruited at
      sites of inflammation, tissue damage and tumors. The tissue-specific factors
      responsible for recruitment of BM-EPCs and neo-vascularization are the subject of
      intense investigation. Using bone marrow cells from Tek/green fluorescent protein
      (GFP) transgenic mice, we analyzed the effect of estrogen on the mobilization of
      BM-EPCs to orthotopically implanted cancer cells in estrogen- and non-estrogen
      supplemented ovariectomized mice. The donor marrow cells were unique as they were
      fluorescently tagged, allowing for the tracking of their migration to the tumor
      tissues. Results showed that GFP + BM-EPCs were incorporated within the tumor
      vasculature in comparison to the sham injections. Notably, estrogen
      supplementation enhanced the mobilization of BM-EPCs to the tumor site. This
      elevation shows that estrogen may affect tumor neo-vascularization by inducing
      the mobilization of BM-EPCs. Understanding and characterizing the mechanism
      involved in the estrogen-induced mobilization of BM-EPCs may serve as a 'Trojan
      horse' in the delivery of bio-molecules that may disrupt tumor vasculogenesis and
      induce the targeted killing of tumor cells.

PMID- 22866103
TI  - Protein expression status of p53 and epidermal growth factor receptor in thymoma.
AB  - Evaluating the state of malignancy of thymoma is a challenge due to the
      discrepancies between pathological classifications and clinical stage criteria.
      Therefore, the identification of markers contributing to the assessment of the
      stage of malignancy of thymoma would be useful. This study aimed to evaluate the
      prevalence of p53 and epidermal growth factor receptor (EGFR) in thymoma,
      demonstrate the clinical significance and assess the potential of specific
      targeted therapy. A total of 16 thymic hyperplasia patients and 43 thymoma
      patients were included in the study. Samples were tested for the expression of
      p53 and EGFR using immunohistochemistry. In the multivariate analysis, the
      thymoma cases were followed up to analyze the relationship between survival rates
      and a number of potential factors, such as p53 and EGFR. There were 21 completely
      resected stage II cases which were evaluated for relapse-free time. The
      distribution of p53 with clinicopathological parameters was: type A/AB 57.1%,
      type B1 85.7%, type B2 85.7%, type B3 90.9% and type C 100%; and stage I 90.9%,
      stage II 90.9%, stage III 100% and stage IV 100%. The EGFR-positive rates were:
      type A/AB 42.9%, type B1 71.4%, type B2 57.1%, type B3 90.9% and type C 100%; and
      stage I 45.5%, stage II 76%, stage III 75% and stage IV 100%. EGFR expression
      correlated with tumor size, pathological classification and advanced clinical
      stage, whereas p53 correlated only with pathological classifications. Findings of
      our multivariate analysis showed that neither p53 nor EGFR are independent
      prognostic factors. Nevertheless, the fact that a statistical difference (p<0.05)
      was noted in relapse-free survival time between the EGFR-positive and EGFR
      negative groups (48.182+/-33.757 vs. 76.3+/-10.339 months) suggests that EGFR
      plays a key role in thymoma progression. No positive results were found between
      the p53 groups following a survey conducted to assess relapse time. Therefore,
      the application of EGFR-targeting agents is warranted in invasive thymoma,
      whereas the targeting of p53 has yet to be elucidated.

PMID- 22866104
TI  - A multi-institutional phase II study of combination chemotherapy with S-1 plus
      cisplatin in patients with advanced non-small cell lung cancer.
AB  - S-1 is an oral anticancer fluoropyrimidine agent designed to elevate anticancer
      activity with a decrease in gastrointestinal toxicity. We conducted a phase II
      study to evaluate the efficacy and safety of combination chemotherapy with S-1
      plus cisplatin in patients with advanced non-small cell lung cancer (NSCLC).
      Chemotherapy-naive patients were treated with S-1 administered orally at 40
      mg/m(2) twice a day for 21 consecutive days, and cisplatin (60 mg/m(2)) infused
      intravenously on day 8, repeated every 5 weeks. Of the 44 patients enrolled in
      the study, 40 were assessable for efficacy and safety. The median number of
      cycles administered was 3 (range 1-9 cycles). Among the 40 assessable patients, 7
      partial responses were observed, with an overall response rate (RR) of 17.5% [95%
      confidence interval (CI), 5.2-29.8]. Patients with squamous cell carcinoma showed
      a significantly higher RR (55.5%) than those with adenocarcinoma (9.1%) or other
      types of NSCLC (0%). The median progression-free survival was 4.3 months (95% CI,
      3.4-4.9), the median survival time was 17.9 months (95% CI, 15.0-20.8), and the 1
      and 2-year survival rates were 63.3 and 27.3%, respectively. Major grade 3-4
      hematologic toxicities were leukocytopenia (7.5%), neutropenia (5.0%), anemia
      (15.0%) and thrombocytopenia (2.5%). No grade 4 non-hematologic toxicity or
      treatment-related death occurred. These results suggest that combination
      chemotherapy with S-1 plus cisplatin is a promising therapeutic candidate for
      patients with advanced NSCLC, particularly squamous cell carcinoma.

PMID- 22866105
TI  - Radiosensitization of human breast cancer cells to ultraviolet light by 5
      fluorouracil.
AB  - Ultraviolet light B (UVB) phototherapy is widely used to treat dermatological
      diseases and therefore may be a potential optional strategy in the treatment of a
      skin lesion infiltrated by a malignant tumor. Currently, little is known
      regarding the effect of UVB phototherapy on human breast cancer cells. The
      present study aimed to investigate the effect of UVB phototherapy, as well as the
      potential effect of 5-fluorouracil (5-FU), the first-line anticancer drug for
      breast cancer, on radiosensitizing MCF-7 human breast cancer cells, in an attempt
      to develop new therapeutic strategies for the treatment of locoregional
      recurrence of breast cancer. MCF-7 cells were incubated in the presence of 5-FU
      for 48 h, and UVB irradiation at 750 mJ/cm(2) was administered in the midterm of
      5-FU treatment. The viability of MCF-7 cells was analyzed by the trypan blue
      staining method. Apoptosis was quantified by flow cytometry and Hoechst 33258
      staining. The cell cycle was evaluated by flow cytometry after the staining of
      cells with propidium iodide. The combination treatment of 5-FU and UVB resulted
      in a strong potentiation of the inhibitory effect of MCF-7 cell growth, dependent
      on the intra-S phase cell cycle arrest and induction of apoptosis, when compared
      to treatment with 5-FU or UVB alone. In conclusion, 5-FU sensitized human breast
      cancer cells to UVB phototherapy, and this combination therapy is an effective
      and promising strategy for the treatment of breast cancer, particularly for
      locoregional recurrence.

PMID- 22866106
TI  - Comparison of protein profiles between acetonitrile- and non-acetonitrile-treated
      sera from patients with nasopharyngeal carcinomas.
AB  - Serum proteins may be abnormally increased or decreased during the occurrence and
      development of nasopharyngeal carcinoma (NPC). However, currently there are no
      simple or effective methods to collect and differentiate these abnormally
      secreted proteins from abundant serum proteins. In this study, acetonitrile was
      used to remove the majority of high-abundance proteins from serum samples
      obtained from patients with NPC. The samples were subjected to surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry with a CM10 (weak
      cation exchange) ProteinChip, and the resulting protein profiles were compared
      with those of non-acetonitrile-treated serum samples. The results showed that the
      protein profiles differed between the acetonitrile- and non-acetonitrile-treated
      sera from patients with NPC. A large proportion of the non-acetonitrile-treated
      NPC serum protein peaks were <6000 kDa, while the detection rate of protein peaks
      >6000 kDa was relatively higher in the acetonitrile-treated NPC sera, accounting
      for more than half of all protein peaks (26.2+37.5%). Few differentially
      upregulated proteins were lost, and the peak value density increased after
      acetonitrile treatment. In conclusion, acetonitrile treatment of serum samples is
      effective in removing high-abundance macromolecular proteins. Therefore,
      acetonitrile treatment can be applied for the investigation of serum proteomics
      and may aid in the identification of differentially expressed proteins.

PMID- 22866107
TI  - Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal
      cancer cells and mediates cellular migration.
AB  - Matrix metalloproteinases (MMPs) are associated with cancer cell invasion and
      metastasis, and are currently the most prominent proteases associated with
      tumorigenesis. In particular, abundant expression of MMP-13 in colorectal cancer
      (CRC) is correlated with poor survival and the existence of distant metastasis.
      As suggested by recent in vitro studies, MMP-13 expression is regulated in a toll
      like receptor (TLR)-9-dependent manner. In this study, we quantified the
      expression of MMP-13, TLR-9 and second messengers of the TLR signal transduction
      in CRC cells compared to colonic fibroblasts by RT-PCR. Furthermore, the effects
      of a selective TLR-9 stimulation on the expression of MMP-13 in CRC cells and
      colonic fibroblasts were analyzed. MMP-13 and TLR-9 as well as associated second
      messengers were simultaneously up-regulated in LS174 and SW620 cells compared to
      fibroblasts. Selective TLR-9 agonism with CpG oligonucleotides led to a
      significant increase in MMP-13 gene expression after 12 h of incubation in LS174
      cells and after 12 and 24 h in SW620 cells, but not when using GpC
      oligonucleotides as a control substance. By contrast, MMP-13 gene expression
      remained unchanged in colonic fibroblasts following treatment with CpG or GpC
      oligonucleotides. The effects of selective MMP-13 inhibition on cellular
      migration were analyzed in Boyden chamber experiments. In the presence of 10 and
      20 MUM of the specific MMP-13 inhibitor, CL-82198, migration of the LS174 cells
      was significantly reduced by 55 and 52%, respectively, compared to untreated
      cells. In conclusion, the results of this study provide evidence of the TLR-9
      dependent regulation of MMP-13 in CRC cells, but not in colonic fibroblasts.
      Since the specific inhibition of MMP-13 significantly reduces the migration of
      LS174 cells, selective MMP-13 inhibition may be a promising therapeutic strategy
      in CRC.

PMID- 22866108
TI  - Extranodal marginal zone B-cell lymphoma involving superior rectus muscle: A
      clinicopathological case report.
AB  - A 66-year-old female had suffered from proptosis in the left eye (OS) and double
      vision for 1 month due to abnormality of the superior rectus muscle. Visual
      acuity was noted as 20/20 in both eyes (OU). Eye movement showed limited OS
      supraduction. Magnetic resonance imaging revealed an indistinct mass in the orbit
      involving the superior rectus muscle. A biopsy specimen of the orbital tumor led
      to the histological diagnosis of extranodal marginal zone B-cell lymphoma.
      Radiotherapy with a total dosage of 30 Gy was administered, which subsequently
      resolved the tumor. However, the supraduction limitation of ocular movement
      remained unchanged. Supraduction limitation is due to muscular contraction
      disorder of the superior rectus muscle, caused by direct lymphoma cell invasion.

PMID- 22866109
TI  - Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following
      FOLFOX4 failure in elderly patients with metastatic colorectal cancer.
AB  - Previous studies have reported improved outcomes for elderly patients with
      metastatic colorectal cancer (mCRC) treated with oxaliplatin or irinotecan as
      first-line chemotherapy. However, few studies regarding second-line chemotherapy
      with oxaliplatin or irinotecan are currenlty available. We analyzed
      retrospectively the efficacy and toxicity in elderly patients (median age, 74
      years) treated with second-line FOLFIRI following first-line FOLFOX4 failure.
      From March 2005 to January 2008, 35 elderly patients with mCRC received first
      line FOLFOX4 comprising leucovorin, 5-FU and oxaliplatin followed by second-line
      FOLFIRI comprising leucovorin, 5-FU and irinotecan. The median number of
      treatment courses with FOLFIRI was 5 (range 2-32). One patient responded to the
      treatment. The disease control rate was 38.2%. The median time to treatment
      failure was 3 months, and the median overall survival (OS) time from the
      beginning of first-line chemotherapy was 20.7 months. The incidence of grade 3/4
      neutropenia was 71.4%, while febrile neutropenia was 11.4%. The incidence of non
      hematological toxicity was low. The use of the three active drugs, 5-FU,
      oxaliplatin and irinotecan, in mCRC produced the longest OS in elderly as well as
      in younger patients. However, the elderly patients treated with second-line
      FOLFIRI had a high rate of hematological toxicity. Second-line FOLFIRI may
      therefore be used with caution in the elderly.

PMID- 22866110
TI  - Prolonged survival in advanced thymoma: Effectiveness of sequential multiple
      lines of chemotherapy in an inoperable case.
AB  - A standard therapeutic approach for advanced malignant thymoma has yet to be
      defined given the rarity of this condition. We present a patient with advanced
      thymoma, evaluated as inoperable at diagnosis due to multiple serosal metastases.
      The strong constitution and determination of the patient allowed treatment with
      six distinct and subsequent chemotherapy regimens, all administered on an
      outpatient basis. A survival of 64 months from diagnosis was achieved. A
      favorable clinical response was obtained after the first three treatment lines,
      with the disappearance of all lesions on both computed tomography and positron
      emission tomography (PET) images. However, this result was not confirmed by
      surgical exploration of the thorax, undertaken with the aim of radical excision
      of possible residual disease. The presence of multiple pleural nodules, not
      evident on the imaging techniques, prevented even limited tumor debulking. The
      chemotherapy lines administered following detection of the lessions, stabilized
      the disease for a further 2 years, while a satisfactory quality of life was
      maintained. Only in the last months did the tumor progress and signs of
      cardiotoxicity appear, with the latter constituting the eventual cause of death.
      This case is important since the medical literature does not indicate non-cross
      resistant regimens for advanced thymoma following second-line chemotherapy, and
      the sequence of regimens presented in this case study may serve as a feasible
      outline program. Moreover, we highlight the known possibility of false-negative
      PET studies, which can occur despite the claimed glucose avidity of thymoma
      tissue.

PMID- 22866111
TI  - Tumors of the gastroesophageal junction have intermediate prognosis compared to
      tumors of the esophagus and stomach, but share the same clinical determinants.
AB  - The issue of whether carcinoma of the gastroesophageal junction (GEJ) should be
      considered a distal esophageal, a proximal gastric or an independent tumor, at
      least with regards to clinical evaluation and management remains controversial.
      This study included 613 retrospective consecutive patients with carcinoma of the
      upper digestive tract, 64 of the esophagus, 58 of the GEJ and 491 of the stomach.
      The prognostic impact of the main clinical and histological parameters was
      analyzed in relation to relative survival as an estimate of the excess mortality.
      Relative survival and standardized mortality ratio (SMR) were calculated from the
      observed survival and the expected survival of the general population with
      identical age, gender and calendar years of observation. Multivariate analyses
      were applied to the proportional hazards model of the relative survival. The
      excess mortality, expressed by the relative survival and SMR of the patients with
      GEJ carcinoma are intermediate compared to those of patients with esophageal and
      gastric tumors. However, prognosis is not determined by tumor location, histology
      or administration of adjuvant chemotherapy, but mainly by stage and radical
      surgical resection. Gender has a minor but significant prognostic effect and age
      showed a slight inverse correlation with excess mortality. In conclusion, the
      excess mortality related to the tumors of the upper digestive tract is determined
      by stage, radical resection, gender and age. The intermediate prognosis of GEJ
      tumors mainly depends on a particular combination of such elementary
      determinants.

PMID- 22866112
TI  - A review of the anti-tumor effect of the combined administration of a
      cyclooxygenase-2 selective inhibitor and a non-specific immunostimulant protein
      bound polysaccharide on an advanced colon cancer model using colon cancer cell
      lines.
AB  - The anti-tumor effect of a cyclooxygenase (COX)-2 selective inhibitor or a non
      specific immunostimulant (PSK) alone, as well as the anti-tumor effect of their
      combined administration were examined on a hepatic metastasis model of colon
      cancer using a colon 26 cell line (CT26) and its highly metastatic variant. Anti
      tumor effects were assessed by the number of hepatic metastases. Serum MMP-9, TGF
      beta and IL-6 were also measured. In a preliminary experiment, cells (5*10(5)) of
      a mouse colon cancer 26 cell line (CT26) and its highly metastatic variant were
      implanted below the splenic capsule in BALB/c and CDF1 mice. The number of
      hepatic metastatic CT26 cell lesions in the CDF1 mice of the non-spleen-removed
      group at 2 weeks was found to be optimum for the experiments. Although no
      significant difference was found, etodolac treatment showed the highest
      inhibitory effect on the number of hepatic metastases at a concentration of 30
      mg/kg. In contrast, intraperitoneal administration of 50 mg/kg PSK showed an
      inhibitory effect on hepatic metastases, but a significant difference was not
      observed. PSK (p=0.002) or the combined use of etodolac and PSK (p=0.001)
      exhibited a significant inhibition of the number of hepatic metastases. In
      addition, MMP-9 was significantly inhibited by the single use of etodolac or PSK,
      and was inhibited with an additive effect by the combined use of etodolac and
      PSK. IL-6 and TGF-beta were significantly inhibited following the combined use of
      etodolac and PSK. In conclusion, etodolac did not exhibit any significant hepatic
      metastasis inhibitory effect, whereas it significantly reduced the MMP-9 level.
      PSK reduced both the number of hepatic metastases and MMP-9. Combined use of
      etodolac and PSK did not show any additive effect in the inhibition of the number
      of hepatic metastases, whereas it inhibited MMP-9, TGF-beta and IL-6, suggesting
      the benefit of a combined effect.

PMID- 22866113
TI  - Kaposi's sarcoma developed after allogeneic hematopoietic stem cell
      transplantation.
AB  - A 33-year-old Chinese male patient with severe aplastic anemia received matched
      sibling allogeneic hematopoietic stem cell transplantation using antithymocyte
      globulin containing conditioning regimen after 4 months of unsuccessful treatment
      with cyclosporine A. Following transplantation, the patient was immunosuppressed
      demonstrated by intermittent infections, including a varicella 3 months after
      transplantation. Although DNA-STR results on day +30 confirmed complete donor
      engraftment, repeat DNA-STR analysis performed more than 3 months after
      transplantation showed a mosaic phenotype. Cyclosporine tapering commenced early,
      but the last DNA-STR result confirmed complete graft rejection. On day +198, the
      patient presented with fever, skin boil in the right temporal region, severe
      pancytopenia, intrabodominal lymphadenopathy and hepatosplenomegaly. Within 1
      month, superficial lymphadenopathy and right exophthalmos developed. Excisional
      lymph node biopsy pathology confirmed Kaposi's sarcoma (KS). The patient
      succumbed due to intracranial bleeding as a result of thrombocytopenia. This is
      the first study of KS that developed following stem cell transplantation for
      severe aplastic anemia. The precipitating factors underlying KS development in
      this case and its differentiation from post-transplant lymphoproliferative
      disorders are analyzed.

PMID- 22866114
TI  - Neurotransmitter gamma-aminobutyric acid-mediated inhibition of the invasive
      ability of cholangiocarcinoma cells.
AB  - The present study aimed to investigate the effect and mechanism of gamma
      aminobutyric acid (GABA) on the bio-nomics of cholangiocarcinoma QBC939 cells. A
      transwell cell culture chamber assay in vitro was used to detect the ability of
      invasion and metastasis of cholangiocarcinoma QBC939 cells. The expression of
      matrix metalloproteinase (MMP) mRNA and the enzymatic activity in QBC939 cells
      were detected by reverse transcription-polymerase chain reaction and gelatin
      zymography, respectively. Different concentrations of GABA inhibited the ability
      of the tumor cells in trans-Matrigel migration (100 MUmol/l GABA, 60+/-9.54 vs.
      42.67+/-4.04, P<0.05), and inhibited the activity and expression of MMP-2 and MMP
      9. GABA inhibited the invasion and metastasis of cholangiocarcinoma QBC939 cells,
      and the mechanism may involve the down-regulation of the activity of MMPs.

PMID- 22866115
TI  - Development and applications of a nasopharyngeal carcinoma Tet-Off cell line.
AB  - The conditional activation and inactivation of target gene expression in a
      nasopharyngeal carcinoma (NPC) cell line is beneficial for the study of the roles
      of NPC-related genes. Based on the Tet-Off Advanced system, a NPC S18 Tet-Off
      cell line was developed by stable transfection of a pTet-Off Advanced vector
      (regulator plasmid in Tet-Off Advanced system) into NPC S18 cells. Doxycycline
      dependent regulators expressed in the S18 Tet-Off cells were examined by
      transient and stable transfection of pTRE-Tight-Luc. The S18 Tet-Off-Luc clone
      selected by stable transfection of pTRE-Tight-Luc into S18 Tet-Off cells
      expressed firefly luciferase under tight control of doxycycline in a time- and
      dose-dependent manner. To test applications of the S18 Tet-Off cell line in the
      study of gene function, the impact of ferritin heavy chain (FTH1) gene on NPC
      cell growth was examined. The S18 Tet-Off-FTH1 clone was developed by stably
      transfecting pTRE-Tight-FTH1 (response plasmid harboring FTH1) into S18 Tet-Off
      cells. FTH1 levels in the S18 Tet-Off-FTH1 clone were semi-quantitatively
      regulated in response to varying concentrations of doxycycline. A cell
      proliferation assay showed that a high expression of FTH1 (cells grown in the
      absence of doxycycline) reduced cell growth, while moderate FTH1 overexpression
      (cells grown in 0.1 ng/ml doxycycline) had no adverse effect on cell growth. In
      conclusion, the S18 Tet-Off cell line provides a proven genetic background for
      convenient access to controllable gene expression in NPC.

PMID- 22866116
TI  - A clinical study of cytokine-induced killer cells for the treatment of refractory
      lymphoma.
AB  - Cytokine-induced killer (CIK) cell therapy, an adoptive T-cell immunotherapy, has
      been reported to be a safe and effective mode of treatment for patients with
      metastatic diseases, lymphoma and acute leukaemia. To investigate the clinical
      efficacy of cytokine-induced killer cells for the treatment of refractory
      lymphoma, the present clinical study was conducted. A total of 8 male patients
      with a mean age of 41 years (range 22-65) who were pathologically diagnosed with
      malignant lymphoma (Hodgkin's disease, 2 and non-Hodgkin's lymphoma, 6) were
      enrolled. CIK cells were expanded by priming with IFN-gamma, monoclonal antibody
      (mAb) to CD3 and IL-1alpha, followed by the addition of IL-2 the following day
      using peripheral blood mononuclear cells (PBMCs) of the 8 male patients. The CIK
      cells were then transfused back to the patients as treatment. On day 13, the CIK
      cell count reached 7-18*10(19) (mean, 12.7*10(9)), a 44- to 140-fold increase
      (mean, 98-fold). The average percentage of cells expressing CD3(+), CD4(+),
      CD8(+) and CD3(+)CD56(+) were also increased from 50.9+/-3.5, 29.9+/-1.7, 41.3+/
      3.2, 1.6+/-0.2% to 90.2+/-1.6, 40.6+/-5.5, 52.8+/-4.9 and 33.1+/-4.0%,
      respectively. Patients showed measurable radiographic tumor reduction, increased
      T-cell subset levels, and relief of symptoms after treatment. No severe toxicity
      or side effects were reported. CIK cells developed by this culture method have a
      high in vitro proliferation rate and tumor-killing capacity. In conclusion, CIK
      cell treatment of patients with malignant lymphoma achieves effective clinical
      responses, causing few side effects.

PMID- 22866117
TI  - Evaluation of intraoperative and postoperative complications related to
      lymphadenectomy in ovarian cancer patients.
AB  - Assessment of the regional lymph node status is an integral part of diagnostics
      for ovarian cancer patients. Due to the risk of complications, lymphadenectomy
      for ovarian cancer patients, as a routine treatment procedure, is still a subject
      of controversy. Therefore, the present study aimed to evaluate the frequency and
      nature of intraoperative and postoperative complications in ovarian cancer
      patients treated with surgery. In addition, a comparison of the frequency and
      nature of surgical complications between patients who underwent lymphadenectomy
      and those who did not was carried out. A retrospective analysis of 211
      consecutive ovarian cancer patients treated with surgery with pelvic and aortic
      lymphadenectomy (group I), and 258 ovarian cancer patients treated with surgery
      but without lymphadenectomy (group II) was carried out. All of the patients were
      treated with complementary chemotherapy. The frequency and nature of the
      intraoperative and postoperative complications were determined. The most frequent
      intraoperative complications in the two groups were haemorrhage, urinary system
      damage and digestive tract damage. The difference in the frequency and nature
      between the groups was not statistically significant (p=0.683). The most frequent
      postoperative complications were haemorrhage, intestinal junction dehiscence,
      eventrations, wound dehiscence, anaemia, wound healing complications and
      intestinal fistulas. Haemorrhage, eventrations and wound healing complications
      were more frequent in group I. The difference was statistically significant
      (p=0.002). Due to postoperative complications, reoperative procedures were
      necessary in two women in group II (0.78) and in 15 women (7.11%) in group I. The
      difference was statistically significant (p=0.000). In conclusion, the most
      frequent intraoperative complications were haemorrhage, urinary system damage and
      digestive tract damage. The frequency of complication was found to be similar in
      the two groups. A statistically significant higher rate of postoperative
      complications, such as haemorrhage, eventrations and wound healing complications
      was confirmed in the lymphadenectomy group.

PMID- 22866118
TI  - Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian
      cancer cell death.
AB  - Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the
      treatment of a variety of human diseases, including diabetes, obesity and cancer.
      Mounting evidence suggests that the inhibition of ACC induced of cancer cell
      apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3
      cancer cells has yet to be addressed. This study investigated the cytotoxic
      mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2
      furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian
      cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it
      induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was
      found to markedly enhance ACC phosphorylation, whereas AMP-activated protein
      kinase (AMPK) activator AICAR was found to marginally enhance ACC
      phosphorylation. Taken together, the data showed ACC is a potential novel
      molecular target of Taxol. Additionally, ACC inhibition partially contributed to
      the cytotoxic effect of Taxol in ovarian cancer cells.

PMID- 22866119
TI  - Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine
      in human chronic myeloid leukemia cells.
AB  - To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP)
      in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was
      established by stepwise selection of the CML cell line (K562). The results of the
      drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339
      fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells
      exhibited decreased accumulation and increased efflux of [(14)C]6-MP and its
      metabolites. In addition, K562-MP5 cells showed increased [(3)H]MTX transport.
      K562-MP5 cells over-expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA
      levels. Taken together, these results suggest that the up-regulation of P-gp,
      which contributes to the decreased accumulation by increasing the efflux of 6-MP
      and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.

PMID- 22866120
TI  - Induction of apoptosis in the SW620 colon carcinoma cell line by triterpene
      enriched extracts from Ganoderma lucidum through activation of caspase-3.
AB  - The medicinal mushroom Ganoderma lucidum (G. lucidum) has been used for the
      treatment of various diseases, and is known for the immune-enhancing activity of
      its polysaccharide. However, little is known about another of its major
      constituents, triterpene. This study investigated the anticancer mechanism of a
      triterpene-enriched extract from G. lucidum. The triterpene-enriched extract,
      GLAI, was prepared from fruiting bodies of G. lucidum by sequential hot water
      extraction, removal of ethanol-insoluble polysaccharides and gel-filtration
      chromatography. The mechanisms of GLAI-induced apoptosis on SW620 human
      colorectal adenocarcinoma cells were investigated. Tumor cell lines in vitro were
      treated with different concentrations of GLAI. Cell proliferation was measured by
      the Alamar blue assay, morphology of cell apoptosis was observed, cell apoptosis
      was detected by flow cytometry (FCM) and caspase-3 activity was detected by
      Caspase-3 cellular activity assay. The results showed that GLAI inhibited the
      growth of different tumor cells and caused significant apoptosis in a dose
      dependent manner. Marked morphological changes of cell apoptosis were observed
      after the cells had been exposed to GLAI for 24 h. The Caspase-3 assay results
      showed that the activity of the caspase-3 enzyme increased in both a time- and
      dose-dependent manner, whereas GLAI resulted in the down-regulation of Bcl-2 gene
      expression at the mRNA level and XIAP protein production at the protein level.
      Conversely, GLAI up-regulates the expression of the apoptosis enhancer Bax gene
      and p53 protein. These findings suggest that the triterpenes contained in G.
      lucidum are potential anticancer agents.

PMID- 22866121
TI  - Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and
      brown tumor of hyperparathyroidism.
AB  - A variety of diseases of the jaws may present multinucleated giant cells. These
      diseases include central giant cell lesions (CGCL), peripheral giant cell lesions
      (PGCL), brown tumor of hyperparathyroidism (BTH), and cherubism. The
      multinucleated giant cells in these lesions are osteoclast-like. Since NFATc1
      plays a significant role in osteoclast differentiation, the present study aimed
      to compare the expression of NFATc1 in CGCL, PGCL, BTH and cherubism. A total of
      14 formalin-fixed and paraffin-embedded tissue samples of CGCL (n=4), PGCL (n=5),
      BTH (n=3) and cherubism (n=2) were included in the study. An immunohistochemical
      analysis was performed to investigate the NFATc1 protein. The majority of giant
      cells in all of the cases were positive for nuclear NFATc1 and the immunostaining
      pattern was similar in all of the groups. Although our study supports the
      hypothesis that giant cell accumulation in PGCL, CGCL, BTH and cherubism is
      mediated by NFATc1, functional studies are required to investigate this
      hypothesis.

PMID- 22866122
TI  - Treatment strategies in intermediate cervical neoplasia: Implications of radical
      surgery.
AB  - Treatment strategies for cervical intraepithelial neoplase (CIN)2 lesions differ
      among gynaecologists. To evaluate the differences in management of treatment with
      subsequent implications, all surgical treatment strategies and follow-up methods
      were retrospectively analysed for patients with intermediate dysplasia of the
      cervix. This study aimed to evaluate expectant management strategies and the
      effect of biopsy prior to radical surgery in CIN2. Patients diagnosed with a CIN2
      lesion at the Orbis Medical Center in The Netherlands between 2006 and 2007 were
      retrospectively analysed. The follow-up ended on 1st January 2009. All 141
      patients with CIN2 lesions were included; 109 had no previous history of any CIN
      lesion. Of the 109 patients, 12% (n=13) underwent an immediate radical surgical
      excision of the transformation zone (LLETZ procedure) and 85% (n=93) underwent a
      local biopsy. After the lesion was biopsied, expectant management was selected
      for 59% of the patients. Subsequent smears were normal in 40% of the patients. Of
      the patients with abnormal smears in follow-up, the LLETZ procedure was performed
      in 86% of the patients (n=25). Of these cases, persistent disease was observed in
      14% of the patients. After an immediate LLETZ procedure without prior biopsy,
      follow-up smears were abnormal in 31% of the patients. Persistent disease was
      significantly lower following radical excision of the lesion with a diagnostic
      biopsy versus without one (14 versus 31%). After expectant management, the rate
      of persistent disease was 53% (p<0.001). Overall, the rate of persistent disease
      was 7%. Due to the high rate of persistent disease and the lower rate of
      overtreatment, CIN2 lesions should be treated by the excisional procedure. To
      restrict persistent disease, a biopsy is recommended prior to the actual
      treatment, since a higher rate of abnormal smears was observed in the follow-up
      after immediate radical excisions in the first visit.

PMID- 22866123
TI  - Deleted in liver cancer protein family in human malignancies (Review).
AB  - The Deleted in Liver Cancer (DLC) protein family comprises proteins that exert
      their function mainly by the Rho GTPase-activating protein (GAP) domain and by
      regulation of the small GTPases. Since Rho GTPases are key factors in cell
      proliferation, polarity, cytoskeletal remodeling and migration, the aberrant
      function of their regulators may lead to cell transformation. One subgroup of
      these proteins is the DLC family. It was found that the first identified gene
      from this family, DLC1, is often lost in hepatocellular carcinoma and may be
      involved as a tumor suppressor in the liver. Subsequent studies evaluated the
      hypothesis that the DLC1 gene acts as a tumor suppressor, not only in liver
      cancer, but also in other types of cancer. Following DLC1, two other members of
      the DLC protein family, DLC2 and DLC3, were identified. However, limited
      published data are available concerning the role of these proteins in malignant
      transformation. This review focuses on the structure and the role of DLC1 and its
      relatives in physiological conditions and summarizes data published thus far
      regarding DLC function in the neoplastic process.

PMID- 22866124
TI  - Revisiting cutaneous adverse reactions to pemetrexed.
AB  - Pemetrexed (Alimta(r)) is a multitargeted antifolate drug approved as a single
      agent or in combination with cisplatin for the treatment of a small number of
      malignancies including advanced and metastatic non-squamous non-small cell lung
      cancer (NSCLC), and malignant pleural mesothelioma. This review reports the
      recent peer-reviewed publications and original findings regarding cutaneous
      adverse reactions (CARs) to pemetrexed. Pemetrexed-related CARs are frequently
      reported under the unspecific term 'skin rash'. However, more specific diseases
      were tentatively identified as alopecias, urticarial vasculitis, acute
      generalized exanthematous pustulosis, toxic epidermal necrolysis, radiation
      recall dermatitis and pityriasis lichenoides. Most of the skin reactions occur
      shortly after pemetrexed administration. As with methotrexate-related CARs, the
      cell cycle arrest in the S phase may be regarded as a direct and major cause of
      the cytotoxic pathobiology. An adverse immune reaction is unlikely. In
      conclusion, pemetrexed is responsible for CARs exhibiting a variety of clinical
      presentations. Their origin is likely attributed to direct cytotoxicity following
      the cell cycle arrest in the S phase and cell necrosis.

PMID- 22866125
TI  - Synergistic antitumor efficacy by combining adriamycin with recombinant human
      endostatin in an osteosarcoma model.
AB  - In the last 15 years, chemotherapy-based therapeutic regimens for the treatment
      of osteosarcoma have failed to demonstrate improved survival rates. Novel
      approaches, including targeted therapy and antiangiogenic therapy, may provide
      new methods for the treatment of osteosarcoma, one of the most deadly malignant
      diseases. In the present study, the therapeutic efficacy of an endogenous
      angiogenesis inhibitor, endostatin, was tested in combination with the
      chemotherapeutic agent, adriamycin. BALB/c mice, aged 4-6 weeks were fed animal
      chow and had access to water ad libitum. The mice were divided into groups and
      injected with tumor cells. Immunohistochemical staining was performed to identify
      the microvessel density. The TUNEL technique was also used to determine the
      apoptotic index. The combination of endostatin and adriamycin produced marked
      synergistic antitumor activity in a mouse osteosarcoma model. These findings
      provide new guidelines for designing future clinical trials and for the
      application of currently available clinical drugs (endostatin has been approved
      for clinical use) in the treatment of osteosarcoma.

PMID- 22866126
TI  - Tissue factor pathway inhibitor-2 inhibits the growth and invasion of
      hepatocellular carcinoma cells and is inactivated in human hepatocellular
      carcinoma.
AB  - Human tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix
      associated Kunitz-type serine proteinase inhibitor that inhibits the plasmin- and
      trypsin-mediated activation of matrix metalloproteinases and inhibits tumor
      progression, invasion and metastasis. Previous studies have shown that TFPI-2 is
      downregulated in the progression of various tumors. The purpose of this study was
      to investigate the expression and function of TFPI-2 in hepatocellular carcinoma
      (HCC). In situ hybridization was used to detect human TFPI-2 mRNA and
      immunohistochemistry was performed to examine the role of TFPI-2 expression in
      hepatocarcinoma tissues. Cell proliferation was assessed using MTT assay. In situ
      hybridization and immunohistochemical analyses revealed that the expression of
      TFPI-2 in hepatocarcinoma tissues was markedly lower than that in tumor-adjacent
      normal hepatic tissues. Restored expression of TFPI-2 in HepG(2) cells inhibits
      cell proliferation and invasion. Taken together, the results suggest that TFPI-2
      has a tumor-suppression action and its inactivation may contribute to HCC.

PMID- 22866127
TI  - Endoscopic discrimination of sessile serrated adenomas from other serrated
      lesions.
AB  - Sessile serrated adenoma (SSA) is a proposed precursor of colorectal
      carcinogenesis. This study aimed to analyze the potential of endoscopy to
      discriminate SSA from other serrated lesions, specifically traditional serrated
      adenoma (TSA) and hyperplastic polyp (HP). Of 145 serrated lesions, 111 sessile
      serrated lesions including 32 TSAs, 25 SSAs and 54 HPs were analyzed for size,
      color, location and morphologic features using conventional endoscopy and
      magnifying chromoendoscopy. SSA was preferentially located in the right colon,
      whereas TSA and HP were located in the left colon. The sizes of SSA and TSA were
      larger than those of HP. The lesion color was indistinguishable among TSA, SSA
      and HP. Macroscopically, a pinecone-like or two-tier raised appearance were found
      more frequently in TSA than in SAA and HP. Under magnified chromoendoscopic
      observation, the stellar III(L) pit pattern and fern-like appearance were
      observed more frequently in TSA than in SAA and HP. In conclusion, endoscopic
      discrimination between SSA and other sessile serrated lesions based on
      morphological features was difficult. However, size and location of the lesions
      facilitated diagnosis.

PMID- 22866128
TI  - Protein-bound polysaccharide-K reduces colitic tumors and improves survival of
      inflammatory bowel disease in vivo.
AB  - Protein-bound polysaccharide-K (PSK) is a biological response modifier that
      possesses antitumor effects against various tumors. Although an inflammatory
      response has been considered to play an important role in the development of
      colorectal cancer, the anti-inflammatory effect of PSK has yet to be elucidated.
      An inflammatory bowel disease (IBD)-induced colorectal tumor model with 1.2
      dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS) was used to examine the
      effects of PSK on tumor suppression and survival. Although 90% of the mice that
      were not treated with PSK developed colitic tumors, oral administration of PSK
      suppressed tumor formation by less than 30%. Although deaths associated with DSS
      induced melena were observed, PSK significantly reduced mortality. In conclusion,
      the present study showed that PSK not only suppressed colorectal tumor formation
      in the DMH+DSS-induced IBD model, but also improved the survival rate, indicating
      that anti-inflammatory activity is one of the mechanisms for the antitumor
      effects of PSK.

PMID- 22866129
TI  - Extragastrointestinal stromal tumor originating from the vulva.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. They have gain-of-function mutations of the c-kit
      receptor tyrosine kinase gene and have been suggested to originate from the
      interstitial cells of Cajal. A small percentage of GISTs form
      extragastrointestinal masses. We report a rare case of a GIST originating from
      the vulva. A 55-year-old woman presented with a vulvar tumor. The tumor was
      initially diagnosed as a leiomyosarcoma following the first resection. Following
      a second recurrence the patient was administered chemotherapy. A third recurrence
      occurred and the patient underwent a third resection. Histology revealed that a
      bundle of fibrous tumor cells had invaded the connected tissue and muscular coat,
      and some spindle-shaped and blunt-ended nuclei were detected. Furthermore,
      immunohistochemical evaluation revealed that the tumor cells exhibited strong and
      diffuse staining for c-kit and CD34. The recurrent tumor was diagnosed as a GIST
      and a reevaluation of the original specimens also revealed a GIST. The patient
      was treated with imatinib, and is currently healthy with no evidence of
      recurrence at 20 months after the last surgery.

PMID- 22866130
TI  - Anal function-preserving subtotal intersphincteric resection/partial external
      sphincteric resection with hybrid 2-port hand-assisted laparoscopic surgery
      (Mukai's operation) for very low stage I rectal cancer: A case report.
AB  - A 62-year-old male patient underwent endoscopic mucosal resection (EMR).
      Additional hybrid 2-port hand-assisted laparoscopic surgery (HALS) (Mukai's
      operation) was performed for early rectal cancer located at the distal border of
      the rectum/below the peritoneal reflection (Rb) region [SM massive
      invasion/ly+/vertical margin (VM)X] via a small transverse incision,
      approximately 55 mm long, at the superior border of the pubic bone. After the
      pelvic floor muscles were dissected by laparoscopy-assisted manipulation,
      transanal subtotal intersphincteric resection (ISR) was performed under direct
      vision, securing a margin of more than 15 mm distal to the EMR scar. Partial
      external sphincteric resection (ESR) was also performed to obtain an adequate VM
      at the posterior region of the EMR scar. After bowel reconstruction, the layers
      were sutured transanally and a temporary covering colostomy was created. The
      resected specimen contained no residual tumor cells without lymph node
      metastasis. At 3 months after the operation, digital examination revealed good
      tonus of the anal muscles without stricture. The patient is currently undergoing
      rehabilitation of his anal sphincter muscles in preparation for the colostomy
      closure. In conclusion, subtotal ISR combined with partial ESR may decrease the
      need to perform Miles' operation for T1/2 stage I rectal cancer located at the
      distal border of the Rb region.

PMID- 22866131
TI  - A novel mutation in BRCA1 linked to breast and ovarian cancer and a genotype
      phenotype correlation.
AB  - We report a novel BRCA1 germline 4156delAA mutation detected in a 41-year-old
      woman with breast and ovarian cancer. Genomic DNA was obtained from peripheral
      blood. Standard polymerase chain reactions and direct sequencing were performed.
      This mutation originates a premature stop at codon 1354 of BRCA1 protein and has
      not been documented in any published report to the best of our knowledge. The
      mutation was not observed in any other family studied. Since this novel mutation
      was associated with both breast and ovarian cancer, the genotype-phenotype
      correlation was investigated in a patient base of 30 families.

PMID- 22866132
TI  - Clinical features of malignant melanoma of the finger and therapeutic efficacies
      of different treatments.
AB  - The purpose of this study was to explore the clinical features of malignant
      melanoma of the finger and therapeutic efficacies of different treatments. The
      clinical data of 22 patients with malignant melanoma of the finger (confirmed by
      pathological examination), admitted and treated in our hospital between February
      1995 and October 2007, were analyzed retrospectively. The primary site of the
      tumor was the thumb in 12 cases, index finger in 3 cases, middle finger in 3
      cases, ring finger in 2 cases and little finger in 2 cases. The most common
      presenting symptoms were pain and black patches on the fingers. A total of 15 of
      the 22 patients had subungual disease, 12 had a history of trauma and 2 had
      osteolytic bone lesions of the phalanx. The main treatments employed were
      surgery, chemotherapy and immunotherapy. Finger amputation was performed for all
      22 patients and axillary lymph node dissection in the same side was performed for
      13 patients. Nineteen cases were followed up for 1-10 years with an average of
      5.5 years. Three patients were lost to follow-up 2 years after treatment. The 1-,
      3- and 5-year survival rates were 86.4% (19/22), 42.1% (12/19) and 31.2% (6/19),
      respectively. In conclusion, malignant melanoma of the finger is a rarely
      occurring tumor. Comprehensive treatment, including surgery, chemotherapy and
      immunotherapy, is the key approach for malignant melanoma of the finger.
      Prognosis of the disease is associated with the size of the tumor, depth of
      infiltration and clinical stages.

PMID- 22866133
TI  - Synchronous primary carcinomas of the rectum and prostate: Report of three cases.
AB  - Multiple primary tumors (MPT) are a well-known phenomenon. Rapid advancements in
      diagnostics and therapeutics have contributed to a significant improvement in the
      survival rates of cancer patients, and also in an increase in the incidence of
      cases with multiple primary neoplasms, such as synchronous primary carcinomas of
      the rectum and prostate. We present a case history of a small number of male
      patients with synchronous primary carcinomas of the rectum and prostate. Two of
      the three cases were treated with lower anterior resection (LAR) and radical
      retropublic prostatectomy (RRP) during the same operation, and 1 case was treated
      with abdominoperineal resection (APR) and RRP during the same operation. No
      significant complications occurred during these operations. Our experience with
      these 3 cases of synchronous primary carcinomas of the rectum and prostate
      indicated that LAR or APR and RRP can safely be performed in a single operation.

PMID- 22866134
TI  - Basic fibroblast growth factor induces cholangiocarcinoma cell migration via
      activation of the MEK1/2 pathway.
AB  - The purpose of this study was to investigate the roles played by basic fibroblast
      growth factor (bFGF) in the induction of cholangiocarcinoma cell progression and
      to identify the signal transduction molecules that are activated by bFGF in
      cholangiocarcinoma cells. FGF receptor-2 (FGFR2) was shown to be expressed in two
      cholangiocarcinoma cell lines (RMCCA1 and KKU-100). Samples from RMCCA1 and KKU
      100 were assayed for the mRNA. Phosphorylation levels were determined by Western
      blotting. Treatment of the cholangiocarcinoma cells with bFGF enhanced signaling
      via the phosphorylation of MEK1/2, induced cholangiocarcinoma cell migration and
      resulted in high levels of actin polymerization. Moreover, treatment with a
      MEK1/2 inhibitor (U0126) attenuated the effect of bFGF-induced cholangiocarcinoma
      cell migration. Taken together, these observations indicate that bFGF enhances
      the migration of cholangiocarcinoma cells and that this enhancement is regulated
      by the phosphorylation of MEK1/2.

PMID- 22866135
TI  - Small-cell lung carcinoma with long-term survival: A case report.
AB  - Small-cell lung carcinoma is the most aggressive among lung cancer subtypes, has
      a poor prognosis and is highly associated with smoking. We present a case of
      small-cell lung carcinoma in a patient who had never smoked and has survived for
      14 years without achieving a complete remission since the first relapse. His long
      term survival may be ascribed to the slow growth of the cancer cells, limited
      metastasis and favorable responses to the treatments he has received. During
      these 14 years, only two lymph node metastases and a single metastasis to the
      brain developed. His small-cell lung carcinoma has been well controlled each time
      by the various treatments he has received, including chemotherapy, radiotherapy
      and surgery. Pathologically, the tumor was a typical small-cell lung carcinoma
      with extensive necrosis. Results showed the mitotic rate and the cell
      proliferation markers to be greater than those in the intermediate-grade atypical
      carcinoid, but relatively low. Thus, we conclude that this case belongs to an
      overlap between intermediate- and high-grade neuroendocrine tumors.

PMID- 22866136
TI  - Lysyl oxidase-like-1 enhances lung metastasis when lactate accumulation and
      monocarboxylate transporter expression are involved.
AB  - The role that lysyl oxidase-like-1 (LOXL-1) may play in cancer metastasis due to
      its specific collagen accumulation characteristics has not been investigated
      extensively. This study was performed to examine the role of LOXL-1 in cancer
      metastasis. In vitro and in vivo cancer metastasis experiments were performed
      with B16F10 cells. Using the immunoblotting technique, the expression of LOXL-1,
      monocarboxylate transporter (MCT)1/2 and matrix metalloproteinase (MMP)2/9 was
      examined in a cell culture model and in primary and metastatic site samples from
      non-small cell lung carcinoma patients. Immunohistochemistry was also performed.
      According to immunohistochemical analysis of the non-small cell lung carcinoma
      patient samples, LOXL-1, MCT1/2 and MMP2/9 were expressed more highly in
      metastatic sites compared to primary sites. In in vivo studies, LOXL-1
      overexpressing B16F10 cells yielded higher numbers of cancer nodules following
      their injection into mouse tail veins. Transfection of LOXL-1 siRNA into the
      cells prior to injection blocked lung metastasis. In vitro, the overexpression of
      LOXL-1 increased cell mobility and invasiveness, with increased extracellular
      accumulation of lactate at a low pH. The lactate transporter, MCT1/2, was highly
      expressed in LOXL-1-overexpressing cells. LOXL-1 knockdown through siRNA
      inhibited cell motility and invasiveness, showing relatively lower lactate
      accumulation and expression of MCT1/2 than under control conditions. This study
      elucidates extracellular pH-associated matrix degradation as a potential
      mechanism for LOXL-1-induced cancer metastasis.

PMID- 22866137
TI  - Effects of a concurrent chemoradiotherapy with S-1 for locally advanced oral
      cancer.
AB  - A number of regimens composed of concurrent chemoradiotherapy (CCRT) have been
      attempted as radical or adjuvant therapies for locally advanced oral cancer. CCRT
      with S-1 is considered promising due to its efficacy and simplicity of
      application. Patients (n=16) with locally advanced squamous cell carcinoma of the
      oral cavity were enrolled. Chemotherapy consisted of oral administration of S-1
      (65 mg/m(2)) for 14 consecutive days followed by a 1-week rest. Radiation
      treatment at a dose of 30 Gy in 15 fractions was administered concomitantly with
      S-1. A course schedule of 3 weeks of treatment was applied twice. The overall
      response rate was 87.5%. Median progression-free survival and median overall
      survival were 6.3 and 42.5 months, respectively. Although no grade 4 adverse
      events were observed, grade 3 adverse events, such as anemia (12.5%), stomatitis
      (25%) and anorexia (18.8%) were present. Thus, CCRT with S-1 is an effective
      modality that can be safely conducted with minimal burden on patients.

PMID- 22866138
TI  - Increased telomerase activity and hTERT expression in human salivary gland
      carcinomas.
AB  - Approximately 85% of human malignant tumors express increased levels of
      telomerase. The marked association of telomerase activity with malignant tissue
      provides strong evidence that telomerase activity is a significant marker for the
      diagnosis of cancer. In this study, telomerase activity was examined in 12 benign
      salivary gland tumors (8 pleomorphic adenomas and 4 adenolymphomas), 24 malignant
      tumors (15 mucoepidermoid carcinomas, 6 adenoid cystic carcinomas and 3 acinic
      cell carcinomas) and 6 non-neoplastic salivary glands. The mRNA expression of the
      human telomerase reverse transcriptase (hTERT) and additional telomerase
      associated proteins (hTEP1, p23, Hsp90 and dyskerin) was also examined. Of the 24
      malignant tumors, 15 revealed strong telomerase activity. The non-neoplastic
      salivary glands appeared to have a negative telomerase expression. Furthermore,
      telomerase activity was significantly higher in high-grade mucoepidermoid
      carcinomas compared to low-grade ones (Student's t-test, p<0.05). A significant
      correlation was found between telomerase activity and mRNA expression of hTERT in
      15 cases, including non-neoplastic salivary glands and tumors (Spearman's rank
      correlation test, p<0.05). Furthermore, a significant correlation was found
      between telomerase activity and mRNA expression of EGFR (Spearman's rank
      correlation test, p<0.001). The results suggest that not only hTERT, but also
      EGFR play a significant role in the activation of telomerase. In conclusion, the
      results suggest that telomerase activity and hTERT/EGFR mRNA expression are
      useful markers for the detection of malignant cells in salivary gland carcinomas.
      Moreover, our results indicated that telomerase activity determines the degree of
      malignancy of mucoepidermoid carcinoma.

PMID- 22866139
TI  - Clinical characteristics of hepatocellular carcinoma in elderly patients.
AB  - The incidence of hepatocellular carcinoma (HCC) in elderly patients in Japan has
      been on the increase. The aim of the present study was to evaluate the impact of
      aging on the clinicopathological findings and the survival of HCC patients. A
      total of 624 patients with HCC were examined in this study. The patients were
      classified according to their age at the time of diagnosis: one group comprised
      younger patients (<75 years; n=544) and the second comprised elderly patients
      [(>=75 years; n=80, (12%)]. Results showed that there were significantly more
      female patients (younger:elderly, 22:36; p=0.005), normal livers
      (younger:elderly, 0.3:6%; p=0.0002), non-viral HCC (younger:elderly, 11:31%;
      p<0.001) and solitary tumors (younger:elderly, 53:76%; p=0.0008) in the elderly
      group. Five out of seven (71%) non-B non-C (NBNC) HCC patients who developed HCC
      in the normal liver were elderly patients. Survival between the younger and
      elderly HCC groups was not significantly different (younger:elderly, 4.38:3.45
      years; p=0.665). Additionally, elderly HCC patients had fewer tumors, more mild
      underlying liver damage, and more frequent NBNC HCC. Their prognosis was not
      necessarily poorer than that of the younger HCC patients. Additionally, it
      appears that elderly patients develop HCC even without fibrosis. Therefore, aging
      may be a factor affecting hepatocarcinogenesis.

PMID- 22866140
TI  - Definitive chemoradiotherapy of limited-disease small cell lung cancer:
      Retrospective analysis of new predictive factors affecting treatment results.
AB  - The aim of this study was to evaluate potential predictive factors in the
      treatment of limited-disease small cell lung cancer (LD-SCLC). A total of 33
      patients with LD-SCLC who underwent definitive chemoradiotherapy at our institute
      between April 1996 and May 2007 were enrolled in our retrospective study. The
      relationship between a range of potential predictive factors and the initial
      response, time to progression and pattern of failure was analyzed. The factors
      evaluated included the tumor markers Pro-gastrin-releasing peptide (Pro-GRP) and
      neuron-specific enolase; net tumor size (sum of each lesion mass on computed
      tomography at 1-cm intervals); total radiation dose; biological effective dose
      (BED); overall treatment time (OTT); time between the start of any type of
      treatment and the end of radiation therapy (SER). In addition, the novel factors
      of radiation dose-intensity (RDI = BED/OTT) and RDI/NTS (= RDI/net tumor size)
      were defined. Of the 33 patients evaluated in our study, 22 (67%) achieved a
      complete response (CR) and 27 (82%) experienced treatment failure or recurrence.
      High RDI/NTS values showed a significant correlation with CR (P=0.043). Prolonged
      OTT and lower values of RDI and RDI/NTS showed a significant correlation with
      recurrence within 12 months (P=0.022, 0.033 and 0.015, respectively). The lower
      values of RDI and RDI/NTS showed a significant correlation with distant
      metastasis as a first failure site (P=0.038 and 0.044, respectively). Patients
      with RDI/NTS >=0.08 had a more favorable prognosis (P=0.045). Thus, RDI and
      RDI/NTS may become beneficial predictive factors in the treatment of LD-SCLC.
      However, further studies are required to confirm our preliminary results.

PMID- 22866141
TI  - Soluble interleukin-6 receptor to interleukin-6 (sIL-6R/IL-6) ratio in serum as a
      predictor of high Gleason sum at radical prostatectomy.
AB  - Approximately 40% of males with low Gleason grade clinically localized prostate
      cancer (PCa) at biopsy were finally diagnosed with high Gleason grade PCa at
      radical prostatectomy (RP). Therefore, a more reliable assessment of the Gleason
      grade prior to RP is required. Readily available modalities such as circulating
      biomarkers may be useful for this purpose. The aim of this study was to evaluate
      the ability of preoperative interleukin 6 (IL-6) and its soluble receptor (sIL
      6R), as well as urokinase-type plasminogen activator (u-PA), its receptor (u-PAR)
      and the inhibitor (PAI-1) to predict Gleason score upgrading. A total of 51 PCa
      patients with biopsy Gleason score <=7 were studied. IL-6 and sIL-6R, uPA, uPAR
      and PAI-1 preoperative serum levels were determined. Differences in the median
      and mean values of the preoperative blood levels of all biomarkers between
      patients with and without Gleason score upgrading were tested. The prognostic
      performance of each biomarker was further assessed by means of receiver operating
      characteristic (ROC) curves. The results showed the sIL-6R and sIL-6R/IL-6 ratio
      median levels to be significantly higher in patients who had Gleason score
      upgrading from <=7 at biopsy to >7 at RP (p=0.024 and p=0.011, respectively). The
      ROC curve revealed that sIL-6R and the sIL-6R/IL-6 ratio identified subjects at a
      high risk of upgrading [area under curve (AUC)=0.80 and AUC=0.83, respectively]
      with similar sensitivity and higher specificity for the ratio. The findings
      suggest that preoperative sIL-6R and sIL-6R/IL-6 ratio determination in serum are
      useful as prognostic biomarkers in PCa patients.

PMID- 22866142
TI  - Evaluation of biodistribution and antitumor effects of (188)Re-rhk5 in a mouse
      model of lung cancer.
AB  - Targeting drugs to receptors involved in tumor angiogenesis is considered to be a
      novel and promising approach to improve cancer treatment. This study aimed to
      evaluate the anti-tumor efficacy of (188)Re-labeled recombinant human plasminogen
      kringle 5 ((188)Re-rhk5) through [18F]-fluorodeoxyglucose (FDG) micro-positron
      emission tomography (PET). Radiolabeled rhk5 was obtained by conjugating the
      hystidine (6 x His) group at the carbon end of rhk5 with fac
      [(188)Re(H(2)O)(3)(CO)(3)](+). The biodistribution study of (188)Re-rhk5 showed
      that (188)Re-rhk5 had a high initial tumor uptake and prolonged tumor retention.
      The highest tumor uptake of (188)Re-rhk5 (3.65+/-0.82% ID/g) was found 2 h after
      injection which decreased to 0.81+/-0.14% ID/g 12 h after injection. Following
      therapy, tumor size measurement indicated that (188)Re-rhk5-treated tumors were
      smaller than (188)Re-, rhk5- and saline-treated controls 6 days after the
      treatment. In vivo 18F-FDG micro-PET imaging showed significantly reduced tumor
      metabolism in the (188)Re-rhk5-treated mice vs. those treated with rhk5, (188)Re
      and saline control, 1 day after treatment. Moreover, the number of microvessels
      was significantly reduced after (188)Re-rhk5 treatment as determined by CD31
      staining. Our results demonstrate that specific delivery of (188)Re-rhk5 allows
      preferential cytotoxicity to A549 lung cancer cells and tumor vasculature. (18)F
      FDG micro-PET is a non-invasive imaging tool that can be utilized to assess early
      tumor responses to (188)Re-rhk5 therapy.

PMID- 22866143
TI  - Differential expression of haptoglobin isoforms in chronic active hepatitis,
      cirrhosis and HCC related to HBV infection.
AB  - The three main complications of hepatitis B virus (HBV) infection are chronic
      active hepatitis (CAH), liver cirrhosis, and hepatocellular carcinoma (HCC). The
      aim of this study was to identify differentially expressed serum proteins among
      the three liver complications in patients with HBV infection. Differentially
      expressed proteins have been shown to be potential biomarkers for disease
      diagnosis, prognosis and therapy guidance. Two-dimensional polyacrylamid gel
      electrophoresis (2DE) combined with liquid chromatography tandem mass
      spectrometry (LC-MS/MS) was performed on sera from CAH, cirrhosis and HCC
      patients with HBV infection, as well as those obtained from healthy individuals.
      Of 54 differentially expressed (>=1.5-fold and p<0.05) protein spots, 35 spots
      were identified by LC-MS/MS. The identified spots correlated to 13 proteins. The
      proteins included haptoglobolin alpha-2 and beta isoforms, haptoglobin cleaved
      beta isoforms, retinol-binding protein, transthyretin, ficolin, leucine-rich
      alpha-2-glycoprotein, alpha-1-antitrypsin and clusterin. Of particular interest
      is the significant increase of haptoglobin alpha-2 isoforms in HCC patients
      compared to cirrhosis ones. In contrast, a significant decrease of the isoforms
      was noted among cirrhosis patients.

PMID- 22866144
TI  - Endostatin enhances radioresponse in breast cancer cells via alteration of
      substance P levels.
AB  - Radiotherapy is widely used in the treatment of cancer. On the other hand,
      endostatin is considered to be a potent inhibitor of angiogenesis. Therefore, to
      test whether ES combined with RT overcomes the limitations of each monotherapy
      the present study investigated the effects of endostatin (ES), radiotherapy (RT)
      or combination therapy on the growth of mouse breast cancer cells as well as on
      the expression of substance P in vitro. The breast cancer cell lines 4T1 and
      4THMpc were treated with recombinant murine ES (0.5, 1, 2, 4 and 8 ug/ml) alone,
      RT (45 Gy) alone or as a combination therapy. Cell proliferation was evaluated
      using an MTS assay and the results were verified by the Live/Dead assay.
      Immunoprecipitation and Western blotting analysis were performed to determine
      whether the substance P levels of the two cell lines occurred due to substance P
      content. Results showed that ES alone resulted in a low but significant
      inhibition in the growth of 4T1 and 4THMpc cell lines (27.63 and 21.75%,
      respectively). RT alone inhibited the growth of 4T1 (30.81%) and 4THMpc (39.64%)
      cells. A combination of ES with RT enhanced growth inhibition in the cells (83%
      in 4T1 and 80% in 4THMpc). The amount of substance P, both in the conditioned
      media and the cell lysates, increased within 72 h after RT. This increase was
      inhibited when ES and RT were applied in combination. These data indicate that ES
      inhibits the in vitro growth of breast cancer cells and potentiates the anti
      tumor effects of RT at appropriate doses via alteration of the amount of
      substance P and thus an increase of radioresponse.

PMID- 22866145
TI  - Management of neuroendocrine carcinomas of the breast: A rare entity.
AB  - Neuroendocrine (NE) carcinoma of the breast is extremely rare and constitutes
      less than 0.1% of all breast tumors. Only a few studies are currently available
      in the literature and a standard approach to treating this tumor has yet to be
      established. The aim of this study was to apply pathological treatment modalities
      in clinical practice and to select the most appropriate treatment accordingly.
      Six female patients were diagnosed with primary NE carcinoma of the breast. The
      patients underwent modified radical mastectomy with axillary dissection.
      Pathological specimens were stained with hematoxylin and eosin and an
      immunohistochemical panel of antibodies [neuron-specific enolase (NSE),
      chromogranin, synoptophysin, estrogen and progesterone receptor, c-erbB2 and Ki
      67]. The results showed that tumor size ranged from 2 to 4.5 cm in diameter.
      Lymph node metastasis was detected in 4 (67%) patients. Estrogen and progesterone
      receptor expression was found in 5 (83%) patients. None of the patients expressed
      c-erbB2. Chromogranin was found to be positive in 5 (83%) patients. Synoptophysin
      expression was detected in 5 (83%) patients. NSE was stained in 4 (67%) patients.
      An intraductal component was found in 5 (83%) patients. Lymphovascular invasion
      was found in 5 (83%) patients. Adjuvant chemotherapy was administered to patients
      with a Ki-67 index of >=10%. Radiotherapy was administered to 4 (67%) patients,
      and 4 (67%) patients received hormonal therapy. The mean follow-up time was 31.1
      months (range 12-52). All 6 patients survived, although following chemotherapy
      and tamoxifen, the disease progressed in 1 patient who received second-line
      hormonal therapy. In conclusion, NE carcinoma of the breast is a distinct entity.
      Management of this rare tumor may include surgery and radiotherapy depending on
      the size of the tumor and lymph node status. However, the exact role of
      chemotherapy and hormonal therapy has yet to be established. Adjuvant
      chemotherapy is recommended for patients with a Ki-67 index of >=10%, and
      hormonal treatment appears to be feasible in patients who are positive for
      estrogen and/or progesterone receptor.

PMID- 22866146
TI  - Genistein inhibits placental choriocarcinoma cell line JAR invasion through
      ERbeta/MTA3/Snail/E-cadherin pathway.
AB  - Genistein, the most abundant phytoestrogen in soybeans, may bind to estrogen
      receptors and perform anticancer activities. Choriocarcinoma is a malignant,
      trophoblastic and aggressive cancer of the placenta. Few studies are currently
      available concerning the effects of genistein on choriocarcinoma. In the present
      study, we investigated the effect of genistein on the invasive potential of the
      choriocarcinoma cell line JAR and its underlying mechanism. Our data revealed
      that genistein inhibited JAR cell invasion in a dose-dependent manner by a
      matrigel invasion assay. Moreover, genistein was found to have decreased the
      metastasis-associated gene MTA3 mRNA level, increased the transcriptional
      suppressor Snail mRNA level and upregulated the protein expression of the cell
      cell adhesion molecule E-cadherin by real-time RT-PCR and Western blot analysis,
      respectively. ERbeta siRNA was used to knock down ERbeta expression in JAR cells.
      In the ERbeta-knockdown JAR cells, genistein failed to inhibit JAR cell invasion.
      The effects of genistein on MTA3, Snail and E-cadherin expression were also
      eradicated following ERbeta siRNA transfection. These results demonstrated that
      genistein triggered the MTA3/Snail/E-cadherin regulatory pathway by binding with
      ERbeta, thereby inhibiting JAR cell invasion. In conclusion, our findings have
      significant implications for the prevention and therapy of choriocarcinoma.

PMID- 22866147
TI  - Correlation between increased copy number of mitochondrial DNA and
      clinicopathological stage in colorectal cancer.
AB  - Change of mitochondrial DNA (mtDNA) copy numbers is considered to be an important
      hallmark of cancers. However, whether quantitative changes in mtDNA occur during
      the initiation and progression of colorectal cancer remains to be determined.
      Quantitative change in mtDNA was observed during the initiation and progression
      of colorectal cancer and possible correlations of the mtDNA copy number in
      colorectal cancer with the clinicopathological stage were investigated. Tumor
      tissues and the corresponding non-cancerous tissues were surgically resected from
      24 colon and 20 rectal patients between 2008 and 2009. beta-actin expression was
      quantified in all of the specimens, and the copy numbers were calculated. In
      colorectal cancer, the quantitative changes of mtDNA exhibited a significant
      increase. In 24 cases of colon cancer, the average relative mtDNA copy number
      ratios were 115.15+/-31.57 in cancer tissues and 54.09+/-13.22 in the
      corresponding non-cancerous tissues (p<0.01). Furthermore, in 20 cases of rectal
      cancer, the ratios were 145.6+/-43.83 in cancer tissues and 55.58+/-12.47 in the
      corresponding non-cancerous tissues (p<0.001). Following correlation with
      clinicopathological data, change of the mtDNA copy number in colorectal cancer
      exhibited a significant association with clinicopathological stage, but no
      association with gender. Moreover, this increase was particularly marked in
      stages I and II. Our results indicate that mtDNA copy number plays a significant
      role during the initiation and progression of colorectal cancer, particularly
      during early clinicopathological stages.

PMID- 22866148
TI  - Role of reactive oxygen species in the synergistic cytotoxicity of safingol-based
      combination regimens with conventional chemotherapeutics.
AB  - Exploiting the sensitivity of cancer cells to reactive oxygen species (ROS) has
      been suggested as a strategy for the selective elimination of cancer cells. In
      this study, the ROS-generating sphingolipid safingol was combined with various
      conventional chemotherapeutics, and the potential synergism of the safingol-based
      combination regimen was assessed using a panel of cancer cell lines. The IC(50)
      values of safingol using as a single agent were 1.4-6.3 uM, which are
      concentrations that are clinically achievable. While synergism was dependent on
      the drug molar ratios, a 4:1 molar ratio of safingol to conventional
      chemotherapeutics exhibited a moderate to strong synergism in MDA-MB-231, JIMT-1,
      SKOV-3, U937 and KB cells, with combination indices ranging from 0.07 to 0.77.
      Furthermore, the addition of safingol may reduce the concentrations of
      conventional chemotherapeutics required to achieve 90% cell-kill by 1 to >3 log
      folds. A significant reduction in the cytotoxicity of safingol-based drug
      combinations was observed in the presence of N-acetyl-L-cysteine, suggesting that
      ROS is an important factor in mediating the observed synergism. Taken together,
      our results suggest that the use of safingol-based drug combinations is promising
      as an effective strategy for cancer therapy and should be investigated.

PMID- 22866149
TI  - Role of ERCC5 polymorphism in risk of hepatocellular carcinoma.
AB  - Excision repair cross-complementing rodent repair deficiency, complementation
      group 5 (ERCC5, XPG) is a key molecule in DNA damage repair. We analyzed the
      contribution of ERCC5 rs751402 polymorphism in increased susceptibility to
      hepatocellular carcinoma (HCC). A total of 96 patients diagnosed with HCC and 336
      healthy controls provided blood samples for analysis of rs751402 genotypes.
      Demographic data and information on habitual use of tobacco and alcohol were
      collected. After adjusting for covariates, rs751402 homozygocity for allele C was
      found to confer a statistically significant protection [adjusted odds ratio
      (AOR)=0.56; 95% CI, 0.35-0.89; p=0.01] against HCC, whereas rs751402 T alleles
      were associated with increased risk (AOR=1.69; 95% CI, 0.74-3.87). Individuals
      with the inherited ERCC rs751402 CC genotype may experience significant
      protection against HCC, whereas individuals with T alleles appear to be exposed
      to higher risk.

PMID- 22866150
TI  - Carbon and iron ion radiation-induced cytotoxicity and transformation in vitro.
AB  - The present study was undertaken to characterize carbon and iron ion radiation
      induced adverse biological effects in terms of toxicity and transformation in
      vitro. HTori-3 human thyroid epithelial cells were irradiated with 0.3-GeV/n
      (13.6 KeV/um) carbon ions and 1-GeV/n (150 KeV/um) iron ions, both of which
      represent high-mass, high atomic number (Z) and high-energy particles known as
      HZE particles, as well as gamma-rays. The survival of the irradiated cells was
      determined by a clonogenic survival assay. The yield of colonies growing in soft
      agar was used as a surrogate endpoint biomarker for transformation in vitro. The
      results showed that HZE particles and gamma-ray radiations are effective in
      increasing the yield of anchorage-independent colonies. Based on the relative
      biological effectiveness (RBE) values in the clonogenic survival assays, 0.3
      GeV/n carbon ions and 1-GeV/n iron ions were 2.9 and 2.4 times, respectively, as
      effective as gamma-rays at killing the irradiated HTori-3 cells. At a dose of 200
      cGy, 0.3-GeV/n carbon ions and 1-GeV/n iron ions were found to be 3.5 and 7.3
      times, respectively, as effective as gamma-rays at inducing anchorage-independent
      growth. These results suggest that the carcinogenic potential of 0.3-GeV/n carbon
      ions, as represented by the ability to induce anchorage-independent growth, may
      be lower than that of 1-GeV/n iron ions.

PMID- 22866151
TI  - Prevalence of topoisomerase I genetic mutations and UGT1A1 polymorphisms
      associated with irinotecan in individuals of Asian descent.
AB  - Topoisomerase I (TOP-I) mutations have been shown to be correlated to irinotecan
      resistance in vitro. However, the prevalence of TOP-I germline mutations has yet
      to be systematically elucidated. On the other hand, polymorphisms of UGT1A1 have
      been shown to be associated with CPT-11 toxicity in clinical situations. The
      primary aim of this study was to investigate the prevalence of mutations in the
      TOP-I exons associated with CPT-11 resistance, including untreated cancer tissue.
      A secondary aim was to confirm the less frequent UGT1A1*28 and more frequent
      UGT1A1*6 in individuals of Asian descent compared to Caucasians and individuals
      of African descent. The prevalence of 5 reported TOP-I mutations in exons was
      investigated in volunteers (n=236) using DNA sequencing of the PCR products. The
      prevalence of TOP-I mutations in untreated lung cancer tissues (n=16) was also
      investigated. Additionally, 3 UGT1A1 polymorphisms, UGT1A1*6, *27 and *28, were
      investigated in volunteers (n=126). There were no mutations of TOP-I in any of
      the 236 subjects or in the untreated lung tissues. Among 128 subjects, the
      distribution of homozygous polymorphisms of UGT1A1 was: UGT1A1*28 in 3 (2.4%) and
      UGT1A1*6 in 4 (3.2%) subjects, and co-occurrence of heterozygous polymorphisms
      for both UGT1A1*6 and UGT1A1*28 in 4 (3.2%) subjects, and for UGT1A1*27 and
      UGT1A1*28 in 1 subject (0.8%). The Hardy-Weinberg deviation test showed there was
      no significant deviation from the equilibrium, and the association analysis
      indicated no significant linkage between UGT1A1*6 and UGT1A1*28. In conclusion,
      TOP-I genetic mutations correlated to CPT-11 resistance were not detected in any
      of the subjects and untreated lung cancer tissues. Less frequent UGT1A1*28 and
      more frequent UGT1A1*6 were confirmed in East Asian individuals compared to
      Caucasians and individuals of African descent. Linkage disequilibrium was not
      detected between UGT1A1*6 and UGT1A1*28.

PMID- 22866152
TI  - The optimal age for performing surgery on patients with MEN 2B syndrome.
AB  - Multiple endocrine neoplasia (MEN) syndromes are characterized by the association
      of various endocrine neoplasias. Prophylactic thyroidectomy is the treatment of
      choice for patients with RET gene mutations. The age at which patients undergo
      prophylactic thyroidectomy may vary depending on the position of the RET gene
      codon. In cases of MEN 2B, when the mutation is carried in codons 883, 918 or
      922, prophylactic thyroidectomy is performed prior to 6 months of age, due to the
      increased aggressiveness of these heterozygosities, which are capable of
      determining the onset of medullary cancer during the first months of life. We
      present two heterozygous twin patients with MEN 2B syndrome who were born 32
      weeks premature, and who underwent prophylactic thyroidectomy at 7 months of age.
      The patients were carriers of the mutation at codon 918. We suggested the early
      surgery at 7 months as, due to their prematurity, the patients were required to
      gain weight to improve their condition prior to surgery. The two patients had
      medullary thyroid carcinoma without lymph node involvement. In conclusion, for a
      truly prophylactic thyroidectomy, such patients should undergo surgery within the
      first month of life, particularly if these patients are carriers of the mutation
      in codons 883, 918 or 922.

PMID- 22866153
TI  - Metastatic meningioma: The role of whole-body diffusion-weighted imaging.
AB  - We report the case of a 74-year-old male patient with a completely resected
      anaplastic meningioma who developed multiple metastases two years later
      (subcutaneous tissue near the surgical area, cervical lymph nodes, lung, pleura
      and bones). The primary tumor and all of the metastases showed a significant
      restricted diffusion. Whole-body diffusion-weighted imaging (DWI) was performed
      for assessment of the metastases. This case demonstrated the usefulness of this
      technique in screening extracranial metastases in patients with malignant
      meningiomas.

PMID- 22866154
TI  - Survivin promoter -31G/C polymorphism in oral cancer cell lines.
AB  - Survivin (SVV) is a protein that belongs to the inhibitor of apoptosis proteins
      (IAP) family and is involved in the G2/M phase progression of the cell cycle as a
      spindle-associated molecule. The biological features of this protein are well
      documented and its activity appears to be involved in mitochondria-dependent and 
      independent antiapoptotic pathways. Overexpression of SVV at the transcriptional
      and translational level has been associated with cancer, a multifactorial
      disorder in which the occurrence of a -31G to C polymorphism in the promoter
      region may significantly contribute to the development of this pathology. To
      verify this hypothesis, the occurrence of a single nucleotide polymorphism (SNP)
      in cis-acting cell cycle-dependent elements (CDEs) and in cell cycle homology
      regions (CHRs) of the survivin TATA-less promoter was investigated. A total of 23
      oral squamous cell carcinoma (OSCC) cell lines and normal epithelium-derived
      normal human epidermal keratinocyte (NHEK) cell lines were analyzed by RFLP and
      direct DNA sequencing of their promoter region. Furthermore, survivin expression
      at the transcriptional and translational levels was evaluated in these cells by
      RT-PCR and Western blotting, respectively. The findings indicate that the
      presence of a G or C allele is not directly correlated to survivin expression, at
      the mRNA or at the protein level, at least in the OSCC lines analyzed in this
      study.

PMID- 22866155
TI  - Beginning of personalized medicine in Panama: Molecular and pathological
      characteristics of gastrointestinal stromal tumors from archival paraffin
      embedded tissue.
AB  - This is the first study from Central America to analyze genetic mutations and
      histopathological features associated with gastrointestinal stromal tumors
      (GIST). Mutations found in the tyrosine kinase membrane receptors c-kit and
      pdgfra are associated with clinical and pathological characteristics of GIST. New
      drugs that inhibit the expression of these oncogenes at the molecular level
      substantially improve the quality of life for patients with this tumor. It is
      therefore essential for patient care in Panama that genetic analysis of GIST
      tumors continues to develop from the pilot study presented herein into routine
      clinical use. This study evaluated 39 cases of GIST in Panama, using samples
      archived at the Instituto Oncologico Nacional from 1994 to 2004. DNA from
      paraffin-embedded tumor tissues was isolated and amplified for the exons of c-kit
      and pdgfra associated with a high frequency of mutations. Direct PCR sequencing
      of specific exons was performed, and those with different alleles were cloned and
      re-sequenced. Amino acid sequences were inferred from DNA and aligned to Genbank
      reference sequences to determine the position and type of mutation. The highest
      frequency of mutations was found in exon 11 of the c-kit gene (70%). Mutations
      found in this exon were heterogeneous, while only one type of mutation
      (p.A502_Y503dup) was observed in c-kit exon 9. Mutations in the pdgfra gene
      constituted several substitutions, with the deletion p.D842V being observed most
      frequently. The observed GIST-associated mutations were previously described.
      Four patients with mutations associated with familial GIST were also found. The
      majority (66%) of patients with mutations in exon 11 (residues 550-591) were
      considered to be at high risk and 75% of patients with mutations specifically
      within residues 556-560 (exon 11) were considered to have high-risk GIST. This is
      the first molecular study of GIST in Central America. It was performed to gain a
      better understanding of the cancer-associated mutations of KIT and platelet
      derived growth factor receptor alpha (PDGFRA) receptors. This may aid in the
      prediction of clinical evolution and guide the use of specific drug treatments in
      patients with GIST in Panama.

PMID- 22866156
TI  - Myelosuppression induced by concurrent chemoradiotherapy as a prognostic factor
      for patients with locally advanced non-small cell lung cancer.
AB  - The aim of the present study was to assess whether myelosuppression during
      concurrent chemoradiotherapy is a prognostic factor for patients with locally
      advanced non-small cell lung cancer (NSCLC). We retrospectively analyzed 86
      patients with NSCLC who received concurrent platinum-based chemoradiotherapy.
      Patients were classified into two groups (grades 0-2 and 3-4) according to the
      most severe neutropenia, anemia or thrombocytopenia observed during concurrent
      chemoradiotherapy, and survival time and progression-free survival (PFS) time
      were analyzed. Univariate analysis revealed that overall survival time was
      significantly longer in patients with grade 0-2 anemia than in those with grade 3
      4 anemia (p=0.02). Survival time did not differ significantly on the basis of the
      severity of neutropenia or thrombocytopenia. Although pre-treatment white blood
      cell count was a further prognostic factor in univariate analysis, multivariate
      analysis revealed that the only independent prognostic factor for overall
      survival time was anemia. Disease stage was an independent prognostic factor for
      PFS (p=0.04), whereas neutropenia, anemia and thrombocytopenia were not. In
      conclusion, the severity of anemia during concurrent chemoradiotherapy may be a
      useful prognostic factor in patients with locally advanced NSCLC.

PMID- 22866157
TI  - Synergistic antitumor effects of liposomal honokiol combined with cisplatin in
      colon cancer models.
AB  - Honokiol, a novel antitumor agent, may induce apoptosis and inhibit the growth of
      vascular endothelium in a number of tumor cell lines and xenograft models. It has
      been proposed that the antitumor effects of chemotherapy may be increased in
      combination with an antiangiogenesis agent as an anticancer strategy. In the
      present study, we examined the potential of honokiol to increase the antitumor
      effect of cisplatin (DDP) when the agent and drug were combined in murine CT26
      colon cancer models, and investigated the underlying mechanism. Liposomal
      honokiol (LH) was prepared, and female BALB/c mice were administered LH at
      various doses to determine the optimum doses for honokial. Evaluation of cell
      apoptosis was analyzed using flow cytometry. Honokiol was encapsulated with
      liposome to improve its water insolubility. In vitro, LH inhibited the
      proliferation of CT26 cells via apoptosis and significantly enhanced the DPP
      induced apoptosis of CT26 cells. In vivo, the systemic administration of LH plus
      DDP resulted in the inhibition of subcutaneous tumor growth beyond the effects
      observed with either LH or DDP alone. This growth reduction was associated with
      elevated levels of apoptosis (TUNEL staining) and reduced endothelial cell
      density (CD31 staining) compared with either treatment alone. Collectively, these
      findings indicate that LH may augment the induction of apoptosis in CT26 cells in
      vitro and in vivo, and this combined treatment has exhibited synergistic
      suppression in tumor progression according to the synergistic analysis. The
      present study may be significant to future exploration of the potential
      application of the combined approach in the treatment of colon cancer.

PMID- 22866158
TI  - Risk of second cancer after initial treatment of breast cancer: An Osaka Cancer
      Registry Database study.
AB  - In the present study, the association between the incidence of second cancer and
      initial treatment for primary breast cancer was investigated using the Osaka
      Cancer Registry in Japan. We selected 45,575 patients diagnosed with breast
      cancer between January 1975 and December 2003. Information on initial cancer
      treatment and second cancer was obtained from the Osaka Cancer Registry. Patients
      were classified according to initial treatment (chemo-, hormone, or radiotherapy,
      or no treatment). We calculated the incidence rate ratio of second cancers in
      patients classified by treatment for the first cancer. The effects of treatment
      adjusted for covariates on second cancers were examined using stratified analyses
      and a Cox proportional hazard model. The final number of 33,043 subjects had a
      mean duration of follow-up of 5.2+/-4.3 years, during which 1,857 second cancers
      were diagnosed. For hormone therapy, the incidence rate ratio (IRR) of all second
      cancers was 0.64 [95% confidence interval (CI), 0.58-0.70], and that of corpus
      uteri cancer was 3.04 (95% CI, 1.78-5.19). The multivariate analysis revealed
      that the IRR of corpus uteri cancer associated with hormone therapy was 2.53 (95%
      CI, 1.41-4.55). The incidence rate of all second cancers associated with initial
      treatment was lower than that associated with no treatment. Only second corpus
      uteri cancer may be related to hormone therapy.

PMID- 22866159
TI  - Alternative surgical strategies in patients with sporadic medullary thyroid
      carcinoma: Long-term follow-up.
AB  - The extent of surgical resection in patients with sporadic medullary thyroid
      carcinoma (SMTC) remains controversial. The aim of the present study was to
      discuss the prognosis of sporadic medullary thyroid carcinoma with different
      surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at
      diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0).
      Having given their informed consent, 12 patients underwent total thyroidectomy
      with bilateral central neck dissection (group A), 40 underwent subtotal
      thyroidectomy preserving contralateral thyroid tissue on the entrance point of
      the recurrent laryngeal nerve into the larynx with ipsilateral modified radical
      neck dissection (group B), and 18 patients underwent subtotal thyroidectomy
      preserving contralateral thyroid tissue on the entrance point of the recurrent
      laryngeal nerve into the larynx with bilateral modified radical neck dissection
      (group C). The diagnosis was confirmed by a pathology examination. The incidences
      of hypoparathyroidism and recurrent laryngeal nerve injury, the cancer recurrence
      rates and survival time were investigated post-operatively. Significant
      differences were found between groups A, B and C in the incidence of
      hypoparathyroidism (chi(2)=40.9, P<0.01), as well as that of recurrent laryngeal
      nerve injury (chi(2)=32.9, P<0.01). The cancer recurrence rates in groups A, B
      and C were 75.0% (9/12), 2.5% (1/40) and 44.4% (8/18) respectively, (chi(2)=31.1,
      P<0.01) and the cure rates were 25, 97.5 and 55.6% respectively (chi(2)=31.1,
      P<0.01). The mean survival times in groups A, B and C were 77.8, 106.1 and 111.0
      months respectively, but significant difference was noted (chi(2)=3.2, P>0.05).
      In conclusion, compared to total thyroidectomy with bilateral central neck
      dissection, subtotal thyroidectomy with ipsilateral/bilateral modified radical
      neck dissection showed a lower incidence of hypoparathyroidism, recurrent
      laryngeal nerve injury and lower rates of recurrence, along with a similar
      cumulative survival.

PMID- 22866160
TI  - DRO1 sensitizes colorectal cancer cells to receptor-mediated apoptosis.
AB  - The molecule DRO1 (down-regulated by oncogenes 1) is a potential tumor suppressor
      protein that is frequently down-regulated in primary colorectal cancers and
      colorectal cancer cell lines. Although the mechanism of DRO1 action has yet to be
      elucidated, previous data have suggested that DRO1 interferes with tumor growth
      by sensitizing cells to apoptosis. The effect of DRO1 expression on receptor-,
      mitochondrial- and endoplasmic reticulum-mediated apoptosis in colorectal cancer
      cell lines was analyzed in this study, following the generation of DLD1/DRO1 and
      HCT116/DRO1 cell lines. Cells were cultured, and then analyzed using flow
      cytometry. DRO1 was found to sensitize cells to receptor-mediated apoptosis by
      promoting the activation of components of the death-inducing signaling complex
      (DISC).

PMID- 22866161
TI  - RNA interference against SPARC promotes the growth of U-87MG human malignant
      glioma cells.
AB  - Malignant glioma is a highly invasive brain tumor resistant to conventional
      therapies. Secreted protein acidic and rich in cysteine (SPARC) has been shown to
      facilitate glioma invasion. However, the effects of SPARC on cell growth have yet
      to be adequately elucidated. In this study, we constructed a plasmid expressing
      shRNA against SPARC, evaluated the effect of SPARCshRNA on SPARC expression and
      then assessed its effect on cell growth in U-87MG cells. Using plasmid-delivered
      shRNA, we effectively suppressed SPARC expression in U-87MG cells. Cell growth
      curves and colony formation assay suggested that the introduction of SPARCshRNA
      resulted in an increase of cell growth and colony formation. We also showed that
      knockdown of SPARC expression was capable of promoting the cell cycle progression
      from the G1 to S phase. However, no difference was found in the level of
      apoptosis. A molecular analysis of signal mediators indicated that the inhibition
      of p-c-Raf (Ser259) and accumulation of p-GSK-3beta (Ser9) and p-AKT (Ser473) may
      be connected with the growth promotion by SPARC shRNA. Our study may provide an
      insight into the biological function of SPARC in glioma.

PMID- 22866162
TI  - Detection of lung cancer with blood microRNA-21 expression levels in Chinese
      population.
AB  - The analysis of molecular markers in the biological field has been proposed as a
      useful tool for cancer diagnosis. MicroRNAs (miRNAs) may regulate diverse
      biological processes and play a significant role in tumorigenesis. The potential
      use of blood-based miRNAs as a biomarker of cancer and as a target for
      therapeutics is promising. The purpose of this study was to determine whether
      aberrant miRNA expression can be used as a molecular marker in peripheral blood
      for the diagnosis of lung cancer. Quantitative reverse transcription-polymerase
      chain reaction (qRT-PCR) was performed to analyze the expression levels of mature
      microRNA-21 (miR-21). Blood samples from 20 lung cancer patients and 10 healthy
      individuals were collected. The data were compared for the diagnosis of lung
      cancer. The results demonstrated that miR-21 was present in the peripheral blood
      in a markedly stable form and could be detected by real-time PCR sensitively and
      specifically. A significant difference was observed between the lung cancer cases
      and controls regarding miR-21 levels in peripheral blood (1947.26+/-930.56 pg/ml
      vs. 943.42+/-314.12 pg/ml, P=0.005). Furthermore, the over-expression of miR-21
      showed a highly discriminative receiver operating characteristic (ROC) curve
      profile, clearly distinguishing cancer patients from cancer-free subjects with an
      area under the ROC curve (AUROC) of 0.912+/-0.045. The detection of miR-21
      expression yielded 78.80% sensitivity and 100.00% specificity in the diagnosis of
      lung cancer. These findings indicate that in peripheral blood miR-21 may serve as
      a potential molecular marker for lung cancer and provide a new approach in the
      diagnosis of lung cancer.

PMID- 22866163
TI  - Overexpression of Hedgehog signaling molecules and its involvement in triple
      negative breast cancer.
AB  - The purpose of this study was to investigate the activation of Hedgehog (Hh)
      signaling molecules and its involvement in triple-negative breast cancer (TNBC).
      A total of 123 cases of paraffin blocks, including 83 cases of primary breast
      carcinoma, 30 cases of mammary hyperplasia and 10 cases of normal breast tissue,
      were immunohistochemically analyzed for Sonic Hedgehog (SHH), Patched-1 (PTCH1),
      Smoothened (SMO) and glioma-associated oncogene homoglog 1 (GLI1) expression. The
      expression of SMO and GLI1 in TNBC was significantly increased in comparison to
      non-triple-negative breast cancer (nTNBC). GLI1 expression manifested an inverse
      association with the estrogen receptor. The levels of GLI1 expression were
      increased in lymph node-positive cases. The expression of SHH and SMO was
      increased in high histological grades. Furthermore, the expression of SMO and
      GLI1 was correlated with superior tumor stage. The expression of SHH, SMO and
      GLI1 was significantly increased in breast cancer and mammary hyperplasia. PTCH1
      expression was significantly decreased in breast cancer compared to mammary
      hyperplasia and normal breast tissue. For the first time, clinical evidence has
      been provided in support of significant roles of Hh signaling in TNBC. Hh
      signaling is involved in breast ductal changes and malignant transformation.
      Measures to inhibit Hh activity may improve the prognosis of TNBC patients.

PMID- 22866164
TI  - A genomic approach to investigate expression profiles in Slovenian patients with
      gastric cancer.
AB  - Despite its decreasing frequency in developed countries, gastric cancer remains a
      significant health burden. The aim of the present study was to construct cDNA
      libraries and analyze differentially expressed genes related to this disease.
      Gene expression profiles were generated with suppressive subtraction
      hybridization (SSH). We constructed eight SSH libraries, four representing up
      regulated genes and four representing down-regulated genes in tumor tissues. Our
      approach revealed that several genes are abnormally expressed in gastric cancer.
      We also identified global deregulation of several pathways involved in the
      maintenance of normal gastric homeostasis. The results of this study support the
      view that, as a result of complex pathogenesis, diversity of genomic aberrations
      and multiplicity of carcinogenic causes, gastric cancer cannot be reduced to a
      single molecule. Our results may contribute new insight into molecular aspects of
      the disease and may prove advantageous for future development of therapeutic
      targets and diagnostic molecular markers.

PMID- 22866165
TI  - Effect of tumour necrosis factor-alpha on estrogen metabolic pathways in breast
      cancer cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has
      been linked to breast cancer development. Estrogen metabolic pathway is also
      involved in breast carcinogenesis and DNA adducts formation. In this study we
      investigated the effect of TNF-alpha on the estrogen metabolic pathway in MCF-7,
      a breast cancer cell line. Capillary liquid chromatography/mass spectrometry
      (LC/MS) and High performance liquid chromatography (HPLC) were used for analysis
      of estrogen metabolites and estrogen-DNA adducts levels respectively. Reporter
      gene assay, Real time reverse transcription polymerase chain reaction (real time
      RT-PCR) and Western blot were used to assess the expression of estrogen
      metabolizing genes and enzymes. TNF-alpha significantly increased the total EM
      and decreased the estrone (E1) / 17-beta estradiol (E2) ratio. Moreover, it
      altered the expression of genes and enzymes involved in E2 activation and
      deactivation pathways e.g. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1
      (CYP1B1), Catechol-O-methyl transferase (COMT) and Nicotinamide adenine
      dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were
      increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2
      hydroxyestradiol (2-OHE2) with decreased levels of methylated catechols e.g. 2
      methoxy estradiol (2-MeOE2). DNA adducts especially 4-OHE1-[2]-1-N3 Adenine was
      significantly increased. TNF-alpha directs the estrogen metabolism into more
      hormonally active and carcinogenic products in MCF-7. This may implicate a new
      possible explanation for inflammation associated breast cancer.

PMID- 22866166
TI  - Primary Refractory and Relapsed Classical Hodgkin Lymphoma - Significance of
      Differential CD15 Expression in Hodgkin-Reed-Sternberg Cells.
AB  - We recognized a few possible complications of classical Hodgkin lymphoma therapy
      in a cohort of 209 patients: 8 developed a primary refractory disease (primary
      progression), 36 showed an early relapse and 21 showed a late relapse. Sialyl
      CD15 expression in Hodgkin-Reed-Sternberg cells was significantly more positive
      in primary refractory Hodgkin lymphoma, which confirms our previously published
      findings. Bcl-2 showed a significantly lower level of expression in primary
      refractory disease than in the other follow-up groups. This is in contrast with a
      previous finding of Bcl-2, associated with a poor prognosis in primary refractory
      illness. Another category of variables, old age and advanced stages, was
      significantly different in the various complications but this finding is probably
      to be expected. We could not demonstrate a difference between the sequels and the
      control group with regard to several clinical and immunohistochemical markers.
      Sialyl-CD15 and Bcl-2 expression, in contrast, were confirmed as prognostic
      factors, mainly of tumor progression into primary refractory disease.

PMID- 22866167
TI  - Infiltrating lobular carcinoma of the breast presenting as gastrointestinal
      obstruction: a mini review.
AB  - One in twelve American women will develop breast cancer, with infiltrating
      lobular carcinoma (ILC) comprising approximately 15% of these cases. The
      incidence of ILC has been increasing over the last several decades. It has been
      hypothesized that this increase is associated with combined replacement hormonal
      therapy. Although pathologically distinct from infiltrating ductal carcinoma
      (IDC), ILC is treated in the same manner as IDC. However, ILC demonstrates
      significantly different patterns of late local recurrence and distant metastasis.
      The incidence of extra-hepatic gastrointestinal metastases is reported to be 6%
      to 18%, with stomach being most common. Herein, we present a brief review of the
      literature and a typical case involving ILC initially presenting as a small bowel
      obstruction. Evidence suggests that the late clinical patterns of ILC are
      distinctly separate from IDC and physicians need be cognizant of its late local
      recurrence and unique late metastatic pattern. Different follow up strategy
      should be entertained in patients with ILC.

PMID- 22866168
TI  - Inhibition of Breast Tumor Cell Growth by Ectopic Expression of p16/INK4A Via
      Combined Effects of Cell Cycle Arrest, Senescence and Apoptotic Induction, and
      Angiogenesis Inhibition.
AB  - p16-mediated inhibition of cancer cell proliferation and tumor suppression have
      been studied before,; the common consensus is that p16's cell-cycle arrest
      function plays a primary role in these actions, with some additional apoptotic
      induction by p16. However, other effects of p16 that may potentially contribute
      to p16-mediated anti-tumor ability have not been well studied. The emerging data
      including ours indicated that p16 contributes its anti-cancer ability by inducing
      tumor cells to senescence. Moreover, we showed that p16 inhibits breast cancer
      cell growth by inhibiting the VEGF signaling pathway and angiogenesis. In this
      study, we used adenoviral-mediated p16 expression (AdRSVp16) and breast cancer
      cell line MDA-MB-231 as the model to simultaneously analyze all these p16's anti
      tumor functions. We demonstrated that adenoviral-mediated p16 expression
      exhibited multiple anti-tumor functions by simultaneously suppressing in vitro
      growth and in vivo angiogenesis of breast cancer cells, blocking cell division,
      as well as inducing senescence and apoptosis. The in vivo study implies that
      p16's effect on anti-angiogenesis may play a more significant role than its anti
      cell proliferation in the overall suppression of tumor growth. These results
      suggest, for the first time, that AdRSVp16-mediated tumor suppression results
      from a combination of p16's multiple anti-tumor functions including p16's well
      known anti-proliferation/cell division function, apoptotic and senescence
      induction function, and its lesser-known/under-investigated anti-angiogenesis
      function. These combined results strongly indicate that p16 gene therapy has a
      multi-module platform with different anti-tumor functions; therefore, this study
      justifies and promotes the viral-mediated p16 gene therapy as a promising and
      powerful treatment approach for cancer patients due to p16's multiple anti-tumor
      functions.

PMID- 22866169
TI  - Assessing Population Level Genetic Instability via Moving Average.
AB  - Tumoral tissues tend to generally exhibit aberrations in DNA copy number that are
      associated with the development and progression of cancer. Genotyping methods
      such as array-based comparative genomic hybridization (aCGH) provide means to
      identify copy number variation across the entire genome. To address some of the
      shortfalls of existing methods of DNA copy number data analysis, including strong
      model assumptions, lack of accounting for sampling variability of estimators, and
      the assumption that clones are independent, we propose a simple graphical
      approach to assess population-level genetic alterations over the entire genome
      based on moving average. Furthermore, existing methods primarily focus on
      segmentation and do not examine the association of covariates with genetic
      instability. In our methods, covariates are incorporated through a possibly mis
      specified working model and sampling variabilities of estimators are approximated
      using a resampling method that is based on perturbing observed processes. Our
      proposal, which is applicable to partial, entire or multiple chromosomes, is
      illustrated through application to aCGH studies of two brain tumor types,
      meningioma and glioma.

PMID- 22866170
TI  - Lessons learned when innovations go awry: a baseline description of a behavioral
      trial-the Enhancing Fitness in Older Overweight Veterans with Impaired Fasting
      Glucose study.
AB  - Individuals diagnosed with impaired glucose tolerance (i.e., prediabetes) are at
      increased risk for developing diabetes. We proposed a clinical trial with a novel
      adaptive randomization designed to examine the impact of a home-based physical
      activity (PA) counseling intervention on metabolic risk in prediabetic elders.
      This manuscript details the lessons learned relative to recruitment, study
      design, and implementation of a 12-month randomized controlled PA counseling
      trial. A detailed discussion on how we responded to unforeseen challenges is
      provided. A total of 302 older patients with prediabetes were randomly assigned
      to either PA counseling or usual care. A novel adaptive design that reallocated
      counseling intensity based on self-report of adherence to PA was initiated but
      revised when rates of non-response were lower than projected. This study presents
      baseline participant characteristics and discusses unwelcome adaptations to a
      highly innovative study design to increase PA and enhance glucose metabolism when
      the best-laid plans went awry.

PMID- 22866171
TI  - Psychometrics and Cross-Cultural Comparisons of the Illustration-Based Assessment
      of Liability and Exposure to Substance Use and Antisocial Behavior(c) for
      Children.
AB  - Elementary school-age child report instruments that do not require reading or
      interviews are lacking. In four samples, psychometric estimates for 5- to 9-year
      olds were obtained for the Assessment of Liability and Exposure to Substance use
      and Antisocial behavior(c) (ALEXSA(c)), a child-report instrument that can be
      completed even by illiterate children. Invariance between minority groups vs
      Caucasians also was tested. Samples were: high-risk, low SES African-Americans
      (n=337), youth of varied ethnicities experiencing chronic stress (n=209), Mexican
      migrants in a reading remediation program (n=45), and U.S. twins (42 pairs) who
      were nearly all Caucasian. Validity criteria consisted of child-, parent-,
      teacher- and research evaluator-ratings on previously developed research and
      clinical instruments. Replicating results with older samples, ALEXSA factors had
      adequate or better reliabilities and demonstrated validity in all four studies.
      Ethnic invariance was found except for differences that were expected due to
      migrant's after-school program. In sum, psychometrics of the ALEXSA were
      supported for 5- to 9-year-olds of varied races/ethnicities, risk levels and
      academic skills.

PMID- 22866172
TI  - Folding of Intrinsically Disordered Protein Phosphatase 1 Regulatory Proteins.
AB  - Intrinsically disordered but biologically active proteins, commonly referred to
      as IDPs, are readily identified in many biological systems and play critical
      roles in multiple protein regulatory processes. While disordered in their unbound
      states, IDPs often, but not always, fold upon binding with their protein
      interaction partners. Here, we discuss how a class of IDPs directs the targeting,
      specificity and activity of Protein Phosphatase 1 (PP1). PP1 is major ser/thr
      phosphatase that plays a critical role in a broad range of biological processes,
      from muscle contraction to memory formation. In the cell, PP1 is regulated
      through its interaction with more than 200 regulatory proteins, the majority of
      which are IDPs. Critically, these PP1:regulatory protein holoenzyme complexes
      confer specificity to PP1 and are thus the functional forms of the PP1 enzyme in
      vivo. Furthermore, we discuss the distinct modes of interaction utilized by IDPs
      to complex with their protein binding partners. We subsequently show, by
      integrating multiple biophysical tools, that the majority of IDPs that regulate
      PP1, prefer a conformational selection model.

PMID- 22866173
TI  - Stochastic model of in-vivo X4 emergence during HIV infection: implications for
      the CCR5 inhibitor maraviroc.
AB  - The emergence of X4 tropic viral strains throughout the course of HIV infection
      is associated with poorer prognostic outcomes and faster progressions to AIDS
      than for patients in whom R5 viral strains predominate. Here we investigate a
      stochastic model to account for the emergence of X4 virus via mutational
      intermediates of lower fitness that exhibit dual/mixed (D/M) tropism, and employ
      the model to investigate whether the administration of CCR5 blockers in-vivo is
      likely to promote a shift towards X4 tropism. We show that the proposed
      stochastic model can account for X4 emergence with a median time of approximately
      4 years post-infection as a result of: 1.) random stochastic mutations in the V3
      region of env during the reverse transcription step of infection; 2.) increasing
      numbers of CXCR4-expressing activated naive CD4+ T cells with declining total
      CD4+ T cell counts, thereby providing increased numbers of activated target cells
      for productive infection by X4 virus. Our model indicates that administration of
      the CCR5 blocker maraviroc does not promote a shift towards X4 tropism, assuming
      sufficient efficacy of background therapy (BT). However our modelling also
      indicates that administration of maraviroc as a monotherapy or with BT of
      suboptimal efficacy can promote emergence of X4 tropic virus, resulting in
      accelerated progression to AIDS. Taken together, our results demonstrate that
      maraviroc is safe and effective if co-administered with sufficiently potent BT,
      but that suboptimal BT may promote X4 emergence and accelerated progression to
      AIDS. These results underscore the clinical importance for careful selection of
      BT when CCR5 blockers are administered in-vivo.

PMID- 22866175
TI  - The repeated replacement method: a pure Lagrangian meshfree method for
      computational fluid dynamics.
AB  - In this paper we describe the repeated replacement method (RRM), a new meshfree
      method for computational fluid dynamics (CFD). RRM simulates fluid flow by
      modeling compressible fluids' tendency to evolve towards a state of constant
      density, velocity, and pressure. To evolve a fluid flow simulation forward in
      time, RRM repeatedly "chops out" fluid from active areas and replaces it with new
      "flattened" fluid cells with the same mass, momentum, and energy. We call the new
      cells "flattened" because we give them constant density, velocity, and pressure,
      even though the chopped-out fluid may have had gradients in these primitive
      variables. RRM adaptively chooses the sizes and locations of the areas it chops
      out and replaces. It creates more and smaller new cells in areas of high
      gradient, and fewer and larger new cells in areas of lower gradient. This
      naturally leads to an adaptive level of accuracy, where more computational effort
      is spent on active areas of the fluid, and less effort is spent on inactive
      areas. We show that for common test problems, RRM produces results similar to
      other high-resolution CFD methods, while using a very different mathematical
      framework. RRM does not use Riemann solvers, flux or slope limiters, a mesh, or a
      stencil, and it operates in a purely Lagrangian mode. RRM also does not evaluate
      numerical derivatives, does not integrate equations of motion, and does not solve
      systems of equations.

PMID- 22866174
TI  - Combination of sulindac and dichloroacetate kills cancer cells via oxidative
      damage.
AB  - Sulindac is an FDA-approved non-steroidal anti-inflammatory drug with documented
      anticancer activities. Our recent studies showed that sulindac selectively
      enhanced the killing of cancer cells exposed to oxidizing agents via production
      of reactive oxygen species (ROS) resulting in mitochondrial dysfunction. This
      effect of sulindac and oxidative stress on cancer cells could be related to the
      defect in respiration in cancer cells, first described by Warburg 50 years ago,
      known as the Warburg effect. We postulated that sulindac might enhance the
      selective killing of cancer cells when combined with any compound that alters
      mitochondrial respiration. To test this hypothesis we have used dichloroacetate
      (DCA), which is known to shift pyruvate metabolism away from lactic acid
      formation to respiration. One might expect that DCA, since it stimulates aerobic
      metabolism, could stress mitochondrial respiration in cancer cells, which would
      result in enhanced killing in the presence of sulindac. In this study, we have
      shown that the combination of sulindac and DCA enhances the selective killing of
      A549 and SCC25 cancer cells under the conditions used. As predicted, the
      mechanism of killing involves ROS production, mitochondrial dysfunction, JNK
      signaling and death by apoptosis. Our results suggest that the sulindac-DCA drug
      combination may provide an effective cancer therapy.

PMID- 22866176
TI  - Correlated dynamics in egocentric communication networks.
AB  - We investigate the communication sequences of millions of people through two
      different channels and analyse the fine grained temporal structure of correlated
      event trains induced by single individuals. By focusing on correlations between
      the heterogeneous dynamics and the topology of egocentric networks we find that
      the bursty trains usually evolve for pairs of individuals rather than for the ego
      and his/her several neighbours, thus burstiness is a property of the links rather
      than of the nodes. We compare the directional balance of calls and short messages
      within bursty trains to the average on the actual link and show that for the
      trains of voice calls the imbalance is significantly enhanced, while for short
      messages the balance within the trains increases. These effects can be partly
      traced back to the technological constraints (for short messages) and partly to
      the human behavioural features (voice calls). We define a model that is able to
      reproduce the empirical results and may help us to understand better the
      mechanisms driving technology mediated human communication dynamics.

PMID- 22866177
TI  - The other in me: interpersonal multisensory stimulation changes the mental
      representation of the self.
AB  - BACKGROUND: Recent studies have shown that the well-known effect of multisensory
      stimulation on body-awareness can be extended to self-recognition. Seeing someone
      else's face being touched at the same time as one's own face elicits changes in
      the mental representation of the self-face. We sought to further elucidate the
      underlying mechanisms and the effects of interpersonal multisensory stimulation
      (IMS) on the mental representation of the self and others. METHODOLOGY/PRINCIPAL
      FINDINGS: Participants saw an unfamiliar face being touched synchronously or
      asynchronously with their own face, as if they were looking in the mirror.
      Following synchronous, but not asynchronous, IMS, participants assimilated
      features of the other's face in the mental representation of their own face as
      evidenced by the change in the point of subjective equality for morphed pictures
      of the two faces. Interestingly, synchronous IMS resulted in a unidirectional
      change in the self-other distinction, affecting recognition of one's own face,
      but not recognition of the other's face. The participants' autonomic responses to
      objects approaching the other's face were higher following synchronous than
      asynchronous IMS, but this increase was not specific to the pattern of IMS in
      interaction with the viewed object. Finally, synchronous, as compared to
      asynchronous, IMS resulted in significant differences in participants' ratings of
      their experience, but unlike other bodily illusions, positive changes in
      subjective experience were related to the perceived physical similarity between
      the two faces, and not to identification. CONCLUSIONS/SIGNIFICANCE: Synchronous
      IMS produces quantifiable changes in the mental representations of one's face, as
      measured behaviorally. Changes in autonomic responses and in the subjective
      experience of self-identification were broadly consistent with patterns observed
      in other bodily illusions, but less robust. Overall, shared multisensory
      experiences between self and other can change the mental representation of one's
      identity, and the perceived similarity of others relative to one's self.

PMID- 22866178
TI  - Effect of vitamin D supplementation on Mycobacterium tuberculosis-induced innate
      immune responses in a Canadian Dene First Nations cohort.
AB  - Canadian First Nations (FN) population experiences a high burden of tuberculosis.
      Vitamin D is known to enhance the expression of innate immune effectors,
      including cathelicidin LL-37, for protection against infections. In this study we
      performed longitudinal analyses to investigate the impact of vitamin D
      supplementation on macrophage responses to Mycobacterium tuberculosis (Mtb)
      lipoprotein (TLR2/1L), in Canadian Dene FN participants compared to Caucasian
      participants. Serum 25(OH)D and LL-37 levels were evaluated by ELISA.
      Transcriptional responses and protein expression of TLR2/1L-induced LL-37 and
      other innate immune cytokines were monitored in monocyte-derived macrophages
      (MDMs) before and after 8 months of vitamin D supplementation. In this study we
      showed that serum levels of LL-37 decreased after vitamin D supplementation in
      both Dene and Caucasian participants. There was no difference in TLR2/1L-induced
      LL-37 expression in MDMs in the two groups, either pre- or post-vitamin D
      supplementation. However, vitamin D supplementation markedly enhanced TLR2/1L
      induced responses in MDMs e.g. IL-6, IL-12 and IL-23 among Caucasians but not in
      the Dene participants. In contrast, after vitamin D supplementation TLR2/1L
      induced responses e.g. IL-1beta, IL-8 and IL-12 were significantly reduced in the
      Dene MDMs. These results indicate that vitamin D supplementation enhanced TLR2/1L
      induced innate immune macrophage responses in the Caucasian but not in the Dene
      participants. We hypothesize that cytokines may be differentially regulated in
      Canadian FN compared to Caucasians, in particular those that influence Th-1 and
      Th-17 responses required for the control of Mtb.

PMID- 22866179
TI  - Integrated metabolo-proteomic approach to decipher the mechanisms by which wheat
      QTL (Fhb1) contributes to resistance against Fusarium graminearum.
AB  - BACKGROUND: Resistance in plants to pathogen attack can be qualitative or
      quantitative. For the latter, hundreds of quantitative trait loci (QTLs) have
      been identified, but the mechanisms of resistance are largely unknown. Integrated
      non-target metabolomics and proteomics, using high resolution hybrid mass
      spectrometry, were applied to identify the mechanisms of resistance governed by
      the fusarium head blight resistance locus, Fhb1, in the near isogenic lines
      derived from wheat genotype Nyubai. FINDINGS: The metabolomic and proteomic
      profiles were compared between the near isogenic lines (NIL) with resistant and
      susceptible alleles of Fhb1 upon F. graminearum or mock-inoculation. The
      resistance-related metabolites and proteins identified were mapped to metabolic
      pathways. Metabolites of the shunt phenylpropanoid pathway such as
      hydroxycinnamic acid amides, phenolic glucosides and flavonoids were induced only
      in the resistant NIL, or induced at higher abundances in resistant than in
      susceptible NIL, following pathogen inoculation. The identities of these
      metabolites were confirmed, with fragmentation patterns, using the high
      resolution LC-LTQ-Orbitrap. Concurrently, the enzymes of phenylpropanoid
      biosynthesis such as cinnamyl alcohol dehydrogenase, caffeoyl-CoA O
      methyltransferase, caffeic acid O-methyltransferase, flavonoid O
      methyltransferase, agmatine coumaroyltransferase and peroxidase were also up
      regulated. Increased cell wall thickening due to deposition of hydroxycinnamic
      acid amides and flavonoids was confirmed by histo-chemical localization of the
      metabolites using confocal microscopy. CONCLUSION: The present study demonstrates
      that the resistance in Fhb1 derived from the wheat genotype Nyubai is mainly
      associated with cell wall thickening due to deposition of hydroxycinnamic acid
      amides, phenolic glucosides and flavonoids, but not with the conversion of
      deoxynivalenol to less toxic deoxynivalenol 3-O-glucoside.

PMID- 22866180
TI  - Photophysical properties of blue - emitting silicon nanoparticles.
AB  - Silicon nanoparticles with strong blue photoluminescence were synthesized by
      electrochemical etching of silicon wafers and ultrasonically removed under N(2)
      atmosphere in organic solvents to produce colloids. Thermal treatment leads to
      the formation of colloidal Si particles of 3 +/- 1 nm diameter, which upon
      excitation with 340 - 380 nm light exhibited room temperature luminescence in the
      range from 400 to 500 nm. The emission and the one- and two-photon excitation
      spectra of the particles are not sensitive to surface functionalization with
      methyl 2-methylprop-2-enoate. However, the derivatized particles show higher
      emission quantum yields in air-saturated suspensions (44%) than the underivatized
      particles (27%), as well as higher stability of its dispersions.FTIR and XPS
      spectra indicate a significant surface oxidation of the particles. The Si:O:C
      ratio at the surface of the derivatized particles estimated from XPS is
      Si(3)O(6)(C(5)O(2)H(y))(1), with y = 7 - 8. Vibronic spacing is observed in both
      the emission and excitation spectra. The information obtained from one-photon
      excitation experiments (emission and excitation spectra, photoluminescence
      quantum yields, luminescence decay lifetimes and anisotropy correlation
      lifetimes), as well as from two-photon excitation fluorescence correlation
      spectroscopy (brightness and diffusion coefficients) and TEM indicate that the
      blue-emitting particles are monodisperse and ball-shaped. Particle size clearly
      determines the emission and excitation spectral region, as expected from quantum
      confinement, but the presence and extent of Si-O species on the silicon networks
      seem crucial for determining the spectrum features and intensity of emission. The
      nanoparticles could hold great potential as quantum dots for applications as
      luminescence sensors in biology and environmental science.

PMID- 22866181
TI  - Graduating High School in a Recession: Work, Education, and Home Production.
AB  - This paper explores how high school graduate men and women vary in their
      behavioral responses to beginning labor market entry during a recession. In
      contrast with previous related literature that found a substantial negative wage
      impact but minimal employment impact in samples of highly educated men, the
      empirical evidence presented here suggests a different outcome for the less well
      educated, and between the sexes. Women, but not men, who graduate high school in
      an adverse labor market are less likely to be in the workforce for the next four
      years, but longer-term effects are minimal. Further, while men increase their
      enrollment as a short-run response to weak labor demand, women do not; instead,
      they appear to temporarily substitute into home production. Women's wages are
      less affected then men's, and both groups' wages are less affected than the
      college graduates previously studied.

PMID- 22866183
TI  - Exploring Lawyer-Client Interaction: A Qualitative Study of Positive Lawyer
      Characteristics.
AB  - Personal injury victims involved in compensation processes have a worse recovery
      than those not involved in compensation processes. One predictor for worse
      recovery is lawyer engagement. As some people argue that this negative relation
      between lawyer engagement and recovery may be explained by lawyers' attitude and
      communications to clients, it seems important to investigate lawyer-client
      interaction. Although procedural justice and therapeutic jurisprudence had
      previously discussed aspects relevant for lawyer-client interaction, the client's
      perspective has been rather ignored and only few empirical studies have been
      conducted. In this qualitative study, 21 traffic accident victims were
      interviewed about their experiences with their lawyer. Five desirable
      characteristics for lawyers were identified: communication, empathy,
      decisiveness, independence, and expertise. Communication and empathy corresponded
      with aspects already discussed in literature, whereas decisiveness, independence
      and expertise had been addressed only marginally. Further qualitative and
      quantitative research is necessary to establish preferable lawyer characteristics
      and to investigate what would improve the well-being of personal injury victims
      during the claims settlement process.

PMID- 22866182
TI  - Enhanced Olfactory Sensory Perception of Threat in Anxiety: An Event-Related fMRI
      Study.
AB  - The current conceptualization of threat processing in anxiety emphasizes
      emotional hyper-reactivity, which mediates various debilitating symptoms and
      derangements in anxiety disorders. Here, we investigated olfactory sensory
      perception of threat as an alternative causal mechanism of anxiety. Combining an
      event-related functional magnetic resonance imaging paradigm with an olfactory
      discrimination task, we examined how anxiety modulates basic perception of
      olfactory threats at behavioral and neural levels. In spite of subthreshold
      presentation of negative and neutral odors, a positive systematic association
      emerged between negative odor discrimination accuracy and anxiety levels. In
      parallel, the right olfactory primary (piriform) cortex indicated augmented
      response to subthreshold negative (vs. neutral) odors as a function of individual
      differences in anxiety. Using a psychophysiological interaction analysis, we
      further demonstrated amplified functional connectivity between the piriform
      cortex and emotion-related regions (amygdala and hippocampus) in response to
      negative odor, particularly in anxiety. Finally, anxiety also intensified skin
      conductance response to negative (vs. neutral) odor, indicative of potentiated
      emotional arousal to subliminal olfactory threat in anxiety. Together, these
      findings elucidate exaggerated processing of olfactory threat in anxiety across
      behavioral, autonomic physiological, and neural domains. Critically, our data
      emphasized anxiety-related hyper-sensitivity of the primary olfactory cortex and
      basic olfactory perception in response to threat, highlighting neurosensory
      mechanisms that may underlie the deleterious symptoms of anxiety.

PMID- 22866184
TI  - Large sacrococcygeal teratoma hindering vaginal delivery attempted at home.
AB  - Sacrococcygeal teratoma in fetus is rare. If it remains antenatally undiagnosed,
      it may cause sudden arrest of an otherwise uncomplicated vaginal delivery because
      of the tumor mass. This poses a challenge to obstetricians. In this era of
      widespread antenatal care, this type of complication is very rare; however, in
      such cases, if met unexpectedly, an urgent laparotomy followed by a reduction of
      the tumor mass might help in completion of the delayed delivery.

PMID- 22866185
TI  - Infectious morbidity after cesarean delivery: 10 strategies to reduce risk.
AB  - Puerperal infection remains a major cause of maternal morbidity and mortality.
      The primary risk factor is cesarean delivery, which increases the risk 5- to 20
      fold. This article reviews in detail the risk of puerperal infection following
      cesarean delivery, both endometritis and surgical site infection, in both high-
      and low-risk populations. Strategies to prevent such infections are also
      discussed using a systematic evidence-based approach.

PMID- 22866186
TI  - Treatment of hyperemesis gravidarum.
AB  - Hyperemesis gravidarum, or pernicious vomiting of pregnancy, is a complication of
      pregnancy that affects various areas of the woman's health, including
      homeostasis, electrolytes, and kidney function, and may have adverse fetal
      consequences. Recent research now provides additional guidelines for protection
      against and relief from hyperemesis gravidarum. Alterations to maternal diet and
      lifestyle can have protective effects. Medicinal methods of prevention and
      treatment include nutritional supplements and alternative methods, such as
      hypnosis and acupuncture, as well as pharmacotherapy.

PMID- 22866187
TI  - Congenital cystic lesions of the lung: congenital cystic adenomatoid malformation
      and bronchopulmonary sequestration.
AB  - Congenital cystic lesions of the lung in fetuses are rare. The most common
      malformations of the lower respiratory tract are congenital cystic adenomatoid
      malformation and bronchopulmonary sequestration. With the increased use of
      obstetric ultrasound, cystic lung lesions are detected more often antenatally,
      which allows for proper planning of peripartum and neonatal management. This
      article discusses a range of diagnostic and management options.

PMID- 22866188
TI  - Pregnancy-associated breast cancer.
AB  - Breast cancer is the second most common malignancy affecting pregnancy. Pregnancy
      associated breast cancer (PABC) is defined as breast cancer diagnosed during
      pregnancy or in the first postpartum year. Because PABC is a relatively rare
      event surrounded by multiple variables, few studies address the best management
      and treatment options. We present a case of PABC to illustrate and highlight some
      of the recommendations for treatment, obstetric care, delivery management, and
      cancer surveillance.

PMID- 22866189
TI  - Premature delivery and the millennium development goal.
AB  - Worldwide, approximately 15 million babies (1 in 10) are born prematurely each
      year. Prematurity is the leading cause of death among newborns, accounting for 1
      million deaths per year, and, after pneumonia, is the second leading cause of
      death in children under age 5 years. Newborns who do survive preterm delivery
      (PTD) struggle with visual, auditory, and learning disabilities. In order to
      reach the fourth Millennium Development Goal (MDG-4) of reducing the mortality
      rate in children under age 5 years by two-thirds between 1990 and 2015, there
      must be significantly fewer PTDs. In high-income nations, 50% of babies born at
      24 weeks survive, whereas in low-resource nations, this survival rate is not
      achieved until 32 weeks of gestation. Over 90% of babies born in low-resource
      settings before 28 weeks die in the first few days of life (< 10% die in high
      income nations), a 10:90 survival gap. Over 60% of PTDs worldwide occur in Sub
      Saharan Africa and South Asia. Risk factors for PTD include adolescent pregnancy,
      short interval between births, poor prepregnancy weight (very low or high body
      mass index), chronic diseases (diabetes and hypertension), infectious disease,
      substance abuse, cervical incompetence, and poor psychological health. Thus, a
      commitment to improving maternal health and the quality of prenatal care is
      necessary to achieve the MDG-4.

PMID- 22866190
TI  - Ureteral injury in laparoscopic gynecologic surgery.
AB  - The introduction of laparoscopy to gynecologic surgery has allowed for both
      innovative advancements and new challenges in the field. As the complexity of
      laparoscopically approached gynecologic cases continues to increase, it is
      imperative for surgeons to be aware of the risk of ureteral injury. Although
      rare, ureteral complications with gynecologic surgery may be quite morbid;
      therefore, knowledge about their prevention, diagnosis, and management is of the
      utmost importance.

PMID- 22866191
TI  - Medical treatment of fibroids.

PMID- 22866192
TI  - Selective serotonin reuptake inhibitors and neonatal anomalies.

PMID- 22866193
TI  - Induction of labor.

PMID- 22866194
TI  - Hypertension control in pregnancy.

PMID- 22866195
TI  - Snippets.

PMID- 22866196
TI  - Navigating International, Interdisciplinary, and Indigenous Collaborative
      Inquiry: Phase 1 in the Circumpolar Indigenous Pathways to Adulthood Project.
AB  - This report describes how multiple community constituents came together to work
      with university researchers on developing a shared agenda for studying young
      indigenous people in five international circumpolar communities. The paper
      focuses on the set up and process of an initial face-to-face methodological
      planning workshop involving youth and adult community members and academics.
      Members of Yup'ik, Inupiat, Eveny, Inuit and Sami communities from Siberia to
      Norway participated in the workshop and engaged in negotiations to arrive at
      shared research interests. This was essential since the ultimate goal of the
      research is translational and transformative, spurring social action in
      communities. Describing the beginning stage of this project and the underlying
      participatory methodology offers reader insight into the how the approach engaged
      community members with varying degrees of sustained interest and practical
      success. It, therefore, articulates a methodological approach for those
      interested in doing community-based participatory research in international
      contexts.

PMID- 22866197
TI  - Monographs editor.

PMID- 22866198
TI  - Vascular Network Formation in Expanding versus Static Tissues: Embryos and
      Tumors.
AB  - In this perspectives article, we review scientific literature regarding de novo
      formation of vascular networks within tissues undergoing a significant degree of
      motion. Next, we contrast dynamic pattern formation in embryos to the
      vascularization of relatively static tissues, such as the retina. We argue that
      formation of primary polygonal vascular networks is an emergent process, which is
      regulated by biophysical mechanisms. Dynamic empirical data, derived from quail
      embryos, show that vascular beds readily form within a moving extracellular
      matrix (ECM) microenvironment-which we analogize to the de novo vascularization
      of small rapidly growing tumors. Our perspective is that the biophysical rules,
      which govern cell motion during vasculogenesis, may hold important clues to
      understanding how the first vessels form in certain malignancies.

PMID- 22866199
TI  - Vascular precursor cells.
AB  - Understanding the mechanisms that regulate the proliferation and differentiation
      of human stem and progenitor cells is critically important for the development
      and optimization of regenerative medicine strategies. For vascular regeneration
      studies, specifically, a true "vascular stem cell" population has not yet been
      identified. However, a number of cell types that exist endogenously, or can be
      generated or propagated ex vivo, function as vascular precursor cells and can
      participate in and/or promote vascular regeneration. Herein, we provide an
      overview of what is known about the regulation of their differentiation
      specifically toward a vascular endothelial cell phenotype.

PMID- 22866201
TI  - Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in
      Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies.
AB  - The vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been
      shown to play major roles not only in physiological but also in most pathological
      angiogenesis, such as cancer. VEGF belongs to the PDGF supergene family
      characterized by 8 conserved cysteines and functions as a homodimer structure.
      VEGF-A regulates angiogenesis and vascular permeability by activating 2
      receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk1 in mice). On the other hand,
      VEGF-C/VEGF-D and their receptor, VEGFR-3 (Flt-4), mainly regulate
      lymphangiogenesis. The VEGF family includes other interesting variants, one of
      which is the virally encoded VEGF-E and another is specifically expressed in the
      venom of the habu snake (Trimeresurus flavoviridis). VEGFRs are distantly related
      to the PDGFR family; however, they are unique with respect to their structure and
      signaling system. Unlike members of the PDGFR family that strongly stimulate the
      PI3K-Akt pathway toward cell proliferation, VEGFR-2, the major signal transducer
      for angiogenesis, preferentially utilizes the PLCgamma-PKC-MAPK pathway for
      signaling. The VEGF-VEGFR system is an important target for anti-angiogenic
      therapy in cancer and is also an attractive system for pro-angiogenic therapy in
      the treatment of neuronal degeneration and ischemic diseases.

PMID- 22866200
TI  - Molecular mechanisms of tumor angiogenesis.
AB  - Tumors have been recently recognized as aberrant organs composed of a complex
      mixture of highly interactive cells that in addition to the cancer cell include
      stroma (fibroblasts, adipocytes, and myofibroblasts), inflammatory (innate and
      adaptive immune cells), and vascular cells (endothelial and mural cells). While
      initially cancer cells co-opt tissue-resident vessels, the tumor eventually
      recruits its own vascular supply. The process of tumor neovascularization
      proceeds through the combined output of inductive signals from the entire
      cellular constituency of the tumor. During the last two decades, the
      identification and mechanistic outcome of signaling pathways that mediate tumor
      angiogenesis have been elucidated. Interestingly, many of the genes and signaling
      pathways activated in tumor angiogenesis are identical to those operational
      during developmental vascular growth, but they lack feedback regulatory control
      and are highly affected by inflammatory cells and hypoxia. Consequently, tumor
      vessels are abnormal, fragile, and hyperpermeable. The lack of hierarchy and
      inconsistent investment of mural cells dampen the ability of the vessels to
      effectively perfuse the tumor, and the resulting hypoxia installs a vicious cycle
      that continuously perpetuates a state of vascular inefficiency. Pharmacological
      targeting of blood vessels, mainly through the VEGF signaling pathway, has proven
      effective in normalizing tumor vessels. This normalization improves perfusion and
      distribution of chemotherapeutic drugs with resulting tumor suppression and
      moderate increase in overall survival. However, resistance to antiangiogenic
      therapy occurs frequently and constitutes a critical barrier in the inhibition of
      tumor growth. A concrete understanding of the chief signaling pathways that
      stimulate vascular growth in tumors and their cross-talk will continue to be
      essential to further refine and effectively abort the angiogenic response in
      cancer.

PMID- 22866202
TI  - Notch signaling in developmental and tumor angiogenesis.
AB  - The discovery that Notch, a key regulator of cell fate determination, is
      functional in the vasculature has greatly improved our understanding of
      differentiation and specialization of vessels. Notch signaling has been proven to
      be critical for arterial specification, sprouting angiogenesis, and vessel
      maturation. In newly forming vascular sprouts, Notch promotes the distinction
      between the leading "tip" endothelial cell and the growing "stalk" cell, the
      endothelial cells that eventually form a new capillary. Notch signaling has also
      been implicated in vessel stability by regulating vascular mural cell function.
      More recently, macrophages carrying an activated Notch have been implicated in
      shaping the course of new sprout formation. Tumor vessels abide by similar
      principles and use Notch signaling in similar ways. An exciting discovery, made
      by several researchers, shows that blocking Notch function in tumor vasculature
      provides a means by which to suppress tumor growth. The authors discuss the
      developmental and physiological role of Notch in the vasculature and apply this
      knowledge to an overview of how Notch targeting in the tumor environment can
      affect tumor angiogenesis and growth.

PMID- 22866204
TI  - Emerging Role of Micro-RNAs in the Regulation of Angiogenesis.
AB  - During development, angiogenesis occurs as a controlled series of events leading
      to neovascularization that supports changing tissue requirements. Several pro-
      and antiangiogenic factors orchestrate a complex, dynamic process to allow
      initial sprouting and invasion, subsequent pruning and remodeling, and finally
      maturation and survival of blood vessels. In the last decade, a new class of
      small RNA molecules termed micro-RNAs (miRs) have emerged as key regulators of
      several cellular processes including angiogenesis. Micro-RNAs such as miR-132,
      miR-126, miR-296, miR-145, and miR-92a have been shown to play pro- and
      antiangiogenic roles in the vasculature of both endothelial cells and
      perivascular cells. However, in pathological situations such as cancer or
      inflammation, the same angiogenic signaling pathways and miRs are dysregulated
      and exploited, typically resulting in poorly organized vessels with leaky and
      tortuous properties. This article is a brief overview of specific miRs that have
      been reported to play a role in the vasculature. The authors explore emerging
      principles that suggest miRs insulate cellular processes from external
      perturbations and provide robustness to biological systems in the context of
      angiogenesis.

PMID- 22866203
TI  - Hypoxia-induced angiogenesis: good and evil.
AB  - The vascular network delivers oxygen (O(2)) and nutrients to all cells within the
      body. It is therefore not surprising that O(2) availability serves as a primary
      regulator of this complex organ. Most transcriptional responses to low O(2) are
      mediated by hypoxia-inducible factors (HIFs), highly conserved transcription
      factors that control the expression of numerous angiogenic, metabolic, and cell
      cycle genes. Accordingly, the HIF pathway is currently viewed as a master
      regulator of angiogenesis. HIF modulation could provide therapeutic benefit for a
      wide array of pathologies, including cancer, ischemic heart disease, peripheral
      artery disease, wound healing, and neovascular eye diseases. Hypoxia promotes
      vessel growth by upregulating multiple pro-angiogenic pathways that mediate key
      aspects of endothelial, stromal, and vascular support cell biology.
      Interestingly, recent studies show that hypoxia influences additional aspects of
      angiogenesis, including vessel patterning, maturation, and function. Through
      extensive research, the integral role of hypoxia and HIF signaling in human
      disease is becoming increasingly clear. Consequently, a thorough understanding of
      how hypoxia regulates angiogenesis through an ever-expanding number of pathways
      in multiple cell types will be essential for the identification of new
      therapeutic targets and modalities.

PMID- 22866205
TI  - The role of stromal myofibroblast and extracellular matrix in tumor angiogenesis.
AB  - Tumor angiogenesis, the building of blood vessels in an expanding tumor mass, is
      an elegantly coordinated process that dictates tumor growth and progression.
      Stromal components of the tumor microenvironment, such as myofibroblasts and the
      extracellular matrix, collaborate with tumor cells in regulating development.
      Such myofibroblasts and the extracellular matrix have ever-expanding roles in the
      angiogenic process as well. This review summarizes how stromal myofibroblasts and
      the extracellular matrix can modulate tumor angiogenesis, highlighting recent
      findings.

PMID- 22866207
TI  - Cilengitide: a prototypic integrin inhibitor for the treatment of glioblastoma
      and other malignancies.
AB  - Integrins are critical intermediaries in a wide spectrum of cancer cell
      activities and thus represent a highly attractive target in oncology therapy.
      Nonetheless, successful exploitation of anti-integrin therapeutics has proven
      challenging to date for cancer patients. In this review, we will focus on
      cilengitide, an RGD pentapeptide inhibitor of alpha V integrins. Although several
      integrin inhibitors are under clinical evaluation, cilengitide is the most
      clinically advanced and is emerging as a prototype for this class of anticancer
      therapy. A foundation of encouraging preclinical studies led to a well-designed
      clinical development plan that culminated in a pivotal phase III study of
      cilengitide in combination with radiation therapy and temozolomide chemotherapy
      for newly diagnosed glioblastoma patients. Accrual to this study recently
      completed, while phase II studies of cilengitide are ongoing for head and neck
      cancer as well as lung cancer. Important future considerations for cilengitide
      and other integrin-targeting agents will likely include the identification of
      optimal combinatorial regimens and the delineation of biomarkers associated with
      efficacy.

PMID- 22866208
TI  - Bicyclic Cyclohexenones as Inhibitors of NF-kappaB Signaling.
AB  - A series of structurally simplified cryptocaryone analogues were synthesized by a
      facile Pd-catalyzed acetoxylation of alkyne-tethered cyclohexadienones and
      evaluated as inhibitors of NF-kappaB signaling. Compounds 10 and 11 were found to
      possess low micromolar inhibitory properties towards induced NF-kappaB activity
      by blocking p50/p65 nuclear protein through a covalent inhibition mechanism. Both
      compounds were able to inhibit NF-kappaB-induced IL-8 expression and exhibited
      antiproliferative activity against two model cancer cell lines. These analogues
      constitute a promising new scaffold for the development of novel NF-kappaB
      inhibitors and anticancer agents.

PMID- 22866206
TI  - Lymphangiogenesis and cancer.
AB  - Historically, lymphatic vessels were considered passive participants in tumor
      metastasis by simply providing channels for tumor cells to transit to draining
      lymph nodes. The discovery of several key lymphatic-specific molecular markers
      and an increased availability of in vitro and in vivo experimental systems to
      study lymphatic biology have however highlighted a much more complex, active role
      for the lymphatic vasculature in metastatic tumor spread. This review will
      briefly describe the lymphatic system and lymphangiogenesis and then focus on the
      role of the lymphatic system in cancer metastasis. The progression of our
      understanding from the lymphatic system as a somewhat passive conduit for
      metastasis to an active participant in metastatic tumor dissemination, regulated
      by a complex array of lymphangiogenic factors, chemokines, and immune cell
      subsets, will be described.

PMID- 22866209
TI  - Unraveling A Trap-and-Trigger Mechanism in the pH-Sensitive Self-Assembly of
      Spider Silk Proteins.
AB  - When the major ampulate spidroins (MaSp1) are called upon to form spider dragline
      silk, one of nature's most amazing materials, a small drop in pH must occur.
      Using a state-of-the-art simulation technique, constant pH molecular dynamics, we
      discovered a few residues that respond to the pH signal in the dimerization of
      the N-terminal domain (NTD) of MaSp1 which is an integral step in the fiber
      assembly. At neutral pH the deprotonation of Glu79 and Glu119 leads to water
      penetration and structural changes at the monomer-monomer binding interface. At
      strongly acidic pH, the protonation of Asp39 and Asp40 weakens the electrostatic
      attraction between the monomers. Thus, we propose a "trap-and-trigger" mechanism
      whereby the intermolecular salt-bridges at physiologically relevant pH conditions
      always act as a stabilizing "trap" favoring dimerization. As pH is lowered to
      about 6, Glu79 and Glu119 become protonated, triggering the dimerization and
      subsequent silk formation. We speculate that this type of mechanism is operative
      in many other pH-sensitive biological processes.

PMID- 22866210
TI  - Near-infrared image-guided laser ablation of artificial caries lesions.
AB  - Laser removal of dental hard tissue can be combined with optical, spectral or
      acoustic feedback systems to selectively ablate dental caries and restorative
      materials. Near-infrared (NIR) imaging has considerable potential for the optical
      discrimination of sound and demineralized tissue. The objective of this study was
      to test the hypothesis that two-dimensional NIR images of demineralized tooth
      surfaces can be used to guide CO(2) laser ablation for the selective removal of
      artificial caries lesions. Highly patterned artificial lesions were produced by
      submerging 5 * 5 mm(2) bovine enamel samples in demineralized solution for a 9
      day period while sound areas were protected with acid resistant varnish. NIR
      imaging and polarization sensitive optical coherence tomography (PS-OCT) were
      used to acquire depth-resolved images at a wavelength of 1310-nm. An imaging
      processing module was developed to analyze the NIR images and to generate optical
      maps. The optical maps were used to control a CO(2) laser for the selective
      removal of the lesions at a uniform depth. This experiment showed that the
      patterned artificial lesions were removed selectively using the optical maps with
      minimal damage to sound enamel areas. Post-ablation NIR and PS-OCT imaging
      confirmed that demineralized areas were removed while sound enamel was conserved.
      This study successfully demonstrated that near-IR imaging can be integrated with
      a CO(2) laser ablation system for the selective removal of dental caries.

PMID- 22866211
TI  - Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR)
      Following Bladder Warming.
AB  - BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to
      renal scarring in children. Current VUR detection involves traumatic x-ray
      imaging of kidneys following injection of contrast agent into bladder via
      invasive Foley catheter. We present an alternative non-invasive approach for
      detecting VUR by radiometric monitoring of kidney temperature while gently
      warming the bladder.  METHODS: We report the design and testing of: i) 915MHz
      square slot antenna array for heating bladder, ii) EMI-shielded log spiral
      microstrip receive antenna, iii) high-sensitivity 1.375GHz total power
      radiometer, iv) power modulation approach to increase urine temperature relative
      to overlying perfused tissues, and v) invivo porcine experiments characterizing
      bladder heating and radiometric temperature of aaline filled 30mL balloon
      "kidney" implanted 3-4cm deep in thorax and varied 2-6 degrees C from core
      temperature.  RESULTS: SAR distributions are presented for two novel antennas
      designed to heat bladder and monitor deep kidney temperatures radiometrically. We
      demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44
      degrees C while maintaining overlying tissues <38 degrees C using time-modulated
      square slot antennas coupled to the abdomen with room temperature water pad.
      Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues
      for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6
      degrees C changes of 30mL "kidney" targets at depth in 34 degrees C invivo pig
      thorax.  CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder
      without toxicity while a 1.375GHz radiometer with log spiral receive antenna
      detects >=2 degrees C rise in 30mL "urine" located 3-4cm deep in thorax,
      demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of
      warmed urine for non-invasive detection of VUR.

PMID- 22866212
TI  - Dose reduction by moving a region of interest (ROI) beam attenuator to follow a
      moving object of interest.
AB  - Region-of-interest (ROI) fluoroscopy takes advantage of the fact that most
      neurovascular interventional activity is performed in only a small portion of an
      x-ray imaging field of view (FOV). The ROI beam filter is an attenuating material
      that reduces patient dose in the area peripheral to the object of interest. This
      project explores a method of moving the beam-attenuator aperture with the object
      of interest such that it always remains in the ROI. In this study, the ROI
      attenuator, which reduces the dose by 80% in the peripheral region, is mounted on
      a linear stage placed near the x-ray tube. Fluoroscopy is performed using the
      Microangiographic Fluoroscope (MAF) which is a high-resolution, CCD-based x-ray
      detector. A stainless-steel stent is selected as the object of interest, and is
      moved across the FOV and localized using an object-detection algorithm available
      in the IMAQ Vision package of LabVIEW. The ROI is moved to follow the stent
      motion. The pixel intensities are equalized in both FOV regions and an adaptive
      temporal filter dependent on the motion of the object of interest is implemented
      inside the ROI. With a temporal filter weight of 5% for the current image in the
      peripheral region, the SNR measured is 47.8. The weights inside the ROI vary
      between 10% and 33% with a measured SNR of 57.9 and 35.3 when the object is
      stationary and moving, respectively. This method allows patient dose reduction as
      well as maintenance of superior image quality in the ROI while tracking the
      object.

PMID- 22866213
TI  - Current status of laparoendoscopic single-site surgery in urologic surgery.
AB  - Since the introduction of laparoscopic surgery, the promise of lower
      postoperative morbidity and improved cosmesis has been achieved. Laparoendoscopic
      single-site surgery (LESS) potentially takes this further. Following the first
      human urological LESS report in 2007, numerous case series have emerged, as well
      as comparative studies comparing LESS with standard laparoscopy. However,
      comparative series between conventional laparoscopy and LESS for different
      procedures suggest a non-inferiority of LESS over standard laparoscopy, but the
      only objective benefit remains an improved cosmetic outcome. Challenging
      ergonomics, instrument clashing, lack of true triangulation, and in-line vision
      are the main concerns with LESS surgery. Various new instruments have been
      designed, but only experienced laparoscopists and well-selected patients are
      pivotal for a successful LESS procedure. Robotic-assisted LESS procedures have
      been performed. The available robotic platform remains bulky, but development of
      instrumentation and application of robotic technology are expected to define the
      actual role of these techniques in minimally invasive urologic surgery.

PMID- 22866214
TI  - Extended pelvic lymph node dissection: before or after radical cystectomy? A
      multicenter study of the Turkish society of urooncology.
AB  - PURPOSE: We aimed to ascertain the effects of performing extended pelvic lymph
      node dissection (PLND) on the duration of surgery, morbidity, and the number of
      lymph nodes removed when the dissection was performed before or after radical
      cystectomy (RC). MATERIALS AND METHODS: We used the database of our previous
      prospective multicenter study. A total of 118 patients underwent RC and extended
      PLND. Of the 118 patients, 48 (40.7%) underwent extended PLND before RC (group 1)
      and 70 (59.3%) underwent extended PLND after RC (group 2). The two groups were
      compared for extended PLND time, RC time, and total operation times, per
      operative morbidity, and the total numbers of lymph nodes removed. RESULTS:
      Clinical and pathologic characteristics were comparable in the two groups
      (p>0.05). The mean RC time and mean total operation times were significantly
      shorter in group 1 than in group 2 (p<0.001). The mean number of lymph nodes
      removed was 27.31+/-10.36 in group 1 and 30.87+/-8.3 in group 2 (p=0.041). Only
      at the presacral region was the mean number of lymph nodes removed significantly
      fewer in group 1 than in group 2 (p=0.001). Intraoperative and postoperative
      complications and drain withdrawal time were similar in both groups (p=0.058,
      p=0.391, p=0.613, respectively). CONCLUSIONS: When extended PLND was performed
      before RC, the duration of RC and consequently the total duration of the
      operation were significantly shorter than when extended PLND was performed after
      RC. Practitioners may consider performing extended PLND before RC and rechecking
      the presacral area for additional lymph nodes after RC, particularly in elderly
      patients with high co-morbidity for whom the duration of surgery matters.

PMID- 22866215
TI  - Multivariate analysis of the prognostic significance of resection weight after
      transurethral resection of bladder tumor for non-muscle-invasive bladder cancer.
AB  - PURPOSE: Tumor size and multiplicity are known to be important prognostic factors
      in non-muscle-invasive bladder cancer (NMIBC). However, evaluation of accurate
      tumor size is subjective and difficult. Furthermore, there are limitations to the
      objectification of tumor volume in the case of multiple lesions. In this study,
      we investigated the relation between resection weight after transurethral
      resection of bladder tumor (TURBT) and the prognosis of NMIBC. MATERIALS AND
      METHODS: This was a retrospective analysis of 406 patients diagnosed with pTa or
      pT1 bladder tumors after TURBT between September 1999 and May 2010. The patient's
      age, sex, underlying diseases, cancer stage, grade, multiplicity, tumor size,
      lymphovascular invasion, and resection weight were analyzed in relation to cancer
      progression and recurrence. The resection weight was weighted after formaldehyde
      fixation. RESULTS: The mean follow-up time was 76.9 months (range, 12 to 167
      months) in 406 patients diagnosed as having NMIBC. Mean resection weight was 4.5
      g (range, 0.1 to 35.0 g). The cancer recurred in 99 patients (24.4%), and disease
      progression was noted in 30 patients (7.4%). Resection weight was categorized as
      greater than or less than 2 g by use of receiver operator characteristic curves.
      Cancer grade (p=0.022) and multiplicity (p=0.043) were significantly related to
      cancer recurrence in the analysis with Cox's multivariate proportional hazard
      model. Cancer grade (p=0.001) and resection weight (p=0.018) were related to
      disease progression. CONCLUSIONS: Resection weight after TURBT was significantly
      related to progression of NMIBC. Resection weight was an independent factor of
      progression. Further management should be considered if the resection weight
      exceeds 2 g.

PMID- 22866216
TI  - Impact of prostate size on pathologic outcomes and prognosis after radical
      prostatectomy.
AB  - PURPOSE: We investigated prostate size and its correlation with final pathologic
      outcomes and prognosis. MATERIALS AND METHODS: From 1993 to 2009, 830 consecutive
      patients who underwent radical prostatectomy with follow-up duration of 12 months
      or more were included in this study. Patients were categorized according to
      prostate size as follows: group 1, prostate size <=40 g (n=458), and group 2,
      prostate size >40 g (n=472). Preoperative parameters and postoperative pathologic
      outcomes were compared between groups. Multivariate analysis with Cox
      proportional hazards regression model was used to identify the pathologic and
      clinical factors affecting biochemical recurrence. RESULTS: Patients in group 1
      had higher pathologic T stage (pT2a=17.7% vs. 23.9%, pT2b=1.1% vs. 0%, pT2c=40.4%
      vs. 39.8%, pT3a=29.5% vs. 21.0%, pT3b=10.7% vs. 13.2%, p=0.003) and higher
      positive surgical margin (40.3% vs. 33.1%, p=0.033) than did patients in group 2.
      Pathologic Gleason score was not significantly different between the two groups.
      The 5-year biochemical-recurrence-free survival was 62.3% for patients in group 1
      and 73.2% for patients in group 2 (p=0.005). Multivariate Cox regression analysis
      showed that prostate size of 40 g or less (hazard ratio [HR], 1.378; 95%
      confidence interval [CI], 1.027 to 1.848; p=0.032), extracapsular extension (HR,
      1.592; 95% CI, 1.147 to 2.209; p=0.005), positive surgical margin (HR, 2.348; 95%
      CI, 1.701 to 3.242; p<0.001), and pathologic Gleason sum (HR, 1.507; 95% CI,
      1.292 to 1.758; p<0.001) were independent predictors of biochemical recurrence.
      CONCLUSIONS: Smaller prostate size was associated with increased risk of higher
      pT stage and positive surgical margin after radical prostatectomy. Also, prostate
      size less than 40 g was an independent prognostic factor for biochemical
      recurrence.

PMID- 22866217
TI  - Role of prostate-specific antigen change ratio at initial biopsy as a novel
      decision-making marker for repeat prostate biopsy.
AB  - PURPOSE: Prostate biopsy is used to confirm the prostate cancer. Although first
      biopsy result was benign, repeat biopsy is recommended for the patient who has
      higher risk of prostate cancer. In this study, we investigated the PSA change
      ratio (post-biopsy PSA to baseline PSA) whether it could be predictive factor of
      prostate cancer and helpful when decided to perform repeat biopsy. MATERIALS AND
      METHODS: 151 patients, first diagnosed as benign, but underwent repeat biopsy due
      to clinical suspicion of prostate cancer were included. Post-biopsy PSA was
      checked 60 minutes later after biopsy. PSA change ratio was defined as post
      biopsy PSA to baseline PSA. According to results of repeat biopsy, patients were
      divided into benign group (group A) and cancer groups (group B). Between two
      group baseline PSA, PSA density, post-biopsy PSA and PSA change ratio were
      compared, and most effective cut-off value was analyzed using receiver operating
      characteristic (ROC). RESULTS: 129 men were benign, 22 men were prostate cancer
      according to results of repeat biopsy. Between two groups, post-biopsy PSA and
      PSA change ratio were statically significant differences. (p<0.001, <0.001) The
      effective cut-off value was 3.0, 3.5 and 4.0 according to ROC. At ROC curve, PSA
      change ratio was statistically significant for diagnosis of prostate cancer. (AUC
      0.800, p<0.001). CONCLUSIONS: PSA change ratio is thought be a predictive factor
      for prostate cancer. If the PSA change ratio was less than 3.0-4.0, repeat biopsy
      should be considered to confirm the diagnosis.

PMID- 22866218
TI  - Influence of intravesical prostatic protrusion on preoperative lower urinary
      tract symptoms and outcomes after 120 w high performance system laser treatment
      in men with benign prostatic hyperplasia.
AB  - PURPOSE: To evaluate the efficacy of photoselective vaporization of the prostate
      (PVP) with the 120 W Greenlight high performance system (HPS) laser for the
      treatment of benign prostatic hyperplasia (BPH) with intravesical prostatic
      protrusion (IPP). MATERIALS AND METHODS: This study was conducted on 389 BPH
      patients who underwent PVP with the 120 W HPS laser from April 2009 to August
      2011. The patients were divided into groups according to IPP: group I was defined
      as IPP of 0 to 5 mm (n=216), group II as IPP of 5 to 10 mm (n=135), and group III
      as IPP above 10 mm (n=38). Prostate volume, prostate-specific antigen,
      International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax),
      and postvoid residual volume (PVR) were assessed and checked at postoperative 1,
      3, 6, and 12 months. RESULTS: There was a significant difference in the mean
      prostate size in each group (p<0.05). The preoperative total IPSS score, IPSS
      voiding symptom score, and quality of life score were not significantly
      different. However, the IPSS storage symptom score was significantly different
      between groups 1 and 2 and group 3. IPSS scores, Qmax, and PVR at postoperative
      1, 3, 6, and 12 months showed significant improvement compared with preoperative
      values. CONCLUSIONS: The degree of IPP can affect storage symptoms. However,
      there is no significant correlation between the degree of IPP and postoperative
      results. Also, the degree of IPP does not affect short- and long-term PVP
      results. Proper elimination of bladder outlet obstruction is important for
      symptomatic relief.

PMID- 22866219
TI  - Relationship between Intravesical Prostatic Protrusion and Postoperative Outcomes
      in Patients with Benign Prostatic Hyperplasia.
AB  - PURPOSE: To evaluate the significance of intravesical prostatic protrusion (IPP)
      for predicting postoperative outcomes in patients with benign prostatic
      hyperplasia. MATERIALS AND METHODS: A total of 177 patients with a possible
      follow-up of at least 6 months who were treated with transurethral resection of
      the prostate (TURP) were analyzed. We divided the patients into two groups on the
      basis of the degree of IPP: the significant IPP group (IPP>=5 mm, n=74) and the
      no significant IPP group (IPP<5 mm, n=103). We analyzed postoperative changes in
      parameters, such as the International Prostate Symptom Score (IPSS), IPSS quality
      of-life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual
      urine (PVR). The IPSS was subdivided into voiding (IPSS-v) and storage (IPSS-s)
      symptoms. Multivariate logistic regression analysis was performed to identify
      whether IPP could predict surgical outcomes of TURP. RESULTS: Preoperative
      parameters were not significantly different between the two groups except for
      total prostate volume and transitional zone volume. Postoperative changes in
      IPSS, IPSS-v, IPSS-s, and QoL score were higher in the significant IPP group than
      in the group with no significant IPP. Changes in Qmax and PVR were not
      significantly different between the two groups. Multivariate logistic regression
      analysis (after adjustment for age, prostate-specific antigen level, total
      prostate volume, and transitional zone volume) revealed that the odds ratios (95%
      confidence interval) of decreased IPSS and IPSS-s in the significant IPP group
      were 3.43 (1.03 to 11.44) and 3.51 (1.43 to 8.63), respectively (p=0.045 and
      0.006, respectively). CONCLUSIONS: Significant IPP is an independent factor for
      predicting better postoperative outcomes of IPSS and IPSS-s.

PMID- 22866220
TI  - Clinical efficacy in the treatment of overactive bladder refractory to
      anticholinergics by posterior tibial nerve stimulation.
AB  - PURPOSE: Overactive bladder (OAB) is a clinical syndrome that is currently
      treated initially with anticholinergics, although some other therapeutic
      alternatives exist, such as neuromodulation, botulinum toxin, and posterior
      tibial nerve stimulation (PTNS). The purpose of this study was to assess the
      efficacy of PTNS in patients with OAB refractory to anticholinergics. MATERIALS
      AND METHODS: We present a cohort study of 14 women with OAB to whom we applied
      PTNS. We assessed (before and after the treatment) the diurnal micturitional
      frequency, the nocturnal micturitional frequency, urgency episodes, and urge
      incontinence episodes. Results were analyzed by using the Wilcoxon test for
      nonparametric samples. RESULTS: We observed statistically significant improvement
      in the diurnal micturitional frequency (p=0.05), in episodes of micturitional
      urgency (p=0.03), and in episodes of urge incontinence (p=0.004). A total of 50%
      of the patients felt subjective improvement from their pathology. CONCLUSIONS:
      PTNS is a valid, minimally invasive treatment option with minimum morbidity for
      patients with OAB refractory to treatment with anticholinergics.

PMID- 22866221
TI  - Bladder Wall Thickness is Associated with Responsiveness of Storage Symptoms to
      Alpha-Blockers in Men with Lower Urinary Tract Symptoms.
AB  - PURPOSE: Bladder wall thickness (BWT) is reported to be related to detrusor
      overactivity and bladder outlet obstruction. We investigated the relationship
      between BWT and the responsiveness of storage symptoms to alpha-blockers in men
      with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 74
      patients with LUTS were enrolled. International Prostate Symptom Score,
      uroflowmetry with post-void residual urine volume, and transrectal
      ultrasonography (TRUS) were investigated. BWT was measured by performing TRUS at
      the midsagittal plane view, and the average value of BWT at the anterior, dome,
      and trigone areas was used. After 4 weeks of alpha-blocker medication, patients
      were reevaluated and divided into two groups. The responder group consisted of
      patients who reported improvement in the storage symptom subscore of 2 points or
      more; the non-responder group consisted of patients who reported improvement of
      less than 2 points. Clinical parameters including BWT were compared between the
      two groups. RESULTS: A total of 52 patients were followed. BWT was positively
      correlated with intravesical prostate protrusion (IPP) (9.26+/-4.99, standardized
      beta=0.393, p=0.002) and storage symptom subscore (0.35+/-0.43, standardized
      beta=0.458, p=0.002). Compared with that in the responder group, BWT was thicker
      in the non-responder group, and improvement in the storage symptom score was
      correlated with BWT (0.58+/-0.09 cm vs. 0.65+/-0.11 cm, p=0.018) and prostate
      volume (27.08+/-16.26 ml vs. 36.44+/-10.1 ml, p=0.018). CONCLUSIONS: BWT was
      correlated with IPP, the storage symptom subscore, and the responsiveness of
      storage symptoms to alpha-blockers in LUTS/benign prostatic hyperplasia (BPH)
      patients. As BWT increased, the responsiveness of storage symptoms to alpha
      blocker decreased in LUTS/BPH patients.

PMID- 22866222
TI  - Fragmented pigtail percutaneous nephrostomy tubes: etiology and management.
AB  - PURPOSE: To review our experience with the management of fragmented and retained
      pigtail percutaneous nephrostomy (PCN) tubes and to explore the reasons for the
      fragmentation. MATERIALS AND METHODS: We retrospectively reviewed our institute
      database from January 2006 to December 2011 for patients who had undergone
      retrieval of fragmented PCN tubes. We assessed the preoperative factors,
      operative technique, and post-operative outcomes. RESULTS: A total of seven
      patients (4 males and 3 females) had been diagnosed with fragmented PCN tubes.
      The mean age of the patients was 41.5 years. Of the seven patients, five required
      antegrade instrumentation by way of a percutaneous tract to remove the foreign
      body, mostly along with stone retrieval. One patient underwent ureterorenoscopy
      and pneumolithotripsy for a ureteric stone along with ureteroscopic removal of
      the PCN fragment. Another patient underwent nephrectomy of the kidney containing
      the PCN fragment because it had become nonfunctioning. All patients were free of
      stones and symptoms on follow-up. CONCLUSIONS: A prolonged waiting period for
      definitive surgery, urinary infection, and associated stone disease are
      significant factors causing fragmentation of PCN tubes. Proper insertion
      techniques, regular timed changes of the PCN tube, appropriate care of the PCN
      tube, and early surgery for underlying stone disease are required to avoid this
      complication. Patients with retained PCN tubes can be managed effectively with
      antegrade or retrograde endoscopic techniques while definitive management of the
      primary pathology is carried out, without any additional morbidity.

PMID- 22866223
TI  - Therapeutic efficacy of bipolar radiofrequency thermotherapy for patients with
      chronic prostatitis: a retrospective analysis of 26 cases.
AB  - PURPOSE: Chronic prostatitis (CP) does not yet have a universally successful
      therapy. Alternative treatments including thermotherapy have been adopted in the
      multimodal management of pain and voiding dysfunction. We retrospectively
      analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for
      patients who were unsatisfied with conventional medication for CP. MATERIALS AND
      METHODS: A retrospective study between October 2009 and September 2010 of 26
      patients who were under 50 years old and diagnosed with CP (National Institutes
      of Health [NIH]-category III) was performed. Twenty patients were diagnosed with
      inflammatory CP (NIH-category IIIa) and the rest with noninflammatory CP (NIH
      category IIIb). We used the Tempro system at an intraprostatic temperature of 55C
      for 50 minutes with a medium heating rate. All patients also completed the NIH
      Chronic Prostatitis Symptom Index (CPSI) before and after treatment. RESULTS: In
      the patients diagnosed with CP, the mean serum prostate-specific antigen (PSA)
      level was 0.9+/-0.3 ng/ml, the prostate volume was 27.1+/-5.5 g, and the average
      score for all 3 domains on the NIH-CPSI significantly decreased. The total scores
      decreased from 19.8+/-7.1 to 11.1+/-7.0, the pain domain decreased from 8.6+/-3.1
      to 4.8+/-3.1, the voiding symptom domain decreased from 5.1+/-1.8 to 2.9+/-1.8,
      and the effect on the quality of life decreased from 6.1+/-2.2 to 3.4+/-2.2
      (p<0.05). CONCLUSIONS: Bipolar radiofrequency thermotherapy for patients with CP
      intractable to conventional medication can provide significant improvement in the
      NIH-CPSI. Large, randomized controlled trials will also be required to confirm
      the efficacy of this therapy.

PMID- 22866224
TI  - Bilateral ureteral stones and spontaneous perirenal hematoma in a patient with
      chronic idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an immune thrombocytopenia with a
      usually benign clinical course. Bleedings are mostly of the mucocutaneous type
      with mild symptoms. Massive bleedings requiring transfusion are rarely seen,
      unless the number of platelets decreases to extremely low levels. In this case,
      bilateral perirenal hematoma and bilateral distal ureteral stones were detected
      on a non-contrast computed tomography scan of a 57-year-old male patient who
      developed macroscopic hematuria during his treatment in the clinics of internal
      medicine because of left flank pain and diffuse petechial rashes all over his
      body. The patient, who had been receiving chronic ITP treatment for 1 year, had a
      very low platelet count (4,000/mm(3)). The patient was prescribed bed rest, and
      his platelet count increased to a safe level for surgical intervention of above
      50,000/mm(3) with administration of prednisolone, intravenous immune globulin,
      and platelet suspension. A stone-free state was achieved after bilateral
      ureterorenoscopy and pneumatic lithotripsy. A conservative approach was followed
      for the perirenal hematoma. Upon regression of the perirenal hematoma, the
      patient was discharged at 9 weeks postoperatively.

PMID- 22866225
TI  - Anterior urethral valve and diverticulum in a neonate with febrile urinary tract
      infection.
AB  - Anterior urethral valve is a rare congenital anomaly that can cause obstructive
      uropathy. Herein, we report a case of an anterior urethral valve that led to the
      development of febrile urinary tract infection in a neonate.

PMID- 22866226
TI  - Medical ultrasound systems.
AB  - Medical ultrasound imaging has advanced dramatically since its introduction only
      a few decades ago. This paper provides a short historical background, and then
      briefly describes many of the system features and concepts required in a modern
      commercial ultrasound system. The topics addressed include array beam formation,
      steering and focusing; array and matrix transducers; echo image formation; tissue
      harmonic imaging; speckle reduction through frequency and spatial compounding,
      and image processing; tissue aberration; Doppler flow detection; and system
      architectures. It then describes some of the more practical aspects of ultrasound
      system design necessary to be taken into account for today's marketplace. It
      finally discusses the recent explosion of portable and handheld devices and their
      potential to expand the clinical footprint of ultrasound into regions of the
      world where medical care is practically non-existent. Throughout the article
      reference is made to ways in which ultrasound imaging has benefited from advances
      in the commercial electronics industry. It is meant to be an overview of the
      field as an introduction to other more detailed papers in this special issue.

PMID- 22866227
TI  - Ultrasonic colour Doppler imaging.
AB  - Ultrasonic colour Doppler is an imaging technique that combines anatomical
      information derived using ultrasonic pulse-echo techniques with velocity
      information derived using ultrasonic Doppler techniques to generate colour-coded
      maps of tissue velocity superimposed on grey-scale images of tissue anatomy. The
      most common use of the technique is to image the movement of blood through the
      heart, arteries and veins, but it may also be used to image the motion of solid
      tissues such as the heart walls. Colour Doppler imaging is now provided on almost
      all commercial ultrasound machines, and has been found to be of great value in
      assessing blood flow in many clinical conditions. Although the method for
      obtaining the velocity information is in many ways similar to the method for
      obtaining the anatomical information, it is technically more demanding for a
      number of reasons. It also has a number of weaknesses, perhaps the greatest being
      that in conventional systems, the velocities measured and thus displayed are the
      components of the flow velocity directly towards or away from the transducer,
      while ideally the method would give information about the magnitude and direction
      of the three-dimensional flow vectors. This review briefly introduces the
      principles behind colour Doppler imaging and describes some clinical
      applications. It then describes the basic components of conventional colour
      Doppler systems and the methods used to derive velocity information from the
      ultrasound signal. Next, a number of new techniques that seek to overcome the
      vector problem mentioned above are described. Finally, some examples of vector
      velocity images are presented.

PMID- 22866228
TI  - Three-dimensional ultrasound scanning.
AB  - The past two decades have witnessed developments of new imaging techniques that
      provide three-dimensional images about the interior of the human body in a manner
      never before available. Ultrasound (US) imaging is an important cost-effective
      technique used routinely in the management of a number of diseases. However, two
      dimensional viewing of three-dimensional anatomy, using conventional two
      dimensional US, limits our ability to quantify and visualize the anatomy and
      guide therapy, because multiple two-dimensional images must be integrated
      mentally. This practice is inefficient, and may lead to variability and incorrect
      diagnoses. Investigators and companies have addressed these limitations by
      developing three-dimensional US techniques. Thus, in this paper, we review the
      various techniques that are in current use in three-dimensional US imaging
      systems, with a particular emphasis placed on the geometric accuracy of the
      generation of three-dimensional images. The principles involved in three
      dimensional US imaging are then illustrated with a diagnostic and an
      interventional application: (i) three-dimensional carotid US imaging for
      quantification and monitoring of carotid atherosclerosis and (ii) three
      dimensional US-guided prostate biopsy.

PMID- 22866229
TI  - Quantitative contrast-enhanced ultrasound imaging: a review of sources of
      variability.
AB  - Ultrasound provides a valuable tool for medical diagnosis offering real-time
      imaging with excellent spatial resolution and low cost. The advent of microbubble
      contrast agents has provided the additional ability to obtain essential
      quantitative information relating to tissue vascularity, tissue perfusion and
      even endothelial wall function. This technique has shown great promise for
      diagnosis and monitoring in a wide range of clinical conditions such as
      cardiovascular diseases and cancer, with considerable potential benefits in terms
      of patient care. A key challenge of this technique, however, is the existence of
      significant variations in the imaging results, and the lack of understanding
      regarding their origin. The aim of this paper is to review the potential sources
      of variability in the quantification of tissue perfusion based on microbubble
      contrast-enhanced ultrasound images. These are divided into the following three
      categories: (i) factors relating to the scanner setting, which include
      transmission power, transmission focal depth, dynamic range, signal gain and
      transmission frequency, (ii) factors relating to the patient, which include body
      physical differences, physiological interaction of body with bubbles, propagation
      and attenuation through tissue, and tissue motion, and (iii) factors relating to
      the microbubbles, which include the type of bubbles and their stability,
      preparation and injection and dosage. It has been shown that the factors in all
      the three categories can significantly affect the imaging results and contribute
      to the variations observed. How these factors influence quantitative imaging is
      explained and possible methods for reducing such variations are discussed.

PMID- 22866230
TI  - Real-time quasi-static ultrasound elastography.
AB  - Ultrasound elastography is a technique used for clinical imaging of tissue
      stiffness with a conventional ultrasound machine. It was first proposed two
      decades ago, but active research continues in this area to the present day.
      Numerous clinical applications have been investigated, mostly related to cancer
      imaging, and though these have yet to prove conclusive, the technique has seen
      increasing commercial and clinical interest. This paper presents a review of the
      most widely adopted, non-quantitative, techniques focusing on technical
      innovations rather than clinical applications. The review is not intended to be
      exhaustive, concentrating instead on placing the various techniques in context
      according to the authors' perspective of the field.

PMID- 22866231
TI  - Vascular ultrasound for atherosclerosis imaging.
AB  - Cardiovascular disease is a leading cause of death in the Western world.
      Therefore, detection and quantification of atherosclerotic disease is of
      paramount importance to monitor treatment and possible prevention of acute
      events. Vascular ultrasound is an excellent technique to assess the geometry of
      vessel walls and plaques. The high temporal as well as spatial resolution allows
      quantification of luminal area and plaque size and volume. While carotid arteries
      can be imaged non-invasively, scanning of coronary arteries requires invasive
      intravascular catheters. Both techniques have already demonstrated their clinical
      applicability. Using linear array technology, detection of disease as well as
      monitoring of pharmaceutical treatment in carotid arteries are feasible. Data
      acquired with intravascular ultrasound catheters have proved to be especially
      beneficial in understanding the development of atherosclerotic disease in
      coronary arteries. With the introduction of vascular elastography not only the
      geometry of plaques but also the risk for rupture of plaques might be identified.
      These so-called vulnerable plaques are frequently not flow-limiting and rupture
      of these plaques is responsible for the majority of cerebral and cardiac
      ischaemic events. Intravascular ultrasound elastography studies have demonstrated
      a high correlation between high strain and vulnerable plaque features, both ex
      vivo and in vivo. Additionally, pharmaceutical intervention could be monitored
      using this technique. Non-invasive vascular elastography has recently been
      developed for carotid applications by using compound scanning. Validation and
      initial clinical evaluation is currently being performed. Since abundance of vasa
      vasorum (VV) is correlated with vulnerable plaque development, quantification of
      VV might be a unique tool to even prevent this from happening. Using ultrasound
      contrast agents, it has been demonstrated that VV can be identified and
      quantified. Although far from routine clinical application, non-invasive and
      intravascular ultrasound VV imaging might pave the road to prevent
      atherosclerotic disease in an early phase. This paper reviews the conventional
      vascular ultrasound techniques as well as vascular ultrasound strain and vascular
      ultrasound VV imaging.

PMID- 22866232
TI  - Micro-ultrasound for preclinical imaging.
AB  - Over the past decade, non-invasive preclinical imaging has emerged as an
      important tool to facilitate biomedical discovery. Not only have the markets for
      these tools accelerated, but the numbers of peer-reviewed papers in which imaging
      end points and biomarkers have been used have grown dramatically. High frequency
      'micro-ultrasound' has steadily evolved in the post-genomic era as a rapid,
      comparatively inexpensive imaging tool for studying normal development and models
      of human disease in small animals. One of the fundamental barriers to this
      development was the technological hurdle associated with high-frequency array
      transducers. Recently, new approaches have enabled the upper limits of linear and
      phased arrays to be pushed from about 20 to over 50 MHz enabling a broad range of
      new applications. The innovations leading to the new transducer technology and
      scanner architecture are reviewed. Applications of preclinical micro-ultrasound
      are explored for developmental biology, cancer, and cardiovascular disease. With
      respect to the future, the latest developments in high-frequency ultrasound
      imaging are described.

PMID- 22866233
TI  - Biomedical photoacoustic imaging.
AB  - Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical
      imaging modality based on the use of laser-generated ultrasound that has emerged
      over the last decade. It is a hybrid modality, combining the high-contrast and
      spectroscopic-based specificity of optical imaging with the high spatial
      resolution of ultrasound imaging. In essence, a PA image can be regarded as an
      ultrasound image in which the contrast depends not on the mechanical and elastic
      properties of the tissue, but its optical properties, specifically optical
      absorption. As a consequence, it offers greater specificity than conventional
      ultrasound imaging with the ability to detect haemoglobin, lipids, water and
      other light-absorbing chomophores, but with greater penetration depth than purely
      optical imaging modalities that rely on ballistic photons. As well as visualizing
      anatomical structures such as the microvasculature, it can also provide
      functional information in the form of blood oxygenation, blood flow and
      temperature. All of this can be achieved over a wide range of length scales from
      micrometres to centimetres with scalable spatial resolution. These attributes
      lend PA imaging to a wide variety of applications in clinical medicine,
      preclinical research and basic biology for studying cancer, cardiovascular
      disease, abnormalities of the microcirculation and other conditions. With the
      emergence of a variety of truly compelling in vivo images obtained by a number of
      groups around the world in the last 2-3 years, the technique has come of age and
      the promise of PA imaging is now beginning to be realized. Recent highlights
      include the demonstration of whole-body small-animal imaging, the first
      demonstrations of molecular imaging, the introduction of new microscopy modes and
      the first steps towards clinical breast imaging being taken as well as a myriad
      of in vivo preclinical imaging studies. In this article, the underlying physical
      principles of the technique, its practical implementation, and a range of
      clinical and preclinical applications are reviewed.

PMID- 22866234
TI  - Ultrasound-mediated optical tomography: a review of current methods.
AB  - Ultrasound-mediated optical tomography (UOT) is a hybrid technique that is able
      to combine the high penetration depth and high spatial resolution of ultrasound
      imaging to overcome the limits imposed by optical scattering for deep tissue
      optical sensing and imaging. It has been proposed as a method to detect blood
      concentrations, oxygenation and metabolism at depth in tissue for the detection
      of vascularized tumours or the presence of absorbing or scattering contrast
      agents. In this paper, the basic principles of the method are outlined and
      methods for simulating the UOT signal are described. The main detection methods
      are then summarized with a discussion of the advantages and disadvantages of
      each. The recent focus on increasing the weak UOT signal through the use of the
      acoustic radiation force is explained, together with a summary of our results
      showing sensitivity to the mechanical shear stiffness and optical absorption
      properties of tissue-mimicking phantoms.

PMID- 22866236
TI  - Continuous wave ultrasonic Doppler tomography.
AB  - In continuous wave ultrasonic Doppler tomography (DT), the ultrasonic beam moves
      relative to the scanned object to acquire Doppler-shifted frequency spectra which
      correspond to cross-range projections of the scattering and reflecting structures
      within the object. The relative motion can be circular or linear. These data are
      then backprojected to reconstruct the two-dimensional image of the object cross
      section. By using coherent processing, the spatial resolution of ultrasonic DT is
      close to an order of magnitude better than that of traditional pulse-echo imaging
      at the same ultrasound frequency.

PMID- 22866235
TI  - Thermal strain imaging: a review.
AB  - Thermal strain imaging (TSI) or temporal strain imaging is an ultrasound
      application that exploits the temperature dependence of sound speed to create
      thermal (temporal) strain images. This article provides an overview of the field
      of TSI for biomedical applications that have appeared in the literature over the
      past several years. Basic theory in thermal strain is introduced. Two major
      energy sources appropriate for clinical applications are discussed. Promising
      biomedical applications are presented throughout the paper, including non
      invasive thermometry and tissue characterization. We present some of the
      limitations and complications of the method. The paper concludes with a
      discussion of competing technologies.

PMID- 22866237
TI  - Ultrasonic image analysis and image-guided interventions.
AB  - The fields of medical image analysis and computer-aided interventions deal with
      reducing the large volume of digital images (X-ray, computed tomography, magnetic
      resonance imaging (MRI), positron emission tomography and ultrasound (US)) to
      more meaningful clinical information using software algorithms. US is a core
      imaging modality employed in these areas, both in its own right and used in
      conjunction with the other imaging modalities. It is receiving increased interest
      owing to the recent introduction of three-dimensional US, significant
      improvements in US image quality, and better understanding of how to design
      algorithms which exploit the unique strengths and properties of this real-time
      imaging modality. This article reviews the current state of art in US image
      analysis and its application in image-guided interventions. The article concludes
      by giving a perspective from clinical cardiology which is one of the most
      advanced areas of clinical application of US image analysis and describing some
      probable future trends in this important area of ultrasonic imaging research.

PMID- 22866238
TI  - Ultrasonic imaging: safety considerations.
AB  - Modern ultrasound imaging for diagnostic purposes has a wide range of
      applications. It is used in obstetrics to monitor the progress of pregnancy, in
      oncology to visualize tumours and their response to treatment, and, in
      cardiology, contrast-enhanced studies are used to investigate heart function and
      physiology. An increasing use of diagnostic ultrasound is to provide the first
      photograph for baby's album-in the form of a souvenir or keepsake scan that might
      be taken as part of a routine investigation, or during a visit to an independent
      high-street 'boutique'. It is therefore important to ensure that any benefit
      accrued from these applications outweighs any accompanying risk, and to evaluate
      the existing ultrasound bio-effect and epidemiology literature with this in mind.
      This review considers the existing laboratory and epidemiological evidence about
      the safety of diagnostic ultrasound and puts it in the context of current
      clinical usage.

PMID- 22866239
TI  - Barriers to Considering Ethical and Societal Implications of Research:
      Perceptions of Life Scientists.
AB  - BACKGROUND: As part of an empirical study investigating how life scientists think
      about ethical and societal implications of their work, and about life science
      research in general, we sought to elucidate barriers that scientists might face
      in considering such implications.  METHOD: Between 2005 and 2007, we conducted a
      study consisting of phone interviews, focus groups, and a national survey of life
      scientists at biomedical research institutions. The study population included
      graduate students, postdoctoral fellows, faculty, clinical instructors, and
      research staff. We analyzed data through qualitative and quantitative methods. 
      RESULTS: In analyzing the data, we found that life scientists do, in fact, face
      barriers to considering ethical and societal implications of research. We
      categorized these barriers as falling into four broad domains: (1) lack of
      awareness of ethical and societal implications; (2) lack of relevance of such
      concerns to their specific research; (3) self-confidence in their ability to
      resolve such concerns; and (4) aspects of the daily practice of science itself. 
      CONCLUSIONS: Life science researchers experience elements inherent in their
      training and in the conduct of science as barriers to thinking about ethical and
      societal implications related to their work. These findings suggest areas in
      which research ethics educators, bioethicists, and the scientific community can
      focus their efforts to improve social and ethical accountability in research.

PMID- 22866240
TI  - Sexual Attitudes, Reasons for Forgoing Condom Use, and the Influence of Gender
      Power among Asian-American Women: A Qualitative Study.
AB  - BACKGROUND AND PURPOSE: HIV/AIDS prevalence among Asian-American Pacific
      Islanders (APIs) is low yet rapidly increasing. Prior research from other
      populations indicates that HIV risk behaviors are associated with specific
      adverse/risk factors including depression, drug use, history of child sexual
      abuse, and forced sex. However, no studies have explored the attitudes about
      sexual risk behaviors and condom use between API women with adverse experiences
      versus women without such experiences. This qualitative study compares
      descriptions of sexual history and condom use between the two groups of women. 
      METHODS: A random sample of 24 sexually active API women (16 in the adverse group
      and 8 in the non-adverse group) was selected for in-depth interviews from a
      larger study, which included 501 Korean, Chinese, and Vietnamese survey
      participants.  FINDINGS: 14 out of the 16 women in the adverse group described
      complex sexual histories, with greater number of partners, more casual partners,
      and the combined use of alcohol/drugs and sex. The 8 women in the non-adverse
      group had fewer partners who were more long term. However, for both groups of
      women, condom use was inconsistent. Also, the majority of the women in both
      groups reported that either they themselves or they together with their partners
      had decided whether or not to use condoms. Yet 4 women in the adverse group
      showed lower gender power, with their partners being the primary decision-maker
      for condom use.  CONCLUSION: Given the inconsistent condom use for both groups,
      all women in this study were at risk for HIV/AIDS. Consistent with prior
      research, a sub-group of the women in the adverse group with lower gender power
      seemed particularly at higher risk. Future HIV prevention interventions need to
      target all API women while screening for lower gender power to identify those
      with the highest risk of HIV.

PMID- 22866241
TI  - A proteasome inhibitor fails to attenuate dystrophic pathology in mdx mice.
AB  - Dystrophin deficiency leads to increased proteasome activity in skeletal muscle.
      Previous observations suggest short-term inhibition of the proteasome restores
      dystrophin expression. Contrary to our hypothesis, eight days of MG-132
      administration to mdx mice increased susceptibility to contraction induced injury
      and Evan's blue dye penetration compared to controls. Following six weeks of MG
      132 administration muscle function was similar to control animals. These data
      suggest that proteasome inhibition does not reduce the severity of muscle
      dysfunction caused by dystrophin-deficiency.

PMID- 22866242
TI  - Clinic-based infant screening for duchenne muscular dystrophy: a feasibility
      study.
AB  - Purpose. The purpose of this study was to assess the desirability of Duchenne
      muscular dystrophy (DMD) screening, the effectiveness of the consent process, and
      the feasibility of conducting DMD screening in a pediatric office. Methods.
      Infant males who attended a 12-month routine well-child visit at a participating
      pediatric clinic were screened for DMD. Parents and providers completed post
      screening questionnaires to assess their experiences with and attitudes toward
      screening. Results. A total of 264 male infants were screened for DMD.
      Approximately 78% of parents indicated support of voluntary DMD screening and 91%
      of providers were in favor of screening for DMD. About 75% of parents correctly
      answered three of five questions testing their knowledge of DMD screening.
      Conclusion. DMD screening is feasible in a pediatric office when conducted as
      part of a research study. Infant screening for DMD eventually could be offered in
      pediatric health care provider offices as an optional public health service
      outside of newborn screening.

PMID- 22866244
TI  - Facile Synthesis of Clickable, Water-soluble and Degradable Polyphosphoesters.
AB  - "Click" chemistry is a library of efficient and reliable reactions, which have
      been used to functionalize various classes of bio- and synthetic macromolecular
      systems for the incorporation of designed properties and functions. In this
      report, azide-alkyne Huisgen cycloaddition and thiol-yne reactions, two classical
      "click" chemistries, were employed to functionalize biodegradable, clickable
      polyphosphoester homopolymers and their water-soluble copolymers. A stable alkyne
      functionalized phospholane monomer was synthesized, its organocatalyzed
      polymerization kinetics were evaluated, and the resulting (co)polymers were
      utilized to develop this facile method that provides the synthesis of clickable,
      water-soluble and degradable polyphosphoesters, which can be adapted for various
      applications.

PMID- 22866246
TI  - Benign Colonic (18)F-FDG Uptake on Whole-Body FDG-PET Scan.

PMID- 22866245
TI  - Normal tissue protection for improving radiotherapy: Where are the Gaps?
AB  - Any tumor could be controlled by radiation therapy if sufficient dose were
      delivered to all tumor cells. Although technological advances in physical
      treatment delivery have been developed to allow more radiation dose conformity,
      normal tissues are invariably included in any radiation field within the tumor
      volume and also as part of the exit and entrance doses relevant for particle
      therapy. Mechanisms of normal tissue injury and related biomarkers are now being
      investigated, facilitating the discovery and development of a next generation of
      radiation protectors and mitigators. Bringing recent research advances stimulated
      by development of radiation countermeasures for mass casualties, to clinical
      cancer care requires understanding the impact of protectors and mitigators on
      tumor response. These may include treatments that modify cellular damage and
      death processes, inflammation, alteration of normal flora, wound healing, tissue
      regeneration and others, specifically to counter cancer site-specific adverse
      effects to improve outcome of radiation therapy. Such advances in knowledge of
      tissue and organ biology, mechanisms of injury, development of predictive
      biomarkers and mechanisms of radioprotection have re-energized the field of
      normal tissue protection and mitigation. Since various factors, including organ
      sensitivity to radiation, cellular turnover rate, and differences in mechanisms
      of injury manifestation and damage response vary among tissues, successful
      development of radioprotectors/mitigators/treatments may require multiple
      approaches to address cancer site specific needs. In this review, we discuss
      examples of important adverse effects of radiotherapy (acute and intermediate to
      late occurring, when it is delivered either alone or in conjunction with
      chemotherapy, and important limitations in the current approaches of using
      radioprotectors and/or mitigators for improving radiation therapy. Also, we are
      providing general concepts for drug development for improving radiation therapy.

PMID- 22866247
TI  - Is antibiotic resistance microorganism becoming a significant problem in acute
      cholangitis in Korea?

PMID- 22866248
TI  - Gastric preparation for upper endoscopy.

PMID- 22866249
TI  - Introduction; value of endoscopic ultrasound-guided fine needle aspiration.
AB  - Introduction of endoscopic ultrasound (EUS) to medical practice has brought a
      huge change in diagnostic algorithm of many gastrointestinal diseases. Addition
      of EUS-guided fine needle aspiration (FNA) upgraded diagnostic power of EUS. In
      this focused review series, value of EUS-FNA in the diagnosis of various diseases
      and tips for getting the best results with EUS-FNA are described by four invited
      authors including myself. First, Dr. Jeong Seop Moon discussed about EUS-FNA in
      submucosal lesion. He also touched on basic techniques and needles of EUS-FNA in
      his article. Next, I focused on additional value of EUS-FNA in the staging of
      hollow viscus cancer to optimize the treatment strategy. World's well-known
      endosonographer, Dr. Robert H. Hawes kindly presented his profound thoughts on
      EUS-FNA in pancreatic cystic lesions. Dr. Jayapal Ramesh and Dr. Shyam
      Varadarajulu shared their valuable tips for getting the best results when using
      EUS-FNA. Nobody doubts now EUS-FNA is an indispensable procedure in
      gastrointestinal endoscopy. Therefore, this focused review series will provide
      the readers with the concentrated knowledge of "What should we know about EUS
      FNA."

PMID- 22866250
TI  - Endoscopic ultrasound-guided fine needle aspiration in submucosal lesion.
AB  - A submucosal lesion, more appropriately a subepithelial lesion, is hard to
      diagnose. Endoscopic ultrasonography is good to differentiate the nature of
      submucosal lesion. For definite diagnosis, tissue acquisition from submucosal
      lesion is necessary, and many methods have been introduced for this purpose
      mainly by endoscopic ultrasonography, such as endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA), EUS-guided Trucut Biopsy (TCB), and EUS-guided fine
      needle biopsy (FNB). For EUS-FNA, adequate processing of specimen is important,
      and for proper diagnosis of EUS-FNA specimen, both cytologic and histologic
      examinations, including immunohistochemical stains, are important. All
      gastrointestinal stromal tumors have some degree of malignant potential, so there
      have been a lot of efforts and methods to increase diagnostic yields of
      submucosal lesion. We herein review the current hot topics on EUS-FNA for
      submucosal tumor, such as needles, on-site cytopathologists, immunohistochemical
      stains, EUS-TCB, EUS-FNB, Ki-67 labelling index, DOG1, and combining EUS-FNA and
      EUS-TCB.

PMID- 22866251
TI  - Endoscopic ultrasound-guided fine needle aspiration in hollow viscus cancer.
AB  - Accurate cancer staging is essential in patients with hollow viscus malignancy to
      decide therapeutic modalities. Endoscopic ultrasound (EUS) is considered as the
      best modality for local staging of hollow viscus cancer. EUS-guided fine needle
      aspiration (FNA) is a minimally invasive and effective sampling method. EUS-FNA
      should be applied when positive diagnosis of malignancy can possibly change the
      choice of therapeutic options. EUS in conjunction with EUS-FNA can optimize stage
      directed therapy which is helpful in selecting minimally invasive treatment
      option including endoscopic treatment and avoiding unnecessary surgery in
      advanced cases.

PMID- 22866252
TI  - Endoscopic ultrasound-guided fine needle aspiration in cystic pancreatic lesions.
AB  - Incidental pancreatic cysts are being increasingly recognized recently with
      incremented concern about health and frequent health check-up. Endoscopic
      ultrasound (EUS) has emerged as the principal modality for imaging pancreas for
      various pancreatic diseases including pancreatic cyst. But imaging alone cannot
      accurately identify the exact nature of the pancreatic cyst. EUS-guided fine
      needle aspiration is a useful adjunctive procedure to differentiate pancreatic
      cystic lesions. Cystic fluid analysis with cytologic evaluation is important to
      diagnose etiology of pancreatic cystic lesions, helping the clinician to more
      accurately assess the presence or potential for malignancy.

PMID- 22866253
TI  - How can we get the best results with endoscopic ultrasound-guided fine needle
      aspiration?
AB  - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has evolved to
      become an indispensable tool for tissue acquisition. While the overall diagnostic
      accuracy of EUS-FNA is greater than 90% for lung cancer staging, it is lower for
      pancreatic mass lesions. Several factors such as location of the tumor, disease
      characteristics and procedural techniques determine the outcomes of EUS-FNA. In
      this review we evaluate the various technical factors that are keys to attaining
      optimal procedural outcomes.

PMID- 22866254
TI  - Non-steroidal anti-inflammatory drug-induced enteropathy.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly
      prescribed drugs in the world. NSAID-induced lower gastrointestinal (GI)
      complications are increasing while upper GI complications are decreasing. Lower
      GI events accounted for 40% of all serious GI events in patients on NSAIDs.
      Capsule endoscopy and device assisted enteroscopy are available for detection of
      small intestinal lesions. Capsule endoscopy studies have demonstrated that NSAIDs
      use in healthy volunteers raised the incidence (55% to 75%) of intestinal damage.
      It appears that selective cyclooxygenase-2 inhibitors (coxibs) improved upper and
      lower GI safety based on results of clinical trials. Selective coxibs are still
      capable of triggering GI adverse events and cardiovascular toxicity issues were
      the main focus of concerns. Unfortunately, definite strategies are not available
      to prevent or heal NSAID-induced intestinal injuries. Thus, there is still a
      strong clinical need for effective drugs with improved safety profiles than the
      existing NSAIDs.

PMID- 22866255
TI  - The Clinical Meaning of Benign Colon Uptake in (18)F-FDG PET: Comparison with
      Colonoscopic Findings.
AB  - BACKGROUND/AIMS: Benign colon (18)F-fluorodeoxyglucose (FDG) uptake is frequently
      observed in asymptomatic individuals. Aims of this study were to investigate the
      benign colon uptake by whole body FDG-positron emission tomography (PET) in
      asymptomatic adults and to correlate those results with colonoscopic and
      histologic findings. METHODS: Among 3,540 subjects who had undergone FDG-PET, 43
      subjects who were diagnosed to have benign colon uptake in FDG-PET and underwent
      colonoscopy were retrospectively reviewed. Subjects were classified as diffuse or
      focal groups based on their FDG uptake patterns. PET results were analyzed
      together with colonoscopic and histologic findings. RESULTS: Forty-three subjects
      showed benign colon uptake in FDG-PET; 28 of them were shown as the diffuse
      group, while other 15 subjects were classified as the focal group. Five subjects
      among those showed diffuse uptake were diagnosed as adenoma. Seven among 15
      subjects who showed focal uptake were diagnosed as adenocarcinoma (n=2), adenoma
      (n=3), or non-neoplastic polyp (n=2). Positive predictive values were 25% in the
      diffuse group and 47% in the focal group. CONCLUSIONS: We recommend that patients
      showing benign FDG uptake in the colon should be further evaluated by
      colonoscopy, especially for patients with focal FDG uptake.

PMID- 22866256
TI  - Expression of MUC5AC and Trefoil Peptide 1 (TFF1) in the Subtypes of Intestinal
      Metaplasia.
AB  - BACKGROUND/AIMS: Alterations of the expression pattern of mucins and trefoil
      peptides have been described in gastric adenocarcinomas and in their precursor
      lesions. The aim of this study was to determine the progression patterns of
      intestinal metaplasia (IM) subtypes by analyzing the expression patterns of TFF1
      and MUC5AC in different subtypes of IM of the stomach. METHODS: Endoscopic
      gastric biopsies of the antrum and body were obtained from patients with
      dyspepsia and endoscopic IM. Alcian blue/periodic acid-Schiff staining and the
      high iron diamine technique were used to classify the subtypes of IM.
      Immunoreactivity for MUC5AC and TFF1 was estimated in different types of IM.
      RESULTS: IM was detected in 128 samples from 80 patients; type I was found in 48
      samples, type II was found in 37 samples, and type III was found in 43 samples.
      There was a gradual decrease in MUC5AC and TFF1 expression during the progression
      of IM from type I to type III via the type II intermediate. CONCLUSIONS: This
      downregulation of MUC5AC and TFF1 expression may challenge the sequential
      progression of IM from type I to type III via the type II intermediate, and it
      might be associated with gastric carcinogenesis.

PMID- 22866257
TI  - Extended Spectrum-beta-Lactamase or Carbapenemase Producing Bacteria Isolated
      from Patients with Acute Cholangitis.
AB  - BACKGROUND/AIMS: This study assessed the antibiotic resistance organisms isolated
      from the blood and bile of acute cholangitis and evaluated risk factors
      associated with them and their impact on clinical outcomes. METHODS: The
      identities and antibiotic resistance profiles of bacteria isolated from 433 cases
      of acute cholangitis from 346 patients were analyzed. Risk factors and the
      outcomes of patients infected with them were assessed. RESULTS: Microorganisms
      were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures.
      Isolates from bile and blood were identical in 71% of the cases. A total of 20
      extended spectrum-beta-lactamase (ESBL)-producers and 4 carbapenemase-producing
      organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase
      producers were isolated from bile. Sixty-four (14.8%) cases were infected with
      any one of these bacteria isolated from blood or bile. Risk factors associated
      with them in blood were nosocomial infection and prior biliary intervention. In
      bile, indwelling biliary device was a risk factor associated with them.
      Antibiotic-resistant bacteria were associated with mortality, independent of
      other prognostic factors. CONCLUSIONS: ESBL or carbapenemase-producing bacteria
      were frequently isolated in acute cholangitis patients especially with prior
      biliary intervention and nosocomial infection. Isolation of antibiotic-resistant
      bacteria was an independent risk factor of mortality.

PMID- 22866258
TI  - Effectiveness of Premedication with Pronase for Visualization of the Mucosa
      during Endoscopy: A Randomized, Controlled Trial.
AB  - BACKGROUND/AIMS: Gastric mucus should be removed before endoscopic examination to
      increase visibility. In this study, the effectiveness of premedication with
      pronase for improving visibility during endoscopy was investigated. METHODS: From
      April 2010 to February 2011, 400 outpatients were randomly assigned to receive
      endoscopy with one of four premedications as follows: dimethylpolysiloxane
      (DMPS), pronase and sodium bicarbonate with 10 minutes premedication time (group
      A, n=100), DMPS and sodium bicarbonate with 10 minutes premedication time (group
      B, n=100), DMPS, pronase and sodium bicarbonate with 20 minutes premedication
      time (group C, n=100), and DMPS and sodium bicarbonate with 20 minute
      premedication time (group D, n=100). One endoscopist, who was unaware of the
      premedication types, calculated the visibility scores (range, 1 to 3) of the
      antrum, lower gastric body, upper gastric body and fundus. The sum of the scores
      from the four locations was defined as the total visibility score. RESULTS: Group
      C showed significantly lower scores than other groups (p=0.002). Group C also had
      the lowest frequency of flushing, which was significantly lower than that of
      group D. Groups C and D had significantly shorter durations of examination than
      groups A and B. CONCLUSIONS: Using pronase 20 minutes before endoscopy
      significantly improved endoscopic visualization and decreased the frequency of
      water flushing.

PMID- 22866259
TI  - A case of giant lipoma causing chronic recurrent intussusception of the colon.
AB  - Colonic lipomas, which often occur in elderly women, usually have small size and
      occur mainly in the cecum and ascending colon. Most colonic lipomas are
      asymptomatic and identified incidentally at the time of endoscopy or surgery.
      However, they may cause symptoms such as bleeding, obstruction or intussusception
      as their size increases. Intermittent episodes of intussusception are uncommon
      but may be caused by large pedunculated lipoma. In a 68-year-old woman suffering
      intermittent abdominal pain, 5.5*4.5*3.8-cm huge mass was found by colonoscopy at
      proximal ascending colon, which was intussuscepted to proximal transverse colon
      on abdominal computed tomography. Segmental right colonic resection was
      conducted. We report a case of symptomatic giant pedunculated colonic lipoma
      causing intussusception requiring surgical intervention, with a successful
      recovery after surgery.

PMID- 22866260
TI  - Successful treatment of early gastric cancer adjacent to a fundal varix by
      endoscopic submucosal dissection and endoscopic cyanoacrylate therapy.
AB  - Endoscopic submucosal dissection (ESD) was developed for the en bloc resection of
      large early gastrointestinal neoplasms. A disadvantage of ESD is its technical
      difficulty, which requires advanced skills and is associated with a higher rate
      of complications. Endoscopic variceal obturation (EVO) using cyanoacrylate has
      emerged as the initial treatment of choice for acute gastric variceal bleeding.
      This procedure achieves hemostasis in 90% of cases. A 52-year-old patient with
      Child A alcoholic liver cirrhosis presented with early gastric cancer in the
      cardia and type 1 isolated gastric varices in the fundus. The two lesions were so
      close together that treatment was not easy. The lesions were managed successfully
      with a combination of ESD and EVO using cyanoacrylate.

PMID- 22866261
TI  - Cecal fecaloma due to intestinal tuberculosis: endoscopic treatment.
AB  - Colorectal fecaloma is a mass of accumulated feces that is much harder in
      consistency than a fecal impactation. The rectosigmoid area is the common site
      for fecalomas and the cecum is the most unusual site. Diagnosis is usually made
      by distinctive radiographic findings of a mobile intraluminal mass with a smooth
      outline and no mucosal attachment. Most of the fecalomas are successfully treated
      by conservative methods such as laxatives, enemas and rectal evacuation. When
      conservative treatments have failed, endoscopic procedures or a surgical
      intervention may be needed. We report here that a cecal fecaloma caused by
      intestinal tuberculosis scar was successfully removed by endoscopic procedures.

PMID- 22866262
TI  - A case of ampullary perforation treated with a temporally covered metal stent.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is
      classified into three or four types based on anatomical location and the
      mechanism of injury. Although ampullary injury, among them, may be managed
      nonsurgically, surgical management is required in cases of perforation with
      retroperitoneal fluid collection and severe condition. Here, a patient with ERCP
      related severe ampullary perforation with retroperitoneal fluid collection that
      was treated nonsurgically with a covered stent is presented.

PMID- 22866263
TI  - Three to Tango: MUC1 as a Ligand for Both E-Selectin and ICAM-1 in the Breast
      Cancer Metastatic Cascade.
AB  - CANCER CELL TETHERING AND ROLLING ON THE VASCULAR WALL IS FACILITATED BY VARIOUS
      SELECTIN: glycoprotein interactions which lead to eventual extravasation and
      metastases. The aberrantly underglycosylated mucin MUC1 has been shown to both
      abundantly express selectin binding moieties (sialyl Lewis x and a) and to
      consistently expose its core epitope. Flow cytometry was used to determine MUC1
      expression on ZR-75-1 and MCF7 cells, while immunofluorescence microscopy was
      used to confirm the aberrant form of MUC1 and MUC1:ICAM-1 interactions. Each cell
      line was then perfused through combined E-selectin and ICAM-1 coated microtubes,
      as a model of the microvascular endothelium. ZR-75-1 and MCF7 were found to
      express abundant and low levels of underglycosylated MUC1, respectively. The
      rolling/adhesion profiles showed that ZR-75-1 cells, when compared to MCF7 cells,
      interact with E-selectin more efficiently resulting in sufficiently slow rolling
      velocities to form MUC1:ICAM-1 interactions thereby facilitating firm adhesion.
      The purpose and novelty of this work is the demonstration of the synergistic
      adhesion capabilities of MUC1 in the metastatic adhesion cascade, where the
      observed differential adhesion is consistent with the relative metastatic
      potential of the ZR-75-1 (highly metastatic) and MCF7 (weakly metastatic) cell
      lines.

PMID- 22866264
TI  - The emerging role of fumarate as an oncometabolite.
AB  - The drive to understand how altered cellular metabolism and cancer are linked has
      caused a paradigm shift in the focus of cancer research. The discovery of a
      mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation
      of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence
      that dysfunctional metabolism plays an important role in oncogenesis. Striking
      parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumor
      suppressor, whose mutation is associated with the development of leiomyomata,
      renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of
      intracellular fumarate which has been proposed to act as a competitive inhibitor
      of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor
      (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our
      studies have questioned the role of HIF and have highlighted other candidate
      mechanisms, in particular the non-enzymatic modification of cysteine residues
      (succination) that could lead to disruption or loss of protein functions,
      dysfunctional cell metabolism and cell signaling. Here, we discuss the evidence
      for proposing fumarate as an onco-metabolite.

PMID- 22866266
TI  - The Glu727 Allele of Thyroid Stimulating Hormone Receptor Gene is Associated with
      Osteoporosis.
AB  - BACKGROUND: Published data indicate that thyroid stimulating hormone receptor
      (TSHR) activities are associated with osteoporosis in some patients. AIM: This
      study aimed to elucidate whether a given polymorphism of the TSHR gene is
      associated with osteoporosis. MATERIALS AND METHODS: One hundred and fifty
      subjects with osteoporosis were recruited in this study. The diagnosis of
      osteoporosis was performed with quantitative ultrasound system. The TSHR gene
      polymorphism was examined by polymerase chain reaction-restriction fragment
      length polymorphism. RESULTS: The results showed a nucleotide substitution in the
      first position of codon 36 of the TSHR gene. The nucleotide substitution was from
      G to C, leading to a (36)D -> (36)H change (D36H) in the predicted amino acid
      sequence of the receptor. The change did not show significance between healthy
      subjects and patients with osteoporosis (P > 0.05). On the other hand, we
      identified another single nucleotide polymorphism that is a C-to-G substitution
      at codon 727 (GAC to GAG); its frequency was significantly higher in patients
      with osteoporosis than that in healthy subjects. Using logistic regression
      analysis, significant correlation was revealed between the genotype D727E and the
      serum levels of TSH, or the quantitative ultrasound value of the calcaneal bone.
      CONCLUSIONS: The present study suggests that the genotype D727E of the TSHR, but
      not the genotype D36H, may be a genetic risk factor for osteoporosis.

PMID- 22866265
TI  - Diagnosis and management of gallbladder cancer.
AB  - Gallbladder cancer (GBC) is a rather uncommon disease, but at the time when it
      gives symptoms it has usually reached no longer curable stage. Therefore, all
      attempts must be made to make the diagnosis earlier to have better opportunity
      for cure. The author searched PubMed, and reviewed literatures on diagnoses and
      treatment of GBC.

PMID- 22866267
TI  - Prevalence of malnutrition among the mising children of northeast India: a
      comparison between four different sets of criteria.
AB  - BACKGROUND: Prevalence of malnutrition among the children from developing
      countries has reached unprecedented level which can be evaluated by body mass
      index. AIM: This study was designed to determine the prevalence of malnutrition
      among the Mising children of Northeast India using four different sets of Body
      Mass Index references. MATERIALS AND METHODS: A cross-sectional study was
      performed on a population representative sample of 511 Mising children. Four
      different sets of Body Mass Index reference were used to define thinness as well
      as overweight cases. RESULTS: With the use of different references the prevalence
      of thinness varies from 17.18% to 27.73% among the boys and from 19.21% to 28.23%
      among the girls. On the other hand the prevalence of overweight varies from 1.95%
      to 7.81% among the boys and 1.96% to 9.41% among the girls. Reference based on
      United States (1971-74) survey detects sex difference in overweight. The
      calculated kappa values indicated a fair to almost perfect agreement between
      various references. CONCLUSION: Considerable prevalence of overweight despite a
      persistently high burden of thinness suggests existence of nutrition transition
      among the Mising population. Prevalence of malnutrition differs with the
      application of different references which warrants application of international
      references carefully for any potential misclassification of children.

PMID- 22866268
TI  - Blood Glucose Control and Medication Adherence Among Adult Type 2 Diabetic
      Nigerians Attending A Primary Care Clinic in Under-resourced Environment of
      Eastern Nigeria.
AB  - BACKGROUND: Despite the evidence that goal blood glucose control reduces
      preventable emergency hospitalizations, the control of blood glucose has been
      variable in Nigeria. AIM: The study was designed to determine the blood glucose
      control and medication adherence among adult type 2 diabetic Nigerians attending
      a primary care clinic in under-resourced environment of Eastern Nigeria.
      MATERIALS AND METHODS: A cross-sectional study was carried out on 120 adult type
      2 diabetic patients who were on treatment for at least 3 months at the primary
      care clinic of Federal Medical Centre, Umuahia. A patient was said to have a goal
      blood glucose control if the fasting blood glucose was 70-130 mg/dL. Adherence
      was assessed in the previous 30 days using pretested, interviewer-administered
      questionnaire on self-reported therapy. Operationally, an adherent patient was
      one who scored 4 points in the previous 30 days. The reasons for non-adherence
      were documented. RESULTS: The blood glucose control and medication adherence
      rates were 61.7% and 72.5%, respectively. Blood glucose control was significantly
      associated with adherence to treatment (P=0.025) and medication duration >=3
      years (P=0.045). The most common reason for non-adherence was financial
      constraints (P=0.033). CONCLUSION: Glycaemic control and medication adherence
      among the study population were good and should constitute logical targets for
      intervention.

PMID- 22866269
TI  - Antibiotic susceptibility patterns of uropathogens in obstetric patients.
AB  - BACKGROUND: Urinary tract infections (UTI) are the most commonly encountered
      infections in obstetric patients. Although a variety of etiology is involved,
      Escherichia coli and other coliforms account for a large majority of these
      naturally acquired infections. The estimation of local etiology and
      susceptibility profile could support the most effective empirical treatment. AIM:
      The current study was undertaken to find the spectrum of micro-organisms
      responsible for causing UTI in obstetric patients and to find out the most
      appropriate antibiotic. MATERIALS AND METHODS: Consecutive patients in different
      stages of pregnancy with or without symptoms of UTI attending the antenatal
      clinic during November 2011 to March 2012 were screened for significant
      bacteriuria. The bacterial uropathogens isolated were then subjected to
      antimicrobial susceptibility testing and screened for ESBL production and
      methicillin resistance. RESULTS: During the 5-month study period, out of the 250
      samples screened, a total of 60 (24%) samples of urine from pregnant females, in
      different stages of pregnancy were found to be positive on culture. The
      Enterobacteriaceae accounted for nearly two-thirds of the isolates and E. coli
      alone accounted for 63% of the urinary isolates followed by Klebsiella pneumonia
      8%. Among the Gram-positive cocci, coagulase-negative Staphylococcus (15%) were
      more frequently isolated than Staphylococcus aureus (8.3%). A significantly high
      resistance was noted to the beta-lactam group of antimicrobials, fluoroquinolones
      and cotrimoxazole, both by the Gram-negative bacilli as well as Gram-positive
      cocci. Resistance was quite low against the aminoglycosides and nitrofurantoin
      and virtually absent against imipenem. CONCLUSION: The susceptibility patterns
      seen in our study seem to suggest that it is absolutely necessary to obtain
      sensitivity reports before initiation of antibiotic therapy in cases of suspected
      UTI.

PMID- 22866270
TI  - Cyanoacrylate glue dressing for hypospadias surgery.
AB  - BACKGROUND: Hypospadias repair is a common pediatric operation. Several kinds of
      dressings are currently available, with their benefits and side effects. AIM: The
      aim of our study was to introduce a new method of dressing, by pouring several
      layers of cyanoacrylate (CA) glue as the dressing, in hypospadias surgery.
      MATERIALS AND METHODS: Twenty out of the 61 patients with hypospadias, with a
      mean age of 13.5 months, were enrolled in this study. Forty-one had conventional
      dressing (pressure wrap dressing), while CA glue was used in 20 patients. CA glue
      was applied around the penis and its base four times and each time it took one
      minute to dry. All patients were followed postoperatively for two weeks and six
      to twelve months, for early and late complications, respectively. RESULTS: One
      out of 20 developed wound hematoma, one had skin necrosis with infection, and
      edema was present in all. All these were easily diagnosed and managed rapidly. In
      the group treated with conventional methods, there were five infections, seven
      hematomas, all the patients in the group had edema and painful removal of the
      dressing, and 10 needed repeat dressing. CONCLUSIONS: CA glue is impermeable to
      urine and stool, and prevents edema and hematoma. Used in several layers, it is a
      good alternative dressing in hypospadias surgery.

PMID- 22866271
TI  - Applications of cyanoacrylate glue in pediatric urology.

PMID- 22866272
TI  - Hidden diagnosis in the subglottic larynx: schwannoma mimicking as bronchial
      asthma.
AB  - Schwannomas are rare neurogenic tumors derived from the schwann cells. Their
      laryngeal location is uncommon and the diagnosis is difficult. We report a case
      of a 17-year-old female who presented with symptoms of intermittent
      breathlessness mimicking acute attacks of bronchial asthma and resulted in
      delayed diagnosis, which lead to upper airway obstruction and an emergency
      tracheostomy. Computed tomography (CT) of neck revealed a soft-tissue mass within
      the subglottic region. Surgical excision of the growth was done by laryngofissure
      technique. Histopathological examination of the tumor revealed it to be a
      schawanoma. The subglottic occurrence of schwannoma is very rare. Case history
      and detailed clinical examination are important and will guide for relevant
      investigations and help to reach at a definitive diagnosis.

PMID- 22866273
TI  - Type 3B Malrotation Presented with Acute Appendicitis as Left Renal Colic.
AB  - Midgut malrotation is a rare anatomic anomaly that complicates the diagnosis and
      managemant of acute abdominal pain. It is a congenital anomaly that arises from
      incomplete rotation or abnormal position of the midgut during embryonic
      development. We report a case of a patient who have very rare form (Nonrotation
      of the proximal loop associated with partial rotation of the distal loop) of
      malrotation with ruptured appendicitis. Left-sided acute appendicitis should be
      considered in the differential diagnosis of patients with pain with localized in
      the left lower quadrant.

PMID- 22866274
TI  - Stigma and Therapy Completion for Latent Tuberculosis among Haitian-origin
      Patients.
AB  - A prospective cohort study of LTBI treatment conducted within the Haitian
      population of South Florida investigated the predictive association between
      illness-related stigma among patients near the beginning of treatment and
      completion of preventive therapy. Factors associated with perceived stigma were
      also investigated. Ninety patients from Broward and Palm Beach counties were
      administered a questionnaire that included items related to illness history,
      perceptions and understanding of latent tuberculosis, and a 25-item stigma scale
      adapted from previously developed measures of tuberculosis-related stigma.
      Therapy completion was determined through a follow-up chart review. Data analyses
      compared patients who completed therapy with those who defaulted on a number of
      variables including perceived stigma. No association was found between perceived
      stigma or demographic characteristics and adherence to preventive therapy.
      Perceived stigma was associated with patient report of illness-related distress
      and was higher among patients who were lost to follow up. Some evidence suggested
      that stigma was higher among contacts of cases, patients with limited
      understanding of the condition, and patients who were more closely monitored
      during treatment. Case management should focus on patient-centered approaches to
      education and counseling about LTBI that address patient understanding of the
      condition and concerns about its physical and psychosocial effects.

PMID- 22866276
TI  - Point-of-care platforms for salivary diagnostics.
AB  - Saliva reflects the physiologic state of the body, including emotional,
      endocrinal, nutritional and metabolic variations, and so can be used to monitor
      both oral and systemic health. In the past decade, salivary diagnostic approaches
      have been developed to monitor oral and systemic diseases. Along with these
      exciting scientific advancements, there is an emerging need to move salivary
      diagnostics out of the lab and into clinical practice. Point-of-care (POC)
      technologies specifically developed for salivary diagnostics can provide rapid,
      simple, low-cost and accurate measurements directly from saliva. To further
      transform salivary diagnostics into clinical reality, an integrated platform
      based POC application is necessary, which includes sample processing, detection,
      a user-friendly interface and medical information technology. This review
      presents the requirements for POC platforms in salivary diagnostics and describes
      current applications of POC platforms for monitoring medical conditions using
      saliva. By advancing POC platforms for salivary diagnostics, dentists are
      anticipated to engage in chairside screening of medical conditions.

PMID- 22866277
TI  - The relationship between temporomandibular joint ankylosis and condylar
      fractures.
AB  - Trauma is the predominant causal factor for temporomandibular joint (TMJ)
      ankylosis. However, the relationship between condylar fracture and TMJ ankylosis
      is complicated. It is believed that post-traumatic TMJ ankylosis arises from TMJ
      intracapsular changes, including damaged cartilage, displaced or disrupted discs,
      haematoma formation and subsequent fibrosis and calcification in the joint. In
      this review, the relationship between TMJ ankylosis and condylar fracture is
      discussed based on clinical characteristics and animal studies. The management of
      TMJ ankylosis is also reviewed and discussed.

PMID- 22866278
TI  - Contralateral full-thickness retroangular flap for the reconstruction of
      midfacial through-and-through defects following skin cancer ablation.
AB  - OBJECTIVE: To explore the use of the contralateral full-thickness retroangular
      island flap for reconstructing midfacial through-and-through defects. METHODS:
      Full-thickness retroangular flaps raised from the contralateral infraorbital
      region were used to reconstruct midfacial through-and-through defects in eight
      patients following the resection of skin cancers. The defects ranged in size from
      4.5 * 5.5 cm to 6.0 * 8.0 cm (mean 5.78 * 6.06 cm). The skin and mucosa in the
      full-thickness flaps ranged in size from 3.0 * 9.0 cm to 4.0 * 12.0 cm (mean 3.50
      * 10.25 cm) and from 2.0 * 2.0 cm to 2.5 * 3.0 cm (mean 2.19 * 2.69 cm),
      respectively. RESULTS: All the flaps survived and no complications occurred. The
      patients were followed for an average of 9.0 months (range 6-13 months). The
      vascularity of the flaps was good and the colour and texture matches were
      excellent. Cosmetic and functional outcomes were satisfactory in all patients.
      CONCLUSION: The contralateral full-thickness retroangular island flap containing
      the angular vessels in the pedicle is technically simple to use and is a good
      alternative for the reconstruction of moderate to large midfacial through-and
      through defects.

PMID- 22866279
TI  - Lipoprotein-associated phospholipase A2 and serum lipid levels in subjects with
      chronic periodontitis and hyperlipidemia.
AB  - OBJECTIVE: To evaluate the relationships between clinical periodontal parameters
      and levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and lipid profile
      markers in subjects with or without hyperlipidaemia. METHODS: Forty chronic
      periodontitis (CP) subjects with hyperlipidaemia (CP/HPL group), 40 systemically
      healthy CP subjects (CP group) and 20 systemically and periodontally healthy
      subjects (control group) were enrolled. The clinical periodontal parameters, the
      serum concentrations of Lp-PLA2, lipid profiles including total cholesterol (TC),
      triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density
      lipoprotein cholesterol (LDL-c) and white blood cell (WBC) counts were determined
      and compared between different groups. Linear regression analysis was performed
      to identify the contributing factors of Lp-PLA2. RESULTS: Serum Lp-PLA2 level in
      the CP/HPL group and the CP group was significantly higher than in the healthy
      group. TC and TG levels in the CP/HPL group were higher than in the CP and
      control groups. No difference was observed for levels HDL-c and LDL-c and WBC
      counts among the groups. Linear regression analysis showed that the serum level
      of Lp-PLA2 was positively associated with bleeding on probing and WBC counts.
      CONCLUSION: Elevated level of Lp-PLA2 is associated with periodontal
      inflammation, indicating that periodontal treatment could reduce the risk of
      cardiovascular disease in CP subjects with hyperlipidaemia.

PMID- 22866280
TI  - Translucency of flowable bulk-filling composites of various thicknesses.
AB  - OBJECTIVE: To evaluate the translucency characteristics of new flowable bulk
      filling resin composites at various thicknesses. Experimental short fibre
      reinforced composite was also tested. METHODS: Two new brands of flowable bulk
      composites (Venus Bulk Fill and SureFil SDR Flow), experimental short fibre
      reinforced resin composite (FC) and, as control, conventional flow (Filtek
      Supreme Flow XT A3) and universal (Filtek Universal Supreme XTE A3B) resin
      composites were investigated. Translucency parameter was calculated for various
      thicknesses of composite (1, 2, 3, 4, 5 and 6 mm) over white and black
      backgrounds using spectrophotometry to determine the CIELAB values of each
      specimen. Data were statistically analysed with analysis of variance. RESULTS:
      Translucency values significantly correlated with thickness of resin composite
      specimens (P < 0.05). For the new types of flowable bulk-filling material,
      translucency was observed for thicknesses up to 5 to 6 mm, whereas for
      experimental FC composite, the effect was observed up to 4 to 5 mm, and for
      control flow and universal filling composites, up to 2 to 3 mm. CONCLUSION: New
      flowable bulk-filling resin composites have less masking ability than
      conventional universal filling resin composite materials, which should be taken
      into account when optimum colour match and aesthetic results are to be achieved.

PMID- 22866281
TI  - Effect of dehydration time on tooth colour measurement in vitro.
AB  - OBJECTIVE: To investigate the effect of dehydration time on tooth colour
      measurement in vitro using colourimetry. METHODS: Ten extracted human maxillary
      central incisors were used. L*a*b* values at the centre of the labial surface of
      each tooth were measured using a colourimeter. The first measurement was
      performed after removal of excess water. The second and third measurements were
      performed after the teeth had dried at room temperature for 2 h and 4 h,
      respectively. The colour differences (DeltaE) between dehydration time points
      were calculated. Repeated oneway ANOVA was performed for colour values at
      different dehydration time points. Pairwise comparison of group means (Student t
      test) was used to examine the differences between DeltaE and 1.5DeltaE (alpha =
      0.05). RESULTS: There were statistically significant changes in the L* values
      after 2 h and 4 h dehydration as well as between each DeltaE and 1.5DeltaE.
      Neither 2 h nor 4h dehydration resulted in change of a* value or b* value.
      CONCLUSION: Dehydration time affected colour measurement using a colourimeter;
      the teeth become lighter after dehydration for 2 h or longer.

PMID- 22866282
TI  - Effect of nanofiller on wear resistance and surface roughness of resin
      composites.
AB  - OBJECTIVE: To compare the wear resistance and surface roughness of nanofiller
      containing composites and microhybrid composites after simulated wear. METHODS:
      Five microhybrid composites and five nanofiller-containing resin composites were
      included in the study. Six cylindrical specimens with a diameter of 10 mm and a
      thickness of 6 mm for each material were prepared. The volume loss, vertical loss
      and the surface roughness (Ra) were determined after 800 cycles of simulated
      chewing motion. One specimen of each material was analysed by scanning electron
      microscopy (SEM) to compare the morphology of the wear surfaces. The microhybrid
      composites group and nanofiller-containing composites group were tested using the
      Mann-Whitney U test with a significance level of alpha = 0.05. RESULTS: For all
      microhybrid composites, the average wear volume loss and vertical loss were 56.44
      mm3 and 730.6 um, respectively, while the average wear losses of nanofiller
      containing composites were 40.15 mm3 and 528.17 um, respectively. The nanofiller
      containing composite GNH400N showed the least roughness (Ra = 0.346 +/- 0.076
      um), while the conventional microhybrid composite Ceramage showed the highest
      roughness (Ra = 0.699 +/- 0.214 um). However, wear resistance and surface
      roughness for the two groups showed no statistical difference. SEM micrographs of
      the nanofiller-containing composites after wear testing showed smoother and more
      uniform wear surfaces than for the microhybrid composites. CONCLUSION:
      Nanofillers did not significantly influence the wear resistance of resin
      composites, but might improve the surface roughness of resin composites.

PMID- 22866283
TI  - Anti-gingivitis effects of Acacia arabica-containing toothpaste.
AB  - OBJECTIVE: To evaluate the anti-plaque and anti-gingivitis properties of Acacia
      arabicacontaining toothpaste in an adult population. METHODS: Sixty subjects with
      gingivitis were randomly assigned to a test group (Acacia arabica-containing
      toothpaste) or control group (regular toothpaste). An analysis of plaque index
      (PI), gingival index (GI) and bleeding on probing index (BOP%) were carried out
      at baseline and after 28 days followed by a washout period. After the washout
      period, the test and control groups were crossed over and the assessments were
      repeated. RESULTS: Reductions in PI, GI and BOP% were observed in the test group
      compared with the control group. CONCLUSION: Brushing with Acacia arabica
      containing toothpaste may help inhibit gingivitis. It can be recommended for
      daily oral hygiene procedures.

PMID- 22866284
TI  - Nodular fasciitis in the orofacial region: a report of three cases.
AB  - Nodular fasciitis is a benign fibroblastic proliferate lesion that is thought to
      be a response of tissue to injury. It usually presents as a rapidly growing
      subcutaneous mass. Upper extremities are most commonly affected, followed by the
      head and neck region. The clinical behaviour and histological presentation mimic
      those of malignant tumours, thus the lesion is easily misdiagnosed. The authors
      report here three cases of orofacial nodular fasciitis and review the literature
      focused on the diagnosis of the disease. Patient one had a history of trauma. The
      physical examination, radiographic features and findings in surgery were
      suggestive of a malignant tumour. The final diagnosis of nodular fasciitis was
      made through the immunohistochemical pathology. The other two patients had no
      history of trauma, but presented typical clinical and pathological features of
      nodular fasciitis. It is essential that dentists are aware of the distinctions
      between nodular fasciitis and malignant tumours in order to limit overtreatment
      and treatment-related morbidity.

PMID- 22866285
TI  - Treatment of generalised aggressive periodontitis: a 4-year follow-up case
      report.
AB  - Aggressive periodontitis comprises a group of rare, often severe, rapidly
      progressive forms of periodontitis mostly characterised by an early age of
      clinical manifestation and a distinctive tendency for cases to aggregate in
      families. This case report presents a 16-year-old female patient with clinical
      and radiographic evidence of severe attachment loss, whose mother was also a
      patient with severe periodontal destruction. The girl was diagnosed with
      generalised aggressive periodontitis and received full-mouth scaling and root
      planing, bone graft surgeries and guided tissue regeneration on intrabony defects
      mesial of the mandibular first molars. Microbiological and immunological tests
      were performed on five selected sites before and at 2 months after initial
      therapy. Clinical and radiographic findings reported up to 4 years
      postoperatively indicated good effects and stability of treatment outcome.

PMID- 22866287
TI  - Are dental x-rays associated with an increased risk of meningioma?

PMID- 22866288
TI  - Immediate versus early loading of 6.5 mm-long flapless-placed single implants: a
      4-year after loading report of a split-mouth randomised controlled trial.
AB  - PURPOSE: To evaluate the medium-term effectiveness of 6.5 mm-long flapless-placed
      single implants immediately or early loaded at 6 weeks. MATERIALS AND METHODS:
      Thirty patients received two single NanoTite external hex Biomet 3i implants
      each, which were then randomly allocated to be immediately or early loaded
      according to a splitmouth design. Implants had to be inserted with a minimum
      torque of >40 Ncm. Provisional crowns were put in slight occlusal contact and
      replaced by definitive crowns 3 months after loading. Patients were followed for
      4 years after loading. Outcome measures were implant failures, biological and
      biomechanical complications, peri-implant marginal bone level changes, and
      patient preference. RESULTS: Twenty-nine implants were immediately loaded and 31
      early loaded. Four years after loading, no drop-outs occurred. One implant failed
      in each group within 2 months after loading. Seven patients experienced
      complications at immediately loaded implants and 6 at early loaded implants.
      There were no statistically significant differences between groups for implant
      losses, complications, mean marginal bone level changes and patient preference.
      CONCLUSIONS: Flapless-placed 6.5 mm-long single implants can be immediately
      loaded and remain successful up to 4 years after loading. Even longer follow-ups
      are still needed to evaluate the longterm prognosis of short implants.

PMID- 22866289
TI  - Comparison of variable-thread tapered implant designs to a standard tapered
      implant design after immediate loading. A 3-year multicentre randomised
      controlled trial.
AB  - OBJECTIVES: This randomised, controlled multicentre trial aimed at comparing two
      versions of a variable-thread dental implant design to a standard tapered dental
      implant design in cases of immediate functional loading for 36 months after
      loading. MATERIALS AND METHODS: 177 patients (325 implants) were included at 12
      study centres and randomly allocated into one of three treatment groups: NAI
      (variable-thread design, NobelActive internal connection), NAE (variable-thread
      design, NobelActive external connection) and, as control, NR (standard tapered
      design, NobelReplace tapered groovy). Inclusion criteria concerned healed bony
      implant sites and feasibility for immediate loading. Clinical and radiographic
      examinations were performed at implant placement and after 3, 6, 12, 24 and 36
      months. The outcome measures were marginal bone remodelling (primary outcome),
      implant survival and success, papilla score, plaque accumulation, and bleeding on
      probing. RESULTS: 127 patients (NAI: 45, NAE: 41, NR: 41) were followed-up and
      evaluated after 36 months. No significant differences in cumulative survival
      rates were seen for the groups (NAI: 95.7%; NAE: 96.3%; NR: 96.6%). In all
      groups, bone remodelling occurred during the first 3 months, with stable or even
      increasing bone levels after the initial remodelling period. The bone remodelling
      from insertion to 36 months for the NAI group (-0.89 +/- 1.65 mm) was comparable
      (P = 0.98) to that of the NR group (-0.85 +/- 1.32 mm). The NAE group showed
      comparable bone remodelling during the first year, with an increase in following
      years resulting in significantly less overall bone loss (-0.16 +/- 1.06 mm) (P =
      0.041). Overall improvement in papilla size was observed in all treatment groups.
      CONCLUSIONS: Over 36 months, the results show stable or improving bone levels for
      all treatment groups after the initial bone remodelling seen during the first 3
      months after placement. The variable- thread implants showed results comparable
      to those of standard tapered implants in cases of immediate function, and
      therefore can be considered as a treatment option for immediate loading.

PMID- 22866290
TI  - The comparison of two techniques to increase the amount of peri-implant attached
      mucosa: free gingival grafts versus vestibuloplasty. One-year results from a
      randomised controlled trial.
AB  - AIMS: The objective of this randomised controlled trial was to compare the
      efficacy of two techniques for increasing the amount of keratinised mucosa around
      implants: free gingival grafts versus classic vestibuloplasty. MATERIALS AND
      METHODS: Sixty-four patients with 64 implants presenting keratinised mucosa <1.5
      mm and showing signs of peri-implant mucositis were randomly assigned to two
      groups. Thirty-two implants received free gingival grafts (FGG group) while 32
      implants were treated via vestibuloplasty (VP group). Plaque Index (PI), Gingival
      Index (GI), probing depth (PD) and the width of attached mucosa (WAM) were
      measured at baseline and 1, 3, 6 and 12 months following surgery. RESULTS: WAM in
      the FGG group was significantly greater than the VP group at 3, 6 and 12 months
      (P = 0.000). In the FGG group, the final gain in WAM was greater (2.36 mm in FGG
      group, 1.15 mm in VP group) (P = 0.000) and the postoperative relapse was smaller
      (2.00 mm in FGG group, 3.06 mm in VP group) (P = 0.000). The VP group had higher
      PD values at 3, 6 and 12 months (P = 0.02, P = 0.024, P = 0.000, respectively).
      CONCLUSIONS: The application of FGG is a more predictable method for enhancing
      the width of attached mucosa in the vicinity of implants compared with classic
      vestibuloplasty.

PMID- 22866291
TI  - Posterior atrophic jaws rehabilitated with prostheses supported by 5 x 5 mm
      implants with a novel nanostructured calcium-incorporated titanium surface or by
      longer implants in augmented bone. Preliminary results from a randomised
      controlled trial.
AB  - PURPOSE: To evaluate whether 5 * 5 mm dental implants with a novel nanostructured
      calcium-incorporated titanium surface could be an alternative to at least 5 * 10
      mm-long implants placed in bone augmented with bone substitutes in posterior
      atrophic jaws. MATERIALS AND METHODS: Forty patients with atrophic posterior
      (premolar and molar areas) mandibles having 5 to 7 mm of bone height above the
      mandibular canal and 40 patients with atrophic maxillae having 4 to 6 mm below
      the maxillary sinus, were randomised according to a parallel group design to
      receive one to three 5 * 5 mm implants or one to three at least 5 * 10 mm-long
      implants in augmented bone at two centres. Mandibles were vertically augmented
      with interpositional bovine bone blocks and resorbable barriers and implants were
      placed after 4 months. Maxillary sinuses were augmented with particulated porcine
      bone via a lateral window covered with resorbable barriers and implants were
      placed simultaneously. All implants were submerged and loaded after 4 months with
      provisional prostheses. Four months later, definitive screw-retained or
      provisionally cemented metal-ceramic or zirconia prostheses were delivered.
      Outcome measures were prosthesis and implant failures as well as any
      complication. RESULTS: Patients were followed to 4 months post-loading with the
      exception of one patient who underwent mandibular augmentation and had multiple
      complications at and after grafting, and subsequent graft failure, who did not
      want to go ahead with the treatment. This case was considered a complete failure.
      There were no statistically significant differences in prosthesis and implant
      failures. In mandibles, apart from the complete graft failure, one 5 * 10 mm
      implant failed at placement of the provisional prosthesis. In maxillae, one 5 * 5
      mm implant failed with its provisional crown 3 months after loading. All
      complications occurred before loading. Significantly more intra- and
      postoperative complications occurred at both mandibular and maxillary grafted
      sites: 16 augmented patients were affected by complications versus 8 patients
      treated with short implants in the mandible (P = 0.022; difference in proportion
      = 0.40; CI 95% 0.12 to 0.68), and 5 sinus-lifted patients versus none treated
      with maxillary short implants (P = 0.047; difference in proportion = 0.25; CI 95%
      0.06 to 0.44). CONCLUSIONS: Short-term data (4 months after loading) indicate
      that 5 * 5 mm implants achieved similar results compared to longer implants
      placed in augmented bone. Short implants might be a preferable choice to bone
      augmentation especially in posterior mandibles since the treatment is faster,
      cheaper and associated with less morbidity. However, 5 to 10 years of post
      loading data are necessary before making reliable recommendations.

PMID- 22866292
TI  - Efficacy of quick-release lornoxicam versus placebo for acute pain management
      after dental implant surgery: a randomised placebo-controlled triple-blind trial.
AB  - AIM: To assess the efficacy of quick-release lornoxicam (LNX) on patient-reported
      acute pain after dental implant surgery. MATERIALS AND METHODS: The study
      included subjects in good general health, aged 18 to 65 and scheduled to receive
      a maximum of three implants in the same quadrant. Participants received either 8
      mg LNX or placebo and were asked to use the medications in case of pain in the
      first 120 min after implant surgery. Assessment of efficacy was performed using
      self-assessment questionnaires for the evaluation of pain intensity and pain
      relief for 12 h post dosing. Patients were also asked to record the rescue
      analgesic number. Evaluation of patient satisfaction was assessed using a 7-point
      scale. Safety was evaluated by the incidence of adverse events. RESULTS: A total
      of 83 (LNX/placebo, 42/41) patients who met the inclusion criteria and finished
      the evaluation period were included in the study. The proportion of patients
      experiencing postoperative pain was significantly lower in the LNX-treated group
      compared to the placebo group. Patients in the LNX group reported significantly
      higher pain relief scores than the placebo group. Twenty-nine patients in the
      placebo group and 6 patients in the LNX group used rescue analgesics. The number
      of used rescue analgesics was 1.024 +/- 0.79 and 0.167 +/- 0.43 in the placebo
      and LNX groups, respectively. The level of patient satisfaction was significantly
      higher in the LNX-treated patients (P = 0.007). No adverse events were reported
      during the study period. CONCLUSIONS: Quick-release LNX is effective in
      postoperative acute pain control and has a high safety profile following dental
      implant surgery.

PMID- 22866293
TI  - Brain plasticity and cortical correlates of osseoperception revealed by punctate
      mechanical stimulation of osseointegrated oral implants during fMRI.
AB  - PURPOSE: Our aim was to unveil the cortical neural correlates of osseoperception,
      i.e. the tactile sensation perceived when loading a bone-anchored implant, by
      taking oral implants as a model. This was performed in a cross-sectional
      observational study with 9 volunteering patients and 10 age-matched controls. For
      each patient, functional magnetic resonance imaging (fRMI) recordings were made
      during punctate mechanical stimulation of either teeth or osseointegrated
      implants in the maxillary incisor area. MATERIALS AND METHODS: During fMRI
      recordings, 1 Hz punctate tactile stimuli were applied either on a maxillary left
      central incisor, canine tooth or central incisor implant. A block design paradigm
      was used to stimulate, in 9 patients, maxillary left central incisor implants
      (I21-p) and maxillary left canines (T23-p). In 10 control subjects, maxillary
      left central incisors and canines (T21-c, T23-c) were stimulated. Random effect
      group analyses were performed for each stimulated site, and differences in
      cortical activity elicited when loading teeth or implants were examined using
      ANOVA. RESULTS: As a group, patients activated somatosensory area S2 bilaterally
      for both I21 and T23, while controls activated S1 and S2 bilaterally for T21 and
      T23. At an individual level, S1 was activated by 4/9 implants, mainly on the
      ipsilateral side. The stimulated implants activated a larger bilateral cortical
      network outside the somatosensory areas: in parietal, frontal and insular lobes,
      the main clusters being located in the inferior frontal gyri. Stimulation of T23
      in patients resulted in an activation pattern intermediate between that of the
      implants and that of natural teeth. CONCLUSION: This study demonstrates that
      punctate mechanical stimulation of oral implants activates both primary and
      secondary cortical somatosensory areas. It also suggests that brain plasticity
      occurs when extracted teeth are replaced by endosseous implants. This cortical
      activation may represent the underlying mechanism of osseoperception.

PMID- 22866294
TI  - Tripeptide Pro-Gly-Pro prevents disturbances in osmotic resistance of rat
      erythrocytes under conditions of inflammation.
AB  - The development of inflammation (experimental model of peritonitis induced by
      administration of sodium thioglycolate) was accompanied by a decrease in osmotic
      resistance of erythrocytes. Changes in osmotic resistance of erythrocytes
      associated with preliminary (15 min before induction of inflammation)
      administration of peptide Pro-Gly-Pro were significantly weaker, and the
      percentage of hemolyzed cells was reduced. The peptide injected against the
      background of developed inflammation (1 h 45 min after induction) had no
      corrective effect on osmotic resistance. During in vitro experiments, Pro-Gly-Pro
      did not affect hemolysis of intact erythrocytes. These results support the
      assumption that prophylactic administration of the peptide protects erythrocyte
      membranes and increases their osmotic resistance.

PMID- 22866295
TI  - Binary mechanism of action of cognition enhancer NT1505 on glutamate receptors.
AB  - Compound NT1505 potentiates AMPA receptors in rat brain neurons and
      simultaneously noncompetitively blocks NMDA receptors via two different
      mechanisms. Considering previously obtained data on strong cognition-enhancing
      properties of this compound we can conclude that NT1505 is a novel cognition
      stimulator exhibiting properties of a positive modulator of AMPA receptors and a
      blocker NMDA receptor.

PMID- 22866296
TI  - Elucidation of the mechanisms of membranotropic effects of RU-1203 on ionic
      channels of Lymnaea stagnalis neurons.
AB  - RU-1203-induced norBNI-irreversible inhibition of sodium (INa), calcium (ICa),
      and slow and fast potassium currents (IKs and IKf) was demonstrated in isolated
      neurons of Lymnaea stagnalis.

PMID- 22866297
TI  - Emotional stress in rats changes concentration and composition of extracellular
      DNA circulating in blood plasma under normal conditions and in cerebral ischemia.
AB  - We studied quantitative and qualitative characteristics of extracellular DNA
      circulating in the blood plasma of Wistar rats under normal conditions, in
      psychoemotional stress (after 18 hours of aggressive conflict situation), and in
      acute cerebral ischemia. It was found that animals predisposed to psychoemotional
      stress normally have increased levels of antibodies against low excreted fragment
      of transcribed region of ribosomal DNA repeat rich in cytosine-guanine (CpG). A
      sharp increase in the level of circulating extracellular DNA was noted. Its
      increase was more pronounced during ischemia against the background of
      psychoemotional stress than in the control. These data suggest that multiple
      stress exposures experienced during the life can result in accumulation of GpG
      rich sequences in the plasma of individuals predisposed to psychoemotional
      stress.

PMID- 22866298
TI  - Hemostatic system in Wistar rats in different types of oxidative stress.
AB  - We studied parameters of hemostatic homeostasis in isolated and combined exposure
      to low-intensity gamma-irradiation in a low dose, hyperbaric oxygenation, and
      antiorthostatic hypokinesia. Complex effects of the above stress factors are
      accompanied by a pronounced hypercoagulable shift with signs of thrombinemia
      against the background of depressed fibrinolysis, which indicates the risk of
      intravascular blood coagulation.

PMID- 22866299
TI  - Cardioprotective effect of ischemic postconditioning on the model of isolated
      heart.
AB  - Irreversible cardiomyocyte damage was induced by 45-min global ischemia followed
      by 30-min reperfusion in Langendorff-perfused isolated rat heart. Cell damage was
      assessed by the release of creatine phosphokinase into the perfusate. The hearts
      were subjected to the following postconditioning protocols: 1) three cycles of 10
      sec reperfusion and 10-sec ischemia, total cycle time 20 sec; 2) six cycles of 10
      sec reperfusion and 10-sec ischemia, total cycle time 20 sec; 3) three sessions
      of 20-sec reperfusion and 20-sec ischemia, total cycle time 40 sec; 4) 6 cycles
      of 20-sec reperfusion and 20-sec ischemia, total cycle time 40 sec; 5) 3 cycles
      of 30-sec reperfusion and 30-sec ischemia, total cycle time 60 sec. It was found
      that only postconditioning with a total cycle time of 40 sec or 60 sec prevents
      myocardial reperfusion injury.

PMID- 22866300
TI  - Influence of 5-HT(2) receptor agonist on cardiac pumping function of trained
      offspring of trained rats.
AB  - We studied cardiac pumping function in the offspring of rats subjected to
      swimming exercise and the offspring of untrained rats. The rat pups were adapted
      for swimming with stepwise increasing load from day 21 to 70 life. At the age of
      21 and 70 days, offspring of trained rats showed lower HR and significantly
      higher stroke volume and cardiac output than offspring of untrained rats. Agonist
      of 5-HT(2)-receptors alpha-methyl-5-hydroxytryptamine maleate (30 MUg/kg) reduced
      enhanced stroke volume in trained offspring born by trained mothers. In trained
      offspring of untrained rats, the agonist had more pronounced effect on HR.

PMID- 22866301
TI  - Cytokine-secreting activity of blood eosinophils in pulmonary tuberculosis.
AB  - Modern immunological studies showed that eosinophilic granulocytes producing the
      key mediators of cellular and humoral immune response contribute to the common
      cytokine imbalance developing in tuberculous infection. A significant increase in
      BCG-induced secretion of IL-2, IL-5, and TNF-alpha by eosinophils in patients
      with pulmonary tuberculosis indicated high reserve reactivity of eosinophilic
      cells realizing their functional potential in regulation of the specific
      resistance reactions of the microorganism under conditions of M. tuberculosis
      infection.

PMID- 22866302
TI  - Effects of fatty acids on human serum albumin binding centers.
AB  - Albumin is a carrier of nonesterified long-chain fatty acids and many other
      ligands. The status of its binding centers was studied for various proportions of
      nonesterified long-chain fatty acids and albumin as exemplified by palmitic acid.
      The status of the binding center was tested by recording K-35 probe fluorescence
      decay in the subnanosecond band. This method showed the work of three types of
      centers. Palmitic acid enhanced binding activity of all centers, though to a
      different degree: if the palmitic acid/albumin proportion increased to 2-3, the
      probe binding to type 1 centers (located in the drug center I region) increased
      1.5 times, while binding to type 3 centers increased more than 3-fold.
      Modification of these centers by nonesterified long-chain fatty acids was similar
      in the isolated human albumin preparation and in diluted blood serum. Hence, K-35
      probe showed the actual status of various albumin centers, their binding capacity
      depending to a different measure on the fatty acid charge of albumin.

PMID- 22866303
TI  - Anticoagulant, fibrinolytic, and hypoglycemic effects of tetrapeptide Arg-Pro-Gly
      Pro.
AB  - It was found that 3-fold intranasal administration of Arg-Pro-Gly-Pro peptide in
      a dose of 1 mg/kg body weight under conditions of experimental persistent
      hyperglycemia prevents the development of diabetes in experimental rats and
      produces normoglycemic, anticoagulant, fibrinolytic, and antiplatelet effects.

PMID- 22866304
TI  - Oxidation and endothelial dysfunction biomarkers of atherosclerotic plaque
      instability. Studies of the vascular wall and blood.
AB  - The concentrations of LPO products (including those present in LDL), oxidative
      modification of proteins, paraoxonase activity, concentrations of antioxidants,
      lipid values and biomarkers of endothelial dysfunction were studied in the blood
      and coronary artery intima/media of male patients with coronary atherosclerosis
      without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and
      lipoprotein (a) were higher, while the content of NO metabolites, sVCAM
      endothelial adhesion molecules, and LDL oxidation resistance were lower in men
      with mainly unstable atherosclerotic plaques in the coronary arteries in
      comparison with men with mainly stable plaques in the coronary arteries. Of these
      blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated
      with the presence of unstable atherosclerotic plaques. A significant correlation
      between the levels of biomarkers in the vascular wall and blood was detected only
      for LPO parameters.

PMID- 22866305
TI  - Antihypoxic and antioxidant effects of exogenous succinic acid and aminothiol
      succinate-containing antihypoxants.
AB  - Pronounced antihypoxic and antioxidant effects of preventive injection of
      succinic acid, aminothiol antihypoxants gutimine and amtizol, and succinate
      containing aminothiol antihypoxants gutimine succinate and amtizol succinate to
      Wistar rats with acute hypoxic hypoxia have been demonstrated. Exogenous succinic
      acid was inferior to aminothiol compounds by antihypoxic effect, but superior to
      them by its effect on the level of LPO products. Succinate in the aminothiol
      molecule modulated the intensity of their antihypoxic and antioxidant effects. It
      did not modulate the antihypoxic activity of amtizol, but reduced the antihypoxic
      effect of gutimine, presumably because of the physicochemical characteristics of
      aminothiols. Comparison of the intensities of antihypoxic and antioxidant effects
      of the studied drugs showed no direct relationship between these effects.

PMID- 22866306
TI  - Gender differences in pulmonary and immune response in acute experimental
      endotoxicosis.
AB  - Differences in the immune and inflammatory response were revealed in the lungs of
      male and female Wistar rats on day 1 after administration of LPS in a dose
      inducing the development of acute bacterial endotoxemia. Females showed more
      pronounced morphofunctional signs of immune system activation than males: this
      was characterized by more severe accidental involution of the thymus, devastation
      of the splenic white pulp, and enhanced production of IL-4, IL-12, and TNF-alpha
      by splenocytes. In males, production of the above cytokines decreased and
      inflammation in the lungs was more pronounced at these terms.

PMID- 22866307
TI  - Dynamics of structural transformations of BCG granulomas and expression of TNF
      alpha and granulocyte-macrophage CSF by macrophages in vitro.
AB  - The spleens were isolated from mice at different times after BCG infection and
      BCG granulomas were explanted and cultured in vitro. Cell migration,
      chemoattractant potential, and expression of TNF-alpha and granulocyte-macrophage
      CSF (GM-CSF) by macrophages migrated from granulomas were evaluated in
      granulomas. The number of macrophages able to migrate; migrating out of
      granulomas, expressing TNF-alpha and GM-CSF decreased with increasing the time
      after infection. The number of cells in "dissociating" granulomas correlates with
      the number of macrophages containing live BCG mycobacteria in the cytoplasm.

PMID- 22866308
TI  - Immunocytochemical study of Helicobacter pylori in the mucosae of the gastric
      antrum and rectum.
AB  - We present the results of bacterioscopic and immunocytochemical study of
      Helicobacter pylori in biopsy specimens from the gastric antrum and smears from
      the rectum. Predominance of spiral-shaped vegetative form of Helicobacter pylori
      in the antrum and the presence of cocci with Helicobacter pylori antigens in
      smears from the rectum were demonstrated in patients infected with Helicobacter
      pylori. The diagnostic sensitivity of non-invasive immunocytochemical
      Helicobacter pylori test in rectal smears was 90%, specificity 76%, and
      efficiency of the test 84%.

PMID- 22866309
TI  - Sexual dimorphism of mast cells in red bone marrow in normal rats and rats
      treated with preparation endorfain.
AB  - We studied immunological effects of Endorfain preparation. Daily oral
      administration of the preparation stimulated the immune system increasing
      migration and proliferation and accelerating differentiation of mast cells in the
      red bone marrow of rats with the pronounced sexual dimorphism.

PMID- 22866310
TI  - Effect of basal hormone profile on the formation of the vaginal bacterial cenosis
      in women.
AB  - Adhesion activity of L. acidophilus NK1, L. fermentum 90 TS4, and C. albicans 506
      B on female vaginal epithelium was studied. Adhesion of various lactobacillus
      species was hormone-dependent. Adhesion of C. albicans 506 B was not associated
      with estrogen level. The effects of synthetic drugs and phytopreparations used
      for hormone replacement on adhesion of vaginal microbiocenosis members varied.

PMID- 22866311
TI  - Effect of chronic emotional and pain stress on histone H3 phosphorylation in the
      hippocampus of rat strains with different excitability of the nervous system.
AB  - Long-term effects of chronic emotional and pain stress on histone H3
      phosphorylation by serine 10 in hippocampal CA3 neurons were examined 24 h, 2
      weeks, and 2 months after termination of the stress procedure in 2 rat strains
      differing by excitability of the nervous system. The low excitable rats with high
      threshold (HT) of excitability were characterized by a high baseline level of
      histone H3 phosphorylation in comparison with the high excitable rats with low
      threshold (LT) of excitability. The long-term emotional and pain stress
      significantly changed the number of positive immune cells in highly excitable
      rats: this parameter increased in 24 h and 2 weeks after the stress, but returned
      to the control level in 2 months. In contrast, stress did not affect histone H3
      phosphorylation in low excitable rats. Thus, long-term (up to 2 weeks) changes in
      histone H3 phosphorylation were reveled in rat hippocampal CA3 neurons, which
      depended on genetically determined functional status of the nervous system.

PMID- 22866312
TI  - Effect of anthralin on cell viability in human prostate adenocarcinoma.
AB  - The study revealed the key role of serine protease hepsin activity in transition
      of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of
      hepsin activity suppresses the invasive growth of the tumor. Hepsin is an
      convenient target for pharmacological agents, so the study of its inhibitory
      mechanisms is a promising avenue in drug development. Assay of proteolytic
      activity in various tumor cell lines in vitro showed that this activity in
      prostate adenocarcinoma cells significantly surpasses proteolytic activity in
      other examined tumor cell lines. Selective cytotoxic action of anthralin, an
      inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in
      comparison with other tumor cell lines.

PMID- 22866313
TI  - Changes in the levels of N-cadherin and PCNA in skin melanoma cells are mediated
      through matrix metalloproteinase 9.
AB  - Immunohistochemical studies revealed increased level of matrix metalloproteinase
      9 in skin melanoma cells. Inhibition of matrix metalloproteinase 9 with
      interfering RNA changed the level of PCNA and reduced N-cadherin content in
      melanoma cells. This attests to the involvement of matrix metalloproteinase 9 in
      the realization of invasion and metastatic growth and in the regulation of tumor
      growth and progress.

PMID- 22866314
TI  - Relationship of epidermal melanocytes and langerhans cells with epidermal cambial
      cells.
AB  - Studies of mouse ear epidermis showed that proliferative activity of basal
      epidermal cells has two active and two passive phases throughout 24 h. Active
      phases consist of two subphases: long (proliferation of cambial cell descendants)
      and very short (cambial cell proliferation). Cambial cells proliferate at the
      boundary between active and passive phases; this results in an increase in the
      counts of epidermal melanocytes and Langerhans cells resultant from division of
      epidermal cambial cells. The count of Langerhans cells almost 2-fold surpasses
      melanocyte count, because melanocytes gradually transform into epidermal basal
      cells.

PMID- 22866315
TI  - Effect of delta sleep-inducing peptide on oxidative modification of proteins in
      rat tissues and blood during physiological aging.
AB  - Accumulation of oxidized proteins (evaluated by the levels of carbonyl and SH
      groups) in tissues of 2-24-month-old rats
      (spleen>myocardium>testicles>liver>skeletal muscles) has been demonstrated.
      Exogenous delta sleep-inducing peptide injected subcutaneously to rats of
      different age in a dose of 100 MUg/kg by monthly 5-day courses protected proteins
      of the studied tissues from oxidation; its effect was tissue-specific. Delta
      sleep-inducing peptide exhibited a hypoglycemic effect: it prevented nonenzymatic
      glycosylation of hemoglobin and reduced the level of defective protein molecules
      during aging.

PMID- 22866316
TI  - Systemic markers of age-related changes in the lens.
AB  - A dependency was found between total protein content and cataract maturity (P=
      0.91, p<0.01). LPO intensity sharply increased and remained stably high after
      appearance of lens opacity. A strict negative correlation was found between the
      content of polyunsaturated fatty acids in earwax and lens nucleus (P=-0.7,
      p<0.01). The content of conjugated dienes, crotonic aldehyde, and Schiff bases
      decreased during cataract development. The content of vitamins B(2), A, and E
      decreased with increasing brown coloration of lens nucleus. Studying the
      parameters of lipid metabolism in wax-producing glands of the external ear canal
      we can evaluate the disturbances in lipid metabolism in the lens, which was
      confirmed by the correlation between fatty acid composition of the earwax and
      lens nucleus. These data do not demonstrate the dependence of the lens state on
      earwax, but suggest general features of the process in organs and tissues during
      aging. Some markers in the blood of patients with cataract change during progress
      of lens opacity and intensification of brown coloration of lens nucleus, but
      these changes are inspecific and reflect general activation of peroxidation
      processes and antioxidant system.

PMID- 22866317
TI  - Development of laboratory rats receiving silver-enriched ration for a long time.
AB  - We studied the effect of silver ions on the status and metabolism of copper in
      rats receiving Ag-diet from the first day of life and for 6 months. The effect of
      silver ions on copper metabolism was assessed by body weight, relative weight of
      organs (body weight/organ weight), oxidase activity, content of immunoreactive
      ceruloplasmin and copper concentration in blood serum, by the expression of
      copper-transporting protein genes in the liver, and copper and silver
      distribution in liver and brain cells. Brain functions were evaluated by open
      field behavior and passive avoidance conditioning. No acute deficiency of
      ceruloplasmin-associated copper was observed in rats receiving silver-enriched
      diet starting from the early postnatal period; copper metabolism in the liver did
      not change, psychoemotional state and memory corresponded to the control.
      However, Ag-diet almost 2-fold decelerated the growth of experimental rats. We
      hypothesize the existence of an unknown mechanism of copper delivery to organs in
      rats that is activated during the early ontogeny under conditions of
      ceruloplasmin-associated copper deficiency.

PMID- 22866318
TI  - Tissue reaction to a titanium-nickelide mesh implant after plasty of
      postresection defects of anatomic structures of the chest.
AB  - We studied morphological features of the regenerate formed after postresection
      defect plasty of the pericardium, diaphragm, and thorax with a mesh implant made
      of nanostructural titanium-nickelide threads. The newly formed tissue grew
      through the implant with the formation of an integrated tissue regenerate
      ensuring anatomic and physiological restoration of this area.

PMID- 22866319
TI  - Morphology of placental villi and development of hemorrhages in very small
      preterm newborns.
AB  - We performed a comparative morphometric and immunohistochemical studies of the
      placentas collected in preterm labor after 27-33-week gestation. Predominating
      branched angiogenesis processes and more pronounced vascularization of the
      placental villi were found in the group of newborns with hemorrhagic
      complications. These changes were paralleled by high expression of VEGF in all
      villous structures.

PMID- 22866320
TI  - Structural and functional analysis of cerebral basin arteries in different
      periods of hypertension.
AB  - Structure of arteries of different diameter in early and late periods of
      hypertension caused by experimental coarctation of the aorta was studied by
      histological and morphometric methods. Blood pressure was measured directly via
      catheterization of the common carotid artery and used for evaluation of
      hemodynamic in the cerebral basin. It was shown that the late period of
      hypertension is characterized by dilatation of medium arteries and constriction
      and increase tone of small arteries and arterioles. Comparison of blood pressure
      parameters with the parameters of inner diameter and thickness of the tunica
      media attests to progressive decrease of permissible tensile strength and
      initiation of rapture of the wall of small arteries and arterioles during chronic
      hypertension.

PMID- 22866321
TI  - Simulation of nonalcoholic steatohepatitis in rats.
AB  - The new model of nonalcoholic steatohepatitis in rats is based on alimentary
      effects of hypercaloric diet including much cholesterol and beef fat. This model
      reproduces structural and functional disorders in the liver, including hepatocyte
      fatty degeneration, parenchymatous necrosis and fibrosis paralleled by
      dyslipidemia and is intended for studies of the mechanisms of formation,
      progress, and therapy of liver diseases of noninfectious origin.

PMID- 22866322
TI  - Information value of functional status of the stomatognathic system for postural
      balance regulation.
AB  - We performed cluster analysis of stabilometry data of 129 men and 122 women at
      the age of 20-60 years using the following 4 methods: European stabilometry
      variant, Romberg test (European variant), Romberg test (American variant), and
      Romberg test (American Universal variant). Results of factor analysis of primary
      data matrix obtained during the test "eye open-teeth clenched" attest to higher
      clinical significance of absolute stabilometry parameters in comparison with
      relative ones. The results of factor analysis revealed peculiarities of
      functional status of the stomatognathic system as the postural sensor and its
      effect on postural balance. The contribution of the functional status of the
      stomatognathic system into the postural balance is about 2%.

PMID- 22866323
TI  - Argocytes containing enzyme nanoparticles reduce toxic concentrations of arginine
      in the blood.
AB  - A method for incorporation of arginase nanoparticles into mouse erythrocytes has
      been developed and the possibility of reducing blood arginine concentration in
      animals with experimental hyperargininemia with arginase-loaded erythrocytes
      (argocytes) has been studied. Argocyte infusion to animals with hyperargininemia
      led to a rapid decrease in blood arginine concentration within 1 h and this
      effect of argocytes persisted for at least 4 h. This was paralleled by an
      increase in plasma concentrations of urea and ornithine. Hence, plasma arginine
      is hydrolyzed by arginase incorporated into argocytes; argocytes are functionally
      active and can serve as a defense system in pathological hyperargininemia, while
      the method developed by us can be regarded as a new nanobiotechnology for
      medicine and veterinary.

PMID- 22866324
TI  - Experimental development of new surgical suturing materials with complex
      biological activities.
AB  - New surgical suturing materials with complex biological activities (antibacterial
      and stimulating tissue regeneration) have been developed. In vitro studies
      demonstrated pronounced and prolonged (up to 10-12 days) antibacterial activity.
      Experiments on 108 male albino rats proved the positive effect of the materials
      on the wound process: shortening of the inflammation period, more rapid
      transformation of the granulation tissue, more rapid epithelialization of the
      wound and its pronounced contraction.

PMID- 22866325
TI  - Selective adsorption of 2,4-dinitrophenol on molecularly imprinted nanocomposites
      of mesoporous silica SBA-15/polyaniline.
AB  - Surface imprinting and adoption of a nano-sized physical form are two effective
      approaches to overcome the template transfer difficulty within molecularly
      imprinted polymers (MIPs). This work is an attempt to conquer the problem of
      template transfer difficulty within MIPs by using a nano-reactor as a substrate
      for the reaction between the monomer and the template. Negatively charged
      hexagonal nano-channels of SBA-15 can act as a support for attachment of
      positively charged aniline monomers and the 2,4-dinitrophenol (2,4-DNP) template.
      The imprinted and non-imprinted SBA-15/polyaniline nanocomposites were
      characterized by Fourier transform infrared (FT-IR), transmission electron
      microscopy (TEM), scanning electron microscopy (SEM) and nitrogen adsorption
      desorption isotherms. The results showed that the synthesized polymer possessed a
      highly ordered mesoporous structure. The distribution coefficient values of 2,4
      DNP, K(d (2,4-DNP)), were estimated as 301.4 +/- 2.3 and 101.2 +/- 1.0 mL g(-1)
      for imprinted and non-imprinted polymers (NIP), respectively. The MIP-solid-phase
      extraction (SPE) process was optimized by evaluating the type of washing solvent
      and the composition and volume of the eluting solvent. The prepared MIP was used
      as a selective sorbent for SPE of 2,4-DNP in the presence of phenolic compounds
      in tap and sea water. The experimental results indicated that the MIP-SPE and NIP
      SPE column yielded recoveries higher than 96% and 38%, respectively. The R.S.D.
      values were also lower than 3.2% and 4.6% for MIP-SPE and NIP-SPE, respectively.

PMID- 22866326
TI  - Highly selective fluorescence turn-on sensing of gold ions by a nanoparticle
      generation/C-I bond cleavage sequence.
AB  - We have developed a quickly responsive, and specific fluorescent assay for the
      detection of Au(III) on the basis of the formation of gold nanoparticles in the
      presence of HEPES, which cleave the C-I bond of I-BODIPY 1 to yield the highly
      fluorescent H-BODIPY 2.

PMID- 22866327
TI  - Ferrocene-based anion receptor bearing amide and triazolium donor groups.
AB  - A novel ferrocene-based anion receptor bearing amide and triazolium donor groups
      and its anion complexation have been reported. We found that it shows marked
      electrochemical selectivity to F(-), followed by AcO(-) > Cl(-) > Br(-) > I(-),
      which is in accordance with (1)H NMR titration results.

PMID- 22866328
TI  - Studies of the interaction of two organophosphonates with nanostructured silver
      surfaces.
AB  - Electrochemical cycling of silver surfaces in the presence of the
      organophosphonates paraoxon and malathion leads to changes in the electrochemical
      response of silver and the formation of silver nanostructures. Adsorption of the
      organophosphonates onto the silver surfaces causes a significant reduction in the
      observed current response due to an increase in the charge transfer resistance.
      Surface enhanced Raman spectroscopy (SERS) measurements indicate that paraoxon
      adsorbs with no structural changes, while malathion decomposes and a
      thiophosphonate interacts with the surface. The SERS study of these adsorbates
      was carried out by changing the electrochemical conditions and the concentration
      of the organophosphonates. The size of the nanostructures greatly influences the
      SERS signal and it is observed that the strongest enhancement is observed for mid
      sized nanostructures with a uniform thickness on the surface. The limit of
      detection was shown to be in the range of 10 nM to 10 pM for paraoxon and
      malathion, respectively.

PMID- 22866329
TI  - Ultrasensitive electrochemical immunosensor for CA 15-3 using thionine-nanoporous
      gold-graphene as a platform and horseradish peroxidase-encapsulated liposomes as
      signal amplification.
AB  - This paper describes a novel electrochemical immunosensor using a nanoporous gold
      (NPG)/graphene (GN) hybrid platform combined with horseradish peroxidase (HRP)
      encapsulated liposomes as labels for the sensitive detection of cancer antigen 15
      3 (CA 15-3). The electrochemical detection was based on the released HRP from HRP
      encapsulated liposomes toward the reduction of H(2)O(2) with the help of the
      thionine (TH) electron mediator. In the presence of CA 15-3, HRP@liposomes and TH
      NPG-GN formed a sandwich-type immunocomplex, and the immunocomplex increased with
      the increment of the CA 15-3 concentration in the sample. The more CA 15-3
      antigen in the sample there was, the more HRP@liposomes/anti-CA 15-3 in the
      immunocomplex there were. Thus, the catalytic current increased. Under optimized
      conditions, the linear range of the immunoassay is 2 * 10(-5) to 40 U mL(-1) with
      a detection limit of 5 * 10(-6) U mL(-1) CA 15-3. The CA 15-3 concentrations of
      the clinical serum specimens assayed by the developed immunoassay showed
      consistent results in comparison with those obtained by a commercially available
      electrochemiluminescence assay. This proposed immunoassay system had many
      desirable merits including sensitivity, accuracy, and minimal instrumentation
      required. Significantly, the new protocol may be quite promising, with
      potentially broad applications for clinical immunoassays.

PMID- 22866330
TI  - Thinking globally.

PMID- 22866332
TI  - [Consensus document on sleep apnea-hypopnea in children. Prologue].

PMID- 22866331
TI  - Xylose isomerase improves growth and ethanol production rates from biomass sugars
      for both Saccharomyces pastorianus and Saccharomyces cerevisiae.
AB  - The demand for biofuel ethanol made from clean, renewable nonfood sources is
      growing. Cellulosic biomass, such as switch grass (Panicum virgatum L.), is an
      alternative feedstock for ethanol production; however, cellulosic feedstock
      hydrolysates contain high levels of xylose, which needs to be converted to
      ethanol to meet economic feasibility. In this study, the effects of xylose
      isomerase on cell growth and ethanol production from biomass sugars
      representative of switch grass were investigated using low cell density cultures.
      The lager yeast species Saccharomyces pastorianus was grown with immobilized
      xylose isomerase in the fermentation step to determine the impact of the glucose
      and xylose concentrations on the ethanol production rates. Ethanol production
      rates were improved due to xylose isomerase; however, the positive effect was not
      due solely to the conversion of xylose to xylulose. Xylose isomerase also has
      glucose isomerase activity, so to better understand the impact of the xylose
      isomerase on S. pastorianus, growth and ethanol production were examined in
      cultures provided fructose as the sole carbon. It was observed that growth and
      ethanol production rates were higher for the fructose cultures with xylose
      isomerase even in the absence of xylose. To determine whether the positive
      effects of xylose isomerase extended to other yeast species, a side-by-side
      comparison of S. pastorianus and Saccharomyces cerevisiae was conducted. These
      comparisons demonstrated that the xylose isomerase increased ethanol productivity
      for both the yeast species by increasing the glucose consumption rate. These
      results suggest that xylose isomerase can contribute to improved ethanol
      productivity, even without significant xylose conversion.

PMID- 22866333
TI  - Expression of concern.

PMID- 22866335
TI  - Retraction notice to: The role of ubiquitination in hepcidin-independent and
      hepcidin-dependent degradation of ferroportin.

PMID- 22866334
TI  - Retraction notice to: Decoupling ferritin synthesis from free cytosolic iron
      results in ferritin secretion.

PMID- 22866336
TI  - Cells, shared memory and breaking the PTM code.

PMID- 22866337
TI  - Lateral epicondylitis: a review of the literature.
AB  - Lateral epicondylitis (Tennis Elbow) is the most frequent type of myotendinosis
      and can be responsible for substantial pain and loss of function of the affected
      limb. Muscular biomechanics characteristics and equipment are important in
      preventing the conditions. This article present on overview of the current
      knowledge on lateral Epicondylitis and focuses on Etiology, Diagnosis and
      treatment strategies, conservative treatment are discussed and recent surgical
      techniques are outlined. This information should assist health care practitioners
      who treat patients with this disorder.

PMID- 22866338
TI  - [Then, with enhanced confidence].

PMID- 22866339
TI  - Predictably unpredictable.

PMID- 22866340
TI  - Revitalizing the Health Belief Model in support of shared decision-making.

PMID- 22866341
TI  - [Mast cells and irritable bowel syndrome].

PMID- 22866342
TI  - [Clinical practice guideline on the diagnosis and treatment of pediatric acute
      infectious diarrhea in Peru - 2011].

PMID- 22866343
TI  - [VIII International Conference <" Systemic Circulation, Microcirculation And
      Haemorheology> (from angiogenesis to central circulation)].
AB  - From June 10th -14th, 2011, Yaroslavl played host to the traditional VIII
      International Conference <Systemic Circulation, Microcirculation and
      Haemorheology,> (from angiogenesis to central circulation) with a school for
      young scientists. The reports discussed cellular and molecular mechanisms of
      changes in the microrheological properties of RBCs and WBCs. as well as a role of
      a series of signal compounds and their receptors in regulation of
      angiogenesis.Also presented were the results of using new methods of
      investigations such as atomic-power microscopy, computer-assisted video
      biomicroscopy of vessels of bulbar conjunctiva, bioimpedance spectroscopy.Some
      works examined the effect of drugs and certain chemical compounds on
      microrheological properties of RBCs, as well as peculiarities of haemorheological
      indices in certain conditions:obesity, ischaemic heart disease on the background
      of arterial hypertension, myocardial infarction, in nephrological patients, in
      various types of stress, systemic lupus erythematosus, sickle-cell anaemia,
      chronic obstructive pulmonary disease.Some works were dedicated to acute
      impairments of cerebral circulation both in experimental and clinical
      conditions.A large aspect of the Conference's work touched upon physiological and
      pathophysiological mechanisms of alterations in the systemic circulation and
      microcirculation. A separate division of the Program was called ,Haemostasis,
      thromboses and haemorheology: points of interactions. There was also a master
      class: ,Study of molecular signalling pathways of erythrocytes associated with
      alteration in their microrheologicalproperties

PMID- 22866345
TI  - Thoughts on medical learning.

PMID- 22866344
TI  - [Endovasal obliteration of the main subcutaneous veins - a mechanism of action].
AB  - Active dissemination implementation of endovascular methods has during the past
      decade been a progressive tendency of the development of surgical treatment
      management of varicose disease.Amongst these methods, endovasal laser
      obliteration in Russia occupies the leading place. Despite widespread
      implementation of this method into clinical practice still there are neither
      common concepts on the mechanisms of action of laser energy, inducing lesions of
      the venous wall followed by obliteration, nor, consequently,criteria for
      administration thereof The search for an optimal method and mode of intravascular
      intervention is based on study-ing the mechanisms of the damaging action of laser
      energy on the venous wall. The article contains a literature review of the
      studies dedicated to investigating the mechanisms of action of endovasal methods
      of treatment for varicose disease.

PMID- 22866346
TI  - Long-term retention of information across the undergraduate medical school
      curriculum.
AB  - Medical school curricula must teach information to be mastered and retained for
      future clinical applicability. This study evaluated retention of knowledge across
      four years of medical education comparing two educational models. Clinical
      application and spaced learning may lead to better retention across all of
      medical school.

PMID- 22866347
TI  - Student understanding of type 2 diabetes mellitus.
AB  - BACKGROUND: An estimated 25.8 million people in the United States have type 2
      diabetes, including seven million people who have the disease but are
      undiagnosed. These numbers indicate that education about diabetes is needed.
      METHODS: To evaluate university students' knowledge about diabetes (risk factors,
      signs and symptoms and complications) we utilized a survey. Specifically, we
      determined: (1) knowledge of type 2 diabetes; (2) if participants' academic field
      of study affected their knowledge of type 2 diabetes; (3) if participants who had
      a family member with type 2 diabetes had a greater knowledge of the disease; and
      (4) if age affected students' knowledge of the disease. RESULTS: A questionnaire
      was completed by 469 students from The University of South Dakota. Students'
      knowledge of type 2 diabetes was poor: 30.1 percent of the students scored higher
      than 70 percent (with only 6.8 percent of the students scoring higher than 80
      percent). No significant differences in knowledge scores were found between
      students who pursued health-related fields of study versus students who did not.
      Participants who had a family member with type 2 diabetes had a greater knowledge
      of the disease and felt that they had a higher risk for getting the disease.
      Significant differences in knowledge were only found between the youngest and
      oldest age groups. CONCLUSIONS: USD students' knowledge of type 2 diabetes is
      limited. Solutions need to communicate the risk factors and severity of the
      disease. Possible ways for improving diabetes education is to include health
      fairs as well as to integrate diabetes modules into K-12 education courses.

PMID- 22866348
TI  - Adult immunizations: an update.

PMID- 22866349
TI  - National Quality Strategy: 2012 annual progress report.

PMID- 22866350
TI  - Fatherhood.

PMID- 22866351
TI  - Prescription for health cost reduction: an editorial.

PMID- 22866352
TI  - Osteoporosis in persons with HIV: a future epidemic?
AB  - Given the aging of the American population with human immunodeficiency virus
      (HIV) and the high prevalence of suboptimal 25(OH)D (vitamin D) levels,
      osteoporosis is likely to be a growing concern among clinicians caring for this
      population. HIV infection has been shown to be a strong predictor for an abnormal
      dual X-ray absorptionmetry testing and is potentially a risk for fractures at
      older ages. This paper reviews management issues for osteoporosis specific to the
      population with HIV, including both prevention and treatment strategies.

PMID- 22866353
TI  - The state of trauma care in Louisiana--impediments and opportunities: a survey of
      the state's surgeons.
AB  - Trauma is the leading cause of death in persons under 45 years of age. A looming
      physician shortage, comparatively high rates of injury in the state, and the high
      cost of caring for the injured has raised the question of how to best deal with
      this problem in Louisiana. A 37-question survey was sent to all 324 Louisiana
      members of the American College of Surgeons. The survey assessed characteristics
      of surgeons, the hospitals and their resources, and perceived impediments to
      trauma care. Seventy-three percent of responders provide trauma coverage to their
      hospitals. Ninety percent of hospitals have a blood bank; only 27.4% had 24-hour
      operating room availability. Most hospitals had adequate subspecialty
      availability. Major deterrents to trauma coverage that were identified were no
      control of schedule, no repayment for care, and interruption of a surgeon's
      elective schedule. Eighty-six percent of responders agreed the state should
      implement a statewide network. More than 90% said tertiary trauma centers should
      be in New Orleans, Shreveport, and Baton Rouge to provide trauma care. Louisiana
      has a surgical workforce trained and capable of trauma care. Impediments to
      surgeon involvement revolve upon reimbursement and interruption of elective
      practice. An organized trauma system will help triage critically ill patients to
      appropriate trauma centers for improved care by appropriate surgeons.

PMID- 22866354
TI  - Bilateral coronary cameral fistulae and coronary artery disease presenting in an
      elderly woman.

PMID- 22866355
TI  - Bilateral globus pallidus lesions.
AB  - Following a hypoxic-ischemic insult, the globus pallidus is selectively spared
      from ischemic injury in contrast to the caudate and putamen. The known causes for
      hemorrhagic and necrotic lesions selective for injuring the globus pallidus are
      varied but few. The most widely known etiology is in fatal cases of carbon
      monoxide poisoning. Additionally reported associations include fatalities
      involving 3,4-methylenedioxymethamphetamine; cocaine; opiates; and cyanide
      poisoning. These bilateral globus palladus necrotic lesions have been reported to
      occur in 5-10% of opiate addicts. In this article, we present a striking photo of
      selective symmetrical bilateral globus pallidus necrosis following cocaine and
      opiate abuse.

PMID- 22866356
TI  - Seasonal primary amebic meningoencephalitis (PAM) in the south: summertime is PAM
      time.
AB  - Primary amebic meningoencephalitis (PAM), a typically fatal, free-living amebic
      infection of the central nervous system (CNS), is caused by the thermophilic,
      freshwater protozoan, Naegleria fowleri. More than 145 cases of PAM have been
      reported worldwide, with most reported cases in the United States (US). Since
      annual PAM case clusters in the US and worldwide have demonstrated recent
      increases over background cases, the objectives of this investigation included
      (1) an epidemiological and statistical analysis of a 2007 cluster of six PAM
      cases in the southern US, nested in a retrospective review of 121 confirmed US
      cases of PAM over the period, 1937 to 2007; and (2) a statistical analysis of all
      existing demographic, temporal, and behavioral risk factors for PAM. Significant
      risk factors for PAM in the United States included male sex and warm recreational
      freshwater exposures in seasonal patterns (July - August) in southern tier
      states, including Louisiana. Although there have been a few recent survivors of
      PAM treated with combinations of intensive critical care, antifungals, and
      synergistic antibiotics, case fatality rates for PAM remain very high. PAM is
      best prevented by combinations of public health educational and behavioral
      modification strategies. Further investigations will be required to determine the
      significance of freshwater wakeboarding as a significant risk factor for PAM and
      to determine any dose-response effects of global warming on rising freshwater
      temperatures and the growth of aquatic Naegleria fowleri.

PMID- 22866357
TI  - Radiology case of the month: two adults with intermittent abdominal pain.
AB  - Though usually thought of as a pediatric entity, intussusception may occur in
      adults, which account for 5% of cases. Intussusception may result from a
      pathologic lead point facilitating the process or may occur with no such lead
      point. As opposed to idiopathic predominance in children, most adult
      intussusception involves a lead point. Generally, large bowel lead points are
      more likely to be malignant than small bowel lead points. Clinical presentations
      of intussusception may be nonspecific, thus radiologic evaluation plays an
      essential role in diagnosis. Findings at computerized tomography (CT) include a
      target or sausage-shaped mass with or without signs of bowel obstruction.
      Treatment is aimed at relieving any obstruction and identifying potential causes
      of the intussusception.

PMID- 22866358
TI  - A 23-year-old man with fever and malaise.
AB  - Acute infection with human immunodeficiency virus (HIV) is infrequently
      diagnosed, owing in large part to vague or non-specific symptoms. Among the most
      common of these symptoms are fever, fatigue, pharyngitis, lymphadenopathy,
      anorexia, arthralgia, myalgia, rash, and headache. Some patients seek no medical
      attention for such symptoms, and others recall no symptoms whatsoever. Physicians
      in all healthcare environments must maintain a high index of suspicion for HIV in
      the setting of these symptoms. For suspected acute infection, rapid serologic
      tests should be supplemented with assays of p24 antigen and/or HIV RNA viral
      load. We report here a case of acute HIV infection in a young man who presented
      with a negative rapid serologic test, as well as pancytopenia and transaminitis.
      We also review the epidemiology, transmission, diagnosis, and management of acute
      HIV infection.

PMID- 22866359
TI  - Perceptions regarding death and dying of individuals with chronic kidney disease.
AB  - This research explores perceptions regarding death and dying among people with
      chronic kidney disease. The methodology for the study was narrative inquiry
      informed by social constructivism. In-depth narrative interviews were conducted
      on two occasions with 14 participants. The participants included 10 men and 4
      women (mean age of 66) who were treated in a mid-size Canadian city. Four themes
      relating to death and dying emerged from the data: awareness of death as a
      consequence of kidney failure, close calls, contemplation of suicide and/or
      withdrawal from dialysis, and preparing for death while living life. From the
      findings, it appeared that participants were very aware of the risk of dying from
      their illness, experienced serious health crises, and planned for their deaths.
      They were comfortable in discussing death and dying and acknowledged withdrawal
      from dialysis as an option.

PMID- 22866360
TI  - Personal paths of fluid restriction in patients on hemodialysis.
AB  - The aim of this study was to explore the perspectives of patients on hemodialysis
      about their experience of fluid restriction. Qualitative interviews were
      conducted to grasp the patients' lived experience, and from a phenomenological
      analysis, several categories emerged that describe patients' understanding. Three
      themes in particular from patients' experiences are described and discussed
      because of their relevance for health professionals. These include (a) fluid
      restriction introduces the perception of individuals to see themselves as addicts
      who deal with a constant inner conflict, (b) the difficulty in finding the right
      boundaries between common sense and scientific knowledge about fluid restriction,
      and (c) the role of personal motivations and willingness in pursuit of
      compliance. Recognizing the force of personal meaning for individuals with renal
      disease will support health professionals to help patients in pursuing the regime
      of fluid restriction.

PMID- 22866361
TI  - Improving blood pressure control in end stage renal disease through a supportive
      educative nursing intervention.
AB  - Hypertension in patients on hemodialysis (HD) contributes significantly to their
      morbidity and mortality. This study examined whether a supportive nursing
      intervention incorporating monitoring, goal setting, and reinforcement can
      improve blood pressure (BP) control in a chronic HD population. A randomized
      controlled design was used and 118 participants were recruited from six HD units
      in the Detroit metro area. The intervention consisted of (1) BP education
      sessions; (2) a 12-week intervention, including monitoring, goal setting, and
      reinforcement; and (3) a 30-day post-intervention follow-up period. Participants
      in the treatment were asked to monitor their BP, sodium, and fluid intake weekly
      for 12 weeks in weekly logs. BP, fluid and sodium logs were reviewed weekly with
      the researcher to determine if goals were met or not met. Reinforcement was given
      for goals met and problem solving offered when goals were not met. The control
      group received standard care. Both systolic and diastolic BPs were significantly
      decreased in the treatment group.

PMID- 22866362
TI  - Work-related emotional stressors and coping strategies that affect the well-being
      of nurses working in hemodialysis units.
AB  - The purpose of this pilot study was to identify and describe work-related
      emotional stressors that impact the well-being of nurses working in hemodialysis
      units and to identify their coping techniques. The literature shows that constant
      exposure to stressors induces emotional conflict and ambiguity, which results in
      the use of coping techniques to balance well-being. Nineteen participants from
      six hemodialysis centers completed the Ways of Coping Questionnaire, a 66-item
      survey based on a four-point scale. Mean and standard deviations were conducted
      on eight coping techniques. Findings revealed that participants most frequently
      used ways of coping were planful problem solving (M = 17266), followed by self
      controlling (M = 15.29), positive appraisal (M = 14.93), and seeking social
      support (M = 14.49) when dealing with work-related stressors.

PMID- 22866363
TI  - Assessment of phosphate binding by sevelamer carbonate powder for oral suspension
      mixed in foods.
AB  - This study investigated mixing sevelamer carbonate powder with foods and
      beverages other than water. Food samples, including applesauce, oatmeal, chicken,
      protein powder, scrambled eggs, ginger ale, and diet ginger ale, were subjected
      to an in vitro assay, and the difference in the amount of phosphate bound between
      samples pre-exposed to foods and samples where the drug was exposed to foods
      concurrently was determined Under these assay conditions, pre-exposure to
      sevelamer carbonate powder had no effect on the ability to bind phosphate.
      Clinical testing is needed to further evaluate this finding.

PMID- 22866364
TI  - Weather emergency!

PMID- 22866366
TI  - A tall order.

PMID- 22866365
TI  - Fall prevention in adults undergoing incenter hemodialysis.

PMID- 22866367
TI  - Church CPR training saves a life.

PMID- 22866368
TI  - JCN on target.

PMID- 22866369
TI  - Diverticular disease 2012 medication update.

PMID- 22866370
TI  - Get connected!

PMID- 22866371
TI  - Simple reassurance.

PMID- 22866372
TI  - Hardness of heart.

PMID- 22866373
TI  - Unhappy? Low morale? Try the 5 languages of appreciation in the workplace.
AB  - Communicating appreciation to staff is critical in healthcare settings today.
      Five specific Languages of Appreciation have been identified that can be
      communicated in individualized ways in the workplace to affirm, encourage,
      mediate stress, and improve employee morale. In tight budget environments, such
      an employee recognition program doesn't require financial resources or a line
      item in the budget.

PMID- 22866374
TI  - When the topic is sex: facilitating parent child communicaton in the faith
      community.
AB  - Significant evidence supports that (a) parent-child connectedness and religion
      are protective factors against adolescent risk behaviors; and (b) children want
      to have conversations with parents about sexuality but parents frequently do not
      feel comfortable or knowledgeable to teach on this sensitive subject. Nurses can
      be instrumental in facilitating communication between parents and children about
      sexuality. This article describes a sexuality workshop provided by nurses in a
      faith community setting.

PMID- 22866375
TI  - Health care missions: changing the local landscape.
AB  - A nurse changed local healthcare access in a remote area by going to serve the
      Aymara people in Bolivia as a missionary after her retirement in the United
      States. Resources for exploring healthcare missions as a second career are
      offered.

PMID- 22866376
TI  - Lament: giving words to nurses' grief.
AB  - Nurses are intimately present with people who are seriously ill, suffering and
      dying--giving rise to the need to cry out and give words to personal pain and
      grief. Practicing a regular rhythm of lament to God as found in the psalms of the
      Bible can assist nurses in coping with grief and prepare them to continue to care
      for the hurting with God's strength and hope.

PMID- 22866377
TI  - Perceptions of the character of God as narrated by East African women living with
      HIV.
AB  - Two qualitative research studies conducted with women living with HIV in Malawi
      (N = 72) and Kenya (N = 54) separately revealed personal faith as a primary
      coping mechanism that mitigates the effects of stigma and promotes spiritual,
      physical, and mental health. Fourth characteristics of God emerged that sustain
      the women in daily life.

PMID- 22866378
TI  - Service-learning abroad: a life-changing experience for nursing students.
AB  - Incorporating service-learning experiences into nursing education is one way to
      help prepare students for practice in a global, culturally diverse society.
      Partnering with a church with a long-term mission program in El Salvador offers
      the nursing school at Old Dominion University opportunity to develop a service
      learning program and support healthcare missions.

PMID- 22866379
TI  - A divine encounter.
AB  - Nurses have unique opportunities to reach beyond circumstances and into the
      hearts of patients. By being open and available, we show compassion in a way that
      fosters respect and trust. In this article, a Christian nurse relays a true
      experience of providing vital spiritual care to a man dying from necrotizing
      fasciitis.

PMID- 22866380
TI  - Is respecting the "quiet place" giving spiritual care?

PMID- 22866381
TI  - Regarding Mrs. Chase.

PMID- 22866382
TI  - Hats off to Christian nurse educators!

PMID- 22866383
TI  - The masterpiece.

PMID- 22866384
TI  - A house divided: freedom, equality, and PPACA.

PMID- 22866385
TI  - Cystic fibrosis infant care challenges in diagnosis and management in the era of
      newborn screening.
AB  - With newborn screening for cystic fibrosis (CF) now accessible in every state in
      the US, more infants are being diagnosed. Currently, no large-scale randomized
      studies are available to assist clinicians in providing evidence-based medical
      care for the youngest CF patients. We review the standard of diagnostic
      evaluation, the sweat test, showing a slightly altered range for infants less
      than 6 months of age. Cystic fibrosis transmembrane conductance regulator (CFTR)
      metabolic syndrome is an entity that can be clinically challenging for parents
      and caregivers. Simply indentifying infants with CF can be challenging. This
      review tries to clarify the CFTR gene and its expressions and the additional
      benefits that may be drawn from newborn screening. We searched literature to
      review guidelines for care of infants with CF, and we reviewed newborn screening
      methods and diagnosis. We focused on early nutritional intervention and lung
      protective strategies to improve growth and lung function outcomes.

PMID- 22866386
TI  - Happy birthday Viagra.

PMID- 22866387
TI  - Response to Board of Medical Licensure and Discipline complaint review process.

PMID- 22866388
TI  - Molecular characterization of denitrifying bacteria isolated from the anoxic
      reactor of a modified DEPHANOX plant performing enhanced biological phosphorus
      removal.
AB  - Enhanced Biological Phosphorus Removal (EBPR) under anoxic conditions was
      achieved using a Biological Nutrient Removal (BNR) system based on a modification
      of the DEPHANOX configuration. Double-probe Fluorescence in Situ Hybridization
      (FISH) revealed that Polyphosphate Accumulating Organisms (PAOs) comprised 12.3
      +/- 3.2% of the total bacterial population in the modified DEPHANOX plant. The
      growing bacterial population on blood agar and Casitone Glycerol Yeast Autolysate
      agar (CGYA) medium was 16.7 +/- 0.9 x 10(5) and 3.0 +/- 0.6 x 10(5) colony
      forming units (cfu) mL(-1) activated sludge, respectively. A total of 121
      bacterial isolates were characterized according to their denitrification ability,
      with 26 bacterial strains being capable of reducing nitrate to gas. All
      denitrifying isolates were placed within the alpha-, beta-, and gamma
      subdivisions of Proteobacteria and the family Flavobacteriaceae. Furthermore, a
      novel denitrifying bacterium within the genus Pseudomonas was identified. This is
      the first report on the isolation and molecular characterization of denitrifying
      bacteria from EBPR sludge using a DEPHANOX-type plant.

PMID- 22866389
TI  - Effects of temperature on bacterial transport and destruction in bioretention
      media: field and laboratory evaluations.
AB  - Microbial activities are significantly influenced by temperature. This study
      investigated the effects of temperature on the capture and destruction of
      bacteria from urban stormwater runoff in bioretention media using 2-year field
      evaluations coupled with controlled laboratory column studies. Field data from
      two bioretention cells show that the concentration of indicator bacteria (fecal
      coliforms and Escherichia coli) was reduced during most storm events, and that
      the probability of meeting specific water quality criteria in the discharge was
      increased. Indicator bacteria concentration in the input flow typically increased
      with higher daily temperature. Although bacterial removal efficiency was
      independent of temperature in the field and laboratory, column tests showed that
      bacterial decay coefficients in conventional bioretention media (CBM) increase
      exponentially with elevated temperature. Increases in levels of protozoa and
      heterotrophic bacteria associated with increasing temperature appear to
      contribute to faster die-off of trapped E. coli in CBM via predation and
      competition.

PMID- 22866390
TI  - Comparison of mechanical pretreatment methods for the enhancement of anaerobic
      digestion of pulp and paper waste activated sludge.
AB  - The conventional anaerobic digestion process, requiring long solids retention
      times (SRTs) to digest solids, is currently viewed as impractical for the pulp
      and paper industry because of high capital costs associated with the construction
      of new digesters. Recent developments in sludge solubilization technology could
      be promising in reducing digester size, which also allows for the potential use
      of decommissioned tanks, both of which can reduce the capital cost. Three
      pretreatment technologies for use with anaerobic digestion were tested on
      laboratory-scale to investigate their feasibility. The SRTs in all three
      digesters systematically decreased from 20 to 3 days. The reference digester was
      fed waste activated sludge (WAS) to serve as the control at the same SRTs. The
      other digesters were fed WAS that had been preconditioned using mechanical
      shearing, sonication, or high-pressure homogenization technology. Anaerobic
      digestion with high-pressure homogenization produced as much methane at 3-day
      mean SRT as that from the reference digester operated at 20-day SRT. Therefore, a
      new digester can theoretically be 85% smaller than a conventional digester. An
      added benefit of WAS to methane conversion is the recovery of nutrients nitrogen
      and phosphorus.

PMID- 22866391
TI  - Sludge age, stability, and safety factor for the biofilm-activated sludge process
      reactor.
AB  - The average sludge age (theta(c)) of the activated sludge process (ASP)-biofilm
      were developed and verified experimentally. In addition, the stability and safety
      factor were investigated against theta(c). through a series of curves. These
      curves are important to explain, in concept, the function of the hybrid system
      under different values of theta(c). The proposed curves of this study are simple
      and can be modified for any specified wastewater. The definition of theta(c) of
      ASP was found to be applicable to the hybrid system after including the biofilm.
      A ratio ranging from 70 to 80% of the total mass of biofilm may be used in the
      definition of theta(c). to give close results with the experimental values.
      Furthermore, the minimum sludge age (theta(c)(M)) does not exist in the hybrid
      reactor because of the presence of biofilm; however, theta(c) should come down to
      a critical value under some specific conditions of the reactor.

PMID- 22866392
TI  - Impacts of amount of impregnated iron in granular activated carbon on arsenate
      adsorption capacities and kinetics.
AB  - Iron-impregnated granular activated carbons (Fe-GAC) can remove arsenic
      effectively from water. In this study, Fe-GACs with iron content of 1.64 to
      28.90% were synthesized using a new multi-step procedure for the investigation of
      effects of iron amount on arsenic adsorption capacities and kinetics. Langmuir
      model satisfactorily fit arsenic adsorption on Fe-GACs. The maximum arsenic
      adsorption capacity (q(m)) increased significantly with iron impregnation and
      reached 1,867 to 1,912 microg/g with iron content of 9.96 to 13.59%. Further
      increase of iron content (> 13.59%) caused gradual decrease of q(m). It was found
      that the amount of impregnated iron showed little impact on the affinity for
      arsenate. Kinetic study showed that the amount of impregnated iron affected the
      arsenic intraparticle diffusion rate greatly. The pseudo-second-order kinetic
      model fit arsenic adsorption kinetics on Fe-GACs better than the pseudo-first
      order model. The arsenic adsorption rate increased with increasing of iron
      content from 1.64% to 13.59%, and then decreased with more impregnated iron
      (13.59 to 28.90%).

PMID- 22866393
TI  - Arsenic desorption from ferric and manganese binary oxide by competitive anions:
      significance of pH.
AB  - Ferric and manganese binary oxide (FMBO) has been used to remediate an arsenic
      (As)-polluted river in China, but insufficient data was available to (1) evaluate
      its effects on the environment and (2) propose a feasible strategy of addressing
      the arsenic-bearing FMBO. The desorption behavior of arsenic in the presence of
      four competitive anions (i.e., phosphate, silicate, sulfate, and bicarbonate) at
      different concentrations was investigated with pH ranging from 3 to 11. The
      presence of these anions promoted the desorption of arsenic from arsenic-bearing
      FMBO and followed the sequence of phosphate > silicate > sulfate approximately
      equal to bicarbonate across a wide pH range. Desorption of arsenate (As[V]) was
      more significant than that of arsenite (As[III]). Sequence dissolution of arsenic
      bearing FMBO particles by NH4-oxalate/oxalic acid and hydrochloric acid were
      performed. The laboratory results indicated that As(III) was primarily occluded
      in the crystalline parts of the FMBO. The desorption behavior of arsenic could be
      described by kinetic models using the Elovich and power function equations under
      different pH conditions and was related to the adsorption of phosphate and
      silicate. pH played an important role in the desorption of arsenic, because of
      its effects on the species distribution of anions, surface charge of the arsenic
      bearing FMBO, and subsequent electrostatic forces between anions and FMBO.

PMID- 22866394
TI  - Effect of freezing on photoreactivation of Escherichia coli and Enterococcus
      faecalis.
AB  - The effect of freezing on photoreactivation of two strains of Escherichia coli
      (ATCC strain 25922 and O157:H7 strain 961019) and two strains of Enterococcus
      faecalis (strain ATCC 51299, vancomycin-resistant and strain ATCC 29212,
      vancomycin-sensitive) following ultraviolet irradiation were examined. The level
      of log photoreactivation of the freezing treated test organisms (frozen at -7, 
      15, or -30 degrees C then thawed at room temperature prior to ultraviolet
      irradiation) was compared with that of the samples that had not been frozen.
      Freezing had obvious impact on the response of the test organisms to visible
      light following ultraviolet irradiation. Significantly lower levels of
      photoreactivation were observed in the freezing treated cells. The effect of
      freezing on the ability of the test microbes to photoreactivate seems to be
      strain and species dependent. Overall, the experimental results suggest that less
      photoreactivation could be expected if freezing is used as a treatment method
      prior to ultraviolet disinfection.

PMID- 22866395
TI  - Brine reuse in ion-exchange softening: salt discharge, hardness leakage, and
      capacity tradeoffs.
AB  - Ion-exchange water softening results in the discharge of excess sodium chloride
      to the aquatic environment during the regeneration cycle. In order to reduce
      sodium chloride use and subsequent discharge from ion-exchange processes, either
      brine reclaim operations can be implemented or salt application during
      regeneration can be reduced. Both result in tradeoffs related to loss of bed
      volumes treated per cycle and increased hardness leakage. An experimentally
      validated model was used to compare concurrent water softening operations at
      various salt application quantities with and without the direct reuse of waste
      brine for treated tap water of typical midwestern water quality. Both approaches
      were able to reduce salt use and subsequent discharge. Reducing salt use and
      discharge by lowering the salt application rate during regeneration consequently
      increased hardness leakage and decreased treatment capacity. Single or two tank
      brine recycling systems are capable of reducing salt use and discharge without
      increasing hardness leakage, although treatment capacity is reduced.

PMID- 22866396
TI  - "It's all about giving back".

PMID- 22866397
TI  - Derby district redevelopment in Colorado: case study on the health impact
      assessment process.
AB  - Health Impact Assessment (HIA) is a tool that is increasingly utilized in the
      U.S. to shape policies that may impact the public's health. Domestic examples of
      HIAs and the process by which they were conducted, however, are rarely documented
      in the peer-reviewed literature. Through an existing relationship with the
      planning department in Commerce City, Colorado, Tri-County Health Department
      (TCHD) was able to identify a proposed redevelopment plan as a candidate for an
      HIA. The HIA focused on potential effects of the proposed redevelopment of
      Commerce City's historic Derby District on residents' physical activity and
      nutrition-related behaviors. This article describes the HIA process used by TCHD.
      Several sources of data were used, including participatory community input on
      walkability and safety, local health behavior data, and maps of health
      influencing environmental characteristics. Using a variety of information sources
      including community input and local health behavior data can be useful in
      conducting HIAs and impacting policies. Local health departments should consider
      cultivating ongoing collaborative partnerships with municipal planning
      departments and community groups to conduct HIAs and to implement
      recommendations.

PMID- 22866398
TI  - Destination tent city: environmental health lessons from the occupy movement.

PMID- 22866399
TI  - Evaluating the communication of environmental permitting decisions in diverse
      communities.
AB  - Environmental communication plays a critical role in addressing the public's
      growing awareness and apprehension about environmental health risks. Although
      opportunities for public participation in environmental health assessments have
      greatly increased, environmental communication among key stakeholders is an
      evolving process. The authors evaluated the communication that occurred among a
      state environmental agency, six Title V operating facilities, and the public
      concerning environmental permitting decisions perceived to impact environmental
      and human health. The authors identify environmental concerns of diverse
      communities, analyze communication among key stakeholders regarding environmental
      permitting decisions, and propose recommendations for practitioners to improve
      environmental communication strategies among these key stakeholders in either
      urban or rural communities.

PMID- 22866400
TI  - Setting a new standard: increasing capacity at the Fort Drum Environmental Health
      Department.

PMID- 22866401
TI  - The National Amyotrophic Lateral Sclerosis (ALS) Registry.

PMID- 22866402
TI  - Establishing the practice of health impact assessment in the United States.

PMID- 22866403
TI  - The rise of the SuperProfessor: the walls of the ivory tower are coming down.

PMID- 22866404
TI  - 2012 federal laws, regulations, and guidelines for aquatic facilities: what you
      need to know to inspect a public pool.

PMID- 22866405
TI  - Lead in drinking water.

PMID- 22866406
TI  - NEHA as a driver of public policy.

PMID- 22866407
TI  - The U.S. Supreme Court decision on PPACA.

PMID- 22866408
TI  - Southern Remedy Healthy Living Fitness Program.

PMID- 22866409
TI  - Outgoing president's address to the Texas Dental Association House of Delegates,
      May 3, 2012.

PMID- 22866410
TI  - Trustee's address to the Texas Dental Association House of Delegates May 3, 2012.

PMID- 22866411
TI  - Incoming president's address to the Texas Dental Association House of Delegates,
      May 6, 2012.

PMID- 22866412
TI  - Oral and maxillofacial pathology case of the month: migratory stomatitis.

PMID- 22866413
TI  - Salivary stimulants and saliva substitutes are equally effective in terms of
      patient-perceived comfort in patients with xerostomia (UT CAT #2188).

PMID- 22866414
TI  - Comparison of technique errors of intraoral radiographs taken on film v
      photostimulable phosphor (PSP) plates.
AB  - OBJECTIVE: The objective of this study was to compare the technical errors of
      intraoral radiographs exposed on film v photostimulable phosphor (PSP) plates.
      METHODS: The intraoral radiographic images exposed on phantoms from preclinical
      practical exams of dental and dental hygiene students were used. Each exam
      consisted of 10 designated periapical and bitewing views. A total of 107 film
      sets and 122 PSP sets were evaluated for technique errors, including placement,
      elongation, foreshortening, overlapping, cone cut, receptor bending, density,
      mounting, dot in apical area, and others. Some errors were further subcategorized
      as minor, major, or remake depending on the severity. The percentages of
      radiographs with various errors were compared between film and PSP by the
      Fisher's Exact Test. RESULTS: Compared with film, there was significantly less
      PSP foreshortening, elongation, and bending errors, but significantly more
      placement and overlapping errors. Using a wrong sized receptor due to the
      similarity of the color of the package sleeves is a unique PSP error.
      CONCLUSIONS: Optimum image quality is attainable with PSP plates as well as film.
      When switching from film to a PSP digital environment, more emphasis is necessary
      for placing the PSP plates, especially those with excessive packet edge, and then
      correcting the corresponding angulation for the beam alignment. Better design for
      improving intraoral visibility and easy identification of different sized PSP
      will improve the clinician's technical performance with this receptor.

PMID- 22866415
TI  - Biologically based treatment of immature permanent teeth with pulpal necrosis: a
      case series.
AB  - This case series reports the outcomes of 8 patients (ages 9-4 years) who
      presented with 9 immature permanent teeth with pulpal necrosis and apical
      periodontitis. During treatment, 5 of the teeth were found to have at least some
      residual vital tissue remaining in the root canal systems. After NaOCI irrigation
      and medication with ciprofloxacin, metronidazole, and minocycline, these teeth
      were sealed with mineral trioxide aggregate and restored. The other group of 4
      teeth had no evidence of any residual vital pulp tissue. This second group of
      teeth was treated with NaOCl irrigation and medicated with ciprofloxacin,
      metronidazole, and minocycline followed by a revascularization procedure adopted
      from the trauma literature (bleeding evoked to form an intracanal blood clot). In
      both groups of patients, there was evidence of satisfactory postoperative
      clinical outcomes (1-5 years); the patients were asymptomatic, no sinus tracts
      were evident, apical periodontitis was resolved, and there was radiographic
      evidence of continuing thickness of dentinal walls, apical closure, or increased
      root length.

PMID- 22866416
TI  - Evaluation of an ameloblastic fibro-odontoma with cone beam computed tomography.
AB  - BACKGROUND: The clinical presentation, radiographic features, and
      histopathological findings of a case of ameloblastic fibro-odontoma are
      described. The clinical and radiographic presentations of this case are typical
      of this benign odontogenic tumor. The patient was young and asymptomatic with the
      exception of the clinical absence of the permanent mandibular left first molar.
      Treatment consisted of simple enucleation with removal of the primary mandibular
      left second molar. METHODS: A panoramic image and cone beam computed tomography
      (CBCT) scan were acquired in order to determine the reason for clinical absence
      of the permanent mandibular left first molar. The CBCT image proved to be a
      valuable supplement to the conventional radiographic examination as it provided
      information not apparent on the 2-dimensional panoramic image. Both the extent of
      the lesion and its effects on adjacent structures were better delineated with
      CBCT. Additionally, the presence of calcifications, an important radiographic
      characteristic of this particular lesion, were visible on CBCT versus the
      panoramic image. CONCLUSIONS: This case report demonstrates that the CBCT scan
      provided important management and treatment planning information that was not
      apparent in the panoramic image.

PMID- 22866417
TI  - Value for your profession. Business insurance: the fundamentals.

PMID- 22866419
TI  - Strategic planning and the NJDA.

PMID- 22866418
TI  - Pay more, get less.

PMID- 22866420
TI  - The successful dental practice part two.

PMID- 22866421
TI  - $1.5 million gift from Delta Dental of New Jersey to improve dental care for
      special needs community.

PMID- 22866422
TI  - Primary oral herpes: diagnosis & management.

PMID- 22866423
TI  - Oral pathology quiz # 75. Case number 1. Epithelial dysplasia.

PMID- 22866424
TI  - Oral pathology quiz # 75. Case number 2. Erythema migrans.

PMID- 22866425
TI  - Oral pathology quiz # 75. Case number 3. Calcifying odontogenic cyst.

PMID- 22866426
TI  - Oral pathology quiz # 75. Case number 4. Systemic medication.

PMID- 22866427
TI  - Probiotics in oral health--a review.
AB  - Probiotics are dietary supplements containing potentially beneficial bacteria or
      yeasts. Probiotics are live microorganisms thought to be beneficial to the host
      organism and, when administered in adequate amounts, confer a health benefit on
      the host. Lactic acid bacteria and bifidobacteria are the most common types of
      microbes used as probiotics. Probiotics strengthen the immune system to combat
      allergies, stress, exposure to toxic substances and other diseases. There are
      reports of beneficial use in HIV infections and cancers.These products help in
      stimulating oral health promoting flora, and suppress the pathologic colonization
      and disease spread. Probiotics can be bacteria, molds and yeast, but most
      probiotics are bacteria. In recent years, there has been a lot of interest in the
      use of probiotics in maintaining good oral health and treating oral infections.
      Their use in premalignant and malignant oral disorders is yet to be probed.

PMID- 22866428
TI  - Invisalign therapy in teeth with clinically short roots.

PMID- 22866429
TI  - Be a 'Betty,' be a mentor.

PMID- 22866430
TI  - Aspire to be engaged.

PMID- 22866431
TI  - Beers criteria for potentially inappropriate medication use in older adults.
AB  - Nurses can decrease the risk of adverse drug problems with medication review and
      prompt interventions. The Beers Criteria lists medications to avoid using among
      elderly clients. The origin of the Beers Criteria, its 2002 modification, and
      application in acute care settings are explained.

PMID- 22866432
TI  - Nursing best practices using automated dispensing cabinets: nurses' key role in
      improving medication safety.
AB  - Automated dispensing cabinets (ADCs) are used widely, but safety gaps remain.
      Nursing-pharmacy collaboration, expert guidance, self-assessment tools,
      compliance with nursing best practices, and continuing education are essential to
      optimize the safety and productivity of ADC use.

PMID- 22866433
TI  - Bedside nurse-to-nurse handoff promotes patient safety.
AB  - Nurse-to-nurse beside handoff allows the oncoming nurse to visualize the patient
      and ask questions of the previous nurse. It encourages pateints to be involved
      actively in their care and allows standardized communication between nursing
      shifts. BACKGROUND: Patient handoff between nurses at shift change has been an
      important process in clinical nursing practice, allowing nurses to exchange
      necessary patient information to ensure continuity of care and patient safety.
      Bedside handoff allows the patient the ability to contribute to his or her plan
      of care. It also allows the oncoming nurse an opportunity to visualize the
      patient and ask questions. This is critical in meeting the Joint Commission's
      2009 National Patient Safety Goals. It encourages patients to be involved
      actively in their care and it implements standardized handoff communication
      between nursing shifts. Bedside handoff promotes patient safety and allows an
      opportunity for patients to correct misconceptions. METHODS: A convenience sample
      of 60 patients was enrolled, 30 before the practice change and 30 after the
      change. All nursing staff were invited to participate. Both patients and staff
      were given self-designed surveys before and after the practice change. RESULTS:
      Fifteen nurses with a mean of 2 years in the profession completed the pre- and
      post-survey. A majority of staff were not satisfied with the current shift change
      report, but statistical improvement was achieved after the practice change. Also,
      statistical improvement was achieved with patients' satisfaction with involvement
      in their plan of care. CONCLUSIONS: Use of bedside nursing handoff promotes staff
      accountability, two-person IV medication reconciliation, and patient
      satisfaction.

PMID- 22866434
TI  - Return of bowel sounds indicating an end of postoperative ileus: is it time to
      cease this long-standing nursing tradition?
AB  - Evidence and rationale supporting return of bowel sounds as an unreliable
      indicator of the end of postoperative ileus after abdominal surgery are provided.
      INTRODUCTION: A loss of gastrointestinal motility, commonly known as
      postoperative ileus (POI), occurs after abdominal surgery. Since the 1900s,
      nurses and other clinicians have been taught to listen for return of bowel sounds
      to indicate the end of POI. Evidence-based nursing literature has challenged this
      long-standing traditional nursing practice. PURPOSE: The purpose of this study
      was to provide evidence from a randomized clinical trial and rationale supporting
      evidence-based inquiry concerning return of bowel sounds as an unreliable
      indicator of the end of POI after abdominal surgery. METHOD: Time (days) of
      return of bowel sounds after abdominal surgery was compared to the time (days) of
      first postoperative flatus, an indicator of the end of POI, in 66 patients
      recovering from abdominal surgery randomized to receive standard care compared to
      those who received standard care plus a rocking chair intervention. FINDINGS:
      Pearson's correlation between time to first flatus and return of bowel sounds for
      combined groups was not significant (r = 0.231, p = 0.062, p < 0.05) indicating
      that time to return of bowel sounds and time to first flatus were not associated.
      CONCLUSIONS: The results of this study provide support to evidence-based inquiry
      that questions the relevance of traditional nursing practice activities such as
      listening to bowel sounds as an indicator of the end of POI.

PMID- 22866435
TI  - Alvimopan for acceleration of GI recovery after bowel resection.
AB  - Nurses play a critical role in the management of postoperative ileus during the
      perioperative phase of recovery. Alvimopan is an oral, peripherally acting, mu
      opioid receptor antagonist that accelerates time to gastrointestinal recovery
      (resolution of postoperative ileus), representing a potential advance in
      management of these patients.

PMID- 22866437
TI  - Perspective of a float pool model in ambulatory care.
AB  - During challenging economic times, health care organizations need to function as
      efficiently and cost-effectively as possible. Use of a float model may help
      nurses meet patient care demands in the ambulatory setting.

PMID- 22866436
TI  - Dialysis and fatigue: implications for nurses--a case study analysis.
AB  - Fatigue is one of the most common symptoms experienced by patients receiving
      dialysis. When patients with chronic kidney disease (CKD) and end-stage renal
      disease are admitted to acute care settings, they require management of their
      often profound fatigue. CKD, renal pathology, and renal fatigue are examined in
      relation to a case study.

PMID- 22866438
TI  - Could it be coronary-subclavian steal syndrome?
AB  - A patient with history of coronary bypass surgery was admitted with chest
      discomfort and noted to have decreased left arm blood pressure. She was found to
      have severe subclavian artery stenosis causing coronary-subclavian steal
      syndrome. Subclavian stenting led to resolution of symptoms and normalization of
      blood pressure.

PMID- 22866439
TI  - Primary hypothyroidism.

PMID- 22866440
TI  - Correlations.

PMID- 22866441
TI  - Ammonia abolishers: antibiotics for hepatic encephalopathy.

PMID- 22866442
TI  - The 2-minute warning part v: conduct a post-game analysis and press conference.

PMID- 22866443
TI  - Relationship-based care: implementing a caring, healing environment.

PMID- 22866444
TI  - Adding patient education of skin cancer and sun-protective behaviors to the skin
      assessment screening on admission to hospitals.

PMID- 22866445
TI  - Patient's page. Dental X-ray safety.

PMID- 22866446
TI  - Faculty spotlight--OU College of Dentistry: Dr. G. Frans Currier. Interview by
      Dr. Frank Miranda.

PMID- 22866447
TI  - ADA statement: Dental X-rays should be used sparingly to reduce radiation risk.

PMID- 22866448
TI  - AHA Expert Committee finds no cause and effect relationship between gum disease
      and heart disease or stroke.

PMID- 22866449
TI  - Looking for TALENT in all the wrong places! Finding the talent you need!

PMID- 22866450
TI  - Clinical: Periapical cemento-osseous dysplasia.

PMID- 22866451
TI  - Making a world of difference.

PMID- 22866452
TI  - Increased fees, low wages.

PMID- 22866453
TI  - Flaws in physician assistant pilot.

PMID- 22866454
TI  - Metal on metal hip replacements.

PMID- 22866455
TI  - Nursing innovation swallowed up.

PMID- 22866456
TI  - Memorial chapel to be repaired.

PMID- 22866457
TI  - The Olga diaries--a day in the life of Olga the intern.

PMID- 22866458
TI  - Evaluation report heavily criticised.

PMID- 22866459
TI  - New constitution voted in but turnout low.

PMID- 22866460
TI  - Arguments for and against the new constitution. "Now the rubber really hits the
      road"--Nuku.

PMID- 22866461
TI  - Arguments for and against the new constitution. Result "controversial and
      divisive"--Brookes.

PMID- 22866462
TI  - Journeying to a new understanding of cultural safety.

PMID- 22866463
TI  - 'A powerful and disruptive position'--a cultural safety pioneer reflects.

PMID- 22866464
TI  - 20 years of cultural safety---how far have we come?

PMID- 22866465
TI  - It's time to legalise love.

PMID- 22866466
TI  - Kidney care and renal disease.

PMID- 22866467
TI  - From patient to nurse---my journey.

PMID- 22866468
TI  - Making the links between cultural safety and let's get real.

PMID- 22866469
TI  - Planning for winter's onset.

PMID- 22866470
TI  - Caring for the dying---lessons learnt in New Zealand.

PMID- 22866471
TI  - Preventing falls and keeping patients safe.

PMID- 22866472
TI  - Immigrant members face huge challenges.

PMID- 22866473
TI  - Appendicitis: the worm still turns.

PMID- 22866474
TI  - Gene Shelby, MD.

PMID- 22866475
TI  - Medical homes, ACOs and population management.

PMID- 22866476
TI  - Arkansas health care payment improvement initiative: overview and the role of
      quality measures.

PMID- 22866477
TI  - CME: Medicaid's coming shortfall. Panel discussion: Arkansas payment initiative.

PMID- 22866478
TI  - The case for mandatory staffing levels is clear.

PMID- 22866479
TI  - Trusts to report on nurse ratio.

PMID- 22866480
TI  - Is nursing's image going through a professional adolescence?

PMID- 22866481
TI  - System leaves junior staff overseeing the most acutely ill.

PMID- 22866482
TI  - Strategies to help adolescents stop smoking.
AB  - Since most people who smoke begin doing so during adolescence, there is a need
      for an effective intervention aimed at this age group. This article looks at the
      factors that increase the probability of smoking and tobacco addiction during
      adolescence, and concludes with some useful approaches to smoking cessation.

PMID- 22866483
TI  - An alcohol withdrawal tool for use in hospitals.
AB  - An estimated 40% of patients admitted with alcohol-related problems to Glasgow
      hospitals are at risk of alcohol withdrawal syndrome (AWS). Not managing them
      effectively can affect the physical and psychological wellbeing of staff and
      other patients. This article describes the development and implementation of a
      tool, the Glasgow Modified Alcohol Withdrawal Scale, to manage patients with AWS.
      It is part of a more comprehensive assessment and management protocol and
      incorporates a protocol to help nurses decide whether to administer fixed-dose or
      symptom-triggered benzodiazepine to these patients.

PMID- 22866484
TI  - Protecting specialist roles in haemoglobin disorders.

PMID- 22866485
TI  - What does the future hold for advanced nursing?
AB  - This third in a three-part series on advanced nursing explores the future demand
      for a flexible but regulated nursing career framework. Part 1 explored the
      historical evolution of advanced nursing, while part 2 discussed the development
      of a governance framework.

PMID- 22866486
TI  - Incentive spirometry after abdominal surgery.
AB  - Patients face various possible complications after abdominal surgery. This
      article examines best practice in guiding and teaching them how to use an
      incentive spirometer to facilitate recovery and prevent respiratory
      complications.

PMID- 22866487
TI  - Staying connected to nursing.

PMID- 22866488
TI  - Get two for the price of one.

PMID- 22866489
TI  - Two faces of a specialty.

PMID- 22866490
TI  - The importance of nurse.

PMID- 22866491
TI  - Looking good.

PMID- 22866492
TI  - On a mission.

PMID- 22866493
TI  - Comfortable in their skin.

PMID- 22866494
TI  - The making of a plastic surgeon.

PMID- 22866495
TI  - Reshaping lives.

PMID- 22866496
TI  - Revising and improving previous work is theme for 2012.

PMID- 22866497
TI  - Lessons for the future.

PMID- 22866498
TI  - Current trends in hand surgery.
AB  - Hand surgery became an established subspecialty between World Wars I and II.
      Prior to this time, hand injuries were cared for by various specialists
      neurosurgeons, plastic surgeons, orthopedic surgeons, and general surgeons-each
      of whom would focus on their particular tissue within the hand. With the nearly
      90,000 hand injuries sustained during World War II, military hospitals were
      created to deal solely with hand injuries, and hand specialists began to treat
      the hand as a single functional organ. This article briefly reviews the origin of
      the field and discusses current trends in hand surgery.

PMID- 22866499
TI  - The evolution of wrinkle removal: use of lasers and other devices in facial
      rejuvenation.
AB  - Lasers have revolutionized facial rejuvenation. Various wavelengths, more
      powerful machines allowing shorter shutter times and more precise vaporization,
      and other innovations led physicians and their patients to embrace ablative laser
      technology. The results have not always been positive, however. Over-adoption by
      poorly trained physicians led to highly publicized problems and the development
      of a whole class of nonablative machines as well as fractional laser technology.
      This article reviews the evolution of wrinkle removal by lasers and other
      devices.

PMID- 22866500
TI  - Craniosynostosis and deformational plagiocephaly: when and how to intervene.
AB  - Craniosynostosis, a congenital deformity in which one or more of the sutures
      between the bones of the cranial vault fuse prematurely, is a relatively rare
      condition that is usually obvious just after birth. Deformational plagiocephaly
      is much more common and usually becomes apparent by 2 months of age. Although the
      head of a baby with deformational plagiocephaly may appear flat on one side,
      deformational plagiocephaly does not affect brain function. Craniosynostosis,
      however, may impair brain growth and development and, thus, is far more serious.
      Babies with irregularly shaped heads that are concerning should be evaluated by a
      craniofacial surgeon. This article provides an overview of the physical signs of
      craniosynostosis and deformational plagiocephaly as well as an update on
      treatment.

PMID- 22866501
TI  - Be careful what you fish for.

PMID- 22866502
TI  - How can you be two places at once when you're not anywhere at all?

PMID- 22866503
TI  - Effects of erythropoietin stimulating agent (ESA) automated adjustment protocols
      on hemoglobin levels and mortality in end stage renal disease patients.

PMID- 22866504
TI  - Cervical manipulation and the myth of stroke.

PMID- 22866505
TI  - Medical marijuana in Huntington's disease: report of two cases.

PMID- 22866506
TI  - Cardiovascular health of HIV-infected African-American women at the Miriam
      Hospital Immunology Center in Providence, RI.

PMID- 22866507
TI  - First steps, a resident-run postpartum support group for a high risk community.

PMID- 22866508
TI  - Using a professional organization, MomDocFamily, to understand the lives of
      physician-mothers.

PMID- 22866509
TI  - Pregnancy outcomes in an initiative preceeding onset of prenatal care.

PMID- 22866510
TI  - Intercoronary connection between the right coronary artery and left circumflex
      artery in the absence of obstructive coronary disease and collaterals.

PMID- 22866511
TI  - "Empty promises from the NMC will not suffice".

PMID- 22866512
TI  - CNO to draw up national strategy.

PMID- 22866513
TI  - "Fast-track sister programme aims to develop the best leaders".

PMID- 22866514
TI  - "Palliative care can sustain and support mental health clients".

PMID- 22866515
TI  - How does stigma affect people with mental illness?
AB  - People with mental health problems experience many different types of stigma.
      This article explores the attitudes and beliefs of the general public towards
      people with mental illness, and the lived experiences and feelings of service
      users and their relatives.

PMID- 22866516
TI  - Case management for tuberculosis.

PMID- 22866517
TI  - Challenging misconceptions about mental health nursing.
AB  - There is continuing stigma surrounding mental ill health and mental health
      nursing. This article examines perceptions of mental health nurses and outlines
      how one university is working to challenge stigma in the field.

PMID- 22866518
TI  - Developing a bundle to improve fluid management.
AB  - Recent reports have highlighted concerns over inadequate patient hydration. A
      team from NHS East of England (now part of NHS Midlands and East) developed the
      intelligent fluid management bundle to support practitioners in ensuring patients
      receive adequate hydration.

PMID- 22866519
TI  - A practical guide to improving end-of-life care.

PMID- 22866520
TI  - Intentional rounding: what is the evidence?

PMID- 22866521
TI  - 60 seconds with Annie Norman.

PMID- 22866523
TI  - Time for a plan B?

PMID- 22866522
TI  - A life devoted to learning.

PMID- 22866524
TI  - To regulate or not to regulate?

PMID- 22866525
TI  - Online training update.

PMID- 22866526
TI  - Midwife and health visitor: precarious, problematic but possible.

PMID- 22866527
TI  - CPHVA awards Health Visitor of the Year.

PMID- 22866528
TI  - Barriers to effective practice for health visitors working with asylum seekers
      and refugees.
AB  - The objective of this study was to determine the barriers to effective practice
      that health visitors experience when working with refugees and asylum seekers.
      This was a qualitative study based on the analysis of in-depth interviews with a
      purposive sample of 14 health visitors describing their experiences working with
      refugees and asylum seekers. These were analysed using the Framework process, a
      thematic matrix-based analytical method. The findings identified that the
      barriers to effectiveness for health visitors when working with refugees and
      asylum seekers were underpinned by ineffective use of services and stretched
      resources. The results imply that commissioners of services need to have an
      understanding of these barriers to commission effectively.

PMID- 22866529
TI  - The practice and attitudes of gypsy and traveller women towards early infant
      feeding.
AB  - This research explores the early infant feeding practice of gypsy and traveller
      women and their attitudes towards breast and formula feeding in one primary care
      trust. This research was undertaken using a quantitative research approach. Two
      structured questionnaires were administered. The first questionnaire was
      completed by all health visitors employed by the trust. This questionnaire
      established that most gypsy and traveller women choose to formula feed their
      infants and the breastfeeding rate in this community is very low. The second
      questionnaire was completed by 50% of the gypsy and traveller community who met
      the inclusion criteria. The Iowa Infant Feeding Attitude Scale (IIFAS) was
      completed as part of this questionnaire. This questionnaire showed that gypsy and
      traveller women had a more neutral attitude towards early infant feeding than was
      expected. This is significant as previous research suggests that women with
      neutral attitude scores are not fixed in their early infant feeding intentions.
      This therefore implies that the infant feeding practice of these women could
      potentially be influenced. This study, therefore, concludes that implementing
      focused interventions aimed at promoting breastfeeding could potentially increase
      the breastfeeding initiation rate in this community.

PMID- 22866530
TI  - Mothers' experiences of their children's detoxification in the home: results from
      a pilot study.
AB  - Detoxification from alcohol and/or drugs and the achievement of abstinence
      without formal treatment is often preferred using community-based supports from
      local GPs and family. Family members are often involved in the sourcing of
      information on detoxification and treatment options, user advocacy and provision
      of remedial supports while detoxifying within the family home. The aim of the
      research was to describe and explore family experiences of self-detoxification
      processes from the perspectives of mothers in the Mid West of Ireland. A
      convenience sample of adult mothers who had experienced their child detoxifying
      in the home (n=9) were interviewed. The findings illustrated varied personal
      definitions of detoxification. Addiction stigma and costly experiences of
      treatment and after care pathways facilitated home detoxification attempts. A
      lack of GP advice, support and information around safe home detoxification was
      observed to contribute to information and support seeking from friends, family
      and community members with home detoxification experience. Self-medication of
      both licit and illicit substances while detoxifying, and relapse cycles were
      common. The research highlights the need for inclusive health and social supports
      provided by GPs, community nurses, RGNs and district nurses for families and
      individuals detoxifying in the home setting.

PMID- 22866531
TI  - Clinical update: febrile convulsion in childhood.
AB  - Febrile convulsion is common in young children and occurs in 3-4% of children
      aged under six years of age. This is the most common seizure disorder and it is
      not epilepsy. It occurs generally with high temperatures and recurs in one third
      of children during a subsequent febrile illness. These episodes can be extremely
      frightening for parents and lot of reassurance needs to be provided by health
      professionals after an episode. Most often the episodes are short lived and self
      terminating and long-term anticonvulsant medicines are not required. The
      prognosis is generally good and affected children do not suffer any long-term
      health problems. Community practitioners can provide education, support and
      counselling to help families return to normality after an event.

PMID- 22866532
TI  - Irritable bowel syndrome in children explained.

PMID- 22866533
TI  - Getting it right for school nursing.

PMID- 22866534
TI  - Could this birthday mark the end of NHS as we know it?

PMID- 22866535
TI  - Abdominal obesity and cardiovascular disease risk factors within body mass index
      categories.
AB  - BACKGROUND: Several organizations recommend the use of measures of abdominal
      obesity in conjunction with body mass index (BMI) to assess obesity-related
      health risk. Recent evidence suggests that waist circumference (WC), waist-to-hip
      ratio (WHR) and waist-to-height ratio (WHtR) are increasing within BMI
      categories. This shift may have affected the usefulness of abdominal obesity
      measures. DATA AND METHODS: Data are from respondents aged 18 to 79 to the 2007
      to 2009 Canadian Health Measures Survey. Using logistic regression, this paper
      examines cardiovascular disease (CVD) risk factors in relation to WC, WHR and
      WHtR within BMI health-risk categories. CVD risk factors considered include
      components of the metabolic syndrome. RESULTS: Among men in the normal and
      overweight BMI categories, WHR and WHtR were positively associated with having at
      least two CVD risk factors. All three abdominal obesity measures were associated
      with increased odds of having at least two CVD risk factors among normal-weight
      women. Abdominal obesity was not associated with CVD risk factors for people in
      obese class I. INTERPRETATION: Among men and women in the normal BMI category,
      measures of abdominal obesity are associated with increased odds of CVD risk
      factors. This underscores the importance of measuring and monitoring abdominal
      obesity in normal-weight men and women.

PMID- 22866536
TI  - Urban sprawl and its relationship with active transportation, physical activity
      and obesity in Canadian youth.
AB  - BACKGROUND: Urban sprawl is a potential environmental influence on youth
      overweight/obesity. However, little is known about the association between urban
      sprawl and behaviours that influence obesity such as active transportation and
      physical activity. METHODS: The study population consisted of 7,017 respondents
      aged 12 to 19 to the 2007/2008 Canadian Community Health Survey, living in
      Canada's 33 census metropolitan areas (CMAs). Factor analysis was used to obtain
      an urban sprawl score for each CMA, incorporating dwelling density, percentage of
      single or detached dwelling units, and percentage of the population living in the
      urban core. Multi-level logistic regression examined whether urban sprawl was
      associated with frequent active transportation (30 or more minutes a day),
      moderate-to-vigorous physical activity (MVPA) (60 or more minutes a day), and
      overweight/obesity. RESULTS: Urban sprawl was associated with active
      transportation among 12- to 15-year-olds, with the relative odds of engaging in
      at least 30 minutes of active transportation per day increasing by 24% (95% CI:
      10-39%) for each standard deviation (SD) increase in the urban sprawl score. For
      the entire sample aged 12 to 19, higher urban sprawl was associated with MVPA
      (odds ratio per SD increase = 1.10, 95% CI: 1.01-1.20), but not with
      overweight/obesity (odds ratio per SD increase = 1.06, 95% CI: 0.94-1.18).
      INTERPRETATION: Urban sprawl was associated with active transportation and MVPA
      in Canadian youth, although in the opposite direction to what has been reported
      in the literature for adults.

PMID- 22866537
TI  - Daily patterns of physical activity among Canadians.
AB  - The 2007 to 2009 Canadian Health Measures Survey (CHMS) collected directly
      measured physical activity on seven consecutive days for a representative sample
      of the population aged 6 to 79. Based on the CHMS, half of the active minutes in
      a day are accumulated between 11:00 a.m. and 5:00 p.m. For children, the most
      active period is lunch-time (11:00 a.m. to 1:00 p.m.), and for teenagers aged 15
      to 19, the after-school period (3:00 p.m. to 5:00 p.m.). Children and youth are
      more active on weekdays than on weekends. Active children and youth tend to
      accumulate more minutes of moderate-to-vigorous physical activity after school,
      whereas active adults do so at lunch time.

PMID- 22866538
TI  - Measures of abdominal obesity within body mass index categories, 1981 and 2007
      2009.
AB  - This article describes measures of abdominal obesity--waist circumference, waist
      to-hip ratio, and waist-to-height ratio--within body mass index (BMI) categories,
      using data from two population-based health surveys. Among normal-weight men, the
      percentages at increased/high health risk based on these three measures were not
      statistically different in 2007-2009 than in 1981. By contrast, among normal
      weight women, increases were observed in the percentage at increased/high health
      risk based on each of the three measures. The percentage of overweight men at
      increased/high risk based on waist circumference rose from 49% in 1981 to 62% in
      2007-2009, and among overweight women, the percentage at increased/high risk rose
      for each of the three measures (64% to 93% for waist circumference, 22% to 51%
      for waist-to-hip ratio, and 68% to 87% for waist-to-height ratio). Although
      substantial percentages of men and women in obese class I were at increased/high
      health risk based on abdominal obesity measures in 1981, by 2007-2009, almost
      everyone in this BMI category was at increased/high risk.

PMID- 22866539
TI  - Prevalence and correlates of folic acid supplement use in Canada.
AB  - Dietary supplements are an important source of folic acid, a nutrient that is
      vital in reducing the risk of neural tube defects. As part of the 2007 to 2009
      Canadian Health Measures Survey, data were collected on supplement use, and
      biomarkers were directly measured. Use of supplements that contain folic acid was
      reported by 25% of Canadians aged 6 to 79. Females were more likely than males to
      report taking folic acid supplements. People who ate fruit and vegetables less
      than once a day had significantly lower odds of taking folic acid-containing
      supplements than did those who ate fruit and vegetables at least three times a
      day. Of those who consumed a folic acid supplement, 91% reported also taking a
      supplement that contained vitamin B12. Red blood cell folate concentrations below
      the median (less than 1,248 nmol/L), low-to-marginal serum vitamin B12
      concentrations (221 pmol/L or less), and high concentrations of plasma
      homocysteine were negatively correlated with folic acid-containing supplement
      use.

PMID- 22866540
TI  - Physical activity, sedentary behaviour and sleep in Canadian children: parent
      report versus direct measures and relative associations with health risk.
AB  - BACKGROUND: The accurate measurement of time devoted to physical activity,
      sedentary pursuits and sleep is difficult and varies considerably between
      surveys. This has implications for population surveillance and understanding how
      these variables relate to health. METHODS: This sample of children (n = 878) was
      from the 2007 to 2009 Canadian Health Measures Survey. Moderate- to-vigorous
      physical activity (MVPA), sedentary behaviour and sleep duration were assessed
      using both a questionnaire and an accelerometer. This article compared parent
      reported and directly measured physical activity, sedentary behaviour and sleep,
      and examined their associations, alone or in combination, with selected health
      markers in children aged 6 to 11. RESULTS: According to parent reports, the
      children in this study had an average of 105 minutes of MVPA, 2.5 hours of screen
      time and 9.7 hours of sleep per day; accelerometers recorded 63 minutes of MVPA,
      7.6 hours of sedentary time and 10.1 hours of sleep per day. MVPA, measured by
      parent-report or accelerometry, was significantly associated with body mass
      index. In a regression model, directly measured MVPA and sleep were significantly
      associated with body mass index, and directly measured MVPA was significantly
      associated with waist circumference. Parent-reported screen time approached a
      significant association with body mass index. INTERPRETATION: Time estimates and
      associations with health markers varied between parent-reported and directly
      measured physical activity, sedentary behaviour and sleep in children. These
      differences are important to understand before the two measurement techniques can
      be used interchangeably in research and health surveillance.

PMID- 22866541
TI  - Biodiversity of termite (Insecta: Isoptera) in tropical peat land cultivated with
      oil palms.
AB  - Termites are the major decomposers in tropical region but yet their occurrences
      in oil palm plantation especially in peat soil are generally treated as pest.
      Study of termite species in peat land was conducted in selected oil palm
      plantations in North Sarawak with 5-7 years old palms and South Sarawak with 13
      15 years old palms with two sites in each area. Results of quadrate (25 x 25 x 30
      cm) sampling showed termite was significantly higher in relative density with
      increasing depth of soil (0-10 = 21.23, 10-20 = 42.52 and 20-30 cm = 81.12%)
      which could be advantaged from being predated by ants (Hymenoptera: Formicidae)
      which were higher in density from soil surface to 10 cm soil depth with relative
      density of 31.84%. Modified transect sampling (50x6 m) had successfully sampled
      18 species of termites from 2 families (Rhinotermitidae and Termitidae), 5
      subfamilies (Rhinotermitinae, Coptotermitinae, Termitinae, Macrotermitinae and
      Nasutitermitinae) and 11 genera (Coptotermes, Schedorhinotermes, Termes,
      Macrotermes, Nasutitermes, Globitermes, Amitermes, Parrhinotermes,
      Pericapritermes, Havilanditermes and Prohamitermes). Both plantation sites have
      termite dominantly feeding on rotten wood as a result of abundant dead woods.
      However, Coptotermes curvignathus Holmgren was identified to feed on the living
      tissues of oil palm causing damage or death of the tree. Study showed higher
      encounter of soil-feeding termite in longer established plantation. It indicates
      the gradually shifting of soil condition towards a stabilized environment which
      favors the successful settlement of soil feeder termite species. Termite control
      should be more targets specific to avoid harming beneficial termites.

PMID- 22866542
TI  - Structural and functional analysis of KIT gene encoding receptor tyrosine kinase
      and its interaction with sunitinib and HDAC inhibitors: an in silico approach.
AB  - KIT is a growth factor receptor, important for normal germ cell migration and
      development. The malfunction of KIT gene results in constitutive activation of
      the tyrosine kinase activity of c-KIT which is believed to be the major oncogenic
      event in stomach, small intestine mastocytosis, acute leukemias, melanomas and
      colon tumors. The genetics of these diseases could be better understood by
      knowing the functional relevance of their SNP variation. In this study, a
      computational analysis to detect the most deleterious nonsynonymous SNPs of KIT
      gene was performed and investigated its binding affinity to native and predicted
      mutant protein structure (D816V) with sunitinib and HDAC (Trichostatin A and
      Panobinostat) inhibitors was investigated. Out of 1,288 SNPs retrieved from dbSNP
      database against KIT gene, 11 non-synonymous SNPs were detected to be damaging
      and deleterious by SIFT, PolyPhen and I-Mutant2.0 servers. Further, we modeled
      the mutant protein based on the deleterious nsSNP (rs121913507) and showed that
      the mutation from Aspartic acid to Valine at 816 position exhibit greatest impact
      on stability. The RMSD values of mutant and native structures are found to be
      0.40 and 1.9 A, respectively. Furthermore, the binding affinity of sunitinib and
      HDAC inhibitors were compared with native and mutant protein. In this regard, it
      was found that trichostatin A has a high binding efficacy towards the mutant
      protein with a binding energy of -35.274 kcal mol(-1), as compared to the native
      structure which has a binding energy of -25.996 kcal mol(-1). Also, the FastSNP
      tool suggested that 3 SNPs found to affect protein splicing site and splicing
      regulation. From present results, it was clear that the non-synonymous SNP
      rs121913507 (D816V) could be the most deleterious SNP for KIT gene and HDAC
      inhibitors can serve as a best drug for the mutant protein.

PMID- 22866543
TI  - Effect of Azotobacter vinelandii and compatible solutes on germination wheat
      seeds and root concentrations of sodium and potassium under salt stress.
AB  - The effect of plant growth-promoting Rhizobacteria (PGPR) and exogenous
      application of compatible solutes on seed germination and root concentrations of
      sodium and potassium of two wheat varieties (Triticum durum L.) were evaluated
      under saline stress. In this experiment, Azotobacter vinelandii strain DSM85,
      glycine betaine and proline were used. Inoculated seeds for each variety were
      placed on Whatman paper in 9 cm Petri dishes containing 15 mL of distilled water
      or NaCl solutions at various concentrations (control, 100, 200, 300 mM)
      supplemented with or without glycine betaine (GB) or proline at 5 mM. The results
      indicated that addition of proline (5 mM) stimulated the production of indol
      acetic acid and the growth of A. vinelandii at 200 and 300 mM NaCl, respectively.
      The germination rate index and the germination final percentage decreased
      significantly (p < 0.05) with increasing salinity level. The germination was
      significantly diminished at 300 mM with significant variation among varieties and
      Waha variety had higher germination percentage than Bousselam variety.
      Inoculation of seeds by A. vinelandii and exogenous application of proline had
      significantly positive effect on the germination at this concentration of NaCl.
      The rate of accumulation of Na+ in roots was important at 100 mM and increased at
      200 mM. The concentration of K+ decreased when salinity increased. The effect of
      inoculation or inoculation with proline decreased the accumulation of Na' and
      reduced the loss of K+ under salt stress. From the present study we can conclude
      that the use of A. vinelandii strain DSM85 and external application of low
      concentrations of proline on seeds might be considered as a strategy for the
      protection of plants under saline stress.

PMID- 22866544
TI  - Characterization and stability of nanostructured lipid carriers as drug delivery
      system.
AB  - Recently more focus has been put to the development of innovative drug-delivery
      systems that includes polymer nanoparticles, emulsions and liposomes and solid
      lipid nanoparticles (SLNs). The SLNs have been proposed to be an alternative
      colloidal drug delivery system. The aim of this study was preparation and
      characterization of solid lipid nanoparticle (SLN) using varieties of emulsifier
      for encapsulation of the drug with poor water solubility. In these study four
      types of solid lipid nanoparticles were prepared based on different compositions
      of palm oil (S154) and lecithin (Lipoid 100) using the high pressure
      homogenization method. The SLN formulation had the following (palm oil+lecithin)
      compositions: SLN-01 (90 + 10%, respectively), SLN-02 (80 + 20%, respectively),
      SLN-03 (70 + 30%, respectively) and SLN-04 (60 + 40%, respectively). The SLNs
      were characterized and the optimum stability factors for one year storage
      determined. The parameters used to characterize the SLNs were particle size and
      polydispersity index (particle sizer), zeta potential (zetasizer), crystallinity
      (differential scanning calorimetry and wide angle X-ray diffraction),
      ultrastructure (transmission electron microscopy). Varying the palm oil and
      lecithin compositions resulted in SLNs of variable sizes and zeta potentials. The
      particle sizes of SLN-01, SLN-02, SLN-03 and SLN-04 were 298.40 +/- 11.80, 255.40
      +/- 3.20, 145.00 +/- 3.39 and 273.00 +/- 86.50 nm, respectively, while the zeta
      potentials were -19.44 +/- 60.00, -19.50 +/- 1.80, -17.83 +/- 10.00 and -13.33 +/
      2.30 mV, respectively. Thermoanalysis and X-ray diffraction analysis showed that
      the SLNs had lower crystallinity than bulk lipid. The SLNs were generally round
      and uniform in shape under transmission electron microscopy. The SLN dimensional
      data suggested they had high quality physicochemical characteristics, which are
      conducive for the loading of poor water solubility drugs.

PMID- 22866545
TI  - Comparison of vitamin D deficiency and secondary hyperparathyroidism in obese and
      non-obese children and adolescents.
AB  - Obesity subjects individuals into metabolic and endocrine disorders. Thus obesity
      may increase the risk of vitamin D deficiency. This text aims at studying the
      prevalence of vitamin D deficiency and secondary hyperparathyroidism in obese
      children. In a non-randomized case control study on 52 obese children (body mass
      index (BMI) >95th percentile) aged 4 to 16 years undertaken at the outpatient
      endocrine clinic of the Children Hospital at Tabriz University between 2009-2011.
      This study was conducted to compare the prevalence of vitamin D deficiency and
      secondary hyperparathyroidism in obese children compared with 57 non obese (BMI <
      85th percentile). 109 children including 52 (50.5%) boys and 57 (49.5%) girls
      were studied. Most of case (76.9%) and control (42.1%) groups suffered from
      degrees of vitamin D deficiency. There was meaningful statistical difference
      between two groups considering to vitamin D deficiency and parathyroid hormone (p
      = 0.001). A negative relations was found between iPTH and vit D level (p < 0.001,
      r = -0.2), BMI and 25-OH vit D (p < 0.001, r = -0.2). A positive relation was
      observed between parathyroid hormone and BMI (p = 0.009, r = 0.1). Obese children
      are at high risk at vitamin D deficiency and secondary hyperparathyroidism. BMI
      appears to be an important risk factor for vitamin D deficiency.

PMID- 22866546
TI  - Phytochemical investigation and in vitro antinociceptive activity of Clerodendrum
      indicum leaves.
AB  - The crude ethanolic extracts of Clerodendrum indicum Linn. leaves were
      investigated for possible antinociceptive activity using acetic acid induced
      writhing model in mice. Phytochemical analysis was also carried out according to
      the standard procedures to identify the presence of different phytoconstituents
      in the ethanolic extract of the plant leaves. The study results showed 38.91 and
      55.24% inhibition of writhings in the tested mice when ethanolic extract of
      Clerodendrum indicum Linn. leaves at doses of 250 and 500 mg kg(-1) body weight
      was given intraperitoneally, respectively. The study results were also compared
      with antinociceptive activity of the standard drug, Diclofenac sodium (68.37%
      inhibition) used at 25 mg kg(-1) body weight. At the above doses, the crude
      ethanolic extract of the plant showed significant antinociceptive activity in
      dose dependent fashion in acetic acid-induced writhing model in mice. The
      inhibition of writhings was calculated in respective to control group and it was
      found that p-values (<0.0001) obtained in all cases were extremely statistically
      significant. However, the phytochemical analysis showed the presence of alkaloid,
      steroid, saponin, tannin, reducing sugar and gum. The results suggest that crude
      ethanolic extracts of Clerodendrum indicum leaves possess significant
      antinociceptive properties justifying its folkloric use as analgesics and further
      research is necessary to isolate the principle phytochemical constituent(s)
      responsible for this activity.

PMID- 22866547
TI  - Increasing antimicrobial resistance among Shigella isolates in the Bushehr, Iran.
AB  - Antibiotics are drugs used for treatment of infections caused by bacteria. Misuse
      and overuse of these drugs have contributed to phenomena known as antibiotic
      resistance. In this research, the antimicrobial resistance of the Shigella has
      been determined. This descriptive research analyzed registered laboratory data of
      patients referred to Fatemeh Zahra Hospital of the Bushehr, Iran. Shigella was
      isolated from their cultured sample from the year 2002-2008. In this study, the
      total of 121 registered Shigella collected from 2002-2008 were analyzed. There
      were 62 cases of S. sonnei, 46 cases of S. flexneri, eight cases of S. boydii and
      five cases of S. dysenteriae among them. Furthermore, two cases of Shigella
      sonnei were collected from the blood and the rest from the watery stools of the
      infected patients. The following is the resistance pattern of these organisms; to
      ciprofloxacin, 4.25%; ceftizoxime, 8.62%; nalidixic acid, 12.12%; co-trimoxazole,
      86.13% and to tetracycline, 93.02%. Results ofantibiogram showed that highest
      rate of drug resistance belongs to tetracycline and co-trimoxazole and the lowest
      belongs to ciprofloxacin and ceftizoxime. One of the important issue for
      clinicians, now a day is drug resistance of microorganisms. This phenomenon is
      increasing due to some factors such as improper use of antibiotics and irrational
      prescribing. These factors lead to development of new drug resistant species.

PMID- 22866548
TI  - Natural immunity to hemophilus influenza type b in children, south of Iran: need
      for vaccination.
AB  - Hemophilus influenza type b (Hib) infection has a high morbidity and mortality
      rate especially in children less than 5 years of age. The incidence of Hib
      disease in Iran is not known and Hib vaccine is not included in the National
      Immunization Program. The aim of the present study was to investigate the level
      of antibody to Hib of children five years or younger living in Jahrom, Iran.
      Three hundred eighty six children 5 years or younger were selected by random
      sampling method. A blood samples were taken from those children. Anti-Hib IgG
      antibody (anti-PRP) level was determined in the serum by using anti-Hemophilus
      influenza IgG EIA kit (IBL, Germany). An anti-PRP antibody levels of 0.15 microg
      mL(-1) and over were accepted as the natural immunity. The mean concentration of
      Hib antibody was 0.94 +/- 0.480 microg mL(-1). Natural immunity was determined in
      three hundred and twenty six (84.5%) of the children. The proportion of natural
      immunity was increased from 64.9% among children = 12 month old to 95.2% in
      children aged 49-60 month (p < 0.001). The exposure rate of children with Hib was
      higher than expected, even in children who were just a few months old. Present
      data revealed need to be introducing Hib conjugate vaccine in the National
      Immunization Programs.

PMID- 22866549
TI  - Research is part of real life.

PMID- 22866550
TI  - Insight into the challenges faced by students involved in real-world research.

PMID- 22866551
TI  - Exchange and equality during data collection: relationships through story sharing
      with lesbian mothers.
AB  - AIM: To explore how reciprocity is achieved through a method of self-disclosure,
      namely story sharing. BACKGROUND: Self-disclosure through story sharing promotes
      trusting relationships between researchers and participants that support the
      collection of high quality data, particularly when participants are members of a
      marginalised group and may feel especially vulnerable when sharing sensitive
      information. DATA SOURCES: A qualitative study that examined the experiences of
      lesbian mothers. REVIEW METHODS: Strategies were carefully and deliberately
      implemented to engage in story sharing with the participants. DISCUSSION:
      Participants said that it made a positive difference to how safe and comfortable
      they felt once they knew at least some of the researcher's story. CONCLUSION: The
      collection of rich data is improved by using story sharing as a means of
      establishing reciprocity in qualitative research. IMPLICATIONS FOR
      PRACTICE/RESEARCH: Story sharing has the potential to improve the quality of the
      data collected in qualitative studies. However, strategies that promote the
      emotional safety of the researcher in this context will need further exploration.

PMID- 22866552
TI  - A personal insight into researcher positionality.
AB  - AIM: To highlight observations on the dilemmas of insider research. BACKGROUND:
      Researchers in qualitative research have traditionally been thought of as
      positioned inside or outside the social group being studied. However, there is
      recognition of the blurring of the apparent Separation between these two
      positions. This paper discusses the ethical and methodological dilemmas involved
      as an 'insider' when negotiating access to the field and recruiting participants.
      REVIEW METHODS: This is a reflective paper. CONCLUSION: The personal insight into
      researcher positionality provided in this paper shows that qualitative
      researchers need to consider carefully the potential risks to participants when
      conducting insider research.

PMID- 22866553
TI  - Challenges that may arise when conducting real-life nursing research.
AB  - AIM: To reveal some of the unexpected occurrences that can arise during real-life
      investigations to upset the conventional research process. BACKGROUND: As novice
      investigators develop their careers, they are increasingly likely to encounter
      aspects of research that are rarely mentioned in nursing textbooks. This paper
      sets out several such occurrences that may challenge the researcher and the
      practical consequences for an unsuspecting investigator. DATA SOURCES: The
      author's experience in research over the past 30 years. DISCUSSION: In seeking to
      find satisfactory solutions to problems during research, researchers will also
      face dilemmas that offer at least two possibilities, neither of which may be
      acceptable. Experienced researchers will recognise this situation and acknowledge
      the range of trade-offs that characterise social research. IMPLICATIONS FOR
      PRACTICE/RESEARCH: Novice researchers should be forewarned of some of the
      challenges they could face when carrying out future research.

PMID- 22866554
TI  - How to create a journal article from a thesis.
AB  - AIM: To identify strategies to assist in the publication of research arising from
      a postgraduate thesis or dissertation. BACKGROUND: There are many benefits to
      publishing a journal article from a completed thesis, including contributing
      knowledge to the writer's chosen field, career enhancement and personal
      satisfaction. However, there are also numerous obstacles for the newly graduated
      student in crafting an article fit for a specialist publication from a thesis.
      DATA SOURCES: The author conducted a search of the title, abstract and keywords
      of the Cinahl, Scopus and Proquest databases, from 1990 to 2010: The author
      searched for the words: 'journal article' or 'manuscript; 'thesis' or
      'dissertation'. REVIEW METHODS: The author excluded papers if: they pertained to
      allocation of authorship to someone other than the academic adviser; related to
      undergraduate issues rather than graduate dissertations; were discussions of the
      merits of a PhD by 'publication' instead of 'by thesis'; were not published in a
      peer-reviewed journal; or were not in English. CONCLUSION: The relationship
      between adviser and student changes as the student becomes a graduate, and new
      roles for the student and adviser need to be negotiated. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Students need to realise that writing a paper from a thesis is
      usually going to be more difficult than they anticipate, but the application of
      strategies discussed in this paper should make the task manageable. Furthermore,
      universities might wish to consider alternatives in which published papers emerge
      before the examination of a thesis, such as requiring students to write a paper
      as part of their coursework.

PMID- 22866555
TI  - Parental involvement in neonatal pain management: reflecting on the researcher
      practitioner role.
AB  - AIM: The objective of this paper is to identify and explore some of the ethical
      and professional issues facing the clinical researcher-practitioner and to
      discuss how these were addressed in one particular study. BACKGROUND: The
      author's experience of undertaking ethnographic research in the organisation in
      which she works as a nurse consultant highlighted a number of ethical and
      professional dilemmas. This paper discusses how some of these issues,
      particularly relating to informed consent, confidentiality, practice concerns and
      exploitation were addressed. DATA SOURCES: Doctoral research (DMedSCi) with
      Sheffield University. DISCUSSION: This paper discusses the ethical and
      professional dilemmas and some of the advantages associated with the researcher
      practitioner role. CONCLUSION: This paper identifies and discusses the need to:
      Remember who the research is about and whom it should benefit. Include a wide
      research team. Acknowledge the researcher's responsibility towards the
      participants. Identify and act on problems as they arise. IMPLICATION FOR
      RESEARCH/PRACTICE: The need to keep the participant as the focus of the research,
      to involve a wide research team and to reflect constantly on the process.

PMID- 22866556
TI  - The effect of interview recording on quality of data obtained: a methodological
      reflection.
AB  - AIMS: This article reflects the author's experience of qualitative interviews
      during his research project. It attempts to highlight how recording interviews
      can affect data collection and data quality. BACKGROUND: While recording helps
      researchers keep accurate records of interviews, which in turn assists them
      during their data analysis, its effect on data quality has not been clarified in
      nursing literature. DISCUSSION: The research experience highlighted that
      interview participants, especially those involved in group interviews, were
      reluctant to give permission for recording and were less comfortable and more
      formal when being recorded. CONCLUSION: The preparation for, and how the
      interview is carried out, can either reduce or further accentuate the effect of
      interviewing and recording on the participant. Therefore, appropriate strategies
      to reduce the effects should be implemented. IMPLICATIONS FOR RESEARCH/PRACTICE:
      This article suggests strategies to minimise the effects of interviewing and
      recording of interviews on the participants and hence enhance the quality of data
      obtained.

PMID- 22866557
TI  - Regional follow up of late preterm neonatal intensive care graduates.
AB  - AIM: To guide researchers who are contemplating embarking on research by
      discussing the methodological challenges encountered in a retrospective follow-up
      study of three-year-old, late preterm infants (LPIs) who received neonatal
      intensive care (NIC) in Northern Ireland in 2006. BACKGROUND: The importance of
      effective research examining the longer term outcomes of infants admitted to NIC
      has received increasing recognition. Follow-up cohort and longitudinal studies
      have grown in number globally, yet the research methodology relating to follow up
      of NIC graduates is unclear. DATA SOURCES: Neonatal Intensive Care Outcomes and
      Research Evaluation (NICORE) database; maternity unit delivery records. REVIEW
      METHODS: This is a reflective-practice methodology paper. DISCUSSION: This paper
      highlights the methodological challenges of conducting retrospective follow-up
      research, from the initial planning stages through to the collection of data from
      the children, including identification of infants from a retrospective database,
      ethical issues, child-safety concerns and recruitment challenges. CONCLUSION: The
      important lessons learned from this study were that: Input from a
      multidisciplinary team is central to the success of the study. Protocols and
      guidelines should be in place before the study to ensure that problems are dealt
      with quickly. A realistic timeframe for each phase and ongoing monitoring of
      recruitment rates are essential. IMPLICATIONS FOR RESEARCH/PRACTICE: This paper
      creates an awareness of potential issues that may arise in follow-up research
      with NIC graduates. The paper also offers practical and effective examples of
      dealing with these issues, helping to ensure the smooth running of an ethical,
      professionally conducted, methodologically sound and clinically relevant follow
      up study.

PMID- 22866558
TI  - RCN research pages provide a valuable online resource.

PMID- 22866559
TI  - Where should I send this manuscript?

PMID- 22866560
TI  - On the doctor of nursing practice (DNP).

PMID- 22866561
TI  - Indulgence, restraint, and the engagement of pleasure: inciting reflection using
      Nietzsche's ascetic ideal.
AB  - As part of an interview-based study of gay circuit parties in Montreal, Canada,
      which involved 17 gay and bisexual men, it was noted that participants were
      preoccupied with the topics of indulgence and restraint, particularly in relation
      to their perceptions of social norms regarding acceptable sexual behaviors.
      Theoretically, these findings were examined from a post-structuralist perspective
      using Nietzsche's conceptualization of the ascetic ideal. The outcome of this
      analysis is an alternative conceptualization about the intersections between
      indulgence, pain, guilt, pleasure, and sexually transmitted infection.

PMID- 22866562
TI  - Human-canine interaction: exploring stress indicator response patterns of
      salivary cortisol and immunoglobulin A.
AB  - A repeated measures design was used to analyze the effect of a canine interaction
      on salivary cortisol and immunoglobulin A (IgA) in 33 adults; 16 were pet owners
      and 17 were non-pet owners. Cortisol and IgA levels before and after a canine
      interaction (experimental) or viewing a canine movie (control) were measured by
      enzyme-linked immunosorbent assay and spectrophotometer. Data show a significant
      interaction effect for salivary cortisol in non-pet owners (p = 0.003). Changes
      in IgA levels were not significant. The findings suggested that interaction with
      canines may help reduce the biological effects of stress that influences human
      health. Further studies with larger sample sizes are necessary to support these
      results.

PMID- 22866563
TI  - Effects of vaginal douching education on Turkish women's vaginal douching
      practice.
AB  - BACKGROUND: Vaginal douching (VD) is a very common practice in Turkish culture.
      This practice is affected by individual and cultural characteristics. PURPOSE:
      The aim of the research was to determine how the education based on Pender's
      health promotion model (HPM) affects women's decision to quit vaginal douche and
      the factors that cause women to continue VD practices. METHODS: The HPM guided
      the 2-hr education process. The sample has 58 women. RESULTS: As a result, the
      model education-based HPM helped 69% of women to quit VD practice. It was also
      determined that education affected women who performed VD to feel clean and to
      comply with the religion but was less effective in women who had lower education
      or performed VD to comply with the husband's demand. CONCLUSIONS: Finally, the
      study showed that the education based on HPM affected the women to change their
      attitude toward VD and quit it.

PMID- 22866564
TI  - Theoretical perspective: resilience in medically fragile adolescents.
AB  - Medically fragile adolescents require medical technology and skilled care from
      parents and nurses in daily life. These adolescents may be ventilator dependent,
      require intravenous nutrition or medications, depend on nutritional or
      respiratory support, and depend on nursing care or other medical devices for
      daily living. Much of the extant research on medically fragile children and
      adolescents has lacked an overarching theoretical perspective. Findings suggest
      that peer relationships, family support, technology dependence, school
      attendance, and self-esteem are concepts of relevance for these adolescents.
      Thus, a theoretical framework derived from the risk and resilience literature was
      developed to identify the nature of their interrelationships using theory
      derivation techniques. The resilience in medically fragile adolescents framework
      was derived using concepts described by these adolescents. Further study is
      needed to test this model in medically fragile adolescents with hopes to foster
      positive outcomes for these adolescents.

PMID- 22866565
TI  - Public health issues should trump politics, advocates of safe injection sites
      urge.

PMID- 22866566
TI  - Scripted rounding.

PMID- 22866567
TI  - A new approach to retaining older workers.

PMID- 22866568
TI  - Who is the clinical nurse specialist?

PMID- 22866569
TI  - Nursing in New Brunswick: on the cusp of change.

PMID- 22866570
TI  - Scope for a stimulating career.

PMID- 22866571
TI  - Small-town nurses think big.

PMID- 22866572
TI  - Oats and health: a research update.

PMID- 22866573
TI  - Staying true to self.

PMID- 22866574
TI  - Shared responsibility? Family caregivers and home care nurses.

PMID- 22866575
TI  - Trends in primary particulate matter emissions from Canadian agriculture.
AB  - Particulate matter (PM) has long been recognized as an air pollutant due to its
      adverse health and environmental impacts. As emission of PM from agricultural
      operations is an emerging air quality issue, the Agricultural Particulate Matter
      Emissions Indicator (APMEI) has been developed to estimate the primary PM
      contribution to the atmosphere from agricultural operations on Census years and
      to assess the impact of practices adopted to mitigate these emissions at the soil
      landscape polygon scale as part of the agri-environmental indicator report series
      produced by Agriculture and Agri-Food Canada. In the APMEI, PM emissions from
      animal feeding operations, wind erosion, land preparation, crop harvest,
      fertilizer and chemical application, grain handling, and pollen were calculated
      and compared for the Census years of 1981-2006. In this study, we present the
      results for PM10 and PM2.5, which exclude chemical application and pollen sources
      as they only contribute to total suspended particles. In 2006, PM emissions from
      agricultural operations were estimated to be 652.6 kt for PM10 and 158.1 kt for
      PM2.5. PM emissions from wind erosion and land preparation account for most of PM
      emissions from agricultural operations in Canada, contributing 82% of PM10 and
      76% of PM2.5 in 2006. Results from the APMEI show a strong reduction in PM
      emissions from agricultural operations between 1981 and 2006, with a decrease of
      40% (442.8 kt) for PM10 and 47% (137.7 kt) for PM2.5. This emission reduction is
      mainly attributed to the adoption of conservation tillage and no-till practices
      and the reduction in the area of summer fallow land.

PMID- 22866577
TI  - Estimation of hydrogen sulfide emission rates at several wastewater treatment
      plants through experimental concentration measurements and dispersion modeling.
AB  - The management and operation of wastewater treatment plants (WWTP) usually
      involve the release into the atmosphere of malodorous substances with the
      potential to reduce the quality of life of people living nearby. In this type of
      facility, anaerobic degradation processes contribute to the generation of
      hydrogen sulfide (H2S), often at quite high concentrations; thus, the presence of
      this chemical compound in the atmosphere can be a good indicator of the
      occurrence and intensity of the olfactory impact in a specific area. The present
      paper describes the experimental and modelling work being carried out by CEAM-UMH
      in the surroundings of several wastewater treatment plants located in the
      Valencia Autonomous Community (Spain). This work has permitted the estimation of
      H2S emission rates at different WWTPs under different environmental and operating
      conditions. Our methodological approach for analyzing and describing the most
      relevant aspects of the olfactory impact consisted of several experimental
      campaigns involving intensive field measurements using passive samplers in the
      vicinity of several WWTPs, in combination with numerical simulation results from
      a diagnostic dispersion model. A meteorological tower at each WWTP provided the
      input values for the dispersion code, ensuring a good fit of the advective
      component and therefore more confidence in the modelled concentration field in
      response to environmental conditions. Then, comparisons between simulated and
      experimental H2S concentrations yielded estimates of the global emission rate for
      this substance at several WWTPs at different time periods. The results obtained
      show a certain degree of temporal and spatial (between-plant) variability
      (possibly due to both operational and environmental conditions). Nevertheless,
      and more importantly, the results show a high degree of uniformity in the
      estimates, which consistently stay within the same order of magnitude.

PMID- 22866576
TI  - Transformation of microflora during degradation of gaseous toluene in a biofilter
      detected using PCR-DGGE.
AB  - A laboratory-scale biofiltration system, the rotatory-switching biofilter (RSB),
      was operated for 199 days using toluene as a model pollutant. The target gaseous
      pollutant for the biofiltration experiment was approximately 300 ppmv of toluene.
      Toluene removal efficiency (RE, %) was initially approximately 20% with a 247
      ppmv concentration (0.9 g m(-3)) of toluene during the first 10 days. Although
      the RE decreased several times whenever nitrogen was consumed, it again reached
      almost 100% when the nitrogen source was in sufficient supply. Denaturing
      gradient gel electrophoresis (DGGE) analysis was employed to assess the
      transformation ofmicroflora during operation of the biofilter The results based
      on a 16S rRNA gene profile showed that the microbial community structure changed
      with operation time. Although the microflora changed during the initial period
      (before day 40), transformation of the bacterial component was hardly observed
      after day 51. Statistical analyses of the DGGE profiles indicated that the
      bacterial community was almost unaffected by the environmental factors, such as
      adding ozone, high-level nitrogen supply, increase of loading toluene, and the
      shutdown of the RSB. The DGGE profile using tmoA-like genes, which encode
      proteins belonging to the hydroxylase component mono-oxygenases involved in the
      initial attack of aerobic benzene, toluene, ethylbenzene, and xylene degradation,
      confirmed the existence of toluene-degrading bacteria. There were at least four
      kinds of toluene-degradable bacteria having tmoA-like genes up to day 36, which
      decreased to two species after day 40. Sequence analysis after DGGE profiling
      revealed that Burkholderia cepacia, Sphingobacterium multivorum, and Pseudomonas
      putida were present in the biofilter. Only Alicycliphilus denitrificans was
      present throughout the whole operation period. In the initial stage of operating
      the RSB, many types of bacteria may have tried to adapt to the conditions, and
      subsequently, only selected bacteria were able to grow and to degrade toluene.

PMID- 22866578
TI  - Effects of foliar application with compost tea and filtrate biogas slurry liquid
      on yield and fruit quality of washington navel orange (Citrus sinenesis Osbeck)
      trees.
AB  - Sixteen-year-old navel orange trees at a private orchard located in Kafer El
      Sheikh Governorate, Egypt, were used in this study. Compost tea (CT) and filtrate
      biogas slurry liquid (FLB) were applied at two different concentrations (50% and
      100%); control trees were sprayed with water Trees treated with CT at 100% were
      the highest in yield, fruit weight, and vitamin C, whereas the highest percentage
      of fruit set, fruit number and soluble solid content (SSC), lowest fruit drop,
      and highest reducing and total sugars were in trees treated with 100% FLB.
      Concentrations at 50% for both foliar application (CT and FLB) improved yield and
      fruit characteristics than control treatment. Generally, using a foliar
      application of compost tea and filtrate biogas slurry liquid at (100%) treatments
      as food nutrients could be recommended to improve the yield and fruit quality of
      navel orange fruits under the current study conditions.

PMID- 22866579
TI  - Assessment of heterogeneity of metal composition of fine particulate matter
      collected from eight U.S. counties using principal component analysis.
AB  - The main objectives of this study are to (1) characterize chemical constituents
      of particulate matter (PM) and (2) compare overall differences in PM collected
      from eight US. counties. This project was undertaken as a part of a larger
      research program conducted by the Johns Hopkins Particulate Matter Research
      Center (JHPMRC). The goal of the JHPMRC is to explore the relationship between
      health effects and exposure to ambient PM of differing composition. The JHPMRC
      collected weekly filter-based ambient fine particle samples from eight US.
      counties between January 2008 and January 2010. Each sampling effort consisted of
      a 5-6-week sampling period. Filters were analyzed for 25 metals using inductively
      coupled plasma mass spectrometry (ICP-MS). Overall compositional differences were
      ranked by principal component analysis (PCA). The results showed that weekly
      concentrations of each element varied 3-40 times between the eight counties. PCA
      showed that the first five principal components explained 85% of the total
      variance. The authors found significant overall compositional differences in PM
      as the average of standardized principal component scores differed between the
      counties. These findings demonstrate PCA is a useful tool to identify the
      differences in PM compositional mixtures by county. These differences will be
      helpful for epidemiological and toxicological studies to help explain why health
      risks associated with PM exposure are different in locations with similar mass
      concentrations of PM.

PMID- 22866580
TI  - Cancer values of prevented fatalities (VPFs), one size does not fit all: the
      benefits of contaminated site cleanups in Italy.
AB  - The authors conducted a survey based on conjoint choice experiments in Milan,
      Italy, about mortality risk reductions delivered by hypothetical private
      behaviors and public programs, and used it to estimate the value of a prevented
      fatality (VPF) when the cause of death is cancer. Their estimate of the VPF is
      4.2 million Euros. The VPF is about C1 million larger when the risk reduction is
      delivered by a public program, but further analyses reveal that it is so only
      when the respondent believes that public programs are effective at reducing this
      particular type of mortality risk This estimate of the VPF is higher than generic
      European Union-wide figures recommended by the European Commission Directorate
      General for Environment (DG Environment) for environmental policy analyses, and
      is comparable to other VPFs that are appropriate for Italy, hazardous waste
      regulations, and enforcement-based cleanup programs. The authors use their VPF to
      compute the benefits of addressing leaking landfills, illegal disposal of
      hazardous wastes, and poor hazardous waste management practices in the provinces
      of Naples and Caserta in southern Italy. The authors also examine the importance
      of the discount rates, since the mortality benefits of remediation begin in 20 yr
      and are assumed to continue over 30 yr.

PMID- 22866581
TI  - Enhanced mercuric chloride adsorption onto sulfur-modified activated carbons
      derived from waste tires.
AB  - A number of activated carbons derived from waste tires were further impregnated
      by gaseous elemental sulfur at temperatures of 400 and 650 degrees C, with a
      carbon and sulfur mass ratio of 1:3. The capabilities of sulfur diffusing into
      the micropores of the activated carbons were significantly different between 400
      and 650 degrees C, resulting in obvious dissimilarities in the sulfur content of
      the activated carbons. The sulfur-impregnated activated carbons were examined for
      the adsorptive capacity of gas-phase mercuric chloride (HgC1) by
      thermogravimetric analysis (TGA). The analytical precision of TGA was up to 10(
      6) g at the inlet HgCl2 concentrations of 100, 300, and 500 microg/m3, for an
      adsorption time of 3 hr and an adsorption temperature of 150 degrees C,
      simulating the flue gas emitted from municipal solid waste (MSW) incinerators.
      Experimental results showed that sulfur modification can slightly reduce the
      specific surface area of activated carbons. High-surface-area activated carbons
      after sulfur modification had abundant mesopores and micropores, whereas low
      surface-area activated carbons had abundant macropores and mesopores. Sulfur
      molecules were evenly distributed on the surface of the inner pores after sulfur
      modification, and the sulfur content of the activated carbons increased from 2
      2.5% to 5-11%. After sulfur modification, the adsorptive capacity of HgCl2 for
      high-surface-area sulfurized activated carbons reached 1.557 mg/g (22 times
      higher than the virgin activated carbons). The injection of activated carbons was
      followed by fabric filtration, which is commonly used to remove HgCl2 from MSW
      incinerators. The residence time of activated carbons collected in the fabric
      filter is commonly about 1 hr, but the time required to achieve equilibrium is
      less than 10 min. Consequently, it is worthwhile to compare the adsorption rates
      of HgCl2 in the time intervals of < 10 and 10-60 min.

PMID- 22866582
TI  - Hydrothermal treatment for inactivating some hygienic microbial indicators from
      food waste-amended animal feed.
AB  - To achieve the hygienic safety of food waste used as animal feed, a hydrothermal
      treatment process of 60-110 degrees C for 10-60 min was applied on the separated
      food waste from a university canteen. Based on the microbial analysis of raw
      waste, the inactivation of hygienic indicators of Staphylococcus aureus (SA),
      total coliform (TC), total aerobic plate counts (TPC), and molds and yeast (MY)
      were analyzed during the hydrothermal process. Results showed that indicators'
      concentrations were substantially reduced after hydrothermal treatment, with a
      greater reduction observed when the waste was treated with a higher temperature
      and pressure and a longer ramping time. The 110 degrees C hydrothermal treatment
      for 60 min was sufficient to disinfect food waste as animal feed from the
      viewpoint of hygienic safety. Results obtained so far indicate that hydrothermal
      treatment can significantly decrease microbial indicators' concentrations but
      does not lead to complete sterilization, because MY survived even after 60 min
      treatment at 110 degrees C. The information from the present study will
      contribute to the microbial risk control of food waste-amended animal feed, to
      cope with legislation on food or feed safety.

PMID- 22866583
TI  - Chemical characterization and factor analysis of PM2.5 in two sites of Monterrey,
      Mexico.
AB  - The Monterrey Metropolitan Area (MMA) has shown a high concentration of PM2.5 in
      its atmosphere since 2003. The contribution of possible sources of primary PM2.5
      and its precursors is not known. In this paper we present the results of
      analyzing the chemical composition of sixty 24-hr samples of PM2.5 to determine
      possible sources of PM2.5 in the MMA. The samples were collected at the northeast
      and southeast of the MMA between November 22 and December 12, 2007, using low
      volume devices. Teflon and quartz filters were used to collect the samples. The
      concentrations of 16 airborne trace elements were determined using x-ray
      fluorescence (XRF). Anions and cations were determined using ion chromatography.
      Organic carbon (OC) and elemental carbon (EC) were determined by thermal optical
      analysis. The results show that Ca had the maximum mean concentration of all
      elements studied, followed by S. Enrichment factors above 50 were calculated for
      S, Cl, Cu, Zn, Br and Pb. This indicates that these elements may come from
      anthropogenic sources. Overall, the major average components of PM2.5 were OC
      (41.7%), SO4(2-) (22.9%), EC (7.4%), crustal material (11.4%), and NO3- (12.6%),
      which altogether accounted for 96% of the mass. Statistically, we did not find
      any difference in SO4(2-) concentrations between the two sites. The fraction of
      secondary organic carbon was between 24% and 34%. The results of the factor
      analysis performed over 10 metals and OC and EC show that there are three main
      sources of PM2.5: crustal material and vehicle exhaust; industrial activity; and
      fuel oil burning. The results show that SO4(2-), OC, and crustal material are
      important components of PM2.5 in MMA. Further work is necessary to evaluate the
      proportion of secondary inorganic and organic aerosol in order to have a better
      understanding of the sources and precursors of aerosols in the MMA.

PMID- 22866584
TI  - A wind tunnel test of newly developed personal bioaerosol samplers.
AB  - In this study the performance of two newly developed personal bioaerosol samplers
      was evaluated. The two test samplers are cyclone-based personal samplers that
      incorporate a recirculating liquid film. The performance evaluations focused on
      the physical efficiencies that a personal bioaerosol sampler could provide,
      including aspiration, collection, and capture efficiencies. The evaluation tests
      were carried out in a wind tunnel, and the test personal samplers were mounted on
      the chest of a full-size manikin placed in the test chamber of the wind tunnel.
      Monodisperse fluorescent aerosols ranging from 0.5 to 20 microm were used to
      challenge the samplers. Two wind speeds of 0.5 and 2.0 m/sec were employed as the
      test wind speeds in this study. The test results indicated that the aspiration
      efficiency of the two test samplers closely agreed with the ACGIH inhalable
      convention within the size range of the test aerosols. The aspiration efficiency
      was found to be independent of the sampling orientation. The collection
      efficiency acquired from these two samplers showed that the 50% cutoff diameters
      were both around 0.6 microm. However the wall loss of these two test samplers
      increased as the aerosol size increased, and the wall loss of PAS-4 was
      considerably higher than that of PAS-5, especially in the aerosol size larger
      than 5 microm, which resulted in PAS-4 having a relatively lower capture
      efficiency than PAS-5. Overall, the PAS-5 is considered a better personal
      bioaerosol sampler than the PAS-4.

PMID- 22866585
TI  - Development of regenerative dye impregnated mesoporous silica materials for
      assessing exposure to ammonia.
AB  - The mesostructured materials MCM-41 and SBA-15 were studied as possible supports
      of bromocresol green (BG) dye impregnation for the ammonia gas detection because
      of their large surface area, high regenerative property, and high thermal
      stability. X-ray diffraction, transmission electron microscopy, scanning electron
      microscope, and N2 adsorption analysis were used to characterize the prepared
      materials. These materials could sense ammonia via visible color change from
      yellowish-orange to blue color. The color change process of the nanostructured
      materials was fully reversible during 10 cyclic tests. The results indicated that
      the ammonia absorption responses of the two nanostructured materials were both
      very sensitive, and high linear correlation and high precision were achieved. As
      the gaseous ammonia concentrations were 50 and 5 ppmv, the response times for the
      SBA-15/BG were only 1 and 5 min, respectively. Moreover the BG dye-impregnated
      SBA-15 was less affected by the variation in the relative humidity. It also had
      faster response for the detection of NH3, as well as lower manufacturing price as
      compared to that of the dye-impregnated MCM-41. Such feature enables SBA-15/BG to
      be a very promising material for the detection of ammonia gas.

PMID- 22866586
TI  - A study on the characteristics of silt loading on paved roads in the Seoul
      metropolitan area using a mobile monitoring system.
AB  - This study is considered the first attempt to apply a mobile monitoring system to
      estimating silt loading on paved roads in a megacity such as the Seoul
      metropolitan area. Using a mobile monitoring system developed in 2005, we
      estimated silt loadings on representative paved roads in the Seoul metropolitan
      area, including the city of Incheon, over a period of 3 yr. The temporal and
      spatial characteristics of silt loading were investigated for the carefully
      selected roads that may reflect the characteristics of the cities of Seoul and
      Incheon. In this study, changes in the average silt loading values were
      investigated in terms of land use, the temporal resolution of data acquisition
      (i.e., seasonal, daily, three-hour scale), the road width or number of lanes, and
      rainfall, which may affect the characteristics of the average silt loading
      significantly. It was found that the advantages of using the mobile monitoring
      system are its ability to obtain a large quantity of silt loading data in a short
      period of time and over a wide area and its ability to create a silt loading map
      showing the relative magnitude of silt loading in relation to a specific
      location, which makes it possible to easily locate hot spots.

PMID- 22866587
TI  - The new Fandangle.

PMID- 22866588
TI  - A qualitative investigation of specialist orthodontists in New Zealand. Part 1.
      Orthodontists and orthodontic practice.
AB  - BACKGROUND: Current knowledge of orthodontic practice is largely anecdotal and
      the lack of systematic knowledge can create barriers to better identifying the
      factors that make a successful orthodontist. The aim of this study was to
      investigate the routine practising lives of New Zealand orthodontists in order to
      generate an understanding of the reality of orthodontic specialist practice and
      its effects on their professional and personal lives. METHODS: Semi-structured
      interviews were conducted involving 19 practising orthodontists (four females, 15
      males; mean age 50 years) throughout New Zealand.Transcribed interviews were
      analysed for themes using an applied grounded theory approach. RESULTS: A core
      category of 'practising orthodontists' was derived, and related themes were
      grouped under the sub-categories of: (a) NZ orthodontic specialist practice; (b)
      NZ specialist orthodontists; and (c) work-life balance. The present paper reports
      on the first two subcategories. Themes elucidated under the specialist practice
      sub-category included modernisation, changing social norms, practice arrangement,
      branch practice, staffing, competition, legislation, advertising, the future and
      the provision of orthodontics by non-specialists. Themes in the orthodontic
      specialist sub-category were prior experience, postgraduate training, recent
      graduates, reasons for specialising, generational differences, females in
      orthodontics, NZ and overseas practice, the ageing profession and the prospect of
      an orthodontist shortage. CONCLUSIONS: This investigation has shed light on
      orthodontists and the practice of orthodontics in New Zealand and determined
      aspects rarely discussed in the current or previous literature. It will be
      valuable to observe how orthodontists and orthodontic practice continue to evolve
      in response to changes in NZ society.

PMID- 22866589
TI  - The safety zone for mini-implant maxillary anchorage in Mongoloids.
AB  - AIM: This study aimed to establish a safety zone for the placement of mini
      implants in the buccal surface between the second maxillary premolar (PM2) and
      first maxillary molar (M1) of Mongoloids. METHODS: Thirty-two digital
      orthopantomograms of Mongoloids were selected and the interdental distance
      between the second premolar and first molar at 2, 5, 8 and 11 mm from the cemento
      enamel junction (CEJ) was measured. The distance between the PM2 and M1 root
      apices and from the apices to the maxillary sinus was also determined. RESULTS:
      The average width (mm) at 2 mm was 2.58 +/- 0.53; 5 mm was 3.47 +/- 0.61; 8 mm
      was 4.00 +/- 0.74, 11 mm was 4.36 +/- 0.71 and the distance between the apices
      was 7.49 +/- 0.79. Only half of the samples were measured at 11 mm, as many of
      the root apices were superimposed over the maxillary sinus. The measurement (mm)
      from PM2 root apex to the sinus was -0.18 +/- 1.56, from the mesiobuccal root
      apex of M1 (MB1) to the sinus was -1.94 +/- 1.70 and from the midpoint between
      their apices to the sinus was -2.96 +/- 2.06 (superimposed on the sinus).
      CONCLUSION: The safest area to place mini-implants between the second premolar
      and the first molar in the maxilla of Mongoloids is between 5 to 8 mm above the
      CEJ.

PMID- 22866590
TI  - Validity and reliability of tooth size and dental arch measurements: a stereo
      photogrammetric study.
AB  - BACKGROUND: The development of three-dimensional computer imaging has many
      applications in dentistry, including the analysis of dental casts. AIMS: To
      assess the validity and reliability of a dental stereophotogrammetric imaging
      system. METHODS: The sample consisted of 35 sets of dental costs. Maxillary and
      mandibular dental crown widths and selected dental arch dimensions were measured
      directly using digital calipers. Cast images were also captured by a
      stereophotogrammetric system and analysed using Australis software. Dahlberg's
      formula, paired t-tests and intra-class correlations were used to assess the
      random error, validity and reliability of the measurements, respectively.
      RESULTS: Most values demonstrated no significant difference between the direct
      and three-dimensional measurements with mean differences ranging from 0.05-0.21
      mm. Moreover, values of intra-class correlation coefficients ranged between 0.80
      0.99 for intra-examiner reliability. CONCLUSIONS: Mesiodistal crown widths and
      dental arch dimensions may be measured accurately with relatively small error by
      the specially-designed 3D system and confirms its suitability for clinical and
      research purposes.

PMID- 22866591
TI  - A comparison of two orthodontic aesthetic indices.
AB  - OBJECTIVES: A cross-sectional study was conducted to determine the level of
      agreement between the Dental Aesthetic Index (DAI) and the Aesthetic Component
      (AC) of the Index of Orthodontic Treatment Need (IOTN). METHODS: DAI and AC
      scores were recorded in 728 subjects (340 females and 388 males, aged 11-20
      years). The percentage of subjects needing treatment and the different treatment
      categories for the DAI and AC were gender compared. Spearman's rank correlation
      coefficient (rho) was used to explore the relationship between the DAI and AC
      scores. Observer determined and Kappa statistics were used to analyse the
      diagnostic level of agreement between the DAI and AC, sorted into 'yes' or 'no'
      categories of orthodontic treatment need. RESULTS: According to the DAI and AC,
      21.8 and 10.9% of subjects were in need of treatment, respectively. Significant
      positive correlations existed between the DAI and AC scores (rho = 0.795). The
      DAI had a lower treatment need threshold compared with the AC. The Kappa
      statistics and percentage agreement between the DAI and AC was 0.55 (95% CI: 0.46
      0.63) and 87.6%, respectively. CONCLUSION: The DAI and AC showed strong
      association. However, only a moderate level of diagnostic agreement was
      identified (12.4% difference in observed percentage agreement) which highlights
      the need for a unified and universal orthodontic index for consideration when
      interpreting, comparing, or quantifying treatment needs.

PMID- 22866592
TI  - The effects of non-extraction orthodontic treatment on the vertical dimension: a
      comparison of a dolichofacial and a mesofacial group.
AB  - OBJECTIVE: The decision regarding extraction or non-extraction orthodontic
      treatment for patients with different skeletal facial patterns is more commonly
      based on traditional concepts rather than scientific facts. The present study
      aimed to investigate whether dolichofacial patients responded differently
      compared with mesofacial patients to non-extraction orthodontic treatment with
      respect to vertical changes in facial height. METHODS: Twenty-eight dolichofacial
      patients and 29 mesofacial patients who underwent non-extraction orthodontic
      treatment were selected. All patients commenced treatment prior to 15 years of
      age and had a mean age of 12.3 years for the dolichofacial group and 12.6 years
      for the mesofacial group. Serial lateral cephalometric radiographs were traced by
      hand on acetate paper and digitised using the Rocky Mountain Orthodontics JOE 32
      programme. Statistical analysis examined the recorded changes in facial axis
      angle, facial angle, menton-to-ANS distance and facial convexity. RESULTS: An
      increase in menton-to-ANS distance and facial angle and a decrease in facial
      convexity were observed in both groups to a similar extent. Interestingly, the
      facial axis of both groups remained constant throughout treatment and up to two
      years post-treatment. Both groups showed slightly increased facial axis angle
      beyond the original value at two years post-treatment. No statistically
      significant difference between the two groups was observed in the changes of any
      of the variables over time. CONCLUSION: The results countered the traditional
      concept that dolichofacial patients would have an increased facial height after
      being subjected to non-extraction orthodontic mechanics. It appeared that long
      term vertical height of the face was more dependent on genetics rather than
      environmental influences.

PMID- 22866593
TI  - The effect of changing crosshead speed on the shear bond strength of orthodontic
      bonding adhesive.
AB  - OBJECTIVE: To examine the influence of different crosshead speeds on the in vitro
      shear bond strength and adhesive remnant index scores for the same orthodontic
      adhesive. MATERIALS AND METHODS: One hundred human molars were randomly allocated
      to four groups. Brackets (.022 inch Victory series, 3M, Monrovia, CA, USA) were
      bonded with Ortho Solo primer (Ormco, Glendora, CA, USA) and Enlight (Ormco,
      Glendora, CA, USA) adhesive paste to their buccal surfaces. The brackets were
      debonded with a universal testing machine (Instron, Canton, MA, USA) with each
      group subjected to a different crosshead speed of 0.5 mm/min, 1.0 mm/min, 2.0
      mm/min and 5.0 mm/minute. Shear bond strength (SBS) was measured and enamel
      surfaces were examined to determine the adhesive remnant index (ARI) score.
      RESULTS: No significant differences were found between the mean SBS or ARI score
      for any of the groups. CONCLUSIONS: Studies using different crosshead speeds when
      testing identical adhesives may be used to compare the SBS of other orthodontic
      adhesives, provided the testing protocols are similar.

PMID- 22866594
TI  - Risk factors associated with external apical root resorption of the maxillary
      incisors: a 15-year retrospective study.
AB  - AIM: To determine the possible risk factors for external apical resorption (EARR)
      of the maxillary incisors. METHODS: Panoramic radiographs of 132 orthodontic
      patients with a mean age of 16.9 +/- 3.6 years were selected from two practice
      centres in Tehran. The radiographs were taken between 1990 and 2005 and 63.6% of
      the subjects were female. Mean, standard deviation and distribution of EARR for
      various variables were assessed. Prevalence significance, as well as differences
      between frequency distributions of clinical EARR (> or = 1.2 mm) between genders,
      treatment plans (extraction/ non-extraction), initial overjet and overbite
      magnitude, and incisor types (centrals/laterals) were evaluated by the chi
      squared test. The mean resorption rates on central and lateral incisors were
      compared using the independent-samples t-test. Associations between EARR with the
      age, duration of treatment, pretreatment overjet and overbite were assessed by
      the Pearson's correlation test. The reliability of the method was determined by
      remeasuring 117 randomly selected incisors and determining the associations
      between both sets of measurements with the Pearson's correlation coefficients.
      RESULTS: The prevalence of EARR, and clinical EARR (> or = 1.2 mm) were 91.8% and
      44.78% respectively. The average of EARR was 1.377 +/- 1.214 mm, or 8.65 +/-
      8.021% of pretreatment root lengths. The prevalence of clinical EARR was
      significantly higher in extraction cases, cases with greater initial overjet and
      on lateral incisors. Using the t-test, significant differences (p < 0.05) were
      observed between the extent of resorption between genders (higher in females),
      treatment plans (higher in extraction cases) and incisor types (greater on
      lateral incisors). Longer treatment times and excessive initial overjet were
      correlated with higher EARR levels (p < 0.05, r < 0.2). CONCLUSIONS: Factors
      related to premolar extraction, initial ovejet size, treatment time and being
      female may be correlated with higher EARR. Clinically significant resorption did
      not occur more in females.

PMID- 22866595
TI  - Association between maxillary canine impaction and arch dimensions.
AB  - OBJECTIVE: To compare palatal height index, arch width, and arch length
      characteristics in Iranian patients presenting with palatal and buccal canine
      impaction with a matched control group. MATERIALS AND METHODS: The casecontrol
      study examined 53 patients with canine impaction. The subjects were divided into
      two groups determined by buccal or palatal impaction which were compared with 53
      control subjects presenting without impaction. Subjects in the experimental
      groups were matched with individuals in the control group according to age,
      gender, crowding and type of malocclusion. Palatal height and arch length were
      measured with a Korkhaus three-dimensional divider. Arch width was determined in
      the anterior and posterior portions of the maxillary arch with a digital caliper.
      Data were compared with paired t-tests. RESULTS: The buccal canine impaction
      group exhibited mean differences in arch length between the case and control
      groups of 0.8 mm (SD 1.63, p = 0.041). The differences between the case and
      control groups in intermolar width, interpremolar width, intercanine width,
      palatal depth, and palatal height index were not statistically significant. The
      palatal impaction group showed no statistically significant differences between
      the case and control group in any of the dependent variables (p < or = 0.05). In
      a retest examination of arch dimensions, Bland-Altman plots showed no differences
      between the first and second measurements. CONCLUSIONS: Arch length in the buccal
      canine group was the only statistically significant variable. The difference was
      small and was considered not clinically significant.

PMID- 22866596
TI  - The effects of face mask therapy with and without rapid maxillary expansion in
      adolescent patients.
AB  - OBJECTIVE: To examine the effects of face mask therapy with and without
      associated rapid maxillary expansion (RME) in adolescent patients presenting with
      skeletal Class III malocclusion characterised by maxillary retrognathism.
      METHODS: Case records consisting of lateral cephalograms and hand-wrist films of
      43 patients with hypoplastic maxillary Class III malocclusions treated using a
      face mask with and without an RME were analysed. The patients were divided into
      two groups; Group A (N = 27) were treated with a face mask coupled with rapid
      maxillary expansion and patients in Group B (N = 16) were treated with a face
      mask appliance only. Ten cephalometric linear and 9 angular variables were
      measured to assess the dentofacial changes. Within group and between groups
      comparisons were determined by a paired t-test and Student's t-test,
      respectively. RESULTS: Forward displacement of the maxilla and a clockwise
      rotation of the mandible occurred in both groups. The maxillary-mandibular
      relationship improved and soft-tissue changes resulted in a more convex profile.
      The maxillary incisors moved forward only in Group B subjects but the mandibular
      incisors moved backward in both groups. CONCLUSIONS: Face mask therapy with and
      without an associated RME improved skeletal Class III malocclusion by a
      combination of skeletal and dental changes. These results suggested that the use
      of an RME should be based on clinical criteria rather than assisting the Class
      III correction.

PMID- 22866597
TI  - The effect of fluoride exposure on the load-deflection properties of superelastic
      nickel-titanium-based orthodontic archwires.
AB  - BACKGROUND: It has been demonstrated that fluoride prophylactic agents may cause
      hydrogen absorption in NiTi wires and degrade their mechanical properties. AIMS:
      To investigate the effect of a fluoride mouthwash on load-deflection
      characteristics of three types of nickel-titanium-based orthodontic archwires.
      METHODS: Twenty maxillary 0.016 inch round specimens from each of the single
      strand NiTi (Rematitan 'Lite'), multi-strand NiTi (SPEED Supercable) and Copper
      NiTi (Damon Copper NiTi) wires were selected. The specimens were kept in either
      0.2% NaF or artificial saliva solutions at 37 degrees C for 24 hours (N = 10).
      The wire load-deflection properties were measured by a Zwick testing machine,
      using a three-point bending test. An un-paired student's t-test, a one-way ANOVA
      and a Tukey post-hoc test were used to assess statistical significance. RESULTS:
      Immersion in NaF solution affected the load-deflection properties of NiTi wires.
      The unloading forces at 0.5 and 1.0 mm deflections were significantly lower in
      fluoride-treated specimens compared with the control groups (p < 0.05). Unloading
      forces at 1.5, 2.0 and 2.5 mm deflections were not statistically different
      between fluoride- and saliva-treated specimens (p > 0.05). CONCLUSIONS: The
      results suggested that subjecting NiTi wires to fluoride agents decreased
      associated unloading forces, especially at lower deflections, and may result in
      delayed tooth alignment.

PMID- 22866598
TI  - Orthodontic treatment of a patient with unerupted maxillary central and lateral
      incisors and canine: a case report.
AB  - AIM: The aim of this case report was to describe the orthodontic and periodontal
      management of a patient with three impacted anterior teeth. METHODS: An 18-year
      old female with Class I crowding on a Class I skeletal base presented with the
      chief complaint of an unaesthetic smile. Clinical examination revealed an
      impacted upper right permanent canine (13), lateral (12) and central incisor
      (11), a retained deciduous incisor and moderate crowding in the lower arch. The
      impacted teeth were surgically exposed (closed exposure) and aligned with fixed
      appliances. The 12 was extracted due to root resorption and 44 extracted to
      resolve the lower arch crowding. A fraenectomy and gingival recontouring were
      required. RESULTS: Orthodontic treatment resulted in improved overjet, overbite
      and an acceptable facial profile. The patient reported improved self esteem.
      CONCLUSIONS: While impacted anterior teeth are a clinical challenge, their
      surgical exposure, in combination with fixed appliances, is a conservative
      treatment plan which is not without complications.

PMID- 22866599
TI  - Hemimandibular hyperplasia: a rare case of vertical facial asymmetry. A case
      report.
AB  - BACKGROUND: Hemimandibular hyperplasia (HH), also known as hemimandibular
      hypertrophy, is characterised by excessive unilateral three-dimensional growth of
      the mandible after birth. Vertical elongation of the mandible on one side becomes
      clinically evident as a rare form of vertical facial asymmetry. Aberrant growth
      of the facial skeleton affects the developing dentition and dental compensation
      is usually unable to maintain optimal occlusal relationships. The resulting
      malocclusion is best managed surgically to address the various facial, skeletal
      and dental problems that confront clinicians. AIM: To present a case of
      hemimandibular hyperplasia treated using a combined surgical-orthodontic
      approach. METHODS: Combined surgical-orthodontic treatment was accomplished in
      four phases: 1) presurgical orthodontic, 2) surgical, 3) post-surgical
      orthodontic and 4) orthodontic retention. Comprehensive records (including
      photographs, study models and radiographs) were taken at the pre-treatment, pre
      surgery and debanding stages of treatment. RESULTS: A significant improvement in
      facial symmetry and a positive occlusal outcome were achieved. A more balanced
      gingival display has improved the patient's smile aesthetics. CONCLUSION:
      Hemimandibular hyperplasia is a rare condition causing vertical facial asymmetry
      and a resulting malocclusion. A combined surgical-orthodontic approach is able to
      accomplish sound facial, skeletal and dental treatment outcomes.

PMID- 22866600
TI  - A severe open bite case treated with orthodontics and tongue reduction surgery:
      13-year followup. A case report.
AB  - BACKGROUND: The management of open bite malocclusions creates controversy when
      treatment approach and long-term stability are considered. Tongue size, posture
      and habits have been associated as aetiologic and compounding factors. Reduction
      tongue surgery has therefore been advocated as an aid in treatment, especially
      when the open bite is accompanied by perceived macroglossia. AIM: The present
      article describes a clinical case of a 10-year-old girl who started treatment in
      the mixed dentition with an excessive open bite and speech defects. METHODS: A
      combination of orthodontics and a partial glossectomy was necessary to
      successfully address the open bite associated with an enlarged tongue. RESULTS:
      The need for orthognathic surgery treatment was eliminated and the patient was
      satisfied with the post-treatment aesthetics, function and speech. CONCLUSION:
      After 13 years of follow-up, a stable occlusion was maintained with only minor
      relapse.

PMID- 22866601
TI  - Cleanliness is next to godliness.

PMID- 22866602
TI  - Synthesis of phenols via fluoride-free oxidation of arylsilanes and
      arylmethoxysilanes.
AB  - Rapid, efficient methods have been developed to prepare phenols from the
      oxidation of arylhydrosilanes. The effects of arene substituents and fluoride
      promoters on this process show that while electron-deficient arenes can undergo
      direct oxidation from the hydrosilane, electron-rich aromatics benefit from
      silane activation via oxidation to the methoxysilane using homogeneous or
      heterogeneous transition metal catalysis. The combination of these two oxidations
      into a streamlined flow procedure involving minimal processing of reaction
      intermediates is also reported.

PMID- 22866603
TI  - Picosecond spectral relaxation of curcumin excited state in a binary solvent
      mixture of toluene and methanol.
AB  - Picosecond spectral relaxation of the excited state of curcumin in a binary
      solvent mixture of toluene and MeOH (or MeOH-d4) is reported with an instrument
      time resolution of ~40 ps. With increasing mole fraction of MeOH (MeOH-d4) the
      fluorescence intensity and lifetime of curcumin increase to a maximum at a MeOH
      (MeOH-d4) mole fraction of 0.14 (0.40) and then decrease. In addition,
      fluorescence decays taken at the red edge of the emission spectrum started to
      show measurable rise times (170 to 30 ps), the magnitude of which decreased
      gradually with increasing alcohol mole fraction. This is attributed to the
      modulation of the nonradiative rates associated with the excited-state
      intermolecular H(D) bonding between the pigment and the polar protic solvent. As
      a consequence, the solvation times in the binary mixture were observed to slow
      down considerably (20-40 times) at certain solvent compositions compared to neat
      MeOH. The fact that three Gaussian components are needed to adequately represent
      the steady-state emission spectra and two isosbestic points are observed in the
      time-resolved area normalized emission (TRANE) spectra of the pigment suggests
      the existence of at least three species in the excited state. The observed
      results are rationalized with a scheme where ground state of the pigment exists
      in free and H-bonded (intermolecular) state. Optical excitation results in a
      mixture of these species in the excited state and the observed spectral
      relaxation correspond to the conversion of these two species in to a third
      species where dipolar solvation and intermolecular H-bonding have been optimized.

PMID- 22866604
TI  - A concise synthesis of (+)-artemisinin.
AB  - Malaria represents one of the most medically and economically debilitating
      diseases present in the world today. Fortunately, there exists a highly effective
      treatment based on the natural product artemisinin. Despite the development of
      several synthetic approaches to the natural product, a streamlined synthesis that
      utilizes low-cost chemical inputs has yet to materialize. Here we report an
      efficient, cost-effective approach to artemisinin. Key to the success of the
      strategy was the development of mild, complexity-building reaction cascades that
      allowed the use of readily available, affordable cyclohexenone as the key
      starting material.

PMID- 22866605
TI  - The regulatory challenge of food allergens.
AB  - Food allergy is an important public health issue worldwide. Allergic consumers
      must avoid eating foods that could provoke potentially life-threatening
      reactions, and successful avoidance depends on having complete and accurate
      information on food labels. Regulatory agencies support allergic consumers by
      working with industry to ensure that all food allergens that are intended to be
      present in a food are declared on the label and that effective controls are used
      to prevent the presence of unintended allergens. These regulatory activities take
      place in a complex legal and policy environment both domestically and
      internationally. Protecting allergic consumers in this complex environment
      requires effective use of public health data and risk assessments. 

PMID- 22866606
TI  - Completeness of the disease recording systems for dairy cows in Denmark, Finland,
      Norway and Sweden with special reference to clinical mastitis.
AB  - BACKGROUND: In the Nordic countries Denmark, Finland, Norway and Sweden, the
      majority of dairy herds are covered by disease recording systems, in general
      based on veterinary registration of diagnoses and treatments. Disease data are
      submitted to the national cattle databases where they are combined with, e.g.,
      production data at cow level, and used for breeding programmes, advisory work and
      herd health management. Previous studies have raised questions about the quality
      of the disease data. The main aim of this study was to examine the country
      specific completeness of the disease data, regarding clinical mastitis (CM)
      diagnosis, in each of the national cattle databases. A second aim was to estimate
      country-specific CM incidence rates (IRs). RESULTS: Over 4 months in 2008,
      farmers in the four Nordic countries recorded clinical diseases in their dairy
      cows. Their registrations were matched to registrations in the central cattle
      databases. The country-specific completeness of disease registrations was
      calculated as the proportion of farmer-recorded cases that could be found in the
      central database. The completeness (95% confidence interval) for veterinary
      supervised cases of CM was 0.94 (0.92, 0.97), 0.56 (0.48, 0.64), 0.82 (0.75,
      0.90) and 0.78 (0.70, 0.85) in Denmark, Finland, Norway and Sweden, respectively.
      The completeness of registration of all CM cases, which includes all cases noted
      by farmers, regardless of whether the cows were seen or treated by a veterinarian
      or not, was 0.90 (0.87, 0.93), 0.51 (0.43, 0.59), 0.75 (0.67, 0.83) and 0.67
      (0.60, 0.75), respectively, in the same countries. The IRs, estimated by Poisson
      regression in cases per 100 cow-years, based on the farmers' recordings, were
      46.9 (41.7, 52.7), 38.6 (34.2, 43.5), 31.3 (27.2, 35.9) and 26.2 (23.2, 26.9),
      respectively, which was between 20% (DK) and 100% (FI) higher than the IRs based
      on recordings in the central cattle databases. CONCLUSIONS: The completeness for
      veterinary-supervised cases of CM was considerably less than 100% in all four
      Nordic countries and differed between countries. Hence, the number of CM cases in
      dairy cows is underestimated. This has an impact on all areas where the disease
      data are used.

PMID- 22866662
TI  - Bayesian structured additive regression modeling of epidemic data: application to
      cholera.
AB  - BACKGROUND: A significant interest in spatial epidemiology lies in identifying
      associated risk factors which enhances the risk of infection. Most studies,
      however, make no, or limited use of the spatial structure of the data, as well as
      possible nonlinear effects of the risk factors. METHODS: We develop a Bayesian
      Structured Additive Regression model for cholera epidemic data. Model estimation
      and inference is based on fully Bayesian approach via Markov Chain Monte Carlo
      (MCMC) simulations. The model is applied to cholera epidemic data in the Kumasi
      Metropolis, Ghana. Proximity to refuse dumps, density of refuse dumps, and
      proximity to potential cholera reservoirs were modeled as continuous functions;
      presence of slum settlers and population density were modeled as fixed effects,
      whereas spatial references to the communities were modeled as structured and
      unstructured spatial effects. RESULTS: We observe that the risk of cholera is
      associated with slum settlements and high population density. The risk of cholera
      is equal and lower for communities with fewer refuse dumps, but variable and
      higher for communities with more refuse dumps. The risk is also lower for
      communities distant from refuse dumps and potential cholera reservoirs. The
      results also indicate distinct spatial variation in the risk of cholera
      infection. CONCLUSION: The study highlights the usefulness of Bayesian semi
      parametric regression model analyzing public health data. These findings could
      serve as novel information to help health planners and policy makers in making
      effective decisions to control or prevent cholera epidemics.

PMID- 22866663
TI  - Selective targeting of the repressive transcription factors YY1 and cMyc to
      disrupt quiescent human immunodeficiency viruses.
AB  - Quiescent HIV-1 infection of resting CD4(+) T cells is an obstacle to eradication
      of HIV-1 infection. These reservoirs are maintained, in part, by repressive
      complexes that bind to the HIV-1 long terminal repeat (LTR) and recruit histone
      deacetylases (HDACs). cMyc and YY1 are two transcription factors that are
      recruited as part of well-described, distinct complexes to the HIV-1 LTR and in
      turn recruit HDACs. In prior studies, depletion of single factors that recruit
      HDAC1 in various cell lines was sufficient to upregulate LTR activity. We used
      short hairpin RNAs (shRNAs) to test the effect of targeted disruption of a single
      transcription factor on quiescent proviruses in T cell lines. In this study, we
      found that depletion of YY1 significantly increases mRNA and protein expression
      from the HIV-1 promoter in some contexts, but does not affect HDAC1, HDAC2,
      HDAC3, or acetylated histone 3 occupancy of the HIV-1 LTR. Conversely, depletion
      of cMyc or cMyc and YY1 does not significantly alter the level of transcription
      from the LTR or affect recruitment of HDACs to the HIV-1 LTR. Furthermore, global
      inhibition of HDACs with the HDAC inhibitor suberoylanilide hydroxamic acid
      (SAHA) enhanced the increase in LTR transcription in cells that were depleted of
      YY1.These findings show that despite prior isolated findings, redundancy in
      repressors of HIV-1 LTR expression will require selective targeting of multiple
      restrictive mechanisms to comprehensively induce the escape of quiescent
      proviruses from latency.

PMID- 22866664
TI  - Assessing therapeutic effectiveness of scalp treatments for dandruff and
      seborrheic dermatitis, part 2: the impact of gender and ethnicity on efficacy.
AB  - BACKGROUND: Dandruff and seborrheic dermatitis (D/SD) are common and troublesome
      scalp conditions that affect individuals independent of gender or ethnicity. AIM:
      To evaluate whether population gender or ethnic origins impact the magnitude of
      anti-dandruff therapeutic benefit obtained from use of a potentiated zinc
      pyrithione shampoo treatment. METHODS: A retrospective evaluation of anti
      dandruff clinical data covering a single-product technology was conducted to
      assess whether statistically meaningful differences were observed for gender or
      ethnic sub-populations. An analysis of covariance was performed on the pooled
      subject-level data. RESULTS: Meta-analysis of clinical data involving 1114
      subjects from seven trials demonstrated the lack of statistically significant
      impact of gender on flaking or selected biomarker measures. Similarly, a smaller
      population chosen to assess ethnicity demonstrated the lack of differences
      between Asian and Caucasian clinical sub-population responses (flaking severity).
      CONCLUSION: Through the use of both expert symptom grading and objective
      biomarker assessments, therapeutic efficacy of a potentiated zinc pyrithione
      shampoo was found to be independent of gender and ethnicity, being consistent
      with the lack of functional differences in skin from these populations.

PMID- 22866665
TI  - Inferior vena cava displacement during respirophasic ultrasound imaging.
AB  - BACKGROUND: Ultrasound measurement of dynamic changes in inferior vena cava (IVC)
      diameter can be used to assess intravascular volume status in critically ill
      patients, but published studies vary in accuracy as well as recommended
      diagnostic cutoffs. Part of this variability may be related to movements of the
      vessel relative to the transducer during the respiratory cycle which results in
      unintended comparison of different points of the IVC at end expiration and
      inspiration, possibly introducing error related to variations in normal anatomy.
      The objective of this study was to quantify both craniocaudal and mediolateral
      movements of the IVC as well as the vessel's axis of collapse during
      respirophasic ultrasound imaging. METHODS: Patients were enrolled from a single
      urban academic emergency department with ultrasound examinations performed by
      sonographers experienced in IVC ultrasound. The IVC was imaged from the level of
      the diaphragm along its entire course to its bifurcation with diameter
      measurements and respiratory collapse measured at a single point inferior to the
      confluence of the hepatic veins. While imaging the vessel in its long axis,
      movement in a craniocaudal direction during respiration was measured by tracking
      the movement of a fixed point across the field of view. Likewise, imaging the
      short axis of the IVC allowed for measurement of mediolateral displacement as
      well as the vessel's angle of collapse relative to vertical. RESULTS: Seventy
      patients were enrolled over a 6-month period. The average diameter of the IVC was
      13.8 mm (95% CI 8.41 to 19.2 mm), with a mean respiratory collapse of 34.8% (95%
      CI 19.5% to 50.2%). Movement of the vessel relative to the transducer occurred in
      both mediolateral and craniocaudal directions. Movement was greater in the
      craniocaudal direction at 21.7 mm compared to the mediolateral movement at 3.9 mm
      (p < 0.001). Angle of collapse assessed in the transverse plane averaged 115
      degrees  (95% CI 112 degrees  to 118 degrees ). CONCLUSIONS: Movement of the IVC
      occurs in both mediolateral and craniocaudal directions during respirophasic
      ultrasound imaging. Further, collapse of the vessel occurs not at true vertical
      (90 degrees ) but 25 degrees  off this axis. Technical approach to IVC assessment
      needs to be tailored to account for these factors.

PMID- 22866666
TI  - Robust polyfunctional T-helper 1 responses to multiple fungal antigens from a
      cell population generated using an environmental strain of Aspergillus fumigatus.
AB  - BACKGROUND AND AIMS: Aspergillus fumigatus infections are the leading cause of
      invasive fungal infection-related deaths in stem cell transplant patients, and
      may be amenable to correction with adoptive immunotherapy providing T lymphocytes
      specific for A. fumigatus. However, a clinically usable source of antigen and a
      reliable procedure for the generation of large numbers of Aspergillus-specific T
      lymphocytes to clinical-grade standards is not available. METHODS: An
      environmental strain of A. fumigatus (WMAfES) was isolated and cultured using
      materials and reagents suitable for clinical manufacture. Water-soluble lysate
      from germinated conidia of WMAfES was used as the antigen source. Peripheral
      blood mononuclear cells were stimulated with antigen-pulsed autologous dendritic
      cells on days 0 and 7. Cells were expanded with a cocktail of interleukin (IL)-2,
      IL-7 and IL-15 from days 7 to 21. RESULTS: We obtained a mean 32.8-fold increase
      in cell numbers over 21 days of culture (n = 8). Resultant cultures were
      predominantly effector and central memory CD4(+) T cells, which produced T-helper
      (h)1 and Th17 cytokines when restimulated with A. fumigatus antigen derived from
      environmental or clinically isolated A. fumigatus. Cultured cells exhibited a
      high level of specific expansion and chemokine production when restimulated.
      Moreover, cultured cells cross-reacted with antigens from other fungi, including
      Penicillium, Candida albicans and other non-fumigatus Aspergillus species.
      CONCLUSIONS: We describe a simple, robust, reproducible and clinically applicable
      procedure using a clinically appropriate antigen preparation for the expansion of
      polyfunctional A. fumigatus-specific T cells from normal donors of varying HLA
      types.

PMID- 22866667
TI  - Enhanced thermostability of a Rhizopus chinensis lipase by in vivo recombination
      in Pichia pastoris.
AB  - BACKGROUND: Lipase from Rhizopus chinensis is a versatile biocatalyst for various
      bioconversions and has been expressed at high-level in Pichia pastoris. However,
      the use of R. chinensis lipase in industrial applications is restricted by its
      low thermostability. Directed evolution has been proven to be a powerful and
      efficient protein engineering tool for improvement of biocatalysts. The present
      work describes improvement of the thermostability of R. chinensis lipase by
      directed evolution using P. pastoris as the host. RESULTS: An efficient, fast and
      highly simplified method was developed to create a mutant gene library in P.
      pastoris based on in vivo recombination, whose recombination efficiency could
      reach 2.3 * 105/MUg DNA. The thermostability of r27RCL was improved significantly
      by two rounds of error-prone PCR and two rounds of DNA shuffling in P. pastoris.
      The S4-3 variant was found to be the most thermostable lipase, under the
      conditions tested. Compared with the parent, the optimum temperature of S4-3 was
      two degrees higher, Tm was 22 degrees higher and half-lives at 60 degrees C and
      65 degrees C were 46- and 23- times longer. Moreover, the catalytic efficiency
      kcat/Km of S4-3 was comparable to the parent. Stabilizing mutations probably
      increased thermostability by increasing the hydrophilicity and polarity of the
      protein surface and creating hydrophobic contacts inside the protein.
      CONCLUSIONS: P. pastoris was shown to be a valuable cell factory to improve
      thermostability of enzymes by directed evolution and it also could be used for
      improving other properties of enzymes. In this study, by using P. pastoris as a
      host to build mutant pool, we succeeded in obtaining a thermostable variant S4-3
      without compromising enzyme activity and making it a highly promising candidate
      for future applications at high temperatures.

PMID- 22866668
TI  - Pavlovian-to-instrumental transfer in cocaine seeking rats.
AB  - Drug-associated cues are believed to be important mediators of addiction and drug
      relapse. Although such cues may influence drug-seeking behavior through multiple
      routes, it is their putative incentive motivational properties-their ability to
      elicit "craving"-that interests many addiction researchers. The Pavlovian-to
      instrumental transfer paradigm is commonly used to assay cue-evoked incentive
      motivation in situations involving natural rewards, but has not been widely
      applied to the study of drug self-administration. We used this paradigm to
      determine whether cues paired with intravenous cocaine could promote performance
      of an independently trained task in which rats self-administered cocaine by
      completing a chain of two different lever press actions, a procedure used to
      parse behavior into cocaine seeking (first action) and cocaine taking (second
      action). Rats showed significant transfer, increasing task performance during
      cocaine-paired cues. This effect was observed for both seeking and taking
      actions, although a trend toward greater cocaine taking was observed, a result
      that is consistent with studies using natural rewards. Our results demonstrate
      that cocaine-paired cues can provoke the pursuit of cocaine through a Pavlovian
      motivational process. This phenomenon may provide a useful new tool for modeling
      drug relapse, particularly as a method for targeting the response-invigorating
      effects of stimulus-drug learning.

PMID- 22866669
TI  - Determination of the best method to estimate glomerular filtration rate from
      serum creatinine in adult patients with sickle cell disease: a prospective
      observational cohort study.
AB  - BACKGROUND: Sickle cell disease (SCD) leads to tissue hypoxia resulting in
      chronic organ dysfunction including SCD associated nephropathy. The goal of our
      study was to determine the best equation to estimate glomerular filtration rate
      (GFR) in SCD adult patients. METHODS: We conducted a prospective observational
      cohort study. Since 2007, all adult SCD patients in steady state, followed in two
      medical departments, have had their GFR measured using iohexol plasma clearance
      (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD
      EPI equations without adjustment for ethnicity were tested to estimate GFR from
      serum creatinine. Estimated GFRs were compared to measured GFRs according to the
      graphical Bland and Altman method. RESULTS: Sixty-four SCD patients (16 men,
      median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They
      were Sub-Saharan Africa and French West Indies natives and predominantly lean
      (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured
      GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary
      albumin/creatinine ratio was higher in patients with hyperfiltration than in
      patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p =
      0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest
      bias and the greatest precision. Differences between estimated GFRs using the CKP
      EPI equation and measured GFRs decreased with increasing GFR values, whereas it
      increased with the Cockcroft-Gault and MDRD-v4 equations. CONCLUSIONS: We confirm
      that SCD patients have a high rate of glomerular hyperfiltration, which is
      frequently associated with microalbuminuria or macroalbuminuria. In non-Afro
      American SCD patients, the best method for estimating GFR from serum creatinine
      is the CKD-EPI equation without adjustment for ethnicity. This equation is
      particularly accurate to estimate high GFR values, including glomerular
      hyperfiltration, and thus should be recommended to screen SCD adult patients at
      high risk for SCD nephropathy.

PMID- 22866670
TI  - Platelet-rich plasma (PRP): an adjuvant to hasten hamstring muscle recovery. A
      randomized controlled trial protocol (ISCRTN66528592).
AB  - BACKGROUND: Muscle injuries are one of the commonest injuries affecting athletes.
      It often leads to significant pain and disability causing loss of training and
      competition time. With current treatment, the duration to return-to-play ranges
      form six weeks to never, depending on injury severity. Recent researches have
      suggested that autologous platelet-rich plasma (PRP) injection into the injured
      site may hasten soft tissues healing. To-date, there has been no randomised
      clinical trials to evaluate the effects of PRP on muscle healing. The aim of this
      study is to examine the effects of autologous PRP on duration to return-to-play
      after muscle injury. METHODS AND DESIGN: A randomised, single blind controlled
      trial will be conducted. Twenty-eight patients aged 18 years and above with a
      recent grade-2 hamstring injury will be invited to take part. Participants will
      be randomised to receive either autologous PRP injection with rehabilitation
      programme, or rehabilitation programme only. Participants will be followed up at
      day three of study and then weekly for 16 weeks. At each follow up visit,
      participants will be assessed on readiness to return-to-play using a set of
      criteria. The primary end-point is when participants have fulfilled the return-to
      play criteria or end of 16 weeks.The main outcome measure of this study is the
      duration to return-to-play after injury. CONCLUSION: This study protocol proposes
      a rigorous and potential significant evaluation of PRP use for grade-2 hamstring
      injury. If proven effective such findings could be of great benefit for patients
      with similar injuries. TRIAL REGISTRATION: Current Controlled Trials
      ISCRTN66528592.

PMID- 22866671
TI  - Health-related quality of life in different clinical subgroups with typical AFL
      who have undergone cavo-tricuspid isthmus ablation.
AB  - BACKGROUND: To evaluate changes in health-related quality of life (HRQOL) in
      different sub-groups of a cohort of patients with typical atrial flutter (AFL)
      treated with cavotricuspid isthmus (CTI) radiofrequency catheter ablation.
      METHODS: 95 consecutive patients due to undergo CTI ablation were enrolled in a
      study involving their completion of two SF-36 HRQOL questionnaires, before
      ablation and at one-year follow-up. RESULTS: 88 of the initial 95 patients
      finished the study. Regardless of whether patients experienced atrial
      fibrillation (AF) during follow-up, a statistically significant improvement in
      HRQOL was observed, compared with pre-ablation scores and in all dimensions
      except Bodily Pain. However, patients without AF during follow-up had
      significantly higher absolute HRQOL scores in most dimensions. No differences
      were seen in most HRQOL dimensions, with respect to AFL type (paroxysmal,
      persistent) or duration, whether AFL was first-episode or recurrent, Class I-III
      drug dependent, sex, or presence of structural heart disease or
      tachycardiomyopathy. Patients with persistent AFL showed the greatest improvement
      in HRQOL when they also had a ventricular cycle length <=500 ms. The combination
      of recurrent AFL, ventricular cycle length <=500 ms and structural heart disease
      led to a significantly greater improvement in physical HRQOL dimensions than did
      first-episode AFL, no structural heart disease and ventricular cycle >500 ms. The
      only independent factor associated with a greater improvement was structural
      cardiopathy. CONCLUSIONS: CTI-ablation treatment leads to a significant
      improvement in HRQOL in patients with typical AFL. Patients with AF during follow
      up show a significantly lower HRQOL at one-year post-ablation. The only
      independent risk factor found to be associated with a greater improvement in the
      physical summary component was structural cardiopathy.

PMID- 22866672
TI  - Indices used in differentiation of thalassemia trait from iron deficiency anemia
      in pediatric population: are they reliable?
AB  - BACKGROUND: Iron deficiency (IDA) and beta thalassemia trait (TT) are the most
      common causes of hypochromia and microcytosis. Many indices have been defined to
      quickly discriminate these similar entities via parameters obtained from
      automated blood cell analyzers. However, studies in the pediatric age group are
      scarce and their results are controversial. METHODS: We calculated eight
      discrimination indices [Mentzer Index (MI), England and Fraser Index (E&F),
      Srivastava Index (S), Green and King Index (G&K), Shine and Lal Index (S&L), red
      blood cell (RBC) count, RBC distribution width, and red blood cell distribution
      width Index (RDWI)] in 100 patients. We calculated sensitivity (SENS),
      specificity (SPEC), positive and negative predictive value (PPV and NPV), and
      Youden's Index (YI) of each discrimination index. RESULTS: None of the
      discrimination indices showed a SENS and SPEC of 100%. The highest SENS was
      obtained with S&L (87.1%), while the highest SPEC was obtained with E&F formula
      (100%). The highest YI value was obtained with E&F formula (58.1%). CONCLUSION:
      In our study, none of the formulas appears reliable in discriminating between TT
      and IDA patients. The evaluation of iron status and measurement of hemoglobin
      A(2) (HbA(2)) remain the most reliable investigations to differentiate between TT
      and IDA patients.

PMID- 22866673
TI  - Quantifying the PBAC in a pediatric and adolescent gynecology population.
AB  - STUDY OBJECTIVE: To determine the usefulness of the pictorial blood assessment
      chart (PBAC) for use as a valid screening tool for menorrhagia in adolescents.
      STUDY DESIGN: To conduct a prospective survey paired with retrospective chart
      review. MAIN OUTCOME MEASURES: To determine mean PBAC scores among adolescents
      presenting with menorrhagia versus normal or infrequent cycles. To determine the
      PBAC scores among adolescents self-identifying as having heavy, normal, or light
      menses. RESULTS: Seventy-three subjects met criteria. Teens self-identified as
      having "light," "medium," or "heavy" cycles. Groups were then subdivided: Group 1
      "heavy menses," Group 2 "normal menses," and Group 3 "light menses." The mean age
      of menarche was similar in all groups: 11.59 +/- 1.56 years, 11.41 +/- 1.51
      years, 11.78 +/- .83 years in Groups 1, 2, and 3, respectively. The mean PBAC
      score for the cohort was 195, while the mean PBAC in Group 1 was 362, compared to
      136 and 44 for Groups 2 and 3, respectively ( p < .002). CONCLUSIONS: This is the
      first study to address the use of the PBAC in an adolescent population. In
      addition, this study evaluates mean PBAC scores among teens who self-identify as
      having heavy, normal, or light periods. The incidence of bleeding disorders among
      those with menorrhagia was 20%, consistent with previously published studies.

PMID- 22866674
TI  - Risk of bleeding and inhibitor development after circumcision of previously
      untreated or minimally treated severe hemophilia A children.
AB  - BACKGROUND: Surgery and intensive factor VIII (FVIII) replacement may be risk
      factors for development of inhibitors. OBJECTIVE: To evaluate time and rate of
      inhibitor development postcircumcision over 12-month period, and to assess
      bleeding of children with severe hemophilia A after low-dose FVIII replacement
      and local hemostasis. PATIENTS AND METHODS: Sixty-one previously untreated
      patients (PUPs) or minimally treated patients (MTPs) with severe hemophilia A
      less than 36 months were enrolled; 25 underwent circumcision during the 18-month
      enrollment period, and 36 matched patients were not circumcised. All patients
      were treated on demand with plasma-derived FVIII, and all were inhibitor negative
      at the time of enrollment. Intron 22 inversion was analyzed. A potent hemostatic
      agent (gelatin sponge) was applied on the site of surgery, and then dressed with
      gauze. Two doses of FVIII concentrate (25 U/kg) were given, 1 hour before
      circumcision and 1 hour before removal of dressing. The inhibitor was determined
      every 8 exposure days (EDs). RESULTS: None of the patients had bleeding or
      infection, except one who had minimal transient bleeding 8 days after surgery,
      and was treated easily by a single dose of FVIII (50 U/kg). After a median of 16
      EDs, high-titer inhibitors developed in seven patients: three patients in the
      circumcised group (12%) in contrast to four patients (11.1%) in the
      noncircumcised group. CONCLUSION: Two doses factor concentrate and gelatin sponge
      application were generally enough to prevent bleeding after circumcision of
      severe hemophilia A. Circumcision and low-dose FVIII protocol were not an
      additional risk for development of high-titer inhibitor.

PMID- 22866675
TI  - Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after
      stroke: involvement of notch signalling.
AB  - Angiogenesis takes place after brain ischaemia, and stroke-induced angiogenesis
      in ischaemic brain may be associated with improved neurological recovery. Bone
      MSCs (marrow stromal cells) transplantation can promote this vital angiogenesis
      in ischaemic zones, but the mechanisms by which MSCs promoting angiogenesis are
      unclear. The Notch signalling pathway may play an important role in embryonic
      blood vessels development and tumour angiogenesis, but whether it is also
      involved in angiogenesis after cerebral ischaemia is uncertain. We therefore
      investigated the Notch signalling pathway in angiogenesis after stroke. Rats were
      subjected to MCAo (middle cerebral artery occlusion) and treated intravenously
      with or without MSCs at 24 h after injury. On day 1, 3 and 7 after treatment with
      MSCs or PBS, immunofluorescent staining, Western blot and RT-PCR (reverse
      transcription-PCR) assays were carried out to evaluate angiogenesis, and
      expression of VEGF (vascular endothelial growth factor) and Notch signals in the
      ischaemic cortex. Immunofluorescent showed a significant increase in both new
      microvessels, VEGF-positive cells and Notch1-positive microvessels in the
      ischaemic cortex in MSCs-treated group. RT-PCR indicated that MSC transplantation
      significantly raised VEGF mRNA and Hes1 mRNA levels in the ischaemic cortex. The
      data suggest that treatment with MSCs enhances stroke-induced angiogenesis in
      ischaemic brain, and that the Notch signalling pathway is involved.

PMID- 22866676
TI  - Awareness, perception and factors affecting utilization of cervical cancer
      screening services among women in Ibadan, Nigeria: a qualitative study.
AB  - BACKGROUND: Over the years awareness and uptake of cervical cancer screening
      services has remained poor in developing countries. Problems associated with
      cervical cancer incidence include late reporting, ignorance and cultural issues
      relating to cervical cancer screening. This study sought to explore the
      awareness, perception and utilization of cervical cancer screening among women in
      Ibadan as well as factors that influence utilization. METHOD: This is a
      qualitative study that utilized Eight Focus Group Discussions to collect
      information from women in selected health facilities in Ibadan, South West,
      Nigeria. The 82 participants were purposely recruited from women attending
      Antenatal clinics in 4 secondary and 4 primary health care facilities after
      approval was received from the Institutional Review Board in charge of the
      facilities. The focus group discussions were tape recorded and transcribed
      verbatim. The transcripts were analyzed into themes. FINDINGS: The study provided
      qualitative information on the awareness, perception of the utilization of
      cervical cancer screening services among women in Ibadan. Participants were
      mainly married women (92.7%), mean age =27.6, SD =4.5, mainly traders (39%) and
      from Yoruba ethnic backgrounds (87.8%) and had secondary education (39%). The
      respondents reported not being aware of cervical cancer and were not utilizing
      the services. Though they did not know what cervical cancer screening entailed or
      the screening methods, they still believed that it is important since like for
      other diseases will help in early detection and treatment. The participants were
      eager to get more information from nurses on cervical cancer about cervical
      cancer screening. The major factors identified by the women that influence
      screening utilization were ignorance, Illiteracy, belief in not being at risk,
      having many contending issues, nonchalant attitude to their health, financial
      constraint and fear of having a positive result. CONCLUSION: There is an urgent
      need for more enlightenment about cervical cancer especially by health workers.
      Also, cervical cancer services should be made available at very affordable cost
      so that women can easily access the services in order to reduce incidence of
      invasive cancer.

PMID- 22866678
TI  - Mind-sets matter: a meta-analytic review of implicit theories and self
      regulation.
AB  - This review builds on self-control theory (Carver & Scheier, 1998) to develop a
      theoretical framework for investigating associations of implicit theories with
      self-regulation. This framework conceptualizes self-regulation in terms of 3
      crucial processes: goal setting, goal operating, and goal monitoring. In this
      meta-analysis, we included articles that reported a quantifiable assessment of
      implicit theories and at least 1 self-regulatory process or outcome. With a
      random effects approach used, meta-analytic results (total unique N = 28,217; k =
      113) across diverse achievement domains (68% academic) and populations (age range
      = 5-42; 10 different nationalities; 58% from United States; 44% female)
      demonstrated that implicit theories predict distinct self-regulatory processes,
      which, in turn, predict goal achievement. Incremental theories, which, in
      contrast to entity theories, are characterized by the belief that human
      attributes are malleable rather than fixed, significantly predicted goal setting
      (performance goals, r = -.151; learning goals, r = .187), goal operating
      (helpless-oriented strategies, r = -.238; mastery-oriented strategies, r = .227),
      and goal monitoring (negative emotions, r = -.233; expectations, r = .157). The
      effects for goal setting and goal operating were stronger in the presence (vs.
      absence) of ego threats such as failure feedback. Discussion emphasizes how the
      present theoretical analysis merges an implicit theory perspective with self
      control theory to advance scholarship and unlock major new directions for basic
      and applied research.

PMID- 22866677
TI  - Influence of specific anions on the orientational ordering of thermotropic liquid
      crystals at aqueous interfaces.
AB  - We report that specific anions (of sodium salts) added to aqueous phases at molar
      concentrations can trigger rapid, orientational ordering transitions in water
      immiscible, thermotropic liquid crystals (LCs; e.g., nematic phase of 4'-pentyl-4
      cyanobiphenyl, 5CB) contacting the aqueous phases. Anions classified as
      chaotropic, specifically iodide, perchlorate, and thiocyanate, cause 5CB to
      undergo continuous, concentration-dependent transitions from planar to
      homeotropic (perpendicular) orientations at LC-aqueous interfaces within 20 s of
      addition of the anions. In contrast, anions classified as relatively more
      kosmotropic in nature (fluoride, sulfate, phosphate, acetate, chloride, nitrate,
      bromide, and chlorate) do not perturb the LC orientation from that observed
      without added salts (i.e., planar orientation). Surface pressure-area isotherms
      of Langmuir films of 5CB supported on aqueous salt solutions reveal ion-specific
      effects ranking in a manner similar to the LC ordering transitions. Specifically,
      chaotropic salts stabilized monolayers of 5CB to higher surface pressures and
      areal densities (12.6 mN/m at 27 A(2)/molecule for NaClO(4)) and thus smaller
      molecular tilt angles (30 degrees  from the surface normal for NaClO(4)) than
      kosmotropic salts (5.0 mN/m at 38 A(2)/molecule with a corresponding tilt angle
      of 53 degrees  for NaCl). These results and others reported herein suggest that
      anion-specific interactions with 5CB monolayers lead to bulk LC ordering
      transitions. Support for the proposition that these ion-specific interactions
      involve the nitrile group was obtained by using a second LC with nitrile groups
      (E7; ion-specific effects similar to 5CB were observed) and a third LC with
      fluorine-substituted aromatic groups (TL205; weak dipole and no ion-specific
      effects were measured). Finally, we also establish that anion-induced
      orientational transitions in micrometer-thick LC films involve a change in the
      easy axis of the LC. Overall, these results provide new insights into ionic
      phenomena occurring at LC-aqueous interfaces, and reveal that the long-range
      ordering of LC oils can amplify ion-specific interactions at these interfaces
      into macroscopic ordering transitions.

PMID- 22866679
TI  - Remembering kith and kin is underpinned by rapid memory updating: implications
      for exemplar theory.
AB  - The formation of stable social attachments requires that the specific physical
      characteristics of kith and kin are rapidly encoded, and that the resulting
      memories are updated when these characteristics gradually change. The idea that
      memories are updated in this way contrasts with influential exemplar models of
      memory, wherein each new pattern of characteristics should establish a new
      memory. Here, two experiments demonstrate a rapid form of memory updating in
      human face processing: An updated memory of a set of images of faces, varying in
      identity or age, is more likely to develop when these images from part of a
      gradually changing, rather than an abruptly changing, sequence or stream. These
      findings, while inconsistent with some exemplar theories, provide both a
      compelling demonstration of memory updating and insights into the nature of this
      process. They also represent a fresh impetus for theories wherein memory involves
      a process of evolution as opposed to mere replication of exemplars.

PMID- 22866680
TI  - A randomized trial of a classroom intervention to increase peers' social
      inclusion of children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Interventions for peer problems among children with attention
      deficit/hyperactivity disorder (ADHD) typically focus on improving these
      children's behaviors. This study tested the proposition that an adjunctive
      component encouraging the peer group to be socially inclusive of children with
      ADHD would augment the efficacy of traditional interventions. METHOD: Two
      interventions were compared: contingency management training (COMET), a
      traditional behavioral management treatment to improve socially competent
      behavior in children with ADHD, and Making Socially Accepting Inclusive
      Classrooms (MOSAIC), a novel treatment that supplemented behavioral management
      for children with ADHD with procedures training peers to be socially inclusive.
      Children ages 6.8-9.8 (24 with ADHD; 113 typically developing [TD]) attended a
      summer day program grouped into same-age, same-sex classrooms with previously
      unacquainted peers. Children with ADHD received both COMET and MOSAIC with a
      repeated measures crossover design. TD children provided sociometric information
      about the children with ADHD. RESULTS: Whereas the level of behavior problems
      displayed by children with ADHD did not differ across treatment conditions,
      children with ADHD displayed improved sociometric preference and more
      reciprocated friendships, and received more positive messages from peers, when
      they were in MOSAIC relative to COMET. However, the beneficial effects of MOSAIC
      over COMET predominantly occurred for boys relative to girls. CONCLUSIONS: Data
      support the concept that adjunctive procedures to increase the inclusiveness of
      the peer group may ameliorate peer problems among children with ADHD, and suggest
      the potential utility of modifying MOSAIC to be delivered in regular classroom
      settings.

PMID- 22866682
TI  - Communicating headings and preview sentences in text and speech.
AB  - Two experiments tested the effects of preview sentences and headings on the
      quality of college students' outlines of informational texts. Experiment 1 found
      that performance was much better in the preview sentences condition than in a no
      signals condition for both printed text and text-to-speech (TTS) audio rendering
      of the printed text. In contrast, performance in the headings condition was good
      for the printed text but poor for the auditory presentation because the TTS
      software failed to communicate nonverbal information carried by the visual
      headings. Experiment 2 compared outlining performance for five headings
      conditions during TTS presentation. Using a theoretical framework, "signaling
      available, relevant, accessible" (SARA) information, to provide an analysis of
      the information content of headings in the printed text, the manipulation of the
      headings systematically restored information that was omitted by the TTS
      application in Experiment 1. The result was that outlining performance improved
      to levels similar to the visual headings condition of Experiment 1. It is argued
      that SARA is a useful framework for guiding future development of TTS software
      for a wide variety of text signaling devices, not just headings.

PMID- 22866681
TI  - Longitudinal inspiratory capacity changes in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The changes in inspiratory capacity (IC) over time in chronic
      obstructive pulmonary disease (COPD) patients are unknown. The Understanding
      Potential Long-term Impacts on Function with Tiotropium (UPLIFT(r)) trial
      included IC measurements. METHODS: IC analysis from UPLIFT(r) (N = 5992) was
      performed at 1 and 6 months, and every 6 months through 4 years. Annualized rate
      of decline in pre- and post-bronchodilator IC and mean differences at each time
      point were analyzed by mixed-effects models. The relationships between baseline
      IC and exacerbation rate and mortality were explored using Cox regression
      analysis. RESULTS: Baseline characteristics: age, 65 years; 75% men; post
      bronchodilator forced expiratory volume in 1 second, 1.32 L (48% predicted); pre-
      and post-bronchodilator IC, 2.03 and 2.33 L. Mean IC rate of decline (mL/year)
      was 34 +/- 2 (1.7% of baseline) and 50 +/- 3 (2.1% of baseline) pre- and post
      bronchodilator, respectively, without significant between-group differences.
      Morning pre-bronchodilator (trough) IC improved with tiotropium versus placebo:
      124 mL (1 month), 103 mL (1 year), 107 mL (2 years), 98 mL (3 years), and 97 mL
      (4 years) (all p < 0.001). Post-bronchodilator improvements were similar between
      treatment groups. Lower baseline IC values were associated with reduced time to
      first exacerbation. For the lowest quartile (n = 1413) the values in months were
      14.3 (11.7-17.0) for tiotropium and 10.3 (8.8-11.7) for controls (p < 0.01).
      CONCLUSION: IC declines from approximately 34 to 50 mL/year in patients with
      stage II to IV COPD. Tiotropium treatment does not change the IC decline rate but
      provides 24-hour improvements in IC sustained over the long term. Trough IC
      differences suggest that tiotropium provides sustained decrease in end-expiratory
      lung volume.

PMID- 22866683
TI  - A route to well-being: intelligence versus wise reasoning.
AB  - Laypeople and many social scientists assume that superior reasoning abilities
      lead to greater well-being. However, previous research has been inconclusive.
      This may be because prior investigators used operationalizations of reasoning
      that favored analytic as opposed to wise thinking. We assessed wisdom in terms of
      the degree to which people use various pragmatic schemas to deal with social
      conflicts. With a random sample of Americans, we found that wise reasoning is
      associated with greater life satisfaction, less negative affect, better social
      relationships, less depressive rumination, more positive versus negative words
      used in speech, and greater longevity. The relationship between wise reasoning
      and well-being held even when controlling for socioeconomic factors, verbal
      abilities, and several personality traits. As in prior work, there was no
      association between intelligence and well-being. Further, wise reasoning mediated
      age-related differences in well-being, particularly among middle-aged and older
      adults. Implications for research on reasoning, well-being, and aging are
      discussed.

PMID- 22866685
TI  - Perceiving conspecifics as integrated body-gestalts is an embodied process.
AB  - We investigated the effect of posture congruence on social perception.
      Specifically, we tested the hypothesis that completing "body gestalts," rather
      than being a purely visual process, is mediated by congruence in the postures of
      observer and stimulus. We developed novel stimuli showing a face and 2 hands that
      could be combined in various ways to form "body gestalts" implying different
      postures. In 3 experiments we found that imitative finger movements were
      consistently faster when the observer's posture matched the posture implied by
      the configuration of face and hands shown onscreen, suggesting that participants
      intuitively used their own body schema to "fill in the gaps" in the stimuli.
      Besides shaping how humans perceive others' bodies, embodied body-gestalt (eBG)
      completion may be an essential social and survival mechanism, for example,
      allowing for quick recovery from deceptive actions. It may also partly explain
      why humans subconsciously align themselves in everyday interactions: This might
      facilitate optimal corepresentation at higher, conscious levels.

PMID- 22866684
TI  - The joint development of hemispheric lateralization for words and faces.
AB  - Consistent with long-standing findings from behavioral studies, neuroimaging
      investigations have identified a region of the inferior temporal cortex that, in
      adults, shows greater face selectivity in the right than left hemisphere and,
      conversely, a region that shows greater word selectivity in the left than right
      hemisphere. What has not been determined is how this pattern of mature
      hemispheric specialization emerges over the course of development. The present
      study examines the hemispheric superiority for faces and words in children, young
      adolescents and adults in a discrimination task in which stimuli are presented
      briefly in either hemifield. Whereas adults showed the expected left and right
      visual field superiority for face and word discrimination, respectively, the
      young adolescents demonstrated only the right-field superiority for words and no
      field superiority for faces. Although the children's overall accuracy was lower
      than that of the older groups, like the young adolescents, they exhibited a right
      visual field superiority for words but no field superiority for faces.
      Interestingly, the emergence of face lateralization was correlated with reading
      competence, measured on an independent standardized test, after regressing out
      age, quantitative reasoning scores, and face discrimination accuracy. Taken
      together, these findings suggest that the hemispheric organization of face and
      word recognition do not develop independently and that word lateralization, which
      emerges earlier, may drive later face lateralization. A theoretical account in
      which competition for visual representations unfolds over the course of
      development is proposed to account for the findings.

PMID- 22866686
TI  - Evidence against decay in verbal working memory.
AB  - The article tests the assumption that forgetting in working memory for verbal
      materials is caused by time-based decay, using the complex-span paradigm.
      Participants encoded 6 letters for serial recall; each letter was preceded and
      followed by a processing period comprising 4 trials of difficult visual search.
      Processing duration, during which memory could decay, was manipulated via search
      set size. This manipulation increased retention interval by up to 100% without
      having any effect on recall accuracy. This result held with and without
      articulatory suppression. Two experiments using a dual-task paradigm showed that
      the visual search process required central attention. Thus, even when memory
      maintenance by central attention and by articulatory rehearsal was prevented, a
      large delay had no effect on memory performance, contrary to the decay notion.
      Most previous experiments that manipulated the retention interval and the
      opportunity for maintenance processes in complex span have confounded these
      variables with time pressure during processing periods. Three further experiments
      identified time pressure as the variable that affected recall. We conclude that
      time-based decay does not contribute to the capacity limit of verbal working
      memory.

PMID- 22866687
TI  - Cognitive processes in associative and categorical priming: a diffusion model
      analysis.
AB  - Cognitive processes and mechanisms underlying different forms of priming were
      investigated using a diffusion model approach. In a series of 6 experiments,
      effects of prime-target associations and of a semantic and affective categorical
      match of prime and target were analyzed for different tasks. Significant
      associative and categorical priming effects were found in standard analyses of
      response times (RTs) and error frequencies. Results of diffusion model analyses
      revealed that priming effects of associated primes were mapped on the drift rate
      parameter (v), while priming effects of a categorical match on a task-relevant
      dimension were mapped on the extradecisional parameters (t0 and d). These results
      support a spreading activation account of associative priming and an explanation
      of categorical priming in terms of response competition. Implications for the
      interpretation of priming effects and the use of priming paradigms in cognitive
      psychology and social cognition are discussed. (PsycINFO Database Record (c) 2013
      APA, all rights reserved).

PMID- 22866688
TI  - Comparison of African American college students' coping with racially and
      nonracially stressful events.
AB  - Racial discrimination, a common experience for many African Americans, has been
      conceptualized within a stress and coping framework. However, few have examined
      whether racially stressful events are appraised and coped with differently from
      nonracially stressful events. The present study uses a daily diary method to
      examine African American college students' appraisals and coping behaviors in
      racially and nonracially stressful situations. The study examines the following 3
      questions: 1) Do African Americans appraise racially stressful events differently
      from nonracially stressful events? 2) Do they cope with racially stressful events
      differently from nonracially stressful events? and 3) Do they cope with racially
      stressful events differently from nonracially stressful events, even after
      controlling for differences in cognitive appraisals of the events? The present
      sample consists of 35 participants who reported experiencing at least one
      racially stressful event and at least one nonracially stressful event during a 20
      day diary study. Overall, no differences were found in students' appraisals in
      the racially stressful versus nonracially stressful events. Participants used
      less planful problem solving and more confrontive, ruminative, and avoidance
      coping strategies in the racially stressful events as compared with the
      nonracially stressful events. These findings suggest a need for race-specific
      models for coping with racial discrimination. (PsycINFO Database Record (c) 2012
      APA, all rights reserved).

PMID- 22866689
TI  - Racial identity and reasons for living in African American female suicide
      attempters.
AB  - The current study investigated the association between racial identity and
      reasons for living in African American women who have attempted suicide.
      Particular attention was paid to the relation between two elements of racial
      identity (private regard, racial centrality) and reasons for living, an
      alternative assessment of suicidal risk. While private regard refers to an
      individual's beliefs about the African American race, racial centrality describes
      the importance an individual places on his or her racial identity. The sample
      included 82 low-income African American women, ages 18-64, who reported a suicide
      attempt in the past 12 months. Participants, recruited from a large, urban public
      hospital located in the Southeast, completed the Reasons for Living Inventory and
      the Multidimensional Inventory of Black Identity, which included the private
      regard and racial centrality subscales. Results indicated that, as predicted,
      higher private regard was associated with more reasons for living. Contrary to
      expectations, racial centrality was not correlated with reasons for living nor
      was there an interaction between private regard and racial centrality indicating
      that racial centrality did not function as a moderator in predicting
      participants' reasons for living scores. Implications for culturally competent
      clinical interventions that target bolstering private regard are discussed.

PMID- 22866690
TI  - A development and validation of the Perceived Language Discrimination Scale.
AB  - This study was conducted to develop the Perceived Language Discrimination (PLD)
      scale across three samples of international students. In Sample 1 (N = 224), the
      seven items of the PLD were selected (alpha = .94) through an exploratory factor
      analysis. In Sample 2, a confirmatory factor analysis (N = 222) provided a cross
      validation of the one-factor model. Validity was supported by moderate positive
      associations of perceived language discrimination with depression (r = .35) and
      anxiety (r = .36), as well as small negative associations of perceived language
      discrimination with self-esteem (r = -.24) and life satisfaction (r = -.26).
      Moreover, perceived language discrimination had a large positive association with
      perceived racial discrimination (r = .62), a moderate negative association with
      perceived English proficiency (r = -.49), and a relatively weak association with
      social desirability (r = .14). Finally, perceived language discrimination added
      significant incremental variance in predicting depression and anxiety over and
      above perceived racial discrimination and perceived English proficiency,
      respectively. The results indicated measurement invariance and validity
      equivalency for the PLD between males and females as well as between the English
      and Non-English groups. In Sample 3, the estimated 2-week test-retest reliability
      (N = 31) was .83. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

PMID- 22866691
TI  - Implementation of a culturally adapted treatment to reduce barriers for Latino
      parents.
AB  - Literature to date has not yet included a comprehensive examination of barriers
      to participation in treatment for Latino populations, incorporating the role of
      acculturation. This study reports on the process of developing and implementing a
      culturally adapted treatment for promoting parent involvement by Latino parents
      in Head Start preschool programs and examines engagement factors affecting
      participation in the treatment. Results show that Latino parents with higher
      native cultural competence perceived more benefits to the treatment and reported
      fewer barriers than parents with lower native cultural competence. Also, the
      total number of barriers to participation that parents perceived before treatment
      was negatively associated with treatment participation, above and beyond the
      influence of acculturation factors, parent perceptions of economic stress, and
      perceived program benefits. Results are discussed in terms of how to establish
      effective community-based mental health and educational outreach programs to
      promote engagement with Latino families. The importance of using bidimensional
      models of acculturation within research designs with Latino populations and ideas
      for future research are discussed.

PMID- 22866692
TI  - Ethnic group moderates the association between attachment and well-being in later
      life.
AB  - Attachment styles are associated with well-being across the life span.
      Particularly in later life, when individuals face declining health and increasing
      dependency, patterns of attachment may relate to affective outcomes. However, few
      studies have empirically examined the attachment-well-being link at the end of
      the life span or considered whether ethnic group membership may moderate
      attachment-well-being links. Data from a sample of older adults (N = 1,116) were
      used to investigate how secure, dismissive, and fearful/avoidant styles predicted
      well-being in 4 ethnic groups; African Americans, European Americans, Eastern
      European immigrants, and English-speaking Caribbean immigrants. As expected, both
      secure and dismissive attachment dimensions were related to greater well-being,
      whereas fearful/avoidant attachment was associated with less. This positive
      impact of a secure attachment style of relating to others on well-being was
      stronger among African Americans and English-speaking Caribbeans compared with
      the European American and Eastern European immigrant groups. The negative impact
      of a fearful/avoidant attachment style of relating on well-being was buffered by
      being an English-speaking Caribbean but not for the other 3 groups. Results are
      interpreted in light of general and culture-specific premises of attachment. The
      article concludes with some implications and suggestions for future work.

PMID- 22866693
TI  - Comparing culturally accommodated versus standard group CBT for Latino
      adolescents with substance use disorders: a pilot study.
AB  - Studies comparing empirically supported substance abuse treatments versus their
      culturally accommodated counterparts with participants from a specific ethnic
      minority group are lacking in the literature. To address this gap, this pilot
      study was conducted to compare the feasibility and relative efficacy of an
      empirically supported standard version of cognitive-behavioral substance abuse
      treatment (S-CBT) to a culturally accommodated version (A-CBT) with a sample of
      Latino adolescents. This study was guided by a Cultural Accommodation Model for
      Substance Abuse Treatment (CAM-SAT). Thirty-five Latino adolescents (mean age =
      15.49) were randomly assigned to one of two 12-week group-based treatment
      conditions (S-CBT = 18; A-CBT = 17) with assessments conducted at pretreatment,
      posttreatment and 3-month follow-up. Results indicated similar retention and
      satisfaction rates for participants in both treatment conditions. In addition,
      participants in both conditions demonstrated significant decreases in substance
      use from pre- to posttreatment with slight increases at 3-month follow-up;
      however, substance use outcomes were moderated by two cultural variables: ethnic
      identity and familism. Implications of these findings within the context of
      conducting clinical trials with Latino adolescents are discussed. (PsycINFO
      Database Record (c) 2012 APA, all rights reserved).

PMID- 22866694
TI  - Synthesis and preclinical evaluation of QS-21 variants leading to simplified
      vaccine adjuvants and mechanistic probes.
AB  - QS-21 is a potent immunostimulatory saponin that is currently under clinical
      investigation as an adjuvant in various vaccines to treat infectious diseases,
      cancers, and cognitive disorders. Herein, we report the design, synthesis, and
      preclinical evaluation of simplified QS-21 congeners to define key structural
      features that are critical for adjuvant activity. Truncation of the linear
      tetrasaccharide domain revealed that a trisaccharide variant is equipotent to QS
      21, while the corresponding disaccharide and monosaccharide congeners are more
      toxic and less potent, respectively. Modification of the acyl chain domain in the
      trisaccharide series revealed that a terminal carboxylic acid is well-tolerated
      while a terminal amine results in reduced adjuvant activity. Acylation of the
      terminal amine can, in some cases, restore adjuvant activity and enables the
      synthesis of fluorescently labeled QS-21 variants. Cellular studies with these
      probes revealed that, contrary to conventional wisdom, the most highly adjuvant
      active of these fluorescently labeled saponins does not simply associate with the
      plasma membrane, but rather is internalized by dendritic cells.

PMID- 22866696
TI  - Effective cleaning of hexagonal boron nitride for graphene devices.
AB  - Hexagonal boron nitride (h-BN) films have attracted considerable interest as
      substrates for graphene. ( Dean, C. R. et al. Nat. Nanotechnol. 2010 , 5 , 722 -
      6 ; Wang, H. et al. Electron Device Lett. 2011 , 32 , 1209 - 1211 ; Sanchez
      Yamagishi, J. et al. Phys. Rev. Lett. 2012 , 108 , 1 - 5 .) We study the presence
      of organic contaminants introduced by standard lithography and substrate transfer
      processing on h-BN films exfoliated on silicon oxide substrates. Exposure to
      photoresist processing adds a large broad luminescence peak to the Raman spectrum
      of the h-BN flake. This signal persists through typical furnace annealing recipes
      (Ar/H(2)). A recipe that successfully removes organic contaminants and results in
      clean h-BN flakes involves treatment in Ar/O(2) at 500  degrees C.

PMID- 22866699
TI  - Flocculation and haze removal from crude beer using in-house produced laccase
      from Trametes versicolor cultured on brewer's spent grain.
AB  - The potential of brewer's spent grain (BSG), a common waste from the brewing
      industry, as a support-substrate for laccase production by the well-known laccase
      producer Trametes versicolor ATCC 20869 under solid-state fermentation conditions
      was assessed. An attempt was made to improve the laccase production by T.
      versicolor through supplementing the cultures with inducers, such as 2,2-azino
      bis(3-ethylbenzthiazoline-6-sulfonic acid), copper sulfate, ethanol, gallic acid,
      veratryl alcohol, and phenol. A higher laccase activity of 13506.2 +/- 138.2
      IU/gds (gram dry substrate) was obtained with a phenol concentration of 10 mg/kg
      substrate in a tray bioreactor after 12 days of incubation time. The flocculation
      properties of the laccase treated crude beer samples have been studied by using
      various parameters, such as viscosity, turbidity, zeta potential, total
      polyphenols, and total protein content. The present results indicated that
      laccase (25 IU/L) showed promising results as a good flocculating agent. The
      laccase treatment showed better flocculation capacity compared to the industrial
      flocculation process using stabifix as a flocculant. The laccase treatments (25
      IU/L) at 4 +/- 1  degrees C and room temperature have shown almost similar
      flocculation properties without much variability. The study demonstrated the
      potential of in-house produced laccase using brewer's spent grain for the
      clarification and flocculation of crude beer as a sustainable alternative to
      traditional flocculants, such as stabifix and bentonite.

PMID- 22866697
TI  - Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower
      oil in the Mongolian gerbil ( Meriones unguiculatus ).
AB  - Evidence suggests that monounsaturated and polyunsaturated fats facilitate
      greater absorption of carotenoids than saturated fats. However, the comparison of
      consuming a polyunsaturated fat source versus a saturated fat source on tomato
      carotenoid bioaccumulation has not been examined. The goal of this study was to
      determine the influence of coconut oil and safflower oil on tomato carotenoid
      tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat
      diet. Coconut oil feeding increased carotenoid concentrations among many
      compartments including total carotenoids in the serum (p = 0.0003), adrenal
      glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all
      trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal
      vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater
      splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils.
      Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased
      hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut
      oil enhanced tissue uptake of tomato carotenoids to a greater degree than
      safflower oil. These results may have been due to the large proportion of medium
      chain fatty acids in coconut oil, which might have caused a shift in cholesterol
      flux to favor extrahepatic carotenoid tissue deposition. 

PMID- 22866750
TI  - Layer-by-layer self-assembled multilayer films composed of graphene/polyaniline
      bilayers: high-energy electrode materials for supercapacitors.
AB  - Multilayer assemblies of uniform ultrathin film electrodes with good electrical
      conductivity and very large surface areas were prepared for use as
      electrochemical capacitors. A layer-by-layer self-assembly approach was employed
      in an effort to improve the processability of highly conducting polyaniline
      (PANi) and chemically modified graphene. The electrochemical properties of the
      multilayer film (MF-) electrodes, including the sheet resistance, volumetric
      capacitance, and charge/discharge ratio, were determined by the morphological
      modification and the method used to reduce the graphene oxide (GO) to reduced
      graphene oxide (RGO) in the multilayer films. The PANi and GO concentrations
      could be modulated to control the morphology of the GO monolayer film in the
      multilayer assemblies. Optical ellipsometry was used to determine the thickness
      of the GO film in a single layer (1.32 nm), which agreed well with the literature
      value (~1.3 nm). Hydroiodic acid (HI), hydrazine, or pyrolysis were tested for
      the reduction of GO to RGO. HI was found to be the most efficient technique for
      reducing the GO to RGO in the multilayer assemblies while minimizing damage to
      the virgin state of the acid-doped PANi. Ultimately, the MF-electrode, which
      could be optimized by fine-tuning the nanostructure and selecting a suitable
      reduction method, exhibited an excellent volumetric capacitance, good cycling
      stability, and a rapid charge/discharge rate, which are required for
      supercapacitors. A MF-electrode composed of 15 PANi/RGO bilayers yielded a
      volumetric capacitance of 584 F/cm(3) at a current density of 3.0 A/cm(3).
      Although this value decreased exponentially as the current density increased,
      approaching a value of 170 F/cm(3) at 100 A/cm(3), this volumetric capacitance is
      one of the best yet reported for the other carbon-based materials. The intriguing
      features of the MF-electrodes composed of PANi/RGO multilayer films offer a new
      microdimensional design for high energy storage devices for use in small portable
      electronic devices.

PMID- 22866751
TI  - Heterozygosity for E292V in ABCA3, lung function and COPD in 64,000 individuals.
AB  - BACKGROUND: Mutations in ATP-binding-cassette-member A3 (ABCA3) are related to
      severe chronic lung disease in neonates and children, but frequency of chronic
      lung disease due to ABCA3 mutations in the general population is unknown. We
      tested the hypothesis that individuals heterozygous for ABCA3 mutations have
      reduced lung function and increased risk of COPD in the general population.
      METHODS: We screened 760 individuals with extreme pulmonary phenotypes and
      identified three novel (H86Y, A320T, A1086D) and four previously described
      mutations (E292V, P766S, S1262G, R1474W) in the ABCA3 gene. We genotyped the
      entire Copenhagen City Heart study (n = 10,604) to assess the clinical importance
      of these mutations. To validate our findings we genotyped an additional 54,395
      individuals from the Copenhagen General Population Study. RESULTS: In the
      Copenhagen City Heart Study individuals heterozygous for E292V had 5% reduced
      FEV1 % predicted compared with noncarriers (t-test: p = 0.008), and an increased
      odds ratio for COPD of 1.9 (95% CI: 1.1-3.1). In contrast, the A1086D mutation
      was associated with increased FEVFEV1 % predicted (p = 0.03). None of the other
      ABCA3 mutations associated with lung function or COPD risk in the Copenhagen City
      Heart Study. In the larger Copenhagen General Population Study, and in the two
      studies combined, E292V heterozygotes did not have reduced lung function or
      increased risk of COPD (p = 0.11-0.98), while this was the case for the positive
      controls, surfactant protein-B 121ins2 heterozygotes and alpha1-antitrypsin ZZ
      homozygotes. CONCLUSION: Our results indicate that partially reduced ABCA3
      activity due to E292V is not a major risk factor for reduced lung function and
      COPD in the general population. This is an important finding as 1.3% in the
      Danish population has partially reduced ABCA3 function due to E292V.

PMID- 22866752
TI  - A cross sectional assessment of health related quality of life among patients
      with Hepatitis-B in Pakistan.
AB  - OBJECTIVE: The study aims to assess Health Related Quality of Life (HRQoL) among
      Hepatitis B (HB) patients and to identify significant predictors of the HRQoL in
      HB patients of Quetta, Pakistan. METHODS: A cross sectional study by adopting
      European Quality of Life scale (EQ-5D) for the assessment of HRQoL was conducted.
      All registered HB patients attending two public hospitals in Quetta, Pakistan
      were approached for study. Descriptive statistics were used to describe
      demographic and disease related characteristics of the patients. HRQoL was scored
      using values adapted from the United Kingdom general population survey. EQ-5D
      scale scores were compared with Mann-Whitney and Kruskal-Wallis test. Standard
      multiple regression analysis was performed to identify predictors of HRQoL. All
      analyses were performed using SPSS v 16.0. RESULTS: Three hundred and ninety HB
      patients were enrolled in the study. Majority of the participants (n = 126,
      32.3%) were categorized in the age group of 18-27 years (36.07 +/- 9.23). HRQoL
      was measured as poor in the current study patients (0.3498 +/- 0.31785). The
      multivariate analysis revealed a significant model (F(10, 380) = 40.04, P <
      0.001, adjusted r(2) = 0.401). Educational level (beta = 0.399, p = 0.025)
      emerged as a positive predictor of HRQoL. Age, gender, occupation, income and
      locality were not predictive of better quality of life in HB patients.
      CONCLUSIONS: Hepatitis B has an adverse affect on patients' well-being and over
      all HRQoL. The study findings implicate the need of health promotion among HB
      patients. Improving the educational status and imparting disease related
      information for the local population can results in better control and management
      of HB.

PMID- 22866753
TI  - Interest of pregnant women in the use of SMS (short message service) text
      messages for the improvement of perinatal and postnatal care.
AB  - BACKGROUND: Mobile health (mHealth) is emerging as a useful tool to improve
      healthcare access especially in the developing world, where limited access to
      health services is linked to poor antenatal care, and maternal and perinatal
      mortality.The objective of this study is to 1) understand pregnant women's access
      and usage of cell phones and 2) survey the health information needs and interests
      in a population attending public hospitals and health centers of two cities in
      Argentina. This information is not available and it is the basis to develop a
      strategy for improving maternal care via cell phones. METHODS: Questionnaires
      were verbally administered to pregnant women who were attending an antenatal care
      visit in community health centers and public hospitals in Rosario, Santa Fe and
      Mercedes, Corrientes. Participants were 18 years of age or older and had
      previously given birth. The data obtained was qualitative and analyzed using SPSS
      version 18. RESULTS: A total of 147 pregnant women meeting inclusion criteria
      (Rosario: 63; Mercedes: 84) were approached and verbally consented to
      participate. The average age was 29.5 years, most lived in urban areas (89%) with
      a mean travel time of 43.4 minutes required to get to the health center and 57.3
      minutes to get the hospital.Ninety-six percent of women (n = 140) responded that
      they would like to receive text messages and cell phone calls with information
      regarding prenatal care, although the topics and period of time to receive
      information varied greatly. CONCLUSIONS: Considering the vast majority of the
      interviewed women had access to and were interested in receiving text messages
      and calls with educational information regarding pregnancy and infant health,
      pregnant women in Argentina could benefit from such an mHealth program. The low
      access to Internet suggests it is not an option for this population; however,
      this cannot be assumed as representative of the country's situation.To retain
      active participation, other forms of health communication, such as a 2-way text
      message systems or toll-free numbers, could be considered in the future. Cost of
      use and implementing these options should be studied.

PMID- 22866754
TI  - A case of rapidly progressive IgA nephropathy in a patient with exacerbation of
      Crohn's disease.
AB  - BACKGROUND: IgA nephropathy has been reported as a renal involvement in Crohn's
      disease. Crescentic IgA nephropathy, which accounts for fewer than 5% of cases of
      IgA nephropathy, has a poorer prognosis than other forms of crescentic
      glomerulonephritis. We recently experienced a case of rapidly progressive IgA
      nephropathy concurrent with exacerbation of Crohn's disease. CASE PRESENTATION:
      An 18-year-old male diagnosed with Crohn's disease underwent a hemicolectomy 2
      years prior previously. He had maintained a state of Crohn's disease remission
      with 5-aminosalicylic acid treatment. Four months prior to referral to the
      nephrology clinic, he experienced non-bloody diarrhea. He simultaneously
      developed proteinuria and microscopic hematuria with deterioration of renal
      function. Based on renal biopsy findings, the patient was diagnosed with
      crescentic IgA nephropathy. Immunostaining for interleukin-17 in renal tissue and
      previous exacerbated colonic ulcers was positive. Steroid pulse therapy was
      administered, followed by high-dose glucocorticoid and oral cyclophosphamide
      therapy. The patient's renal function recovered and his gastrointestinal symptoms
      were alleviated. CONCLUSIONS: We report a case of crescentic IgA nephropathy
      presenting with exacerbation of Crohn's disease, and present a review of the
      literature focusing on the pathophysiologic relationship between these two
      conditions.

PMID- 22866755
TI  - Surgical treatment modality for facial esthetics in an obstructive sleep apnea
      patient with protrusive upper lip and acute nasolabial angle.
AB  - For patients with severe obstructive sleep apnea syndrome (OSAS),
      maxillomandibular advancement (MMA) offers a good treatment option by physically
      expanding the skeletal framework. However, facial esthetics can be aggravated by
      MMA in patients with OSAS who have a normally positioned maxilla, a protrusive
      upper lip, and an acute nasolabial angle. Therefore, surgical treatment planning
      should be customized according to diverse skeletodental and soft-tissue patterns
      to produce a favorable change in facial esthetics and sleep function in patients
      with OSAS. In this case report, good treatment results were achieved in a young
      female patient with OSAS and skeletal Class II, a normally positioned maxilla, a
      protrusive upper lip, and acute nasolabial angle by impaction of the maxilla,
      autorotation/advancement of the mandible, and advancement of the chin. A
      customized flowchart for surgical treatment planning in OSAS that considers
      facial esthetics was suggested.

PMID- 22866756
TI  - Dental arch parameters of the displacement and nondisplacement sides in subjects
      with unilateral palatal canine ectopia.
AB  - OBJECTIVE: To compare arch perimeter and teeth size, number, and shape between
      the two sides of the dental arch-the canine displacement side (DS) and the
      nondisplacement side (NDS)-in subjects with unilateral palatally displaced canine
      (PDC). MATERIALS AND METHODS: Orthopantomograms (OPTs) of 240 subjects with
      unilateral PDC and 240 OPT matching controls were used. Additionally, study casts
      of 100 study subjects and 100 controls were used. The age of subjects ranged
      between 14 and 25 years. Dental casts were digitized and several parameters were
      recorded. RESULTS: The transverse width from midpalatal line to the buccal
      segment and the palatal area on the DS was larger than that in the NDS (P < .05
      to .001), with no difference in tooth size between both sides. Maxillary second
      premolars, canines, and lateral incisors in the PDC group were smaller than those
      in control group. Peg-shaped lateral incisors were significantly more frequent in
      the study group (P < .001). CONCLUSIONS: The transverse width of the DS was
      larger than that of the NDS. Both sides were generally smaller than those of the
      control group. Tooth size in the DS was comparable to that in the NDS but smaller
      than those of the control group. A missing or peg-shaped lateral incisor was the
      most common reported anomaly.

PMID- 22866757
TI  - In memorium.

PMID- 22866758
TI  - Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and
      IL-18 enhanced chickens immune responses.
AB  - BACKGROUND: DNA vaccines offer several advantages over conventional vaccines in
      the development of effective vaccines against avian influenza virus (AIV).
      However, one of the limitations of the DNA vaccine in poultry is that it induces
      poor immune responses. In this study, chicken interleukin (IL) -15 and IL-18 were
      used as genetic adjuvants to improve the immune responses induced from the H5 DNA
      vaccination in chickens. The immunogenicity of the recombinant plasmid DNA was
      analyzed based on the antibody production, T cell responses and cytokine
      production, following inoculation in 1-day-old (Trial 1) and 14-day-old (Trial 2)
      specific-pathogen-free chickens. Hence, the purpose of the present study was to
      explore the role of chicken IL-15 and IL-18 as adjuvants following the
      vaccination of chickens with the H5 DNA vaccine. RESULTS: The overall HI antibody
      titer in chickens immunized with pDis/H5 + pDis/IL-15 was higher compared to
      chickens immunized with pDis/H5 (p < 0.05). The findings revealed that the
      inoculation of the 14-day-old chickens exhibited a shorter time to achieve the
      highest HI titer in comparison to the inoculation of the 1-day-old chickens. The
      cellular immunity was assessed by the flow cytometry analysis to enumerate CD4+
      and CD8 + T cells in the peripheral blood. The chickens inoculated with pDis/H5 +
      pDis/IL-15 demonstrated the highest increase in CD4+ T cells population relative
      to the control chickens. However, this study revealed that pDis/H5 + pDis/IL-15
      was not significant (P > 0.05) in inducing CD8+ T cells. Meanwhile, with the
      exception of Trial 1, the flow cytometry results for Trial 2 demonstrated that
      the pDis/H5 + pDis/IL-18 inoculated group was able to trigger a higher increase
      in CD4+ T cells than the pDis/H5 group (P < 0.05). On the other hand, the pDis/H5
      + pDis/IL-18 group was not significant (P > 0.05) in modulating CD8+ T cells
      population in both trials. The pDis/H5 + pDis/IL-15 inoculated group showed the
      highest IL-15 gene expression in both trials compared to other inoculated groups
      (P < 0.05). Similar results were obtained for the IL-18 expression where the
      pDis/H5 + pDis/IL-18 groups in both trials (Table 8) were significantly higher
      compared to the control group (P < 0.05). However, the expressions of other
      cytokines remained low or undetected by GeXP assay. CONCLUSIONS: This study shows
      the diverse immunogenicity of pDis/H5 co-administered with chicken IL-15 and IL
      18,with pDis/H5 + pDis/IL-15 being a better vaccine candidate compared to other
      groups.

PMID- 22866759
TI  - A model-based statistic for detecting molecular markers associated with complex
      survival patterns in early-stage cancer.
AB  - BACKGROUND: In early-stage of cancer, primary treatment can be considered as
      effective at eliminating the tumor for a non-negligible proportion of patients
      whereas for the others it leads to a lower tumor burden and thereby potentially
      prolonged survival. In this mixed population of patients, it is of great interest
      to detect complex differences in survival distributions associated with molecular
      markers that potentially activate latent downstream pathways implicated in tumor
      progression. METHOD: We propose a novel model-based score test designed for
      identifying molecular markers with complex effects on survival in early-stage
      cancer. From a biological point of view, the proposed score test allows to detect
      complex changes in the survival distributions linked to either the tumor burden
      or its dynamic growth. RESULTS: Simulation results show that the proposed
      statistic is powerful at identifying departure from the null hypothesis of no
      survival difference. The practical use of the proposed statistic is exemplified
      by analyzing the prognostic impact of Kras mutation in early-stage of lung
      adenocarcinomas. This analysis leads to the conclusion that Kras mutation has a
      significant negative prognostic impact on survival. Moreover, it emphasizes that
      the complex role of Kras mutation on survival would have been overlooked by
      considering results from the classical logrank test. CONCLUSION: With the growing
      number of biological markers to be tested in early-stage cancer, the proposed
      score test statistic is a powerful tool for detecting molecular markers
      associated with complex survival patterns.

PMID- 22866760
TI  - Perceiving and reenacting spatiotemporal characteristics of walking sounds.
AB  - Many studies have examined the processes involved in recognizing types of human
      action through sound, but little is known about whether the physical
      characteristics of an action (such as kinetic and kinematic parameters) can be
      perceived and imitated from sound. Twelve young healthy adults listened to
      recordings of footsteps on a gravel path taken from walks of different stride
      lengths (SL) and cadences. In 1 protocol, participants performed a real-time
      reenactment of the walking action depicted in a sound sample. Second,
      participants listened to 2 different sound samples and discriminated differences
      in SL. In a 2nd experiment, these procedures were repeated using synthesized
      sounds derived from the kinetic interactions between the foot and walking
      surface. A 3rd experiment examined the influence of altered cadence on
      participants' ability to discriminate changes in SL. Participants significantly
      adapted their own SL and cadence according to those depicted in both real and
      synthesized sounds (p < .01). However, although participants accurately
      discriminated between large changes in SL, these perceptions were heavily
      influenced by temporal factors, that is, when cadence changed between samples.
      These findings show that spatial attributes of action sounds can be both mimicked
      and discriminated, even when only basic kinetic interactions present within the
      action are specified.

PMID- 22866762
TI  - When humanoid robots become human-like interaction partners: corepresentation of
      robotic actions.
AB  - In human-human interactions, corepresenting a partner's actions is crucial to
      successfully adjust and coordinate actions with others. Current research suggests
      that action corepresentation is restricted to interactions between human agents
      facilitating social interaction with conspecifics. In this study, we investigated
      whether action corepresentation, as measured by the social Simon effect (SSE), is
      present when we share a task with a real humanoid robot. Further, we tested
      whether the believed humanness of the robot's functional principle modulates the
      extent to which robotic actions are corepresented. We described the robot to
      participants either as functioning in a biologically inspired human-like way or
      in a purely deterministic machine-like manner. The SSE was present in the human
      like but not in the machine-like robot condition. These findings suggest that
      humans corepresent the actions of nonbiological robotic agents when they start to
      attribute human-like cognitive processes to the robot. Our findings provide novel
      evidence for top-down modulation effects on action corepresentation in human
      robot interaction situations.

PMID- 22866761
TI  - Flicker adaptation of low-level cortical visual neurons contributes to temporal
      dilation.
AB  - Several seconds of adaptation to a flickered stimulus causes a subsequent brief
      static stimulus to appear longer in duration. Nonsensory factors, such as
      increased arousal and attention, have been thought to mediate this flicker-based
      temporal-dilation aftereffect. In this study, we provide evidence that adaptation
      of low-level cortical visual neurons contributes to this aftereffect. The
      aftereffect was significantly reduced by a 45 degrees  change in Gabor
      orientation between adaptation and test. Because orientation-tuning bandwidths
      are smaller in lower-level cortical visual areas and are approximately 45 degrees
      in human V1, the result suggests that flicker adaptation of orientation-tuned V1
      neurons contributes to the temporal-dilation aftereffect. The aftereffect was
      abolished when the adaptor and test stimuli were presented to different eyes.
      Because eye preferences are strong in V1 but diminish in higher-level visual
      areas, the eye specificity of the aftereffect corroborates the involvement of low
      level cortical visual neurons. Our results suggest that flicker adaptation of low
      level cortical visual neurons contributes to expanding visual duration.
      Furthermore, this temporal-dilation aftereffect dissociates from the previously
      reported temporal-compression aftereffect on the basis of the differences in
      their orientation and flicker-frequency selectivity, suggesting that the visual
      system possesses at least two distinct and potentially complementary mechanisms
      for adaptively coding perceived duration.

PMID- 22866763
TI  - Investigating perfect timesharing: the relationship between IM-compatible tasks
      and dual-task performance.
AB  - Why are dual-task costs reduced with ideomotor (IM) compatible tasks (Greenwald &
      Shulman, 1973; Lien, Proctor & Allen, 2002)? In the present experiments, we first
      examine three different measures of single-task performance (pure single-task
      blocks, mixed blocks, and long stimulus onset asynchrony [SOA] trials in dual
      task blocks) and two measures of dual-task performance (simultaneous stimulus
      presentation blocks and simultaneous stimulus presentation trials in blocks with
      mixed SOAs), and show that these different measures produce different estimates
      of the cost. Next we examine whether the near elimination of costs can be
      explained by assuming that one or both of the tasks bypasses capacity-limited
      central operations. The results indicate that both tasks must be IM-compatible to
      nearly eliminate the dual-task costs, suggesting that the relationship between
      the tasks plays a critical role in overlapping performance.

PMID- 22866764
TI  - Parafoveal-foveal overlap can facilitate ongoing word identification during
      reading: evidence from eye movements.
AB  - Readers continuously receive parafoveal information about the upcoming word in
      addition to the foveal information about the currently fixated word. Previous
      research (Inhoff, Radach, Starr, & Greenberg, 2000) showed that the presence of a
      parafoveal word that was similar to the foveal word facilitated processing of the
      foveal word. We used the gaze-contingent boundary paradigm (Rayner, 1975) to
      manipulate the parafoveal information that subjects received before or while
      fixating a target word (e.g., news) within a sentence. Specifically, a reader's
      parafovea could contain a repetition of the target (news), a correct preview of
      the posttarget word (once), an unrelated word (warm), random letters (cxmr), a
      nonword neighbor of the target (niws), a semantically related word (tale), or a
      nonword neighbor of that word (tule). Target fixation times were significantly
      lower in the parafoveal repetition condition than in all other conditions,
      suggesting that foveal processing can be facilitated by parafoveal repetition. We
      present a simple model framework that can account for these effects.

PMID- 22866765
TI  - Estimation of return-to-sports-time for athletes with stress fracture - an
      approach combining risk level of fracture site with severity based on imaging.
AB  - BACKGROUND: The aim was to compare the return-to-sports-time (RTST) following
      stress fractures on the basis of site and severity of injury. This retrospective
      study was set up at a single institution. Diagnosis was confirmed by an
      interdisciplinary adjudication panel and images were rated in a blinded-read
      setting. METHODS: 52 athletes (female, n = 30; male, n = 22; mean age, 22.8
      years) with stress fracture (SFX) who had undergone at least one examination,
      either MRI or bone scintigraphy, were included. Magnetic resonance images (MRI)
      and/or bone scintigraphy (BS) of SFX were classified as either low- or high-grade
      SFX, according to existing grading systems. For MRI, high-grade SFX was defined
      as visibility of a fracture line or bone marrow edema in T1-, T2-weighted and
      short tau inversion recovery (STIR) sequences, with low-grade SFX showing no
      fracture line and bone marrow edema only in STIR and/or T2-weighted sequences. In
      BS images, a mild and poorly defined focal tracer uptake represented a low-grade
      lesion, whereas an intense and sharply marginated uptake marked a high-grade SFX.
      In addition, all injuries were categorized by location as high- or low-risk
      stress fractures. RTST was obtained from the clinical records. All patients were
      treated according to a non-weight-bearing treatment plan and comprehensive follow
      up data was complete until full recovery. Two-sided Wilcoxon's rank sum test was
      used for group comparisons. RESULTS: High-risk SFX had a mean RTST of 132 days
      (d) [IQR 64d - 132d] compared to 119d [IQR 50d - 110d] for low-risk sites (p =
      0.19). RTST was significantly longer (p = 0.01) in high-grade lesions [mean,
      143d; IQR 66d - 134d] than in low-grade [mean, 95d; IQR 42d - 94d]. Analysis of
      high-risk SFX showed no difference in RTST (p = 0.45) between high- and low-grade
      [mean, 131d; IQR 72d - 123d vs. mean, 135d; IQR 63d - 132d]. In contrast, the
      difference was significant for low-risk SFX (p = 0.005) [low-grade; mean, 61d;
      IQR 35d - 78d vs. high-grade; mean, 153d; IQR 64d - 164d]. CONCLUSION: For SFX at
      low-risk sites, the significant difference in RTST between low- and high-grade
      lesions allows more accurate estimation of RTST by this approach. Both location
      of the injury and severity determined by imaging should therefore be considered
      for prediction of RTST.

PMID- 22866766
TI  - Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal.
AB  - CONTEXT: Ciclopirox olamine (CPO) is indicated in the treatment of vaginal fungal
      infections. The frequent and large dosing of available vaginal CPO creams gives
      rise to poor compliance amongst females. In such a situation a delivery system
      capable of providing sustained release of CPO is warranted and can be realized
      through incorporation of its liposomal formulation into a mucoadhesive gel base.
      The liposomal formulation would offer sustained release whereas mucoadhesive gel
      would prolong the contact with vaginal wall; thus avoiding frequent and large
      dosing. OBJECTIVE: The present study aimed at investigating mucoadhesive
      liposomal CPO gel for vaginal use. METHOD: The study embarked on evaluating
      liposomal CPO and its Carbopol 974(r)P gel for stability at vaginal pH, release
      profile, rheological characteristics, mucoadhesive behavior and finally
      antifungal activity. RESULTS: The results revealed that CPO liposomes were stable
      at vaginal pH; its Carbopol gel released 58.75 +/- 6.4% of CPO at the end of 24 h
      which suggested sustained release. Rheology via viscometric, oscillatory stress
      sweep and oscillatory frequency sweep testing of the gel, studied at different
      temperatures and under different dilutions with vaginal fluid simulant testified
      pseudoplastic behavior of the gel. It also pointed towards the predominance of
      elastic behavior of the gel at all the dilutions. The gel exhibited good
      mucoadhesivity to sheep vaginal tissue. Furthermore, CPO entrapped in liposome
      too displayed antifungal activity. CONCLUSION: The study undertaken recommended
      Carbopol 974(r)P gel loaded with CPO liposomes as a potential delivery system for
      treatment of fungal vaginal infections.

PMID- 22866767
TI  - Comparing marginal structural models to standard methods for estimating treatment
      effects of antihypertensive combination therapy.
AB  - BACKGROUND: Due to time-dependent confounding by blood pressure and differential
      loss to follow-up, it is difficult to estimate the effectiveness of aggressive
      versus conventional antihypertensive combination therapies in non-randomized
      comparisons. METHODS: We utilized data from 22,576 hypertensive coronary artery
      disease patients, prospectively enrolled in the INternational VErapamil
      Trandolapril STudy (INVEST). Our post-hoc analyses did not consider the
      randomized treatment strategies, but instead defined exposure time-dependently as
      aggressive treatment (>=3 concomitantly used antihypertensive medications) versus
      conventional treatment (<=2 concomitantly used antihypertensive medications).
      Study outcome was defined as time to first serious cardiovascular event (non
      fatal myocardial infarction, non-fatal stroke, or all-cause death). We compared
      hazard ratio (HR) estimates for aggressive vs. conventional treatment from a
      Marginal Structural Cox Model (MSCM) to estimates from a standard Cox model. Both
      models included exposure to antihypertensive treatment at each follow-up visit,
      demographics, and baseline cardiovascular risk factors, including blood pressure.
      The MSCM further adjusted for systolic blood pressure at each follow-up visit,
      through inverse probability of treatment weights. RESULTS: 2,269 (10.1%) patients
      experienced a cardiovascular event over a total follow-up of 60,939 person-years.
      The HR for aggressive treatment estimated by the standard Cox model was 0.96 (95%
      confidence interval 0.87-1.07). The equivalent MSCM, which was able to account
      for changes in systolic blood pressure during follow-up, estimated a HR of 0.81
      (95% CI 0.71-0.92). CONCLUSIONS: Using a MSCM, aggressive treatment was
      associated with a lower risk for serious cardiovascular outcomes compared to
      conventional treatment. In contrast, a standard Cox model estimated similar risks
      for aggressive and conventional treatments. TRIAL REGISTRATION:
      Clinicaltrials.gov Identifier: NCT00133692.

PMID- 22866769
TI  - Vocal sharing and individual acoustic distinctiveness within a group of captive
      orcas (Orcinus orca).
AB  - Among vocal learners, some animal species are known to develop individually
      distinctive vocalizations, and others clearly learn to produce group signatures.
      The optimal vocal sharing hypothesis suggests that vocal divergence and
      convergence are not compulsorily exclusive and both can be found at different
      levels in a given species. Being individually recognizable is socially important
      even in species sharing vocal badges. Acoustic divergence is not systematically
      controlled as it can simply be due to interindividual morphological differences.
      We tested that hypothesis in a species known to learn their family vocal dialect
      socially: the orca (Orcinus orca). We identified 13 different call types,
      including some shared by all group members, some shared only by 2 or 3
      individuals, and others particular to 1 individual. Sharing was higher between
      males than between females. Three of our 4 orcas each produced a unique call
      type, which was preferably emitted. The call types shared by all orcas still
      presented individual acoustic distinctiveness that could, to some degree, be
      explained by morphological differences. We found evidence for strong similarities
      between some of the call types of our captive orcas and the call types of their
      ancestors, which are Canadian and Icelandic free-ranging orcas. Our findings
      suggest that captive orcas use a complex vocal repertoire enabling each
      individual to produce sounds that are similar to some of their partners', which
      might be used as social badges to advertise their preferential bonds, as well as
      individual-specific calls. Our findings open new lines of research concerning the
      functional value of a balanced "diverging-converging" vocal system.

PMID- 22866768
TI  - Effect of lycopene on cell viability and cell cycle progression in human cancer
      cell lines.
AB  - BACKGROUND: Lycopene, a major carotenoid component of tomato, has a potential
      anticancer activity in many types of cancer. Epidemiological and clinical trials
      rarely provide evidence for mechanisms of the compound's action, and studies on
      its effect on cancer of different cell origins are now being done. The aim of the
      present study was to determine the effect of lycopene on cell cycle and cell
      viability in eight human cancer cell lines. METHODS: Human cell lines were
      treated with lycopene (1-5 MUM) for 48 and 96 h. Cell viability was monitored
      using the method of MTT. The cell cycle was analyzed by flow cytometry, and
      apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated
      dUTP nick labeling (TUNEL) and by DAPI. RESULTS: Our data showed a significant
      decrease in the number of viable cells in three cancer cells lines (HT-29, T84
      and MCF-7) after 48 h treatment with lycopene, and changes in the fraction of
      cells retained in different cell cycle phases. Lycopene promoted also cell cycle
      arrest followed by decreased cell viability in majority of cell lines after 96 h,
      as compared to controls. Furthermore, an increase in apoptosis was observed in
      four cell lines (T-84, HT-29, MCF-7 and DU145) when cells were treated with
      lycopene. CONCLUSIONS: Our findings show the capacity of lycopene to inhibit cell
      proliferation, arrest cell cycle in different phases and increase apoptosis,
      mainly in breast, colon and prostate lines after 96 h. These observations suggest
      that lycopene may alter cell cycle regulatory proteins depending on the type of
      cancer and the dose of lycopene administration. Taken together, these data
      indicated that the antiproliferative effect of lycopene was cellular type, time
      and dose-dependent.

PMID- 22866770
TI  - Rotational displacement skills in rhesus macaques (Macaca mulatta).
AB  - Rotational displacement tasks, in which participants must track an object at a
      hiding location within an array while the array rotates, exhibit a puzzling
      developmental pattern in humans. Human children take an unusually long time to
      master this task and tend to solve rotational problems through the use of
      nongeometric features or landmarks as opposed to other kinds of spatial cues. We
      investigated whether these developmental characteristics are unique to humans by
      testing rotational displacement skills in a monkey species, the rhesus macaque
      (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in
      two differently colored boxes within an array. The array was then rotated 180
      degrees  and the boxes reopened to reveal the food in an expected or unexpected
      location. Our first two experiments explored the developmental time-course of
      performance on this rotational displacement task. We found that adult macaques
      looked longer at the unexpected event, but such performance was not mirrored in
      younger-aged macaques. In a third study, we systematically varied featural
      information and visible access to the array to investigate which strategies adult
      macaques used in solving rotational displacements. Our results show that adult
      macaques need both sets of information to solve the task. Taken together, these
      results suggest both similarities and differences in mechanisms by which human
      and nonhuman primates develop this spatial skill.

PMID- 22866771
TI  - Does a nonprimate mammal, the northern tree shrew (Tupaia belangeri), exhibit paw
      preference in two forms of a grasping task?
AB  - Tree shrews represent a relevant model to study the evolution of primate manual
      laterality as they are phylogenetically close to primates, they are able to grasp
      despite having a nonopposable thumb, and they possess a well-developed visual
      system. In this study, we examined the paw laterality and grasping success rate
      of 30 Tupaia belangeri (15 males, 15 females) in 2 forced-food grasping tasks
      (i.e., in a forced-food grasping experiment, the animal has to use paws instead
      of mouth for food retrieval). We also attempted to determine whether paw usage
      would be affected by the availability of visual cues using both a visual task
      (transparent tube) and a nonvisual task (identical but opaque tube). In both
      tasks, tree shrews showed paw preferences at an individual but not at a
      population level. Paw laterality (direction and strength) did not differ between
      tasks. Moreover, in the specific task that we used, grasping success rate was not
      affected by an absence of visual cues, indicating that tree shrews did not rely
      on visual guidance to direct their grasps in this forced-food grasping
      experiment. Our findings suggest that, in contrast to primates, paw usage in tree
      shrews may result from a modification of a fixed motor pattern in which the
      preferred direction may be learned. This basic motor organization might be a
      first step in the evolution of manual laterality, which eventually became
      controlled by vision in the primate lineage.

PMID- 22866772
TI  - Adaptive forgetting in Iberian green frog tadpoles (Pelophylax perezi): learned
      irrelevance and latent inhibition may avoid predator misidentification.
AB  - Predator recognition often requires learning by prey individuals. Iberian green
      frog tadpoles (Pelophylax perezi) have the ability to learn to recognize new
      potential predators when their chemical cues are found paired with conspecific
      alarm cues. However, a random pairing of alarm cues and chemical stimuli of a
      nonpredator might later induce costly antipredator responses to nondangerous
      species. Here, we studied the potential existence in this frog species of two
      phenomena (learned irrelevance and latent inhibition) that could help tadpoles to
      avoid these nonadaptive responses to chemical cues of nonpredator species. Our
      results showed that, when tadpoles experienced a random pattern of presence of
      alarm cues alone or predator cues alone over the 4 days before or after the
      simultaneous detection of these two cues paired, no learned association was
      formed. These results showed the existence of an effect of learned irrelevance on
      learning in Iberian green frog tadpoles. Also, tadpoles clearly inhibited the
      formation of a learning association between predator and alarm cues after a 4-day
      period during which they had been exposed to the predator cues alone. This result
      showed the existence of an effect of latent inhibition on learning about cues
      related to increased predation risk. Thus, both learned irrelevance and latent
      inhibition, rather than being considered to be failed predator recognition, can
      rather be seen as adaptive ways for dealing with conflicting information and as
      strategies to avoid learning irrelevant information and costly antipredatory
      responses to nonpredatory stimuli.

PMID- 22866773
TI  - The influence of local enhancement on choice performances in African Grey parrots
      (Psittacus erithacus) and jackdaws (Corvus monedula).
AB  - Being attentive to the behavior of others may be advantageous to gain important
      information, for example, on the location of food. Often, this is achieved
      through simple local enhancement. However, this is not always beneficial, as it
      may override cognitive abilities, with negative consequences. Grey parrots
      (Psittacus erithacus) and ravens have already succeeded in exclusion tasks, but
      carrion crows do so only when controlling for local enhancement, and jackdaws
      (Corvus monedula) fail entirely. Presently, we tested whether jackdaws would
      still be influenced by local enhancement in a simple choice-task. We compared
      their performance with those of Grey parrots. Since these birds did not respond
      to enhancement in the exclusion task, we expected them also to be less
      susceptible to enhancement here. In our tasks, two pieces of food were visibly
      hidden under two cups. Then one cup was lifted, the reward was shown to the bird
      and was either laid back underneath the cup or was removed. Alternatively, both
      manipulations were combined with the first reward being shown to the bird and the
      second one being removed or vice versa. Surprisingly, both species had a
      preference for the last handled cup, irrespective of whether it contained food or
      not. However, if the birds had to wait for 10 seconds after the presentation, the
      jackdaws performed better than the Grey parrots. Additionally, the delay improved
      the performance of both species in conditions in which the reward was removed
      last and deteriorated their performance in conditions in which the item was shown
      last.

PMID- 22866774
TI  - Extinction of food-reinforced instrumental behavior in Japanese quail (Coturnix
      japonica).
AB  - Japanese quail (Coturnix japonica) were reinforced with food for traversing a
      runway for either 18 or 36 trials, administered at a rate of 1 trial per day.
      Then, all animals received 18 extinction trials. The latency to run from the
      start box to the goal box was the dependent variable. Extinction was
      significantly slower in animals that had received 50% partial reinforcement
      during acquisition, whether relative to a group matched in terms of acquisition
      trials (36 trials, twice the number of reinforced trials) or relative to a group
      matched in terms of reinforcements (18 trials). The latter group was also matched
      in terms of the temporal distribution of acquisition trials with the partial
      reinforcement group, being trained only on days when the partial group was
      scheduled to receive a reinforced trial. Thus, there was evidence of a spaced
      trial partial reinforcement extinction effect. A comparison of groups receiving
      large versus small reward magnitudes yielded no evidence of the spaced-trial
      magnitude of reinforcement extinction effect, even though the large-reward group
      consumed approximately 3 times more food than the small-reward group. Moreover, a
      comparison of groups that received 36 versus 18 acquisition trials produced no
      evidence of the spaced-trial overtraining extinction effect, even though
      acquisition latencies were significantly lower for the group that received 36
      acquisition trials. These results are discussed in relation to comparative
      research on learning phenomena involving incentive downshift manipulations.

PMID- 22866775
TI  - Concordance study: methods of quantifying corn and soybean genomic DNA intended
      for real-time polymerase chain reaction applications.
AB  - Quantitative real-time polymerase chain reaction (qPCR) is a technology commonly
      used for the detection and quantification of genetically engineered (GE) traits
      in grains and oilseeds. The method involves measuring copy numbers of taxon
      specific, endogenous control genes exposed to the same manipulations as trait
      specific target genes. Accurate DNA quantification is essential for successful
      and predictable results with qPCR. A systematic study of seven different DNA
      quantification methods, incorporating different chemistries and different
      instrumentation, were evaluated on corn and soy DNA that was extracted using two
      distinct extraction methods. A time course study showed that corn and soy DNA was
      stable under typical laboratory storage conditions. CornCTAB and cornQiagen DNA
      extracts produced statistically similar quantification values when measured by
      picogreen PG(TD700), PG(Lum20/20), Hoescht(TD700), and Hoescht(Lum20/20) methods,
      suggesting that these methods can be used interchangeably to quantify DNA in corn
      samples prior to initiation of qPCR. Soy(Qiagen) provided greater stochastic
      measurement variability when quantification methods were compared, whereas
      soyCTAB had statistically significant differences when a PG method was compared
      to a Hoescht method of DNA quantification. Finally, agarose gel electrophoresis
      data revealed more pronounced degradation for Qiagen-extracted DNA compared with
      CTAB extracts in both corn and soy. Consequently, Ct values generated by qPCR
      suggested that absolute copy numbers of PCR amplifiable targets were not
      concordant between Qiagen and CTAB DNA extracts. Understanding measurement
      uncertainty from component steps used in qPCR can contribute toward harmonizing
      methods for the detection of GE traits in grains and oilseeds.

PMID- 22866776
TI  - Estimation of Young's modulus of graphene by Raman spectroscopy.
AB  - The Young's modulus of graphene is estimated by measuring the strain applied by a
      pressure difference across graphene membranes using Raman spectroscopy. The
      strain induced on pressurized graphene balloons can be estimated directly from
      the peak shift of the Raman G band. By comparing the measured strain with
      numerical simulation, we obtained the Young's modulus of graphene. The estimated
      Young's modulus values of single- and bilayer graphene are 2.4 +/- 0.4 and 2.0 +/
      0.5 TPa, respectively.

PMID- 22866811
TI  - Morphology of electrophoretically deposited films on electrode strips.
AB  - Studies of the kinetics of electrophoretic deposition (EPD) processes have
      generally focused on electrode geometries that yield analytical solutions, such
      as infinite parallel planes and concentric cylinders. In this article, we
      construct a finite element model for EPD of material onto a planar strip
      electrode, which shows excellent qualitative agreement to experimental results in
      a similar system. Notably, we demonstrate that the presence of the edges of the
      electrode lead to a singularity in the electric field that significantly affects
      the morphology of the deposit at short times or for thin deposits.

PMID- 22866812
TI  - Prenatal transfer of polybrominated diphenyl ethers (PBDEs) results in
      developmental neurotoxicity in zebrafish larvae.
AB  - Parental exposure to polybrominated diphenyl ethers (PBDEs) in animals has been
      found to be transferred to the offspring. The environmental health risk and
      toxicity to the offspring are still unclear. The objective of the present study
      was to identify environmentally relevant concentrations of PBDEs for parental
      exposure that would cause developmental neurotoxicity in the offspring. Adult
      zebrafish were exposed to environmentally relevant concentrations of DE-71 (0.16,
      0.8, 4.0 MUg/L) via water. The results showed that PBDE exposure did not affect
      larvae hatching, malformation, or survival. The residue of PBDEs was detected in
      F1 eggs upon parental exposure. Acetylcholinesterase (AChE) activity was
      significantly inhibited in F1 larvae. Genes of central nervous system development
      (e.g., myelin basic protein, synapsin IIa, alpha1-tubulin) were significantly
      downregulated in larvae. Protein levels of alpha1-tubulin and synapsin IIa were
      also reduced. Decreased locomotion activity was observed in the larvae. This
      study provides the first evidence that parental exposure to environmentally
      relevant concentrations of PBDEs could cause adverse effects on neurodevelopment
      in zebrafish offspring.

PMID- 22866813
TI  - Intrathoracic versus cervical anastomosis after resection of esophageal cancer: a
      matched pair analysis of 72 patients in a single center study.
AB  - BACKGROUND: The aim of this study was to analyze the early postoperative outcome
      of esophageal cancer treated by subtotal esophageal resection, gastric
      interposition and either intrathoracic or cervical anastomosis in a single center
      study. METHODS: 72 patients who received either a cervical or intrathoracic
      anastomosis after esophageal resection for esophageal cancer were matched by age
      and tumor stage. Collected data from these patients were analyzed retrospectively
      regarding morbidity and mortality rates. RESULTS: Anastomotic leakage rate was
      significantly lower in the intrathoracic anastomosis group than in the cervical
      anastomosis group (4 of 36 patients (11%) vs. 11 of 36 patients (31%); p =
      0.040). The hospital stay was significantly shorter in the intrathoracic
      anastomosis group compared to the cervical anastomosis group (14 (range 10-110)
      vs. 26 days (range 12 - 105); p = 0.012). Wound infection and temporary paresis
      of the recurrent laryngeal nerve occurred significantly more often in the
      cervical anastomosis group compared to the intrathoracic anastomosis group (28%
      vs. 0%; p = 0.002 and 11% vs. 0%; p = 0.046). The overall In-hospital mortality
      rate was 6% (4 of 72 patients) without any differences between the study groups.
      CONCLUSIONS: The present data support the assumption that the transthoracic
      approach with an intrathoracic anastomosis compared to a cervical
      esophagogastrostomy is the safer and more beneficial procedure in patients with
      carcinoma of the lower and middle third of the esophagus due to a significant
      reduction of anastomotic leakage, wound infection, paresis of the recurrent
      laryngeal nerve and shorter hospital stay.

PMID- 22866814
TI  - Loss of muscleblind-like 1 promotes invasive mesenchyme formation in endocardial
      cushions by stimulating autocrine TGFbeta3.
AB  - BACKGROUND: Valvulogenesis and septation in the developing heart depend on the
      formation and remodeling of endocardial cushions in the atrioventricular canal
      (AVC) and outflow tract (OFT). These cushions are invaded by a subpopulation of
      endocardial cells that undergo an epithelial-mesenchymal transition in response
      to paracrine and autocrine transforming growth factor beta (TGFbeta) signals. We
      previously demonstrated that the RNA binding protein muscleblind-like 1 (MBNL1)
      is expressed specifically in the cushion endocardium, and knockdown of MBNL1 in
      stage 14 embryonic chicken AVC explants enhances TGFbeta-dependent endocardial
      cell invasion. RESULTS: In this study, we demonstrate that the effect of MBNL1
      knockdown on invasion remains dependent on TGFbeta3 after it is no longer
      required to induce basal levels of invasion. TGFbeta3, but not TGFbeta2, levels
      are elevated in medium conditioned by MBNL1-depleted AVC explants. TGFbeta3 is
      elevated even when the myocardium is removed, indicating that MBNL1 modulates
      autocrine TGFbeta3 production in the endocardium. More TGFbeta3-positive cells
      are observed in the endocardial monolayer following MBNL1 knockdown. Addition of
      exogenous TGFbeta3 to AVC explants recapitulates the effects of MBNL1 knockdown.
      Time course experiments demonstrate that knockdown of MBNL1 induces precocious
      TGFbeta3 secretion, and early exposure to excess TGFbeta3 induces precocious
      invasion. MBNL1 expression precedes TGFbeta3 in the AVC endocardium, consistent
      with a role in preventing precocious autocrine TGFbeta3 signaling. The
      stimulatory effects of MBNL1 knockdown on invasion are lost in stage 16 AVC
      explants. Knockdown of MBNL1 in OFT explants similarly enhances cell invasion,
      but not activation. TGFbeta is necessary and sufficient to mediate this effect.
      CONCLUSIONS: Taken together, these data support a model in which MBNL1 negatively
      regulates cell invasion in the endocardial cushions by restricting the magnitude
      and timing of endocardial-derived TGFbeta3 production.

PMID- 22866815
TI  - Fabrication of a composite colloidal particle with unusual Janus structure as a
      high-performance solid emulsifier.
AB  - Core-shell particles with cross-linked core and shell were used as seed particles
      to produce composite Janus particles. It was found that when the shell has
      distinctly higher cross-linking degree than the core, Janus particles with very
      unusual structures can be obtained. These particles have two parts, with one part
      embraced partially or entirely by the other part, adjustable by parameters such
      as phase ratio or cross-linking degree. On the basis of experimental
      observations, a possible mechanism for the formation of such unusual Janus
      particles has been proposed. Janus particles with arms are used to emulsify water
      toluene mixtures, forming oil-in-water (O/W) emulsions at very high internal
      phase content with rather low concentration of particles. Nonspherical emulsion
      droplets were observed, indicating that these Janus particles are likely to jam
      at the interface, forming a strong protecting layer to stabilize emulsions.

PMID- 22866817
TI  - How can student experience enhance the development of a model of
      interprofessional clinical skills education in the practice placement setting?
AB  - The practice placement setting offers opportunities and challenges for engaging
      students in high-quality interprofessional learning. The Fife Interprofessional
      Clinical Skills Model for Education was established to develop structured
      interprofessional learning opportunities for students during their clinical
      attachments in NHS Fife. This short report describes the delivery and evaluation
      of the model, which was piloted with students from the nursing, medicine and
      allied health professions. Scheduled workshops were delivered within primary and
      secondary care locations. The learning activities involved exploring and
      comparing their professional identities, discussing roles and responsibilities
      within the healthcare team and practicing nontechnical clinical skills. Students
      who participated in the workshops reported that they developed a better
      understanding of each other's roles and responsibilities and also identified that
      this would be transferable knowledge to their future practice. Exploring the
      student experience has assisted in developing relevant and accessible
      interprofessional learning opportunities within the practice placement setting.

PMID- 22866816
TI  - The effect of spinal manipulative therapy on spinal range of motion: a systematic
      literature review.
AB  - BACKGROUND: Spinal manipulative therapy (SMT) has been shown to have an effect on
      spine-related pain, both clinically and in experimentally induced pain. However,
      it is unclear if it has an immediate noticeable biomechanical effect on spinal
      motion that can be measured in terms of an increased range of motion (ROM).
      OBJECTIVE: To assess the quality of the literature and to determine whether or
      not SMT is associated with an immediate increase in ROM. DESIGN: A systematic
      critical literature review. METHOD: Systematic searches were performed in Pubmed,
      the Cochrane Library and EMBASE using terms relating to manipulation, movement
      and the spine. Selection of articles was made according to specific criteria by
      two independent reviewers. Two checklists were created based on the needs of the
      present review. Articles were independently reviewed by two reviewers. Articles
      were given quality scores and the data synthesized for each region treated in the
      literature. Findings were summarized in tables and reported in a narrative
      fashion. RESULTS: Fifteen articles were retained reporting on experiments on the
      neck, lumbar spine, hip and jaw. The mean quality score was 71/100 (ranges 33/100
      - 92/100). A positive effect of SMT was reported in both studies where mouth
      opening was assessed after cervical manipulation. In five of the nine studies on
      cervical ROM a positive effect was reported, whereas the remaining four studies
      did not show improvement. None of the three studies of the lumbar spine showed an
      effect of SMT on lumbar ROMs and one study of sacroiliac manipulation reported no
      effect on the ROM of the hip joint.In relation to the quality score, the seven
      highest ranked studies, showed significant positive effects of SMT on ROM.
      Continuing down the list, the other studies reported no significant differences
      in the outcomes between groups. CONCLUSION: SMT seems sometimes to have a small
      effect on ROM, at least in the cervical spine. Further research should
      concentrate on areas of the spine that have the potential of actually improving
      to such a degree that a change can be easily uncovered.

PMID- 22866818
TI  - "Let's stick together"--a grounded theory exploration of interprofessional
      working used to provide person centered chronic back pain services.
AB  - Chronic back pain is a global phenomenon and a common reason why patients seek
      help from health professionals. Person-centered interprofessional working is
      acknowledged as the main strategy for chronic back pain management; however, the
      complexity of chronic pain can present significant challenges for teams. Although
      methods used by interprofessional teams to collaborate have been previously
      explored, how they work together to deliver person-centered chronic back pain
      care has received limited attention. The aim of this study was to explore person
      centered care from the perspectives of people with chronic back pain and the
      interprofessional teams who cared for them. A grounded theory methodology was
      used to capture the interprofessional team's perspectives of person-centered
      working. A purposive sample of four chronic back pain management teams
      participated in semi-structured face-to-face interviews and focus groups. Data
      were thematically analyzed using a constant comparative method. Three categories
      emerged, collective efficacy, negotiated space and team maturity, which
      illustrated the attributes of interprofessional teams that influenced person
      centered working. The findings suggest that collective efficacy matures over time
      within a negotiated coalesced space and re-enforces the need for teams to stick
      together to ensure effective person-centered care.

PMID- 22866819
TI  - An exploration of the experiences of recent graduates from an interprofessional
      foundation degree.
AB  - This short report describes a study which aimed to explore the experiences of
      newly qualified assistant practitioners (APs) from an interprofessional
      foundation degree in long-term conditions. Interviews were carried out with one
      cohort of newly qualified APs and their employee mentors, 6-9 months after the
      APs had re-entered full-time practice. Three major themes were identified after
      analysis of the interview transcripts: widened AP horizons, poor AP pay and
      conditions and friction between APs and their colleagues. The course was highly
      praised by the APs and their workplace mentors. Unfortunately, the workplace
      infrastructure needed to support the APs was reported to be inadequate.

PMID- 22866820
TI  - Opposing effects of Notch-signaling in maintaining the proliferative state of
      follicle cells in the telotrophic ovary of the beetle Tribolium.
AB  - INTRODUCTION: Establishment of distinct follicle cell fates at the early stages
      of Drosophila oogenesis is crucial for achieving proper morphology of individual
      egg chambers. In Drosophila oogenesis, Notch-signaling controls proliferation and
      differentiation of follicular cells, which eventually results in the polarization
      of the anterior-posterior axis of the oocyte. Here we analyzed the functions of
      Tribolium Notch-signaling factors during telotrophic oogenesis, which differs
      fundamentally from the polytrophic ovary of Drosophila. RESULTS: We found Notch
      signaling to be required for maintaining the mitotic cycle of somatic follicle
      cells. Upon Delta RNAi, follicle cells enter endocycle prematurely, which affects
      egg-chamber formation and patterning. Interestingly, our results indicate that
      Delta RNAi phenotypes are not solely due to the premature termination of cell
      proliferation. Therefore, we monitored the terminal/stalk cell precursor lineage
      by molecular markers. We observed that upon Delta RNAi terminal and stalk cell
      populations were absent, suggesting that Notch-signaling is also required for the
      specification of follicle cell populations, including terminal and stalk
      precursor cells. CONCLUSIONS: We demonstrate that with respect to mitotic
      cycle/endocycle switch Notch-signaling in Tribolium and Drosophila has opposing
      effects. While in Drosophila a Delta-signal brings about the follicle cells to
      leave mitosis, Notch-signaling in Triboliumis necessary to retain telotrophic egg
      chambers in an "immature" state. In most instances, Notch-signaling is involved
      in maintaining undifferentiated (or preventing specialized) cell fates. Hence,
      the role of Notch in Tribolium may reflectthe ancestral function of Notch
      signaling in insect oogenesis.The functions of Notch-signaling in patterning the
      follicle cell epithelium suggest that Tribolium oogenesis may - analogous to
      Drosophila - involve the stepwise determination of different follicle cell
      populations. Moreover, our results imply that Notch-signaling may contribute at
      least to some aspects of oocyte polarization and AP axis also in telotrophic
      oogenesis.

PMID- 22866821
TI  - Comparative evaluation of treatment with low-dose aspirin plus dipyridamole
      versus aspirin only in patients with acute ischaemic stroke.
AB  - BACKGROUND: Previous studies have suggested that pre-stroke treatment with low
      dose aspirin (A) could reduce the severity of acute ischaemic stroke, but less is
      known on the effect of pre-stroke treatment with a combination of aspirin and
      dipyridamole (A + D) and post-stroke effects of these drugs. The aim of the
      present study was to evaluate the effect of this drug combination on acute and
      long-term prognosis of ischaemic stroke. METHODS: Patients without atrial
      fibrillation admitted to the stroke unit with acute ischaemic stroke (n = 554) or
      TIA (n = 108) were studied during acute hospital care and up to 12 months after
      discharge from hospital. RESULTS: Prior to acute stroke 62 patients were treated
      with A + D while 247 patients were treated with A only. No beneficial effects of
      the combination A + D compared to A only were noted on stroke severity and/or
      acute in-hospital mortality. However, survival analysis by Cox-proportional
      hazard model demonstrated lower 12-months all-cause mortality in patients
      discharged with A + D (n = 275) compared with patients on A only (HR, 0.52; CI,
      0.32-0.86; p = 0.011; n = 262) after adjusting for age, baseline NIHSS, previous
      stroke, previous myocardial infarction and type 2 diabetes. We also noted a
      tendency towards lower all-cause mortality at 3 months with use of A + D, but
      this was not statistically significant (p = 0.12). CONCLUSIONS: Pre-stroke
      treatment with a combination of low-dose A + D does not reduce the severity of
      acute stroke, nor does it reduce the acute in-hospital mortality. However,
      treatment with A + D at discharge from hospital is seemingly associated with
      lower long-term mortality compared with A only, contrary to the results from
      previous randomised studies. However, our results must be interpreted with
      extreme caution considering the non-randomised study design.

PMID- 22866822
TI  - Engaging with research ethics in central Francophone Africa: reflections on a
      workshop about ancillary care.
AB  - Research ethics is predominantly taught and practiced in Anglophone countries,
      particularly those in North America and Western Europe. Initiatives to build
      research ethics capacity in developing countries must attempt to avoid imposing
      foreign frameworks and engage with ethical issues in research that are locally
      relevant. This article describes the process and outcomes of a capacity-building
      workshop that took place in Kinshasa, Democratic Republic of Congo in the summer
      of 2011. Although the workshop focused on a specific ethical theme - the
      responsibilities of researchers to provide health-related care to their research
      participants - we argue that the structure of the workshop offers a useful method
      for engaging with research ethics in general, and the theme of ancillary care
      encourages a broad perspective on research ethics that is highly pertinent in low
      income countries. The workshop follows an interactive, locally driven model that
      could be fruitfully replicated in similar settings.

PMID- 22866823
TI  - 185 nm photoreduction of CO2 to methane by water. Influence of the presence of a
      basic catalyst.
AB  - Photolysis of CO(2) at 185 nm using a Hg lamp in the presence of H(2) or H(2)O
      leads to the formation of CH(4) (after an induction period) and a lesser amount
      of CO. Using H(2) gas as reducing agent, up to 40% conversion was achieved with
      almost complete selectivity to methane and energy consumption of 1.55 Gcal/mol.
      When CO(2) irradiation is carried out in the gas phase in the presence of H(2)O,
      both reagents can undergo photolysis, and H(2) generation from water is a
      competing process accompanying the formation of CO and CH(4) (CO(2) conversion
      0.67% at 14 h). For the irradiation of CO(2) using H(2)O as reducing agent, basic
      solids (K(+)-exchanged Y zeolite or hydrotalcites) can increase CO(2) conversion
      up to 2.21% with total selectivity toward CH(4) and an energy consumption of 4.5
      Gcal/mol. This result opens a door in the quest for efficient photocatalysts that
      could further increase the apparent quantum yield of the process, particularly at
      longer wavelengths.

PMID- 22866824
TI  - Development and validation of a clinical prediction rule for chest wall syndrome
      in primary care.
AB  - BACKGROUND: Chest wall syndrome (CWS), the main cause of chest pain in primary
      care practice, is most often an exclusion diagnosis. We developed and evaluated a
      clinical prediction rule for CWS. METHODS: Data from a multicenter clinical
      cohort of consecutive primary care patients with chest pain were used (59 general
      practitioners, 672 patients). A final diagnosis was determined after 12 months of
      follow-up. We used the literature and bivariate analyses to identify candidate
      predictors, and multivariate logistic regression was used to develop a clinical
      prediction rule for CWS. We used data from a German cohort (n = 1212) for
      external validation. RESULTS: From bivariate analyses, we identified six
      variables characterizing CWS: thoracic pain (neither retrosternal nor
      oppressive), stabbing, well localized pain, no history of coronary heart disease,
      absence of general practitioner's concern, and pain reproducible by palpation.
      This last variable accounted for 2 points in the clinical prediction rule, the
      others for 1 point each; the total score ranged from 0 to 7 points. The area
      under the receiver operating characteristic (ROC) curve was 0.80 (95% confidence
      interval 0.76-0.83) in the derivation cohort (specificity: 89%; sensitivity: 45%;
      cut-off set at 6 points). Among all patients presenting CWS (n = 284), 71% (n =
      201) had a pain reproducible by palpation and 45% (n = 127) were correctly
      diagnosed. For a subset (n = 43) of these correctly classified CWS patients, 65
      additional investigations (30 electrocardiograms, 16 thoracic radiographies, 10
      laboratory tests, eight specialist referrals, one thoracic computed tomography)
      had been performed to achieve diagnosis. False positives (n = 41) included three
      patients with stable angina (1.8% of all positives). External validation revealed
      the ROC curve to be 0.76 (95% confidence interval 0.73-0.79) with a sensitivity
      of 22% and a specificity of 93%. CONCLUSIONS: This CWS score offers a useful
      complement to the usual CWS exclusion diagnosing process. Indeed, for the 127
      patients presenting CWS and correctly classified by our clinical prediction rule,
      65 additional tests and exams could have been avoided. However, the reproduction
      of chest pain by palpation, the most important characteristic to diagnose CWS, is
      not pathognomonic.

PMID- 22866825
TI  - Self-monitoring of blood glucose: guideline application rather than utilization
      restrictions on testing strips has potential to reduce diabetes healthcare costs
      in Italy.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) is a proven tool to improve
      glycemic control, even if it might increase direct costs for diabetes management.
      In Italy, the purchase, prescription rules and responsibilities, and distribution
      of testing strips per type of patient are managed differently in each of the 20
      Italian regions. The Italian scientific societies for diabetes (Societa Italiana
      Diabetologia [SID] and Associazione Medici Diabetologi [AMD]) have issued
      validated guidelines for SMBG, but not all regions apply them. We investigated
      whether following SID-AMD guidelines would help decreasing SMBG and diabetes
      healthcare costs in Italy. MATERIALS AND METHODS: We compared the regions
      applying and not applying SMBG guidelines for the mean number of testing strips
      used, number of hospitalizations (with the principal diagnosis of diabetes,
      excluding diabetes complications), and duration of hospitalization, as indirect
      measures of SMBG cost. RESULTS: Regions applying the guidelines recorded higher
      SMBG testing strip utilization than regions not applying guidelines, but they
      recorded fewer hospitalizations for diabetes (36.2 +/- 11.3 vs. 79.9 +/- 27.8
      hospitalizations per 100,000 inhabitants, P<0.002) and fewer days in the hospital
      (363 +/- 106 vs. 685 +/- 194 days of hospitalization for diabetes per 100,000
      inhabitants, P<0.002). CONCLUSIONS: Our data suggest that application of
      guidelines for SMBG prescription and a strict cooperation between health
      providers and regional health economic deciders were associated with greater
      utilization of SMBG testing strips. They were also associated with significantly
      reduced number of hospitalizations and reduced overall duration of
      hospitalization for patients with diabetes, potentially saving healthcare costs.

PMID- 22866826
TI  - Tumor budding as a risk factor of lymph node metastasis in submucosal invasive T1
      colorectal carcinoma: a retrospective study.
AB  - BACKGROUND: This study was designed to identify risk factors for lymph node
      metastasis of early stage colorectal cancer, which was confirmed to a carcinoma
      that invaded the submucosa after radical resection. METHODS: In total, 55
      patients revealing submucosal invasive colorectal carcinoma on pathology who
      underwent curative radical resection at the Department of Surgery, St. Vincent's
      Hospital, The Catholic University of Korea from January 2007 to September 2010
      were evaluated retrospectively. Tumor size, depth of submucosal invasion,
      histologic grade, lymphovascular invasion, tumor budding, and microacinar
      structure were reviewed by a single pathologist. Student t-test for continuous
      variables and Chi-square test for categorical variables were used for comparing
      the clinicopathological features between two groups (whether lymph node
      involvement existed or not). Continuous variables are expressed as the mean +/-
      standard error while statistical significance is accepted at P < 0.05. RESULTS:
      The mean age of 55 patients (34 males and 21 females) was 61.2 +/- 9.6 years
      (range, 43-83). Histologically, eight (14.5%) patients had metastatic lymph node.
      In the univariate analysis, tumor budding (P = 0.047) was the only factor that
      was significantly associated with lymph node metastasis. Also, the tumor budding
      had a sensitivity of 83.3%, a specificity of 60.5%, and a negative predictive
      value of 0.958 for lymph node metastasis in submucosal invasive T1 colorectal
      cancer. CONCLUSIONS: The tumor budding seems to have a high sensitivity (83.3%),
      acceptable specificity (60.5%), and a high negative predictive value (0.958). A
      close examination of pathologic finding including tumor budding should be
      performed in order to manage early CRC properly.

PMID- 22866827
TI  - Frequency of occurrence and potency range distribution of activity cliffs in
      bioactive compounds.
AB  - We have systematically identified activity cliffs in bioactive compounds for
      which high-confidence potency data were available. Different molecular
      representations were utilized and similarity and potency difference criteria for
      activity cliffs were clearly defined. Cliff formation was studied across the
      global potency range observed for qualifying bioactive compounds. Depending on
      the specific representation of activity cliffs, between ~22% and 34% of all
      active compounds meeting the data selection criteria were involved in the
      formation of at least one activity cliff spanning a potency difference of at
      least two orders of magnitude. However, these cliffs involved only between ~4.7%
      and ~5.7% of all compound pairs meeting the similarity criteria. Hence, in light
      of these findings, the formation of well-defined activity cliffs is a relatively
      rare event. Moreover, the potency range distribution of activity cliffs was
      analyzed in detail, revealing that most activity cliffs were formed between
      compounds with micro- and nanomolar potency, consistent with the global
      distribution of potency data. On the basis of our analysis, we propose a general
      definition of activity cliffs for data mining.

PMID- 22866828
TI  - Continuous multiple liquid-liquid separation: diazotization of amino acids in
      flow.
AB  - A second-generation laboratory-scale, modular liquid-liquid separation device
      based on computer-controlled high-pressure pumps and a high-resolution digital
      camera has been invented. The diazotization of amino acids to produce valuable
      chiral hydroxyacids is demonstrated in flow for the first time. The use of a
      triple-separator system in conjuction with the developed diazotization process
      allows the safe and efficient production and automated isolation of multigram
      quantities of valuable chiral hydroxyacids.

PMID- 22866829
TI  - Optical properties of triplex DNA from time-dependent density functional theory.
AB  - We present a combined investigation of the dynamics and optics of triplex DNA,
      based on classical molecular dynamics and time-dependent density functional
      theory. Our approach is devised to include the effects of conformational
      fluctuations on the electronic structure and optical excitations of the system.
      We find that the structural flexibility has a strong role in the determination of
      the optical signals. Our results allow us to unravel the peculiar fingerprints of
      Watson-Crick and Hoogsteen H-bonding in the optical absorption spectra. We find a
      specific optical absorption feature that is due to the simultaneous presence of
      the two H-bonding patterns in C(+)GC triplets. While this peculiar triplet signal
      is wiped out in some structures that are representative of the finite-temperature
      dynamics, it can be recovered in an average view, so that it is a pristine result
      of this work.

PMID- 22866830
TI  - Associations between family structure changes and children's behavior problems:
      the moderating effects of timing and marital birth.
AB  - Most children in the U.S. today will experience one or more changes in family
      structure. The present study explores the implications of this trend for child
      development by investigating the conditions under which family structure changes
      matter most to child well-being. Using data from the Maternal and Child
      Supplement of the National Longitudinal Survey of Youth (N = 3,492), it estimates
      how changes in family structure experienced during 4 different developmental
      periods relate to concurrent and subsequent changes in children's behavioral
      trajectories. We estimate associations separately for children born to married
      and unwed parents to determine whether family instability has different
      associations with children's behavior across policy-relevant family types.
      Results indicate that changes in family structure during the first 3 years of
      life predict children's behavioral development more consistently than later
      changes, changes into a single-parent family have different implications for
      children's development than changes into a blended family, and changes in family
      structure matter more for children born to married parents than children born to
      unwed parents. (PsycINFO Database Record (c) 2013 APA, all rights reserved). 

PMID- 22866831
TI  - Philosophy, dogma, and possibilities.

PMID- 22866865
TI  - Cellulose nanocrystal-assisted dispersion of luminescent single-walled carbon
      nanotubes for layer-by-layer assembled hybrid thin films.
AB  - Highly stable single-walled carbon nanotube (SWNT) dispersions are obtained after
      ultrasonication in cellulose nanocrystal (CN) aqueous colloidal suspensions. Mild
      dispersion conditions were applied to preserve the SWNT length in order to
      facilitate the identification of hybrid objects. This led to a moderate
      dispersion of 24% of the SWNTs. Under these conditions, atomic force microscopy
      (AFM) and transmission electron microscopy (TEM) experiments succeeded in
      demonstrating the formation of hybrid particles in which CNs are aligned along
      the nanotube axis by a self-assembly process. These SWNT/CN dispersions are used
      to create multilayered thin films with the layer-by-layer method using
      polyallylamine hydrochloride as a polyelectrolyte. Homogeneous films from one to
      eight bilayers are obtained with an average bilayer thickness of 17 nm. The
      presence of SWNTs in each bilayer is attested to by characteristic Raman signals.
      It should be noted that these films exhibit a near-infrared luminescence signal
      due to isolated and well-separated nanotubes. Furthermore, scanning electron
      microscopy (SEM) suggests that the SWNT network is percolating through the film.

PMID- 22866866
TI  - Does anti-malarial drug knowledge predict anti-malarial dispensing practice in
      drug outlets? A survey of medicine retailers in western Kenya.
AB  - BACKGROUND: Malaria is a major cause of morbidity and mortality in Kenya, where
      it is the fifth leading cause of death in both children and adults. Effectively
      managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to
      83 percent of febrile individuals first seek treatment for febrile illness over
      the counter from medicine retailers. Understanding medicine retailer knowledge
      and behaviour in treating suspected malaria and dispensing anti-malarials is
      crucial. METHODS: To investigate medicine retailer knowledge about anti-malarials
      and their dispensing practices, a survey was conducted of all retail drug outlets
      that sell anti-malarial medications and serve residents of the Webuye Health and
      Demographic Surveillance Site in the Bungoma East District of western Kenya.
      RESULTS: Most of the medicine retailers surveyed (65%) were able to identify
      artemether-lumefantrine (AL) as the Kenyan Ministry of Health recommended first
      line anti-malarial therapy for uncomplicated malaria. Retailers who correctly
      identified this treatment were also more likely to recommend AL to adult and
      paediatric customers. However, the proportion of medicine retailers who recommend
      the correct treatment is disappointingly low. Only 48% would recommend AL to
      adults, and 37% would recommend it to children. It was discovered that customer
      demand has an influence on retailer behaviour. Retailer training and education
      were found to be correlated with anti-malarial drug knowledge, which in turn is
      correlated with dispensing practices. Medicine retailer behaviour, including
      patient referral practice and dispensing practices, are also correlated with
      knowledge of the first-line anti-malarial medication. The Kenya Ministry of
      Health guidelines were found to influence retailer drug stocking and dispensing
      behaviours. CONCLUSION: Most medicine retailers could identify the recommended
      first-line treatment for uncomplicated malaria, but the percentage that could not
      is still too high. Furthermore, knowing the MOH recommended anti-malarial
      medication does not always ensure it is recommended or dispensed to customers.
      Retailer training and education are both areas that could be improved.
      Considering the influence that patient demand has on retailer behaviour, future
      interventions focusing on community education may positively influence
      appropriate dispensing of anti-malarials.

PMID- 22866867
TI  - The tumor suppressor gene RBM5 inhibits lung adenocarcinoma cell growth and
      induces apoptosis.
AB  - BACKGROUND: The loss of tumor suppressor gene (TSG) function is a critical step
      in the pathogenesis of human lung cancer. RBM5 (RNA-binding motif protein 5, also
      named H37/LUCA-15) gene from chromosome 3p21.3 demonstrated tumor suppressor
      activity. However, the role of RBM5 played in the occurrence and development of
      lung cancer is still not well understood. METHOD: Paired non-tumor and tumor
      tissues were obtained from 30 adenocarcinomas. The expression of RBM5 mRNA and
      protein was examined by RT-PCR and Western blot. A549 cell line was used to
      determine the apoptotic function of RBM5 in vitro. A549 cells were transiently
      transfected with pcDNA3.1-RBM5. AnnexinV analysis was performed by flow
      cytometry. Expression of Bcl-2, cleaved caspase-3, caspase-9 and PAPP proteins in
      A549 lung cancer cells and the A549 xenograft BALB/c nude mice model was
      determined by Western blot. Tumor suppressor activity of RBM5 was also examined
      in the A549 xenograft model treated with pcDNA3.1-RBM5 plasmid carried by
      attenuated Salmonella typhi Ty21a. RESULT: The expression of RBM5 mRNA and
      protein was decreased significantly in adenocarcinoma tissues compared to that in
      the non-tumor tissues. In addition, as compared to the vector control, a
      significant growth inhibition of A549 lung cancer cells was observed when
      transfected with pcDNA3.1-RBM5 as determined by cell proliferation assay. We also
      found that overexpression of RBM5 induced both early and late apoptosis in A549
      cells using AnnexinV/PI staining as determined by flow cytometry. Furthermore,
      the expression of Bcl-2 protein was decreased, whereas the expression of cleaved
      caspase-3, caspase-9 and PARP proteins was significantly increased in the RBM5
      transfected cells; similarly, expression of decreased Bcl-2 and increased cleaved
      caspase-3 proteins was also examined in the A549 xenograft model. More
      importantly, we showed that accumulative and stable overexpression of RBM5 in the
      A549 xenograft BALB/c nude mice model significantly inhibited the tumor growth
      rate in vivo as compared to that in the control. CONCLUSION: Our study
      demonstrates that RBM5 can inhibit the growth of lung cancer cells and induce
      apoptosis both in vitro and in vivo, which suggests that RBM5 might be used as a
      potential biomarker or target for lung cancer diagnosis and chemotherapy.
      Moreover, we propose a novel animal model set up in BALB/c nude mice treated with
      attenuated Salmonella as a vector carrying plasmids to determine RBM5 function in
      vivo.

PMID- 22866868
TI  - Genetic diversity in Capsicum baccatum is significantly influenced by its
      ecogeographical distribution.
AB  - BACKGROUND: The exotic pepper species Capsicum baccatum, also known as the aji or
      Peruvian hot pepper, is comprised of wild and domesticated botanical forms. The
      species is a valuable source of new genes useful for improving fruit quality and
      disease resistance in C. annuum sweet bell and hot chile pepper. However,
      relatively little research has been conducted to characterize the species, thus
      limiting its utilization. The structure of genetic diversity in a plant germplasm
      collection is significantly influenced by its ecogeographical distribution.
      Together with DNA fingerprints derived from AFLP markers, we evaluated variation
      in fruit and plant morphology of plants collected across the species native range
      in South America and evaluated these characters in combination with the unique
      geography, climate and ecology at different sites where plants originated.
      RESULTS: The present study mapped the ecogeographic distribution, analyzed the
      spatial genetic structure, and assessed the relationship between the spatial
      genetic pattern and the variation of morphological traits in a diverse C.
      baccatum germplasm collection spanning the species distribution. A combined
      diversity analysis was carried out on the USDA-ARS C. baccatum germplasm
      collection using data from GIS, morphological traits and AFLP markers. The
      results demonstrate that the C. baccatum collection covers wide geographic areas
      and is adapted to divergent ecological conditions in South America ranging from
      cool Andean highland to Amazonia rainforest. A high level of morphological
      diversity was evident in the collection, with fruit weight the leading variable.
      The fruit weight distribution pattern was compatible to AFLP-based clustering
      analysis for the collection. A significant spatial structure was observed in the
      C. baccatum gene pool. Division of the domesticated germplasm into two major
      regional groups (Western and Eastern) was further supported by the pattern of
      spatial population structure. CONCLUSIONS: The results reported improve our
      understanding of the combined effects of geography, ecology and human
      intervention on organization of the C. baccatum genepool. The results will
      facilitate utilization of C. baccatum for crop improvement and species
      conservation by providing a framework for efficient germplasm collection
      management and guidance for future plant acquisitions.

PMID- 22866869
TI  - Wealth and antenatal care use: implications for maternal health care utilisation
      in Ghana.
AB  - The study investigates the effect of wealth on maternal health care utilization
      in Ghana via its effect on Antenatal care use. Antenatal care serves as the
      initial point of contact of expectant mothers to maternal health care providers
      before delivery. The study is pivoted on the introduction of the free maternal
      health care policy in April 2005 in Ghana with the aim of reducing the financial
      barrier to the use of maternal health care services, to help reduce the high rate
      of maternal deaths. Prior to the introduction of the policy, studies found wealth
      to have a positive and significant influence on the use of Antenatal care. It is
      thus expected that with the policy, wealth should not influence the use of
      maternal health care significantly. Using secondary data from the 2008 Ghana
      Demographic and Health survey, the results have revealed that wealth still has a
      significant influence on adequate use of Antenatal care. Education, age, number
      of living children, transportation and health insurance are other factors that
      were found to influence the use of Antenatal care in Ghana. There also exist
      considerable variations in the use of Antenatal care in the geographical regions
      and between the rural and urban dwellers. It is recommended that to improve the
      use of Antenatal care and hence maternal health care utilization, some means of
      support is provided especially to women within the lowest wealth quintiles, like
      the provision and availability of recommended medication at the health center;
      secondly, women should be encouraged to pursue education to at least the
      secondary level since this improves their use of maternal health services. Policy
      should also target mothers who have had the experience of child birth on the need
      to use adequate Antenatal care for each pregnancy, since these mothers tend to
      use less antenatal care for subsequent pregnancies. The regional disparities
      found may be due to inaccessibility and unavailability of health facilities and
      services in the rural areas and in some of the regions. The government and other
      service providers (NGOs, religious institutions and private providers) may
      endeavor to improve on the distribution of health facilities, human resources,
      good roads and necessary infrastructure among other things in order to facilitate
      easy access to health care providers especially for the rural dwellers.

PMID- 22866870
TI  - Morphological and crystalline evolution of nanostructured MnO2 and its
      application in lithium--air batteries.
AB  - Single-crystal alpha-MnO(2) nanotubes have been successfully synthesized by
      microwave-assisted hydrothermal of potassium permanganate in the presence of
      hydrochloric acid. The growth mechanism including the morphological and
      crystalline evolution has been carefully studied with time-dependent X-ray
      diffraction, electron microscopy, and controlled synthesis. The as-synthesized
      MnO(2) nanostructures are incorporated in air cathodes of lithium--air batteries
      as electrocatalysts for the oxygen reduction and evolution reactions. The
      characterization reveals that the electrodes made of single-crystalline alpha
      MnO(2) nanotubes exhibit much better stability than those made of alpha-MnO(2)
      nanowires and delta-MnO(2) nanosheet-based microflowers in both charge and
      discharge processes.

PMID- 22866871
TI  - Low molecular weight components in an aquatic humic substance as characterized by
      membrane dialysis and orbitrap mass spectrometry.
AB  - Suwannee River fulvic acid (SRFA) was dialyzed through a 100-500 molecular weight
      cutoff dialysis membrane, and the dialysate and retentate were analyzed by UV
      visible absorption and high-resolution Orbitrap mass spectrometry (MS). A
      significant fraction (36% based on dissolved organic carbon) of SRFA passed
      through the dialysis membrane. The fraction of SRFA in the dialysate had a
      different UV-visible absorption spectrum and was enriched in low molecular weight
      molecules with a more aliphatic composition relative to the initial SRFA
      solution. Comparison of the SRFA spectra collected by Orbitrap MS and Fourier
      transform ion cyclotron resonance MS (FT-ICR MS) demonstrated that the mass
      accuracy of the Orbitrap MS is sufficient for determination of unique molecular
      formulas of compounds with masses <600 Da in a complex mixture, such as SRFA. The
      most intense masses detected by Orbitrap MS were found in the 100-200 Da mass
      range. Many of these low molecular masses corresponded to molecular formulas of
      previously identified compounds in organic matter, lignin, and plants, and the
      use of the standard addition method provided an upper concentration estimate of
      selected target compounds in SRFA. Collectively, these results provide evidence
      that SRFA contains low molecular weight components that are present individually
      or in loosely bound assemblies.

PMID- 22866872
TI  - Increased left anterior insular and inferior prefrontal activity in post-stroke
      mania.
AB  - BACKGROUND: Post-stroke mania is an infrequent complication after stroke, and the
      mechanisms underlying this disorder remain unclear. Although a contralesional
      release phenomenon has been implicated in post-stroke mania, empirical findings
      are lacking. CASE PRESENTATION: We present a case report of post stroke mania.
      Single photon emission tomography (SPECT) was performed twice, during the manic
      state and during the remitted euthymic state. The first SPECT study performed
      during the manic state demonstrated hypoperfusion in the right temporal and
      frontal regions due to right putaminal hemorrhage. It also showed hyperperfusion
      in the inferior lateral prefrontal lobe, the temporal lobe, and the medial and
      lateral parts of the parietal lobe in the left hemisphere. The second SPECT study
      performed during the euthymic state demonstrated moderate improvement in the
      hypoperfusion in the right fronto-temporal regions. Furthermore, compared to the
      findings on the first SPECT study, the second study showed that the focal
      hyperperfusion in the anterior insular cortex, inferior lateral prefrontal lobes,
      and superior-middle temporal gyrus in the left hemisphere had vanished.
      CONCLUSION: Increased left inferior prefrontal and anterior insular activity and
      reduced extensive right fronto-temporal lobe activity are involved in the
      development of post-stroke mania.

PMID- 22866873
TI  - Toward crystalline molecular rotors with linearly conjugated diethynyl-phenylene
      rotators and pentiptycene stators.
AB  - A strategy for the construction of crystalline molecular rotors involves the
      assemblage of chemical structures that emulate the elements of macroscopic rotary
      devices, such as those found in macroscopic gyroscopes and compasses. In this
      report, we describe an efficient and short synthetic route for preparation of
      molecular rotors with two pentiptycene-units linked at their central benzene ring
      by triple bonds to a linearly conjugated phenylene rotator. Five analogous
      compounds with phenol, alkoxy, or alkoxycarbonyl substituents were synthesized
      and fully characterized in solution and in the solid-state through various
      methods, such as cross-polarization magic angle spinning (CPMAS) (13)C NMR and
      single crystal X-ray diffraction. Molecular and packing structures obtained from
      single crystal X-ray diffraction and crystallization properties were analyzed
      with the goal of identifying the key parameters that may hinder or facilitate the
      formation of dynamically functional, crystalline molecular rotors.

PMID- 22866874
TI  - Evaluation of the value of calcium to creatinine ratio for predicting of pre
      eclampsia.
AB  - INTRODUCTION: Pre-eclampsia is one of the most serious complications in pregnancy
      and is one of the major causes of maternal death. Therefore, its prediction has
      special importance and many studies have been performed on different materials,
      which may be useful for its prediction. OBJECTIVE: The purpose of the present
      study is to evaluate the calcium to creatinine ratio for the prediction of pre
      eclampsia. METHOD: A prospective cohort study was performed on 150 pregnant
      women, who were aged from 15 to 35 years. A single urine sample was obtained at
      20-24 weeks of gestation for measurement of urine calcium to creatinine ratio.
      The women were then monitored for delivery and this ratio was compared between
      the women with and without pre-eclampsia. RESULTS: Mean urine calcium of pre
      eclamptic women was significantly lower than normotensive women (179 +/- 35 mg/dl
      vs 272 +/- 59 mg/dl, P < 0.001). Mean calcium to creatinine ratio was
      significantly lower in pre-eclamptic women (0.07 +/- 0.007 vs 0.16 +/- 0.006, P <
      0.001). The optimal cut off point for calcium to creatinine ratio was calculated
      to be 0.071 with a sensitivity of 77% and specificity of 78%. CONCLUSION: Urine
      calcium and calcium to creatinine ratio are lower in pre-eclamptic women and may
      be used as a screening test for the prediction of pre-eclampsia.

PMID- 22866875
TI  - Analysis of the causes and clinical characteristics of jejunoileal hemorrhage in
      China: a multicenter 10 year retrospective survey.
AB  - BACKGROUND: A retrospective study was performed to assess the causes, diagnostic
      methods for, and clinical features of, jejunoileal hemorrhage in Shandong
      province, China and to derive recommendations for management of this condition
      from these data. METHODS: We performed a retrospective systematic collection of
      data from between January 1999 and December 2008 in seven cities in Shandong
      province, China, identified 72 patients with jejunoileal hemorrhage and analyzed
      the relevant clinical data. RESULTS: Overall, tumors were the most common cause
      of jejunoileal hemorrhage (42 patients, 58.3%). The causes of this condition were
      significantly different (P < 0.05) in male and female patients. In male patients,
      the commonest factors were tumor (52.2%), enteritis (17.4%) and angiopathy
      (15.2%). However, in female patients, tumors accounted for a greater proportion
      of cases (18/26, 69.2%). In 38 cases (52.8%) the diagnosis was made by
      intraoperative enteroscopy or laparotomy, in 14 by capsule endoscopy and in the
      remainder by radiological methods. The most frequent presentation was melena
      (62.7%), followed by maroon stools (26.9%) and hematochezia (9.0%). Of the 72
      patients,laparotomy is the main treatment method. CONCLUSION: Tumor, enteritis
      and angiopathy and diverticular disease are the most common causes of jejunoileal
      hemorrhage in Shandong province, China. The main clinical manifestations are
      bloody stools, most commonly in the form of melena, with or without abdominal
      pain. We recommend that female patients over the age of 40 with jejunoileal
      hemorrhage accompanied by abdominal pain should undergo urgent further assessment
      because of the strong probability of jejunoileal tumor.

PMID- 22866876
TI  - Impact of a secondary prevention intervention among HIV-positive older women.
AB  - Despite the fact that older women represent a growing risk group for HIV, they
      have been rarely targeted by public health campaigns designed to prevent HIV/AIDS
      and are often excluded from many prevention studies. This unique cohort may be
      often overlooked due to beliefs that older women are not sexually active and do
      not engage in high risk sexual activity. Data suggest a need for increased
      attention to this unique cohort. Risk reduction interventions tailored to the
      special needs of people living with HIV/AIDS have begun to demonstrate promising
      results. In this manuscript, we report the 6 month outcomes for female
      participants in Project ROADMAP, a secondary prevention intervention designed to
      reduce high risk sexual behavior in older adults living with HIV/AIDS. Our
      results indicate that female participants in the intervention group were more
      likely to report a reduction in high risk sexual behavior than women in the
      control condition. Our findings also suggest that the intervention succeeded in
      increasing the HIV-related knowledge of the participants and decreasing their
      stigma vis-a-vis the HIV condition. The study findings suggest that Project
      ROADMAP is an effective secondary prevention intervention for sexually active
      older HIV positive women.

PMID- 22866877
TI  - Diastereotopos-differentiation in the Rh-catalyzed amination of benzylic
      methylene groups in the alpha-position to a stereogenic center.
AB  - The diastereoselectivity of the Rh-catalyzed C-H amination was examined with 18
      chiral open-chain substrates, which bear a benzylic methylene group in the alpha
      position to a stereogenic center (-CHMeX), and with four chiral cyclic tetralins,
      in which the stereogenic center was positioned at carbon atom C2. The C-H
      amination was performed using trichloroethoxysulfonyl-substituted amine
      (H(2)NTces) as the nitrogen source, a diacyloxyiodobenzene as the oxidant, and
      bis[rhodium(alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropionate)]
      [Rh(2)(esp)(2)] as the catalyst. For acyclic substrates a high syn
      diastereoselectivity (dr > 95/5) was found if the substituent X was Br,
      PO(OEt)(2), SO(2)Ph, or OOCCF(3) (eight examples). Moderate to good syn
      selectivities (dr = 80/20 to 91/9) were found for X = NO(2), OAc, COOMe, and CN
      (eight examples). Only two substrates gave a low diastereoselectivity. Kinetic
      isotope effect (KIE) experiments revealed that there is no secondary KIE when
      replacing -CHMeCOOMe by -CDMeCOOMe, but there is a significant primary KIE at the
      benzylic methylene position (4.8 +/- 0.7). Deuteration experiments provided
      evidence that the reaction proceeds stereospecifically with retention of
      configuration. A preferred conformation is proposed, which explains the outcome
      of the reaction. In this conformation the X substituent is antiperiplanar to the
      C-H bond, which is diastereoselectively attacked, and steric strain between the
      remaining substituents at the stereogenic and the prostereogenic center is
      minimized. DFT calculations support this model. They suggest, however, that the
      reaction is not concerted but occurs via hydrogen atom abstraction and subsequent
      radical rebound. Further support for an antiperiplanar attack relative to a given
      substituent X = Br, COOMe, or CN was obtained with the respective 2-substituted
      tetralins. Attack at C1 provides almost exclusively the trans-amination product.
      If the size of the X substituent increases [Br < CN < COOMe < PO(OEt)(2)], attack
      at the carbon atom C4 prevails, delivering the respective trans-amination
      products at this position.

PMID- 22866879
TI  - Music to heal by.

PMID- 22866878
TI  - Single siRNA nanocapsules for enhanced RNAi delivery.
AB  - Synthetic siRNA has been considered as a highly promising therapeutic agent for
      human diseases. However, clinical use of siRNA has been hampered by instability
      in the body and inability to deliver sufficient RNA interference compounds to the
      tissues or cells. To address this challenge, we present here a single siRNA
      nanocapsule delivery technology, which is achieved by encapsulating a single
      siRNA molecule within a degradable polymer nanocapsule with a diameter around 20
      nm and positive surface charge. As proof-of-concept, since CCR5 is considered a
      major silencing target of HIV therapy, CCR5-siRNA nanocapsules were delivered
      into 293T cells and successfully downregulated the CCR5 RNA fused with mCherry
      reporter RNA. In the absence of human serum, nanocapsules and lipofectamine
      silenced expression of CCR5-mCherry expression to 8% and 15%, respectively. Such
      nanocapsules maintain the integrity of siRNA inside even after incubation with
      ribonuclease and serum for 1 h; under the same conditions, siRNA is degraded in
      the native form or when formulated with lipofectamine. In the presence of serum,
      CCR5-siRNA nanocapsules knocked down CCR5-mCherry expression to less than 15%
      while siRNAs delivered through lipofectamine slightly knocked down the expression
      to 55%. In summary, this work provides a novel platform for siRNA delivery that
      can be developed for therapeutic purposes.

PMID- 22866884
TI  - Letting go of the bad: deficit in maintaining negative, but not positive, emotion
      in bipolar disorder.
AB  - Bipolar disorder is a disorder of emotion regulation. Less is known, however,
      about the specific processes that foster the maintenance of such prolonged and
      intense emotions-particularly positive-over time in this disorder. We
      investigated group-related differences in the ability to maintain positive and
      negative emotion representations over time using a previously validated emotion
      working memory task (Mikels et al., 2005, 2008) among individuals with bipolar I
      disorder (BD; n = 29) compared with both major depressive disorder (MDD; n = 29)
      and healthy control (n = 30) groups. Results revealed that the BD group exhibited
      a selective deficit in maintaining negative-but not positive-emotions compared to
      both the MDD and the control groups. The MDD and control groups did not differ
      significantly. These findings suggest that the heightened magnitude and duration
      of positive emotion observed in BD may, in part, be accounted for by difficulties
      maintaining negative emotions.

PMID- 22866886
TI  - Exploring the positive and negative implications of facial feedback.
AB  - The facial feedback effect (e.g., Strack et al., 1988) is explored in three
      experiments. It was found that when someone lowers their eyebrows, following
      instructions, their mood becomes more negative. If, however, they are instructed
      to raise their eyebrows they become more surprised by facts. Finally, if people
      are instructed to wrinkle their noses, then odors are evaluated as more
      unpleasant. While providing further diverse evidence for facial feedback, the
      experiments are also considered in the context of facial muscular paralysis
      induced as part of cosmetic treatments using botulinum toxin. The research
      presented here supports the previously suggested idea that such treatments could
      reduce depression, but other possible psychological impacts of such treatments
      are considered.

PMID- 22866885
TI  - Detecting and categorizing fleeting emotions in faces.
AB  - Expressions of emotion are often brief, providing only fleeting images from which
      to base important social judgments. We sought to characterize the sensitivity and
      mechanisms of emotion detection and expression categorization when exposure to
      faces is very brief, and to determine whether these processes dissociate.
      Observers viewed 2 backward-masked facial expressions in quick succession, 1
      neutral and the other emotional (happy, fearful, or angry), in a 2-interval
      forced-choice task. On each trial, observers attempted to detect the emotional
      expression (emotion detection) and to classify the expression (expression
      categorization). Above-chance emotion detection was possible with extremely brief
      exposures of 10 ms and was most accurate for happy expressions. We compared
      categorization among expressions using a d' analysis, and found that
      categorization was usually above chance for angry versus happy and fearful versus
      happy, but consistently poor for fearful versus angry expressions. Fearful versus
      angry categorization was poor even when only negative emotions (fearful, angry,
      or disgusted) were used, suggesting that this categorization is poor independent
      of decision context. Inverting faces impaired angry versus happy categorization,
      but not emotion detection, suggesting that information from facial features is
      used differently for emotion detection and expression categorizations. Emotion
      detection often occurred without expression categorization, and expression
      categorization sometimes occurred without emotion detection. These results are
      consistent with the notion that emotion detection and expression categorization
      involve separate mechanisms.

PMID- 22866887
TI  - Faces in the face of death: effects of exposure to life-threatening events and
      mortality salience on facial expression recognition in combat and noncombat
      military veterans.
AB  - Soldiers in war zones often experience life-threatening events that put their
      lives at stake. The present study examined how these exposures shape soldiers'
      social behavior, manifested by recognition of facial expressions. In addition, we
      investigated how explicit awareness of one's eventual death affects sensitivity
      to facial expressions. Veterans of elite military combat units were exposed to
      conditions of mortality or pain salience and later requested to label the
      emotions depicted in threatening and nonthreatening faces. Combat veterans were
      more accurate than noncombat veterans in identifying threatening expressions,
      both in mortality or pain salience induction (experiment 1) or under no induction
      at all (experiment 2). In addition, noncombat veterans primed with mortality
      salience identified fear expressions more accurately than those primed with pain
      salience. Finally, mortality salience improved accuracy for nonthreatening
      expressions for all veterans. The present results demonstrate that fear of death,
      resulting from exposure to concrete life-endangering perils or from thoughts on
      human's inevitable death, influences perception of facial expressions, which is
      critical for successful interpersonal communication.

PMID- 22866888
TI  - Aerosolized avian influenza virus by laboratory manipulations.
AB  - BACKGROUND: Avian H5N1 influenza viruses present a challenge in the laboratory
      environment, as they are difficult to collect from the air due to their small
      size and relatively low concentration. In an effort to generate effective methods
      of H5N1 air removal and ensure the safety of laboratory personnel, this study was
      designed to investigate the characteristics of aerosolized H5N1 produced by
      laboratory manipulations during research studies. RESULTS: Normal laboratory
      procedures used to process the influenza virus were carried out independently and
      the amount of virus polluting the on-site atmosphere was measured. In particular,
      zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation,
      and experimental zoogenetic infection were performed. In addition, common
      accidents associated with each process were simulated, including breaking glass
      containers, syringe injection of influenza virus solution, and rupturing of
      centrifuge tubes. A micro-cluster sampling ambient air pollution collection
      device was used to collect air samples. The collected viruses were tested for
      activity by measuring their ability to induce hemagglutination with chicken red
      blood cells and to propagate in chicken embryos after direct inoculation, the
      latter being detected by reverse-transcription PCR and HA test. The results
      showed that the air samples from the normal centrifugal group and the negative
      control group were negative, while all other groups were positive for H5N1.
      CONCLUSIONS: Our findings suggest that there are numerous sources of aerosols in
      laboratory operations involving H5N1. Thus, laboratory personnel should be aware
      of the exposure risk that accompanies routine procedures involved in H5N1
      processing and take proactive measures to prevent accidental infection and
      decrease the risk of virus aerosol leakage beyond the laboratory.

PMID- 22866889
TI  - Dose accuracy of new versus used Novopen 4 insulin pens.
AB  - OBJECTIVE: To our knowledge, no studies have been performed testing dose accuracy
      in both new and used patient insulin injection pens. We hypothesized that the
      dose accuracy of used (>1 year) insulin pens to be less accurate than that of new
      insulin pens and investigated whether possible differences influence the
      treatment. This study compared the dosing accuracy of 11 new and 11 used (>1
      year) Novopen((r)) 4 pens (Novo Nordisk, Bagsvaerd, Denmark). MATERIALS AND
      METHODS: Dosing accuracy differences between new and used pens were studied by
      weighing the volume of the dosage of 8 international units of insulin (IU) and 32
      IU of 11 pens. Each measurement was repeated 15 times. Whether the pens complied
      with the International Organization for Standardization (ISO) limits of 10% for 8
      IU and 5% for 32 IU was tested. The statistical analyses were performed using the
      Mann-Whitney rank sum test (within Sigmaplot version 12.0; Systat Software,
      Chicago, IL), and a P value of <0.05 was considered to be statistically
      significant. RESULTS: For the 8 IU dose, the mean delivered dose was 8.04 IU in
      new pens and 7.91 IU in used insulin pens. For the 32 IU dose, the mean delivered
      dose was 31.90 in new pens and 31.68 IU in used insulin pens. The difference in
      the median values between the two groups was statistically significant (P<0.001).
      Three individual doses in the 32 IU dose exceeded the ISO range in the lower
      range. The difference in mean variation coefficient between the two groups was
      also statistically significant (P<0.001). CONCLUSIONS: There was a significant
      difference between the accuracy of new versus used insulin pens. More studies
      with larger sample sizes are necessary to confirm our findings and further
      elucidate the relationship between age of insulin pens and dose accuracy.

PMID- 22866891
TI  - DRIFT: an analysis of outcome framing in intertemporal choice.
AB  - People prefer to receive good outcomes immediately rather than wait, and they
      must be compensated for waiting. But what influences their decision about how
      much compensation is required for a given wait? To give a partial answer to this
      question, we develop the DRIFT model, a heuristic description of how framing
      influences intertemporal choice. We describe 4 experiments showing the
      implications of this model. In the experiments, we vary how the difference
      between a smaller sooner outcome and a larger later outcome is framed-either as
      total interest earned, as an interest rate, or as total amount earned (the
      conventional frame in studies of intertemporal choice)-and whether the larger
      later outcome is described as resulting from the investment of the smaller sooner
      one. These alternate frames have several effects. First, the investment language
      increases patience. Second, the explicit provision of the (otherwise implicit)
      experimental interest rate sharply reduces the magnitude effect. Correspondingly,
      we find that interest frames increase patience when the rewards are small, but
      they decrease patience when they are large. Third, the interest-rate frame
      induces somewhat greater discounting for longer time periods and, thus, reverses
      the common finding of "hyperbolic" discounting. Thus, many of the "stylized
      facts" implied by studies involving choices between a smaller sooner and a larger
      later amount are eliminated or reverse under alternate outcome frames.

PMID- 22866890
TI  - Arctium lappa ameliorates endothelial dysfunction in rats fed with high
      fat/cholesterol diets.
AB  - BACKGROUND: Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is
      popularly used for treating hypertension, gout, hepatitis, and other inflammatory
      disorders. This study was performed to test the effect of ethanol extract of
      Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in
      rats fed a high fat/cholesterol diet (HFCD). METHOD: EAL-I (100 mg.kg-1/day), EAL
      II (200 mg.kg-1/day), and fluvastatin (3 mg.kg-1/day) groups initially received
      HFCD alone for 8 weeks, with EAL supplementation provided during the final 6
      weeks. RESULTS: Treatment with low or high doses of EAL markedly attenuated
      plasma levels of triglycerides and augmented plasma levels of high-density
      lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced
      impairments of acetylcholine (ACh)-induced relaxation of aortic rings.
      Furthermore, chronic treatment with EAL significantly lowered systolic blood
      pressure (SBP) and maintained smooth and flexible intimal endothelial layers in
      HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of
      intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)
      1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed
      increases in matrix metalloproteinase (MMP)-2 expression. These results suggested
      that EAL can inhibit HFCD-induced vascular inflammation in the rat model.
      CONCLUSION: The present study provides evidence that EAL ameliorates HFCD-induced
      vascular dysfunction through protection of vascular relaxation and suppression of
      vascular inflammation.

PMID- 22866893
TI  - Selective and effective binding of pillar[5,6]arenes toward secondary ammonium
      salts with a weakly coordinating counteranion.
AB  - The selective and effective binding of secondary ammoniums with a weakly
      coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF) counteranion
      by per-ethylated pillar[5,6]arenes is reported. The construction of a first
      pillararene-based self-sorting system consisting of two wheels and two axles is
      also described.

PMID- 22866892
TI  - Improving the care of people with traumatic brain injury through the Neurotrauma
      Evidence Translation (NET) program: protocol for a program of research.
AB  - The Neurotrauma Evidence Translation (NET) program was funded in 2009 to increase
      the uptake of research evidence in the clinical care of patients who have
      sustained traumatic brain injury. This paper reports the rationale and plan for
      this five-year knowledge translation research program. The overarching aims of
      the program are threefold: to improve outcomes for people with traumatic brain
      injury; to create a network of neurotrauma clinicians and researchers with
      expertise in knowledge translation and evidence-based practice; and to contribute
      knowledge to the field of knowledge translation research. The program comprises a
      series of interlinked projects spanning varying clinical environments and
      disciplines relevant to neurotrauma, anchored within four themes representing
      core knowledge translation activities: reviewing research evidence; understanding
      practice; developing and testing interventions for practice change; and building
      capacity for knowledge translation in neurotrauma. The program uses a range of
      different methods and study designs, including: an evidence fellowship program;
      conduct of and training in systematic reviews; mixed method study designs to
      describe and understand factors that influence current practices (e.g., semi
      structured interviews and surveys); theory-based methods to develop targeted
      interventions aiming to change practice; a cluster randomised trial to test the
      effectiveness of a targeted theory-informed intervention; stakeholder involvement
      activities; and knowledge translation events such as consensus conferences.

PMID- 22866894
TI  - Effects on platelet function of an EP3 receptor antagonist used alone and in
      combination with a P2Y12 antagonist both in-vitro and ex-vivo in human
      volunteers.
AB  - EP3 receptor antagonists may provide a new approach to the treatment of
      atherothrombotic disease by blocking the ability of prostaglandin E2 (PGE2) to
      promote platelet function acting via EP3 receptors. DG-041 is an EP3 antagonist
      in the early stage of clinical development. Here, we quantitated effects on
      platelet function of DG-041 in-vitro and ex-vivo after administration to man when
      given alone and concomitantly with clopidogrel or clopidogrel and aspirin. With
      its unique mechanism of action, it was anticipated that DG-041 would potentiate
      inhibition of platelet function when given in combination with clopidogrel
      without materially increasing bleeding time. Initially, in-vitro studies were
      performed to determine inhibitory effects of DG-041 (3 uM) used alone or in
      combination with the P2Y12 antagonist cangrelor (1 uM), both without and with
      aspirin (100 uM). Platelet aggregation and P-selectin expression were measured in
      whole blood (n = 10) following stimulation with the thromboxane A2 (TXA2) mimetic
      U46619 (0.3 or 1 uM) in combination with either the EP3 agonist sulprostone (0.1
      uM), or PGE2 (1 uM). DG-041 alone partially inhibited platelet function in-vitro,
      as did cangrelor. Addition of both DG-041 and cangrelor in combination provided
      significantly greater inhibition. An ex-vivo study was then performed using the
      same experimental approaches. This clinical study was a prospective, randomised,
      blinded (for DG-041/matching placebo), blocked, crossover study designed to
      compare the effects of DG-041, clopidogrel, or the combination of DG-041 with
      either clopidogrel or clopidogrel and aspirin. Healthy volunteers (n = 42) were
      randomly assigned to receive no background treatment, clopidogrel (300 mg loading
      dose plus 75 mg daily) or clopidogrel and aspirin (75 mg daily) for 10 days
      alongside DG-041 (200 mg twice daily) or placebo for 5 days, crossed over to
      placebo or DG-041 for the next 5 days. Platelet effects and bleeding time were
      measured at baseline, days 5 and 10. DG-041 partially inhibited platelet function
      ex-vivo, as did clopidogrel, while administration of both DG-041 and clopidogrel
      provided significantly greater inhibition. Administration of DG-041 alone did not
      increase bleeding time, and did not significantly affect the increased bleeding
      time seen with clopidogrel or clopidogrel with aspirin. Using these experimental
      approaches, the antiplatelet effects of DG-041 and a P2Y12 antagonist used alone
      and in combination can be determined both in-vitro and ex-vivo. Results show
      inhibitory effects of DG-041 on platelet function acting via EP3 receptor
      blockade, confirmed to be additional to those brought about by P2Y12 blockade. In
      both in-vitro and ex-vivo studies, aspirin neither promoted nor negated the
      effects of the other drugs. 

PMID- 22866895
TI  - Linking land cover and species distribution models to project potential ranges of
      malaria vectors: an example using Anopheles arabiensis in Sudan and Upper Egypt.
AB  - BACKGROUND: Anopheles arabiensis is a particularly opportunistic feeder and
      efficient vector of Plasmodium falciparum in Africa and may invade areas outside
      its normal range, including areas separated by expanses of barren desert. The
      purpose of this paper is to demonstrate how spatial models can project future
      irrigated cropland and potential, new suitable habitat for vectors such as An.
      arabiensis. METHODS: Two different but complementary spatial models were linked
      to demonstrate their synergy for assessing re-invasion potential of An.
      arabiensis into Upper Egypt as a function of irrigated cropland expansion by
      2050. The first model (The Land Change Modeler) was used to simulate changes in
      irrigated cropland using a Markov Chain approach, while the second model (MaxEnt)
      uses species occurrence points, land cover and other environmental layers to
      project probability of species presence. Two basic change scenarios were
      analysed, one involving a more conservative business-as-usual (BAU) assumption
      and second with a high probability of desert-to-cropland transition (Green Nile)
      to assess a broad range of potential outcomes by 2050. RESULTS: The results
      reveal a difference of 82,000 sq km in potential An. arabiensis range between the
      BAU and Green Nile scenarios. The BAU scenario revealed a highly fragmented set
      of small, potential habitat patches separated by relatively large distances
      (maximum distance = 64.02 km, mean = 12.72 km, SD = 9.92), while the Green Nile
      scenario produced a landscape characterized by large patches separated by
      relatively shorter gaps (maximum distance = 49.38, km, mean = 4.51 km, SD = 7.89)
      that may be bridged by the vector. CONCLUSIONS: This study provides a first
      demonstration of how land change and species distribution models may be linked to
      project potential changes in vector habitat distribution and invasion potential.
      While gaps between potential habitat patches remained large in the Green Nile
      scenario, the models reveal large areas of future habitat connectivity that may
      facilitate the re-invasion of An. arabiensis from Sudan into Upper Egypt. The
      methods used are broadly applicable to other land cover changes as they influence
      vector distribution, particularly those related to tropical deforestation and
      urbanization processes.

PMID- 22866896
TI  - Addition of low dose hCG to rFSh benefits older women during ovarian stimulation
      for IVF.
AB  - BACKGROUND: To compare the outcome of IVF cycles in women receiving controlled
      ovarian stimulation with recFSH or recFSH plus low dose hCG. METHODS: A
      retrospective case control study, performed at a private practice affiliated with
      an academic institute. Patients were infertile women who were treated with
      IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using
      either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99].
      Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized
      eggs, and serum levels of estradiol. Secondary outcomes were endometrial
      thickness, cycle cancellations and pregnancy rates. RESULTS: A significant
      increase in number of mature and fertilized eggs was observed in women over 40
      years of age using low dose hCG in addition to recFSH. The estradiol level was
      significantly higher on the day of hCG administration and the serum level of FSH
      on cycle day 7 and on the day of hCG administration were lower. CONCLUSION:
      Addition of low dose hCG to recFSH compared with recFSH alone significantly
      modified cycle characteristics in patients >/= 40 years and could be of potential
      benefit for IVF cycles in older infertile women.

PMID- 22866898
TI  - One-step-process composite colloidal monolayers and further processing aiming at
      porous membranes.
AB  - Composite materials consisting of a monolayer of polystyrene spheres (diameters
      of 430 and 520 nm) and porous silica, filling in the interstices, have been
      fabricated and characterized. The proposed growth method introduces some
      novelties as far as the fabrication of this kind of monolayers is concerned, as
      it probes the compatibility of coassembly (in which a silica precursor,
      tetraethyl orthosilicate (TEOS), is added to the base colloid) with confined
      growth in a wedge-shaped cell, while profiting from the advantages of both
      techniques. Using this method, it is possible to fabricate the composite
      monolayer in a single growth step. A systematic study of the influence of TEOS
      concentration in the initial colloid was performed in order to improve the
      quality of the two-dimensional crystals produced. Thus, it was demonstrated that
      the two methods are compatible. Furthermore, the composites were then subjected
      to thermal treatment so that the polymer is removed to reveal the inverse
      structure. After the calcination the membranes still present very good quality
      and so the proposed approach is effective for the fabrication of porous
      membranes. A comparison of reflectance spectra, between composite monolayers
      fabricated using this method and composites achieved by infiltrating polystyrene
      bare opals with silica chemical vapor deposition, is also established. The
      procedure presented is expected to establish the route for an easier and quicker
      fabrication of inverse monolayers of high refractive index materials with
      applications in light control.

PMID- 22866897
TI  - PSMA-targeted theranostic nanoplex for prostate cancer therapy.
AB  - Theranostic imaging, where diagnosis is combined with therapy, is particularly
      suitable for a disease that is as complex as cancer, especially now that genomic
      and proteomic profiling can provide an extensive "fingerprint" of each tumor.
      With such information, theranostic agents can be designed to personalize
      treatment and minimize damage to normal tissue. Here we have developed a nanoplex
      platform for theranostic imaging of prostate cancer (PCa). In these proof-of
      principle studies, a therapeutic nanoplex containing multimodal imaging reporters
      was targeted to prostate-specific membrane antigen (PSMA), which is expressed on
      the cell surface of castrate-resistant PCa. The nanoplex was designed to deliver
      small interfering RNA (siRNA) along with a prodrug enzyme to PSMA-expressing
      tumors. Each component of the nanoplex was carefully selected to evaluate its
      diagnostic aspect of PSMA imaging and its therapeutic aspects of siRNA-mediated
      down-regulation of a target gene and the conversion of a prodrug to cytotoxic
      drug, using noninvasive multimodality imaging. Studies performed using two
      variants of human PC3-PCa cells and tumors, one with high PSMA expression level
      and another with negligible expression levels, demonstrated PSMA-specific uptake.
      In addition, down-regulation of the selected siRNA target, choline kinase (Chk),
      and the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5
      fluorouracil (5-FU) were also demonstrated with noninvasive imaging. The nanoplex
      was well-tolerated and did not induce liver or kidney toxicity or a significant
      immune response. The nanoplex platform described can be easily modified and
      applied to different cancers, receptors, and pathways to achieve theranostic
      imaging, as a single agent or in combination with other treatment modalities.

PMID- 22866899
TI  - Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on
      HIFs and angiogenesis in RA.
AB  - INTRODUCTION: Hypoxia and T-helper cell 1 (Th1) cytokine-driven inflammation are
      key features of rheumatoid arthritis (RA) and contribute to disease pathogenesis
      by promoting angiogenesis. The objective of our study was to characterise the
      angiogenic gene signature of RA fibroblast-like synoviocytes (FLS) in response to
      hypoxia, as well as Th1 and T-helper cell 2 (Th2) cytokines, and in particular to
      dissect out effects of combined hypoxia and cytokines on hypoxia inducible
      transcription factors (HIFs) and angiogenesis. METHODS: Human angiogenesis PCR
      arrays were used to screen cDNA from RA FLS exposed to hypoxia (1% oxygen) or
      dimethyloxalylglycine, which stabilises HIFs. The involvement of HIF isoforms in
      generating the angiogenic signature of RA FLS stimulated with hypoxia and/or
      cytokines was investigated using a DNA-binding assay and RNA interference. The
      angiogenic potential of conditioned media from hypoxia-treated and/or cytokine
      treated RA FLS was measured using an in vitro endothelial-based assay. RESULTS:
      Expression of 12 angiogenic genes was significantly altered in RA FLS exposed to
      hypoxia, and seven of these were changed by dimethyloxalylglycine, including
      ephrin A3 (EFNA3), vascular endothelial growth factor (VEGF), adipokines
      angiopoietin-like (ANGPTL)-4 and leptin. These four proangiogenic genes were
      dependent on HIF-1 in hypoxia to various degrees: EFNA3 >ANGPTL-4 >VEGF >leptin.
      The Th1 cytokines TNFalpha and IL-1beta induced HIF-1 but not HIF-2 transcription
      as well as activity, and this effect was additive with hypoxia. In contrast, Th2
      cytokines had no effect on HIFs. IL-1beta synergised with hypoxia to upregulate
      EFNA3 and VEGF in a HIF-1-dependent fashion but, despite strongly inducing HIF-1,
      TNFalpha suppressed adipokine expression and had minimal effect on EFNA3.
      Supernatants from RA FLS subjected to hypoxia and TNFalpha induced fewer
      endothelial tubules than those from FLS subjected to TNFalpha or hypoxia alone,
      despite high VEGF protein levels. The Th2 cytokine IL-4 strongly induced ANGPTL-4
      and angiogenesis by normoxic FLS and synergised with hypoxia to induce further
      proangiogenic activity. CONCLUSION: The present work demonstrates that Th1
      cytokines in combination with hypoxia are not sufficient to induce angiogenic
      activity by RA FLS despite HIF-1 activation and VEGF production. In contrast, Th2
      cytokines induce angiogenic activity in normoxia and hypoxia, despite their
      inability to activate HIFs, highlighting the complex relationships between
      hypoxia, angiogenesis and inflammation in RA.

PMID- 22866900
TI  - Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and
      behaviour in younger patients with Crohn's disease.
AB  - BACKGROUND: Glycoprotein 2 (GP2) was discovered as the major autoantigen of
      Crohn's disease (CD)-specific pancreatic autoantibodies (PAB). We investigated
      anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and
      assessed their association with distinct disease phenotypes. METHODS: Anti-GP2
      and anti-Saccharomyces cerevisiae (ASCA) IgA and IgG were detected by ELISA
      employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by
      indirect immunofluorescence (IIF) in 271 sera, 169 with CD and 102 with
      ulcerative colitis (UC). As healthy controls 160 adult blood donors and 65
      children were included. RESULTS: Anti-GP2 IgG and/or IgA were more prevalent in
      CD (51/169, 30.2%) than in UC (9/102, 8.9%) patients and in controls (9/225, 4%)
      (p < 0.001 respectively). ASCA IgG and/or IgA were present in 60/169 (35.5%) in
      CD and in 7/102 (6.9%) in UC patients (p < 0.001). CD patients with ileocolonic
      location (L3) showed a significantly higher prevalence of anti-GP2 and ASCA IgA
      and/or IgG (40/113 and 48/113, respectively; p < 0.05 for both comparisons),
      whereas CD patients with colonic location (L2) revealed a significantly
      diminished prevalence for these autoantibody specificities (2/32 and 5/32,
      respectively, p < 0.05 for both). Anti-GP2 IgG were significantly more prevalent
      in CD patients with stricturing behaviour (B2) and perianal disease (7/11, p <
      0.02) and less prevalent in those with penetrating behaviour (B3) and perianal
      disease (4/31, p < 0.05). The occurrence of anti-GP2 IgA and/or IgG was
      significantly more prevalent in CD patients with age at diagnosis of <=16 years
      (16/31, p < 0.009). Prevalence of one or more anti-GP2 or ASCA IgA and/or IgG was
      significantly higher in L3, B2, and A1 and lower in L2 (68/113, 27/41, 23/31,
      6/32; p < 0.04, respectively). CONCLUSIONS: Anti-GP2 IgG and IgA, constituting
      novel CD specific autoantibodies, appear to be associated with distinct disease
      phenotypes identifying patients at a younger age, with ileocolonic location, and
      stricturing behaviour with perianal disease.

PMID- 22866901
TI  - Fine mapping of copy number variations on two cattle genome assemblies using high
      density SNP array.
AB  - BACKGROUND: Btau_4.0 and UMD3.1 are two distinct cattle reference genome
      assemblies. In our previous study using the low density BovineSNP50 array, we
      reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of
      21 cattle breeds, yielding 682 CNV regions with a total length of 139.8
      megabases. RESULTS: In this study using the high density BovineHD SNP array, we
      performed high resolution CNV analyses on both Btau_4.0 and UMD3.1 with 674
      animals of 27 cattle breeds. We first compared CNV results derived from these two
      different SNP array platforms on Btau_4.0. With two thirds of the animals shared
      between studies, on Btau_4.0 we identified 3,346 candidate CNV regions
      representing 142.7 megabases (~4.70%) of the genome. With a similar total length
      but 5 times more event counts, the average CNVR length of current Btau_4.0
      dataset is significantly shorter than the previous one (42.7 kb vs. 205 kb).
      Although subsets of these two results overlapped, 64% (91.6 megabases) of current
      dataset was not present in the previous study. We also performed similar analyses
      on UMD3.1 using these BovineHD SNP array results. Approximately 50% more and 20%
      longer CNVs were called on UMD3.1 as compared to those on Btau_4.0. However, a
      comparable result of CNVRs (3,438 regions with a total length 146.9 megabases)
      was obtained. We suspect that these results are due to the UMD3.1 assembly's
      efforts of placing unplaced contigs and removing unmerged alleles. Selected CNVs
      were further experimentally validated, achieving a 73% PCR validation rate, which
      is considerably higher than the previous validation rate. About 20-45% of CNV
      regions overlapped with cattle RefSeq genes and Ensembl genes. Panther and IPA
      analyses indicated that these genes provide a wide spectrum of biological
      processes involving immune system, lipid metabolism, cell, organism and system
      development. CONCLUSION: We present a comprehensive result of cattle CNVs at a
      higher resolution and sensitivity. We identified over 3,000 candidate CNV regions
      on both Btau_4.0 and UMD3.1, further compared current datasets with previous
      results, and examined the impacts of genome assemblies on CNV calling.

PMID- 22866902
TI  - Quantification of hormone-humic acid interactions in nanofiltration.
AB  - The influence of solute-solute interactions on hormone retention during
      nanofiltration (NF) was quantified and mechanisms underlying retention
      identified. A new approach to predict both the mass of hormone sorbed to organic
      matter and the retention of hormone influenced by solute-solute interactions was
      applied. Laboratory-scale experiments were carried out in a cross-flow filtration
      system examining organic matter concentration, solution pH, and hormone type.
      Solute-solute interactions between HA and estrone improved estrone retention
      while decreasing estrone adsorption to membranes. HA concentration determined the
      amount of estrone bound to HA and hence affected estrone retention based on the
      mechanism of size exclusion. The solution pH influenced both solute-solute as
      well as solute-membrane interactions. Solute-solute interactions were most
      important below the pK(a) of estrone, whereas charge repulsion between estrone
      and negative functional groups of the membrane dominated estrone retention above
      the pK(a). Of the four hormones studied, progesterone had the greatest affinity
      for both HA and NF membrane, which was attributed to hydrogen bonding ability.
      Using partition coefficients K(OM) from solid-phase microextraction (SPME)
      resulted in very good agreement between predicted and experimental retention.

PMID- 22866904
TI  - Length control and block-type architectures in worm-like micelles with
      polyethylene cores.
AB  - We present evidence for "living"-like behavior in the crystallization-driven self
      assembly of triblock copolymers with crystallizable polyethylene middle blocks
      into worm-like crystalline-core micelles (CCMs). A new method of seed production
      is introduced utilizing the selective self-assembly of the triblock copolymers
      into spherical CCMs in appropriate solvents. Seeded growth of triblock copolymer
      unimers from these spherical CCMs results in worm-like CCMs with narrow length
      distributions and mean lengths that depend linearly on the applied unimer-to-seed
      ratio. Depending on the applied triblock copolymer, polystyrene-block
      polyethylene-block-polystyrene (SES) or polystyrene-block-polyethylene-block
      poly(methyl methacrylate) (SEM), well-defined worm-like CCMs with a homogeneous
      or patch-like corona, respectively, can be produced. In a subsequent step, these
      worm-like CCMs can be used as seeds for the epitaxial growth of a different
      polyethylene containing triblock copolymer. In this manner, ABA-type triblock co
      micelles containing blocks with a homogeneous polystyrene corona and those with a
      patch-like polystyrene/poly(methyl methacrylate) corona were prepared. While the
      epitaxial growth of SEM unimers from worm-like SES CCMs with a homogeneous corona
      yields triblock co-micelles almost quantitatively, the addition of SES unimers to
      patchy SEM wCCMs results in a mixture of ABA- and AB-type block co-micelles
      together with residual patchy wCCMs. Following reports on self-assembled block
      type architectures from polymers containing core-forming polyferrocenylsilane
      blocks, these structures represent the first extension of the concept to block co
      micelles from purely organic block copolymers.

PMID- 22866903
TI  - Theoretical models of parental HIV disclosure: a critical review.
AB  - This study critically examined three major theoretical models related to parental
      HIV disclosure (i.e., the Four-Phase Model [FPM], the Disclosure Decision Making
      Model [DDMM], and the Disclosure Process Model [DPM]), and the existing studies
      that could provide empirical support to these models or their components. For
      each model, we briefly reviewed its theoretical background, described its
      components and/or mechanisms, and discussed its strengths and limitations. The
      existing empirical studies supported most theoretical components in these models.
      However, hypotheses related to the mechanisms proposed in the models have not yet
      tested due to a lack of empirical evidence. This study also synthesized
      alternative theoretical perspectives and new issues in disclosure research and
      clinical practice that may challenge the existing models. The current study
      underscores the importance of including components related to social and cultural
      contexts in theoretical frameworks, and calls for more adequately designed
      empirical studies in order to test and refine existing theories and to develop
      new ones.

PMID- 22866905
TI  - Oxidative ipso-rearrangement performed by a hypervalent iodine reagent and its
      application.
AB  - An oxidative ipso-rearrangement mediated by a hypervalent iodine reagent that
      enables rapid generation of a functionalized dienone system containing a
      quaternary carbon center connected to several sp(2) centers has been developed.
      The process occurs through transfer of an aryl group from a silyl segment present
      on the lateral chain. As an illustration of the potential of this transformation,
      a total synthesis of sceletenone, a small alkaloid, is described.

PMID- 22866906
TI  - Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice.
AB  - BACKGROUND: In the present study, we examined the antioxidant effect of water
      soluble derivative of propolis (WSDP) and ethanolic (EEP) extract of propolis on
      renal and liver function in alloxan-induced diabetic mice. In addition, we
      examined whether different extract of propolis could prevent diabetic nephropathy
      and liver toxicity by inhibiting lipid peroxidation in vivo. METHODS: Diabetes
      was induced in Swiss albino mice with a single intravenous injection of alloxan
      (75 mg kg-1). Two days after alloxan injection, propolis preparations (50 mg kg-1
      per day) were given intraperitoneally for 7 days in diabetic mice. Survival
      analysis and body weights as well as hematological and biochemical parameters
      were measured. The renal and liver oxidative stress marker malonaldehyde levels
      and histopathological changes were monitored in the liver and kidney of treated
      and control mice. RESULTS: Administration of propolis to diabetic mice resulted
      in a significant increase of body weight, haematological and immunological
      parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected
      mice showed a marked increase in oxidative stress in liver and kidney homogenate,
      as determined by lipid peroxidation. Histopathological observation of the liver
      sections of alloxan-induced diabetic mice showed several lesions including
      cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations,
      but with individual variability.Treatment of diabetic mice with propolis extracts
      results in decreased number of vacuolized cells and degree of vacuolization;
      propolis treatment improve the impairment of fatty acid metabolism in diabetes.
      Renal histology showed corpuscular, tubular and interstitial changes in alloxan
      induced diabetic mice. Test components did not improve renal histopathology in
      diabetic mice. CONCLUSIONS: Propolis preparations are able to attenuate diabetic
      hepatorenal damage, probably through its anti-oxidative action and its
      detoxification proccess as well as the potential to minimize the deleterious
      effects of free radicals on tissue. The protective role of propolis against the
      ROS induced damages in diabetic mice gives a hope that they may have similar
      protective action in humans.

PMID- 22866907
TI  - Correlation of serum C-reactive protein, white blood count and neutrophil
      percentage with histopathology findings in acute appendicitis.
AB  - BACKGROUND: Acute appendicitis is one of the most common surgical emergencies.
      Accurate diagnosis of acute appendicitis is based on careful history, physical
      examination, laboratory and imaging investigation. The aim of the study is to
      analyze the role of C-reactive protein (CRP), white blood count (WBC) and
      Neutrophil percentage (NP) in improving the accuracy of diagnosis of acute
      appendicitis and to compare it with the intraoperative assessment and
      histopathology findings. MATERIALS AND METHODS: This investigation was a
      prospective double blinded clinical study. The study was done on 173 patients
      surgically treated for acute appendicitis. The WBC, NP, and measurement of CRP
      were randomly collected pre-operatively from all involved patients. Macroscopic
      assessment was made from the operation. Appendectomy and a histopathology
      examination were performed on all patients. Gross description was compared with
      histopathology results and then correlated with CRP, WBC, and NP. RESULTS: The
      observational accuracy was 87,3%, as compared to histopathological accuracy which
      was 85.5% with a total of 173 patients that were operated on. The histopathology
      showed 25 (14.5%) patients had normal appendices, and 148 (85.5%) patients had
      acutely inflamed, gangrenous, or perforated appendicitis. 52% were male and 48%
      were female, with the age ranging from 5 to 59 with a median of 19.7. The
      gangrenous type was the most frequent (52.6%). The WBC was altered in 77.5% of
      the cases, NP in 72.3%, and C-reactive protein in 76.9% cases. In those with
      positive appendicitis, the CRP and WBC values were elevated in 126 patients
      (72.8%), whereas NP was higher than 75% in 117 patients (67.6%). Out of 106
      patients with triple positive tests, 101 (95.2%) had appendicitis. The
      sensitivity, specificity, and positive predictive values of the 3 tests in
      combination were 95.3%, 72.2%, and 95.3%, respectively. CONCLUSION: The raised
      value of the CRP was directly related to the severity of inflammation (p-value
      <0.05). CRP monitoring enhances the diagnostic accuracy of acute appendicitis.
      The diagnostic accuracy of CRP is not significantly greater than WBC and NP. A
      combination of these three tests significantly increases the accuracy. We found
      that elevated serum CRP levels support the surgeon's clinical diagnosis.

PMID- 22866908
TI  - Systemic thromboembolic adverse events in patients treated with intravitreal anti
      VEGF drugs for neovascular age-related macular degeneration.
AB  - INTRODUCTION: The consistent association between choroid neovascularization (CNV)
      and increased VEGF-A expression provides a strong reason for exploring the
      therapeutic potential of anti-VEGF agents in the treatment of neovascular age
      related macular degeneration (AMD). The authors report the systemic side effects
      secondary to intravitreal administration of these compounds, that is, the main
      cardiovascular effects, as well as the less frequent cerebrovascular accidents,
      myocardial infarction, transient ischemic attacks, deep vein thrombosis,
      pulmonary embolism and thromboflebitis. AREAS COVERED: The authors reviewed major
      Clinical Trials and publications concerning systemic adverse events of anti-VEGF
      drugs in order to identify the main thromboembolic events related to the use of
      these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability
      are also discussed. EXPERT OPINION: Three compounds (pegaptanib, ranibizumab and
      aflibercept) have been approved for the treatment of AMD; a fourth agent,
      bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to
      fully eradicate the CNV, so that recurrences are common when the intravitreal
      injections are suspended. Although no evident rise in anti-VEGF-induced
      thromboembolic side effects was reported, more data are required to evaluate
      hemodynamic and pharmacokinetics of these compounds. Since only few studies have
      focused on these aspects, further researches are mandatory to determine
      distribution, effects and duration of these substances.

PMID- 22866910
TI  - Pile sorting innovations: exploring gender norms, power and equity in sub-Saharan
      Africa.
AB  - Understanding gender norms, power and equity is important for developing
      successful sexual and reproductive health interventions. However, little
      attention has been given to how to capture the gender ideals and imbalances that
      inform these relationships in low resource settings. Pile sorting exercises were
      conducted in four gender-segregated focus groups in Ethiopia and Kenya. Each
      group received cards illustrated with a man, woman and man and woman together and
      cards labelled with duties and decisions. Participants discussed and decided
      together whether men, women or both performed each duty and decision and assigned
      the cards accordingly. Participants then reflected on and physically manipulated
      the piles to challenge gender norms, investigate role flexibility and identify
      agents of social change. Data collected included photographs of the pile sorts
      and recordings of the discussions. Conducting pile sorting within focus group
      discussions enabled comparative analyses of gender norms, while enriching data by
      focusing discussions and encouraging consensus building. Innovative applications
      facilitated participants' abilities to engage abstract concepts, reflecting on
      issues of gender norms, power and equity.

PMID- 22866909
TI  - Trial protocol OPPTIMUM-- does progesterone prophylaxis for the prevention of
      preterm labour improve outcome?
AB  - BACKGROUND: Preterm birth is a global problem, with a prevalence of 8 to 12%
      depending on location. Several large trials and systematic reviews have shown
      progestogens to be effective in preventing or delaying preterm birth in selected
      high risk women with a singleton pregnancy (including those with a short cervix
      or previous preterm birth). Although an improvement in short term neonatal
      outcomes has been shown in some trials these have not consistently been confirmed
      in meta-analyses. Additionally data on longer term outcomes is limited to a
      single trial where no difference in outcomes was demonstrated at four years of
      age of the child, despite those in the "progesterone" group having a lower
      incidence of preterm birth. METHODS/DESIGN: The OPPTIMUM study is a double blind
      randomized placebo controlled trial to determine whether progesterone prophylaxis
      to prevent preterm birth has long term neonatal or infant benefit. Specifically
      it will study whether, in women with singleton pregnancy and at high risk of
      preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 -
      34 weeks gestation, compared to placebo, improves obstetric outcome by
      lengthening pregnancy thus reducing the incidence of preterm delivery (before 34
      weeks), improves neonatal outcome by reducing a composite of death and major
      morbidity, and leads to improved childhood cognitive and neurosensory outcomes at
      two years of age. Recruitment began in 2009 and is scheduled to close in Spring
      2013. As of May 2012, over 800 women had been randomized in 60 sites. DISCUSSION:
      OPPTIMUM will provide further evidence on the effectiveness of vaginal
      progesterone for prevention of preterm birth and improvement of neonatal outcomes
      in selected groups of women with singleton pregnancy at high risk of preterm
      birth. Additionally it will determine whether any reduction in the incidence of
      preterm birth is accompanied by improved childhood outcome. TRIAL REGISTRATION:
      ISRCTN14568373.

PMID- 22866911
TI  - The major G-quadruplex formed in the human platelet-derived growth factor
      receptor beta promoter adopts a novel broken-strand structure in K+ solution.
AB  - Overexpression of platelet-derived growth factor receptor beta (PDGFR-beta) has
      been associated with cancers and vascular and fibrotic disorders. PDGFR-beta has
      become an attractive target for the treatment of cancers and fibrotic disorders.
      DNA G-quadruplexes formed in the GC-rich nuclease hypersensitivity element of the
      human PDGFR-beta gene promoter have been found to inhibit PDGFR-beta
      transcriptional activity. Here we determined the major G-quadruplex formed in the
      PDGFR-beta promoter. Instead of using four continuous runs with three or more
      guanines, this G-quadruplex adopts a novel folding with a broken G-strand to form
      a primarily parallel-stranded intramolecular structure with three 1 nucleotide
      (nt) double-chain-reversal loops and one additional lateral loop. The novel
      folding of the PDGFR-beta promoter G-quadruplex emphasizes the robustness of
      parallel-stranded structural motifs with a 1 nt loop. Considering recent progress
      on G-quadruplexes formed in gene-promoter sequences, we suggest the 1 nt looped
      G(i)NG(j) motif may have been evolutionarily selected to serve as a stable
      foundation upon which the promoter G-quadruplexes can build. The novel folding of
      the PDGFR-beta promoter G-quadruplex may be attractive for small-molecule drugs
      that specifically target this secondary structure and modulate PDGFR-beta gene
      expression.

PMID- 22866912
TI  - Shape of snack foods does not predict snack intake in a sample of preschoolers: a
      cross-over study.
AB  - BACKGROUND: In the past decade, the proportion snacking has increased. Snack
      foods consumed are predominantly not nutritious foods. One potential venue to
      increase children's diet quality is to offer healthy snack foods and we explored
      if shaped snack foods would lead to increased consumption. METHODS: We
      investigated the consumption of high-fiber snacks (banana bread, pancakes, and
      sandwiches) served either in normal (round, square) or shaped (heart, hands,
      animals) form to preschoolers 2-5 years old attending a local child care center
      (n = 21). The 9 weeks long, prospective, cross-over intervention study was
      designed to expose each child repeatedly to each snack in each shape (4 times per
      snack). Snacks were served as morning or afternoon snack and caretakers' reports
      were used to account for the child's consumption of a meal preceding the study
      snack (breakfast or lunch). RESULTS: There was no significant difference in snack
      consumption between the shaped and normal snacks. However, the mean energy intake
      from snacks was significantly greater for Caucasian children compared with Asian
      children. Further, Asian children consumed much less banana bread than the other
      two snacks. Overall, children who had not eaten breakfast or lunch prior to the
      morning or afternoon snack ate significantly more calories from the snacks (84.1
      kcal, p-value < 0.0001). CONCLUSION: Findings of this study confirm previous
      research that the shape of the foods does not affect snack consumption in
      children. However, we also report two unexpected findings: a) the strong
      interaction between ethnicity and snack consumption and b) that Asian children
      consumed much less banana bread than Caucasian children. The role of children's
      ethnic background profoundly affects snack preference and must be considered in
      the study of children's eating behaviors and in interventions to promote healthy
      eating habits.

PMID- 22866914
TI  - Cancer support services--are they appropriate and accessible for Indigenous
      cancer patients in Queensland, Australia?
AB  - INTRODUCTION: In Queensland, Australia, the incidence of cancer (all cancers
      combined) is 21% lower for Indigenous people compared with non-Indigenous people
      but mortality is 36% higher. Support services play an important role in helping
      cancer patients through their cancer journey. Indigenous cancer patients are
      likely to face greater unmet supportive care needs and more barriers to accessing
      cancer care and support. Other barriers include the higher proportion of
      Indigenous people who live remotely and in regional areas, a known difficulty for
      access to health services. This study describes the availability of cancer
      support services in Queensland for Indigenous patients and relevant location.
      METHODS: Using a set criteria 121 services were selected from a pre-existing
      database (n = 344) of cancer services. These services were invited to complete an
      online questionnaire. ArcGIS (http://www.esri.com/software/arcgis/index.html) was
      used to map the services' location (using postcode) against Indigenous population
      by local government area. Services were classified as an 'Indigenous' or
      'Indigenous friendly' service using set criteria. RESULTS: Eighty-three services
      (73.6%) completed the questionnaire. Mapping revealed services are located where
      there are relatively low percentages of Indigenous people compared with the whole
      population. No 'Indigenous-specific' services were identified; however, 11
      services (13%) were classed 'Indigenous-friendly'. The primary support offered by
      these services was 'information'. Fewer referrals were received from Indigenous
      liaison officers compared with other health professionals. Only 8.6% of services
      reported frequently having contact with an Indigenous organisation; however,
      44.6% of services reported that their staff participated in cultural training.
      Services also identified barriers to access which may exist for Indigenous
      clientele, including no Indigenous staff and the costs involved in accessing the
      service, but were unable to address these issues due to restricted staff and
      funding capacity. CONCLUSION: Further research into the best models for providing
      culturally appropriate cancer support services to Indigenous people is essential
      to ensure Indigenous patients are well supported throughout their cancer journey.
      Emphasis should be placed on providing support services where a high Indigenous
      population percentage resides to ensure support is maintained in rural and remote
      settings. Further efforts should be placed on relationships with Indigenous
      organisations and mainstream support services and encouraging referral from
      Indigenous liaison officers.

PMID- 22866913
TI  - Remarkable stability in patterns of blood-stage gene expression during episodes
      of non-lethal Plasmodium yoelii malaria.
AB  - BACKGROUND: Microarray studies using in vitro cultures of synchronized, blood
      stage Plasmodium falciparum malaria parasites have revealed a 'just-in-time'
      cascade of gene expression with some indication that these transcriptional
      patterns remain stable even in the presence of external stressors. However,
      direct analysis of transcription in P. falciparum blood-stage parasites obtained
      from the blood of infected patients suggests that parasite gene expression may be
      modulated by factors present in the in vivo environment of the host. The aim of
      this study was to examine changes in gene expression of the rodent malaria
      parasite, Plasmodium yoelii 17X, while varying the in vivo setting of
      replication. METHODS: Using P. yoelii 17X parasites replicating in vivo,
      differential gene expression in parasites isolated from individual mice, from
      independent infections, during ascending, peak and descending parasitaemia and in
      the presence and absence of host antibody responses was examined using P. yoelii
      DNA microarrays. A genome-wide analysis to identify coordinated changes in groups
      of genes associated with specific biological pathways was a primary focus,
      although an analysis of the expression patterns of two multi-gene families in P.
      yoelii, the yir and pyst-a families, was also completed. RESULTS: Across
      experimental conditions, transcription was surprisingly stable with little
      evidence for distinct transcriptional states or for consistent changes in
      specific pathways. Differential gene expression was greatest when comparing
      differences due to parasite load and/or host cell availability. However, the
      number of differentially expressed genes was generally low. Of genes that were
      differentially expressed, many involved biologically diverse pathways. There was
      little to no differential expression of members of the yir and pyst-a multigene
      families that encode polymorphic proteins associated with the membrane of
      infected erythrocytes. However, a relatively large number of these genes were
      expressed during blood-stage infection regardless of experimental condition.
      CONCLUSIONS: Taken together, these results indicate that 1) P. yoelii gene
      expression remains stable in the presence of a changing host environment, and 2)
      concurrent expression of a large number of the polymorphic yir and pyst-a genes,
      rather than differential expression in response to specific host factors, may in
      itself limit the effectiveness of host immune responses.

PMID- 22866915
TI  - Goniomedines A and B: unprecedented bisindole alkaloids formed through fusion of
      two indole moieties via a dihydropyran unit.
AB  - Two novel bisindole alkaloids, goniomedines A (1) and B (2), possessing an
      unprecedented quebrachamine-pleioarpamine-type skeleton, in which indole moieties
      are fused via a dihydropyran unit, were isolated from the stem bark of Gonioma
      malagasy. The structures were elucidated by comprehensive analysis of MS and NMR
      spectroscopic data. Their absolute configurations were deduced following the
      comparison of experimental and theoretically calculated ECD spectra and through
      biogenetic considerations. Goniomedine B (2) exhibited moderate activity against
      Plasmodium falciparum.

PMID- 22866916
TI  - Antioxidant carbon particles improve cerebrovascular dysfunction following
      traumatic brain injury.
AB  - Injury to the neurovasculature is a feature of brain injury and must be addressed
      to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested
      by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome
      after traumatic brain injury (TBI), most notably under conditions of hypotension.
      We report here that a new class of antioxidants, poly(ethylene glycol)
      functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon
      particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model
      when administered during resuscitation--a clinically relevant time point. Along
      with restoration of CBF, there is a concomitant normalization of superoxide and
      nitric oxide levels. Given the role of poor CBF in determining outcome, this
      finding is of major importance for improving patient health under clinically
      relevant conditions during resuscitative care, and it has direct implications for
      the current TBI/hypotension war-fighter victims in the Afghanistan and Middle
      East theaters. The results also have relevancy in other related acute
      circumstances such as stroke and organ transplantation.

PMID- 22866917
TI  - Hippo inactivation feeds tumor-initiating cells.
AB  - The Hippo pathway has emerged as a well-conserved kinase cascade controlling cell
      proliferation and survival and has recently gained much attention for its key
      activity as a tumor suppressor. In a study published in Cell, Cordenonsi and
      colleagues link TAZ, a downstream effector of the Hippo pathway, to attributes of
      putative breast cancer stem cells, epithelial-to-mesenchymal transition and cell
      polarity. 

PMID- 22866918
TI  - Decoration of graphitic surfaces with Sn nanoparticles through surface
      functionalization using diazonium chemistry.
AB  - Composites of tin nanoparticles (Sn NP) and graphene are candidate materials for
      high capacity and mechanically stable negative electrodes in rechargeable Li ion
      batteries. A uniform dispersion of Sn NP with controlled size is necessary to
      obtain high electrochemical performance. We show that the nucleation of Sn
      particles on highly ordered pyrolitic graphite (HOPG) from solution can be
      controlled by functionalizing the HOPG surface by aryl groups prior to Sn
      deposition. On the contrary, we observe heterogeneous deposition of micrometer
      sized Sn islands on HOPG subjected to oxidation prior to deposition in the same
      conditions. We demonstrate that functional groups act as nucleation sites for Sn
      NP nucleation, and that homogeneous nucleation of small particles can be achieved
      by combining surface functionalization with diazonium chemistry and appropriate
      stabilizers in solution.

PMID- 22866919
TI  - Compensatory substitutions in the HCV NS3/4A protease cleavage sites are not
      observed in patients treated unsuccessfully with telaprevir combination
      treatment.
AB  - BACKGROUND: Development of compensatory mutations within the HIV p7/p1 and p1/p6
      protease cleavage site region has been observed in HIV-infected patients treated
      with protease inhibitors. Mechanisms of fitness compensation may occur in HCV
      populations upon treatment of HCV protease inhibitors as well. FINDINGS: In this
      study, we investigated whether substitutions in protease cleavage site regions of
      HCV occur in response to a treatment regimen containing the NS3/4A protease
      inhibitor telaprevir (TVR). Evaluation of viral populations from 569 patients
      prior to treatment showed that the four NS3/4A cleavage sites were well
      conserved. Few changes in the cleavage site regions were observed in the 159
      patients who failed TVR combination treatment, and no residues displayed evidence
      of directional selection after the acquisition of TVR-resistance. CONCLUSIONS:
      Cleavage site mutations did not occur after treatment with the HCV protease
      inhibitor telaprevir.

PMID- 22866920
TI  - Vaccination with a non-human random sequence amyloid oligomer mimic results in
      improved cognitive function and reduced plaque deposition and micro hemorrhage in
      Tg2576 mice.
AB  - BACKGROUND: It is well established that vaccination of humans and transgenic
      animals against fibrillar Abeta prevents amyloid accumulation in plaques and
      preserves cognitive function in transgenic mouse models. However, autoimmune side
      effects have halted the development of vaccines based on full length human Abeta.
      Further development of an effective vaccine depends on overcoming these side
      effects while maintaining an effective immune response. RESULTS: We have
      previously reported that the immune response to amyloid oligomers is largely
      directed against generic epitopes that are common to amyloid oligomers of many
      different proteins and independent of a specific amino acid sequence. Here we
      have examined whether we can exploit this generic immune response to develop a
      vaccine that targets amyloid oligomers using a non-human random sequence amyloid
      oligomer. In order to study the effect of vaccination against generic oligomer
      epitopes, a random sequence oligomer (3A) was selected as it forms oligomers that
      react with the oligomer specific A11 antibody. Oligomer mimics from 3A peptide,
      Abeta, islet amyloid polypeptide (IAPP), and Abeta fibrils were used to vaccinate
      Tg2576 mice, which develop a progressive accumulation of plaques and cognitive
      impairment. Vaccination with the 3A random sequence antigen was just as effective
      as vaccination with the other antigens in improving cognitive function and
      reducing total plaque load (Abeta burden) in the Tg2576 mouse brains, but was
      associated with a much lower incidence of micro hemorrhage than Abeta antigens.
      CONCLUSION: These results shows that the amyloid Abeta sequence is not necessary
      to produce a protective immune response that specifically targets generic amyloid
      oligomers. Using a non-human, random sequence antigen may facilitate the
      development of a vaccine that avoids autoimmune side effects.

PMID- 22866921
TI  - Bax and Bak are required for apogossypolone, a BH3-mimetic, induced apoptosis in
      chronic lymphocytic leukemia cells.

PMID- 22866922
TI  - Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area
      of unstable malaria transmission in eastern Sudan.
AB  - BACKGROUND: Blood platelet levels are being evaluated as predictive and
      prognostic indicators of the severity of malaria infections in humans. However,
      there are few studies on platelets and Plasmodium falciparum malaria during
      pregnancy. METHODS: A case-control study was conducted at Gadarif Hospital in
      Eastern Sudan, an area characterized by unstable malaria transmission. The aim of
      the study was to investigate thrombocytopenia in pregnant women with P.
      falciparum malaria (cases) and healthy pregnant women (controls). RESULTS: The
      median (interquartile) platelet counts were significantly lower in patients with
      malaria (N = 60) than in the controls (N = 60), 61, 000 (43,000-85,000) vs.
      249,000 (204,000-300,000)/MUL, respectively, p < 0.001. However, there was no
      significant difference in the platelet counts in patients with severe P.
      falciparum malaria (N = 12) compared with those patients with uncomplicated P.
      falciparum malaria (N = 48), 68, 000 (33,000-88,000)/MUL vs. 61, 000 (45,000
      85,000)/MUL, respectively, p = 0.8. While none of the control group had
      thrombocytopenia (platelet count <75, 000/MUL), it was found that 6/12 (50%) and
      27/48 (56.2%) (p <0.001) of the patients with severe malaria and uncomplicated
      malaria had thrombocytopenia, respectively. Pregnant women with P. falciparum
      malaria, compared with the pregnant healthy control group, were at higher risk
      (OR = 10.1, 95% CI = 4.1-25.18; p < 0.001) of thrombocytopenia. Two patients
      experienced bleeding, and there was one maternal death due to cerebral malaria
      where the patient's platelet count was only 28,000/MUL. CONCLUSION: P. falciparum
      malaria is associated with thrombocytopenia in pregnant women in this setting.
      More research is needed.

PMID- 22866923
TI  - Whole-genome microarray analysis and functional characterization reveal distinct
      gene expression profiles and patterns in two mouse models of ileal inflammation.
AB  - BACKGROUND: Although a number of intestinal inflammatory conditions pertain to
      the ileum, whole-genome gene expression analyses in animal models of ileal
      inflammation are lacking to date. Therefore, we aimed to identify and
      characterize alterations in gene expression in the acutely inflamed ileum of two
      murine models of intestinal inflammation, namely intestinal schistosomiasis and
      TNBS-induced ileitis, compared to healthy controls. To this end, we used whole
      genome microarrays, followed by bioinformatics analyses to detect over
      represented Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology
      categories. RESULTS: Following screening of almost all known mouse genes and
      transcripts represented on the array, intestinal schistosomiasis and TNBS-induced
      ileitis yielded 207 and 1417 differentially expressed genes, respectively, with
      only 30 overlapping concordantly changed genes. Functional category groups
      consisting of complement and coagulation cascades, extracellular matrix (ECM)
      receptor interaction, Fc epsilon receptor I signaling pathways and protein
      activation cascade, cell adhesion categories were over-represented in the
      differential gene list of intestinal schistosomiasis. Antigen processing and
      presentation, cell adhesion molecules, ABC transporters, Toll-like receptor
      signaling pathways and response to chemical stimulus categories were over
      represented in the differential gene list of TNBS-induced ileitis. Although
      cytokine-cytokine receptor interaction, intestinal immune network for IgA
      production, focal adhesion pathways and immune, inflammatory and defense response
      categories were over-represented in the differential gene lists of both
      inflammation models, the vast majority of the associated genes and changes were
      unique to each model. CONCLUSIONS: This study characterized two models of ileal
      inflammation at a whole-genome level and outlined distinct gene expression
      profiles and patterns in the two models. The results indicate that intestinal
      schistosomiasis involves Th2 responses, complement activation, protein activation
      and enhanced ECM turnover, while TNBS-induced ileitis involves Th17 responses,
      defective antigen processing and presentation and altered Toll-like receptor
      mediated responses. Signs of an impaired epithelial barrier are apparent in both
      inflammation models. Furthermore, the comprehensive differential gene list and
      functional groups provided by this study constitute an interesting starting point
      to explore new targets and extended functional networks dealing with small bowel
      inflammation.

PMID- 22866924
TI  - Expression of DNA repair and replication genes in non-small cell lung cancer
      (NSCLC): a role for thymidylate synthetase (TYMS).
AB  - BACKGROUND: BRCA1 (B), ERCC1 (E), RRM1 (R) and TYMS (T) mRNA expression has been
      extensively studied with respect to NSCLC patient outcome upon various
      chemotherapy agents. However, these markers have not been introduced into
      clinical practice yet. One of the reasons seems to be lack of a standard approach
      for the classification of the reported high/low mRNA expression. The aim of this
      study was to determine the prognostic/predictive impact of B, E, R, T in
      routinely-treated NSCLC patients by taking into account the expression of these
      genes in the normal lung parenchyma. METHODS: B, E, R, T mRNA expression was
      examined in 276 NSCLC samples (real-time PCR). The normal range of B, E, R, T
      transcript levels was first determined in matched tumor - normal pairs and then
      applied to the entire tumor series. Four main chemotherapy categories were
      examined: taxanes-without-platinum (Tax); platinum-without-taxanes (Plat);
      taxanes/platinum doublets (Tax/Plat); and, all-other combinations. RESULTS: In
      comparison to remotely located normal lung parenchyma, B, E, R, T mRNA expression
      was generally increased in matched tumors, as well as in the entire tumor series.
      Therefore, tumors were classified as expressing normal or aberrant B, E, R, T
      mRNA. In general, no marker was associated with overall and progression free
      survival (OS, PFS). Upon multivariate analysis, aberrant intratumoral TYMS
      predicted for shorter PFS than normal TYMS in 1st line chemo-naive treated
      patients (p = 0.012). In the same setting, specific interactions were observed
      for aberrant TYMS with Plat and Tax/Plat (p = 0.003 and p = 0.006, respectively).
      Corresponding patients had longer PFS in comparison to those treated with Tax
      (Plat: HR = 0.234, 95% CI:0.108-0.506, Wald's p < 0.0001; Tax/Plat: HR = 0.242,
      95% CI:0.131-0.447, Wald's p < 0.0001). Similar results were obtained for PFS in
      1st line chemo-naive and (neo)adjuvant pre-treated patients. Adenocarcinoma,
      early disease stage, and treatment with Tax/Plat doublets independently predicted
      for prolonged OS in patients who received only one line of treatment (adjuvant or
      1st line). CONCLUSION: Classifying intratumoral B, E, R, T mRNA expression in
      comparison to normal lung may facilitate standardization of these parameters for
      prospective studies. With this approach, NSCLC patients with aberrant
      intratumoral TYMS expression will probably fare better with platinum-based
      treatments.

PMID- 22866925
TI  - Hepatitis C prevalence in Denmark -an estimate based on multiple national
      registers.
AB  - BACKGROUND: A national survey for chronic hepatitis C has not been performed in
      Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of
      chronic hepatitis C from public registers and the proportion of these patients
      who received specialized healthcare. METHODS: Patients with a diagnosis of
      chronic hepatitis C were identified from four national registers: a laboratory
      register, the Hospital Discharge Register, a clinical database of chronic viral
      hepatitis and the Register of Communicable Diseases. The total population
      diagnosed with hepatitis C was estimated by capture-recapture analysis. The
      population with undiagnosed hepatitis C was derived from the national register of
      drug users by comparing diagnosed and tested persons. RESULTS: A total of 6,935
      patients diagnosed with chronic hepatitis C were identified in the four registers
      and the estimated population diagnosed with the disease was 9,166 persons (95%
      C.I. interval 8,973 - 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the
      Danish population over 15 years of age. The prevalence was highest among persons
      40-49 years old (0.39%) and males (0.28%). It was estimated that 40% of the
      diagnosed patients lived in the capital region, and 33.5% had attended
      specialised healthcare. It was estimated that 46% of hepatitis C patients had not
      been diagnosed and the total population with chronic hepatitis C in Denmark was
      16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the
      population over 15 years of age. CONCLUSIONS: The estimated prevalence of chronic
      hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic
      hepatitis C in Denmark have been identified and among these patients, one in
      three has attended specialised care.

PMID- 22866926
TI  - Learning score function parameters for improved spectrum identification in tandem
      mass spectrometry experiments.
AB  - The identification of proteins from spectra derived from a tandem mass
      spectrometry experiment involves several challenges: matching each observed
      spectrum to a peptide sequence, ranking the resulting collection of peptide
      spectrum matches, assigning statistical confidence estimates to the matches, and
      identifying the proteins. The present work addresses algorithms to rank peptide
      spectrum matches. Many of these algorithms, such as PeptideProphet, IDPicker, or
      Q-ranker, follow a similar methodology that includes representing peptide
      spectrum matches as feature vectors and using optimization techniques to rank
      them. We propose a richer and more flexible feature set representation that is
      based on the parametrization of the SEQUEST XCorr score and that can be used by
      all of these algorithms. This extended feature set allows a more effective
      ranking of the peptide-spectrum matches based on the target-decoy strategy, in
      comparison to a baseline feature set devoid of these XCorr-based features.
      Ranking using the extended feature set gives 10-40% improvement in the number of
      distinct peptide identifications relative to a range of q-value thresholds. While
      this work is inspired by the model of the theoretical spectrum and the similarity
      measure between spectra used specifically by SEQUEST, the method itself can be
      applied to the output of any database search. Further, our approach can be
      trivially extended beyond XCorr to any linear operator that can serve as
      similarity score between experimental spectra and peptide sequences.

PMID- 22866928
TI  - Social support and weight maintenance in marriage: the interactive effects of
      support seeking, support provision, and gender.
AB  - Spouses tend to gain weight over the early years of marriage. Given that
      maintaining a healthy weight is a common goal among newlyweds, and given the
      importance of partner support to goal achievement, the current study examined
      whether the quality of spouses' supportive behaviors in early marriage predicted
      weight gain over the first 4 years of marriage. We observed 169 newlywed couples
      discussing a personal goal, coded those discussions for the quality of both
      partners' support behaviors, and assessed weight every 6 months for 4 years.
      Husbands and wives both tended to gain more weight to the extent that they
      engaged in behaviors indicative of a lack of motivation while seeking support,
      such as whining, complaining, and avoiding responsibility. Among husbands, but
      not wives, this effect was moderated by their partners' tendencies to engage in
      oppositional behaviors like criticism, confrontation, and rejection while
      providing support. These effects held controlling for marital satisfaction,
      depressive symptoms, neuroticism, and both partners' income. These findings
      demonstrate the importance of spouses' supportive behaviors for goal achievement,
      illuminate the dyadic nature of weight gain, and demonstrate the benefits of
      negativity in some contexts.

PMID- 22866930
TI  - Expectancy effects on marital interaction: rejection sensitivity as a critical
      moderator.
AB  - Positive expectancies might enhance partners' interaction quality, but these
      effects may not be equally accessible to all individuals and, if violated, might
      even increase negative affect. To address this possibility, diary data from 103
      couples, collected at three time points per day over 10 workdays, were used to
      examine whether end-of-workday expectancies of the partner's mood upon reunion
      were related to interaction experience in the evening. Rejection sensitivity was
      tested as a moderator of expectancy effects. Positive expectancies about partner
      attitudes were found to covary with more positive evaluations of interactions on
      that evening, and these associations were weaker among individuals with increased
      rejection sensitivity. Violation of daily expectancies was not associated with
      more negative interactions, but with more positive interactions. Positive
      expectancies, therefore, appear to be beneficial for relationships, particularly
      on days of negative affect, although a healthy self-concept is necessary to
      benefit from such optimistic appraisals.

PMID- 22866929
TI  - Parenting stressors and morning cortisol in a sample of working mothers.
AB  - The cortisol awakening response (CAR) is a normative rise in cortisol levels
      across the 30 minutes post awakening. Both the levels and the degree of change in
      cortisol across this time period are sensitive to the perceived challenges of the
      day and are thought to prepare the individual to meet these tasks. However,
      working parents of young children may be under unique strains at this time as
      they attempt to simultaneously care for their children while also preparing
      themselves for the workday ahead. In these analyses we examined the contributions
      of both work and parenting stress on maternal cortisol levels and awakening
      responses, and how these relationships differed on workdays compared with
      nonworkdays. To do this, saliva samples were collected from 56 working mothers
      (25% single) with a child between the ages of 2 and 4 years old (mode = 2
      children), at awakening and 30 min postawakening. Samples were collected on 4
      consecutive days-2 nonworkdays followed by 2 workdays. Analyses revealed mothers
      reporting higher levels of parenting stress had higher average a.m. cortisol on
      workdays compared with nonworkdays. Further, mothers reporting a combination of
      high job strain and high parenting stress had significantly higher cortisol
      levels and steeper CAR increases on workdays compared with nonworkdays. Findings
      are discussed by integrating knowledge from the fields of parenting stress, work
      family, and stress physiology.

PMID- 22866931
TI  - Stress spillover in early marriage: the role of self-regulatory depletion.
AB  - Stressful experiences external to a marriage (e.g., work stress, finances) are
      often associated with poor relationship functioning and lowered marital
      satisfaction, a phenomenon called stress spillover. To date, however, little
      attention has been devoted to understanding the specific mechanisms through which
      stress may lead to maladaptive relationship patterns. Drawing from theories of
      self-regulatory depletion, it was predicted that coping with external stress is
      an effortful process that consumes spouses' regulatory resources, leaving spouses
      with less energy to effectively respond to their relationship issues. The current
      study relied on a sample of newly married couples to examine whether self
      regulatory depletion may account for the link between external stress and
      relationship well-being. Couples were asked to complete a 14-day daily diary that
      assessed their daily stress, their state of self-regulatory depletion, their
      marital behaviors, and their daily marital appraisals. Within-person analyses
      revealed that, on average, couples experienced stress spillover, such that on
      days when their stress was higher than usual they reported enacting more negative
      behaviors toward their partner and endorsed less positive appraisals of the
      relationship. Further analyses confirmed that self-regulatory depletion accounted
      for a majority of these spillover effects. These findings suggest that even happy
      couples may find it difficult to engage in adaptive relationship processes under
      conditions of stress.

PMID- 22866932
TI  - Neighborhood and family intersections: prospective implications for Mexican
      American adolescents' mental health.
AB  - We present an integrated model for understanding Mexican American youth mental
      health within family, neighborhood, and cultural contexts. We combined two common
      perspectives on neighborhood effects to hypothesize that (a) parents' perceptions
      of neighborhood risk would negatively impact their children's mental health by
      disrupting key parenting and family processes, and (b) objective neighborhood
      risk would alter the effect parent and family processes had on youth mental
      health. We further incorporated a cultural perspective to hypothesize that an
      ethnic minority group's culture-specific values may support parents to
      successfully confront neighborhood risk. We provided a conservative test of the
      integrated model by simultaneously examining three parenting and family process
      variables: maternal warmth, maternal harsh parenting, and family cohesion. The
      hypothesized model was estimated prospectively in a diverse, community-based
      sample of Mexican American adolescents and their mothers (N = 749) living in the
      southwestern United States. Support for specific elements of the hypothesized
      model varied depending on the parenting or family process variable examined. For
      family cohesion results were consistent with the combined neighborhood
      perspectives. The effects of maternal warmth on youth mental health were altered
      by objective neighborhood risk. For harsh parenting, results were somewhat
      consistent with the cultural perspective. The value of the integrated model for
      research on the impacts of family, neighborhood, and cultural contexts on youth
      mental health are discussed, as are implications for preventive interventions for
      Mexican American families and youth.

PMID- 22866933
TI  - Marital satisfaction and life circumstances of grown children with autism across
      7 years.
AB  - We examined the extent to which marital satisfaction across 7 years in 199
      mothers was associated with the characteristics (gender, age, and intellectual
      disability status) of their adolescent or adult child with an autism spectrum
      disorder (ASD) and whether fluctuations in marital satisfaction covaried with the
      child's autism symptoms, health, behavior problems, and closeness in the parent
      child relationship. We also examined the impact of the departure of the adult
      child out of the family home on mothers' marital satisfaction. The effect of
      family context variables including the presence of an additional child with a
      disability, maternal education, and household income on marital satisfaction were
      also examined. We found that closeness in the mother-child relationship and
      household income had a significant effect on level of marital satisfaction, and
      that variability in the slope of mothers' marital satisfaction was significantly
      predicted by fluctuations in the behavior problems of the adolescent or adult
      child with an ASD. The grown child's departure out of the family home was not
      related to change in marital satisfaction. Interventions aimed at managing the
      behavior problems of adolescents and adults with ASDs may help strengthen
      parents' marital relationship.

PMID- 22866934
TI  - Delayed initiation of antiretroviral therapy among HIV-discordant couples in
      Kenya.
AB  - Timely initiation of antiretroviral therapy (ART) is particularly important for
      HIV-discordant couples because viral suppression greatly reduces the risk of
      transmission to the uninfected partner. To identify issues and concerns related
      to ART initiation among HIV-discordant couples, we recruited a subset of
      discordant couples participating in a longitudinal study in Nairobi to
      participate in in-depth interviews and focus group discussions about ART. Our
      results suggest that partners in HIV-discordant relationships discuss starting
      ART, yet most are not aware that ART can decrease the risk of HIV transmission.
      In addition, their concerns about ART initiation include side effects, sustaining
      an appropriate level of drug treatment, HIV/AIDS-related stigma,
      medical/biological issues, psychological barriers, misconceptions about the
      medications, the inconvenience of being on therapy, and lack of social support.
      Understanding and addressing these barriers to ART initiation among discordant
      couples is critical to advancing the HIV "treatment as prevention" agenda.

PMID- 22866936
TI  - Evaluation of an arsenic test kit for rapid well screening in Bangladesh.
AB  - Exposure to arsenic in groundwater via drinking remains unabated for millions of
      villagers in Bangladesh. Since a blanket testing campaign using test kits almost
      a decade ago, millions of new wells have been installed but not tested; thus
      affordable testing is needed. The performance of the Arsenic Econo-Quick (EQ) kit
      was evaluated by blindly testing 123 wells in Bangladesh and comparing with
      laboratory measurements; 65 wells were tested twice. A subset of the same 123
      wells was also tested using the Hach EZ kit in the field and the Digital
      Arsenator in the laboratory in Bangladesh. The EQ kit correctly determined the
      status of 110 (89%) and 113 (92%) out of 123 wells relative to the WHO guideline
      (10 MUg/L) and the Bangladesh standard (50 MUg/L), respectively. Relative to the
      WHO guideline, all misclassifications were underestimates for wells containing
      between >10 and 27 MUg/L As. Relative to the Bangladesh As standard, over- and
      underestimates were evenly distributed. Given its short reaction time of 10 min
      relative to the Hach EZ and its lower cost compared to the Arsenator, the EQ kit
      appears to have several advantages for well testing in Bangladesh and elsewhere.

PMID- 22866938
TI  - Olefin metathesis for effective polymer healing via dynamic exchange of strong
      carbon-carbon double bonds.
AB  - In this article, we demonstrate transition-metal-catalyzed olefin metathesis as a
      simple, effective method for healing polymers via dynamic exchange of strong
      carbon-carbon double bonds. Upon introducing a very low level of the Grubbs'
      second-generation Ru metathesis catalyst into cross-linked polybutadiene (PBD)
      network, the material self-heals effectively at various conditions under moderate
      pressures. In sharp contrast, catalyst-free control samples with identical
      network topology and cross-linking density show minimal healing. The healing
      efficiency of the materials was carefully investigated under different
      concentrations of the Ru catalyst, compression pressures, and temperatures. It is
      demonstrated for the first time that a bulk polymer could effectively heal via
      dynamic covalent bond formation at sub-ambient temperature. The Ru-loaded PBD
      samples not only heal well with themselves but also with control samples without
      any catalyst. Furthermore, a completely Ru-free PBD network can heal effectively
      upon simply applying a very small amount of Ru catalyst only at the fracture
      surface. The simplicity and effectiveness of this self-healing approach make it
      potentially applicable to a wide range of olefin-containing polymers.

PMID- 22866937
TI  - Randomized controlled trial of oatmeal consumption versus noodle consumption on
      blood lipids of urban Chinese adults with hypercholesterolemia.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in China
      and worldwide. Whole grain oats can reduce risk of CVD by reducing total and LDL
      cholesterol, major risk factors for CVD. While this association has been
      established in many populations, data from Asian populations is limited. Thus,
      this study investigated the impact of oat consumption on cholesterol levels in
      Chinese adults. Male and female data from this work were previously published
      separately in mandarin in two Chinese journals. The combined male and female data
      were reanalyzed and are presented here. METHODS: A randomized, controlled,
      parallel-arm study was conducted at Beijing Hospital, Beijing china. Subjects
      were adults (men and women) with mild to moderate hypercholesterolemia. The oat
      group (n=85) consumed 100 grams of instant oat cereal versus the control group
      (n=81) who consumed 100 grams of wheat flour-based noodles daily for 6 weeks.
      Laboratory and anthropometric measurements were conducted at baseline and at the
      end of the 6-week intervention. RESULTS: Dietary fiber intake increased
      significantly in the oat group compared to the control group at the end of the 6
      week intervention. Total-, LDL-cholesterol and waist circumference decreased
      significantly in the oat group compared to the control. HDL-cholesterol decreased
      significantly in the control group versus the oat group. There were no
      significant changes in blood pressure, other anthropometric or laboratory
      measures between the two groups at the end of the intervention. CONCLUSIONS:
      Instant oatmeal consumed daily for 6 weeks significantly increased fiber intake
      and decreased major risk factors for CVD in Chinese adults with
      hypercholesterolemia. Increased consumption of whole grains, including oats,
      should continue to be encouraged.

PMID- 22866939
TI  - Acetazolamide: a second wind for a respiratory stimulant in the intensive care
      unit?
AB  - Patients with chronic obstructive pulmonary disease (COPD) are affected by
      episodes of respiratory exacerbations, some of which can be severe and may
      necessitate respiratory support. Prolonged invasive mechanical ventilation is
      associated with increased mortality rates. Persistent failure to discontinue
      invasive mechanical ventilation is a major issue in patients with COPD. Pure or
      mixed metabolic alkalosis is a common finding in the intensive care unit (ICU)
      and is associated with a worse outcome. In patients with COPD, the condition is
      called post-hypercapnic alkalosis and is a complication of mechanical
      ventilation. Reversal of metabolic alkalosis may facilitate weaning from
      mechanical ventilation of patients with COPD. Acetazolamide, a non-specific
      carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse
      metabolic alkalosis. The drug is relatively safe, undesirable effects being rare.
      The compartmentalization of the different isoforms of the carbonic anhydrase
      enzyme may, in part, explain the lack of evidence of the efficacy of
      acetazolamide as a respiratory stimulant. Recent findings suggest that the
      usually employed doses of acetazolamide in the ICU may be insufficient to
      significantly improve respiratory parameters in mechanically ventilated patients
      with COPD. Randomized controlled trials using adequate doses of acetazolamide are
      required to address this issue. 

PMID- 22866940
TI  - Asymmetric synthesis of the tropane alkaloid (+)-pseudococaine via ring-closing
      iodoamination.
AB  - Ring-closing iodoamination of tert-butyl 2-hydroxy-7-[N-methyl-N-(alpha-methyl-p
      methoxybenzyl)amino]cyclohept-3-ene-1-carboxylates proceeds with concomitant loss
      of the N-alpha-methyl-p-methoxybenzyl group to give the corresponding 8
      azabicyclo[3.2.1]octane scaffolds in >99:1 dr. Subsequent elaboration of one of
      these templates provided access to (+)-pseudococaine hydrochloride, in seven
      steps and 31% overall yield from commercially available starting materials.

PMID- 22866941
TI  - Can sedentary behavior be made more active? A randomized pilot study of TV
      commercial stepping versus walking.
AB  - BACKGROUND: There is a growing problem of physical inactivity in America, and
      approximately a quarter of the population report being completely sedentary
      during their leisure time. In the U.S., TV viewing is the most common leisure
      time activity. Stepping in place during TV commercials (TV Commercial Stepping)
      could increase physical activity. The purpose of this study was to examine the
      feasibility of incorporating physical activity (PA) into a traditionally
      sedentary activity, by comparing TV Commercial Stepping during 90 min/d of TV
      programming to traditional exercise (Walking). METHODS: A randomized controlled
      pilot study of the impact of 6 months of TV Commercial Stepping versus Walking 30
      min/day in adults was conducted. 58 sedentary, overweight (body mass index 33.5
      +/- 4.8 kg/m2) adults (age 52.0 +/- 8.6 y) were randomly assigned to one of two 6
      mo behavioral PA programs: 1) TV Commercial Stepping; or 2) Walking 30 min/day.
      To help facilitate behavior changes participants received 6 monthly phone calls,
      attended monthly meetings for the first 3 months, and received monthly
      newsletters for the last 3 months. Using intent-to-treat analysis, changes in
      daily steps, TV viewing, diet, body weight, waist and hip circumference, and
      percent fat were compared at baseline, 3, and 6 mo. Data were collected in 2010
      2011, and analyzed in 2011. RESULTS: Of the 58 subjects, 47 (81%) were retained
      for follow-up at the completion of the 6-mo program. From baseline to 6-mo, both
      groups significantly increased their daily steps [4611 +/- 1553 steps/d vs. 7605
      +/- 2471 steps/d (TV Commercial Stepping); 4909 +/- 1335 steps/d vs. 7865 +/-
      1939 steps/d (Walking); P < 0.05] with no significant difference between groups.
      TV viewing and dietary intake decreased significantly in both groups. Body weight
      did not change, but both groups had significant decreases in percent body fat (3
      mo to 6-mo), and waist and hip circumference (baseline to 6-mo) over time.
      CONCLUSIONS: Participants in both the TV Commercial Stepping and Walking groups
      had favorable changes in daily steps, TV viewing, diet, and anthropometrics. PA
      can be performed while viewing TV commercials and this may be a feasible
      alternative to traditional approaches for increasing daily steps in overweight
      and obese adults. TRIAL REGISTRATION: This study is registered at
      ClinicalTrials.gov, NCT01342471.

PMID- 22866943
TI  - Electroluminescence in aligned arrays of single-wall carbon nanotubes with
      asymmetric contacts.
AB  - High quantum efficiencies and low current thresholds are important properties for
      all classes of semiconductor light emitting devices (LEDs), including nanoscale
      emitters based on single wall carbon nanotubes (SWNTs). Among the various
      configurations that can be considered in SWNT LEDs, two terminal geometries with
      asymmetric metal contacts offer the simplest solution. In this paper, we study,
      experimentally and theoretically, the mechanisms of electroluminescence in
      devices that adopt this design and incorporate perfectly aligned, horizontal
      arrays of individual SWNTs. The results suggest that exciton mediated electron
      hole recombination near the lower work-function contact is the dominant source of
      photon emission. High current thresholds for electroluminescence in these devices
      result from diffusion and quenching of excitons near the metal contact.

PMID- 22866944
TI  - The intramolecular allenolate Rauhut-Currier reaction.
AB  - An intramolecular Rauhut-Currier reaction utilizing alkynoates as the initial
      conjugate acceptor affords densely functionalized 5- and 6-membered rings from
      ynoate-enoate, ynoate-enenitrile, and alkynyl sulfone-enenitrile substrates.
      Trialkylphosphines catalyze the reaction, and TMSCN serves as a pronucelophile to
      effect turnover of the catalyst and the formation of a second C-C bond. Because
      of the highly electrophilic alkyne acceptor, this reaction yields products that
      cannot be easily accessed from the traditional Rauhut-Currier reaction.

PMID- 22866945
TI  - Expert consensus on the treatment of rheumatoid arthritis with Chinese patent
      medicines.
AB  - BACKGROUND: Chinese patent medicines (CPMs) are widely used for the treatment of
      rheumatoid arthritis (RA) in China and especially by Western biomedical doctors
      who are not well trained in TCM. Thus, it is important to create a guideline or
      an expert consensus so that the CPMs are used correctly. METHODS: The Delphi
      technique was used to generate the expert consensus. Twenty-eight (28)
      integrative medicine rheumatologists joined the consensus. A questionnaire
      regarding the general therapeutic principles, the categories, and the indications
      for the specific CPMs used for RA treatment was devised for this study. RESULTS:
      More than 80% of the experts agreed on the following therapeutic principles: CPM
      could be used to treat all patients with RA (82.10%), CPM should be used under
      the guidance of Traditional Chinese Medicine (TCM) (100%), and CPM could be used
      for active RA treatment in combination with Western medicine (WM) (85.71%), but
      could be used alone (92.86%) for the treatment of inactive RA. In addition, CPM
      and WM should be taken separately (82.14%), although the CPM could reduce the
      side-effects of the WMs if used in combination with CPM (96.43%). For the
      treatment of active RA, the CPMs were recommended by more than 50% of the experts
      included the Leigongteng Duogan tablets (85.7%), Zhengqing Dengtongning tablets
      (64.3%), and Simiao pills (53.6%). Alternatively, for the treatment of inactive
      RA, Duhuo Jisheng mixture (71.4%), Yishen Juanbi pills (53.6%), and Wangbi
      electuary (50.0%) were recommended. Total paeonia glucoside capsules were
      recommended for the active (50.0%) and inactive RA (64.3%) treatment. The
      indications of each CPM were specified according to the symptoms related to the
      TCM pattern classification. CONCLUSIONS: This expert consensus regarding the
      treatment of RA with various CPMs was formed to aid WM doctors in the correct use
      of CPMs.

PMID- 22866946
TI  - Efficacy and safety of a dual boosted protease inhibitor-based regimen,
      atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric
      population.
AB  - BACKGROUND: Although dual-boosted protease inhibitors regimen is not recommended
      in children with HIV infection, such a strategy could be useful in subjects with
      a complex resistance profile. This study was aimed at assessing the long term
      efficacy and safety of a double-boosted protease inhibitor combination,
      fosamprenavir (fAVP) and atazanavir/ritonavir (ATV/r) in a cohort of HIV-infected
      children and adolescents who had failed with nucleoside reverse transcriptase
      inhibitors. METHODS: Seven vertically infected children and adolescents who had
      previously failed highly active antiretroviral therapy and were resistant to
      nucleoside reverse transcriptase inhibitors, received a dual protease inhibitor
      (PI) regimen including fAVP plus ATV/r for 42 months. The patients were assessed
      at baseline, every month for the first 24 weeks of therapy and every 3 months
      until month 32. Physical examination, CD4+ cell count, HIV-RNA viral load, lipid
      profile and hepatic function were assessed throughout the follow up. RESULTS:
      During the study no serious adverse events were reported. CD4 absolute number
      increased over-time in all subjects. At baseline the median HIV-RNA was 6562
      cp/mL (ranging 1048 -102772 cp/mL) and rapidly decreased below the limit of
      detection (50 cp/mL) after 2 months of the new treatment and remained
      undetectable in all cases through the entire study period. At the beginning of
      the study all cases showed a normal lipid profile. During the study period, 4/7
      subjects showed total cholesterol, low density lipoprotein and triglyceride
      levels >97th cent.le for the males and 94th cent.le for the females. HDL
      cholesterol showed protective values. Hepatic enzymes remained stable during the
      entire observation, whereas total bilirubin showed toxicity II/III grade in 6/7
      subjects. No change in fat redistribution and insulin resistance was observed.
      CONCLUSION: Dual-boosted protease inhibitor therapy was virologically and
      immunologically effective and it could be considered as a possible alternative to
      a rescue regimen in children and adolescents. However, hypercholesterolemia and
      hypertriglyceridemia need close follow-up and may limit the use of this
      therapeutic option.

PMID- 22866947
TI  - Recognition of bacterial infection by innate immune sensors.
AB  - Microbial challenges to the host initiate an array of defense processes through
      the activation of innate and adaptive immunity. Innate immunity consists of
      sensors or pattern-recognition receptors (PRRs) that are expressed on immune and
      non-immune cells and sense conserved pathogen-derived molecules or pathogen
      associated molecular patterns (PAMPs) in various compartments of the host cells.
      Recognition of the PAMPs by PRRs triggers antimicrobial effector responses via
      the induction of proinflammatory cytokines and type I IFNs. Several families of
      PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like
      receptors (RLRs), and DNA sensors and their respective PAMPs have been well
      studied in innate immunity and host defense. Here, we review the recent findings
      on bacterial recognition by TLRs and NLRs and the signaling pathways activated by
      these sensors. 

PMID- 22866948
TI  - Assessment of visual disability using visual evoked potentials.
AB  - BACKGROUND: The purpose of this study is to validate the use of visual evoked
      potential (VEP) to objectively quantify visual acuity in normal and amblyopic
      patients, and determine if it is possible to predict visual acuity in disability
      assessment to register visual pathway lesions. METHODS: A retrospective chart
      review was conducted of patients diagnosed with normal vision, unilateral
      amblyopia, optic neuritis, and visual disability who visited the university
      medical center for registration from March 2007 to October 2009. The study
      included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9-42
      years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19-36 years),
      19 optic neuritis patients (19 eyes: ages 9-71 years), and 10 patients with
      visual disability having visual pathway lesions. Amplitude and latencies were
      analyzed and correlations with visual acuity (logMAR) were derived from 20 normal
      and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity
      (logMAR) of 19 optic neuritis patients confirmed relationships between visual
      acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16
      eyes from 10 patients to diagnose the presence or absence of visual disability
      using relations derived from 20 normal and 18 amblyopic eyes. RESULTS: Linear
      regression analyses between amplitude of pattern visual evoked potentials and
      visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic
      (amblyopic eyes) subjects were significant [y = -0.072x + 1.22, x: VEP amplitude,
      y: visual acuity (logMAR)]. There were no significant differences between visual
      acuity prediction values, which substituted amplitude values of 19 eyes with
      optic neuritis into function. We calculated the objective visual acuity of 16
      eyes of 10 patients to diagnose the presence or absence of visual disability
      using relations of y = -0.072x + 1.22 (-0.072). This resulted in a prediction
      reference of visual acuity associated with malingering vs. real disability in a
      range >5.77 MUV. The results could be useful, especially in cases of no obvious
      pale disc with trauma. CONCLUSIONS: Visual acuity quantification using absolute
      value of amplitude in pattern visual evoked potentials was useful in confirming
      subjective visual acuity for cutoff values >5.77 MUV in disability evaluation to
      discriminate the malingering from real disability.

PMID- 22866950
TI  - Biographical sketches.

PMID- 22866949
TI  - Bioinformatic challenges in targeted proteomics.
AB  - Selected reaction monitoring mass spectrometry is an emerging targeted proteomics
      technology that allows for the investigation of complex protein samples with high
      sensitivity and efficiency. It requires extensive knowledge about the sample for
      the many parameters needed to carry out the experiment to be set appropriately.
      Most studies today rely on parameter estimation from prior studies, public
      databases, or from measuring synthetic peptides. This is efficient and sound, but
      in absence of prior data, de novo parameter estimation is necessary.
      Computational methods can be used to create an automated framework to address
      this problem. However, the number of available applications is still small. This
      review aims at giving an orientation on the various bioinformatical challenges.
      To this end, we state the problems in classical machine learning and data mining
      terms, give examples of implemented solutions and provide some room for
      alternatives. This will hopefully lead to an increased momentum for the
      development of algorithms and serve the needs of the community for computational
      methods. We note that the combination of such methods in an assisted workflow
      will ease both the usage of targeted proteomics in experimental studies as well
      as the further development of computational approaches.

PMID- 22866952
TI  - Signaling in colon cancer stem cells.
AB  - : Colorectal cancer is the fourth most common form of cancer worldwide and
      ranks third among the cancer-related deaths in the US and other Western
      countries. It occurs with equal frequency in men and women, constituting 10% of
      new cancer cases in men and 11% in women. Despite recent advancement in
      therapeutics, the survival rates from metastatic are less than 5%. Growing
      evidence supports the contention that epithelial cancers including colorectal
      cancer, the incidence of which increases with aging, are diseases driven by the
      pluripotent, self-renewing cancer stem cells (CSCs). Dysregulation of Wnt, Notch,
      Hedgehog and/or TGF-beta signaling pathways that are involved in proliferation
      and maintenance of CSCs leads to the development of CRC. This review focuses on
      the signaling pathways relevant for CRC to understand the mechanisms leading to
      tumor progression and therapy resistance, which may help in the development of
      therapeutic strategies for CRC.

PMID- 22866953
TI  - A patient centered care plan in the EHR: improving collaboration and engagement.
AB  - Patients attempting to manage their chronic conditions require ongoing support in
      changing and adopting self-management behaviors. However, patient values, health
      goals, and action plans are not well represented in the electronic health record
      (EHR) impeding the ability of the team (MA and providers) to provide respectful,
      ongoing self-management support. We evaluated whether a team approach to using an
      EHR based patient centered care plan (PCCP) improved collaborative self
      management planning. An experimental, prospective cohort study was conducted in a
      family medicine residency clinic. The experimental group included 7 physicians
      and a medical assistant who received 2 hr of PCCP training. The control group
      consisted of 7 physicians and a medical assistant. EHR charts were analyzed for
      evidence of 8 behavior change elements. Follow-up interviews with experimental
      group patients and physicians and the medical assistant assessed their
      experiences. We found that PCCP charts had more documented behavior change
      elements than control charts in all 8 domains (p < .001). Experimental group
      physicians valued the PCCP model and suggested ways to improve its use. Patient
      feedback demonstrated support for the model. A PCCP can help team members to
      engage patients with chronic illnesses in goal setting and action planning to
      support self-management. An EHR design that stores patient values, health goals,
      and action plans may strengthen continuity and quality of care between patients
      and primary care team members. (PsycINFO Database Record (c) 2012 APA, all rights
      reserved).

PMID- 22866951
TI  - Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed
      cDNA amplicon pyrosequencing.
AB  - BACKGROUND: High-resolution HLA genotyping is a critical diagnostic and research
      assay. Current methods rarely achieve unambiguous high-resolution typing without
      making population-specific frequency inferences due to a lack of locus coverage
      and difficulty in exon-phase matching. Achieving high-resolution typing is also
      becoming more challenging with traditional methods as the database of known HLA
      alleles increases. RESULTS: We designed a cDNA amplicon-based pyrosequencing
      method to capture 94% of the HLA class I open-reading-frame with only two
      amplicons per sample, and an analogous method for class II HLA genes, with a
      primary focus on sequencing the DRB loci. We present a novel Galaxy server-based
      analysis workflow for determining genotype. During assay validation, we performed
      two GS Junior sequencing runs to determine the accuracy of the HLA class I
      amplicons and DRB amplicon at different levels of multiplexing. When 116
      amplicons were multiplexed, we unambiguously resolved 99%of class I alleles to
      four- or six-digit resolution, as well as 100% unambiguous DRB calls. The second
      experiment, with 271 multiplexed amplicons, missed some alleles, but generated
      high-resolution, concordant typing for 93% of class I alleles, and 96% for DRB1
      alleles. In a third, preliminary experiment we attempted to sequence novel
      amplicons for other class II loci with mixed success. CONCLUSIONS: The presented
      assay is higher-throughput and higher-resolution than existing HLA genotyping
      methods, and suitable for allele discovery or large cohort sampling. The
      validated class I and DRB primers successfully generated unambiguously high
      resolution genotypes, while further work is needed to validate additional class
      II genotyping amplicons.

PMID- 22866954
TI  - Azocalix[4]arene strapped calix[4]pyrrole: a confirmable fluoride sensor.
AB  - A new chromogenic fluoride sensor based on 1,3-di-p-nitrophenylazocalix[4]arene
      calix[4]pyrrole (1) was designed and synthesized. The color of the solution of
      probe 1 changed upon the addition of any F(-), CH(3)CO(2)(-), PhCO(2)(-), and
      H(2)PO(4)(-) ions. However, from these ions the highly specific sensing of F(-)
      is achieved by the addition of Ca(2+) which leads to a color change from light
      sky blue (of 1.F(-)) back to the original light orange color of 1.

PMID- 22866955
TI  - The antigenic property of the H5N1 avian influenza viruses isolated in central
      China.
AB  - BACKGROUND: Three influenza pandemics outbroke in the last century accompanied
      the viral antigen shift and drift, resulting in the change of antigenic property
      and the low cross protective ability of the existed antibody to the newly emerged
      pandemic virus, and eventually the death of millions of people. The antigenic
      characterizations of the viruses isolated in central China in 2004 and 2006-2007
      were investigated in the present study. RESULTS: Hemagglutinin inhibition assay
      and neutralization assay displayed differential antigenic characteristics of the
      viruses isolated in central China in two periods (2004 and 2006-2007). HA genes
      of the viruses mainly located in two branches in phylogeny analysis. 53 mutations
      of the deduced amino acids of the HA genes were divided into 4 patterns.
      Mutations in pattern 2 and 3 showed the main difference between viruses isolated
      in 2004 and 2006-2007. Meanwhile, most amino acids in pattern 2 and 3 located in
      the globular head of the HA protein, and some of the mutations evenly distributed
      at the epitope sites. CONCLUSIONS: The study demonstrated that a major antigenic
      drift had occurred in the viruses isolated in central China. And monitoring the
      antigenic property should be the priority in preventing the potential pandemic of
      H5N1 avian influenza virus.

PMID- 22866956
TI  - Correlates of physical activity in a population-based sample of kidney cancer
      survivors: an application of the theory of planned behavior.
AB  - BACKGROUND: Over half of kidney cancer survivors (KCS) are completely inactive
      and only a quarter are meeting physical activity (PA) guidelines. This highlights
      the need to identify and understand the determinants of PA in this understudied
      population. The purpose of this study is to determine the social cognitive
      correlates of PA intention and behavior in KCS using the Theory of Planned
      Behavior (TPB). METHODS: All 1,985 KCS diagnosed between 1996 and 2010 in
      Alberta, Canada were mailed a self-report survey that consisted of the Godin
      Leisure Time Exercise Questionnaire and standard TPB items for intention,
      planning, perceived behavioral control (PBC), affective and instrumental
      attitudes, and descriptive and injunctive norms. Standard demographic and medical
      variables were also collected. RESULTS: Completed surveys were received from 703
      of 1,654 (43%) eligible KCS. The TPB was tested using structural equation
      modelling and demonstrated an adequate-to-good fit to the data [chi2 = 256.88, p
      < .001; TLI = 0.97; CFI = 0.98; RMSEA = 0.06, 90% CI = 0.05-0.06].There were
      significant pathways to PA from PBC (beta = 0.18, p = 0.02), planning (beta =
      0.22, p < 0.01), and intention (beta = 0.31, p < 0.01); and to planning from
      intention (beta = 0.81, p < 0.01). In addition, there were significant model
      pathways to intention from instrumental attitude (beta = 0.28, p = 0.03),
      descriptive norm (beta = 0.09, p = 0.01), and PBC (beta = 0.52, p < 0.01).
      Overall, the TPB accounted for 69%, 63%, and 42% of the variance in intention,
      planning and PA, respectively. CONCLUSION: The TPB appears to be a useful model
      for explaining PA in KCS. All TPB constructs except injunctive norm and affective
      attitude were useful for explaining intention with PBC emerging as the largest
      correlate. Developing PA interventions based on the TPB may be effective in
      promoting PA in KCS and may lead to important improvements in health.

PMID- 22866957
TI  - C4-alkoxy-HPD: a potent class of synthetic modulators surpassing nature in AI-2
      quorum sensing.
AB  - Bacteria have developed cell-to-cell communication mechanisms, termed quorum
      sensing (QS), that regulate bacterial gene expression in a cell population
      dependent manner. Autoinducer-2 (AI-2), a class of QS signaling molecules derived
      from (4S)-4,5-dihydroxy-2,3-pentanedione (DPD), has been identified in both Gram
      negative and Gram-positive bacteria. Despite considerable interest in the AI-2 QS
      system, the biomolecular communication used by distinct bacterial species still
      remains shrouded. Herein, we report the synthesis and evaluation of a new class
      of DPD analogues, C4-alkoxy-5-hydroxy-2,3-pentanediones, termed C4-alkoxy-HPDs.
      Remarkably, two of the analogues were more potent QS agonists than the natural
      ligand, DPD, in Vibrio harveyi. The findings presented extend insights into
      ligand-receptor recognition/signaling in the AI-2 mediated QS system.

PMID- 22866958
TI  - Clinical review: Volume of fluid resuscitation and the incidence of acute kidney
      injury - a systematic review.
AB  - Intravenous fluids are widely administered to maintain renal perfusion and
      prevent acute kidney injury (AKI). However, fluid overload is of concern during
      AKI. Using the Pubmed database (up to October 2011) we identified all randomised
      controlled studies of goal-directed therapy (GDT)-based fluid resuscitation (FR)
      reporting renal outcomes and documenting fluid given during perioperative care.
      In 24 perioperative studies, GDT was associated with decreased risk of
      postoperative AKI (odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39 to
      0.89) but additional fluid given was limited (median: 555 ml). Moreover, the
      decrease in AKI was greatest (OR = 0.47, 95% CI = 0.29 to 0.76) in the 10 studies
      where FR was the same between GDT and control groups. Inotropic drug use in GDT
      patients was associated with decreased AKI (OR = 0.52, 95% CI = 0.34 to 0.80, P =
      0.003), whereas studies not involving inotropic drugs found no effect (OR = 0.75,
      95% CI = 0.37 to 1.53, P = 0.43). The greatest protection from AKI occurred in
      patients with no difference in total fluid delivery and use of inotropes (OR =
      0.46, 95% CI = 0.27 to 0.76, P = 0.0036). GDT-based FR may decrease AKI in
      surgical patients; however, this effect requires little overall FR and appears
      most effective when supported by inotropic drugs. 

PMID- 22866959
TI  - Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma.
AB  - BACKGROUND: An ameloblastoma is a benign odontogenic neoplasm with aggressive
      behaviour and high recurrence rates. The increased expression of matrix
      metalloproteinases (MMPs) has been reported in ameloblastomas. In the present
      study, we hypothesised that epigenetic alterations may regulate MMP expression in
      ameloblastomas. METHODS: We investigated the methylation status of the genes MMP
      2 and MMP-9 in addition to mRNA transcription and protein expression in
      ameloblastomas. Methylation analysis was performed by both methylation-specific
      polymerase chain reaction (MSP-PCR) and restriction enzyme digestion to evaluate
      the methylation profile of MMP-2 and MMP-9 in 12 ameloblastoma samples and 12
      healthy gingiva fragments, which were included as controls. Furthermore, we
      investigated the transcription levels of the genes by quantitative reverse
      transcription PCR (qRT-PCR). Zymography was performed to verify protein
      expression in ameloblastomas. RESULTS: The ameloblastomas showed a high frequency
      of unmethylated MMP-2 and MMP-9, whereas the healthy gingival samples presented a
      sharp prevalence of methylated MMPs. Higher expression levels of MMP-9 were found
      in ameloblastomas compared to healthy gingiva. However, no significant
      differences in the MMP-2 mRNA expression between groups was found. All
      ameloblastomas showed positive expression of MMP-2 and MMP-9 proteins.
      CONCLUSIONS: Our findings suggest that expression of MMP-9 is increased in
      ameloblastomas and is possibly modulated by unmethylation of the gene.

PMID- 22866960
TI  - Ultrafast predissociation mechanism of the 1Piu states of 14N2 and its
      isotopomers upon attosecond excitation from the ground state.
AB  - The computed time evolution of excited electronic and nuclear states of
      dinitrogen following a broad laser pulse excitation of the dipole allowed singlet
      Pi states is discussed. The computations use two complementary methods to solve
      the time-dependent Schrodinger equation of the molecule. The electronic evolution
      is described as spanning seven states, the three dipole-allowed singlet states
      (b,c,o(1)Pi(u)) and four triplet states (C,C',F,G(3)Pi(u)). Spin-orbit coupling
      mixes states of the two manifolds. The computed dynamics includes the attosecond
      pulse single photon pumping from the electronic ground state. The ultrafast exit
      to the continuum from the bound states that are optically excited and the large
      isotope effect on this process are used as a probe of the electron dynamics as
      coupled to the onset of the nuclear motion. For (14)N(2), prompt predissociation
      to the continuum of the repulsive C'(3)Pi(u) state is facilitated primarily by
      the b(1)Pi(u)(v = 3)-C(3)Pi(u)(v = 9) coupling whereas for (15)N(2) it is the
      b(1)Pi(u)(v = 4)-C(3)Pi(u)(v = 10) coupling term. Predissociation from the
      F(3)Pi(u) and G(3)Pi(u) states is important at the higher energies because of
      their strong coupling to the continuum.

PMID- 22866962
TI  - Quantized water access to the HIV-1 protease active site as a proposed mechanism
      for cooperative mutations in drug affinity.
AB  - The development of resistance to different drugs remains a major problem for a
      wide range of infections. In particular, combinations of specific mutations,
      which individually demonstrate no effect, exhibit significant cooperativity. Here
      we show that changes to the energy of ligand binding in different resistant HIV-1
      proteases are correlated with the creation of water binding sites in the active
      site. This correlation is conserved across two drugs (ritonavir and lopinavir).
      We propose that individual mutations induce changes in flap packing that are
      insufficient to allow water binding but in combination allow access, leading to
      the observed cooperative resistance.

PMID- 22866961
TI  - The effects of four hypocaloric diets containing different levels of sucrose or
      high fructose corn syrup on weight loss and related parameters.
AB  - BACKGROUND: The replacement of sucrose with HFCS in food products has been
      suggested as playing a role in the development of obesity as a public health
      issue. The objective of this study was to examine the effects of four equally
      hypocaloric diets containing different levels of sucrose or high fructose corn
      syrup (HFCS). METHODS: This was a randomized, prospective, double blind trial,
      with overweight/obese participants measured for body composition and blood
      chemistry before and after the completion of 12 weeks following a hypocaloric
      diet. The average caloric deficit achieved on the hypocaloric diets was 309 kcal.
      RESULTS: Reductions were observed in all measures of adiposity including body
      mass, BMI,% body fat, waist circumference and fat mass for all four hypocaloric
      groups, as well as reductions in the exercise only group for body mass, BMI and
      waist circumference. CONCLUSIONS: Similar decreases in weight and indices of
      adiposity are observed when overweight or obese individuals are fed hypocaloric
      diets containing levels of sucrose or high fructose corn syrup typically consumed
      by adults in the United States.

PMID- 22866963
TI  - Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated
      with a high prevalence of glucose disturbances and insulin resistance.
AB  - INTRODUCTION: Combined antiretroviral therapy (cART) in the treatment of HIV-1
      infection has been associated with complications, including lipodystrophy,
      hyperlipidaemia, insulin resistance (IR) and diabetes. AIMS: To compare the
      prevalence of glucose homeostasis disturbances and IR in HIV patients on cART
      according to the presence of lipodystrophy (defined clinically and by Fat Mass
      Ratio) and different patterns of fat distribution and to establish their
      associations. DESIGN: Cross-sectional cohort study. METHODS: We evaluated body
      composition and IR and insulin sensitivity indexes in 345 HIV-infected adults.
      RESULTS: Patients with clinical lipodystrophy (CL) had higher plasma glucose
      levels than patients without CL, without significant differences in plasma
      insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with
      lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c,
      HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without
      differences in HOMA-B. Higher insulin resistance (HOMA-IR >= 4) was present in
      patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy
      had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy.
      Significant associations between HOMA-IR and total, central and
      central/peripheral fat evaluated by CT at abdominal level were found and no
      association between HOMA-IR and peripheral fat. Association between HOMA-IR and
      total and trunk fat but no association with leg and arm fat (evaluated by DXA)
      was found. CONCLUSIONS: IR and glucose disturbances were significantly increased
      in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to
      be a more sensitive determinant of insulin resistance and glucose disturbances
      than clinical definition.

PMID- 22866964
TI  - Telmisartan or valsartan alone or in combination with hydrochlorothiazide: a
      review.
AB  - The aim of this review was to compare telmisartan and valsartan in the treatment
      of hypertension. PubMed searches were conducted to identify randomized trials (n
      = 14) comparing the two agents, alone or combined with hydrochlorothiazide. With
      one exception, all studies with blood pressure reduction as primary endpoint
      showed significantly greater reductions with telmisartan than with valsartan.
      Other studies showed that telmisartan was associated with greater improvements in
      metabolic measures and inflammatory markers than valsartan. These findings
      suggest that pharmacologic differences between telmisartan and valsartan may
      translate into clinically relevant differences between the two drugs in the
      management of hypertension.

PMID- 22866966
TI  - Statin drug interactions and related adverse reactions.
AB  - INTRODUCTION: Statin monotherapy is generally well tolerated, with a low
      frequency of adverse events. The most important adverse effects associated with
      statins are myopathy and an asymptomatic increase in hepatic transaminases, both
      of which occur infrequently. Because statins are prescribed on a long-term basis,
      their possible interactions with other drugs deserve particular attention, as
      many patients will typically receive pharmacological therapy for concomitant
      conditions during the course of statin treatment. AREAS COVERED: This review
      summarizes the pharmacokinetic properties of statins and emphasizes their
      clinically relevant drug interactions and related adverse reactions. EXPERT
      OPINION: Avoiding drug-drug interactions and consequent adverse drug reactions is
      essential in order to optimize compliance, and thus improve the treatment of
      patients at high cardiovascular risk. The different pharmacokinetic profiles
      among statins should be carefully considered, in order to understand the possible
      spectrum of drug interactions. The growing trend toward earlier statin treatment
      for the prevention of cardiovascular disease means that physicians must
      anticipate future polypharmacy when their patients require additional medications
      for comorbid conditions.

PMID- 22866967
TI  - Aspirin inhibits oxidant stress, reduces age-associated functional declines, and
      extends lifespan of Caenorhabditis elegans.
AB  - AIMS: Oxidative stress and inflammation are leading risk factors for age
      associated functional declines. We assessed aspirin effects on endogenous
      oxidative-stress levels, lifespan, and age-related functional declines, in the
      nematode Caenorhabditis elegans. RESULTS: Both aspirin and its salicylate moiety,
      at nontoxic concentrations (0.5-1 mM), attenuated endogenous levels of reactive
      oxygen species (p<0.001), and upregulated antioxidant genes encoding superoxide
      dismutases (especially sod-3, p<0.001), catalases (especially ctl-2, p<0.0001),
      and two glutathione-S-transferases (gst-4 and gst-10; each p<0.005). Aspirin, and
      to a lesser degree salicylate, improved survival of hydrogen peroxide, and in the
      absence of exogenous stress aspirin extended lifespan by 21%-23% (each p<10(-9)),
      while salicylate added 14% (p<10(-6)). Aspirin and salicylate delayed age
      dependent declines in motility and pharyngeal pumping (each p<0.005), and
      decreased intracellular protein aggregation (p<0.0001)-all established markers of
      physiological aging-consistent with slowing of the aging process. Aspirin fails
      to improve stress resistance or lifespan in nematodes lacking DAF-16, implying
      that it acts through this FOXO transcription factor. INNOVATION: Studies in mice
      and humans suggest that aspirin may protect against multiple age-associated
      diseases by reducing all-cause mortality. We now demonstrate that aspirin
      markedly slows many measures of aging in the nematode. CONCLUSIONS: Aspirin
      treatment is associated with diminished endogenous oxidant stress and enhanced
      resistance to exogenous peroxide, both likely mediated by activation of
      antioxidant defenses. Our evidence indicates that aspirin attenuates insulin-like
      signaling, thus protecting against oxidative stress, postponing age-associated
      functional declines and extending C. elegans lifespan under benign conditions.

PMID- 22866968
TI  - Electrochemical transduction on self-assembled monolayers: are covalent links
      essential?
AB  - Electrochemical transduction without covalent links between redox and complexant
      units in a complexing self-assembled monolayer has been established. The results
      demonstrate that transduction depends on the crown ether/ferrocene ratio and
      appears to be tunable.

PMID- 22866969
TI  - Plasma resistin levels are associated with insulin resistance in older Japanese
      men from a rural village.
AB  - BACKGROUND: The role of resistin in the pathophysiology of insulin resistance in
      human is controversial and different in men and women. Thus, the discrepancy
      among previous reports may be resolved by gender-specific analysis of a large
      number of participants. METHODS: From a single community, we recruited 746 men
      (mean age, 60+/-14 years) and 1033 women (63+/-12 years) during their annual
      health examination. We investigated whether plasma resistin levels are associated
      with insulin resistance evaluated by homeostasis of model assessment of insulin
      resistance (HOMA-IR) according to gender. RESULTS: Resistin levels were
      significantly correlated with HOMA-IR in men, but not in women. Analysis of
      covariance showed that two regression lines were significantly different
      (F=9.941, P=0.002). Multiple linear regression analyses for resistin showed that
      the resistin levels (beta=0.124, P<0.001) were independently and significantly
      associated with HOMA-IR as well as body mass index (BMI), alcohol consumption,
      smoking status, uric acid, gamma-glutamyltransferase (GGT), and high molecular
      weight (HMW) adiponectin only in men and not in women. The interaction between
      gender and resistin level (F=11.50, P<0.001) was also a significant and
      independent determinant for HOMA-IR as well as gender, BMI, alcohol consumption,
      smoking status, uric acid, GGT, HMW adiponectin, and resistin. CONCLUSIONS: These
      results suggest that plasma resistin levels are associated with insulin
      resistance in older Japanese men.

PMID- 22866970
TI  - Burkitts's lymphoma--an atypical presentation.
AB  - BACKGROUND: In female adolescents and young adults, malignancies of the genital
      tract are the most frequent type of cancer, closely followed by Hodgkin's and non
      Hodgkin's lymphomas. CASE PRESENTATION: We report an unusual case of sporadic
      Burkitt's lymphoma (BL) presenting with massive bilateral ovarian infiltration,
      peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the
      intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by
      endoscopy of the upper gastrointestinal tract. With intensive chemotherapy,
      complete remission was rapidly achieved, without life-threatening tumor lysis
      syndrome. CONCLUSION: Besides metastatic gastric adenocarcinoma, BL is an
      important differential diagnosis in adolescents presenting with Krukenberg tumor.

PMID- 22866971
TI  - Evaluation of a surgical service in the chronic phase of a refugee camp: an
      example from the Thai-Myanmar border.
AB  - BACKGROUND: Published literature on surgical care in refugees tends to focus on
      the acute ('emergent') phase of crisis situations. Here we posit that there is a
      substantial burden of non-acute morbidity amenable to surgical intervention among
      refugees in the 'chronic' phase of crisis situations. We describe surgery for non
      acute conditions undertaken at Mae La Refugee Camp, Thailand over a two year
      period. METHODS: Surgery was performed by a general surgeon in a dedicated room
      of Mae La Refugee Camp over May 2005 to April 2007 with minimal instruments and
      staff. We obtained the equivalent costs for these procedures if they were done at
      the local Thai District General Hospital. We also acquired the list (and costs)
      of acute surgical referrals to the District General Hospital over September 2006
      to December 2007. RESULTS: 855 operations were performed on 847 patients in Mae
      La Refugee Camp (60.1% sterilizations, 13.3% 'general surgery', 5.6%
      'gynaecological surgery', 17.4% 'mass excisions', 3.5% 'other'). These procedures
      were worth 2,207,500 THB (75,683.33 USD) at costs quoted by the District General
      Hospital. Total cost encountered for these operations (including staff costs,
      consumables, anaesthesia and capital costs such as construction) equaled
      1,280,000 THB (42,666 USD). Pertaining to acute surgical referrals to District
      General hospital: we estimate that 356,411.96 THB (11,880.40 USD) worth of
      operations over 14 months were potentially preventable if these cases had been
      operated at an earlier, non-acute state in Mae La Refugee Camp. CONCLUSIONS: A
      considerable burden of non-acute surgical morbidity exists in 'chronic' refugee
      situations. An in-house general surgical service is found to be cost-effective in
      relieving some of this burden and should be considered by policy makers as a
      viable intervention.

PMID- 22866972
TI  - Prevalence and correlates of complementary and alternative medicine services use
      in low-income African Americans and whites: a report from the Southern Community
      Cohort Study.
AB  - OBJECTIVES: This study aimed to examine the prevalence, trends, and correlates of
      practitioner-based complementary and alternative medicine (CAM) services use
      according to race in a socioeconomically disadvantaged population. DESIGN:
      Included in this cross-sectional analysis were 50,176 African Americans (AAs) and
      19,038 whites enrolled into the Southern Community Cohort Study from March 2002
      through September 2009. Logistic regression models were used to calculate odds
      ratios (ORs) and 95% confidence intervals (CIs) of CAM services use associated
      with participant characteristics. OUTCOME MEASURES: Outcomes include the
      prevalence of and trends in use of CAM services during 2002-2009 and correlates
      of use by race. RESULTS: CAM services use during 2002-2009 was greater among
      whites (11.7%) than among AAs (8.5%), but no significant temporal trends within
      the 8-year period were observed. The significant associations were observed for
      CAM services use with higher educational attainment (OR 1.78, 95% CI: 1.61-1.96
      for college versus less than high school), household income (OR 1.61, 95% CI:
      1.44-1.81 for >=$50,000 versus <$15,000), and having a history of a chronic
      disease (OR 1.34, 95% CI: 1.21-1.47) among both AAs and whites. Significant
      differences in findings between AAs and whites were seen for age (with a sharp
      decline in use with older age among AAs but not whites), sex (with the excess of
      female users more striking among whites), employment (with the unemployed among
      AAs but not whites more likely to be users), alcohol consumption (with white but
      not AA drinkers more likely to report CAM services use), and cigarette smoking
      status (with negative association of use with current smokers more striking among
      whites). CONCLUSIONS: CAM services use is associated with sociodemographic and
      health-related factors, and racial differences in such use exist. The descriptive
      findings of this study help supplement the limited information on CAM use among
      low-income and minority populations in the United States.

PMID- 22866974
TI  - Vitamin D status, dietary intake, and bone turnover in female Soldiers during
      military training: a longitudinal study.
AB  - BACKGROUND: Vitamin D is an essential nutrient for maintaining bone health, to
      include protecting against stress fracture during periods of rapid bone turnover.
      The objective of this longitudinal, observational study was to assess vitamin D
      status, biomarkers of bone turnover, and vitamin D and calcium intake in female
      Soldiers (n = 91) during US Army basic combat training (BCT). METHODS:
      Anthropometric, biological and dietary intake data were collected at wk 0, 3, 6,
      and 9 of the 10 wk BCT course. Mixed models repeated measures ANOVAs were used to
      assess main effects of time, race, and time-by-race interactions. RESULTS: White
      volunteers experienced a decrease in serum 25(OH)D levels, whereas non-white
      volunteers experienced an increase during BCT. However, serum 25(OH)D levels were
      lower in non-whites than whites at all timepoints (P-interaction < 0.05). Group
      mean PTH levels increased (P < 0.05) during the first 3 wk of training, remained
      elevated for the duration of BCT, and were higher in non-whites compared to
      whites (P-race < 0.05). Biomarkers of both bone formation (bone alkaline
      phosphatase and procollagen I N-terminal peptide) and resorption (tartrate
      resistant acid phosphatase and C-terminal telopeptide) increased (P < 0.05)
      during BCT, indicating increased bone turnover. Estimated daily intakes of
      vitamin D and calcium were below recommended levels (15 MUg and 1000 mg/day,
      respectively), both before (group mean +/- SEM; 3.9 MUg/d +/- 0.4 and 887 mg/d +/
      67) and during BCT (4.1 MUg/d +/- 0.3 and 882 mg/d +/- 51). CONCLUSIONS: These
      findings demonstrate that female Soldiers experience dynamic changes in vitamin D
      status coupled with increased bone turnover and potentially inadequate vitamin D
      and calcium intake during military training.

PMID- 22866973
TI  - The peritoneal macrophage inflammatory profile in cirrhosis depends on the
      alcoholic or hepatitis C viral etiology and is related to ERK phosphorylation.
AB  - BACKGROUND: The development of ascites in cirrhotic patients generally heralds a
      deterioration in their clinical status. A differential gene expression profile
      between alcohol- and hepatitis C virus (HCV)-related cirrhosis has been described
      from liver biopsies, especially those associated with innate immune responses.
      The aim of this work was to identify functional differences in the inflammatory
      profile of monocyte-derived macrophages from ascites in cirrhotic patients of
      different etiologies in an attempt to extrapolate studies from liver biopsies to
      immune cells in ascites. To this end 45 patients with cirrhosis and non-infected
      ascites, distributed according to disease etiology, HCV (n=15) or alcohol (n=30)
      were studied. Cytokines and the cell content in ascites were assessed by ELISA
      and flow cytometry, respectively. Cytokines and ERK phosphorylation in peritoneal
      monocyte-derived macrophages isolated and stimulated in vitro were also
      determined. RESULTS: A different pattern of leukocyte migration to the peritoneal
      cavity and differences in the primed status of macrophages in cirrhosis were
      observed depending on the viral or alcoholic etiology. Whereas no differences in
      peripheral blood cell subpopulations could be observed, T lymphocyte, monocyte
      and polymorphonuclear cell populations in ascites were more abundant in the HCV
      than the alcohol etiology. HCV-related cirrhosis etiology was associated with a
      decreased inflammatory profile in ascites compared with the alcoholic etiology.
      Higher levels of IL-10 and lower levels of IL-6 and IL-12 were observed in
      ascitic fluid from the HCV group. Isolated peritoneal monocyte-derived
      macrophages maintained their primed status in vitro throughout the 24 h culture
      period. The level of ERK1/2 phosphorylation was higher in ALC peritoneal
      macrophages at baseline than in HCV patients, although the addition of LPS
      induced a greater increase in ERK1/2 phosphorylation in HCV than in ALC patients.
      CONCLUSIONS: The macrophage inflammatory status is higher in ascites of alcohol
      related cirrhotic patients than in HCV-related patients, which could be related
      with differences in bacterial translocation episodes or regulatory T cell
      populations. These findings should contribute to identifying potential prognostic
      and/or therapeutic targets for chronic liver diseases of different etiology.

PMID- 22866975
TI  - Getting to the heart of the matter: a diary study of swimmers' appraisals of
      organisational stressors.
AB  - We explored sport performers' cognitive appraisals of organisational stressors.
      The relevant demands and transactional alternatives that athletes experience in
      relation to the situational properties were identified. Thirteen national
      standard swimmers completed semi-structured, interval-contingent daily diaries
      for a 28-day period. A combination of inductive and deductive content analysis
      was used to organise and analyse the diary entries with a focus on the following
      areas: organisational stressors, their underlying situational properties, and the
      swimmers' transactional alternatives. One hundred and thirty-one of the
      organisational stressors were appraised as threat, 41 as challenge, and 83 as
      harm/loss. Support was found for the majority of Lazarus and Folkman's (1984)
      situational properties with the only exception being temporal uncertainty.
      Imminence was associated with the greatest number of threat appraisals (47),
      novelty was associated with the greatest number of challenge appraisals (17), and
      duration was associated with the greatest number of harm/loss appraisals (22). It
      is concluded that appraisal plays a pivotal role in sport performers' experiences
      of their organisational environment. Swimmers' transactional alternatives are
      influenced by the situational properties of the stressors encountered.

PMID- 22866976
TI  - Acute kidney injury and residual renal function.
AB  - Acute kidney injury (AKI) occurring in patients admitted to the ICU may result in
      impaired renal function on long-term follow-up after ICU discharge. The damage
      induced by subclinical or manifest episodes of AKI may, in fact, produce an
      irreversible loss of a variable amount of renal mass with deleterious effects on
      overall renal function. This may be the case even though baseline glomerular
      filtration rate appears to return to normal but renal reserve is impaired. This
      may have an important effect on long-term outcomes, including progression to
      chronic kidney disease. Acute kidney insults should not be considered as isolated
      episodes but rather a sequence of progressive events that can lead to progressive
      deterioration of kidney tissue and eventual declines in renal function. 

PMID- 22866978
TI  - Control of nuclear dynamics with strong ultrashort laser pulses.
AB  - We demonstrate how the evolution of a bound vibrational wave packet can be
      controlled by a strong field laser pulse. We consider two different control
      schemes within the same molecule (CH(2)BrI): reshaping of the wave packet via
      strong field population transfer ("hole burning"), and redirecting its trajectory
      by dressing the potential energy surface on which the wave packet evolves
      ("photon locking"). Our measurements are compared with calculations using wave
      packet propagation on ab initio potential energy surfaces.

PMID- 22866977
TI  - Aminonaphthalene 2-cyanoacrylate (ANCA) probes fluorescently discriminate between
      amyloid-beta and prion plaques in brain.
AB  - A major challenge for diagnosing and monitoring the progression of amyloid-based
      diseases is the capability to distinguish between amyloid deposits that are
      associated with related, but distinctly different, diseases. Here, we demonstrate
      that aminonaphthalenyl 2-cyanoacrylate-based probes can fluorescently
      discriminate between different types of amyloid deposits in brain. The
      discriminating capability of these molecular rotors is due to the stabilization
      of the ground versus excited states of these probes as a function of the polarity
      of their microenvironment (i.e., within the binding pocket on the amyloid). This
      property makes it possible, for the first time, to estimate the inherent static
      relative permittivity (epsilon(0)) of the binding pocket of each amyloid within
      tissue. The capability to selectively follow the deposition of specific amyloids
      in tissue may provide important information for therapeutic development that is
      not readily accessible from currently available technology.

PMID- 22866979
TI  - Mineralocorticoid receptor antagonists for the treatment of hypertension and
      diabetic nephropathy.

PMID- 22866980
TI  - Using stochastic modelling to identify unusual continuous glucose monitor
      measurements and behaviour, in newborn infants.
AB  - BACKGROUND: Abnormal blood glucose (BG) concentrations have been associated with
      increased morbidity and mortality in both critically ill adults and infants.
      Furthermore, hypoglycaemia and glycaemic variability have both been independently
      linked to mortality in these patients. Continuous Glucose Monitoring (CGM)
      devices have the potential to improve detection and diagnosis of these glycaemic
      abnormalities. However, sensor noise is a trade-off of the high measurement rate
      and must be managed effectively if CGMs are going to be used to monitor, diagnose
      and potentially help treat glycaemic abnormalities. AIM: To develop a tool that
      will aid clinicians in identifying unusual CGM behaviour and highlight CGM data
      that potentially need to be interpreted with care. METHODS: CGM data and BG
      measurements from 50 infants at risk of hypoglycaemia were used. Unusual CGM
      measurements were classified using a stochastic model based on the kernel density
      method and historical CGM measurements from the cohort. CGM traces were colour
      coded with very unusual measurements coloured red, highlighting areas to be
      interpreted with care. A 5-fold validation of the model was Monte Carlo simulated
      25 times to ensure an adequate model fit. RESULTS: The stochastic model was
      generated using ~67,000 CGM measurements, spread across the glycaemic range ~2-10
      mmol/L. A 5-fold validation showed a good model fit: the model 80% confidence
      interval (CI) captured 83% of clinical CGM data, the model 90% CI captured 91% of
      clinical CGM data, and the model 99% CI captured 99% of clinical CGM data. Three
      patient examples show the stochastic classification method in use with 1) A
      stable, low variability patient which shows no unusual CGM measurements, 2) A
      patient with a very sudden, short hypoglycaemic event (classified as unusual),
      and, 3) A patient with very high, potentially un-physiological, glycaemic
      variability after day 3 of monitoring (classified as very unusual). CONCLUSIONS:
      This study has produced a stochastic model and classification method capable of
      highlighting unusual CGM behaviour. This method has the potential to classify
      important glycaemic events (e.g. hypoglycaemia) as true clinical events or sensor
      noise, and to help identify possible sensor degradation. Colour coded CGM traces
      convey the information quickly and efficiently, while remaining computationally
      light enough to be used retrospectively or in real-time.

PMID- 22866981
TI  - How do postgraduate GP trainees regulate their learning and what helps and
      hinders them? A qualitative study.
AB  - BACKGROUND: Self-regulation is essential for professional development. It
      involves monitoring of performance, identifying domains for improvement,
      undertaking learning activities, applying newly learned knowledge and skills and
      self-assessing performance. Since self-assessment alone is ineffective in
      identifying weaknesses, learners should seek external feedback too. Externally
      regulated educational interventions, like reflection, learning portfolios,
      assessments and progress meetings, are increasingly used to scaffold self
      regulation.The aim of this study is to explore how postgraduate trainees regulate
      their learning in the workplace, how external regulation promotes self-regulation
      and which elements facilitate or impede self-regulation and learning. METHODS: In
      a qualitative study with a phenomenologic approach we interviewed first- and
      third-year GP trainees from two universities in the Netherlands. Twenty-one
      verbatim transcripts were coded. Through iterative discussion the researchers
      agreed on the interpretation of the data and saturation was reached. RESULTS:
      Trainees used a short and a long self-regulation loop. The short loop took one
      week at most and was focused on problems that were easy to resolve and needed
      minor learning activities. The long loop was focused on complex or recurring
      problems needing multiple and planned longitudinal learning activities. External
      assessments and formal training affected the long but not the short loop. The
      supervisor had a facilitating role in both loops. Self-confidence was used to
      gauge competence.Elements influencing self-regulation were classified into three
      dimensions: personal (strong motivation to become a good doctor), interpersonal
      (stimulation from others) and contextual (organizational and educational
      features). CONCLUSIONS: Trainees did purposefully self-regulate their learning.
      Learning in the short loop may not be visible to others. Trainees should be
      encouraged to actively seek and use external feedback in both loops. An important
      question for further research is which educational interventions might be used to
      scaffold learning in the short loop. Investing in supervisor quality remains
      important, since they are close to trainee learning in both loops.

PMID- 22866983
TI  - beta-Diketiminate germylene-supported pentafluorophenylcopper(I) and -silver(I)
      complexes [LGe(Me)(CuC6F5)n]2 (n = 1, 2), LGe[C(SiMe3)N2]AgC6F5, and
      {LGe[C(SiMe3)N2](AgC6F5)2}2 (L = HC[C(Me)N-2,6-iPr2C6H3]2): synthesis and
      structural characterization.
AB  - Reactions of LGeMe (L = HC[C(Me)N-2,6-iPr(2)C(6)H(3)](2)) with 0.25 or 0.5 equiv
      of (CuC(6)F(5))(4) gave the products [LGe(Me)CuC(6)F(5)](2) (1) and
      [LGe(Me)(CuC(6)F(5))(2)](2) (2), respectively. In situ formed 1 reacted with 0.5
      equiv of (CuC(6)F(5))(4) to give 2 on the basis of NMR ((1)H and (19)F) spectral
      measurements. Conversely, 2 was converted into 1 by treatment with 2 equiv of
      LGeMe. Reactions of LGeC(SiMe(3))N(2) with 1 or 2 equiv of AgC(6)F(5).MeCN
      produced the corresponding compounds LGe[C(SiMe(3))N(2)]AgC(6)F(5) (3) and
      {LGe[C(SiMe(3))N(2)](AgC(6)F(5))(2)}(2) (4). Similarly, 3 was converted into 4 by
      treatment with 1 equiv of AgC(6)F(5).MeCN and 4 converted into 3 by reaction with
      2 equiv of LGeC(SiMe(3))N(2). X-ray crystallographic studies showed that 1
      contains a rhombically bridged (CuC(6)F(5))(2), while 2 has a chain-structurally
      aggregated (CuC(6)F(5))(4), both supported by LGeMe. Correspondingly, 3 showed a
      terminally bound AgC(6)F(5) and 4 a chain-structurally aggregated
      (AgC(6)F(5))(4), both supported by LGeC(SiMe(3))N(2). Photophysical studies
      proved that the Ge-Cu metal-metalloid donor-acceptor bonding persists in
      solutions of 1 and 2 and Ge-Ag donor-acceptor bonding in solutions of 3 and 4 as
      a result of the clear migration of their emission bands compared to those of the
      corresponding starting materials. Low-temperature (-50  degrees C) (19)F NMR
      spectral measurements detected dissociation of 1, 2, and 4 by the aggregation
      part of the CuC(6)F(5) or AgC(6)F(5) entities in solution. These results provide
      good support for pentafluorophenylcopper(I) or -silver(I) species having beta
      diketiminate germylene as a donor because of its remarkably electronic and steric
      character.

PMID- 22866982
TI  - Non structural protein of avian influenza A (H11N1) virus is a weaker suppressor
      of immune responses but capable of inducing apoptosis in host cells.
AB  - BACKGROUND: The Non-Structural (NS1) protein of Influenza A viruses is an
      extensively studied multifunctional protein which is commonly considered as key
      viral component to fight against host immune responses. Even though there has
      been a lot of studies on the involvement of NS1 protein in host immune responses
      there are still ambiguities regarding its role in apoptosis in infected cells.
      Interactions of NS1 protein with host factors, role of NS1 protein in regulating
      cellular responses and apoptosis are quite complicated and further studies are
      still needed to understand it completely. RESULTS: NS1 genes of influenza
      A/Chicken/India/WBNIV2653/2008 (H5N1) and A/Aquatic bird/India/NIV
      17095/2007(H11N1) were cloned and expressed in human embryonic kidney (293T)
      cells. Microarray based approach to study the host cellular responses to NS1
      protein of the two influenza A viruses of different pathogenicity showed
      significant differences in the host gene expression profile. NS1 protein of H5N1
      resulted in suppression of IFN-beta mediated innate immune responses, leading to
      down-regulation of the components of JAK-STAT pathway like STAT1 which further
      suppressed the expression of pro-inflammatory cytokines like CXCL10 and CCL5. The
      degree of suppression of host immune genes was found considerable with NS1
      protein of H11N1 but was not as prominent as with H5N1-NS1. TUNEL assay analyses
      were found to be positive in both the NS1 transfected cells indicating both H5N1
      as well as H11N1 NS1 proteins were able to induce apoptosis in transfected cells.
      CONCLUSIONS: We propose that NS1 protein of both H5N1 and H11N1 subtypes of
      influenza viruses are capable of influencing host immune responses and possess
      necessary functionality to support apoptosis in host cells. H11N1, a low
      pathogenic virus without any proven evidence to infect mammals, contains a highly
      potential NS1 gene which might contribute to greater virus virulence in different
      gene combinations.

PMID- 22866984
TI  - Does the adoption of EUCAST susceptibility breakpoints affect the selection of
      antimicrobials to treat acute community-acquired respiratory tract infections?
AB  - BACKGROUND: In several European Countries, by the end of 2012, CLSI guidelines
      will be replaced by EUCAST. We compared antimicrobial susceptibility results of a
      large number of respiratory pathogens using both EUCAST and previously adopted
      CLSI criteria to evaluate the impact on susceptibility patterns and the possible
      consequences that could occur in clinical practice due to this replacement.For S.
      pyogenes and S. aureus, the interpretation of susceptibility data using the
      EUCAST criteria did not produce relevant changes in comparison to CLSI.Against S.
      pneumoniae, more restrictive EUCAST breakpoints could lead to increased
      benzylpenicillin and/or amoxicillin-clavulanate resistance rates, which in turn
      could translate in increased dosages of these antibiotics or usage of alternative
      agents for respiratory tract infections.Against S. pneumoniae, M. catarrhalis and
      H. influenzae, cefuroxime-axetil and cefaclor produced the most divergent results
      depending on the breakpoints adopted and these striking differences could lead to
      the revision of those guidelines suggesting these two cephalosporins as
      alternatives in the management of upper respiratory tract infections. DISCUSSION:
      Many differences exist between CLSI and EUCAST breakpoints. However, only in a
      few cases do these differences translate in major interpretive category
      discrepancies. In countries adopting more restrictive EUCAST breakpoints,
      clinicians should be aware of these discrepancies and that they could be faced
      with antibiotic-resistant respiratory pathogens more frequently than before.
      SUMMARY: The interpretive discrepancies between EUCAST and CLSI suggest that the
      discussion on the management of community-acquired respiratory tract infections
      is still open and further studies are desirable to better define the role of some
      antibiotics.

PMID- 22866985
TI  - Vascular effects of aqueous extract of Chamaemelum nobile: in vitro
      pharmacological studies in rats.
AB  - This study aims to evaluate the in vitro vasorelaxant effect of C. nobile aqueous
      extract. We use aortic ring isolated from Wistar rats and aqueous C. nobile
      extract at doses of 5, 10 and 20 mg/ml. Incubation of aqueous C. nobile extract
      for 30 minutes produced a significant shift of the dose-response curve to
      norepinephrine (NE) (10(-8) to 10(-5) M) (p < 0.001). This study demonstrates
      that aqueous C. nobile extract possesses in vitro vasorelaxant effect.

PMID- 22866987
TI  - Versatile 2,7-substituted pyrene synthons for the synthesis of pyrene-fused
      azaacenes.
AB  - A new synthetic route to prepare a series of versatile 2,7-substituted pyrene
      synthons for the synthesis of pyrene-fused azaacenes is described. By using such
      synthons, a library of eight pyrene-fused azacenes with different electronic
      structures and in most cases with enhanced solubility has been synthesized and
      characterized.

PMID- 22866986
TI  - Processing speed and executive abilities in children with phenylketonuria.
AB  - OBJECTIVE: Phenylketonuria (PKU) is a hereditary metabolic disorder that often
      results in neuropsychological impairment, even in individuals treated early and
      continuously. This study was conducted to examine processing speed, variability
      in processing speed, and the relationship between processing speed variables and
      executive abilities in children with early and continuously treated PKU. METHOD:
      Participants were 42 children with PKU and 81 typically developing children from
      7 to 18 years of age. Children completed 3 computerized reaction time (RT) tasks
      (simple RT, go/no-go, stimulus-response compatibility) and 7 tasks assessing
      executive abilities (working memory, inhibitory control, strategic processing).
      RESULTS: Performance of children with PKU was significantly slower and more
      variable than that of controls across the 3 tasks administered. When age was
      considered, it was shown that processing speed improved with age to a comparable
      degree for both groups. Variability in processing speed, however, decreased more
      with age for the PKU than control group, reflecting the fact that variability in
      younger, but not older, children with PKU was greater than that of controls. With
      regard to executive abilities, processing speed and variability contributed to
      performance on most, but not all, executive tasks; and after controlling for
      processing speed and variability, executive impairments were still identified in
      working memory and inhibitory control (not strategic processing). CONCLUSIONS:
      These findings indicate that information processing is slower and less efficient
      in children with PKU. In addition, processing speed and variability contribute to
      some, but not all, of the impairments in executive abilities observed in children
      with PKU.

PMID- 22866988
TI  - Nonionic, water self-dispersible "hairy-rod" poly(p-phenylene)-g-poly(ethylene
      glycol) copolymer/carbon nanotube conjugates for targeted cell imaging.
AB  - The generation and fabrication of nanoscopic structures are of critical
      technological importance for future implementations in areas such as nanodevices
      and nanotechnology, biosensing, bioimaging, cancer targeting, and drug delivery.
      Applications of carbon nanotubes (CNTs) in biological fields have been impeded by
      the incapability of their visualization using conventional methods. Therefore,
      fluorescence labeling of CNTs with various probes under physiological conditions
      has become a significant issue for their utilization in biological processes.
      Herein, we demonstrate a facile and additional fluorophore-free approach for
      cancer cell-imaging and diagnosis by combining multiwalled CNTs with a well-known
      conjugated polymer, namely, poly(p-phenylene) (PP). In this approach, PP
      decorated with poly(ethylene glycol) (PEG) was noncovalently (pi-pi stacking)
      linked to acid-treated CNTs. The obtained water self-dispersible, stable, and
      biocompatible f-CNT/PP-g-PEG conjugates were then bioconjugated to estrogen
      specific antibody (anti-ER) via -COOH functionalities present on the side-walls
      of CNTs. The resulting conjugates were used as an efficient fluorescent probe for
      targeted imaging of estrogen receptor overexpressed cancer cells, such as MCF-7.
      In vitro studies and fluorescence microscopy data show that these conjugates can
      specifically bind to MCF-7 cells with high efficiency. The represented results
      imply that CNT-based materials could easily be fabricated by the described
      approach and used as an efficient "fluorescent probe" for targeting and imaging,
      thereby providing many new possibilities for various applications in biomedical
      sensing and diagnosis.

PMID- 22866989
TI  - Urology resident experience with an elective in interventional radiology: a pilot
      evaluation.
AB  - PURPOSE: The objective of the study was to evaluate the initial experience with
      an elective in interventional uroradiology. METHODS: Seven urology residents
      completed a minimum 2-month elective in interventional radiology (IR). A survey
      was administered before and immediately after the elective. The survey sought
      information on proficiency in uroradiology procedures and the role of IR in
      current training and future practice based on a 5-point ascending Likert response
      scale. Procedures performed during the elective were reviewed and recorded from
      the resident case logs. RESULTS: Urology residents reported an increased
      proficiency in all interventional procedures after the IR rotation. Endovascular
      techniques, ablative therapies, and needle biopsy had significant increases in
      performance proficiency (P=0.031). On completion, residents strongly agreed that
      interventional uroradiology should be a part of residency training, and image
      guided therapies will play a significant role in the future of urology. Residents
      performed on average 14.9 arterial interventions, 28.5 venous interventions, 15.8
      genitourinary interventions, and 3.1 tumor ablations per month. In addition,
      urology residents performed image-guided biopsies, drainages, as well as
      gastrointestinal and biliary interventions gaining experience with performing and
      interpreting ultrasonography, fluoroscopy, and CT. CONCLUSION: Interventional
      uroradiology provides urology residents invaluable experience with image-guided
      procedures, increasing comfort with performance and interpretation. Residents
      believed that interventional uroradiology should be incorporated into the
      residency curriculum.

PMID- 22866990
TI  - Effectiveness of an e-learning curriculum on occupational health for music
      performers.
AB  - OBJECTIVE: The purpose of this study was (1) to evaluate the effectiveness of the
      e-learning curriculum and (2) to explore the type of questions raised by students
      through the "Health Promotion for Music Performers" (HPMP) e-learning curriculum.
      MATERIALS AND METHODS: This study was primarily a pedagogical research composed
      of a pre- and postintervention design coupled with a 1-month longitudinal
      knowledge retention measurement. The intervention, the HPMP e-learning
      curriculum, was implemented over 14 weeks, once a week, for a total of 14
      classes. Each class consisted of a 60-min prerecorded lecture followed by a 40
      min real-time interactive discussion. The interdisciplinary faculty panel
      consisted of experts from the field of music and medicine. The Self-Assessment
      Questionnaire (SAQ) was used to evaluate knowledge changes concerning (1)
      Practice and Performance issues and (2) Health and Life Style issues. RESULTS:
      Fifteen graduate-level music students participated in the study. The SAQ scores
      on the 1-month follow-up test for Practice and Performance issues were
      significantly higher than the pretest (t=2.731, p<0.05). On the other hand, no
      significant differences were found between the posttest and pretest or between
      the follow-up test and posttest. Regarding Health and Life Style issues,
      comparison at all three measurement points did not reveal any significant
      difference. Questions raised by students fell into four major categories:
      performance injury (45%), performance anxiety (22%), general physiology (22%),
      and general psychology (11%). CONCLUSIONS: The findings suggest that the HPMP e
      learning course enhanced student awareness of Practice and Performance issues but
      did not have as significant an impact on student awareness of Health and
      Lifestyle issues.

PMID- 22866991
TI  - In the absence of thioredoxins, what are the reductants for peroxiredoxins in
      Thermotoga maritima?
AB  - Three peroxiredoxins (Prxs) were identified in Thermotoga maritima, which
      possesses neither glutathione nor typical thioredoxins: one of the Prx6 class;
      one 2-Cys PrxBCP; and a unique hybrid protein containing an N-terminal 1-Cys
      PrxBCP domain fused to a flavin mononucleotide-containing nitroreductase (Ntr)
      domain. No peroxidase activity was detected for Prx6, whereas both
      bacterioferritin comigratory proteins (BCPs) were regenerated by a
      NADH/thioredoxin reductase/glutaredoxin (Grx)-like system, constituting a unique
      peroxide removal system. Only two of the three Grx-like proteins were able to
      support peroxidase activity. The inability of TmGrx1 to regenerate oxidized 2-Cys
      PrxBCP probably results from the thermodynamically unfavorable difference in
      their disulfide/dithiol E(m) values, -150 and -315 mV, respectively. Mutagenesis
      of the Prx-Ntr fusion, combined with kinetic and structural analyses, indicated
      that electrons are not transferred between its two domains. However, their
      separate activities could function in a complementary manner, with peroxide
      originating from the chromate reductase activity of the Ntr domain reduced by the
      Prx domain.

PMID- 22866992
TI  - Photoluminescence enhancement of quantum dots on Ag nanoneedles.
AB  - Noble metal nanostructure allows us to tune optical and electrical properties,
      which has high utility for real-world application. We studied surface plasmon
      induced emission of semiconductor quantum dots (QDs) on engineered metallic
      nanostructures. Highly passive organic ZnS-capped CdSe QDs were spin-coated on
      poly-(methyl methacrylate)-covered Ag films, which brought QDs near the metallic
      surface. We obtained the enhanced electromagnetic field and reduced fluorescence
      lifetimes from CdSe/ZnS QDs due to the strong coupling of emitter wave function
      with the Ag plasmon resonance. Observed changes include a six-fold increase in
      the fluorescence intensity and striking reduction in fluorescence lifetimes of
      CdSe/ZnS QDs on rough Ag nanoneedle compared to the case of smooth surfaces. The
      advantages of using those nanocomposites are expected for high-efficiency light
      emitting diodes, platform fabrication of biological and environmental monitoring,
      and high-contrast imaging.

PMID- 22866993
TI  - Determination of polyphenols in Spanish wines by capillary zone electrophoresis.
      Application to wine characterization by using chemometrics.
AB  - A capillary zone electrophoresis (CZE) method for the simultaneous determination
      of 20 polyphenols in wine was developed. The separation was performed using fused
      silica capillaries of 75 MUm i.d. and a 30 mM sodium tretraborate buffer solution
      at pH 9.2 with 5% isopropanol as a background electrolyte. A capillary voltage of
      +25 kV with pressure-assisted (3.5 kPa) separation from minute 18 was applied,
      thus achieving a total analysis time of <25 min. Instrumental quality parameters
      such as limits of detection (LOD, values between 0.3 and 2.6 mg/L), linearity
      (r(2) > 0.990), and run-to-run and day-to-day precisions (RSD values lower than
      6.5 and 15.7%, respectively) were established. Three different calibration
      procedures were evaluated for polyphenol quantitation in wines: external
      calibration using standards prepared in Milli-Q water, standard addition, and
      pseudomatrix-matched calibration using wine as a matrix. For a 95% confidence
      level, no statistical differences were observed, in general, between the three
      calibration methods (p values between 0.11 and 0.84), whereas for some specific
      polyphenols, such as cinnamic acid, syringic acid, and gallic acid, results were
      not comparable when external calibration was used. The CZE method using
      pseudomatrix-matched calibration was then proposed and applied to the analysis of
      polyphenols in 49 Spanish wines, showing satisfactory results and a wide
      compositional variation between wines. Electrophoretic profiles and other
      compositional data (e.g., peak areas of selected peaks) were considered as
      fingerprints of wines to be used for characterization and classification
      purposes. The corresponding data were analyzed by principal component analysis
      (PCA) to extract information on the most significant features contributing to
      wine discrimination according to their origins. Results showed that a reasonable
      distribution of wines depending on the elaboration areas was found, tyrosol and
      gallic, protocatechuic, p-coumaric, and caffeic acids being some representative
      discriminant compounds. 

PMID- 22866995
TI  - Knee injuries in severe trauma patients: a trauma registry study in 3.458
      patients.
AB  - BACKGROUND: Purpose of the presented study is to answer the following questions:
      Are knee injuries associated with trauma mechanisms or concomitant injuries? Do
      injuries of the knee region aggravate treatment costs or prolong hospital stay in
      polytraumatized patients? METHODS: A retrospective analysis including 29.779
      severely injured patients (Injury Severity Score [greater than or equal to] 16)
      from the Trauma Registry of the German Society for Trauma Surgery database (1993
      2008) was conducted. Patients were subdivided into two groups; the "Knee" group
      (n=3.458, 11.6% of all patients) including all multiple trauma patients with knee
      injuries, and the "Non Knee" group (n=26.321) including the remaining patients.
      Patients with knee injuries were slightly younger, less often male gender and had
      a significantly increased ISS. RESULTS: Patients in the Knee group suffered
      significantly more traffic accidents compared to the Non Knee group (82% vs. 52%,
      p<0.001). These injuries were more often caused by car or motorbike accidents.
      Severe thoracic and limb injuries (AIS[greater than or equal to]3) were more
      frequently found in the Knee group (p<0.001) while head injury was distributed
      equally. The overall hospital stay, ICU stay, and treatment costs were
      significantly higher for the Knee group (38.1 vs. 25.5 days, 15.2 vs. 11.4 days,
      40,116 vs. 25,336 Euro, respectively; all p<0.001). CONCLUSIONS: Traffic
      accidents are associated with an increased incidence of knee injuries than falls
      or attempted suicides. Furthermore, severe injuries of the limbs and chest are
      more common in polytraumatized patients with knee injuries. At last, treatment of
      these patients is prolonged and consequently more expensive.

PMID- 22866996
TI  - Yoga Nidra relaxation increases heart rate variability and is unaffected by a
      prior bout of Hatha yoga.
AB  - OBJECTIVE: The measurement of heart rate variability (HRV) is often applied as an
      index of autonomic nervous system (ANS) balance and, therefore, myocardial
      stability. Previous studies have suggested that relaxation or mind-body exercise
      can influence ANS balance positively as measured by HRV but may act via different
      mechanisms. No studies, to the authors' knowledge, have examined the acute
      response in HRV to interventions combining relaxation and mind-body exercise. The
      objective of this study was to compare the acute HRV responses to Yoga Nidra
      relaxation alone versus Yoga Nidra relaxation preceded by Hatha yoga. DESIGN:
      This was a randomized counter-balanced trial. SETTING: The trial was conducted in
      a university exercise physiology laboratory. SUBJECTS: Subjects included 20 women
      and men (29.15+/-6.98 years of age, with a range of 18-47 years). INTERVENTIONS:
      Participants completed a yoga plus relaxation (YR) session and a relaxation only
      (R) session. RESULTS: The YR condition produced significant changes from baseline
      in heart rate (HR; beats per minute [bpm], p<0.001) and indices of HRV: R-R (ms,
      p<0.001), pNN50 (%, p=0.009), low frequency (LF; %, p=0.008) and high frequency
      (HF; %, p=0.035). The R condition produced significant changes from baseline in
      heart rate (bpm, p<0.001) as well as indices of HRV: R-R (ms, p<0.001), HF
      (ms(2), p=0.004), LF (%, p=0.005), HF (%, p=0.008) and LF:HF ratio (%, p=0.008).
      There were no significant differences between conditions at baseline nor for the
      changes from baseline for any of the variables. CONCLUSIONS: These changes
      demonstrate a favorable shift in autonomic balance to the parasympathetic branch
      of the ANS for both conditions, and that Yoga Nidra relaxation produces favorable
      changes in measures of HRV whether alone or preceded by a bout of Hatha yoga.

PMID- 22866997
TI  - Clinical and microbiological characterization of Staphylococcus lugdunensis
      isolates obtained from clinical specimens in a hospital in China.
AB  - BACKGROUND: Several reports have associated Staphylococcus lugdunensis with the
      incidence of severe infection in humans; however, the frequency and prevalence of
      this microorganism and thus the propensity of its antimicrobial drug resistance
      is unknown in China. The objective of the current study was to determine the
      prevalence of Staphylococcus lugdunensis among six hundred and seventy non
      replicate coagulase negative Staphylococcus (CoNS) isolates collected in a 12
      month period from clinical specimens in the General Hospital of the People's
      Liberation Army in Beijing, China. RESULTS: Five (0.7%) of the 670 isolates of
      CoNS were identified as S. lugdunensis. Whereas three isolates were resistant to
      erythromycin, clindamycin, and penicillin and carried the ermC gene and a fourth
      one was resistant to cefoxitin and penicillin and carried the mecA gene, one
      isolate was not resistant to any of the tested antimicrobials. Pulse field gel
      electrophoretic analysis did not reveal widespread epidemiological diversity of
      the different isolates. CONCLUSION: Hence, even though S. lugdunensis may be yet
      unrecognized and undefined in China, it still might be the infrequent cause of
      infection and profound multi-drug resistance in the same population.

PMID- 22866999
TI  - The Barcelona Declaration from the World Alliance against Antibiotic Resistance:
      engagement of intensivists.

PMID- 22866998
TI  - Parents as agents of change (PAC) in pediatric weight management: the protocol
      for the PAC randomized clinical trial.
AB  - BACKGROUND: There is an urgent need to develop and evaluate weight management
      interventions to address childhood obesity. Recent research suggests that
      interventions designed for parents exclusively, which have been named parents as
      agents of change (PAC) approaches, have yielded positive outcomes for managing
      pediatric obesity. To date, no research has combined a PAC intervention approach
      with cognitive behavioural therapy (CBT) to examine whether these combined
      elements enhance intervention effectiveness. This paper describes the protocol
      our team is using to examine two PAC-based interventions for pediatric weight
      management. We hypothesize that children with obesity whose parents complete a
      CBT-based PAC intervention will achieve greater reductions in adiposity and
      improvements in cardiometabolic risk factors, lifestyle behaviours, and
      psychosocial outcomes than children whose parents complete a psycho-education
      based PAC intervention (PEP). METHODS/DESIGN: This study is a pragmatic, two
      armed, parallel, single-blinded, superiority, randomized clinical trial. The
      primary objective is to examine the differential effects of a CBT-based PAC vs
      PEP-based PAC intervention on children's BMI z-score (primary outcome). Secondary
      objectives are to assess intervention-mediated changes in cardiometabolic,
      lifestyle, and psychosocial variables in children and parents. Both interventions
      are similar in frequency of contact, session duration, group facilitation,
      lifestyle behaviour goals, and educational content. However, the interventions
      differ insofar as the CBT-based intervention incorporates theory-based concepts
      to help parents link their thoughts, feelings, and behaviours; these cognitive
      activities are enabled by group leaders who possess formal training in CBT.
      Mothers and fathers of children (8-12 years of age; BMI >=85th percentile) are
      eligible to participate if they are proficient in English (written and spoken)
      and agree for at least one parent to attend group-based sessions on a weekly
      basis. Anthropometry, cardiometabolic risk factors, lifestyle behaviours, and
      psychosocial health of children and parents are assessed at pre-intervention,
      post-intervention, 6-, and 12-months follow-up. DISCUSSION: This study is
      designed to extend findings from earlier efficacy studies and provide data on the
      effect of a CBT-based PAC intervention for managing pediatric obesity in a real
      world, outpatient clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT01267097.

PMID- 22867000
TI  - China's regional inequity in pharmacist's drug safety practice.
AB  - BACKGROUND: The promotion of patient safety and drug safety through promotion of
      pharmacist's drug safety practice was among the most important aims of China's
      health delivery system reform, but regional inequity in pharmacist's drug safety
      practice was still serious in China. METHODS: The 2011 national patient safety
      and medication error baseline survey was carried out for the first time in China,
      and through analyzing dataset from the survey, this study was set up to test both
      China's regional inequity in pharmacist's drug safety practice and major
      influencing factors for pharmacist's drug safety practice among different
      districts of China. RESULTS: Pharmacist's drug safety practice in regions with
      higher per capita GDP and more abundant medical resources was still better than
      that in regions with lower per capita GDP and less abundant medical resources. In
      all districts of China, pharmacist's drug safety knowledge, drug safety attitude,
      self-perceived pressure and fatigue, hospital management quality, and hospital
      regulation were major influencing factors for pharmacist's drug safety practice,
      while only in regions with higher per capita GDP and more abundant medical
      resources, hospital drug safety culture, supervisor's work team management,
      cooperation atmosphere of work team, and drug safety culture of work team were
      major influencing factors for pharmacist's drug safety practice. CONCLUSION:
      Regional inequity in pharmacist's drug safety practice still existed in China. In
      all districts of China, promoting pharmacist's drug safety knowledge, drug safety
      attitude, self-perceived pressure and fatigue, hospital management quality, and
      hospital regulation could help promote pharmacist's drug safety practice, while
      only in regions with higher per capita GDP and more abundant medical resources,
      promoting hospital drug safety culture, supervisor's work team management,
      cooperation atmosphere of work team, and drug safety culture of work team could
      help promote pharmacist's drug safety practice. And in regions with lower per
      capita GDP and less abundant medical resources, the link between pharmacist's
      drug safety practice and hospital drug safety culture/supervisor's work team
      management/cooperation atmosphere of work team/drug safety culture of work team
      should also be gradually established.

PMID- 22867001
TI  - Design, synthesis, and evaluation of pH-dependent hydrolyzable emetine analogues
      as treatment for prostate cancer.
AB  - The N-2' position of the natural product emetine has been derivatized to
      thiourea, urea, sulfonamide, dithiocarbamate, carbamate, and pH responsive
      hydrolyzable amide analogues. In vitro studies of these analogues in PC3 and
      LNCaP prostate cancer cell lines showed that the analogues are generally less
      cytotoxic (average IC(50) ranging from 0.079 to 10 MUM) than emetine (IC(50)
      ranging from 0.0237 to 0.0329 MUM). The pH sensitive sodium dithiocarbamate salt
      13 and the amide analogues 21, 22, 26 (obtained from maleic and citraconic
      anhydrides) showed the most promise as acid-activatable prodrugs under mildly
      acidic conditions found in the cancer microenvironment. These prodrugs released
      12-83% of emetine at pH 6.5 and 41-95% emetine at pH 5.5. Compounds 13 and 26
      were further shown to exhibit increased cytotoxicity in PC3 cell culture medium
      that was already below pH 7.0 at the time of treatment.

PMID- 22867002
TI  - Substituent effects on the electronic characteristics of pentacene derivatives
      for organic electronic devices: dioxolane-substituted pentacene derivatives with
      triisopropylsilylethynyl functional groups.
AB  - The intramolecular electronic structures and intermolecular electronic
      interactions of 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene),
      6,14-bis-(triisopropylsilylethynyl)-1,3,9,11-tetraoxa-dicyclopenta[b,m]-pentacene
      (TP-5 pentacene), and 2,2,10,10-tetraethyl-6,14-bis-(triisopropylsilylethynyl)
      1,3,9,11-tetraoxa-dicyclopenta[b,m]pentacene (EtTP-5 pentacene) have been
      investigated by the combination of gas-phase and solid-phase photoelectron
      spectroscopy measurements. Further insight has been provided by electrochemical
      measurements in solution, and the principles that emerge are supported by
      electronic structure calculations. The measurements show that the energies of
      electron transfer such as the reorganization energies, ionization energies,
      charge-injection barriers, polarization energies, and HOMO-LUMO energy gaps are
      strongly dependent on the particular functionalization of the pentacene core. The
      ionization energy trends as a function of the substitution observed for molecules
      in the gas phase are not reproduced in measurements of the molecules in the
      condensed phase due to polarization effects in the solid. The electronic behavior
      of these materials is impacted less by the direct substituent electronic effects
      on the individual molecules than by the indirect consequences of substituent
      effects on the intermolecular interactions. The ionization energies as a function
      of film thickness give information on the relative electrical conductivity of the
      films, and all three molecules show different material behavior. The stronger
      intermolecular interactions in TP-5 pentacene films lead to better charge
      transfer properties versus those in TIPS pentacene films, and EtTP-5 pentacene
      films have very weak intermolecular interactions and the poorest charge transfer
      properties of these molecules.

PMID- 22867003
TI  - Airport sentinel surveillance and entry quarantine for dengue infections
      following a fever screening program in Taiwan.
AB  - BACKGROUND: Dengue has not reached an endemic status in Taiwan; nevertheless, we
      have implemented a fever screening program at airports for the early detection of
      febrile passengers with a dengue infection. This study is intended to assess the
      performance of the airport screening procedures for dengue infection. METHODS: We
      analyzed data from the national surveillance system of the Taiwan Centers for
      Disease Control. We included the imported dengue cases reported by sentinel
      airports and clinics as well as the domestic cases from 2007-2010. RESULTS:
      Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases
      with an apparent symptom (febrile) in the viremic stage were detected via the
      airport fever screening program, with an estimated positive predictive value of
      2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%.
      Fluctuations in the number of the symptomatic imported dengue cases identified in
      the airports (X) were associated with the total number of imported dengue cases
      (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104,
      R(2)(X:Y) = 0.61, P < 0.005). Additionally, the fluctuating patterns in the
      cumulative numbers of the imported dengue cases (X) with a 1-2 month lead time
      (t) was in parallel with that of the domestic dengue cases (Y) based on a
      consecutive 4-year surveillance (i.e., n = 48, R(2)(X(t-1):Y) = 0.22, R(2)(X(t
      2):Y) = 0.31, P < 0.001) from 2007-2010. CONCLUSIONS: A moderate sensitivity of
      detecting dengue at the airports examined in this study indicated some
      limitations of the fever screening program for the prevention of importation. The
      screening program could assist in the rapid triage for self-quarantine of some
      symptomatic dengue cases that were in the viremic stage at the borders and
      contribute to active sentinel surveillance; however, the blocking of viral
      transmission to susceptible populations (neighbors or family) from all of the
      viremic travelers, including those with or without symptoms, is critical to
      prevent dengue epidemics. Therefore, the reinforcement of mosquito bite
      prevention and household vector control in dengue-endemic or dengue-competent
      hotspots during an epidemic season is essential and highly recommended.

PMID- 22867004
TI  - Is a self-rated instrument appropriate to assess mentalization in patients with
      mental disorders? Development and first validation of the mentalization
      questionnaire (MZQ).
AB  - The purpose of this study was to develop and validate a self-rating scale for a
      differentiated assessment of mentalization. A pool of 40 items was developed and
      evaluated on n=434 inpatients with mental disorders at three time points. Symptom
      severity, self-injuring behavior, suicidal tendency and attachment style were
      also assessed. A varimax-rotated factor analysis supported the extraction of four
      factors. The model fit was checked by confirmatory factor analysis. Internal
      consistency of the mentalization questionnaire (MZQ) was .81. The relation
      between symptom severity and MZQ scores was found to be significant, and
      significant group differences were found between patients displaying self
      injuring behavior and those who did not as well as between patients with and
      without suicide attempts. The MZQ can be considered as a practicable self-rated
      instrument with acceptable reliability and sufficient validity to assess at least
      aspects of mentalization in patients with mental disorders.

PMID- 22867005
TI  - A qualitative exploration of the role of social networks in educating urban
      African American adolescents about sex.
AB  - OBJECTIVE: To explore social network members' role in educating African American
      adolescents about sexual health issues. DESIGN: We conducted 21 focus groups with
      urban African American mothers (n=51), fathers (n=18), sons (n=20), and daughters
      (n=36) from Allegheny County, Pennsylvania, USA, between December 2007 and March
      2008. At least one biological parent (or legal guardian) and one adolescent aged
      15-17 years from each family participated. Group conversations were audio
      recorded, transcribed, and analyzed using directive content analysis and the
      constant comparison method. Two coders independently read each transcript to
      identify emergent themes. RESULTS: A broad range of people were reportedly
      involved in the education process. Older siblings, extended family, and peers
      were most commonly cited. However, unrelated adults were also described as
      playing important roles. Unrelated adults included the friends of an adolescent's
      parents and the parents of an adolescent's friends or romantic partners. Social
      network members were said to address three main issues: the facts about sex and
      sexuality, the social aspects of sexuality (e.g., appropriate dating behaviors,
      choosing dating partners), and promotion of family values. When educating
      adolescents about sex, social network members were described as playing eight
      functional roles, including that of a teacher, guide, challenger, confidant,
      shelterer, supervisor-chaperone, role model, and provider of access to
      reproductive health services. These roles were not mutually exclusive, meaning
      that social network members often assumed different roles depending on the
      situation. The influence of individuals who were not an adolescent's parent was
      highly dependent on adolescents' relationship with their parents or on their
      parents' comfort dealing with sexual issues. CONCLUSIONS: African American
      adolescents' social networks were described by parents and adolescents as dense,
      complex, and routinely involved in educating adolescents about sex.

PMID- 22867006
TI  - Norbornene-derived poly-D-lysine copolymers as quantum dot carriers for neuron
      growth.
AB  - Synthesis of norbornene derived phosphonate (1), poly-D-lysine (2), and
      phopholipid (3) monomers and their complete characterizations are studied. Ring
      opening metathesis polymerizations (ROMP) of monomers (1-3) produce well-defined
      copolymers, CP(1) and CP(2). (1)H NMR along with FT-IR spectroscopy
      characterization confirms the copolymer formation, while gel permeation
      chromatography (GPC) analysis suggests the formation of polymers with fairly
      narrow molecular weight distributions. Upon following the well-known ligand
      exchange methods these copolymers produce CdSe-bound copolymers, CP(3) and CP(4).
      Dynamic light scattering and transmission electron microscopy measures the size
      of these CdSe bound copolymers, while (31)P NMR suggests the formation of CP(3)
      and CP(4). The results from the experiments of these copolymers on Neuro2A cells
      suggest that the novel PDL-anchored nanomaterial show their ability to polarize
      neuronal growth and differentiation.

PMID- 22867007
TI  - Postharvest polyamine application alleviates chilling injury and affects apricot
      storage ability.
AB  - Fruit of two apricot cultivars 'Bagheri' and 'Asgarabadi' were treated with
      putrescine (Put) or spermidine (Spd) at 1 mM and then were stored at 1  degrees C
      for 21 days. Fruit were sampled weekly and stored 2 days at 20  degrees C for
      shelf-life study. The treatments reduced ethylene production and maintained the
      firmness and color of the fruit. Peroxidase (POX), catalase (CAT), superoxide
      dismutase (SOD), and polyphenol oxidase (PPO) activities and total phenol (TP)
      concentrations were measured during storage. Both cultivars showed chilling
      injury (CI) incidence, and the severity in control fruit was higher than either
      Put or Spd treatments. CI incidence in Spd-treated fruit was lower than that of
      Put-treated fruit. Polyamine (PA) treatment generally increased antioxidant
      enzyme activity of fruit during storage. PA treatments may help maintain the
      quality of apricot fruit during storage by inhibiting ripening and decreasing CI
      incidence.

PMID- 22867008
TI  - Greater numbers of nucleotide substitutions are introduced into the genomic RNA
      of bovine viral diarrhea virus during acute infections of pregnant cattle than of
      non-pregnant cattle.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) strains circulating in livestock
      herds show significant sequence variation. Conventional wisdom states that most
      sequence variation arises during acute infections in response to immune or other
      environmental pressures. A recent study showed that more nucleotide changes were
      introduced into the BVDV genomic RNA during the establishment of a single fetal
      persistent infection than following a series of acute infections of naive cattle.
      However, it was not known if nucleotide changes were introduce when the virus
      crossed the placenta and infected the fetus or during the acute infection of the
      dam. METHODS: The sequence of the open reading frame (ORF) from viruses isolated
      from four acutely infected pregnant heifers following exposure to persistently
      infected (PI) calves was compared to the sequences of the virus from the
      progenitor PI calf and the virus from the resulting progeny PI calf to determine
      when genetic change was introduced. This was compared to genetic change found in
      viruses isolated from a pregnant PI cow and its PI calf, and in three viruses
      isolated from acutely infected, non-pregnant cattle exposed to PI calves.
      RESULTS: Most genetic changes previously identified between the progenitor and
      progeny PI viruses were in place in the acute phase viruses isolated from the
      dams six days post-exposure to the progenitor PI calf. Additionally, each progeny
      PI virus had two to three unique nucleotide substitutions that were introduced in
      crossing the placenta and infection of the fetus. The nucleotide sequence of two
      acute phase viruses isolated from steers exposed to PI calves revealed that six
      and seven nucleotide changes were introduced during the acute infection. The
      sequence of the BVDV-2 virus isolated from an acute infection of a PI calf (BVDV
      1a) co-housed with a BVDV-2 PI calf had ten nucleotides that were different from
      the progenitor PI virus. Finally, twenty nucleotide changes were identified in
      the PI virus of a calf born to a PI dam. CONCLUSIONS: These results demonstrate
      that nucleotide changes are introduced into the BVDV infecting pregnant cattle at
      rates of 2.3 to 8 fold higher then during the acute infection of non-pregnant
      animals.

PMID- 22867009
TI  - A generalizability analysis of score consistency for the Balanced Inventory of
      Desirable Responding.
AB  - Our goal in this investigation was to evaluate the reliability of scores from the
      Balanced Inventory of Desirable Responding (BIDR) more comprehensively than in
      prior research using a generalizability-theory framework based on both
      dichotomous and polytomous scoring of items. Generalizability coefficients
      accounting for specific-factor, transient, and random-response error ranged from
      .64 to .75 for the BIDR's Self-Deception Enhancement (SDE) and Impression
      Management (IM) subscale scores, and these values were systematically lower than
      corresponding alpha (.66 to .83) and 1-week test-retest (.78 to .86)
      coefficients. Polytomous scoring provided higher reliability than dichotomous
      scoring on nearly all indexes reported. Random-response (8%-17%) and specific
      factor error (11%-17%) exceeded transient error (3%-6%) for both subscales and
      scoring methods. Doubling the number of items on a single occasion provided
      greater improvements in generalizability (.76-.83) than aggregating scores across
      2 administrations (.72-.81). Both scoring methods provided reasonably high
      indexes of consistency (phi coefficients>=.91) at cut scores on the IM scale for
      detecting faked responses when all sources of error were taken into account.
      Implications of these results for common uses of the BIDR are discussed.

PMID- 22867010
TI  - The Child PTSD Symptom Scale: psychometric properties in female adolescent sexual
      assault survivors.
AB  - Traumatic experiences are common among youths and can lead to posttraumatic
      stress disorder (PTSD). In order to identify traumatized children who need PTSD
      treatment, instruments that can accurately and efficiently evaluate pediatric
      PTSD are needed. One such measure is the Child PTSD Symptom Scale (CPSS), which
      has been found to be a reliable and valid measure of PTSD symptom severity in
      school-age children exposed to natural disasters (Foa, Johnson, Feeny, &
      Treadwell, 2001). However, the psychometric properties of the CPSS are not known
      in youths who have experienced other types of trauma. The current study aims to
      fill this gap by examining the psychometric properties of the interview (CPSS-I)
      and self-report (CPSS-SR) administrations of the CPSS in a sample of 91 female
      youths with sexual abuse-related PTSD, a population that is targeted in many
      treatment studies. Scores on both the CPSS-I and CPSS-SR demonstrated good to
      excellent internal consistency. One-week test-retest reliability assessed for
      CPSS-SR scores was excellent (r=.86); interrater reliability of CPSS-I scores was
      also excellent (r=.87). Symptom-based diagnostic agreement between the CPSS-SR
      and CPSS-I was excellent at 85.5%; scores on both the CPSS-SR and CPSS-I also
      demonstrated good convergent validity (74.5-76.5% agreement) with the PTSD module
      of The Schedule of Affective Disorders and Schizophrenia for School-Age Children-
      Revised for DSM--IV (K-SADS; Kaufman, Birmaher, Brent, & Rao, 1997). The strong
      psychometric properties of the CPSS render it a valuable instrument for PTSD
      screening as well as for assessing symptom severity.

PMID- 22867011
TI  - The SRP-II as a rich source of data on the psychopathic personality.
AB  - This study examined the factor structure, external correlates, and predictive
      utility of the Self-Report Psychopathy scale (SRP-II; Hare, Harpur, & Hemphill,
      1989). Despite a revision of the SRP-II to address, among other criticisms, a
      lack of items reflecting antisocial behavior, we hypothesized that the SRP-II
      would have a conceptually coherent factor structure and sufficiently tap facets
      of the psychopathic personality. Participants for the present investigation were
      1,257 undergraduate students who completed a battery of psychological tests.
      Confirmatory factor analyses of previous 2-factor models did not fit the data
      well. A series of exploratory and confirmatory factor analyses revealed a
      rationally derived 4-factor model to have the best fit. This model was
      conceptually coherent, and the factors were linked to, and significant predictors
      of, external correlates relevant to psychopathy. Indeed, the present study
      suggests that the SRP-II provides a rich source of data for examining the
      construct of psychopathy as delineated by Cleckley (1941), while also tapping the
      personality-oriented facets of Hare's 4-factor model.

PMID- 22867012
TI  - Neuron-specific enolase, but not S100B or myelin basic protein, increases in
      peripheral blood corresponding to lesion volume after cortical impact in piglets.
AB  - A peripheral indicator of the presence and magnitude of brain injury has been a
      sought-after tool by clinicians. We measured neuron-specific enolase (NSE),
      myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact
      in immature pigs, to determine if these purported markers increase after injury,
      correlate with the resulting lesion volume, and if these relationships vary with
      maturation. Scaled cortical impact resulted in increased lesion volume with
      increasing age. Concentrations of NSE, but not S100B or MBP, increased after
      injury in all age groups. The high variability of S100B concentrations prior to
      injury may have precluded detection of an increase due to injury. Total serum
      markers were estimated, accounting for the allometric growth of blood volume, and
      resulted in a positive correlation of both NSE and S100B with lesion volume. Even
      with allometric scaling of blood volume and a uniform mechanism of injury, NSE
      had only a fair to poor predictive value. In a clinical setting, where the types
      of injuries are varied, more investigation is required to yield a panel of serum
      markers that can reliably predict the extent of injury. Allometric scaling may
      improve estimation of serum marker release in pediatric populations.

PMID- 22867013
TI  - Cyclization strategies to polyenes using Pd(II)-catalyzed couplings of pinacol
      vinylboronates.
AB  - As a complement to Pd(0)-catalyzed cyclizations, seven Pd(II)-catalyzed
      cyclization strategies are reported. alpha,omega-Diynes are selectively
      hydroborated to bis(boronate esters), which cyclize under Pd(II)-catalysis
      producing a diverse array of small, medium, and macrocyclic polyenes with
      controlled E,E, Z,Z, or E,Z stereochemistry. Various functional groups are
      tolerated including aryl bromides, and applications are illustrated.

PMID- 22867014
TI  - Late decompressive craniectomyafter traumatic brain injury: neurological outcome
      at 6 months after ICU discharge.
AB  - INTRODUCTION: The choice of optimal treatment in traumatic brain injured (TBI)
      patients is a challenge. The aim of this study was to verify the neurological
      outcome of severe TBI patients treated with decompressive craniectomy (early < 24
      h, late > 24 h), compared to conservative treatment, in hospital and after 6
      months. METHODS: A total of 186 TBI patients admitted to the ICU of the Emergency
      Department of a tertiary referral center (Careggi Teaching Hospital, Florence,
      Italy) from 2005 through 2009 were retrospectively studied. Patients treated with
      decompressive craniectomy were divided into 2 groups: "early craniectomy group"
      (patients who underwent to craniectomy within the first 24 hours); and "late
      craniectomy group" (patients who underwent to craniectomy later than the first 24
      hours). As a control group, patients whose intracranial hypertension was
      successfully controlled by medical treatment were included in the "no craniectomy
      group". RESULTS: Groups included 41 patients who required early decompressive
      craniectomy, 21 patients treated with late craniectomy (7.7 days after trauma, on
      average), and 124 patients for whom intracranial hypertension was successfully
      controlled through conservative treatment. Groups were comparable in age and
      trauma/critical illness scores, except for a significantly higher Marshall score
      in early craniectomized patients. The Glasgow Outcome Scale was comparable
      between groups at ICU, at the time of hospital discharge and at 6 months.
      CONCLUSIONS: In our sample, a late craniectomy in patients with refractory
      intracranial hypertension produced a comparable 6-months neurological outcome if
      compared to patients responder to standard treatment. This data must be
      reproduced and confirmed before considering as goal-treatment in refractory
      intracranial hypertension.

PMID- 22867015
TI  - Do kinaesthetic tapes affect plantarflexor muscle performance?
AB  - This study aimed to examine the effects of application of kinaesthetic tapes on
      plantarflexor muscle performance. We hypothesised that taping of the triceps
      surae muscle would improve plantarflexor muscle strength and endurance with no
      significant effect on drop jump performance. Using a repeated-measures design,
      all performance measures were obtained in 24 volunteers on two separate
      occasions: without tapes and after application of kinaesthetic tapes. Performance
      tests included measurements of isometric plantarflexor muscle strength and the
      associated electromyographic activity of the gastrocnemius muscle, an isokinetic
      fatigue resistance test (30 contractions at 180 degrees  . s(-1)) and assessments
      of drop jump performance. The taping-intervention was associated with an increase
      in gastrocnemius electromyographic activity. However, significant increases in
      isometric strength were only found at fully dorsiflexed ankle positions (+12% at 
      20 degrees ). Strength gains were negatively correlated to baseline strength (r =
      -.58). The intervention did not affect the results of the isokinetic fatigue and
      drop jump tests. The application of kinaesthetic tapes over the triceps surae
      muscle promotes an increase in isometric strength and gastrocnemius muscle
      activity. Our data suggest that these effects are joint-angle dependent and more
      prominent in weaker individuals. By contrast, the taping-intervention improves
      neither drop jump performance nor muscular endurance.

PMID- 22867016
TI  - Pyridinylidene-phenoxide in strong electric fields: controlling orientation,
      conical intersection, and radiation-less decay.
AB  - Strong electric fields open new routes for the control of radiation-less decay in
      molecules with conical intersections. Here, we present quantum chemical and
      quantum dynamical simulations which demonstrate that the radiation-less decay and
      related photoisomerization of pyridinylidene-phenoxide can be effectively
      manipulated with strong electric fields by shifting the conical intersection.
      Moreover, we show the effects of the electric field on the orientation of the
      molecules and on the photoexcitation and discuss the conditions for which the
      field induced coupling between rotational and vibronic states can be neglected.

PMID- 22867018
TI  - Relationships between kinetic constants and the amino acid composition of enzymes
      from the yeast Saccharomyces cerevisiae glycolysis pathway.
AB  - The kinetic models of metabolic pathways represent a system of biochemical
      reactions in terms of metabolic fluxes and enzyme kinetics. Therefore, the
      apparent differences of metabolic fluxes might reflect distinctive kinetic
      characteristics, as well as sequence-dependent properties of the employed
      enzymes. This study aims to examine possible linkages between kinetic constants
      and the amino acid (AA) composition (AAC) for enzymes from the yeast
      Saccharomyces cerevisiae glycolytic pathway. The values of Michaelis-Menten
      constant (KM), turnover number (kcat), and specificity constant (ksp = kcat/KM)
      were taken from BRENDA (15, 17, and 16 values, respectively) and protein
      sequences of nine enzymes (HXK, GADH, PGK, PGM, ENO, PK, PDC, TIM, and PYC) from
      UniProtKB. The AAC and sequence properties were computed by ExPASy/ProtParam tool
      and data processed by conventional methods of multivariate statistics. Multiple
      linear regressions were found between the log-values of kcat (3 models, 85.74% <
      Radj.2 <94.11%, p < 0.00001), KM (1 model, Radj.2 = 96.70%, p < 0.00001), ksp (3
      models, 96.15% < Radj.2 < 96.50%, p < 0.00001), and the sets of AA frequencies
      (four to six for each model) selected from enzyme sequences while assessing the
      potential multicollinearity between variables. It was also found that the
      selection of independent variables in multiple regression models may reflect
      certain advantages for definite AA physicochemical and structural propensities,
      which could affect the properties of sequences. The results support the view on
      the actual interdependence of catalytic, binding, and structural residues to
      ensure the efficiency of biocatalysts, since the kinetic constants of the yeast
      enzymes appear as closely related to the overall AAC of sequences.

PMID- 22867017
TI  - Disulfide bond as a switch for copper-zinc superoxide dismutase activity in
      asthma.
AB  - AIM: Loss of superoxide dismutase (SOD) activity is a defining biochemical
      feature of asthma. However, mechanisms for the reduced activity are unknown. We
      hypothesized that loss of asthmatic SOD activity is due to greater susceptibility
      to oxidative inactivation. RESULT: Activity assays of blood samples from
      asthmatics and healthy controls revealed impaired dismutase activity of copper
      zinc SOD (CuZnSOD) in asthma. CuZnSOD purified from erythrocytes or airway
      epithelial cells from asthmatic was highly susceptible to oxidative inactivation.
      Proteomic analyses identified that inactivation was related to oxidation of
      cysteine 146 (C146), which is usually disulfide bonded to C57. The susceptibility
      of cysteines pointed to an alteration in protein structure, which is likely
      related to the loss of disulfide bond. We speculated that a shift to greater
      intracellular reducing potential might account for the change. Strikingly,
      measures of reduced and oxidized glutathione confirmed greater reducing
      intracellular state in asthma, compared with controls. Similarly, greater free
      thiol in CuZnSOD was confirmed by ~2-fold greater N-ethylmaleimide binding to
      C146 in asthma as compared with controls. INNOVATION: Greater reducing potential
      under a chronic inflammatory state of asthma, thus, leads to susceptibility of
      CuZnSOD to oxidative inactivation due to cleavage of C57-C146 disulfide bond and
      exposure of usually unavailable cysteines. CONCLUSION: Vulnerability of CuZnSOD
      influenced by redox likely amplifies injury and inflammation during acute asthma
      attacks when reactive oxygen species are explosively generated. Overall, this
      study identifies a new paradigm for understanding the chemical basis of
      inflammation, in which redox regulation of thiol availability dictates protein
      susceptibility to environmental and endogenously generated reactive species.

PMID- 22867019
TI  - New tricks for an old natural product: discovery of highly potent evodiamine
      derivatives as novel antitumor agents by systemic structure-activity relationship
      analysis and biological evaluations.
AB  - Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of
      traditional Chinese herb  Evodiae fructus . Previously, we identified N13
      substituted evodiamine derivatives as potent topoisomerase I inhibitors by
      structure-based virtual screening and lead optimization. Herein, a library of
      novel evodiamine derivatives bearing various substitutions or modified scaffold
      were synthesized. Among them, a number of evodiamine derivatives showed
      substantial increase of the antitumor activity, with GI(50) values lower than 3
      nM. Moreover, these highly potent compounds can effectively induce the apoptosis
      of A549 cells. Interestingly, further computational target prediction
      calculations in combination with biological assays confirmed that the evodiamine
      derivatives acted by dual inhibition of topoisomerases I and II. Moreover,
      several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10
      hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low
      toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates
      for the development of novel antitumor agents.

PMID- 22867021
TI  - Hemofiltration compared to hemodialysis for acute kidney injury: systematic
      review and meta-analysis.
AB  - INTRODUCTION: The objective of this systematic review and meta-analysis was to
      determine the effect of renal replacement therapy (RRT), delivered as
      hemofiltration vs. hemodialysis, on clinical outcomes in patients with acute
      kidney injury (AKI). METHODS: MEDLINE, EMBASE and CENTRAL databases and
      conference abstracts were searched to June 2012 for parallel-group or crossover
      randomized and quasi-randomized controlled trials (RCTs) evaluating
      hemofiltration vs. hemodialysis in patients with AKI. Two authors independently
      selected studies and abstracted data on study quality and outcomes. Additional
      information was obtained from trial authors. We pooled data using random-effects
      models. RESULTS: Of 6,657 citations, 19 RCTs (10 parallel-group and 9 crossover)
      met inclusion criteria. Sixteen trials used continuous RRT. Study quality was
      variable. The primary analysis included three parallel-group trials comparing
      similar doses of hemofiltration and hemodialysis; sensitivity analyses included
      trials comparing combined hemofiltration-hemodialysis or dissimilar doses. We
      found no effect of hemofiltration on mortality (risk ratio (RR) 0.96, 95%
      confidence interval (CI) 0.73 to 1.25, P = 0.76; three trials, n = 121 (primary
      analysis); RR 1.10, 95% CI 0.88 to 1.38, P = 0.38; eight trials, n = 540
      (sensitivity analysis)) or other clinical outcomes (RRT dependence in survivors,
      vasopressor use, organ dysfunction) compared to hemodialysis. Hemofiltration
      appeared to shorten time to filter failure (mean difference (MD) -7 hours, 95% CI
      (-19,+5), P = 0.24; two trials, n = 50 (primary analysis); MD -5 hours, 95% CI (
      10, -1), P = 0.01; three trials, n = 113 (including combined hemofiltration
      hemodialysis trials comparing similar doses); MD -6 hours, 95% CI (-10, -1), P =
      0.02; five trials, n = 383 (sensitivity analysis)). Data primarily from crossover
      RCTs suggested that hemofiltration increased clearance of medium to larger
      molecules, including inflammatory cytokines, compared to hemodialysis, although
      almost no studies measured changes in serum concentrations. Meta-analyses were
      based on very limited data. CONCLUSIONS: Data from small RCTs do not suggest
      beneficial clinical outcomes from hemofiltration, but confidence intervals were
      wide. Hemofiltration may increase clearance of medium to larger molecules. Larger
      trials are required to evaluate effects on clinical outcomes.

PMID- 22867023
TI  - DL-trans-3,4-dihydroxy-1-selenolane (DHS(red)) accelerates healing of
      indomethacin-induced stomach ulceration in mice.
AB  - Management of the gastro-toxicity of non-steroidal anti-inflammatory drugs
      (NSAIDs) remains a crucial problem, because the commercially available anti-ulcer
      drugs have side effects and are often expensive. Hence, the potential of a new
      water-soluble GPx mimic, DL-trans-3,4-dihydroxy-1-selenolane (DHS(red)) in
      healing the indomethacin-induced stomach ulceration in mice was examined.
      Administration of indomethacin (18 mg/kg, p. o.) induced ulceration in the
      glandular portion of the gastric mucosa, accompanied by increased lipid
      peroxidation (1.3-fold, p <0.001) and protein oxidation (1.5-fold, p < 0.001),
      depletion of thiol-defense (42.5%, p < 0.01), plasma total antioxidant status
      (53.4%, p < 0.001) and mucin (47.5%, p < 0.01), as well as reduced expressions of
      cyclooxygenases and prostaglandin synthesis (54.7%, p < 0.001) in the gastric
      tissues of mice. Daily oral administration of DHS(red) (2.5 mg/kg) or omeprazole
      (Omez) (3 mg/kg) for 3 days respectively produced ~74% and 69% (p < 0.001)
      healing of the acute gastric ulceration. The test samples also significantly
      reversed all the adverse effects of indomethacin on the biochemical parameters.
      Apparently, the gastric ulcer healing action of DHS(red) and Omez was due to
      their antioxidant action and their ability to protect mucin and augment PG
      synthesis by upregulation of the COX isozymes. The results suggested that the non
      toxic and inexpensive compound, DHS(red), may be a good candidate for further
      evaluation as a potent anti-ulcer drug.

PMID- 22867022
TI  - Attitudes of undergraduate medical students of Addis Ababa University towards
      medical practice and migration, Ethiopia.
AB  - BACKGROUND: The health care system of Ethiopia is facing a serious shortage of
      health workforce. While a number of strategies have been developed to improve the
      training and retention of medical doctors in the country, understanding the
      perceptions and attitudes of medical students towards their training, future
      practice and intent to migrate can contribute in addressing the problem. This
      study was carried out to assess the attitudes of Ethiopian medical students
      towards their training and future practice of medicine, and to identify factors
      associated with the intent to practice in rural or urban settings, or to migrate
      abroad. METHODS: A cross-sectional study was conducted in June 2009 among 600
      medical students (Year I to Internship program) of the Faculty of Medicine at
      Addis Ababa University in Ethiopia. A pre-tested self-administered structured
      questionnaire was used for data collection. Descriptive statistics were used for
      data summarization and presentation. Degree of association was measured by Chi
      Square test, with significance level set at p < 0.05. Bivariate and multivariate
      logistic regression analyses were used to assess associations. RESULTS: Only 20%
      of the students felt 'excellent' about studying medicine; followed by 'very good'
      (19%), 'good' (30%), 'fair' (21%) and 'bad' (11%). About 35% of respondents
      responded they felt the standard of medical education was below their
      expectation. Only 30% of the students said they would like to initially practice
      medicine in rural settings in Ethiopia. However, students with rural backgrounds
      were more likely than those with urban backgrounds to say they intended to
      practice medicine in rural areas (adjusted OR = 2.50, 95% CI = 1.18-5.26).
      Similarly, students in clinical training program preferred to practice medicine
      in rural areas compared to pre-clinical students (adjusted OR = 1.83, 95% CI =
      1.12-2.99). About 53% of the students (57% males vs. 46% females, p = 0.017)
      indicated aspiration to emigrate following graduation, particularly to the United
      States of America (42%) or European countries (15%). The attitude towards
      emigration was higher among Year IV (63%) and Internship (71%) students compared
      to Year I to Year III students (45-54%). Male students were more likely to say
      they would emigrate than females (adjusted OR = 1.57, 95% CI = 1.10-2.29).
      Likewise, students with clinical training were more likely to want to emigrate
      than pre-clinical students, although the difference was marginally significant
      (adjusted OR = 1.58, 95% CI = 1.00-2.49). CONCLUSIONS: The attitudes of the
      majority of Ethiopian medical students in the capital city towards practicing
      medicine in rural areas were found to be poor, and the intent to migrate after
      completing medical training was found to be very high among the study
      participants, creating a huge potential for brain drain. This necessitates the
      importance of improving the quality of education and career choice satisfaction,
      creating conducive training and working conditions including retention efforts
      for medical graduates to serve their nation. It follows that recruiting
      altruistic and rural background students into medical schools is likely to
      produce graduates who are more likely to practice medicine in rural settings.

PMID- 22867024
TI  - Cellular elements for seeing in the dark: voltage-dependent conductances in
      cockroach photoreceptors.
AB  - BACKGROUND: The importance of voltage-dependent conductances in sensory
      information processing is well-established in insect photoreceptors. Here we
      present the characterization of electrical properties in photoreceptors of the
      cockroach (Periplaneta americana), a nocturnal insect with a visual system
      adapted for dim light. RESULTS: Whole-cell patch-clamped photoreceptors had high
      capacitances and input resistances, indicating large photosensitive rhabdomeres
      suitable for efficient photon capture and amplification of small photocurrents at
      low light levels. Two voltage-dependent potassium conductances were found in the
      photoreceptors: a delayed rectifier type (KDR) and a fast transient inactivating
      type (KA). Activation of KDR occurred during physiological voltage responses
      induced by light stimulation, whereas KA was nearly fully inactivated already at
      the dark resting potential. In addition, hyperpolarization of photoreceptors
      activated a small-amplitude inward-rectifying (IR) current mediated at least
      partially by chloride. Computer simulations showed that KDR shapes light
      responses by opposing the light-induced depolarization and speeding up the
      membrane time constant, whereas KA and IR have a negligible role in the majority
      of cells. However, larger KA conductances were found in smaller and rapidly
      adapting photoreceptors, where KA could have a functional role. CONCLUSIONS: The
      relative expression of KA and KDR in cockroach photoreceptors was opposite to the
      previously hypothesized framework for dark-active insects, necessitating further
      comparative work on the conductances. In general, the varying deployment of
      stereotypical K+ conductances in insect photoreceptors highlights their
      functional flexibility in neural coding.

PMID- 22867025
TI  - Nonexclusive fluorescent sensing for L/D enantiomers enabled by dynamic
      nanoparticle-nanorod assemblies.
AB  - Fluorescence sensing of enantiomers is a much needed yet very challenging task
      due to nearly identical chemical and physical properties of the chiral isomers
      also known as chiral equivalence. In this study, we propose a novel strategy for
      fluorescence sensing of enantiomers using chiral nanoparticles and their ability
      to form dynamic assemblies. Fluorescence resonance energy transfer (FRET) in
      nanoscale assemblies consisting of either L-cysteine- or D-cysteine-modified
      quantum dots (QDs) and gold nanorods (GNRs) was found to be strongly dependent on
      traces of cysteine. This occurs due to high sensitivity of dynamic assemblies to
      the weak internanoparticle interactions that can exponentially increase energy
      transfer efficiencies from QDs to GNRs. Comprehensive analysis of the
      fluorescence responses in the two types of chiral nanoscale assemblies enables
      accurate determination of both concentration and enantiomeric composition of the
      analyte, i.e., cysteine. The described method can quantify the composition of a
      chiral sample, even the content of one enantiomer is as low as 10% in the
      mixture. Exceptional selectivity in respect to D/L-cysteine in comparison to
      analogous small molecules was observed. Versatility of nanoparticle-nanorod
      assemblies and tunability of intermolecular interactions in them open the road to
      adaptation of this sensing platform to other chiral analytes.

PMID- 22867026
TI  - The ADDOPT study (Acupuncture to Decrease Disparities in Outcomes of Pain
      Treatment): feasibility of offering acupuncture in the community health center
      setting.
AB  - OBJECTIVES: This article describes the feasibility and acceptability of the
      Acupuncture to Decrease Disparities in Outcomes of Pain Treatment (ADDOPT) trial,
      which incorporates acupuncture as an adjunct to usual treatment for chronic pain
      in urban health centers. DESIGN: The study assessed feasibility (ability to carry
      out in real-world practice; adequacy of resources; acceptability to patients,
      acupuncturists, and primary care clinicians). SETTING: Four (4) community health
      centers in the Bronx, NY, participating in the New York City Research and
      Improvement Networking Group (NYC RING), a practice-based research network
      dedicated to decreasing health disparities through primary care research and
      quality improvement in the urban safety net setting, were involved. SUBJECTS: The
      subjects comprised participants receiving care for chronic pain due to
      osteoarthritis, or neck or back pain at four Bronx health centers serving low
      income families. INTERVENTION: The intervention involved up to 14 weekly
      acupuncture treatments. OUTCOME MEASURES: Pain and functional status are assessed
      during a 6-week run-in period before, during, and postacupuncture treatment using
      the Brief Pain Inventory and the 12-Item Short Form Health Survey. This article
      reports on baseline status, referral and recruitment, engagement with treatment,
      and delivery of the intervention across sites. RESULTS: Of 400 patients referred,
      185 have initiated treatment. The majority of attending physicians have referred,
      most commonly for back pain (n=103; 60.6%). Participants' average age is 53.9
      (standard deviation [SD] 14.1); 54.1% are Hispanic; and 57.6% are on Medicaid.
      Half (48%) report "poor" or "fair" overall health. Patients report an average
      disability score of 74 (SD 27.0) and baseline pain severity on the Brief Pain
      Inventory of 6 (SD 1.9). Patients have completed a mean of 8.0 (SD 4.7)
      treatments; 72.4% complete >5 sessions. CONCLUSIONS: Clinicians in this urban
      setting have incorporated acupuncture into chronic pain management. Despite
      disability and lack of familiarity, patients initiate acupuncture and show high
      levels of engagement with treatment.

PMID- 22867027
TI  - Peer selection and influence effects on adolescent alcohol use: a stochastic
      actor-based model.
AB  - BACKGROUND: Early adolescent alcohol use is a major public health challenge.
      Without clear guidance on the causal pathways between peers and alcohol use,
      adolescent alcohol interventions may be incomplete. The objective of this study
      is to disentangle selection and influence effects associated with the dynamic
      interplay of adolescent friendships and alcohol use. METHODS: The study analyzes
      data from Add Health, a longitudinal survey of seventh through eleventh grade
      U.S. students enrolled between 1995 and 1996. A stochastic actor-based model is
      used to model the co-evolution of alcohol use and friendship connections.
      RESULTS: Selection effects play a significant role in the creation of peer
      clusters with similar alcohol use. Friendship nominations between two students
      who shared the same alcohol use frequency were 3.60 (95% CI: 2.01-9.62) times
      more likely than between otherwise identical students with differing alcohol use
      frequency. The model controlled for alternative pathways to friendship nomination
      including reciprocity, transitivity, and similarities in age, gender, and
      race/ethnicity. The simulation model did not support a significant friends'
      influence effect on alcohol behavior. CONCLUSIONS: The findings suggest that peer
      selection plays a major role in alcohol use behavior among adolescent friends.
      Our simulation results would lend themselves to adolescent alcohol abuse
      interventions that leverage adolescent social network characteristics.

PMID- 22867029
TI  - A mobile precursor determines amyloid-beta peptide fibril formation at
      interfaces.
AB  - The aggregation of peptides into amyloid fibrils plays a crucial role in various
      neurodegenerative diseases. While it has been generally recognized that fibril
      formation in vivo may be greatly assisted or accelerated by molecular surfaces,
      such as cell membranes, little is known about the mechanism of surface-mediated
      fibrillation. Here we study the role of adsorbed Alzheimer's amyloid-beta peptide
      (Abeta42) on surface-mediated fibrillation using polymer coatings of varying
      hydrophobicity as well a supported lipid bilayer membrane. Using single molecule
      fluorescent tracking and atomic force microscopy imaging, we show that weakly
      adsorbed peptides with two-dimensional diffusivity are critical precursors to
      fibril growth on surfaces. This growth mechanism is inhibited on the highly
      hydrophilic surface where the surface coverage of adsorbed peptides is negligible
      or on the highly hydrophobic surface where the diffusion constant of the majority
      of adsorbed peptides is too low. Physical properties that favor weakly adsorbed
      peptides with sufficient translational mobility can locally concentrate peptide
      molecules on the surface and promote inter-peptide interaction via two
      dimensional confinement, leading to fibrillation at Abeta peptide concentration
      many orders of magnitude below the critical concentration for fibrillation in the
      bulk solution.

PMID- 22867028
TI  - Virulence profile of different phylogenetic groups of locally isolated community
      acquired uropathogenic E. coli from Faisalabad region of Pakistan.
AB  - BACKGROUND: Uropathogenic E.coli (UPEC) are among major pathogens causing urinary
      tract infections. Virulence factors are mainly responsible for the severity of
      these emerging infections. This study was planned to investigate the distribution
      of virulence genes and cytotoxic effects of UPEC isolates with reference to
      phylogenetic groups (B2, B1, D and A) to understand the presence and impact of
      virulence factors in the severity of infection in Faisalabad region of Pakistan.
      METHODS: In this study phylogenetic analysis, virulence gene identification and
      cytotoxicity of 59 uropathogenic E.coli isolates obtained from non-hospitalized
      patients was studied. RESULTS: Among 59 isolates, phylogenetic group B2 (50%) was
      most dominant followed by groups A, B1 (19% each) and D (12%). Isolates present
      in group D showed highest presence of virulence genes. The prevalence hlyA (37%)
      was highest followed by sfaDE (27%), papC (24%), cnf1 (20%), eaeA (19%) and
      afaBC3 (14%). Highly hemolytic and highly verotoxic isolates mainly belonged to
      group D and B2. We also found two isolates with simultaneous presence of three
      fimbrial adhesin genes present on pap, afa, and sfa operons. This has not been
      reported before and underlines the dynamic nature of these UPEC isolates.
      CONCLUSIONS: It was concluded that in local UPEC isolates from non-hospitalized
      patients, group B2 was more prevalent. However, group D isolates were most
      versatile as all were equipped with virulence genes and showed highest level of
      cytotoxicity.

PMID- 22867030
TI  - Computational approach for fast screening of small molecular candidates to
      inhibit crystallization in amorphous drugs.
AB  - The applicability of the computational docking approach was investigated to
      create a novel method for quick additive screening to inhibit the crystallization
      taking place in amorphous drugs. Surface energy and attachment energy were
      utilized to recognize the morphologically most important crystal faces. The
      surfaces (100), (001), and (010) were identified as target faces, and the
      estimated free energies of binding of additives on these surfaces were
      computationally determined. The molecule of the crystallizing compound was
      included in the group of the modeled additives as the reference and for the
      validation of the approach. Additives having a lower estimated free energy of
      binding than the reference molecule itself were considered as potential
      crystallization inhibitors. Salicylamide, salicylic acid, and sulfanilamide with
      computationally prescreened additives were melt-quenched, and the nucleation and
      crystal growth rates were subsequently monitored by polarized light microscopy.
      As a result, computationally screened additives decelerated the nucleation and
      crystal growth rates of the studied drugs while the pure drugs crystallized too
      fast to be measured. The use of a computational approach enabled fast and cost
      effective additive selection to retard nucleation and crystal growth, thus
      facilitating the production of amorphous binary small molecular compounds with
      stabilized disordered structures.

PMID- 22867032
TI  - Strabismus after inferior-medial wall orbital decompression in thyroid-related
      orbitopathy.
AB  - PURPOSE: To evaluate the rate and pattern of new-onset diplopia after inferior
      medial wall orbital decompression in thyroid-related orbitopathy (TRO) patients.
      METHODS: Medical records of TRO patients who underwent orbital floor and medial
      wall decompression at the Goldschleger Eye Institute, Sheba Medical Center
      between 1/1986 and 12/2007 were reviewed and analyzed. MAIN OUTCOME MEASURES:
      primary- and down-gaze diplopia, strabismus (prism diopter [PD]). RESULTS: Fifty
      one TRO patients (30 females, mean age of 51 years) underwent 102 bilateral
      inferior-medial wall orbital decompressions. Preoperatively, 29 patients (57%)
      reported primary gaze diplopia. Of these, 13 patients (45%) had persistent or
      worsened diplopia postoperatively, all of which required strabismus surgery.
      Fifteen patients had no primary gaze diplopia preoperatively. Of these, five
      patients (33%) had new-onset diplopia postoperatively, and only one patient (7%)
      required strabismus surgery. No data regarding pre-existing diplopia were
      available in seven patients. Orbital decompression had a significant effect on
      horizontal ocular deviations with increasing esotropic shift. Primary position
      esotropia increased from 11.1 (+/- 22.5) PD preoperatively to 23.8 (+/- 20.5) PD
      after surgery (p = 0.01, paired samples t-test). No severe complications were
      encountered in this group of patients. CONCLUSIONS: Inferior-medial wall orbital
      decompression is associated with a relatively high rate of new-onset diplopia of
      up to 33%. Patients with pre-existing primary and/or downgaze diplopia are more
      likely to have persistent symptoms postoperatively that may require strabismus
      surgery.

PMID- 22867031
TI  - Quantitative and qualitative assessment of structural magnetic resonance imaging
      data in a two-center study.
AB  - BACKGROUND: Multi-center magnetic resonance imaging (MRI) studies present an
      opportunity to advance research by pooling data. However, brain measurements
      derived from MR-images are susceptible to differences in MR-sequence parameters.
      It is therefore necessary to determine whether there is an interaction between
      the sequence parameters and the effect of interest, and to minimise any such
      interaction by careful choice of acquisition parameters. As an exemplar of the
      issues involved in multi-center studies, we present data from a study in which we
      aimed to optimize a set of volumetric MRI-protocols to define a protocol giving
      data that are consistent and reproducible across two centers and over time.
      METHODS: Optimization was achieved based on data quality and quantitative
      measures, in our case using FreeSurfer and Voxel Based Morphometry approaches.
      Our approach consisted of a series of five comparisons. Firstly, a single-center
      dataset was collected, using a range of candidate pulse-sequences and parameters
      chosen on the basis of previous literature. Based on initial results, a number of
      minor changes were implemented to optimize the pulse-sequences, and a second
      single-center dataset was collected. FreeSurfer data quality measures were
      compared between datasets in order to determine the best performing sequence(s),
      which were taken forward to the next stage of testing. We subsequently acquired
      short-term and long-term two-center reproducibility data, and quantitative
      measures were again assessed to determine the protocol with the highest
      reproducibility across centers. Effects of a scanner software and hardware
      upgrade on the reproducibility of the protocols at one of the centers were also
      evaluated. RESULTS: Assessing the quality measures from the first two datasets
      allowed us to define artefact-free protocols, all with high image quality as
      assessed by FreeSurfer. Comparing the quantitative test and retest measures, we
      found high within-center reproducibility for all protocols, but lower between
      center reproducibility for some protocols than others. The upgrade showed no
      important effects. CONCLUSIONS: We were able to determine (for the scanners used
      in this study) an optimised protocol, which gave the highest within- and between
      center reproducibility of those assessed, and give details of this protocol here.
      More generally, we discuss some of the issues raised by multi-center studies and
      describe a methodical approach to take towards optimization and standardization,
      and recommend performing this kind of procedure to other investigators.

PMID- 22867033
TI  - Role of solvent parameters in the regeneration of cellulose from ionic liquid
      solutions.
AB  - The ionic liquids 1-ethyl-3-methylimidazolium acetate [emim]OAc, N,N,N,N
      tetramethylguanidium propionate [TMGH]EtCO(2), and N,N,N,N-tetramethylguanidium
      acetate [TMGH]OAc, and the traditional cellulose solvent N-methylmorpholine N
      oxide NMMO were characterized for their Kamlet-Taft (KT) values at several water
      contents and temperatures. For the ionic liquids and NMMO, thresholds of
      regeneration of cellulose solutions by water were determined using nephelometry
      and rheometry. Regeneration from wet IL was found to be asymmetric compared to
      dissolution into wet IL. KT parameters were found to remain almost constant at
      temperatures, between 20-100  degrees C, even at different water contents. Among
      the KT parameters, the beta value was found to change most drastically, with an
      almost linear decrease upon addition of water. The ability of the mixtures to
      dissolve cellulose was best explained by the difference beta-alpha (net
      basicity), rather than beta alone. Regeneration of cellulose starts at thresholds
      values of approximately beta < 0.8 (beta-alpha < 0.35) and displayed four phases.

PMID- 22867034
TI  - Novel chemosensor for the visual detection of copper(II) in aqueous solution at
      the ppm level.
AB  - A new water-soluble, multisite-coordinating ligand LH(7) was prepared by the
      condensation of tris(hydroxymethyl)aminomethane with 2,6-diformyl-p-cresol. LH(7)
      is a selective chemosensor for Cu(2+), under physiological conditions, with
      visual detection limits of 20 ppm (ambient light conditions) and 4 ppm (UV light
      conditions). LH(7) can also be used in biological cell lines for the detection of
      Cu(2+).

PMID- 22867035
TI  - Torque measurements reveal large process differences between materials during
      high solid enzymatic hydrolysis of pretreated lignocellulose.
AB  - BACKGROUND: A common trend in the research on 2nd generation bioethanol is the
      focus on intensifying the process and increasing the concentration of water
      insoluble solids (WIS) throughout the process. However, increasing the WIS
      content is not without problems. For example, the viscosity of pretreated
      lignocellulosic materials is known to increase drastically with increasing WIS
      content. Further, at elevated viscosities, problems arise related to poor mixing
      of the material, such as poor distribution of the enzymes and/or difficulties
      with temperature and pH control, which results in possible yield reduction.
      Achieving good mixing is unfortunately not without cost, since the power
      requirements needed to operate the impeller at high viscosities can be
      substantial. This highly important scale-up problem can easily be overlooked.
      RESULTS: In this work, we monitor the impeller torque (and hence power input) in
      a stirred tank reactor throughout high solid enzymatic hydrolysis (< 20% WIS) of
      steam-pretreated Arundo donax and spruce. Two different process modes were
      evaluated, where either the impeller speed or the impeller power input was kept
      constant. Results from hydrolysis experiments at a fixed impeller speed of 10 rpm
      show that a very rapid decrease in impeller torque is experienced during
      hydrolysis of pretreated arundo (i.e. it loses its fiber network strength),
      whereas the fiber strength is retained for a longer time within the spruce
      material. This translates into a relatively low, rather WIS independent, energy
      input for arundo whereas the stirring power demand for spruce is substantially
      larger and quite WIS dependent. By operating the impeller at a constant power
      input (instead of a constant impeller speed) it is shown that power input greatly
      affects the glucose yield of pretreated spruce whereas the hydrolysis of arundo
      seems unaffected. CONCLUSIONS: The results clearly highlight the large
      differences between the arundo and spruce materials, both in terms of needed
      energy input, and glucose yields. The impact of power input on glucose yield is
      furthermore shown to vary significantly between the materials, with spruce being
      very affected while arundo is not. These findings emphasize the need for
      substrate specific process solutions, where a short pre-hydrolysis (or viscosity
      reduction) might be favorable for arundo whereas fed-batch might be a better
      solution for spruce.

PMID- 22867036
TI  - Placebo-group responders in methamphetamine pharmacotherapy trials: the role of
      immediate establishment of abstinence.
AB  - Treatment responses of placebo groups in addiction medicine trials have important
      implications for research methodology and clinical practice, however studies
      examining placebo group responses in addiction medicine are scarce. Extant data
      suggest the importance of early treatment responsiveness for long-term outcomes.
      Among methamphetamine-(MA) dependent individuals randomized to placebo pill plus
      behavioral support conditions in pharmacotherapy development trials, we
      hypothesized that immediate abstinence would be a necessary but insufficient
      predictor for end-of-trial (EOT) abstinence. The study is a secondary analysis of
      participants (n = 184; 36% female) in the placebo condition of three randomized,
      placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver
      operating characteristic (ROC) curve analyses assessed the predictive power of
      initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence.
      Sixty percent of individuals with complete abstinence in the first two weeks of
      treatment were abstinent at EOT, while 18% of people who failed to meet this
      standard were abstinent at EOT. Early response was related to retention at EOT
      and 12-month follow-up. Findings suggest that the inability to achieve at least
      three MA negative screenings in the first two weeks is associated with greater
      than 90% likelihood of treatment failure. A third week of screening added
      minimally to the prediction of EOT outcomes. The prediction of treatment failure
      was more precise than the prediction of treatment success. The absence of a
      clinical response in the first two weeks of treatment among participants in the
      placebo group signals high risk of treatment failure. The majority of information
      regarding response in the placebo group from a 12-week trial is obtained early in
      the trial.

PMID- 22867037
TI  - Alternative substance paradigm: effectiveness of beverage blinding and effects on
      acute alcohol responses.
AB  - A fundamental goal of double-blind alcohol challenge studies is to reduce alcohol
      expectancies, though there is little research on the effectiveness of blinding
      procedures and their relationship to acute alcohol responses. This study examined
      social drinkers' perception of beverage content and related alcohol response
      during 3 separate double-blind experimental sessions with placebo, low-dose
      alcohol (0.4 g/kg), and high-dose alcohol (0.8 g/kg). Using the alternative
      substance paradigm, participants (N = 182) were informed that the beverage they
      consumed might contain alcohol, a stimulant, a sedative, or a placebo. At several
      time points, subjective and objective measures were obtained, and participants
      were asked to identify which substance they received. During both placebo and low
      dose alcohol sessions, 33% and 50% of participants, respectively, did not
      correctly identify the beverage content; during the high-dose alcohol session,
      20% did not correctly identify the beverage. Although correct and incorrect
      identifiers at any dose level did not differ on major background variables,
      drinking characteristics, or psychomotor performance during these sessions, they
      did differ on self-reported subjective responses, with greater sedation reported
      by incorrect identifiers in the placebo and high-dose conditions. In summary,
      results suggest that the alternative substance paradigm may be a viable option
      for alcohol laboratory studies, particularly for repeated sessions in within
      subject designs and in cases in which the experimenter wants to reduce expectancy
      by not revealing a priori that alcohol is being administered.

PMID- 22867039
TI  - Proteome analysis of pyloric ceca: a methodology for fish feed development?
AB  - Changing the protein source of fish feed from fish meal to alternative sources of
      protein will affect traits such as fish growth, quality, and feed utilization.
      The present investigation was initiated to introduce a two-dimensional gel
      electrophoresis based proteomic workflow as a tool to investigate feed effects on
      fish by analyzing protein changes in the fish gut. The workflow was used to study
      the effect of substituting fish meal in fish feed by alternative sources of
      protein. Rainbow trout divided into five groups were fed for 72 days with feeds
      varying in protein composition. By two-dimensional gel electrophoresis proteins
      extracted from the pyloric ceca were separated, making it possible to measure the
      abundance of more than 440 protein spots. The expression of 41 protein spots was
      found to change due to differences in feed composition. By mass spectrometry 31
      of these proteins were identified, including proteins involved in digestion
      (trypsinogen, carboxylic ester hydrolase, and aminopeptidase). The many
      expression changes indicated that the trout, when adapting to differences in feed
      formulation, alter the protein composition of the gut. 

PMID- 22867038
TI  - Cocaine self-administration in dopamine D3 receptor knockout mice.
AB  - The dopamine D3 receptor has received attention over the last two decades as a
      target for medications development for substance abuse disorders. Results have
      remained mixed. Despite emergence of more D3-selective ligands, possible
      attribution of observed effects to D2 receptors remains a concern. Knockout mice
      may help shed light on mechanisms. Here we evaluated the effect of constitutive
      D3 receptor inactivation ("knockout") on the reinforcing effects of cocaine. We
      tested D3 wild-type (WT), heterozygous (D3+/-), and knockout (D3-/-), mice in
      acquisition and maintenance of intravenous self-administration across a broad
      range of cocaine doses, using a fixed ratio (FR) 1 and a progressive ratio (PR)
      schedule of reinforcement, along with parallel food-reinforced studies.
      Generally, D3-/- mice showed cocaine self-administration comparable to WT
      controls across assays. Moderate and nonsignificant trends toward lesser
      reinforcing effects of a low cocaine dose (0.32 mg/kg) were apparent in
      acquisition and PR studies, consistent with the idea that the D3 receptor may
      play a subtle role in the reinforcing effects of low cocaine doses under low FR
      conditions. However, those effects with cocaine self-administration were more
      subtle than the lower responding of D3 knockout mice observed with food
      maintained behavior. In addition, the D3 antagonist PG01037 failed to affect
      cocaine self-administration under an FR 1 schedule in WT mice. The present data
      do not support a necessary role for the D3 receptor in the direct reinforcing
      effects of cocaine.

PMID- 22867040
TI  - Arachidonic acid: a bridge between traumatic brain injury and fracture healing.
AB  - Traumatic brain injury (TBI) is associated with enhanced osteogenesis. The aim of
      this study was to investigate the effect of serum from TBI rats on fracture
      healing. Results from this study showed that the serum from TBI rats enhanced the
      expression of bone gamma carboxyglutamate protein (BGLAP), and promoted in vitro
      proliferation of MC3T3-E1 cells, a mouse osteoblastic cell line. Furthermore, gas
      chromatography/mass spectrometry (GC/MS) coupled with multivariate statistical
      analysis was used to identify the changes in global serum metabolites after TBI.
      We found that arachidonic acid (AA) was significantly enhanced in serum
      metabolites in TBI subjects, while hydroxybutyric acid, leucine, malic acid, 5
      oxyproline, isocitric acid, mannose, and uric acid were reduced. Finally, we
      examined the effects of AA on BGLAP expression and cell proliferation in MC3T3-E1
      cells. We found that BGLAP expression and proliferation of osteoblasts were
      positively regulated in the presence of AA. These findings suggest that the
      increased AA in serum after TBI may play a key role in enhancing the speed of
      fracture healing.

PMID- 22867041
TI  - Avian influenza surveillance reveals presence of low pathogenic avian influenza
      viruses in poultry during 2009-2011 in the West Bengal State, India.
AB  - INTRODUCTION: More than 70 outbreaks of the highly pathogenic avian influenza
      (HPAI) H5N1 have been reported in poultry in the western and north-eastern parts
      of India. Therefore, in view of the recent HPAI H5N1 outbreaks in poultry, active
      AI surveillance encompassing wild, resident, migratory birds and poultry was
      undertaken during 2009-2011 in the State of West Bengal. METHODS: A total of 5722
      samples were collected from West Bengal; 3522 samples (2906 fecal droppings + 616
      other environmental samples) were from migratory birds and 2200 samples [1604
      tracheal, cloacal swabs, environmental samples, tissue samples + 596 blood
      (serum)] were from domestic ducks and poultry. All tracheal, cloacal and
      environmental samples were processed for virus isolation. Virus isolates were
      detected using hemagglutination assay and identified using hemagglutination
      inhibition (HI) and reverse transcriptase polymerase chain reaction (RT-PCR)
      assays. Sequencing and phylogenetic analysis of partial region of the
      hemagglutinin and neuraminidase genes was done. Intravenous pathogenicity index
      assays were performed in chickens to assess pathogenicity of AI virus isolates.
      Serum samples were tested for detection of antibodies against AI viruses using HI
      assay. RESULTS: A total of 57 AI H9N2, 15 AI H4N6 and 15 Newcastle Disease (NDV)
      viruses were isolated from chickens, from both backyard and wet poultry markets;
      AI H4N6 viruses were isolated from backyard chickens and domestic ducks.
      Characterization of AI H9N2 and H4N6 viruses revealed that they were of low
      pathogenicity. Domestic ducks were positive for antibodies against H5 and H7
      viruses while chickens were positive for presence of antibodies against AI H9N2
      and NDV. CONCLUSIONS: In the current scenario of HPAI H5N1 outbreaks in West
      Bengal, this report shows presence of low pathogenic AI H9N2 and H4N6 viruses in
      chickens and domestic ducks during the period 2009-2011. This is the first report
      of isolation of H4N6 from India. Antibodies against AI H5 and H7 in ducks
      highlight the probable role of domestic ducks in the transmission of AI viruses.
      Human infections of H9N2 have been reported from China and Hong Kong. This
      necessitates implementation of prevention and control measures to limit the
      spread of AI viruses.

PMID- 22867042
TI  - Topical testosterone supplementation for the treatment of male hypogonadism.
AB  - Age-related hormonal decline is gradual and less recognized in men than in women.
      Symptoms are oftentimes ignored and non-specific. Fatigue, lack of concentration,
      mood swings, decreased sexual desire, erectile dysfunction, infertility, hair
      loss, reduced muscle and bone mass, and weight gain are a few of the symptoms of
      male hypogonadism. This disorder is linked to reduction in quality of life, and
      poorer health outcomes as it may increase the risk for cardiovascular disease,
      diabetes mellitus, metabolic syndrome, Alzheimer's disease and premature death.
      Different modalities of testosterone replacement therapy have evolved over 70
      years, and sales continue to grow. Each preparation is differentiated by route of
      delivery, ease of use, cost and pharmacokinetics. Topical/transdermal
      testosterone replacement therapy, including patches and gels, are the most modern
      formulations on the market. These are more expensive treatments, but yield more
      physiological concentrations of testosterone. Restoration of testosterone levels
      to the eugonadal range reverses signs and symptoms of hypogonadism, except for
      infertility, and may alleviate co-morbidities associated with hypogonadism.
      Patient understanding of and compliance with both treatment and monitoring are of
      utmost importance to achieve clinical success with maximum benefit and minimum
      risk. The aim of our review is to summarize the indications, contraindications,
      benefits and risks of testosterone replacement therapy as they relate to
      transdermal administration. Further, we compare the various testosterone
      preparations, focusing on the newest topical/transdermal routes of administration
      that are currently available.

PMID- 22867043
TI  - Therapeutic management of recurrent peptic ulcer disease.
AB  - The epidemiology of peptic ulcer disease (PUD) has undergone significant changes
      since the discovery of Helicobacter pylori. Various aetiologies contribute to
      recurrent PUD. Ulcers related to untreated H. pylori infection tend to recur. Use
      of NSAIDs, low-dose aspirin and dual anti-platelet therapy have become important
      risk factors for recurrent ulcers and their complications as the proportion of H.
      pylori-related ulcers declines. Recent data have shown that H. pylori-negative,
      NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk
      of recurrent ulcer bleeding and mortality. Effective management of recurrent PUD
      relies on identification and modification of treatable risk factors. Persistent
      H. pylori infection should be carefully ruled out. Choice of an effective H.
      pylori eradication regimen should be based on local antibacterial resistance
      patterns. For patients who need long-term NSAID therapy, the initial choice of an
      NSAID relates to a patient's cardiovascular risk, and the need for therapy to
      decrease gastrointestinal (GI) complications is determined by the severity and
      number of GI risk factors. For patients on dual anti-platelet therapy, strategies
      to prevent recurrent ulcer disease and its complications centre on balancing the
      bleeding and thrombotic risks of individual patients. Long-term proton pump
      inhibitor maintenance therapy may be necessary to prevent recurrent ulcer
      bleeding for patients with ulcer bleeding from H. pylori-negative, NSAID-negative
      ulcers, and for patients who require NSAID or aspirin maintenance therapy.

PMID- 22867044
TI  - Managing post-transplant lymphoproliferative disorders in solid-organ transplant
      recipients: a review of immunosuppressant regimens.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of
      potentially life-threatening complications that occur after solid organ and bone
      marrow transplantation. Risk factors for acquiring PTLD are type of organ
      transplanted, age, intensity of immunosuppression, viral infections such as
      Epstein-Barr virus (EBV) and time after transplantation. Due to a dearth of well
      designed prospective trials, treatment for PTLD is often empirical, with
      reduction in immunosuppression accepted as the first step. Rituximab, a
      monoclonal antibody directed against the CD20 antigen of immature B cells, is
      often used as monotherapy after reduction in immunosuppression, although this is
      associated with a high risk of relapse if patients have at least one of the
      following risk factors: age greater than 60 years, elevated lactate dehydrogenase
      levels and Eastern Cooperative Oncology Group Score between 2 and 4. For such
      patients, rituximab should be considered in combination with CHOP
      (cyclophosphamide, doxorubicin, vincristine and prednisone), particularly if high
      grade PTLD is present. Although widely prescribed, the use of ganciclovir for
      PTLD remains controversial as EBV-transformed cells lack the thymidine kinase
      necessary for ganciclovir activation. Newer antivirals that combine ganciclovir
      with activators of cellular thymidine kinase have shown promising results in
      preclinical studies. In the absence of controlled trials, surgery may be
      indicated for localized disease and radiotherapy for patients with impending
      spinal cord compression or disease localized to the central nervous system or
      orbit. Future interventions may include adoptive immunotherapy, intravenous
      immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies
      to interleukin-6 and galectin-1, and even EBV vaccination. Although several
      trials are in progress, it is necessary to wait for the long-term outcome of
      these studies on risk of PTLD relapse.

PMID- 22867046
TI  - Exenatide extended-release: a review of its use in type 2 diabetes mellitus.
AB  - Subcutaneous exenatide extended-release (ER; BydureonTM; also known as exenatide
      once weekly), a glucagon-like peptide-1 receptor agonist, provides a convenient,
      simple, once-weekly regimen that is approved in adult patients with type 2
      diabetes as adjunctive monotherapy to diet plus exercise (in the US; not as first
      line therapy) and/or as combination therapy with specific oral antihyperglycaemic
      drugs (OADs) in patients with inadequately controlled type 2 diabetes despite
      treatment with these OADs (US and Europe). This article reviews the clinical
      efficacy and tolerability of exenatide ER in the treatment of adult patients with
      type 2 diabetes and gives a brief overview of its pharmacological properties. In
      several short-term (24-30 weeks) well designed trials, adjunctive subcutaneously
      injectable exenatide ER once weekly, as monotherapy or in combination with OADs,
      significantly improved glycaemic control, bodyweight and some surrogate markers
      of cardiovascular risk in adult patients with inadequately controlled type 2
      diabetes despite diet and exercise and/or treatment with OADs. Furthermore, the
      beneficial effects of adjunctive exenatide ER therapy were sustained in extension
      studies of up to 3 years of treatment. Overall, the intensity of glycaemic
      control with exenatide ER was generally better than that observed with the
      exenatide immediate-release formulation (twice daily), sitagliptin or insulin
      glargine. Exenatide ER was shown to be noninferior to metformin in terms of
      glycaemic efficacy, but did not meet the criteria for noninferiority versus
      liraglutide. In treatment-naive patients, exenatide ER treatment did not meet
      noninferiority criteria versus pioglitazone, whereas in treatment-experienced
      patients, exenatide ER provided better glycaemic control than pioglitazone.
      Improvements in glycaemic control with exenatide ER and, in general, with other
      antihyperglycaemic agents were reflected in significant improvements from
      baseline in treatment satisfaction and health-related quality-of-life measures.
      Exenatide ER was generally well tolerated in patients participating in these
      trials, with most treatment-emergent adverse events being of a gastrointestinal
      nature, of mild to moderate severity, transient and of a similar nature and
      incidence to those occurring with the exenatide immediate-release formulation.
      Thus, exenatide ER is a useful option for the treatment of type 2 diabetes,
      particularly in patients where bodyweight loss is an essential aspect of the
      individual patient's management.

PMID- 22867048
TI  - Yo-Yo IR2 testing of elite and sub-elite soccer players: performance, heart rate
      response and correlations to other interval tests.
AB  - We examined performance, heart rate response and construct validity of the Yo-Yo
      IR2 test by testing 111 elite and 92 sub-elite soccer players from Norway and
      Denmark. VO2max, Yo-Yo IR1 and repeated sprint tests (RSA) (n = 51) and match
      analyses (n = 39) were also performed. Yo-Yo IR2 and Yo-Yo IR1 performance was 41
      and 25% better (P < 0.01) for elite than sub-elite players, respectively, and
      heart rate after 2 and 4 min of the Yo-Yo IR2 test was 20 and 15 bpm (9 and 6%
      HRmax), respectively, lower (P < 0.01) for elite players. RSA performance and
      VO2max was not different between competitive levels (P > 0.05). For top-teams, Yo
      Yo IR2 performance (28%) and sprinting distance (25%) during match were greater
      (P < 0.05) than for bottom-teams. For elite and sub-elite players, Yo-Yo IR2
      performance was correlated (P < 0.05) with Yo-Yo IR1 performance (r = 0.74 and
      0.76) and mean RSA time (r = -0.74 and -0.34). We conclude that the Yo-Yo IR2
      test has a high discriminant and concurrent validity, as it discriminates between
      players of different within- and between-league competitive levels and is
      correlated to other frequently used intermittent elite soccer tests.

PMID- 22867045
TI  - Analgesics in patients with hepatic impairment: pharmacology and clinical
      implications.
AB  - The physiological changes that accompany hepatic impairment alter drug
      disposition. Porto-systemic shunting might decrease the first-pass metabolism of
      a drug and lead to increased oral bioavailability of highly extracted drugs.
      Distribution can also be altered as a result of impaired production of drug
      binding proteins or changes in body composition. Furthermore, the activity and
      capacity of hepatic drug metabolizing enzymes might be affected to various
      degrees in patients with chronic liver disease. These changes would result in
      increased concentrations and reduced plasma clearance of drugs, which is often
      difficult to predict. The pharmacology of analgesics is also altered in liver
      disease. Pain management in hepatically impaired patients is challenging owing to
      a lack of evidence-based guidelines for the use of analgesics in this population.
      Complications such as bleeding due to antiplatelet activity, gastrointestinal
      irritation, and renal failure are more likely to occur with nonsteroidal anti
      inflammatory drugs in patients with severe hepatic impairment. Thus, this
      analgesic class should be avoided in this population. The pharmacokinetic
      parameters of paracetamol (acetaminophen) are altered in patients with severe
      liver disease, but the short-term use of this drug at reduced doses (2 grams
      daily) appears to be safe in patients with non-alcoholic liver disease. The
      disposition of a large number of opioid drugs is affected in the presence of
      hepatic impairment. Certain opioids such as codeine or tramadol, for instance,
      rely on hepatic biotransformation to active metabolites. A possible reduction of
      their analgesic effect would be the expected pharmacodynamic consequence of
      hepatic impairment. Some opioids, such as pethidine (meperidine), have toxic
      metabolites. The slower elimination of these metabolites can result in an
      increased risk of toxicity in patients with liver disease, and these drugs should
      be avoided in this population. The drug clearance of a number of opioids, such as
      morphine, oxycodone, tramadol and alfentanil, might be decreased in moderate or
      severe hepatic impairment. For the highly excreted morphine, hydromorphone and
      oxycodone, an important increase in bioavailability occurs after oral
      administration in patients with hepatic impairment. Lower doses and/or longer
      administration intervals should be used when these opioids are administered to
      patients with liver disease to avoid the risk of accumulation and the potential
      increase of adverse effects. Finally, the pharmacokinetics of phenylpiperidine
      opioids such as fentanyl, sufentanil and remifentanil appear to be unaffected in
      hepatic disease. All opioid drugs can precipitate or aggravate hepatic
      encephalopathy in patients with severe liver disease, thus requiring cautious use
      and careful monitoring.

PMID- 22867049
TI  - alpha-Glucosidase inhibitory hydrolyzable tannins from Eugenia jambolana seeds.
AB  - Three new hydrolyzable tannins including two gallotannins, jamutannins A (1) and
      B (2), and an ellagitannin, iso-oenothein C (3), along with eight known phenolic
      compounds were isolated from the seeds of Eugenia jambolana fruit. The structures
      were elucidated on the basis of spectroscopic data analysis. All compounds
      isolated were evaluated for alpha-glucosidase inhibitory effects compared to the
      clinical drug acarbose.

PMID- 22867050
TI  - Lipid peroxidation product 4-hydroxy-2-nonenal promotes seeding-capable oligomer
      formation and cell-to-cell transfer of alpha-synuclein.
AB  - AIMS: Abnormal accumulation of alpha-synuclein aggregates is one of the key
      pathological features of many neurodegenerative movement disorders and dementias.
      These pathological aggregates propagate into larger brain regions as the disease
      progresses, with the associated clinical symptoms becoming increasingly severe
      and complex. However, the factors that induce alpha-synuclein aggregation and
      spreading of the aggregates remain elusive. Herein, we have evaluated the effects
      of the major lipid peroxidation byproduct 4-hydroxy-2-nonenal (HNE) on alpha
      synuclein oligomerization and cell-to-cell transmission of this protein. RESULTS:
      Incubation with HNE promoted the oligomerization of recombinant human alpha
      synuclein via adduct formation at the lysine and histidine residues. HNE-induced
      alpha-synuclein oligomers evidence a little beta-sheet structure and are distinct
      from amyloid fibrils at both conformation and ultrastructure levels.
      Nevertheless, the HNE-induced oligomers are capable of seeding the
      amyloidogenesis of monomeric alpha-synuclein under in vitro conditions. When
      neuronal cells were treated with HNE, both the translocation of alpha-synuclein
      into vesicles and the release of this protein from cells were increased. Neuronal
      cells can internalize HNE-modified alpha-synuclein oligomers, and HNE treatment
      increased the cell-to-cell transfer of alpha-synuclein proteins. INNOVATION AND
      CONCLUSION: These results indicate that HNE induces the oligomerization of alpha
      synuclein through covalent modification and promotes the cell-to-cell transfer of
      seeding-capable oligomers, thereby contributing to both the initiation and spread
      of alpha-synuclein aggregates.

PMID- 22867051
TI  - CDKL5 gene status in female patients with epilepsy and Rett-like features: two
      new mutations in the catalytic domain.
AB  - BACKGROUND: Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) located
      in the Xp22 region have been shown to cause a subset of atypical Rett syndrome
      with infantile spasms or early seizures starting in the first postnatal months.
      METHODS: We performed mutation screening of CDKL5 in 60 female patients who had
      been identified as negative for the methyl CpG-binding protein 2 gene (MECP2)
      mutations, but who had current or past epilepsy, regardless of the age of onset,
      type, and severity. All the exons in the CDKL5 gene and their neighbouring
      sequences were examined, and CDKL5 rearrangements were studied by multiplex
      ligation-dependent probe amplification (MLPA). RESULTS: Six previously
      unidentified DNA changes were detected, two of which were disease-causing
      mutations in the catalytic domain: a frameshift mutation (c.509_510insGT;
      p.Glu170GlyfsX36) and a complete deletion of exon 10. Both were found in patients
      with seizures that started in the first month of life. CONCLUSIONS: This study
      demonstrated the importance of CDKL5 mutations as etiological factors in
      neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5
      gene sequence and its rearrangements should be considered in females with Rett
      syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5
      months of age. This study also confirmed the usefulness of MLPA as a diagnostic
      screening method for use in clinical practice.

PMID- 22867053
TI  - Site-selective spectroscopy of garnet crystals doped with chromium ions.
AB  - Site-selective spectroscopy is a tool that can be used to uncover the presence of
      multiple sites available to optically active ions in host lattices. In this
      Article, we present techniques that can be applied to appraise the different
      sites that may occur in systems where charge compensation is required or in
      systems where such compensation is not present. We then consider some garnet
      crystals doped with chromium ions. For the Cr-doped garnets (YAG, GGG, GSGG, and
      CYMGG), we present luminescence and lifetime data over a wide temperature range,
      and infer not only the presence of different centers, but also the interaction
      among them as a function of temperature.

PMID- 22867052
TI  - MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste
      homolog 2 and inhibit migration and invasion in human esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed
      and associated with tumor metastasis in esophageal squamous cell carcinoma
      (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR
      124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors.
      However, the role of miRNAs in the regulation of EZH2 expression in human ESCC
      has not been documented. The aim of this study was to determine the role of these
      miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human
      ESCC. METHODS AND RESULTS: The expression of these miRNAs and EZH2 mRNA were
      examined by qPCR and the expression of EZH2 protein was detected by western blot.
      The role of these miRNAs in migration and invasion was studied in ESCC cell line
      (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and
      pcDNA-EZH2 plasmid (without the 3'-UTR of EZH2). Through clinical investigation,
      we found that miR-98 and miR-214 expression was significantly lower in ESCC
      tissues than in matched normal tissues, and the expression level of miR-98 and
      miR-214 was inversely correlated to EZH2 protein expression and the clinical
      features such as pathological grade, tumor stage and lymph node metastasis in
      ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly
      inhibited the migration and invasion of ESCC cells, which was reversed by
      transfection of EZH2. CONCLUSIONS: These findings suggest that decreased
      expression of miR-98 and miR-214 might promote metastasis of human ESCC by
      inducing accumulation of EZH2 protein.

PMID- 22867054
TI  - Tool, weapon, or white elephant? A realist analysis of the five phases of a
      twenty-year programme of occupational health information system implementation in
      the health sector.
AB  - BACKGROUND: Although information systems (IS) have been extensively applied in
      the health sector worldwide, few initiatives have addressed the health and safety
      of health workers, a group acknowledged to be at high risk of injury and illness,
      as well as in great shortage globally, particularly in low and middle-income
      countries. METHODS: Adapting a context-mechanism-outcome case study design, we
      analyze our team's own experience over two decades to address this gap: in two
      different Canadian provinces; and two distinct South African settings. Applying a
      realist analysis within an adapted structuration theory framing sensitive to
      power relations, we explore contextual (socio-political and technological)
      characteristics and mechanisms affecting outcomes at micro, meso and macro
      levels. RESULTS: Technological limitations hindered IS usefulness in the initial
      Canadian locale, while staffing inadequacies amid pronounced power imbalances
      affecting governance restricted IS usefulness in the subsequent Canadian
      application. Implementation in South Africa highlighted the special care needed
      to address power dynamics regarding both worker-employer relations (relevant to
      all occupational health settings) and North-south imbalances (common to all
      international interactions). Researchers, managers and front-line workers all
      view IS implementation differently; relationships amongst the workplace parties
      and between community and academic partners have been pivotal in determining
      outcome in all circumstances. Capacity building and applying creative commons and
      open source solutions are showing promise, as is international collaboration.
      CONCLUSIONS: There is worldwide consensus on the need for IS use to protect the
      health workforce. However, IS implementation is a resource-intensive undertaking;
      regardless of how carefully designed the software, contextual factors and the
      mechanisms adopted to address these are critical to mitigate threats and achieve
      outcomes of interest to all parties. Issues specific to IS development, including
      technological support and software licensing models, can also affect outcome and
      sustainability - especially in the North-south context. Careful attention must be
      given to power relations between the various stakeholders at macro, meso and
      micro levels when implementing IS. North-South-South collaborations should be
      encouraged. Governance as well as technological issues are crucial determinants
      of IS application, and ultimately whether the system is seen as a tool, weapon,
      or white elephant by the various involved parties."You may call me a fool, But
      was there a rule The weapon should be turned into a tool? And what do we see? The
      first tool I step on Turned into a weapon. - Robert Frost""White (albino)
      elephants were regarded as holy in ancient times in Thailand and other Asian
      countries. Keeping a white elephant was a very expensive undertaking, since the
      owner had to provide the elephant with special food and provide access for people
      who wanted to worship it. If a Thai King became dissatisfied with a subordinate,
      he would give him a white elephant. The gift would, in most cases, ruin the
      recipient. - The Phrase Finder"

PMID- 22867056
TI  - pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin
      cocrystals in aqueous media.
AB  - Cocrystals constitute an important class of pharmaceutical solids for their
      remarkable ability to modulate solubility and pH dependence of water insoluble
      drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and
      carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity
      different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times
      higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times
      higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH
      predicted from mathematical models using cocrystal K(sp), and cocrystal component
      K(a) values, was in excellent agreement with experimental measurements. The
      cocrystal solubility increase relative to drug was predicted to reach a limiting
      value for a cocrystal with two acidic components. This limiting value is
      determined by the ionization constants of cocrystal components. Eutectic
      constants are shown to be meaningful indicators of cocrystal solubility and its
      pH dependence. The two contributions to solubility, cocrystal lattice and
      solvation, were evaluated by thermal and solubility determinations. The results
      show that solvation is the main barrier for the aqueous solubility of these drugs
      and their cocrystals, which are orders of magnitude higher than their lattice
      barriers. Cocrystal increase in solubility is thus a result of decreasing the
      solvation barrier compared to that of the drug. This work demonstrates the
      favorable properties of cocrystals and strategies that facilitate their
      meaningful characterization.

PMID- 22867055
TI  - Germinal center kinase-like kinase (GLK/MAP4K3) expression is increased in adult
      onset Still's disease and may act as an activity marker.
AB  - BACKGROUND: Germinal center kinase-like kinase (GLK, also termed MAP4K3), a
      member of the MAP4K family, may regulate gene transcription, apoptosis and immune
      inflammation in response to extracellular signals. The enhanced expression of GLK
      has been shown to correspond with disease severity in patients with systemic
      lupus erythematosus. We investigated the role of GLK in the pathogenesis of adult
      onset Still's disease, which shares some similar clinical characteristics with
      systemic lupus erythematosus. METHODS: The frequencies of circulating GLK
      expressing T-cells in 24 patients with active adult-onset Still's disease and 12
      healthy controls were determined by flow cytometry analysis. The expression
      levels of GLK proteins and transcripts were evaluated in peripheral blood
      mononuclear cells by immunoblotting and quantitative PCR. Serum levels of T
      helper (Th)17-related cytokines, including IL-1beta, IL-6, IL-17 and TNF-alpha,
      were measured by ELISA. RESULTS: Significantly higher median frequencies of
      circulating GLK-expressing T-cells were observed in patients with adult-onset
      Still's disease (31.85%) than in healthy volunteers (8.93%, P <0.001). The
      relative expression levels of GLK proteins and transcripts were also
      significantly higher in patients with adult-onset Still's disease (median, 1.74
      and 2.35, respectively) compared with those in healthy controls (0.66 and 0.92,
      respectively, both P <0.001). The disease activity scores were positively
      correlated with the frequencies of circulating GLK-expressing T-cells (r = 0.599,
      P <0.005) and the levels of GLK proteins (r = 0.435, P <0.05) or GLK transcripts
      (r = 0.452, P <0.05) in patients with adult-onset Still's disease. Among the
      examined Th17-related cytokines, elevated levels of serum IL-6 and IL-17 were
      positively correlated with the frequencies of circulating GLK-expressing T-cells
      and the levels of GLK proteins as well as transcripts in patients with adult
      onset Still's disease. GLK expression levels decreased significantly after
      effective therapy in these patients. CONCLUSIONS: Elevated expression levels of
      GLK and their positive correlation with disease activity in patients with adult
      onset Still's disease indicate that GLK may be involved in the pathogenesis and
      act as a novel activity biomarker of this disease.

PMID- 22867057
TI  - Structural control of 1A2u-to-3A2u intersystem crossing in diplatinum(II,II)
      complexes.
AB  - Analysis of variable-temperature fluorescence quantum yield and lifetime data for
      per(difluoroboro)tetrakis(pyrophosphito)diplatinate(II) ([Pt(2)(MU
      P(2)O(5)(BF(2))(2))(4)](4-), abbreviated Pt(pop-BF(2))), yields a radiative decay
      rate (k(r) = 1.7 * 10(8) s(-1)) an order of magnitude greater than that of the
      parent complex, Pt(pop). Its temperature-independent and activated intersystem
      crossing (ISC) pathways are at least 18 and 142 times slower than those of
      Pt(pop) [ISC activation energies: 2230 cm(-1) for Pt(pop-BF(2)); 1190 cm(-1) for
      Pt(pop)]. The slowdown in the temperature-independent ISC channel is attributed
      to two factors: (1) reduced spin-orbit coupling between the (1)A(2u) state and
      the mediating triplet(s), owing to increases of LMCT energies relative to the
      excited singlet; and (2) diminished access to solvent, which for Pt(pop)
      facilitates dissipation of the excess energy into solvent vibrational modes. The
      dramatic increase in E(a) is attributed to increased P-O-P framework rigidity,
      which impedes symmetry-lowering distortions, in particular asymmetric vibrations
      in the Pt(2)(P-O-P)(4) core that would allow direct (1)A(2u)-(3)A(2u) spin-orbit
      coupling.

PMID- 22867058
TI  - Use of soft heterocyclic N-donor ligands to separate actinides and lanthanides.
AB  - The removal of the most long-lived radiotoxic elements from used nuclear fuel,
      minor actinides, is foreseen as an essential step toward increasing the public
      acceptance of nuclear energy as a key component of a low-carbon energy future.
      Once removed from the remaining used fuel, these elements can be used as fuel in
      their own right in fast reactors or converted into shorter-lived or stable
      elements by transmutation prior to geological disposal. The SANEX process is
      proposed to carry out this selective separation by solvent extraction. Recent
      efforts to develop reagents capable of separating the radioactive minor actinides
      from lanthanides as part of a future strategy for the management and reprocessing
      of used nuclear fuel are reviewed. The current strategies for the reprocessing of
      PUREX raffinate are summarized, and some guiding principles for the design of
      actinide-selective reagents are defined. The development and testing of different
      classes of solvent extraction reagent are then summarized, covering some of the
      earliest ligand designs right through to the current reagents of choice,
      bis(1,2,4-triazine) ligands. Finally, we summarize research aimed at developing a
      fundamental understanding of the underlying reasons for the excellent extraction
      capabilities and high actinide/lanthanide selectivities shown by this class of
      ligands and our recent efforts to immobilize these reagents onto solid phases.

PMID- 22867060
TI  - Understanding factors that modulate HIV infection at the female genital tract
      mucosae for the rationale design of microbicides.
AB  - Women are now becoming the pivot of the epidemiological spread of HIV infection
      worldwide, especially in developing countries. Therefore, research to develop an
      efficient microbicide is now a priority for the prevention of HIV-1 acquisition
      in exposed women. However, recent disappointing failures in microbicide clinical
      trials revealed major gaps in basic and applied knowledge that hinder the
      development of effective microbicide formulations. Indeed, the inhibitory power
      of microbicide molecules may be affected by several physiological and
      immunological factors present in male and female genital tracts. Furthermore,
      mucosal crossing of HIV-1 to increase the ability to reach the submucosal target
      cells (macrophages, lymphocytes, and dendritic cells) may be modulated by
      supraepithelial factors such as seminal complement components (opsonized HIV-1),
      by epithelial factors released in the submucosal microenvironment such as
      antimicrobial soluble factors, cytokines, and chemokines, and by potent
      intraepithelial and submucosal innate immunity. The design of vaginal microbicide
      formulations should take into account an understanding of the intimate mechanisms
      involved in the crossing of HIV through the female genital mucosae, in the
      context of a mixture of both male and female genital fluids.

PMID- 22867059
TI  - The effects of glycemic control on seizures and seizure-induced excitotoxic cell
      death.
AB  - BACKGROUND: Epilepsy is the most common neurological disorder after stroke,
      affecting more than 50 million persons worldwide. Metabolic disturbances are
      often associated with epileptic seizures, but the pathogenesis of this
      relationship is poorly understood. It is known that seizures result in altered
      glucose metabolism, the reduction of intracellular energy metabolites such as
      ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates,
      such as lactate and adenosine. In particular, it has been suggested that the
      duration and extent of glucose dysregulation may be a predictor of the
      pathological outcome of status. However, little is known about neither the
      effects of glycemic control on brain metabolism nor the effects of managing
      systemic glucose concentrations in epilepsy. RESULTS: In this study, we examined
      glycemic modulation of kainate-induced seizure sensitivity and its
      neuropathological consequences. To investigate the relationship between glycemic
      modulation, seizure susceptibility and its neuropathological consequences,
      C57BL/6 mice (excitotoxin cell death resistant) were subjected to hypoglycemia or
      hyperglycemia, followed by systemic administration of kainic acid to induce
      seizures. Glycemic modulation resulted in minimal consequences with regard to
      seizure severity but increased hippocampal pathology, irrespective of whether
      mice were hypoglycemic or hyperglycemic prior to kainate administration.
      Moreover, we found that exogenous administration of glucose following kainic acid
      seizures significantly reduced the extent of hippocampal pathology in FVB/N mice
      (excitotoxin cell death susceptible) following systemic administration of kainic
      acid. CONCLUSION: These findings demonstrate that modulation of the glycemic
      index can modify the outcome of brain injury in the kainate model of seizure
      induction. Moreover, modulation of the glycemic index through glucose rescue
      greatly diminishes the extent of seizure-induced cell death following kainate
      administration. Our data support the hypothesis that deficient insulin signaling
      may represent a critical contributing factor in the susceptibility to seizure
      induced cell death and this may be an important therapeutic target.

PMID- 22867061
TI  - Improving school food: for the good of kids, with the help of kids.

PMID- 22867062
TI  - Transforming school food culture and practices.

PMID- 22867063
TI  - Making our schools "the heart of health".

PMID- 22867064
TI  - The evolution of the School Food and Farm to School Movement in the United
      States: connecting childhood health, farms, and communities.
AB  - This article provides an historical review of the evolution of the Farm to School
      movement within the larger context of school food in the United States. The Farm
      to School movement emerged amidst the growing public concern about childhood
      health and obesity, as well as increasing awareness about environmental and
      economic challenges in our food and agricultural system. It offered America's
      small and midsized farmers an alternative market while potentially improving
      student health and public awareness of healthy eating. We discuss the role of key
      stakeholders in contributing to innovative strategies, programs, and policies
      related to School Food and Farm to School. The growing involvement of larger
      school districts has helped focus attention and efforts on the persistent
      challenges related to procurement and distribution. As the Farm to School
      movement has matured and moved onto the national arena, policy, research, and
      evaluation have helped define and shape new directions. Finally, we reflect on
      what it will take to strengthen Farm to School so that it can better contribute
      to human and community health.

PMID- 22867065
TI  - Salad bars in schools. Interview by Jamie Devereaux.

PMID- 22867066
TI  - Let's move salad bars to schools: a public-private partnership to increase
      student fruit and vegetable consumption.
AB  - Few school-age youth consume the recommended amounts of fruits and vegetables,
      and increasing fruit and vegetable intake in children and adolescents is an
      important public health goal to maintain long-term good health and to decrease
      risk of chronic disease and obesity. School salad bars are an important tool to
      promote fruit and vegetable consumption among schoolchildren. Studies show that
      introduction of school salad bars increases the amount and variety of fruits and
      vegetables consumed by children in schools. However, many schools cannot afford
      the capital investment in the salad bar equipment. In 2010, the National Fruit &
      Vegetable Alliance (NFVA), United Fresh Produce Association Foundation, the Food
      Family Farming Foundation, and Whole Foods Market launched Let's Move Salad Bars
      to Schools (LMSB2S) in support of First Lady Michelle Obama's Let's Move!
      initiative. The goal of LMSB2S is to place 6000 salad bars in schools over 3
      years. As of June, 2012, over 1400 new salad bar units have been delivered to
      schools across the United States, increasing access to fruits and vegetables for
      over 700,000 students. Any K through 12 school district participating in the
      National School Lunch Program is eligible to submit an application at
      www.saladbars2schools. org/. Requests for salad bar units ($2625 each unit) are
      fulfilled through grassroots fund raising in the school community and through
      funds raised by the LMSB2S partners from corporate and foundation sources. LMSB2S
      is a model for coalition-building across many government, nonprofit, and industry
      partners to address a major public health challenge.

PMID- 22867067
TI  - Understanding school food service characteristics associated with higher
      competitive food revenues can help focus efforts to improve school food
      environments.
AB  - Many school food services sell extra foods and beverages, popularly referred to
      as "competitive foods," in addition to USDA school meals. On the basis of
      national survey data, most competitive foods and beverages selected by students
      are of low nutritional value. Recent federal legislation will allow schools that
      participate in USDA school meal programs to sell competitive foods only if the
      food items they sell meet nutrition standards based on the Dietary Guidelines for
      Americans. Concerns have been raised about the potential effects of limiting
      competitive foods on local school food service finances. However, national data
      indicate that only in a subset of schools do food services receive large amounts
      of revenues from competitive foods. These food services are typically located in
      secondary schools in more affluent districts, serving higher proportions of
      students who do not receive free or reduced price meals. Compared to other food
      services, these food services couple higher competitive food revenues with lower
      school meal participation. Increasing school meal participation could increase
      meal revenues to offset any loss of competitive food revenues. Replacing less
      healthful competitive items with healthier options could also help maintain
      school food service revenues while improving the school food environment.
      Nationally consistent nutrition standards for competitive foods may encourage
      development and marketing of healthful products.

PMID- 22867068
TI  - Causal pathways linking Farm to School to childhood obesity prevention.
AB  - Farm to School programs are rapidly gaining attention as a potential strategy for
      preventing childhood obesity; however, the causal linkages between Farm to School
      activities and health outcomes are not well documented. To capitalize on the
      increased interest in and momentum for Farm to School, researchers and
      practitioners need to move from developing and implementing evidence informed
      programs and policies to ones that are evidence-based. The purpose of this
      article is to outline a framework for facilitating an evidence base for Farm to
      School programs and policies through a systematic and coordinated approach.
      Employing the concepts of causal pathways, the authors introduce a proposed
      framework for organizing and systematically testing out multiple hypotheses (or
      potential causal links) for how, why, and under what conditions Farm to School
      Inputs and Activities may result in what Outputs, Effects, and Impacts. Using the
      causal pathways framework may help develop and test competing hypotheses,
      identify multicausality, strength, and interactions of causes, and discern the
      difference between catalysts and causes. In this article, we introduce causal
      pathways, present menus of potential independent and dependent variables from
      which to create and test causal pathways linking Farm to School interventions and
      their role in preventing childhood obesity, discuss their applicability to Farm
      to School research and practice, and outline proposed next steps for developing a
      coordinated research framework for Farm to School programs.

PMID- 22867069
TI  - A sample theory-based logic model to improve program development, implementation,
      and sustainability of Farm to School programs.
AB  - Farm to School programs hold promise to address childhood obesity. These programs
      may increase students' access to healthier foods, increase students' knowledge of
      and desire to eat these foods, and increase their consumption of them.
      Implementing Farm to School programs requires the involvement of multiple people,
      including nutrition services, educators, and food producers. Because these groups
      have not traditionally worked together and each has different goals, it is
      important to demonstrate how Farm to School programs that are designed to
      decrease childhood obesity may also address others' objectives, such as academic
      achievement and economic development. A logic model is an effective tool to help
      articulate a shared vision for how Farm to School programs may work to accomplish
      multiple goals. Furthermore, there is evidence that programs based on theory are
      more likely to be effective at changing individuals' behaviors. Logic models
      based on theory may help to explain how a program works, aid in efficient and
      sustained implementation, and support the development of a coherent evaluation
      plan. This article presents a sample theory-based logic model for Farm to School
      programs. The presented logic model is informed by the polytheoretical model for
      food and garden-based education in school settings (PMFGBE). The logic model has
      been applied to multiple settings, including Farm to School program development
      and evaluation in urban and rural school districts. This article also includes a
      brief discussion on the development of the PMFGBE, a detailed explanation of how
      Farm to School programs may enhance the curricular, physical, and social learning
      environments of schools, and suggestions for the applicability of the logic model
      for practitioners, researchers, and policy makers.

PMID- 22867070
TI  - Can schools save kids' palates? Cooking from scratch in schools--the greatest
      food service challenge of our time.
AB  - School District Food Service Departments are faced with the enormous task of
      feeding children in the United States up to two thirds of the meals that they
      consume during the week at school. The shift in food production since the 1970s
      produced a trend away from scratch-cooked foods and resulted in more meals
      created from processed foods. The United States has reached a tipping point where
      the health of the current generation is compromised by increasing health risks of
      diet-related disease. Schools have been identified as a critical environment in
      which there is an opportunity to effect change in what children eat. As a result,
      in the last 10 years, there has been a resurgence of interest in freshly prepared
      meals in schools. This article explores one chef's transition from the private
      sector to the public sector and the experiences of working with school districts
      to successfully transform their school food service operations into a scratch
      cooking model.

PMID- 22867071
TI  - School food: point of view matters.
AB  - This article discusses the origins of a new organizational effort-that of School
      Food FOCUS-structured to engage in systems level change at the intersection of
      child health, institutional school food service, and the wider food system. Now 4
      years into its program development, FOCUS has organized itself as a collaborative
      network using multiple partnerships, participatory research, and peer learning to
      procure cost-effective, healthful, and sustainably produced school meals. While
      food procurement change could be viewed as a narrow scope of work, the authors
      share their perspective about the complexity of this work, which involves
      conflicting values about food, long-established institutional practices,
      knowledge drawn from a range of disciplines, and a massive food marketing
      campaign over the past 60 years that has fundamentally changed the way that
      Americans eat, including what children eat in schools. Using the experience of
      FOCUS as a lens, the authors also highlight a number of initiatives filling in
      some of the gaps in the safety net, suggesting that multiple pathways are being
      built to address both individual and institutional food behavior change so that
      children nourished with healthy foods could become the new 'normal' in the next
      generation.

PMID- 22867072
TI  - Local wellness policy strength and perceived implementation of school nutrition
      standards across three states.
AB  - BACKGROUND: Congress sought to address escalating rates of childhood obesity by
      mandating local wellness policies (LWP) (Child Nutrition and WIC Reauthorization
      Act of 2004). Previous research has examined LWP content and quality; however,
      data relative to LWP implementation is limited, and none has examined the
      relationship between LWP quality and implementation. The purpose of this study
      was to examine the influence of LWP strength on perceived implementation of LWP
      components. METHODS: Data collected from school districts in California, Iowa,
      and Pennsylvania included district LWPs and online surveys at the district (n =
      23) and school levels (n = 76). LWPs were scored using a standardized coding
      tool. Binary and multinomial regression models were used to examine the
      predictive ability of covariates and independent factors on perceived
      implementation of reimbursable school meals and nutrition guidelines for
      competitive foods sold and offered. RESULTS: Overall LWP strength score did not
      predict perceived implementation of reimbursable school meals or nutrition
      guidelines for competitive foods. LWP component strength scores for reimbursable
      meals and nutrition guidelines did not consistently predict perceived
      implementation of those components. State and urban-centric locale did predict
      perceived implementation of some LWP components, particularly nutrition
      guidelines for competitive foods sold and offered. State was a particularly
      influential factor in the implementation of LWPs in this study, likely due to
      differences in state policies and laws. CONCLUSIONS: Overall LWP, reimbursable
      school meals, and nutrition guidelines for competitive foods strength scores do
      not predict perceived implementation of reimbursable school meals and nutrition
      guidelines for competitive foods.

PMID- 22867073
TI  - Does competitive food and beverage legislation hurt meal participation or
      revenues in high schools?
AB  - BACKGROUND: There is limited evidence to evaluate the influence of competitive
      food and beverage legislation on school meal program participation and revenues.
      METHODS: A representative sample of 56 California high schools was recruited to
      collect school-level data before (2006-2007) and the year after (2007-2008)
      policies regarding limiting competitive foods and beverages were required to be
      implemented. Data were obtained from school records, observations, and
      questionnaires. Paired t-tests assessed significance of change between the two
      time points. RESULTS: Average participation in lunch increased from 21.7% to
      25.3% (p < 0.001), representing a 17.0% increase, while average participation in
      breakfast increased from 8.9% to 10.3% (p = 0.02), representing a 16.0% increase.
      There was a significant (23.0%) increase in average meal revenue, from $0.70 to
      $0.86 (per student per day) (p < 0.001). There was a nonsignificant decrease
      (18.0%) in average sales from a la carte foods, from $0.45 to $0.37 (per student
      per day). Compliance with food and beverage standards also increased
      significantly. At end point, compliance with beverage standards was higher
      (71.0%) than compliance with food standards (65.7%). CONCLUSION: Competitive food
      and beverage legislation can increase food service revenues when accompanied by
      increased rates of participation in the meal program. Future studies collecting
      expense data will be needed to determine impact on net revenues.

PMID- 22867074
TI  - Improving healthy dietary behaviors, nutrition knowledge, and self-efficacy among
      underserved school children with parent and community involvement.
AB  - BACKGROUND: University-community partnerships through coordinated school health
      programs (CSHP) can play a key role in decreasing child obesity. The main
      objective of this study was to measure over a 1-year period whether a CSHP with
      parental, school, and home-based components to promote optimal nutrition will
      reduce BMI percentiles and z-scores and improve dietary behaviors in a sample of
      low-income, school-aged children. METHODS: The intervention included, Kids
      Nutrition and Fitness, a 6-week nutrition, physical activity educational after
      school program, and school activities, including creation of an Advisory
      Committee that made wellness policies. A randomized controlled pilot study
      evaluated the effectiveness of the intervention that contrasts 251 (n = 251)
      predominantly Mexican-American 8 to 12 year olds from low-income Los Angeles
      based schools. A mixed model of repeated measures analysis assessed changes in
      BMI percentiles and z-scores, dietary behaviors, food preferences, knowledge, and
      self-efficacy measured by a reliable/valid questionnaire. These data were
      collected at baseline and at 4 and 12 months postintervention. Process measures,
      collected via focus groups with parents, evaluated parent/community involvement.
      RESULTS: At the 12-month follow-up, children in the intervention group decreased
      their BMI on average by 2.80 (p = 0.04) and BMI z-scores on average by 0.48 (p =
      0.03) and they increased their daily dietary intake of vegetables on average by
      1.51 (p = 0.03), fruit on average by 2.00 (P = 0.001), and 100% fruit juice by
      1.12 (p = 0.05). An increase of 1.02 (p = 0.03) was seen in self-efficacy of
      healthy food choices (p = 0.03). Parent (P = 0.04) and community (p = 0.001)
      involvement significantly increased to 100% participation by the 12-month follow
      up. CONCLUSIONS: A CSHP using parent and community involvement was effective in
      reducing the risk of obesity in school-aged Mexican- American children attending
      low-income schools. The findings need to be examined in a larger, more diverse
      sample of children.

PMID- 22867075
TI  - Social cognitive theory as a framework for considering Farm to School
      programming.
AB  - BACKGROUND: Farm to School (FTS) programs are designed, in part, to improve
      childhood health and nutrition and may be implemented as a strategy to prevent
      childhood obesity. FTS programs have largely emerged out of grassroots efforts,
      and theory has not explicitly guided program development or implementation. This
      research considers the effectiveness of social cognitive theory (SCT) as a
      framework for FTS programming. METHODS: In 2010, a survey was administered to 632
      elementary schoolchildren in Vermont. Six indices were developed from 46
      variables that measured personal characteristics and experiences with regard to
      fruits and vegetables, as described in the SCT. RESULTS: These indices were the
      basis for cluster analysis, which identified three distinct clusters. Bivariate
      analysis showed significant differences among the clusters in the children's
      likelihood of meeting the Dietary Guidelines for Americans (DGA). The significant
      differences observed among the clusters suggest that SCT is an appropriate
      framework within which FTS interventions may be considered. CONCLUSIONS: The
      findings show that there are distinct food-related attitudes and behaviors that
      differ widely by the SCT informed clusters and that can be used to inform FTS
      programs.

PMID- 22867076
TI  - School lunches and lunches brought from home: a comparative analysis.
AB  - BACKGROUND: Considerable effort has been put forth to improve the nutritional
      quality of school meals by the National School Lunch Program (NSLP). However, a
      large percentage of children do not obtain their meals from school and instead
      bring lunch from home. Little research has focused on the content of these
      lunches. The purpose of the current study was to examine differences between
      school lunch and lunch brought from home. METHODS: Children in the 2nd grade from
      seven schools in a large suburban school district were observed on three separate
      days. A total of 2107 observations were made, with 38.5% of these being lunches
      brought from home. Chi-squared analyses evaluated differences in the presence of
      specific food items between school lunch and lunch brought from home. RESULTS:
      Compared to children with a school lunch, children with a lunch brought from home
      were significantly less likely to have fruits (75.9% vs. 45.3%), vegetables
      (29.1% vs. 13.2%), and dairy (70.0% vs. 41.8%) (p < 0.001). Children with a lunch
      from home were more likely to have snacks high in sugar and/or fat (17.5% vs.
      60.0%) and non 100% fruit juice/fruit drink (0.3% vs. 47.2%) (p < 0.001) than
      children with a school lunch. CONCLUSIONS: The NSLP has been widely criticized;
      however, conducting a comparison in this manner demonstrates advantages to
      children obtaining school lunches. Although it was beyond the scope of this study
      to examine diet quality (e.g., actual intake and nutrient/caloric density), these
      results provide compelling evidence that lunches brought from home should be an
      area of emphasis for research and intervention.

PMID- 22867077
TI  - A qualitative evaluation of exposure to and perceptions of the Woolworths Healthy
      Tuck Shop Guide in Cape Town, South Africa.
AB  - BACKGROUND: Both under- and over-nutrition pose a public health concern,
      especially for children in South Africa. Several initiatives exist in South
      Africa directed at promoting healthy eating and nutrition at schools. One of them
      is the Woolworths Making the Difference (MTD) Programme aimed at eliminating
      barriers to promoting healthy lifestyles that exist at schools, such as the
      availability of low-cost, unhealthy foods either from tuck shops (small food
      shops) or street vendors. The Healthy Tuck Shop Guide is a recent addition to the
      MTD Programme. The aim of this evaluation was to assess awareness, potential
      uptake, and perceptions of the Woolworths Healthy Tuck Shop Guide among parents
      and staff in a sample of schools that were exposed to the guide. METHODS: A
      qualitative study consisting of focus groups, interviews, and tuck shop
      observation was used to gather information on 13 schools and their exposure,
      comprehension, and use of the guide. A mix of schools was examined in terms of
      economic status and level of control over their tuck shop. Thematic analysis was
      used to extract findings. RESULTS: Findings show that despite overall positive
      attitudes about the guide several barriers to its implementation exist, including
      children's preferences for unhealthy foods, the higher cost of healthy foods, and
      other issues related to a lack of facilities, time and manpower. CONCLUSION:
      Findings suggest that the Woolworths Healthy Tuck Shop Guide would contribute
      more meaningfully to the creation of healthier food environments if executed
      within a larger support network to address barriers to implementation.

PMID- 22867078
TI  - Calories in the classroom: celebration foods offered and consumed during
      classroom parties at an elementary school in a low-income, urban community.
AB  - BACKGROUND: The school food environment is an important area of exploration in
      investigating the potential for schoolchildren to consume foods and beverages
      containing excess calories on school grounds. Several venues offer schoolchildren
      access to lownutrient, calorie-dense foods and beverages. Classroom celebrations
      offer such a venue; however, little is known about current practices during these
      events. METHODS: Trained observers recorded foods and beverages offered,
      activities engaged in, and goody bag distribution during six separate classroom
      celebrations. Additionally, foods and beverages consumed by 24 individual
      students were recorded in detail for calorie estimation. RESULTS: The majority of
      food items offered during classroom celebrations were low-nutrient, calorie-dense
      items. The mean caloric contribution for all 24 students was 444 +/- 221
      calories, with a range of 130-905 calories, and a median intake of 386 calories.
      Mean total estimated calorie intake per grade level was 225 +/- 90, 286 +/- 105,
      and 550 +/- 212 calories for students in prekindergarten, kindergarten, and 1st
      grade, respectively. Only one-third of all the parties observed included
      activities other than eating. CONCLUSIONS: Our observations reveal that food
      items offered during classroom celebrations offer children opportunities to
      consume low-nutrient, calorie-dense foods and beverages on the school campus.
      More research is needed to support these findings, and to identify the best
      practice to implement for effective school wellness policies aimed at regulating
      classroom celebrations.

PMID- 22867079
TI  - A "real chicken" revolution: how two large districts are shifting the school
      poultry paradigm with scratch cooking.

PMID- 22867080
TI  - Increasing access to fresh, local produce: building values-based supply chains in
      San Diego Unified School District.

PMID- 22867081
TI  - Building food literacy and positive relationships with healthy food in children
      through school gardens.

PMID- 22867082
TI  - Sowing the seeds for healthy minds and bodies.

PMID- 22867083
TI  - Fulfilling the highest nutrition standards in Burke County district schools.

PMID- 22867084
TI  - School food: success stories.

PMID- 22867086
TI  - Quercetin, resveratrol, and curcumin are indirect activators of the aryl
      hydrocarbon receptor (AHR).
AB  - Several polyphenols have been shown to activate the aryl hydrocarbon receptor
      (AHR) in spite of the fact that they bind to the receptor with low affinity. The
      aim of this study was to investigate whether quercetin (QUE), resveratrol (RES),
      and curcumin (CUR) interfere with the metabolic degradation of the suggested
      endogenous AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ) and thereby
      indirectly activate the AHR. Using recombinant human enzyme, we confirmed earlier
      reported inhibitory effects of the polyphenols on cytochrome P4501A1 (CYP1A1)
      activity, and inhibition of metabolic clearance of FICZ was documented in FICZ
      treated immortalized human keratinocytes (HaCaT). CYP1A1 activity was induced in
      HaCaT cells by all three compounds, and when they were added together with FICZ,
      a prolonged activation was observed after a dose-dependent inhibition period. The
      same pattern of responses was seen at the transcriptional level as determined
      with a CYP1A1 reporter assay in human liver hepatoma (HepG2) cells. To test the
      ability of the polyphenols to activate the AHR in the absence of FICZ, the cells
      were treated in medium, which in contrast to commercial batches of medium did not
      contain background levels of FICZ. Importantly, AHR activation was only observed
      in the commercial medium. Taken together, these findings suggest that QUE, RES,
      and CUR induce CYP1A1 in an indirect manner by inhibiting the metabolic turnover
      of FICZ. Humans are exposed to these compounds through the diet and nutritional
      supplements, and we propose that altered systemic levels of FICZ caused by such
      compounds may have physiological consequences.

PMID- 22867087
TI  - N-acyl homoserine lactone mediated interspecies interactions between A. baumannii
      and P. aeruginosa.
AB  - Acinetobacter baumannii and Pseudomonas aeruginosa are pathogens capable of
      colonizing the same infection sites and employing N-acyl homoserine lactone (AHL)
      based quorum-sensing systems to co-ordinate biofilm formation. Hence, the effect
      of P. aeruginosa AHLs on biofilm formation by A. baumannii and vice versa were
      investigated using the biofilm impaired quorum sensing mutants, A. baumannii M2
      (abaI::Km) and P. aeruginosa PAO-JP2. Complementing the mutants with
      heterologous, extracted and pure AHLs increased biofilm mass significantly. The
      surface area coverage and biovolume also increased significantly as observed by
      confocal scanning laser microscopy which corroborated scanning electron
      microscope analysis. Autoinducer synthase gene promoters of A. baumannii, P(
      abaI)-lacZ, and P. aeruginosa, P( lasI)-lacZ, were induced (p < 0.05) by
      heterologous AHLs. Growth of A. baumannii was not inhibited by pyocyanin of P.
      aeruginosa which may allow their co-existence and interaction in the clinical
      setting, thereby affecting the severity of combined infections and therapeutic
      measures to control them.

PMID- 22867088
TI  - Glutathione-S-transferase M1 regulation of diesel exhaust particle-induced pro
      inflammatory mediator expression in normal human bronchial epithelial cells.
AB  - BACKGROUND: Diesel exhaust particles (DEP) contribute substantially to ambient
      particulate matter (PM) air pollution in urban areas. Inhalation of PM has been
      associated with increased incidence of lung disease in susceptible populations.
      We have demonstrated that the glutathione S-transferase M1 (GSTM1) null genotype
      could aggravate DEP-induced airway inflammation in human subjects. Given the
      critical role airway epithelial cells play in the pathogenesis of airway
      inflammation, we established the GSTM1 deficiency condition in primary bronchial
      epithelial cells from human volunteers with GSTM1 sufficient genotype (GSTM1+)
      using GSTM1 shRNA to determine whether GSTM1 deficiency could exaggerate DEP
      induced expression of interleukin-8 (IL-8) and IL-1beta proteins. Furthermore,
      the mechanisms underlying GSTM1 regulation of DEP-induced IL-8 and IL-1beta
      expression were also investigated. METHODS: IL-8 and IL-1beta protein levels were
      measured using enzyme-linked immunosorbent assay. GSTM1 deficiency in primary
      human bronchial epithelial cells was achieved using lentiviral GSTM1 shRNA
      particles and verified using real-time polymerase chain reaction and
      immunoblotting. Intracellular reactive oxygen species (ROS) production was
      evaluated using flow cytometry. Phosphorylation of protein kinases was detected
      using immunoblotting. RESULTS: Exposure of primary human bronchial epithelial
      cells (GSTM1+) to 25-100 MUg/ml DEP for 24 h significantly increased IL-8 and IL
      1beta protein expression. Knockdown of GSTM1 in these cells further elevated DEP
      induced IL-8 and IL-1beta expression, implying that GSTM1 deficiency aggravated
      DEP-induced pro-inflammatory response. DEP stimulation induced the
      phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, the
      downstream kinase of phosphoinositide 3-kinase (PI3K), in GSTM1+ bronchial
      epithelial cells. Pharmacological inhibition of ERK kinase and PI3K activity
      blocked DEP-induced IL-8 and IL-1beta expression. DEP-induced ERK and Akt
      phosphorylation could be increased by GSTM1 knockdown. In addition, pretreatment
      of HBEC with the antioxidant N-acetyl cysteine significantly inhibited DEP
      induced ERK and Akt phosphorylation, and subsequent IL-8 and IL-1beta expression.
      CONCLUSION: GSTM1 regulates DEP-induced IL-8 and IL-1beta expression in primary
      human bronchial epithelial cells by modulation of ROS, ERK and Akt signaling.

PMID- 22867089
TI  - Fixed-dose combination therapy in hypertension: cons.
AB  - The goal of antihypertensive therapy is to reduce the risk associated with blood
      pressure elevation. Although the choice of first-line drug therapy may exert some
      effects on different long-term cardiovascular endpoints, randomized clinical
      trials and meta-analyses demonstrated that blood pressure reduction per se is the
      primary determinant in primary and secondary prevention. Numerous analyses
      carried out over the last years have repeatedly shown that many patients require
      the combination of two or more drugs to reach the recommended level of blood
      pressure control. Within this context, combination therapy with separate agents
      or fixed-dose combination pills offers an attractive ability to lower blood
      pressure more quickly, decrease adverse effects and reach blood pressure target.
      It is not clear whether fixed combinations of antihypertensive agents in a single
      tablet provide a greater benefit than the corresponding components given
      separately. In other words, it is not clear if the use of fixed combinations
      translates into a clearly improved blood pressure control and cardiovascular
      prevention in clinical practice. Fixed-dose combinations may simplify the
      treatment regimen by reducing the number of pills and may be attractive for many
      hypertensive patients. However, single-pill (fixed) drug combinations have some
      disadvantages: (i) branded fixed combinations may be more expensive than
      equivalent free combinations; (ii) the duration of action of individual
      components may not be equivalent, and this may not justify a single daily dosing
      of the combination; and (iii) the use of fixed combinations implies less
      flexibility in modifying the doses of individual components and the exposure of
      patients to unnecessary therapy. Moreover, should a patient develop side effects
      to one component, the entire combination should be discontinued and replaced by
      free drugs. The following three types of fixed-dose tablets have been recently
      proposed to give additional flexibility: (i) tablet manufactured so that each of
      the two drugs is placed at opposite ends of the tablet with a drug-free
      (inactive) layer placed in between; (ii) tablet with the combination of drugs at
      each end with the inactive zone in between; and (iii) tablet divided into
      discrete, separate segments (the two drugs are combined uniformly), which
      provides benefits for initial close titration and dosage adjustments. Currently,
      none of the fixed-dose tablets available on the market have these characteristics
      and, consequently, are unable to be broken to allow sufficient flexibility.

PMID- 22867090
TI  - Fixed-dose combination therapy in hypertension: pros.
AB  - Effective treatment of high blood pressure represents a key strategy for reducing
      the burden of hypertension-related cardiovascular diseases, mostly myocardial
      infarction and stroke. Despite these well established concepts, however,
      hypertension remains poorly controlled, worldwide. In addition, treated
      hypertensive patients often remain at higher risk compared with the normotensive
      population, even when a satisfactory blood pressure control is achieved, due to
      the high or very high added cardiovascular risk profile observed in these
      patients. An emerging strategy to improve blood pressure control and achieve this
      unmet target for cardiovascular disease prevention in hypertensive patients is
      represented by a more extensive use of rational and effective combination
      therapies with respect to monotherapy. Such an approach has been recently
      proposed even as first-line strategy in hypertensive patients at high added
      cardiovascular risk or in those in whom strict blood pressure control is
      required. Within the possible antihypertensive drug combinations currently
      available for the clinical management of hypertension, those based on the
      association of drugs inhibiting the renin-angiotensin system and thiazide
      diuretics or calcium channel blockers have demonstrated to be effective and safe
      in lowering both systolic and diastolic blood pressure levels with a good
      tolerability profile. In addition, these strategies have provided evidence for
      effective cardiovascular protection compared with conventional antihypertensive
      therapies. Among the antihypertensive drugs able to counteract the deleterious
      effects of abnormal activation of the renin-angiotensin system, angiotensin II
      receptor blockers have demonstrated to provide better tolerability profile and
      greater cardiovascular protection on hypertension-related organ damage compared
      with ACE inhibitors in randomized controlled clinical trials, in the presence of
      similar antihypertensive efficacy and safety. In particular, these drugs are
      characterized by lower rates of drug-related side effects, better compliance and
      adherence to prescribed antihypertensive regimens, and use in synergistic and
      rational combination therapies, all factors that may contribute to improve blood
      pressure control and reduce discontinuations from antihypertensive therapy in
      treated hypertensive patients.

PMID- 22867091
TI  - Recommending salt intake reduction to the hypertensive patient: more than just
      lip service.
AB  - The average individual dietary salt intake largely exceeds the physiological
      needs almost worldwide. A direct causal association between salt intake and blood
      pressure levels has been clearly established. Furthermore, there is increasing
      evidence for additional blood pressure-independent pathways linking excess salt
      intake to the process of atherosclerosis. Recent meta-analyses of randomized
      controlled trials showed that moderate reduction of salt intake is associated
      with reduction of blood pressure and, in perspective, with reduction of
      cardiovascular and cerebrovascular events in hypertensive individuals. According
      to the European Society of Hypertension/European Society of Cardiology (ESH/ESC)
      guidelines for the management of hypertension, instructions to reduce dietary
      salt intake to the level of 5 g/day based on the WHO recommendation should be
      provided to all patients, regardless of their requirement for drug treatment.
      Unfortunately, the patients' response to this measure is heterogeneous, mainly
      due to variable compliance with the doctor's prescription and to a lesser extent
      to different individual BP salt sensitivity. This article discusses the factors
      affecting the probability of a successful intervention focusing in particular on
      the doctor's commitment to evaluate the patient's dietary habits, to point out
      the main sources of salt in the patient's diet, to provide the patient with
      adequate motivation and with proper instructions to implement gradual reduction
      of his/her salt intake, not disregarding the need for regular follow-up.

PMID- 22867092
TI  - Healthy diet to prevent cardiovascular diseases and osteoporosis: the experience
      of the 'ProSa' project.
AB  - The ProSa (PROmozione e tutela della SAlute) Project ('Health Promotion Project')
      is a workplace programme geared to promote health among the Roman staff of the
      National Research Council of Italy. 789 employees of both genders (450 men, 339
      women) have participated in the cardiovascular prevention programme (screening,
      computerized calculation of the risk level, dietary and pharmacological
      intervention) and 245 women have participated in the osteoporosis programme
      (calcaneal ultrasonometer test, dietary and pharmacological intervention).
      Menopause increases the risk of cardiovascular diseases and osteoporosis. In
      order to lower dietary fat content, dietary intake of calcium and vitamin D could
      be reduced. However, supplementation of both may not be necessary if we follow an
      integrated dietary approach. Therefore, for women in menopause with mixed
      hyperlipidaemia (hypercholesterolaemia and/or hypertriglyceridaemia) and/or
      overweight/obesity, dietary intervention was aimed at promoting the choice of
      foods low in fats and rich in calcium based on a list of recommended products
      distributed to all the participants. The dietary intervention was accompanied by
      a programme of regular physical activity with adequate exposure to sunlight. By
      following a balanced diet it is possible to improve the prognosis not only for
      hyperlipidaemic patients, but also for patients with signs of osteopaenia or
      osteoporosis.

PMID- 22867093
TI  - An observational, prospective, open-label, multicentre evaluation of aliskiren in
      treated, uncontrolled patients: a real-life, long-term, follow-up, clinical
      practice in Italy.
AB  - INTRODUCTION: The addition of the direct renin inhibitor aliskiren is
      demonstrated to improve blood pressure (BP) control rate and reduce progression
      of organ damage in treated hypertensive patients in clinical trials with a
      relatively short follow-up period. AIM: The objective of this study was to assess
      the effectiveness, safety and tolerability of aliskiren as an add-on
      antihypertensive therapy in high-risk, treated, hypertensive patients, who were
      not controlled with concomitant treatment with at least two antihypertensive
      drugs under 'real-life' conditions, during a planned observation and treatment
      period of at least 12 months in Italy. METHODS: Clinical data were derived from
      medical databases of treated, uncontrolled, hypertensive patients followed by
      specialized physicians operating in different clinical settings (hospital
      divisions or outpatient clinics) in Italy. Aliskiren was added to stable
      antihypertensive treatment, including at least two drug classes (independently of
      class or dosage) and unable to achieve BP control. Follow-up visits for measuring
      clinic BP levels and collecting data on drug safety and tolerability were planned
      at time intervals of 1, 6 and 12 months. At each predefined follow-up visit,
      aliskiren could be up-titrated from 150 to 300 mg daily if BP control was not
      achieved. RESULTS: From May 2009 to June 2011, a total of 1186 treated,
      uncontrolled, hypertensive patients (46.3% female, aged 65.2 +/- 11.7 years, mean
      duration of hypertension 13.2 +/- 9.3 years, mean clinic BP levels 156.5 +/-
      15.9/90.3 +/- 9.5 mmHg) were enrolled. Systolic and diastolic BP levels were
      141.1/82.4, 134.9/79.8 and 133.6/78.9 mmHg at 1-, 6- and 12-month follow-up
      visits, respectively (p < 0.0001 vs baseline for all comparisons). These effects
      were consistent in all predefined subgroups, including those with left
      ventricular hypertrophy, renal disease, diabetes mellitus, coronary artery
      disease or cerebrovascular disease. Reduced levels of microalbuminuria were also
      reported, without affecting other renal and electrolyte parameters. Overall,
      compliance to study medication was high (93.0%), with a very low proportion of
      patients experiencing adverse events leading to drug discontinuation (3.6%).
      CONCLUSIONS: In this observational, prospective, open-label, multicentre study,
      we reported the 12-month clinical effectiveness, safety and tolerability of
      adding aliskiren to treated, uncontrolled, hypertensive patients in a 'real-life'
      setting in Italy. This strategy leads to a significantly improved BP control rate
      and low incidence of drug-related side effects or discontinuations.

PMID- 22867094
TI  - Lifestyle-related risk factors, smoking status and cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease represents one of the most important causes of
      morbidity and mortality in highly developed countries and is known to be
      associated with some lifestyle-related risk factors (e.g. alcohol consumption,
      smoking status, diet, physical activity, bodyweight). There is still incomplete
      information about their combined effect on cardiovascular risk in hypertensive
      patients with optimal pharmacological blood pressure control. AIM: The objective
      of this study was to evaluate the correlation of some lifestyle behaviours, using
      a specific questionnaire, with development of cardiovascular disease in treated
      hypertensive patients. METHODS: 617 hypertensive, non-diabetic participants (aged
      53.1 +/- 7.6 years, 44.9% male; mean age 53.1 +/- 7.6 years) free of prevalent
      cardiovascular disease, cancer, liver cirrhosis and/or failure, chronic kidney
      disease more than grade 3 (glomerular filtration rate by the Modification of Diet
      in Renal Disease study <30 mL/min/1.73 m2) were analysed. Metabolic syndrome was
      defined according to the Third Report of the Expert Panel on Detection,
      Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
      Panel III). Left ventricular hypertrophy was defined when left ventricular mass
      index was >51 g/m2. Carotid artery atherosclerosis was assessed as an increased
      intima medial thickness (IMT) by B-mode ultrasonography. IMT values between 0.9
      and 1.3 mm were defined as 'thickening' and those >1.3 mm as 'plaque'. Assessment
      of smoking status, dietary and non-dietary factors was established by
      administration of a specific questionnaire. RESULTS: In the initial population of
      examined patients, 288 were smokers and 329 were non-smokers. At baseline, the
      patients belonging to smoking group were less often overweight than those
      belonging to the non-smoking group, showing a lower initial body mass index (BMI)
      [27.54 +/- 4.0 vs 28.28 +/- 4.3; p < 0.029], lower plasma levels of high-density
      lipoprotein cholesterol (HDL-C) [48.14 +/- 12.6 vs 51.39 +/- 14.1 mg/dL; p <
      0.006] and were more often affected by carotid artery atherosclerosis (93.9 % vs
      86.1%; p < 0.002) than non-smoking patients. When analysed for dietary and other
      lifestyle-related risk factors, we found a higher prevalence of carotid
      atherosclerotic disease in patients consuming less than two meals per day than in
      those consuming more than two meals per day (96.6% vs 85.7%; p < 0.001), without
      any significant difference in the mean number of medications taken and in
      specific classes of medications. Total amount of cigarettes smoked, calculated as
      packs per year (39.14 +/- 16.5 vs 20.81 +/- 13.6; p < 0.0001) was higher in
      patients with a diagnosis of atherosclerotic disease of the carotid artery than
      in patients free of this disorder, whereas the average age at which people began
      smoking was lower (17.58 +/- 6.3 vs 21.53 +/- 10.2 years). In a binary model of
      logistic regression adjusted for BMI, HDL-C, smoking status and number of daily
      meals, only smoking status was confirmed to be strongly correlated to clinical
      evidence of carotid atherosclerosis (p < 0.025). CONCLUSIONS: In hypertensive
      patients, in optimal blood pressure control, smoking status has been shown to be
      independently associated with an increased maximum arterial IMT (IMTmax). In
      particular, an increase of the IMT was associated with the total amount of
      cigarettes smoked (calculated as packs per year) and the average age at which
      people began smoking.

PMID- 22867097
TI  - Inhibition of human topoisomerases I and II by simocyclinone D8.
AB  - Simocyclinone D8 is an antibiotic isolated from Streptomyces antibioticus Tu 6040
      that inhibits the supercoiling activity of DNA gyrase. It also exhibits an
      inhibitory effect on human topoisomerase II and an antiproliferative activity
      against some cancer cell lines. Our biochemical studies have revealed that
      simocyclinone D8 can inhibit the catalytic activity of human topoisomerase I.
      Thus, simocyclinone D8 is a dual catalytic inhibitor of human topoisomerases I
      and II.

PMID- 22867098
TI  - The emerging role of histone lysine demethylases in prostate cancer.
AB  - Early prostate cancer (PCa) is generally treatable and associated with good
      prognosis. After a variable time, PCa evolves into a highly metastatic and
      treatment-refractory disease: castration-resistant PCa (CRPC). Currently, few
      prognostic factors are available to predict the emergence of CRPC, and no
      curative option is available. Epigenetic gene regulation has been shown to
      trigger PCa metastasis and androgen-independence. Most epigenetic studies have
      focused on DNA and histone methyltransferases. While DNA methylation leads to
      gene silencing, histone methylation can trigger gene activation or inactivation,
      depending on the target amino acid residues and the extent of methylation (me1,
      me2, or me3). Interestingly, some histone modifiers are essential for PCa tumor
      initiating cell (TIC) self-renewal. TICs are considered the seeds responsible for
      metastatic spreading and androgen-independence. Histone Lysine Demethylases
      (KDMs) are a novel class of epigenetic enzymes which can remove both repressive
      and activating histone marks. KDMs are currently grouped into 7 major classes,
      each one targeting a specific methylation site. Since their discovery, KDM
      expression has been found to be deregulated in several neoplasms. In PCa, KDMs
      may act as either tumor suppressors or oncogenes, depending on their gene
      regulatory function. For example, KDM1A and KDM4C are essential for PCa androgen
      dependent proliferation, while PHF8 is involved in PCa migration and invasion.
      Interestingly, the possibility of pharmacologically targeting KDMs has been
      demonstrated. In the present paper, we summarize the emerging role of KDMs in
      regulating the metastatic potential and androgen-dependence of PCa. In addition,
      we speculate on the possible interaction between KDMs and other epigenetic
      effectors relevant for PCa TICs. Finally, we explore the role of KDMs as novel
      prognostic factors and therapeutic targets. We believe that studies on histone
      demethylation may add a novel perspective in our efforts to prevent and cure
      advanced PCa.

PMID- 22867099
TI  - Is there really a pot of gold at the end of the rainbow? Has the Occupational
      Specific Dispensation, as a mechanism to attract and retain health workers in
      South Africa, leveled the playing field?
AB  - BACKGROUND: South Africa is experiencing a critical shortage of human resources
      for health (HRH) at a time when the population and the burden of ill-health,
      primarily due to HIV, AIDS and TB, are on the increase. This shortage is
      particularly severe within the nursing profession, which has witnessed
      significant emigration due to poor domestic working conditions and remuneration.
      Salaries and other benefits are an obvious pull factor towards foreign countries,
      given the often extreme international wage differentials. The introduction of the
      Occupation Specific Dispensation (OSD) in 2007 sought to improve the public
      services' ability to attract and retain employees thereby reducing incentives to
      emigrate. METHODS: Using a representative basket of commonly bought goods
      (including food, entertainment, fuel and utilities), a purchasing power parity
      (PPP) ratio is an exchange rate between two currencies that equalises the
      international price of buying that basket. Our study makes comparisons, using
      such a PPP index, and allows the identification of real differences in salaries
      for our selected countries (South Africa, United States, United Kingdom, Canada,
      Australia and Saudi Arabia) for the same HRH professions. If PPP adjusted
      earnings are indeed different then this indicates an economic incentive to
      emigrate. RESULTS: Salaries of most South African HRH, particularly registered
      nurses, are dwarfed by their international counterparts (notably United States,
      Canada and Saudi Arabia), although the OSD has gone some way to reduce that
      disparity. All selected foreign countries generally offer higher salaries on a
      PPP adjusted basis. The United Kingdom ($43202) and Australia ($38622), in the
      category of Medical Officer, are the only two examples where the PPP adjustment
      brings the salary below what is being offered in South Africa ($50013 post OSD).
      The PPP adjusted salary differences between registered nurses is very slight for
      South Africa ($18884 post OSD), Australia ($21784) and the United Kingdom
      ($20487). All other foreign countries show large salary advantages across the HRH
      categories examined. CONCLUSION: Whilst South African salaries remain lower than
      their foreign counterparts by and large, the introduction and implementation of
      the OSD has made significant progress in reducing the gap between salaries of HRH
      in South Africa (SA) and the rest of the world. Given that the OSD has narrowed
      the gap between SA and overseas salaries whilst in the context of continued out
      migration of SA HRH, further research into push factors effecting migration needs
      to be undertaken.

PMID- 22867100
TI  - Emergency bedside cesarean delivery: lessons learned in teamwork and patient
      safety.
AB  - BACKGROUND: Maternal cardiovascular and pulmonary events during labor and
      delivery may result in adverse maternal and fetal outcome. Potential etiologies
      include primary cardiac events, pulmonary embolism, eclampsia, maternal
      hemorrhage, and adverse medication events. Remifentanil patient-controlled
      analgesia is an alternative when conventional neuraxial analgesia for labor is
      contraindicated. Although remifentanil is a commonly used analgesic, its use for
      labor analgesia is not clearly defined. CASE PRESENTATION: We present an
      unexpected and unique case of remifentanil toxicity resulting in the need for an
      emergent bedside cesarean delivery. A 30-year-old G3P2 woman receiving
      subcutaneous heparin anticoagulation due to a recent deep vein thrombosis
      developed cardiopulmonary arrest during labor induction due to remifentanil
      toxicity. CONCLUSION: A rapid discussion among the attending obstetric,
      anesthesia, and nursing teams resulted in consensus to perform an emergent
      bedside cesarean delivery resulting in an excellent fetal outcome. During
      maternal cardiopulmonary arrest, a prompt decision to perform a bedside cesarean
      delivery is essential to avoid significant maternal and fetal morbidity. Under
      these conditions, rapid collaboration among obstetric, anesthesia, and nursing
      personnel, and an extensive multi-layered safety process are integral components
      to optimize maternal and fetal outcomes.

PMID- 22867101
TI  - Effects of mixed-method cooling on recovery of medium-fast bowling performance in
      hot conditions on consecutive days.
AB  - This investigation examined physiological and performance effects of cooling on
      recovery of medium-fast bowlers in the heat. Eight, medium-fast bowlers completed
      two randomised trials, involving two sessions completed on consecutive days
      (Session 1: 10-overs and Session 2: 4-overs) in 31 +/- 3 degrees C and 55 +/- 17%
      relative humidity. Recovery interventions were administered for 20 min (mixed
      method cooling vs. control) after Session 1. Measures included bowling
      performance (ball speed, accuracy, run-up speeds), physical demands (global
      positioning system, counter-movement jump), physiological (heart rate, core
      temperature, skin temperature, sweat loss), biochemical (creatine kinase, C
      reactive protein) and perceptual variables (perceived exertion, thermal
      sensation, muscle soreness). Mean ball speed was higher after cooling in Session
      2 (118.9 +/- 8.1 vs. 115.5 +/- 8.6 km . h-1; P = 0.001; d = 0.67), reducing
      declines in ball speed between sessions (0.24 vs. -3.18 km . h-1; P = 0.03; d =
      1.80). Large effects indicated higher accuracy in Session 2 after cooling (46.0
      +/- 11.2 vs. 39.4 +/- 8.6 arbitrary units [AU]; P = 0.13; d = 0.93) without
      affecting total run-up speed (19.0 +/- 3.1 vs. 19.0 +/- 2.5 km . h-1; P = 0.97; d
      = 0.01). Cooling reduced core temperature, skin temperature and thermal sensation
      throughout the intervention (P = 0.001-0.05; d = 1.31-5.78) and attenuated
      creatine kinase (P = 0.04; d = 0.56) and muscle soreness at 24-h (P = 0.03; d =
      2.05). Accordingly, mixed-method cooling can reduce thermal strain after a 10
      over spell and improve markers of muscular damage and discomfort alongside
      maintained medium-fast bowling performance on consecutive days in hot conditions.

PMID- 22867102
TI  - Antioxidants condition pleiotropic vascular responses to exogenous H(2)O(2): role
      of modulation of vascular TP receptors and the heme oxygenase system.
AB  - AIMS: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to
      ascertain the role of redox mechanisms in regulation of vascular tone. Where both
      dilation and constriction have been reported, we examined the hypothesis that the
      ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by
      redox mechanisms and may be modulated by antioxidants. RESULTS: Exogenous
      H(2)O(2) (0.1-10.0 MUM), dose-dependently reduced the internal diameter of rat
      renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was
      obliterated in arteries pretreated with antioxidants, including tempol, pegylated
      superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin
      (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting
      radicals downstream of H(2)O(2), also uncovered vasodilation. INNOVATIONS: Redox
      dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of
      cyclooxygenase (COX) (indomethacin-10 MUM), thromboxane (TP) synthase (CGS13080
      10 MUM), and TP receptor antagonist (SQ29548-1 MUM). However, H(2)O(2) did not
      increase vascular thromboxane B(2) release; instead, it sensitized the
      vasculature to a TP agonist, U46619, an effect reversed by PEG-SOD. Antioxidant
      conditioned dilatory response to H(2)O(2) was accompanied by enhanced vascular
      heme oxygenase (HO)-dependent carbon monoxide generation and was abolished by HO
      inhibitors or by HO-1 & 2 antisense oligodeoxynucleotides treatment of SD rats.
      CONCLUSION: These results demonstrate that H(2)O(2) has antioxidant-modifiable
      pleiotropic vascular effects, where constriction and dilation are brought about
      in the same vascular segment. H(2)O(2)-induced oxidative stress increases
      vascular TP sensitivity and predisposes these arterial segments to constrictor
      prostanoids. Conversely, vasodilation is reliant upon HO-derived products whose
      synthesis is stimulated only in the presence of antioxidants targeting radicals
      downstream of H(2)O(2).

PMID- 22867105
TI  - Concentrations of DDTs and enantiomeric fractions of chiral DDTs in agricultural
      soils from Zhejiang Province, China, and correlations with total organic carbon
      and pH.
AB  - Dichlorodiphenyltrichloroethanes (DDTs) are persistent organic pollutants that
      were widely used in China, especially eastern China, as insecticides. This work
      investigated the concentration, dissipation, and volatilization of DDTs and
      enantiomeric fractions (EFs) of o,p'-DDD and o,p'-DDT in agricultural soils
      collected in 2006 from 58 sites in Zhejiang province. Correlations between DDT
      residues and soil properties were assessed to determine the effect of soil
      properties on the environmental attenuation of DDTs. High concentrations and
      detection frequencies were found for DDTs in agricultural soils in the region
      even though large-scale use of DDTs was banned over 20 years ago. The amount of
      DDTs was about 485 tons in the upper 20 cm of the soil column of cropland in the
      province in 2010, with a dissipation half-life of ~9 years. The mass flux of DDTs
      was 43 ng m(-2) h(-1), which corresponds to emissions of 7.6 tons with an
      emission factor of 1.6% in 2006. The low p,p'-DDT/p,p'-DDE ratios and high o,p'
      DDT/p,p'-DDT ratios suggest that there were no recent inputs of DDTs but fresh
      application of dicofol, which contains DDT (o,p'-DDT in particular) impurities.
      The significant positive correlation between concentrations of DDTs and total
      organic carbon content (TOC) indicates the distribution of DDTs fit a typical
      "secondary distribution" pattern. DEVrac of o,p'-DDD, which is defined as the
      absolute value of EFs subtracted from 0.5, was significantly related with most of
      the physicochemical and microbial soil properties. The most significant
      correlation is that between DEVrac of o,p'-DDD and soil pH (p < 0.001),
      indicating that the soil pH plays a key role in enantioselective residues of
      DDTs.

PMID- 22867103
TI  - Employment of tandem mass spectrometry for the accurate and specific
      identification of oligosaccharide structures.
AB  - A method is described for the rapid identification of oligosaccharides employing
      a library of tandem MS spectra. Identification is aided by software that compares
      the sample tandem MS to those in the library. The method incorporates quadrupole
      time-of-flight mass spectrometry along with an annotated oligosaccharide (OS)
      structure library and the MassHunter Personal Compound Database and Library
      (PCDL) software. With an automated spectra search, OS structures in different
      samples are readily identified. This method is shown to be useful in the study of
      milk oligosaccharides but can be readily applied to oligosaccharide pools in
      other biological tissues.

PMID- 22867106
TI  - The Inter-Organizational Summit on Education and Training (ISET) 2010 survey on
      the influence of the Houston Conference training guidelines.
AB  - A conference specific to the education and training of clinical neuropsychology
      was held in 1997, which led to a report published in the Archives of Clinical
      Neuropsychology (Hannay, J., Bieliauskas, L., Crosson, B., Hammeke, T., Hamsher,
      K., & Koffler, S. (1998).   Proceedings of the Houston Conference on Specialty
      Education and Training in Clinical Neuropsychology. Archives of Clinical
      Neuropsychology, 13, 157-250.). The guidelines produced by this conference have
      been referred to as the Houston Conference (HC) guidelines. Since that time,
      there has been considerable discussion, and some disagreement, about whether the
      HC guidelines produced a positive outcome in the training of neuropsychologists.
      To explore this question and determine how widely the HC guidelines were
      implemented, a meeting was held in 2006. Present and past leaders of the American
      Psychological Association Division 40 (Clinical Neuropsychology), the National
      Academy of Neuropsychology, and the Association of Postdoctoral Programs in
      Clinical Neuropsychology met to discuss the possible need for an Inter
      Organizational Summit on Education and Training (ISET). A decision was reached to
      have the ISET Steering Committee conduct a survey of clinical neuropsychologists
      that could address the extent to which HC guidelines were present in the
      specialty and whether the influence of the HC guidelines was positive. An online
      survey was constructed, with data gathered in 2010. The current paper presents
      and discusses the ISET survey results. Specific findings need to be viewed
      cautiously due to the relatively low response rate. However, with some direct
      parallels to a larger recent survey of clinical neuropsychologists, the following
      general conclusions appear well founded: (a) the demographics of respondents in
      the ISET survey are comparable with a recent larger professional practice survey
      and thus may reasonably represent the specialty; (b) the HC guidelines appear to
      have been widely adopted by training programs, in that a large proportion of
      younger practitioners endorsed having had HC-adherent training; and (c) HC
      adherent training is associated with a higher frequency endorsement of being well
      prepared to engage in key professional activities subsequent to the completion of
      training when compared with those not having HC-adherent training. Overall, the
      ISET Steering Committee has concluded that the HC guidelines have been widely
      adopted and that trainees associate participation in HC-adherent training as
      advantageous. A potential revision based on unfavorable outcomes is deemed
      unnecessary. Nonetheless, the ISET Steering Committee recognizes that training
      needs change as a function of the broadening of our field and the introduction of
      related new technologies, which may prompt updates. The ISET Steering Committee
      supports the idea that periodic review and updating of training models may be is
      prudent.

PMID- 22867107
TI  - Barriers and facilitators to implementing Decision Boxes in primary healthcare
      teams to facilitate shared decisionmaking: a study protocol.
AB  - BACKGROUND: Decision Boxes are summaries of the most important benefits and harms
      of health interventions provided to clinicians before they meet the patient, to
      prepare them to help patients make informed and value-based decisions. Our
      objective is to explore the barriers and facilitators to using Decision Boxes in
      clinical practice, more precisely factors stemming from (1) the Decision Boxes
      themselves, (2) the primary healthcare team (PHT), and (3) the primary care
      practice environment. METHODS/DESIGN: A two-phase mixed methods study will be
      conducted. Eight Decision Boxes relevant to primary care, and written in both
      English and in French, will be hosted on a website together with a tutorial to
      introduce the Decision Box. The Decision Boxes will be delivered as weekly emails
      over a span of eight weeks to clinicians of PHTs (family physicians, residents
      and nurses) in five primary care clinics located across two Canadian provinces.
      Using a web-questionnaire, clinicians will rate each Decision Box with the
      Information Assessment Method (cognitive impacts, relevance, usefulness, expected
      benefits) and with a questionnaire based on the Theory of Planned Behavior to
      study the determinants of clinicians' intention to use what they learned from
      that Decision Box in their patient encounter (attitude, social norm, perceived
      behavioral control). Web-log data will be used to monitor clinicians' access to
      the website. Following the 8-week intervention, we will conduct semi-structured
      group interviews with clinicians and individual interviews with clinic
      administrators to explore contextual factors influencing the use of the Decision
      Boxes. Data collected from questionnaires, focus groups and individual interviews
      will be combined to identify factors potentially influencing implementation of
      Decision Boxes in clinical practice by clinicians of PHTs. CONCLUSIONS: This
      project will allow tailoring of Decision Boxes and their delivery to overcome the
      specific barriers identified by clinicians of PHTs to improve the implementation
      of shared decision making in this setting.

PMID- 22867108
TI  - Observation of the binary coalescence and equilibration of micrometer-sized
      droplets of aqueous aerosol in a single-beam gradient-force optical trap.
AB  - The binary coalescence of aqueous droplets has been observed in a single-beam
      gradient-force optical trap. By measuring the time-dependent intensity for
      elastic scattering of light from the trapping laser, the dynamics of binary
      coalescence have been examined and the time scale for equilibration of a
      composite droplet to ambient conditions has been determined. These data are
      required for modeling the agglomeration of aqueous droplets in dense sprays and
      atmospheric aerosol. Elastic-light scattering from optically trapped particles
      has not been used previously to study the time-resolved dynamics of mixing. It is
      shown to offer a unique opportunity to characterize the binary coalescence of
      aqueous droplets with radii from 1 to 6 MUm. The study of this size regime, which
      cannot be achieved by conventional imaging methods, is critical for understanding
      the interactions of droplets in the environment of dense sprays.

PMID- 22867109
TI  - Soluble Zintl phases A14ZnGe16 (A = K, Rb) featuring [(eta3-Ge4)Zn(eta2-Ge4)]6-
      and [Ge4]4- clusters and the isolation of [(MesCu)2(eta3,eta3-Ge4)]4-: the
      missing link in the solution chemistry of tetrahedral group 14 element Zintl
      clusters.
AB  - The number of Zintl phases containing polyhedral clusters of tetrel elements that
      are accessible for chemical reactions of the main-group element clusters is
      rather limited. The synthesis and structural characterization of two novel
      ternary intermetallic phases A(14)ZnGe(16) (A = K, Rb) are presented, and their
      chemical reactivity is investigated. The compounds can be rationalized as Zintl
      phases with 14 alkali metal cations A(+) (A = K, Rb), two tetrahedral [Ge(4)](4-)
      Zintl anions, and one anionic heterometallic [(Ge(4))Zn(Ge(4))](6-) cluster per
      formula unit. The Zn-Ge cluster comprises two (Ge(4)) tetrahedra which are linked
      by a Zn atom, with one (Ge(4)) tetrahedron coordinating with a triangular face
      (eta(3)) and the other one with an edge (eta(2)). [(eta(3)-Ge(4))Zn(eta(2)
      Ge(4))](6-) is a new isomer of the [(Ge(4))Zn(Ge(4))](6-) anion in Cs(6)ZnGe(8).
      The phases dissolve in liquid ammonia and thus represent rare examples of soluble
      Zintl compounds with deltahedral units of group 14 element atoms. Compounds with
      tetrahedral [E(4)](4-) species have previously been isolated from solution for E
      = Si, Sn, and Pb, and the current investigation provides the "missing link" for E
      = Ge. Reaction of an ammonia solution of K(14)ZnGe(16) with MesCu (Mes = 2,4,6
      (CH(3))(3)C(6)H(2)) in the presence of [18]-crown-6 (1,4,7,10,13,16
      hexaoxacyclooctadecane) yielded crystals of the salt [K([18]-crown
      6)](2)K(2)[(MesCu)(2)Ge(4)](NH(3))(7.5) with the polyanion [(MesCu)(2)Ge(4)](4-).
      This MesCu-stabilized tetrahedral [Ge(4)](4-) cluster also completes the series
      of [(MesCu)(2)Si(4-x)Ge(x)](4-) clusters, which have previously been isolated
      from solution for x = 0 and 0.7, as the end member with x = 4. The electronic
      structures of [(Ge(4))Zn(Ge(4))](6-) and [(MesCu)(2)Ge(4)](4-) were investigated
      in terms of a molecular orbital description and analyses of the electron
      localization functions. The results are compared with band structure calculations
      for the A(14)ZnGe(16) phases (A = K, Rb).

PMID- 22867110
TI  - Preparation of hemispherical polymer particles by cleavage of a Janus poly(methyl
      methacrylate)/polystyrene composite particle.
AB  - Micrometer-sized, hemispherical particles were successfully prepared as a result
      of the cleavage of Janus PMMA/PS composite particles by dispersion into
      acetone/water (9/1-10/0 v/v) media or a THF/water (8/2 v/v) medium. The spherical
      composite particles having a Janus structure were prepared by the slow
      evaporation of toluene from homogeneous PMMA/PS/toluene droplets dispersed in an
      aqueous medium in advance. It was clarified that the difference in affinity
      between PMMA and PS phases with respect to the media caused the cleavage of the
      composite particles. This method is expected to be a novel approach to the
      preparation of nonspherical polymer particles.

PMID- 22867111
TI  - Vitamin D supplementation in the management of knee osteoarthritis: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Osteoarthritis (OA) is a common health issue worldwide in the aging
      population who are also commonly deficient in vitamin D. Our previous study
      suggested that higher serum 25-(OH)D levels were associated with reduced knee
      cartilage loss, implying that vitamin D supplementation may prevent the
      progression of knee OA. The aim of the VItamin D Effects on OA (VIDEO) study is
      to compare, over a 2- year period, the effects of vitamin D supplementation
      versus placebo on knee structural changes, knee pain, and lower limb muscle
      strength in patients with symptomatic knee OA. METHODS/DESIGN: Randomised,
      placebo-controlled, and double-blind clinical trial aiming to recruit 400
      subjects (200 from Tasmania and 200 from Victoria) with both symptomatic knee OA
      and vitamin D deficiency (serum [25-(OH)D] level of >12.5 nmol/liter and <60
      nmol/liter). Participants will be randomly allocated to vitamin D supplementation
      (50,000 IU compounded vitamin D3 capsule monthly) or identical inert placebo
      group for 2 years. The primary endpoint is loss of knee cartilage volume measured
      by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities
      Index of OA (WOMAC) knee pain score. The secondary endpoints will be other knee
      structural changes, and lower limb muscle strength. Several other outcome
      measures including core muscle images and central blood pressure will be
      recorded. Linear and logistic regression will be used to compare changes between
      groups using univariable and multivariable modeling analyses. Both intention to
      treat and per protocol analyses will be utilized. DISCUSSION: The trial is
      designed to test if vitamin D supplementation will reduce loss of knee cartilage
      volume, prevent the progression of other knee structural abnormalities, reduce
      knee pain and strengthen lower limb muscle strength, thus modify disease
      progression in knee OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01176344; Australian New Zealand Clinical Trials Registry:
      ACTRN12610000495022.

PMID- 22867112
TI  - Could albumin level explain the higher mortality in hemodialysis patients with
      pulmonary hypertension?
AB  - BACKGROUND: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is
      still unclear. The aim of this study was to identify the risk factors associated
      with the presence of PH in chronic hemodialysis patients and to verify whether
      these factors might explain the highest mortality among them. METHODS: We
      conducted a retrospective study of hemodialysis patients who started treatment
      from August 2001 to October 2007 and were followed up until April 2011 in a
      Brazilian referral medical school. According to the results of echocardiography
      examination, patients were allocated in two groups: those with PH and those
      without PH. Clinical parameters, site and type of vascular access, bioimpedance,
      and laboratorial findings were compared between the groups and a logistic
      regression model was elaborated. Actuarial survival curves were constructed and
      hazard risk to death was evaluated by Cox regression analysis. RESULTS: PH > 35
      mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in
      extracellular water, ventricular thickness, left atrium diameter, and ventricular
      filling. In a univariate analysis, extracellular water was associated with PH
      (relative risk = 1.194; 95% CI of 1.006 - 1.416; p = 0.042); nevertheless, in a
      multiple model, only left atrium enlargement was independently associated with PH
      (relative risk =1.172; 95% CI of 1.010 - 1.359; p = 0.036). PH (hazard risk =
      3.008; 95% CI of 1.285 - 7.043; p = 0.011) and age (hazard risk of 1.034 per year
      of age; 95% CI of 1.000 - 7.068; p = 0.047) were significantly associated with
      mortality in a multiple Cox regression analysis. However, when albumin was taken
      in account the only statistically significant association was between albumin
      level and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 - 0.984; p =
      0.047) while the presence of PH lost its statistical significance (p = 0.184).
      Mortality was higher in patients with PH (47.8% vs 25%) who also had a
      statistically worse survival after the sixth year of follow up. CONCLUSIONS: PH
      in hemodialysis patients is associated with parameters of volume overload that
      sheds light on its pathophysiology. Mortality is higher in hemodialysis patients
      with PH and the low albumin level can explain this association.

PMID- 22867113
TI  - Copolymerization of cyclohexene oxide and CO2 with a chromium diamine
      bis(phenolate) catalyst.
AB  - A diamine-bis(phenolate) chromium(III) complex, {CrCl[O(2)NN'](BuBu)}(2)
      catalyzes the copolymerization of cyclohexene oxide with carbon dioxide. The
      synthesis of this metal complex is straightforward, and it can be obtained in
      high yields. This catalyst incorporates a tripodal amine-bis(phenolate) ligand,
      which differs from the salen or salan ligands typically used with Cr and Co
      complexes that have been employed as catalysts for the synthesis of such
      polycarbonates. The catalyst reported herein yields low molecular weight polymers
      with narrow polydispersities. Structural and spectroscopic details of this
      complex along with its copolymerization activity for cyclohexene oxide and carbon
      dioxide are presented.

PMID- 22867114
TI  - Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat
      hepatocytes.
AB  - The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats,
      single doses cause centrolobular necrosis accompanied by increases in plasma
      transaminases and bilirubin. To elicit these effects, TA requires oxidative
      bioactivation, leading first to its S-oxide (TASO) and then to its chemically
      reactive S,S-dioxide (TASO(2)), which ultimately modifies amine-lipids and
      proteins. To generate a suite of liver proteins adducted by TA metabolites for
      proteomic analysis and to reduce the need for both animals and labeled compounds,
      we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic
      at concentrations up to 50 mM for 40 h. On the other hand, TASO was highly toxic
      to isolated hepatocytes as indicated by LDH release, cellular morphology, and
      vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially
      blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole and was
      strongly inhibited by TA. Significantly, we found that hepatocytes produce TA
      from TASO relatively efficiently by back-reduction. The covalent binding of
      [(14)C]-TASO is inhibited by unlabeled TA, which acts as a "cold-trap" for
      [(14)C]-TA and prevents its reoxidation to [(14)C]-TASO. This in turn increases
      the net consumption of [(14)C]-TASO despite the fact that its oxidation to
      TASO(2) is inhibited. The potent inhibition of TASO oxidation by TA, coupled with
      the back-reduction of TASO and its futile redox cycling with TA, may help explain
      phenomena previously interpreted as "saturation toxicokinetics" in the in vivo
      metabolism and toxicity of TA and TASO. The improved understanding of the
      metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes
      to prepare protein adducts for target protein identification.

PMID- 22867115
TI  - Adolescent girls' friendship networks, body dissatisfaction, and disordered
      eating: examining selection and socialization processes.
AB  - Previous research has shown that adolescent girls tend to resemble their friends
      in their level of body dissatisfaction and disordered eating. However, no studies
      to date have attempted to disentangle the underlying peer selection and
      socialization processes that may explain this homophily. The current study used
      longitudinal stochastic actor-based modeling to simultaneously examine these two
      processes in a large community sample of adolescent girls (N = 1,197) from nine
      Australian girls' high schools. Friendship nominations and measures of body
      dissatisfaction, dieting and bulimic behaviors were collected across three annual
      waves. Results indicated that selection rather than socialization effects
      contributed to similarity within friendship groups when both processes were
      examined simultaneously. Specifically, girls tended to select friends who were
      similar to themselves in terms of body dissatisfaction and bulimic behaviors, but
      dissimilar in terms of dieting. Network and individual attribute variables also
      emerged as significant in explaining changes in adolescents' friendships and
      behaviors. As well as having important clinical implications, the findings point
      to the importance of controlling for friendship selection when examining the role
      of peers in adolescent body image and eating problems.

PMID- 22867116
TI  - Effects of rumination on child and adolescent depressive reactions to a natural
      disaster: the 2010 Nashville flood.
AB  - The current longitudinal study tested hypotheses about Nolen-Hoeksema's (1987,
      1991) response styles theory (RST) of depression in a sample of child and
      adolescent public school students. Wave 1 measures of rumination, distraction,
      and depression were obtained 6 months prior to the 2010 Nashville flood. Similar
      measures plus a measure of flood-related stressors were administered at Wave 2,
      approximately ten days after students returned to school after the flood. Results
      revealed an indirect effect of preflood rumination on postflood depressive
      symptoms via the intervening variable of postflood rumination, and partial
      mediation of the effect of preflood depression on postflood depression. Further,
      the interaction of rumination with flood-related stressors was moderated by age,
      suggesting that rumination may not become a strong cognitive diathesis for
      depression until adolescence. Developmental implications emerged for the
      treatment of child and adolescent victims of natural disasters and for the
      application of RST to children and adolescents.

PMID- 22867117
TI  - Attentional biases and the persistence of sad mood in major depressive disorder.
AB  - This study examined whether attentional biases for emotional information are
      associated with impaired mood recovery following a sad mood induction among
      individuals with and without major depressive disorder (MDD). Attentional biases
      were assessed with an exogenous cuing task using emotional facial expressions as
      cues among adults with (n = 48) and without (n = 224) current MDD. Mood
      reactivity and recovery were measured following a sad mood induction. Mood
      reactivity strongly predicted mood recovery; however, this relationship was
      moderated by attentional biases for negative emotional stimuli. Biases for sad
      and fear stimuli were associated with diminished mood recovery following mood
      induction across the sample. However, biases for sad stimuli were associated with
      significantly greater impairments in mood recovery among individuals with MDD
      than healthy controls. Furthermore, within the MDD group, impaired mood recovery
      was positively associated with depression severity. These results suggest that
      attentional biases maintain depression, in part, by facilitating the persistence
      of sad mood.

PMID- 22867118
TI  - An examination of the triarchic conceptualization of psychopathy in incarcerated
      and nonincarcerated samples.
AB  - The current study tested hypotheses associated with the triarchic
      conceptualization of psychopathy (Patrick, 2010b; Patrick, Fowles, & Krueger,
      2009), which describes three distinctive, albeit related, phenotypic domains
      boldness, meanness, and disinhibition. We used two samples consisting of 209
      female prison inmates and 627 undergraduate students whom had been administered a
      range of psychopathy and psychopathy-relevant measures. Our results indicated
      that the triarchic domains explained variance in other psychopathy models to
      degrees consistent with conceptual expectations. We also examined associations
      between the triarchic domains and personality traits relevant to psychopathy in
      the female correctional sample. The results showed that boldness was
      preferentially associated with narcissism, thrill/adventure seeking, and low
      behavioral inhibition system functioning; meanness with machiavellianism, low
      empathy, and low behavioral inhibition system; and disinhibition with impulsivity
      and fun seeking.

PMID- 22867119
TI  - Antiviral and immunological effects of tenofovir microbicide in vaginal herpes
      simplex virus 2 infection.
AB  - The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1
      acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%.
      We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse
      vaginal challenge model. In vitro plaque assays and luminex multiplex bead
      analysis were used, respectively, to measure postinfection vaginal viral shedding
      (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2
      properties, we evaluated the direct antiviral effect of TFV and the oral prodrug
      tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated
      mice, TFV-treated mice had significantly lower clinical scores, developed later
      genital lesions, and showed reduced vaginal viral shedding. Furthermore, the
      levels of IFN-gamma, IL-2, TNF-alpha, and other cytokines were altered in the
      vaginal fluid following topical tenofovir treatment and subsequent HSV-2
      challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in
      vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed
      that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal
      challenge model. Therefore, this model would be suitable for evaluating present
      and future microbicide candidates. Furthermore, the present study warrants
      further investigation of TDF in microbicides.

PMID- 22867120
TI  - Telepsychology outcome research with children and adolescents: a review of the
      literature.
AB  - Using technology as a service medium has been touted as a potentially feasible
      and effective alternative and/or adjunct to in-person services. The
      telepsychology literature has given less attention to children and adolescents in
      comparison to adults. This review provides a summary and critique of the
      empirical research focused on psychological services provided to children and
      adolescents using three technology media (i.e., videoconferencing, Internet, and
      telephone). The evidentiary support for providing services with each of these
      media for a range of concerns is encouraging. The quantity and quality of
      research, however, both need to be enhanced to better understand how technology
      mediates the provision of youth services, as well as to elevate telepsychology
      within professional psychology. Future research and its subsequent impact on
      policy and practice are considered.

PMID- 22867121
TI  - Telemedicine and adherence to national guidelines for ADHD evaluation: a case
      study.
AB  - The pilot project evaluated a telemedicine clinic's adherence to American Academy
      of Pediatrics (AAP) guidelines for attention-deficit/hyperactivity disorder
      (ADHD) evaluation. Real-time videoconferencing linked the patients, the families,
      and the specialty mental health team. The ADHD Telemedicine Clinic adherence to
      AAP guidelines was tracked using chart data. The study included 22 patients (Mean
      age = 9.3 years, SD = 2.3 years) participating in 69 telemedicine visits across
      13 different school-related sites. The ADHD Telemedicine Clinic reached extremely
      high adherence rates across the AAP evaluation guidelines for ADHD, ranging from
      95-100% across the six guidelines. No factor inherent to the telemedicine service
      delivery mechanism impeded adherence to national guidelines for ADHD evaluation.
      Telemedicine-based outreach had the greatest impact on AAP Guideline #4, stating
      that information should be obtained from the child's academic setting. The school
      based telemedicine clinic allowed increased communication across the school and
      specialty mental health systems and facilitated greater input across child,
      parent, school personnel, and mental health professionals.

PMID- 22867123
TI  - Perceptions of virtual reality among therapists who do not apply this technology
      in clinical practice.
AB  - Research has documented the usefulness of virtual reality (VR) in treating a
      number of psychopathologies. Despite its recognized clinical utility, VR remains
      underutilized in clinical practice. For the purpose of this study, 262 therapists
      who reported that they did not currently use VR in psychotherapy were surveyed
      about their perceptions of the use of this technology in clinical practice.
      Results suggest that reluctance in using this technology stems from beliefs about
      the required training, equipment, and financial costs and from unfamiliarity with
      the various benefits and applications of VR. The significance of promoting
      greater use of this new technology is discussed.

PMID- 22867122
TI  - Telemedicine-based alcohol services for rural offenders.
AB  - Research has consistently shown that alcohol use is a problem in rural
      communities and access to substance abuse treatment, particularly evidence-based
      treatment is limited. Because telemedicine has been shown to be effective in
      delivering services, this article presents a novel and innovative way of using
      telemedicine technology in the form of videoconferencing to deliver an evidence
      based alcohol intervention (motivational enhancement therapy) with at-risk
      alcohol users in real-world settings (rural probation and parole offices). This
      article focuses on: (a) creating a profile of an at-risk group of rural alcohol
      users; (b) describing the evidence-based intervention; and (c) describing the
      innovative telemedicine-based service delivery approach.

PMID- 22867124
TI  - Providers' voices on telebehavioral health: survey of an outpatient counseling
      agency in Alaska.
AB  - Hope Counseling Center sought to expand behavioral health services to underserved
      populations in Alaska by offering telebehavioral health services. Providers
      completed a questionnaire addressing their experiences, opinions, and training
      needs as they relate to telebehavioral health. Open conversations about the
      training needs, limitations, and benefits of telebehavioral health supported
      program development and led to training on new equipment, rapport building, and
      telebehavioral health outcome studies.

PMID- 22867125
TI  - Telepsychiatry services at a tribally run behavioral health clinic.
AB  - Telepsychiatry provides a helpful resource to rural, poor, and isolated
      communities for whom traditional psychiatry may not be an option. Focusing on a
      tribally run behavioral health clinic, this article describes the clinic's
      transition from traditional psychiatry to telepsychiatry and then delineates
      benefits and challenges of telepsychiatry in this setting. Telepsychiatry is
      recommended based on the experiences of this clinic serving a large southwestern
      Native American community.

PMID- 22867126
TI  - Telehealth for underserved families: an evidence-based parenting program.
AB  - Families with a child diagnosed with attention-deficit hyperactivity disorder
      completed an 8-session parenting program, the Group Triple P Positive Parenting
      Program, provided by videoconferencing technology. Families reported improved
      child behavior (effect size of d = -1.23) and decreased parent distress (d = 
      0.34). Parent training implemented with videoconferencing technology can be an
      effective way of delivering evidence-based services to families with specialized
      needs.

PMID- 22867127
TI  - Sport psychology group consultation using social networking web sites.
AB  - A social networking Web site, Facebook, was used to deliver long-term sport
      psychology consultation services to student-athletes (i.e., soccer players) in 30
      to 60-min weekly sessions. Additional short-term team building, group cohesion,
      communication, anger management, injury rehabilitation, mental toughness,
      commitment, and leadership workshops were provided. Cohesion and overall
      relationships between both the student-athletes and the sport psychology
      consultants benefited from this process. Social networking Web sites offer a
      practical way of providing sport psychology consulting services that does not
      require use of major resources.

PMID- 22867128
TI  - Antihyperglycemic and hypolipidemic effects of alpha, beta-amyrin, a triterpenoid
      mixture from Protium heptaphyllum in mice.
AB  - BACKGROUND: Pentacyclic triterpenes in general exert beneficial effects in
      metabolic disorders. This study investigated the effects of alpha, beta-amyrin, a
      pentacyclic triterpene mixture from the resin of Protium heptaphyllum on blood
      sugar level and lipid profile in normal and streptozotocin (STZ)-induced diabetic
      mice, and in mice fed on a high-fat diet (HFD). FINDINGS: Mice treated with
      alpha, beta-amyrin (10, 30 and 100 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.)
      had significantly reduced STZ-induced increases in blood glucose (BG), total
      cholesterol (TC) and serum triglycerides (TGs). Unlike glibenclamide that showed
      significant reductions in BG, TC and TGs in normoglycemic mice, alpha, beta
      amyrin did not lower normal blood sugar levels but at 100 mg/kg, manifested a
      hypolipidemic effect. Also, alpha, beta-amyrin effectively reduced the elevated
      plasma glucose levels during the oral glucose tolerance test. Moreover, the
      plasma insulin level and histopathological analysis of pancreas revealed the
      beneficial effect of alpha, beta-amyrin in the preservation of beta cell
      integrity. In mice treated orally with alpha, beta-amyrin (10, 30 and 100 mg/kg)
      or fenofibrate (200 mg/kg), the HFD-associated rise in serum TC and TGs were
      significantly less. The hypocholesterolemic effect of alpha, beta-amyrin appeared
      more prominent at 100 mg/kg with significant decreases in VLDL and LDL
      cholesterol and an elevation of HDL cholesterol. Besides, the atherogenic index
      was significantly reduced by alpha, beta-amyrin. CONCLUSIONS: These findings
      reflect the potential antihyperglycemic and hypolipidemic effects of alpha, beta
      amyrin mixture and suggest that it could be a lead compound for drug development
      effective in diabetes and atherosclerosis.

PMID- 22867130
TI  - Processes of change in CBT of adolescent depression: review and recommendations.
AB  - A growing body of research supports the efficacy of cognitive-behavioral therapy
      (CBT) for adolescent depression. The mechanisms through which CBT exerts its
      beneficial effects on adolescent patients suffering from depression, however,
      remain unclear. The current article reviews the CBT for adolescent depression
      process literature. Our review focuses on several process variables: the
      therapeutic alliance, patient cognitive change, and therapist adherence to, and
      competence in, the theory-specified techniques of therapy. Given that the vast
      majority of CBT process research has been conducted in the context of adult
      psychotherapy, we also review relevant adult research as a framework for
      understanding adolescent process research and to inform future investigations.
      Methodological issues are addressed and recommendations for future process
      research are raised.

PMID- 22867129
TI  - Tobacco sales in pharmacies: a survey of attitudes, knowledge and beliefs of
      pharmacists employed in student experiential and other worksites in Western New
      York.
AB  - BACKGROUND: Pharmacies are venues in which patients seek out products and
      professional advice in order to improve overall health. However, many pharmacies
      in the United States continue to sell tobacco products, which are widely known to
      cause detrimental health effects. This conflict presents a challenge to
      pharmacists, who are becoming increasingly more involved in patient health
      promotion activities. This study sought to assess Western New York (WNY) area
      pharmacists' opinions about the sale of tobacco products in pharmacies, and
      pharmacists' opinions on their role in patient smoking cessation. METHODS:
      Participants responded to two parallel surveys; a web-based survey was completed
      by 148 university-affiliated pharmacist preceptors via a list based sample, and a
      mail-based survey was completed by the supervising pharmacist in 120 area
      pharmacies via a list-based sample. The combined response rate for both surveys
      was 31%. Univariate and bivariate analyses were performed to determine any
      significant differences between the preceptor and supervising pharmacist survey
      groups. RESULTS: Over 75% of respondents support legislation banning the sale of
      tobacco products in pharmacies. Over 86% of respondents would prefer to work in a
      pharmacy that does not sell tobacco products. Differences between preceptor and
      supervising pharmacist groups were observed. Action regarding counseling patients
      was uncommon among both groups. CONCLUSIONS: Pharmacists support initiatives that
      increase their role in cessation counseling and initiatives that restrict the
      sale of tobacco products in pharmacies. These data could have important
      implications for communities and pharmacy practice.

PMID- 22867131
TI  - New insights into the regulation of neutrophil NADPH oxidase activity in the
      phagosome: a focus on the role of lipid and Ca(2+) signaling.
AB  - SIGNIFICANCE: Reactive oxygen species, produced by the phagosomal NADPH oxidase
      of neutrophils, play a significant physiological role during normal defense.
      Their role is not only to kill invading pathogens, but also to act as modulators
      of global physiological functions of phagosomes. Given the importance of NADPH
      oxidase in the immune system, its activity has to be decisively controlled by
      distinctive mechanisms to ensure appropriate regulation at the phagosome. RECENT
      ADVANCES: Here, we describe the signal transduction pathways that regulate
      phagosomal NADPH oxidase in neutrophils, with an emphasis on the role of lipid
      metabolism and intracellular Ca(2+) mobilization. CRITICAL ISSUES: The potential
      involvement of Ca(2+)-binding S100A8 and S100A9 proteins, known to interact with
      the plasma membrane NADPH oxidase, is also considered. FUTURE DIRECTIONS: Recent
      technical progress in advanced live imaging microscopy will permit to focus more
      accurately on phagosomal rather than plasma membrane NADPH oxidase regulation
      during neutrophil phagocytosis.

PMID- 22867133
TI  - Physicochemical modification of kafirin microparticles and their ability to bind
      bone morphogenetic protein-2 (BMP-2), for application as a biomaterial.
AB  - Vacuolated spherical kafirin microparticles with a mean diameter of 5 MUm can be
      formed from an acidic solution with water addition. Three-dimensional scaffolds
      for hard tissue repair require large structures with a high degree of
      interconnected porosity. Cross-linking the formed kafirin microparticles using
      wet heat or glutaraldehyde treatment resulted in larger structures (approximately
      20 MUm), which, while similar in size and external morphology, were apparently
      formed by further assisted assembly by two significantly different mechanisms.
      Heat treatment, which increased the vacuole size, involved kafirin polymerization
      by disulfide bonding with the microparticles being formed from round, coalesced
      nanostructures, as shown by atomic force microscopy (AFM). Kafirin polymerization
      of glutaraldehyde-treated microparticles was not by disulfide bonding, and the
      nanostructures, as revealed by AFM, were spindle shaped. Both treatments enhanced
      BMP-2 binding to the microparticles, probably due to their increased size. Thus,
      these modified kafirin microparticles have potential as natural, nonanimal
      protein bioactive scaffolds. 

PMID- 22867132
TI  - Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs
      in adolescent male rat substantia nigra.
AB  - BACKGROUND: Increased risk of schizophrenia in adolescent males indicates that a
      link between the development of dopamine-related psychopathology and testosterone
      driven brain changes may exist. However, contradictions as to whether
      testosterone increases or decreases dopamine neurotransmission are found and most
      studies address this in adult animals. Testosterone-dependent actions in neurons
      are direct via activation of androgen receptors (AR) or indirect by conversion to
      17beta-estradiol and activation of estrogen receptors (ER). How midbrain dopamine
      neurons respond to sex steroids depends on the presence of sex steroid
      receptor(s) and the level of steroid conversion enzymes (aromatase and 5alpha
      reductase). We investigated whether gonadectomy and sex steroid replacement could
      influence dopamine levels by changing tyrosine hydroxylase (TH) protein and mRNA
      and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase
      (COMT) and monoamine oxygenase (MAO) A and B] in the adolescent male rat
      substantia nigra. We hypothesized that adolescent testosterone would regulate sex
      steroid signaling through regulation of ER and AR mRNAs and through modulation of
      aromatase and 5alpha-reductase mRNA levels. RESULTS: We find ERalpha and AR in
      midbrain dopamine neurons in adolescent male rats, indicating that dopamine
      neurons are poised to respond to circulating sex steroids. We report that
      androgens (T and DHT) increase TH protein and increase COMT, MAOA and MAOB mRNAs
      in the adolescent male rat substantia nigra. We report that all three sex
      steroids increase AR mRNA. Differential action on ER pathways, with ERalpha mRNA
      down-regulation and ERbeta mRNA up-regulation by testosterone was found. 5alpha
      reductase-1 mRNA was increased by AR activation, and aromatase mRNA was decreased
      by gonadectomy. CONCLUSIONS: We conclude that increased testosterone at
      adolescence can shift the balance of sex steroid signaling to favor androgenic
      responses through promoting conversion of T to DHT and increasing AR mRNA.
      Further, testosterone may increase local dopamine synthesis and metabolism,
      thereby changing dopamine regulation within the substantia nigra. We show that
      testosterone action through both AR and ERs modulates synthesis of sex steroid
      receptor by altering AR and ER mRNA levels in normal adolescent male substantia
      nigra. Increased sex steroids in the brain at adolescence may alter substantia
      nigra dopamine pathways, increasing vulnerability for the development of
      psychopathology.

PMID- 22867134
TI  - The effect of comparative context on evaluative conditioning.
AB  - Evaluative conditioning (EC) is a change in the evaluation of a stimulus after
      the stimulus co-occurred with affective stimuli. The present research examined
      whether EC of one stimulus depends also on the co-occurrence of another stimulus
      with positive or negative stimuli. We paired two target people with affective
      stimuli. We found that a person who appeared eight times with positive stimuli
      and eight times with negative stimuli was liked more when the other person
      appeared always (16 times) with negative stimuli than when the other person
      appeared always with positive stimuli. The manipulation did not change the US
      evaluation or the general standard on the value dimension of what a positive or
      negative stimulus is. We suggest that like other evaluative traits (e.g., evil,
      pretty) co-occurrence with affective stimuli is sensitive to temporary standards.
      The manipulation changed the standard of what co-occurrence with affective
      stimuli is considered positive versus negative.

PMID- 22867264
TI  - Detection of biomarkers for hepatocellular carcinoma using a hybrid univariate
      gene selection methods.
AB  - BACKGROUND: Discovering new biomarkers has a great role in improving early
      diagnosis of Hepatocellular carcinoma (HCC). The experimental determination of
      biomarkers needs a lot of time and money. This motivates this work to use in
      silico prediction of biomarkers to reduce the number of experiments required for
      detecting new ones. This is achieved by extracting the most representative genes
      in microarrays of HCC. RESULTS: In this work, we provide a method for extracting
      the differential expressed genes, up regulated ones, that can be considered
      candidate biomarkers in high throughput microarrays of HCC. We examine the power
      of several gene selection methods (such as Pearson's correlation coefficient,
      Cosine coefficient, Euclidean distance, Mutual information and Entropy with
      different estimators) in selecting informative genes. A biological interpretation
      of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and
      Genomes) pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and
      Integrated Discovery) databases. The top ten genes selected using Pearson's
      correlation coefficient and Cosine coefficient contained six genes that have been
      implicated in cancer (often multiple cancers) genesis in previous studies. A
      fewer number of genes were obtained by the other methods (4 genes using Mutual
      information, 3 genes using Euclidean distance and only one gene using Entropy). A
      better result was obtained by the utilization of a hybrid approach based on
      intersecting the highly ranked genes in the output of all investigated methods.
      This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in
      different types of cancer) in the top ten genes of the list of intersected genes.
      CONCLUSIONS: To strengthen the effectiveness of the univariate selection methods,
      we propose a hybrid approach by intersecting several of these methods in a
      cascaded manner. This approach surpasses all of univariate selection methods when
      used individually according to biological interpretation and the examination of
      gene expression signal profiles.

PMID- 22867265
TI  - Application of symmetry-adapted perturbation theory to small ionic systems.
AB  - The application of symmetry-adapted perturbation theory (SAPT) to small ionic
      systems was investigated in the context of the accuracy of calculated interaction
      energies for alkali halides. Two forms of alkali halides were considered: ion
      pairs M(+)X(-) (M = Li, Na, K, Rb, and X = F, Cl, Br, I) and dimers (MX)(2). The
      influence of the order of energy correction terms included in SAPT and the effect
      of the so-called hybrid approach to SAPT on the accuracy of the calculated
      energies (such as the interaction energies in the ion pairs and the binding
      energies in the dimers with respect to two free monomers) were studied. The
      effects of the size of basis sets, combined with SAPT, on the accuracy were also
      established.

PMID- 22867266
TI  - Effect of positioning on the accuracy of decision making of association football
      top-class referees and assistant referees during competitive matches.
AB  - The aim of this study was to examine the effect of positioning on the correctness
      of decision making of top-class referees and assistant referees during
      international games. Match analyses were carried out during the Federation
      Internationale de Football Association (FIFA) Confederations Cup 2009 and 380
      foul play incidents and 165 offside situations were examined. The error
      percentage for the referees when indicating the incidents averaged 14%. The
      lowest error percentage occurred in the central area of the field, where the
      collaboration of the assistant referee is limited, and was achieved when
      indicating the incidents from a distance of 11-15 m, whereas this percentage
      peaked (23%) in the last 15-min match period. The error rate for the assistant
      referees was 13%. Distance of the assistant referee to the offside line did not
      have an impact on the quality of the offside decision. The risk of making
      incorrect decisions was reduced when the assistant referees viewed the offside
      situations from an angle between 46 and 60 degrees . Incorrect offside decisions
      occurred twice as often in the second as in the first half of the games.
      Perceptual-cognitive training sessions specific to the requirements of the game
      should be implemented in the weekly schedule of football officials to reduce the
      overall error rate.

PMID- 22867267
TI  - Simultaneous measurement of mechanical and surface properties in
      thermoresponsive, anchored hydrogel films.
AB  - Hydrogel films have been used extensively in the preparation of biosensors and
      biomedical devices. The characteristics of the aqueous interface of the polymer
      layer are significant for the biosensor or device function; likewise, the
      changing mechanical properties of thermoresponsive polymers are an important
      feature that affects the polymer behavior. Atomic force microscopy was used here
      to characterize both the surface and the mechanical properties of polymeric
      hydrogel films prepared from a thermoresponsive terpolymer of N
      isopropylacrylamide and acrylic acid with benzophenonemethacrylate as a
      photoreactive cross-linker comonomer. The force-distance curves thus obtained
      were analyzed to assess both the surface forces and the mechanical response that
      were associated with the hydrogel. These properties were investigated as a
      function of temperature, in water and in Tris buffer, for different degrees of
      polymer cross-linking. For samples in water, the distance over which the surface
      forces were effective was found to remain constant as the temperature was
      increased from 26 to 42  degrees C, even though the mechanical response indicated
      that the samples had been heated past the lower critical solution temperature, or
      LCST. The bulk of the polymer becomes less soluble above the LCST, although this
      does not seem to affect the surface properties. This may be due to the
      segregation of the acrylic acid-rich polymer segments near the gel surface, which
      is in agreement with reports for related systems.

PMID- 22867268
TI  - Chemical synthesis and immunological evaluation of the inner core oligosaccharide
      of Francisella tularensis.
AB  - Francisella tularensis, which is a Gram negative bacterium that causes tularemia,
      has been classified by the Center for Disease Control and Prevention (CDC) as a
      category A bioweapon. The development of vaccines, immunotherapeutics, and
      diagnostics for F. tularensis requires a detailed knowledge of the saccharide
      structures that can be recognized by protective antibodies. We have synthesized
      the inner core region of the lipopolysaccharide (LPS) of F. tularensis to probe
      antigenic responses elicited by a live and subunit vaccine. The successful
      preparation of the target compound relied on the use of a disaccharide which was
      modified by the orthogonal protecting groups diethylisopropylsilyl (DEIPS), 2
      naphthylmethyl (Nap), allyl ether (All), and levulinoyl (Lev) ester. The ability
      to remove the protecting groups in different orders made it possible to establish
      the optimal glycosylations sequence to prepare a highly crowded 1,2,3-cis
      configured branching point. A variety of different methods were exploited to
      control anomeric selectivities of the glycosylations. A comparison of the (1)H
      NMR spectra of isolated material and the synthetic derivative confirmed the
      reported structural assignment of the inner core oligosaccharide of F. tularensis
      . The observation that immunizations with LPS lead to antibody responses to the
      inner core saccharides provides an impetus to further explore this compound as a
      vaccine candidate.

PMID- 22867269
TI  - Statistical process control for data without inherent order.
AB  - BACKGROUND: The XmR chart is a powerful analytical tool in statistical process
      control (SPC) for detecting special causes of variation in a measure of quality.
      In this analysis a statistic called the average moving range is used as a measure
      of dispersion of the data. This approach is correct for data with natural
      underlying order, such as time series data. There is however conflict in the
      literature over the appropriateness of the XmR chart to analyse data without an
      inherent ordering. METHODS: We derive the maxima and minima for the average
      moving range in data without inherent ordering, and show how to calculate this
      for any data set. We permute a real world data set and calculate control limits
      based on these extrema. RESULTS: In the real world data set, permuting the order
      of the data affected an absolute difference of 109 percent in the width of the
      control limits. DISCUSSION: We prove quantitatively that XmR chart analysis is
      problematic for data without an inherent ordering, and using real-world data,
      demonstrate the problem this causes for calculating control limits. The resulting
      ambiguity in the analysis renders it unacceptable as an approach to making
      decisions based on data without inherent order. CONCLUSION: The XmR chart should
      only be used for data endowed with an inherent ordering, such as a time series.
      To detect special causes of variation in data without an inherent ordering we
      suggest that one of the many well-established approaches to outlier analysis
      should be adopted. Furthermore we recommend that in all SPC analyses authors
      should consistently report the type of control chart used, including the measure
      of variation used in calculating control limits.

PMID- 22867270
TI  - Unexpected recovery from longterm renal failure in severe diffuse proliferative
      lupus nephritis.
AB  - BACKGROUND: Severe renal manifestation of systemic lupus erythematosus (SLE) is
      not uncommon and is associated with an indeterminate prognosis. Complete
      remission can be obtained, however, at least in the young when chronic lesions
      are absent and adequate anti-inflammatory therapy is immediately initiated. CASE
      PRESENTATION: We report the unusual case of a 12-year-old girl who presented with
      severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy
      revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN)
      with cellular crescents in 15 out of 18 glomeruli and full-house pattern in
      immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A)
      according to ISN/RPS classification. The serological parameters confirmed the
      diagnosis of SLE and the patient was immediately treated with methylprednisolone,
      cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of
      her general condition, no substantial improvement of renal function could be
      achieved and the patient needed hemodialysis treatment for 12 weeks.
      Unexpectedly, in the further follow-up at first diuresis increased and thereafter
      also creatinine levels substantially declined so that hemodialysis could be
      discontinued. Today, 6 years after the initial presentation, the patient has
      normal renal function and a SLEDAI score of 0 under a continuous
      immunosuppressive therapy with Mycophenolate mofetil (MMF) and low dose steroid.
      CONCLUSION: Despite the severity of the initial renal injury and the unfavourable
      renal prognosis the kidney apparently has a tremendous capacity to recover in
      young patients when the damage is acute and adequate anti-inflammatory therapy is
      initiated without delay.

PMID- 22867271
TI  - Vaginal gel formulation based on theaflavin derivatives as a microbicide to
      prevent HIV sexual transmission.
AB  - We previously demonstrated that a commercially available natural product
      preparation with high content (>90%) of theaflavin derivatives (TFmix) exhibited
      potent anti-HIV activities. Here we developed a TFmix gel formulation as a
      topical microbicide candidate. The effect of TFmix on the amyloid fibril
      formation of semen-derived enhancer of virus infection (SEVI) peptide was
      detected by transmission electron microscopy. The toxicity of the TFmix gel was
      evaluated using human vaginal and cervical epithelial cell lines and rabbit
      vaginal irritation models, respectively. Levels of proinflammatory cytokines (IL
      1beta, IL-6, IL-8, and TNF-alpha) and immunoregulatory cytokines (IL-10 and GM
      CSF) in cervicovaginal lavages (CVLs) were measured by ELISA kits. Proliferating
      cell nuclear antigen (PCNA) immunostaining was performed to evaluate inflammation
      in the vaginal tissues. TFmix gel could degrade SEVI-specific amyloid fibrils and
      showed low cytotoxicity to epithelial cells of the female reproductive tract. No
      apparent cervicovaginal toxicity was observed at any time point evaluated
      following the intravaginal administration of TFmix gel to rabbits, whereas
      application of N-9 gel resulted in damage to the vaginal epithelium. Neither
      proinflammatory nor immunoregulatory cytokine production was triggered by TFmix
      gel. Only low expression of PCNA was observed in vaginal tissues of TFmix gel
      treated rabbits. The concentration of TFmix in plasma was very low (below the
      lower limit of quantitation) 1 h after a single vaginal administration of TFmix
      gel. However, TFmix was still detected in the cervicovaginal lavages (CVLs) 6 h
      after treatment, indicating that it could be retained in the vaginal cavity for a
      long period of time. With its potent anti-HIV-1 activity, marked stability at
      acidic condition, low mucosal toxicity, and lack of systemic absorption, TFmix
      gel can be considered as an inexpensive and safe microbicide candidate for the
      prevention of HIV sexual transmission.

PMID- 22867272
TI  - Alteration in plasma protein binding properties of propranolol and flurbiprofen
      during development of adjuvant-induced arthritis in rats.
AB  - Adjuvant-induced arthritis (AA) in the rat is used as a model for rheumatoid
      arthritis. In AA rats, the pharmacokinetics of various drugs is affected due to
      the alterations of plasma protein binding of drugs. We choose propranolol (PL)
      and flurbiprofen (FP) as model basic and acidic drugs, respectively, and
      investigated the effect of AA induction on their plasma protein binding at each
      developing stage of inflammation. The plasma protein binding of PL and FP was
      dramatically changed due to reduced albumin and increased alpha1-acid
      glycoprotein levels for at least 21 days after adjuvant treatment. Moreover, we
      illustrated the differences in protein binding in AA between both the drugs in
      each developing stage of inflammation. These results suggest that the changed
      plasma protein levels in AA rats accompanying the altered protein binding of
      drugs affect the pharmacokinetics of drugs which extensively bind to plasma
      protein under inflammatory condition.

PMID- 22867273
TI  - Absorption of TAK-491, a new angiotensin II receptor antagonist, in animals.
AB  - The absorption process in animals of TAK-491, designed as ester-based prodrug
      with medoxomil moiety, was evaluated. In the plasma of rats and dogs, TAK-536,
      the pharmacologically active metabolite, was present as the main component with
      hardly detectable concentrations of TAK-491 after oral administration of TAK-491.
      In the rat portal plasma, TAK-536 was also present as the main component with
      hardly detectable concentrations of TAK-491 after jejunal loop injection of TAK
      491, suggesting TAK-491 was absorbed from small intestine and hydrolyzed almost
      completely during absorption. Caco-2 study indicated the permeability of TAK-491
      was improved by prodrug modification and the compound could be mainly transferred
      as TAK-491. This is well consistent with the facts that the AUC and T(max) of TAK
      536 after oral administration of TAK-491 were higher and shorter than those after
      oral administration of TAK-536 in dogs Hydrolysis of TAK-491 is observed not only
      by the intestinal and hepatic S9 fraction, but also by plasma and human serum
      albumin. However, medoxomil alcohol wasn't detected during the hydrolysis of TAK
      491. These metabolic features of TAK-491 were similar to olmesartan medoxomil,
      suggesting the hydrolytic pathway and enzymes for TAK-491 when catalyzing to TAK
      536 would be the same as olmesartan medoxomil.

PMID- 22867274
TI  - Metabolic profiling of TRPV1 antagonists of the benzothiazole amide series:
      implications for in vitro genotoxicity assessment.
AB  - In vitro metabolic profiling and in vitro genotoxicity assessment are important
      aspects of the drug discovery program as they eliminate harmful compounds from
      further development. In standard in vitro genotoxicity testing, induced rat liver
      S9 is used as an exogenous bio-activation system for detecting promutagens. In
      this study we show that rat liver S9 is an insufficient system regarding the
      conversion of TRPV1 antagonists of the benzothiazole amide series into relevant
      in vivo metabolites. Human and rat hepatocyte experiments demonstrated generation
      of an aryl amine metabolite that was subsequently N-acetylated. The hydrolyzed
      metabolites as well as the parent compound were also metabolized into glutathione
      (GSH) conjugates. Rat liver S9 exhibited a very low amide hydrolysis capacity and
      no formation of GSH conjugates when supplemented with NADPH and GSH. The
      discrepancy in metabolic capability between hepatocytes and rat liver S9 led to
      confounding results in in vitro genotoxicity assessment for this chemical class
      as judged by the results of Ames test, mouse lymphoma assay, SOS/umu test and
      Comet assay in rat hepatocytes. This study highlights the pivotal role that
      understanding the mechanism of metabolite formation has in interpreting as well
      as designing reliable and relevant in vitro genotoxicity experiments.

PMID- 22867275
TI  - Genetic predisposition, parity, age at first childbirth and risk for breast
      cancer.
AB  - BACKGROUND: Recent studies have identified several single-nucleotide
      polymorphisms (SNPs) associated with the risk of breast cancer and parity and age
      at first childbirth are well established and important risk factors for breast
      cancer. The aim of the present study was to examine the interaction between these
      environmental factors and genetic variants on breast cancer risk. METHODS: The
      Malmo Diet and Cancer Study (MDCS) included 17 035 female participants, from
      which 728 incident breast cancer cases were matched to 1448 controls. The
      associations between 14 SNPs and breast cancer risk were investigated in
      different strata of parity and age at first childbirth. A logistic regression
      analysis for the per allele risk, adjusted for potential confounders yielded odds
      ratios (OR) with 95% confidence intervals (CI). RESULTS: Six of the previously
      identified SNPs showed a statistically significant association with breast cancer
      risk: rs2981582 (FGFR2), rs3803662 (TNRC9), rs12443621 (TNRC9), rs889312
      (MAP3K1), rs3817198 (LSP1) and rs2107425 (H19). We could not find any
      statistically significant interaction between the effects of tested SNPs and
      parity/age at first childbirth on breast cancer risk after adjusting for multiple
      comparisons. CONCLUSIONS: The results of this study are in agreement with
      previous studies of null interactions between tested SNPs and parity/age at first
      childbirth with regard to breast cancer risk.

PMID- 22867276
TI  - The impact of immigration and vaccination in reducing the incidence of hepatitis
      B in Catalonia (Spain).
AB  - BACKGROUND: The Hepatitis B virus (HBV) infection is a major cause of liver
      disease and liver cancer worldwide according to the World Health Organization.
      Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of
      infected infants become chronic carriers and have an increased risk of cirrhosis
      and primary hepatocellular carcinoma. The aim of this study was to investigate
      the relationship between the reduction in acute hepatitis B incidence and the
      universal vaccination programme in preadolescents in Catalonia (Spain), taking
      population changes into account, and to construct a model to forecast the future
      incidence of cases that permits the best preventive strategy to be adopted.
      METHODS: Reported acute hepatitis B incidence in Catalonia according to age,
      gender, vaccination coverage, percentage of immigrants and the year of report of
      cases was analysed. A statistical analysis was made using three models:
      generalized linear models (GLM) with Poisson or negative binomial distribution
      and a generalized additive model (GAM). RESULTS: The higher the vaccination
      coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups
      with vaccination coverage > 70%, the reduction in incidence was 2-fold higher
      than in groups with a coverage <70% (p <0.01). The increase in incidence was
      significantly-higher in groups with a high percentage of immigrants and more than
      15% (p <0.01) in immigrant males of working age (19-49 years). CONCLUSIONS: The
      results of the adjusted models in this study confirm that the global incidence of
      hepatitis B has declined in Catalonia after the introduction of the universal
      preadolescent vaccination programme, but the incidence increased in male
      immigrants of working age. Given the potential severity of hepatitis B for the
      health of individuals and for the community, universal vaccination programmes
      should continue and programmes in risk groups, especially immigrants, should be
      strengthened.

PMID- 22867277
TI  - Comparison between integrated backscatter intravascular ultrasound and 64-slice
      multi-detector row computed tomography for tissue characterization and volumetric
      assessment of coronary plaques.
AB  - BACKGROUND: The purpose of this study was to determine the cut-off values of
      Hounsfield units (HU) for the discrimination of plaque components and to evaluate
      the feasibility of measurement of the volume of plaque components using multi
      detector row computed tomography (MDCT). METHODS: Coronary lesions (125 lesions
      in 125 patients) were visualized by both integrated backscatter intravascular
      ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used
      as a gold standard to determine the cut off values of HU for the discrimination
      of plaque components. RESULTS: Plaques were classified as lipid pool (n =50),
      fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool,
      fibrosis and calcification were 18 +/- 18 HU (-19 to 58 HU), 95 +/- 24 HU (46 to
      154 HU) and 378 +/- 99 HU (188 to 605 HU), respectively. Using receiver operating
      characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values
      to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was
      correlated with that measured by IB-IVUS (r =0.66, p <0.001), whereas fibrous
      volume was not (r =0.21, p =0.059). CONCLUSION: Lipid volume measured by MDCT was
      moderately correlated with that measured by IB-IVUS. MDCT may be useful for
      volumetric assessment of the lipid volume of coronary plaques, whereas the
      assessment of fibrosis volume was unstable.

PMID- 22867278
TI  - Developing core outcome sets for clinical trials: issues to consider.
AB  - The selection of appropriate outcomes or domains is crucial when designing
      clinical trials in order to compare directly the effects of different
      interventions in ways that minimize bias. If the findings are to influence policy
      and practice then the chosen outcomes need to be relevant and important to key
      stakeholders including patients and the public, health care professionals and
      others making decisions about health care. There is a growing recognition that
      insufficient attention has been paid to the outcomes measured in clinical trials.
      These issues could be addressed through the development and use of an agreed
      standardized collection of outcomes, known as a core outcome set, which should be
      measured and reported, as a minimum, in all trials for a specific clinical area.
      Accumulating work in this area has identified the need for general guidance on
      the development of core outcome sets. Key issues to consider in the development
      of a core outcome set include its scope, the stakeholder groups to involve,
      choice of consensus method and the achievement of a consensus.

PMID- 22867279
TI  - Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular
      system.
AB  - SIGNIFICANCE: Oxidants were once principally considered perpetrators of injury
      and disease. However, this has become an antiquated view, with cumulative
      evidence showing that the oxidant hydrogen peroxide serves as a signaling
      molecule. Hydrogen peroxide carries vital information about the redox state of
      the cell and is crucial for homeostatic regulation during health and adaptation
      to stress. RECENT ADVANCES: In this review, we examine the contemporary concepts
      for how hydrogen peroxide is sensed and transduced into a biological response by
      introducing post-translational oxidative modifications on select proteins.
      Oxidant sensing and signaling by kinases are of particular importance as they
      integrate oxidant signals into phospho-regulated pathways. We focus on CAMKII,
      PKA, and PKG, kinases whose redox regulation has notable impact on cardiovascular
      function. CRITICAL ISSUES: In addition, we examine the mechanism for regulating
      intracellular hydrogen peroxide, considering the net concentrations that may
      accumulate. The effects of endogenously generated oxidants are often modeled by
      applying exogenous hydrogen peroxide to cells or tissues. Here we consider
      whether model systems exposed to exogenous hydrogen peroxide have relevance to
      systems where the oxidant is generated endogenously, and if so, what
      concentration can be justified in terms of relevance to health and disease.
      FUTURE DIRECTIONS: Improving our understanding of hydrogen peroxide signaling and
      the sensor proteins that it can modify will help us develop new strategies to
      regulate intracellular signaling to prevent disease.

PMID- 22867281
TI  - Association of blood glucose levels with in-hospital mortality and 30-day
      readmission in patients undergoing invasive cardiovascular surgery.
AB  - OBJECTIVE: This study aimed to evaluate the association of mean and maximum blood
      glucose (BG) levels with in-hospital mortality and 30-day hospital readmission
      among patients in the intensive care unit (ICU) undergoing invasive
      cardiovascular (CV) surgery. RESEARCH DESIGN AND METHODS: The retrospective
      database analysis consisted of data from 3132 patients from 17 hospitals who
      underwent an invasive CV surgery during 1/2000-12/2006. Patients with
      hyperglycemia were identified based on serum BG levels recorded from 12 hours
      prior to and 24 hours after ICU admission. Separate logistic regression models
      were used to examine the association of mean and maximum BG levels to in-hospital
      mortality and 30-day readmission, adjusting for patient demographics,
      comorbidities and laboratory values. RESULTS: The adjusted odds ratio (OR) for in
      hospital mortality was 1.07 (95% CI: 1.01-1.12; p < .001) for every 0.56-mmol/L
      increase in mean BG, and OR = 1.06 (95% CI: 1.03-1.08, p < .001) for every 0.56
      mmol/L increase in maximum BG. Mean BG was not associated with 30-day readmission
      while maximum BG had a borderline association: OR = 1.02 (95% CI: 1.00-1.03, p =
      .06). LIMITATION: The results are not generalizable to all cardiovascular
      surgical patients since only those undergoing invasive procedures were included
      in the study. CONCLUSIONS: Higher mean and maximum BG levels were associated with
      increased risk of in-hospital mortality but not with 30-day readmission. Further
      research is needed to identify optimal BG targets and the effects of avoiding
      extreme hyperglycemia on patient outcomes.

PMID- 22867280
TI  - Interpersonal stress generation as a mechanism linking rumination to
      internalizing symptoms in early adolescents.
AB  - Rumination is a risk factor for depressive and anxiety symptoms in adolescents.
      Previous investigations of the mechanisms linking rumination to internalizing
      problems have focused primarily on cognitive factors. We investigated whether
      interpersonal stress generation plays a role in the longitudinal relationship
      between rumination and internalizing symptoms in young adolescents. Adolescents
      (Grades 6-8, N = 1,065) from an ethnically diverse community completed measures
      of depressive and anxiety symptoms, perceived friendship quality, and peer
      victimization at two assessments, 7 months apart. We determined whether
      rumination predicted increased exposure to peer victimization and whether changes
      in perceived friendship quality mediated this relationship. We also evaluated
      whether peer victimization mediated the association between rumination and
      internalizing symptoms. Adolescents who engaged in high levels of rumination at
      baseline were more likely to experience overt, relational, and reputational
      victimization at a subsequent time point 7 months later, controlling for baseline
      internalizing symptoms and victimization. Increased communication with peers was
      a significant partial mediator of this association for relational (z = 1.98, p =
      .048) and reputational (z = 2.52, p = .024) victimization. Exposure to overt (z =
      3.37, p = .014), relational (z = 3.67, p < .001), and reputational (z = 3.78, p <
      .001) victimization fully mediated the association between baseline rumination
      and increases in internalizing symptoms over the study period. These findings
      suggest that interpersonal stress generation is a mechanism linking rumination to
      internalizing problems in adolescents and highlight the importance of targeting
      interpersonal factors in treatment and preventive interventions for adolescents
      who engage in rumination.

PMID- 22867292
TI  - Ring-opening polymerization of epoxides catalyzed by uranyl complexes: an
      experimental and theoretical study of the reaction mechanism.
AB  - A comprehensive computational study on the ring-opening polymerization of
      propylene oxide catalyzed by uranyl chloride [UO(2)Cl(2)(THF)(3)] and the uranyl
      aryloxide [UO(2)(OAr)(2)(THF)(2)] (Ar = 2,6-(t)Bu(2)C(6)H(3)) is reported. The
      initiation and propagation steps have been probed and significant differences
      between the two catalysts discovered. The initiation step involving uranyl
      chloride is an intermolecular process because the orientation of the lone pair on
      the initiating chloride nucleophile is optimally oriented toward the empty sigma*
      antibonding orbital of the epoxide, which lowers the activation barrier by 22
      kcal mol(-1). Thus, initiation is orbitally controlled. Propagation occurs
      through a dimeric species, and low-temperature fluorescence spectroscopy has been
      used to probe this experimentally. In contrast the initiation step for the uranyl
      aryloxide catalyzed mechanism is intramolecular because of the steric constraints
      imposed by the bulky substituents on the aryl ring and the fact that the lone
      pair on the nucleophile is able to approach the propylene oxide coordinated to
      the same uranium center. Thus, initiation is principally sterically controlled.
      Propagation is, however, intermolecular, and this can be traced to steric
      effects. Experimental evidence in the form of fluorescence spectroscopy and
      diffusion NMR has been used to explore the propagation process in solution.

PMID- 22867293
TI  - The general alcoholics anonymous tools of recovery: the adoption of 12-step
      practices and beliefs.
AB  - Working the 12 steps is widely prescribed for Alcoholics Anonymous (AA) members
      although the relative merits of different methods for measuring step work have
      received minimal attention and even less is known about how step work predicts
      later substance use. The current study (1) compared endorsements of step work on
      an face-valid or direct measure, the Alcoholics Anonymous Inventory (AAI), with
      an indirect measure of step work, the General Alcoholics Anonymous Tools of
      Recovery (GAATOR); (2) evaluated the underlying factor structure of the GAATOR
      and changes in step work over time; (3) examined changes in the endorsement of
      step work over time; and (4) investigated how, if at all, 12-step work predicted
      later substance use. New AA affiliates (N = 130) completed assessments at intake,
      3, 6, and 9 months. Significantly more participants endorsed step work on the
      GAATOR than on the AAI for nine of the 12 steps. An exploratory factor analysis
      revealed a two-factor structure for the GAATOR comprising behavioral step work
      and spiritual step work. Behavioral step work did not change over time, but was
      predicted by having a sponsor, while Spiritual step work decreased over time and
      increases were predicted by attending 12-step meetings or treatment. Behavioral
      step work did not prospectively predict substance use. In contrast, spiritual
      step work predicted percent days abstinent. Behavioral step work and spiritual
      step work appear to be conceptually distinct components of step work that have
      distinct predictors and unique impacts on outcomes.

PMID- 22867294
TI  - Racial/ethnic differences in the influence of cultural values, alcohol resistance
      self-efficacy, and alcohol expectancies on risk for alcohol initiation.
AB  - Prior research has reported racial/ethnic differences in the early initiation of
      alcohol use, suggesting that cultural values that are central to specific
      racial/ethnic groups may be influencing these differences. This 1-year
      longitudinal study examines associations between two types of cultural values,
      parental respect (honor for one's parents) and familism (connectedness with
      family), both measured at baseline, and subsequent alcohol initiation in a sample
      of 6,054 (approximately 49% male, 57% Hispanic, 22% Asian, 18% non-Hispanic
      White, and 4% non-Hispanic Black) middle school students in Southern California.
      We tested whether the associations of cultural values with alcohol initiation
      could be explained by baseline measures of alcohol resistance self-efficacy (RSE)
      and alcohol expectancies. We also explored whether these pathways differed by
      race/ethnicity. In the full sample, adolescents with higher parental respect were
      less likely to initiate alcohol use, an association that was partially explained
      by higher RSE and fewer positive alcohol expectancies. Familism was not
      significantly related to alcohol initiation. Comparing racial/ethnic groups,
      higher parental respect was protective against alcohol initiation for Whites and
      Asians, but not Blacks or Hispanics. There were no racial/ethnic differences in
      the association between familism and alcohol initiation. Results suggest that
      cultural values are important factors in the decision to use alcohol and these
      values appear to operate in part, by influencing alcohol positive expectancies
      and RSE. Interventions that focus on maintaining strong cultural values and
      building strong bonds between adolescents and their families may help reduce the
      risk of alcohol initiation.

PMID- 22867295
TI  - A comparison of four telephone-based counseling styles for recovering stimulant
      users.
AB  - The continuing development and refinement of empirically supported interventions
      to increase participation in posttreatment care and promote sustained abstinence
      from illicit drug use is a priority for the addictions field. The purpose of this
      study was to assess the combined and relative effectiveness of four types of
      counseling styles, delivered by telephone, relative to a no call control
      condition. Stimulant users (N = 302) were randomized to one of four low-cost,
      telephone support protocols (unstructured/nondirective, unstructured/directive,
      structured/nondirective, structured/directive) or a standard referral to
      aftercare without telephone counseling (control). All of the study participants
      were nearing the completion of (or had completed) an intensive phase of
      structured, outpatient stimulant abuse treatment. Drug use and aftercare
      participation were assessed at 3 and 12 months following randomization. Intent-to
      treat analyses showed no significant time-by-group interactions for these primary
      outcomes. Subsequent analyses, however, revealed a significant difference between
      the aggregated call groups and the control group at the time of the 3-month
      follow-up. The mean ASI drug use severity composite score for subjects in the
      call conditions declining from .058 at baseline to .048 at 3 months, whereas the
      no call/control group average score increased from .053 to .062 (chi (1) = 4.95,
      p = .026). A similar-and slightly stronger-effect was found when the study sample
      was restricted to those reporting any use during the month prior to the baseline
      interview (n = 152). This study provides modest support for the telephone-based
      counseling approaches strategies examined in this project. Subsequent research
      will assess interactions between patient characteristics and counseling styles,
      and improved identification of which treatment graduates might be more likely to
      benefit from this type of continuing support. (PsycINFO Database Record (c) 2013
      APA, all rights reserved).

PMID- 22867296
TI  - How well do TTM measures work among a sample of individuals with unhealthy
      alcohol use that is characterized by low readiness to change?
AB  - Little is known about the applicability of the transtheoretical model of
      intentional behavior change (TTM) to individuals with unhealthy alcohol use that
      is primarily characterized by low readiness to change. This study examined the
      psychometric properties of short measures by assessing three core constructs of
      the TTM: the 20-item Processes of Change (POC-20) scale, and short versions of
      the Alcohol Decisional Balance Scale (ADBS) and the Alcohol Abstinence Self
      Efficacy (AASE) scale. A sample of 427 individuals with unhealthy alcohol use
      (Mage = 30 years, 65% men), identified at job agencies in northeastern Germany,
      completed all three scales. Item difficulty (d), selectivity (rit), and
      Cronbach's alpha were calculated. Confirmatory factory analyses were used to test
      for construct validity and latent mean differences across the stages. The
      psychometric properties of the 8-item AASE were adequate (d range: 0.59-0.78; rit
      range: 0.59-0.68; alpha range: 0.74-0.81), except for one subscale. Most items of
      the POC-20 and the 10-item ADBS were difficult (dPOC range: 0.08-0.40; dADBS
      range: 0.21-0.58); selectivity (ritPOC range: 0.26-0.62; ritADBS range: 0.34
      0.68) and internal consistency (alphaPOC range: 0.41-0.76; alphaADBS range: 0.64
      0.78) were low to moderate. Construct validity was acceptable (Comparative Fit
      Index range: 0.95-0.99). The association between stages and TTM constructs
      partially followed expected patterns. Suggestions for modifications of TTM
      measures are discussed for better applicability among proactively recruited
      samples of individuals with unhealthy alcohol use and with primarily low
      readiness to change. (PsycINFO Database Record (c) 2013 APA, all rights
      reserved). 

PMID- 22867297
TI  - The interaction of nicotine withdrawal and panic disorder in the prediction of
      panic-relevant responding to a biological challenge.
AB  - The current investigation evaluated nicotine withdrawal symptoms elicited by 12
      hours of smoking deprivation on anxious and fearful responding to bodily
      sensations among daily smokers with and without panic disorder (PD). It was
      hypothesized that smokers with PD who were experiencing greater levels of
      nicotine withdrawal would experience the greatest levels of fearful responding
      to, and delayed recovery from, a 10% carbon dioxide-enriched air (CO2) biological
      challenge procedure. Participants were 58 adults who reported smoking 19.72
      cigarettes daily (SD = 7.99). Results indicated that nicotine withdrawal and PD
      status interacted to predict greater postchallenge panic attack symptoms. Also,
      individuals with PD initially evidenced a quicker decrease in subjective anxiety
      following the challenge, but their rate of recovery decelerated over time as
      compared to those without PD. There was, however, no significant interaction for
      change in subjective anxiety pre- to postchallenge. Results are discussed in
      relation to the role of nicotine withdrawal in anxious and fearful responding for
      smokers with PD.

PMID- 22867298
TI  - Human Immunodeficiency Virus Gag and protease: partners in resistance.
AB  - Human Immunodeficiency Virus (HIV) maturation plays an essential role in the
      viral life cycle by enabling the generation of mature infectious virus particles
      through proteolytic processing of the viral Gag and GagPol precursor proteins. An
      impaired polyprotein processing results in the production of non-infectious virus
      particles. Consequently, particle maturation is an excellent drug target as
      exemplified by inhibitors specifically targeting the viral protease (protease
      inhibitors; PIs) and the experimental class of maturation inhibitors that target
      the precursor Gag and GagPol polyproteins. Considering the different target sites
      of the two drug classes, direct cross-resistance may seem unlikely. However,
      coevolution of protease and its substrate Gag during PI exposure has been
      observed both in vivo and in vitro. This review addresses in detail all mutations
      in Gag that are selected under PI pressure. We evaluate how polymorphisms and
      mutations in Gag affect PI therapy, an aspect of PI resistance that is currently
      not included in standard genotypic PI resistance testing. In addition, we
      consider the consequences of Gag mutations for the development and positioning of
      future maturation inhibitors.

PMID- 22867422
TI  - Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat
      through down regulation of inflammatory response.
AB  - BACKGROUND: The importance of doxorubicin (Dox), as a potent antitumor
      antibiotic, is limited by the development of life-threatening cardiomyopathy. It
      has been shown that free radicals are involved in acute doxorubicin-induced
      toxicity. The aim of this study was to determine the protective effect of vitamin
      E and telmisartan in acute doxorubicin induced cardiotoxicity. METHODS: Thirty
      two male Sprague - Dawley rats were involved in this study and were randomly
      separated into 4 groups, eight rats in each group, one group received normal
      saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the
      other two groups also received doxorubicin 20 mg/kg I.P as single dose after
      seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan
      (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and
      analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting
      assay for ICAM-1, while left ventricular function was analyzed by microcatheter,
      also estimated the level of oxidative stress parameters (MDA and Catalase) and
      cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and
      after treatment period by 48 hours. RESULTS: The immunofluorescent staining
      showed that administration of vitamin E and telmisartan are attenuated of
      mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level
      of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there
      is marked reduction of myocardial troponin-I levels with improved LV function in
      vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA,
      LDH, CK-MB levels significantly (P < 0.01), and were counteracted by
      administration of vitamin E and telmisartan, but did not significantly affect
      serum catalase activity. CONCLUSIONS: Antioxidant effect (vitamin E and
      telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.

PMID- 22867423
TI  - Immunomodulatory properties of the protein fraction from Phorphyra columbina.
AB  - The phycobiliproteins from  Rhodophyta , R-phycoerythrin (R-PE) and C-phycocyanin
      (C-PC), have been shown to exert immunomodulatory effects. This study evaluated
      the effects of a  Phorphyra columbina  protein fraction (PF) and R-PE and C-PC on
      rat primary splenocytes, macrophages, and T-lymphocytes in vitro. PF featured
      various protein species, including R-PE and C-PC. PF showed mitogenic effects on
      rat splenocytes and was nontoxic to cells except at 1 g L(-1) protein. IL-10
      secretion was enhanced by PF in rat splenocytes, macrophages, and especially T
      lymphocytes, whereas it was markedly diminished by R-PE and C-PC. The production
      of pro-inflammatory cytokines by macrophages was inhibited. The effect of PF on
      IL-10 was evoked by JNK/p38 MAPK and NF-kappaB-dependent pathways in macrophages
      and T-lymphocytes. It was concluded that PF has immunomodulatory effects on
      macrophages and lymphocytes that appear to be predominantly anti-inflammatory via
      up-regulated IL-10 production and cannot be accounted for by R-PE and C-PC.

PMID- 22867425
TI  - Role of mixed boundaries on flow in open capillary channels with curved air-water
      interfaces.
AB  - Flow in unsaturated porous media or in engineered microfluidic systems is
      dominated by capillary and viscous forces. Consequently, flow regimes may differ
      markedly from conventional flows, reflecting strong interfacial influences on
      small bodies of flowing liquids. In this work, we visualized liquid transport
      patterns in open capillary channels with a range of opening sizes from 0.6 to 5.0
      mm using laser scanning confocal microscopy combined with fluorescent latex
      particles (1.0 MUm) as tracers at a mean velocity of ~0.50 mm s(-1). The observed
      velocity profiles indicate limited mobility at the air-water interface. The
      application of the Stokes equation with mixed boundary conditions (i.e., no slip
      on the channel walls and partial slip or shear stress at the air-water interface)
      clearly illustrates the increasing importance of interfacial shear stress with
      decreasing channel size. Interfacial shear stress emerges from the velocity
      gradient from the adjoining no-slip walls to the center where flow is trapped in
      a region in which capillary forces dominate. In addition, the increased
      contribution of capillary forces (relative to viscous forces) to flow on the
      microscale leads to increased interfacial curvature, which, together with
      interfacial shear stress, affects the velocity distribution and flow pattern
      (e.g., reverse flow in the contact line region). We found that partial slip,
      rather than the commonly used stress-free condition, provided a more accurate
      description of the boundary condition at the confined air-water interface,
      reflecting the key role that surface/interface effects play in controlling flow
      behavior on the nanoscale and microscale.

PMID- 22867424
TI  - Differences between hospitals in attainment of parathyroid hormone treatment
      targets in chronic kidney disease do not reflect differences in quality of care.
AB  - BACKGROUND: Transparency in quality of care (QoC) is stimulated and hospitals are
      compared and judged on the basis of indicators of performance on specific
      treatment targets. In patients with chronic kidney disease, QoC differed
      significantly between hospitals. In this analysis we explored additional
      parameters to explain differences between centers in attainment of parathyroid
      hormone (PTH) treatment targets. METHODS: Using MASTERPLAN baseline data, we
      selected one of the worst (center A) and one of the best (center B) performing
      hospitals. Differences between the two centers were analyzed from the year prior
      to start of the MASTERPLAN study until the baseline evaluation. Determinants of
      PTH were assessed. RESULTS: 101 patients from center A (median PTH 9.9 pmol/l, in
      67 patients exceeding recommended levels) and 100 patients from center B (median
      PTH 6.5 pmol/l, in 34 patients exceeding recommended levels), were included.
      Analysis of clinical practice did not reveal differences in PTH management
      between the centers. Notably, hyperparathyroidism resulted in a change in therapy
      in less than 25% of patients. In multivariate analysis kidney transplant status,
      MDRD-4, and treatment center were independent predictors of PTH. However, when
      MDRD-6 (which accounts for serum urea and albumin) was used instead of MDRD-4,
      the center effect was reduced. Moreover, after calibration of the serum
      creatinine assays treatment center no longer influenced PTH. CONCLUSIONS: We show
      that differences in PTH control between centers are not explained by differences
      in treatment, but depend on incomparable patient populations and laboratory
      techniques. Therefore, results of hospital performance comparisons should be
      interpreted with great caution.

PMID- 22867426
TI  - Sport selection in under-17 male roller hockey.
AB  - Characteristics of 32 international and 41 local under-17 (U-17) (14.5-16.5
      years) roller hockey players were considered in the context of discrimination by
      competitive level using training history, anthropometry, skeletal maturation, and
      several laboratory and field performance tests. More international (42%) than
      local (22%) players were advanced in maturity status. International players had
      slightly less hockey experience (years), but had more practice sessions and match
      time (minutes) during the season. Local players were shorter and attained better
      performance in the 25-m dash, while international players performed better in sit
      ups, ball throw and 20-m shuttle run. The fatigue index derived from the Wingate
      anaerobic test was higher among local players, while peak torques of knee
      extension and flexion were greater in international players. Stepwise
      discriminant function correctly classified 85% of players by competitive level
      based on grip strength, ratio of eccentric and concentric knee extension, number
      of training sessions, playing time and fatigue index. The results suggested an
      interaction among strength, anaerobic fitness and training plus game time as
      factors in discriminating international from local level players and by inference
      in the selection and development of youth roller hockey players.

PMID- 22867427
TI  - Reducing harm from HIV/AIDS misconceptions among female sex workers in Tijuana
      and Ciudad Juarez, Mexico: A cross sectional analysis.
AB  - BACKGROUND: HIV prevalence is increasing among female sex workers (FSWs) in
      Mexico's Northern border region, who experience multiple occupational risks.
      Improving vulnerable populations' education, empowerment, and access to
      preventive services are important components of harm reduction strategies. Given
      the increasing interest in adapting harm reduction principles from drug use to
      sex work and other public health responses to the HIV epidemic, we used a sex
      work harm reduction framework to guide our investigation of FSWs' HIV knowledge.
      METHODS: From 2004-2006, FSWs aged >=18 years in Tijuana and Ciudad Juarez
      participated in a behavioral intervention study and completed structured
      interviews. Measures included HIV knowledge assessment and factors within each
      domain of our theoretical framework for sex work harms: (1) socio-demographic
      factors that may lead to sex work, (2) sex work characteristics and behaviors
      that may lead to harm, and (3) mutually reinforcing harms that lead to sex work
      and result from it (e.g., drug abuse). Negative binomial regression identified
      factors independently associated with suboptimal HIV knowledge (i.e., incorrect
      responses during the HIV knowledge assessment). RESULTS: Among 924 FSWs, the
      median proportion of incorrect responses was nearly one third (28% incorrect).
      Examination of item responses revealed misconceptions regarding specific
      transmission and prevention mechanisms, including prevention of mother to child
      transmission. Suboptimal HIV knowledge was independently associated with older
      age, lower education, living in Tijuana (vs. Ciudad Juarez), inconsistent condom
      use for vaginal sex with male clients, and lacking prior HIV testing.
      CONCLUSIONS: Our application of a sex work harm reduction framework to the study
      of FSWs' HIV knowledge is an important first step in enhancing HIV prevention
      efforts in Northern Mexican border cities. Our findings imply that interventions
      should identify and discredit local HIV misconceptions to improve knowledge of
      specific HIV transmission routes and self-protective strategies (e.g., condom
      negotiation). Interventions will require materials appropriate for women from
      diverse socio-economic backgrounds and may benefit from innovative harm reduction
      approaches such as peer education and outreach.

PMID- 22867429
TI  - Invasive lobular carcinoma with extracellular mucin as a distinct variant of
      lobular carcinoma: a case report.
AB  - The differences between invasive lobular and ductal carcinomas affect the
      diagnostic and therapeutic management for patients with breast cancer. In most
      cases, this can be accomplished because of distinct histomorphologic features.
      However, occasionally, this task may become quite difficult, in particular when
      dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma
      has been considered a variant of mucin-secreting carcinoma with only
      intracytoplasmic mucin. The presence of extracellular mucin is a feature of
      ductal carcinoma. Herein is presented a case of lobular carcinoma with
      extracellular and intracellular mucin in a 43-year-old female patient, and
      confirmed by immunohistochemistry. Up to the present, infiltrating lobular
      carcinoma displaying extracellular mucin has not been described in the literature
      except two case. Virtual slides: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744.

PMID- 22867428
TI  - Mice lacking the beta2 adrenergic receptor have a unique genetic profile before
      and after focal brain ischaemia.
AB  - The role of the beta2AR (beta2 adrenergic receptor) after stroke is unclear as
      pharmacological manipulations of the beta2AR have produced contradictory results.
      We previously showed that mice deficient in the beta2AR (beta2KO) had smaller
      infarcts compared with WT (wild-type) mice (FVB) after MCAO (middle cerebral
      artery occlusion), a model of stroke. To elucidate mechanisms of this
      neuroprotection, we evaluated changes in gene expression using microarrays
      comparing differences before and after MCAO, and differences between genotypes.
      Genes associated with inflammation and cell deaths were enriched after MCAO in
      both genotypes, and we identified several genes not previously shown to increase
      following ischaemia (Ccl9, Gem and Prg4). In addition to networks that were
      similar between genotypes, one network with a central core of GPCR (G-protein
      coupled receptor) and including biological functions such as carbohydrate
      metabolism, small molecule biochemistry and inflammation was identified in FVB
      mice but not in beta2KO mice. Analysis of differences between genotypes revealed
      11 genes differentially expressed by genotype both before and after ischaemia. We
      demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in
      beta2KO mice in both sham and MCAO conditions. As both genes are implicated in NF
      kappaB (nuclear factor kappaB) signalling, we measured p65 activity and TNFalpha
      (tumour necrosis factor alpha) levels 24 h after MCAO. MCAO-induced p65
      activation and post-ischaemic TNFalpha production were both greater in FVB
      compared with beta2KO mice. These results suggest that loss of beta2AR signalling
      results in a neuroprotective phenotype in part due to decreased NF-kappaB
      signalling, decreased inflammation and decreased apoptotic signalling in the
      brain.

PMID- 22867431
TI  - Limitations of an ocular surface inflammatory biomarker in impression cytology
      specimens.
AB  - CONTEXT: A number of ocular conditions, such as dry eye, are associated with
      inflammation on the surface of the eye leading to irritation and ocular pain.
      Many drugs such as chemotherapeutics, beta blockers, angiotensin-converting
      enzymes and so forth also cause dry eye but currently there are no validated
      ocular surface biomarkers available. OBJECTIVE: We evaluated sample stability,
      assay sensitivity, reproducibility and overall performance of impression cytology
      (IC) utilizing the cellular surface biomarker human leukocyte antigen DR-1 (HLA
      DR) as an ocular surface inflammatory biomarker by flow cytometry in a fit-for
      purpose validation study. Additionally, subjects classified as normal or having
      various degrees of dry eye were evaluated to determine if HLA-DR could
      demonstrate a clear separation between normal and dry eye samples. RESULTS: The
      assay demonstrated high dynamic range detecting a broad range of fluorescent
      intensities in healthy donors. Additionally, inter, intra and stability assay
      results demonstrated strong concordance and low variability. Overall CV% for both
      assays were less than 25% for all measured parameters. However, high variability
      was observed for donor samples assayed beyond day 10 post IC sample collection
      (4.2-110.8 CV%). DISCUSSION: HLA-DR expression demonstrated a progressive
      increase in patients with mild to severe levels of dry eye disease providing
      sufficient evidence it is sensitive enough to monitor inflammatory effects of dry
      eye when coupled with additional biomarkers and/or methodologies such as cytokine
      analysis or ICAM-1. This biomarker can be used to monitor ocular surface
      disorders in patients and to evaluate potential treatment options during drug
      development. Although our results demonstrate this methodology is reproducible
      for routine evaluation, limitations around sample integrity exist. CONCLUSION:
      The ocular cell surface inflammatory biomarker, HLA-DR coupled with impression
      cytology is a simple non-invasive robust, specific and reproducible assay that
      can be utilized to measure inflammatory infiltrates on the surface of the eye in
      IC samples less than 10-days old.

PMID- 22867432
TI  - Unconventional titania photocatalysis: direct deployment of carboxylic acids in
      alkylations and annulations.
AB  - Under dry, anaerobic conditions, TiO(2) photocatalysis of carboxylic acid
      precursors resulted in carbon-carbon bond-forming processes. High yields of
      dimers were obtained from TiO(2) treatment of carboxylic acids alone. On
      inclusion of electron-deficient alkenes, efficient alkylations were achieved with
      methoxymethyl and phenoxymethyl radicals. In reactions with maleic anhydride or
      maleimides, phenoxyacetic acid produced chromenedione derivatives in addition to
      adducts. These photocatalytic reactions are simple and cheap to perform, and the
      TiO(2) is easily removed by filtration. The anaerobic photocatalysis strategy
      offers a range of synthetic possibilities.

PMID- 22867430
TI  - Interacting with thioredoxin-1--disease or no disease?
AB  - SIGNIFICANCE: Many cardiovascular disorders are accompanied by a deregulated
      cellular redox balance resulting in elevated levels of intracellular reactive
      oxygen species (ROS). One major antioxidative cellular molecule is thioredoxin-1
      (Trx-1). Its indispensability is demonstrated by the embryonic lethality of Trx-1
      deficient mice. Trx-1 is ubiquitously expressed in cells and has numerous,
      diverse functions. It not only reduces oxidized proteins or, together with
      peroxiredoxins, detoxifies H(2)O(2), but also binds to several proteins and
      thereby regulates their functions. The interaction partners of Trx-1 differ
      depending on its localization in the cytosol or in the nucleus. RECENT
      ADVANCES/CRITICAL ISSUES: Over the past decade it has become clear that Trx-1 is
      not only critical for tumor functions, which has resulted in therapeutic
      approaches targeting this protein, but also essential for proper functions of the
      vasculature and the heart. Changes in post-translational modifications of Trx-1
      or in its interactions with other proteins can lead to a switch from a
      physiologic state of cells and organs to diverse pathologies. This review
      provides insights into the role of Trx-1 in different physiological situations
      and cardiac hypertrophy, ischemia reperfusion injury, heart failure,
      atherosclerosis, and diabetes mellitus type 2, underscoring the central role of
      Trx-1 in cardiovascular health and disease. FUTURE DIRECTIONS: Thus, the
      manipulation of Trx-1 activity in the heart and/or vasculature, for example, by
      small molecules, seems to be a promising therapeutic option in cardiovascular
      diseases, as general anti-oxidant treatments would not take into account
      interactions of Trx-1 with other proteins and also eliminate vital ROS.

PMID- 22867434
TI  - Radical pathway in catecholase activity with zinc-based model complexes of
      compartmental ligands.
AB  - Four dinuclear and three mononuclear Zn(II) complexes of phenol-based
      compartmental ligands (HL(1)-HL(7)) have been synthesized with the aim to
      investigate the viability of a radical pathway in catecholase activity. The
      complexes have been characterized by routine physicochemical studies as well as 
      X-ray single-crystal structure analysis:
      [Zn(2)(H(2)L(1))(OH)(H(2)O)(NO(3))](NO(3))(3) (1), [Zn(2)L(2)Cl(3)] (2),
      [Zn(2)L(3)Cl(3)] (3), [Zn(2)(L(4))(2)(CH(3)COO)(2)] (4), [Zn(HL(5))Cl(2)] (5),
      [Zn(HL(6))Cl(2)] (6), and [Zn(HL(7))Cl(2)] (7) [L(1)-L(3) and L(5)-L(7) = 2,6
      bis(R-iminomethyl)-4-methylphenolato, where R= N-ethylpiperazine for L(1), R = 2
      (N-ethyl)pyridine for L(2), R = N-ethylpyrrolidine for L(3), R = N-methylbenzene
      for L(5), R = 2-(N-methyl)thiophene for L(6), R = 2-(N-ethyl)thiophene for L(7),
      and L(4) = 2-formyl-4-methyl-6-N-methylbenzene-iminomethyl-phenolato].
      Catecholase-like activity of the complexes has been investigated in methanol
      medium by UV-vis spectrophotometric study using 3,5-di-tert-butylcatechol as
      model substrate. All  complexes are highly active in catalyzing the aerobic
      oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert
      butylbenzoquinone (3,5-DTBQ). Conversion of 3,5-DTBC to 3,5-DTBQ catalyzed by
      mononuclear complexes (5-7) is observed to proceed via  formation of two enzyme
      substrate adducts, ES1 and ES2, detected spectroscopically, a finding reported
      for the first time in any Zn(II) complex catalyzed oxidation of catechol. On the
      other hand, no such enzyme-substrate adduct has been identified, and  3,5-DTBC to
      3,5-DTBQ conversion is observed to be catalyzed by the dinuclear complexes (1-4)
      very smoothly. EPR experiment suggests  generation of radicals in the presence of
      3,5-DTBC, and that finding has been strengthened by cyclic voltammetric study.
      Thus, it may be proposed that the radical pathway is probably responsible for
      conversion of 3,5-DTBC to 3,5-DTBQ promoted by  complexes of redox-innocent
      Zn(II) ion. The ligand-centered radical generation has further been verified by
      density functional theory calculation.

PMID- 22867433
TI  - Roles of CREB in the regulation of FMRP by group I metabotropic glutamate
      receptors in cingulate cortex.
AB  - BACKGROUND: Fragile X syndrome is caused by lack of fragile X mental retardation
      protein (FMRP) due to silencing of the FMR1 gene. The metabotropic glutamate
      receptors (mGluRs) in the central nervous system contribute to higher brain
      functions including learning/memory, mental disorders and persistent pain. The
      transcription factor cyclic AMP-responsive element binding protein (CREB) is
      involved in important neuronal functions, such as synaptic plasticity and
      neuronal survival. Our recent study has shown that stimulation of Group I mGluRs
      upregulated FMRP and activated CREB in anterior cingulate cortex (ACC), a key
      region for brain cognitive and executive functions, suggesting that activation of
      Group I mGluRs may upregulate FMRP through CREB signaling pathway. RESULTS: In
      this study, we demonstrate that CREB contributes to the regulation of FMRP by
      Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB
      mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced
      compared to wild-type mice. However, the regulation of FMRP by Group I mGluRs is
      not altered by overexpression of Ca2+-insensitive mutant form of downstream
      regulatory element antagonist modulator (DREAM), a transcriptional repressor
      involved in synaptic transmission and plasticity. CONCLUSION: Our study has
      provided further evidence for CREB involvement in regulation of FMRP by Group I
      mGluRs in ACC neurons, and may help to elucidate the pathogenesis of fragile X
      syndrome.

PMID- 22867435
TI  - Alcohol consumption in relation to maternal deaths from induced-abortions in
      Ghana.
AB  - INTRODUCTION: The fight against maternal deaths has gained attention as the
      target date for Millennium Development Goal 5 approaches. Induced-abortion is one
      of the leading causes of maternal deaths in developing countries which hamper
      this effort. In Ghana, alcohol consumption and unwanted pregnancies are on the
      ascendancy. We examined the association between alcohol consumption and maternal
      mortality from induced-abortion. We further analyzed the factors that lie behind
      the alcohol consumption patterns in the study population. METHOD: The data we
      used was extracted from the Ghana Maternal Health Survey 2007. This was a
      national survey conducted across the 10 administrative regions of Ghana. The
      survey identified 4203 female deaths through verbal autopsy, among which 605 were
      maternal deaths in the 12 to 49 year-old age group. Analysis was done using
      Statistical software IBM SPSS Statistics 20. A case control study design was
      used. Cross-tabulations and logistic regression models were used to investigate
      associations between the different variables. RESULTS: Alcohol consumption was
      significantly associated with abortion-related maternal deaths. Women who had
      ever consumed alcohol (OR (adjusted) 2.6, 95% CI 1.38-4.87), frequent consumers
      (OR (adjusted) 2.6, 95% CI 0.89-7.40) and occasional consumers (OR (adjusted)
      2.7, 95% CI 1.29-5.46) were about three times as likely to die from abortion
      related causes compared to those who abstained from alcohol. Maternal age,
      marital status and educational level were found to have a confounding effect on
      the observed association. CONCLUSION: Policy actions directed toward reducing
      abortion-related deaths should consider alcohol consumption, especially among
      younger women. Policy makers in Ghana should consider increasing the legal age
      for alcohol consumption. We suggest that information on the health risks posed by
      alcohol and abortion be disseminated to communities in the informal sector where
      vulnerable groups can best be reached.

PMID- 22867436
TI  - Impact of physical and relational peer victimization on depressive cognitions in
      children and adolescents.
AB  - The purpose of this study is to find longitudinal evidence of the effect of
      targeted peer victimization (TPV) on depressive cognitions as a function of
      victimization type and gender. Prospective relations of physical and relational
      peer victimization to positive and negative self-cognitions were examined in a 1
      year, 2-wave longitudinal study. Self-reports of cognitions and both peer
      nomination and self-report measures of peer victimization experiences were
      obtained from 478 predominantly Caucasian children and young adolescents (Grades
      3-6 at the beginning of the study) evenly split between genders. As a result, (a)
      peer victimization predicted increases in negative cognitions and decreases in
      positive cognitions over time; (b) relational victimization was more consistently
      related to changes in depressive cognitions than was physical victimization; (c)
      the prospective relation between victimization and depressive cognitions was
      stronger for boys than for girls; and (d) when the overlap between relational and
      physical TPV was statistically controlled, girls experienced more relational TPV
      than did boys, and boys experienced more physical TPV than did girls. Peer
      victimization, particularly relational TPV, has a significant impact on
      children's depressive cognitions. This relation seems particularly true for boys.
      Implications for future research, clinical work with victimized youth at risk for
      depression, and school policy to help both victims and bullies are discussed.

PMID- 22867437
TI  - UHPLC-(ESI)QTOF MS/MS profiling of quercetin metabolites in human plasma
      postconsumption of applesauce enriched with apple peel and onion.
AB  - An ultrahigh pressure liquid chromatography accurate mass quadrupole time-of
      flight mass spectrometry with electrospray ionization (UHPLC-(ESI)QTOF MS/MS)
      method was developed for measuring individual quercetin metabolites in human
      plasma with high sensitivity and high selectivity. Quercetin (3,3',4',5,7
      pentahydroxyflavone) occurs as glycosides in foods. The composition of glycosides
      is species and cultivar specific. In humans, quercetin undergoes extensive
      biotransformation, resulting in a range of metabolites. The bioactivity of
      quercetin metabolites will depend on the type and position of the conjugates.
      Herein, individual quercetin metabolites (i.e., sulfate, glucuronide or methyl
      conjugates) were identified by accurate mass MS in human plasma (females = 8 and
      males = 8) over 24 h after consumption of applesauce enriched with either
      micronized apple peel (AP) or onion powder (OP). The AP and OP contained ~180
      MUmol of quercetin glycosides. The relative amounts of quercetin metabolites were
      quantified in plasma. The complement of identified quercetin metabolites was
      similar after consumption of AP and OP. Primary metabolites included the
      following: quercetin sulfate, quercetin glucuronide, and quercetin diglucuronide.
      A quercetin glutathione adduct was identified in negative ion mode but not
      apparent in positive ion mode. The pharmacokinetic parameters for AUC0-24 h and
      Cmax were significantly different for AP and OP. For example, consumption of the
      AP resulted in Cmax of quercetin sulfate, 4.6 ng/mL; quercetin glucuronide, 15.5
      ng/mL; quercetin diglucuronide, 9.3 ng/mL; quercetin glucuronide sulfate, 1.3
      ng/mL; methyl quercetin glucuronide, 7.5 ng/mL; and methyl quercetin
      diglucuronide, 3.6 ng/mL, whereas the OP resulted in Cmax of quercetin sulfate,
      37.3 ng/mL; quercetin glucuronide, 212.8 ng/mL; quercetin diglucuronide, 168.8
      ng/mL; quercetin glucuronide sulfate, 43.0 ng/mL; methyl quercetin glucuronide,
      90.1 ng/mL; methyl quercetin diglucuronide, 65.4 ng/mL. Gender-related
      differences in the AUC0-24 h for quercetin sulfate and quercetin sulfate
      glucuronide metabolites were also observed.

PMID- 22867438
TI  - Catalases and hydrogen peroxide metabolism.

PMID- 22867439
TI  - What inference for two-stage phase II trials?
AB  - BACKGROUND: Simon's two-stage designs are widely used for cancer phase II trials.
      These methods rely on statistical testing and thus allow controlling the type I
      and II error rates, while accounting for the interim analysis. Estimation after
      such trials is however not straightforward, and several different approaches have
      been proposed. METHODS: Different approaches for point and confidence intervals
      estimation, as well as computation of p-values are reviewed and compared for a
      range of plausible trials. Cases where the actual number of patients recruited in
      the trial differs from the preplanned sample size are also considered. RESULTS:
      For point estimation, the uniformly minimum variance unbiased estimator (UMVUE)
      and the bias corrected estimator had better performance than the others when the
      actual sample size was as planned. For confidence intervals, using a mid-p
      approach yielded coverage probabilities closer to the nominal level as compared
      to so-called 'exact' confidence intervals. When the actual sample size differed
      from the preplanned sample size the UMVUE did not perform worse than an estimator
      specifically developed for such a situation. Analysis conditional on having
      proceeded to the second stage required adapted analysis methods, and a uniformly
      minimum variance conditional estimator (UMVCUE) can be used, which also performs
      well when the second stage sample size is slightly different from planned.
      CONCLUSIONS: The use of the UMVUE may be recommended as it exhibited good
      properties both when the actual number of patients recruited was equal to or
      differed from the preplanned value. Restricting the analysis in cases where the
      trial did not stop early for futility may be valuable, and the UMVCUE may be
      recommended in that case.

PMID- 22867440
TI  - Light-triggered disassembly of amyloid fibrils.
AB  - There is growing demand for novel methods that could render the controlled
      disassembly of higher-order structures formed, for example, by peptides. Herein,
      we demonstrate such a method based on the application of a photocaged variant of
      the amino acid lysine, namely, lys(Nvoc). Specifically, we introduce lys(Nvoc)
      into the primary sequence of the amyloidogenic peptide, Abeta(16-22), at a
      position where the native side chain is known to play a key role in fibril
      formation via hydrophobic interactions. Both AFM and infrared spectroscopic
      measurements indicate that the resultant Abeta(16-22) mutant is able to form
      fibrils whereas, more importantly, the fibrils thus formed can be completely
      disassembled upon irradiation with near-UV light, which cleaves the photolabile
      Nvoc moiety and triggers the restoration of the lysine side chain. These results
      suggest that the generation of a single charge in a highly hydrophobic region of
      the fibrils is sufficient to promote their dissociation. Thus, we envisage that
      the current approach will find useful applications wherein controlled structural
      disassembly or content release is required.

PMID- 22867441
TI  - Patient access to complex chronic disease records on the Internet.
AB  - BACKGROUND: Access to medical records on the Internet has been reported to be
      acceptable and popular with patients, although most published evaluations have
      been of primary care or office-based practice. We tested the feasibility and
      acceptability of making unscreened results and data from a complex chronic
      disease pathway (renal medicine) available to patients over the Internet in a
      project involving more than half of renal units in the UK. METHODS: Content and
      presentation of the Renal PatientView (RPV) system was developed with patient
      groups. It was designed to receive information from multiple local information
      systems and to require minimal extra work in units. After piloting in 4 centres
      in 2005 it was made available more widely. Opinions were sought from both
      patients who enrolled and from those who did not in a paper survey, and from
      staff in an electronic survey. Anonymous data on enrollment and usage were
      extracted from the webserver. RESULTS: By mid 2011 over 17,000 patients from 47
      of the 75 renal units in the UK had registered. Users had a wide age range (<10
      to >90 yrs) but were younger and had more years of education than non-users. They
      were enthusiastic about the concept, found it easy to use, and 80% felt it gave
      them a better understanding of their disease. The most common reason for not
      enrolling was being unaware of the system. A minority of patients had security
      concerns, and these were reduced after enrolling. Staff responses were also
      strongly positive. They reported that it aided patient concordance and disease
      management, and increased the quality of consultations with a neutral effect on
      consultation length. Neither patient nor staff responses suggested that RPV led
      to an overall increase in patient anxiety or to an increased burden on renal
      units beyond the time required to enroll each patient. CONCLUSIONS: Patient
      Internet access to secondary care records concerning a complex chronic disease is
      feasible and popular, providing an increased sense of empowerment and
      understanding, with no serious identified negative consequences. Security
      concerns were present but rarely prevented participation. These are powerful
      reasons to make this type of access more widely available.

PMID- 22867442
TI  - Interventions to delay institutionalization of frail older persons: design of a
      longitudinal study in the home care setting.
AB  - BACKGROUND: Older people usually prefer staying at home rather than going into
      residential care. The Belgian National Institute for Health and Disability
      Insurance wishes to invest in home care by financing innovative projects that
      effectively help older people to stay at home longer. In this study protocol we
      describe the evaluation of 34 home care projects. These projects are clustered
      according to the type of their main intervention such as case management, night
      care, occupational therapy at home and psychological/psychosocial support. The
      main goal of this study is to identify which types of projects have the most
      effect in delaying institutionalization of frail older persons. METHODS/DESIGN:
      This is a longitudinal intervention study based on a quasi-experimental design.
      Researchers use three comparison strategies to evaluate intervention--comparison
      among different types of projects, comparisons between older persons in the
      projects and older persons not benefiting from a project but who are still at
      home and between older persons in the projects and older persons who are already
      institutionalized. Projects are asked to include clients who are frail and at
      risk of institutionalization. In the study we use internationally validated
      instruments such as the interRAI Home Care instrument, the WHO-QOL-8 and the
      Zarit Burden Interview-12. These instruments are filled out at baseline, at exit
      from the project and 6 months after baseline. Additionally, caregivers have to do
      a follow-up every 6 months until exit from the project. Criteria to exit the
      cohort will be institutionalization longer than 3 months and death. The main
      analysis in the study consists of the calculation of incidence rates, cumulative
      incidence rates and hazard rates of definitive institutionalization through
      survival analyses for each type of project. DISCUSSION: This research will
      provide knowledge on the functional status of frail older persons who are still
      living at home. This is important information to identify determinants of risk
      for institutionalization. The identification of effective home care projects in
      delaying institutionalization will be useful to inform and empower home care
      providers, policy and related decision makers to manage and improve home care
      services.

PMID- 22867443
TI  - Are we really measuring what we say we're measuring? Using video techniques to
      supplement traditional construct validation procedures.
AB  - Several researchers have persuasively argued that the most important evidence to
      consider when assessing construct validity is whether variations in the construct
      of interest cause corresponding variations in the measures of the focal
      construct. Unfortunately, the literature provides little practical guidance on
      how researchers can go about testing this. Therefore, the purpose of this article
      is to describe how researchers can use video techniques to test whether their
      scales measure what they purport to measure. First, we discuss how researchers
      can develop valid manipulations of the focal construct that they hope to measure.
      Next, we explain how to design a study to use this manipulation to test the
      validity of the scale. Finally, comparing and contrasting traditional and
      contemporary perspectives on validation, we discuss the advantages and
      limitations of video-based validation procedures.

PMID- 22867444
TI  - Implicit motives, explicit traits, and task and contextual performance at work.
AB  - Personality psychologists have long argued that explicit traits (as measured by
      questionnaires) channel the expression of implicit motives (as measured by coding
      imaginative verbal behavior) such that both interact in the prediction of
      relevant life outcome variables. In the present research, we apply these ideas in
      the context of industrial and organizational psychology and propose that 2
      explicit traits work as channels for the expression of 3 core implicit motives in
      task and contextual job performance (extraversion for implicit affiliation and
      implicit power; explicit achievement for implicit achievement). As a test of
      these theoretical ideas, we report a study in which employees (N = 241) filled
      out a questionnaire booklet and worked on an improved modern implicit motive
      measure, the operant motive test. Their supervisors rated their task and
      contextual performance. Results support 4 of the 6 theoretical predictions and
      show that interactions between implicit motives and explicit traits increase the
      explained criterion variance in both task and contextual performance.

PMID- 22867445
TI  - Jejunal lymphangioma: rare case of GI bleeding.

PMID- 22867446
TI  - Fabricated autologous epidermal cell sheets for the prevention of esophageal
      stricture after circumferential ESD in a porcine model.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is an accepted treatment for
      early esophageal carcinoma. However, resection of a large mucosal area, as with
      circumferential ESD, induces severe stricture formation. OBJECTIVE: To evaluate
      the efficacy of cultured autologous epidermal cell sheets to prevent severe
      esophageal constriction after circumferential ESD. DESIGN: Animal study. SETTING:
      University institute. INTERVENTION: Eight pigs underwent circumferential
      esophageal ESD while under general anesthesia. In 4 pigs, fabricated autologous
      epidermal cell sheets were endoscopically transplanted to the central ESD sites
      immediately after the ESD. The other 4 pigs underwent circumferential ESD only.
      Necropsy and histological assessment were performed at 1 and 2 weeks post-ESD.
      MAIN OUTCOME MEASUREMENTS: Weight gain, degree of mucosal constriction, and
      histological assessments. RESULTS: All pigs in the control group showed severe
      esophageal constriction after 2 weeks. The control and transplanted groups had
      weight gains of -10.3% and 0.3% (P = .03), respectively, and the mean degrees of
      constriction were 88% and 56% (P < .01), respectively. Early re-epithelialization
      and mild fibrosis in the muscularis were observed in the transplanted group.
      LIMITATIONS: Animal study, small sample size. CONCLUSIONS: Fabricated autologous
      skin epidermal cell sheets would be useful in preventing severe esophageal
      constriction after circumferential ESD.

PMID- 22867447
TI  - Clinical presentation, radiological features, and endoscopic management of
      mediastinal pseudocysts: experience of a decade.

PMID- 22867448
TI  - Carbon dioxide insufflation reduces number of postprocedure admissions after
      endoscopic resection of large colonic lesions: a prospective cohort study.
AB  - BACKGROUND: Endoscopic resection (ER) for large colonic lesions is a safe and
      effective outpatient treatment. Postprocedural pain creates concern for
      perforation and often results in postprocedure admission (PPA). Carbon dioxide
      (CO(2)) insufflation has been shown to reduce pain scores after routine
      colonoscopy, but an influence on more critical outcomes such as PPA has not been
      shown. OBJECTIVE: To assess the outcomes of patients undergoing ER for large
      colonic lesions, comparing those having air versus those having CO(2)
      insufflation. DESIGN: Prospective, observational, cohort study. SETTING:
      Academic, high-volume, tertiary-care referral center. PATIENTS: Consecutive
      patients referred for ER of sessile colorectal polyps >=20 mm. INTERVENTION: ER
      with air or CO(2). MAIN OUTCOME MEASUREMENTS: Rates of PPA, technical outcomes,
      complication rates. RESULTS: ER was performed on 575 lesions >=20 mm, 228 with
      CO(2) insufflation. Mean lesion size was 36.5 mm. Lesion and patient
      characteristics were similar in both groups. The use of CO(2) was associated with
      a 62% decrease in the PPA rate from 8.9% to 3.4% (P = .01). This was mainly
      because of an 82% decrease in PPA for pain from 5.7% to 1.0% (P = .006). There
      were no significant difference in the rates of complications. Multiple logistical
      regression was performed. The adjusted odds ratio (OR) of PPA (OR 0.39; 95%
      confidence interval [CI], 0.16-0.95; P = .04) and PPA for pain (OR 0.18; 95% CI,
      0.04-0.78; P = .02) in the CO(2) group remained significant. LIMITATIONS: Single
      center, nonrandomized study. CONCLUSION: CO(2) insufflation significantly reduces
      PPA after ER of large colonic lesions, primarily because of reduced PPA for pain.
      CO(2) insufflation should be routinely used during ER of large colonic lesions.

PMID- 22867449
TI  - Measurement procedures affect the interpretation of metatarsophalangeal joint
      function during accelerated sprinting.
AB  - The metatarsophalangeal joint (MPJ) is a significant absorber of energy in
      sprinting. This study examined the influence of MPJ axis choice and filter cut
      off frequency on kinetic variables describing MPJ function during accelerated
      sprinting. Eight trained sprinters performed maximal sprints along a runway.
      Three-dimensional high-speed (1000 Hz) kinematic and kinetic data were collected
      at the 20 m point. Three axis definitions for the five MPJs were compared. MPJ
      moments, powers and energies were calculated using different filter cut-off
      frequencies. The more anatomically appropriate dual axis resulted in less energy
      absorbed at the MPJ compared to the oblique axis which also absorbed less energy
      compared to the perpendicular axis. Furthermore, a low cut-off frequency (8 Hz)
      substantially underestimated MPJ kinematics, kinetics and the energy absorbed at
      the joint and lowered the estimate of energy production during push-off. It is
      concluded that a better understanding of MPJ function during sprinting would be
      obtained by using an oblique or anatomically appropriate representation of the
      joint together with appropriate kinematic data sampling and filtering so that
      high frequency movement characteristics are retained.

PMID- 22867501
TI  - In search of patient characteristics that may guide empirically based treatment
      selection for personality disorder patients-a concept map approach.
AB  - Using the concept map method, this study aimed to summarize and describe patient
      characteristics pertinent to treatment selection for patients with personality
      disorders (PDs). Initial patient characteristics were derived from the research
      literature and a survey among Dutch expert clinicians. Concept mapping is a
      formalized conceptualization procedure that describes the underlying cognitive
      structures people use in complex tasks, such as treatment allocation. Based on
      expert opinions of 29 Dutch clinicians, a concept map was generated that yielded
      eight domains of patient characteristics, i.e., Severity of symptoms, Severity of
      personality pathology, Ego-adaptive capacities, Motivation and working alliance,
      Social context, Social demographic characteristics, Trauma, and Treatment history
      and medical condition. These domains can be ordered along two bipolar axes,
      running from internal to external concepts and from vulnerability to strength
      concepts, respectively. Our findings may serve as input for the delineation of
      algorithms for patient-treatment matching research in PD.

PMID- 22867502
TI  - The distinguishing characteristics of narrative identity in adults with features
      of borderline personality disorder: an empirical investigation.
AB  - While identity disturbance has long been considered one of the defining features
      of Borderline Personality Disorder (BPD), the present study marks only the third
      empirical investigation to assess it and the first to do so from the perspective
      of research on narrative identity. Drawing on the rich tradition of studying
      narrative identity, the present study examined identity disturbance in a group of
      40 mid-life adults, 20 with features of BPD and a matched sample of 20 without
      BPD. Extensive life story interviews were analyzed for a variety of narrative
      elements and the themes of agency, communion fulfillment (but not communion), and
      narrative coherence significantly distinguished the stories of those people with
      features of BPD from those without the disorder. In addition, associations
      between the theme of agency and psychopathology were evident six and twelve
      months following the life story interview. This study seeks to bridge the
      mutually-informative fields of research on personality disorders and normal
      identity processes.

PMID- 22867503
TI  - Examining the utility of general models of personality in the study of
      psychopathy: a comparison of the HEXACO-PI-R and NEO PI-R.
AB  - The Five-Factor model is one of the most popular models of general personality
      but recently a competing model, the HEXACO, has been put forth as an alternative.
      In the current study, we compare the two models by examining the interrelations
      between their primary measures, the Revised NEO Personality Inventory (NEO PI-R)
      and the Revised HEXACO Personality Inventory (HEXACO-PI-R), and their relations
      with psychopathy in a sample of undergraduates (N = 290). Results revealed good
      convergence between conceptually related personality traits. Both inventories
      accounted for substantial proportions of variance in psychopathy scores although
      the HEXACO-PI-R accounted for a larger proportion. The findings are discussed in
      relation to the HEXACO domain of Emotionality, which functions differently than
      NEO PI-R Neuroticism. The results suggest that both measures assess psychopathy
      related traits, but the HEXACO-PI-R may offer a slight advantage.

PMID- 22867504
TI  - Personality disorders and physical health: a longitudinal examination of physical
      functioning, healthcare utilization, and health-related behaviors in middle-aged
      adults.
AB  - Personality disorders (PDs) have significant, long-term effects in many areas,
      including physical health outcomes such as increased risk for chronic disease and
      mortality. Although research has documented this detrimental impact in relation
      to long-term physical health, no one has explored the more immediate influence of
      disordered personality on aspects of physical functioning, such as pain level, or
      health-related behaviors, such as medication use. The present study examined the
      unique effects of PD features on physical functioning, medical resource
      utilization, and prescription medication use to determine potential risk
      associated with PDs. We studied an epidemiologically-based sample (N = 608) of
      Saint Louis residents (ages 55-64) over two time points (6 months apart). We
      found that disordered personality was significantly predictive of worse physical
      functioning, role limitations, fatigue, and pain at both time points, even when
      current health problems, the presence of depression, and health behaviors (i.e.,
      smoking, drinking, exercise) were controlled. PD features were also predictive of
      increased healthcare utilization and medication use at follow-up. These results
      suggest that the presence of disordered personality may be an important risk
      factor for worse functioning, regardless of actual health status.

PMID- 22867505
TI  - Phenotypic expression of schizotypal traits in an adolescent population.
AB  - The main goal of the present study was to examine the influence of gender and age
      in the phenotypic expression of schizotypal traits in a community sample of
      adolescents. The sample was composed of a total of 1,618 participants, 776 (48%)
      males, with a mean age of 15.9 years (SD = 1.2). The ESQUIZO-Q: Oviedo Schizotypy
      Assessment Questionnaire was used for the assessment of schizotypal traits, a
      measure specifically developed for its use in adolescents. The results showed
      that gender and age were two sociodemographical variables that influenced the
      expression of schizotypal features. The males in the study obtained higher mean
      scores than the females in the Negative dimension (Physical and Social
      Anhedonia); however, the females obtained higher mean scores in Magical Thinking,
      Lack of Close Friends, and Social Disorganization. With regard to age, the
      younger adolescents had lower scores in Odd Thinking and Language, Lack of Close
      Friends, Excessive Social Anxiety, and Social Disorganization compared to the
      older adolescents. This differential pattern is similar to the one found in
      patients with schizophrenia and in nonclinical young adults, and these findings
      improve our understanding about the phenotypic expression of schizotypy during
      adolescence.

PMID- 22867506
TI  - Are DSM-IV-TR borderline personality disorder, ICD-10 emotionally unstable
      personality disorder, and CCMD-III impulsive personality disorder analogous
      diagnostic categories across psychiatric nomenclatures?
AB  - This study examined the validity of the borderline construct which encompasses
      diagnostic criteria from the DSM-IV-TR Borderline Personality Disorder (BPD), ICD
      10 Emotionally Unstable Personality Disorder (EUPD), and CCMD-III Impulsive
      Personality Disorder (IPD) in a sample of 1,419 Chinese psychiatric patients.
      Participants completed the Chinese Personality Disorder Inventory and the Chinese
      Personality Assessment Inventory-2 assessing various disordered personality
      features. Adequate internal consistency was found for the borderline construct
      (alpha = .83). Exploratory factor analysis revealed two components: (1) affective
      and cognitive disturbances, and (2) impulse dysregulation, which were replicated
      by confirmatory factor analysis. Item analysis indicated that the various
      borderline criteria displayed similar levels of diagnostic efficiency, which does
      not support the elimination of fear of abandonment and transient psychotic
      features from the EUPD and IPD criteria set. Findings of this study suggest that
      BPD, EUPD, and IPD may represent analogous diagnostic categories across
      classification systems.

PMID- 22867507
TI  - Treatment outcome of 18-month, day hospital mentalization-based treatment (MBT)
      in patients with severe borderline personality disorder in the Netherlands.
AB  - Psychoanalytically oriented day hospital therapy, later manualized and named
      mentalization-based treatment (MBT), has proven to be a (cost-) effective
      treatment for patients with severe borderline personality disorder and a high
      degree of psychiatric comorbidity (BPD) in the United Kingdom (UK). As to yet it
      has not been shown whether manualized day hospital MBT would yield similar
      results when conducted by an independent institute outside the UK. We
      investigated the applicability and treatment outcome of 18-month, manualized day
      hospital MBT in the Netherlands by means of a prospective cohort study with 45
      Dutch patients with severe BPD and a high degree of comorbid Axis I and Axis II
      disorders. Outcomes were assessed each six months. Symptom distress, social and
      interpersonal functioning, and personality pathology and functioning all improved
      significantly, with effect sizes between 0.7 and 1.7. Suicide attempts, acts of
      self-harm, and care consumption were also significantly reduced. The results
      indicate that MBT can effectively be implemented in an independent treatment
      institute outside the UK. This study also supports the clinical effectiveness of
      manualized day hospital MBT in patients with severe BPD and a high degree of
      psychiatric comorbidity.

PMID- 22867508
TI  - Interpersonal patterns in borderline personality disorder.
AB  - Research has shown that a disturbed capacity to relate to others is a key feature
      of borderline personality disorder (BPD; e.g., Bender & Skodol, 2007; Gunderson,
      2007). However, few attempts have been made to determine if and how this
      disturbance translates into identifiable core interpersonal patterns. This study
      investigated the relationship patterns of 68 patients presenting with BPD.
      Vignettes of interpersonal interactions spontaneously reported by participants
      were rated using the Core Conflictual Relationship Theme (CCRT; Luborsky & Crits
      Christoph, 1990) method. Results of a factor analysis revealed six patterns of
      interactions: (1) interactions involving the ego ideal; (2) dependent-depressive
      interactions; (3) receptive interactions; (4) passive-submissive interactions;
      (5) successful interactions; and (6) sadomasochistic interactions. The clinical
      implications of these findings are discussed.

PMID- 22867509
TI  - The burden of disease among adolescents with personality pathology: quality of
      life and costs.
AB  - In adults, personality disorders are associated with a low quality of life and
      high societal costs. To explore whether these findings also apply to adolescents,
      131 adolescent patients were recruited from a mental health care institute in The
      Netherlands. Axis I and Axis II disorders were diagnosed using semi-structured
      interviews. The EuroQol EQ-5D was used to measure quality of life and costs were
      measured by the Trimbos and Institute for Medical Technology Assessment
      Questionnaire on Costs Associated with Psychiatric Illness. The mean EQ-5D index
      value was 0.55. The mean direct medical cost in the year prior to treatment was
      ?14,032 per patient. The co-occurrence of Axis I and Axis II disorders was a
      significant predictor of a low quality of life. Direct medical costs were higher
      for the depressive personality disorder. This study shows that the burden of
      disease among adolescents with personality pathology is high. This high burden
      provides evidence to suggest that further research and development of (cost
      )effective treatment strategies for this population may be worthwhile.

PMID- 22867510
TI  - Stress regulation and incision in borderline personality disorder--a pilot study
      modeling cutting behavior.
AB  - Emotion dysregulation in Borderline Personality Disorder (BPD) is characterized
      by high baseline negative intensity, high reactivity, and slow return to
      baseline. Patients with BPD often engage in self-injurious behavior because it
      leads to immediate relief of stress levels. We aimed to assess stress regulation
      as well as the influence of tissue damage on subjective (aversive tension) and
      objective (heart rate) stress correlates in BPD. In 14 unmedicated patients with
      BPD and 18 healthy controls, a stress induction was followed by an incision into
      the forearm conducted by an investigator. For aversive tension, we found elevated
      baseline levels as well as slower return to baseline in BPD. In controls,
      incision resulted in a short-term increase of aversive tension, whereas tension
      and heart rate decreased in the BPD group. Our preliminary results support the
      hypothesis that tissue damage may play a role in disturbed stress regulation in
      BPD.

PMID- 22867511
TI  - The relationship between agreeableness and the development of the working
      alliance in patients with borderline personality disorder.
AB  - The working alliance between therapist and patient is an important component of
      effective interventions for borderline personality disorder (BPD). The current
      study examines whether client personality affects the development of the working
      alliance during the treatment of BPD, and whether this influences treatment
      effectiveness. Data was based on 87 patients with BPD who were participants in a
      randomized controlled trial comparing Dialectical Behavior Therapy (DBT) and
      general psychiatric management. Higher levels of trait Agreeableness were
      associated with steeper increases in working alliance throughout treatment, but
      only in the DBT condition. Increases in working alliance were in turn associated
      with better clinical outcomes. Mediation models revealed a significant indirect
      path from Agreeableness to better clinical outcomes, mediated through larger
      improvements in working alliance over time. These results highlight the role that
      patient personality can play during the therapeutic process, with a specific
      focus on the importance of Agreeableness for alliance development.

PMID- 22867512
TI  - Psychometric evaluation of the Borderline Personality Disorder Severity Index-IV-
      adolescent version and parent version.
AB  - The Borderline Personality Disorder Severity Index-IV-adolescent and parent
      versions (BPDSI-IV-ado/p) are DSM-IV based semi-structured interviews for the
      assessment of the severity of symptoms of borderline personality disorder (BPD)
      in adolescents. The present study evaluates the psychometric properties of the
      BPDSI-IV-ado/p. The interviews were administered to 122 adolescents, aged 14-19
      years and their parents/caretakers who were referred to mental health centres for
      emotion regulation problems, and to 45 healthy controls. The interrater
      reliability and internal consistency of all nine subscales (following the nine
      BPD symptoms in DSM-IV) proved to be good to excellent. Discriminant, concurrent,
      and construct validity were satisfactory. Cut-off scores that optimize
      sensitivity and specificity were derived. Informant agreement between adolescents
      and parents/caretakers was modest. The results of this study suggest that the
      BPDSI-IV adolescent and parent versions are valid and reliable instruments for
      the assessment of BPD symptom severity in adolescents.

PMID- 22867514
TI  - Self-harm and psychosocial characteristics of looked after and looked after and
      accommodated young people.
AB  - Children and young people who are classed as "looked after" and "looked after and
      accommodated", have been identified as being especially at risk of self-harm,
      however there is little research that has assessed self-harm among these groups.
      This study investigates self-harm rates, distinguishing between cognitions and
      behaviours with non-suicidal and suicidal intent among the looked after and
      looked after and accommodated population of young people educated within
      mainstream institutions in West Central Scotland. Looked after young people who
      self-harmed were compared with looked after young people who had never self
      harmed on reasons for living, self-critical style, common life problems and
      academic self-esteem. An anonymous self-report questionnaire was used to survey
      102 looked after (LAC) and looked after and accommodated (LAAC) children and
      young people across 10 schools within 6 local authority regions in West Central
      Scotland that compared self-harmers (n = 32) with those who never self-harmed (n
      = 70). Thirty-two per cent of the looked after sample reported they had either
      thought about harming themselves or had actually engaged in self-harm behaviour.
      Self-harmers (including those who either thought about harming themselves and/or
      engaged in self-harm) differed from those who had never thought about harming
      themselves or engaged in self-harm behaviour, with significantly fewer reasons
      for living (RFL-A) and a more maladaptive self-critical style. The self-critical
      form of self-hate was found to be particularly important in predicting self-harm
      (thoughts and behaviours) among this sample of looked after and looked after and
      accommodated young people. Understanding the factors associated with self-harm
      and suicide risk is especially important given the already existing
      vulnerabilities to adverse outcomes associated with being looked after and looked
      after and accommodated. Strategies for the early identification of maladaptive
      behaviours among risk groups should take a wider approach beyond those already
      offered by health services. Utilising knowledge of behaviour and performance
      within additional key areas of young people's lives such as education could see a
      unique school-based intervention that can quickly and easily assess academic
      related factors linked with self-harm and offer a strategy for early
      identification of at risk children and young people.

PMID- 22867515
TI  - Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is
      essential for Ca2+ transfer from the sarcoplasmic reticulum to the mitochondria
      in the heart.
AB  - The structural proximity and functional coupling between the SR (sarcoplasmic
      reticulum) and mitochondria have been suggested to occur in the heart. However,
      the molecular architecture involved in the SR-mitochondrial coupling remains
      unclear. In the present study, we performed various genetic and Ca2+-probing
      studies to resolve the proteins involved in the coupling process. By using the
      bacterial 2-hybrid, glutathione transferase pull-down, co-immunoprecipitation and
      immunocytochemistry assays, we found that RyR2 (ryanodine receptor type 2), which
      is physically associated with VDAC2 (voltage-dependent anion channel 2), was co
      localized in SR-mitochondrial junctions. Furthermore, a fractionation study
      revealed that VDAC2 was co-localized with RyR2 only in the subsarcolemmal region.
      VDAC2 knockdown by targeted short hairpin RNA led to an increased diastolic
      [Ca2+] (calcium concentration) and abolishment of mitochondrial Ca2+ uptake.
      Collectively, the present study suggests that the coupling of VDAC2 with RyR2 is
      essential for Ca2+ transfer from the SR to mitochondria in the heart.

PMID- 22867516
TI  - A copper(II) thiolate from reductive cleavage of an S-nitrosothiol.
AB  - S-Nitrosothiols RSNO represent circulating reservoirs of nitric oxide activity in
      the plasma and play intricate roles in protein function control in health and
      disease. While nitric oxide has been shown to reductively nitrosylate copper(II)
      centers to form copper(I) complexes and ENO species (E = R(2)N, RO), well
      characterized examples of the reverse reaction are rare. Employing the copper(I)
      beta-diketiminate [Me(2)NN]Cu, we illustrate a clear example in which an RS-NO
      bond is cleaved to release NO(gas) with formation of a discrete copper(II)
      thiolate. The addition of Ph(3)CSNO to [Me(2)NN]Cu generates the three-coordinate
      copper(II) thiolate [Me(2)NN]CuSCPh(3), which is unstable toward free NO.

PMID- 22867517
TI  - Methods of staining and visualization of sphingolipid enriched and non-enriched
      plasma membrane regions of Arabidopsis thaliana with fluorescent dyes and lipid
      analogues.
AB  - BACKGROUND: Sterols and Sphingolipids form lipid clusters in the plasma
      membranes of cell types throughout the animal and plant kingdoms. These lipid
      domains provide a medium for protein signaling complexes at the plasma membrane
      and are also observed to be principal regions of membrane contact at the
      inception of infection. We visualized different specific fluorescent lipophilic
      stains of the both sphingolipid enriched and non-sphingolipid enriched regions in
      the plasma membranes of live protoplasts of Arabidopsis thaliana. RESULTS: Lipid
      staining protocols for several fluorescent lipid analogues in plants are
      presented. The most emphasis was placed on successful protocols for the single
      and dual staining of sphingolipid enriched regions and exclusion of sphingolipid
      enriched regions on the plasma membrane of Arabidopsis thaliana protoplasts. A
      secondary focus was placed to ensure that these staining protocols presented
      still maintain cell viability. Furthermore, the protocols were successfully
      tested with the spectrally sensitive dye Laurdan. CONCLUSION: Almost all existing
      staining procedures of the plasma membrane with fluorescent lipid analogues are
      specified for animal cells and tissues. In order to develop lipid staining
      protocols for plants, procedures were established with critical steps for the
      plasma membrane staining of Arabidopsis leaf tissue and protoplasts. The success
      of the plasma membrane staining protocols was additionally verified by
      measurements of lipid dynamics by the fluorescence recovery after photobleaching
      technique and by the observation of new phenomena such as time dependent lipid
      polarization events in living protoplasts, for which a putative physiological
      relevance is suggested.

PMID- 22867518
TI  - Respiratory distress of the newborn: congenital laryngeal atresia.
AB  - Congenital laryngeal atresia is a rare cause of respiratory distress of the
      newborn. The defect may be isolated or occur in association with other congenital
      abnormalities, notably the presence of a tracheoesophageal fistula, esophageal
      atresia, encephalocele, or Congenital High Airway Obstructive Syndrome (CHAOS).
      We present the case of a newborn with no identified intrapartum abnormalities
      with respiratory distress at birth secondary to near-complete laryngeal atresia.
      Management included tracheostomy, repeated endoscopic incisions, and serial
      balloon dilatations employing the topical use of Mitomycin C. Seven year follow
      up was significant for mobilization of the true vocal cords bilaterally, as well
      as successful decannulation.

PMID- 22867520
TI  - Clinically silent subdural hemorrhage causes bilateral vocal fold paralysis in
      newborn infant.
AB  - Bilateral congenital vocal fold paralysis (BVFP) may result from multiple
      etiologies or remain idiopathic when no real cause can be identified. If
      obstructive dyspnea is significant and requires urgent stabilization of the
      airway, then intubation is performed first and an MRI of the brain is conducted
      to rule out an Arnold-Chiari malformation that can benefit from a shunt procedure
      and thus alleviate the need for a tracheostomy. Clinically silent subdural
      hemorrhage without any birth trauma represents another cause of neonatal BVFP
      that resolves spontaneously within a month. It is of clinical relevance to
      recognize this potential cause of BVFP as its short duration may alleviate the
      need for a tracheostomy. In this article, we present such a case and review the
      literature to draw the otolaryngologist's attention to this possible etiology.

PMID- 22867519
TI  - Pie-slice tympanoplasty for transcanal removal of small congenital cholesteatoma.
AB  - OBJECTIVE: To describe a novel approach for removal of selected congenital
      cholesteatomas. METHODS: Description of technique and retrospective review of
      charts for patients undergoing procedure from January 1 to June 1, 2011. Two
      patients with congenital cholesteatomas localized to the middle ear necessitating
      transcanal surgical removal were identified. Using a transcanal approach, the
      "pie-slice" tympanic membrane flap was developed by incising the tympanic
      membrane anterior to the malleus, from the lateral process to the umbo. A second
      incision was then made anteriorly along an axis extending from the umbo to the 3
      o'clock position for the right ear (9-o'clock in the left ear). The flap was
      elevated allowing for visualization and access to the lesion anterior to the
      malleus. The cholesteatoma was removed. Otoendoscopes were used to visualize the
      middle ear and ensure complete removal. The tympanic membrane was repaired with a
      tragal perichondrium graft placed medial to the edges of the elevated pie-slice
      flap. The flap was then replaced laterally. RESULTS: Tympanic membranes are well
      healed in both patients after one year of follow-up with no evidence of disease
      and good hearing results. CONCLUSION: Pie-slice tympanoplasty is a simple and
      effective technique for removing selected localized congenital cholesteatomas and
      represents a novel approach to treating these entities that minimizes operative
      time and patient morbidity.

PMID- 22867521
TI  - Evaluation of antidiabetic potential of oyster mushroom (Pleurotus ostreatus) in
      alloxan-induced diabetic mice.
AB  - OBJECTIVES: To study the antidiabetic activity of Pleurotus ostreatus in normal
      and alloxan-induced diabetic mice. MATERIALS AND METHODS: Ethanolic extract of
      fruiting bodies of P. ostreatus was tested for their antidiabetic activity.
      BALB/C mice (25-30 g) were divided into four groups of six animals each normal
      control mice, diabetic control mice, diabetic mice posttreated with standard drug
      glibenclamide and diabetic mice treated with P. ostreatus ethanolic extract.
      Blood glucose level, biochemical parameters such as serum total cholesterol, LDL,
      HDL, VLDL, triglyceride creatinine, urea, and Serum glutamate oxaloacetate
      transaminase and Serum glutamate pyruvate transaminase were studied in alloxan
      induced diabetic mice after 15 days of treatment. RESULTS: Animals treated with
      the ethanolic extract of P. ostreatus showed a significant decrease in serum
      glucose level (p < 0.01). The posttreatment with P. ostreatus extract reduced
      serum cholesterol, triglyceride and LDL-cholesterol. The serum HDL cholesterol
      was significantly increased in posttreated groups. The serum creatinine, urea
      levels were significantly reduced in posttreated group, whereas the decrease in
      the body weight was arrested by administration of P. ostreatus extract to the
      animals. DISCUSSION AND CONCLUSION: The consumption of P. ostreatus produced a
      significant hypoglycemic effect in diabetic mice and it is capable of improving
      hyperlipidemia and the impaired kidney functions in alloxan-induced diabetic
      mice. Thus, indicating that the ethanolic extract of P. ostreatus could be added
      in the list of medicinal preparations beneficial in diabetes mellitus.

PMID- 22867522
TI  - Benign osteoblastoma of the ethmoid sinus.
AB  - Osteoblastoma is categorized as a benign bone-forming tumor, which occurs rarely
      in the craniofacial region. We report a case of osteoblastoma developed in the
      nasal cavity and ethmoid sinus in a 14-year-old girl whose chief symptom was
      nasal obstruction and exophthalmos on the right side. CT revealed the lesion
      having the same density as bone and a ground-glass border, expanding to the nasal
      and paranasal cavities. Complete removal was accomplished under endoscopic view,
      although the tumor was removed piece by piece. Histologic inspection showed
      exuberant osteoid trabeculae and immature bone formation by osteoblasts with
      vascularized connective tissue. We diagnosed the tumor as osteoblastoma based on
      the clinical presentation and the size of the tumor. No recurrence was evident at
      the 1-year follow-up visit.

PMID- 22867523
TI  - Monophasic synovial sarcoma of the nasopharynx.
AB  - Synovial sarcomas are rare, aggressive malignant neoplasms, and less than 10% of
      cases involve the head and neck. Cases that involve the nasopharynx are even more
      exceptional and little information is available concerning their diagnosis and
      management. We report the third case of synovial sarcoma of the nasopharynx,
      which was diagnosed as a monophasic type and was successfully treated with a
      complete surgical excision followed by irradiation. The present case indicates
      that appropriate immunohistochemical and cytogenetic analysis are essential for
      accurate diagnosis of monophasic synovial sarcoma in unusual locations. A review
      of the literature indicates that synovial sarcoma of the nasopharynx exhibits an
      improved prognosis following tumor resection and postoperative adjuvant radiation
      unless it invades adjacent bones, even though the tumor is larger than 4 cm.

PMID- 22867524
TI  - Regional control after concomitant chemoradiotherapy without planned neck
      dissection in node-positive head and neck squamous cell carcinomas.
AB  - OBJECTIVES: Although three-weekly high-dose (100mg/m(2)) cisplatin (three cycles)
      chemoradiotherapy has been considered a standard regimen for patients with
      advanced head and neck squamous cell carcinomas (HNSCC), this protocol is
      associated with significant acute and late toxicities. Therefore, weekly
      cisplatin at a dose of 40mg/m(2) has been used at our institution since 2006.
      This retrospective study was aimed at assessing the oncologic efficacy of weekly
      cisplatin chemoradiotherapy for the control of nodal metastasis. METHODS: We
      analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and
      concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the
      completion of chemoradiotherapy to evaluate nodal response. If residual neck
      disease was apparent or suspected, we performed early salvage neck dissection
      (ND). In cases with a complete response (CR), we took a "wait and see" approach.
      When no viable tumor cells were observed in the surgical specimens obtained by
      ND, nodal metastasis was defined as controlled by weekly cisplatin
      chemoradiotherapy alone. RESULTS: Nodal metastasis was evaluated as having a CR
      in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent
      primary tumors were observed in the other four patients (14%). Salvage primary
      resection and associated ND were performed for these four patients. In 7 of 12
      patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients,
      neck diseases were controlled by chemoradiotherapy alone (not including salvage
      by ND). In 27 of 28 patients, neck diseases were controlled by the overall
      treatment (including salvage by ND). The rate of nodal control by
      chemoradiotherapy alone and by the overall treatment was found to be 82.0% and
      96.3%, respectively, using the Kaplan-Meier method. The three-year overall and
      disease free survival rates were 86.8% and 80.8%, respectively. CONCLUSION:
      Concomitant weekly cisplatin at a dose of 40mg/m(2) chemoradiotherapy showed a
      good control rate of not only primary lesions but also neck diseases.

PMID- 22867525
TI  - Visualization of endolymphatic hydrops and correlation with audio-vestibular
      functional testing in patients with definite Meniere's disease.
AB  - OBJECTIVES: Visulization of endolymphatic hydrops has been reported using
      magnetic resonance imaging (MRI) in patients with Meniere's disease. However, the
      relationship between the endolymphatic hydrops visualized by MRI and audio
      vestibular functional tests have not been sufficiently investigated, such as pure
      tone audiometry (PTA), electrocochleography (EcoG), and vestibular evoked
      myogenic potential (VEMP). METHODS: Here we attempted to visualize endolymphatic
      hydrops in patients with Meniere's disease using 3Tesla (3T)-MRI following
      intratympanic gadolinium-diethylene-triamnie petaaetic acidbis (Gd-DTPA)
      injection and correlated the presence of hydrops with auditory testing. Following
      intratympanic Gd-DTPA contrast injections in 26 patients diagnosed as having
      definite Meniere's disease, 3D-fluid-attenuated inversion recovery (3D-FLAIR)
      sequence imagings were performed. The PTA, EcoG, and VEMP testing was done
      bilaterally. Patients had typical results of auditory testing for Meniere's
      disease. RESULTS: The 3D-FLAIR MRI clearly demonstrated endolymphatic hydrops
      with signal voids in the cochlea (81%) and saccule (69%) in the definite
      Meniere's disease group. Auditory tests verified that the visualized cochlear
      hydrops (basal turn) was correlated with a high tone hearing threshold in PTA and
      an abnormal EcoG. Though the absence of VEMP did not correlate with vestibular
      hydrops on MRI, large vestibular hydrops were detected by imaging. This study
      demonstrates that endolymphatic hydrops could be visualized by 3D-FLAIR MRI in
      Meniere's disease patients. CONCLUSION: Cochlea hydrops and vestibular (saccular)
      hydrops are readily visualized using these techniques. Hydrops, as visualized on
      MRI, may be a reliable means to diagnosis Meniere's disease; this is supported by
      appropriate correlations with auditory vestibular functional testing.

PMID- 22867526
TI  - Burden of leprosy in Malawi: community camp-based cross-sectional study.
AB  - BACKGROUND: Although leprosy was eliminated globally in 2000, the disease
      continues to be the significant cause of peripheral neuropathy, disability and
      disfigurement in some developing countries. However, recent  population-based
      prevalence data are lacking to inform evidence-based renewed commitment for the
      final push for leprosy elimination at national and sub-national levels. METHODS:
      Community camp-based cross-sectional descriptive study was conducted in four
      selected districts. World Health Organisation guidelines and tools for leprosy
      elimination monitoring were used to evaluate the Malawi National Leprosy
      Programme. RESULTS: A total of 6,338 people (60% females, 35% children aged less
      than 15 years) were examined for leprosy and other skin diseases. Prevalence of
      skin diseases was 18%, the commonest being fungal (9%), eczema/dermatitis (3%)
      and leprosy (1%). Of the fungal skin conditions, pityriasis versicolor and Tinea
      capatis were the commonest (22% and 21% respectively) then Tinea corporis (9%),
      Tinea cruris (6%) and Tinea pedis (2%). A total of 66 leprosy cases were detected
      out of 6,338 people screened giving a prevalence of 104.1 per 10,000 population
      (range by district 67.1 to 194.1). Of the leprosy cases, 37 were new, 6 were
      defaulters and 23 were on treatment, 30 were females and 9 were children aged
      less than 15 years old. Of the 37 new leprosy cases, 9 (24.3%) were children, 25
      (67.6%) had 1-5 leprosy lesions and 8 (21.6%) had grade 2 disability. The most
      frequent location of leprosy lesions was the head and neck (24.1%), arms (24.1%),
      chest (17.2%), legs (13.8%), back (13.8%) and abdomen (7.0%). Between 2006 and
      2011, trends of leprosy prevalence and detection increased, prevalence/detection
      ratios were over 1 and cure rates by cohort analysis of 2009 multibacillary and
      2010 paucibacillary cases were 33% and 63% respectively far below the expected
      80% although the national prevalence remained at less than 1 case per 10,000
      population. CONCLUSION: Leprosy was still an important public health problem in
      Malawi. Improving knowledge and skills of health workers, registration and
      recording of data, contact tracing, decentralisation and integration of treatment
      to health centres and introduction of leprosy awareness days and community-based
      surveillance could help to improve early detection, treatment, case holding and
      prevention of disabilities.

PMID- 22867527
TI  - Synthesis and in vitro antiproliferative activity of platinum(II) complexes with
      N-monoalkyl 1R,2R-diaminocyclohexane as ligands.
AB  - Nine dichloridoplatinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane
      as ligands were synthesized and spectrally characterized. Among them, the crystal
      structure of a typical complex has been determined by X-Ray diffraction. All
      compounds were evaluated for their in vitro antitumor activity against four human
      cancer cell lines, which showed selective cytotoxicity comparable to that of
      positive agents against A549 (human non-small cell lung cancer) cell line.
      Especially complex 3, cis-[(1R,2R)-N(1)-2-butyl-1,2-diaminocyclohexane-N,N']
      dichloroplatinum(II), was much more active in vitro (IC(50) = 1.82 MUM) than
      cisplatin against A549. The structure-activity relationship was summarized
      according to the cytotoxicity and QSAR properties. In addition, flow cytometry
      and agarose gel electrophoresis experiments were also applied to investigate the
      mode of action of the representative complexes.

PMID- 22867528
TI  - Synthesis, screening and computational investigation of pentacycloundecane
      peptoids as potent CSA-HIV PR inhibitors.
AB  - Herein, we present the first pentacycloundecane (PCU) diol peptoid derived HIV
      protease inhibitors with IC(50) values ranging from 6.5 to 0.075 MUM. Five
      derivatives were synthesized in an attempt to understand the structure activity
      relationship of this class of compounds for HIV protease inhibition. NMR
      spectroscopy (new Efficient Adiabatic Symmetrized Rotating Overhauser Effect
      Spectroscopy, EASY-ROESY) was employed to determine the predominant conformation
      of the active compound. In this study docking studies and MD simulations provided
      insight into the binding theme of this class of peptoid inhibitors to the CSA-HIV
      PR active site. Conserved and stable hydrogen bonding between the hydroxyl groups
      of the inhibitors and the active site Asp25/Asp25' residues were observed from
      the docking and along the MD trajectories.

PMID- 22867529
TI  - Synthesis, characterization, screening and docking analysis of 4
      anilinoquinazoline derivatives as tyrosine kinase inhibitors.
AB  - We report here the design and synthesis of a series of 4-anilinoquinazoline
      derivatives, of which 7 compounds were crystallographically characterized, as
      epidermal growth factor receptor (EGFR) inhibitors by modifications on the
      aniline ring or at the 6-alkoxy site of the 6,7-dimethoxy-4-anilinoquinazoline
      pharmacophore. The relative inhibition efficiency on EGFR of all as-prepared
      compounds were measured and ordered, and the IC50 values of nine highly active
      compounds were determined by ELISA. Docking studies indicated that all 4
      anilinoquinazoline derivatives could be inserted into the ATP-binding pocket of
      the EGFR via indirect docking, and that the modifications at the 3'-position of
      the anilino group and 6-alkoxy site of the quinazoline ring have little
      interference with the formation of the two essential H-bonds between the N3 of
      the quinazoline ring and Thr766 through a water molecule, and the N1 of the
      quinazoline ring and N-H of Met769. The displacing of the phenyl at 4-position
      with pyridinyl dramatically reduces the activity of the quinazoline
      pharmacophore, the resulting derivative (10) being the least active compound. The
      docking results also showed that the formation of new H-bonds between the N-H of
      the ethylenediamine group linked to the 6-alkoxy site and Asp776/Cys773 in the
      binding pocket of EGFR makes compounds 19 (IC50=12.1+/-1.6 nM) and 20
      (IC50=13.6+/-0.8 nM) the most potent EGFR inhibitors in this class and worthy of
      further modification to obtain more potent anticancer compounds.

PMID- 22867530
TI  - Cell death triggered by synthetic flavonoids in human leukemia cells is amplified
      by the inhibition of extracellular signal-regulated kinase signaling.
AB  - A new class of methyl esters of flavonoids, with different substituents on the B
      ring were synthesized and evaluated for their antiproliferative activity against
      the human leukemia cell line HL-60. The presence of either a methyl group (1f) or
      a chlorine atom (1o) at position 2' of the B ring played an important role in
      affecting antiproliferative activity. The cytotoxic effects of these compounds
      were accompanied by the concentration- and time-dependent appearance of DNA- and
      nuclear-fragmentation, increase in the percentage of sub-G(1) cells, and
      processing of multiple caspases and poly(ADP-ribose)polymerase cleavage.
      Pretreatment of cells with the specific mitogen-activated extracellular kinases
      (MEK) 1/2 inhibitor PD98059, together with 1f and 1o, resulted in an important
      enhancement of cell death, which might have clinical implications for the use of
      both compounds in combination with MEK 1/2 inhibitors as potential therapeutic
      agents.

PMID- 22867532
TI  - Solid-state phase transitions of DL-aminobutyric acid.
AB  - Four polymorphs are known for the amino acid racemate DL-aminobutyric acid: one
      tetragonal form B and three monoclinic forms A, C, and D for which two solid
      solid phase transitions take place between 209 and 337 K. The intermediate form
      A, in space group P2(1)/c, is known to display disorder in the crystalline state
      with the ethyl side chain occupying three different conformations. The high
      temperature form D and the low temperature form C have been assumed to display a
      similar type of disorder in the space group C2/c. The present investigation, on
      the basis of high quality crystal structures at 100 K (C form), 220 K (A form),
      295 K (A form), and 295 K (D form), provides updated results for all three forms
      and in particular demonstrates that the A -> C and A -> D transitions in fact
      involve only a partial space group conversion, so that two monoclinic phases are
      simultaneously present at high and low temperatures. To the best of our
      knowledge, such a phenomenon has not been observed previously for an organic
      molecule. The nonroutine refinement of the crystallographic data was performed
      with a specially adapted version of the program JANA2006. The observed polymorphs
      are compared with those found for DL-norvaline, DL-norleucine, and DL-methionine.

PMID- 22867531
TI  - Obesity and elevated blood pressure among adolescents in Lagos, Nigeria: a cross
      sectional study.
AB  - BACKGROUND: Childhood obesity and associated hypertension are major public health
      concerns globally. This study aimed to determine the prevalence of obesity and
      the associated risk of high blood pressure among Nigerian adolescents. METHODS: A
      cross-sectional school-based study of 885 apparently healthy adolescents was
      performed. Weight, height and blood pressure (BP) were measured using standard
      methods. Body mass index (BMI) was calculated and categorized by age, sex and
      percentile. Obesity and overweight were defined as: >= 95th and 85th to < 95th
      percentiles, respectively, for age, sex and height. Subjects were sub-categorized
      into age 10-13 years (A) and 14-17 years (B). The odds ratio for pre-hypertensive
      and hypertensive range BP by age and BMI were generated. Significance was set at
      P < 0.05. RESULTS: The prevalence of overweight and obesity were 13.8% and 9.4%,
      respectively. The prevalence of hypertensive range systolic BP in obese versus
      normal BMI females was 16% versus 23% (p=0.00) and 12.1% versus 6.4% (p=0.27) in
      males. The prevalence of hypertensive range diastolic BP in obese versus normal
      BMI females was 12% versus 1.4% (p=0.00) and 15.2% versus 3.5% (p=0.01) in males.
      BMI in group B was significantly associated with pre-hypertensive and
      hypertensive range systolic BP in overweight (P = 0.01, P = 0.002) and obese
      subjects (P = 0.00, P = 0.00) and with hypertensive range diastolic BP (P = 0.00)
      only in obese subjects. The only significant association in group A was between
      obesity and pre-hypertensive range diastolic BP (P = 0.00). CONCLUSION: The
      prevalence of hypertensive range BP among obese Nigerian adolescents was high.
      Screening for childhood obesity and hypertension, and long-term follow-up of
      obese adolescents into adulthood are recommended.

PMID- 22867533
TI  - Automated TIMI frame counting using 3-d modeling.
AB  - Three dimensional coronary modeling and reconstruction can assist in the
      quantitative analysis of coronary flow velocity from 2-d coronary images. In this
      paper a novel method to assess coronary flow velocity is proposed. First, 3-d
      models of the coronary arteries are estimated from bi-plane X-ray images using
      epipolar constraint energy minimization for the selected fiducial points like
      bifurcations, and subsequently 3-d B-spline energy minimization for the arterial
      segments. A 4-d model is assembled from a set of 3-d models representing
      different phases of the cardiac cycle. The 4-d model is fitted to the 2-d image
      sequences containing basal or hyperemic blood flow information. Then, by counting
      the frames in analogy with TIMI frame counting, an index of the mean coronary
      flow velocity can be estimated. Our experimental results show that the algorithm
      correlates with r=0.98 (P<0.0001, 95% CI 0.92-0.99) to the clinical measurements
      of the TFC.

PMID- 22867534
TI  - In 2005, the School of Pharmaceutical Sciences of the University of Geneva and
      Lausanne was inaugurated. Introduction.

PMID- 22867535
TI  - The School of Pharmacy Geneva-Lausanne (EPGL) - the first ten years.
AB  - With the creation of the School of Pharmacy Geneva-Lausanne (EPGL) in 2003,
      cantons Geneva and Vaud pooled their resources with the objective of reinforcing
      the research and teaching in the pharmaceutical sciences. Its core research units
      cover all aspects of fundamental pharmaceutical  research and include
      collaborative research with the University Hospitals of Geneva and Lausanne.

PMID- 22867536
TI  - New expression method and characterization of recombinant human granulocyte
      colony stimulating factor in a stable protein formulation.
AB  - Human recombinant granulocyte colony stimulating factor (rhG-CSF) is widely used
      in hematology and oncology for the treatment of neutropenia, for the restoration
      of neutrophil production after bone marrow transplantation, for myelodysplastic
      syndromes, and aplastic anemia. The E. coli  expression system is commonly used
      for fast recombinant production of rhG-CSF at a large scale. We have applied a
      novel autoinduction method for the batch expression of rhG-CSF to study whether
      this new system would increase cell mass and target-protein yield compared to
      conventional E. coli  cell culture and induction with isopropyl beta-D
      thiogalactopyranoside (IPTG). We could demonstrate 3-fold higher culture
      densities and a 5-fold higher protein yield compared to IPTG induction without
      the need to monitor cell growth in a shortened 24 h expression procedure. rhG-CSF
      expressed  in autoinduction media was successfully extracted from E. coli
      inclusion bodies and refolded by dialysis. After size exclusion chromatography
      (SEC) purification, rhG-CSF showed similar conformation, biological activity and
      aggregation profile compared to the commercially available biosimilar 
      TEVAgrastim((r)) (TEVA Pharma AG). Expression by autoinduction is suggested as a
      cost- and time-effective method for rhG-CSF production.

PMID- 22867537
TI  - How to increase the safety and efficacy of compounds against neurodegeneration? A
      multifunctional approach.
AB  - Successful drug design requires not only the detailed knowledge of the
      pharmacokinetic and pharmacodynamic profiles of the drug candidate portfolio but
      also a thorough documentation of the possible toxic effects on humans and the
      environment. Thus, experimental and computational strategies  able to measure or
      predict specific profiles of designed compounds related to their potential
      toxicity are highly desired. Moreover, a strategy to avoid toxic effects thus
      enhancing the potential efficacy of drug candidates is of great interest. To
      fulfil this aim, the pharmacochemistry research  unit at the EPGL has recently
      developed and improved methodologies that detect the potential human health and
      environmental hazards of compounds active against neurodegeneration at an early
      stage. A three-step strategy is presented herein. In particular, i) an
      alternative index to model the  bioconcentration of chemicals in the environment
      was determined; ii) the antioxidant activity of chemical species against free
      radicals was evaluated. Moreover, since antioxidants play a key role in both
      toxicity prevention and neuroprotection, iii) the potential interaction of such
      compounds  with enzymatic targets involved in the neurodegenerative cascade was
      investigated in silico.

PMID- 22867538
TI  - Dosage optimization of treatments using population pharmacokinetic modeling and
      simulation.
AB  - Pharmacokinetic variability in drug levels represent for some drugs a major
      determinant of treatment success, since sub-therapeutic concentrations might lead
      to toxic reactions, treatment discontinuation or inefficacy. This is true for
      most antiretroviral drugs, which exhibit high inter-patient  variability in their
      pharmacokinetics that has been partially explained by some genetic and non
      genetic factors. The population pharmacokinetic approach represents a very useful
      tool for the description of the dose-concentration relationship, the
      quantification of variability in the target  population of patients and the
      identification of influencing factors. It can thus be used to make predictions
      and dosage adjustment optimization based on Bayesian therapeutic drug monitoring
      (TDM). This approach has been used to characterize the pharmacokinetics of
      nevirapine (NVP) in 137  HIV-positive patients followed within the frame of a TDM
      program. Among tested covariates, body weight, co-administration of a cytochrome
      (CYP) 3A4 inducer or boosted atazanavir as well as elevated aspartate
      transaminases showed an effect on NVP elimination. In addition, genetic
      polymorphism  in the CYP2B6 was associated with reduced NVP clearance.
      Altogether, these factors could explain 26% in NVP variability. Model-based
      simulations were used to compare the adequacy of different dosage regimens in
      relation to the therapeutic target associated with treatment efficacy. In
      conclusion,  the population approach is very useful to characterize the
      pharmacokinetic profile of drugs in a population of interest. The quantification
      and the identification of the sources of variability is a rational approach to
      making optimal dosage decision for certain drugs administered chronically.

PMID- 22867539
TI  - Validation of the simplified UVB model to assess the pharmacodynamics of
      analgesics in healthy human volunteers.
AB  - A pharmacokinetic/pharmacodynamic, randomized, crossover, placebo-controlled
      study was conducted in healthy human volunteers with the primary objective of
      exploring the existence of a positive interaction between paracetamol 1 g and
      ketorolac 20 mg intravenously on experimental pain  models. Further, the
      simplified UVB model was validated as a screening tool for analgesics or a
      combination of analgesics in clinical drug development. It was observed that the
      UVB irradiation induced primary hyperalgesia, evidenced by significant decreases
      of the heat pain threshold from  (mean +/- SD) 46.9 +/- 1.1  degrees C to 40.1 +/
      1.7  degrees C (p <0.001) and of the mechanical pain threshold (62% decrease). A
      small intra- and inter-individual variability was observed as well as consistent
      intra-day stability for the heat pain threshold. The UVB irradiation  also
      resulted in the development of an area of secondary hyperalgesia of 21.3 +/- 11.3
      cm(2). The mechanical pain threshold and area of secondary hyperalgesia showed
      small intra-individual variability and consistent intra-day stability. However, a
      greater variability was observed  between subjects, which suggests that a
      crossover design would allow limiting the number of subjects.

PMID- 22867540
TI  - The hospital pharmacist: an important contributor to improved patient safety in
      the hospital.
AB  - Injectable drugs are high-risk products and their reconstitution in hospital
      wards is a potential source of errors. Thus, in order to secure the
      reconstitution process and thereby improve safety, the pharmacy department of
      Lausanne University Hospital is focusing on developing ready-to-use  forms
      (CIVAS). These preparations are compounded in controlled clean rooms and are
      analyzed prior to release. In the intensive care unit, amiodarone 12.5 mg/mL in
      glucose 5% is one of the high-risk preparations, which has led the pharmacy to
      develop a ready-to-use solution. To this end, a  one-year stability study was
      initiated, and the preliminary results (after six months) are illustrated here. A
      stability-indicating HPLC method was developed and validated for monitoring the
      concentration of amiodarone. Batches were stored at 5  degrees C and 30  degrees
      C, which were analyzed immediately  after preparation, after one, two, four and
      six months of storage. The pH and osmolality values were monitored at the
      respective time intervals. It was observed that after six months, all the results
      were within specifications. However, the pH values started to decrease after two
      months when  amiodarone was stored at 30  degrees C. After six months, a
      degradation peak appeared on the chromatogram of these solutions, which suggested
      that amiodarone is more stable at 5  degrees C. The preliminary results obtained
      in this study indicated that injectable amiodarone solutions are stable for  six
      months under refrigerated storage conditions. The study is ongoing.

PMID- 22867541
TI  - New roles for community pharmacists in modern health care systems: a challenge
      for pharmacy education and research.
AB  - The academic activities led by the Unit of Community Pharmacy can be classified
      as translational. Our group is interested in person-centered pharmaceutical
      services aimed at a more responsible use of drugs (effectiveness, safety,
      efficiency) in collaboration with physicians and other  health care professionals
      in a primary care setting. The following domains of education and research are
      high priorities for our group: medication therapy management, medication
      adherence, integrated care, individualization of therapies, care management for
      the elderly and e-health.

PMID- 22867542
TI  - Pharmaceutical technology at the service of targeted drug delivery.
AB  - Research in pharmaceutical technology has drifted from formulation of systems
      with improved drug absorption and bioavailability to systems targeting molecular
      sites of diseases. The research unit of Pharmaceutical Technology from the
      University of Geneva focuses on the development of  systems for both diagnostic
      and therapeutic purposes. Three types of constructs for targeting are reviewed.
      With a fine-tuning of size and surface composition, polymeric nanoparticles are
      developed to improve detection of micrometastasis by fluorescence imaging.
      Furthermore, surface coating  with specific antibodies increase the therapeutic
      efficiency of the encapsulated chemotherapeutic agent for tumor treatment in
      animal models. Constructs that are activated by remote sources of energy are
      investigated in the unit. For instance, microbubbles bearing specific antibody
      fragments  at their surface are useful contrast agents for ultrasound molecular
      imaging. Microbubbles, if combined with a thrombolytic drug and ultrasound,
      improve clot lysis, which is promising for stroke treatments. Enzymatically
      activated prodrug scaffolds are also under development. With this approach, 
      intrinsic enzymatic activity of a diseased tissue activates the formulations.
      This concept led to the development of theranostic agents that can be used for
      both diagnostic and therapeutic purposes.

PMID- 22867543
TI  - The pharmaceutical biochemistry group: where pharmaceutical chemistry meets
      biology and drug delivery.
AB  - Successful drug discovery and development of new therapeutics is a long,
      expensive multidisciplinary process needing innovation and the integration of
      smart cutting edge science and technology to overcome the challenges in taking a
      drug from the bench to the bedside. The research activities  of the
      Pharmaceutical Biochemistry group span the drug discovery and development
      process, providing an interface that brings together pharmaceutical chemistry,
      biochemistry, structural biology, computational chemistry and biopharmaceutics.
      Formulation and drug delivery are brought into play  at an earlier stage when
      facing the perennial challenge of transforming a potent molecule in vitro into a
      therapeutic agent in vivo. Concomitantly, drug delivery results can be understood
      at a molecular level. This broad range of interdisciplinary research activities
      and competences  enables us to address key challenges in modern drug discovery
      and development, provides a powerful collaborative platform for other
      universities and the pharmaceutical industry and an excellent training platform
      for pharmacists and pharmaceutical scientists who will later be involved in drug 
      discovery and development.

PMID- 22867544
TI  - Plants as a source of therapeutic and health products.
AB  - The research unit of Pharmacognosy is mostly working on the biological activity
      and safety of natural products, as well as herbal dietary supplements. One of the
      focuses relies on finding new cancer chemopreventive compounds by means of a
      battery of short-term in vitro bioassays developed  to monitor inhibition of
      tumorigenesis at various stages. Neglected diseases are a major problem in
      developing countries. Therefore, the search for new or improved treatments is
      also needed and consists of another area of research of the unit. For both
      projects, in-depth mechanistic studies,  as well as in vitro and in vivo
      absorption and metabolization experiments are performed. Problems related to
      undeclared, unauthorized or toxic botanicals in herbal dietary supplements are of
      growing importance as they generally have not gone through a rigorous drug
      testing process as for therapeutic  phytochemicals. For this, a generic method
      was developed for the multi-targeted screening of biomarkers which aims at
      characterizing plant species in these supplements.

PMID- 22867545
TI  - New approaches for studying the chemical diversity of natural resources and the
      bioactivity of their constituents.
AB  - Natural products (NPs) have historically been an important source of lead
      molecules in drug discovery. However, the interest that the pharmaceutical
      industry has had in NPs has declined in part because of the lack of compatibility
      of traditional natural-product extract libraries with  high-throughput screenings
      and the low hit rate. Furthermore, in contrast to the synthetic libraries,
      compounds from natural sources are likely to have complex structures which slow
      down the identification process and contribute to problems related to supply and
      manufacturing. In this paper,  we summarise some of the strategies that are being
      developed in our research unit to address these issues. On one hand, differential
      screening strategies were established with the aim of identifying dynamically
      induced NPs from silent biosynthetic pathways in plants and fungi that had been 
      exposed to different stress situations. On the other hand, high-resolution HPLC
      techniques were optimised for biological and chemical profiling of crude
      extracts. This led to an integrated platform for rapid and efficient
      identification of new drug-leads and biomarkers of interest that were  based on
      miniaturised technological approaches and metabolomics.

PMID- 22867546
TI  - New insights in pharmaceutical analysis.
AB  - The research unit of pharmaceutical analytical chemistry (PAC) has been active in
      the field of separation sciences for many years. Liquid chromatography (LC) and
      its latest improvements such as ultra-high performance chromatography (UHPLC) and
      supercritical fluid chromatography (SFC)  are deeply and thoroughly studied, from
      a fundamental viewpoint to its various application capabilities. Electro-driven
      separations such as capillary electrophoresis (CE) are also a major field of
      interest, especially for macromolecules, and low cost. All these techniques are
      investigated  with various detection modes including mass spectrometry (MS) for
      various applications where high sensitivity and selectivity is needed. Extracting
      the relevant information from the overwhelming amount of data generated by modern
      analytical platforms has become an important issue for knowledge  discovery in
      various research fields. The appropriate treatment of such data is therefore of
      crucial importance to provide valuable information. Numerous works in our
      research group have demonstrated the usefulness of statistical and mathematical
      methodologies to improve quality of the results.  Therefore, well-established
      chemometric approaches (e.g. design of experiments, multivariate data analysis,
      etc.) are implemented to optimize the analytical process from method development
      to data analysis.

PMID- 22867547
TI  - The life sciences mass spectrometry research unit.
AB  - The Life Sciences Mass Spectrometry (LSMS) research unit focuses on the
      development of novel analytical workflows based on innovative mass spectrometric
      and software tools for the analysis of low molecular weight compounds, peptides
      and proteins in complex biological matrices. The present  article summarizes some
      of the recent work of the unit: i) the application of matrix-assisted laser
      desorption/ionization (MALDI) for mass spectrometry imaging (MSI) of drug of
      abuse in hair, ii) the use of high resolution mass spectrometry for simultaneous
      qualitative/quantitative analysis  in drug metabolism and metabolomics, and iii)
      the absolute quantitation of proteins by mass spectrometry using the selected
      reaction monitoring mode.

PMID- 22867548
TI  - LC-MS (/MS) in clinical toxicology screening methods.
AB  - Toxicological screening is the analysis of biological samples to detect and
      identify unknown compounds. The high selectivity and sensitivity of liquid
      chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry
      (MS/MS) technology provide an attractive alternative  to the current methods (LC
      UV, GC/MS, etc.). For these reasons, an increasing number of applications are
      being published. This paper is a brief overview of LC-MS(/MS) screening methods
      developed for clinical toxicology in recent years. Various sample treatments,
      chromatographic separations  and detection by mass spectrometry can be combined
      to obtain screening methods adapted to the constraints and needs of clinical
      toxicology laboratories. Currently the techniques are in the hands of
      specialists, mainly in academic institutions. However, the evolution in
      technology should allow  application of these techniques as a tool in toxicology
      laboratories, thus allowing a more widespread exploitation of their potential.

PMID- 22867549
TI  - Four windows on modern science in flavor and fragrance chemistry at Firmenich.
AB  - Four young scientists, recently hired by Firmenich, presented lectures at the
      University of Geneva. The objective was to stimulate young students to choose
      sciences. The challenges in the discovery, synthesis, or extraction of new
      molecules were presented, as well as the structure-activity  relationships of
      human odorant receptors.

PMID- 22867552
TI  - Thin-layer chromatography-nuclear magnetic resonance spectroscopy - a versatile
      tool for pharmaceutical and natural products analysisa.
AB  - Thin-layer chromatography (TLC) is a mature and very established technique,
      frequently used in many fields of applications ranging from natural product
      analysis to chemical or pharmaceutical applications. The introduction of a
      commercially available TLC-MS interface was a major  step complementing the ease
      of use of TLC with structural elucidation power of mass spectrometry (MS). The
      TLC-MS interface simplifies the workflow dramatically to gain structural
      information directly from TLC separations. This article describes the potential
      of TLC-nuclear magnetic resonance  spectroscopy (NMR) utilizing the TLC-MS
      interface to straightforwardly characterize zones of interest by NMR spectroscopy
      with a focus on quantification of active pharmaceutical ingredients (API) in
      formulations and identification of active principles in plant extracts.

PMID- 22867554
TI  - Intravenous iron replacement for persistent iron deficiency anemia after Roux-en
      Y gastric bypass.
AB  - BACKGROUND: Iron deficiency is a major postoperative complication of Roux-en-Y
      gastric bypass surgery. Oral replacement can fail to correct the deficiency.
      Thus, recourse to parenteral iron administration might be necessary. Our
      objective was to evaluate the effectiveness and safety of a standardized 2 g
      intravenous iron dextran infusion in the treatment of iron deficiency after Roux
      en-Y gastric bypass surgery. The setting was a university-affiliated community
      hospital in the United States. METHODS: We reviewed the medical records of 23
      patients at our institution who had received 2 g of iron dextran intravenously
      for recalcitrant iron deficiency after Roux-en-Y gastric bypass surgery. We
      obtained the demographic data and the complete blood count and serum iron studies
      obtained before treatment and at outpatient visits after infusion. RESULTS:
      Before treatment, all 23 patients were iron deficient (average ferritin 6 ng/mL)
      and anemic (average hemoglobin 9.4 g/dL). By 3 months, the average ferritin and
      hemoglobin had increased to 269 ng/mL and 12.3 g/dL, respectively. The hemoglobin
      levels remained stable throughout the follow-up period. The iron stores were
      adequately replaced in most patients. Four patients required a repeat infusion by
      1 year, because the ferritin levels had decreased to <15 ng/mL. The probability
      of remaining in an iron replete state was 84.6% (95% confidence interval 78
      91.2%). One patient required warm compresses for superficial phlebitis. No other
      significant adverse events were reported. CONCLUSION: Intravenous administration
      of 2 g of iron dextran corrects the anemia and repletes the iron stores for >=1
      year in most patients. This therapy is safe, tolerable, efficient, and effective.

PMID- 22867555
TI  - Anthropometric indexes outperform bioelectrical impedance analysis-derived
      estimates of body composition in identification of metabolic abnormalities in
      morbid obesity.
AB  - BACKGROUND: The validity of anthropometric indexes in ascertaining the body
      composition (BC) in morbidly obese (MO) subjects has been questioned. Our
      objective was to evaluate, in MO subjects, whether bioelectrical impedance
      analysis (BIA) of BC is more closely associated with the metabolic syndrome (MS)
      and insulin resistance (IR) than are classic anthropometric measurements. The
      setting was a university hospital. METHODS: The association between
      anthropometric (body mass index, waist circumference [WC]) and BIA (total fat
      mass [FM] [percentage of FM], truncal FM, android FM) estimates of BC, MS, and IR
      was evaluated in 784 white MO subjects (212 men and 572 women). BIA estimates
      were calculated using equations specific for MO subjects developed by our own
      group and validated against dual energy x-ray absorptiometry. RESULTS: The
      prevalence of the MS and IR was 78.6% and 88.6%, respectively. The body mass
      index was greater in women with the MS (P <.001) or IR (P <.001), and the WC was
      larger in subjects of both genders with the MS or IR (P <.001). Moreover, the WC
      correlated significantly with all the MS components (P <.05). In contrast, the
      percentage of FM, truncal FM, and android FM were significantly associated with
      the MS only in women. Stepwise logistic regression analysis demonstrated the WC
      as the only significant predictor of the MS or IR (both P <.001). Furthermore,
      receiver operating curve analysis showed WC was the most accurate BC parameter
      for the identification of subjects with the MS (area under the curve, WC = .681,
      P <.001) or IR (area under the curve, WC = .753, P <.001). CONCLUSION: In MO
      subjects, the BIA-derived indexes of total and central adiposity were not better
      predictors of the MS or IR than were traditional anthropometric measurements.

PMID- 22867556
TI  - Acute postgastric reduction syndrome.

PMID- 22867558
TI  - Sleeve gastrectomy and crural repair in obese patients with gastroesophageal
      reflux disease and/or hiatal hernia.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) with or without hiatal hernia
      (HH) is now recognized as an obesity-related co-morbidity. Roux-en-Y gastric
      bypass has been proved to be the most effective bariatric procedure for the
      treatment of morbidly obese patients with GERD and/or HH. In contrast, the
      indication for laparoscopic sleeve gastrectomy (SG) in these patients is still
      debated. Our objective was to report our experience with 97 patients who
      underwent SG and HH repair (HHR). The setting was a university hospital in Italy.
      METHODS: From July 2009 to December 2011, 378 patients underwent a preoperative
      workup for SG. In 97 patients, SG was performed with HHR. The clinical outcome
      was evaluated considering GERD symptom resolution or improvement, interruption of
      antireflux medications, and radiographic evidence of HH recurrence. RESULTS:
      Before surgery, symptomatic GERD was present in 60 patients (15.8%), and HH was
      diagnosed in 42 patients (11.1%). In 55 patients (14.5%), HH was diagnosed
      intraoperatively. The mean follow-up was 18 months. GERD remission occurred in 44
      patients (73.3%). In the remaining 16 patients, antireflux medications were
      diminished, with complete control of symptoms in 5 patients. No HH recurrences
      developed. "De novo" GERD symptoms developed in 22.9% of the patients undergoing
      SG alone compared with 0% of patients undergoing SG plus HHR. CONCLUSION: SG with
      HHR is feasible and safe, providing good management of GERD in obese patients
      with reflux symptoms. Small hiatal defects could be underdiagnosed at
      preoperative endoscopy and/or upper gastrointestinal contrast study. Thus, a
      careful examination of the crura is always recommended intraoperatively.

PMID- 22867559
TI  - Presidental address--Obesity discrimination: what can we do?

PMID- 22867560
TI  - Older adults adopted more cautious gait patterns when walking in socks than
      barefoot.
AB  - Walking barefoot or in socks is common for ambulating indoors and has been
      reported to be associated with increased risk of falls and related injuries in
      the elderly. This study sought to determine if gait patterns differed between
      these two conditions for young and older adults. A motion analysis system was
      used to record and calculate the stride characteristics and motion of the body's
      center of mass (COM) of 21 young and 20 older adults. For the walking tasks, the
      participants walked on a smooth floor surface at their preferred speed either
      barefoot or in socks in a random order. The socks were commercially available and
      commonly used. The results demonstrated that while walking in socks, compared
      with walking barefoot, older adults adopted a more cautious gait pattern
      including decreased walking speed and shortened stride length as well as reduced
      COM minimal velocity during the single limb support phase. Young adults, however,
      did not demonstrate significant changes. These findings suggest that walking with
      socks might present a greater balance threat for older adults. Clinically, safety
      precautions about walking in socks should be considered to be given to older
      adults, especially those with balance deficits.

PMID- 22867561
TI  - Vertical peak ground force in human infant crawling.
AB  - Quadrupedalism is a common mode of locomotion in land animals. The load
      distribution between the forelimbs (FL) and hindlimbs (HL) in quadrupedalism has
      been of great interest to researchers, and a database of the vertical peak force
      (Vpk) for FL and HL has been created for various species. However, Vpk in human
      infant crawling, a natural form of human quadrupedalism, has not been evaluated.
      We aimed to study Vpk in human infant crawling. Eight healthy infants who used a
      typical crawling style (i.e., crawling on the hands and knees) were included. The
      infants were encouraged to crawl over pressure mats placed on the floor, and Vpk
      of FL and HL were calculated. FL Vpk was 0.631+/-0.087 (per BW), and HL Vpk was
      0.638+/-0.089 (per BW). No significant difference was observed between FL and HL
      Vpk. The mean FL/HL Vpk ratio was -0.011 on a natural logarithmic scale. These
      data could be added to the current database on Vpk for quadrupedalism.

PMID- 22867562
TI  - Photoacoustic spectroscopy study of Blepharocalyx salicifolius (Kunt) O. Berg.
AB  - Photoacoustic spectroscopy (PAS) has revolutionized the fields of biological,
      environmental, and agricultural sciences. It is a very simple, sensitive, and non
      destructive technique that allows the determination of optical properties of bio
      samples. The in vivo chlorophylls of the leaf have a recorded maximum absorption
      peak at 675 nm as against 665 nm of the in vitro chlorophylls. The intensity of
      purple pigmentation in leaves of Blepharocalyx salicifolius (Kunt) O. Berg, is
      inversely correlated to the soil moisture levels, leaf water content and leaf
      water potentials. The applicability of PAS to biological samples was discussed.
      It allows the validation of existing emission models which are important for
      atmospheric process. A portable device for photoacoustic spectroscopy of plants
      and other photosynthetic tissues, cells and organelles is provided. Further,
      there is provided a method to measure photosynthesis of such tissues, cells and
      organelles.

PMID- 22867627
TI  - OSCILLATOR: A system for analysis of diurnal leaf growth using infrared
      photography combined with wavelet transformation.
AB  - BACKGROUND: Quantification of leaf movement is an important tool for
      characterising the effects of environmental signals and the circadian clock on
      plant development. Analysis of leaf movement is currently restricted by the
      attachment of sensors to the plant or dependent upon visible light for time-lapse
      photography. The study of leaf growth movement rhythms in mature plants under
      biological relevant conditions, e.g. diurnal light and dark conditions, is
      therefore problematic. RESULTS: Here we present OSCILLATOR, an affordable system
      for the analysis of rhythmic leaf growth movement in mature plants. The system
      contains three modules: (1) Infrared time-lapse imaging of growing mature plants
      (2) measurement of projected distances between leaf tip and plant apex (leaf tip
      tracking growth-curves) and (3) extraction of phase, period and amplitude of leaf
      growth oscillations using wavelet analysis. A proof-of-principle is provided by
      characterising parameters of rhythmic leaf growth movement of different
      Arabidopsis thaliana accessions as well as of Petunia hybrida and Solanum
      lycopersicum plants under diurnal conditions. The amplitude of leaf oscillations
      correlated to published data on leaf angles, while amplitude and leaf length did
      not correlate, suggesting a distinct leaf growth profile for each accession.
      Arabidopsis mutant accession Landsberg erecta displayed a late phase (timing of
      peak oscillation) compared to other accessions and this trait appears unrelated
      to the ERECTA locus. CONCLUSIONS: OSCILLATOR is a low cost and easy to implement
      system that can accurately and reproducibly quantify rhythmic growth of mature
      plants for different species under diurnal light/dark cycling.

PMID- 22867628
TI  - Tutorial on de novo peptide sequencing using MS/MS mass spectrometry.
AB  - This paper is a self-contained introductory tutorial on the problem in proteomics
      known as peptide sequencing using tandem mass spectrometry. This tutorial deals
      specifically with de novo sequencing methods (as opposed to database search
      methods). We first give an introduction to peptide sequencing, its importance and
      history and some background on proteins. Next we show the relationship between a
      peptide and the final spectrum produced from a tandem mass spectrometer, together
      with a description of the various sources of complications that arise during the
      process of generating the mass spectrum. From there we model the computational
      problem of de novo peptide sequencing, which is basically the reverse problem of
      identifying the peptide which produced the spectrum. We then present several
      major approaches to solve it (including reviewing some of the current algorithms
      in each approach), and also discuss related problems and post-processing
      approaches.

PMID- 22867629
TI  - Beware of moving targets: reference proteome content fluctuates substantially
      over the years.
AB  - Reference proteomes are generated by increasingly sophisticated annotation
      pipelines as part of regular genome build releases; yet, the corresponding
      changes in reference proteomes' content are dramatic. In the history of the NCBI
      curated human proteome, the total number of entries has remained roughly constant
      but approximately half of the proteins from the 2003 build 33 are no longer
      represented by entries in current releases, while about the same number of new
      proteins have been added (for sequence identity thresholds 50-90%). Although
      mostly hypothetical proteins are affected, there are also spectacular cases of
      entry removal/addition of well studied proteins. The changes between the 2003 and
      recent human proteomes are in a similar order of magnitude as the differences
      between recent human and chimpanzee proteome releases. As an application example,
      we show that the proteome fluctuations affect the interpretation (about 74% of
      hits) of organelle-specific mass-spectrometry data. Although proteome quality
      tends to improve with more recent releases as, for example, the fraction of
      proteins with functional annotation has increased over time, existing evidence
      implies that, apparently, the proteome content still remains incomplete, not just
      pertaining to isoforms/sequence variants but also to proteins and their families
      that are clearly distinct.

PMID- 22867631
TI  - Female newts (Taricha granulosa) produce tetrodotoxin laden eggs after long term
      captivity.
AB  - We investigated the presence of tetrodotoxin (TTX) in the eggs of wild-caught
      newts (Taricha granulosa) at capture and again after one, two, and three years in
      captivity. Females initially produced eggs that contained quantities of TTX
      similar to previous descriptions of eggs from wild-caught adults. After the first
      year in captivity, the egg toxicity from each female declined, ultimately
      remaining constant during each of the successive years in captivity. Despite
      declining, all females continued to produce eggs containing substantial
      quantities of TTX during captivity. The decline in toxicity can not be attributed
      to declining egg mass but may be the result of the abbreviated reproductive cycle
      to which the captive newts were subjected in the lab. Finally, an estimate of the
      amount of TTX provisioned in the entire clutch from each female is similar to the
      quantity of TTX regenerated in the skin after electrical stimulation. These
      results, coupled with other long-term studies on the maintenance and regeneration
      of TTX in the skin, suggests an endogenous origin of TTX in newts.

PMID- 22867630
TI  - Comparison of vildagliptin twice daily vs. sitagliptin once daily using
      continuous glucose monitoring (CGM): crossover pilot study (J-VICTORIA study).
AB  - BACKGROUND: No previous studies have compared the DPP-4 inhibitors vildagliptin
      and sitagliptin in terms of blood glucose levels using continuous glucose
      monitoring (CGM) and cardiovascular parameters. METHODS: Twenty patients with
      type 2 diabetes mellitus were randomly allocated to groups who received
      vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1
      month after starting each drug, and CGM was used to determine: 1) mean (+/-
      standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic
      excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood
      glucose level and time, 5) increase in blood glucose level after each meal, 6)
      area under the curve (AUC) for blood glucose level >=180 mg/dL within 3 hours
      after each meal, and 7) area over the curve (AOC) for daily blood glucose level
      <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5
      anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity
      (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1
      (PAI-1) levels, and urinary CPR levels, were measured. RESULTS: The mean 24-hour
      blood glucose level was significantly lower in patients taking vildagliptin than
      sitagliptin (142.1 +/- 35.5 vs. 153.2 +/- 37.0 mg/dL; p = 0.012). In patients
      taking vildagliptin, MAGE was significantly lower (110.5 +/- 33.5 vs. 129.4 +/-
      45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was
      significantly lower (206.1 +/- 40.2 vs. 223.2 +/- 43.5 mg/dL; p = 0.015), the AUC
      (>=180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9
      mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 +/-
      41.6 vs. 85.2 +/- 39.9 MUg/day; p = 0.008) than in patients taking sitagliptin.
      There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP,
      or PAI-1 levels between patients taking vildagliptin and sitagliptin.
      CONCLUSIONS: CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose
      level after supper, and hyperglycemia after breakfast were significantly lower in
      patients with type 2 diabetes mellitus taking vildagliptin than those taking
      sitagliptin. There were no significant differences in BNP and PAI-1 levels
      between patients taking vildagliptin and sitagliptin. TRIAL REGISTRATION:
      UMIN000007687.

PMID- 22867632
TI  - Multidimensional analyses to assess the relations between treatment choices by
      physicians and patients' characteristics: the example of COPD.
AB  - BACKGROUND: In some situations, practice guidelines do not provide firm evidence
      based guidance regarding COPD treatment choices, especially when large trials
      have failed to identify subgroups of particularly good or poor responders to
      available medications. METHODS: This observational cross-sectional study explored
      the yield of four types of multidimensional analyses to assess the associations
      between the clinical characteristics of COPD patients and pharmacological and non
      pharmacological treatments prescribed by lung specialists in a real-life context.
      RESULTS: Altogether, 2494 patients were recruited by 515 respiratory physicians.
      Multiple correspondence analysis and hierarchical clustering identified 6
      clinical subtypes and 6 treatment subgroups. Strong bi-directional associations
      were found between clinical subtypes and treatment subgroups in multivariate
      logistic regression. However, although the overall frequency of prescriptions
      varied from one clinical subtype to the other for all types of pharmacological
      treatments, clinical subtypes were not associated with specific prescription
      profiles. When canonical analysis of redundancy was used, the proportion of
      variation in pharmacological treatments that was explained by clinical
      characteristics remained modest: 6.23%. This proportion was greater (14.29%) for
      non-pharmacological components of care. CONCLUSION: This study shows that,
      although pharmacological treatments of COPD are quantitatively very well related
      to patients' clinical characteristics, there is no particular patient profile
      that could be qualitatively associated to prescriptions. This underlines
      uncertainties perceived by physicians for differentiating the respective effects
      of available pharmacological treatments. The methodology applied here is useful
      to identify areas of uncertainty requiring further research and/or guideline
      clarification.

PMID- 22867633
TI  - Antidepressant activity of Litsea glaucescens essential oil: identification of
      beta-pinene and linalool as active principles.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Litsea glaucescens (Lauraceae) has been used in
      Mexican Traditional Medicine to relieve illness related to central nervous
      system, such as epilepsy, fright and sadness. In this study, L. glaucescens
      essential oil properties on central nervous system were evaluated in mice using
      different behavioral tests. MATERIALS AND METHODS: The essential oil was obtained
      by hydrodistillation and analyzed by GC/MS. Identification of major compounds was
      also carried out by comparison with authentic samples. The psychopharmacological
      profile of L. glaucescens essential oil, and some its major compounds, were
      evaluated in mice using several experimental models: forced swimming test (FST:
      Antidepressant-like activity), open field test (OFT: Spontaneous locomotor
      activity), elevated plus-maze (EPM: Anxiolytic-like activity), exploratory
      cylinder (ECT: Sedative-like activity), rotarod (motor coordination) and traction
      performance (myo-relaxant effect) the essential oil and active principles was
      administered intraperitoneally. RESULTS: The essential oil showed antidepressant
      like activity at doses of 100 and 300 mg/Kg. The monoterpenes beta-pinene and
      linalool were identified as the two main active principles of the essential oil,
      and showed antidepressant-like and sedative-like activity. Eucalyptol, limonene
      and alpha-pinene they did not show antidepressant-like activity, and were not
      further tested. CONCLUSIONS: L. glaucescens essential oil showed antidepressant
      activity, beta-pinene and linalool were identified as its active principles.
      These results support the use of L. glaucescens in Mexican Traditional Medicine
      for the treatment of sadness.

PMID- 22867635
TI  - Antifungal activity in plants from Chinese traditional and folk medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: From over 100 Chinese clinical trial
      publications, we retrieved 22 commercial preparations and 17 clinical
      prescriptions used as Traditional Chinese Medicine (TCM) for treating mycotic
      vaginitis, typically caused by Candida albicans. The 8 most frequently used
      plants as well as another 7 TCM and 18 folk medicinal plants used in the South of
      China for antifungal therapy were investigated for in vitro antifungal activity.
      MATERIALS AND METHODS: For each plant we tested 4 extracts prepared with
      different solvents (water, ethanol, acetone, and n-hexane) for inhibition of
      Candida albicans and Saccharomyces cerevisiae growth in liquid culture. RESULTS:
      Some plants have quite strong antifungal activity, such as Tujinpi (Pseudolarix
      kaempferi Gord.), of which each extract could significantly inhibit the growth of
      both tested fungi. In addition, the acetone extract of Kushen (Sophora flavescens
      Ait.), the ethanol, acetone, and hexane extracts of Guanghuoxiang (Pogostemon
      cablin (Blanco) Benth.) and Gaoliangjiang (Alpinia officinarum Hance), the hexane
      extract of Dingxiang (Eugenia caryophyllata Thunb.), and the ethanol and acetone
      extracts of Kulianpi (Melia toosendan Sieb. et Zucc.) and Laliao (Polygonum
      hydropiper L.), all inhibited Candida albicans growth by more than 50%. In some
      cases growth inhibition was even comparable to that by the clinically used
      antifungal miconazole, which we used as our positive control. CONCLUSIONS: The
      majority of plants, whose clinical use for antifungal treatment is well supported
      within TCM or Chinese folk medicine, show in vitro antifungal activity against
      Candida albicans. Since Candida species represent the most common fungal pathogen
      of humans, these results provide more scientific evidence supporting the clinical
      application of these plants, and can serve as a starting point for new drug
      discovery from TCM and Chinese folk medicine.

PMID- 22867634
TI  - Antitumor activity and immunomodulatory effects of the intraperitoneal
      administration of Kanglaite in vivo in Lewis lung carcinoma.
AB  - AIMS OF THE STUDY: Kanglaite (KLT) is a useful antitumor drug with proven effects
      when combined with chemotherapy, radiotherapy or surgery. We hypothesize that KLT
      has antitumor activity and immunomodulatory effects in Lewis lung carcinoma.
      MATERIALS AND METHODS: C57BL/6 mice with Lewis lung carcinoma were divided into
      four groups: the control group (C), cisplatin group (1 mg/kg, DDP), low KLT group
      (6.25 ml/kg body weight [L]), and high KLT group (12.5 ml/kg body weight [H]). T
      cell proliferation was determined by the MTT assay. Nuclear factor-kappa B (NF
      kappaB), inhibitor kappa B alpha (IkappaBalpha), IkappaB kinase (IKK) and
      epidermal growth factor receptor (EGFR) levels were measured by western blotting.
      An enzyme-linked immunosorbent assay was used to analyze the expression of
      interleukin-2 (IL-2). RESULTS: Intraperitoneal KLT significantly inhibited the
      growth of Lewis lung carcinoma, and the spleen index was significantly higher in
      the L and H groups than in the C group. KLT stimulated T cell proliferation in a
      dose-dependent manner. Treatment with KLT at either 6.25 or 12.5 ml/kg decreased
      the level of NF-kappaB in the nucleus in a dose-dependent manner, and KLT
      markedly decreased the expression of IkappaBalpha, IKK and EGFR in the cytoplasm
      of tumor cells and overall. IL-2 was significantly increased in the supernatant
      of splenocytes in the H group. CONCLUSIONS: These results demonstrate that KLT
      has pronounced antitumor and immunostimulatory activities in C57BL/6 mice with
      Lewis lung carcinoma. These may affect the regulation of NF-kappaB/IkappaB
      expression, in addition to cytokines such as IL-2 and EGFR. Further work needs to
      investigate the relevant signaling pathway effects, but our findings suggest that
      KLT may be a promising antitumor drug for clinical use.

PMID- 22867636
TI  - Alcohol extract from Vernonia anthelmintica (L.) willd seed enhances melanin
      synthesis through activation of the p38 MAPK signaling pathway in B16F10 cells
      and primary melanocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia anthelmintica (L.) willd has been used
      in folk medicine to treat leukoderma in China for centuries. The promoting
      activities of its extract (AVE) in melanogenesis and possible signaling pathways
      were investigated in this article. MATERIALS AND METHODS: The improving
      activities of AVE were examined by melanin synthesis, tyrosinase activity assay
      and Western blot in B16F10 mouse melanoma cells and normal human primary
      melanocytes (NHMC). RESULTS: AVE increased the tyrosinase activity and melanin
      content in a dosage-dependent manner at concentrations of 1-40 MUg/ml and
      treatment with 20 MUg/ml AVE enhanced the expression of tyrosinase time
      dependently in both B16F10 cells and NHMC. Whether AVE affects the expression of
      microphthalmia-associated transcription factor (MITF), which is required for
      tyrosinase expression, was investigated. Our results showed that AVE induced MITF
      protein expression up-regulation. Besides, Western blot analysis revealed that
      AVE promoted the level of phosphorylation of p38 mitogen-activated protein kinase
      (p38 MAPK) markedly at 0-6 h, while the level of phosphorylation of CREB at 0-2
      h. The special p38 MAPK inhibitor, SB203580, and protein kinase A (PKA)
      inhibitor, H89, both attenuated the AVE-induced up-regulation of MITF and
      tyrosinase expression in B16F10 cells and NHMC. However, SB203580 could
      significantly decrease the melanin biosynthesis induced by AVE, but not H89.
      CONCLUSION: AVE exerts its improving effect on melanogenesis mainly by p38 MAPK
      activation and MITF induction of tyrosinase.

PMID- 22867637
TI  - Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with
      warfarin and aspirin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danshen-Gegen (DG) product has clinically been
      proven to be an effective agent for heart-tonic efficacy by our previous
      research. In the mean time, herb-drug interactions between DG product and its
      commonly co-administered drugs, such as aspirin or warfarin need to be explored
      to ensure its safe clinical usage. AIM OF THE STUDY: Current study aims to
      investigate whether DG extract interacts with warfarin or aspirin when
      administered concomitantly to ensure the safety and efficacy of their usage.
      MATERIAL AND METHODS: Five groups of SD rats (n=6/group) received DG alone (0.15
      g/kg, human relevant dose), warfarin alone (0.2 mg/kg), warfarin (0.2 mg/kg) in
      combination with DG (0.15 g/kg), aspirin alone (10.3 mg/kg), or aspirin (10.3
      mg/kg) in combination with DG (0.15 g/kg), respectively. DG product was given
      twice daily for 5 day. Warfain or aspirin were given once daily for 5 day. DG
      morning doses were given 2 h post that of warfarin/aspirin. Following first
      dosing on day 5, plasma samples were collected at different time points. For the
      pharmacodynamic measurement, whole blood was collected at 30 min after DG dosing
      or at 2.5 h after warfarin/aspirin dosing, and the prothrombin time assay was
      conducted. RESULTS: Co-administration of DG with warfarin could significantly
      decrease the C(max), AUC and the prothrombin time of warfarin (p<0.05). In the
      mean time, the C(max) and AUC of danshensu, the active bioavailable component of
      DG were significantly increased (p<0.01) in presence of warfarin. Co
      administration of DG with aspirin could significantly increase the C(max) and AUC
      of both aspirin (p<0.01) and its metabolite salicylic acid (p<0.01) and
      significantly decrease the prothrombin time of aspirin (p<0.05). However, the
      pharmacokinetics parameters of danshensu were not significantly affected by
      aspirin. CONCLUSION: Our animal study indicated that co-administration of DG with
      warfarin/aspirin can cause significant pharmacokinetic and pharmacodynamic herb
      drug interactions in rat.

PMID- 22867638
TI  - Antimicrobial activity of plants used as medicinals on an indigenous reserve in
      Rio das Cobras, Parana, Brazil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A considerable percentage of global biodiversity
      is located in Brazil, a country that also has rich cultural and ethnic diversity.
      In the community of Rio das Cobras, Parana, plants are still widely used in the
      health care not only by indigenous people but also by the non-indigenous
      population that inhabits the region. The investigation of the efficacy and safety
      of these plants in the treatment of infectious diseases provides insights for
      future studies of these species allowing the appropriated use by the indigenous
      people, since few or none study has been conducted so far. AIM OF THE STUDY:
      Evaluate the antimicrobial activity and cytotoxicity of some plants used as
      medicinal on an indigenous reserve in Rio das Cobras, Parana, Brazil. MATERIALS
      AND METHODS: The aqueous extracts were obtained by decoction and the 50% and 70%
      hydroalcoholic extracts by turbo extraction. The extracts were tested against
      strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa,
      Bacillus subtilis, Candida albicans, Candida parapsilosis, Candida tropicalis,
      Leishmania amazonensis, Poliovirus and HSV-1. Cytotoxicity assay using VERO cells
      were also performed. RESULTS: None of the extracts had a selectivity index (SI)>1
      for any of the tested bacteria. Only Campomanesia eugenioides and Schinus
      terebinthifolius had an SI>1.0 for all of the tested Candida species. The best
      anti-Leishmania activity was obtained with Zanthoxylum rhoifolium and Schinus
      terebinthifolius. Extracts of Cordia americana were the most effective against
      herpes simplex virus type 1. Zanthoxylum rhoifolium was the most effective
      against Poliovirus, and Ocimum gratissimum was effective against both Poliovirus
      and Herpes Simplex virus. Among the plants investigated in the present study,
      Zanthoxylum rhoifolium had the fewest cytotoxic effect. CONCLUSIONS: The plants
      investigated in the present study exhibited potential for future pharmacological
      uses, but additional studies, especially with regard to in vivo toxicity, must be
      conducted. The results of this preliminary survey are important for the Rio das
      Cobras Reserve community for the safe and effective use of plants in the
      treatment of some infectious diseases.

PMID- 22867639
TI  - Parking problem and negative cooperativity of binding of myosin subfragment 1 to
      F-actin.
AB  - Previously we provided evidence that myosin subfragment 1 (S1) can bind either
      one (state 1) or two actin monomers (state 2) in solution and in muscle fiber.
      Here we present results of the kinetics study of binding of S1 to F-actin labeled
      with fluorescent dye pyrene. A transition from state 1 to state 2 depends on
      probability that the second actin is free, which is high when molar ratio of
      S1/actin (R) is less than 0.5, and it decreases dramatically when R>2.0 due to
      the parking problem. The kinetics data obtained at different molar ratios were
      well fitted by two binding states model. The sequential binding of myosin head
      initially with one actin monomer and then with the second actin monomer in F
      actin can play a key role in force generation by actin-myosin and their directed
      movement.

PMID- 22867640
TI  - Supplemental cross-linking in tissue-based surgical implants for abdominal wall
      repair.
AB  - BACKGROUND: There are a number of commercially available tissue-based surgical
      implants for use in repairing abdominal wall defects. The role and effect of
      supplemental cross-linking present in some of these implants has been questioned
      and evaluated in a number of recent experiments. In this review we summarize
      results of preclinical animal studies evaluating tissue-based surgical implants
      used for abdominal wall repair with a focus on currently available products and
      the influence of supplemental cross-linking. METHODS: A search of PubMed, MEDLINE
      and article reference lists was undertaken. Inclusion criteria were animal
      studies, abdominal wall hernias, and studies reporting on the main outcomes of
      tensile strength, susceptibility to enzymatic degradation, antigenicity and
      immunogenicity, foreign body reaction, tissue ingrowth, and complications.
      Exclusion criteria included those studies that only reported on methods of
      fixation, implantation or fenestration of mesh. RESULTS: A total of 21 articles
      that specifically compared non-cross-linked and supplemental cross-linked tissue
      based implants were reviewed. In addition, other studies that compared tissue
      based implants, which are not commercially available, were included where
      appropriate. CONCLUSION: Supplemental cross-linking of collagen found in tissue
      based surgical implants has not been shown to adversely affect the strength of
      the implant or its ability to support long-term ingrowth of tissue. Further
      studies need to be performed to determine if the differences in cross-linked and
      non-cross-linked implants observed in animal models translate to differences in
      clinical performance.

PMID- 22867641
TI  - Lessons from the tip of the spear: medical advancements from Iraq and
      Afghanistan.
AB  - The conflicts in Iraq and Afghanistan have seen the advancement of combat
      medicine. The nature of the conflicts, with troops located in remote areas and
      faced with explosive ordinance designed to focus massive injuries on dismounted
      personnel, have forced military medical personnel to adapt accordingly. There has
      been a rekindling of interest in the use of tourniquets to stop exsanguination
      from extremity wounds, as well as in the transfusion of fresh whole blood from
      walking blood banks. These previously discarded techniques, born on battlefields
      long ago, have been refined and perfected and have led to an unprecedented
      survival for our wounded warriors. New developments in the field of applied
      hemostatic agents, damage control surgical techniques, and the implementation of
      an efficient evacuation system have also contributed to these results. The field
      of combat medicine has taken several concepts initially designed in civilian
      settings, such as temporary abdominal packing and vascular shunting, and adapted
      them to the military setting to provide state of the art trauma management to our
      troops in combat. In turn, developments in the resuscitation of the trauma
      patient, using increased blood and plasma products and less crystalloid, have
      been pioneered in conflict and transitioned to the civilian sector. Advancements
      made during the wars in Iraq and Afghanistan, as well as those still being
      developed, will shape the care of the injured patient, in both civilian and
      military settings, for the foreseeable future.

PMID- 22867642
TI  - Myths, misunderstandings, and dogma in respiratory care.
AB  - Evidence-based medicine has assumed a major place in establishing the standard of
      care for many diseases. Yet practices based largely on clinical experience have
      often been difficult to change, even when clearly associated with patient harm.
      In this paper, based on the 27th Philip Kittredge  Memorial Lecture, we highlight
      respiratory care practices that have clearly failed the tests of time and
      evidence yet sometimes tenaciously persist. We also discuss the appropriate use
      and potential abuse of evidence-based medicine.

PMID- 22867643
TI  - Aerosolized antibiotic therapy: a forward aerial assault or forced contingency
      for ventilator-associated pneumonia?

PMID- 22867644
TI  - Aerosol therapy in tracheotomized children: time for guidelines!

PMID- 22867645
TI  - Breath-actuated nebulizer versus small-volume nebulizer: efficacy, safety, and
      satisfaction.

PMID- 22867646
TI  - Is it asthma, COPD, or something in between, and does it matter?

PMID- 22867647
TI  - Noninvasive mechanical ventilation for prevention of post-extubation respiratory
      failure.

PMID- 22867648
TI  - Notice of retraction. Comparing performance of 3 oscillating positive expiratory
      pressure devices at similar amplitude and frequencies of oscillations on
      displacement of mucus inside trachea during cough.

PMID- 22867649
TI  - Risk of fracture after bariatric surgery in the United Kingdom: population based,
      retrospective cohort study.
AB  - OBJECTIVES: To estimate fracture risk in patients receiving bariatric surgery
      versus matched controls. DESIGN: Population based, retrospective cohort study.
      SETTING: Use of records from the United Kingdom General Practice Research
      Database, now known as the Clinical Practice Research Datalink (from January 1987
      to December 2010). PARTICIPANTS: Patients with a body mass index of at least 30,
      with a record of bariatric surgery (n=2079), and matched controls without a
      record (n=10,442). Each bariatric surgery patient was matched to up to six
      controls by age, sex, practice, year, and body mass index. Patients were followed
      from the date of bariatric surgery for the occurrence of any fracture. We used
      time dependent Cox regression to calculate relative rates of fracture, adjusted
      for disease and previous drug treatment, and time-interaction terms to evaluate
      fracture timing patterns. MAIN OUTCOME MEASURE: Relative rates of any,
      osteoporotic, and non-osteoporotic fractures. RESULTS: Mean follow-up time was
      2.2 years. Overall, there was no significantly increased risk of fracture in
      patients who underwent bariatric surgery, compared with controls (8.8 v 8.2 per
      1000 person years; adjusted relative risk 0.89, 95% confidence interval 0.60 to
      1.33). Bariatric surgery also did not affect risk of osteoporotic and non
      osteoporotic fractures. However, we saw a trend towards an increased fracture
      risk after three to five years following surgery, as well as in patients who had
      a greater decrease in body mass index after surgery, but this was not
      significant. CONCLUSION: Bariatric surgery does not have a significant effect on
      the risk of fracture. For the first few years after surgery, these results are
      reassuring for patients undergoing such operations, but do not exclude a more
      protracted adverse influence on skeletal health in the longer term.

PMID- 22867651
TI  - 21st century health services for an ageing population: 10 challenges for general
      practice.

PMID- 22867652
TI  - Medicines optimisation in primary care: can community pharmacies deliver?

PMID- 22867654
TI  - Integration of care: a bridge too far?

PMID- 22867653
TI  - Pharmacovigilance on the turn? Adverse reactions methods in 2012.

PMID- 22867655
TI  - Do GPs really provide 47 minutes a year for the patient?

PMID- 22867656
TI  - Leonardo da Vinci.

PMID- 22867657
TI  - Low-level exposure to carbon monoxide.

PMID- 22867658
TI  - Co-payments and a just health service.

PMID- 22867659
TI  - Substance misuse of gabapentin.

PMID- 22867660
TI  - Whose compass for morality?

PMID- 22867661
TI  - The GP's role in improving the uptake of healthy start vitamins.

PMID- 22867662
TI  - Telling the truth: why disclosure matters in chronic kidney disease.

PMID- 22867663
TI  - A new approach to patients with lower urinary tract symptoms.

PMID- 22867665
TI  - Health inequalities in primary care: time to face justice.

PMID- 22867673
TI  - Diagnosis and management of plantar fasciitis in primary care.

PMID- 22867674
TI  - Tips for GP trainees working in gastroenterology.

PMID- 22867675
TI  - A pharmacy medication alert system based on renal function in older patients.
AB  - BACKGROUND: Patients with diabetes or cardiovascular disease are at risk of
      reduced renal function and frequently use drugs that interact with renal
      function. GPs monitor renal function in these patients. Computerised prescription
      systems produce alerts in patients labelled as having chronic kidney disease, but
      alerts are often ignored. If pharmacists use a pharmacy medication alert system
      (PMAS) based on renal function, they can provide the GP with therapeutic advice
      to optimise the medication. The extent of this advice and the feasibility in the
      clinical context are unknown. AIM: To assess the therapeutic advice formulated by
      pharmacists with help of a PMAS based on the renal function of patients aged >=70
      years with diabetes or cardiovascular disease. DESIGN AND SETTING: Observational
      study in primary health care in the Netherlands. METHOD: GPs provided pharmacists
      with the renal function of older patients with diabetes or cardiovascular disease
      who were using target drugs, that is, drugs requiring therapeutic advice in
      patients with reduced renal function. With the help of a PMAS, pharmacists
      assessed the actual medication. The GP weighed the advice in relation to the
      clinical context of the individual patient. RESULTS: Six hundred and fifty
      patients were prescribed 1333 target drugs. Pharmacists formulated 143
      therapeutic recommendations (11% of target drugs) concerning 89 patients (13.7%
      of study population). In 71 recommendations in 52 patients (8.0% of study
      population), the GP agreed immediately. CONCLUSION: The use of a PMAS resulted in
      therapeutic advice in 11% of the target drugs. After weighing the clinical
      context, the GP agreed with half of the advice.

PMID- 22867676
TI  - Help needed in medication self-management for people with visual impairment: case
      control study.
AB  - BACKGROUND: Visual impairment (VI) is rising in prevalence and contributing to
      increasing morbidity, particularly among older people. Understanding patients'
      problems is fundamental to achieving optimal health outcomes but little is known
      about how VI impacts on self-management  of medication. AIM: To compare issues
      relating to medication self-management between older people with and without VI.
      DESIGN AND SETTING: Case-control study with participants aged >=65 years,
      prescribed at least two long-term oral medications  daily, living within the
      community. METHOD: The study recruited 156 patients with VI (best corrected
      visual acuity [BCVA] 6/18 to 3/60) at low-vision clinics; community optometrists
      identified 158 controls (BCVA 6/9 or better). Researchers visited participants in
      their homes,  administered two validated questionnaires to assess medication
      adherence (Morisky; Medication Adherence Report Scale [MARS]), and asked
      questions about medication self-management, beliefs, and support. RESULTS:
      Approximately half of the participants in both groups reported  perfect adherence
      on both questionnaires (52.5% Morisky; 43.3%, MARS). Despite using optical aids,
      few (3%) with VI could read medication information clearly; 24% had difficulty
      distinguishing different tablets. More people with VI (29%) than controls (13%)
      (odds ratio [OR] = 2.8; 95% confidence  interval [CI] = 1.6 to 5.0) needed help
      managing their medication, from friends (19% versus 10%) or pharmacists (10%
      versus 2.5%; OR = 4.4, 95% CI = 1.4 to 13.5); more received social service
      support (OR = 7.1; 95% CI = 3.9 to 12.9). CONCLUSION: Compared to their peers
      without  VI, older people with VI are more than twice as likely to need help in
      managing medication. In clinical practice in primary care, patients' needs for
      practical support in taking prescribed treatment must be recognised. Strategies
      for effective medication self-management should be explored.

PMID- 22867677
TI  - Hospital admissions from nursing homes: a qualitative study of GP decision
      making.
AB  - BACKGROUND: Decisions regarding the hospitalisation of nursing home residents may
      present a difficult dilemma for GPs. There are pressures to admit very frail
      patients with exacerbations of illness even though such frailty may limit the
      possible health gains. As 'gatekeepers' to NHS, GPs are expected to make best use
      of resources and may be criticised for 'inappropriate' admissions. Little is
      understood about the influences on GPs as they make such decisions. AIM: To
      explore GPs views on factors influencing decisions on admitting frail nursing
      home residents to hospital. DESIGN AND SETTING: A purposive sample of 21 GPs from
      two counties in the South of England. METHOD: Data from semi-structured, one-to
      one interviews with GPs were analysed using thematic analysis following
      principles of the constant comparative method. RESULTS: This study suggests that
      while clinical assessment, perceived benefits and risks of admission, and
      patients' and relatives' preferences are key factors in determining admissions,
      other important factors influencing decision making include medico-legal
      concerns, communications, capability of nursing homes and GP workload. These
      factors were also perceived by GPs as influencing the feasibility of keeping
      patients in the nursing home when this was clinically appropriate. Key areas
      suggested by GPs to improve practice were improving communication (particularly
      informational continuity), training and support for nursing staff, and peer
      support for GPs. Local initiatives to address these issues were very variable.
      CONCLUSION: Developing a systematic palliative care approach to address poor
      documentation and communication, the capability of nursing homes, and medico
      legal concerns has the potential to improve decision-making regarding hospital
      admissions.

PMID- 22867678
TI  - Difficulties in disclosing the diagnosis of dementia: a qualitative study in
      general practice.
AB  - BACKGROUND: Dementia is an insidious and stigmatised condition, and research
      indicates that GPs find communicating this diagnosis particularly problematic.
      Delays in diagnosis may impede optimal patient care. Little research has been
      published on Australian GPs' perceptions of barriers to disclosing the diagnosis
      of dementia. AIM: To explore GPs' perceptions of barriers to disclosing the
      diagnosis of dementia. DESIGN AND SETTING: Qualitative study in the general
      practice consultation context. METHOD: Semi-structured, audiorecorded interviews
      were conducted with GPs from three capital cities and one regional centre in
      Australia. Interviews were transcribed verbatim and thematic analysis was
      conducted. RESULTS: GPs' lack of confidence in having a correct diagnosis,
      concern to act in patients' best interests, and the stigma associated with the
      'dementia' label influenced the disclosure process. GPs found it challenging to
      identify dementia in the consultation context. It was difficult to raise the
      issue when both the patient and their family/carer(s) ignore/are unaware of
      symptoms of cognitive decline. Referral to a specialist was favoured to confirm
      suspicions, although this did not always result in a definitive diagnosis.
      Opinions differed as to whether the GP or the specialist was better placed to
      deliver the diagnosis. GPs preferred disclosure to the patient with his/her
      family/carer(s) present; associated issues of confidentiality and the importance
      of offering hope emerged. The severity of the patient's dementia also guided the
      diagnostic disclosure process. GPs often used euphemisms for dementia when
      disclosing the diagnosis, to soften the message. CONCLUSION: Complex issues
      surround the disclosure of dementia. Communicating this diagnosis remains
      particularly challenging for many GPs.

PMID- 22867679
TI  - Home visits for frail older people: a qualitative study on the needs and
      preferences of frail older people and their informal caregivers.
AB  - BACKGROUND: A number of studies have examined the effects of home visits and
      showed inconsistent results on physical functioning, institutionalisation, and
      mortality. Despite continuing interest from professionals in home visits for
      older people, reports on older people's  needs and preferences for such visits
      are scarce. AIM: This qualitative study aims to explore the views and needs of
      community-dwelling frail older people concerning home visits. DESIGN AND SETTING:
      A qualitative study including interviews with frail older  persons and their
      informal caregivers living in the area of Nijmegen, the Netherlands. METHOD: Semi
      structured interviews were conducted with frail older people and informal
      caregivers. A grounded theory approach was used for data-analysis. RESULTS:
      Eleven  frail older people and 11 informal caregivers were included. Most
      participants emphasised the importance of home visits for frail older people.
      They felt that it would give older people the personal attention they used to
      receive from GPs but miss nowadays. Most stated that this would give  them more
      trust in GPs. Participants stated that trust is one of the most important factors
      in a good patient-professional relationship. Further, participants preferred home
      visits to focus on the psychosocial context of the patient. They stated that more
      knowledge of the psychosocial  context and a good patient-professional
      relationship would enable the professional to provide better and more patient
      centred care. CONCLUSION: Patients' expectations of home visits are quite
      different from the actual purpose of home visiting programmes; that  is, care and
      wellbeing versus cure and prevention. This difference may partly explain why the
      effectiveness of home visits remains controversial. Future studies on home visits
      should involve patients in the development of home visiting programmes.

PMID- 22867680
TI  - Predictors of persistent complaints after a knee injury in primary care.
AB  - BACKGROUND: Prognosis of persistent complaints after knee injury is based on
      secondary care populations. In a primary care setting, however, no studies have
      addressed this issue. AIM: To identify possible predictors of persistent
      complaints 1 year after a knee injury. These predictors are important for guiding
      the GP's therapeutic management, and giving advice to patients about work and/or
      sports-related activities. DESIGN AND SETTING: Primary care prospective cohort
      study with a 1-year follow-up period in five municipalities in the southwest
      region of the Netherlands. METHOD: Patients who were eligible were recruited to
      the study by a GP research network with around 84,000 patients and 40
      participating GPs. A total of 134 patients (aged 18-65 years) who consulted their
      GP within 5 weeks after a knee injury entered the study. Follow-up after 1 year
      was conducted in 122 patients. The main outcome was persistent complaints 1 year
      after injury; possible predictors for these complaints were obtained with a
      questionnaire, a physical examination, and magnetic resonance imaging (MRI),
      according to a standardised protocol. RESULTS: After 1 year, of the 122 available
      patients, 21 (17%) reported persistent complaints and 101 (83%) reported full
      recovery or major improvement. In this study being aged >40 years had a
      significant association (P<0.05) with persistent complaints (odds ratio 8.0, 95%
      confidence interval 2.1 to 30.5). Physical examination and MRI findings revealed
      no predictors that were associated with these complaints. CONCLUSION: Being aged
      >40 years was the only determinant with a significant association with persistent
      complaints. As physical examination and MRI had no predictive value, they are not
      recommended for prognosis of persistent complaints.

PMID- 22867681
TI  - Do English patients want continuity of care, and do they receive it?
AB  - BACKGROUND: Interpersonal continuity of care is valued by patients, but there is
      concern that it has declined in recent years. AIM: To determine how often
      patients express preference for seeing a particular GP and the extent to which
      that preference is met. DESIGN OF STUDY: Analysis of data from the 2009/2010
      English GP Patient Survey. SETTING: A stratified random sample of adult patients
      registered with 8362 general practices in England (response rate 39%, yielding
      2,169,718 responses). METHOD: Weighted estimates were calculated of preference
      for and success in seeing a particular GP. Multilevel logistic regression was
      used to identify characteristics associated with these two outcomes. RESULTS:
      Excluding practices with one GP, 62% of patients expressed a preference for
      seeing a particular GP. Of these patients, 72% were successful in seeing their
      preferred GP most of the time. Certain patient groups were associated with more
      preference for and success in seeing a particular GP. These were older patients
      (preference odds ratio [OR] = 1.7, success OR = 1.8), those with chronic medical
      conditions (preference OR = 1.9, success OR = 1.3), those with chronic
      psychological conditions (preference OR = 1.6, success OR = 1.3), and those
      recently requesting only non-urgent versus urgent appointments (preference OR =
      1.4, success OR = 1.6). Patient groups that had more frequent preference but less
      success in seeing a preferred GP were females (preference OR = 1.5, success OR =
      0.9), patients in larger practices (preference OR = 1.3, success OR = 0.5), and
      those belonging to non-white ethnic groups. CONCLUSION: The majority of patients
      value interpersonal continuity, yet a large minority of patients and specific
      patient groups are not regularly able to see the GP they prefer.

PMID- 22867682
TI  - Patient centredness and the outcome of primary care consultations with patients
      with depression in areas of high and low socioeconomic deprivation.
AB  - BACKGROUND: Most patients with depression are managed in general practice. In
      deprived areas, depression is more common and poorer outcomes have been reported.
      AIM: To compare general practice consultations and early outcomes for patients
      with depression  living in areas of high or low socioeconomic deprivation. DESIGN
      AND SETTING: Secondary data analysis of a prospective observational study
      involving 25 GPs and 356 consultations in deprived areas, and 20 GPs and 303
      consultations in more affluent areas, with follow-up at  1 month. METHOD:
      Validated measures were used to (a) objectively assess the patient centredness of
      consultations, and (b) record patient perceptions of GP empathy. RESULTS: PHQ-9
      scores >10 (suggestive of caseness for moderate to severe depression)  were
      significantly more common in deprived than in affluent areas (30.1% versus 18.5%,
      P<0.001). Patients with depression in deprived areas had more multimorbidity
      (65.4% versus 48.2%, P<0.05). Perceived GP empathy and observer-rated patient
      centred communication were significantly  lower in consultations in deprived
      areas. Outcomes at 1 month were significantly worse (persistent caseness 71.4%
      deprived, 43.2% affluent, P = 0.01). After multilevel multiregression modelling,
      observer-rated patient centredness in the consultation was predictive of
      improvement in  PHQ-9 score in both affluent and deprived areas. CONCLUSION: In
      deprived areas, patients with depression are more common and early outcomes are
      poorer compared with affluent areas. Patient-centred consulting appears to
      improve early outcome but may be difficult to achieve  in deprived areas because
      of the inverse care law and the burden of multimorbidity.

PMID- 22867683
TI  - Ethnic differences in primary care management of diabetes and cardiovascular
      disease in people with serious mental illness.
AB  - BACKGROUND: Patients with serious mental illness (SMI) have high rates of
      cardiovascular disease (CVD). In contrast to widespread perception, their access
      to effective chronic disease management is as high as for the general population.
      However, previous studies have not included analysis by ethnicity. AIM: To
      identify differences in CVD and diabetes management, by ethnicity, among people
      with SMI. DESIGN AND SETTING: Three inner east London primary care trusts with an
      ethnically diverse and socially deprived population. Data were obtained from 147
      of 151 general practices. METHOD: Coded demographic and clinical data were
      obtained from GP electronic health records using EMIS Web. The sample used was
      the GP registered population on diabetes or CVD registers (52,620); of these,
      1223 also had SMI. RESULTS: The population prevalence of CVD and diabetes is
      7.2%; this rises to 18% among those with SMI. People with SMI and CVD or diabetes
      were found to be as likely to achieve clinical targets as those without SMI.
      Blood pressure control was significantly better in people with SMI; however, they
      were more likely to smoke and have a body mass index above 30 kg/m(2). Ethnic
      differences in care were identified, with south Asian individuals achieving
      better cholesterol control and black African or Caribbean groups achieving poorer
      blood pressure control. CONCLUSION: Risk factor management for those with SMI
      shows better control of blood pressure and glycosylated haemoglobin than the
      general population. However, smoking and obesity rates remain high and should be
      the target of public health programmes. Ethnic differences in management mirror
      those in the general population. Ethnic monitoring for vulnerable groups provides
      evidence to support schemes to reduce health inequalities.

PMID- 22867684
TI  - Restoring a sense of balance to NHS reform.

PMID- 22867685
TI  - Follow the yellow brick road: integrated care--can we do better?

PMID- 22867687
TI  - Association of bactericidal activity of genital tract secretions with Escherichia
      coli colonization in pregnancy.
AB  - OBJECTIVE: Genital tract secretions exhibit bactericidal activity against
      Escherichia coli. We hypothesized that this defense may be modulated during
      pregnancy. STUDY DESIGN: Secretions were collected by vaginal swab from 70
      pregnant women (35-37 weeks' gestation) and 35 nonpregnant controls. We mixed E
      coli with swab eluants or control buffer and colonies enumerated to measure
      bactericidal activity. Cytokines, chemokines, and antimicrobial peptides were
      quantified by multiplex or enzyme-linked immunosorbent assay. RESULTS: Pregnant
      women had significantly greater bactericidal activity, higher concentrations of
      proinflammatory cytokines, and lower levels of beta defensins compared to
      controls. Seven (10%) pregnant and 8 (23%) nonpregnant women were vaginally
      colonized with E coli; colonization was inversely associated with bactericidal
      activity. CONCLUSION: The soluble mucosal immune environment is altered in
      pregnancy. We speculate that the observed changes may protect against
      colonization and ascending infection and could provide a biomarker to identify
      pregnant women at risk for infectious complications including preterm birth.

PMID- 22867689
TI  - The effect of cardiopulmonary bypass prime volume on the need for blood
      transfusion after pediatric cardiac surgery.
AB  - OBJECTIVE: There is increasing awareness that erythrocyte transfusions after
      pediatric cardiac surgery have deleterious effects. Despite reports of decreased
      transfusion requirements associated with smaller cardiopulmonary bypass circuits,
      the relationship between circuit prime volume and need for transfusion has not
      been systematically examined. METHODS: Pediatric patients at our institution who
      underwent cardiopulmonary bypass between January 2005 and December 2010 were
      reviewed. Demographics, intraoperative data, and transfusion of packed red blood
      cells were retrospectively recorded. Cardiopulmonary bypass prime volume was
      indexed by patient body surface area. Logistic regression analysis was used to
      correlate these variables with need for transfusion. RESULTS: In the
      perioperative period, 1912 patients received transfusions and 266 did not. In
      univariate analysis, indexed prime volume was a significant predictor of
      transfusion (odds ratio, 1.007; P < .001). Other significant variables in
      univariate analysis included age, surgeon, Risk Adjustment for Congenital Heart
      Surgery 1 (RACHS-1) category, preoperative hemoglobin, total bypass time, aortic
      crossclamp time, use and duration of deep hypothermic circulatory arrest, lowest
      body core temperature, and cardiopulmonary bypass flow rate. Previous cardiac
      surgery was not a significant predictor. In multivariable analysis controlling
      for RACHS-1 category, surgeon, minimal core body temperature, and preoperative
      hemoglobin, indexed prime volume remained an independent predictor of transfusion
      (odds ratio, 1.006; 95% confidence interval, 1.005-1.007, P < .001). CONCLUSIONS:
      Perioperative need for transfusion in pediatric cardiac surgical patients is
      independently related to the prime volume of the cardiopulmonary bypass circuit.
      It therefore seems prudent to minimize circuit prime volumes to avoid unnecessary
      use of blood products.

PMID- 22867688
TI  - Transplacental transfer of vancomycin and telavancin.
AB  - OBJECTIVE: We sought to determine the bidirectional transfer and distribution of
      vancomycin and telavancin across the dually perfused term human placental lobule.
      STUDY DESIGN: The technique of dually perfused placental lobule was used in its
      recirculating mode to determine the maternal to fetal (M->F) (n = 20) and fetal
      to maternal (n = 18) transfer of each antibiotic, which were coperfused with
      their radioactive isotopes. The concentrations of drugs were determined by liquid
      scintillation spectrometry. RESULTS: In the M->F direction, the transfer of
      vancomycin (9.6 +/- 4%) and telavancin (6.5 +/- 2%) were low; however, telavancin
      retention by the perfused lobule was greater than that of vancomycin (P < .01).
      The normalized transplacental transfer of telavancin across the placental lobule
      in the fetal to maternal direction was higher than in the M->F direction (P <
      .01), suggesting the involvement of placental efflux transporters. CONCLUSION:
      The ex vivo perfusion experiments revealed low transfer of vancomycin and
      telavancin to the fetal circuit.

PMID- 22867690
TI  - WITHDRAWN: Distraction osteogenesis using monolateral external fixator for post
      traumatic skeletal defects of the femur.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22867691
TI  - Dose-response relationships of FMISO between trace dose and various macro-doses
      in rat by ultra-performance liquid chromatography with mass spectrometry and
      radioactivity analysis.
AB  - Screening the pharmacokinetics of candidates using liquid chromatography coupled
      to tandem mass spectrometry (LC-MS/MS) may be efficacious and safe for the
      research and development of new PET imaging agents. However, the PET imaging
      agent is administered as trace dose and the sensitivity of LC-MS/MS is often
      insufficient. If the dose was increased to be quantifiable, it should be
      necessary to prove whether the pharmacokinetics between trace and macro-doses is
      consistent or not. In this paper, fluoromisonidazole (FMISO), a tumor PET imaging
      agent, was chosen to evaluate the dose-response pharmacokinetics by administering
      various single intravenous doses (0.1, 0.4, 1.6 and 6.4 mg/kg) in male Sprague
      Dawley rats. The plasma concentration of FMISO was determined by an ultra
      performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method,
      and the blood radioactivity of [(18)F]FMISO was detected by a gamma counter. By
      calculating and comparing the pharmacokinetic parameters, the total area under
      the plasma concentration-time curve from time zero to infinity (AUC(0-infinity))
      and peak plasma concentration (C(max)) values increased with the selected FMISO
      doses, and showing linear dose-dependent. On the other hand, some parameters
      related to time, such as the elimination half-lives (t(1/2)) and elimination rate
      constant (K(e)) were dose-independent, and there is no significant deference
      between trace dose and various macro-doses. The data should be useful to evaluate
      the novel 2-nitroimidazole derivatives as potential PET tumor imaging agents.

PMID- 22867692
TI  - Analysis of serum IgE reactivity profiles with microarrayed allergens indicates
      absence of de novo IgE sensitizations in adults.

PMID- 22867693
TI  - Overall prevalence of self-reported food allergy in Canada.

PMID- 22867695
TI  - Selective elimination diet based on skin testing has suboptimal efficacy for
      adult eosinophilic esophagitis.

PMID- 22867694
TI  - Sleep and allergic disease: a summary of the literature and future directions for
      research.
AB  - Atopic diseases, such as asthma and allergic rhinitis, are common conditions that
      can influence sleep and subsequent daytime functioning. Children and patients
      with allergic conditions from ethnic minority groups might be particularly
      vulnerable to poor sleep and compromised daytime functioning because of the
      prevalence of these illnesses in these groups and the high level of morbidity.
      Research over the past 10 years has shed light on the pathophysiologic mechanisms
      (eg, inflammatory mediators) involved in many atopic diseases that can underlie
      sleep disruptions as a consequence of the presence of nocturnal symptoms.
      Associations between nocturnal symptoms and sleep and poorer quality of life as a
      result of missed sleep have been demonstrated across studies. Patients with
      severe illness and poor control appear to bear the most burden in terms of sleep
      impairment. Sleep-disordered breathing is also more common in patients with
      allergic diseases. Upper and lower airway resistance can increase the risk for
      sleep-disordered breathing events. In patients with allergic rhinitis, nasal
      congestion is a risk factor for apnea and snoring. Finally, consistent and
      appropriate use of medications can minimize nocturnal asthma or allergic symptoms
      that might disrupt sleep. Despite these advances, there is much room for
      improvement in this area. A summary of the sleep and allergic disease literature
      is reviewed, with methodological, conceptual, and clinical suggestions presented
      for future research.

PMID- 22867696
TI  - Initiation of angiogenesis in atherosclerosis: smooth muscle cells as mediators
      of the angiogenic response to atheroma formation.
AB  - Neovascularization of atherosclerotic lesions favors their progression toward
      rupture. Despite this pathophysiological importance, data regarding the
      mechanism(s) initiating plaque neovascularization are scarce. Recent findings
      indicate that smooth muscle cells located underneath early aortic atheromatous
      lesions display a pro-angiogenic phenotype, and that lipid mediators derived from
      these lesions are potent inducers of this phenotypic change. Here, we discuss
      these new data suggesting that smooth muscle cells could be the central
      organizers of an angiogenic response initiated by the very first cause of the
      atheromatous disease, the accumulation and retention of lipids in the arterial
      wall.

PMID- 22867697
TI  - Understanding the link between the placenta and future cardiovascular disease.
AB  - Inadequate placental development results in a number of untoward pregnancy
      outcomes, including pre-eclampsia, placental abruption and infarction, and fetal
      growth restriction and stillbirth. Although it was once assumed that these
      pregnancy-related complications caused only upfront maternal and fetal morbidity
      and mortality, poor placental development and function is now a well-recognized
      female-specific risk factor for future vascular morbidity and mortality. The
      epidemiological, genetic, and physiological research linking placental
      development and cardiovascular disease is growing, and this knowledge will
      undoubtedly not only translate into improved pregnancy outcomes for at-risk
      women, but also help to identify which women who had a complicated pregnancy
      could benefit from long-term follow-up and risk modification for cardiovascular
      disease. This article reviews the literature and provides suggestions for future
      follow-up of this vulnerable population of women.

PMID- 22867698
TI  - The expanding role of computed tomography in the assessment of coronary artery
      disease and cardiac anatomy.
AB  - There are increasing options for noninvasive tests to assess patients with chest
      pain syndromes or risk factors for atherosclerosis. Choosing the optimal test for
      an individual patient can be challenging. This review focuses on the expanding
      role of cardiac computed tomography (CT) and the rationale for its use in
      different patient groups. It also discusses which patients are best suited for
      cardiac CT and the necessary patient preparation.

PMID- 22867699
TI  - Fibroblast growth factor homologous factors in the heart: a potential locus for
      cardiac arrhythmias.
AB  - The four fibroblast growth factor homologous factors (FHFs; FGF11-FGF14) are
      intracellular proteins that bind and modulate voltage-gated sodium channels
      (VGSCs). Although FHFs have been well studied in neurons and implicated in
      neurologic disease, their role in cardiomyocytes was unclear until recently. This
      review discusses the expression profile and function of FHFs in mouse and rat
      ventricular cardiomyocytes. Recent data show that FGF13 is the predominant FHF in
      the murine heart, directly binds the cardiac VGSC alpha subunit, and is essential
      for normal cardiac conduction. FHF loss-of-function mutations may be unrecognized
      causes of cardiac arrhythmias, such as long QT and Brugada syndromes.

PMID- 22867700
TI  - Impaired angiogenesis in systemic sclerosis: the emerging role of the
      antiangiogenic VEGF(165)b splice variant.
AB  - Systemic sclerosis (SSc, or scleroderma) is a chronic, multisystem connective
      tissue disorder characterized by widespread microvascular damage, fibrosis, and
      autoimmunity that affects the skin and internal organs. In the course of SSc,
      chronic tissue ischemia and lack of compensatory angiogenesis may lead to loss of
      dermal capillaries and arterioles and severe peripheral vascular complications,
      such as nonhealing digital ulcers and, occasionally, gangrene of the extremities,
      which represent a heavy burden due to their major impact on patients' quality of
      life. Surprisingly, several studies published during the past decade showed that
      the potent proangiogenic mediator vascular endothelial growth factor-A (VEGF-A)
      is overexpressed in the skin and circulation of patients with SSc despite
      evidence of an overall insufficient angiogenic response. However, early studies
      could not make the distinction between proangiogenic VEGF(165) and antiangiogenic
      VEGF(165)b isoforms, which have been uncovered only recently and appear to be
      generated by alternative splicing mechanisms in the terminal exon of VEGF-A pre
      mRNA. In a recent study, we provided the first evidence that a switch from
      proangiogenic to antiangiogenic VEGF-A isoforms may play a crucial role in the
      defective angiogenic and vascular repair processes that characterize SSc. Future
      clinical and translational research should address whether molecular regulation
      of VEGF-A pre-mRNA splicing might represent a potential therapeutic strategy for
      the SSc-related peripheral vasculopathy and, most widely, for other pathologic
      conditions in humans in which we seek to promote or inhibit angiogenesis.

PMID- 22867702
TI  - Quality indicators for the design and implementation of simulation experiences: a
      Delphi study.
AB  - Simulation is widely used in nursing education. Previous studies have examined
      the impact of simulation on the acquisition of psychomotor skills, knowledge,
      critical thinking and non-technical skills such as teamwork. Challenges
      associated with the integration of simulation into nursing curricula have also
      been examined, however only limited research addresses the most effective
      simulation design and teaching strategies for quality educational outcomes. This
      paper reports a Delphi study that synthesises expert opinion on the pedagogical
      principles and teaching strategies that are indicative of quality in simulation
      based learning activities. The resultant set of Quality Indicator Statements is
      presented and opportunities for application and further research are discussed. 

PMID- 22867701
TI  - The relationship between pain and depressive symptoms after lumbar spine surgery.
AB  - Although depressive symptoms are common among those living with back pain, there
      is limited information on the relationship between postsurgical pain reduction
      and changes in depressive symptoms. The objective of this prospective cohort
      study was to examine the change in pain and depressive symptoms and to
      characterize the relationship between pain and depressive symptoms after lumbar
      spine surgery. We assessed 260 individuals undergoing lumbar spine surgery
      preoperatively and postoperatively (3 and 6 months) using a pain intensity
      numeric rating scale and the Patient Health Questionnaire depression scale. The
      relationship between change in pain (a 2-point decrease or 30% reduction from the
      preoperative level) and depressive symptoms was examined using standard
      regression methods. Preoperatively, the mean pain intensity was 5.2 (SD 2.4)
      points, and the mean depressive symptom score was 5.03 (SD 2.44) points. At 3
      months, individuals who experienced a reduction in pain (63%) were no more likely
      to experience a reduction in depressive symptoms (odds ratio 1.07, 95% confidence
      interval [CI] .58 to 1.98) than individuals who experienced no change from
      preoperative pain (34%). However, at 6 months, individuals who experienced a
      reduction in pain (63%) were nearly twice as likely to experience a reduction in
      depressive symptoms (odds ratio 1.93, 95% CI 1.15 to 3.25) as those who
      experienced no change or an increase in pain (31%). We found that most
      individuals experienced clinically important reductions in pain after surgery. We
      concluded that those whose pain level was reduced at 6 months were more likely to
      experience a reduction in depressive symptoms.

PMID- 22867703
TI  - Is reflective practice a qualitative methodology?

PMID- 22867704
TI  - AIMP3/p18 controls translational initiation by mediating the delivery of charged
      initiator tRNA to initiation complex.
AB  - Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs) are
      nonenzymatic scaffolding proteins that comprise multisynthetase complex (MSC)
      with nine aminoacyl-tRNA synthetases in higher eukaryotes. Among the three AIMPs,
      AIMP3/p18 is strongly anchored to methionyl-tRNA synthetase (MRS) in the MSC. MRS
      attaches methionine (Met) to initiator tRNA (tRNA(i)(Met)) and plays an important
      role in translation initiation. It is known that AIMP3 is dispatched to nucleus
      or nuclear membrane to induce DNA damage response or senescence; however, the
      role of AIMP3 in translation as a component of MSC and the meaning of its
      interaction with MRS are still unclear. Herein, we observed that AIMP3
      specifically interacted with Met-tRNA(i)(Met)in vitro, while it showed little or
      reduced interaction with unacylated or lysine-charged tRNA(i)(Met). In addition,
      AIMP3 discriminates Met-tRNA(i)(Met) from Met-charged elongator tRNA based on
      filter-binding assay. Pull-down assay revealed that AIMP3 and MRS had
      noncompetitive interaction with eukaryotic initiation factor 2 (eIF2) gamma
      subunit (eIF2gamma), which is in charge of binding with Met-tRNA(i)(Met) for the
      delivery of Met-tRNA(i)(Met) to ribosome. AIMP3 recruited active eIF2gamma to the
      MRS-AIMP3 complex, and the level of Met-tRNA(i)(Met) bound to eIF2 complex was
      reduced by AIMP3 knockdown resulting in reduced protein synthesis. All these
      results suggested the novel function of AIMP3 as a critical mediator of Met
      tRNA(i)(Met) transfer from MRS to eIF2 complex for the accurate and efficient
      translation initiation.

PMID- 22867705
TI  - Compaction of a prokaryotic signal-anchor transmembrane domain begins within the
      ribosome tunnel and is stabilized by SRP during targeting.
AB  - Cotranslational targeting of membrane proteins is mediated by the universally
      conserved signal recognition particle (SRP). In eukaryotes, SRP attenuates
      translation during targeting; however, in prokaryotes, a simplified SRP is
      believed to carry out targeting during continuing translation. Here, we show a
      detailed stepwise analysis of the targeting of subunit c of the F(0) component of
      the bacterial ATP synthase (F(0)c) to the inner membrane. We show that the first
      transmembrane (TM) signal-anchor domain of F(0)c forms a compacted structure
      within the distal portion of the ribosome tunnel. This structure is formed just
      prior to the interaction with SRP. In the absence of SRP this structure is lost
      as the TM domain exits the tunnel; however in the presence of SRP it is
      stabilized. Our results suggest differences in early protein folding of
      substrates for prokaryotic SRP-dependent membrane protein targeting pathways,
      from that of eukaryotic SRP targeting. These results imply that early TM domain
      recognition by targeting factors acts to ensure that the efficiency of membrane
      targeting is maintained.

PMID- 22867707
TI  - A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer
      cells.
AB  - The forward chemogenomics strategy allowed us to identify a potent cytotoxic
      thiazolidine compound as an apoptosis-inducing agent. Chemical structures were
      designed around a thiazolidine ring, a structure already noted for its anticancer
      properties. Initially, we evaluated these novel compounds on liver, breast, colon
      and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest
      cytotoxic activity (IC(50) ~5 MUM). Cell cycle analysis with ALC67 on liver cells
      revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that
      cytotoxicity of this compound was due to the activation of caspase-9 involved
      apoptotic pathway, which is death receptor independent.

PMID- 22867706
TI  - Twelve-month results of a paclitaxel releasing balloon in patients presenting
      with in-stent restenosis First-in-Man (PEPPER) trial.
AB  - BACKGROUND: Coronary in-stent restenosis (ISR) continues to be a therapeutic
      challenge especially after drug eluting stent (DES) implantation. We studied
      patients with ISR to investigate safety and efficacy of a novel drug coated
      balloon (DCB) incorporating paclitaxel into a microcrystalline structure by
      applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective
      First-in-Man trial. METHODS AND MATERIALS: Eighty-one patients were enrolled at 9
      European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and
      38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss
      (LLL) independently assessed by a quantitative coronary angiography laboratory at
      6 months. A secondary endpoint was major adverse cardiac events (MACE), a
      composite of cardiac death, non-fatal myocardial infarction, clinically driven
      target vessel revascularization after 6 and 12 months. RESULTS: At 6 months,
      overall LLL was 0.07+/-0.31 mm showing differences in BMS-ISR and DES-ISR
      treatment (-0.05+/-0.28 mm vs. 0.19+/-0.29 mm, respectively, P=.001). Overall
      MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one
      myocardial infarction, and no cardiac death nor stent thrombosis had occurred.
      CONCLUSION: Application of a novel paclitaxel coated balloon using BTHC as an
      excipient in patients with ISR is safe and results in very low LLL,
      revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov:
      NCT00961181).

PMID- 22867708
TI  - Stochastic searches and NMR experiments on four Lewis A analogues: NMR
      experiments support some flexibility around the fucosidic bond.
AB  - We have compared the conformational behavior of three Le(a) analogues with that
      of Le(a) using stochastic searches (MOE2005) and selective ROESY experiments. In
      the analogues either or both the beta-d-Gal and alpha-l-Fuc residues were
      replaced by beta-d-Glc and alpha-l-Rha units, respectively. All compounds showed
      similar behavior and even though four conformational families were identified,
      the calculations and NMR experiments support that the 'stacked conformation'
      known for Le(a) is predominant for all analogues. Interestingly, ROESY showed a
      correlation between H-1 Fuc/Rha and H-3 GlcNAc which, although small, could be
      seen in all analogues. For two compounds, the corresponding distance was measured
      and found to be shorter (~3.7A) than that found in the global minimum (4.5A).
      While one published study suggests some motion around the fucosidic bond, this
      constitutes the first experimental evidence supporting such flexibility. Our MD
      simulation (Amber10/Glycam06) on Le(a) was in full agreement with previous
      studies which described a rigid conformation for this branched trisaccharide.
      Thus, NMR seems to indicate that these dynamic studies are underestimating
      flexibility around the fucosidic bond.

PMID- 22867709
TI  - XIAP as a radioresistance factor and prognostic marker for radiotherapy in human
      rectal adenocarcinoma.
AB  - A differential responsiveness of patients to ionizing radiation is observed after
      preoperative radiotherapy for rectal adenocarcinoma that might be related, in
      part, to an apoptosis defect. To establish if proteins of the apoptotic cascades
      [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of
      apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor
      of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480)
      and radiosensitive (SW48) human colorectal cell lines. We demonstrated that,
      after irradiation, the SW48 cells increased the expression of the pro-apoptotic
      proteins, whereas the SW480 cells increased the expression of the anti-apoptotic
      protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and
      radiation-induced apoptotic index; the propensity of the SW480 cells to undergo
      apoptosis after radiation was higher compared with SW48 cells. In a translational
      study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for
      tumor and noncancerous tissue for each biopsy specimen using IHC. According to
      their response to preoperative radiotherapy, patients were classified into two
      groups: responsive and nonresponsive. Although no difference in expression of
      caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between
      responsive and nonresponsive patients, the ratio decreased for DIABLO and
      increased for XIAP. In conclusion, inhibition of XIAP rescues cellular
      radiosensitivity and both DIABLO and XIAP might be potential predictive markers
      of radiation responsiveness in rectal adenocarcinoma.

PMID- 22867710
TI  - Elevated expression of the chemokine-scavenging receptor D6 is associated with
      impaired lesion development in psoriasis.
AB  - D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for
      resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays
      a central role in controlling cutaneous inflammation, and that D6 deficiency is
      associated with development of a psoriasis-like pathology in response to varied
      inflammatory stimuli in mice. Examination of D6 expression in human psoriatic
      skin revealed markedly elevated expression in both the epidermis and lymphatic
      endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm
      distant from psoriatic plaques). Notably, this increased D6 expression is
      associated with elevated inflammatory chemokine expression, but an absence of
      plaque development, in uninvolved skin. Along with our previous observations of
      the ability of epidermally expressed transgenic D6 to impair cutaneous
      inflammatory responses, our data support a role for elevated D6 levels in
      suppressing inflammatory chemokine action and lesion development in uninvolved
      psoriatic skin. D6 expression consistently dropped in perilesional and lesional
      skin, coincident with development of psoriatic plaques. D6 expression in
      uninvolved skin also was reduced after trauma, indicative of a role for trauma
      mediated reduction in D6 expression in triggering lesion development.
      Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic
      patients, indicating that upregulation may be a general protective response to
      inflammation. Together our data demonstrate a novel role for D6 as a regulator of
      the transition from uninvolved to lesional skin in psoriasis.

PMID- 22867711
TI  - The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer
      disease is associated with dysfunction of the ubiquitin-proteasome system.
AB  - In Alzheimer disease (AD), deposition of neurofibrillary tangles and loss of
      synapses in the neocortex and limbic system each correlate strongly with
      cognitive impairment. Tangles are composed of misfolded hyperphosphorylated tau
      proteins; however, the link between tau abnormalities and synaptic dysfunction
      remains unclear. We examined the location of tau in control and AD cortices using
      biochemical and morphologic methods. We found that, in addition to its well
      described axonal localization, normal tau is present at both presynaptic and
      postsynaptic terminals in control human brains. In AD, tau becomes
      hyperphosphorylated and misfolded at both presynaptic and postsynaptic terminals,
      and this abnormally posttranslationally modified tau is enriched in
      synaptoneurosomal fractions. Synaptic tau seems to be hyperphosphorylated and
      ubiquitinated, and forms stable oligomers resistant to SDS denaturation. The
      accumulation of hyperphosphorylated tau oligomers at human AD synapses is
      associated with increased ubiquitinated substrates and increased proteasome
      components, consistent with dysfunction of the ubiquitin-proteasome system. Our
      findings suggest that synaptic hyperphosphorylated tau oligomers may be an
      important mediator of the proteotoxicity that disrupts synapses in AD.

PMID- 22867713
TI  - Loss of STAT6 promotes autoimmune disease and atopy on a susceptible genetic
      background.
AB  - Atopy and autoimmunity are usually considered opposed immunological
      manifestations. Lyn(-/-) mice develop lupus-like autoimmune disease yet have
      coexistent intrinsic allergic traits and are prone to severe, persistent asthma
      induced exogenously. Recently it has been proposed that the Th2 environment and
      IgE auto-Abs promotes autoimmune disease in Lyn(-/-) mice. To examine this
      apparent contradiction, we derived Lyn(-/-) mice with a null mutation in STAT6, a
      regulator of Th2 immunity that integrates signaling from the IL-4/IL-13 receptor
      complex. Atopy and spontaneous peritoneal eosinophilia, characteristic of Lyn(-/
      ) mice, were lost in young Lyn(-/-)STAT6(-/-) mice; however, autoimmune disease
      was markedly exacerbated. At a time-point where Lyn(-/-) mice showed only mild
      autoimmune disease, Lyn(-/-)STAT6(-/-) mice had maximal titres of IgG and IgA
      auto-Abs, impaired renal function, myeloid expansion and a highly activated T
      cell compartment. Remarkably, low level IgE auto-Abs but not IgG1 auto-Abs were a
      feature of some aged Lyn(-/-)STAT6(-/-) mice. Furthermore, aged Lyn(-/-)STAT6(-/
      ) mice showed dramatically increased levels of serum IgE but minimal IgG1,
      suggesting that class-switching to IgE can occur in the absence of an IgG1
      intermediate. The results show that Lyn-deficient mice can overcome the effects
      of disabling Th2 immunity, highlighting the importance of Lyn in controlling Th2
      responses. Our data also indicates that, under certain conditions, STAT6
      independent factors can promote IgE class-switching. This work has important
      clinical implications as many experimental therapies designed for the treatment
      of asthma or atopy are based on targeting the STAT6 axis, which could potentially
      reveal life endangering autoimmunity or promote atopy in susceptible individuals.

PMID- 22867712
TI  - Rheumatoid and pyrophosphate arthritis synovial fibroblasts induce
      osteoclastogenesis independently of RANKL, TNF and IL-6.
AB  - Bone destruction is a common feature of inflammatory arthritis and is mediated by
      osteoclasts, the only specialized cells to carry out bone resorption. Aberrant
      expression of receptor activator of nuclear factor kappa beta ligand (RANKL), an
      inducer of osteoclast differentiation has been linked with bone pathology and the
      synovial fibroblast in rheumatoid arthritis (RA). In this manuscript, we
      challenge the current concept that an increase in RANKL expression governs
      osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated
      human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis
      (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of
      their secreted factors to induce osteoclastogenesis. We determined a 10-fold
      increase of RANKL mRNA and protein in fibroblasts isolated from RA relative to
      PPA and OA patients. Peripheral blood mononuclear cells (PBMC) from healthy
      volunteers were cultured in the presence of RA, PPA and OA synovial fibroblast
      conditioned medium. Osteoclast differentiation was assessed by expression of
      tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), F-actin
      ring formation and bone resorption assays. The formation of TRAP(+), VNR(+)
      multinucleated cells, capable of F-actin ring formation and lacunar resorption in
      synovial fibroblast conditioned medium cultures occured in the presence of
      osteoprotegerin (OPG) a RANKL antagonist. Osteoclasts did not form in these
      cultures in the absence of macrophage colony stimulating factor (M-CSF). Our data
      suggest that the conditioned medium of pure synovial fibroblast cultures contain
      inflammatory mediators that can induce osteoclast formation in human PBMC
      independently of RANKL. Moreover inhibition of the TNF or IL-6 pathway was not
      sufficient to abolish osteoclastogenic signals derived from arthritic synovial
      fibroblasts. Collectively, our data clearly show that alternate osteoclastogenic
      pathways exist in inflammatory arthritis and place the synovial fibroblast as a
      key regulatory cell in bone and joint destruction, which is a hallmark of
      autoimmune arthritis.

PMID- 22867714
TI  - Resveratrol preserves myocardial function and perfusion in remote nonischemic
      myocardium in a swine model of metabolic syndrome.
AB  - BACKGROUND: Resveratrol has been shown to reverse some of the detrimental effects
      of metabolic syndrome (MetS). We sought to define the impact of supplemental
      resveratrol on normal myocardium remote from an ischemic territory in a swine
      model of MetS and chronic myocardial ischemia. STUDY DESIGN: Yorkshire swine were
      fed a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol
      diet with orally supplemented resveratrol (HCD-R; 100 mg/kg/day). Four weeks
      after diet modification, myocardial ischemia was induced by ameroid constrictor
      placement. Seven weeks later, myocardial tissue from a territory remote from the
      ischemia was harvested. Animals in the HCD and HCD-R groups underwent functional
      cardiac MRI before ischemia and before sacrifice. Tissue was harvested for
      protein expression analysis. RESULTS: After 7 weeks of ischemia, regional left
      ventricular systolic function was significantly increased in HCD-R as compared
      with HCD animals. During ventricular pacing the HCD group had significantly
      decreased flow (p = 0.03); perfusion in the HCD-R was preserved as compared with
      the control. There was no difference in microvascular relaxation. Expression of
      metabolic proteins Sirt-1 (p = 0.002), AMPkinase (p = 0.02), and carnitine
      palmitoyltransferase-I (p = 0.002) were upregulated in the HCD-R group. Levels of
      protein oxidative stress were significantly increased in the HCD and HCD-R
      groups, as compared with the controls (p = 0.003). Activated endothelial nitric
      oxide synthase (eNOS) was increased in the HCD-R group (p = 0.01). There was no
      difference in myocardial endothelial cell density between the groups; however,
      dividing endothelial cells were decreased in the HCD and HCD-R groups (p =
      0.006). CONCLUSIONS: Resveratrol supplementation improves regional left
      ventricular function and preserves perfusion to myocardium remote from an area of
      ischemia in an animal model of metabolic syndrome and chronic myocardial
      ischemia.

PMID- 22867715
TI  - Design and initial implementation of HerQLes: a hernia-related quality-of-life
      survey to assess abdominal wall function.
AB  - BACKGROUND: Success of a surgical intervention is often measured by hard clinical
      outcomes. In ventral hernia repair (VHR) these include wound morbidity and hernia
      recurrence. These outcomes fail to account for a surgical intervention's effect
      on a patient's quality of life (QofL). Our objective was to design a hernia
      specific QofL instrument with a focus on abdominal wall function, evaluate its
      measurement properties, and assess the impact of VHR on QofL using this new
      instrument. STUDY DESIGN: A 16-question QofL survey tool, HerQLes, was
      constructed. Patients presenting for elective VHR completed the survey. Rasch
      modeling was used to evaluate the items; fit statistics, person-item mapping,
      separation index, and reliability were examined. Associations between baseline
      characteristics and QofL were assessed. RESULTS: Eighty-eight patients completed
      the survey before assessment for VHR. Mean age was 57.2 years (+/-12.4 years),
      mean American Society of Anesthesiologists score was 2.8 (+/-0.5), and mean body
      mass index was 34.9 kg/m(2) (+/-9.3 kg/m(2)). Based on Rasch modeling, 12 of 16
      items met model fit criteria. The 4 poorly fitting items were eliminated from
      further analysis. The 12 items retained have good internal consistency
      reliability (0.86). On a 0- to 100-point scale, mean QofL score was 47.2 (+/
      15.6). Patients with higher grade hernias had lower HerQLes scores (p = 0.06).
      Patients showed significant improvement in abdominal wall function and QofL 6
      months after VHR (p < 0.01). CONCLUSIONS: Quality-of-life is an important
      component of surgical management of ventral hernias. The 12-question QofL survey,
      HerQLes, is reliable and valid. At baseline, patients with more complex hernias
      tended to have a decreased abdominal wall function and QofL. Six months after
      surgical repair, HerQLes scores change in the predicted direction. We believe
      HerQLes is potentially a valuable tool to assess patient-centered abdominal wall
      functional improvements after VHR.

PMID- 22867716
TI  - Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence
      population: a pilot study.
AB  - BACKGROUND: Marin County, CA has very high incidence of breast cancer.
      Traditional risk factors, such as those included in the Gail model, do not
      effectively stratify breast cancer in this population. This retrospective case
      control pilot study evaluates DNA from volunteers from a previous Marin County
      breast cancer epidemiology study. A polyfactorial risk model (OncoVue;
      InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5
      clinical risk factors was used to stratify risk in Marin County women. STUDY
      DESIGN: DNA genotyping was performed on 164 Caucasian women diagnosed with
      primary breast cancer in Marin County from 1997 to 1999 and 174 age- and
      ethnicity-matched control subjects. Individual lifetime risks were determined
      using the polyfactorial risk model and genotype frequencies in women at elevated
      risk were compared with the overall genotypes. RESULTS: The vitamin D receptor
      VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency
      in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR
      Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically
      significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes
      were also present, but in lower frequencies. CONCLUSIONS: The high frequency of
      the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk
      for breast cancer by the polyfactorial risk model might be related to the high
      incidence rates of breast cancer in Marin County, CA. Vitamin D supplementation
      could modify risk of breast cancer in this population.

PMID- 22867717
TI  - Outer membrane vesicles (OMV) production of Neisseria meningitidis serogroup B in
      batch process.
AB  - Serogroup B outer membrane vesicles (OMV) with iron regulated proteins (IRP) from
      Neisseria meningitidis constitute the antigen for the vaccine against the disease
      caused by this bacterium. Aiming to enhance final OMV concentration, seven batch
      experiments were carried out under four different conditions: (i) with original
      Catlin medium; (ii) with original Catlin medium and lactate and amino acids pulse
      at the 6th cultivation hour; (iii) with Catlin medium with double initial
      concentrations of lactate and amino acids and (iv) Catlin medium without glycerol
      and with double initial concentrations of lactate and amino acids. The
      cultivation experiments were carried out in a 7-L bioreactor under the following
      conditions: 36 degrees C, 0.5atm, overlay air 1L/min, agitation: 250-850 rpm, and
      O(2) control at 10%, 20 h. After lactate and amino acids exhaustion, cell growth
      reached stationary phase and a significant release increase of OMV was observed.
      According to the Luedeking & Piret model, OMV liberation is non-growth
      associated. Glycerol was not consumed during cultivation. The maximum OMV
      concentration value attained was 162 mg/L with correspondent productivity of
      8.1mg/(Lh) employing Catlin medium with double initial concentrations of lactate
      and amino acids. The obtained OMV satisfied constitution and protein pattern
      criteria and were suitable for vaccine production.

PMID- 22867718
TI  - Estimates of the annual direct medical costs of the prevention and treatment of
      disease associated with human papillomavirus in the United States.
AB  - Estimates of the direct medical costs attributable to human papillomavirus (HPV)
      can help to quantify the economic burden of HPV and to illustrate the potential
      benefits of HPV vaccination. The purpose of this report was to update the
      estimated annual direct medical costs of the prevention and treatment of HPV
      associated disease in the United States, for all HPV types. We included the costs
      of cervical cancer screening and follow-up and the treatment costs of the
      following HPV-associated health outcomes: cervical cancer, other anogenital
      cancers (anal, vaginal, vulvar and penile), oropharyngeal cancer, genital warts,
      and recurrent respiratory papillomatosis (RRP). We obtained updated incidence and
      cost estimates from the literature. The overall annual direct medical cost burden
      of preventing and treating HPV-associated disease was estimated to be $8.0
      billion (2010 U.S. dollars). Of this total cost, about $6.6 billion (82.3%) was
      for routine cervical cancer screening and follow-up, $1.0 billion (12.0%) was for
      cancer (including $0.4 billion for cervical cancer and $0.3 billion for
      oropharyngeal cancer), $0.3 billion (3.6%) was for genital warts, and $0.2
      billion (2.1%) was for RRP.

PMID- 22867719
TI  - Screening vaccine candidate strains against Streptococcus agalactiae of tilapia
      based on PFGE genotype.
AB  - The immunogenicity identification of epidemic strain is important for the
      development and application of vaccine. In this study, 85 Streptococcus
      agalactiae prevalent strains from the tilapia main cultured areas of China were
      distributed among 10 distinct PFGE genotypes (A-J). For each genotype, one
      representative strain (S.a(A)-S.a(J)) was selected to develop an inactivated
      whole-cell bacterial vaccine (V(A)-V(J)), which then underwent a protective
      immunity test. V(A)-V(J) showed similar relative percent survival (RPS) to the
      homologous or heterologous strains with the identical genotype, while the average
      RPS among V(A)-V(J) protecting against itself genotype strains showed large
      differences (44.71-98.81%). The RPS of V(A)-V(J) vaccinated fish against
      infections by the mixture of S.a(A)-S.a(J) at 15 days post vaccination (dpv) was
      ranged from 13.33% to 60.00%, and V(B), V(D), V(F), and V(G) showed the highest
      RPS of 60.00%, 46.67%, 53.33% and 60.00% respectively. V(B), V(D) and V(G) have
      their own specific protection scope, V(B) showed strong protective immunity to
      infections caused by A-D, F, G and J (53.57-100%), and V(G) showed strong
      protective immunity to C-H and J (50.00-100%), whereas V(D) showed weak
      protective immunity to all non-self genotype strains (14.81-36.67%). The results
      of the combined vaccination showed that V(G)+V(B) group had wider protection
      scope and higher RPS value than V(G)+V(D) group. Our results demonstrated that
      the protective immunity of S. agalactiae from tilapia was not only associated
      with their serotypes, but also related to their PFGE genotypes. It is difficult
      to acquire a single vaccine candidate strain that can protect against all
      genotype strains from the same serotype.

PMID- 22867720
TI  - Immune tolerance against HBV can be overcome in HBV transgenic mice by
      immunization with dendritic cells pulsed by HBVsvp.
AB  - In chronic Hepatitis B Virus (HBV) infection the function of dendritic cells
      (DC), T- and B-cells is impaired. DC vaccination is an option to overcome this.
      DC pulsed in vitro with HBV sub viral particles (HBVsvp) and used to immunize
      mice can activate HBV directed humoral and cellular immune responses. In the
      present study we vaccinated HBV transgenic mice as a model for chronic HBV
      infection and observed humoral and cellular immune responses. In these mice, the
      lacking immune response against HBV is mainly due to peripheral tolerance.
      HBVsvp, together with LPS as a co-activating molecule, were used for pulsing and
      in vitro activation of DC. HBV transgenic mice were injected with pulsed DC two
      times. Four weeks after DC vaccination humoral and cellular immune responses,
      viral antigen levels and liver histology were analyzed. DC vaccinated HBV
      transgenic mice developed a strong HBV specific antibody and T-cell response
      after DC vaccination. Neither circulating HBV antigen levels nor viremia,
      however, were controlled. No liver damage was observed. These results demonstrate
      that in vitro activation of DC and loading with HBVsvp can overcome tolerance
      against HBV and reactivate B- and T-cell responses in HBV transgenic mice, but
      were not sufficient to lead to virus control in these mice. Vaccination using DC,
      the key players of cellular and humoral immunity, after in vitro reactivation
      promises to break tolerance against HBV and may help patients with chronic
      hepatitis B to clear the infection.

PMID- 22867721
TI  - The epidemiology and risk factors for breakthrough varicella in Beijing Fengtai
      district.
AB  - Using data from the Immunization Information System (IIS) and the Infectious
      Disease Reporting System (IDRS), we have described the epidemiology and analyzed
      the risk factors for breakthrough varicella in the Fengtai district of Beijing,
      China. From 2008 to 2011 the breakthrough varicella infection rate (BVR) was
      0.65%, 0.85%, 1.08% and 1.56% respectively, thus demonstrating a distinct
      increasing tendency (P<0.001). We also compared the incidence of varicella
      related illnesses between the breakthrough varicella cases and unvaccinated
      cases, and found that the severity of illness in the breakthrough cases was
      milder than that of unvaccinated cases. Moderate-to-severe cases (P=0.008,
      OR=0.676, 95% CI=0.505-0.904) were differently distributed in the breakthrough
      varicella cases and unvaccinated cases. In this study, we demonstrated that
      floating status (P=0.031, OR=1.96, 95% CI=1.06-3.62), contact history (P<0.001,
      OR=2.67, 95% CI=1.59-4.69), time since vaccination (P=0.006, OR=1.59, 95% CI=1.14
      2.21), age at vaccination (P=0.010, OR=0.59, 95% CI=0.39-0.88) and combined
      vaccination (P=0.026, OR=3.99, 95% CI=1.18-13.54) were associated with the
      occurrence of breakthrough varicella, and among these, floating status is a novel
      risk factor. This study should provide useful information for the evaluation of
      the performance of varicella vaccination and prevention in PR China.

PMID- 22867722
TI  - Changes in seroprevalence to hepatitis A in Victoria, Australia: a comparison of
      three time points.
AB  - Serological data provide an important measure of past exposure and immunity to
      hepatitis A virus (HAV) infection in a population. National serosurveys from
      developed countries have typically indicated a decline in HAV seroprevalence over
      time as sanitation levels improve. We examined trends in the seroepidemiology of
      HAV antibodies in Victoria, Australia, drawing on cross-sectional samples taken
      at three time points over a 20-year period. Stored sera from 1988 (n=753), 1998
      (n=1091), and 2008 (n=791) from persons aged 1-69 years were obtained from the
      state of Victoria, Australia. The within-year population adjusted results show a
      significant trend of increasing population HAV seroprevalence over time from
      34.3% (95% CI 31.7-36.9) in 1988, to 40.0% (95% CI 37.1-42.8) in 1998 and 55.1%
      (95% CI 52.1-58.1) in 2008, P<0.0001. A particularly noticeable rise in
      population seroprevalence was observed between 1998 and 2008 for those aged 5-39
      years. The increase in HAV seropositivity over time is in contrast to the
      declining rates of disease notification in Australia. Based on comparisons with
      other Australian data, it appears the increase in population seroprevalence over
      the last two decades is unlikely to be due to endemic transmission of infection.
      Instead, other factors, including increases in travel to HAV endemic regions,
      migration to Australia from HAV endemic regions and vaccine uptake are more
      likely causes. Ongoing monitoring of serological HAV profiles in the population
      is required to determine future policy direction to prevent increased burden.

PMID- 22867723
TI  - A replication-incompetent virus possessing an uncleavable hemagglutinin as an
      influenza vaccine.
AB  - Vaccination is one of the most effective measures to protect against influenza
      virus infection. Inactivated and live-attenuated influenza vaccines are
      available; however, their efficacy is suboptimal. To develop a safe and more
      immunogenic vaccine, we produced a novel replication-incompetent influenza virus
      that possesses uncleavable hemagglutinin (HA) and tested its vaccine potential.
      The uncleavable HA was engineered by substituting the arginine at the C-terminus
      of HA1 with threonine, which prevents cleavage of HA into its HA1 and HA2
      subunits, preventing fusion between the host and viral membranes. Although this
      fusion-deficient HA influenza virus that possesses uncleavable HA (uncleavable HA
      virus) could undergo multiple cycles of replication in only wild-type HA
      expressing cells, it could infect normal cells and express viral proteins in
      infected cells, but could not generate infectious virus from infected cells due
      to the uncleavable HA. When C57BL/6 mice were intranasally immunized with the
      uncleavable HA virus, influenza-specific IgG and IgA antibodies were detected in
      nasal wash and bronchoalveolar lavage samples and in serum. In addition,
      influenza-specific CD8(+) T cells accumulated in the lungs of these mice.
      Moreover, mice immunized with the uncleavable HA virus were protected against a
      challenge of lethal doses of influenza virus, unlike mice immunized with a
      formalin-inactivated virus. These findings demonstrate that this fusion-deficient
      virus, which possesses uncleavable HA, is a suitable influenza vaccine candidate.

PMID- 22867724
TI  - Adverse cardiac events in patients with coronary stents undergoing noncardiac
      surgery: a systematic review.
AB  - BACKGROUND: When patients with drug-eluting stents (DES) present for surgery,
      current guidelines recommend delaying elective surgeries until 1 year of dual
      antiplatelet therapy has been completed. METHODS: We performed a systematic
      literature review of the major adverse cardiac events (MACE) associated with
      noncardiac surgery in patients with DES. RESULTS: Twenty-eight of 358 studies met
      inclusion criteria. Overall, MACE rates decreased as time to surgery increased
      and varied from 0% to 18% for surgeries within 1 year as compared with 0% to 12%
      for surgery more than 1 year after a stent. In addition, the current literature
      showed limited evidence for a protective effect of continuing perioperative dual
      antiplatelet therapy on MACE rates. CONCLUSIONS: The current literature supports
      a significant decrease in MACE when surgery is performed 1 year after DES
      placement; however, the level of evidence is weak. Larger studies are needed to
      determine the safe interval for surgery after stent placement.

PMID- 22867725
TI  - The Surgeons' Leadership Inventory (SLI): a taxonomy and rating system for
      surgeons' intraoperative leadership skills.
AB  - BACKGROUND: Surgeons must demonstrate leadership to optimize performance and
      maximize patient safety in the operating room, but no behavior rating tool is
      available to measure leadership. METHODS: Ten focus groups with members of the
      operating room team discussed surgeons' intraoperative leadership. Surgeons'
      leadership behaviors were extracted and used to finalize the Surgeons' Leadership
      Inventory (SLI), which was checked by surgeons (n = 6) for accuracy and face
      validity. The SLI was used to code video recordings (n = 5) of operations to test
      reliability. RESULTS: Eight elements of surgeons' leadership were included in the
      SLI: (1) maintaining standards, (2) managing resources, (3) making decisions, (4)
      directing, (5) training, (6) supporting others, (7) communicating, and (8) coping
      with pressure. Interrater reliability to code videos of surgeons' behaviors while
      operating using this tool was acceptable (kappa = .70). CONCLUSIONS: The SLI is
      empirically grounded in focus group data and both the leadership and surgical
      literature. The interrater reliability of the system was acceptable. The
      inventory could be used for rating surgeons' leadership in the operating room for
      research or as a basis for postoperative feedback on performance.

PMID- 22867726
TI  - Repair of incisional hernias with biological prosthesis: a systematic review of
      current evidence.
AB  - BACKGROUND: No consensus has been reached on the use of bioprosthetics to repair
      abdominal wall defects. The purpose of this systematic review was to summarize
      the outcomes from studies describing this use of various bioprosthetics for
      incisional hernia repair. METHODS: Studies published by October 2011 were
      identified through literature searches using EMBASE, MEDLINE, and the Cochrane
      Central Register of Controlled Trials. RESULTS: A total of 491 articles were
      scanned, 60 met eligibility criteria. Most studies were retrospective case
      studies. The studies ranged considerably in methodologic quality, with a modified
      Methodological Index of Nonrandomized Studies score from 5 to 12. Many repairs
      were performed in contaminated surgical sites (47.9%). At least one complication
      was seen in 87% of repairs. Major complications noted were wound infections
      (16.9%) and seroma (12.0%). With a mean follow-up period of 13.6 months the
      hernia recurrence rate was 15.2%. CONCLUSIONS: There is an insufficient level of
      high-quality evidence in the literature on the value of bioprosthetics for
      incisional hernia repair. Randomized controlled trials that use standardized
      reporting comparing bioprosthetics with synthetic mesh for incisional hernia
      repair are needed.

PMID- 22867727
TI  - Postpartum hemorrhage management in 2012: predicting the future.
AB  - Transfusion therapy in postpartum hemorrhage (PPH) traditionally has been modeled
      after precedents set in the Vietnam and Korean wars. However, data from recent
      military combat casualties suggest a different transfusion strategy. Transfusion
      of packed red blood cells, fresh frozen plasma, and platelets in a ratio of 1:1:1
      improves dilutional coagulopathy and survival. Women who present with low
      fibrinogen at the time of diagnosis of PPH have poorer outcomes and might benefit
      from early fibrinogen replacement. The antifibrinolytic agent, tranexamic acid,
      decreases bleeding and progression to severe PPH, but its role in PPH management
      is evolving. Observational data suggest that the use of recombinant factor VIIa
      should be limited to bleeding that has not responded to an optimal transfusion
      strategy. Point-of-care testing using thromboelastography is helpful in guiding
      the selection of blood products to be transfused. Additionally, massive
      transfusion protocols can decrease the overall number of products transfused and
      improve outcomes.

PMID- 22867728
TI  - Staphylococcal Cassette Chromosome mec type and antibiotic susceptibility
      profiles of vaginal and nonvaginal MRSA clinical isolates.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) causes nosocomial and
      community-associated infections, representing significant healthcare concerns.
      Limited studies have investigated cervicovaginal MRSA colonization and antibiotic
      susceptibility. Upon comparing clinical cervicovaginal MRSA isolates to
      nonvaginal isolates by Staphylococcal Cassette Chromosome mec type, presence of
      Panton-Valentine Leukocidin toxin, antibiotic susceptibility, and presence of
      associated resistance genes, no significant differences were observed between the
      anatomical sites, but were observed between our hospital- and community
      associated MRSA isolates. There was a significant increase in erythromycin
      resistance in our vaginal MRSA isolates compared to previous vaginal MRSA reports
      and an increase in clindamycin, doxycycline, and mupirocin resistance in our
      nonvaginal MRSA isolates compared to previously reported community-based skin and
      soft tissue MRSA isolates. Additionally, this is the first report of mupirocin
      resistance in vaginal MRSA isolates.

PMID- 22867729
TI  - Immunochromatographic assays for detection of Mycobacterium tuberculosis: what is
      the perfect time to test?
AB  - In this study, we aimed to correlate the analytical performance of SD BIOLINE TB
      Ag MPT64 Rapid Test kit (MPT64 assay) with the mycobacterial growth unit (GU)
      reported by the BACTEC MGIT 960 (MGIT 960) instrument. A total of 394 culture
      isolates reported positive by MGIT 960 were processed daily (until 'day 4') with
      the MPT64 assay until a positive MPT64 result was obtained and their GU values
      were noted daily before MPT64 testing. Based on this correlation of MPT64
      positivity and corresponding GU values, a GU cut-off was determined. In the
      validation phase, with the experimentally determined GU cut-off value, 99.1%
      (576/581) of culture isolates were correctly identified as MTB within 2 days from
      instrument positivity. All results were available using a single-MPT64 assay
      strip, making the assay cost-effective. Thus, systematic implementation of the
      MPT64 assay proved to be cost-effective in a high-throughput laboratory without
      any delay in patient reporting.

PMID- 22867730
TI  - Toscana meningoencephalitis: a comparison to other viral central nervous system
      infections.
AB  - BACKGROUND: Toscana virus (TOSV) is an emerging pathogen causing central nervous
      system (CNS) infection in Mediterranean countries, mostly during summer season.
      OBJECTIVES: To compare the clinical and laboratory characteristics of Toscana CNS
      infections to the most common viral pathogens seen in the United States. STUDY
      DESIGN: We performed a case series of patients with 41 TOSV infection and
      compared the clinical characteristics, laboratory findings, imaging results and
      clinical outcomes to the most commonly recognized viral causes of
      meningoencephalitis in the US [enterovirus (n=60), herpes simplex virus (n=48),
      and West Nile virus (n=30)] from our multi-center study of patients with aseptic
      meningoencephalitis syndromes in the Greater Houston area. RESULTS: TOSV
      infection occurs in different age groups compared to enterovirus, HSV, and WNV.
      All infections most frequently occur during summer-fall except HSV which
      distributes throughout the year. All patients with TOSV had history of travel to
      endemic areas. There are differences in clinical presentation and CSF findings
      comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant
      differences in outcomes of each infection except WNV meningoencephalitis which
      had a poorer outcome compared to TOSV infection. CONCLUSIONS: TOSV is an emerging
      pathogen that should be considered in the differential diagnosis of patients with
      CNS infections and a recent travel history to endemic areas.

PMID- 22867731
TI  - Neurodevelopmental anomalies of the hippocampus in rats exposed to weak intensity
      complex magnetic fields throughout gestation.
AB  - There has been increasing interest on the possible harmful effects of prenatal
      exposure to magnetic fields. To investigate the effect of weak intensity magnetic
      fields on the prenatal brain, pregnant Wistar rats were continuously exposed to
      one of four intensities (reference: 5-20 nT; low 30-50 nT; medium 90-580 nT; high
      590-1200 nT) of a complex magnetic field sequence designed to interfere with
      brain development. As adults, rats exposed to the low-intensity (30-50 nT)
      complex magnetic field displayed impairments in contextual fear learning and
      showed anomalies in the cytological and morphological development of the
      hippocampus. In particular, low-intensity exposures resulted in a reduction in
      overall hippocampal size and promoted subtle dysgenesis of the CA1 and CA3
      regions. In contrast, exposure to weaker or stronger intensities of the same
      complex magnetic field pattern did not interfere with hippocampal development or
      fear behavior. These findings suggest that prenatal exposure to complex magnetic
      fields of a narrow intensity window during development can result in subtle but
      permanent alterations in hippocampal microstructure and function that can have
      lasting effects on behavior.

PMID- 22867732
TI  - Functional implications of hypothalamic neurogenesis in the adult mammalian
      brain.
AB  - Adult neurogenesis represents a striking example of structural plasticity in the
      mature brain. Research on adult mammalian neurogenesis today focuses almost
      exclusively on two areas: the subgranular zone (SGZ) in the dentate gyrus of the
      hippocampus, and the subventricular zone (SVZ) of the lateral ventricles.
      Numerous studies, however, have also reported adult neurogenesis in the
      hypothalamus, a brain structure that serves as a central homeostatic regulator of
      numerous physiological and behavioral functions, such as feeding, metabolism,
      body temperature, thirst, fatigue, aggression, sleep, circadian rhythms, and
      sexual behavior. Recent studies on hypothalamic neurogenesis have identified a
      progenitor population within a dedicated hypothalamic neurogenic zone.
      Furthermore, adult born hypothalamic neurons appear to play a role in the
      regulation of metabolism, weight, and energy balance. It remains to be seen what
      other functional roles adult hypothalamic neurogenesis may play. This review
      summarizes studies on the identification and characterization of neural
      stem/progenitor cells in the mammalian hypothalamus, in what contexts these
      stem/progenitor cells engage in neurogenesis, and potential functions of
      postnatally generated hypothalamic neurons.

PMID- 22867733
TI  - Enteric neurons from postnatal Fgf2 knockout mice differ in neurite outgrowth
      responses.
AB  - The enteric nervous system (ENS) consists of several neuronal subclasses with
      distinct functional properties. The formation and maintenance of these distinct
      populations during development and aging is dependent on the support of
      appropriate neurotrophic factors. During early postnatal development, the ENS has
      to adept continuously to changing alimentation situations, which might also
      affect neuronal maturation and differentiation. There is evidence that basic
      fibroblast-growth-factor (Fgf2) exerts neurotrophic effects in the ENS. In this
      study primary myenteric plexus cultures from both wild type and Fgf2-knockout
      mice were investigated under the influence of Fgf2 and glial-cell-line-derived
      factor (GDNF). It could be demonstrated, that the influence of neurotrophic
      support is decreased in the Fgf2-knockouts, while the neuronal cultures of wild
      type revealed a more pronounced receptiveness for trophic support. These data
      show that Fgf2 plays a role in the development of the ENS.

PMID- 22867734
TI  - Epidemiology and outcome of burns: early experience at the country's first
      national burns centre.
AB  - This study aims to document the epidemiologic pattern and outcome of burn
      injuries in the country's first national burn centre. This case series study was
      conducted over a 2-year period at Burns Care Centre (BCC), Pakistan Institute of
      Medical Sciences (PIMS), Islamabad. The study included all burn injury patients
      who primarily presented to and were managed at the centre. Those patients who
      presented more than 24 h after injury or those who were initially managed at some
      other hospital were excluded from the study. Initial assessment and diagnosis was
      made by thorough history, physical examination and necessary investigations.
      Patients with major burns, high voltage electric burns and those needing any
      surgical interventions were admitted for indoor management. Patients with minor
      burns were discharged home after necessary emergency management, home medication
      and follow-up advice. The sociodemographic profile of the patients, site of
      sustaining burn injury, type and extent (total body surface area (TBSA), skin
      thickness involved and associated inhalational injury) of burn and outcome in
      terms of survival or mortality, etc., were all recorded on a proforma. The data
      were subjected to statistical analysis. Out of a total of 13,295 patients, there
      were 7503 (56.43%) males and 5792 (43.56%) females. The mean age for adults was
      33.63+/-10.76 years and for children it was 6.71+/-3.47 years. The household
      environment constituted the commonest site of burns (68%). Among all age groups
      and both genders, scalds were the commonest burns (42.48%), followed by flame
      burns (39%) and electrical burns (9.96%). The affected mean TBSA was 10.64+/
      11.45% overall, while for the hospitalised subset of patients the mean TBSA was
      38.04+/-15.18%. Most of the burns were partial thickness (67%). Inhalation injury
      was found among 149 (1.12%) patients. Most of the burns were non-intentional and
      only 96 (0.72%) were intentional. A total of 1405 patients (10.58%) were admitted
      while the remainder 11890 patients (89.43%) were managed on an outdoor basis. The
      mean hospital stay was 12.16+/-6.07 days (range 2-73 days). There were 197 deaths
      among the hospitalised patients constituting a 14% mortality rate for the
      hospitalised subset of patients, while there was an overall mortality rate of
      1.48% for the entire study population.

PMID- 22867735
TI  - Individualised vancomycin doses for paediatric burn patients to achieve PK/PD
      targets.
AB  - BACKGROUND: The objective of the study was to investigate vancomycin dose
      adjustment in pediatric burn patients by evaluating trough drug concentrations
      and the pharmacokinetic and pharmacodynamic (PK/PD) correlation. METHODS: Study
      subjects included 13 patients who were 6.0 years old, 25 kg (median). with normal
      renal function. These had at least a 30% total burn surface area and inhalation
      injury were present in 7/13 patients. The patients were investigated
      prospectively. Plasma monitoring and PK assessments were performed by serial
      blood sample collections (30 sets). Only 0.2 mL of each plasma sample was
      required for our plasma measurements, which were made by high performance liquid
      chromatography. The vancomycin PK/PD target was set at AUC0-24(ss)/MIC>400.
      RESULTS: Trough values less than 10 MUg/mL were obtained in 16/30 sets (53%) as a
      consequence of increased plasma clearance and the apparent volume of
      distribution. The daily dose was subsequently increased from 43.4 +/- 9.0mg/kg
      (mean +/- SD) to 98.0 +/- 17.9 mg/kg, p<0.05. The PK/PD target was reached for
      pathogens with 0.5mg/L, 1mg/L, 2mg/L and 4 mg/L MIC in 93.3% (28/30), 66.7%
      (20/30), 33.3% (10/30) and 3.3% (1/30) of the sets, respectively. CONCLUSIONS: To
      more rapidly achieve the PK/PD targets in pediatric burn patients with normal
      renal function, an initial dose of approximately 90-100mg/kg/day is recommended;
      however, this higher dosage regimen should be further evaluated in this
      population in terms of efficacy and toxicity as well as in terms of achieving
      pharmacodynamic goals.

PMID- 22867736
TI  - Vulvar intraepithelial neoplasia (VIN 2/3): comparing clinical outcomes and
      evaluating risk factors for recurrence.
AB  - OBJECTIVE: To evaluate demographic and clinical characteristics associated with
      the development of vulvar intraepithelial neoplasia (VIN 2/3), and factors
      associated with recurrence. METHODS: A retrospective chart review of 303 patients
      with VIN 2/3 evaluated at a single institution between 1993 and 2011 was
      performed. Medical records were reviewed for demographic information, risk
      factors, treatment type, pathologic diagnosis, and recurrence/outcome
      information. RESULTS: Median age at diagnosis was 47 years (range 14-87). 40% of
      patients reported current tobacco use and 26% reported previous use. Primary
      treatment included excision (n=176, 59%), laser ablation (n=40, 13%), imiquimod
      (n=22, 7.4%), excision with laser (n=24, 8.1%), excision with imiquimod (n=10,
      3.4%), and laser with imiquimod (n=3, 1.0%). 92 patients (62.6%) were noted to
      have positive margins, which was associated with larger tumor size (p=0.004). 87
      patients (28.7%) developed recurrent disease, which was associated with smoking
      (p<0.001), larger lesion size (p=0.016), and positive margins (p=0.005). On
      univariate analysis, higher rates of recurrence were associated with laser
      ablation (45.0%) compared with excision (26%) or imiquimod (13.6%) (p=0.018).
      However, on multivariate analysis of recurrence-free survival (RFS) these
      therapies were equivalent when used individually, but the use of excision plus
      laser had an adverse impact on RFS (p<0.001). 7 patients (2.3%) recurred with
      invasive disease a median of 109 months (range 12-327) from initial VIN 2/3
      diagnosis. CONCLUSIONS: This large cohort of women with VIN 2/3 further
      delineates the demographic and clinical factors associated with VIN 2/3. High
      rates of recurrence were noted and found to be associated with smoking, larger
      lesion size, and positive margins. While higher rates of recurrence were found
      among those treated with laser ablation, it was not inferior with respect to RFS
      when used alone, but the use of laser with excision was associated with decreased
      RFS. Our findings provide hypothesis-generating material for further research in
      the management of VIN2/3.

PMID- 22867737
TI  - An experimental analysis of disgust sensitivity and fear of contagion in Spider
      and Blood Injection Injury Phobia.
AB  - Disgust sensitivity and concern with contamination have been frequently
      associated with Spider and Blood-Injection-Injury (BII) Phobias. This study
      assessed the domain specificity of disgust sensitivity and concern with
      contamination in 29 Non-Phobic Controls, 25 clinical Spider Phobics, 26 clinical
      BII Phobics, and 27 persons who met clinical criteria for Spider Phobia and BII
      Phobia. On self-report measures we found evidence of domain specificity of
      disgust sensitivity for the Spider and BII Phobia groups. Furthermore, we found
      that persons with both phobias may be more disgust sensitive than persons with a
      single phobia. Interestingly, the animal reminder disgust stimulus used in this
      research was more sensitive to detecting domain specific differences in disgust
      sensitivity between Phobic groups than was the core disgust stimulus, emphasizing
      the importance of developing standardized behavioral measures of disgust
      sensitivity in future research. Lastly, findings from this research suggest that
      concern with contamination may be more influential in phobic avoidance for
      persons with Spider Phobia than for persons with BII Phobia. Treatment
      implications for these findings are discussed.

PMID- 22867738
TI  - Microcirculation in the healing of surgical wounds in the oral cavity.
AB  - The aim of this research is to evaluate in vivo the characteristics of
      microcirculation after taking a biopsy sample from the oral mucosa. 20 patients
      were recruited to the study and all underwent an oral mucosa biopsy for the
      excision of benign neoformations. The modifications in the oral microcirculation
      were evaluated in vivo in correspondence to the surgical site through
      videocapillaroscopy at three different times: 30 min before the biopsy; 48 h
      after the biopsy; and 7 days after the biopsy. The statistical significance was
      checked with the Mann-Whitney U-test (P<0.05). The analysis of
      videocapillaroscopic patterns showed statistically significant variations
      relative to the capillary loop density; the diameter of the outgoing loop; and
      the length of the capillary loop. In conclusion, the study describes a simple and
      reproducible model for the study of wound healing from a microcirculatory point
      of view.

PMID- 22867739
TI  - Effects of the 3D bone-to-implant contact and bone stiffness on the initial
      stability of a dental implant: micro-CT and resonance frequency analyses.
AB  - This study investigated the effects of bone stiffness (elastic modulus) and three
      dimensional (3D) bone-to-implant contact ratio (BIC%) on the primary stabilities
      of dental implants using micro-computed tomography (micro-CT) and resonance
      frequency analyses. Artificial sawbone models with five values of elastic modulus
      (137, 123, 47.5, 22, and 12.4 MPa) comprising two types of trabecular structure
      (solid-rigid and cellular-rigid) were investigated for initial implant stability
      quotient (ISQ), measured using the wireless Osstell resonance frequency analyzer.
      Bone specimens were attached to 2 mm fibre-filled epoxy sheets mimicking the
      cortical shell. ISQ was measured after placing a dental implant into the bone
      specimen. Each bone specimen with an implant was subjected to micro-CT scanning
      to calculate the 3D BIC% values. The similarity of the cellular type of
      artificial bone to the trabecular structure might make it more appropriate for
      obtaining accurate values of primary implant stability than solid-bone blocks.
      For the cellular-rigid bone models, the ISQ increased with the elastic modulus of
      cancellous bone. The regression correlation coefficient was 0.96 for correlations
      of the ISQ with the elasticity of cancellous bone and with the 3D BIC%. The
      initial implant stability was moderately positively correlated with the
      elasticity of cancellous bone and with the 3D BIC%.

PMID- 22867740
TI  - Investigation of an autologous blood treatment strategy for temporomandibular
      joint hypermobility in a pig model.
AB  - Many different surgical and non-surgical techniques are used for the treatment of
      temporomandibular joint (TMJ) hypermobility. One of these methods is autologous
      blood injection into the TMJ. The fate of the autologous blood used for treatment
      of recurring condylar dislocation is still not completely understood. The authors
      used 12 pigs (Sus scrota f. domestica) as a model species for autologous blood
      delivery into the TMJ. Blood injection was followed by histopathological analysis
      at different times after treatment (1h, 1, 2 and 4 weeks). Samples were examined
      by magnetic resonance imaging, macroscopic and histological methods. The
      deposition of the remaining blood was observed in the form of clots in the distal
      parts of the upper joint cavity 1h and 1 week after treatment. 2 weeks after
      treatment, small blood clots were still apparent in the distal part of the upper
      joint cavity. 4 weeks after surgery, no remnants of blood, changes or adhesions
      were apparent inside the TMJ. No morphological or histological changes were
      observed in the TMJ after the injection of autologous blood suggesting another
      mechanism is involved in the hypermobility treatment.

PMID- 22867741
TI  - Asbestos exposure from the overhaul of a Pratt & Whitney R2800 engine.
AB  - This study assessed the asbestos exposures of airplane piston engine mechanics
      while performing overhaul work on a Pratt & Whitney R2800 radial engine, with
      tools and practices in use since the time these engines were manufactured.
      Approximately 40% of the bulk samples collected during this test were found to
      contain chrysotile. Air samples were collected during the overhaul and were
      analyzed by phase contrast microscopy (PCM) and transmission electron microscopy
      (TEM). The average worker exposure during disassembly was 0.0272f/ml (PCM) and
      ranged from 0.0013 to 0.1240f/ml (PCM) during an average sample collection time
      of 188min. The average worker exposure during reassembly was 0.0198f/ml (PCM) and
      ranged from 0.0055 to 0.0913f/ml (PCM) during an average sample collection time
      of 222min. Only one worker sample (during reassembly) was found to contain
      asbestos at a concentration of 0.0012f/ml (PCME). Similar results should be found
      in other aircraft piston engines that use metal clad and non-friable asbestos
      gaskets, which are the current standard in aircraft piston engines.

PMID- 22867742
TI  - A stepwise protocol to coat aAPC beads prevents out-competition of anti-CD3 mAb
      and consequent experimental artefacts.
AB  - Artificial antigen-presenting cells (aAPC) are widely used for both clinical and
      basic research applications, as cell-based or bead-based scaffolds, combining
      immune synapse components of interest. Adequate and controlled preparation of
      aAPCs is crucial for subsequent immunoassays. We reveal that certain proteins
      such as activatory anti-CD3 antibody can be out-competed by other proteins (e.g.
      inhibitory receptor ligands such as PDL1:Fc) during the coating of aAPC beads,
      under the usually performed coating procedures. This may be misleading, as we
      found that decreased CD8 T cell activity was not due to inhibitory receptor
      triggering but rather because of unexpectedly low anti-CD3 antibody density on
      the beads upon co-incubation with inhibitory receptor ligands. We propose an
      optimized protocol, and emphasize the need to quality-control the coating of
      proteins on aAPC beads prior to their use in immunoassays.

PMID- 22867743
TI  - Prevention of false positive binding during immunofluorescence of Staphylococcus
      aureus infected tissue biopsies.
AB  - Immunofluorescence is a fundamental tool used to analyse tissue and cell samples
      with a wide variety of available antibodies targeting specific proteins or
      molecules. Staphylococcal surface protein A is used both in clinical, research
      and industrial settings for its ability to bind mammalian immunoglobulin G.
      Spurious binding between protein A and IgG antibodies can lead to false-positive
      fluorescence and misleading results. Here we demonstrate this occurring in
      formalin-fixed patient samples that harbour Staphylococcus aureus infection, and
      characterise methods to overcome this issue. Specifically the use of F(ab')
      fragment antibodies or blocking with human IgG is shown to prevent antibody
      protein A interaction in formalin-fixed S. aureus smears, biopsies obtained from
      infected patients, and experimentally infected tissue samples.

PMID- 22867745
TI  - Comparison of manual and automated DNA purification for measuring TREC in dried
      blood spot (DBS) samples with qPCR.
AB  - Automated nucleic acid extractions from dried blood spot (DBS) samples promises
      standardized sample treatment, low error rates, avoidance of contamination and
      requirement of less hands-on time. In the present study, non-automated and
      automated column based extraction processes using the QIAamp Investigator
      procedure were compared for the extraction of DNA from DBS samples. The
      concentration and the purity of DNA generated were determined by optical density
      readings. Furthermore qPCR downstream applications using the nucleic acids
      extracted with the two processes and albumin and T-cell receptor excision circles
      (TREC) copy numbers were measured and compared. The influence of the time of
      storage was also investigated by analyzing samples freshly dried and stored up to
      11weeks at -20 degrees C from the same individual. Finally, we provide arguments
      of preferentially choosing the automated procedure for extracting DNAs from DBS
      samples when downstream qPCR applications are required.

PMID- 22867744
TI  - Isolation and characterization of pharmaceutical grade human pentraxins, serum
      amyloid P component and C-reactive protein, for clinical use.
AB  - The human pentraxin proteins, serum amyloid P component (SAP) and C-reactive
      protein (CRP) are important in routine clinical diagnosis, SAP for systemic
      amyloidosis and CRP for monitoring the non-specific acute phase response. They
      are also targets for novel therapies currently in development but their roles in
      health and disease are controversial. Thus, both for clinical use and to
      rigorously elucidate their functions, structurally and functionally intact,
      pharmaceutical grade preparations of the natural, authentic proteins are
      required. We report here the production from normal human donor plasma and the
      characterization of the first such preparations. Importantly, we demonstrate
      that, contrary to reports using recombinant proteins and less well characterized
      preparations, neither CRP nor SAP stimulate the release by human peripheral blood
      mononuclear cells in vitro of any TNFalpha, IL-6 or IL-8, nor does SAP cause
      release of IL-1beta or IL-10. Furthermore neither of our preparations was pro
      inflammatory in mice in vivo.

PMID- 22867746
TI  - Retroviral transduction of lineage antigen-negative ((Lin-) cells: a valuable
      alternative for the generation of T cell receptor (TCR) retrogenic mice.
AB  - Mice with virtually all T cells expressing a single T cell receptor (TCR) on
      their surface have been instrumental in understanding the development of immature
      thymocytes. For many years, such an engineering has been achieved essentially by
      inserting rearranged TCR alpha and beta chain coding sequences into the genome
      through co-microinjection into fertilized eggs (TCR transgenesis). More recently,
      a novel methodology relying on the reconstitution of T cell deficient hosts with
      retrovirally-transduced multipotent bone marrow cells has been developed. Hence,
      TCR retrogenesis allows for the in vivo study of given TCR specificities in a
      faster and less expensive manner. While initial procedures were taking advantage
      of 5-Fluorouracil (5-FU) treatment of RAG-deficient or SCID donor mice as source
      of haematopoietic stem cells, we used bone marrow cell suspensions enriched in
      lineage antigen-negative (Lin-) cells from untreated donors for TCR retrogenesis.
      In contrast to cells from 5-FU-treated donors, transduced Lin-cells consistently
      generated a sizable retrogenic pool of thymocytes and required less donor mice.
      In such retrogenic mice, immature thymocytes bearing a major histocompatibility
      complex (MHC) class II-restricted TCR differentiated into the expected CD4 mature
      T cell lineage and populated the peripheral lymphoid organs where they retained
      the capacity to react to their cognate ligand. Lin- cell-enriched BM cells
      represent therefore, a reliable alternative to 5-FU treatment for retroviral
      transduction of haematopoietic stem cells and TCR retrogenic derivation.

PMID- 22867747
TI  - Radon monitoring in sites of economical importance in Jamaica.
AB  - The main task was to evaluate possible radon risk to the public and workers in
      four caves of economical importance. Green Grotto Cave is a large labyrinthine
      limestone cave, open to the tourism; kept Rn concentration in the range 30-40 Bq
      m(-3). Xtabil a coral limestone sea cave is part of a beach resort resulted in
      very low radon concentration of 10 Bq m(-3). Windsor is an intricate limestone
      cave system showed Rn concentration in the range 250-350 Bq m(-3). Whereas the
      Oxford caves, is situated in a region of high radioactivity in soil due to the
      bauxite mines, reached a maximum of 2592 Bq m(-3).

PMID- 22867748
TI  - Side branch ligation for haemodialysis-access-induced distal ischaemia.
AB  - OBJECTIVE: Chronic hand ischaemia is occasionally observed in haemodialysis
      patients with a brachiocephalic fistula using the Gracz technique. Open venous
      side branches of the access may contribute to lower peripheral perfusion
      pressures. This study reports on the effects of access side branch ligation (SBL)
      on ischaemia in patients with haemodialysis access induced distal ischaemia
      (HAIDI). DESIGN, MATERIALS AND METHODS: Hand ischaemia was quantified using a
      published questionnaire (HIQ, minimal 0 points: no ischaemia, maximal 500:
      excruciating ischaemia). Finger pressures (P(dig), mmHg), digital brachial index
      (DBI) and access flow were measured before and after SBL. RESULTS: Twenty-two
      patients were operated for grade 2-4 HAIDI during 7 years, and 12 underwent SBL
      (as single procedure n = 5, preceeding banding/DRIL n = 7). Hand ischaemia was
      attenuated after SBL only (n = 5, HIQ 216 +/- 39 vs. 73 +/- 26, P = 0.04). A 25%
      increase was observed in both P(dig) (n = 12, before SBL: 57 +/- 8 mmHg, after:
      72 +/- 8 mmHg, P = 0.012) and DBI (before SBL: 0.49 +/- 0.06, after: 0.61 +/-
      0.04, P = 0.006). Access flow did not change. All patients successfully resumed
      dialysis. CONCLUSION: SBL may be effective as single or adjunctive surgical
      procedure in the treatment of HAIDI in the presence of a Gracz fistula.

PMID- 22867749
TI  - The anabolic potential of dietary protein intake on skeletal muscle is prolonged
      by prior light-load exercise.
AB  - BACKGROUND & AIMS: Hyperaminoacidemia stimulates myofibrillar fractional
      synthesis rate (myoFSR) transiently in resting skeletal muscle. We investigated
      whether light-load resistance exercise can extent this responsiveness. METHODS:
      Ten healthy males exercised one leg with a light-load resistance-like exercise at
      16% of 1 repetition maximum and received oral protein boluses every hour for a 10
      h period. Their myoFSR was determined by [1-(13)C]-leucine incorporation. Muscle
      biopsies were obtained from the resting (REST) and exercised (EXC) muscles every
      2.5-h in the protein-fed period. RESULTS: Protein feeding significantly elevated
      plasma leucine and essential amino acids by an average of 39 +/- 9% (mean +/-
      SEM) and 20 +/- 4%, respectively, compared to the basal concentrations: 197 +/-
      12 MUmol L(-1) and 854 +/- 35 MUmol L(-1), respectively. The myoFSR was similar
      in EXC and REST muscles in the first 8 h (all time intervals p > 0.05). After 8 h
      the myoFSR dropped in the REST muscle to 0.041 +/- 0.005%.h(-1), which was 65 +/-
      5% of the rate in EXC leg at the same time point (0.062 +/- 0.004%.h(-1)) and 80
      +/- 14% of the level in REST leg from 0.5 to 8 h (0.056 +/- 0.005%.h(-1))
      (interaction p < 0.05). CONCLUSIONS: Compared to rest, light-load exercise
      prolonged the stimulatory effect of dietary protein on muscle biosynthesis
      providing perspectives for a muscle restorative effect in clinical settings where
      strenuous activity is intolerable.

PMID- 22867750
TI  - Severe hypoglycemia with "Big"-IGF-2 oversecretion by a giant phyllode tumor of
      the breast: a rare case of non-islet cell tumor-induced hypoglycemia (NICTH).
AB  - OBJECTIVE: We report an exceptional case of non-islet cell tumor-induced
      hypoglycemia (NICTH) secondary to "Big"-IGF-2 oversecretion due to a giant
      phyllode tumor of the breast. CLINICAL PRESENTATION: A 49-year-old woman was
      admitted in emergency for brutal neurologic defect revealing severe hypoglycemia.
      Several similar episodes were observed throughout hospitalization, requiring
      continue perfusion of hypertonic glucose solution. Beside these metabolic
      disorders, we observed a giant and hard tumor of the left breast (about 30cm in
      diameter). INTERPRETATION: Supplementary blood analysis revealed serum levels of
      C-peptide and insulin suppressed during hypoglycemia, excluding the possibility
      of either endogenous or exogenous hyperinsulinism. Low plasma levels of GH and
      IGF-1 were found, suggesting a negative feedback loop on somatotroph axis
      function. Therefore, the hypothesis of an insulinomimetic compound released by
      tumor cells was evoked because of abnormal presence of high-weight and immature
      form of IGF-2 (called "Big"-IGF-2) in the serum identified by western immunoblot
      analysis. A left mastectomy was performed and completely restored glucose
      homeostasis and confirmed the paraneoplastic origin of hypoglycemia because of
      markedly elevated expression of IGF-2 mRNA (qPCR) within the tumor cells.
      Finally, the anatomopathology analysis diagnosed a mesenchymatous tumor, namely a
      high-grade phyllode sarcoma of the breast. CONCLUSION: Although NICTH due to
      "Big"-IGF-2 overproduction is a rare phenomenon, mainly observed in case of
      mesenchymatous tumor, it should be considered in presence of severe hypoglycemia
      with voluminous tumor and without hyperinsulinism.

PMID- 22867751
TI  - Contrast of hemispheric lateralization for oro-facial movements between learned
      attention-getting sounds and species-typical vocalizations in chimpanzees:
      extension in a second colony.
AB  - Studies involving oro-facial asymmetries in nonhuman primates have largely
      demonstrated a right hemispheric dominance for communicative signals and
      conveyance of emotional information. A recent study on chimpanzee reported the
      first evidence of significant left-hemispheric dominance when using attention
      getting sounds and rightward bias for species-typical vocalizations (Losin,
      Russell, Freeman, Meguerditchian, Hopkins & Fitch, 2008). The current study
      sought to extend the findings from Losin et al. (2008) with additional oro-facial
      assessment in a new colony of chimpanzees. When combining the two populations,
      the results indicated a consistent leftward bias for attention-getting sounds and
      a right lateralization for species-typical vocalizations. Collectively, the
      results suggest that both voluntary-controlled oro-facial and gestural
      communication might share the same left-hemispheric specialization and might have
      coevolved into a single integrated system present in a common hominid ancestor.

PMID- 22867752
TI  - The phonotactic influence on the perception of a consonant cluster /pt/ by native
      English and native Polish listeners: a behavioral and event related potential
      (ERP) study.
AB  - The effect of exposure to the contextual features of the /pt/ cluster was
      investigated in native-English and native-Polish listeners using behavioral and
      event-related potential (ERP) methodology. Both groups experience the /pt/
      cluster in their languages, but only the Polish group experiences the cluster in
      the context of word onset examined in the current experiment. The /st/ cluster
      was used as an experimental control. ERPs were recorded while participants
      identified the number of syllables in the second word of nonsense word pairs. The
      results found that only Polish listeners accurately perceived the /pt/ cluster
      and perception was reflected within a late positive component of the ERP
      waveform. Furthermore, evidence of discrimination of /pt/ and /pet/ onsets in the
      neural signal was found even for non-native listeners who could not perceive the
      difference. These findings suggest that exposure to phoneme sequences in highly
      specific contexts may be necessary for accurate perception.

PMID- 22867753
TI  - Postprandial hypertension, an overlooked risk marker for arteriosclerosis.
AB  - OBJECTIVE: Increased blood pressure (BP) variability is suggested to be a risk
      factor for cardiovascular disease. Although a postprandial decline in BP is a
      frequently observed phenomenon in the elderly, little attention has been paid to
      the clinical and diagnostic significance of postprandial BP change. Here, we
      aimed to clarify the possible association between postprandial BP dysregulation
      and arteriosclerosis. METHODS: The study subjects were 1339 apparently healthy
      middle-aged to elderly persons (66 +/- 9 years old). Postprandial changes in BP
      were calculated by two readings on the same day, one just before lunch with a
      standardized Japanese meal and the second 30 min after lunch. Arteriosclerosis
      was assessed by carotid intima-media thickness and brachial-to-ankle pulse wave
      velocity. RESULTS: Mean preprandial and postprandial systolic BP was 127 +/- 18
      and 123 +/- 18 mmHg respectively. One hundred and twelve subjects (8.4%) showed a
      greater than 20-mmHg postprandial decline in systolic BP, while 129 (9.6%) showed
      a greater than 10-mmHg increase. Arteriosclerosis was significantly higher in
      both postprandial hypotensive and hypertensive subjects. The postprandial changes
      in systolic BP were strongly associated with preprandial systolic BP (r = 0.335,
      p < 0.001). The association between postprandial hypotension and increased
      arteriosclerosis was therefore lost after adjustment for basal systolic BP.
      Multiple linear regression analysis adjusted for possible covariates, including
      basal BP, identified a postprandial increase in BP as an independent determinant
      of insulin resistance as assessed by HOMA-IR (beta = 0.093, p < 0.001), carotid
      thickness (beta = 0.086, p = 0.001) and pulse wave velocity (beta = 0.170, p <
      0.001). CONCLUSION: Postprandial increase in BP is a novel risk marker for
      arteriosclerosis.

PMID- 22867754
TI  - Bone defects in LPA receptor genetically modified mice.
AB  - LPA and LPA(1) have been shown to increase osteoblastic proliferation and
      differentiation as well as activation of osteoclasts. Cell and animal model
      studies have suggested that LPA is produced by bone cells and bone tissues. We
      obtained data from invalidated mice which support the hypothesis that LPA(1) is
      involved in bone development by promoting osteogenesis. LPA(1)-invalidated mice
      demonstrate growth and sternal and costal abnormalities, which highlights the
      specific roles of LPA(1) during bone development. Microcomputed tomography and
      histological analysis demonstrate osteoporosis in the trabecular and cortical
      bone of LPA(1)-invalidated mice. Moreover, bone marrow mesenchymal progenitors
      from these mice displayed decreased osteoblastic differentiation. Infrared
      analysis did not indicate osteomalacia in the bone tissue of LPA(1)-invalidated
      mice. LPA(1) displays opposite effects to LPA(4) on the related G proteins G(i)
      and G(s), responsible for decrease and increase of the cAMP level respectively,
      which itself is essential to the control of osteoblastic differentiation. The
      opposite effects of LPA(1) and LPA(4) during osteoblastic differentiation support
      the possibility that new pharmacological agents derived from the LPA pathways
      could be found and used in clinical practice to positively influence bone
      formation and treat osteoporosis. The paracrine effect of LPA is potentially
      modulated by its concentration in bone tissues, which may result from various
      intracellular and extracellular pathways. The relevance of LPA(1) in bone
      remodeling, as a receptor able to influence both osteoblast and osteoclast
      activity, still deserves further clarification. This article is part of a Special
      Issue entitled Advances in Lysophospholipid Research.

PMID- 22867755
TI  - Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and
      ATX/LPA axes.
AB  - Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent
      lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids,
      joining thromboxanes, leukotrienes and prostaglandins with which they share
      metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and
      LPA metabolism, such as the phospholipase A(2) superfamily (PLA(2)) and autotaxin
      (ATX, ENPP2), play central roles in regulating LPC and LPA levels and
      consequently their actions. LPC/LPA biosynthetic pathways will be briefly
      presented and LPC/LPA signaling properties and their possible functions in the
      regulation of the immune system and chronic inflammation will be reviewed.
      Furthermore, implications of exacerbated LPC and/or LPA signaling in the context
      of chronic inflammatory diseases, namely rheumatoid arthritis, multiple
      sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is
      part of a Special Issue entitled Advances in Lysophospholipid Research.

PMID- 22867756
TI  - Assessment of possible allergenicity of hypothetical ORFs in common food crops
      using current bioinformatic guidelines and its implications for the safety
      assessment of GM crops.
AB  - Before a genetically modified (GM) crop can be commercialized it must pass
      through a rigorous regulatory process to verify that it is safe for human and
      animal consumption, and to the environment. One particular area of focus is the
      potential introduction of a known or cross-reactive allergen not previously
      present within the crop. The assessment of possible allergenicity uses the
      guidelines outlined by the Food and Agriculture Organization (FAO) and World
      Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all
      newly expressed proteins. Some regulatory authorities have broadened the scope of
      the assessment to include all DNA reading frames between stop codons across the
      insert and spanning the insert/genomic DNA junctions. To investigate the utility
      of this bioinformatic assessment, all naturally occurring stop-to-stop frames in
      the non-transgenic genomes of maize, rice, and soybean, as well as the human
      genome, were compared against the AllergenOnline (www.allergenonline.org)
      database using the Codex criteria. We discovered thousands of frames that
      exceeded the Codex defined threshold for potential cross-reactivity suggesting
      that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value
      for making decisions on the safety of GM crops.

PMID- 22867758
TI  - Bilateral tonsilloliths and calcified carotid atheromas: case report and
      literature review.
AB  - Tonsilloliths and calcified carotid atheromas are dystrophic calcifications that
      can be identified in routine oral radiographs. This case report is the first
      description in the English literature of the simultaneous occurrence of bilateral
      tonsilloliths and calcified carotid atheromas. Panoramic oral radiographs from a
      62-year-old woman presented bilateral radiopaque images of the left and right
      ramus of the mandible; multiple and well-defined radiopacities below the left
      angle of the mandible, next to the C3-C4 cervical vertebrae; and a single
      radiopacity on the right side between the hyoid bone and the mandible base.
      Computed tomography confirmed the exact location of the calcifications in the
      oropharyngeal and carotid spaces. A diagnosis of bilateral tonsilloliths and
      calcified carotid atheromas was reached. Doppler ultrasound indicated a degree of
      stenosis of +/- 20% within the right and left carotids. The patient was referred
      to a vascular surgeon to evaluate the calcified carotid atheromas. Follow-up of
      the tonsilloliths was also performed.

PMID- 22867759
TI  - Adult zebrafish model of bacterial meningitis in Streptococcus agalactiae
      infection.
AB  - Streptococcus agalactiae (Group B Streptococcus, GBS) is the major cause of
      severe bacterial disease and meningitis in newborns. The zebrafish (Danio rerio)
      has recently emerged as a valuable and powerful vertebrate model for the study of
      human streptococcal infections. In the present study we demonstrate that adult
      zebrafish are susceptible to GBS infection through the intraperitoneal and
      intramuscular routes of infection. Following intraperitoneal challenge with GBS,
      zebrafish developed a fulminant infection 24-48 h post-injection, with signs of
      pathogenesis including severe inflammation at the injection site and
      meningoencephalitis. Quantification of blood and brain bacterial load confirmed
      that GBS is capable of replicating in the zebrafish bloodstream and penetrating
      the blood-brain barrier, resulting in the induction of host inflammatory immune
      responses in the brain. Additionally, we show that GBS mutants previously
      described as avirulent in the mice model, have an impaired ability to cause
      meningitis in this new in vivo model. Taken together, our data demonstrates that
      adult zebrafish may be used as a bacterial meningitis model as a means for
      deciphering the pathogenesis and development of invasive GBS disease.

PMID- 22867760
TI  - Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims
      with post traumatic stress disorder.
AB  - BACKGROUND: In chronic sexual abuse victims with post traumatic stress disorder
      (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In
      single rape victims, PTSD symptoms are hypothesized to function as a chronic
      stressor leading to similar HPA-axis dysregulation. The objective of the current
      study was to assess HPA-axis functioning in female adolescents with rape-related
      PTSD, but no prior sexual trauma, in comparison to non-victimized controls.
      METHOD: Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were
      measured in 52 female adolescent rape victims with PTSD and 37 healthy
      adolescents at 0, 15, 30, 45 and 60 min after awakening, both under basal
      conditions and after 0.5 mg dexamethasone administration. RESULTS: Compared to
      age-matched controls, adolescent rape victims with PTSD showed significantly
      reduced cortisol and DHEAS levels. No group differences for the effect of
      dexamethasone suppression were found. Both the event of rape and PTSD diagnosis,
      and not factors such as sleep duration, smoking, education or oral
      contraceptives, accounted for the neuroendocrine differences between rape victims
      and controls. CONCLUSIONS: The results show evidence for a dysregulated HPA-axis
      in female adolescent victims of single sexual trauma with PTSD. The finding of
      hypocortisolism is consistent with endocrine dysfunctioning in chronic sexual
      abuse victims and may have clinical implications with regard to treatment
      possibilities.

PMID- 22867761
TI  - Tribological altruism: A sacrificial layer mechanism of synovial joint
      lubrication in articular cartilage.
AB  - Boundary lubrication is characterized by sliding surfaces separated by a
      molecularly thin film that reduces friction and wear of the underlying substrate
      when fluid lubrication cannot be established. In this study, the wear and
      replenishment rates of articular cartilage were examined in the context of
      friction coefficient changes, protein loss, and direct imaging of the surface
      ultrastructure, to determine the efficiency of the boundary lubricant (BL) layer.
      Depletion of cartilage lubricity occurred with the concomitant loss of surface
      proteoglycans. Restoration of lubrication by incubation with synovial fluid was
      much faster than incubation with culture media and isolated superficial zone
      protein. The replenishment action of the BL layer in articular cartilage was
      rapid, with the rate of formation exceeding the rate of depletion of the BL layer
      to effectively protect the tissue from mechanical wear. The obtained results
      indicate that boundary lubrication in articular cartilage depends in part on a
      sacrificial layer mechanism. The present study provides insight into the natural
      mechanisms that minimize wear and resist tissue degeneration over the lifetime of
      an organism.

PMID- 22867762
TI  - Sensitivity of subject-specific models to errors in musculo-skeletal geometry.
AB  - Subject-specific musculo-skeletal models of the lower extremity are an important
      tool for investigating various biomechanical problems, for instance the results
      of surgery such as joint replacements and tendon transfers. The aim of this study
      was to assess the potential effects of errors in musculo-skeletal geometry on
      subject-specific model results. We performed an extensive sensitivity analysis to
      quantify the effect of the perturbation of origin, insertion and via points of
      each of the 56 musculo-tendon parts contained in the model. We used two metrics,
      namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to
      distinguish the effect of the perturbation on the predicted force produced by
      only the perturbed musculo-tendon parts and by all the remaining musculo-tendon
      parts, respectively, during a simulated gait cycle. Results indicated that, for
      each musculo-tendon part, only two points show a significant sensitivity: its
      origin, or pseudo-origin, point and its insertion, or pseudo-insertion, point.
      The most sensitive points belong to those musculo-tendon parts that act as prime
      movers in the walking movement (insertion point of the Achilles Tendon:
      LSI=15.56%, OSI=7.17%; origin points of the Rectus Femoris: LSI=13.89%,
      OSI=2.44%) and as hip stabilizers (insertion points of the Gluteus Medius
      Anterior: LSI=17.92%, OSI=2.79%; insertion point of the Gluteus Minimus:
      LSI=21.71%, OSI=2.41%). The proposed priority list provides quantitative
      information to improve the predictive accuracy of subject-specific musculo
      skeletal models.

PMID- 22867763
TI  - Medial gastrocnemius muscle fascicle active torque-length and Achilles tendon
      properties in young adults with spastic cerebral palsy.
AB  - Individuals with spastic cerebral palsy (CP) typically experience muscle
      weakness. The mechanisms responsible for muscle weakness in spastic CP are
      complex and may be influenced by the intrinsic mechanical properties of the
      muscle and tendon. The purpose of this study was to investigate the medial
      gastrocnemius (MG) muscle fascicle active torque-length and Achilles tendon
      properties in young adults with spastic CP. Nine relatively high functioning
      young adults with spastic CP (GMFCS I, 17+/-2 years) and 10 typically developing
      individuals (18+/-2 years) participated in the study. Active MG torque-length and
      Achilles tendon properties were assessed under controlled conditions on a
      dynamometer. EMG was recorded from leg muscles and ultrasound was used to measure
      MG fascicle length and Achilles tendon length during maximal isometric
      contractions at five ankle angles throughout the available range of motion and
      during passive rotations imposed by the dynamometer. Compared to the typically
      developing group, the spastic CP group had 33% lower active ankle plantarflexion
      torque across the available range of ankle joint motion, partially explained by
      37% smaller MG muscle and 4% greater antagonistic co-contraction. The Achilles
      tendon slack length was also 10% longer in the spastic CP group. This study
      confirms young adults with mild spastic CP have altered muscle-tendon mechanical
      properties. The adaptation of a longer Achilles tendon may facilitate a greater
      storage and recovery of elastic energy and partially compensate for decreased
      force and work production by the small muscles of the triceps surae during
      activities such as locomotion.

PMID- 22867764
TI  - Analysis of microstructural and mechanical alterations of trabecular bone in a
      simulated three-dimensional remodeling process.
AB  - Bone remodeling is a complex dynamic process, which modulates both bone mass and
      bone microstructure. In addition to bone mass, bone microstructure is an
      important contributor to bone quality in osteoporosis and fragility fractures.
      However, the quantitative knowledge of evolution of three-dimensional (3D)
      trabecular microstructure in adaptation to the external forces is currently
      limited. In this study, a new 3D simulation method of remodeling of human
      trabecular bone was developed to quantitatively study the dynamic evolution of
      bone mass and trabecular microstructure in response to different external loading
      conditions. The morphological features of trabecular plate and rod, such as
      thickness and number density in different orientations were monitored during the
      remodeling process using a novel imaging analysis technique, namely Individual
      Trabecula Segmentation (ITS). We showed that the volume fraction and
      microstructures of trabecular bone including, trabecular type and orientation,
      were determined by the applied mechanical load. Particularly, the morphological
      parameters of trabecular plates were more sensitive to the applied load,
      indicating that they played the major role in the mechanical properties of the
      trabecular bone. Reducing the applied load caused severe microstructural
      deteriorations of trabecular bone, such as trabecular plate perforation, rod
      breakage, and a conversion from plates to rods.

PMID- 22867765
TI  - Influence of a freeze-thaw cycle on the stress-stretch curves of tissues of
      porcine abdominal organs.
AB  - The paper investigates both fresh porcine spleen and liver and the possible
      decomposition of these organs under a freeze-thaw cycle. The effect of tissue
      preservation condition is an important factor which should be taken into account
      for protracted biomechanical tests. In this work, tension tests were conducted
      for a large number of tissue specimens from twenty pigs divided into two groups
      of 10. Concretely, the first group was tested in fresh state; the other one was
      tested after a freeze-thaw cycle which simulates the conservation conditions
      before biomechanical experiments. A modified Fung model for isotropic behavior
      was adopted for the curve fitting of each kind of tissues. Experimental results
      show strong effects of the realistic freeze-thaw cycle on the capsule of elastin
      rich spleen but negligible effects on the liver which virtually contains no
      elastin. This different behavior could be explained by the autolysis of elastin
      by elastolytic enzymes during the warmer period after thawing. Realistic
      biomechanical properties of elastin-rich organs can only be expected if really
      fresh tissue is tested. The observations are supported by tests of intestines.

PMID- 22867766
TI  - Evaluation of gait and slip parameters for adults with intellectual disability.
AB  - Adults with intellectual disability (ID) experience more falls than their non
      disabled peers. A gait analysis was conducted to quantify normal walking, and an
      additional slip trial was performed to measure slip response characteristics for
      adults with ID as well as a group of age- and gender-matched controls. Variables
      relating to gait pattern, slip propensity, and slip severity were assessed to
      compare the differences between groups. The ID group was found to have
      significantly slower walking speed, shorter step lengths, and increased knee
      flexion angles at heel contact. These gait characteristics are known to reduce
      the likelihood of slip initiation in adults without ID. Despite a more cautious
      gait pattern, however, the ID group exhibited greater slip distances indicating
      greater slip severity. This study suggests that falls in this population may be
      due to deficient slip detection or insufficient recovery response.

PMID- 22867767
TI  - Heterogeneous effects of health insurance on out-of-pocket expenditure on
      medicines in Mexico.
AB  - OBJECTIVE: Given the importance of health insurance for financing medicines and
      recent policy changes designed to reduce health-related out-of-pocket expenditure
      (OOPE) in Mexico, our study examined and analyzed the effect of health insurance
      on the probability and amount of OOPE for medicines and the proportion spent from
      household available expenditure (AE) funds. METHODS: We conducted a cross
      sectional analysis by using the Mexican National Household Survey of Income and
      Expenditures for 2008. Households were grouped according to household medical
      insurance type (Social Security, Seguro Popular, mixed, or no affiliation). OOPE
      for medicines and health costs, and the probability of occurrence, were estimated
      with linear regression models; subsequently, the proportion of health
      expenditures from AE was calculated. The Heckman selection procedure was used to
      correct for self-selection of health expenditure; a propensity score matching
      procedure and an alternative procedure using instrumental variables were used to
      correct for heterogeneity between households with and without Seguro Popular.
      RESULTS: OOPE in medicines account for 66% of the total health expenditures and
      5% of the AE. Households with health insurance had a lower probability of OOPE
      for medicines than their comparison groups. There was heterogeneity in the health
      insurance effect on the proportion of OOPE for medicines out of the AE, with a
      reduction of 1.7% for households with Social Security, 1.4% for mixed
      affiliation, but no difference between Seguro Popular and matched households
      without insurance. CONCLUSION: Medicines were the most prevalent component of
      health expenditures in Mexico. We recommend improving access to health services
      and strengthening access to medicines to reduce high OOPE.

PMID- 22867768
TI  - The clinical and economic burden of poor adherence and persistence with
      osteoporosis medications in Ireland.
AB  - OBJECTIVES: Medication nonadherence is common for osteoporosis, but its
      consequences have not been well described. This study aimed to quantify the
      clinical and economic impacts of poor adherence and to evaluate the potential
      cost-effectiveness of improving patient adherence by using hypothetical
      behavioral interventions. METHODS: A previously validated Markov microsimulation
      model was adapted to the Irish setting to estimate lifetime costs and outcomes
      (fractures and quality-adjusted life-year [QALY]) for three adherence scenarios:
      no treatment, real-world adherence, and full adherence over 3 years. The real
      world scenario employed adherence and persistence data from the Irish Health
      Services Executive-Primary Care Reimbursement Services pharmacy claims database.
      We also investigated the cost-effectiveness of hypothetical behavioral
      interventions to improve medication adherence (according to their cost and effect
      on adherence). RESULTS: The number of fractures prevented and the QALY gain
      obtained at real-world adherence levels represented only 57% and 56% of those
      expected with full adherence, respectively. The costs per QALY gained of real
      world adherence and of full adherence compared with no treatment were estimated
      at ? 11,834 and ? 6,341, respectively. An intervention to improve adherence by
      25% would result in an incremental cost-effectiveness ratio of ? 11,511 per QALY
      and ? 54,182 per QALY, compared with real-world adherence, if the intervention
      cost an additional ? 50 and ? 100 per year, respectively. DISCUSSION: Poor
      adherence with osteoporosis medications results in around a 50% reduction in the
      potential benefits observed in clinical trials and a doubling of the cost per
      QALY gained from these medications. Depending on their costs and outcomes,
      programs to improve adherence have the potential to be an efficient use of
      resources.

PMID- 22867769
TI  - Cost-effectiveness of expanded newborn screening in Texas.
AB  - OBJECTIVE: Texas House Bill 790 resulted in the expansion of the newborn
      screening panel from 7 disorders to 27 disorders. Implementation of this change
      began in 2007. The objective of this study was to estimate the incremental cost
      effectiveness of the expanded newborn screening program compared with the
      previous standard screening in Texas. METHODS: A Markov model (for a hypothetical
      cohort of Texas births in 2007) was constructed to compare lifetime costs and
      quality-adjusted life-years (QALYs) between the expanded newborn screening and
      preexpansion newborn screening. Estimates of costs, probabilities of sequelae,
      and utilities for disorder categories were obtained from a combination of Texas
      statistics, the literature, and expert opinion. A baseline discount rate of 3%
      was used for both costs and QALYs, with a range of 0% to 5%. Analyses were
      conducted from a payer's perspective, and so only direct medical cost estimates
      were included. RESULTS: The lifetime incremental cost-effectiveness ratio for
      expanded versus preexpansion screening was about $11,560 per QALY. The results
      remained robust to both deterministic and probabilistic sensitivity analyses.
      CONCLUSIONS: Expanded newborn screening does result in additional expenses to the
      payer, but it also improves patient outcomes by preventing avoidable morbidity
      and mortality. The screened population benefits from greater QALYs as compared
      with the unscreened population. Overall, expanded newborn screening in Texas was
      estimated to be a cost-effective option as compared with unexpanded newborn
      screening.

PMID- 22867770
TI  - Cost-effectiveness analysis of the bivalent compared with the quadrivalent human
      papillomavirus vaccines in Taiwan.
AB  - OBJECTIVE: To compare the epidemiological and economic impact of additional cross
      protection against oncogenic human papillomavirus (HPV) types beyond 16/18 of the
      bivalent vaccine (BV) versus protection against nononcogenic HPV types 6/11 of
      the quadrivalent vaccine (QV) in Taiwan. METHODS: A lifetime Markov model
      calibrated to the Taiwanese setting simulated the natural history of low-risk
      (engendering cervical intraepithelial neoplasia [CIN] 1 and genital warts) and
      high-risk HPV (engendering CIN1, CIN2/3, and cervical cancer [CC]) infections,
      screening, and vaccination (100% coverage) for a cohort of 12-year-old girls (N =
      153,000). Transition probabilities, costs, and utilities were estimated from
      published data and expert opinion. Vaccine efficacy was obtained from each
      vaccine's respective clinical trials. Price-parity and lifelong protection was
      assumed for both vaccines. The number of CIN lesions, CC cases, CC deaths and
      genital wart (GW) cases, and quality-adjusted life-years were estimated. Costs
      and outcomes (discounted at 3% and 1.5%, respectively) were compared from a
      payer's perspective. RESULTS: The model estimated that the BV led to an
      additional, undiscounted, 11,484 CIN1, 1,779 (+34.3% vs. QV) CIN2/3, 188 (+29.0%
      vs. QV) CC, and 69 (+29.0% vs. QV) CC deaths prevented compared with the QV,
      while the QV prevented 4,150 GW (+71%). This resulted in an additional 768
      quality-adjusted life-years (QALY) and 11.6 million new Taiwan dollars costs
      saved for the BV versus the QV after discounting. CONCLUSION: Both vaccines have
      a different epidemiological impact with an increased number of CC-related lesions
      potentially prevented for the BV because of additional cross-protection. In the
      Taiwanese setting, HPV mass vaccination using the BV was estimated to dominate
      vaccination using the QV.

PMID- 22867771
TI  - Cost-effectiveness of sensor-augmented pump therapy in adults with type 1
      diabetes in the United States.
AB  - OBJECTIVES: A recent randomized trial demonstrated significant reductions in
      hemoglobin A(1c) levels with sensor-augmented pump therapy (SAPT) compared with
      multiple daily injections of insulin (MDI) in type 1 diabetes. We analyzed
      resource use in the trial and estimated the long-term cost-effectiveness of SAPT
      from the perspective of the US health care system. METHODS: We undertook a cost
      effectiveness analysis combining estimates from the trial and the literature to
      populate the previously validated Center for Outcomes Research (CORE) Diabetes
      Model. Results represent the use of 3-day sensors, as in the trial, and 6-day
      sensors, approved in most markets but not yet approved in the United States.
      RESULTS: Within-trial hospital days, emergency department visits, and outpatient
      visits did not differ significantly between the treatment groups. Assuming 65%
      use of 3-day sensors, treatment-related costs in year 1 were an estimated $10,760
      for SAPT and $5072 for MDI. Discounted lifetime estimates were $253,493 in direct
      medical costs and 10.794 quality-adjusted life-years (QALYs) for SAPT and
      $167,170 in direct medical costs and 10.418 QALYs for MDI. For 3-day and 6-day
      sensors, the incremental cost-effectiveness ratios were $229,675 per QALY (95%
      confidence interval $139,071-$720,865) and $168,104 per QALY (95% confidence
      interval $102,819-$523,161), respectively. The ratios ranged from $69,837 to
      $211,113 per QALY with different strategies for incorporating utility benefits
      resulting from less fear of hypoglycemia with SAPT. CONCLUSION: Despite superior
      clinical benefits of SAPT compared with MDI, SAPT does not appear to be
      economically attractive in the United States for adults with type 1 diabetes in
      its current state of development. However, further clinical developments reducing
      disposable costs of the system could significantly improve its economic
      attractiveness.

PMID- 22867772
TI  - Deriving input parameters for cost-effectiveness modeling: taxonomy of data types
      and approaches to their statistical synthesis.
AB  - BACKGROUND: The evidence base informing economic evaluation models is rarely
      derived from a single source. Researchers are typically expected to identify and
      combine available data to inform the estimation of model parameters for a
      particular decision problem. The absence of clear guidelines on what data can be
      used and how to effectively synthesize this evidence base under different
      scenarios inevitably leads to different approaches being used by different
      modelers. OBJECTIVES: The aim of this article is to produce a taxonomy that can
      help modelers identify the most appropriate methods to use when synthesizing the
      available data for a given model parameter. METHODS: This article developed a
      taxonomy based on possible scenarios faced by the analyst when dealing with the
      available evidence. While mainly focusing on clinical effectiveness parameters,
      this article also discusses strategies relevant to other key input parameters in
      any economic model (i.e., disease natural history, resource use/costs, and
      preferences). RESULTS: The taxonomy categorizes the evidence base for health
      economic modeling according to whether 1) single or multiple data sources are
      available, 2) individual or aggregate data are available (or both), or 3)
      individual or multiple decision model parameters are to be estimated from the
      data. References to examples of the key methodological developments for each
      entry in the taxonomy together with citations to where such methods have been
      used in practice are provided throughout. CONCLUSIONS: The use of the taxonomy
      developed in this article hopes to improve the quality of the synthesis of
      evidence informing decision models by bringing to the attention of health
      economics modelers recent methodological developments in this field.

PMID- 22867774
TI  - Inverse probability weighted least squares regression in the analysis of time
      censored cost data: an evaluation of the approach using SEER-Medicare.
AB  - OBJECTIVES: To assess the accuracy and precision of inverse probability weighted
      (IPW) least squares regression analysis for censored cost data. METHODS: By using
      Surveillance, Epidemiology, and End Results-Medicare, we identified 1500 breast
      cancer patients who died and had complete cost information within the database.
      Patients were followed for up to 48 months (partitions) after diagnosis, and
      their actual total cost was calculated in each partition. We then simulated
      patterns of administrative and dropout censoring and also added censoring to
      patients receiving chemotherapy to simulate comparing a newer to older
      intervention. For each censoring simulation, we performed 1000 IPW regression
      analyses (bootstrap, sampling with replacement), calculated the average value of
      each coefficient in each partition, and summed the coefficients for each
      regression parameter to obtain the cumulative values from 1 to 48 months.
      RESULTS: The cumulative, 48-month, average cost was $67,796 (95% confidence
      interval [CI] $58,454-$78,291) with no censoring, $66,313 (95% CI $54,975
      $80,074) with administrative censoring, and $66,765 (95% CI $54,510-$81,843) with
      administrative plus dropout censoring. In multivariate analysis, chemotherapy was
      associated with increased cost of $25,325 (95% CI $17,549-$32,827) compared with
      $28,937 (95% CI $20,510-$37,088) with administrative censoring and $29,593
      ($20,564-$39,399) with administrative plus dropout censoring. Adding censoring to
      the chemotherapy group resulted in less accurate IPW estimates. This was
      ameliorated, however, by applying IPW within treatment groups. CONCLUSION: IPW is
      a consistent estimator of population mean costs if the weight is correctly
      specified. If the censoring distribution depends on some covariates, a model that
      accommodates this dependency must be correctly specified in IPW to obtain
      accurate estimates.

PMID- 22867773
TI  - Development of a database of instruments for resource-use measurement: purpose,
      feasibility, and design.
AB  - BACKGROUND: Health economists frequently rely on methods based on patient recall
      to estimate resource utilization. Access to questionnaires and diaries, however,
      is often limited. This study examined the feasibility of establishing an open
      access Database of Instruments for Resource-Use Measurement, identified relevant
      fields for data extraction, and outlined its design. METHODS: An electronic
      survey was sent to authors of full UK economic evaluations listed in the National
      Health Service Economic Evaluation Database (2008-2010), authors of monographs of
      Health Technology Assessments (1998-2010), and subscribers to the JISCMail health
      economics e-mailing list. The survey included questions on piloting, validation,
      recall period, and data capture method. Responses were analyzed and data
      extracted to generate relevant fields for the database. RESULTS: A total of 143
      responses to the survey provided data on 54 resource-use instruments for
      inclusion in the database. All were reliant on patient or carer recall, and a
      majority (47) were questionnaires. Thirty-seven were designed for self-completion
      by the patient, carer, or guardian, and the remainder were designed for
      completion by researchers or health care professionals while interviewing
      patients. Methods of development were diverse, particularly in areas such as the
      planning of resource itemization (evident in 25 instruments), piloting (25), and
      validation (29). CONCLUSION: On the basis of the present analysis, we developed a
      Web-enabled Database of Instruments for Resource-Use Measurement, accessible via
      www.DIRUM.org. This database may serve as a practical resource for health
      economists, as well as a means to facilitate further research in the area of
      resource-use data collection.

PMID- 22867775
TI  - Switching from originator brand medicines to generic equivalents in selected
      developing countries: how much could be saved?
AB  - OBJECTIVES: In low- and middle-income countries, patients and reimbursement
      agencies that purchase medicines in the private sector pay more for originator
      brands when generic equivalents exist. We estimated the savings that could be
      obtained from a hypothetical switch in medicine consumption from originator
      brands to lowest-priced generic equivalents for a selection of medicines in 17
      countries. METHODS: In this cost minimization analysis, the prices of originator
      brands and their lowest-priced generic equivalents were obtained from facility
      based surveys conducted by using a standard methodology. Fourteen medicines most
      commonly included in the surveys, plus three statins, were included in the
      analysis. For each medicine, the volume of private sector consumption of the
      originator brand product was obtained from IMS Health, Inc. Volumes were applied
      to the median unit prices for both originator brands and their lowest-priced
      generics to estimate cost savings. Prices were adjusted to 2008 by using consumer
      price index data and were adjusted for purchasing power parity. RESULTS: For the
      medicines studied, an average of 9% to 89% could be saved by an individual
      country from a switch in private sector purchases from originator brands to
      lowest-priced generics. In public hospitals in China, US $ 370 million could be
      saved from switching only four medicines, saving an average of 65%. Across
      individual medicines, average potential savings ranged from 11% for beclometasone
      inhaler to 73% for ceftriaxone injection. CONCLUSIONS: Substantial savings could
      be achieved by switching private sector purchases from originator brand medicines
      to lowest-priced generic equivalents. Strategies to promote generic uptake, such
      as generic substitution by pharmacists and increasing confidence in generics by
      professionals and the public, should be included in national medicines policies.

PMID- 22867776
TI  - Validation of the UFS-QOL-hysterectomy questionnaire: modifying an existing
      measure for comparative effectiveness research.
AB  - OBJECTIVE: The Uterine Fibroid Symptom and Quality of Life (UFS-QOL)
      questionnaire, a validated patient-reported outcome measure of fibroid symptoms
      and health-related quality of life, was modified for use posthysterectomy. This
      study was conducted to psychometrically validate the UFS-QOL-Hysterectomy
      questionnaire for potential use in comparative effectiveness research to evaluate
      uterine fibroid treatments. METHODS: This multicenter prospective study enrolled
      premenopausal women aged 30 to 50 years with uterine fibroids who were scheduled
      for hysterectomy, myomectomy, or uterine fibroid embolization. All participants
      completed the UFS-QOL questionnaire and short form 36 health survey at baseline
      prior to treatment and 6 and 12 months postprocedure. Women with hysterectomy
      completed the UFS-QOL-Hysterectomy questionnaire during follow-up visits.
      Internal consistency reliability, discriminant and concurrent validity, and
      responsiveness were assessed. RESULTS: A total of 274 women were enrolled (107
      uterine fibroid embolization, 61 myomectomy, and 106 hysterectomy) and 89 (83%),
      55 (90%), and 91 (86%), respectively, completed the 12-month follow-up. The mean
      age was 43.2 (uterine fibroid embolization), 40.6 (myomectomy), and 44.5
      (hysterectomy) years; 53%, 43%, and 37%, respectively, were black. Cronbach's
      alphas for the UFS-QOL-Hysterectomy questionnaire at 6 months ranged from 0.70 to
      0.96 and from 0.66 to 0.95 at 12 months. Effect sizes ranged from 1.23 to 2.55,
      indicating that the UFS-QOL-Hysterectomy questionnaire was highly responsive.
      CONCLUSIONS: The UFS-QOL-Hysterectomy questionnaire is a valid and reliable
      patient-reported outcome measure of uterine fibroid treatment with hysterectomy
      and can be used in conjunction with the UFS-QOL questionnaire to compare patient
      reported outcomes across treatments.

PMID- 22867777
TI  - Combining individual-level discrete choice experiment estimates and costs to
      inform health care management decisions about customized care: the case of follow
      up strategies after breast cancer treatment.
AB  - OBJECTIVE: Customized care can be beneficial for patients when preferences for
      health care programs are heterogeneous. Yet, there is little guidance on how
      individual-specific preferences and cost data can be combined to inform health
      care decisions about customized care. Therefore, we propose a discrete choice
      experiment-based approach that illustrates how to analyze the cost-effectiveness
      of customized (and noncustomized) care programs to provide information for
      hospital managers. METHODS: We exploit the fact that choice models make it
      possible to determine whether preference heterogeneity exists and to obtain
      individual-specific parameter estimates. We present an approach of how to combine
      these individual-specific parameter estimates from a random parameter model
      (mixed logit model) with cost data to analyze the cost-effectiveness of
      customized care and demonstrate our method in the case of follow-up after breast
      cancer treatment. RESULTS: We found that there is significant preference
      heterogeneity for all except two attributes of breast cancer treatment follow-up
      and that the fully customized care program leads to higher utility and lower
      costs than the current standardized program. Compared with the single alternative
      program, the fully customized care program has increased benefits and higher
      costs. Thus, it is necessary for health care decision makers to judge whether the
      use of resources for customized care is cost-effective. CONCLUSIONS: Decision
      makers should consider using the results obtained from our methodological
      approach when they consider implementing customized health care programs, because
      it may help to find ways to save costs and increase patient satisfaction.

PMID- 22867778
TI  - Does responsibility affect the public's valuation of health care interventions? A
      relative valuation approach to health care safety.
AB  - OBJECTIVE: Health services often spend more on safety interventions than seems
      cost-effective. This study investigates whether the public value safety-related
      health care improvements more highly than the same improvements in contexts where
      the health care system is not responsible. METHOD: An online survey was conducted
      to elicit the relative importance placed on preventing harms caused by 1) health
      care (hospital-acquired infections, drug administration errors, injuries to
      health care staff), 2) individuals (personal lifestyle choices, sports-related
      injuries), and 3) nature (genetic disorders). Direct valuations were obtained
      from members of the public by using a person trade-off or "matching" method.
      Participants were asked to choose between two preventative interventions of equal
      cost and equal health benefit per person for the same number of people, but
      differing in causation. If participants indicated a preference, their strength of
      preference was measured by using person trade-off. RESULTS: Responses were
      obtained from 1030 people, reflecting the sociodemographic mix of the UK
      population. Participants valued interventions preventing hospital-acquired
      infections (1.31) more highly than genetic disorders (1.0), although drug errors
      were valued similarly to genetic disorders (1.07), and interventions to prevent
      injury to health care staff were given less weight than genetic disorders (0.71).
      Less weight was also given to interventions related to lifestyle (0.65) and
      sports injuries (0.41). CONCLUSION: Our results suggest that people do not attach
      a simple fixed premium to "safety-related" interventions but that preferences
      depend more subtly on context. The use of the results of such public preference
      surveys to directly inform policy would therefore be premature.

PMID- 22867779
TI  - Valuing the extended role of prescribing pharmacist in general practice: results
      from a discrete choice experiment.
AB  - OBJECTIVES: To quantify patients' preferences for new pharmacist independent
      prescribing services in general practice for managing common existing long-term
      conditions compared with usual medical prescribing. METHODS: A discrete choice
      experiment cross-sectional survey was conducted in five general practices in
      England (October-November 2009). Four service attributes reported on the length
      of consultation and aspects of patient-professional interaction. A choice between
      three alternatives-novel pharmacist independent prescribing service ("prescribing
      pharmacist"), "own (family) doctor" service, and "available (family) doctor"
      service-was presented. Alternative regression models were compared according to
      their goodness of fit, and the preferred one was used to inform policy analysis.
      RESULTS: A total of 451 patients completed questionnaires. Respondents preferred
      a "pharmacist" or "own doctor" compared with "available doctor," with a larger
      value given to own doctor. All attributes on patient-professional interaction
      were important in choosing how to manage diagnosed hypertension, while the
      "length of consultation" (P = 0.42) did not have any impact. The impact of
      introducing a pharmacist prescribing service into a general practice setting was
      estimated from these findings. Patients' preferences suggested that about 16% of
      consultations with a patient's own doctor can be switched to a prescribing
      pharmacist instead. Although there is a stronger preference for seeing own
      doctor, alternative combinations of attribute levels can be used to compensate
      and reconfigure a more preferred prescribing pharmacist service. CONCLUSIONS: The
      pharmacist service is valued by patients as an alternative to doctor prescribing
      in primary care and therefore represents an acceptable form of service delivery
      when informing policy.

PMID- 22867780
TI  - Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets.
AB  - BACKGROUND: A five-level version of the EuroQol five-dimensional (EQ-5D)
      descriptive system (EQ-5D-5L) has been developed, but value sets based on
      preferences directly elicited from representative general population samples are
      not yet available. The objective of this study was to develop values sets for the
      EQ-5D-5L by means of a mapping ("crosswalk") approach to the currently available
      three-level version of the EQ-5D (EQ-5D-3L) values sets. METHODS: The EQ-5D-3L
      and EQ-5D-5L descriptive systems were coadministered to respondents with
      conditions of varying severity to ensure a broad range of levels of health across
      EQ-5D questionnaire dimensions. We explored four models to generate value sets
      for the EQ-5D-5L: linear regression, nonparametric statistics, ordered logistic
      regression, and item-response theory. Criteria for the preferred model included
      theoretical background, statistical fit, predictive power, and parsimony.
      RESULTS: A total of 3691 respondents were included. All models had similar fit
      statistics. Predictive power was slightly better for the nonparametric and
      ordered logistic regression models. In considering all criteria, the
      nonparametric model was selected as most suitable for generating values for the
      EQ-5D-5L. CONCLUSIONS: The nonparametric model was preferred for its simplicity
      while performing similarly to the other models. Being independent of the value
      set that is used, it can be applied to transform any EQ-5D-3L value set into EQ
      5D-5L index values. Strengths of this approach include compatibility with three
      level value sets. A limitation of any crosswalk is that the range of index values
      is restricted to the range of the EQ-5D-3L value sets.

PMID- 22867781
TI  - Willingness to pay for prostate cancer treatment among patients and their family
      members at 1 year after diagnosis.
AB  - OBJECTIVES: To explore an alternative approach to quantifying the burden of side
      effects at 1 year after treatment for prostate cancer among both patients and
      their partners. METHODS: We analyzed data from 75 couples in the Family and
      Cancer Therapy Selection study. Paired patients and family members were
      independently asked about their willingness to pay (WTP) for a hypothetical new
      treatment that cures prostate cancer without side effects if they could
      reconsider their treatment decision by indicating the maximum amount they would
      be willing to pay given 11 separate "bids" ranging from $0 to $1500 per month.
      Descriptive and regression analyses were conducted for patients and family
      members controlling for sociodemographic characteristics and health status;
      Spearman correlations were also examined. RESULTS: Among 75 couples analyzed, the
      income-adjusted mean WTP estimates per month were $400.8 (standard error [SE]
      $54.3) for patients and $650.2 (SE 72.2) for family members. The WTP between
      patients and family members was correlated (Pearson rho 0.30; P = 0.01). After
      adjusting for covariates, the adjusted mean WTP per month was $588.1 (SE 65.77)
      for patients and $819.4 (SE 74.33) for family members. Wanting to avoid side
      effects at baseline predicted higher WTP for patients (P = 0.010). Experiencing
      sexual side effects was predictive of higher WTP for family members (P = 0.047).
      CONCLUSIONS: Fairly high WTP amounts for a hypothetical treatment without side
      effects suggests that patients and their partners are experiencing important
      burdens 1 year after treatment. The higher amounts partners are willing to pay
      and the correlation with sexual side effects suggest that they are perceptive of
      significant treatment burdens.

PMID- 22867782
TI  - Modeling the risks and benefits of depression treatment for children and young
      adults.
AB  - OBJECTIVES: To quantify the trade-offs of alternative strategies in treating
      pediatric major depressive disorder with respect to the clinical benefit and risk
      of fatal and nonfatal suicidal behavior over a 5-year time horizon. METHODS: We
      developed a disease simulation model integrating epidemiological and clinical
      data from the literature to simulate the effect of selective serotonin reuptake
      inhibitors (SSRIs), cognitive behavioral therapy (CBT), and a combination of both
      on a US pediatric population with major depressive disorder. RESULTS: In a cohort
      of 1,000,000 simulated individuals (ages 10-24 years), the use of SSRIs was
      associated with the highest number of suicide-related events, while CBT was
      associated with the lowest number. Over a 5-year period, the strategy with the
      highest number of symptom-free weeks depended on assumptions made regarding
      treatment efficacy beyond the available clinical data. CONCLUSIONS: Considering
      the risk-benefit profile over a 5-year period, CBT offers a safer profile than
      combination treatment or SSRIs alone with respect to suicide deaths and attempts.
      Any additional benefits of SSRIs, either alone or in combination with CBT, must
      be weighed against the expected increase in suicides.

PMID- 22867783
TI  - Whose values in health? An empirical comparison of the application of adolescent
      and adult values for the CHU-9D and AQOL-6D in the Australian adolescent general
      population.
AB  - OBJECTIVES: The Child Health Utility-9D (CHU-9D) and the Assessment of Quality of
      Life-6D (AQOL-6D) presently represent the only two generic preference-based
      instruments developed for application with young people with both adult- and
      adolescent-specific scoring algorithms. The main objective of this study was to
      compare and contrast the application of adult and adolescent scoring algorithms
      for the CHU-9D and AQOL-6D in valuing the health of a community-based sample of
      adolescents. METHODS: A Web-based survey including the CHU-9D and the AQOL-6D was
      developed for administration to adolescents, aged 11 to 17 years, residing in
      Australia (n = 500). Individual responses to both instruments were converted to
      values by using first the adult and second the adolescent scoring algorithms
      pertaining to each instrument. RESULTS: Both the AQOL-6D and the CHU-9D
      discriminated well according to health status and the presence of long-standing
      illness regardless of the scoring algorithm. Within each instrument, however,
      important discrepancies were found in that employment of the adolescent algorithm
      was found to result in consistently lower mean health state values for the CHU-9D
      but consistently higher mean health state values for the AQOL-6D relative to the
      employment of their respective adult algorithms and these differences were
      statistically significant (P < 0.05). CONCLUSION: The differences in adolescent
      and adult values for identical health states are more profound for the CHU-9D and
      ultimately may be significant enough to have an impact on health care policy. It
      is important to note that there are important differences between the CHU-9D
      instrument and the AQOL-6D instrument that may also have a significant impact on
      the valuations obtained.

PMID- 22867784
TI  - Financial risk-sharing in updating the National List of Health Services in
      Israel: stakeholders' perceived interests.
AB  - OBJECTIVES: Risk-sharing is being considered by many health care systems to
      address the financial risk associated with the adoption of new technologies. We
      explored major stakeholders' views toward the potential implementation of a
      financial risk-sharing mechanism regarding budget-impact estimates for adding new
      technologies to the Israeli National List of Health Services. According to our
      proposed scheme, health plans will be partially compensated by technology
      sponsors if the actual use of a technology is substantially higher than what was
      projected and health plans will refund the government for budgets that were not
      fully utilized. METHODS: By using a semi-structured protocol, we interviewed
      major stakeholders involved in the process of updating the National List of
      Health Services (N = 31). We inquired into participants' views toward our
      proposed risk-sharing mechanism, whether the proposed scheme would achieve its
      purpose, its feasibility of implementation, and their opinion on the other
      stakeholders' incentives. RESULTS: Participants' considerations were classified
      into four main areas: financial, administrative/managerial, impact on patients'
      health, and influence on public image. Most participants agreed that the
      conceptual risk-sharing scheme will improve the accuracy of early budget
      estimates and were in favor of the proposed scheme, although Ministry of Finance
      officials tended to object to it. CONCLUSIONS: The successful implementation of
      risk-sharing schemes depends mainly on their perception as a win-win situation by
      all stakeholders. The perception exposed by our participants that risk-sharing
      can be a tool for improving the accuracy of early budget-impact estimates and the
      challenges pointed by them are relevant to other health care systems also and
      should be considered when implementing similar schemes.

PMID- 22867785
TI  - How do insured perceive their financial security in the event of illness?--a
      panel data analysis for Germany.
AB  - OBJECTIVE: There is a lack of research regarding the subjective perception of
      financial security in the event of illness of insured persons. Therefore, the aim
      of our study was to analyze the subjective perception of financial security in
      the event of illness in the German setting over time and to identify major
      determinants of that perception. METHODS: We applied a probit-adapted ordinary
      least squares estimation procedure including fixed effects to a balanced data set
      from the German Socio-Economic Panel. After correcting our data set, we included
      approximately 23,500 observations in our analyses. RESULTS: We show that higher
      income and the existence of private health insurance have a positive and
      significant impact on the perception of financial security. Furthermore, private
      supplementary health insurance has a positive and significant effect on this
      perception; however, this is solely true for policies that cover special features
      during hospital stays. Experience with the health care system is also positively
      related to the individual's perception. Finally, our regression results
      illustrate that the overall perception is declining over time. CONCLUSIONS: The
      results indicate that political decision makers are facing challenges regarding
      the declining subjective perception in the German health care system. Because of
      the positive correlation between experience and subjective perception, it can be
      assumed that the health care system and especially statutory health insurance are
      better than their presentation in the media. Hence, there is a problem of
      communication and information, and political decision makers face challenges in
      presenting the system objectively and handling the media in a proper way.

PMID- 22867786
TI  - The maximum willingness to pay for smoking cessation method among adult smokers
      in Mexico.
AB  - OBJECTIVES: To estimate the maximum willingness to pay (WTP) for an effective
      smoking cessation treatment among smokers in Mexico and to identify the
      environmental, demographic, and socioeconomic factors associated with the WTP.
      METHODS: A cross-sectional study was conducted. The sample contained 777 smokers
      (willingness to quit using a WTP of >0) who had responded to the 2009 Global
      Adult Tobacco Survey conducted in Mexico. Statistical associations and
      descriptive analyses were conducted to describe smokers and their WTP by using
      tobacco-related environmental, socioeconomic, and demographic variables. RESULTS:
      Overall, 74.4% of the smokers were men and 51.4% were daily smokers. On average,
      the smokers had been consuming tobacco for more than 15 years, 58.6% had made
      cessation attempts in the past, and around 10.0% knew about the existence of
      centers to aid in smoking cessation. The average WTP for an effective cessation
      method was US $191. Among men, the WTP was US $152 lower than among women. In all
      the estimated models, the higher an individual's education and socioeconomic
      level, the higher his or her WTP. CONCLUSIONS: This study suggests that Mexican
      smokers interested in quitting smoking attribute a high monetary value to an
      effective cessation method. Male smokers demonstrated less altruistic behavior
      than did female smokers. Mexico requires the implementation of more policies
      designed to support smoking cessation and to limit tobacco addiction. Expanding
      the availability of cessation programs and access to pharmacological treatments
      may contribute to reaching universal coverage by integrating new pharmacological
      alternatives into the health sector's medicine formulary.

PMID- 22867787
TI  - Bendamustine versus chlorambucil for the first-line treatment of chronic
      lymphocytic leukemia in England and Wales: a cost-utility analysis.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of bendamustine compared with
      chlorambucil as first-line treatment for patients with chronic lymphocytic
      leukemia who would be considered unsuitable for treatment with fludarabine
      combination chemotherapy regimens. METHODS: A semi-Markov approach was used to
      estimate time in each health state. The model was parameterized primarily by
      using data from a phase III randomized, open-label trial comparing bendamustine
      with chlorambucil. It captured the increased progression-free survival and
      improved response rates with bendamustine, and the cost and quality of life
      impacts of postprogression treatments. The analysis was conducted from the
      perspective of the National Health Service in England and Wales. A lifetime (35
      year) time horizon was used. Deterministic sensitivity analyses, probabilistic
      sensitivity analyses, and subgroup analyses in older patients and patients with
      poor performance status were carried out. RESULTS: The estimated incremental cost
      effectiveness ratio was L 11,960 per quality-adjusted life-year. None of the
      deterministic sensitivity analyses increased the incremental cost-effectiveness
      ratio by more than L 2000. Subgroup analyses showed that bendamustine remained
      cost-effective across different patient groups. Probabilistic sensitivity
      analysis showed that at the L 20,000 threshold, bendamustine has a 90%
      probability of being cost-effective. CONCLUSIONS: Bendamustine represents good
      value for first-line treatment of patients with chronic lymphocytic leukemia who
      are unsuitable for treatment with fludarabine combination chemotherapy. The
      incremental cost-effectiveness ratio is below the thresholds commonly applied in
      England and Wales (L 20,000-L 30,000 per quality-adjusted life-year).

PMID- 22867788
TI  - Economic evaluation and the Jordan Rational Drug List: an exploratory study of
      national-level priority setting.
AB  - OBJECTIVES: To explore the extent of and barriers to the use of economic
      evaluation in compiling the Jordan Rational Drug List in the health care system
      of Jordan. METHODS: The research reported in this article involved a case study
      of the Jordan Rational Drug List. Data collection methods included semi
      structured interviews with decision makers and analysis of secondary documentary
      sources. The case study was supplemented by additional interviews with a small
      number of Jordanian academics involved in the production of economic evaluation.
      RESULTS: The research found that there was no formal requirement for cost
      effectiveness information submitted as part of the decision-making process for
      the inclusion of new technologies on the Jordan Rational Drug List. Both decision
      makers and academics suggested that economic evidence was not influential in
      formulary decisions. This is unusual for national formulary bodies. The study
      identified a number of barriers that prevent substantive and routine use of
      economic evaluation. While some of these echo findings of previous studies,
      others-notably the extent to which the sectional interests of clinical groups and
      commercial (pharmaceutical) industry exert undue influence over decision making
      more obviously result from the specific Jordanian context. CONCLUSIONS: Economic
      evaluation was not found to be influential in the Jordan Rational Drug List.
      Recommendations for improvement include enhancing capacity in relation to
      generating, accessing, and/or applying health economic analysis to priority
      setting decisions. There is a further need to incentivize the use of economic
      evaluation, and this requires that organizational and structural impediments be
      removed.

PMID- 22867789
TI  - Time trade-off and ranking exercises are sensitive to different dimensions of EQ
      5D health states.
AB  - BACKGROUND: One method suggested for creating preference-based tariffs for the
      new five-level EuroQol five-dimensional (EQ-5D) questionnaire is combining time
      trade-off (TTO) and discrete choice exercises. Rank values from previous
      valuation studies can be used as proxies for discrete choice exercises. This
      study examined rank and TTO data to determine whether the methods differ in
      sensitivity to the EQ-5D questionnaire dimensions. METHODS: We used rank and TTO
      data for 42 EQ-5D questionnaire health states from the US and UK three-level EQ
      5D questionnaire valuation studies, extracting overall ranks of mean TTO and mean
      rank values, ranging from 1 (best) to 42 (worst). We identified pairs of health
      states with reversed overall ranks between TTO and rank data and regressed
      overall rank differences (TTO - ranking) on dummy variables representing
      impairments on EQ-5D questionnaire dimensions. RESULTS: Forty-three (US) and 41
      (UK) health state pairs displayed reversed rank order. Both US and UK regression
      models on rank differences indicated that respondents rated impairments involving
      pain/discomfort and anxiety/depression as relatively worse in TTO than in the
      ranking task. DISCUSSION: Different dimension sensitivity between TTO and ranking
      methods suggests that combining them could lead to inconsistent tariffs.
      Differences could be caused by respondents focusing on the first presented
      dimensions when ranking states or could be related to the longest endurable time
      for health states involving pain/discomfort or anxiety/depression. The observed
      differences call into question which method best represents the preferences of
      the population.

PMID- 22867790
TI  - Approach to fixing the discrepancy found in the Wu et al. FACT-P to EQ-5D
      questionnaire mapping algorithm.

PMID- 22867792
TI  - Improving the measurement of QALYs in dementia: some important considerations.

PMID- 22867794
TI  - Molecular cloning and characterization of (+)-epi-alpha-bisabolol synthase,
      catalyzing the first step in the biosynthesis of the natural sweetener,
      hernandulcin, in Lippia dulcis.
AB  - Hernandulcin, a C15 sesquiterpene ketone, is a natural sweetener isolated from
      the leaves of Lippia dulcis. It is a promising sugar substitute due to its safety
      and low caloric potential. However, the biosynthesis of hernandulcin in L. dulcis
      remains unknown. The first biochemical step of hernandulcin is the synthesis of
      (+)-epi-alpha-bisabolol from farnesyl diphosphate, which is presumed to be
      catalyzed by a unique sesquiterpene synthase in L. dulcis. In order to decipher
      hernandulcin biosynthesis, deep transcript sequencings (454 and Illumina) were
      performed, which facilitated the molecular cloning of five new sesquiterpene
      synthase cDNAs from L. dulcis. In vivo activity evaluation of these cDNAs in
      yeast identified them as the sesquiterpene synthases for alpha-copaene/delta
      cadinene, bicyclogermacrene, beta-caryophyllene, trans-alpha-bergamotene, and
      alpha-bisabolol. The engineered yeast could synthesize a significant amount (~0.3
      mg per mL) of alpha-bisabolol in shake-flask cultivation. This efficient in vivo
      production was congruent with the competent kinetic properties of recombinant
      alpha-bisabolol synthase (K(m) 4.8 MUM and k(cat) 0.04 s(-1)). Detailed chemical
      analyses of the biosynthesized alpha-bisabolol confirmed its configuration to be
      (+)-epi-alpha-bisabolol, the core skeleton of hernandulcin. These results
      demonstrated that enzymatic, stereoselective synthesis of (+)-epi-alpha-bisabolol
      can be achieved, promising the heterologous production of a natural sweetener,
      hernandulcin.

PMID- 22867795
TI  - Analyses of methionine sulfoxide reductase activities towards free and peptidyl
      methionine sulfoxides.
AB  - There have been insufficient kinetic data that enable a direct comparison between
      free and peptide methionine sulfoxide reductase activities of either MsrB or
      MsrA. In this study, we determined the kinetic parameters of mammalian and yeast
      MsrBs and MsrAs for the reduction of both free methionine sulfoxide (Met-O) and
      peptidyl Met-O under the same assay conditions. Catalytic efficiency of mammalian
      and yeast MsrBs towards free Met-O was >2000-fold lower than that of yeast fRMsr,
      which is specific for free Met-R-O. The ratio of free to peptide Msr activity in
      MsrBs was 1:20-40. In contrast, mammalian and yeast MsrAs reduced free Met-O much
      more efficiently than MsrBs. Their k(cat) values were 40-500-fold greater than
      those of the corresponding MsrBs. The ratio of free to peptide Msr activity was
      1:0.8 in yeast MsrA, indicating that this enzyme can reduce free Met-O as
      efficiently as peptidyl Met-O. In addition, we analyzed the in vivo free Msr
      activities of MsrBs and MsrAs in yeast cells using a growth complementation
      assay. Mammalian and yeast MsrBs, as well as the corresponding MsrAs, had
      apparent in vivo free Msr activities. The in vivo free Msr activities of MsrBs
      and MsrAs agreed with their in vitro activities.

PMID- 22867796
TI  - A simple assay for 6-aminohexanoate-oligomer-hydrolase using N-(4-nitrophenyl)-6
      aminohexanamide.
AB  - We synthesized N-(4-nitrophenyl)-6-aminohexanamide (AHpNA) and used it as a
      substrate in a kinetic study of 6-aminohexanoate-hydrolase (NylB), a nylon
      oligomer-hydrolyzing enzyme. NylBs derived from Arthrobacter sp. KI72 and
      Pseudomonas sp. NK87 hydrolyzed AHpNA as well as a 6-aminohexanoic acid dimer, a
      known substrate for NylB. The K(m) values of the NylB from Arthrobacter sp. KI72
      and Pseudomonas sp. NK87 for AHpNA were 0.5 mM and 2.0 mM, respectively.

PMID- 22867797
TI  - Improvement of multiple stress tolerance in yeast strain by sequential
      mutagenesis for enhanced bioethanol production.
AB  - The present work deals with the improvement of multiple stress tolerance in a
      glucose-xylose co-fermenting hybrid yeast strain RPR39 by sequential mutagenesis
      using ethyl methane sulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, near and far
      ultraviolet radiations. The mutants were evaluated for their tolerance to
      ethanol, temperature and fermentation inhibitors. Among these mutants, mutant
      RPRT90 exhibited highest tolerance to 10% initial ethanol concentration, 2 g L(
      1) furfural and 8 g L(-1) acetic acid. The mutant also showed good growth at high
      temperature (39-40 degrees C). A study on the combined effect of multiple
      stresses during fermentation of glucose-xylose mixture (3:1 ratio) was performed
      using mutant RPRT90. Under the combined effect of thermal (39 degrees C) and
      inhibitor stress (0.25 g L(-1) vanillin, 0.5 g L(-1) furfural and 4 g L(-1)
      acetic acid), the mutant produced ethanol with a yield of 0.379 g g(-1), while
      under combined effect of ethanol (7% v/v) and inhibitor stress the ethanol yield
      obtained was 0.43 g g(-1). Further, under the synergistic effect of sugar (250 g
      L(-1)), thermal (39 degrees C), ethanol (7% v/v) and inhibitors stress, the
      strain produced a maximum of 47.93 g L(-1) ethanol by utilizing 162.42 g L(-1) of
      glucose-xylose mixture giving an ethanol yield of 0.295 g g(-1) and productivity
      of 0.57 g L(-1) h(-1). Under same condition the fusant RPR39 produced a maximum
      of 30.0 g L(-1) ethanol giving a yield and productivity of 0.21 g g(-1) and 0.42
      g L(-1) h(-1) respectively. The molecular characterization of mutant showed
      considerable difference in its genetic profile from hybrid RPR39. Thus,
      sequential mutagenesis was found to be effective to improve the stress tolerance
      properties in yeast.

PMID- 22867798
TI  - Antinociceptive effects of tramadol in co-administration with  metamizol after
      single and repeated administrations in rats.
AB  - Combinations of two analgesic drugs of the same or different class are widely
      used in clinical therapy to enhance its antinociceptive effects and reduce the
      side effects. In order to evaluate a possible antinociceptive synergistic
      interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and
      tramadol s.c., an atypical opioid (opioid receptor agonist), were administered
      alone or in combination. In the present study, the antinociceptive efficacy and
      the possible development of pharmacological tolerance produced by the combination
      tramadol plus metamizol during a 4-day treatment in rats using the plantar test
      was evaluated. Male Wistar rats were s.c. injected with tramadol (17.8 mg/kg),
      metamizol (177.8 mg/kg) or the combination tramadol plus metamizol three times a
      day for 4 days. Both metamizol and tramadol produced antinociceptive effects with
      a low rate trend towards tolerance development at the end of the treatment. The
      antinociceptive efficacy of tramadol and metamizol co-administration gradually
      decreased after the second injection. These data suggest that when the
      combination is given in a unique administration it results in an important
      potentiation of their individual antinociceptive effects. But, the repeated
      coadministration of tramadol plus metamizol results in a development of
      tolerance.

PMID- 22867799
TI  - HYP-1, a novel diamide compound, relieves inflammatory and neuropathic pain in
      rats.
AB  - In the present study, we investigated whether a novel compound, 2-(2-(4-((4
      chlorophenyl)(phenyl)methyl) piperazin-1-yl)-2-oxoethylamino)-N-(3,4,5
      trimethoxybenzyl)acetamide (HYP-1), is capable of binding to voltage-gated sodium
      channels (VGSCs) and evaluated both its inhibitory effect on Na+ currents of the
      rat dorsal root ganglia (DRG) sensory neuron and its in vivo analgesic activity
      using rat models of inflammatory and neuropathic pain. HYP-1 showed not only high
      affinity for rat sodium channel (site 2), but also potent inhibitory activity
      against the TTX-R Na+ currents of the rat DRG sensory neuron. HYP-1 co-injected
      with formalin (5%, 50 MUl) under the plantar surface of rat hind paw dose
      dependently reduced spontaneous pain behaviors during both the early and late
      phases. This result was confirmed by c-Fos immunofluorescence in the L4-5 spinal
      segments. A large number of c-Fos-positive neurons were observed in rat injected
      with a mixture of formalin and vehicle, but not in rat treated with a mixture of
      formalin and HYP-1. In addition, the effectiveness of HYP-1 (6 and 60 mg/kg,
      i.p.) in suppression of neuropathic pain, such as mechanical, cold and warm
      allodynia, induced by rat tail nerve injury was investigated. HYP-1 showed
      limited selectivity over hERG, N-type and T-type channels.Our present results
      indicate that HYP-1, as a VGSC blocker, has potential analgesic activities
      against nociceptive, inflammatory and neuropathic pain.

PMID- 22867800
TI  - Reliability studies of incident coding systems in high hazard industries: A
      narrative review of study methodology.
AB  - This paper reviews the current literature on incident coding system reliability
      and discusses the methods applied in the conduct and measurement of reliability.
      The search strategy targeted three electronic databases using a list of search
      terms and the results were examined for relevance, including any additional
      relevant articles from the bibliographies. Twenty five papers met the relevance
      criteria and their methods are discussed. Disagreements in the selection of
      methods between reliability researchers are highlighted as are the effects of
      method selection on the outcome of the trials. The review provides evidence that
      the meaningfulness of and confidence in results is directly affected by the
      methodologies employed by the researcher during the preparation, conduct and
      analysis of the reliability study. Furthermore, the review highlights the
      heterogeneity of methodologies employed by researchers measuring reliability of
      incident coding techniques, reducing the ability to critically compare and
      appraise techniques being considered for the adoption of report coding and trend
      analysis by client organisations. It is recommended that future research focuses
      on the standardisation of reliability research and measurement within the
      incident coding domain.

PMID- 22867801
TI  - Cardiac troponin and heart failure in the era of high-sensitivity assays.
AB  - The Joint European Society of Cardiology-American College of Cardiology
      Foundation-American Heart Association-World Heart Federation Task Force for the
      Redefinition of Myocardial Infarction recommends cardiac troponin (cTn)-T as a
      first-line biomarker, and suggests the use of the 99th percentile of a reference
      population with acceptable precision (i.e. a coefficient of variance<=10%) as a
      cut-off for the diagnosis of acute myocardial infarction. Recently developed
      troponin assays fulfill this analytical precision. While conventional cTnT assays
      have often been used as a positive or negative categorical variable, stepwise
      rises in high sensitivity (Hs)-cTnT in patients presenting with chronic heart
      failure (HF) have been associated with a progressive increase in the incidence of
      cardiovascular events. Similar observations have been made in the general
      population. Hs-cTnT at baseline and during follow-up is a powerful predictor of
      cardiac events in patients with HF and in the general population. Whether it is
      the ideal biomarker remains to be confirmed, however. We review the potential
      contributions of TnT assays in the assessment of risk of HF, in HF, and in
      myocardial diseases that cause HF.

PMID- 22867802
TI  - Coronary perivascular fibrosis is associated with impairment of coronary blood
      flow in patients with non-ischemic heart failure.
AB  - BACKGROUND: Although myocardial interstitial fibrosis has been considered to play
      a pathogenic role in chronic heart failure (HF), the role of perivascular
      fibrosis, another form of fibrosis, remains to be elucidated. METHODS: We
      examined 64 consecutive patients with non-ischemic HF caused by hypertrophic
      cardiomyopathy (HCM, n=16), hypertensive heart disease (HHD, n=11), or dilated
      cardiomyopathy (DCM, n=37), diagnosed by both cardiac catheterization and
      endomyocardial biopsy (right ventricular side of the interventricular septum) in
      the Tohoku University Hospital between January 2001 and April 2009. We calculated
      the collagen volume fraction (CVF) and perivascular fibrosis ratio (PFR) in
      biopsy samples and also examined Thrombolysis in Myocardial Infarction (TIMI)
      frame count to evaluate coronary blood flow. RESULTS: There was no significant
      correlation between CVF and PFR (r(2)=0.0007). Although CVF was comparable among
      HCM, HHD, and DCM (1.11 +/- 1.04, 1.89 +/- 1.61, and 1.41 +/- 1.48,
      respectively), PFR was significantly higher in HCM than in DCM (1.78 +/- 1.09 vs.
      1.23 +/- 0.44, p<0.05). PFR was not correlated with cardiac function parameters,
      such as left ventricular (LV) ejection fraction, cardiac output, LV end-diastolic
      pressure, LV end-diastolic volume, aortic pressure, or pulmonary artery pressure.
      However, PFR was significantly correlated with coronary flow in the left anterior
      descending coronary artery (as evaluated by TIMI frame count) (r(2)=0.3351,
      p<0.0001, in all-cases combined population), but not with that in the left
      circumflex or right coronary artery. This correlation remained significant in a
      logistic regression model tested in 7 variables (body mass index, PVR, CVF,
      presence of hypertension, dyslipidemia, diabetes mellitus, and atrial
      fibrillation). CONCLUSIONS: These results indicate that coronary perivascular
      fibrosis is associated with the impairment of coronary blood flow although not
      associated with interstitial fibrosis or cardiac function, suggesting that it can
      be a new therapeutic target to improve coronary microcirculation.

PMID- 22867803
TI  - Twelve-year results of a direct-bonded partial prosthesis in a patient with
      advanced periodontitis: a clinical report.
AB  - Prosthodontic treatment for patients with advanced periodontitis is a therapeutic
      challenge. A minimally invasive technique is preferred to preserve the remaining
      mobile abutment teeth. This report describes the initial clinical treatment and
      12-year follow-up of a direct-bonded prosthesis reinforced with a cast metal
      framework, used as a conservative treatment option to replace periodontally
      involved maxillary lateral incisors.

PMID- 22867804
TI  - Fracture mode during cyclic loading of implant-supported single-tooth
      restorations.
AB  - STATEMENT OF PROBLEM: Fracture of veneering ceramics in zirconia-based
      restorations has frequently been reported. Investigation of the fracture mode of
      implant-supported ceramic restorations by using clinically relevant laboratory
      protocols is needed. PURPOSE: This study compared the mode of fracture and number
      of cyclic loads until veneering fracture when ceramic and metal ceramic
      restorations with different veneering ceramics were supported by implants.
      MATERIAL AND METHODS: Thirty-two implant-supported single-tooth restorations were
      fabricated. The test group was composed of 16 ceramic restorations of zirconia
      abutment-retained crowns with zirconia copings veneered with glass-ceramics (n=8)
      and feldspathic ceramics (n=8). The control group was composed of 16 metal
      ceramic restorations of titanium abutment-retained crowns with gold alloy copings
      veneered with glass (n=8) and feldspathic ceramics (n=8). The palatal surfaces of
      the crowns were exposed to cyclic loading of 800 N with a frequency of 2 Hz,
      which continued to 4.2 million cycles or until fracture of the copings,
      abutments, or implants. The number of cycles and the fracture modes were
      recorded. The fracture modes were analyzed by descriptive analysis and the Mann
      Whitney test (alpha=.05). The differences in loading cycles until veneering
      fracture were estimated with the Cox proportional hazards analysis. RESULTS:
      Veneering fracture was the most frequently observed fracture mode. The severity
      of fractures was significantly more in ceramic restorations than in metal ceramic
      restorations. Significantly more loading cycles until veneering fracture were
      estimated with metal ceramic restorations veneered with glass-ceramics than with
      other restorations. CONCLUSIONS: The metal ceramic restorations demonstrated
      fewer and less severe fractures and resisted more cyclic loads than the ceramic
      restorations, particularly when the metal ceramic crowns were veneered with glass
      ceramics.

PMID- 22867805
TI  - Flexural strength and the probability of failure of cold isostatic pressed
      zirconia core ceramics.
AB  - STATEMENT OF PROBLEM: The flexural strength of zirconia core ceramics must
      predictably withstand the high stresses developed during oral function. The in
      depth interpretation of strength parameters and the probability of failure during
      clinical performance could assist the clinician in selecting the optimum
      materials while planning treatment. PURPOSE: The purpose of this study was to
      evaluate the flexural strength based on survival probability and Weibull
      statistical analysis of 2 zirconia cores for ceramic restorations. MATERIAL AND
      METHODS: Twenty bar-shaped specimens were milled from 2 core ceramics, IPS e.max
      ZirCAD and Wieland ZENO Zr, and were loaded until fracture according to ISO 6872
      (3-point bending test). An independent samples t test was used to assess
      significant differences of fracture strength (alpha=.05). Weibull statistical
      analysis of the flexural strength data provided 2 parameter estimates: Weibull
      modulus (m) and characteristic strength (sigma(0)). The fractured surfaces of the
      specimens were evaluated by scanning electron microscopy (SEM) and energy
      dispersive spectroscopy (EDS). The investigation of the crystallographic state of
      the materials was performed with x-ray diffraction analysis (XRD) and Fourier
      transform infrared (FTIR) spectroscopy. RESULTS: Higher mean flexural strength
      (P<.001) and sigma(0) were recorded for WZ ceramics. However IZ ceramics
      presented a higher m value and a microstructure with fewer voids and pores. The
      fractured surfaces presented similar fractographic properties (mirror regions
      followed by hackle lines zones). Both groups primarily sustained the tetragonal
      phase of zirconia and a negligible amount of the monoclinic phase. CONCLUSIONS:
      Although both zirconia ceramics presented similar fractographic and
      crystallographic properties, the higher flexural strength of WZ ceramics was
      associated with a lower m and more voids in their microstructure. These findings
      suggest a greater scattering of strength values and a flaw distribution that are
      expected to increase failure probability.

PMID- 22867806
TI  - Fracture load of zirconia crowns according to the thickness and marginal design
      of coping.
AB  - STATEMENT OF PROBLEM: The opaque color of zirconia copings may compromise
      esthetics, especially in the facial cervical area. A collarless zirconia coping
      can be an alternative. However, the strength of zirconia crowns with collarless
      copings is unknown. PURPOSE: The purpose of this study was to compare the
      fracture load of zirconia crowns according to coping thickness and facial collar
      design. MATERIAL AND METHODS: Forty-eight zirconia crowns were fabricated and
      divided into 4 groups: standard coping group (0.5 mm coping thickness, 0.2 mm
      facial collar height); collarless coping group (0.5 mm coping thickness, no
      facial collar); modified thicker coping group (0.7 mm coping thickness, 0.2 mm
      facial collar height); and thicker coping group (0.7 mm coping thickness
      including collar height). The fracture load for the crowns was measured in a
      universal testing machine. One-way ANOVA and the Tukey HSD test for post hoc
      analysis were used for statistical analysis (alpha=.05). Ten additional zirconia
      crowns were fabricated to test the effect of cyclic loading on fracture
      resistance between the standard coping group and the collarless coping group, and
      data were analyzed with the Mann-Whitney U test. RESULTS: The fracture load in
      the collarless coping group (2329.1 N+/-948.3) was not significantly different
      from that of the other groups. The thicker coping group (3179.3 N+/-1137.7)
      resulted in significantly greater fracture load than the standard (2126.9 N+/
      576.9) and modified thicker coping groups (2112.7 N+/-623.9) (F=4.193; P=.011).
      The fracture load after cyclic loading did not differ significantly between the
      standard coping group and the collarless coping group. CONCLUSIONS: Within the
      limitations of this in vitro study, the thicker coping group had the highest
      fracture strength, but the collarless coping group using a 0.5 mm thickness
      coping was not significantly different from the standard coping group.

PMID- 22867807
TI  - Surface detail reproduction under simulated pulpal pressure: a 3-dimensional
      optical profilometer and scanning electron microscopy evaluation.
AB  - STATEMENT OF PROBLEM: It is not clear whether more hydrophilic impression
      materials are better able to copy and transfer dentin surface detail than less
      hydrophilic ones. PURPOSE: The purpose of this study was to evaluate the
      reproduction of dentin surface detail by means of hydrophobic and hydrophilic
      elastomeric impression materials under simulated pulpal pressure and their
      ability to transfer surface detail onto casts produced from such impressions.
      MATERIAL AND METHODS: The wettability of the impression materials (n=8) was
      determined by contact angle measurement with an evolution period of 135 seconds.
      Dentin moisture was provided by means of pulpal pressure simulation, and
      objective analyses were performed by measuring the average roughness value (Ra)
      with a 3-D optical profilometer (n=10). One specimen from each group was analyzed
      with scanning electron microscopy. Contact-angle values were analyzed with a
      repeated measures ANOVA, and detail reproduction was tested with 3-way ANOVA
      (alpha=.05). The Bonferroni correction was used to control Type I error for
      follow-up analyses. RESULTS: Contact angle measurements revealed significant
      differences depending on the impression material used and time of the measurement
      (P<.001). The Ra values of the hydrophilic impression materials, which were made
      from dry specimens, and the pulpal pressure simulated dentin surfaces did not
      differ from the dentin surfaces (P>.013). The hydrophobic impression material
      showed similar detail reproduction ability in a dry field, but loss of detail
      (evaluated subjectively) and increased roughness values (evaluated objectively)
      were recorded in a moisturized field (P=.004). Polyurethane-based cast material
      successfully reproduced the surface texture (P>=.006), whereas Type IV gypsum
      material was unable to reproduce this texture to the same extent. CONCLUSIONS:
      The hydrophilic impression materials tested showed similar ability to reproduce
      detail under simulated pulpal pressure. Polyurethane-based cast material
      successfully reproduced the surface texture.

PMID- 22867808
TI  - Dimensional stability of contemporary irreversible hydrocolloids: humidor versus
      wet tissue storage.
AB  - STATEMENT OF PROBLEM: The storage time and conditions of irreversible
      hydrocolloid impressions affect their accuracy and in turn the precision of the
      definitive cast. Recommendations for proper storage are, however, based on
      theoretical assumptions rather than facts. PURPOSE: The purpose of this study was
      to assess the influence of the 2 most common storage conditions on the
      dimensional stability of 7 contemporary irreversible hydrocolloids (IH) for a
      period of up to 7 days. MATERIAL AND METHODS: Twelve specimens per material
      (Blueprint, Cavex CA37, Cavex ColorChange, Jeltrate, Orthoprint, Cavex
      Orthotrace, and Tetrachrom) were fabricated according to ISO/CD 21563. The
      specimens were either stored in a humidor (n=6) or wrapped in a wet tissue (n=6)
      inside a plastic bag (bag/tissue). The linear dimensional change of the specimens
      was calculated (Delta| [%]) at baseline and after a storage time of 1, 2, 4, 24,
      48, 72, 120, and 168 hours. Data were subjected to a repeated measures ANOVA,
      followed by post hoc comparisons (Tukey HSD Test, Games-Howell Test) at
      alpha=.05. RESULTS: For specimens stored in the humidor, Delta| ranged from 0.33%
      to -2.35% and in the bag/tissue from 2.89% to -2.8%. Storage in the bag/tissue
      resulted in the most unpredictable results. The color-changing IH showed a
      pronounced expansion when stored in the bag/tissue. CONCLUSIONS: If humidor
      storage is used, IH impressions should be poured within 4 hours. If bag/tissue
      storage is used, noncolor-change IH impressions should, preferably, be poured
      within 2 hours. In general, the color-change IHs studied had higher dimensional
      change values. For optimum dimensional stability, IH impressions should be poured
      as soon as possible.

PMID- 22867809
TI  - The prosthetic rehabilitation of a panfacial fracture patient after reduction: a
      clinical report.
AB  - Panfacial fractures involve trauma to the lower, middle, and upper facial bones
      and often require a team approach for management. Early and complete restoration
      of preinjury facial contours and function should be the goal of the oral and
      maxillofacial surgeon and the prosthodontist. When the intraoral landmarks are
      lost, overall facial anatomic landmarks can be used to restore the oral cavity. A
      patient with complex clinical panfacial fractures, including a vertically and
      horizontally malpositioned native alveolar bone and severe facial asymmetry, is
      presented. A functional and esthetic rehabilitation was successfully accomplished
      by using a partial removable dental prosthesis retained with telescopic crowns
      and magnetic attachments in the maxilla and osseointegrated implants to support a
      definitive dental prosthesis in the mandible.

PMID- 22867810
TI  - Silicone nasal prosthesis retained by an intranasal stent: a clinical report.
AB  - Nasal defects after tumor excision can leave a patient functionally and
      esthetically impaired. Loss of nasal septal cartilage support causes the soft
      tissue to collapse or undergo stenosis, further compounding the problem.
      Intranasal stents can be used to maintain the patency of such nasal defects. This
      clinical report describes the use of an acrylic resin nasal stent bonded to a
      silicone nasal prosthesis to rehabilitate a patient with a nasal defect.

PMID- 22867811
TI  - Modification of a smooth staple implant abutment.

PMID- 22867812
TI  - 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) decreases progesterone synthesis
      through cAMP-PKA pathway and P450scc downregulation in mouse Leydig tumor cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in
      textiles, plastics and electronics and represent a group of persistent
      environmental contaminants. They have been found to accumulate in human and
      marine mammals. Previous studies have shown that PBDEs have endocrine-disrupting
      properties and reproductive toxicity. However, the mechanisms under the
      reproductive disruptions are still not well understood. In this study, we
      explored the effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on
      progesterone biosynthesis and possible mechanisms in mouse Leydig tumor cells
      (mLTC-1). Our results showed that BDE-47 could reduce progesterone production and
      decrease the intracellular cAMP level induced by hCG or forskolin. These
      suggested that BDE-47 decreasing progesterone production in mLTC-1 cells may be
      associated with the decline of intracellular cAMP level. Moreover, our data also
      indicated that the site G protein in cAMP-PKA pathway may be involved in this
      process. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse
      the decrease of progesterone biosynthesis, indicating that a post-cAMP site (or
      sites) might be involved into the BDE-47-decreased progesterone production. In
      addition, we found BDE-47 reduced the activity of P450 side chain cleavage enzyme
      (P450scc), which was companied with the decline of P450scc mRNA and protein level
      in mLTC-1 cells. Put all together, these results suggested that progesterone
      synthesis decrease induced by BDE-47 may be associated with attenuation of cAMP
      generation and reduction of P450scc activity.

PMID- 22867813
TI  - Coping motives, negative moods, and time-to-drink: exploring alternative analytic
      models of coping motives as a moderator of daily mood-drinking covariation.
AB  - Affect regulation models of alcohol use posit individuals use alcohol to modify
      mood states. Importantly, these models hypothesize that individual differences in
      coping motives for drinking moderate the relation between drinking and negative
      moods. Despite consistently significant correlations among negative moods, coping
      motives, and alcohol involvement in numerous between-level studies, within-person
      analyses have yielded results inconsistent with theoretical models. Analytic
      techniques modeling time-to-drink have provided results more consistent with
      theory, though there remains a paucity of research using these methods. The
      purpose of the current study was to explore whether coping motives moderate the
      relation between negative moods and the immediacy of drinking using methodology
      outlined by Hussong (2007) and Armeli, Todd, Conner, and Tennen (2008). Overall,
      our study showed little evidence for hypothesized mood-motive-alcohol use
      relations, thus demonstrating that time-to-drink approaches may not provide more
      consistent support for these hypotheses.

PMID- 22867814
TI  - Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is a curable malignancy which shows a bimodal curve in
      incidence in economically developed countries; there is a putative association
      with Epstein-Barr virus. The WHO 2008 classification schema recognises two
      histological types of HL: the nodular lymphocyte predominant and the "classic"
      HL. The latter encompasses four entities: nodular sclerosis, mixed cellularity,
      lymphocyte depletion, and lymphocyte-rich. Most patients with HL present with
      asymptomatic superficial lymphadenopathy. The commonest sites of disease are the
      cervical, supraclavicular and mediastinal lymph nodes, while sub-diaphragmatic
      presentations and bone marrow and hepatic involvement are less common. Splenic
      involvement is usually concomitant with hepatic disease and systemic symptoms;
      extranodal presentations are quite rare. Systemic symptoms are present in ~35% of
      cases. The stage of disease is defined according to the Ann Arbor staging system
      or its Cotswolds variant, and staging work-up includes physical examination,
      chest X-rays, chest and abdominal CT scan, and bone marrow biopsy. (18)FDG-PET
      ((18)fluordeoxyglucose positron emission tomography) plays a central role in
      staging, response assessment and prognosis definition. Classic HL usually spreads
      by contiguity within the lymphatic tissue network, with a late extension to
      adjacent and distant viscera. Mortality from HL has been progressively
      decreasing, as confirmed by the most recent 5-year survival figure of 81%. The
      list of putative prognostic factors in HL has been increasing, but most factors
      still require prospective validation. Some of these variables are used to
      stratify early-stage disease into "favourable" and "unfavourable" categories,
      with "unfavourable early-stage" being intermediate between "favourable early
      stage" and "advanced-stage". ABVD (adriamycin(doxorubicin), bleomycin,
      vinblastine, dacarbazine) combination chemotherapy followed by involved-field
      irradiation is the standard treatment for patients with early-stage HL, with a 5
      year OS >95%. Several trials assessing less intensive approaches for patients
      with favourable early-stage HL are ongoing. More intensified combinations, such
      as the BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine
      (Oncovin), procarbazine, prednisone) regimen, are being investigated, usually in
      patients with unfavourable early-stage HL and interim PET+. ABVD is the standard
      chemotherapy treatment also for patients with advanced disease. Although some
      evidence suggests that more intensive combinations provide better disease
      control, the inevitable increased risk of relevant late toxicity worries
      investigators. Consequently, there has been a shift towards investigating the
      innovative strategy of a more aggressive schedule for patients with (18)FDG-PET
      positive results after the first 2 courses of ABVD. High-dose chemotherapy
      supported by ASCT (autologous stem cell transplantation) is considered the
      standard of care in patients with HL which has relapsed after, or is refractory
      to conventional chemoradiotherapy, while allogeneic transplant is a suitable tool
      for patients with chemorefractory disease and patients failed after ASCT.

PMID- 22867815
TI  - Isolated sternal fractures treated on an outpatient basis.
AB  - AIM: The aim of this study is to investigate the need for admission of patients
      with isolated sternal fracture (ISF) by prospectively and randomly discharging or
      admitting them. METHODS: Patients with ISF after the completion of investigations
      were randomly discharged or admitted. Investigations performed included lateral
      chest x-ray; chest computed tomography; electrocardiogram; cardiac ultrasound;
      definition of C-reactive protein; and cardiac enzymes, such as creatine
      phosphokinase, myocardial branch of creatine phosphokinase, and troponin I
      (cardiac specific). These investigations were repeated after 6 hours in the
      admission and the next day in both groups. RESULTS: Forty-two patients were
      included in the study. Twenty-one were admitted, whereas 21 were discharged.
      Electrocardiogram and ultrasound were normal in both groups upon presentation and
      the next day. Creatine phosphokinase and myocardial branch of creatine
      phosphokinase, although elevated at presentation, were normal the next day and
      similar in both groups. There was no morbidity, need for surgery, or mortality in
      both groups during a 6-month follow-up. CONCLUSIONS: Patients with ISF can be
      discharged safely as soon as investigations are completed. Extensive myocardial
      assessment is not needed on the posttraumatic period. Myocardial involvement
      seems unlikely in patients with ISF, who can be treated with oral analgesics.

PMID- 22867817
TI  - Comparison of pulse carbon monoxide oximetry with laboratory carbon monoxide
      oximetry regarding the time to diagnosis and treatment of patients with carbon
      monoxide poisoning: is it a reasonable and necessary comparison?

PMID- 22867818
TI  - Monomorphic ventricular tachycardia after intentional citalopram overdose.

PMID- 22867819
TI  - Brain computed tomographic scan findings in acute opium overdose patients.
AB  - AIM: Early radiologic evaluations including noncontrast computed tomographic (CT)
      scan of the brain have been reported to be useful in the diagnosis and management
      of the intoxicated patients. Changes in the brain CT scan of the acute opium
      overdose patients have little been studied to date. This study aimed to evaluate
      changes of the brain CT scans in the acute opium overdose patients. METHODS: In
      this retrospective study, medical records of all acute opium overdose patients
      hospitalized in Loghman-Hakim Poison Hospital in Tehran, Iran, between September
      2009 and September 2010 were identified. Those who had undergone noncontrast
      brain CT within the first 24 hours of hospital presentation were included.
      Patients with any underlying disease, head trauma, underlying central nervous
      system disease, epilepsy, and multidrug ingestion were excluded. The patients'
      demographic information, vital signs, and laboratory data at presentation were
      extracted and recorded. The data were analyzed using SPSS software version 17
      (SPSS, Chicago, IL). RESULTS: A total of 71 patients were included. Fifty-eight
      patients (80.5%) survived, and 10 (13.8%) died. Fourteen cases (19.7%) had
      abnormal CT findings including 8 cases of generalized cerebral edema and 6 cases
      of infarction/ischemia. There were no statistically significant differences
      between the patients with and without abnormal CT scan findings with respect to
      age, sex, systolic and/or diastolic blood pressures, pulse rate, respiratory
      rate, occurrence of seizures, pH, Pco(2), HCO(3)(-), blood sodium level, and
      blood glucose level (all P values were > .05). However, a statistically
      significant difference was found between these patients in terms of outcome (P =
      .007). CONCLUSION: Abnormal brain CT findings are detected in about 20% of the
      acute opium overdose patients who are ill enough to warrant performance of the
      brain CT scan and associate with a poor prognosis in this group of the patients.

PMID- 22867820
TI  - End-tidal carbon dioxide is associated with mortality and lactate in patients
      with suspected sepsis.
AB  - OBJECTIVE: Exhaled end-tidal carbon dioxide (ETCO(2)) concentration is associated
      with lactate levels in febrile patients. We assessed the association of ETCO(2)
      with mortality and lactate levels in patients with suspected sepsis. METHODS:
      This was a prospective observational study. We enrolled 201 adult patients
      presenting with suspected infection and 2 or more systemic inflammatory response
      syndrome criteria. Lactate and ETCO(2) were measured and analyzed with patient
      outcomes. RESULTS: The area under the receiver operator characteristics curve
      (AUC) was 0.75 (confidence interval [CI], 0.65-0.86) for lactate and mortality
      and 0.73 (CI, 0.61-0.84) for ETCO(2) and mortality. When analyzed across the
      different categories of sepsis, the AUCs for lactate and mortality were 0.61 (CI,
      0.36-0.87) for sepsis, 0.69 (CI, 0.48-0.89) for severe sepsis, and 0.74 (CI, 0.55
      0.93) for septic shock. The AUCs for ETCO(2) and mortality were 0.60 (CI, 0.37
      0.83) for sepsis, 0.67 (CI, 0.46-0.88) for severe sepsis, and 0.78 (CI, 0.59
      0.96) for septic shock. There was a significant inverse relationship between
      ETCO(2) and lactate in all categories, with correlation coefficients of -0.421 (P
      < .001) in the sepsis group, -0.597 (P < .001) in the severe sepsis group, and 
      0.482 (P = .011), respectively. Adjusted odds ratios were calculated,
      demonstrating 3 significant predictors of mortality: use of vasopressors 16.4
      (95% CI, 1.80-149.2), mechanical ventilation 16.4 (95% CI, 3.13-85.9), and
      abnormal ETCO(2) levels 6.48 (95% CI, 1.06-39.54). CONCLUSIONS: We observed a
      significant association between ETCO(2) concentration and in-hospital mortality
      in emergency department patients with suspected sepsis across a range of disease
      severity.

PMID- 22867821
TI  - Minor head injury in the elderly at very low risk: a retrospective study of 6
      years in an Emergency Department (ED).
AB  - INTRODUCTION: Mild head injury (MHI) is a common clinical problem in emergency
      departments (EDs). Long-standing debate is still going on about MHI in the
      elderly: current guidelines recommend to perform a CT scan on this group.
      MATERIALS AND METHODS: We performed a retrospective study by reviewing patients
      older than 65 years, evaluated in our ED for which a CT scan of the head was
      performed for MHI, between 2004 and 2010. According to Italian Guidelines, we
      considered only patients with low-risk MHI. RESULTS: We considered 2149 eligible
      patients: we recorded 47 pathological acute findings on CT scan (2.18%), but only
      3 patients (0.14%) underwent neurosurgery. We analysed our patients according to
      different age groups: in patients in the 65- to 79-year-old group, we documented
      pathological findings on CT in 0.66% of cases, with a significant increase in the
      group older than 80 years, with a rate of 3.33% of acute findings on CT (OR 5.22,
      P < .001); 617 patients were on antiplatelet therapy: 22 of these patients
      (3.72%) had a pathological finding on CT scan (OR 2.23, P < .005). DISCUSSION:
      Our retrospective analyses demonstrated that the incidence of intracranial
      complications after MHI is not different from that of the general population, and
      based on this finding, a CT does not seem to be necessary, at least up to 80
      years old. Our data suggest that antiplatelet therapy could be a significant risk
      factor. Our results suggest that elderly patients between 65 and 79 years old
      without risk factors could be managed as younger patients.

PMID- 22867822
TI  - Gastric perforation after cardiopulmonary resuscitation.
AB  - Gastric rupture is a rare complication after cardiopulmonary resuscitation (CPR).
      In most cases, incorrect management of airways during CPR is the main cause.
      Therefore, a medical emergency becomes a surgical emergency also. We present a
      case of gastric perforation in a middle-aged patient after CPR performed by his
      family. He eventually presented with bloody vomitus and a tympanic abdomen. When
      faced with a patient with abdominal signs post-CPR, surgical complications of CPR
      should be considered.

PMID- 22867823
TI  - A new technique for evaluating jugular venous distension in congestive heart
      failure using ultrasound.

PMID- 22867824
TI  - Red cell distribution width as a prognostic marker in patients with community
      acquired pneumonia.
AB  - BACKGROUND: Red cell distribution width (RDW) is associated with mortality in
      both the general population and in patients with certain diseases. However, the
      relationship between RDW and mortality in patients with community-acquired
      pneumonia (CAP) is unknown. The objective of this study was to evaluate the
      association of RDW with mortality in patients with CAP. METHODS: We performed a
      retrospective analysis of a prospective registry database of patients with CAP.
      Red cell distribution width was organized into quartiles. The pneumonia severity
      index (PSI) and CURB-65 were calculated. The primary outcome was 30-day
      mortality. Secondary outcomes included the length of hospital stay, admission to
      the intensive care unit, vasopressor use, and the need for mechanical
      ventilation. RESULTS: A total of 744 patients were included. The PSI and CURB-65
      were higher in patients with a high RDW. Multivariate logistic regression
      analysis identified higher categories of RDW, PSI, CURB-65, and albumin as
      statistically significant variables. Thirty-day mortality was significantly
      higher in patients with a higher RDW. Among the secondary outcomes, the length of
      hospital stay and vasopressor use were significantly different between the
      groups. In a Cox proportional hazard regression analysis, patients with higher
      categories of RDW exhibited increased mortality before and after adjustment of
      the severity scales. Receiver operating characteristics curves demonstrated
      improved mortality prediction when RDW was added to the PSI or CURB-65.
      CONCLUSION: Red cell distribution width was associated with 30-day mortality,
      length of hospital stay, and use of vasopressors in hospitalized patients with
      CAP. The inclusion of RDW improved the prognostic performance of the PSI and CURB
      65.

PMID- 22867825
TI  - External contention for pelvic trauma: is 1 sheet enough?

PMID- 22867827
TI  - Do energy drinks cause epileptic seizure and ischemic stroke?
AB  - Energy drinks are popular among young individuals and marketed to college
      students, athletes, and active individuals between the ages of 21 and 35 years.
      We report a case that had ischemic stroke and epileptic seizure after intake of
      energy drink with alcohol. To the best of our knowledge, the following case is
      the first report of ischemic stroke after intake of energy drink. A previously
      healthy 37-year-old man was brought to the emergency department after a witnessed
      tonic-clonic seizure. According to his wife's testimony, just before loss of
      consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull,
      Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a
      history of seizures, head trauma, or family history of seizures or another
      disease. In cranial diffusion magnetic resonance imaging, there were hyperintense
      signal changes in bilateral occipital area (more pronounced in the left occipital
      lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests
      associated with possible etiologic causes of ischemic stroke in young patients
      were negative. Herein, we want to attract attention to adverse effect of energy
      drink usage.

PMID- 22867828
TI  - Do outcomes of near syncope parallel syncope?

PMID- 22867826
TI  - Therapeutic use of omega-3 fatty acids in severe head trauma.
AB  - Traumatic brain injury (TBI) has long been recognized as the leading cause of
      traumatic death and disability. Tremendous advances in surgical and intensive
      care unit management of the primary injury, including maintaining adequate
      oxygenation, controlling intracranial pressure, and ensuring proper cerebral
      perfusion pressure, have resulted in reduced mortality. However, the secondary
      injury phase of TBI is a prolonged pathogenic process characterized by
      neuroinflammation, excitatory amino acids, free radicals, and ion imbalance.
      There are no approved therapies to directly address these underlying processes.
      Here, we present a case that was intentionally treated with substantial amounts
      of omega-3 fatty acids (n-3FA) to provide the nutritional foundation for the
      brain to begin the healing process following severe TBI. Recent animal research
      supports the use of n-3FA, and clinical experience suggests that benefits may be
      possible from substantially and aggressively adding n-3FA to optimize the
      nutritional foundation of severe TBI patients and must be in place if the brain
      is to be given the opportunity to repair itself to the best possible extent.
      Administration early in the course of treatment, in the emergency department or
      sooner, has the potential to improve outcomes from this potentially devastating
      public health problem.

PMID- 22867829
TI  - Two cases of disseminated intravascular coagulation due to "bath salts" resulting
      in fatalities, with laboratory confirmation.

PMID- 22867830
TI  - Improving cardiac function with new-generation plasma volume expanders.
AB  - BACKGROUND: Plasma expander (PE) based on polyethylene glycol (PEG) conjugated to
      albumin has shown positive results maintaining blood volume during hemodilution
      and restoring blood volume during resuscitation from hemorrhagic shock.
      Polyethylene glycol conjugation to human serum albumin (HSA), PEG-HSA, increases
      size, weight, and colloidal osmotic pressure, with minor effects on solution
      viscosity. METHODS: This study was designed to test the hypothesis that PEG-HSA
      (2 g/dL) produced by direct PEGylation chemistry improves cardiac function during
      2 experimental models, (i) moderate hemodilution and (ii) resuscitation from
      hemorrhagic shock, compared with a conventional colloidal PE (Dextran 70 kd
      [Dx70], 6 g/dL). Cardiac function was studied using a miniaturized pressure
      volume conductance catheter implanted in the left ventricle and evaluated in
      terms of cardiac indices derived from the pressure volume measurements. RESULTS:
      Polyethylene glycol-HSA increased cardiac output, stroke volume, and stroke work
      and decreased systemic vascular resistance compared with Dx70 in both
      experimental models. The improvements induced by PEG-HSA in cardiac function were
      sustained over the observation time. Polyethylene glycol-HSA cardiac
      mechanoenergetics changes are the result of increased energy transferred per
      stroke and decreased resistance of the vasculature connecting the heart. In
      summary, PEG-HSA decreased left ventricle ejection impedance. CONCLUSION:
      Ejection of blood diluted with PEG-HSA presented a reduced load to the heart,
      increased contractile function, and lowered the energy consumed per unit volume
      compared with Dx70. Our results emphasize the importance of heart function as a
      parameter to be included in the evaluation changes induced by new PEs.

PMID- 22867831
TI  - Fatality in a patient treated with dabigatran.

PMID- 22867832
TI  - Apoptosis is involved in the mechanism of postresuscitation myocardial
      dysfunction in a porcine model of cardiac arrest.
AB  - BACKGROUND: Postresuscitation myocardial dysfunction contributes to the low
      survival rate after successful resuscitation, but its mechanism remains poorly
      understood. This study investigated whether caspase 3-mediated apoptosis is
      activated in the heart after postresuscitation myocardial dysfunction. METHODS:
      After pigs were subjected to 8 minutes of electrically induced cardiac arrest
      (CA), standard cardiopulmonary resuscitation was performed. Animals in the post
      return of spontaneous circulation (ROSC) group were randomly assigned to be
      killed (n = 6 per group) at 12 and 24 hours after ROSC, and myocardial specimens
      were analyzed with electron microscopy, Western blotting, quantitative real-time
      polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling assay. RESULTS: Myocardial function was significantly
      impaired after ROSC. Expression of Bcl-2, Bax, and caspase 3 protein was markedly
      increased in the post-ROSC group compared with the sham-operated group (P < .05)
      at 12 and 24 hours after ROSC, whereas Bcl-2/Bax was significantly reduced in the
      post-ROSC group compared with the sham-operated group (P < .05). The messenger
      RNA levels of caspase 3 were significantly elevated at 12 and 24 hours after
      ROSC, and increases in caspase 3 activity indicated activation of the
      mitochondrial apoptotic pathway. Typical apoptotic nuclei were observed in
      cardiomyocytes 24 hours after ROSC. More apoptotic cells were observed in animals
      that had undergone CA compared with sham-operated animals (P < .05). CONCLUSION:
      Caspase 3-mediated apoptosis may be one of the main pathologic mechanisms of
      postresuscitation myocardial injury in a porcine model of CA.

PMID- 22867833
TI  - Gastric pneumatosis secondary to celiac axis occlusion: an unusual cause of
      abdominal pain.

PMID- 22867834
TI  - The value of prehospital echocardiography in shock management.

PMID- 22867835
TI  - Systemic thrombolysis for stroke in pregnancy.

PMID- 22867836
TI  - Randomized trials in emergency medicine journals, 2008 to 2011.
AB  - STUDY OBJECTIVE: Knowledge of current areas of activity in emergency medicine
      research may improve collaboration among investigators and may help inform
      decisions about future research priorities. Randomized, controlled trials are a
      key component of research activity and an essential tool for improving care. We
      investigated the characteristics of randomized trials recently published in
      emergency medicine journals. METHODS: This was a retrospective analysis of
      randomized trials published in the 5 highest impact emergency medicine journals.
      PubMed was searched for reports of randomized trials involving human subjects
      indexed to MEDLINE between January 1, 2008, and December 31, 2011. Included
      trials were classified with respect to study topic, funding source, presence of
      age-related inclusion criteria, and country of origin. RESULTS: A total of 163
      published studies were included for analysis. Pain management was the most
      commonly studied topic (n = 28, or 17%) followed by orthopedics (n = 24, or 15%),
      cardiovascular disease (n = 13, or 8%), and prehospital medicine (n = 13, or 8%).
      Less than half of studies received extramural funding support. Children were
      specifically examined in 22 (13%) of trials; only 5 trials (3%) specifically
      examined patients aged 60 or older. CONCLUSIONS: Emergency medicine journals
      publish randomized trials addressing a wide range of clinical topics. Randomized
      trials focusing on geriatric patients are not commonly published in these
      journals.

PMID- 22867837
TI  - Unnecessary surgery for acute abdomen secondary to angiotensin-converting enzyme
      inhibitor use.
AB  - Acute abdominal pain is the reason for 5% to 10% of all emergency department
      visits. In 1 in every 9 patients, operated on for an acute abdomen, laparotomy is
      negative. In a minority of patients, the acute abdomen is caused by side effects
      of medication. We present a case of unnecessary abdominal surgery in a patient
      with acute abdominal pain caused by intestinal angioedema (AE), which was
      eventually due to angiotensin-converting enzyme inhibitor (ACE-i) use. We hope
      that this case report increases awareness of this underdiagnosed side effect.
      Emergency department physicians, surgeons, internists, and family physicians
      should always consider ACE-i in the differential diagnosis of unexplained
      abdominal pain. Since early withdrawal of the medication causing intestinal AE
      can prevent further complications and, in some cases, needless surgery, we
      propose an altered version of the known diagnostic algorithm, in which ACE-i and
      nonsteroidal anti-inflammatory drugs-induced AE is excluded at an early stage.

PMID- 22867838
TI  - Optimal external laryngeal manipulation: modified bimanual laryngoscopy.
AB  - OBJECTIVES: External laryngeal manipulation (ELM) is commonly used to facilitate
      laryngeal view during direct laryngoscopy. We evaluated the effectiveness of the
      newly modified bimanual laryngoscopy, which involves a direct guidance of an
      assistant's hand by a laryngoscopist, to optimize laryngeal exposure during
      direct laryngoscopy compared with conventional bimanual laryngoscopy. METHODS: A
      total of 78 adult patients were included. Patients were randomly allocated to 1
      of 2 groups: group C (ELM using conventional bimanual laryngoscopy) or group M
      (ELM using the modified bimanual laryngoscopy). The difference in percentage of
      glottic opening scores after the application of ELM, the number of ELM attempts,
      and the time taken to obtain the best laryngeal view during ELM were recorded.
      RESULTS: The differences in the percentage of glottic opening score before and
      after the initial attempt of ELM significantly improved in group M compared with
      group C (40% [30%-50%] vs 30% [15%-35%], median [interquartile range],
      respectively; P < .001). The success rate of achieving the best laryngeal view on
      the first attempt was higher in group M than in group C (87% vs 36%,
      respectively; P < .001). The time taken for obtaining the best laryngeal view
      after the first ELM attempt was significantly shorter in group M than in group C
      (3 [3-4] vs 7 [4-8] seconds, median [interquartile range], respectively; P <
      .001). CONCLUSION: The modified bimanual laryngoscopy is more effective for
      obtaining the optimal laryngeal view on the first attempt compared with the
      conventional bimanual laryngoscopy.

PMID- 22867839
TI  - Simultaneous determination and pharmacokinetic study of six flavonoids from
      Fructus Sophorae extract in rat plasma by LC-MS/MS.
AB  - In this study, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been developed and validated for the determination of six flavonoids
      including sophoricoside, genistin, genistein, rutin, quercetin and kaempferol in
      rat plasma after oral administration of Fructus Sophorae extract using
      sulfamethalazole as internal standard (IS). The plasma samples were pretreated
      and extracted by liquid-liquid extraction. Chromatographic separation was
      accomplished on a C(18) column with a simple linear gradient elution. The
      detection was accomplished by multiple-reaction monitoring (MRM) scanning after
      electrospray ionization (ESI) source operating in the negative ionization mode.
      The optimized mass transition ion pairs (m/z) for quantitation were 431.1/267.9
      for sophoricoside and genistin, 269.0/133.0 for genistein, 609.2/300.0 for rutin,
      301.0/150.9 for quercetin, 284.9/93.0 for kaempferol and 252.0/155.9 for IS. The
      total run time was 8.0 min. Full validation of the assay was implemented
      including specificity, linearity, accuracy, precision, recovery and matrix
      effect. This is the first report on determination of the major flavones in rat
      plasma after oral administration of Fructus Sophorae extract. The results
      provided a meaningful basis for the clinical application of this herb.

PMID- 22867840
TI  - Quantification of acetaminophen and two of its metabolites in human plasma by
      ultra-high performance liquid chromatography-low and high resolution tandem mass
      spectrometry.
AB  - The quantification of acetaminophen (APAP) and two of its metabolites, i.e.
      acetaminophen-glucuronide (APAP-GLUC) and acetaminophen-cysteine (APAP-CYS), is
      described in human plasma using ultra-high performance liquid chromatography
      coupled to a triple quadrupole linear ion trap mass spectrometer operating in the
      selected reaction monitoring (SRM/MS) mode and to a high resolution quadrupole
      time-of -flight mass spectrometer operating in the MS/MS (HR-SRM/MS) mode.
      Starting with a 50 MUL plasma aliquot, a generic sample preparation was performed
      using protein precipitation with methanol/ethanol. Both methods were found to be
      linear over 2.5 orders of magnitude. Similar performances to the SRM/MS assay
      were obtained for APAP, APAP-CYS and APAP-GLUC using high resolution-selected
      reaction monitoring mode with LLOQ of 20, 50 and 50 ng/mL, respectively. For all
      analytes, precision was found to be better than 12% and accuracy in the range
      90.3-109%. The present study demonstrates the ability of QqTOF platforms for
      accurate and precise quantification in MS/MS mode using short duty cycle with
      similar sensitivity to LC-SRM/MS. Additionally, as full scan data MS(ALL) are
      available qualitative and quantitative information on metabolites can also be
      obtained in a single LC-MS run.

PMID- 22867841
TI  - Development of a gas chromatographic method for the determination of Chlorpyrifos
      and its metabolite Chlorpyrifos-oxon in wine matrix.
AB  - A reliable method has been developed for the determination of Chlorpyrifos (CP)
      and its metabolite Chlorpyrifos-oxon (CPO) in wine sample using pulsed splitless
      technique coupled with gas chromatography by using electron capture detector. In
      this study, a quick, easy and cheap sample preparation method (QuEChERS) based on
      liquid extraction with acetonitrile, followed by dispersive solid phase
      extraction using primary secondary amine was tested for the separation and
      quantification of CP and CPO in wine samples. The accuracy of the developed
      method was tested upon recovery studies and it was calculated as (92.3 +/- 18.2)%
      for CP and (96.6 +/- 16.1)% for CPO. LOD and LOQ values of CP were found as 0.04
      and 0.15 ng/mL and 0.49 and 1.62 ng/mL for CPO respectively. By using the pulsed
      splitless injection mode, the sensitivity of the determination of CP and its
      metabolite CPO in wine samples was improved compared to splitless technique. CP
      content of analyzed wine sample was found as 2.05 +/- 0.15 ng/mL with a RSD of
      7.6% and CPO content was found as 4.99 +/- 0.15 ng/mL with a RSD of 3.0% (n=3).
      The expanded measurement uncertainties were calculated as 17% and 6% for CP and
      CPO, respectively.

PMID- 22867842
TI  - Effect of background correction on peak detection and quantification in online
      comprehensive two-dimensional liquid chromatography using diode array detection.
AB  - A singular value decomposition-based background correction (SVD-BC) technique is
      proposed for the reduction of background contributions in online comprehensive
      two-dimensional liquid chromatography (LC*LC) data. The SVD-BC technique was
      compared to simply subtracting a blank chromatogram from a sample chromatogram
      and to a previously reported background correction technique for one dimensional
      chromatography, which uses an asymmetric weighted least squares (AWLS) approach.
      AWLS was the only background correction technique to completely remove the
      background artifacts from the samples as evaluated by visual inspection. However,
      the SVD-BC technique greatly reduced or eliminated the background artifacts as
      well and preserved the peak intensity better than AWLS. The loss in peak
      intensity by AWLS resulted in lower peak counts at the detection thresholds
      established using standards samples. However, the SVD-BC technique was found to
      introduce noise which led to detection of false peaks at the lower detection
      thresholds. As a result, the AWLS technique gave more precise peak counts than
      the SVD-BC technique, particularly at the lower detection thresholds. While the
      AWLS technique resulted in more consistent percent residual standard deviation
      values, a statistical improvement in peak quantification after background
      correction was not found regardless of the background correction technique used.

PMID- 22867843
TI  - Multi-residue determination of pharmaceutical and personal care products in
      vegetables.
AB  - Treated wastewater irrigation and biosolid amendment are increasingly practiced
      worldwide and contamination of plants, especially produces that may be consumed
      raw by humans, by pharmaceutical and personal care products (PPCPs), is an
      emerging concern. A sensitive method was developed for the simultaneous
      measurement of 19 frequently-occurring PPCPs in vegetables using high-performance
      liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI
      MS/MS) for detection, combined with ultrasonic extraction and solid phase
      extraction (SPE) cleanup for sample preparation. Deuterated standards were used
      as surrogates to quantify corresponding analytes. The corrected recoveries ranged
      between 87.1 and 123.5% for iceberg lettuce, with intra- and inter-day variations
      less than 20%, and the method detection limits (MDLs) in the range of 0.04-3.0 ng
      g-1 dry weight (dw). The corrected recoveries were equally good when the method
      was used on celery, tomato, carrot, broccoli, bell pepper and spinach. The method
      was further applied to examine uptake of PPCPs by iceberg lettuce and spinach
      grown in hydroponic solutions containing each PPCP at 500 ng L-1. Twelve PPCPs
      were detected in lettuce leaves with concentrations from 0.2 to 28.7 ng g-1 dw,
      while 11 PPCPs were detected in spinach leaves at 0.04-34.0 ng g-1 dw. Given the
      diverse chemical structures of PPCPs considered in this study, this method may be
      used for screening PPCP residues in vegetables and other plants impacted by
      treated wastewater or biosolids, and to estimate potential human exposure via
      dietary uptake.

PMID- 22867845
TI  - [XXXVIII National Congress of the SEEIUC].

PMID- 22867844
TI  - Evaluation of anti-norovirus IgY from egg yolk of chickens immunized with
      norovirus P particles.
AB  - Noroviruses (NoVs) are a leading cause of epidemic acute gastroenteritis
      affecting millions of people worldwide. Understanding of NoV remains limited due
      to the lack of a cell culture system and small animal models. Currently, there
      are no effective vaccines or antivirals against NoVs. In this study, an approach
      for large-scale production of anti-NoV antibodies for use as a potential
      treatment for NoV disease using passive immunization was evaluated. NoV-specific
      immunoglobulins (IgYs) were produced by immunizing chickens with NoV P particles.
      The birds continuously produced high titers of antibodies in their eggs for at
      least 3months, in which NoV-specific antibody levels reached 4.7-9.2mg/egg yolk.
      The egg yolk antibodies strongly reacted with NoV P particles by both ELISA and
      Western blot and blocked NoV virus-like particle (VLP) and P particle binding to
      the histo-blood group antigen (HBGA) receptors with a BT(50) of about 1:800. The
      blocking activity of the chicken IgY remained after an incubation at 70 degrees C
      for 30min or treatments at pH 4-9 for 3h. These data suggested that chicken IgY
      could be a practical strategy for large-scale production of anti-NoV antibodies
      for potential use as passive immunization against NoV infection, as well as for
      diagnostic purposes.

PMID- 22867846
TI  - A new cell line (NTU-SE) from pupal tissues of the beet armyworm, Spodoptera
      exigua (Lepidoptera: Noctuidae), is highly susceptible to S. exigua multiple
      nucleopolyhedrovirus (SeMNPV) and Autographa californica MNPV (AcMNPV).
AB  - A new continuous cell line, NTU-SE, was established from the pupal tissues of an
      economically important pest, the beet armyworm Spodoptera exigua (Lepidoptera:
      Noctuidae). This cell line contains four major morphologic types: round,
      polymorphic, spindle-shaped, and comma-shaped cells. The population doubling time
      of this new line in TNM-FH medium supplemented with 8% fetal bovine serum (FBS)
      at 28 degrees C is 35.5h. The chromosomal spread from NTU-SE cells is typical to
      the chromosomal morphology of lepidopteran cell lines. Confidently, NTU-SE cell
      line is a new cell line that exhibits distinct isozyme patterns of esterase,
      lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) from those of the
      other insect cell lines. In addition, the DNA sequence of the nuclear ribosomal
      internal transcribed spacer (ITS) region of NTU-SE cells is above 96% identical
      to that sequence of S. exigua larvae, as compared to only 66% identical to that
      of S. litura larvae. The NTU-SE cell line is highly susceptible to S. exigua
      multiple nucleopolyhedrovirus (SeMNPV) and Autographa californica MNPV (AcMNPV).
      Therefore, a highly virulent SeMNPV strain, SeMNPV-1, had been successfully
      isolated and propagated in NTU-SE cells. We conclude that the NTU-SE cell line
      will be a useful tool for the selection and mass production of highly virulent
      SeMNPV strains for the S. exigua biocontrol and the baculovirus based recombinant
      protein expression systems.

PMID- 22867847
TI  - Cholesterol and breast cancer development.
AB  - Breast cancer is the most commonly occurring type of cancer in the world. Among
      the environmental factors believed to be responsible for this phenomenon,
      cholesterol has recently received considerable attention. Epidemiologic studies
      have provided inconclusive results, indicating that there may be a relationship
      between abnormal plasma cholesterol levels and breast cancer risk. However, more
      compelling evidence has been obtained in laboratory studies, and they indicate
      that cholesterol is capable of regulating proliferation, migration, and signaling
      pathways in breast cancer. In vivo studies have also indicated that plasma
      cholesterol levels can regulate tumor growth in mouse models. The recognition of
      cholesterol as a factor contributing to breast cancer development identifies
      cholesterol and its metabolism as novel targets for cancer therapy.

PMID- 22867848
TI  - Grapefruit juice and its constituents augment the effect of low pH on inhibition
      of survival and adherence to intestinal epithelial cells of Salmonella enterica
      serovar Typhimurium PT193.
AB  - The present study examined the survival of Salmonella Typhimurium and its
      adherence to intestinal epithelial cells following inoculation into grapefruit
      juice and apple cider. Both liquids significantly inactivated S. Typhimurium (0.8
      2.2 log reduction compared to the control); surviving Salmonella in grapefruit
      juice was 1.0-1.4 log lower than in apple cider at 24h incubation. Grapefruit
      juice contains the antimicrobial substances naringin (NAR) and naringenin (NGE);
      however, the effect of grapefruit juice on growth and adherence of S. Typhimurium
      appeared not to be related to NAR. NGE at 100-200 MUg/mL reduced the adherence of
      Salmonella to epithelial cells by 57% and 73% compared to the control (TSB at pH
      7.4) after 24 h treatment, but stimulated rather than inhibited growth of
      Salmonella. However, when NGE at 200 MUg/mL was added to TSB at pH 3.5 Salmonella
      survival and adherence to intestinal epithelial cells were reduced by 2.5 log and
      79%, respectively, compared to the control (TSB at pH 3.5). Addition of NGE to
      apple cider also caused a slight reduction in the survival of S. Typhimurium, but
      did not enhance the inhibitory effect on adherence due to apple cider. These data
      showed that low pH augmented the inhibitory effect of NGE on growth and adherence
      of Salmonella to intestinal epithelial cells, but the mechanism of the observed
      augmentative effect is not clear. Understanding the mechanism of the interaction
      between low pH and NGE and its inhibitory effect on growth and adherence of
      enteric pathogens may lead to the development of new antibacterial agents.

PMID- 22867849
TI  - ATP citrate lyase 1 (acl1) gene-based loop-mediated amplification assay for the
      detection of the Fusarium tricinctum species complex in pure cultures and in
      cereal samples.
AB  - The combined data set of the acl1 and tef-1alpha gene sequences of 61 fungal
      strains assigned to Fusarium tricinctum, Fusarium avenaceum, Fusarium acuminatum,
      Fusarium arthrosporioides, Fusarium flocciferum and Fusarium torulosum were used
      to study the phylogenetic relations between taxa. F. tricinctum, F. acuminatum
      and F. avenaceum formed distinct clades. Members of the F. tricinctum/F.
      acuminatum clade fall into three well supported lineages, of which the largest
      includes the epitype of F. tricinctum. Loop-mediated isothermal amplification
      (LAMP) was used to amplify a 167 bp portion of the acl1 gene in F. tricinctum
      (Corda) Saccardo. DNA amplification was detected in-tube by indirect calcein
      fluorescence under black light after 60 min of incubation at 65.5  degrees C. The
      assay had a detection limit of 0.95 pg of purified genomic DNA of F. tricinctum
      CBS 410.86 per reaction, corresponding to ca. 18 genomic copies of the acl1 gene.
      Specificity of the assay was tested using purified DNA from 67 species and
      subspecies of Fusarium as well as 50 species comprising 22 genera of other
      filamentous fungi and yeasts. The assay detected 21 of the 23 F. tricinctum
      strains tested. Cross reactivity was observed with eight out of 13 strains in F.
      acuminatum but with none of 17 F. avenaceum strains tested. Specificity was
      further confirmed by conventional PCR with primers designed from the same gene.
      Detection of F. tricinctum from culture scrapings directly added to the reaction
      master mix, in DNA extracts from wheat, in single barley grains or in washings of
      bulk grain samples are proposed as possible applications showing the suitability
      of the method for food analysis. Finally it was demonstrated that the LAMP
      reaction can be run using simple lab equipment such as a heating block, water
      bath, hybridization oven or household equipment, e.g. a microwave oven.

PMID- 22867850
TI  - Topogenesis of heterologously expressed fragments of the human Y4 GPCR.
AB  - Fragments of large membrane proteins have the potential to facilitate structural
      analysis by NMR, but their folding state remains a concern. Here we determined
      the quality of folding upon heterologous expression for a series of N- or C
      terminally truncated fragments of the human Y4 G-protein coupled receptor,
      amounting to six different complementation pairs. As the individual fragments
      lack a specific function that could be used to ascertain proper folding, we
      instead assessed folding on a basic level by studying their membrane topology and
      by comparing it to well-established structural models of GPCRs. The topology of
      the fragments was determined using a reporter assay based on C-terminal green
      fluorescent protein- or alkaline phosphatase-fusions. N-terminal fusions to Lep
      or Mistic were used if a periplasmic orientation of the N-terminus of the
      fragments was expected based on predictions. Fragments fused to Mistic expressed
      at comparably high levels, whereas Lep fusions were produced to a much lower
      extent. Though none of the fragments exclusively adopted one orientation, often
      the correct topology predominated. In addition, systematic analysis of the
      fragment series suggested that the C-terminal half of the Y4 receptor is more
      important for adopting the correct topology than the N-terminal part. Using the
      detergent dodecylphosphocholine, selected fragments were solubilized from the
      membrane and proved sufficiently stable to allow purification. Finally, as a
      first step toward reconstituting a functional receptor from two fragments, we
      observed a physical interaction between complementing fragments pairs upon co
      expression.

PMID- 22867851
TI  - HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting
      different susceptibility to HIV fusion inhibitors with pocket- or membrane
      binding domain.
AB  - Enfuvirtide (T20), the first FDA-approved peptide HIV fusion/entry inhibitor
      derived from the HIV-1 gp41 C-terminal heptad-repeat (CHR) domain, is believed to
      share a target with C34, another well-characterized CHR-peptide, by interacting
      with the gp41 N-terminal heptad-repeat (NHR) to form six-helix bundle core.
      However, our previous studies showed that T20 mainly interacts with the N
      terminal region of the NHR (N-NHR) and lipid membranes, while C34 mainly binds to
      the NHR C-terminal pocket region. But so far, no one has shown that C34 can
      induce drug-resistance mutation in the gp41 pocket region. In this study, we
      constructed pseudoviruses in which the Ala at the position of 67 in the gp41
      pocket region was substituted with Asp, Gly or Ser, respectively, and found that
      these mutations rendered the viruses highly resistant to C34, but sensitive to
      T20. The NHR-peptide N36 with mutations of A67 exhibited reduced anti-HIV-1
      activity and decreased alpha-helicity. The stability of six-helix bundle formed
      by C34 and N36 with A67 mutations was significantly lower than that formed by C34
      and N36 with wild-type sequence. The combination of C34 and T20 resulted in
      potent synergistic anti-HIV-1 effect against the viruses with mutations in either
      N- or C-terminal region in NHR. These results suggest that C34 with a pocket
      binding domain and T20 containing the N-NHR- and membrane-binding domains inhibit
      HIV-1 fusion by interacting with different target sites and the combinatorial use
      of C34 and T20 is expected to be effective against HIV-1 variants resistant to
      HIV fusion inhibitors.

PMID- 22867852
TI  - A field evaluation of a footbathing solution for the control of digital
      dermatitis in cattle.
AB  - Footbathing is one of the most commonly used methods for controlling digital
      dermatitis (DD). A farm-based trial was undertaken using six dairy herds
      involving over 600 cubicle-housed Holstein-Friesian cattle. Split footbaths
      (length 2.2m) were used to compare the efficacy of two dips, namely, a positive
      control (5% copper sulphate) and a non-heavy metal-based proprietary dip. The
      dips were used from early January 2009 for a minimum of 103 days, bathing twice a
      day for 3 consecutive days every week, using one footbath (three herds) or two in
      line (three herds). The lesions of DD on the hind feet of cattle were scored by
      borescope while the animals were being milked, on three occasions (at
      approximately days 0, 55 and 110) and then compared both directly and by
      calculating the change in severity from the previous examination (when possible).
      Data from the 408 cows that had their feet examined for lesions on all three
      occasions were analysed separately. A reduction in lesion score was seen for both
      footbath products, but feet bathed in 5% copper sulphate improved more (OR=1.6,
      CI: 1.14-2.32; P<0.01), and, irrespective of solution, there was a significantly
      greater improvement in those herds where two footbaths were used (OR=3.39, CI:
      2.07-5.19; P<0.001). Lesion improvement over time also increased with lactation
      number (OR=1.13, CI: 1.02-1.25; P<0.05).

PMID- 22867853
TI  - An investigation into the use of infrared thermography (IRT) as a rapid
      diagnostic tool for foot lesions in dairy cattle.
AB  - Previous research has suggested that temperature at the coronary band increases
      in the presence of claw horn lesions in dairy cattle. However the reliability of
      using infrared thermography (IRT) as a method of distinguishing between lesions
      has not been investigated. The objective of this study was to examine the
      potential of IRT as a non-invasive tool for rapidly screening for the presence of
      digital dermatitis (DD). Eighty-two cows which either had no skin lesions on the
      hind feet (controls, n=41 feet) or a DD lesion on one or both feet were selected
      during milking. Following selection, each cow was moved into the farm crush where
      thermal images were taken from the plantar aspect of each foot at the pastern
      when the foot was dirty, cleaned and raised for visual inspection. Following
      recording of thermal images each hind foot was trimmed and the presence of any
      lesion recorded. It was found that the temperature did not differ significantly
      between feet with DD lesions and other skin or claw horn lesions, regardless of
      whether the feet were dirty, clean or raised for inspection. As IRT was not
      sensitive enough for lesion specific detection, the reliability of setting a
      temperature threshold above which any type of lesion causing lameness could be
      detected was investigated. The optimal trade off between sensitivity and
      specificity could be reached without having to either clean or lift the feet.
      Setting the threshold for disease at 27 degrees C for dirty feet identified 80%
      of feet with lesions and 73% of feet without lesions correctly. In conclusion,
      IRT was reliable in detecting elevated temperature associated with foot lesions.
      Future research investigating the development of lesions may identify a
      temperature threshold for early treatment intervention. This technique may also
      be useful to quantify the effectiveness of early treatment by tracking recovery
      and recurrence of cases.

PMID- 22867854
TI  - The effect of an acidified, ionized copper sulphate solution on digital
      dermatitis in dairy cows.
AB  - Digital dermatitis (DD) is the most important infectious claw disorder in dairy
      cattle and herd-based foot bathing with antibacterials, such as 4% formalin, is
      often used to prevent it. However, there is a lack of long-term studies of the
      effectiveness of such regimes and in this study the preventive and curative
      effect of 4% formalin was compared with that of an acidified, ionized copper
      sulphate solution over a 4-month period on a commercial 120-cow dairy farm. The
      cows were walked through a split-leg footbath where left claws were treated with
      an acidified copper solution twice daily for 5 days/week, while right claws were
      treated with 4% formalin twice daily for 1 day/every second week. Hind claws were
      scored for the presence and severity of DD in a trimming chute at the start of
      the study and every 4 weeks throughout the study period. At the start of the
      study 21/110 cows had ulcerative DD lesions with 10 on the left hind foot, 8 on
      the right and 3 on both. These lesions, as well as any new lesions which arose
      during the study, were treated with chlortetracycline spray. During the study 440
      observations were made and seven new DD lesions were recorded on left feet
      (copper treated) and 20 on right feet (formalin treated). Based on survival
      analysis, the risk of developing a new ulcerative DD lesion on copper-treated
      (left hind) feet was almost three times less (RR=0.37, 95% CI 0.16-0.91) than
      formalin-treated (right hind) feet. Cure rates of DD lesions were not different
      between copper and formalin.

PMID- 22867855
TI  - Feline leukaemia virus: half a century since its discovery.
AB  - In the early 1960s, Professor William (Bill) F.H. Jarrett was presented with a
      time-space cluster of cats with lymphoma identified by a local veterinary
      practitioner, Harry Pfaff, and carried out experiments to find if the condition
      might be caused by a virus, similar to lymphomas noted previously in poultry and
      mice. In 1964, the transmission of lymphoma in cats and the presence of virus
      like particles that resembled 'the virus of murine leukaemias' in the induced
      tumours were reported in Nature. These seminal studies initiated research on
      feline leukaemia virus (FeLV) and launched the field of feline retrovirology.
      This review article considers the way in which some of the key early observations
      made by Bill Jarrett and his coworkers have developed in subsequent years and
      discusses progress that has been made in the field since FeLV was first
      discovered.

PMID- 22867856
TI  - Comparative epidemiology of tendon injuries in different racing disciplines.

PMID- 22867857
TI  - Surgical considerations about amyloid goiter.
AB  - Amyloidosis is an uncommon syndrome consisting of a number of disorders having in
      common an extracellular deposit of fibrillary proteins. This results in
      functional and structural changes in the affected organs, depending on deposit
      location and severity. Amyloid infiltration of the thyroid gland may occur in 50%
      and up to 80% of patients with primary and secondary amyloidosis respectively.
      Amyloid goiter (AG) is a true rarity, usually found associated to secondary
      amyloidosis. AG may require surgical excision, usually because of compressive
      symptoms. We report the case of a patient with a big AG occurring in the course
      of a secondary amyloidosis associated to polyarticular onset juvenile idiopathic
      arthritis who underwent total thyroidectomy. Current literature is reviewed, an
      attempt is made to provide action guidelines, and some surgical considerations on
      this rare condition are given.

PMID- 22867858
TI  - Distributed static linear Gaussian models using consensus.
AB  - Algorithms for distributed agreement are a powerful means for formulating
      distributed versions of existing centralized algorithms. We present a toolkit for
      this task and show how it can be used systematically to design fully distributed
      algorithms for static linear Gaussian models, including principal component
      analysis, factor analysis, and probabilistic principal component analysis. These
      algorithms do not rely on a fusion center, require only low-volume local (1-hop
      neighborhood) communications, and are thus efficient, scalable, and robust. We
      show how they are also guaranteed to asymptotically converge to the same solution
      as the corresponding existing centralized algorithms. Finally, we illustrate the
      functioning of our algorithms on two examples, and examine the inherent cost
      performance trade-off.

PMID- 22867859
TI  - Repair of restorations--criteria for decision making and clinical
      recommendations.
AB  - OBJECTIVES: In the last decade, repair of restorations has become more and more
      popular while teaching repair of restorations is now included in most
      universities in Europe and North America. The aim of this paper was therefore to
      systematically review the clinical and the in vitro aspects of repair of
      restorations by considering different restorative materials--resin-based
      composites, amalgam, glass-ionomer cements, ceramics or metals. The paper gives
      also an overview of the occurrences of teaching repair in different universities.
      Furthermore, the paper outlines criteria for decision making when to treat a
      defect restoration with refurbishment, repair, replacement or no treatment. DATA:
      The database search strategy for resin based composite restoration repair (n=360)
      and the following hand search (n=95) retrieved 455 potentially eligible studies.
      After de-duplication, 260 records were examined by the titles and abstracts. 154
      studies were excluded and 106 articles were assessed for eligibility by analyzing
      the full texts. Following the same search and selection process, 42 studies for
      amalgam repair, 51 studies for cast, inlay or porcelain restoration repair and 8
      studies for teaching were assessed for eligibility by analysis of the full texts.
      SOURCES: Following databases were analyzed: Cochrane Library, MEDLINE, EMBASE,
      BIOSIS and PUBMED. STUDY SELECTION: Papers were selected if they met the
      following criteria: replacement, refurbishment or repair of resin composite
      restorations or amalgam restorations or inlay, cast restoration or porcelain
      repair. Clinical studies, in vitro studies and reports about teaching were
      included. CONCLUSIONS: Repair of restoration is a valuable method to improve the
      quality of restorations and is accepted, practiced and taught in many
      universities. However, there is a need for methodologically sound randomized
      controlled long-term clinical trials to be able to give an evidence based
      recommendation.

PMID- 22867861
TI  - Proton-promoted dissolution of alpha-FeOOH nanorods and microrods: size
      dependence, anion effects (carbonate and phosphate), aggregation and surface
      adsorption.
AB  - Iron-containing oxide nanoparticles are of great interest from a number of
      technological perspectives and they are also present in the natural environment.
      Although recent evidence suggests that particle size plays an important role in
      the dissolution of metal oxides, a detailed fundamental understanding of the
      influence of particle size is just beginning to emerge. In the current study, we
      investigate whether nanoscale size-effects are observed for the dissolution of
      iron oxyhydroxide under different conditions. The dissolution of two particle
      sizes of goethite, alpha-FeOOH in the nanoscale and microscale size regimes
      (herein referred to as nanorods and microrods), in aqueous suspensions at pH 2 is
      investigated. It is shown here that in the presence of nitrate, nanorods shows
      greater dissolution on both a per mass and per surface area basis relative to
      microrods, in agreement with earlier studies. In the presence of carbonate and
      phosphate, however, dissolution of alpha-FeOOH nanorods at pH 2 is significantly
      inhibited, despite the fact that these anions result in a three- to fivefold
      enhancement of the dissolution of microrods relative to the nitrate anion. Light
      scattering techniques and electron microscopy show that nanorod suspensions are
      less stable compared to microrod suspensions resulting in nanorod aggregation
      under conditions where microrods stay more dispersed. Furthermore, spectroscopic
      studies using ATR-FTIR spectroscopy show distinct differences in phosphate and
      carbonate adsorption on nanorods compared to microrods. These results demonstrate
      that aggregation and the details of surface adsorption are important in the
      dissolution behavior of nanoscale materials.

PMID- 22867860
TI  - Preparation and structure evolution of bowknot-like calcium carbonate particles
      in the presence of poly(sodium 4-styrene sulfate).
AB  - Calcium carbonate particles with a novel bowknot-like superstructure were
      fabricated in the presence of poly(sodium 4-styrene sulfate) (PSS) and under the
      assistance of ultrasonication during the initial reaction stage. X-ray powder
      diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission
      electron microscopy (TEM), selected area electron diffraction (SAED), and field
      emission scanning electron microscopy (FE-SEM) equipped with energy-dispersive X
      ray (EDX) were used to characterize the particles. Results demonstrated that the
      bowknot-like calcium carbonate particles were mainly composed of amorphous
      calcium carbonate (ACC) and some amounts of calcite and vaterite. Ultrasound
      irradiation associated with the presence of PSS affects the mesoscale
      crystallization, resulting in stepwise growth of the earlier bundles to the
      bowknot. Morphology evolution and dissolution of the bowknot particle were
      observed in different media, confirming that PSS and Ca(2+) ions in the solutions
      could accelerate and resist the transformation process, respectively. In the
      presence of PSS, ACC prefers to transform into vaterite.

PMID- 22867862
TI  - Chronic doxorubicin cardiotoxicity modulates cardiac cytochrome P450-mediated
      arachidonic acid metabolism in rats.
AB  - Doxorubicin [(DOX) Adriamycin] is an effective anticancer agent whose major
      limiting side effect is cardiotoxicity. This cardiotoxicity is predicted only by
      the cumulative dose of DOX where the clinical situation involves chronic drug
      administration. Therefore, we investigate the effect of chronic DOX
      cardiotoxicity on expression of the cardiac cytochrome P450 (P450) enzymes and
      arachidonic acid (AA) metabolism in male Sprague-Dawley (SD) rats. The chronic
      toxicity was induced by multiple intraperitoneal injections for a cumulative dose
      of 15 mg/kg divided into six injections within 2 weeks. After 14 days of the last
      injection, the heart, liver, and kidney were harvested, and the expression of
      different genes was determined by real-time polymerase chain reaction. In
      addition, microsomal protein from the heart was prepared and incubated with AA.
      Thereafter, different AA metabolites were analyzed by liquid chromatography
      electrospray ionization-mass spectrometry. The chronic DOX cardiotoxicity
      significantly induced gene expression of hypertrophic markers, apoptotic markers,
      CYP2E1, CYP4A3, CYP4F1, CYP4F5, and soluble epoxide hydrolase (sEH) enzyme, which
      was accompanied by an increase in the activity of P450 omega-hydroxylases and
      sEH. In addition, both the sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)
      cyclohexyloxy]-benzoic acid, and the omega-hydroxylase inhibitor, N-hydroxy-N'-(4
      butyl-2-methylphenyl)-formamidine (HET0016), significantly prevented the DOX
      mediated induction of the hypertrophic markers in the cardiac-derived H9c2 cells,
      which further confirms the role of these enzymes in DOX cardiotoxicity.
      Furthermore, gene expression of P450 and sEH was altered in an organ-specific
      manner. As a result, the chronic DOX administration leads to an imbalance between
      P450-mediated cardiotoxic and cardioprotective pathways. Therefore, P450 omega
      hydroxylases and sEH might be considered as novel targets to prevent and/or treat
      DOX cardiotoxicity.

PMID- 22867863
TI  - Heavy agricultural workloads and low crop diversity are strong barriers to
      improving child feeding practices in the Bolivian Andes.
AB  - Most nutrition initiatives to date aimed at improving infant and young child
      feeding (IYCF) have emphasized addressing knowledge gaps through behavior change
      messaging with less focus on addressing the underlying environmental barriers
      that may shape these behaviors. This research integrates an analysis of
      longitudinal dietary data with qualitative data on barriers to improved child
      feeding to identify the nature and extent of the barriers caregivers face to
      improving IYCF practices in a farming region of the Bolivian Andes, and to
      determine the relative influence of these barriers on caregivers' abilities to
      improve IYCF practices. Sixty-nine caregivers were selected from a sample of 331
      households that participated in a longitudinal survey assessing changes in IYCF
      practices among caregivers with children aged 0-36 months from March 2009 to
      March 2010. Forty-nine barriers within 12 categories of barriers were identified
      through semi-structured interviews with the 69 caregivers. The most frequently
      reported barriers were those related to women's time dedicated to agricultural
      labor, the limited diversity of household agricultural production, and lack of
      support for child feeding from spouses and mothers-in-law. In multivariate
      analyses controlling for several variables that could potentially influence IYCF
      practices, these barriers were negatively associated with changes to the
      diversity of child diets, child dietary energy intake, and child meal frequency.
      While knowledge gaps and individual-level influences affected IYCF practices,
      physical and social caregiving environments in this region of Bolivia were even
      more important. Behavior change communication alone will likely not address the
      social and environmental barriers to improved child feeding that often prevent
      translation of improved knowledge into action. Particularly in rural regions,
      agriculture may strongly influence child feeding, not only indirectly through
      household food security, but also directly by affecting women's caregiving
      capacity.

PMID- 22867864
TI  - Impact of gender-based career obstacles on the working status of women physicians
      in Japan.
AB  - Research has shown that women physicians work fewer hours and are more likely to
      become inactive professionally and to switch to part-time labor, compared with
      their male counterparts. The published literature suggests that a gender
      disparity still exists in medicine which may decrease work motivation among women
      physicians. The authors investigated whether the experience and the perception of
      gender-based career obstacles among women physicians in Japan are associated with
      their working status (i.e., full-time vs. part-time). The present cross-sectional
      study is based on surveys of alumnae from 13 private medical schools in Japan
      conducted between June 2009 and May 2011. Of those who agreed to participate in
      this study, 1684 completed a self-administered questionnaire (overall response
      rate 83%). Experience of gender-based obstacles was considered affirmative if a
      woman physician had been overlooked for opportunities of professional advancement
      based on gender. Perception of gender-based obstacles referred to the self
      reported degree of difficulty of promotion and opportunities for a position in
      higher education. Approximately 20% of the study participants responded that they
      experienced gender-based obstacles while 24% answered that they were not sure.
      The scores for perception of gender-based career obstacles were statistically
      higher among part-time workers compared with full-time workers (mean difference =
      1.20, 95% CI: 0.39-2.00). Adjusting for age, marital status, the presence of
      children, workplace, board certification, holding a PhD degree, overall
      satisfaction of being a physician, and household income, stepwise logistic
      regression models revealed that physicians with the strongest perception of
      gender-based career obstacles were more likely to work part-time rather than full
      time (OR, 0.59; 95% CI: 0.40-0.88). Although the experience of gender-based
      obstacles was not associated with working status among women physicians, the
      results demonstrated that a strong perception of gender-based obstacles was
      associated with part-time practice rather than full-time practice.

PMID- 22867865
TI  - Involving citizens in the ethics of biobank research: informing institutional
      policy through structured public deliberation.
AB  - This paper reports on the design, implementation, and results of a structured
      public deliberation on human tissue biobanking conducted in Vancouver, Canada, in
      2009. This study builds on previous work on the use of deliberative democratic
      principles and methods to engage publics on the social and ethical implications
      of human tissue biobanking. In a significant refinement of methods, we focus on
      providing public input to institutional practice and governance of biobanks using
      a tailored workbook structure to guide participants' discussion. Our focus is on
      the local context and practices of a particular institution, the BC BioLibrary.
      However, elements of both the methodological innovations and the ethical guidance
      implied by our findings are generalisable for biobanking internationally.
      Recommendations from the deliberative forum include issues of informed consent,
      privacy protections, collection of biospecimens, governance of biobanks, and how
      to manage the process of introduction between biobanks and potential donors.
      Notable findings include public support for research use of anonymised un
      consented tissue samples when these come from archived collections, but lack of
      support when they are collected prospectively.

PMID- 22867866
TI  - Argentum-quarz solution in the treatment of anorectal fistulas: is it possible a
      conservative approach?
AB  - Patients suffering from chronic intestinal diseases (Crohn's disease, Ulcerative
      Colitis, Indeterminate Colitis) are prone to the development of pyogenic
      complications. These complications are most commonly in the form of perianal or
      intraabdominal abscesses and/or fistulas. The treatment of these complications
      are managed differently but, after an initial treatment based on medical or
      minimally invasive management, the solution of the pathological condition is
      always achieved by a surgical procedure. In the last few years prospective
      studies have proposed an alternative conservative therapeutic approach based on
      application of fibrin glue in the healing of patients with fistulas-in-ano. In
      this paper we suggest and discuss the therapeutic potential of silver and quarz
      in the conservative treatment of anorectal fistulas pointing out their role in
      modulating particular steps of the pathogenetic process which characterizes this
      pathological condition.

PMID- 22867867
TI  - A case for combined ovarian and breast cancer prevention.
AB  - Targeted prevention of ovarian cancer is hindered by the inaccessibility of
      ovarian tissue, lack of accepted biomarkers and low disease incidence. However,
      ovarian cancer has common risk factors and shared etiologies with breast cancer.
      Chemoprevention of ovarian cancer has been demonstrated incidentally during
      testing of novel breast cancer prevention drugs. Here it is hypothesized that the
      development of combined ovarian and breast cancer prevention strategies is a
      preferable strategy for ovarian cancer prevention.

PMID- 22867868
TI  - HPV16 activates the promoter of Oct4 gene by sequestering HDAC1 from repressor
      complex to target it to proteasomal degradation.
AB  - Human papillomavirus 16 (HPV16) is the key factor to initiate cervical
      carcinogenesis and development. Octamer-binding transcription factor 4 (Oct4) is
      an important transcriptional factor which is up-regulated in some cancer cells.
      Our study showed that the expression of Oct4 might be activated by HPV16
      infection. Both the levels of histone deacetylase 1 (HDAC1) and DNA
      methyltransferase 3A (DNMT3A) were negatively correlated with the level of Oct4
      in cervical cancer cells. Moreover, HDAC1 and DNMT3A proteins were in the same
      complex, the level of which was higher in the presence of HPV16. The treatment
      with HDAC1 inhibitor reduced the level of this complex, followed by the
      upregulation of Oct4 expression. Based on these findings and previous reports, we
      hypothesize that a repressor complex containing methyl CpG-binding domain protein
      2 (MBD2), DNMT3A and HDAC1 binds to the hyper-methylated regulatory regions of
      Oct4 gene to facilitate forming a close chromatin which results in the
      suppression of Oct4 transcription in cervical cells. The oncoproteins of HPV16
      synergistically sequester HDAC1 protein from repressor complex, and target it to
      ubiquitin mediated proteasome degradation. The repressor complex is thus
      destroyed and the close chromatin is relaxed, which eventually lead to the
      upregulation of Oct4 expression.

PMID- 22867869
TI  - Central TSC2 missense mutations are associated with a reduced risk of infantile
      spasms.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome with a
      variable neurocognitive phenotype. Recently, different intelligence profiles were
      observed for distinct mutation types and locations, suggesting that individuals
      with missense mutations represent a subgroup with milder neurocognitive outcomes.
      We applied these recent insights to the analysis of the epilepsy phenotype in a
      large cohort of patients with TSC. Associations between genotype and a history of
      epilepsy and/or infantile spasms (IS) were explored retrospectively, using data
      from 478 TSC patients from the databases of the Tuberous Sclerosis Alliance and
      the Herscot Center at Massachusetts General Hospital. Absolute and relative risks
      for IS and other types of epilepsy were calculated for various mutation classes,
      selected according to type and location. As expected, TSC2 mutations were
      associated with a significantly higher occurrence of IS and other epilepsy types.
      However, missense mutations located in the central region of TSC2 (exons 23-33)
      were associated with a significantly reduced incidence of IS. Our study further
      delineates the epilepsy phenotype in TSC patients. Identifying distinct epilepsy
      phenotypes for specific mutation subgroups may help identify relevant biomarkers
      and assist clinicians in making treatment decisions.

PMID- 22867870
TI  - Sugary beverages represent a threat to global health.
AB  - Sugary beverages represent a major global threat to the health of all
      populations. The shifts in distribution, marketing, and sales have made them the
      plague of the globe in terms of obesity, diabetes, and a host of other chronic
      health problems. The fructose-laden beverages have unique properties that lead to
      lack of dietary compensation and direct adverse effects on our health. Global
      efforts to limit marketing and sales are necessary to protect the health of the
      planet.

PMID- 22867872
TI  - Porcine T-helper and regulatory T cells exhibit versatile mRNA expression
      capabilities for cytokines and co-stimulatory molecules.
AB  - T-helper (TH) and regulatory T cells (Tregs) are important modulators of immune
      responses. Aim of this study was to analyse their expression potential for
      cytokines and other immune-relevant molecules. Therefore, porcine PBMC, CD4(-)
      cells, CD4(+)CD25(-) resting, CD4(+)CD25(dim) activated TH cells, and
      CD4(+)CD25(high) Tregs were analysed on their mRNA expression potential ex vivo
      or after in vitro stimulation with CD3 and IL-2 by RT-qPCR. In vitro stimulation
      led to an increased production of pro-inflammatory (IL-6, TNFalpha) and TH (IL-2,
      IL-4, IL-17, IFN-gamma) cytokines and a diverse production of immunosuppressive
      cytokines (IL-10 and TGF-beta) in PBMC, CD4(-), and CD4(+) cells. Resting and
      activated TH cells showed an increased expression of various immune-modulatory
      molecules indicating that porcine TH cells possess distinct immunological skills
      in order to react on the actual immune situation. In contrast, Tregs appear to
      fulfil mainly immunosuppressive functions characterized by increased production
      of IL-10, IL-35, CD40L, and CD25.

PMID- 22867871
TI  - Delayed developmental changes in neonatal vocalizations correlates with
      variations in ventral medial hypothalamus and central amygdala development in the
      rodent infant: effects of prenatal cocaine.
AB  - While variations in neonatal distress vocalizations have long been shown to
      reflect the integrity of nervous system development following a wide range of
      prenatal and perinatal insults, a paucity of research has explored the
      neurobiological basis of these variations. To address this, virgin Sprague-Dawley
      rats were bred and divided into three groups: [1] untreated, [2] chronic-cocaine
      treated (30 mg/kg/day, gestation days (GDs) 1-20); or [3] chronic saline treated
      (2 mg/kg/day, GDs 1-20). Pregnant dams were injected with Bromodeoxyuridine (10
      mg/kg) on GDs 13-15 to label proliferating cells in limbic regions of interest.
      Ultrasonic vocalizations (USVs) were recorded on postnatal days (PNDs) 1, 14, and
      21, from one male and female pup per litter. Variations in acoustic properties of
      USVs following cocaine-exposure were age and sex-dependent including measures of
      total number, total duration and amplitude of USVs, and percent of USVs with at
      least one harmonic. Following USV testing brains were stained with standard
      fluorescent immunohistochemistry protocols and examined for variations in
      neuronal development and if variations were associated with acoustic
      characteristics. Limbic region developmental differences following cocaine
      exposure were sex- and age-dependent with variations in the ventral medial
      hypothalamus and central amygdala correlating with variations in vocalizations on
      PND 14 and 21. Results suggest maturation of the ventral medial hypothalamus and
      central amygdala may provide the basis for variations in the sound and production
      of USVs. As vocalizations may serve as a neurobehavioral marker for nervous
      system integrity, understanding the neurobiological basis of neonatal
      vocalizations may provide the basis for early intervention strategies in high
      risk infant populations.

PMID- 22867873
TI  - Chromatin modifications as therapeutic targets in MLL-rearranged leukemia.
AB  - MLL-rearranged leukemias exemplify malignancies with perturbations of the
      epigenetic landscape. Specific chromatin modifications that aid in the
      perpetuation of MLL fusion gene driven oncogenic programs are being defined,
      presenting novel avenues for therapeutic intervention. Proof-of-concept studies
      have recently been reported, using small-molecule inhibitors targeting the
      histone methyltransferase disruptor of telomeric silencing 1-like (DOT1L), or the
      acetyl-histone binding protein bromodomain containing protein 4 (BRD4) showing
      potent activity against MLL-rearranged leukemias in preclinical models. It is
      apparent that intensive efforts will be made toward the further development of
      small-molecule inhibitors targeting these, and other chromatin-associated protein
      targets. These studies may lead to the advent of a new generation of much-needed
      therapeutic modalities in leukemia and other cancers.

PMID- 22867875
TI  - Homocysteine activates vascular smooth muscle cells by DNA demethylation of
      platelet-derived growth factor in endothelial cells.
AB  - Hyperhomocysteinemia (HHcy), as an independent risk factor of atherosclerosis,
      facilitates endothelial dysfunction and activation of vascular smooth muscle
      cells (VSMCs). However, little is known about the crosstalk between endothelial
      cells (ECs) and VSMCs under HHcy. We investigated whether homocysteine (Hcy)
      activates VSMCs by aberrant secretion of mitogen platelet-derived growth factors
      (PDGFs) from ECs in human and in mice. In this study, we found that increased Hcy
      level did not affect VSMC activity in 24 hrs until the concentration reached 500
      MUM. In contrast, Hcy at 100 MUM significantly promoted proliferation and
      migration of VSMCs co-cultured with human ECs. This effect was partially reversed
      by pretreatment with a PDGF receptor inhibitor. Hcy concentration-dependently
      upregulated the mRNA level of PDGF-A, -C and -D but not PDGF-B in ECs. Hcy
      reduced the expression and activity of DNA methyltransferase 1, demethylation of
      PDGF-A, -C and -D promoters and enhanced the binding activity of transcriptional
      factor SP-1 to the promoter. Hcy upregulation of PDGF was confirmed in the aortic
      intima of mice with HHcy. Multivariate regression analysis revealed HHcy was a
      predictor of increased serum PDGF level in patients. Thus, Hcy upregulates PDGF
      level via DNA demethylation in ECs, affects cross-talk between ECs and VSMCs and
      leads to VSMC activation.

PMID- 22867874
TI  - Developing strategies for HIV-1 eradication.
AB  - Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication,
      transforming the outlook for infected patients. However, reservoirs of
      replication-competent forms of the virus persist during HAART, and when treatment
      is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1
      latency, as well as a report that HIV-1 infection was eradicated in one
      individual, have renewed interest in finding a cure for HIV-1 infection.
      Strategies for HIV-1 eradication include gene therapy and hematopoietic stem cell
      transplantation, stimulating host immunity to control HIV-1 replication, and
      targeting latent HIV-1 in resting memory CD4(+) T cells. Future efforts should
      aim to provide better understanding of how to reconstitute the CD4(+) T cell
      compartment with genetically engineered cells, exert immune control over HIV-1
      replication, and identify and eliminate all viral reservoirs.

PMID- 22867876
TI  - A novel method for the purification of low soluble recombinant C-type lectin
      proteins.
AB  - Snake venoms contain a complex mixture of many biological molecules including
      proteins. The purification of recombinant proteins is a key step in studying
      their function and structure with affinity chromatography as the common method
      used in their purification. In bacterial expression systems, hydrophobic
      recombinant proteins are usually precipitated into inclusion bodies, and
      contaminants are typically associated with tagged proteins after purification.
      The purpose of this study was to develop a procedure to purify hydrophobic
      recombinant proteins without an affinity tag. Snake venom mature C-type lectin
      like proteins (CLPs) with a tag were cloned, expressed, and purified by repeated
      sonication and wash steps. The effects of the signal peptide on the expression
      and solubility of the recombinant protein were investigated. The CLPs in washed
      inclusion bodies were solubilized and refolded by dialysis. The CLPs without a
      tag were successfully purified with a yield 38 times higher than the traditional
      method, and inhibited blood platelet aggregation with an IC(50) of 100.57 MUM in
      whole blood. This novel procedure is a rapid, and inexpensive method to purify
      functional recombinant hydrophobic CLPs from snake venoms useful in the
      development of drug therapies.

PMID- 22867880
TI  - Impaired cardiac microvascular endothelial cells function induced by
      Coxsackievirus B3 infection and its potential role in cardiac fibrosis.
AB  - CVB3 virus tropism and tissue access are modulated by cardiac microvascular
      endothelial cells (CMVECs) in the context of microvasculature. This study was
      designed to examine biological behaviors of CMVECs following CVB3 infection and
      its possible effects on cardiac remodeling. Data demonstrated that CVB3 increased
      caspase-3 activities, Bax/Bcl-2 protein ratio and TGF-beta1 levels in CMVECs,
      accompanying with elevated microvascular permeability. Double immunofluorescence
      revealed co-localization of endothelial markers (CD31 and VE-cadherin) and
      mesenchymal markers (FSP1 and alphaSMA) in infected CMVECs. Western blot
      demonstrated that CVB3 significantly decreased the expression of endothelial
      markers and increased the expression of mesenchymal markers, which were reversed
      by SB431542 (inhibitor of TGF-beta1), indicating that endothelial-to-mesenchymal
      transition following CVB3 infection was probably induced by CMVECs-derived TGF
      beta1. Excess extracellular matrix was produced by myocardial cells incubated
      with supernatants of infected CMVECs. Our results displayed that CVB3 induced
      notable biological changes of CMVECs, which may contribute to cardiac fibrosis.

PMID- 22867881
TI  - Antibiotic resistance of Vibrio cholerae O1 El Tor strains from the seventh
      pandemic in China, 1961-2010.
AB  - Antibiotic resistance is observed with increasing frequency among epidemic Vibrio
      cholerae strains in some countries. In this study, the antibiotic resistance
      profiles of V. cholerae O1 El Tor strains isolated in China from 1961 to 2010
      were analysed. The frequency of antibiotic resistance among the seventh pandemic
      El Tor isolates from China remained low, except for resistance to nalidixic acid
      (45.9%), tetracycline (11%) and trimethoprim/sulfamethoxazole (38.5%). All test
      strains in the first multiyear epidemic in the 1960s were sensitive to all test
      antibiotics, whereas strains from the 1990s and later showed a rapid increase in
      the prevalence of resistance. The class I integron was present primarily among
      strains isolated between 1993 and 1998, and the prevalence of the SXT element was
      much greater among strains isolated after 1993. This study determined the
      regional resistance characteristics of epidemic clones in China and serves as a
      warning of the rapid dissemination of resistance in the past 20 years.

PMID- 22867882
TI  - Updates on the global prevalence of MRSA: results from Iran.

PMID- 22867883
TI  - Evaluation of the in vitro and intracellular efficacy of new monosubstituted
      sulfonylureas against extensively drug-resistant tuberculosis.
AB  - Acetohydroxyacid synthase (AHAS) has been regarded as a potential drug target
      against Mycobacterium tuberculosis as it catalyses the first step in the pathway
      for biosynthesis of branched-chain amino acids. In our previous work, several
      monosubstituted sulfonylureas that are inhibitors of AHAS showed obvious in vitro
      activity against M. tuberculosis. In this study, further exploration of the
      antitubercular activity of newly synthesised monosubstituted sulfonylureas was
      conducted. A series of new compounds were identified that exhibit significant
      activity against in vitro and intracellular extensively drug-resistant M.
      tuberculosis. These results provide a further insight into the structural
      requirements for targeting AHAS to develop potential new agents to combat
      tuberculosis.

PMID- 22867884
TI  - An exploratory study of brain function and structure in mucopolysaccharidosis
      type I: long term observations following hematopoietic cell transplantation
      (HCT).
AB  - AIM: Although hematopoietic cell transplantation (HCT) arrests the cognitive
      decline in mucopolysaccharidosis type IH (Hurler syndrome, MPS IH), these
      children continue to have neuropsychological deficits as they age. Both
      compromised attention and effects on white matter have been observed in cancer
      patients who have had chemotherapy. Therefore, we explored the effects of disease
      and treatment on brain function in children with MPS I who have had HCT with
      those with attenuated MPS I treated with enzyme replacement therapy (ERT).
      METHODS:  SUBJECTS: 7 MPS IH participants at least 5 years post-HCT were compared
      with 7 attenuated participants who were treated with ERT. MEASURES: IQ,
      attention, spatial ability, and memory were assessed. Medical history and an
      unsedated MRI scan using diffusion tensor imaging (DTI) were acquired. RESULTS:
      Despite clinically equivalent IQ and memory, children with MPS IH had poorer
      attention span than those with attenuated MPS I as well as decreased fractional
      anisotropy (FA) of the corpus callosum. A relationship between attention scores
      and FA was found in the MPS IH group but not the attenuated group. FA was also
      related to the frequency of medical events. INTERPRETATION: In children with MPS
      IH, both the treatment and the disease affect attention functions associated with
      poor white matter integrity.

PMID- 22867885
TI  - Acute leukemias in children with Down syndrome.
AB  - Children with Down syndrome (DS) often present with hematopoietic abnormalities,
      and are at increased risk of developing leukemia. Specifically, 3-10% of newborns
      with DS are diagnosed with transient myeloproliferative disease, and children
      with DS are 500 times more likely to develop acute megakaryoblastic leukemia
      (AMKL) and 20 times more likely to develop acute lymphoblastic leukemia (ALL)
      than typical children. This review examines the characteristics of these
      leukemias and their development in the unique genetic background of trisomy 21. A
      discussion is also provided for areas of future research and potential
      therapeutic development.

PMID- 22867886
TI  - Why cancer survivors have a lower risk of Alzheimer disease.
AB  - Tying up two recent lines of experimental evidence may help explain this vital
      issue. On the one hand, data indicate that cancerous transformations of cells
      include changes in expression level and/or the functionality of multidrug
      resistance modulators which then disturb chemotherapy. On the other hand, studies
      have shown that some of the ABC transporters--at the blood-brain barrier--work as
      effective efflux pumps for amyloid Abeta peptides. Amyloid Abeta peptides, cut
      from the amyloid precursor protein of neurons can be assumed to induce brain wide
      neuronal apoptosis via opening plasma lemma-standing type-1 VDAC/porin channels
      as shown by in vitro experiments using established neuronal cell lines. However,
      extrusion of apoptosis inductive Abeta by increased ABC transporter activity at
      the blood-brain barrier from the brain of cancer survivors might abolish this
      effect. The hypothesis presented can be read as a clue on what in recent
      literature is referred to as the inverse association of cancer and Alzheimer
      disease.

PMID- 22867887
TI  - Accelerated clinical disease and pathology in mucopolysaccharidosis type IIIB and
      GalNAc transferase double knockout mice.
AB  - Mucopolysaccharidosis type IIIB (MPS IIIB) is a neuropathic lysosomal storage
      disorder (LSD) resulting from an inherited deficiency of N-acetyl-alpha-D
      glucosaminidase (Naglu) activity, an enzyme required to degrade the
      glycosaminoglycan heparan sulfate (HS). A deficiency in Naglu activity leads to
      lysosomal accumulation of HS as a primary storage substrate, and the gangliosides
      GM2 and GM3 as secondary accumulation products. To test the effect on
      neuropathogenesis of ganglioside accumulation, we bred mice deficient in both
      Naglu and GalNaAcT activities. The latter is the enzyme required for synthesis of
      GM2 and other complex gangliosides. Contrary to our expectation and to double
      knockout (DKO) studies where GalNAcT was knocked out in combination with other
      LSDs, our DKO mice showed a drastically shortened lifespan (24.5+/-1.4 weeks,
      versus 50.5+/-0.9 weeks (MPS IIIB), and 38.6+/-1.2 weeks (GalNAcT)). To confirm
      that HS storage was the primary element resulting in the accelerated disease in
      our DKO mice, and not a locus tightly linked to the Naglu gene, we replicated our
      study with MPS IIIA mice, and found a virtually identical result (27.5+/-1.8
      weeks, versus 53.8+/-1.6 weeks). All DKO mice showed motor signs of hind limb
      ataxia and hyper-extension, which were not seen in single KO or normal mice. At
      approximately 5 months of age, the MPS IIIB-DKO showed a unique pattern of
      vacuolization and nerve fiber degeneration in the corpus callosum, seen only in
      the DKO mice, as well as the relatively early intracytoplasmic vacuolation of
      many neurons and glia characteristic of the MPS IIIB mice. We analyzed motor
      performance on a rocking Rota-Rod beginning at 3 months of age. The MPS IIIA-DKO
      and MPS IIIB-DKO mice showed impaired performance and were statistically
      different from all parental lines. In particular, the MPS IIIB-DKO mice were
      significantly different from the parent MPS IIIB strains at 3, 5, and 6 months
      (p<=0.0245). In conclusion we identified an accelerated phenotype associated with
      MPS IIIB within a DKO model system which showed white matter changes, with
      attendant performance deficits and a drastically shortened lifespan. This was in
      stark contrast to our expectations of a salutary response to the elimination of
      GM2. Despite this, the accelerated pathology and clinical signs represent a
      potentially improved system to study MPS IIIB neuropathogenesis as well as the
      role of complex gangliosides in normal CNS function.

PMID- 22867888
TI  - The importance of "what": infants use featural information to index events.
AB  - Dynamic spatial indexing is the ability to encode, remember, and track the
      location of complex events. For example, in a previous study, 6-month-old infants
      were familiarized to a toy making a particular sound in a particular location,
      and later they fixated that empty location when they heard the sound presented
      alone (Journal of Experimental Psychology: General, 2004, Vol. 133, pp. 46-62).
      The basis and developmental trajectory of this ability are currently unclear. We
      investigated dynamic spatial indexing across the first year after birth and
      tested the hypothesis that the structure of visual cues supports infants'
      learning of sound and location associations. In our study, 3-, 6-, and 10-month
      olds were tested in a dynamic spatial indexing eye movement paradigm that paired
      two sounds with two locations. In one condition, these were reliably paired with
      two sets of visual features (two toys condition), replicating the original
      studies. We also presented a single set of visual cues in both locations (one toy
      condition) and multiple sets of visual features in both locations (six toys
      condition). Infants from 3 months of age onward showed evidence of dynamic
      spatial indexing in the two toys condition, but only the 10-month-olds succeeded
      in the one toy and six toys conditions. We argue that this may reflect a broader
      developmental trajectory, whereby infants first make use of multiple cue
      integration but with age are able to learn from a narrow set of cues.

PMID- 22867889
TI  - Fractures of the sacrum after chemoradiation for rectal carcinoma: incidence,
      risk factors, and radiographic evaluation.
AB  - PURPOSE: Sacral insufficiency fractures after adjuvant radiation for rectal
      carcinoma can present similarly to recurrent disease. As a complication
      associated with pelvic radiation, it is important to be aware of the incidence
      and risk factors associated with sacral fractures in the clinical assessment of
      these patients. METHODS AND MATERIALS: Between 1998 and 2007, a total of 582
      patients with locally advanced rectal carcinoma received adjuvant chemoradiation
      and surgical excision. Of these, 492 patients had imaging studies available for
      review. Hospital records and imaging studies from all 492 patients were
      retrospectively evaluated to identify risk factors associated with developing a
      sacral insufficiency fracture. RESULTS: With a median follow-up time of 3.5
      years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral
      fracture free rate was 0.91. Univariate analysis showed that increasing age (>=60
      vs. <60 years), female sex, and history of osteoporosis were significantly
      associated with shorter time to sacral fracture (P=.01, P=.004, P=.001,
      respectively). There was no significant difference in the time to sacral fracture
      for patients based on stage, radiotherapy dose, or chemotherapy regimen.
      Multivariate analysis showed increasing age (>=60 vs. <60 years, hazard ratio
      [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR =
      2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23
      8.50, P=.02) were independent risk factors associated with sacral fracture.
      CONCLUSIONS: Sacral insufficiency fractures after pelvic radiation for rectal
      carcinoma occur more commonly than previously described. Independent risk factors
      associated with fracture were osteoporosis, female sex, and age greater than 60
      years.

PMID- 22867890
TI  - Fully automated simultaneous integrated boosted-intensity modulated radiation
      therapy treatment planning is feasible for head-and-neck cancer: a prospective
      clinical study.
AB  - PURPOSE: To prospectively determine whether overlap volume histogram (OVH)
      driven, automated simultaneous integrated boosted (SIB)-intensity-modulated
      radiation therapy (IMRT) treatment planning for head-and-neck cancer can be
      implemented in clinics. METHODS AND MATERIALS: A prospective study was designed
      to compare fully automated plans (APs) created by an OVH-driven, automated
      planning application with clinical plans (CPs) created by dosimetrists in a 3
      dose-level (70 Gy, 63 Gy, and 58.1 Gy), head-and-neck SIB-IMRT planning. Because
      primary organ sparing (cord, brain, brainstem, mandible, and optic nerve/chiasm)
      always received the highest priority in clinical planning, the study aimed to
      show the noninferiority of APs with respect to PTV coverage and secondary organ
      sparing (parotid, brachial plexus, esophagus, larynx, inner ear, and oral
      mucosa). The sample size was determined a priori by a superiority hypothesis test
      that had 85% power to detect a 4% dose decrease in secondary organ sparing with a
      2-sided alpha level of 0.05. A generalized estimating equation (GEE) regression
      model was used for statistical comparison. RESULTS: Forty consecutive patients
      were accrued from July to December 2010. GEE analysis indicated that in APs,
      overall average dose to the secondary organs was reduced by 1.16 (95% CI = 0.09
      2.33) with P=.04, overall average PTV coverage was increased by 0.26% (95% CI =
      0.06-0.47) with P=.02 and overall average dose to the primary organs was reduced
      by 1.14 Gy (95% CI = 0.45-1.8) with P=.004. A physician determined that all APs
      could be delivered to patients, and APs were clinically superior in 27 of 40
      cases. CONCLUSIONS: The application can be implemented in clinics as a fast,
      reliable, and consistent way of generating plans that need only minor adjustments
      to meet specific clinical needs.

PMID- 22867892
TI  - The impact of the size of nodal metastases on recurrence risk in breast cancer
      patients with 1-3 positive axillary nodes after mastectomy.
AB  - PURPOSE: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients
      with 1-3 positive nodes is controversial. The objective of this study was to
      determine whether the size of nodal metastases in this subset could predict who
      would benefit from PMRT. METHODS AND MATERIALS: We analyzed 250 breast cancer
      patients with 1-3 positive nodes after mastectomy treated with contemporary
      surgery and systemic therapy at our institution. Of these patients, 204 did not
      receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were
      stratified by the size of the largest nodal metastasis measured as less than or
      equal to 5 mm or greater than 5 mm. RESULTS: The median follow-up was 65.6
      months. In the whole group, regional recurrences occurred in 2% of patients in
      whom the largest nodal metastasis measured 5 mm or less vs 6% for those with
      metastases measuring greater than 5 mm. For non-irradiated patients only,
      regional recurrence rates were 2% and 9%, respectively. Those with a maximal
      nodal size greater than 5 mm had a significantly higher cumulative incidence of
      regional recurrence (P=.013). The 5-year cumulative incidence of a regional
      recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI],
      0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%)
      for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for
      metastasis size greater than 10 mm. The impact of the maximal nodal size on
      regional recurrences became insignificant in the multivariable model.
      CONCLUSIONS: In patients with 1-3 positive lymph nodes undergoing mastectomy
      without radiation, nodal metastasis greater than 5 mm was associated with
      regional recurrence after mastectomy, but its effect was modified by other
      factors (such as tumor stage). The size of the largest nodal metastasis may be
      useful to identify high-risk patients who may benefit from radiation therapy
      after mastectomy.

PMID- 22867891
TI  - Short hairpin RNA suppression of thymidylate synthase produces DNA mismatches and
      results in excellent radiosensitization.
AB  - PURPOSE: To determine the effect of short hairpin ribonucleic acid (shRNA)
      mediated suppression of thymidylate synthase (TS) on cytotoxicity and
      radiosensitization and the mechanism by which these events occur. METHODS AND
      MATERIALS: shRNA suppression of TS was compared with 5-fluoro-2'-deoxyuridine
      (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29
      colon cancer cells. Cytotoxicity and radiosensitization were measured by
      clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects
      of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate
      imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid
      (DNA) were analyzed by high-pressure liquid chromatography and as pSP189 plasmid
      mutations, respectively. RESULTS: TS shRNA produced profound (>= 90%) and
      prolonged (>= 8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd
      increased TS expression. TS shRNA also produced more specific and prolonged
      effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA
      suppression allowed accumulation of cells in S-phase, although its effects were
      not as long-lasting as those of FdUrd. Both treatments resulted in
      phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was
      equally effective as FdUrd in eliciting radiosensitization (radiation enhancement
      ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar
      increase in the number and type of pSP189 mutations. CONCLUSIONS: TS shRNA
      produced less cytotoxicity than FdUrd but was equally effective at
      radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is
      sufficient to elicit radiosensitization with FdUrd, but it only partially
      explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in
      DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for
      the depletion of dTTP thymidine triphosphate and consequent DNA mismatches
      underlying radiosensitization. Importantly, shRNA suppression of TS avoids FP
      mediated TS elevation and its negative prognostic role. These studies support the
      further exploration of TS suppression as a novel radiosensitizing strategy.

PMID- 22867893
TI  - The role of postoperative radiation therapy in the treatment of meningeal
      hemangiopericytoma-experience from the SEER database.
AB  - PURPOSE: The aim of this study was to examine the effect of postoperative
      radiation therapy (RT) on cause-specific survival in patients with meningeal
      hemangiopericytomas. METHODS AND MATERIALS: The Surveillance, Epidemiology, and
      End Results database from 1990-2008 was queried for cases of surgically resected
      central nervous system hemangiopericytoma. Patient demographics, tumor location,
      and extent of resection were included in the analysis as covariates. The Kaplan
      Meier product-limit method was used to analyze cause-specific survival. A Cox
      proportional hazards regression analysis was conducted to determine which factors
      were associated with cause-specific survival. RESULTS: The mean follow-up time is
      7.9 years (95 months). There were 76 patients included in the analysis, of these,
      38 (50%) underwent gross total resection (GTR), whereas the other half underwent
      subtotal resection (STR). Postoperative RT was administered to 42% (16/38) of the
      patients in the GTR group and 50% (19/38) in the STR group. The 1-year, 10-year,
      and 20-year cause-specific survival rates were 99%, 75%, and 43%, respectively.
      On multivariate analysis, postoperative RT was associated with significantly
      better survival (HR = 0.269, 95% CI 0.084-0.862; P=.027), in particular for
      patients who underwent STR (HR = 0.088, 95% CI: 0.015-0.528; P<.008).
      CONCLUSIONS: In the absence of large prospective trials, the current clinical
      decision-making of hemangiopericytoma is mostly based on retrospective data. We
      recommend that postoperative RT be considered after subtotal resection for
      patients who could tolerate it. Based on the current literature, the practical
      approach is to deliver limited field RT to doses of 50-60 Gy while respecting the
      normal tissue tolerance. Further investigations are clearly needed to determine
      the optimal therapeutic strategy.

PMID- 22867895
TI  - The effect of dose-volume parameters and interfraction interval on cosmetic
      outcome and toxicity after 3-dimensional conformal accelerated partial breast
      irradiation.
AB  - PURPOSE: To evaluate dose-volume parameters and the interfraction interval (IFI)
      as they relate to cosmetic outcome and normal tissue effects of 3-dimensional
      conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation
      (APBI). METHODS AND MATERIALS: Eighty patients were treated by the use of 3D-CRT
      to deliver APBI at our institutions from 2003-2010 in strict accordance with the
      specified dose-volume constraints outlined in the National Surgical Adjuvant
      Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP
      B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions
      delivered twice daily. Patients underwent follow-up with assessment for
      recurrence, late toxicity, and overall cosmetic outcome. Tests for association
      between toxicity endpoints and dosimetric parameters were performed with the chi
      square test. Univariate logistic regression was used to evaluate the association
      of interfraction interval (IFI) with these outcomes. RESULTS: At a median follow
      up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in
      31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5
      patients (6%) with extended follow-up. Fat necrosis developed in 11% of women,
      and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue
      receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was
      associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%,
      and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9
      hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were
      not significantly associated with late toxicity. CONCLUSIONS: The incidence of
      moderate to severe late toxicity, particularly subcutaneous fibrosis and fat
      necrosis and resulting fair/poor cosmesis, remains high with continued follow-up.
      These toxicity endpoints are associated with several dose-volume parameters.
      Minimum and mean IFI values were not associated with late toxicity.

PMID- 22867894
TI  - Propensity score-based comparison of long-term outcomes with 3-dimensional
      conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer.
AB  - PURPOSE: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide
      standard for the treatment of esophageal cancer, intensity modulated radiotherapy
      (IMRT) improves dose conformality and reduces the radiation exposure to normal
      tissues. We hypothesized that the dosimetric advantages of IMRT should translate
      to substantive benefits in clinical outcomes compared with 3D-CRT. METHODS AND
      MATERIALS: An analysis was performed of 676 nonrandomized patients (3D-CRT,
      n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002)
      esophageal cancers treated with chemoradiotherapy at a single institution from
      1998-2008. An inverse probability of treatment weighting and inclusion of
      propensity score (treatment probability) as a covariate were used to compare
      overall survival time, interval to local failure, and interval to distant
      metastasis, while accounting for the effects of other clinically relevant
      covariates. The propensity scores were estimated using logistic regression
      analysis. RESULTS: A fitted multivariate inverse probability weighted-adjusted
      Cox model showed that the overall survival time was significantly associated with
      several well-known prognostic factors, along with the treatment modality (IMRT vs
      3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a
      significantly greater risk of dying (72.6% vs 52.9%, inverse probability of
      treatment weighting, log-rank test, P<.0001) and of locoregional recurrence
      (P=.0038). No difference was seen in cancer-specific mortality (Gray's test,
      P=.86) or distant metastasis (P=.99) between the 2 groups. An increased
      cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but
      most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT
      group, Gray's test, P=.0029). CONCLUSIONS: Overall survival, locoregional
      control, and noncancer-related death were significantly better after IMRT than
      after 3D-CRT. Although these results need confirmation, IMRT should be considered
      for the treatment of esophageal cancer.

PMID- 22867896
TI  - Statistical modeling of the eye for multimodal treatment planning for external
      beam radiation therapy of intraocular tumors.
AB  - PURPOSE: Ocular anatomy and radiation-associated toxicities provide unique
      challenges for external beam radiation therapy. For treatment planning, precise
      modeling of organs at risk and tumor volume are crucial. Development of a precise
      eye model and automatic adaptation of this model to patients' anatomy remain
      problematic because of organ shape variability. This work introduces the
      application of a 3-dimensional (3D) statistical shape model as a novel method for
      precise eye modeling for external beam radiation therapy of intraocular tumors.
      METHODS AND MATERIALS: Manual and automatic segmentations were compared for 17
      patients, based on head computed tomography (CT) volume scans. A 3D statistical
      shape model of the cornea, lens, and sclera as well as of the optic disc position
      was developed. Furthermore, an active shape model was built to enable automatic
      fitting of the eye model to CT slice stacks. Cross-validation was performed based
      on leave-one-out tests for all training shapes by measuring dice coefficients and
      mean segmentation errors between automatic segmentation and manual segmentation
      by an expert. RESULTS: Cross-validation revealed a dice similarity of 95%+/-2%
      for the sclera and cornea and 91%+/-2% for the lens. Overall, mean segmentation
      error was found to be 0.3+/-0.1 mm. Average segmentation time was 14+/-2 s on a
      standard personal computer. CONCLUSIONS: Our results show that the solution
      presented outperforms state-of-the-art methods in terms of accuracy, reliability,
      and robustness. Moreover, the eye model shape as well as its variability is
      learned from a training set rather than by making shape assumptions (eg, as with
      the spherical or elliptical model). Therefore, the model appears to be capable of
      modeling nonspherically and nonelliptically shaped eyes.

PMID- 22867897
TI  - Learning and memory following conformal radiation therapy for pediatric
      craniopharyngioma and low-grade glioma.
AB  - PURPOSE: The primary objective of this study was to examine whether children with
      low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory
      after conformal radiation therapy (CRT). A secondary objective was to determine
      whether children who received chemotherapy before CRT, a treatment often used to
      delay radiation therapy in younger children with LGG, received any protective
      benefit with respect to learning. METHODS AND MATERIALS: Learning and memory in
      57 children with LGG and 44 children with craniopharyngioma were assessed with
      the California Verbal Learning Test-Children's Version and the Visual-Auditory
      Learning tests. Learning measures were administered before CRT, 6 months later,
      and then yearly for a total of 5 years. RESULTS: No decline in learning scores
      after CRT was observed when patients were grouped by diagnosis. For children with
      LGG, chemotherapy before CRT did not provide a protective effect on learning.
      Multiple regression analyses, which accounted for age and tumor volume and
      location, found that children treated with chemotherapy before CRT were at
      greater risk of decline on learning measures than those treated with CRT alone.
      Variables predictive of learning and memory decline included hydrocephalus, shunt
      insertion, younger age at time of treatment, female gender, and pre-CRT
      chemotherapy. CONCLUSIONS: This study did not reveal any impairment or decline in
      learning after CRT in overall aggregate learning scores. However, several
      important variables were found to have a significant effect on neurocognitive
      outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on
      verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion
      in craniopharyngioma were found to be predictive of worse neurocognitive outcome,
      suggesting a more aggressive natural history for those patients.

PMID- 22867898
TI  - IGH@/BCL6 rearrangement on the der(3)t(3;14)(q27;q32) in primary mediastinal
      large B-cell lymphoma.

PMID- 22867899
TI  - Human immunodeficiency virus infection and chronic myeloid leukemia.
AB  - CML (chronic myeloid leukaemia) in association with HIV (human immunodeficiency
      virus) infection (HIV-CML) is rarely described and is likely to be coincidental.
      The natural history and behaviour of HIV-CML is different, being more atypical
      and aggressive. Both conditions, and their respective treatments may cause
      myelosuppression. Concurrent treatment with cART (combination antiretroviral
      therapy) and the tyrosine kinase inhibitors (TKI's) can result in appropriate
      control of CML and HIV infection, as well as long term survival. However, drug
      interactions between ARV's and TKI's may require adjustment of treatment.

PMID- 22867900
TI  - Outcome reporting for reconstructive breast surgery: the need for consensus,
      consistency and core outcome sets.

PMID- 22867901
TI  - Crosstalk between the ubiquitin-proteasome system and autophagy in a human
      cellular model of Alzheimer's disease.
AB  - Alzheimer's disease is the most common progressive neurodegenerative disorder
      characterized by the abnormal deposition of amyloid plaques, likely as a
      consequence of an incorrect processing of the amyloid-beta precursor protein
      (AbetaPP). Dysfunctions in both the ubiquitin-proteasome system and autophagy
      have also been observed. Recently, an extensive cross-talk between these two
      degradation pathways has emerged, but the exact implicated processes are yet to
      be clarified. In this work, we gained insight into such interplay by analyzing
      human SH-SY5Y neuroblastoma cells stably transfected either with wild-type
      AbetaPP gene or 717 valine-to-glycine AbetaPP-mutated gene. The over-expression
      of the AbetaPP mutant isoform correlates with an increase in oxidative stress and
      a remodeled pattern of protein degradation, with both marked inhibition of
      proteasome activities and impairment in the autophagic flux. To compensate for
      this altered scenario, cells try to promote the autophagy activation in a HDAC6
      dependent manner. The treatment with amyloid-beta(42) oligomers further
      compromises proteasome activity and also contributes to the inhibition of
      cathepsin-mediated proteolysis, finally favoring the neuronal degeneration and
      suggesting the existence of an Abeta(42) threshold level beyond which proteasome
      dependent proteolysis becomes definitely dysfunctional.

PMID- 22867902
TI  - Downregulation of A(1) and A(2B) adenosine receptors in human trisomy 21
      mesenchymal cells from first-trimester chorionic villi.
AB  - Human reproduction is complex and prone to failure. Though causes of miscarriage
      remain unclear, adenosine, a proangiogenic nucleoside, may help determine
      pregnancy outcome. Although adenosine receptor (AR) expression has been
      characterized in euploid pregnancies, no information is available for
      aneuploidies, which, as prone to spontaneous abortion (SA), are a potential model
      for shedding light on the mechanism regulating this event. AR expression was
      investigated in 71 first-trimester chorionic villi (CV) samples and cultured
      mesenchymal cells (MC) from euploid and TR21 pregnancies, one of the most
      frequent autosomal aneuploidy, with a view to elucidating their potential role in
      the modulation of vascular endothelial growth factor (VEGF) and nitric oxide
      (NO). Compared to euploid cells, reduced A(1) and A(2B) expression was revealed
      in TR21 CV and MCs. The non-selective adenosine agonist 5'-N
      ethylcarboxamidoadenosine (NECA) increased NO, by activating, predominantly,
      A(1)AR and A(2A)AR through a molecular pathway involving hypoxia-inducible-factor
      1 (HIF-1alpha), and increased VEGF, mainly through A(2B). In conclusion the
      adenosine transduction cascade appears to be disturbed in TR21 through reduced
      expression of A(2B) and A(1)ARs. These anomalies may be implicated in
      complications such as fetal growth restriction, malformation and/or SA, well
      known features of aneuploid pregnancies. Therefore A(1) and A(2B)ARs could be
      potential biomarkers able to provide an early indication of SA risk and their
      stimulation may turn out to improve fetoplacental perfusion by increasing NO and
      VEGF.

PMID- 22867903
TI  - RIKEN tandem mass spectral database (ReSpect) for phytochemicals: a plant
      specific MS/MS-based data resource and database.
AB  - The fragment pattern analysis of tandem mass spectrometry (MS/MS) has long been
      used for the structural characterization of metabolites. The construction of a
      plant-specific MS/MS data resource and database will enable complex phytochemical
      structures to be narrowed down to candidate structures. Therefore, a web-based
      database of MS/MS data pertaining to phytochemicals was developed and named
      ReSpect (RIKEN tandem mass spectral database). Of the 3595 metabolites in
      ReSpect, 76% were derived from 163 literature reports, whereas the rest was
      obtained from authentic standards. As a main web application of ReSpect, a
      fragment search was established based on only the m/z values of query data and
      records. The confidence levels of the annotations were managed using the MS/MS
      fragmentation association rule, which is an algorithm for discovering common
      fragmentations in MS/MS data. Using this data resource and database, a case study
      was conducted for the annotation of untargeted MS/MS data that were selected
      after quantitative trait locus analysis of the accessions (Gifu and Miyakojima)
      of a model legume Lotus japonicus. In the case study, unknown metabolites were
      successfully narrowed down to putative structures in the website.

PMID- 22867904
TI  - Co-occurrence of phenylphenalenones and flavonoids in Xiphidium caeruleum Aubl.
      flowers.
AB  - A Xiphidium caeruleum flower extract was separated by semi-preparative HPLC into
      five fractions, from which three flavonoids, two phenylphenalenones and 17
      phenylphenalenone-related compounds including five unknown compounds, were
      isolated and their structures elucidated by Liquid Chromatography-Diode Array
      Detection-Solid Phase Extraction-Nuclear Magnetic Resonance spectroscopy (LC-DAD
      SPE-NMR) and mass spectrometry (MS). This is the first report of the co
      occurrence of phenylphenalenones and flavonoids in the Haemodoraceae family. The
      ecological implications of flavonoids and various phenylphenalenone-type
      compounds and their putative biosynthesis sites in X. caeruleum are subject to
      discussion.

PMID- 22867905
TI  - Exploring the endocrine manifestations of DICER1 mutations.
AB  - The discovery of each new cancer susceptibility gene answers one set of questions
      but poses many more. In this article, we outline a recent example: a new cancer
      syndrome caused by germline mutations in DICER1, responsible for microRNA
      processing. In particular, we discuss the endocrine manifestations of mutations
      in this crucial gene.

PMID- 22867906
TI  - Studies of the effect of maltose on the direct binding of porcine pancreatic
      alpha-amylase to maize starch.
AB  - For a two phase system comprising an enzyme in solution acting on an insoluble
      substrate such as starch, adsorption of the enzyme is a key initial step in the
      reaction but few studies of agents affecting direct binding have been performed.
      The effect of maltose on the interaction of maize starch with porcine pancreatic
      alpha-amylase was studied by using a method in which the direct binding of starch
      to amylase is measured under conditions of negligible catalytic activity. The
      dissociation constant for starch binding increased with maltose concentration and
      analysis of the binding showed that the kinetic action of maltose was entirely
      competitive. This result accords with results described in the literature in
      which maltose was shown to be a competitive inhibitor of amylase action. If the
      maltose concentration is sufficiently high, a second molecule may bind at the
      active site but the affinity of the second binding step is approximately 6.5-fold
      weaker. Because of the relatively low affinity for maltose, it seems unlikely
      that inhibition by maltose of the initial stage of starch-amylase interaction
      normally plays any role in regulating intestinal digestion of starch.

PMID- 22867907
TI  - Synergistic mechanisms involved in the antidepressant effects of agomelatine.
AB  - Agomelatine is a novel and clinically effective antidepressant drug with
      melatonergic (MT1/MT2) agonist and 5-HT(2C) receptor antagonist properties. Both
      receptorial components are widely expressed in the central nervous system and it
      seems that this compound could act synergistically on both the melatonergic and
      the 5-HT(2C) receptors. In this review we will briefly summarize the preclinical
      evidence suggesting that the molecular-cellular effects of agomelatine and in
      turn its antidepressant activity are the result of a synergistic action between
      its agonism at MT1/MT2 and antagonism at 5-HT(2C) receptors. The antidepressant
      properties of agomelatine related to its effect on neurogenesis, cell survival,
      brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeleton
      associated protein (Arc) and stress-induced glutamate release, appear to be due
      to this synergistic action. Compared with traditional antidepressants which also
      affect these parameters, agomelatine is the only one able to resynchronize these
      effectors at distinct levels, circuital and intracellular. This suggests that
      agomelatine effects in restoring circadian rhythms and relieving depressive
      symptoms result from a synergistic interaction between melatonergic and
      serotonergic receptors.

PMID- 22867908
TI  - [Type 1b pseudohyperparathyroidism: a rare cause of syncope].

PMID- 22867909
TI  - Using plate mapping to examine sensitivity to plate size in food portions and
      meal composition among college students.
AB  - People eat meals rather than nutrients or food groups. Plate size may influence
      meal size, meal composition, and food type. To examine effects of plate size on
      meals, we developed a method we label plate mapping. A quasi-experimental study
      asked university students to accurately draw what they would like to eat for
      dinner on either a 9" or 11" paper plate. Coding plate drawings for total meal
      size revealed that students drew an average of 26% more food on larger plates.
      When plates were coded for meal composition we found that the biggest three food
      portions drawn by students were bigger on 11" plates, with 70% of the overall
      difference in food area occurring in the biggest food. Participants drew bigger
      portions of vegetables on larger plates, while other food types showed little
      change in mean size. Gender moderated plate sensitivity for food types: women
      drew 36% bigger vegetable portions than men on larger plates. Smaller plates may
      lead to smaller meal sizes, but plate size may differentially influence
      composition of meals for men and women. These findings suggest plate mapping can
      be used to reflect meal conceptualizations and assess sensitivity to plate size.

PMID- 22867910
TI  - Intra-household use and acceptability of Ready-to-Use-Supplementary-Foods
      distributed in Niger between July and December 2010.
AB  - Few studies have looked at consumption of Ready-to-Use-Supplementary-Foods
      (RUSFs) during a nutritional emergency. Here, we describe the use and
      acceptability of RUSF within households in four districts of the region of
      Maradi, Niger during large scale preventive distributions with RUSF in 2010
      targeted at children 6-35months of age. Our study comprised both quantitative and
      qualitative components to collect detailed information and to allow in-depth
      interviews. We performed a cross-sectional survey in 16 villages between two
      monthly distributions of RUSF (October-November 2010). All households with at
      least one child who received RUSF were included and a total of 1842 caregivers
      were interviewed using a structured questionnaire. Focus groups and individual
      interviews of 128 caregivers were conducted in eight of the selected villages. On
      average, 24.7% of households reported any sharing of RUSF within the household.
      Sharing practices outside the household remained rare. Most of the sharing
      reported occurred among children under 5years of age living in the household. On
      average, 91% of caregivers in all districts rated the child's appreciation of the
      products as good or very good. Program planning may need to explicitly accounting
      for the sharing of products among children under 5 within household.

PMID- 22867911
TI  - [Preoxygenation in obese patient with non-invasive pressure support ventilation:
      keep the pressure!].

PMID- 22867914
TI  - Acute skin failure.

PMID- 22867913
TI  - Physiotherapy intervention in Parkinson's disease: systematic review and meta
      analysis.
AB  - OBJECTIVE: To assess the effectiveness of physiotherapy compared with no
      intervention in patients with Parkinson's disease. DESIGN: Systematic review and
      meta-analysis of randomised controlled trials. DATA SOURCES: Literature
      databases, trial registries, journals, abstract books, and conference
      proceedings, and reference lists, searched up to the end of January 2012. REVIEW
      METHODS: Randomised controlled trials comparing physiotherapy with no
      intervention in patients with Parkinson's disease were eligible. Two authors
      independently abstracted data from each trial. Standard meta-analysis methods
      were used to assess the effectiveness of physiotherapy compared with no
      intervention. Tests for heterogeneity were used to assess for differences in
      treatment effect across different physiotherapy interventions used. Outcome
      measures were gait, functional mobility and balance, falls, clinician rated
      impairment and disability measures, patient rated quality of life, adverse
      events, compliance, and economic analysis outcomes. RESULTS: 39 trials of 1827
      participants met the inclusion criteria, of which 29 trials provided data for the
      meta-analyses. Significant benefit from physiotherapy was reported for nine of 18
      outcomes assessed. Outcomes which may be clinically significant were speed (0.04
      m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71
      points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease
      rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of
      daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30
      to -3.72, P<0.001). Indirect comparisons of the different physiotherapy
      interventions found no evidence that the treatment effect differed across the
      interventions for any outcomes assessed, apart from motor subscores on the
      unified Parkinson's disease rating scale (in which one trial was found to be the
      cause of the heterogeneity). CONCLUSIONS: Physiotherapy has short term benefits
      in Parkinson's disease. A wide range of physiotherapy techniques are currently
      used to treat Parkinson's disease, with little difference in treatment effects.
      Large, well designed, randomised controlled trials with improved methodology and
      reporting are needed to assess the efficacy and cost effectiveness of
      physiotherapy for treating Parkinson's disease in the longer term.

PMID- 22867915
TI  - Adverse events in children having surgery are common and need investigation,
      study concludes.

PMID- 22867916
TI  - One in three survivors of childhood meningitis is left with "hidden" after
      effects, study finds.

PMID- 22867917
TI  - Expert group advises separating risk and benefit information from cancer
      screening invitations.

PMID- 22867918
TI  - Texas judge throws out Wakefield's libel action against BMJ.

PMID- 22867919
TI  - [Pleomorphic xanthoastrocytoma with intraventricular extension and anaplastic
      transformation in an adult patient: Case report].
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumour that
      usually occurs in the superficial cerebral hemispheres of children and young
      adults. Although it has a relatively favourable prognosis, malignant progression
      of these tumours has been described. Therefore, we present an unusual case of a
      54-year-old male with a right, multicystic, parietooccipital tumour extending
      through the ipsilateral ventricle. After surgical resection, histological
      examination revealed a lesion with pleomorphic cells, cytoplasmic lipidisation,
      intensely eosinophilic granular bodies, well-delimitated unique nuclei and focal,
      positive immunoreactivity for synaptophysin, glial fibrillary acidic protein
      (GFAP), S-100 protein, vimentin and CD56. Once other tumours, such as giant cell
      metastatic carcinoma or primary lesion like subependymal giant cell astrocytoma,
      were ruled out, a final diagnosis of XAP was established. After a follow-up
      period of 9 months, the patient suffered an extensive and local tumour relapse
      considered inoperable, with progressive neurological deterioration and
      radiological findings of malignant progression. The brain biopsy procedure
      revealed anaplastic changes, including necrosis foci, higher mitotic activity
      (5*10 high-power fields) and a 10% proliferation index measured by Ki67
      labelling. The present case showed intraventricular extension and a more
      aggressive behaviour, both uncommon in these tumours (similar to anaplastic
      astrocytoma or glioblastoma multiforme), thus demanding an initial, optimal
      surgical treatment with close clinical and radiological follow-up, due to the
      high potential for malignant transformation of XAPs.

PMID- 22867920
TI  - Lymphatic mapping/sentinel lymphadenectomy.

PMID- 22867921
TI  - Breast cancer. Introduction.

PMID- 22867922
TI  - Axillary anatomy and history.

PMID- 22867923
TI  - Nonsurgical adjunctive treatment and its effects on the axilla.

PMID- 22867924
TI  - [High resolution (3 T) magnetic resonance neurography of the sciatic nerve].
AB  - Magnetic resonance (MR) neurography refers to a set of techniques that enable the
      structure of the peripheral nerves and nerve plexuses to be evaluated optimally.
      New two-dimensional and three-dimensional neurographic sequences, in particular
      in 3T scanners, achieve excellent contrast between the nerve and perineural
      structures. MR neurography makes it possible to distinguish between the normal
      fascicular pattern of the nerve and anomalies like inflammation, trauma, and
      tumor that can affect nerves. In this article, we describe the structure of the
      sciatic nerve, its characteristics on MR neurography, and the most common
      diseases that affect it.

PMID- 22867925
TI  - [Velocity of diametric expansion for high-grade gliomas].

PMID- 22867926
TI  - Musculoskeletal conditions. Preface.

PMID- 22867927
TI  - Lifestyle- and behaviour-change interventions in musculoskeletal conditions.
AB  - This review discusses several health behaviours associated with the progression
      and impact of osteoarthritis (OA) and rheumatoid arthritis (RA), including weight
      management, physical activity, medication adherence and smoking. An overview of
      current theories of behaviour-change is provided in terms of principles that can
      guide medical practice. Finally, evaluation studies of interventions targeting
      weight loss, physical activity and medication adherence in patients with OA or RA
      are presented and discussed. Of existing behaviour-change interventions in this
      population, few have taken a comprehensive theory-based approach to behaviour
      change. Practitioners who provide lifestyle or behavioural advice to patients
      would do well to adopt a less prescriptive and more patient-centred approach in
      which they, or other health professionals to whom they refer the patient, assist
      the patient in formulating personal change goals, in translating good intentions
      into specific action plans and in closely monitoring their progress towards self
      chosen goals.

PMID- 22867928
TI  - Psychological interventions for patients with rheumatic diseases and anxiety or
      depression.
AB  - The prevalence of clinical anxiety and clinical depression in rheumatic diseases
      is about twice the prevalence seen in the general population. At a milder level,
      the occurrence of psychological distress that does not fulfil diagnostic criteria
      of anxiety and depression is even higher. Evidence indicates that this high
      prevalence is multifactorial. Correlational studies suggest that possible factors
      for anxiety and depression include the suffering accompanying somatic symptoms,
      functional limitations, pro-inflammatory cytokines, helplessness due to the
      uncontrollable, unpredictable and progressive nature of the disease, and other
      factors associated with having a chronic disease. This article reviews the
      prevalence and diagnosis of anxiety and depression in rheumatic diseases and it
      examines the contents and the impact of psychological interventions to address
      these difficulties for patients.

PMID- 22867929
TI  - Self-management interventions in the digital age: new approaches to support
      people with rheumatologic conditions.
AB  - Self-management interventions are considered a key component of rheumatologic
      care. Access to these programmes, however, is an issue for some patients,
      especially those working full time or living in rural and remote communities.
      Recently, there has been an increase in the use of digital media technologies to
      deliver self-management interventions. Digital media (e.g., websites, mobile
      applications, social networking tools, online games and animation) provide
      tremendous flexibility for delivering health information and resources at a time
      and place that is chosen by the individual; hence, they are consistent with the
      patient-centred approach. This review discusses: (1) innovations in self
      management interventions for patients with arthritis and (2) research in the use
      of digital media for delivering self-management interventions.

PMID- 22867930
TI  - Aquatic exercise & balneotherapy in musculoskeletal conditions.
AB  - This is a best-evidence synthesis providing an evidence-based summary on the
      effectiveness of aquatic exercises and balneotherapy in the treatment of
      musculoskeletal conditions. The most prevalent musculoskeletal conditions
      addressed in this review include: low back pain, osteoarthritis, fibromyalgia and
      rheumatoid arthritis. Over 30 years of research demonstrates that exercises in
      general, and specifically aquatic exercises, are beneficial for reducing pain and
      disability in many musculoskeletal conditions demonstrating small to moderate
      effect sizes ranging between 0.19 and 0.32. Balneotherapy might be beneficial,
      but the evidence is yet insufficient to make a definitive statement about its
      use. High-quality trials are needed on balneotherapy and aquatic exercises
      research especially in specific patient categories that might benefit most.

PMID- 22867932
TI  - Management of work disability in rheumatic conditions: a review of non
      pharmacological interventions.
AB  - Because of its substantial personal social and economic costs, workforce
      participation among individuals with rheumatic diseases has received considerable
      research attention. This chapter reviews non-pharmacological employment
      interventions for people with rheumatic diseases, focussing on the
      comprehensiveness of interventions, whether they have been targeted to those
      groups identified as most at risk, and intervention outcomes and effectiveness.
      Findings highlight that early diagnosis and treatment of rheumatic diseases may
      not be enough to keep individuals employed and that comprehensive work
      interventions may have positive psychological effects, as well as result in
      increased work participation. However, we lack data addressing the optimum time
      to intervene and subgroup analyses to determine whether some groups are at
      increased risk for poor work outcomes. Consistent inclusion of behavioural and
      psychological outcomes to evaluate interventions and compare studies is also
      needed, along with cost-benefit studies, to determine the long-term feasibility
      of work interventions.

PMID- 22867933
TI  - Tai Chi and yoga as complementary therapies in rheumatologic conditions.
AB  - Tai Chi and yoga are complementary therapies which have, during the last few
      decades, emerged as popular treatments for rheumatologic and musculoskeletal
      diseases. This review covers the evidence of Tai Chi and yoga in the management
      of rheumatologic diseases, especially osteoarthritis of the knee, hip and hand,
      and rheumatoid arthritis. There is evidence that Tai Chi and yoga are safe, and
      some evidence that they have benefit, leading to reduction of pain and
      improvement of physical function and quality of life in patients. Recommendations
      for Tai Chi in knee osteoarthritis have recently been issued by the American
      College of Rheumatology. To allow broader recommendations for the use of Tai Chi
      and yoga in rheumatic diseases, there is a need to collect more evidence
      researched with larger randomised controlled trials.

PMID- 22867934
TI  - The role of patient organisations in musculoskeletal care.
AB  - Better integration of patient organisations with health-care has been called for
      in policy statements by for example, the World Health Organization. Our aim was
      to describe the role of patient organisations in musculoskeletal care. We suggest
      that their work could be divided into three different fields of activities, that
      is, member benefits to satisfy individual needs, raised awareness to create
      better conditions for people with disability and the promotion of research to
      improve prevention, care and find a definite cure. Some scientific work exists to
      support that people with musculoskeletal conditions perceive a delay in
      information about patient organisations, that simple leaflets are effective in
      promoting such contacts and that they result in improved health behaviours.
      Furthermore, patient organisations may assist in improving health-care providers'
      education and skills training, and also support advocacy in political and
      societal issues with consequences for health-care practice. Mutual support and
      collaboration are thus encouraged.

PMID- 22867935
TI  - Gait deviations in individuals with inflammatory joint diseases and
      osteoarthritis and the usage of three-dimensional gait analysis.
AB  - This chapter describes three-dimensional gait analysis and common gait deviations
      in adults with rheumatoid arthritis (RA) and osteoarthritis (OA). Furthermore, we
      describe changes in gait deviations following surgical and non-surgical
      interventions. Gait analysis is used to define gait deviations and to evaluate
      varying surgical approaches, types of surgeries and non-pharmacologic
      interventions. Most studies examine gait in adults with knee OA. Limitations of
      existing studies include small samples, poor selection of controls, sample
      heterogenecity, lack of baseline gait assessments and inconsistency in
      measurement. Across studies, time and distance parameters are generally used to
      provide a global measure of gait deviations. Individuals with RA and OA in the
      lower extremities exhibit reduced walking speed/cadence and decreased motion and
      moments in relation to healthy subjects. Future research should include larger
      sample sizes, the use of proper controls, pre- and post-assessments and identify
      gait abnormalities early in the disease process to minimise long-term
      consequences.

PMID- 22867931
TI  - Musculoskeletal conditions of the foot and ankle: assessments and treatment
      options.
AB  - Musculoskeletal conditions of the foot and ankle are an important public health
      challenge due to their increasing incidence combined with their substantial
      negative impact on patients' quality of life. Non-pharmacological treatments
      serve as the first line of treatment and are frequently used for patients with
      musculoskeletal conditions of the foot and ankle. This review provides a summary
      of the assessments and non-invasive treatment options based upon available
      evidence. Recent studies show that individuals with foot and ankle pain have
      multiple co-existing impairments in alignment, motion, load distribution and
      muscle performance that may be evident in static and/or dynamic tasks. In
      addition, both clinical and epidemiological studies support the inter-dependence
      between the foot and proximal joints. For instance, aberrant foot structure has
      been linked to foot osteoarthritis (OA), as well as OA and pain at the knee and
      hip. Most recently, advances in motion capture technology and plantar load
      distribution measurement offer opportunities for precise dynamic assessments of
      the foot and ankle. In individuals with musculoskeletal conditions of the foot
      and ankle, the chief objectives of treatment are to afford pain relief, restore
      mechanics (alignment, motion and/or load distribution) and return the patient to
      their desired level of activity participation. Given that most patients present
      with multiple impairments, combinational therapies that target foot-specific as
      well as global impairments have shown promising results. In particular, in
      individuals with rheumatoid arthritis and other rheumatic diseases, comprehensive
      rehabilitation strategies including early detection, foot-based interventions
      (such as orthoses) and wellness-based approaches for physical activity and self
      management have been successful. While significant improvements have been made in
      the last decade to the assessment and treatment of foot and ankle conditions, few
      randomised clinical trials specifically have investigated patients with foot or
      ankle conditions to provide global insights into this area. Consequently, current
      recommendations vary based upon the scope of studies presented in this review as
      well as the strength of studies. This review indicates a need for more in-depth
      investigations into the components of assessment and treatment options for foot
      and ankle musculoskeletal conditions.

PMID- 22867936
TI  - The analgesic and anti-inflammatory effect of new oleanolic acid acyloxyimino
      derivative.
AB  - The new derivative of well-known triterpene, oleanolic acid: methyl 3
      octanoyloxyiminoolean-12-en-28-oate 5, was synthesized by the action of caprylic
      acid on methyl oleanolate 3-oxime in the presence of dicyclohexylcarbodiimide in
      dioxane. The molecular structure of the obtained product 5 was confirmed by
      spectral methods. The acute toxicity, locomotor activity, and the dose-dependent
      analgesic activity were studied. In addition, the effect of compound 5 on
      morphine-induced analgesic activity, the dose-dependent anti-inflammatory
      activity and the effect of the compound on diclofenac anti-inflammatory activity
      study were performed. The results proved a low toxicity (LD50 > 2 g/kg) of the
      tested product 5, which affected neither vertical nor horizontal locomotor
      activity in the given range of doses. The triterpene 5 also produced centrally
      mediated (morphine-like) analgesic action; however, only in the highest dose. The
      synergistic analgesic activity of 5 and morphine in the doses of 30.0 and
      300.0mg/kg was found. Compound 5 expressed the anti-inflammatory action which did
      not affect the anti-inflammatory activity of diclofenac after their combined
      administration.

PMID- 22867938
TI  - Effect of elastic energy on the folding of an RNA hairpin.
AB  - We analyse the folding and unfolding of an RNA hairpin using a conventional
      zipping model that includes both the free energy for RNA binding and the elastic
      free energy of the system. Unfolding under isotonic conditions (where we control
      the applied load) is known to occur at a well-defined critical load. In marked
      contrast, we find that unfolding under isometric conditions (where we control the
      extension of the hairpin) produces a series of sharp peaks in the average load as
      the stem of the hairpin starts to unzip base by base. A peak occurs when the
      elastic energy stored in the unzipped arms of the hairpin becomes so large that
      it is energetically favourable for the next base pair to unzip: the consequent
      increase in the contour length of the unzipped arms reduces their elastic energy
      and causes the average load to fall abruptly. However, as the contour length of
      the unzipped arms increases, the peaks become less distinct. Moreover, when we
      include the long DNA/RNA handles that have been used in single-molecule
      experiments, the unzipping of individual base pairs cannot be resolved at all.
      Instead, with the hairpin in the folded state, the average load increases with
      extension until the elastic energy stored in the handles makes it energetically
      favourable for the hairpin to unzip over a narrow range of extensions. The
      resultant yield point produces a mechanical hysteresis loop with a negative
      slope, as observed experimentally. Unfolding of the hairpin is also affected by
      the elastic energy stored in a compliant force transducer. We find that short,
      stiff handles and a stiff force transducer could improve the resolution of
      mechanical experiments on single molecules. 

PMID- 22867939
TI  - A systematic review of coverage decision-making on health technologies-evidence
      from the real world.
AB  - OBJECTIVE: Quantitative analysis of real-world coverage decision-making offers
      insights into the revealed preferences of appraisal committees. Aim of this
      review was to structure empirical evidence of coverage decisions made in practice
      based on the components 'methods and evidence', 'criteria and standards',
      'decision outcome' and 'processes'. METHODS: Several electronic databases, key
      journals and decision committees' websites were searched for publications between
      1993 and June 2011. Inclusion criteria were the analysis of past decisions and
      application of quantitative methods. Each study was categorized by the scope of
      decision-making and the components covered by the variables used in quantitative
      analysis. RESULTS: Thirty-two studies were identified. Many focused on
      pharmaceuticals, the UK NICE or the Australian PBAC. The components were covered
      comprehensively, but heterogeneously. Seventy-two variables were identified of
      which the following were more prevalent: specifications of the decision outcome;
      the indications considered for appraisal, identification of incremental cost
      effectiveness ratios, appropriateness of evaluation methods, type of economic or
      clinical evidence used for assessment, and the decision date. CONCLUSIONS:
      Research was dominated by analysis of decision outcomes and appraisal criteria.
      Although common approaches were identified, the complexity of coverage decision
      making - reflected by the heterogeneity of identified variables - will continue
      to challenge empirical research.

PMID- 22867940
TI  - Unexpected impact of changes in out-of-pocket payments for health care on Czech
      household budgets.
AB  - The Czech Republic is one of the countries that has a relatively low level of
      private spending on health. As a part of the health care reform package in 2008,
      some additional out-of-pocket payments were introduced, called 'user (patient)
      fees'. Furthermore, the government intends to increase some user fees in the
      following years. There have been serious discussions between proponents and
      opponents because an increase in out of pocket payments for health care may
      create financial obstacles for some households and restrict the desirable
      consumption of health care. The objective of this paper is to determine the
      impact of changes in out-of-pocket payments on household budgets and provide
      solution for more just distribution of the burden. Data from the household budget
      survey regularly collected by the Czech Statistical Office is used. Results
      showed that the burden of households increased from 2.15% of their net income to
      2.63% in 2008 and to 2.55% in 2009 after the implementation of user fees. We
      noted that the presence of pensioners and elderly in a household was the factor
      which increased the overall burden the most and led to catastrophic payments.

PMID- 22867941
TI  - Effects of the glucagon-like polypeptide-1 analogue (Val8)GLP-1 on learning,
      progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain.
AB  - Type 2 diabetes (T2DM) has been identified as a risk factor for Alzheimer's
      disease. Here, we tested the properties of the glucagon-like polypetide-1 (GLP-1)
      analogue (Val8)GLP-1, a drug originally developed as a treatment for T2DM at a
      range of doses (2.5 nmol; 25 nmol; 100 nmol; or 250 nmol/kg bw ip.) in an acute
      memory study in wild type C57B/l6 mice. We also tested (Val8)GLP-1 and the GLP-1
      receptor antagonist exendin (9-39) in a chronic study (3 weeks at 25 nmol/kg bw
      ip. once-daily). We found that (Val8)GLP-1 crossed the blood brain barrier
      readily and that peripheral injection increased levels in the brain 30 min post
      injection ip. but not 2h post-injection in rats. In the acute study, the low dose
      of 2.5 nmol/kg ip. enhanced motor activity in the open field task, while total
      distance travelled, exploratory behaviour and anxiety was not affected at any
      dose. Learning an object recognition task was not affected either. In the chronic
      study, no effect was observed in the open field assessment. The antagonist
      exendin (9-39) impaired object recognition learning and spatial learning in a
      water maze task, demonstrating the importance of GLP-1 signalling in memory
      formation. Locomotor activity was also affected in some cases. Blood sugar levels
      and insulin sensitivity was not affected in chronically treated mice. Neuronal
      stem cells and neurogenesis was enhanced by (Val8)GLP-1 in the dentate gyrus of
      wild type mice. The results demonstrate that (Val8)GLP-1 is safe in a range of
      doses, crosses the BBB and has potentially beneficial effects in the CNS by
      enhancing neurogenesis.

PMID- 22867943
TI  - Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and risk
      of appendicitis.
AB  - PURPOSE: Angiotensin-converting-enzyme (ACE) inhibitors and, less commonly,
      angiotensin-receptor blockers (ARBs), have been associated with angioedema,
      including small bowel angioedema. We sought to determine whether this process
      might be associated with appendicitis. METHODS: We conducted a nested case
      control study of incident appendicitis in a subcohort of 305,958 commercially
      insured hypertensive adults throughout the United States. Individuals with
      appendicitis were matched on age, sex, region, and subscriber status with up to
      10 controls, and we examined use of ACE inhibitors, ARBs, beta-blockers, calcium
      channel blockers, and thiazides in the previous 12 months. RESULTS: A total of
      576 cases of appendicitis were matched to 4808 control subjects. The risk of
      appendicitis appeared greater among users of ACE inhibitors and ARBs (adjusted
      hazard ratio 1.22; 95% confidence interval 0.98-1.52), but not other
      antihypertensive classes. Risk was not significantly different between ACE
      inhibitors and ARBs (P = .36). We found a graded increase in risk based upon
      filled prescriptions, with stepwise greater risk among individuals who filled
      <80% and >= 80% of doses in the preceding year (P trend .03). CONCLUSIONS: In
      this population of middle-aged Americans with hypertension, the use of ACE
      inhibitors or ARBs was associated with greater risk of appendicitis. These
      results suggest a possible previously unrecognized noncardiovascular side effect
      of these widespread classes of medication.

PMID- 22867942
TI  - Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia:
      inhibition of protein oxidation/nitration, 12/15-lipoxygenase and blood-brain
      barrier disruption.
AB  - Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow
      pigments, the aqueous extract of safflower florets. We report here an
      experimental study for evaluating HSYA for their neuroprotective qualities on
      rats subjected to middle cerebral artery occlusion (60 min) and reperfusion
      (24h), an experimental model in which excessive production of reactive oxygen and
      nitrogen species has been found. In our data, biochemical analysis of tissue
      proteins showed that cerebral ischemia/reperfusion (I/R) injury resulted in
      significant elevation of carbonyl groups and nitrotyrosine in the brain of I/R in
      comparison to sham controls, indicating the occurrence of oxidative/nitrative
      modification to brain proteins. HSYA-treatment (1, 5 and 10mg/kg) inhibited I/R
      induced protein oxidation and nitration. 12/15-Lipoxygenase (12/15-LOX), the
      enzyme implicated in oxidative stress of cerebral I/R, displayed overexpression
      in I/R rats. Elevated 12/15-LOX activity, estimated by the level of its
      metabolite 15-hydroxyeicosatetraenoic acid (15-HETE), was also induced by the
      challenge of cerebral I/R. Administration of HSYA 1, 5 and 10mg/kg reduced the
      upregulation of 12/15-LOX expression and activity in a dose-dependent manner.
      Moreover, the increase in blood-brain barrier (BBB) permeability evaluated by IgG
      leakage, Evans blue extravasation, and brain water content, respectively, was
      markedly alleviated by HSYA, indicating its protection against BBB disruption and
      brain edema following I/R insult. Taken together, these results demonstrate the
      neuroprotective properties of HSYA, which may be at least in part due to its
      potential to reduce protein oxidation and nitration, inhibit the upregulation of
      12/15-LOX, and attenuate BBB breakdown.

PMID- 22867944
TI  - An alternative form of melarsoprol in sleeping sickness: is an old drug always
      the best basis for a new one?

PMID- 22867946
TI  - Global gene expression and functional network analysis of gastric cancer identify
      extended pathway maps and GPRC5A as a potential biomarker.
AB  - To get more understanding of the molecular mechanisms underlying gastric cancer,
      25 paired samples were applied to gene expression microarray analysis. Here,
      expression microarray, quantitative reverse transcription-PCR (qRT-PCR) and
      immunohistochemical analysis indicated that GPRC5A was significantly elevated in
      gastric cancer tissues. The integrative network analysis of deregulated genes
      generated eight subnetworks. We also mapped copy number variations (CNVs) and
      associated mRNA expression changes into pathways and identified WNT, RTK-Ras-PI3K
      AKT, NF-kappaB, and PLAU-JAK-STAT pathways involved in proliferation, evading
      apoptosis and sustained angiogenesis, respectively. Taken together, our results
      reveal several interesting genes including GPRC5A as potential biomarkers for
      gastric cancer, and highlight more systematical insight of deregulated genes in
      genetic pathways of gastric carcinogenesis.

PMID- 22867945
TI  - Targeting Jab1/CSN5 in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated head and neck
      cancer that is most common in eastern Asia. Epstein-Barr virus infection,
      environmental factors, and genetic susceptibility play important roles in NPC
      pathogenesis. Jab1/CSN5 is a multifunctional protein that participates in
      affecting integrin signaling, controlling cell proliferation and apoptosis, and
      regulating genomic instability and DNA repair. Correlation of Jab1/CSN5
      overexpression with poor prognosis for NPC provides evidence that it is involved
      in the tumorigenic process. In this review, we highlight recent advances in
      studies of the oncogenic role of Jab1/CSN5 in NPC and its potential as a
      therapeutic target for this cancer.

PMID- 22867948
TI  - Predictors for the development of non-Hodgkin lymphoma in primary Sjogren's
      syndrome.
AB  - Sjogren's syndrome (SS) is a complex autoimmune disease with multi-organ
      involvement. Its most serious complication is the development of non-Hodgkin
      lymphoma (NHL). In cohorts of unselected patients with long observation, this
      lifetime risk is estimated to be 5 to 15%, or approximately 20 times increased
      risk compared to the general population. Being able to identify patients prone to
      malignancy would significantly aid in the process of customised treatment and
      strategy for follow-up. Among the established predictors for lymphoma development
      in SS, we recognize recurrent or permanent swelling of major salivary glands
      (SG), lymphadenopathy, cryoglobulinemia, splenomegaly, low complement levels of
      C4 and C3, lymphopenia, skin vasculitis or palpable purpura, M-component in serum
      or urine, peripheral neuropathy, glomerulonephritis and elevated beta2
      microglobulin. More recent suggestions include some genetic factors, CD4
      lymphocytopenia, and ectopic germinal center-like structures in minor SG
      biopsies. Despite these predictors, there remains a need for defining algorithms
      for NHL screening and patient follow-up in SS.

PMID- 22867947
TI  - Helicobacter pylori decreases p27 expression through the delta opioid receptor
      mediated inhibition of histone acetylation within the p27 promoter.
AB  - Chronic Helicobacter pylori infection is associated with the decreased expression
      of the gastric tumour suppressor protein p27. Because transcription of the gene
      p27 may be regulated epigenetically through histone acetylation, which is
      mediated by G-protein coupled delta opioid receptor (DOR) stimulation, we
      examined whether H. pylori regulates the DOR/histone acetylation/p27 promoter
      pathway. The levels of acetylated histone and p300, a gene-specific histone
      acetyltransferase within the p27 promoter, were measured using ChIP assays. The
      expression of phospho-DOR was evaluated by Western blot and immunohistochemical
      analyses. Growth curves were constructed, and cell proliferation was assessed
      after BrdU incorporation. Low p27 expression in acutely H. pylori-infected AGS
      gastric epithelial cells and in chronically H. pylori-infected AGS-derived HS3C
      cells was associated with approximate 20% and 40% decreases in p27 mRNA
      expression, respectively, when compared to p27 mRNA levels in uninfected AGS
      parental cells. The low p27 mRNA levels following H. pylori infection were
      associated with a 15-60% reduction in p27 promoter histone H4 acetylation. The
      recruitment of p300 to the p27 promoter was also markedly decreased by H. pylori
      infection. The expression of phospho-DOR was decreased by H. pylori infection in
      cell lines in vitro and in H. pylori-infected human gastric mucosa in vivo. The
      level of cellular p27 inversely correlated with cell proliferation in HS3C cells.
      These results demonstrate that H. pylori decreases p27 expression by modulating
      the DOR and thereby inhibiting histone acetylation of the p27 promoter. These
      findings link low gastric p27 expression levels with increased instances of
      gastric carcinogenesis associated with H. pylori infection.

PMID- 22867949
TI  - [Improvement in urinary tract infections rates in a department of internal
      medicine].
AB  - OBJECTIVE: To evaluate the impact on the urinary tract infections (UTI) rates of
      an intervention implemented in the Department of Internal Medicine of the
      Hospital Universitario Insular de Gran Canaria. MATERIAL AND METHODS: Infection
      control practitioners implemented a three phase project, each lasting two months,
      focusing on surveillance and feed-back, between 2009 and 2011. During phases 1
      and 2, the 2004 Centers for Disease Control and Prevention (CDC)-diagnostic
      criteria for nosocomial infections were followed, and only rates of infections
      were calculated. For phase 3, the criteria published in 2009 were used, and rates
      of infections plus processes rates were obtained. The cumulative incidence of UTI
      in the three periods was compared using a chi-square for trends test. RESULTS:
      The total number of catheter days, as well as the cumulative incidence of UTI
      dropped from phase 1 to 3. Nevertheless, in phase 2 the mean urinary catheter
      days increased. We detected a decrease in the UTI rates and urinary catheter days
      mean after introducing an electronic reminder in the patient electronic charts.
      CONCLUSIONS: A multidisciplinary approach, including surveillance, reminders, and
      feed-back, has proved useful in controlling UTI rates in our hospital.

PMID- 22867950
TI  - Should it matter when we record? Time of year and time of day as factors
      influencing frontal EEG asymmetry.
AB  - Resting frontal encephalographic (EEG) asymmetry, often conceptualized as a trait
      marker for depression, is influenced by occasion-specific factors, including time
      of year and the time of day of the recording session as demonstrated recently
      (Peterson and Harmon-Jones, 2009). The current study examined the influence of
      seasonal and chronological variables on resting frontal asymmetry, and also
      assessed whether different reference montages or surface transformations were
      equally susceptible to these influences. In a direct replication attempt,
      contrary to previous findings, no simple time of year by time of day interaction
      was found. Time awake at recording, however, was an important moderating variable
      of the relationship between photoperiod and time of day. EEG asymmetry scores
      based on current-source density (CSD) transformed data, however, appeared less
      vulnerable to these influences, providing further evidence to suggest that the
      CSD transform may be advantageous for examining stable trait estimates of frontal
      EEG asymmetry.

PMID- 22867951
TI  - Impact of family history and depression on amygdala volume.
AB  - Family history of depression significantly impacts life-long depression risk.
      Family history could impact the stress and emotion regulation system that
      involves the amygdala. This study's purpose was to investigate family history's
      effect on amygdala volumes, and differences in first degree relatives with and
      without major depressive disorder (MDD). Participants, aged 18-65, were healthy
      volunteers (N=52) with (n=26) and without (n=26) first degree family history, and
      patients with MDD (N=48) with (n=27) and without (n=21)first-degree family
      history recruited for structural magnetic resonance imaging (MRI). Participants
      underwent clinical assessment followed by manual amygdala tracing. Patients with
      MDD without family history showed significantly larger right amygdala compared to
      patients with a MDD family history.MDD without family history also had larger
      right amygdala than healthy controls without MDD family history.These effects
      were pronounced in females. Family history and gender impacted amygdala volumes
      in all participants providing rationale for the inconsistent results in MDD
      amygdala studies [corrected]. Higher familial risk in depression seems to be
      associated with smaller amygdala volumes, whereas depression alone is associated
      with larger amygdala volumes. Ultimately, these findings highlight consideration
      of family history and gender in research and treatment strategies.

PMID- 22867952
TI  - Hippocampus and nucleus accumbens activity during neutral word recognition
      related to trait physical anhedonia in patients with schizophrenia: an fMRI
      study.
AB  - Emotional memory dysfunction may be associated with anhedonia in schizophrenia.
      This study aimed to investigate the neurobiological basis of emotional memory and
      its relationship with anhedonia in schizophrenia specifically in emotional memory
      relate brain regions of interest (ROIs) including the amygdala, hippocampus,
      nucleus accumbens, and ventromedial prefrontal cortex. Fourteen patients with
      schizophrenia and 16 healthy subjects performed a word-image associative encoding
      task, during which a neutral word was presented with a positive, neutral, or
      control image. Subjects underwent functional magnetic resonance imaging while
      performing the recognition task. Correlation analyses were performed between the
      percent signal change (PSC) in the ROIs and the anhedonia scores. We found no
      group differences in recognition accuracy and reaction time. The PSC of the
      hippocampus in the positive and neutral conditions, and the PSC in the nucleus
      accumbens in the control condition, appeared to be negatively correlated with the
      Physical Anhedonia Scale (PAS) scores in patients with schizophrenia, while
      significant correlations with the PAS scores were not observed in healthy
      subjects. This study provides further evidences of the role of the hippocampus
      and nucleus accumbens in trait physical anhedonia and possible associations
      between emotional memory deficit and trait physical anhedonia in patients with
      schizophrenia.

PMID- 22867953
TI  - Left amygdalar activation in deficit syndrome compared with non-deficit subjects
      with schizophrenia during the control task in a facial emotion recognition
      paradigm.

PMID- 22867954
TI  - Haematobium eggs detection in human bladder cancer and sporocysts in snail
      vectors: Seven cases report and a review of the Burkina Faso literature.
AB  - Schistosoma haematobium plays a central role in the development of bladder cancer
      in Burkina Faso. The objective of this study was to determine the presence of S.
      haematobium in the bladder cancer and in vector snails. For the first time,
      formalin-fixed tissues embedded in paraffin were analyzed by immunohistochemistry
      and PCR. Molecular detection has resulted in 7/7 positive bladder cancer.
      Finally, as the snail vectors were positive. We suggest the use of molecular
      methods in the snail vectors for the detection of cysts and in cancerous tissues
      in larger studies.

PMID- 22867955
TI  - [Facial allografts and oral rehabilitation].
AB  - The main objective of facial allografts is functional. On this account, oral
      rehabilitation is pivotal. Two types of cases are possible. Firstly, the
      indication of facial allograft concerns only the soft tissues. If so, dental care
      is similar to the one of patients with an organ transplant. Dental implants are a
      priori contraindicated. A possible indication has to be discussed with the
      multidisciplinary team. Secondly, the indication is the one of a mandibular
      and/or maxillary reconstruction. The objective will be a total reconstruction. It
      could be performed immediately with the allotransplantation of a toothed mandible
      or maxillar, if the local status permits it. To date, among patients who have
      benefited from a toothed allotransplant, no tooth has been lost. The first cases
      have been operated in 2009. If donor teeth cannot be conserved with the
      allotransplant, the oral rehabilitation will have to be done ideally with
      adjunctive prostheses. It is rarely possible, for example because of the lack of
      crests. In case of impossibility, an implant-based rehabilitation can be
      discussed. One case has been performed with basal implants (cortically anchored
      disk-design implants) with a five-year follow-up without loosing any loss of
      implant or infection.

PMID- 22867956
TI  - Traditional risk factors for Helicobacter pylori infection not found among
      patients undergoing diagnostic upper endoscopy-Republic of Georgia, 2007-2008.
AB  - OBJECTIVES: Helicobacter pylori causes gastritis, duodenal ulcers, and gastric
      cancer. Although household crowding, low socioeconomic status (SES), and poor
      sanitation are associated with infection elsewhere, risk factors of infection in
      the Republic of Georgia (ROG), a country with a high prevalence rate (>70%),
      remain unknown. In this study we explored potential risk factors of infection
      among symptomatic patients in ROG. METHODS: During 2007-2008, we prospectively
      recruited 390 subjects with gastrointestinal symptoms referred to five tertiary
      care centers for diagnostic upper endoscopy. We administered a questionnaire on
      potential risk factors and tested patients using three diagnostic tests: gastric
      biopsies underwent histological evaluation and rapid urease test (CLO test), and
      an ELISA was used to detect IgG against H. pylori in serum. We defined a case as
      having two or more positive results from the three available tests. Univariate
      and multivariate logistic regression analyses were performed. RESULTS: Overall,
      217 (56%) patients met the study case definition. Subjects diagnosed with cancer
      had the highest rate of H. pylori infection (62%), followed by those with
      gastritis (55%), and ulcer (54%). Age >30 years (adjusted odds ratio (aOR 2.6,
      95% confidence interval (CI) 1.6-4.3) and residing in the capital city (aOR 0.6,
      95% CI 0.4-0.9) were significantly associated with infection. CONCLUSIONS: In
      this large cohort with gastrointestinal symptoms, only age >30 years and living
      in the capital were significant factors associated with infection. Lower SES,
      less education, and crowding did not confer an increased risk, in contrast to the
      findings of previous studies. Population-based studies are needed to identify
      potential routes and risk factors of H. pylori infection in ROG.

PMID- 22867957
TI  - Single trial time-frequency domain analysis of error processing in post-traumatic
      stress disorder.
AB  - Error processing studies in psychology and psychiatry are relatively common.
      Event-related potentials (ERPs) are often used as measures of error processing,
      two such response-locked ERPs being the error-related negativity (ERN) and the
      error-related positivity (Pe). The ERN and Pe occur following committed error in
      reaction time tasks as low frequency (4-8 Hz) electroencephalographic (EEG)
      oscillations registered at the midline fronto-central sites. We created an
      alternative method for analyzing error processing using time-frequency analysis
      in the form of a wavelet transform. A study was conducted in which subjects with
      PTSD and healthy control completed a forced-choice task. Single trial EEG data
      from errors in the task were processed using a continuous wavelet transform.
      Coefficients from the transform that corresponded to the theta range were
      averaged to isolate a theta waveform in the time-frequency domain. Measures
      called the time-frequency ERN and Pe were obtained from these waveforms for five
      different channels and then averaged to obtain a single time-frequency ERN and Pe
      for each error trial. A comparison of the amplitude and latency for the time
      frequency ERN and Pe between the PTSD and control group was performed. A
      significant group effect was found on the amplitude of both measures. These
      results indicate that the developed single trial time-frequency error analysis
      method is suitable for examining error processing in PTSD and possibly other
      psychiatric disorders.

PMID- 22867958
TI  - Genetic analysis of the LAMP-2 gene promoter in patients with sporadic
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease in the people of
      over 65. Majority of PD is sporadic, which is caused by interaction of genetic
      and environmental factors. To date, genetic causes and underlying molecular
      mechanisms for sporadic PD remain largely unknown. Autophagy is a conserved
      cellular degradative process, consisting of macroautophagy, microautophagy and
      chaperone-mediated autophagy (CMA). Macroautophagy (hereafter referred to as
      autophagy) and CMA are involved in the degradation of alpha-synuclein, a critical
      protein in the PD pathogenesis. Previous studies with brain tissues and
      leukocytes have shown that the expression levels of lysosome-associated membrane
      2 (LAMP-2) gene are significantly decreased in PD patients. In this study, we
      genetically and functionally analyze the promoter region of LAMP-2 gene in
      sporadic PD patients. Two novel sequence variants and two single nucleotide
      polymorphisms (SNPs) were identified. The heterozygous variant, g.4127A>C, which
      was only found in one female PD patient, significantly reduced the
      transcriptional activities of LAMP-2 gene promoter. The hemizygous variant,
      g.5038G>A, which was only found in one male control, enhanced the transcriptional
      activities of LAMP-2 gene promoter. No significant difference in frequencies of
      the SNPs, rs42900 (g.4569A>C) and rs28603270 (g.4760T>G), was observed between PD
      patients and controls. Collectively, the sequence variants within the LAMP-2 gene
      promoter may be linked to the PD onset by changing LAMP-2 protein levels and
      impairing autophagy and CMA activities.

PMID- 22867959
TI  - [Psoriatic arthritis mutilans].

PMID- 22867960
TI  - Ethics in radiology: wait lists queue jumping.
AB  - Education in ethics is a requirement for all Royal College residency training
      programs as laid out in the General Standards of Accreditation for residency
      programs in Canada. The ethical challenges that face radiologists in clinical
      practice are often different from those that face other physicians, because the
      nature of the physician-patient interaction is unlike that of many other
      specialties. Ethics education for radiologists and radiology residents will
      benefit from the development of teaching materials and resources that focus on
      the issues that are specific to the specialty. This article is intended to serve
      as an educational resource for radiology training programs to facilitate teaching
      ethics to residents and also as a continuing medical education resource for
      practicing radiologists. In an environment of limited health care resources,
      radiologists are frequently asked to expedite imaging studies for patients and,
      in some respects, act as gatekeepers for specialty care. The issues of wait
      lists, queue jumping, and balancing the needs of individuals and society are
      explored from the perspective of a radiologist. 

PMID- 22867961
TI  - Retrospective review of efficacy of radiofrequency ablation for treatment of
      colorectal cancer liver metastases from a Canadian perspective.
AB  - PURPOSE: A retrospective single-center review of ultrasound-guided radiofrequency
      ablation (RFA) treatment of colorectal cancer liver metastases was performed.
      This study reviews the primary and secondary technical effectiveness, overall
      survival of patients, recurrence-free survival, tumour-free survival, rates of
      local recurrence, and postprocedural RFA complications. Technical effectiveness
      and rates of complication with respect to tumour location and size were
      evaluated. Our results were compared with similar studies from Europe and North
      America. METHODS: A total of 63 patients (109 tumours) treated with RFA between
      February 2004 and December 2009 were reviewed. Average and median follow-up time
      was 19.4 and 16.5 months, respectively (range, 1-54 months). Data from patient
      charts, pathology, and Picture Archiving and Communication System was integrated
      into an Excel database. Statistical Analysis Software was used for statistical
      analysis. RESULTS: Primary and secondary technical effectiveness of percutaneous
      and intraoperative RFA were 90.8% and 92.7%, respectively. Average (SE) tumour
      free survival was 14.4 +/- 1.4 months (range, 1-43 months), and average (SE)
      recurrence-free survival was 33.5 +/- 2.3 months (range, 2-50 months). Local
      recurrence was seen in 31.2% of treated tumours (range, 2-50 months) (34/109).
      Overall survival was 89.4% at 1 year, 70.0% at 2 years, and 38.1% at 3 years,
      with an average (SE) overall survival of 37.0 +/- 2.8 months. There were 14
      postprocedural complications. There was no statistically significant difference
      in technical effectiveness for small tumours (1-2 cm) vs intermediate ones (3-5
      cm). There was no difference in technical effectiveness for peripheral vs
      parenchymal tumours. CONCLUSIONS: This study demonstrated good-quality outcomes
      for RFA treatment of colorectal cancer liver metastases from a Canadian
      perspective and compared favorably with published studies.

PMID- 22867962
TI  - Catheter fracture and embolization associated with arm implantation of the cook
      vital port.
AB  - PURPOSE: To determine the frequency of arm port catheter fracture and
      embolization related to the Cook Vital Port Mini Titanium. MATERIALS AND METHODS:
      A retrospective audit of our Cerner Radiology Information System was performed
      between June 1, 2006, and June 30, 2011, to determine the number of Cook arm
      venous ports implanted and the frequency of foreign body retrievals related to
      catheter fracture for these arm ports. RESULTS: A total of 691 arm implantations
      of the Cook Vital Port during the 5-year time frame were analysed. Eleven of
      these patients (1.6%) required intravenous foreign body retrieval in the
      interventional radiology suite related to catheter fracture and embolization.
      Three of these fractured catheters were retrieved from the peripheral venous
      system upstream of the pulmonary circulation, whereas 8 embolized to the
      pulmonary arteries. All were successfully extracted with an intravenous snare by
      interventional radiology. CONCLUSION: We discovered a 1.6% frequency of catheter
      fracture and embolization associated with arm implantation of the Cook Vital
      Port. All the catheters fractured at the vein entry site and did not detach from
      the port housing. The cause for catheter fracture and embolization is uncertain.
      Pulmonary embolization of the fractured catheters puts the patients at risk for
      possible further complications. No patients had ancillary complications related
      to catheter embolization or to catheter extraction procedures. Further
      investigation is required in an attempt to determine the circumstances that may
      result in catheter fracture and embolization related to this venous access
      device.

PMID- 22867963
TI  - Ultrasound-guided fine-needle aspiration biopsy of the thyroid: methods to
      decrease the rate of unsatisfactory biopsies in the absence of an on-site
      pathologist.
AB  - PURPOSE: The rate of unsatisfactory samples from ultrasound-guided fine-needle
      aspirations of thyroid nodules varies widely in the literature. We aimed to
      evaluate our thyroid ultrasound-guided fine-needle aspiration biopsy technique in
      the absence of on-site microscopic examination by a pathologist; determine
      factors that affect the adequacy rate, such as the number of needle passes and
      needle size; compare our results with the literature; and establish an optimal
      technique. MATERIALS AND METHODS: We performed a retrospective review of
      cytopathology reports from 252 consecutive thyroid ultrasound-guided fine-needle
      aspiration biopsies performed by a radiologist between 2005 and 2010 in our
      hospital's radiology department. Sample adequacy, the number of needle passes,
      and needle size were determined. There was an on-site cytologist who prepared
      slides immediately after fine-needle aspiration but no on-site microscopic
      assessment of sample adequacy to guide the number of needle passes that should be
      performed. Cytopathology biopsy reports were classified as either unsatisfactory
      or satisfactory samples for diagnosis; the latter consisted of benign, malignant,
      and undetermined diagnoses. RESULTS: Seventy-seven biopsies were performed with 1
      needle pass, 124 with 2 needle passes, and 51 with 3 needle passes. The rates of
      unsatisfactory biopsies were 33.8%, 23.4% (odds ratio [OR] 0.599 [95% confidence
      interval {CI}, 0.319-1.123]; P = .110), and 13.7% (OR 0.312 [95% CI, 0.124
      0.788]; P = .014), respectively. CONCLUSION: In a hospital in which there is no
      on-site pathologist, a 3-pass method increases the specimen satisfactory rate by
      20% compared with 1 pass, achieves similar rates to the literature, and provides
      a basis for further improvement of our practice.

PMID- 22867964
TI  - Editorial overview.

PMID- 22867965
TI  - The effects of increased freshwater salinity in the biodisponibility of metals
      (Cr, Pb) and effects on antioxidant systems of Oreochromis niloticus.
AB  - Anthropogenic activities can increase the salinity of freshwaters and this may
      cause stress for fish and affect metal bioavailability. Oxidative stress
      biomarkers are of great interest due to their responses to environmental
      stressors which provide valuable data for biological monitoring of aquatic
      pollution. Thus, the individual and combined effects of salinity and metals (Cr,
      Pb) were investigated in the liver of freshwater fish Oreochromis niloticus in
      the present study. Fish were exposed to salinity (2 and 8 ppt) alone and
      salinity+metal (1 MUg/mL Pb and Cr) combination exposures for 0, 1, 7 and 14 days
      and subsequently antioxidant enzymes (superoxide dismutase, SOD; glutathione
      peroxidase, GPX; glutathione reductase, GR and glutathione S-transferase, GST)
      activities and glutathione (GSH) levels in the liver were measured. Data showed
      that all the parameters varied in relation to metal species, exposure durations
      and salinity levels. Profound alterations on the measured parameters were
      detected at the lower salinity compared to the higher one. Salinity increase
      effectively stimulated the antioxidant parameters. The effects of salinity and
      metals on the measured parameters increased as the exposure duration prolonged.
      SOD was the most affected antioxidant parameter from both salinity and metals.
      Because metal and salinity stresses affect fish antioxidant system, this work
      suggests that the chemistry of freshwaters should be taken into account in
      natural monitoring for metal contamination in the field.

PMID- 22867967
TI  - Flecainide and antiarrhythmic effects in a mouse model of catecholaminergic
      polymorphic ventricular tachycardia.
AB  - Recent studies have shown that flecainide may be an effective therapy to prevent
      life-threatening arrhythmias in patients with catecholaminergic polymorphic
      ventricular tachycardia. Several hypotheses have been advanced to explain the
      antiarrhythmic mechanism of flecainide, including Na(+) channel blockade and a
      direct inhibitory action on the ryanodine receptor. In this article, we review
      the current literature on the topic and summarize the elements of the existing
      debate.

PMID- 22867966
TI  - A rat model system to study complex disease risks, fitness, aging, and longevity.
AB  - The association between low exercise capacity and all-cause morbidity and
      mortality is statistically strong yet mechanistically unresolved. By connecting
      clinical observation with a theoretical base, we developed a working hypothesis
      that variation in capacity for oxygen metabolism is the central mechanistic
      determinant between disease and health (aerobic hypothesis). As an unbiased test,
      we show that two-way artificial selective breeding of rats for low and high
      intrinsic endurance exercise capacity also produces rats that differ for numerous
      disease risks, including the metabolic syndrome, cardiovascular complications,
      premature aging, and reduced longevity. This contrasting animal model system may
      prove to be translationally superior relative to more widely used simplistic
      models for understanding geriatric biology and medicine.

PMID- 22867968
TI  - New reservoirs of HLA alleles: pools of rare variants enhance immune defense.
AB  - Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in
      humans) encode critical amino acids that bind foreign peptides. Recognition of
      the peptide-MHC complexes by T cells initiates the adaptive immune response. The
      particular structure of these exons facilitates gene conversion(GC) events,
      leading to the generation of new alleles. Estimates for allele creation and loss
      indicate that more than 10000 such alleles are circulating at low frequencies in
      human populations. Empirical sampling has affirmed this expectation. This
      suggests that the MHC loci have a system for moving valuable and often complex
      variants into adaptive service. Here, we argue that HLA loci carry many new
      mutant alleles prepared to assume epidemiologically meaningful roles when called
      on by selection provoked by exposure to new and evolving pathogens. Because new
      mutant alleles appear in a population at the lowest possible frequency (i.e., a
      single copy), they have typically been thought of as having little consequence.
      However, this large population of rare yet potentially valuable new alleles may
      contribute to pathogen defense.

PMID- 22867969
TI  - SIRT1 promotes proliferation and inhibits apoptosis of human malignant glioma
      cell lines.
AB  - In mammalian cells, SIRT1 decreases PTEN acetylation and inactivates the AKT
      pathway in a SIRT1 deacetylase-dependent manner. However, the function of SIRT1
      in glioma was unknown. SIRT1 reexpression or knockdown was induced in human
      glioma cell lines. The cell synchronization, BrdU labeling and mitotic index were
      detected. Subsequently, cell cycle, cell viability, apoptosis, cell growth and
      proliferation were analyzed. Our work identified that SIRT1-knockdown
      significantly delayed mitotic entry of glioma cells, inhibited its growth and
      proliferation, and promoted its apoptosis. The apoptosis was related to
      PTEN/PI3K/AKT signaling pathway. The results showed that SIRT1 might be a
      promoter factor on tumorigenesis of glioma through PTEN/PI3K/AKT signaling
      pathway.

PMID- 22867970
TI  - The gamma-secretase inhibitor DAPT increases the levels of gangliosides at
      neuritic terminals of differentiating PC12 cells.
AB  - Mutations in presenilins are the major cause of early onset familial Alzheimer
      disease. It has recently been argued that clinical presenilin mutations work as
      loss-of-function but not toxic gain-of-function. To investigate whether
      presenilins are involved in the regulation of the distribution of neuronal
      membrane lipids, we treated neuronally differentiated PC12 cells with DAPT, an
      inhibitor of presenilin-dependent gamma-secretase, and performed lipid analyses
      of neuritic terminals, which is an initial site of Abeta deposition in brains,
      using liquid chromatography/electrospray ionization tandem mass spectrometry
      (LC/ESI-MS/MS) in combination with multiple reaction monitoring (MRM). With DAPT
      treatment, levels of sphingomyelin, phosphatidylcholine, and cholesterol remained
      unchanged. However, DAPT treatment increased the ganglioside levels in PC12
      neuritic terminals. Together with a previous finding that accumulation of
      gangliosides at neuritic terminals facilitates Abeta assembly and deposition, the
      present data suggest that the loss-of-function of presenilins, i.e., a decrease
      in gamma-secretase activity, has an impact on neuronal membrane architecture in a
      way that eventually exacerbates Alzheimer pathology.

PMID- 22867971
TI  - Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse
      model for dengue virus infection informs dosing regimen for a proof of concept
      clinical trial.
AB  - Celgosivir (6-O-butanoyl castanospermine), a pro-drug of the naturally occurring
      castanospermine, is an inhibitor of alpha-glucosidase I and II that is found to
      be a potent inhibitor of several enveloped viruses including all four serotypes
      of dengue virus. We showed previously that the compound fully protected AG129
      mice from lethal infection with a mouse adapted dengue virus at a dose of 50mg/kg
      twice daily (BID) for 5days and was effective even after 48h delayed treatment.
      Here we show that the protection by celgosivir is dose- and schedule-dependent
      and that a twice-a-day regimen of 50, 25 or 10mg/kg is more protective than a
      single daily dose of 100mg/kg. Treatment with 50mg/kg BID castanospermine had
      comparable efficacy as 25mg/kg BID celgosivir, suggesting that celgosivir is
      approximately twice as potent as castanospermine with respect to in vivo
      antiviral efficacy. Pharmacokinetics (PK) studies of celgosivir in mice showed
      that it rapidly metabolized to castanospermine. Simulation of the PK data with
      the survival data for the various doses of celgosivir tested suggests that the
      steady-state minimum concentration is a critical parameter to note in choosing
      dose and schedule. These results influenced the selection of the dose regimen for
      a proof-of-concept clinical trial of celgosivir as a treatment against dengue
      fever.

PMID- 22867972
TI  - Nondermatomal somatosensory deficits in chronic pain patients: are they really
      hysterical?
AB  - Patients with chronic pain disorders frequently show nondermatomal somatosensory
      deficits (NDSDs) that are considered to be functional. Typically, NDSDs show
      quadratomal or hemibody distribution ipsilateral to the areas of chronic pain.
      According to the Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition and the International Classification of Diseases, 10th revision, such
      functional somatosensory deficits are classified in the chapter "conversion
      disorder." Many publications also used the term "hysterical sensory loss."
      However, doubts are increasing about this one-sided psychiatric view. We aimed to
      better characterize the biopsychosocial factors associated with NDSDs. Therefore,
      we compared 2 groups of inpatients with chronic pain disorder, of whom 90
      suffered from NDSDs and 90 did not. The patients with NDSDs all showed widespread
      somatosensory deficits with hemibody distribution. On logistic regression
      analysis, history of a prior physical trauma was positively predictive for
      patients with NDSDs. Personality disorder and adverse childhood experiences were
      positively predictive for the control group with chronic pain disorders without
      NDSDs. The frequencies of comorbid depression and anxiety disorder did not differ
      statistically between groups. In conclusion, pain patients with NDSDs are,
      psychopathologically, by no means more noticeable personalities than patients
      with chronic pain disorder without NDSDs. Similar to complex regional pain
      syndromes, we assume a multifactorial etiology of NDSDs, including stress. Based
      on our observations, terms like "hysteric" should not be applied any longer to
      patients with NDSDs who suffer from chronic pain.

PMID- 22867973
TI  - Negative effects of ultrafine particle exposure during forced exercise on the
      expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats.
AB  - Exercise improves cognitive function, and Brain-Derived Neurotrophic Factor
      (BDNF) plays a key role in this process. We recently reported that particulate
      matter (PM) exposure negatively contributed to the exercise-induced increase in
      human serum BDNF concentration. Furthermore, PM exposure is associated with
      neuroinflammation and cognitive decline. The aim of this study was to investigate
      the effect of exposure to ultrafine particles (UFP) during a single bout of
      forced exercise on the expression of inflammatory (IL1alpha, IL1beta, TNF, IL6,
      NOS2, NOS3) and oxidative stress (NFE2L2)-related genes, as well as BDNF in the
      brain of rats. Four groups (n=6/group) of Wistar rats were exposed for 90 min to
      one of the following exposure regimes: UFP+exercise, UFP+rest, ambient
      air+exercise, ambient air+rest (control). Hippocampus, olfactory bulb and
      prefrontal cortex were collected 24h after exposure. Gene expression changes were
      analyzed with real-time PCR. In the condition ambient air+exercise, hippocampal
      expression of BDNF and NFE2L2 was up-regulated, while the expression of IL1alpha
      and NOS3 in the prefrontal cortex and IL1alpha in the olfactory bulb was down
      regulated compared to the control. In contrast, gene expression in the condition
      UFP+exercise did not differ from the control. In the condition UFP+rest,
      hippocampal expression of NFE2L2 was down-regulated and there was a trend toward
      down-regulation of BDNF expression compared to the control. This study shows a
      negative effect of UFP exposure on the exercise-induced up-regulation of BDNF
      gene expression in the hippocampus of rats.

PMID- 22867974
TI  - Valproate promotes survival of retinal ganglion cells in a rat model of optic
      nerve crush.
AB  - Valproate (VPA) is an anticonvulsant and mood-stabilizing drug. It is a broad
      spectrum histone deacetylase inhibitor with neuroprotective effects. We
      investigated whether VPA reduces retinal neuronal death induced by optic nerve
      crush (ONC). To evaluate further VPA-mediated neuroprotection on retinal ganglion
      cells (RGCs), another histone deacetylase (HDAC) inhibitor, sodium butyrate (SB)
      was compared with VPA. Adult male Wistar rats were subjected to ONC injury. VPA
      and SB were administered subcutaneously 1 day prior to ONC until sacrifice 14
      days later. RGC density was counted using hematoxylin and eosin (H&E) staining of
      the retinal section and retrograde labeling with FluoroGold. Retinal function was
      evaluated by electroretinography (ERG) after ONC. Immunofluorescence of activated
      caspase-3 in ganglion cell layer (GCL) and the detection of bcl-2 mRNA expression
      in the retina were used to evaluate apoptosis of retinal cells. In addition,
      brain-derived neurotrophic factor (BDNF) in retinas was measured using an enzyme
      linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR).
      Western blot was used to analyze histone H3 acetylation, the protein kinase B
      (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation levels, and
      tropomyosin-related kinase B (TrkB) levels. The transcriptional activation of the
      BDNF gene was analyzed by measuring the levels of acetylation or methylation of
      histone H3 using chromatin immunoprecipitation assay. The RGC density in the VPA
      and SB treated-groups were significantly higher as compared with those of the
      corresponding vehicle group following ONC. VPA and SB suppressed reductions in a-
      and b-wave amplitudes of the ERG and attenuated the activation of caspase-3 in
      the RGCs, which was accompanied by upregulation in Akt and Erk phosphorylation in
      the retina. Furthermore, VPA upregulated levels of bcl-2, BDNF, TrkB in the
      retina post-injury. VPA and SB treatment resulted in the hyperacetylation of
      histone H3K14, attenuated histone H3K9 hypermethylation in the BDNF promoter, and
      promoted transcriptional activity. These results demonstrate that VPA appears to
      protect RGCs from ONC by inhibiting neuronal apoptosis possibly via the
      activation of BDNF-TrkB signaling and HDAC inhibition.

PMID- 22867975
TI  - Blockade of intra-articular TNF in peripheral spondyloarthritis: its relevance to
      clinical scores, quantitative imaging and synovial fluid and synovial tissue
      biomarkers.
AB  - OBJECTIVES: This open-label study is based on a translational approach with the
      aim of detecting changes in the clinical condition as well as in imaging and
      synovial biological markers in both synovial fluid (SF) and synovial tissue (ST)
      in peripheral spondyloarthritis (SpA) patients following intra-articular (IA)
      blockade of TNF-alpha by serial etanercept injections. METHODS: Twenty-seven SpA
      patients with resistant knee synovitis underwent four biweekly IA injections of
      etanercept (E) (12.5 mg). The primary outcome of Thompson's Knee Index (THOMP),
      and secondary outcomes of Knee Joint Articular Index (KJAI), C-reactive protein
      (CRP), HAQ-Disability Index (HAQ-DI), maximal synovial thickness (MST) according
      to ultrasonography (US) and contrast-enhanced magnetic resonance (C+MR) imaging,
      ST-CD45+ mononuclear cells (MNC) and ST-CD31+ vessels, IL-1beta, IL-1Ra and IL-6
      levels in SF were assessed at baseline and at the end of the study. RESULTS: At
      the study end, clinical and imaging outcomes as well as ST and SF biological
      markers were significantly reduced compared to baseline. There were significant
      correlations between clinical, imaging and biological markers (CRP with either
      THOMP, or KJAI, or HAQ-DI or SF-IL-1Ra; US-MST with KJAI, ST-CD45+ with either
      THOMP, or KJAI, or ST-CD31+, or SF-IL-1beta; SF-IL-6 with either THOMP, or KJAI,
      or SF-IL-1beta, or IL-1Ra). CONCLUSIONS: The proof of concept study revealed
      early improvement either in local and systemic clinical scores, in synovial
      thickness measures by C+MR and US, or expression of synovial biological markers.
      CD45+, CD31+ in ST and IL-6 and IL-1beta in SF may be considered potential
      biomarkers of the peripheral SpA response to IA TNF-alpha blocking.

PMID- 22867976
TI  - Gout and osteoarthritis: a pathogenetic link?

PMID- 22867977
TI  - Asymmetric elongation of foveal tissue after macular hole surgery and its impact
      on metamorphopsia.
AB  - PURPOSE: To evaluate the elongation profile of foveal tissue after macular hole
      (MH) surgery and to investigate its impact on visual function. DESIGN:
      Prospective, interventional case series. PARTICIPANTS: Thirty-one eyes from 31
      patients who underwent surgery for an MH less than 400 MUm in diameter. METHODS:
      The distance between the parafoveal edge of the outer plexiform layer (OPL) was
      defined as the inter-OPL distance and measured on the basis of optical coherence
      tomography images at the first postoperative visit and the 2- and 6-month
      postoperative visits. Further elongation of the foveal tissue in certain
      directions was defined as asymmetric elongation. The association of the mean
      degree of asymmetric elongation with visual acuity and metamorphopsia score (M
      score) outcome was evaluated. MAIN OUTCOME MEASURES: Inter-OPL distance and M
      score. RESULTS: Macular hole sealing was noted in all eyes after surgery. The
      horizontal inter-OPL distances measured at the defined time points were 361.6+/
      99.6 MUm, 558.8+/-93.3 MUm, and 575.4+/-94.8 MUm, respectively. The vertical
      inter-OPL distances were 324.2+/-93.8 MUm, 481.2+/-104.6 MUm, and 494.6+/-85.0
      MUm, respectively. Both the horizontal and vertical inter-OPL distances were
      increased during the follow-up period (P<0.001). Horizontal inter-OPL distances
      were significantly longer than vertical distances at 1, 2, and 6 months (P<0.001,
      P<0.001, and P<0.001, respectively). Further nasal and superior elongation was
      noted on the horizontal and vertical planes in 90.3% and 61.3% of eyes,
      respectively. The mean degree of asymmetric spreading was significantly
      associated with an M-score at 6 months postoperatively (P = 0.044) and a
      difference in M-score between preoperative and 6-month postoperative examinations
      (P = 0.027). CONCLUSIONS: Elongation of the foveal tissue was noted after MH
      surgery. This elongation was usually asymmetric, and the degree of asymmetry was
      associated with postoperative metamorphopsia.

PMID- 22867978
TI  - Use of containers with sterilizing filter in autologous serum eyedrops.
AB  - OBJECTIVE: To assess the effect of the use of containers with an adapted
      sterilizing filter on the contamination of autologous serum eyedrops. DESIGN:
      Prospective, consecutive, comparative, and randomized study. PARTICIPANTS: Thirty
      patients with Sjogren syndrome. METHODS: One hundred seventy-six autologous serum
      containers used in home therapy were studied; 48 of them included an adapted
      filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were
      conventional containers. Containers equipped with a filter were tested at 7, 14,
      21, and 28 days of use, whereas conventional containers were studied after 7 days
      of use. In addition, testing for contamination was carried out in 14 conventional
      containers used during in-patient therapy every week for 4 weeks. In all cases,
      the preparation of the autologous serum was similar. Blood agar and chocolate
      agar were used as regular culture media for the microbiologic studies, whereas
      Sabouraud agar with chloramphenicol was the medium for fungal studies. MAIN
      OUTCOMES MEASURES: Microbiologic contamination of containers with autologous
      serum eyedrops. RESULTS: Only one of the containers with an adapted sterilizing
      filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month
      of treatment, whereas the contamination rate among conventional containers
      reached 28.9% after 7 days of treatment. The most frequent germs found in the
      samples were coagulase-negative Staphylococcus (48.6%). With regard the
      containers used in the in-patient setting, 2 (14.3%) became contaminated after 2
      weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became
      contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated
      after 1 month of treatment. CONCLUSIONS: Using containers with an adapted filter
      significantly reduces the contamination rates in autologous serum eyedrops, thus
      extending the use of such container by the patients for up to 4 weeks with
      virtually no contamination risks.

PMID- 22867979
TI  - Different risk factors between interstitial lung disease and airway disease in
      rheumatoid arthritis.
AB  - OBJECTIVE: To identify clinical and genetic risk factors for interstitial lung
      disease (ILD) or airway disease (AD) in patients with rheumatoid arthritis (RA)
      and to evaluate differences between the associations of these factors with ILD
      and AD. METHODS: We reviewed high-resolution computed tomography (HRCT) images
      and clinical data of 356 RA patients obtained at their first visit. The diagnosis
      of ILD and AD was based on abnormal HRCT findings. Multinomial logistic
      regression analysis and likelihood ratio tests were performed. RESULTS: High
      titers of rheumatoid factor are similarly associated with increased risks of ILD
      (relative risk ratio, 3.1; p = 0.02) and AD (relative risk ratio, 3.0; p = 0.02).
      High levels of anti-cyclic citrullinated peptide antibodies were associated
      strongly with AD (relative risk ratio, 3.8; p = 0.005) and less strongly with ILD
      (relative risk ratio, 2.7; p = 0.07). Age was the potent risk factor for ILD
      (relative risk ratio, 4.6; p = 0.003), while that for AD was advanced stage
      (relative risk ratio, 11.5; p < 0.0005). The carriage of HLA-DRB1*1502 had
      opposite influences on the two conditions: relative risk ratio = 4.02 for ILD (p
      = 0.013) and relative risk ratio = 0.15 for AD (p = 0.08). This difference was
      statistically significant (p = 0.0005). Associations of sex and smoking history
      with ILD disappeared in the multinomial logistic regression analysis.
      CONCLUSIONS: The differential associations of ILD and AD with various clinical
      and genetic factors suggest that ILD and AD have distinct etiologies in RA.

PMID- 22867980
TI  - Thrombus through a patent foramen ovale: a direct cause of cardioembolic stroke
      and pulmonary embolism.

PMID- 22867981
TI  - An integer programming approach for optimal drug dose computation.
AB  - In this paper, we study the problem of determining the optimal drug
      administration strategy when only a finite number of different dosages are
      available, a lower bound is posed on the time intervals between two consecutive
      doses, and drug concentrations should not exceed the toxic concentration levels.
      The presence of only binary variables leads to the adoption of an integer
      programming (IP) scheme for the formulation and solution of the drug dose optimal
      control problem. The proposed method is extended to account for the stochastic
      formulation of the optimal control problem, so that it can be used in practical
      applications where large populations of patients are to be treated. A Finite
      Impulse Response (FIR) model derived from experimental pharmacokinetic data is
      employed to correlate the administered drug dose with the concentration-time
      profiles of the drug in the compartments (organs) of the body.

PMID- 22867982
TI  - Cosmetic procedures screening (COPS).

PMID- 22867983
TI  - Double nerve transfer for elbow flexion in obstetric brachial plexus injury: a
      case report.
AB  - We report a case of a 10-month-old boy with a left extended upper type (C5-C7)
      obstetric brachial plexus injury that was treated with double nerve transfer
      (partial ulnar and partial median nerve transfer) to restore elbow flexion and
      spinal accessory nerve transfer to the suprascapular nerve to restore shoulder
      abduction. At 60 months' follow-up, shoulder abduction was 0-150 degrees  (M4)
      and elbow flexion was 0-140 degrees  (M5). Elbow, wrist and finger extension
      improved to M5. However, shoulder external rotation was only 0-30 degrees  (from
      full internal rotation). No weakness on finger and wrist flexion was observed.
      Double nerve transfers to restore elbow flexion can be safely done in obstetric
      brachial plexus injuries with good results. Secondary surgeries may be needed to
      improve external rotation.

PMID- 22867984
TI  - Reconstruction of massive localised lymphoedema of the scrotum with a novel
      fasciocutaneous flap: A rare case presentation and a review of the literature.
AB  - Massive localised lymphoedema (MLL) is a benign lymphoproliferative soft-tissue
      overgrowth in the morbidly obese patient. The diagnosis may be challenging, and
      is a form of secondary lymphoedema, often described as idiopathic scrotal
      elephantiasis. The lesion presents as a large mass in the morbidly obese, and
      patients seek treatment late in the disease course due to limitation of daily
      living or excoriation and wound breakdown. Resection, followed by reconstruction,
      is indicated in these cases. We present a unique case of a morbidly obese 52-year
      old male with massive enlargement of the scrotum present for several years
      duration, despite massive weight loss (88.85 kg) from gastric bypass surgery and
      no other identifiable cause of lymphoedema. Scrotal lymphoedematous tissue was
      resected and scrotal reconstruction with a novel posterior fasciocutaneous flap
      from the scrotum was performed in addition to penile reconstruction with a skin
      graft and local fasciocutaneous flaps as well as a panniculectomy.
      Histologically, the tissue was characterised by marked oedema with dermal
      fibrosis and patchy mild perivascular chronic inflammation. Postoperative follow
      up revealed wound integrity and patient satisfaction with the outcome. MLL is an
      important disease process with distinct clinical and histopathologic
      characteristics that often requires complex reconstruction. Although there are
      several opposing classification schema, we propose the incorporation of
      idiopathic scrotal elephantiasis into the diagnostic category of MLL.

PMID- 22867985
TI  - Clinical characteristics and outcomes of patients with cardiac defects and
      congenital diaphragmatic hernia.
AB  - OBJECTIVE: To evaluate the impact of associated heart defects on outcomes to
      discharge, and identify factors affecting survival of all infants born with
      congenital diaphragmatic hernia (CDH) in last decade using Congenital
      Diaphragmatic Hernia Study Group data. STUDY DESIGN: This was a retrospective
      review of all infants with CDH enrolled in Congenital Diaphragmatic Hernia Study
      Group database from January 2000 to December 2010. The study cohort was divided
      into 3 groups (GRP): GRP 1, CDH with major heart defects; GRP 2, CDH with minor
      heart defects; and GRP 3, CDH with no reported heart defects. RESULTS: The 4268
      enrolled infants included 345 (8%) in GRP 1, 412 (10%) in GRP 2, and 3511 (82%)
      in GRP 3. Survival was significantly lower in GRP 1 compared with GRP 2 and GRP 3
      (36% vs 73%). In GRP 1, the most common defects were left heart obstructive
      lesions (34%). Survival was lowest in infants with transposition of great
      arteries (0%) and single ventricle physiology (16%). There was no change in
      survival rate for any group between 2000-2005 and 2006-2010. In GRP 1, factors
      that predicted lower survival were birth weight <2.5 kg, associated noncardiac
      anomalies, single ventricle physiology, no sildenafil therapy, no CDH repair, and
      no cardiac repair. CONCLUSION: Survival is significantly lower in patients with
      CDH and major heart defects compared with patients with minor or no heart
      defects. Outcomes of newborns with CDH and major heart defects have not improved
      over the last decade.

PMID- 22867986
TI  - Preventing hidden hunger in children using micronutrient supplementation.

PMID- 22867987
TI  - BJ-PI2, a non-hemorrhagic metalloproteinase from Bothrops jararaca snake venom.
AB  - BACKGROUND: Envenoming by Bothrops jararaca can result in local pain, edema,
      hemorrhage and necrosis, partially mediated by snake venom metalloproteinases
      (SVMPs). Here, we describe the characterization of BJ-PI2, a P-I class SVMP from
      B. jararaca venom, and its local tissue actions. METHODS: BJ-PI2 was purified by
      a combination of gel filtration, anion-exchange chromatography and reverse phase
      HPLC, and identified by mass spectrometry. Clotting and fibrin(ogen)olytic
      activities were assayed using conventional methods. Hemorrhagic activity and
      changes in vascular permeability were examined in rat dorsal skin. Myonecrosis
      and inflammatory activity were examined in mouse gastrocnemius muscle. RESULTS:
      BJ-PI2 was a 23.08kDa single-chain polypeptide. Tryptic fragments showed highest
      homology with SVMP insularinase A from Bothrops insularis, but also with B.
      jararaca SVMP bothrojaractivase; less similarity was observed with B. jararaca
      SVMPs BJ-PI and jararafibrases II and IV. BJ-PI2 did not clot fibrinogen or rat
      citrated plasma but had alpha- and beta-fibrinogenolytic activity (inhibited by
      EDTA and 1,10-phenanthroline but not by PMSF) and attenuated coagulation after
      plasma recalcification. BJ-PI2 had fibrinolytic activity. BJ-PI2 increased the
      vascular permeability of rat dorsal skin (inhibited by 1,10-phenanthroline). BJ
      PI2 was not hemorrhagic or myonecrotic but caused migration of inflammatory
      cells. In contrast, venom was strongly hemorrhagic and myonecrotic but caused
      less infiltration of inflammatory cells. CONCLUSIONS: BJ-PI2 is a non
      hemorrhagic, non-myonecrotic, non-coagulant P-I class SVMP that may enhance
      vascular permeability and inflammatory cell migration in vivo. GENERAL
      SIGNIFICANCE: BJ-PI2 contributes to enhanced vascular permeability and
      inflammatory cell migration after envenoming, but not to venom-induced hemorrhage
      and necrosis.

PMID- 22867988
TI  - Heat shock induces a massive but differential inactivation of SUMO-specific
      proteases.
AB  - Covalent conjugation of the small ubiquitin-like modifier (SUMO) to proteins is a
      highly dynamic and reversible process. Cells maintain a fine-tuned balance
      between SUMO conjugation and deconjugation. In response to stress stimuli such as
      heat shock, this balance is altered resulting in a dramatic increase in the
      levels of SUMO conjugates. Whether this reflects an activation of the conjugation
      cascade, a decrease in the activity of SUMO-specific proteases (SENPs), or both,
      remains unknown. Here, we show that from the five human SENPs detected in HeLa
      cells (SENP1/2/3/6/7) the activities of all but one (SENP6) were largely
      diminished after 30min of heat shock. The decreased activity is not due to
      changes in their steady-state levels. Rather, in vitro experiments suggest that
      these SENPs are intrinsically heat-sensitive, a property most likely emerging
      from their catalytic domains. Heat shock inactivation seems to be a specific
      property of SENPs because numerous members of the related deubiquitinase family
      of cysteine proteases are not affected by this stress condition. Overall, our
      results suggest that SENPs are particularly sensitive to heat shock, a property
      that may be important for the adaptation of cells to this stress condition.

PMID- 22867991
TI  - A measurement-domain adaptive beamforming approach for ultrasound instrument
      based on distributed compressed sensing: Initial development.
AB  - High efficient acquisition of the sensor array signals and accurate
      reconstruction of the backscattering medium are important issues in ultrasound
      imaging instrument. This paper presents a novel measurement-domain adaptive
      beamforming approach (MABF) based on distributed compressed sensing (DCS) which
      seeks to simultaneously measure signals that are each individually sparse in some
      domain(s) and also mutually correlated with much few measurements under the
      Nyquist rate. Instead of sampling conventional backscattering signals at the
      Nyquist rate, few linear projections of the returned signal with random vectors
      are taken as measurements, which can reduce the amount of samples per channel
      greatly and makes the real-time transmission of sensor array data possible. Then
      high resolution ultrasound image is reconstructed from the few measurements of
      DCS directly by the proposed MABF algorithm without recovering the raw sensor
      signals with complex convex optimization algorithm. The simulated results show
      the effectiveness of the proposed method.

PMID- 22867989
TI  - The miR-126 regulates angiopoietin-1 signaling and vessel maturation by targeting
      p85beta.
AB  - Blood vessel formation depends on the highly coordinated actions of a variety of
      angiogenic regulators. Vascular endothelial growth factor (VEGF) and Angiopoietin
      1 (Ang-1) are both potent and essential proangiogenic factors with complementary
      roles in vascular development and function. Whereas VEGF is required for the
      formation of the initial vascular plexus, Ang-1 contributes to the stabilization
      and maturation of growing blood vessels. Here, we provide evidence of a novel
      microRNA (miRNA)-dependent molecular mechanism of Ang-1 signalling modulation
      aimed at stabilizing adult vasculature. MiRNAs are short non-coding RNA molecules
      that post-trascriptionally regulate gene expression by translational suppression
      or in some instances by cleavage of the respective mRNA target. Our data indicate
      that endothelial cells of mature vessels express high levels of miR-126, which
      primarily targets phosphoinositide-3-kinase regulatory subunit 2 (p85beta). Down
      regulation of miR-126 and over-expression of p85beta in endothelial cells inhibit
      the biological functions of Ang-1. Additionally, knockdown of miR-126 in
      zebrafish resulted in vascular remodelling and maturation defects, reminiscent of
      the Ang-1 loss-of-function phenotype. Our findings suggest that miR-126-mediated
      phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it
      strongly enhances the activities of Ang-1 on vessel stabilization and maturation.

PMID- 22867990
TI  - Relation among HPA and HPG neuroendocrine systems, transmissible risk and
      neighborhood quality on development of substance use disorder: results of a 10
      year prospective study.
AB  - BACKGROUND: Research has shown involvement of hormones of the hypothalamic
      pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the
      regulation of behaviors that contribute to SUD risk and its intergenerational
      transmission. Neighborhood environment has also been shown to relate to hormones
      of these two neuroendocrine systems and behaviors associated with SUD liability.
      Accordingly, it was hypothesized that (1) parental SUD severity and neighborhood
      quality correlate with activity of the HPG axis (testosterone level) and HPA axis
      (cortisol stability), and (2) transmissible risk during childhood mediates these
      hormone variables on development of SUD measured in adulthood. METHODS:
      Transmissible risk for SUD measured by the transmissible liability index (TLI;
      Vanyukov et al., 2009) along with saliva cortisol and plasma testosterone were
      prospectively measured in boys at ages 10-12 and 16. Neighborhood quality was
      measured using a composite score encompassing indicators of residential
      instability and economic disadvantage. SUD was assessed at age 22. RESULTS:
      Neither hormone variable cross-sectionally correlated with transmissible risk
      measured at ages 10-12 and 16. However, the TLI at age 10-12 predicted
      testosterone level and cortisol stability at age 16. Moreover, testosterone
      level, correlated with cortisol stability at age 16, predicted SUD at age 22.
      CONCLUSION: HPA and HPG axes activity do not underlie variation in TLI, however,
      high transmissible risk in childhood predicts neuroendocrine system activity
      presaging development of SUD.

PMID- 22867992
TI  - Long-term stability, biocompatibility and oral delivery potential of risperidone
      loaded solid lipid nanoparticles.
AB  - A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of
      risperidone (RISP), a poorly water-soluble drug, was designed and tested.
      Initially, lipid-RISP solubility was screened to select the best lipid for SLN
      preparation. Compritol((r))-based formulations were chosen and their long-term
      stability was assessed over two years of storage (at 25  degrees C and 4  degrees
      C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and
      encapsulation efficiency (EE) measurements. SLN shape was observed by
      transmission electron microscopy (TEM) at the beginning and end of the study. The
      oxidative potential (OP) of the SLN was measured and their biocompatibility with
      Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl
      tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were
      performed to predict the in vivo release profile and to evaluate the drug
      delivery potential of the SLN formulations, respectively. The RISP-loaded SLN
      systems were stable and had high EE and similar shape to the placebo formulations
      before and after storage. Classical Fickian diffusion was identified as the
      release mechanism for RISP from the SLN formulation. Biocompatibility and dose
      dependent RISP transport across Caco-2 cells were observed for the prepared SLN
      formulations. The viability of SLN as formulations for oral delivery of poorly
      water-soluble drugs such as RISP was illustrated.

PMID- 22867993
TI  - The repetition paradigm: enhancement of novel metaphors and suppression of
      conventional metaphors in the left inferior parietal lobe.
AB  - The neural mechanisms underlying the process of understanding novel and
      conventional metaphoric expressions remain unclear largely because the specific
      brain regions that support the formation of novel semantic relations are still
      unknown. A well established way to study distinct cognitive processes
      specifically associated with an event of interest is to repeatedly present the
      same stimulus. The aim of the current study is to examine the neural signatures
      associated with forming new metaphoric concepts by repeatedly presenting novel as
      well as conventional metaphors. In an fMRI study, 11 subjects read novel and
      conventional two-word metaphoric expressions and decided whether the expressions
      were meaningful. Prior to the study, participants were presented with half of the
      conventional metaphors and half of the novel metaphoric expressions. The present
      results revealed that whereas repeated exposure to conventional metaphors
      elicited repetition suppression within the left supramarginal gyrus, no brain
      areas showed repetition suppression effects during the repeated exposure of novel
      metaphors. However, repetition enhancement effects for novel metaphors were found
      in several brain areas including the bilateral inferior parietal gyri. These
      findings suggest that the left and right supramarginal gyri are both involved in
      the conceptualization and the storage of novel semantic relations. This study is
      important to develop theoretical accounts of the formation of conceptual
      knowledge for both familiar and novel information.

PMID- 22867994
TI  - Palliative care for advanced Parkinson disease: an interdisciplinary clinic and
      new scale, the ESAS-PD.
AB  - Palliative care provides a holistic approach to symptom relief using a
      multidisciplinary team approach to enhance quality of life throughout the entire
      course of a particular illness. The care team consists of movement disorders
      neurologist, a palliative care physician, a wound care nurse, a spiritual
      counselor and a care coordinator. Palliative care concepts were applied to a
      group of advanced Parkinson disease (PD) patients in a dedicated Palliative Care
      Clinic. METHODS: A modified Edmonton Symptom Assessment System Scale for PD (ESAS
      PD) was developed and applied to 65 PD patients at their initial consultation and
      following recommended interventions. Scores were compared to those of metastatic
      cancer patients reported in the palliative care literature. RESULTS: The ESAS-PD
      scores significantly improved after the interventions (56 and 40 respectively, p
      = 0.0001). The most improved items were constipation, dysphagia, anxiety, pain
      and drowsiness. ESAS-PD scores were not significantly different from metastatic
      cancer patients' ESAS scores. CONCLUSIONS: ESAS-PD is a quick, effective scale
      for assessment of late stage PD symptoms. Scores are sensitive to intervention,
      and therefore have potential clinical utility for physicians and other healthcare
      providers. Advanced PD patients have a similar degree of symptoms as metastatic
      cancer patients, respond to treatment in a similar way, and therefore should have
      access to palliative care services.

PMID- 22867995
TI  - Molecular inversion probes: a novel microarray technology and its application in
      cancer research.
AB  - The molecular inversion probe (MIP) assay technology was originally developed for
      single nucleotide polymorphism (SNP) genotyping, but has subsequently been used
      for identifying other types of genetic variation including focal insertions and
      deletions, larger copy number alterations (CNAs), loss of heterozygosity (LOH),
      and most recently, for somatic mutation detection. The assay requires as little
      as 75 ng of genomic DNA and has been shown to perform well with highly degraded
      DNA, such as that from formalin-fixed paraffin-embedded (FFPE)-preserved samples
      from 20 years ago or older. Central to the MIP assay technology are the padlock
      probes that hybridize to the DNA target of interest before polymerase chain
      reaction amplification, leading to high assay specificity. As outlined in this
      review, the MIP assay has enabled new discoveries and a deeper understanding of
      the molecular basis of cancer and its various disease subtypes. The use of novel
      genomic technology such as MIPs on clinically archived FFPE samples has the
      potential to lead to more accurate disease diagnosis, prognosis, and novel
      therapeutic intervention. This review describes the initial history of MIP
      technology, details of the MIP assay, its current analysis techniques, and recent
      publications related to this novel platform.

PMID- 22867996
TI  - HELIOS-BCL11B fusion gene involvement in a t(2;14)(q34;q32) in an adult T-cell
      leukemia patient.
AB  - To provide fundamental insights into the leukemogenesis of adult T-cell
      leukemia/lymphoma (ATLL), we performed a molecular analysis of the chromosomal
      abnormalities in one ATLL case with a novel reciprocal translocation:
      t(2;14)(q34;q32). Using fluorescence in situ hybridization with cosmid probes
      derived from the 14q32 region, we characterized the rearranged 14q32 allele.
      Molecular cloning of the breakpoint revealed that the reciprocal translocation
      fused the 5' proximal region of the B-cell lymphoma 11B (BCL11B) gene segment (on
      14q32) to the third intron of the HELIOS gene (on 2q34). Reverse transcription
      polymerase chain reaction analysis of the leukemia cells revealed that a
      substantial level of the HELIOS-BCL11B fusion mRNA was expressed relative to the
      level of wild-type (WT)-BCL11B derived from the intact allele. In contrast, an
      aberrant HELIOS isoform was detected at a low level of expression compared to the
      expression of normal HELIOS isoforms. Functional analysis of the HELIOS-BCL11B
      fusion protein revealed reduced transcriptional suppression activity compared to
      that of the WT-BCL11B due to the loss of the N-terminal friend of GATA-repression
      motif, which functions as a metastasis-associated protein 2 binding site. We also
      found abnormal subnuclear localization of the ectopically expressed fusion
      protein compared to the localization of WT-BCL11B to subnuclear speckles in
      HEK293T cells. Our results suggest that dysfunction of the BCL11B gene plays an
      important role in the development of ATLL.

PMID- 22867997
TI  - A cytogenetic study of 397 consecutive acute myeloid leukemia cases identified
      three with a t(7;21) associated with 5q abnormalities and exhibiting similar
      clinical and biological features, suggesting a new, rare acute myeloid leukemia
      entity.
AB  - The RUNX1 gene is implicated in numerous chromosomal translocations that occur in
      acute myeloid leukemia (AML) and result in chimeric genes. In this study, 397
      consecutive AML cases were analyzed using RUNX1 fluorescence in situ
      hybridization (FISH) probes. Three cases of the recently described translocation,
      t(7;21)(p22;q22), were identified, which expressed RUNX1-USP42 (ubiquitin
      specific protease 42) fusion transcripts, associated with 5q abnormalities and
      hyperploidy. These cases displayed homogeneous morphological features (including
      phagocytosis) and aberrantly expressed CD56 and CD7 lymphoid antigens. Although
      very few data are available from previously reported cases, when these features
      are present, a detailed chromosomal analysis, including hybridization with RUNX1
      FISH probes, should be performed at diagnosis to recognize chromosomal
      abnormalities. Additional cases of t(7;21) positive AML should be evaluated to
      characterize this potentially rare AML entity in greater detail.

PMID- 22867998
TI  - A polymorphism at the miR-502 binding site in the 3' untranslated region of the
      SET8 gene is associated with the risk of epithelial ovarian cancer.
AB  - MicroRNAs (miRNAs) bind to the 3' untranslated regions (UTRs) of messenger RNAs,
      where they interfere with the translation of genes that regulate cell
      differentiation, apoptosis, and tumorigenesis. SET8 reportedly methylates TP53
      and regulates genomic stability. We analyzed a single nucleotide polymorphism
      (rs16917496) within the miR-502 mRNA seed region of the 3' UTR of SET8 in Chinese
      epithelial ovarian cancer (EOC) patients. The SET8 CC genotype was associated
      with a decreased risk of EOC in this case-control study. The analysis of genetic
      polymorphisms in miRNA binding sites may help identify subgroups of populations
      that are at high risk for EOC.

PMID- 22867999
TI  - A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a
      model of the Warburg effect in cancer.
AB  - The role of energy deregulation and altered/adapted metabolism in tumor cells is
      an increasingly important issue in understanding cancer. Hereditary
      leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive form of RCC
      characterized by germline mutation of fumarate hydratase (FH), followed by
      somatic loss of the remaining wild-type allele and known to be a highly
      metastatic and lethal malignancy compared to other RCCs. The intrinsic loss of
      normal tricarboxylic acid (TCA) cycle presumably aids tumorigenesis due to the
      necessary metabolic alterations required and the enforced dependence on
      glycolysis derived energy, mimicking the Warburg effect. Thus, there is
      considerable utility in establishing a preclinical cell model from these tumors
      to study energy metabolism deregulation, as well as developing new targeted
      therapeutic approaches for TCA cycle enzyme-deficient cancers. Here, we describe
      a new immortalized cell line, UOK268, derived from a patient's primary HLRCC
      associated kidney cancer. This represents the first primary renal cell line to
      model TCA cycle gene loss and provides a perfect partner cell line to our
      previously described metastasis-derived HLRCC-associated cell line, UOK262. We
      identified a novel germline FH missense mutation, p.His192Asp, and the subsequent
      loss of heterozygosity in UOK268. The UOK268 cell line expressed mutant FH
      protein, which localized to the mitochondria, but with loss of almost all
      catalytic activity. The UOK268 cells had severely compromised oxidative
      phosphorylation and increased glycolytic flux. Ingenuity pathways analysis of
      human mitochondria-focused cDNA microarray (hMitChip3) gene chip data confirmed
      the altered mRNA expression patterns of genes involved in several important
      pathways, such as lipid metabolism, apoptosis, and energy production/glycolysis.
      UOK268 provides a unique model of a primary cell line demonstrating an enforced,
      irreversible Warburg effect and, combined with UOK262, provides a unique in vitro
      preclinical model for studying the bioenergetics of the Warburg effect in human
      cancer.

PMID- 22868001
TI  - When are apparently non-clonal abnormalities in bone marrow chromosome studies
      actually clonal?
AB  - The observation of an apparently non-clonal abnormal cell in a cytogenetic study
      for a hematologic neoplasm opens the possibility of a small, or slowly
      proliferating, abnormal clone. Many laboratories analyze additional cells or
      reflex to fluorescence in situ hybridization (FISH) to evaluate this possibility
      further. In a retrospective study of 500 cases with a non-clonal abnormal cell
      identified in a 20-cell analysis, we found that the benefit of additional
      metaphase analysis was limited to specific categories of abnormal karyotypes,
      including those with a complex karyotype or a classic abnormality known to be a
      recurring finding in hematologic neoplasms, and excluding all other categories.

PMID- 22868002
TI  - Molecular genetic characterization of the 11q13 breakpoint in a desmoplastic
      fibroma of bone.
AB  - Desmoplastic fibroma (DFB) is a benign primary bone tumor that usually occurs in
      adolescents and young adults. The genetic information on DFB is very limited. We
      here present cytogenetic, fluorescence in situ hybridization and single
      nucleotide polymorphism array findings in a case that had a rearrangement
      involving chromosomes 11 and 19 at G-banding analysis. The results showed that
      the breakpoint in 11q was different from that in desmoplastic fibroblastomas, and
      a segment containing five genes was hemizygously deleted from 11q13.

PMID- 22868000
TI  - Molecular inversion probe analysis detects novel copy number alterations in Ewing
      sarcoma.
AB  - Ewing sarcoma (ES) is the second most common bone tumor in children and young
      adults, with dismal outcomes for metastatic and relapsed disease. To better
      understand the molecular pathogenesis of ES and to identify new prognostic
      markers, we used molecular inversion probes (MIPs) to evaluate copy number
      alterations (CNAs) and loss of heterozygosity (LOH) in formalin-fixed paraffin
      embedded (FFPE) samples, which included 40 ES primary tumors and 12 ES metastatic
      lesions. CNAs were correlated with clinical features and outcome, and validated
      by immunohistochemistry (IHC). We identified previously reported CNAs, in
      addition to SMARCB1 (INI1/SNF5) homozygous loss and copy neutral LOH. IHC
      confirmed SMARCB1 protein loss in 7-10% of clinically diagnosed ES tumors in
      three separate cohorts (University of Utah [N = 40], Children's Oncology Group [N
      = 31], and University of Michigan [N = 55]). A multifactor copy number (MCN)
      index was highly predictive of overall survival (39% vs. 100%, P < 0.001). We
      also identified RELN gene deletions unique to 25% of ES metastatic samples. In
      summary, we identified both known and novel CNAs using MIP technology for the
      first time in FFPE samples from patients with ES. CNAs detected by microarray
      correlate with outcome and may be useful for risk stratification in future
      clinical trials.

PMID- 22868003
TI  - Hyperhaploid plasma cell myeloma.
AB  - Conventional cytogenetics shows chromosome abnormalities in one third of plasma
      cell myeloma (PCM) cases. These chromosome abnormalities can be used to divide
      PCM into two major aneuploidy groups: hyperdiploid PCM and non-hyperdiploid PCM.
      Hypodiploid PCM is associated with a poor prognosis relative to other ploidy
      groups. Hypodiploid karyotypes usually have a modal number of 40 or more. Near
      haploidy is a rare phenomenon in PCM. We present three cases of PCM with
      hyperhaploid karyotypes from our laboratory, and review three cases reported in
      the literature. All six cases had modal numbers ranging from 27 to 33. Two copies
      of chromosomes 3, 7, 9, 11, 15, 18 and 19 were present in all cases. Five of the
      six cases had two copies of chromosome 21 and four of the six cases had two
      copies of chromosome 5. The three patients studied at our laboratory had
      aggressive disease and a short survival but the small number of cases makes
      predicting outcome in this group difficult. The consistent pattern of cytogenetic
      abnormalities present in these cases suggests that hyperhaploidy may be a
      distinct cytogenetic entity in PCM.

PMID- 22868004
TI  - Synchronous detection of miRNAs, their targets and downstream proteins in
      transferred FFPE sections: applications in clinical and basic research.
AB  - After discovering new miRNAs, it is often difficult to determine their targets
      and effects on downstream protein expression. In situ hybridization (ISH) and
      immunohistochemistry (IHC) are two commonly used methods for clinical diagnosis
      and basic research. We used an optimized technique that simultaneously detects
      miRNAs, their binding targets and corresponding proteins on transferred serial
      formalin fixed paraffin embedded (FFPE) sections from patients. Combined with
      bioinformatics, this method was used to validate the reciprocal expression of
      specific miRNAs and targets that were detected by ISH, as well as the expression
      of downstream proteins that were detected by IHC. A complete analysis was
      performed using a limited number of transferred serial FFPE sections that had
      been stored for 1-4 years at room temperature. Some sections had even been
      previously stained with H&E. We identified a miRNA that regulates epithelial
      ovarian cancer, along with its candidate target and related downstream protein.
      These findings were directly validated using sub-cellular components obtained
      from the same patient sample. In addition, the expression of Nephrin (a podocyte
      marker) and Stmn1 (a recently identified marker related to glomerular
      development) were confirmed in transferred FFPE sections of mouse kidney. This
      procedure may be adapted for clinical diagnosis and basic research, providing a
      qualitative and efficient method to dissect the detailed spatial expression
      patterns of miRNA pathways in FFPE tissue, especially in cases where only a small
      biopsy sample can be obtained.

PMID- 22868005
TI  - How does the 50/500 rule apply to MVPs?
AB  - The 50/500 rule has been used as a guiding principle in conservation for
      assessing minimum viable effective population size (N(e)). There is much
      confusion in the recent literature about how the 500 value should be applied to
      assess extinction risk and set priorities in conservation biology. Here, we argue
      that the confusion arises when the genetic basis for a short-term N(e) of 50 to
      avoid inbreeding depression is used to justify a long-term N(e) of 500 to
      maintain evolutionary potential. This confusion can result in misleading
      conclusions about how genetic arguments alone are sufficient to set minimum
      viable population (MVP) thresholds for assessing the extinction risk of
      threatened species, especially those that emphasize that MVPs should be in the
      thousands to maintain evolutionary potential.

PMID- 22868006
TI  - Flexible bronchoscopy during mechanical ventilation in the prone position to
      treat acute lung injury.
AB  - In patients with severe acute lung injury (ALI) or acute respiratory distress
      syndrome (ARDS) the prone position has been shown to improve survival of patients
      who are severely hypoxemic with an arterial oxygen tension to inspiratory oxygen
      fraction ratio (PaO(2)/FiO(2))<100. In those patients tracheobronchial toilette
      is crucial in preventing or treating airways obstructed by secretions and
      deterioration of oxygenation. Flexible fiberoptic bronchoscopy is widely
      recognized as an effective technique to perform bronchial toilette in the
      intensive care unit (ICU). Flexible bronchoscopy performed during prone
      mechanical ventilation in two cardiosurgical patients who developed ALI after
      complex surgery, proved feasible and safe and helped to avoid undesirable earlier
      cessation of prone mechanical ventilation. However decision making about
      bronchoscopy in severe hypoxia should be even more cautious than in the supine
      patient, as dangerous delay in resuscitation manoeuvres due to postponed
      switching the patient to the supine position should always be prevented.

PMID- 22868007
TI  - Participation, socioeconomic status and group or individual counselling
      intervention in individuals at high risk for type 2 diabetes: one-year follow-up
      study of the FIN-D2D-project.
AB  - AIMS: To describe socioeconomic characteristics of participants and their effect
      on uptake and completion of the implementation project (FIN-D2D) for the National
      Type 2 Diabetes Prevention Programme. Furthermore, to assess the effectiveness of
      individual vs. group intervention during one-year follow-up. METHODS: At
      baseline, 2820 men and 5764 women aged <65 years participated in the non
      randomized implementation project in primary health care setting; one-year follow
      up was available for 1067 men and 2122 women. Socioeconomic status included
      education and occupation. Interventions were individual and/or group-based. The
      changes in cardiovascular risk factors and glucose tolerance were used as
      measures of the effectiveness of intervention. RESULTS: 68.4% of the men and
      69.8% of the women participated in some of the intervention modalities offered.
      Low education and not working were related to active participation in the
      intervention in men. 88.2% of men and 76.1% of women selected the individual
      instead of group intervention. The effectiveness of individual vs. group
      interventions did not differ, except for minor changes in systolic blood pressure
      in women and glucose tolerance in men. CONCLUSIONS: Socioeconomic status
      modulated participation in interventions. Both types of intervention worked
      equally well, but participation in group intervention was low.

PMID- 22868008
TI  - Two neutral thermostable cellulases from Phialophora sp. G5 act synergistically
      in the hydrolysis of filter paper.
AB  - Two novel cellulase genes, cbh6A and egGH45, were cloned from Phialophora sp. G5
      and successfully expressed in Pichia pastoris. The putative polypeptide of CBH6A
      consists of a family 1 CBM and a catalytic domain of glycosyl hydrolase family 6
      cellobiohydrolases, while deduced EgGH45 only contains a catalytic domain of
      family 45 endoglucanases. CBH6A and EgGH45 were optimally active at pH 7.0 and 65
      degrees C, and pH 6.0 and 60 degrees C, respectively. Both enzymes exhibited high
      activities and stabilities over a wide pH range and had good thermostability at
      70 degrees C. CBH6A and EgGH45 had significant resistance to SDS (10mM),
      remaining 35% and 54% activities, respectively. These enzymes had synergic effect
      on the hydrolysis of filter paper, showing the highest efficiency in the ratio of
      CBH6A to EgGH45 at 80:20. The properties make this enzyme combination potential
      for application in textile and detergents industries.

PMID- 22868009
TI  - Bacterial polymer production using pre-treated sludge as raw material and its
      flocculation and dewatering potential.
AB  - Sterilization, alkaline-thermal and acid-thermal treatments were applied to
      different sludge solids concentrations (17.0; 22.4; 29.8; 37.3; 44.8 g/L,
      respectively) and the pre-treated sludge was used as raw material for Serratia
      sp.1 to produce extracellular polymeric substances (EPS). After 72 h of
      fermentation, total EPS of 2.3 and 3.4 g/L were produced in sterilized and
      alkaline-thermal treated sludge as compared to that of 1.5 g/L in acid-thermal
      treated sludge. Lower EPS were produced at relatively higher solids
      concentrations (37.3; 44.8 g/L). Broth, crude forms of capsular and slime EPS
      were extracted from fermented broths and used as conditioning agents by combining
      with 150 mg of Ca(2+)/L of kaolin suspensions. Maximum flocculation activity of
      79.1% and increased dewatering by 52.2% was achieved using broth and crude
      capsular EPS, respectively. The results demonstrated that EPS having high
      flocculating capability could be produced using wastewater sludge as sole raw
      material.

PMID- 22868010
TI  - Nanomedicine.

PMID- 22868011
TI  - Serum cholesterol: could it be a sixth parameter of Child-Pugh scoring system in
      cirrhotics due to viral hepatitis?
AB  - OBJECTIVE: To determine the association of serum cholesterol levels with Child
      Pugh class in patients with decompensated chronic liver disease due to viral
      hepatitis. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF
      STUDY: Jinnah Postgraduate Medical Centre, Karachi, Medical Unit-III, Ward-7 from
      June to December 2010. METHODOLOGY: Consecutive patients attending outpatient
      department or admitted in medical unit III were eligible if they had a diagnosis
      of cirrhosis secondary to viral hepatitis. Patients were excluded if alcoholic,
      diabetic, hypertensive, or with non-alcoholic fatty liver disease, autoimmune,
      metabolic, cardiovascular, cerebrovascular or kidney diseases and recent use of
      lipid-regulating drugs. Serum lipid profile was determined after an overnight
      fast of 12 hours. On the basis of serum total cholesterol, patients were divided
      into four groups; Group I with serum total cholesterol 2 100 mg/dl, Group II with
      level of 101-150 mg/dl, Group III with level of 151-200 mg/dl and Group IV with
      serum total cholesterol level of > 200 mg/dl. Hepatic dysfunction was categorized
      according to Child-Pugh scoring system. Chi-square and Spearman's correlation
      testing with p < 0.05 was accepted as significant. RESULTS: One hundred and
      fourteen patients met the inclusion criteria with a mean age of 40.32 +/- 13.59
      years. Among these 32 were females (28.1%) while 82 were males (71.9%). According
      to Child-Pugh class; 34 patients (29.8%) presented with Child-Pugh class A, 34
      (29.8%) in class B and 46 (40.4%) were in class C. Serum cholesterol (total) and
      triglycerides had significant association with Child-Pugh class (p = 0.0001 and p
      = 0.004 respectively) suggesting that as severity of liver dysfunction increases;
      serum cholesterol and triglycerides levels decrease. Results also revealed that
      males were significantly more hypocholesterolemic than females (p = 0.006).
      CONCLUSION: Hypocholesterolemia is a common finding in decompensated chronic
      liver disease and has got significant association with Child-Pugh class. It may
      increase the reliability of Child-Pugh classification in assessment of severity
      and prognosis in chronic liver disease patients.

PMID- 22868012
TI  - Active disease in chronic hepatitis C patients with normal alanine
      aminotransferase.
AB  - OBJECTIVE: To quantify liver damage using Metavir score, in chronic hepatitis C
      patients having normal alanine aminotransferase (ALT) to determine active disease
      requiring treatment. STUDY DESIGN: An analytical study. PLACE AND DURATION OF
      STUDY: Pakistan Medical Research Centre, JPMC, Karachi, from January 2007 -
      December 2010. METHODOLOGY: Patients suffering from hepatitis C with positive
      PCR, having persistently normal ALT on 3 separate occasions over a 6 months
      period and also having normal platelets and albumin were included in the study.
      After written consent, all patients underwent a liver biopsy and the degree of
      damage was assessed using Metavir scoring system. RESULTS: A total of 99 patients
      suffering from chronic HCV were included in the study. A majority of the patients
      (55.6%) were females. Using Metavir score, minimal fibrosis of 2 1 was seen in
      majority (78.8%) of the patients. Only 21.2% patients had fibrosis score 3 2,
      with 16 (47.1%) of these also having inflammatory score 3 2 (p < 0.001). The age
      of patients (mean 38.1 +/- 10.2 years) had a significant association with the
      severity of liver damage (p < 0.001) as compared to younger age group (mean 33.1
      + 9.8 years). CONCLUSION: A large proportion of patients with normal ALT have
      insignificant fibrosis indicating non active disease and thus questions the
      blanket use of interferon in all HCV RNA cases. It is strongly recommended that a
      liver biopsy should be done in all cases with normal ALT before deciding
      antiviral therapy.

PMID- 22868013
TI  - MELD score: utility and comparison with King's College criteria in non
      acetaminophen acute liver failure.
AB  - OBJECTIVE: To compare Model for End-stage Liver Disease Score (MELD Score, MS)
      and King's College Hospital (KCH) criteria for finding correlation of mortality
      in non-acetaminophen induced acute liver failure (NAI-ALF). STUDY DESIGN: An
      analytical cross-sectional study. PLACE AND DURATION OF STUDY: The Aga Khan
      University Hospital, Karachi, from 2005 to 2007. METHODOLOGY: The study included
      patients with NAI-ALF. KCH criteria were labelled as good and bad prognosis
      groups. MELD score were calculated by using the MELD calculator. ROC was plotted
      and sensitivity analysis was done. ETA was used to see correlation between MELD
      and KCH. RESULTS: Ninety-one patients with mean age of 32.5 + 16.3 years were
      studied; 49 were males (54%). Out of these, 57 patients died (63%); two leading
      causes of non-acetaminophen induced acute liver failure (NAI-ALF) were hepatitis
      hepatitis B virus (HBV) (n = 30, 33%) followed by hepatitis E virus in (n = 23,
      25.3%). According to King's College Hospital (KCH) criteria, 50 patients (88%)
      who died had bad prognosis and 24 patients (70.6%) who survived had good
      prognosis. The ROC determined MELD score of 32 was the best predictor of
      mortality with sensitivity and specificity of 79% and 71%, respectively and
      positive predictive value (PPV) and negative predictive values (NPV) of 82% and
      67% respectively. There was significant association between mortality and bad
      prognosis according to KCH criteria (p < 0.001). Overall mean MELD score (MMS)
      was 35.35 + 8.64. MMS on admission was 38 + 7.32 in patients who died and 30.7 +
      8.77 in those who survived (p = < 0.001). MMS correlated equally with KCH
      criteria (ETA = 0.52). CONCLUSION: The admission MELD score has an excellent
      utility and correlates equally with KCH criteria for mortality in NAI- ALF.

PMID- 22868014
TI  - Visual outcome of unilateral traumatic cataract.
AB  - OBJECTIVE: To evaluate the visual outcome of a series of patients presenting with
      unilateral traumatic cataract. STUDY DESIGN: Observational study. PLACE AND
      DURATION OF STUDY: Ophthalmology Department, Liaquat University Hospital,
      Hyderabad, from July 2007 to June 2010. METHODOLOGY: Analysis included data of 41
      patients (31 males and 10 females) with unilateral traumatic cataract. Data
      regarding demographics, causative agent, clinical course and outcome in terms of
      best corrected visual acuity (BCVA) was retrieved from the patients' files in
      hospital record. Data was expressed as frequencies, percentages, mean and
      standard deviation. RESULTS: There was a male predilection with a male to female
      ratio of 3.1:1. The age group more frequently affected was 5 - 14 years (58.5%).
      Commonest causative agent was trauma with wooden stick in 13 eyes (31.7%)
      followed by thorn in 9 eyes (22%) and stone in 7 eyes (17.1%). Pre-existing
      posterior capsular defects were observed intraoperatively in 6 eyes. Posterior
      capsular opacification was evident in 10 eyes (24%). Best corrected visual acuity
      of 6/18 or more at 6 months was achieved in 29 eyes (70.8%). Duration between
      injury and cataract surgery did not affect the final visual outcome of traumatic
      cataract patients. CONCLUSION: Patients with traumatic cataract if managed
      appropriately can have best possible visual outcome. Young males are commonly
      affected. Taking protective measures in sports and work as well as patient
      education can avoid ocular trauma and traumatic cataract formation.

PMID- 22868015
TI  - Characteristics and pattern of rhegmatogenous retinal detachment in pakistan.
AB  - OBJECTIVE: To determine the presenting characteristics of rhegmatogenous retinal
      detachment (RRD) in a consecutive series of Pakistani patients. STUDY DESIGN:
      Case series. PLACE AND DURATION OF STUDY: Layton Rahmatullah Benevolent Trust
      (LRBT), Lahore, from June 2010 to October 2011. METHODOLOGY: A total of 107 eyes
      underwent RRD surgery. Detailed diagrams were drawn pre-operatively for all.
      Other recorded details included, bio-data, age, gender, visual acuity,
      autorefractometery, predisposing risk factors, lens state and duration of
      symptoms. The data was analyzed with respect to age and gender distribution,
      frequency of various risk factors for RRD, duration of RRD and its various
      presenting characteristics. RESULTS: Mean age of the patients were 33.1 +/- 1.5
      years, 85% were males. Bilateral RRD was discovered in 2.8% patients. No
      identifiable risk factor for RRD was present in 28%, while in rest of the 72%
      eyes, the commonest risk factors were intraocular surgery, trauma and peripheral
      myopic degeneration in decreasing order of frequency. There were 70.1% phakic,
      23.4% pseudophakic and 6.5% aphakic eyes. Majority (93.5%) presented with macula
      off detachment. There was an overall average time lapse of 97.24 +/- 16.95 days
      between presenting and first occurrence of symptoms. In 31.8% of eyes no break
      could be found pre-operatively, while 38.3% had 1 and 29.9% eyes had 3 2 breaks.
      Majority of the primary breaks were horse-shoe tears (42.1%). Total RRD was found
      in 35.5% eyes. Infero-temporal and supero-temporal were the most frequently
      involved quadrants (93.5% and 86.9% respectively). CONCLUSION: Intraocular
      surgery, trauma and lattice degeneration in myopia are established common risk
      factors for RRD. These patients deserve meticulous fundus examination with
      indentation indirect ophthalmoscopy by trained professionals.

PMID- 22868016
TI  - Post-tonsillectomy pain and vomiting:role of pre-operative steroids.
AB  - OBJECTIVE: To evaluate the effects of a single pre-operative dose of
      dexamethasone with the frequency of postoperative vomiting and severity of throat
      pain in children undergoing electrocautery tonsillectomy under standard general
      anaesthesia. STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF
      STUDY: ENT Department, Combined Military Hospital, Kharian, from January to
      December 2010. METHODOLOGY: Children of either gender aged between 4 - 12 years,
      undergoing tonsillectomy were divided into two groups of 50 each. One group was
      selected to receive dexamethasone 0.5 mg/kg (maximum of 8 mg); the second group
      was given equivalent volume of saline, pre-operatively. The frequency of early
      and late vomiting was assessed postextubation. Mean time of first oral intake in
      minutes after extubation and mean score of postoperative throat pain were
      compared in both groups. Severity of throat pain was monitored by Visual Analogue
      Scale (VAS) score 0-10 after 4,8,12 and 24 hours of extubation. RESULTS:
      Dexamethasone group showed significantly less postoperative early vomiting (12%,
      n = 6) as compared to placebo (30%, n = 15) group (p < 0.05). The mean time of
      first oral intake was earlier in the dexamethasone group (4 hours and 16 minutes
      postextubation), while in saline group it was 5 hours and 20 minutes (p < 0.001).
      Pain score was also significantly lower and swallowing was less painful in
      patients after 4,8,12 and 24 hours in dexamethasone group. Pain score on the
      average was 0.8 - 1.2 factors less in dexamethasone group than in saline group in
      first 24 hours on a VAS score of 1 -10. CONCLUSION: Pre-operative intravenous
      dexamethasone reduced postoperative vomiting and pain significantly in children
      undergoing electrocautery tonsillectomy.

PMID- 22868017
TI  - Management of impacted urethral stones in children.
AB  - OBJECTIVE: To find out the clinical presentation, site of impaction, management
      and outcome of children presenting with urinary retention due to urethral stone.
      STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Surgical Unit B of
      National Institute of Child Health (NICH), Karachi, from April 2009 to January
      2010. METHODOLOGY: All the patients under the age of 12 years, who presented with
      urinary retention due to impacted urethral stones were included. Urinary
      retention due to other causes like trauma, stricture, pelvic masses etc. were
      excluded. Diagnosis was made on clinical examination (palpable stone in penile
      urethra) and with the help of radiology. Surgical procedure was tailored
      according to the site of impaction in urethra. All stones were sent for chemical
      analysis and patients were followed in Nephrology OPD (stone clinic) for further
      work-up. RESULTS: There were a total of 19 patients with mean age of 3.94 +/-
      2.27 years. All were males. Twelve patients (63.1%) had stones impacted in
      anterior urethra while 7 (36.9%) were found in posterior urethra. Stones in
      penile urethra were removed in emergency either by meatotomy (when impacted at
      urethral meatus, n = 3) or following initial supra-pubic decompression of urinary
      bladder (using wide bore cannula) by urethrolithotomy (n = 6). Stones in bulbous
      (n = 3) and posterior urethral (n = 7) locations were pushed back into bladder
      and later removed on elective list by supra-pubic vesicolithotomy. No patient had
      proximal urinary tract calculi on further work-up. All patients remained well
      except one who developed retention of urine after a week of discharge. He had
      urinary tract infection and was treated with antibiotics. All the stones were of
      calcium oxalate type. CONCLUSION: Urethral stones must be kept in differential
      diagnosis in a child who presents with acute urinary retention. Clinical
      examination can identify causes in significant number of cases. Simple procedures
      like meatotomy, supra-pubic bladder decompression and urethrolithotomy can
      relieve the misery in these children.

PMID- 22868018
TI  - Periodontal disease in type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the periodontal status in well controlled and poorly
      controlled type 2 diabetic patients compared with normal healthy individuals.
      STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY:
      Diabetes Management Centre, Services Hospital, Lahore, from November 2009 to
      January 2010. METHODOLOGY: Forty well controlled and forty poorly controlled type
      2 diabetic subjects having good oral hygiene (scored according to simplified oral
      hygiene index) were compared with a control group of forty normal healthy
      individuals. Probing depth (PD), gingival recession (GR), and attachment loss
      (AL) were recorded to obtain the periodontal status of each tooth, using a
      Michigan probe "0" with Williams marking. Glycemic control was evaluated by
      glycated Hb value. Using ANOVA and independent sample t-test, mean probing depth
      and attachment loss in each tooth type (incisors, canines, premolars and molars)
      were compared. RESULTS: Mean age of diabetic subjects was 58.86 +/- 6.21 years
      and that of control group was 56.92 +/- 6.91 years; 60% were females. Probing
      depth was greater in patients with poorly controlled diabetes compared to well
      controlled diabetic patients and non-diabetic controls (4.21 mm vs. 3.72 mm and
      2.93 mm respectively, p < 0.001). Attachment loss also increased in poorly
      controlled diabetes (p < 0.001) compared to the control group and well controlled
      diabetes, however, the difference was not statistically significant when
      comparing well controlled to the control group (p > 0.05). Number of sites and
      mean percentage of sites with attachment loss of 3 4 and 3 6 mm was also
      significantly higher in poorly controlled diabetes compared to the control group
      (p < 0.05 and p < 0.001 respectively). CONCLUSION: Periodontal status as
      estimated by probing depth and degree of attachment loss deteriorates
      significantly with poor glycemic control in diabetes.

PMID- 22868019
TI  - Mandibular reconstruction using osteocutaneous radial forearm flap.
AB  - OBJECTIVE: To describe the use of radial forearm osteocutaneous free flap in
      complex mandibular reconstruction. STUDY DESIGN: A case series. PLACE AND
      DURATION OF STUDY: Combined Military Hospital, Rawalpindi, from January 1998 to
      January 2008. METHODOLOGY: Patients having a small bony component and a large
      soft tissue mandibular defect requiring reconstruction were selected. These
      defects include composite through-and-through defects of the cheek in the
      retromolar trigone, small lateral bony defects with large intra and extra oral
      soft tissue defects and small central bony defects with large extra oral tissue
      loss. Radial forearm osteocutaneous free flap was employed. Complications and
      graft acceptance were determined at follow-up. RESULTS: Patients were followed-up
      for an average period of 28 months. Complications occurred in 8 patients. Wound
      infection and partial wound dehiscence were the most common complication observed
      in 3 patients. Non-union at recipient site was seen in 2 patients. Flap donor
      site healed uneventfully in all patients with no fractures at the donor site.
      CONCLUSION: The radial forearm osteocutaneous flap covers oromandibular defects
      with large intra-oral and extra oral soft tissue losses. Lateral and anterior
      mandibular defects were reconstructed satisfactorily in our series.

PMID- 22868020
TI  - Coexistence of multiple omphalomesenteric duct anomalies.
AB  - The omphalomesenteric duct is an embryonic structure which connects the yolk sac
      to the midgut. The omphalomesenteric duct attenuates between the 5th and 9th week
      of gestation. Failure of the omphalomesenteric duct involution, either partial or
      complete, results in various omphalomesenteric duct remnants including Meckel's
      diverticulum, patent vitelline duct, fibrous band, sinus tract, umbilical polyp
      and cyst. Omphalomesenteric duct remnants are present in 2% of the population but
      related diseases have seldom been reported in adults. The simultaneous presence
      of sinus tract, omphalomesenteric cyst, fibrous ligament and Meckel's
      diverticulum has, according to authors' knowledge, never been reported. We
      present a case of a 23 years old male with persisting umbilical discharge for 2
      years in whom there was coexistence of the above mentioned anomalies of the
      omphalomesenteric duct.

PMID- 22868021
TI  - Pulmonary tuberculosis with neuromyelitis optica: an uncommon association of a
      common disease.
AB  - Systemic tuberculosis has been reported with varying neurological manifestations
      like meningitis, tuberculomas, myositis and neuropathy. Neuromyelitis optica
      (NMO) is a well known neurological entity which has been described in association
      with several systemic disorders like systemic lupus erythematosis, diabetes
      mellitus, hypothyroidism, exposure to insecticides etc. However, only a few cases
      of NMO have been reported in association with Mycobacterium tuberculosis. Here,
      we report a case of pulmonary tuberculosis in association with NMO to highlight
      the under-reported association of NMO with pulmonary tuberculosis presenting in a
      peculiar anatomical fashion i.e. longitudinal myelitis with predominant posterior
      column involvement.

PMID- 22868022
TI  - Pneumorrhachis of thoracic spine after gunshot wound.
AB  - Air in the spinal canal (Pneumorrhachis) is a rare complication of traumatic
      spinal injuries reported at various levels of the spinal canal. Pneumorrhachis
      resolves spontaneously most of the times. Rarely, it may cause cord compression.
      It is important to rule out potentially serious causes like basilar skull
      fracture, injury to lungs, mediastinum, mastoid air cells, frontal sinuses or
      intestine. We present a case of pneumorrhachis in a young soldier who sustained
      gunshot wound in neck, resulting in spinal cord injury, He was managed
      conservatively and pneumorrhachis resolved spontaneously without complications.
      Pathogenesis along with review of relevant literature is presented.

PMID- 22868023
TI  - Congenital osteolytic dural fibrosarcoma presenting as a scalp swelling.
AB  - An extremely rare case of congenital dural fibrosarcoma is reported in a 2 months
      old child who presented with scalp swelling since birth. CT scan revealed an
      osteolytic lesion compressing the underlying atrophic brain. Tumour was
      completely excised and duroplasty was done with a patch graft. Postoperative CSF
      leak was managed with aspirations and lumbar puncture.

PMID- 22868024
TI  - Healing of cornea following an electric burn.
AB  - Electrical injuries have become a significant health problem in developing
      countries because of increase in access to electricity in the last few decades
      and lack of adequate safety measures. Electrical injuries of eyes are relatively
      uncommon. A case report of a rapid and complete corneal healing accompanied by
      satisfactory visual recovery after an electric burn event in a 20-year-old male
      is reported. The patient had accidental exposure to high voltage live wire while
      he was repairing it, resulting in severe ocular and superficial body burn. He was
      not wearing any protective equipment at the time of injury. On examination, the
      best-corrected visual acuity was counting fingers in the left eye with severe
      corneal epithelial loss and diffuse corneal oedema. The patient was treated
      medically, with a rapid corneal healing and resolution of oedema over the next
      few days. Visual acuity in the worse eye (left) improved to 20/25 from counting
      fingers.

PMID- 22868025
TI  - Pheochromocytoma: a rare cause of childhood hypertensive encephalopathy.
AB  - Pheochromocytomas are rare neuroendocrine tumours of chromaffin tissues. They are
      catecholamine secreting tumours which cause severe hypertension and other
      systemic disturbances. Of all the causes of childhood hypertension,
      pheochromocytoma constitutes less than 1%. We report the case of a 12 years old
      child who presented with hypertensive encephalopathy, confirmed histologically to
      be secondary to pheochromocytoma, and cured with meticulous critical care and
      surgical resection.

PMID- 22868026
TI  - Chediak-Higashi syndrome presenting in accelerated phase.
AB  - Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder,
      characterized by silver hair, recurrent infections, partial oculo-cutaneous
      albinism, mild coagulation defect and progressive neuropathy. The characteristic
      feature of CHS is the presence of huge lysosomes and cytoplasmic inclusions
      within different body cells like the white blood cells. The disease has an early
      onset but usually presents in an accelerated phase. We present a case of a 2
      years old boy with high grade fever, bilateral cervical lymphadenopathy,
      hepatosplenomegaly, abdominal distention of 28 days duration. He was diagnosed
      with Chediak-Higashi syndrome in accelerated phase on the basis of clinical
      presentation, morphological findings on peripheral blood film and bone marrow
      aspirate.

PMID- 22868028
TI  - Evaluation of students' performance in elective training in clinical disciplines.

PMID- 22868027
TI  - Inverted papilloma of ureter: a rare cause of hydronephrosis.
AB  - A case of hydronephrosis with a rare underlying cause in a 35 years old male is
      described. He reported with pain in the left lumbar region with a past history of
      left ureterolithotomy. The ultrasound and IVU studies were suggestive of left
      hydronephroureter. CT Scan showed left hydronephroureter with narrowing at the
      lower end of left ureter. Ureterorenoscopy (URS) confirmed polypoidal lesions in
      the left lower ureter, completely obliterating the lumen and involving the whole
      circumferential wall of the lower ureter. The biopsy of the lesion revealed an
      inflammatory polyp. Accordingly open surgical intervention was planned. Excision
      of the lower third of left ureter with ureteric reimplantation was done with a
      Boari flap. The histopathology report of the lower third of ureter confirmed
      inverted papilloma of ureter. The patient made a smooth postoperative recovery.

PMID- 22868029
TI  - Calcifying epithelial odontogenic tumor: case report with immunohistochemical and
      ultrastructural study and review of the literature.

PMID- 22868030
TI  - Synchronous bilateral multifocal acinic cell carcinoma of parotid gland: case
      report and review of the literature.
AB  - A 55-year-old woman presented with a 2-year history of slow growing painless
      masses in both sides of the preauricular area. Ultrasound scanning of the
      bilateral parotid region revealed multiple tumors in both sides of the parotid
      gland. After superficial parotidectomy, selective neck dissection of levels II
      and III were performed on the left side of the parotid gland, and superficial
      parotidectomy was performed on the right side. Histopathologic examination
      revealed both of the sides of parotid gland tumors to be acinic cell carcinoma.
      We discuss the clinicopathologic findings of synchronous bilateral multifocal
      acinic cell carcinoma of the parotid gland.

PMID- 22868031
TI  - Reconstruction of orbital floor defects.

PMID- 22868032
TI  - MatrixMANDIBLE preformed reconstruction plates--a two-year two-institution
      experience in 71 patients.
AB  - PURPOSE: To evaluate handling, complication rates, clinical and treatment
      outcomes of the MatrixMANDIBLE Preformed Reconstruction Plates (MMPRPs), in
      particular with regard to the frequency of fatigue fractures and operative time.
      PATIENTS AND METHODS: A cohort of 71 subjects with an indication for a load
      bearing osteosynthesis of the mandible was enrolled in the present study. The
      indications for plate use were defects due to tumor, trauma, or osteonecrosis.
      The outcome variables were fitting accuracy, application time, and postoperative
      complications, defined as plate exposure, loosening of plates or screws, plate
      fracture, and orocutaneous fistulas. Additionally, the feasibility of a transoral
      approach was tested. RESULTS: The sample included 71 subjects with a mean age of
      54.8 +/- 15.0 years, including 43 men (60.6%). MMPRPs could be placed in 70 of
      the 71 patients. In 10 patients a transoral approach for plate application was
      successfully performed. The mean time investment to contour the plates was 13.1
      minutes. The fitting accuracies of the nonbendable sections were satisfying. No
      plate fracture was observed within an average follow-up period of 11.8 months.
      Postoperative complications occurred in 19 (27.1%) of the 70 patients. Plate
      removal was required in 11 (15.7%) of 70 patients. CONCLUSIONS: The results of
      the present study suggest that the use of MMPRPs coincides with a reduced
      operative time and a minimized risk of fatigue fractures. Thus, MMPRPs seem to be
      a useful standard device in a scope of indications for load-bearing
      osteosynthesis of the anterolateral division of the mandible, additionally
      facilitating a transoral approach for application.

PMID- 22868033
TI  - Intraorbital schwannoma of the abducens nerve: case report.

PMID- 22868034
TI  - Quality of life outcomes after third molar removal in subjects with minor
      symptoms of pericoronitis.
AB  - PURPOSE: Our purpose was to assess the effect of third molar removal on the
      quality of life in subjects with symptoms of pericoronitis. PATIENTS AND METHODS:
      Healthy subjects (American Society of Anesthesiologists Classes I and II), aged
      18 to 35 years, with minor symptoms of pericoronitis affecting at least 1
      mandibular third molar were recruited for an institutional review board-approved
      study. The exclusion criteria were major symptoms of pericoronitis, generalized
      periodontal disease, body mass index greater than 29 kg/m(2), and antibiotic or
      tobacco use. The data from patients undergoing surgery to remove all third molars
      with a follow-up examination after surgery at least 3 months later were included
      in these analyses. The clinical, demographic, and quality of life data were
      collected at enrollment and after surgery. At entry, the debris was removed from
      symptomatic third molar sites; no attempt was made to mechanically remove
      nonsheddable biofilm. The patients scheduled surgery electively with a recall
      examination at least 3 months after surgery. RESULTS: The median age of the 60
      subjects was 21.9 years (interquartile range 20.2 to 24.7). The median
      postoperative follow-up was 7.7 months (interquartile range 6.0 to 12.4). The
      proportion of patients reporting the worst pain as severe decreased from
      enrollment to after surgery from 32% to 3%. Those responding "none" for the worst
      pain increased from 10% to 78%. Fifteen percent of subjects reported the pain
      intensity as "nothing," "faint," or "very weak" at enrollment. This increased to
      96% after surgery. One third of patients reported the unpleasantness of pain as
      "neutral," "slightly unpleasant," or "slightly annoying" at enrollment, which
      increased to 97% after surgery. Also, 22% and 18% of the patients reported "quite
      a bit" or "lots of difficulty" with eating desired foods and chewing foods at
      enrollment, respectively; only 1 patient reported this degree of difficulty at
      the follow-up examination. In contrast, 42% and 37% of the patients reported no
      difficulty with eating and chewing at enrollment, which had increased to 95% and
      93% at the follow-up examination, respectively. CONCLUSIONS: Removal of the third
      molars positively influenced the quality of life outcomes in those with minor
      symptoms of pericoronitis.

PMID- 22868035
TI  - Simultaneous costochondral ramus-condyle reconstruction and mandibular
      distraction for hemifacial microsomia.

PMID- 22868036
TI  - Facial nerve repair with Gore-Tex tube and adipose-derived stem cells: an animal
      study in dogs.
AB  - PURPOSE: Synthetic conduits have been considered a viable option in nerve
      reconstructive procedures. They address the goal of entubulization and eliminate
      the disadvantages of autografts. However, despite all successful reports, none
      has contained regeneration characteristics, such as growth factors or essential
      cells, for nerve repair. The authors evaluated the capability of adipose-derived
      stem cells in Gore-Tex tubes to enhance facial nerve repair. MATERIALS AND
      METHODS: Undifferentiated mesenchymal stem cells were extracted from the
      autogenous adipose tissues of 7 mongrel dogs. The frontal branch of the facial
      nerve was transected. A gap size of 7 mm was repaired with an expanded
      polytetrafluoroethylene tube filled with undifferentiated adipose-derived stem
      cells encapsulated in alginate hydrogel. The control sides were repaired with the
      tube and alginate alone. The healing phase was 12 weeks. RESULTS: Except in 2
      control sides, an organized neural tissue was formed within the tubes. Compared
      with the normal nerve diameter, there was a decreased ratio of 29% and 39% in the
      experimental and control groups, respectively. Neurofilament-positive axon counts
      were 67% of normal values in the 2 groups. There was no significant difference
      between groups in histomorphometric parameters. Nerve conduction velocity in the
      experimental group (28.5 +/- 3.5 m/s) was significantly greater than in the
      control group (16.2 +/- 7 m/s). The experimental group also exhibited a greater
      maximal amplitude of action potential (1.86 +/- 0.24 mV) than the control group
      (1.45 +/- 0.49 mV). CONCLUSIONS: Addition of stem cells in the Gore-Tex tube
      enhanced the neural repair from a functional standpoint. However, for better
      functional and histologic results, differentiated Schwann cells and other
      mediators may be warranted.

PMID- 22868037
TI  - Proteomic analysis on salicylic acid-induced salt tolerance in common wheat
      seedlings (Triticum aestivum L.).
AB  - The influence of salicylic acid (SA) on the salt tolerance mechanism in seedlings
      of common wheat (Triticum aestivum L.) was investigated using physiological
      measurements combined with global expression profiling (proteomics). In the
      present study, 0.5mM SA significantly reduced NaCl-induced growth inhibition in
      wheat seedlings, manifesting as increased fresh weights, dry weights, and
      photosynthetic pigments, but decreased lipid peroxidation. Two-week-old wheat
      seedlings treated with 0.5mM SA, 250 mM NaCl and 250 mM NaCl+0.5mM SA for 3 days
      were used for the proteomic analyses. In total, 39 proteins differentially
      regulated by both salt and SA were revealed by 2D PAGE, and 38 proteins were
      identified by MALDI-TOF/TOF MS. The identified proteins were involved in various
      cellular responses and metabolic processes including signal transduction, stress
      defense, energy, metabolism, photosynthesis, and others of unknown function. All
      protein spots involved in signal transduction and the defense response were
      significantly upregulated by SA under salt stress, suggesting that these proteins
      could play a role in the SA-induced salt resistance in wheat seedlings.

PMID- 22868038
TI  - The morphology of single muscle fibre potentials - Part II: experimental
      findings.
AB  - Studies dealing with single fibre action potentials (SFAPs) have been more
      interested in obtaining quantitative data of certain parameters of the SFAP
      waveform than in the analysis of its morphologic features. The characterization
      of the SFAP morphology is highly valuable as it will allow to obtain information
      about in vivo intracellular action potentials (IAPs). However, the SFAP final
      portion is highly sensitive to distant electrical activity, as shown in Part I of
      this study. The present paper, Part II, is aimed at analysing the morphologies
      found in human SFAPs and deriving data of the associated IAPs. It was found that,
      for most SFAPs (97%), the declining negative phase starts decreasing steeply up
      to a certain point (slope-discontinuity point), from which it returns more slowly
      towards the baseline. This return may be further slowed down due to the
      contamination from distant potentials, but the slope-discontinuity point seems to
      be an intrinsic feature of human SFAPs. The third phase of SFAPs was, either
      absent (65%), or of rather small amplitude and prolonged duration. The slope
      discontinuity point was apparent for the SFAPs of larger amplitude and vanished
      gradually as the SFAPs got smaller. Several lines of evidence strongly suggest
      that the spike duration of human IAPs should be about 1.0 ms.

PMID- 22868039
TI  - Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of
      wakefulness of mice in vivo by blue light.
AB  - Melanopsin (OPN4) is a photosensitive G-protein-coupled photopigment and its
      ectopic expression enables control of neural activity induced by blue light. Here
      we report that we successfully expressed OPN4 in hypothalamic orexin/hypocretin
      neurons of double-transgenic mice (orexin-tTA; Bitet-O human OPN4 [hOPN4]/mCherry
      mice). In the double-transgenic mice, hypothalamic orexin neurons selectively
      expressed hOPN4 as well as mCherry as a reporter. We conducted slice patch-clamp
      recordings on hOPN4/mCherry-expressing orexin neurons, which showed long-lasting
      activation initiated by blue light even after the light was switched off. Optical
      fiber-guided blue light stimulation in the hypothalamus successfully initiated
      the electroencephalography pattern that reflects long-lasting wakefulness in the
      mice in vivo. Taken together, the results indicate that ectopic expression of
      hOPN4 in orexin neurons enables long-lasting activation of orexin neurons by blue
      light to control sleep/wakefulness of the mice.

PMID- 22868040
TI  - Application of a contaminant mass balance method at an old landfill to assess the
      impact on water resources.
AB  - Old and unlined landfill sites pose a risk to groundwater and surface water
      resources. While landfill leachate plumes in sandy aquifers have been studied,
      landfills in clay till settings and their impact on receiving water bodies are
      not well understood. In addition, methods for quantitatively linking soil and
      groundwater contamination to surface water pollution are required. This paper
      presents a method which provides an estimate of the contaminant mass discharge,
      using a combination of a historical investigation and contaminant mass balance
      approach. The method works at the screening level and could be part of a risk
      assessment. The study site was Risby Landfill, an old unlined landfill located in
      a clay till setting on central Zealand, Denmark. The contaminant mass discharge
      was determined for three common leachate indicators: chloride, dissolved organic
      carbon and ammonium. For instance, the mass discharge of chloride from the
      landfill was 9.4 ton/year and the mass discharge of chloride to the deep
      limestone aquifer was 1.4 ton/year. This resulted in elevated concentrations of
      leachate indicators (chloride, dissolved organic carbon and ammonium) in the
      groundwater. The mass discharge of chloride to the small Risby Stream down
      gradient of the landfill was approximately 31 kg/year. The contaminant mass
      balance method worked well for chloride and dissolved organic carbon, but the
      uncertainties were elevated for ammonium due to substantial spatial variability
      in the source composition and attenuation processes in the underlying clay till.

PMID- 22868041
TI  - Characterisation of retroviruses in the horse genome and their transcriptional
      activity via transcriptome sequencing.
AB  - The recently released draft horse genome is incompletely characterised in terms
      of its repetitive element profile. This paper presents characterisation of the
      endogenous retrovirus (ERVs) of the horse genome based on a data-mining strategy
      using murine leukaemia virus proteins as queries. 978 ERV gene sequences were
      identified. Sequences were identified from the gamma, epsilon and betaretrovirus
      genera. At least one full length gammaretroviral locus was identified, though the
      gammaretroviral sequences are very degenerate. Using these data the RNA
      expression of these ERVs were derived from RNA transcriptome data from a variety
      of equine tissues. Unlike the well studied human and murine ERVs there do not
      appear to be particular phylogenetic groups of equine ERVs that are more
      transcriptionally active. Using this novel approach provided a more technically
      feasible method to characterise ERV expression than previous studies.

PMID- 22868042
TI  - New insights into the antigenic structure of the glycoprotein E(rns) of classical
      swine fever virus by epitope mapping.
AB  - The E(rns) glycoprotein of classical swine fever virus (CSFV) has been studied in
      detail concerning biochemical and functional properties, whereas less is known
      about its antigenic structure. In order to define epitopes recognized by CSFV
      specific antibodies, the binding sites of seven E(rns)-specific monoclonal
      antibodies were investigated. Mapping experiments using chimeric E(rns) proteins,
      site-directed mutagenesis and an overlapping peptide library identified one
      antigenic region located between amino acids (aa) 55 to 110 on the E(rns) protein
      of CSFV Alfort/187. The domain comprises three linear motifs *(64)TNYTCCKLQ(72),
      (73)RHEWNKHGW(81), and (88)DPWIQLMNR(96), respectively, and two aa at position
      102 and 107 that are crucial for the interaction with antibodies. Additionally,
      the presentation of the epitope in a correct conformation is mandatory for an
      efficient antibody binding. These findings allow a better understanding of the
      organization and the structure of the E(rns) and provide valuable information
      with regard to the development of E(rns)-based diagnostic tests.

PMID- 22868043
TI  - Laboratory investigations of the effects of nitrification-induced acidification
      on Cr cycling in vadose zone material partially derived from ultramafic rocks.
AB  - Sacramento Valley (California, USA) soils and sediments have high concentrations
      of Cr(III) because they are partially derived from ultramafic material. Some
      Cr(III) is oxidized to more toxic and mobile Cr(VI) by soil Mn oxides. Valley
      soils typically have neutral to alkaline pH at which Cr(III) is highly immobile.
      Much of the valley is under cultivation and is both fertilized and irrigated. A
      series of laboratory incubation experiments were conducted to assess how
      cultivation might impact Cr cycling in shallow vadose zone material from the
      valley. The first experiments employed low (7.1 mmol N per kg soil) and high (35
      mmol Nkg(-1)) concentrations of applied (NH(4))(2)SO(4). Initially, Cr(VI)
      concentrations were up to 45 and 60% greater than controls in low and high
      incubations, respectively. After microbially-mediated oxidation of all NH(4)(+),
      Cr(VI) concentrations dropped below control values. Increased nitrifying
      bacterial populations (estimated by measurement of phospholipid fatty acids) may
      have increased the Cr(VI) reduction capacity of the vadose zone material
      resulting in the observed decreases in Cr(VI). Another series of incubations
      employed vadose zone material from a different location to which low (45 meq kg(
      1)) and high (128 meq kg(-1)) amounts of NH(4)Cl, KCl, and CaCl(2) were applied.
      All treatments, except high concentration KCl, resulted in mean soil Cr(VI)
      concentrations that were greater than the control. High concentrations of water
      leachable Ba(2+) (mean 38 MUmol kg(-1)) in this treatment may have limited Cr(VI)
      solubility. A final set of incubations were amended with low (7.1 mmol Nkg(-1))
      and high (35 mmol Nkg(-1)) concentrations of commercial liquid ammonium
      polyphosphate (APP) fertilizer which contained high concentrations of Cr(III).
      Soil Cr(VI) in the low APP incubations increased to a concentration of 1.8 MUmol
      kg(-1) (5* control) over 109 days suggesting that Cr(III) added with the APP
      fertilizer was more reactive than naturally-occurring soil Cr(III).

PMID- 22868045
TI  - 'There is nothing paranormal about near-death experiences' revisited: comment on
      Mobbs and Watt.

PMID- 22868046
TI  - Survival of bipolar depression, other type of depression and comorbid ailments:
      ten-year longitudinal follow-up of 10,922 Taiwanese patients with depressive
      disorders (KCIS no. PSY1).
AB  - OBJECTIVE: The effect of type of depressive disorder on mortality has been rarely
      addressed in the relevant literature. It is especially true in considering
      comorbid disorders and by population-based longitudinal cohort sample. The aims
      of this study are to compare all-cause and unnatural (suicides and accidents)
      mortality rates between subjects with bipolar depression (BD) and those with
      other types of depression (OTD). METHOD: A cohort of patients diagnosed as
      clinically depressed between 1999 and 2004 according to the National Health
      Insurance Dataset (NHID) were followed until the end of 2008. The occurrence of
      death was identified by the National Mortality Registry (NMR) in Taiwan. Patients
      in this cohort were further classified into BD and OTD groups. Proportional
      hazards regression model were used to evaluate the different mortality risks
      between two groups. RESULTS: BD (n = 1542) was associated with a significantly
      greater risk in all-cause mortality (adjusted hazard ratio = 1.3, 95% CI: 1.1,
      1.5) than was OTD (n = 17,480), even after controlling for demographic features
      and comorbid disorders. BD was associated with approximately twice the risk for
      suicide and accidental death compared with OTD after other variables were held
      constant. Bipolar depression (v.s. OTD) exerted adjusted hazard ratio 3.76 (95%
      CI: 2.17, 6.51) in depressed patients with CVD but only aHR 1.43 (95% CI: 0.79,
      2.58) in those without CVD. CONCLUSIONS: Compared with OTD, BD was related to a
      significantly increased risk for all-cause mortality, suicide, and accidental
      death. Under the comorbidity with CVD, the risk of suicide was 4-fold times more
      likely in BD than in OTD. This magnitude of suicide risk among BD patients
      comorbid with CVD was also higher than those BD without CVD. Thus, patients with
      both BD and CVD may constitute one of groups at highest risk for suicide and
      accidental death.

PMID- 22868047
TI  - The role of loss and danger events in symptom exacerbation in bipolar disorder.
AB  - Research concerned with the association between stressful life events [SLEs] and
      bipolar disorder [BD] is inconsistent. Drawing on the unipolar depression
      literature, specific classifications of events (in particular, humiliation and
      loss events) seem to be especially important, while for anxiety disorders loss
      and danger events have been found to be pertinent. However, little or nothing is
      known about the relationship between such events and BD. The aim of the present
      investigation is to examine the association between danger and loss events and
      symptom exacerbation in BD. A total of 96 BD participants were interviewed using
      the Life Events and Difficulties Schedule [LEDS] at two time points: baseline and
      4 month follow-up. Self-report and observer-rated symptom measures were
      administered at both interviews. The Beck Depression Inventory-Second Edition and
      the Montgomery Asberg Depression Rating Scale were used to measure depressive
      symptoms. The Self-Report Mania Inventory and Clinician-Administered Rating Scale
      for Mania were used to rate manic symptoms. Independent severe events,
      independent loss events and independent danger events were found to be
      significantly associated with worsening of depressive symptoms over an 8-month
      period. No significant associations were observed for manic symptoms. Specific
      relationships with different types of SLEs may explain previous discrepant
      findings concerning the relationship between SLEs and BD.

PMID- 22868048
TI  - Prefrontal cortical thickness in depressed patients with high-risk for suicidal
      behavior.
AB  - Major depressive disorder (MDD) is associated with an increased risk for suicide.
      There is considerable evidence that a predisposition to suicidal behavior may
      exist which is independent of the MDD itself. Recent studies suggest a familial
      transmission of the diathesis for suicidal behavior, reflected in the observation
      of suicide aggregation in families and higher rate of suicidal behavior in first
      degree relatives of suicide attempters with MDD. One of these transmission
      factors may be neurobiological alterations. The main goal of the present study
      was therefore to study abnormalities in cortical thickness in the hypothesized
      fronto-cingulate network in depressed patients with high risk for suicide. 15 MDD
      patients with documented own suicidal behavior and/or with suicidal behavior in
      first-degree relatives (high risk group), 15 depressed patients with non-high
      risk for suicide and 30 matched healthy controls participated in the study. Using
      an automated surface based approach (FreeSurfer) structural T1-weighted volumes
      were analyzed for differences in cortical thickness on a node by node basis
      covering the entire cortex. Patients with high risk for suicide showed
      significantly thinner cortex in the left dorsolateral, ventrolateral prefrontal
      cortex and the anterior cingulate in contrast to non-high risk patients. Together
      with previous morphometric results of our group, this new finding provides strong
      evidence for structural brain alterations in depressed patients with high risk
      for suicide in the fronto-cingulo-striatal network, which is strongly involved in
      reward processing and behavioral/emotional control. This alteration may
      constitute the neurobiological basis for an increased predisposition to suicidal
      behavior.

PMID- 22868049
TI  - Transplanting whole livers from donors less than 6 kilograms--is it prudent?
AB  - INTRODUCTION: Experience suggests transplanting whole liver allografts (WL) from
      donors weighing <6 kg portends a worse prognosis. Patient and allograft survivals
      of infants who underwent transplantation with livers from donors >=6 kg, <6 kg,
      or technical variant allografts from deceased donors (TV) and those from living
      donors (LD) were compared. METHODS: The United Network of Organ Sharing database
      was queried for infant orthotopic liver transplantation (<=2 y). Of 5976
      orthotopic liver transplantations, 860 patients received TV from deceased donors,
      534 received LD split allografts, 509 patients had WL from donors weighing <6 kg,
      and 4073 remaining patients had WL from donors weighing >=6 kg. Kaplan-Meier
      method and log-rank tests were employed. RESULTS: Patients who received WL from
      donors weighing <6 kg had survival mean of 13.9 y +/- 177 d. Overall patient
      survivals were 76.7%, 71.4%, 68.4%, and 65.9% at 1, 3, 5, and 10 y. This is
      significantly worse compared with all other groups, both in patient and allograft
      survival (P <= 0.001). In patients whose donors >=6 kg, overall patient survivals
      were 82.1%, 78.7%, 77.3%, and 75.4% at 1, 3, 5, and 10 y. Infants who received TV
      had patient survival of 87.8%, 84.7%, 82.7%, and 80.6% at 1, 3, 5, and 10 y.
      Infants who received LD allografts had patient survival of 92.4%, 90.7%, 89.6%,
      and 88.5% at 1, 3, 5, and 10 y. CONCLUSIONS: Smaller weight of the donor
      influences the infant patient outcome. Patients with allografts from donors
      weighing <6 kg have a worse prognosis compared with those who received TV and LD
      allografts and those whose donors weigh >=6 kg. Patients who receive LD
      allografts had the best survival.

PMID- 22868050
TI  - Remote ischemic perconditioning--a simple, low-risk method to decrease ischemic
      reperfusion injury: models, protocols and mechanistic background. A review.
AB  - Interruption of blood flow can cause ischemic reperfusion injury, which sometimes
      has a fatal outcome. Recognition of the phenomenon known as reperfusion injury
      has led to initial interventional approaches to lessen the degree of damage. A
      number of efficient pharmacologic agents and surgical techniques (e.g., local
      ischemic preconditioning and postconditioning) are available. A novel,
      alternative approach to target organ protection is remote ischemic conditioning
      triggered by brief repetitive ischemia and reperfusion periods in distant organs.
      Among the different surgical techniques is so-called remote ischemic
      perconditioning, a method that applies short periods of ischemic reperfusion to a
      distant organ delivered during target organ ischemia. Although ischemic
      reperfusion injury is reduced by this technique, the explanation for this
      phenomenon is still unclear, and approximately only a dozen reports on the topic
      have appeared in the literature. In our study, therefore, we investigated the
      connective mechanisms, signal transduction, and effector mechanisms behind remote
      perconditioning, with a review on molecular background and favorable effects. In
      addition, we summarize the various treatment protocols and models to promote
      future experimental and clinical research.

PMID- 22868052
TI  - A relationship between mechanically-induced changes in serum cartilage oligomeric
      matrix protein (COMP) and changes in cartilage thickness after 5 years.
AB  - OBJECTIVE: To evaluate the hypothesis that a mechanical stimulus (30-min walk)
      will produce a change in serum concentrations of cartilage oligomeric matrix
      protein (COMP) that is associated with cartilage thickness changes on magnetic
      resonance imaging (MRI). METHODS: Serum COMP concentrations were measured by
      enzyme-linked immunosorbent assay in 17 patients (11 females, age: 59.0+/-9.2
      years) with medial compartment knee osteoarthritis (OA) at study entry
      immediately before, immediately after, 3.5 h, and 5.5 h after a 30-min walking
      activity. Cartilage thickness changes in the medial femur and medial tibia were
      determined from MR images taken at study entry and at 5-year follow-up.
      Relationships between changes in cartilage thickness and COMP levels, with post
      activity concentrations expressed as a percentage of pre-activity levels, were
      assessed by the calculation of Pearson correlation coefficients and by multiple
      linear regression analysis, with adjustments for age, sex, and body mass index
      (BMI). RESULTS: Changes in COMP levels 3.5 h and 5.5 h post-activity were
      correlated with changes in cartilage thickness in the medial femur and tibia at
      the 5-year follow-up. The results were strengthened after analyses were adjusted
      for age, sex, and BMI. Neither baseline pre-activity COMP levels nor changes in
      COMP levels immediately post-activity were correlated with cartilage thickness
      changes. CONCLUSIONS: The results of this study support the hypothesis that a
      change in COMP concentration induced by a mechanical stimulus is associated with
      cartilage thinning at 5 years. Mechanically-induced changes in mechano-sensitive
      biomarkers should be further explored in the context of stimulus-response models
      to improve the ability to assess OA progression.

PMID- 22868051
TI  - Histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates Toll
      like receptor 4 signaling in lipopolysaccharide-stimulated mouse macrophages.
AB  - OBJECTIVE: We have previously demonstrated that pretreatment and posttreatment of
      animals with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase
      inhibitor, can improve survival in a mouse model of lipopolysaccharide (LPS)
      induced severe shock. This study was designed to assess whether SAHA affects
      LPS/Toll-like receptor 4 signaling through acetylation of heat shock protein 90
      (HSP90) and degradation of its client protein interleukin-1 receptor-associated
      kinase 1 (IRAK1). METHODS: RAW264.7 cells were exposed to LPS (1 MUg/mL) for 2 h,
      followed by treatment with SAHA (10 MUM) or geldanamycin (3 MUM), an inhibitor of
      HSP90. Sham (no SAHA, no LPS) macrophages served as a control. The cells were
      harvested at different time points, and time zero served as the reference point.
      RESULTS: LPS dramatically increased protein expression of myeloid differentiation
      factor 88 and IRAK1, and stimulated nuclear translocation of nuclear factor
      kappaB, leading to an increases of gene expression and protein production of
      tumor necrosis factor alpha and interleukin-6. Treatment with SAHA significantly
      attenuated these LPS-stimulated alterations. LPS or SAHA did not change the
      levels of HSP90 protein, but immunoprecipitation studies demonstrated that SAHA
      treatment enhanced acetylation of HSP90, and increased the dissociation of IRAK1,
      compared to the LPS control. CONCLUSIONS: SAHA suppresses LPS/Toll-like receptor
      4 signaling in LPS-stimulated macrophages through multiple potential mechanisms.
      It inhibits the function of HSP90 through hyperacetylation of the chaperone
      protein, which results in dissociation and degradation of the client protein
      IRAK1 and, at least in part, leads to a decrease in nuclear translocation of
      nuclear factor kappaB and attenuation of key proinflammatory cytokine expression.

PMID- 22868053
TI  - Quantitative analysis (K(d) and IC(50)) of glycoconjugates interactions with a
      bacterial lectin on a carbohydrate microarray with DNA Direct Immobilization
      (DDI).
AB  - Nowadays, there is a great interest for understanding the structure/function
      relationship governing recognition of carbohydrates by their receptors for the
      design of new treatments. Indeed, carbohydrates and glycoconjugates play a major
      role in key biological events such as cell-cell recognition, pathogenesis
      inflammation, and host pathogen interactions. Pseudomonas aeruginosa (PA) is one
      of the predominant bacterium encountered in nosocomial infections. PA infections
      often lead to chronic inflammation and eventually to death despite aggressive
      antibiotic therapy: the emergence of resistant strains and biofilm formation
      seems to give a selective advantage to the bacterium. A promising approach is to
      inhibit the virulence factors of PA such as PA-IL which is a galactose specific
      lectin. Herein, we develop a microarray to probe the binding of six galacto
      conjugates to PA-IL differing by their spatial configuration and geometry. This
      microsystem is made of 40 independent microwells in which 64 spots of
      glycoconjugates probes are arrayed by using DNA Directed Immobilization (DDI).
      This microsystem allows, in a multiplex fashion, qualitative information on the
      binding by direct fluorescence readout as well as quantitative information by the
      determination of IC(50) values in a competition assay and surface dissociation
      constants (K(d)). According to our data, direct fluorescent signals (FI(635)),
      IC(50) and K(d) values provided similar ranking for glycoconjugates with respect
      to PA-IL binding thus affording a general tool for the selection of galacto
      conjugates displaying the best affinities toward PA-IL.

PMID- 22868054
TI  - Highly sensitive near-simultaneous assay of multiple "lean meat agent" residues
      in swine urine using a disposable electrochemiluminescent immunosensors array.
AB  - Nowadays, beta(2)-agonists are abused illegally as "lean meat agents" for food
      producing animals, and cause increasing food-safety accidents in some countries.
      Due to their hazard to the human health, "lean meat agents" are banned in most
      countries and required to be routinely monitored. We herein report a disposable
      electrochemiluminescent immunosensors array for near-simultaneous assay of
      multiple beta(2)-agonist residues in swine urine, by using ractopamine and
      salbutamol as the models. In this investigation, a screen-printed carbon
      electrodes array was assembled and acted as the substrate of the immunosensors
      array. Then the immunosensors array was constructed by site-selectively
      immobilizing the antigens of ractopamine and salbutamol on the working electrodes
      of array. After the competitive immuno-binding, with the aid of a homemade single
      pore-four-throw switch, the electrochemiluminescent signals of the two beta(2)
      agonists were sequentially detected using a non-array detector. The limits of
      detection for ractopamine and salbutamol were 8.5 and 17pg/mL, respectively,
      which were much lower than those of the most previous reports. Compared with
      other routine methods based on chromatography and ELISA, this method is more
      suitable for screening of multiple beta(2)-agonists in quantities of samples,
      owing to its merits of low cost, user-friendliness and high throughput, and shows
      great promise in food safety and agonist surveillance.

PMID- 22868055
TI  - Biosensor based on acetylcholinesterase immobilized onto layered double
      hydroxides for flow injection/amperometric detection of organophosphate
      pesticides.
AB  - We developed a highly sensitive flow injection/amperometric biosensor for the
      detection of organophosphate pesticides (OPs) using layered double hydroxides
      (LDHs) as the immobilization matrix of acetylcholinesterase (AChE). LDHs provided
      a biocompatible microenvironment to keep the bioactivity of AChE, due to the
      intrinsic properties of LDHs (such as a regular structure, good mechanical,
      chemical and thermal stabilities, and swelling properties). By integrating the
      flow injection analysis (FIA) with amperometric detection, the resulting AChE
      LDHs modified electrode greatly catalyzed the oxidation of the enzymatically
      generated thiocholine product, and facilitated the detection automation, thus
      increasing the detection sensitivity. The analytical conditions for the
      FIA/amperometric detection of OPs were optimized by using methyl parathion (MP)
      as a model. The inhibition of MP was proportional to its concentration ranging
      from 0.005 to 0.3MUg mL(-1) and 0.3 to 4.0MUg mL(-1) with a detection limit 0.6ng
      mL(-1) (S/N=3). The developed biosensor exhibited good reproducibility and
      acceptable stability.

PMID- 22868056
TI  - Activity monitoring in patients with depression: a systematic review.
AB  - BACKGROUND: Altered physical activity is an important feature of depression. It
      is manifested in psychomotor retardation, agitation and withdrawal from
      engagement in normal activities. Modern devices for activity monitoring
      (actigraphs) make it possible to monitor physical activity unobtrusively but the
      validity of actigraphy as an indicator of mood state is uncertain. We carried out
      a systematic review of digital actigraphy in patients with depression to
      investigate the associations between measured physical activity and depression.
      METHODS: Systematic review and meta-analysis. Studies were identified from
      Medline, EMBASE and Psycinfo databases and included if they were either case
      control or longitudinal studies of actigraphy in adults aged between 18 and 65
      diagnosed with a depressive disorder. Outcomes were daytime and night-time
      activity and actigraphic measures of sleep. RESULTS: We identified 19 eligible
      papers from 16 studies (412 patients). Case control studies showed less daytime
      activity in patients with depression (standardised mean difference -0.76, 95%
      confidence intervals -1.05 to -0.47). Longitudinal studies showed moderate
      increase in daytime activity (0.53, 0.20 to 0.87) and a reduction in night-time
      activity (-0.36, -0.65 to -0.06) over the course of treatment. LIMITATIONS: All
      study participants were unblinded. Only seven papers included patients treated in
      the community. CONCLUSIONS: Actigraphy is a potentially valuable source of
      additional information about patients with depression. However, there are no
      clear guidelines for use of actigraphy in studies of patients with depression.
      Further studies should investigate patients treated in the community. Additional
      work to develop algorithms for differentiating behaviour patterns is also needed.

PMID- 22868057
TI  - Attention deficit hyperactivity disorder characteristics: II. Clinical correlates
      of irritable mood.
AB  - BACKGROUND: This study describes the relationship of irritable mood (IRR) with
      affective disorders in youths with attention deficit hyperactivity disorder
      (ADHD). METHODS: Five hundred ADHD subjects were assessed with the childhood
      version of the Schedule for Affective Disorder & Schizophrenia. Subjects were in
      a genetic ADHD protocol and limited to those of Caucasian/European descent.
      RESULTS: The most prevalent concurrent diagnoses were oppositional defiant
      disorder (ODD) (43.6%), minor depression/dysthymic disorder (MDDD) (18.8%), and
      generalized anxiety (13.2%)/overanxious disorder (12.4%). IRR subjects (21.0%)
      compared to the non-IRR (NIRR) group had higher rates of all affective disorders
      (76.2% vs. 9.6%) and ODD (83.8% vs. 32.9%) but lower rates of hyperactive ADHD
      (1.9% vs. 8.9%). Among those without comorbidities, 98.3% were NIRR. Logistic
      regression found IRR mood significantly associated with major depressive disorder
      (odds ratio [OR]: 33.4), MDDD (OR: 11.2), ODD (OR: 11.6), and combined ADHD (OR:
      1.7) but not with anxiety disorders. Among symptoms, it associated IRR mood with
      a pattern of dysthymic and ODD symptoms but with fewer separation anxiety
      symptoms. Diagnostic and symptomatic parameters were unaffected by demographic
      variables. LIMITATIONS: Potential confounders influencing these results include
      patient recruitment from only one clinical service; a cohort specific sample
      effect because some presumed affective disorders and non-Caucasians were
      excluded; and the young mean age (10.2 years) limiting comorbid patterns.
      CONCLUSIONS: The prominence of an MDDD pattern suggests this IRR group is
      appropriate in the DSM V's proposed chronic depressive disorder, possibly with or
      without temper dysregulation. A new diagnosis of disruptive mood dysregulation
      disorder may be unwarranted.

PMID- 22868058
TI  - Discriminating melancholic and non-melancholic depression by prototypic clinical
      features.
AB  - BACKGROUND: Melancholia is positioned as either a more severe expression of
      clinical depression or as a separate entity. Support for the latter view emerges
      from differential causal factors and treatment responsiveness but has not been
      convincingly demonstrated in terms of differential clinical features. We pursue
      its prototypic clinical pattern to determine if this advances its delineation.
      METHODS: We developed a 24-item measure (now termed the Sydney Melancholia
      Prototype Index or SMPI) comprising 12 melancholic and 12 non-melancholic
      prototypic features (both symptoms and illness correlates). In this evaluative
      study, 278 patients referred for tertiary level assessment at a specialized mood
      disorders clinic completed the self-report SMPI as well as a depression severity
      measure and a comprehensive assessment schedule before clinical interview, while
      assessing clinicians completed a clinician version of the SMPI items following
      their interview. The independent variable (diagnostic gold standard) was the
      clinician's judgment of a melancholic versus non-melancholic depressive episode.
      Discriminative performance was evaluated by Receiver Operating Characteristics
      (ROC) analysis of four strategies for operationalising the SMPI self-report and
      SMPI clinician measures, and with the former strategies compared to ROC analysis
      of the depression severity measure. The external validity of the optimally
      discriminating scores on each measure was tested against a range of clinical
      variables. RESULT: Comparison of the two self-report measures established that
      the SMPI provided greater discrimination than the depression severity measure,
      while comparison of the self-report and clinician-rated SMPI measures established
      the latter as more discriminating of clinically diagnosed melancholic or non
      melancholic depression. ROC analyses favoured self-report SMPI distinction of
      melancholic from non-melancholic depression being most optimally calculated by a
      'difference' score of at least four or more melancholic than non-melancholic
      items being affirmed (sensitivity of 0.69, specificity of 0.77). For the
      clinician-rated SMPI measure, ROC analyses confirmed the same optimal difference
      score of four or more as highly discriminating of melancholic and non-melancholic
      depression (sensitivity of 0.84, specificity of 0.92). As the difference score
      had positive predictive values of 0.90 and 0.70 (for the respective clinician
      rated and self-report SMPI forms) and respective negative predictive values of
      0.88 and 0.70, we conclude that the clinician-rated version had superior
      discrimination than the self-report version. External validating data quantified
      the self-rated and clinician-rated Index-assigned non-melancholic patients having
      a higher prevalence of anxiety disorders, a higher number of current and lifetime
      stressors, as well as elevated scores on several personality styles that are
      viewed as predisposing to and shaping such non-melancholic disorders.
      LIMITATIONS: Assigned melancholic and non-melancholic diagnoses were determined
      by clinician judgement, risking a circularity bias across diagnostic assignment
      and clinical weighting of melancholic and non-melancholic features. The
      robustness of the Index requires testing in primary and secondary levels of care
      settings. CONCLUSIONS: The clinician-rated SMPI differentiated melancholic and
      non-melancholic depressed subjects at a higher level of confidence than the self
      report SMPI, and with a highly acceptable level of discrimination. The measure is
      recommended for further testing of its intrinsic and applied properties.

PMID- 22868059
TI  - Effect of asenapine on manic and depressive symptoms in bipolar I patients with
      mixed episodes: results from post hoc analyses.
AB  - BACKGROUND: The efficacy of agents useful for mania is largely unproven in
      patients with mixed episodes. METHODS: The efficacy of asenapine in the treatment
      of mixed episodes was assessed using post hoc analyses on pooled data from two
      identically designed 3-week, randomized, double-blind, flexible dose, placebo-
      and olanzapine-controlled trials and their 9-week, double-blind olanzapine
      controlled extension study. Efficacy was measured by changes on Young Mania
      Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) total
      scores, and was analysed through analysis of covariance on observed cases of the
      intent-to-treat dataset. RESULTS: In the intent-to-treat population, 295 patients
      had a DSM-IV-TR mixed episode (placebo: 66; olanzapine: 122; asenapine: 107) in
      the 3-week trials. Of these, 102 patients (olanzapine: 56; asenapine: 46) entered
      the 9-week extension study. At week 3, decreases in YMRS and MADRS total scores,
      were significantly (p<0.01) greater with asenapine (YMRS: -15.0; MADRS: -8.2)
      versus placebo (YMRS: -11.5; MADRS: -4.5); olanzapine did not separate from
      placebo (YMRS: -13.3; MADRS: -6.5). At week 12, further decreases in YMRS and
      MADRS total scores were observed with asenapine (YMRS: -22.4; MADRS: -11.9); non
      statistically different from olanzapine (YMRS: -20.2; MADRS: -7.9). LIMITATIONS:
      Results are from post hoc analyses of trials that were not designed to
      specifically evaluate mixed episodes. CONCLUSIONS: These exploratory analyses
      provide supportive evidence for the efficacy of asenapine in treating the
      associated symptoms of mania and depression in bipolar I patients with mixed
      episodes.

PMID- 22868060
TI  - Angiotensin-(1-7) central administration induces anxiolytic-like effects in
      elevated plus maze and decreased oxidative stress in the amygdala.
AB  - There is increasing evidence that besides the well-known angiotensin (Ang) II,
      other renin-angiotensin system (RAS) peptides, including Ang-(1-7), could have
      important effects at the central level. However, very few things are known about
      the central actions of Ang-(1-7), while the effects of its administration alone
      on anxiety have not been tested to date, to the best of our knowledge. In this
      way, we were interested in studying the effects of Ang-(1-7)
      intracerebroventricular administration on anxiety levels, as studied through some
      main behavioral parameters in the elevated plus maze, as well as the importance
      of Ang-(1-7) in the oxidative stress status from the amygdala, which is one of
      the key brain regions involved in mediating anxiety. We report here a possible
      anxiolytic-like effect of Ang-(1-7) administration, as demonstrated by the
      increased percentage of time spent and frequency of entries in the open arms of
      the elevated plus maze, as well as increased head-dipping behavior in the open
      arms and decreased stretching in closed arms. Also some antioxidant effects of
      Ang-(1-7) are suggested since a significant increase of GPX specific activity and
      a decrease of the main peroxidation marker MDA were observed in the amygdala.
      Moreover, we found a significant correlation between most of the behavioral
      parameters in the elevated plus maze and the levels of the oxidative stress
      markers. However, further studies are necessary in order to elucidate the effects
      of Ang-(1-7) administration on anxiety and oxidative stress status and also on
      the possible correlation that might exists between these aspects.

PMID- 22868061
TI  - The role of serotonergic genes and environmental stress on the development of
      depressive symptoms and neuroticism.
AB  - BACKGROUND: Depression is considered to be the result of a complicated synergy
      between genetic and environmental factors. Several genes of the serotonergic
      neurotransmission have been related to depression phenotypes, however results are
      inconsistent, possibly due to the oversight of the role of environmental stress.
      METHODS: We examined gene-environment (GxE) interactions with serotonergic genes
      on depressive symptoms and neuroticism in a homogeneous population-based sample
      of 415 females. We chose several genetic variants within candidate genes (SLC6A4,
      TPH2, HTR1A) that have been previously found to provide some evidence of
      association with depression outcomes. RESULTS: Single marker analyses showed a
      significant GxE interaction with several TPH2 variants, including rs4570625, on
      depressive symptoms. Significant GxE interactions were also observed with TPH2
      haplotypes. No reliable associations were observed with SLC6A4 and HTR1A genes.
      We did not find any robust evidence of a direct impact of serotonergic genes on
      depressive symptoms or neuroticism. LIMITATIONS: Due to the high number of
      analyses conducted, results must be interpreted with caution. CONCLUSIONS: The
      present study indicates an association between TPH2 and depressive symptoms that
      is conditional on prior experience of stressful life events. Further evidence is
      provided about the role of the environment in genetic vulnerability to
      depression.

PMID- 22868062
TI  - Psychometric properties of the Slovenian version of temperament evaluation of
      Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A): temperament
      profiles in Slovenian university students.
AB  - BACKGROUND: TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego
      Autoquestionnaire) is a self-rated instrument that measures five affective
      temperaments: depressive, cyclothymic, hyperthymic, irritable, and anxious. The
      aim of our study was to examine the psychometric characteristics of the Slovenian
      TEMPS-A and to ascertain if temperament profile is related to the professions
      chosen by Slovenian students. METHODS: 892 Slovenian university students in six
      different professional fields (economics, geography, engineering, law, sports
      pedagogy and nursing) were included in our study. RESULTS: Cronbach's reliability
      coefficients denoted acceptable internal consistency of the subscales. Principal
      component analysis revealed relatively good internal structure of the instrument.
      Nursing and geography students scored the highest on depressive temperament.
      Sports pedagogues as well as engineers demonstrated the most firm personality
      structure with distinctive hyperthymic temperament. Law students revealed the
      most irritable temperament, while nursing and law students scored the highest on
      anxious temperament. LIMITATIONS: Sample of Slovenian students is not
      representative for general population. The structure of the sample was crucial as
      well, as it comprised mainly of younger students who just started their study.
      CONCLUSIONS: The Slovenian version of the TEMPS-A proved to have relatively good
      internal consistency and internal structure. The questionnaire verified as a
      reliable and valid instrument and generally in line with previous studies. This
      study strengthens the perspective that professional areas could be associated
      with distinct affective temperament profile that could influence career
      decisions. The findings in students of economics, geography, and sport pedagogy
      are new as they have not been previously investigated by TEMPS researchers. The
      results open new possibilities for future research.

PMID- 22868064
TI  - The role of granulocyte and monocyte apheresis in inflammatory bowel disease.

PMID- 22868063
TI  - Elevated gray matter volume of the emotional cerebellum in women with
      premenstrual dysphoric disorder.
AB  - OBJECTIVE: Premenstrual dysphoric disorder (PMDD) is characterized by severe,
      negative mood symptoms during the luteal phase of each menstrual cycle. We
      recently reported that women with PMDD show a greater increase in relative
      glucose metabolism in the posterior cerebellum from the follicular to the luteal
      phase, as compared with healthy women, and that the phase-related increase is
      proportional to PMDD symptom severity. We extended this work with a study of
      brain structure in PMDD. METHODS: High-resolution magnetic resonance imaging
      (MRI) scans were obtained from 12 women with PMDD and 13 healthy control subjects
      (whole-brain volume-corrected p<.05). Voxel-based morphometry was used to assess
      group differences in cerebral grey-matter volume (GMV), using a statistical
      criterion of p<.05, correcting for multiple comparisons in the whole-brain
      volume. RESULTS: PMDD subjects had greater GMV than controls in the posterior
      cerebellum but not in any other brain area. Age was negatively correlated with
      GMV within this region in healthy women, but not in women with PMDD. The group
      difference in GMV was significant for women over age 30(p=.0002) but not younger
      participants (p>.1). CONCLUSIONS: PMDD appears to be associated with reduced age
      related loss in posterior cerebellar GMV. Although the mechanism underlying this
      finding is unclear, cumulative effects of symptom-related cerebellar activity may
      be involved.

PMID- 22868065
TI  - Bell's palsy in a patient receiving adalimumab for Crohn's disease.

PMID- 22868066
TI  - [Mastectomy and immediate breast reconstruction using a prosthesis and lower
      dermal flap: description of five cases].
AB  - INTRODUCTION: When performing mastectomy involving immediate reconstruction with
      prosthesis, it is required to obtain a complete cover of the implant. However,
      this is hardly ever possible for patients having a significant breast volume,
      despite the use of the skin-reducing technique. Using the lower dermal flap makes
      it possible to fully cover the implant for these patients. PATIENTS AND METHODS:
      We will describe five cases of patients on whom skin-reducing mastectomy and
      immediate reconstruction with prosthesis and lower dermal flap were performed.
      Preoperative drawings were made following the so-called "Saint-Louis" pattern.
      During surgery, the future skin flap representing the skin cover of lower breast
      quadrants was de-epidermised. Mastectomy was then performed via an incision at
      the upper limit of the future flap. Then, a retro-pectoral pocket was created by
      lifting the pectoralis major muscle. The implant was introduced into this pocket
      and covered up at its lower part by the dermal flap, the upper edge of which was
      sutured to the lower edge of the pectoralis major muscle. The implant was thereby
      fully covered. Finally, the skin was closed with inverted T-scars. RESULTS:
      Postoperative effects were minor. Two patients suffered from skin pain at the
      junction between the vertical and horizontal scars of the inverted T. These
      injuries were treated via healing by secondary intention. We have not observed
      any infection. Cosmetic results assessed by the patients and surgical team were
      considered as satisfactory. CONCLUSION: Mastectomy with immediate reconstruction
      using a prosthesis and lower dermal flap makes it possible to fully cover the
      implant in patients who require the skin-reducing technique. This technique seems
      to minimise the risk of major complications and generates satisfactory cosmetic
      results.

PMID- 22868067
TI  - No effects of monosodium glutamate consumption on the body weight or composition
      of adult rats and mice.
AB  - Monosodium glutamate (MSG) is pervasively consumed as a flavor enhancer so there
      are important implications to understanding its physiological actions,
      particularly its effects on body weight. Previous studies suggest that MSG
      increases, decreases, or has no effect on the body weight of rodents. However,
      most of these studies involved administration of MSG to immature rodents and
      consequently may not be relevant for understanding human obesity. We report here
      five experiments in which we measured the body weights of a total of 32 groups of
      10-12 adult rats or mice given various diets to eat and MSG to eat or drink. We
      found no evidence that MSG influenced body weight, energy intake, or body
      composition. To the extent that experiments in rodents illuminate mechanisms
      involved in human obesity and body weight control, our results suggest that MSG
      is unlikely to be a useful anti-obesity supplement but neither is it responsible
      for exacerbating obesity.

PMID- 22868068
TI  - Breast milk metal ion levels in a young and active patient with a metal-on-metal
      hip prosthesis.
AB  - Metal-on-metal resurfacing arthroplasty of the hip has been used increasingly
      over the last 10 years in younger active patients. The dissolution of the metal
      wear particles results in measurable increases in cobalt and chromium ions in the
      serum and urine of patients with a metal-on-metal bearing. We measured the
      cobalt, chromium, and molybdenum ion levels in urine; serum; and breast milk in a
      young and active patient with a metal-on-metal hip prosthesis after a pathologic
      fracture of the femoral neck. Metal-on-metal hip prosthesis leads to increasing
      levels of molybdenum in breast milk in the short-term follow-up. There are no
      increasing levels of chromium and cobalt ions in breast milk. Besides the already
      known elevated concentrations in serum of chromium and cobalt after implantation
      of a metal-on-metal hip prosthesis, we found no increasing levels of chromium and
      cobalt in urine.

PMID- 22868069
TI  - Cementless total hip arthroplasty with modified oblique femoral shortening
      osteotomy in Crowe type IV congenital hip dislocation.
AB  - Midterm results of cementless total hip arthroplasty in patients with Crowe type
      IV congenital dislocation of the hip were evaluated. A modified oblique
      subtrochanteric shortening osteotomy was used in all patients. A cylindrical
      femoral stem was used in all patients to stabilize the osteotomy. Mean follow-up
      was 82 months in 20 hips of 16 patients. Mean Merle D'Aubigne pain score
      increased from 2.52 to 5.65 points, function score improved from 4.0 to 5.3
      points, and mobility score improved from 3.95 to 5.35. Mean greater trochanter
      height relative to the estimated hip center was 6.8 +/- 2.0 cm preoperatively and
      -1 +/- 0.2 cm postoperatively. Complications were dislocations in 3 patients,
      which were successfully managed without redislocation and fracture of greater
      trochanter in 3 patients, which healed uneventfully in 2 but with residual
      Trendelenburg gait in one. Total hip arthroplasty with modified oblique
      subtrochanteric shortening osteotomy is an effective technique for the treatment
      for Crowe type IV hip dislocation.

PMID- 22868071
TI  - Epidemiology of primary hip and knee arthroplasties in Germany: 2004 to 2008.
AB  - The objective of this study was to describe the trend in utilization of primary
      joint arthroplasties in Germany. Between 2004 and 2008, the number of total knee
      arthroplasties (TKAs) increased faster than that of total hip arthroplasties
      (THAs). In 2008, 159000 primary THAs and 146000 primary TKAs were performed. This
      represented a 15% increase in THAs and a 33% increase in TKAs compared to 2004.
      The annual increase in number of surgeries was 4500 for THAs and 9,000 for TKAs.
      Although older adults remained the main recipients of joint arthroplasties,
      incidence rate increased faster in non-elderly(18-64 years) compared with elderly
      (>=65 years) in both THAs and TKAs. Obesity, more strongly associated with TKAs
      than with THAs, could be a contributor to the recent steeper growth in TKAs in
      Germany.

PMID- 22868070
TI  - Leukocyte esterase from synovial fluid aspirate: a technical note.
AB  - Accurate and efficient diagnosis of periprosthetic joint infection remains one of
      the most challenging tasks for orthopedic surgeons. Currently, no widely used
      diagnostic test allows for quick and efficient performance, low cost, and high
      sensitivity and specificity. Aspiration of synovial fluid from a patient's joint
      can be done in the clinic both quickly and easily; oftentimes, the aspirate
      obtained is bloody, thus rendering the use of colorimetric strip testing
      impractical. We describe a simple, inexpensive, and effective protocol using
      centrifugation to allow for leukocyte esterase (LE) testing after bloody joint
      aspirations. In all cases, both septic and aseptic, there was a 100% concordance
      in LE enzyme test results. Although further validation may be necessary, these
      initial results demonstrate that accuracy of LE testing is not affected by
      centrifugation.

PMID- 22868072
TI  - Disparity in total joint arthroplasty patient comorbidities, demographics, and
      postoperative outcomes based on insurance payer type.
AB  - Little is known about how patient characteristics differ between insurance types.
      We reviewed 293 consecutive primary total joint arthroplasty patients with 12
      month follow-up and stratified them based on insurance type. As compared with
      patients with either Medicare or private insurance, Medicaid patients traveled an
      extra 160 to 170 miles for access to care, both Iowa Care and Medicaid were more
      than 3 times more likely to be current smokers, and both Iowa Care and Medicaid
      had lower preoperative and 12-month postoperative 36-Item Short Form Health
      Survey and WOMAC outcomes scores. Payer type was a significant predictor of 36
      Item Short Form Health Survey physical function at final follow-up in a
      multivariate analysis. Significant disparities exist between patients with
      different insurance payer types in total joint arthroplasty, and further research
      into these differences is necessary.

PMID- 22868073
TI  - Coronal alignment correlates with outcome after total knee arthroplasty: five
      year follow-up of a randomized controlled trial.
AB  - In a prospective randomized control trial comparing computer-assisted vs
      conventional total knee arthroplasty, we previously reported that patients with
      coronal alignment within 3 degrees  of neutral had superior international knee
      society and Short-Form 12 (SF-12) physical scores at 6 weeks, 3 months, 6 months,
      and 12 months after surgery. Computer-assisted total knee arthroplasty achieved
      greater accuracy in implant alignment, and this correlated with better knee
      function and quality of life. At 5 years, 90 of 111 patients assessed in our
      original study were reviewed. Coronal alignment within 3 degrees  of neutral
      continued to be correlated with superior International Knee Society and SF-12
      scores. Coronal alignment greater than 3 degrees  was associated with a
      significant decline in SF-12 mental health scores.

PMID- 22868074
TI  - Incidence of osteolysis in total knee arthroplasty: comparison between
      radiographic and retrieval analysis.
AB  - Detection of polyethylene wear and osteolysis in total knee arthroplasty using
      radiographs is imprecise. To correlate radiographic findings with retrieved
      tibial component analysis, we reviewed knee revision cases. A joint registry was
      used to identify all knee revisions. Radiographic scoring systems were developed.
      Radiographs were analyzed for osteolysis and implant alignment. Polyethylene
      liner retrievals were visually and optically graded for surface damage.
      Statistical analyses that included correlation analysis and Mann-Whitney U test
      were used. When osteolysis was found, radiographic scores and delamination score
      were significantly higher (P = .047 and P = .014, respectively). Delamination is
      a good indicator for polyethylene wear and osteolysis. There is a need to develop
      in vivo methods to identify polyethylene changes and thereby prevent severe
      clinical outcomes.

PMID- 22868075
TI  - Operative treatment of early peri-prosthetic femur fractures following primary
      total hip arthroplasty.
AB  - The risk factors for and results of operatively treated peri-prosthetic femoral
      fractures sustained within 90 days following primary THA were evaluated. 5,313
      consecutive THAs were reviewed and 32 (0.60%) fractures were identified which
      included 9 A(g), 2 B(1), 18 B(2), 1 B(3), and 2 A(g)/B(2) fractures. 19 (61%)
      patients sustained 23 complications including 9 greater trochanter non-unions, 2
      femoral shaft non-unions, 3 patients with Brooker III HO, and 2 deep infections.
      7 patients (23%) required a second operative procedure and one patient required a
      third. Peri-prosthetic fractures were associated with advancing age, female
      gender, developmental hip dysplasia, and cementless metaphyseal engaging
      components, particularly flat wedge tapers. Overall, operative treatment of acute
      peri-prosthetic fractures is associated with a high rate of complications (61%)
      and re-operation (23%).

PMID- 22868076
TI  - Henry's pelvic deltoid: antiquated concept or important consideration for total
      hip arthroplasty? An anatomical study.
AB  - The relevance of Henry's pelvic deltoid and its contribution to hip abductor
      strength is often not considered in hip arthroplasty. This small cadaveric study
      (n = 11) aimed to quantify the relative contributions of the pelvic deltoid
      muscles to abductor strength and to assess how different surgical
      approaches(anterolateral, direct lateral and posterior) impact on each of these
      muscle groups. We inspected the path of each approach and measured the cross
      sectional area of the hip abductors, from which the contribution of each muscle
      to abductor moment was derived. We concluded that the posterior approach has the
      least impact on the pelvic deltoid and overall abductor moment.

PMID- 22868077
TI  - Creation of a femoral cortical window to facilitate total hip arthroplasty in
      patients with sickle cell hemoglobinopathies.
AB  - Patients with sickle cell hemoglobinopathies often have femoral head
      osteonecrosis with collapse, and can benefit greatly from total hip arthroplasty.
      However, numerous procedural challenges and perioperative complications make
      these cases difficult. More specifically, femoral canal preparation and proper
      component placement can be particularly challenging due to focal medullary
      sclerosis caused by repeated vascular insults to the bone. This study describes
      the creation of an anterior metaphyseal cortical bone window to aid in
      identification of the true femoral canal and to facilitate femoral component
      implantation.

PMID- 22868078
TI  - Awareness on oral cancer in people with intellectual disability.

PMID- 22868079
TI  - PET/CT: Emphasis and current utility in oral cancer.

PMID- 22868080
TI  - Predictors of azoospermia and sperm recovery in patients with cancer.

PMID- 22868081
TI  - Live birth after blastocyst transfer following only 2 days of progesterone
      administration in an agonadal oocyte recipient.
AB  - In oocyte donation cycles where hormone replacement is given to recipients,
      progesterone administration is necessary to induce the luteal phase and
      synchronize the endometrium with the embryo stage. Most studies suggest that 5-7
      days of progesterone are needed to prepare the endometrium for a day-5 embryo
      transfer and provide optimal implantation rate. This paper reports a case where
      an agonadal oocyte recipient received only 2 days of progesterone prior to the
      embryo transfer of a day-5 embryo. She subsequently had a clinical pregnancy and
      a live birth.

PMID- 22868082
TI  - Association between XRCC1 single-nucleotide polymorphisms and infertility with
      idiopathic azoospermia in northern Chinese Han males.
AB  - X-ray repair cross-complementing group 1 (XRCC1) is a scaffold protein that plays
      a critical role in DNA base excision repair. To explore the association between
      XRCC1 single-nucleotide polymorphisms and infertility with idiopathic azoospermia
      in a northern Chinese Han population, PCR restriction fragment length
      polymorphism was used to genotype a SNP locus (rs25487) of XRCC1 in 112 patients
      with idiopathic azoospermia and 156 healthy controls. Furthermore, nucleotide
      sequences were sequenced. The results showed that, compared with GG genotype, the
      GA and GA+AA genotypes showed a significant association with an increased risk of
      idiopathic azoospermia (OR 2.119, 95% CI 1.245-3.606, P=0.005), (OR 2.052, 95% CI
      1.227-3.431, P=0.006) respectively. Meanwhile, the A allele frequency was
      significantly higher in azoospermic patients than that in controls (OR 1.472, 95%
      CI 1.029-2.105, P=0.034). The substitutions bring about an amino acid alteration:
      G->A changes the arginine residue into glutamine. In conclusion, the SNP locus
      rs25487 of XRCC1 could be a marker for genetic susceptibility to idiopathic
      azoospermia and the A allele might be a risk gene of idiopathic azoospermia in
      the northern Chinese Han population.

PMID- 22868084
TI  - Low-dose metronomic chemotherapy: from past experience to new paradigms in the
      treatment of cancer.
AB  - Low-dose metronomic (LDM) chemotherapy represents an emerging concept in the
      treatment of cancer. Directed against tumor cells and other types of cells, such
      as endothelial and immune cells, this treatment regimen alters the tumor
      microenvironment and suppresses innate features which support tumor growth.
      Ongoing Phase III clinical studies explore various applications of LDM
      chemotherapy, mostly combined with other anticancer agents, to act as
      complementary treatments to conventional maximum tolerated dose (MTD)
      chemotherapy. In this article we summarize preclinical and clinical experience
      with LDM chemotherapy, emphasizing the potential contribution of this new
      treatment modality to future paradigms in the systemic treatment of patients with
      cancer.

PMID- 22868085
TI  - Targeting treatment technologies to address specific stormwater pollutants and
      numeric discharge limits.
AB  - Stormwater treatment is entering a new phase with stormwater management systems
      being required to meet specific numeric objectives, as opposed to the historic
      approach of meeting guidance-document-provided percent removal rates. Meeting
      numeric discharge requirements will require designers to better understand and
      apply the physical, chemical, and biological processes underpinning these
      treatment technologies. This critical review paper focuses on the potential unit
      treatment operations available for stormwater treatment and outlines how to
      identify the most applicable treatment options based on the needed pollutant
      removal goals.

PMID- 22868086
TI  - A two and half-year-performance evaluation of a field test on treatment of source
      zone tetrachloroethene and its chlorinated daughter products using emulsified
      zero valent iron nanoparticles.
AB  - A field test of emulsified zero valent iron (EZVI) nanoparticles was conducted at
      Parris Island, SC, USA and was monitored for two and half years to assess the
      treatment of subsurface-source zone chlorinated volatile organic compounds
      (CVOCs) dominated by tetrachloroethene (PCE) and its chlorinated daughter
      products. Two EZVI delivery methods were used: pneumatic injection and direct
      injection. In the pneumatic injection plot, 2180 L of EZVI containing 225 kg of
      iron (Toda RNIP-10DS), 856 kg of corn oil, and 22.5 kg of surfactant were
      injected to remedy an estimated 38 kg of CVOCs. In the direct injection plot, 572
      L of EZVI were injected to treat an estimated 0.155 kg of CVOCs. After injection
      of the EZVI, significant reductions in PCE and trichloroethene (TCE)
      concentrations were observed in downgradient wells with corresponding increases
      in degradation products including significant increases in ethene. In the
      pneumatic injection plot, there were significant reductions in the downgradient
      groundwater mass flux values for PCE (>85%) and TCE (>85%) and a significant
      increase in the mass flux of ethene. There were significant reductions in total
      CVOC mass (86%); an estimated reduction of 63% in the sorbed and dissolved phases
      and 93% reduction in the PCE DNAPL mass. There are uncertainties in these
      estimates because DNAPL may have been mobilized during and after injection.
      Following injection, significant increases in dissolved sulfide, volatile fatty
      acids (VFA), and total organic carbon (TOC) were observed. In contrast, dissolved
      sulfate and pH decreased in many wells. The apparent effective remediation seems
      to have been accomplished by direct abiotic dechlorination by nanoiron followed
      by biological reductive dechlorination stimulated by the corn oil in the
      emulsion.

PMID- 22868087
TI  - Hospital-acquired listeriosis associated with sandwiches in the UK: a cause for
      concern.
AB  - BACKGROUND: Hospital-acquired outbreaks of listeriosis are not commonly reported
      but remain a significant public health problem. AIM: To raise awareness of
      listeriosis outbreaks that have occurred in hospitals and describe actions that
      can be taken to minimize the risk of foodborne listeriosis to vulnerable
      patients. METHODS: Foodborne outbreaks and incidents of Listeria monocytogenes
      reported to the Health Protection Agency national surveillance systems were
      investigated and those linked to hospitals were extracted. The data were analysed
      to identify the outbreak/incident setting, the food vehicle, outbreak
      contributory factors and origin of problem. FINDINGS: Most (8/11, 73%) foodborne
      outbreaks of listeriosis that occurred in the UK between 1999 and 2011 were
      associated with sandwiches purchased from or provided in hospitals. Recurrently
      in the outbreaks the infecting subtype of L. monocytogenes was detected in
      supplied prepacked sandwiches and sandwich manufacturing environments. In five of
      the outbreaks breaches in cold chain controls of food also occurred at hospital
      level. CONCLUSIONS: The outbreaks highlight the potential for sandwiches
      contaminated with L. monocytogenes to cause severe infection in vulnerable
      people. Control of L. monocytogenes in sandwich manufacturing and within
      hospitals is essential to minimize the potential for consumption of this
      bacterium at levels hazardous to health. Manufacturers supplying sandwiches to
      hospitals should aim to ensure absence of L. monocytogenes in sandwiches at the
      point of production and hospital-documented food safety management systems should
      ensure the integrity of the food cold chain.

PMID- 22868088
TI  - Hereditary cerebral small vessel diseases: a review.
AB  - Cerebral microangiopathies are responsible of a great number of strokes. In the
      recent years advances in molecular genetics identified several monogenic
      conditions involving cerebral small vessels and predisposing to ischemic and/or
      hemorrhagic stroke and diffuse white matter disease leading to vascular dementia.
      Clinical features and diagnostic clues of these conditions, [cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts
      and leukoencephalopathy (CARASIL), COL4A1-related cerebral small vessel diseases,
      autosomal dominant retinal vasculopathy with cerebral leukodystrophy (AD-RVLC),
      and Fabry's disease] are here reviewed. Albeit with variable phenotypes and with
      different defective genes, all these disorders produce arteriopathy and
      microvascular disintegration with changes in brain functions. Specific diagnostic
      tools are recommended, genetic analysis being the gold standard for the
      diagnosis.

PMID- 22868089
TI  - ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor
      in hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) confines a group of heterogeneous
      neurodegenerative disorders characterized by progressive spasticity and lower
      limb weakness. Age of onset is highly variable even in familial cases with known
      mutations suggesting that the disease is modulated by other yet unknown
      parameters. Although progressive gait disturbances, lower limb spasticity and
      extensor plantar responses are hallmarks of HSP these characteristics are also
      found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis
      (ALS). HSP has been linked to ALS and frontotemporal degeneration with motor
      neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been
      found in an HSP subtype, and TDP-43 are found in abundance in pathological
      inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene
      ATXN2), a polyglutamine containing protein elongated in spinocerebellar ataxia
      type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal
      and cell models. Finally, it has been shown that ATXN2 with non-pathogenic
      intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract)
      is a genetic risk factor of ALS. Considering the similarities in the disease
      phenotype and the neuropathological link between ALS and HSP we hypothesized that
      intermediate-length CAG/CAA repeats in ATXN2 could be a modulator of HSP. We show
      that in a cohort of 181 HSP patients 4.9 % of the patients had intermediate
      length CAG/CAA repeats in ATXN2 which was not significantly different from the
      frequencies in a Danish control cohort or in American and European control
      populations. However, the mean age of onset was significantly lower in HSP
      patients with intermediate-length CAG/CAA repeats in ATXN2 compared to patients
      with normal length repeats. Based on these results we conclude that ATXN2 is most
      likely not a risk factor of HSP, whereas it might serve as a modulator of age of
      onset.

PMID- 22868090
TI  - Cerebrovascular lesions in elderly Japanese patients with Alzheimer's disease.
AB  - OBJECTIVE: Cerebrovascular lesions (CVLs) are known to play important roles in
      the pathophysiology underlying Alzheimer's disease (AD), especially in elderly AD
      cases. The present study was conducted to elucidate the relationship between the
      CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD.
      SUBJECTS AND METHODS: The CVLs such as lacunar infarcts, old microbleeds (OMBs),
      white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed
      in relation to the risk factors in 120 Japanese patients with probable AD. Their
      mean age was 75.6 years. The subjects were divided into two age groups: young-old
      group (YOG) consisting of 55 cases being younger than 75 years and old-old group
      (OOG) consisting of 65 cases being 75 years or older. RESULTS: In overall
      analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases
      (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed
      lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial
      siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in
      YOG, and were also more frequently observed in those with 2 or more VRFs than
      those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and
      in those with more VRFs. CONCLUSION: The CVLs including lacunes, WMLs, and OMBs
      were present more than 90% of elderly Japanese patients with AD. As the severity
      of CVLs was associated with VRFs and age, VRFs may modify clinical presentation
      of elderly AD patients.

PMID- 22868091
TI  - Non-demyelinating, reversible conduction failure in a case of pharyngeal-cervical
      brachial weakness overlapped by Fisher syndrome.
AB  - Pathophysiologically, Guillain-Barre syndrome is divided into demyelinating and
      axonal subtypes. Recent studies have shown that serial nerve conduction studies
      (NCSs) are required to differentiate a demyelination-remyelination
      pathophysiology from one with axonal nodal reversible conduction failure. Cases
      with an overlap of pharyngeal-cervical-brachial weakness and Fisher syndrome
      (PCB/FS) are uncommon; the NCS findings of such cases have not been well
      described and the evolution of the NCS findings has not been previously studied.
      We describe the clinical features and serial NCS findings of a patient with
      PCB/FS. The evolution of abnormalities in NCS reflected a clinical pattern of
      weakness that progressed from the top of the body and descended toward the legs,
      and terminated before reaching the legs. The amplitudes of motor and sensory
      potentials were decreased, as is consistent with acute motor-sensory axonal
      neuropathy. However, the amplitudes recovered without the appearance of dispersed
      potentials seen in remyelination, implicating the pathophysiology of nodal
      reversible conduction failure. Together with the electrophysiological evidence of
      the pathophysiology of nodal reversible conduction failure in previously reported
      PCB patients and FS patients, our case suggests that PCB, FS and PCB/FS fall in a
      continuous spectrum with axonal GBS subtypes.

PMID- 22868092
TI  - Differential characteristics of the aging process and the vascular cognitive
      impairment in the organization of memory retrieval.
AB  - Early identification of cognitive impairment in patients with chronic cerebral
      vascular disorders can allow for evaluating the time course of the disease up to
      the phase of conversion to dementia. The specific indicators of pathological
      cognitive decline should be identifiable vs. the concurrent age-associated
      changes in memory which accompany the aging process. We propose a method which
      evaluates memory dysfunctions in vascular cognitive impairment (VCI) as distinct
      from age-associated memory changes. This method is based on a serial learning
      task of concrete frequent words and it consists in controlling the effects of age
      and cerebral pathology on various characteristics of immediate recall, including
      serial effect and productivity. Ninety participants underwent a between group
      examination: younger adults vs. older adults vs. VCI patients who were
      outpatients with a positive history for chronic cerebral vascular disorder,
      positive neuroimaging examination, a Hachinski ischemic score >= 5 and a mild to
      moderate cognitive impairment. VCI patients show a reduced efficiency of
      retrieval and recall organization while, age-associated cognitive changes consist
      of a modification of the serial position effects. In particular, VCI patients, as
      distinct from same-age normal cases, can perform an only partial utilization of
      the inherent structure of the memory task with a very limited efficiency of
      relearning which is not sufficiently supported by the facilitating factors due to
      task repetition.

PMID- 22868093
TI  - Identifying irradiated oysters by luminescence techniques (TL & PSL).
AB  - This study shows an exhaustive comparison of different methods, based on
      luminescence techniques, to identify X-ray irradiated oysters at five different
      dose levels in the range 0.1-2 kGy and suggests a simple, fast and sequential
      routine analysis protocol. A total number of 50 oysters from North Sea, including
      10 control samples, were analysed by using two photo-stimulated luminescence
      (PSL) methods (named A and B) and three thermoluminescence (TL) methods (named C,
      D and E), either on constituents or contaminating minerals from shells and
      intestines. Setting a lower threshold value T1 (1000 counts/60s) all of control
      specimens gave negative screening results while photo counts from irradiated
      samples were found to be higher than upper threshold T2 (4000 counts/60s), except
      at the lowest dose level 0.1 kGy for procedure A. All PSL calibrated analysis
      were successful and a sensitivity index was also determined to better classify
      obtained data according to the revised European Standard (EN 13751:2009). TL
      ratios, Glow 1 over second Glow 2, the latter after irradiating at 1 kGy and
      remeasuring the same minerals for each sample, showed values less than 0.1
      related to untreated samples or higher than 0.1 for irradiated ones. Reported
      procedures were also tested over 60 days, longer than oyster shelf life
      confirming the applicability and feasibility of the proposed methods.

PMID- 22868094
TI  - Phytochemical compositions, and antioxidant properties, and antiproliferative
      activities of wheat flour.
AB  - Ten soft wheat varieties grown in Maryland were compared for their phytochemical
      compositions, antioxidant properties and antiproliferative activities. Free
      radical scavenging capacities were examined against DPPH(.), oxygen, hydroxyl and
      ABTS(.+) radicals. Significant radical scavenging capacities were detected in all
      wheat flour extracts. Total phenolic content ranged from 1.66 to 2.01 mg of GAE/g
      wheat flour. The wheat flours contained 172.91-297.55 MUg/g insoluble bound
      ferulic acid, contributing 89.74-94.29% of total ferulic acid on a per weight
      basis. The concentrations of lutein and zeaxanthin were 0.27-0.46 and 0.08-0.13
      MUg/g, respectively. In addition, the wheat flours had 0.30-0.59 and 0.07-0.29
      MUg/g alpha- and delta-tocopherols, respectively. Four wheat flour extracts were
      further examined for their antiproliferative activities. The Jamestown wheat
      flour showed significant antiproliferative activity against both HT-29 and Caco-2
      colon cancer cells at the initial treatment concentration of 50 mg flour
      equivalents/ml, while USG3555 flour showed inhibitive effect only in HT-29 cancer
      cells, suggesting the different and possible selective antiproliferative property
      of the wheat flours. These results may be used to direct the breeding effects to
      produce soft winter wheat varieties with improved health properties.

PMID- 22868095
TI  - In vitro antioxidant and anti-inflammatory activities of 1-dehydro-[6]
      gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin.
AB  - Hexahydrocurcumin, 1-dehydro-[6]-gingerdione, 6-dehydroshogaol and 6-shogaol were
      evaluated for their antioxidant and anti-inflammatory activities in the present
      study. The relative antioxidant potencies of ginger compounds decreased in
      similar order of 1-dehydro-[6]-gingerdione, hexahydrocurcumin>6-shogaol>6
      dehydroshogaol in both 1,1-diphenyl-2-picyrlhydrazyl (DPPH) radical-scavenging
      and trolox equivalent antioxidant capacity (TEAC) assays. All tested compounds
      could attenuate lipopolysaccharide (LPS)-elicited increase of prostaglandin E2
      (PGE(2)) in murine macrophages (RAW 264.7) in a concentration-dependent manner
      but hexahydrocurcumin of 7MUM and 6-shogaol of 7MUM. The strongest inhibitory
      effect was observed for 6-dehydroshogaol and 6-shogaol at 14MUM with the
      inhibition of 53.3% and 48.9%, respectively. Furthermore, both 6-dehydroshogaol
      and 1-dehydro-[6]-gingerdione significantly suppressed the expression of
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a
      concentration-dependent fashion. These results contribute to our theoretical
      understanding of the potential beneficial effects of consuming ginger as a food
      and/or dietary supplement.

PMID- 22868096
TI  - Classification of Chinese honeys according to their floral origin by near
      infrared spectroscopy.
AB  - The feasibility of near infrared (NIR) spectroscopy and multivariate analysis as
      tools to classify Chinese honey samples according to their different floral
      origins was explored. Five kinds of honey, namely, acacia, linden, rape, vitex
      and jujube, were analysed using a NIR spectrophotometer with a fibre optic probe.
      Classification models based on the NIR spectra were developed using Mahalanobis
      distance discriminant analysis (MD-DA) and a back propagation artificial neural
      network (BP-ANN). By the MD-DA model, total correct classification rates of 87.4%
      and 85.3% were observed for the calibration and validation samples, respectively,
      while the ANN model resulted in total correct classification rates of 90.9% and
      89.3% for the calibration and validation sets, respectively. By ANN, the
      respective correct classification rates of linden, acacia, vitex, rape and jujube
      were 97.1%, 94.3%, 80.0%, 97.1%, and 85.7% in calibration, and 100%, 93.3%,
      80.0%, 100%, and 73.3% in validation. The results indicated that NIR combined
      with a classification technique could be a suitable technology for the
      classification of Chinese honeys from different botanical origins.

PMID- 22868097
TI  - Comparison of polarimetry and crown ether-based HPLC chiral stationary phase
      method to determine (L)-amino acid optical purity.
AB  - Although various pharmacopoeias provide titration methods to assay (L)-amino acid
      content, none of these methods distinguish between (L)- and (D)-amino acids and
      do not consider the presence of enantiomeric impurities. Consequently, these
      methods are limited in scope to describe the relationship between content and
      specific rotation, [alpha]. In this study, the US Pharmacopoeia method was
      compared with the crown ether-based high performance liquid chromatographic
      (HPLC) chiral stationary phase (CSP) method to determine (L)-amino acid content
      and specific rotation. The (L)-amino acid content specified by the US
      Pharmacopoeia method was not consistent with the specific rotation in the
      presence of enantiomeric impurities, whereas the HPLC-CSP method was very
      effective for determining the (L)-amino acid content and the optical purity. The
      other advantage is that the HPLC-CSP method requires amino acid samples of quite
      low concentration (as low as 1 MUg/mL), whereas the pharmacopoeia method requires
      higher concentrations (20-110 mg/mL).

PMID- 22868098
TI  - Structure-quality relationship in commercial pasta: a molecular glimpse.
AB  - Presence and stability of a protein network was evaluated by fluorescence
      spectroscopy, by protein solubility studies, and by assessing the accessibility
      of protein thiols in samples of commercial Italian semolina pasta made in
      industrial plants using different processes. The pasting properties of starch in
      each sample were evaluated by means of a viscoamylograph. Magnetic resonance
      imaging (MRI) was used to evaluate water distribution and water mobility in dry
      pasta, and at various cooking times. The molecular information derived from these
      studies was related to sensory indices, indicating that protein reticulation was
      dependent on the process conditions, which affected water penetration,
      distribution, and mobility during cooking. Products with a crosswise gradient of
      water mobility once cooked had the best sensory scores at optimal cooking time,
      whereas products with a less compact protein network performed better when
      slightly overcooked.

PMID- 22868099
TI  - Hypocholesterolaemic effect of yoghurt containing Bifidobacterium
      pseudocatenulatum G4 or Bifidobacterium longum BB536.
AB  - The effect of a yoghurt supplement containing Bifidobacterium pseudocatenulatum
      G4 or Bifidobacterium longum BB536 on plasma lipids, lipid peroxidation and the
      faecal excretion of bile acids was examined in rats fed a cholesterol-enriched
      diet. After 8 weeks, the rats in the positive control (PC) group who were fed the
      cholesterol-enriched diet showed significant increases in plasma total
      cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and malondialdehyde
      (MDA). However, groups fed a cholesterol-enriched diet supplemented with yoghurt
      containing B. pseudocatenulatum G4 or B. longum BB536 had significantly lower
      plasma TC, LDL-C, very-low-density lipoprotein (VLDL) cholesterol, and MDA than
      had the PC group after 8 weeks of treatment. In addition, faecal excretion of
      bile acids was markedly increased in the rats fed the yoghurt containing B.
      pseudocatenulatum G4 or B. longum BB536 as compared to the PC and NC groups.

PMID- 22868100
TI  - Determination of ascorbic acid levels in food samples by using an ionic liquid
      carbon nanotube composite electrode.
AB  - A novel carbon composite electrode consisted of ionic liquid n-octylpyridinum
      hexafluorophosphate (OPFP) and single-walled carbon nanotube (SWCNT) was
      fabricated and investigated. This electrode combined the advantages of ionic
      liquid and SWCNT together with the "bulk" composite electrode. Compared with
      other composite electrodes using graphite or paraffin oil, the ionic liquid-SWCNT
      (IL-SWCNT) composite electrode exhibited remarkable increase in the electron
      transfer rate for electroactive compound and significant decrease in the
      overpotential for ascorbic acid oxidation reaction. Based on the greatly enhanced
      electrocatalytic activity for the oxidation of ascorbic acid, a wide linear
      detection range from 3.0 MUM to 4.2 mM with a low detection limit of 1.0 MUM was
      obtained. Furthermore, the IL-SWCNT electrode was applied to determine ascorbic
      acid levels in real food samples. Experimental results showed that the proposed
      electrode could be used as an effective and sensitive sensor for direct detection
      of ascorbic acid.

PMID- 22868101
TI  - Determination of ochratoxin A in wines by capillary liquid chromatography with
      laser induced fluorescence detection using dispersive liquid-liquid
      microextraction.
AB  - A method based on reverse phase capillary high performance liquid chromatography
      (capillary HPLC) coupled to laser-induced fluorescence detection (LIF) has been
      proposed for the determination of ochratoxin A (OTA) in wine samples. An anionic
      micellar medium was added to the mobile phase for increasing the fluorescence
      intensity and peak efficiency. Dispersive liquid-liquid microextraction (DLLME)
      has been used as a simple and efficient sample pretreatment method for the
      analysis of OTA in wines, being optimised by means of experimental design. The
      limit of detection was 5.5 ng L(-1) (3 * S/N) and recoveries for different wines
      ranged from 91.7 to 98.1%. The proposed methodology could be classified as a
      green analytical chemistry alternative, combining the low organic solvent volumes
      required in the DLLME with the reduced consumption of mobile phase in capillary
      HPLC. The use of LIF as detector provided an extremely sensitive method for the
      determination of OTA in wines.

PMID- 22868102
TI  - Phospholipase D (PLD) catalyzed synthesis of phosphatidyl-glucose in biphasic
      reaction system.
AB  - Presence of saccharides in glycophospholipids may increase its potential to form
      supramolecular structures, which are not only stable for an extended period of
      time as compared to other PLs like phosphatidylcholine, but may also confer an
      antioxidative property. Most syntheses routes for glycophospholipid involved the
      usage of toxic chemicals or solvents, complicated steps and low yield. The
      present work attempted to develop an enzymatic method for the production of
      glycophospholipids. Phosphatidyl-glucose (PL-Glu) was synthesized as a model
      glycophospholipid. The effects of organic solvents, water content, substrate
      ratio, pH and temperature on glycophospholipid yield (mol%) were examined in this
      study. Under optimum reaction conditions, more than 95 mol% of PL-Glu was
      obtained in 1.5 h. The conversion rate is significantly higher than previously
      reported findings. The established model reaction system in the present work was
      used to synthesize other types of glycophospholipid.

PMID- 22868103
TI  - Enzyme immunoassay and liquid chromatography-fluorescence detection for amikacin
      in raw milk.
AB  - An enzyme immunoassay and a liquid chromatography (LC) method for amikacin (AMK)
      in raw milk were developed in this study. Anti-AMK antibody was prepared by
      immunizing rabbits with AMK-BSA conjugate. The developed immunoassay exhibited an
      IC(50) value of 1.30 ng/mL and the spiked recoveries at 25-1000 ng/mL ranged from
      69.8% to 93.3% with coefficients of variation (CVs) of 8.5-17.6%. For LC
      analysis, AMK was derivatized with 9-fluorenylmethyl chloroformate, which was
      followed by C8 column separation and fluorescence detection. By trichloroacetic
      acid extraction and MCX column purification, the recoveries at spiked
      concentrations of 500-5000 ng/mL were 80.7-91.3% with CVs less than 6.3%. The two
      methods can be selectively used for rapidly screening or quantitatively
      determining AMK in raw milk.

PMID- 22868105
TI  - Generation of potentially bioactive ergosterol-derived products following pulsed
      ultraviolet light exposure of mushrooms (Agaricus bisporus).
AB  - The production of vitamin D(2) from ergosterol in mushrooms upon exposure to
      ultraviolet (UV) irradiation has been well established in recent years. However,
      the effect of this treatment on the generation of non-vitamin D(2) products of
      ergosterol in mushrooms has not been reported. In this study, the ergosterol
      derived photoproducts previtamin D(2), lumisterol(2) and tachysterol(2) were, for
      the first time, identified and quantified in white button mushrooms (Agaricus
      bisporus) following treatment with pulsed UV (PUV) light. Mushrooms were treated
      with up to 60pulses of PUV irradiation and the formation of major photoproducts
      was observed to increase as a function of dose. Vitamin D(2) was the most
      abundant product, followed by previtamin D(2), lumisterol(2) and tachysterol(2)
      in order of decreasing abundance. Untreated mushroom samples were not observed to
      contain detectable levels of any photoproduct. This study shows for the first
      time the production of these photoproducts in UV irradiated mushrooms. A complete
      understanding of the potential biological significance of these products remains
      to be seen.

PMID- 22868104
TI  - Functional components in Luffa cylindrica and their effects on anti-inflammation
      of macrophage cells.
AB  - The objectives of this study were to determine the distribution of functional
      components in peel and pulp of Luffa cylindrica and evaluate their anti
      inflammatory activity on RAW 264.7 murine macrophage cells. Phenolics and
      flavonoids were present in abundant amounts in aqueous extract of peel, but in
      ethyl acetate extracts of peel, oleanolic acid, carotenoids and chlorophylls
      dominated. Both ethanol and ethyl acetate extracts in peel and pulp decreased
      production of nitric oxide in LPS-induced RAW 264.7 cells, whereas the ethanol
      extract mitigated secretion of prostaglandin E(2). Furthermore, all the extracts
      significantly inhibited IL-6 production, but remained ineffective in retarding
      generation of IL-1beta and TNF-alpha. Ethyl acetate extract of peel reduced
      expression of inducible nitric oxide synthase, but enhanced expression of
      cyclooxygenase 2. Both ethyl acetate extracts of peel and pulp mitigated
      expression of p-IkappaBalpha, while the latter attenuated expression of p-ERK,
      and all the extracts failed to inhibit JNK phosphorylation.

PMID- 22868106
TI  - Rapid and selective quantification of L-theanine in ready-to-drink teas from
      Chinese market using SPE and UPLC-UV.
AB  - An ultra performance liquid chromatography (UPLC) method combined with solid
      phase extraction (SPE) sample pre-treatment was developed and validated for the
      rapid quantification of L-theanine in ready-to-drink (RTD) teas. UPLC analysis of
      twenty-seven RTD teas from the Chinese market revealed that the L-theanine levels
      in various types of RTD teas were significantly different. RTD green teas were
      found to contain highest mean L-theanine level (37.85+/-20.54 mg/L), followed by
      jasmine teas (36.60+/-12.08 mg/L), Tieguanying teas (18.54+/-3.46 mg/L) black
      teas (16.89+/-6.56), Pu-erh teas (11.31+/-0.90 mg/L) and oolong teas (3.85+/-2.27
      mg/L). The ratio of total polyphenols content to L-theanine content could be used
      as a featured parameter for differentiating RTD teas. L-theanine in RTD teas
      could be a reliable quality parameter that is complementary to total polyphenols.

PMID- 22868107
TI  - A defensin-like peptide from Phaseolus vulgaris cv. 'King Pole Bean'.
AB  - A 5447 Da antifungal peptide with an N-terminal sequence highly homologous to
      plant defensins was purified from Phaseolus vulgaris cv. 'King Pole Bean' by
      anion-exchange chromatography on Q Sepharose and FPLC-gel filtration on Superdex
      75. The isolated peptide inhibited growth of a number of fungal species,
      including Mycosphaerella arachidicola, Saccharomyces cerevisiae and Candida
      albicans, with IC(50) values of 3.9, 4.0 and 8.4 MUM, respectively. Using the
      membrane non-permeable DNA-binding dye SYTOX green, it was found that the peptide
      increased the cell membrane permeability of M. arachidicola, S. cerevisiae and C.
      albicans.

PMID- 22868108
TI  - Effects of 1-MCP on chlorophyll degradation pathway-associated genes expression
      and chloroplast ultrastructure during the peel yellowing of Chinese pear fruits
      in storage.
AB  - The peel yellowing is an important pigment physiological process of green fruit
      ripening, which mainly results from chlorophyll degradation in the fruit peel. In
      this work, two typical cultivars with different ripening speed, a slow ripening
      pear 'Emerald' (Pyrus bretschneideri Rehd. cv. Emerald) and a fast ripening
      'Jingbai' (Pyrus ussuriensis Maxim. cv. Jingbai) were used to investigate the
      molecular mechanism of chlorophyll degradation in pear yellowing/ripening during
      postharvest storage. The fruits after harvest were treated with 1
      methylcyclopropene (1-MCP), an ethylene action inhibitor at 1.0 MULl(-1) to
      determine its effect on chloroplast ultrastructure and the expression of
      chlorophyll degradation associated genes in peel tissues. Our results show that
      the pears treated with 1-MCP had a lower ethylene production rate and higher
      chlorophyll content compared to those of untreated fruit. The more intact
      chloroplasts with well-organised grana thylakoids and small plastoglobuli were
      maintained in the peel of 1-MCP treated fruit for up to 30 and 15 d in 'Emerald'
      and 'Jingbai', respectively. The expression of chlorophyll degradation associated
      genes: pheophorbide a oxygenase (PAO), non-yellow colouring (NYC), NYC1-like
      (NOL), stay-green 1(SGR1), was suppressed, while no significant change was found
      in chlorophyllase 1 (CHL1) and red chlorophyll catabolite reductase (RCCR) in
      both cultivar fruits treated with 1-MCP. These results suggest that 1-MCP can
      delay chlorophyll degradation by inhibiting ethylene production and suppressing
      the gene expression of PAO, NYC, NOL and SGR1, which are closely associated with
      chlorophyll catabolic pathway.

PMID- 22868109
TI  - Co-occurrence and risk assessment of mycotoxins in food and diet from
      Mediterranean area.
AB  - The contents of 14 mycotoxins were studied in samples of different cereals and
      cereal products from four countries of the Mediterranean region. Two hundred and
      sixty-five samples from Spain, Italy, Morocco and Tunisia were analysed. Samples
      were extracted with matrix solid-phase dispersion (MSPD) and determined by liquid
      chromatography-tandem mass spectrometry with a triple quadrupole mass analyser.
      The percentage of total samples contaminated was 53%. The frequency of
      contaminated samples from Spain, Italy, Tunisia and Morocco was 33%, 52%, 96% and
      50%, respectively. Nivalenol and beauvericin were the most predominant
      mycotoxins. This is the first international report to study the presence of
      several mycotoxins in different types of cereal (rice, wheat, maize, rye, barley,
      oat, spelt and sorghum) and cereal products (snacks, pasta, soup, biscuits and
      flour) from the Mediterranean area, estimate the intake of mycotoxins and
      evaluate the risk assessment.

PMID- 22868110
TI  - Determination of (fluoro)quinolones in eggs by liquid chromatography with
      fluorescence detection and confirmation by liquid chromatography-tandem mass
      spectrometry.
AB  - A multiresidue analytical procedure for determination of seven fluoroquinolones
      (marbofloxacin, norfloxacin as internal standard, ciprofloxacin, danofloxacin,
      enrofloxacin, sarafloxacin and difloxacin), and three quinolones (oxolinic acid,
      nalidixic acid and flumequine) in eggs is presented. The procedure is based on
      dispersive solid-phase extraction technique with acetonitrile as extractant.
      Norfloxacin and ciprofloxacin - d8 were used as internal standards to quantify
      the (fluoro)quinolones. Analyses were realised by LC-FLD for screening and LC
      MS/MS for confirmatory purposes. The whole procedure was evaluated according to
      the Commission Decision 2002/657/EC. Specificity, decision limit (CCalpha),
      detection capacity (CCbeta), recovery (absolute and relative), precision
      (repeatability and reproducibility) were determined during validation process.
      Recoveries (relative) for the LC-FLD screening determination ranged from 85% to
      93%, repeatability and reproducibility were in the range of 5-9% to 9-16%,
      respectively. CCalpha and CCbeta were 13-37 and 17-43 MUg/kg pending on analite.
      For the LC-MS/MS confirmatory method, the relative recoveries were satisfactory
      (92-99%) with repeatability and reproducibility in the range of 4-7% to 6-12%,
      respectively. CCalpha and CCbeta were 3-7 and 7-11 MUg/kg depending on the
      analite. The results of both prepared methods showed these analytical procedures
      simple, rapid, sensitive and suitable for routine control of eggs.

PMID- 22868111
TI  - Inhibitory effects of water extract from longan twigs on mutation and nitric
      oxide production.
AB  - This study examines the inhibitory effects of water extract from longan twigs
      (WLTs) on mutation and nitric oxide (NO) production. The results show that WLT
      inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen, and
      4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward Salmonella typhimurium
      TA 98 and TA 100. In addition, WLT in the range 0-0.6 mg/ml showed radical
      scavenging, reducing activities and chelating activity, as well as decreased
      lipid oxidative damage. Meanwhile, WLT also inhibited tyrosinase activity and NO
      generation in lipopolysaccharide (LPS) stimulated macrophages. High performance
      liquid chromatography analysis suggests that the major phenolic constituents in
      WLT are epicatechin, ellagic acid and gallic acid. These bioactive components may
      contribute to the protective effects of WLT. Our data suggests that WLT can be
      applied to antimutation, anti-inflammation and antityrosinase.

PMID- 22868112
TI  - Application of gold nanoparticles/TiO2 modified electrode for the
      electrooxidative determination of catechol in tea samples.
AB  - A gold nanoparticles/TiO(2) composite modified Indium tin oxide (ITO) electrode
      has been constructed to study the electrochemical behaviour of catechol (CC) and
      hydroquinone (HQ) using cyclic voltammetry and differential pulse voltammetry
      (DPV). Increasing of separation of the oxidative peak potentials and peak current
      for CC and HQ in pH 6.0 phosphate buffer solution (PBS), make it suitable for
      selected determination of CC. After the optimization of the conditions, CC was
      determined by DPV and the linear range is from 1.0*10(-7) to 5.0*10(-4) mol L(-1)
      with a correlation coefficient of 0.999 and limit of detection as 5.0*10(-8) mol
      L(-1). Interference and stability study showed a satisfactory result. The
      proposed method has been applied to determine catechol in tea samples, and
      comparing with the chromatography the results are satisfactory.

PMID- 22868113
TI  - Evaluation of the in vitro and in vivo protective effects of unfermented and
      fermented Rhizoma coptidis formulations against lipopolysaccharide insult.
AB  - Lipopolysaccharide (LPS) can produce endotoxic shock by triggering the systemic
      inflammatory response. Here, we evaluated the in vitro and in vivo protective
      effects of unfermented and fermented Rhizoma coptidis (RC and FRC, respectively)
      against LPS-insult. In general, RC suppressed the LPS-induced expression of key
      inflammatory mediators in RAW264.7 cells, in a dose-dependent manner. Notably,
      FRC at a 20 MUg/ml dose in combination with the probiotic used for fermentation
      showed more potent in vitro anti-inflammatory activities than that exhibited by
      the corresponding dose of RC. Moreover, oral treatment with FRC in association
      with the probiotic, but not oral administration of RC, significantly attenuated
      blood endotoxin and C-reactive protein (CRP) levels, and gut permeability, and
      significantly augmented the intestinal population of Bifodobacterium spp. and
      Lactobacillus spp. in LPS-treated animals. Our results demonstrate the beneficial
      impact of fermented RC in combination with the associated probiotic in combating
      LPS-insult both in vitro and in vivo.

PMID- 22868114
TI  - Nutritional and antioxidant profiles of pumpkin (Cucurbita pepo Linn.) immature
      and mature fruits as influenced by NPK fertilizer.
AB  - This study evaluated the influence of NPK fertilizer on protein, fibre, ash, fat,
      carbohydrate, antioxidant activities and antioxidant phenolic compounds in
      immature and mature fruits of pumpkin. The treatment consisted of six NPK levels
      (0, 50, 100, 150, 200 and 250 kg/ha), and was replicated six times in a
      randomized complete block design (RCBD). Proximate analysis and antioxidant
      assays were done using standard analytical methods. At control and lower NPK
      rates, the proximate compositions and antioxidant profile of pumpkin fruits
      decreased with increasing NPK fertilizer. Between the control and the highest
      fertilizer rate, proximate compositions decreased by 7-62% while the antioxidant
      profile decreased by 13-79% for both immature and mature fruits. Across all the
      measured parameters, mature fruit had higher proximate contents and higher
      antioxidant concentrations. For the high health value of pumpkin fruits to be
      maintained, little or no NPK fertilizer should be applied.

PMID- 22868115
TI  - Accelerated shelf-life testing of quality loss for a commercial hydrolysed hen
      egg white powder.
AB  - In recent years, due to the specific health benefits associated with bioactive
      peptides and the reduction of protein allergenicity by enzymatic hydrolysis, the
      utilisation of protein hydrolysates in functional foods and beverages for both
      protein supplementation and clinical use has significantly increased. However,
      few studies have explored the moisture-induced effects on food protein
      hydrolysates, and the resulting changes in the structure and texture of the food
      matrix as well as the loss in functional properties of bioactive peptides during
      storage. The main purpose of this study is to determine the influence of water
      activity (a(w)) on the storage quality of a commercial spray-dried hydrolysed hen
      egg white powder (HEW). During storage at 45  degrees C for two months at
      different a(w)s (0.05-0.79), the selected physicochemical properties of the HEW
      samples were analysed. Overall, the effect of a(w) on the colour change of HEW at
      45  degrees C for one month was similar to that of HEW after four months at 23 
      degrees C due to the presence of a small amount of glucose in HEW. Several
      structural changes occurred at a(w)s from 0.43 to 0.79 including agglomeration,
      stickiness and collapse. Kinetic analysis showed a first-order hyperbolic model
      fit for the change in the L(*) value, the total colour difference (DeltaE(*)) and
      the fluorescence intensity (FI). There was a high correlation between colour
      change and fluorescence, as expected for the Maillard reaction. The reduction in
      the remaining free amino groups was about 5% at a(w) 0.50 and 6% at a(w) 0.79
      after one month storage. In summary, during storage, the Maillard reaction and/or
      its resulting products could decrease the nutritional value and the quality of
      HEW.

PMID- 22868116
TI  - Beer fingerprinting by Matrix-Assisted Laser Desorption-Ionisation-Time of Flight
      Mass Spectrometry.
AB  - A method allowing parallel fingerprinting of proteins and maltooligosaccharides
      directly from untreated beer samples is presented. These two classes of compounds
      were detected by Matrix-Assisted Laser Desorption-Ionisation-Time of Flight-Mass
      Spectrometry (MALDI-TOF-MS) analysis of beer mixed with 2,5-dihydroxybenzoic acid
      solution. The maltooligosaccharide profiles acquired from the MALDI sample spot
      center were not found characteristic for beers of different source and
      technology. On the other hand, according to profiles containing protein signals
      acquired from crystals formed on the border of the MALDI sample spot, we were
      able to distinguish beer samples of the same brand produced by different
      breweries. The discriminatory abilities of the method were further examined on a
      set of 17 lager beers, where the fingerprints containing protein signals enabled
      resolution of majority of examined brands. We propose MALDI-TOF-MS profiling as a
      rapid tool for beer brewing technology process monitoring, quality control, and
      determination of beer authenticity.

PMID- 22868117
TI  - Isolation and identification of two novel umami and umami-enhancing peptides from
      peanut hydrolysate by consecutive chromatography and MALDI-TOF/TOF MS.
AB  - Peanut hydrolysate produced by crude protease extract from Aspergillus oryzae HN
      3.042 was found to elicit intense umami and umami-enhancing effect. Taste
      profiles, amino acid and organic acid composition of peanut hydrolysate and its
      separation fractions by ultrafiltration were evaluated. The results revealed that
      peanut hydrolysate was mainly low molecular weight compounds. Fractions of 1-3
      kDa and below 1 kDa prominently contributed to the umami taste and umami
      enhancing effect of the peanut hydrolysate. The two fractions were further
      purified, using gel filtration chromatography and reverse-phase high-performance
      liquid chromatography (RP-HPLC), in combination with sensory evaluation, to
      obtain a umami peptide and umami-enhancing peptide. The active peptides were
      identified as Ser-Ser-Arg-Asn-Glu-Gln-Ser-Arg (SSRNEQSR, 963.9 Da) and Glu-Gly
      Ser-Glu-Ala-Pro-Asp-Gly-Ser-Ser-Arg (EGSEAPDGSSR, 1091.1 Da), by MALDI-TOF/TOF
      MS, respectively.

PMID- 22868118
TI  - Hydrolysis and formation of volatile esters in New Zealand Sauvignon blanc wine.
AB  - The evolution of the varietal thiol 3-mercaptohexanol acetate (3MHA) and other
      key aroma compounds has been monitored in New Zealand Sauvignon blanc wines
      stored for 1 year at three different temperatures (5, 10 and 18  degrees C). The
      main processes that occurred in the Sauvignon blanc wines during bottle ageing
      were hydrolysis of 3MHA and other acetate esters, hydrolysis of ethyl esters of
      fatty acids, and the formation of ethyl esters of branched acids. The kinetic
      parameters of ester hydrolysis, including reaction rate constants and activation
      energies, were determined, which allow prediction of future wine composition
      based upon storage temperature and time. It was found that 3MHA had the highest
      reaction rate constant, meaning that this compound is the most unstable,
      particularly at higher storage temperatures, and that it disappeared very fast
      during wine storage.

PMID- 22868119
TI  - Multi-element analysis of mineral and trace elements in medicinal herbs and their
      infusions.
AB  - Twelve mineral and trace elements (Al, B, Ba, Fe, Zn, Mn, Mg, K, Na, P, Cu, Sr,
      and Ca) were determined in the herbs and their infusions consumed for medical
      purposes in Poland such as chamomile (Matricaria chamomilla L.), peppermint
      (Mentha xpiperita), melissa (Melissa officinalis), sage (Salvia officinalis),
      nettle (Urtica dioica), linden (Tilia vulgaris) and St. John's wort (Hypericum
      calycinum). Dry digestion procedure for total concentration and wet digestion
      procedure for infusions were applied under optimized conditions for dissolution
      of medicinal herbs. Element concentrations in herbs and their infusions were
      determined by ICP-OES. The accuracy and precision were verified against NCS DC
      73349 - bush branches and leaves certified reference material. The result of
      total concentrations of elements in herb leaves shows that all herbs contain most
      of the elements, except K and P, in the MUg/g range, and that elemental
      concentrations varied widely. Moreover, on the basis of experimental results for
      the extraction efficiencies, the elements in herb infusions were classified into
      three specific groups: highly-extractable (>55%) including K; moderately
      extractable (20-55%) including Mg, Na, P, B, Zn and Cu and poorly-extractable
      (<20%) including Al, Fe, Mn, Ba, Ca and Sr. The results of analysis were
      evaluated statistically using ANOVA one-way and three-way analysis of variance,
      variance correlation test and Spearman's test.

PMID- 22868120
TI  - Measuring parvalbumin levels in fish muscle tissue: relevance of muscle locations
      and storage conditions.
AB  - Fish is an allergenic food capable of provoking severe anaphylactic reactions.
      Parvalbumin is the major allergen identified in fish and frog muscles. Antibodies
      against fish and frog parvalbumin have been used to quantify parvalbumin levels
      from fish. However, these antibodies react variably with parvalbumin from
      different fish species. Several factors might be responsible for this variation
      including instability of parvalbumin in fish muscle as a result of frozen storage
      and differential parvalbumin expression in muscles from various locations within
      the whole fish. We aimed to investigate whether these factors contribute to the
      previously observed variable immunoreactivity of the anti-parvalbumin antibodies.
      Results showed the detection of parvalbumin by these antibodies was unaffected by
      frozen storage of muscles for 112 days. However, the parvalbumin content
      decreased in fish muscles from anterior to posterior positions. This factor may
      partially explain for the inconsistent reactivity of anti-parvalbumin antibodies
      to different fish species.

PMID- 22868121
TI  - Classification of geographical origins and prediction of delta13C and delta15N
      values of lamb meat by near infrared reflectance spectroscopy.
AB  - Near infrared spectroscopy (NIRS) combined with chemometric analysis was
      investigated for its potential to classify the geographical origin and predict
      delta(13)C and delta(15)N values of lamb meat samples (n=99) from three pastoral
      regions and two agricultural regions of China. Principal component analysis
      (PCA), discriminant partial least squares analysis (D-PLS), linear discriminant
      analysis (LDA) and partial least squares regression (PLSR) were used for data
      analysis. D-PLS and LDA correctly classified 100% of the both pastoral and
      agricultural region samples, and gave a total correct classification of 88.9% and
      75% to the five individual region samples, respectively. The best PLSR
      calibration models for predicting delta(13)C and delta(15)N of lamb meat were
      obtained with the determination coefficient (R(2)) 0.76 and 0.87, respectively.
      These results show that NIRS combined with chemometrics can be used as a rapid
      and effective method to discriminate the geographical origin and estimate the
      delta(13)C and delta(15)N of lamb meat.

PMID- 22868122
TI  - An innovative method for the preparation of mum (Thai fermented sausages) with
      acceptable technological quality and extended shelf-life.
AB  - Freshly-manufactured mum sausages were assigned to two processing methods
      (process I: stored at ~30  degrees C for 14 days; process II: stored at ~30 
      degrees C for three days, vacuum-packaged, and stored at 4  degrees C until day
      28). Physicochemical, microbial, textural, and sensory properties of samples were
      analysed. The results showed that dehydration was more intense in process I
      samples, and resulted in lower moisture content and water activity. Significant
      decreases in pH values, and increases in lactic acid were observed in both
      samples by day 3. The total microflora and lactic acid bacteria counts increased
      rapidly during the fermentation and then decreased while the Enterobacteriaceae
      counts decreased steadily. Too much dehydration resulted in tough textures and
      unacceptable sensory qualities for process I samples. In conclusion, after three
      days of fermentation, with vacuum-packaging, ripening and storage at 4  degrees C
      up to 28 days, it is possible to produce mum sausages with better qualities and
      an extended shelf life.

PMID- 22868123
TI  - Effect of ultraviolet processing on selected properties of egg white.
AB  - The effect of ultraviolet processing (10.6 and 63.7 kJ m(-2)) on selected
      properties of egg white (absorbance, particle size, protein fractions, free
      sulfhydryl content, immunoreactivity, viscosity, gelling and foaming properties)
      was investigated. Ultraviolet exposure induced the development of browning, the
      formation of large protein aggregates by disulfide exchange, and protein backbone
      cleavage. However, egg white proteins were differently sensitive to UV radiation.
      No changes in immunoreactivity, gelling temperature and gel firmness were
      observed. Independently on the UV dose, light treated egg white produced foams
      with higher stability. This effect was attributed to protein aggregates jamming
      in the fluid interstices between bubbles and/or to the higher viscosity of the
      aqueous phase. The latter was also associated to higher foam volume.

PMID- 22868124
TI  - Simultaneous quantification of major flavonoids in "Bawanghua", the edible flower
      of Hylocereus undatus using pressurised liquid extraction and high performance
      liquid chromatography.
AB  - A pressurised liquid extraction (PLE) and high performance liquid chromatography
      (HPLC) method was developed for simultaneous quantification of six major
      flavonoids in edible flower of Hylocereus undatus. In order to achieve the
      baseline separation of two pairs of isomers, the HPLC conditions were optimised
      with different kind of reversed phase columns and mobile phase gradient programs.
      In addition, the solvent concentration, extraction temperature, extraction time
      and flush cycle for PLE were also optimised. Zorbax SB-C8 (100*2.1 mm, 1.8 MUm)
      column was chosen with acetonitrile and water containing 0.1% trifluoroacetic
      acid as mobile phase, the six analytes were eluted with baseline separation. The
      calibration curves showed good linearity (r(2)>0.9994) with LODs and LOQs less
      than 0.90 and 3.60 ng respectively. The RSDs for intra- and inter-day
      repeatability was not more than 1.09% and 1.79% respectively. The overall
      recovery of the assay was 96.9-105.2%. The sample was stable for at least 12 h.
      The newly established method was successfully applied to quantify six flavonoids
      in different parts of "Bawanghua", and the commercial samples from different
      locations.

PMID- 22868125
TI  - Complex coacervation of soybean protein isolate and chitosan.
AB  - The formation of coacervates between soybean protein isolate (SPI) and chitosan
      was investigated by turbidimetric analysis and coacervate yield determination as
      a function of pH, temperature, time, ionic strength, total biopolymer
      concentration (TB(conc)) and protein to polysaccharide ratio (R(SPI/Chitosan)).
      The interaction between SPI and chitosan yielded a sponge-like coacervate phase
      and the optimum conditions for their coacervation were pH 6.0-6.5, a temperature
      of 25  degrees C, and a R(SPI/Chitosan) ratio of four independently of TB(conc).
      NaCl inhibited the complexation between the two biopolymers. Fourier transform
      infrared spectroscopy (FTIR) revealed that the coacervates were formed through
      the electrostatic interaction between the carboxyl groups of SPI (-COO(-)) and
      the amine groups of chitosan (-NH(3)(+)), however hydrogen bonding was also
      involved in the coacervation. Differential scanning calorimetry (DSC) thermograms
      indicated raised denaturation temperature and network thermal stability of SPI in
      the coacervates due to SPI-chitosan interactions. Scanning electron microscopy
      (SEM) micrographs revealed that the coacervates had a porous network structure
      interspaced by heterogeneously sized vacuoles.

PMID- 22868127
TI  - Characterisation of nucleosides and nucleobases in Mactra veneriformis by high
      performance liquid chromatography coupled with diode array detector-mass
      spectrometry (HPLC-DAD-MS).
AB  - Mactra veneriformis has been used as sea food and traditional Chinese medicine
      (TCM) for thousands of years in China. In the present study, a high performance
      liquid chromatograph coupled with photodiode array detector and electrospray
      ionisation-mass spectrometer (HPLC-DAD-ESI-MS) method was established for
      detection of the nucleosides and nucleobases in M. veneriformis from four
      aquaticultural area of Jiangsu during different harvest time of one year. The
      validated method was successfully applied to identifying 10 nucleosides and
      nucleobases in 48 M. veneriformis samples. Quantitative analysis showed that
      nucleosides and nucleobases are rich in all M. veneriformis samples. However,
      their contents vary in different areas and harvest times. Principal component
      analysis (PCA) was used to classify the 48 samples based on the contents of the
      nucleosides and nucleobases. As a result, the samples could be mainly clustered
      into four groups, which was similar as aquaticultural areas classification. Based
      on the results, present method might be applicable for the quality control of M.
      veneriformis, or even other marine shellfish aquiculture and their products, and
      the quality of M. veneriformis might be more related with aquaticultural areas.

PMID- 22868126
TI  - Protection of lung fibroblast MRC-5 cells against hydrogen peroxide-induced
      oxidative damage by 0.1-2.8 kDa antioxidative peptides isolated from whey protein
      hydrolysate.
AB  - Antioxidative peptides (0.1-2.8 kDa) obtained from gel filtration of Alcalase
      hydrolysed whey protein were subjected to individual peptide isolation by RP
      HPLC. The sub-fraction P4 and a prominent pentapeptide identified by mass
      spectrometry (Val-His-Leu-Lys-Pro) (P4c) were found to be highly antioxidative,
      therefore, used to assess the efficacy against hydrogen peroxide (H(2)O(2))
      induced human lung fibroblast MRC-5 cell oxidative injury. MRC-5 cells were
      damaged by incubation with H(2)O(2), but cell death was significantly reduced
      when exposed to P4 and P4c (P<0.05). Compared to the H(2)O(2)-damaged model
      control, P4 and P4c enhanced the activity of cell superoxide dismutase,
      glutathione peroxidase, and catalase, and decreased the levels of malonaldehyde
      (P<0.05). These results, with a more pronounced action of P4c than P4,
      demonstrated that antioxidative peptides had a significant protection of MRC-5
      cells against the toxicity caused by H(2)O(2).

PMID- 22868128
TI  - Characterisation of interactions between fish gelatin and gum arabic in aqueous
      solutions.
AB  - The interactions between fish gelatin (FG) and gum arabic (GA) in aqueous
      solutions were investigated by turbidimetry, methylene blue spectrophotometry,
      zeta potentiometry, dynamic light scattering, protein assay, and state diagram at
      40  degrees C and a total biopolymer concentration (C(T)) of 0.05%. FG underwent
      complex coacervation with GA, possibly via its conformational change, depending
      on pH and FG to GA ratio (FG:GA). The formation of FG-GA complexes was the most
      intense when pH 3.55 and FG:GA=50:50 (6.6:1 M ratio), however, the coacervate
      phase was found to be composed of a much higher FG fraction. The pH range of
      complex formation shifted to a higher pH region with increasing FG:GA. Soluble
      and insoluble FG-GA complexes were formed even in a pH region where both
      biopolymers were net-negatively charged. Varying C(T) significantly influenced
      not only the formation of FG-GA complexes but also the development and
      composition of coacervate phase.

PMID- 22868129
TI  - The neuroprotective potential of phenolic-enriched fractions from four Juniperus
      species found in Portugal.
AB  - The increase in population lifespan has enhanced the incidence of
      neurodegenerative diseases, for which there is, as yet, no cure. We aimed to
      chemically characterize phenolic-enriched fractions (PEFs) from four wild
      Juniperus sp. found in Portugal (Juniperus navicularis, Juniperus oxycedrus
      badia, Juniperus phoenicea and Juniperus turbinata) and address their potential
      as sources of natural products for treatment of neurodegenerative diseases.
      Leaves from the four Juniperus sp. evaluated contained a range of phenolic
      components which differed quantitatively between the species. The PEFs obtained
      were rich sources of phenolic compounds, exhibited acetylcholinesterase (AChE)
      inhibitory activity and also displayed effective intracellular radical scavenging
      properties in neurons submitted to oxidative injury but showed a different order
      of effectiveness compared to AChE inhibition. These properties made them good
      candidates for testing in a neurodegeneration cell model. Pre-incubation with J.
      oxycedrus badia PEF for 24h protected neurons from injury in the
      neurodegeneration cell model.

PMID- 22868130
TI  - Retardation of post-mortem changes of freshwater prawn (Macrobrachium
      rosenbergii) stored in ice by legume seed extracts.
AB  - Meat quality of freshwater prawn (Macrobrachium rosenbergii) treated with soybean
      and bambara groundnut extracts at different concentrations was monitored during
      10 days of iced storage. During storage, the control sample (without treatment)
      had a higher pH, TCA-soluble peptide content, heat soluble collagen content,
      proteolytic activities and psychrophilic bacterial count than did samples treated
      with soybean and bambara groundnut extracts. Conversely, shear force value and
      likeness scores of the control sample decreased (p<0.05), more likely associated
      with softening of muscle. The decrease in myosin heavy chain in the control
      sample was found after 6 days of storage. However, no changes in protein patterns
      of samples treated with soybean extracts at 2.5 mg/mL were found after 10 days of
      storage. Therefore, the injections of legume seed extracts, especially soybean
      extract, at a sufficient concentration, could be a means to retard muscle
      softening and maintain the qualities of freshwater prawn during iced storage.

PMID- 22868131
TI  - Efficacy of phytic acid as an inhibitor of enzymatic and non-enzymatic browning
      in apple juice.
AB  - Browning decreases the commercial value of apple juice, and therefore colour
      preservation during processing and storage is the main objective of
      manufacturers. In this study, the efficacy of phytic acid as a browning inhibitor
      for use on apple juice was investigated. Browning of apple juice treated with
      phytic acid was monitored during processing and storage. 0.1 mM Phytic acid
      inhibited the polyphenol oxidase (PPO) from the apple juice by 99.2%.
      Consequently, the apple juice treated with phytic acid had significantly lower
      browning formation during processing and after 6 months of storage at room
      temperature compared with the control (p<0.05). Results indicate that this is a
      promising way to inhibit browning in apple juice.

PMID- 22868132
TI  - Characterisation and partial purification of proteolytic enzymes from sardine by
      products to obtain concentrated hydrolysates.
AB  - A procedure to recover proteases and lipases from the by-products of Monterey
      sardine (Sardinops sagax caerulea) has been developed, comprising 2 steps: a
      centrifugation at low temperature to eliminate more than 90% of the initial fat
      content, and an acetone precipitation step. After this treatment, enzymatic
      activity increased by 33.8% for lipase, 15.5% for trypsin, 14.8% for
      chymotrypsin, 93.4% for aminopeptidase, and 19.7% for pepsin. The extents of
      hydrolysis of fish by-product proteins by endogenous enzyme by-product extract,
      viscera concentrate extract, and commercial Alcalase(r) were 62%, 85%, and 28%,
      respectively. The two extract preparations from sardine by-product (viscera and
      by-product concentrate extracts) produced 3-fold greater hydrolysis than with the
      commercial enzyme. The recovery of enzyme concentrates from sardine waste has
      both ecological and economical advantages for the fish industry.

PMID- 22868133
TI  - Rapid measurement of total acid content (TAC) in vinegar using near infrared
      spectroscopy based on efficient variables selection algorithm and nonlinear
      regression tools.
AB  - Total acid content (TAC) is an important index in assessing vinegar quality. This
      work attempted to determine TAC in vinegar using near infrared spectroscopy. We
      systematically studied variable selection and nonlinear regression in calibrating
      regression models. First, the efficient spectra intervals were selected by
      synergy interval PLS (Si-PLS); then, two nonlinear regression tools, which were
      extreme learning machine (ELM) and back propagation artificial neural network (BP
      ANN), were attempted. Experiments showed that the model based on ELM and Si-PLS
      (Si-ELM) was superior to others, and the optimum results were achieved as
      follows: the root mean square error of prediction (RMSEP) was 0.2486 g/100mL, and
      the correlation coefficient (R(p)) was 0.9712 in the prediction set. This work
      demonstrated that the TAC in vinegar could be rapidly measured by NIR
      spectroscopy and Si-ELM algorithm showed its superiority in model calibration.

PMID- 22868134
TI  - Suillus collinitus methanolic extract increases p53 expression and causes cell
      cycle arrest and apoptosis in a breast cancer cell line.
AB  - In the present work, methanolic, ethanolic and boiled water extracts of Suillus
      collinitus were chemically characterised and submitted to an evaluation of their
      bioactive properties (antioxidant potential and cytotoxic activity in tumor cell
      lines). Phenolic acids and sugars were identified chromatographically and
      quantified in the methanolic and boiled water extracts, respectively. S.
      collinitus ethanolic extract had the highest antioxidant activity. Nevertheless,
      with respect to cell growth inhibition, the methanolic extract was the most
      potent extract, particularly in MCF-7 cells (GI(50) 25.2+/-0.2 MUg/ml). Moreover,
      the GI(50) concentration of this extract induced a G1 cell cycle arrest, with a
      concomitant decrease in the percentage of cells in the S phase. Furthermore, it
      caused an increase in the percentage of apoptotic cells, from 6.0+/-0.2% in
      untreated cells, to 15.3+/-2.0% in cells treated with the GI(50) concentration
      and to 16.3+/-2.0% in cells treated with 2*GI(50) concentration. In addition, 48
      h treatment with the GI(50) concentration caused a strong increase in the levels
      of p53, p21, and cleaved PARP, together with a decrease in Bcl-2 and XIAP.
      Results indicate that S. collinitus may be a promising source of bioactive
      compounds. Particularly, its methanolic extract appears to have a p53-mediated
      effect on the normal cell cycle distribution and apoptosis induction in a human
      breast tumor cell line.

PMID- 22868135
TI  - Quantitative determination of fatty acid compositions in micro-encapsulated fish
      oil supplements using Fourier transform infrared (FTIR) spectroscopy.
AB  - The research describes a rapid method for the determination of fatty acid (FA)
      contents in a micro-encapsulated fish-oil (MUEFO) supplement by using attenuated
      total reflection Fourier transform infrared (ATR-FTIR) spectroscopic technique
      and partial least square regression (PLSR) analysis. Using the ATR-FTIR
      technique, the MUEFO powder samples can be directly analysed without any pre
      treatment required, and our developed PLSR strategic approach based on the
      acquired spectral data led to production of a good linear calibration with
      R(2)=0.99. In addition, the subsequent predictions acquired from an independent
      validation set for the target FA compositions (i.e., total oil, total omega-3
      fatty acids, EPA and DHA) were highly accurate when compared to the actual values
      obtained from standard GC-based technique, with plots between predicted versus
      actual values resulting in excellent linear fitting (R(2)>=0.96) in all cases.
      The study therefore demonstrated not only the substantial advantage of the ATR
      FTIR technique in terms of rapidness and cost effectiveness, but also its
      potential application as a rapid, potentially automated, online monitoring
      technique for the routine analysis of FA composition in industrial processes when
      used together with the multivariate data analysis modelling.

PMID- 22868136
TI  - Analysis of free and esterified sterols in edible oils by online reversed phase
      liquid chromatography-gas chromatography (RPLC-GC) using the through oven
      transfer adsorption desorption (TOTAD) interface.
AB  - An online reversed phase liquid chromatography-gas chromatography (RPLC-GC)
      method is proposed to quantify free, total and esterified sterols of edible oils.
      To determine free sterols the diluted oils are injected into the liquid
      chromatograph, where free sterols are separated from triglycerides and the sterol
      fraction is automatically transferred to the gas chromatograph to be analysed. To
      determine total sterols the samples were saponified with potassium hydroxide in
      ethanolic solution and the unsaponifiable fraction was extracted with diethyl
      ether. The extract was then analysed by RPLC-GC, avoiding the laborious thin
      layer chromatography step used in the Official European Union (EU) Method. The
      relative standard deviations (RSDs) from the absolute peak area varied from 7.6%
      to 15.8%. Limits of detection (LODs) were less than 8.5 mg/kg. No variability in
      retention time was observed. The method was applied to the determination of total
      sterols in edible oil samples and the results were compared with those obtained
      with the Official EU Method. Good agreement was found between both methods,
      except in the case of campesterol.

PMID- 22868137
TI  - Profile and distribution of soluble and insoluble phenolics in Chinese rapeseed
      (Brassica napus).
AB  - The profile and distribution of soluble and insoluble phenolics in 10 rapeseed
      (Brassica napus) varieties were studied in this work. Photometric results show
      that the soluble total phenolic content (TPC) and the total tannin content (TTC)
      of rapeseed dehulled flours are much higher than those of rapeseed hulls. Soluble
      and insoluble phenolics were further analysed by HPLC/MS and MS/MS. For soluble
      phenolics, seven species were identified and quantified. Sinapine was found to be
      the major component in both defatted rapeseed hulls and dehulled flours, with its
      content ranging from 0.93 to 1.76 mg/g and 15.65 to 21.88 mg/g, respectively. For
      insoluble phenolics, eight phenolic acids were detected in rapeseed hulls, while
      only two of them were found in their dehulled flours. Sinapic acid and
      protocatechuic acid, which also were found in dehulled flours, were identified as
      two major insoluble phenolics in rapeseed hulls. Insoluble TPCs in defatted
      rapeseed hulls and dehulled flours were shown to be in the similar range.

PMID- 22868138
TI  - Use of a continuous leaching method to assess the oral bioaccessibility of trace
      elements in seafood.
AB  - A continuous leaching method, coupled online with inductively coupled plasma mass
      spectrometry (ICP-MS) was used on seafood samples to assess the maximum
      bioaccessibility of several trace elements. The method indeed involves continuous
      leaching of the food sample by artificial saliva and gastric juice, successively,
      where this exposition of the food to fresh reagent drives the dissolution
      equilibrium to the right. Leaching with intestinal juice had to be omitted
      because it resulted in clogging problems. The experimental apparatus includes a
      mini-column of powdered sample, which is directly connected to the nebulizer of
      an ICP-MS instrument. The on-line approach allows a quick assessment of the
      maximum bioaccessibility of elements of interest by monitoring the real-time
      release of elements by a given reagent. The method was applied to determine the
      bioaccessibility of four toxic elements (Al, Cd, Hg, and Pb) and of four
      essential elements (V, Mn, Cu, and Zn) in certified reference materials and in
      actual seafood samples. In all cases, mass balance was verified by carrying out
      the total digestion of the remaining residue from the mini-column and the
      relationship between total concentration and bioaccessibility was examined.

PMID- 22868139
TI  - Curcuma longa and Curcuma mangga leaves exhibit functional food property.
AB  - Although leaves of Curcuma mangga and Curcuma longa are used in food
      preparations, the bioactive components in it are not known. In this study,
      antioxidant, antiinflammatory and anticancer activities of leave extracts and its
      isolates were investigated using established bioassay procedures in our
      laboratory. The leaf extracts of both plants gave similar bioassay and
      chromatographic profiles. The methanolic and water extracts of C. mangga (CMM and
      CMW) and C. longa (CLM and CLW), at 100 MUg/mL, inhibited lipid peroxidation
      (LPO) by 78%, 63%, 81% and 43%, cyclooxygenase enzymes COX-1 by 55%, 33%, 43% and
      24% and COX-2 by 65%, 55%, 77% and 69%, respectively. At same concentration, CMM,
      CMW, CLM and CLW showed growth inhibition of human tumour cell lines by 0-46%.
      Therefore, a bioassay-guided isolation of water and methanolic extracts of C.
      longa was carried out and afforded nine isolates. At 25 MUg/mL, these compounds
      inhibited LPO by 11-87%, COX-1 and -2 enzymes by 0-35% and 0-82% and growth of
      human tumour cells by 0-36%, respectively.

PMID- 22868140
TI  - Effect of gamma and electron beam irradiation on the physico-chemical and
      nutritional properties of mushrooms: a review.
AB  - The short shelf-life of mushrooms is an obstacle to the distribution and
      marketing of the fresh product. Thus, prolonging postharvest storage, while
      preserving their quality, would benefit the mushroom industry as well as
      consumers. There has been extensive research on finding the most appropriate
      technology for mushrooms preservation. Gamma, electron-beam and UV irradiation
      have been shown to be potential tools in extending the postharvest shelf-life of
      fresh mushrooms. Studies evaluating the effects of ionizing radiation are
      available mainly in cultivated species such as Agaricus bisporus, Lentinus edodes
      and Pleurotus ostreatus. This review comprises a comprehensive study of the
      effects of irradiation on physico-chemical parameters (weight, colour, texture
      and pH), chemical compounds including nutrients (proteins, sugars and vitamins)
      and non-nutrients (phenolics, flavonoids and flavour compounds), and on
      biochemical parameters such as enzymatic activity of mushrooms for different
      species and from different regions of the world.

PMID- 22868141
TI  - Interaction of phenolic compounds with bovine serum albumin (BSA) and alpha
      amylase and their relationship to astringency perception.
AB  - The ability of grape seed extracts to bind to bovine serum albumin (BSA) and
      alpha-amylase was studied by fluorescence quenching of protein intrinsic
      fluorescence and nephelometry. The influence of grape seed ripeness on
      astringency was also evaluated. From the spectra obtained, the modified Sterm
      Volmer (K(app)) and the bimolecular quenching constants were calculated. Results
      showed that grape seed extracts had good affinity for proteins. The association
      strength of tannin-protein interactions varied with changes in tannin structure
      associated with the degree of ripeness affecting the binding/quenching process.
      In all cases studied, higher values of K(app) were obtained in samples at harvest
      which have greater ability to bind to proteins than have samples at post-veraison
      time. Nephelometric assays show the same trend as do fluorescence quenching
      studies. A possible explanation for this is that, as seeds ripen, their tannins
      increase in molecular mass, which relates to an increase in hydrophobicity of the
      molecules, and this increases protein affinity. However, that is contrary to the
      reported decrease in astringency of grape seeds during maturity. This indicates
      that tannin-protein interactions are not the only explanation for the complex
      sensations of astringency of grape seeds.

PMID- 22868142
TI  - The effects of soy on freezable bread dough: a magnetic resonance study.
AB  - Hygroscopic soy ingredients were hypothesised to slow the rate of water migration
      in unleavened bread dough during frozen storage. Thawed soy (18% dry weight) and
      wheat dough samples were assessed using non-destructive nuclear magnetic
      resonance (NMR) and magnetic resonance imaging (MRI) for up to 8 wks frozen
      storage time. MRI suggested a spatially homogeneous, net increase in proton
      mobility with frozen storage and, with solution state proton NMR, distinct "free"
      and "bound" states were discerned. T(2) relaxation times of the majority proton
      population suggested increased mobility with frozen storage time, and statistical
      difference from the fresh sample was seen later for the soy samples than the
      wheat samples. As seen by (13)C-solid state NMR, the crystallinity of the starch
      was not affected by either soy addition or frozen storage. In conclusion,
      addition of soy to bakery products led to slightly enhanced preservation of
      "fresh" characteristics of the dough during frozen storage.

PMID- 22868143
TI  - Identification of isomers and determination of octenylsuccinate in modified
      starch by HPLC and mass spectrometry.
AB  - A high performance liquid chromatographic (HPLC) analysis of octenylsuccinic
      anhydride (OSA) reagent and its bound and un-reacted forms in modified starch was
      developed. The HPLC system consisted of a C(18) column, an elution system of
      acetonitrile and water containing 0.1% TFA (45:55, v/v), and a diode array
      detector (DAD). Using the combination of HPLC-DAD and HPLC-APCI (atmospheric
      pressure chemical ionisation)-MS (mass spectrometry), four main and two minor
      peaks were identified as 1-OS acid, cis-2-OS acid, trans-2-OS acid, 1-OSA, cis-2
      OSA and trans-2-OSA, respectively. Both free and bound OS content in modified
      starch were successfully determined by HPLC, and direct measurement of
      composition of OS was achieved.

PMID- 22868144
TI  - Green tea extract: possible mechanism and antibacterial activity on skin
      pathogens.
AB  - Camellia sinensis (tea) is known for its therapeutic properties (anti
      inflammatory, anti-microbial, anti-tumour, anti-oxidative and anti-ageing).
      Although, anti-microbial properties of green tea have been studied, its role
      against bacterial strains related to skin infections and mechanism of action is
      not well understood. We focussed on exploring anti-microbial activity and the
      basic mechanism of aqueous green tea leaf extract on selected bacterial strains.
      Staphylococcus epidermidis, Micrococcus luteus, Brevibacterium linens,
      Pseudomonas fluorescens and Bacillus subtilis were found to be sensitive to green
      tea extract via disc diffusion assay (zone of inhibition >=7 mm). Minimal
      inhibitory concentration (MIC) was determined via nitro blue tetrazolium (NBT)
      assay (0.156-0.313 mg/ml). Moreover, the aqueous extract was found to be not
      toxic to the Vero cell-line up to a concentration of 500 MUg/ml. The effect of
      aqueous extract on adhesion of different bacteria to Vero cells indicated that it
      inhibits the adhesion at its MIC value.

PMID- 22868145
TI  - Simultaneous determination of 15 aminoglycoside(s) residues in animal derived
      foods by automated solid-phase extraction and liquid chromatography-tandem mass
      spectrometry.
AB  - An automated method has been developed for the simultaneous quantification of 15
      aminoglycosides in muscle, liver (pigs, chicken and cattle), kidney (pigs and
      cattle), cow milk, and hen eggs by liquid chromatography tandem mass
      spectrometry. Homogenized samples were extracted by monopotassium phosphate
      buffer (including ethylene diamine tetraacetic acid), and cleaned up with auto
      solid-phase extraction by carboxylic acid cartridges. The analytes were separated
      by a specialized column for aminoglycosides, and eluted with trifluoroacetic acid
      and acetonitrile. The decision limits (CCalpha) of apramycin, gentamycin,
      tobramycin, paromomycin, hygromycin, neomycin, kanamycin, sisomicin, netilmicin,
      ribostamycin, kasugamycin, amikacin, streptomycin, dihydrostreptomycin and
      spectinomycin were ranged from 8.1 to 11.8 MUg/kg and detection capabilities
      (CCbeta) from 16.4 to 21.8 MUg/kg. High correlation coefficients (r(2)>0.99) of
      calibration curves for the analytes were obtained within linear from 20 to 1000
      MUg/kg. Reasonable recoveries (71-108%) were demonstrated with excellent relative
      standard deviation (RSD). This method is simple pretreatment, rapid determination
      and high sensitivity, which can be used in the determination of multi
      aminoglycosides in complex samples.

PMID- 22868146
TI  - Traceability of Italian garlic (Allium sativum L.) by means of HRMAS-NMR
      spectroscopy and multivariate data analysis.
AB  - (1)H High Resolution Magic Angle Spinning-Nuclear Magnetic Resonance (HRMAS-NMR)
      spectroscopy was used to analyse garlic (Allium sativum L.) belonging to red and
      white varieties and collected in different Italian regions, in order to address
      the traceability issue. 1D and 2D NMR spectra, performed directly on untreated
      small pieces of garlic, so without any sample manipulation, allowed the
      assignment of several compounds: organic acids, sugars, fatty acids, amino acids
      and the nutritionally important fructo-oligosaccharides and allyl-organosulphur
      compounds. Application of Partial Least Squares projections to latent structures
      Discrimination Analysis provided an excellent model for the discrimination of
      both the variety and, most important, the place origin, allowing the
      identification of the metabolites contributing to such classifications. The
      presence of organosulphurs, allicin and some allyl-organosulphurs found by HRMAS
      NMR, was confirmed also by SPME-GC-MS; 11 molecules were identified, containing
      from one up to three sulphur atoms and with and without allyl moieties.

PMID- 22868147
TI  - Effect of harvest date on the nutritional quality and antioxidant capacity in
      'Hass' avocado during storage.
AB  - The effect of harvest date on nutritional compounds and antioxidant activity
      (AOC) in avocado (Persea americana Mill. cv Hass) fruit during storage was
      determined. The fruits were harvested at seven different dates and ripened at 25 
      degrees C following 21 or 35 days of cold storage. The results indicated that the
      phenolic and glutathione contents were increased and the ascorbic acid content
      was not significantly different in early harvested fruit (January to March), and
      the phenolic, ascorbic acid and glutathione contents were increased slightly and
      then decreased on late harvested fruit (April to June). Similar trends were
      observed in the changes of AOC. Furthermore, AOC in early harvested fruit after
      storage for 35 days was much higher than that in late harvested fruit after
      storage for 21 days. Therefore, avocado can be harvested earlier for economic
      benefits according to the market and can keep high nutritional value for human
      health benefits.

PMID- 22868148
TI  - Sodium alginate as feed additive in cultured sea bream (Sparus aurata): does it
      modify the quality of the flesh?
AB  - The objective of this study was to evaluate the effect of sodium alginate
      obtained from brown seaweed as a prebiotic supplement to the feed of reared sea
      bream (Sparus aurata). Addition of the alginate to a control diet was
      investigated at both concentrations 2% and 5%. Proximate composition in the flesh
      were not modified significantly by sodium alginate inclusion in the diet of the
      sea bream; however the fat and ash content in the specimens supplemented with 5%
      alginate were found to be significantly higher than those found in individuals
      who were fed the control diet. No significant differences in mineral content,
      fatty acid profiles, cholesterol content, texture parameters and sensory
      acceptability among the three studied groups. Results obtained in this study
      offer support for the use of alginate as a feed additive in sea bream diets since
      no significant effects were found in the flesh quality and characteristics of
      commercial size sea bream.

PMID- 22868149
TI  - Sterols heating: degradation and formation of their ring-structure polar
      oxidation products.
AB  - Cholesterol and phytosterols can be oxidised under heating conditions to give
      sterol oxidation products (SOPs), known by their toxic effects. This paper
      studied the degradation of cholesterol and three plant sterols during a 360 min
      heating treatment (180  degrees C). The formation and further degradation of SOPs
      was also analysed by GC-MS. Results revealed a sterol susceptibility to
      degradation according to the following decreasing order: campesterol~beta
      sitosterol>=stigmasterol>cholesterol. The degradation curve fit (R(2)=0.907
      0.979) a logarithmic model. SOPs increased their concentration during the first 5
      10 min and thereafter, their degradation rate was higher than their formation
      rate, resulting in a decrease over time. Irrespective of the sterol from which
      they had derived, 7-keto derivatives presented the highest levels throughout the
      entire process, and also SOPs with the same type of oxidation followed a similar
      degradation pattern (R=0.90-0.99).

PMID- 22868150
TI  - Characterisation of three starch degrading enzymes: thermostable beta-amylase,
      maltotetraogenic and maltogenic alpha-amylases.
AB  - Maltogenic alpha-amylase from Bacillus stearothermophilus (BStA) is widely used
      as bread crumb anti-firming enzyme. A maltotetraose-forming alpha-amylase from
      Pseudomonas saccharophila (PSA) was recently proposed as alternative, hence the
      need to compare both exo-acting enzymes with some endo-action component. A purely
      exo-acting thermostable beta-amylase from Clostridium thermosulfurogenes (CTB)
      was included for reference purposes. Under the experimental conditions used,
      temperature optima of the enzymes are rather similar (60-65  degrees C), but
      temperature stability decreased in the order BStA, PSA and CTB. The action of the
      enzymes on different substrates and their impact on the rheological behaviour of
      maize starch suspensions demonstrated that, while CTB acts exclusively through an
      exo-action mechanism, BStA displayed limited endo-action which became more
      pronounced at higher temperatures. PSA has more substantial endo-action than
      BStA, which is rather temperature independent. This is important for their impact
      in processes such as breadmaking, where temperature is gradually increased.

PMID- 22868151
TI  - Improving the determination of moisture in edible oils by FTIR spectroscopy using
      acetonitrile extraction.
AB  - A Fourier transform infrared (FTIR) method developed for the analysis of moisture
      in edible oils using dry acetonitrile as the extraction solvent was re-examined
      with the objective of improving its overall sensitivity and reproducibility.
      Quantitation was based on the H-O-H bending absorption at ~1630 cm(-1) instead of
      the bands in the OH stretching region, fewer interferences being an issue in the
      former as opposed to the latter region. In addition, a spectroscopic dilution
      correction procedure was developed to compensate for any miscibility of oil
      samples with acetonitrile, and gap-segment 2nd derivative spectra were employed
      to minimise the associated possibility of spectral interferences from absorptions
      of the oils. In comprehensive standard addition experiments using a variety of
      edible oils, the FTIR method was shown to recover the amounts of water
      quantitatively added to dry oil with an accuracy of +/-20 ppm when the spectra of
      the acetonitrile extracts of the water-spiked oils were ratioed against the
      spectra of the acetonitrile extracts of the corresponding dry oils. The accuracy
      deteriorated substantially when the spectra of the acetonitrile extracts of the
      water-spiked oils were ratioed against the spectrum of the acetonitrile
      extraction solvent only. However, the primary variable affecting the apparent
      difference in the accuracy of the two approaches was determined to be the
      variability in the residual moisture content of the dried oils used in the
      standard addition experiments, as confirmed by an FTIR procedure based on H-D
      exchange with D(2)O. The FTIR method as structured is amenable to automation
      (>120 samples/h) and provides a very competitive means by which to routinely
      measure moisture present in a variety of hydrophobic materials that are normally
      the domain of Karl Fischer titration, such as edible oils, mineral oils,
      biodiesel and fuels.

PMID- 22868152
TI  - Structural characteristics of water-soluble polysaccharides from Rabdosia serra
      (MAXIM.) HARA leaf and stem and their antioxidant capacities.
AB  - Water-soluble polysaccharides of Rabdosia serra leaf and stem were fractionated
      by ultrafiltration and DEAE-Sepharose fast flow chromatogram to obtain water
      (RSLP-I and RSSP-I), 0.1M NaCl (RSLP-II and RSSP-II) and 0.2M NaCl (RSLP-III and
      RSSP-III) eluates. Their molecular weights were determined by high performance
      gel permeation chromatography. Monosaccharide composition analysis indicated that
      the water eluates comprised of rhamnose, arabinose, xylose, mannose, glucose and
      galactose. The ascending percentage of galactose and descending percentage of
      glucose in the eluates were observed with the increase of NaCl concentration. The
      branched RSLP-I and RSSP-I were composed mainly of ->6)-Glcp-(1->, ->6)-Galp-(1
      >, and ->5)-Araf-(1-> residues with the ratio of 15.0:4.2:3.8 and 5.5:6.4:3.5,
      respectively. However, a low level of 1,6-linked glucosyl was observed in RSLP
      II, RSSP-II, RSLP-III and RSSP-III. The structural characteristics were further
      analysed by infrared spectrophotometry. The purified leaf and stem
      polysaccharides possessed moderate antioxidant capacities.

PMID- 22868154
TI  - Fast determination of bioactive compounds from Lycopersicon esculentum Mill.
      leaves.
AB  - Lycopersicon esculentum leaves, usually considered as a by-product of tomato
      production, present several bioactive compounds of interest for industries like
      food, pharmaceutical and cosmetics. Nevertheless, before industrial application,
      suitable methods to identify and quantify those metabolites should be developed.
      In this study agitation with aqueous methanol was used for phenolic compounds
      extraction. Solid-phase extraction (SPE) was performed as the purification step
      before alkaloids analysis. Among the SPE sorbents tested, sulphonic acid bonded
      silica with H(+) counterion (SCX) proved to be the most efficient one for
      removing interfering components. Fifteen phenolics and four steroidic alkaloids
      were identified in 35 and 20 min analysis, respectively. The optimised methods
      were validated, revealing to be accurate, fast, simple and sensitive. Thus, these
      methods represent an easy and fast analytical approach, using equipment available
      in almost laboratory, which render them to be appropriate for routine analysis.

PMID- 22868153
TI  - Susceptibility of anthocyanins to ex vivo degradation in human saliva.
AB  - Some fruits and their anthocyanin-rich extracts have been reported to exhibit
      chemopreventive activity in the oral cavity. Insights regarding oral metabolism
      of anthocyanins remain limited. Anthocyanin-rich extracts from blueberry,
      chokeberry, black raspberry, red grape, and strawberry were incubated ex vivo
      with human saliva from 14 healthy subjects. All anthocyanins were partially
      degraded in saliva. Degradation of chokeberry anthocyanins in saliva was
      temperature dependent and decreased by heating saliva to 80  degrees C and after
      removal of cells. Glycosides of delphinidin and petunidin were more susceptible
      to degradation than those of cyanidin, pelargonidin, peonidin and malvidin in
      both intact and artificial saliva. Stability of di- and tri-saccharide conjugates
      of anthocyanidins slightly, but significantly, exceeded that of monosaccharide
      compounds. Ex vivo degradation of anthocyanins in saliva was significantly
      decreased after oral rinsing with antibacterial chlorhexidine. These results
      suggest that anthocyanin degradation in the mouth is structure-dependent and
      largely mediated by oral microbiota.

PMID- 22868155
TI  - Phytochemical investigations and biological potential screening with cellular and
      non-cellular models of globe amaranth (Gomphrena globosaL.) inflorescences.
AB  - Gomphrena globosaL. is a popular edible plant used as food colourant and in
      traditional medicine. In this work, 24 phenolic compounds and eight betacyanins
      were determined by HPLC-DAD in three different extracts of G. globosa
      inflorescences. The decoction presented the highest amount of phenolic compounds,
      kaempferol-3-O-(6-rhamnosyl)hexoside plus kaempferol-3-O-hexoside being the main
      compounds. The rich betacyanins extract showed isogomphrenin III and gomphrenin
      III as major metabolites. Decreases in the nitric oxide amounts were observed in
      LPS-stimulated RAW 264.7 cells. In vitro scavenging micro assays against several
      reactive species revealed a great antioxidant capacity, particularly against
      superoxide radical. In general, the best results were obtained with decoction.
      Some relationships between activity and composition were established. The data
      provide evidence of the G. globosa inflorescences potential as a source of anti
      inflammatory compounds, with relevance for the treatment of acute or chronic
      inflammatory conditions, and health-promoting antioxidants for use by both food
      and pharmaceutical industries.

PMID- 22868156
TI  - Isolation of some luteolin derivatives from Mentha longifolia (L.) Hudson subsp.
      longifolia and determination of their genotoxic potencies.
AB  - This study was designed to evaluate the mutagenic and antimutagenic activities of
      luteolin derivatives (luteolin 7-O-glucoside, luteolin 7-O-rutinoside and
      luteolin 7-O-glucuronide) isolated from Mentha longifolia (L.) Huds. subsp.
      longifolia by using Ames Salmonella test (TA 1535 and TA1537 strains). In the
      antimutagenicity assays, luteolin 7-O-glucoside, luteolin 7-O-rutinoside and
      luteolin 7-O-glucuronide showed antimutagenic effects on TA1537 and TA1535
      strains. The highest inhibition rates for luteolin 7-O-glucoside, luteolin 7-O
      rutinoside and luteolin 7-O-glucuronide on TA1537 strain were 84.03%, 87.63% and
      67.77%, respectively. Similarly, in the antimutagenicity assays performed with
      the TA1535 strain, the inhibition rates for luteolin 7-O-glucoside and luteolin 7
      O-rutinoside were 23.86% and 23.76% respectively. Our findings showed that the
      antimutagenic properties of luteolin derivatives on TA1537 and TA1535 strains
      have been found to be structure dependent. The clarification of differences in
      antimutagenic potency of these luteolin derivatives based on their structures has
      been demonstrated in this study.

PMID- 22868157
TI  - Zinc incorporation capacity of whey protein nanoparticles prepared with
      desolvation with ethanol.
AB  - Whey protein isolate (WPI) nanoparticles were prepared using ethanol desolvation,
      and their capacity to incorporate ZnCl(2) was analysed. Desolvation was carried
      out at pH 9 and the volume of added ethanol was 0-3 times the volume of protein
      solution. The desolvated solutions were dispersed in acidified water (pH 3)
      immediately after desolvation. The size of the WPI nanoparticles increased with
      the volume ratio of ethanol:water used, as well as with the amount of ZnCl(2).
      The nanoparticles showed high incorporation efficiencies, and remained stable
      after 30 days of storage at 22  degrees C. The amount of zinc incorporated in the
      WPI particle suspensions was within the range of daily zinc requirements for
      healthy adults.

PMID- 22868158
TI  - Convenient solid phase extraction of cephalosporins in milk using a molecularly
      imprinted polymer.
AB  - In this paper, a molecularly imprinted polymer (MIP) for cephalosporin molecules
      (cephalexin (CFL) and cephapirin (CFP)), was prepared by non covalent molecular
      imprinting approach and applied to solid phase extraction (SPE). For MIP
      synthesis, a tributylammonium cefadroxil salt (TBA-CFD) was used as template with
      methacrylic acid and ethylene glycol dimethacrylate as monomer and cross-linker,
      respectively, in acetone-methanol 92/8 (v/v) mixture. The selectivity of MIP
      versus non imprinted polymer (NIP) was confirmed for CFL, CFD and CFP in standard
      solutions as well as in milk samples. The efficiency of the synthesized MIP was
      evaluated by means of the application of the proposed MIP-SPE procedure to spiked
      milk samples previous to the HPLC method for the detection of cephalosporins. The
      MIP-SPE recoveries were higher than 60% for the three target analytes in spiked
      milk.

PMID- 22868160
TI  - Exposure of grapes to smoke of vegetation with varying lignin composition and
      accretion of lignin derived putative smoke taint compounds in wine.
AB  - Smoke taint in wines from bushfire smoke exposure has become a concern for wine
      producers. Smoke taint compounds are primarily derived from pyrolysis of the
      lignin component of fuels. This work examined the influence of the lignin
      composition of pyrolysed vegetation on the types of putative smoke taint
      compounds that accrue in wines. At veraison, Merlot vines were exposed to smoke
      generated from five vegetation types with differing lignin composition. Smoke was
      generated under pyrolysis conditions that simulated bushfire temperature
      profiles. Lignin and smoke composition of each fuel type along with putative
      smoke taint compounds in wines were determined. The results showed that,
      regardless of fuel type, the commonly reported guaiacyl lignin derived smoke
      taint compounds, guaiacol and 4-methylguaiacol, represented about 20% of the
      total phenols in wines. Quantitatively, syringyl lignin derived compounds
      dominated the total phenol pools in both free and bound forms. The contributions
      of p-hydroxyphenyls were generally similar to the guaiacyl sources. A further
      unexpected outcome of the study was that pine smoke affected wines had
      significantly elevated levels of syringols compared to the controls although pine
      fuel and its smoke emission lacked syringyl products.

PMID- 22868159
TI  - Determination of fungicide residues in baby food by liquid chromatography-ion
      trap tandem mass spectrometry.
AB  - Current European Commission Directives on foods for infants and young children
      places emphasis on the control of pesticide residues at levels below 10 MUg kg(
      1). In the present work, a liquid chromatography electrospray ionisation ion trap
      tandem mass spectrometry (LC-Ion Trap-MS/MS) has been developed for the
      multiresidue of 10 multiclass fungicides (carbendazim, thiabendazole, imazalil,
      tridemorph, triadimefon, bitertanol, prochloraz, flutriafol, myclobutanil and
      diphenylamine) in fruit-based baby food. The developed method is based on a
      simple sample treatment (QuEChERS), which consists of a liquid-liquid extraction
      using acetonitrile, followed by a clean-up step based on dispersive solid-phase
      extraction with primary secondary amine (PSA). Subsequent identification and
      quantitation was accomplished by liquid chromatography/electrospray tandem mass
      spectrometry using an ion-trap mass spectrometer in the product ion scan MS/MS
      mode. Matrix effects were evaluated in LC-MS and LC-MS/MS mode experiments,
      obtaining a reduction of these effects when working in MS/MS mode for most of the
      analytes. Limits of detection (LOD) were between 0.5 and 3.0 MUg kg(-1) depending
      on the pesticide studied, all being within European Union regulations for baby
      food. Finally, the proposed method was applied to 25 baby food samples obtained
      from local supermarkets. Imazalil, thiabendazole and carbendazim were detected in
      the studied samples. However, none of the samples tested were found to be upper
      the EU standard.

PMID- 22868161
TI  - The effects of physical refining on the formation of 3-monochloropropane-1,2-diol
      esters in relation to palm oil minor components.
AB  - The formation of 3-monochloropropane-1,2-diol (3-MCPD) esters in refined palm oil
      during deodorisation is attributed to the intrinsic composition of crude palm
      oil. Utilising D-optimal design, the effects of the degumming and bleaching
      processes on the reduction in 3-MCPD ester formation in refined palm oil from
      poor-quality crude palm oil were studied relative to the palm oil minor
      components that are likely to be their precursors. Water degumming remarkably
      reduced 3-MCPD ester formation by up to 84%, from 9.79 mg/kg to 1.55 mg/kg.
      Bleaching with synthetic magnesium silicate caused a further 10% reduction, to
      0.487 mg/kg. The reduction in 3-MCPD ester formation could be due to the removal
      of related precursors prior to the deodorisation step. The phosphorus content of
      bleached palm oil showed a significant correlation with 3-MCPD ester formation.

PMID- 22868162
TI  - Effect of the red seaweed Mastocarpus stellatus intake on lipid metabolism and
      antioxidant status in healthy Wistar rats.
AB  - Health-promoting effect of dietary supplementation with the red seaweed
      Mastocarpus stellatus was studied. Its major component is dietary fibre (31.7/100
      g dry weight), 72% as soluble fibre, mainly formed by carrageenans, sulphated
      galactans of red seaweeds. Thus, rats were fed either a basal- or an algal
      supplemented diet (10%). Then, lipid metabolism was assessed in serum, and
      reducing power measured in serum and caecum by FRAP method. Also, caecal pH was
      monitored and short chain fatty acids analysed by gas-liquid chromatography.
      Seaweed intake reduced significantly triglycerides and total cholesterol in
      healthy rats, but not atherogenic index. Also, a significant increase in caecal
      moisture and proportion of acetic and propionic acids was obtained but no clear
      prebiotic effect was shown. Sulphated-galactans seemed to be related to the
      antioxidant status improvement in caecum and also to the 1.7-fold increase in
      anticoagulant capacity of plasma. Therefore, Mastocarpus could be regarded as a
      source of functional ingredients but its health benefits need to be further
      explored depending on specific use.

PMID- 22868163
TI  - On the bioavailability of flavanols and anthocyanins: flavanol-anthocyanin
      dimers.
AB  - The bioavailability of flavanols, anthocyanins and anthocyanin-derived pigments
      like flavanol-anthocyanin dimers already reported to occur in food products is a
      major unsolved issue. The absorption of the flavanol-anthocyanin dimer (+)
      catechin-(4,8)-malvidin-3-O-glucoside (Cat-Mv3glc) through Caco-2 cells was
      assessed by performing transepithelial transport assays. The ability of Cat
      Mv3glc to cross Caco-2 cells was compared with that of malvidin-3-glucoside
      (Mv3glc), (+)-catechin (Cat) and procyanidin B3 (Cat-Cat), in order to evaluate
      the influence of some structural features on the transport efficiency. The
      flavanol-anthocyanin dimer was absorbed in this intestinal model although with a
      lower efficiency than the monomers Cat and Mv3glc. On the other hand, Cat-Mv3glc
      was found to cross the intestinal barrier model more significantly than Cat-Cat.
      This feature may be related to the presence of the glucose moiety in its
      structure. Overall, this study brings more insights into the bioavailability of
      anthocyanins and flavanols and represents the first report on the bioavailability
      of flavanol-anthocyanins.

PMID- 22868164
TI  - Crystal structure of a major seed storage protein, 11S proglobulin, from
      Amaranthus hypochondriacus: insight into its physico-chemical properties.
AB  - Amaranth is a crop known for its high quality proteins. 11S Globulin is one of
      the most abundant and important storage proteins of the amaranth grain. Here, we
      report the crystal structure of amaranth 11S proglobulin at a final resolution of
      2.28 A. It belonged to the space group P6(3) with cell dimensions a=b=96.6,
      c=75.0 A. It contains one asymmetric unit consisting of 372 residues and 100
      water molecules. Disordered regions in the model approximately correspond to the
      variable regions of the 11S globulins. The structure has an extended alpha-helix
      and beta-barrel domains at both N-terminal and C-terminal regions, which are
      characteristic of the 11S and 7S globulins. The three dimensional structure
      suggests that its high thermal stability is due to the cumulative effects of many
      factors and its good emulsifying property depended on the balance between its
      surface hydrophobicity and hydrophilicity.

PMID- 22868165
TI  - Direct potentiometric determination of diastase activity in honey.
AB  - A novel method for the determination of diastase activity is reported. The method
      is based on a direct potentiometric measurement of triiodide ion that is released
      when a starch-triiodide complex is hydrolysed by honey diastase. The increase of
      free triiodide ion concentration in a sample is found to be directly proportional
      to the diastase activity of the sample. A response mechanism of the platinum
      redox electrode is proposed, allowing a calculation of the diastase activity
      factor (F). The sensor and analyte parameters, including F, were obtained by
      least squares fitting of potentiometric data using the optimisation function of
      the Solver add-in of Microsoft Excel. The values of F obtained by the new direct
      potentiometric method were compared with those obtained using the standard
      Phadebas method (DN values), and the two values were found to agree within
      experimental error. Finally, the diastase activity of nine varieties of honey was
      determined using the novel method developed here.

PMID- 22868166
TI  - Studies on structures and activities of initial Maillard reaction products by
      electrospray ionisation mass spectrometry combined with liquid chromatography in
      processing of red ginseng.
AB  - Electrospray ionisation-mass spectrometry (ESI-MS) was applied to analyse the
      water-soluble extract of red ginseng (RG). Several new compounds were produced
      from the Maillard reaction during the steaming and drying process for preparing
      RG. Both the tandem electrospray ionisation (ESI-MS(n)) and Fourier transform ion
      cyclotron resonant mass spectrometric (FT-ICR-MS) data of these products proved
      that they were the initial Maillard reaction products (MRPs) of maltose with
      glutamic acid/aspartic acid, which were specific components in RG. In addition,
      their anti-diabetic and antioxidant activities were examined in vitro. The anti
      diabetic activities were evaluated by studying the alpha-glucosidase inhibition
      using ultrafiltration LC-MS/MS techniques, while the antioxidant activities were
      investigated by UPLC-ESI-MS method. The results demonstrated that four initial
      MRPs in RG were identified as alpha-glucosidase inhibitors, and showed marked
      scavenging effect on the hydroxyl radical ((.)OH). Based on these studies, the
      processing method of RG was improved to generate more active compounds.

PMID- 22868167
TI  - Effect of salt concentrations and drying methods on the quality and formation of
      histamine in dried milkfish (Chanos chanos).
AB  - The effects of salt concentrations (0-15.0%) and drying methods on the quality of
      dried milkfish were studied. The results showed that the levels of aerobic plate
      counts, total coliform, water activity, moisture contents, total volatile basic
      nitrogen (TVBN) and thiobarbituric acid (TBA) of the dried milkfish samples
      prepared with the same drying method decreased with increased salt
      concentrations. The samples prepared with the cold-air drying method had better
      quality in term of lower TVBN and TBA values than those of samples prepared with
      other drying methods. The histamine contents in all samples, except two, prepared
      with various salt concentrations by different drying methods were less than 1.9
      mg/100 g. Two unsalted samples prepared with hot-air drying at 35  degrees C and
      sun drying methods were found to contain histamine at levels of 249.7 and 67.4
      mg/100 g, respectively, which were higher than the potential hazard level of 50
      mg/100 g.

PMID- 22868168
TI  - Analyses of enrofloxacin, furazolidone and malachite green in fish products with
      surface-enhanced Raman spectroscopy.
AB  - Illegal fish drugs used in aquaculture have raised serious concerns due to their
      negative effects on public health and environment. In this study, surface
      enhanced Raman spectroscopy (SERS) was applied to analyze prohibited aquaculture
      drugs including enrofloxacin, furazolidone and malachite green (MG). Principal
      component analysis (PCA) and partial least squares (PLS) regression were used for
      spectral data analyses. For standard solutions, although no satisfied results
      were obtained for enrofloxacin, furazolidone and MG could be detected at 800 ng
      mL(-1) and 100 ng mL(-1), respectively. The R(2) of actual values vs. values
      predicted with PLS models for furazolidone and MG was 0.970 and 0.915,
      respectively. A clear segregation between furazolidone and MG was observed using
      PCA. Furazolidone and MG in tilapia fillets could be detected at 1 MUg g(-1) and
      200 ng g(-1), respectively, and their PLS models yielded R(2) of 0.922 and 0.843,
      respectively, showing potential for analyses of fish drugs with SERS.

PMID- 22868169
TI  - Cytotoxic and antioxidant constituents from Garcinia subelliptica.
AB  - Two new triterpenoids, garcinielliptones Q (1) and S (3), and a new
      phloroglucinol, garcinielliptone R (2), were isolated from the seed of Garcinia
      subelliptica. Their structures were established by analysis of their
      spectroscopic data. Phloroglucinol, garcinielliptone FC (4) from this plant
      exhibited a significant increase of antiproliferative effect, while 4 combined
      with cisplatin significantly caused decrease of cell inhibition induced by
      cisplatin in NTUB1. Exposure of NTUB1 cells to 4 cotreated with cisplatin for
      significantly decreased the amount of reactive oxygen species (ROS) than that of
      the total amount generated by 4 and cisplatin. These results suggested that 4
      could protect the cisplatin toxicity through reduction of ROS in NTUB1.
      Phloroglucinols, garcinielliptones, A (5) and F (7), and garsubelline A (6), from
      this plant, revealed ABTS radical cation scavenging activity and 5 displayed an
      inhibitory effect on xanthine oxidase. These finding showed that 5-7 may be used
      as antioxidants.

PMID- 22868170
TI  - Synthesis and comparison of 4-[18F]F-ADAM, 2-[18F]F-ADAM, N-Desmethyl-4-[18F]F
      ADAM and [18F]F-AFM as serotonin transporter imaging agents.
AB  - 4-[(18)F]F-ADAM (1a), 2-[(18)F]F-ADAM (2a), N-Desmethyl-4-[(18)F]F-ADAM (3a) and
      [(18)F]F-AFM (4a ) were synthesized in 1.7, 3.9, 2.9 and 0.6% yield (EOS),
      respectively, in a synthesis time of ~120 min from EOB. PET studies in rats
      showed that the maximum specific uptake ratios of 1a, 2a, 3a and 4a in midbrain
      were 3.86, 0.73, 0.35 and 2.23, respectively. Thus, in terms of radiochemical
      yield, specific binding and in vivo stability, 4-[(18)F]F-ADAM may be the most
      appropriate SERT imaging agent for human studies.

PMID- 22868171
TI  - Radioactive and geological analysis of airborne gamma spectrometric data for
      locating favorable traps for uranium prospecting in the Syrian desert (Area-1),
      Syria.
AB  - Statistical analysis has been applied to the airborne spectrometric data for the
      Syrian desert (Area-1), Syria in order to characterize and isolate the anomalous
      uranium radioactive zones. Equivalent uranium eU values vary between a minimum of
      0.01 and a maximum of 32.74 ppm. Uranium prospecting methodology recently
      proposed is successfully applied in order to explain the origin of the
      radioactive anomalies related to Area-1. The dominant geological conditions
      effectively contributing to the uranium radioactive anomalies in the study area
      have been determined through the analysis of five radioactive-geological
      profiles. Different favorable traps have been identified and localized for
      uranium prospecting. Those uranium traps merit further detailed exploration for
      determining their uranium potential with depth.

PMID- 22868172
TI  - Habituation and the reinforcing effectiveness of visual stimuli.
AB  - The term "sensory reinforcer" has been used to refer to sensory stimuli (e.g.
      light onset) that are primary reinforcers in order to differentiate them from
      other more biologically important primary reinforcers (e.g. food and water).
      Acquisition of snout poke responding for a visual stimulus (5 s light onset) with
      fixed ratio 1 (FR 1), variable-interval 1 min (VI 1 min), or variable-interval 6
      min (VI 6 min) schedules of reinforcement was tested in three groups of rats
      (n=8/group). The VI 6 min schedule of reinforcement produced a higher response
      rate than the FR 1 or VI 1 min schedules of visual stimulus reinforcement. One
      explanation for greater responding on the VI 6 min schedule relative to the FR 1
      and VI 1 min schedules is that the reinforcing effectiveness of light onset
      habituated more rapidly in the FR 1 and VI 1 min groups as compared to the VI 6
      min group. The inverse relationship between response rate and the rate of visual
      stimulus reinforcement is opposite to results from studies with biologically
      important reinforcers which indicate a positive relationship between response and
      reinforcement rate. Rapid habituation of reinforcing effectiveness may be a
      fundamental characteristic of sensory reinforcers that differentiates them from
      biologically important reinforcers, which are required to maintain homeostatic
      balance.

PMID- 22868173
TI  - Directing reprogramming to pluripotency by transcription factors.
AB  - The pluripotent state is governed by specifically expressed transcription factors
      forming a highly interconnected regulatory network in concert with more widely
      expressed transcription factors. The transcriptional network exhibits a
      hierarchical structure, with a small number of transcription factors playing an
      essential role in maintaining pluripotency and controlling the more numerous
      auxiliary transcription factors. When the set of master transcription factors
      comprising Oct4, Sox2, Klf4, and Myc is expressed ectopically in somatic cells,
      the transcriptional network is propelled to organize itself in such a way as to
      support a pluripotent state. These transcription factors play distinct but
      interdependent roles in remodeling gene expression by influencing the local
      chromatin status during reprogramming.

PMID- 22868174
TI  - Human disease modeling with induced pluripotent stem cells.
AB  - In the past few years, cellular programming, whereby virtually all human cell
      types, including those deep within the brain or internal organs, can potentially
      be produced and propagated indefinitely in culture, has opened the door to a new
      type of disease modeling. Importantly, many diseases or disease predispositions
      have genetic components that vary from person to person. Now cells from
      individuals can be readily reprogrammed to form pluripotent cells, and then
      directed to differentiate into the lineage and the cell type in which the disease
      manifests. Those cells will contain the genetic contribution of the donor,
      providing an excellent model to delve into human disease at the level of
      individuals and their genomic variants. To date, over fifty such disease models
      have been reported, and while the field is young and hurdles remain, these tools
      promise to inform scientists about the cause and cellular-molecular mechanisms
      involved in pathology, unravel the role of environmental versus hereditary
      factors driving disease, and provide an unprecedented tool for screening
      therapeutic agents that might slow or halt disease progression.

PMID- 22868175
TI  - The development of pluripotent stem cells.
AB  - Stem cell biology has many roots, and the current interest in the possible
      medical and pharmaceutical applications of pluripotent stem cells has far removed
      origins in the biology of a rare but peculiar type of tumor, the teratomas. The
      identification of their stem cells and their relationship to the early embryo
      paved the way, first in the mouse and later in humans, to the development of
      embryonic stem (ES) and induced pluripotent stem (iPS) cells, and to approaches
      for controlling their differentiations. More recently, the recognition of genetic
      change and culture adaptation of these cells after prolonged culture has returned
      us to those cancer roots.

PMID- 22868176
TI  - Reprogramming somatic cells towards pluripotency by cellular fusion.
AB  - Pluripotent cells arise within the inner cell mass (ICM) of mammals and have the
      potential to generate all cell types of the adult organism through a process of
      commitment and ordered differentiation. Despite many decades of investigation,
      the mechanisms that guide and stabilise cell fate choice as well as those that
      can be engineered to promote its reversal, remain only partially resolved.
      Reprogramming of somatic cells towards a pluripotent-like state can be achieved
      by several different experimental routes including nuclear transfer, the supply
      of a defined cocktail of transcription factors, or by fusing somatic cells with a
      pluripotent stem cell partner. These approaches have been used to demonstrate the
      remarkable intrinsic epigenetic plasticity of many terminally differentiated cell
      types, as well as to define the factors that are required for pluripotent
      conversion. In this review we summarise some recent advances using cell fusion
      based studies to better understand the basis of pluripotency and the epigenetic
      mechanisms that promote cell type inter-conversion.

PMID- 22868178
TI  - Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated
      multidrug efflux: design, synthesis, characterization and biological evaluation.
AB  - Bivalent ligands were designed on the basis of the described close proximity of
      the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The
      syntheses of 19 progesterone-adenine hybrids are described. Their abilities to
      inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic
      cells overexpressing P-glycoprotein were evaluated versus progesterone. The
      hybrid with a hexamethylene linker chain showed the best inhibitory potency. The
      efficiency of these progesterone-adenine hybrids depends on two main factors: (i)
      the nature of the linker and (ii) its attachment point on the steroid skeleton.

PMID- 22868177
TI  - The many roads to Rome: induction of neural precursor cells from fibroblasts.
AB  - The experimental induction of specific cell fates in related or unrelated
      lineages has fascinated developmental biologists for decades. The evaluation of
      altered cell fates in response to ectopic expression during embryonic development
      has been a standard assay for interrogating gene function. However, until
      recently examples of cell lineage conversions were limited to closely related and
      primitive cell types. The induction of pluripotency in fibroblasts prominently
      highlighted that combinations of transcription factors can be extremely powerful
      and are much more effective than single genes. On the basis of this conclusion we
      previously identified transcription factor combinations that directly induce
      functional neuronal cells from mesodermal and endodermal cells. This work has
      evoked numerous additional studies demonstrating direct lineage conversion into
      neural and other lineages. Here, we review the generation of neural progenitor
      cells from fibroblasts, which is the newest addition to the arena of induced cell
      types. Surprisingly, two fundamentally different approaches have been taken to
      induce this cell type, one direct approach and another that involves the
      intermediate generation of a partially reprogrammed pluripotent state.

PMID- 22868179
TI  - Obstetric complications in early psychosis: relation with family history of
      psychosis.
AB  - The people classified as being at ultra-high risk (UHR) of developing psychosis
      are expected to share many risk factors for psychosis with the patients diagnosed
      with schizophrenia, including an enhanced incidence of obstetric complications
      (OCs). This study set out to investigate the incidence and correlates of OCs in a
      sample of patients accessing an early intervention center. Patients' mothers were
      asked whether they had suffered from any somatic complication during pregnancy
      from a list of OCs with potential direct relevance to the physical wellbeing of
      the offspring. Out of 86 patients diagnosed with first-episode psychosis, 20
      (23%) cases were positive for the occurrence of severe OCs, as reported by their
      mothers during an interview; out of 83 UHR patients, 21 (25%) cases were positive
      for OCs. OCs were more common in individuals with a family history of psychosis
      than in those without such a history. OCs might interact with genetic
      vulnerability to increase the risk of psychosis. Lack of comparison to healthy
      controls is a limitation that decreases the value of these findings.

PMID- 22868180
TI  - Indicators+: a proposal for everyday peace indicators.
AB  - Many of the approaches to measuring peace favoured by international
      organisations, INGOs and donor governments are deficient. Their level of analysis
      is often too broad or too narrow, and their aggregated statistical format often
      means that they represent the conflict-affected area in ways that are meaningless
      to local communities. This article takes the form of a proposal for a new
      generation of locally organised indicators that are based in everyday life. These
      indicators are inspired by practice from sustainable development in which
      indicators are crowd sourced. There is the potential for these to become
      'indicators+' or part of a conflict transformation exercise as communities think
      about what peace might look like and how it could be realised. The article
      advocates a form of participatory action research that would be able to pick up
      the textured 'hidden transcript' found in many deeply divided societies and could
      allow for better targeted peacebuilding and development assistance.

PMID- 22868181
TI  - Genotypic characterization and evaluation of an antibiotic resistance of
      Trueperella pyogenes (Arcanobacterium pyogenes) isolated from milk of dairy cows
      with clinical mastitis.
AB  - Trueperella pyogenes, recently reclassified from the genus Arcanobacterium, is
      considered the causative agent of acute suppurative mastitis called summer
      mastitis. T. pyogenes produces a variety of known and putative virulence factors
      that include pyolysin and factors promoting adhesion to host cells. The objective
      of this study was to report the presence of virulence genes in T. pyogenes
      isolates that were identified as etiological agents of clinical mastitis in cows,
      as well as to determine antimicrobial resistance and distribution of selected
      determinants that can be associated with phenotypic resistance among these
      isolates. The presence of genes (plo, nanH, nanP, cbpA, fimA, fimC, fimE, fimG,
      tet(W), erm(X), erm(B)) was examined by conventional PCRs. Resistance to 10
      antimicrobial agents was determined by the broth microdilution method. Among T.
      pyogenes isolates of bovine mastitis origin the genes encoding all virulence
      factors occurred. Besides pyolysin gene plo, the fimA was the only gene detected
      in all isolates, whereas other virulence factor genes were found with different
      frequencies. Phenotypic antimicrobial resistance was observed to tetracycline
      (85.5% isolates) and erythromycin (9.1%). Isolates non-susceptible to
      erythromycin simultaneously exhibited increased MIC of pirlimycin. Beta-lactams
      were active against isolates. We found the correlation between the presence of
      tetracycline and macrolide resistance genes and corresponding resistance
      phenotype. Genotypic characterization of a large number of T. pyogenes isolates
      from different herds performed in this study may be useful in explanation, which
      virulence factors play a significant role in the establishment of bovine mammary
      gland infection.

PMID- 22868182
TI  - Decoration of Histophilus somni lipooligosaccharide with N-acetyl-5-neuraminic
      acid enhances bacterial binding of complement factor H and resistance to killing
      by serum and polymorphonuclear leukocytes.
AB  - The incorporation of N-acetyl-5-neuraminic acid (Neu5Ac), or sialic acid, onto
      surface components of some bacterial species may enhance their virulence. We have
      previously shown that Neu5Ac can be incorporated onto the lipooligosaccharide
      (LOS) of the bovine pathogen Histophilus somni, resulting in diminished antibody
      binding and enhanced serum resistance (Inzana et al., 2002. Infect. Immun. 70,
      4870). In the present study, we assessed the effect of sialylation of H. somni
      LOS on the interaction with bovine innate host defenses. Incubation of non
      sialylated H. somni with pre-colostral calf serum (PCS) resulted in dose
      dependent, complement-mediated killing of the bacteria by the alternative
      pathway. However, sialylated H. somni was significantly more resistant to killing
      at any of the concentrations of PCS used. Sialylated H. somni LOS activated and
      consumed less complement than non-sialylated LOS, as determined by reduction in
      hemolysis of opsonized red blood cells, and by Western blotting of C(3)
      activation products. Sialylated H. somni bound more factor H and iC(3)b and less
      C(3) than non-sialylated bacteria, as determined by enzyme-linked immunosorbent
      assay, supporting the deficiencies observed in complement activation and
      consumption by sialylated LOS. Sialylation of H. somni LOS inhibited both
      polymorphonuclear leukocyte phagocytosis of (3)H-thymidine-labeled bacteria and
      intracellular killing of the bacteria, compared to non-sialylated bacteria.
      Furthermore, sialylated H. somni bound less non-specific antibodies in normal
      bovine sera than non-sialylated bacteria. Therefore, sialylation of H. somni LOS
      had profound effects on resistance of the bacteria to innate bovine host
      defenses, which should be taken into consideration during in vitro studies of H.
      somni.

PMID- 22868183
TI  - Impact on delay times and characteristics of patients undergoing primary
      percutaneous coronary intervention in the southern metropolitan area of Barcelona
      after implementation of the infarction code program.
AB  - INTRODUCTION AND OBJECTIVES: A standardized protocol of emergent transfer for
      primary percutaneous coronary intervention for patients with ST elevation
      myocardial infarction, defined as the Infarction Code, was implemented in June
      2009 in the Catalan regional health system. The objective of this study was to
      evaluate the impact of the new protocol on delay times, number of procedures and
      clinical characteristics compared with the previous period in the population of
      patients referred to our hospital. METHODS: All consecutive patients undergoing
      primary percutaneous coronary intervention in our hospital were prospectively
      registered. The clinical characteristics, delay times and mortality in the follow
      up of the protocol implementation period (June 2009-May 2010) were analyzed and
      compared with the previous year (June 2008-May 2009). RESULTS: During the
      protocol period, 514 patients were included, compared with 241 in the previous
      year. Age, cardiovascular risk factors, anterior myocardial infarction and
      procedure characteristics were similar in the 2 groups. The first medical contact
      to balloon time was lower in the protocol period (median time 120 min vs 88 min;
      P<.001). Patients in the protocol period showed a trend toward less severe
      disease (Killip III, rescue angioplasty). The multivariate regression analysis
      showed a significant association between 1-year mortality and age, Killip class
      >= III at admission, anterior infarction and 3-vessel disease. CONCLUSIONS: The
      introduction of the Infarction Code program increased the number of patients
      treated by primary percutaneous coronary intervention with a reduction in delay
      times and better clinical characteristics at presentation. Full English text
      available from:www.revespcardiol.org.

PMID- 22868184
TI  - Intravenous thrombolysis in a stroke patient taking dabigatran.

PMID- 22868185
TI  - International forum from Afghanistan. Editorial.

PMID- 22868186
TI  - Postgraduate education in transfusion medicine in the absence of formal residency
      training: assessment of factors needed to develop and sustain a postgraduate
      diploma program.
AB  - BACKGROUND: Quality education in transfusion medicine is key to delivering a safe
      and cost-effective blood service, yet postgraduate residency programs are lacking
      in many resource-limited countries and regions. The first formal, accredited,
      postgraduate training program in transfusion medicine aimed at medical doctors
      was developed and implemented at the University of the Free State in
      Bloemfontein, South Africa, in 2008. In the context of high demand and limited
      resources, ensuring sustainability of postgraduate training programs is
      essential. STUDY DESIGN AND METHODS: A formal qualitative and semi-quantitative
      research approach was followed to determine and test the factors considered
      important in program sustainability, and consisted of a literature survey,
      followed by semi-structured interviews and a Delphi survey. RESULTS: Fifty-five
      factors were identified from the semi-structured interviews. During the Delphi
      survey, consensus was reached on 41 and stability declared on a further 13. These
      factors formed the basis of a structured model informing the sustainability
      aspects of a postgraduate program in transfusion medicine. CONCLUSION: Literature
      on program sustainability in the field of transfusion medicine is very limited.
      This study identified the key factors essential to the long-term viability of a
      postgraduate program in transfusion medicine and should find broad applicability
      in other resource-limited countries and regions. It is envisaged that this will
      enable such programs to reach a state of self-sufficiency while not being overly
      reliant on external funding and support.

PMID- 22868187
TI  - Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine among Mexican
      children.
AB  - BACKGROUND AND AIMS: Streptococcus pneumoniae infection continues to be a major
      source of morbidity and mortality in children in Mexico. The aim of this study
      was to evaluate the immune response to six serotypes in children <5 years of age
      after immunization with a 23-valent pneumococcal polysaccharide vaccine. METHODS:
      A prospective study was conducted among children aged from 18 months to 4 years.
      Pre- and postvaccination titers for the serotypes selected in this project
      demonstrate a substantial response among all age groups. RESULTS: We identified
      mild adverse events in 62% of the participants in this study. No serious adverse
      events were reported during the study. CONCLUSIONS: Pneumococcal polysaccharide
      vaccine produced adequate immunogenicity in all age groups evaluated.

PMID- 22868188
TI  - Extracellular matrix remodeling in Takayasu's arteritis: role of matrix
      metalloproteinases and adventitial inflammation.
AB  - Takayasu's arteritis (TA) is an inflammatory fibrosing arteritis affecting
      predominately the aorta and its main branches. Pathogenesis of this disease
      remains enigmatic. Despite the numerous studies, the role of adventitia in
      vascular lesion formation in the setting of TA has been ignored. Virtually
      nothing is known about the mechanism regulating inflammation in the adventitia in
      the setting of TA. The present study included subjects with Takayasu's arteritis
      and normal healthy control subjects. Isolated T cells from peripheral blood
      mononuclear cells (PBMCs) using nylon wool and HUT-78 (human cutaneous T lymphoma
      cell line) were stimulated with PHA for 24 h. Stimulated cell were fixed with
      paraformaldehyde and fractionated into membrane, cytosolic and nuclear fractions.
      These cellular fractions were co-cultured with human fibrosarcoma cell line (HT
      1080) and transcriptional expression of matrix metalloproteinases (MMP-1, 3, 9
      and TIMP-1) was determined using semiquantitative RT-PCR. Stimulation of MMPs
      TIMP synthesis by HT-1080 cells was mimicked by a membranous fraction derived
      from activated T-cell isolated from TA subjects and activated HUT-78 cells,
      whereas cytosolic and nuclear fractions were ineffective. In conclusion, for the
      first time we provide evidence for the presence of a cell surface-specific
      antigenic moiety on T-cells of TA subjects, which is responsible for activation
      of fibroblasts (cells predominantly present in adventitia) to enhance MMP
      production and, therefore, may lead to extracellular matrix degradation.

PMID- 22868189
TI  - Climate change and zoonotic infections in the Russian Arctic.
AB  - Climate change in the Russian Arctic is more pronounced than in any other part of
      the country. Between 1955 and 2000, the annual average air temperature in the
      Russian North increased by 1.2 degrees C. During the same period, the mean
      temperature of upper layer of permafrost increased by 3 degrees C. Climate change
      in Russian Arctic increases the risks of the emergence of zoonotic infectious
      diseases. This review presents data on morbidity rates among people, domestic
      animals and wildlife in the Russian Arctic, focusing on the potential climate
      related emergence of such diseases as tick-borne encephalitis, tularemia,
      brucellosis, leptospirosis, rabies, and anthrax.

PMID- 22868190
TI  - Frequent use of primary health care service in Greenland: an opportunity for
      undiagnosed disease case-finding.
AB  - OBJECTIVES: To estimate the age- and gender-specific consultation rates of
      patients who availed primary health care service in Greenland and to analyse
      contact patterns among patients in Nuuk. DESIGN: Observational and cross
      sectional register study using data captured from the medical records. MATERIALS
      AND METHODS: The number of patients specified by age and gender who had contacted
      the primary health care centres within the last year was identified using a
      statistic module applied to the electronic medical records system. The population
      as it was on the 1st of January 2011 was used as the background population. The
      age- and gender-specific consultation rates were calculated. Review of most
      recent contact was performed in a subsample of patients from Nuuk, and
      information of the type of contact and diagnoses was obtained. RESULTS: Eighty
      three percent of the population in Greenland had been in contact with the primary
      health care centre within the last year. Females were more frequent users than
      males. A subsample of 400 patients in Nuuk was identified. Personal contact was
      the most frequent type of consultation (75.8%), followed by telephone (14.8%) and
      e-mail (9.8%) consultations. Musculoskeletal symptoms accounted for the most
      frequent bases for diagnoses. CONCLUSION: More than 80% of the whole population
      has been in contact with the primary health care system within the last year.
      This indicates that opportunistic case-finding of chronic diseases such as
      diabetes, hypertension, etc. providing a possible strategy for decreasing the
      number of undiagnosed cases.

PMID- 22868191
TI  - A decade of research in Inuit children, youth, and maternal health in Canada:
      areas of concentrations and scarcities.
AB  - Inuit Canadians are on average about 20 years younger and have a 10-year lower
      life expectancy than other Canadians. While there have been improvements in Inuit
      health status over time, significant health disparities still remain. This paper
      will review the peer-reviewed literature related to Inuit child, youth, and
      maternal health between 2000 and 2010, investigate which thematic areas were
      examined, and determine what proportion of the research is related to each group.
      Establishing areas of research concentrations and scarcities may help direct
      future research where it is needed. We followed a systematic literature review
      and employed peer-reviewed research literature on child, youth, and maternal
      health which were selected from 3 sources, MEDLINE, CINAHL, and the Circumpolar
      Health Bibliographic Database. The resulting references were read, and summarized
      according to population group and thematic area. The thematic areas that emerged
      by frequency were: infectious disease; environment/environmental exposures;
      nutrition; birth outcomes; tobacco; chronic disease; health care; policy, human
      resources; interventions/programming; social determinants of health; mental
      health and wellbeing; genetics; injury; and dental health. The 72 papers that met
      the inclusion criteria were not mutually exclusive with respect to group studied.
      Fifty-nine papers (82%) concerned child health, 24 papers (33%) youth health, and
      58 papers (81%) maternal health. The review documented high incidences of illness
      and significant public health problems; however, in the context of these issues,
      opportunities to develop research that could directly enhance health outcomes are
      explored.

PMID- 22868192
TI  - The role of Indigenous knowledge in environmental health risk management in
      Yukon, Canada.
AB  - OBJECTIVES: This project aimed to gain better understandings of northern
      Indigenous risk perception related to food safety and to identify the role that
      Indigenous knowledge (IK) plays in risk management processes to support more
      effective and culturally relevant benefit-risk (B-R) management strategies. STUDY
      DESIGN: The project used an exploratory qualitative case study design to
      investigate the role and place of IK in the management of environmental
      contaminants exposure via consumption of traditional foods in Yukon First Nations
      (YFNs). METHODS: Forty-one semi-directive interviews with Traditional Food
      Knowledge Holders and Health and Environment Decision-makers were conducted. A
      review and analysis of organizational documents related to past risk management
      events for the issue was conducted. Thematic content analysis was used to analyze
      transcripts and documents for key themes related to the research question.
      RESULTS: There was a recognized need by all participants for better collaboration
      between scientists and YFN communities. YFNs have been involved in identifying
      and defining community concerns about past risk issues, setting a local context,
      and participating in communications strategies. Interviewees stressed the need to
      commit adequate time for building relationships, physically being in the
      community, and facilitating open communication. Conducting community-based
      projects was identified as critical for collaboration and for cooperative
      learning and management of these issues. CONCLUSIONS: The perception of
      "effective" benefit-risk management is significantly influenced by the efforts
      made to include local communities in the process. A set of common guiding
      principles within a process that brings together people and knowledge systems may
      provide a more effective way forward in cross-cultural, multiple knowledge system
      contexts for complex benefit-risk issues than a prescriptive rigid framework.

PMID- 22868193
TI  - Structural, morphological and surface characteristics of two types of octacalcium
      phosphate-derived fluoride-containing apatitic calcium phosphates.
AB  - Octacalcium phosphate (OCP) has been reported to stimulate bone regeneration
      during hydrolysis into hydroxyapatite (HA). The present study was designed to
      characterize structural, morphological and surface properties of fluoride
      containing apatitic calcium phosphates (CaP) obtained through OCP hydrolysis or
      direct precipitation of OCP in the presence of 12-230ppm of fluoride (F). The
      products were characterized by chemical analysis, X-ray diffraction (XRD), field
      emission scanning electron microscopy (FE-SEM), transmission electron microscopy
      (TEM), selected area electron diffraction (SAED) and Fourier transform infrared
      spectroscopy (FTIR) as well as measurements of surface area, solubility,
      osteoblastic activities and bovine serum albumin (BSA) adsorption. XRD analysis
      re-confirmed that both preparations yielded more apatitic CaP with a higher
      concentration of F. However, the co-precipitated products (CF-CaP) maintained the
      properties of OCP, in particular the solubility, whereas the hydrolysis products
      (HF-CaP) had the characteristics of fluoridated apatite. The crystals of plate
      like OCP were changed to the crystals of rod-like CF-CaP and small irregular HF
      CaP with the advance of the hydrolysis. The SAED analysis detected both OCP and
      apatite crystals even in the most hydrolyzed CF-CaP. Mouse bone marrow stromal ST
      2 cells grew better on CF-CaP compared with HF-CaP. BSA adsorption was inhibited
      on HF-CaP more than on CF-CaP. These results show that OCP produces
      physicochemically distinct apatitic fluoridated CaP during hydrolysis, regarding
      the structure, the crystal morphology and the protein adsorption, depending on
      the fluoride introduction route, which provides biologically interesting
      material.

PMID- 22868194
TI  - Microbubbles as biocompatible porogens for hydrogel scaffolds.
AB  - In this study, we explored the application of lipid-shelled, gas-filled
      microbubbles as a method for creating on-demand microporous hydrogels for
      cartilage tissue engineering. The technique allowed for homogenous distribution
      of cells and micropores within the scaffold, increasing the absorption
      coefficient of large solutes (70kDa dextran) over controls in a concentration
      dependent manner. The stability of the gas phase of the microbubbles depended on
      several factors, including the initial size distribution of the microbubble
      suspension, as well as the temperature and pressure during culture. Application
      of pressure cycles provided controlled release of the gas phase to generate fluid
      filled micropores with remnant lipid. The resulting microporous agarose scaffolds
      were biocompatible, leading to a twofold increase in engineered cartilage
      properties (E(Y)=492+/-42kPa for the bubble group vs. 249+/-49kPa for the bubble
      free control group) over a 42-day culture period. Our results suggest that
      microbubbles offer a simple and robust method of modulating mass transfer in cell
      seeded hydrogels through mild pressurization, and the methodology may be expanded
      in the future to include focused ultrasound for improved spatio-temporal control.

PMID- 22868195
TI  - Chemometric model for predicting retention indices of constituents of essential
      oils.
AB  - Quantitative structure-retention relationships (QSRRs) model was developed for
      predicting the gas chromatography retention indices of 169 constituents of
      essential oils. The ordered predictors selection algorithm was used to select
      three descriptors (one constitutional index and two edge adjacency indices) from
      4885 descriptors. The final QSRR model (model M3) with three descriptors was
      internal and external validated. The leave-one-out cross-validation, leave-many
      out cross-validation, bootstrapping, and y-randomization test indicated the final
      model is robust and have no chance correlation. The external validations
      indicated that the model M3 showed a good predictive power. The mechanistic
      interpretation of QSRR model was carried out according to the definition of
      descriptors. The results show that the larger molecular weight, the greater the
      values of retention indices. More compact structures have stronger intermolecular
      interactions between the components of essential oils and the capillary column.
      Therefore, the result meets the five principles recommended by the Organization
      for Economic Co-operation and Development (OECD) for validation of QSRR model,
      and it is expected the model can effectively predict retention indices of the
      essential oils.

PMID- 22868196
TI  - Partitioning of persistent organic pollutants (POPs) between human serum and
      breast milk: a literature review.
AB  - The literature was reviewed to assess the relationship between the lipid adjusted
      concentration in human serum and breast milk (expressed as the serum/milk ratio)
      of a broad range of POPs in paired samples. Thirteen studies were identified,
      including seven studies that reported serum/milk ratios for polychlorinated
      dibenzo-dioxins and -furans (PCDD/Fs), ten for polychlorinated biphenyls (PCBs),
      five for polybrominated diphenyl ethers (PBDEs), and five for organochlorine
      pesticides (OCPs). Mean serum/milk ratios ranged between 0.7 and 25 depending on
      the compound and congener. For PCDD/Fs, PCBs and PBDEs, a clear trend of
      increasing mean serum/milk ratio by increasing molar volume, hydrophobicity and
      number of halogen substitutes was observed. The mean serum/milk ratios reported
      by the 13 studies summarized here will aid comparison between human POPs exposure
      studies using either serum or milk samples. More studies are needed to allow a
      valid comparison between data obtained from analysis of breast milk and serum
      samples for a broader range of POPs. Furthermore such studies may shed light on
      compound specific factors as well as other determinants that may affect the
      partitioning and partition kinetics of POPs between serum and breast milk.

PMID- 22868197
TI  - Spontaneous pneumobilia and air in the pancreatic duct.

PMID- 22868198
TI  - The activities of Smad and Gli mediated signalling pathways in high-grade
      conventional osteosarcoma.
AB  - High-grade conventional osteosarcoma is a malignant tumour predominantly
      affecting adolescents and, despite multimodal intensive therapy, lethal for one
      third of the patients. Although there is currently detailed knowledge of normal
      skeletal development, this has not been integrated into research on the genesis
      of osteosarcoma. Recently we showed that the canonical Wnt pathway is not active
      in osteosarcoma and that its reactivation is disadvantageous to osteosarcoma
      cells. Since Wnt is regulating normal skeletogenesis together with other
      pathways, here we report on the activities of the bone morphogenic protein (BMP),
      the transforming growth factor beta (TGFbeta) and the hedgehog (Hh) pathways in
      osteosarcoma. Human osteosarcoma samples (n=210), benign bone tumours of
      osteoblastic lineage called osteoblastoma (n=25) and osteosarcoma cell lines
      (n=19) were examined. For pathway activity luciferase transcriptional reporter
      assays and gene and protein expression analyses were performed.
      Immunohistochemical analysis of phosphorylated Smad1 and Smad2, the intracellular
      effectors of BMP and TGFbeta, respectively, showed nuclear expression of both
      proteins in 70% of the osteosarcoma samples at levels comparable to
      osteoblastoma. Interestingly cases with lower expression showed significantly
      worse disease free survival. This may imply that drugs restoring impaired
      signalling pathways in osteosarcoma might change the tumour's aggressive clinical
      course, however targeted pathway modulation in vitro did not affect cell
      proliferation.

PMID- 22868199
TI  - Diffusion tensor imaging and tractography of the spinal cord: from experimental
      studies to clinical application.
AB  - Diffusion-weighted magnetic resonance imaging provides detailed information about
      biological structures. In particular, diffusion tensor imaging and diffusion
      tensor tractography (DTT) are powerful tools for evaluating white matter fibers
      in the central nervous system. We previously established a reproducible spinal
      cord injury model in adult common marmosets and showed that DTT could be used to
      trace the neural tracts in the intact and injured spinal cord of these animals in
      vivo. Recently, many reports using DTT to analyze the spinal cord area have been
      published. Based on the findings from our experimental studies, we are now
      routinely performing DTT of the human spinal cord in the clinic. In this review
      we outline the basic principles of DTT, and describe the characteristics,
      limitations, and future uses of DTT to examine the spinal cord.

PMID- 22868200
TI  - Improved regeneration after spinal cord injury in mice lacking functional T- and
      B-lymphocytes.
AB  - It is widely accepted that the immune system plays important functional roles in
      regeneration after injury to the spinal cord. Immune response towards injury
      involves a complex interplay of immune system cells, such as neutrophils,
      macrophages and microglia, T- and B-lymphocytes. We investigated the influence of
      the lymphocyte component of the immune system on the locomotor outcome of severe
      spinal cord injury in a genetic mouse model of immune suppression. Transgenic
      mice lacking mature T- and B-lymphocytes due to the recombination activating gene
      2 gene deletion (RAG2-/- mice) were subjected to severe compression of the lower
      thoracic spinal cord, with the wild-type mice of the same inbred background
      serving as controls. According to both the Basso Mouse Scale score and single
      frame motion analysis, the RAG2-/- mice showed improved recovery in comparison to
      control mice at six weeks after injury. Better locomotor function was associated
      with enhanced catecholaminergic and cholinergic reinnervation of the spinal cord
      caudal to injury and increased axonal regrowth/sprouting at the site of injury.
      Myelination of axons in the ventral column measured as g-ratio was more extensive
      in RAG2-/- than in control mice 6weeks after injury. Additionally, the number of
      microglia/macrophages was decreased in the lumbar spinal cord of RAG2-/- mice
      after injury, whereas the number of astrocytes was increased compared with
      controls. We conclude that T- and B-lymphocytes restrict functional recovery from
      spinal cord injury by increasing numbers of microglia/macrophages as well as
      decreasing axonal sprouting and myelination.

PMID- 22868201
TI  - Cerebralcare Granule(r) attenuates blood-brain barrier disruption after middle
      cerebral artery occlusion in rats.
AB  - Disruption of blood-brain barrier (BBB) and subsequent edema are major
      contributors to the pathogenesis of ischemic stroke, for which the current
      clinical therapy remains unsatisfied. Cerebralcare Granule(r) (CG) is a compound
      Chinese medicine widely used in China for treatment of cerebrovascular diseases.
      CG has been demonstrated efficacy in attenuating the cerebral microcirculatory
      disturbance and hippocampal neuron injury following global cerebral ischemia.
      However, the effects of CG on BBB disruption following cerebral ischemia have not
      been investigated. In this study, we examined the therapeutic effect of CG on the
      BBB disruption in a focal cerebral ischemia/reperfusion (I/R) rat model. Male
      Sprague-Dawley rats (250 to 300 g) were subjected to 1h middle cerebral artery
      occlusion (MCAO). CG (0.4 g/kg or 0.8 g/kg) was administrated orally 3h after
      reperfusion for the first time and then once daily up to 6 days. The results
      showed that Evans blue extravasation, brain water content, albumin leakage,
      infarction volume and neurological deficits increased in MCAO model rats, and
      were attenuated significantly by CG treatment. T2-weighted MRI and electron
      microscopy further confirmed the brain edema reduction in CG-treated rats.
      Treatment with CG improved cerebral blood flow (CBF). Western blot analysis and
      confocal microscopy showed that the tight junction proteins claudin-5, JAM-1,
      occludin and zonula occluden-1 between endothelial cells were significantly
      degradated, but the protein expression of caveolin-1, the principal marker of
      caveolae in endothelial cells, increased after ischemia, all of which were
      alleviated by CG treatment. In conclusion, the post-treatment with CG
      significantly reduced BBB permeability and brain edema, which were correlated
      with preventing the degradation of the tight junction proteins and inhibiting the
      expression of caveolin-1 in the endothelial cells. These findings provide a novel
      approach to the treatment of ischemic stroke.

PMID- 22868202
TI  - In silico screened Mycobacterium avium subsp. paratuberculosis (MAP) recombinant
      proteins upregulated under stress conditions are immunogenic in sheep.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of
      Johne's disease (JD) in ruminants. MAP is known to enter a dormant phase outside
      the host, typically on soil. In vitro experiments have reported regulation of
      certain MAP genes when exposed to stressors similar to what is thought to produce
      dormancy. It is believed that in vivo regulation of dormancy genes and associated
      proteins by MAP may play a role in evading the host defence mechanisms and induce
      the host immune response against these dormancy-related proteins. Five proteins
      encoded by dormancy-related genes that were previously found to be upregulated
      under stress conditions and predicted through in silico analysis to possess
      immune epitopes (three hypothetical proteins and two proteins involved in fatty
      acid metabolism) were selected. Recombinant proteins were produced, purified and
      evaluated by indirect enzyme-linked immunosorbent assay (ELISA) for
      immunogenicity using a panel of sera obtained from sheep unexposed and exposed to
      MAP. The antibody levels of the exposed group were significantly higher than the
      unexposed group (P<0.001). Individually, the five proteins were found to
      discriminate between sera from sheep exposed to MAP compared to unexposed sheep.
      At 91% diagnostic specificity, the diagnostic sensitivity of the recombinant
      antigen ELISA ranged from 24% to 42% and AUC(ROC) from 0.7015 to 0.8405.

PMID- 22868203
TI  - A defined intestinal colonization microbiota for gnotobiotic pigs.
AB  - Maximising the ability of piglets to survive exposure to pathogens is essential
      to reduce early piglet mortality, an important factor in efficient commercial pig
      production. Mortality rates can be influenced by many factors, including early
      colonization by microbial commensals. Here we describe the development of an
      intestinal microbiota, the Bristol microbiota, for use in gnotobiotic pigs and
      its influence on synthesis of systemic immunoglobulins. Such a microbiota will be
      of value in studies of the consequences of early microbial colonization on
      development of the intestinal immune system and subsequent susceptibility to
      disease. Gnotobiotic pig studies lack a well-established intestinal microbiota.
      The use of the Altered Schaedler Flora (ASF), a murine intestinal microbiota, to
      colonize the intestines of Caesarean-derived, gnotobiotic pigs prior to gut
      closure, resulted in unreliable colonization with most (but not all) strains of
      the ASF. Subsequently, a novel, simpler porcine microbiota was developed. The
      novel microbiota reliably colonized the length of the intestinal tract when
      administered to gnotobiotic piglets. No health problems were observed, and the
      novel microbiota induced a systemic increase in serum immunoglobulins, in
      particular IgA and IgM. The Bristol microbiota will be of value for highly
      controlled, reproducible experiments of the consequences of early microbial
      colonization on susceptibility to disease in neonatal piglets, and as a
      biomedical model for the impact of microbial colonization on development of the
      intestinal mucosa and immune system in neonates.

PMID- 22868204
TI  - [A different approach to the percutaneous nephrostomy by urologists].
AB  - INTRODUCTION: Percutaneous nephrostomy (PCN) tube placement is generally
      performed in radiologic departments worldwide. However, there are a few urologist
      directed studies about PCN performed with ultrasound guidance. Needle direction
      using a convex abdominal ultrasound probe might be difficult in unexperienced
      hands. In order to perform this procedure easily, we propose that a probe placed
      on flank or intercostal region and a long grooved needle director that never
      allows needle movement would be useful. We considered a transrectal ultrasound
      (TRUS) probe was suitable to resolve this issue. MATERIAL AND METHOD: From
      January 2007 to April 2011, a total of 113 percutaneous renal access (PRA) were
      performed using a TRUS probe in 102 patients, aged 20 to 84 years old. Because of
      the insufficient imaging capability of the TRUS probe in obese patients whose
      body mass index (BMI) greater than 30kg/m(2) were excluded. Forty two PRA were
      performed under local anesthesia and this group was named local anesthesia (LA)
      group. Seventy one PRA were performed for nephrostomy insertion under local
      anesthesia supplemented by deep sedation and this cluster was named deep sedation
      (DS) group. RESULTS: Targeted calyx puncture and guide wire placement was
      performed in all patients (100%) but success rate of tube insertion in each group
      was different. Successful PCN insertion rate was 69.1% (29 of 42 cases) in LA
      group and 95.8% (68 of 71 cases) in DS group. No major vascular injury and/or
      adjacent organ injury to bowel, liver, spleen or lung was seen in any patient.
      CONCLUSION: Guidance of TRUS probe, deep sedation, and modified dilators may
      offer a high success rate to the urologists with little experience in PCN
      insertion which they would find it difficult to perform.

PMID- 22868205
TI  - Ovarian response of prepubertal Murrah heifers to exogenous GnRH.
AB  - The aim of the current study was to evaluate the ovarian follicular response to
      GnRH at two dose levels in prepubertal Murrah buffalo heifers during hot-humid
      months. Heifers received 10 MUg (Group A, n=7) or 20 MUg (Group B, n=6) of GnRH
      during the growing phase of the dominant follicle (DF>6mm), as identified by
      pretreatment regular ultrasound scanning. A similar dose was repeated
      approximately 30 days later, again coinciding with another growing DF. Post
      treatment ovarian activity was studied by alternate day transrectal
      ultrasonography until 25 days post-second GnRH. In both groups, three types of
      response were recorded: formation of a corpus luteum (CL), luteinization of the
      follicle wall, i.e. luteinized follicle (LF) or no response (NR). Pooled data at
      GnRH injections revealed that the DF diameter in relation to the type of response
      in Group A heifers was, NR: 6.83 +/- 0.17 (n=3), LF: 8.10 +/- 0.67 (n=6) and CL:
      8.88 +/- 0.96 mm (n=5), while respective values in Group B heifers were 8.68 +/-
      0.44 mm (n=4), 9.37 +/- 0.46 (n=6) and 8.95 +/- 0.55 mm (n=2). The pattern of
      response was more evident in Group A but unpredictable in Group B. Corpora lutea
      developed in response to both the GnRH injections were short-lived. Mean maximum
      diameter of LFs in Groups A and B were 16.07 +/- 0.99 and 16.58 +/- 1.20 mm
      respectively and wave duration of these follicles in both groups was 23.33 +/-
      1.67 and 25.33 +/- 1.12 days, respectively. None of the heifers commenced
      cyclicity following regression of the CL or LF.

PMID- 22868206
TI  - Bioinformatic analysis of the Acinetobacter baumannii phage AB1 genome.
AB  - As one of the pathogens of hospital-acquired infections, Acinetobacter baumannii
      poses great challenges to the public health. A. baumannii phage could be an
      effective way to fight multi-resistant A. baumannii. Here, we completed the whole
      genome sequencing of the complete genome of A. baumannii phage AB1, which
      consists of 45,159 bp and is a double-stranded DNA molecule with an average GC
      content of 37.7%. The genome encodes one tRNA gene and 85 open reading frames
      (ORFs) and the average size of the ORF is 531 bp in length. Among 85 ORFs, only
      14 have been identified to share significant sequence similarities to the genes
      with known functions, while 28 are similar in sequence to the genes with function
      unknown genes in the database and 43 ORFs are uniquely present in the phage AB1
      genome. Fourteen function-assigned genes with putative functions include five
      phage structure proteins, an RNA polymerase, a big sub-unit and a small sub-unit
      of a terminase, a methylase and a recombinase and the proteins involved in DNA
      replication and so on. Multiple sequence alignment was conducted among those
      homologous proteins and the phylogenetic trees were reconstructed to analyze the
      evolutionary courses of these essential genes. From comparative genomics
      analysis, it turned out clearly that the frame of the phage genome mainly
      consisted of genes from Xanthomonas phages, Burkholderia ambifaria phages and
      Enterobacteria phages and while it comprises genes of its host A. baumannii only
      sporadically. The mosaic feature of the phage genome suggested that the
      horizontal gene transfer occurred among the phage genomes and between the phages
      and the host bacterium genomes. Analyzing the genome sequences of the phages
      should lay sound foundation to investigate how phages adapt to the environment
      and infect their hosts, and even help to facilitate the development of biological
      agents to deal with pathogenic bacteria.

PMID- 22868207
TI  - Phylogenetic relationships of the Cobitoidea (Teleostei: Cypriniformes) inferred
      from mitochondrial and nuclear genes with analyses of gene evolution.
AB  - The superfamily Cobitoidea of the order Cypriniformes is a diverse group of
      fishes, inhabiting freshwater ecosystems across Eurasia and North Africa. The
      phylogenetic relationships of this well-corroborated natural group and diverse
      clade are critical to not only informing scientific communities of the phylogeny
      of the order Cypriniformes, the world's largest freshwater fish order, but are
      key to every area of comparative biology examining the evolution of traits,
      functional structures, and breeding behaviors to their biogeographic histories,
      speciation, anagenetic divergence, and divergence time estimates. In the present
      study, two mitochondrial gene sequences (COI, ND4+5) and four single-copy nuclear
      gene segments (RH1, RAG1, EGR2B, IRBP) were used to infer the phylogenetic
      relationships of the Cobitoidea as reconstructed from maximum likelihood (ML) and
      partitioned Bayesian Analysis (BA). Analyses of the combined
      mitochondrial/nuclear gene datasets revealed five strongly supported monophyletic
      Cobitoidea families and their sister-group relationships:
      Botiidae+(Vaillantellidae+(Cobitidae+(Nemacheilidae+Balitoridae))). These
      recovered relationships are in agreement with previous systematic studies on the
      order Cypriniformes and/or those focusing on the superfamily Cobitoidea. Using
      these relationships, our analyses revealed pattern lineage- or ecological-group
      specific evolution of these genes for the Cobitoidea. These observations and
      results corroborate the hypothesis that these group-specific-ancestral ecological
      characters have contributed in the diversification and/or adaptations within
      these groups. Positive selections were detected in RH1 of nemacheilids and in
      RAG1 of nemacheilids and genus Vaillantella, which indicated that evolution of
      RH1 (related to eye's optic sense) and RAG1 (related to immunity) genes appeared
      to be important for the diversification of these groups. The balitorid lineage
      (those species inhabiting fast-flowing riverine habitats) had, as compared with
      other cobitoid lineages, significantly different dN/dS, dN and dS values for ND4
      and IRBP genes. These significant differences are usually indicative of weaker
      selection pressure, and lineage-specific evolution on genes along the balitorid
      lineage. Furthermore, within Cobitoidea, excluding balitorids, species living in
      subtropics had significantly higher dN/dS values in RAG1 and IRBP genes than
      those living in temperate and tropical zones. Among tropical cobitoids, genes
      COI, ND5, EGR2B, IRBP and RH1, had a significantly higher mean dS value than
      those species in subtropical and temperate groups. These findings suggest that
      the evolution of these genes could also be ecological-group-specific and may have
      played an important role in the adaptive evolution and diversification of these
      groups. Thus, we hypothesize that the genes included in the present study were
      actively involved in lineage- and/or ecological-group-specific evolutionary
      processes of the highly diverse Cobitoidea. These two evolutionary patterns, both
      subject to further testing, are hypothesized as integral in the diversification
      with this major clade of the world's most diverse group of freshwater fishes.

PMID- 22868209
TI  - The relationship between freely chosen cadence and optimal cadence in cycling.
AB  - PURPOSE: The main aim of this study was to compare the freely chosen cadence
      (FCC) and the cadence at which the blood lactate concentration at constant power
      output is minimized (optimal cadence [Copt]). The second aim was to examine the
      effect of a concomitant change of road incline and body position on FCC, the
      maximal external power output (Pmax), and the corresponding Copt. METHODS: FCC,
      Copt, and Pmax were analyzed under 2 conditions: cycling on level ground in a
      dropped position (LGDP) and cycling uphill in an upright position (UHUP). Seven
      experienced cyclists participated in this study. They cycled on a treadmill to
      test the 2 main hypotheses: Experienced cyclists would choose an adequate cadence
      close to Copt independent of the cycling condition, and FCC and Copt would be
      lower and Pmax higher for UHUP than with LGDP. RESULTS: Most but not all
      experienced cyclists chose an adequate cadence close to Copt. Independent of the
      cycling condition, FCC and Copt were not statistically different. FCC (82.1 +/-
      11.1 and 89.3 +/- 10.6 rpm, respectively) and Copt (81.5 +/- 9.8 and 87.7 +/-
      10.9 rpm, respectively) were significantly lower and Pmax was significantly
      higher (2.0 +/- 2.1%) for UHUP than for LGDP. CONCLUSION: Most experienced
      cyclists choose a cadence near Copt to minimize peripheral fatigue at a given
      power output independent of the cycling condition. Furthermore, it is
      advantageous to use a lower cadence and a more upright body position during
      uphill cycling.

PMID- 22868208
TI  - Renal LRP2 expression in man and chicken is estrogen-responsive.
AB  - In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an
      endocytic receptor that binds multiple ligands and is essential for a wide range
      of physiological processes. To gain new insights into the biology of this complex
      protein, we have initiated the molecular characterization of the LRP2 homolog
      from an oviparous species, the chicken (Gallus gallus). The galline LRP2 cDNA
      encodes a membrane protein of 4658 residues. Overall, the galline and human
      proteins are 73% identical, indicating that the avian gene has been well
      conserved over 300 million years. Unexpectedly, LRP2 transcript and protein
      levels in the kidney of females and estrogen-treated roosters were significantly
      higher than those in untreated males. The estrogen-responsiveness of avian LRP2
      may be related to the dramatic differences in lipoprotein metabolism between
      mature roosters and laying hens. Newly identified potential estrogen-responsive
      elements (ERE) in the human and galline LRP2 gene, and additional Sp1 sites
      present in the promoter of the chicken gene, are compatible with both direct
      estrogen induction via the classical ligand-induced ERE pathway and the indirect
      transcription factor crosstalk pathway engaging the Sp1 sites. In agreement with
      this assumption, estrogen induction of LRP2 was observed not only in primary
      cultured chicken kidney cells, but also human kidney cell lines. These findings
      point to novel regulatory features of the LRP2 gene resulting in sex-specific
      receptor expression.

PMID- 22868210
TI  - A bifasic response to cadmium stress in carrot: Early acclimatory mechanisms give
      way to root collapse further to prolonged metal exposure.
AB  - Very few studies have provided information about the effects of cadmium (Cd) at
      histoanatomical and ultrastructural levels, along with potential localization of
      the metal in planta. In particular, from this standpoint, almost nothing is known
      in Daucus carota L. (carrot), a particularly important species for in vitro and
      in vivo functional investigations. In this work we hypothesized that 36 MUM Cd,
      supplied for 1, 2, 3, 4, 7 and 14 days to 30-day-old in vitro-cultured plants,
      might induce an early acclimation, but a final collapse of roots and leaves. In
      fact, as a general feature, a biphasic root response to Cd stress actually took
      place: in the first phase (1-4 days of Cd exposure), the cytological and
      functional events observed - by light microscopy, TEM, epifluorescence, as well
      as by the time-course of thiol-peptide compounds - can be interpreted as
      acclimatory responses aimed at diminishing the movement of Cd across the root.
      The second phase (from 4 to 14 days of Cd exposure) was instead characterized by
      cell hypertrophy, cell-to-cell separation events, increase in alpha-beta-gamma
      tocopherol levels and, not least, endocytogenic processes, coupled with a
      dramatic drop in the amount of thiol-peptide compounds. These events led to a
      progressive root collapse, even if they did not ingenerate macro/microscopic
      injury symptoms in leaf blades and petioles.

PMID- 22868211
TI  - Proteomic analysis of rice anthers under salt stress.
AB  - Salinity is a major factor that limits rice production worldwide. Rice is
      considered generally to be sensitive to salt stress during the reproductive
      stage. To determine the molecular mechanisms of salt tolerance at the
      reproductive stage, anther proteomic patterns for two contrasting rice genotypes
      IR64 (salt sensitive) and Cheriviruppu (salt tolerant) under salt stress were
      compared. Plants were grown in a greenhouse and salt stress (100 mM NaCl) was
      imposed at the booting stage. Anther samples were collected from control and salt
      treated plants at the anthesis stage. The Na(+)/K(+) ratio in IR64 anthers under
      salt stress was >1.7 times greater than that under control conditions, whereas no
      significant change was observed in Cheriviruppu. We also observed an 83%
      reduction in IR64 pollen viability, whereas this reduction was only 23% in
      Cheriviruppu. Of 454 protein spots detected reproducibly on two-dimensional
      electrophoresis gels, 38 showed significant changes in at least one genotype in
      response to stress. Using Mass spectrometry (MALDI TOF/TOF) analysis, we
      identified 18 protein spots that were involved in several processes that might
      increase plant adaptation to salt stress, such as carbohydrate/energy metabolism,
      anther wall remodelling and metabolism, and protein synthesis and assembly. Three
      isoforms of fructokinase-2 were upregulated only in Cheriviruppu under salt
      stress. This upregulation might result in increased starch content in pollen,
      which would support pollen growth and development under salt stress. The results
      also suggested that anther and pollen wall remodelling/metabolism proteins
      contribute to the tolerance of rice to salt stress.

PMID- 22868212
TI  - Bombesin-like peptides stimulate growth hormone secretion mediated by the gastrin
      releasing peptide receptor in cattle.
AB  - This study was designed to determine the effects of bombesin-like peptides (BLPs)
      on the secretion of growth hormone (GH) and to characterize the receptor subtypes
      mediating these effects in cattle. Four experiments were conducted: (1) six
      steers were randomly assigned to receive intravenous (IV) bolus injections of 0,
      0.2, 1.0, 12.5 and 50.0 MUg/kg neuromedin C (NMC); (2) seven pre-weaned calves
      were IV injected with 1.0 MUg/kg NMC; (3) six steers were IV injected with
      2.5MUg/kg bovine gastrin-releasing peptide (GRP), 1.0 MUg/kg NMC combined with
      20.0 MUg/kg [d-Lys(3)]-GHRP-6 (an antagonist for the GH secretagogue receptor
      type 1a [GHS-R1a]), 1.0 MUg/kg NMC combined with 20.0 MUg/kg N-acetyl-GRP(20-26)
      OCH(2)CH(3) (N-GRP-EE, an antagonist for the GRP receptor), 20.0 MUg/kg N-GRP-EE
      alone, 1.0 MUg/kg neuromedin B (NMB); and (4) four rats were IV injected 1.0
      MUg/kg NMC. A serial blood sample was collected before and after injection.
      Plasma GH levels dose-dependently increased at 5 min after NMC injection and the
      minimal effective dose was 1.0 MUg/kg. Plasma GH level was elevated by GRP, but
      not by NMB. The NMC-induced elevation of GH was completely blocked by N-GRP-EE.
      The administration of NMC elevated GH level in pre-weaned calves but not in rats.
      Ghrelin level was unaffected by any treatments; and [d-Lys(3)]-GHRP-6 did not
      block the NMC-induced elevation of GH. The results indicate BLP-induced elevation
      of GH levels is mediated by the GRP receptor but not through a ghrelin/GHS-R1a
      pathway in cattle.

PMID- 22868213
TI  - Endothelium dependent expression and underlying mechanisms of des-Arg9-bradykinin
      induced B1R-mediated vasoconstriction in rat portal vein.
AB  - Endothelial dysfunction has been implicated in portal vein obstruction, a
      condition responsible for major complications in chronic portal hypertension.
      Increased vascular tone due to disruption of endothelial function has been
      associated with an imbalance in the equilibrium between endothelium-derived
      relaxing and contracting factors. Herein, we assessed underlying mechanisms by
      which expression of bradykinin B(1) receptor (B(1)R) is induced in the
      endothelium and how its stimulation triggers vasoconstriction in the rat portal
      vein. Prolonged in vitro incubation of portal vein resulted in time- and
      endothelium-dependent expression of B(1)R and cyclooxygenase-2 (COX-2).
      Inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI3K)
      significantly reduced expression of B(1)R through the regulation of transcription
      factors, activator protein-1 (AP-1) and cAMP response element-binding protein
      (CREB). Moreover, pharmacological studies showed that B(1)R-mediated portal vein
      contraction was reduced by COX-2, but not COX-1, inhibitors. Notably, activation
      of endothelial B(1)R increased phospholipase A(2)/COX-2-derived thromboxane A(2)
      (TXA(2)) levels, which in turn mediated portal vein contraction through binding
      to TXA(2) receptors expressed in vascular smooth muscle cells. These results
      provide novel molecular mechanisms involved in the regulation of B(1)R expression
      and identify a critical role for the endothelial B(1)R in the modulation of
      portal vein vascular tone. Our study suggests a potential role for B(1)R
      antagonists as therapeutic tools for diseases where portal hypertension may be
      involved.

PMID- 22868214
TI  - Distinct task-independent visual thresholds for egocentric and allocentric
      information pick up.
AB  - The dominant view of the ventral and dorsal visual systems is that they subserve
      perception and action. De Wit, Van der Kamp, and Masters (2011) suggested that a
      more fundamental distinction might exist between the nature of information
      exploited by the systems. The present study distinguished between these accounts
      by asking participants to perform delayed matching (perception), pointing
      (action) and perceptual judgment responses to masked Muller-Lyer stimuli of
      varying length. Matching and pointing responses of participants who could not
      perceptually judge stimulus length at brief durations remained sensitive to
      veridical stimulus length (egocentric information), but not the illusion
      (allocentric, context-dependent information), which was effective at long
      durations. Distinct thresholds for egocentric and allocentric information pick up
      were thus evident irrespective of whether perception (matching) or action
      (pointing) responses were required. It was concluded that the dorsal and ventral
      systems may be delineated fundamentally by fast egocentric- and slower
      allocentric information pick up, respectively.

PMID- 22868215
TI  - Reading aloud and the question of intent.
AB  - Must readers intend to process a word to activate various levels of
      representation, or is such processing simply triggered by the presentation of a
      word (i.e., is it "automatic")? This issue was addressed via the use of Besner
      and Care's Task Set paradigm. On each trial a cue, which indicated which of two
      tasks to perform appeared either before the target, or at the same time as the
      target. If subjects can process the target while preparing a task set, then the
      effect of a manipulated psycholinguistic factor should be absorbed into the time
      taken to process the cue. Despite robust main effects of SOA and word frequency
      there was no interaction between these factors when the task was to read aloud.
      This result implies that target processing is delayed until the subject knows
      what task to perform, and therefore that intention plays an important role when
      reading words aloud.

PMID- 22868216
TI  - Interleukin-17 and B cell-activating factor in Kawasaki disease and juvenile
      systemic lupus erythematosus.

PMID- 22868217
TI  - A study of plasma bicalutamide concentrations in hemodialysis patients.
AB  - Bicalutamide is an anti-androgen that is used worldwide to treat prostate cancer
      (CaP). However, there are no data on blood bicalutamide concentrations in
      hemodialysis (HD) patients with CaP. Therefore, we investigated the plasma levels
      of bicalutamide during the peridialysis period in this population. The study
      group included 5 HD patients with CaP who had been treated with bicalutamide (80
      mg/day) for at least 3 months. Blood samples were taken during and between HD
      sessions and the plasma concentrations of the active R enantiomer (R
      bicalutamide) were assessed using an HPLC assay. The plasma R-bicalutamide levels
      on the non-dialysis day were measured in 2 patients (patients 1 and 2)
      immediately before dosing and 8 and 24 h after dosing. These levels were 18,730,
      19,090 and 19,420 ng/ml (patient 1), and 4,522, 4,581, and 5,296 ng/ml (patient
      2), respectively. The mean plasma levels of R-bicalutamide in all 5 subjects just
      before HD, and 2 and 4 h after the start of HD were 8,726, 9,354 and 10,068
      ng/ml, respectively. These results show that bicalutamide does not accumulate and
      is not diluted in the blood circulation of HD patients when given at the normal
      dosage used in the general population.

PMID- 22868218
TI  - 2,4-Dichlorophenol removal in a solid-liquid two phase partitioning bioreactor
      (TPPB): kinetics of absorption, desorption and biodegradation.
AB  - The applicability of a sequencing batch two phase partitioning bioreactor (TPPB)
      to the biodegradation of a highly toxic compound, 2,4-dichlorophenol (DCP)
      (EC(50)=2.3-40 mgL(-1)) was investigated. A kinetic study of the individual
      process steps (DCP absorption into the polymer, desorption and biodegradation)
      was performed and, based on favourable absorption/desorption characteristics (DCP
      diffusivity of 6.6*10(-8)cm(2)s(-1)), the commercial polymer Tone P787 (Dow
      Chemical), was utilized as the sequestering phase for TPPB operation. Batch
      kinetic biodegradation tests were performed in both single- and two-phase modes,
      and the Haldane equation kinetic parameters were estimated (k=1.3*10(-2) mgDCP
      mgVSS(-1)h(-1), K(I)=35 mgDCPL(-1) and K(s)=18 mgDCPL(-1)), confirming the highly
      toxic nature of DCP. Consistent with these findings, operation of the single
      phase system showed that for an initial DCP concentration of 130 mg L(-1) the
      biomass was completely inhibited and DCP was not degraded, while the two-phase
      system achieved near-complete DCP removal. In sequencing batch mode the TPPB had
      a removal efficiency of 91% within 500 min for a feed of 320 mg L(-1), which
      exceeds the highest concentration previously degraded. These results have
      confirmed the effectiveness of the use of small amounts (5%, v/v) of inexpensive
      commercial polymers as the partitioning phase in TPPB reactors for the treatment
      of a highly toxic substrate at influent loads that are prohibitive for
      conventional single-phase operation, and suggest that similar detoxification of
      wastewater influents is achievable for other target cytotoxic substrates.

PMID- 22868219
TI  - Tumor B7-H1 and B7-H3 expression in squamous cell carcinoma of the lung.
AB  - BACKGROUND: Pulmonary squamous cell carcinoma has a poor prognosis, and new
      therapeutic targets are needed. The aberrant expression of the immunomodulatory
      proteins B7-H1 and B7-H3 by malignant cells may contribute to tumoral immune
      evasion. Data about the expression of these proteins by squamous cell carcinoma
      of the lung are limited. MATERIALS AND METHODS: Immunohistochemistry for B7-H1
      and B7-H3 was performed on 214 resected pulmonary squamous cell carcinoma
      specimens. RESULTS: At the last follow-up, 171 of 214 (80%) of patients were
      deceased (median survival time, 3.76 years). Forty-two (19.6%) of 214 cases
      showed positivity with B7-H1, with a range of 5% to 60% of cells that stained
      positively. A total of 189 (88.3%) of 214 cases showed positivity with B7-H3,
      with a range of 5% to 80% of cells staining positively. By using multivariate
      analysis, no degree of B7-H1 or B7-H3 positivity was significantly associated
      with patient outcome. CONCLUSIONS: Although B7-H1 and B7-H3 are not of
      independent prognostic value, they are commonly expressed on a subset of tumor
      cells in pulmonary squamous cell carcinomas. Known interaction of the B7-H
      proteins with cytotoxic T-lymphocyte antigen-4 may make them attractive candidate
      biomarkers for response to immunomodulatory therapeutics, eg, ipilimumab, and
      warrants further study.

PMID- 22868220
TI  - Clinical implications and added costs of incidental findings in an early
      detection study of lung cancer by using low-dose spiral computed tomography.
AB  - INTRODUCTION: To prospectively evaluate the frequency and spectrum of incidental
      findings (IF) in a 5-year lung cancer screening program with low-dose spiral
      computed tomography (CT) and to estimate the additional costs of their imaging
      workup incurred from subsequent radiologic follow-up evaluation. MATERIALS AND
      METHODS: A total of 519 asymptomatic volunteers were enrolled. All IFs were
      reported and were considered clinically relevant if they required further
      evaluations or with clinical implications if they required more than one
      additional diagnostic test for characterization or medical and/or surgical
      intervention. RESULTS: IFs were commonly found (59.2%, 307/519 participants at
      baseline and 5.3% per year at 5-year follow-up [123 participants of 2341 LDsCT
      exams performed during follow-up], with an overall rate of 26.3%). IFs were
      categorized as previously unknown clinically relevant in 52 (10.0%) individuals
      at baseline. Of these, 36 (6.9%) individuals had IFs with clinical implications
      (10 clinically relevant, of which 6 had clinical implications, detected during
      the subsequent 5-year follow-up). The most common recommendations were for
      additional imaging of the thyroid and kidneys. Additional imaging was mainly
      performed by ultrasound (43/68 [63.2%]). Subsequent surgical intervention
      resulted from these findings in 7 (1.5%) subjects. Six malignancies were
      diagnosed (rate, 0.2% per year). Costs of subsequent radiologic follow-up studies
      were calculated as ?4644.56 [U.S. $6575.04] at baseline and ?1052.30 [U.S.
      $1489.69] at 5-year follow-up (average added costs per participant ?8.95 [U.S.
      $12.67] and ?2.25 [U.S. $3.19], respectively). CONCLUSIONS: Low-dose spiral CT
      commonly detects IFs. Some of these require further investigations to assess
      their clinical relevance. Although such IFs add little clinical benefit to the
      screening intervention, moderate incremental costs are incurred based on
      additional radiologic procedures generated during short-term follow-up, given the
      potential for positive effects on patient care.

PMID- 22868221
TI  - Chemoradiotherapy for locoregional recurrence of non-small-cell lung cancer after
      surgical resection: a retrospective analysis.
AB  - BACKGROUND: Even if non-small-cell lung cancer (NSCLC) is diagnosed early and
      resected, recurrence is common. Uncertainty exists about the optimal treatment of
      locoregional recurrence. In fit patients with locoregional recurrence,
      chemoradiotherapy is sometimes offered, but no data exist about the feasibility
      and efficacy of this approach. We retrospectively collected data from patients
      treated this way to assess their outcomes and to identify prognostic factors.
      PATIENTS AND METHODS: Databases of The Ottawa Hospital Cancer Centre (TOHCC) (N =
      5791) and the Princess Margaret Hospital (PMH) (N = 2225) were screened to
      identify patients with recurrent NSCLC after curative resection who were offered
      curative-intent chemoradiotherapy. Selected patients' charts were reviewed.
      RESULTS: Thirty patients fit our search criteria. The median disease-free
      interval was 15 months (2-33 months) and stage at recurrence was mainly T0 (n =
      25 [83%]), N2 (n = 25 [83%]), and M0 (n = 29 [97%]). The median radiation dose
      given at recurrence was 63.5 Gy (26-66 Gy). Chemotherapy included a platinum
      agent in all cases, mostly a platinum-vinorelbine doublet (n = 14 [47%]), at a
      median of 3 cycles, (1-6 cycles) 2 of which were concurrent (0-3 cycles).
      Toxicities were as expected from thoracic chemoradiotherapy, with 7 cases of
      grade 4 toxicities and no treatment-related deaths. Median follow-up was 22
      months (1.5-88 months). Median survival after recurrence was 26.9 months. No
      prognostic factors were identified. CONCLUSION: Chemoradiotherapy for
      locoregional recurrent NSCLC is practiced sporadically. This treatment is
      feasible for highly selected patients, and in our cohort, it allowed for a
      significantly higher than expected survival. No prognostic factors were
      identified. Chemoradiotherapy for locoregional NSCLC should be examined in a
      prospective trial.

PMID- 22868222
TI  - Evaluating the impact of bevacizumab maintenance therapy on overall survival in
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: In patients with advanced-stage non-small-cell lung cancer (NSCLC)
      with nonsquamous histology, bevacizumab maintenance therapy after initial
      combination with platinum-based chemotherapy has been approved in the United
      States and Europe. In this study, a comparative effectiveness analysis of
      bevacizumab maintenance therapy after initial chemotherapy with bevacizumab is
      described. METHODS: A retrospective analysis of patients treated in 17 community
      oncology practices across the United States was conducted. Inclusion criteria
      consisted of patients with stage IIIb or IV disease who received bevacizumab
      maintenance after an initial first-line induction regimen. Overall survival (OS)
      was evaluated by using the method of Kaplan-Meier and Cox proportional hazard
      modeling. To control for selection bias that is inherent in observational
      studies, an 18-week landmark and propensity score analysis was conducted. The
      hazard ratio (HR) for OS was then evaluated in a sensitivity analysis. RESULTS: A
      total of 272 patients with advanced-stage NSCLC met the inclusion criteria. Only
      74 (27.2%) patients received bevacizumab maintenance therapy. Patients in the
      bevacizumab maintenance group tended to be younger and fitter, with a more
      favorable disease profile, which resulted in an improvement in the crude
      unadjusted OS (23.1 vs. 10.3 months; hazard ratio (HR) 0.44 [95% CI, 0.32-0.59]).
      Landmark and propensity score analyses supported the finding of a reduced risk of
      death with bevacizumab maintenance therapy (HR 0.52 [95% CI, 0.37-0.73] for
      landmark analyses and HR 0.70 [95% CI, 0.39-1.28] for propensity score analyses).
      CONCLUSIONS: Bevacizumab maintenance therapy contributed to an OS benefit in this
      retrospective sample of patients with NSCLC, even after multiple statistical
      adjustments for selection bias.

PMID- 22868223
TI  - Effect of a contralateral lesion on neurological recovery from stroke in rats.
AB  - PURPOSE: Clinical studies suggest a correlation between changes in activity of
      the contralesional cerebral cortex and spontaneous recovery from stroke, but
      whether this is a causal relationship is uncertain. METHODS: Young adult Sprague
      Dawley male rats underwent unilateral or bilateral permanent distal middle
      cerebral artery occlusion (dMCAO). Infarct volume was determined by 2,3,5
      triphenyltetrazolium chloride (TTC) staining 24 hr after dMCAO, and functional
      outcome was assessed 1-28 days after dMCAO using the ladder rung walking and limb
      placing tests. RESULTS: Infarct volume was unchanged, but functional neurological
      deficits were reduced 1 day after bilateral compared to unilateral dMCAO.
      CONCLUSIONS: Activity in the contralesional cerebral cortex may inhibit
      functional motor recovery after experimental stroke.

PMID- 22868224
TI  - Inter-hemispheric coupling changes associate with motor improvements after
      robotic stroke rehabilitation.
AB  - PURPOSE: In the chronic phase of stroke brain plasticity plays a crucial role for
      further motor control improvements. This study aims to assess the brain plastic
      reorganizations and their association with clinical progresses induced by a robot
      aided rehabilitation program in chronic stroke patients. METHODS: 7 stroke
      patients with an upper limb motor impairment in chronic phase underwent a multi
      modal evaluation before starting and at the end of a 12-week upper-limb
      neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and
      performance indices of hand movement performance (isometric pinch monitored
      through a visual feedback) were collected. Cerebral reorganizations were
      characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional
      and contralesional resting state properties investigating both bipolar
      derivations overlying the middle cerebral artery territory and the primary
      somatosensory sources (S1) obtained through the Functional Source Separation
      (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh)
      at rest were measured and correlated with clinical and hand control robot-induced
      improvements. RESULTS: After the robotic rehabilitation we found an improvement
      of FMAS scores and hand motor control performance and changes of brain
      connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement
      of motor performance correlated with the modulation of the interhemispheric S1
      coherence in the high beta band (24-33 Hz). CONCLUSIONS: Recently it has been
      shown that an upper limb robot-based rehabilitation improves motor performance in
      stroke patients. We confirm this potential and demonstrate that a robot-aided
      rehabilitation program induces brain reorganizations. Specifically,
      interhemispheric connectivity between primary somatosensory areas got closer to a
      'physiological level' in parallel with the acquisition of more accurate hand
      control.

PMID- 22868226
TI  - [Characteristics and management of early breast cancer in patients aged 80 years
      and older: retrospective study].
AB  - BACKGROUND: The number of elderly patients with breast cancer is increasing, and
      a large proportion of these older patients do not receive conventional treatment.
      Clinical and biological characteristics of tumours at this age and survival
      according to local or systemic therapy were analysed. MATERIAL AND METHOD: A
      total of 96 consecutive early breast cancer patients over 80 years of age
      diagnosed in our Unit between January 2002 and September 2008 were
      retrospectively investigated. Of them, 54 underwent surgery with or without
      adjuvant hormonal treatment, and 42 received primary hormonal therapy. RESULTS:
      Tumours of patients 80 years old or older had more favourable biological
      characteristics, including expression of steroid receptors, and absence of c-erb
      B2 expression. Overall survival was 50 months for the group subjected to surgery,
      and 44 months for the group who did not undergo surgery. The survival free of
      local recurrence in the surgery group was 44 months, whereas it was 18 months in
      the non-surgery group. CONCLUSION: In a cohort of patients aged 80 years and
      older, survival was similar in those who received hormonal or surgical therapy,
      although the former had a shorter period of progression-free survival or local
      recurrence.

PMID- 22868225
TI  - Methylation of arsenic by recombinant human wild-type arsenic (+3 oxidation
      state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role
      of glutathione.
AB  - Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the
      pathway for methylation of arsenicals. A common polymorphism in the AS3MT gene
      that replaces a threonyl residue in position 287 with a methionyl residue
      (AS3MT/M287T) occurs at a frequency of about 10% among populations worldwide.
      Here, we compared catalytic properties of recombinant human wild-type (wt) AS3MT
      and AS3MT/M287T in reaction mixtures containing S-adenosylmethionine, arsenite
      (iAs(III)) or methylarsonous acid (MAs(III)) as substrates and endogenous or
      synthetic reductants, including glutathione (GSH), a thioredoxin reductase
      (TR)/thioredoxin (Trx)/NADPH reducing system, or tris (2-carboxyethyl) phosphine
      hydrochloride (TCEP). With either TR/Trx/NADPH or TCEP, wtAS3MT or AS3MT/M287T
      catalyzed conversion of iAs(III) to MAs(III), methylarsonic acid (MAs(V)),
      dimethylarsinous acid (DMAs(III)), and dimethylarsinic acid (DMAs(V)); MAs(III)
      was converted to DMAs(III) and DMAs(V). Although neither enzyme required GSH to
      support methylation of iAs(III) or MAs(III), addition of 1mM GSH decreased K(m)
      and increased V(max) estimates for either substrate in reaction mixtures
      containing TR/Trx/NADPH. Without GSH, V(max) and K(m) values were significantly
      lower for AS3MT/M287T than for wtAS3MT. In the presence of 1mM GSH, significantly
      more DMAs(III) was produced from iAs(III) in reactions catalyzed by the M287T
      variant than in wtAS3MT-catalyzed reactions. Thus, 1mM GSH modulates AS3MT
      activity, increasing both methylation rates and yield of DMAs(III). AS3MT
      genotype exemplified by differences in regulation of wtAS3MT and AS3MT/M287T
      catalyzed reactions by GSH may contribute to differences in the phenotype for
      arsenic methylation and, ultimately, to differences in the disease susceptibility
      in individuals chronically exposed to inorganic arsenic.

PMID- 22868227
TI  - Severe Bickerstaff's encephalitis treated with Rituximab: serum and CSF GQ1b
      antibodies.
AB  - Bickerstaff's encephalitis is a syndrome of ophthalmoplegia, ataxia and impaired
      consciousness commonly associated with serum GQ1b antibodies. We describe a
      patient with seropositive Bickerstaff's encephalitis who did not respond either
      to plasma exchange or intravenous immunoglobulin but recovered following adjunct
      treatment with the anti-CD 20 monoclonal antibody, Rituximab. There was a
      concomitant reduction in serum GQ1b antibodies associated with improvement.
      Interestingly, GQ1b antibody was also detected in CSF. These findings have
      potentially significant clinical and immunopathological implications.

PMID- 22868228
TI  - N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptor.
AB  - A series of potent antagonists of the ion channel transient receptor potential A1
      (TRPA1) was developed by modifying lead structure 16 that was discovered by high
      throughput screening. Based on lead compound 16, a SAR was established, showing a
      narrow region at the nitro-aromatic R(1) moiety and at the warhead, while the
      R(2) side had a much wider scope including ureas and carbamates. Compound 16
      inhibits Ca(2+)-activated TRPA1 currents reversibly in whole cell patch clamp
      experiments, indicating that under in vivo conditions, it does not react
      covalently, despite its potentially electrophilic ketone.

PMID- 22868229
TI  - A fluorescent reporter of ATP binding-competent receptor kinases.
AB  - ERBB receptor kinases play a crucial role in normal development and cancer
      malignancies. A broad range of modifications creates receptor subpopulations with
      distinct functional properties in live cells. Their apparent activation state,
      typically assayed by tyrosine phosphorylation of substrates, reflects a complex
      equilibrium of competing reactions. With the aim of developing optical tools to
      investigate ERBB populations and their state of activation, we have synthesized a
      fluorescent 'turn-on' probe, DMAQ, targeting the ERBB ATP binding pocket. Upon
      binding, probe emission increases due to the hydrophobic environment and
      restricted geometry of the ERBB2 kinase domain, facilitating the analysis of
      receptor states at low occupancy and without the removal of unbound probes.
      Cellular ERBB2 autophosphorylation is inhibited with saturation kinetics that
      correlate with the increase in probe fluorescence. Thus, DMAQ is an example of a
      new generation of 'turn-on' probes with potential applications in querying
      receptor kinase populations both in vitro and in live cells.

PMID- 22868230
TI  - Murine GASP-1 N-glycosylation is not essential for its activity on C2C12 myogenic
      cells but alters its secretion.
AB  - BACKGROUND/AIMS: Growth and differentiation factor-associated serum protein-1
      (GASP-1) is a secreted protein known to be capable of binding and inhibiting the
      activity of several TGF-beta family members, including myostatin. The present
      study was designed to characterize murine GASP-1 post-translational modifications
      and to determine their influence on the biological activity of GASP-1. METHODS:
      We describe herein the site-directed mutagenesis of single N-glycosylation sites
      and combinations of them in 4 mutants of murine GASP-1. RESULTS: In vitro and in
      vivo analysis revealed that GASP-1 is a glycoprotein containing 2 N-glycans and
      several mucin-type O-glycans. Treatments by the recombinant murine GASP-1 protein
      enhance C2C12 proliferation and differentiation by inhibition of the myostatin
      pathway. The loss of N-glycans leads to a decrease in protein secretion rate but
      does not affect its ability to activate myogenesis. CONCLUSION: Analysis of
      structure-function relationships of murine GASP-1 provides insights into the
      involvement of the carbohydrate moiety of mGASP-1 on its biological activity.

PMID- 22868231
TI  - Physicochemical characterization of GBV-C E1 peptides as potential inhibitors of
      HIV-1 fusion peptide: interaction with model membranes.
AB  - Four peptide sequences corresponding to the E1 protein of GBV-C:
      NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10) and
      QAGLAVRPGKSAAQLVGE (P18) were studied as they were capable of interfering with
      the HIV-1 fusion peptide (HIV-1 FP). In this work, the surface properties of the
      E1 peptide sequences are investigated and their physicochemical characterization
      is done by studying their interaction with model membranes; moreover, their
      mixtures with HIV-1 FP were also studied in order to observe whether they are
      capable to modify the HIV-1 FP interaction with model membranes as liposomes or
      monolayers. Physicochemical properties of peptides (pI and net charge) were
      predicted showing similarities between P7 and P8, and P10 and HIV-1 FP, whereas
      P18 appears to be very different from the rest. Circular dichroism experiments
      were carried out showing an increase of the percentage of alpha-helix of P7 and
      P8 when mixed with HIV-1 FP corroborating a conformational change that could be
      the cause of their inhibition ability. Penetration experiments show that all the
      peptides can spontaneously insert into phospholipid membranes. Analysis of
      compression isotherms indicates that the peptides interact with phospholipids and
      the E1 peptides modify the compression isotherms of HIV-1 FP, but there is one of
      the peptides that excelled as the best candidate for inhibiting the activity of
      HIV-1 FP, P7, and therefore, that could be potentially used in future anti-HIV-1
      research.

PMID- 22868232
TI  - Screening paediatric rectal forms of azithromycin as an alternative to oral or
      injectable treatment.
AB  - The aim of this study was to identify a candidate formulation for further
      development of a home or near-home administrable paediatric rectal form of a
      broad-spectrum antibiotic - specially intended for (emergency) use in tropical
      rural settings, in particular for children who cannot take medications orally and
      far from health facilities where injectable treatments can be given.
      Azithromycin, a broad-spectrum macrolide used orally or intravenously for the
      treatment of respiratory tract, skin and soft tissue infections, was selected
      because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro
      solubility and stability in physiologically relevant conditions were studied.
      Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels,
      polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were
      assessed for in vitro dissolution and in vivo bioavailability in the rabbit.
      Azithromycin PEG suppository appears to be a promising candidate.

PMID- 22868233
TI  - The impact of training set data distributions for modelling of passive intestinal
      absorption.
AB  - This study presents regression and classification models to predict human
      intestinal absorption of 645 drug and drug like compounds using percentage human
      intestinal values from the published dataset by Hou et al. (2007c). The problem
      with this dataset and other datasets in the literature is there are more highly
      than poorly absorbed compounds. Any models developed using these datasets will be
      biased towards highly absorbed compounds and not applicable for use in industry
      where now more compounds are likely to be poorly absorbed. The study compared two
      training sets, TS1, a balanced (50:50) distribution of highly and poorly absorbed
      compounds created by under-sampling the majority high absorption compounds, with
      TS2, a randomly selected training set with biased distribution towards highly
      absorbed compounds. The regression results indicate that the best models were
      those developed using the balanced dataset (TS1). Also for classification, TS1
      led to the most accurate models and the highest specificity value of 0.949. In
      comparison, TS2 led to the highest sensitivity with a value of 0.939. Thus, under
      sampling the majority class of the highly absorbed compounds leads to a balanced
      training set (TS1) that can achieve more applicable in silico regression and
      classification models for the use in the industry.

PMID- 22868234
TI  - Cholorpheniramine tannate complexes: physicochemical, chemometric, and taste
      masking evaluation.
AB  - The focus of present investigation was to evaluate the tannic acid (TA) complexes
      of cholorpheniramine maleate (CPM) and characterize it by a variety of
      physicochemical, dissolution, and electronic tongue methods. The complexes were
      prepared in various molar ratios by solvent evaporation method. They were
      characterized by spectroscopic, thermal, powder X-ray, electronic tongue,
      solubility and dissolution methods. FTIR (infrared red) spectra showed complex
      formation between the TA and CPM. Complex formation has significantly lowered the
      drug solubility and sustained its release for more than 24 h in phosphate buffer
      pH 6.8. On the contrary, the release was much faster in the presence of Avicel PH
      113 in the same molar ratio complex. The complex formulation has suppressed the
      bitter taste of CPM as indicated by Euclidean distance in electronic tongue
      evaluation. NIR-CI (near infrared chemical imaging) showed lower skew value that
      indicated the homogenous distribution of formulation components. The chemometric
      models were also developed using the NIR data. The model based on second
      derivative data was better in predicting the TA and CPM loading as indicated by
      higher values of R, R(2) and lower values of root mean square error and standard
      errors. Furthermore, it has a better accuracy and less biased in comparison to
      other models. In conclusion, the CPM tannate has a sustained release behavior and
      excipients play a major role in modifying its release. Additionally, the
      complexes with varying molar ratio of tannate to CPM have differential taste
      masking abilities than that of the pure drug.

PMID- 22868235
TI  - Application of Langmuir-Blodgett film technology on studying the formulation of
      self-microemulsifying drug delivery system (SMEDDS).
AB  - The polarity of oleic acid, medium-chain triglyceride and their mixtures with
      different ratios was determined by LB film technology. Then the particle diameter
      after emulsifying in water when these different oils were mixed with Cremophor EL
      35 respectively was assayed. Then three formulations of SMEDDS using different
      oils were prepared. And their surface pressure-area isotherm curves and Gibbs
      change (DeltaG) were investigated. The results showed that flexibility of LB film
      was much better when oil with lower polarity was used to prepare the SMEDDS. And
      this group of SMEDDS which has low Gibbs change (DeltaG) was more stable with
      appropriate composition of oil, surfactant and co-surfactant. It can be concluded
      that LB film technology could be applied on the preliminary formulation study of
      SMEDDS. Our study may provide some theoretical basis and methods of formulation
      selection of SMEDDS.

PMID- 22868236
TI  - Good penetration of moxifloxacin into human abscesses.
AB  - Abscesses are often treated with antibiotics in addition to incision or when
      incision is unfeasible, but accurate information about antibiotic abscess
      penetration in humans is missing. This study aimed at evaluating the penetration
      of moxifloxacin into human abscesses. After administration of a single dose of
      400 mg moxifloxacin, drug concentrations were measured in 10 differently located
      abscesses at incision, and in plasma over 8 h. At incision performed 0.9-4.8 h
      after administration, moxifloxacin concentrations in abscesses ranged from <=0.01
      to 9.2 mg/l (1.9 +/- 3.4 mg/l), indicating pronounced drug accumulation in some
      abscesses. The degree of abscess penetration could not be explained by covariates
      like the ratio of surface area to volume or pH of abscesses, or by moxifloxacin
      plasma concentrations. Concluding, moxifloxacin was detectable in most abscesses
      and may be a useful antibiotic for this indication. However, antibiotic abscess
      penetration was highly variable and unpredictable, suggesting surgical abscess
      incision whenever possible.

PMID- 22868237
TI  - Repeated high-intensity running and sprinting in elite women's soccer
      competition.
AB  - BACKGROUND: To the authors' knowledge, no study has investigated the concurrent
      repeated, high-intensity (RHIA) and repeated-sprint activity (RSA) of
      intermittent team-sport competition. PURPOSE: In this study, they report on the
      RSA of elite women's football competition. In addition, they describe the nature
      of RHIA (eg, striding and sprinting activities) that involve a high energy cost
      and are associated with short (ie, <=20 s) recovery periods. METHODS: Thirteen
      elite women soccer players underwent video-based time-motion analysis on 34
      occasions during national and international standard matches. RSA and RHIA were
      defined as successive (ie, 2) sprints or striding and sprinting efforts that
      occurred with <=20 s between efforts. RESULTS: The number of RSA and RHIA bouts
      performed was similar between the first and second halves of matches. Sprinting
      and striding/sprinting durations tended to remain relatively stable irrespective
      of the number of efforts in an RSA or RHIA bout or the period of play. However,
      recovery duration between efforts increased in the second half, when a greater
      number of efforts were performed per bout. CONCLUSION: These findings suggest
      that first- to second-half reductions in RHIA and RSA do not occur in elite
      women's soccer competition. However, players increase the amount of low-intensity
      recovery undertaken between RHIA and RSA efforts, most likely in an attempt to
      maintain RHIA and RSA performance. These findings emphasize the importance of RSA
      and RHIA to elite women's soccer and highlight the importance of training this
      quality to prevent reductions in performance during competitive match play.

PMID- 22868238
TI  - Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon
      cancer.
AB  - BACKGROUND: Stage for stage, rectal cancer has historically been associated with
      inferior survival compared with colon cancer. Randomized trials of rectal cancer
      have generally demonstrated improvements in locoregional relapse but not
      survival. OBJECTIVE: We compared therapy and outcomes of colon versus rectal
      cancer in 2 time cohorts to determine if relative improvements have occurred.
      PATIENTS AND METHODS: Patients with resected stage II/III colorectal cancer
      referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were
      identified. The higher of clinical or pathologic stage was used for patients
      receiving preoperative chemoradiation. Disease-specific survival (DSS) and
      overall survival (OS) were compared for rectal and colon cancer between the 2
      cohorts. Kaplan-Meier method was used for survival analysis. RESULTS: A total of
      1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002.
      Between 1989/1990 and 2001/2002 there were significant increases in the use of
      perioperative chemotherapy for both rectal and colon cancer (P<0.001) and use of
      preoperative radiation therapy (P<0.001) and total mesorectal excision (P<0.001)
      in rectal cancer. DSS significantly improved for rectal (P<0.001) but not colon
      cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon
      cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon
      cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). CONCLUSIONS: Advances in
      locoregional and systemic therapy significantly improved survival among patients
      with rectal cancer. DSS and OS are now similar between colon and rectal cancer
      for both stage II and III disease.

PMID- 22868239
TI  - Long-term follow-up and pattern of failure for T1-T2 glottic cancer after
      definitive radiation therapy.
AB  - PURPOSE: To evaluate the impact of radiation therapy (RT) on the long-term
      outcomes and pattern of failure for T1-2 glottic cancer. MATERIALS AND METHODS:
      This is a single-institution, retrospective study. From January (1997 to 2010),
      253 patients with early glottic cancer underwent RT by 2-dimensional or 3
      dimensional RT with Co or linear accelerator. Appropriate daily bolus was applied
      with linear accelerator-based RT to avoid under dosage of the anterior
      commissure. RESULTS: A total of 253 patients with T1-T2 glottic cancer were
      treated with definitive RT. The median age was 65 and males made up 87% of the
      population. T1 was 77% of the population. The median dose and fraction size were
      63 and 2.25 Gy, respectively. After a median follow-up of 83 months, the
      locoregional control (LRC) for the whole cohort was 98%. Specifically, LRCs for
      T1 (195 patients) and T2 (58 patients) were 99.5% and 91%, respectively. Kaplan
      Meier curve shows the 5-year cause-specific survival to be 100%. CONCLUSIONS:
      Single-modality RT provides an excellent and effective treatment for T1-T2
      glottic cancer with remarkable functional preservation and 5-year LRC of 98% with
      negligible long-term toxicity.

PMID- 22868241
TI  - Is there a cause-specific survival benefit of postmastectomy radiation therapy in
      women younger than age 50 with T3N0 invasive breast cancer? A SEER database
      analysis: outcomes by receptor status/race/age: analysis using the NCI
      Surveillance, Epidemiology, and End Results (SEER) database.
AB  - OBJECTIVE: Postmastectomy radiation therapy (PMRT) remains controversial for
      patients with pathologic stage T3N0 (pT3N0) breast cancer. A Surveillance,
      Epidemiology, and End Results (SEER) database analysis suggested that PMRT might
      benefit patients older than age 50. However, the relevance between estrogen
      receptor (ER), progesterone receptor (PR), race, and PMRT in patients younger
      than age 50 is unknown. METHODS: The impact of PMRT treatment on cause-specific
      survival (CSS) and overall survival (OS) were analyzed for women in the SEER
      database from 1998 to 2007. Approximately half (47%) of the 1104 patients who met
      the study requirements received PMRT. We performed univariate analysis to compare
      CSS between the PMRT and no-PMRT groups for all patients and further stratified
      by age, race, tumor size, tumor grade, and ER/PR status. RESULTS: No difference
      in CSS or OS was detected between women treated with or without PMRT. Black/other
      race, ER-, and PR-, all suggested a trend toward decreased CSS. In univariate
      analysis, PMRT seems to be beneficial in patients younger than age 40 (hazard
      ratio=0.65; P=0.25; a nonsignificant trend in favor of PMRT). CONCLUSIONS: This
      SEER database analysis of patients younger than age 50 and with pT3N0 breast
      cancer showed that PMRT did not significantly affect CSS at 5 years; however, it
      implied a trend of benefit for patients younger than 40. The findings that
      patients with African heritage and negative ER/PR status showing decreased CSS
      warrant further investigation to determine the role of personalized PMRT in these
      high-risk cohorts.

PMID- 22868240
TI  - A Phase II trial of docetaxel and carboplatin administered every 2 weeks as
      preoperative therapy for stage II or III breast cancer: NCCTG study N0338.
AB  - OBJECTIVE: We conducted a multicenter phase II trial to assess the efficacy and
      toxicity of docetaxel and carboplatin combination as neoadjuvant therapy for
      stage II or III breast cancer (BC). METHODS: Patients received 75 mg/m of
      docetaxel and AUC 6 of carboplatin on day 1 followed by pegfilgrastim on day 2,
      every 14 days for 4 cycles, followed by definitive breast surgery. The primary
      endpoint was the proportion of patients achieving pathologic complete remission
      (pCR), defined as disappearance of all invasive and in situ tumors in the breast
      and axilla after chemotherapy. RESULTS: A total of 57 women (median age, 53 y)
      were enrolled. Thirty-eight (67%) had ER+, 31 (54%) PR+, and 6 (11%) HER2+
      disease; 9 had triple negative BC (TNBC). Forty-three (75%; 95% confidence
      interval, 62%-86%) of 57 eligible patients had clinical response (15 clinical
      complete response, 28 clinical partial response). Nine (16%; 90% confidence
      interval, 10%-28%) patients achieved pCR. Four of 9 (44%) patients with TNBC
      achieved pCR. Thrombocytopenia (5%) was the only grade 4 adverse event. The most
      common grade 3 adverse events were thrombocytopenia (19%), fatigue (12%), and
      anemia (9%). CONCLUSIONS: Four cycles of 2-weekly Docetaxel and Carboplatin are
      feasible with acceptable toxicity and a pCR rate of 16%. This regimen can be
      considered for neoadjuvant therapy of BC, particularly for patients not eligible
      for anthracycline therapy. A high pCR rate of 44% noted in a subset of patients
      with TNBC is encouraging and needs to be validated in large prospective trials.

PMID- 22868242
TI  - Stereotactic body radiotherapy for the treatment of oligometastatic renal cell
      carcinoma.
AB  - OBJECTIVES: Renal cell carcinoma (RCC) is considered radioresistant, but
      stereotactic radiosurgery can control intracranial metastases. Advances in
      radiotherapy, such as stereotactic body radiotherapy (SBRT), allow high-dose
      radiation delivery to extracranial sites. Herein, we report our experience
      treating oligometastatic RCC with SBRT. METHODS: Patients with RCC and limited
      metastases were treated on a 3-fraction dose-escalation protocol (8 to 14
      Gy/fraction) or off protocol with 10 fractions (4 to 5 Gy/fraction). Disease
      control was evaluated with serial imaging, and the Kaplan-Meier method was used
      to estimate lesion control (LeC), distant control, and survival. RESULTS:
      Eighteen consecutively treated patients with 39 metastases were treated using
      SBRT; 12 underwent treatment for all metastatic sites. Median follow-up was 16.2
      months. Treatment was well tolerated; the most common acute toxicity was fatigue
      (61.1%) and late toxicity was limited. At 2 years, LeC was 91.4% and overall
      survival was 85%. Those who underwent treatment for all metastatic sites had a 2
      year LeC of 100% and distant control of 35.7%. A shorter interval from diagnosis
      to SBRT predicted for distant progression. Freedom from any post-SBRT therapy was
      64.2% at 1 year. CONCLUSIONS: In metastatic RCC, SBRT produces promising LeC with
      minimal toxicity. Further study should be expanded beyond that of managing
      intracranial disease. Its selected use may delay the requirement for systemic
      therapies.

PMID- 22868243
TI  - Randomized phase II study of capecitabine with or without oxaliplatin as first
      line treatment for elderly or fragile patients with metastatic colorectal cancer:
      a prospective, multicenter trial of the Korean Cancer Study Group CO06-01.
AB  - BACKGROUND: To compare 2 different strategies of chemotherapy for elderly
      metastatic colorectal cancer patients. METHODS: This randomized, multicenter
      phase II study involved 80 metastatic colorectal cancer patients aged 70 years
      and above (performance status [PS] 0-2) or 65 years and above (PS 2), randomly
      assigned to arm A (capecitabine 1250 mg/m twice daily on days 1-14) or arm B
      (capecitabine 1000 mg/m twice daily on days 1-14, oxaliplatin 100 mg/m on day 1
      initially, 130 mg/m for subsequent cycles). Primary endpoint was response rate,
      and secondary endpoints were toxicity, progression-free survival, overall
      survival, and quality of life (QoL), which was assessed with the EORTC QLQ-C30
      questionnaire. RESULTS: Confirmed response rates were 22.5% and 35.0% (P=0.217),
      progression-free survival were 4.4 and 6.6 months (P=0.335), and overall survival
      were 14.2 and 11.0 months (P=0.106). Hematologic toxicities were frequently
      observed in arm B, but grade >=3 toxicities were not different. Patients in arm A
      tended to present more favorable preservation of QoL in global health status,
      physical and role functioning, fatigue, and appetite loss. CONCLUSIONS: Initial
      aggressive treatment strategy would not be recommended for this patient
      population because QoL appeared more preserved, treatments were better tolerated,
      and survivals did not differ in patients treated with initial capecitabine
      monotherapy.

PMID- 22868244
TI  - Multimodality therapy including surgical resection and intraoperative electron
      radiotherapy for recurrent or advanced primary carcinoma of the urinary bladder
      or ureter.
AB  - OBJECTIVES: To report outcomes of multimodality therapy incorporating surgical
      resection and intraoperative electron radiotherapy (IOERT) for patients with
      locoregionally (LR) recurrent or advanced primary urothelial carcinoma. METHODS:
      From 1983 to 2009, 17 patients, consisting of 11 with LR recurrence after
      cystectomy for bladder carcinoma, 4 with LR recurrence after nephroureterectomy
      for ureteral carcinoma, and 2 with advanced primary bladder carcinoma were
      treated with multimodality therapy. In 8 patients with LR recurrence, the
      multimodality treatment was a second salvage attempt. Sixteen patients received
      perioperative external beam radiotherapy (median dose, 50.4 Gy; range, 21.6 to 60
      Gy). Extent of resection was R0 (n=7), R1 (n=1), and R2 (n=9). The median IOERT
      dose was 12.5 Gy (range, 10 to 20 Gy). Overall survival (OS) and relapse patterns
      were determined from the date of resection and IOERT using the Kaplan-Meier
      method. RESULTS: The median follow-up for surviving patients was 3.6 years
      (range, 1.1 to 10 y). OS at 1, 2, and 5 years was 53%, 31%, and 16%,
      respectively. Central (within the IOERT field), LR (tumor bed or regional lymph
      nodes), and distant relapses at 2 years were 15%, 49%, and 67%, respectively. On
      univariate analysis, resection of all gross disease (R0-1) was associated with
      improved OS (P=0.03). Mortality within 30 days was 0%. Two patients (12%)
      experienced NCI-CTCAE grades 4 and 5 late adverse events. CONCLUSIONS: In
      patients with recurrent or advanced urothelial carcinoma, this multimodality
      approach yielded a low rate of recurrence within the IOERT field with acceptable
      toxicity. However, LR and distant relapse were common, indicating a need for
      better patient selection, LR therapy, and systemic therapy.

PMID- 22868245
TI  - Efficacy and safety of docetaxel combined with oxaliplatin as a neoadjuvant
      chemotherapy regimen for Chinese triple-negative local advanced breast cancer
      patients. A prospective, open, and unicentric Phase II clinical trial.
AB  - BACKGROUND AND AIMS: To determine the efficacy and toxicity of an oxaliplatin
      based regimen as a neoadjuvant chemotherapy setting in triple-negative local
      advanced breast cancer (TNLABC) patients. METHODS: Patients with stage IIIb or
      IIIc, chemotherapy-naive TNLABC receive docetaxel 75 mg/m day 1 and oxaliplatin
      130 mg/m day 2, every 21 days for up to 4 cycles. The primary end point is
      pathologic complete response (CR), and the secondary end points are clinical
      response (including CR and partial response), disease-free survival, overall
      survival, and safety. RESULTS: Twenty-nine TNLABC patients were treated:
      17(58.62%) had stage IIIB disease and 12 (41.38%) had stage IIIC disease. After
      neoadjuvant chemotherapy, there were 10 patients (34.48%) with pathologic CR (95%
      confidence interval, 21.51%-48.70%). Twenty patients responded (7 CR and 13
      partial response) with a 68.97% total clinical response rate (95% confidence
      interval 57.51%-88.02%). Nearly 27.59% patients (8 patients) had disease
      progression after at least 2 cycles of chemotherapy, and only 1 patient (3.45%)
      had the disease stable, respectively. In the 29 treated patients, there were no
      unusual or unexpected adverse events in a total of 91 cycles for the chemotherapy
      setting. Common grade 3 or 4 hematologic toxicities were leukocytopenia, which
      occurred in 4 TNLABC patients (13.79%), and thrombocytopenia in 1 patient
      (3.45%). Grade 3 or 4 transaminase elevation occurred in 5 (17.24%) patients and
      grade 3 vomiting occurred in 1(3.45%) patient. One patient experienced grade 3
      neurosensory toxicities. There are 5 reports (17.24%) of grade 3 fatigue.
      CONCLUSIONS: The results of this phase II clinical study suggest that docetaxel
      combined with oxaliplatin as a neoadjuvant chemotherapy regimen in TNLABC
      patients is active and well tolerated, and should be further investigated as a
      favorable treatment alternative for TNLABC patients. A large randomized
      prospective clinical study is warranted to confirm the results.

PMID- 22868246
TI  - State-of-the-art management of renal cell carcinoma.
AB  - In the United States, renal cell cancer (RCC) is the third most common
      genitourinary tumor and the seventh most common cancer. Standard treatment of the
      primary tumor in RCC is complete resection by either a radical or partial
      nephrectomy which can be done as an open procedure or laparoscopically. Given the
      increasing incidence in the diagnosis of early-stage RCC and the toxicity and
      invasiveness associated with surgery, less invasive options (eg, radiofrequency
      ablation) have been used recently as an alternative. Although conventional
      radiotherapy plays a role in the palliative setting, its role is otherwise
      limited. This is partly because of the in vitro and clinical data showing that
      RCC is relatively radioresistant to radiotherapy. The advances in immobilization
      and image guidance have led several investigators to consider stereotactic
      techniques to overcome this resistance with impressive results in the metastatic
      setting. Recent retrospective and prospective phase II trials of RCC stereotactic
      body radiotherapy have shown excellent local controls up to 90% to 98%. Given
      these results and the noninvasive nature of stereotactic body radiotherapy this
      modality should be further evaluated as a treatment of choice for the primary RCC
      tumor. Although RCC is also resistant of conventional chemotherapy agents,
      exciting recent advances have emerged in the treatment of systemic disease with
      the development of targeted agents in addition to immunotherapy-based treatments.
      In the current critical review we discuss these emerging trends in localized and
      systemic treatment as well as possible interesting combinations of the 2
      modalities. 

PMID- 22868247
TI  - Intermittent LHRH therapy in the management of castrate-resistant prostate cancer
      (CRPCa): results of a multi-institutional randomized prospective clinical trial.
AB  - BACKGROUND: Patients who develop castration-resistant prostate cancer (CRPCa)
      typically continue on androgen deprivation therapy (ADT). Whether these patients
      need to remain on ADT has not been well studied. We conducted a multicenter
      randomized trial to compare an intermittent versus continuous approach to ADT in
      CRPCa patients. Overall survival, health-related quality of life (QOL), and cost
      were the main endpoints. METHODS: CRPCa patients were randomized 2:1 to
      intermittent or continuous luteinizing hormone-releasing hormone agonists
      (LHRHa). Patients were followed with clinical assessments, laboratory
      investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2
      months. If the serum testosterone rose above castrate levels (1.75 nmol/L), LHRHa
      were reinitiated. The study was designed to close if >50% of patients needed to
      restart ADT in the intermittent arm. RESULTS: Thirty-one patients were followed
      with a median follow-up of 26.8 months-18 in the intermittent arm and 13 in the
      continuous. Twelve of 18 patients on the intermittent arm were reinitiated on
      LHRHa at a median time of 17.9 months. There was no difference in overall or
      cancer-specific survival between the 2 arms. There was no statistically
      significant difference in QOL between the 2 arms at 0 and 12 months. The total
      mean costs at 24 months were significantly lower in the intermittent arm ($3135
      vs. $8253 Canadian dollars, P=0.0167) compared with the continuous. The main
      limitation of this study is the small sample size. CONCLUSIONS: We have observed
      that intermittent ADT in patients with CRPCa, using a testosterone of >1.75
      ngmol/L as a trigger to reinitiate LHRHa, results in a substantial cost savings
      with no negative impact on oncologic and QOL outcomes.

PMID- 22868248
TI  - Conceptualization of sexual partner relationship steadiness among ethnic minority
      adolescent women: implications for evidence-based behavioral sexual risk
      reduction interventions.
AB  - Cognitive behavioral interventions for sexual risk reduction have been less
      successful among ethnic minority adolescent women with histories of abuse and
      sexually transmitted infections (STI) than among other adolescent populations.
      African American and Mexican American adolescent women (ages 14-18 years, n =
      548) self-reported sexual partner relationship steadiness and sexual risk
      behaviors via semi-structured interviews at study entry. Descriptive and
      bivariate analyses compared sexual risk behaviors by sexual partner relationship
      steadiness. Steady and unsteady relationships were conceptualized differently.
      Steady relationships included emotional or financial support, sexual
      communication, greater relationship importance, unintended pregnancy, and
      perceived monogamy during break-ups. Unsteady relationships were unpredictable,
      including sex with ex-steady partners and friends with benefits, lack of mutual
      respect, and poor sexual communication. Modification of sexual risk reduction
      interventions including conceptualizations of risk by context of sexual partner
      relationship status is recommended to enhance efficacy among minority adolescent
      women with STI or history of abuse.

PMID- 22868249
TI  - Road user behaviour changes following a self-explaining roads intervention.
AB  - The self-explaining roads (SER) approach uses road designs that evoke correct
      expectations and driving behaviours from road users to create a safe and user
      friendly road network. Following the implementation of an SER process and
      retrofitting of local and collector roads in a suburb within Auckland City, lower
      speeds on local roads and less variation in speed on both local and collector
      roads were achieved, along with a closer match between actual and perceived safe
      speeds. Preliminary analyses of crash data shows that the project has resulted in
      a 30% reduction crash numbers and an 86% reduction in crash costs per annum,
      since the road changes were completed. In order to further understand the
      outcomes from this project, a study was carried out to measure the effects of the
      SER intervention on the activity and behaviour of all road users. Video was
      collected over nine separate days, at nine different locations, both before and
      after SER construction. Road user behaviour categories were developed for all
      potential road users at different location types and then used to code the video
      data. Following SER construction, on local roads there was a relatively higher
      proportion of pedestrians, less uniformity in vehicle lane keeping and less
      indicating by motorists along with less through traffic, reflecting a more
      informal/low speed local road environment. Pedestrians were less constrained on
      local roads following SER construction, possibly reflecting a perceptually safer
      and more user-friendly environment. These behaviours were not generally evident
      on collector roads, a trend also shown by the previous study of speed changes.
      Given that one of the objectives of SER is to match road user behaviour with
      functionally different road categories, the road user behaviour differences
      demonstrated on different road types within the SER trial area provides further
      reinforcement of a successful SER trial.

PMID- 22868250
TI  - Ureteral stenting in cytoreductive surgery plus hyperthermic intraperitoneal
      chemotherapy as a routine procedure: evidence and necessity.
AB  - INTRODUCTION: There is a need for more exhaustive data concerning the use of
      prophylactic ureteral stenting for extended debulking and cytoreductive
      procedures in the literature. MATERIAL AND METHODS: A retrospective analysis of
      the CARPEPACEM study protocol database was performed. The trial protocol
      schedules the positioning of bilateral ureteral stents before cytoreductive
      surgery + hyperthermic intraperitoneal chemotherapy (HIPEC). RESULTS: Fifty-one
      operated patients: 31 (59.6%) with peritoneal dissemination from ovarian cancer,
      8 (15.3%) from colorectal cancer, 4 (7.9%) from pseudomyxoma peritonei, 3 (5.7%)
      from gastric cancer, 2 (3.8%) from peritoneal mesothelioma, 1 (1.9%) from
      appendiceal cancer, 1 (1.9%) from endometrial cancer, and 1 (1.9%) from
      leiomyosarcoma. Mean and median peritoneal cancer index: 11 and 10 (range: 0-28).
      CC-score: CC-0 in 45 (86.5%) patients, CC-1 in 5 (9.6%) and CC-2 in 1 (1.9%).
      HIPEC was performed with platinum + taxol in 22 patients (42.3%), platinum +
      adriablastin in 10 (19.2%), mitomycin in 9 (17.3%), platinum + mitomycin in 7
      (13.4%), platinum + doxorubicin in 2 (3.8%), and taxol + adriablastin in 1
      (1.9%). Two major ureteral complications were observed (3.9%). DISCUSSION:
      Prophylactic ureteral stenting could reduce the risk of postoperative ureteral
      complications without an increase in stent placement-related complications;
      however, a randomized clinical trial is needed.

PMID- 22868251
TI  - Alterations of the serum peptidome in renal cell carcinoma discriminating benign
      and malignant kidney tumors.
AB  - Renal cell carcinoma (RCC) is typically asymptomatic and surgery usually
      increases patient's life only for early stage tumors. However, some cystic and
      solid renal lesions cannot be confidently differentiated from clear-cell-RCC.
      Therefore possible markers for early detection and to distinguish malignant
      kidney tumors are needed. To this aim, we applied MALDI-TOF and LC-MS/MS analysis
      to RPC18 MB purified serum of ccRCC, non-ccRCC patients and controls. A cluster
      of five signals differentiate malignant tumors from benign renal masses and
      healthy subjects. Moreover, a combination of six ions showed the highest
      specificity and sensitivity to distinguish ccRCC from controls. Healthy subjects
      were also differentiated from non-ccRCC by three features. Peptide ratios
      obtained by MALDI-TOF were compared with those from label-free LC-ESI and no
      statistical difference was found (p>0.05). ESI-results were linked with MALDI
      profiles by both TOF/TOF sequencing and MALDI FT-ICR accurate mass measurements.
      About 200 unique endogenous peptides, originating from 32 proteins, were
      identified. Among them, SDPR and ZYX were found down-expressed, while SRGN and
      TMSL3 were up-expressed. In conclusion, our results suggest the possibility to
      discriminate malignant kidney tumors based on a cluster of serum peptides.
      Moreover, label-free approach may represent a valid method to verify results
      obtained by MALDI-TOF. This article is part of a Special Issue entitled:
      Integrated omics.

PMID- 22868252
TI  - Shotgun proteome analysis of beer and the immunogenic potential of beer
      polypeptides.
AB  - The majority of beer proteins originate from barley (Hordeum vulgare) which is
      used for brewing. Barley is known to contain celiacogenic gliadin-like prolamins
      (hordeins) along with other immunogenic proteins which endure malt proteases and
      the harsh conditions of brewing. In addition, a multitude of peptides that may
      retain or even amplify the immune-stimulating potential is released in beer
      because of proteolysis. The comprehensive annotation of the beer proteome is
      challenged both by the high concentration range of the protein entities and by a
      severe degree of processing-induced modifications. Overcoming the pitfalls of the
      classical two-dimensional electrophoresis approach coupled to mass spectrometry
      (MS), the gel-free shotgun proteomic analysis expanded the current inventory of a
      popular Italian beer to 33 gene products, including traces of intact B- and D
      hordeins and 10 proteins from Saccharomyces spp. The high performance liquid
      chromatography-electrospray MS/MS peptidomic analysis of the low-molecular weight
      beer components disclosed a panel of hordein-derived peptides that encrypt gluten
      like sequence motifs, potentially harmful to celiacs. The presence of antigliadin
      IgA-immunoresponsive prolamins was assayed by Western and dot blot using sera of
      N=4 celiac patients. Gliadin-reactive T-cell lines isolated from the intestine of
      N=5 celiacs activated an IFN-gamma response when challenged with deamidated beer
      polypeptides.

PMID- 22868253
TI  - Factors associated with physician and nurse practitioner pressure ulcer staging
      practices in rehabilitative and long term care.
AB  - Pressure ulcer (PrU) documentation is a common clinical challenge in long term
      care and rehabilitative settings. This pilot observational study examined PrU
      staging documentation practices by physicians and nurse providers in two long
      term care facilities with short-term rehabilitative units. The study enrolled 57
      subjects with PrUs, and only 30 (52.6%) of them had PrU staging documentation by
      the physician or nurse practitioner. Use of powered mattresses (adjusted relative
      risk (RR) 2.43 with 95% CI 1.19, 4.97) and physical therapy documentation (RR
      1.72 with 95% CI 1.04, 2.81) were factors significantly associated with providers
      documenting the PrU stage. Inadequate statistical power, due to the small study
      sample size, may have prevented detecting of other significant associations
      between patient factors and documentation practices. Future research that is
      adequately powered is needed to replicate these results and detect other
      potential factors associated with documentation.

PMID- 22868254
TI  - Combination of TNF-alpha, homocysteine and adenosine exacerbated cytotoxicity in
      human cardiovascular and cerebrovascular endothelial cells.
AB  - Disruption to the vascular homoeostasis is detrimental in vascular diseases. This
      study examined how the combination of homocysteine, adenosine and tumor necrosis
      factor-alpha (TNF-alpha) influenced endothelial cell survival. In cultured human
      derived cardiovascular (EA.hy926) and cerebrovascular (HBEC-5i) endothelial
      cells, cell death events were initiated by TNF-alpha (0.1-10 ng/mL) only when
      both homocysteine (0.5 mM) and adenosine (0.5 mM) were present. The accelerated
      cell death events induced by the combination were triggered through excessive
      apoptosis. This was evident by membrane phospholipid phosphatidylserine
      externalisation, cell shrinkage and DNA fragmentation, as well as an increase in
      the expressions and occurrence of active caspase-3 and cleaved poly(ADP-ribose)
      polymerase (PARP) positive cells. Collectively, homocysteine, adenosine and TNF
      alpha are interrelated in the survival of endothelial cells, and this co
      existence should be considered in future drug development for cardiovascular and
      cerebrovascular diseases.

PMID- 22868255
TI  - A structural investigation of the alkali metal site distribution within bioactive
      glass using neutron diffraction and multinuclear solid state NMR.
AB  - The atomic-scale structure of Bioglass and the effect of substituting lithium for
      sodium within these glasses have been investigated using neutron diffraction and
      solid state magic angle spinning (MAS) NMR. Applying an effective isomorphic
      substitution difference function to the neutron diffraction data has enabled the
      Na-O and Li-O nearest-neighbour correlations to be isolated from the overlapping
      Ca-O, O-(P)-O and O-(Si)-O correlations. These results reveal that Na and Li
      behave in a similar manner within the glassy matrix and do not disrupt the short
      range order of the network former. Residual differences are attributed solely to
      the variation in ionic radius between the two species. Successful simplification
      of the 2 < r (A) < 3 region via the difference method has enabled all the nearest
      neighbour correlations to be deconvolved. The diffraction data provides the first
      direct experimental evidence of split Na-O nearest-neighbour correlations in
      these melt quench bioactive glasses, and an analogous splitting of the Li-O
      correlations. The observed correlations are attributed to the metal ions bonded
      either to bridging or to non-bridging oxygen atoms. (23)Na triple quantum MAS
      (3QMAS) NMR data corroborates the split Na-O correlations. The structural sites
      present will be intimately related to the release properties of the glass system
      in physiological fluids such as plasma and saliva, and hence to the bioactivity
      of the material. Detailed structural knowledge is therefore a prerequisite for
      optimizing material design.

PMID- 22868257
TI  - Consistency of pacing and metabolic responses during 2000-m rowing ergometry.
AB  - PURPOSE: This study investigated the pacing strategy adopted and the consistency
      of performance and related physiological parameters across three 2000-m rowing
      ergometer tests. METHODS: Fourteen male well-trained rowers took part in the
      study. Each participant performed three 2000-m rowing-ergometer tests
      interspersed by 3-7 d. Throughout the trials, respiratory exchange and heart rate
      were recorded and power output and stroke rate were analyzed over each 500 m of
      the test. At the completion of the trial, assessments of blood lactate and rating
      of perceived exertion were measured. RESULTS: Ergometer performance was unchanged
      across the 3 trials; however, pacing strategy changed from trial 1, which
      featured a higher starting power output and more progressive decrease in power,
      to trials 2 and 3, which were characterized by a more conservative start and an
      end spurt with increased power output during the final 500 m. Mean typical error
      (TE; %) across the three 2000-m trials was 2.4%, and variability was low to
      moderate for all assessed physiological variables (TE range = 1.4-5.1%) with the
      exception of peak lactate (TE = 11.5%). CONCLUSIONS: Performance and
      physiological responses during 2000-m rowing ergometry were found to be
      consistent over 3 trials. The variations observed in pacing strategy between
      trial 1 and trials 2 and 3 suggest that a habituation trial is required before an
      intervention study and that participants move from a positive to a reverse-J
      shaped strategy, which may partly explain conflicting reports in the pacing
      strategy exhibited during 2000-m rowing-ergometer trials.

PMID- 22868256
TI  - A prospective validation pharmacogenomic study in the adjuvant setting of
      colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin
      (FOLFOX4) regimen.
AB  - The discovery of pharmacogenomic markers in colorectal cancer (CRC) could be
      setting-specific. FOLFOX4 is employed in the adjuvant and metastatic setting in
      CRC. This prospective study is aimed to validate in the adjuvant setting the
      pharmacogenomic markers of toxicity reported in the metastatic setting (that is,
      GSTP1-rs947894, and -rs1138272; GSTM1-null genotype; AGXT-rs4426527, -rs34116584
      and del-74 bp), and to discover additional markers. CRC patients (n=144) treated
      with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes. Grade >= 2
      neurotoxicity was associated (false discovery rate-adjusted q-value <0.1) with
      single-nucleotide polymorphisms in ABCC1 (rs2074087: odds ratio=0.43(0.22-0.86)),
      and ABCC2 (rs3740066: 2.99(1.16-7.70); rs1885301: 3.06(1.35-6.92); rs4148396:
      4.69(1.60-13.74); rs717620: 14.39(1.63-127.02)). hMSH6-rs3136228 was associated
      with grade 3-4 neutropenia (3.23(1.38-7.57), q-value=0.0937). XRCC3-rs1799794 was
      associated with grade 3-4 non-hematological toxicity (8.90(2.48-31.97), q
      value=0.0150). The markers previously identified in metastatic CRC were not
      validated. We have identified new markers of toxicity in genes of transport and
      DNA repair. If validated in other studies, they could help to identify patients
      at risk of toxicity.

PMID- 22868258
TI  - Heat management strategies for solid-state NMR of functional proteins.
AB  - Modern solid-state NMR methods can acquire high-resolution protein spectra for
      structure determination. However, these methods use rapid sample spinning and
      intense decoupling fields that can heat and denature the protein being studied.
      Here we present a strategy to avoid destroying valuable samples. We advocate
      first creating a sacrificial sample, which contains unlabeled protein (or no
      protein) in buffer conditions similar to the intended sample. This sample is then
      doped with the chemical shift thermometer Sm2Sn2O7. We introduce a pulse scheme
      called TCUP (for Temperature Calibration Under Pulseload) that can characterize
      the heating of this sacrificial sample rapidly, under a variety of experimental
      conditions, and with high temporal resolution. Sample heating is discussed with
      respect to different instrumental variables such as spinning speed, decoupling
      strength and duration, and cooling gas flow rate. The effects of different sample
      preparation variables are also discussed, including ionic strength, the inclusion
      of cryoprotectants, and the physical state of the sample (i.e. liquid, solid, or
      slurry). Lastly, we discuss probe detuning as a measure of sample thawing that
      does not require retuning the probe or using chemical shift thermometer
      compounds. Use of detuning tests and chemical shift thermometers with
      representative sample conditions makes it possible to maximize the efficiency of
      the NMR experiment while retaining a functional sample.

PMID- 22868260
TI  - Molecular epidemiological analysis of methicillin-resistant Staphylococcus aureus
      isolates from a medical intensive care unit: a comparison of nasal and clinical
      isolates.
AB  - BACKGROUND: The control of nosocomial transmission of methicillin-resistant
      Staphylococcus aureus (MRSA) represents a significant challenge to infection
      control professionals. Nasal carriage colonization by MRSA plays a crucial role
      in the epidemiology and pathogenesis of this infection. METHODS: Patients in the
      medical intensive care unit (ICU) between November 2010 and March 2011 were
      swabbed when hospitalized, reswabbed 1 week later and for a third time, when they
      were discharged from the ICU. All swabs were examined within 2 hours of
      collection using ChromID MRSA-Select agar plates to detect MRSA. Positive
      specimens were determined to have the mecA and femB gene through amplification
      with duplex polymerase chain reaction. Repetitive element sequence-based
      polymerase chain reaction was used to investigate the epidemiological types of
      MRSA isolates in the third screening and clinical isolates obtained from 2007 to
      2010 in West China Hospital. A comparison of molecular types was performed to
      investigate the genetic relationship between nasal and clinical isolates.
      RESULTS: After the third screening, 16 nasal MRSA isolates were identified.
      Epidemiological analysis revealed that 16 nasal MRSA isolates and 37 clinical
      MRSA isolates differentiated into 2 clusters, comprising 9 subclusters. Of the 16
      nasal strains, 11 (68.8%) belonged to subcluster I of cluster I; 3 of 9
      subclusters consisted of both nasal and clinical isolates, while 4 of 9
      subclusters consisted of clinical isolates and only 2 of 9 consisted of nasal
      isolates. CONCLUSIONS: Our study indicated a high degree of genetic relatedness
      between nasal and clinical MRSA isolates. The molecular typing of MRSA is
      critical for controlling the nosocomial transmission of this pathogen in ICU
      setting and defining a nosocomial infection control policy.

PMID- 22868261
TI  - Charmed with a name.

PMID- 22868262
TI  - Cancer genomics: chromatin influence on cancer mutation rate.

PMID- 22868263
TI  - Transforming clinical microbiology with bacterial genome sequencing.
AB  - Whole-genome sequencing of bacteria has recently emerged as a cost-effective and
      convenient approach for addressing many microbiological questions. Here, we
      review the current status of clinical microbiology and how it has already begun
      to be transformed by using next-generation sequencing. We focus on three
      essential tasks: identifying the species of an isolate, testing its properties,
      such as resistance to antibiotics and virulence, and monitoring the emergence and
      spread of bacterial pathogens. We predict that the application of next-generation
      sequencing will soon be sufficiently fast, accurate and cheap to be used in
      routine clinical microbiology practice, where it could replace many complex
      current techniques with a single, more efficient workflow.

PMID- 22868265
TI  - Splicing: waiting to be spliced.

PMID- 22868264
TI  - Transcription factors: from enhancer binding to developmental control.
AB  - Developmental progression is driven by specific spatiotemporal domains of gene
      expression, which give rise to stereotypically patterned embryos even in the
      presence of environmental and genetic variation. Views of how transcription
      factors regulate gene expression are changing owing to recent genome-wide studies
      of transcription factor binding and RNA expression. Such studies reveal patterns
      that, at first glance, seem to contrast with the robustness of the developmental
      processes they encode. Here, we review our current knowledge of transcription
      factor function from genomic and genetic studies and discuss how different
      strategies, including extensive cooperative regulation (both direct and
      indirect), progressive priming of regulatory elements, and the integration of
      activities from multiple enhancers, confer specificity and robustness to
      transcriptional regulation during development.

PMID- 22868266
TI  - Chromatin: nucleosomal dynamics at centromeres.

PMID- 22868268
TI  - Veil nerve-sparing technique and postoperative urinary continence in open
      antegrade radical prostatectomy.
AB  - PURPOSE: To introduce and evaluate our open antegrade radical prostatectomy (ARP)
      technique, a nerve-sparing technique which offers patients better postsurgical
      urinary continence by our technique of 'Veil of Aphrodite'. METHODS: Ninety
      consecutive bilateral nerve-sparing ARPs performed using the Veil technique
      (intrafascial dissection) were compared to control ARP cases using non- or
      unilateral nerve sparing. Correlation of urinary continence with
      immunohistochemical (IHC) stains of nerves (S-100) around the prostate capsule
      was investigated in 20 consecutive patients whose ARPs were performed by a single
      surgeon. RESULTS: Fifty-one cases (56.7%) had no urinary incontinence and 72
      cases (80.0%) had no or only minor urinary leakage (less than 5% in total a day),
      and these were significantly higher than in the control group (p = 0.000 and
      0.003, respectively) without compromising the surgical margins. S-100 IHC stains
      significantly correlated nerve sparing (bilateral sparing vs. non-sparing, p =
      0.0398), urinary continence (no urinary continence vs. more than 5% in total
      urine volume a day, p = 0.0489), and early removal of catheter (within a week vs.
      over a week, p = 0.0041). CONCLUSIONS: Open nerve-sparing ARP using the Veil
      technique may offer better urinary continence postoperatively and this may be
      supported by S-100 IHC results. This method may be adaptable in any surgical
      institution.

PMID- 22868269
TI  - Trace metals, peroxidase activity, PAHs contents and ecophysiological changes in
      Quercus ilex leaves in the urban area of Caserta (Italy).
AB  - Trace metals and polycyclic aromatic hydrocarbons, severely affecting human,
      animal and plants health, highly contribute to the air pollution in urban areas
      mainly due to car traffic. In this study the air biomonitoring of the city of
      Caserta (South Italy) has been performed by using Quercus ilex L., a widespread
      ornamental plant in parks, gardens and avenues. The plant leaves from different
      sites within the urban area were collected and used to determine the
      concentrations of V, Cd, Cr, Pb, Ni, Cu, and PAHs as well as the free amino acid
      content and peroxidase enzyme activity as indices of the leaf physiological
      conditions. All the tested trace metals showed concentrations higher than the
      control site. Lead was positively correlated to Cd and Cr and showed, also, a
      positive trend with Ni and Cu that, in their turn, were highly correlated between
      them. Positive and significant correlations were evidenced between total PAHs and
      carcinogenic PAHs and negative correlations between those and all trace metals
      assayed except V. Cu and Cd contents evidence negative correlations with
      peroxidase activity, and the free amino acid contents. The PAHs, in particular
      Carc-PAHs, were negatively correlated to the tested heavy metals. POD was
      positively correlated only with V and negatively correlated with Cu and Cd.

PMID- 22868267
TI  - The Notch signalling system: recent insights into the complexity of a conserved
      pathway.
AB  - Notch signalling links the fate of one cell to that of an immediate neighbour and
      consequently controls differentiation, proliferation and apoptotic events in
      multiple metazoan tissues. Perturbations in this pathway activity have been
      linked to several human genetic disorders and cancers. Recent genome-scale
      studies in Drosophila melanogaster have revealed an extraordinarily complex
      network of genes that can affect Notch activity. This highly interconnected
      network contrasts our traditional view of the Notch pathway as a simple linear
      sequence of events. Although we now have an unprecedented insight into the way in
      which such a fundamental signalling mechanism is controlled by the genome, we are
      faced with serious challenges in analysing the underlying molecular mechanisms of
      Notch signal control.

PMID- 22868270
TI  - Selective in situ functionalization of biosensors on LOC devices using laminar co
      flow.
AB  - Many applications involving lab-on-a-chip (LOC) devices are prevented from
      entering the market because of difficulties to achieve mass production and impart
      suitable properties allowing long-term storage. To integrate biosensors on these
      microfluidic chips, one of the main restrictions is the fabrication and stability
      of the molecular modifications that must be performed on the surfaces of the
      sensors for a given application. The complexity of the problem increases
      exponentially when the LOC integrates several of these sensors. Here we present a
      system based on laminar co-flow to perform an on-chip selective surface bio
      functionalization of LOC-integrated sensors. This method has the advantage that
      the surface modification protocols are performed in situ before analyte
      detection. This approach reduces the burdens during LOC fabrication, keeping the
      required reagents stored outside of the detection structure in suitable wet
      conditions. The proof of concept is demonstrated through an optical
      characterization followed by electronic detection based on a novel differential
      impedance measurement setup. The system can be easily scaled to incorporate
      several sensors with distinct biosensing targets in a single chip.

PMID- 22868271
TI  - PGC7, H3K9me2 and Tet3: regulators of DNA methylation in zygotes.
AB  - In zygotes, a global loss of DNA methylation occurs selectively in the paternal
      pronucleus before the first cell division, concomitantly with the appearance of
      modified forms of 5-methylcytosine. The adjacent maternal pronucleus and certain
      paternally-imprinted loci are protected from this process. Nakamura et al.
      recently clarified the molecular mechanism involved: PGC7/Stella/Dppa3 binds to
      dimethylated histone 3 lysine 9 (H3K9me2), thereby blocking the activity of the
      Tet3 methylcytosine oxidase in the maternal genome as well as at certain
      imprinted loci in the paternal genome.

PMID- 22868272
TI  - Huntington's disease: dancing in a dish.
AB  - In a recent landmark paper, the Huntington's disease (HD) iPSC Consortium reports
      on the establishment and characterization of a panel of iPSC lines from HD
      patients, and more importantly, the successful modeling of HD in vitro. In the
      same issue of Cell Stem Cell, An et al. reports on the successful targeted gene
      correction of HD in human iPSCs. Both advances are exciting, provide new
      resources for current and future HD research, and uncover new challenges to
      better understand and, most importantly, treat this devastating disease in the
      near future.

PMID- 22868273
TI  - National trends in the office-based treatment of children, adolescents, and
      adults with antipsychotics.
AB  - CONTEXT Although antipsychotic treatment has recently increased, little is known
      about how this development has differentially affected the office-based care of
      adults and young people in the United States. OBJECTIVE To compare national
      trends and patterns in antipsychotic treatment of adults and youths in office
      based medical practice. DESIGN Trends between 1993 and 2009 in visits with
      antipsychotics for children (0-13 years), adolescents (14-20 years), and adults
      (>=21 years) are described on a per population basis and as a proportion of total
      medical office visits. Background and clinical characteristics of recent (2005
      2009) antipsychotic visits are also compared by patient age. SETTING Outpatient
      visits to physicians in office-based practice. PARTICIPANTS Visits from the 1993
      2009 National Ambulatory Medical Care Surveys (N = 484 889). MAIN OUTCOME
      MEASURES Visits with a prescription of antipsychotic medications. RESULTS Between
      1993-1998 and 2005-2009, visits with a prescription of antipsychotic medications
      per 100 persons increased from 0.24 to 1.83 for children, 0.78 to 3.76 for
      adolescents, and 3.25 to 6.18 for adults. The proportion of total visits that
      included a prescription of antipsychotics increased during this period from 0.16%
      to 1.07% for youths and from 0.88% to 1.73% for adults. From 2005 to 2009,
      disruptive behavior disorders were the most common diagnoses in child and
      adolescent antipsychotic visits, accounting for 63.0% and 33.7%, respectively,
      while depression (21.2%) and bipolar disorder (20.2%) were the 2 most common
      diagnoses in adult antipsychotic visits. Psychiatrists provided a larger
      proportion of the antipsychotic visits for children (67.7%) and adolescents
      (71.6%) than to adults (50.3%) (P < .001). From 2005 to 2009, antipsychotics were
      included in 28.8% of adult visits and 31.1% of youth visits to psychiatrists.
      CONCLUSIONS On a population basis, adults make considerably more medical visits
      with a prescription of antipsychotics than do adolescents or children. Yet
      antipsychotic treatment has increased especially rapidly among young people, and
      recently antipsychotics have been prescribed in approximately the same proportion
      of youth and adult visits to psychiatrists.

PMID- 22868274
TI  - Effect of a pharmacist medication review in elderly patients discharged from the
      hospital.

PMID- 22868275
TI  - Pulse oximetry and high-dose vasopressors: a comparison between forehead
      reflectance and finger transmission sensors.
AB  - PURPOSE: Pulse oximetry (SpO(2)) measured at finger site via transmission mode
      may fail in situations of hypoperfusion. Forehead sensors using reflectance
      technology might be useful in these circumstances. We hypothesized that
      reflectance SpO(2) would be more accurate than finger SpO(2) in patients with
      severe shock. METHODS: A prospective observational study was conducted in an
      intensive care unit of a university hospital of patients in shock who were
      treated with high norepinephrine and/or epinephrine doses (>=0.1 MUg kg(-1) min(
      1)). When blood gas determinations were requested, forehead SpO(2) and finger
      SpO(2) values were simultaneous recorded. Agreement between SpO(2) measurements
      with arterial saturation (SaO(2)), obtained by blood analysis with a co-oximeter,
      was assessed using the Bland-Altman method. The number of outliers, defined by
      the formula SaO(2) - SpO(2) > +/-3 %, indicated the proportion of measurements
      considered to be clinically unacceptable. RESULTS: Thirty-two patients were
      enrolled in the study. With the forehead sensor no reading failure occurred, and
      140 paired data sets (forehead SpO(2) vs. SaO(2)) were obtained. Bias and
      precision were +1.0 and +2.5 %, respectively, and the limits of agreement ranged
      from -4.0 to 6.0 %. The finger sensor failed to give a value in four cases, thus
      providing 136 paired data sets (finger SpO(2) vs. SaO(2)) for analysis. Bias and
      precision were +1.4 and +4.8 %, respectively, and the limits of agreement ranged
      from -8.0 to 10.9 %. There were 21 (15 %) outliers for the forehead sensor and 43
      (32 %) for the finger sensor (P < 0.001). CONCLUSIONS: Forehead SpO(2)
      measurements were more accurate than finger SpO(2) when compared with SaO(2) in
      critically ill patients requiring high-dose vasopressor therapy and should
      therefore be the preferred method considered.

PMID- 22868276
TI  - Adverse cardiac events during catecholamine therapy: a role for hydrocortisone?

PMID- 22868278
TI  - Nickel incorporated carbon nanotube/nanofiber composites as counter electrodes
      for dye-sensitized solar cells.
AB  - A nickel incorporated carbon nanotube/nanofiber composite (Ni-CNT-CNF) was used
      as a low cost alternative to Pt as counter electrode (CE) for dye-sensitized
      solar cells (DSCs). Measurements based on energy dispersive X-rays spectroscopy
      (EDX) showed that the majority of the composite CE was carbon at 88.49 wt%, while
      the amount of Ni nanoparticles was about 11.51 wt%. Measurements based on
      electrochemical impedance spectroscopy (EIS) showed that the charge transfer
      resistance (R(ct)) of the Ni-CNT-CNF composite electrode was 0.71 Omega cm(2),
      much lower than that of the Pt electrode (1.81 Omega cm(2)). Such a low value of
      R(ct) indicated that the Ni-CNT-CNF composite carried a higher catalytic activity
      than the traditional Pt CE. By mixing with CNTs and Ni nanoparticles, series
      resistance (R(s)) of the Ni-CNT-CNF electrode was measured as 5.96 Omega cm(2),
      which was close to the R(s) of 5.77 Omega cm(2) of the Pt electrode, despite the
      significant difference in their thicknesses: ~22 MUm for Ni-CNT-CNF composite,
      while ~40 nm for Pt film. This indicated that use of a thick layer (tens of
      microns) of Ni-CNT-CNF counter electrode does not add a significant amount of
      resistance to the total series resistance (R(s-tot)) in DSCs. The DSCs based on
      the Ni-CNT-CNF composite CEs yielded an efficiency of 7.96% with a short circuit
      current density (J(sc)) of 15.83 mA cm(-2), open circuit voltage (V(oc)) of 0.80
      V, and fill factor (FF) of 0.63, which was comparable to the device based on Pt,
      that exhibited an efficiency of 8.32% with J(sc) of 15.01 mA cm(-2), V(oc) of
      0.83, and FF of 0.67.

PMID- 22868279
TI  - Inactivation and reactivation of ribonuclease A studied by computer simulation.
AB  - The year 2011 marked the half-centenary of the publication of what came to be
      known as the Anfinsen postulate, that the tertiary structure of a folded protein
      is prescribed fully by the sequence of its constituent amino acid residues. This
      postulate has become established as a credo, and, indeed, no contradictions seem
      to have been found to date. However, the experiments that led to this postulate
      were conducted on only a single protein, bovine ribonuclease A (RNAse). We
      conduct molecular dynamics (MD) simulations on this protein with the aim of
      mimicking this experiment as well as making the methodology available for use
      with basically any protein. There have been many attempts to model denaturation
      and refolding processes of globular proteins in silico using MD, but only a few
      examples where disulphide-bond containing proteins were studied. We took the view
      that if the reductive deactivation and oxidative reactivation processes of RNAse
      could be modelled in silico, this would provide valuable insights into the
      workings of the classical Anfinsen experiment.

PMID- 22868280
TI  - Talent identification and specialization in sport: an overview of some unanswered
      questions.
AB  - The theory of deliberate practice postulates that experts are always made, not
      born. This theory translated to the youth-sport domain means that if athletes
      want to be high-level performers, they need to deliberately engage in practice
      during the specialization years, spending time wisely and always focusing on
      tasks that challenge current performance. Sport organizations in several
      countries around the world created specialized training centers where selected
      young talents practice under the supervision of experienced coaches in order to
      become professional athletes and integrate onto youth national teams. Early
      specialization and accurate observation by expert coaches or scouts remain the
      only tools to find a potential excellent athlete among a great number of
      participants. In the current study, the authors present 2 of the problems raised
      by talent search and the risks of such a search. Growth and maturation are
      important concepts to better understand the identification, selection, and
      development processes of young athletes. However, the literature suggests that
      sport-promoting strategies are being maintained despite the increased demands in
      the anthropometric characteristics of professional players and demands of actual
      professional soccer competitions. On the other hand, identifying biological
      variables that can predict performance is almost impossible.

PMID- 22868281
TI  - Higher plasma homocysteine is associated with lower vitamin B6 status in
      critically ill surgical patients.
AB  - BACKGROUND: Hyperhomocysteinemia might be at least partially due to compromised B
      vitamin status in critically ill patients and has been linked with critical
      illness. This study was conducted to examine the association between plasma
      homocysteine with B vitamins and clinical outcomes in critically ill surgical
      patients. METHODS: Thirty-two patients in the surgical intensive care unit (SICU)
      were enrolled. Disease severity (Acute Physiology and Chronic Health Evaluation
      II score), hematological values, serum and erythrocyte folate, serum vitamin B12,
      plasma, and erythrocyte pyridoxal 5'-phosphate (PLP) were determined within 24
      hours of admission and again after 7 days. RESULTS: The prevalence of
      hyperhomocysteinemia in the patients was either 46.9% (plasma homocysteine >=12
      umol/L) or 31.3% (plasma homocysteine >=15 umol/L) on day 1 in the SICU and
      increased to 62.5% (plasma homocysteine >=12 umol/L) and 37.5% (plasma
      homocysteine >=15 umol/L) on day 7 after admission to the SICU. Plasma
      homocysteine, serum folate, and vitamin B12 significantly increased by day 7,
      whereas plasma and erythrocyte PLP remained constant throughout the study. Plasma
      homocysteine was not correlated with serum folate and vitamin B12. However,
      plasma and erythrocyte PLP on day 1 were adversely associated with day 1 levels
      of plasma homocysteine after adjusting for potential confounders. Plasma
      homocysteine on day 1 or changes (Delta day 7-day 1) did not show any association
      with clinical outcomes. CONCLUSIONS: Lower plasma PLP might be a significant
      factor for increased plasma homocysteine in critically ill surgical patients. The
      association between plasma homocysteine and clinical outcomes was not found.

PMID- 22868282
TI  - The microbiota and its metabolites in colonic mucosal health and cancer risk.
AB  - Recent advances in our ability to identify and characterize the human microbiota
      have transformed our appreciation of the function of the colon from an organ
      principally involved in the reabsorption of secretory fluids to a metabolic organ
      on a par with the liver. High-throughput technology has been applied to the
      identification of specific differences in microbial DNA, allowing the
      identification of trillions of microbes belonging to more than 1000 different
      species, with a metabolic mass of approximately 1.5 kg. The close proximity of
      these microbes with the mucosa and gut lymphoid tissue helps explain why a
      balanced microbiota is likely to preserve mucosal health, whereas an unbalanced
      composition, as seen in dysbiosis, may increase the prevalence of diseases not
      only of the mucosa but also within the body due to the strong interactions with
      the gut immune system, the largest immune organ of the body. Such abnormalities
      have been pinpointed as etiological factors in a wide range of diseases,
      including autoimmune disorders, allergy, irritable bowel syndrome, inflammatory
      bowel disease, obesity, and colon cancer. Recognition of the strong potential for
      food to manipulate microbiota composition has opened up new therapeutic
      strategies against these diseases based on dietary intervention.

PMID- 22868283
TI  - Prospective randomized comparative study of low-profile balloon gastrostomy tubes
      in children.
AB  - BACKGROUND: Supplemental enteral nutrition through gastrostomy tubes is well
      established in children, but prospective studies comparing different tubes remain
      lacking in this population. The study aimed at comparing different aspects
      related to the use of low-profile balloon gastrostomy tubes in children.
      MATERIALS AND METHODS: The authors prospectively studied the use of 2 tube types-
      tube A (MIC-Key gastrostomy tube; Ballard Medical Products, Draper, UT) and tube
      B (MINI One gastrostomy tube; Applied Medical Technology, Brecksville, OH)--in a
      cohort of children in a crossover study design. Children were randomly assigned
      to 1 tube type for 4 months, followed by the other tube type for the next 4
      months. Patients were evaluated at enrollment and at 4 and 8 months, with
      monitoring phone calls at 2 and 6 months. Variables measured included caregiver
      satisfaction, tube-related complications, and device durability. RESULTS: Twenty
      one patients were included in the study. Infection rate (range, 4.8%-5.0%) and
      overall leakage rate (range, 42.9%-50.0%) were similar in both groups. Trends
      were noted with other variables measured but without statistical significance.
      These included lower rates of formula leakage and granulation tissue growth and
      higher satisfaction scores with tube B and more favorable device durability with
      tube A. CONCLUSION: Both low-profile balloon gastrostomy tubes performed well and
      had comparable caregiver satisfaction, complications, and overall device
      durability.

PMID- 22868284
TI  - Rapid calculation of protein chemical shifts using bond polarization theory and
      its application to protein structure refinement.
AB  - Although difficult to analyze, NMR chemical shifts provide detailed information
      on protein structure. We have adapted the semi-empirical bond polarization theory
      (BPT) to protein chemical shift calculation and chemical shift driven protein
      structure refinement. A new parameterization for BPT amide nitrogen chemical
      shift calculation has been derived from MP2 ab initio calculations and
      successfully evaluated using crystalline tripeptides. We computed the chemical
      shifts of the small globular protein ubiquitin, demonstrating that BPT
      calculations can match the results obtained at the DFT level of theory at very
      low computational cost. In addition to the calculation of chemical shift tensors,
      BPT allows the calculation of chemical shift gradients and consequently chemical
      shift driven geometry optimizations. We applied chemical shift driven protein
      structure refinement to the conformational analysis of a set of Trypanosoma
      brucei (the causative agent of African sleeping sickness) tryparedoxin peroxidase
      Px III structures. We found that the interaction of Px III with its reaction
      partner Tpx seems to be governed by conformational selection rather than by
      induced fit.

PMID- 22868285
TI  - Iterative operations on microdroplets and continuous monitoring of processes
      within them; determination of solubility diagrams of proteins.
AB  - We demonstrate a technique for controlling the content of multiple microdroplets
      in time. We use this system to rapidly and quantiatively determine the solubility
      diagrams of two model proteins (lysozyme and ribonuclease A).

PMID- 22868287
TI  - Multiferroic nanoscale Bi2FeCrO6 material for spintronic-related applications.
AB  - We report the control of the growth mode of Bi(2)FeCrO(6) thin and ultrathin
      films by either tuning the pulsed laser deposition parameters or by using a
      buffer layer. The films are epitaxial and the heterostructures exhibit very
      smooth interfaces, thus eliminating the main obstacle in the realization of
      tunnel junctions. By characterizing the functional properties of thin films we
      find that Bi(2)FeCrO(6) retains its room temperature multiferroic character even
      at the nanoscale. The coexistence of these properties in ultra-thin Bi(2)FeCrO(6)
      films will pave the way to design multifunctional devices for applications in
      spintronics and electronics, such as ferroelectric tunnel junctions or magnetic
      tunnel junctions with ferroelectric barriers.

PMID- 22868288
TI  - Map on predicted deposition of Cs-137 in Spanish soils from geostatistical
      analyses.
AB  - The knowledge of the distribution of (137)Cs deposition over Spanish mainland
      soils along with the geographical, physical and morphological terrain information
      enable us to know the (137)Cs background content in soil. This could be useful as
      a tool in a hypothetical situation of an accident involving a radioactive
      discharge or in soil erosion studies. A Geographic Information System (GIS) would
      allow the gathering of all the mentioned information. In this work, gamma
      measurements of (137)Cs on 34 Spanish mainland soils, rainfall data taken from
      778 weather stations, soil types and geographical and physical terrain
      information were input into a GIS. Geostatistical techniques were applied to
      interpolate values of (137)Cs activity at unsampled places, obtaining prediction
      maps of (137)Cs deposition. Up to now, geostatistical methods have been used to
      model spatial continuity of data. Through semivariance and cross-covariance
      functions the spatial correlation of such data can be studied and described.
      Ordinary and simple kriging techniques were carried out to map spatial patterns
      of (137)Cs deposition, and ordinary and simple co-kriging were used to improve
      the prediction map obtained through a second related variable: namely the
      rainfall. To choose the best prediction map of (137)Cs deposition, the spatial
      dependence of the variable, the correlation coefficient and the prediction errors
      were evaluated using the different models previously mentioned. The best result
      for (137)Cs deposition map was obtained when applying the co-kriging techniques.

PMID- 22868289
TI  - The effect of music on 10-km cycle time-trial performance.
AB  - Music is widely used as an ergogenic aid in sport, but there is little evidence
      of its effectiveness during closed-loop athletic events. In order to determine
      the effectiveness of music as an ergogenic aid, well-trained and task-habituated
      cyclists performed 10-km cycle time trials either while listening to self
      selected motivational music or with auditory input blocked. There were no
      statistically significant differences in performance time or physiological or
      psychological markers related to music (time-trial duration17.75 +/- 2.10 vs
      17.81 +/- 2.06 min, mean power output 222 +/- 66 vs 220 +/- 65 W, peak heart
      rate184 +/- 9 vs 183 +/- 8 beats/min, peak blood lactate12.1 +/- 2.6 vs 11.9 +/-
      2.1 mmol/L, and final rating of perceived exertion 8.4 +/- 1.5 vs 8.5 +/- 1.6).
      It is concluded that during exercise at competitive intensity, there is no
      meaningful effect of music on either performance or physiology.

PMID- 22868290
TI  - Spontaneous healing of traumatic eardrum perforation: outward epithelial cell
      migration and clinical outcome.
AB  - OBJECTIVE: To characterize the otoendoscopic features of traumatic tympanic
      membrane perforations (TMPs) with outward-migrating epithelium at the perforation
      edges and to evaluate the spontaneous healing outcome of this type of
      perforation. STUDY DESIGN: Case series with chart review. SETTING: Tertiary
      university hospital. MATERIALS AND METHODS: The clinical records of traumatic TMP
      patients who met the case selection criteria were retrieved and categorized based
      on the documented migration pathways of the proliferating epithelial cells at the
      perforation margins into 2 groups: centripetal migration and outward migration.
      The demographic data and spontaneous healing outcomes (ie, healing rate and time)
      of these 2 types of TMP were analyzed using the chi-square test or t-test. The
      otoendoscopic features were characterized. RESULTS: In all, 122 cases were
      analyzed. During the spontaneous healing process, perforations were associated
      with centripetal epithelial cell migration in 87 (71.3%) cases and with outward
      epithelial cell migration in 35 (28.7%) cases. The overall perforation closure
      rates at the end of 6 months were 97% and 94% for the centripetal and outward
      migration groups, respectively (P > 0.05). The average perforation closure times
      were 18.4 +/- 3.7 and 37.6 +/- 9.2 days, respectively (P < 0.05). CONCLUSIONS:
      Although the outward epithelial migration did not affect the overall perforation
      spontaneous healing rate, it alone could not close the perforation. The
      prerequisite for eardrum healing is that the outward epithelium migration pattern
      evolves into a centripetal migration pattern. Consequently, outward epithelial
      migration prolonged substantially the time to traumatic eardrum perforation
      closure.

PMID- 22868291
TI  - Complete duplication of the bladder and urethra in the coronal plane: case report
      with review of the literature.
AB  - Complete duplication of the bladder and urethra without other congenital
      anomalies is a very rare congenital anomaly. We report the case of an 8-year-old
      boy with complete duplication of the bladder and urethra in the coronal plane,
      without any other associated congenital anomalies and without complaint
      associated with the urinary tract.

PMID- 22868292
TI  - Water sorption in ionic liquids: kinetics, mechanisms and hydrophilicity.
AB  - Most of the ionic liquids (ILs) are hygroscopic in air. The effects of structural
      factors of ILs (cation, anion, alkyl chain length at cation, and C2 methylation
      at cation) and external factors (temperature, relative humidity, and impurity) on
      the kinetics of water sorption by 18 ILs were investigated. A modified two-step
      sorption mechanism was proposed to correlate the water sorption data in the ILs.
      Three type of parameters (sorption capacity, sorption rate and degree of
      difficulty to reach sorption equilibrium) based on the modified two-step
      mechanism were derived to comprehensively characterize the water sorption
      processes. These parameters have similar tendencies, providing an efficient way
      to evaluate them by one parameter that can be easily obtained. The hydrophilicity
      of the ILs was classified to four levels (super-high, high, medium, low)
      according to the water sorption capacity. The results show that cation of the ILs
      also plays an important role in water sorption, and the impurities affect the
      water sorption enormously. Acetate and halogen-based ILs have the highest
      hydrophilicity when combined with the imidazolium or pyridinium cation.

PMID- 22868293
TI  - Deterioration of fracture healing in the mouse model of NF1 long bone dysplasia.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease resulting
      from inactivating mutations in the gene encoding the protein neurofibromin. NF1
      manifests as a heritable susceptibility to tumours of neural tissue mainly
      located in the skin (neurofibromas) and pigmented skin lesions. Besides these
      more common clinical manifestations, many NF1 patients (50%) have abnormalities
      of the skeleton. Long bones are often affected (usually the tibia) and the
      clinical signs range from bowing to spontaneous fractures and non-unions. Here we
      present the analysis of bone fracture healing in the Nf1(Prx1)-knock-out mouse, a
      model of NF1 long bone dysplasia. In line with previously reported cortical bone
      injury results, fracture healing was impaired in Nf1(Prx1) mice. We showed that
      the defective fracture healing in Nf1(Prx1) mice is characterized by diminished
      cartilaginous callus formation and a thickening of the periosteal bone. These
      changes are paralleled by fibrous tissue accumulation within the fracture site.
      We identify a population of fibrous tissue cells within the Nf1 deficient
      fracture as alpha-smooth muscle actin positive myofibroblasts. Additionally,
      histological and in-situ hybridization analysis reveal a direct contact of the
      fracture site with muscle fascia, suggesting a possible involvement of muscle
      derived cells in the fracture deterioration.

PMID- 22868294
TI  - Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort.
AB  - BACKGROUND: Glial tau pathology is seen in certain tauopathies and in ageing. We
      determined its frequency in ageing mesial temporal lobe and its relationship to
      other tau pathologies in the MRC-CFAS population-representative neuropathology
      cohort. METHODS: Mesial temporal lobe, including hippocampus, amygdala,
      entorhinal cortex and white matter, was examined using immunohistochemistry with
      the AT8 antibody to phospho-tau and RD3 and RD4 antibodies to 3R and 4R tau
      isoforms. Gallyas silver stain was used to detect fibrillar aggregates. RESULTS:
      Thorn-shaped astrocytes (TSA), positive with AT8, RD4 and Gallyas, were present
      in 49% of cases. They were particularly prevalent in subpial, periventricular and
      white matter perivascular locations and were less frequent in grey matter. Coiled
      bodies were seen in 18.8%. TSA were not related to Braak neurofibrillary tangle
      or hippocampal tangle pathology stages. TSA in grey matter were associated with
      coiled bodies (p = 0.011) and argyrophilic grains (p = 0.048), which were
      identified in 11.5% of cases. They did not correlate with dementia. CONCLUSIONS:
      Astrocyte tau pathology is common in the ageing mesial temporal lobe. Its
      formation is independent of Alzheimer-type pathology. It is a 4R tauopathy, which
      may form part of a mesial temporal age-related 4R tauopathy that includes
      oligodendroglial tau and argyrophilic grains.

PMID- 22868295
TI  - The efficacy of diagnostic imaging.

PMID- 22868296
TI  - Proximal caries detection accuracy using intraoral bitewing radiography,
      extraoral bitewing radiography and panoramic radiography.
AB  - OBJECTIVE: To compare proximal caries detection using intraoral bitewing,
      extraoral bitewing and panoramic radiography. METHODS: 80 extracted human
      premolar and molar teeth with and without proximal caries were used. Intraoral
      radiographs were taken with Kodak Insight film (Eastman Kodak Co., Rochester, NY)
      using the bitewing technique. Extraoral bitewing and panoramic images were
      obtained using a Planmeca Promax Digital Panoramic X-ray unit (Planmeca Inc.,
      Helsinki, Finland). Images were evaluated by three observers twice. In total, 160
      proximal surfaces were assessed. Intra- and interobserver kappa coefficients were
      calculated. Scores obtained from the three techniques were compared with the
      histological gold standard using receiver operating characteristic analysis. Az
      values for each image type, observer and reading were compared using z-tests,
      with a significance level of alpha = 0.05. RESULTS: Kappa coefficients ranged
      from 0.883 to 0.963 for the intraoral bitewing, from 0.715 to 0.893 for the
      extraoral bitewing, and from 0.659 to 0.884 for the panoramic radiography.
      Interobserver agreements for the first and second readings for the intraoral
      bitewing images were between 0.717 and 0.780, the extraoral bitewing readings
      were between 0.569 and 0.707, and the panoramic images were between 0.477 and
      0.740. The Az values for both readings of all three observers were highest for
      the intraoral bitewing. Az values for the extraoral bitewing images were higher
      than those of the panoramic images without statistical significance (p > 0.05).
      CONCLUSION: Intraoral bitewing radiography was superior to extraoral bitewing and
      panoramic radiography in diagnosing proximal caries of premolar and molar teeth
      ex vivo. Similar intra- and interobserver coefficients were calculated for
      extraoral bitewing and panoramic radiography.

PMID- 22868297
TI  - Three-dimensional visualization of composite fillings for dental identification
      using CT images.
AB  - OBJECTIVES: This study aimed to discriminate between enamel and composite resins
      by differences in Hounsfield units shown on 16 section multidetector CT (MDCT)
      images taken of unidentified bodies. METHODS: First, we determined the Hounsfield
      units of composite resins in 15 extracted human teeth. We then filled a single
      cavity prepared in each of the teeth with one of five different types of
      composite resins, and scanned the teeth using our routine post-mortem CT protocol
      for the head and neck. Obtained data were transferred to a radiological
      workstation and reconstructed. Furthermore, post-mortem CT images of the head of
      three unidentified bodies were reconstructed in the same manner. RESULTS: Four
      types of composite resins containing radio-opaque fillers showed a constant value
      of 4000 HU, and one radiolucent composite resin showed values in the range of 660
      800 HU in the extracted teeth. Pixels at 4000 HU indicated that the composite
      resins were selected and visualized as three-dimensional colour images. Composite
      resins could be visualized on reconstructed images of the three unidentified
      bodies, and the sites visualized matched those noted on the forensic dental
      charts. CONCLUSIONS: Discriminating enamel and composite resins containing radio
      opaque materials was difficult because of their similar Hounsfield unit values.
      However, we did succeed in visualizing the composite resins despite limitations
      of the CT scale. CT reconstructed images can contribute to dental identification,
      particularly in cases where it is difficult to detect composite resins on
      external investigation, and these images can be prepared during routine dental
      identification work.

PMID- 22868298
TI  - Harvey Cushing's surgical treatment of facial paralysis during his tenure at the
      Johns Hopkins Hospital.

PMID- 22868299
TI  - Immediate definitive prosthetic reconstruction in patients with ptotic breasts.
AB  - Immediate reconstruction of medium/large ptotic breasts can be performed by using
      expanders, definitive implants, or autologous flaps. If a skin-sparing mastectomy
      is feasible, excellent results can be achieved by planning Wise pattern
      incisions, using definitive implants. The authors suggest the use of a dermal
      adipose flap, harvested from the ptotic part of the breast, rotated laterally,
      and interposed between the serratus fascia and the pectoralis muscle to close the
      inferolateral part of the pocket. We performed 23 immediate unilateral single
      stage breast reconstructions, with simultaneous contralateral reduction.
      Preoperatively, all breasts showed grade II or III ptosis. There was no case of
      implant infection or failure of the reconstruction. The median follow-up was 21
      months; however, some patients followed up for >4 years; in this period, no case
      of capsular contracture was observed. This technique has provided good shape,
      acceptable ptosis consistent with the healthy breast and symmetric scars.

PMID- 22868301
TI  - The use of the multi-island vertical rectus abdominis myocutaneous flap in head
      and neck reconstruction.
AB  - BACKGROUND: Head and neck cancer extirpation frequently creates complex 3
      dimensional defects involving both intraoral and external tissues. Reconstruction
      can be accomplished either with 2 free flaps, a simultaneous free and pedicle
      flap, or a single double-island folded free flap. Herein, the outcomes and
      rationale for reconstruction of multilaminar head and neck defects using the
      multi-island vertical rectus abdominis myocutaneous (MI-VRAM) flap are reported.
      METHODS: A retrospective review was performed of a prospectively collected
      database of all head and neck reconstructions completed by a single surgeon
      between 1992 and 2011. Forty-six patients were identified who underwent
      reconstruction of composite defects using MI-VRAM flaps. Oncologic defects were
      classified into 3 categories based on anatomic location, namely, the midface,
      lower face, and neck. Indications and outcomes were reviewed. RESULTS: Patients'
      ages ranged from 7 to 84 years with two thirds being male; 45% received
      preoperative radiation. Average MI-VRAM skin paddle size was 9*25.5 cm. Of the 46
      reconstructions, 27 (59%) were performed in the midface, 14 (30%) in the lower
      face, and 5 (11%) in the neck region. There were no complete flap loses; however,
      1 patient lost the external skin island, requiring pectoralis flap coverage. Of
      these cases, 15% had surgically related complications. Ten patients required
      secondary contouring procedures to revise bulky flaps. CONCLUSIONS: The MI-VRAM
      flap is a safe and reliable technique for reconstruction of complex defects
      throughout the head and neck region. Compared to 2 simultaneous free flaps or a
      free flap combined with a regional flap, it saves time and eliminates a second
      donor site. LEVEL OF EVIDENCE: Level IV. Clinical question addressed in this
      paper is whether a multi-island VRAM flap is a safe technique in head and neck
      reconstruction.

PMID- 22868300
TI  - Perineal wound complications, risk factors, and outcome after abdominoperineal
      resections.
AB  - BACKGROUND: We describe the risk factors for complications and outcome of
      perineal wounds after abdominoperineal resections (APRs). METHODS: A
      retrospective chart review was performed, and patient demographics, risk factors,
      extent of APR, closure of perineal wounds, exposure to radiation, and outcome
      were collected. RESULTS: There were 87 APRs performed during an 8-year period.
      The mean follow-up period was 2.0 years (range, 18 days to 7.8 y). The mean body
      mass index (BMI) of the cohort was 27.8 kg/m (range, 16.8-47.5 kg/m). Of these
      patients, 36 (41%) have normal weight (BMI < 25 kg/m) and 51 (59%) were
      overweight (BMI > 25 kg/m). Direct closure of the perineum was performed in 67
      patients (77%). Twenty patients (23%) had musculocutaneous flap closures of the
      perineum. Fifty-seven patients (66%) had radiation exposure to the perineal
      region. Nineteen patients (22%) had complications of the perineal wound. We found
      that direct closure of the perineum in patients who were overweight (P < 0.05),
      active smokers (P < 0.05), or had chronic obstructive pulmonary disease (P <
      0.01) was associated with higher wound complications. CONCLUSIONS: The use of
      musculocutaneous flap closures of the perineum after APRs in patients who are
      overweight (BMI > 25 kg/m), are smokers, or have chronic obstructive pulmonary
      disease may decrease wound complications.

PMID- 22868302
TI  - Current trends in chaperone use by plastic and reconstructive surgeons.
AB  - PURPOSE: There is a paucity of literature regarding the use of chaperones by
      surgeons when examining patients. Use of a chaperone not only makes the patient
      comfortable but also potentially protects the surgeon from perceived misconduct.
      This is especially true for plastic surgeons who examine sensitive areas
      commonly. The purpose of this study was to determine the current trends in
      chaperone use by plastic surgeons when examining patients. MATERIALS AND METHODS:
      A 23-question online survey was sent to all members of the American Society of
      Plastic Surgeons. Data collected online were analyzed using Student t test and
      Pearson chi test. A P < 0.05 was considered significant. RESULTS: Of the 4990
      surgeons polled, 830 (16.6%) responded to some or all of the questions (707 [85%]
      male; 117 [14%] female). The overall chaperone use by plastic surgeons during all
      examinations of patients was 30%. This rate increased up to 60% while examining
      sensitive areas. Male surgeons reported a higher frequency of chaperone use than
      female surgeons (P < 0.001). Cosmetic surgeons had a higher rate of chaperone use
      compared to reconstructive surgeons (P = 0.001). Similarly, surgeons who had been
      in practice for more than 20 years reported a higher rate of chaperone use
      compared to surgeons in practice for less than 20 years (P = 0.032). Sixty-one
      (7.6%; 56 male and 5 female) surgeons reported being accused of inappropriate
      behavior by patients, of whom 49 (80%) did not have a chaperone present. There
      was no significant difference among male and female surgeons in rates of being
      accused of inappropriate behavior (7.9% vs 4.2%, P = 0.19). CONCLUSIONS: There
      was a higher rate of chaperone use by male plastic surgeons, surgeons with more
      than 20 years experience, and cosmetic surgeons. Despite the difference in
      chaperone use between the sexes, both had similar rates of being accused of
      inappropriate behavior during examinations by patients, and although these
      incidents were quite low, most had no chaperone present during those
      examinations.

PMID- 22868303
TI  - Reconstructive options in patients with late complications after surgery and
      radiotherapy for head and neck cancer: remember the deltopectoral flap.
AB  - During the past 40 years, free vascularized flaps have become the golden standard
      in the reconstruction of postoncologic head and neck defects. When there is a
      need for an osteofasciocutaneous free flap, the free fibula flap is the first
      choice because of the advantages of its long bone structure, high reliability,
      and minimal donor-site morbidity. However, most of these patients receive
      adjuvant radiation therapy, which sometimes causes symptomatic fibrosis,
      contractures, and (osteo)radionecrosis. In case of these late complications,
      locoregional reconstructive options are often limited, and complex secondary free
      flap procedures are not always feasible or preferred by the patient. The present
      paper discusses regional and free flap reconstructive options and demonstrates
      with 3 cases that the delayed deltopectoral flap remains a very safe, reliable,
      and easy flap, which still has a place in the management of these complex
      reconstructive challenges. 

PMID- 22868304
TI  - Perioperative hemodynamics in free flap breast reconstruction: incidence,
      predictors, and management of tachycardia.
AB  - BACKGROUND: The physiologic and hemodynamic changes occurring after abdominally
      based free flap breast reconstruction have not been well described. In this
      study, we examine perioperative circulatory and physiologic changes in an effort
      to identify risk factors and complications associated with postoperative
      tachycardia. METHODS: A retrospective review of all immediate abdominal free
      flaps performed by the senior author (J.M.S.) between 2005 and 2009 was
      performed. End points of interest included patient demographics, comorbidities,
      preoperative and postoperative heart rate (HR), mean arterial pressure, operating
      room fluid, pain score, urine output, and preoperative and postoperative
      hemoglobin. We define tachycardia as a sustained HR of 100 beats per minute or
      greater. Tachycardic patients were compared to patients with normal sinus rhythm.
      RESULTS: In 237 patients, 371 flaps were identified (103 unilateral and 268
      bilateral). There was a 36% overall incidence of tachycardia, with a 20% and 47%
      incidence in unilateral and bilateral flaps, respectively (P<0.0001).
      Preoperative HR, operating room fluid, estimated blood loss, and bilateral
      reconstruction predicted postoperative tachycardia. Regression analysis revealed
      that preoperative HR and internal mammary artery predicted tachycardia in
      unilateral flaps, whereas preoperative HR, operative time, and estimated blood
      loss predicted tachycardia in bilateral flaps. We found higher rates of wound
      healing complications and delayed venous thrombosis in tachycardic patients.
      CONCLUSIONS: Patient and perioperative factors associated with tachycardia
      include preoperative HR, bilateral reconstruction, recipient artery choice, and
      operative time. These results suggest that postoperative tachycardia may be
      associated with perfusion-related complications such as delayed wound healing and
      thrombosis. Preoperative assessment should include an evaluation of patient risk
      factors for postoperative tachycardia.

PMID- 22868305
TI  - A 2-year follow-up of irradiated homologous costal cartilage used as a septal
      extension graft for the correction of contracted nose in Asians.
AB  - BACKGROUND: Septal extension graft is a useful method for the correction of
      contracted nose. When septal or costal cartilage is not available, irradiated
      homologous costal cartilage (IHCC) may be an alternative choice. This preliminary
      study is focused on noninfective absorption and other complications and
      postoperative changes of nasal length after septal extension graft using IHCC.
      METHODS: Thirty patients who could be observed for more than 2 years
      postoperatively were assessed. All patients had contracted nose deformities with
      a history of an inflammatory contracture after previous aesthetic surgical
      procedures. The IHCC was used only as a septal extension graft in each patient.
      Nasal length was analyzed by comparing preoperative and 2-year postoperative
      photographs. RESULTS: There was no noticeable graft warping or infective IHCC
      absorption. However, 3 patients underwent revision: 2 cases of graft avulsion
      fracture and 1 case of minimal nasal obstruction. Nasal length, which had
      increased an average of 8.5% after the procedure, was maintained at follow-up 2
      years postoperatively. CONCLUSIONS: The IHCC has the advantages of avoiding donor
      site scars, and also provides the same benefits as autogenous costal cartilage.
      It can therefore be a reliable alternative material for rhinoplasty. A longer
      follow-up may be necessary to confirm the structural stability of the IHCC graft
      in the lengthened caudal septum.

PMID- 22868306
TI  - Examination of possible predictors of complications after free tissue transfer to
      the head and neck for oncologic defects.
AB  - INTRODUCTION: The advent of vascularized free tissue transfer marked an
      incredible addition to the breadth of options available to the reconstructive
      surgeon when treating head and neck defects. The goal of this study is to
      determine if readily available laboratory tests may be used to stratify the risk
      for developing complications after free tissue transfer in specific patients.
      METHODS: Institutional review board approval was obtained for a retrospective
      chart review of all patients who underwent free tissue transfer for
      reconstruction of oncologic head and neck defects between 2001 and 2010 by the
      senior author (R.O.D.). RESULTS: There were 107 free tissue transfers to the head
      and neck for oncologic defects during this period. A significant relationship was
      found between a preoperative hemoglobin less than 10 mg/dL and a postoperative
      albumin less than 2.5 mg/dL and complications. CONCLUSIONS: Preoperative
      hemoglobin less than 10 mg/dL and postoperative albumin less than 2.5 mg/dL seem
      to be useful as indicators of an increased likelihood of developing postoperative
      complications. Correction of these values preoperatively and postoperatively may
      lead to improved surgical outcomes.

PMID- 22868307
TI  - Comparison of native porcine skin and a dermal substitute using tensiometry and
      digital image speckle correlation.
AB  - Dermal substitutes are currently used in plastic surgery to cover various soft
      tissue defects caused by trauma, burns, or ablative cancer surgery. Little
      information is available on the biomechanical properties of these dermal
      substitutes after adequate incorporation as compared to normal skin. Determining
      parameters such as tensile strength in these skin substitutes will help us
      further understand their wound healing properties and potential in developing
      artificial tissue constructs. We hypothesize that a dermal substitute has a lower
      stress-strain curve and altered stress-induced deformation quantified with
      tensiometry and digital image speckle correlation (DISC) analysis. Two separate
      5*10-cm full-thickness wounds were created on the dorsum of 3 female swine.
      Fibrin glue was applied before either a full-thickness skin graft (FTSG) or
      application of artificial dermal matrix. On day 42, cultured autologous
      keratinocytes were applied as a cell sheet to the wound covered with Integra. On
      day 56, the wounds were fully excised and fresh tissue specimens, including
      normal skin, were stored in a physiological solution and prepared for analysis.
      Rectangular samples were excised from the center of each specimen measuring
      4*4*30 mm. Using a tensiometer and DISC analysis, we evaluated the tensile
      strength of 3 different groups of skin, namely, normal, FTSG, and Integra. There
      is a significant difference between the Integra specimen when compared to normal
      skin and FTSG. We found a minimal difference in the stress-strain curves of the
      latter two. Integra alone shows plastic deformation with continued stretching
      before ultimate midline fracture. There is significant change between the Young's
      moduli of the normal skin and the Integra, whereas there is little difference
      between the FTSG and the normal skin; DISC confirms this analysis. The normal
      skin and FTSG show a convergence of vectors to a linear plane, whereas Integra
      shows very little organization. Using 2 different methods of analysis, we have
      shown a dermal substitute does not display similar biomechanical properties after
      adequate incorporation. These major tensile strength differences are shown
      between normal, grafted, and Integra constructs under physiological conditions.
      These properties will lead to further understanding of artificial tissue and
      engineered constructs in laboratory and clinical applications.

PMID- 22868308
TI  - The fleur-de-lis upper gracilis flap for breast reconstruction: flap design and
      outcome.
AB  - We evaluated a fleur-de-lis design for the gracilis myocutaneous flap to improve
      flap volume for breast reconstruction. Thirty-one flaps were used in 17
      consecutive patients undergoing the procedure for either thin body habitus (23
      flaps) or prior abdominal surgery (8 flaps). The flap success rate was 100%. The
      fleur-de-lis flap provided proportionate breast reconstructions in all patients.
      Complications included 6 (19.3%) donor-site dehiscence and 4 (12.9%) episodes of
      cellulitis. Applying a negative pressure dressing to the donor site (n=26)
      significantly reduced the initially high dehiscence rate to 7.7% (P<0.01). There
      was no incidence of lower extremity edema or sensory loss. The fleur-de-lis
      gracilis flap can be performed with a low flap related complication rate and
      acceptable donor-site morbidity. Because of its standardized flap design,
      improved volume, and favorable breast shaping, it may allow autologous breast
      reconstruction to be offered to a greater number of patients.

PMID- 22868309
TI  - A 10-year review of breast reconstruction in a university-based public hospital.
AB  - BACKGROUND: Breast reconstruction rates continue to slowly rise in large part
      because of patients and physicians becoming more knowledgeable about
      postmastectomy options. Overall satisfaction with breast reconstruction after
      mastectomy has traditionally been high, only adding to the popularity of this
      choice. Prior research has demonstrated that race, age, and socioeconomic status
      are important determinants in whether a patient undergoes breast reconstruction;
      specifically, indigent women have a lower rate of breast reconstruction when
      compared to the national average. METHODS: All records of patients who received
      mastectomies between January 2001 and December 2009 were examined. The PubMed
      database was used to search for reference articles. RESULTS: Between January 2001
      and December 2009, 309 patients underwent mastectomy, and 134 (43.4%) elected
      reconstruction. Patients in age ranges 20 to 39 and 40 to 59 were both
      significantly more likely to undergo reconstruction than patients older than 60
      years. Disease stage was not significantly related to rates of breast
      reconstruction. Reconstruction rates by race and ethnicity were analyzed and
      demonstrated a significantly lower rate of breast reconstruction in Asian women
      (34%) compared with Hispanic women (48%), despite the same access to available
      services. CONCLUSIONS: Our data demonstrate breast reconstruction rates
      significantly higher than prior studies for women in this public hospital
      demographic, rivaling the reported numbers from dedicated cancer centers where
      breast reconstruction is expected to be at the highest range. Types of
      reconstruction were based mainly on patient choice after full discussion
      regarding individual options. These data suggest that patients considered to be
      financially indigent are more likely to have breast reconstruction when their
      care is delivered at a university-based public hospital where immediate and
      consistent patient education is practiced in a multidisciplinary setting.

PMID- 22868310
TI  - Delayed diagnosis of hand injuries in polytrauma patients.
AB  - Trauma patients are at high risk for delayed diagnosis of injuries, including
      those to the hand, with reports in the literature as high as 50%. As a result,
      patients may have prolonged disability and longer hospital stays with associated
      increased costs. Our objective was to elucidate risk factors for the delayed
      diagnosis of hand injuries. A review was performed from 2000 through 2009,
      assessing for age, sex, blood alcohol level, Glasgow Coma Score (GCS), Injury
      Severity Score (ISS), mechanism, injury type, length of stay, and timing of hand
      injury diagnosis. In this study, 36,568 patients were identified; 738 meeting
      criteria; 21.7% of patients had delayed diagnoses with 91.3% of patients
      diagnosed by the day after admission. Delayed diagnoses were more than 2 times
      higher for severely injured patients. Patients with delayed diagnoses had a lower
      GCS and a higher ISS and length of hospitalization. With a decreased GCS and
      elevated ISS, patients are at risk for delayed diagnoses of hand injuries. A
      focused tertiary survey is mandatory, particularly in patients with an altered
      mental status or with multiple injuries.

PMID- 22868311
TI  - Reduction mammaplasty trends: a quality and fiscal analysis update.
AB  - BACKGROUND: Reduction mammaplasty remains one of the most common procedures
      performed by plastic surgeons today. The national health care quality and fiscal
      environments continue to evolve, with increasing emphasis on outpatient
      procedures and reduced lengths of stay (LOS). This study was designed to analyze
      the trends in reduction mammaplasty at our institution during the last 10 years
      with particular attention to LOS, complication rate, and readmission. We also
      evaluated the institutional fiscal implications with regard to reimbursement in
      the changing health care environment. MATERIALS AND METHODS: Institutional review
      board approval was obtained for this retrospective chart review. An analysis of
      all reduction mammaplasties during the last 10 years was undertaken. Admission
      status [same day surgery (SDS), outpatient ambulatory, observation, and
      inpatient], LOS, mortality, morbidity, and readmissions were documented. A
      financial analysis was also performed comparing trends in hospital revenue and
      operating income. Revenue was defined as the amount that the hospital received
      from all sources, whereas operating income was the revenue reduced by all costs
      incurred to provide services. RESULTS: In this population, 1779 patients were
      identified (SDS, 499; outpatient ambulatory or observational, 694; and inpatient,
      586). Twenty patients were readmitted within 30 days. The all-cause 30-day
      readmission rate was 11.24 per 1000 patients. The disease-specific readmission
      rate was 5.06 per 1000 patients (n=9). Only 1 patient with disease-specific
      complication requiring readmission had been classified as SDS. No cases of nipple
      compromise were identified in our study. Revenue per case was highly variable
      throughout the study period. In general, operating income has decreased during
      the last decade, despite a small increase for those patients who were truly
      inpatient. CONCLUSIONS: Reduction mammaplasty is a common procedure that is safe
      when performed on an outpatient basis. Institutional operating income, except in
      the case of inpatients, continues to decrease and could pose a challenge in the
      future should present trends continue.

PMID- 22868312
TI  - Level I sparing radical neck dissections for cutaneous melanoma in the
      lymphoscintigram era.
AB  - INTRODUCTION: Excision of regional lymph nodes (LNs) in the neck as part of the
      management for tumors of the head and neck dates back to the 19th century. Crile
      originally reported the technique of performing a radical neck block dissection
      in 1905, with notable modifications to the extensive dissection reported
      throughout the 20th century by Suarez, Ballantyne, Ariyan, and Shah among others.
      These modifications have aimed to reduce the morbidity encountered by performing
      the radical neck dissection while balancing the need to remove diseased
      structures in the head and neck. In this report, we evaluate the outcomes of
      performing a functional radical neck dissection while sparing the level I LNs as
      indicated by lymphoscintigraphy. METHODS: The charts of patients from the Yale
      Melanoma Unit who underwent resection of their head and neck melanoma from
      January 2000 to December 2006 were reviewed. The location of the primary melanoma
      and clinical course was noted. Those patients who underwent neck dissections were
      documented and the extent of the dissections from the operative reports was
      noted. Demographic and outcome data were recorded, including clinical course of
      melanoma presentation, local recurrence, and postoperative management. Student t
      test and chi tests were used to determine statistical significance between
      groups. P values less than 0.05 were considered statistically significant.
      RESULTS: A total of 41 patients who were documented to have had a head and neck
      primary melanoma underwent a functional radical neck dissection. Level I
      dissections were deemed necessary in 39% of these cases, whereas 61% of patients
      received functional radical neck dissections with sparing of level I LNs.
      Specific recurrence of melanoma in the submandibular basin was equivocal for LN
      sparing dissections (n=1) as compared to excision of level I LNs (n=1) (4% vs
      6.25%, P=0.488). Follow-up metastatic rates between the 2 groups were also
      comparable (44% vs 56%, P=0.328). Overall metastatic rate in follow-up for all
      patients undergoing LN dissection was 48.8%. There was no statistically
      significant difference between the average age of patients at diagnosis, Breslow
      depth, Clark level, and staging between patients who underwent functional radical
      neck dissections with either excision or sparing of level I LNs. CONCLUSIONS:
      Clinical and pathological presentation between patients who needed level I
      sparing dissections and those who did not, failed to demonstrate a statistically
      significant difference allowing for an adequate comparison. Our results indicate
      that if lymphoscintigraphy does not show drainage to level I LNs, the functional
      radical neck dissection can be tailored to spare level I LNs without affecting
      local recurrence. When not indicated by lymphoscintigram, sparing of level I
      nodes can be performed safely without changing clinical outcomes, while saving
      operating room time and minimizing potential damage to the buccal branch of
      facial nerve and the submandiblular gland.

PMID- 22868313
TI  - Complications in tissue expander breast reconstruction: a comparison of AlloDerm,
      DermaMatrix, and FlexHD acellular inferior pole dermal slings.
AB  - Acellular dermal matrix (ADM) is frequently used in tissue expander breast
      reconstruction (TEBR) for coverage of the inferior pole. Several published
      studies have suggested increased rates of complications with the use of ADM. It
      is unknown, however, if the type of ADM used for TEBR impacts complication rates.
      The aim of this study is to compare 3 different types of ADM for TEBR in regard
      to clinically significant complications, specifically infection. We performed a
      retrospective analysis of primary breast cancer-related TEBR with or without ADM.
      Exclusion criteria consisted of prior major breast surgery, inadequate data, or
      loss to follow-up. Reconstructions were grouped by dermal sling type, AlloDerm,
      DermaMatrix (DM), FlexHD (FHD), or no ADM. Complications included cellulitis,
      abscess, seroma, expander leak or puncture, skin necrosis, wound dehiscence, or
      hematoma. Those requiring admission to hospital or reoperation were considered
      significant. Of 284 breasts reconstructed, 49 used AlloDerm, 110 used DM, 62 used
      FHD, and 64 used no ADM. The total complication rate with AlloDerm was 22% [95%
      confidence interval (CI), 11-34], with DM was 15% (95% CI, 8-21), and with FHD
      was 18% (95% CI, 8-28) (P=0.47). Infectious complication rates for AlloDerm, DM,
      and FHD were equal at 10% (P=0.97). The total complication rate of all ADM
      reconstructions as a grouped cohort was 17% compared to 11% without ADM (P=0.48).
      The overall incidence of infectious complications with ADM was 10% compared to 2%
      without ADM (P=0.09). There is no difference in the clinically significant
      overall complication rate or incidence of infection between AlloDerm, DM, and
      FHD. Isolating infectious complications, there is a trend toward increased
      incidence with ADM compared to reconstructions without.

PMID- 22868314
TI  - Better to light a candle: Arthur Barsky and global plastic surgery.
AB  - Plastic and reconstructive surgery has had a long history with international
      humanitarian efforts. As the field of global surgery continues to gain momentum
      in academic centers throughout the world, the role of the surgical subspecialist
      in the public health infrastructure of low-resource communities has also begun to
      gain a new sense of wonder and importance. Arthur Barsky, Jr was arguably one of
      the most influential forefathers of global plastic surgery. Throughout his
      notable career spanning most of the 20th century, Barsky remained dedicated to
      delivering plastic and reconstructive surgical care to the disadvantaged
      worldwide, as well as educating others to do the same. Although he was not the
      first surgeon with an interest in global health, Barsky's work was unique and
      influential in its originality, magnitude, and scope. An appreciation and
      understanding of Barsky's groundbreaking work will help inform the future
      development of sustainable surgical systems in resource-poor settings. 

PMID- 22868315
TI  - Restoration of the medial epicanthal fold: reverse skin redraping method in
      patients unsatisfied with epicanthoplasty.
AB  - BACKGROUND: Many Asians receive epicanthoplasty to improve their medial
      epicanthal fold.Excessive performance of such surgery may cause multiple unwanted
      results, but there is no report on any restoration method for an overcorrected
      result of epicanthoplasty. Accordingly, the authors have created a new method for
      reversely restoring the excessively corrected medial epicanthal fold using skin
      redraping epicanthoplasty (Plast Reconstr Surg. 2007;119:703-710). METHODS:
      During the interval between January 2009 and April 2011, 35 patients received
      surgery for restoration of the epicanthal fold using the authors' method, which
      involves sufficiently elevating the skin flap and redraping it to reconstruct the
      epicanthal fold. This method is very simple to design and perform, and it
      effectively covers the excessively exposed lacrimal lake. In addition, it can be
      used independently of the type of prior epicanthoplasty. RESULTS: After the
      surgery, 2 patients experienced overcorrection, and we repeated the
      epicanthoplasty. In the other patients, there was no severe complication except
      for mild redness, a condition that improved after several months. The mean
      measured distance between the medial canthi after the surgery was 36.8 mm,
      corresponding to a total lengthening effect of 4.5 mm. This improved the
      aggressive facial expression caused by the exposed lacrimal lake, and the eyes no
      longer appeared to be too close together. Moreover, in the case of patients who
      had more visible scars due to prior epicanthoplasty on the medial epicanthal
      area, the overall scar length decreased. CONCLUSIONS: This method is simple in
      design and easy to perform. It can also control the degree of restoration with an
      additional advantage of reducing a prior scar. Using this method, we could
      effectively restore the overcorrected epicanthal fold.

PMID- 22868316
TI  - Bevacizumab and wound-healing complications: mechanisms of action, clinical
      evidence, and management recommendations for the plastic surgeon.
AB  - Reflecting the growing understanding of vascular endothelial growth factor (VEGF)
      in cancer survival and growth, the anti-VEGF antibody bevacizumab (Avastin) is
      increasingly used to treat advanced malignancy. However, because VEGF also
      mediates proper wound healing, bevacizumab may lead to potentially severe wound
      healing complications (WHCs). Because bevacizumab expands in use, the plastic
      surgeon will increasingly be entrusted to manage such WHCs successfully.
      Therefore, this review summarizes the pathophysiological evidence, systematically
      reviews the available clinical evidence, and provides management guidelines for
      bevacizumab-related WHCs. Bevacizumab produces WHCs by disrupting vasodilation,
      increased vascular permeability, and angiogenesis. Current clinical evidence
      suggests that bevacizumab may increase WHC risk. This risk seems higher with
      neoadjuvant than adjuvant bevacizumab use and may be decreased by extending the
      bevacizumab-surgery interval. Further research is required to quantify the exact
      bevacizumab-related WHC incidence and optimize the bevacizumab-surgery interval.
      We propose management guidelines for bevacizumab-related WHCs by indication that
      should be integrated with clinical judgment, input from the oncology team, and
      patient wishes when making therapeutic decisions. 

PMID- 22868317
TI  - Use of anteromedial thigh flaps as an alternative to anterolateral thigh flaps
      for reconstruction of head and neck defects in cancer patients.
AB  - BACKGROUND: To determine whether anteromedial thigh (AMT) flaps are a good choice
      for reconstruction in cases in which no sizable skin perforator is found in
      anterolateral thigh (ALT) flap dissection or ALT flaps have been previously
      harvested. METHODS: From February 2006 to August 2008, 17 free AMT flaps were
      used to reconstruct soft tissue defects of the head and neck. We recorded the age
      and sex of the patients, sites of primary tumor, tumor stage, size of defect,
      previous operative conditions, results of flap transfer, and donor-site
      complications. RESULTS: Of the 17 AMT flaps, 1 flap failed and 1 showed partial
      necrosis. Venous insufficiency developed in 2 cases, and the flaps were
      successfully salvaged in both the cases. The success rate was 94.1%. The AMT
      flaps were 6 to 20 cm long and 4 to 9 cm wide. The mean length of the pedicle was
      7.5 +/- 1.0 cm (range, 5-12 cm). Of the 17 donor sites, 6 were closed directly, 9
      were closed using split-thickness skin grafts, and 2 were closed using full
      thickness skin grafts. Complications and morbidity of the donor site were
      minimal. CONCLUSIONS: Cases in which no sizable perforator is found or an ALT
      flap has been previously harvested pose an aesthetic challenge, and an AMT flap
      is a good alternative for performing successful reconstruction in such cases.

PMID- 22868318
TI  - Inclusion and exclusion criteria to overcome bias and reach a valid conclusion
      for interpositional flap coverage in primary hypospadias repair with tubularized
      incised plate urethroplasty.
AB  - BACKGROUND: There is no general consensus about the best vascularized layer
      between the neourethra and the skin in tubularized incised plate urethroplasty
      (TIPU) of Snodgrass. Inclusion of 1 surgeon to repair specific forms of
      hypospadias by using determined surgical materials and exclusion of definite
      patients and conditions and definite anomaly parameters may present the needed
      reliable data about the role of a specific type of interpositional coverage of
      the neourethra. PATIENTS AND METHODS: The 37 patients had been operated by TIPU
      with a ventral subcutaneous dartos flap covering the neourethra who designed as
      group A, while 26 patients had been operated by the standard TIPU without
      urethral coverage who designed as group B. RESULTS: Good cosmetic results were
      obtained in 93.65% of the patients. In group A, urethral fistulae were
      encountered in 2 cases of distal hypospadias and 1 case of midpenile hypospadias
      with a total fistula rate of 8.1%. In group B, urethral fistulae were found in 5
      cases of distal hypospadias and 3 cases of midpenile hypospadias with a total
      fistula rate of 30.7%. CONCLUSIONS: Flapless repair should not be tried as long
      as there is the needed experience to harvest a well-vascularized coverage.
      Interpositional flap coverage of the neourethra is crucial to decrease the rate
      of fistula in primary hypospadias TIPU repair. However, before designating a
      relative study, different forms of the anomaly, surgeon's experience, the
      potential harvesting complications, complexity degrees of different repairs, and
      the used surgical materials should be really considered.

PMID- 22868319
TI  - Outcomes of the surgical treatment of peripheral neuromas of the hand and
      forearm: a 25-year comparative outcome study.
AB  - PURPOSE: Peripheral neuromas within the upper extremity result in significant
      disability. Treatment options vary, and established protocols have yet to be
      determined. We performed a long-term outcome comparison examining different
      treatment options for peripheral upper extremity neuromas to determine which
      method provided superior results using a validated upper extremity outcome
      measurement system. METHODS: A retrospective chart review was performed for all
      patients undergoing surgical intervention from 1980 to 2005 for a symptomatic
      neuroma of the hand or forearm. Patients' charts were reviewed for medical
      history, etiology of neuroma, and treatment outcomes. Patients were surveyed
      using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and
      pain evaluation questionnaires. RESULTS: We identified 127 eligible patients who
      had their index procedure performed at our institution. Fifty-six patients
      completed the questionnaires. In all cases, verification of a neuroma was made on
      pathologic and surgical examination. Follow-up averaged 240 months from the time
      of surgery. Mean age at the time of surgery was 40 years (range, 19-72 years). Of
      all the patients, 11 were treated with muscle or bone transposition, 17 with
      simple excision, and 28 with nerve repair and neurolysis. Mean DASH score at the
      final follow-up was 19.75 (range, 0-78.3). Patients who underwent neuroma
      excision with nerve repair had significantly lower postoperative DASH scores,
      averaging 11.42, compared with either muscle or bone transposition or simple
      excision (mean DASH score, 22.4 and 32.0, respectively, P = 0.01). The number of
      neuroma procedures (P = 0.04), preoperative pain severity (P = 0.03), and
      postoperative pain severity (P = 0.04) all affected the final DASH score. Fifteen
      patients (27%) required more than 1 surgery. Simple neuroma excision resulting in
      the highest incidence of reoperations (47%). CONCLUSIONS: Treatment of upper
      extremity neuromas remains a complicated problem. Within this study, nerve repair
      yielded improved DASH scores compared with nerve transposition or the use of
      simple resection. Resection alone was associated with an unacceptable recurrence
      rate and should be discouraged as treatment for upper extremity neuromas. Prior
      surgical procedures, neuroma size, and the severity of preoperative pain may all
      adversely impact the success of surgical intervention.

PMID- 22868320
TI  - Graphic aids for calculation of fluid resuscitation requirements in pediatric
      burns.
AB  - The Parkland formula is currently the most widely used protocol to guide fluid
      resuscitation of acute burns and has been adapted for pediatric use. We describe
      3 novel graphic devices (a nomogram, slide rule, and disc calculator) based on
      this formula, which have significant advantages over existing graphic and
      electronic devices. The robust low-cost graphic devices would be particularly
      suited to developing countries and difficult locations, but could be used as the
      primary means of calculation in any environment. If a computer or calculator is
      used as the primary means of calculation, the graphic devices provide a simple
      and rapid means of checking and preventing errors that may arise because of
      inadvertent mis-keying of data or incorrect application of the pediatric Parkland
      formula.

PMID- 22868321
TI  - Versatility of the superficial circumflex iliac artery perforator flap in head
      and neck reconstruction.
AB  - The superficial circumflex iliac artery perforator (SCIP) flap was first reported
      in 2004, in which the concept of perforator flap was incorporated into the groin
      flap. Although a SCIP flap has many advantages, reports on its application to
      head and neck defects are limited. We present cases of SCIP flap transfer for
      reconstruction of various types of head and neck defects.Twelve patients
      underwent reconstruction using the free SCIP flap after tumor ablative surgery in
      the head and neck region. The flap was elevated based on the perforators of the
      superficial branch and/or deep branch of the superficial circumflex iliac artery.
      The thickness of the flap was adjusted according to the defect. The Photo Dynamic
      Eye infrared camera system using indocyanine green was used to detect the
      location of the perforators preoperatively and to confirm the blood flow after
      elevation of the flap. The flaps survived completely in all the cases. The mean
      pedicle length was 7.1 cm (range, 6-9 cm), and the mean flap size was 12.8 * 6.3
      cm (range, 4 * 2 to 18 * 8 cm). No vein grafting was necessary in any patient.The
      advantages of the SCIP flap include 1) low donor-site morbidity; the donor site
      is in a hairless concealed area, primary donor-site closure is possible, and no
      muscular dissection is necessary; 2) adjustable thickness of the flap from a
      superthin flap to a bulky flap; and 3) a long vascular pedicle available.We
      believe that the SCIP flap will become one of the most versatile options in head
      and neck reconstruction. 

PMID- 22868322
TI  - An evidence-based approach to the surgical management of pressure ulcers.
AB  - OBJECTIVE: This study aims to use the evidenced-based approach to better
      understand the surgical management and treatment of pressure ulcers. SUMMARY OF
      BACKGROUND DATA: Pressure sores are a cause of significant morbidity in the
      medical community. Although there are a multitude of preventative and treatment
      options, there remains some degree of uncertainty in the literature in defining
      the best way to treat and manage pressure sores. METHODS: An exhaustive
      literature search was performed using several electronic databases. The search
      revealed several identified modalities for treatment of pressure ulcers. We then
      assessed each modality individually for the level of evidence that exists in the
      most current literature, with preference given to more recent studies (2005
      present). RESULTS: Here, we reviewed the most relevant, high-level evidence that
      exists for the following modalities for managing pressure ulcers from a surgical
      perspective: wound cleansers, repositioning, negative pressure therapy, enteral
      and parenteral feeding, vitamin and mineral supplementation, specialized
      mattresses, ultrasound therapy, honey, cellular therapy, debridement, ostectomy,
      and musculocutaneous and fasciocutaneous flap closure. CONCLUSIONS: Although many
      of the previously mentioned modalities are used, we encourage clinicians and
      health care providers to consider the evidence-based data when deciding how to
      most appropriately manage their patient's pressure sores.

PMID- 22868323
TI  - Further evidence for treatment of recalcitrant neuropathy of the upper limb with
      autologous vein wrapping.
AB  - The treatment of entrapment neuropathy in the upper extremity with surgical
      decompression has generally provided good results. Recurrence of symptoms,
      however, is not uncommon, and its management is both challenging and difficult.
      Autologous vein graft wrapping is an alternative technique, and it is recommended
      for the treatment of recalcitrant upper limb nerve compression in which 2 or more
      previous surgical procedures have failed to resolve the problem. Each patient
      underwent both subjective and objective evaluation. To our knowledge, this is the
      largest reported single series of vein wrapping cases in the upper limb outside
      the United States and the first to report results using the well-validated
      patient evaluation measure.

PMID- 22868325
TI  - The quality of aesthetic surgery training in plastic surgery residency: a survey
      among residents in Germany.
AB  - BACKGROUND: The importance of providing high-quality exposure and training in
      aesthetic and reconstructive surgery during residency has come to the forefront
      of plastic surgery education. Adequate training in aesthetic surgery, however,
      has traditionally been challenging. The authors were interested in how these
      challenges were met abroad. METHODS: A 17-item online survey was developed to
      assess the quality of training in aesthetic surgery in Germany. The survey had 3
      distinct sections: demographic information, current state of aesthetic surgery
      training, and residents' opinions about the perceived quality of aesthetic
      surgery training. Only responses of senior residents were included in the final
      analysis. RESULTS: A total of 112 residents responded (30% response rate), of
      which 88 were senior plastic surgery residents. Ninety percent (n = 79) reported
      that a resident aesthetic surgery clinic was not part of their training
      experience. Eighty-eight percent (n = 77) reported that they did not have a
      dedicated aesthetic surgery rotation during their residency training. According
      to 69.3% (n = 61), no didactic training in aesthetic surgery was provided. Fifty
      six percent (n = 49) of senior plastic surgery residents had performed only a
      maximum of 10 aesthetic surgery procedures at the time of the survey. Although
      only 43.2% of senior residents claimed to be interested in a predominantly
      aesthetic surgery practice, 90.9% (n = 80) felt that they require further
      training in aesthetic surgery (ie, fellowship). CONCLUSIONS: Deficiencies exist
      with respect to aesthetic surgery training among senior plastic surgery residents
      in Germany. Structural improvements in residency training with formal exposure
      and teaching in aesthetic surgery are warranted. The German Society of Plastic,
      Reconstructive and Aesthetic Surgeons is actively addressing deficiencies
      identified with the goal of improving the quality of training.

PMID- 22868324
TI  - Management of thoracic aortic graft infections with the omental flap.
AB  - BACKGROUND: Infection of thoracic aortic grafts occurs infrequently; however,
      once present, it is associated with high patient morbidity and mortality. We
      report our successful experience in the treatment of 11 patients who developed
      infection of their thoracic aortic graft. METHODS: This is an institutional
      review board-approved retrospective review of 11 patients who had documented
      thoracic aortic graft infections with associated mediastinitis or empyema. After
      diagnosis, plastic surgery consultation was obtained, and the patients underwent
      formal operative debridement with cardiovascular service. Intraoperative cultures
      were obtained, and the patients were placed on specific antibiotic regimens.
      After the wound bed was adequately prepared, the omentum was harvested and was
      based on the right gastroepiploic vessels. The flap was circumferentially wrapped
      around the aortic graft and simultaneously used to fill the mediastinal dead
      space. In a certain subset of patients, a cryopreserved homograft replaced the
      synthetic graft before omental flap reconstruction. RESULTS: The infections were
      eventually controlled in all surviving patients. Ten of 11 patients were
      discharged either to a rehab or to a nursing facility. There was 1 perioperative
      death secondary to multisystem organ failure. Mean follow-up period was 36 months
      and revealed a greater than 90% survival rate. Serial imaging reported no suture
      line complications. CONCLUSIONS: We report our series on the treatment of
      patients with infection of thoracic aortic grafts. Debridement and tissue
      coverage with an omental flap provided these patients with successful recovery
      and survival.

PMID- 22868326
TI  - The impact of nipple reconstruction on patient satisfaction in breast
      reconstruction.
AB  - BACKGROUND: Nipple reconstruction is an integral part of the breast
      reconstruction process, as patients associate this stage with closure while
      providing a sense of completeness. This study evaluates the effect of nipple
      reconstruction on patient satisfaction with breast reconstruction. METHODS: All
      patients at Beth Israel Deaconess Medical Center undergoing breast reconstruction
      between 1999 and 2006 were identified. Patient demographics and complications
      were collected retrospectively while aesthetic and general satisfaction was
      evaluated by an administered survey. Patients with nipple reconstruction at the
      time of survey were compared to patients without nipple reconstruction. RESULTS:
      Nine hundred two breast reconstructions were performed in 696 patients; 490
      patients underwent nipple reconstruction and 206 did not. Autologous
      reconstruction predominated in patients with and without nipple reconstruction
      (61.8% and 54.8%, respectively). There were no significant differences in
      individual and overall total complications between groups. Patients with nipple
      reconstruction had significantly higher general (72.2% vs 52.8%, P<0.0001) and
      aesthetic (70.5% vs 46.5%, P<0.0001) satisfaction scores compared to patients
      without nipple reconstruction. These results were seen in unilateral and
      bilateral breast reconstruction. Across reconstructive techniques, patients with
      nipple reconstruction had higher aesthetic satisfaction. Patient satisfaction
      scores in all individual survey questions were statistically higher in patients
      with nipple reconstruction. CONCLUSIONS: Patients with breast reconstruction who
      undergo nipple reconstruction have higher general and aesthetic satisfaction
      compared to breast reconstruction alone. These differences were observed in both
      unilateral and bilateral reconstruction. Patients should be fully counseled about
      potential benefits nipple reconstruction can provide to all forms of breast
      reconstruction.

PMID- 22868327
TI  - Incisional negative-pressure wound therapy versus conventional dressings
      following abdominal wall reconstruction: a comparative study.
AB  - BACKGROUND: Improvements in surgical techniques have allowed us to achieve
      primary closure in a high percentage of large abdominal hernia repairs. However,
      postoperative wound complications remain common. The benefits of negative
      pressure wound therapy (NPWT) in the management of open abdominal wounds are well
      described in the literature. Our study investigates the effects of incisional
      NPWT after primary closure of the abdominal wall. METHODS: A retrospective chart
      review was performed for the period between September 2008 and May 2011 to
      analyze the outcomes of patients treated postoperatively with incisional NPWT
      versus conventional dry gauze dressings. Patient information collected included
      history of abdominal surgeries, smoking status, and body mass index.
      Postoperative complications were analyzed using chi exact test and logistic
      regression analysis. RESULTS: Fifty-six patients were included in this study; of
      them, 23 were treated with incisional NPWT, whereas 33 received conventional
      dressings. The rates of overall wound complications in groups I and II were 22%
      and 63.6%, respectively (P = 0.020). The rates of skin dehiscence were 9% and
      39%, respectively (P = 0.014). Both outcomes achieved statistical significance.
      Rates of infection, skin and fat necrosis, seroma, and hernia recurrence were 4%,
      9%, 0%, and 4% for group I and 6%, 18%, 12%, 9% for group II, respectively.
      CONCLUSIONS: This study suggests that incisional NPWT following abdominal wall
      reconstruction significantly improves rates of wound complication and skin
      dehiscence when compared with conventional dressings. Prospective, randomized,
      controlled studies are needed to further characterize the potential benefits of
      this therapy on wound healing after abdominal wall reconstruction.

PMID- 22868328
TI  - Computed tomographic angiography imaging and clinical implications of internal
      mammary artery perforator vessels as recipient vessels in autologous breast
      reconstruction.
AB  - The internal mammary artery (IMA) is the standard recipient vessel for autologous
      breast reconstruction. To save the IMA for bypass surgery, to keep flap pedicles
      short, and to allow better flap positioning, the IMA perforators were used. Forty
      six flaps for immediate breast reconstructions were performed in 39 patients. In
      the first 22 patients, the decision to use the perforators was clinically based.
      In the second group of 17 patients, all patients received a thoracic computed
      tomographic angiography (CTA) to determine the perforators. In 13 flaps (6 deep
      inferior epigastric artery perforator, 3 superficial inferior epigastric artery,
      and 4 transverse myocutaneous gracilis), the perforators were used as recipient
      vessels. Of these flaps, 5 were anastomosed to perforators before the CTA was
      applied and 8 after the CTA was established. The CTA revealed the IMA and the
      perforators in detail. In immediate reconstructions, the IMA perforators can be
      used as recipient vessels. They allow better flap positioning for superficial
      inferior epigastric artery and transverse myocutaneous gracilis flaps in
      particular; moreover, it decreases donor site and recipient site morbidity. After
      introducing the CTA, the perforators were used more frequently for anastomosis. 

PMID- 22868329
TI  - Early postoperative outcomes associated with the anterolateral thigh flap in
      Gustilo IIIB fractures of the lower extremity.
AB  - PURPOSE: A core concept in plastic surgery has been the replacement of "like-with
      like" tissue. Applying this concept to the lower extremity, the anterolateral
      thigh (ALT) perforator flap has become a frequently used free flap for
      restoration of soft tissue defects involving the distal lower extremity. The
      objective of this study was to evaluate the rate of early postoperative
      complications associated with the ALT perforator free flap for coverage of high
      energy traumatic open fractures of the lower extremity (Gustilo IIIB) and explore
      related patient risk factors. METHODS: A retrospective chart review of 74
      patients undergoing free tissue transfer for lower extremity limb coverage was
      performed. Early postoperative complications were defined as any 1 or more of the
      following having occurred within 6 months from surgical reconstruction: hematoma,
      wound infection, deep venous thrombosis, thromboembolism, partial flap loss,
      complete flap loss, continued osteomyelitis, and progression to amputation
      occurring within the first 6 months after the injury. Statistical analyses were
      performed using GraphPad software. Fisher exact test was performed to identify
      risk factors associated with greater morbidity. RESULTS: Of all patients, 26
      (35%) were identified as those habitually using tobacco product and 48 (64%) were
      identified as nonusers of tobacco product. Moreover, 10 patients (14%) had other
      risk factors for atherosclerotic disease and 64 patients (86%) did not have other
      risk factors for atherosclerosis. Mean (SD) time to reconstruction was 4.74 (1.3)
      days (range, 3-8 days). Of all defects, 34 (46%) were reconstructed using
      adipocutaneous flaps and 40 (54%) were reconstructed using fasciocutaneous flaps.
      The most frequent complication was partial flap loss or superficial epidermolysis
      4 (5.4%). Fisher exact test was performed, showing that patients who used tobacco
      product (cigarette smokers) and had other risk factors for atherosclerosis were
      significantly more at risk for complications (P < 0.001). CONCLUSIONS: In this
      retrospective review, those patients who had a positive history of tobacco use at
      the time of injury and those with risk factors for atherosclerosis had a
      significantly increased risk of flap complications. Although this is not
      surprising given the vasoconstrictive effects of nicotine and the impaired blood
      flow to the lower extremity in patients with atherosclerosis, this study will
      allow the surgeon to better counsel patients who have a history of tobacco use
      through complex reconstruction of the lower extremity. This analysis is a
      preliminary investigation into the safety and efficacy of the ALT fasciocutaneous
      or adipocutaneous flap to reconstruct high-energy open fractures of the lower
      extremity.

PMID- 22868330
TI  - A new dual functional sensor: highly selective colorimetric chemosensor for Fe3+
      and fluorescent sensor for Mg2+.
AB  - A new artificial receptor 1 was synthesized for the detection of Fe(3+) and
      Mg(2+) in solution as a colorimetric and fluorescent sensor, respectively. The
      sensor exhibited highly selective and sensitive recognition towards Fe(3+) in
      CH(3)CN via color change from colorless to brown. Also it showed a significant
      fluorescence enhancement (70-fold) towards Mg(2+) in the mixture of solution
      CH(3)CN/H(2)O (8:2, v/v). The selectivity of either Fe(3+) or Mg(2+) was not
      interfered by the presence of other metal ions such as Cr(3+), Mn(2+), Co(3+),
      Ni(2+), Cu(2+), Ag(+), Cd(2+), Pb(2+), Ca(2+) and K(+) ions.

PMID- 22868331
TI  - Theoretical calculation (DFT), Raman and surface-enhanced Raman scattering (SERS)
      study of ponceau 4R.
AB  - Ponceau 4R is used as a coloring agent in many different products, such as food,
      drinks, medicines, cosmetics and tobacco. However, ponceau 4R also shows
      carcinogenic, teratogenic and mutagenic behavior in high doses. In this work,
      standard Raman, theoretical Raman and surface-enhanced Raman scattering (SERS)
      spectra have been used to investigate ponceau 4R. More specifically, density
      functional theory (DFT) calculations have been used to calculate the optimized
      Raman spectrum of ponceau 4R at the B3LYP/6-31G(d) level. This has provided a
      better understanding of the optimized geometry and vibrational frequencies of
      this dye. In addition, the experimental spectrum of ponceau 4R has been compared
      with the theoretical spectrum; good agreement was obtained. Finally, it has shown
      that using SERS the detection limit of the ponceau 4R solution can be as low as 5
      MUg/mL. This has been achieved by SERS measurements of ponceau 4R on a substrate
      of gold nanoparticles. The SERS peaks at 1030, 1236, 1356 and 1502 cm(-1) were
      chosen as index for semi-quantitative analysis, showing that the SERS technique
      provided a useful ultrasensitive method for the detection of ponceau 4R.

PMID- 22868332
TI  - Identification of Jiangxi wines by three-dimensional fluorescence fingerprints.
AB  - A new assay of identifying wines was developed based on fingerprints of three
      dimensional fluorescence spectra, and 30 samples from different manufacturers
      were analyzed. The techniques of principal component analysis (PCA) and
      hierarchical cluster analysis (HCA) were used to differentiate and evaluate the
      character parameters of wines' three-dimensional fluorescence spectra. At the
      same time, the back-propagation network (BPN) was applied to predict the
      attribution of unknown samples. The results of PCA and HCA showed that there was
      definite different information among the wine samples from different
      manufacturers. It was promising that the method could be applied to distinguish
      wine samples produced by different manufacturers. The proposed method could
      provide the criterion for the quality control of wines.

PMID- 22868333
TI  - Assessment of the molecular structure of the borate mineral sakhaite
      Ca12Mg4(BO3)7(CO3)4Cl(OH)2.H2O using vibrational spectroscopy.
AB  - The structure of the borate mineral sakhaite
      Ca(12)Mg(4)(BO(3))(7)(CO(3))(4)Cl(OH)(2).H(2)O, a borate-carbonate of calcium and
      magnesium has been assessed using vibrational spectroscopy. Assignment of bands
      is undertaken by comparison with the data from other published results. Intense
      Raman band at 1134 cm(-1) with a shoulder at 1123 cm(-1) is assigned to the
      CO(3)(2-) symmetric stretching mode. The Raman spectrum displays bands at 1479,
      1524 and 1560 cm(-1) which are assigned to the CO(3)(2-) antisymmetric stretching
      vibrations. The observation of multiple carbonate stretching bands supports the
      concept that the carbonate units are non-equivalent. The Raman band at 968 cm(-1)
      with a shoulder at 950 cm(-1) is assigned to the symmetric stretching mode of
      trigonal boron. Raman bands at 627 and 651 cm(-1) are assigned to the out-of
      plane bending modes of trigonal and tetrahedral boron. Raman spectroscopy coupled
      with infrared spectroscopy enables the molecular structure of the mineral
      sakhaite to be assessed.

PMID- 22868334
TI  - FT-IR, FT-Raman, SERS and computational study of 5-ethylsulphonyl-2-(o
      chlorobenzyl)benzoxazole.
AB  - FT-IR, FT-Raman and surface-enhanced Raman scattering spectra of 5-ethylsulphonyl
      2-(o-chlorobenzyl)benzoxazole were recorded and analyzed. The vibrational
      wavenumbers were examined theoretically using the Gaussian09 set of quantum
      chemistry codes, and the normal modes were assigned by potential energy
      distribution calculations. The presence of CH(2), SO(2) and CH(3) modes in the
      SERS spectrum indicates the nearness of the methyl group to the metal surface
      which affects the orientation and metal molecule interaction. The synthesis, NMR
      spectra and antibacterial properties are reported. The title compound shows more
      inhibitory effect against Pseudomonas aeruginosa than ampicillin and found to be
      more potent against Klebsiella pneumoniae and drug-resistant Bacillus subtilis
      than the other microorganisms. A computation of the first hyperpolarizability
      indicates that the compound may be a good candidate as a NLO material. The RMS
      errors of the observed Raman and IR bands are found to be 30.93, 29.77 for HF and
      9.57, 6.75 for DFT methods, respectively.

PMID- 22868335
TI  - EPR and photoluminescence properties of Mn2+ doped CdS nanoparticles synthesized
      via co-precipitation method.
AB  - The structural properties of Mn doped CdS (Mn:CdS) nanoparticles (NPs) are
      studied using X-ray diffraction (XRD), Transmission electron microscopy (TEM),
      Ultraviolet-visible (UV-vis), Photoluminescence (PL), Raman and Electron
      paramagnetic resonance (EPR) spectroscopy. XRD analysis shows the nanostructure
      with 2-4 nm of average crystallite size. The planes (110), (103) and (112) in XRD
      pattern distinguish the wurtzite structure of the Mn:CdS NPs. The intensity of
      the plane (102) increases as the doping concentration of Mn(2+) increases. UV-vis
      absorption spectra show blue shift as compared to bulk CdS. The optical band gap
      energy of Mn(2+) (0, 0.35, 0.70 and 1.35 at.%) doped CdS NPs corresponding to
      absorption edge are found to be 5.29, 5.28, 5.25 and 5.21 eV, respectively. The
      intensity of luminescence is changing with the concentration of Mn(2+) doped in
      CdS NPs. Raman spectra show blue shift in fundamental optical phonon mode (1LO)
      as well as second optical phonon mode (2LO) as compared to bulk CdS. The
      intensity ratio of the 2LO to 1LO modes slightly decreases as Mn(2+)
      concentration increases. EPR shows the existence of Mn(2+) with different local
      structures in CdS nanoparticles. The values of spectroscopic splitting factor (g)
      and hyperfine interaction constant (A) decrease as Mn(2+) concentration increases
      in CdS NPs.

PMID- 22868336
TI  - Vibrational analysis and valence force field for nitrotoluenes, dimethylanilines
      and some substituted methylbenzenes.
AB  - The Fourier transform infrared (FTIR) and Raman spectra of 2-amino-4
      nitrotoluene; 2-amino-5-nitrotoluene; 2,4-dimethylaniline; 2,5-dimethylaniline;
      2,6-dimethylaniline; 1,2,4-trimethylbenzene; 1,3,5-trimethylbenzene and
      pentamethylbenzene have been recorded in the range 4000-400 cm(-1) and 4000-30
      cm(-1), respectively. A normal coordinate analysis was carried out for both in
      plane and out-of-plane vibrations of these molecules using an 81-parameter
      modified valence force field. The force constants were refined using 369
      frequencies of eight molecules in the overlay least-squares technique. The
      reliability of the force constants was tested by making a zero-order calculation
      for both in-plane and out-of-plane vibrations for five related molecules. The
      potential energy distributions and eigen vectors calculated in the process were
      used to make unambiguous vibrational assignments of all the fundamentals.

PMID- 22868337
TI  - Global air quality and climate.
AB  - Emissions of air pollutants and their precursors determine regional air quality
      and can alter climate. Climate change can perturb the long-range transport,
      chemical processing, and local meteorology that influence air pollution. We
      review the implications of projected changes in methane (CH(4)), ozone precursors
      (O(3)), and aerosols for climate (expressed in terms of the radiative forcing
      metric or changes in global surface temperature) and hemispheric-to-continental
      scale air quality. Reducing the O(3) precursor CH(4) would slow near-term warming
      by decreasing both CH(4) and tropospheric O(3). Uncertainty remains as to the net
      climate forcing from anthropogenic nitrogen oxide (NO(x)) emissions, which
      increase tropospheric O(3) (warming) but also increase aerosols and decrease
      CH(4) (both cooling). Anthropogenic emissions of carbon monoxide (CO) and non
      CH(4) volatile organic compounds (NMVOC) warm by increasing both O(3) and CH(4).
      Radiative impacts from secondary organic aerosols (SOA) are poorly understood.
      Black carbon emission controls, by reducing the absorption of sunlight in the
      atmosphere and on snow and ice, have the potential to slow near-term warming, but
      uncertainties in coincident emissions of reflective (cooling) aerosols and poorly
      constrained cloud indirect effects confound robust estimates of net climate
      impacts. Reducing sulfate and nitrate aerosols would improve air quality and
      lessen interference with the hydrologic cycle, but lead to warming. A holistic
      and balanced view is thus needed to assess how air pollution controls influence
      climate; a first step towards this goal involves estimating net climate impacts
      from individual emission sectors. Modeling and observational analyses suggest a
      warming climate degrades air quality (increasing surface O(3) and particulate
      matter) in many populated regions, including during pollution episodes. Prior
      Intergovernmental Panel on Climate Change (IPCC) scenarios (SRES) allowed
      unconstrained growth, whereas the Representative Concentration Pathway (RCP)
      scenarios assume uniformly an aggressive reduction, of air pollutant emissions.
      New estimates from the current generation of chemistry-climate models with RCP
      emissions thus project improved air quality over the next century relative to
      those using the IPCC SRES scenarios. These two sets of projections likely bracket
      possible futures. We find that uncertainty in emission-driven changes in air
      quality is generally greater than uncertainty in climate-driven changes.
      Confidence in air quality projections is limited by the reliability of
      anthropogenic emission trajectories and the uncertainties in regional climate
      responses, feedbacks with the terrestrial biosphere, and oxidation pathways
      affecting O(3) and SOA.

PMID- 22868338
TI  - A microfluidic microbial fuel cell array that supports long-term multiplexed
      analyses of electricigens.
AB  - Microbial fuel cells (MFCs) are green energy technologies that exploit microbial
      metabolism to generate electricity. The widespread implementation of MFC
      technologies has been stymied by their high cost and limited power. MFC arrays in
      which device configurations or microbial consortia can be screened have generated
      significant interest because of their potential for defining aspects that will
      improve performance featuring high throughput characteristics. However, current
      miniature MFCs and MFC array systems do not support long-term studies that mimic
      field conditions, and hence, have limitations in fully characterizing and
      understanding MFC performances in varieties of conditions. Here, we describe an
      MFC array device that incorporates microfluidic technology to enable continuous
      long-term analysis of MFC performance at high throughput utilizing periodic
      anolyte/catholyte replenishment. The system showed 360% higher power output and
      700% longer operating time when compared to MFC arrays without catholyte
      replenishment. We further demonstrate the utility of the system by reporting its
      successful use in screening microbial consortia collected from geographically
      diverse environments for communities that support enhanced MFC performance. Taken
      together, this work demonstrates that anolyte/catholyte replenishment can
      significantly improve the long-term performance of microfabricated MFC arrays,
      and support the characterization of diverse microbial consortia.

PMID- 22868340
TI  - The efficacy and toxicity of S-1 and cisplatin as first-line chemotherapy in
      recurrent or metastatic head and neck squamous cell carcinoma.
AB  - PURPOSE: To assess the clinical activity and toxicity of a combination
      chemotherapy regimen of S-1 and cisplatin in patients with recurrent and/or
      metastatic head and neck squamous cell carcinoma (HNSCC) in a retrospective
      study. METHODS: A total of 49 patients were treated in an outpatient setting with
      S-1 80 mg/m(2) on days 1-14 and with cisplatin 70 mg/m(2) on day 1 every 3 weeks
      for a maximum of six cycles as a first-line palliative chemotherapy. Patients who
      achieved complete response (CR), partial response (PR) or stable disease (SD)
      after six cycles received S-1 monotherapy as a maintenance therapy. RESULTS: The
      median patient age was 55 years (range 33-79), 89.8 % were male, and the Eastern
      Cooperative Oncology Group performance status distribution was 0/1/2 (20.4 %/73.5
      %/6.1 %). Of the 43 evaluable patients, 2 (4.1 %) achieved CR and 20 (40.8 %) had
      a PR, for an overall response rate of 44.9 %. Thirteen patients (26.6 %) had SD.
      The median number of chemotherapy treatments was 4 (range 1-18). Nine patients
      received maintenance S-1 monotherapy after six cycles of combination
      chemotherapy. With a mean 10.5 months (range 1.3-25.1) of follow-up, the median
      progression-free and overall survival were 4.5 (95 % CI, 3.7-5.3 months) and 10.8
      months (95 % CI, 5.9-15.6 months), respectively. The main grade 3-4 toxicities
      were neutropenia (37 %), anemia (16 %) and general weakness (8 %). Other
      toxicities, including nausea/vomiting, mucositis and neuropathy, were mostly
      grade 1-2 and easily manageable. CONCLUSIONS: The combination of S-1/cisplatin
      therapy had a favorable efficacy with manageable toxicity as a first-line
      chemotherapy regimen for advanced head and neck squamous cell carcinoma patients.

PMID- 22868341
TI  - Phase I trial of sunitinib and gemcitabine in patients with advanced solid
      tumors.
AB  - PURPOSE: Combining cytotoxic agents with bevacizumab has yielded significant
      benefits in a number of solid tumors. Combining small-molecule kinase inhibitors
      of VEGFR with chemotherapy has yet to demonstrate clinical benefit. The dose,
      schedule and agents used may be critical to the development of this combinatorial
      therapy. METHODS: We performed a phase I trial of sunitinib and gemcitabine in
      patients with advanced solid tumor malignancies based on strong preclinical
      rationale. RESULTS: Two different MTDs were determined. The schedule of
      gemcitabine 800 mg/m(2) on days 1, 8, 15 and sunitinib 25 mg daily was considered
      to be a MTD. However, omission of day 15 gemcitabine was common, and thus, a
      second MTD of gemcitabine of 675 mg/m(2) on days 1 and 8 with sunitinib 25 mg
      daily was determined to be the recommended phase II dose. Grade 4 neutropenia and
      thrombocytopenia occurred in 33 and 6 %, respectively. Grade 3/4 non
      hematological toxicities were uncommon. Four of 33 patients had a partial
      response. Another 11 patients had stable disease ranging from 3 to 36 months.
      Thus, the recommended phase II dose of this combination is gemcitabine 675
      mg/m(2) on days 1 and 8 on an every 21-day schedule along with sunitinib 25 mg
      continuous daily. CONCLUSIONS: This combination is well-tolerated and has
      significant clinical activity.

PMID- 22868342
TI  - Temporal and spatial trends of perfluoroalkyl substances in liver of roe deer
      (Capreolus capreolus).
AB  - For more than 50 years perfluoroalkyl substances (PFASs) have found worldwide
      industrial and household uses. Some PFASs are presumed to be persistent and
      bioaccumulative. Roe deer (Capreolus capreolus) are thought to be a suitable
      bioindicator for the accumulation of organic xenobiotics. Due to the ubiquitous
      nature of PFASs in the environment a retrospective study on temporal trends was
      carried out. A total of 110 deer liver pools collected from 1989 to 2010 in
      Germany were analyzed for their levels of PFASs. The highest concentrations were
      measured for perfluorooctane sulfonate (PFOS) (median 6.3 MUg/kg).
      Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and
      perfluorodecanoic acid (PFDA) were detected with median concentrations of 0.5
      MUg/kg, 1.2 MUg/kg and 0.3 MUg/kg, respectively, while concentrations of the
      other PFASs were below the limit of quantification. PFOS concentrations decreased
      significantly (r(s) = -0.741; p = <0.0001) from 9.2 MUg/kg in 2000 to 1.8 MUg/kg
      in 2010.

PMID- 22868343
TI  - Physiological response of the epiphytic lichen Evernia prunastri (L.) Ach. to
      ecologically relevant nitrogen concentrations.
AB  - This study investigated the physiological response of the epiphytic lichen
      Evernia prunastri to ecologically relevant concentrations of nitrogen compounds.
      Lichen samples were sprayed for 4 weeks either with water or 50, 150 and 500 MUM
      NH(4)Cl. The integrity of cell membranes and chlorophyll a fluorescence emission
      (F(V)/F(M) and PI(ABS)) were analyzed. No membrane damage occurred after the
      exposure period. F(V)/F(M), a classical fluorescence indicator, decreased during
      the second week of treatment with 500 MUM NH(4)Cl and the third week with 50 and
      150 MUM NH(4)Cl. PI(ABS), an overall index of the photosynthetic performance, was
      more sensitive and decreased already during the first week with 500 MUM NH(4)Cl
      and the second week with 150 MUM NH(4)Cl. Since E. prunastri has been exposed to
      ammonium loads corresponding to real environmental conditions, these findings
      open the way to an effective use of this species as early indicators of
      environmental nitrogen excess.

PMID- 22868344
TI  - The long-term impact of urbanization on nitrogen patterns and dynamics in
      Shanghai, China.
AB  - Urbanization is an important process that alters the regional and global nitrogen
      biogeochemistry. In this study, we test how long-term urbanization (1952-2004)
      affects the nitrogen flows, emissions and drivers in the Greater Shanghai Area
      (GSA) based on the coupled human and natural systems (CHANS) approach. Results
      show that: (1) total nitrogen input to the GSA increased from 57.7 to 587.9 Gg N
      yr(-1) during the period 1952-2004, mainly attributing to fossil fuel combustion
      (43%), Haber-Bosch nitrogen fixation (31%), and food/feed import (26%); (2) per
      capita nitrogen input increased from 13.5 to 45.7 kg N yr(-1), while per gross
      domestic product (GDP) nitrogen input reduced from 22.2 to 0.9 g N per Chinese
      Yuan, decoupling of nitrogen with GDP; (3) emissions of reactive nitrogen to the
      environment transformed from agriculture dominated to industry and human living
      dominated, especially for air pollution. This study provides decision-makers a
      novel view of nitrogen management.

PMID- 22868345
TI  - Summer-winter concentrations and gas-particle partitioning of short chain
      chlorinated paraffins in the atmosphere of an urban setting.
AB  - Short chain chlorinated paraffins (SCCPs) are semi-volatile chemicals that are
      considered persistent in the environment, potential toxic and subject to long
      range transport. This study investigates the concentrations and gas-particle
      partitioning of SCCPs at an urban site in Beijing during summer and wintertime.
      The total atmospheric SCCP levels ranged 1.9-33.0 ng/m(3) during wintertime.
      Significantly higher levels were found during the summer (range 112-332 ng/m(3)).
      The average fraction of total SCCPs in the particle phase (phi) was 0.67 during
      wintertime but decreased significantly during the summer (phi = 0.06). The ten
      and eleven carbon chain homologues with five to eight chlorine atoms were the
      predominant SCCP formula groups in air. Significant linear correlations were
      found between the gas-particle partition coefficients and the predicted subcooled
      vapor pressures and octanol-air partition coefficients. The gas-particle
      partitioning of SCCPs was further investigated and compared with both the Junge
      Pankow adsorption and K(oa)-based absorption models.

PMID- 22868346
TI  - Physiological and molecular responses of the earthworm (Eisenia fetida) to soil
      chlortetracycline contamination.
AB  - This study aims to evaluate toxic effects of exposure to chlortetracycline (CTC)
      in soil on reproductive endpoints (juvenile counts and cocoon counts),
      biochemical responses, and genotoxic potentials of the earthworm Eisenia fetida.
      Results showed that juvenile counts and cocoon counts of the tested earthworms
      were reduced after exposure to CTC. The effective concentrations (EC(50) values)
      for juvenile and cocoon counts were 96.1 and 120.3 mg/kg, respectively. Treatment
      of earthworms with CTC significantly changed the activity of catalase (CAT),
      superoxide dismutase (SOD) and glutathione S-transferase (GST). An increase in
      malondialdehyde (MDA) indicated that CTC could cause cellular lipid peroxidation
      in the tested earthworms. The percentage of DNA in the tail of single-cell gel
      electrophoresis of coelomocytes as an indication of DNA damage increased after
      treatment with different doses of CTC, and a dose-dependent DNA damage of
      coelomocytes was found. In conclusion, CTC induces physiological responses and
      genotoxicity on earthworms.

PMID- 22868347
TI  - Anaerobic performance testing of professional soccer players 1995-2010.
AB  - PURPOSE: To compare sprint and countermovement-jump (CMJ) performance among
      competitive soccer players as a function of performance level, field position,
      and age. In addition, the authors wanted to quantify the evolution of these
      physical characteristics among professional players over a 15-y period. METHODS:
      939 athletes (22.1 +/- 4.3 y), including national-team players, tested 40-m
      sprint with electronic timing and CMJ on a force platform at the Norwegian
      Olympic Training Center between 1995 and 2010. RESULTS: National-team and 1st
      division players were faster (P < .05) than 2nd-division (1.0-1.4%), 3rd- to 5th
      division (3.0-3.8%), junior national-team (1.7-2.2%), and junior players (2.8
      3.7%). Forwards were faster than defenders (1.4%), midfielders (2.5%), and
      goalkeepers (3.2%) over 0-20 m (P < .001). Midfielders jumped ~2.0 cm lower than
      the other playing positions (P < .05). Sprinting velocity peaked in the age range
      20-28 y and declined significantly thereafter (P < .05). Players from 2006-2010
      had 1-2% faster 0-20 m and peak velocity than players from the 1995-1999 and 2000
      2005 epochs, whereas no differences in CMJ performance were observed.
      CONCLUSIONS: This study provides effect-magnitude estimates for the influence of
      performance level, position, and age on sprint and CMJ performance in soccer.
      While CMJ performance has remained stable over the time, there has been a small
      but positive development in sprinting velocity among professional players.

PMID- 22868348
TI  - Phototriggered growth of crystalline Au structures in the presence of a DNA
      surfactant complex.
AB  - A method for the preparation of complex anisotropic gold structures with
      potential uses in catalysis and photonics is presented based on the use of salmon
      sperm DNA and a photosensitizer to enable light triggered gold salt reduction.

PMID- 22868349
TI  - Prevalence, incidence and obstetric factors' impact on female urinary
      incontinence in Europe: a systematic review.
AB  - OBJECTIVES: A systematic review of the published data on the prevalence,
      incidence and risk factors of female urinary incontinence (UI) and obstetric
      treatment of UI in Europe. DATA SOURCES: Epidemiologic studies were sought via
      PubMed to identify articles published in English, French, Spanish, German and
      Italian between 2000 and September 30, 2010, in Europe. RESULTS: The prevalence
      of UI ranged from 14.1 to 68.8% and increased with increasing age. Significant
      risk factors for UI in pregnancy were maternal age >=35 years and initial body
      mass index, a family history of UI and parity. UI in women who delivered 'at
      term' ranged from 26 to 40.2%, with a remission rate of 3 months after childbirth
      of up to 86.4%. Pelvic floor muscle training may help to prevent postpartum UI in
      primiparous women without UI during pregnancy. CONCLUSION: UI definition, outcome
      measures, survey methods and validation criteria are still heterogeneous, and
      thus it is difficult to compare data and impossible to draw definite conclusions.

PMID- 22868350
TI  - Primary ligament sutures as a treatment option of knee dislocations: a meta
      analysis.
AB  - PURPOSE: Treatment of knee dislocation is still controversial. There is no
      evidence to favour ligament suture or reconstruction. Until now, no meta-analyses
      have examined suture versus reconstruction of cruciate ligaments in knee
      dislocations with respect to injury pattern and rupture classification. METHODS:
      We searched Medline, the Cochrane Controlled Trial Database, and EMBASE for
      studies on surgical treatment for 'knee dislocation' and 'multiple ligament
      injured knee'. A meta-analysis was performed using individual patient data.
      RESULTS: Nine studies including 195 patients (200 knees) with a mean age of 31.4
      (+/-13) years fulfilled the study requirements. Thirteen cases of type II
      dislocations, 63 cases of type III medial, 84 cases of type III lateral, and 40
      cases of type IV dislocations, according to Schenck's classification, were found.
      Poor or moderate results were found in 70 % of patients without surgical
      treatment of ACL or PCL (n = 27). Patients (n = 40) treated by sutures of the ACL
      and PCL demonstrated a significantly greater proportion of excellent or good
      results (40 and 37.5 %, respectively) (p < 0.001). Patients who underwent
      reconstruction of the ACL and PCL (n = 75) showed excellent or good results (28
      and 45 %, respectively). No significant difference was found when comparing
      suture versus reconstruction of the ACL and PCL (n.s.). The outcome depends
      considerably on Schenck's injury pattern classification. CONCLUSION: Conservative
      treatment after knee dislocation yields poor clinical results. Suture repair of
      cruciate ligaments can still serve as an alternative option for multiligament
      injuries of the knee and achieve good clinical results, which are comparable to
      those of ligament reconstruction. The data provided by this meta-analysis should
      be reinforced by a prospective study, in which suture repair and ligament
      reconstruction are compared. LEVEL OF EVIDENCE: IV.

PMID- 22868351
TI  - Anteroposterior and rotational stability in fixed and mobile bearing unicondylar
      knee arthroplasty: a cadaveric study using the robotic force sensor system.
AB  - PURPOSE: Different bearing designs in unicondylar knee arthroplasty (UKA) have
      been developed in order to influence the rate of polyethylene wear. Increased
      anteroposterior translation and rotation after UKA has been hypothesized due to
      changes in joint surface geometry. The mobile bearing design was expected to show
      increased anteroposterior translation compared to the fixed bearing and biconcave
      bearing design. METHODS: Six human cadaver knees were used for the tests.
      Anteroposterior and rotational knee stability was analysed in 0 degrees , 30
      degrees , 60 degrees , 90 degrees  and 120 degrees  of knee flexion using a
      robotic testing system (KR 125, KUKA Robots Augsburg, Germany). Three forces and
      moments were measured in a Cartesian coordinate system with a resolution of 1.0 N
      and 0.1 Nm. RESULTS: There was no difference between the native knees and the
      knees after UKA in AP translation and rotation in all knee flexion angles. The
      factor knee flexion angle had a significant impact on the anterior translation
      when the type of bearing was neglected (p <= 0.015). CONCLUSION: This study shows
      that the natural knee stability in AP translation and rotation can be preserved
      in UKA. The preserved knee stability in different planes after UKA underlines the
      advantage of UKA when surgery is required in osteoarthritic changes of the medial
      compartment.

PMID- 22868352
TI  - Cognitive decline and amyloid accumulation in patients with mild cognitive
      impairment.
AB  - BACKGROUND/AIMS: The relationship between baseline (11)C-Pittsburgh compound B
      ((11)C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in
      9 patients with mild cognitive impairment (MCI) who converted to Alzheimer's
      disease (AD) and 7 who remained with MCI. METHODS: (11)C-PIB PET scan was
      conducted at baseline and cognitive assessment both at baseline and at follow-up.
      To obtain quantitative regional values of (11)C-PIB uptake, automated region of
      interest analysis was done using spatially normalized parametric ratio (region-to
      cerebellar cortex) images. RESULTS: At baseline, there were statistically
      significant differences in (11)C-PIB uptake, but not in cognitive test
      performances between the converters and nonconverters. Memory and executive
      function declined only in the converters during follow-up. In the converters,
      lower baseline frontal (11)C-PIB uptake was associated with faster decline in
      verbal learning. Higher baseline uptake in the caudate nucleus was related to
      faster decline in memory consolidation, and higher temporal uptake was associated
      with decline in executive function. CONCLUSION: Higher (11)C-PIB uptake in the
      caudate nucleus and temporal lobe was related to decline in memory and executive
      functions, whereas lower frontal uptake was related to decline in verbal
      learning. The results indicate that in prodromal AD, frontal amyloid accumulation
      reaches its maximum in the MCI stage, characterized by memory problems without
      full-blown dementia.

PMID- 22868353
TI  - Selected AB4(2-/-) (A = C, Si, Ge; B = Al, Ga, In) ions: a battle between
      covalency and aromaticity, and prediction of square planar Si in SiIn4(2-/-).
AB  - CAl(4)(2-/-) (D(4h), (1)A(1g)) is a cluster ion that has been established to be
      planar, aromatic, and contain a tetracoordinate planar C atom. Valence
      isoelectronic substitution of C with Si and Ge in this cluster leads to a radical
      change of structure toward distorted pentagonal species. We find that this
      structural change goes together with the cluster acquiring partial covalency of
      bonding between Si/Ge and Al(4), facilitated by hybridization of the atomic
      orbitals (AOs). Counter intuitively, for the AAl(4)(2-/-) (A = C, Si, Ge)
      clusters, hybridization in the dopant atom is strengthened from C, to Si, and to
      Ge, even though typically AOs are more likely to hybridize if they are closer in
      energy (i.e. in earlier elements in the Periodic Table). The trend is explained
      by the better overlap of the hybrids of the heavier dopants with the orbitals of
      Al(4). From the thus understood trend, it is inferred that covalency in such
      clusters can be switched off, by varying the relative sizes of the AOs of the
      main element and the dopant. Using this mechanism, we then successfully killed
      covalency in Si, and predicted a new aromatic cluster ion containing a
      tetracoordinate square planar Si, SiIn(4)(2-/-).

PMID- 22868354
TI  - A column-switching liquid chromatography-tandem mass spectrometry method for
      quantitation of 2-cyanoethylmercapturic acid and 2-hydroxyethylmercapturic acid
      in Chinese smokers.
AB  - The acrylonitrile metabolites 2-cyanoethylmercapturic acid (CEMA) and 2
      hydroxyethylmercapturic acid (HEMA) have been determined in human urine using an
      automated column-switching procedure. A diluted sample was centrifuged just prior
      to being injected into a reusable precolumn packed with a restricted access
      material and coupled to a liquid chromatography-tandem mass spectrometry system.
      This method achieved satisfactory reproducibility and accuracy. Average intra-
      and interday variations (% relative standard deviations) ranged from 2.4 to 3.8%
      for CEMA and from 2.7 to 10.5% for HEMA. The limits of quantification were 0.003
      and 0.099ng/ml for CEMA and HEMA, respectively. It was used to study the uptake
      of acrylonitrile from smoke constituents by both nonsmokers and smokers of
      different tar yield cigarettes under ISO 3308 smoking condition. Metabolite
      concentrations in smoker urine samples were approximately 12 times higher
      compared with those in nonsmokers for CEMA and 3 times higher for HEMA. Urinary
      CEMA levels show a clear dose-response relationship with daily cigarette
      consumption and urinary cotinine. CEMA can also discriminate between smokers of
      different ISO cigarettes. Because HEMA is not specific, it is only slightly
      related to smoking and acrylonitrile exposure. The validated biomarker CEMA will
      continue to be useful for studies of acrylonitrile uptake by smokers.

PMID- 22868355
TI  - Pathophysiology of the small airways in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by a persistent
      airflow limitation that is usually progressive and associated with an enhanced
      chronic inflammatory response in the airways and the lung to noxious particles or
      gases. From a pathological point of view, COPD is characterized by two distinct
      and frequently coexisting aspects: small airway abnormalities and parenchymal
      destruction (or emphysema). When pathological changes are localized in lung
      parenchyma, they will contribute to airflow limitation by reducing the elastic
      recoil of the lung through parenchymal destruction, as well as by reducing the
      elastic load applied to the airways through destruction of alveolar attachments.
      Conversely, when pathological changes involve the small airways, they will
      contribute to airflow limitation by narrowing and obliterating the lumen and by
      actively constricting the airways, therefore increasing the resistance. In this
      article we will review the structural abnormalities in small airways and their
      relationship with the disordered pulmonary function in COPD, in the attempt to
      disentangle the mechanisms contributing to the development and progression of
      airflow limitation in smokers. We will start by describing the normal structure
      of the small airways, and then observe the main pathological alterations that
      accumulate in this site and how they parallel pulmonary function derangement.

PMID- 22868356
TI  - Transformation optofluidics for large-angle light bending and tuning.
AB  - Transformation optics is a new art of light bending by designing materials with
      spatially variable parameters for developing wave-manipulation devices. Here, we
      introduce a transformation optofluidic Y-branch splitter with large-angle bending
      and tuning based on the design of a spatially variable index. Differing from
      traditional splitters, the optofluidic splitter is achieved in an inhomogeneous
      medium by coordinate transformation. The designed bidirectional gradient index
      (GRIN) distribution can be achieved practically by the convection-diffusion
      process of liquid flowing streams. The transformation optofluidic splitter can
      achieve a much larger split angle with little bend loss than the traditional
      ones. In the experiments, a large tunable split angle up to 30 degrees  is
      achieved by tuning the flow rates, allowing optical signals to be freely
      transferred to different channels. Besides the symmetrical branch splitting,
      asymmetrical Y-branch splitting with approximately equal power splitting is also
      demonstrated by changing the composition of the liquids. The optofluidic splitter
      has high potential applications in biological, chemical and biomedical solution
      measurement and detection.

PMID- 22868357
TI  - Robot-assisted minimally invasive distal pancreatectomy is superior to the
      laparoscopic technique.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) reduces postoperative
      morbidity, hospital stay, and recovery as compared with open distal
      pancreatectomy. Technical limitations of laparoscopic surgery may limit patient
      eligibility and require conversion to open or hand-assisted surgery to maintain
      patient safety. We hypothesized that robot-assisted distal pancreatectomy (RADP)
      was superior to LDP as a result of improved surgical manipulation and
      visualization, potentially expanding the indications for minimally invasive
      pancreatectomy. METHODS: We performed a retrospective analysis of all minimally
      invasive distal pancreatectomies at University of Pittsburgh Medical Center
      between January 2004 and February 2011. We compared the perioperative outcomes,
      90-day morbidity and mortality of our first 30 RADPs to 94 consecutive historical
      control LDPs. RESULTS: Patients undergoing RADP and LDP demonstrated equivalent
      age, sex, race, American Society of Anesthesiologists' score, and tumor size.
      Postoperative length of hospital stay and rates of pancreatic fistula, blood
      transfusion, and readmission were not statistically different. Patients in the
      RADP group did not require conversion to open surgery unlike the LDP group (16%,
      P < 0.05) and had reduced risk of excessive blood loss. There were more
      pancreatic ductal adenocarcinomas approached robotically (43%) than
      laparoscopically (15%) (P < 0.05). Oncological outcomes in these cases were
      superior for the robotic-assisted group with higher rates of margin negative
      resection and improved lymph node yield for both benign and malignant lesions (P
      < 0.0001). CONCLUSIONS: RADPs were equivalent to LDPs in nearly all measures of
      outcome and safety but significantly reduced the risk of conversion to open
      resection, despite a statistically greater probability of malignancy in the
      robotic cohort. We concluded that robotic assistance may broaden indications for
      minimally invasive pancreatectomy.

PMID- 22868358
TI  - Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma
      influences postoperative survival in patients with preoperative low HBV-DNA
      levels.
AB  - OBJECTIVE: This study aimed to clarify the incidence of hepatitis B virus (HBV)
      reactivation and its significance on long-term survival after partial hepatectomy
      in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative
      low HBV-DNA level of less than 2000 IU/mL. BACKGROUND: HBV reactivation is a
      frequent complication of systemic chemotherapy in hepatitis B surface antigen
      positive patients. Surgery and anesthesia result in a generalized state of
      immunosuppression in the immediate postoperative period. Data on HBV reactivation
      and its significance after partial hepatectomy are unclear. PATIENTS AND METHODS:
      Consecutive patients from January 2006 to December 2007 were retrospectively
      studied. RESULTS: HBV reactivation happened in 19.1% of patients in 1 year. There
      were 28 patients whose HBV reactivation was detected after the diagnosis of HCC
      recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity,
      preoperative HBV-DNA above the lower limit of quantification (>=200 IU/mL), Ishak
      inflammation score of greater than 3, preoperative transarterial
      chemoembolization (TACE), operation time of more than 180 minutes, blood
      transfusion, and without prophylactic antiviral therapy were significantly
      associated with an increased risk of HBV reactivation. HBV reactivation
      negatively influenced postoperative hepatic functions. The posthepatectomy liver
      failure rate in patients with HBV reactivation was significantly higher than in
      those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free
      survival (DFS) rate and overall survival (OS) rates after resection in patients
      with HBV reactivation were significantly lower than those without reactivation
      (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg
      positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score,
      preoperative TACE, long operation time, and blood transfusion were independent
      risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a
      protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL
      or more, tumor diameter greater than 5 cm, presence of satellite nodules,
      presence of portal vein tumor thrombus, blood transfusion, and resection margin
      less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200
      IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater
      than 5 cm, the presence of satellite nodules, the presence of portal vein tumor
      thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy,
      and HBV reactivation were independent risk factors for OS. CONCLUSIONS: HBV
      reactivation was common after partial hepatectomy for HBV-related HCC with a
      preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic
      antiviral treatment should be given before partial hepatectomy.

PMID- 22868359
TI  - Shaping a modern academic department of surgery: honoring the past; focusing on
      the future.

PMID- 22868360
TI  - Failure-to-pursue rescue: explaining excess mortality in elderly emergency
      general surgical patients with preexisting "do-not-resuscitate" orders.
AB  - OBJECTIVE: To describe the outcomes of elderly patients with do-not-resuscitate
      (DNR) status who undergo emergency general surgery and to improve understanding
      of the relationship between preoperative DNR status and postoperative mortality.
      BACKGROUND: Preoperative DNR status has previously been shown to predict
      increased postoperative mortality, although the reasons for this association are
      not well understood. METHODS: Patients 65 years or older undergoing emergency
      operation for 1 of 10 common general surgical diagnoses were extracted from the
      2005-2010 National Surgical Quality Improvement database. Propensity score
      techniques were used to match patients with and without preoperative DNR orders
      on indication for procedure, patient demographics, comorbid disease burden, acute
      physical status at the time of operation, and procedure complexity. The
      postoperative outcomes of this matched cohort were then compared. RESULTS: A
      total of 25,558 patients were included for analysis (DNR, n =1061; non-DNR, n
      =24,497). DNR patients seemed to be more acutely and chronically ill than non-DNR
      patients in the overall study sample but did not seem to be treated less
      aggressively before or during their operations. Propensity-matching techniques
      resulted in the creation of a cohort of DNR and non-DNR patients who were well
      matched for all preoperative and intraoperative variables. DNR patients from the
      matched cohort had a significantly higher postoperative mortality rate than non
      DNR patients (36.9% vs 22.3%, P < 0.0001) despite having a similar rate of major
      postoperative complications (42.1% vs 40.2%, P = 0.38). DNR patients in the
      propensity-matched cohort were much less likely to undergo reoperation (8.3% vs
      12.0%, P = 0.006) than non-DNR patients and were significantly more likely to die
      in the setting of a major postoperative complication (56.7% vs 41.4%, P = 0.001).
      CONCLUSIONS: Emergency general surgery in elderly patients with preoperative DNR
      orders is associated with significant rates of postoperative morbidity and
      mortality. One reason for the excess mortality in these patients, relative to
      otherwise similar patients who do not have preoperative DNR orders, may be their
      greater reluctance to pursue aggressive management of major complications in the
      postoperative period.

PMID- 22868361
TI  - Laparoscopic colon resection trends in utilization and rate of conversion to open
      procedure: a national database review of academic medical centers.
AB  - OBJECTIVE: This study aims to examine trends of utilization and rates of
      conversion to open procedure for patients undergoing laparoscopic colon
      resections (LCR). METHODS: This study is a national database review of academic
      medical centers and a retrospective analysis utilizing the University
      HealthSystem Consortium administrative database-an alliance of more than 300
      academic and affiliate hospitals. RESULTS: A total of 85,712 patients underwent
      colon resections between October 2008 and December 2011. LCR was attempted in
      36,228 patients (42.2%), with 5751 patients (15.8%) requiring conversion to an
      open procedure. There was a trend toward increasing utilization of LCR from 37.5%
      in 2008 to 44.1% in 2011. Attempted laparoscopic transverse colectomy had the
      highest rate of conversion (20.8%), followed by left (20.7%), right (15.6%), and
      sigmoid (14.3%) colon resections. The rate of utilization was highest in the Mid
      Atlantic region (50.5%) and in medium- to large-sized hospitals (47.0%
      49.0%).Multivariate logistic regression has shown that increasing age [odds ratio
      (OR) = 4.8, 95% confidence interval (CI) = 3.6-6.4], male sex (OR = 1.2, 95% CI =
      1.1-1.3), open as compared with laparoscopic approach (OR = 2.6, 95%, CI = 2.3
      3.1), and greater severity of illness category (OR = 27.1, 95% CI = 23.0-31.9)
      were all associated with increased mortality and morbidity and prolonged length
      of hospital stay. CONCLUSIONS: There is a trend of increasing utilization of LCR,
      with acceptable conversion rates, across hospitals in the United States over the
      recent years. When feasible, attempted LCR had better outcomes than open
      colectomy in the immediate perioperative period.

PMID- 22868362
TI  - Preoperative laboratory testing in patients undergoing elective, low-risk
      ambulatory surgery.
AB  - BACKGROUND: Routine preoperative laboratory testing for ambulatory surgery is not
      recommended. METHODS: Patients who underwent elective hernia repair (N = 73,596)
      were identified from the National Surgical Quality Improvement Program (NSQIP)
      database (2005-2010). Patterns of preoperative testing were examined.
      Multivariate analyses were used to identify factors associated with testing and
      postoperative complications. RESULTS: A total of 46,977 (63.8%) patients
      underwent testing, with at least one abnormal test recorded in 61.6% of patients.
      In patients with no NSQIP comorbidities (N = 25,149) and no clear indication for
      testing, 54% received at least one test. In addition, 15.3% of tested patients
      underwent laboratory testing the day of the operation. In this group, surgery was
      done despite abnormal results in 61.6% of same day tests. In multivariate
      analyses, testing was associated with older age, ASA (American Society of
      Anesthesiologists) class >1, hypertension, ascites, bleeding disorders, systemic
      steroids, and laparoscopic procedures. Major complications (reintubation,
      pulmonary embolus, stroke, renal failure, coma, cardiac arrest, myocardial
      infarction, septic shock, bleeding, or death) occurred in 0.3% of patients. After
      adjusting for patient and procedure characteristics, neither testing nor abnormal
      results were associated with postoperative complications. CONCLUSIONS:
      Preoperative testing is overused in patients undergoing low-risk, ambulatory
      surgery. Neither testing nor abnormal results were associated with postoperative
      outcomes. On the basis of high rates of testing in healthy patients, physician
      and/or facility preference and not only patient condition currently dictate use.
      Involvement from surgical societies is necessary to establish guidelines for
      preoperative testing.

PMID- 22868363
TI  - Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison
      syndrome.
AB  - OBJECTIVES: To address the value of surgery in patients with sporadic Zollinger
      Ellison syndrome (ZES) with negative imaging studies. BACKGROUND: Medical control
      of acid hypersecretion in patients with sporadic ZES is highly effective. This
      has led to these patients frequently not being sent to surgery, especially if
      preoperative imaging studies are negative, due, in large part, to existence of
      almost no data on the success of surgery in this group. METHODS: Fifty-eight
      prospectively studied patients with sporadic ZES (17% of total studied) had
      negative imaging studies, and their surgical outcome was compared with 117
      patients with positive imaging results. RESULTS: Thirty-five patients had
      negative imaging studies in the pre-somatostatin receptor scintigraphy (SRS) era,
      and 23 patients in the post-SRS era. Patients with negative imaging studies had
      long disease histories before surgery [mean +/- SEM (from onset) = 7.9 +/- 1
      [range, -0.25 to 35 years]) and 25% were followed for 2 or more years from
      diagnosis. At surgery, gastrinoma was found in 57 of 58 patients (98%). Tumors
      were small (mean = 0.8 cm, 60% <1 cm). The most common primary sites were
      duodenal 64%, pancreatic 17%, and lymph node (10%). Fifty percent had a primary
      only, 41% primary + lymph node, and 7% had liver metastases. Thirty-five of 58
      patients (60%) were cured immediately postoperatively, and at last follow-up
      [mean = -9.4 years; range, 0.2-22 years], 27 patients (46%) remained cured.
      During follow-up, 3 patients died, each had liver metastases at surgery. In
      comparison to positive imaging patients, those with negative imaging studies had
      lower preoperative fasting gastrin levels; had a longer delay before surgery;
      more frequently had a small duodenal tumor; less frequently had a pancreatic
      tumor, multiple tumors, or developed a new lesion postoperatively; and had a
      longer survival. CONCLUSIONS: Sporadic ZES patients with negative imaging studies
      are not rare even in the post-SRS period. An experienced surgeon can find
      gastrinoma in almost every patient (98%) and nearly one half (46%) are cured, a
      rate similar to patients with positive imaging findings. Because liver metastases
      were found in 7%, which may have been caused by a long delay in surgery and all
      the disease-related deaths occurred in this group, surgery should be routinely
      undertaken early in ZES patients despite negative imaging studies.

PMID- 22868365
TI  - Factors associated with local-regional recurrence after a negative sentinel node
      dissection: results of the ACOSOG Z0010 trial.
AB  - OBJECTIVE: To determine factors important in local-regional recurrence (LRR) in
      patients with negative sentinel lymph nodes (SLNs) by hematoxylin and eosin (H&E)
      staining. BACKGROUND: Z0010 was a prospective multicenter trial initiated in 1999
      by the American College of Surgeons Oncology Group to evaluate occult disease in
      SLNs and bone marrow of early-stage breast cancer patients. Participants included
      women with biopsy-proven T1-2 breast cancer with clinically negative nodes,
      planned for lumpectomy and whole breast irradiation. METHODS: Women with clinical
      T1-2,N0,M0 disease underwent lumpectomy and SLN dissection. There was no axillary
      specific treatment for H&E-negative SLNs, and clinicians were blinded to
      immunohistochemistry results. Systemic therapy was based on primary tumor
      factors. Univariable and multivariable analyses were performed to determine
      clinicopathologic factors associated with LRR. RESULTS: Of 5119 patients, 3904
      (76.3%) had H&E-negative SLNs. Median age was 57 years (range 23-95). At median
      follow-up of 8.4 years, there were 127 local, 20 regional, and 134 distant
      recurrences. Factors associated with local-regional recurrence were hormone
      receptor-negative disease (P = 0.0004) and younger age (P = 0.047). In competing
      risk-regression models, hormone receptor-positive disease and use of chemotherapy
      were associated with reduction in local-regional recurrence. When local
      recurrence was included in the model as a time-dependent variable, older age, T2
      disease, high tumor grade, and local recurrence were associated with reduced
      overall survival. CONCLUSIONS: Local-regional recurrences are rare in early-stage
      breast cancer patients with H&E-negative SLNs. Younger age and hormone receptor
      negative disease are associated with higher event rates, and local recurrence is
      associated with reduced overall survival.

PMID- 22868366
TI  - Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with
      higher mortality in trauma.
AB  - OBJECTIVES: To identify all trauma patients with diabetes and compare diabetic
      hyperglycemia (DH) patients with those with stress-induced hyperglycemia (SIH).
      BACKGROUND: SIH has been shown to result in worse outcomes after trauma. The
      presence of diabetes mellitus (DM) or occult DM within the cohort confounded
      previous studies. We identified 2 distinct populations of trauma patients with
      SIH or DH to determine the impact of hyperglycemia on these 2 groups. METHODS:
      Admission glycosylated hemoglobin (HbA1c), glucose levels, and comorbidity data
      were collected over a 2-year period. DM was determined by patient history or
      admission HbA1c 6.5% or more. SIH was determined by absence of DM and admission
      glucose 200 mg/dL or more. Cox proportional hazards models [adjusted for age,
      sex, injury mechanism, and injury severity score] were used to calculate risk
      ratios (RRs) and associated 95% confidence intervals (CIs) for outcomes of
      interest. RESULTS: During the study period, 6852 trauma patients were evaluated,
      and 5117 had available glucose, HbA1c, and comorbidity data. Patients with SIH
      had an over twofold increase in mortality risk (RR 2.41, 95% CI 1.81-3.23), and
      patients with DH had a nonsignificant, near-50% increase in mortality risk (RR
      1.47, 95% CI 0.92-2.36). Risk of pneumonia was similarly higher for both the DH
      (RR 1.49, 95% CI 1.03-2.17) and the SIH (RR 1.44, 95% CI 1.08-1.93). CONCLUSIONS:
      DM is common in patients with hyperglycemia after trauma. As opposed to DH, SIH
      is associated with higher mortality after trauma. Further research is warranted
      to identify mechanisms causing hyperglycemia and subsequent worse outcomes after
      trauma.

PMID- 22868367
TI  - Thoracoscopic lobectomy has increasing benefit in patients with poor pulmonary
      function: a Society of Thoracic Surgeons Database analysis.
AB  - OBJECTIVE: Using a national database, we asked whether video-assisted
      thoracoscopic surgery (VATS) lobectomy is beneficial in high-risk pulmonary
      patients. BACKGROUND: Single-institution series demonstrated benefit of VATS
      lobectomy over lobectomy via thoracotomy in poor pulmonary function patients
      [FEV1 (forced expiratory volume in 1 second) or DLCO (diffusion capacity of the
      lung to carbon monoxide) <60% predicted]. METHODS: The STS General Thoracic
      Database was queried for patients having undergone lobectomy by either
      thoracotomy or VATS between 2000 and 2010. Postoperative pulmonary complications
      included those defined by the STS database. RESULTS: In the STS database, 12,970
      patients underwent lobectomy (thoracotomy, n = 8439; VATS, n = 4531) and met
      inclusion criteria. The overall rate of pulmonary complications was 21.7%
      (1832/8439) and 17.8% (806/4531) in patients undergoing lobectomy with
      thoracotomy and VATS, respectively (P < 0.0001). In a multivariable model of
      pulmonary complications, thoracotomy approach (OR = 1.25, P < 0.001), decreasing
      FEV1% predicted (OR = 1.01 per unit, P < 0.001) and DLCO% predicted (OR = 1.01
      per unit, P < 0.001), and increasing age (1.02 per year, P < 0.001) independently
      predicted pulmonary complications. When examining pulmonary complications in
      patients with FEV1 less than 60% predicted, thoracotomy patients have markedly
      increased pulmonary complications when compared with VATS patients (P = 0.023).
      No significant difference is noted with FEV1 more than 60% predicted.
      CONCLUSIONS: Poor pulmonary function predicts respiratory complications
      regardless of approach. Respiratory complications increase at a significantly
      greater rate in lobectomy patients with poor pulmonary function after thoracotomy
      compared with VATS. Planned surgical approach should be considered while
      determining whether a high-risk patient is an appropriate resection candidate.

PMID- 22868368
TI  - Long-term survival, nutritional autonomy, and quality of life after intestinal
      and multivisceral transplantation.
AB  - OBJECTIVE: To assess long-term survival, graft function, and health-related
      quality of life (QOL) after visceral transplantation. BACKGROUND: Despite
      continual improvement in early survival, the long-term therapeutic efficacy of
      visceral transplantation has yet to be defined. METHODS: A prospective cross
      sectional study was performed on 227 visceral allograft recipients who survived
      beyond the 5-year milestone. Clinical data were used to assess outcome including
      graft function and long-term survival predictors. The socioeconomic milestones
      and QOL measures were assessed by clinical evaluation, professional consultation,
      and validated QOL inventory. RESULTS: Of 376 recipients, 227 survived beyond 5
      years, with conditional survival of 75% at 10 years and 61% at 15 years. With a
      mean follow-up of 10 +/- 4 years, 177 (92 adults, 85 children) are alive, with
      118 (67%) recipients 18 years or older. Nonfunctional social support and
      noninclusion of the liver in the visceral allograft are the most significant
      survival risk factors. Nutritional autonomy was achievable in 160 (90%)
      survivors, with current serum albumin level of 3.7 +/- 0.5 gm/dL and body mass
      index of 25 +/- 6 kg/m(2). Despite coexistence or development of neuropsychiatric
      disorders, most survivors were reintegrated to society with self-sustained
      socioeconomic status. In parallel, most of the psychological, emotional, and
      social QOL measures significantly (P < 0.05) improved after transplantation.
      Current morbidities with potential impact on global health included dysmotility
      (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with
      significantly (P < 0.05) higher incidence among adult recipients. CONCLUSIONS:
      With new tactics to further improve long-term survival including social support
      measures, visceral transplantation has achieved excellent nutritional autonomy
      and good QOL.

PMID- 22868369
TI  - Associating liver partition and portal vein ligation for staged hepatectomy
      (ALPPS): what is gained and what is lost?

PMID- 22868370
TI  - Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic
      triple-negative breast cancer.
AB  - OBJECTIVE: This study aimed to investigate the therapeutic impact of a new
      oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model
      and its potential for treating distant metastatic disease. BACKGROUND: TNBCs are
      aggressive tumors associated with a high metastatic rate. Their lack of targets
      for hormonal/biological therapy presents significant clinical challenges and a
      dire need for novel therapies. METHODS: GLV-1h153, a replication-competent
      vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral
      replication were determined. Intratumoral (IT) or intravenous (IV) injection of
      GLV-1h153 (1 * 10(7) plaque-forming units) or phosphate buffered saline was
      tested in an orthotopic murine model, which reliably produces systemic
      metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain)
      were harvested 5 and 8 weeks after treatment and prepared for histopathological
      review. Demonstration of metastasis was performed using immunofluorescence and
      hematoxylin and eosin (H&E) staining. RESULTS: GLV-1h153 infected, replicated in,
      and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after
      treatment was 22 (IT), 29 (IV) versus 245 mm(3) (control; P < 0.002). Five weeks
      after treatment, all harvested lymph nodes and organs showed no evidence of
      metastatic cells. All harvested tumors showed complete response to treatment,
      with only necrosis and fibrosis on H&E staining 8 weeks after treatment.
      CONCLUSIONS: This is the first study to demonstrate that TNBCs are killed by a
      novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV
      1h153 is a promising therapeutic agent for preventing and treating metastatic
      TNBC and warrants further clinical testing in patients.

PMID- 22868371
TI  - Admission rapid thrombelastography can replace conventional coagulation tests in
      the emergency department: experience with 1974 consecutive trauma patients.
AB  - OBJECTIVE: Injury and shock lead to alterations in conventional coagulation tests
      (CCTs). Recently, rapid thrombelastography (r-TEG) has become recognized as a
      comprehensive assessment of coagulation abnormalities. We have previously shown
      that admission r-TEG results are available faster than CCTs and predict pulmonary
      embolism. We hypothesized that r-TEGs more reliably predict blood component
      transfusion than CCTs. METHODS: Consecutive patients admitted between September
      2009 and February 2011 who met the highest-level trauma activations were
      included. All had admission r-TEG and CCTs. We correlated r-TEG values [activated
      clotting time (ACT), r, k, alpha, maximal amplitude (MA), LY30] with their
      corresponding CCTs [prothrombin time (PT)/activated partial thromboplastin time
      (aPTT), international normalized ratio (INR), platelet count and fibrinogen] for
      transfusion requirements. Charges were calculated for each test. Demographics,
      vital signs, and injury severity were recorded. RESULTS: We studied 1974 major
      trauma activations. The median injury severity score was 17 [interquartile range
      9-26]; 25% were in shock; 28% were transfused; and 6% died within 24 hours.
      Overall, r-TEG correlated with CCTs. When controlling for age, injury mechanism,
      weighted-Revised Trauma Score, base excess and hemoglobin, ACT-predicted red
      blood cell (RBC) transfusion, and the alpha-angle predicted massive RBC
      transfusion better than PT/aPTT or INR (P < 0.001). The alpha-angle was superior
      to fibrinogen for predicting plasma transfusion (P < 0.001); MA was superior to
      platelet count for predicting platelet transfusion (P < 0.001); and LY-30 (rate
      of amplitude reduction 30 minutes after the MA is reached) documented
      fibrinolysis. These correlations improved for transfused, shocked or head injured
      patients. The charge for r-TEG ($317) was similar to the 5 CCTs ($286).
      CONCLUSIONS: The r-TEG data was clinically superior to results from 5 CCTs. In
      addition, r-TEG identified patients with an increased risk of early RBC, plasma
      and platelet transfusions, and fibrinolysis. Admission CCTs can be replaced with
      r-TEG.

PMID- 22868372
TI  - Plasma miR-21: a potential diagnostic marker of colorectal cancer.
AB  - OBJECTIVES: The main objective of this study was to investigate the potential use
      of circulating microRNAs (miRNAs) as biomarkers of sporadic colorectal cancer
      (CRC). BACKGROUND: CRC, a leading cause of death, is curable if detected early.
      There is an unmet need for an accurate, noninvasive biomarker of CRC. MiRNAs are
      non-protein-coding RNAs regulating gene expression that play a role in CRC
      development. METHODS: Levels of 380 miRNAs were determined using microfluidic
      array technology (Applied Biosystems) in a "training" set of 30 CRC patients from
      whom cancer and adjacent normal tissue were collected. The 4 most dysregulated
      miRNAs (P < 0.05, false discovery rate (FDR): 10%) were then validated in a
      second blinded "test" set of 16 CRC patients from whom cancer and normal adjacent
      tissue had been collected. Validated tissue miRNAs were then evaluated in a
      plasma "test" set consisting of 30 CRC patients and 30 individuals without CRC.
      The most dysregulated tissue miRNAs were then validated in an independent new
      plasma test set consisting of 20 CRC patients with 20 age-, -, and race-matched
      subjects without CRC. RESULTS: Nineteen of 380 miRNAs were dysregulated in CRC
      tissue in the tissue "training" set (P < 0.05, FDR: 10%). The 2 most upregulated
      (miR-31; miR-135b) and most downregulated (miR-1; miR-133a) miRNAs identified CRC
      in our "test" set with 100% sensitivity and 80% specificity. MiR-31 was more
      upregulated in stages III and IV compared with stages I and II (P < 0.05). In the
      "plasma" group, miR-21 differentiated CRC patients from controls with 90%
      specificity and sensitivity. CONCLUSIONS: Plasma miRNAs provide reliable and
      noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It
      seems uniquely promising as a plasma biomarker for CRC.

PMID- 22868373
TI  - Factors influencing readmission after pancreaticoduodenectomy: a multi
      institutional study of 1302 patients.
AB  - OBJECTIVE AND BACKGROUND: Morbidity, mortality, and length of hospital stay after
      pancreaticoduodenectomy (PD) have significantly decreased over recent decades.
      Despite this progress, early readmission rates after PD have been reported as
      high as 50%. Few reports have delineated factors associated with readmission
      after PD. METHODS: The medical records of 6 high-volume institutions were
      reviewed for patients who underwent PD between 2005 and 2010. Data collection
      included patient characteristics, medical comorbidities, and perioperative
      factors. Analysis included readmissions up to 90 days after PD. RESULTS: A total
      of 1302 patients underwent PD across all institutions. The 30-day and 90-day
      readmission rates were 15% and 19%, respectively. The most common reasons for 30
      day readmission included infectious complications (n = 65) and delayed gastric
      emptying (n = 29). The most common reasons for readmission after 90 days included
      wound infections and intra-abdominal abscess (n = 75) and failure to thrive (n =
      38). On multivariate analysis, factors associated with higher readmission rates
      included a preoperative diagnosis of chronic pancreatitis, higher transfusion
      requirements, and postoperative complications including intra-abdominal abscess
      and pancreatic fistula (all P < 0.02). Factors not associated with higher
      readmission rates included advanced age, body mass index,
      cardiovascular/pulmonary comorbidities, diabetes, steroid use, Whipple type
      (standard vs pylorus preserving PD), preoperative endobiliary stenting, and
      vascular reconstruction. CONCLUSIONS: These multi-institutional data represent a
      large experience of PD without the biases typically of single center studies.
      Factors related to infection, nutritional status, and delayed gastric emptying
      were the most common reasons for readmission after PD. Postoperative
      complications including pancreatic fistula predicted higher rates of readmission.

PMID- 22868374
TI  - Right portal vein ligation combined with in situ splitting induces rapid left
      lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection
      in small-for-size settings.

PMID- 22868375
TI  - Associating liver partition and portal vein ligation for staged hepatectomy: 
      will the morbidity of an additional surgery be outweighed by better patient
      outcomes in the long-term?

PMID- 22868376
TI  - Physiological, anthropometric, and performance characteristics of rugby sevens
      players.
AB  - Although the characteristics of 15-a-side rugby union players have been well
      defined, there is little information on rugby sevens players. PURPOSE: The
      authors profiled the anthropometric, physiological, and performance qualities of
      elite-level rugby sevens players and quantified relationships between these
      characteristics. METHODS: Eighteen male international rugby sevens players
      undertook anthropometric (body mass, height, sum of 7 skinfolds, lean-mass
      index), acceleration and speed (40-m sprint), muscle-power (vertical jump),
      repeated-sprint-ability (6 * 30-m sprint), and endurance (Yo-Yo Intermittent
      Recovery test and treadmill VO2max) testing. Associations between measurements
      were assessed by correlation analysis. RESULTS: Rugby sevens players had
      anthropometric characteristics (body mass 89.7 +/- 7.6 kg, height 1.83 +/- 0.06
      m, sum of 7 skinfolds 52.2 +/- 11.5 mm; mean +/- SD) similar to those of backs in
      international 15-player rugby union. Acceleration and speed (40-m sprint 5.11 +/-
      0.15 s), muscle-power (vertical jump 66 +/- 7 cm), and endurance (VO2max 53.8 +/-
      3.4 mL . kg-1 . min-1) qualities were similar to, or better than, those of
      professional 15-a-side players. Coefficients of variation ranged from 2.5% to
      22%. Relative VO2max was largely correlated with Yo-Yo distance (r = .60, .21
      .82; 90% confidence interval) and moderately correlated with 40-m sprint time (r
      = -.46, -.75 to -.02) and repeated-sprint ability (r = -.38, -.72 to .09).
      CONCLUSIONS: International rugby sevens players require highly developed speed,
      power, and endurance to tolerate the demands of competition. The small between
      athletes variability of characteristics in rugby sevens players highlights the
      need for relatively uniform physical and performance standards in contrast with
      15-a-side players.

PMID- 22868378
TI  - Effect of lithium chloride on spectral, optical, thermal and mechanical behaviour
      of bis thiourea zinc acetate crystals.
AB  - Single crystals of pure bis thiourea zinc acetate (BTZA) and lithium chloride
      (LiCl) doped BTZA have been synthesized and grown successfully from aqueous
      solutions by slow evaporation technique. The single crystals thus grown were
      characterized by different techniques such as single crystal XRD, AAS, FT-IR, UV
      Vis, TG/DTA and SHG test. The single crystal XRD study proved that the dopant has
      not changed the structure of the parent crystal. The AAS study confirmed the
      presence of lithium in the doped crystal. The FTIR study ascertained the metal
      coordination of lithium chloride doped BTZA through thiourea. The optical
      behavior of the doped crystal has been examined by UV spectral analysis. Thermal
      studies TGA & DTA of the doped crystal have been investigated and found that the
      doped crystal is thermally more stable than the pure crystal. The SHG test using
      Nd: YAG Laser confirmed the NLO activity of the pure and doped crystal. The
      obtained results are presented and discussed.

PMID- 22868379
TI  - Translating research into prosthetic and orthotic practice.
AB  - BACKGROUND: Evidence-based practice is commonly accepted as a means of improving
      patient outcomes; however, there is little understanding of the processes
      required to successfully implement it into prosthetic and orthotic practice.
      OBJECTIVES: To discuss factors affecting adoption of evidence-based practice and
      present a theoretical framework for its implementation into prosthetic and
      orthotic practice. DISCUSSION: Numerous factors that affect adoption of evidence
      based practice are discussed, ranging from individual factors to those that can
      be attributed to administrative and environmental issues. Specific factors are
      likely to be context specific and are influenced by the manner in which evidence
      based practice is introduced into the working environment. It is argued that
      successful implementation of evidence-based practice requires consideration of
      numerous interrelated factors. A formal translating research into practice model
      is presented as a means of developing a strategic plan that considers all
      relevant factors and maximizes acceptance of evidence-based practice into
      prosthetics and orthotics clinical practice. CONCLUSIONS: The use of a
      theoretical model for implementation of evidence-based practice is likely to
      improve its adoption by prosthetic and orthotic clinicians. Clinical relevance
      The demand for prosthetists/orthotists to utilize evidence-based practice is
      increasing. Lack of strategic planning throughout the implementation phase is
      likely to compromise adoption of evidence-based practices by clinicians.

PMID- 22868380
TI  - Properties of wastepaper sludge in geopolymer mortars for masonry applications.
AB  - This paper presents the results of an investigation into the use of wastepaper
      sludge in geopolymer mortar systems for manufacturing construction products. The
      investigation was driven by the increasing demand for reuse options in paper
      recycling industry. Both fresh and hardened geopolymer mortar properties are
      evaluated for samples incorporating dry wastepaper sludge, and the results
      indicate potential end-use benefits in building product manufacture. Addition of
      wastepaper sludge to geopolymer mortar reduces flow properties, primarily due to
      dry sludge absorbing water from the binder mix. The average 91-day compressive
      strength of mortar samples incorporating 2.5 wt% and 10 wt% wastepaper sludge
      respectively retained 92% and 52% of the reference mortar strength. However,
      contrary to the normal trend of increasing drying shrinkage with increasing paper
      sludge addition to Portland cement matrices, the corresponding geopolymer drying
      shrinkage decreased by 34% and 64%. Equally important, the water absorption of
      hardened geopolymer mortar decreased with increasing paper sludge content at
      ambient temperatures, providing good prospects of overall potential for
      wastepaper sludge incorporation in the production of building and masonry
      elements. The results indicate that, despite its high moisture absorbance due to
      the organic matter and residual cellulose fibre content, wastepaper sludge
      appears compatible with geopolymer chemistry, and hence serves as a potential
      supplementary additive to geopolymer cementitious masonry products.

PMID- 22868377
TI  - Innate immune responses in hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis and
      hepatocellular carcinoma worldwide and thus poses a significant public health
      threat. A hallmark of HCV infection is the extraordinary ability of the virus to
      persist in a majority of infected people. Innate immune responses represent the
      front line of defense of the human body against HCV immediately after infection.
      They also play a crucial role in orchestrating subsequent HCV-specific adaptive
      immunity that is pivotal for viral clearance. Accumulating evidence suggests that
      the host has evolved multifaceted innate immune mechanisms to sense HCV infection
      and elicit defense responses, while HCV has developed elaborate strategies to
      circumvent many of these. Defining the interplay of HCV with host innate immunity
      reveals mechanistic insights into hepatitis C pathogenesis and informs approaches
      to therapy. In this review, we summarize recent advances in understanding innate
      immune responses to HCV infection, focusing on induction and effector mechanisms
      of the interferon antiviral response as well as the evasion strategies of HCV.

PMID- 22868381
TI  - Cost-effectiveness analysis of policy instruments for greenhouse gas emission
      mitigation in the agricultural sector.
AB  - Market-based policy instruments to reduce greenhouse gas (GHG) emissions are
      generally considered more appropriate than command and control tools. However,
      the omission of transaction costs from policy evaluations and decision-making
      processes may result in inefficiency in public resource allocation and sub
      optimal policy choices and outcomes. This paper aims to assess the relative cost
      effectiveness of market-based GHG mitigation policy instruments in the
      agricultural sector by incorporating transaction costs. Assuming that farmers'
      responses to mitigation policies are economically rationale, an individual-based
      model is developed to study the relative performances of an emission tax, a
      nitrogen fertilizer tax, and a carbon trading scheme using farm data from the
      Scottish farm account survey (FAS) and emissions and transaction cost data from
      literature metadata survey. Model simulations show that none of the three schemes
      could be considered the most cost effective in all circumstances. The cost
      effectiveness depends both on the tax rate and the amount of free permits
      allocated to farmers. However, the emissions trading scheme appears to outperform
      both other policies in realistic scenarios.

PMID- 22868382
TI  - Pd-catalyzed C-3 functionalization of indolizines via C-H bond cleavage.
AB  - New transition metal-catalyzed methods for the arylation of indolizines by the
      direct cleavage of C-H bonds have been developed. A wide range of
      aryltrifluoroborate salts react with indolizines in the presence of Pd(OAc)(2)
      catalyst and AgOAc oxidant to give the arylated indolizines in high yields. Both
      electron-donating and electron-withdrawing groups perform smoothly while bromide
      and chlorine substituents are tolerated. In addition, the indolizines display
      similar reactivities in the Pd-catalyzed reaction with 3-phenylpropiolic acid to
      afford the corresponding C-3 alkynylated indolizines. These methods allow the
      direct functionalization of indolizines in one step.

PMID- 22868385
TI  - Dynamic character of charge transport parameters in disordered organic
      semiconductor field-effect transistors.
AB  - In this perspective article, we discuss the dynamic instability of charge carrier
      transport in a range of popular organic semiconductors. We observe that in many
      cases field-effect mobility, an important parameter used to characterize the
      performance of organic field-effect transistors (OFETs), strongly depends on the
      rate of the gate voltage sweep during the measurement. Some molecular systems are
      so dynamic that their nominal mobility can vary by more than one order of
      magnitude, depending on how fast the measurements are performed, making an
      assignment of a single mobility value to devices meaningless. It appears that
      dispersive transport in OFETs based on disordered semiconductors, those with a
      high density of localized trap states distributed over a wide energy range, is
      responsible for the gate voltage sweep rate dependence of nominal mobility. We
      compare such rate dependence in different materials and across different device
      architectures, including pristine and trap-dominated single-crystal OFETs, as
      well as solution-processed polycrystalline thin-film OFETs. The paramount
      significance given to a single mobility value in the organic electronics
      community and the practical importance of OFETs for applications thus suggest
      that such an issue, previously either overlooked or ignored, is in fact a very
      important point to consider when engaging in fundamental studies of charge
      carrier mobility in organic semiconductors or designing applied circuits with
      organic semiconductors.

PMID- 22868384
TI  - Vitreous levels of proteins implicated in angiogenesis are modulated in patients
      with retinal or choroidal neovascularization.
AB  - AIM: The aim of this study was to investigate the levels of pigment epithelium
      derived factor (PEDF), angiopoietin 2, vascular endothelial growth factor (VEGF),
      and soluble VEGF receptor 1 (sVEGFR-1) in vitreous samples of patients suffering
      from age-related macular degeneration with choroidal neovascularization or from
      proliferative diabetic retinopathy (PDR). METHODS: Proteins in vitreous samples
      of 29 patients were quantified via enzyme-linked immunosorbent assays. RESULTS:
      Vitreous levels of sVEGFR-1 were significantly higher in age-related macular
      degeneration with choroidal neovascularization (p = 0.005) and in PDR (p = 0.003)
      versus controls. In analogue comparisons, PEDF was significantly decreased (p <
      0.01). PDR was associated with significantly increased angiopoietin 2 and VEGF
      levels (p = 0.001 for both). CONCLUSION: The vitreous in retinal or choroidal
      neovascularization revealed a pro-angiogenic potential indicated by decreased
      PEDF or increased angiopoietin 2 levels compared to controls. However, higher
      amounts of sVEGFR-1 were concomitant, pointing to activation of an endogenous
      anti-angiogenic system in the protein network.

PMID- 22868386
TI  - Barrett's to oesophageal cancer sequence: a model of inflammatory-driven upper
      gastrointestinal cancer.
AB  - Cancer-related inflammation is considered the 'seventh hallmark of cancer'; many
      studies show that tumours develop and progress within inflammatory diseases. This
      review focuses on Barrett's oesophagus, a common condition in which chronic
      inflammation and resulting alterations in the stroma can lead to carcinogenesis,
      specifically oesophageal adenocarcinoma. Changes that occur in the tissue
      microenvironment during development of this disease are discussed. Infiltration
      of immune cells facilitates tumour development through production of factors that
      promote carcinogenesis and by enabling tumours to evade the host immune response.
      Small molecules including cytokines, chemokines and growth factors play key roles
      in both inflammation and cancer by promoting proliferation, angiogenesis and
      carcinogenesis and by recruiting immune cells. The extracellular matrix is
      altered in inflammation, and provides structural support to developing tumours.
      Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage
      and induces tumourigenic factors. Finally, tissue vasculature is a vital part of
      its microenvironment, supplying oxygen, nutrients and growth factors to rapidly
      dividing cells, and providing a mechanism for metastatic spread. The cells and
      molecules outlined here represent potential targets for treatment of this cancer,
      especially in its pre-cancerous, inflammatory stage.

PMID- 22868387
TI  - Hepatocyte growth factor and cardiomyopathy in dialysis patients.

PMID- 22868388
TI  - Short-term increase in particulate matter blunts nocturnal blood pressure dipping
      and daytime urinary sodium excretion.
AB  - Short-term exposure to ambient particulate matter with aerodynamic diameters<10
      um were found to be positively associated with blood pressure. Yet, little
      information exists regarding the association between particles and circadian
      rhythm of blood pressure. Hence, we analyzed the association of exposure to
      particulate matter with aerodynamic diameters<10 um on the day of examination and
      <=7 days before with ambulatory blood pressure and with sodium excretion in 359
      adults from the general population using multiple linear regression. After
      controlling for potential confounders, a 10-ug/m3 increase in particulate matter
      with aerodynamic diameters<10 um levels was associated with nighttime systolic
      blood pressure (beta=1.32 mm Hg 95% CI, 0.06-2.58 mm Hg at lag 0; P=0.04),
      nighttime diastolic blood pressure (0.72 mm Hg 95% CI, 0.03-1.42 mm Hg at lag 2;
      P=0.04), nocturnal systolic blood pressure dipping (-0.96 mm Hg 95% CI, -1.89 to 
      0.03 mm Hg at lag 0; P=0.044), and daytime urinary sodium excretion (-0.05 log
      mmol/min 95% CI, -0.10 to -0.01 log-mmol/min at lag 0; P=0.027) but not with
      nighttime sodium excretion. The associations with blood pressure rapidly
      diminished with increasing lag days, and the associations with daytime sodium
      excretion were maximal with particulate matter with aerodynamic diameters<10 um
      in exposures 2 to 5 days before. The associations of short-term increases in
      particulate matter with aerodynamic diameters<10 um with higher nighttime blood
      pressure and blunted systolic blood pressure dipping were preceded by
      associations with reduced ability of the kidney to excrete sodium during daytime.
      The underlying mechanism linking air pollution to increased cardiovascular risk
      may include disturbed circadian rhythms of renal sodium handling and blood
      pressure.

PMID- 22868389
TI  - Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in
      hypertension through a glucagon-like peptide 1-dependent mechanism.
AB  - Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor, inhibits the
      inactivation and degradation of glucagon like peptide 1 (GLP-1), which is used
      for the treatment of type 2 diabetes mellitus. However, little is known about the
      role of GLP-1 in hypertension. This study investigated whether the activation of
      GLP-1 signaling protects endothelial function in hypertension. Two-week
      sitagliptin treatment (10 mg/kg per day, oral gavage) improved endothelium
      dependent relaxation in renal arteries, restored renal blood flow, and reduced
      systolic blood pressure in spontaneously hypertensive rats. In vivo sitagliptin
      treatment elevated GLP-1 and GLP-1 receptor expressions, increased cAMP level,
      and subsequently activated protein kinase A, liver kinase B1, AMP-activated
      protein kinase-alpha and endothelial NO synthase in spontaneously hypertensive
      rat renal arteries. Inhibition of GLP-1 receptor, adenylyl cyclase, protein
      kinase A, AMP-activated protein kinase-alpha, or NO synthase reversed the
      protective effects of sitagliptin. We also demonstrate that GLP-1 receptor
      agonist exendin 4 in vitro treatment had similar vasoprotective effects in
      spontaneously hypertensive rat renal arteries and increased NO production in
      spontaneously hypertensive rat aortic endothelial cells. Studies using transient
      expressions of wild-type and dominant-negative AMP-activated protein kinase
      alpha2 support the critical role of AMP-activated protein kinase-alpha in
      mediating the effect of GLP-1 in endothelial cells. Ex vivo exendin 4 treatment
      also improved endothelial function of renal arteries from hypertensive patients.
      Our results elucidate that upregulation of GLP-1 and related agents improve
      endothelial function in hypertension by restoring NO bioavailability, suggesting
      that GLP-1 signaling could be a therapeutic target in hypertension-related
      vascular events.

PMID- 22868390
TI  - Vascular aspects of Fabry disease in relation to clinical manifestations and
      elevations in plasma globotriaosylsphingosine.
AB  - Fabry disease is an X-linked hereditary lysosomal storage disorder attributed to
      a deficiency of alpha-galactosidase A leading to increased plasma levels of
      globotriaosylsphingosine (lysoGb3). The disease presents as a vascular disease,
      with cerebral, cardiac, and renal complications. Carotid intima-media thickness
      (IMT), brachial flow-mediated dilation (FMD), pulse wave velocity, and advanced
      glycation end products were measured in 57 classically affected patients (22 men
      and 35 women), 55 healthy matched controls (20 men and 35 women), and 10 atypical
      Fabry disease patients (5 men and 5 women). Most patients received enzyme
      replacement therapy. In classically affected male patients, brachial FMD was
      decreased (2.9% [95% CI, 0.8% to 7.9%] versus 5.9% [2.1% to 8.5%] in controls;
      P=0.01), and carotid IMT was increased (0.67 mm [95% CI, 0.50-0.96 mm] versus
      0.59 mm [95% CI, 0.40-0.76 mm] in controls; P=0.01). In women and atypical
      patients these vascular parameters were comparable with controls. Pulse wave
      velocity was not different; advanced glycation end products were only slightly
      increased in atypical patients. In classically affected women, a small increase
      in lysoGb3 was associated with an increase in IMT independent of age. In the
      classically affected men, all with increased IMT and high levels of plasma
      lysoGb3, lysoGb3 levels did not add to a higher IMT, suggestive of a ceiling
      effect. For FMD, elevated lysoGb3 levels (>7 nmol/L) contributed to a 2.9% lower
      FMD independent of age and sex (P=0.02). Increased carotid IMT and decreased
      brachial FMD occur in classic Fabry disease, which is associated with plasma
      lysoGb3 level independent of age and sex. These observations still exist despite
      enzyme replacement therapy.

PMID- 22868391
TI  - Implications of new hypertension guidelines in the United States.
AB  - The American Heart Association released a scientific statement based on available
      clinical trials and expert opinion in 2007 for the treatment of hypertension to
      prevent coronary artery disease. These guidelines recommend more aggressive
      control of blood pressure (BP <130/80 mm Hg) among those at high risk for
      coronary artery disease, individuals with diabetes mellitus, chronic kidney
      disease, coronary artery disease or coronary artery disease risk equivalent, or a
      10-year Framingham risk score >=10%. Based on newer clinical trial data, the 2011
      American College of Cardiology Foundation/American Heart Association (AHA)
      hypertension guidelines for the elderly recommend a less aggressive approach of
      <145/90 mm Hg in those over the age of 80 years. We estimated the burden of
      uncontrolled BP among those at an increased risk of coronary artery disease using
      the both the 2007 AHA and the 2011 American College of Cardiology Foundation/AHA
      hypertension guidelines. We used a cross-sectional analysis of National Health
      and Nutrition Examination Survey 2005-2008 participants. Participants were 10198
      adults aged 18 to 85 years. Using the 2011 American College of Cardiology
      Foundation/AHA hypertension guidelines (>=140/90 mm Hg), 72 million Americans
      (35%) have hypertension. Using the 2007 AHA guidelines, an additional 7 million
      American adults (5%) have elevated BP requiring treatment, for a total of 79
      million adults (40%). Although individuals at a higher risk for coronary artery
      disease are more likely to be aware of their hypertension and to be taking
      antihypertension medication, they are less likely to have their BP under control.
      Additional efforts are needed in the treatment of elevated BP, especially among
      individuals with an increased risk of coronary artery disease.

PMID- 22868392
TI  - Death-associated protein kinase 3 mediates vascular inflammation and development
      of hypertension in spontaneously hypertensive rats.
AB  - Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated
      serine/threonine kinase that mediates cell death. Our recent study demonstrated
      that DAPK3 protein increases in the mesenteric artery from spontaneously
      hypertensive rats compared with Wistar Kyoto rats. Pathogenesis of hypertension
      is modulated at least in part by vascular inflammation. We examined whether DAPK3
      mediates vascular inflammatory responses and development of hypertension. In rat
      mesenteric arterial smooth muscle cells, small interfering RNA against DAPK3
      inhibited vascular cell adhesion molecule 1 expression and monocyte adhesion
      induced by tumor necrosis factor-alpha. DAPK3 small interfering RNA inhibited
      phosphorylation of c-Jun amino-terminal kinase, p38, and Akt, as well as reactive
      oxygen species (ROS) production induced by tumor necrosis factor-alpha. In human
      umbilical vein endothelial cells, expressions of vascular cell adhesion molecule
      1, endothelial selectin, and cyclooxygenase 2, as well as ROS production induced
      by tumor necrosis factor-alpha, were inhibited by DAPK inhibitor. In vivo, blood
      pressure, ROS production, inflammatory molecule expression (vascular cell
      adhesion molecule 1 and endothelial selectin), and hypertrophy in isolated
      mesenteric artery were elevated in spontaneously hypertensive rats (10 weeks
      old), which were prevented by long-term treatment with a DAPK inhibitor (500
      ug/kg per day for 6 weeks). In isolated mesenteric artery, the increased
      angiotensin II-induced contraction and the impaired acetylcholine-induced
      endothelium-dependent relaxation in spontaneously hypertensive rats were reversed
      by a DAPK inhibitor. The present results for the first time demonstrated in
      cultured smooth muscle cells and endothelial cells that DAPK3 mediates tumor
      necrosis factor-induced inflammatory responses via ROS-dependent mechanisms. It
      is also suggested that DAPK3 mediates the development of hypertension in
      spontaneously hypertensive rats likely via ROS-dependent inflammation,
      hypertrophy, and hypercontractility.

PMID- 22868393
TI  - Autoantibody-mediated complement C3a receptor activation contributes to the
      pathogenesis of preeclampsia.
AB  - Preeclampsia (PE) is a prevalent life-threatening hypertensive disorder of
      pregnancy associated with increased complement activation. However, the causative
      factors and pathogenic role of increased complement activation in PE are largely
      unidentified. Here we report that a circulating maternal autoantibody, the
      angiotensin II type 1 receptor agonistic autoantibody, which emerged recently as
      a potential pathogenic contributor to PE, stimulates deposition of complement C3
      in placentas and kidneys of pregnant mice via angiotensin II type 1 receptor
      activation. Next, we provide in vivo evidence that selectively interfering with
      C3a signaling by a complement C3a receptor-specific antagonist significantly
      reduces hypertension from 167+/-7 to 143+/-5 mm Hg and proteinuria from 223.5+/
      7.5 to 78.8+/-14.0 MUg of albumin per milligram creatinine (both P<0.05) in
      angiotensin II type 1 receptor agonistic autoantibody-injected pregnant mice. In
      addition, we demonstrated that complement C3a receptor antagonist significantly
      inhibited autoantibody-induced circulating soluble fms-like tyrosine kinase 1, a
      known antiangiogenic protein associated with PE, and reduced small placental size
      with impaired angiogenesis and intrauterine growth restriction. Similarly, in
      humans, we demonstrate that C3 deposition is significantly elevated in the
      placentas of preeclamptic patients compared with normotensive controls. Lastly,
      we show that complement C3a receptor activation is a key mechanism underlying
      autoantibody-induced soluble fms-like tyrosine kinase 1 secretion and decreased
      angiogenesis in cultured human villous explants. Overall, we provide mouse and
      human evidence that angiotensin II type 1 receptor agonistic autoantibody
      mediated activation contributes to elevated C3 and that complement C3a receptor
      signaling is a key mechanism underlying the pathogenesis of the disease. These
      studies are the first to link angiotensin II type 1 receptor agonistic
      autoantibody with complement activation and to provide important new
      opportunities for therapeutic intervention in PE.

PMID- 22868394
TI  - Identification of hypertension susceptibility loci on rat chromosome 12.
AB  - Previous studies have identified multiple blood pressure and renal disease
      quantitative trait loci located on rat chromosome 12. In the present study, we
      narrowed blood pressure loci using a series of overlapping Dahl salt
      sensitive/Mcwi (SS)-12 Brown Norway (BN) congenic lines. We found that
      transferring 6.1 Mb of SS chromosome 12 (13.4-19.5 Mb) onto the consomic SS-12BN
      background significantly elevated blood pressure on 1% NaCl (146+/-6 versus 127+/
      1 mm Hg; P<0.001) and 8% NaCl diets (178+/-7 versus 144+/-2 mm Hg; P<0.001).
      Compared with the SS-12BN consomic, these animals also had significantly elevated
      albumin (218+/-31 versus 104+/-8 mg/d; P<0.001) and protein excretion (347+/-41
      versus 195+/-12 mg/d; P<0.001) on a 1% NaCl diet. Elevated blood pressure,
      albuminuria, and proteinuria coincided with greater renal and cardiac damage,
      demonstrating that SS allele(s) within the 6.1 Mb congenic interval are
      associated with strong cardiovascular disease phenotypes. Sequence analysis of
      the 6.1 Mb congenic region revealed 12 673 single nucleotide polymorphisms
      between SS and BN rats. Of these polymorphisms, 293 lie within coding regions,
      and 18 resulted in nonsynonymous changes in conserved genes, of which 5 were
      predicted to be potentially damaging to protein function. Syntenic regions in
      human chromosome 7 have also been identified in multiple linkage and association
      studies of cardiovascular disease, suggesting that genetic variants underlying
      cardiovascular phenotypes in this congenic strain can likely be translated to a
      better understanding of human hypertension.

PMID- 22868395
TI  - Mercury exposure and risk of hypertension in US men and women in 2 prospective
      cohorts.
AB  - Cross-sectional studies and animal experiments suggest that methylmercury
      exposure could increase the risk of hypertension. This relationship has not been
      evaluated in large prospective studies. Using data from previous nested case
      control studies in 2 separate prospective cohorts, we measured toenail mercury, a
      valid biomarker of long-term methylmercury exposure, among 6045 US men and women
      free of hypertension at baseline. Geometric mean toenail mercury concentrations
      were 0.08 MUg/g in the lowest quintile and 0.74 MUg/g in the highest quintile,
      the latter corresponding with exposures ~2.0-fold higher than the US
      Environmental Protection Agency reference dose. Participants were followed
      prospectively (mean+/-SD follow-up, 14.9+/-7.9 years) for a new self-report of
      physician-diagnosed hypertension (3540 cases), shown to be >95% sensitive and
      specific for diagnosing hypertension in these cohorts as compared with review of
      medical charts and direct blood pressure measurement, respectively. After
      adjustment for demographic, clinical, and lifestyle risk factors, the hazard
      ratio (95% CI) for incident hypertension in the highest versus lowest quintile of
      mercury exposure was 0.96 (0.84-1.09) in women, 0.82 (0.62-1.08) in men, and 0.94
      (0.84-1.06) in both cohorts combined. Findings were similar when more extreme
      categories of mercury were compared (across deciles, with geometric mean levels
      in highest decile ~2.9-fold higher than the reference dose) and in analyses
      stratified by fish or omega-3 consumption, selenium levels, body mass index, and
      age. These findings from 2 separate large prospective cohort studies do not
      support any clinically apparent adverse effects of methylmercury exposure on the
      risk of hypertension in men or women, including at levels <=2.5-fold higher than
      the reference dose.

PMID- 22868396
TI  - Lifestyle factors and antihypertensive treatment on the risks of ischemic and
      hemorrhagic stroke.
AB  - The joint relationship between healthy lifestyle and antihypertensive treatment
      with stroke risk is unclear. We prospectively investigated the individual and
      joint effects of healthy lifestyle factors and antihypertensive treatment on
      stroke risk among 36,686 Finnish participants aged 25 to 74 years and free of
      coronary heart disease and stroke at baseline. During a mean follow-up of 13.7
      years, 1478 people developed stroke event (1167 ischemic and 311 hemorrhagic).
      The stroke risk was significantly decreased in people who adhered to >=3 healthy
      lifestyle factors (never smoking, normal weight, moderate/high level of exercise,
      vegetable consumption>=3 times per week, and light/moderate alcohol drinking)
      compared with those who adhered to <3 healthy lifestyle factors. The stroke risk
      was significantly increased in unaware untreated, aware untreated, aware treated
      and controlled, and aware treated and uncontrolled hypertensive people than in
      normotensive people. The risks of stroke were decreased in people who adhered to
      >=3 healthy lifestyle factors compared with those who adhered to <3 healthy
      lifestyle factors within different hypertensive status. Compared with
      hypertensive people who did not use antihypertensive drugs and adhered to >=3
      healthy lifestyle factors, the multivariable-adjusted hazard ratios in
      hypertensive people who used antihypertensive drugs and adhered to <3 healthy
      lifestyle factors were associated with 37% to 42% increased risks of total,
      ischemic, and hemorrhagic stroke in men and 121% to 131% increased risks of
      stroke in women. The present study demonstrates that a healthy lifestyle
      significantly decreases stroke risk in both men and women in different strata of
      hypertension status and antihypertensive drug treatments.

PMID- 22868397
TI  - Retraction. Implications of new hypertension guidelines in the United States.

PMID- 22868398
TI  - The effect of hypercholesterolemia on carbachol-induced contractions of the
      detrusor smooth muscle in rats: increased role of L-type Ca2+ channels.
AB  - To investigate a possible relation between hypercholesterolemia and detrusor
      smooth muscle function, we studied the contractile response to potassium
      challenge, carbachol (CCh), and the components of CCh-induced contractile
      mechanism in high-cholesterol diet-fed rats. Adult male Sprague-Dawley rats were
      fed with standard (control group, N = 17) or 4 % cholesterol diet
      (hypercholesterolemia group (HC), N = 16) for 4 weeks. Spontaneous contractions
      of detrusor muscle strips and their responses to potassium chloride (KCl) or
      cumulative dose-contraction curves to CCh were recorded. The effects of
      muscarinic receptor antagonists (methoctramin and/or 4-diphenylacetoxy-N
      methylpiperidine), L-type Ca(+2) channel blocker (nifedipine), and/or rho-kinase
      inhibitor Y-27632 were investigated. Blood cholesterol level was increased in the
      HC group with no sign of atherosclerosis. The KCl-induced detrusor smooth muscle
      contractions were higher in HC, whereas spontaneous and CCh-induced responses
      were similar in both groups. Preincubation with receptor antagonist for M(3) but
      not for M(2) attenuated contraction significantly, shifting the dose-response
      curve to the right. This response was similar in both groups. Among two effector
      mechanisms of M(3)-mediated detrusor smooth muscle contraction, rho-kinase
      pathway was not affected by hypercholesterolemia, whereas blockade of L-type
      Ca(+2) channels potently reduced contractions. The results of this study point
      out a relation between hypercholesterolemia and contractile mechanism of detrusor
      smooth muscle likely to change urinary bladder function, via altering L-type
      Ca(+2) channels. Taken together with escalating incidence of hypercholesterolemia
      and lower urinary tract symptoms, it is a field which deserves to be investigated
      further.

PMID- 22868400
TI  - Effective dose conversion coefficients for radionuclides exponentially
      distributed in the ground.
AB  - In order to provide fundamental data required for dose evaluation due to
      environmental exposures, effective dose conversion coefficients, that is, the
      effective dose rate per unit activity per unit area, were calculated for a number
      of potentially important radionuclides, assuming an exponential distribution in
      ground, over a wide range of relaxation depths. The conversion coefficients were
      calculated for adults and a new-born baby on the basis of dosimetric methods that
      the authors and related researchers have previously developed, using Monte Carlo
      simulations and anthropomorphic computational phantoms. The differences in
      effective dose conversion coefficients due to body size between the adult and
      baby phantoms were found to lie within 50 %, for most cases; however, for some
      low energies, differences could amount to a factor of 3. The effective dose per
      unit source intensity per area was found to decrease by a factor of 2-5, for
      increasing relaxation depths from 0 to 5 g/cm(2), above a source energy of 50
      keV. It is also shown that implementation of the calculated coefficients into the
      computation of the tissue weighting factors and the adult reference computational
      phantoms of ICRP Publication 103 does not significantly influence the effective
      dose conversion coefficients of the environment. Consequently, the coefficients
      shown in this paper could be applied for the evaluation of effective doses, as
      defined according to both recommendations of ICRP Publications 103 and 60.

PMID- 22868399
TI  - Slipping and tripping: fall injuries in adults associated with rugs and carpets.
AB  - BACKGROUND: Falls are a leading cause of unintentional injury among adults age 65
      years and older. Loose, unsecured rugs and damaged carpets with curled edges, are
      recognized environmental hazards that may contribute to falls. To characterize
      nonfatal, unintentional fall-related injuries associated with rugs and carpets in
      adults aged 65 years and older. METHODS: We conducted a retrospective analysis of
      surveillance data of injuries treated in hospital emergency departments (EDs)
      during 2001-2008. We used the National Electronic Injury Surveillance System-All
      Injury Program, which collects data from a nationally representative stratified
      probability sample of 66 U.S. hospital EDs. Sample weights were used to make
      national estimates. RESULTS: Annually, an estimated 37,991 adults age 65 years or
      older were treated in U.S. EDs for falls associated with carpets (54.2%) and rugs
      (45.8%). Most falls (72.8%) occurred at home. Women represented 80.2% of fall
      injuries. The most common location for fall injuries in the home was the bathroom
      (35.7%). Frequent fall injuries occurred at the transition between carpet/rug and
      non-carpet/rug, on wet carpets or rugs, and while hurrying to the bathroom.
      CONCLUSIONS: Fall injuries associated with rugs and carpets are common and may
      cause potentially severe injuries. Older adults, their caregivers, and emergency
      and primary care physicians should be aware of the significant risk for fall
      injuries and of environmental modifications that may reduce that risk.

PMID- 22868401
TI  - Fabrication of hybrid nanostructured arrays using a PDMS/PDMS replication
      process.
AB  - In the study, a novel and low cost nanofabrication process is proposed for
      producing hybrid polydimethylsiloxane (PDMS) nanostructured arrays. The proposed
      process involves monolayer self-assembly of polystyrene (PS) spheres, PDMS
      nanoreplication, thin film coating, and PDMS to PDMS (PDMS/PDMS) replication. A
      self-assembled monolayer of PS spheres is used as the first template. Second, a
      PDMS template is achieved by replica moulding. Third, the PDMS template is coated
      with a platinum or gold layer. Finally, a PDMS nanostructured array is developed
      by casting PDMS slurry on top of the coated PDMS. The cured PDMS is peeled off
      and used as a replica surface. In this study, the influences of the coating on
      the PDMS topography, contact angle of the PDMS slurry and the peeling off ability
      are discussed in detail. From experimental evaluation, a thickness of at least 20
      nm gold layer or 40 nm platinum layer on the surface of the PDMS template
      improves the contact angle and eases peeling off. The coated PDMS surface is
      successfully used as a template to achieve the replica with a uniform array via
      PDMS/PDMS replication process. Both the PDMS template and the replica are free of
      defects and also undistorted after demoulding with a highly ordered hexagonal
      arrangement. In addition, the geometry of the nanostructured PDMS can be
      controlled by changing the thickness of the deposited layer. The simplicity and
      the controllability of the process show great promise as a robust nanoreplication
      method for functional applications.

PMID- 22868402
TI  - [Frozen sections diagnostics in visceral surgery. Stomach and intestines].
AB  - A close collaboration between clinicians and pathologists is essential for
      establishing an optimal therapeutic concept concerning disorders of the stomach
      and intestines. Intraoperative frozen sections form part of this cooperation in
      order to obtain an intraoperative diagnosis or to clarify unclear findings and to
      be able to adapt operative procedures accordingly. For avoiding mistakes,
      knowledge of indications as well as limitations of intraoperative frozen sections
      of the stomach and intestines is mandatory. The same objective is pursued by
      establishing an unhindered flow of information.

PMID- 22868403
TI  - [Rapid frozen sections in neuropathology].
AB  - Neuropathological evaluation of frozen sections requires a) special expertise in
      neuropathological specimen assessment and neurooncology as well as b) a trustful
      and open communication culture with the neurosurgeons. In addition to frozen
      sections, cytological examinations of smear and touch preparations as supporting
      methods are available to reach a correct diagnosis: these additional methods
      should therefore be performed whenever possible. Besides evaluation of biopsy
      specimens, appraisal of resection specimens and resection margin controls are of
      high clinical relevance. In the case of diffusely infiltrating central nervous
      system (CNS) neoplasms, in particular gliomas, resection margin control is often
      not feasible in contrast to other types of solid tumor.

PMID- 22868404
TI  - Improvement of 800-m running performance with prior high-intensity exercise.
AB  - Prior high-intensity exercise increases the oxidative energy contribution to
      subsequent exercise and may enhance exercise tolerance. The potential impact of a
      high-intensity warm-up on competitive performance, however, has not been
      investigated. PURPOSE: To test the hypothesis that a high-intensity warm-up would
      speed VO2 kinetics and enhance 800-m running performance in well-trained
      athletes. METHODS: Eleven highly trained middle-distance runners completed two
      800-m time trials on separate days on an indoor track, preceded by 2 different
      warm-up procedures. The 800-m time trials were preceded by a 10-min self-paced
      jog and standardized mobility drills, followed by either 6 * 50-m strides
      (control [CON]) or 2 * 50-m strides and a continuous high-intensity 200-m run
      (HWU) at race pace. Blood [La] was measured before the time trials, and VO2 was
      measured breath by breath throughout exercise. RESULTS: 800-m time-trial
      performance was significantly faster after HWU (124.5 +/- 8.3 vs CON, 125.7 +/-
      8.7 s, P < .05). Blood [La] was greater after HWU (3.6 +/- 1.9 vs CON, 1.7 +/-
      0.8 mM; P < .01). The mean response time for VO2 was not different between
      conditions (HWU, 27 +/- 6 vs CON, 28 +/- 7 s), but total O2 consumed (HWU, 119 +/
      18 vs CON, 109 +/- 28 ml/kg, P = .05) and peak VO2 attained (HWU, 4.21 +/- 0.85
      vs CON, 3.91 +/- 0.63 L/min; P = .08) tended to be greater after HWU.
      CONCLUSIONS: These data indicate that a sustained high-intensity warm-up enhances
      800-m time-trial performance in trained athletes.

PMID- 22868405
TI  - Laparoendoscopic single-site surgery for symptomatic renal cyst decortication
      using a homemade glove port device: initial experience.
AB  - OBJECTIVES: Laparoendoscopic single-site surgery (LESS) has recently gained
      popularity in urology. There are few large series reports on LESS for symptomatic
      renal cysts. We evaluated the clinical utility and safety of LESS in 62
      symptomatic renal cyst decortication patients by using a homemade glove port
      device. MATERIALS AND METHODS: We reviewed our series of 62 LESS for symptomatic
      renal cyst (20 Bosniak type I and 42 Bosniak type II) decortication performed
      from November 2009 to December 2010. A homemade glove port device was placed
      through an umbilical incision. The perioperative clinical parameters were
      reviewed retrospectively. RESULTS: Of 62 cases that underwent LESS for renal cyst
      ablation successfully, there were no major perioperative complications, but 2
      minor complications (transient fever and mild ileus) were found. The mean
      operative time was 61.4 +/- 27.4 min and the mean estimated blood loss was 20.1
      +/- 11.3 ml. The mean pre- and postoperative pain scores were 6.94 +/- 1.1 (range
      5-10) and 1.3 +/- 1.2 (0-5), respectively (p = 0.000). CONCLUSIONS: Our results
      suggest that LESS is a safe and feasible alternative to conventional laparoscopic
      surgery for the treatment of symptomatic renal cysts.

PMID- 22868406
TI  - Selective reduction of ketones using water as a hydrogen source under high
      hydrostatic pressure.
AB  - A selective reduction of a broad variety of ketones is described. The method is
      based on the combination of a Ni-Al alloy and high hydrostatic pressure (HHP, 2.8
      kbar) in an aqueous medium. The reaction of the Ni-Al alloy with water provides
      in situ hydrogen generation and the high pressure ensures that the H(2) formed
      remains in the solution, thus the C=O reduction readily occurs. The application
      of the HHP resulted in selective formation of the desired products and the common
      problem of non-selective overhydrogenation could be avoided. In most cases the
      reductions resulted in high yields and excellent selectivities without the use of
      any base.

PMID- 22868408
TI  - The impact of upper cut-off voltages on the electrochemical behaviors of
      composite electrode 0.3Li2MnO3.0.7LiMn1/3Ni1/3Co1/3O2.
AB  - This work has initiated an investigation on the electrochemical behaviors and the
      structure changes of the composite electrode
      0.3Li(2)MnO(3).0.7LiMn(1/3)Ni(1/3)Co(1/3)O(2) when charged with different cut-off
      voltages. It is found that the charge cut-off voltages could not only affect the
      capacity property and coulombic efficiency, but also alter the electrode kinetics
      of the composite. As a consequence, the electrochemical activation of the
      composite electrode is highly dependent on the charge cut-off voltages: when the
      charge cut-off voltage is higher than 4.5 V, the inert component Li(2)MnO(3) in
      the composite electrode is completely activated. At the meanwhile, there occurred
      an irreversible oxygen loss during the initial charge process, which yielded a
      hollow sphere in the electrode. Regardless of charge voltages, Mn ions in the
      composite electrode were presented in an oxidation state of +4, while Co(2+) ions
      were detected at the surface of the electrode when cycled at low voltages. Ni
      ions in the composite could react with organic or inorganic species and then
      cover the surface of the cycled electrode.

PMID- 22868407
TI  - The parasacral sciatic nerve block does not induce anesthesia of the obturator
      nerve.
AB  - PURPOSE: The ability of the parasacral sciatic nerve block (PSNB) to induce
      anesthesia of the obturator nerve remains controversial. Our objective was to
      evaluate the anesthesia of the obturator nerve after a PSNB. METHODS: Forty
      patients scheduled to undergo knee surgery (anterior cruciate ligament
      reconstruction) were included in this prospective, randomized, controlled study.
      Patients were randomized to receive PSNB alone (control group, n = 20) or PSNB in
      combination with an obturator nerve block (obturator group, n = 20). After
      evaluation for 30 min, the two groups received a femoral nerve block, and
      patients were taken to surgery. The obturator nerve blockade was assessed by
      measurement of adductor strength at baseline (T0) and every 10 min during the 30
      min evaluation (T10, T20, and T30). Pain scores after tourniquet inflation and
      during surgery were compared between the two groups. The requirement for
      additional intravenous analgesia and/or sedation was also recorded. RESULTS: The
      two groups had comparable demographic and surgical characteristics. Four patients
      were excluded from the study because of PSNB or femoral nerve block failure. The
      adductor strength values were similar between groups at T0 but were significantly
      lower in the obturator group at T10, T20, and T30 (p < 0.0001). Patients in the
      obturator group reported less pain than those in the control group (p < 0.05).
      They also required less additional intravenous sedation and/or analgesia (p <
      0.05). CONCLUSION: This clinical study demonstrated that the PSNB is an
      unreliable means of inducing anesthesia of the obturator nerve and emphasizes the
      need to block this nerve separately to induce adequate analgesia during knee
      surgery.

PMID- 22868409
TI  - What spectroscopy reveals concerning the Mn oxidation levels in the oxygen
      evolving complex of photosystem II: X-ray to near infra-red.
AB  - Photosystem II (PS II), found in oxygenic photosynthetic organisms, catalyses the
      most energetically demanding reaction in nature, the oxidation of water to
      molecular oxygen and protons. The water oxidase in PS II contains a Mn(4)Ca
      cluster (oxygen evolving complex, OEC), whose catalytic mechanism has been
      extensively investigated but is still unresolved. In particular the precise Mn
      oxidation levels through which the cluster cycles during functional turnover are
      still contentious. In this, the first of several planned parts, we examine a
      broad range of published data relating to this question, while considering the
      recent atomic resolution PS II crystal structure of Umena et al. (Nature, 2011,
      473, 55). Results from X-ray, UV-Vis and NIR spectroscopies are considered, using
      an approach that is mainly empirical, by comparison with published data from
      known model systems, but with some reliance on computational or other theoretical
      considerations. The intention is to survey the extent to which these data yield a
      consistent picture of the Mn oxidation states in functional PS II - in
      particular, to test their consistency with two current proposals for the mean
      redox levels of the OEC during turnover; the so called 'high' and 'low' oxidation
      state paradigms. These systematically differ by two oxidation equivalents
      throughout the redox accumulating catalytic S state cycle (states S(0)...S(3)).
      In summary, we find that the data, in total, substantially favor the low
      oxidation proposal, particularly as a result of the new analyses we present. The
      low oxidation state scheme is able to resolve a number of previously 'anomalous'
      results in the observed UV-Visible S state turnover spectral differences and in
      the resonant inelastic X-ray spectroscopy (RIXS) of the Mn pre-edge region of the
      S(1) and S(2) states. Further, the low oxidation paradigm is able to provide a
      'natural' explanation for the known sensitivity of the OEC Mn cluster to
      cryogenic near infra-red (NIR) induced turnover to alternative spin/redox states
      in S(2) and S(3).

PMID- 22868410
TI  - Mecamylamine elicits withdrawal-like signs in rats following a single dose of
      nicotine.
AB  - RATIONALE: The ability of nicotine to induce dependence (result in a withdrawal
      syndrome) is typically thought to require long-term, daily smoking. Emerging
      evidence suggests that symptoms of nicotine withdrawal may occur following only a
      few cigarettes. Whether acute exposure to nicotine can induce dependence in
      animals has not been well established. OBJECTIVE: The objective of this paper is
      to examine whether the nicotinic acetylcholine receptor antagonist mecamylamine
      elicits withdrawal-like signs in rats following acute nicotine exposure. METHODS
      AND RESULTS: Mecamylamine (3.0 mg/kg, s.c.) administered ~2 h after a single dose
      of nicotine (0.5 mg/kg, s.c.) elicited increases in intracranial self-stimulation
      (ICSS) thresholds and somatic signs, two well-established effects of withdrawal
      from long-term (chronic) nicotine exposure. The magnitude of these effects
      remained constant across five daily test sessions. A lower dose of mecamylamine
      (1.5 mg/kg, s.c.) had little or no effect on ICSS thresholds or somatic signs
      following acute nicotine exposure, but precipitated robust increases in these
      measures during a chronic nicotine infusion. Finally, rats exhibited a small
      increase in ICSS thresholds over time following a single nicotine injection (0.5
      mg/kg, s.c.), possibly reflecting a modest spontaneous withdrawal-like effect.
      CONCLUSIONS: Mecamylamine elicited withdrawal-like signs in rats following a
      single dose of nicotine. The different effects of mecamylamine 1.5 mg/kg
      following acute versus chronic nicotine exposure supports the notion that these
      models simulate the early and more advanced stages of nicotine dependence,
      respectively. While further optimization and validation of these models is
      necessary, they may provide a novel approach for studying the earliest stages of
      nicotine dependence.

PMID- 22868411
TI  - Evaluation of dopamine D2/D3 and serotonin 5-HT2A receptor occupancy for a novel
      antipsychotic, lurasidone, in conscious common marmosets using small-animal
      positron emission tomography.
AB  - RATIONALE: Lurasidone is a novel antipsychotic drug with potent binding affinity
      for dopamine D(2) and serotonin (5-hydroxytryptamine, 5-HT)(2A), 5-HT(7), and 5
      HT(1A) receptors. Previous pharmacological studies have revealed that lurasidone
      exhibits a preferable profile (potent antipsychotic activity and lower incidence
      of catalepsy) to other antipsychotic drugs, although the contribution of receptor
      subtypes to this profile remains unclear. OBJECTIVES: To compare target
      engagements of lurasidone with those of an atypical antipsychotic, olanzapine, we
      performed evaluation of dopamine D(2)/D(3) and serotonin 5-HT(2A) receptor
      occupancy in vivo by positron emission tomography (PET) with conscious common
      marmosets. METHODS: We measured brain receptor occupancies in conscious common
      marmosets after oral administrations of lurasidone or olanzapine by PET with
      [(11)C]raclopride and [(11)C]R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenylethyl)]-4-piperidine methanol (MDL 100907) for D(2)/D(3) and 5-HT(2A)
      receptors, respectively. RESULTS: Increases in brain D(2)/D(3) receptor
      occupancies of both lurasidone and olanzapine, which reached >80 % at maximum,
      were observed in the striatum with significant correlations to plasma drug
      levels. However, lurasidone showed lower 5-HT(2A) receptor occupancy in the
      frontal cortex within the same dose range, while olanzapine showed broadly
      comparable 5-HT(2A) and D(2)/D(3) receptor occupancies. CONCLUSIONS: Compared
      with olanzapine, lurasidone preferentially binds to D(2)/D(3) receptors rather
      than 5-HT(2A) receptors in common marmosets. These results suggest that the
      contribution of in vivo 5-HT(2A) receptor blocking activity to the
      pharmacological profile of lurasidone might differ from olanzapine in terms of
      the low risk of extrapyramidal syndrome and efficacy against negative symptoms.

PMID- 22868412
TI  - Effects of sex and rearing environment on imipramine response in mice.
AB  - RATIONALE: Antidepressant treatments are commonly prescribed, but few studies
      have been published, even in animal models, on differences in reactivity to
      antidepressants with respect to rearing environment and sex. OBJECTIVES: Using a
      mouse model, we investigated the hypothesis that rearing environment (weaning
      time) and sex could impact responses to imipramine treatment. METHODS: ICR mice
      were assigned to four groups for each sex: early weaned saline or imipramine
      treated, normally weaned saline or imipramine treated. Early weaning was
      conducted on postnatal day 14. All groups were injected intraperitoneally with
      drug or vehicle for 2 weeks from the age of 6 weeks and tested in the elevated
      plus maze to estimate anxiety levels. Hippocampal neurogenesis was also assessed
      with immunostaining for calretinin and calbindin because it has suggested that
      neurogenesis is required for the behavioral effects of antidepressants. RESULTS:
      Imipramine treatment decreased anxiety levels in females, but not in males, in
      the normal weaning condition. By contrast, the same treatment decreased anxiety
      levels in males, but not females, in the early weaning condition. Hippocampal
      changes, which correlated these behavioral responses to imipramine, were seen in
      the extragranule cell layer: the number of calretinin-positive cells was
      increased by imipramine in females, but not in males, in the normal weaning
      condition. In the early weaning condition, however, the treatment was associated
      with similar changes in males but not in females. CONCLUSIONS: The results
      suggest that rearing environment and sex differences are implicated in responses
      to imipramine treatment with respect to anxiety behavior and neurogenesis in the
      hippocampus.

PMID- 22868413
TI  - Gated-SPECT myocardial perfusion imaging and coronary calcium score for
      evaluation of patients with acute chest pain and a normal or nondiagnostic
      electrocardiogram.
AB  - OBJECTIVE: To assess the ability of rest myocardial perfusion imaging (MPI) to
      rule out an acute coronary syndrome (ACS) in emergency department patients, as
      well as to investigate whether there exists a concordance between MPI and
      coronary calcium. MATERIALS AND METHODS: Fifty-five patients with chest pain and
      a normal or nondiagnostic ECG were included. Clinical follow-up was carried out
      within 1 year. RESULTS: Sixteen patients (29%) showed an abnormal rest MPI, and
      in 11 (20%) the MPI was equivocal. There was a weak concordance between MPI and
      coronary arteries calcium score (CACS) (kappa: 0.25). Coronary angiogram driven
      by a positive MPI was performed in 12 patients (23%), resulting in percutaneous
      coronary intervention in nine cases (75%). A positive MPI (abnormal or equivocal
      results) was associated with the occurrence of events in the follow-up
      (chi(2)=19.961, P<0.0001). For a patient presenting to the emergency department
      with acute chest pain and a normal or nondiagnostic ECG, with a positive MPI, the
      relative risk of having events during the first year was 7.5 (95% confidence
      interval: 2.8-19.2), P<0.05, but with a positive CACS this was 1.77 (95%
      confidence interval: 0.69-4.56), P=NS. At 1 year 68.6% of patients were free of
      events. CONCLUSION: Patients presenting with acute chest pain and a low-to
      intermediate likelihood of coronary artery disease with a normal rest MPI have a
      very low probability of cardiac events during the first year. Coronary calcium
      score was not helpful in risk-stratifying these patients.

PMID- 22868414
TI  - [Cardiac surgery for renal failure patients;operative and postoperative
      management].
AB  - Chronic kidney disease( CKD) is defined as one of the major risk factors
      affecting postoperative morbidity and mortality after cardiovascular surgery, and
      CKD accounts for approximately 9.2~13.7% of the patients undergoing
      cardiovascular surgery in Japan according to the reports from Japan Adult
      Cardiovascular Surgery Database (JACVSD). The recent concept on renal
      dysfunction, recent discussions on the choice of operative procedures[ off-pump
      coronary artery bypass grafting( CABG)[OPCAB] vs on-pump CABG, bioprosthesis vs
      mechanical valve prosthesis] and peri-operative managements( electrolyte control,
      pharmacological management) are also introduced in the text.

PMID- 22868415
TI  - [Cardiac surgery for patients with ventricular dysfunction].
AB  - Coronary artery disease and aortic stenosis/regurgitation may cause irreversible
      myocardial damage, resulting in significant heart failure. Although the ultimate
      treatment of the end-stage heart failure is heart transplantation or ventricular
      assist devices, in most cases these patients still have some amount of functional
      and survival benefit by simple surgical treatment such as coronary artery bypass
      grafting (CABG) and valve replacement. However it is associated with significant
      perioperative mortality and morbidity.

PMID- 22868416
TI  - [Cardiac surgery in patients with cerebrovascular disease].
AB  - Cerebral event is the 2nd leading cause of mortality and morbidity after cardiac
      surgery. Therefore, management of cerebrovascular disease is essential to improve
      the outcome. We reviewed the literatures and cases in our institute to present
      the current strategy for these patients. Firstly, for the patients in high risk
      of stroke, if patients undergo coronary artery bypass grafting (CABG), off-pump
      CABG (OPCAB) with aorta non-touch technique is recommended. We experienced no
      intraoperative stroke in our recent consecutive 1,000 cases. If patients require
      cardiopulmonary bypass, keeping blood pressure high during bypass may prevent
      local hypoperfusion in brain. Second, for the patients having carotid artery
      disease, the team approach with neurologists is essential to determine to precede
      either of cardiac surgery or carotid endoarterectomy. Because preceding carotid
      endoarterectomy gives the best result to prevent stroke, these patients had
      better have carotid endoarterectomy first, unless there is indication of urgent
      cardiac surgery. Third, for the patients with active endocarditis, early
      indication of surgery is recently recommended, unless patients have intracranial
      hemorrhage. Recent magnetic resonance imaging (MRI) examination revealed more
      than 60% of patients have stroke regardless of size, therefore, team approach
      with neurologists is important to decide the timing of the surgery. Team approach
      and correct selection of procedural technique are important to prevent
      cerebrovascular events during cardiac surgery.

PMID- 22868417
TI  - [Cardiovascular surgery for patient with pulmonary dysfunction].
AB  - Pulmonary dysfunction is one of the major factors for postoperative pulmonary
      complication. Preoperative pulmonary function test reveals possible operative
      risk. Particularly, in the patient with stage III and IV chronic obstructive 
      pulmonary disease (COPD), open heart surgery with cardiopulmonary bypass is at
      higher risk of complication. In these patients, safe and reliable surgical
      procedures are required. Preoperatively, quitting smoking and incentive
      spirometry can reduce the risk of pulmonary complications. Furthermore,
      noninvasive positive pressure ventilation (NPPV) on the appropriate indication
      can help to improve the outcome in the patients with pulmonary dysfunction.

PMID- 22868418
TI  - [Cardiac and aortic surgery for patient with malignant tumor].
AB  - The management for patients concomitant with malignant tumor and cardiovascular
      disorders( CVD) is an extremely important issue in current era, especially with
      aging of the population. Once the patient planned surgery for neoplasma is also
      required the intervention of CVD, the intervention should be considered a less
      invasive measure as much as possible. Off-pump coronary artery bypass grafting(
      CABG) is more acceptable for the patient with coronary artery disease in this
      consideration than on-pump CABG, and in recommended anti-coagulant issue than
      percutaneous coronary intervention( PCI). Simultaneous surgical measure for both
      non-cardiovascular and cardiovascular diseases is also considered, if the patient
      is in well-tolerated condition. Important is to organize a team between related
      expertise physicians and to decide which way is better for the patient, based on
      a guideline.

PMID- 22868419
TI  - [Atheromatous aorta: clinical pitfall in cardiovascular surgery].
AB  - A highly atheromatous aorta has been reported to bring about devastating
      complications such as endorgan ischemia with or without aortic manipulation. One
      of the complications has been perioperative stroke known that almost the halves
      suffered have been dead even in recent era. The other of the devastating
      complications has been called cholesterol crystal embolization or blue toe
      syndrome, meaning scattered embolization by small cholesterol crystals towards
      splanchnic organs or lower extremities respectively, which has also known to be
      critical. Nowadays, new devices have encouraged cardiovascular clinician to have
      a plan for a safe cardiovascular intervention including aortic manipulation even
      with highly atheromatous aorta. Before the manipulation, modern powerful
      modalities such as transesophageal echocardiography, epiaortic ultrasonography
      and computed tomography (CT), have already become common based on many evidences.
      During operation, evolving techniques and technologies such as off-pump coronary
      artery bypass grafting (OPCAB) and axillary artery cannulation both of which are
      aorta non-touch techniques, which are technically demanding, has proved to reduce
      perioperative stroke recently even though severe complications still occur in
      lower percentages.

PMID- 22868420
TI  - [Cardiac surgery for patients with liver cirrhosis].
AB  - Liver cirrhosis has been shown a major preoperative risk factor in patients
      undergoing cardiac surgery. Although recent evidence comes from limited studies
      with relatively small number of patients, morbidity and mortality progressively
      increase with the severity of liver dysfunction. Patients with Child-Pugh
      classification B or C have significantly higher risks after open heart surgery
      using cardiopulmonary bypass. Recently, model for end-stage liver disease (MELD)
      score more reliably identifies patients who are at higher risk of mortality after
      open heart surgery. Off pump operation seems beneficial to prevent postoperative
      mortality and morbidity in patients with moderate to severe liver dysfunction in
      anecdotally reported cases, but further studies are warranted to prove its
      effectiveness. Incidence of major morbidity including hemodynamic instability
      caused by hyperdynamic circulation, systemic fluid retention, infection, and
      bleeding is high. Preoperative optimization of medical condition by correcting
      coagulopathy, poor nutrition, fluid retention and renal function is important in
      patients with high predictive risks. Non-cardiovascular morbidities including
      malignancies or hepatic decompression are the major limiting factors for long
      term survival. Careful consideration of expected risks and benefits is required
      to determine the surgical indication in those patients.

PMID- 22868421
TI  - [Aortic valve surgery for autoimmune disease].
AB  - Aortic valve disease of autoimmune disease is complicated in pre-, peri- and post
      operative care. Recommended care in aortitis, ankylosing spondylitis, systemic
      lupus erythematosus and rheumatoid arthritis were described. Surgical strategy
      should be determined depending on basic disease, degree of inflammation and
      region of disease. Because of the fragile tissue of autoimmune disease patient,
      modified Bentall procedure is recommended to prevent a prosthetic valve dropping
      off for aortitis. Perioperatively, it is important to control the inflammation of
      basic disease, thus a steroid cover is necessary perioperatively. Some
      complications such as infection, out-of-control of anti-coaguration or gastro
      intestinal bleeding should be avoided. Post operation, a strict follow up of
      prosthetic valve and aorta around suture line and control of autoimmune disease
      should be achieved.

PMID- 22868422
TI  - [Aortic valve surgery for patients with severely calcified aorta].
AB  - Severe atherosclerosis of the ascending aorta frequently causes difficulties
      during heart operations, hindering surgical maneuvers and potentially leading to
      systemic embolism. There have been several methods to solve these problems but
      the best way to treat patients requiring aortic valve replacement (AVR) has not
      been established yet. Surgical techniques for AVR in these patients include AVR
      under deep hypothermic circulatory arrest with or without endarterectomy of the
      ascending aorta or replacement of the ascending aorta. Endovascular clamping
      using a balloon is another approach but requires manipulation of the heavily
      calcified aorta that may result in a certain risk for stroke. Another option to
      avoid the ascending aorta and cross-clamping is the apicoaortic conduit. Recently
      introduced trans-catheter AVR (TAVR), especially trans-apical AVR, has been shown
      to be feasible in such patients. Larger studies and longer follow-up will be
      required to scientifically prove the superiority of trans-apical AVR over
      conventional surgical strategies in patients with porcelain aorta requiring AVR.

PMID- 22868423
TI  - [Aortic dissection with ischemia of the abdominal organs].
AB  - Abdominal organ ischemia associated with aortic dissection is a serious problem,
      although its incidence is not so high. In particular, the prognosis of bowel
      ischemia is extremely poor, especially, in cases with the diagnosis delayed and
      with extensive bowel ischemia. Consequently, 1st it should be suspected, in cases
      with abdominal pain or distension associated with acute or chronic aortic
      dissection. Then, its pathology should be assessed quickly with enhanced computed
      tomography (CT) or ultrasound examination to clarify the mechanism of critical
      organ ischemia including dynamic obstruction or static obstruction of the
      visceral arteries. According to the mechanism of abdominal organ ischemia, the
      best treatment of catheter interventions such as catheter fenestration,
      endovascular aortic repair, and branch-stenting, or of conventional open surgery
      such as surgical abdominal aortic fenestration, graft replacement, and branch
      bypass should be appropriately chosen without delay.

PMID- 22868424
TI  - [Congenital heart disease having left to right shunts combined with pulmonary
      hypertension].
AB  - A large population of patients with congenital heart disease with relevant
      systemic to pulmonary shunts( left to right shunts) will develop pulmonary
      arterial hypertension if left untreated. There are 2 different statuses of an
      increase in pulmonary arterial pressure. One is high resistance due to high
      pulmonary blood flow( high flow with high resistance), another one is low
      pulmonary flow due to high resistance( low flow with high resistance). Chronic
      large left-to-right shunt induced severe pulmonary vascular disease and pulmonary
      hypertension. This was then subsequence of low pulmonary blood flow with high
      pulmonary vascular resistance. We have to avoid this situation and have to do
      intervention while the pulmonary vascular reactivity has been left. Therefore
      accurate diagnosis, preoperative treatment for avoidance of high flow,
      appropriate timing of interventions and post operative various managements are
      important factors as aiming of low pulmonary resistance in this group. It is
      important to be familiar with.

PMID- 22868425
TI  - [Congenital heart surgery in patients with coexisting congenital anomalies of
      respiratory or digestive system].
AB  - Appropriate treatment strategy for congenital heart disease may be influenced by
      coexisting congenital anomalies of respiratory or digestive system. Typical
      congenital anomalies that coexist frequently with congenital heart diseases and
      have influence on treatment strategy of congenital heart disease include
      trecheoesophageal fistula, diaphragmatic hernia, and tracheal stenosis. In
      neonates with congenital heart disease and tracheoesophageal fistula (the
      fistula) should be immediately repaired after birth, followed by cardiac surgery
      to ameliorate heart failure or hypoxemia if feasible. In neonates with congenital
      heart disease and diaphragmatic hernia, diaphragmatic hernia repair is performed
      first unless heart disease is life threatening. In patients with congenital heart
      disease and tracheal stenosis, concomitant repair of heart disease and tracheal
      stenosis is a reasonable strategy in most patients. The treatment of patients
      with congenital heart disease and coexisting congenital anomalies of respiratory
      or digestive system remains challenging. We believe that properly organized
      management by multidiciplinary approach is essential for best achievable outcome.

PMID- 22868426
TI  - [Surgical management of visceral heterotaxy syndrome].
AB  - Surgical management of the heterotaxy syndrome including asplenia or polysplenia
      is still challenging, because they have not only congenital heart defects but
      also gastrointestinal abnormalities. In most cases, they are Fontan candidates,
      however, indications and procedures of surgical strategy toward Fontan operation
      are quite difficult because of cardiac complications or abdominal manifestations.
      We mentioned indications, surgical technique, peri- and post-operative
      managements of asplenia syndrome with our experiences and results.

PMID- 22868427
TI  - [Surgical strategy for pulmonary atresia with ventricular septal defect
      associated with severely hypoplastic or absent central pulmonary artery].
AB  - In patients of pulmonary atresia with ventricular septal defect associated with
      profound hypoplasia or complete absence of central pulmonary artery, surgical
      strategy depends on the morphology of native pulmonary artery and major
      aortopulmonary collateral arteries (MAPCAs). Type of surgery and timing of
      operation are determined by detailed analysis of angiography and 3-dimensional
      computed tomography (3D-CT) scan. When native central pulmonary artery exists,
      palliative procedure like systemicpulmonary shunt or palliative right ventricular
      outflow tract is recommended in order to promote growth of native pulmonary
      artery, followed by Rastelli-type definitive repair with/without uniforcalization
      of MAPCAs. In case of central pulmonary artery absence, staged reconstruction of
      bilateral pulmonary vascular bed by repeated uniforcalization or 1 stage
      uniforcalization and Rastelli operation is indicated. However, even after
      definitive repair, careful attention and scheduled cardiac catheterization with
      aggressive catheter intervention are required to maintain adequate pulmonary
      circulation.

PMID- 22868428
TI  - [Thoracic surgery when the patients have cerebrovascular disease].
AB  - In cancer patients, cerebrovascular disease is recognized as the 2nd most common
      complication involving the central nervous system. Once cancer occurs in stroke
      patients, or vice versa, neurological outcomes significantly worsen and prognosis
      tends to be poor. Perioperative stroke after noncardiac, nonneurosurgical
      procedures is more common than generally acknowledged. It is reported to have an
      incidence of 0.05~7.4% of patients. "The analysis of lung cancer registry for
      resected cases in 1994", jointly established by the Japan Lung Cancer Society and
      the Japanese Association for Chest Surgery, reported a 2.4% frequency of
      cerebrovascular disease. Cerebrovascular disease is an unavoidable comorbidity
      for thoracic surgeons. Most are thrombotic in origin and are noted after
      discharge from the postanesthetic care unit. The mortality is more than 2 times
      greater than in strokes occurring outside the hospital. Delayed diagnosis and a
      synergistic interaction between the inflammatory changes normally associated with
      stroke, and those normally occurring after surgery, may explain this increase.
      Emergency non-contrast scanning of the brain is the primary diagnostic brain
      imaging study for evaluation of patients with suspected stroke, and the goal is
      to complete the computer tomography examination within 25 min of the provisional
      diagnosis being made.

PMID- 22868429
TI  - [Management of patients with arrhythmias undergoing thoracic surgery].
AB  - Recentry, surgical candidates have become older and have more surgical risk
      factors, perioperative patient management become more important than before. In
      the patients with significant arrhythmia observed in the preoperative period,
      examination of the baseline heart disease, i.e. myocardial ischemia or congestive
      heart failure, is mandatory and, if necessary, adequate treatment such as
      defibrillator, the implantation of a pacemaker, anticoagulation therapy, or other
      medical therapy should be performed. In the patients with atrial fibrillation,
      clinical prediction rules such as the congestive heart failure, hypertension,
      age>75, diabetes, previous stroke or transient ischemic attack (TIA) [CHADS 2]
      score have been developed to identify those patients at highest risk for thrombo
      embolism and can be used when assessing the need for bridging anticoagulation by
      heparin prior to surgery. The electrical stimulus from electrocautery may inhibit
      demand pacemakers or may reprogram the pacemaker. An asynchronous or non-sensing
      pacemaker mode is recommended in patients who are pacemaker dependent and whose
      underlying rhythm is unreliable. The device has to be checked to ensure
      appropriate programming and sensing pacing thresholds after surgery. The
      implantable cardioverter defibrillator should be turned off during surgery and
      switched on in the recovery phase before discharge to the ward.

PMID- 22868430
TI  - [General thoracic surgery for patients with coronary artery or aortic disease].
AB  - The incidence of thoracic surgery for patients with arteriosclerosis has
      increased with the aging of society. Pulmonary resection is generally indicated
      for patients with coronary artery or aortic disease, following careful
      preoperative evaluations of cardiopulmonary function and oncological
      resectability. When preoperative coronary revascularization is required,
      percutaneous coronary intervention with a bare metal stent might be effective,
      due to the intermission of antiplatelet therapy during surgery. Furthermore, a"
      non-dissecting" technique that preserves mediastinal adhesion and divides the
      lung parenchyma is an option for pulmonary resection in patients who previously
      underwent coronary arterial bypass grafting (CABG) using the ipsilateral internal
      thoracic artery. Perioperative analgesic management with epidural anesthesia is
      quite important to stabilize  hemodynamics and avoid the use of nonsteroidal anti
      inflammatory drugs, which may influence potential renal dysfunction.
      Postoperative arterial fibrillation, which reduces blood flow in the coronary
      artery with low cardiac output, can be  predicted based on preoperative serum
      brain natriuretic peptide level, and prevented by prophylactic atrial natriuretic
      peptide infusion and immediately controlled with an ultrashort-acting beta
      blocker. Thus, special attention is required for surgical interventions that
      include pulmonary resection in patients with coronary artery or aortic disease.

PMID- 22868431
TI  - [Thoracic surgery for patients with deep vein thrombosis].
AB  - Deep vein thrombosis (DVT) is a main cause of pulmonary thromboembolism (PTE),
      and therefore both diseases are categorized as a serial pathophysiology of venous
      thromboembolism (VTE). Treatment goals for DVT include stopping clot propagation
      and preventing the recurrence of thrombus, the occurrence of PTE, and the
      development of pulmonary hypertension, which can be a complication of multiple
      recurrent pulmonary emboli. Clinical guidelines stratify the risk of VTE to 4
      levels and recommend the treatment options. In high or extremely high risk
      patients for VTE, the use of low-dose heparin is recommended. The prevention
      against VTE, such as elastic compression stockings and intermittent sequential
      pneumatic leg compression( ISPC), is the most important prophylactic treatment
      against perioperative PTE by reducing thrombotic risk in low or moderate high
      risk patients for VET. Since there is no clear evidence that screening all or
      even selected patients for thrombophilias improves long-term outcomes, the
      physician's clinical judgment, and consultation with appropriate subspecialists
      should guide management perioperatively. Once PTE is suspected, immediate and
      accurate diagnosis and appropriate treatment are mandatory.

PMID- 22868432
TI  - [Thoracic surgery for patients with bronchial asthma].
AB  - Thoracic surgery poses a risk for complications in the respiratory system. In
      particular, for patients with bronchial asthma, we need to care for perioperative
      complications because it is well known that these patients frequently have
      respiratory complications after surgery, and they may have bronchial spasms
      during surgery. If we can get good control of their bronchial asthma, we can
      usually perform surgery for these patients without limitations. For safe
      postoperative care, it is desirable that these patients have stable asthma
      conditions that are well-controlled before surgery, as thoracic surgery requires
      intrabronchial intubation for anesthesia and sometimes bronchial resection. These
      stimulations to the bronchus do not provide for good conditions because of the
      risk of bronchial spasm. Therefore, we should use the same agents that are used
      to control bronchial asthma if it is already well controlled. If it is not, we
      have to administer a beta2 stimulator, aminophylline, or steroidal agents for
      good control. Isoflurane or sevoflurane are effective for the safe control of
      anesthesia during surgery, and we should use a beta2 stimulator, with or without
      inhalation, or steroidal agents after surgery. It is important to understand that
      we can perform thoracic surgery for asthma patients if we can provide
      perioperative control of bronchial asthma, although these patients still have
      severe risks.

PMID- 22868433
TI  - [Lung resection for patients with lung cancer and chronic obstructive pulmonary
      disease].
AB  - The number of lung resection for patients with lung cancer has been increasing
      lineally for last two decades in Japan. It reached more than 30,000 in 2009.
      Subsequently those combined with chronic obstructive pulmonary disease (COPD)
      also have increased. As pulmonary vascular bed has already been lost to some
      extent due to chronic alveolar destruction, a careful preoperative physiologic
      assessment according to a guideline by American College of Chest Physicians
      (ACCP) or European Respiratory Society( ERS)/European Society of Thoracic
      Surgeons( ESTS) is important to select patients to be underwent lung resection
      within acceptable risk. The process to evaluate the risk of lung resection for a
      lung cancer patient has three steps structured by forced expiratory volume in 1
      sec( FEV1), diffusion capacitiy for carbon monoxide (DLco), and exercise
      capacity. We suggested that it would be more practical to add global initiative
      for obstructive lung disease( GOLD) staging of each patient and distribution of
      emphysematous lung obtained by functional imaging modarities to the pathway of
      flow chart of the guideline. Some patients with very low FEV1 demonstrate
      increase in FEV1 after lung resection by so called lung volume reduction effect.
      To utilize lots of findings and experiences obtained from lung volume reduction
      surgery( LVRS) contributes to select patients with lung cancer and COPD and to
      perform lung resection and perioperative care properly.

PMID- 22868434
TI  - [Surgical treatment of lung cancer in patients with pulmonary fibrosis].
AB  - Acute exacerbation( AE) of idiopathic pulmonary fibrosis( IPF) is the most common
      cause of postoperative mortality after lung cancer surgery. ostoperative
      mortality rate of lung cancer patients with IPF has been reported to range
      approximately from 3% to 15%. The degree of fibrosis on preoperative high
      resolution computed tomography( CT), preoperative high serum levels of KL-6,
      lactate dehydrogenase(LDH), and C-reactive protein( CRP), and preoperative low
      %TLC, %VC, and %diffusing capacity of CO( DLco) in pulmonary function test have
      been reported as the predictive risk factors for postoperative AE, but the
      clinical relevance remains controversial. Most of reports regarding the 5-year
      survival rate after resection of lung cancer with IPF have been ranged between
      40% and 60%, and significantly poorer than that without IPF. However, considering
      the high risk of AE following chemotherapy or radiotherapy, the poor prognosis
      after surgical treatment can be acceptable. A number of prophylactic strategies
      against AE have been reported in the literature, but none of them has been
      generally established. A nationwide survey concerning postoperative AE after
      resection of lung cancer with pulmonary fibrosis has been conducted in Japan, and
      the final results will be reported soon. Based on the outcomes of the survey,
      standard strategy for the treatment of lung cancer with IPF is expected to be
      established.6.

PMID- 22868435
TI  - [General thoracic surgery and perioperative management in the patients with
      endocrine dysfunction].
AB  - Patients with perioperative endocrine dysfunction represent a particular
      challenge to general thoracic surgeons. This article focuses on the 3 most
      commonly experienced endocrine disorders:diabetes mellitus, thyroid deficiency(
      hyper- and hypothyroidism), and long-term steroid administration. The point is to
      control those endocrine disorders as best as possible before surgery to avoid
      severe perioperative complications. For the patients with uncontrolled endocrine
      disorders who are presenting for elective surgery, their surgical procedures
      should be postponed. Surgeons should understand the clinical condition of their
      patients with endocrine disorders and closely coordinate with endocrinologists
      and anesthesiologists for the appropriate perioperative management. Diabetes
      mellitus is the most common endocrinopathy in patients presenting for surgery.
      Surgeons should be particularly careful for their surgical technique to avoid
      surgical site infection and bronchopleural fistula for diabetic patients
      undergoing lung resection. It is advisable to normalize thyroid function in hyper
      and hypothyroidism because thyroid storm and myxedema coma are severe
      complications and the mortality of them is high. Perioperative steroid
      replacement therapy is necessary for the patients taking steroids according to
      the magnitude of the surgical stress to avoid perioperative hemodynamic
      instability due to adrenal insufficiency.

PMID- 22868436
TI  - [Lung resection for lung cancer patients on hemodialysis].
AB  - Patients on hemodialysis (HD) who undergo lung resection represent a high risk
      group requiring a careful perioperative management. To access a cardiac risk of
      HD patients a complete cardiac examination must be conducted preoperatively. The
      patients should undergo sufficient courses of HD to ameliorate electrolyte
      imbalance and volume disturbance before surgery. An elective operation should be
      scheduled on the day after HD. During operation, gentle operative maneuver and
      complete hemostatic technique are required to reduce a risk of postoperative
      bleeding. An adequate amount of antibiotics should be administrated to avoid a
      surgical site infection. Pulmonary edema due to volume overload and  hyperkalemia
      are the most dangerous postoperative complications. Infusion should be conducted
      with potassium-free solution at 20~40 ml/h until the restart of HD. HD could be
      safely performed with nafamostat mesilate on the day after operation in most
      patients. If hyperkalemia and pulmonary edema are resistant to conservative
      managements, an emergency HD is required. Prognosis after lung resection for lung
      cancer patients on HD is not satisfactory. Many patients die of non cancer
      related causes such as heart failure and infection. Long term management of the
      underlying renal condition is necessary to improve their postoperative survival.

PMID- 22868437
TI  - [Important factors surrounding chest surgery for the patients complicated with
      digestive disease].
AB  - OBJECTIVE: Important factors surrounding chest surgery for the patients
      complicated with digestive disease were discussed according to the experiences of
      clinical settings. METHODS: Check points regarding each context, preoperative,
      perioperative, postoperative, and outpatient care were considered independently.
      RESULTS: If digestive diseases are uncontrolled, the operation should be
      postponed until they are appropriately cared. Dental problems such as teeth
      caries or denture insufficiency should be cleared preoperatively. Dysphagia after
      the head and neck surgery must be evaluated and alternative feeding methods
      should be established. The patients with digestive tract disorder have
      malabsorption and are prone to malnutrition. According to the appropriate
      assessments of digestion and absorption, an enteral nutrition or a total
      parenteral nutrition should be considered before and after operation, to improve
      nutrition status. Immunonutrition is particularly beneficial to reduce the
      postoperative infection or various stresses of invasive operations in the chest
      surgery. Chronic pancreatitis is characterized by absorption impairment and
      pancreatic diabetes. They should also be controlled before the operation using
      digestive enzymes and an exogenous insulin. CONCLUSION: Teeth problems,
      dysphagia, malabsorption, malnutrition and pancreatic diabetes should be assessed
      and cared appropriately before and after the chest surgery using compensative
      therapy.

PMID- 22868438
TI  - [Chest surgery in patients with liver disease].
AB  - Although surgery is contraindicated in patients with acute hepatic disorders such
      as acute hepatitis and acute liver failure, elective surgery might be well
      tolerated to the patients with non-cirrhotic liver diseases. Operative risk in
      patients with liver cirrhosis correlates with the severity of liver damage.
      Several well-known scoring systems for the assessment of cirrhotic severity such
      as Child-Pugh classification might be useful for the risk prediction in major
      abdominal surgery. However, there were few data concerning the risk prediction
      for general non-cardiac thoracic surgery. Clinical manifestations due to liver
      cirrhosis including hypoalbuminemia, bleeding tendency, ascites, infection,
      encephalopathy, should be thoroughly evaluated and optimally treated during
      perioperative period. Furthermore, careful intraoperative procedures are needed
      for both hemostasis and wound healing.

PMID- 22868439
TI  - [Thoracic surgery in patients with autoimmune diseases].
AB  - Autoimmune diseases arise from an inappropriate immune response against
      substances and tissues normally present in the body. Although the pathogenesis
      are still unclear, several autoimmune diseases, such as dermatomyositis, systemic
      sclerosis, have a higher incidence of thoracic neoplasm. Also in the mediastinum
      several autoimmune diseases are known to associate thymoma. While the
      manifestations of the disease diverse, administration of immunosuppressant are
      commonly used for the management of aberrant immune response. Immunosuppressive
      therapies likely to increase susceptibility to infections and associate other
      side-effects, which could increase the risk of surgery and complicate the
      perioperative management. In this article we discuss the autoimmune diseases
      which are known to associate with thoracic and mediastinal neoplasms, and the
      perioperative management of thoracic surgery in patients with autoimmune
      diseases.

PMID- 22868440
TI  - [Surgery for esophageal cancer complicate with cardiovascular disease].
AB  - A risk of cardiac complications is one of the most significant risks to patient
      undergoing major surgery. Especially, for the patients with cancer, the
      preoperative management can be complex. The direct effect of cancer and side
      effect of prior chemotherapy or radiation therapy should be considered. The 2007
      American College of Cardiology/American Heart Association( ACC/AHA) guidelines on
      perioperative cardiovascular evaluation for noncardiac surgery concluded that 3
      elements must be assessed to determine the risk of cardiac event. The
      preoperative risk in a patient is initially assessed by the presence or absence
      of clinical predictors of increased perioperative cardiovascular risk, the
      patient's level of cardiac function, and the underlying risk of the surgical
      procedure. Here we will provide an overview of issue that are relevant to
      patients with esophageal cancer.

PMID- 22868441
TI  - [Esophageal cancer surgery for patients with chronic respiratory diseases].
AB  - Esophageal cancer frequently occurs in the elderly and many of the patients have
      smoking history. Therefore, some of them have pulmonary comorbidity such as
      chronic respiratory diseases. As postoperative pulmonary complications after
      esophagectomy can be a cause of hospital death, careful evaluation is needed
      before the decision of the indication for surgery. In order to prevent
      postoperative pulmonary complications in patients with pulmonary comorbidities,
      modifications in the surgical procedures are needed. Even for cases who can
      tolerate standard esophagectomy, both the bronchial arteries and pulmonary
      branches of the vagal nerve should be preserved as far as possible. For patients
      who cannot tolerate the thoracotomy, transhiatal esophagectomy or non-surgical
      treatment should be selected. Postoperatively, airway cleansing using a
      bronchoscopy or mini-tracheostomy should be performed for cases with difficulty
      in sputum excretion. An enhanced recovery program by multidisciplinary team is
      effective to prevent postoperative pulmonary complications. Perioperative use of
      corticosteroid and sivelestat may reduce the incidence of pulmonary
      complications. As aspiration pneumonia is sometimes fatal in patients after
      esophagectomy, care to avoid aspiration is needed. Respiratory care is essential
      during the follow-up period as well as perioperative period in esophagectomized
      patients with pulmonary comorbidities.

PMID- 22868442
TI  - [Perioperative management of esophageal cancer patients with endocrine or
      metabolic disease].
AB  - Many esophageal cancer patients have endocrine or metabolic diseases, and
      surgeons should therefore learn to manage these conditions in the perioperative
      period. Mortality and morbidity rates are higher in patients with diabetes
      mellitus( DM) than patients without DM, because DM is a risk factor for
      conditions such as ischemic heart disease, chronic renal failure, and
      cerebrovascular disease. Uncontrolled hyperglycemia also increases susceptibility
      to infection and delays wound healing. Preoperative assessment of blood glucose
      control and comorbidities is important in patients with DM. Rapid-acting insulin
      is useful for controlling blood glucose levels in the perioperative period. In
      patients with thyroid disease, surgery is safest at a time when thyroid hormone
      levels are normalized. Patients with adrenocortical insufficiency need
      appropriate perioperative steroid therapy. Surgery for esophageal cancer should
      be undertaken when endocrine and metabolic diseases are well controlled. Strict
      perioperative management is required to prevent complications.

PMID- 22868443
TI  - Accumulation pattern of dehydrins during sugarcane (var. SP80.3280) somatic
      embryogenesis.
AB  - The objective of the present study was to determine dehydrin protein levels in
      sugarcane var. SP80-3280 during somatic embryogenesis. Dehydrins from embryogenic
      and non-embryogenic cell cultures were analyzed using western blot and in situ
      immunolocalization microscopy. Both techniques employ antibodies raised against a
      highly conserved lysine-rich 15-amino acid sequence termed the K-domain, which is
      extensively used to recognize proteins immunologically related to the dehydrin
      family. In embryogenic cultures, western blot analysis of the heat-stable protein
      fraction revealed eleven major bands ranging from 52 to 17 kDa. They were already
      visible on the first days, gradually increasing until reaching peak values around
      day 14, when organogenesis begins, to later decrease in concurrence with the
      appearance of green plantlets (around day 28). These fluctuations indicate that
      this pattern of accumulation is under developmental control. Dehydrins were
      mainly immunolocalized in the nuclei. A phosphatase treatment of protein extracts
      caused a mobility shift of the 52, 49, and 43 kDa dehydrin bands suggesting a
      putative modulation mechanism based on protein phosphorylation. In sugarcane
      embryogenic cultures, presence of dehydrins is a novel finding. Dehydrins were
      absent in non-embryogenic cultures. The novel findings regarding accumulation,
      nuclear localization, and phosphorylation of dehydrins provide a starting point
      for further research on the role of these proteins in the induction and/or
      maintenance of embryogenesis. KEY MESSAGE: The novel findings regarding
      accumulation, nuclear localization, and phosphorylation of dehydrins provide a
      starting point for further research on the role of these proteins in the
      induction and/or maintenance of embryogenesis.

PMID- 22868444
TI  - Corneal endothelial loss after crosslinking with riboflavin and ultraviolet-A.

PMID- 22868445
TI  - Time required for navigated macular laser photocoagulation treatment with the
      Navilas.
AB  - BACKGROUND: Navilas laser is a novel technology combining photocoagulation with
      imaging, including fluorescein angiographic (FA) images which are annotated and
      aligned to a live fundus view. We determine the time necessary for planning and
      treatment of macular edema utilizing the Navilas. METHODS: The screen recordings
      during treatments were retrospectively analyzed for treatment type, number of
      laser shots, the duration of planning (measured from the time the planning image
      was selected to time of marking the last planned treatment spot), and total time
      of laser application. RESULTS: A total of 93 treatments (30 grid, 30 focal and 33
      combined treatments) by four physicians from three sites were included. An
      average of 125 spots were applied to each eye. The total time spent for each
      focal treatment - including the planning was 7 min 47 s (+/-3 min and 32 s).
      CONCLUSIONS: Navilas is a novel device providing a time efficient platform for
      evaluating FA images and performing threshold macular laser photocoagulation.

PMID- 22868446
TI  - Double spiral microchannel for label-free tumor cell separation and enrichment.
AB  - This work reports on a passive double spiral microfluidic device allowing rapid
      and label-free tumor cell separation and enrichment from diluted peripheral whole
      blood, by exploiting the size-dependent hydrodynamic forces. A numerical model is
      developed to simulate the Dean flow inside the curved geometry and to track the
      particle/cell trajectories, which is validated against the experimental
      observations and serves as a theoretical foundation for optimizing the operating
      conditions. Results from separating tumor cells (MCF-7 and Hela) spiked into
      whole blood indicate that 92.28% of blood cells and 96.77% of tumor cells are
      collected at the inner and the middle outlet, respectively, with 88.5% tumor
      recovery rate at a throughput of 3.33 * 10(7) cells min(-1). We expect that this
      label-free microfluidic platform, driven by purely hydrodynamic forces, would
      have an impact on fundamental and clinical studies of circulating tumor cells.

PMID- 22868447
TI  - Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice.
AB  - MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory
      mechanism remains unknown. Here, we explored the role of Spred-2 that negatively
      regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice
      demonstrated exacerbated liver injury, an event that was associated with
      increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the
      control. Levels of CXCL9/CXCL10 that attract and activate these cells were
      increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after
      APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the
      control. Upon stimulation with APAP or IFNgamma, naive Kupffer cells from Spred-2
      KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated
      APAP-hepatotoxicity with lowered hepatic IFNgamma and decreased numbers of not
      only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results
      suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control
      of Kupffer cells and NK cells.

PMID- 22868448
TI  - Comparison of step-wise and ramp-wise incremental rowing exercise tests and 2000
      m rowing ergometer performance.
AB  - PURPOSE: This study examined parameters derived from both an incremental step
      wise and a ramp-wise graded rowing exercise test in relation to rowing
      performance. METHODS: Discontinuous step-wise incremental rowing to exhaustion
      established lactate threshold (LT), maximum oxygen consumption (VO(2maxSTEP)),
      and power associated with VO(2max) (W VO(2max)). A further continuous ramp-wise
      test was undertaken to derive ventilatory threshold (VT), maximum oxygen
      consumption (VO(2maxRAMP)), and maximum minute power (MMW). Results were compared
      with maximal 2000-m ergometer time-trial power. RESULTS: The strongest
      correlation with 2000-m power was observed for MMW (r = .98, P < .001), followed
      by W VO(2max) (r = .96; P < .001). The difference between MMW and W VO(2max)
      compared with the mean of MMW/W VO(2max) showed a widening bias with a greater
      difference coincident with greater power. However, this bias was reduced when
      expressed as a ratio term and when a baseline VO2 was accounted for. There were
      no differences (P = .85) between measures of VO(2maxSTEP) and VO(2maxRAMP);
      rather, the measures showed strong association (r = .97, P < .001, limits of
      agreement = -0.43 to 0.33 L/min). The power at LT and VT did not differ (P = .6),
      and a significant association was observed (r = .73, P = .001, limits of
      agreement = -54.3 to 20.2 W, SEE = 26.1). CONCLUSIONS: This study indicates that
      MMW demonstrates a strong association with ergometer rowing performance and thus
      may have potential as an influential monitoring tool for rowing athletes.

PMID- 22868449
TI  - Intriguing roles of reactive intermediates in dissociation chemistry of N
      phenylcinnamides.
AB  - In mass spectrometry of protonated N-phenylcinnamides, the carbonyl oxygen is the
      thermodynamically most favorable protonation site and the added proton is
      initially localized on it. Upon collisional activation, the proton transfers from
      the carbonyl oxygen to the dissociative protonation site at the amide nitrogen
      atom or the alpha-carbon atom, leading to the formation of important reactive
      intermediates. When the amide nitrogen atom is protonated, the amide bond is
      facile to rupture to form ion/neutral complex 1, [RC(6)H(4)CH=CHCO(+)/aniline].
      Besides the dissociation of the complex, proton transfer reaction from the alpha
      carbon atom to the nitrogen atom within the complex takes place, leading to the
      formation of protonated aniline. The presence of electron-withdrawing groups
      favored the proton transfer reaction, whereas electron-donating groups strongly
      favored the dissociation (aniline loss). When the proton transfers from the
      carbonyl oxygen to the alpha-carbon atom, the cleavage of the C(alpha)-CONHPh
      bond results in another ion/neutral complex 2, [PhNHCO(+)/RC(6)H(4)CH=CH(2)].
      However, in this case, electron-donating groups expedited the proton transfer
      reaction from the charged to the neutral partner to eliminate phenyl isocyanate.
      Besides the cleavage of the C(alpha)-CONHPh bond, intramolecular nucleophilic
      substitution (a nucleophilic attack of the nitrogen atom at the beta-carbon) and
      stepwise proton transfer reactions (two 1,2-H shifts) also take place when the
      alpha-carbon atom is protonated, resulting in the loss of ketene and RC(6)H(5),
      respectively. In addition, the H/D exchanges between the external deuterium and
      the amide hydrogen, vinyl hydrogens and the hydrogens of the phenyl rings were
      discovered by D-labeling experiments. Density functional theory-based (DFT)
      calculations were performed to shed light on the mechanisms for these reactions.

PMID- 22868450
TI  - Ictal intracranial recording from a 'burned-out hippocampus'.
AB  - OBJECTIVE: To present a case involving a discrepancy in the presurgical data of a
      patient suffering from pharmacoresistant mesial temporal lobe epilepsy. CLINICAL
      PRESENTATION AND INTERVENTION: A 47-year-old, female patient with complex partial
      seizures since her twenties came to be evaluated in the Epilepsy Surgery Unit.
      The ictal electroencephalogram suggested a left temporal epileptogenic zone and
      the magnetic resonance image showed an abnormality in the right mesial temporal
      lobe. Intracranial monitoring revealed a pacemaker zone in the right hippocampus
      that discharged fast spreading to the left mesial temporal lobe, a phenomenon
      known as 'burned-out hippocampus'. CONCLUSION: The intracranial recording, even
      though it is an invasive procedure, was necessary for the presurgical evaluation
      of our patient. This case demonstrates the risks of using surface
      electroencephalography to determine localization of epileptogenic zones.

PMID- 22868451
TI  - The effect of C2 substitution on melting point and liquid phase dynamics of
      imidazolium based-ionic liquids: insights from molecular dynamics simulations.
AB  - Using molecular dynamics simulations, the melting points and liquid phase dynamic
      properties were studied for four alkyl-imidazolium-based ionic liquids, 1-n-butyl
      3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), 1-n-butyl-2,3
      dimethylimidazolium hexafluorophosphate ([BMMIM][PF6]), 1-ethyl-3
      methylimidazolium hexafluorophosphate ([EMIM][PF6]), and 1-ethyl-2,3
      dimethylimidazolium hexafluorophosphate ([EMMIM][PF6]), respectively.
      Experimentally it has been observed that the substitution of a methyl group for a
      hydrogen at the C2 position of the cation ring leads to an increase in both the
      melting point and liquid phase viscosity, contrary to arguments that had been
      made regarding associations between the ions. The melting points of the four
      ionic liquids were accurately predicted using simulations, as were the trends in
      viscosity. The simulation results show that the origin of the effect is mainly
      entropic, although enthalpy also plays an important role.

PMID- 22868452
TI  - Ruthenium imidazole oxime carbonyls and their activities as CO-releasing
      molecules.
AB  - Carbon monoxide has been found to possess various beneficial effects in living
      organisms. To study the effects of CO further and to develop potential
      pharmaceutical agents, a meaningful method for delivering CO to the target organ
      is needed. It has been found that under physiological conditions various metal
      carbonyl complexes release carbon monoxide. In this study six novel ruthenium
      carbonyl complexes Ru(IMOX)(CO)(2)(COOR)Cl(1) (IMOX: imidazolecarbaldehyde oxime,
      R: Me, Et) were prepared and tested as carbon monoxide releasing molecules
      (CORMs). Synthesis of the complexes was performed under mild conditions in
      alcoholic solutions. The ability to release CO was tested spectrophotometrically
      by following the transformation of deoxymyoglobin to carbonmonoxy myoglobin. All
      of the complexes studied were found to release CO. Compared to formerly studied
      ruthenium-based CORMs these complexes offer a way for slower CO release.

PMID- 22868453
TI  - Dendritic cell depletion in burn patients is regulated by MafB expression.
AB  - Studies have shown that monocytes are hyporesponsive and that dendritic cells
      (DCs) are depleted in burn patients. We have recently shown in a mouse model that
      burn injury alters the transcriptional regulation in bone marrow progenitors and
      inhibits myeloid-derived DC (mDC) production. In the present study, using human
      burn patient peripheral blood mononuclear cells, we have shown an overexpression
      of MafB with a corresponding reduction in peripheral blood mononuclear cell
      derived mDCs. We isolated mononuclear cells from burn patient (23-68% TBSA) and
      control volunteer peripheral blood samples by Ficoll gradient centrifugation and
      cultured mDCs by using a standard ex vivo culture system. Fluorescence-activated
      cell sorter analysis was used to select myeloid cells based on the cell surface
      expression of CD45+. The mDC fraction was identified by the expression of human
      leukocyte antigen (HLA)-DR+CD11c+, and we found a significant reduction in HLA
      DR+ leukocytes for up to 4 weeks postburn. MafB expression was then examined in
      HLA-DR+CD14+ monocytes. Burn injury alters the phenotype of CD14+ monocytes
      augmenting MafB expression and reducing their differentiation into mDCs. MafB was
      then silenced in ex vivo culture prior to DC differentiation by using small
      interfering RNA technique. MafB gene silencing improved the differentiation
      potential of CD14+ cells into mDCs, increasing the percentage of mDCs by >75%.
      Furthermore, GATA-1+ and HLA-DR+ mDCs were increased following MafB silencing.
      Although burn injury augments the number of peripheral blood monocytes, the
      frequency of mDC is reduced. This impairment is likely secondary to the down
      regulation of mDC differentiation by high MafB-expressing monocytes following
      burn injury.

PMID- 22868454
TI  - Determination of resting energy expenditure after severe burn.
AB  - The purpose of this study was to evaluate the accuracy of nine predictive
      equations for calculating energy expenditure in severely burned adult subjects.
      The selected equations have been reported as commonly used or determined to be
      the most accurate. This prospective, observational study was conducted on adult
      subjects admitted between October 2007 and July 2010 with >= 20% TBSA full
      thickness burns (excluding electrical burns or severe head injury). Indirect
      calorimetry measurements were conducted as a convenience sample during the first
      30 days after injury. Demographic data were collected, and resting energy
      expenditure was calculated using the nine selected predictive equations and
      compared to measured energy expenditure (MEE) using descriptive and comparative
      statistics. Data were collected on 31 subjects with an average age of 46 +/- 19
      years and %TBSA burn of 48 +/- 21%. For all equations, slopes and intercepts were
      significantly different from the line of identity when compared with MEE. A
      calorie-dependent bias was present for all equations, in that lower calorie range
      was overestimated and the higher calorie range was underestimated. Only the
      Carlson and Milner equations had results that were not significantly different
      from the MEE and mean differences that were not significant in all burn size
      ranges. None of the equations had a strong correlation with MEE. Of the equations
      available, the Milner and Carlson equations are the most satisfactory in
      predicting resting energy expenditure in severely burned adults when indirect
      calorimetry is unavailable.

PMID- 22868455
TI  - Apical vertebral derotation in the posterior treatment of adolescent idiopathic
      scoliosis: myth or reality?
AB  - INTRODUCTION: Direct apical vertebral rotation represents an important goal of
      posterior surgery for thoracic adolescent idiopathic scoliosis (AIS), so as to
      obtain a better cosmetic effect and to avoid posterior thoracoplasty. However,
      the real effectiveness in correction of vertebral rotation, using posterior only
      procedures, is still open to debate. The aim of the present study is to compare
      the correction of axial apical rotation obtained with direct rotation procedure
      versus simple concave rod rotation, in patients treated by posterior fusion for
      thoracic AIS using pedicle screw-only construct. MATERIALS AND METHODS: A
      retrospective review was performed on a total of 62 consecutive patients (one
      single institution, three different surgeons) affected by AIS, who had undergone
      a posterior spinal fusion with pedicle screw-only instrumentation between January
      2005 and April 2008 at the reference center. All cases presented a main thoracic
      curve (Lenke type 1 and 2). The angle of rotation (RAsag) of the apical vertebra
      was measured from the preoperative and last follow-up axial CT. According to the
      derotation procedure, two groups were identified: a direct vertebral rotation
      group (DR group; n = 32 patients) and a simple concave rod rotation group (No-DR
      group; n = 30 patients). There were no statistical differences between the two
      groups, in terms of age, Risser's sign, curve patterns, Cobb main thoracic (MT)
      curve magnitude and flexibility, extension of fusion, offset measurements on the
      coronal plane and sagittal preoperative contour. RESULTS: All 62 patients were
      reviewed at an average follow-up of 3.7 years (range 2.5-4.2 years). The DR group
      compared to the No-DR group showed a significantly better final correction of
      apical vertebral rotation (DR 63.4 % vs. No-DR 14.8 %; p < 0.05) and a greater
      final correction (61.3 vs. 52.4 %; p < 0.05) with better maintenance of the
      initial correction (-1.7 degrees  vs. -1.9 degrees ; ns) of the main thoracic
      curve. Concerning the coronal balance, there was the same aforementioned trend of
      better results in the DR group, with less final apical MT vertebra translation
      (DR 2.2 cm vs. No-DR 4.1 cm), greater overall change (preop-final) of lower
      instrumented vertebra (LIV) coronal tilt (-14.9 degrees  vs. -11.1 degrees ; p <
      0.05); the final global coronal balance (C7-S1) resulted quite better in DR
      group, but without a significant difference. The T5-T12 kyphosis angle was quite
      similar in both group before surgery (DR 16.8 degrees  vs. No-DR 17.5 degrees )
      and was little lower at final follow-up evaluation in direct vertebral rotation
      group (14.5 degrees  vs. 16.5 degrees ). The T10-L2 sagittal alignment angle was
      similar in each group before surgery (12.5 degrees  in DR vs. 11.8 degrees  in No
      DR), and at the latest follow-up averaged 5.3 degrees  versus 8.2 degrees ,
      respectively. Lumbar lordosis was similar in each group before surgery (DR -42
      degrees  vs. No-DR -44.1 degrees ) and at the final follow-up evaluation (-45.9
      degrees  vs. -43.2 degrees ). At the latest follow-up, SRS-30 and SF-36 findings
      were similar between the two groups. The complication rate was higher in the
      simple concave rod rotation group (13.3 vs. 9.3 %), related in two cases to
      thoracoplasty, which was never utilized in direct rotation patients. CONCLUSIONS:
      The direct vertebral rotation obtained significantly better final results, when
      compared to simple concave rod rotation, both concerning correction of apical
      vertebral rotation and magnitude of MT curve. On the other hand, the DR group
      presented a little reduction in T5-T12 kyphosis at follow-up, in comparison with
      concave rod rotation procedure. Both procedures were found to be satisfying from
      patients' perspective. Nevertheless overall complication rate was higher in the
      simple concave rod rotation group, related mainly to thoracoplasty (2 cases),
      which was never necessary in direct rotation patients.

PMID- 22868456
TI  - Prevalence of low back pain and factors associated with chronic disabling back
      pain in Japan.
AB  - PURPOSE: This study aimed to report lifetime and 4-week low back pain (LBP)
      prevalence and examine factors associated with chronic LBP and back pain
      disability over a lifetime in a Japanese adult population. METHODS: In February
      2011, 1,063,083 adults aged 20-79 years registered as internet research
      volunteers were randomly selected to participate in a questionnaire survey. The
      data from 65,496 respondents were analyzed to calculate age-standardized lifetime
      and 4-week prevalence. Chronic LBP and back pain disability were defined as LBP
      lasting for >= 3 months and a consecutive >= 4-day-long absence, respectively.
      Factors associated with chronic disabling back pain over a lifetime were examined
      by multiple logistic regression modeling. RESULTS: The lifetime LBP prevalence
      was 83 % and 4-week prevalence was 36 %; majority of the respondents had
      disability-free LBP. Smoking [adjusted odds ratio (aOR): 1.17; 95 % CI: 1.05,
      1.30], lower educational level (aOR: 1.21; 95 % CI: 1.09, 1.34), history of
      disabling back pain among family members and/or significant others (aOR: 1.46; 95
      % CI: 1.27, 1.67), occupational LBP (aOR: 1.34; 95 % CI: 1.16, 1.55), traffic
      injury (aOR: 2.81; 95 % CI: 2.07, 3.81), compensated work injury (aOR: 2.42; 95 %
      CI: 1.92, 3.05), radiating pain (aOR: 4.94; 95 % CI: 4.45, 5.48), low back
      surgery (aOR: 10.69; 95 % CI: 9.02, 12.68), and advice to rest upon back pain
      consultation (aOR: 3.84; 95 % CI: 3.36, 4.40) were associated with chronic
      disabling back pain over a lifetime. CONCLUSIONS: LBP is common in Japan as in
      other industrialized countries. The association between the advice to rest and
      chronic disabling back pain supports recent treatment guidelines emphasizing
      continuation of daily activities.

PMID- 22868457
TI  - Endoscopic excision of C2 Osteoid Osteoma: a technical case report.
AB  - PURPOSE: The Authors illustrate the feasibility of an open biopsy and complete
      excision of Osteoid Osteoma involving the C2 vertebral body performed via
      endoscopic anterior cervical approach. METHODS: A 23-year-old male patient with
      history of delayed diagnosis of cervical Osteoid Osteoma underwent evaluation and
      surgical treatment: the minimally invasive procedure and techniques were
      described. The clinical features, the radiological findings and the outcome were
      assessed. Complications and local recurrences were also recorded. RESULTS: There
      were no intra- or post-operative complications. Immediately after surgery the
      typical Osteoid Osteoma related pain disappeared. At three years follow-up the
      patient was asymptomatic and considered disease-free: CT-scan and x-Ray showed no
      local recurrence and C2-C3 interbody fusion with cervical plate in site.
      CONCLUSIONS: The endoscopic transcervical surgery represents an interesting
      option for the treatment of these diseases in difficult areas of the upper
      cervical spine, also minimizing soft tissue trauma and collateral damage allows
      patients a faster and complete return to normal function. To our knowledge this
      is the first report of cervical spine tumor removal using this minimally invasive
      approach.

PMID- 22868458
TI  - [Examination using multivariate analysis of the risk factors by surgical approach
      in elderly intractable pneumothorax].
AB  - PURPOSE: In this study, we evaluated the risk factors for postoperative
      complications in elderly patients with intractable pneumothorax and constructed a
      risk assessment model. MATERIALS AND METHODS: Between January 2004 and December
      2011, 83 elderly patients( age, 75 years or older) underwent an operation at our
      hospital for intractable pneumothorax. Preoperative factors of these cases were
      assessed to clarify which is contributory to the development of postoperative
      complications by using univariate analysis and multivariate logistic regression
      analysis. RESULTS: Thirty-five patients (42.2%) developed postoperative
      complications. In univariate analysis, total protein, albumin level, blood urea
      nitrogen, creatinine level, Paco2, body mass index, performance status, and
      preoperative respiratory complications showed statistically significant
      associations with the occurrence of postoperative complications. In the
      multivariate analysis, the performance status showed a statistically significant
      association( 95% confidence interval, 1.17~4.44;odds ratio, 2.28;p=0.0157).
      CONCLUSION: The results suggested that the preoperative examinations were useful
      in predicting postoperative complications in the elderly patients with
      intractable pneumothorax. Poor performance status, low nutrition, respiratory
      failure, and preoperative respiratory complications are risk factors for
      postoperative complications in elderly patients with intractable pneumothorax.

PMID- 22868459
TI  - [Distal anastomosis using parachute technique with 4 stay-sutures for Stanford
      type A acute aortic dissection].
AB  - OBJECTIVE: Distal anastomosis in total arch repair for type A acute aortic
      dissection is difficult because of fragile aortic wall and time-limiting
      procedure. Until 2008, distal anastomosis was performed with continuous suture
      technique at 20 C, and parachute technique with 4-stay sutures at 26 C was
      introduced in our institution. This new technique was compared with previous
      distal anastomosis with continuous suture technique. METHODS: From May 1997 to
      December 2010, 40 patients underwent emergent arch repair for type A acute aortic
      dissection. Continuous suture technique was used in 23 patients (group C) and
      parachute technique with 4 stay-sutures was used in 17 patients( group P).
      RESULTS: Patient's demographics did not differ between the 2 groups and there was
      no difference in perioperative or hospital death in the 2 groups. Lower limb
      ischemic time, cardiac ischemic time, cardiopulmonary bypass time and operation
      time were significantly shorter in group P. CONCLUSIONS: Distal anastomosis using
      parachute technique with 4-stay sutures in arch repair for type A acute aortic
      dissection seems to be useful compared with continuous suture technique.

PMID- 22868460
TI  - [Ventricular septation using two-patch technique for total inlet-trabecular
      septal defect].
AB  - A 3-year-old girl underwent ventriclar septation using 2 patch technique.
      Echocardiography at birth revealed single left ventricle with pulmonary
      hypertension. Pulmonary artery banding was performed at the age of 1 month.
      Echocardiography at the age of 3 years showed total inlet-trabecular septal
      defect. Ventricular septation was performed through the right atrium. The tendon
      of Todaro and the coronary sinus were in normal positions. Almost all of the
      inlet septum and trabecular septum were deficit, although the posterior median
      ridge was present. It was considered that the atrio-ventricular node was shifted
      inferiorly and the conduction system ran down the inlet septum as in the case of
      atrioventricular septal defect, since this patient had concordant
      atrioventricular( AV) connection. It was difficult to form the septum using a
      single patch because of complicated anatomy. Thus we decided to divide the patch
      in order to make smooth surface avoiding conduction injury. One patch was used
      for the trabecular defect using running sutures and another patch was used for
      the inlet defect using pledgeted mattress sutures. Eventually both patches were
      sutured together to close the defect. Regular sinus rhythm resumed, although 2:1
      AV block appeared temporally. The patient was discharged at postoperative day 30
      without any complication.

PMID- 22868461
TI  - [Stage IV primary lung cancer treated with lobectomy because of refractory
      ipsilateral pneumothorax].
AB  - A 76-year-old man with dyspnea and left side chest pain was admitted to our
      hospital. Chest roentgenogram showed a left side pneumothorax. Chest computed
      tomography( CT) showed a mass shadow in S3 and a nodular shadow in S10 of left
      lung. Drainage of the pleural cavity and a trans-bronchial biopsy was performed,
      and primary lung adenocarcinoma was diagnosed. Abdominal CT showed a left
      enlarged adrenal gland. Because pneumothorax was resistant to the treatment by
      closed drainage, a surgical treatment was performed. Since the main tumor of left
      upper lobe was adjacent to emphysematous bullae, simple bullectomy was not
      possible. Accordingly, left upper lobectomy, partial resection of left lower lobe
      and lymph node dissection were performed. Positron emission tomography( PET)-CT
      after surgery strongly suggested adrenal gland metastasis and the pathological
      stage IV was established in combination with the histopathological examination.
      Appropriate surgical approach must be considered even for case with the advanced
      lung cancer, like present case.

PMID- 22868462
TI  - [Successful application of cholangioscope as an intravascular endoscope in hybrid
      operation for a child].
AB  - We performed hybrid operation on a 3-year-old boy with thrombosis in the
      pulmonary arterial conduit which had been implanted concomitantly at the time of
      Fontan operation. We used a cholangioscope as a substitute of intravascular
      endoscope. It visualized the organized thrombus and the suture line in the
      conduit. Hybrid operation was successfully performed based on the detailed
      findings gained by cholangioscopy.

PMID- 22868463
TI  - [Video-assisted thoracoscopic extended thymectomy while using the carbon dioxide
      insufflation].
AB  - A 40-year-old woman with generalized myasthenia gravis was scheduled for extended
      thymectomy. The patient under general anesthesia with double-lumen intubation was
      placed in the supine position. A sealed 5 mm trocar and 2 sealed 12 mm trocars
      were inserted through the 3rd, 4th and 5th intercostal space at the both side of
      the anterior axillary line. Under carbon dioxide insufflations by positive
      pressure of 7 mmHg, thymus and fat tissue was resected completely. An operation
      time was 162 minutes, and blood losses during operation were 5 ml. The present
      method was thought to be safe and useful for conducting extended thymectomy.

PMID- 22868464
TI  - [Successful endovascular repair with chimney graft technique and carotid artery
      bypass for ruptured aortic arch aneurysm].
AB  - An 83-year-old man with a decreasing level of consciousness was carried to the
      emergency room. Computed tomography (CT) revealed a ruptured aortic arch
      aneurysm. He was deemed a high risk candidate for conventional surgical repair.
      The case was treated by a hybrid approach. Endo-exclusion of thoracic aortic
      aneurysm (TAA) was obtained by implanting stentgrafts from the ascending to
      descending aorta. The brain circulation was maintained by right to left carotid
      and to left subcravian artery bypasses combined with" chimney endo-debranching
      graft" of the innominate artery. This could be a method of choice for the acute
      patients under similar circumstances.

PMID- 22868465
TI  - [Dilated cardiomyopathy with improved exercise tolerance after cardiac
      resynchronization therapy and mitral valve replacement with bileaflet
      preservation].
AB  - It has been reported that cardiac resynchronization therapy( CRT) improves
      cardiac systolic function and reverses cardiac remodeling by correcting intra-
      and interventricular asynchrony, and that mitral valve replacement (MVR) with
      bileaflet preservation dose not impair left ventricular systolic function through
      preserving the continuity of the mitral complex.The present report describes a
      case of a 68-year-old female with severe chronic heart failure and mitral valve
      regurgitation due to end-stage dilated cardiomyopathy who showed improved
      exercise tolerance following CRT and MVR with bileaflet preservation. Based on
      this case, we considered that the combination therapy of CRT and MVR with
      bileaflet preservation might be one of the effective strategies for severe
      chronic heart failure and mitral valve regurgitation due to end-stage dilated
      cardiomyopathy.

PMID- 22868466
TI  - [Post-renal transplant pulmonary cryptococcosis, which was difficult to
      differentiate from a pulmonary tumor].
AB  - A 61-year-old man, with a history of renal transplant for immunoglobulin A (IgA)
      nephropathy and surgery for advanced gastric carcinoma, was noted to have a
      nodular shadow of 1.3 cm in diameter in the left lung( S8) based on chest
      computed tomography( CT), and was suspected to have primary pulmonary carcinoma
      or a metastatic pulmonary tumor, for which surgical resection was performed. A
      rapid pathological diagnosis of inflammatory granuloma was made, and the patient
      was finally diagnosed as having pulmonary cryptococcosis based on the
      histopathology, and received fluconazole postoperatively. Patients with organ
      transplant history showing a nodular shadow in the lung should undergo a careful
      workup in consideration of both malignant tumor and infection.

PMID- 22868467
TI  - [Pulmonary squamous papilloma].
AB  - We report a rare case of pulmonary squamous papilloma. A 42-year-old woman was
      referred to our hospital complaining of dry cough. A chest computed tomography
      (CT) showed a mass shadow in the lower lobe of left lung. Serum concentrations of
      carcinoembryonic antigen (CEA) and squamous cell carcinoma-related antigen (SCC)
      were elevated to 13.0 ng/ml and 11.8 ng/ml, respectively. The mass was positron
      emission tomography( PET)-positive, with a maximum standard uptake value( SUVmax)
      of 11.55, suggesting a malignant neoplasm. Under the guidance of video-assisted
      thoracoscopy, left basal segmentectomy was performed. Intra-operative diagnosis
      was a squamous papilloma and no malignancy. Her postoperative course was
      uneventful. She is currently alive without any sign of recurrence.

PMID- 22868468
TI  - [Surgical treatment of coarctation of the aorta concomitant with left main
      coronary stenosis; report of a case].
AB  - A 60-year-old male was referred to our institution for investigation of
      intractable hypertension. Coarctation of the aorta was detected by computed
      tomography (CT). Bilateral internal thoracic arteries played an important role as
      a collateral source to the lower extremity. Coronary angiography showed stenosis
      at the ostium of left main trunk. Ascending aorta to bilateral external iliac
      artery bypass grafting and off-pump coronary artery bypass grafting (OPCAB) was
      done simultaneously, this is because we had to harvest left internal thoracic
      artery as a conduit for coronary artery bypass grafting(CABG).Postoperative
      course was uneventful. The patient was discharged 10 days after the operation. We
      could perform less-invasive surgery despite the simultaneous operations.

PMID- 22868469
TI  - [Long-term outcome of the surgical treatment for acute aortic dissection with a
      ringed intraluminal graft; report of a case].
AB  - A 61-year-old female, who had undergone the surgical treatment of acute type A
      aortic dissection with a ringed intraluminal graft 26 years before, presented
      with breathlessness. Computed tomography (CT) showed peri-prosthetic leakage and
      enlargement (45*50 mm in diameter), enlargement of the aortic root (42 mm in
      diameter), and aneurysm of the ascending aorta and the aortic arch (55 mm in
      diameter) with chronic type A aortic dissection. Echocardiography showed severe
      aortic regurgitation. She successfully underwent aortic root replacement( Bentall
      procedure) and total arch replacement.

PMID- 22868470
TI  - [Effusive constrictive pericarditis successfully treated by partial
      pericardiectomy with left thoracotomy; report of a case].
AB  - A 72-year-old male was admitted to our hospital due to high fever and dyspnea.
      Echocardiography and bacterial culture of pericardial fluid revealed purulent
      pericarditis caused by Streptococcus. Despite pericardial drainage and antibiotic
      therapy, hemodynamic instability due to constriction persisted. At 12th hospital
      day, partial pericardiectomy with left thoracotomy was performed. After the
      operation, his hemodynamics improved gradually, and was discharged from the
      hospital on the 54th post operative day without recurrence of infection nor
      constriction.

PMID- 22868471
TI  - [Triple synchronous primary lung carcinomas in the same lobe; report of a case].
AB  - A 78-year-old female was referred to our department due to 3 abnormal shadows in
      the left lower lobe, that were S6, S8 and S10 by chest computed tomography (CT).
      Bronchoscopy was performed, but definitive diagnosis was not obtained. The result
      of surgical biopsy for S10 nodule was squamous cell carcinoma and left lower
      lobectomy with lymph node dissection was performed. Other 2 lesion were both
      adenocarcinoma with mixed subtypes. According to the criteria of Warren and
      Gates, and Martini, these 3 carcinomas were all primary lung cancers.

PMID- 22868472
TI  - [Esophageal duplication cyst resected with video-assisted thorasic surgery;
      report of a case].
AB  - Duplication of the alimentary tract is a developmental anomaly, which may affect
      any part of the digestive tract from the mouth to the anus. Esophageal
      duplication cyst is caused by an incomplete differentiation of the foregut. We
      report a case of esophageal duplication cyst resected using video-assisted
      thoracic surgery (VATS). Chest radiography of a 23-year-old woman showed an
      abnormal shadow. Chest computed tomography (CT) indicated a cystic lesion
      adjacent to the descending aorta and the esophagus. Magnetic resonance imaging
      (MRI) showed that the cystic lesion was filled with protein-rich fluid. The
      lesion was resected using VATS, and it was pathologically diagnosed to be an
      esophageal duplication cyst.

PMID- 22868473
TI  - [Middle mediastinal schwannoma originating from the intrathoracic vagal nerve
      with difficulty in swallowing; report of a case].
AB  - A 41-year-old male complaining of difficulty in swallowing was referred to our
      hospital. Chest computed tomography( CT) demonstrated 34*25*36 mm tumors in the
      subcarinal region. Gadolinium( Gd)-diethylenetriamine pentaacetic acid( DTPA)
      enhanced magnetic resonance imaging (MRI) showed the tumor with the target
      appearance sign, i.e., signal intensity of the mass was low on T1-weighted MRI,
      and the center of the mass was enhanced by Gd-DTPA. A neurogenic tumor was
      suspected on radiological findings. Resection of the tumor by video-assisted
      thoracoscopic surgery was performed. The tumor was found to originate from the
      left vagus nerve by operative findings and was diagnosed as schwannoma by
      pathological examination.

PMID- 22868474
TI  - Optimization of size, morphology and colloidal stability of fluorescein dye-doped
      silica NPs for application in immunoassays.
AB  - Fluorescent nanoparticle (NP) labels are of great interest for point-of-care
      medical diagnostics where high fluorescence signals combined with low limits of
      detection are required. In this work, hydrophilic and hydrophobic fluorescein dye
      derivatives were covalently doped into silica NPs. The NPs were prepared in a
      range of sizes from 16 to 80 nm using both ternary and quaternary microemulsion
      methods where the diameter varied linearly with changes in the water to
      surfactant ratio. The morphology and colloidal stability of the NPs were
      characterised using transmission electron microscopy and photon correlation
      spectroscopy; NPs doped with hydrophobic fluorescein dye were significantly
      smaller and more polydispersed. Optical properties including absorption,
      fluorescence and quantum efficiency were also determined. Representative NPs from
      each microemulsion method (ternary, O = 25 nm and quaternary, O = 80 nm) were
      tested as labels in a fluorescence based immunoassay for the detection of human
      IgG and human chorionic gonadotropin. Both sets of nanoparticle assays showed
      lower limits of detection and better coefficients of variance than a free dye
      label with good day to day reproducibility. The optimal surface coverage of
      detection antibody was also found to depend on the size of the nanoparticle.

PMID- 22868475
TI  - Quantification of p-cresol sulphate in human plasma by selected reaction
      monitoring.
AB  - Chronic renal failure patients accumulate in the blood molecules that are
      normally excreted into the urine. p-Cresol Sulphate (pCS), the most
      representative retained toxin, shows a high level of toxicity. Therefore, its
      quantification could represent a prediction factor to determine the risk of
      endothelial dysfunction and cardiovascular complication and response to the
      haemodialysis treatment. The aim of this study was to evaluate the suitability of
      the multiple reaction monitoring (MRM) technique in order to improve the
      sensibility, the selectivity and the timing of pCS detection in a small amount of
      plasma. Deproteinized plasma of uremic patients was concentrated and dissolved in
      liquid chromatography (LC) mobile phase solution. pCS was quantified by LC
      coupled to tandem mass spectrometry (LC-MS/MS) on a triple-quadrupole mass
      spectrometer. Selective and sensitive detection of pCS was achieved by selecting
      the specific parent ion and monitoring two specific fragment ions. The MRM assay
      was carried out using the following transitions: m/z 187 -> 80.00 and m/z 187 ->
      107.00. A good linearity was observed for each calibration curve. The intra-day
      and inter-day results showed a good precision and repeatability. The percentage
      recoveries indicate an optimal selectivity of the analytical method. The MRM
      assay to quantify pCS in a small amount of human plasma is rapid, highly
      sensitive, selective and with a good repeatability.

PMID- 22868476
TI  - Chemoselective reduction-based fluorescence probe for detection of hydrogen
      sulfide in living cells.
AB  - A selective and sensitive fluorescence probe for hydrogen sulfide (H(2)S)
      detection was synthesized and evaluated in PBS buffer and fetal bovine serum. The
      effect of pH on the probe was also studied. In addition, visualization of H(2)S
      in Hela cells was achieved using confocal laser scanning fluorescence microscopy.

PMID- 22868477
TI  - Selenium speciation in paired serum and cerebrospinal fluid samples.
AB  - Se speciation was performed in 24 individual paired serum and cerebrospinal fluid
      (CSF) samples from neurologically healthy persons. Strong anion exchange (SAX)
      separation, coupled to inductively coupled plasma-dynamic reaction cell-mass
      spectrometry (ICP-DRC-MS), was employed. Species identification was done by
      standard matched retention time, standard addition and by size exclusion
      chromatography followed from SAX (2-D SEC-SAX-ICP-DRC-MS) and by SAX followed
      from CE-ICP-DRC-MS (2-D SAX-CE-ICP-DRC-MS). Limit of detection (LoD, 3*standard
      deviation (SD) of noise) was in the range of 0.026-0.031 MUg/L for all
      investigated species and thus was set uniformly to 0.032 MUg/L. Quality control
      for total Se determination was performed by analysing control materials "human
      serum" and "urine", where determined values met target values. Several Se species
      were found in both sample types having following median values (sequence:
      serum/CSF, each in MUg Se/L): total Se, 58.39/0.86; selenoprotein P (SePP),
      5.19/0.47; Se-methionine (SeM), 0.23/<LoD; glutathione peroxidase (GPx),
      4.2/0.036; thioredoxinreductase (TrxR), 1.64/0.035; Se IV, 12.25/0.046; Se-human
      serum albumin (Se-HSA), 18.03/0.068. Other Se species, such as Se-cystine (SeC),
      Se VI and up to four non-identified compounds were monitored (if ever) only in
      very few samples usually close to LoD. Therefore, their median values were <LoD.
      Linear relationships based on median values provide information about Se-species
      passage across neural barriers (NB): SePP(-serum) is significantly correlated to
      total Se(-serum) when the latter was > 65 MUg/L; however, SePP(-CSF) appeared
      independent of SePP(-serum). For Se-HSA(-serum) versus (vs.) Se-HSA(-CSF), a weak
      linear relationship was found (r(2)=0.1722). On the contrary, for anti-oxidative
      Se-enzymes, higher r (2) values were calculated: GPx(-serum) vs. GPx(-CSF),
      r(2)=0.3837; TrxR(-serum) vs. TrxR(-CSF), r(2)=0.6293. Q(-Se-species) values (=
      ratios of CSF(-Se-species)/serum(-Se-species)) were compared with the Q (-Alb)
      value (HSA(-CSF)/HSA(-serum)=clinical index of NB integrity) for deeper
      information about NB passage of Se species. The Q (-Se-HSA) value (3.8*10(-3))
      was in accordance to the molecular mass dependent restriction at NB (Q(-Alb) at
      5.25*10(-3)). Increased Q values were seen for TrxR (21.3*10(-3)) and GPx
      (8.3*10(-3)) which are not (completely) explained by molecular size. For these
      two anti-oxidative Se-enzymes (GPx, TrxR), we hypothesize that there might be
      either a facilitated diffusion across NB or they might be additionally
      synthesized in the brain.

PMID- 22868478
TI  - Novel plastic biochips for colorimetric detection of biomolecules.
AB  - We report a novel plastic biochip for the sensitive colorimetric detection of
      analytes of interest. This type of biochip is designed to perform bioassays in a
      sandwich format, i.e., employing the immobilized probe molecules to capture
      target and then utilizing gold nanoparticle (AuNP)-labeled reporters to screen
      the biorecognition events. To fabricate and implement such plastic biochips, not
      only have we demonstrated the probe immobilization, sensor unit formation, signal
      transduction and visualization on the plastic substrate, but we have also
      introduced new methods for imaging and analysis of them. As two proof-of-concept
      detection applications, plastic immunochips and DNA biochips have been fabricated
      and their responses to human IgG and DNA have been examined respectively. To
      further assess the detection sensitivity of the colorimetric-based biochip, we
      have compared it with an enzyme-catalyzed-based biochip and with a conventional
      fluorescent-based biochip. We believe the colorimetric-based plastic biochip
      presented herein is able to fully combine the advantage of colorimetric detection
      and plastic substrate, thus making it an ideal platform for point-of-care
      analysis and diagnostics.

PMID- 22868479
TI  - Urinary creatinine concentrations in an industrial workforce and comparison with
      reference values of the general population.
AB  - PURPOSE: Urinary creatinine is an important parameter for the adjustment of
      metabolite concentrations in differently diluted urine specimens, as a reference
      dimension for biological limit or guidance values and as a selection criterion
      for spot urine samples in human biomonitoring. While the creatinine output of the
      general population has been well described in environmental surveys, this study
      focused specifically on creatinine concentrations in a large industrial workforce
      in order to compare these data with the general population and to provide a
      database for the calculation of a reasonable conversion factor between volume
      related and creatinine-adjusted data and vice versa. METHODS: Urinary creatinine
      was analysed in 6,438 spot urine samples by a photometric assay in the time
      period between 1989 and 2009. Basic demographic data (age, sex, body weight, body
      height) and job category (apprentices, skilled craftsmen, skilled chemical
      workers, foremen, laboratory staff and executives) were considered in a
      statistical analysis. RESULTS: The median concentration of urinary creatinine in
      all urine samples was 1.36 g/L with male employees showing significantly higher
      values (1.37 g/L, n = 6,148 samples) than female employees (1.00 g/L, n = 290)
      and concentrations ranging from 0.01 up to 9.76 g/L. Age, body mass index and job
      category were significant influence factors on urinary creatinine. About 92 % of
      all samples showed creatinine concentrations between 0.3 and 3.0 g/L, a range
      recommended by the World Health Organization as a criterion for valid spot urine
      samples. DISCUSSION: The results of this study correspond well with data from
      environmental surveys and with recent data from an active workforce in industry
      with similar sampling strategies. Therefore, a median of 1.4 g creatinine per
      litre urine seems to be a reasonable value for general calculations and
      adjustments. The study data also support the validity of the current
      recommendations by the WHO and several scientific committees and institutions
      with respect to creatinine limits in spot urine samples for occupational-medical
      biomonitoring.

PMID- 22868480
TI  - Wintering in Antarctica: impact on immune response of Indian expeditioners.
AB  - The immune system is one of the major thrust areas in understanding the effects
      of adverse climatic conditions on human health. Exposure to the Antarctic
      environment, such as isolation, cold, UV radiations, magnetic field, blizzards,
      circadian biorhythms, and fear of the unknown, modify various components of the
      immune system. Members of Antarctic expeditions suffer significant emotional
      strain as a result of physical isolation and social deprivation. The present
      study was performed on winter team members of the 28th Indian Scientific
      Expedition. In this study, different immunological parameters, which mainly
      include cytokines (TNF-alpha, IFN-gamma, TGF-beta, and IL-4), chemokine MIP
      1alpha, immunoglobulins (IgA, IgM and IgG), cortisol and netrin-1, were assayed
      in sera by ELISA. Results showed that TNF-alpha and MIP-1alpha levels were
      significantly increased in March, May and August while IFN-gamma levels were
      increased in March and May while TGF-beta levels showed a significant decrease in
      March and May. Serum IgA levels were significantly increased during the entire
      period of the stressful expedition. Therefore, the present study suggests that
      serum IgA could be a potential biomarker for extreme environmental conditions.

PMID- 22868481
TI  - Reliability of the corticospinal tract and arcuate fasciculus reconstructed with
      DTI-based tractography: implications for clinical practice.
AB  - OBJECTIVES: To assess the reliability of diffusion tensor imaging (DTI)-based
      fibre tractography (FT), which is a prerequisite for clinical applications of
      this technique. Here we assess the test-retest reproducibility of the
      architectural and microstructural features of two clinically relevant tracts
      reconstructed with DTI-FT. METHODS: The corticospinal tract (CST), arcuate
      fasciculus (AF) and its long segment (AFl) were reconstructed in 17 healthy
      subjects imaged twice using a deterministic approach. Coefficients of variation
      (CVs) of diffusion-derived tract values were used to assess the microstructural
      reproducibility. Spatial correlation and fibre overlap were used to assess the
      architectural reproducibility. RESULTS: Spatial correlation was 68 % for the CST
      and AF, and 69 % for the AFl. Overlap was 69 % for the CST, 61 % for the AF, and
      59 % for the AFl. This was comparable to 2-mm tract shift variability. CVs of
      diffusion-derived tract values were at most 3.4 %. CONCLUSIONS: The results
      showed low architectural and microstructural variability for the reconstruction
      of the tracts. The architectural reproducibility results encourage the further
      investigation of the use of DTI-FT for neurosurgical planning. The high
      microstructural reproducibility results are promising for using DTI-FT in
      neurology to assess or predict functional recovery.

PMID- 22868482
TI  - Uterine cervical carcinoma: a comparison of two- and three-dimensional T2
      weighted turbo spin-echo MR imaging at 3.0 T for image quality and local-regional
      staging.
AB  - OBJECTIVE: To compare three-dimensional (3D) T2-weighted turbo spin-echo (TSE)
      with multiplanar two-dimensional (2D) T2-weighted TSE for the evaluation of
      invasive cervical carcinoma. METHODS: Seventy-five patients with cervical
      carcinoma underwent MRI of the pelvis at 3.0 T, using both 5-mm-thick multiplanar
      2D (total acquisition time = 12 min 25 s) and 1-mm-thick coronal 3D T2-weighted
      TSE sequences (7 min 20 s). Quantitative analysis of signal-to-noise ratio (SNR)
      and qualitative analysis of image quality were performed. Local-regional staging
      was performed in 45 patients who underwent radical hysterectomy. RESULTS: The
      estimated SNR of cervical carcinoma and the relative tumour contrast were
      significantly higher on 3D imaging (P < 0.0001). Tumour conspicuity was better
      with the 3D sequence, but the sharpness of tumour margin was better with the 2D
      sequence. No significant difference in overall image quality was noted between
      the two sequences (P = 0.38). There were no significant differences in terms of
      the diagnostic accuracy, sensitivity, and specificity of parametrial invasion,
      vaginal invasion, and lymph node metastases. CONCLUSION: Multiplanar
      reconstruction 3D T2-weighted imaging is largely equivalent to 2D T2-weighted
      imaging for overall image quality and staging accuracy of cervical carcinoma with
      a shorter MR data acquisition, but has limitations with regard to the sharpness
      of the tumour margin.

PMID- 22868483
TI  - Optofluidic integrated cell sorter fabricated by femtosecond lasers.
AB  - The main trend in optofluidics is currently towards full integration of the
      devices, thus improving automation, compactness and portability. In this respect
      femtosecond laser microfabrication is a very powerful technology given its
      capability of producing both optical waveguides and microfluidic channels. The
      current challenge in biology is the possibility to perform bioassays at the
      single cell level to unravel the hidden complexity in nominally homogeneous
      populations. Here we report on a new device implementing a fully integrated
      fluorescence-activated cell sorter. This non-invasive device is specifically
      designed to operate with a limited amount of cells but with a very high
      selectivity in the sorting process. Characterization of the device with beads and
      validation with human cells are presented.

PMID- 22868484
TI  - Wireless capsule endoscopy video reduction based on camera motion estimation.
AB  - Wireless capsule endoscopy (WCE) is a novel technology aiming for investigating
      the diseases and abnormalities in small intestine. The major drawback of WCE
      examination is that it takes a long time to examine the whole WCE video. In this
      paper, we present a new reduction scheme for WCE video to reduce the examination
      time. To achieve this task, a WCE video motion model is proposed. Under this
      motion model, the WCE imaging motion is estimated in two stages (the coarse level
      and the fine level). In the coarse level, the WCE camera motion is estimated with
      a combination of Bee Algorithm and Mutual Information. In the fine level, the
      local gastrointestinal tract motion is estimated with SIFT flow. Based on the
      result of WCE imaging motion estimation, the reduction scheme preserves key
      images in WCE video with scene changes. From experimental results, we notice that
      the proposed motion model is suitable for the motion estimation in successive WCE
      images. Through the comparison with APRS and FCM-NMF scheme, our scheme can
      produce an acceptable reduction sequence for browsing and examination.

PMID- 22868485
TI  - Is PCA3 score useful in preoperative staging of a single microfocus of prostate
      cancer diagnosed at saturation biopsy?.
AB  - OBJECTIVE: To evaluate prostate cancer gene 3 (PCA3) score accuracy in
      preoperative staging of cases of single microfocus of prostate cancer (PCa; less
      than 5% with Gleason score <=6) diagnosed after repeat saturation biopsy (median
      30 cores). METHODS: From January 2009 to March 2012, 38 patients (median 64
      years) with a microfocus of PCa, median PSA of 9.1 ng/ml and T1c clinical stage
      underwent radical retropubic prostatectomy. PCA3 score (cut-off of 20 vs. 35) was
      evaluated in predicting insignificant PCa (pIPCa: cancer volume <0.5 ml and
      Gleason score <=6) versus organ-confined (OC) versus non-OC PCa. RESULTS: Median
      PCA3 score results were equal to 10 versus 53 (p < 0.05) versus 108 (p < 0.05) in
      the presence of pIPCa (13.2%), versus OC (65.8%) versus non-OC PCa (21%),
      respectively. PCA3 scores were significantly correlated with tumor volume.
      CONCLUSIONS: A PCA3 score cut-off >20 in the presence of a microfocus of PCa is
      highly predictive of significant PCa (diagnostic accuracy equal to 86.8%) at
      definitive specimen.

PMID- 22868486
TI  - Synthesis and evaluation of thiosemicarbazones functionalized with furyl moieties
      as new chemosensors for anion recognition.
AB  - A family of heterocyclic thiosemicarbazone dyes (3a-f and 4) containing furyl
      groups was synthesized in good yields, characterized and their response in
      acetonitrile in the presence of selected anions was studied. Acetonitrile
      solutions of 3a-f and 4 showed absorption bands in the 335-396 nm range which are
      modulated by the electron donor or acceptor strength of the heterocyclic systems
      appended to the thiosemicarbazone moiety. Fluoride, chloride, bromide, iodide,
      dihydrogen phosphate, hydrogen sulphate, nitrate, acetate and cyanide anions were
      used in recognition studies. From these anions, only sensing features were seen
      for fluoride, cyanide, acetate and dihydrogen phosphate. Two clearly different
      chromo-fluorogenic behaviours were observed: (i) a small shift of the absorption
      band due to the coordination of the anions with the thiourea protons and (ii) the
      appearance of a new red shifted band due to deprotonation. For the latter effect,
      a change in the colour of solution from pale yellow to purple was observed.
      Fluorescence studies were also in agreement with the different effects observed
      in the UV/Vis titrations. In this case, hydrogen bonding interactions were
      visible through the enhancement of the emission band, whereas deprotonation
      induced the appearance of a new red-shifted emission. Logarithms of stability
      constants for the two processes (complex formation + deprotonation) for receptors
      in the presence of fluoride and acetate anions were determined from
      spectrophotometric titrations using the HypSpec V1.1.18 program. Semi-empirical
      calculations to evaluate the hydrogen-donating ability of the receptors and a
      prospective electrochemical characterization of compound in the presence of
      fluoride were also performed.

PMID- 22868487
TI  - Synthesis, X-ray characterization and computational studies of Cu(II) complexes
      of N-pyrazolyl pyrimidine.
AB  - In this manuscript we report the synthesis and X-ray characterization of several
      complexes of Cu(II) with a 2-(1H-pyrazol-1-yl)-pyrimidine (L) ligand. Complexes
      CuLCl(2) (1), [CuL(2)(H(2)O)(2)](NO(3))(2) (2) and [CuL(2)H(2)O](NO(3))(2) (3)
      are mononuclear systems and [CuL(NO(3))(2)](n) (4) is polymeric. In the solid
      state, complexes 2 and 3 are characterized by the presence of anion-pi
      interactions that are relevant for the final 3D architecture and packing. In
      complexes 1 and 4, where the counterion is directly bonded to the metal, anion-pi
      interactions are not observed. High level ab initio calculations (RI-MP2/def2
      TZVP) have been used to evaluate the noncovalent interactions observed in the
      solid state and the interplay between them. We also demonstrate that the presence
      of anions above the aromatic ligand is not due only to strong electrostatic
      interactions between the counterparts.

PMID- 22868488
TI  - Drug nano-domains in spray-dried ibuprofen-silica microspheres.
AB  - Silica microspheres encapsulating ibuprofen in separated domains at the nanometre
      scale are formed by spray-drying and sol-gel processes. A detailed (1)H and (13)C
      NMR study of these microspheres shows that ibuprofen molecules are mobile and are
      interacting through hydrogen bonds with other ibuprofen molecules. (1)H
      magnetisation exchange NMR experiments were employed to characterize the size of
      the ibuprofen domains at the nanometre scale. These domains are solely formed by
      ibuprofen, and their diameters are estimated to be ~40 nm in agreement with TEM
      observations. The nature and formation of these particular texture and drug
      dispersion are discussed.

PMID- 22868490
TI  - Post-electroconvulsive therapy status epilepticus and tardive seizure in a
      patient with rapid cycling bipolar disorder, epilepsy, and intellectual
      disability.
AB  - We describe a case of status epilepticus and tardive seizure after
      electroconvulsive therapy in a patient with rapid cycling bipolar disorder,
      epilepsy, and intellectual disability. This case study illustrates the need of
      careful inquiry of history of seizure while planning electroconvulsive therapy
      and the concomitant use of antiepileptic drugs if warranted especially in
      vulnerable population such as patients with intellectual disability.

PMID- 22868489
TI  - Mechanical efficiency of treadmill running exercise: effect of anaerobic-energy
      contribution at various speeds.
AB  - OBJECTIVES: Mechanical efficiency (ME) describes the ratio between mechanical
      (PMECH) and metabolic (PMET) power. The purpose of the study was to include an
      estimation of anaerobic energy expenditure (AnE) into the quantification of PMET
      using the accumulated oxygen deficit (AOD) and to examine its effect on the value
      of ME in treadmill running at submaximal, maximal, and supramaximal running
      speeds. METHODS: Participants (N = 11) underwent a graded maximal exercise test
      to determine velocity at peak oxygen uptake (vVO2peak). On 4 separate occasions,
      subjects ran for 6 min at speeds corresponding to 50%, 70%, 90%, and 110% of
      vVO2peak. During each testing session, PMET was measured from pulmonary oxygen
      uptake (VO2p) using open-circuit spirometry and was quantified in 2 ways: from
      VO2p and an estimate of AnE (from the AOD method) and from VO2p only. PMECH was
      determined from kinematic analyses. RESULTS: ME at 50%, 70%, 90%, and 110% of
      vVO2peak was 59.9% +/- 11.9%, 55.4% +/- 12.2%, 51.5% +/- 6.8%, and 52.9% +/-
      7.5%, respectively, when AnE was included in the calculation of PMET. The
      exclusion of AnE yielded significantly greater values of ME at all speeds: 62.9%
      +/- 11.4%, 62.4% +/- 12.6%, 55.1% +/- 6.2%, and 64.2% +/- 8.4%; P = .001 (for
      50%, 70%, 90%, and 110% of vVO2peak, respectively). CONCLUSIONS: The data suggest
      that an estimate of AnE should be considered in the computation of PMET when
      determining ME of treadmill running, as its exclusion leads to overestimations of
      ME values.

PMID- 22868491
TI  - Repeated electroconvulsive seizures increase the number of vessel-associated
      macrophages in rat hippocampus.
AB  - OBJECTIVES: We have previously reported that electroconvulsive seizure (ECS)--an
      animal model of the antidepressant treatment electroconvulsive therapy--causes
      glial cell activation in hippocampus and other limbic areas. In the current
      study, we have investigated whether the cellular response to ECS includes
      recruitment and infiltration of nonresident macrophages into the hippocampal
      brain parenchyma. METHODS: Adult rats received 1 ECS daily for 10 consecutive
      days and were then killed at different time points after the last ECS treatment.
      Brain sections were immunostained for laminin, a matrix protein expressed in the
      basal membrane of blood vessels, in combination with anti-CD163, which identifies
      mature blood-borne macrophages. The number of CD163 cells in the hippocampus was
      quantified. We also investigated the number of vessel-associated cells expressing
      CD4 and major histocompatibility complex class II (MHC II). CD4 is mainly
      expressed by CD4 T cells, but can also be found on macrophages, monocytes, and
      activated microglia, whereas MHC II is expressed by macrophages, activated
      microglia, dendritic cells, and B cells. RESULTS: Our results demonstrate
      increased numbers of CD163 and CD4 cells following ECS. Most CD4 cells within the
      vasculature had a similar morphology to the CD163 macrophages. No CD163 cells
      were detected outside the vessels but a subpopulation of CD4 cells was seen in
      the brain parenchyma, here with a morphology resembling microglia. There was a
      transient increase in the number of blood vessel-associated MHC II cells
      following ECS. CONCLUSIONS: Our observations showed that the cellular response to
      ECS involves recruitment of blood-derived macrophages, but we could not see any
      infiltration into the brain parenchyma of these cells.

PMID- 22868492
TI  - Morphometric comparison of foramen magnum in non-syndromic craniosynostosis
      patients with or without Chiari I malformation.
AB  - BACKGROUND: In order to compare the morphometry of foramen magnum (FM) in a
      matched-pair study, in children with non-syndromic craniosynostosis with and
      without Chiari I malformation (CMI), both brain magnetic resonance (MRI) and
      multidetector computed tomography (MDCT) images were utilized. METHODS: Brain MR
      images were retrieved from the Helsinki University Hospital Picture Archiving and
      Communications System to identify patients with CMI during 1.1.2004 to 31.3.2009.
      Age-, gender-, and craniosynostosis-matched controls were retrieved from the same
      cohort. Morphometric analysis of FM was carried out. RESULTS: Seven patients with
      non-syndromic craniosynostosis with CMI were recorded. In CMI patients, the
      absolute anteroposterior length was 33.4 mm as compared to 36.7 mm in controls (p
      = 0.023). The mean width was 28.1 and 29.9 mm (p = 0.29), and the cross-sectional
      area was 654.1 and 764.9 mm(2) (p = 0.11) in CMI and controls, respectively. In
      CMI patients, the relative anteroposterior length of the FM was, on average, 91 %
      of the control's measurements. On average, the width was 95 % and the cross
      sectional area was 88 % of the control's results. CONCLUSIONS: In pediatric non
      syndromic craniosynostosis patients, a statistically significant reduced
      anteroposterior diameter of the FM is found in patients with an adjacent CMI as
      compared to their age-, gender-, and type-matched controls of craniosynostosis.

PMID- 22868493
TI  - Quality of life after transsphenoidal pituitary surgery: a qualitative study.
AB  - BACKGROUND: Microscopic and endoscopic approaches are both utilized for
      transsphenoidal resection of sellar/parasellar lesions. The endoscopic approach
      has been gaining popularity over the past decade; however, quality-of-life
      studies comparing the microscopic and endoscopic approaches are lacking. We aimed
      to compare the patients' perceptions of their postoperative recovery periods
      following microscopic and endoscopic procedures. METHODS: Qualitative research
      methodology was used for this study. Each participant underwent a single semi
      structured, open-ended interview based on an interview guide. Each participant
      had undergone at least one microscopic and one endoscopic transsphenoidal
      procedure for resection of a sellar/parasellar lesion. The interviews were
      audiotaped and transcribed. The transcripts were then analyzed for overarching
      themes. Demographic information was also collected. RESULTS: The following five
      overarching themes emerged from the data: (1) the endoscopic procedure was better
      tolerated than the microscopic procedure and was the preferred approach by 22 out
      of 27 patients should they require another surgery in the future; (2) most
      patients did not know that they had undergone two different surgical approaches;
      (3) other than an unpleasant malodorous smell, rhinologic complications
      (including drainage, crusting, and alterations in smell) following the endoscopic
      procedures were comparable to those following the microscopic procedures; (4) the
      patient's postoperative experience after the microscopic procedure had an impact
      on his/her expectations of the endoscopic procedure; (5) any significant pain or
      discomfort experienced from either procedure was mainly related to the nasal
      packing or fascia lata graft donor site. CONCLUSIONS: The endoscopic procedure
      was the preferred approach over the microscopic approach by the majority of
      patients because of its better tolerability, despite comparable rhinologic
      complications.

PMID- 22868494
TI  - A bayesian optimal foraging model of human visual search.
AB  - Real-world visual searches often contain a variable and unknown number of
      targets. Such searches present difficult metacognitive challenges, as searchers
      must decide when to stop looking for additional targets, which results in high
      miss rates in multiple-target searches. In the study reported here, we quantified
      human strategies in multiple-target search via an ecological optimal foraging
      model and investigated whether searchers adapt their strategies to complex target
      distribution statistics. Separate groups of individuals searched displays with
      the number of targets per trial sampled from different geometric distributions
      but with the same overall target prevalence. As predicted by optimal foraging
      theory, results showed that individuals searched longer when they expected more
      targets to be present and adjusted their expectations on-line during each search
      by taking into account the higher-order, across-trial target distributions.
      However, compared with modeled ideal observers, participants systematically
      responded as if the target distribution were more uniform than it was, which
      suggests that training could improve multiple-target search performance.

PMID- 22868495
TI  - Beneficiary or benefactor: are people more prosocial when they reflect on
      receiving or giving?
AB  - Research shows that reflecting on benefits received can make people happier, but
      it is unclear whether or not such reflection makes them more helpful. Receiving
      benefits can promote prosocial behavior through reciprocity and positive affect,
      but these effects are often relationship-specific, short-lived, and complicated
      by ambivalent reactions. We propose that prosocial behavior is more likely when
      people reflect on being a benefactor to others, rather than a beneficiary. The
      experience of giving benefits may encourage prosocial behavior by increasing the
      salience and strength of one's identity as a capable, caring contributor. In
      field and laboratory experiments, we found that participants who reflected about
      giving benefits voluntarily contributed more time to their university, and were
      more likely to donate money to natural-disaster victims, than were participants
      who reflected about receiving benefits. When it comes to reflection, giving may
      be more powerful than receiving as a driver of prosocial behavior.

PMID- 22868496
TI  - Reading between the minds: the use of stereotypes in empathic accuracy.
AB  - An ideal empathizer may attend to another person's behavior in order to
      understand that person, but it is also possible that accurately understanding
      other people involves top-down strategies. We hypothesized that perceivers draw
      on stereotypes to infer other people's thoughts and that stereotype use increases
      perceivers' accuracy. In this study, perceivers (N = 161) inferred the thoughts
      of multiple targets. Inferences consistent with stereotypes for the targets'
      group (new mothers) more accurately captured targets' thoughts, particularly when
      actual thought content was also stereotypic. We also decomposed variance in
      empathic accuracy into thought, target, and perceiver variance. Although past
      research has frequently focused on variance between perceivers or targets (which
      assumes individual differences in the ability to understand other people or be
      understood, respectively), the current study showed that the most substantial
      variance was found within targets because of differences among thoughts.

PMID- 22868497
TI  - Hemophagocytic macrophages in murine typhoid fever have an anti-inflammatory
      phenotype.
AB  - Histiocytes are white blood cells of the monocytic lineage and include
      macrophages and dendritic cells. In patients with a variety of infectious and
      noninfectious inflammatory disorders, histiocytes can engulf nonapoptotic
      leukocytes and nonsenescent erythrocytes and thus become hemophagocytes. We
      report here the identification and characterization of splenic hemophagocytes in
      a natural model of murine typhoid fever. The development of a flow-cytometric
      method allowed us to identify hemophagocytes based on their greater than 6N
      (termed 6N+) DNA content. Characterization of the 6N+ population from infected
      mice showed that these cells consist primarily of macrophages rather than
      dendritic cells and contain T lymphocytes, consistent with hemophagocytosis. Most
      6N+ macrophages from Salmonella enterica serovar Typhimurium-infected mice
      contain intact DNA, consistent with hemophagocytosis. In contrast, most 6N+
      macrophages from control mice or mice infected with a different bacterial
      pathogen, Yersinia pseudotuberculosis, contain damaged DNA. Finally, 6N+ splenic
      macrophages from S. Typhimurium-infected mice express markers consistent with an
      anti-inflammatory M2 activation state rather than a classical M1 activation
      state. We conclude that macrophages are the predominant splenic hemophagocyte in
      this disease model but not in Y. pseudotuberculosis-infected mice. The anti
      inflammatory phenotype of hemophagocytic macrophages suggests that these cells
      contribute to the shift from acute to chronic infection.

PMID- 22868498
TI  - Accumulation of myeloid-derived suppressor cells in the lungs during Pneumocystis
      pneumonia.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      hematopoietic precursors with the ability to adversely affect host immunity. They
      have been shown to accumulate in pathological conditions, such as cancer and some
      microbial diseases. In the mouse and rat models of Pneumocystis pneumonia (PcP),
      we found a distinct population of cells with MDSC-like morphology in the
      bronchoalveolar lavage (BAL) fluid, constituting up to 50% of the total cells in
      BAL fluid. These cells were not seen in the BAL fluid from normal animals or from
      Pneumocystis-infected animals that had been successfully treated for PcP with a
      combination of trimethoprim and sulfamethoxazole. With flow cytometry, these
      cells were found to express the characteristic MDSC surface markers Gr-1 and
      CD11b in mice or CD11bc and His48 in rats. Using reverse transcription-PCR, we
      demonstrated that these cells produced high levels of arginase-1 and inducible
      nitric oxide synthase (iNOS) mRNA. These cells were shown to suppress CD4(+) T
      cell proliferation in response to stimulation by anti-CD3 and anti-CD28
      antibodies. Adoptive transfer of these cells to normal mice caused lung damage,
      as indicated by elevated levels of albumin and lactate dehydrogenase in the BAL
      fluid. These experiments provide evidence of the presence of MDSCs in the lungs
      during PcP. Further studies on the roles of MDSCs in PcP are warranted in order
      to develop treatment strategies which can reduce the number of MDSCs and the
      damage caused by these cells.

PMID- 22868500
TI  - Conclusions on motor control depend on the type of model used to represent the
      periphery.
AB  - Within the field of motor control, there is no consensus on which kinematic and
      kinetic aspects of movements are planned or controlled. Perturbing goal-directed
      movements is a frequently used tool to answer this question. To be able to draw
      conclusions about motor control from kinematic responses to perturbations, a
      model of the periphery (i.e., the skeleton, muscle-tendon complexes, and spinal
      reflex circuitry) is required. The purpose of the present study was to determine
      to what extent such conclusions depend on the level of simplification with which
      the dynamical properties of the periphery are modeled. For this purpose, we
      simulated fast goal-directed single-joint movement with four existing types of
      models. We tested how three types of perturbations affected movement trajectory
      if motor commands remained unchanged. We found that the four types of models of
      the periphery showed different robustness to the perturbations, leading to
      different predictions on how accurate motor commands need to be, i.e., how
      accurate the knowledge of external conditions needs to be. This means that when
      interpreting kinematic responses obtained in perturbation experiments the level
      of error correction attributed to adaptation of motor commands depends on the
      type of model used to describe the periphery.

PMID- 22868499
TI  - The Asd(+)-DadB(+) dual-plasmid system offers a novel means to deliver multiple
      protective antigens by a recombinant attenuated Salmonella vaccine.
AB  - We developed means to deliver multiple heterologous antigens on dual plasmids
      with non-antibiotic-resistance markers in a single recombinant attenuated vaccine
      strain of Salmonella enterica serotype Typhimurium. The first component of this
      delivery system is a strain of S. Typhimurium carrying genomic deletions in alr,
      dadB, and asd, resulting in obligate requirements for diaminopimelic acid (DAP)
      and d-alanine for growth. The second component is the Asd(+)-DadB(+) plasmid pair
      carrying wild-type copies of asdA and dadB, respectively, to complement the
      mutations. To evaluate the protection efficacy of the dual-plasmid vaccine, S.
      Typhimurium strain chi9760 (a strain with multiple attenuating mutations:
      Deltaasd Deltaalr DeltadadB DeltarecF) was transformed with Asd(+) and DadB(+)
      plasmids specifying pneumococcal antigens PspA and PspC, respectively. Both
      plasmids were stable in chi9760 for 50 generations when grown in nonselective
      medium. This was significantly (P < 0.05) greater than the stability seen in its
      recF(+) counterpart chi9590 and could be attributed to reduced interplasmid
      recombination in chi9760. Oral immunization of BALB/c mice with 1 * 10(9) CFU of
      chi9760 (carrying Asd(+)-PspA and DadB(+)-PspC plasmids) elicited a dominant Th1
      type serum IgG response against both antigens and protected mice against
      intraperitoneal challenge with 200 50% lethal doses (LD(50)s) of virulent
      Streptococcus pneumoniae strain WU2 or intravenous challenge with 100 LD(50)s of
      virulent S. pneumoniae strain L81905 or intranasal challenge with a lethal dose
      of S. pneumoniae A66.1 in a pneumonia model. Protection offered by chi9760 was
      superior to that offered by the mixture of two strains, chi9828 (Asd(+)-PspA) and
      chi11026 (DadB(+)-PspC). This novel dual-plasmid system marks a remarkable
      improvement in the development of live bacterial vaccines.

PMID- 22868501
TI  - Alveolar soft part sarcoma: should we be targeting the tumor or targeting the
      vasculature?

PMID- 22868502
TI  - Anthracycline-induced cardiotoxicity: cardiac monitoring by continuous wave
      Doppler ultrasound cardiac output monitoring and correlation to echocardiography.
AB  - BACKGROUND: Anthracyclines are agents with a wellknown cardiotoxicity. The study
      sought to evaluate the hemodynamic response to an anthracycline using realtime
      continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and
      echocardiography in combination with serum biomarkers. METHODS: 50 patients (26
      male, 24 female, median age 59 years) suffering from various types of cancer
      received an anthracycline-based regimen. Patients' responses were measured at
      different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1
      day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4)
      and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume
      (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro
      BNP and hs-Troponin T (T0-T4). RESULTS: During the 3-month observation period,
      the relative decrease in the EF determined by echocardiography was -2.1% (?T0-T4,
      T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed
      using CW-Doppler was -6.5% (?T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p =
      0.14). The kinetics for serum biomarkers were inversely correlated. CONCLUSIONS:
      Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for
      monitoring the immediate and chronic hemodynamic changes during an anthracycline
      based regimen; the results obtained were comparable to those from
      echocardiography.

PMID- 22868503
TI  - Efficacy of trabectedin in patients with advanced or metastatic alveolar soft
      part sarcoma.
AB  - BACKGROUND: Alveolar soft-part sarcoma (ASPS) is a rare sarcoma often occurring
      in young patients that is characterized by the unbalanced translocation
      der(17)t(X;17) (p11;q25). Although it usually shows an indolent clinical course,
      the prognosis is usually poor in advanced disease. Since standard chemotherapy
      regimens used in soft-tissue sarcomas lack efficacy in ASPS, new therapeutic
      options are needed. We investigated the efficacy of trabectedin, which has
      demonstrated activity in a variety of cancer types including some of the most
      prevalent translocation-related sarcomas. PATIENTS AND METHODS: 7 patients with
      metastatic or advanced ASPS treated with trabectedin in the Sarcoma Center Berlin
      Brandenburg and the University Hospital of Greifswald were analyzed for median
      progression-free survival (mPFS), overall survival (OS), and therapy-related
      toxicity. RESULTS: In 6 patients with documented disease progression, disease
      stabilization was reached with trabectedin; only 1 patient experienced
      progressive disease. The mPFS and OS were 7 months and 21 months, respectively,
      since the start of trabectedin treatment. Overall, no severe Common Toxicity
      Criteria (CTC) grade 3 or 4 toxicity was observed. CONCLUSIONS: The poor
      prognosis of patients with ASPS has so far been due to the unavailability of
      effective systemic treatments. Trabectedin can be considered the only currently
      registered drug with clinical activity in this disease.

PMID- 22868504
TI  - Phase II study of loading-dose ibandronate treatment in patients with breast
      cancer and bone metastases suffering from moderate to severe pain.
AB  - BACKGROUND: The aim of this study was to determine the efficacy and safety of
      loading-dose intravenous (i.v.) ibandronate in women with breast cancer and bone
      metastases. PATIENTS AND METHODS: In this prospective, phase II, open-label
      study, 13 women with breast cancer, bone metastases, and moderate/severe bone
      pain received ibandronate 6 mg/day (i.v. loading-dose 15 min infusion over 3
      consecutive days) with follow-up until day 14. Endpoints included pain response
      (primary), duration until pain response, analgesic use, Karnofsky index, safety
      (including hematologic, biochemical, and urine examinations), and adverse events.
      RESULTS: Pain intensity decreased on days 7 and 14 versus day 1 (mean visual
      analogue scale score: 3.2 +/- 2.2 and 3.0 +/- 2.1 versus 6.1 +/- 0.9,
      respectively; p < 0.01 for both). Mean time to pain response was 8.2 +/- 3.3
      days. Mean rate of analgesic use decreased (69.2%, 16.7% and 15.4% on days 1, 7
      and 14, respectively). Mean Karnofsky index score increased (80.8 +/- 13.1 and
      80.8 +/- 13.2, on days 7 and 14 versus 77.7 +/- 11.7 on day 1; p < 0.05 on both
      days). CONCLUSION: Bone pain and analgesic use decreased in women with breast
      cancer and bone metastases following loading dose i.v. ibandronate which was well
      tolerated with no renal safety concerns.

PMID- 22868505
TI  - Localization of PKCeta in cell membranes as a predictor for breast cancer
      response to treatment.
AB  - BACKGROUND: Successful treatment of breast cancer is frequently limited by the
      resistance of tumors to chemotherapy. Recent studies suggested a role for protein
      kinase C (PKC) in the resistance to chemotherapy. Here we used retrospective
      analysis of breast cancer biopsies of neoadjuvantly treated patients to
      investigate the correlation of PKC expression with aggressiveness and resistance
      to chemotherapy. PATIENTS AND METHODS: Our cohort (n = 25) included patients with
      advanced and aggressive breast cancers, who underwent neoadjuvant therapy with
      the CAF regimen (cyclophosphamide, doxorubicin, fluorouracil). Core biopsies (pre
      chemotherapy) and surgical biopsies of primary tumors and lymph node metastases
      (post-chemotherapy) were scored for PKCeta (PKCh) and PKCepsilon (PKCe)
      expression in the cytoplasm, cell membrane, nuclear membrane, and the nucleus.
      RESULTS: Our results showed increased expression of PKCh (not PKCe) in the
      cytoplasm and cell membranes of post-chemotherapy biopsies (p = 0.03). PKCh
      presence in cell membranes, indicating activation, was in correlation with poor
      survival (p = 0.007). CONCLUSION: PKCh staining in cell and nuclear membranes is
      an indicator for poor survival and a predictor for the effectiveness of
      neoadjuvant treatment. Other avenues of treatment should be considered for these
      patients. PKCh presents a target for therapy where inhibition of its activity
      and/or translocation to membranes could interfere with the resistance to
      chemotherapy.

PMID- 22868506
TI  - Human leukocyte antigen (HLA)-DRB1*14 is associated with a high incidence of
      acute lymphocytic leukemia.
AB  - BACKGROUND: Genetic background and environmental factors play an interactive role
      in the development of acute lymphocytic leukemia (ALL), and the human leukocyte
      antigen (HLA) system was noted as an important genetic factor in ALL. MATERIAL
      AND METHODS: Due to the high diversity of HLA alleles, our present study assessed
      the possibility of an association of HLA molecules in ALL patients living in
      Jiangsu Province, Eastern China. HLAA, -B, and -DRB1 allele distributions in 156
      ALL patients (aged 3-54 years) were analyzed and compared with unrelated healthy
      hematopoietic stem cell donors from the same ethnic and geographic background.
      RESULTS: No significance was found at HLA-A, -B loci between the ALL group and
      the control group. However, a significant difference was discovered at HLA
      DRB1*14 (8.65% in the ALL group versus 4.8% in the control group, pC < 0.05),
      with an odds ratio of 1.87 (95% confidence interval 1.26- 2.80). CONCLUSION: HLA
      DRB1*14 may be associated with susceptibility to ALL acquisition among the
      Jiangsu Han population.

PMID- 22868507
TI  - Cerebral metastases of an endometrial stromal sarcoma: report of the first case.
AB  - BACKGROUND: Endometrial stromal sarcomas (ESSs) of the uterus are rare
      gynecological malignancies. Common locations of distant metastases are vagina,
      vulva, lung, mediastinum, abdomen, bones and ovaries. CASE REPORT: We present the
      case of a 69-year-old woman with a Federation of Gynecology and Obstetrics (FIGO)
      IIb (classification 2009) ESS of the uterus of high-grade malignancy. Initially,
      a hysterectomy Piver II and total colpectomy were performed, followed by pelvic
      field irradiation. 8 months later, the patient suffered seizures and hemiparesis.
      A computed tomography (CT) scan revealed cerebral metastases, and irradiation of
      the brain was initiated. After completion of the staging examinations, additional
      metastases of lung, abdomen, mediastinum, vulva and inguinal lymph nodes were
      found. This is the first reported case of brain metastases of an ESS. CONCLUSION:
      Appropriate treatment options like surgery, chemotherapy or endocrine therapy
      should be discussed on an individual basis since large-scale clinical trials have
      not yet been conducted in this rare entity.

PMID- 22868508
TI  - Successful treatment of mediastinal seminoma in a hemodialysis patient.
AB  - BACKGROUND: Extragonadal germ cell tumors (GCTs) are relatively uncommon
      neoplasms, affecting primarily men during the third and fourth decades of life.
      CASE REPORT: We describe an unusual case of mediastinal seminoma in a 21-year-old
      male on chronic peritoneal dialysis for renal failure of uncertain etiology. The
      patient was treated with chemotherapy consisting of etoposide and cisplatin (EP)
      combined with hemodialysis. Cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2))
      were given on days 1, 3, and 5 for induction. Hemodialysis was started 1 h after
      completion of etoposide infusion. Following this course of treatment, another 4
      cycles of cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2)) were given on
      successive days from day 1 to 5. Hemodialysis was carried out daily, prior to the
      start of chemotherapy. Subcutaneous PEG-filgrastim was given on day 6 in all
      cycles. The patient's status after the first post-induction treatment was
      complicated by a pseudomonas infection. Tumor response to chemotherapy was prompt
      with remission lasting to date, 17 months after diagnosis. CONCLUSION: This case
      report is the second description of chemotherapy given to a hemodialysis patient
      with extragonadal GCT. We suggest that treatment with EP combined with
      hemodialysis according to the presented protocol is feasible, and may result in a
      favorable outcome.

PMID- 22868509
TI  - Long-term disease stabilization in a patient with castration-resistant metastatic
      prostate cancer by the addition of lenalidomide to low-dose dexamethasone and
      celecoxib.
AB  - BACKGROUND: Treatment of castration-resistant prostate cancer (CRPC) remains a
      challenge considering that most patients are elderly men with significant
      comorbidities. Alternative treatment strategies to cytotoxic therapy should be
      explored. There is evidence that the continuous administration of cyclooxygenase
      2 (COX2) inhibitors and the immunomodulatory agents thalidomide or lenalidomide
      can result in longterm disease stabilization. CASE REPORT: A 70-year-old patient
      with castration-resistant metastatic prostate cancer was treated with a
      combination of low-dose dexamethasone, celecoxib and subsequently lenalidomide.
      The patient had longterm disease stabilization for 33 months and a very good
      performance status despite moderate side effects, i.e. moderate Cushing's
      syndrome and mild laboratory hematologic toxicity. CONCLUSION: The addition of
      lenalidomide to low-dose dexamethasone and celecoxib resulted in an impressive
      longterm disease stabilization of CRPC in this patient, allowing him to lead an
      active life with a good quality of life.

PMID- 22868510
TI  - Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin.
AB  - BACKGROUND: Heavily treated Wilms' tumor responding to the combination of
      paclitaxel and carboplatin has not yet been reported. CASE REPORT: A 17-year-old
      man presented with hematuria. He received a diagnosis of Wilms' tumor with
      multiple lung metastases and was treated with preoperative chemotherapy including
      vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant
      chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he
      suffered from 4 relapses and has been treated with multiple anticancer agents
      including high-dose chemotherapy with autologous peripheral blood stem cell
      transplantation. Finally, the disease progressed due to peritoneal and pleural
      metastases. With opioid administration for left shoulder pain due to pleural
      metastasis, he received combination chemotherapy with carboplatin (area under the
      curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a
      partial response with mild toxicity. He received 7 cycles of the chemotherapy and
      the time to progression was 200 days. CONCLUSION: In a refractory case after
      intensive treatments, we succeeded to control the disease for a while.

PMID- 22868511
TI  - Radiotherapy for head and neck cancer: an increasing dependence on innovative
      imaging.
AB  - Technical improvements in computed tomography and magnetic resonance imaging as
      well as the wider availability of biological imaging have facilitated the
      implementation of high-precision 3-dimensional conformal and intensity-modulated
      radiotherapy (RT) in head and neck cancer. The integration of recent advances in
      functional and molecular imaging has already improved RT delivery, response
      prediction, and follow-up. Rational clinical use of all modalities should be
      encouraged, especially in the setting of imaging-intensive investigational RT
      protocols such as adaptive therapy. An expanded development of imaging markers
      that can predict radioresistance or outcome could further customize treatment.
      The continued successful use of innovative imaging in routine clinical practice
      will ultimately depend on well-designed clinical studies with adequate follow-up.

PMID- 22868512
TI  - First-line therapy of mutated non-small cell lung cancer: an update.
AB  - Currently, many treatment options and new targets for cancer therapies for
      patients with advanced non-small cell lung cancer (NSCLC) are being evaluated.
      This article discusses in detail the significance of first-line and second-line
      epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and
      inhibitors of the vascular endothelial growth factor receptor (VEGFR) and EML4
      ALK. Furthermore, the article summarizes the implications and future prospects of
      using molecular testing in the field of NSCLC with focus on EGFR mutations, KRAS
      mutation, EML4-ALK fusion gene detection, and EGFR expression.

PMID- 22868513
TI  - Well-differentiated hand liposarcoma with bone metastases treated successfully
      with zoledronic acid: a molecular mechanism.

PMID- 22868514
TI  - [Drug allergy].

PMID- 22868515
TI  - [Measurement of alveolar nitric oxide levels in the management of asthma].

PMID- 22868516
TI  - [Long-term management of child asthma].

PMID- 22868517
TI  - [Biology of proteasomes discovery in immuno-typed proteasomes and their roles in
      molecular immunity].

PMID- 22868518
TI  - [Heterogeneity of human mast cells].

PMID- 22868519
TI  - [Induction of allergic responses mediated by invariant iNKT].

PMID- 22868521
TI  - [Flow and inspiratory pressure characteristics of In-Check(tm) and training
      whistles].
AB  - BACKGROUND: The optimal inhalation effort using dry powder inhalers (DPI's)
      varies with the specific inhaler. Accordingly, the device used for instruction in
      the proper use of the specific DPI should have physical characteristics similar
      to the actual DPI. However, the precision with which these devices mimic the
      actual DPI's has not been established. METHODS: We measured mouthpiece pressure
      (PI) and flow through the In-Check with an added flow resistance (for DiskusTM,
      DiskhalerTM, PulmicortTM, HandihalerTM, and ClickhalerTM) and the training
      whistles (for Diskus, Pulmicort, SymbicortTM, TwisthalerTM) at different
      inhalation pressures. RESULTS: Both the In-Check with an added flow resistance
      for individual DPI and the training whistles for each DPI had parabolic PI-flow
      relationships similar to the actual DPI. When a curve was drawn from direct
      readings of the In-Check scale, it fell consistently below that based on the
      pneumotachometer values. PI-flow curves of the actual DPI fell below both of the
      above curves. Among the same type of DPI, PI-flow relationships resembled each
      other, but one of 13 in the Diskus group demonstrated curves above and one of 6
      in Pulmicort demonstrated curves below the others. The flows at which sounds were
      generated from the whistle were between 25-50 L/min. CONCLUSIONS: Both In-Check
      and training whistles had suitable PI-flow relationships. Flow readings taken
      directly from In-Check tended to be lower than the measured value. A few training
      whistles might generate sounds with efforts below the optimal one.

PMID- 22868520
TI  - [Mast cell regulation].

PMID- 22868522
TI  - [Clinical effects of budesonide/formoterol combination drug in elder patients
      with asthma compared with budesonide plus tulobuterol patch combination
      treatment].
AB  - BACKGROUND AND AIMS: Tulobuterol patch (Tulo) is often used for treatment of
      elder patient with asthma in Japan. However, there is no evidence either ICS plus
      Tulo or ICS/LABA combination is better for elder patient. METHODS: Elder patients
      with asthma (aged>= 70, n=17) who had treated with budesonide (BUD) 400 MUg/day
      plus Tulo 2 mg/day, were randomly assigned either to change control medication to
      budesonide/formoterol combination (BUD/FM) 320/9 MUg/day or to keep BUD plus Tulo
      treatment for 12 weeks. RESULTS: At week 4 and week 12, the BUD/FM group showed
      significant increase in lung function (FEV1, %FEV1) and mini AQLQ score compared
      with the BUD plus Tulo group. The BUD/FM group also showed decrease in Tumor
      Necrosis Factor-alpha level in exhaled breath condensate at week 12. No adverse
      event was observed in both groups. CONCLUSION: In elder patients with asthma,
      treatment with BUD/FM does not have any clinical disadvantage and may provide
      better efficacy in lung function, QOL, and possibly anti-inflammation compared
      with BUD plus Tulo treatment.

PMID- 22868524
TI  - Atrial fibrillation detection using an iPhone 4S.
AB  - Atrial fibrillation (AF) affects three to five million Americans and is
      associated with significant morbidity and mortality. Existing methods to diagnose
      this paroxysmal arrhythmia are cumbersome and/or expensive. We hypothesized that
      an iPhone 4S can be used to detect AF based on its ability to record a pulsatile
      photoplethysmogram signal from a fingertip using the built-in camera lens. To
      investigate the capability of the iPhone 4S for AF detection, we first used two
      databases, the MIT-BIH AF and normal sinus rhythm (NSR) to derive discriminatory
      threshold values between two rhythms. Both databases include RR time series
      originating from 250 Hz sampled ECG recordings. We rescaled the RR time series to
      30 Hz so that the RR time series resolution is 1/30 (s) which is equivalent to
      the resolution from an iPhone 4S. We investigated three statistical methods
      consisting of the root mean square of successive differences (RMSSD), the Shannon
      entropy (ShE) and the sample entropy (SampE), which have been proved to be useful
      tools for AF assessment. Using 64-beat segments from the MIT-BIH databases, we
      found the beat-to-beat accuracy value of 0.9405, 0.9300, and 0.9614 for RMSSD,
      ShE, and SampE, respectively. Using an iPhone 4S, we collected 2-min pulsatile
      time series from 25 prospectively recruited subjects with AF pre- and
      postelectrical cardioversion. Using derived threshold values of RMSSD, ShE and
      SampE from the MIT-BIH databases, we found the beat-to-beat accuracy of 0.9844,
      0.8494, and 0.9522, respectively. It should be recognized that for clinical
      applications, the most relevant objective is to detect the presence of AF in the
      data. Using this criterion, we achieved an accuracy of 100% for both the MIT-BIH
      AF and iPhone 4S databases.

PMID- 22868525
TI  - Multiscale entropy study of medical laser speckle contrast images.
AB  - Laser speckle contrast imaging (LSCI) is a noninvasive full-field optical imaging
      technique that gives a 2-D microcirculatory blood flow map of tissue. Due to
      novelty of commercial laser speckle contrast imagers, image processing of LSCI
      data is new. By opposition, the numerous signal processing works of laser Doppler
      flowmetry (LDF) data-that give a 1-D view of microvascular blood flow-have led to
      interesting physiological information. Recently, analysis of multiscale entropy
      (MSE) of LDF signals has been proposed. A nonmonotonic evolution of MSE with two
      distinctive scales-probably dominated by the cardiac activity-has been reported.
      We herein analyze MSE of LSCI data. We compare LSCI results with the ones of LDF
      signals obtained during the same experiment. We show that when time evolution of
      LSCI single pixels is studied, MSE presents a monotonic decreasing pattern,
      similar to the one of Gaussian white noises. By opposition, when the mean of LSCI
      pixel values is computed in a region of interest (ROI) and followed with time,
      MSE pattern becomes close to the one of LDF data, for ROI large enough. LSCI is
      gaining increased interest for blood flow monitoring. The physiological
      implications of our results require future study.

PMID- 22868526
TI  - A decentralized modular control framework for robust control of FES-activated
      walker-assisted paraplegic walking using terminal sliding mode and fuzzy logic
      control.
AB  - A major challenge to developing functional electrical stimulation (FES) systems
      for paraplegic walking and widespread acceptance of these systems is the design
      of a robust control strategy that provides satisfactory tracking performance. The
      systems need to be robust against time-varying properties of neuromusculoskeletal
      dynamics, day-to-day variations, subject-to-subject variations, external
      disturbances, and must be easily applied without requiring offline identification
      during different experimental sessions. Another major problem related to walker
      assisted FES-activated walking concerns the high metabolic rate and upper body
      effort that limit the clinical applications of FES systems. In this paper, we
      present a novel decentralized modular control framework for robust control of
      walker-assisted FES-activated walking. For each muscle-joint dynamics, an
      independent module control is designed, and the dynamics of the plant are
      identified online. This process requires no prior knowledge about the dynamics of
      the plant to be controlled and no offline learning phase. The module is based on
      adaptive fuzzy terminal sliding mode control and fuzzy logic control. The module
      control adjusts both pulse-amplitude and pulsewidth of the stimulation signal in
      such a way that upper body effort is minimized and the lower extremity walking
      pattern lies within a defined boundary of the reference trajectory. The proposed
      control strategy has been evaluated on three paraplegic subjects. The results
      showed that accurate tracking performance and smooth walking pattern were
      achieved. This favorable performance was obtained without requiring offline
      identification, manual adjustments, and predefined ON/OFF timing of the muscles.

PMID- 22868527
TI  - Detection of cortical slow waves in the sleep EEG using a modified matching
      pursuit method with a restricted dictionary.
AB  - In this paper, an innovative knowledge-based methodological framework to detect
      sleep slow waves (SSW) in the human sleep electroencephalogram (EEG) is proposed.
      Based on a restricted matching pursuit (RMP) algorithm, automatic pattern
      recognition of SSW is implemented using a small dictionary of Gabor functions
      modeling the target waveform morphological characteristics. The method describes
      EEG signals in terms of SSW properties and provides detection thresholds based on
      the largest MP coefficients. A computer software implementation of this new
      method was tested on a database of overnight polysomnographic recordings
      collected in 15 young healthy subjects and visually scored by a trained sleep
      expert. In addition to full automation and fast application, the results obtained
      from the RMP algorithm, and evaluated using a rigorous performance evaluation
      metrics, showed excellent agreement as compared with expert scoring, with 97% of
      correct detections and a concordance of 67% in SSW time position and duration.
      The performances demonstrated by this new method were superior to that of a
      canonical detection algorithm introduced earlier, with an equivalent sensitivity
      but a significant 12% increase in precision (  p = 0.0002). By mimicking the way
      human processes information while scoring SSW, the RMP algorithm proves stable
      over time and sleep/wake states, and may thus be used with virtually no human
      intervention.

PMID- 22868528
TI  - Cross-scale coefficient selection for volumetric medical image fusion.
AB  - Joint analysis of medical data collected from different imaging modalities has
      become a common clinical practice. Therefore, image fusion techniques, which
      provide an efficient way of combining and enhancing information, have drawn
      increasing attention from the medical community. In this paper, we propose a
      novel cross-scale fusion rule for multiscale-decomposition-based fusion of
      volumetric medical images taking into account both intrascale and interscale
      consistencies. An optimal set of coefficients from the multiscale representations
      of the source images is determined by effective exploitation of neighborhood
      information. An efficient color fusion scheme is also proposed. Experiments
      demonstrate that our fusion rule generates better results than existing rules.

PMID- 22868529
TI  - Cuffless differential blood pressure estimation using smart phones.
AB  - Smart phones today have become increasingly popular with the general public for
      their diverse functionalities such as navigation, social networking, and
      multimedia facilities. These phones are equipped with high-end processors, high
      resolution cameras, and built-in sensors such as accelerometer, orientation
      sensor, and light-sensor. According to comScore survey, 26.2% of U.S. adults use
      smart phones in their daily lives. Motivated by this statistic and the diverse
      capability of smart phones, we focus on utilizing them for biomedical
      applications. We present a new application of the smart phone with its built-in
      camera and microphone replacing the traditional stethoscope and cuff-based
      measurement technique, to quantify vital signs such as heart rate and blood
      pressure. We propose two differential blood pressure estimating techniques using
      the heartbeat and pulse data. The first method uses two smart phones whereas the
      second method replaces one of the phones with a customized external microphone.
      We estimate the systolic and diastolic pressure in the two techniques by
      computing the pulse pressure and the stroke volume from the data recorded. By
      comparing the estimated blood pressure values with those measured using a
      commercial blood pressure meter, we obtained encouraging results of 95-100%
      accuracy.

PMID- 22868530
TI  - Papillary glioneuronal tumor--a rare entity: report of four cases and brief
      review of literature.
AB  - PURPOSE: Papillary glioneuronal tumors (PGNT) have been recently included as a
      distinct entity in the WHO classification of tumors of the central nervous
      system. Their molecular pathogenesis is not clear. In the current study, we
      present the morphological, immunohistochemical, and molecular features of four
      cases of PGNT reported over the past 11 years. METHODS: Over a period of 11 years
      (January 2000-February 2010), there were four cases of PGNT, which were reviewed
      for histomorphological features. TP53 and IDH1 mutations were assessed using
      antibodies against p53 protein and for mutant IDH1(R132H) protein, respectively.
      Immunohistochemistry was also performed for epidermal growth factor receptor
      (EGFR) protein. Fluorescence in situ hybridization assay was used for analyzing
      1p/19q deletion status. RESULTS: All the tumors showed the characteristic
      biphasic morphology. Rare findings included minigemistocyte-like cells in one,
      angiomatous areas in three, focal necrosis in one, and a high MIB-1 labeling
      index of 12 and 13 %, respectively, in two of the cases. All lacked EGFR, IDH1
      expression, and 1p/19q deletions. Interestingly, antibody for p53 labeled the
      tumor cells, mainly those showing glial differentiation, in two cases. At a mean
      follow-up of 30 months, there was no evidence of disease progression except in
      one case which recurred after 24 months. CONCLUSION: PGNT are rare CNS neoplasms.
      Despite showing focal morphological features reminiscent of oligodendroglial
      tumors and presence of astrocytic component, they usually lack the common genetic
      alterations involved in the pathogenesis of gliomas. Multi-institutional pooling
      of cases may aid in elucidating their oncogenetic pathway.

PMID- 22868532
TI  - Comment on: Surgical revascularization for childhood moyamoya, Child's Nerv Syst
      28: 1041-1048, 2012.

PMID- 22868533
TI  - Surgical management of intractable chyluria: a comparison of retroperitoneoscopy
      with open surgery.
AB  - BACKGROUND: Retroperitoneoscopic renal pedicle lymphatic disconnection has been
      described in the management of intractable chyluria. METHODS: We retrospectively
      reviewed the clinical outcomes of 76 patients with intractable chyluria
      undergoing renal pedicle lymphatic disconnection via a retroperitoneoscopic (n =
      59) or conventional open approach (n = 17). Operative time, intraoperative blood
      loss, volume of postoperative drainage, postoperative draining time,
      postoperative intestinal recovery, intraoperative and postoperative
      complications, and postoperative hospital stay were evaluated. RESULTS: Compared
      with open surgery, retroperitoneoscopy was superior in terms of operative time,
      intraoperative blood loss, postoperative drainage, postoperative draining time,
      postoperative intestinal recovery time, and postoperative hospital stay.
      Recurrence developed in 2 patients due to the contralateral chylous efflux
      confirmed by cystoscopy during the period of 9-85 months of follow-up.
      CONCLUSIONS: With minimal invasion, sparing operative time, less blood loss, and
      rapid recovery, retroperitoneoscopic renal pedicle lymphatic disconnection can
      achieve at least the same clinical efficacy as open surgery.

PMID- 22868531
TI  - Risk and protective factors of intraventricular hemorrhage in preterm babies in
      Wuhan, China.
AB  - OBJECTIVE: The aim of this study is to identify prenatal and perinatal risk and
      protective factors for the development of IVH, using a retrospective and case
      control clinical study. METHODS: Prenatal and perinatal data were collected from
      three NICUs between January 2010 and December 2010. Univariate analysis was
      performed between case and control groups, and multivariate analysis was done to
      find out risk and protective factors for development of IVH. Further analysis of
      these variables was undertaken for gestational age strata <30, 30-34, and 35-37
      weeks. RESULTS: By univariate analysis, factors related with IVH were C-section,
      prenatal steroid, pregnancy-induced hypertension, transport from other hospital,
      hypothermia, Apgar score at 1 and 5 min < 4, luminal, pathological jaundice, RDS,
      hypotension, volume expansion/inotropics, PO(2), repeat suctioning, and
      mechanical ventilation (P < 0.05). Five variables remained significant in
      multivariate analysis. C-section and prenatal steroid use were protective
      variables while mechanical ventilation, hypotension, and transport from other
      hospital were risk factors. Further analysis of these variables was undertaken
      for gestational age strata <30, 30-34, and 35-37 weeks. Prenatal steroid use
      remained significant as a protective variable in gestational age less than 35
      weeks; hypotension was shown to be a risk factor just in the time period between
      30-34 weeks; transport from other hospital was a risk factor in gestational age
      more than 30 weeks; mechanical ventilation remained non-significant during the
      gestational age strata studied. CONCLUSION: In the present study, factors that
      related to neonatal IVH included hypotension, prenatal steroid use, and
      transportation.

PMID- 22868538
TI  - The conundrum of "tension type headache".

PMID- 22868539
TI  - Migraine diagnosis and pathophysiology.
AB  - PURPOSE OF REVIEW: This article describes current knowledge regarding headache,
      especially migraine, and includes information on genetics, anatomy,
      pathophysiology, and pharmacology in order to demonstrate their relevance to
      clinical phenomenology. RECENT FINDINGS: Animal models show that drugs effective
      in migraine prevention may work by raising the threshold for initiating cortical
      spreading depression and may also attenuate the response to simulation. SUMMARY:
      Great advances have been made in diagnosing and understanding migraine over the
      past several decades. Tools such as the International Classification of Headache
      Disorders assist in making diagnoses. Although blood vessel changes do occur in
      migraine, they are not timelocked to the occurrence of head pain. Cortical
      spreading depression is at least one trigger for the events that occur in
      migraine. Migraine may be due to the interplay of host susceptibility and various
      triggers. Nitric oxide and calcitonin gene-related peptide are important
      mediators, and estrogen seems to "ramp up" the system.

PMID- 22868540
TI  - Acute and preventive treatment of migraine.
AB  - PURPOSE OF REVIEW: Migraine remains underdiagnosed and undertreated despite
      advances in the understanding of its pathophysiology and management. This article
      focuses on acute and preventive treatment of migraine, including the mechanisms
      of action, dosing and side effects of medications, and strategies for the most
      effective care. RECENT FINDINGS: Best practice suggests that acute migraine
      treatment should be stratified based on the severity of the individual event,
      with a goal of returning the patient to full function within 2 hours of
      treatment. Migraine prevention strategies continue to be underused in the United
      States. More than 1 in 4 patients with migraines may be candidates for preventive
      therapy. To obtain the best results from preventive therapy, slow titration to an
      adequate dose for an adequate timeframe with good documentation of the results is
      recommended. SUMMARY: This article reviews several options for managing acute
      attacks, including information on expected efficacy, dosing, and adverse effects.
      Strategies for effective application of acute therapies are discussed. Prevention
      can be added to acute therapy depending on headache characteristics such as
      frequency, severity, disability, and the presence of comorbid conditions. The
      mechanisms of action of preventive medications and strategies for their most
      effective use are discussed.

PMID- 22868541
TI  - Secondary headaches.
AB  - PURPOSE OF REVIEW: This article identifies the pertinent historical issues that
      lead to the identification of those headaches needing additional testing to
      exclude a serious underlying cause. RECENT FINDINGS: Recurrences of giant cell
      arteritis, even after presumed successful treatment, are common. Postural
      orthostatic tachycardia syndrome is an often unrecognized cause of headache.
      SUMMARY: Patients with a primary headache disorder are more susceptible to the
      development of headache when a secondary cause occurs. Their headaches may be
      phenotypically similar to their primary headache disorder. Therefore, a secondary
      cause should be considered in patients with preexisting headache disorders who
      develop a significant increase in the number and severity of those attacks.

PMID- 22868542
TI  - Nonmedication, alternative, and complementary treatments for migraine.
AB  - PURPOSE OF REVIEW: The efficacy of some nonpharmacologic therapies appears to
      approach that of most drugs used for the prevention of migraine and tension-type
      headaches. These therapies often carry a very low risk of serious side effects
      and frequently are much less expensive than pharmacologic therapies. Considering
      this combination of efficacy, minimal side effects, and cost savings, medications
      should generally not be prescribed alone but rather in combination with
      nonpharmacologic therapies. RECENT FINDINGS: In addition to the established
      nonpharmacologic therapies, such as biofeedback, relaxation training, butterbur,
      riboflavin, magnesium, and coenzyme Q10 (CoQ10) supplementation, recent data
      provide support for the use of aerobic exercise and acupuncture. Discovery of the
      high incidence of the C677T mutation of the methylenetetrahydrofolate reductase
      gene, MTHFR, and attendant elevation of homocysteine levels in patients with
      migraine with aura led to a trial of cyanocobalamin, folate, and pyridoxine in
      these patients. This trial showed that taking these three supplements resulted in
      a reduction of homocysteine levels and improvement of migraines. SUMMARY:
      Therapies proven (to various degrees) to be effective for migraine include
      aerobic exercise; biofeedback; other forms of relaxation training; cognitive
      therapies; acupuncture; and supplementation with magnesium, CoQ10, riboflavin,
      butterbur, feverfew, and cyanocobalamin with folate and pyridoxine.

PMID- 22868543
TI  - Medication-overuse headache.
AB  - PURPOSE OF REVIEW: Medication-overuse headache (MOH) is a chronic daily headache
      in which acute medications used at high frequency cause transformation to
      headache occurring 15 or more days per month for 4 or more hours per day if left
      untreated. MOH is a form of US Food and Drug Administration-defined chronic
      migraine. This review will describe (1) MOH clinical features and diagnosis, (2)
      pathophysiology and structural and functional MOH brain changes, and (3)
      prevention and treatment of MOH. RECENT FINDINGS: MOH causes structural and
      functional brain changes. Any butalbital or opioid use increases the risk of
      transforming episodic into chronic migraine (sometimes referred to as
      chronification). The American Migraine Prevalence and Prevention Study
      demonstrated that transformation is most likely to occur with 5 days of
      butalbital use per month, 8 days of opioid use per month, 10 days of triptan or
      combination analgesic use per month, and 10 to 15 days of nonsteroidal anti
      inflammatory use per month. Acute migraine treatment should be limited to 2 or
      fewer days per week, and opioids and butalbital should be avoided.Treatment of
      MOH consists of combining prophylaxis, 100% wean of overused acute medications,
      and provision of new acute medications, strictly limiting use to 2 or fewer days
      per week. Wean can be done slowly in an outpatient setting or it can be done
      abruptly, sometimes requiring hospitalization with medicine bridges. SUMMARY: MOH
      development is linked to baseline frequency of headache days per month, acute
      medication class ingested, frequency of acute medications ingested, and other
      risk factors. Using less effective or nonspecific medication for severe migraine
      results in inadequate treatment response, with redosing and attack prolongation,
      frequently leading to chronification. Use of any barbiturates or opioids
      increases the transformation likelihood.Patients with MOH can usually be
      effectively treated. The first step is 100% wean, followed by establishing
      preventive medications such as onabotulinumtoxinA or daily prophylaxis and
      providing acute treatment for severe migraine 2 or fewer days per week. Slow wean
      or quick termination of rebound medications can be accomplished for most patients
      on an outpatient basis, but some more difficult problems may need referral for
      multidisciplinary day hospital or inpatient treatments.

PMID- 22868544
TI  - Tension-type headache.
AB  - PURPOSE OF REVIEW: This article provides an update on the appropriate diagnosis
      and evaluation of patients with tension-type headache, with reviews of the latest
      concepts regarding pathogenesis and the evidence-based recommendations for
      management of this disorder. RECENT FINDINGS: Pericranial myofascial mechanisms
      are probably of importance in episodic tension-type headache, whereas
      sensitization of central nociceptive pathways and inadequate endogenous
      antinociceptive circuitry seem to be more relevant in chronic tension-type
      headache. While acute treatment with simple analgesics is generally helpful,
      recent data attempting to document the efficacy of preventive therapies are
      unconvincing. SUMMARY: Tension-type headache is the most common form of headache
      in the general population. It is characterized by recurrent episodes of headache
      that are relatively featureless and mild to moderate in intensity. The diagnosis
      is based solely on the history and examination. Exclusion of secondary headaches
      or forms of migraine is important in the assessment process. Despite extensive
      investigation, the underlying pathophysiology remains a matter of speculation,
      with peripheral muscular and CNS components both likely involved. Acute
      management with simple analgesics, nonsteroidal anti-inflammatory drugs, and
      caffeine-containing compounds is typically effective. Preventive therapies
      include a number of nonpharmacologic recommendations as well as several
      antidepressant drugs. Prognosis is generally favorable.

PMID- 22868545
TI  - Migraine in women.
AB  - PURPOSE OF REVIEW: This article discusses hormonal milestones and the influence
      that hormonal fluctuations make in the frequency and severity of migraine in
      women and includes information on acute, short-term, and preventive strategies
      for hormonally influenced migraine and the situations in which hormonal therapies
      may be offered. RECENT FINDINGS: Genomic patterns in adolescent girls
      differentiate between menstrually related migraine and non-menstrually related
      migraine. The age at initiation of estrogen replacement therapy appears to be
      significant with respect to stroke. No increase in stroke occurred in women on
      low-dose (50 ug or less) transdermal estrogen replacement compared to women not
      using estrogen replacement. Childhood maltreatment is more common in women with
      migraine and depression than in women with migraine alone. SUMMARY: Management of
      hormonally influenced migraine involves a clear identification of the
      relationship between migraine and hormone change. A thorough history and detailed
      diary are critical in identifying this relationship and in predicting response or
      following response to hormonal therapies. The evolution of migraine in an
      individual may be strongly driven by hormonal shifts. Although limited, clinical
      evidence suggests that oral contraceptive use in young women with episodic
      migraine may transform their pattern into chronic migraine. Thus, particular
      attention to changes in migraine patterns following either endogenous or
      exogenous hormonal changes is crucial. Providing reassurance and education that
      migraine is a biological disorder and providing an understanding of the role of
      estrogen in the frequency and severity of migraine can guide treatment choices.
      Pharmacologic treatments include acute therapy, with short-term and standard
      prevention offered where appropriate. Hormonal therapies are not first-line
      therapies but may be important choices for a woman with migraine whose estrogen
      fluctuation is continually exacerbating migraine attacks. Given the many hormonal
      stages during the life of a woman with migraine, therapies may vary according to
      hormonal stage and status. Overall wellness should also be emphasized; regular
      exercise, balanced diet, smoking cessation, weight control, and sleep hygiene are
      important in the management of migraine.

PMID- 22868546
TI  - Headaches in children.
AB  - PURPOSE OF REVIEW: This article provides an overview of the differences in
      epidemiology, presentation, and treatment of pediatric headache compared to adult
      headache. NEW FINDINGS: New proposals are presented regarding the classification
      of pediatric migraine and ophthalmoplegic migraine. The distinction between
      basilar migraine and migraine with aura is reconsidered. SUMMARY: Pediatric
      headache is a common but underdiagnosed condition. Primary headache syndromes, in
      particular migraine, can present differently in children than in adults.
      Diagnosis can be problematic, especially in young children, because standard
      criteria used for classification are often incomplete. Treatment focuses on
      biobehavioral modification and adapted use of standard adult medication
      management.

PMID- 22868547
TI  - Facial pain, cervical pain, and headache.
AB  - PURPOSE OF REVIEW: This review discusses the role of musculoskeletal structures
      of the jaw and neck in perpetuating or triggering primary headache. Because
      treatments aimed at these structures often reduce headache, a better
      understanding of their role in headache is needed. RECENT FINDINGS: Central
      sensitization may result in changes in the afferent pathways, making
      communication from cervical and temporomandibular nociceptive neurons to the
      trigeminal nucleus possible. This provides the pathophysiologic basis for
      directing therapy to the neck or temporomandibular joint to alleviate primary
      headache. SUMMARY: Clinicians should recognize the significant role that
      musculoskeletal structures of the head and neck play in the perpetuation of
      headache and the importance of evaluating every patient for temporomandibular
      disorders and cervical abnormalities.

PMID- 22868548
TI  - Trigeminal autonomic cephalalgias.
AB  - PURPOSE OF REVIEW: This article covers the clinical manifestations and
      differential diagnosis of the trigeminal autonomic cephalalgias (TACs). RECENT
      FINDINGS: TACs comprise a subgroup of primary headache disorders presenting with
      lateralized, often severe, pain accompanied by cranial autonomic features. The
      key syndromes are cluster headache, paroxysmal hemicrania, short-lasting
      unilateral neuralgiform headache attacks with conjunctival injection and tearing
      (SUNCT)/short-lasting unilateral neuralgiform headache attacks with cranial
      autonomic features (SUNA), and hemicrania continua. Lateralization of symptoms
      and signs is the key feature differentiating the TACs and migraine. When
      diagnosing a TAC, it is appropriate to consider underlying pituitary or pituitary
      region pathology. Cluster headache responds to oxygen and parenteral triptans,
      with verapamil having the most success for prevention. Paroxysmal hemicrania
      responds to indomethacin. SUNCT/SUNA responds to lamotrigine and topiramate.
      Hemicrania continua responds to indomethacin. SUMMARY: TACs are a unique group of
      primary headache syndromes with individual features and specific responses to
      treatment that make their identification crucial for optimum management.

PMID- 22868549
TI  - Treatment of refractory headache: potential conflicts of interest in coding.
AB  - Issues directly or indirectly related to the increasing costs of health care
      services have the potential to adversely affect physicians' fiduciary
      responsibilities to their patients. Coding deception in response to perceived
      unfairness in reimbursement practices represents one of these potential adverse
      influences. This case discussion addresses the potential motivations underlying
      coding deception and the reasons it cannot be supported from either a legal or
      ethical perspective.

PMID- 22868550
TI  - Migraine and disability rights.
AB  - Patients with migraine often have substantial disabilities. US federal law
      provides protections for disabled Americans. This discussion provides information
      regarding the disability rights of patients with transformed migraine.

PMID- 22868551
TI  - Coding for headache.

PMID- 22868557
TI  - Multiple-choice questions.

PMID- 22868559
TI  - Patient management problem.

PMID- 22868562
TI  - Eigenspace based minimum variance beamforming applied to ultrasound imaging of
      acoustically hard tissues.
AB  - Minimum variance (MV) based beamforming techniques have been successfully applied
      to medical ultrasound imaging. These adaptive methods offer higher lateral
      resolution, lower sidelobes, and better definition of edges compared to delay and
      sum beamforming (DAS). In standard medical ultrasound, the bone surface is often
      visualized poorly, and the boundaries region appears unclear. This may happen due
      to fundamental limitations of the DAS beamformer, and different artifacts due to,
      e.g., specular reflection, and shadowing. The latter can degrade the robustness
      of the MV beamformers as the statistics across the imaging aperture is violated
      because of the obstruction of the imaging beams. In this study, we employ
      forward/backward averaging to improve the robustness of the MV beamforming
      techniques. Further, we use an eigen-spaced minimum variance technique (ESMV) to
      enhance the edge detection of hard tissues. In simulation, in vitro, and in vivo
      studies, we show that performance of the ESMV beamformer depends on estimation of
      the signal subspace rank. The lower ranks of the signal subspace can enhance
      edges and reduce noise in ultrasound images but the speckle pattern can be
      distorted.

PMID- 22868563
TI  - The ACTN3 XX genotype's underrepresentation in Japanese elite wrestlers.
AB  - PURPOSE: To examine the relationship between ACTN3 polymorphisms and level of
      athletic performance in Japanese wrestlers. METHODS: The control group consisted
      of 243 healthy Japanese individuals. The authors divided 135 wrestlers into 3
      groups based on their results in national or international competitions. They
      classified as elite 24 wrestlers who had placed in the top 8 in a world
      championship or participated in Olympic games, 28 wrestlers who had participated
      in world championships or become champions in Japan's national championships were
      classified as subelite, and 83 wrestlers were classified as national (N-W, ie,
      national-level wrestler). In addition, the authors combined the elite and
      subelite to form the classification international-level wrestlers (I-W). RESULTS:
      The frequency of the null X allele and the XX genotype were significantly lower
      in the I-W group than in the control group. However, there was no significant
      difference in ACTN3 genotype or allele frequency between the N-W and control
      groups. The frequency of the ACTN3 XX genotype in the elite groups was lower than
      that of all groups, and a linear tendency was observed between ACTN3 XX genotype
      and athletic status. CONCLUSIONS: In conclusion, the data indicated that ACTN3
      polymorphisms were related to athletic performance in Japanese wrestlers.

PMID- 22868564
TI  - The Veterans Affairs National Quality Scholars program: a model for
      interprofessional education in quality and safety.
AB  - The Quality and Safety Education for Nurses (QSEN) project is enhancing the
      emphasis on quality care and patient safety content in nursing schools. A
      partnership between QSEN and the Veterans Affairs National Quality Scholars
      program resulted in a unique experiential, interdisciplinary fellowship for both
      nurses and physicians. This article introduces the Veterans Affairs National
      Quality Scholars program and provides examples of learning activities and
      fellows' accomplishments. Interprofessional quality and safety education at the
      doctoral and postdoctoral levels is germane to improving the quality of health
      care.

PMID- 22868565
TI  - Quality nursing care and opportunities for improvement: insights from patients
      and family members.
AB  - A study was undertaken to delineate patients' and families' experiences and
      perceptions associated with their nurse-patient therapeutic relationships and
      nursing care. Data were analyzed using a directed content analysis approach. Two
      key themes emerged: patients and family members described primarily receiving
      excellent nursing care and to a lesser extent substandard care. Study findings
      have implications for nurse leaders to enhance nurses' therapeutic relationships
      with patients and family members and patient-centered care within their
      organizations.

PMID- 22868566
TI  - Effect of Magnet hospital recognition on 2 patient outcomes.
AB  - The purpose of this study was to explore whether Magnet hospitals had better
      nursing-sensitive outcomes than non-Magnet hospitals. Eighty Magnet hospitals
      were identified in the Agency for Healthcare Research and Quality Healthcare Cost
      and Utilization Project databases and matched with 80 non-Magnet hospitals on 12
      hospital characteristics. Comparative analysis demonstrated no significant
      differences for risk-adjusted rates for pressure ulcers and failure to rescue.
      Future investigation should examine what clinical benefits might exist that
      distinguish Magnet from non-Magnet hospitals.

PMID- 22868567
TI  - Ejectisins: tough and tiny polypeptides are a major component of cryptophycean
      ejectisomes.
AB  - Fragments of discharged ejectisomes were isolated from two Cryptomonas and a
      Chroomonas species by detergent treatment followed by Percoll density gradient
      centrifugation. The fragments withstand high concentrated detergent solutions,
      reducing agents and freeze-thawing. Disintegration was achieved in 6 M guanidine
      hydrochloride. Reassembly into long, filamentous, ejectisome-like structures
      occurred after dialysis. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis revealed that the polypeptide patterns of isolated ejectisome
      fragments and of reconstituted ejectisome-like structures were dominated by
      polypeptides with relative molecular weights of approximately 6 kDa. The
      polypeptides were not glycosylated and did not cross-react with antisera directed
      against recombinant Reb polypeptides which constitute the R-bodies of Caedibacter
      taeniospiralis. A polyclonal antiserum directed against reconstituted, ejectisome
      like filaments cross-reacted with the 6-kDa polypeptides and immunolabeled
      extruded ejectisome filaments. Twenty amino acid residues, obtained by N-terminal
      amino acid sequence analysis, matched to polypeptide sequences deduced from cDNA
      sequences of the cryptophyte Guillardia theta. The term "ejectisins" is
      introduced for the 6-kDa polypeptides which represent a major component of
      cryptophycean ejectisomes.

PMID- 22868568
TI  - Optimizing multiscale SSIM for compression via MLDS.
AB  - A crucial step in the assessment of an image compression method is the evaluation
      of the perceived quality of the compressed images. Typically, researchers ask
      observers to rate perceived image quality directly and use these rating measures,
      averaged across observers and images, to assess how image quality degrades with
      increasing compression. These ratings in turn are used to calibrate and compare
      image quality assessment algorithms intended to predict human perception of image
      degradation. There are several drawbacks to using such omnibus measures. First,
      the interpretation of the rating scale is subjective and may differ from one
      observer to the next. Second, it is easy to overlook compression artifacts that
      are only present in particular kinds of images. In this paper, we use a recently
      developed method for assessing perceived image quality, maximum likelihood
      difference scaling (MLDS), and use it to assess the performance of a widely-used
      image quality assessment algorithm, multiscale structural similarity (MS-SSIM).
      MLDS allows us to quantify supra-threshold perceptual differences between pairs
      of images and to examine how perceived image quality, estimated through MLDS,
      changes as the compression rate is increased. We apply the method to a wide range
      of images and also analyze results for specific images. This approach circumvents
      the limitations inherent in the use of rating methods, and allows us also to
      evaluate MS-SSIM for different classes of visual image. We show how the data
      collected by MLDS allow us to recalibrate MS-SSIM to improve its performance.

PMID- 22868569
TI  - Geometric flow approach for region-based image segmentation.
AB  - Geometric flows have been successfully used for surface modeling and designing,
      largely because they are inherently good at controlling geometric shape
      evolution. Variational image segmentation approaches, on the other hand, detect
      objects of interest by deforming certain given shapes. This motivates us to
      revisit the minimal partition problem for segmentation of images, and propose a
      new geometric flow-based formulation and solution to it. Our model intends to
      derive a mapping that will evolve given contours or piecewise-constant regions
      toward objects in the image. The mapping is approximated by B-spline basis
      functions, and the positions of the control points are to be determined. Starting
      with the energy functional based on intensity averaging, we derive a Euler
      Lagrange equation and then a geometric evolution equation. The linearized system
      of equations is efficiently solved via a special matrix-vector multiplication
      technique. Furthermore, we extend the piecewise-constant model to a piecewise
      smooth model which effectively handles images with intensity inhomogeneity.

PMID- 22868570
TI  - Nonlocal transform-domain filter for volumetric data denoising and
      reconstruction.
AB  - We present an extension of the BM3D filter to volumetric data. The proposed
      algorithm, BM4D, implements the grouping and collaborative filtering paradigm,
      where mutually similar d-dimensional patches are stacked together in a (d+1)
      dimensional array and jointly filtered in transform domain. While in BM3D the
      basic data patches are blocks of pixels, in BM4D we utilize cubes of voxels,
      which are stacked into a 4-D "group." The 4-D transform applied on the group
      simultaneously exploits the local correlation present among voxels in each cube
      and the nonlocal correlation between the corresponding voxels of different cubes.
      Thus, the spectrum of the group is highly sparse, leading to very effective
      separation of signal and noise through coefficient shrinkage. After inverse
      transformation, we obtain estimates of each grouped cube, which are then
      adaptively aggregated at their original locations. We evaluate the algorithm on
      denoising of volumetric data corrupted by Gaussian and Rician noise, as well as
      on reconstruction of volumetric phantom data with non-zero phase from noisy and
      incomplete Fourier-domain (k-space) measurements. Experimental results
      demonstrate the state-of-the-art denoising performance of BM4D, and its
      effectiveness when exploited as a regularizer in volumetric data reconstruction.

PMID- 22868571
TI  - Multiscale gradients-based color filter array interpolation.
AB  - Single sensor digital cameras use color filter arrays to capture a subset of the
      color data at each pixel coordinate. Demosaicing or color filter array (CFA)
      interpolation is the process of estimating the missing color samples to
      reconstruct a full color image. In this paper, we propose a demosaicing method
      that uses multiscale color gradients to adaptively combine color difference
      estimates from different directions. The proposed solution does not require any
      thresholds since it does not make any hard decisions, and it is noniterative.
      Although most suitable for the Bayer CFA pattern, the method can be extended to
      other mosaic patterns. To demonstrate this, we describe its application to the
      Lukac CFA pattern. Experimental results show that it outperforms other available
      demosaicing methods by a clear margin in terms of CPSNR and S-CIELAB measures for
      both mosaic patterns.

PMID- 22868572
TI  - Quantitative analysis of human-model agreement in visual saliency modeling: a
      comparative study.
AB  - Visual attention is a process that enables biological and machine vision systems
      to select the most relevant regions from a scene. Relevance is determined by two
      components: 1) top-down factors driven by task and 2) bottom-up factors that
      highlight image regions that are different from their surroundings. The latter
      are often referred to as "visual saliency." Modeling bottom-up visual saliency
      has been the subject of numerous research efforts during the past 20 years, with
      many successful applications in computer vision and robotics. Available models
      have been tested with different datasets (e.g., synthetic psychological search
      arrays, natural images or videos) using different evaluation scores (e.g., search
      slopes, comparison to human eye tracking) and parameter settings. This has made
      direct comparison of models difficult. Here, we perform an exhaustive comparison
      of 35 state-of-the-art saliency models over 54 challenging synthetic patterns,
      three natural image datasets, and two video datasets, using three evaluation
      scores. We find that although model rankings vary, some models consistently
      perform better. Analysis of datasets reveals that existing datasets are highly
      center-biased, which influences some of the evaluation scores. Computational
      complexity analysis shows that some models are very fast, yet yield competitive
      eye movement prediction accuracy. Different models often have common
      easy/difficult stimuli. Furthermore, several concerns in visual saliency
      modeling, eye movement datasets, and evaluation scores are discussed and insights
      for future work are provided. Our study allows one to assess the state-of-the
      art, helps to organizing this rapidly growing field, and sets a unified
      comparison framework for gauging future efforts, similar to the PASCAL VOC
      challenge in the object recognition and detection domains.

PMID- 22868573
TI  - Sampling optimization for printer characterization by direct search.
AB  - Printer characterization usually requires many printer inputs and corresponding
      color measurements of the printed outputs. In this brief, a sampling optimization
      for printer characterization on the basis of direct search is proposed to
      maintain high color accuracy with a reduction in the number of characterization
      samples required. The proposed method is able to match a given level of color
      accuracy requiring, on average, a characterization set cardinality which is
      almost one-fourth of that required by the uniform sampling, while the best method
      in the state of the art needs almost one-third. The number of characterization
      samples required can be further reduced if the proposed algorithm is coupled with
      a sequential optimization method that refines the sample values in the device
      independent color space. The proposed sampling optimization method is extended to
      deal with multiple substrates simultaneously, giving statistically better
      colorimetric accuracy (at the  alpha = 0.05 significance level) than sampling
      optimization techniques in the state of the art optimized for each individual
      substrate, thus allowing use of a single set of characterization samples for
      multiple substrates.

PMID- 22868574
TI  - Comparative proteomic profiles of Pinus monticola needles during early compatible
      and incompatible interactions with Cronartium ribicola.
AB  - The proteomic profiles of primary needles from Cr2-resistant and cr2-susceptible
      Pinus monticola seedlings were analysed post Cronartium ribicola inoculation by 2
      DE. One hundred-and-five protein spots exhibiting significant differential
      expression were identified using LC-MS/MS. Functional classification showed that
      the most numerous proteins are involved in defence signalling, oxidative burst,
      metabolic pathways, and other physiological processes. Our results revealed that
      differential expression of proteins in response to C. ribicola inoculation was
      genotype- and infection-stage dependent. Responsive proteins in resistant
      seedlings with incompatible white pine blister rust (WPBR) interaction included
      such well-characterized proteins as heat shock proteins (HSPs), reactive oxygen
      species (ROS) scavenging enzymes, and intermediate factors functioning in the
      signal transduction pathways triggered by well-known plant R genes, as well as
      new candidates in plant defence like sugar epimerase, GTP-binding proteins, and
      chloroplastic ribonucleoproteins. Fewer proteins were regulated in susceptible
      seedlings; most of them were in common with resistant seedlings and related to
      photosynthesis among others. Quantitative RT-PCR analysis confirmed HSP- and ROS
      related genes played an important role in host defence in response to C. ribicola
      infection. To the best of our knowledge, this is the first comparative proteomics
      study on WPBR interactions at the early stages of host defence, which provides a
      reference proteomic profile for other five-needle pines as well as resistance
      candidates for further understanding of host resistance in the WPBR pathosystem.

PMID- 22868575
TI  - Promoter activity of polypyrimidine tract-binding protein genes of potato
      responds to environmental cues.
AB  - Polypyrimidine tract-binding (PTB) proteins are RNA-binding proteins that target
      specific RNAs for post-transcriptional processing by binding cytosine/uracil
      motifs. PTBs have established functions in a range of RNA processes including
      splicing, translation, stability and long-distance transport. Six PTB-like genes
      identified in potato have been grouped into two clades based on homology to other
      known plant PTBs. StPTB1 and StPTB6 are closely related to a PTB protein
      discovered in pumpkin, designated CmRBP50, and contain four canonical RNA
      recognition motifs. CmRBP50 is expressed in phloem tissues and functions as the
      core protein of a phloem-mobile RNA/protein complex. Sequence from the potato
      genome database was used to clone the upstream sequence of these two PTB genes
      and analyzed to identify conserved cis-elements. The promoter of StPTB6 was
      enriched for regulatory elements for light and sucrose induction and defense.
      Upstream sequence of both PTB genes was fused to beta-glucuronidase and monitored
      in transgenic potato lines. In whole plants, the StPTB1 promoter was most active
      in leaf veins and petioles, whereas StPTB6 was most active in leaf mesophyll.
      Both genes are active in new tubers and tuber sprouts. StPTB6 expression was
      induced in stems and stolon sections in response to sucrose and in leaves or
      petioles in response to light, heat, drought and mechanical wounding. These
      results show that CmRBP50-like genes of potato exhibit distinct expression
      patterns and respond to both developmental and environmental cues.

PMID- 22868576
TI  - Quantitative genetic analysis and mapping of leaf angle in durum wheat.
AB  - The leaf erectness profile has been used to optimize plant architecture since
      erect leaves can enhance photosynthesis and dry matter production by greater
      sunlight capture. Brassinosteroid is a recent class of phytohormones that has
      been related to a more erect profile. There are no reports in the literature of
      the genetic variability of leaf angle in doubled haploid durum wheat populations;
      most studies on leaf angle have focused on the inheritance. Our aim was to study
      the genetic variation in flag and penultimate leaf angle in a durum wheat doubled
      haploid mapping population, identifying and mapping quantitative trait loci
      influencing leaf angle. An F(1)-derived doubled haploid population of 89 lines
      from the cross Strongfield/Blackbird was used to construct a genetic map using
      423 molecular marker loci. Two greenhouse experiments and one field test were
      conducted using an alpha lattice in a randomized complete block design with three
      replicates. The leaf angle was measured on flag and penultimate leaf with a
      protractor at three different growth stages. The results indicated poor to
      moderate correlations between the position of the leaf angle and the growth
      stage. Transgressive segregation beyond Strongfield and Blackbird of leaf angle
      was observed for all environments. Putative trait loci were identified on
      chromosomes 2A, 2B, 3A, 3B, 4B, 5B and 7A. This work helps to understand the
      genetics of leaf angle in durum wheat.

PMID- 22868579
TI  - Prescribing for children at the interfaces of care.
AB  - Prescribing for children at the primary-secondary/tertiary care interface is more
      complex than that for adults. Children often need unlicensed medicines and there
      may be issues over who will prescribe such items. There may also be issues in
      obtaining unlicensed medicines (specials) from community pharmacists. This
      article reviews the current arrangements in England relating to prescribing for
      children at the interfaces of care and describes the following: prescribing
      responsibility, shared-care arrangements, medication continuity on admission and
      discharge from hospital, unlicensed medicines, continuing-care medication
      arrangements and highlights potential service changes to maintain access to
      medicines for children.

PMID- 22868578
TI  - Cerebral palsy: the whys and hows.
AB  - The descriptive term of cerebral palsy encompasses the largest group of childhood
      movement disorders. Severity and pattern of clinical involvement varies widely
      dependent on the area of the central nervous system compromised. A
      multidisciplinary team approach is vital for all the aspects of management to
      improve function and minimise disability. From a medical viewpoint, there are two
      pronged approaches. First a focus on developmental and clinical comorbidities
      such as communication, behaviour, epilepsy, feeding problems, gastro-oesophageal
      reflux and infections; and second on specifics of muscle tone, motor control and
      posture. With regards to the latter, there is an increasing number of available
      treatments including oral antispasticity and antidystonic medications, injectable
      botulinum toxin, multilevel orthopaedic and neurosurgical options and a variety
      of complementary and alternative therapies.

PMID- 22868580
TI  - A novel approach for subretinal implantation of ultrathin substrates containing
      stem cell-derived retinal pigment epithelium monolayer.
AB  - OBJECTIVE: To evaluate the feasibility of a new technique for the implantation of
      ultrathin substrates containing stem cell-derived retinal pigment epithelium
      (RPE) cells into the subretinal space of retina-degenerate Royal College of
      Surgeon (RCS) rats. METHODS: A platform device was used for the implantation of 4
      um-thick parylene substrates containing a monolayer of human embryonic stem cell
      derived RPE (hESC-RPE). Normal Copenhagen rats (n = 6) and RCS rats (n = 5) were
      used for the study. Spectral-domain optical coherence tomography (SD-OCT)
      scanning and histological examinations were performed to confirm placement
      location of the implant. hESC-RPE cells attached to the substrate before and
      after implantation were evaluated using standard cell counting techniques.
      RESULTS: SD-OCT scanning and histological examination revealed that the
      substrates were precisely placed in the rat's subretinal space. The hESC-RPE cell
      monolayer that covered the surface of the substrate was found to be intact after
      implantation. Cell counting data showed that less than 2% of cells were lost from
      the substrate due to the implantation procedure (preimplantation count 2,792 +/-
      74.09 cells versus postimplantation count 2,741 +/- 62.08 cells). Detailed
      microscopic examination suggested that the cell loss occurred mostly along the
      edges of the implant. CONCLUSION: With the help of this platform device, it is
      possible to implant ultrathin substrates containing an RPE monolayer into the
      rat's subretinal space. This technique can be a useful approach for stem cell
      based tissue bioengineering techniques in retinal transplantation research.

PMID- 22868581
TI  - Application of Zeeman graphite furnace atomic absorption spectrometry with high
      frequency modulation polarization for the direct determination of aluminum,
      beryllium, cadmium, chromium, mercury, manganese, nickel, lead, and thallium in
      human blood.
AB  - Determination of aluminum (Al), beryllium (Be), cadmium (Cd), chromium (Cr),
      mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and thallium (Tl)
      concentrations in human blood using high-frequency modulation polarization Zeeman
      graphite furnace atomic absorption spectrometry (GFAAS) was performed. No sample
      digestion was used in the current study. Blood samples were diluted with
      deionized water or 0.1 % (m/v) Triton X-100 solution for Tl. Dilution factors
      ranged from 1/5 per volume for Be and Tl to 1/20 per volume for Cd and Pb. For
      Tl, Cd, and Hg, noble metals (gold, platinum, rhodium, etc.) were applied as
      surface modifiers. To mitigate chloride interference, 2 % (m/v) solution of
      NH(4)NO(3) was used as matrix modifier for Tl and Ni assessment. The use of
      Pd(NO(3))(2) as oxidative modifier was necessary for blood Hg and Tl measurement.
      Validation of the methods was performed by analyzing two-level reference material
      Seronorm. The precision of the designed methods as relative SD was between 4 and
      12 % (middle of a dynamic range) depending on the element. For additional
      validation, spiked blood samples were analyzed. Limits of detection (LoDs,
      3sigma, n = 10) for undiluted blood samples were 2.0 MUg L(-1) for Al, 0.08 MUg
      L(-1) for Be, 0.10 MUg L(-1) for Cd, 2.2 MUg L(-1) for Cr, 7 MUg L(-1) for Hg,
      0.4 MUg L(-1) for Mn, 2.3 MUg L(-1) for Ni, 3.4 MUg L(-1) for Pb, and 0.5 MUg L(
      1) for Tl. The LoDs achieved allowed determination of Al, Cd, Cr, Mn, Ni, and Pb
      at both toxic and background levels. Be, Hg, and Tl could be reliably measured at
      toxic levels only. The methods developed are used for clinical diagnostics and
      biological monitoring of work-related exposure.

PMID- 22868582
TI  - Reliable Decentralized Control of Fuzzy Discrete-Event Systems and a Test
      Algorithm.
AB  - A framework for decentralized control of fuzzy discrete-event systems (FDESs) has
      been recently presented to guarantee the achievement of a given specification
      under the joint control of all local fuzzy supervisors. As a continuation, this
      paper addresses the reliable decentralized control of FDESs in face of possible
      failures of some local fuzzy supervisors. Roughly speaking, for an FDES equipped
      with n local fuzzy supervisors, a decentralized supervisor is called k-reliable
      (1 <= k <= n) provided that the control performance will not be degraded even
      when n - k local fuzzy supervisors fail. A necessary and sufficient condition for
      the existence of k-reliable decentralized supervisors of FDESs is proposed by
      introducing the notions of Muc-controllability and k-reliable coobservability of
      fuzzy language. In particular, a polynomial-time algorithm to test the k-reliable
      coobservability is developed by a constructive methodology, which indicates that
      the existence of k-reliable decentralized supervisors of FDESs can be checked
      with a polynomial complexity. 

PMID- 22868583
TI  - OligoIS: Scalable Instance Selection for Class-Imbalanced Data Sets.
AB  - In current research, an enormous amount of information is constantly being
      produced, which poses a challenge for data mining algorithms. Many of the
      problems in extremely active research areas, such as bioinformatics, security and
      intrusion detection, or text mining, share the following two features: large data
      sets and class-imbalanced distribution of samples. Although many methods have
      been proposed for dealing with class-imbalanced data sets, most of these methods
      are not scalable to the very large data sets common to those research fields. In
      this paper, we propose a new approach to dealing with the class-imbalance problem
      that is scalable to data sets with many millions of instances and hundreds of
      features. This proposal is based on the divide-and-conquer principle combined
      with application of the selection process to balanced subsets of the whole data
      set. This divide-and-conquer principle allows the execution of the algorithm in
      linear time. Furthermore, the proposed method is easy to implement using a
      parallel environment and can work without loading the whole data set into memory.
      Using 40 class-imbalanced medium-sized data sets, we will demonstrate our
      method's ability to improve the results of state-of-the-art instance selection
      methods for class-imbalanced data sets. Using three very large data sets, we will
      show the scalability of our proposal to millions of instances and hundreds of
      features. 

PMID- 22868584
TI  - An Adaptive Approach to Learning Optimal Neighborhood Kernels.
AB  - Learning an optimal kernel plays a pivotal role in kernel-based methods.
      Recently, an approach called optimal neighborhood kernel learning (ONKL) has been
      proposed, showing promising classification performance. It assumes that the
      optimal kernel will reside in the neighborhood of a "pre-specified" kernel.
      Nevertheless, how to specify such a kernel in a principled way remains unclear.
      To solve this issue, this paper treats the pre-specified kernel as an extra
      variable and jointly learns it with the optimal neighborhood kernel and the
      structure parameters of support vector machines. To avoid trivial solutions, we
      constrain the pre-specified kernel with a parameterized model. We first discuss
      the characteristics of our approach and in particular highlight its adaptivity.
      After that, two instantiations are demonstrated by modeling the pre-specified
      kernel as a common Gaussian radial basis function kernel and a linear combination
      of a set of base kernels in the way of multiple kernel learning (MKL),
      respectively. We show that the optimization in our approach is a min-max problem
      and can be efficiently solved by employing the extended level method and
      Nesterov's method. Also, we give the probabilistic interpretation for our
      approach and apply it to explain the existing kernel learning methods, providing
      another perspective for their commonness and differences. Comprehensive
      experimental results on 13 UCI data sets and another two real-world data sets
      show that via the joint learning process, our approach not only adaptively
      identifies the pre-specified kernel, but also achieves superior classification
      performance to the original ONKL and the related MKL algorithms. 

PMID- 22868585
TI  - Late-onset smokers: how many, and associations with health behaviours and
      socioeconomic status.
AB  - AIMS: Adolescence is considered a critical phase for smoking initiation, while
      smoking initiation in adulthood has received less attention. In the present
      study, we investigated smoking initiation in early adulthood, with an additional
      focus on how socioeconomic status (SES) relates to late-onset smoking. METHODS:
      The Norwegian Longitudinal Health Behaviour Study followed a representative
      sample of adolescents (n=530) from age 13 (7th grade) to age 30 (years 1990-2007)
      through 9 waves of data collection. Information was collected on the adolescents'
      gender, smoking, alcohol use, cannabis use, physical activity, and SES. Those
      reporting to be smokers at age 30, but not at age 18, were defined as "late-onset
      smokers". RESULTS: At age 30, 21% were daily smokers, of which 45% met our
      definition of late-onset smoking. Participants with a low SES had a higher odds
      ratio for late-onset smoking (OR=3.42) and a lower odds ratio for quitting
      smoking (OR=0.40) after adjusting for confounders. CONCLUSIONS: Early adulthood
      is an additional critical phase for daily smoking initiation. The clear and
      consistent negative association between SES and late-onset smoking, as well as
      the positive association between SES and smoking cessation, contribute to the
      association between SES and smoking in the general adult population.

PMID- 22868586
TI  - Radiologic case study. Osteopetrosis.

PMID- 22868587
TI  - Orthopedics welcomes new associate editor.

PMID- 22868588
TI  - Femoral tunnel drilling from the anteromedial portal using the figure-4 position
      in ACL reconstruction.
AB  - Creation of the femoral tunnel in anterior cruciate ligament (ACL) reconstruction
      via the anteromedial portal can reproducibly achieve femoral tunnel positioning
      at the center of the femoral ACL footprint. Anteromedial portal drilling requires
      knee hyperflexion, which is awkward to perform. Knee hyperflexion to 120 degrees 
      can easily be achieved in the figure-4 position for femoral tunnel drilling via
      the anteromedial portal. The leg is hyperflexed in the figure-4 position on a
      Mayo stand. The offset femoral guide, guidewire, and drill are placed at the
      femoral ACL footprint via the anteromedial portal to create the femoral tunnel.

PMID- 22868589
TI  - Risk of disease transmission with bone allograft.

PMID- 22868590
TI  - Cloud-based preoperative planning for total hip arthroplasty: a study of
      accuracy, efficiency, and compliance.
AB  - As digital radiography becomes more prevalent, several systems for digital
      preoperative planning have become available. The purpose of this study was to
      evaluate the accuracy and efficiency of an inexpensive, cloud-based digital
      templating system, which is comparable with acetate templating. However, cloud
      based templating is substantially faster and more convenient than acetate
      templating or locally installed software. Although this is a practical solution
      for this particular medical application, regulatory changes are necessary before
      the tremendous advantages of cloud-based storage and computing can be realized in
      medical research and clinical practice.

PMID- 22868592
TI  - Perioperative management of antiplatelet agents.
AB  - Perioperative management of antiplatelet agents is a common challenge with the
      increased number of patients requiring long-term therapy following coronary
      stenting. Debate currently exists regarding if and when to discontinue
      antiplatelet therapy prior to elective surgery. The delicate balance between
      decreasing the risk of bleeding intraoperatively and minimizing the risk of stent
      thrombosis in patients who are already at a high thrombotic risk is a major
      concern. This article summarizes the information available for perioperative
      management of common antiplatelet agents, as well as antiplatelet agents in
      development.

PMID- 22868593
TI  - Tibial tubercle avulsion fractures in adolescent basketball players.
AB  - Tibial tubercle avulsion fractures most commonly occur in adolescent boys and
      usually result from pushing off or landing while jumping. These fractures are
      relatively uncommon but can have a significant functional effect. The purpose of
      this study was to determine the long-term outcome with return to play in 8
      adolescent basketball players with at least 4 years of postoperative
      reconditioning. Results with return to play at the preinjury level are favorable
      after treatment of acute tibial avulsion fractures in adolescent basketball
      players. Long-term outcome was excellent in all patients regardless of fracture
      type. Open reduction and internal fixation using 1 or 2 cancellous bone screws
      achieved union in all cases.

PMID- 22868595
TI  - Graft choice for a high-level athlete.

PMID- 22868596
TI  - Comparison of initial nonoperative and operative management of radial nerve palsy
      associated with acute humeral shaft fractures.
AB  - The optimal treatment approach for the initial management of radial nerve palsy
      associated with humeral shaft fractures has yet to be conclusively determined.
      The authors performed a systematic review of the literature to identify studies
      that compared the outcomes after initial nonoperative and operative management
      for radial nerve palsy associated with acute humeral shaft fractures. A meta
      analysis of the data from these studies was also performed to determine whether
      recovery from radial nerve palsy was more favorable in one approach compared with
      the other. The primary outcome was recovery from radial nerve palsy and the
      secondary outcome was complaints after treatment. Nine articles (1 prospective
      observational and 8 retrospective) were included in the meta-analyses. Operative
      management showed no improved recovery from radial nerve palsy compared with
      nonoperative management. Nonoperative management was associated with a decreased
      risk of complaints relative to operative management. Recovery from radial nerve
      palsy associated with acute humeral shaft fractures is not influenced by the
      initial management approach.

PMID- 22868597
TI  - Revision total hip arthroplasty in Jehovah's Witnesses.
AB  - Revision total hip arthroplasty (THA) is associated with greater blood loss than
      primary THA. Jehovah's Witnesses will not accept transfusions of blood or blood
      products and are thus at an increased risk for complications due to perioperative
      anemia. The purpose of this study was to report the clinical outcomes,
      radiographic outcomes, morbidity, and mortality of Jehovah's Witnesses who were
      medically optimized and underwent revision THA. Databases from 2 institutions
      were reviewed to identify 10 patients (11 THAs) who were Jehovah's Witnesses
      undergoing revision THA with a minimum 24-month follow-up. At most recent follow
      up, all patients were doing well clinically, with Harris Hip Scores greater than
      80 points. Radiographic evaluation demonstrated well-positioned components and no
      progressive radioluciencies. No major perioperative medical or surgical
      complications occurred in patients undergoing THA. Revision THA for aseptic
      causes results in good clinical outcomes in patients who are preoperatively
      optimized before undergoing surgery.

PMID- 22868598
TI  - Comparison of complications in single-incision minimally invasive THA and
      conventional THA.
AB  - The purpose of this meta-analysis was to investigate whether single-incision
      minimally invasive total hip arthroplasty (THA) is superior to conventional
      incision THA by comparing postoperative complication rates, Harris Hip Scores,
      and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores.
      Randomized, controlled trials comparing single-incision minimally invasive THA
      and conventional THA were reviewed. The methodological quality of each
      randomized, controlled trial was assessed using the Physiotherapy Evidence
      Database (PEDro) scale (Centre for Evidence-based Physiotherapy, The George
      Institute for Global Health, New South Wales, Australia). The Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach was used
      to determine the quality of the evidence. Fourteen studies involving 1254
      patients (1329 hips) were included in the meta-analysis, comprising 659 single
      incision minimally invasive THAs (mean patient age, 63.9 years) and 670
      conventional incision THAs (mean patient age, 65.0 years). A funnel plot of
      postoperative complication rates showed that a slight publication bias existed in
      the study. According to the meta-analysis, no significant statistical difference
      was observed in complication rates in no more than 3 postoperative years (odds
      ratio=1.06; 95% confidence interval, 0.69 to 1.63; P=.79), in Harris Hip Scores
      in no more than 2 postoperative years (weighted mean difference=0.71; 95%
      confidence interval, -3.09 to 4.51; P=.71), and in WOMAC scores at 6 weeks
      postoperatively (weighted mean difference=-0.55; 95% confidence interval, -3.54
      to 2.44; P=.72) between single-incision minimally invasive THA and conventional
      THA. Therefore, single-incision minimally invasive THA is not superior to
      conventional THA in early postoperative recovery, hip function, and complication
      rate.

PMID- 22868599
TI  - Postoperative flexion analysis of 3 rotating-platform knee designs.
AB  - Rotating-platform knee implants have successively undergone modifications to
      improve postoperative flexion. The cruciate-sacrificing Low Contact Stress (LCS)
      implant (DePuy Orthopaedics, Inc, Warsaw, Indiana) was modified into the cruciate
      substituting PFC Sigma RP (SigmaRP) implant and further into the PFC Sigma RPF
      (SigmaRPF) implant (DePuy Orthopaedics, Inc). The goal of this study was to
      determine whether these modifications improved postoperative flexion.
      Postoperative flexion at 2 years was compared against preoperative flexion with
      regard to the general demographics of each group.Statistical analysis showed that
      the pre- to postoperative flexion changes achieved by the SigmaRP (14.6 degrees )
      and the SigmaRPF (2.9 degrees ) were better (P<.001) than that achieved by the
      LCS (-10.3 degrees ); however, between the SigmaRP (14.6 degrees ) and the
      SigmaRPF (2.9 degrees ), the change was statistically insignificant (P=.045). In
      subgroups with preoperative flexion less than 125 degrees , postoperative flexion
      achieved was 100.1 degrees  with the LCS, 119.8 degrees  with the SigmaRP, and
      121.3 degrees  with the SigmaRPF. The difference between the SigmaRP and SigmaRPF
      and the LCS was statistically significant (P<.001), but between the SigmaRP and
      the SigmaRPF was statistically insignificant (P=.621). In subgroups with
      preoperative flexion 125 degrees  or more, postoperative flexion was 125 degrees 
      with the LCS, 132 degrees  with the SigmaRP, and 130 degrees  with the SigmaRPF,
      with no significant difference between groups (P=.416). Both cruciate
      substituting designs produced better postoperative flexion than the cruciate
      sacrificing design. The SigmaRP, despite less preoperative flexion (P=.004),
      achieved statistically better postoperative flexion than the LCS (P<.001). In
      subgroups with comparable preoperative flexion, no statistical difference in
      postoperative flexion was achieved by the SigmaRP and the SigmaRPF.

PMID- 22868600
TI  - Drilling the femoral tunnel during ACL reconstruction: transtibial versus
      anteromedial portal techniques.
AB  - Incorrect bone tunnel position, particularly on the femoral side, is a frequent
      cause of failed anterior cruciate ligament reconstruction. Several studies have
      reported that drilling the femoral tunnel through the anteromedial portal allows
      a more anatomical placement on the lateral femoral condyle and higher knee
      stability than does transtibial reconstruction.In the current study, the femoral
      tunnel was drilled with transtibial (n=6) and anteromedial (n=6) portal
      techniques in 12 cadaveric knees. With appropriate landmarks inserted into bone
      tunnels, the direction and length of the tunnels were determined on
      anteroposterior and lateral radiographs. Knee stability was evaluated with a
      KT1000 arthrometer (MEDmetric Corporation, San Diego, California) and pivot shift
      test, comparing the pre- and postoperative values of both techniques. Finally,
      all knees were dissected to enhance vision of the insertion of the reconstructed
      ligament. The anteromedial portal technique led to better placement of the
      femoral tunnel in the coronal and sagittal planes, with higher knee stability
      according to the pivot shift test but not the KT1000 arthrometer. Anatomical and
      clinical results reported in the literature on transtibial and anteromedial
      portal techniques are controversial, but most of studies report better results
      with the anteromedial portal technique, especially regarding rotational
      stability. The current cadaveric study showed that the anteromedial portal
      technique provided better tunnel placement on the lateral femoral condyle in the
      coronal and sagittal planes, with an improvement in the rotational stability of
      the knee.

PMID- 22868601
TI  - Effect of donor age on patellar tendon allograft ACL reconstruction.
AB  - Anterior cruciate ligament reconstruction with patellar tendon allograft tissue
      is a common orthopedic procedure. It is unknown what effect, if any, the donor
      age has on clinical outcomes. Biomechanical studies have shown the strength of
      cadaveric patellar tendon to be independent of age, but no clinical studies have
      evaluated patient outcomes related to this variable. The purpose of this study
      was to evaluate the effect of allograft donor age on clinical outcomes of
      patients undergoing allograft anterior cruciate ligament reconstruction with
      patellar tendon allograft. Case logs were reviewed to identify primary anterior
      cruciate ligament reconstruction with allograft patellar tendon by a single
      surgeon using a standard endoscopic transtibial technique with interference screw
      fixation. Revision and multiligamentous surgeries were excluded. Seventy-seven
      patients who met these criteria were identified. Allografts were fresh-frozen,
      aseptically harvested patellar tendons from a single tissue bank. The donor age
      was obtained. Clinical outcomes were obtained by contacting patients by telephone
      and retrospective chart review. Pre- and postoperative Lysholm and Tegner knee
      scores were used for comparison.Data from 75 patients with an average follow-up
      of 24 months were obtained. Average donor age was 44 years (range, 14-65 years),
      and average patient age was 37 years (range, 18-60 years). Statistical analysis
      of pre- and postoperative Lysholm scores demonstrated statistically significant
      improvement (P<=.001). Using donor age as a continuous variable, no effect was
      found on postoperative improvement in Lysholm score or Tegner score (P=.6).

PMID- 22868602
TI  - Knee pain in patients with cancer after chemotherapy, radiotherapy, and bone
      marrow transplantation.
AB  - The causes of knee pain in patients with cancer with are different from those
      without cancer, and the purpose of this study was to evaluate these differences.
      Thirty-six patients with cancer who had knee pain who had undergone 1 or more
      modalities of treatment, including chemotherapy, radiotherapy, and bone marrow
      transplant, for a primary diagnosis of cancer were compared with a cohort of 40
      patients without cancer who had knee pain. All patients were evaluated clinically
      and underwent radiographic examination, and some underwent computed tomography or
      magnetic resonance imaging examination. Among patients with a primary diagnosis
      of cancer, the most common diagnosis was lymphoma (n=10), and the most common
      causes of knee pain were avascular necrosis of bone, osteoarthritis,
      insufficiency fractures, and septic arthritis. In 5 patients, the classical signs
      of a septic knee were not present. Other causes of knee pain included meniscus
      tear and anterior cruciate ligament rupture with instability. The most common
      diagnosis in patients without cancer was osteoarthritis of the knee. No patient
      without cancer was diagnosed with avascular necrosis, metastatic lesion, or
      insufficiency fracture. Two patients without cancer were diagnosed with septic
      arthritis of the knee. This study showed that the causes of knee pain in patients
      with cancer are different from those without cancer. Septic arthritis may present
      without the classical clinical signs in patients with cancer, and a high index of
      suspicion should be maintained for it.

PMID- 22868603
TI  - Repair of pectoralis major ruptures: single-surgeon case series.
AB  - Rupture of the pectoralis major is an uncommon injury that can lead to pain, loss
      of strength, and cosmetic deformity. The purpose of this study was to analyze the
      outcome of pectoralis major repairs by a single surgeon. Twenty-four patients who
      underwent pectoralis major repair by the senior author (M.D.L.) between May 2005
      and March 2011 were retrospectively identified. Patients were assessed at least 6
      months postoperatively with the use of various questionnaires, including the Penn
      Shoulder Score, American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder
      Assessment Form, and Single Assessment Numeric Evaluation (SANE). All patients
      were men with an injury to the sternal head of the pectoralis. Most (16/24; 67%)
      patients sustained the injury while bench or incline bench pressing. Nineteen
      (79%) patients were successfully contacted for follow-up. Of these, an average
      preinjury bench press of 318 lb (range, 145-525 lb) was restored to an average of
      264 lb (range, 100-500 lb) at follow-up. Average preoperative Penn Shoulder Score
      was 60 points (range, 33-77 points), improving to 94 points (range, 64-100
      points) at last follow-up (P=.011). Average postoperative ASES and SANE scores
      were 96 points (range, 60-100 points) and 93 points (range, 50-100 points),
      respectively. All but 1 patient were rated excellent (14/19; 74%) or good (4/19;
      21%) by the Bak criteria. Operative treatment of pectoralis major rupture yields
      high patient satisfaction and allows predictable return of comfort, range of
      motion, cosmesis, and overall limb strength, with a slightly less predictable
      return of maximum bench press strength.

PMID- 22868604
TI  - Clinical results of treatment using a clavicular hook plate versus a T-plate in
      neer type II distal clavicle fractures.
AB  - AO clavicular hook plate fixation provides more rigid fixation and good bony
      union rates for Neer type II distal clavicular fractures. However, the hook may
      cause rotator cuff tears and subacromial impingement, which adversely affect the
      clinical results. T-plate fixation is another surgical method of treatment for
      unstable clavicle fractures, and its clinical efficacy has been demonstrated. The
      purpose of this study was to compare the clinical outcomes of AO clavicular hook
      plate and T-plate fixation for Neer type II distal clavicular fractures. Forty
      two patients with Neer type II fractures were divided into 2 groups. The hook
      plate group comprised 23 patients who underwent hook plate fixation, and the T
      plate group comprised 19 patients who underwent distal radius volar locking T
      plate fixation. Hook plates were removed 3 to 14 months postoperatively in 15
      patients because of shoulder function limitations. All patients were evaluated
      postoperatively for shoulder pain, activities of daily living, range of motion,
      strength, and satisfaction according to the University of California, Los Angeles
      (UCLA) Shoulder rating scale. All fractures in the 2 groups achieved stable
      fixation and bony union. Both groups yielded similar outcomes with regard to
      shoulder strength and patient satisfaction (P=.207 and P=.398, respectively).
      Significant differences existed between the 2 groups in the mean scores of
      shoulder pain, activities of daily living, range of motion, and total UCLA score
      (P=.001, P=.011, P=.038, and P=.001, respectively). More patients (74%) in the
      hook plate group had mild to severe shoulder pain than in the T-plate group
      (16%). However, shoulder pain was relieved and function improved significantly
      after removal of the hook plate (P=.001).

PMID- 22868605
TI  - Therapeutic effects of volar anatomical plates versus locking plates for volar
      Barton's fractures.
AB  - Volar Barton's fractures are uncommon and extremely unstable. Various surgical
      techniques have been reported in the literature, but open reduction and internal
      fixation using a volar plate system is currently advocated for the treatment of
      volar Barton's fractures. The purpose of this study was to compare the
      therapeutic effects of volar anatomical plates and volar locking plates in the
      treatment of volar Barton's fractures. A retrospective comparative study was
      performed of 33 patients with volar Barton's fractures treated between October
      2005 and November 2010. One group was treated with a volar anatomical plate
      (n=16) and the other with volar locking plates (n=17). Radiological and
      functional results were compared between groups. All patients' fractures healed.
      Mean union time in the anatomical plate group was 12.93 weeks and in the locking
      plate group was 11.76 weeks (P>.05). No significant difference was noted between
      the 2 groups in terms of radial inclination, volar tilt, and ulnar variance. No
      significant differences were noted between the 2 groups in Disabilities of the
      Arm, Shoulder and Hand scores; however, according to Sarmiento's modification of
      the Gartland and Werley score, the excellent and good rate was 75% in the
      anatomic plate group and 94.1% in the locking plate group, which was
      statistically significant (P<.05). Anatomical and locking plates give
      satisfactory results in the treatment of volar Barton's fractures, but locking
      plates may provide better wrist function recovery.

PMID- 22868606
TI  - Long-term outcomes of arthroscopic debridement and thermal shrinkage for isolated
      partial intercarpal ligament tears.
AB  - A retrospective analysis was performed based on the medical records and imaging
      studies of 16 wrists (14 patients) with isolated partial intercarpal ligament
      tears (scapholunate ligament: 6 wrists, lunotriquetral ligament, 10 wrists)
      treated with arthroscopic debridement and thermal shrinkage. Three wrists had
      Geissler grade 1 tears and 13 wrists had grade 2 tears. Mean follow-up was 52.8
      months. Overall pain visual analog scale scores improved significantly (P<.05) at
      rest and during activities of daily living and heavy manual work. Mean flexion
      extension arc was 136.5 degrees . Mean postoperative grip strength was 106 lb,
      which was significantly better than preoperative grip strength. Mean modified
      Mayo wrist score was 70 preoperatively and 94.7 postoperatively, a significant
      improvement. Overall functional outcomes according to the modified Mayo wrist
      score were rated as excellent in 13 wrists and good in 3. No patient had
      radiographic evidence of instability or arthritic changes. The scapholunate and
      lunotriquetral intervals in all patients were less than 3 mm on neutral and
      pronation grip radiographs. On lateral radiographs, no signs of intercalated
      segmental instability were seen, with a mean scapholunate angle of 55.3 degrees .
      The results of this study suggest that arthroscopic debridement and thermal
      shrinkage provide symptomatic pain relief and prevention of intercarpal
      instability for a significant period of time in patients with partial intercarpal
      ligament tear.

PMID- 22868607
TI  - Immediate weight bearing of comminuted supracondylar femur fractures using locked
      plate fixation.
AB  - Comminuted supracondylar femur fractures (AO-OTA 33A3) are commonly treated with
      locked plates. Weight bearing is generally restricted for 6 to 12 weeks until
      radiologic evidence exists of sufficient callous to support weight bearing.
      Recent clinical studies have reported high nonunion rates with distal femur
      locked plates. In an attempt to induce beneficial motion across the fracture
      site, some studies have recommended earlier weight bearing. The purpose of the
      current study was to determine the biomechanical feasibility of an immediate
      weight-bearing rehabilitation protocol to encourage healing of distal femur
      fractures treated with lateral locked plate fixation.Sixteen fresh-frozen
      cadaveric femora were used for this study. A 2.5-cm supracondylar gap osteotomy
      was made. Ten-hole, 4.5-mm distal femur locking plates were used with a
      standardized screw configuration that maximized the working length. The specimens
      were placed in a servohydraulic testing machine and axially loaded
      (unidirectional) at 1 Hz for up to 200,000 cycles. Failure was defined as 1 cm of
      deformation of the construct. The staircase method was used to determine the
      fatigue limit of the construct. The fatigue limit was calculated to be 1329+/-106
      N. No specimen failed through the non-locking diaphyseal screws. Plastic
      deformation, when present, occurred at the metaphyseal flare of the plate. The
      fatigue limit of the locked plate constructs equaled 1.9 times body weight for an
      average 70-kg patient over a simulated 10-week postoperative course. Given that
      distal femoral loads during gait have been estimated to be more than 2 times body
      weight, the data from this study do not support immediate full weight bearing.

PMID- 22868608
TI  - Influence of prereferral surgery in soft tissue sarcoma: 10 years' experience in
      a single institution.
AB  - Soft tissue sarcomas are a group of rare mesenchymal neoplasms comprising 0.8% of
      all malignant tumors. Workup should include medical history, physical
      examination, magnetic resonance imaging, biopsy, and thoracoabdominal computed
      tomography scan, in that order. Centralized multimodality treatment in a cross
      disciplinary setting is mandatory. Treatment not according to current clinical
      practice guidelines is a common problem before referral to a specialized
      institution. The purpose of this 10-year, single-institution review was to
      investigate the influence of curative surgery on outcome, with a special emphasis
      on surgery before referral. A cohort of 266 patients who underwent curative
      surgery for soft tissue sarcoma between 1998 and 2008 was analyzed. One hundred
      thirty-one (49%) patients underwent surgery contrary to current clinical
      guidelines before referral, most (73%) at primary care units. One hundred
      thirteen (86%) of these patients underwent surgery without previous biopsy with a
      higher rate of intralesional margins (P<.001), a smaller mean diameter of primary
      lesion (P<.001), a higher rate of subcutaneous situs (P<.001), a lower mean
      American Joint Committee on Cancer score (P=.008), a higher rate of additional
      plastic surgery after re-resection (eg, flap surgery) (P<.001), and a longer
      period before referral (P<.001). No influence on survival, local recurrence, or
      metastasis existed. Prereferral surgery necessitating re-resection has no
      influence on survival but leads to an unfavorable clinical course. More effort
      should be made to improve awareness and referral modalities for general
      practitioners and physicians at community hospitals.

PMID- 22868609
TI  - Analysis of CT-based navigation system for pedicle screw placement.
AB  - The incidence of pedicle screw breech varies based on anatomic location, body
      habitus, surgeon experience, spinal deformity, and surgical technique. Pedicle
      breeches have been reported to occur in up to 40% of screws. The purpose of this
      retrospective study was to compare the rates of revision of pedicle screw
      placement when using intraoperative C-arm vs O-arm (Medtronic, Memphis,
      Tennessee) assessment of pedicle screws. An economic analysis was also performed
      based on the estimated cost of pedicle screw revision. Four (1%) of 386 control
      patients required pedicle screw revision for a breeched pedicle screw not
      identified with intraoperative C-arm fluoroscopy. In the study group, none of the
      331 patients returned to the operating room when O-arm was used to assess pedicle
      screw placement. Based on the 1% rate of returning to the operating room in the
      control group, the annual rate of cases nationwide requiring pedicle screw
      revision would be approximately 2300, with a cost of approximately
      $40,595,000.These results suggest that the use of intraoperative O-arm can reduce
      the need for revision of a breeched pedicle screw. This can potentially lead to a
      major cost savings.

PMID- 22868610
TI  - Sandwich vertebral fracture in the study of adjacent-level fracture after
      vertebral cement augmentation.
AB  - The literature is inconclusive on the development of adjacent-level vertebral
      fracture after initial cement augmentation. A preliminary hypotheses is that
      cement injection exaggerates force transmission to the adjacent vertebral bodies,
      thereby predisposing those levels to future fractures. A sandwich vertebra is an
      intact vertebral body located between 2 previously cemented vertebrae. The
      purpose of this study was to determine whether the risk of adjacent-level
      fracture increased due to load shift after a cement injection procedure. The
      authors retrospectively investigated the rate of adjacent-level fracture after
      sandwiching compared with conservative treatment and determined the potential
      causative factors of sandwich vertebral fracture. Age, sex, weight, height, body
      mass index, follow-up period, and location of sandwich level (T10-L2 or nonT10-L2
      junction) were assessed. Surgical variables, including surgical procedure
      (vertebroplasty or balloon kyphoplasty), surgical approach (through uni- or
      bilateral pedicle), volume of cement injected into the painful vertebrae, cement
      leakage into the intervertebral disk, cumulative number of treated levels, and
      pre- and postoperative kyphotic angulation of the sandwich region, were also
      analyzed. Nine of 42 sandwiched levels developed fatigue fractures, whereas 11 of
      71 patients treated with conservative therapy sustained new vertebral fractures
      adjacent to the treated levels. Only preoperative kyphotic angulation was the
      variable positively associated with sandwich vertebral fracture at follow-up
      (P=.021). Although subjected to double load shifts, the sandwich vertebra was not
      prone to structural failure. Thus, cement augmentation protocol does not increase
      the incidence of adjacent vertebral fracture.

PMID- 22868611
TI  - Surgical strategy for ossification of the posterior longitudinal ligament in the
      cervical spine.
AB  - Ossification of the posterior longitudinal ligament is a common cause of cervical
      myelopathy, and controversy remains regarding surgical options. Between January
      2004 and December 2007, a total of 164 patients with ossification of the
      posterior longitudinal ligament in the cervical spine who underwent surgical
      treatment at the authors' institution were included in this study. The choice of
      surgical option was based on pathological extent and cervical alignment. Short
      segment pathology was treated via the anterior approach and long-segment
      pathology via the posterior approach. When the posterior approach was selected,
      laminoplasty was performed for the patients with cervical lordosis and
      laminectomy with fusion for those with cervical kyphosis. Consequently, anterior
      corpectomy and fusion was performed in 91 patients, laminoplasty in 41 patients,
      and laminectomy and instrumented fusion in 32 patients. The Japanese Orthopedic
      Association scoring system was used to evaluate patients' neurological status,
      and related complications were also recorded. Clinical results between different
      approaches and techniques were compared at mid-term follow-up. Based on the
      results of this study and a review of previous literature, no significant
      differences existed between different approaches and techniques for patients with
      mild ossification of the posterior longitudinal ligament, but anterior corpectomy
      and fusion had significantly better results in patients with severe ossification
      of the posterior longitudinal ligament. With respect to the posterior approach,
      laminectomy and instrumented fusion improved the surgical results of patients
      with cervical kyphosis, but a high incidence of C5 palsy existed simultaneously.

PMID- 22868612
TI  - Effects of interleukin-1 receptor antagonist on collagen and matrix
      metalloproteinases in stress-shielded achilles tendons of rats.
AB  - Based on previous studies showing that interleukin-1 (IL-1) significantly
      increased after stress shielding, this article reports further research into the
      possible therapeutic applications of IL-1 receptor antagonist (IL-1Ra). Forty
      rats whose left Achilles tendons were denervated and completely stress shielded
      were divided into 5 groups: 2-week phosphate-buffered saline (PBS); 4-week PBS; 2
      week IL-1Ra; 4-week IL-1Ra; and normal control. The Achilles tendons were tested
      morphologically, and the changes in collagen I and III, matrix metalloproteinases
      (MMP)-1 and -3, and tissue inhibitors of metalloproteinase (TIMP)-1 were
      determined. The collagen fibrils in the IL-1Ra groups were morphologically more
      similar to those in the control group than to those in the PBS groups. The
      collagen I levels increased in the 2-week groups. Significant differences existed
      between the PBS and IL-1Ra groups at 4 weeks. The MMP-1 level increased
      dramatically after stress shielding and increased less in the 2-week IL-1Ra group
      than in the 2-week PBS group. The degree of decrease of MMP-3 in the IL-1Ra
      groups was significantly less than that in the PBS groups. The collagen III and
      TIMP-1 levels continued to increase, and no difference was found between the PBS
      and IL-1Ra groups. Interleukin-1 receptor antagonist prevented morphological
      deterioration and collagen metabolism of the denervated Achilles tendons after
      stress shielding, likely by inhibiting the decline of MMP-3 and increasing MMP-1
      levels at an early stage.

PMID- 22868613
TI  - Cuff width increases the serum biochemical markers of tourniquet-induced skeletal
      muscle ischemia in rabbits.
AB  - Tourniquet application is a widely accepted adjuvant technique in extremity
      surgery. The purpose of this prospective, randomized trial was to evaluate the
      effect of cuff width on skeletal muscle ischemia-reperfusion injury. A 2- or 4-cm
      wide curved tourniquet cuff was applied around the midthigh of 36 New Zealand
      White rabbits and inflated to a pressure of 200 or 400 mm Hg for 2 hours: group
      A=2 cm to 200 mm Hg; group B=2 cm to 400 mm Hg; group C=4 cm to 200 mm Hg; group
      D=4 cm to 400 mm Hg. Blood levels of potassium, lactic acid, urea, lactic
      dehydrogenase, and creatinine phosphokinase MM isoenzyme (CPK-MM) were measured
      as basic indicators for limb ischemia before tourniquet inflation and 1, 5, and
      30 minutes after cuff release.Potassium values did not differ among the 4 groups.
      Lactic acid and urea concentrations were always higher in the 400 mm Hg groups (B
      and D) (P<.001). However, cuff width did not affect their levels (P>.16). Lactic
      dehydrogenase and CPK-MM values were also greater in the 400 mm Hg groups at all
      times (P<.001). Further subgroup analysis of 200 mm Hg pressure groups showed
      higher lactic dehydrogenase (P<.02) but not CPK-MM (P>.9) concentrations in group
      C than in group A during the 30-minute period. At 400 mm Hg, lactic dehydrogenase
      and CPK-MM values were higher in group D compared with group B only 30 minutes
      after cuff deflation (P<.001). Broad tourniquets are associated with
      significantly greater and prolonged elevation of serum biochemical markers of
      inducible skeletal muscle ischemia-reperfusion injury compared with narrow ones.
      This difference is more prominent when a wide cuff is inflated to a high
      pressure.

PMID- 22868614
TI  - Analysis of the basic science section of the orthopaedic in-training examination.
AB  - Since 1963, the Orthopaedic In-Training Examination (OITE) has been administered
      to orthopedic residents to assess residents' knowledge and measure the quality of
      teaching within individual programs. The OITE currently consists of 275 questions
      divided among 12 domains. This study analyzed all OITE basic science questions
      between 2006 and 2010. The following data were recorded: number of questions,
      question taxonomy, category of question, type of imaging modality, and
      recommended journal and book references. Between 2006 and 2010, the basic science
      section constituted 12.2% of the OITE. The assessment of taxonomy classification
      showed that recall-type questions were the most common, at 81.4%. Imaging
      modalities typically involved questions on radiographs and constituted 6.2% of
      the OITE basic science section. The majority of questions were basic science
      questions (eg, genetics, cell replication, and bone metabolism), with an average
      of 26.4 questions per year. The Journal of Bone & Joint Surgery (American Volume)
      and the American Academy of Orthopaedic Surgeons' Orthopaedic Basic Science were
      the most commonly and consistently cited journal and review book, respectively.
      This study provides the first review of the question content and recommended
      references of the OITE basic science section. This information will provide
      orthopedic trainees, orthopedic residency programs, and the American Academy of
      Orthopaedic Surgeons Evaluation Committee valuable information related to
      improving residents' knowledge and performance and optimizing basic science
      educational curricula.

PMID- 22868615
TI  - Is the 22 modifier worth it?
AB  - The 22 modifier is a Current Procedural Terminology code modifier that allows
      surgeons to receive additional reimbursement for complex procedures. The goal of
      this study was to evaluate the rate of, time to, and factors affecting
      reimbursement for 22-modifier cases filed by orthopedic surgeons. The authors
      reviewed the charts and billing data of the 150 noncharity spine and total joint
      replacement cases filed with a 22 modifier at 1 academic institution from 2004
      through 2011. Of those 150 cases, 63 (42%) were reimbursed at a rate higher than
      the fee schedule. For all 150 cases, the mean amount and mean percentage of
      additional reimbursement were -$86+/-$1966 (P=.7) and 5.5%+/-37% (P=.04),
      respectively. The mean reimbursement time for private and public payers was 138+/
      126 days (P<.001) and 118+/-129 days (P<.001), respectively (standard time, 30
      and 15 days, respectively). The mean present values of the amount and percentage
      received compared with the fee schedule were -$144+/-$1966 (P=.8) and 4.1%+/-37%
      (P=.09), respectively (discount rate, 5%). Anatomic variant was the only cited
      reason that increased the probability of additional reimbursement (P=.016).
      Citing that the case required additional time had no bearing on additional
      reimbursement. The authors conclude that additional reimbursement with the 22
      modifier is inconsistent, has significant payment delays, and is not worth the
      effort for total joint replacement or spine surgery.

PMID- 22868616
TI  - Catastrophic fracture of a stable metal acetabular component.
AB  - Various modes of failure of primary and revision total hip arthroplasty have been
      well documented in the literature over the past 30 years. Concerns over
      polyethylene wear, osteolysis, and hypersensitivity reactions leading to
      component loosening and early revision have been evaluated and reported in the
      literature. Routine follow-up is important to monitor for postoperative issues
      that might lead to the subsequent need for revision.This article describes a case
      of a 64-year-old man who initially presented 11 years prior with an
      intertrochanteric fracture, which failed secondary to varus alignment and femoral
      head osteonecrosis. The fixation was converted to a total hip replacement using
      the S-ROM system (DePuy, Warsaw, Indiana). Subsequently, the patient was lost to
      follow-up after primary total hip arthroplasty and presented with a catastrophic
      fracture of the metal acetabular cup system. The failure was suggested by
      clinical presentation and confirmed by imaging studies showing a fractured
      acetabular shell with femoral head prosthesis resting in the superolateral ileum.
      The contributing factors that resulted in mechanical failure were polyethylene
      wear and component fracture. The acetabular component was revised with an in
      growth cementless trabecular metal multihole cup (Zimmer, Warsaw, Indiana) with
      bone grafting of acetabular defects.Routine assessments help educate patients and
      allow careful monitoring by physicians while establishing a radiographic timeline
      for the identification, progression, or lack of postoperative complications.

PMID- 22868617
TI  - Backout of the helical blade of proximal femoral nail antirotation and
      accompanying fracture nonunion.
AB  - This article describes a case of backout of the helical blade, a rare
      complication of proximal femoral nail antirotation. A 31-year-old man had
      sustained a trochanteric fracture of his right femur. Fracture fixation using
      proximal femoral nail antirotation and autologous bone grafting 7 months later
      were performed at another hospital. However, bony union was not obtained, and the
      patient's pain and limp persisted. Therefore, he presented to the current
      authors. A radiograph taken at presentation revealed backout of the helical blade
      and fracture nonunion. A radiograph taken 1 month later showed a more advanced
      backout of the helical blade. The authors performed exchange nailing supplemented
      with transplantation of peripheral blood CD34-positive cells and autologous bone
      grafting. The proximal femoral nail antirotation was revised to a long gamma 3
      nail, and a U-lag screw was used to obtain better stability. The postoperative
      course was uneventful. The patient regained ambulation without pain or support at
      12 weeks postoperatively. Radiographic bony union was completed 9 months
      postoperatively. At 1-year follow-up, he could run and stand on the previously
      injured leg and had returned to work. Backout of the helical blade should be
      considered as a possible complication of proximal femoral nail antirotation.
      Incomplete fixation of the helical blade is the possible reason for backout. The
      use of a helical blade in young patients may cause difficulty in insertion and
      result in incomplete fixation.

PMID- 22868618
TI  - Extra-articular synovial fluid extravasation following operative fixation of an
      osteochondral fracture of the patella.
AB  - Osteochondral fracture of the patella following a lateral patellar dislocation
      can be treated with operative and nonoperative techniques that are dictated by
      the clinical presentation. In the presence of large fragments following acute
      fractures, arthroscopic retrieval and fixation are advocated, whereas smaller
      displaced fragments may be removed and discarded as loose bodies. Several methods
      of fixation exist for osteochondral fractures of the patella, including the use
      of cannulated and noncannulated screws.This article describes a case of an elite
      competitive swimmer who sustained a lateral patellar dislocation with a large
      osteochondral fracture of the patella that was treated with open reduction and
      fixation using absorbable cannulated screws in an inside-out fashion. In the
      early postoperative period, the patient developed a symptomatic synovial fluid
      fistula through a cannulated screw to the prepatellar space. The diagnosis of
      this condition was made clinically and confirmed with noncontrast magnetic
      resonance imaging 6 weeks postoperatively. The symptoms of pain, skin erythema,
      and swelling were self-limited and eventually resolved with observation, allowing
      the athlete to return to his previous activity level. Magnetic resonance imaging
      3 years postoperatively showed the complete resolution of the fluid
      extravasation. Extra-articular synovial fluid extravasation is as a rare
      complication following routine knee arthroscopy, accounting for 3.2% of the
      complications. This article describes a rare, self-limited complication following
      open fixation of an osteochondral fracture of the patella.

PMID- 22868619
TI  - Isolated tear of the pectoralis minor tendon in a high school football player.
AB  - Multiple pectoralis major tendon tears have been reported in the literature;
      however, isolated rupture of the pectoralis minor tendon is rare and has been
      reported 3 times (4 patients).This article describes a case of an isolated
      pectoralis minor tendon tear in a male high school football player after a
      traumatic injury. The patient was injured while making a tackle and leading with
      his arm and chest. He presented with left anterior shoulder and chest wall pain
      with direct tenderness on palpation over the coracoid. Magnetic resonance imaging
      of the chest revealed an isolated tear of the pectoralis minor tendon with slight
      retraction and significant edema in the muscle belly. The patient returned to
      full activities after conservative management.Although rare, the diagnosis of
      pectoralis minor tendon rupture should be considered in patients who sustain a
      contact injury to the shoulder with tenderness on palpation over the coracoid.
      The mechanism of injury can be related to a direct anterior force to the
      shoulder, forced external rotation of the arm in slight abduction, or with the
      arm in extension and shoulder in flexion (eg, blocking in football). The
      diagnosis can be confirmed with magnetic resonance imaging when edema exists on
      the medial aspect of the coracoid and extends into the muscle belly. Physical
      therapy with scapular stabilization exercises and avoidance of abduction and
      active adduction can be successful in returning these patients to their previous
      activity levels.

PMID- 22868620
TI  - Parallel plating for a sternomanubrial dislocation.
AB  - Sternomanubrial dislocations are rare injuries. Although few cases of this injury
      have been reported in the literature, the etiology has varied widely: trampoline
      injury, seizures, falls from height, sporting injuries, gradual deformities from
      spine fractures, and motor vehicle collisions. This injury has been classified
      into 2 types: in type I, the sternal body is displaced posteriorly to the
      manubrium, and in the more common type II, the sternal body is displaced
      anteriorly. The sternomanubrial joint is an amphiarthroidal joint that bears
      hyaline cartilage on both surfaces connected by a fibrocartilage meniscus. It
      serves a protective role to vital thoracic structures and is an anterior
      stabilizing strut to the thorax, assisting the thoracic spine in upright
      stability. It is important to not ignore type I dislocations because posterior
      sternum displacement is a harbinger of injury to the pulmonary tree, heart, and
      esophagus. Chronic instability at this joint can lead to dyspnea and dysphasia
      due to sternum displacement. In the right scenario, type II injuries are
      occasionally treated conservatively with palliative treatment until the sternum
      heals with malformation. This article describes the case of a 20-year-old man who
      was treated surgically for symptomatic type II sternomanubrial dislocation with
      dual anterior locked plating. Locked plating gives the benefit of unicortical
      fixation, with the screws and plate acting as a unit to resist motion. Screw
      pullout and failure is less common, and the construct is more resistant for this
      application. The patient returned to full participation in activities of daily
      living and military duty 4 months postoperatively.

PMID- 22868621
TI  - Arthroscopically assisted percutaneous fixation and bone grafting of a glenoid
      fossa fracture nonunion.
AB  - Arthroscopy is commonly used for evaluating intra-articular fracture patterns and
      assessing postfixation reduction; however, the use of arthroscopy for the
      definitive treatment of articular fracture nonunion has not been reported. This
      article describes a case of symptomatic glenoid fossa fracture nonunion that was
      successfully treated with arthroscopically assisted percutaneous screw fixation
      and bone grafting. A 48-year-old laborer sustained a glenoid fossa fracture
      following a fall from a height. An initial period of nonoperative management was
      attempted; however, the patient reported continued shoulder pain during his
      rehabilitation course. Imaging 5 months after injury showed no osseous union at
      the fracture. Using an arthroscopically assisted technique, percutaneous fixation
      and bone grafting of the nonunion with cancellous allograft was performed.
      Postoperatively, the patient progressed through a structured therapy program, and
      his pain improved. A computed tomography scan 4 months postoperatively showed
      osseous union at the fracture site. To the authors' knowledge, this is the first
      report in the literature of definitive arthroscopically assisted bone grafting
      and percutaneous fixation of a diarthrodial joint nonunion. Advantages of
      arthroscopic fixation of glenoid fossa fracture nonunion include avoiding
      potential axillary nerve injury and preserving the native subscapularis
      insertion, which may be important if subsequent procedures require access to the
      anterior access to the joint.

PMID- 22868622
TI  - Isolated ring finger flexor digitorum profundus entrapment after closed reduction
      and intramedullary fixation of both-bone forearm fracture.
AB  - Flexor tendon entrapment after a pediatric forearm fracture is a rarely reported
      complication that is often diagnosed late. Flexor tendon entrapment is more
      frequently reported after distal forearm fractures, and possible etiologies
      include fibrosis secondary to hemorrhage at the fracture site and simple
      entrapment of the muscle belly.This article describes a case of ring finger
      flexor digitorum profundus entrapment in a 12-year-old boy with a closed both
      bone forearm fracture that was treated with closed reduction and intramedullary
      nail fixation. Preoperatively, the patient had full flexion and extension of all
      fingers. The entrapment was noted at the first postoperative follow-up when the
      patient could fully extend the ring finger proximal interphalangeal joint but was
      unable to concomitantly extend the metacarpal phalangeal joint. Magnetic
      resonance imaging and ultrasound were obtained to identify the entrapment site.
      Intraoperatively, a portion of the flexor digitorum profundus musculotendinous
      junction was entrapped in the fracture site. After release of the entrapment, the
      patient gained immediate passive range of motion. Subsequently, the hardware was
      removed, and the patient healed and regained full ring finger function. To the
      authors' knowledge, this is the only report of isolated ring finger flexor
      digitorum profundus entrapment after closed reduction and intramedullary fixation
      of a pediatric forearm fracture. The authors recommend vigilant physical
      examination of passive and active range of motion of all digital joints with the
      wrist in flexion and extension before and after bony manipulation.

PMID- 22868623
TI  - Atraumatic acute carpal tunnel syndrome in a patient taking dabigatran.
AB  - Acute carpal tunnel syndrome is an uncommon diagnosis most often related to blunt
      trauma requiring immediate surgical decompression to avoid serious sequelae.
      Patients who present with bleeding-related acute carpal tunnel syndrome tend to
      have severe pain, rapid onset of swelling, and neurologic symptoms that appear
      early and progress rapidly secondary to mass effect. Acute carpal tunnel syndrome
      can occur in anticoagulated patients spontaneously or after minor trauma. This
      article describes a case of a 57-year-old man with progressive pain and
      paresthesias in the median nerve distribution after reaching for a picture frame.
      He was taking dabigatran, a direct thrombin inhibitor, for atrial fibrillation.
      He developed acute carpal tunnel syndrome secondary to spontaneous bleeding into
      the carpal canal and flexor tenosynovium with hematoma formation requiring
      surgical decompression. He reported immediate pain relief postoperatively, had no
      further bleeding complications, and regained full median nerve function within 2
      months.Dabigatran has gained recent popularity for the treatment of atrial
      fibrillation. Unlike warfarin, its use does not involve regular laboratory
      monitoring or dose titration. The risks and benefits of dabigatran should be
      considered carefully by the prescriber, particularly in patients taking
      medications that may alter its metabolism. Aspirin and nonsteroidal anti
      inflammatory drugs may have effects similar to dabigatran and may increase the
      risk of bleeding problems. Should acute carpal tunnel syndrome occur, the authors
      recommend prompt surgical decompression rather than conservative management. The
      modification of anticoagulant therapy should be considered on a case-by-case
      basis.

PMID- 22868624
TI  - Ankle fracture following hip arthroscopy.
AB  - This article describes a case of an ankle fracture following hip arthroscopy. A
      58-year-old woman underwent hip arthroscopy for a labral tear. She was placed in
      a lateral decubitus position with her foot in a padded boot. Traction was
      maintained for approximately 30 minutes. She was instructed to bear weight as
      tolerated with crutches postoperatively. At 2-week follow-up, she reported
      ipsilateral ankle pain. Radiographs revealed a minimally displaced medial
      malleolus fracture. She was treated with a cast followed by a cam walker boot and
      successfully went on to complete union and resolution of her symptoms. The
      following risk factors exist for ankle fracture after hip arthroscopy: history of
      ankle sprains, ligamentous laxity (more common in women), and small feet with
      large calves (more likely to become plantarflexed during traction). Distraction
      performed with the ankle rotated is also likely to place added stress on the
      medial or lateral ligamentous structures. It is important to counsel patients
      preoperatively about the risk of ankle pain after hip arthroscopy, to be aware of
      the possibility of ankle pathology postoperatively, and to have a low threshold
      for ordering radiographs. Radiographs are warranted if patients continue to have
      ankle pain after 72 hours postoperatively.

PMID- 22868625
TI  - Multicentric epithelioid angiosarcoma of bone.
AB  - Bone epithelioid angiosarcoma is rare and generally shows positive immunostaining
      for epithelial markers. Multicentric bone epithelioid angiosarcoma is easily
      misdiagnosed as carcinoma, including metastatic carcinoma, multiple myeloma, and
      multiple lymphoma of bone. This article describes a case of multicentric bone
      epithelioid angiosarcoma. The patient was first misdiagnosed as having metastatic
      carcinoma. Examination showed osteolytic lesions in the bilateral heels and the
      lower left humerus. The diagnosis was confirmed postoperatively and corrected
      after immunohistochemical analysis of the biopsy. The immunohistochemical
      analysis revealed that the tumor mass was strongly positive for CD31, factor
      VIII, vimentin, and neuron-specific enolase. The patient refused chemotherapy and
      died of lung metastasis 4 months postoperatively.Most bone epithelioid
      angiosarcomas are immunopositive for epithelial markers (ie, keratin,
      cytokeratin, high-molecular-weight keratin, and epithelial membrane antigen),
      vascular endothelial markers (ie, CD31, CD34, and von Willebrand factor), and
      factor VIII-associated antigen. Bone epithelioid angiosarcoma shows a relatively
      high degree of malignancy. Patients often die of distant metastasis, including
      those found in the lung and lymph node tissue. A wide excision of epithelioid
      angiosarcoma should be performed during the operation of the primary tumor. A
      better understanding of the clinicopathologic features of this disease may help
      to clarify the confusion, provide better treatment, and improve the clinical
      prognosis.

PMID- 22868626
TI  - Single-level calcified cervical disk herniation in a 13-year-old girl.
AB  - This article describes a case of a 13-year-old girl with single-level calcified
      cervical disk herniation. The patient was treated conservatively for a
      symptomatic intervertebral calcification that caused neurological compression,
      and the data were reviewed retrospectively. Previous reports have shown that the
      natural history of the disease is self-limiting with a benign course and an
      excellent prognosis. However, on rare occasions when the calcified nucleus
      pulposus herniates into the spinal canal and compresses the spinal cord or its
      roots, neurological abnormalities can occur, such as radiculopathy and
      myelopathy. This also raises the question of whether operative therapy will
      eventually be necessary. In the current case, conservative treatment was applied.
      Plain radiographs are usually sufficient to determine the presence and extent of
      a calcified cervical disk, and computed tomography or magnetic resonance imaging
      can detect an associated disk herniation. Conservative treatment with antalgics,
      muscle relaxants, neurotrophic drugs, and a cervical collar were applied. The
      patient was completely free of symptoms 3 weeks after the initial treatment.
      Magnetic resonance imaging indicated complete vertebral canal clearance at final
      follow-up. Cervical intervertebral disk calcification and herniation is a rare
      disorder in children with an obscure etiology but a good prognosis. Conservative
      therapy produces satisfactory results, even if clinical symptoms due to nerve
      root or spinal cord compression are present. Surgical treatments are only
      suitable in rare cases with severe progressive radicular pain or neurological
      deficit.

PMID- 22868627
TI  - Nanoengineered glycan sensors enabling native glycoprofiling for medicinal
      applications: towards profiling glycoproteins without labeling or liberation
      steps.
AB  - Nanoengineered glycan sensors may help realize the long-held goal of accurate and
      rapid glycoprotein profiling without labeling or glycan liberation steps. Current
      methods of profiling oligosaccharides displayed on protein surfaces, such as
      liquid chromatography, mass spectrometry, capillary electrophoresis, and
      microarray methods, are limited by sample pretreatment and quantitative accuracy.
      Microarrayed platforms can be improved with methods that better estimate kinetic
      parameters rather than simply reporting relative binding information. These
      quantitative glycan sensors are enabled by an emerging class of nanoengineered
      materials that differ in their mode of signal transduction from traditional
      methods. Platforms that respond to mass changes include a quartz crystal
      microbalance and cantilever sensors. Electronic response can be detected from
      electrochemical, field effect transistor, and pore impedance sensors. Optical
      methods include fluorescent frontal affinity chromatography, surface plasmon
      resonance methods, and fluorescent carbon nanotubes. After a very brief primer on
      glycobiology and its connection to medicine, these emerging systems are
      critically reviewed for their potential use as core sensors in future
      glycoprofiling tools.

PMID- 22868628
TI  - Aliphatic beta-nitroalcohols for therapeutic corneoscleral cross-linking: corneal
      permeability considerations.
AB  - PURPOSE: Our recent tissue cross-linking studies have raised the possibility of
      using aliphatic beta-nitroalcohols (BNAs) for pharmacologic, therapeutic corneal
      cross-linking. The present study was performed to determine the permeability of
      BNAs and to explore the use of permeability-enhancing agents. METHODS: Ex vivo
      rabbit corneas were mounted in a typical Franz diffusion chamber. BNA
      permeability was determined by assaying the recipient chamber over time using a
      modification of the Griess nitrite colorimetric assay. The apparent permeability
      coefficient (Ptot) was determined for 2 mono-nitroalcohols [2-nitroethanol (2ne)
      and 2-nitro-1-propanol (2nprop)], a nitrodiol [2-methyl-2-nitro-1,3-propanediol
      (MNPD)], and a nitrotriol [2-hydroxymethyl-2-nitro-1,3-propanediol (HNPD)].
      Permeability-enhancing effects using benzalkonium chloride (BAC) (0.01% and
      0.02%), ethylenediaminetetraacetic acid (0.05%), and a combination of 0.01% BAC +
      0.5% tetracaine were also studied. RESULTS: The Ptot (+/-SE) values (in
      centimeters per second) were as follows: 4.33 * 10 (+/-9.82 * 10) for 2ne
      [molecular weight (MW) = 91 Da], 9.34 * 10 (+/-2.16 * 10) for 2nprop (MW = 105
      Da), 4.37 * 10 (+/-1.86 * 10) for MNPD (MW = 135 Da), and 8.95 * 10 (+/-1.93 *
      10) for HNPD (MW = 151 Da). Using the nitrodiol, permeability increased
      approximately 2-fold using 0.01% BAC, 5-fold using 0.02% BAC, and 5-fold using
      the combination of 0.01% BAC + 0.5% tetracaine. No effect was observed using
      0.05% ethylenediaminetetraacetic acid. CONCLUSIONS: The results indicate that the
      corneal epithelium is permeable to BNAs, with the apparent permeability
      corresponding to MW. The findings are consistent with previous literature
      indicating that the small size of these compounds (<10A) favors their passage
      through the corneal epithelium via the paracellular route. This information will
      help to guide dosing regimens for in vivo topical cross-linking studies.

PMID- 22868629
TI  - Seasonal trends of microbial keratitis in South India.
AB  - PURPOSE: Previous studies suggest that fungal keratitis is more common in hot
      humid climates and that bacterial keratitis is independent of seasonal variation.
      This study analyzes seasonal trends in the incidence of fungal and bacterial
      keratitis at the Aravind Eye Hospital in southeast India. METHODS: Using
      microbiology records from August 2006 to July 2009, retrospective analyses of
      infectious keratitis were performed. Bacterial and fungal keratitis incidence
      data were analyzed for seasonal patterns. RESULTS: Among the 6967 infectious
      keratitis cases, cultures were performed in 5221 (74.9%) cases; among them, 3028
      (58%) were positive. Of the culture-positive cases, 1908 (63%) and 1081 (35.7%)
      were of fungal and bacterial etiology, respectively. The predominant fungal
      organism was Fusarium spp (42.3%) and the predominant bacterial organisms were
      Streptococcus pneumoniae (35.1%), Pseudomonas aeruginosa (24.3%), and Nocardia
      spp (8.1%). Analyses revealed an uneven distribution of fungal keratitis
      throughout the year (P < 0.001) with peaks in July and January. No significant
      seasonal trend was observed for the combined bacterial keratitis group.
      CONCLUSIONS: A higher incidence of fungal keratitis occurs during the months
      corresponding to the windy and harvest seasons, during which time infection from
      vegetative corneal injury may be more likely. Robust screening efforts during
      these periods may mitigate visually debilitating sequelae from infectious
      keratitis.

PMID- 22868630
TI  - Selective photothermal therapy for breast cancer with targeting peptide modified
      gold nanorods.
AB  - In this work, we prepared polyacrylic acid (PAA) coated gold nanorods (GNRs) and
      then the targeting peptide modified GNRs. The biocompatibility and stability of
      functionalized GNRs were investigated by monitoring the surface plasmon resonance
      (SPR) absorption intensity. The efficacy of targeted thermal therapy can be
      significantly enhanced via decoration with surface-bound peptide which was
      obtained through phage display technology. In addition, the photothermal therapy
      was monitored in real time with the multi-channel function of a confocal laser
      scanning microscope (CLSM) coupled with an 808 nm laser. This selective
      photothermal therapy of GNRs is a promising candidate for phototherapeutic
      applications.

PMID- 22868631
TI  - Modified Snodgrass tubularized incised plate urethroplasty prevents fistula
      formation in hypospadias.
AB  - Urethrocutaneous fistula is a common complication after redo urethroplasty for
      hypospadias, or urethroplasty for patients with thin urethral plate. We modified
      Snodgrass' tubularized incised plate urethroplasty (STIPU) by stripping the most
      superficial skin from both sides of the U-shaped incision to expose more
      subcutaneous tissue along the suture line. Our modified STIPU would appear to be
      effective in preventing postoperative urethrocutaneous fistula formation in redo
      urethroplasty for hypospadias, and urethroplasty for patients with thin urethral
      plate.

PMID- 22868632
TI  - Yolk sac tumor of the vulva: a case report with recurrence after long-term follow
      up.
AB  - A yolk sac tumor (YST) of the vulva is extremely rare and highly malignant with
      recurrence frequently occurring within a year. This report presents the 13th
      known case of vulvar YST, with recurrence occurring after the longest known
      follow-up period so far reported in the literature.

PMID- 22868633
TI  - Adaptive inverse control of neural spatiotemporal spike patterns with a
      reproducing kernel Hilbert space (RKHS) framework.
AB  - The precise control of spiking in a population of neurons via applied electrical
      stimulation is a challenge due to the sparseness of spiking responses and neural
      system plasticity. We pose neural stimulation as a system control problem where
      the system input is a multidimensional time-varying signal representing the
      stimulation, and the output is a set of spike trains; the goal is to drive the
      output such that the elicited population spiking activity is as close as possible
      to some desired activity, where closeness is defined by a cost function. If the
      neural system can be described by a time-invariant (homogeneous) model, then
      offline procedures can be used to derive the control procedure; however, for
      arbitrary neural systems this is not tractable. Furthermore, standard control
      methodologies are not suited to directly operate on spike trains that represent
      both the target and elicited system response. In this paper, we propose a
      multiple-input multiple-output (MIMO) adaptive inverse control scheme that
      operates on spike trains in a reproducing kernel Hilbert space (RKHS). The
      control scheme uses an inverse controller to approximate the inverse of the
      neural circuit. The proposed control system takes advantage of the precise timing
      of the neural events by using a Schoenberg kernel defined directly in the space
      of spike trains. The Schoenberg kernel maps the spike train to an RKHS and allows
      linear algorithm to control the nonlinear neural system without the danger of
      converging to local minima. During operation, the adaptation of the controller
      minimizes a difference defined in the spike train RKHS between the system and the
      target response and keeps the inverse controller close to the inverse of the
      current neural circuit, which enables adapting to neural perturbations. The
      results on a realistic synthetic neural circuit show that the inverse controller
      based on the Schoenberg kernel outperforms the decoding accuracy of other models
      based on the conventional rate representation of neural signal (i.e., spikernel
      and generalized linear model). Moreover, after a significant perturbation of the
      neuron circuit, the control scheme can successfully drive the elicited responses
      close to the original target responses. 

PMID- 22868634
TI  - Prediction of stroke motor recovery using reflex stiffness measures at one month.
AB  - This study characterizes the recovery patterns of motor impairment after stroke,
      and uses neuromuscular measures of the elbow joint at one month after the event
      to predict the ensuing recovery patterns over 12 months. Motor impairment was
      assessed using the Fugl-Meyer Assessment (FMA) of the upper extremity at various
      intervals after stroke. A parallel-cascade system identification technique
      characterized the intrinsic and reflex stiffness at various elbow angles. We then
      used "growth-mixture" modeling to identify three distinct recovery classes for
      FMA. While class 1 and class 3 subjects both started with low FMA, those in class
      1 increased FMA significantly over 12-month recovery period, whereas those in
      class 3 presented no improvement. Class 2 subjects started with high FMA and also
      exhibited significant FMA improvement, but over a smaller range and at a slower
      recovery rate than class 1. Our results showed that the one-month reflex
      stiffness was able to distinguish between classes 1 and 3 even though both showed
      similarly low month-1 FMA. These findings demonstrate that, using reflex
      stiffness, we were able to accurately predict arm function recovery in stroke
      subjects over one year and beyond. This information is clinically significant and
      can be helpful in developing targeted therapeutic interventions.

PMID- 22868635
TI  - Automatic seizure detection using wavelet transform and SVM in long-term
      intracranial EEG.
AB  - Automatic seizure detection is of great significance for epilepsy long-term
      monitoring, diagnosis, and rehabilitation, and it is the key to closed-loop brain
      stimulation. This paper presents a novel wavelet-based automatic seizure
      detection method with high sensitivity. The proposed method first conducts
      wavelet decomposition of multi-channel intracranial EEG (iEEG) with five scales,
      and selects three frequency bands of them for subsequent processing. Effective
      features are extracted, such as relative energy, relative amplitude, coefficient
      of variation and fluctuation index at the selected scales, and then these
      features are sent into the support vector machine for training and
      classification. Afterwards a postprocessing is applied on the raw classification
      results to obtain more accurate and stable results. Postprocessing includes
      smoothing, multi-channel decision fusion and collar technique. Its performance is
      evaluated on a large dataset of 509 h from 21 epileptic patients. Experiments
      show that the proposed method could achieve a sensitivity of 94.46% and a
      specificity of 95.26% with a false detection rate of 0.58/h for seizure detection
      in long-term iEEG.

PMID- 22868636
TI  - Crystalline metallic Au nanoparticle-loaded alpha-Bi2O3 microrods for improved
      photocatalysis.
AB  - Crystalline metallic Au nanoparticles were loaded on alpha-Bi(2)O(3) microrods
      (Au/alpha-Bi(2)O(3)) using an Au deposition-precipitation method. The prepared
      samples were characterized by scanning electron and transmission electron
      microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and UV-vis
      diffuse reflectance spectroscopy. Upon visible light irradiation, the Au/alpha
      Bi(2)O(3) exhibits much higher photocatalytic activities than the pure alpha
      Bi(2)O(3) for the degradation of Rhodamine B and 2,4-dichlorophenol in aqueous
      solution. The role of the Au and the paths of electron transport in the
      photocatalysis of the Au/alpha-Bi(2)O(3) were investigated and discussed in
      detail based on the analysis of the photo-generated hydroxyl radicals (OH) and
      hydrogen peroxide (H(2)O(2)) in the visible light irradiated suspension of pure
      alpha-Bi(2)O(3) and Au/alpha-Bi(2)O(3). The result reveals that the Au loaded on
      alpha-Bi(2)O(3) plays a critical role in the separation of the electron and hole
      pairs by accumulating the electrons from the excited alpha-Bi(2)O(3), which is
      responsible for the enhanced photocatalytic activity.

PMID- 22868637
TI  - The chromosomes of Afrotheria and their bearing on mammalian genome evolution.
AB  - Afrotheria is the clade of placental mammals that, together with Xenarthra,
      Euarchontoglires and Laurasiatheria, represents 1 of the 4 main recognized
      supraordinal eutherian clades. It reunites 6 orders of African origin:
      Proboscidea, Sirenia, Hyracoidea, Macroscelidea, Afrosoricida and Tubulidentata.
      The apparently unlikely relationship among such disparate morphological taxa and
      their possible basal position at the base of the eutherian phylogenetic tree led
      to a great deal of attention and research on the group. The use of biomolecular
      data was pivotal in Afrotheria studies, as they were the basis for the
      recognition of this clade. Although morphological evidence is still scarce, a
      plethora of molecular data firmly attests to the phylogenetic relationship among
      these mammals of African origin. Modern cytogenetic techniques also gave a
      significant contribution to the study of Afrotheria, revealing chromosome
      signatures for the group as a whole, as well as for some of its internal
      relationships. The associations of human chromosomes HSA1/19 and 5/21 were found
      to be chromosome signatures for the group and provided further support for
      Afrotheria. Additional chromosome synapomorphies were also identified linking
      elephants and manatees in Tethytheria (the associations HSA2/3, 3/13, 8/22, 18/19
      and the lack of HSA4/8) and elephant shrews with the aardvark (HSA2/8, 3/20 and
      10/17). Herein, we review the current knowledge on Afrotheria chromosomes and
      genome evolution. The already available data on the group suggests that further
      work on this apparently bizarre assemblage of mammals will provide important data
      to a better understanding on mammalian genome evolution.

PMID- 22868638
TI  - Fluorescence photoswitching and photoreversible two-way energy transfer in a
      photochrome-fluorophore dyad.
AB  - A thorough photophysical study of a photochrome-fluorophore dyad (3), combining a
      fluorescent laser dye (DCM-type, , Phi(1) = 0.27) and a photochromic diarylethene
      (2), obtained by click chemistry, is presented. In addition to photochromism, the
      open form (OF) of 2 exhibits fluorescence (Phi(-OF) = 0.016), whereas the closed
      form (CF) does not. Fluorescence is switched upon alternate UV/visible
      irradiation of 2. The emission band of 2-OF matches the absorption band of 1 (400
      550 nm), whereas the emission band of 1 overlaps the absorption band of 2-CF (550
      700 nm). Therefore, a photoreversible two-way excitation energy transfer (EET),
      controlled by the state of the photochromic moiety, is obtained in the dyad 3.
      Their efficiencies are quantified as Phi(EET)(OF->F) = 85% and as Phi(EET)(F->CF)
      ~ 100% from the comparison of emission and excitation spectra between 1, 2, and
      3. These results are fully compatible with the shortening of fluorescence
      lifetimes (from tau(-OF) = 70 ps and 170 ps essentially to tau(-OF) < 10 ps) and
      to the values of Forster radii determined for 3 (R(0)(OF -> F) = 29 A and R(0)(F 
      > CF) = 71 A), evidencing a Forster-type resonance energy transfer mechanism
      (FRET). An important outcome of this two-way FRET is the possibility to quench
      49% of the fluorescence in 3 at PSS upon UV irradiation, corresponding to the
      conversion extent of the photochromic reaction, which is different from 2
      (alpha(CF) = 91%). This is a clear example of a situation where the presence of
      FRET between the photochromic unit and the fluorophore affects noticeably the
      photochromic properties of the dyad molecule 3.

PMID- 22868639
TI  - Lemierre syndrome causing bilateral cavernous sinus thrombosis.
AB  - Lemierre syndrome is an uncommon septic thrombophlebitis of the veins of the head
      and the neck usually occurring after a severe oropharyngeal infection. Although
      subsequent septic emboli most commonly affect distant sites, such as the lungs
      and joints, the authors present a case of Lemierre syndrome causing bilateral
      cavernous sinus syndrome.

PMID- 22868640
TI  - Novel treatment for radiation optic neuropathy with intravenous bevacizumab.
AB  - Radiation optic neuropathy is a devastating form of vision loss that can occur
      months to years after radiation therapy for tumors and other lesions located in
      close proximity to the visual pathways. We present the case of a 24-year-old
      woman who underwent external beam radiation for treatment of a tectal pilocytic
      astrocytoma, and 5 years later she developed bilateral radiation optic neuropathy
      and radiation necrosis of the right temporal lobe. We opted to treat her with
      intravenous bevacizumab with 3 doses every 3 weeks, as well as dexamethasone and
      pentoxifylline. After the first infusion of bevacizumab, the patient noted
      improvement in vision and color vision, and a follow-up magnetic resonance
      imaging study showed that the previous enhancement of the optic nerves and chiasm
      was diminishing. Her vision improved dramatically and has remained stable over a
      3-year period.

PMID- 22868641
TI  - Towards high throughput metabolic flux analysis in plants.
AB  - Research on plant metabolism is currently experiencing the common use of various
      omics methods creating valuable information on the concentrations of the cell's
      constituents. However, little is known about in vivo reaction rates, which can be
      determined by Metabolic Flux Analysis (MFA), a combination of isotope labeling
      experiments and computer modeling of the metabolic network. Large-scale
      applications of this method so far have been hampered by tedious procedures of
      tissue culture, analytics, modeling and simulation. By streamlining the workflow
      of MFA, the throughput of the method could be significantly increased. We propose
      strategies for these improvements on various sub-steps which will move flux
      analysis to the medium-throughput range and closer to established methods such as
      metabolite profiling. Furthermore, this may enable novel applications of MFA, for
      example screening plant populations for traits related to the flux phenotype.

PMID- 22868643
TI  - High prevalence of extended-spectrum-beta-lactamase-producing Enterobacteriaceae
      in organic and conventional retail chicken meat, Germany.
AB  - OBJECTIVES: To determine the prevalence of extended-spectrum beta-lactamase
      (ESBL) production in Enterobacteriaceae in retail chicken meat in Germany.
      METHODS: A total of 399 chicken meat samples from nine supermarket chains, four
      organic food stores and one butcher's shop in two geographically distinct regions
      (Berlin and Greifswald) were screened for ESBL production using selective agar.
      Phenotypic ESBL isolates were tested for bla(TEM), bla(CTX-M) and bla(SHV) genes
      using PCR and DNA sequencing. Antibiotic coresistances were determined and strain
      typing was performed using PCR-based phylogenetic grouping and XbaI-PFGE.
      RESULTS: A total of 185 confirmed ESBL isolates were obtained from 175 samples
      (43.9%) from all tested sources. The majority of isolates were Escherichia coli
      producing ESBL types SHV-12 (n = 82), CTX-M-1 (n = 77) and TEM-52 (n = 16). No
      differences could be observed in the prevalence of ESBL producers between organic
      and conventional samples. 73.0% of the ESBL producers showed coresistance to
      tetracycline, 35.7% to co-trimoxazole and 7.6% to ciprofloxacin. Strain typing of
      selected E. coli isolates from Berlin revealed identical macrorestriction
      patterns for several isolates from samples taken from the same stores.
      CONCLUSIONS: This is the first comprehensive study from Germany showing a high
      prevalence of TEM-, CTX-M- and SHV-type ESBLs in Enterobacteriaceae isolated from
      retail chicken meat. The high rate of coresistance to different classes of
      antibiotics in the ESBL producers might reflect the common veterinary usage of
      these and related substances. There is an urgent need to further evaluate the
      role of poultry in the transmission of highly resistant ESBL-producing bacteria
      in humans.

PMID- 22868642
TI  - Sequential whole-body PET/MR scanner: concept, clinical use, and optimisation
      after two years in the clinic. The manufacturer's perspective.
AB  - PET and MRI are established clinical tools which provide complementary
      information, but clinical workflow limits widespread clinical application of both
      modalities in combination. The two modalities are usually situated in different
      hospital departments and operated and reported independently, and patients are
      referred for both scans, often consecutively. With the advent of PET/MR as a new
      hybrid imaging modality there is now a possibility of addressing these concerns.
      There are two different design philosophies for integrated PET/MR imaging
      positioning PET inside the MRI magnet or in tandem, similar to PET/CT. The
      Ingenuity TF PET/MR by Philips Healthcare is a sequential PET/MR tomograph
      combining state-of-the-art time-of-flight PET and high-field MRI with parallel
      transmission capabilities. In this review article we describe the technology
      implemented in the system, for example RF and magnetic shielding, MR-based
      attenuation correction, peculiarities in scatter correction, MR system
      optimisation, and the philosophy behind its design. Furthermore, we provide an
      overview of how the system has been used during the last two years, and
      expectations of how the use of PET/MR may continue in the years to come. On the
      basis of these observations and experiences we discuss the utility of the system,
      clinical workflow and acquisition times, and possible ways of optimization.

PMID- 22868645
TI  - Factors that affect selection of elite women's Sculling crews.
AB  - PURPOSE: There is no common theory on criteria to appropriately select crew
      rowers in pursuit of small performance gains. The purpose of this study was to
      establish whether anthropometry, rowing ergometry, or lower body strength were
      suitable criteria to identify differences between selected and nonselected
      sculling crews. METHOD: Twelve elite women performed a 2000-m ergometer time
      trial and a 5-repetition leg-press dynamometer test, were anthropometrically
      profiled, and participated in on-water national crew seat-racing trials. Log
      transformed data were analyzed to compare percent (+/- SD) and standardized
      differences in group means (ES; +/-90% confidence interval [CI]) between selected
      and nonselected oarswomen, with adjustments for body mass where appropriate.
      RESULTS: Selected crew boats were 4.60% +/- 0.02% faster and won by an average
      margin of 13.5 +/- 0.7 s over 1500 m. There were no differences between crews on
      average in height, arm span, seated height, body mass, or 8-site skinfold sum
      (body fat). Difference in 2000-m ergometer times were also trivial (ES = 0.2,
      90%CI = -0.6 to 1.1, P = .63); however, selected crews had moderately greater leg
      press strength (ES = 1.1, 90%CI = 0.3-1.9, P = .03). CONCLUSION: Selected
      oarswomen with comparable anthropometry and 2000-m ergometer ability had greater
      lower body strength. Coaches of elite oarswomen might consider leg strength as
      part of crew-selection criteria, given acceptable on-water boatmanship and
      attainment of 2000-m ergometer benchmarks.

PMID- 22868644
TI  - Epidemiology and echinocandin susceptibility of Candida parapsilosis sensu lato
      species isolated from bloodstream infections at a Spanish university hospital.
AB  - OBJECTIVES: The aims of this work were to study the epidemiological profiles,
      differences in echinocandin susceptibilities and clinical relevance of the
      Candida parapsilosis sensu lato species isolated from proven fungaemia cases at
      La Fe University Hospital of Valencia (Spain) from 1995 to 2007. RESULTS: The
      prevalence of these species was: C. parapsilosis sensu stricto, 74.4%; Candida
      orthopsilosis, 23.54%; and Candida metapsilosis, 2.05%. The incidence of the
      species complex as agents of fungaemia remained stationary until 2005 and doubled
      in 2006. The incidence of C. orthopsilosis showed an increasing trend during the
      study period, while C. parapsilosis sensu stricto incidence diminished. Also, an
      important epidemiological change was observed starting in 2004, when 86.5% of the
      C. parapsilosis sensu lato strains were found in adult patients, while before
      that year only 13.5% of the isolates were found in this population. CONCLUSIONS:
      Echinocandin drug susceptibility testing using the CLSI M27-A3 document showed a
      wide range of MIC values (0.015-4 mg/L), with micafungin being the most potent in
      vitro inhibitor followed by anidulafungin and caspofungin (MIC geometric mean of
      0.68, 0.74 and 0.87 mg/L, respectively). C. metapsilosis was the most susceptible
      species of the complex to anidulafungin and micafungin in vitro (MIC(50) for
      anidulafungin and micafungin: 0.06 mg/L), while there were no differences between
      C. parapsilosis sensu lato species when caspofungin MIC(50)s were compared
      (MIC(50) 1.00 mg/L). Differences in caspofungin in vitro susceptibility were
      observed between the different clinical service departments of La Fe Hospital.

PMID- 22868646
TI  - A fast approximate nearest neighbor search algorithm in the Hamming space.
AB  - A fast approximate nearest neighbor search algorithm for the (binary) Hamming
      space is proposed. The proposed Error Weighted Hashing (EWH) algorithm is up to
      20 times faster than the popular locality sensitive hashing (LSH) algorithm and
      works well even for large nearest neighbor distances where LSH fails. EWH
      significantly reduces the number of candidate nearest neighbors by weighing them
      based on the difference between their hash vectors. EWH can be used for
      multimedia retrieval and copy detection systems that are based on binary
      fingerprinting. On a fingerprint database with more than 1,000 videos, for a
      specific detection accuracy, we demonstrate that EWH is more than 10 times faster
      than LSH. For the same retrieval time, we show that EWH has a significantly
      better detection accuracy with a 15 times lower error rate.

PMID- 22868647
TI  - Comparative analysis and fusion of spatiotemporal information for footstep
      recognition.
AB  - Footstep recognition is a relatively new biometric which aims to discriminate
      people using walking characteristics extracted from floor-based sensors. This
      paper reports for the first time a comparative assessment of the spatiotemporal
      information contained in the footstep signals for person recognition. Experiments
      are carried out on the largest footstep database collected to date, with almost
      20,000 valid footstep signals and more than 120 people. Results show very similar
      performance for both spatial and temporal approaches (5 to 15 percent EER
      depending on the experimental setup), and a significant improvement is achieved
      for their fusion (2.5 to 10 percent EER). The assessment protocol is focused on
      the influence of the quantity of data used in the reference models, which serves
      to simulate conditions of different potential applications such as smart homes or
      security access scenarios.

PMID- 22868648
TI  - Spectral 6DOF registration of noisy 3D range data with partial overlap.
AB  - We present Spectral Registration with Multilayer Resampling (SRMR) as a 6 Degrees
      Of Freedom (DOF) registration method for noisy 3D data with partial overlap. The
      algorithm is based on decoupling 3D rotation from 3D translation by a
      corresponding resampling process of the spectral magnitude of a 3D Fast Fourier
      Transform (FFT) calculation on discretized 3D range data. The registration of all
      6DOF is then subsequently carried out with spectral registrations using Phase
      Only Matched Filtering (POMF). There are two main aspects for the fast and robust
      registration of Euler angles from spherical information in SRMR. First of all,
      there is the permanent use of phase matching. Second, based on the FFT on a
      discrete Cartesian grid, not only one spherical layer but also a complete stack
      of layers are processed in one step. Experiments are presented with challenging
      datasets with respect to interference and overlap. The results include the fast
      and robust registration of artificially transformed data for ground-truth
      comparison, scans from the Stanford Bunny dataset, high end 3D laser range finder
      (LRF) scans of a city center, and range data from a low-cost actuated LRF in a
      disaster response scenario.

PMID- 22868649
TI  - Incremental learning of 3D-DCT compact representations for robust visual
      tracking.
AB  - Visual tracking usually requires an object appearance model that is robust to
      changing illumination, pose, and other factors encountered in video. Many recent
      trackers utilize appearance samples in previous frames to form the bases upon
      which the object appearance model is built. This approach has the following
      limitations: 1) The bases are data driven, so they can be easily corrupted, and
      2) it is difficult to robustly update the bases in challenging situations. In
      this paper, we construct an appearance model using the 3D discrete cosine
      transform (3D-DCT). The 3D-DCT is based on a set of cosine basis functions which
      are determined by the dimensions of the 3D signal and thus independent of the
      input video data. In addition, the 3D-DCT can generate a compact energy spectrum
      whose high-frequency coefficients are sparse if the appearance samples are
      similar. By discarding these high-frequency coefficients, we simultaneously
      obtain a compact 3D-DCT-based object representation and a signal reconstruction
      based similarity measure (reflecting the information loss from signal
      reconstruction). To efficiently update the object representation, we propose an
      incremental 3D-DCT algorithm which decomposes the 3D-DCT into successive
      operations of the 2D discrete cosine transform (2D-DCT) and 1D discrete cosine
      transform (1D-DCT) on the input video data. As a result, the incremental 3D-DCT
      algorithm only needs to compute the 2D-DCT for newly added frames as well as the
      1D-DCT along the third dimension, which significantly reduces the computational
      complexity. Based on this incremental 3D-DCT algorithm, we design a
      discriminative criterion to evaluate the likelihood of a test sample belonging to
      the foreground object. We then embed the discriminative criterion into a particle
      filtering framework for object state inference over time. Experimental results
      demonstrate the effectiveness and robustness of the proposed tracker.

PMID- 22868650
TI  - Optimizing nondecomposable loss functions in structured prediction.
AB  - We develop an algorithm for structured prediction with nondecomposable
      performance measures. The algorithm learns parameters of Markov Random Fields
      (MRFs) and can be applied to multivariate performance measures. Examples include
      performance measures such as Fbeta score (natural language processing),
      intersection over union (object category segmentation), Precision/Recall at k
      (search engines), and ROC area (binary classifiers). We attack this optimization
      problem by approximating the loss function with a piecewise linear function. The
      loss augmented inference forms a Quadratic Program (QP), which we solve using LP
      relaxation. We apply this approach to two tasks: object class-specific
      segmentation and human action retrieval from videos. We show significant
      improvement over baseline approaches that either use simple loss functions or
      simple scoring functions on the PASCAL VOC and H3D Segmentation datasets, and a
      nursing home action recognition dataset.

PMID- 22868651
TI  - An automatic iris occlusion estimation method based on high-dimensional density
      estimation.
AB  - Iris masks play an important role in iris recognition. They indicate which part
      of the iris texture map is useful and which part is occluded or contaminated by
      noisy image artifacts such as eyelashes, eyelids, eyeglasses frames, and specular
      reflections. The accuracy of the iris mask is extremely important. The
      performance of the iris recognition system will decrease dramatically when the
      iris mask is inaccurate, even when the best recognition algorithm is used.
      Traditionally, people used the rule-based algorithms to estimate iris masks from
      iris images. However, the accuracy of the iris masks generated this way is
      questionable. In this work, we propose to use Figueiredo and Jain's Gaussian
      Mixture Models (FJ-GMMs) to model the underlying probabilistic distributions of
      both valid and invalid regions on iris images. We also explored possible features
      and found that Gabor Filter Bank (GFB) provides the most discriminative
      information for our goal. Finally, we applied Simulated Annealing (SA) technique
      to optimize the parameters of GFB in order to achieve the best recognition rate.
      Experimental results show that the masks generated by the proposed algorithm
      increase the iris recognition rate on both ICE2 and UBIRIS dataset, verifying the
      effectiveness and importance of our proposed method for iris occlusion
      estimation.

PMID- 22868652
TI  - Learning a confidence measure for optical flow.
AB  - We present a supervised learning-based method to estimate a per-pixel confidence
      for optical flow vectors. Regions of low texture and pixels close to occlusion
      boundaries are known to be difficult for optical flow algorithms. Using a
      spatiotemporal feature vector, we estimate if a flow algorithm is likely to fail
      in a given region. Our method is not restricted to any specific class of flow
      algorithm and does not make any scene specific assumptions. By automatically
      learning this confidence, we can combine the output of several computed flow
      fields from different algorithms to select the best performing algorithm per
      pixel. Our optical flow confidence measure allows one to achieve better overall
      results by discarding the most troublesome pixels. We illustrate the
      effectiveness of our method on four different optical flow algorithms over a
      variety of real and synthetic sequences. For algorithm selection, we achieve the
      top overall results on a large test set, and at times even surpass the results of
      the best algorithm among the candidates.

PMID- 22868653
TI  - Efficient optimization of performance measures by classifier adaptation.
AB  - In practical applications, machine learning algorithms are often needed to learn
      classifiers that optimize domain specific performance measures. Previously, the
      research has focused on learning the needed classifier in isolation, yet learning
      nonlinear classifier for nonlinear and nonsmooth performance measures is still
      hard. In this paper, rather than learning the needed classifier by optimizing
      specific performance measure directly, we circumvent this problem by proposing a
      novel two-step approach called CAPO, namely, to first train nonlinear auxiliary
      classifiers with existing learning methods and then to adapt auxiliary
      classifiers for specific performance measures. In the first step, auxiliary
      classifiers can be obtained efficiently by taking off-the-shelf learning
      algorithms. For the second step, we show that the classifier adaptation problem
      can be reduced to a quadratic program problem, which is similar to linear
      SVM(perf) and can be efficiently solved. By exploiting nonlinear auxiliary
      classifiers, CAPO can generate nonlinear classifier which optimizes a large
      variety of performance measures, including all the performance measures based on
      the contingency table and AUC, while keeping high computational efficiency.
      Empirical studies show that CAPO is effective and of high computational
      efficiency, and it is even more efficient than linear SVM(perf).

PMID- 22868654
TI  - Joint depth map and color consistency estimation for stereo images with different
      illuminations and cameras.
AB  - Abstract-In this paper, we propose a method that infers both accurate depth maps
      and color-consistent stereo images for radiometrically varying stereo images. In
      general, stereo matching and performing color consistency between stereo images
      are a chicken-and-egg problem since it is not a trivial task to simultaneously
      achieve both goals. Hence, we have developed an iterative framework in which
      these two processes can boost each other. First, we transform the input color
      images to log-chromaticity color space, from which a linear relationship can be
      established during constructing a joint pdf of transformed left and right color
      images. From this joint pdf, we can estimate a linear function that relates the
      corresponding pixels in stereo images. Based on this linear property, we present
      a new stereo matching cost by combining Mutual Information (MI), SIFT descriptor,
      and segment-based plane-fitting to robustly find correspondence for stereo image
      pairs which undergo radiometric variations. Meanwhile, we devise a Stereo Color
      Histogram Equalization (SCHE) method to produce color-consistent stereo image
      pairs, which conversely boost the disparity map estimation. Experimental results
      show that our method produces both accurate depth maps and color-consistent
      stereo images, even for stereo images with severe radiometric differences.

PMID- 22868655
TI  - Attentional WM is not necessarily specifically related with fluid intelligence:
      the case of smart children with ADHD symptoms.
AB  - Executive functions and, in particular, Attentional (active) Working Memory (WM)
      have been associated with fluid intelligence. The association contrasts with the
      hypothesis that children with ADHD exhibit problems with WM tasks requiring
      controlled attention and may have a good fluid intelligence. This paper examines
      whether children who are intelligent but present ADHD symptoms fail in
      attentional WM tasks. The latter result would be problematic for theories
      assuming the generality of a strict relationship between intelligence and WM. To
      study these issues, a battery of tests was administered to a group of 58 children
      who all displayed symptoms of ADHD. All children were between the age of 8 and 11
      years, and were described by their teachers as smart. Children were compared to a
      control group matched for age, schooling, and gender. The battery included a test
      of fluid intelligence (Raven's Coloured Matrices), and a series of visuospatial
      WM tasks. Results showed that children with ADHD were high in intelligence but
      significantly lower than the controls in WM tasks requiring high attentional
      control, whereas there was no difference in WM tasks requiring low attentional
      control. Furthermore, only high attentional control WM tasks were significantly
      related to Raven's performance in the control group, whereas all WM tasks were
      similarly related in the ADHD group. It is concluded that performance in high
      attentional control WM tasks may be related to fluid intelligence, but also to a
      specific control component that is independent of intelligence and is poor in
      children with ADHD.

PMID- 22868656
TI  - The effect of risedronate (17.5 mg/week) treatment on quality of life in Japanese
      women with osteoporosis: a prospective observational study.
AB  - A prospective observational study to test the effects of risedronate 17.5 mg/week
      treatment on quality of life (QOL) of 1,363 Japanese female patients with
      osteoporosis showed QOL improvement after 12 weeks of administration. Comorbid
      factors such as ischemic heart disease, hip osteoarthritis, and higher values of
      FRAX blunted the effects of QOL of the treatment. Few studies have investigated
      the effect of osteoporosis treatment on QOL in relationship to comorbid factors
      other than osteoporosis and fracture. Efficacy was determined by changes over
      time in EQ-5D at baseline, at 12 and 24 weeks, and at the final assessment.
      Factors affecting changes in EQ-5D were evaluated with a multivariate analysis.
      Safety was determined by assessing the incident rate of adverse events. The
      improvement of EQ-5D compared to baseline was observed as significant after 12
      weeks of treatment (p < 0.001). The greatest improvement was observed in the
      dimension of "pain/discomfort" by the multivariate analysis (p < 0.001). Factors
      affecting QOL improvement were FRAX value without BMD, age, glucocorticoid use,
      ischemic heart disease, hip osteoarthritis, and pain. The incidence rate of drug
      related adverse events was 4.72 % (95 % confidence interval 3.63-6.02 %).
      Risedronate at 17.5 mg/week improved the QOL in patients with osteoporosis among
      Japanese women, and comorbidity factors decreased the effects.

PMID- 22868658
TI  - Hepatitis: Global eradication of hepatitis B--feasible or fallacy?

PMID- 22868657
TI  - Effects of raloxifene on lipid and bone metabolism in postmenopausal women with
      type 2 diabetes.
AB  - Evidence suggests that bone quality is poorer and fracture risk is higher in
      patients with diabetes, even those with normal bone mineral density. The aim of
      this study was to determine the effects of raloxifene on lipid, bone, and glucose
      metabolism in postmenopausal women with type 2 diabetes. The study subjects (144
      postmenopausal women aged less than 80 years with type 2 diabetes) were randomly
      assigned into three groups: no medication, alfacalcidol 1 MUg/day, or raloxifene
      hydrochloride 60 mg/day. The primary endpoint was the change in LDL-C at 6
      months. Raloxifene significantly decreased the levels of bone metabolism markers
      NTX and BAP at 6 months in patients with diabetes. The primary endpoint, LDL-C at
      6 months, was significantly lower in the raloxifene group than in the other two
      groups. However, percent changes in HDL-C were not significantly different among
      the three groups. Although glucose metabolism was unaffected, homocysteine, a
      bone quality marker, was significantly decreased at 6 months in the raloxifene
      group. The percent improvement in LDL-C did not correlate with percent
      improvement in any bone metabolism or bone quality markers. Raloxifene, unlike
      estrogen, improved LDL-C and decreased homocysteine, indicating that raloxifene
      can potentially improve LDL-C as well as bone quality in postmenopausal women
      with type 2 diabetes.

PMID- 22868659
TI  - Ulcerative colitis: Paediatric ulcerative colitis--can we predict
      proctocolectomy?

PMID- 22868660
TI  - Inflammation: Colitis, microbiota and malnutrition.

PMID- 22868661
TI  - Dyspepsia: Psychological factors in functional dyspepsia--keeping an open mind.

PMID- 22868662
TI  - A system-level transcriptomic analysis of schizophrenia using postmortem brain
      tissue samples.
AB  - CONTEXT Schizophrenia is a common, highly heritable, neurodevelopmental mental
      illness, characterized by genetic heterogeneity. OBJECTIVE To identify
      abnormalities in the transcriptome organization among older persons with
      schizophrenia and controls. DESIGN Weighted gene coexpression network analysis
      based on microarray transcriptomic profiling. SETTING Research hospital. PATIENTS
      Postmortem brain tissue samples from 4 different cerebrocortical regions (the
      dorsolateral prefrontal cortex, the middle temporal area, the temporopolar area,
      and the anterior cingulate cortex) from 21 persons with schizophrenia and 19
      controls. MAIN OUTCOME MEASURES Results from gene expression microarray analysis,
      from analysis of coexpression networks, and from module eigengene, module
      preservation, and enrichment analysis of schizophrenia-related genetic variants.
      RESULTS The oligodendrocyte, microglial, mitochondrial, and neuronal (GABAergic
      and glutamatergic) modules were associated with disease status. Enrichment
      analysis of genome-wide association studies in schizophrenia and other illnesses
      demonstrated that the neuronal (GABAergic and glutamatergic) and oligodendrocyte
      modules are enriched for genetically associated variants, whereas the microglial
      and mitochondrial modules are not, providing independent support for more direct
      involvement of these gene expression networks in schizophrenia. Interregional
      coexpression network analysis showed that the gene expression patterns that
      typically differentiate the frontal, temporal, and cingulate cortices in controls
      diminish significantly in persons with schizophrenia. CONCLUSIONS These results
      support the existence of convergent molecular abnormalities in schizophrenia,
      providing a molecular neuropathological basis for the disease.

PMID- 22868663
TI  - Physical Activity and Mortality in Individuals With Diabetes Mellitus: A
      Prospective Study and Meta-analysis.
AB  - BACKGROUND Physical activity (PA) is considered a cornerstone of diabetes
      mellitus management to prevent complications, but conclusive evidence is lacking.
      METHODS This prospective cohort study and meta-analysis of existing studies
      investigated the association between PA and mortality in individuals with
      diabetes. In the EPIC study (European Prospective Investigation Into Cancer and
      Nutrition), a cohort was defined of 5859 individuals with diabetes at baseline.
      Associations of leisure-time and total PA and walking with cardiovascular disease
      (CVD) and total mortality were studied using multivariable Cox proportional
      hazards regression models. Fixed- and random-effects meta-analyses of prospective
      studies published up to December 2010 were pooled with inverse variance
      weighting. RESULTS In the prospective analysis, total PA was associated with
      lower risk of CVD and total mortality. Compared with physically inactive persons,
      the lowest mortality risk was observed in moderately active persons: hazard
      ratios were 0.62 (95% CI, 0.49-0.78) for total mortality and 0.51 (95% CI, 0.32
      0.81) for CVD mortality. Leisure-time PA was associated with lower total
      mortality risk, and walking was associated with lower CVD mortality risk. In the
      meta-analysis, the pooled random-effects hazard ratio from 5 studies for high vs
      low total PA and all-cause mortality was 0.60 (95% CI, 0.49-0.73). CONCLUSIONS
      Higher levels of PA were associated with lower mortality risk in individuals with
      diabetes. Even those undertaking moderate amounts of activity were at appreciably
      lower risk for early death compared with inactive persons. These findings provide
      empirical evidence supporting the widely shared view that persons with diabetes
      should engage in regular PA.

PMID- 22868665
TI  - The evolutionary success of sex. Science & Society Series on Sex and Science.

PMID- 22868667
TI  - Cell-nonautonomous control of the UPR.

PMID- 22868668
TI  - Plants are intelligent too.

PMID- 22868664
TI  - Activation of B cells by non-canonical helper signals.
AB  - Cognate interaction between T and B lymphocytes of the adaptive immune system is
      essential for the production of high-affinity antibodies against microbes, and
      for the establishment of long-term immunological memory. Growing evidence shows
      that--in addition to presenting antigens to T and B cells--macrophages, dendritic
      cells and other cells of the innate immune system provide activating signals to B
      cells, as well as survival signals to antibody-secreting plasma cells. Here, we
      discuss how these innate immune cells contribute to the induction of highly
      diversified and temporally sustained antibody responses, both systemically and at
      mucosal sites of antigen entry.

PMID- 22868669
TI  - Reply from Authors re: Riccardo Bartoletti, Tommaso Cai. Prostate Biopsies Should
      Be Performed According to a Standard of Care. Eur Urol 2013;63:528-9.

PMID- 22868670
TI  - ICUD-EAU International Consultation on Bladder Cancer 2012: Recommendations on
      bladder cancer-progress in a cancer that lacks the limelight.

PMID- 22868671
TI  - Do infants die of sudden infant death syndrome (SIDS) with long QT syndrome
      (LQTS) or from LQTS?

PMID- 22868672
TI  - Rhythm and conduction analysis of patients with acute rheumatic fever.
AB  - Various rhythm and conduction abnormalities can develop in acute rheumatic fever.
      This study investigated rhythm and conduction abnormalities in children with
      acute rheumatic fever using a standard 12-lead electrocardiogram and 24-h rhythm
      Holter recordings. This multicenter retrospective study, performed between August
      2011 and March 2012, enrolled 73 consecutive children with acute rheumatic fever.
      Standard electrocardiography was used to measure PR and corrected QT intervals.
      Holter recordings were evaluated for all the patients, and 52 of the patients
      (71.2 %) had carditis that was either isolated or together with other major
      criteria. A positive correlation was detected between carditis and the mean PR
      interval on standard electrocardiography, but this was not significant (p >
      0.05). Standard electrocardiography showed a significant positive correlation
      between PR and corrected QT intervals (p = 0.03; r = 0.55). Standard
      electrocardiography showed only three patients (4.2 %) with premature
      contractions, whereas 24-h electrocardiography showed 26 patients (35.6 %) with
      premature contractions. Carditis was positively correlated with premature
      contractions (p < 0.01; r = 0.57). One patient with junctional rhythm and one
      patient with left bundle block were detected by standard electrocardiography.
      Whereas some patients with carditis exhibited no arrhythmic evidence on standard
      electrocardiograms, complete atrioventricular block, supraventricular
      tachycardia, and Mobitz type 1 block were observed on 24-h Holter recordings. A
      positive correlation also was observed between the presence of premature
      contractions and serum levels of acute-phase reactants (p = 0.03; r = 0.62).
      These findings led to the conclusion that rhythm and conduction disorders in
      acute rheumatic fever are more common than previously thought.

PMID- 22868673
TI  - Use of the Multispecies Freshwater Biomonitor to assess behavioral changes of
      Poecilia reticulata (Cyprinodontiformes: Poeciliidae) and Macrobrachium
      lanchesteri (Decapoda: Palaemonidae) in response to acid mine drainage:
      laboratory exposure.
AB  - The behavioral responses of guppy Poecilia reticulata (Poeciliidae) and prawn
      Macrobrachium lanchesteri (Palaemonidae) individuals exposed to acid mine
      drainage (AMD) were monitored online in the laboratory with a Multispecies
      Freshwater BiomonitorTM (MFB). These responses were compared to those to
      reference water acidified to the respective pH values (ACID). Test animals in the
      juvenile stage were used for both species and were exposed to AMD and ACID for 24
      hours. The stress behaviors of both test animals consisted mainly of decreased
      activity in AMD and increased activity in ACID, indicating that the metals in the
      AMD played a role as a stress factor in addition to pH. The locomotor activity
      levels of guppies and prawns for the ACID treatment were higher than the
      locomotor activity levels for the AMD treatment with increasing pH value. For
      guppies, significant differences were observed when specimens were exposed to AMD
      and ACID at pH 5.0 and 6.0; the percentage activities were only 16% and 12%,
      respectively, for AMD treatment, whereas for ACID treatment, the percentage
      activities were 35% and 40%, respectively, similar to the value of 36% for the
      controls. Similar trends were also observed for prawns, for which the percentage
      activities were only 6% and 4%, respectively, for AMD treatment, whereas for ACID
      treatment, the percentage activities were 31% and 38%, respectively, compared to
      44% in the controls. This study showed that both species are suitable for use as
      indicators for ecotoxicity testing with the MFB.

PMID- 22868674
TI  - Studying the effects of stereo, head tracking, and field of regard on a small
      scale spatial judgment task.
AB  - Spatial judgments are important for many real-world tasks in engineering and
      scientific visualization. While existing research provides evidence that higher
      levels of display and interaction fidelity in virtual reality systems offer
      advantages for spatial understanding, few investigations have focused on small
      scale spatial judgments or employed experimental tasks similar to those used in
      real-world applications. After an earlier study that considered a broad analysis
      of various spatial understanding tasks, we present the results of a follow-up
      study focusing on small-scale spatial judgments. In this research, we
      independently controlled field of regard, stereoscopy, and head-tracked rendering
      to study their effects on the performance of a task involving precise spatial
      inspections of complex 3D structures. Measuring time and errors, we asked
      participants to distinguish between structural gaps and intersections between
      components of 3D models designed to be similar to real underground cave systems.
      The overall results suggest that the addition of the higher fidelity system
      features support performance improvements in making small-scale spatial
      judgments. Through analyses of the effects of individual system components, the
      experiment shows that participants made significantly fewer errors with either an
      increased field of regard or with the addition of head-tracked rendering. The
      results also indicate that participants performed significantly faster when the
      system provided the combination of stereo and head-tracked rendering.

PMID- 22868675
TI  - Metabolome 2.0: quantitative genetics and network biology of metabolic
      phenotypes.
AB  - The characterization of the metabolome has rapidly evolved over two decades, from
      early developments in analytical chemistry to systems biology. Metabolites and
      small molecules are not independent; they are organized in biochemical pathways
      and in a wider metabolic network, which is itself dependent on various genetic
      and signaling networks for its regulation. Recent advances in genomics,
      transcriptomics, proteomics and metabolomics have been matched by the development
      of publicly available repositories, which have helped shaping a new generation of
      integrative studies using metabolite measurements in molecular epidemiology and
      genetic studies. Although the environment influences metabolism, the
      identification of the genetic determinants of metabolic phenotypes (metabotypes)
      was made possible by the development of metabotype quantitative trait locus
      (mQTL) mapping and metabolomic genome-wide association studies (mGWAS) in a
      rigorous statistical genetics framework, deriving associations between metabolite
      concentrations and genetic polymorphisms. However, given the complexity of the
      biomolecular events involved in the regulation of metabolic patterns, alternative
      network biology approaches have also been recently introduced, such as integrated
      metabolome and interactome mapping (iMIM). This unprecedented convergence of
      metabolic biochemistry, quantitative genetics and network biology already has had
      a strong impact on the role of the metabolome in biomedical sciences, and this
      review gives a foretaste of its anticipated successes in eventually delivering
      personalized medicine.

PMID- 22868677
TI  - A characterization of the set of species trees that produce anomalous ranked gene
      trees.
AB  - Ranked gene trees, which consider both the gene tree topology and the sequence in
      which gene lineages separate, can potentially provide a new source of information
      for use in modeling genealogies and performing inference of species trees.
      Recently,we have calculated the probability distribution of ranked gene trees
      under the standard multispecies coalescent model for the evolution of gene
      lineages along the branches of a fixed species tree, demonstrating the existence
      of anomalous ranked gene trees (ARGTs), in which a ranked gene tree that does not
      match the ranked species tree can have greater probability under the model than
      the matching ranked gene tree. Here, we fully characterize the set of unranked
      species tree topologies that give rise to ARGTs, showing that this set contains
      all species tree topologies with five or more taxa, with the exceptions of
      caterpillars and pseudocaterpillars. The results have implications for the use of
      ranked gene trees in phylogenetic inference.

PMID- 22868676
TI  - Physical exercise and pancreatic islets: acute and chronic actions on insulin
      secretion.
AB  - Diabetes mellitus (DM) is a great public health problem, which attacks part of
      the world population, being characterized by an imbalance in body glucose
      homeostasis. Physical exercise is pointed as a protective agent and is also
      recommended to people with DM. As pancreatic islets present an important role in
      glucose homeostasis, we aim to study the role of physical exercise (chronic
      adaptations and acute responses) in pancreatic islets functionality in Wistar
      male rats. First, animals were divided into two groups: sedentary (S) and aerobic
      trained (T). At the end of 8 weeks, half of them (S and T) were submitted to an
      acute exercise session (exercise until exhaustion), being subdivided as acute
      sedentary (AS) and acute trained (AT). After the experimental period,
      periepididymal, retroperitoneal and subcutaneous fat pads, blood, soleus muscle
      and pancreatic islets were collected and prepared for further analysis. From the
      pancreatic islets, total insulin content, insulin secretion stimulated by
      glucose, leucine, arginine and carbachol were analyzed. Our results pointed that
      body adiposity and glucose homeostasis improved with chronic physical exercise.
      In addition, total insulin content was reduced in group AT, insulin secretion
      stimulated by glucose was reduced in trained groups (T and AT) and insulin
      secretion stimulated by carbachol was increased in group AT. There were no
      significant differences in insulin secretion stimulated by arginine and leucine.
      We identified a possible modulating action on insulin secretion, probably related
      to the association of chronic adaptation with an acute response on cholinergic
      activity in pancreatic islets.

PMID- 22868678
TI  - Automatic identification and classification of noun argument structures in
      biomedical literature.
AB  - The accelerating increase in the biomedical literature makes keeping up with
      recent advances challenging for researchers thus making automatic extraction and
      discovery of knowledge from this vast literature a necessity. Building such
      systems requires automatic detection of lexico-semantic event structures governed
      by the syntactic and semantic constraints of human languages in sentences of
      biomedical texts. The lexico-semantic event structures in sentences are centered
      around the predicates and most semantic role labeling (SRL) approaches focus only
      on the arguments of verb predicates and neglect argument taking nouns which also
      convey information in a sentence. In this article, a noun argument structure
      (NAS) annotated corpus named BioNom and a SRL system to identify and classify
      these structures is introduced. Also, a genetic algorithm-based feature selection
      (GAFS) method is introduced and global inference is applied to significantly
      improve the performance of the NAS Bio SRL system.

PMID- 22868679
TI  - Biomarker identification and cancer classification based on microarray data using
      Laplace naive Bayes model with mean shrinkage.
AB  - Biomarker identification and cancer classification are two closely related
      problems. In gene expression data sets, the correlation between genes can be high
      when they share the same biological pathway. Moreover, the gene expression data
      sets may contain outliers due to either chemical or electrical reasons. A good
      gene selection method should take group effects into account and be robust to
      outliers. In this paper, we propose a Laplace naive Bayes model with mean
      shrinkage (LNB-MS). The Laplace distribution instead of the normal distribution
      is used as the conditional distribution of the samples for the reasons that it is
      less sensitive to outliers and has been applied in many fields. The key technique
      is the L1 penalty imposed on the mean of each class to achieve automatic feature
      selection. The objective function of the proposed model is a piecewise linear
      function with respect to the mean of each class, of which the optimal value can
      be evaluated at the breakpoints simply. An efficient algorithm is designed to
      estimate the parameters in the model. A new strategy that uses the number of
      selected features to control the regularization parameter is introduced.
      Experimental results on simulated data sets and 17 publicly available cancer data
      sets attest to the accuracy, sparsity, efficiency, and robustness of the proposed
      algorithm. Many biomarkers identified with our method have been verified in
      biochemical or biomedical research. The analysis of biological and functional
      correlation of the genes based on Gene Ontology (GO) terms shows that the
      proposed method guarantees the selection of highly correlated genes
      simultaneously

PMID- 22868680
TI  - SC(3): Triple spectral clustering-based consensus clustering framework for class
      discovery from cancer gene expression profiles.
AB  - In order to perform successful diagnosis and treatment of cancer, discovering,
      and classifying cancer types correctly is essential. One of the challenging
      properties of class discovery from cancer data sets is that cancer gene
      expression profiles not only include a large number of genes, but also contains a
      lot of noisy genes. In order to reduce the effect of noisy genes in cancer gene
      expression profiles, we propose two new consensus clustering frameworks, named as
      triple spectral clustering-based consensus clustering (SC3) and double spectral
      clustering-based consensus clustering (SC2Ncut) in this paper, for cancer
      discovery from gene expression profiles. SC3 integrates the spectral clustering
      (SC) algorithm multiple times into the ensemble framework to process gene
      expression profiles. Specifically, spectral clustering is applied to perform
      clustering on the gene dimension and the cancer sample dimension, and also used
      as the consensus function to partition the consensus matrix constructed from
      multiple clustering solutions.Compared with SC3, SC2Ncut adopts the normalized
      cut algorithm, instead of spectral clustering, as the consensus
      function.Experiments on both synthetic data sets and real cancer gene expression
      profiles illustrate that the proposed approaches not only achieve good
      performance on gene expression profiles, but also outperforms most of the
      existing approaches in the process of class discovery from these profiles.

PMID- 22868681
TI  - Multiparameter spectral representation of noise-induced competence in Bacillus
      subtilis.
AB  - In this work, the problem of representing a stochastic forward model output with
      respect to a large number of input parameters is considered. The methodology is
      applied to a stochastic reaction network of competence dynamics in Bacillus
      subtilis bacterium. In particular, the dependence of the competence state on rate
      constants of underlying reactions is investigated. We base our methodology on
      Polynomial Chaos (PC) spectral expansions that allow effective propagation of
      input parameter uncertainties to outputs of interest. Given a number of forward
      model training runs at sampled input parameter values, the PC modes are estimated
      using a Bayesian framework. As an outcome, these PC modes are described with
      posterior probability distributions. The resulting expansion can be regarded as
      an uncertain response function and can further be used as a computationally
      inexpensive surrogate instead of the original reaction model for subsequent
      analyses such as calibration or optimization studies. Furthermore, the
      methodology is enhanced with a classification-based mixture PC formulation that
      overcomes the difficulties associated with representing potentially nonsmooth
      input-output relationships. Finally, the global sensitivity analysis based on the
      multiparameter spectral representation of an observable of interest provides
      biological insight and reveals the most important reactions and their couplings
      for the competence dynamics

PMID- 22868682
TI  - Sequence-based prediction of DNA-binding residues in proteins with conservation
      and correlation information.
AB  - The recognition of DNA-binding residues in proteins is critical to our
      understanding of the mechanisms of DNA-protein interactions, gene expression, and
      for guiding drug design. Therefore, a prediction method DNABR (DNA Binding
      Residues) is proposed for predicting DNA-binding residues in protein sequences
      using the random forest (RF) classifier with sequence-based features. Two types
      of novel sequence features are proposed in this study, which reflect the
      information about the conservation of physicochemical properties of the amino
      acids, and the correlation of amino acids between different sequence positions in
      terms of physicochemical properties. The first type of feature uses the
      evolutionary information combined with the conservation of physicochemical
      properties of the amino acids while the second reflects the dependency effect of
      amino acids with regards to polarity charge and hydrophobic properties in the
      protein sequences. Those two features and an orthogonal binary vector which
      reflect the characteristics of 20 types of amino acids are used to build the
      DNABR, a model to predict DNA-binding residues in proteins. The DNABR model
      achieves a value of 0.6586 for Matthew's correlation coefficient (MCC) and 93.04
      percent overall accuracy (ACC) with a68.47 percent sensitivity (SE) and 98.16
      percent specificity (SP), respectively. The comparisons with each feature
      demonstrate that these two novel features contribute most to the improvement in
      predictive ability. Furthermore, performance comparisons with other approaches
      clearly show that DNABR has an excellent prediction performance for detecting
      binding residues in putative DNA-binding protein. The DNABR web-server system is
      freely available at http://www.cbi.seu.edu.cn/DNABR/.

PMID- 22868683
TI  - Probabilistic arithmetic automata and their applications.
AB  - We present a comprehensive review on probabilistic arithmetic automata (PAAs), a
      general model to describe chains of operations whose operands depend on chance,
      along with two algorithms to numerically compute the distribution of the results
      of such probabilistic calculations. PAAs provide a unifying framework to approach
      many problems arising in computational biology and elsewhere. We present five
      different applications, namely 1) pattern matching statistics on random texts,
      including the computation of the distribution of occurrence counts, waiting
      times, and clump sizes under hidden Markov background models; 2) exact analysis
      of window-based pattern matching algorithms; 3) sensitivity of filtration seeds
      used to detect candidate sequence alignments; 4) length and mass statistics of
      peptide fragments resulting from enzymatic cleavage reactions; and 5) read length
      statistics of 454 and IonTorrent sequencing reads. The diversity of these
      applications indicates the flexibility and unifying character of the presented
      framework. While the construction of a PAA depends on the particular application,
      we single out a frequently applicable construction method: We introduce
      deterministic arithmetic automata (DAAs) to model deterministic calculations on
      sequences, and demonstrate how to construct a PAA from a given DAA and a finite
      memory random text model. This procedure is used for all five discussed
      applications and greatly simplifies the construction of PAAs. Implementations are
      available as part of the MoSDi package. Its application programming interface
      facilitates the rapid development of new applications based on the PAA framework.

PMID- 22868684
TI  - Efficacy and safety of a novel K-agonist for managing intractable pruritus in
      dialysis patients.
AB  - BACKGROUND: Our previous placebo-controlled, prospective, double-blind study
      demonstrated that a new opioid K-receptor agonist, nalfurafine hydrochloride,
      effectively reduced treatment-resistant pruritus in 337 hemodialysis patients.
      Thus, we designed this study to evaluate prospectively the efficacy, safety,
      addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.
      METHODS: This open-label study examined the effects and adverse drug reactions
      (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 ug/day) in
      211 hemodialysis patients with a treatment-resistant itch. RESULTS: Of 211
      patients, 145 completed the study as scheduled. The mean pruritus value assessed
      by the visual analogue scale was 75.2 mm during the pre-observation period, which
      decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively,
      indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%).
      Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and
      increased blood prolactin (3.3%), similar to previous reports. Regarding
      addiction liability, it appeared unlikely that nalfurafine hydrochloride was
      abused. After the start of treatment, plasma drug levels reached a steady state
      in week 2 with no apparent tendency of systemic accumulation. CONCLUSIONS:
      Nalfurafine hydrochloride, orally administered at 5 ug/day for 52 weeks to
      hemodialysis patients, produced a long-term suppression of pruritus without
      significant safety problems.

PMID- 22868685
TI  - Annular pancreas: a rare cause of upper gastrointestinal bleeding in a child.

PMID- 22868686
TI  - DGUOK-related mitochondrial DNA depletion syndrome in a child with an early
      diagnosis of glycogen storage disease.

PMID- 22868689
TI  - High efficiency hybrid solar cells using post-deposition ligand exchange by
      monothiols.
AB  - High-performance hybrid solar cells (HSCs) based on P3HT : CdSe QD blends are
      achieved through post-deposition ligand exchange by n-butanethiol (n-BT) with a
      high power conversion efficiency of 3.09%. The mechanism by which n-BT modifies
      the surface structures of CdSe QDs and thus improves the HSCs performance is
      investigated.

PMID- 22868688
TI  - Neuroprotective effects of granulocyte colony-stimulating factor on ischemia
      reperfusion injury of the retina.
AB  - PURPOSE: It has been reported that granulocyte colony-stimulating factor (G-CSF)
      provides neuroprotection in models in which neuronal cell death is induced. This
      research was designed to investigate the effects of G-CSF on neurodegeneration of
      the inner retinal layer in a rat model of ischemic reperfusion (I/R) injury.
      MATERIALS AND METHODS: Retinal ischemia was induced by increasing the intraocular
      pressure to 110 mm Hg for 45 min in the left eyes of the rats. A sham operation
      was carried out on the right eyes. G-CSF (100 ug/kg/day in 0.3 ml saline) or the
      same volume of saline was intraperitoneally injected just before the operation
      and continued for 4 consecutive days (a total of 5 consecutive days).
      Morphological examinations, including the terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL) assay, were performed 7 days after I/R induction.
      The expression of phosphorylated AKT in the retina was examined by Western blot
      analysis and immunohistochemistry. RESULTS: Cell loss in the ganglion cell layer
      was more significantly reduced in the I/R-induced eyes of the G-CSF-injected rats
      than in the I/R-induced eyes of the saline-injected rats (20.3 vs. 6.6%). The
      inner retinal thickness ratios, such as the inner plexiform layer to the inner
      limiting membrane/outer nuclear layer and the inner nuclear layer/outer nuclear
      layer, were significantly better preserved in the I/R-induced eyes of the G-CSF
      injected rats than in the I/R-induced eyes of the saline-injected rats. TUNEL
      assays showed fewer apoptotic cells in the retinal sections of the I/R-induced
      eyes of the G-CSF-injected rats. The phosphorylation of AKT (p-AKT/AKT) was
      upregulated in the retinas of the I/R-induced eyes of the G-CSF-injected rats.
      CONCLUSION: Our results demonstrated that systemic injection of G-CSF can protect
      retinal ganglion cells and inner retinal layers from I/R injury. The effects
      could be associated with the activation of AKT.

PMID- 22868690
TI  - Experiences with treprostinil in the treatment of pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a chronic condition of elevated
      pulmonary arterial pressures with associated increases in pulmonary vascular
      resistance leading to right ventricular failure, which was almost uniformly fatal
      prior to the introduction of pulmonary hypertension specific therapy. Systemic
      prostacyclin analogs are the first PAH-specific therapies to be made available
      and are typically recommended as first-line therapy for subjects with severe
      disease. Treprostinil is a newer prostacyclin analog similar to epoprostenol in
      its mechanism of action and relative efficacy with the advantage of a longer half
      life in human serum and room temperature stability. It is unique in that it is
      available in multiple formulations for alternative routes of delivery, including
      subcutaneous, intravenous and inhalational routes. Additionally, oral
      treprostinil is currently under investigation. Both subcutaneous and intravenous
      forms of treprostinil have demonstrated efficacy in short-term clinical trials
      and are currently approved for use in subjects with PAH and New York Heart
      Association functional class (NYHA FC) II-IV symptoms in the USA and for subjects
      with NYHA FC III and IV in Europe. Inhaled treprostinil has also demonstrated
      efficacy in short-term clinical trials primarily as add-on therapy and is
      currently approved for use in subjects with PAH and NYHA FC III-IV symptoms in
      the USA and Europe. The different formulations of treprostinil have significantly
      increased the treatment options and opportunities for treatment of patients with
      PAH.

PMID- 22868691
TI  - A prospective study of weight training and risk of type 2 diabetes mellitus in
      men.
AB  - BACKGROUND The role of weight training in the primary prevention of type 2
      diabetes mellitus (T2DM) is largely unknown. METHODS To examine the association
      of weight training with risk of T2DM in US men and to assess the influence of
      combining weight training and aerobic exercise, we performed a prospective cohort
      study of 32 002 men from the Health Professionals Follow-up Study observed from
      1990 to 2008. Weekly time spent on weight training and aerobic exercise
      (including brisk walking, jogging, running, bicycling, swimming, tennis, squash,
      and calisthenics/rowing) was obtained from questionnaires at baseline and
      biennially during follow-up. RESULTS During 508 332 person-years of follow-up (18
      years), we documented 2278 new cases of T2DM. In multivariable-adjusted models,
      we observed a dose-response relationship between an increasing amount of time
      spent on weight training or aerobic exercise and lower risk of T2DM (P < .001 for
      trend). Engaging in weight training or aerobic exercise for at least 150 minutes
      per week was independently associated with a lower risk of T2DM of 34% (95% CI,
      7%-54%) and 52% (95% CI, 45%-58%), respectively. Men who engaged in aerobic
      exercise and weight training for at least 150 minutes per week had the greatest
      reduction in T2DM risk (59%; 95% CI, 39%-73%). CONCLUSIONS Weight training was
      associated with a significantly lower risk of T2DM, independent of aerobic
      exercise. Combined weight training and aerobic exercise conferred a greater
      benefit.

PMID- 22868693
TI  - Cardiac cystic echinococcosis: a long-term follow-up case report.

PMID- 22868696
TI  - Knowledge-based systems: contrasting realities and expectations and possible ways
      forward.

PMID- 22868694
TI  - Transvenous ICD lead malposition in the left ventricle: long-term follow-up.

PMID- 22868697
TI  - Intelligent data analysis for knowledge discovery, patient monitoring and quality
      assessment.
AB  - OBJECTIVE: To introduce the focus theme of Methods of Information in Medicine on
      Intelligent Data Analysis for Knowledge Discovery, Patient Monitoring and Quality
      Assessment. METHODS: Based on two workshops on Intelligent Data Analysis in
      bioMedicine (IDAMAP) held in Washington, DC, USA (2010) and Bled, Slovenia
      (2011), six authors were invited to write full papers for the focus theme. Each
      paper was throughly reviewed by anonymous referees and revised one or more times
      by the authors. RESULTS: The selected papers cover four ongoing and emerging
      topics in Intelligent Data Analysis (IDA), being i) systems biology and metabolic
      pathway modelling; ii) gene expression data modelling; iii) signal processing
      from in-home monitoring systems; and iv) quality of care assessment. Each of
      these topics is discussed in detail to introduce the papers to the reader.
      CONCLUSION: The development and application of IDA methods in biomedicine is an
      active area of research which continues to blend with other subfields of medical
      informatics. As data become increasingly ubiquitous in the biomedical domain, the
      demand for fast, smart and flexible data analysis methods is undiminished.

PMID- 22868698
TI  - A case of intrauterine gastric perforation in congenital diaphragmatic hernia.

PMID- 22868699
TI  - Treatment of bilateral simultaneous subtrochanteric femur fractures with proximal
      femoral nail antirotation (PFNA) in a patient with osteopetrosis: case report and
      review of the literature.

PMID- 22868700
TI  - Bipolar hemiarthroplasty compared with internal fixation for unstable
      intertrochanteric fractures in elderly patients.
AB  - BACKGROUND: The optimal treatment for unstable intertrochanteric fractures in
      elderly patients remains controversial. We aimed to compare internal fixation and
      bipolar hemiarthroplasty for the treatment of unstable intertrochanteric
      fractures in elderly patients. METHODS: 124 patients aged over 70 years were
      enrolled into this study (64 internal fixations, 60 bipolar hemiarthroplasties).
      Patients were followed for two years, and had a clinical, radiological, and
      functional review at three, six, and twelve months as well as two years. RESULTS:
      In the internal fixation group, the fracture reduction and internal fixation were
      regarded as satisfactory in 44 cases and unsatisfactory in 20 cases. Five
      patients in the internal fixation group (two with satisfactory results and three
      with unsatisfactory results) and three patients in the arthroplasty group died
      before the final two-year follow-up. Five patients in the internal fixation group
      who had unsatisfactory results suffered complications. At 24 months post
      operation, patients who were treated satisfactorily with internal fixation had
      higher Harris scores, less pain, and better walking ability than those treated
      with hemiarthroplasty and unsatisfactory internal fixation. CONCLUSIONS: Internal
      fixation with good reduction and fixation quality should be the preferred
      therapeutic method for elderly unstable intertrochanteric fractures, even when
      severe osteoporosis is present.

PMID- 22868701
TI  - Distal femoral osteotomy for valgus arthritic knees.
AB  - BACKGROUND: Patients with genu valgum and isolated osteoarthritis of the lateral
      compartment are candidates for distal femoral varus osteotomy. Opening wedge
      osteotomy is a precise method to realign the knee axis with good short to midterm
      results. The aim of this study was to evaluate the outcome of patients who have
      had opening wedge distal femoral varus osteotomy utilizing the Puddu plate
      (Arthrex, Naples, FL, USA) fixation. METHODS: The study included 6 patients (7
      knees) followed for an average of 6.5 +/- 1.5 years after distal femoral varus
      osteotomy with Puddu fixation and iliac crest allograft. Clinical outcome was
      assessed by the Oxford Knee Score and subjective satisfaction rating. Pre- and
      postoperative radiographs were evaluated for tibiofemoral angle, Insall-Salvati
      index and Kellgren-Lawrence Grading Scale for osteoarthritis. RESULTS: The mean
      age at surgery was 46.7 +/- 10.7 years. The mean body mass index at surgery was
      29.6 +/- 5.6 kg/m(2). Overall at the last follow-up the mean Oxford Knee Score
      improved from 13.1 +/- 8.6 to 26 +/- 12.5. The average subjective satisfaction
      rate at the last follow-up was 6.6 +/- 2.8. The measured tibiofemoral angle was
      corrected by an average of 11.9 degrees . There was no worsening of arthritic
      changes in comparison to the preoperational radiographs. All radiographs showed
      full incorporation of the bone grafts, and there were no hardware failures. At
      the end of this study none of the patients required additional surgery, and none
      had knee replacement. CONCLUSIONS: Opening wedge distal femoral varus osteotomy
      with Puddu plate fixation can be a reliable procedure for the treatment of
      lateral compartment osteoarthritis of the knee associated with valgus deformity.

PMID- 22868702
TI  - Validity and reliability of the Japanese Orthopaedic Association score for
      osteoarthritic knees.
AB  - BACKGROUND: A variety of outcome measures are available to evaluate physical
      impairment and disability in patients with knee osteoarthritis, and most
      physician-rated measures are not validated. The objective of this study was to
      assess the validity and reliability of an observer-based knee scoring system of
      the Japanese Orthopaedic Association (the JOA) commonly used in Japanese clinical
      practice, and to determine demographic variables affecting the score. METHODS: A
      consecutive series of 85 patients with primary knee osteoarthritis completed the
      JOA (four domains pain on walking, pain on ascending or descending stairs, range
      of motion, and joint effusion), two validated patient-rated measures including
      the generic instrument of the Medical Outcomes Study 36-Item Short-Form (the SF
      36) Health Survey, and the disease-specific scale of the Japanese Knee
      Osteoarthritis Measure (the JKOM), and a performance based timed-up-and-go test
      (TUG). Concurrent validity was determined by examining correlations of the JOA
      with the SF-36 and the JKOM. Construct validity was verified by correlating each
      domain of the JOA with objective measurements of TUG using Spearman's rank
      correlation coefficient. Intra- and interobserver reliability and internal
      consistency of the JOA were evaluated with another cohort of 32 patients who had
      a knee disorder at baseline and again at a mean of 18 days later. RESULTS: The
      JOA was significantly correlated with validated patient-rated outcome measures
      (the JKOM, the SF-36), indicating concurrent validity of the JOA. Domains of the
      JOA had significant correlations with the TUG, showing adequate construct
      validity. Intra- and interobserver reliability for the JOA showed a moderate to
      almost perfect agreement, and internal consistency of Cronbach's alpha indicated
      that the JOA score was a highly reliable instrument to assess knee
      osteoarthritis. As a demographic variable, age was highly correlated with the
      JOA. CONCLUSIONS: The JOA, generally used as an observer-derived knee scoring
      system, is a valid and reliable tool for evaluating functional status in patients
      with knee osteoarthritis.

PMID- 22868704
TI  - Glomerular disease: rituximab promising for idiopathic membranous nephropathy.

PMID- 22868703
TI  - Autoimmunity: AAV encompasses two major genetically distinct conditions with
      different autoantibody specificities.

PMID- 22868705
TI  - Fibrosis: a new target for renal fibrosis?

PMID- 22868708
TI  - Paediatrics: Peritoneal dialysis for AKI--time may be of the essence.
AB  - A study by Bojan et al. of neonates and infants who received peritoneal dialysis
      for the treatment of acute kidney injury following cardiac surgery revealed that
      the early initiation of dialysis was associated with a significantly decreased
      mortality rate compared with delayed dialysis.

PMID- 22868709
TI  - Transplantation: is donor T-cell engraftment a biomarker for tolerance?

PMID- 22868711
TI  - Dialysis: first catheter insertion for peritoneal dialysis-surgery versus
      radiology.

PMID- 22868712
TI  - Transplantation: does BMI sufficiently predict renal transplant outcomes?

PMID- 22868714
TI  - Thioflavin-S staining coupled to flow cytometry. A screening tool to detect in
      vivo protein aggregation.
AB  - Amyloid deposits are associated with an increasing number of human disorders,
      including Alzheimer's and Parkinson's diseases. Recent studies provide compelling
      evidence for the existence of amyloid-like conformations in the insoluble
      bacterial inclusion bodies (IBs) produced during the recombinant expression of
      amyloidogenic proteins. This makes prokaryotic cells a physiologically relevant
      system to study the mechanisms of in vivo amyloid deposition. We show here that
      the application of flow cytometry to detect Thioflavin-S (Th-S) fluorescence
      provides a fast, robust, quantitative, non-invasive method to screen for the
      presence of in vivo intracellular amyloid-like aggregates in bacteria, with
      potential application in the analysis of the impact of genetic mutations or
      chemical compounds on the aggregation of disease-associated polypeptides.

PMID- 22868715
TI  - Antioxidant capacities, phenolic compounds and polysaccharide contents of 49
      edible macro-fungi.
AB  - Edible macro-fungi are widely consumed as food sources for their flavors and
      culinary features. In order to explore the potential of macro-fungi as a natural
      resource of bioactive compounds, the antioxidant properties and polysaccharide
      contents of 49 edible macro-fungi from China were evaluated systematically. A
      positive correlation between antioxidant capacity and total phenolic content
      indicated that phenolic compounds could be main contributors of antioxidant
      capacities of these macro-fungi. Furthermore, many bioactive compounds such as
      gallic, homogentisic, protocatechuic, and p-hydroxybenzoic acid were identified
      and quantified. The macro-fungi species Thelephora ganbajun Zang, Boletus edulis
      Bull., Volvariella volvacea Sing, Boletus regius Krombh, and Suillus bovinus
      Kuntze displayed the highest antioxidant capacities and total phenolic contents,
      indicating their potential as important dietary sources of natural antioxidants.

PMID- 22868716
TI  - [Medecine et Sante Tropicales: a new start].

PMID- 22868717
TI  - [Primary health care and the millennium development goals].
AB  - Member countries of the World Health Organization (WHO) met in Alma Ata (8-12
      September 1978) to define and advocate the implementation of primary health care
      (PHC) worldwide, above all, in developing countries, which had a real need to
      review their strategies for meeting the health needs of their populations. They
      did not suspect that 20 years later the vision they displayed would remain
      undeniably relevant. Here we examine the similarities and points of convergence
      of their declaration about PHC with the Millennium Development Goals that seek
      today to reduce poverty across the world. An exhaustive and analytic literature
      review was conducted to collect those similarities. Further analysis of the
      definitions, objectives, principles and recommendations of the Alma Ata
      Declaration and the Millennium Declaration reveals multiple dependencies and
      fundamental points of similarity between these two representations. Almost all
      states have pledged to achieve the eight MDG by 2015: to eradicate extreme
      poverty and hunger, achieve universal primary education, promote gender equality
      and empower women, reduce child mortality, improve maternal health, combat
      HIV/AIDS, malaria and other diseases, ensure environmental sustainability, and
      develop a global partnership for development. The Alma Ata conference defined
      primary health care as essential health care, based on practical methods and
      techniques that are both scientifically sound and socially acceptable,
      universally accessible to all individuals and all families of the community,
      through their full participation and at a cost that the community and countries
      can afford at all stages of their development in the spirit of self-reliance and
      self-determination. It is an integral part of economic and social development.
      The following principles are involved in the achievement of both primary health
      care and the MDG: social equity, community participation, and intersectorality.
      Public health is an essential condition of poverty eradication and MDG
      achievement. Public health issues are central to the problem of sustainable
      development and must therefore remain the focus of attention. It is increasingly
      urgent to break the vicious circle created by the close correlation between
      environmental degradation, poor health, and poverty.

PMID- 22868718
TI  - [The Emerging Voices for Global Health Initiative: an intensive capacity-building
      effort for young researchers from the South].
AB  - Researchers from developing countries, French-speaking nations in particular, are
      underrepresented in the international biomedical and health literature. Various
      initiatives seek to address this problem. This article presents the experience of
      the Emerging Voices for Global Health (EV4GH) program. This initiative provided
      52 young researchers from developing countries with intensive skills and content
      training, with an assortment of complementary components: training in scientific
      writing and presenting skills, immersion in global health and health systems
      research, an innovative presentation of their work at the 52nd colloquium of the
      Institute of Tropical Medicine in Antwerp, and an active role in the first Global
      Symposium on Health Systems Research, supervised by a team of experienced
      researchers/coaches who supported them in the publication of a scientific essay.
      This approach targeting researchers in developing countries and combining the
      development of skills and knowledge through the publication process, merits
      reproduction and encouragement. Young researchers from developing countries
      should not miss out on the second version of this program in October 2012 in
      Beijing, China.

PMID- 22868719
TI  - [Giant anogenital condyloma in an HIV-infected Gabonese woman].

PMID- 22868720
TI  - [The five pillars of family and individual protection against mosquitoes, vectors
      of pathogenic agents].
AB  - Except for yellow fever and encephalitis B, effective vaccines remain unavailable
      against most infectious diseases, and prevention is based mainly upon vector
      control and chemoprophylaxis. The increasing resistance of, respectively,
      mosquitoes and parasites to insecticides and drugs is thus a matter of great
      concern. The best approach is to combine chemoprophylaxis and entomoprophylaxis,
      that is, to use several methods of vector control at different levels to reduce
      the risk of infection and illness from these infectious diseases.

PMID- 22868721
TI  - [Jamot through Bado's eyes].
AB  - The author reviews a biography published in 2011 of Dr. Eugene Jamot (1879-1937),
      a colonial army physician who devoted 25 years of his life to the fight against
      sleeping sickness in Africa. In this book, which includes previously unpublished
      information, the Burkinabe author describes the breakthroughs that tropical
      medicine has made against human African trypanosomiasis, particularly in
      Cameroon. He also highlights the interpersonal conflicts with the colonial
      administration that punctuated Jamot's life in Africa. This article describes the
      circumstances of the discovery of Dr. Jamot's private papers in 1999 and the
      insight that these documents provide into the personality of this illustrious
      army doctor.

PMID- 22868722
TI  - [Feves and left upper-quadrant abdominal pain in a Tunisian child. Amebic abcess
      of the spleen].
AB  - Amebiasis is a rarely localized in the spleen, and its preoperative diagnosis is
      difficult. We report the case of an 11-year-old Tunisian girl who presented with
      fever and left upper-quadrant abdominal pain.

PMID- 22868723
TI  - [Nontuberculous purulent pleural effusion in adults in Yaounde, Cameroon].
AB  - OBJECTIVE: The aim of this study is to analyze current etiologic, bacteriologic
      and prognostic features of nontuberculous purulent pleural effusion in adults in
      Yaounde, Cameroon. METHODS: This study prospectively included 54 adults
      hospitalized for community-acquired nontuberculous purulent pleural effusion in
      the chest-disease clinic of the Jamot Hospital in Yaounde from August 2007 to
      July 2010. RESULTS: The study included 34 men and 20 women with a mean age of
      40.8 +/- 16.4 years. At least one or more predisposing condition or underlying
      disease was found in 59.2%. The most frequent predisposing condition was HIV
      infection, seen in 35.2% of patients. In 92.6% of patients (n=50), purulent
      pleural effusion followed acute bronchopulmonary infection. Positive cultures of
      pleural fluid were found in half the patients. Streptococcus pneumoniae was the
      most common bacteria identified (41.4%) followed by Staphylococcus aureus
      (20.7%). Anaerobic bacteria were isolated in only 13.4% (n=4). Improvement was
      achieved in 79.6% of patients (n=43) and the in-hospital mortality rate was 3.7%.
      The mean duration of hospitalization was 26.8+/-15.6 days. CONCLUSION: This study
      indicates that HIV infection is the most frequent predisposing condition for
      community-acquired nontuberculous purulent pleural effusion in adults in Yaounde.
      The most commonly isolated bacterial pathogen was S. pneumoniae. Although the
      mortality rate of this disease is low, its prevention by proper management of
      acute respiratory tract infection is important.

PMID- 22868724
TI  - [Prevalence of intestinal parasites at Saint-Camille medical center in
      Ouagadougou (Burkina Faso), 1991 to 2010].
AB  - BACKGROUND: Intestinal parasitoses continue to be a major public health problem
      in developing countries. OBJECTIVES: This study sought to evaluate the prevalence
      of intestinal parasites and their coinfection rates in patients attending the
      Saint-Camille medical center in Ouagadougou. Methodology. This retrospective
      study covers the period from 1991 through 2010. RESULTS: In all, 292,148 stool
      samples were analyzed, and 177,672 contained at least one parasite, for a
      prevalence rate of 60.82%. Protozoans accounted for 90.53% of the parasites
      identified (160,838) and helminthes 9.47% (16,834). The most common protozoans
      were Entamoeba histolytica/dispar (39.88%), Trichomonas intestinalis (25.78%) and
      Giardia intestinalis (24.83%). The helminthes encountered most frequently were
      Hymenolepis nana (3.99%) and Ancylostoma spp (3.65%). Globally, the prevalence of
      parasites decreased over the 20-year study period. The prevalence of E.
      histolytica/dispar decreased while that of Giardia intestinalis became more
      frequent. The most common parasitic associations were E. histolytica/dispar-G.
      intestinalis (26.24%) and G. intestinalis-T. intestinalis (20.09%). CONCLUSION:
      Our results indicate that Burkina Faso is a zone at high prevalence of intestinal
      parasitosis, even though this prevalence appears to be decreasing. Appropriate
      strategies should be developed to accelerate the reduction in the incidence of
      these parasites.

PMID- 22868725
TI  - [Imported malaria at Desgenettes Military Hospital in Lyon, France: a
      retrospective study of 115 cases from 2006 to 2008].
AB  - PURPOSE: The purpose of this report is to describe the clinical, epidemiologic,
      and parasitological features and therapeutic modalities associated with cases of
      imported malaria managed at the Desgenettes Military Hospital in Lyon, France.
      MATERIAL AND METHODS: Review of the files of all patients treated for imported
      malaria in the emergency and travel medicine departments of the Desgenettes
      Military Hospital from January 1, 2006, through December 31, 2008. RESULTS: The
      study included 115 patients (13 of them French armed forces personnel). Most
      cases (75.6%) were due to falciparum malaria. Only 28.7% of patients had taken
      proper malaria prophylaxis. Severe symptoms were seen in none of the ambulatory
      care patients versus 22.7% of the hospitalized patients. Quinine treatment was
      used for 67% of ambulatory care patients and 89.4% of those hospitalized.
      CONCLUSIONS: The epidemiologic features observed in the patients described here
      are similar to those reported by the French national reference center for
      imported and autochthonous malaria. The frequent use of quinine for ambulatory
      treatment was not consistent with current guidelines recommending first-line
      treatment with atovaquone-proguanil or artemether-lumefantrine.

PMID- 22868726
TI  - [Syndromic management of sexually transmitted infections in health care
      facilities in Togo: cases reported, 2005-2009].
AB  - OBJECTIVE: The aim of this study was to evaluate trends in sexually transmitted
      infections (STI) in Togo. METHOD: This retrospective descriptive study included
      all STI cases reported from 2005 through 2009. RESULTS: During the study period,
      241,561 STI cases were recorded in the six health regions of Togo, for an annual
      frequency of 48,312 cases. The mean age of patients was 27.4 +/- 12.6 years, and
      those aged from 20 to 30 years accounted for 55.4% of all cases. The sex ratio
      (male/female) was 0.3. The most common STI syndrome was vaginal discharge
      (57.2%), followed by pelvic inflammatory disease (24%), urethral discharge
      (12.1%), and genital ulcer disease (5%). During the study period, the proportion
      of cases involving urethral discharge increased significantly, rising from
      4.20/00 in 2005 to 4.50/00 in 2009 (p = 0.02), while the proportion involving
      genital ulcer disease remained stable (1.60/00 in 2005 and 2009). The proportion
      of cases involving vaginal discharge and pelvic inflammatory disease decreased
      significantly. CONCLUSION: Overall, this study shows that the number of STI cases
      reported by health facilities in Togo was stable from 2005 to 2009. Continued
      epidemiological surveillance is important to document STI trends as part of the
      HIV control program.

PMID- 22868727
TI  - [System of telesonography with synchronous teleconsultations and asynchronous
      telediagnoses (Togo)].
AB  - INTRODUCTION: Ultrasonography is an important nonirradiating diagnostic medical
      imaging procedure, frequently used, especially in urgent circumstances. This
      relatively inexpensive noninvasive examination makes it possible to diagnose
      disorders in various parts of the human body, by examining, for example, the
      abdomen and pelvis, the cardiovascular system, and the muscles and joints.
      Ultrasound is also an operator-dependent examination, in that the quality of the
      result depends on precision in the manipulation of the probe. Unfortunately, many
      small medical centers and isolated sites do not have an appropriate well-trained
      sonographer to perform initial evaluations, and an untrained operator cannot
      capture the appropriate echographic views required for a safe diagnosis of
      current patients, even with realtime vocal guidance (personal data). The lack of
      experienced physicians or qualified technicians means that diagnostic ultrasound
      is not always accessible to patients for rapid examination worldwide, especially
      in Africa, Amazonia or near the North or South Poles. This situation has led to
      the development of a new concept of telemedicine: telesonography, with a remote
      ultrasound diagnosis either in real time (synchronous) or delayed (asynchronous;
      store-and-forward). These systems of real-time telesonography and data
      transmission require expensive and complex technology with sophisticated
      equipment not available in many developing countries. The purpose of this study
      is to design a low-cost real-time system of telesonography for teleconsultations
      with experts and a delayed telediagnostic mode between isolated peripheral
      hospitals and a University Hospital center (UHC). METHODS AND MATERIALS: An IP
      camera and an internet video server were installed in a geographically isolated
      site equipped with an ultrasound machine and an operator with basic training in
      its use. Synchronous teleconsultation (second-opinion diagnosis) is possible via
      internet with a UHC expert. If no ultrasound operator is available at the
      isolated center, volume capture-and-store software is used. Later on, the UHC
      expert uses Echo-Cnes 3D software to reconstruct the organs scanned. The expert
      can then navigate within the reconstructed volume and display any plane. Volume
      capture is performed by tilting (+/- 40 degrees ) to both sides vertically to the
      skin. To locate the probe on the organ acoustic window, the novice operator uses
      acoustic window mapping designed by our laboratory (UMPS-Tours). The system was
      tested between the Tsevie regional hospital in Togo (40 km from Lome, Togo, and
      4500 km from Tours, France) and the UHC at Lome and the Trousseau UHC in Tours.
      RESULTS: With an average internet connection of 2 Mbps, the quality of
      transmission of the background video and ultrasound sequence videos from Tsevie
      towards Lome was satisfactory (16 images/s) with a maximal transmission delay of
      1.5 s (almost in real time). A video conference between the Trousseau UHC in
      Tours, the UHC Campus in Lome and the Tsevie Hospital was possible and the
      bandwidth allowed the Lome experts (radiologists) to perform real-time
      telesonography with very satisfactory results (ultrasound diagnoses obtained) for
      abdominal (n = 5), pelvic (n = 3), obstetric (n = 2), prostate (n = 2) and
      mammary (n = 2) ultrasound, both normal and pathological. Because the doctors at
      Tsevie had minimal experience with ultrasound, complete ultrasound diagnoses were
      obtained by combining remote voice instruction for image capture and full
      diagnosis by Echo-Cnes. Asynchronous telediagnosis was also performed with Tsevie
      operators who lacked ultrasound expertise but could perform the required tilt
      movements (after 3 training sessions). The expert at Trousseau UHC performed real
      time telesonography with the Tsevie Hospital for two cases requiring abdominal
      images and another viewing of the prostate. He also performed asynchronous
      reconstruction of the abdominal organs with Echo-Cnes. A demonstration seminar of
      our platform was organized successfully for 2 days during the 9(th) Congress of
      the French-speaking Black Africa Society of Radiology (SRANF in French) held from
      4 till 6 May 2011 at the hotel EDA OBA. During this seminar, 4 ultrasound
      teleconsultations were performed from the hotel by eminent African radiologists.
      DISCUSSION AND CONCLUSION: This preliminary study, although limited in the number
      of patients, allowed us to assess the technical features of our telesonography
      system. Togo, a developing country with a very modest infrastructure for
      information and communication, was an ideal site for a first test of this
      platform. Our system of remote ultrasound requires the local patient center to be
      equipped simply with a 2D ultrasound machine. The cost is quite low, in
      comparison to the asynchronous techniques requiring 3D devices. The high cost of
      3D or 4D ultrasound machines and their fragility make it difficult to install
      them at the isolated sites and was a serious obstacle in the development of this
      system. If the center already has a 2D device and a computer, the cost to equip
      it with the remaining communications materials is 1,500 ?. The experience in Togo
      clearly highlighted the possibility of teletraining and complete teleradiology
      with our system. The next stage of this work will seek to validate the results of
      this preliminary experience on a larger sample with more precise assessment
      criteria in 2012. The results will allow the widespread dissemination and routine
      use of this system in developing countries.

PMID- 22868728
TI  - [Utility of real-time PCR for the diagnosis of infantile visceral leishmaniasis
      in Algeria].
AB  - Visceral leishmaniasis (VL) is a parasitic disease and serious public health
      problem. The most severe form of all leishmaniases, it is fatal if untreated.
      Currently, it affects close to 540 people per year in Algeria, mainly in Kabylie,
      where it is fatal in 6% of all cases. This disease primarily affects children.
      Its diagnosis is based principally on visualization of parasites in bone marrow
      aspirate. Serologic studies are also used to diagnose VL, as is molecular
      biology, which has been demonstrated to be both faster and more sensitive. The
      aim of our study was to evaluate the utility of real-time polymerase chain
      reaction (RT-PCR) in the diagnosis of VL in endemic areas. Of the 108 samples
      analyzed, 32 were positive according to RT-PCR (29.6%); microscopy yielded
      positive result in 24% and serology in 25.9%. RT-PCR increased the overall number
      of diagnoses detected from 26 to 32, a 20% improvement over microscopic methods.
      In view of the lethal consequences of failure to diagnose this disease, any
      improvement in diagnostic methods provides direct medical benefit.

PMID- 22868729
TI  - [Management of secondary hyperparathyroidism in patients with chronic kidney
      disease undergoing dialysis in Togo].
AB  - PURPOSE: To evaluate the means for diagnosis and treatment of secondary
      hyperparathyroidism in patients with end-stage renal disease undergoing regular
      hemodialysis. METHODS: This prospective investigation studied patients with
      chronic renal kidney disease requiring and receiving hemodialysis at the Tokoin
      University Hospital in Lome, from January 21, 2008, through December 31, 2008.
      RESULTS: The study population comprised 42 patients: 24 men and 18 women ranging
      in age from 20-82 years (mean: 42.62 years). Hyperparathormonemia was found in 20
      of 24 patients for whom parathormonemia was assayed. Two patients with
      hyperthyroidism received a phosphorus chelator, and another went to Egypt for
      renal transplantation. The various other treatments we applied were not
      efficacious. We noted three cases of pathological fractures and one case of
      sudden death. CONCLUSION: The risk of parathyroidism in patients receiving
      hemodialysis is unavoidable. Its course is marked by a risk of sudden death due
      to the cardiovascular damage it causes. Numerous factors impede its effective
      management in Togo.

PMID- 22868730
TI  - [Impact of method of recruitment of blood donors on the prevalence of HIV and HBV
      in Bukavu, DR Congo].
AB  - OBJECTIVES: To determine the impact of the mode of recruitment of blood donors on
      the prevalence of blood-borne infections (HIV and HBV). METHODOLOGY:
      Retrospective cohort study, conducted in Bukavu (eastern DR Congo) 2001-2005.
      HBsAg and HIV tests were analyzed according to age, sex, type, and category of
      donors. Proportions were compared with Pearson Chi2 or Fisher's exact tests and
      Chi2 trend tests, and the strength of associations measured by odds ratios (and
      their 95% CI). RESULTS: Men accounted for 70.2% of the donors, and 88.3% were
      volunteers (n = 3292). Regular donors (n = 7442) provided 75% of the donations .
      The proportion of family donors decreased over time, from 14.3% in 2001 to 5.1%
      in 2005. HIV prevalence was 1% and that of HBsAg 3.7%. Prevalence rates were
      higher among new donors than among regular donors (HIV 1.9% versus 0.2% and HBsAg
      7.3% versus 0.5%), among family donors than among volunteers (4.2% versus 1.6%
      for HIV and 9.9% versus 7% for HBs Ag, and among women than among men (2.8%
      versus 1.6%, OR = 1.79 [1.08-2.96]). Thus new women family donors were 3.75 times
      more likely to be HIV-positive as new volunteers who were women (OR = 3.75 [1.65
      8.55]). The prevalence of HBsAg among new women donors was 5.8%, lower than among
      their male counterparts, 7.9% (OR = 0.71 [0.51-0.98]). CONCLUSION: Risk of
      contamination by seropositive donors was lowest for regular and volunteer blood
      donors.

PMID- 22868731
TI  - [Morbidity and mortality from infectious diseases at the Military Hospital of
      Abidjan, Cote d'Ivoire].
AB  - OBJECTIVES: To determine the proportion of infectious diseases and their
      lethality at the Abidjan Military Hospital. PATIENTS AND METHODS: This cross
      sectional study examined the medical files of patients hospitalized in the
      internal medicine unit of the hospital during 2004. RESULTS: The study included
      668 patients with 855 diseases, 579 of them infectious (67.7%). The prevalence of
      HIV in this population was 41.3%. The main diseases observed were pneumonia (150
      cases; 17.5%), malaria (82 cases; 9.6%), oropharyngeal candidiasis (83 cases;
      9.7%), and tuberculosis (54 cases; 6.3%). The immediate causes of death were
      cerebral toxoplasmosis (27 cases; 39%), pneumopathy (25 cases; 36%), severe
      malaria (7 cases; 10%), tuberculosis (6 cases; 9%), and bacterial meningitis (5
      cases; 7%). The prevalence of HIV infection prevalence among those who died of an
      infectious disease was 74.3%. CONCLUSION: Infectious diseases are the main
      pathologies seen in the internal medicine department of the in Abidjan Military
      Hospital. They were mainly opportunistic infections linked to AIDS. The creation
      of a laboratory of infectious microbiology and of a medical intensive care unit
      appears necessary to optimize management of these infectious diseases.

PMID- 22868732
TI  - [Ulcerative colitis: a case in Togo].
AB  - Ulcerative colitis seems to be rare in sub-Saharan Africa. Because its clinical
      and radiological signs are non-specific, anatomopathologic studies are necessary
      for definitive diagnosis after exclusion of parasitic, bacterial, and viral
      causes. The purpose of this report is to describe a fatal case of ulcerative
      colitis in a 68-year-old woman in Togo.

PMID- 22868733
TI  - [Histoplasmosis: case report from Gabon].
AB  - The purpose of this report is to describe the first case of infection with
      Histoplasma capsulatum variety duboisii in Gabon, in a patient with HIV
      infection.

PMID- 22868734
TI  - [Peganum harmala L. poisoning and pregnancy: two cases in Morocco].
AB  - Peganum harmala L. (wild or Syrian rue) is commonly used as an emmenagogue and
      abortifacient in traditional medicine in the Middle East and North Africa
      including Morocco. The purpose of this report is to describe two cases of Peganum
      harmala L. poisoning in pregnant women. Both cases were treated successfully with
      good maternal-fetal outcome good for mother and child.

PMID- 22868735
TI  - [Severe liver cytolysis could be a marker of the severity of hemorrhagic dengue:
      report of two cases].
AB  - We report two cases of severe dengue fever in persons returned from stays in
      endemic areas during the summer outbreak of 2010. Both presented a hemorrhagic
      syndrome associated with primary hemostasis disorders, neutropenia, and severe
      hepatic cytolysis without any hepatocellular insufficiency. Three days after
      hospitalization, the first patient's AST and ALT levels rose to 80 and 12 times
      the upper reference values respectively, and the second patient's to 12 and 7
      times those values. The second also presented signs of hemodynamic shock. Our
      observations suggest that the combination of severe hepatic cytolysis and
      hemostatic disorders may be a predictive marker of the severity of dengue fever.
      The pathophysiologic mechanisms explaining this severity remain unknown.

PMID- 22868736
TI  - [Thrombosis of the inferior vena cava and right atrium: a rare complication of an
      amebic liver abscess in Dakar, Senegal].
AB  - The liver is the most common site of extra-intestinal amebiasis. Amebic liver
      abscesses can be complicated by rupture, migration to adjacent organs or, more
      rarely, vascular thrombosis. The purpose of this report is to describe the case
      of a 52-year-old Senegalese man hospitalized for painful hepatomegaly associated
      with asymmetric bilateral pulmonary consolidation and fever. Abdominal ultrasound
      revealed a large abscess in the left lobe of the liver with a non-obstructive
      thrombus extending from the inferior vena cava to the right atrium. Doppler
      cardiac ultrasound depicted extensive right atrial thrombus formation. Chest
      radiography showed opacities in both lungs. Sputum smear tests for tuberculosis
      were negative, but amebic serology was positive. Treatment consisted of a
      combination of antibiotics (metronidazole/amoxicillin/clavulanic acid), curative
      heparin therapy, and abscess drainage. Complications during treatment included
      thrombosis of the right chambers of the heart and a suspected pulmonary embolism.
      Outcome was favorable and the thrombi disappeared. The available literature
      confirms the rarity of this complication, which can have severe consequences due
      to embolism.

PMID- 22868737
TI  - [Multifocal pyomyositis after being hit by a truncheon in Gabon].
AB  - Pyomyositis is an acute primary bacterial infection of striated muscle. It
      affects mainly but not only immunocompromised patients, especially in tropical
      areas. The responsible microbe is often found to be Staphylococcus aureus. We
      report here the case of an immunocompetent 17-year-old with multifocal
      pyomyositis from which S. aureus was isolated two weeks after he was hit with a
      truncheon.

PMID- 22868738
TI  - [Seroprevalence of human immunodeficiency virus, hepatitis B virus and hepatitis
      C virus among blood donors in Segou, Mali].
AB  - The purpose of this retrospective study, which examined data collected from
      January 2007 through September 2010, was to evaluate the seroprevalence of human
      immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus
      (HCV) among 2946 new blood donors at the Nianankoro Fomba Hospital (NFH). The
      overall seroprevalence of HIV was 0.88%, of HBV 5.3%, and of HCV 0.55%. Donors
      infected with HIV and HBV were younger than healthy donors, while those infected
      with HCV were older. These findings at the NFH show that HIV, HBV, and HCV remain
      major public health problems in Mali.

PMID- 22868739
TI  - [Impact of severe hypertension in acute heart failure in Brazzaville (Congo)].
AB  - This retrospective study to assess the role of hypertension in acute heart
      failure (HF) reviewed the case records of 86 patients, including 35 men (41%) and
      51 women (59%), mean age 55.6 +/- 18 years, who were hospitalized for an acute
      exacerbation of HF. The cardiovascular risk factors considered were hypertension
      (56%), diabetes (8%), and smoking (13%); 11 patients were alcoholics (13%). HF
      was global in 71 cases (83%). Among the underlying heart diseases, hypertensive
      cardiomyopathy was noted in 22 patients (26%) and valvular disease in 17 patients
      (20%); the precise cause was not elucidated in 40 (47%). A decompensation factor
      was identified in 53 cases (62%). Among the patients admitted on an emergency
      basis for acute HF, the relative risk (RR) of severe hypertension (n = 41, 48%)
      was 3.75 (95% CI: 2.31 to 6.08, p<0.0001), of heart rhythm disorder (n = 25
      cases, 29%) 0.96 (95% CI 0.6 to 1.4, p = 0.5), and of poor adherence to standard
      treatment (n = 16, 18%) 2.2 (95% CI, 1.6 to 2.97, p<0.0001). Other decompensation
      factors were severely impaired renal function in 8 cases (9%) and stroke and
      anemia in 6 cases each (7%).

PMID- 22868740
TI  - [Hemophagocytic syndrome secondary to cavitary pulmonary tuberculosis].
AB  - Hemophagocytic syndrome is due to the activation and nonmalignant proliferation
      of macrophages and T lymphocytes. The purpose of this report is to describe a 25
      year-old man who presented with fever, coughing, and weight loss over the past
      month. Laboratory findings demonstrated pancytopenia, hyperferritinemia, and
      cytolysis. The myelogram showed a hemophagocytic syndrome, and tuberculosis
      bacilli were found in the sputum. Chest radiography and thoracic computed
      tomography depicted a cavitary lesion suggestive of pulmonary tuberculosis.
      Treatment of tuberculosis alone, without an immunosuppressant agent, was
      effective and led to improvement. In a country where tuberculosis is highly
      endemic, hemophagocytic syndrome should be considered in the differential
      diagnosis of patients with active tuberculosis complicated by pancytopenia.

PMID- 22868741
TI  - [Socioeconomic aspects and management of chronic hepatitis B and C in Libreville,
      Gabon].
AB  - INTRODUCTION: Viral hepatitis remains a major public health problem in the sub
      Saharan region. Diagnosis is often made at an advanced stage after a long period
      with few or no symptoms. Late diagnosis impedes optimal management. MATERIALS AND
      METHODS: All patients treated for documented chronic hepatitis B or C from
      January 2001 to December 2009 were identified and the cost of their treatment was
      estimated. Data examined included socioeconomic information, circumstances
      surrounding diagnosis, cost of work-up, cost of curative treatment (pegylated
      interferon + ribavirin for hepatitis C and lamivudine for hepatitis B), and
      overall cost of support. RESULTS: The study included 146 patients (65 women, 81
      men) with a mean age of 34 years. Hepatitis was type B in 89 patients, type C in
      51, and type B/C coinfection in 6 patients. The estimated cost of work-up was 483
      USD for type B and 507 USD for type C. The cost of curative treatment was 1569
      USD for type B and 7842 USD for type C. The estimated cost of support was 407
      USD. The total cost of management was 2459 USD for type B and 8757 USD for type
      C. Only 9 patients received optimal treatment, and it resulted in curing 3 of the
      4 with hepatitis B and 4 of the 5 with hepatitis C. During treatment, progression
      to cirrhosis occurred in two patients, one with hepatitis B and one with
      hepatitis C. CONCLUSION: Financial constraints frequently prevent patients in
      Gabon with hepatitis B and C from receiving optimal care. The creation of a
      national healthcare system in 2008 may lead to cost reductions and improve
      management of this disease in a predominantly young population.

PMID- 22868742
TI  - [Seasonal variations in hematocrit in Kinshasa, Democratic Republic of Congo].
AB  - The aim of the present study was to determine whether the concentration of blood
      cells in plasma varies seasonally in Kinshasa, DR Congo. Changes in hematocrit of
      104 volunteer blood donors in good health were followed during the two seasons of
      the year - rainy and dry. Hematocrit was higher during the rainy season than
      during the dry season.

PMID- 22868743
TI  - [Acute disseminated encephalomyelitis after tetanus vaccination of a pregnant
      woman in Senegal].
AB  - Although neurological complications have been described after tetanus
      vaccinations, they are rare. The authors report a case of acute disseminated
      encephalomyelitis (ADEM) in a 28-year-old pregnant woman at a gestational age of
      10 weeks, admitted 15 days after a tetanus vaccination, with spastic tetraplegia
      and sphincter disturbances. Corticosteroid treatment led to partial recovery of
      the neurological deficit. Differential diagnosis of infectious and demyelinating
      diseases of the central nervous system is difficult in view of clinical and
      laboratory aspects of post-vaccination ADEM. Without any specific diagnostic
      markers, the clinical examination, magnetic resonance imaging and negative
      etiological findings were key to this diagnosis. Medical staff must bear in mind
      the possible complications of this vaccine.

PMID- 22868744
TI  - [Adherence to antiretroviral therapy in HIV-infected patients in Sousse,
      Tunisia].
AB  - Adherence to antiretroviral therapy (ART) is a powerful predictor of survival for
      individuals living with human immunodeficiency virus (HIV). The purpose of this
      cross-sectional study conducted in December 2007 was to assess ART adherence and
      identify its determinants in HIV-infected patients in Sousse, Tunisia. Adherence
      was evaluated in a structured interview, during which questions were asked about
      the number of pills taken, treatment schedule, and any food restrictions within
      the previous 4 days. Determinants of adherence included patient characteristics,
      type of ART, and interpersonal relationships and were assessed from the medical
      records and questionnaire responses. Adherence was assessed in 30 of the 34
      patients receiving ART at the time of the study. Twenty-two patients (73%)
      complied with all daily treatment recommendations and were considered adherent.
      Multivariate analysis showed that the main barriers to adherence were related to
      storage of the medication and doubts about its efficacy. Improvement of
      socioeconomic conditions and better psychosocial support are needed to optimize
      ART adherence by HIV-infected patients in Tunisia.

PMID- 22868745
TI  - [Bacteriological profile of chronic otitis media in the ENT and neck surgery
      department at the Ouagadougou University Hospital Center (Burkina Faso)].
AB  - The specific germs that cause chronic otitis media determine the treatment
      necessary. The purpose of this study was to identify the pathogens involved in
      this disease and to determine the sensitivity of the antibiotics commonly used in
      order to improve treatment. METHODS: This prospective study took place over 12
      months and recorded 53 cases of chronic otorrhea in the ENT department of
      Ouagadougou University Hospital: 41 underwent cytologic and bacteriologic
      analysis. RESULTS: We identified 34 cases of bacterial infection (83%), 2 cases
      of fungal infection (5%) and 5 sterile cultures (12%). The bacteria isolated most
      frequently were Staphylococcus aureus (29%), Pseudomonas aeruginosa (26%) and
      Proteus mirabilis (18%). These organisms were most sensitive to fluoroquinolones
      (84%) and third-generation cephalosporins (77%). However, amoxicillin and
      tetracycline were fairly active against these pathogens, with sensitivity rates
      of respectively 19% and 7%. CONCLUSION: These data could help guide regional
      practitioners in choosing probabilistic antibiotic treatment. Sensitivity testing
      nonetheless remains needed in chronic otorrhea, to verify the efficacy of initial
      treatment and guide adequate care.

PMID- 22868746
TI  - Children with fever and cough at emergency care: diagnostic accuracy of a
      clinical model to identify children at low risk of pneumonia.
AB  - OBJECTIVES: To develop and validate a prediction model for the early
      identification of children with pneumonia in emergency care settings. METHODS:
      This was a diagnostic study with derivation and validation of multivariate
      logistic regression models. This study was carried out on children aged 1 month
      16 years presenting with fever and cough visiting the pediatric emergency
      department of the Erasmus MC-Sophia, Rotterdam, the Netherlands (derivation
      population, n=504); Pediatric Assessment Unit, University Hospitals Coventry and
      Warwickshire NHS Trust, UK (validation population 1, n=420); Accident & Emergency
      Department, Queen's Medical Centre, Nottingham, UK (validation population 2,
      n=366). The outcome pneumonia is defined by the presence of pulmonary
      consolidations on chest radiograph or follow-up. RESULTS: In population 1, 78
      (16%) children were diagnosed with pneumonia; in populations 2 and 3, this number
      was 58 (14%) and 27 (7%), respectively. A simple clinical decision rule on the
      basis of ill appearance, tachypnea, decreased oxygen saturation, and elevated
      serum C-reactive protein categorized children as being at a low (<5%) or a high
      (>16%) risk of pneumonia. The rule yielded a discriminative value of 0.79 (0.69
      0.89) in the Rotterdam population and was validated well in the other two
      populations. CONCLUSION: The risk of pneumonia can be assessed using three key
      clinical characteristics - overall assessment of the severity of illness,
      breathing rate, and oxygen saturation. Serum C-reactive protein contributes to
      the prediction of an intermediate risk of pneumonia in children. Children with a
      low risk of developing pneumonia with vital signs in the normal range can be
      discharged with effective safety netting, requiring neither antibiotics nor
      radiographs.

PMID- 22868747
TI  - Effective strategy for improving instructions for analgesic use in the emergency
      department.
AB  - Pain is a common presenting complaint of emergency department patients. Providing
      instructions that can be easily recalled by patients is an important step in
      enabling patients to manage their pain following discharge. The effect of the
      introduction of written discharge instructions for pain medication on patients'
      recall of instructions was evaluated in this study. A patient-control study
      within a prospective follow-up study was performed. In the first phase, no
      written discharge instructions were available. Patients discharged on analgesics
      filled in a digital questionnaire regarding correct analgesics use. In the second
      phase, patients were discharged with additional written instructions and
      completed the same questionnaire. In the first phase, 40% of patients correctly
      recalled instructions for taking analgesics. In the second phase, significantly
      more patients, 71% (P<0.01), were able to recall the instructions correctly.
      Results of this study support the hypothesis that it makes sense to provide
      patients with written instructions about the appropriate use of analgesics, and
      that emergency departments that are not yet doing this should consider
      introducing this policy. It is a relatively low-cost measure that could lead to a
      significant improvement in quality of care.

PMID- 22868748
TI  - Antibiotic resistance gene abundances associated with antibiotics and heavy
      metals in animal manures and agricultural soils adjacent to feedlots in Shanghai;
      China.
AB  - Eight antibiotic resistance genes (ARGs), 7 heavy metals, and 6 antibiotics were
      quantified in manures and soils collected from multiple feedlots in Shanghai. The
      samples were analyzed to determine if ARG abundances were associated with heavy
      metal concentration and independent of antibiotics. The results revealed the
      presence of chloramphenicol, sulfonamides and tetracyclines at concentration
      ranges of 3.27-17.85, 5.85-33.37 and 4.54-24.66 mg kg(-1), respectively. Typical
      heavy metals, such as Cu, Zn, and As, were detected at concentration ranges of
      32.3-730.1, 75.9-4333.8, and 2.6-617.2 mg kg(-1). All ARGs tested were detected
      in the collected samples except tetB(P), which was absent in animal manures.
      Overall, sulfonamide ARGs were more abundant than tetracycline ARGs. Except for
      sulII, only a weak positive correlation was found between ARGs and their
      corresponding antibiotics. On the contrary, significant positive correlations
      (p<0.05) were found between some ARGs and typical heavy metals. For example, sulA
      and sulIII were strongly correlated with levels of Cu, Zn and Hg. The data
      demonstrated that the presence of ARGs was relatively independent of their
      respective antibiotic inducer. In addition to antibiotics, toxic heavy metals,
      such as Hg, Cu, and Zn, exerted a strong selection pressure and acted as
      complementary factors for ARG abundance.

PMID- 22868749
TI  - Bioremediation of Cd-DDT co-contaminated soil using the Cd-hyperaccumulator Sedum
      alfredii and DDT-degrading microbes.
AB  - The development of an integrated strategy for the remediation of soil co
      contaminated by heavy metals and persistent organic pollutants is a major
      research priority for the decontamination of soil slated for use in agricultural
      production. The objective of this study was to develop a bioremediation strategy
      for fields co-contaminated with cadmium (Cd), dichlorodiphenyltrichloroethane
      (DDT), and its metabolites 1, 1-dichloro-2, 2-bis (4-chlorophenyl) ethylene (DDE)
      and 1, 1-dichloro-2, 2-bis (4-chlorophenyl) ethane (DDD) (DDT, DDE, and DDD are
      collectively called DDs) using an identified Cd-hyperaccumulator plant Sedum
      alfredii (SA) and DDT-degrading microbes (DDT-1). Initially, inoculation with DDT
      1 was shown to increase SA root biomass in a pot experiment. When SA was applied
      together with DDT-1, the levels of Cd and DDs in the co-contaminated soil
      decreased by 32.1-40.3% and 33.9-37.6%, respectively, in a pot experiment over 18
      months compared to 3.25% and 3.76% decreases in soil Cd and DDs, respectively, in
      unplanted, untreated controls. A subsequent field study (18-month duration) in
      which the levels of Cd and DDs decreased by 31.1% and 53.6%, respectively,
      confirmed the beneficial results of this approach. This study demonstrates that
      the integrated bioremediation strategy is effective for the remediation of Cd-DDs
      co-contaminated soils.

PMID- 22868750
TI  - Modeling the dissolution of various types of mixed energetic residues under
      different flow conditions.
AB  - Energetic residues are scattered around active ranges due to the detonation
      events and dissolution is usually the first step for the entry of explosive
      compounds into the environment. The current models for describing the dissolution
      are subject to limitations in either model applicability or generality. This
      study attempted to develop a general model that is applicable to various types of
      energetic residues. Experimental data that were acquired from previous reports
      were used for testing the developed model. The results showed that the model
      captured well the dissolution processes of different types of energetic residues:
      2,4,6-trinitrotoluene (TNT), Tritonal, Composition B, Octol, and Greener
      Insensitive Material (GIM). Moreover, it was observed that the mass transfer
      coefficients of TNT, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and/or
      octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) that were part of the
      energetic residues increased quantitatively with rising flow rates. In addition,
      the values of resistance coefficient, a model parameter, were negligible for the
      drop-impingement experiments, implying that under the conditions of rainfall
      and/or snowmelt flow, the surface attachment effect on the dissolution of
      energetic residues that rest on range soils is trivial. The study herein provides
      a general modeling approach for various types of energetic residues with
      additional insights in regards to their dissolution processes.

PMID- 22868751
TI  - Birth cohort effects on adolescent alcohol use: the influence of social norms
      from 1976 to 2007.
AB  - CONTEXT The substantial changes in adolescent alcohol use prevalence over time
      suggest that population-level environmental factors are important determinants of
      use, yet the potential influence of such environmental factors is inadequately
      understood. OBJECTIVE To investigate whether adolescents in birth cohorts and/or
      time periods characterized by restrictive social norms toward alcohol were at
      decreased risk for alcohol use and binge drinking, controlling for individual
      attitudes (disapproval) toward use. DESIGN, SETTING, AND PARTICIPANTS In 32
      annual national surveys of US high school students, a total of 967 562 students
      contributed outcome data from 1976 through 2007. MAIN OUTCOME MEASURES Frequency
      of past-year alcohol use and any instance of binge drinking (>=5 drinks) in the
      past 2 weeks, analyzed using multilevel models clustering individuals within
      periods and birth cohorts. Period- and cohort-specific social norm scores
      (indicating the proportion disapproving of weekend binge drinking) were modeled
      as predictors, controlling for individual attitudes and demographic
      characteristics. RESULTS Individuals who matured in birth cohorts with more
      restrictive social norms were less likely to use alcohol compared with
      individuals who matured in cohorts with more permissive norms; each 5% increase
      in the cohort-specific disapproval was associated with a 12% decrease in the odds
      of past-year alcohol use (odds ratio = 0.88; 99% CI, 0.87-0.89). The effects of
      cohort-specific disapproval were notably stronger among white adolescents than
      nonwhite adolescents. CONCLUSIONS This study documents the importance of
      considering time-varying population-level risk factors in the study of adolescent
      alcohol use and indicates that, even after an individual's personal attitudes are
      accounted for, risk is shaped by cohort effects whereby the norms within the
      cohort contribute to the risk of adolescent alcohol use.

PMID- 22868752
TI  - Structure of the catalytic core module of the Chaetomium thermophilum family GH6
      cellobiohydrolase Cel6A.
AB  - Cellulases, including cellobiohydrolases and endoglucanases, are important
      enzymes involved in the breakdown of the polysaccharide cellulose. These
      catalysts have found widescale industrial applications, particularly in the paper
      and textile industries, and are now finding use in 'second-generation' conversion
      of biomass to biofuels. Despite this considerable biotechnological application,
      and undoubted future potential, uncertainty remains as to the exact reaction
      mechanism of the inverting cellulases found in the GH6 family of carbohydrate
      active enzymes. In order to gain additional understanding as to how these
      societally beneficial biocatalysts function, the crystal structure of a GH6
      cellobiohydrolase from Chaetomium thermophilum, CtCel6A, has been solved. This
      structure reveals a distorted alpha/beta-barrel fold comprising a buried tunnel
      like active site quite typical of Cel6A enzymes. Analysis of an enzyme-product
      complex (cellobiose in the -3 and -2 subsites and cellotetraose in subsites +1 to
      +4) supports the hypothesis that this group of enzymes act via an atypical single
      displacement mechanism. Of particular note in this analysis is an active-centre
      metal ion, Li(+), the position of which matches the position of the positively
      charged anomeric carbon of the oxocarbenium-ion-like transition state.

PMID- 22868753
TI  - Low-density crystal packing of human protein kinase CK2 catalytic subunit in
      complex with resorufin or other ligands: a tool to study the unique hinge-region
      plasticity of the enzyme without packing bias.
AB  - A low-resolution structure of the catalytic subunit CK2alpha of human protein
      kinase CK2 (formerly known as casein kinase 2) in complex with the ATP
      competitive inhibitor resorufin is presented. The structure supplements previous
      human CK2alpha structures in which the interdomain hinge/helix alphaD region
      adopts a closed conformation correlating to a canonically established catalytic
      spine as is typical for eukaryotic protein kinases. In the corresponding crystal
      packing the hinge/helix alphaD region is nearly unaffected by crystal contacts,
      so that largely unbiased conformational adaptions are possible. This is
      documented by published human CK2alpha structures with the same crystal packing
      but with an open hinge/helix alphaD region, one of which has been redetermined
      here with a higher symmetry. An overview of all published human CK2alpha crystal
      packings serves as the basis for a discussion of the factors that determine
      whether the open or the closed hinge/helix alphaD conformation is adopted.
      Lyotropic salts in crystallization support the closed conformation, in which the
      Phe121 side chain complements the hydrophobic catalytic spine ensemble.
      Consequently, genuine ligand effects on the hinge/helix alphaD conformation can
      be best studied under moderate salt conditions. Ligands that stabilize either the
      open or the closed conformation by hydrogen bonds are known, but a general rule
      is not yet apparent.

PMID- 22868754
TI  - Nanolitre-scale crystallization using acoustic liquid-transfer technology.
AB  - Focused acoustic energy allows accurate and precise liquid transfer on scales
      from picolitre to microlitre volumes. This technology was applied in protein
      crystallization, successfully transferring a diverse set of proteins as well as
      hundreds of precipitant solutions from custom and commercial crystallization
      screens and achieving crystallization in drop volumes as small as 20 nl. Only
      higher concentrations (>50%) of 2-methyl-2,4-pentanediol (MPD) appeared to be
      systematically problematic in delivery. The acoustic technology was implemented
      in a workflow, successfully reproducing active crystallization systems and
      leading to the discovery of crystallization conditions for previously
      uncharacterized proteins. The technology offers compelling advantages in low
      nanolitre crystallization trials by providing significant reagent savings and
      presenting seamless scalability for those crystals that require larger volume
      optimization experiments using the same vapor-diffusion format.

PMID- 22868755
TI  - An engineered PII protein variant that senses a novel ligand: atomic resolution
      structure of the complex with citrate.
AB  - PII proteins are central signal processing units for the regulation of nitrogen
      metabolism in bacteria, archaea and plants. They act in response to cellular
      energy, carbon and nitrogen availability. The central metabolites ATP, ADP and 2
      oxoglutarate, which indicate cellular energy and carbon/nitrogen abundance, bind
      in a highly organized manner to PII and induce effector-molecule-dependent
      conformational states of the T-loop. Depending on these states, PII proteins bind
      and modulate the activity of various regulatory targets. A mutant variant of the
      Synechococcus elongatus PII protein (PII-I86N) has been identified to have
      impaired 2-oxoglutarate binding. Here, the PII-I86N variant was cocrystallized in
      the presence of ATP, magnesium and citrate and its structure was solved at a
      resolution of 1.05 A. The PII-I86N variant bound citrate in place of 2
      oxoglutarate. Citrate binding is mediated primarily by interactions with the ATP
      coordinated magnesium ion and the backbone atoms of the T-loop. Citrate binding
      rearranges the conformation of the T-loop and, consistent with this, citrate
      suppresses the binding of PII-I86N to an NAG kinase variant, which is similar to
      the suppression of PII-NAG kinase complex formation by 2-OG. Based on the
      structures of 2-OG and citrate, homocitrate was suggested as a third ligand and
      an efficient response towards this molecule with different functional properties
      was observed. Together, these data provide a first glimpse of a genetically
      engineered PII variant that senses a new effector molecule.

PMID- 22868756
TI  - The narrow active-site cleft of O-acetylserine sulfhydrylase from Leishmania
      donovani allows complex formation with serine acetyltransferases with a range of
      C-terminal sequences.
AB  - Cysteine is a crucial substrate for the synthesis of glutathione and
      trypanothione, which in turn maintain intracellular redox homeostasis and defend
      against oxidative stress in the pathogen Leishmania donovani. Here, the
      identification, sequencing, characterization and crystal structure at 1.79 A
      resolution of O-acetylserine sulfhydrylase (OASS), a cysteine-biosynthetic
      pathway enzyme from L. donovani (LdOASS), are reported. It shows binding to the
      serine acetyltransferase (SAT) C-terminal peptide, indicating that OASS and SAT
      interact with each other to form a cysteine synthase complex, further confirmed
      by the structure of LdOASS in complex with SAT C-terminal octapeptide at 1.68 A
      resolution. Docking and fluorescence binding studies show that almost all SAT C
      terminus mimicking tetrapeptides can bind to LdOASS. Some peptides had a higher
      binding affinity than the native peptide, indicating that SAT-OASS interactions
      are not sequence-specific. The structure of LdOASS with a designed peptide (DWSI)
      revealed that LdOASS makes more interactions with the designed peptide than with
      the native peptide. In almost all known SAT-OASS interactions the SAT C-terminal
      sequence was shown to contain amino acids with large side chains. Structural
      comparison with other OASSs revealed that LdOASS has a relatively less open
      active-site cleft, which may be responsible for its interaction with the smaller
      amino-acid-containing C-terminal LdSAT peptide. Biochemical studies confirmed
      that LdOASS interacts with SATs from Entamoeba histolytica and Brucella abortus,
      further displaying its sequence-independent and versatile mode of interaction
      with SATs. This implicates a critical role of the size of the active-site cleft
      opening in OASS for SAT-OASS interaction and thus cysteine synthase complex
      formation.

PMID- 22868757
TI  - Structures of the gamma-class carbonic anhydrase homologue YrdA suggest a
      possible allosteric switch.
AB  - The YrdA protein shows high sequence similarity to gamma-class carbonic anhydrase
      (gamma-CA) proteins and is classified as part of the gamma-CA protein family.
      However, its function has not been fully elucidated as it lacks several of the
      conserved residues that are considered to be necessary for gamma-CA catalysis.
      Interestingly, a homologue of gamma-CA from Methanosarcina thermophila and a beta
      carboxysomal gamma-CA from a beta-cyanobacterium have shown that these catalytic
      residues are not always conserved in gamma-CAs. The crystal structure of YrdA
      from Escherichia coli (ecYrdA) is reported here in two crystallographic forms.
      The overall structure of ecYrdA is also similar to those of the gamma-CAs. One
      loop around the putative catalytic site shows a number of alternative
      conformations. A His residue (His70) on this loop coordinates with, or is
      reoriented from, the catalytic Zn(2+) ion; this is similar to the conformations
      mediated by an Asp residue on the catalytic loops of beta-CA proteins. One Trp
      residue (Trp171) also adopts two alternative conformations that may be related to
      the spatial positions of the catalytic loop. Even though significant CA activity
      could not be detected using purified ecYrdA, these structural features have
      potential functional implications for gamma-CA-related proteins.

PMID- 22868758
TI  - Structural plasticity of tubulin assembly probed by vinca-domain ligands.
AB  - Vinca-domain ligands are compounds that bind to tubulin at its inter
      heterodimeric interface and favour heterogeneous protofilament-like assemblies,
      giving rise to helices and rings. This is the basis for their inhibition of
      microtubule assembly, for their antimitotic activities and for their use in
      anticancer chemotherapy. Ustiloxins are vinca-domain ligands with a well
      established total synthesis. A 2.7 A resolution structure of ustiloxin D bound to
      the vinca domain embedded in the complex of two tubulins with the stathmin-like
      domain of RB3 (T(2)R) has been determined. This finding precisely defines the
      interactions of ustiloxins with tubulin and, taken together with structures of
      other vinca-ligand complexes, allows structure-based suggestions to be made for
      improved activity. These comparisons also provide a rationale for the large-scale
      polymorphism of the protofilament-like assemblies mediated by vinca-domain
      ligands based on local differences in their interactions with the two tubulin
      heterodimers constituting their binding site.

PMID- 22868760
TI  - Crystallographic analysis of the conserved C-terminal domain of transcription
      factor Cdc73 from Saccharomyces cerevisiae reveals a GTPase-like fold.
AB  - The yeast Paf1 complex (Paf1C), which is composed of the proteins Paf1, Cdc73,
      Ctr9, Leo1 and Rtf1, accompanies RNA polymerase II from the promoter to the 3'
      end formation site of mRNA- and snoRNA-encoding genes. As one of the first
      identified subunits of Paf1C, yeast Cdc73 (yCdc73) takes part in many
      transcription-related processes, including binding to RNA polymerase II,
      recruitment and activation of histone-modification factors and communication with
      other transcriptional activators. The human homologue of yCdc73, parafibromin,
      has been identified as a tumour suppressor linked to breast, renal and gastric
      cancers. However, the functional mechanism of yCdc73 has until recently been
      unclear. Here, a 2.2 A resolution crystal structure of the highly conserved C
      terminal region of yCdc73 is reported. It revealed that yCdc73 appears to have a
      GTPase-like fold. However, no GTPase activity was observed. The crystal structure
      of yCdc73 will shed new light on the modes of function of Cdc73 and Paf1C.

PMID- 22868761
TI  - The PAD region in the mycobacterial DinB homologue MsPolIV exhibits positional
      heterogeneity.
AB  - Y-family DNA polymerases (dPols) have evolved to carry out translesion bypass to
      rescue stalled replication; prokaryotic members of this family also participate
      in the phenomenon of adaptive mutagenesis to relieve selection pressure imposed
      by a maladapted environment. In this study, the first structure of a member of
      this family from a prokaryote has been determined. The structure of MsPolIV, a Y
      family dPol from Mycobacterium smegmatis, shows the presence of the
      characteristic finger, palm and thumb domains. Surprisingly, the electron-density
      map of the intact protein does not show density for the PAD region that is unique
      to members of this family. Analysis of the packing of the molecules in the
      crystals showed the existence of large solvent-filled voids in which the PAD
      region could be located in multiple conformations. In line with this observation,
      analytical gel-filtration and dynamic light-scattering studies showed that
      MsPolIV undergoes significant compaction upon DNA binding. The PAD region is
      known to insert into the major groove of the substrate DNA and to play a major
      role in shaping the active site. Comparison with structures of other Y-family
      dPols shows that in the absence of tertiary contacts between the PAD domain and
      the other domains this region has the freedom to adopt multiple orientations.
      This structural attribute of the PAD will allow these enzymes to accommodate the
      alterations in the width of the DNA double helix that are necessary to achieve
      translesion bypass and adaptive mutagenesis and will also allow regulation of
      their activity to prevent adventitious error-prone DNA synthesis.

PMID- 22868759
TI  - Significant reduction in errors associated with nonbonded contacts in protein
      crystal structures: automated all-atom refinement with PrimeX.
AB  - All-atom models are essential for many applications in molecular modeling and
      computational chemistry. Nonbonded atomic contacts much closer than the sum of
      the van der Waals radii of the two atoms (clashes) are commonly observed in such
      models derived from protein crystal structures. A set of 94 recently deposited
      protein structures in the resolution range 1.5-2.8 A were analyzed for clashes by
      the addition of all H atoms to the models followed by optimization and energy
      minimization of the positions of just these H atoms. The results were compared
      with the same set of structures after automated all-atom refinement with PrimeX
      and with nonbonded contacts in protein crystal structures at a resolution equal
      to or better than 0.9 A. The additional PrimeX refinement produced structures
      with reasonable summary geometric statistics and similar R(free) values to the
      original structures. The frequency of clashes at less than 0.8 times the sum of
      van der Waals radii was reduced over fourfold compared with that found in the
      original structures, to a level approaching that found in the ultrahigh
      resolution structures. Moreover, severe clashes at less than or equal to 0.7
      times the sum of atomic radii were reduced 15-fold. All-atom refinement with
      PrimeX produced improved crystal structure models with respect to nonbonded
      contacts and yielded changes in structural details that dramatically impacted on
      the interpretation of some protein-ligand interactions.

PMID- 22868762
TI  - X-ray structure of Salmonella typhimurium uridine phosphorylase complexed with 5
      fluorouracil and molecular modelling of the complex of 5-fluorouracil with
      uridine phosphorylase from Vibrio cholerae.
AB  - Uridine phosphorylase (UPh), which is a key enzyme in the reutilization pathway
      of pyrimidine nucleoside metabolism, is a validated target for the treatment of
      infectious diseases and cancer. A detailed analysis of the interactions of UPh
      with the therapeutic ligand 5-fluorouracil (5-FUra) is important for the rational
      design of pharmacological inhibitors of these enzymes in prokaryotes and
      eukaryotes. Expanding on the preliminary analysis of the spatial organization of
      the active centre of UPh from the pathogenic bacterium Salmonella typhimurium
      (StUPh) in complex with 5-FUra [Lashkov et al. (2009), Acta Cryst. F65, 601-603],
      the X-ray structure of the StUPh-5-FUra complex was analysed at atomic resolution
      and an in silico model of the complex formed by the drug with UPh from Vibrio
      cholerae (VchUPh) was generated. These results should be considered in the design
      of selective inhibitors of UPhs from various species.

PMID- 22868763
TI  - The use of workflows in the design and implementation of complex experiments in
      macromolecular crystallography.
AB  - The automation of beam delivery, sample handling and data analysis, together with
      increasing photon flux, diminishing focal spot size and the appearance of fast
      readout detectors on synchrotron beamlines, have changed the way that many
      macromolecular crystallography experiments are planned and executed. Screening
      for the best diffracting crystal, or even the best diffracting part of a selected
      crystal, has been enabled by the development of microfocus beams, precise
      goniometers and fast-readout detectors that all require rapid feedback from the
      initial processing of images in order to be effective. All of these advances
      require the coupling of data feedback to the experimental control system and
      depend on immediate online data-analysis results during the experiment. To
      facilitate this, a Data Analysis WorkBench (DAWB) for the flexible creation of
      complex automated protocols has been developed. Here, example workflows designed
      and implemented using DAWB are presented for enhanced multi-step crystal
      characterizations, experiments involving crystal reorientation with kappa
      goniometers, crystal-burning experiments for empirically determining the
      radiation sensitivity of a crystal system and the application of mesh scans to
      find the best location of a crystal to obtain the highest diffraction quality.
      Beamline users interact with the prepared workflows through a specific brick
      within the beamline-control GUI MXCuBE.

PMID- 22868764
TI  - RCrane: semi-automated RNA model building.
AB  - RNA crystals typically diffract to much lower resolutions than protein crystals.
      This low-resolution diffraction results in unclear density maps, which cause
      considerable difficulties during the model-building process. These difficulties
      are exacerbated by the lack of computational tools for RNA modeling. Here,
      RCrane, a tool for the partially automated building of RNA into electron-density
      maps of low or intermediate resolution, is presented. This tool works within
      Coot, a common program for macromolecular model building. RCrane helps
      crystallographers to place phosphates and bases into electron density and then
      automatically predicts and builds the detailed all-atom structure of the traced
      nucleotides. RCrane then allows the crystallographer to review the newly built
      structure and select alternative backbone conformations where desired. This tool
      can also be used to automatically correct the backbone structure of previously
      built nucleotides. These automated corrections can fix incorrect sugar puckers,
      steric clashes and other structural problems.

PMID- 22868765
TI  - Structure of the branched-chain aminotransferase from Streptococcus mutans.
AB  - The branched-chain amino-acid aminotransferase from Streptococcus mutans (SmIlvE)
      was recombinantly expressed in Escherichia coli with high yield. An effective
      purification protocol was established. A bioactivity assay indicated that SmIlvE
      had aminotransferase activity. The specific activity of SmIlvE towards amino-acid
      substrates was found to be as follows (in descending order): Ile > Leu > Val >
      Trp > Gly. The protein was crystallized using the hanging-drop vapour-diffusion
      method with PEG 3350 as the primary precipitant. The structure of SmIlvE was
      solved at 1.97 A resolution by the molecular-replacement method. Comparison with
      structures of homologous proteins enabled the identification of conserved
      structural elements that might play a role in substrate binding. Further work is
      needed to confirm the interaction between SmIlvE and its substrates by
      determining the structures of their complexes.

PMID- 22868766
TI  - A universal indicator dye pH assay for crystallization solutions and other high
      throughput applications.
AB  - In protein crystallization, as well as in many other fields, it is known that the
      pH at which experiments are performed is often the key factor in the success or
      failure of the trials. With the trend towards plate-based high-throughput
      experimental techniques, measuring the pH values of solutions one by one becomes
      prohibitively time- and reagent-expensive. As part of an HT crystallization
      facility, a colour-based pH assay that is rapid, uses very little reagent and is
      suitable for 96-well or higher density plates has been developed.

PMID- 22868767
TI  - Proline: Mother Nature's cryoprotectant applied to protein crystallography.
AB  - L-Proline is one of Mother Nature's cryoprotectants. Plants and yeast accumulate
      proline under freeze-induced stress and the use of proline in the
      cryopreservation of biological samples is well established. Here, it is shown
      that L-proline is also a useful cryoprotectant for protein crystallography.
      Proline was used to prepare crystals of lysozyme, xylose isomerase, histidine
      acid phosphatase and 1-pyrroline-5-carboxylate dehydrogenase for low-temperature
      data collection. The crystallization solutions in these test cases included the
      commonly used precipitants ammonium sulfate, sodium chloride and polyethylene
      glycol and spanned the pH range 4.6-8.5. Thus, proline is compatible with typical
      protein-crystallization formulations. The proline concentration needed for
      cryoprotection of these crystals is in the range 2.0-3.0 M. Complete data sets
      were collected from the proline-protected crystals. Proline performed as well as
      traditional cryoprotectants based on the diffraction resolution and data-quality
      statistics. The structures were refined to assess the binding of proline to these
      proteins. As observed with traditional cryoprotectants such as glycerol and
      ethylene glycol, the electron-density maps clearly showed the presence of proline
      molecules bound to the protein. In two cases, histidine acid phosphatase and 1
      pyrroline-5-carboxylate dehydrogenase, proline binds in the active site. It is
      concluded that L-proline is an effective cryoprotectant for protein
      crystallography.

PMID- 22868769
TI  - The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein.
AB  - The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc-binding
      phosphoprotein that plays an important role in viral RNA replication and is
      involved in altering signal transduction pathways in the host cell. This protein
      interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The
      1.5 A resolution crystal structure of a complex between the SH3 domain of the Fyn
      tyrosine kinase and the C-terminal proline-rich motif of the NS5A-derived peptide
      APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl(2)
      and belonged to the tetragonal space group P4(1)2(1)2. The asymmetric unit is
      composed of four SH3 domains and two NS5A peptide molecules; only three of the
      domain molecules contain a bound peptide, while the fourth molecule seems to
      correspond to a free form of the domain. Additionally, two of the SH3 domains are
      bound to the same peptide chain and form a ternary complex. The proline-rich
      motif present in the NS5A protein seems to be important for RNA replication and
      virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the
      NS5A C-terminal proline-rich peptide found in this crystallographic structure may
      be important in the virus infection cycle.

PMID- 22868770
TI  - X-ray structure of p38alpha bound to TAK-715: comparison with three classic
      inhibitors.
AB  - The p38alpha mitogen-activated protein kinase regulates the synthesis of pro
      inflammatory cytokines in response to stimulation by a diverse set of stress
      signals. Various different chemotypes and clinical candidates that inhibit
      p38alpha function have been reported over the years. In this publication, the
      novel structure of p38alpha cocrystallized with the clinical candidate TAK-715 is
      reported. Owing to the impact of crystallization conditions on the conformation
      of protein kinases (and in particular p38alpha), the structures of complexes of
      p38alpha with SB-203580, SCIO-469 and VX-745 have also been determined to enable
      in-depth comparison of ligand-induced protein conformations. The impact of
      experimental conditions on p38alpha-inhibitor complex structures, most
      importantly soaking versus cocrystallization, is discussed. Analysis of the
      structures and quantification of the protein-ligand interactions couples ligand
      induced protein conformations to the number of interactions and to inhibitor
      selectivity against the human kinome. This shows that for the design of novel
      kinase inhibitors, selectivity is best obtained through maximization of the
      number of interactions throughout the ATP pocket and the exploitation of specific
      features in the active site.

PMID- 22868768
TI  - Structural and biochemical characterization of a trapped coenzyme A adduct of
      Caenorhabditis elegans glucosamine-6-phosphate N-acetyltransferase 1.
AB  - Glucosamine-6-phosphate N-acetyltransferase 1 (GNA1) produces GlcNAc-6-phosphate
      from GlcN-6-phosphate and acetyl coenzyme A. Early mercury-labelling experiments
      implicated a conserved cysteine in the reaction mechanism, whereas recent
      structural data appear to support a mechanism in which this cysteine plays no
      role. Here, two crystal structures of Caenorhabditis elegans GNA1 are reported,
      revealing an unusual covalent complex between this cysteine and the coenzyme A
      product. Mass-spectrometric and reduction studies showed that this inactive
      covalent complex can be reactivated through reduction, yet mutagenesis of the
      cysteine supports a previously reported bi-bi mechanism. The data unify the
      apparently contradictory earlier reports on the role of a cysteine in the GNA1
      active site.

PMID- 22868771
TI  - High-resolution crystal structure of the isolated ribosomal L1 stalk.
AB  - The crystal structure of the isolated full-length ribosomal L1 stalk, consisting
      of Thermus thermophilus ribosomal protein L1 in complex with a specific 80
      nucleotide fragment of 23S rRNA, has been solved for the first time at high
      resolution. The structure revealed details of protein-RNA interactions in the L1
      stalk. Analysis of the crystal packing enabled the identification of sticky sites
      on the protein and the 23S rRNA which may be important for ribosome assembly and
      function. The structure was used to model different conformational states of the
      ribosome. This approach provides an insight into the roles of domain II of L1 and
      helix 78 of rRNA in ribosome function.

PMID- 22868772
TI  - Dimerization properties of the RpBphP2 chromophore-binding domain crystallized by
      homologue-directed mutagenesis.
AB  - Bacteriophytochromes (BphPs) are biliverdin IXalpha-containing photoreceptors
      that photoconvert between red (Pr) and far-red (Pfr) absorbing states. BphPs are
      one half of a two-component system that transmits a light signal to a histidine
      kinase domain and then to a gene-response regulator. In Rhodopseudomonas
      palustris, synthesis of a light-harvesting complex (LH4) is controlled by two
      BphPs (RpBphP2 and RpBphP3). Despite their high sequence identity (52%), their
      absorption spectra are very different. The spectra of RpBphP2 exhibit classic Pr
      to-Pfr photoconversion, whereas RpBphP3 quenches and a high-energy Pnr state
      emerges [Giraud et al. (2005), J. Biol. Chem. 280, 32389-32397]. Crystallization
      of the chromophore-binding domain (CBD) of RpBphP2 (RpBphP2-CBD) proved to be
      difficult and the structure of RpBphP3-CBD was used to crystallize RpBphP2-CBD*
      using homologue-directed mutagenesis. The structure shows that dimerization is an
      important factor in successful crystallization of RpBphP2-CBD* and arises from an
      N136R mutation. Mutations at this site correlate with an ability to dimerize in
      other truncated BphPs and may also be important for full-length dimer formation.
      Comparison of the RpBphP3-CBD and RpBphP2-CBD* biliverdin IXalpha pockets
      revealed that the former has additional hydrogen bonding around the B and D
      pyrrole rings that may constrain photoconversion to Pfr, resulting in a strained
      photoexcited Pnr state.

PMID- 22868774
TI  - Mental disorders in children and adolescents.

PMID- 22868773
TI  - Continuous beta-turn fold of an alternating alanyl/homoalanyl peptide nucleic
      acid.
AB  - The crystal structure of the PNA (peptide nucleic acid) oligomer H-Lys-HalG-AlaG
      HalC-AlaG-HalC-AlaC-Lys-NH(2) (PNA1, amino acids with D-configuration are
      underlined, Ala = alanyl, Hal = homoalanyl) has been determined by ab initio
      direct methods and refined against 1.0 A data. The asymmetric unit consists of a
      tetrameric cage with almost ideal Watson-Crick C-G base pairing of all the
      guanine and cytosine side-chain substituents. Each PNA strand has a 90 degrees 
      beta-turn every second residue, stabilized by three hydrogen bonds between the
      backbone amides. The first, second, fifth and sixth bases stack on one side of
      the monomer and pair with the corresponding complementary bases of a second
      monomer to form a dimer. The two remaining bases on each side of the resulting
      dimer form Watson-Crick pairs with the complementary bases of a second dimer,
      leading to a unique cage structure. The extra methylene groups in the homoalanyl
      residues enable stacking of the bases with an optimal distance between base
      planes but also with an appreciable lateral displacement (slide).

PMID- 22868776
TI  - Computer-assisted orthopedic surgery.

PMID- 22868777
TI  - Fluoroscopy-based computer-assisted navigation for implant placement and hip
      resurfacing arthroplasty in the proximal femur: the zero-dose C-arm navigation
      approach.
AB  - Abstract In the proximal femur, a high accuracy of implant placement reduces the
      risk of mechanical failure. We have tested a new computer-assisted planning and
      navigation system based on two-dimensional fluoroscopy using the so-called zero
      dose C-arm navigation approach to optimise implant placement in fracture fixation
      and hip resurfacing. The aim of this review is to compare the results of this
      system with the current literature. Use of the novel system enables a minimally
      invasive approach to the hip and results in enhanced accuracy of implant
      placement compared with conventional techniques. Its precision is comparable to
      navigation systems currently in the market. The new system reduces irradiation
      but requires more operation time in comparison with established navigation
      systems. We believe zero-dose C-arm navigation can effectively be used to support
      surgeons in modern orthopaedic and trauma surgery departments, and can
      sufficiently serve the demands of both sections, especially at a time focusing on
      saving costs.

PMID- 22868778
TI  - System architecture for intraoperative ultrasound registration in image-based
      medical navigation.
AB  - Medical navigation systems for orthopedic surgery are becoming more and more
      important with the increasing proportion of older people in the population, and
      hence the increasing incidence of diseases of the musculoskeletal system. The
      central problem for such systems is the exact transformation of the
      preoperatively acquired datasets to the coordinate system of the patient's body,
      which is crucial for the accuracy of navigation. Our approach, based on the use
      of intraoperative ultrasound for image registration, is capable of robustly
      registering bone structures for different applications, e.g., at the spine or the
      knee. Nevertheless, this new procedure demands additional steps of preparation of
      preoperative data. To increase the clinical acceptance of this procedure, it is
      useful to automate most of the data processing steps. In this article, we present
      the architecture of our system with focus on the automation of the data
      processing steps. In terms of accuracy, a mean target registration error of 0.68
      mm was achieved for automatically segmented and registered phantom data where the
      reference transformation was obtained by performing point-based registration
      using artificial structures. As the overall accuracy for subject data cannot be
      determined non-invasively, automatic segmentation and registration were judged by
      visual inspection and precision, which showed a promising result of 1.76 mm
      standard deviation for 100 registration trials based on automatic segmentation of
      magnetic resonance imaging data of the spine.

PMID- 22868779
TI  - Ultrasound-based registration of the pelvic coordinate system in the lateral
      position using symmetry for total hip replacement.
AB  - In total hip replacement, patient placement in the lateral position is preferred
      by many surgeons. However, it complicates registration of the so-called pelvic
      coordinate system that is the standard reference for surgeons to measure cup
      orientation. This coordinate system comprises the anterior pelvic plane and the
      mid-sagittal plane, and it is conventionally registered on the basis of bony
      anatomical landmarks including the left and the right anterior superior iliac
      spine (ASIS). Ultrasound has been suggested for transcutaneous palpation of the
      bone surface. The difficulty in registration of the pelvic coordinate system with
      the patient in the lateral position arises because the contralateral ASIS cannot
      be reached easily by a mechanical pointer and is not accessible by means of an
      ultrasound probe. Up to now, methods to compensate for these missing data have
      not been used in clinical routine. This paper describes a new ultrasound-based
      method that requires neither image segmentation nor statistical shape models and
      uses symmetry to approximate the position of the contralateral ASIS. A detailed
      analysis based on computed tomography data of 60 hips following a cadaver study
      is presented to show the ability of our method to reliably reconstruct the pelvic
      coordinate system. The median angles between ground truth planes and the
      "reconstructed" planes were <2 degrees . By choosing a standard cup orientation
      w.r.t. the "reconstructed" planes, the median abduction and version angle errors
      were <2 degrees , too.

PMID- 22868780
TI  - Component sizing in total knee arthroplasty: patient-specific guides vs. computer
      assisted navigation.
AB  - INTRODUCTION: Patient-specific guides (PSG) and computer-assisted navigation
      (CAN) are technologies that have been developed to improve the accuracy and
      reproducibility of total knee arthroplasty (TKA). The purpose of this study is to
      compare the methodology by which a PSG system and an intraoperative navigation
      system (CAN) perform an anatomical registration and correctly predict femoral
      component size in TKA. METHODS: One hundred and eleven PSG TKA were performed, 30
      of which were concurrently evaluated with CAN. PSG-predicted and CAN-predicted
      femoral component size were compared with the actual component selection. The
      process by which PSG and CAN determines component sizing was evaluated. RESULTS:
      The PSG system was both more accurate and more precise than the CAN navigation
      system in predicting femoral component size in TKA. CONCLUSION: In this study,
      the surgeon's final component selection was more likely to be in accordance with
      the PSG rather than the CAN sizing algorithm. This study suggests that
      intraoperative surface registration may not be as accurate as preoperative three
      dimensional magnetic resonance imaging reconstructions for establishing optimal
      femoral component sizing.

PMID- 22868781
TI  - A new approach to implant alignment and ligament balancing in total knee
      arthroplasty focussing on joint loads.
AB  - Preservation and recovery of the mechanical leg axis as well as good rotational
      alignment of the prosthesis components and well-balanced ligaments are essential
      for the longevity of total knee arthroplasty (TKA). In the framework of the
      OrthoMIT project, the genALIGN system, a new navigated implantation approach
      based on intra-operative force-torque measurements, has been developed. With this
      system, optical or magnetic position tracking as well as any fixation of invasive
      rigid bodies are no longer necessary. For the alignment of the femoral component
      along the mechanical axis, a sensor-integrated instrument measures the torques
      resulting from the deviation between the instrument's axis and the mechanical
      axis under manually applied axial compression load. When both axes are coaxial,
      the resulting torques equal zero, and the tool axis can be fixed with respect to
      the bone. For ligament balancing and rotational alignment of the femoral
      component, the genALIGN system comprises a sensor-integrated tibial trial inlay
      measuring the amplitude and application points of the forces transferred between
      femur and tibia. Hereby, the impact of ligament tensions on knee joint loads can
      be determined over the whole range of motion. First studies with the genALIGN
      system, including a comparison with an imageless navigation system, show the
      feasibility of the concept.

PMID- 22868782
TI  - Precision freehand sculpting for unicondylar knee replacement: design and
      experimental validation.
AB  - Precision freehand sculpting (PFS), is a hand-held semi-active robotic technology
      for bone shaping that works within the surgical navigation framework. PFS can
      alternate between two control modes - one based on control of exposure of the
      cutting bur and another based on the control of the speed of the cutting bur. In
      this study we evaluate the performance of PFS in preparing the femoral bone
      surface for unicondylar knee replacement (UKR). The experiment is designed to
      prepare a synthetic bone for UKR. The implant was a modified commercial design
      that allows accurate measurement of the implant position after it is placed on
      the prepared bone surface. The distal and anterior-distal facets were cut with a
      5 mm cylindrical bur using exposure control. The posterior facet and the post
      holes were cut using a 6-mm spherical bur using speed control. Three users cut
      five specimens each. The performance was evaluated in terms of the implant fit
      and the performance time. The average cut times for the first two cuts combined
      were 4:35 min, and for the posterior cut 3:26 min. The average distance from the
      planned implant position was 0.54 mm (SD 0.23 mm) and the average angular
      difference was 1.08 degrees  (SD 0.53 degrees ).

PMID- 22868784
TI  - Modular structure of HEL protein from Arabidopsis reveals new potential functions
      for PR-4 proteins.
AB  - Plants possess an innate immune system enabling them to defend themselves against
      pathogen attack. The accumulation of newly synthesized pathogenesis-related
      proteins (PRs) is one of the most studied inducible plant defence response. In
      this paper, we report on the characterization of a class I PR4 vacuolar protein
      from Arabidopsis, named AtHEL. The protein has a modular structure consisting of
      an N-terminal hevein-like domain (CB-HEL) and a C-terminal domain (CD-HEL) that
      are posttranslationally processed. Both domains show a strong antifungal
      activity, but they do not have chitinolitic properties. CD-HEL was found to be
      endowed with RNase, but not DNase activity. Molecular modeling carried out on
      both domains revealed that CB-HEL possesses a chitin binding site strictly
      conserved between hevein-type peptides and that the cavity involved in substrate
      interaction of CD-HEL do not show any residue substitution with respect to the
      orthologous wheatwin1 from wheat. Using a fishing for partners approach, CB-HEL
      was found to interact with a fungal fruiting body lectin. According to
      literature, we can hypothesize that CB-HEL could cross the pathogen hyphal
      membrane and that its interaction with a fungal lectin could knock out one of the
      weapons that the fungus uses.

PMID- 22868791
TI  - EDTA-dependent pseudothrombocytopenia: further insights and recommendations for
      prevention of a clinically threatening artifact.
AB  - Ethylenediaminetetra-acetic acid (EDTA) is widely used as anticoagulant in
      laboratory medicine. EDTA-dependent pseudothrombocytopenia is a rare phenomenon
      (i.e., around 0.1% in the general population), which is mostly due to the
      presence of EDTA-dependent antiplatelet antibodies that react optimally between 0
      degrees C and 4 degrees C, recognize the cytoadhesive receptors gpIIb-IIIa,
      stimulate the expression of activation antigens, trigger activation of tyrosine
      kinase, platelet agglutination and clumping in vitro, which finally lead to a
      spuriously decreased platelet count. The reliable and timely identification of
      this artifact is essential, since there a high chance that it may be confused
      with other life-threatening platelet disorders, or otherwise lead to
      inappropriate clinical and therapeutic decision-making. Five basic criteria
      should be fulfilled to raise the clinical suspicion of EDTA-dependent
      pseudothrombocytopenia, i.e., (i) abnormal platelet count, typically
      <100*10(9)/L; (ii) occurrence of thrombocytopenia in EDTA-anticoagulated samples
      at room temperature, but to a much lesser extent in samples collected with other
      anticoagulants and/or kept warmed at ~37 degrees C; (iii) time-dependent fall of
      platelet count in the EDTA specimen; (iv) evidence of platelet aggregates and
      clumps in EDTA-anticoagulated samples with either automated cell counting or
      microscopic analysis; (v) lack of signs or symptoms of platelet disorders.
      Several remedies have been proposed, such as warming the sample to 37 degrees C
      or using additives or specific formulations of anticoagulants including buffered
      sodium citrate, heparin, ammonium oxalate, beta-hydroxyethyltheophylline, sodium
      fluoride, CPT (trisodium citrate, pyridoxal 5'-phosphate and Tris), antiplatelet
      agents, potassium azide, amikacin, kanamycin or other aminoglycosides, and
      calcium replacement with the simultaneous addition of calcium chloride/heparin.
      According to available evidences, the most suitable and practical approach so far
      for most clinical laboratories seems, however, the recollection of blood samples
      using sodium citrate, CPT or calcium chloride/heparin as additives, maintaining
      the specimen at 37 degrees C until the platelet count has been completed.

PMID- 22868792
TI  - Mitochondria as sources and targets of damage in cellular aging.
AB  - Mitochondria are considered as the most important cellular sources and targets of
      free radicals. They are also a source of signalling molecules that regulate cell
      cycle, proliferation, and apoptosis. Denham Harman postulated the free radical
      theory of aging in 1956. Previously Rebecca Gershman showed that radiation
      toxicity could be attributed to free radical damage. Subsequently, Jaime Miquel
      formulated the mitochondrial free radical theory of aging. We have shown that
      mitochondrial size, membrane potential, inner membrane mass and peroxide
      production is altered inside cells in old animals. These result in an increase in
      the oxidative damage to mitochondrial DNA with aging that can be prevented by
      antioxidant supplementation. Aging is also associated with a lower renewal of
      mitochondria. This is mainly due to the lack of reactivity of proliferator
      activated receptor-gamma (PPAR-gamma) coactivator 1alpha (PGC-1alpha) in old
      animals. PGC-1alpha acts as a master regulator of energy metabolism and
      mitochondrial biogenesis and recent evidence shows that it interacts with p53 and
      telomerase. The promotion of mitochondriogenesis is critical to prevent aging. In
      skeletal muscle it has relevance to prevent sarcopenia and frailty.

PMID- 22868793
TI  - Application of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) in Alzheimer's disease.
AB  - Alzheimer's disease is becoming an increasing problem in our aging society.
      According to our knowledge, so far, no effective pharmacotherapy to cure the
      cause of the disease has been developed. Therefore, early diagnosis is needed,
      which will result in implementation of a drug therapy aimed at decreasing and/or
      inhibiting disease development. Mass spectrometry techniques (MS) have a wide
      range of applications in proteomics and the search for biomarkers of
      neurodegenerative disorders, opening new possibilities in diagnostics.
      Identification of proteins in body fluids (like cerebrospinal fluid or blood) is
      possible due to MS spectra analysis. The detected changes in protein
      concentrations are connected with pathological states in an organism and,
      therefore, can be regarded as biomarkers. Developing procedures for proteome
      analysis might result in fast diagnosis, as well as creating better suited
      pharmaceuticals. This paper reviews the search of biomarkers in cerebrospinal
      fluid and blood. Later on, the use of matrix-assisted-laser-desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) in proteomics, focusing on blood
      related biomarkers, is discussed. The aim of the work is also to highlight the
      advantages and disadvantages of MALDI-TOF-based analyses.

PMID- 22868794
TI  - The intellectual contribution of laboratory medicine professionals to research
      papers on laboratory medicine topics published in high-impact general medicine
      journals.
AB  - BACKGROUND: An author is generally regarded as an individual "who has made
      substantial intellectual academic contributions to a published study". However,
      the extent of the contribution that laboratory medicine professionals have made
      as authors of research papers in high-impact medical journals remains unclear.
      METHODS: From 1 January 2004 to 31 March 2009, 4837 original research articles
      appeared in the: New England Journal of Medicine, Lancet, Annals of Internal
      Medicine, JAMA and BMJ. Using authorship as an indicator of intellectual
      contribution, we analyzed articles that included laboratory medicine parameters
      in their titles in an observational cross-sectional study. We also extracted data
      regarding radiological topics that were published during the same time within the
      same journals. RESULTS: Out of 481 articles concerning laboratory medicine
      topics, 380 provided information on the affiliations of the authors. At least one
      author from an institution within the field of laboratory medicine was listed in
      212 articles (55.8%). Out of 3943 co-authors, only 756 (19.2%) were affiliated
      with laboratory medicine institutions. Authors from laboratory medicine
      institutions were listed as the first, last or corresponding authors in 99
      articles (26.1%). The comparative proportions for author affiliation from 55
      radiology articles were significantly higher, as 72.7% (p=0.026) of articles and
      24.8% (p=0.001) of authors indicated an affiliation with a radiology institution.
      Radiology professionals from 72.7% of the articles were listed as either the
      first, last or corresponding authors (p<0.0001). The subgroup analysis revealed
      that laboratory medicine professionals from North America were significantly less
      frequently involved as co-authors than were their colleagues from Europe
      (p=0.04). CONCLUSIONS: Laboratory medicine professionals are underrepresented as
      co-authors in laboratory medicine studies appearing in high-impact general
      medicine journals.

PMID- 22868795
TI  - Laboratory medicine and sports: between Scylla and Charybdis.
AB  - Laboratory medicine is complex and contributes to the diagnosis, therapeutic
      monitoring and follow-up of acquired and inherited human disorders. The regular
      practice of physical exercise provides important benefits in heath and disease
      and sports medicine is thereby receiving growing focus from almost each and every
      clinical discipline, including laboratory medicine. Sport-laboratory medicine is
      a relatively innovative branch of laboratory science, which can provide valuable
      contributions to the diagnosis and follow-up of athletic injuries, and which is
      acquiring a growing clinical significance to support biomechanics and identify
      novel genomics and "exercisenomics" patterns that can help identify specific
      athlete's tendency towards certain types of sport traumas and injuries.
      Laboratory medicine can also provide sport physicians and coaches with valuable
      clues about personal inclination towards a certain sport, health status, fitness
      and nutritional deficiencies of professional, elite and recreational athletes in
      order to enable a better and earlier prediction of sport injuries, overreaching
      and overtraining. Finally, the wide armamentarium of laboratory tests represents
      the milestone for identifying cheating athletes in the strenuous fight against
      doping in sports.

PMID- 22868796
TI  - Assessing the utility of whole genome amplified DNA as a template for DMET Plus
      array.
AB  - BACKGROUND: Large amounts of high quality DNA are typically required for high
      throughput genotyping arrays but sometimes study participant DNA is in limited
      supply. Multiple displacement amplification (MDA)-based whole genome
      amplification is an in vitro technique that permits the genetic analysis of
      limited amounts of high molecular weight genomic DNA (gDNA). METHODS: The
      performance of MDA-whole genome amplified DNA (wgaDNA) as a template for DMET
      Plus (Affymetrix) was assessed. wgaDNA was generated from gDNA from three HapMap
      CEU cell lines and 11 breast cancer patients. One HapMap sample and three patient
      samples were randomly selected for replication to assess reproducibility.
      Accuracy was assessed by comparing the wgaDNA genotypes with gDNA genotypes. The
      kappa (kappa) statistic was used to measure genotype concordance between paired
      gDNA-wgaDNA and wgaDNA-wgaDNA samples. Copy number variants (CNV) were not
      included in concordance analysis in this study. RESULTS: A good genotype call
      rate of 98.8%+/-1.06% (mean+/-standard deviation, 1931 markers) was observed for
      all 18 wgaDNA samples with three samples having call rates lower than 98%. High
      genotype concordance rates were observed between four HapMap wgaDNA-gDNA pairs
      (98.5%, kappa=0.9817, p<0.0001, 1931 markers) and 14 patient wgaDNA-gDNA pairs
      (100%, kappa=1.00, p<0.0001, 19 markers among CYP2D6 and CYP2C19). Excellent
      genotype concordance was also observed between four independently amplified
      duplicate samples (98.0%, kappa=0.9745; p<0.0001, 1931 markers). CONCLUSIONS: MDA
      produced wgaDNA provides accurate and reproducible genotypes with the DMET Plus
      array and is therefore a suitable template for this targeted pharmacogenetic
      genotyping array.

PMID- 22868797
TI  - Effect of acceleration forces during transport through a pneumatic tube system on
      ROTEM(r) analysis.
AB  - BACKGROUND: ROTEM(r) is considered a helpful point-of-care device to monitor
      blood coagulation in emergency situations. Centrally performed analysis is
      desirable but rapid transport of blood samples is an important prerequisite. The
      effect of acceleration forces on sample transport through a pneumatic tube system
      on ROTEM(r) should be tested at each institution to exclude a pre-analytical
      influence. The aims of the present work were: (i) to investigate the effect of
      pneumatic tube transport on ROTEM(r) parameters; (ii) to compare blood sample
      transport via pneumatic tube vs. manual transportation; and (iii) to determine
      the effect of acceleration forces on ROTEM(r) parameters. METHODS: This is a
      single centre study with 20 healthy volunteers. Five whole blood samples were
      transferred to the central haematology laboratory by either normal transport or
      pneumatic delivery with different speed and acceleration forces. EXTEM, INTEM,
      FIBTEM and APTEM were analysed in parallel with two ROTEM(r) devices and
      compared. Acceleration forces were measured during transport with two different
      instruments. RESULTS: Increment of transport time, speed and distance resulted in
      an augmentation of acceleration forces and peaks. All results of the ROTEM(r)
      analysis after manual transport or pneumatic delivery were within normal range.
      However, increase in acceleration forces resulted in minimally but statistically
      significant changes in multiple ROTEM(r) parameters. The higher the acceleration
      forces, the more ROTEM(r) parameters are influenced. CONCLUSIONS: Acceleration
      forces during transport through a pneumatic tube system have an influence on
      ROTEM(r) parameters. Prior to transfer blood samples via pneumatic tube system
      these influences should be tested to exclude clinically relevant blood
      coagulation activation in vitro.

PMID- 22868798
TI  - The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron
      deficiency anemia.
AB  - BACKGROUND: Serum ferritin is the best single laboratory test to diagnose iron
      deficiency anemia (IDA). Ferritin levels <20 MUg/L are highly specific for IDA,
      and ferritin levels >100 MUg/L usually exclude IDA. However, ferritin
      concentrations between 20 and 100 MUg/L are often inconclusive. The objective of
      this study was to improve the diagnosis of IDA when ferritin levels are
      inconclusive. METHODS: We evaluated the predictive performance of classic
      (ferritin, mean corpuscular volume, transferrin and serum iron) and modern
      [reticulocyte hemoglobin content, serum transferrin receptor and soluble
      transferrin receptor (sTfR)/log(ferr)] iron status parameters to diagnose IDA in
      2084 anemic, non-hospitalized patients. The results were validated in an
      independent cohort of 274 anemic patients. RESULTS: In our study population, 29%
      (595 patients) of the patients had a ferritin level between 20 and 100 MUg/L,
      hampering diagnosis of IDA. None of the classic or modern parameters was capable
      of completely separating the IDA population from the non-IDA population. However,
      using a new parameter, the transferrin/log(ferritin) ratio, the IDA and non-IDA
      populations can be completely separated. At a cut-off value of 1.70, the
      transferrin/log(ferritin) ratio indicates IDA in 29% of the patients with
      inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is
      a practical new tool that improves diagnosis of iron deficiency when ferritin
      levels are inconclusive.

PMID- 22868799
TI  - Instructions on laboratory monitoring in 200 drug labels.
AB  - BACKGROUND: Monitoring drug treatment is important to assess the therapeutic
      effects and to prevent adverse drug reactions. Unfortunately, the clinical
      evidence for monitoring is often missing. To attain evidence-based laboratory
      monitoring and to improve patient safety it is mandatory for the clinical chemist
      to develop effective and rational methods for monitoring. The legal source for
      this evidence-based information is the drug label. We analysed frequency, nature,
      and applicability of instructions on laboratory monitoring described in 200 drug
      labels. METHODS: The applicability of instructions was assessed with an adapted
      Systematic Information for Monitoring score. Seven items of information were
      evaluated: why to monitor, what to monitor (essential), when to start or stop
      monitoring, how frequently to monitor, critical value (essential) and how to
      respond (essential). Each item scored one point when information was described
      specifically, otherwise the score was zero. Instructions were applicable if all
      three essential items scored. RESULTS: In 131 drug labels, 566 instructions on
      laboratory monitoring were identified, an average of 2.8 per drug label. Kidney,
      liver, electrolyte, and drug monitoring were important biomarker categories
      (71%). The median applicability score was 2.1 (0-6) and 95 (17%) instructions
      were applicable. Six determinants were associated with applicable instructions:
      kidney (OR 7.0; 95% CI 4.4-11.3), creatine phosphokinase (4.5; 1.5-13.6), drug
      selection (6.8; 4.0-11.7), dose adjustments (2.4; 1.5-3.7), year on the market
      2000-2007 (2.6; 1.1-6.1) and statins (4.8; 2.5-9.0). CONCLUSIONS: Drug labels
      frequently describe instructions on laboratory monitoring, but these are
      ambiguous and incomplete and clinical applicability for the professional is
      limited.

PMID- 22868800
TI  - Lipid peroxidation markers in Crohn's disease: the associations and diagnostic
      value.
AB  - BACKGROUND: Crohn's disease (CD) is an incurable and difficult to diagnose
      condition. While high sensitive C-reactive protein (CRP) remains the best
      biochemical marker, we evaluated the diagnostic usefulness of lipid peroxidation
      indices. METHODS: Malondialdehyde/thiobarbituric acid-reactive substances
      (MDA/TBARS), peroxidation potential (PP), lipid hydroperoxides (ROOH), oxidized
      low density lipoprotein (oxLDL), and oxLDL antibodies (OLAB) were assessed in 52
      CD patients and 99 volunteers and referred to clinical activity, inflammation,
      nutritional and antioxidant status. RESULTS: MDA/TBARS were higher in CD while
      oxLDL and PP decreased in active disease and ROOH and OLAB did not differ. oxLDL
      and PP negatively and OLAB positively correlated with CD activity. MDA/TBARS
      positively correlated with IL-6 and SOD-1 and negatively with catalase. IL-6 and
      SOD-1 explained 24% in MDA/TBARS variability. PP negatively correlated with CRP,
      platelets, and IL-6 and positively with glutathione peroxidase-1, paraoxonase-1,
      cholesterol, triglycerides, and albumins. Cholesterol and CRP explained 57% in PP
      variability. oxLDL negatively correlated with IL-1 and IL-6 and positively with
      glutathione peroxidase-1, paraoxonase-1, cholesterol, and albumins. Paraoxonase-1
      explained 17% of oxLDL variability. OLAB positively correlated with IL-1
      explaining 10% in its variability and negatively with cholesterol. MDA/TBARS were
      the best predictor of CD, comparable to CRP, with high specificity (MDA/TBARS
      sensitivity and specificity: 75% and 90%; CRP: 76% and 93%). Combined assessment
      of MDA/TBARS and CRP improved sensitivity (94%) corresponding with acceptable
      specificity (81%). CONCLUSIONS: MDA/TBARS are elevated in CD and may help to rule
      the disease out, while the combined evaluation with CRP may serve for CD
      confirmation. oxLDL and PP depended on substrate availability, decreased in CD.

PMID- 22868801
TI  - Elevated levels of Nepsilon-homocysteinyl-lysine isopeptide in patients on long
      term hemodialysis.
AB  - BACKGROUND: Nepsilon-homocysteinyl-lysine (Nepsilon-Hcy-Lys), a product of
      proteolysis of Nepsilon-homocysteinylated proteins, has been discovered recently.
      We sought to investigate the presence of Nepsilon-Hcy-Lys in patients on long
      term hemodialysis (HD) and its association with markers involved in
      atherosclerotic vascular disease. METHODS: We studied 86 patients on long-term
      (median, 45 months) HD and 95 apparently healthy controls. Nepsilon-Hcy-Lys and
      total homocysteine (tHcy) were assayed using high-performance liquid
      chromatography. Paraoxonase 1 (PON1), asymmetric dimethylarginine (ADMA), folate,
      8-isoprostaglandin F2alpha(8-iso-PGF2alpha), plasminogen activator inhibitor-1
      (PAI-1), C-reactive protein (CRP), together with antibodies against Nepsilon
      homocysteinylated albumin and hemoglobin, were also measured. RESULTS: Nepsilon
      Hcy-Lys was detected in 15 HD patients (17.4%). Those patients had 3.1-times
      lower PON1 (p<0.0001), 20% higher ADMA (p<0.0001), 30% higher PAI-1 (p<0.0001),
      10% lower total cholesterol (p=0.001) and LDL-cholesterol (p<0.0001), together
      with 20% lower triglycerides (p<0.0001) compared with subjects without measurable
      Nepsilon-Hcy-Lys. Nepsilon-Hcy-Lys levels correlated with PON1 (r=-0.62,
      p<0.0001), ADMA (r=0.58, p<0.0001) and PAI-1 (r=0.59, p<0.0001). Folic acid
      supplementation, tHcy, folate, autoimmune response to Nepsilon-Hcy-proteins, and
      oxidative stress were not associated with the presence of Nepsilon-Hcy-Lys. PON1
      is the only independent predictor of the presence of Nepsilon-Hcy-Lys in HD
      patients. None of controls had measurable Nepsilon-Hcy-Lys in serum. CONCLUSION:
      The presence of Nepsilon-Hcy-Lys in HD patients is relatively infrequent and
      associated with lipid profile, endothelial dysfunction and impaired fibrinolysis,
      regardless of tHcy and folate levels.

PMID- 22868802
TI  - Interleukin-1alpha gene variants influence bone mineral density and the risk of
      osteoporotic hip fractures in elderly Slovenian people.
AB  - BACKGROUND: Osteoporosis is a skeletal disorder, characterized by low bone mass
      and microarchitectural deterioration of bone tissue, leading to increased risk of
      fracture. Recently, the role of age-related pro-inflammatory cytokines, such as
      interleukin (IL)-1alpha, in stimulating bone resorption has been suggested. As
      osteoporosis has a strong genetic background, the aim of our study was to
      evaluate the association of two IL-1alpha gene single nucleotide polymorphisms
      (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic phenotypes
      as well as to find the association with IL-1alpha gene expression in human bone
      tissue. METHODS: Genotyping was performed in 671 Slovenian participants, 125
      elderly men, 490 post- and 56 premenopausal women. Bone mineral density (BMD) at
      the lumbar spine, femoral neck and total hip were measured. Biochemical markers
      of bone turnover were measured in women. RESULTS: Significant association of
      GG/TA haplotype with higher femoral neck and total hip BMD in elderly men and
      women was shown (p=0.009 and 0.030, respectively). In men, the association of the
      GG/GG haplotype with higher femoral neck BMD was of limited statistical
      significance (p=0.050). In women, significant association of studied genetic
      variants with serum C-terminal crosslinking telopeptides of type I collagen and
      bone alkaline phosphatase were found (p=0.033 and 0.029, respectively). No
      influence on IL-1alpha expression was found. Finally, significantly lower odds
      ratio for hip fracture associated with the presence of TA haplotype was found
      (p=0.026). CONCLUSIONS: Our results of the association of IL-1alpha gene single
      nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with
      osteoporotic features indicate its role in pathogenesis of osteoporosis. However,
      these findings need further functional and clinical confirmation.

PMID- 22868803
TI  - Novel method to dissociate platelet clumps in EDTA-dependent
      pseudothrombocytopenia based on the pathophysiological mechanism.
AB  - BACKGROUND: EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro
      phenomenon of platelet clumping that leads to spuriously low platelet counts by
      automatic hematology analyzers. The mechanism is not clearly defined, but is
      known as an immunologically mediated phenomenon due to the presence of EDTA
      dependent antiplatelet auto-antibodies that induce platelet clumping. The purpose
      of this study was to identify antiplatelet antibodies in EDTA-PTCP samples and to
      design a method to dissociate platelet clumps based on the pathophysiological
      mechanism. METHODS: The antiplatelet antibody was investigated using direct and
      indirect immunofluorescent flow cytometric methods in 23 EDTA-anticoagulated
      whole blood (WB) samples and 12 serum samples of EDTA-PTCP patients,
      respectively. A novel mixture containing 9 mmol/L CaCl(2) and 0.1 unit/L sodium
      heparin, that provides calcium replacement while curbing coagulation, was
      designed to dissociate platelet clumps. The effect on dissociation was
      demonstrated in 26 samples of EDTA-PTCP and compared with the established method
      of kanamycin supplementation. RESULTS: The direct test was positive for IgM and
      IgG antiplatelet antibody in 60.9% and 4.4% of patients, respectively [mean
      median fluorescence intensity (MFI) of 223.9 and 128.4, respectively]. The
      indirect test was positive for IgM antiplatelet antibody in 58.3% of patients
      (mean MFI of 123.4). The novel method dissociated the platelet clumps with a mean
      increased platelet count of 242.3% and was equivalent in efficiency to kanamycin
      supplementation. CONCLUSIONS: The novel method is an easily applicable and
      efficient measure that allows dissociation of platelet clumps, based on the
      pathophysiological mechanism of EDTA-PTCP.

PMID- 22868804
TI  - Proficiency testing/external quality assurance for the PFA-100((r)).
AB  - BACKGROUND: Platelet function testing is integral to haemostasis investigations
      and the Platelet Function Analyser-100 (PFA-100((r))) is globally the most
      utilised primary haemostasis-screening instrument. External Quality Assurance
      (EQA) (or proficiency testing) is critical to ensuring quality of test practice,
      but EQA for platelet function is logistically challenging and actual test
      challenges generally not possible. METHODS: A novel approach was therefore
      developed whereby a range of formulated test tubes are distributed to EQA
      participants to which citrated normal whole blood collected on site is added,
      thereby creating test material that can be locally evaluated. Several exercises
      have been conducted over the past four years (total of 18 challenges, most
      designed to mimic an aspirin effect or a mild or severe primary haemostasis
      defect, tested in 26-47 laboratories). RESULTS: Numerical results for PFA
      100((r)) closure times (CTs) and interpretive comments provided by participants
      were analysed. Reported CTs for each challenge were within limits of expectation
      and good reproducibility was evidenced by repeated challenges. Coefficients of
      variation (CVs) generated for two PFA-100((r)) cartridge types (C/ADP and C/Epi)
      for challenges [median (range): 14.8 (3.9-29.5) and 13.9 (0.6-29.5)] was similar
      to those obtained using native whole blood [15.6 (14.2-18.9) and 17.3 (13.5
      20.5)]. Interpretations were in general also consistent with expectations and
      test data provided by laboratories. CONCLUSIONS: In conclusion, an EQA process
      for the PFA-100((r)) has been developed that includes a highly reproducible test
      challenge process, not only proving the concept is possible for platelet function
      testing, but also providing a valuable mechanism for monitoring and improving
      laboratory performance.

PMID- 22868805
TI  - Interference of selected flavonoid aglycons in platelet aggregation assays.
AB  - BACKGROUND: Flavonoids are widely distributed across the plant kingdom and are
      therefore common ingredients in an everyday diet. Some flavonoids have a
      potential to affect platelet aggregation; most often antiaggregatory effects of
      flavonoids are observed. The objective of this research was to evaluate the in
      vitro effect of a selected set of flavonoids on platelet aggregation in whole
      blood. METHODS: The effect of five selected flavonoids (pinocembrin-7
      methylether, epicatechin, hesperetin, 6-hydroxyflavone and 3,6-dihydroxyflavone)
      on platelet aggregation was studied in the citrated whole blood samples collected
      from 75 healthy volunteers. A Multiplate((r)) impedance analyzer and five
      different aggregation inducers (ADP, arachidonic acid, collagen, ristocetin and
      TRAP-6) were utilized for the analysis of samples. RESULTS: Minimal
      antiaggregatory concentrations (MINaAC) of flavonoids in individual tests were
      reported in the following ranges: 0.12-1.91 MUM; 15.26-244.14 MUM; 15.26-122.07
      MUM; and 0.06-15.26 MUM for ADP, collagen, TRAP-6 and ristocetin aggregation
      inducers, respectively. When arachidonic acid was used for induction of platelet
      aggregation, a proaggregatory effect was observed for pinocembrin-7-methylether,
      epicatechin, hesperetin and 3,6-dihydroxyflavone, while the expected
      antiaggregatory effect was observed only for 6-hydroxyflavone (MINaAC=7.63 MUM).
      CONCLUSIONS: Flavonoids interfere with in vitro platelet aggregation assays
      exhibiting either anti- or proaggregatory effects in concentration ranges that
      can be achieved in circulation by dietary intake. Thus, dietary intake of
      flavonoids should be taken into account when interpreting the results of whole
      blood platelet aggregation.

PMID- 22868806
TI  - Monocyte chemoattractant protein-1 and paraoxonase-1 and 3 levels in patients
      with sepsis treated in an intensive care unit: a preliminary report.
AB  - BACKGROUND: There is considerable interest in the research of molecules
      modulating the acute inflammatory response in patients with sepsis. Paraoxonases
      (PON) are antioxidant and anti-inflammatory enzymes that inhibit the production
      of the monocyte chemoattractant protein-1 (MCP-1). This preliminary study
      investigated changes in PON status and MCP-1 concentrations in critically ill
      patients with severe sepsis treated in an ICU and their relationship with the
      evolution of disease. METHODS: This was a longitudinal, prospective and
      observational study on 15 patients with sepsis, studied at baseline and on days
      1, 2, 5, 7 and 10 of their stay in the ICU. In all the patients we measured serum
      PON1 and PON3 concentrations, PON1 paraoxonase and lactonase activities, serum
      MCP-1 concentrations, and several standard biochemical and haematological
      parameters. RESULTS: MCP-1 concentration significantly decreased with the
      resolution of sepsis, and this decrease was especially important during the first
      5 days of hospitalisation. PON1 and PON3 tended to decrease during the first 5
      days in ICU and significantly increased in days 7 and 10. Linear regression
      analysis showed significant and direct correlations among serum MCP-1
      concentration and lactate levels at baseline. At the end of stay, PON1
      paraoxonase and lactonase activities were significantly correlated with organ
      system function measurements. CONCLUSIONS: We observed an inverse pattern between
      changes in MCP-1, and PON1 and PON3 levels in patients with sepsis, this was
      related to the resolution of their infection after receiving treatment in an ICU.

PMID- 22868807
TI  - Association between ischemia-modified albumin, homocysteine, vitamin B(12) and
      folic acid in patients with severe sepsis.
AB  - BACKGROUND: The aim of the present study was to investigate serum ischemia
      modified albumin (IMA), homocysteine, malondialdehyde (MDA), vitamin B(12) and
      folic acid levels in patients with severe sepsis, compared to healthy control
      subjects. Also, we examined associations of these parameters with high
      sensitivity C-reactive protein (hsCRP) in patients with severe sepsis and healthy
      control subjects. METHODS: This study was performed on 71 (40 male, 31 female)
      patients with severe sepsis aged 18-65 years and 70 (34 male, 36 female) healthy
      control subjects aged 18-65 years. Samples of patients were obtained at study
      entry within 24 h of onset of severe sepsis. RESULTS: Serum IMA, homocysteine and
      MDA levels of the patients with severe sepsis were significantly higher than
      those of the healthy control subjects (p<0.01 for IMA and homocysteine, and
      p<0.001 for MDA). There was no significant difference between serum vitamin B(12)
      and folic acid levels of the groups. Serum hsCRP levels were positively
      correlated with IMA (p<0.01) and MDA (p<0.01) in the patients with severe sepsis.
      CONCLUSIONS: Our findings show that IMA may be useful as a prognostic biomarker
      because it can indicate the severity of illness in patients with sepsis.

PMID- 22868808
TI  - Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish
      sepsis from systemic inflammatory response syndrome in human subjects.
AB  - BACKGROUND: Serum microRNAs may be useful biomarkers for diagnosing human
      diseases. We investigated serum levels of miR-15a and miR-16 in patients with
      sepsis and systemic inflammatory response syndrome (SIRS) without infection.
      METHODS: We enrolled 166 sepsis patients, 32 SIRS patients, and 24 normal
      controls. Serum miR-15a and miR-16 expression levels were determined by
      quantitative reverse transcriptase polymerase chain reaction assays (qRT-PCR).
      RESULTS: Serum miR-15a (p<0.001) and miR-16 (p<0.05) were both significantly
      higher in sepsis patients compared with normal controls, and miR-15a (p<0.001)
      and miR-16 (p<0.01) levels in SIRS patients were also significantly higher than
      those in normal controls. Serum miR-15a and miR-16 levels were not correlated
      with white blood cell counts. Receiver operating characteristic curves showed
      that miR-15a had the highest area under the curve of 0.858 [95% confidence
      interval (CI) 0.800-0.916] for the diagnosis of sepsis compared with C reactive
      protein and procalcitonin with areas under the curve of 0.572 (95% CI 0.479
      0.665; p=0.198) and 0.605 (95% CI 0.443-0.767; p=0.168), respectively. When its
      cut-off point was set at 0.21, serum miR-15a had a sensitivity of 68.3% and a
      specificity of 94.4%. CONCLUSIONS: Serum miR-15a and miR-16 can both distinguish
      sepsis/SIRS from normal controls. miR-15a may be a biomarker that distinguishes
      between sepsis and SIRS.

PMID- 22868809
TI  - The predictive value of immature granulocyte count and immature myeloid
      information in the diagnosis of neonatal sepsis.
AB  - BACKGROUND: To determine the predictive value of the immature granulocyte count
      and the immature myeloid information in neonatal early onset sepsis we examined
      133 blood samples of patients admitted to our neonatal intensive care unit.
      METHODS: Measurements were performed using the Sysmex XE-2100, an automated
      hematological analyzer. Patients were divided into two groups: 1) symptomatic
      neonates with diagnosis of early onset sepsis; and 2) controls including
      asymptomatic neonates who were admitted because of prematurity, low birth weight,
      or delayed postnatal transition. RESULTS: The number of immature granulocytes and
      the immature myeloid information were significantly elevated in neonates with
      early onset sepsis compared to controls (median 280/MUL vs. 50/MUL, p=0.049 and
      639/MUL vs. 89/MUL, p<0.0001, respectively). CONCLUSIONS: Automated
      determinations of immature granulocytes and immature myeloid information seem to
      be useful adjunctive methods in the diagnosis of neonatal early onset sepsis.

PMID- 22868810
TI  - Hypophosphatemia, fever and prolonged length of hospital stay in seronegative PCR
      positive patients as compared to seropositive patients with early acute Q fever
      pneumonia.
AB  - BACKGROUND: Query fever (Q fever) is a zoonotic infection, caused by the
      intracellular Gram-negative coccobacillus Coxiella burnetii. From 2007 until
      2010, a large Q fever outbreak has occurred in the Netherlands. We studied
      traditional and less common inflammation markers in seronegative and seropositive
      patients with acute Q fever pneumonia to identify markers that distinguish
      different disease stages and predict disease severity. METHODS: A total of 443
      adult patients presenting at the Emergency Department with community-acquired
      pneumonia were included in a prospective etiologic study. Patients with acute Q
      fever pneumonia were identified by PCR and/or serology. Patient characteristics,
      clinical symptoms, pneumonia severity and inflammation markers were assessed upon
      presentation. Duration of symptoms, prior therapy and length of hospital stay
      were retrieved from the hospital information system. RESULTS: In all, 40 patients
      with acute Q fever pneumonia were identified. Of these, 29 were seronegative and
      11 seropositive at presentation. C-reactive protein (CRP) was the only
      inflammation marker increased in all seronegative and seropositive patients but
      no significant difference was observed between groups. In seronegative patients,
      hypophosphatemia was more common (p=0.01), and length of hospital stay was longer
      (p=0.02). However, there was no significant difference in pneumonia severity
      index. Furthermore, phosphate levels were inversely correlated with body
      temperature (p=0.003). CONCLUSIONS: In acute Q fever pneumonia, CRP is the only
      traditional inflammation marker adequately reflecting disease activity. Patients
      with seronegative acute Q fever pneumonia present with hypophosphatemia and have
      prolonged length of hospital stay when compared to seropositive patients,
      suggesting an increased disease severity.

PMID- 22868811
TI  - Diagnostic value of HE4 for ovarian cancer: a meta-analysis.
AB  - BACKGROUND: Ovarian cancer (OC) is the second most common gynecological cancer
      and the first cause of death from gynecological malignancy in Western Europe and
      the USA. While human epididymis-specific protein 4 (HE4) has been reported as a
      predictive diagnostic index, it has not been widely accepted because of
      inconsistent conclusions. The aim of this study was to evaluate the diagnostic
      value of HE4 systematically for ovarian cancer. METHODS: All relevant original
      studies about HE4 in the diagnosis of ovarian cancer published from January 1974
      to May 2011 were retrieved. By measuring methodological qualities, 12 papers were
      selected for this study, while 531 articles were searched. The overall diagnostic
      sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood
      ratio (LR-), and area under the receiver operating characteristic curve (AUC-ROC)
      were used to evaluate the diagnostic value of HE4 for ovarian cancer using the
      Meta-DiSc statistical software. RESULTS: There were 2607 subjects included in
      this meta-analysis. The sensitivity, specificity, LR+ and LR- (95% confidence
      interval) of HE4 was 0.800 (0.770-0.827), 0.916 (0.902-0.929), 10.271 (6.982
      15.109) and 0.228 (0.181-0.287), respectively. The area under the summary
      receiver operating characteristic (sROC) curve of HE4 was 0.946. The index of Q*
      was 0.885. CONCLUSIONS: HE4 was found to be better than CA125 as an auxiliary
      indicator for the diagnosis of ovarian cancer in terms of better sensitivity,
      specificity, LR+ and LR-.

PMID- 22868812
TI  - Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in
      chronic hemodialysis patients.
AB  - BACKGROUND: The aim of our study was to measure reactive oxygen metabolites
      (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible
      association with cardiovascular disease (CVD) and mortality. METHODS: We measured
      ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the
      follow-up and all-cause and CVD-related mortality. RESULTS: The levels of ROMs
      presented a median value of 270 (238.2-303.2) CARR U (interquartile range). We
      created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of
      273 CARR U. Patients with ROMs levels >=273 CARR U were significantly older, had
      higher C-reactive protein levels and lower creatinine concentrations. The
      prevalence of CVD was higher in patients with ROMs levels >=273 (87.1%) than in
      those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were
      significantly higher in patients with CVD (317+/-63.8) than in those without
      (242.7+/-49.1; p<0.0001). At multiple regression analysis, age, creatinine and C
      reactive protein were independent factors associated with ROMs. At multiple
      logistic regression analysis the association between ROMs and CVD was independent
      (OR: 1.02, 95% CI: 1.00-1.05; p=0.03). Twenty six patients developed
      cardiovascular (CV) events during the follow-up. Of these, seven were in the
      group with ROMs levels <273 CARR U and 19 in the group with ROMs levels >=273
      CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI:
      1.01-1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00-1.02; p=0.045) were
      independently associated with CV events in the follow-up. CONCLUSIONS: ROMs are
      independently associated with CVD and predict CV events in chronic HD patients.

PMID- 22868813
TI  - Methylenetetrahydrofolate reductase C677T and reduced folate carrier 80 G>A
      polymorphisms are associated with an increased risk of conotruncal heart defects.
AB  - BACKGROUND: Folic acid has an important role during embryologic development,
      particularly the development of the cardiovascular system. METHODS: We analyzed
      the involvement of eight polymorphisms in genes related to folic-acid metabolism,
      5,10-methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate
      dehydrogenase (MTHFD1), transcobalamin (TCN2), reduced folate carrier (RFC),
      nicotinamide-N-methyltransferase (NNMT) and natriuretic peptide precursor A
      (NPPA) as risk factors of conotruncal heart defects. RESULTS: In single-locus
      analyses, the genotype frequencies of MTHFR rs1801133 C>T were 18.4% (CC), 50.4%
      (CT), and 31.1% (TT) in the subjects with conotruncal heart defects and 31.6%
      (CC), 52.9% (CT), and 15.4% (TT) in control subjects, and the difference was
      significant (p=0.001). Logistic regression analyses revealed that, if the MTHFR
      rs1801133 CC homozygote genotype was used as the reference group, subjects
      carrying the TT variant homozygote had a significant 3.46-fold [odds ratio (OR)
      3.46; 95% confidence interval (CI) 1.83-6.55] increased risk of conotruncal heart
      defects. If the RFC rs1051266 GG homozygote genotype was used as the reference
      group, subjects carrying the GA variant heterozygote had a significant 1.68-fold
      (OR 1.68; 95% CI 1.02-2.78) increased risk of conotruncal heart defects. In
      stratification analyses, the MTHFR rs1801133 C>T genotype was associated with an
      increased risk for tetralogy of Fallot (TOF) and transposition of great artery
      (TGA) in homozygote comparisons, the dominant genetic model, and the recessive
      genetic model. The RFC rs1051266 GA genotype was associated with an increased
      risk for TGA compared with wild-type homozygotes and, in the dominant genetic
      model, the RFC rs1051266 GA/AA genotype was also associated with a significantly
      increased risk of TGA compared with RFC rs1051266 GG genotypes. CONCLUSIONS:
      These data suggest that genotypes for the MTHFR C677T and RFC rs1051266
      polymorphism might be associated with the risk of conotruncal heart defects.

PMID- 22868814
TI  - Oxidative stress as a predictor of cardiovascular events in coronary artery
      disease patients.
AB  - BACKGROUND: Enhanced oxidative stress has been associated with atherosclerosis
      and coronary artery disease (CAD). However, the predictive value of circulating
      oxidative stress biomarkers for cardiovascular events (CE) in patients with CAD
      has remained poorly understood. AIM: To assess the prognostic significance of
      reactive oxygen metabolites, estimated as index of oxidative stress in serum
      samples by means of a commercial kit (ROMs, Diacron, Italy) on the rate of
      mortality and major adverse CE (MACE) in CAD. METHODS: A study of 93 consecutive
      patients with angiographically documented CAD (75 males, age: 68+/-10 years,
      mean+/-SD) was made during a mean follow-up of 66 months until the occurrence of
      one of the following CE: cardiac and all cause death, non-fatal myocardial
      infarction and coronary revascularization [percutaneous transluminal coronary
      angioplasty (PTCA) and coronary artery bypass grafting (CABG)]. Patient data were
      retrospectively collected from the Institute's electronic databank that saves
      demographic, clinical, instrumental and follow-up data of all patients admitted
      to our department. RESULTS: The Kaplan-Meier survival estimates showed a
      significantly worst outcome in patients presenting elevated ROM level (>75th
      percentile, corresponding to 481 AU) (log rank=11, 7.5, 5.1; p<0.001, p<0.01,
      p<0.05 for cardiac and all cause death and MACEs, respectively). In a
      multivariate Cox regression model, elevated oxidative stress remained a
      significant predictor of cardiac and all cause death [hazard ratio (HR) 3.9, 95%
      confidence interval, 95% (CI) 1.4-11.1, p=0.01; HR=2.6, 95% CI 1.1-6.2, p=0.02)
      and MACE (HR=1.8, 95% CI 1.1-3.1, p=0.03)]. CONCLUSIONS: The estimation of ROMs
      may represent an additional prognostic tool in the assessment of CE in CAD
      patients.

PMID- 22868815
TI  - Behavioral and clinical correlates of high-sensitivity C-reactive protein in
      Japanese men and women.
AB  - BACKGROUND: Inflammation has been implicated in the pathogenesis of
      cardiovascular disease, type 2 diabetes mellitus and cancer. Serum concentration
      of high-sensitivity C-reactive protein is a good biomarker of chronic low-grade
      inflammation. Few studies have evaluated relative importance of behavioral and
      clinical covariates of high-sensitivity C-reactive protein in Japanese
      population. METHODS: The study subjects were men and women aged 49-76 years from
      the cohort study of lifestyle-related diseases between February 2004 and July
      2006. Analysis of covariance and multiple linear regression analysis were used to
      estimate geometric means of high-sensitivity C-reactive protein and trends of
      association. RESULTS: Smoking, body mass index, hypertension, type 2 diabetes
      mellitus, elevated non-high density lipoprotein cholesterol, prudent dietary
      pattern were independently associated with serum high-sensitivity C-reactive
      protein in both men and women. High-sensitivity C-reactive protein concentrations
      were lowest in men with a moderate intake of alcohol (<30 mL/day). In men,
      smoking and body mass index accounted for 28% and 26% of the variation in high
      sensitivity C-reactive protein, respectively, while body mass index accounted for
      60% of the variation of high-sensitivity C-reactive protein in women.
      CONCLUSIONS: Smoking and body mass index in men, and body mass index in women,
      were major correlates of serum high-sensitivity C-reactive protein in Japanese
      people.

PMID- 22868816
TI  - Hemoglobin Rambam has a constant retention time on the Tosoh G8 and interferes
      with the measurement of HbA(1c).

PMID- 22868817
TI  - Measurement of glycated hemoglobin in a patient with homozygous hemoglobin E.

PMID- 22868818
TI  - BSN graduates' perceptions of liberal education.
AB  - An integrative, professional nursing curriculum grounded in liberal education has
      the capacity to prepare empowered, competent, and humanistic nurses as well as
      informed, democratic citizens. The purpose of this qualitative research study was
      to explore the meaning of the lived- experience of recent Bachelor of Science in
      Nursing (BSN) graduates from a small private college in a curriculum grounded in
      a liberal education. The phenomenological psychological philosophy of Paul
      Colaizzi (1978) provided the theoretical foundation for this study. Twelve recent
      BSN graduates were interviewed. The three major themes that emerged were
      "confusion of the meaning of liberal education", "the value of liberal
      education", and "descriptions of the learning experiences."In conclusion, most
      recent graduate nurses were able to articulate the values of liberal education to
      professional nursing education after they understood the meaning of the term. The
      study suggests recommendations for strengthening curricular connections between
      liberal and professional learning .

PMID- 22868819
TI  - Intensive and Standard Blood Pressure Targets in Patients With Type 2 Diabetes
      Mellitus: Systematic Review and Meta-analysis.
AB  - BACKGROUND Treatment of hypertension in patients with diabetes mellitus (DM) has
      been shown to improve cardiovascular outcomes; however, the value of intensive
      blood pressure (BP) targets remains uncertain. We sought to determine the
      effectiveness and safety of treating BP to intensive targets (upper limit of 130
      mm Hg systolic and 80 mm Hg diastolic) compared with standard targets (upper
      limit of 140-160 mm Hg systolic and 85-100 mm Hg diastolic) in patients with type
      2 DM. METHODS Using electronic databases, bibliographies, and clinical trial
      registries, we conducted a systematic review and meta-analysis to identify
      randomized trials enrolling adults diagnosed as having type 2 DM and comparing
      prespecified BP targets. Data on study characteristics, risk for bias, and
      outcomes were collected. Random-effects models were used to pool relative risks
      and risk differences for mortality, myocardial infarction, and stroke. RESULTS
      The use of intensive BP targets was not associated with a significant decrease in
      the risk for mortality (relative risk difference, 0.76; 95% CI, 0.55-1.05) or
      myocardial infarction (relative risk difference, 0.93; 95% CI, 0.80-1.08) but was
      associated with a decrease in the risk for stroke (relative risk, 0.65; 95% CI,
      0.48-0.86). The pooled analysis of risk differences associated with the use of
      intensive BP targets demonstrated a small absolute decrease in the risk for
      stroke (absolute risk difference, -0.01; 95% CI, -0.02 to -0.00) but no
      statistically significant difference in the risk for mortality or myocardial
      infarction. CONCLUSION Although the use of intensive compared with standard BP
      targets in patients with type 2 DM is associated with a small reduction in the
      risk for stroke, evidence does not show that intensive targets reduce the risk
      for mortality or myocardial infarction.

PMID- 22868820
TI  - Resection of anterior cranial base meningiomas with intra- and extracranial
      involvement via a purely endoscopic endonasal approach.
AB  - OBJECTIVE: The complete resection of anterior cranial base meningiomas with intra
      and extracranial involvement is always challenging. We describe our experience
      of treating such meningiomas via a purely endoscopic endonasal approach (EEA).
      METHODS: Eight patients with intra- and extradural meningiomas were operated via
      EEA. In this study, we describe the operative technique, and analyze the degree
      of resection, complications and the clinical outcomes. RESULTS: The complete
      resection of meningiomas with intra- and extracranial involvement was achieved in
      all patients using EEA. Preoperative visual symptoms were improved or resolved in
      all cases. One patient experienced a postoperative cerebrospinal fluid leak and
      delayed meningitis. No patient in our series experienced a new neurological
      deficit after surgery or recurrence in the follow-up period (18-60 months).
      CONCLUSION: Our limited experience indicates that EEA is feasible and safe for
      the complete resection of anterior cranial base meningiomas with intra- and
      extracranial involvement in one stage in selected cases.

PMID- 22868821
TI  - The preventative effects of sunitinib malate observed in the course from non
      castration to castration LNCaP xenograft prostate tumors.
AB  - PURPOSE: The aim of the study was to evaluate the effect of the agent SU-11248
      (sunitinib malate) in the course from non-castration to castration LNCaP
      xenograft prostate tumors. METHODS: BALB/c nude mice were injected with human
      androgen-dependent prostate cancer cell line (LNCaP) and divided into two groups:
      castration and non-castration. Then the LNCaP-bearing mice were treated with
      sunitinib (40 mg/kg daily, 0.2 ml p.o. for 3 weeks). Both groups were paired with
      control groups in which the mice were given water by gavaging daily. The kidneys,
      livers, hearts, lungs, spleens, stomachs, intestines, skins, and other parts of
      all the mice were observed carefully during the study. RESULTS: At the end of the
      3-week dosing schedule, the tumors of the sunitinib-treated mice grew
      significantly slower than those of control group. Adverse reactions were not
      significantly found in the mice. We examined the impact of sunitinib on tumor
      growth and tumor angiogenesis through molecular factors representative of
      vascular endothelial growth factor receptors (VEGFR-2) and platelet-derived
      growth factor receptors (PDGFR-beta) families, and of apoptosis (Bcl-2), and of
      proliferation (Ki67). The Ki67 and Von Willebrand factor expression of the
      control group was higher than that of the treated group. However, there was no
      significant difference observed between treated and control groups for apoptosis
      induction (Bcl-2). Immunohistochemistry, Western blot, and quantitative
      polymerase chain reaction results showed both VEGFR-2 and PDGFR-beta expression
      in the control group was higher than that of the sunitinib-treated group.
      CONCLUSION: Sunitinib is safe and effective for treating tumors in the course
      form non-castration to castration groups in LNCaP xenograft prostate tumors. It
      is potentially beneficial as a prevention and treatment measure for clinical
      patients with prostate cancer, especially in the course from androgen-dependent
      prostate cancer to castration-resistant prostate cancer.

PMID- 22868823
TI  - The cycling physiology of Miguel Indurain 14 years after retirement.
AB  - Age-related fitness declines in athletes can be due to both aging and detraining.
      Very little is known about the physiological and performance decline of
      professional cyclists after retirement from competition. To gain some insight
      into the aging and detraining process of elite cyclists, 5-time Tour de France
      winner and Olympic Champion Miguel Indurain performed a progressive cycle
      ergometer test to exhaustion 14 y after retirement from professional cycling (age
      46 y, body mass 92.2 kg). His maximal values were oxygen uptake 5.29 L/min (57.4
      mL . kg-1 . min-1), aerobic power output 450 W (4.88 W/kg), heart rate 191
      beats/min, blood lactate 11.2 mM. Values at the individual lactate threshold
      (ILT): 4.28 L/min (46.4 mL . kg-1 . min-1), 329 W (3.57 W/kg), 159 beats/min, 2.4
      mM. Values at the 4-mM onset of blood lactate accumulation (OBLA): 4.68 L/min
      (50.8 mL . kg-1 . min-1), 369 W (4.00 W/kg), 170 beats/min. Average cycling gross
      efficiency between 100 and 350 W was 20.1%, with a peak value of 22.3% at 350 W.
      Delta efficiency was 27.04%. Absolute maximal oxygen uptake and aerobic power
      output declined by 12.4% and 15.2% per decade, whereas power output at ILT and
      OBLA declined by 19.8% and 19.2%. Larger declines in maximal and submaximal
      values relative to body mass (19.4-26.1%) indicate that body composition changed
      more than aerobic characteristics. Nevertheless, Indurain's absolute maximal and
      submaximal oxygen uptake and power output still compare favorably with those
      exhibited by active professional cyclists.

PMID- 22868822
TI  - Increased physical activity combined with more eating occasions is beneficial
      against dyslipidemias in children. The Healthy Growth Study.
AB  - PURPOSE: To identify lifestyle patterns associated with blood lipid levels in
      children. METHODS: A representative sample of 2,043 schoolchildren (9-13 years)
      participated in a cross-sectional epidemiologic study conducted in 77 primary
      schools in four large regions in Greece. Dietary intakes, breakfast patterns and
      eating frequency, physical activity levels, sleep duration, anthropometric and
      physical examination data, biochemical indices and socioeconomic information
      (collected from parents) were assessed in all children. Principal component
      analysis was used to identify the lifestyle patterns. RESULTS: A lifestyle
      pattern of more screen time, shorter sleep duration and higher sugar-sweetened
      beverage consumption was inversely associated with HDL cholesterol (beta = 
      0.077; P < 0.001) and positively associated with total/HDL cholesterol ratio
      (beta = 0.049; P = 0.025). Furthermore, a lifestyle pattern of more eating
      occasions and higher moderate-to-vigorous physical activity (MVPA) levels was
      inversely associated with total cholesterol (beta = -0.064; P = 0.006), LDL (low
      density lipoprotein) cholesterol (beta = -0.065; P = 0.004) and total/HDL (high
      density lipoprotein) cholesterol ratio (beta = -0.043; P = 0.049) in multivariate
      models. Finally, children with MVPA levels and eating frequency higher than that
      corresponding to the second quartile of this lifestyle pattern (i.e., > 44.8 min
      of MVPA per day and > 4.7 meals per day) were 29.7, 32.6 and 43.1 % less likely
      of having abnormal levels of total cholesterol, LDL and total/HDL cholesterol
      ratio, respectively, according to the National Cholesterol Education Program
      (NCEP) cutoff points. CONCLUSIONS: A lifestyle pattern of more than approximately
      45 min of MVPA and 5 eating occasions per day was significantly associated with
      reduced likelihood of dyslipidemias in schoolchildren (9-13 years).

PMID- 22868824
TI  - Disk and joint morphology variations on coronal and sagittal MRI in
      temporomandibular joint disorders.
AB  - OBJECTIVES: This study aims to assess the disk morphology and the condyle
      position in subjects with temporomandibular (TMJ) disk displacements on sagittal
      and coronal magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-four
      TMJs (from 37 patients) with positive clinical TMD symptoms according to the
      RDC/TMD axis I protocol were evaluated by 1.5 T MRI. Disk position, disk
      morphology, sagittal and coronal condyle position, joint effusion, joint space,
      and coronal condyle angulation were evaluated. Multivariate logistic regression
      was used to explore the relationship between disk displacement and MRI variables.
      RESULTS: Disk displacement with reduction (DDR) was found in 36.48 % and without
      reduction (DDwR), in 21.62 % of the joints. Disk displacement was anterior in
      35.1 %, anterior-medial in 13.5 %, and anterior-lateral in 9.45 % of cases. The
      thickened posterior band (94.48 OR, p = 0.001) and the posterior condyle position
      (4.57 OR, p = 0.03) were more likely found on sagittal MRI in disk displacements.
      On coronal slices, the disk displacement was significantly associated with the
      distance from the most medial condyle point to the midplane (p < 0.05).
      CONCLUSIONS: Disk displacement is associated with changes of disk shape, disk
      dimension, and condyle position on sagittal MRI. A significant variation of the
      distance from the most medial condyle point to the midplane in disk displacement
      was found on coronal MRI. CLINICAL RELEVANCE: Our study highlights the existence
      of changes on coronal MRI in TMD patients which should be assessed for better
      understanding of the clinical evolution of temporomandibular disorders.

PMID- 22868825
TI  - Computer-aided evaluation of preparations for CAD/CAM-fabricated all-ceramic
      crowns.
AB  - OBJECTIVE: The aim of this study was the evaluation of preparations from general
      dental practitioners for zirconia crowns and their correlation with clinical
      recommendations using a digital approach. MATERIAL AND METHOD: Seventy-five
      datasets of left first upper molars (FDI 16) prepared for single zirconia crowns
      by general dental practitioners were analyzed using a computer-aided design
      software (LAVA(TM) Design; 3M ESPE, Seefeld, Germany) and a 3D-inspection
      software (COMETinspect(r)plus version 4.5; Steinbichler Optotechnik, Neubeuern,
      Germany). Evaluated parameters were convergence angle, undercuts, interocclusal
      reduction, abutment height, and design of preparation margin. RESULTS: The mean
      convergence angle was determined to be 26.7 degrees . The convergence angle in
      the mesiobuccal to distopalatal dimension was significantly the highest (31.7
      degrees ), and the abutment height showed a mean value of 4.1 mm. Convergence
      angle and abutment height showed a negative correlation. Seventy-three percent of
      the evaluated locations revealed a margin design conforming to ceramic
      restorations. In over 30 % of the cases, the interocclusal reduction was
      insufficient. Generally, no preparation fulfilled all recommendations. Five (6.66
      %) of the preparations fulfilled four criteria, 16 (21.33 %) preparations
      fulfilled three criteria, 31 (41.33 %) fulfilled two criteria, 17 (22.66 %)
      preparations fulfilled one criterion, and 6 (8 %) fulfilled no criterion.
      CONCLUSIONS: Within the limitations of this study, most general dental
      practitioners seem to have difficulties fulfilling all clinical recommendations
      given for the preparation of zirconia crowns. The presented digital approach
      seems to be a useful method to evaluate the preparation geometry. CLINICAL
      RELEVANCE: The correct preparation geometry represents an important prerequisite
      for the success of all-ceramic full crowns. As preparations clearly need to be
      improved, the approach presented could be the basis of a future tool to increase
      preparation quality in practice and education by direct objective feedback.

PMID- 22868826
TI  - Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug
      6MePdR and their combination therapy in murine melanoma model.
AB  - The PNP/6-methylpurine 2'-deoxyriboside (6MePdR) system is an efficient gene
      directed enzyme prodrug therapy system with significant antitumor activities. In
      this system, Escherichia coli purine nucleoside phosphorylase (ePNP) activates
      nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP). The Salmonella
      typhimurium PNP (sPNP) gene has a 96-% sequence homology in comparison with ePNP
      and also has the ability to convert 6MePdR to 6MeP. In this study, we used tumor
      targeting S. typhimurium VNP20009 expressing endogenous PNP gene constitutively
      to activate 6MePdR and a combination treatment of bacteria and prodrug in B16F10
      melanoma model. The conversion of 6MePdR to 6MeP by S. typhimurium was analyzed
      by HPLC and the enzyme activity of sPNP was confirmed by in vitro (tetrazolium
      based colorimetric assay) MTT cytotoxicity assay. After systemic administration
      of VNP20009 to mice, the bacteria largely accumulated and specifically delivered
      endogenous sPNP in the tumor. In comparison with VNP20009 or 6MePdR treatment
      alone, combined administration of VNP20009 followed by 6MePdR treatment
      significantly delayed the growth of B16F10 tumor and increased the CD8(+) T-cell
      infiltration. In summary, our results demonstrated that the combination therapy
      of S. typhimurium and prodrug 6MePdR is a promising strategy for cancer therapy.

PMID- 22868827
TI  - Highly sensitive detection and quantification of the pathogen Yersinia ruckeri in
      fish tissues by using real-time PCR.
AB  - Yersinia ruckeri is the causative agent of enteric redmouth diseases (ERM) and
      one of the major bacterial pathogens causing losses in salmonid aquaculture.
      Since recent ERM vaccine breakdowns have been described mostly attributed to
      emergence of Y. ruckeri biotype 2 strains, rapid, reproducible, and sensitive
      methods for detection are needed. In this study, a real-time polymerase chain
      reaction (PCR) primer/probe set based on recombination protein A (recA) gene was
      designed and optimized to improve the detection of Y. ruckeri. The primer/probe
      set proved to have a 100 % analytical specificity and a sensitivity of 1.8 ag
      MUl(-1), equivalent to 1.7 colony-forming units (CFU) ml(-1), for purified DNA,
      3.4 CFU g(-1) for seeded liver, kidney, and spleen tissues, and 0.34 CFU/100 MUl(
      1) for seeded blood, respectively. The assay was highly reproducible with low
      variation coefficient values for intra- and inter-run experiments (2.9 % and 9.5
      %, respectively). Following optimization, the assay was used to detect changes in
      the bacterial load during experimental infection. Rainbow trout (Onchorhynchus
      mykiss) were exposed to two strains of Y. ruckeri (biotype 1 and biotype 2) by
      intraperitoneal inoculation. Internal organs (liver, kidney, spleen) and blood
      were biopsied from dead fish daily for 15 days to quantify copies of pathogen DNA
      per gram of tissue. The findings showed the efficacy of this real-time PCR assay
      to quantify Y. ruckeri cells in the fish tissues and also confirmed this assay as
      a non-lethal method for the detection of this pathogen in blood samples.

PMID- 22868828
TI  - A decrease in diet quality occurs during pregnancy in overweight and obese women
      which is maintained post-partum.
AB  - BACKGROUND: Ensuring adequate dietary intake during pregnancy has important
      implications for optimising maternal and fetal health. It is not known whether
      diet quality is altered over pregnancy and the post-partum period. OBJECTIVE: The
      aim of this study was to perform a comprehensive assessment of diet quality in
      overweight and obese women during pregnancy and early post-partum. DESIGN: In a
      prospective cohort study, n=301 overweight or obese pregnant women completed a
      food frequency questionnaire at study entry (10-20 weeks gestation), 28 weeks
      gestation, 36 weeks gestation and 4 months post-partum for assessment of
      macronutrient and micronutrient intake and diet quality by the Healthy Eating
      Index (HEI). RESULTS: Energy, macronutrient and dietary sources of micronutrients
      did not alter across pregnancy or post-partum. The HEI was of below average
      quality in 31.0% of women at baseline. This decreased from week 28 (P<0.001) and
      was maintained at a lower level post-partum such that HEI levels were lower
      compared with study entry (53.3+/-12.7 versus 56.7+/-10.1, P<0.001). The HEI
      decrease occurred in association with decreases in the milk, meat and unsaturated
      oil components, and increases in the proportion of energy from solid fats,
      alcohol and added sugars (P<0.001), and was independently predicted by the
      socioeconomic index for areas score (beta=-0.011, s.e.=0.011, P=0.031).
      CONCLUSION: We report for the first time that dietary quality decreases across
      pregnancy and is maintained at this reduced level in the early post-partum period
      in overweight and obese women. Dietary interventions aimed at improving diet
      quality should be targeted to early pregnancy and post-partum.

PMID- 22868829
TI  - High fat/carbohydrate ratio but not total energy intake induces lower striatal
      dopamine D2/3 receptor availability in diet-induced obesity.
AB  - High-energy diets that induce obesity decrease striatal dopamine D2/3 receptor
      (DRD2/3) availability. It is however poorly understood which components of these
      diets are underlying this decrease. This study assessed the role of saturated fat
      intake on striatal DRD2/3 availability. Forty rats were randomized to a free
      choice high-fat high-sugar diet (HFHS) or a standard chow diet for 28 days.
      Striatal DRD2/3 availability was measured using (123)I-IBZM storage phosphor
      imaging at day 29. The HFHS group was split in a HFHS-high-fat (HFHS-hf) and HFHS
      low-fat (HFHS-lf) group based on the percentage energy intake from fat. Rats of
      both HFHS subgroups had increased energy intake, abdominal fat stores and plasma
      leptin levels compared with controls. DRD2/3 availability in the nucleus
      accumbens (NAcc) was significantly lower in HFHS-hf than in HFHS-lf rats, whereas
      it was similar for HFHS-lf and control rats. Furthermore, DRD2/3 availability in
      the NAcc was positively correlated with the percentage energy intake from sugar.
      Total energy intake was lower for HFHS-hf than for HFHS-lf rats. Together these
      results suggest that a diet with a high fat/carbohydrate ratio, but not total
      energy intake or the level of adiposity, is the best explanation for the decrease
      in striatal DRD2/3 availability observed in diet-induced obesity.

PMID- 22868830
TI  - Endocannabinoids regulate adipokine production and the immune balance of omental
      adipose tissue in human obesity.
AB  - OBJECTIVES: (1) To investigate whether modulation of the cannabinoid type 1
      receptor (CB1R) directly regulates the production of adiponectin (ApN) and other
      adipokines in omental adipose tissue (OAT) of obese subjects, (2) to establish in
      which cellular fraction of OAT the effects of CB1R blockade take place and (3) to
      unravel the underlying mechanisms. SUBJECTS AND METHODS: OAT was obtained from 30
      obese subjects (body mass index: 40.6+/-1.3 kg m(-2)) undergoing abdominal
      surgery. Primary cultures of explants or of freshly isolated adipocytes or
      stromal-vascular cells (SVCs) were used. RESULTS: In OAT explants, the CB1R
      blocker Rimonabant upregulated ApN gene expression. mRNA abundance of omentin
      that exhibits insulin-sensitizing properties was upregulated as well. Conversely,
      mRNA levels of two pro-inflammatory cytokines, macrophage inflammatory protein
      (MIP)-1beta and interleukin (IL)-7 were downregulated. We next examined where
      these effects took place within OAT. CB1R expression was similar in both cellular
      fractions. In isolated mature adipocytes, blockade of CB1R reproduced the
      increase of ApN mRNA and the decrease of IL-7 mRNA, while inducing a rise of ApN
      secretion into the medium. In isolated SVC, gene expression of omentin, which is
      restricted to this fraction, was augmented, while that of MIP-1beta was
      diminished. Finally, we deciphered the mechanisms leading to ApN regulation by
      the endocannabinoid system (ES). We first established that ApN regulation was
      actually mediated by the CB1R: ApN gene expression was upregulated by Rimonabant
      and downregulated by the CB1R agonist arachidonyl-2-chloroethylamide (ACEA).
      Upregulation of ApN by Rimonabant was unaltered by inhibiting cAMP production.
      However, downregulation of ApN by ACEA was fully reversed by an inhibitor of p38
      mitogen-activated protein kinase (p38MAPK) and ACEA increased p38MAPK
      phosphorylation. CONCLUSIONS: Blockade of CB1R attenuates the inflammatory state
      in both cellular fractions of OAT either by increasing ApN and omentin production
      or by decreasing mRNAs of MIP-1beta and IL-7. ApN regulation by the ES partly
      involves p38MAPK.

PMID- 22868831
TI  - Identification of a dietary pattern prospectively associated with increased
      adiposity during childhood and adolescence.
AB  - BACKGROUND: Specific dietary risk factors for excess adiposity in young people
      are poorly understood. However, studies in adults suggest dietary energy density,
      fat and fibre are critical dietary factors. OBJECTIVE: To examine longitudinal
      relationships between a dietary pattern (DP) characterised by dietary energy
      density, % total energy from fat and fibre density and fat mass (FM) in children
      from 7 to 15 years of age. DESIGN: Subjects were 6772 children from the UK Avon
      Longitudinal Study of Parents and Children. Dietary intake was assessed using a 3
      day food diary at 7, 10 and 13 years of age. An energy-dense, high-fat, low-fibre
      DP was identified using reduced rank regression and subjects scored for the DP at
      each age. FM was measured at 11, 13 and 15 years and FM index (FMI) calculated as
      FM/height((x)). Longitudinal models were adjusted for dietary misreporting,
      physical activity and maternal factors. RESULTS: DP z-scores at all ages were
      positively associated with later FMI. A 1 s.d. unit increase in DP z-score was
      longitudinally associated with an average increase in FMI z-score of 0.04 s.d.
      units (95% confidence interval (CI), 0.01-0.07). For each 1 s.d. unit increase in
      DP z-score, the odds of being in the highest quintile for FMI (as a marker of
      excess adiposity) increased by 13% (95% CI, 1-27%). CONCLUSIONS: Dietary habits
      during childhood are associated with increased adiposity in adolescence, with
      specific implications for dietary energy density, fat and fibre intake. Improving
      diet quality may reduce the risk of obesity in young people.

PMID- 22868832
TI  - Should the hemoglobin A1c diagnostic cutoff differ between blacks and whites? A
      cross-sectional study.
AB  - BACKGROUND: Hemoglobin A1c (HbA1c) levels are known to be consistently higher in
      black persons than in white persons at any given glycemic level. Whether the
      optimal diagnostic threshold of HbA1c should differ between blacks and whites is
      unclear. OBJECTIVE: To compare the relationships between HbA1c level and the
      prevalence of retinopathy in black and white U.S. adults. DESIGN: Cross-sectional
      study. SETTING: A nationally representative sample of the National Health and
      Nutrition Examination Survey from 2005 through 2008. PATIENTS: 2804 white persons
      and 1008 black persons aged 40 years or older in the United States. MEASUREMENTS:
      Prevalence of retinopathy. Logistic regression models and restricted cubic spline
      models were constructed separately for white and black populations to test the
      HbA1c levels at which risk for retinopathy begins to increase. RESULTS: After
      adjustment for age, sex, hypertension, body mass index, family history of
      diabetes, and use of antidiabetes medications or insulin, the lowest HbA1c
      category for which the prevalence of retinopathy was significantly higher than
      the reference category (<5.5%) was 6.0% to 6.4% for white persons (risk
      difference, 4.8% [95% CI, 0.5% to 9.1%]) and 5.5% to 5.9% for black persons (risk
      difference, 5.3% [CI, 1.0% to 9.5%]). The restricted cubic spline models
      indicated that the risk for retinopathy increased at lower HbA1c levels in black
      persons than in white persons. LIMITATION: The cross-sectional design of the
      study precluded examining the effect of the duration at each HbA1c level.
      CONCLUSION: The prevalence of retinopathy begins to increase at a lower HbA1c
      level in black Americans than in white Americans. The findings do not support
      increasing the diagnostic threshold of HbA1c in black persons. PRIMARY FUNDING
      SOURCE: None.

PMID- 22868833
TI  - The influence of context on antimicrobial prescribing for febrile respiratory
      illness: a cohort study.
AB  - BACKGROUND: Little is known about the influence of contextual factors on a
      physician's likelihood to prescribe antimicrobials for febrile respiratory
      illness (FRI). Context includes epidemiologic context (for example, a pandemic
      period) and personal context (for example, recent exposure to other patients with
      FRI). OBJECTIVE: To examine the association between contextual factors and
      antimicrobial prescribing for FRI. DESIGN: 5.5-year retrospective cohort study.
      SETTING: A network of Midwestern primary care providers. PATIENTS: All patients
      presenting with FRI during influenza seasons between 2006 and 2011. MEASUREMENTS:
      Antimicrobial prescribing for FRI during pandemic and seasonal influenza periods.
      RESULTS: 28 301 unique patient encounters for FRI with 69 physicians in 26
      practices were included. An antibiotic was prescribed in 12 795 (45.2%) cases.
      The range of prescribing among physicians was 17.9% to 83.7%. Antibiotics were
      prescribed in 47.5% of encounters during the seasonal period and 39.2% during the
      pandemic period (P < 0.001). After multivariable adjustment for patient and
      physician characteristics, antibiotic prescribing was lower in the pandemic
      period (odds ratio [OR], 0.72 [95% CI, 0.68 to 0.77]) than in the seasonal
      period. The likelihood of prescribing an antibiotic decreased as the number of
      FRI cases that a physician had seen in the previous week increased (OR, 0.93 [CI,
      0.86 to 1.01] for 2 to 3 patients with FRI seen in the previous week; OR, 0.84
      [CI, 0.77 to 0.91] for 4 to 6 patients; OR, 0.71 [CI, 0.64 to 0.78] for 7 to 11
      patients; and OR, 0.57 [CI, 0.51 to 0.63] for >=12 patients compared with the
      reference range of 0 to 1 patients). Pandemic season and recent personal context
      were also associated with antiviral prescribing. LIMITATION: Retrospective study
      in a single geographic area. CONCLUSION: Epidemiologic context and the number of
      cases of FRI that a physician had recently seen were associated with his or her
      likelihood to prescribe antimicrobials for FRI. Interventions that enhance a
      physician's contextual awareness may improve antimicrobial use. PRIMARY FUNDING
      SOURCE: NorthShore University HealthSystem.

PMID- 22868834
TI  - Sleep disruption due to hospital noises: a prospective evaluation.
AB  - BACKGROUND: Sleep plays a critical role in maintaining health and well-being;
      however, patients who are hospitalized are frequently exposed to noise that can
      disrupt sleep. Efforts to attenuate hospital noise have been limited by
      incomplete information on the interaction between sounds and sleep physiology.
      OBJECTIVE: To determine profiles of acoustic disruption of sleep by examining the
      cortical (encephalographic) arousal responses during sleep to typical hospital
      noises by sound level and type and sleep stage. DESIGN: 3-day polysomnographic
      study. SETTING: Sound-attenuated sleep laboratory. PARTICIPANTS: Volunteer sample
      of 12 healthy participants. INTERVENTION: Baseline (sham) night followed by 2
      intervention nights with controlled presentation of 14 sounds that are common in
      hospitals (for example, voice, intravenous alarm, phone, ice machine, outside
      traffic, and helicopter). The sounds were administered at calibrated, increasing
      decibel levels (40 to 70 dBA [decibels, adjusted for the range of normal
      hearing]) during specific sleep stages. MEASUREMENTS: Encephalographic arousals,
      by using established criteria, during rapid eye movement (REM) sleep and non-REM
      (NREM) sleep stages 2 and 3. RESULTS: Sound presentations yielded arousal
      response curves that varied because of sound level and type and sleep stage.
      Electronic sounds were more arousing than other sounds, including human voices,
      and there were large differences in responses by sound type. As expected, sounds
      in NREM stage 3 were less likely to cause arousals than sounds in NREM stage 2;
      unexpectedly, the probability of arousal to sounds presented in REM sleep varied
      less by sound type than when presented in NREM sleep and caused a greater and
      more sustained elevation of instantaneous heart rate. LIMITATIONS: The study
      included only 12 participants. Results for these healthy persons may
      underestimate the effects of noise on sleep in patients who are hospitalized.
      CONCLUSION: Sounds during sleep influence both cortical brain activity and
      cardiovascular function. This study systematically quantifies the disruptive
      capacity of a range of hospital sounds on sleep, providing evidence that is
      essential to improving the acoustic environments of new and existing health care
      facilities to enable the highest quality of care. PRIMARY FUNDING SOURCE: Academy
      of Architecture for Health, Facilities Guidelines Institute, and The Center for
      Health Design.

PMID- 22868835
TI  - Viscosupplementation for osteoarthritis of the knee: a systematic review and meta
      analysis.
AB  - BACKGROUND: Viscosupplementation, the intra-articular injection of hyaluronic
      acid, is widely used for symptomatic knee osteoarthritis. PURPOSE: To assess the
      benefits and risks of viscosupplementation for adults with symptomatic knee
      osteoarthritis. DATA SOURCES: MEDLINE (1966 to January 2012), EMBASE (1980 to
      January 2012), the Cochrane Central Register of Controlled Trials (1970 to
      January 2012), and other sources. STUDY SELECTION: Randomized trials in any
      language that compared viscosupplementation with sham or nonintervention control
      in adults with knee osteoarthritis. DATA EXTRACTION: Primary outcomes were pain
      intensity and flare-ups. Secondary outcomes included function and serious adverse
      events. Reviewers used duplicate abstractions, assessed study quality, pooled
      data by using a random-effects model, examined funnel plots, and explored
      heterogeneity by using meta-regression. DATA SYNTHESIS: Eighty-nine trials
      involving 12 667 adults met inclusion criteria. Sixty-eight had a sham control,
      40 had a follow-up duration greater than 3 months, and 22 used cross-linked forms
      of hyaluronic acid. Overall, 71 trials (9617 patients) showed that
      viscosupplementation moderately reduced pain (effect size, -0.37 [95% CI, -0.46
      to -0.28]). There was important between-trial heterogeneity and an asymmetrical
      funnel plot: Trial size, blinded outcome assessment, and publication status were
      associated with effect size. Five unpublished trials (1149 patients) showed an
      effect size of -0.03 (CI, -0.14 to 0.09). Eighteen large trials with blinded
      outcome assessment (5094 patients) showed a clinically irrelevant effect size of 
      0.11 (CI, -0.18 to -0.04). Six trials (811 patients) showed that
      viscosupplementation increased, although not statistically significantly, the
      risk for flare-ups (relative risk, 1.51 [CI, 0.84 to 2.72]). Fourteen trials
      (3667 patients) showed that viscosupplementation increased the risk for serious
      adverse events (relative risk, 1.41 [CI, 1.02 to 1.97]). LIMITATIONS: Trial
      quality was generally low. Safety data were often not reported. CONCLUSION: In
      patients with knee osteoarthritis, viscosupplementation is associated with a
      small and clinically irrelevant benefit and an increased risk for serious adverse
      events. PRIMARY FUNDING SOURCE: Arco Foundation.

PMID- 22868836
TI  - Update in nephrology: evidence published in 2011.

PMID- 22868837
TI  - Prevention of falls in community-dwelling older adults: U.S. Preventive Services
      Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 1996 U.S. Preventive Services Task Force (USPSTF)
      recommendation statement on counseling to prevent household and recreational
      injuries, including falls. METHODS: The USPSTF reviewed new evidence on the
      effectiveness and harms of primary care-relevant interventions to prevent falls
      in community-dwelling older adults. The interventions were grouped into 5 main
      categories: multifactorial clinical assessment (with or without direct
      intervention), clinical management (with or without screening), clinical
      education or behavioral counseling, home hazard modification, and exercise or
      physical therapy. RECOMMENDATIONS: The USPSTF recommends exercise or physical
      therapy and vitamin D supplementation to prevent falls in community-dwelling
      adults aged 65 years or older who are at increased risk for falls. (Grade B
      recommendation)The USPSTF does not recommend automatically performing an in-depth
      multifactorial risk assessment in conjunction with comprehensive management of
      identified risks to prevent falls in community-dwelling adults aged 65 years or
      older because the likelihood of benefit is small. In determining whether this
      service is appropriate in individual cases, patients and clinicians should
      consider the balance of benefits and harms on the basis of the circumstances of
      prior falls, comorbid medical conditions, and patient values. (Grade C
      recommendation).

PMID- 22868838
TI  - Federal plan for prescriber education on opioids misses opportunities.

PMID- 22868839
TI  - Implementing the learning health system: from concept to action.
AB  - Clinicians and health systems are facing widespread challenges, including changes
      in care delivery, escalating health care costs, and the need to keep up with
      rapid scientific discovery. Reorganizing U.S. health care and changing its
      practices to render better, more affordable care requires transformation in how
      health systems generate and apply knowledge. The "rapid-learning health system"
      posited as a conceptual strategy to spur such transformation-leverages recent
      developments in health information technology and a growing health data
      infrastructure to access and apply evidence in real time, while simultaneously
      drawing knowledge from real-world care-delivery processes to promote innovation
      and health system change on the basis of rigorous research. This article
      describes an evolving learning health system at Group Health Cooperative, the 6
      phases characterizing its approach, and examples of organization-wide
      applications. This practical model promotes bidirectional discovery and an open
      mind at the system level, resulting in willingness to make changes on the basis
      of evidence that is both scientifically sound and practice-based. Rapid learning
      must be valued as a health system property to realize its full potential for
      knowledge generation and application.

PMID- 22868840
TI  - The context of antibiotic overuse.

PMID- 22868841
TI  - Translating the fall prevention recommendations into a covered service: can it be
      done, and who should do it?

PMID- 22868842
TI  - A balancing act.

PMID- 22868844
TI  - Screening for colorectal cancer.

PMID- 22868845
TI  - Screening for colorectal cancer.

PMID- 22868846
TI  - Screening for colorectal cancer.

PMID- 22868848
TI  - Overdiagnosis of Invasive Breast Cancer due to Mammography Screening.

PMID- 22868849
TI  - Overdiagnosis of invasive breast cancer due to mammography screening.

PMID- 22868850
TI  - Overdiagnosis of invasive breast cancer due to mammography screening.

PMID- 22868851
TI  - Overdiagnosis of invasive breast cancer due to mammography screening.

PMID- 22868853
TI  - Long-delayed localization of a cardiac functional paraganglioma with SDHC
      mutation.

PMID- 22868855
TI  - Summaries for patients. Sleep disruption due to hospital noises.

PMID- 22868856
TI  - Summaries for patients. Preventing falls in older adults who live in community
      settings: U.S. Preventive Services Task Force recommendation.

PMID- 22868857
TI  - Summaries for patients. Viscosupplementation for knee osteoarthritis.

PMID- 22868858
TI  - In the clinic. Lyme disease.

PMID- 22868860
TI  - Alzheimer disease: Florbetapir-a useful tool to image amyloid load and predict
      cognitive decline in Alzheimer disease.

PMID- 22868861
TI  - Traumatic brain injury: CT scan does not predict outcome of mild traumatic brain
      injury.

PMID- 22868864
TI  - Epilepsy: Update to guidelines on treatment of infantile spasms.

PMID- 22868866
TI  - Multiple sclerosis: Cognitive training provides lasting benefits for patients
      with multiple sclerosis.

PMID- 22868867
TI  - Stroke: Treatment for acute stroke--the end of the citicoline saga.

PMID- 22868869
TI  - Quercetin-3-O-glucuronide affects the gene expression profile of M1 and M2a human
      macrophages exhibiting anti-inflammatory effects.
AB  - Due to their recently discovered plasticity, macrophages could be an important
      target in the treatment and prevention of atherosclerosis, and it is of interest
      that quercetin has been shown to modulate inflammation in humans through
      mechanisms involving macrophages. The aim of this work was to investigate the
      effect of quercetin-3-O-glucuronide (Q3GA), a major circulating human metabolite
      of quercetin, on gene expression in differently polarized human macrophages.
      Classical (M1) and alternative (M2a) macrophages were exposed to Q3GA (500 nM).
      Gene expression was monitored after incubation periods of 6, 12 and 24 h. M1 and
      M2a macrophages maintained their respective traits. Q3GA did not affect M1
      macrophages in the promotion of a defense response, which remains the principal
      characteristic of this type of activation, but it was able to reduce the
      transcription of genes involved in inflammation, such as pro-inflammatory
      interleukins and enzymes involved in oxidative stress responses. Exposure of M2a
      to Q3GA elicited an improvement in anti-inflammatory features resulting from
      further down-regulation of pro-inflammatory genes. Thus, Q3GA is a potential anti
      atherogenic metabolite, enhancing the anti-inflammatory properties of M2a
      macrophages and modulating immune response effects in the presence of pro
      inflammatory stimuli.

PMID- 22868868
TI  - EEG source imaging in epilepsy--practicalities and pitfalls.
AB  - EEG source imaging (ESI) is a model-based imaging technique that integrates
      temporal and spatial components of EEG to identify the generating source of
      electrical potentials recorded on the scalp. Recent advances in computer
      technologies have made the analysis of ESI data less time-consuming, and have
      rekindled interest in this technique as a clinical diagnostic tool. On the basis
      of the available body of evidence, ESI seems to be a promising tool for epilepsy
      evaluation; however, the precise clinical value of ESI in presurgical evaluation
      of epilepsy and in localization of eloquent cortex remains to be investigated. In
      this Review, we describe two fundamental issues in ESI; namely, the forward and
      inverse problems, and their solutions. The clinical application of ESI in
      surgical planning for patients with medically refractory focal epilepsy, and its
      use in source reconstruction together with invasive recordings, is also
      discussed. As ESI can be used to map evoked responses, we discuss the clinical
      utility of this technique in cortical mapping-an essential process when planning
      resective surgery for brain regions that are in close proximity to eloquent
      cortex.

PMID- 22868870
TI  - Symptomatic intracranial hemorrhage following intravenous thrombolysis for acute
      ischemic stroke: a critical review of case definitions.
AB  - BACKGROUND: Symptomatic intracranial hemorrhage (SICH) is a devastating
      complication of intravenous thrombolysis treatment that is associated with high
      mortality. Clinical trials, stroke registries and cohort studies employ different
      case definitions to identify stroke patients with SICH following intravenous
      thrombolysis. We systematically reviewed the reported rates of SICH following
      intravenous thrombolysis and compared their consistency with mortality outcomes.
      METHODS: Studies were identified from the PubMed and Embase databases from
      January 1994 to July 2011 by cross-referencing the following MeSH terms:
      'thrombolysis', 'recombinant tissue plasminogen activator', 'rtPA', 'hemorrhagic
      stroke', 'cerebral hemorrhage', 'hematoma' and 'ischemic stroke'. Demographic
      information, baseline National Institute of Health Stroke Scale (NIHSS) scores,
      time from stroke onset to intravenous thrombolysis, SICH and mortality rates were
      derived from published data in 7 randomized controlled trials, 7 stroke
      registries and 10 cohort studies (4 multicenter and 6 single center) with more
      than 200 consecutively recruited patients. Mortality rates were considered as the
      percentage of patients treated with intravenous thrombolysis who died within 90
      days after stroke. RESULTS: The mean age of patients included in this analysis
      was 68.8 years (standard deviation, SD 2.9, range 63-75), of whom 56.3% (SD 4.5,
      range 45-63) were men. They presented with a mean baseline NIHSS of 12.5 (SD 1.4,
      range 9-15) and received intravenous thrombolysis 175 min (SD 62, range 120-328)
      from stroke onset. The overall mean SICH and mortality rates of patients treated
      with intravenous thrombolysis were 5.6% (SD 2.3) and 14.7% (SD 4.8),
      respectively. A moderate correlation was observed between the incidence of SICH
      and mortality in patients treated with intravenous thrombolysis (r = 0.401, p =
      0.050). The variation in SICH rates was highest across studies that reported SICH
      rates using the Safe Implementation of Thrombolysis in Stroke-Monitoring Study
      (SITS-MOST) criteria compared with the European Cooperative Acute Stroke Study
      and National Institute of Neurological Disorders and Stroke (NINDS) criteria.
      Studies that defined SICH as parenchymal hemorrhage with a neurological decline
      NIHSS >=4 occurring within 36 h of intravenous thrombolysis reported a higher
      consistency between SICH and mortality rates (correlation coefficient 0.631).
      CONCLUSIONS: SICH rates vary considerably between studies and these differences
      may relate to the differences in the criteria used to define SICH. Until a case
      definition with high interrater agreement and good correlation with stroke
      outcomes becomes available, detailed information on the type of bleeding, the
      extent of NIHSS deterioration, neuroimaging features and the time from
      thrombolysis to diagnosis of hemorrhage should be reported to permit a correct
      interpretation of SICH rates.

PMID- 22868871
TI  - Improving diabetes care for young people with type 1 diabetes through visual
      learning on mobile phones: mixed-methods study.
AB  - BACKGROUND: Only 17% of Norwegian children and adolescents with diabetes achieve
      international treatment goals measured by glycated hemoglobin (HbA(1c)). Classic
      patient-physician consultations seem to be poorly adapted to young children. New
      strategies that are better attuned to young people to improve support of
      adolescents' self-management of diabetes need to be tested and evaluated.
      OBJECTIVE: (1) To explore how applications for mobile phones can be used in
      follow-up of adolescents with type 1 diabetes, and (2) to use the findings to
      guide further development of the applications and as a basis for future studies.
      METHOD: We pilot tested two mobile phone applications: (1) an application that
      contained a picture-based diabetes diary to record physical activity and photos
      taken with the phone camera of food eaten, where the phone also communicated with
      the glucometer by Bluetooth technology to capture blood glucose values, and (2) a
      Web-based, password-secured and encrypted short message service (SMS), based on
      access using login passwords received via SMS to be used by participants to send
      messages to their providers when they faced obstacles in everyday life, and to
      send educational messages to the participants. At the end of the 3-month pilot
      study, 12 participants (7 girls and 5 boys ) aged 13-19 years completed
      semistructured interviews. The participants had a mean HbA(1c )value of 8.3 (SD
      0.3), mean age of 16.2 (SD 1.7) years, mean body mass index of 23.3 (SD 3.2)
      kg/m(2), and mean diabetes duration of 7.5 (SD 4.6) years. We applied three
      additional measurements: change in metabolic control as measured by HbA(1c), the
      System Usability Scale, and diabetes knowledge. RESULTS: From the interviews,
      three main categories emerged: visualization, access, and software changes.
      Participants appreciated the picture-based diary more than the SMS solution.
      Visualization of cornerstones in diabetes self-care (ie, diet, insulin dosage,
      physical activity, and pre- and postprandial glucose measurements all transformed
      into one picture) in the mobile diary was found to be an important educational
      tool through reflections in action. This led to a change in participants' applied
      knowledge about the management of their disease. Additional measurements
      supplemented and supported the qualitative findings. However, changes in HbA(1c
      )and participants' theoretical knowledge as tested by a 27-item questionnaire,
      based on a national health informatics' diabetes quiz, before and after the
      intervention were not statistically significant (P = .38 and P = .82,
      respectively, paired-samples t test). Participants suggested additional
      functionality, and we will implement this in the design of the next software
      generation. CONCLUSION: Participants reported an increased understanding of
      applied knowledge, which seem to positively affect diabetes self-care. Visual
      impressions seem well adapted to the maturation of the adolescent brain,
      facilitating the link between theoretical knowledge and executive functions. SMS
      gave the adolescents a feeling of increased access and security. Participants
      gave valuable input for further development of these applications.

PMID- 22868877
TI  - Improvement of brain reward abnormalities by antipsychotic monotherapy in
      schizophrenia.
AB  - CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine
      neurotransmission and the brain reward system. However, it remains unclear
      whether antipsychotic treatment, which blocks dopamine transmission, improves,
      alters, or even worsens the reward-related abnormalities. OBJECTIVE To
      investigate changes in reward-related brain activations in schizophrenia before
      and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN
      Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the
      Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic-naive patients
      with first-episode schizophrenia and 24 healthy controls initially matched on
      age, sex, and parental socioeconomic status were examined with functional
      magnetic resonance imaging while playing a variant of the monetary incentive
      delay task. INTERVENTIONS Patients were treated for 6 weeks with the
      antipsychotic compound amisulpride. Controls were followed up without treatment.
      MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as
      measured by functional magnetic resonance imaging before and after antipsychotic
      treatment. RESULTS At baseline, patients, as compared with controls, demonstrated
      an attenuation of brain activation during reward anticipation in the ventral
      striatum, bilaterally. After 6 weeks of treatment, patients showed an increase in
      the anticipation-related functional magnetic resonance imaging signal and were no
      longer statistically distinguishable from healthy controls. Among the patients,
      there was a correlation between the improvement of positive symptoms and
      normalization of reward-related activation. Those who showed the greatest
      clinical improvement in positive symptoms also showed the greatest increase in
      reward-related activation after treatment. CONCLUSIONS To our knowledge, this is
      the first controlled, longitudinal study of reward disturbances in schizophrenic
      patients before and after their first antipsychotic treatment. Our results
      demonstrate that alterations in reward processing are fundamental to the illness
      and are seen prior to any treatment. Antipsychotic treatment tends to normalize
      the response of the reward system; this was especially seen in the patients with
      the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION
      clinicaltrials.gov Identifier: NCT01154829.

PMID- 22868876
TI  - Systematic, evidence-based discovery of biomarkers at the NCI.
AB  - In the past decade, biomarker discovery has become ubiquitous in cancer research.
      However, despite this interest in biomarker research, few newly-characterized
      biomarkers have emerged as clinically-used entities. Here, we review the current
      state of biomarker research in cancer and identify challenges that stall many
      biomarker discovery efforts. We outline a model for systematic biomarker
      discovery, exemplified by recent efforts in prostate cancer, in which
      bioinformatics plays a central role in identifying promising new candidate
      biomarkers. Finally, we review the role of the National Cancer Institute's Early
      Detection Research Network (EDRN) in biomarker studies and the importance of EDRN
      led efforts to establish a research standard for more effective biomarker
      discovery efforts.

PMID- 22868878
TI  - [Neuronal linkage of the cerebral cortex and the striatum].
AB  - The striatum is the major input station of the basal ganglia. It receives a wide
      variety of inputs from all areas of the cerebral cortex. In particular, there are
      several parallel loop circuits, such as the motor, oculomotor, dorsolateral
      prefrontal, lateral orbitofrontal, and anterior cingulate loops, linking the
      frontal lobe and the basal ganglia. With respect to the motor loop, the motor
      related areas, including the primary motor cortex, supplementary motor area,
      dorsal and ventral premotor cortices, presupplementary motor area, and rostral
      and caudal cingulate motor areas, send inputs to sectors of the putamen in
      combination via separate (parallel) and overlapping (convergent) pathways. Such
      signals return to the cortical areas of origin via the globus pallidus/substantia
      nigra and then the thalamus. The somatotopical representation is maintained in
      each structure that constitutes the motor loop. Employing retrograde
      transsynaptic transport of rabies virus, we have recently investigated the
      arrangement of multisynaptic pathways linking the basal ganglia to the caudal
      aspect of the dorsal premotor cortex (the so-called F2). F2r, the rostral sector
      of F2, has been shown to be involved in motor planning, whereas F2c, the caudal
      sector of F2, has been shown to be involved in motor execution. We analyzed the
      origins of multisynaptic inputs to F2r and F2c in the basal ganglia. Our results
      indicate that the 2 loop circuits connecting the F2r and F2c with the basal
      ganglia may possess a common convergent window at the input stage, while they
      have parallel divergent channels at the output stage.

PMID- 22868879
TI  - [Optogenetic analysis of striatal circuits].
AB  - The striatum receives inputs from both cortical and subcortical structures,
      reflecting the role of the striatum as a limbic-motor interface. The relative
      simplicity of the cellular architecture of the striatum belies the complexity of
      the circuitry. Because synaptic inputs are intermingled, using classical methods
      to selectively activate or inhibit known populations of neurons has not been
      possible. The advent of optogenetics has enabled population-selective activation
      or inhibition in intact animals. In this review, I describe how optogenetic
      analysis can be used to study striatal circuits. First, I briefly introduce
      optogenetics and the widely used channelrhodopsin for excitation and
      halorhodopsin for inhibition. Next, I categorize optogenetic studies based on the
      approaches optogenetics have made possible, specifically (1) selective activation
      of identified synaptic inputs, (2) activation of convergent inputs to identify
      weak synaptic connections, (3) selective activation of identified neuronal
      populations in freely moving animals, and (4) cell identification for in vivo
      recording, and I discuss new insights into striatal circuits. Optogenetic
      approaches made impossible experiments possible and help to resolve the function
      of intact brain circuitry.

PMID- 22868880
TI  - [Value representation in the striatum and prefrontal cortex].
AB  - To survive under changing circumstances, we have to make appropriate decisions on
      our behavior. For this purpose, the brain should recognize reward information
      from objects under a given circumstances. Recent experimental and theoretical
      studies have suggested that primates, including human beings, have at least 2
      brain processes that calculate the reward value of objects. One is the process
      coding a specific reward value of a stimulus or response, depending on direct
      experience (e.g., classical conditioning and TD learning). The other enables us
      to predict reward based on the internal model of given circumstances without
      direct experience (e.g., categorization and inference). To clarify the neuronal
      correlates of the multiple processes on reward prediction, we have conducted 4
      experiments: (1) single-unit recording from the caudate and lateral prefrontal
      cortex of a monkey, while it performed a memory-guided saccade task with
      asymmetric reward schedule; (2) human fMRI imaging during random-dot
      discrimination with asymmetric reward condition; (3) single-unit recording from
      the monkey dopamine neuron in the random-dot discrimination task with asymmetric
      reward schedule; and (4) simultaneous single-unit recording from the striatum and
      lateral prefrontal cortex of monkeys performing a reward inference task. Results
      suggest that the nigro striatal network and the prefrontal network have different
      functional roles for reward prediction (value generation). The former applies the
      model-free method (temporal-difference learning), while the latter uses the model
      based method (category-based learning).

PMID- 22868881
TI  - [Challenge to understand the neurobiology of obsessive-compulsive disorder].
AB  - Obsessive-compulsive disorder (OCD) is characterized by obsession (recurrent
      intrusive thoughts) and compulsion (repetitive behaviors or mental acts). There
      is no consensus regarding the pathogenesis of OCD, which could support the idea
      that this disorder is heterogeneous. However, functional imaging data and
      surgical findings in humans suggest that the hyperactivity of the specific
      circuit including the striatum, called the cortico-striato-thalamo-cortical
      circuit, plays a role in OCD pathogenesis. Recently, validated animal models of
      OCD have been established, and they provide us the opportunity to address how the
      altered functional activity of this circuit contributes to the repetitive
      behavior in OCD. To test the causal relationship between the altered function of
      the circuit and behavioral abnormalities in animals, cell-type-specific
      manipulation and detection of changes in the circuit will be required.
      Optogenetic approaches may be used as tools to dissect the complex circuit.
      Moreover, mouse functional magnetic resonance imaging may yield data comparable
      to human imaging data.

PMID- 22868882
TI  - [The role of the striatum in addiction].
AB  - Addiction is a notorious treatment-resistant psychiatric disorder characterized
      by the impairment of self-monitoring, loss of interest in other targets of
      pleasure, and uncorrectable impulsive/compulsive drug-seeking behaviors. The
      striatum, particularly the ventral striatum (= the nucleus accumbens) is deeply
      involved in the acquisition and expression of addiction. Although only few
      pharmacotherapeutic approaches against addiction are available, the currently
      used animal models of addiction are sophisticated enough to mimic most of the
      representative phenotypes observed in human addicts. In addition, recent advances
      in neuroimaging techniques, such as positron emission tomography or functional
      magnetic resonance imaging, as well as computational neuroscience approaches have
      promoted our understanding of addiction, particularly at the circuitry level. In
      this review, I introduce some pivotal topics regarding addiction for discussion.
      First, I outline the updated concept regarding how dopamine is involved in
      addiction by focusing on 2 seemingly uncompromising hypotheses, prediction-error
      theory and incentive salience theory. Second, after providing a brief
      introduction to unmanageable maladaptive behaviors in addiction that may be
      attributable to the impairments of the medial prefrontal cortex, anterior
      cingulate cortex, and orbitofrontal cortex, I emphasize the roles of
      glutamatergic inputs projecting from these frontal areas to the nucleus accumbens
      in cue-primed reinstatement of drug-seeking and impaired neuronal plasticity.
      Third, on the basis of the complementary or counterbalancing relationship between
      goal-directed behaviors and habits, I discuss the foresights and pitfalls of the
      current concept of "addiction as a pathological habit." Lastly, I conclude my
      discussion with an integrated (but a rough) circuitry model of addiction.

PMID- 22868883
TI  - [Roles of altered striatal function in major depression].
AB  - Major depression, a psychiatric disorder characterized by depressive mood and
      loss of interest and pleasure, is a leading cause of disability and suicide in
      developed countries. However, the mechanisms that underlie major depression
      remain to be elucidated. Clinical studies on patients with major depression have
      shown abnormalities in multiple brain areas, each of which can account for a
      distinct symptom or endophenotype. Notably, the striatum in healthy control
      subjects responds to positive emotional stimuli and to positive feedback signals
      during cognitive tasks, but these striatal responses are greatly reduced in
      depressive patients. Given the role of the striatum in behavioral learning with
      positive reinforcers, abnormalities as such suggest that impairment in reward
      processing and/or reinforcement learning in major depression is the basis of
      anhedonia and reduced psychomotor activity. In animal studies, stress -a risk
      factor for major depression- is frequently used to induce behavioral depression.
      Repeated social defeat stress increases the excitability of dopamine neurons and
      subsequent CREB-mediated transcription in the nucleus accumbens shell, leading to
      behavioral depression. Surprisingly, this pathway seems not to be involved in
      behavioral depression caused by prolonged social isolation, suggesting distinct
      mechanisms underlying the two stressful contexts. In contrast, DeltaFosB-mediated
      gene expression in the nucleus accumbens shell confers resilience to stress.
      Repeated social defeat stress induces accumbal DeltaFosB expression in a stress
      resilient subset of individuals, whereas prolonged social isolation decreases
      this expression, leading to stress susceptibility. In addition to emotional
      changes, chronic stress also alters the mode of instrumental behavior from goal
      directed to habitual responding, with consistent morphological changes in
      striatal subregions responsible for the corresponding behavioral modes.
      Therefore, these clinical and preclinical findings suggest that striatal
      abnormalities play a role in emotional and cognitive changes associated with
      major depression.

PMID- 22868884
TI  - [The neuroscience of suicide].
AB  - Various postmortem brain studies have provided evidence that reduced serotonin (5
      HT) transmission in the ventrolateral prefrontal cortex (vlPFC) is associated
      with depression-related suicide. Suicide victims have fewer 5-HT transporter
      sites and a large number of postsynaptic 5-HT1A and 5-HT receptors in the vlPFC,
      which are implicated in behavioral inhibition and impulsivity. These could be
      compensatory changes in response to 5-HT hypofunction in depression and suicide.
      Selective serotonin reuptake inhibitors (SSRIs) are commonly used for the
      treatment of depression and suicidal ideation. 5-HT innervation of the PFC arises
      predominantly from 5-HT neurons in the brainstem dorsal raphe nucleus (DRN). In
      the DRN of suicide cases, 5-HT1A autoreceptors are increased and the levels of 5
      HT biosynthetic enzyme, tryptophan hydroxylase (TPH), are reduced. Reduced 5-HT1A
      feedback inhibition and increased TPH may reflect compensatory changes in
      response to 5-HT hypofunction in depression-related suicide. Genetic
      polymorphisms in TPH, 5-HT transporter (5-HTTLPR allele), and 5-HT2A receptor
      were examined for their association with depression-related suicide, but no
      consistent associations were found. Stress is a risk factor for depression and is
      linked to hyperactivity of the hypothalamo-pituitary-adrenal axis and suicide.
      Corticotropin-releasing factor (CRF)-immunoreactive varicose fibers were detected
      in the DRN of suicide victims, suggesting that CRF neurons in the paraventricular
      nucleus of the hypothalamus and 5-HT neurons in the DRN may form a circuit in
      stress-induced depression. Alcoholics are at a significantly greater risk of
      suicide than the general population. Alcoholism is associated with alterations in
      the 5-HT system.

PMID- 22868885
TI  - [Spinocerebellar ataxia type 36 (nicknamed Asidan)].
AB  - We report the phenotype of spinocerebellar ataxia type 36 (SCA36), which is a
      novel type of dominant cerebellar ataxia nicknamed as "Asidan," caused by the
      expansion of a hexanucleotide GGCCTG repeat in intron 1 of the nucleolar protein
      56 (NOP56) gene. Age at the onset of ataxia was 53.1 (3.4) years (mean[SD]).
      Truncal ataxia was the most frequent initial symptom (100%), followed by ataxic
      dysarthria (100%), limb ataxia (93%), and general hyperreflexia (79%). Tongue
      fasciculation and subsequent atrophy were observed in 71% of the cases,
      especially in those of a longer duration. Skeletal muscle fasciculation and
      atrophy in the limbs and trunk were also observed in 57% of the cases. To our
      knowledge, we describe for the first time a unique clinical feature of Asidan
      (SCA36)--relatively pure cerebellar ataxia with progressive motor neuron
      involvement during the course of disease-that puts SCA36 at the crossroad of SCA
      and amyotrophic lateral sclerosis.

PMID- 22868886
TI  - [An autopsied case of corticobasal degeneration with onset of nonfluent aphasia
      revealing symmetrical cerebral involvement].
AB  - Herein we describe a patient with established corticobasal degeneration with
      onset of nonfluent aphasia and showing symmetrical cerebral involvement. A 64
      year-old man with a speech disorder for 2 years visited our hospital. He had
      nonfluent aphasia (reduced spontaneous speech, loss of intonation, anomia,
      repetition disorder, and difficulty in speaking short sentences). He also showed
      right-sided motor neglect, hypertonus of the left lower limb, a mask-like facial
      expression, and difficulty in closing his eyes. He was restless and walked around
      even during examination, suggesting frontotemporal dementia (FTD). Single-photon
      emission computed tomography (SPECT) revealed symmetrical reduction of cerebral
      blood flow in the bilateral fronto-temporo-parietal lobes. His neurological
      condition deteriorated gradually and a year later he could not speak
      comprehensive sentences. Magnetic resonance imaging (MRI) of the head at age 70
      showed symmetrical atrophy of the bilateral fronto-temporal lobes. He died of
      respiratory failure after clinical problems lasting ten years. On pathological
      examination, the fixed brain weighed 1,010 g and showed bilateral symmetrical
      atrophy of the frontal lobes. Histopathological examination revealed neuronal
      loss and gliosis in the frontal lobes, especially in the frontal convexity,
      superior frontal gyrus and precentral gyrus. Gallyas-Braak silver staining showed
      astrocytic plaques, argyrophilic threads and coiled bodies mainly in the frontal
      lobes. The substantia nigra showed severe neuronal loss on both sides and
      presence of free melanin. Pathological diagnosis was corticobasal degeneration
      (CBD). We believe that the patient had nonfluent aphasia and FTD reflected in
      bilateral degeneration of the frontal lobes. Some cases of CBD may present with
      symmetrical degeneration of the brain, even though left-hemisphere symptoms such
      as aphasia reveal themselves at an early stage.

PMID- 22868887
TI  - [Neuromyelitis optica following thymectomy with severe spinal cord atrophy after
      frequent relapses for 30 years].
AB  - A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30
      years despite receiving steroid and azathioprine therapy. She developed MGFA
      Class IIIb type of myasthenia gravis (MG) at the age of 23, and thymectomy
      resulted in complete remission of MG. The initial symptoms of NMO, including
      headache, high fever, retrobulbar optic neuritis, and neurogenic bladder,
      appeared at the age of 30. Two years later, paraplegia also developed. Although
      she received oral administration of steroids or azathioprine and intravenous
      steroid pulse therapy for treatment of NMO for over 30 years, she experienced
      frequent relapses. The examination at the ages of 58 and 60 years showed that
      anti-aquaporin-4 antibody was absent. Intravenous immunoglobulin therapy
      administered in January and June 2009 was effective, and she had 2 years of
      remission of NMO attack. Spinal MRI after frequent NMO attacks for 30 years
      revealed an extended spinal cord atrophy involving the lower cervical region and
      the entire thoracic region. We describe and discuss the prognosis of NMO and the
      effectiveness of therapies in an NMO patient who underwent thymectomy for MG.

PMID- 22868888
TI  - [An autopsy case of 78-year-old female presenting with dementia during the course
      of amyotrophic lateral sclerosis].

PMID- 22868889
TI  - Low-cost high-speed imaging system for observing vocal fold vibration in voice
      disorders.
AB  - PURPOSE: The aim of this study was to establish a method to observe vocal fold
      vibration using a low-cost high-speed laryngeal imaging system. PROCEDURES: We
      assembled a high-speed imaging system with a consumer digital camera and a rigid
      laryngeal endoscope. The camera can shoot digital images at a rate of 1,200
      frames per second and be purchased for about USD 1,000 in Japan. RESULTS: We
      examined the normal and pathological vocal folds of 215 subjects with our new
      system and analyzed the vocal fold vibration in these subjects by playback of a
      video and kymograph images. CONCLUSIONS: Our high-speed laryngeal imaging system
      is highly cost-effective and can be a useful tool for examining the vocal folds
      of patients with voice disorders.

PMID- 22868890
TI  - The neuro-muscular system in continuously swimming cercariae from Belarus. I
      Xiphidiocercariae.
AB  - The neuromuscular system (NMS) in cercariae of Neoastiotrema trituri, Plagiorchis
      elegans, Omphalometra flexuosa, Skrjabinoeces similis and Prosthogonimus ovatus
      was studied with immunocytochemical methods and confocal scanning laser
      microscopy. The patterns of F-actin in the musculature, 5-HT immunoreactive (IR),
      FMRFamide-IR neuronal elements and alpha-tubulin-IR sensory receptors were
      investigated, and they were found to be rather similar in all the cercariae
      studied. Four species have seven paired 5-HT-IR neurons in the body, and P.
      elegans has eight. N. trituri has three 5-HT-IR neurons in each brain ganglion,
      while the other species have four. A high degree of conformity in the structure
      of the NMS was observed, probably reflecting the close phylogenetic relationship
      and the similar strategy of host finding.

PMID- 22868891
TI  - Trypanosoma cruzi: experimental parasitism in the central nervous system of
      albino mice.
AB  - Trypanosoma cruzi causes a pan-infection, Chagas disease, in American mammals
      through fecal transmission by triatomine insects, resulting in an acute phase
      parasitemia with intracellularity mainly in the myocells and cells of the central
      nervous system (CNS).The parasites, due to the immune response, then decrease in
      number, characteristic of the life-long chronicity of the disease. We infected a
      mouse model with isolates obtained from reservoirs and vectors from rural and
      urban endemic areas in Venezuela. Intracellular proliferation and differentiation
      of the parasite in astrocytes, microglia, neurons, endothelial cells of the
      piarachnoid, cells of the Purkinje layer, and spinal ganglion cells, as well as
      extracellularly in the neuropil, were evaluated during the acute phase. Damages
      were identified as meningoencephalitis, astrocytosis, reactive microglia, acute
      neuronal degeneration by central chromatolysis, endothelial cell hyperplasia,
      edema of the neuropil, and satellitosis. This is the first time that satellitosis
      has been reported from a mammal infected with T. cruzi. Intracellular T. cruzi
      and inflammatory infiltrates were found in cardiac and skeletal myocytes and
      liver cells. No parasitism or alterations to the CNS were observed in the chronic
      mice, although they did show myocarditis and myocitis with extensive infiltrates.
      Our results are discussed in relation to hypotheses that deny the importance of
      the presence of tissue parasites versus the direct relationship between these and
      the damages produced during the chronic phase of Chagas disease. We also review
      the mechanisms proposed as responsible for the nervous phase of this parasitosis.

PMID- 22868892
TI  - Enhanced haloarchaeal oil removal in hypersaline environments via organic
      nitrogen fertilization and illumination.
AB  - Hypersaline soil and pond water samples were mixed with 3 % crude oil, some
      samples were autoclaved to serve as sterile controls; experimental samples were
      not sterilized. After 6-week incubation at 40  degrees C under light/dark cycles,
      the soil microflora consumed 66 %, and after 4 weeks the pond water microflora
      consumed 63 % of the crude oil. Soil samples treated with 3 % casaminoacids lost
      89 % of their oil after 6 weeks and water samples lost 86 % after 4 weeks.
      Samples treated with casaminoacids and antibiotics that selectively inhibited
      bacteria, lost even more oil, up to 94 %. Soil-water mixtures incubated under
      continuous illumination lost double as much more oil than samples incubated in
      the dark. The soil-water mixture at time zero contained 1.3 * 10(4) CFU g(-1) of
      hydrocarbon-utilizing microorganisms which were affiliated to Halomonas
      aquamarina, Exiguobacterium aurantiacum, Haloferax sp., Salinococcus sp.,
      Marinococcus sp. and Halomonas sp. After 6-week incubation with oil, these
      numbers were 8.7 * 10(7) CFU g(-1) and the Haloferax sp. proportion in the total
      microflora increased from 20 to 93 %. Experiments using the individual cultures
      and three other haloarchaea isolated earlier from the same site confirmed that
      casaminoacids and light enhanced their oil consumption potential in batch
      cultures.

PMID- 22868893
TI  - Writing more specific exercise prescriptions.

PMID- 22868894
TI  - Wheelchair tennis match-play demands: effect of player rank and result.
AB  - PURPOSE: To examine the heart-rate (HR) response and court-movement variables
      during wheelchair tennis match play for high- (HIGH) and low- (LOW) performance
      ranked players. Analysis of physiological and movement-based responses during
      match play offers an insight into the demands of tennis, allowing practical
      recommendations to be made. METHODS: Fourteen male open-class players were
      monitored during tournament match play. A data logger was used to record distance
      and speed. HR was recorded during match play. RESULTS: Significant rank-by-result
      interactions revealed that HIGH winners covered more forward distance than HIGH
      losers (P < .05) and had higher average (P < .05) and minimum (P < .01) HRs than
      LOW winners. LOW losers had higher average (P < .01) and minimum (P < .001) HRs
      than LOW winners. Independent of result, a significant main effect for rank was
      identified for maximum (P < .001) and average (P < .001) speed and total (P <
      .001), reverse (P < .001), and forward-to-reverse (P < .001) distance, with
      higher values for HIGH. Independent of rank, losing players experienced higher
      minimum HRs (P < .05). Main effects for maximum HR and actual playing time were
      not significant. Average playing time was 52.0 (9.1) min. CONCLUSIONS: These data
      suggest that independent of rank, tennis players were active for sufficient time
      to confer health-enhancing effects. While the relative playing intensity is
      similar, HIGH players push faster and farther than LOW players. HIGH players are
      therefore more capable of responding to ball movement and the challenges of
      competitive match play. Adjustments to the sport may be required to encourage
      skill developmental in LOW players, who move at significantly lower speeds and
      cover less distance.

PMID- 22868895
TI  - Amplified spontaneous emission from single CdS nanoribbon with low symmetric
      cross sections.
AB  - CdS nanoribbons with various cross sections offer the opportunity to deeply
      understand the interaction between optical cavity and spontaneous emission.
      Herein, long tapered nanoribbons with the cross sections gradually changing were
      synthesized by a simple physical vapour deposition method. Morphology dependent
      micro-region photoluminescence (PL) spectroscopy is employed to show Purcell
      effect along different low symmetry cross sections. Spikes on the PL spectra
      reveal that local density of optical modes increases when the mode match happens
      between optical cavity and spontaneous emission. Bound exciton complex related
      amplified spontaneous emission is observed in a single CdS nanoribbon with well
      defined elliptical cross sections and optimized width/thickness ratio ~1.45.
      Polarized Raman and TEM confirmed that the nanoribbon with the elliptical cross
      section adopts the [0002] growth direction with good quality. The results suggest
      that the cross section resonant cavity would be of importance for both
      fundamental and practical application of cavity quantum electrodynamics in CdS
      nanoribbon.

PMID- 22868896
TI  - Neural correlates of weight gain with olanzapine.
AB  - CONTEXT Iatrogenic obesity caused by atypical antipsychotics increases the rate
      of death from all causes. Olanzapine is a commonly prescribed atypical
      antipsychotic medication that frequently causes weight gain. To our knowledge,
      the neural correlates of this weight gain have not been adequately studied in
      humans. OBJECTIVE To test the hypothesis that olanzapine treatment disrupts the
      neural activity associated with the anticipation and receipt (consumption) of
      food rewards (chocolate milk and tomato juice). DESIGN Event-related functional
      magnetic resonance imaging study, before and after a 1-week treatment with
      olanzapine. SETTING A university neuroimaging center. PARTICIPANTS Twenty-five
      healthy individuals. MAIN OUTCOME MEASURES Changes in blood oxygen level
      dependent activations to the anticipation and receipt of food rewards after
      olanzapine treatment. RESULTS One week of olanzapine treatment caused significant
      increases in weight, food consumption, and disinhibited eating. Our imaging data
      showed enhanced activations in the inferior frontal cortex, striatum, and
      anterior cingulate cortex to the anticipation of a food reward. Activation in the
      caudate and putamen were enhanced to the receipt of the rewarding food. We also
      found a decrease in reward responsivity to receipt of the rewarding food in the
      lateral orbital frontal cortex, an area of the brain thought to exercise
      inhibitory control on feeding. CONCLUSIONS Olanzapine treatment enhanced both the
      anticipatory and consummatory reward responses to food rewards in the brain
      reward circuitry that is known to respond to food rewards in healthy individuals.
      We also noted a decrease in responsivity to food consumption in a brain area
      thought to inhibit feeding behavior.

PMID- 22868897
TI  - Ambient air pollutants and acute case-fatality of cerebro-cardiovascular events:
      Takashima Stroke and AMI Registry, Japan (1988-2004).
AB  - BACKGROUND: Apart from the conventional risk factors, cerebro-cardiovascular
      disease (CVD) are also reported to be associated with air pollution, thus
      lowering the level of exposure might contribute in prevention activities to
      reduce the associated adverse outcomes. Though few studies conducted in Japan
      have reported on the CVD mortality but none have explored the effect of air
      pollutant exposure on the acute case-fatality of CVD. We investigated the effects
      of air pollution exposure on acute case-fatality of stroke and acute myocardial
      infarction (AMI) in a setting where pollutant levels are rather low. METHODS: We
      leveraged the data from the Takashima Stroke and AMI Registry, which covers a
      population of approximately 55,000 in Takashima County located in central Japan.
      The study period of 6,210 days (16 years, leap years also taken into account)
      were divided into quartiles of daily average pollutant concentration; suspended
      particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and
      photochemical oxidants (Ox). The stroke and AMI events were categorized to
      corresponding quartiles based on the pollution levels of the onset day. To study
      the effects of air pollutants, we estimated the fatality rate ratio across
      quartiles of the pollutants where the lowest quartile served as the reference.
      RESULTS: There were 307 (men: 153 and women: 154) fatal stroke cases within 28
      days of onset among the 2,038 first ever stroke during 1988-2004. In the same
      period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of
      onset among the 429 first ever AMI events. The mean of the measured pollutant
      levels were as follows: SPM 26.9 ug/m(3), SO(2) 3.9 ppb, NO(2) 16.0 ppb, and Ox
      28.4 ppb. Among the pollutants, higher levels of NO(2) showed increased fatality
      risk. In multi-pollutant model, the highest quartile of NO(2) was associated with
      60% higher stroke case-fatality risk in comparison to lowest quartile of NO(2).
      In the fully adjusted model the fatality-rate ratio was 1.65 (95% CI 1.06-2.57).
      This association was more prominent among stroke subtype of cerebral infarction.
      Other pollutant levels did not show any association with stroke or AMI case
      fatality. CONCLUSION: We observed association between NO(2) levels, an index of
      traffic related air pollution, with the acute case-fatality of stroke, especially
      cerebral infarction in our study population. Further studies are needed in
      different regions to determine the association between ambient air pollutants and
      acute cardiovascular fatalities.

PMID- 22868898
TI  - In vitro reproduction of endochondral ossification using a 3D mesenchymal stem
      cell construct.
AB  - Endochondral ossification is one of the essential bone development processes in
      vertebrates. Although researchers from a variety of fields, including
      cellular/molecular biology, chemistry, and materials science, have worked to gain
      a better understanding of the tissue development, integration of findings from
      these different fields remains a major challenge. An in vitro model system that
      reproduces endochondral ossification would be a valuable tool for overcoming this
      problem, because an in vitro standardized model system can be easily accessed by
      researchers from different fields. Here, we fabricated a large 3D mesenchymal
      stem cell (MSC) construct with a ball-like morphology, which is termed a cell
      ball, and cultured it under a hypoxia condition, since hypoxia causes
      chondrogenic differentiation of MSCs in primordial cartilage, which is crucial
      for endochondral ossification. Region-specific chondrogenic differentiation of
      MSCs and mineralization within the cartilage tissue were observed in the cell
      ball. The precipitated minerals were detected as hydroxyapatite. Consequently, a
      3D construct consisting of mineralized tissue surrounded by cartilage tissue was
      obtained. Moreover, the angiogenic activity of this synthesized tissue changed
      depending on the chondrogenic phenotype remains in the tissue, which is similar
      to what happens in the ossification process. Thus, this MSC cell ball system
      clearly reproduced the initial stage of endochondral ossification in vitro. This
      system is a promising tool for use as an in vitro model for investigating bone
      tissue development.

PMID- 22868899
TI  - The antitumor effect of the toll-like receptor 3 ligand polyinosinic-cytidylic
      acid as an adjuvant.
AB  - Although polyinosinic-polycytidylic acid (poly(I:C)) has been applied in tumor
      immunity as a Toll-like receptor 3 (TLR3) ligand, the interaction between
      poly(I:C) and TLR3 is still unclear, as are the mechanisms underlying the
      antitumor effect of poly(I:C). Our aim was to investigate the interaction between
      poly(I:C) and TLR3, as well as the mechanisms underlying the antitumor effect of
      poly(I:C). NK92 cells were maintained in medium (untreated group), or medium
      containing E7(44-62) (E7 group) or E7(44-62)+poly(I:C) (poly(I:C)/E7 group), and
      we measured the expression of TLR3 mRNA, p-p65, and IkappaB-alpha protein. The
      cells were first incubated in medium alone or medium containing TLR3 monoclonal
      antibody, and then in medium containing poly(I:C)/E7. Finally, we measured the
      level of interferon-beta (INF-beta) in the supernatant and determined the tumor
      cell-killing effect of the NK92 cells. At 1 h, the expression of TLR3 mRNA in the
      poly(I:C)/E7 group was markedly higher than that in the untreated and E7 groups
      (P < 0.05). When compared with the poly(I:C)/E7 group, the expression of IkappaB
      alpha was dramatically increased in the E7 and untreated groups, and the
      expression of p-p65 was dramatically decreased in the E7 and untreated groups
      (all P < 0.05). At 24 h, INF-beta content and tumor cell-killing activity in the
      poly(I:C)/E7 group were markedly higher than those in the untreated group (P <
      0.001, <0.05, respectively). Treatment with TLR3 monoclonal antibody
      significantly inhibited poly(I:C)/E7-induced INF-beta secretion and tumor cell
      killing activity in NK92 cells (P < 0.001, <0.05, respectively). The interaction
      between poly(I:C) and TLR3 plays an important role in the antitumor immunity of
      NK92 cells. In addition, the interaction between poly(I:C) and TLR3 increases INF
      beta expression, which may be attributed to the activation of NFkappaB.

PMID- 22868900
TI  - Daytime variations of tear osmolarity and tear meniscus volume.
AB  - OBJECTIVES: The aim of this study was to determine the pattern of variations in
      tear osmolarity and tear meniscus volume in patients with dry eyes and in healthy
      control subjects over an 8-hr daytime period. METHODS: Ten normal subjects (5 men
      and 5 women with a mean age of 27+/-7 years) and 10 dry eye patients (4 men and 6
      women with a mean age of 36+/-12 years) who had been diagnosed on the basis of
      having an ocular surface discomfort index >12 and a tear breakup time of <10 sec
      or Schirmer test score of <5 mm were included. The tear meniscus volumes of the
      participants were measured using ultrahigh resolution optical coherence
      tomography (OCT), and tear osmolarity was measured using the TearLab Osmolarity
      System. Both measurements protocols were conducted on the right eye of each
      participant every 2 hrs beginning at 8:30 AM and ending at 4:30 PM. The OCT
      imaging was performed first and was followed by osmolarity testing. RESULTS: The
      mean tear osmolarity of the dry eye patients was 304.0+/-10.8 mOsm/L, and the
      mean tear osmolarity of the normal subjects was 298.0+/-14.2 mOsm/L (P>0.05).
      Over the course of 8 hrs, the average measured osmolarities of the dry eye group
      varied by approximately 21.9+/-13.5 mOsm/L (range, 6-43 mOsm/L), and the average
      measured tear osmolarities of the normal group varied by approximately 21.0+/-9.2
      mOsm/L (range, 8-35 mOsm/L). At 2:30 PM, the average volume of the tear menisci
      in the dry eye group was significantly lower than that of the subjects in the
      normal group (P<0.05). No correlations between the tear meniscus volumes and tear
      osmolarities of either group were observed. CONCLUSIONS: Variations in the tear
      osmolarities of individual dry eye patients and healthy normal control subjects
      were documented over the course of 8 daytime hours. No relationships between tear
      osmolarities and tear meniscus volumes were observed.

PMID- 22868901
TI  - Effect of a warming device on contact lens case contamination.
AB  - PURPOSE: To examine the effectiveness of heating contact lens cases after
      disinfection on reducing microbial contamination. METHODS: One strain each of
      Pseudomonas aeruginosa (071) and Staphylococcus aureus (31) were used to set up
      robust biofilms in polypropylene contact lens cases. The effect of dilutions
      (from 1:10 to 1:1000) of trypticase soy broth (TSB) in phosphate-buffered saline
      and incubation time (24 to 48h) on the ability of strains to from biofilms with
      high levels of bacteria were first examined. Then the effect of increasing the
      temperature of incubation (from 14 degrees C to 60 degrees C) of biofilms during
      drying was examined. In the final set of experiments, biofilms of strains were
      subjected to heating in a warming device set to deliver 60 degrees C for 3 hours,
      and the effect of this temperature after disinfection with a multipurpose
      disinfecting solution (MPDS; containing polyquat and Aldox) was examined by
      culturing the number of viable bacterial cells remaining. RESULTS: A dilution of
      1:100 TSB for S. aureus 31 and 1:1000 TSB for P. aeruginosa 071 together with an
      incubation time of 24 hours gave high numbers of viable cells of these 2 strains
      adhered to the contact lens cases. Having established the biofilms of bacteria,
      heating these to 60 degrees C for 3 hours resulted in significant reductions in
      the number of viable cells that could be cultured (1 log reduction for S. aureus
      31, P=0.0003; 3.5 log reduction for P. aeruginosa 071, P=0.002). Exposing the
      biofilms of cells to a disinfection cycle (6h at ambient temperature) in the
      presence of the MPDS and air drying at ambient temperature resulted in 2441+/
      1237 colony-forming units/lens well for S. aureus 31 and 7401+/-4374 colony
      forming units/lens well for P. aeruginosa 071. Increasing the drying temperature
      to 60 degrees C resulted in zero viable cells (i.e., >=4log reduction) for either
      bacterial type. CONCLUSIONS: Using a warming device for contact lens cases after
      a disinfection cycle with an MPDS during drying for 3 hours results in
      substantial kill of biofilms of P. aeruginosa and S. aureus that have been formed
      in the wells of the cases.

PMID- 22868902
TI  - Not simply a matter of psoriatic arthritis: epidemiology of rheumatic diseases in
      psoriatic patients.
AB  - This study investigated the occurrence of rheumatic conditions (RCs) in a
      psoriasis (PSO)-dedicated dermatological clinic. PSO subjects with musculo
      skeletal discomfort, and/or carrying signs (articular/systemic, even
      asymptomatic) of RCs; and/or suffering flares of previously established psoriatic
      arthritis (PsA) were referred to rheumatologist for evaluation. Laboratory
      tests/imaging were performed as needed. Categorization adhered to RCs
      classification endorsed by the Italian Society of Rheumatology. Of the 1,200
      psoriatic subjects, 277 (23.1 %) were enrolled (146 females). The mean age was
      55.7 years (range 21-81), PSO duration was 13.5 years (range 0-62). Thirty-seven
      patients (13.4 %) were asymptomatic. On an average, 92 (7.6 %) patients/year were
      evaluated, of whom 79.4 % naive to rheumatological consultations (NRC).
      Osteoarthritis (OA) and PsA (isolated or combined) showed the highest prevalence,
      with 156 (56.3 %) and 110 cases (39.7 %), respectively. Among NRC subjects, the
      mean PsA annual incidence was 29.5 % (standard error of the mean +/-5.4 %). Other
      RCs, isolated or associated with PsA/OA, were diagnosed in 31 cases (11.2 %).
      Thirty-two subjects (11.5 %) had arthralgias, 20 of whom due to
      congenital/mechanical disorders, the remaining were unclassifiable. In
      conclusion, the largest part (88.5 %) of PSO subjects referred to rheumatologist
      showed some RCs. On annual basis, 29.5 % of naive enrolled patients were
      diagnosed as PsA.

PMID- 22868903
TI  - CYP2D6 update:  revised nomenclature for CYP2D7/2D6 hybrid genes.

PMID- 22868904
TI  - Does transgenic Cry1Ac + CpTI cotton pollen affect hypopharyngeal gland
      development and midgut proteolytic enzyme activity in the honey bee Apis
      mellifera L. (Hymenoptera, Apidae)?
AB  - The transgenic Cry1Ac (Bt toxin) + CpTI (Cowpea Trypsin Inhibitor) cotton
      cultivar CCRI41 is increasingly used in China and potential side effects on the
      honey bee Apis mellifera L. have been documented recently. Two studies have
      assessed potential lethal and sublethal effects in young bees fed with CCRI41
      cotton pollen but no effect was observed on learning capacities, although lower
      feeding activity in exposed honey bees was noted (antifeedant effect). The
      present study aimed at providing further insights into potential side effects of
      CCRI41 cotton on honey bees. Emerging honey bees were exposed to different pollen
      diets using no-choice feeding protocols (chronic exposure) in controlled
      laboratory conditions and we aimed at documenting potential mechanisms underneath
      the CCRI41 antifeedant effect previously reported. Activity of midgut proteolytic
      enzyme of young adult honey bees fed on CCRI41 cotton pollen were not
      significantly affected, i.e. previously observed antifeedant effect was not
      linked to disturbed activity of the proteolytic enzymes in bees' midgut.
      Hypopharyngeal gland development was assessed by quantifying total extractable
      proteins from the glands. Results suggested that CCRI41 cotton pollen carries no
      risk to hypopharyngeal gland development of young adult honey bees. In the two
      bioassays, honey bees exposed to 1 % soybean trypsin inhibitor were used as
      positive controls for both midgut proteolytic enzymes and hypopharyngeal gland
      proteins quantification, and bees exposed to 48 ppb (part per billion) (i.e. 48
      ng g(-1)) imidacloprid were used as controls for exposure to a sublethal
      concentration of toxic product. The results show that the previously reported
      antifeedant effect of CCRI41 cotton pollen on honey bees is not linked to effects
      on their midgut proteolytic enzymes or on the development of their hypopharyngeal
      glands. The results of the study are discussed in the framework of risk
      assessment of transgenic crops on honey bees.

PMID- 22868906
TI  - Temperature- and light-responsive smart polymer materials.
AB  - Stimuli-responsive polymers have been attracting great interest within the
      scientific community for several decades. The unique feature to respond to small
      changes in the environmental conditions has made this class of materials very
      promising for several applications in the field of nanoscience, nanotechnology
      and nanomedicine. So far, several different chemical, physical or biochemical
      stimuli have been investigated within natural or synthetic polymers. Very
      interesting and appealing seems to be the combination of several stimuli to tune
      the properties of these materials in manifold ways. Within this present review,
      we want to highlight the recent progress in the field of synthetic stimuli
      responsive polymers combining temperature and light responsiveness. 

PMID- 22868905
TI  - Inhibition of cellular efflux pumps involved in multi xenobiotic resistance (MXR)
      in echinoid larvae as a possible mode of action for increased ecotoxicological
      risk of mixtures.
AB  - In marine organisms the multi xenobiotic resistance (MXR) mechanism via e.g. P
      glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) is an
      important first line of defense against contaminants by pumping contaminants out
      of the cells. If compounds would impair the MXR mechanism, this could result in
      increased intracellular levels of other compounds, thereby potentiating their
      toxicity. A calcein-AM based larval cellular efflux pump inhibition assay (CEPIA)
      was developed for echinoid (Psammechinus miliaris) larvae and applied for several
      contaminants. The larval CEPIA revealed that triclosan (TCS) and the
      nanoparticles P-85((r)) (P-85) were 124 and 155* more potent inhibitors (IC(50)
      0.5 +/- 0.05 and 0.4 +/- 0.1 MUM, respectively) of efflux pumps than the model
      inhibitor Verapamil (VER). PFOS (heptadecafluorooctane sulfonic acid) and
      pentachlorophenol also were more potent than VER, 24 and 5*, respectively.
      Bisphenol A and o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT) inhibited efflux
      pumps with a potency 3* greater than VER. In a 48 h early life stage bioassay
      with P. miliaris, exposure to a non-lethal concentration of the inhibitors TCS,
      VER, the model MRP inhibitor MK-571, the nanoparticles P-85 and the model P-gp
      inhibitor PSC-833, increased the toxicity of the toxic model substrate for efflux
      pumps vinblastine by a factor of 2, 4, 4, 8 and 16, respectively. Our findings
      show that several contaminants accumulating in the marine environment inhibit
      cellular efflux pumps, which could potentiate toxic effects of efflux pumps
      substrates.

PMID- 22868907
TI  - Use of a single target blood pressure level in type 2 diabetes mellitus for all
      cardiovascular risk reduction: comment on "intensive and standard blood pressure
      targets in patients with type 2 diabetes mellitus".

PMID- 22868908
TI  - Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the
      eye.
AB  - Angiopoietin-like protein (Angptl) 2 is a key mediator linking obesity to chronic
      adipose-tissue inflammation and systemic insulin resistance, and increasing
      evidence has shown that Angptl2 is associated with various chronic inflammatory
      diseases such as cancer and dermatomyositis; however, it remains unclear that
      Angptl2 functions in acute inflammation. In this study, we investigate whether
      Angptl2 has a role in acute inflammation in the eye with endotoxin-induced
      uveitis (EIU). Angptl2 was widely expressed in the normal mouse retina, while
      Angptl2-/- mice did not exhibit any changes in retinal cell marker expression and
      morphological analyses. Treatment with lipopolysaccharide (LPS) stimulated
      retinal Angptl2 mRNA expression in vivo and in vitro. We generated EIU in wild
      type (C57BL/6) and Angptl2-/- mice by injecting LPS intraperitoneally. Compared
      with wild-type animals, Angptl2-/- mice significantly reduced various EIU
      associated cellular and molecular parameters including leukocyte adhesion to the
      retinal vessels and infiltration into the vitreous cavity and retinal mRNA
      expression levels of monocyte chemotactic protein-1, intercellular adhesion
      molecule-1, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha, together
      with nuclear translocation of nuclear factor (NF)-kappaB p65 subunit. In vitro,
      antibody-based inhibition of alpha5beta1 integrin, a receptor for Angptl2,
      significantly repressed LPS-induced expression of IL-6 and TNF-alpha, both of
      which are the major inflammatory cytokines derived from macrophages. The present
      findings indicate that Angptl2 mediates endotoxin-induced retinal inflammation
      through the activation of NF-kappaB signaling pathway and suggest a potential
      validity of Angptl2 as a new molecular target for the treatment of acute
      inflammation.

PMID- 22868909
TI  - Bradykinin inhibits hepatic gluconeogenesis in obese mice.
AB  - The kallikrein-kinin system (KKS) has been previously linked to glucose
      homeostasis. In isolated muscle or fat cells, acute bradykinin (BK) stimulation
      was shown to improve insulin action and increase glucose uptake by promoting
      glucose transporter 4 translocation to plasma membrane. However, the role for BK
      in the pathophysiology of obesity and type 2 diabetes remains largely unknown. To
      address this, we generated genetically obese mice (ob/ob) lacking the BK B2
      receptor (obB2KO). Despite similar body weight or fat accumulation, obB2KO mice
      showed increased fasting glycemia (162.3 +/- 28.2 mg/dl vs 85.3 +/- 13.3 mg/dl),
      hyperinsulinemia (7.71 +/- 1.75 ng/ml vs 4.09 +/- 0.51 ng/ml) and impaired
      glucose tolerance when compared with ob/ob control mice (obWT), indicating
      insulin resistance and impaired glucose homeostasis. This was corroborated by
      increased glucose production in response to a pyruvate challenge. Increased
      gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead
      box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor
      gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase
      (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). FoxO1 nuclear
      exclusion was also impaired, as the obB2KO mice showed increased levels of this
      transcription factor in the nucleus fraction of liver homogenates during random
      feeding. Intraportal injection of BK in lean mice was able to decrease the
      hepatic mRNA expression of FoxO1 and PEPCK. In conclusion, BK modulates glucose
      homeostasis by affecting hepatic glucose production in obWT. These results point
      to a protective role of the KKS in the pathophysiology of type 2 diabetes
      mellitus.

PMID- 22868910
TI  - Agro-ecological analysis for the EU water framework directive: an applied case
      study for the river contract of the Seveso basin (Italy).
AB  - The innovative approach to the protection and management of water resources at
      the basin scale introduced by the European Union water framework directive (WFD)
      requires new scientific tools. WFD implementation also requires the participation
      of many stakeholders (administrators, farmers and citizens) with the aim of
      improving the quality of river waters and basin ecosystems through cooperative
      planning. This approach encompasses different issues, such as agro-ecology, land
      use planning and water management. This paper presents the results of a
      methodology suggested for implementing the WFD in the case of the Seveso river
      contract in Italy, one of the recent WFD applications. The Seveso basin in the
      Lombardy region has been one of the most rapidly urbanizing areas in Italy over
      the last 50 years. First, land use changes in the last 50 years are assessed with
      the use of historical aerial photos. Then, elements of an ecological network
      along the river corridor are outlined, and different scenarios for enhancing
      existing ecological connections are assessed using indicators from graph theory.
      These scenarios were discussed in technical workshops with involved stakeholders
      of the river contract. The results show a damaged rural landscape, where
      urbanization processes have decimated the system of linear green features
      (hedges/rows). Progressive reconnections of some of the identified network nodes
      may significantly increase the connectivity and circuitry of the study area.

PMID- 22868911
TI  - Epiprofin/Sp6 regulates Wnt-BMP signaling and the establishment of cellular
      junctions during the bell stage of tooth development.
AB  - Epiprofin/Specificity Protein 6 (Epfn) is a Kruppel-like family (KLF)
      transcription factor that is critically involved in tooth morphogenesis and
      dental cell differentiation. However, its mechanism of action is still not fully
      understood. We have employed both loss-of-function and gain-of-function
      approaches to address the role of Epfn in the formation of cell junctions in
      dental cells and in the regulation of junction-associated signal transduction
      pathways. We have evaluated the expression of junction proteins in bell-stage
      incisor and molar tooth sections from Epfn(-/-) mice and in dental pulp MDPC-23
      cells overexpressing Epfn. In Epfn(-/-) mice, a dramatic reduction occurs in the
      expression of tight junction and adherens junction proteins and of the adherens
      junction-associated beta-catenin protein, a major effector of canonical Wnt
      signaling. Loss of cell junctions and beta-catenin in Epfn(-/-) mice is
      correlated with a clear decrease in bone morphogenetic protein 4 (BMP-4)
      expression, a decrease in nestin in the tooth mesenchyme, altered cell
      proliferation, and failure of ameloblast cell differentiation. Overexpression of
      Epfn in MDPC-23 cells results in an increased cellular accumulation of beta
      catenin protein, indicative of upregulation of canonical Wnt signaling. Together,
      these results suggest that Epfn enhances canonical Wnt/beta-catenin signaling in
      the developing dental pulp mesenchyme, a condition that promotes the activity of
      other downstream signaling pathways, such as BMP, which are fundamental for
      cellular induction and ameloblast differentiation. These altered signaling events
      might underlie some of the most prominent dental defects observed in Epfn(-/-)
      mice, such as the absence of ameloblasts and enamel, and might throw light on
      developmental malformations of the tooth, including hyperdontia.

PMID- 22868912
TI  - Tamoxifen-resistant, ER-positive MAC 51 cell line with a high metastatic
      potential developed from a spontaneous breast cancer mouse model.
AB  - We developed and characterized an estrogen-responsive and ER-positive murine
      breast cancer cell line (MAC51) from a spontaneous breast cancer animal model.
      These cells are overexpressed with K8, K18 and K19 proteins in an
      immunofluoresence assay. Upregulation of ER alpha was observed in the
      immunofluoresence assay, real-time PCR analysis and western blot assay. A
      colocalization experiment in MAC 51 showed cytoplasmic colocalization of K18 and
      K19 proteins with ER alpha. Real-time analysis of tumor samples from engrafted
      animals, MAC 51, metastatic liver and metastatic ovary revealed overexpression of
      K8 and K18 compared to the respective controls. A hormone responsive experiment
      in immunodeficient mice showed highly significant decreases in estrogen and tumor
      volume after 14 days ovariectomization. The tumorogenicity assay showed higher (3
      * 10 (5)) and lower (3 * 10(4)) concentrations of MAC 51 cells that developed
      tumors within 2 weeks post-transplantation. Tumor morphology and histology
      resembled a sarcoma pattern but our spontaneous model appeared in an
      adenocarcinoma pattern. Metastasis to different organs occurred through
      hematogenous and lymphatic routes. We assessed the potency of the anticancer
      effect in MAC 51 cells by treating various anticancer drugs with E2, followed by
      studying apoptotic gene expression profiles. E2 and E2+ tamoxifen-treated cells
      showed upregulation of apoptotic genes caspase 1, 3, 9, P53 and Bcl-xl but the
      tamoxifen- and paclitaxel-treated cells did not upregulate the apoptotic genes.
      Tamoxifen-resistant, ER-positive and high metastatic potential cell lines from
      murine origin are very rare. Also, estrogen greatly induced apoptosis in this
      cell line, hence MAC 51 has a greater application potential to evaluate low doses
      of estrogen with other targeted therapeutic drugs to treat breast cancer.

PMID- 22868913
TI  - Fluorescent transgenic mice suitable for multi-color aggregation chimera studies.
AB  - We recently reported a novel method of mouse transgenesis called Pronuclear
      Injection-based Targeted Transgenisis (PITT) using which a series of fluorescent
      transgenic (Tg) mice lines were generated. These lines, unlike those generated
      using conventional random integration methods, express the transgenes faithfully
      and reproducibly generation after generation. Because of this superior nature,
      these lines are ideal for the generation of multi-colored aggregation chimeras
      that can be used to study cell-cell interactions and lineage analyses in living
      embryos/organs, where the transgenes can be detected and the clonal origin of a
      given cell population easily traced by its distinct fluorescence. In this study,
      to verify if Tg fluorescent mice generated through PITT were suitable for such
      applications, we sought to generate chimeric blastocysts and chimeric-Tg mice by
      aggregating two- or three-colored 8-cell embryos. Our analyses using these models
      led to the following observations. First, we noticed that cell mixing was
      infrequent during the stages of morula to early blastocyst. Second, chimeric
      fetuses obtained after aggregation of the two-colored 8-cell embryos exhibited
      uniform cell mixing. And third, in the organs of adult chimeric mice, the mode of
      cell distribution could be either clonal or polyclonal, as previously pointed out
      by others. Implications of our novel and improved Tg-chimeric mice approach for
      clonal cell lineage and developmental studies are discussed.

PMID- 22868915
TI  - Regenerating cardiac cells: insights from the bench and the clinic.
AB  - A major challenge in cardiovascular regenerative medicine is the development of
      novel therapeutic strategies to restore the function of cardiac muscle in the
      failing heart. The heart has historically been regarded as a terminally
      differentiated organ that does not have the potential to regenerate. This concept
      has been updated by the discovery of cardiac stem and progenitor cells that
      reside in the adult mammalian heart. Whereas diverse types of adult cardiac stem
      or progenitor cells have been described, we still do not know whether these cells
      share a common origin. A better understanding of the physiology of cardiac stem
      and progenitor cells should advance the successful use of regenerative medicine
      as a viable therapy for heart disease. In this review, we summarize current
      knowledge of the various adult cardiac stem and progenitor cell types that have
      been discovered. We also review clinical trials presently being undertaken with
      adult stem cells to repair the injured myocardium in patients with coronary
      artery disease.

PMID- 22868916
TI  - American Society of Breast Surgeons presidential address: could quality measures
      impede quality care?
AB  - Transparency and accountability are becoming more important, and publically
      reported quality measures will be used increasingly to determine how surgeons are
      viewed and reimbursed. That is a good thing if it is done correctly, but poorly
      designed quality measures might actually interfere with patient care. It will be
      necessary for ASBrS to remain involved in the development of relevant, true data
      based measures of quality that have appropriate benchmarks and no unintended
      consequences. Importantly, the quality measures need to include all reasonable
      treatment options so that quality care is enhanced and not impeded.

PMID- 22868914
TI  - Translocator protein (Tspo) gene promoter-driven green fluorescent protein
      synthesis in transgenic mice: an in vivo model to study Tspo transcription.
AB  - Translocator protein (TSPO), previously known as the peripheral-type
      benzodiazepine receptor, is a ubiquitous drug- and cholesterol-binding protein
      primarily found in the outer mitochondrial membrane as part of a mitochondrial
      cholesterol transport complex. TSPO is present at higher levels in steroid
      synthesizing and rapidly proliferating tissues and its biological role has been
      mainly linked to mitochondrial function, steroidogenesis and cell
      proliferation/apoptosis. Aberrant TSPO levels have been linked to multiple
      diseases, including cancer, endocrine disorders, brain injury, neurodegeneration,
      ischemia-reperfusion injury and inflammatory diseases. Investigation of the
      functions of this protein in vitro and in vivo have been mainly carried out using
      high-affinity drug ligands, such as isoquinoline carboxamides and benzodiazepines
      and more recently, gene silencing methods. To establish a model to study the
      regulation of Tspo transcription in vivo, we generated a transgenic mouse model
      expressing green fluorescent protein (GFP) from Aequorea coerulescens under
      control of the Tspo promoter region (Tspo-AcGFP). The expression profiles of Tspo
      AcGFP, endogenous TSPO and Tspo mRNA were found to be well-correlated. Tspo-AcGFP
      synthesis in the transgenic mice was seen in almost every tissue examined and as
      with TSPO in wild-type mice, Tspo-AcGFP was highly expressed in steroidogenic
      cells of the endocrine and reproductive systems, epithelial cells of the
      digestive system, skeletal muscle and other organs. In summary, this transgenic
      Tspo-AcGFP mouse model recapitulates endogenous Tspo expression patterns and
      could be a useful, tractable tool for monitoring the transcriptional regulation
      and function of Tspo in live animal experiments.

PMID- 22868917
TI  - MicroRNA-200a and -200b mediated hepatocellular carcinoma cell migration through
      the epithelial to mesenchymal transition markers.
AB  - BACKGROUND: MicroRNAs (miRNAs) play an essential role in mediating gene
      expression in both normal and malignant cells. However, little is known about
      specific miRNAs during the development of hepatocellular carcinoma (HCC) from
      well-differentiated to poorly differentiated cells. METHODS: We performed miRNA
      array analysis of three different HCC cell lines: HepG2, HepJ5, and skHep-1. The
      expression patterns of miR-200 family members were confirmed by real-time
      polymerase chain reaction (PCR). We overexpressed miR-200 family members by using
      a lentivirus system and selected for stably transduced cells using antibiotics.
      The migration ability of the cells was tested using the Transwell migration assay
      system. RESULTS: Our miRNA array and real-time PCR results indicated a decrease
      in the expression of miR-200 family members in poorly differentiated skHep-1
      cells compared with well-differentiated HepG2 cells. We overexpressed miR-200a
      and miR-200b in both HepJ5 and skHep-1 cells and found that the overexpression of
      the miR-200 family members did not influence proliferation, although migration
      was decreased in these cells. We found that overexpression of miR-200 family
      members led to an upregulation of E-cadherin expression in both HepJ5 and skHep-1
      cells. Furthermore, we silenced E-cadherin expression by shRNA in miR200a-HepJ5
      cells and found that the migratory ability of these cells was enhanced upon the
      decrease in E-cadherin expression. CONCLUSIONS: Members of the miR-200 family
      (miR-200a and miR-200b) play important roles in HCC migration by regulating E
      cadherin expression.

PMID- 22868918
TI  - The challenge of defining guidelines for sentinel lymph node biopsy in patients
      with thin primary cutaneous melanomas.

PMID- 22868919
TI  - Quality of life in patients after cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy: is it worth the risk?
AB  - OBJECTIVE: To investigate the course of health-related quality of life (HQL) over
      time in patients with peritoneal carcinomatosis (PC) after complete cytoreductive
      surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS:
      Prospective, single-center, nonrandomized cohort study using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire.
      RESULTS: Ninety patients who underwent CRS and HIPEC for PC in our institution
      were enrolled in the study. Mean age was 56 years (range 27-77 years) (61%
      female). Primary tumor was colorectal in 21%, ovarian in 19%, pseudomyxoma
      peritonei in 16%, an appendix tumor in 16%, gastric cancer in 10%, and peritoneal
      mesothelioma in 13% of cases. Mean peritoneal carcinomatosis index was 22 (range
      2-39). Mean global health status score was 69+/-25 preoperatively and 55+/-20,
      66+/-22, 66+/-23, 71+/-23, and 78+/-21 at months 1, 6, 12, 24, and 36,
      respectively. Physical and role function recovered significantly at 6 months and
      were close to baseline at the 24-month measurement. Emotional function starting
      from a low baseline recovered to baseline by month 12. Cognitive and social
      function had slow recovery on follow-up. Fatigue, diarrhea, dyspnea, and sleep
      disturbance were symptoms persistent at 6-month follow-up, improving later on in
      survivors. CONCLUSIONS: Survivors after CRS and HIPEC have postoperative quality
      of life similar to preoperatively, with most of the reduced elements recovering
      after 6-12 months. We conclude that reduced quality of life of patients after CRS
      and HIPEC should not be used as an argument to deny surgical therapy to these
      patients.

PMID- 22868920
TI  - Sestamibi imaging for primary hyperparathyroidism: the impact of surgeon
      interpretation and radiologist volume.
AB  - BACKGROUND: Preoperative localization is the first step towards minimally
      invasive targeted parathyroidectomy. While there are data emphasizing that
      surgeon experience optimizes operative outcomes, the role of the radiologist's
      experience in successful preoperative imaging is unclear. We hypothesized that
      the accuracy of sestamibi scanning for primary hyperparathyroidism is dependent
      upon surgeon interpretation and radiologist volume. METHODS: Between January 2000
      to August 2009, 1,255 patients underwent parathyroidectomy for
      hyperparathyroidism at our institution. Of these, 763 had sestamibi scans for
      primary hyperparathyroidism. All scans were reviewed by surgeons and radiologists
      blinded, and were correlated with the operative findings and pathological
      reports. Radiologists were grouped into high volume (>50 cases/year, HV-RAD) or
      low volume (<50 cases/year, LV-RAD) based upon a database of >6,000 parathyroid
      cases reported by 89 regional hospitals. RESULTS: Of the 763 patients, 77 % were
      female and the mean age was 60 years. Mean baseline calcium and parathyroid
      hormone levels were 11.2 +/- 0.03 mg/dl and 133 +/- 3.27 pg/ml, respectively. The
      sensitivity of the surgeon (93 %) was higher than both HV (83 %) and LV (72 %)
      radiologists. Importantly, the positive predictive values were similar: 96 % for
      surgeon, 93 % for HV-RAD, and 98 % for LV-RAD. As a result, out of 99 scans which
      were correctly read by the surgeon but not by radiologist, 84 were read as
      negative by radiologist, 11 on the wrong side of the neck, and 4 on the same side
      but the wrong gland. CONCLUSIONS: Surgeon interpretation and radiologist volume
      increase the likelihood of successful preoperative sestamibi parathyroid
      localization for primary hyperparathyroidism. We recommend that imaging be
      reviewed by experienced parathyroid surgeons rather than relying on radiological
      interpretation alone.

PMID- 22868921
TI  - Hepatic pedicle clamping during hepatic resection for colorectal liver
      metastases: no impact on survival or hepatic recurrence.
AB  - BACKGROUND: Hepatic pedicle clamping is often used during liver resection. While
      its use reduces blood loss and transfusion requirements, the long-term effect on
      survival and recurrence has been debated. This study evaluates the effect of
      hepatic pedicle clamping [i.e., Pringle maneuver (PM)] on survival and recurrence
      following hepatic resection for colorectal liver metastasis (CRLM). METHODS:
      Patients who underwent R0 resection for CRLM from 1991 to 2004 were identified
      from a prospectively maintained database. Operative, perioperative, and
      clinicopathological variables were analyzed. The primary outcomes were disease
      free survival (DFS) and liver recurrence (LR). Disease extent was categorized
      using a well-defined clinical risk score (CRS). Subgroup analysis was performed
      for patients given preoperative systemic chemotherapy and postoperative pump
      chemotherapy. RESULTS: This study included 928 consecutive patients with median
      follow-up of 8.9 years. PM was utilized in 874 (94%) patients, with median time
      of 35 min (range 1-181 min). On univariate analysis, only resection type
      (p<0.001) and tumor number (p=0.002) were associated with use of PM. Younger age
      (p=0.006), longer operative time (p<0.001), and multiple tumors (p=0.006) were
      associated with prolonged PM (>60 min). There was no association between DFS,
      overall survival (OS) or LR and Pringle time. Neither the CRS nor use of
      neoadjuvant therapy stratified disease-related outcome with respect to use of PM.
      CONCLUSIONS: PM was used in most patients undergoing resection for CRLM and did
      not adversely influence intrahepatic recurrence, DFS, or OS.

PMID- 22868922
TI  - Proceed with caution: vascular resection at pancreaticoduodenectomy.

PMID- 22868923
TI  - Epstein-Barr virus infection and altered control of apoptotic pathways in
      posttransplant lymphoproliferative disorders.
AB  - Posttransplant lymphoproliferative disorders (PTLD) represent a spectrum of
      lymphoid diseases complicating the clinical course of transplant recipients. Most
      PTLD are Epstein-Barr virus (EBV) associated with viral latency type III. Several
      in vitro studies have revealed an interaction between EBV latency proteins and
      molecules of the apoptosis pathway. Data on human PTLD regarding an association
      between Bcl-2 family proteins and EBV are scarce. We analyzed 60 primary PTLD for
      expression of 8 anti- (Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic proteins (Bak
      and Bax), the so-called BH3-only proteins (Bad, Bid, Bim, and Puma), as well as
      the apoptosis effector cleaved PARP by immunohistochemistry. Bim and cleaved PARP
      were both significantly (p = 0.001 and p = 5.251e-6) downregulated in EBV
      positive compared to EBV-negative PTLD [Bim: 6/40 (15%), cleaved PARP: 10/43
      (23%), vs. Bim: 13/16 (81%), cleaved PARP: 12/17 (71%)]. Additionally, we
      observed a tendency toward increased Bcl-2 protein expression (p = 0.24) in EBV
      positive PTLD. Hence, we provide evidence of a distinct regulation of Bcl-2
      family proteins in EBV-positive versus negative PTLD. The low-expression pattern
      of the proapoptotic proteins Bim and cleaved PARP together with the high
      expression pattern of the antiapoptotic protein Bcl-2 by trend in EBV-positive
      tumor cells suggests disruption of the apoptotic pathway by EBV in PTLD,
      promoting survival signals in the host cells.

PMID- 22868924
TI  - Vasculitis syndromes: AAV encompasses two major genetically distinct conditions
      with different autoantibody specificities.

PMID- 22868926
TI  - Osteoarthritis: subchondral bone erosion in hand OA: insights into the role of
      inflammation.

PMID- 22868925
TI  - Bone remodelling in osteoarthritis.
AB  - The classical view of the pathogenesis of osteoarthritis (OA) is that subchondral
      sclerosis is associated with, and perhaps causes, age-related joint degeneration.
      Recent observations have demonstrated that OA is associated with early loss of
      bone owing to increased bone remodelling, followed by slow turnover leading to
      densification of the subchondral plate and complete loss of cartilage.
      Subchondral densification is a late event in OA that involves only the
      subchondral plate and calcified cartilage; the subchondral cancellous bone
      beneath the subchondral plate may remain osteopenic. In experimental models,
      inducing subchondral sclerosis without allowing the prior stage of increased bone
      remodelling to occur does not lead to progressive OA. Therefore, both early-stage
      increased remodelling and bone loss, and the late-stage slow remodelling and
      subchondral densification are important components of the pathogenetic process
      that leads to OA. The apparent paradoxical observations that OA is associated
      with both increased remodelling and osteopenia, as well as decreased remodelling
      and sclerosis, are consistent with the spatial and temporal separation of these
      processes during joint degeneration. This Review provides an overview of current
      knowledge on OA and discusses the role of subchondral bone in the initiation and
      progression of OA. A hypothetical model of OA pathogenesis is proposed.

PMID- 22868928
TI  - Connective tissue diseases: classification criteria for SLE: the latest-but not
      least-attempt.

PMID- 22868927
TI  - Platelets: active players in the pathogenesis of arthritis and SLE.
AB  - Nearly one trillion platelets circulate in the blood to monitor and preserve the
      integrity of the vasculature. However, haemostasis is not their only function.
      Platelets are also potent immune cells capable of a range of effector responses.
      Studies have shown that platelets can have unexpected roles in rheumatic
      diseases. In patients with rheumatoid arthritis (RA), IL-1-containing platelet
      derived vesicles called microparticles are abundant in arthritic joint fluid.
      These microparticles can elicit production of inflammatory mediators from
      resident synovial fibroblasts, which have an integral role in the development of
      arthritis. Platelets also serve as a source of prostaglandins that contribute to
      synovial inflammation. Furthermore, serotonin released by platelets helps drive
      the persistent vascular permeability that characterizes the microvasculature of
      the inflamed synovium, an unexpected function for a cell that more typically
      serves as a guardian of vascular integrity. Beyond RA, platelet activation has
      been observed in systemic lupus erythematosus, mediated at least in part through
      the interaction of circulating immune complexes with platelet Fc receptors and by
      promotion of interferon release from plasmacytoid dendritic cells. These findings
      point to a distinct role for platelets in autoimmunity and support the
      possibility that platelets are an attractive target in rheumatic disease.

PMID- 22868929
TI  - Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits
      proliferation of human pancreatic cancer PANC-1 cells.
AB  - Oncogenic KRAS, an important target for antitumor therapy, contributes to
      pancreatic cancer tumorigenesis, progression and maintenance. However,
      intracellular compensation regulation can help cells to resist the targeted
      therapy. Gene knockdown method such as RNAi may help to understand this
      intracellular regulatory system and discover novel therapeutic approach. In this
      study, two stable transfected cell lines were constructed through lentivirus
      mediated shRNA targeting KRAS of PANC-1 cells, to investigate cell response to
      the knockdown of KRAS. Human whole genome microarray was then used to compare the
      gene expression profile. As a result, ribosomal proteins L26 and L29 (RPL26 and
      RPL29) were dramatically upregulated by KRAS-shRNA specifically. To identify
      whether RPL26 or RPL29 was critical for PANC-1 cells, siRNAs against RPL26 and
      RPL29 were designed and transfected in vitro. The results showed that knockdown
      of RPL26 or RPL29 expression significantly suppressed cell proliferation, induced
      cell arrest at G0/G1 phase and enhanced cell apoptosis. Reactive oxygen species
      (ROS) assay indicated that silencing of RPL26 or RPL29 markedly decreased the
      intracellular ROS generation. Our findings imply that siRNA interference against
      RPL26 and RPL29 is of potential value for intervention of pancreatic cancer.

PMID- 22868932
TI  - William Blake's The Great Red Dragon and the Woman Clothed With the Sun.

PMID- 22868933
TI  - Randomized trial of behavior therapy for adults with Tourette syndrome.
AB  - CONTEXT: Tics in Tourette syndrome begin in childhood, peak in early adolescence,
      and often decrease by early adulthood. However, some adult patients continue to
      have impairing tics. Medications for tics are often effective but can cause
      adverse effects. Behavior therapy may offer an alternative but has not been
      examined in a large-scale controlled trial in adults. OBJECTIVE: To test the
      efficacy of a comprehensive behavioral intervention for tics in adults with
      Tourette syndrome of at least moderate severity. DESIGN: A randomized controlled
      trial with posttreatment evaluations at 3 and 6 months for positive responders.
      SETTING: Three outpatient research clinics. PATIENTS: Patients (N = 122; 78
      males; age range, 16-69 years) with Tourette syndrome or chronic tic disorder
      were recruited between December 27, 2005, and May 21, 2009. INTERVENTIONS:
      Patients received 8 sessions of comprehensive behavioral intervention for tics or
      8 sessions of supportive treatment for 10 weeks. Patients with a positive
      response were given 3 monthly booster sessions. MAIN OUTCOME MEASURES: Total tic
      score on the Yale Global Tic Severity Scale and the Clinical Global Impression
      Improvement scale rated by a clinician masked to treatment assignment. RESULTS:
      Behavior therapy was associated with a significantly greater mean (SD) decrease
      on the Yale Global Tic Severity Scale (24.0 [6.47] to 17.8 [7.32]) from baseline
      to end point compared with the control treatment (21.8 [6.59] to 19.3 [7.40]) (P
      < .001; effect size = 0.57). Twenty-four of 63 patients (38.1%) were rated as
      much improved or very much improved on the Clinical Global Impression-Improvement
      scale compared with 4 of 63 (6.4%) in the control group (P < .001). Attrition was
      13.9%, with no difference across groups. Patients receiving behavior therapy who
      were available for assessment at 6 months after treatment showed continued
      benefit. CONCLUSION: Comprehensive behavior therapy is a safe and effective
      intervention for adults with Tourette syndrome. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00231985.

PMID- 22868934
TI  - Interactive effect of apolipoprotein e genotype and age on hippocampal activation
      during memory processing in healthy adults.
AB  - CONTEXT: Although the apolipoprotein E (APOE) epsilon4 allele is a major genetic
      risk factor for late-onset Alzheimer disease, its effect on hippocampal function
      during episodic memory is controversial because studies have yielded mixed
      results. The age of the studied cohorts may contribute to this apparent
      inconsistency: activation for epsilon4 carriers tends to be increased in studies
      of older adults but decreased in some studies of younger adults. Consistent with
      differential age effects, research in transgenic mice suggests that the epsilon4
      allele may particularly affect the aging process. OBJECTIVE: To define the
      interactions of age and this allelic variation on brain activation during
      episodic memory across adult life in healthy individuals. DESIGN: Functional
      magnetic resonance imaging (fMRI) using an episodic memory paradigm to test for
      differences in neuroactivation across APOE genotypes and age groups. SETTING: A
      federal research institute. PARTICIPANTS: Healthy white volunteers (APOE epsilon3
      homozygotes and epsilon2 and epsilon4 heterozygotes) completed the fMRI task (133
      volunteers aged 19-77 years). MAIN OUTCOME MEASURE: Memory-related regional blood
      oxygenation level-dependent (BOLD) activation. RESULTS: Genotype affected the
      pattern of change in hippocampal BOLD activation across the adult lifespan: older
      age was associated with decreased activation in epsilon2 carriers and, to a
      lesser extent, in epsilon3 homozygotes, but this pattern was not observed in
      epsilon4 carriers. Among young participants, epsilon4 carriers had less
      hippocampal activation compared with epsilon3 homozygotes despite similar task
      performance. CONCLUSIONS: The findings support the hypothesis that aging and APOE
      allele status have interacting effects on the neural substrate of episodic memory
      and lend clarification to disparities in the literature. The stepwise decrease in
      activation with age found among genotype groups resembles the order of
      susceptibility to Alzheimer disease, suggesting a compensatory neurobiological
      mechanism in older asymptomatic epsilon4 carriers.

PMID- 22868935
TI  - Neural responses to affective and cognitive theory of mind in children with
      conduct problems and varying levels of callous-unemotional traits.
AB  - CONTEXT: Reduced neural responses to others' distress is hypothesized to play a
      critical role in conduct problems coupled with callous-unemotional traits,
      whereas increased neural responses to affective stimuli may accompany conduct
      problems without callous-unemotional traits. Heterogeneity of affective profiles
      in conduct problems may account for inconsistent neuroimaging findings in this
      population. OBJECTIVES: To broaden understanding of neural processing in conduct
      problems using an affective processing task including an empathy component as
      well as to explore dimensional contributions of conduct problems symptoms and
      callous-unemotional traits to variance in affective neural responses. DESIGN:
      Case-control study. SETTING: On-campus neuroimaging facility. PARTICIPANTS:
      Thirty-one boys with conduct problems (mean age, 14.34 years) and 16 typically
      developing control subjects (mean age, 13.51 years) matched for age (range, 10-16
      years), IQ, socioeconomic status, handedness, and race/ethnicity. Participants
      were recruited using screening questionnaires in a community-based volunteer
      sample. MAIN OUTCOME MEASURES: Functional magnetic resonance imaging of a task
      contrasting affective and cognitive theory of mind judgments. RESULTS: Relative
      to typically developing children, children with conduct problems showed reduced
      activation in right amygdala and anterior insula for affective vs cognitive
      theory of mind judgments. Furthermore, in the right amygdala, regression analysis
      within the conduct-problems group showed suppressor effects between ratings of
      conduct problems and callous-unemotional traits. Specifically, unique variance
      associated with conduct problems was positively correlated with amygdala
      reactivity, whereas unique variance associated with callous-unemotional traits
      was negatively correlated with amygdala reactivity. These associations were not
      explained by hyperactivity, depression/anxiety symptoms, or alcohol use ratings.
      CONCLUSIONS: Childhood conduct problems are associated with amygdala and anterior
      insula hypoactivity during a complex affective processing task including an
      empathy component. Suppressor effects between conduct problems and callous
      unemotional traits in the amygdala suggest a potential neural substrate for
      heterogeneity in affective profiles associated with conduct problems.

PMID- 22868936
TI  - Association of mental disorders in early adulthood and later psychiatric hospital
      admissions and mortality in a cohort study of more than 1 million men.
AB  - CONTEXT: Mental disorders have been associated with increased mortality, but the
      evidence is primarily based on hospital admissions for psychoses. The underlying
      mechanisms are unclear. OBJECTIVES: To investigate whether the risks of death
      associated with mental disorders diagnosed in young men are similar to those
      associated with admission for these disorders and to examine the role of
      confounding or mediating factors. DESIGN: Prospective cohort study in which
      mental disorders were assessed by psychiatric interview during a medical
      examination on conscription for military service at a mean age of 18.3 years and
      data on psychiatric hospital admissions and mortality during a mean 22.6 years of
      follow-up were obtained from national registers. SETTING: Sweden. PARTICIPANTS: A
      total of 1,095,338 men conscripted between 1969 and 1994. MAIN OUTCOME MEASURE:
      All-cause mortality according to diagnoses of schizophrenia, other nonaffective
      psychoses, bipolar or depressive disorders, neurotic and adjustment disorders,
      personality disorders, and alcohol-related or other substance use disorders at
      conscription and on hospital admission. RESULTS: Diagnosis of mental disorder at
      conscription or on hospital admission was associated with increased mortality.
      Age-adjusted hazard ratios according to diagnoses at conscription ranged from
      1.81 (95% CI, 1.54-2.10) (depressive disorders) to 5.55 (95% CI, 1.79-17.2)
      (bipolar disorders). The equivalent figures according to hospital diagnoses
      ranged from 5.46 (95% CI, 5.06-5.89) (neurotic and adjustment disorders) to 11.2
      (95% CI, 10.4-12.0) (other substance use disorders) in men born from 1951 to 1958
      and increased in men born later. Adjustment for early-life socioeconomic status,
      body mass index, and blood pressure had little effect on these associations, but
      they were partially attenuated by adjustment for smoking, alcohol intake,
      intelligence, educational level, and late-life socioeconomic status. These
      associations were not primarily due to deaths from suicide. CONCLUSION: The
      increased risk of premature death associated with mental disorder is not confined
      to those whose illness is severe enough for hospitalization or those with
      psychotic or substance use disorders.

PMID- 22868938
TI  - Effect of brain structure, brain function, and brain connectivity on relapse in
      alcohol-dependent patients.
AB  - CONTEXT: In alcohol-dependent patients, brain atrophy and functional brain
      activation elicited by alcohol-associated stimuli may predict relapse. However,
      to date, the interaction between both factors has not been studied. OBJECTIVE: To
      determine whether results from structural and functional magnetic resonance
      imaging are associated with relapse in detoxified alcohol-dependent patients.
      DESIGN: A cue-reactivity functional magnetic resonance experiment with alcohol
      associated and neutral stimuli. After a follow-up period of 3 months, the group
      of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and
      30 relapsers. SETTING: Faculty for Clinical Medicine Mannheim at the University
      of Heidelberg, Germany. PARTICIPANTS: A total of 46 detoxified alcohol-dependent
      patients and 46 age- and sex-matched healthy control subjects MAIN OUTCOME
      MEASURES: Local gray matter volume, local stimulus-related functional magnetic
      resonance imaging activation, joint analyses of structural and functional data
      with Biological Parametric Mapping, and connectivity analyses adopting the
      psychophysiological interaction approach. RESULTS: Subsequent relapsers showed
      pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial
      prefrontal and anterior cingulate cortex, compared with healthy controls and
      patients who remained abstinent. The local gray matter volume-corrected brain
      response elicited by alcohol-associated vs neutral stimuli in the left medial
      prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers
      displayed an increased neural response in the midbrain (the ventral tegmental
      area extending into the subthalamic nucleus) and ventral striatum. For alcohol
      associated vs neutral stimuli in abstainers compared with relapsers, the analyses
      of the psychophysiological interaction showed a stronger functional connectivity
      between the midbrain and the left amygdala and between the midbrain and the left
      orbitofrontal cortex. CONCLUSIONS: Subsequent relapsers displayed increased brain
      atrophy in brain areas associated with error monitoring and behavioral control.
      Correcting for gray matter reductions, we found that, in these patients, alcohol
      related cues elicited increased activation in brain areas associated with
      attentional bias toward these cues and that, in patients who remained abstinent,
      increased activation and connectivity were observed in brain areas associated
      with processing of salient or aversive stimuli.

PMID- 22868937
TI  - Neural mechanisms of decision making in hoarding disorder.
AB  - CONTEXT: Hoarding disorder (HD), previously considered a subtype of obsessive
      compulsive disorder (OCD), has been proposed as a unique diagnostic entity in DSM
      5. Current models of HD emphasize problems of decision-making, attachment to
      possessions, and poor insight, whereas previous neuroimaging studies have
      suggested abnormalities in frontal brain regions. OBJECTIVE: To examine the
      neural mechanisms of impaired decision making in HD in patients with well-defined
      primary HD compared with patients with OCD and healthy control subjects (HCs).
      DESIGN: We compared neural activity among patients with HD, patients with OCD,
      and HCs during decisions to keep or discard personal possessions and control
      possessions from November 9, 2006, to August 13, 2010. SETTING: Private, not-for
      profit hospital. PARTICIPANTS: A total of 107 adults (43 with HD, 31 with OCD,
      and 33 HCs). MAIN OUTCOME MEASURES: Neural activity as measured by functional
      magnetic resonance imaging in which actual real-time and binding decisions had to
      be made about whether to keep or discard possessions. RESULTS: Compared with
      participants with OCD and HC, participants with HD exhibited abnormal activity in
      the anterior cingulate cortex and insula that was stimulus dependent.
      Specifically, when deciding about items that did not belong to them, patients
      with HD showed relatively lower activity in these brain regions. However, when
      deciding about items that belonged to them, these regions showed excessive
      functional magnetic resonance imaging signals compared with the other 2 groups.
      These differences in neural function correlated significantly with hoarding
      severity and self-ratings of indecisiveness and "not just right" feelings among
      patients with HD and were unattributable to OCD or depressive symptoms.
      CONCLUSIONS: Findings suggest a biphasic abnormality in anterior cingulate cortex
      and insula function in patients with HD related to problems in identifying the
      emotional significance of a stimulus, generating appropriate emotional response,
      or regulating affective state during decision making.

PMID- 22868940
TI  - A new interaction mechanism of LiNH2 with MgH2: magnesium bond.
AB  - Quantum chemical calculations were performed for LiNH2-HMgX (X=H, F, Cl, Br, CH3,
      OH, and NH2) complexes to propose a new interaction mechanism between them. This
      theoretical survey showed that the complexes are stabilized through the
      combinative interaction of magnesium and lithium bonds. The binding energies are
      in the range of 63.2-66.5 kcal mol(-1), i.e., much larger than that of the
      lithium bond. Upon complexation, both Mg-H and Li-N bonds are lengthened.
      Substituents increase Mg-H bond elongation and at the same time decrease Li-N
      bond elongation. These cyclic complexes were characterized with the presence of a
      ring critical point and natural population analysis charges.

PMID- 22868941
TI  - Room temperature formaldehyde sensors with enhanced performance, fast response
      and recovery based on zinc oxide quantum dots/graphene nanocomposites.
AB  - Novel zinc oxide quantum dots (ZnO QDs) decorated graphene nanocomposites were
      fabricated by a facile solution-processed method. ZnO QDs with a size ca. 5 nm
      are nucleated and grown on the surface of the graphene template, and its
      distribution density can be easily controlled by the reaction time and precursor
      concentration. The ZnO QDs/graphene nanocomposite materials enhance formaldehyde
      sensing properties by 4 times compared to pure graphene at room temperature.
      Moreover, the sensors based on the nanocomposites have fast response (ca. 30
      seconds) and recovery (ca. 40 seconds) behavior, excellent room temperature
      selectivity and stability. The gas sensing enhancement is attributed to the
      synergistic effect of graphene and ZnO QDs. The electron transfer between the ZnO
      QDs and the graphene is due to oxidation process of the analyzed gas on the ZnO
      QDs' surface. This proposed gas sensing mechanism is experimentally proved by
      DRIFT spectra results. The ZnO QDs/graphene nanocomposites sensors have potential
      applications for monitoring air pollution, especially for harmful and toxic VOCs
      (volatile organic compounds).

PMID- 22868942
TI  - Exogenous regucalcin suppresses osteoblastogenesis and stimulates adipogenesis in
      mouse bone marrow culture.
AB  - Regucalcin plays a pivotal role in regulating intracellular calcium homeostasis
      and consequently has a profound effect on multiple intracellular signal
      transduction pathways. The regucalcin transgenic rat displays pronounced bone
      loss and hyperlipidemia. Consistent with these effects exogenous regucalcin has
      been shown to promote osteoclastogenesis in mouse bone marrow cultures and to
      suppress the differentiation and mineralization of MC3T3 osteoblast precursors.
      Regucalcin may induce hyperlipidemia in vivo by suppressing osteoblast
      differentiation and stimulating adipogenesis in bone marrow mesenchymal stem
      cells. The present study demonstrates that exogenous regucalcin suppresses
      differentiation to osteoblasts and stimulates adipogenesis in mouse bone marrow
      cell culture ex vivo. Moreover, exogenous regucalcin was found to enhance
      adipogenesis stimulated by insulin which is involved in the extracellular signal
      related kinase pathway in 3T3-L1 adipocytes in vitro.

PMID- 22868944
TI  - Comparison between utility of the Thai Pediatric Quality of Life Inventory 4.0
      Generic Core Scales and 3.0 Cerebral Palsy Module.
AB  - Health-related quality of life (HRQOL) is increasingly being considered in the
      management of patients with various conditions. HRQOL instruments can be broadly
      classified as generic or disease-specific measures. Several generic HRQOL
      instruments in different languages have been developed for paediatric populations
      including the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core
      Scale. This tool and a condition-specific tool, PedsQL 3.0 Cerebral Palsy (CP)
      Module, are widely used in children with CP. No psychometric properties have been
      reported for Thai PedsQL 4.0. Therefore, this study aimed to explore the
      psychometric properties of the Thai version of the PedsQL 4.0 Generic Core Scales
      and compare these with the values for the Thai PedsQL 3.0 CP Module reported
      previously. Thai PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 CP Module were
      completed, respectively, by children with CP and their parents or caregivers
      twice within 2-4 weeks. Respondents were 97 parents or caregivers and 54
      children. Minimal missing data were found in most scales. Acceptable internal
      consistency was supported, except for Emotional, Social, and School Functioning.
      Intraclass correlation coefficients for parent-proxy report and self-report were
      good to excellent (0.625-0.849). The feasibility and reliability of the Thai
      PedsQL 4.0 Generic Core Scales were supported. The Thai PedsQL 3.0 CP Module
      showed higher values for the psychometric properties. Low-to-good correlations
      were found among the scales between the PedsQL 4.0 Generic Core Scales and the
      3.0 CP Module. Both instruments could be used to measure HRQOL for children with
      CP, and may provide different information.

PMID- 22868943
TI  - The lifespan extension effects of resveratrol are conserved in the honey bee and
      may be driven by a mechanism related to caloric restriction.
AB  - Our interest in healthy aging and in evolutionarily conserved mechanisms of
      lifespan extension prompted us to investigate whether features of age-related
      decline in the honey bee could be attenuated with resveratrol. Resveratrol is
      regarded as a caloric restriction mimetic known to extend lifespan in some but
      not all model species. The current, prevailing view is that resveratrol works
      largely by activating signaling pathways. It has also been suggested that
      resveratrol may act as an antioxidant and confer protection against nervous
      system impairment and oxidative stress. To test whether honey bee lifespan,
      learning performance, and food perception could be altered by resveratrol, we
      supplemented the diets of honey bees and measured lifespan, olfactory learning,
      and gustatory responsiveness to sucrose. Furthermore, to test the effects of
      resveratrol under metabolic challenge, we used hyperoxic environments to generate
      oxidative stress. Under normal oxygen conditions, two resveratrol treatments-30
      and 130 MUM-lengthened average lifespan in wild-type honey bees by 38% and 33%,
      respectively. Both resveratrol treatments also lengthened maximum and median
      lifespan. In contrast, hyperoxic stress abolished the resveratrol life-extension
      response. Furthermore, resveratrol did not affect learning performance, but did
      alter gustation. Honey bees that were not fed resveratrol exhibited greater
      responsiveness to sugar, while those supplemented with resveratrol were less
      responsive to sugar. We also discovered that individuals fed a high dose of
      resveratrol-compared to controls-ingested fewer quantities of food under ad
      libitum feeding conditions.

PMID- 22868945
TI  - Facilities of early rehabilitation after stroke in Poland 2010.
AB  - The aim of this work was to survey the contemporary facilities for early
      poststroke rehabilitation in Poland. The main research questions were as follows:
      what is the availability of inpatient rehabilitation for poststroke patients in
      neurological departments and in rehabilitation departments? The growing costs of
      healthcare are encouraging healthcare planners to look for new organizational
      solutions of services that could enable rehabilitation as early as possible after
      disease onset. Early poststroke rehabilitation includes many elements that
      provide for early-onset rehabilitation and its continuation after discharge from
      the stroke unit. Two questionnaires evaluating neurorehabilitation of individuals
      who had stroke were designed and distributed: the first questionnaire was
      distributed to 221 neurological wards and the second questionnaire was
      distributed to 154 rehabilitation departments in Poland. We obtained information
      about delay before admission from neurological wards to rehabilitation
      departments, the number of sessions per day, the time duration of one session,
      the number of sessions per week, the average length of stay in department, the
      methods of outcome measurement, etc. We sent out 375 questionnaires and received
      129 (35%) responses, 78 from neurological wards and 51 from rehabilitation
      departments. Only 25% of all patients were moved from neurological wards to the
      rehabilitation department after stroke (15% directly). Of those moved to
      rehabilitation departments, only 54% were treated early after stroke; that is,
      within 3 months of stroke. Considering that about half of stroke survivors will
      require rehabilitation (30 days after stroke onset), the current facilities of
      early poststroke rehabilitation in Poland cannot meet this need. We should do our
      best to introduce rehabilitation services such as early home-supported discharge
      after stroke, which is currently not available in Poland. Although we have
      focused on resources in Poland, we anticipate that similar patterns may be found
      in other countries in the region.

PMID- 22868939
TI  - Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
AB  - CONTEXT: Recent studies have shown an association between cigarettes per day
      (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
      OBJECTIVE: To determine whether the association between rs16969968 and smoking is
      modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY
      SELECTION: Available genetic studies containing measures of CPD and the genotype
      of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts
      were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted
      the heavy smokers (CPD >20) and light smokers (CPD <=10) with age-at-onset
      information, reducing the sample size to 33,348. Each study was stratified into
      early-onset smokers (age at onset <=16 years) and late-onset smokers (age at
      onset >16 years), and a logistic regression of heavy vs light smoking with the
      rs16969968 genotype was computed for each stratum. Meta-analysis was performed
      within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele
      at rs16969968 who were early-onset smokers were significantly more likely to be
      heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n =
      13,843) than were carriers of the risk allele who were late-onset smokers (OR =
      1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results
      highlight an increased genetic vulnerability to smoking in early-onset smokers.

PMID- 22868946
TI  - Low back pain in 17 countries, a Rasch analysis of the ICF core set for low back
      pain.
AB  - Previous studies indicate that a worldwide measurement tool may be developed
      based on the International Classification of Functioning Disability and Health
      (ICF) Core Sets for chronic conditions. The aim of the present study was to
      explore the possibility of constructing a cross-cultural measurement of
      functioning for patients with low back pain (LBP) on the basis of the
      Comprehensive ICF Core Set for LBP and to evaluate the properties of the ICF Core
      Set. The Comprehensive ICF Core Set for LBP was scored by health professionals
      for 972 patients with LBP from 17 countries. Qualifier levels of the categories,
      invariance across age, sex and countries, construct validity and the ordering of
      the categories in the components of body function, body structure, activities and
      participation were explored by Rasch analysis. The item-trait chi2-statistics
      showed that the 53 categories in the ICF Core Set for LBP did not fit the Rasch
      model (P<0.001). The main challenge was the invariance in the responses according
      to country. Analysis of the four countries with the largest sample sizes
      indicated that the data from Germany fit the Rasch model, and the data from
      Norway, Serbia and Kuwait in terms of the components of body functions and
      activities and participation also fit the model. The component of body functions
      and activity and participation had a negative mean location, -2.19 (SD 1.19) and 
      2.98 (SD 1.07), respectively. The negative location indicates that the ICF Core
      Set reflects patients with a lower level of function than the present patient
      sample. The present results indicate that it may be possible to construct a
      clinical measure of function on the basis of the Comprehensive ICF Core Set for
      LBP by calculating country-specific scores before pooling the data.

PMID- 22868949
TI  - Colloidal nanoparticle clusters: functional materials by design.
AB  - Significant advances in colloidal synthesis made in the past two decades have
      enabled the preparation of high quality nanoparticles with well-controlled sizes,
      shapes, and compositions. It has recently been realized that such nanoparticles
      can be utilized as 'artificial atoms' for building new materials which not only
      combine the size- and shape-dependent properties of individual nanoparticles but
      also create new collective properties by taking advantage of their
      electromagnetic interactions. The controlled clustering of nanoparticle building
      blocks into defined geometric arrangements opens a new research area in materials
      science and as a result much interest has been paid to the creation of secondary
      structures of nanoparticles, either by direct solution growth or self-assembly
      methods. In this tutorial review, we introduce recently developed strategies for
      the creation and surface modification of colloidal nanoparticle clusters,
      demonstrate the new collective properties resulting from their secondary
      structures, and highlight several of their many important technological
      applications ranging from photonics, separation, and detection, to multimodal
      imaging, energy storage and transformation, and catalysis.

PMID- 22868948
TI  - From infancy to pregnancy: birth weight, body mass index, and the risk of
      gestational diabetes.
AB  - Obesity is a risk factor for gestational diabetes, whereas the role of the
      mother's birth weight is more uncertain. We aimed to investigate the combined
      effect of mothers' birth-weight-for-gestational-age and early pregnancy Body Mass
      Index (BMI) in relation to risk of gestational diabetes. Between 1973 and 2006,
      we identified a cohort of 323,083 women included in the Swedish Medical Birth
      Register both as infants and as mothers. Main exposures were mothers' birth
      weight-for-gestational-age (categorized into five groups according to deviation
      from national mean birth weight) and early pregnancy BMI (classified according to
      WHO). Rates of gestational diabetes increased with adult BMI, independently of
      birth-weight-for-gestational-age. However, compared to women with appropriate
      birth-weight-for-gestational-age [appropriate-for-gestational age (AGA); -1 to +1
      SD] and BMI (<25.0), women with obesity class II-III (BMI >= 35.0) had an
      adjusted odds ratio (OR) of 28.7 (95 % confidence interval, CI 17.0-48.6) for
      gestational diabetes if they were born small-for-gestational-age [small for
      gestational age (SGA); <-2SD], OR = 20.3 (95 % CI 11.8-34.7) if born large-for
      gestational-age [large-for-gestational-age (LGA); >2SD], and OR = 10.4 (95 % CI
      8.4-13.0) if born AGA. Risk of gestational diabetes is not only increased among
      obese women, but also among women born SGA and LGA. Severely obese women born
      with a low or a high birth-weight-for-gestational-age seem more vulnerable to the
      development of gestational diabetes compared to normal weight women. Normal pre
      pregnancy BMI diminishes the increased risk birth size may confer in terms of
      gestational diabetes. Therefore, the importance of keeping a healthy weight
      cannot be overemphasized.

PMID- 22868947
TI  - Passing the baton: a grounded practical theory of handoff communication between
      multidisciplinary providers in two Department of Veterans Affairs outpatient
      settings.
AB  - BACKGROUND: Handoffs are communication processes that enact the transfer of
      responsibility between providers across clinical settings. Prior research on
      handoff communication has focused on inpatient settings between provider teams
      and has emphasized patient safety. This study examines handoff communication
      within multidisciplinary provider teams in two outpatient settings. OBJECTIVE: To
      conduct an exploratory study that describes handoff communication among
      multidisciplinary providers, to develop a theory-driven descriptive framework for
      outpatient handoffs, and to evaluate the strengths and weaknesses of different
      handoff types. DESIGN & SETTING: Qualitative, in-depth, semi-structured
      interviews with 31 primary care, mental health, and social work providers in two
      Department of Veterans Affairs (VA) Medical Center outpatient clinics. APPROACH:
      Audio-recorded interviews were transcribed and analyzed using Grounded Practical
      Theory to develop a theoretical model of and a descriptive framework for handoff
      communication among multidisciplinary providers. RESULTS: Multidisciplinary
      providers reported that handoff decisions across settings were made spontaneously
      and without clear guidelines. Two situated values, clinic efficiency and patient
      centeredness, shaped multidisciplinary providers' handoff decisions. Providers
      reported three handoff techniques along a continuum: the electronic handoff,
      which was the most clinically efficient; the provider-to-provider handoff, which
      balanced clinic efficiency and patient-centeredness; and the collaborative
      handoff, which was the most patient-centered. Providers described handoff choice
      as a practical response to manage constituent features of clinic efficiency
      (time, space, medium of communication) and patient-centeredness (information
      continuity, management continuity, relational continuity, and social
      interaction). We present a theoretical and descriptive framework to help
      providers evaluate differential handoff use, reflect on situated values guiding
      clinic communication, and guide future research. CONCLUSIONS: Handoff
      communication reflected multidisciplinary providers' efforts to balance clinic
      efficiency with patient-centeredness within the constraints of day-to-day
      clinical practice. Evaluating the strengths and weaknesses among alternative
      handoff options may enhance multidisciplinary provider handoff decision-making
      and may contribute to increased coordination and continuity of care across
      outpatient settings.

PMID- 22868950
TI  - Three- and four-dimensional HDlive rendering images of normal and abnormal
      fetuses: pictorial essay.
AB  - BACKGROUND: Our objective is to present our experience of normal embryonic
      development and fetal anatomy and fetal anomalies reconstructed employing the
      three-dimensional (3D) and four-dimensional (4D) HDlive rendering mode. METHODS:
      A total of 18 normal embryos and fetuses and 21 abnormal fetuses (one case each
      of thoracic meningocele, thickened nuchal translucency, multicystic dysplastic
      kidney, gastroschisis, omphalocele, and ovarian cyst, five of hydrops fetalis,
      three of skeletal abnormality, three of chromosome abnormality, two of cystic
      hygroma, and two of amniotic band syndrome) at 7-36 weeks' gestation were studied
      using the 3D/4D HDlive rendering mode. RESULTS: In normal fetuses, marked
      embryonic development with advancing gestation was clearly shown in the first
      trimester of pregnancy, and various realistic facial expressions were noted in
      the second and third trimesters. In abnormal fetuses, anatomically realistic
      features such as gross specimens were obtained. In particular, 3D/4D HDlive
      provides new, realistic sensations for the diagnosis of amniotic band syndrome,
      skeletal abnormalities, and facial abnormalities. CONCLUSION: 3D/4D HDlive
      rendering images seem to be more readily discernible than those obtained by
      conventional 3D/4D sonography. 3D/4D HDlive may be an important modality in
      future embryonic research, fetal neurobehavioral assessment, and the evaluation
      of fetal anomalies.

PMID- 22868951
TI  - Reduce repayment rates to 0.5%.

PMID- 22868952
TI  - Why did the BMJ publish such a biased article?

PMID- 22868953
TI  - Advice to avoid low carbohydrate-high protein diets is not evidence based.

PMID- 22868956
TI  - Sudden death in young men from South East Asia and the Pacific rim.

PMID- 22868957
TI  - The GMC's paradoxical behaviour.

PMID- 22868958
TI  - What are we being trained for?

PMID- 22868959
TI  - Box ticking is a waste of time.

PMID- 22868960
TI  - Rural areas may benefit most.

PMID- 22868961
TI  - Whole System Demonstrator trial: policy, politics, and publication ethics.

PMID- 22868962
TI  - A step too far.

PMID- 22868963
TI  - Fluoroquinolones and theophylline can also lower the seizure threshold.

PMID- 22868965
TI  - Massachusetts plans to cut healthcare costs.

PMID- 22868967
TI  - Biclonal and biallelic deletions occur in 20% of B-ALL cases with IKZF1
      mutations.

PMID- 22868966
TI  - Quantitative pilomotor axon reflex test: a novel test of pilomotor function.
AB  - BACKGROUND: Cutaneous autonomic function can be quantified by the assessment of
      sudomotor and vasomotor responses. Although piloerector muscles are innervated by
      the sympathetic nervous system, there are at present no methods to quantify
      pilomotor function. OBJECTIVE: To quantify piloerection using phenylephrine
      hydrochloride in humans. DESIGN: Pilot study. SETTING: Hospital-based study.
      PARTICIPANTS: Twenty-two healthy volunteers (18 males,4 females) aged 24 to 48
      years participated in 6 studies. INTERVENTIONS: Piloerection was stimulated by
      iontophoresis of 1% phenylephrine. Silicone impressions of piloerection were
      quantified by number and area. The direct and indirect responses to phenylephrine
      iontophoresis were compared on both forearms after pre treatment to topical and
      subcutaneous lidocaine and iontophoresis of normal saline. RESULTS: Iontophoresis
      of phenylephrine induced piloerection in both the direct and axon reflex-mediated
      regions, with similar responses in both arms. Topical lidocaine blocked axon
      reflex-mediated piloerection post-iontophoresis (mean [SD], 66.6 [19.2] for
      control impressions vs 7.2 [4.3] for lidocaine impressions;P.001). Subcutaneous
      lidocaine completely blocked piloerection.The area of axon reflex-mediated
      piloerection was also attenuated in the lidocaine-treated region
      postiontophoresis (mean [SD], 46.2 [16.1]cm2 vs 7.2 [3.9]cm2; P.001).
      Piloerection was delayed in the axon reflex region compared with the direct
      region. Normal saline did not cause piloerection. CONCLUSIONS: Phenylephrine
      provoked piloerection directly and indirectly through an axon reflex-mediated
      response that is attenuated by lidocaine. Piloerection is not stimulated by
      iontophoresis of normal saline alone.The quantitative pilomotor axon reflex test
      (QPART) may complement other measures of cutaneous autonomic nerve fiber
      function.

PMID- 22868968
TI  - BTG1 deletions do not predict outcome in Down syndrome acute lymphoblastic
      leukemia.

PMID- 22868969
TI  - Ex vivo expansion of normal and chronic myeloid leukemic stem cells without
      functional alteration using a NUP98HOXA10homeodomain fusion gene.
AB  - HOX genes have been implicated as regulators of normal and leukemic stem cell
      functionality, but the extent to which these activities are linked is poorly
      understood. Previous studies revealed that transduction of primitive mouse
      hematopoietic cells with a NUP98HOXA10homeodomain (NA10HD) fusion gene enables a
      subsequent rapid and marked expansion in vitro of hematopoietic stem cell numbers
      without causing their transformation or deregulated expansion in vivo. To
      determine whether forced expression of NA10HD in primitive human cells would have
      a similar effect, we compared the number of long-term culture-initiating cells
      (LTC-ICs) present in cultures of lenti-NA10HD versus control virus-transduced
      CD34(+) cells originally isolated from human cord blood and chronic phase (CP)
      chronic myeloid leukemia (CML) patients. We found that NA10HD greatly increases
      outputs of both normal and Ph(+)/BCR-ABL(+) LTC-ICs, and this effect is
      particularly pronounced in cultures containing growth factor-producing feeders.
      Interestingly, NA10HD did not affect the initial cell cycle kinetics of the
      transduced cells nor their subsequent differentiation. Moreover, immunodeficient
      mice repopulated with NA10HD-transduced CP-CML cells for more than 8 months
      showed no evidence of altered behavior. Thus, NA10HD provides a novel tool to
      enhance both normal and CP-CML stem cell expansion in vitro, without apparently
      altering other properties.

PMID- 22868970
TI  - Intraoperative local insufflation of warmed humidified CO2 increases open wound
      and core temperatures: a randomized clinical trial.
AB  - BACKGROUND: The open surgical wound is exposed to cold dry ambient air, resulting
      in substantial heat loss through radiation, evaporation, and convection. At the
      same time, anesthesia decreases the patient's core temperature. Despite
      preventive measures, mild intraoperative hypothermia has been associated with
      postoperative morbidity. We hypothesized that local insufflation of warmed
      humidified carbon dioxide (CO(2)) would maintain wound and core temperature.
      METHODS: Eighty patients undergoing open colon surgery were randomized to
      standard warming measures, or to additional local wound insufflation of warmed
      (30  degrees C) humidified (93 % rH) CO(2) via a gas diffuser. Surface
      temperature of the open abdominal wound was measured with a heat-sensitive
      infrared camera, and core temperature was measured with an ear thermometer.
      RESULTS: Mean operative time was 219 +/- 104 and 205 +/- 85 min in the CO(2)
      group and the control group, respectively (p = 0.550). Clinical variables did not
      differ significantly between the groups. The median wound area and wound edge
      temperatures were 1.2  degrees C (p < 0.001) and 1.0  degrees C (p = 0.002)
      higher in the CO(2) group, respectively, than in the control group. The mean core
      temperature after intubation was the same (35.9  degrees C) in both groups, but
      at end of surgery core temperature in the two groups differed, with a mean of
      36.2 +/- 0.5  degrees C in the CO(2) group and a mean of 35.8 +/- 0.5  degrees C
      in the control group (p = 0.003). CONCLUSIONS: Insufflation of warmed, humidified
      CO(2) in an open surgical wound cavity prevents intraoperative decrease in
      surgical wound temperature as well as core temperature.

PMID- 22868971
TI  - Antethoracic pedicled jejunum reconstruction with the supercharge technique for
      esophageal cancer.
AB  - BACKGROUND: Gastric tube is the first choice as an esophageal substitute for
      reconstruction after esophagectomy. Colon or jejunum is selected for patients in
      whom stomach cannot be used. Colon interposition is reported to have a high
      incidence of anastomotic leakage and mortality. For safer surgical treatment, the
      authors adopted supercharged pedicle jejunum reconstruction as the operation of
      choice in patients with esophageal cancer who had no stomach to use as an
      esophageal substitute. The aim of this study was to review our experience with
      this technique. METHODS: From 2003 to 2009, esophagectomy and antethoracic
      pedicled jejunum reconstruction with the supercharge technique was performed in
      27 patients with esophageal cancer at the Department of Gastroenterological
      Surgery (Surgery II), Nagoya University Hospital. Medical records of these 27
      patients were retrospectively reviewed to determine demographic data, diagnosis,
      functional results, and perioperative course. RESULTS: Median operating time,
      blood loss, hospital stay, and duration of enteral feeding were 636 min (range
      454-856 min), 580 ml (range 208-1959 ml), 27 days (range 16-72 days), and 80 days
      (range 26-1740 days), respectively. There were no in-hospital deaths. Anastomotic
      leakage occurred in two patients and was successfully managed conservatively. In
      2 of 27 patients, the pedicled jejunum was of insufficient length, and additional
      procedures were needed to complete the anastomosis. CONCLUSIONS: Although
      antethoracic pedicled jejunum reconstruction with the supercharge technique is
      technically demanding, it is a reliable technique and contributes to successful
      reconstruction after esophagectomy for patients in whom stomach is not available
      for reconstruction.

PMID- 22868972
TI  - [Long term effectiveness of methadone maintenance treatments in persons with
      addiction to opiates].
AB  - There is no large prospective cohort studies using different therapeutic doses
      and standardized distal outcomes, however there is a fair amount of evidence on
      the effectiveness of methadone as a long-term treatment for the addiction to
      opiates. Strengths include less illegal drug use, decreased criminal activity and
      better general functioning. Also physical and mental health seems to be more
      preserved and recovered. Since patients undergoing methadone treatment exhibit
      diminished likelihood of suffering from cardiovascular conditions, HIV, HCV, HBV
      and other infections, and lesser psychiatric comorbidity. This Editorial intends
      to define and guide the therapeutic statement to address the management of
      persons with opiate abuse or dependence. These proposals have been grounded in
      the main long-term studies, systematic analysis and meta-analytic approaches on
      the effectiveness of methadone. Thereby it is recommended, with the maximum level
      of evidence, methadone maintenance treatments in spite of its weaknesses (ie.
      Toxicity, cardiovascular risk, sedation problems and cognitive impairment),
      considering the clinical history, general health status, and willingness and
      preferences of the patient.

PMID- 22868973
TI  - Human enhancement drugs and the pursuit of perfection.
AB  - The emerging threat to public health posed by the use of human enhancement drugs
      has remained largely unrecognised. In attempts to become stronger, happier or
      smarter, or to look thinner, younger or more beautiful, people are turning to a
      diverse range of pharmaceuticals. The widespread availability of drugs with the
      potential to improve human attributes, appearance and abilities has generated a
      new and growing audience of users. Unlike users of drugs such as heroin, cocaine
      etc, users of human enhancement drugs do not necessarily perceive themselves as
      'drug users'. Those attracted to these drugs may have little or no knowledge or
      understanding of the physical or psychological harm associated with these
      substances or their potential for addiction. In addition to the potent effects of
      many human enhancement drugs, there are considerable risks associated to the
      clandestine nature of the market. The growing number of untested, banned or
      adulterated drugs and the lack of safeguards and quality assurance in the illicit
      manufacturing process has resulted in serious harms and fatalities. The ease with
      which pharmaceuticals can be manufactured and distributed, combined with the
      significant profits that can be made from the illicit market, has resulted in a
      growing challenge for policy makers and health systems in many countries. This
      editorial aims to raise awareness of this emerging drugs situation and provide a
      brief overview of some of the drugs and their associated risks.

PMID- 22868974
TI  - [Efficiency of two motivational interventions for adolescent smokers (brief and
      intensive) conducted in high schools].
AB  - We set out to determine the efficiency of two motivational interventions (brief
      and intensive) in adolescent smokers, based on obtaining cognitive dissonance and
      seeking to help them stop smoking. A multicenter randomized experimental study
      was carried out at five high schools. Individual anti-smoking interventions were
      applied at the schools, the participants being adolescent smokers (<= 20 years)
      who wished to quit smoking. Exclusion criteria were use of anti-smoking drugs,
      severe psychiatric illness and pregnancy. Informed consent was obtained and a
      questionnaire recorded demographic variables and alcohol/tobacco/other drug use.
      Two motivational interventions were carried out at each school by GP, in
      accordance with a stratified randomization procedure: intensive (four sessions,
      progressive reduction of smoking) and brief (single session, immediate cessation
      of smoking). Smoking abstinence was confirmed by co-oximetry at 1, 6 and 12
      months after the intervention, with analysis by intention to treat. A total of 92
      adolescents participated, with a mean age of 15.4 +/- 1.0 years; no differences
      at the beginning of the interventions: daily smokers accounted for 82% of the
      sample, with low dependence (62%) and moderate-high motivation to quit smoking
      (88%). Seventy-eight per cent used alcohol and 21% other drugs. Family
      functioning and social support were normal in the majority. 47% received the
      intensive intervention. Abstinence was achieved by 64% +/- 5.0 by the first month
      (20% better in intensive intervention), 42% +/- 5.2 by the sixth month and 27% +/
      4.6 by the twelfth month (without differences). The brief intervention appears
      to be more efficient, while more research is needed to determine the profile of
      those adolescents who would benefit from intensive intervention.

PMID- 22868975
TI  - Psychiatric morbidity among cocaine and heroin users in the community.
AB  - Drug abuse is a serious public health problem. Moreover, co-occurring mental
      health and substance abuse disorders are common among drug users. This paper
      examines psychiatric disorders of young cocaine and heroin users using the World
      Mental Health Composite International Diagnostic Interview (WMH-CIDI). A cohort
      of 1266 young (18-30 years) current regular cocaine (705) and heroin (561) users
      were recruited outside the health services in Barcelona, Madrid and Seville,
      Spain. The WMH-CIDI was used to evaluate mental disorders; the Severity of
      Dependence Scale (SDS) measured the degree of dependence; and the Duke-UNC
      Functional Social Support Questionnaire (FSSQ) assessed social support, in a
      crosssectional study design. About 43% was diagnosed with a lifetime mental
      disorder. The most common diagnoses were depression (37.5%) and specific phobia
      (6.8%). During the last 12 months, prevalence rates were also slightly higher in
      heroin group (26.4%) than in cocaine cohort (21.7%). Every day cocaine
      consumption, having unstable living conditions and low social support were
      variables highly associated with psychiatric morbidity in cocaine cohort. In
      heroin cohort, earning money through illegal activities was associated with
      psychiatric morbidity, while the moderate use of alcohol acted as a protective
      factor for mental pathology. Morbidity was associated to having received
      psychiatric/psychological treatment during the last 12 months in both cohorts.
      This study has shown a relatively high prevalence of psychiatric morbidity in
      cocaine and heroin users recruited in non-clinical settings. Future studies
      examining differences between cocaine and heroin patterns of consumption
      associated with mental diseases are necessary.

PMID- 22868976
TI  - The effect of the school-based unplugged preventive intervention on tobacco use
      in the Czech Republic.
AB  - Unplugged is a school prevention programme widely implemtend in Europe, with some
      positive evaluations. This research aims to measure the impact of this program on
      tobacco use by means of the lifetime and last-30-day tobacco use prevalence
      indicators and verify the duration of the intervention's measurable effect over
      time. The study was designed as a randomised controlled prevention trial. The
      intervention is based on the Comprehensive Social Influence model and consists of
      12 lessons delivered to Czech adolescents in the 2007-2008 academic year. The
      prevalence indicators were calculated to assess the differences between the
      experimental (N = 914) and control (N = 839) groups on each outcome 1, 3, 12, 15,
      and 24 months after the end of the intervention. Data were collected using the
      2003 version of the ESPAD questionnaire. As regards the 30-day smoking prevalence
      indicator, the tests performed after the completion of the intervention showed
      statistically significant differences between both groups in favour of the
      experimental one. Two years after the completion of the intervention the
      experimental and control groups showed 30-day prevalence rates of 26.7% and
      33.1%, respectively (p = .01). The progression of smoking in the 30-day
      prevalence among the experimental group was significantly slower than that among
      the control group over the period of time. The differences in the lifetime
      prevalence rates were not statistically significant. The implementation of
      Unplugged resulted in a statistically significant measurable positive effect on
      tobacco use in Czech adolescents.

PMID- 22868977
TI  - Subtypes of adolescents with substance use disorders and psychiatric comorbidity
      using cluster and discriminant analysis of MMPI-A profiles.
AB  - The main aim of this study was to replicate and extend previous results on
      subtypes of adolescents with substance use disorders (SUD), according to their
      Minnesota Multiphasic Personality Inventory for adolescents (MMPI-A) profiles.
      Sixty patients with SUD and psychiatric comorbidity (41.7% male, mean age = 15.9
      years old) completed the MMPI-A, the Teen Addiction Severity Index (T-ASI), the
      Child Behaviour Checklist (CBCL), and were interviewed in order to determine
      DSMIV diagnoses and level of substance use. Mean MMPI-A personality profile
      showed moderate peaks in Psychopathic Deviate, Depression and Hysteria scales.
      Hierarchical cluster analysis revealed four profiles (acting-out, 35% of the
      sample; disorganized-conflictive, 15%; normative-impulsive, 15%; and deceptive
      concealed, 35%). External correlates were found between cluster 1, CBCL
      externalizing symptoms at a clinical level and conduct disorders, and between
      cluster 2 and mixed CBCL internalized/externalized symptoms at a clinical level.
      Discriminant analysis showed that Depression, Psychopathic Deviate and
      Psychasthenia MMPI-A scales correctly classified 90% of the patients into the
      clusters obtained.

PMID- 22868978
TI  - [Changes in core beliefs associated with addiction among substance-dependent
      patients with vs. without comorbid personality disorders].
AB  - The aims of this study were: 1) To evaluate the predictive ability of cognitive
      beliefs about craving and alcohol use during treatment; and 2) To examine the
      course of cognitive beliefs, over a nine-month follow-up, as a function of
      comorbidity with personality disorders (PDs). Participants in the study were
      sixty-five alcohol-dependent patients initiating treatment at the Provincial Drug
      Dependence Centre in Granada (Spain), 56.4% of whom had comorbid personality
      disorder. We administered the "Questionnaire on beliefs related to addiction and
      craving", taking number of alcohol-use episodes during treatment and degree of
      psychological adjustment as outcome variables. We used linear regression models
      to analyze the relation between questionnaire items and outcome variables, and
      related-samples t-tests to examine the course of beliefs throughout the follow
      up. Results indicate that it is feasible to reliably measure a range of
      dysfunctional beliefs associated with addiction, that the degree of
      identification with these beliefs significantly predicts craving and alcohol use
      during treatment, and that the course of identification with these beliefs is
      considerably more irregular in alcohol-dependent individuals with comorbid PDs.

PMID- 22868979
TI  - [Epidemiological study of acute poisoning cases treated at a Galician hospital
      between 2005 and 2008].
AB  - A descriptive retrospective study of acute intoxication cases registered at the
      Complexo Hospitalario de Pontevedra (CHOP) between January 2005 and December 2008
      was performed to find out the number and types of poisoning cases treated, their
      distribution according to patient's sex and age, chronology, type of toxic agents
      involved, intentionality, history, symptoms, clinical development, treatment and
      toxicological analysis used for diagnosis. Data were recorded using Clinica and
      IANUS software and consulting all paper records of patients with symptoms of
      poisoning. Data from a total of 1893 patients with a mean age of 35.6 +/- 17.6
      years (66% men) were included. Highest rates of poisoning were recorded on
      Saturdays and Sundays during the summer months (June, July and August). Drugs of
      abuse were the most common toxic agents (70.4%), ethyl alcohol accounting for 61%
      of these cases, which often involved males and with people with high degrees of
      dependency. In second place was poisoning resulting from the abuse of medical
      drugs, more commonly associated with females, and involving benzodiazepines in
      73.2% of cases. The majority of these intoxications were intentional, and suicide
      attempts accounted for 18.8%. The problems most commonly resulting from the
      poisoning were neurological, and mortality rate was just 0.2%.

PMID- 22868980
TI  - Estimation of alcohol attributable fraction of mortality in Russia.
AB  - Accumulated research evidence suggests that alcohol is a major contributor to
      premature deaths toll in Russia. The aim of the present study was to estimate the
      premature adult mortality attributable to alcohol abuse in Russia on the basis of
      aggregate-level data of all-cause mortality and alcohol consumption. With this
      purpose age-standardized sex-specific male and female all-cause mortality data
      for the period 1980-2005 and data on overall alcohol consumption were analyzed by
      means ARIMA time series analysis. As a result alcohol consumption was
      significantly associated with both male and female all-cause mortality rates: a 1
      liter increase in overall alcohol consumption would result in a 3.9% increase in
      the male mortality rate and in 2.4% increase in female mortality rate. The
      results of the analysis also suggest that 41.1% of all male deaths and 27.8%
      female deaths in Russia could be attributed to alcohol. We can conclude that
      alcohol is a major contributor to the high mortality rate in Russian Federation.
      Therefore prevention of alcohol-attributable harm should be a major public health
      priority in Russia.

PMID- 22868981
TI  - [How does family disorganization influence children's drug use? A review].
AB  - It is well known that various aspects of family functioning can influence
      children's drug use, both by promoting resilience and by increasing the risk of
      use. This review examines studies published in the last 30 years about the
      influence of family disorganization on children's drug use. Based on the results,
      we consider that disorganised families (charactirezed by parents' mental illness,
      parents' substance use and/or non-intact families) are more likely to have
      children who are drug users, both legal and illegal. Finally, we stress the need
      to improve the conceptualization of family disorganization and its assessment,
      and point out other methodological limitations found in the empirical studies
      reviewed.

PMID- 22868982
TI  - [Relapse in cocaine addiction: a review].
AB  - Relapse remains a common problem in disorders related to cocaine use. The aim of
      this paper is to review recent research data on the variables and factors related
      to relapse in cocaine-dependent individuals. We carried out a systematic search
      for studies including variables related to cocaine use in some of the most
      important national and international databases: PubMed, ISI Web of Knowledge, The
      Cochrane Library, IME and ISOC. To locate the latest research data, the search
      covered the period January 2000 to July 2011. Many and varied factors and
      variables identified with some predictive power were identified, notably
      psychosocial problems, negative emotional states, anxiety, self-efficacy,
      psychopathological comorbidity, addictive severity, and several variables related
      to the treatment process. Knowledge about the relapse process has increased
      considerably in recent years, but although the influence of certain factors on
      relapse in cocaine use now seems clear, specific research is still scarce and
      inconclusive.

PMID- 22868983
TI  - Maxillofacial injuries due to work-related accidents in the North West of Italy.
AB  - INTRODUCTION: The aim of this study was to assess the incidence and patterns of
      work-related maxillofacial injuries, identifying worker categories with a high
      risk of injury. MATERIAL AND METHODS: From a systematic computer-assisted
      database that has continuously recorded patients hospitalized with maxillofacial
      fractures, only patients with work-related injuries were considered. Occupation,
      mechanism of injury, and demographic and clinical data were analyzed. RESULTS:
      Work-related facial injuries represented the fifth most common cause of injury,
      with a percentage of 6.3 %. Maxillofacial fractures were most often seen in
      construction workers (37.9 %). The middle third was involved in 67 % of the
      cases; the mandible was the most frequently injured site. CONCLUSIONS: Work
      related maxillofacial trauma is rare, but it is often complex and challenging as
      Facial Injury Severity Scale values show. In agreement with the few published
      reports, construction workers, together with farm and forestry workers, are at
      the highest risk of injuries, mainly because of struck by a thrown, projected, or
      falling object.

PMID- 22868984
TI  - Incomplete removal of basal cell carcinoma: what is the value of further surgery?
AB  - INTRODUCTION: Surgical management of skin cancer is an important part of modern
      maxillofacial surgery. The common tumours treated are squamous cell carcinoma,
      malignant melanoma and some benign lesions, but the largest group of tumours are
      the basal cell carcinomas. Although only locally aggressive, if they are not
      completely removed, recurrence may occur and be troublesome, especially in the
      head and neck. Even in this region, incomplete excision is uncommon, less than 20
      %, but management of positive margins remains controversial. This review
      evaluates the effectiveness of a further surgical intervention after a positive
      margin. MATERIALS AND METHODS: A retrospective audit was undertaken to determine
      the rate of positive margins within the unit and subsequently the percentage of
      residual tumour found in any secondary excisions. RESULTS: The results show that
      in a sample of 247 patients, 11 % had positive peripheral margins. A second
      excision only showed that 36 % had any evidence of residual tumour. DISCUSSION:
      The study raises the question of the value of further surgery. Finally, the
      authors suggest a more focused approach to the finding of a positive margin
      before the patient is offered more treatment.

PMID- 22868985
TI  - Evaluation of pressure-controlled ventilation concepts during cardiopulmonary
      resuscitation (CPR) in dental chairs.
AB  - BACKGROUND: Infrequent training of lay rescuers in cardiopulmonary resuscitation
      may lead to stomach inflation during ventilation of the unsecured airway. This is
      caused by a pressure loss of the lower oesophageal sphincter (LOSP) after onset
      of cardiac arrest. To minimise the risk of stomach inflation, the SMART BAG(r)
      (SB), a disposable flow-limited bag-valve-mask resuscitator, has been designed.
      Aim The aim of this study was to evaluate the occurrence of stomach inflation by
      use of SB in comparison to two other ventilation devices with respect to the
      ventilation capability. METHOD: An Easy Grip(r) disposable bag-valve-mask
      resuscitator (EG), an SB and an EG with an interposed T-piece attached to a 0.5 l
      reservoir bag (EG/R) were compared in a manikin ventilation training setting.
      Fourteen dentists performed ventilations on a Mini Ventilation Training Analyzer
      using EG, SB and EG/R with lung compliance (LC) and LOSP being adjusted to 700
      ml/kPa and 1.5 kPa (best case) and 500 ml/kPa and 0.5 kPa (worst case) in a
      randomised order. RESULTS: Sufficient tidal volumes were obtained by use of all
      the three test devices regardless of LC or LOSP. No statistical differences were
      detected between the use of SB and EG/R. Using EG led to statistically larger
      volumes. Stomach inflation could only be avoided using SB and EG/R at a high LOSP
      regardless of LC. CONCLUSION: Even in the worst case scenario, use of SB and EG/R
      administered sufficient tidal volumes with a significantly smaller stomach
      inflation compared to EG. Combination of standard bag-valve devices with a
      reservoir bag may provide similar protection from gastric inflation as the SMART
      BAG(r).

PMID- 22868986
TI  - Occurrence of dental avulsion and associated injuries in patients with facial
      trauma over a 9-year period.
AB  - INTRODUCTION: This retrospective study aimed to assess the occurrence of dental
      avulsions in patients with facial trauma over a 9-year period. MATERIALS AND
      METHODS: Data was collected from records of patients attended to at the Division
      of Oral and Maxillofacial Surgery at Piracicaba Dental School-State University of
      Campinas, Piracicaba (SP), Brazil. RESULTS: Two hundred three patients with 387
      avulsed teeth were evaluated, the central incisors being the most common teeth
      involved (42 % of permanent and 61 % of primary teeth). Thirty-four percent of
      the cases occurred on weekends, mainly on Saturdays (20 %) and the distribution
      in relation to the time of year was similar with slight peaks in January. The
      most prevalent associated dentoalveolar injury was lateral luxation (26 %) and 19
      % of the patients presented with an associated facial fracture. The most common
      sign presented was laceration (23 %), and the main symptoms found were pain (58
      %). Associated general trauma was present in 139 patients (68 %), and the most
      prevalent was the upper limb (41 %). DISCUSSION: Special emphasis should be given
      not only to diagnosis and treatment of dental avulsion but for prevention, too.
      An understanding of the etiology, severity, and distribution of associated
      traumatic injuries can help for future studies and for an effective prevention of
      these injuries.

PMID- 22868987
TI  - Oocyte-specific linker histone H1foo is an epigenomic modulator that decondenses
      chromatin and impairs pluripotency.
AB  - Mammalian oocytes contain the histone H1foo, a distinct member with low sequence
      similarity to other members in the H1 histone family. Oocyte-specific H1foo
      exists until the second embryonic cell stage. H1foo is essential for oocyte
      maturation in mice; however, the molecular function of this H1 subtype is
      unclear. To explore the function of H1foo, we generated embryonic stem (ES) cells
      ectopically expressing H1foo fused to an EGFP (H1foo-ES). Interestingly, ectopic
      expression of H1foo prevented normal differentiation into embryoid bodies (EBs).
      The EB preparations from H1foo-ES cells maintained the expression of pluripotent
      marker genes, including Nanog, Myc and Klf9, and prevented the shift of the DNA
      methylation profile. Because the short hairpin RNA-mediated knockdown of H1foo
      EGFP recovered the differentiation ability, H1foo was involved in preventing
      differentiation. Furthermore, ChIP analysis revealed that H1foo-EGFP bound
      selectively to a set of hypomethylated genomic loci in H1foo-ES, clearly
      indicating that these loci were targets of H1foo. Finally, nuclease sensitivity
      assay suggested that H1foo made these target loci decondensed. We concluded that
      H1foo has an impact on the genome-wide, locus-specific epigenetic status.

PMID- 22868988
TI  - Improving the heart failure readmission rate at an urban medical center.

PMID- 22868989
TI  - Self-report is a primary source of information about pain, but it is not
      infallible: a comment on "response to Voepel-Lewis's letter to the editor,
      'bridging the gap between pain assessment and treatment: time for a new
      theoretical approach?'".

PMID- 22868990
TI  - Time management strategies for research productivity.
AB  - Researchers function in a complex environment and carry multiple role
      responsibilities. This environment is prone to various distractions that can
      derail productivity and decrease efficiency. Effective time management allows
      researchers to maintain focus on their work, contributing to research
      productivity. Thus, improving time management skills is essential to developing
      and sustaining a successful program of research. This article presents time
      management strategies addressing behaviors surrounding time assessment, planning,
      and monitoring. Herein, the Western Journal of Nursing Research editorial board
      recommends strategies to enhance time management, including setting realistic
      goals, prioritizing, and optimizing planning. Involving a team, problem-solving
      barriers, and early management of potential distractions can facilitate
      maintaining focus on a research program. Continually evaluating the effectiveness
      of time management strategies allows researchers to identify areas of improvement
      and recognize progress.

PMID- 22868991
TI  - Sexual medicine: Combined contraceptives--which delivery route is best?

PMID- 22868993
TI  - Sexual medicine: Pain and pleasure--reconstruction after female genital
      mutilation.

PMID- 22868994
TI  - Sexual medicine: Can pelvic measurements predict gender identity disorder?

PMID- 22868995
TI  - Prostate cancer: Lessons from PIVOT lost in media hype.

PMID- 22868998
TI  - Sexual medicine: Increased PDE5 levels in a mouse model of type 2 diabetes.

PMID- 22868999
TI  - Prostate cancer: Radioactive gold nanoparticles show promise for tumour
      shrinkage.

PMID- 22869003
TI  - Ets-1 transcription is required in tissue factor driven microvessel formation and
      stabilization.
AB  - Tissue factor (TF) has well-recognized roles as initiator of blood coagulation as
      well as an intracellular signaling receptor. TF signaling regulates gene
      transcription and protein translation. Recently, we have shown that TF-induced
      mature neovessel formation is ultimately driven by CCL2 expression. However, the
      signaling process induced by TF to promote microvessel formation remains to be
      determined. This study was designed with the objective to investigate the
      mechanisms involved in TF-induced neovessel formation. Here, we have identified
      that Ets-1 expression is a downstream effector of TF signaling. TF-siRNA induced
      a highly significant reduction in Ets-1 expression levels and in Ets-1/DNA
      binding while inducing abrogation of microvessel formation. Activation of Ets-1
      rescued the effect of TF inhibition and restored microvessel formation confirming
      the critical role of Ets-1 in TF-induced angiogenesis. VE-cadherin expression, a
      key regulator of endothelial intercellular junctions, and an Ets-1 target
      molecule was dependent of TF-inhibition. We show that TF signals through ERK1/2
      to activate Ets-1 and induce CCL2 gene expression by binding to its promoter
      region. We conclude that endothelial cell TF signals through ERK1/2 and Ets-1 to
      trigger microvessel formation.

PMID- 22869002
TI  - Delta-like 4 inhibits choroidal neovascularization despite opposing effects on
      vascular endothelium and macrophages.
AB  - Inflammatory neovascularization, such as choroidal neovascularization (CNV),
      occur in the presence of Notch expressing macrophages. DLL4s anti-angiogenic
      effect on endothelial cells (EC) has been widely recognized, but its influence on
      Notch signaling on macrophages and its overall effect in inflammatory
      neovascularization is not well understood. We identified macrophages and ECs as
      the main Notch 1 and Notch 4 expressing cells in CNV. A soluble fraction spanning
      Ser28-Pro525 of the murine extracellular DLL4 domain (sDLL4/28-525) activated the
      Notch pathway, as it induces Notch target genes in macrophages and ECs and
      inhibited EC proliferation and vascular sprouting in aortic rings. In contrast,
      sDLL4/28-525 increased pro-angiogenic VEGF, and IL-1beta expression in
      macrophages responsible for increased vascular sprouting observed in aortic rings
      incubated in conditioned media from sDLL4/28-525 stimulated macrophages. In vivo,
      Dll4(+/-) mice developed significantly more CNV and sDLL4/28-525 injections
      inhibited CNV in Dll4(+/-) CD1 mice. Similarly, sDLL4/28-525 inhibited CNV in
      C57Bl6 and its effect was reversed by a gamma-secretase inhibitor that blocks
      Notch signaling. The inhibition occurred despite increased VEGF, IL-1beta
      expression in infiltrating inflammatory macrophages in sDLL4/28-525 treated mice
      and might be due to direct inhibition of EC proliferation in laser-induced CNV as
      demonstrated by EdU labelling in vivo. In conclusion, Notch activation on
      macrophages and ECs leads to opposing effects in inflammatory neovascularization
      in situations such as CNV.

PMID- 22869001
TI  - The hormonal control of ejaculation.
AB  - Hormones regulate all aspects of male reproduction, from sperm production to
      sexual drive. Although emerging evidence from animal models and small clinical
      studies in humans clearly point to a role for several hormones in controlling the
      ejaculatory process, the exact endocrine mechanisms are unclear. Evidence shows
      that oxytocin is actively involved in regulating orgasm and ejaculation via
      peripheral, central and spinal mechanisms. Associations between delayed and
      premature ejaculation with hypothyroidism and hyperthyroidism, respectively, have
      also been extensively documented. Some models suggest that glucocorticoids are
      involved in the regulation of the ejaculatory reflex, but corresponding data from
      human studies are scant. Oestrogens regulate epididymal motility, whereas
      testosterone can affect the central and peripheral aspects of the ejaculatory
      process. Overall, the data of the endocrine system in regulating the ejaculatory
      reflex suggest that widely available endocrine therapies might be effective in
      treating sexual disorders in these men. Indeed, substantial evidence has
      documented that treatments of thyroid diseases are able to improve some
      ejaculatory difficulties.

PMID- 22869004
TI  - Lipase-catalyzed synthesis of hyperbranched poly-L-lactide in an ionic liquid.
AB  - Hyperbranched poly-L-lactides have been synthesized by eROP in [C4MIM][PF6]
      media. The bis(hydroxymethyl)butyric acid molecule was used as the AB2 core co
      monomer and immobilized lipase B from Candida antarctica as biocatalyst. The
      degree of branching could be controlled by the reaction conditions, with the
      maximum achieved being 0.21. The successful achievement of the hyperbranched
      structure is attributed to the high solvent power of substrates and products in
      the ionic liquid besides sustained lipase activity.

PMID- 22869005
TI  - Stimulus-responsive nanopreparations for tumor targeting.
AB  - Nanopreparations such as liposomes, micelles, polymeric and inorganic
      nanoparticles, and small molecule/nucleic acid/protein conjugates have
      demonstrated various advantages over "naked" therapeutic molecules. These
      nanopreparations can be further engineered with functional moieties to improve
      their performance in terms of circulation longevity, targetability, enhanced
      intracellular penetration, carrier-mediated enhanced visualization, and stimuli
      sensitivity. The idea of application of a stimulus-sensitive drug or imaging
      agent delivery system for tumor targeting is based on the significant
      abnormalities in the tumor microenvironment and its cells, such as an acidic pH,
      altered redox potential, up-regulated proteins and hyperthermia. These internal
      conditions as well as external stimuli, such as magnetic field, ultrasound and
      light, can be used to modify the behavior of the nanopreparations that control
      drug release, improve drug internalization, control the intracellular drug fate
      and even allow for certain physical interactions, resulting in an enhanced tumor
      targeting and antitumor effect. This article provides a critical view of current
      stimulus-sensitive drug delivery strategies and possible future directions in
      tumor targeting with primary focus on the combined use of stimulus-sensitivity
      with other strategies in the same nanopreparation, including multifunctional
      nanopreparations and theranostics.

PMID- 22869007
TI  - Distinctive neural signatures for negative sentences in Hindi: an fMRI study.
AB  - We examined cortical activations using functional magnetic resonance imaging
      (fMRI) technique in skilled native Hindi readers while they performed a 'target
      probe' semantic judgment task on affirmative and negative sentences. Hindi, an
      Indo-Aryan language widely spoken in India, follows subject-object-verb (SOV)
      order canonically but allows free word order. The common cortical regions
      involved in affirmative and negative sentence conditions included bilateral
      inferior frontal gyrus (IFG), left parietal cortex (BA 7/40), left fusiform (BA
      37), bilateral supplementary motor area (SMA) (BA 6), bilateral middle temporal
      gyrus (BA 21), and bilateral occipital area (BA 17/18). While no distinct region
      was activated for affirmative sentences, we observed activations in the region of
      bilateral anterior temporal pole for negative sentence. The behavioral results
      showed no significant mean difference for reaction times (RT) and accuracy
      measures between affirmative and negative sentences. However, the imaging results
      suggest the recruitment of anterior temporal pole in processing of negative
      sentences. Region of interest (ROI) analysis for selected regions showed higher
      signal intensity for negative sentences possibly indicating the associated
      inherent difficulty level of processing, especially when integrating information
      related to negations.

PMID- 22869008
TI  - Strongly visible-light responsive plasmonic shaped AgX:Ag (X = Cl, Br)
      nanoparticles for reduction of CO2 to methanol.
AB  - Plasmonic shaped AgX:Ag (X = Cl, Br) nanoparticles have been synthesized by a
      facile and versatile glycerol-mediated solution route. The as-prepared AgX:Ag
      nanoparticles exhibit regular shapes, i.e., cube-tetrapod-like AgCl:Ag
      nanoparticles and AgBr:Ag nanoplates. Compared with the pristine AgX, AgX:Ag
      nanocomposites display stronger absorption in the visible region due to the
      surface plasmon resonance of silver nanoparticles. The calculation of bandgaps
      and band positions indicates the as-achieved AgX:Ag nanoparticles can be used as
      a class of potential photocatalyst for the reduction of CO(2). For example,
      reduction of CO(2) under visible light irradiation with the assistance of the
      anisotropic AgX:Ag nanoparticles yields as much as 100 MUmol methanol in the
      products. Furthermore, the AgX:Ag nanoparticles can maintain its structure and
      activity after 3 runs of reactions. Therefore, the present route opens an avenue
      to acquire plasmonic photocatalysts for conversion of CO(2) into useful organic
      compounds.

PMID- 22869006
TI  - Modulating microglia activity with PPAR-gamma agonists: a promising therapy for
      Parkinson's disease?
AB  - A dysregulated response of the neuroimmune system is a main contributor to the
      progression of neurodegeneration in Parkinson's disease (PD). Recent findings
      suggest that protracted activating stimuli including alpha-synuclein, drive
      microglia to acquire maladaptive functions and to assume a harmful phenotype that
      prevail over a restorative one. Based on this concept, disease-modifying drugs
      should be aimed at targeting suppression of harmful-activated microglia and the
      associated production of neurotoxic molecules as pro-inflammatory cytokines,
      while sparing or inducing beneficial-activated microglia. In this study, we
      review current evidence in support of the beneficial effect of targeting
      peroxisome-proliferator-activated receptor (PPAR)-gamma to achieve
      neuroprotection in PD. PPAR-gamma agonists as rosiglitazone and pioglitazone are
      currently gaining increasing attention as promising disease-modifying drugs in
      this disorder. Early in vitro studies, followed by studies in in vivo models of
      PD, have provided convincing evidence that these drugs inhibit neuronal
      degeneration likely by selectively targeting the expression of neurotoxic factors
      in reactive microglia. Potential therapeutic application has been corroborated by
      recent report of pioglitazone neuroprotective activity in a non-human primate
      model of PD. All together, preclinical evidence have prompted the translation of
      pioglitazone to a phase II clinical trial in early PD.

PMID- 22869009
TI  - Evaluation of depressive symptoms in patients with coronary artery disease using
      the Montgomery Asberg Depression Rating Scale.
AB  - The aim of this study was to evaluate, in patients with coronary artery disease
      (CAD), factor structure and psychometric properties of the Montgomery Asberg
      Depression Rating Scale (MADRS) to identify patients with current major
      depressive episode (MDE). The construct validity of the MADRS against self-rating
      scales was also evaluated. Consecutive 522 CAD patients at admission to the
      cardiac rehabilitation program were interviewed for the severity of depressive
      symptoms using the MADRS and for current MDE using the structured MINI
      International Neuropsychiatric Interview. Also, all patients completed the
      Hospital Anxiety and Depression Scale and the Beck Depression Inventory-II. The
      MADRS had one-factor structure and high internal consistency (Cronbach's
      coefficient alpha=0.82). Confirmative factor analysis indicated an adequate fit:
      comparative fit index=0.95, normed fit index=0.91, and root mean square error of
      approximation=0.07. At a cut-off value of 10 or higher, the MADRS had good
      psychometric properties for the identification of current MDE (positive
      predictive value=42%, with sensitivity=88% and specificity=85%). There was also a
      moderate to strong correlation of MADRS scores with scores on self-rating
      depression scales. In sum, in CAD patients undergoing rehabilitation, the MADRS
      is a unidimensional instrument with high internal consistency and can be used for
      the identification of depressed CAD patients. The association between MADRS and
      self-rating depression scores is moderate to strong.

PMID- 22869010
TI  - A ring of threonines in the inner vestibule of the pore of CNGA1 channels
      constitutes a binding site for permeating ions.
AB  - Cyclic nucleotide-gated (CNG) channels and K+ channels have a significant
      sequence identity and are thought to share a similar 3D structure. K+ channels
      can accommodate simultaneously two or three permeating ions inside their pore and
      therefore are referred to as multi-ion channels. Also CNGA1 channels are multi
      ion channels, as they exhibit an anomalous mole fraction effect (AMFE) in the
      presence of mixtures of 110 mM Li+ and Cs+ on the cytoplasmic side of the
      membrane. Several observations have identified the ring of Glu363 in the outer
      vestibule of the pore as one of the binding sites within the pore of CNGA1
      channels. In the present work we identify a second binding site in the
      selectivity filter of CNGA1 channels controlling AMFE. Here, we show also that
      Cs+ ions at the intracellular side of the membrane block the entry of Na+ ions.
      This blockage is almost completely removed at high hyperpolarized voltages as
      expected if the Cs+ blocking site is located within the transmembrane electric
      field. Indeed, mutagenesis experiments show that the block is relieved when
      Thr359 and Thr360 at the intracellular entrance of the selectivity filter are
      replaced with an alanine. In T359A mutant channels AMFE in the presence of
      intracellular mixtures of Li+ and Cs+ is still present but is abolished in T360A
      mutant channels. These results suggest that the ring of Thr360 at the
      intracellular entrance of the selectivity filter forms another ion binding site
      in the CNGA1 channel. The two binding sites composed of the rings of Glu363 and
      Thr360 are not independent; in fact they mediate a powerful coupling between
      permeation and gating, a specific aspect of CNG channels.

PMID- 22869011
TI  - Inhibition of micturition reflex by activation of somatic afferents in posterior
      femoral cutaneous nerve.
AB  - This study determined if activation of somatic afferents in posterior femoral
      cutaneous nerve (PFCN) could modulate the micturition reflex recorded under
      isovolumetric conditions in alpha-chloralose anaesthetized cats. PFCN stimulation
      inhibited reflex bladder activity and significantly (P <0.05) increased bladder
      capacity during slow infusion of saline or 0.25% acetic acid (AA). The optimal
      frequency for PFCN stimulation-induced bladder inhibition was between 3 and 10
      Hz, and a minimal stimulation intensity of half of the threshold for inducing
      anal twitching was required. Bilateral pudendal nerve transection eliminated PFCN
      stimulation-induced anal twitching but did not change the stimulation-induced
      bladder inhibition, excluding the involvement of pudendal afferent or efferent
      axons in PFCN afferent inhibition.Mechanical or electrical stimulation on the
      skin surface in the PFCN dermatome also inhibited bladder activity. Prolonged (2
      * 30 min) PFCN stimulation induced a post-stimulation inhibition that persists
      for at least 2 h. This study revealed a new cutaneous-bladder reflex activated by
      PFCN afferents. Although the mechanisms and physiological functions of this
      cutaneous-bladder reflex need to be further studied, our data raise the
      possibility that stimulation of PFCN afferents might be useful clinically for the
      treatment of overactive bladder symptoms.

PMID- 22869012
TI  - Neuronal activity in the isolated mouse spinal cord during spontaneous deletions
      in fictive locomotion: insights into locomotor central pattern generator
      organization.
AB  - We explored the organization of the spinal central pattern generator (CPG) for
      locomotion by analysing the activity of spinal interneurons and motoneurons
      during spontaneous deletions occurring during fictive locomotion in the isolated
      neonatal mouse spinal cord, following earlier work on locomotor deletions in the
      cat. In the isolated mouse spinal cord, most spontaneous deletions were non
      resetting, with rhythmic activity resuming after an integer number of cycles.
      Flexor and extensor deletions showed marked asymmetry: flexor deletions were
      accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor
      bursting was not perturbed during extensor deletions. Rhythmic activity on one
      side of the cord was not perturbed during non-resetting spontaneous deletions on
      the other side, and these deletions could occur with no input from the other side
      of the cord. These results suggest that the locomotor CPG has a two-level
      organization with rhythm-generating (RG) and pattern-forming (PF) networks, in
      which only the flexor RG network is intrinsically rhythmic. To further explore
      the neuronal organization of the CPG, we monitored activity of motoneurons and
      selected identified interneurons during spontaneous non-resetting deletions.
      Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor
      related commissural interneurons continued to fire rhythmically during non
      resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of
      rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic
      drive and firing during ipsilateral motor deletions, while type IIV2a
      interneurons lost rhythmic synaptic input and fell silent during deletions. This
      suggests that the type I neurons are components of the RG, whereas the type II
      neurons are components of the PF network.We propose a computational model of the
      spinal locomotor CPG that reproduces our experimental results. The results may
      provide novel insights into the organization of spinal locomotor networks.

PMID- 22869013
TI  - Deletion of heart-type cytochrome c oxidase subunit 7a1 impairs skeletal muscle
      angiogenesis and oxidative phosphorylation.
AB  - Oxidative metabolism is needed for sustained skeletal muscle function. A key
      component of such metabolism is cytochrome c oxidase, the 13-subunit terminal
      complex of the mitochondrial electron transport chain. We used mice null for one
      of the two isoforms of Cox subunit 7a, heart/skeletal muscle-specific Cox7a1, to
      examine the cellular and functional responses of muscle adaptation in response to
      mitochondrial dysfunction. Specifically we determined if deletion of Cox7a1 would
      (1) limit exercise capacity, and (2) alter genes responsible for skeletal muscle
      capillarity and mitochondrial biogenesis. Sixteen male mice (Cox7a1 null mice, n
      = 8, and littermate controls, n = 8) performed incremental and run-to-exhaustion
      treadmill tests. The hindlimb muscles for both groups were analysed. The results
      indicated that capillary indices were reduced (by 30.7-44.9%) in the Cox7a1 null
      mice relative to controls. In addition, resting ATP levels and Cox specific
      activity were significantly reduced (>60%) in both glycolytic and oxidative
      muscle fibre types despite an increase in a major regulator of mitochondrial
      biogenesis, PGC-1beta. These changes in the skeletal muscle resulted in exercise
      intolerance for the Cox7a1 null mice. Thus, our data indicate that deletion of
      the Cox7a1 isoform results in reduced muscle bioenergetics and hindlimb
      capillarity, helping to explain the observed impairment of muscle structure and
      function.

PMID- 22869015
TI  - Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in
      male rat offspring at weaning.
AB  - Maternal nutritional status affects the future development of offspring. Both
      undernutrition and overnutrition in critical periods of life (gestation or
      lactation) may cause several hormonal changes in the pups and programme obesity
      in the adult offspring. We have shown that hyperleptinaemia during lactation
      results in central leptin resistance, higher adrenal catecholamine secretion,
      hyperthyroidism, and higher blood pressure and heart rate in the adult rats.
      Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast
      milk composition and its impact on leptinaemia, energy metabolism, and adrenal
      and thyroid function of the offspring at weaning. We hypothesised that the
      altered source of fat in the maternal diet even under normal calorie intake would
      disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9%
      fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before
      mating and during pregnancy and lactation. HF mothers presented increased total
      body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the
      end of lactation. In consequence, the breast milk from the HF group had higher
      concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and
      triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body
      weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated
      with lower beta3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The
      offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia
      (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found
      lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the
      arcuate nucleus, suggesting leptin resistance. HF offspring also had higher
      adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P <
      0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that
      a high fat diet increases maternal body fat and this additional energy is
      transferred to the offspring during lactation, since at weaning the dams had
      normal fat and the pups were obese. The higher fat and protein concentrations in
      the breast milk seemed to induce early overnutrition in the HF offspring. In
      addition to storing energy as fat, the HF offspring had a larger reserve of
      glycogen and hyperglycaemia that may have resulted from increased
      gluconeogenesis. Hyperleptinaemia may stimulate both adrenal medullary and
      thyroid function, which may contribute to the development of cardiovascular
      diseases. These early changes induced by the maternal high-fat diet may
      contribute to development of metabolic syndrome.

PMID- 22869017
TI  - Photoredox functionalization of C-H bonds adjacent to a nitrogen atom.
AB  - The functionalization of C-H bonds and the visible light photoredox catalysis
      represent two prominent challenges in organic chemistry. In this regard, the
      combination of visible-light catalysis and C-H bond functionalization adjacent to
      a tertiary amine has been successfully developed in the past three years. In this
      tutorial review, we aim to give a brief overview of this issue and state the main
      results obtained in the reactions.

PMID- 22869014
TI  - The pharmacology of neuroplasticity induced by non-invasive brain stimulation:
      building models for the clinical use of CNS active drugs.
AB  - The term neuroplasticity encompasses structural and functional modifications of
      neuronal connectivity. Abnormal neuroplasticity is involved in various
      neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's
      disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke.
      Drugs affecting neuroplasticity are increasingly used as therapeutics in these
      conditions. Neuroplasticity was first discovered and explored in animal
      experimentation. However, non-invasive brain stimulation (NIBS) has enabled
      researchers recently to induce and study similar processes in the intact human
      brain. Plasticity induced by NIBS can be modulated by pharmacological
      interventions, targeting ion channels, or neurotransmitters. Importantly,
      abnormalities of plasticity as studied by NIBS are directly related to clinical
      symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is
      the hypothesis that NIBS-induced plasticity can explore and potentially predict
      the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We
      will (a) review the basics of neuroplasticity, as explored in animal
      experimentation, and relate these to our knowledge about neuroplasticity induced
      in humans by NIBS techniques. We will then (b) discuss pharmacological modulation
      of plasticity in animals and humans. Finally, we will (c) review abnormalities of
      plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS
      with pharmacological intervention may improve our understanding of the
      pathophysiology of abnormal plasticity in these diseases and their purposeful
      pharmacological treatment.

PMID- 22869016
TI  - Tumor suppression by p53 without apoptosis and senescence: conundrum or rapalog
      like gerosuppression?
AB  - I discuss a very obscure activity of p53, namely suppression of senescence
      (gerosuppression), which is also manifested as anti-hypertrophic, anti
      hypermetabolic, anti-inflammatory and anti-secretory effects of p53. But can
      gerossuppression suppress tumors?

PMID- 22869018
TI  - Postoperative cognitive dysfunction is correlated with urine formaldehyde in
      elderly noncardiac surgical patients.
AB  - Post-operative cognitive dysfunction (POCD), especially in elderly patients, has
      been reported in many studies. Although increasing age, duration of anesthesia,
      postoperative infections, and respiratory complications were regarded as the risk
      factors for POCD, no extracerebral diagnostic biomarkers have been identified as
      indicators of POCD. Ninety-five patients, ages 65-80 years, scheduled for major
      orthopedic or abdominal surgery were enrolled. Twenty-two patients aged between
      20 and 40 years undergoing the same procedures served as controls. Subjects
      received neuropsychological tests one-day prior and one week post procedure. To
      determine the presence of POCD, the criteria were used as described in most
      previous studies. Morning urine samples were obtained one day before surgery and
      on day 1, day 2 and day 7 post operatively. Urine formaldehyde was determined
      with high-performance liquid chromatography. The urine formaldehyde level of all
      patients with and without POCD increased on the first 2 days after surgery. But
      the formaldehyde concentration (on day 7) in patients with POCD was significantly
      higher than that in patients without POCD (p < 0.01). In the young control group,
      no patient was diagnosed with POCD. Although the changes in urine formaldehyde of
      young patients during perioperative period were similar to those in elderly
      patients without POCD, the formaldehyde concentrations measured at four time
      points were all significantly lower than those in elderly patients (p < 0.05).
      Levels of urine formaldehyde were elevated in the perioperative period, with the
      highest levels at day 7 in patients with POCD. This suggests that the increase on
      day 7 may provide a new physiologic marker along with neuropsychological
      assessments to assist in the diagnosis of POCD.

PMID- 22869020
TI  - Does unilateral utricular dysfunction cause horizontal spontaneous nystagmus?
AB  - The presence of spontaneous nystagmus in darkness with a strong horizontal
      component has been taken to indicate that there is asymmetrical function of the
      horizontal semicircular canals. If this horizontal spontaneous nystagmus can be
      suppressed by vision, then it is regarded as due to peripheral horizontal canal
      dysfunction.  However, we report evidence from one patient (61-year-old male),
      who visited the MSA ENT Clinic, Cassino (FR) Italy, reporting acute, severe
      vertigo, postural unsteadiness, nausea and vomiting associated with right sudden
      hearing loss. The patient received instrumental audiovestibular testing to obtain
      objective measurements of his inner-ear receptors. At the time of the attack, the
      patient showed spontaneous nystagmus, mainly with horizontal and vertical
      components (3D infrared video-oculography). Video head-impulse tests of dynamic
      horizontal canal function showed that the functional status of both horizontal
      canals was within the normal range. Cervical VEMPs to 500 Hz bone-conducted
      vibration at Fz showed normal results; ocular VEMPs to the same stimulus showed a
      reduced n10 amplitude beneath the left eye, corresponding to the right ear. For
      this reason, the patient was diagnosed as having right unilateral selective
      utricular macula lesion due to labyrinthitis. There is considerable evidence of
      convergence of neural input from the otoliths onto horizontal canal neurons in
      the vestibular nuclei. The firing of such neurons could reflect either
      asymmetrical horizontal canal function or asymmetrical utricular function. The
      problem with this patient was not due to asymmetrical horizontal canal function,
      but only to asymmetrical utricular function, demonstrated by the results of the
      oVEMP test.

PMID- 22869019
TI  - Geniposide reduces inflammatory responses of oxygen-glucose deprived rat
      microglial cells via inhibition of the TLR4 signaling pathway.
AB  - Geniposide, an iridoid glycoside isolated from Gardenia, has neuroprotective
      activities against oxidative stress and inflammation. The present study
      investigated the in vivo protective effect of geniposide on ischemia/reperfusion
      injured rats by middle cerebral artery occlusion (MCAO), and the inhibitory
      effects of geniposide and mechanisms against activation of microglial cells by
      oxygen-glucose deprivation (OGD) in vitro. Male SD rats were subjected to
      treatment with geniposide at 15, 30 and 60 mg/kg immediately after MCAO. Cerebral
      infarct volume and microglial cell activation were assessed following 24 h
      reperfusion. Cultured primary rat microglial cells were exposed to geniposide at
      the concentrations of 12.5, 25 and 50 MUg/mL during 4 h of OGD. The effects of
      geniposide were evaluated in terms of (1) cell viability; (2) secretion of TNF
      alpha, IL-1beta, IL-6, IL-8 and IL-10 into culture media; (3) TLR4 mRNA
      expression; (4) protein expression of TLR4, p-ERK1/2, p-IkappaB, p-p38, nuclear
      and cytoplasmic fraction NF-kappaB p65; and (5) nuclear transfer of NF-kappaB
      p65. Geniposide reduced the infarct volume and inhibited the activation of
      microglial cells in ischemic penumbra in vivo. OGD increased cell viability and
      release of TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10, these effects were
      suppressed by geniposide. Geniposide also attenuated the increases in the OGD
      induced TLR4 mRNA and protein levels. In addition, geniposide at 25 and 50 MUg/mL
      downregulated the phosphorylation of ERK, IkappaB and p38, as well as inhibited
      nuclear transcriptional activity triggered via NF-kappaB p65 in microglial cells
      by OGD. In conclusion, geniposide displays a neuroprotective effect on
      ischemia/reperfusion-injured rats in vivo and inhibits OGD-induced activation of
      microglial cells by attenuating inflammatory factors and NF-kappaB activation in
      vitro.

PMID- 22869021
TI  - Multidisciplinary difficult airway simulation training: two year evaluation and
      validation of a novel training approach at a District General Hospital based in
      the UK.
AB  - Our objective was to devise and assess a multidisciplinary simulated course in
      training junior doctors for possible difficult airway scenarios. The authors have
      run a multi-disciplinary difficult airway simulation that was designed to
      simulate the stresses and complications of a live situation. The course comprised
      of six to eight difficult airway simulations (using a Laerdal SimMan2 mannequin
      remote controlled by a "driver") with two teams moving through the simulations
      over half a day. The simulation lasted 20 min and was followed by 40 min of in
      depth structured facilitated debrief. The course was set in the anaesthetic room
      of a district general hospital theatre. Seventy-eight candidates (28 anaesthetic
      trainees, 18 ENT trainees, 19 theatre nurses and 13 operating theatre
      practitioners) attended this course over 6 training days set over 2 years. The
      main outcome measures of candidate feedback scored for eight questions on a 1-6
      Likert scale. From the results, Audit of Trust inpatient airway fatalities
      revealed three deaths in 2 years leading up to the introduction of the simulation
      course. Re-audit of the subsequent 2 years, during which time the course was
      running, has shown no airway fatalities. A 100 % candidate feedback response rate
      was obtained. Delegates gave an average score of 4.8 to the simulator replicating
      the stress of 'live' situations; 5.5 to the simulator addressing training needs;
      5.6 to the course improving clinical knowledge, teamwork, leadership and non
      technical skills. In our conclusions, successful management of a difficult airway
      situation requires rapid evaluation, effective communication, strong leadership
      and teamwork, as well as knowledge of local environment and equipment. The
      results show that candidates felt an improvement in clinical knowledge, teamwork,
      leadership and non-technical skills, as well as the mutual understanding and
      respect between related medical and non-medical team members. In addition, audit
      of airway mortality showed a Trust-wide reduction in inpatient airway related
      mortality following the course. The results emphatically demonstrate the
      universal success of this multi-disciplinary training method for all team
      members, regardless of hierarchical position or background.

PMID- 22869022
TI  - Macular and peripapillary choroidal thickness in diabetic patients.
AB  - PURPOSE: To investigate macular and peripapillary choroidal thickness (CT) in
      diabetic patients with and without diabetic retinopathy (DR). METHODS: One
      hundred and fifty subjects were enrolled: 102 diabetic patients (102 eyes) and 48
      normals, as controls. Exclusion criteria were previously treated DR, refractive
      error higher than +/- 3 diopters, and treated or untreated glaucoma. All patients
      underwent full ophthalmic examination, stereoscopic color fundus photography, and
      spectral domain optical coherence tomography (RS-3000; Nidek). Spectral domain
      optical coherence tomography examination consisted of linear scans, 6 mm in
      length, centered onto the fovea, and circle scan positioned around the optic disk
      (3.46 mm in diameter). Choroidal thickness was measured manually at the fovea and
      at 1, 2, and 3 mm distance along all scans in the macula. Peripapillary CT was
      measured at eight points along the circle scan. All measurements were performed
      independently by 2 masked graders. RESULTS: Mean age was not significantly
      different between patients with diabetes and controls. In the macular area, CT
      was significantly lower in the nasal quadrant versus all other quadrants (P <
      0.0001), in both groups. In the peripapillary area, CT was significantly lower in
      the inferior quadrant versus all other quadrants (P < 0.05), in both groups. Mean
      macular and peripapillary CT progressively and significantly decreased with
      increasing level of DR (nonproliferative and proliferative DR vs. controls, P <
      0.05). No significant CT difference was found between controls and diabetic eyes
      without detectable DR. Diabetic macular edema did not influence CT. Interobserver
      coefficient of repeatability was 28.8 (95% confidence interval, 24.8-32.8) for
      foveal measurements and 13.0 (95% confidence interval, 11.2-14.8) for
      peripapillary measurements. Pearson correlation coefficient was 0.99, and P
      <0.0001 for all measurements. CONCLUSION: Choroidal thickness is reduced in
      diabetic eyes and parallels appearance and evolution of DR. Spectral domain
      optical coherence tomography clearly confirms in vivo previously reported
      histopathologic observations. The role of choroid in the pathophysiology of DR
      needs to be adequately investigated.

PMID- 22869023
TI  - Surgical repair of macular fold after vitrectomy for bullous rhegmatogenous
      retinal detachment.

PMID- 22869024
TI  - Skin protection using Tegaderm in the postoperative eye patient.

PMID- 22869025
TI  - Diagnostic and therapeutic challenges.

PMID- 22869026
TI  - Evidence of recurrent microvascular occlusions associated with acute branch
      retinal artery occlusion demonstrated with spectral-domain optical coherence
      tomography.

PMID- 22869028
TI  - Peripheral retinal vascular leakage demonstrated by ultra-widefield fluorescein
      angiography in preeclampsia with HELLP syndrome.

PMID- 22869027
TI  - Exercise-induced acute changes in systolic blood pressure do not alter choroidal
      thickness as measured by a portable spectral-domain optical coherence tomography
      device.
AB  - PURPOSE: To measure choroidal thickness in patients manifesting an acute change
      in systemic arterial blood pressure using a portable spectral-domain optical
      coherence tomography device (iVue). METHODS: Fifteen patients (15 eyes)
      undergoing cardiac exercise stress testing were scanned using a portable spectral
      domain optical coherence tomography system (iVue). Two scan protocols were used:
      cross line scan for measuring choroidal thickness and the retina map scan to
      measure retinal thickness. Each patient was scanned before and within 3 minutes
      after the stress test. Blood pressure was measured at the same time as the
      acquisition of the scans. Choroidal thickness was measured from the posterior
      edge of the retinal pigment epithelium to the choroid-sclera junction at 500-MUm
      intervals up to 1,000 MUm temporal and nasal to the fovea. Retinal thickness was
      measured by an automated software. All choroidal thickness measurements were
      performed by two independent observers. RESULTS: Fifteen patients (15 eyes) with
      a mean age of 60.6 (+/-10.4 years) were scanned. There was a significant increase
      in systolic but not diastolic pressure after stress testing (P < 0.05). The mean
      choroidal thickness measurements showed no significant difference before and
      after exercise stress testing (P > 0.05). In addition, there was no significant
      difference in retinal thickness before and after stress testing measurements (P >
      0.05). CONCLUSION: There was no change in choroidal thickness or retinal
      thickness, despite an acute change in the systemic systolic blood pressure
      induced by exercise.

PMID- 22869030
TI  - TOMM40 association with Alzheimer disease: tales of APOE and linkage
      disequilibrium.

PMID- 22869031
TI  - Latrepirdine stimulates autophagy and reduces accumulation of alpha-synuclein in
      cells and in mouse brain.
AB  - Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated
      with enhanced cognition, neuroprotection and neurogenesis in laboratory animals,
      and has entered phase II clinical trials for both Alzheimer's disease and
      Huntington's disease (HD). Based on recent indications that latrepirdine protects
      cells against cytotoxicity associated with expression of aggregatable
      neurodegeneration-related proteins, including Abeta42 and gamma-synuclein, we
      sought to determine whether latrepirdine offers protection to Saccharomyces
      cerevisiae. We utilized separate and parallel expression in yeast of several
      neurodegeneration-related proteins, including alpha-synuclein (alpha-syn), the
      amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD
      associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene;
      htt-103Q). Latrepirdine effects on alpha-syn clearance and toxicity were also
      measured following treatment of SH-SY5Y cells or chronic treatment of wild-type
      mice. Latrepirdine only protected yeast against the cytotoxicity associated with
      alpha-syn, and this appeared to occur via induction of autophagy. We further
      report that latrepirdine stimulated the degradation of alpha-syn in
      differentiated SH-SY5Y neurons, and in mouse brain following chronic
      administration, in parallel with elevation of the levels of markers of autophagic
      activity. Ongoing experiments will determine the utility of latrepirdine to
      abrogate alpha-syn accumulation in transgenic mouse models of alpha-syn
      neuropathology. We propose that latrepirdine may represent a novel scaffold for
      discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might
      yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy
      body dementia, rapid eye movement (REM) sleep disorder and/or multiple system
      atrophy, following optimization of its pro-autophagic and pro-neurogenic
      activities. 

PMID- 22869032
TI  - Association of DISC1 variants with age of onset in a population-based sample of
      recurrent major depression.

PMID- 22869033
TI  - Why has it taken so long for biological psychiatry to develop clinical tests and
      what to do about it?
AB  - Patients with mental disorders show many biological abnormalities which
      distinguish them from normal volunteers; however, few of these have led to tests
      with clinical utility. Several reasons contribute to this delay: lack of a
      biological 'gold standard' definition of psychiatric illnesses; a profusion of
      statistically significant, but minimally differentiating, biological findings;
      'approximate replications' of these findings in a way that neither confirms nor
      refutes them; and a focus on comparing prototypical patients to healthy controls
      which generates differentiations with limited clinical applicability. Overcoming
      these hurdles will require a new approach. Rather than seek biomedical tests that
      can 'diagnose' DSM-defined disorders, the field should focus on identifying
      biologically homogenous subtypes that cut across phenotypic diagnosis--thereby
      sidestepping the issue of a gold standard. To ensure clinical relevance and
      applicability, the field needs to focus on clinically meaningful differences
      between relevant clinical populations, rather than hypothesis-rejection versus
      normal controls. Validating these new biomarker-defined subtypes will require
      longitudinal studies with standardized measures which can be shared and compared
      across studies--thereby overcoming the problem of significance chasing and
      approximate replications. Such biological tests, and the subtypes they define,
      will provide a natural basis for a 'stratified psychiatry' that will improve
      clinical outcomes across conventional diagnostic boundaries.

PMID- 22869035
TI  - A genome-wide association study of post-traumatic stress disorder identifies the
      retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus.
AB  - We describe the results of the first genome-wide association study (GWAS) of post
      traumatic stress disorder (PTSD) performed using trauma-exposed white non
      Hispanic participants from a cohort of veterans and their intimate partners (295
      cases and 196 controls). Several single-nucleotide polymorphisms (SNPs) yielded
      evidence of association. One SNP (rs8042149), located in the retinoid-related
      orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally
      significant associations were observed for other RORA SNPs in two African
      American replication samples-one from the veteran cohort (43 cases and 41
      controls) and another independent cohort (100 cases and 421 controls). However,
      only the associated SNP from the veteran African-American replication sample
      survived gene-level multiple-testing correction. RORA has been implicated in
      prior GWAS studies of psychiatric disorders and is known to have an important
      role in neuroprotection and other behaviorally relevant processes. This study
      represents an important step toward identifying the genetic underpinnings of
      PTSD. 

PMID- 22869036
TI  - Comparative RNA editing in autistic and neurotypical cerebella.
AB  - Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated
      epigenetic modification shown to modulate complex behavior in animals. Little is
      known about human A-to-I editing, but it is thought to constitute one of many
      molecular mechanisms connecting environmental stimuli and behavioral outputs.
      Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed
      light on gene-environment interactions underlying complex behavior in health and
      disease. Synaptic function is a main target of A-to-I editing, which can
      selectively recode key amino acids in synaptic genes, directly altering synaptic
      strength and duration in response to environmental signals. Here, we performed a
      high-resolution survey of synaptic A-to-I RNA editing in a human population, and
      examined how it varies in autism, a neurodevelopmental disorder in which synaptic
      abnormalities are a common finding. Using ultra-deep (>1000 * ) sequencing, we
      quantified the levels of A-to-I editing of 10 synaptic genes in postmortem
      cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range
      of editing levels was detected across individuals and editing sites, from 99.6%
      to below detection limits. In most sites, the extreme ends of the population
      editing distributions were individuals with autism. Editing was correlated with
      isoform usage, clusters of correlated sites were identified, and differential
      editing patterns examined. Finally, a dysfunctional form of the editing enzyme
      adenosine deaminase acting on RNA B1 was found more commonly in postmortem
      cerebella from individuals with autism. These results provide a population-level,
      high-resolution view of A-to-I RNA editing in human cerebella and suggest that A
      to-I editing of synaptic genes may be informative for assessing the epigenetic
      risk for autism. 

PMID- 22869037
TI  - Striatal dopamine release in schizophrenia comorbid with substance dependence.
AB  - Dopamine (DA) has a role in the pathophysiology of schizophrenia and addiction.
      Imaging studies have indicated that striatal DA release is increased in
      schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted
      in addiction, mostly in the ventral striatum (VST). Therefore, we aimed to
      measure striatal DA release in patients with comorbid schizophrenia and substance
      dependence. We used [(11)C]raclopride positron emission tomography and an
      amphetamine challenge to measure baseline DA D2-receptor availability (BPND) and
      its percent change post-amphetamine (DeltaBPND, to index amphetamine-induced DA
      release) in striatal subregions in 11 unmedicated, drug-free patients with both
      schizophrenia and substance dependence, and 15 healthy controls. There were no
      significant group differences in baseline BPND. Linear mixed modeling using
      DeltaBPND as the dependent variable and striatal region of interest as a repeated
      measure indicated a significant main effect of diagnosis, F(1,24)=8.38, P=0.008,
      with significantly smaller DeltaBPND in patients in all striatal subregions (all
      P <= 0.04) except VST. Among patients, change in positive symptoms after
      amphetamine was significantly associated with DeltaBPND in the preDCA (rs=0.69,
      P=0.03) and VST (rs=0.64, P=0.05). In conclusion, patients with comorbid
      schizophrenia and substance dependence showed significant blunting of striatal DA
      release, in contrast to what has been found in schizophrenia without substance
      dependence. Despite this blunting, DA release was associated with the transient
      amphetamine-induced positive-symptom change, as observed in schizophrenia. This
      is the first description of a group of patients with schizophrenia who display
      low presynaptic DA release, yet show a psychotic reaction to increases in D2
      stimulation, suggesting abnormal postsynaptic D2 function.

PMID- 22869038
TI  - Increased inflammatory markers identified in the dorsolateral prefrontal cortex
      of individuals with schizophrenia.
AB  - Upregulation of the immune response may be involved in the pathogenesis of
      schizophrenia with changes occurring in both peripheral blood and brain tissue.
      To date, microarray technology has provided a limited view of specific
      inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used
      SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels
      in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and
      their matched controls. We detected 798 differentially regulated transcripts
      present in people with schizophrenia compared with controls. Ingenuity pathway
      analysis identified the inflammatory response as a key change. Using quantitative
      real-time PCR we confirmed the changes in candidate cytokines and immune
      modulators, including interleukin (IL)-6, IL-8, IL-1beta and SERPINA3. The
      density of major histocompatibility complex-II-positive cells morphologically
      resembling microglia was significantly increased in schizophrenia and correlated
      with IL-1beta expression. A group of individuals, most of whom had schizophrenia,
      were found to have increased inflammatory mRNA expression. In summary, we have
      demonstrated changes in an inflammatory response pathway that are present in ~40%
      of people diagnosed with schizophrenia. This suggests that therapies aimed at
      immune system attenuation in schizophrenia may be of direct benefit in the brain.

PMID- 22869040
TI  - Visual evoked potentials in patients with pineal gland cyst.
AB  - AIMS: The functional effect of the pineal gland cyst is difficult to evaluate
      with visual field examination. The aim of this study is to investigate the
      usefulness of visual evoked potentials (VEP) in patients with pineal gland cyst
      due to the possible compression on the visual pathway. SUBJECTS AND METHODS:
      Black-and-white pattern-reversal checkerboard VEP were recorded in 75 patients
      (50 females and 25 males, mean age 26.3 +/- 15.7 and 25.6 +/- 17.6 years,
      respectively) with pineal gland cyst detected on magnetic resonance of the brain
      (subject group) and 75 age and sex-matched control subjects (control group).
      Amplitudes and P100 latencies were collected and later grouped as: (1) normal
      finding; (2) prechiasmal; (3) prechiasmal and postchiasmal; and (4) postchiasmal
      dysfunction. RESULTS: P100 latencies differed significantly between subject
      (110.26 +/- 13.23 ms) and control group (101.01 +/- 5.36 ms) (p < 0.01). Findings
      of the VEP differed significantly (p < 0.01) between subject and control group,
      mainly due to the postchiasmal dysfunction frequency in subject group. Findings
      of the VEP differed significantly according to the pineal gland cyst volume (p =
      0.006) with more frequent postchiasmal dysfunctions among subjects with larger
      cysts. Postchiasmal changes were significantly more frequent in patients with
      described compression of the cyst on surrounding brain structures (p = 0.016).
      CONCLUSIONS: Postchiasmal dysfunction on VEP can be seen in patients with pineal
      gland cyst, mostly with larger cysts and with compression of the cyst on
      surrounding brain structures. VEP serve as a useful method to determine
      functional impairment of the visual pathway in patients with pineal gland cyst.

PMID- 22869042
TI  - NDRG4, the N-Myc downstream regulated gene, is important for cell survival, tumor
      invasion and angiogenesis in meningiomas.
AB  - Meningiomas are the second most common brain tumor, and 20-30% of these tumors
      are aggressive. The aggressive subtypes are characterized by a capacity for
      invasion of normal brain with frequent and destructive recurrence patterns.
      Effective local therapies include surgery and radiation, but there is a need for
      novel molecular targets to improve survival and reduce morbidity for this group
      or cancer patients. We have recently identified the N-Myc downstream regulated
      gene 4, NDRG4, protein as being overexpressed in aggressive meningioma, and in
      this report, demonstrate its role in cell survival, invasion/migration and
      angiogenesis. Downregulation of NDRG4 mRNA and protein expression in two high
      grade meningioma cancer cell lines, IOMM-Lee and CH-157 MN resulted in reduction
      in cell survival, DNA fragmentation and G2-M cell cycle arrest. NDRG4
      downregulation also decreased cellular invasion and migration, as determined by
      spheroid migration, linear and radial wound healing, Boyden chamber matrigel
      invasion, and 3D invasion assays. To determine the effect of NDRG4 depletion on
      angiogenesis, we studied the immortalized brain endothelial cell line, bEnd.3. We
      treated bEnd.3 cells with conditioned media from NDRG4-depleted IOMM-Lee and CH
      157 MN cells and abrogated their ability to elicit bEnd.3 capillary-like tubes,
      to proliferate, and to invade. NDRG4 is not overexpressed in bEnd.3 cells and
      direct NDRG4 depletion had no effect on the cells. This study is significant as
      it is the first to demonstrate the functional role of NDRG4 in various aspects of
      meningioma tumor biology. NDRG4 is involved in modulating cell proliferation,
      invasion, migration and angiogenesis in meningioma, and may play a valuable role
      as a molecular target in its treatment.

PMID- 22869041
TI  - Metabolic, hormonal and immunological associations with global DNA methylation
      among postmenopausal women.
AB  - DNA methylation is an epigenetic modification essential for the regulation of
      gene expression that has been implicated in many diseases, including cancer. Few
      studies have investigated the wide range of potential predictors of global DNA
      methylation, including biomarkers. Here, we investigated associations between DNA
      methylation and dietary factors, sex-steroid hormones, metabolic, lipid,
      inflammation, immune and one-carbon biomarkers. Data and baseline biomarker
      measurements were obtained from 173 overweight/obese postmenopausal women. Global
      DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for
      LINE-1 repeats. We used correlations and linear regression analyses to
      investigate associations between continuous data and DNA methylation, while t
      tests were used for categorical data. Secondary analyses stratified by serum
      folate levels and multivitamin use were also conducted. There was little
      variability in LINE-1 methylation (66.3-79.5%). Mean LINE-1 methylation was
      significantly higher among women with elevated glucose levels. Mean LINE-1
      methylation was also higher among women with high CD4+/CD8+ ratio, and lower
      among women with elevated vitamin B6, but neither reached statistical
      significance. In analyses stratified by folate status, DNA methylation was
      negatively associated with sex hormone concentrations (estrone, estradiol,
      testosterone and sex hormone binding globulin) among women with low serum folate
      levels (n = 53). Conversely, among women with high serum folate levels (n = 53),
      DNA methylation was positively associated with several immune markers (CD4/CD8
      ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that
      global DNA methylation is generally stable, with differential associations for
      sex hormones and immune markers depending on one-carbon status.

PMID- 22869043
TI  - Prevention of intracranial in-stent restenoses: predilatation with a drug eluting
      balloon, followed by the deployment of a self-expanding stent.
AB  - PURPOSE: Stenting in intracranial atherosclerotic disease (ICAD) is increasingly
      debated, due to issues of procedural safety, technical efficacy, and in-stent
      recurrent stenoses (ISR). In the present study, feasibility, safety, and efficacy
      of angioplasty using a drug-eluting balloon (DEB) followed by the implantation of
      a self-expanding stent (Enterprise) were evaluated for the treatment of ICAD
      lesions. METHODS: Fifty-two patients (median age: 71 years; range: 54-86 years;
      male/female ratio 37:15) underwent stenting of high-grade ICAD lesions between
      February 2010 and November 2011 in a single center. Angioplasty using a
      paclitaxel coated SeQuent Please (B. Braun, Germany) or DIOR (Eurocor, Germany)
      coronary PTCA balloon, followed by the implantation of a self-expanding stent
      (Enterprise, Codman, USA) was performed in 54 lesions. Angiographic and clinical
      follow-up was performed at 6 and 12 weeks, 6 and 12 months, and yearly
      thereafter. Technical success rate, periprocedural complications, occurrence of
      recurrent ischemic symptoms, and the development of an ISR were analyzed.
      RESULTS: Angioplasty using a DEB followed by stent implantation was successfully
      performed in 44 (81 %) cases. DEB insertion failed in 19 % of the cases and
      angioplasty was finally performed using a conventional PTCA balloon. The combined
      procedure related permanent neurologic morbidity and mortality rate (stroke, ICH,
      and subarachnoid hemorrhage) at 30 days and beyond was 5 %. Angiographic and
      clinical follow-up were obtained in 33 (61 %) lesions in 32 patients. Recurrent
      stenosis was seen in one (3 %) lesion. CONCLUSION: Angioplasty and stenting using
      a DEB is safe and yields encouragingly low ISR rates. Further technical
      developments to improve lesion accessibility are, nevertheless, mandatory.

PMID- 22869039
TI  - Structure and function of biotin-dependent carboxylases.
AB  - Biotin-dependent carboxylases include acetyl-CoA carboxylase (ACC), propionyl-CoA
      carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC), geranyl-CoA
      carboxylase, pyruvate carboxylase (PC), and urea carboxylase (UC). They contain
      biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier
      protein components. These enzymes are widely distributed in nature and have
      important functions in fatty acid metabolism, amino acid metabolism, carbohydrate
      metabolism, polyketide biosynthesis, urea utilization, and other cellular
      processes. ACCs are also attractive targets for drug discovery against type 2
      diabetes, obesity, cancer, microbial infections, and other diseases, and the
      plastid ACC of grasses is the target of action of three classes of commercial
      herbicides. Deficiencies in the activities of PCC, MCC, or PC are linked to
      serious diseases in humans. Our understanding of these enzymes has been greatly
      enhanced over the past few years by the crystal structures of the holoenzymes of
      PCC, MCC, PC, and UC. The structures reveal unanticipated features in the
      architectures of the holoenzymes, including the presence of previously
      unrecognized domains, and provide a molecular basis for understanding their
      catalytic mechanism as well as the large collection of disease-causing mutations
      in PCC, MCC, and PC. This review will summarize the recent advances in our
      knowledge on the structure and function of these important metabolic enzymes.

PMID- 22869044
TI  - Insertion of balloon retained gastrostomy buttons: a 5-year retrospective review
      of 260 patients.
AB  - PURPOSE: Radiologically inserted gastrostomy (RIG) is an established way of
      maintaining enteral nutrition in patients who cannot maintain nutrition orally.
      The purpose of this study was to evaluate the safety and efficacy of primary
      placement of a wide bore button gastrostomy in a large, varied patient population
      through retrospective review. METHODS: All patients who underwent gastrostomy
      placement from January 1, 2004 to January 1, 2009 were identified. 18-Fr
      gastrostomy buttons (MIC-Key G) were inserted in the majority. Follow-up ranged
      from 6 months to 4.5 years. RESULTS: A total of 260 patients (M:F 140:120,
      average age 59.2 years) underwent gastrostomy during the study period. Overall
      success rate for RIG placement was 99.6 %, with success rate of 95.3 % for
      primary button insertion. Indications included neurological disorders (70 %),
      esophageal/head and neck malignancy (21 %), and other indications (9 %). Major
      and minor complication rates were 1.2 and 12.8 %, respectively. Thirty-day
      mortality rate was 6.8 %. One third of patients underwent gastrostomy reinsertion
      during the study period, the main indication for which was inadvertent catheter
      removal. Patency rate was high at 99.5 %. The maximum number of procedures in any
      patient was 8 (n = 2), and the average tube dwell time was 125 days. CONCLUSIONS:
      Primary radiological insertion of a wide bore button gastrostomy is a safe
      technique, with high success rate, high patency rate, and low major complication
      rate. We believe that it is feasible to attempt button gastrostomy placement in
      all patients, once tract length is within limits of tube length. If difficulty is
      encountered, then a standard tube may simply be placed instead.

PMID- 22869045
TI  - Posterior circulation stroke after bronchial artery embolization. A rare but
      serious complication.
AB  - Bronchial artery embolization (BAE) is the treatment of choice for massive
      hemoptysis with rare complications that generally are mild and transient. There
      are few references in the medical literature with acute cerebral embolization as
      a complication of BAE. We report a case of intracranial posterior territory
      infarctions as a complication BAE in a patient with hemoptysis due to
      bronchiectasis.

PMID- 22869046
TI  - Changes in hepatic blood flow during transcatheter arterial infusion with heated
      saline in hepatic VX2 tumor.
AB  - PURPOSE: This study evaluates the influence of transcatheter arterial infusion
      with heated saline on hepatic arterial and portal venous blood flows to tumor and
      normal hepatic tissues in a rabbit VX2 tumor model. METHODS: All animal
      experiments were approved by the institutional animal care and use committee.
      Twenty rabbits with VX2 liver tumors were divided into the following two groups:
      (a) the treated group (n = 10), which received a 60 mL transarterial injection of
      60  degrees C saline via the hepatic artery; (b) the control group (n = 10),
      which received a 60 mL injection of 37  degrees C saline via the hepatic artery.
      Using ultrasonography, the blood flows in both the portal vein and hepatic artery
      were measured, and the changes in the hemodynamic indices were recorded before
      and immediately after the injection. The changes in the tumor and normal liver
      tissues of the two groups were histopathologically examined by hematoxylin and
      eosin staining after the injection. RESULTS: After the transcatheter arterial
      heated infusion, there was a decrease in the hepatic arterial blood flow to the
      tumor tissue, a significant decrease in the hepatic artery mean velocity (P <
      0.05), and a significant increase in the resistance index (P < 0.05). On
      hematoxylin and eosin staining, there were no obvious signs of tissue destruction
      in the normal liver tissue or the tumor tissue after heated perfusion, and
      coagulated blood plasma was observed in the cavities of intratumoral blood
      vessels in the treated group. CONCLUSIONS: The changes in tumor blood flow in the
      rabbit VX2 tumor model were presumably caused by microthrombi in the tumor
      vessels, and the portal vein likely mediated the heat loss in normal liver tissue
      during the transarterial heated infusion.

PMID- 22869047
TI  - Factors influencing medical student attrition and their implications in a large
      multi-center randomized education trial.
AB  - Participant attrition may be a significant threat to the generalizability of the
      results of educational research studies if participants who do not persist in a
      study differ from those who do in ways that can affect the experimental outcomes.
      A multi-center trial of the efficacy of different computer-based instructional
      strategies gave us the opportunity to observe institutional and student factors
      linked to attrition from a study and the ways in which they altered the
      participation profile. The data is from a randomized controlled trial conducted
      at seven US medical schools investigating the educational impact of different
      instructional designs for computer-based learning modules for surgical clerks.
      All students undertaking their surgical clerkships at the participating schools
      were invited participate and those that consented were asked to complete five
      study measures during their surgery clerkship. Variations in study attrition
      rates were explored by institution and by participants' self-regulation, self
      efficacy, perception of task value, and mastery goal orientation measured on
      entry to the study. Of the 1,363 invited participants 995 (73 %) consented to
      participate and provided baseline data. There was a significant drop in the rate
      of participation at each of the five study milestones with 902 (94 %) completing
      at least one of two module post-test, 799 (61 %) both module post-tests, 539 (36
      %) the mid-rotation evaluation and 252 (25 %) the final evaluation. Attrition
      varied between institutions on survival analysis (p < 0.001). Small but
      statistically significant differences in self-regulation (p = 0.01), self
      efficacy (p = 0.02) and task value (p = 0.04) were observed but not in mastery or
      performance goal orientation measures (p = NS). Study attrition was correlated
      with lower achievement on the National Board of Medical Examiners subject exam.
      The results of education trials should be interpreted with the understanding that
      students who persist may be somewhat more self-regulated, self-efficacious and
      higher achievers than their peers who drop out and as such do not represent the
      class as a whole. 

PMID- 22869048
TI  - Increased morbidity in acute viral hepatitis with glucose-6-phosphate
      dehydrogenase deficiency.

PMID- 22869049
TI  - Achalasia cardia.

PMID- 22869051
TI  - NEDD9, a novel target of miR-145, increases the invasiveness of glioblastoma.
AB  - miR-145 is an important repressor of pluripotency in embryonic stem cells and a
      tumor suppressor in different cancers. Here, we found that miR-145 is strongly
      down-regulated in glioblastoma (GB) specimens and corresponding
      glioblastomaneurospheres (GB-NS, containing GB stem-like cells) compared to
      normal brain (NB) and to low-grade gliomas (LGG). We observed a direct
      correlation between miR-145 expression and the progression-free survival (PFS) in
      LGG patients and overall survival (OS) in GB patients. Using microarray analysis,
      we identified relevant differences in gene expression profiles between GB-NS over
      expressing miR-145 (miRover-NS) and GB-NS Empty (Empty-NS). We focused our
      attention on HEF1/Cas-L/NEDD9, a scaffold protein involved in invasion in several
      types of cancer. We confirmed a significant down-regulation of NEDD9 in miRover
      NS and we found a higher expression in GB and GB-NS compared to NB. Approximately
      50% of LGG patients expressed higher levels of NEDD9 than NB, and the PFS of such
      patients was shorter than in patients expressing lower levels of NEDD9. We
      observed that intracranial injection of GB-NS over-expressing miR-145 delays
      significantly tumor development :deriving tumors showed a significant down
      regulation of NEDD9. In addition, we demonstrated a significant inhibition of
      invasion in silencing experiments with GB-NS shNEDD9 (shNEDD9), and an up
      regulation of miR-145 in shNEDD9, suggesting a doublenegative feedback loop
      between miR-145 and NEDD9. Our results demonstrate the critical role of miR-145
      and NEDD9 in regulating glioblastoma invasion and suggest a potential role of
      NEDD9 as a biomarker for glioma progression.

PMID- 22869052
TI  - Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in
      tumorigenesis.
AB  - PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating
      cellular responses to hormones and cytokines. Against original prediction as
      tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a
      proto-oncogene because activating mutations of this gene are associated with
      leukemogenesis. However, most recent experimental data suggest PTPN11/Shp2 acting
      as a tumor suppressor in hepatocarcinogenesis. This review focuses on the tumor
      promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.

PMID- 22869053
TI  - Assessing the social impact of cancer: a review of available tools.
AB  - OBJECTIVES: Taking care of oncological patients holistically--from a biological,
      social, and psychological point of view--also involves evaluating the social
      aspects of the disease. In the present study, we provide further insights on how
      investigations regarding the social impact of an oncological disease are
      conducted with specifically designed tools on patients who have personally been
      affected. The objective is then to understand how the social dimension is
      theorized and, therefore, which practical aspects of subjective experience are
      employed to assess the social impact. METHOD: We performed a systematic review of
      the literature identified by MedLine and PsycINFO databases. RESULTS: Of the 469
      articles obtained from the search, 27 deal with 14 different measurement
      instruments of the social impact of the oncological experience. Of the identified
      tools, 71% were specifically designed for the oncological setting and were
      heterogeneous both in the investigated domains as well as social referrals; 64%
      of these had a multidimensional structure. Internal consistency was reported for
      all instruments, while temporal stability only for 36% of the tools. Construct
      validity and concurrent validity were reported for 79% of the instruments,
      criterion and predictive validity for one instrument only, external validity for
      18% of the tools, and cross-cultural validity for one instrument only. The
      content was directly available for most instruments. CONCLUSIONS: The great
      interest in this subject as borne out by the amount of studies published in
      international psycho-oncological literature confirms the importance of having a
      valid and reliable instrument specifically dedicated to measuring the social
      impact of the oncological experience. At the same time, further investigation is
      required to investigate the psychometric properties of the existing tools.

PMID- 22869054
TI  - Palonosetron plus single-dose dexamethasone for the prevention of nausea and
      vomiting in women receiving anthracycline/cyclophosphamide-containing
      chemotherapy: meta-analysis of individual patient data examining the effect of
      age on outcome in two phase III trials.
AB  - PURPOSE: Data from two randomized trials, evaluating a single-day regimen of
      palonosetron plus dexamethasone against emesis due to moderately emetogenic
      chemotherapy, were assessed for the impact of age on outcome in a pooled sample
      of women receiving anthracycline and/or cyclophosphamide (AC)-containing
      chemotherapy. METHODS: Chemo-naive breast cancer patients randomized to receive
      palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n =
      200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3
      (n = 205), were included in the analysis. The primary endpoint was complete
      response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period.
      The effect of the 1-day regimen and age (<50 and >= 50 years) was investigated by
      a meta-analysis of individual patient data. RESULTS: Younger patients comprised
      43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the
      pooled sample received the AC combination. There were no between-treatment
      differences in CR rate according to age during all observation periods. In the 1
      day regimen group, 55.2 % of younger patients achieved overall CR compared with
      54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients
      achieved overall CR compared with 58.7 % of older patients. In the adjusted
      analysis, younger age was not associated with overall CR to treatment (risk
      difference, -3.1 %; 95 % CI, -13.0 to 6.7 %; P = 0.533). CONCLUSIONS: These
      results provide evidence that, irrespective of age, the dexamethasone-sparing
      regimen is not associated with a significant loss in overall anti-emetic
      protection in women undergoing AC-containing chemotherapy.

PMID- 22869056
TI  - Salinity and temperature tolerance of brown-marbled grouper Epinephelus
      fuscoguttatus.
AB  - Grouper have to face varied environmental stressors as a result of drastic
      changes to water conditions during the storm season. We aimed to test the
      response of brown-marbled grouper to drastic and gradual changes in temperature
      and salinity to understand the grouper's basic stress response. The results can
      improve the culture of grouper. Brown-marbled grouper, Epinephelus fuscoguttatus
      (6.2 +/- 0.8 g) were examined for temperature and salinity tolerances at nine
      different environmental regimes (10, 20, and 33 0/00 combined with 20, 26 and 32 
      degrees C), in which the fish were subjected to both gradual and sudden changes
      in temperature and salinity. The critical thermal maximum (50 % CTMAX) and the
      upper incipient lethal temperature (UILT) were in the ranges of 35.9-38.3 and
      32.7-36.5  degrees C, respectively. The critical thermal minimum (50 % CTMIN) and
      the lower incipient lethal temperature (LILT) were in the ranges of 9.8-12.2 and
      14.9-22.3  degrees C, respectively. The critical salinity maximum (50 % CSMAX)
      and the upper incipient lethal salinity (UILS) were in the ranges of 67.0-75.5
      and 54.2-64.8 0/00, respectively. Fish at temperature of 20  degrees C and a
      salinity of 33 0/00 tolerated temperatures as low as 10  degrees C when the
      temperature was gradually decreased. Fish acclimated at salinities of 10-33 0/00
      and a temperature of 32  degrees C tolerated salinities of as high as 75-79 0/00.
      All fish survived from accumulating salinity after acute transfer to 20, 10, 5,
      and 3 0/00. But all fish died while transferred to 0 0/00. Relationships among
      the UILT, LILT, 50 % CTMAX, 50 % CTMIN, UILS, 50 % CSMAX, salinity, and
      temperature were examined. The grouper's temperature and salinity tolerance
      elevated by increasing acclimation temperature and salinity. On the contrary, the
      grouper's temperature and salinity tolerance degraded by decreasing acclimation
      temperature and salinity. The tolerance of temperature and salinity on grouper in
      gradual changes were higher than in drastic changes.

PMID- 22869055
TI  - Late preterm birth: a review of medical and neuropsychological childhood
      outcomes.
AB  - Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly
      three-fourths of all preterm births, making this population a sizeable public
      health concern. The immature fetal development associated with LP delivery
      increases the risk of mortality and short-term medical complications. Which
      combination of maternal, fetal, or neonatal risk factors may be most critical has
      only recently begun to be addressed, and whether LP birth's disruptive impact on
      brain development will exert adverse effects on neuropsychological functioning in
      childhood and adolescence has been understudied. Early data have shown a graded
      response, with LP children often functioning better than very preterm children
      but worse than term children, and with subtle intellectual and neuropsychological
      deficits in LP children compared with healthy children born at term gestational
      age. Further characterization of the neuropsychological profile is required and
      would be best accomplished through prospective longitudinal studies. Moreover,
      since moderate and LP births result in disparate medical and psychological
      outcomes, the common methodology of combining these participants into a single
      research cohort to assess risk and outcome should be reconsidered. The rapidly
      growing LP outcomes literature reinforces a critical principle: fetal development
      occurs along a dynamic maturational continuum from conception to birth, with each
      successive gestational day likely to improve overall outcome.

PMID- 22869057
TI  - Dynamic biomechanical examination of the lumbar spine with implanted total disc
      replacement using a pendulum testing system.
AB  - STUDY DESIGN: Biomechanical cadaver investigation. OBJECTIVE: To examine dynamic
      bending stiffness and energy absorption of the lumbar spine with and without
      implanted total disc replacement (TDR) under simulated physiological motion.
      SUMMARY OF BACKGROUND DATA: The pendulum testing system is capable of applying
      physiological compressive loads without constraining motion of functional spinal
      units (FSUs). The number of cycles to equilibrium observed under pendulum testing
      is a measure of the energy absorbed by the FSU. METHODS: Five unembalmed, frozen
      human lumbar FSUs were tested on the pendulum system with axial compressive loads
      of 181 N, 282 N, 385 N, and 488 N before and after Synthes ProDisc-L TDR
      implantation. Testing in flexion, extension, and lateral bending began by
      rotating the pendulum to 5o resulting in unconstrained oscillatory motion. The
      number of rotations to equilibrium was recorded and bending stiffness (N.m/o) was
      calculated and compared for each testing mode. RESULTS: In flexion/extension, the
      TDR constructs reached equilibrium with significantly (P < 0.05) fewer cycles
      than the intact FSU with compressive loads of 282 N, 385 N, and 488 N. Mean
      dynamic bending stiffness in flexion, extension, and lateral bending increased
      significantly with increasing load for both the intact FSU and TDR constructs (P
      < 0.001). In flexion, with increasing compressive loading from 181 N to 488 N,
      the bending stiffness of the intact FSUs increased from 4.0 N.m/o to 5.5 N.m/o,
      compared with 2.1 N.m/o to 3.6 N.m/o after TDR implantation. At each compressive
      load, the intact FSU was significantly stiffer than the TDR (P < 0.05).
      CONCLUSION: Lumbar FSUs with implanted TDR were found to be less stiff, but
      absorbed more energy during cyclic loading with an unconstrained pendulum system.
      Although the effects on clinical performance of motion-preserving devices are not
      fully known, these results provide further insight into the biomechanical
      behavior of these devices under approximated physiological loading conditions.

PMID- 22869059
TI  - The pressure distribution of cerebrospinal fluid responds to residual compression
      and decompression in an animal model of acute spinal cord injury.
AB  - STUDY DESIGN: In vivo large animal (pig) model study of cerebrospinal fluid (CSF)
      pressures after acute experimental spinal cord injury (SCI). OBJECTIVE: To
      determine how the CSF pressure (CSFP) and CSF pulse pressure amplitude (CSFPPA)
      cranial and caudal to the injury site change after an acute SCI with subsequent
      thecal occlusion and decompression. SUMMARY OF BACKGROUND DATA: Lowering
      intrathecal pressure via CSF drainage is currently instituted to prevent ischemia
      induced SCI during thoracoabdominal aortic aneurysm surgery and was recently
      investigated as a potential intervention for acute traumatic SCI. However, in SCI
      patients, persistent extradural compression commonly occludes the subarachnoid
      space. This may generate a CSFP differential across the injury site, which cannot
      be appreciated with lumbar catheter pressure measurements. METHODS: Anesthetized
      pigs were subjected to an acute contusive SCI at T11 and 8 hours of sustained
      compression (n = 12), or sham surgery (n = 2). CSFP was measured cranial and
      caudal to the injury site, using miniature pressure transducers, during
      compression and for 6 hours after decompression. RESULTS: The cranial-caudal CSFP
      differential increased (mean, 0.39 mm Hg/h), predominantly due to increased
      cranial pressure. On decompression, cranial CSFP decreased (mean, -1.16 mm Hg)
      and caudal CSFP increased (mean, 0.65 mm Hg). The CSFP differential did not
      change significantly after decompression. Cranial CSFPPA was greater than caudal
      CSFPPA, but this differential did not change during compression. On
      decompression, the caudal CSFPPA increased in some but not all animals.
      CONCLUSION: Although extradural compression exists at the site of injury, lumbar
      CSFP may not accurately indicate CSFP cranial to the injury. Decompression may
      provide immediate, though perhaps partial, resolution of the pressure
      differential. CSFPPA was not a consistent indicator of decompression in this
      animal model. These findings may have implications for the design of future
      clinical protocols in which CSFP is monitored after acute SCI.

PMID- 22869060
TI  - Correlation of vertebral strength topography with 3-dimensional computed
      tomographic structure.
AB  - STUDY DESIGN: Biomechanical and radiographical study. OBJECTIVE: To test the
      hypothesis that stiffness and strength at discrete sites of human lumbar
      vertebrae depend on the 3-dimentional structure and density of the vertebral-body
      bone elements, and can be evaluated using models based on vertebral bone
      characteristics obtained from quantitative computed tomogrphy. SUMMARY OF
      BACKGROUND DATA: We have not found published methods that allow in vivo
      evaluation of bone mechanical properties at discrete sites of vertebral body
      applicable for clinical use.We hypothesize that human lumbar vertebral strength
      topography depends on the local 3-dimensional structural features of the bone
      structure, and that the stiffness and strength can be evaluated at discrete sites
      using models based on data obtained from quantitative computed tomographic (CT)
      images. METHODS: Forty-eight vertebrae (8 L1, 8 L2, 8 L3, 10 L4, and 14 L5) from
      14 cadaveric subjects (9 men and 5 women; age, 43-99 yr) were studied. Stiffness
      (modulus of elasticity) and strength (maximum load and maximum tolerable
      pressure) were defined by an indentation test at 11 discrete sites on the cranial
      and caudal surfaces of each vertebral endplate. Before the indentation test
      radiography, dual-energy x-ray absorptiometry, micro-CT, and conventional-CT (con
      CT) of the vertebrae were performed. Micro-CT characteristics of cortical and
      cancellous bones of 18 vertebrae were measured at each region of interest defined
      by a 3-dimensional coordinate system. The most informative indices regarding
      endplate strength were selected by correlation analysis. Predictive models of
      local stiffness and strength were created using selected indices obtained by
      micro-CT and con-CT (40 vertebrae) images. RESULTS: Local stiffness and strength
      of the tested specimens were highly variable. Endplate thickness and density in
      combination with adjacent trabecular bone density, existence of endplate defects,
      and subject's age were good predictors of local stiffness and strength,
      applicable for con-CT. Polynomial multiple regression of these characteristics
      provides the best correlation with stiffness (r2 = 0.82; P < 0.001) and strength
      (r2 = 0.74). CONCLUSION: Stiffness and strength at discrete sites of human lumbar
      vertebrae depend on the superficial vertebral bone structure and density and can
      be evaluated using models based on quantitative analysis of micro-CT and con-CT
      images.

PMID- 22869061
TI  - Mortality and morbidity in early-onset scoliosis surgery.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To accurately determine
      complication rates, particularly mortality rates, in surgically treated early
      onset scoliosis. SUMMARY OF BACKGROUND DATA: The advent of modern segmental
      instrumentation for spinal fusion surgery in adolescent scoliosis has allowed for
      application of similar nonsegmental unfused techniques aimed at controlling
      scoliosis in the very young child. The dismal prognosis for these children
      without repeated spinal lengthening procedures is unquestioned, although no
      controlled trials exist. Many, if not most, of these children need surgery;
      however, the surgical complication rate is very high. METHODS: During the study
      period, all surgically treated children with early-onset scoliosis seen at our
      institution were identified. Any patient who presented to our clinic with early
      onset scoliosis that was surgically managed was included. The total number of
      procedures, type of implants, number and type of complications, geographic origin
      of the cases, and final outcomes were all assessed. RESULTS: A total of 165
      surgical procedures on 28 patients accrued during the study time period,
      including index implantation of instrumentation, lengthening, and definitive
      fusion, as well as operations performed for complications such as wound
      debridement and revision of failed implants. Clinical diagnoses included
      congenital scoliosis, syndromic and chromosomal abnormalities, cerebral palsy,
      and spinal muscular atrophy. There was a complication rate of 84% overall with a
      mortality rate of almost 18%. The only patients with no complications were those
      whose entire surgical course had been at our institution only. The mortality rate
      was equal in patients whose treatment was performed elsewhere versus exclusively
      in our center. CONCLUSION: This study underlines the grave severity of these
      scolioses particularly in syndromic children. The high mortality rate is
      alarming, suggesting that further study is needed in this area.

PMID- 22869062
TI  - Surgical treatment of Lenke 1 main thoracic idiopathic scoliosis: results of a
      prospective, multicenter study.
AB  - STUDY DESIGN: Prospective, consecutive, nonrandomized, multicenter study.
      OBJECTIVE: The purpose of this study was to compare the outcomes of idiopathic
      scoliosis treatment for Lenke 1 curves with 3 treatment approaches. SUMMARY OF
      BACKGROUND DATA: Surgical treatment options for Lenke 1 or primary main thoracic
      curve pattern in adolescent idiopathic scoliosis include thoracoscopic anterior
      spinal fusion, open anterior spinal fusion, and posterior spinal fusion (PSF) and
      instrumentation procedures. METHODS: This was a prospective, consecutive,
      nonrandomized, multicenter study of surgical correction in adolescent idiopathic
      scoliosis. Patients with Lenke type 1 curve patterns from 7 sites were enrolled
      in this minimum 2-year follow-up study. Changes in pre- to postoperative
      radiographs, pulmonary function tests, Scoliosis Research Society questionnaire
      scores, and trunk rotation measures were compared. RESULTS: A total of 149
      patients (age: 14.5 +/- 2 yr) were included (91% follow-up at 2 yr). The 3 groups
      were similar preoperatively in thoracic and lumbar curve size. There were 55
      patients with thoracoscopic anterior spinal fusion, 17 patients with open
      anterior spinal fusion, and 64 patients with PSF. The fusion included on average
      3 to 4 more levels in PSF than the 2 anterior approaches (P <= 0.001). Surgical
      time tended to be greater in the anterior groups by approximately 2 to 3 hours;
      however, blood loss was greatest with PSF. At 2 years, all 3 approaches showed
      similar improvements in the thoracic Cobb angle, coronal balance, the lumbar Cobb
      angle, Scoliosis Research Society questionnaire scores, and trunk rotation
      measures. The PSF approach resulted in overall reduction in kyphosis compared
      with the anterior approaches. Postoperative hyperkyphosis was an issue only in
      the 2 anterior groups. Major complication rates were similar. CONCLUSION: All 3
      approaches resulted in similarly satisfactory outcomes for the majority of
      patients with specific advantages to each technique. The patients with PSF had
      more levels fused, yet with the shortest operative time. The thoracoscopic
      anterior spinal fusion group had the smallest incisions and the lowest
      requirement for transfusion. The open anterior spinal fusion group had a modest
      loss of pulmonary function without any clear advantages compared with the other 2
      groups. LEVEL OF EVIDENCE: 2.

PMID- 22869063
TI  - Comparison of 3 reconstructive techniques in the surgical management of
      multilevel cervical spondylotic myelopathy.
AB  - STUDY DESIGN: A retrospective comparative study was performed in patients with 3
      level cervical spondylotic myelopathy (CSM). OBJECTIVE: To compare the clinical
      outcomes, radiological parameters, and complication incidence of 3 reconstructive
      techniques after the anterior decompression of multilevel CSM. SUMMARY OF
      BACKGROUND DATA: There has been growing interest in combination of anterior
      cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion
      (ACCF) for the treatment of multilevel CSM in recent years. However, the clinical
      efficacy and radiological outcomes of the hybrid decompression and fusion (HDF)
      have rarely been investigated. METHODS: A total of 180 consecutive patients with
      3-level CSM undergoing the anterior decompression and fusion procedures from
      January 2003 to July 2010 were retrospectively investigated. According to various
      reconstructive techniques, the patients were divided into 3 groups: HDF, ACDF,
      and ACCF groups. The clinical effects and improvements of cervical and segmental
      lordosis in each group were assessed. In addition, the fusion rate, postoperative
      complications, and radiographical adjacent-level changes regarding each group
      were also evaluated. RESULTS: No statistical differences in clinical effects,
      restoration of cervical lordosis, and incidences of postoperative complications
      were found between the HDF and ACDF groups (P > 0.05). The ACCF group has
      achieved clinical effects similar to the ACDF or HDF group (P > 0.05), but it had
      more bleeding, lower fusion rate, and higher incidences of postoperative
      complications compared with the ACDF or HDF group (P < 0.05). The improvements of
      the cervical and segmental lordosis in the ACCF group were significantly less
      than the ACDF or HDF group (P < 0.05). There was no significant difference in
      radiographical adjacent-level changes among the 3 groups (P > 0.05). CONCLUSION:
      The HDF can be considered an effective and safe alternative procedure compared
      with ACDF in the treatment of the multilevel CSM, and ACCF should be the last
      option.

PMID- 22869066
TI  - Identification  of hybrids between triticale and Aegilops juvenalis (Thell.) Eig
      and  determination of genetic similarity with ISSRs.
AB  - Wide  hybridization expands the gene pool of cultivated species and can produce 
      genotypes with practical value, often resistant to diseases. In plants, ISSRs 
      are often used for hybrid identification as well as for diversity evaluation.  We
      estimated genetic similarity among advanced genetic stocks of triticale  hybrids
      and identified Aegilops juvenalis introgressions into triticale.  Fourteen ISSR
      primers amplified from 12 to 23 DNA fragments. The number of  polymorphic
      products per primer ranged from three to nine, with a mean of 5.1.  The
      polymorphic information content values ranged from 0.39 to 0.66, with a  mean of
      0.52. Thirteen primers amplified products indicating presence of A.  juvenalis
      chromatin. The largest mean genetic similarity (0.84) with all  other forms was
      shown by a strain derived from an A. juvenalis 6x *  [(Lanca * L506/79) *
      CZR142/79] hybrid, while A. juvenalis was the least  similar (0.33). We conclude
      that ISSRs can reliably identify A. juvenalis chromatin  in the triticale
      background and efficiently estimate genetic similarity of  hybrids and parental
      forms.

PMID- 22869067
TI  - Association of the CD36 gene  with impaired glucose tolerance, impaired fasting
      glucose, type-2 diabetes, and  lipid metabolism in  essential hypertensive
      patients.
AB  - Essential  hypertension is a common disorder that can increase the risk of type 2
      diabetes  (T2D). CD36 has been studied in patients with diabetes and hypertension
      extensively; however, few studies have focused on the relationship of the CD36
      gene with impaired fasting glucose (IFG)/impaired glucose tolerance (IGT)  or T2D
      in essential hypertension patients. To identify rs1049673 and rs1527483 in the
      CD36 gene conferring susceptibility to IFG/IGT and T2D, we  conducted a case
      control study in 1257 essential hypertension patients among  the Han Chinese
      population (control: 676; IGT/IFG: 468; T2D: 113). We also  evaluated the impact
      of two loci on insulin sensitivity, glucose tolerance and  serum lipid. The major
      findings of this study were that rs1049673 was  found associated with IFG/IGT and
      T2D in essential hypertension patients (Pco  = 0.028; Pdom = 0.015). The
      rs1049673 G carriers showed  significant higher Glu0 (betadom =  0.08
      (0.01~0.16), Pdom = 0.045) and Lp(a) (betaco = 0.04  (0.002~0.07), Pco = 0.041;
      betadom = 0.06 (0.01~0.12), Pdom = 0.032), and  lower HDL by the linear
      regression with the adjustment for gender, age, BMI,  and mean blood pressures.
      These findings provided evidence that the CD36 gene  may play some role in the
      pathogenesis of IFG/IGT and T2D in essential  hypertension patients.

PMID- 22869068
TI  - Cloning and  sequencing of the rDNA gene family of the water buffalo (Bubalus
      bubalis).
AB  - The  rDNA genes coding for ribosomal RNA in animals are complicated repeat
      sequences  with high GC content. We amplified water buffalo rDNA gene sequences
      with the  long and accurate (LA) PCR method, using LA Taq DNA polymerase and GC
      buffer,  based on bioinformatic analysis of related organisms. The rDNA genes
      were found  to consist of 9016 nucleotides, including three rRNA genes and two
      internal  transcribed spacers (ITS), which we named 18S rRNA, ITS1, 5.8S rRNA,
      ITS2 and  28S rRNA. We tested and optimized conditions for cloning these
      complicated rDNA  sequences, including specific rules of primer design,
      improvements in the  reaction system, and selection of the DNA polymerase.

PMID- 22869069
TI  - Identification of markers tightly linked to tomato  yellow leaf curl disease and
      root-knot nematode resistance by multiplex PCR.
AB  - Seven different commercial F1 hybrids and two F2 populations were evaluated by
      multiplex PCR to identify plants that are homozygous or heterozygous for Ty-1 and
      Mi, which confer resistance to tomato yellow leaf curl disease and root-knot
      nematode, respectively. The Ty-1 and Mi markers were amplified by PCR and
      identified by digestion of the amplicons with the TaqI enzyme. The hybrids E13
      and 288 were found to be Ty/ty heterozygous plants with 398-, 303-, and 95-bp
      bands, and B08, 314, 198, and A10 were found to be ty/ty homozygous plants with a
      398-bp band; whereas 098 did not give any PCR products. The hybrids E13 and 198
      were found to be Mi/Mi homozygous plants with 570- and 180-bp bands, and 288 and
      A10 were found to be Mi/mi heterozygous plants, with 750-, 570- and 180-bp bands,
      and B08, 109 and 314 were found to be mi/mi homozygous plants with only a 750-bp
      band. We additionally developed a multiplex PCR technique for JB-1 and Mi, which
      confer resistance to tomato yellow leaf curl disease and root-knot nematode. The
      JB-1 marker identified the genotype of the Ty gene, and the plants that produced
      the 400-bp band were ty/ty homozygous plants, whereas the plants that produced
      400- and 500-bp bands were resistant to tomato yellow leaf curl disease. We
      conclude that multiplex PCRs can be used to reproducibly and efficiently detect
      these resistance genes.

PMID- 22869065
TI  - Effects of growth hormone-releasing hormone on cognitive function in adults with
      mild cognitive impairment and healthy older adults: results of a controlled
      trial.
AB  - BACKGROUND: Growth hormone-releasing hormone(GHRH), growth hormone, and insulin
      like growth factor 1 have potent effects on brain function, their levels decrease
      with advancing age, and they likely play a role in the pathogenesis of Alzheimer
      disease. Previously, we reported favorable cognitive effects of short-term GHRH
      administration in healthy older adults and provided preliminary evidence to
      suggest a similar benefit in adults with mild cognitive impairment (MCI).
      OBJECTIVE: To examine the effects of GHRH on cognitive function in healthy older
      adults and in adults with MCI. DESIGN: Randomized,double-blind,placebo-controlled
      trial. SETTING: Clinical Research Center, University of Washington School of
      Medicine in Seattle. PARTICIPANTS: A total of 152 adults (66 with MCI) ranging in
      age from 55 to 87 years (mean age, 68 years); 137 adults (76 healthy participants
      and 61 participants with MCI) successfully completed the study. INTERVENTION:
      Participants self-administered daily subcutaneous injections of tesamorelin
      (Theratechnologies Inc),a stabilized analog of human GHRH (1 mg/d), or placebo 30
      minutes before bedtime for 20 weeks. At baseline, at weeks 10 and 20 of
      treatment, and after a 10-week washout(week 30), blood samples were collected,
      and parallel versions of a cognitive battery were administered. Before and after
      the 20-week intervention, participants completed an oral glucose tolerance test
      and a dual-energy x-ray absorptiometry scan to measure body composition. MAIN
      OUTCOME MEASURES: Primary cognitive outcomes were analyzed using analysis of
      variance and included 3 composites reflecting executive function, verbal memory,
      and visual memory. Executive function was assessed with Stroop Color-Word
      Interference,Task Switching, the Self-Ordered Pointing Test, and Word Fluency,
      verbal memory was assessed with Story Recall and the Hopkins Verbal Learning
      Test,and visual memory was assessed with the Visual-Spatial Learning Test and
      Delayed Match-to-Sample. RESULTS: The intent-to-treat analysis indicated a
      favorable effect of GHRH on cognition (P=.03), which was comparable in adults
      with MCI and healthy older adults.The completer analysis showed a similar
      pattern, with a more robust GHRH effect (P=.002). Subsequent analyses indicated a
      positive GHRH effect on executive function (P=.005) and a trend showing a similar
      treatment-related benefit in verbal memory(P=.08). Treatment with GHRH increased
      insulin like growth factor 1 levels by 117 %(P.001), which remained within the
      physiological range, and reduced percent body fat by 7.4%(P.001). Treatment with
      GHRH increased fasting insulin levels within the normal range by 35%in adults
      with MCI (P.001) but not in healthy adults. Adverse events were mild and were
      reported by 68%of GHRH treated adults and 36% of those who received placebo.
      CONCLUSIONS: Twenty weeks of GHRH administration had favorable effects on
      cognition in both adults with MCI and healthy older adults. Longer-duration
      treatment trials are needed to further examine the therapeutic potential of GHRH
      administration on brain health during normal aging and "pathological aging."
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00257712

PMID- 22869070
TI  - Doxycycline-regulated  growth hormone gene expression system for swine.
AB  - Although  growth hormone gene transgenic animals are much larger than normal
      animals,  they manifest differences that have adverse effects on survival due to 
      overexpression of growth hormone. We developed a stable pig embryonic  fibroblast
      cell line expressing pig growth hormone (pGH) using the Tet-On  system, with
      which we can conditionally manipulate expression of pGH in vivo.  Inducible
      expression of pGH was achieved by combining reserve Tet-controlled 
      transcriptional activator and tetracycline-responsive element in a single 
      plasmid. The mRNA expression of pGH was significantly increased compared to the 
      non-induced group by about 10-fold. The controlled secretion of pGH induced by 
      doxycycline was further tested in stably transfected cells. We conclude that 
      inducible GH expression can be achieved in pig embryonic fibroblasts.

PMID- 22869071
TI  - A novel NF1 mutation  in a Chinese patient with giant cafe-au-lait macule in
      neurofibromatosis type 1  associated with a malignant peripheral nerve sheath
      tumor and bone abnormality.
AB  - Neurofibromatosis  type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder
      that is  characterized by multiple cafe-au-lait, skinfold freckling, Lisch
      nodules, and  neurofibromas. Mutations in the NF1 gene, which encodes the 
      neurofibromin protein, have been identified as  the pathogenic gene of NF1. In
      this study, we present a clinical and molecular  study of a Chinese patient with
      giant cafe-au-lait in NF1. The patient showed  >6 cafe-au-lait spots on the body,
      axillary freckling, and multiple  subcutaneous neurofibromas. He also had a
      malignant  peripheral nerve sheath tumor and bone abnormalities. The germline
      mutational  analysis of the NF1 gene revealed a novel missense mutation in exon
      13.  It is a novel heterozygous nucleotide G>A transition at position 2241 of the
      NF1 gene. We found no mutation in malignant peripheral nerve sheath  tumor DNA
      from this patient. This expands the database for NF1 gene  mutations in NF1. Its
      absence in the normal chromosomes suggests that it is  responsible for the NF1
      phenotype. To our knowledge, this is the first  case of giant cafe-au-lait macule
      in NF1 associated with a malignant peripheral  nerve sheath tumor and bone
      abnormality.

PMID- 22869072
TI  - Mapping of HtNB,  a gene conferring non-lesion resistance before heading to
      Exserohilum  turcicum (Pass.), in a maize inbred line derived from the Indonesian
      variety Bramadi.
AB  - The gene HtNB confers non-lesion resistance to the fungal pathogen Exserohilum
      turcicum in maize. To map this gene, we developed two F2 populations, P111
      (resistant line) x HuangZao 4 (susceptible line) and P111 x B73 (susceptible).
      HtNB was located on chromosome 8.07 bin, flanked by MAC216826-4 and umc2218 at
      distances of 3.3 and 3.4 cM, respectively. HtNB appears to be a new gene
      responsible for resistance to northern corn leaf blight. Functions of the genes
      in the region between umc1384 and umc2218 were predicted. In addition, several
      genes were found to be related to disease resistance, such as the genes encoding
      Ser/Thr protein kinase and protein-like leaf senescence.

PMID- 22869073
TI  - Nine polymorphic STR loci in the HLA region in the Shaanxi Han population of
      China.
AB  - A large number of microsatellite genetic markers have  been identified in the
      human leukocyte antigen (HLA) region. We investigated  genetic polymorphism of
      the nine short tandem repeat (STR) loci (D6S276, MOGCA,  D6S265, MIB, D6S273,
      G51152, TAP1CA, RING3CA, and D6S291) in the HLA region in  the Shaanxi Han
      population. Using a fluorescence-labeled multiplex-PCR STR  typing method, 6-13
      alleles were detected in these nine STR loci in 150  unrelated Han Chinese from
      the region of Shaanxi, China. The distributions of  the genotypes at these nine
      loci were in Hardy-Weinberg equilibrium. We  conclude that these nine STR loci
      have a high level of genetic polymorphism;  they would be useful for population
      genetic studies, pre-transplantation HLA  typing, forensic and paternity testing,
      etc.

PMID- 22869074
TI  - Association of neuropeptide Y and gonadotrophin-releasing hormone receptor gene
      SNPs  with breeding value for growth and egg production traits in Mazandaran
      native chickens.
AB  - Neuropeptide  Y (NPY) and gonadotrophin-releasing hormone receptor (GnRHR) are
      two candidate  genes with a wide variety of physiological functions in growth and
      especially  in reproduction processes. We examined the association of one SNP
      from each of  these genes with growth- and egg production-related traits in
      Mazandaran native  chickens. Two hundred and six individuals were genotyped by
      PCR-RFLP.  Marker-trait association analyses were performed using both breeding
      value and  phenotypic information. The data came from 18 successive generations
      of  selection at a Mazandaran native chicken breeding station in Iran. Data were 
      analyzed with a univariate animal model in an ASREML procedure to estimate 
      breeding values of the birds for these traits. Two alleles were found for both 
      genes, A and a alleles for GnRHR, with frequencies of 0.614 and 0.386, B and b 
      alleles for NPY, with frequencies of 0.780 and 0.221, respectively. The  additive
      genetic effects of the GnRHR gene on egg number and egg mass were  significant.
      Also, body weight at sexual maturity was significantly influenced  by the NPY
      gene. We conclude that GnRHR and NPY genes are associated with egg  production
      and growth traits, respectively.

PMID- 22869075
TI  - Barcoding the  major Mediterranean leguminous crops by combining universal
      chloroplast and  nuclear DNA sequence targets.
AB  - The  ability to discriminate all species is the ultimate target in barcoding. The
      Mediterranean basin is a center of origin for legumes and thus they have played 
      a key role in feeding the Mediterranean population. It is also a region with 
      important protected designation of origin and protected geographical indication 
      legumes that provide income in rural areas. We evaluated the use of two
      chloroplast  regions, trnL and rpoC1, and a nuclear internal transcriber  region,
      ITS2, for their efficiency to barcode the main Mediterranean leguminous  crops.
      Twenty-five legume species were studied. Plant material of pasture and  legumes
      was obtained from the Greek GenBank and the Fodder Crops and Pastures  Institute
      (National Agricultural Research Foundation). DNA was extracted with  the Qiagen
      DNeasy plant mini-kit and PCR amplification was performed using the  Kapa Taq DNA
      polymerase using primers amplifying the chloroplast trnL and rpoC1 regions or the
      nuclear region ITS2. PCR products were sequenced  and the sequences were aligned
      using CLUSTAL W. Species identification based on  the sequence similarity
      approach was performed using the GenBank database. In  order to evaluate
      intraspecific and interspecific divergence in legumes we used  Molecular
      Evolutionary Genetics Analysis 5 and for pairwise Kimura 2-parameter  distance
      calculations for all 3 DNA regions (2 chloroplast regions, trnL and rpoC1, and
      the nuclear region ITS2). Four tree-based methods (neighbor  joining and maximum
      parsimony, maximum likelihood, and Bayesian inference  analyses) were used to
      exhibit the molecular identification results to  represent differences as an
      uprooted dendrogram. Additionally, the sequence  character-based method was used
      with DnaSP and the information from each site  was treated as a character to
      distinguish the species from one another. The DNA  regions trnL and ITS2
      successfully (100%) discriminated the  Mediterranean crop legume species used,
      while rpoC1 identified only 72%  of them. Furthermore, the use of the trnL region
      enabled the  discrimination of even very closely related species, like Phaseolus
      lunatus and P. coccineus or Vicia faba subsp major with V. faba subsp minor,
      which are so closely related that even in NCBI they were both  referred as
      Phaseolus vulgaris and V. faba, respectively. We  conclude that trnL and ITS2 are
      efficient DNA barcoding target regions  in order to discriminate Mediterranean
      leguminous crops and provide a reliable  and efficient tool for the scientific,
      agricultural and industrial community.

PMID- 22869076
TI  - Genetic  diversity of polysporic isolates of Moniliophthora perniciosa
      (Tricholomataceae).
AB  - The  causal agent of witches' broom disease, Moniliophthora perniciosa is a 
      hemibiotrophic and endemic fungus of the Amazon basin and the most important 
      cocoa disease in Brazil. The purpose of this study was to analyze the genetic 
      diversity of polysporic isolates of M. perniciosa to evaluate the  adaptation of
      the pathogen from different Brazilian regions and its association  with different
      hosts. Polysporic isolates obtained previously in potato  dextrose agar cultures
      of M. perniciosa from different Brazilian states  and different hosts (Theobroma
      cacao, Solanum cernuum, S.  paniculatum, S. lycocarpum, Solanum sp, and others)
      were  analyzed by somatic compatibility grouping where the mycelium interactions
      were  distinguished after 4-8 weeks of confrontation between the different
      isolates  of M. perniciosa based on the precipitation line in the transition zone
      and by protein electrophoresis through SDS-PAGE. The diversity of polysporic 
      isolates of M. perniciosa was grouped according to geographic proximity  and
      respective hosts. The great genetic diversity of M. perniciosa strains  from
      different Brazilian states and hosts favored adaptation in unusual  environments
      and dissemination at long distances generating new biotypes.

PMID- 22869077
TI  - Characteristics  of protein variants in trichlorphon-resistant Bactrocera
      dorsalis (Diptera;  Tephritidae) larvae.
AB  - Functional  proteins in larvae of Bactrocera dorsalis, a major fruit pest, play a
      central role in their resistance to organophosphorus insecticides. Changes in 
      proteins in B. dorsalis larvae after trichlorphon treatment may have a  role in
      the resistance response to trichlorphon. We analyzed 14 protein spots  of crude
      proteins from B. dorsalis larvae post-treatment with trichlorphon  in two
      dimensional gel electrophoresis through mass spectrometry and protein 
      sequencing. We found functional proteins that are responsible for signal 
      transduction (pkaap and dual specificity tyrosine-phosphorylation-regulated 
      kinase), immunity (hemolectin), synthesis and decomposition (twinstar,  cathepsin
      B, RE66325p), oxidative stress metabolism (glutathione S transferase  and
      CG7320), energy metabolism (Act57B), and cytoskeleton formation (actin).  These
      proteins appear to be involved in the resistance response to  trichlorphon.

PMID- 22869078
TI  - In vitro induction  of tetraploid garlic  with trifluralin.
AB  - Garlic  (Allium sativum) is propagated asexually. Since sexual cross breeding is 
      almost impossible, means for effective breeding are not currently available and 
      the available production cultivars are seriously aged and degenerated. A 
      possible alternative for breeding is chemical induction. Trifluralin, a type of 
      herbicide, has been reported to provoke chromosome doubling. However, this 
      chemical had not been tested on garlic. We tested various trifluralin 
      concentrations and treatment durations for efficiency in the induction of 
      tetraploid garlic. A clove base of garlic with a stem cv. Gailiang was used as 
      the ex-plant to induce calluses on Murashige and Skoog (MS) medium; the  calluses
      were then inoculated onto MS medium containing different levels of  trifluralin
      and cultured to induce chromosome number variation in vitro.  Garlic calluses
      were effectively induced via the ex-plant and both shoots and  roots
      differentiated well on MS medium containing 6-benzylaminopurine at 3.0  mg/L and
      indole-3-acetic acid at 0.1 mg/L. However, increases in trifluralin 
      concentration and treatment duration reduced the survival rate and 
      differentiation rate of calluses. Garlic callus cultured for 15 days on medium 
      containing 100 MUM  trifluralin gave the highest rate of chromosome doubling.
      Through observation  of chromosome number in the root apical cells and the
      morphology of guard cells  on the leaf epidermis of the regenerated plantlets, it
      was clear that  chromosome number variation was induced and tetraploids were
      produced in  vitro by trifluralin treatment.

PMID- 22869079
TI  - Alteration of Phascolosoma  esculenta heat shock protein 90 expression under
      heavy metal exposure and thermal stress.
AB  - The full-length complementary DNA (cDNA) of heat shock protein 90 was cloned from
      Phascolosoma esculenta (PeHSP90) using expressed sequence tag and rapid
      amplification of cDNA end approaches. The cDNA of PeHSP90 was 2521 bp including a
      5'-untranslated region of 110 bp, a 3'-untranslated region of 230 bp, and an open
      reading frame of 2181 bp. All of the characteristic motifs of the HSP90 family
      were completely conserved in the deduced amino acid of PeHSP90. The expression of
      PeHSP90 was induced by 3 heavy metals or elevated temperature, under which Zn2+
      displayed effects were more toxic than those of Cd2+ and Cu2+. The polyclonal
      antibodies generated from the recombinant product of PeHSP90 were specifically
      identified not only in the recombinant product but also in the native protein
      from hemocytes. These results strongly suggested that PeHSP90 was involved in
      heavy metal challenge and thermal stress regulation in P. esculenta.

PMID- 22869080
TI  - Isolation and  molecular characterization of a novel strain of Bacillus with
      antifungal  activity from the sorghum rhizosphere.
AB  - We  looked for bacterial strains with antifungal activity in the sorghum 
      rhizosphere. A prescreening procedure to search for hemolytic activity among  the
      isolated strains allowed us to detect good fungitoxic activity in a  bacterial
      isolate that we named UM96. This bacterial isolate showed strong  growth
      inhibition in bioassays against the pathogens Diaporthe phaseolorum,
      Colletotrichum acutatum, Rhizoctonia solani, and Fusarium  oxysporum. The
      supernatant of isolate UM96 also showed strong hemolytic  activity, which was not
      observed in the protease-treated supernatant. However,  the supernatant that was
      treated with protease had similar antagonistic effects  to those exhibited by the
      supernatant that was not treated with this enzyme.  These results suggest that a
      bacteriocin-like compound is responsible for the  hemolytic activity; whereas, as
      far as antifungal effect is concerned, an  antibiotic of nonribosomal origin,
      such as a lipopeptide, might be acting.  Further molecular characterization by
      partial 16S rDNA sequencing placed  isolate UM96 in a cluster with Bacillus
      amyloliquefaciens; however, the  highest identity match found in databases of
      Bacillus species was 91%  identity. This suggests that Bacillus sp UM96 might be
      a novel species.

PMID- 22869081
TI  - Genetic  structure in fragmented populations of Solanum lycocarpum A. St.-Hil. 
      with distinct anthropogenic histories in a Cerrado region of Brazil.
AB  - Solanum  lycocarpum is a woody tree widely distributed in the Cerrado that 
      reaches high population densities in disturbed environments. We examined the 
      genetic diversity and population differentiation of six S. lycocarpum populations
      with different degrees of human disturbance in order to determine if they are 
      negatively affected by anthropogenic activity. Three populations located in 
      southern and three located in southeastern regions of Goias State, Central 
      Brazil, were genotyped with five microsatellite markers. The population located 
      in a protected area had higher number of alleles (26) than the remaining 
      populations (19 to 21 alleles). It indicates that extensive and continuous  areas
      of preserved native vegetation contribute positively to the conservation  of
      genetic diversity, even with S. lycocarpum that easily adapts to  disturbed
      environments. The three southeastern populations, although  fragmented, had
      preserved native vegetation and were not significantly  different from each other
      (thetap =  0.002). All other population pairs compared were significantly
      divergent (thetap varied from  0.03 to 0.11 between pairs, P < 0.05). We found
      three distinct sets of  allele frequencies. The three southeastern populations
      shared similar gene  pools, as well as the two disturbed southern populations,
      which are secondary  vegetation. The southern population located in protected
      area had the most  dissimilar gene pool. In conclusion, populations showing a
      higher degree of  human disturbance tends to show a larger population
      differentiation than  expected from the isolation by distance model, which in the
      current scenario of  the Cerrado destruction points out to a threat to the long
      term conservation of  the species.

PMID- 22869082
TI  - Integrated statistical learning  of metabolic ion mobility spectrometry profiles
      for  pulmonary disease identification.
AB  - Exhaled  air carries information on human health status. Ion mobility
      spectrometers  combined with a multi-capillary column (MCC/IMS) is a well-known
      technology for  detecting volatile organic compounds (VOCs) within human breath.
      This technique  is relatively inexpensive, robust and easy to use in every day
      practice.  However, the potential of this methodology depends on successful
      application of  computational approaches for finding relevant VOCs and
      classification of  patients into disease-specific profile groups based on the
      detected VOCs. We  developed an integrated state-of-the-art system using
      sophisticated statistical  learning techniques for VOC-based feature selection
      and supervised classification  into patient groups. We analyzed breath data from
      84 volunteers, each of them  either suffering from chronic obstructive pulmonary
      disease (COPD), or both  COPD and bronchial carcinoma (COPD + BC), as well as
      from 35 healthy  volunteers, comprising a control group (CG). We standardized and
      integrated  several statistical learning methods to provide a broad overview of
      their  potential for distinguishing the patient groups. We found that there is
      strong  potential for separating MCC/IMS chromatograms of healthy controls and
      COPD  patients (best accuracy COPD vs CG: 94%). However, further examination  of
      the impact of bronchial carcinoma on COPD/no-COPD classification performance  is
      necessary (best accuracy CG vs COPD vs COPD + BC: 79%). We  also extracted 20
      high-scoring VOCs that allowed differentiating COPD patients  from healthy
      controls. We conclude that these statistical learning methods have  a generally
      high accuracy when applied to well-structured, medical MCC/IMS  data.

PMID- 22869083
TI  - Cloning of a phosphatidylinositol  4-kinase gene based on fiber strength
      transcriptome QTL mapping in the cotton  species Gossypium barbadense.
AB  - Sea Island cotton (Gossypium barbadense) is highly valued for its superior fiber
      qualities, especially fiber strength. Based on a transcript-derived fragment
      originated from transcriptome QTL mapping, a fiber strength related candidate
      gene of phosphatidylinositol 4-kinase cDNA, designated as GbPI4K, was first
      cloned, and its expression was characterized in the secondary cell wall
      thickening stage of G. barbadense fibers. The ORF of GbPI4K was found to be 1926
      bp in length and encoded a predicted protein of 641 amino acid residues. The
      putative protein contained a clear PI3/4K kinase catalytic domain and fell into
      the plant type II PI4K cluster in phylogenetic analysis. In this study, the
      expression of cotton PI4K protein was also induced in Escherichia coli BL21 (DE3)
      as a fused protein. Semi-quantitative RT-PCR analysis showed that the gene
      expressed in the root, hypocotyl and leaf of the cotton plants. Real-time RT-PCR
      indicated that this gene in Sea Island cotton fibers expressed 10 days longer
      than that in Upland cotton fibers, and the main expression difference of PI4K
      between Sea Island cotton and Upland cotton in fibers was located in the
      secondary cell wall thickening stage of the fiber. Further analysis indicated
      that PI4K is a crucial factor in the ability of Rac proteins to regulate
      phospholipid signaling pathways.

PMID- 22869084
TI  - Identification and sequence analysis of grain softness protein in selected wheat,
      rye and triticale.
AB  - Grain  softness protein (GSP) is an important protein for overcoming milling and
      grain  defenses in the innate immunity systems of cereals. The objective of this
      study  was to evaluate and understand GSP sequences in selected wheat, rye and 
      triticale. Using sequences for this gene from a sequence database, we performed 
      clustering analysis to compare the sequences obtained from 3 germplasms with 
      other studied sequences for GSP. The maximum difference between the Hirmand GSP 
      genotype in wheat and the database sequences was 23% in EF109396 and EF109399. 
      Most amino acid variation between the GSP sequences involved the same amino 
      acids. The Nikita rye GSP gene showed 64% identity with DQ269918 and  AY667063.
      The isoelectric point in the GSP of wheat and Lasko triticale was  significantly
      higher than that of rye GSP. In addition, parameters such as  optical density,
      grand average of hydrophobicity, percentage of hydrophobicity  and hydrophilic
      amino acids, and number of alpha helices and beta sheets in GSP  were similar in
      wheat and triticale but not in wheat and rye.

PMID- 22869085
TI  - Expression of  the bovine papillomavirus type 1, 2 and 4 L1 genes in the yeast
      Pichia  pastoris.
AB  - Papillomaviruses  are known to cause benign or malignant lesions in various
      animals. In cattle,  bovine papillomavirus (BPV) is the etiologic agent of
      papillomatosis and  neoplasia of the upper gastrointestinal tract and urinary
      bladder. Currently,  there are no standard diagnostic tests or prophylactic
      vaccines. Protection  against papillomavirus infection is conferred by
      neutralizing antibodies  directed towards the major structural protein L1. These
      antibodies can be  efficiently induced by immunization with virus-like particles
      that are formed  spontaneously after L1 gene expression in recombinant systems.
      The yeast Pichia  pastoris is known to provide an efficient system for expression
      of proteins  due to reduced cost and high levels of protein production. We
      evaluated P.  pastoris for expression of the L1 gene from BPV1, BPV2 and BPV4.
      After  methanol induction, the recombinants were able to produce L1 proteins of
      the  three different BPV types. To increase heterologous L1 protein levels, a
      codon  optimization strategy was used for production under bioreactor conditions.
      The  BPV1 L1 protein was identified by monoclonal antibody anti-6xHis. This is
      the  first report of BPV L1 expression in yeast.

PMID- 22869086
TI  - New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent
      Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2
      Phenotypes.
AB  - Cell-based therapies (CBTs) are quickly taking hold as a revolutionary new
      approach to treat many human diseases. Among the cells used in these treatments,
      multipotent mesenchymal stromal cells, also often and imprecisely termed
      mesenchymal stem cells (MSC), are widely used because they are considered
      clinically safe, unique in their immune-modulating capabilities, easily obtained
      from adult tissues, and quickly expanded as well as stored. However, despite
      these established advantages, there are limiting factors to employing MSCs in
      these therapeutic strategies. Foremost is the lack of a general consensus on a
      definition of these cells, marring efforts to prepare homogeneous lots and more
      importantly complicating their in vitro and in vivo investigation. Furthermore,
      although one of the most profound clinical effects of MSC intravenous
      administration is the modulation of host immune responses, no adequate ex vivo
      assays exist to consistently predict the therapeutic effect of each MSC lot in
      the treated patient. Until these issues are addressed, this very promising and
      safe new therapeutic approach cannot be used to its full advantage. However,
      these confounding issues do present exciting opportunities. The first is an
      opportunity to discover unknown aspects of host immune responses because the
      unique effect driven by MSC infusion on a patient's immunity has not yet been
      identified. In addition, there is an opportunity to develop methods, tests, and
      tools to better define MSCs and MSC-based therapy and provide consistency in
      preparation and effect. To this end, my laboratory recently developed a new
      approach to induce uniform pro-inflammatory MSC1 and anti-inflammatory MSC2
      phenotypes from bone marrow-derived MSC preparations. I anticipate that MSC1 and
      MSC2 provide convenient tools with which to address some of these limitations and
      will help advance safe and effective CBTs for human disease. 

PMID- 22869087
TI  - Interactions between mesenchymal stem cells and dendritic cells.
AB  - Mesenchymal stem or stromal cells (MSC) are considered a promising new
      therapeutic strategy for the treatment of several pathological conditions. Due to
      their immunomodulatory properties, they are currently employed in clinical trials
      aimed at preventing or treating steroid-resistant acute graft-versus-host disease
      (GvHD), a frequent complication of allogeneic hematopoietic stem cell
      transplantation (HSCT). In addition, the use of MSC has been proposed for the
      treatment of autoimmune diseases. A number of recent studies have focused on the
      influence of MSC on dendritic cell (DC) function. DCs play a critical role in
      initiating and regulating immune responses by promoting antigen-specific T cell
      activation. Moreover, they are involved in efficient cross-talk with different
      cells of the innate immune system. DC are the most effective antigen-presenting
      cells and prime naive T cells to initiate adaptive immune responses including
      those against allogeneic cells or self-antigens. Thus, alteration of DC
      generation or function may greatly contribute to the inhibition of T cell
      responses. In this context, MSC were shown to interfere with DC maturation from
      monocytes or CD34(+) hemopoietic precursors thus further confirming their role in
      immune regulation and their usefulness in cell-based therapies. 

PMID- 22869088
TI  - Characterization of CpG island DNA methylation of impairment-related genes in a
      rat model of cognitive aging.
AB  - Cognitive abilities, particularly memory formation, vary substantially in the
      elderly, with some individuals exhibiting dramatic decline with age while others
      maintain function well into late life. Epigenetic modifications suggest an
      intriguing mechanism to account for the range of cognitive outcomes in aging as
      they are responsive to environmental influences and affect gene transcription in
      cognitively relevant brain regions. Leveraging a well-characterized rat model of
      neurocognitive aging that recapitulates the range of outcomes seen in humans, we
      previously identified gene expression profiles in the CA3 subregion of the
      hippocampus that distinguish between young and aged subjects as well as between
      impaired and preserved spatial memory function. To investigate the influence of
      epigenetics on these profiles, we examined genomic CpG DNA methylation in the
      promoter regions of three neurophysiologically relevant genes (Gabra5, Hspa5 and
      Syn1) whose expression levels decrease with age and correlate with spatial memory
      performance. Consistent with mRNA decreases, DNA methylation increased in aged
      rats relative to young in CpG dense regions of all target promoters examined.
      However, no correlation with cognition was found. Focused analysis of the Gabra5
      gene found that methylation changes were limited to the CpG island and varied
      substantially across individual CpGs. Methylation at one CpG correlated with
      learning and demonstrated a significant difference between memory impaired aged
      rats and those with intact learning. These data provide evidence that broad age
      dependent DNA methylation changes occur in CpG dense promoter regions of
      cognitively relevant genes but suggest that methylation at single CpGs may be
      more pertinent to individual cognitive differences.

PMID- 22869089
TI  - Predictors of hearing aid use time in children with mild-to-severe hearing loss.
AB  - PURPOSE: This study investigated predictors of hearing aid (HA) use time for
      children with mild-to-severe hearing loss (HL). Barriers to consistent HA use and
      reliability of parent report measures were also examined. METHOD: Participants
      included parents of 272 children with HL. Parents estimated the amount of time
      the child used HAs daily. Regression analysis examined the relationships among
      independent variables and HA use time. To determine parental accuracy of HA use
      time, datalogging from the HAs was compared to the parents' estimates. RESULTS:
      Longer HA use related to older age, poorer hearing, and higher maternal
      education. Parental consistency ratings revealed similar findings--younger
      children and children with milder HL wore HAs less consistently than older
      children and children with more severe HL. Parents' estimates and datalogging
      were significantly correlated; however, results suggested that parents
      overestimate the amount of time their children wear their HAs. CONCLUSION:
      Certain variables were significantly related to the amount of time children wore
      their HAs. Consistency rating scales provided insight into circumstances that
      were challenging for families. Use of both parent reports and datalogging may
      allow clinicians and researchers to obtain a general estimate of HA use time.

PMID- 22869090
TI  - Daptomycin nonsusceptible enterococci in hematologic malignancy and hematopoietic
      stem cell transplant patients: an emerging threat.

PMID- 22869091
TI  - Large pericardial effusion as a life-threatening complication after hematopoietic
      stem cell transplantation-association with chronic GVHD in late-onset adult
      patients.
AB  - Large pericardial effusion (LPE) with cardiac tamponade is a rare but life
      threatening complication in adults undergoing hematopoietic stem cell
      transplantation (HSCT). The incidence and pathophysiology have not been well
      defined. We retrospectively reviewed 601 patients (?18 years of age) receiving
      HSCT (262 autologous, 189 siblings, and 150 unrelated donors) in our center from
      January 2001 to September 2011. We described the incidence, clinical
      characteristics, treatment, and outcome. In total, six patients (0.998 %)
      developed seven episodes (1.16 %) of LPEs with cardiac tamponade. One patient
      underwent unrelated allografts and the other five patients received sibling
      allografts. The median day of detecting LPE were 176 in the six patients and 241
      in the four late-onset patients (range, 9-369). All patients had normal cardiac
      function before HSCT. Two patients developed LPE early after conditioning,
      considered as cardiac toxicity resulting from high-dose cyclophosphamide. Four
      patients had chronic graft-versus-host disease (GVHD) involving lung, skin and
      sicca syndrome concomitant with or preceding the development of LPE. All episodes
      of cardiac tamponade were effectively managed by pericardiocentesis and enhanced
      immunosuppression. In conclusion, LPE and cardiac tamponade may develop after
      allogeneic HSCT, either with sibling or matched unrelated donor. The etiology is
      probably related to chronic GVHD in cases of late onset. Emergent
      pericardiocentesis and enhanced immunosuppression can effectively control this
      life-threatening complication.

PMID- 22869092
TI  - Reproductive outcomes following induced abortion: a national register-based
      cohort study in Scotland.
AB  - OBJECTIVE: To investigate reproductive outcomes in women following induced
      abortion (IA). DESIGN: Retrospective cohort study. SETTING: Hospital admissions
      between 1981 and 2007 in Scotland. PARTICIPANTS: Data were extracted on all women
      who had an IA, a miscarriage or a live birth from the Scottish Morbidity Records.
      A total of 120 033, 457 477 and 47 355 women with a documented second pregnancy
      following an IA, live birth and miscarriage, respectively, were identified.
      OUTCOMES: Obstetric and perinatal outcomes, especially preterm delivery in a
      second ongoing pregnancy following an IA, were compared with those in
      primigravidae, as well as those who had a miscarriage or live birth in their
      first pregnancy. Outcomes after surgical and medical termination as well as after
      one or more consecutive IAs were compared. RESULTS: IA in a first pregnancy
      increased the risk of spontaneous preterm birth compared with that in
      primigravidae (adjusted RR (adj. RR) 1.37, 95% CI 1.32 to 1.42) or women with an
      initial live birth (adj. RR 1.66, 95% CI 1.58 to 1.74) but not in comparison with
      women with a previous miscarriage (adj. RR 0.85, 95% CI 0.79 to 0.91). Surgical
      abortion increased the risk of spontaneous preterm birth compared with medical
      abortion (adj. RR 1.25, 95% CI 1.07 to 1.45). The adjusted RRs (95% CI) for
      spontaneous preterm delivery following two, three and four consecutive IAs were
      0.94 (0.81 to 1.10), 1.06 (0.76 to 1.47) and 0.92 (0.53 to 1.61), respectively.
      CONCLUSIONS: The risk of preterm birth after IA is lower than that after
      miscarriage but higher than that in a first pregnancy or after a previous live
      birth. This risk is not increased further in women who undergo two or more
      consecutive IAs. Surgical abortion appears to be associated with an increased
      risk of spontaneous preterm birth in comparison with medical termination of
      pregnancy. Medical termination was not associated with an increased risk of
      preterm delivery compared to primigravidae.

PMID- 22869095
TI  - The Archives reaches the cloud.

PMID- 22869093
TI  - Candida parapsilosis candidaemia in a neonatal unit over 7 years: a case series
      study.
AB  - OBJECTIVE: To evaluate Candida parapsilosis candidaemia in a neonatal unit over 7
      years. DESIGN: Case series study. SETTING: A 2000-bed tertiary-care university
      hospital at Sao Paulo, Brazil. PARTICIPANTS: Neonates hospitalised in a 63-bed
      neonatal unit. PRIMARY AND SECONDARY OUTCOME MEASURES: We evaluated the incidence
      of C parapsilosis fungemia in a neonatal unit from 2002 through 2008 and the main
      microbiological, clinical and epidemiological aspects of this disease in
      neonates. During the study period an outbreak occurred, an infection control
      programme was implemented, and isolates from blood and hand healthcare workers
      (HCWs) were submitted to molecular typing. RESULTS: During 7 years, there were 36
      cases of C parapsilosis fungaemia and annual incidence varied from 0 to 19.7 per
      1000 admissions. Evaluating 31 neonates with fungemia, the mean age at diagnosis
      was 19 days. All children except for one were premature; all had received total
      parenteral nutrition and all but one had used central venous catheter. Three
      neonates had received antifungal treatment previously to the diagnosis. Thirty
      day mortality was 45%. Only lower birthweight was associated with mortality. C
      parapsilosis species complex was isolated from hand cultures in eight (11%) of
      the HCWs (one isolate was identified as C orthopsilosis). By molecular typing no
      HCW isolate was similar to any of the blood isolates. CONCLUSIONS: The incidence
      of C parapsilosis fungemia in a neonatal unit varied widely over 7 years. We
      observed in our series a higher death rate than that reported in European
      countries and the USA.

PMID- 22869094
TI  - Poor uptake of primary healthcare registration among recent entrants to the UK: a
      retrospective cohort study.
AB  - OBJECTIVES: Uptake of healthcare among migrants is a complex and controversial
      topic; there are multiple recognised barriers to accessing primary care. Delays
      in presentation to healthcare services may result in a greater burden on costly
      emergency care, as well as increased public health risks. This study aimed to
      explore some of the factors influencing registration of new entrants with general
      practitioners (GPs). DESIGN: Retrospective cohort study. SETTING: Port health
      screening at Heathrow and Gatwick airports, primary care. PARTICIPANTS: 252 559
      new entrants to the UK, whose entry was documented by the port health
      tuberculosis screening processes at Heathrow and Gatwick. 191 had insufficient
      information for record linkage. PRIMARY OUTCOME MEASURE: Registration with a GP
      practice within the UK, as measured through record linkage with the Personal
      Demographics Service (PDS) database. RESULTS: Only 32.5% of 252 368 individuals
      were linked to the PDS, suggesting low levels of registration in the study
      population. Women were more likely to register than men, with a RR ratio of 1.44
      (95% CI 1.41 to 1.46). Compared with those from Europe, individuals of
      nationalities from the Americas (0.43 (0.39 to 0.47)) and Africa (0.74 (0.69 to
      0.79)) were less likely to register. Similarly, students (0.83 (0.81 to 0.85)),
      long-stay visitors (0.82 (0.77 to 0.87)) and asylum seekers (0.46 (0.42 to 0.51))
      were less likely to register with a GP than other migrant groups. CONCLUSIONS:
      Levels of registration with GPs within this selected group of new entrants, as
      measured through record linkage, are low. Migrant groups with the lowest
      proportion registered are likely to be those with the highest health needs. The
      UK would benefit from a targeted approach to identify the migrants least likely
      to register for healthcare and to promote access among both users and service
      providers.

PMID- 22869096
TI  - The response to PAK1 inhibitor IPA3 distinguishes between cancer cells with
      mutations in BRAF and Ras oncogenes.
AB  - While new drugs aimed at BRAF-mutated cancers are entering clinical practice,
      cells and tumors with activating Ras mutations are relatively resistant to those
      and quite a few other anti-cancer agents. This inspires the effort to reverse
      this resistance or to uncover new vulnerabilities in such resistant cancers. IPA3
      has been originally identified as a small molecule inhibitor of p21-activated
      protein kinase 1 (PAK1), a candidate therapeutic target in human malignancies. We
      have tested a battery of melanoma and colon carcinoma cell lines that carry
      mutations in BRAF, NRAS and KRAS genes and have observed that those with NRAS and
      KRAS mutations are more sensitive to killing by IPA3. Genetic manipulations
      suggest that the differential response depends not just on these oncogenes, but
      also on additional events that were co-selected during tumor evolution.
      Furthermore, sublethal doses of IPA3 or ectopic expression of dominant-negative
      PAK1 sensitized Ras-mutated cells to GDC-0897 and AZD6244, which otherwise have
      reduced efficiency against cells with activated Ras. Dominant-negative PAK1 also
      reduced the growth of NRAS-mutated cells in confluent cultures, but, unlike IPA3,
      caused no significant toxicity. Although it remains to be proven that all the
      effects of IPA3 are exclusively due to inhibition of PAK1, our findings point to
      the existence of selective vulnerabilities, which are associated with Ras
      mutations and could be useful for better understanding and treatment of a large
      subset of tumors.

PMID- 22869098
TI  - Comparison of free fatty acids composition of cuticular lipids of Calliphora
      vicina larvae and pupae.
AB  - The chemical characterization of the free fatty acid (FFA) fractions of the
      cuticular lipids of Calliphora vicina larvae and pupae was performed by
      separating the FFA fraction using high-performance liquid chromatography with
      laser light scattering detection (HPLC-LLSD) and quantitatively analyzing the FFA
      using gas chromatography-electron impact mass spectrometry (GC-MS). Thirty-two
      saturated and unsaturated FFA were identified and quantified in the insect
      lipids. Cuticular FFA profiles of C. vicina larvae and pupae were compared.
      Cuticular FFA of larvae and pupae accounted for 70.8 and 77.8 % of the total
      lipids, respectively. The cuticular lipids of C. vicina larvae contained 24 FFA
      ranging from 8:0 to 24:0, whereas the cuticular lipids of pupae contained 32 FFA
      ranging from 6:0 to 26:0. The cuticular lipids of the larvae contained 16
      saturated, five monounsaturated, one diunsaturated, and two polyunsaturated FFA.
      The cuticular lipids of the pupae contained 18 saturated, nine monounsaturated,
      two diunsaturated, and three polyunsaturated FFA. The major cuticular FFA in C.
      vicina larvae and pupae was 18:1 (47.6 and 41.7 %, respectively). The highest
      amounts of total cuticular FFA were detected in larvae of C. vicina (1.7 mg/g of
      the insect body). The quantities of total cuticular FFA in pupae were smaller
      (1.4 mg/g of the insect body).

PMID- 22869100
TI  - Whereabouts of an internal short stent placed across the pancreaticojejunostomy
      following pancreatoduodenectomy.
AB  - BACKGROUND/PURPOSE: It is generally thought that an internal short stent placed
      across the pancreaticojejunostomy (PJ) following pancreatoduodenectomy (PD)
      usually passes spontaneously through the rectum thereafter; however, we
      experienced some patients who presented with pancreatitis and cholangitis owing
      to delayed defecation of the stent. The purpose of this study was to clarify when
      the stent eventually became detached from the PJ and how it passed through the
      body until it was finally defecated. In addition, we also investigated the
      factors that may prevent such detachment and defecation. METHODS: This study
      retrospectively analyzed 57 patients who had had internal short stents placed
      across the PJ following PD. Defecation from the body, detachment from the PJ, and
      distal migration of the stent was confirmed by X-ray or computed tomography (CT)
      during the postoperative course. The cumulative rates of defecation and
      detachment of the stents, complications in relation to delayed defecation of the
      stents, and factors predictive of the delayed defecation, delayed detachment, and
      distal migration of the stents were analyzed. RESULTS: Defecation of the stent
      was confirmed in 35 patients. The median time to defecation after PD and the
      cumulative defecation rate at 1 year were 454 days and 41 %, respectively. Acute
      pancreatitis occurred in 2 patients with the stent remaining in the pancreatic
      duct. One patient experienced acute cholangitis owing to migration of the stent
      to the bile duct. Multivariate analysis showed that >=5 stitches in the duct-to
      mucosa anastomosis, stent size of >=5 Fr, and pancreatic fistula classified as
      either Grade B or C were independent predictive factors for delayed defecation of
      the stent. Five or more stitches in the duct-to-mucosa anastomosis was an
      independent predictive factor for delayed detachment of the stent. A stent size
      of >=5 Fr was a risk factor for distal migration of the stent. CONCLUSION: In
      more than half of the study patients, internal short stents were not defecated
      within 1 year. Retrieval of the stent should be considered following the
      migration of an internal short stent. A stent size of >=5 Fr was an independent
      predictive factor for delayed defecation and distal migration of a stent. Five or
      more stitches in the duct-to-mucosa anastomosis was an independent predictive
      factor for delayed defecation and detachment of a stent.

PMID- 22869101
TI  - Changes in the therapeutic strategy for acute cholecystitis after the Tokyo
      guidelines were published.
AB  - BACKGROUND: This study examined the feasibility of early laparoscopic
      cholecystectomy (ELC) for acute cholecystitis (AC) according to the Tokyo
      guidelines severity grade, and analyzed the changes in the therapeutic strategy
      for AC after the Tokyo guidelines were published. METHODS: A total of 225
      patients were enrolled in this study. The therapeutic period was divided into two
      periods: before and after the publication of the Tokyo guidelines (prior to and
      including 2007, and from 2008, respectively). RESULTS: Comparing the surgical
      strategy between ELC and delayed laparoscopic cholecystectomy (DLC), significant
      differences were found in the length of preoperative hospital stay and total
      hospital stay for cases of mild AC compared with moderate AC. With conversion to
      open surgery, postoperative complications including postoperative bile leak were
      not significantly different. Since ELC was performed significantly more often
      after publication of the guidelines, preoperative, postoperative, and total
      hospital stays were significantly shorter in the later period. CONCLUSION: ELC is
      a safe and effective therapeutic strategy for both mild and moderate AC. The
      Tokyo guidelines resulted in a significant increase in the performance of ELC and
      significantly reduced preoperative and total hospital stays without increasing
      intra- and postoperative complications.

PMID- 22869099
TI  - alpha2-3- and alpha2-6- N-linked sialic acids allow efficient interaction of
      Newcastle Disease Virus with target cells.
AB  - Receptor recognition and binding is the first step in the viral cycle. It has
      been established that Newcastle Disease Virus (NDV) interacts with sialylated
      molecules such as gangliosides and glycoproteins at the cell surface.
      Nevertheless, the specific receptor(s) that mediate virus entry are not well
      known. We have analysed the role of the sialic acid linkage in the early steps of
      the viral infection cycle. Pretreatment of ELL-0 cells with both alpha2,3 and
      alpha2,6 specific sialidases led to the inhibition of NDV binding, fusion and
      infectivity, which were restored after alpha2,3(N)- and alpha2,6(N)
      sialyltransferase incubation. Moreover, alpha2,6(N)-sialyltransferases also
      restored NDV activities in alpha2-6-linked sialic acid deficient cells.
      Competition with alpha2-6 sialic acid-binding lectins led to a reduction in the
      three NDV activities (binding, fusion and infectivity) suggesting a role for
      alpha2-6- linked sialic acid in NDV entry. We conclude that both alpha2-3- and
      alpha2-6- linked sialic acid containing glycoconjugates may be used for NDV
      infection. NDV was able to efficiently bind, fuse and infect the ganglioside
      deficient cell line GM95 to a similar extent to that of its parental MEB4,
      suggesting that gangliosides are not essential for NDV binding, fusion and
      infectivity. Nevertheless, the fact that the interaction of NDV with cells
      deficient in N-glycoprotein expression such as Lec1 was less efficient prompted
      us to conclude that NDV requires N-linked glycoproteins for efficient attachment
      and entry into the host cell.

PMID- 22869102
TI  - Comparing adherence to two different HIV antiretroviral regimens: an instrumental
      variable analysis.
AB  - The objective of this observational cohort study was to compare adherence to
      protease inhibitor (PI)-based regimens or non-nucleoside reverse transcriptase
      inhibitor (NNRTI)-based regimens. HIV-seropositive, antiretroviral-naive patients
      initiating therapy between 1998 and 2006 were identified using Veterans Health
      Administration databases. First-year adherence ratios were calculated as
      proportion of days covered (PDC). Multivariable regressions were run with an
      indicator for PDC >95, 90, 85, and 80 % as the dependent variable and an
      indicator for a PI-based regimen as the key independent variable. We controlled
      for residual unmeasured confounding by indication using an instrumental variable
      technique, using the physician's prescribing preference as the instrument. Out of
      929 veterans on PI-based and 747 on NNRTI-based regimens, only 19.7 % of PI
      patients had PDC >80 %, compared to 35.1 % of NNRTI patients. In multivariable
      analysis, starting a PI regimen was significantly associated with poor adherence
      for all 4 adherence thresholds using conventional regressions and instrumental
      variable methods.

PMID- 22869103
TI  - Correlation between pill counts and biologic effects in an HIV-1 prevention
      clinical trial: implications for measuring adherence.
AB  - Clinic-based pill counts of unused study medication are frequently used to
      measure adherence in HIV-1 prevention trials. Monthly pill count adherence data
      from the Partners in Prevention HSV/HIV Transmission Study, a double-blind,
      placebo controlled trial of twice-daily acyclovir suppression of herpes simplex
      virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes
      between 3,381 placebo and active arm participants in two objective biologic
      measures of acyclovir's drug activity: reduction in plasma HIV-1 RNA and HSV-2
      genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated
      with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data
      is strongly correlated with biological effects of adherence. However, when
      calculated adherence exceeded 102 % (i.e., fewer pills returned than expected)
      and when pill counts were missing because bottles were not returned, plasma HIV-1
      RNA and GUD effects were diminished, likely indicating periods of non-adherence.

PMID- 22869104
TI  - Evidence for the reliability and validity of the internalized AIDS-related stigma
      scale in rural Uganda.
AB  - HIV infection remains highly stigmatized throughout sub-Saharan Africa despite
      the increasing availability of treatment. HIV-related stigma is commonly
      described to be highly prevalent in East Africa, but none of these studies have
      employed validated scales for measurement. We used data from 456 people living
      with HIV/AIDS in rural Uganda to validate the six-item Internalized AIDS-Related
      Stigma Scale. The scale demonstrated acceptable internal consistency (Cronbach's
      alpha = 0.73) and time stability. Exploratory factor analysis indicated the
      presence of a single factor. Construct validity was supported by observations
      that the scale was correlated with related constructs such as depression and
      mental health-related quality of life. The scale was able to discriminate between
      groups of persons who were different in terms of treatment status and their
      experience of HIV-related self-blame. Taken together, these findings suggest that
      the Internalized AIDS-Related Stigma Scale may be a useful tool for socio
      behavioral HIV research.

PMID- 22869105
TI  - Should I stay or should I go: protection and maintenance of DNA methylation at
      imprinted genes.
AB  - Recent findings shed light on the coordination of two fundamental, yet
      mechanistically opposing, processes in the early mammalian embryo. During the
      oocyte-to-embryo transition and early preimplantation development nuclear
      reprogramming occurs. This resetting of the epigenome in maternal and paternal
      pronuclei to a ground state is the essential step ensuring totipotency in the
      zygote, the first embryonic stage. Radical, global DNA demethylation, which
      occurs actively in the paternal and passively in the maternal genome, is a
      prominent feature of nuclear reprogramming; yet, this process poses a danger to a
      subset of methylated sequences that must be preserved for their germline to soma
      inheritance. Genomic imprinting and its importance were demonstrated three
      decades ago by a series of experiments generating non-viable mammalian
      uniparental embryos. Indeed, imprinted loci, gene clusters with parent-of-origin
      specific gene expression patterns, must retain their differential methylation
      status acquired during gametogenesis throughout embryogenesis and in adult
      tissues. It is just recently that the molecular players that protect/maintain
      imprinting marks during reprogramming in preimplantation embryos have been
      identified, in particular, an epigenetic modifier complex formed by ZFP57 and
      TRIM28/KAP1. The interaction of these and other molecules with the newly formed
      embryonic chromatin and imprinted genes is discussed and highlighted herein.

PMID- 22869106
TI  - Utilizing the estrogen receptor ligand-binding domain for controlled protein
      translocation to the insoluble fraction.
AB  - PURPOSE: The estrogen receptor forms insoluble aggregates in the insoluble
      cytoskeletal subcellular fraction when bound to the antagonist fulvestrant. The
      ligand-binding domain was isolated and fused to signal sequences to target
      subcellular compartments. Sequestering a pro-apoptotic peptide tested the utility
      of a protein targeted to the insoluble fraction. METHODS: The ligand-binding
      domain of the estrogen receptor was isolated and fused with signal sequences,
      either a nuclear localization signal or nuclear export signal. The subcellular
      localization when bound to drug fulvestrant was examined, specifically its
      interaction with cytokeratins 8 and 18. The ability to target a therapeutic
      peptide to the insoluble fraction was tested by fusing a therapeutic coiled-coil
      from Bcr-Abl in K562 cells. RESULTS: The estrogen receptor ligand-binding domain
      responds to fulvestrant by translocating to the insoluble fraction. Adding a
      signal sequence significantly limited the translocation to either the nucleus or
      cytoplasm. The cytokeratin 8/18 status of the cell did not alter this response.
      The therapeutic coiled-coil fused to ERLBD was inactivated upon ligand induction.
      CONCLUSIONS: Isolating the ligand-binding domain of the estrogen receptor creates
      a ligand-controllable protein capable of translocation to the insoluble fraction.
      This can be used to sequester an active peptide to alter its function.

PMID- 22869107
TI  - Assessment of iontophoretic and passive ungual penetration by laser scanning
      confocal microscopy.
AB  - PURPOSE: To estimate the in vitro ungual penetration depth of sodium fluorescein
      and nile blue chloride by laser scanning confocal microscopy. METHODS: The depth,
      uniformity and pathways of penetration of both markers into human nail during
      passive and iontophoretic experiments were investigated. The penetration of
      sodium fluorescein into the dorsal, ventral and intermediate layers of the nail
      was also studied. Transversal images were used to estimate directly the relative
      penetration of the markers with respect to the complete thickness of the nail.
      "Exposed layer" images allowed estimating the depth of penetration by taking xy
      plans, starting by the exposed layer, and following the z axis into the nail.
      RESULTS: The fluorescent markers penetrated 7-12% of the nail thickness.
      Iontophoresis increased penetration of both markers compared to passive
      diffusion. However, ungual penetration was not modified by the intensity of
      current applied. Penetration into the dorsal, ventral, and intermediate nail
      layers was similar. The method developed allowed inter- and intra- nail
      variability to be accounted for. CONCLUSIONS: Iontophoresis enhanced moderately
      the penetration of the two markers into the nail plate as compared to passive
      diffusion. The confocal images suggested the transcellular pathway to be
      predominant during both passive and iontophoretic experiments.

PMID- 22869108
TI  - Structural characterization of recombinant crustacyanin subunits from the lobster
      Homarus americanus.
AB  - Crustacean crustacyanin proteins are linked to the production and modification of
      carapace colour, with direct implications for fitness and survival. Here, the
      structural and functional properties of the two recombinant crustacyanin subunits
      H(1) and H(2) from the American lobster Homarus americanus are reported. The two
      subunits are structurally highly similar to the corresponding natural apo
      crustacyanin CRTC and CRTA subunits from the European lobster H. gammarus.
      Reconstitution studies of the recombinant crustacyanin proteins H(1) and H(2)
      with astaxanthin reproduced the bathochromic shift of 85-95 nm typical of the
      natural crustacyanin subunits from H. gammarus in complex with astaxanthin.
      Moreover, correlations between the presence of crustacyanin genes in crustacean
      species and the resulting carapace colours with the spectral properties of the
      subunits in complex with astaxanthin confirmed this genotype-phenotype linkage.

PMID- 22869109
TI  - Structure of Aeropyrum pernix fibrillarin in complex with natively bound S
      adenosyl-L-methionine at 1.7 A resolution.
AB  - Fibrillarin is the key methyltransferase associated with the C/D class of small
      nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of
      pre-ribosomal rRNA processing. This molecule is found in the fibrillar regions of
      the eukaryotic nucleolus and is involved in methylation of the 2'-O atom of
      ribose in rRNA. Human fibrillarin contains an N-terminal GAR domain, a central
      RNA-binding domain comprising an RNP-2-like superfamily consensus sequence and a
      catalytic C-terminal helical domain. Here, Aeropyrum pernix fibrillarin is
      described, which is homologous to the C-terminal domain of human fibrillarin. The
      protein was crystallized with an S-adenosyl-L-methionine (SAM) ligand bound in
      the active site. The molecular structure of this complex was solved using X-ray
      crystallography at a resolution of 1.7 A using molecular replacement with
      fibrillarin structural homologs. The structure shows the atomic details of SAM
      and its active-site interactions; there are a number of conserved residues that
      interact directly with the cofactor. Notably, the adenine ring of SAM is
      stabilized by pi-pi interactions with the conserved residue Phe110 and by
      electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The pi-pi
      interaction appears to play a critical role in stabilizing the association of SAM
      with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with
      homologous structures revealed different orientations of Phe110 and changes in
      alpha-helix 6 of fibrillarin and suggests key differences in its interactions
      with the adenine ring of SAM in the active site and with the C/D RNA. These
      differences may play a key role in orienting the SAM ligand for catalysis as well
      as in the assembly of other ribonucleoproteins and in the interactions with C/D
      RNA.

PMID- 22869110
TI  - Flexibility of the P-loop of Pim-1 kinase: observation of a novel conformation
      induced by interaction with an inhibitor.
AB  - The serine/threonine kinase Pim-1 is emerging as a promising target for cancer
      therapeutics. Much attention has recently been focused on identifying potential
      Pim-1 inhibitor candidates for the treatment of haematopoietic malignancies. The
      outcome of a rational drug-design project has recently been reported [Nakano et
      al. (2012), J. Med. Chem. 55, 5151-5156]. The report described the process of
      optimization of the structure-activity relationship and detailed from a medicinal
      chemistry perspective the development of a low-potency and nonselective compound
      initially identified from in silico screening into a potent, selective and
      metabolically stable Pim-1 inhibitor. Here, the structures of the initial in
      silico hits are reported and the noteworthy features of the Pim-1 complex
      structures are described. A particular focus was placed on the rearrangement of
      the glycine-rich P-loop region that was observed for one of the initial
      compounds, (Z)-7-(azepan-1-ylmethyl)-2-[(1H-indol-3-yl)methylidene]-6-hydroxy-1
      benzofuran-3(2H)-one (compound 1), and was also found in all further derivatives.
      This novel P-loop conformation, which appears to be stabilized by an additional
      interaction with the beta3 strand located above the binding site, is not usually
      observed in Pim-1 structures.

PMID- 22869112
TI  - Anomalous dispersion analysis of inhibitor flexibility: a case study of the
      kinase inhibitor H-89.
AB  - With its ability to show the interactions between drug-target proteins and small
      molecule ligands, X-ray crystallography is an essential tool in drug-discovery
      programmes. However, its usefulness can be limited by crystallization artifacts
      or by the data resolution, and in particular when assumptions of unimodal binding
      (and isotropic motion) do not apply. Discrepancies between the modelled crystal
      structure and the physiological range of structures generally prevent
      quantitative estimation of binding energies. Improved crystal structure
      resolution will often not aid energy estimation because the conditions which
      provide the highest rigidity and resolution are not likely to reflect
      physiological conditions. Instead, strategies must be employed to measure and
      model flexibility and multiple binding modes to supplement crystallographic
      information. One useful tool is the use of anomalous dispersion for small
      molecules that contain suitable atoms. Here, an analysis of the binding of the
      kinase inhibitor H-89 to protein kinase A (PKA) is presented. H-89 contains a
      bromobenzene moiety that apparently binds with multiple conformations in the
      kinase ATP pocket. Using anomalous dispersion methods, it was possible to resolve
      these conformations into two distinct binding geometries.

PMID- 22869111
TI  - Structure of human Rack1 protein at a resolution of 2.45 A.
AB  - The crystal structure of human receptor for activated C-kinase 1 (hRack1) protein
      is reported at 2.45 A resolution. The crystals belongs to space group P4(1)2(1)2,
      with three molecules per asymmetric unit. The hRack1 structure features a
      sevenfold beta-propeller, with each blade housing a sequence motif that contains
      a strictly conserved Trp, the indole group of which is embedded between adjacent
      blades. In blades 1-5 the imidazole group of a His residue is wedged between the
      side chains of a Ser residue and an Asp residue through two hydrogen bonds. The
      hRack1 crystal structure forms a starting basis for understanding the remarkable
      scaffolding properties of this protein.

PMID- 22869113
TI  - Structure of a fluorescent protein from Aequorea victoria bearing the obligate
      monomer mutation A206K.
AB  - The green fluorescent protein (GFP) from the jellyfish Aequoria victoria has been
      shown to dimerize at high concentrations, which could lead to artefacts in
      imaging experiments. To ensure a truly monomeric state, an A206K mutation has
      been introduced into most of its widely used variants, with minimal effect on the
      spectroscopic properties. Here, the first structure of one of these variants, the
      cyan fluorescent protein mTurquoise, is presented and compared with that of its
      dimeric version mTurquoise-K206A. No significant structural change is detected in
      the chromophore cavity, reinforcing the notion that this mutation is
      spectroscopically silent and validating that the structural analysis performed on
      dimeric mutants also applies to monomeric versions. Finally, it is explained why
      cyan versions of GFP containing the Y66W and N146I mutations do not require the
      A206K mutation to prevent dimerization at high concentrations.

PMID- 22869114
TI  - A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1)
      in complex with adenosine 5'-monophosphate at 1.38 A resolution.
AB  - Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient
      and widespread branch of the histidine triad protein superfamily. HINT1 plays an
      important role in various biological processes and has been found in many
      species. Here, the structure of the human HINT1-adenosine 5'-monophosphate (AMP)
      complex at 1.38 A resolution obtained from a new monoclinic crystal form is
      reported. The final structure has R(cryst) = 0.1207 (R(free) = 0.1615) and the
      model exhibits good stereochemical quality. Detailed analysis of the high
      resolution data allowed the details of the protein structure to be updated in
      comparison to the previously published data.

PMID- 22869115
TI  - Binding of the unreactive substrate analog L-2-amino-3-guanidinopropionic acid
      (dinor-L-arginine) to human arginase I.
AB  - Human arginase I (HAI) is a binuclear manganese metalloenzyme that catalyzes the
      hydrolysis of L-arginine to form L-ornithine and urea through a metal-activated
      hydroxide mechanism. Since HAI regulates L-Arg bioavailability for NO
      biosynthesis, it is a potential drug target for the treatment of cardiovascular
      diseases such as atherosclerosis. X-ray crystal structures are now reported of
      the complexes of Mn(2)(2+)-HAI and Co(2)(2+)-HAI with L-2-amino-3
      guanidinopropionic acid (AGPA; also known as dinor-L-arginine), an amino acid
      bearing a guanidinium side chain two methylene groups shorter than that of L
      arginine. Hydrogen bonds to the alpha-carboxylate and alpha-amino groups of AGPA
      dominate enzyme-inhibitor recognition; the guanidinium group does not interact
      directly with the metal ions.

PMID- 22869116
TI  - Crystallization and preliminary crystallographic studies of the YafN-YafO complex
      from Escherichia coli.
AB  - The ribosome-dependent mRNA interferase YafO from Escherichia coli belongs to a
      type II toxin-antitoxin (TA) system and its cognate antitoxin YafN neutralizes
      cell toxicity by forming a stable YafN-YafO complex. The YafN-YafO TA system is
      upregulated by the SOS response (a global response to DNA damage in which the
      cell cycle is arrested and mutagenesis is induced) and may then inhibit protein
      synthesis by endoribonuclease activity of YafO with the 50S ribosome subunit.
      Structural information on the YafN-YafO complex and related complexes would be
      helpful in order to understand the structural basis of the mechanism of mRNA
      recognition and cleavage, and the assembly of these complexes. Here, the YafN
      YafO complex was expressed and crystallized. Crystals grown by the hanging-drop
      vapour-diffusion method diffracted to 3.50 A resolution and belonged to the
      hexagonal space group P622, with unit-cell parameters a = 86.14, b = 86.14, c =
      173.11 A, alpha = beta = 90, gamma = 120 degrees . Both Matthews coefficient
      analysis and the self-rotation function suggested the presence of one molecule
      per asymmetric unit in the crystal, with a solvent content of 65.69% (V(M) = 3.58
      A(3) Da(-1)).

PMID- 22869117
TI  - Expression, crystallization and preliminary crystallographic data analysis of
      PigF, an O-methyltransferase from the prodigiosin-synthetic pathway in Serratia.
AB  - Prodigiosin, which is a member of the prodiginines, is a red linear tripyrrole
      compound. A gene cluster for the biosynthesis of prodigiosin has been identified
      in Serratia and most genes in the cluster have been functionally assigned. A
      bifurcated biosynthetic pathway for prodigiosin has previously been determined.
      The last step in the biosynthetic pathway of 4-methoxy-2,2'-bipyrrole-5
      carbaldehyde (MBC) is catalyzed by PigF, which transfers a methyl group to 4
      hydroxy-2,2'-bipyrrole-5-carbaldehyde (HBC) to form the terminal product MBC, but
      its catalytic mechanism is not known. To elucidate its mechanism, recombinant
      PigF was purified and crystallized. The crystals belonged to space group P2(1),
      with unit-cell parameters a = 69.4, b = 52.4, c = 279.2 A, beta = 96.8 degrees .
      The native crystals may contain six molecules in the asymmetric unit, with a V(M)
      of 2.17 A(3) Da(-1) and a solvent content of 43.43%. A full data set was
      collected at 2.6 A resolution using synchrotron radiation on beamline BL17U of
      Shanghai Synchrotron Radiation Facility (SSRF), People's Republic of China.
      Molecular replacement was unsuccessful. To solve the structure of PigF by
      experimental phasing, selenomethionine-derivativized protein crystals were
      prepared from a condition with 0.01 M spermidine as an additive. One crystal
      diffracted to 1.9 A resolution and a full data set was collected on beamline
      BL17U at SSRF. The crystal belonged to space group P2(1), with unit-cell
      parameters a = 69.0, b = 52.9, c = 93.4 A, beta = 97.3 degrees . Heavy-atom
      substructure determination and phasing by SAD clearly showed that the crystal
      contains two molecules in the asymmetric unit, with a V(M) of 2.19 A(3) Da(-1)
      and a solvent content of 43.82%.

PMID- 22869118
TI  - Crystallization and preliminary X-ray studies of ferric uptake regulator from
      Magnetospirillum gryphiswaldense.
AB  - Magnetosomes in magnetotactic bacteria have been widely used in studies of
      magnetic domains and in commercial applications. The iron content of
      magnetotactic bacteria is ~100 times higher than that of Escherichia coli.
      Magnetospirillum gryphiswaldense MSR-1 can still take up iron even at high
      intracellular concentrations. Ferric uptake regulator (Fur) is a global iron
      responsive regulator that affects magnetosome formation, iron transport and
      oxygen metabolism. However, the mechanism of iron uptake and homeostasis by M.
      gryphiswaldense MSR-1 Fur is not clear. Here, the expression, purification and
      crystallization of apo and SeMet Fur from M. gryphiswaldense MSR-1 are reported.
      The crystals belonged to space group C2. Matthews coefficient analysis and size
      exclusion chromatography showed that the asymmetric unit probably contains one
      dimer of Fur. Diffraction data were optimized to 1.58 A resolution for apo Fur
      and to 1.9 A resolution for SeMet Fur.

PMID- 22869119
TI  - Crystallization studies of the murine c-di-GMP sensor protein STING.
AB  - The innate immune response is the first defence system against pathogenic
      microorganisms, and cytosolic detection of pathogen-derived DNA is believed to be
      one of the major mechanisms of interferon production. Recently, the mammalian ER
      membrane protein STING (stimulator of IFN genes; also known as MITA, ERIS, MPYS
      and TMEM173) has been found to be the master regulator linking the detection of
      cytosolic DNA to TANK-binding kinase 1 (TBK1) and its downstream transcription
      factor IFN regulatory factor 3 (IRF3). In addition, STING itself was soon
      discovered to be a direct sensor of bacterial cyclic dinucleotides such as c-di
      GMP or c-di-AMP. However, structural studies of apo STING and its complexes with
      these cyclic dinucleotides and with other cognate binding proteins are essential
      in order to fully understand the roles played by STING in these crucial
      signalling pathways. In this manuscript, the successful crystallization of the C
      terminal domain of murine STING (STING-CTD; residues 138-344) is reported. Native
      and SeMet-labelled crystals were obtained and diffracted to moderate resolutions
      of 2.39 and 2.2 A, respectively.

PMID- 22869120
TI  - Crystallization and preliminary X-ray diffraction analysis of a novel type of
      phosphoserine phosphatase from Hydrogenobacter thermophilus TK-6.
AB  - Two novel-type phosphoserine phosphatases (PSPs) with unique substrate
      specificity from the thermophilic and hydrogen-oxidizing bacterium
      Hydrogenobacter thermophilus TK-6 have previously been identified. Here, one of
      the PSPs (iPSP1) was heterologously expressed in Escherichia coli, purified and
      crystallized. Diffraction-quality crystals were obtained by the sitting-drop
      vapour-diffusion method using PEG 4000 as the precipitant. Two diffraction data
      sets with resolution ranges of 45.0-2.50 and 45.0-1.50 A were collected from a
      single crystal and were merged to give a highly complete data set. The space
      group of the crystal was identified as primitive orthorhombic P2(1)2(1)2(1), with
      unit-cell parameters a = 49.8, b = 73.6, c = 124.3 A. The calculated Matthews
      coefficient (V(M) = 2.32 A(3) Da(-1)) indicated that the crystal contained one
      iPSP1 complex per asymmetric unit.

PMID- 22869121
TI  - Crystallization and preliminary X-ray diffraction analysis of a novel GH120 beta
      xylosidase (XylC) from Thermoanaerobacterium saccharolyticum JW/SL-YS485.
AB  - Xylosidases hydrolyze xylopolymers at the nonreducing end to free xylose units.
      The beta-xylosidase (XylC) from Thermoanaerobacterium saccharolyticum JW/SL-YS485
      was expressed in Escherichia coli and the recombinant protein was purified and
      crystallized. A BLASTP search with the XylC protein sequence showed that no
      similar structure had previously been solved. XylC was classified as a member of
      the new glycoside hydrolase family GH120 according to the CAZy website
      (http://www.cazy.org/). Crystals belonging to the monoclinic space group P2(1),
      with unit-cell parameters a = 88.36, b = 202.20, c = 99.87 A, beta = 99.04
      degrees , were obtained by the sitting-drop vapour-diffusion method and
      diffracted to 2.2 A resolution. Structure determination using MIR and MAD methods
      is in progress.

PMID- 22869122
TI  - Crystallization and preliminary X-ray analysis of the receiver domain of a
      putative response regulator, BPSL0128, from Burkholderia pseudomallei.
AB  - bpsl0128, a gene encoding a putative response regulator from Burkholderia
      pseudomallei strain D286, has been cloned into a pETBLUE-1 vector system,
      overexpressed in Escherichia coli and purified. The full-length protein is
      degraded during purification to leave a fragment corresponding to the putative
      receiver domain, and crystals of this protein that diffracted to beyond 1.75 A
      resolution have been grown by the hanging-drop vapour-diffusion technique using
      PEG 6000 as the precipitant. The crystals belonged to one of the enantiomorphic
      pair of space groups P3(1)21 and P3(2)21, with unit-cell parameters a = b =
      65.69, c = 105.01 A and either one or two molecules in the asymmetric unit.

PMID- 22869123
TI  - Cloning, expression, purification and preliminary X-ray analysis of a putative
      metagenome-derived lipase.
AB  - LipS is a novel thermostable putative lipase that was isolated from a metagenomic
      library using functional screening methods. The corresponding gene shows high
      similarity to that encoding a putative but uncharacterized esterase from
      Symbiobacterium thermophilum IAM14863 (99% nucleotide-sequence similarity). Two
      different constructs of the recombinant lipase were crystallized. Crystals
      belonging to space group P4(2)2(1)2 diffracted X-ray radiation to 2.8 A
      resolution and crystals belonging to space group P4 diffracted to 2.0 A
      resolution. The most probable content of their asymmetric units were two
      molecules (P4(2)2(1)2) and four or five molecules (P4), respectively.

PMID- 22869124
TI  - Crystallization and preliminary crystallographic analysis of the C-terminal
      domain of MamM, a magnetosome-associated protein from Magnetospirillum
      gryphiswaldense MSR-1.
AB  - MamM is a unique magnetosome-associated protein that shares substantial homology
      with cation diffusion facilitator (CDF) proteins, a group of heavy-metal-ion
      efflux transporters that participate in metal-ion homeostasis in all domains of
      life. Magnetotactic bacteria utilize CDF proteins in iron-oxide biomineralization
      and in magnetosome formation. Here, the crystallization and preliminary X-ray
      analysis of recombinant Magnetospirillum gryphiswaldense MamM is reported. The C
      terminal domain of MamM was crystallized in the orthorhombic space group C222(1),
      with unit-cell parameters a = 37.1, b = 94.0, c = 53.3 A. X-ray diffraction data
      were collected to a resolution of 2.0 A.

PMID- 22869125
TI  - Purification, crystallization and preliminary crystallographic analysis of banyan
      peroxidase.
AB  - Plant peroxidases are extensively used in a wide range of biotechnological
      applications owing to their high environmental and thermal stability. A new
      peroxidase, named banyan peroxidase, was purified from the latex of Ficus
      benghalensis and crystallized. X-ray diffraction data were collected from native
      crystals and from bromide and xenon derivatives to resolutions of up to 1.66 A in
      the trigonal space group P3(2)21, with unit-cell parameters a = b = 73.1, c =
      164.6 A. The anomalous signal of the intrinsic iron and calcium ions was
      sufficient for structure solution by SAD, although the sequence is not yet known.

PMID- 22869126
TI  - Crystallization and preliminary X-ray diffraction analysis of three myotoxic
      phospholipases A2 from Bothrops brazili venom.
AB  - Two myotoxic and noncatalytic Lys49-phospholipases A(2) (braziliantoxin-II and MT
      II) and a myotoxic and catalytic phospholipase A(2) (braziliantoxin-III) from the
      venom of the Amazonian snake Bothrops brazili were crystallized. The crystals
      diffracted to resolutions in the range 2.56-2.05 A and belonged to space groups
      P3(1)21 (braziliantoxin-II), P6(5)22 (braziliantoxin-III) and P2(1) (MT-II). The
      structures were solved by molecular-replacement techniques. Both of the Lys49
      phospholipases A(2) (braziliantoxin-II and MT-II) contained a dimer in the
      asymmetric unit, while the Asp49-phospholipase A(2) braziliantoxin-III contained
      a monomer in its asymmetric unit. Analysis of the quaternary assemblies of the
      braziliantoxin-II and MT-II structures using the PISA program indicated that both
      models have a dimeric conformation in solution. The same analysis of the
      braziliantoxin-III structure indicated that this protein does not dimerize in
      solution and probably acts as a monomer in vivo, similar to other snake-venom
      Asp49-phospholipases A(2).

PMID- 22869127
TI  - Useable diffraction data from a multiple microdomain-containing crystal of
      Ascaris suum As-p18 fatty-acid-binding protein using a microfocus beamline.
AB  - As-p18 is a fatty-acid-binding protein from the parasitic nematode Ascaris suum.
      Although it exhibits sequence similarity to mammalian intracellular fatty-acid
      binding proteins, it contains features that are unique to nematodes. Crystals
      were obtained, but initial diffraction data analysis revealed that they were
      composed of a number of 'microdomains'. Interpretable data could only be
      collected using a microfocus beamline with a beam size of 12 * 8 um.

PMID- 22869128
TI  - Purification, crystallization and preliminary X-ray analysis of the IgV domain of
      human nectin-4.
AB  - Nectin-4 belongs to a family of immunoglobulin-like cell adhesion molecules and
      is highly expressed in cancer cells. Recently, nectin-4 was found to be a
      receptor of measles virus and the IgV domain sustains strong binding to measles
      virus H protein. In this study, the successful expression and purification of
      human nectin-4 V domain (nectin-4v) is reported. The purified protein was
      crystallized using the sitting-drop vapour-diffusion method. The crystals
      diffracted to 1.8 A resolution and belonged to space group P2(1), with unit-cell
      parameters a = 33.1, b = 51.7, c = 56.9 A, beta = 94.7 degrees . Preliminary
      analysis of the diffraction data was also performed.

PMID- 22869129
TI  - Purification, crystallization and preliminary X-ray analysis of the DNA-binding
      domain of AdpA, the central transcription factor in the A-factor regulatory
      cascade in the filamentous bacterium Streptomyces griseus, in complex with a
      duplex DNA.
AB  - Streptomyces griseus AdpA is the central transcription factor in the A-factor
      regulatory cascade and activates a number of genes that are required for both
      secondary metabolism and morphological differentiation, leading to the onset of
      streptomycin biosynthesis as well as aerial mycelium formation and sporulation.
      The DNA-binding domain of AdpA consists of two helix-turn-helix DNA-binding
      motifs and shows low nucleotide-sequence specificity. To reveal the molecular
      basis of the low nucleotide-sequence specificity, an attempt was made to obtain
      cocrystals of the DNA-binding domain of AdpA and several kinds of duplex DNA. The
      best diffracting crystal was obtained using a 14-mer duplex DNA with two
      nucleotide overhangs at the 5'-ends. The crystal diffracted X-rays to 2.8 A
      resolution and belonged to space group C222(1), with unit-cell parameters a =
      76.86, b = 100.96, c = 101.25 A. The Matthews coefficient (V(M) = 3.71 A(3) Da(
      1)) indicated that the crystal was most likely to contain one DNA-binding domain
      of AdpA and one duplex DNA in the asymmetric unit, with a solvent content of
      66.8%.

PMID- 22869130
TI  - Characterization of crystals of an antibody-recognition fragment of the cancer
      differentiation antigen mesothelin in complex with the therapeutic antibody MORAb
      009.
AB  - The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the
      binding of mesothelin to CA-125 and displays promising anticancer potential. It
      is currently undergoing clinical trials. In order to understand the basis of the
      interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab
      fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment
      of mesothelin (residues 7-64) were crystallized. The crystals of the Fab
      diffracted X-rays to 1.75 A resolution and had the symmetry of space group
      P4(1)2(1)2, with unit-cell parameters a = b = 140.6, c = 282.0 A. The crystals of
      the mesothelin-Fab complex diffracted to 2.6 A resolution and belonged to the
      hexagonal space group P6(4), with unit-cell parameters a = b = 146.2, c = 80.9 A.
      Structural analyses of these molecules are in progress.

PMID- 22869131
TI  - Cloning, purification, crystallization and preliminary X-ray diffraction studies
      of Escherichia coli PapD-like protein (EcpD).
AB  - Many Gram-negative bacteria are characterized by hair-like proteinaceous
      appendages on their surface known as fimbriae. In uropathogenic strains of
      Escherichia coli, fimbriae mediate attachment by binding to receptors on the host
      cell, often contributing to virulence and disease. E. coli PapD-like protein
      (EcpD) is a periplasmic chaperone that plays an important role in the proper
      folding and guiding of Yad fimbrial proteins to the outer membrane usher protein
      in a process known as pilus biogenesis. EcpD is essential for pilus biogenesis in
      uropathogenic E. coli and plays an important role in virulence. In the present
      study, EcpD was cloned, overexpressed, purified and crystallized by the hanging
      drop vapour-diffusion method. The crystals diffracted to 1.67 A resolution and
      belonged to the orthorhombic space group C222(1), with unit-cell parameters a =
      100.3, b = 127.6, c = 45.9 A. There was a single molecule in the asymmetric unit
      and the corresponding Matthews coefficient was calculated to be 3.02 A(3) Da(-1),
      with 59% solvent content. Initial phases were determined by molecular
      replacement.

PMID- 22869132
TI  - Expression, purification, crystallization and preliminary X-ray analysis of 4
      hydroxy-3-methyl-2-keto-pentanoate aldolase (asHPAL) from Arthrobacter simplex
      strain AKU 626.
AB  - 4-Hydroxy-3-methyl-2-keto-pentanoate aldolase (asHPAL), an enzyme used in the
      synthesis of (2S,3R,4S)-4-hydroxyisoleucine, was crystallized in the absence and
      the presence of 2-ketobutyrate as one of its substrates by the sitting-drop
      vapour-diffusion method using PEG 400 as a precipitant. Crystals of asHPAL grown
      without and with 2-ketobutyrate diffracted to 1.60 and 1.55 A resolution and
      belonged to space group C2, with unit-cell parameters a = 116.8, b = 88.2, c =
      85.3 A, beta = 122.3 degrees  and a = 116.2, b = 88.1, c = 85.0 A, beta = 122.3
      degrees , respectively.

PMID- 22869133
TI  - Crystallization and X-ray diffraction analysis of the ternary complex of the C
      terminal domain of human REV1 in complex with REV7 bound to a REV3 fragment
      involved in translesion DNA synthesis.
AB  - REV1, REV3 and REV7 are pivotal proteins in translesion DNA synthesis that allows
      DNA synthesis to continue even in the presence of DNA damage. REV1 and REV3 are
      error-prone DNA polymerases, while REV7 acts as an adaptor protein that links
      them together. A ternary complex of the C-terminal domain of human REV1 in
      complex with REV7 bound to a REV3 fragment has been crystallized. The crystals
      belonged to space group P3(1)21, with unit-cell parameters a = b = 74.7, c =
      124.5 A.

PMID- 22869134
TI  - Expression, purification and preliminary crystallographic analysis of Drosophila
      melanogaster lysosomal alpha-mannosidase.
AB  - The lysosomal alpha-mannosidases are class II mannosidases that belong to
      glycoside hydrolase family 38 and play an important role in the degradation of
      asparagine-linked carbohydrates of glycoproteins. Based on peptide similarity to
      human and bovine lysosomal mannosidase (LM), recombinant alpha-mannosidase from
      Drosophila melanogaster (dLM408) was cloned and heterologously expressed in
      Pichia pastoris. The recombinant form of dLM408 designed for structural analysis
      lacks the transmembrane domain and was crystallized using standard vapour
      diffusion and counter-diffusion techniques. The crystals grew as flat plates and
      as tetragonal bipyramids, respectively. The plate-shaped crystals exhibited the
      symmetry of space group P2(1)2(1)2(1) and diffracted to a minimum d-spacing of
      3.5 A.

PMID- 22869135
TI  - Crystallization and preliminary X-ray analysis of Pac17 from the pacidamycin
      biosynthetic cluster of Streptomyces coeruleorubidus.
AB  - Pac17 is an uncharacterized protein from the pacidamycin gene cluster of the soil
      bacterium Streptomyces coeruleorubidus. It is implicated in the biosynthesis of
      the core diaminobutyric acid residue of the antibiotic, although its precise role
      is uncertain at present. Given that pacidamycins inhibit translocase I of
      Pseudomonas aeruginosa, a clinically unexploited antibiotic target, they offer
      new hope in the search for antibacterial agents directed against this important
      pathogen. Crystals of Pac17 were grown by vapour diffusion and X-ray data were
      collected at a synchrotron to a resolution of 1.9 A from a single crystal. The
      crystal belonged to space group C2, with unit-cell parameters a = 214.12, b =
      70.88, c = 142.22 A, beta = 92.96 degrees . Preliminary analysis of these data
      suggests that the asymmetric unit consists of one Pac17 homotetramer, with an
      estimated solvent content of 49.0%.

PMID- 22869136
TI  - Crystallization and preliminary X-ray diffraction analysis of a fatty-acid
      metabolism regulatory protein, FadR, from Bacillus halodurans.
AB  - FadR is an acyl-CoA-dependent transcription factor which regulates genes encoding
      proteins involved in fatty-acid degradation and synthesis in order to maintain
      lipid homeostasis. FadR from the alkaliphilic bacterium Bacillus halodurans was
      cloned and overexpressed in Escherichia coli. The FadR (Bh3102) protein from B.
      halodurans is composed of 195 amino-acid residues with a molecular mass of 22 378
      Da. Crystals were obtained by the sitting-drop vapour-diffusion method and
      diffracted to 2.05 A resolution. FadR was crystallized at 296 K using
      polyethylene glycol 3350 as a precipitant. The crystal belonged to the apparent
      trigonal space group P3(2)21, with unit-cell parameters a = b = 56.34, c = 199.73
      A. The Matthews coefficient and solvent content were estimated to be 2.0 A(3) Da(
      1) and 39.8%, respectively, assuming that the asymmetric unit contained two
      molecules of FadR, which was subsequently confirmed by molecular-replacement
      calculations.

PMID- 22869137
TI  - Preliminary crystallographic analysis of glyceraldehyde-3-phosphate dehydrogenase
      3 from Saccharomyces cerevisiae.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an important enzyme in the
      glycolytic pathway. In addition to its conventional metabolic role, GAPDH has
      been identified to possess diverse cellular functions. In this study,
      glyceraldehyde-3-phosphate dehydrogenase 3, the third isoform of GAPDH from
      Saccharomyces cerevisiae, was cloned, expressed, purified and crystallized. The
      crystals belonged to space group I4(1)22, with unit-cell parameters a = b =
      116.13, c = 119.21 A. X-ray diffraction data were collected to a resolution of
      2.6 A. The structure was solved by molecular replacement and refinement is in
      progress.

PMID- 22869138
TI  - Structure determination by multiple-wavelength anomalous dispersion (MAD) at the
      Pr LIII edge.
AB  - The use of longer X-ray wavelengths in macromolecular crystallography has grown
      significantly over the past few years. The main reason for this increased use of
      longer wavelengths has been to utilize the anomalous signal from sulfur,
      providing a means for the experimental phasing of native proteins. Here, another
      possible application of longer X-ray wavelengths is presented: MAD at the L(III)
      edges of various lanthanide compounds. A first experiment at the L(III) edge of
      Pr was conducted on HZB MX beamline BL14.2 and resulted in the successful
      structure determination of the C-terminal domain of a spliceosomal protein. This
      experiment demonstrates that L(III) edges of lanthanides constitute potentially
      attractive targets for long-wavelength MAD experiments.

PMID- 22869139
TI  - Crystallization of Pseudomonas aeruginosa AmrZ protein: development of a
      comprehensive method for obtaining and optimization of protein-DNA crystals.
AB  - The AmrZ protein from the pathogenic bacterium Pseudomonas aeruginosa is a
      transcription factor that activates and represses the genes for several potent
      virulence factors, which gives the bacteria a selective advantage in infection.
      AmrZ was crystallized in complex with DNA containing the amrZ1 repressor binding
      site. Obtaining crystals of the complex required the integration of a number of
      well known techniques along with the development of new methods. Here, these
      processes are organized and combined into a comprehensive method which yielded
      diffraction-quality crystals. Part of this method included thorough data mining
      of the crystallization conditions of protein-DNA complexes to create a new
      directed crystallization screen. An optimized technique for the verification of
      protein-DNA complexes in crystals is also presented. Taken together, the methods
      described in this article attempt to streamline the difficult process of
      obtaining diffraction-quality crystals of protein-DNA complexes through the
      organization of older methods combined with the introduction of new techniques.

PMID- 22869140
TI  - Single-drop optimization of protein crystallization.
AB  - A completely new crystal-growth device has been developed that permits charting a
      course across the phase diagram to produce crystalline samples optimized for
      diffraction experiments. The utility of the device is demonstrated for the
      production of crystals for the traditional X-ray diffraction data-collection
      experiment, of microcrystals optimal for data-collection experiments at a modern
      microbeam insertion-device synchrotron beamline and of nanocrystals required for
      data collection on an X-ray laser beamline.

PMID- 22869142
TI  - Snail1 controls TGF-beta responsiveness and differentiation of mesenchymal stem
      cells.
AB  - The Snail1 transcriptional repressor plays a key role in triggering epithelial-to
      mesenchymal transition. Although Snail1 is widely expressed in early development,
      in adult animals it is limited to a subset of mesenchymal cells where it has a
      largely unknown function. Using a mouse model with inducible depletion of Snail1,
      here we demonstrate that Snail1 is required to maintain mesenchymal stem cells
      (MSCs). This effect is associated to the responsiveness to transforming growth
      factor (TGF)-beta1 that shows a strong Snail1 dependence. Snail1 depletion in
      conditional knockout adult animals causes a significant decrease in the number of
      bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely
      differentiate to osteoblasts or adipocytes and, in contrast to controls, are
      resistant to the TGF-beta1-induced differentiation block. These results
      demonstrate a new role for Snail1 in TGF-beta response and MSC maintenance. 

PMID- 22869143
TI  - BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2
      interaction.
AB  - Promyelocytic leukemia protein (PML) modulates the p53 tumor suppressor through
      its interaction with p53 and MDM2. We found that activated big MAP kinase 1
      (BMK1) preferentially associates with PML isoform IV and disrupts PML-MDM2
      interaction. Doxorubicin, a common chemotherapeutic agent, is known to promote
      PML-mediated p53 activation in part by promoting PML-dependent MDM2 nucleolar
      sequestration. We discovered that BMK1 deactivation coupled with doxorubicin
      synergistically enhanced MDM2 nucleolar sequestration and, consequently, promoted
      PML-mediated p53 upregulation leading to tumor cell apoptosis in vitro and tumor
      regression in vivo. Collectively, these results not only suggest that BMK1
      activity has a role in suppressing p53 by blocking the interaction between PML
      and MDM2, but also implicate that pharmacological BMK1 inhibitor should
      significantly enhance the anticancer capacity of doxorubicin-based chemotherapy. 

PMID- 22869145
TI  - Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and
      NF-kappaB signaling that promotes colon cancer progression.
AB  - L1, a neuronal cell adhesion receptor of the immunoglobulin-like protein family
      is expressed in invading colorectal cancer (CRC) cells as a target gene of
      Wnt/beta-catenin signaling. Overexpression of L1 in CRC cells enhances cell
      motility and proliferation, and confers liver metastasis. We recently identified
      ezrin and the IkappaB-NF-kappaB pathway as essential for the biological
      properties conferred by L1 in CRC cells. Here, we studied the underlying
      molecular mechanisms and found that L1 enhances ezrin phosphorylation, via Rho
      associated protein kinase (ROCK), and is required for L1-ezrin co-localization at
      the juxtamembrane domain and for enhancing cell motility. Global transcriptomes
      from L1-expressing CRC cells were compared with transcriptomes from the same
      cells expressing small hairpin RNA (shRNA) to ezrin. Among the genes whose
      expression was elevated by L1 and ezrin we identified insulin-like growth factor
      binding protein 2 (IGFBP-2) and showed that its increased expression is mediated
      by an NF-kappaB-mediated transactivation of the IGFBP-2 gene promoter. Expression
      of a constitutively activated mutant ezrin (Ezrin567D) could also increase IGFBP
      2 levels in CRC cells. Overexpression of IGFBP-2 in CRC cells lacking L1-enhanced
      cell proliferation (in the absence of serum), cell motility, tumorigenesis and
      induced liver metastasis, similar to L1 overexpression. Suppression of endogenous
      IGFBP-2 in L1-transfected cells inhibited these properties conferred by L1. We
      detected IGFBP-2 in a unique organization at the bottom of human colonic crypts
      in normal mucosa and at increased levels throughout human CRC tissue samples co
      localizing with the phosphorylated p65 subunit of NF-kappaB. Finally, we found
      that IGFBP-2 and L1 can form a molecular complex suggesting that L1-mediated
      signaling by the L1-ezrin-NF-kappaB pathway, that induces IGFBP-2 expression, has
      an important role in CRC progression. 

PMID- 22869144
TI  - Stabilization of HIF-2alpha through redox regulation of mTORC2 activation and
      initiation of mRNA translation.
AB  - Hypoxia inducible factor-2alpha (HIF-2alpha) has a critical role in renal
      tumorigenesis. HIF-2alpha is stabilized in von Hippel-Lindau (VHL)-deficient
      renal cell carcinoma through mechanisms that require ongoing mRNA translation.
      Mammalian target of rapamycin (mTOR) functions in two distinct complexes: Raptor
      associated mTORC1 and Rictor-associated mTORC2. Rictor-associated mTORC2 complex
      has been linked to maintaining HIF-2alpha protein in the absence of VHL; however,
      the mechanisms remain to be elucidated. Although Raptor-associated mTORC1 is a
      known key upstream regulator of mRNA translation, initiation and elongation, the
      role of mTORC2 in regulating mRNA translation is not clear. Complex assembly of
      the mRNA cap protein, eukaryotic translation initiation factor 4 (eIF4)E, with
      activators (eIF4 gamma (eIF4G)) and inhibitors (eIF4E-binding protein 1 (4E-BP1))
      are rate-limiting determinants of mRNA translation. Our laboratory has previously
      demonstrated that reactive oxygen species, mediated by p22(phox)-based Nox
      oxidases, are enhanced in VHL-deficient cells and have a role in the activation
      of Akt on S473, a site phosphorylated by the mTORC2 complex. In this study, we
      examined the role of Rictor-dependent regulation of HIF-2alpha through eIF4E
      dependent mRNA translation and examined the effects of p22(phox)-based Nox
      oxidases on TORC2 regulation. We demonstrate for the first time that mTORC2
      complex stability and activation is redox sensitive, and further defined a novel
      role for p22(phox)-based Nox oxidases in eIF4E-dependent mRNA translation through
      mTORC2. Furthermore, we provide the first evidence that silencing of p22(phox)
      reduces HIF-2alpha-dependent gene targeting in vitro and tumor formation in vivo.
      The clinical relevance of these studies is demonstrated. 

PMID- 22869146
TI  - Epigenetic-induced repression of microRNA-205 is associated with MED1 activation
      and a poorer prognosis in localized prostate cancer.
AB  - Deregulation of microRNA (miRNA) expression can have a critical role in
      carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205)
      transcription is commonly repressed and the MIR-205 locus is hypermethylated.
      LOC642587, the MIR-205 host gene of unknown function, is also concordantly
      inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220
      and PPARBP) for transcriptional silencing in normal prostate cells, leading to
      reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein.
      Overexpression of miR-205 in prostate cancer cells negatively affects cell
      viability, consistent with a tumor suppressor function. We found that
      hypermethylation of the MIR-205 locus was strongly related with a decrease in miR
      205 expression and an increase in MED1 expression in primary tumor samples
      (n=14), when compared with matched normal prostate (n=7). An expanded patient
      cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA
      methylation in tumors compared with normal, and MIR-205 hypermethylation is
      significantly associated with biochemical recurrence (hazard ratio=2.005, 95%
      confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative
      prostate specific antigen. In summary, these results suggest that miR-205 is an
      epigenetically regulated tumor suppressor that targets MED1 and may provide a
      potential biomarker in prostate cancer management.

PMID- 22869147
TI  - Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic
      leukemia.
AB  - Glucocorticoids (GCs) are among the most widely prescribed medications in
      clinical practice. The beneficial effects of GCs in acute lymphoblastic leukemia
      (ALL) are based on their ability to induce apoptosis, but the underlying
      transcriptional mechanisms remain poorly defined. Computational modeling has
      enormous potential in the understanding of biological processes such as apoptosis
      and the discovery of novel regulatory mechanisms. We here present an integrated
      analysis of gene expression kinetic profiles using microarrays from GC sensitive
      and resistant ALL cell lines and patients, including newly generated and
      previously published data sets available from the Gene Expression Omnibus. By
      applying time-series clustering analysis in the sensitive ALL CEM-C7-14 cells, we
      identified 358 differentially regulated genes that we classified into 15 kinetic
      profiles. We identified GC response element (GRE) sequences in 33 of the
      upregulated known or potential GC receptor (GR) targets. Comparative study of
      sensitive and resistant ALL showed distinct gene expression patterns and
      indicated unexpected similarities between sensitivity-restored and resistant ALL.
      We found that activator protein 1 (AP-1), Ets related gene (Erg) and GR pathways
      were differentially regulated in sensitive and resistant ALL. Erg protein levels
      were substantially higher in CEM-C1-15-resistant cells, c-Jun was significantly
      induced in sensitive cells, whereas c-Fos was expressed at low levels in both. c
      Jun was recruited on the AP-1 site on the Bim promoter, whereas a transient Erg
      occupancy on the GR promoter was detected. Inhibition of Erg and activation of GR
      lead to increased apoptosis in both sensitive and resistant ALL. These novel
      findings significantly advance our understanding of GC sensitivity and can be
      used to improve therapy of leukemia.

PMID- 22869149
TI  - LMTK3 is implicated in endocrine resistance via multiple signaling pathways.
AB  - Resistance to endocrine therapy in breast cancer is common. With the aim of
      discovering new molecular targets for breast cancer therapy, we have recently
      identified LMTK3 as a regulator of the estrogen receptor-alpha (ERalpha) and
      wished to understand its role in endocrine resistance. We find that inhibition of
      LMTK3 in a xenograft tamoxifen (Tam)-resistant (BT474) breast cancer mouse model
      results in re-sensitization to Tam as demonstrated by a reduction in tumor
      volume. A whole genome microarray analysis, using a BT474 cell line, reveals
      genes significantly modulated (positively or negatively) after LMTK3 silencing,
      including some that are known to be implicated in Tam resistance, notably c-MYC,
      HSPB8 and SIAH2. We show that LMTK3 is able to increase the levels of HSPB8 at a
      transcriptional and translational level thereby protecting MCF7 cells from Tam
      induced cell death, by reducing autophagy. Finally, high LMTK3 levels at baseline
      in tumors are predictive for endocrine resistance; therapy does not lead to
      alteration in levels, whereas in patient's plasma samples, acquired LMTK3 gene
      amplification (copy number variation) was associated with relapse while receiving
      Tam. In aggregate, these data support a role for LMTK3 in both innate (intrinsic)
      and acquired (adaptive) endocrine resistance in breast cancer. 

PMID- 22869148
TI  - Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase
      inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of
      acquired resistance.
AB  - Fibroblast growth factor receptors (FGFRs) can act as driving oncoproteins in
      certain cancers, making them attractive drug targets. Here we have characterized
      tumour cell responses to two new inhibitors of FGFR1-3, AZ12908010 and the
      clinical candidate AZD4547, making comparisons with the well-characterized FGFR
      inhibitor PD173074. In a panel of 16 human tumour cell lines, the anti
      proliferative activity of AZ12908010 or AZD4547 was strongly linked to the
      presence of deregulated FGFR signalling, indicating that addiction to deregulated
      FGFRs provides a therapeutic opportunity for selective intervention. Acquired
      resistance to targeted tyrosine kinase inhibitors is a growing problem in the
      clinic but has not yet been explored for FGFR inhibitors. To assess how FGFR
      dependent tumour cells adapt to long-term FGFR inhibition, we generated a
      derivative of the KMS-11 myeloma cell line (FGFR(Y373C)) with acquired resistance
      to AZ12908010 (KMS-11R cells). Basal phosphorylated FGFR and FGFR-dependent
      downstream signalling were constitutively elevated and refractory to drug in KMS
      11R cells. Sequencing of FGFR3 in KMS-11R cells revealed the presence of a
      heterozygous mutation at the gatekeeper residue, encoding FGFR3(V555M);
      consistent with this, KMS-11R cells were cross-resistant to AZD4547 and PD173074.
      These results define the selectivity and efficacy of two new FGFR inhibitors and
      identify a secondary gatekeeper mutation as a mechanism of acquired resistance to
      FGFR inhibitors that should be anticipated as clinical evaluation proceeds.

PMID- 22869150
TI  - Central roles of apoptotic proteins in mitochondrial function.
AB  - Mitochondria have been classically characterized as organelles with
      responsibility for cellular energy production in the form of ATP, but they are
      also the organelles through which apoptotic signaling occurs. Cell stress stimuli
      can result in outer membrane permeabilization, after which mitochondria release
      numerous proteins involved in apoptotic signaling, including cytochrome c,
      apoptosis-inducing factor, endonuclease G, Smac/DIABLO and Omi/HtrA2. Cell fate
      is determined by signaling through apoptotic proteins within the Bcl-2 (B-cell
      lymphoma 2) protein family, which converges on mitochondria. Many cancerous cells
      display abnormal levels of Bcl-2 protein family member expression that results in
      defective apoptotic signaling. Alterations in bioenergetic function also
      contribute to cancer as well as numerous other disorders. Recent evidence
      indicates that several pro-apoptotic proteins localized within mitochondria, as
      well as proteins within the Bcl-2 protein family, can influence mitochondrial
      bioenergetic function. This review focuses on the emerging roles of these
      proteins in the control of mitochondrial activity.

PMID- 22869151
TI  - JAK/STAT signaling in hematological malignancies.
AB  - The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)
      pathway is central to signaling by cytokine receptors, a superfamily of more than
      30 transmembrane proteins that recognize specific cytokines, and is critical in
      blood formation and immune response. Many of those receptors transmit anti
      apoptotic, proliferative and differentiation signals, and their expression and
      functions are critical for the formation of blood lineages. Several cancers,
      including blood malignancies, have been associated with constitutive activation
      of members of the STAT family, which normally require JAK-mediated tyrosine
      phosphorylation for transcriptional activation. More recently, human
      myeloproliferative neoplasms were discovered to be associated with a unique
      acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or
      thrombopoietin receptor mutations that constitutively activate wild-type JAK2.
      Prompted by these observations, many studies have explored the possibility that
      JAKs, cytokine receptors, or other components of the JAK/STAT pathway are mutated
      or upregulated in several hematological malignancies. This has been observed in
      certain pediatric acute lymphoblastic leukemias and adult T-cell lymphoblastic
      leukemias, and overexpression of JAK2 seems to be important in Hodgkin lymphoma.
      Here we discuss the nature and respective contribution of mutations dysregulating
      the JAK/STAT pathway in hematological malignancies and present examples in which
      such mutations drive the disease, contribute to the phenotype, or provide a
      survival and proliferative advantage. JAK inhibitors are making their way into
      the therapeutic arsenal (for example, in myelofibrosis), and we discuss the
      possibility that other hematological diseases might benefit from treatment with
      these inhibitors in combination with other agents.

PMID- 22869152
TI  - Flotillins as regulators of ErbB2 levels in breast cancer.
AB  - Amplification and overexpression of the receptor tyrosine kinase ErbB2 occur in
      up to 30% of human breast cancers, and high ErbB2 levels are correlated with poor
      prognosis for breast cancer patients. In contrast to the epithelial growth factor
      receptor (ErbB1), ErbB2 is not downregulated by ligand-induced mechanisms. Here
      we show that flotillins are involved in the stabilization of ErbB2 at the plasma
      membrane. In SKBR3 breast cancer cells and breast cancer tissue, a positive
      correlation between flotillin and ErbB2 expression levels could be demonstrated.
      Moreover, the tissue microarray analyses of biopsies from 194 patients diagnosed
      with carcinomas of the breast showed that flotillin-2 emerged as a potential
      predictor of prognosis in breast cancer. Depletion of flotillin-1 and flotillin-2
      leads to internalization and degradation of ErbB2. Furthermore, flotillin-1 and 
      2 were found to be in a molecular complex with ErbB2 and Hsp90. The depletion of
      one of these proteins results in disruption of this complex, followed by
      destabilization of ErbB2 at the membrane, and its internalization and
      degradation. As a consequence, ErbB2-triggered downstream signalling is
      inhibited. Our data demonstrate a novel mechanism for interfering with ErbB2
      signalling, which potentially can have clinical impact. 

PMID- 22869153
TI  - Reprogramming cancer cells: back to the future.
AB  - Reprogramming healthy somatic cells into induced pluripotent stem cells (iPSCs)
      with four defined factors (Oct4, Sox2, c-Myc and Klf4) has been intensively
      investigated. However, reprogramming diseased cells such as cancer cells has
      fallen much behind. In this issue of Oncogene, Zhang et al. demonstrated that
      reprogrammed sarcoma cells with defined factors, as well as Nanog and Lin28, lost
      their tumorigenicity and dedifferentiated to mesenchymal stem cells (MSC) and
      hematopoietic stem cell (HSC)-like cells that can be terminally differentiated
      into mature connective tissues and red blood cells, suggesting sarcoma cells may
      be reversed back to a stage of common ancestor iPSC bifurcating for HSC and MSC
      ontogeny. It may, therefore, provide a novel strategy for cancer treatment via
      ancestor pluripotency induction.

PMID- 22869154
TI  - Harnessing the immunomodulatory and tissue repair properties of mesenchymal stem
      cells to restore beta cell function.
AB  - Islet cell transplantation has therapeutic potential to cure type 1 diabetes
      (T1D), which is characterized by autoimmune-mediated destruction of insulin
      producing beta cells. However, current success rates are limited by long-term
      decline in islet graft function resulting partially from poor revascularization
      and immune destruction. Mesenchymal stem cells (MSCs) have the potential to
      enhance islet transplantation and prevent disease progression by a multifaceted
      approach. MSCs have been shown to be effective at inhibiting inflammatory
      mediated immune responses and at promoting tissue regeneration. The
      immunomodulatory and tissue repairing properties of MSCs may benefit beta cell
      regeneration in the context of T1D. This review will elucidate how MSCs can
      minimize beta cell damage by providing survival signals and simultaneously
      modulate the immune response by inhibiting activation, and proliferation of
      several immune cell types. In addition, MSCs can enhance islet graft
      revascularization, maintaining long-term beta cell viability and function.

PMID- 22869156
TI  - Recurrence of gallstones after cholecystectomy is associated with ABCG5/8
      genotype.
AB  - BACKGROUND: Gallstone disease is a frequent and economically highly relevant
      disorder, with cholecystectomy representing one of the most frequently performed
      operations world-wide. Gallstone recurrence after cholecystectomy is associated
      with complications such as biliary sepsis and pancreatitis. As yet, variant ABCG8
      D19H is the most widely recognized genetic risk factor for gallstone disease. The
      aim of the study is to investigate whether ABCG8-D19H is associated with
      gallstone recurrence after cholecystectomy. METHODS: Two thousand three hundred
      and eight patients from an earlier study of gallstone risk factors were re
      contacted by mail, leading to 1,915 patients with available clinical and genetic
      information. Symptomatic gallstone recurrence was established if it occurred more
      than six months after surgery. Median follow-up time after cholecystectomy was
      eight years. RESULTS: Gallstones recurred in 37 patients (1.9%). ABCG-D19H was
      found to be significantly associated with gallstone recurrence (p = 0.034). The
      allelic odds ratio was 1.97 (95% CI 1.12-infinity). In a multivariate logistic
      regression analysis adjusted for age, sex, BMI and type of surgery, ABCG8-D19H
      remained a significant predictor, both in the total cohort (p = 0.024) and in the
      subgroup for whom information on type and scheduling of surgery was available (N
      = 1,650, p = 0.020). CONCLUSIONS: ABCG8-D19H is a predictor of gallstone
      recurrence, a major long term postoperative biliary complication. Moreover, the
      observed association also reemphasizes the importance of the sterolin transporter
      for stone formation.

PMID- 22869157
TI  - The impact of patatin-like phospholipase domain-containing protein 3 polymorphism
      on hepatocellular carcinoma prognosis.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) rs738409 in patatin-like
      phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat
      accumulation and disease progression in patients with non-alcoholic fatty liver
      disease and alcoholic liver disease (ALD). This study was conducted to determine
      whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular
      carcinoma (HCC) in patients with various liver diseases. METHODS: We enrolled 638
      consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72
      patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104
      with non-B non-C (NBNC). RESULTS: NBNC patients exhibited large tumors of
      advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than
      HBV or HCV patients (P < 0.001 and <0.001, respectively; log-rank test). The G/G
      genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC
      patients (P < 0.001) and was significantly associated with higher body mass index
      (BMI) and an increased aspartate aminotransferase to platelet ratio index. No
      significant differences were observed in survival with differences in PNPLA3 SNP
      genotypes among the patients, although ALD patients with the G/G genotype of
      PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI
      (P = 0.028). CONCLUSIONS: The G/G genotype of PNPLA3 rs738409 SNP was more
      frequently distributed, and associated with BMI and fibrosis among NBNC-HCC
      patients but not among HBV or HCV patients. These genotypes might affect HCC
      prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients.

PMID- 22869158
TI  - Efficacy of Er,Cr:YSGG laser with endodontical radial firing tips on the outcome
      of endodontic treatment: blind randomized controlled clinical trial with six
      month evaluation.
AB  - Clinical reports stating the efficacy of novel root canal disinfection protocols
      are an important focus in endodontic research. This blind randomized clinical
      trial assessed the clinical efficacy of the erbium, chromium:yttrium-scandium
      gallium-garnet (Er,Cr:YSGG) laser radial firing tips (RFT) versus the concomitant
      use of 3 % sodium hypochlorite and interim calcium hydroxide paste in necrotic
      teeth with chronic apical periodontitis. We hypothesized to find similar or
      improved bone healing in the laser-assisted endodontic treatment. Thirty-six
      anterior and premolar teeth were randomly assigned. In group 1, teeth were
      prepared with 3 % sodium hypochlorite for irrigation and calcium hydroxide as
      inter-appointment dressing; in group 2, teeth were prepared with saline solution
      and irradiated with Er,Cr:YSGG laser using RFT2 (140 MUs, 37.5 mJ, 20 Hz) and
      RFT3 (140 MUs, 62.5 mJ, 20 Hz) in the first and second appointment, respectively,
      four times each, moving at 2 mm s(-1) from apical to coronal. The primary outcome
      measure was changed in apical bone density at 6 months, using the periapical
      index (PAI) for blind radiographic evaluation. Twenty-nine patients were examined
      and subjected to statistical analysis, 12 in group 1 and 17 in group 2. There was
      one treatment failure in group 1. Both groups gave similar outcomes exhibiting
      statistically significant decreases in PAI scores. 

PMID- 22869160
TI  - Encrustation of urologic double pigtail catheters-an ex vivo optical coherence
      tomography (OCT) study.
AB  - This study aims to evaluate whether optical coherence tomography (OCT) using both
      the surface and the endoluminal technique is feasible to investigate the
      locations and degree of encrustation process in clinically used ureteral stents.
      After removal from patients, 14 polyurethane JJ stents were investigated. A fresh
      JJ served as a control. The external surfaces were examined using an endoscopic
      surface OCT whereas the intraluminal surfaces were investigated by an endoluminal
      radial OCT device. The focus was on detection of encrustation or crystalline
      sedimentation. In 12 female and two male patients, the median indwelling time of
      the ureteral catheter was 100 days (range, 19-217). Using the endoluminal OCT,
      the size and grade of intraluminal encrustation could be expressed as a
      percentage relating to the open lumen of the reference stent. The maximum
      encrustation observed resulted in a remaining unrestricted lumen of 15-35 %
      compared to the reference. The luminal reduction caused by encrustation was
      significantly higher at the proximal end of the ureteral stent as compared to its
      distal part. The extraluminal OCT investigations facilitated the characterization
      of extraluminal encrustation. OCT techniques were feasible and facilitated the
      detection of encrustation of double pigtail catheters on both the extra and intra
      luminal surface. Quantitative expression of the degree of intraluminal
      encrustation could be achieved, with the most dense and thickened occurrence of
      intraluminal incrustation in the upper curl of the JJ stent.

PMID- 22869159
TI  - Laser irradiation affects enzymatic antioxidant system of streptozotocin-induced
      diabetic rats.
AB  - The aim of the present study was to analyze the effect of low-power laser
      irradiation in the antioxidant enzymatic system of submandibular (SMG) and
      parotid (PG) salivary glands of streptozotocin-induced diabetic rats. The animals
      were randomly divided into six groups: three diabetic groups (D0, D5, and D20)
      and three non-diabetic groups (C0, C5, and C20), according to laser dose received
      (0, 5, and 20 J/cm(2), respectively). Areas of approximately 1 cm(2) were
      demarcated in the salivary glands (each parotid and both submandibular glands)
      and after irradiated according to Simoes et.al. (Lasers Med Sci 24:202-208,
      2009). A diode laser (660 nm/100 mW) was used, with laser beam spot of 0.0177
      cm(2). The group treated with 5 J/cm(2) laser dose was subjected to irradiation
      for 1 min and 4 s (total irradiation time) and the group treated with 20 J/cm(2)
      laser dose was subjected to irradiation for 4 min and 16 s. Twenty-four hours
      after irradiation the animals were euthanized and the salivary glands were
      removed for biochemical analysis. The total antioxidant values (TA), the activity
      of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase enzymes
      were determined. SOD and CAT activities, as well as TA were higher in SMG of
      irradiated diabetic rats. However, in SMG of non-diabetic rats, laser irradiation
      decreased TA values and led to an increase in the CAT activity. In addition,
      there was a decrease in the activity of CAT in PG of diabetic and non-diabetic
      animals after laser irradiation. According to the results of the present study,
      low-power laser irradiation can affect the enzymatic antioxidant system of
      salivary glands of streptozotocin-induced diabetic rats.

PMID- 22869161
TI  - N-substituted 5-chloro-6-phenylpyridazin-3(2H)-ones: synthesis, insecticidal
      activity against Plutella xylostella (L.) and SAR study.
AB  - A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H)-one derivatives were
      synthesized based on our previous work; all compounds were characterized by
      spectral data and tested for in vitro insecticidal activity against Plutella
      xylostella. The results showed that the synthesized pyridazin-3(2H)-one compounds
      possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h
      which showed > 90% activity at 100 mg/L. The structure-activity relationships
      (SAR) for these compounds were also discussed.

PMID- 22869155
TI  - Comprehensive search for Alzheimer disease susceptibility loci in the APOE
      region.
AB  - OBJECTIVE: To evaluate the association of risk and age at onset (AAO) of
      Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the
      chromosome 19 region including apolipoprotein E (APOE) and a repeat-length
      polymorphism in TOMM40 (poly-T, rs10524523). DESIGN: Conditional logistic
      regression models and survival analysis. SETTING: Fifteen genome-wide association
      study data sets assembled by the Alzheimer's Disease Genetics Consortium.
      PARTICIPANTS: Eleven thousand eight hundred forty AD cases and 10 931 cognitively
      normal elderly controls. MAIN OUTCOME MEASURES: Association of AD risk and AAO
      with genotyped and imputed SNPs located in an 800-Mb region including APOE in the
      entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly
      T marker genotyped in a subset of 1256 cases and 1605 controls. RESULTS: In
      models adjusting for APOE epsilon4, no SNPs in the entire region were
      significantly associated with AAO at P.001. Rs10524523 was not significantly
      associated with AD or AAO in models adjusting for APOE genotype or within the
      subset of epsilon3/epsilon3 subjects. CONCLUSIONS: APOE alleles epsilon2,
      epsilon3, and epsilon4 account for essentially all the inherited risk of AD
      associated with this region. Other variants including a poly-T track in TOMM40
      are not independent risk or AAO loci.

PMID- 22869162
TI  - A new natural lactone from Dimocarpus longan Lour. seeds.
AB  - A new natural product named longanlactone was isolated from Dimocarpus longan
      Lour. seeds. Its structure was determined as 3-(2-acetyl-1H--pyrrol-1-yl)-5-(prop
      2-yn-1-yl)dihydrofuran-2(3H)-one by spectroscopic methods and HRESIMS.

PMID- 22869164
TI  - Radix grafts in cosmetic rhinoplasty: lessons from an 8-year review.
AB  - We describe our experience with radix augmentation during cosmetic rhinoplasty
      over an 8-year period using both autologous and synthetic grafts and provide
      insight into maximizing success. We discuss various surgical considerations,
      including patient selection, graft materials, and dealing with complications. We
      focus on our operative technique and provide patient examples.

PMID- 22869165
TI  - Sensing immune responses with customized peptide microarrays.
AB  - The intent to solve biological and biomedical questions in high-throughput led to
      an immense interest in microarray technologies. Nowadays, DNA microarrays are
      routinely used to screen for oligonucleotide interactions within a large variety
      of potential interaction partners. To study interactions on the protein level
      with the same efficiency, protein and peptide microarrays offer similar
      advantages, but their production is more demanding. A new technology to produce
      peptide microarrays with a laser printer provides access to affordable and highly
      complex peptide microarrays. Such a peptide microarray can contain up to 775
      peptide spots per cm2, whereby the position of each peptide spot and, thus, the
      amino acid sequence of the corresponding peptide, is exactly known. Compared to
      other techniques, such as the SPOT synthesis, more features per cm2 at lower
      costs can be synthesized which paves the way for laser printed peptide
      microarrays to take on roles as efficient and affordable biomedical sensors.
      Here, we describe the laser printer-based synthesis of peptide microarrays and
      focus on an application involving the blood sera of tetanus immunized
      individuals, indicating the potential of peptide arrays to sense immune
      responses.

PMID- 22869163
TI  - The proboscis extension reflex to evaluate learning and memory in honeybees (Apis
      mellifera): some caveats.
AB  - The proboscis extension reflex (PER) is widely used in a classical conditioning
      (Pavlovian) context to evaluate learning and memory of a variety of insect
      species. The literature is particularly prodigious for honeybees (Apis mellifera)
      with more than a thousand publications. Imagination appears to be the only limit
      to the types of challenges to which researchers subject honeybees, including all
      the sensory modalities and a broad diversity of environmental treatments.
      Accordingly, some remarkable insights have been achieved using PER. However,
      there are several challenges to evaluating the PER literature that warrant a
      careful and thorough review. We assess here variation in methods that makes
      interpretation of studies, even those researching the same question, tenuous. We
      suggest that the numerous variables that might influence experimental outcomes
      from PER be thoroughly detailed by researchers. Moreover, the influence of
      individual variables on results needs to carefully evaluated, as well as among
      two or more variables. Our intent is to encourage investigation of the influence
      of numerous variables on PER results.

PMID- 22869166
TI  - The fat of the matter.

PMID- 22869167
TI  - Point-of-care tests poised to alter course of HIV treatment.

PMID- 22869168
TI  - Race heats up for first-to-market drugs for resistant tuberculosis.

PMID- 22869169
TI  - Potential first-in-class osteoporosis drug speeds through trials.

PMID- 22869170
TI  - Study finds up to $5 billion in potential trial cost savings.

PMID- 22869171
TI  - Overactive bladder, under scrutiny, gets a new treatment.

PMID- 22869172
TI  - New tracking system proposed to help recall faulty devices.

PMID- 22869173
TI  - Clinical efficacy data on gene tests trails marketing in psychiatry.

PMID- 22869175
TI  - Straight talk with...Joe Selby.
AB  - The US Supreme Court's ruling in late June to uphold most of the Patient
      Protection and Affordable Care Act of 2010 decided more than just the fate of the
      law's individual mandate for health care. It also allowed many of the other
      provisions of the legislation to safely go ahead. Chief among those was the
      establishment of a comparative-effectiveness research hub called the Patient
      Centered Outcomes Research Institute (PCORI), located in Washington, DC. With a
      budget of $3.3 billion over the next seven years and an independent status, PCORI
      is now tasked with creating the evidence base to help patients and doctors make
      more informed decisions about their medical choices. Leading the fledgling
      institute is executive director Joe Selby. A family physician and clinical
      epidemiologist, Selby joined PCORI in July 2011 after 13 years as head of
      research at Kaiser Permanente, the California-based health provider. Even amid
      all the uncertainty that surrounded the future of US healthcare reform, Selby,
      together with PCORI's board of directors, managed to help craft the institute's
      first research agenda and to fund 50 pilot projects totaling $30 million, all in
      the spring of this year. Elie Dolgin spoke with Selby to discuss how PCORI will
      influence the debate about which treatments work best.

PMID- 22869176
TI  - Nurses on trial.

PMID- 22869177
TI  - The time for pharmaceutical compulsory licensing has expired.

PMID- 22869179
TI  - Cisplatin-induced primordial follicle oocyte killing and loss of fertility are
      not prevented by imatinib.

PMID- 22869180
TI  - Reply to: Cisplatin-induced primordial follicle oocyte killing and loss of
      fertility are not prevented by imatinib.

PMID- 22869181
TI  - TRP-ing up brain tumors.

PMID- 22869182
TI  - Nine lives for TH9s?

PMID- 22869183
TI  - The elusive source of myofibroblasts: problem solved?

PMID- 22869184
TI  - Febrile seizures and the wandering granule cell.

PMID- 22869185
TI  - Fetuin-A: the missing link in lipid-induced inflammation.

PMID- 22869186
TI  - The dark side of the oxidative force in angiogenesis.

PMID- 22869188
TI  - A complex microworld in the gut: gut microbiota and cardiovascular disease
      connectivity.

PMID- 22869189
TI  - A complex microworld in the gut: Harnessing pathogen-commensal relations.

PMID- 22869199
TI  - Inhibition of LPS-induced retinal microglia activation by naloxone does not
      prevent photoreceptor death.
AB  - Microglia-associated inflammation is closely related to the pathogenesis of
      retinal degenerative disorders. We have previously shown in vivo that naloxone
      protected photoreceptors from light-induced apoptosis possibly through inhibiting
      microglial activation. In this study, we attempted to explore the effect of
      lipopolysaccharide (LPS)-activated microglia on photoreceptor death and the
      influence of naloxone treatment using an in vitro retinal microglia and 661 W
      photoreceptor co-culture system. Immunofluorescent staining and ELISA
      measurements demonstrated that LPS activated microglia by changing the morphology
      and increasing the production of proinflammatory factors interleukin (IL)-1beta
      and tumor necrosis factor (TNF)-alpha. Flow cytometry analysis of annexin
      V/propidium iodide staining showed that LPS-activated microglia promoted the
      apoptosis of co-cultured 661 W photoreceptor cells. Naloxone inhibited microglial
      activation and decreased the release of IL-1beta and TNF-alpha but could not
      prevent photoreceptors from undergoing apoptosis. Considering the dual role of
      microglia-associated inflammation in both neurotoxicity and neuroprotection,
      modulating the function, rather than simply inhibiting their activation, might be
      a new therapeutic method for preventing photoreceptor degeneration.

PMID- 22869198
TI  - Epigenetic mechanisms in neurological disease.
AB  - The exploration of brain epigenomes, which consist of various types of DNA
      methylation and covalent histone modifications, is providing new and
      unprecedented insights into the mechanisms of neural development, neurological
      disease and aging. Traditionally, chromatin defects in the brain were considered
      static lesions of early development that occurred in the context of rare genetic
      syndromes, but it is now clear that mutations and maladaptations of the
      epigenetic machinery cover a much wider continuum that includes adult-onset
      neurodegenerative disease. Here, we describe how recent advances in
      neuroepigenetics have contributed to an improved mechanistic understanding of
      developmental and degenerative brain disorders, and we discuss how they could
      influence the development of future therapies for these conditions.

PMID- 22869201
TI  - [Development of the Work Limitations Questionnaire Japanese version (WLQ-J):
      fundamental examination of the reliability and validity of the WLQ-J].
AB  - OBJECTIVE: It is reported that presenteeism costs more than absenteeism. However,
      it is difficult to measure presenteeism in Japan because there are few available
      instruments. We examined the reliability and validity of the Japanese version of
      the Work limitations Questionnaire (the WLQ-J). METHODS: We conducted an internet
      survey with the WLQ-J and Brief Job Stress Questionnaire (BJSQ) of 1,545 males
      and females working for an IT company and a medical institution (21-61 years of
      age). The number of employees of the IT company and nursing staff of the medical
      institution included in the analysis were 373 and 337, respectively (effective
      response rate: 46.0 %). RESULTS: The subjects' average age and the ratio of
      females were 33.2 +/- 9.5 yr old and 60.3%, respectively. Factor analysis showed
      that the number of factors and items of subscales of the WLQ-J accorded with
      those of the original WLQ. This supports the factorial validity of the WLQ-J.
      Additionally, sufficient internal consistency was recognized by Cronbach's alpha
      (the whole scale=0.97, the subscales=0.88-0.95). Criterion-related validity was
      supported by the significant dose-response relationship between the subscale
      scores of the WLQ-J and the stress response of BJSQ as an external criterion
      (p<0.01). CONCLUSIONS: The study results demonstrate the reliability and validity
      of the WLQ-J. It is expected that human resource functions such as senior
      management, personnel affairs, line management, and occupational health staff
      over a wide range of industries will use the WLQ-J. Further studies are needed to
      verify the reliability and validity of the WLQ-J by examining differences in the
      WLQ-J arising from gender, age, industry, and occupation between multiple
      studies, and by finding relationships between the WLQ-J and other evaluation
      scales.

PMID- 22869200
TI  - Optimisation of glycaemic control during episodes of severe/acute hyperglycaemia
      in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are frequently admitted
      to the hospital with severe or acute hyperglycaemia secondary to an acute illness
      or disease. Uncontrolled glycaemia is a significant problem during severe or
      acute hyperglycaemia. OBJECTIVE: This study sought to identify demographic,
      clinical, and genetic factors that may contribute to increased insulin resistance
      or worsening of glycaemic control in patients with T2DM. SETTING: This
      prospective cohort study included 156 patients with T2DM and severe or acute
      hyperglycaemia who were treated with insulin at any medical ward of the National
      University of Malaysia Medical Centre. METHOD: Insulin resistance was determined
      using the homeostatic model assessment-insulin resistance index. Glycaemic
      control during the episode of hyperglycaemia was assessed as the degree to which
      the patient achieved the target glucose levels. The polymerase chain reaction
      restriction fragment length polymorphism method was used to identify
      polymorphisms in insulin receptor substrate (IRS) genes. MAIN OUTCOME MEASURE:
      Identification of possible predictors (demographic, clinical, or genetic) for
      insulin resistance and glycaemic control during severe/acute hyperglycaemia.
      RESULTS: A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant
      predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence
      interval (CI) 1.2-16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95
      % CI 0.6-64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P
      < 0.05) may indirectly predict worsening of insulin resistance or glycaemic
      control in patients with severe/acute hyperglycaemia. CONCLUSION: Clinical and
      genetic factors contribute to worsening of insulin resistance and glycaemic
      control during severe/acute hyperglycaemia in patients with T2DM. Early
      identification of factors that may influence insulin resistance and glycaemic
      control may help to achieve optimal glycaemic control during severe/acute
      hyperglycaemia.

PMID- 22869202
TI  - [Airflow equation of a slot hood by the least square method].
AB  - OBJECTIVES: In designing a local exhaust ventilation (LEV) system, the exhaust
      airflow rate which will produce the required control velocity at the capture
      point must be predicted properly. Conventionally, the airflow requirements for
      LEV hoods have been calculated using Dalla Valle's equation. Although Dalla
      Valle's equation is a simple and convenient formula for LEV design, it is known
      that the airflow rate predicted by the equation does not always coincide with
      actual exhaust airflow rate. In order to develop a new airflow formula which can
      substitute for Dalla Valle's equation, the author aimed to develop an empirical
      airflow formula for a slot type exhaust hood using the least square method.
      METHODS: Based on the actual measurements (exhaust airflow rate, suction
      velocity, hood size and centerline distance) of test slot type hoods in several
      configurations and conditions, an empirical approximation formula which predicts
      exhaust airflow rate was developed. In this study, the approximation formula was
      described as a polynomial linear expression, and the validity of the predicted
      exhaust airflow rate by the approximation formula was confirmed by comparing with
      measured airflow rates. RESULTS: It was found that the predicted airflow rates of
      the developed approximation formula were in good agreement with the measured
      airflow rates and were more accurate than the airflow rates predicted by Dalla
      Valle's equation. CONCLUSIONS: Although the applicability of the developed
      formula is inferior to that of Dalla Valle's equation, certain economic benefits
      can be derived from the developed formula in some cases.

PMID- 22869203
TI  - [Correspondence to the radioactive material generated in the accident of
      Fukushima].

PMID- 22869204
TI  - RhoB is involved in lipopolysaccharide-induced inflammation in mouse in vivo and
      in vitro.
AB  - Small GTPase RhoB has been well documented in regulating cell adhesion, motility,
      proliferation, and survival, but to date, there is little information about the
      relationship between RhoB and inflammation. In this study, the mRNA and protein
      levels of RhoB were induced by lipopolysaccharide (LPS) in RAW264.7 cells
      determined by real-time PCR and Western blot. The upregulation of RhoB by LPS was
      also observed in mouse peritoneal macrophages and in mouse lung, liver, and
      kidney. RhoB overexpression by transfecting with wild RhoB plasmid increased the
      secretion of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) in
      RAW264.7 cells, while RhoB knockdown by RNA interference decreased the secretion
      of TNF-alpha and NO in RAW264.7 cells. TNF-alpha and NO synthase are the target
      genes of nuclear factor-kappaB (NF-kappaB), and overexpression of RhoB increased,
      whereas inhibition of RhoB decreased the basal and LPS-activated transcriptional
      activity of NF-kappaB in the cells. These results demonstrated that LPS induced
      RhoB expression in mouse in vivo and in vitro and in RAW264.7 cells, and the role
      of RhoB on LPS-induced secretion of TNF-alpha and NO was at least partly mediated
      via NF-kappaB. These results indicated that RhoB was involved in LPS-induced
      inflammation in mouse in vivo and in vitro.

PMID- 22869206
TI  - The Citizenship Project part II: impact of a citizenship intervention on clinical
      and community outcomes for persons with mental illness and criminal justice
      involvement.
AB  - This study assessed the effectiveness of an intervention based on a theoretical
      framework of citizenship on reducing psychiatric symptoms, alcohol use, and drug
      use, and increasing quality of life for persons with serious mental illness (SMI)
      and criminal justice involvement. One-hundred fourteen adults with SMI and a
      history of criminal justice involvement participated in a 2 * 3 longitudinal
      randomized controlled trial of a four-month citizenship intervention versus usual
      services. Linear mixed model analyses were used to assess the intervention's
      impact on quality of life, symptoms, and substance use. After controlling for
      baseline covariates, participants in the experimental condition reported
      significantly increased quality of life, greater satisfaction with and amount of
      activity, higher satisfaction with work, and reduced alcohol and drug use over
      time. However, individuals in the experimental condition also reported increased
      anxiety/depression and agitation at 6 months (but not 12 months) and
      significantly increased negative symptoms at 12 months. Findings suggest that
      community-oriented, citizenship interventions for persons with SMI and criminal
      justice histories may facilitate improved clinical and community outcomes in some
      domains, but some negative clinical findings suggest the need for post
      intervention support for intervention participants. Implications for practice and
      future research are discussed.

PMID- 22869207
TI  - Troubleshooting sacral neuromodulation issues.
AB  - In the past decade, the use of sacral neuromodulation has increased
      exponentially. The introduction of the tined lead, the posterior location, and
      the smaller IPG has changed the frequency and types of complications. These facts
      explain the reduction of the revision and explantation rates in the most
      contemporary series, as compared with the earlier data. Infection, pain at the
      IPG site, and reduced clinical response with or without impedance abnormalities
      are now the most frequently reported complications. Although infection should be
      managed with explantation of the entire system, device interrogation should be
      part of the physician's algorithm for managing patients with decreased sensation
      or new onset of pain, in order to check the integrity of the system. Patients who
      are not improved with new programs will most likely need surgical revision. The
      implanting physician should be aware of the ways to evaluate and manage
      complications and suboptimal responses, to appropriately troubleshoot patients,
      and to reduce the need for surgical revision.

PMID- 22869208
TI  - From the editor: transitions: a core nursing concept.

PMID- 22869205
TI  - Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of
      malignant gliomas.
AB  - Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1,
      which are potent regulators of cell growth, have been discovered in specific
      subtypes of gliomas, the most common type of primary malignant brain tumors.
      However, the frequency of these mutations in many subtypes of gliomas, and their
      association with clinical features of the patients, is poorly understood. Here we
      analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II
      III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas
      (57%), and ATRX mutations are associated with IDH1 mutations and with an
      alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred
      frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in
      astrocytomas or oligoastrocytomas ( more than 10%). This analysis allowed us to
      define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and
      IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer
      median overall survival (96 months) than patients with I-A gliomas (51 months)
      and patients with gliomas that did not harbor either signature (13 months). The
      genetic signatures distinguished clinically distinct groups of oligoastrocytoma
      patients, which usually present a diagnostic challenge, and were associated with
      differences in clinical outcome even among individual tumor types. In addition to
      providing new clues about the genetic alterations underlying gliomas, the results
      have immediate clinical implications, providing a tripartite genetic signature
      that can serve as a useful adjunct to conventional glioma classification that may
      aid in prognosis, treatment selection, and therapeutic trial design.

PMID- 22869209
TI  - Letter to the editor: situational awareness in nursing.

PMID- 22869210
TI  - Care transitions: integrating transition theory and complexity science concepts.
AB  - Care transitions, defined as hospital discharge or movement from one health care
      setting to another, are currently a major concern of health care providers and
      policy makers. Extensive empirical research has been conducted on care
      transitions, but the theoretical foundations are rarely made explicit. We propose
      that integrating concepts on complex adaptive systems from complexity science
      with classic theory on transitions in nursing provides a powerful new lens
      through which to study care transitions and improve transition outcomes. We
      summarize concepts from both theoretical approaches, propose an expanded model of
      transitions, and apply the model to the transition from hospital to home.

PMID- 22869211
TI  - Well-being in refugee women experiencing cultural transition.
AB  - This article presents a situation-specific theory of well-being in refugee women
      experiencing cultural transition. The theory resulted from 2 studies, an
      ethnography and a community-based collaborative action research project, with
      refugee women from South Sudan, who were resettled to the United States. The
      theory extends the middle-range theory of transition to include cultural
      transition as a distinct type of transition with a unique set of properties and
      conditions including 3 phases-separation, liminality, and integration. Community
      action research is discussed as a culturally relevant intervention for nurses
      working with immigrants and refugee populations to foster well-being in
      resettlement.

PMID- 22869212
TI  - The discourse of aging.
AB  - Historical and epistemological developments contribute to and reinforce the
      underlying framework that categorizes antiaging discourse and healthy aging
      discourse. This discourse creates the question "Can we live longer or better?"
      and encompasses issues of quality versus quantity, dependency versus autonomy,
      and risk versus benefit. By positing this discourse as a dichotomous tension, the
      development can be traced through the examination of select examples of
      influential studies in the field of aging. For nursing, the risk of these
      continued oppositions is potential oversimplification that may limit discernment
      of the complexities of care of older adults. Through understanding of the
      evolution and imposition of this dichotomizing discourse, nursing can provide
      older adult care within the reality of the aging experience, and develop
      frameworks, theories, and multidisciplinary discursive practice to optimize
      nursing care in the real-world spaces that exist between antiaging and healthy
      aging boundaries.

PMID- 22869213
TI  - Contentment in "Songs of the Gorilla Nation:  My Journey through Autism": A
      Humanbecoming Hermeneutic Study.
AB  - This article is an example of the use of narrative in the form of a memoir to
      explore the humanly lived experience of contentment. The humanbecoming school of
      thought provided a philosophical foundation and theoretical framework for this
      hermeneutic interpretation of Dawn Prince-Hughes' published memoir, "Songs of the
      Gorilla Nation: My Journey through Autism." The findings-contentment is enduring
      serenity unfolding with inspiring unburdening as cherished convictions arise amid
      disharmony answer the research question: what is contentment as humanly lived?
      This study enhances knowledge about contentment as quality of life.

PMID- 22869214
TI  - Acculturation and biobehavioral profiles in pregnant women of Hispanic origin:
      generational differences.
AB  - In Hispanics, acculturation may lead to negative health outcomes. This study used
      a cross-sectional design to investigate the psychosocial and biological risks in
      acculturating pregnant women of Hispanic origin (n = 470). Psychosocial risks
      depressive symptoms, anxiety, and stress-were assessed by self-report, whereas
      biological measures included stress-related and reproductive hormones. Mental
      health deteriorated across generations, with worsening depression, anxiety, and
      stress with successive generations. Stress and reproductive hormone levels
      decreased across generations, whereas body mass index and number of sexual
      partners increased. These data provide potential biobehavioral explanations of
      the relationship between acculturation and declining health among Hispanic women
      in the United States.

PMID- 22869215
TI  - Transition to fatherhood: modeling the experience of fathers of breastfed
      infants.
AB  - Transition to parenthood has long been examined from the angle of mothers'
      experience. When looked at this transition through fathers' lens, fathers'
      involvement and perceived parental efficacy appear to be landmarks of this
      experience. This article examines a model of the relationships among father
      involvement, perceived parental efficacy, events related to breastfeeding,
      support, stress, and income with a sample of 164 fathers of breastfed infants.
      This model highlights the direct and indirect contributions of support and stress
      to fathers' perceived parenting efficacy and involvement. Possible directions for
      nursing practice, education, and research are proposed to ease men's transition
      to fatherhood.

PMID- 22869216
TI  - Caregiving motivations and developmentally prompted transition for mothers of
      prematurely born infants.
AB  - Parenting transition is a process prompted by infant developmental changes and
      may be defined by motivations for caregiving and the goals they indicate.
      Qualitative exploration of neonatal and 1-year feeding experience of 22 mothers
      of very-low-birth-weight infants revealed 3 types of caregiving-related
      motivations-nurturing, relating, and shaping quality of life. The clusters of
      motivations differed between ages and across mothers, suggesting transition in
      parenting reflective of both infant development and maternal goals. Study with a
      larger sample is needed to examine change in caregiving motivations and their
      function in characterizing parenting transitions.

PMID- 22869217
TI  - Barriers and facilitators of social supports for immigrant and refugee women
      coping with postpartum depression.
AB  - An emerging concern for health care providers is how to assist immigrant and
      refugee women adapt to a new milieu and to cope with postpartum depression (PPD).
      Thirty women were interviewed to find out their perspective on what factors
      influence their help-seeking behavior and decision making about postpartum care
      and what strategies would be helpful in PPD prevention and treatment. Findings
      reveal that (a) social support networks can be supportive or nonsupportive with
      widespread effects on physical and psychological health and well-being; (b)
      cultural background and socioeconomic factors influence seeking support; (c)
      health care relationship was viewed a critical determinant to seek and accept
      help for PPD.

PMID- 22869218
TI  - Parent and youth priorities during the transition to adulthood for youth with
      special health care needs and developmental disability.
AB  - Families undertake extensive planning during transition to adulthood so youth
      with concomitant special health care needs and developmental disabilities will
      have a long-term high quality of life. Findings from an interpretive field study
      involving 64 youth and their parents indicated that the meaning of adulthood was
      functioning as independently as possible with appropriate supports. Parental
      priorities included protecting health, assuring safety and security in multiple
      realms, finding meaningful activities after high school, and establishing
      supportive social relationships. These priorities demonstrated the need to
      broaden usual health care transition goals that focus on finding adult providers
      and optimizing self-management.

PMID- 22869220
TI  - Linking the transition: a substantive theory of high-stakes clinical simulation.
AB  - Clinical simulation fosters the situational transition from student to
      professional nurse by providing students with the opportunity to care for
      simulated patients. Grounded theory was used to reveal the basic social
      psychological problem, caring as a professional nurse, and core category,
      linking, of high-stakes clinical simulation for 30 nursing students enrolled in a
      generic bachelor of science in nursing program. Linking is the 4-stage process of
      managing Sim-hype, encountering barriers, integrating-the-self, and
      interconnecting. The relationship between linking and transitions is presented
      along with implications for nursing education.

PMID- 22869219
TI  - The transition experience of developmentally impaired young adults living in a
      structured apartment setting.
AB  - The purpose of this qualitative descriptive study was to identify the lived
      experience of young adults with a history of pervasive developmental disorder and
      associated difficulties with aggressive behavior transitioning into independent
      living through a transitional apartment program. Nine men and 1 woman, aged 18 to
      24 years, were interviewed. Nine were interviewed in their apartment, and 1 was
      interviewed in an adjacent staff office. Individuals were dealing with normative
      transition issues of adolescence compounded by significant developmental and
      psychiatric impairments that tended to delay their developmental trajectories.
      Themes of poor physical health and loss were identified. The research emphasized
      the need for individually tailored transition services based on needs and level
      of disability.

PMID- 22869221
TI  - Sexual function and autonomic dysreflexia in men with spinal cord injuries: how
      should we treat?
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: Review the literature on the acute
      or prophylactic treatment of autonomic dysreflexia in the context of sexual
      activities. SETTING: International. METHODS: Medline search using AD and spinal
      cord injury and all years of publication. RESULTS: Thirty-seven papers on the
      specific treatment of AD showed that nifedipine, prazosin, captopril and
      clonidine are candidates in the context of sexual activities. Prazosin, however,
      has an initial hypotensive effect requiring to begin treatment 12 h before
      intercourse, which makes it less ideal for spontaneous sexual activities.
      Captopril has an initial hypotensive effect and was only studied in acute AD. Its
      usefulness in prophylaxis remains to be demonstrated. Clonidine has successfully
      been used clinically for decades, but never studied in randomized control trials.
      Nifedipine remains the most widely studied and significant treatment of AD
      whether in acute or prophylactic conditions. Recent concerns suggest increased
      cardiovascular risks with sublingual nifedipine in non-SCI populations, but
      negative long-term effects have not been reported in the SCI population.
      CONCLUSION: Sexual function is a priority for men with SCI. As sexual activities,
      in particular ejaculation, can be a source of AD, adequate treatments and
      prophylaxis must be considered in the context of sexual activities. Experts must
      meet and conclude on the thresholds, parameters and treatments that should be
      considered in the long-term management of AD in the context of sexual function in
      men with SCI.

PMID- 22869222
TI  - [The medical treatment of attention deficit hyperactivity disorder (ADHD) with
      amphetamines in children and adolescents].
AB  - INTRODUCTION: Psychostimulants (methylphenidate and amphetamines) are the drugs
      of first choice in the pharmacological treatment of children and adolescents with
      attention deficit hyperactivity disorder (ADHD). OBJECTIVE: We summarize the
      pharmacological characteristics of amphetamines and compare them with
      methylphenidate, special emphasis being given to a comparison of effects and side
      effects of the two substances. Finally, we analyze the abuse and addiction risks.
      METHODS: Publications were chosen based on a Medline analysis for controlled
      studies and meta-analyses published between 1980 and 2011; keywords were
      amphetamine, amphetamine salts, lisdexamphetamine, controlled studies, and
      metaanalyses. RESULTS AND DISCUSSION: Amphetamines generally exhibit some
      pharmacologic similarities with methylphenidate. However, besides inhibiting
      dopamine reuptake amphetamines also cause the release of monoamines. Moreover,
      plasma half-life is significantly prolonged. The clinical efficacy and
      tolerability of amphetamines is comparable to methylphenidate. Amphetamines can
      therefore be used if the individual response to methylphenidate or tolerability
      is insufficient before switching to a nonstimulant substance, thus improving the
      total response rate to psychostimulant treatment. Because of the high abuse
      potential of amphetamines, especially in adults, the prodrug lisdexamphetamine
      (Vyvanse) could become an effective treatment alternative. Available study data
      suggest a combination of high clinical effect size with a beneficial
      pharmacokinetic profile and a reduced abuse risk. CONCLUSIONS: In addition to
      methylphenidate, amphetamines serve as important complements in the
      psychostimulant treatment of ADHD. Future studies should focus on a differential
      comparison of the two substances with regard to their effects on different core
      symptom constellations and the presence of various comorbidities.

PMID- 22869223
TI  - [Psychotherapy and science - harmony or dissonance?].
AB  - Clinical practice and psychotherapy research are often perceived as areas of
      conflict with little common ground. Despite substantial empirical progress over
      the last few decades, research findings frequently play only a minor role in
      clinical decision making or treatment selection. Instead, clinical psychologists
      often trust their own clinical judgment, which may lead, for example, to an
      underestimation of the likelihood of treatment failures. In clinical practice,
      flexible treatments are often preferred over standardized interventions, based,
      for example, on the assumption that the latter ones will not be accepted by
      clinical patients. However, in addition to providing compelling evidence for
      their effectiveness, recent data suggest that patients highly appreciate
      standardized interventions such as structured clinical interviews. Recent
      research has shown that research-oriented training programs enhance the
      acceptance of evidence-based treatments by therapists as well as therapeutic
      outcomes. To facilitate the dissemination of research findings, psychotherapy
      researchers need to make their findings more easily accessible to practitioners,
      and training programs for clinical psychologists should be research based.

PMID- 22869224
TI  - [Assessment of temperament with the Infant Behavior Questionnaire Revised (IBQ-R)
      - the psychometric properties of a German version].
AB  - OBJECTIVE: The Infant Behavior Questionnaire Revised (IBQ-R; Gartstein &
      Rothbart, 2003) is one of the most common parent-report instruments for assessing
      infant temperament. This study evaluated the psychometric properties of a German
      version. METHOD: We studied item characteristics, internal consistency, and
      descriptive statistics for all 14 scales in a sample of 7- to 9-month-old infants
      and their mothers (N = 119). Factor analysis was conducted to identify higher
      order relationships between the scales. RESULTS: Item analysis showed mixed
      corrected item-total correlations. Internal consistencies were all moderate to
      high. Results of the factor analysis confirmed the two dimensions of
      Surgency/Extraversion and Negative Affectivity, whereas the dimension
      Orienting/Regulation was not replicated. In contrast to the American sample,
      activity level in the German sample loaded on the factor Negative Affectivity.
      The scales low intensity pleasure and soothability, which loaded on factor
      Orienting/Regulation in the original version, showed substantial loadings on both
      dimensions Surgency/Extraversion and Negative Affectivity (inverted), whereas the
      scale duration of orienting was located on the factor Surgency/Extraversion.
      CONCLUSIONS: The German version of the IBQ-R provides a satisfying instrument for
      investigating infant temperament. However, further work is needed to improve the
      methodological quality of the questionnaire. Further research should especially
      focus on the factor structure of infant temperament. We suggest developing a
      shorter version and testing it with a larger and more diverse sample.

PMID- 22869225
TI  - [Parent version of the German Children's Depression Inventory (DIKJ) -
      reliability and validity in a clinical sample].
AB  - OBJECTIVE: The psychometric properties and crossinformant agreement of the
      adapted parent version of the German Child Depression Inventory (DIKJ) were
      assessed in a clinical sample with various psychiatric diagnoses. METHOD: 129
      parents were included in the study, each with a child or adolescent (7 to 18
      years old) in outpatient psychotherapy. In 80 cases both parent and self-report
      was available. Participants filled out the DIKJ as well as the Child Behavior
      Checklist (CBCL)/Youth Self Report (YSR) at the beginning of therapy. RESULTS:
      The parent version of the DIKJ proved to be reliable as well as convergently and
      divergently valid: moderate to high correlations with the internalising sacles of
      the CBCL and low correlations with the externalising scale of the CBCL. The
      findings were similar for both parent and self-ratings. Intraclass correlations
      between parent and child ratings were moderate. DIKJ scores above the cut-off
      corresponded with the diagnostic status from the K-SADS diagnostic interview in
      59% of the self-reports and 57% of the parent reports. CONCLUSIONS: The DIKJ
      parent version shows promising reliability and validity in a clinical setting.
      The DIKJ may be used as a biperspective instrument to screen for depressive
      symptoms. However, the cut-off should be re-examined.

PMID- 22869226
TI  - [Psychoeducation leads to a reduction in fear of spiders in 8- to 9-year-old
      children - a pilot study].
AB  - OBJECTIVE: In Western societies spiders are among the least liked of all
      arthropods, eliciting feelings of fear and disgust. The clinical manifestation of
      this fear - spider phobia - is a common anxiety disorder. In most cases the
      disorder has an early onset in childhood. The symptoms show a chronic course and
      can persist into adulthood if not treated. Etiological models emphasize the role
      of modeling and negative information transmission for the acquisition of the
      disorder. Even though powerful psychotherapeutic methods exist, referral to
      treatment is rather uncommon for children. Often spontaneous remission is
      expected, but that is atypical. METHOD: The current study developed a
      psychoeducative program on spiders for elementary school children and evaluated
      it on a sample of 36 children aged 8 to 10 years. The main goal of this pilot
      study was to test the feasibility of the program. RESULTS: The study showed a
      reduction of fear of spiders after psychoeducation in girls and boys with
      previously high or moderate fear of spiders. CONCLUSIONS: The program could
      become a valuable contribution to the prevention of spider phobia and should be
      evaluated in future controlled trials.

PMID- 22869227
TI  - [Addictive internet use as a comorbid disorder among clients of an adolescent
      psychiatry - prevalence and psychopathological symptoms].
AB  - OBJECTIVES: Excessive and addictive internet use fulfilling criteria of
      nonsubstance related addiction disorder is increasingly being discussed by
      scientists and clinicians alike. Its prevalence of about 3 % among minors points
      to a relatively frequent phenomenon that can lead to functional impairment and
      distress. However, there is still no evidence concerning its prevalence among
      underaged patients in psychiatric treatment. METHODS: 81 patients between the age
      of 8 and 17 years were screened by a standardized instrument for internet
      addiction (AICA-S) to assess the prevalence of internet addiction among minors
      being treated in psychiatric inpatient settings. Their clinical symptoms were
      examined using Youth Self-Report and Child Behavior Checklist. RESULTS: 11.3 % of
      the patients fulfilled the criteria of addictive internet use. These patients
      were older and more often affected by anxiety and depression than patients
      without internet addiction. CONCLUSIONS: Data suggest that internet addiction is
      a relevant factor among minors in psychiatric institutions. Those with comorbid
      internet addiction show distinct patterns of psychopathology and may require
      disorder-specific treatment.

PMID- 22869228
TI  - [The concept of "multiple complex developmental disorder" - a disorder of social
      interaction, paranoid thinking and social anxiety in a 17-year-old boy].
AB  - OBJECTIVES: Multiple complex developmental disorder (MCDD) is a little-known
      disorder characterized by disturbances in the regulation of emotions, social
      interactions and thought disorders. Neither the classification system of ICD-10
      nor the DSM-IV lists MCDD as an independent disorder. METHODS: The study presents
      an overview on diagnostic criteria, current research and illustration by a case
      report of a 17-year-old adolescent. RESULTS: MCDD, autistic disorders and
      schizophrenic disorders partially overlap. A clear classification or
      differentiation is currently not clearly possible. CONCLUSIONS: Many open
      questions remain, and further research is needed.

PMID- 22869230
TI  - Acute unilateral hearing loss as an early symptom of lateral cerebral sinus
      venous thrombosis.
AB  - BACKGROUND: Increasing availability of neuroimaging has facilitated the diagnosis
      of cerebral sinus venous thrombosis(CSVT). However, CSVT may also present with
      unspecific or atypical symptoms, resulting in diagnostic delay.Single reports
      suggested otologic symptoms as such pitfalls. OBJECTIVE: To screen patients with
      CSVT for otologic symptoms. DESIGN: Ten-year retrospective case series. SETTING:
      Primary and tertiary care university clinic. PATIENTS: Thirty-eight patients with
      CSVT. RESULTS: Of 38 patients with CSVT, 3 individuals hadacute unilateral
      hearing loss, 2 of which also had concomitant tinnitus and headache, and were
      initially treated at the ear, nose, and throat department. Magnetic resonance
      imaging after hospital discharge showed ipsilateral thrombosis of the lateral
      venous sinus. Two female patients took oral contraceptives, 1 of whom also had a
      heterozygous factor V Leiden mutation. CONCLUSIONS: Cerebral sinus venous
      thrombosis may present with unspecific symptoms such as acute unilateral hearing
      loss. If in conjunction with headache or risk factors for venous thrombosis, the
      suspicion of ipsilateral lateral CSVT should prompt rapid imaging including
      venography.

PMID- 22869231
TI  - [Steatohepatitis--a challenge?].
AB  - CLINICAL/METHODICAL ISSUE: With the increasing use of cross-sectional imaging
      techniques both diffuse and focal fat accumulations in the liver are frequent
      incidental findings. Focal fatty changes in particular, such as localized
      distribution disorders in steatohepatitis or focal fat deposition of the liver,
      can lead to difficulties in the correct diagnosis of patients with a history of
      malignant disease. STANDARD RADIOLOGICAL METHODS: Ultrasound is used as the first
      imaging modality in most cases but has a relatively low sensitivity and
      specificity. In most cases a further diagnosis of diffuse fatty liver
      accumulations is possible with non-contrast computed tomography (CT) scanning and
      chemical shift imaging in magnetic resonance imaging (MRI) enabling an even
      further differential diagnostic distinction of fatty disorders of the liver.
      PERFORMANCE: For the detection of generalized fatty liver disease ultrasound has
      a sensitivity and specificity of 60-100% and 77-95%, respectively. Non-contrast
      CT of the liver attains a sensitivity of between 43% and 95% with a specificity
      of 90%. Sensitivity and specificity for chemical shift imaging of MRI are 81% and
      100%, respectively. PRACTICAL RECOMMENDATIONS: For advanced differential
      diagnostic distinction of the different forms of fatty liver disorders and for
      the correct diagnosis of benign and malignant liver lesions the leading imaging
      modality is chemical shift imaging of MRI (in-phase and opposed-phase).

PMID- 22869232
TI  - LASIK for presbyopia correction in emmetropic patients using aspheric ablation
      profiles and a micro-monovision protocol with the Carl Zeiss Meditec MEL 80 and
      VisuMax.
AB  - PURPOSE: To evaluate the monocular and binocular visual outcomes of LASIK with an
      aspheric micro-mono-vision protocol in emmetropic patients with presbyopia.
      METHODS: A retrospective, noncomparative case series included 296 eyes from 148
      consecutive emmetropic patients with presbyopia who were treated with LASIK
      induced micro-monovision. The CRS-Master software was used to generate ablation
      profiles for the MEL 80 excimer laser (Carl Zeiss Meditec) and flaps were created
      using the VisuMax femtosecond laser (Carl Zeiss Meditec). The target refraction
      was plano for distance eyes (dominant eye) and between -1.00 and -1.88 diopters
      (D) for near eyes. Patients were followed for 1 year. Emmetropia was defined for
      inclusion as spherical equivalent refraction ?- 0.88 D, sphere ?+1.00 D, and
      cylinder ?1.25 D. Median patient age was 55 years (range: 44 to 65 years). Median
      follow-up was 12.9 months. RESULTS: Mean deviation from intended correction was
      +0.02+/-0.35 D, with 91% within +/-0.50 D and 100% within +/-1.00 D. Of distance
      eyes, 95% achieved uncorrected distance visual acuity (UDVA) of 20/20 or better
      and 100% achieved 20/32 or better. Binocularly, 98% of patients achieved UDVA of
      20/20 or better and 100% achieved 20/32 or better; 96% achieved uncorrected near
      visual acuity of J2 and 99% could read J3 or better. No eyes lost 2 or more lines
      of corrected distance visual acuity. An average increase of 0.05 logMAR was noted
      in distance-corrected near visual acuity. A small increase occurred in mesopic
      contrast sensitivity (CSV-1000, VectorVision Inc) at 3 cycles per degree (cpd)
      (P=.016) and no change at 6, 12, or 18 cpd. CONCLUSIONS: This aspheric micro
      monovision protocol was a well-tolerated and effective procedure for treating
      emmetropic patients with presbyopia.

PMID- 22869233
TI  - Effect of Nd:YAG laser capsulotomy on refraction in multifocal apodized
      diffractive pseudophakia.
AB  - PURPOSE: To evaluate the effect on refraction of neodymium:YAG (Nd:YAG) laser
      posterior capsulotomy for posterior capsule opacification (PCO), and to evaluate
      the correlation between automated and subjective refraction in multifocal
      apodized diffractive pseudophakia. METHODS: A retrospective study of 75
      pseudophakic eyes (50 patients) with multifocal apodized diffractive
      pseudophakia, treated for PCO with Nd:YAG laser posterior capsulotomy, was
      performed. Pre- and postintervention values of refractive and visual parameters
      were compared. The outcomes of autorefraction and subjective refraction were also
      compared. RESULTS: Uncorrected and corrected distance visual acuity improved
      significantly after Nd:YAG capsulotomy (P<.001). No significant changes were
      noted in defocus equivalent, astigmatic power vectors J(0) and J(45), and overall
      blurring strength in subjective refraction and autorefraction. Spherical
      equivalent changed significantly in autorefraction (P=.008), but not in
      subjective refraction. Autorefraction and subjective refraction were highly
      correlated in spherical equivalent, defocus equivalent, and blurring strength
      (r(2)>0.59). In approximately 7% of eyes, a change of more than 0.50 diopters in
      spherical equivalent in subjective refraction occurred. CONCLUSIONS: In most
      cases, Nd:YAG laser capsulotomy in patients with multifocal pseudophakia did not
      result in a change in refraction. However, 7% of eyes experienced a significant
      change in subjective refraction. Autorefraction correlated well with subjective
      refraction in apodized diffractive multifocal IOLs.

PMID- 22869234
TI  - Comparison of keratometric data obtained by automated keratometer, Dicon CT 200,
      Allegro Topolyzer, and Pentacam.
AB  - PURPOSE: To compare the keratometric values measured by the automated
      keratometer, two Placido-based computerized topography systems (Dicon CT 200
      [Vismed Inc] and Allegro Topolyzer [WaveLight Inc]), and Scheimpflug analysis
      (Pentacam [Oculus Optikgerate GmbH]). METHODS: The keratometric data of 200 eyes
      from 200 patients evaluated for refractive surgery were reviewed retrospectively.
      Mean simulated keratometry (Sim K) and mean corneal astigmatism measured by the
      four devices were compared using repeated measures analysis of variance with
      Bonferroni correction. The analysis of agreement between two measurements was
      assessed using the method of Bland and Altman. RESULTS: Mean Sim K as measured by
      the automated keratometer, Dicon CT 200, Allegro Topolyzer, and Pentacam was
      43.39+/-1.50 diopters (D), 43.55+/-1.50 D, 43.45+/-1.50 D, and 43.43+/-1.45 D,
      respectively. The Dicon CT 200 measured the mean Sim K to be steeper and the
      automated keratometer measured the mean Sim K to be flatter than the other
      devices. Significant differences in corneal astigmatism were noted among the four
      devices except Dicon CT 200 versus Allegro Topolyzer and Allegro Topolyzer versus
      Pentacam comparisons (P<.013). For mean Sim K, the 95% limits of agreement
      between the Pentacam and other three devices were significantly wider than the
      other comparisons. In Bland-Altman plots comparing the Pentacam to the other
      devices, extreme outliers were present in 11 (5.5%) eyes. CONCLUSIONS: Because of
      the wide distribution range and presence of extreme outliers, Pentacam data
      should be used cautiously in IOL power calculation and astigmatic keratotomy
      procedures.

PMID- 22869236
TI  - Hypopyon uveitis following LASIK in a patient with ulcerative colitis.
AB  - PURPOSE: To present a case of unilateral hypopyon uveitis that began 15 days
      after uneventful bilateral LASIK in a 24-year-old man with an undisclosed history
      of ulcerative colitis. METHODS: Case report. RESULTS: The hypopyon uveitis
      completely resolved after treatment with aggressive topical and oral steroid
      agents in combination with topical antibiotic coverage. CONCLUSIONS: Although
      rare, visually significant hypopyon uveitis may arise after LASIK in the setting
      of ulcerative colitis and positive human leukocyte antigen (HLA) B27. Early
      recognition and treatment can result in an excellent outcome. The exact
      relationship between hypopyon uveitis and LASIK is impossible to ascertain.

PMID- 22869235
TI  - LASIK interface complications: etiology, management, and outcomes.
AB  - PURPOSE: To describe the etiology, diagnosis, clinical course, and management of
      LASIK interface complications. METHODS: Literature review. RESULTS: Primary
      interface complications include infectious keratitis, diffuse lamellar keratitis,
      central toxic keratopathy, pressure-induced stromal keratopathy (PISK), and
      epithelial ingrowth. Infectious keratitis is most commonly caused by Methicillin
      resistant Staphylococcus aureus (early onset) or atypical Mycobacterium (late
      onset) postoperatively, and immediate treatment includes flap lift and
      irrigation, cultures, and initiation of broad-spectrum topical antibiotics, with
      possible flap amputation for recalcitrant cases. Diffuse lamellar keratitis is a
      white blood cell infiltrate that appears within the first 5 days postoperatively
      and is acutely responsive to aggressive topical and oral steroid use in the early
      stages, but may require flap lift and irrigation to prevent flap necrosis if
      inflammation worsens. In contrast, PISK is caused by acute steroid response and
      resolves only with cessation of steroid use and intraocular pressure lowering.
      Without appropriate therapy PISK can result in severe optic nerve damage. Central
      toxic keratopathy mimics stage 4 diffuse lamellar keratitis, but occurs early in
      the postoperative period and is noninflammatory. Observation is the only
      effective treatment, and flap lift is usually not warranted. Epithelial ingrowth
      is easily distinguishable from other interface complications and may be self
      limited or require flap lift to treat irregular astigmatism and prevent flap
      melt. CONCLUSIONS: Differentiating between interface entities is critical to
      rapid appropriate diagnosis, treatment, and ultimate visual outcome. Although
      initial presentations may overlap significantly, the conditions can be readily
      distinguished with close follow-up, and most complications can resolve without
      significant visual sequelae when treated appropriately.

PMID- 22869237
TI  - Animal models of depression vulnerability.
AB  - The rapid increase in the number of proposed animal models of depression reflects
      the dissatisfaction with our current state of knowledge on neurobiology of
      depression and unsuccessful drug development. Results obtained with even the best
      validated models can be difficult to compare. Because evidence from
      epidemiological studies suggests that depression occurs in biologically
      predisposed subjects under the impact of adverse life events, increasing attempts
      have been made to use the diathesis-stress concept in animal models. In this way,
      factors underpinning vulnerability to depression have been identified by
      measuring behavioural traits analogous to facets of human personality, or created
      by inducing neurochemical lesions. Stressful interventions administered
      prenatally, in early life or in adulthood have been combined with other
      vulnerability factors including genetic changes. As a result, several putative
      animal models of endophenotypes of depression or depression vulnerability have
      been proposed. Diathesis-stress models may aid in separating adaptive and
      maladaptive strategies in coping with stress, and understanding the relevant
      neurobiology. Studies comparing effects of stress on males and females should
      reveal to which extent the pathogenetic processes leading to depression can be
      specific to sex/gender.

PMID- 22869238
TI  - Missed opportunities for treatment of uncontrolled hypertension at physician
      office visits in the United States, 2005 through 2009.

PMID- 22869239
TI  - Clinicopathologic characteristics and outcomes of surgery of middle-third gastric
      cancer.
AB  - Many issues of middle-third gastric cancer need to be address for obtaining
      preferably clinical treatment. The objective of this retrospective study was to
      analyze clinicopathologic characteristics and results of surgery for 113 middle
      third gastric cancer patients admitted to our hospital. Retrospective cohort
      analyses of clinicopathologic data and postoperative prognosis of 113 middle
      third gastric cancer patients who underwent curative resection between January
      1997 and December 2003 were reviewed. Compared with lower-third gastric cancer
      patients, middle-third gastric cancer patients had significantly lower 5-year
      survival rate (P < 0.001) and higher recurrence rate (P < 0.001). With the Cox
      proportional hazards model analysis, the types of gastrectomy (hazard ratio (HR)
      = 0.495, P = 0.012) and ratio between metastatic and dissected lymph nodes (RML)
      (HR = 1.681, P < 0.001) were identified as the independent predictors of overall
      survival (OS) of middle-third gastric cancer patients. Besides, only RML (HR =
      3.026, P < 0.001) was an independent predictor of recurrence for middle-third
      gastric cancer patients after surgery identified using the logistic regression
      analysis. The prognosis of middle-third gastric cancer was significantly worse
      than lower-third gastric cancer. RML was a key indicator for OS and recurrence of
      middle-third gastric cancer.

PMID- 22869240
TI  - Candida sanyaensis sp. nov., an ascomycetous yeast species isolated from soil.
AB  - Strains representing a novel ascomycetous yeast species, Candida sanyaensis, were
      isolated from soil samples collected on Hainan Island and Taiwan Island in China.
      Analysis of the D1/D2 domains of the large subunit (LUS) rRNA gene and internal
      transcribed spacer (ITS) regions of these strains showed that this species was
      related to Candida tropicalis and Candida sojae, their closest relatives. C.
      sanyaensis differed by three substitutions and one gap from C. tropicalis, and by
      four substitutions and one gap from C. sojae, in the D1/D2 domain sequences.
      However, the ITS sequences of C. sanyaensis were quite divergent from the latter
      two species, showing that it is a genetically separate species. The novel strains
      were also found to have very similar PCR-fingerprinting profiles which were quite
      distinct from those of C. tropicalis and C. sojae strains. The type strain of C.
      sanyaensis is HN-26(T) (= CICC 1979(T) = CBS 12637(T)).

PMID- 22869242
TI  - Educating for health equity: walking the walk.
AB  - "Transforming education to strengthen health systems in an interdependent world"
      is the subtitle to a report by a global commission on health professional
      education, Health Professionals for a New Century (HPNC). The report aspires to
      do for health professional education in this century what Flexner did for medical
      education in the last-spark a revolution.[1] And indeed a necessary one if we are
      to see global health equity in practice, not simply in print.

PMID- 22869241
TI  - Effect of n-3 fatty acids and alpha-tocopherol on post-thaw parameters and fatty
      acid composition of bovine sperm.
AB  - PURPOSE: This study was designed to determine the combined effects of adding
      source of n-3 fatty acids (FA) and alpha-tocopherol (vitamin E, VE) to semen
      extender on freezability and FA composition of Brown Swiss bull sperm. METHODS:
      Semen samples were collected from 6 Brown Swiss bulls and pooled. In the first
      trial, semen was divided into 12 groups including 4 levels of n-3 FA (0, 1, 10,
      100 ng ml(-1)) and 3 levels of VE (0. 0.2, 0.4 mM). Motility, viability and fatty
      acid composition of sperm were measured. RESULTS: The treatment of 10 ng ml(-1) n
      3 FA and 0.4 mM VE had the best post-thaw sperm characteristics (P < 0.01). In
      the second trial, sperm lipid composition of this treatment and control (without
      FA and VE) was determined. Supplementing n-3 fatty acids during cryopreservation
      increased docosahexaenoic acid (DHA) and the ratio of n-3 to n-6 FA in sperm
      before freezing and after thawing. CONCLUSIONS: The results suggest that
      combining the optimal level of n-3 FA (10 ng ml(-1)) with the highest level of VE
      tested (0.4 mM) in a semen extender changed the membrane lipid composition and
      improved freezablity of Brown Swiss bull sperm.

PMID- 22869243
TI  - Cuba's Latin American Medical School: can socially-accountable medical education
      make a difference?
AB  - After graduating more than 12,000 doctors since its founding in 1999, Cuba's
      Latin American Medical School (ELAM, the Spanish acronym) is tackling one of its
      greatest challenges to date: how to track graduates from over 65 countries and
      measure their impact on health outcomes and policy in their local contexts?

PMID- 22869244
TI  - Developing nursing capacity for health systems and services research in Cuba,
      2008-2011.
AB  - INTRODUCTION: Health systems and services research by nursing personnel could
      inform decision-making and nursing care, providing evidence concerning quality of
      and patient satisfaction. Such studies are rather uncommon in Cuban research
      institutes, where clinical research predominates. OBJECTIVE: Assess the results
      of a strategy implemented between 2008 and 2011 to develop nursing capacity for
      health systems and services research in 14 national research institutes based in
      Havana. METHODS: The study comprised four stages: description of approaches to
      health systems and services research by nurses worldwide and in Cuba; analysis of
      current capacities for such research in Cuba; intervention design and
      implementation; and evaluation. Various techniques were used including:
      literature review, bibliometric analysis, questionnaire survey, consultation with
      experts, focus groups, and workshops for participant orientation and design and
      followup of research projects. Qualitative information reduction and quantitative
      information summary methods were used. Initially, 32 nursing managers
      participated; a further 105 nurses from the institutes were involved in research
      teams formed during intervention implementation. RESULTS: Of all published
      nursing research articles retrieved, 8.9% (185 of 2081) concerned health systems
      and services research, of which 26.5% (49 of 185) dealt with quality assessment.
      At baseline, 75% of Cuban nurses surveyed had poor knowledge of health systems
      and services research. Orientation, design and followup workshops for all
      institute teams developed individual and institutional capacity for health
      systems and services research. Post-intervention, 84.7% (27) of nurses reached
      good knowledge and 14.3% (5) fair; institutional research teams were formed and
      maintained in 9 institutes, and 13 projects designed and implemented (11
      institutional, 2 addressing ministerial-level priorities) to research nursing
      issues at selected centers. CONCLUSIONS: A systematic strategy to build nursing
      capacity for health systems and services research can be effective in involving
      nurses in such research and in developing institutional support for it, fostering
      compliance with Cuban and international professional development priorities for
      nursing, as well as contributing to quality of patient services.

PMID- 22869245
TI  - Assessment of a complementary curricular strategy for training South African
      physicians in a Cuban medical university.
AB  - INTRODUCTION: One reason given by the South African government for establishing a
      physician training agreement with Cuba is that the ethical, humanistic and
      solidarity principles promoted in Cuban medical education are difficult to
      acquire in other settings. However, Cuba's general medical training program does
      not provide all skills needed by a general practitioner in South Africa: other
      competencies are required, such as management of general and gynecological or
      obstetrical surgical emergencies, administration of anesthesia and nursing
      procedures. As long as the desired humanistic values were assured, South African
      authorities have preferred to complement these competencies. Thus, since 2003,
      the Medical University of Villa Clara has applied a curricular strategy of 12
      complementary courses to develop the requested additional skills, but results
      have not met expectations. OBJECTIVE: Determine why the complementary curricular
      strategy has not been entirely successful and identify possible courses of action
      for improvement. METHODS: A document review was conducted of the curricular
      strategy applied and of minutes of meetings between Cuban and South African
      counterparts to identify correspondence between requested professional skills and
      actions to develop them. In addition, South African students were surveyed and
      Cuban professors were interviewed in depth. Senior university administrators and
      key informants were also interviewed. Variables assessed were course quality and
      satisfaction of students and professors. RESULTS: Some actions originally
      included in the curricular strategy were not implemented and there were
      structural weaknesses in complementary courses, primarily in objectives, teaching
      strategy and evaluation. Students reported insufficient practical activities and
      lack of relationship between content and the health situation in South Africa.
      Professors were dissatisfied with student levels of motivation and ability to
      manage their own learning. Other influencing factors were insufficient academic
      management and professors' lack of knowledge about the context where these future
      professionals would eventually practice. CONCLUSIONS: Curricular strategy
      deficiencies detected are primarily in academic management; overcoming them could
      facilitate action in specific directions identified to improve the requested
      skill levels.

PMID- 22869246
TI  - Continuous venovenous hemodiafiltration in patients with multiple organ
      dysfunction syndrome in an intensive care unit.
AB  - INTRODUCTION: Continuous venovenous hemodiafiltration, generally used in patients
      with acute renal failure, enables elimination of humoral mediators of systemic
      inflammatory response and sepsis from blood. This effect should improve treatment
      results in patients with multiple organ dysfunction, but evidence of improved
      survival is insufficient. OBJECTIVES: Describe the effect of continuous
      venovenous hemodiaflitration on patients with multiple organ dysfunction syndrome
      in terms of systemic and brain hemodynamics, oxygenation, metabolism and status
      on ICU separation. METHODS: An observational case series was done of 18 patients
      (11 men and 7 women) aged 24-78 years with multiple organ dysfunction syndrome
      treated with continuous venovenous hemodiafiltration in the Medical-Surgical
      Research Center's ICU in Havana. General, systemic and brain hemodynamic,
      oxygenation and metabolic variables were assessed immediately before and 12 hours
      after starting the procedure; vital status on separation from intensive care was
      recorded. For analysis, patients were grouped by whether cause of multiple organ
      dysfunction syndrome was septic or nonseptic. Variable means before and after
      treatment were compared using the Wilcoxon matched pairs test. Standardized
      mortality ratios were calculated for both groups, with survival efficacy defined
      by a ratio of <0.9. RESULTS: After 12 hours continuous venovenous
      hemodiafitration, the septic group showed clinical improvement, with
      statistically significant improvement in all variables except mean arterial
      pressure and brain hemodynamics. Survival to discharge from ICU was 64%, with a
      standardized mortality ratio of 0.66. In the nonseptic group, survival was 0% and
      ratio was 2.13; temperature was the only variable found to improve significantly.
      CONCLUSIONS: Continuous venovenous hemodiafltration improved clinical parameters
      and survival in patients with multiple organ dysfunction of septic origin.
      Further studies are needed with larger numbers of patients to corroborate these
      results.

PMID- 22869247
TI  - Possible predictors of poor angiogenesis after hematopoietic stem cell autograft
      for lower limb ischemia.
AB  - INTRODUCTION: The therapeutic potential of adult stem cells in coronary and
      peripheral arterial diseases has been proposed in recent years. However, factors
      possibly predictive of unfavorable angiogenic results have not been clearly
      identified as yet. OBJECTIVES: Identify candidate predictors of poor
      angiogenesis, as indicated by need for amputation, after autologous hematopoietic
      stem cell transplantation for chronic lower limb ischemia. METHODS: A
      retrospective analytical case-series study was carried out to detect factors
      possibly associated with hematopoietic stem cell autograft failure due to low
      angiogenic potential. The study universe was composed of 47 patients (19 women,
      28 men) with critical lower limb ischemia in Fontaine stages IIb, III and IV, who
      received autologous stem cell transplantation at the Dr Gustavo Aldereguia Lima
      University General Hospital in Cienfuegos, Cuba, from January 2007 through
      December 2010. Variables studied were sex, age, medical history (high blood
      pressure, ischemic cardiomyopathy, diabetes mellitus and chronic renal
      insufficiency), Fontaine ischemia stage, intermittent claudication, pain score on
      a 1-10 scale, ankle-brachial pressure index in the affected extremity, presence
      of ulcers, and smoking. Laboratory variables included: blood concentrations of
      hemoglobin, glucose, creatinine, liver enzymes, cholesterol, triglycerides and
      LDH; as well as leukocyte and platelet counts, stem cell viability, prothrombin
      time and erythrocyte sedimentation rate. The main response variable was
      amputation, an indicator of poor angiogenesis. Using logistic regression, a
      prognostic score of 1 to 4 was developed for each risk factor and scores added to
      create a risk prediction scale. Predicted risk for amputation and observed
      amputation rates were compared for patients in three risk groups: low, 0-4;
      medium, 5-8; and high, 9-12. RESULTS: Factors identified as possibly predictive
      of poor angiogenesis were: final leukocyte count <20 x 109/L after mobilization
      with granulocyte colony stimulating factor; age >=60 years; pain scale score of
      10; glycemia of >6 mmol/L; and triglycerides of >1.8 mmol/L. Patients who scored
      low on predicted amputation risk scale were spared amputation in 90.9% (10/11) of
      cases, versus 16.7% (2/12) in patients scoring high. CONCLUSIONS: Five possible
      prognostic factors for low angiogenic potential in stem cell autotransplantation
      were identified and a preliminary scale established to predict in which patients
      autotransplantation would be more likely to be successful.

PMID- 22869248
TI  - Cataract and pterygium surgery results in Venezuelan patients treated in the
      Mision Milagro program.
AB  - An intervention to address vision loss was carried out in 2008 in Tachira,
      Venezuela, by health teams of the joint Cuban-Venezuelan initiative known as
      Mision Milagro. It included active case identification of patients with
      ophthalmologic conditions and, where warranted, surgery, followup, rehabilitation
      and medical discharge. From a universe of 345 patients aged >=18 years with
      ophthalmologic conditions found, 210 were selected for cataract or pterygium
      surgery. Of cataract patients, 55.2% recovered optimal vision within three months
      after surgery, as did 90.9% of those with pterygium; frequency of complications
      was 15.4% in cataract patients and 41.7% in pterygium patients. The intervention
      was considered successful, although many patients' low-income status required
      premature postoperative return to their jobs and other labors, a factor
      considered detrimental to optimal recovery.

PMID- 22869249
TI  - Changes needed in basic biomedical sciences teaching in Cuban medical schools.
AB  - In the 20th century, the basic biomedical sciences (particularly anatomy,
      histology, embryology, physiology and biochemistry) were taught predominantly in
      the first semesters of Cuban medical education, with differing curricular
      connections between these and the clinical sciences. Establishment of the
      University Polyclinic Program in 2004 laid the foundation for integration of
      basic biomedical sciences into a transdisciplinary unit designated
      morphophysiology. This paper argues for improvements in this curricular unit and
      in its coordination with family medicine in the first semesters of medical
      training, complemented by integration of basic biomedical sciences into family
      medicine clinical courses throughout the remainder of the six-year curriculum.
      KEYWORDS Medical laboratory science, medical clinical science, medical education,
      curriculum, biological science disciplines, interdisciplinary communication,
      transfer of learning, Cuba.

PMID- 22869250
TI  - Contributions of bioethics to health sector leadership.
AB  - Leadership is the perception or acceptance by members of a group of their
      superior's ability to inspire, influence and motivate them to meet their goals
      and contribute to the achievement of shared objectives. This article analyzes the
      characteristics of bioethics and the profile of the bioethicist in relation to
      the comprehensive development required of health leaders. We address this
      relationship in the areas of research and clinical practice; intersectoral
      activity; health sciences education; bioethicist's profile; and influence on
      organizational structures, functioning and decisionmaking, with particular
      reference to development and current situation of these aspects in Cuba. KEYWORDS
      Bioethics, leadership, medical education, health professional education, health,
      values, workplace stress, Cuba.

PMID- 22869251
TI  - The vocation to serve: cornerstone of health care.
AB  - Twenty-five hundred years ago, Hippocrates bequeathed a set of ethical precepts
      that emphasized the social transcendence of the practice of medicine and the
      profound commitment of physicians to serve patients and their families selflessly
      and with a pure heart.[1] Traditionally, small-town medical practice facilitated
      spontaneous interpersonal relationships between family doctors and nurses and
      their patients. Later, however, centralization of health services in large
      medical complexes, an explosion of technology not always wisely deployed,
      litigiousness, tabloid journalism and commercialism in health service provision
      have created conditions that are, to say the least, less than propitious for
      optimal satisfaction on the part of patients and families. In my view, this has
      been accompanied by a dangerous devaluation of clinical skills, of medicine as a
      vocation, and by deterioration in the relationship of physicians and other health
      professionals with patients and their families.

PMID- 22869252
TI  - Post-sternotomy chronic osteomyelitis: is sternal resection always necessary?
AB  - OBJECTIVES: The goal of this study was to investigate alternative strategies to
      the sternal resection in the treatment of post-sternotomy osteomyelitis. We
      report our experience in the treatment of chronic infection of median sternotomy
      following open heart surgery without sternal resection. METHODS: A 4-year
      retrospective study was performed, consisting of 70 patients affected by post
      sternotomy sternocutaneous fistulas due to chronic osteomyelitis: 45 patients
      underwent only medical treatment and 25 underwent steel wire removal and surgical
      debridement (conservative surgery). Of the 25, 7 patients underwent an additional
      vacuum assisted closure (VAC) therapy due to widespread infected subcutaneous
      tissue. The diagnosis of osteomyelitis was supported via 3D CT scan images.
      RESULTS: Complete wound healing was achieved in 67 patients including a patient
      who achieved healing after being affected by a fistula for over 24 years before
      coming under our observation, another, affected by mycobacteria other than
      tuberculosis osteomyelitis, who needed antimicrobial treatment for a period of 30
      months and 2 who were affected by Aspergillus infection and needed radical
      cartilage removal. Fistula relapses were observed in 6 patients of the total 70,
      possibly due to the too short-term antibiotic therapy used in the presence of
      coagulase-negative Staphylococcus (CoNS) with multiple resistances and in the
      presence of Corynebacterium species. CONCLUSIONS: Post-sternotomy chronic
      osteomyelitis can be successfully treated mainly by systemic antimicrobial
      therapy alone, without mandatory surgical treatments, provided that accurate
      microbiological and radiological studies are performed. The presence of CoNS and
      Corynebacterium species seemed to be associated with a need for a prolonged
      combined antimicrobial therapy with a minimum of 6 months up to a maximum of 18
      months. The CT scan and the 3D reconstruction of the sternum proved to be a good
      method to evaluate the status of the sternum and support the treatments. The VAC
      therapy was not useful in treating osteomyelitis, although, if used appropriately
      in the postoperative deep sternal wound infection with the sponge fitted between
      the sternal edges, it seems to be an effective method to eradicate the infection
      in the sternum and to prevent chronic osteomyelitis.

PMID- 22869253
TI  - Actual situation in Eurotransplant regarding high urgent heart transplantation.

PMID- 22869254
TI  - Removing the cells from adult bone marrow derived stem cell therapy does not
      eliminate cardioprotection.
AB  - OBJECTIVES: The debate as to whether adult stem cell therapy is regenerative or
      not continues. The non-regenerative benefits of adult bone marrow-derived stem
      cell therapy were investigated by testing whether the supernatant derived from
      unfractionated bone marrow mononuclear cells might be cardioprotective in an
      animal model of myocardial ischaemia-reperfusion injury. METHODS: Regional
      myocardial reperfusion injury was acquired by 25 min reversible left anterior
      descending coronary artery (LAD) occlusion followed by 2 h reperfusion, in
      anaesthetized Wistar male rats. Unfractionated bone marrow mononuclear cells
      (BMMNC) isolated from sibling Wistar male rat whole bone marrow were phenotyped
      by fluorescence activated cell sorting flowcytometry for the haematopoietic stem
      cell surface markers c-kit, CD34, CD45 and CD133. Animals subjected to regional
      myocardial reperfusion injury received either 10 million BMMNC or BMMNC
      supernatant (BMS); both were collected in 0.5 ml phosphate-buffered saline and
      delivered by intravenous bolus at the onset of reperfusion. The left ventricular
      region distal to the LAD occlusion point was excised for measurement of
      myocardial infarct size and proteomic analysis, which was used to identify
      whether there were any differences in myocardial proteins associated with
      intravenous injection of either BMMNC or BMS. RESULTS: BMMNC were phenotyped to
      be c-kit(+) (7 +/- 1%), CD34(+) (7 +/- 1%), CD45(+) (54 +/- 6%), CD133(+) (15 +/-
      1%). The supernatant reduced myocardial infarct size (BMS 34 +/- 2%, n = 15 vs
      control 57 +/- 2%, n = 7, P < 0.0001), which was comparable to the reduction in
      infarct size afforded by the injection of cells (BMMNC 33 +/- 3% vs control 57 +/
      2%, n = 10, P < 0.0001). Proteomics of hearts treated with either BMS or BMMNC
      demonstrated higher expression of (i) anti-apoptotic signal transduction protein:
      14-3-3-epsilon (1.5-fold); (ii) anti-oxidants: peroxiredoxin-6 (2.1-fold); (iii)
      heat shock proteins: alpha B-crystallin (1.7-fold), heat shock protein 72 (2.8
      fold), tumour necrosis factor receptor-1 associated protein (2.3-fold), ischaemia
      responsive protein-94 (1.6-fold); (iv) glycolytic protein: glyceraldehyde-3
      phosphate dehydrogenase (2.3-fold); (v) mitochondrial respiratory proteins:
      mitochondrial aconitase (4.7-fold), voltage-dependent anion-selective channel
      protein-1 (VDAC-1) (2.7-fold). CONCLUSIONS: Regional myocardial reperfusion
      injury can be attenuated by intravenous administration of either BMMNC or BMS at
      the onset of reperfusion, which suggests adult stem cells mediate non
      regenerative cardioprotection.

PMID- 22869255
TI  - Pathologic and clinical features of pituitary adenomas showing TSH
      immunoreactivity.
AB  - Patients with thyrotropin-secreting pituitary adenomas may present with mass
      effect, hypopituitarism, and/or hyperthyroidism. The spectrum of pathologic and
      clinical features of patients whose tumors demonstrate beta-thyrotropin
      immunoreactivity (beta-TSH IR) has not been characterized. To characterize the
      phenotype of patients with pituitary adenomas with positive beta-TSH IR, we
      conducted a retrospective analysis of patient records of all adult patients (n =
      1,223) undergoing pituitary surgery in our institution over one decade (1999
      2009). The search identified 166 adults with tumors which had beta-TSH IR. These
      patients were individually matched to 166 patients whose tumors revealed no beta
      TSH IR. Clinical, pathological, imaging and biochemical data were extracted. 332
      patients, aged 51.4 +/- 15.1 years [150 women (45 %) and 182 men (55 %)], with
      pituitary adenomas (mean tumor diameter +/- SD: 22.7 +/- 9.0 mm) were studied.
      The degree of beta-TSH IR was associated with the presence of central
      hyperthyroidism (p < 0.0001) or goiter (p = 0.0217). Patients whose tumors
      expressed more extensive beta-TSH IR were less likely to develop pituitary
      apoplexy than those without beta-TSH IR (p = 0.0428). In addition, the degree of
      beta-TSH IR correlated with the presence of immunoreactivity for beta-FSH (p <
      0.0001), beta-LH (p < 0.0001), alpha subunit (p < 0.0001), and GH (p = 0.0036).
      CONCLUSIONS: Pituitary adenomas expressing beta-TSH IR were more likely to
      demonstrate immunoreactivity for beta-FSH, beta-LH, GH or alpha subunit. Patients
      with such tumors were more likely to exhibit hyperthyroidism and goiter, but less
      likely to develop pituitary apoplexy than patients without beta-TSH IR. These
      findings suggest that beta-TSH IR is associated with specific phenotypic features
      in patients with pituitary adenomas.

PMID- 22869256
TI  - Chronic subdural haematomas: a comparative study of an enlarged single burr hole
      versus double burr hole drainage.
AB  - Various surgical treatments have been proposed for the treatment of chronic
      subdural haematoma (CSDH). Herewith, we set out to compare the efficacy of an
      enlarged single burr hole versus double burr hole drainage for the treatment of
      CSDH. We studied patients with symptomatic CSDH proven by CT scan that were
      treated in our institute between January 2002 and January 2009. All patients were
      treated by an enlarged single or double burr hole drainage. A subdural drain was
      placed in all cases. A total of 245 patients were included in the study. Double
      hole drainage was performed in 156 (63.7%) patients (group A) and an enlarged
      single burr hole drainage in 89 (36.3%) patients (group B). There were nine
      recurrences in group A and five in group B; however, the difference was not
      statistically significant. There was no significant relationship between
      recurrence rate and age, gender, bilateral haematoma and antiplatelet or
      anticoagulant therapy. There was a trend towards higher risk of recurrence for
      patients with residual clots on postoperative CT scan. The mean hospitalization
      time was 6.2 days, and there was no significant difference between the two
      groups. No significant difference was found between patients' outcome, as
      assessed by Glasgow outcome scale score, and treatment method. Enlarged single
      burr hole and double burr hole drainage had the same efficacy in the treatment of
      CSDH.

PMID- 22869257
TI  - Arginine residues in the C-terminal and their relationship with the analgesic
      activity of the toxin from the Chinese scorpion Buthus martensii Karsch (BmK AGP
      SYPU1).
AB  - In this study, we investigated the functional role of arginines in the C-terminal
      (65-67) of BmK AGP-SYPU1, an analgesic peptide from the Chinese scorpion Buthus
      martensii Karsch. Using site-directed mutagenesis, arginines at the C-terminal
      (65-66) were deleted or added to the C-terminal (67). The genes for three mutants
      of BmK AGP-SYPU1 were obtained by PCR. An analgesic activity assay was used to
      evaluate the role of arginine residues in the analgesic activity. The three
      dimensional structure of BmK AGP-SYPU1 was established by homology modeling. As a
      result, we showed that the arginines in the C-terminal are crucial for the
      analgesic activity and may be located at analgesic functional sites. Our work has
      implications for further modification of scorpion toxins to obtain new analgesic
      peptides with enhanced activity.

PMID- 22869258
TI  - Development of a modified surveillance definition of central line-associated
      bloodstream infections for patients with hematologic malignancies.
AB  - OBJECTIVE: To develop a modified surveillance definition of central line
      associated bloodstream infection (mCLABSI) specific for our population of
      patients with hematologic malignancies to better support ongoing improvement
      efforts at our hospital. DESIGN: Retrospective cohort study. PATIENTS:
      Hematologic malignancies population in a 1,200-bed tertiary care hospital on a 22
      bed bone marrow transplant (BMT) unit and a 22-bed leukemia unit. METHODS: An
      mCLABSI definition was developed, and pathogens and rates were compared against
      those determined using the National Healthcare Safety Network (NHSN) definition.
      RESULTS: By the NHSN definition the CLABSI rate on the BMT unit was 6.0 per 1,000
      central line-days, and by the mCLABSI definition the rate was 2.0 per 1,000 line
      days ([Formula: see text]). On the leukemia unit, the NHSN CLABSI rate was 14.4
      per 1,000 line-days, and the mCLABSI rate was 8.2 per 1,000 line-days ([Formula:
      see text]). The top 3 CLABSI pathogens by the NHSN definition were Enterococcus
      species, Klebsiella species, and Escherichia coli. The top 3 CLABSI pathogens by
      the mCLABSI definition were coagulase-negative Staphylococcus (CONS), Pseudomonas
      aeruginosa, and Staphylococcus aureus. The difference in the incidence of CONS as
      a cause of CLABSI under the 2 definitions was statistically significant
      ([Formula: see text]). CONCLUSIONS: A modified surveillance definition of CLABSI
      was associated with an increase in the identification of staphylococci as the
      cause of CLABSIs, as opposed to enteric pathogens, and a decrease in CLABSI
      rates.

PMID- 22869259
TI  - Central line-associated bloodstream infection surveillance outside the intensive
      care unit: a multicenter survey.
AB  - OBJECTIVE: The success of central line-associated bloodstream infection (CLABSI)
      prevention programs in intensive care units (ICUs) has led to the expansion of
      surveillance at many hospitals. We sought to compare non-ICU CLABSI (nCLABSI)
      rates with national reports and describe methods of surveillance at several
      participating US institutions. DESIGN AND SETTING: An electronic survey of
      several medical centers about infection surveillance practices and rate data for
      non-ICU patients. PARTICIPANTS: Ten tertiary care hospitals. METHODS: In March
      2011, a survey was sent to 10 medical centers. The survey consisted of 12
      questions regarding demographics and CLABSI surveillance methodology for non-ICU
      patients at each center. Participants were also asked to provide available rate
      and device utilization data. RESULTS: Hospitals ranged in size from 238 to 1,400
      total beds (median, 815). All hospitals reported using Centers for Disease
      Control and Prevention (CDC) definitions. Denominators were collected by
      different means: counting patients with central lines every day (5 hospitals),
      indirectly estimating on the basis of electronic orders ([Formula: see text]), or
      another automated method ([Formula: see text]). Rates of nCLABSI ranged from 0.2
      to 4.2 infections per 1,000 catheter-days (median, 2.5). The national rate
      reported by the CDC using 2009 data from the National Healthcare Surveillance
      Network was 1.14 infections per 1,000 catheter-days. CONCLUSIONS: Only 2
      hospitals were below the pooled CLABSI rate for inpatient wards; all others
      exceeded this rate. Possible explanations include differences in average central
      line utilization or hospital size in the impact of certain clinical risk factors
      notably absent from the definition and in interpretation and reporting practices.
      Further investigation is necessary to determine whether the national benchmarks
      are low or whether the hospitals surveyed here represent a selection of outliers.

PMID- 22869260
TI  - Diagnosing and reporting of central line-associated bloodstream infections.
AB  - BACKGROUND: The diagnosis of central line-associated bloodstream infections
      (CLABSIs) is often controversial, and existing guidelines differ in important
      ways. OBJECTIVE: To determine both the range of practices involved in obtaining
      blood culture samples and how central line-associated infections are diagnosed
      and to obtain members' opinions regarding the process of designating bloodstream
      infections as publicly reportable CLABSIs. DESIGN: Electronic and paper 11
      question survey of infectious-diseases physician members of the Infectious
      Diseases Society of America Emerging Infections Network (IDSA EIN). PARTICIPANTS:
      All 1,364 IDSA EIN members were invited to participate. RESULTS: 692 (51%)
      members responded; 52% of respondents with adult practices reported that more
      than half of the blood culture samples for intensive care unit (ICU) patients
      with central lines were drawn through existing lines. A sizable majority of
      respondents used time to positivity, differential time to positivity when paired
      blood cultures are used, and quantitative culture of catheter tips when
      diagnosing CLABSI or determining the source of that bacteremia. When determining
      whether a bacteremia met the reportable CLABSI definition, a majority used a
      decision method that involved clinical judgment. CONCLUSIONS: Our survey
      documents a strong preference for drawing 1 set of blood culture samples from a
      peripheral line and 1 from the central line when evaluating fever in an ICU
      patient, as recommended by IDSA guidelines and in contrast to current Centers for
      Disease Control and Prevention recommendations. Our data show substantial
      variability when infectious-diseases physicians were asked to determine whether
      bloodstream infections were primary bacteremias, and therefore subject to public
      reporting by National Healthcare Safety Network guidelines, or secondary
      bacteremias, which are not reportable.

PMID- 22869261
TI  - Assessing the burden of Acinetobacter baumannii in Maryland: a statewide cross
      sectional period prevalence survey.
AB  - OBJECTIVE: To determine the prevalence of Acinetobacter baumannii, an important
      healthcare-associated pathogen, among mechanically ventilated patients in
      Maryland. DESIGN: The Maryland MDRO Prevention Collaborative performed a
      statewide cross-sectional active surveillance survey of mechanically ventilated
      patients residing in acute care and long-term care (LTC) facilities. Surveillance
      cultures (sputum and perianal) were obtained from all mechanically ventilated
      inpatients at participating facilities during a 2-week period. SETTING: All
      healthcare facilities in Maryland that provide care for mechanically ventilated
      patients were invited to participate. PATIENTS: Mechanically ventilated patients,
      known to be at high risk for colonization and infection with A. baumannii, were
      included. RESULTS: Seventy percent (40/57) of all eligible healthcare facilities
      participated in the survey, representing both acute care ([Formula: see text])
      and LTC ([Formula: see text]) facilities in all geographic regions of Maryland.
      Surveillance cultures were obtained from 92% (358/390) of eligible patients. A.
      baumannii was identified in 34% of all mechanically ventilated patients in
      Maryland; multidrug-resistant A. baumannii was found in 27% of all patients. A.
      baumannii was detected in at least 1 patient in 49% of participating facilities;
      100% of LTC facilities had at least 1 patient with A. baumannii, compared with
      31% of acute care facilities. A. baumannii was identified from all facilities in
      which 10 or more patients were sampled. CONCLUSIONS: A. baumannii is common among
      mechanically ventilated patients in both acute care and LTC facilities throughout
      Maryland, with a high proportion of isolates demonstrating multidrug resistance.

PMID- 22869262
TI  - Relationship between chlorhexidine gluconate skin concentration and microbial
      density on the skin of critically ill patients bathed daily with chlorhexidine
      gluconate.
AB  - OBJECTIVE AND DESIGN: Previous work has shown that daily skin cleansing with
      chlorhexidine gluconate (CHG) is effective in preventing infection in the medical
      intensive care unit (MICU). A colorimetric, semiquantitative indicator was used
      to measure CHG concentration on skin (neck, antecubital fossae, and inguinal
      areas) of patients bathed daily with CHG during their MICU stay and after
      discharge from the MICU, when CHG bathing stopped. PATIENTS AND SETTING: MICU
      patients at Rush University Medical Center. METHODS: CHG concentration on skin
      was measured and skin sites were cultured quantitatively. The relationship
      between CHG concentration and microbial density on skin was explored in a mixed
      effects model using gram-positive colony-forming unit (CFU) counts. RESULTS: For
      20 MICU patients studied (240 measurements), the lowest CHG concentrations (0
      18.75 MUg/mL) and the highest gram-positive CFU counts were on the neck (median,
      1.07 log(10) CFUs; [Formula: see text]). CHG concentration increased postbath and
      decreased over 24 hours ([Formula: see text]). In parallel, median log(10) CFUs
      decreased pre- to postbath (0.78 to 0) and then increased over 24 hours to the
      baseline of 0.78 ([Formula: see text]). A CHG concentration above 18.75 MUg/mL
      was associated with decreased gram-positive CFUs ([Formula: see text]). In all
      but 2 instances, CHG was detected on patient skin during the entire interbath
      (approximately 24-hour) period (18 [90%] of 20 patients). In 11 patients studied
      after MICU discharge (80 measurements), CHG skin concentrations fell below
      effective levels after 1-3 days. CONCLUSION: In MICU patients bathed daily with
      CHG, CHG concentration was inversely associated with microbial density on skin;
      residual antimicrobial activity on skin persisted up to 24 hours. Determination
      of CHG concentration on the skin of patients may be useful in monitoring the
      adequacy of skin cleansing by healthcare workers.

PMID- 22869263
TI  - Decreasing operating room environmental pathogen contamination through improved
      cleaning practice.
AB  - OBJECTIVE: Potential transmission of organisms from the environment to patients
      is a concern, especially in enclosed settings, such as operating rooms, in which
      there are multiple and frequent contacts between patients, provider's hands, and
      environmental surfaces. Therefore, adequate disinfection of operating rooms is
      essential. We aimed to determine the change in both the thoroughness of
      environmental cleaning and the proportion of environmental surfaces within
      operating rooms from which pathogenic organisms were recovered. DESIGN:
      Prospective environmental study using feedback with UV markers and environmental
      cultures. SETTING: A 1,500-bed county teaching hospital. PARTICIPANTS:
      Environmental service personnel, hospital administration, and medical and nursing
      leadership. RESULTS: The proportion of UV markers removed (cleaned) increased
      from 0.47 (284 of 600 markers; 95% confidence interval [CI], 0.42-0.53) at
      baseline to 0.82 (634 of 777 markers; 95% CI, 0.77-0.85) during the last month of
      observations ([Formula: see text]). Nevertheless, the percentage of samples from
      which pathogenic organisms (gram-negative bacilli, Staphylococcus aureus, and
      Enterococcus species) were recovered did not change throughout our study.
      Pathogens were identified on 16.6% of surfaces at baseline and 12.5% of surfaces
      during the follow-up period ([Formula: see text]). However, the percentage of
      surfaces from which gram-negative bacilli were recovered decreased from 10.7% at
      baseline to 2.3% during the follow-up period ([Formula: see text]). CONCLUSIONS:
      Feedback using Gram staining of environmental cultures and UV markers was
      successful at improving the degree of cleaning in our operating rooms.

PMID- 22869264
TI  - Evaluation of potential environmental contamination sources for the presence of
      multidrug-resistant bacteria linked to wound infections in combat casualties.
AB  - OBJECTIVE: To determine whether multidrug-resistant (MDR) gram-negative organisms
      are present in Afghanistan or Iraq soil samples, contaminate standard deployed
      hospital or modular operating rooms (ORs), or aerosolize during surgical
      procedures. DESIGN: Active surveillance. SETTING: US military hospitals in the
      United States, Afghanistan, and Iraq. METHODS: Soil samples were collected from
      sites throughout Afghanistan and Iraq and analyzed for presence of MDR bacteria.
      Environmental sampling of selected newly established modular and deployed OR high
      touch surfaces and equipment was performed to determine the presence of bacterial
      contamination. Gram-negative bacteria aerosolization during OR surgical
      procedures was determined by microbiological analysis of settle plate growth.
      RESULTS: Subsurface soil sample isolates recovered in Afghanistan and Iraq
      included various pansusceptible members of Enterobacteriaceae, Vibrio species,
      Pseudomonas species, Acinetobacter lwoffii, and coagulase-negative Staphylococcus
      (CNS). OR contamination studies in Afghanistan revealed 1 surface with a
      Micrococcus luteus. Newly established US-based modular ORs and the colocated
      fixed-facility ORs revealed no gram-negative bacterial contamination prior to the
      opening of the modular OR and 5 weeks later. Bacterial aerosolization during
      surgery in a deployed fixed hospital revealed a mean gram-negative bacteria
      colony count of 12.8 colony-forming units (CFU)/dm(2)/h (standard deviation [SD],
      17.0) during surgeries and 6.5 CFU/dm(2)/h (SD, 7.5; [Formula: see text]) when
      the OR was not in use. CONCLUSION: This study demonstrates no significant gram
      negative bacilli colonization of modular and fixed-facility ORs or dirt and no
      significant aerosolization of these bacilli during surgical procedures. These
      results lend additional support to the role of nosocomial transmission of MDR
      pathogens or the colonization of the patient themselves prior to injury.

PMID- 22869265
TI  - Successful implementation of a window for routine antimicrobial prophylaxis
      shorter than that of the World Health Organization standard.
AB  - OBJECTIVE: To evaluate the feasibility of implementation of the refined window
      for routine antimicrobial prophylaxis (RAP) of 30-74 minutes before skin incision
      compared to the World Health Organization (WHO) standard of 0-60 minutes. DESIGN:
      Prospective study on timing of routine antimicrobial prophylaxis in 2 different
      time periods. SETTING: Tertiary referral university hospital with 30,000 surgical
      procedures per year. METHODS: In all consecutive vascular, visceral, and trauma
      procedures, the timing was prospectively recorded during a first time period of 2
      years (A; baseline) and a second period of 1 year (B; after intervention). An
      intensive intervention program was initiated after baseline. The primary outcome
      parameter was timing; the secondary outcome parameter was surgical site infection
      (SSI) rate in the subgroup of patients undergoing cholecystectomy/colon
      resection. RESULTS: During baseline time period A (3,836 procedures), RAP was
      administered 30-74 minutes before skin incision in 1,750 (41.0%) procedures;
      during time period B (1,537 procedures), it was administered in 914 (56.0%;
      [Formula: see text]). The subgroup analysis did not reveal a significant
      difference in SSI rate. CONCLUSIONS: This bundle of interventions resulted in a
      statistically significant improvement of timing of RAP even at a shortened window
      compared to the WHO standard.

PMID- 22869266
TI  - Infection control knowledge, attitudes, and practices among healthcare workers at
      Mulago Hospital, Kampala, Uganda.
AB  - OBJECTIVE: Effective implementation of infection control programs and adherence
      to standard precautions are challenging in resource-limited settings. The
      objective of this study was to describe infection control knowledge, attitudes,
      and practices among healthcare workers (HCWs) in Uganda. DESIGN: We conducted a
      survey of hospital employees who had direct contact with patients or their
      immediate environment. We also performed an environmental assessment of resource
      availability and utilization within hospital wards. SETTING: Surgical, medicine,
      and obstetrics wards at a national referral hospital in Kampala, Uganda.
      PARTICIPANTS: One hundred eighty-three randomly selected HCWs. RESULTS: Almost
      all HCWs knew to wash their hands, although nursing and support staff were less
      likely to perceive that HCWs' hands can be a vector of disease transmission. Hand
      washing was valued more as a means of self-protection than as a means to prevent
      patient-to-patient transmission, consistent with the prevailing belief that
      infection control was important for occupational safety. Sinks were not readily
      accessible, and soap at sinks was uncommon throughout the medicine and obstetrics
      wards but more commonly available in the surgery wards. Alcohol gel was rarely
      available. CONCLUSIONS: Changing infection control practices in developing
      countries will require a multifaceted approach that addresses resource
      availability, occupational safety, and local understanding and attitudes about
      infection control.

PMID- 22869267
TI  - Innovative approaches for understanding seasonal influenza vaccine declination in
      healthcare personnel support development of new campaign strategies.
AB  - OBJECTIVE: The main objectives of our study were to explore reasons for seasonal
      influenza vaccine acceptance and declination in employees of a large integrated
      healthcare system and to identify underlying constructs that influence acceptance
      versus declination. Secondary objectives were to determine whether vaccine
      acceptance varied by hospital location and to identify facility-level measures
      that explained variability. DESIGN: A national health promotion survey of
      employees was conducted that included items on vaccination in the 2009-2010
      influenza season. The survey was administered with two other institutional
      surveys in a stratified fashion: approximately 40% of participating employees
      were randomly assigned to complete the health promotion survey. SETTING: National
      single-payer healthcare system with 152 hospitals. PARTICIPANTS: Employees of the
      healthcare system in 2010 who responded to the survey. METHODS: Factor analysis
      was used to identify underlying constructs that influenced vaccine acceptance
      versus declination. Mean factor scores were examined in relation to demographic
      characteristics and occupation. Multilevel logistic regression models were used
      to determine whether vaccine acceptance varied by location and to identify
      facility-level measures that explained variability. RESULTS: Four factors were
      identified related to vaccine declination and were labeled as (1) "don't care,"
      (2) "don't want," (3) "don't believe," and (4) "don't know." Significant
      differences in mean factor scores existed by demographic characteristics and
      occupation. Vaccine acceptance varied by location, and vaccination rates in the
      previous year were an important facility-level predictor. CONCLUSIONS: Results
      should guide interventions that tailor messages on the basis of particular
      reasons for declination. Occupation-specific and culturally appropriate messaging
      should be considered. Continued efforts will be taken to better understand how
      workplace context influences vaccine acceptance.

PMID- 22869268
TI  - Casablanca redux: we are shocked that public reporting of rates of central line
      associated bloodstream infections are inaccurate.

PMID- 22869269
TI  - Prevention of central line-associated bloodstream infections in hemodialysis
      patients.
AB  - An increasing proportion of central line-associated bloodstream infections
      (CLABSIs) are seen in outpatient settings. Many of such infections are due to
      hemodialysis catheters (HD-CLABSIs). Such infections are associated with
      substantial morbidity, mortality, and excess healthcare costs. Patients who
      receive dialysis through a catheter are 2-3 times more likely to be hospitalized
      for infection and to die of septic complications than dialysis patients with
      grafts or fistulas. Prevention measures include minimizing the use of
      hemodialysis catheters, use of CLABSI prevention bundles for line insertion and
      maintenance, and application of antimicrobial ointment to the catheter exit site.
      Instillation into dialysis catheters of antimicrobial solutions that remain in
      the catheter lumen between dialyses (antimicrobial lock solutions) has been
      studied, but it is not yet standard practice in some dialysis units. At least 34
      studies have evaluated the impact of antimicrobial lock solutions on HD-CLABSI
      rates. Thirty-two (94%) of the 34 studies demonstrated reductions in HD-CLABSI
      rates among patients treated with antimicrobial lock solutions. Recent
      multicenter randomized controlled trials demonstrated that the use of such
      solutions resulted in significantly lower HD-CLABSI rates, even though such rates
      were low in control groups. The available evidence supports more routine use of
      antimicrobial lock solutions as an HD-CLABSI prevention measure in hemodialysis
      units.

PMID- 22869270
TI  - A qualitative assessment of a performance measure for reporting influenza
      vaccination rates among healthcare personnel.
AB  - To understand the feasibility of implementing a standardized performance measure
      for collecting and reporting influenza vaccination rates among healthcare
      personnel, qualitative, semistructured interviews were conducted with key
      informants in 32 healthcare facilities. Despite practical and logistical
      challenges to implementing the measure, respondents perceived clear benefits to
      its use.

PMID- 22869271
TI  - Air contamination around patients colonized with multidrug-resistant organisms.
AB  - Care-related infections are a major public health concern. Their transmission can
      be associated with environmental factors. This study looks at air contamination
      around 45 patients colonized with multidrug-resistant organisms (MDROs). We found
      that 30 hospital rooms (67%) were contaminated with MDRO species and 10 rooms
      (22%) were contaminated with at least 1 MDRO.

PMID- 22869272
TI  - Hospital flood preparedness: a survey of 15 provinces in central Thailand.

PMID- 22869273
TI  - Carbapenem-resistant enterobacteriaceae: a statewide survey of detection in
      Massachusetts hospitals.

PMID- 22869274
TI  - Active surveillance for methicillin-resistant Staphylococcus aureus including
      polymerase chain reaction-based screening prevents transmission in a dermatology
      ward.

PMID- 22869275
TI  - Using an intensified infection prevention intervention to control carbapenemase
      producing Enterobacteriaceae at a Thai center.

PMID- 22869276
TI  - Chlorhexidine is better than aqueous povidone iodine as skin antiseptic for
      preventing surgical site infections.

PMID- 22869277
TI  - Seasonal influenza vaccine compliance and use of declination forms.

PMID- 22869279
TI  - Vertebral osteonecrosis in an HIV-infected patient.
AB  - Vertebral osteonecrosis, also known as Kummell's disease, is a disorder resulting
      in non-consolidation of a vertebral fracture caused by ischaemia. The main
      differential diagnosis of vertebral osteonecrosis is osteoporotic vertebral
      fracture; however, the former is associated more frequently with severe pain and
      neurological complications. Although HIV-infected patients have an increased risk
      of developing osteonecrosis in peripheral locations and osteoporotic vertebral
      fractures, the occurrence of vertebral osteonecrosis has not been previously
      reported in any of the large series of HIV-associated osteonecrosis. Here, we
      report an HIV-infected patient who developed vertebral osteonecrosis with
      refractory pain and displayed rapid kyphotic deformity development during HAART.

PMID- 22869281
TI  - Atrial fibrillation: Electrophysiologists eagerly await independent CONFIRMation
      of improved method for ablation.

PMID- 22869280
TI  - Infections in pediatric postdiarrheal hemolytic uremic syndrome: factors
      associated with identifying shiga toxin-producing Escherichia coli.
AB  - OBJECTIVE: To describe pathogens identified through routine clinical practice and
      factors associated with identifying Shiga toxin-producing Escherichia coli (STEC)
      infection in patients with postdiarrheal hemolytic uremic syndrome (DHUS).
      DESIGN: Population-based active surveillance. SETTING: Hospitals in the FoodNet
      surveillance areas from 2000 through 2010. PARTICIPANTS: Children younger than 18
      years with DHUS. MAIN EXPOSURES: Testing for STEC and demographic and clinical
      characteristics. MAIN OUTCOME MEASURES: Percentage of patients with evidence of
      infection with likely HUS-causing agents and associations between exposures and
      evidence of STEC infection. RESULTS: Of 617 patients, 436 (70.7%) had evidence of
      infection with likely HUS-causing agents: STEC O157 (401 patients), non-O157 STEC
      (21 patients), O157 and non-O157 STEC (1 patient), Streptococcus pneumoniae (11
      patients), and other pathogens (2 patients). Among patients without
      microbiological evidence of STEC, 76.9% of those tested had serologic evidence of
      STEC infection. Children more likely to have evidence of STEC infections included
      those patients tested for STEC less than 4 days after diarrhea onset, 12 months
      or older (71.6% vs 27.8% if <12 months of age), with infections as part of an
      outbreak (94.3% vs 67.3%), with bloody diarrhea (77.2% vs 40.4%), with onset
      during June through September (76.9% vs 60.1%), with a leukocyte count greater
      than 18 000/MUL (to convert to *10(9)/L, multiply by 0.001) (75.7% vs 65.3%), or
      with only moderate anemia (hemoglobin 7.0 g/dL [to convert to grams per liter,
      multiply by 10] or hematocrit greater than 20% [to convert to a proportion of 1,
      multiply by 0.01]) (75.1% vs 66.3%). However, many of these associations were
      weaker among children with thorough STEC testing. CONCLUSIONS: Early stool
      collection for E coli O157 culture and Shiga toxin testing of all children with
      possible bacterial enteric infection will increase detection of STEC strains
      causing HUS. In the absence of microbiological evidence of STEC, serologic
      testing should be performed.

PMID- 22869282
TI  - The emerging role of amiodarone and dronedarone in Chagas disease.
AB  - Chagas disease has emerged as an important health problem in the Americas and,
      with globalization, in other parts of the world. Drug therapy for this parasitic
      infection has remained largely ineffective, especially in chronic stages of the
      disease. However, developments in experimental therapy might signal an important
      advance for the management of patients with Chagas disease. Herein, we review
      studies on the potential use of the benzofuran derivatives amiodarone and
      dronedarone in patients with Chagas disease. These agents have a dual role, not
      only as primary antiarrhythmic drugs, but also as antiparasitic agents. We
      believe that this 'kill two birds with one stone' approach represents a new
      tactic for the treatment of Chagas disease using currently approved drugs.

PMID- 22869283
TI  - Public health: Health risks of physical inactivity similar to smoking.

PMID- 22869284
TI  - Identification of positive yield QTL alleles from exotic soybean germplasm in two
      backcross populations.
AB  - Increasing seed yield is an important breeding goal of soybean [Glycine max (L.)
      Merr.] improvement efforts. Due to the small number of ancestors and subsequent
      breeding and selection, the genetic base of current soybean cultivars in North
      America is narrow. The objective of this study was to map quantitative trait loci
      (QTL) in two backcross populations developed using soybean plant introductions as
      donor parents. The first population included 116 BC(2)F(3)-derived lines
      developed using "Elgin" as the recurrent parent and PI 436684 as the donor parent
      (E population). The second population included 93 BC(3)F(3)-derived lines
      developed with "Williams 82" as the recurrent parent and PI 90566-1 as the donor
      parent (W population). The two populations were evaluated with 1,536 SNP markers
      and during 2 years for seed yield and other agronomic traits. Genotypic and
      phenotypic data were analyzed using the programs MapQTL and QTLNetwork to
      identify major QTL and epistatic QTL. In the E population, two yield QTL were
      identified by both MapQTL and QTLNetwork, and the PI 436684 alleles were
      associated with yield increases. In the W population, a QTL allele from PI 90566
      1 accounted for 30 % of the yield variation; however, the PI region was also
      associated with later maturity and shorter plant height. No epistasis for seed
      yield was identified in either population. No yield QTL was previously reported
      at the regions where these QTL map indicating that exotic germplasm can be a
      source of new alleles that can improve soybean yield.

PMID- 22869285
TI  - Preventing weight gain during adjuvant chemotherapy for breast cancer: a dietary
      intervention study.
AB  - Adjuvant chemotherapy significantly decreases recurrences and improves survival
      in women with early breast cancer (BC). However, the side effects of chemotherapy
      include weight gain, which is associated with poorer prognosis. We have
      previously demonstrated that by means of a comprehensive dietary modification
      which aims at lowering insulin levels it is possible to reduce body weight and
      decrease the bioavailability of insulin, sex hormones and the growth factors
      linked to BC risk and prognosis. We are now going to present a randomized
      controlled study of adjuvant diet in BC patients undergoing chemotherapy. The
      diet was designed to prevent weight gain during chemotherapy treatment. Women of
      any age, operated for invasive BC, scheduled for adjuvant chemotherapy and
      without evidence of distant metastases, were randomized into a dietary
      intervention group and a control group. The intervention implied changing their
      usual diet for the whole duration of chemotherapy, following cooking classes and
      having lunch or dinner at the study centre at least twice per week. 96 BC
      patients were included in the study. The women in the intervention group showed a
      significant reduction in their body weight (2.9 kg on average), compared with the
      controls. They also significantly reduced body fat mass, waist and hip
      circumferences, biceps, underscapular and suprailiac skinfolds, compared with the
      women in the control group. Our results support the hypothesis that dietary
      intervention during adjuvant chemotherapy for BC is feasible and may prevent
      weight gain.

PMID- 22869286
TI  - [Tongue retraining and occlusal stability in a young adult. Case report].
AB  - The clinical observation describes the case of a 20-year-old woman who has
      consulted for aesthetic and functional reasons. She presents a skeletal class III
      normodivergent, an occlusal class III with a lower proalveoli quite marked. In
      addition, a lingual dysfunction which manifests itself by important anterior
      diastema and dento-dental disharmony at the upper jaw complicates the case. The
      undertaken therapeutic project starts with a first step of a lingual praxis
      rehabilitation, followed by an orthodontic step and upper lateral incisors
      plasty. The purpose of those results is the evaluation of the stability two years
      later, which was reported positive.

PMID- 22869287
TI  - Production of transgenic goats expressing human coagulation factor IX in the
      mammary glands after nuclear transfer using transfected fetal fibroblast cells.
AB  - There are growing numbers of recombinant proteins that have been expressed in
      milk. Thus one can consider the placement of any gene of interest under the
      control of the regulatory elements of a milk protein gene in a dairy farm animal.
      Among the transgene introducing techniques, only nuclear transfer (NT) allows 100
      % efficiency and bypasses the mosaicism associated with counterpart techniques.
      In this study, in an attempt to produce a transgenic goat carrying the human
      coagulation factor IX (hFIX) transgene, goat fetal fibroblasts were
      electroporated with a linearized marker-free construct in which the transgene was
      juxtaposed to beta-casein promoter designed to secret the recombinant protein in
      goat milk. Two different lines of transfected cells were used as donors for NT to
      enucleated oocytes. Two transgenic goats were liveborn. DNA sequencing of the
      corresponding transgene locus confirmed authenticity of the cloning procedure and
      the complementary experiments on the whey demonstrated expression of human factor
      IX in the milk of transgenic goats. In conclusion, our study has provided the
      groundwork for a prosperous and promising approach for large-scale production and
      therapeutic application of hFIX expressed in transgenic goats.

PMID- 22869288
TI  - Comparison of Agrobacterium and particle bombardment using whole plasmid or
      minimal cassette for production of high-expressing, low-copy transgenic plants.
AB  - Transgene integration complexity in the recipient genome can be an important
      determinant of transgene expression and field performance in transgenic crops. We
      provide the first direct comparison of Agrobacterium-mediated transformation
      (AMT) and particle bombardment using whole plasmid (WP) and excised minimal
      cassettes (MC), for transformation efficiency, transgene integration complexity
      and transgene expression in plants. To enable direct comparison, a selectable
      marker and a luciferase reporter gene were linked in identical configurations in
      plasmids suitable for AMT or direct gene transfer into sugarcane. Transformation
      efficiencies were similar between WP and MC when equal molar DNA quantities were
      delivered. When the MC concentration was reduced from 66 to 6.6 ng per shot,
      transformation efficiency dropped fourfold, to a level equivalent with AMT in
      amenable genotype Q117. The highest proportion of transformants combining low
      copy number (estimated below two integrated copies by qPCR) with expression of
      the non-selected reporter gene was obtained using AMT (55 %) or MC at low DNA
      concentration (30 %). In sugarcane, both of these methods yielded high
      expressing, single-copy transgenic plant lines at a workable efficiency for
      practical plant improvement; but AMT is currently limited to a few amenable
      genotypes. These methods are best coupled with rapid early screens for desired
      molecular characteristics of transformants, e.g. PCR screens for low copy number
      and/or transcription of the gene of practical interest.

PMID- 22869289
TI  - PSA reconsidered.

PMID- 22869290
TI  - Ivermectin (Sklice) topical lotion for head lice.

PMID- 22869291
TI  - Tablet splitting.

PMID- 22869292
TI  - In brief: Truvada for HIV prevention.

PMID- 22869293
TI  - Modulation of action potential trains in rabbit saphenous nerve unmyelinated
      fibers.
AB  - Usually, the main axon is assumed to faithfully conduct action potentials (APs).
      Recent data have indicated that neural processing can occur along the axonal
      path. However, the patterns and mechanisms of temporal coding are not clear. In
      the present study, single fiber recording was used to analyze activity-dependent
      modulation of AP trains in the main axons of C fibers in the rabbit saphenous
      nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of
      20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals
      (ISIs) for these trains were compared to the input interstimulus intervals. Three
      basic types of C fibers were observed in response to repeated stimuli: first, the
      ISI between the first and second AP (ISI1-2) of type 1 was longer than the
      interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations
      around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited
      shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive
      potassium and hyperpolarization-activated cation currents were involved in the
      modulation of ISI1-2 of train pulses. These data provide new evidence that
      multiple modes of neural conduction can occur along the main axons of C fibers.

PMID- 22869294
TI  - Effect of hepatitis C treatment on CD4+ T-cell counts and the risk of death in
      HIV-HCV-coinfected patients: the COHERE collaboration.
AB  - BACKGROUND: The short- and long-term effects of anti-hepatitis C treatment on
      mortality in the HIV-HCV-coinfected population have not been evaluated in
      observational cohorts. Such evaluations must use methods that allow for time
      varying prognostic factors that both predict treatment and are affected by prior
      treatment. We aimed to study immunological changes in HIV-HCV-coinfected
      individuals during HCV treatment and to estimate the effect of HCV-treatment on
      mortality. METHODS: Patients were included if they were aged >=16 years, were HIV
      HCV-coinfected and were enrolled in the COHERE cohort. Data were pooled within
      COHERE in December 2009 in EuroCoord. Random-effects models were used to model
      immunological changes during HCV treatment. Marginal structural models were used
      to estimate the effect of HCV treatment on mortality, allowing for time-dependent
      confounders affected by prior treatment. RESULTS: In total, 780/6,433 (12%) HIV
      HCV-coinfected patients initiated HCV treatment (interferon [IFN] and ribavirin
      n=692, IFN alone n=88). CD4(+) T-cell counts decreased during the first 12 weeks
      of treatment (P<0.0001) and stabilized from week 24 onwards. The estimated
      mortality hazard ratio for comparing HCV-treated with -untreated individuals was
      0.72 (95% CI 0.43, 1.21). The estimated hazard ratio for liver-related death was
      0.57 (95% CI 0.21, 1.55). CONCLUSIONS: Despite its effect in reducing CD4(+) T
      cell counts, the effect of HCV treatment on mortality was in the direction of
      benefit and our results excluded a substantial increase in mortality. Such
      benefit may be related to a lower risk of liver-related death. New HCV treatment
      strategies might contribute to a further reduction in mortality.

PMID- 22869295
TI  - Virtual fragment screening: exploration of MM-PBSA re-scoring.
AB  - An NMR fragment screening dataset with known binders and decoys was used to
      evaluate the ability of docking and re-scoring methods to identify fragment
      binders. Re-scoring docked poses using the Molecular Mechanics Poisson-Boltzmann
      Surface Area (MM-PBSA) implicit solvent model identifies additional active
      fragments relative to either docking or random fragment screening alone. Early
      enrichment, which is clearly most important in practice for selecting relatively
      small sets of compounds for experimental testing, is improved by MM-PBSA re
      scoring. In addition, the value in MM-PBSA re-scoring of docked poses for virtual
      screening may be in lessening the effect of the variation in the protein complex
      structure used.

PMID- 22869296
TI  - Targeted multiplex imaging mass spectrometry with single chain fragment variable
      (scfv) recombinant antibodies.
AB  - Recombinant scfv antibodies specific for CYP1A1 and CYP1B1 P450 enzymes were
      combined with targeted imaging mass spectrometry to simultaneously detect the
      P450 enzymes present in archived, paraffin-embedded, human breast cancer tissue
      sections. By using CYP1A1 and CYP1B1 specific scfv, each coupled to a unique
      reporter molecule (i.e., a mass tag) it was possible to simultaneously detect
      multiple antigens within a single tissue sample with high sensitivity and
      specificity using mass spectrometry. The capability of imaging multiple antigens
      at the same time is a significant advance that overcomes technical barriers
      encountered when using present day approaches to develop assays that can
      simultaneously detect more than a single antigen in the same tissue sample.

PMID- 22869297
TI  - Electron transfer dissociation mass spectrometry of hemoglobin on clinical
      samples.
AB  - A mass spectrometry-based assay combining the specificity of selected reaction
      monitoring and the protein ion activation capabilities of electron transfer
      dissociation was developed and employed for the rapid identification of
      hemoglobin variants from whole blood without previous proteolytic cleavage. The
      analysis was performed in a robust ion trap mass spectrometer operating at
      nominal mass accuracy and resolution. Subtle differences in globin sequences,
      resulting with mass shifts of about one Da, can be unambiguously identified.
      These results suggest that mass spectrometry analysis of entire proteins using
      electron transfer dissociation can be employed on clinical samples in a workflow
      compatible with diagnostic applications.

PMID- 22869298
TI  - Quantifying protein-ligand binding constants using electrospray ionization mass
      spectrometry: a systematic binding affinity study of a series of hydrophobically
      modified trypsin inhibitors.
AB  - NanoESI-MS is used for determining binding strengths of trypsin in complex with
      two different series of five congeneric inhibitors, whose binding affinity in
      solution depends on the size of the P3 substituent. The ligands of the first
      series contain a 4-amidinobenzylamide as P1 residue, and form a tight complex
      with trypsin. The inhibitors of the second series have a 2-aminomethyl-5-chloro
      benzylamide as P1 group, and represent a model system for weak binders. The five
      different inhibitors of each group are based on the same scaffold and differ only
      in the length of the hydrophobic side chain of their P3 residue, which modulates
      the interactions in the S3/4 binding pocket of trypsin. The dissociation
      constants (K(D)) for high affinity ligands investigated by nanoESI-MS ranges from
      15 nM to 450 nM and decreases with larger hydrophobic P3 side chains. Collision
      induced dissociation (CID) experiments of five trypsin and benzamidine-based
      complexes show a correlation between trends in K(D) and gas-phase stability. For
      the second inhibitor series we could show that the effect of imidazole, a small
      stabilizing additive, can avoid the dissociation of the complex ions and as a
      result increases the relative abundance of weakly bound complexes. Here the K(D)
      values ranging from 2.9 to 17.6 MUM, some 1-2 orders of magnitude lower than the
      first series. For both ligand series, the dissociation constants (K(D)) measured
      via nanoESI-MS were compared with kinetic inhibition constants (K(i)) in
      solution.

PMID- 22869299
TI  - Antihypertensive drugs and lip cancer in non-Hispanic whites.
AB  - BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we
      noted an association between lip cancer risk and the photosensitizing
      antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we
      further characterized the risk of lip cancer associated with these and other
      commonly used antihypertensive drugs. METHODS: In a comprehensive medical care
      program, we evaluated prescriptions dispensed and cancer occurrence from August
      1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases)
      and 22,904 comparison individuals (controls) matched for age, sex, and cohort
      year of entry in the susceptible group, non-Hispanic whites. We determined use,
      at least 2 years before diagnosis or control index date, of the commonly
      prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with
      triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium
      channel blocker nifedipine, and the beta-adrenergic blocker atenolol, the only
      nonphotosensitizer agent studied. We analyzed the use of each drug exclusively
      and regardless of use of the others, and focused on duration of use. Conditional
      logistic regression was used for analysis of matched case-control sets, with
      control for cigarette smoking. RESULTS: At least a 5-year supply of a drug
      yielded the following odds ratios (95% CIs), respectively, compared with no use:
      hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82
      (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and
      atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio
      for atenolol was reduced to 0.54 (0.07-4.08). CONCLUSION: These data support an
      increased risk of lip cancer in non-Hispanic whites receiving treatment for
      hypertension with long-term use of photosensitizing drugs.

PMID- 22869300
TI  - Chondrogenic differentiation of amniotic fluid stem cells and their potential for
      regenerative therapy.
AB  - Chronic articular cartilage defects are the most common disabling conditions of
      humans in the western world. The incidence for cartilage defects is increasing
      with age and the most prominent risk factors are overweight and sports associated
      overloading. Damage of articular cartilage frequently leads to osteoarthritis due
      to the aneural and avascular nature of articular cartilage, which impairs
      regeneration and repair. Hence, patients affected by cartilage defects will
      benefit from a cell-based transplantation strategy. Autologous chondrocytes,
      mesenchymal stem cells and embryonic stem cells are suitable donor cells for
      regeneration approaches and most recently the discovery of amniotic fluid stem
      cells has opened a plethora of new therapeutic options. It is the aim of this
      review to summarize recent advances in the use of amniotic fluid stem cells as
      novel cell sources for the treatment of articular cartilage defects. Molecular
      aspects of articular cartilage formation as well as degeneration are summarized
      and the role of growth factor triggered signaling pathways, scaffolds, hypoxia
      and autophagy during the process of chondrogenic differentiation are discussed.

PMID- 22869302
TI  - Development of a duration threshold for modulating evoked neuronal responses
      after nerve root compression injury.
AB  - Cervical nerve roots are susceptible to compression injuries of various
      durations. The duration of an  applied compression has been shown to contribute
      to both the onset of persistent pain and also the degree of spinal cellular and 
      molecular responses related to nociception. This study investigated the
      relationship between peripherally-evoked activity in  spinal cord neurons during
      a root compression and the resulting development of axonal damage. Electrically
      evoked spikes were  measured in the spinal cord as a function of time during and
      after (post-compression) a 15 minute compression of the C7 nerve  root.
      Compression to the root significantly (p=0.035) reduced the number of spikes that
      were evoked over time relative to sham.  The critical time for compression to
      maximally reduce evoked spikes was 6.6+/-3.0 minutes. A second study measured the
      post-  compression evoked neuronal activity following compression applied for a
      shorter, sub-threshold time (three minutes). Ten  minutes after compression was
      removed, the discharge rate remained significantly (p=0.018) less than baseline
      by 58+/-25%  relative to sham after the 15 minute compression, but returned to
      within 3+/-33% of baseline after the three minute compression.  Axonal damage was
      evident in the nerve root at day seven after nerve root compression only after a
      15 minute compression.  These studies demonstrate that even a transient
      mechanical insult to the nerve root is sufficient to induce sustained neuronal 
      dysfunction and axonal pathology associated with pain, and results provide
      support that such minor neural tissue traumas can  actually induce long-lasting
      functional deficits.

PMID- 22869301
TI  - Brainstem auditory evoked potentials suggest a role for the ventral cochlear
      nucleus in tinnitus.
AB  - Numerous studies have demonstrated elevated spontaneous and sound-evoked
      brainstem activity in animal models of tinnitus, but data on brainstem function
      in people with this common clinical condition are sparse. Here, auditory nerve
      and brainstem function in response to sound was assessed via auditory brainstem
      responses (ABR) in humans with tinnitus and without. Tinnitus subjects showed
      reduced wave I amplitude (indicating reduced auditory nerve activity) but
      enhanced wave V (reflecting elevated input to the inferior colliculi) compared
      with non-tinnitus subjects matched in age, sex, and pure-tone threshold. The
      transformation from reduced peripheral activity to central hyperactivity in the
      tinnitus group was especially apparent in the V/I and III/I amplitude ratios.
      Compared with a third cohort of younger, non-tinnitus subjects, both tinnitus,
      and matched, non-tinnitus groups showed elevated thresholds above 4 kHz and
      reduced wave I amplitude, indicating that the differences between tinnitus and
      matched non-tinnitus subjects occurred against a backdrop of shared peripheral
      dysfunction that, while not tinnitus specific, cannot be discounted as a factor
      in tinnitus development. Animal lesion and human neuroanatomical data combine to
      indicate that waves III and V in humans reflect activity in a pathway originating
      in the ventral cochlear nucleus (VCN) and with spherical bushy cells (SBC) in
      particular. We conclude that the elevated III/I and V/I amplitude ratios in
      tinnitus subjects reflect disproportionately high activity in the SBC pathway for
      a given amount of peripheral input. The results imply a role for the VCN in
      tinnitus and suggest the SBC pathway as a target for tinnitus treatment.

PMID- 22869303
TI  - Injury predictors for traumatic axonal injury in a rodent head impact
      acceleration model.
AB  - A modified Marmarou impact acceleration injury model was developed to study the
      kinematics of the rat head to quantify traumatic axonal injury (TAI) in the
      corpus callosum (CC) and brainstem pyramidal tract (Py), to determine injury
      predictors and to establish injury thresholds for severe TAI. Thirty-one
      anesthetized male Sprague-Dawley rats (392+/-13 grams) were impacted using a
      modified impact acceleration injury device from 2.25 m and 1.25 m heights. Beta
      amyloid precursor protein (beta-APP) immunocytochemistry was used to assess and
      quantify axonal changes in CC and Py. Over 600 injury maps in CC and Py were
      constructed in the 31 impacted rats. TAI distribution along the rostro-caudal
      direction in CC and Py was determined. Linear and angular responses of the rat
      head were monitored and measured in vivo with an attached accelerometer and
      angular rate sensor, and were correlated to TAI data. Logistic regression
      analysis suggested that the occurrence of severe TAI in CC was best predicted by
      average linear acceleration, followed by power and time to surface righting. The
      combination of average linear acceleration and time to surface righting showed an
      improved predictive result. In Py, severe TAI was best predicted by time to
      surface righting, followed by peak and average angular velocity. When both CC and
      Py were combined, power was the best predictor, and the combined average linear
      acceleration and average angular velocity was also found to have good injury
      predictive ability. Receiver operator characteristic curves were used to assess
      the predictive power of individual and paired injury predictors. TAI tolerance
      curves were also proposed in this study.

PMID- 22869304
TI  - Development of head injury assessment reference values based on NASA injury
      modeling.
AB  - NASA is developing a new crewed vehicle and desires a lower risk of injury
      compared to automotive or  commercial aviation. Through an agreement with the
      National Association of Stock Car Auto Racing, Inc. (NASCAR(r)), an  analysis of
      NASCAR impacts was performed to develop new injury assessment reference values
      (IARV) that may be more  relevant to NASA's context of vehicle landing
      operations. Head IARVs associated with race car impacts were investigated by 
      analyzing all NASCAR recorded impact data for the 2002-2008 race seasons. From
      the 4015 impact files, 274 impacts were  selected for numerical simulation using
      a custom NASCAR restraint system and Hybrid III 50th percentile male Finite
      Element  Model (FEM) in LS-DYNA. Head injury occurred in 27 of the 274 selected
      impacts, and all of the head injuries were mild  concussions with or without
      brief loss of consciousness. The 247 noninjury impacts selected were
      representative of the range of  crash dynamics present in the total set of
      impacts. The probability of head injury was estimated for each metric using an
      ordered  probit regression analysis. Four metrics had good correlation with the
      head injury data: head resultant acceleration, head change  in velocity, HIC 15,
      and HIC 36. For a 5% risk of AIS>=1/AIS>=2 head injuries, the following IARVs
      were found: 121.3/133.2 G  (head resultant acceleration), 20.3/22.0 m/s (head
      change in velocity), 1,156/1,347 (HIC 15), and 1,152/1,342 (HIC 36) 
      respectively. Based on the results of this study, further analysis of additional
      datasets is recommended before applying these  results to future NASA vehicles.

PMID- 22869305
TI  - Simulation of human head response to impact loading using newly developed
      biofidelic material models for brain tissue.
AB  - Brain tissue is known to exhibit regional and directional variations in its
      mechanical response to external loads.  Material models traditionally used to
      simulate brain tissue deformation in the human head have been primarily region 
      independent and limited to isotropic and linear viscoelastic. The primary goal of
      this research is to develop a biofidelic material  model for brain tissue by
      accounting for the underlying microstructure of the material. A computational and
      analytical approach  was undertaken in our attempt to develop a more realistic
      material model. Based on the microstructure observed at the neuron  level, a
      mesoscale model was developed which included neurons, glial cells and Cerebro
      Spinal Fluid (CSF). A semi-analytical  model was first developed using a
      simplified geometry accounting for separate fiber and matrix (fluid) behavior of
      the medium.  A second computational model was also constructed by developing a
      representative volume element (RVE) of brain tissue that  includes the neurons,
      glial cells and CSF. Diffusion Tensor Imaging (DTI) was also utilized to capture
      anisotropy and directional  dependence of the tissue on the continuum scale.
      Using the aforementioned material models, computational simulations were 
      performed to predict the mechanical response of the brain tissue when subjected
      to a non-penetrating, impact load.

PMID- 22869306
TI  - Investigation on occupant ejection in high severity rear impact based on post
      mortem human subject sled tests.
AB  - Occupant protection in rear impact involves two competing challenges. On one
      hand, allowing a deformation of  the seat would act as an energy absorber in low
      severity impacts and would consequently decrease the risk of neck injuries. 
      However, on the other hand, large deformations of the seat may increase the
      likelihood of occupant ejection in high severity  cases. Green et al. 1987
      analyzed a total of 919 accidents in Great Britain. They found that occupant
      ejection resulted in a risk of  severe injuries and fatalities between 3.6 and
      4.5 times higher than those cases where no ejection was observed. The sample 
      included single front, side and rear impacts as well as multiple impacts and
      rollover. The rate of belt use in the sample was 50%.  While this analysis
      included all forms of impact scenarios, nevertheless, it highlights the relative
      injury severity of occupant  ejection.  Extensive literature search has found no
      full-scale rear impact tests involving Post Mortem Human Subjects (PMHS)
      conducted  in a laboratory environment and resulting in ejection.  This paper
      describes a total of 10 sled tests conducted on 3 belted PMHS using a simplified
      seat design composed of rigid plates  assembled such that the angular and linear
      stiffness of the seatback (including the foam) was modeled. The initial angular 
      position and the range of motion of the seatback, the size of the PMHS, the slack
      length of the seatbelt, the angular stiffness of  the seatback, and the use of
      headrest were varied in the test matrix while the pulse was kept constant
      (triangular acceleration with  a peak of 17 G at 30 ms and a duration of 95 ms). 
      In the test series, the tests were not run randomly but the likelihood of
      occupant ejection was increased systematically until  ejection occurred.  PMHS
      seat ejection was observed only for the 95th percentile, initially positioned
      with a seatback angle relative to the vertical  equal to 22 degrees , a range of
      seatback angular motion equal to 44 degrees  and no headrest. Repeating the test
      under the same conditions but  with the pretentionner fired did not prevent the
      ejection. In addition, the 50th percentile belted specimen were not observed to 
      sustain rearward seat ejection under realistic conditions including the use of
      head-rest.

PMID- 22869307
TI  - Head impact mechanisms of a child occupant seated in a child restraint system as
      determined by impact testing.
AB  - In side collision accidents, the head is the most frequently injured body region
      for child occupants seated in a  child restraint system (CRS). Accident analyses
      show that a child's head can move out of the CRS shell, make hard contact with 
      the vehicle interior, and thus sustain serious injuries. In order to improve
      child head protection in side collisions, it is necessary to  understand the
      injury mechanism of a child in the CRS whose head makes contact with the vehicle
      interior. In this research, an  SUV-to-car oblique side crash test was conducted
      to reconstruct such head contacts. A Q3s child dummy was seated in a CRS in  the
      rear seat of the target car. The Q3s child dummy's head moved out beyond the CRS
      side wing, moved laterally, and made  contact with the side window glass and the
      doorsill. It was demonstrated that the hard head contact, which produced a high
      HIC  value, could occur in side collisions. A series of sled tests was carried
      out to reproduce the dummy kinematic behavior observed  in the SUV-to-car crash
      test, and the sled test conditions such as sled angle, ECE seat slant angle and
      velocity-time history that  duplicated the kinematic behavior were determined. A
      parametric study also was conducted with the sled tests; and it was found  that
      the impact angle, harness slack, chest clip, and the CRS side wing shape affected
      the torso motion and head contact with the  vehicle interior.

PMID- 22869308
TI  - Assessment of a three-point restraint system with a pre-tensioned lap belt and an
      inflatable, force-limited shoulder belt.
AB  - This study investigates the performance of a 3-point restraint system
      incorporating an inflatable shoulder belt  with a nominal 2.5-kN load limiter and
      a non-inflatable lap belt with a pretensioner (the "Airbelt"). Frontal impacts
      with PMHS  in a rear seat environment are presented and the Airbelt system is
      contrasted with an earlier 3-point system with inflatable lap and  shoulder belts
      but no load-limiter or pretensioners, which was evaluated with human volunteers
      in the 1970s but not fully  reported in the open literature (the "Inflataband").
      Key differences between the systems include downward pelvic motion and  torso
      recline with the Inflataband, while the pelvis moved almost horizontally and the
      torso pitched forward with the Airbelt.  One result of these kinematic
      differences was an overall more biomechanically favorable restraint loading but
      greater maximum  forward head excursion with the Airbelt. The Airbelt is shown to
      generate generally lower head, neck, and thoracic injury  metrics and PMHS trauma
      than other, non-inflatable rear-seat restraint concepts (viz., a standard 3-point
      belt and a pre-tensioned  shoulder belt with a progressive load limiter). Further
      study is needed to evaluate the Airbelt system for different size occupants 
      (e.g., children), non-frontal impact vectors, and for out-of-position occupants
      and to allow the results with this particular system  to be generalized to a
      broader range of Airbelt designs.

PMID- 22869309
TI  - Biomechanical assessment of a rear-seat inflatable seatbelt in frontal impacts.
AB  - This study evaluated the biomechanical performance of a rear-seat inflatable
      seatbelt system and compared it to  that of a 3-point seatbelt system, which has
      a long history of good real-world performance. Frontal-impact sled tests were 
      conducted with Hybrid III anthropomorphic test devices (ATDs) and with post
      mortem human subjects (PMHS) using both  restraint systems and a generic rear
      seat configuration. Results from these tests demonstrated: a) reduction in
      forward head  excursion with the inflatable seatbelt system when compared to that
      of a 3-point seatbelt and; b) a reduction in ATD and PMHS  peak chest deflections
      and the number of PMHS rib fractures with the inflatable seatbelt system and c) a
      reduction in PMHS  cervical-spine injuries, due to the interaction of the chin
      with the inflated shoulder belt. These results suggest that an inflatable 
      seatbelt system will offer additional benefits to some occupants in the rear
      seats. Further research is needed to assess the field  effectiveness, customer
      comfort and acceptance and change in the belt usage rate with the inflatable
      seatbelt system.

PMID- 22869310
TI  - Study of rib fracture mechanisms based on the rib strain profiles in side and
      forward oblique impact.
AB  - Rib fractures constitute a good indication of severity as there are the most
      frequent type of AIS3+ chest injuries.  In 2008, Trosseille et al. showed a
      promising methodology to exhibit the rib fracture mechanisms, using strain gauges
      glued on  the ribs of Post-Mortem Human Subjects (PMHS) and developing a specific
      signal analysis. In 2009, they published the results of  static airbag tests
      performed on 50th percentile male PMHS at different distances and angles (pure
      lateral and 30 degrees forward  oblique direction).  To complete these already
      published data, a set of 8 PMHS lateral and oblique impactor tests were performed
      with the same  methodology. The rib cages were instrumented with more than 100
      strain gauges on the ribs, cartilage and sternum. A 23.4 kg  impactor was
      propelled at 4.3 or 6.7 m/s. The forces applied onto the PMHS at 4.3 m/s ranged
      from 1.6 kN to 1.9 kN and the  injuries varied from 4 to 13 rib fractures. At 6.7
      m/s, the forces applied onto the PMHS ranged from 2.6 kN to 4 kN and the 
      injuries varied from 9 to 16 rib fractures.  The results of 24 tests from
      Trosseille et al. 2008 and 2009 and from the current study were processed in the
      same way and  analyzed together. The time and location of the fractures were
      determined for each test and a ribcage fracture scenario was  defined for each
      configuration. Strain profile corridors were built for pure lateral and forward
      oblique impacts, in the case of a  rigid impact (impactor) or for an airbag
      loading. They can be used to assess the human body model biofidelity and the
      validation  of rib fracture mechanisms in these models. Based on these corridors,
      the effects of the severity, the impact angle and the loading  system on rib
      strain profiles were analyzed and are presented in this paper.

PMID- 22869311
TI  - Evaluation of injury criteria for the prediction of commotio cordis from lacrosse
      ball impacts.
AB  - Commotio Cordis (CC) is the second leading cause of mortality in youth sports.
      Impacts occurring directly over the left ventricle (LV) during a vulnerable
      period of the cardiac cycle can cause ventricular fibrillation (VF), which
      results in CC. In order to better understand the pathophysiology of CC, and
      develop a mechanical model for CC, appropriate injury criteria need to be
      developed. This effort consisted of impacts to seventeen juvenile porcine
      specimens (mass 21-45 kg). Impacts were delivered over the cardiac silhouette
      during the venerable period of the cardiac cycle. Four impact speeds were used:
      13.4, 17.9, 22.4, and 26.8 m/s. The impactor was a lacrosse ball on an aluminum
      shaft instrumented with an accelerometer (mass 188 g-215 g). The impacts were
      recorded using high-speed video. LV pressure was measured with a catheter.
      Univariate binary logistic regression analyses were performed to evaluate the
      predictive ability of ten injury criteria. A total of 187 impacts were used in
      the analysis. The criteria were evaluated on their predictive ability based on
      Somers' D (D) and Goodman-Kruskal gamma (gamma). Injury risk functions were
      created for all criteria using a 2-parameter Weibull distribution using survival
      analysis. The best criteria for predicting CC were impact force (D=0.52, and
      gamma=0.52) force*compression (D=0.49, and gamma=0.49), and impact power (D=0.49,
      and gamma=0.49). All of these criteria proved significant in predicting the
      probability of CC from projectile impacts in youth sports (p<0.01). Force proved
      to be the most predictive of the ten criteria evaluated.

PMID- 22869312
TI  - Response of PMHS to high- and low-speed oblique and lateral pneumatic ram
      impacts.
AB  - In ISO Technical Report 9790 (1999) normalized lateral and oblique thoracic force
      time responses of PMHS subjected to blunt pendulum impacts at 4.3 m/s were deemed
      sufficiently similar to be grouped together in a single biomechanical response
      corridor. Shaw et al. (2006) presented results of paired oblique and lateral
      thoracic pneumatic ram impact tests to opposite sides of seven PMHS at sub
      injurious speed (2.5 m/s). Normalized responses showed that oblique impacts
      resulted in more deflection and less force, whereas lateral impacts resulted in
      less deflection and more force. This study presents results of oblique and
      lateral thoracic impacts to PMHS at higher speeds (4.5 and 5.5 m/s) to assess
      whether lateral relative to oblique responses are different as observed by Shaw
      et al. or similar as observed by ISO. Twelve PMHS were impacted by a 23 kg
      pneumatic ram with a 152.4 mmx304.8 mm rectangular face plate at the level of the
      xyphoid process in either the pure lateral or 30 degrees  anterior-to-lateral
      oblique direction. Because these tests were potentially injurious, only one test
      per subject was conducted. Normalized responses demonstrate similar
      characteristics for both lateral and oblique impacts, indicating that it may be
      reasonable to combine lateral and oblique responses together at these higher
      speeds to define characteristic PMHS response as was done by ISO. The small
      number of tests conducted indicates that less chest compression may be required
      to obtain serious thoracic injury in oblique impacts as compared to lateral
      impacts at speeds of 4.5 or 5.5 m/s.

PMID- 22869313
TI  - Pressure-based abdominal injury criteria using isolated liver and full-body post
      mortem human subject impact tests.
AB  - Liver trauma research suggests that rapidly increasing internal pressure plays a
      role in liver injury. Previous  work has shown a correlation between pressure and
      liver injury in pressurized ex vivo human livers when subjected to blunt 
      impacts. The purpose of this study was to extend the investigation of this
      relationship between pressure and liver injury by  testing full-body post-mortem
      human surrogates (PMHS). Pressure-related variables were compared with one
      another and  also to previously proposed biomechanical predictors of abdominal
      injury. Ten PMHS were tested. The abdominal vessels  were pressurized to
      physiological levels using saline, and a pneumatic ram impacted the right side of
      the specimen ribcage at  a nominal velocity of 7.0 m/s. Specimens were subjected
      to either lateral (n = 5) or oblique (n = 5) impacts, and the impact-  induced
      pressures were measured by transducers inserted into the hepatic veins and
      inferior vena cava. The liver injuries  observed were similar to those documented
      in the Crash Injury Research Engineering Network (CIREN) trauma database.  Using
      binary logistic regression to develop injury risk functions, it was determined
      the peak rate of pressure change (Pmax)  was a statistically significant
      predictor of AIS >= 3 liver injury for both the PMHS and ex vivo testing. This
      suggests that  Pmax is a good predictor of liver injury regardless of the impact
      boundary conditions.

PMID- 22869314
TI  - Region-specific deflection responses of WorldSID and ES2-re devices in pure
      lateral and oblique side impacts.
AB  - The objective of this study was to determine region-specific deflection responses
      of the WorldSID and ES2 -re  devices under pure lateral and oblique side impact
      loading. A modular, anthropometry-specific load wall was used. It consisted  of
      the Shoulder, Thorax, Abdomen, superior Pelvis, and inferior Pelvis plates,
      termed the STAPP load wall design. The two  devices were positioned upright on
      the platform of a bench seat, and sled tests were conducted at 3.4, 6.7, and 7.5
      m/s. Two  chestbands were used on each dummy at the thoracic and abdominal
      regions. Internal sensors were also used. Effective peak  deflections were
      obtained from the chestband contours. Based on the preselected lateral-most
      point/location on the pretest  contour, "internal sensor-type" peak deflections
      were also obtained using chestband contours. In addition, peak deflection data 
      were obtained from internal sensor records. In oblique tests, the mean "IR-TRACC
      type" peak deflections in the WorldSID  device were 40 to 80% of effective peak
      deflections, whereas the mean "potentiometer-type" peak deflections in the ES2
      device  were 7 to 50%. The WorldSID device appears to better mimic region 
      specific responses to oblique loading than the ES2-re  device, likely due to the
      differences in its des ign of the thoracic and abdominal regions. While the
      lateral -most point  corresponding to the current 1D IR-TRACC location was found
      to replicate the pure lateral response, it was found to be less than  optimal to
      track oblique loading. Although a laterally positioned sensor provides lower peak
      deflections in oblique loading, the  addition of an angle-measuring sensor should
      allow modulating the translational metric for this mode. From this perspective,
      it  may be worthwhile to use a 2D IR-TRACC or an optical sensor to verify these
      findings without chestband measures. Such an  analysis has the potential to
      modify thoracic and abdominal injury criteria to account for obliqueness.

PMID- 22869315
TI  - Comparison of Hybrid III and THOR dummies in paired small overlap tests.
AB  - The Insurance Institute for Highway Safety (IIHS) is investigating small overlap
      crash test procedures for a  possible consumer information program. Analysis of
      real-world small overlap crashes found a strong relationship between serious 
      head and chest injuries and occupant compartment intrusion. The main sources of
      serious head injuries were from the A-pillar,  dash panel, or door structure,
      suggesting head trajectories forward and outboard possibly bypassing the airbag.
      Chest injuries  mainly were from steering wheel intrusion and seat belt loading.
      In developing this program, two test dummies were evaluated  for predicting
      occupant injury risk: midsize male Hybrid III and THOR. In the collinear small
      overlap crash tests conducted here,  results from the two dummies were similar.
      Both predicted a low risk of injury to the head and chest and sometimes a high
      risk  of injury to the lower extremities. Head and torso kinematics also were
      similar between dummies. Other test scenarios might  show larger differences
      between the dummies.

PMID- 22869316
TI  - Statistical simulations to evaluate the methods of the construction of injury
      risk curves.
AB  - Several statistical methods are currently used to build injury risk curves in the
      biomechanical field. These methods include the certainty method (Mertz et al.
      1996), Mertz/Weber method (Mertz and Weber 1982), logistic regression (Kuppa et
      al. 2003, Hosmer and Lemeshow 2000), survival analysis with Weibull distribution
      (Kent et al. 2004, Hosmer and Lemeshow 2000), and the consistent threshold
      estimate (CTE) (Nusholtz et al. 1999, Di Domenico and Nusholtz 2005). There is
      currently no consensus on the most accurate method to be used and no guidelines
      to help the user to choose the more appropriate one. Injury risk curves built for
      the WorldSID 50th side impact dummy with these different methods could vary
      significantly, depending on the sample considered (Petitjean et al. 2009). As a
      consequence, further investigations were needed to determine the fields of
      application of the different methods and to recommend the best statistical method
      depending on the biomechanical sample considered. This study used statistical
      simulations on theoretical samples to address these questions. Two different
      theoretical distributions of injury thresholds were utilized to assess the five
      different methods of constructing injury risk curves. A normal distribution and a
      Weibull distribution, whose shape was not similar to a normal distribution, were
      selected. One hundred sets of "test subjects" were randomly chosen from each
      theoretical distribution, with sample sizes ranging from 10 to 50. A "stimulus
      value" was chosen for each "test subject." The stimulus values were equally
      spaced, distributed tightly or loosely about the theoretical mean injury
      threshold, concentrated below the mean value, or concentrated above the mean
      value. An adaptive method was also used to assign stimulus values, based on the
      proportion of uninjured and injured in an early subset of the test subjects. The
      influences of 10%, 25%, and 50% exact data were compared to stimulus values that
      were either right or left censored. The test subject was considered to be
      uninjured if the stimulus was less than the subject's threshold or injured if the
      stimulus was equal to or greater than the subject's threshold. In all, 12,800
      simulated data sets with both normal and Weibull distributions were used to
      construct injury risk curves by each of the five statistical methods. Cumulative
      errors of the constructed injury risk curves, compared to the theoretical curves,
      were calculated across the whole curve, as well as the portion of the theoretical
      curve up to 25% risk of injury. P-values were used to assess the significance of
      the differences in the errors. The CTE and the survival analysis take into
      account the exact data whatever the theoretical distribution of injury threshold,
      while the logistic regression, the Mertz/Weber and the certainty methods do not.
      For left and right censored data, the logistic regression and/or the survival
      analysis lead to the lowest error. The survival analysis leads to the lowest
      error whatever the sample size, the level of censoring and the theoretical
      distribution evaluated. Increasing the sample size generally decreased the error.
      However, the benefit from increasing the sample size decreased when the sample
      size was already high. For the survival analysis, increasing the proportion of
      exact data decreased the error. The same way, the benefit from increasing the
      proportion of exact data decreased when the proportion of exact data was already
      high. Survival analysis may not converge for small sample size with left and
      right censored data. The number of simulations for which the survival analysis
      did not converge highly decreases with the increase of proportion of exact data
      and the increase of the sample size. Therefore, it is recommended to use survival
      analysis with Weibull distribution to build risk curves compared to the four
      other statistical methods evaluated. The accuracy of survival analysis with other
      distributions (log-normal, log-logistic, etc) was not studied. There is no
      recommendation for the method to be used when survival analysis does not
      converge. The balance between maximal acceptable error and the need for an injury
      risk curve, even for a small dataset of poor quality, is not addressed.

PMID- 22869317
TI  - Muscular response to physiologic tensile stretch of the caprine c5/6 facet joint
      capsule: dynamic recruitment thresholds and latencies.
AB  - This study examined the cervical muscle response to physiologic, high-rate (100
      mm/s) tensile facet joint capsule  (FJC) stretch. Six in-vivo caprine C5/6 FJC
      preparations were subjected to an incremental tensile loading paradigm. EMG 
      activity was recorded from the right trapezius (TR) and multifidus (MF) muscle
      groups at the C5 and C6 levels; and from the  sternomastoid (SM) and longus colli
      (LC) muscle groups bilaterally at the C5/6 level; during FJC stretch. Capsule
      load during the  displacement applications was recorded via a miniature load
      cell, and 3D capsule strains (based on stereoimaging of an array of  markers on
      the capsule surface) were reconstructed using finite element methods. EMG traces
      from each muscle were examined  for onset of muscular activity. Capsule strains
      and loads at the time of EMG onset were recorded for each muscle, as was the time
      from the onset of FJC stretch to the onset of muscle activity. All muscles were
      responsive to physiologic high-rate FJC stretch.  The deep muscles (MF and LC)
      were recruited at significantly smaller capsule loads and onset latencies than
      the superficial  muscles (TR and SM). MF activation strain was significantly
      smaller than LC and TR activation strains. These data were also  compared to
      previously published low-rate data. MF was the first muscle group to be recruited
      regardless of the activation  criterion under consideration (i.e. strain, load,
      or latency) or the rate of FJC stretch. LC recruitment occurred significantly
      sooner  under high-rate vs. low-rate FJC stretch. The results of this study
      provide further evidence of extensive ligamento-muscular  reflex pathways between
      the FJC and the cervical musculature, which are responsive to both low-rate and
      high-rate FJC stretch.  These data add to our knowledge of the dynamic response
      of paraspinal muscles relative to facet joint motion and provide a  unique
      contribution to enhance the precision of computer-simulated impacts.

PMID- 22869318
TI  - Performance of collision damage mitigation braking systems and their effects on
      human injury in the event of car-to-pedestrian accidents.
AB  - The number of traffic deaths in Japan was 4,863 in 2010. Pedestrians account for
      the highest number (1,714, 35%), and vehicle occupants the second highest (1,602,
      33%). Pedestrian protection is a key countermeasure to reduce casualties in
      traffic accidents. A striking vehicle's impact velocity could be considered a
      parameter influencing the severity of injury and possibility of death in
      pedestrian crashes. A collision damage mitigation braking system (CDMBS) using a
      sensor to detect pedestrians could be effective for reducing the
      vehicle/pedestrian impact velocity. Currently in Japan, cars equipped with the
      CDMBS also have vision sensors such as a stereo camera for pedestrian detection.
      However, the ability of vision sensors in production cars to properly detect
      pedestrians has not yet been established. The effect of reducing impact velocity
      on the pedestrian injury risk has also not been determined. The first objective
      of this study is to evaluate the performance of the CDMBS in detecting
      pedestrians when it is installed in production cars. The second objective of this
      study is to evaluate the effect of reducing impact velocity on mitigating
      pedestrian injury. Firstly, impact experiments were performed using a car with
      the CDMBS in which the car collided with a pedestrian surrogate. In these tests,
      the velocity was chosen for the various test runs to be 20, 40 and 60 km/h,
      respectively, which were based on the velocity distribution in real-world
      pedestrian crashes. The results indicated that the impact velocity reduction
      ranged approximately from 10 to 15 km/h at the standing location of a pedestrian
      surrogate at both daytime and nighttime lighting conditions. These results show
      that the system has the potential to reduce pedestrian casualties from car-to
      pedestrian contacts. Secondly, finite-element analyses were performed simulating
      vehicle-to- pedestrian impacts with the THUMS pedestrian models. The vehicle
      models selected for the study included a medium sedan, a minicar, and an SUV.
      Since head and chest injuries are the most typical causes of pedestrian deaths in
      car-to-pedestrian accidents, the risk of head and chest injuries was calculated
      when the impact velocity was reduced from 50 km/h to 40 km/h, 30 km/h, and 20
      km/h. The results revealed that an impact velocity reduction of 10 km/h mitigated
      severe pedestrian injury at impact velocities greater than or equal to 40 km/h.
      Specifically, a significant effect was observed in collisions with the medium
      sedan and SUV. In Japan, the CDMBS has just started to be installed in medium
      sedans. The pedestrian injury mitigation will be greatly improved if the system
      can be applied to various types of vehicles including SUVs in the future.

PMID- 22869319
TI  - Patterns of acetabular femoral head coverage.
AB  - The size and shape of the acetabulum and of the femoral head influence the injury
      tolerance of the hip joint. The aim of this study is to quantify changes in
      acetabular cup geometry that occur with age, gender, height, and weight.
      Anonymized computed tomography (CT) scans of 1,150 individuals 16+ years of age,
      both with and without hip trauma, were used to describe the acetabular rim with
      100 equally spaced points. Bilateral measurements were taken on uninjured
      patients, while only the uninjured side was valuated in those with hip trauma.
      Multinomial logistic regression found that after controlling for age, height,
      weight, and gender, each 1 degree decrease in acetabular anteversion angle (AAA)
      corresponded to an 8 percent increase in fracture likelihood (p<0.001). Age,
      weight, and gender were found to influence anteversion angle significantly, with
      each 10 years in age increasing AAA by 1.07 degrees, each 10 kg of weight
      decreasing AAA by 0.45 degrees, and being female resulting in 1.42 degrees
      greater AAA than males. Height was not found to relate significantly to AAA after
      other anthropometric factors were controlled for. Height, age, and weight,
      however, correlated with femoral head radius, thus establishing a relationship
      with acetabular rim size independent of rim shape. A parametric model of the 3D
      acetabular rim landmark points is reported, allowing for the creation of
      individualized acetabular geometry for any given age, gender, height, and weight.
      A custom-built tool to produce such geometry programmatically is also provided.

PMID- 22869321
TI  - Common polymorphism near the MC4R gene is associated with type 2 diabetes: data
      from a meta-analysis of 123,373 individuals.
AB  - AIMS/HYPOTHESIS: Genome-wide association studies have shown that variants near
      the melanocortin 4 receptor gene (MC4R) (rs17782313 and rs12970134) are
      associated with risk of obesity in Europeans. As obesity is associated with an
      increased risk of type 2 diabetes, many studies have investigated the association
      between polymorphisms near the MC4R gene and type 2 diabetes risk across
      different ethnic populations, with inconsistent results. In this study, we
      performed a meta-analysis to clarify the association of variants near MC4R with
      type 2 diabetes risk. METHODS: Published literature from PubMed and Embase was
      retrieved. All studies that evaluated the association of at least one of the two
      MC4R polymorphism(s) with type 2 diabetes were included in the study. Pooled ORs
      with 95% CIs were calculated using the fixed-effects model. RESULTS: A total of
      19 studies (comprising 34,195 cases and 89,178 controls) of the rs17782313
      polymorphism (or its proxy rs12970134) were included in the meta-analysis. The
      results indicated that the rs17782313 polymorphism was significantly associated
      with type 2 diabetes risk among the overall study population (OR 1.10, 95% CI
      1.07, 1.13, p = 2.83 * 10(-12) [Z test], I(2) = 9.1%, p = 0.345 [heterogeneity]).
      The association remained significant even after adjustment for body mass index
      (BMI) (OR 1.06, 95% CI 1.03, 1.09, p = 2.14 * 10(-5) [Z test], I(2) = 4.9%, p =
      0.397 [heterogeneity]). Further sensitivity analysis confirmed the statistically
      significant association of rs17782313 polymorphism with type 2 diabetes, and no
      publication bias was detected. CONCLUSIONS/INTERPRETATION: The present meta
      analysis confirmed the significant association of the rs17782313 polymorphism
      near the MC4R gene with type 2 diabetes risk, which was independent of BMI.

PMID- 22869322
TI  - The ghrelin O-acyltransferase-ghrelin system reduces TNF-alpha-induced apoptosis
      and autophagy in human visceral adipocytes.
AB  - AIMS/HYPOTHESIS: Proinflammatory and proapoptotic cytokines such as TNF-alpha are
      upregulated in human obesity. We evaluated the association between ghrelin
      isoforms (acylated and desacyl ghrelin) and TNF-alpha in obesity and obesity
      associated type 2 diabetes, as well as the potential role of ghrelin in the
      control of apoptosis and autophagy in human adipocytes. METHODS: Plasma
      concentrations of the ghrelin isoforms and TNF-alpha were measured in 194
      participants. Ghrelin and ghrelin O-acyltransferase (GOAT) levels were analysed
      by western-blot, immunohistochemistry and real-time PCR in 53 biopsies of human
      omental adipose tissue. We also determined the effect of acylated and desacyl
      ghrelin (10 to 1,000 pmol/l) on TNF-alpha-induced apoptosis and autophagy-related
      molecules in omental adipocytes. RESULTS: Circulating concentrations of acylated
      ghrelin and TNF-alpha were increased, whereas desacyl ghrelin levels were
      decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced
      in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese
      patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte
      apoptosis and increased expression of the autophagy-related genes ATG5, BECN1 and
      ATG7. In differentiating human omental adipocytes, incubation with acylated and
      desacyl ghrelin reduced TNF-alpha-induced activation of caspase-8 and caspase-3,
      and cell death. In addition, acylated ghrelin reduced the basal expression of the
      autophagy-related genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF
      alpha-induced increase of ATG5, BECN1 and ATG7 expression.
      CONCLUSIONS/INTERPRETATION: Apoptosis and autophagy are upregulated in human
      visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl
      ghrelin reduce TNF-alpha-induced apoptosis and autophagy in human visceral
      adipocytes.

PMID- 22869323
TI  - Endoscopy in the elderly.
AB  - With increasing age, the incidence of both benign and malignant gastrointestinal
      (GI) disease rises. Endoscopic procedures are commonly performed in elderly and
      very elderly patients to diagnose and treat GI disorders. There are a number of
      issues to contemplate when considering performing an endoscopic procedure in an
      elderly patient, including the anticipated benefits of endoscopy as well as the
      increased risks associated with procedural sedation and some endoscopic
      procedures. This review will focus on the yield and safety of endoscopic
      procedures in older adults.

PMID- 22869325
TI  - Urban Latino children's physical activity levels and performance in interactive
      dance video games: effects of goal difficulty and goal specificity.
AB  - OBJECTIVE: To examine the effects of different levels of goal specificity and
      difficulty on Latino children's performance and physical activity (PA) levels in
      an after-school program incorporating an interactive dance program (Dance Dance
      Revolution [DDR]; Konami Corporation). DESIGN: Comparison study. SETTING: Rose
      Park Elementary School, Salt Lake City, Utah. PARTICIPANTS: Ninety-eight Latino
      children in the first through sixth grades, aged 7 to 13 years. INTERVENTION:
      After the pretest, the participants were randomly assigned into 1 of the
      following 3 goal-setting conditions: (1) easy, (2) difficult, and (3) best effort
      (hereinafter referred to as do-your-best goal). MAIN OUTCOME MEASURES:
      Participants' PA levels were measured using piezoelectric pedometers, and steps
      per minute were used as the outcome variable. Participants' total points for
      their dance on television screens were retrieved as their performance scores.
      These outcome variables were assessed again 8 weeks later (posttest score).
      RESULTS: The multivariate analysis of covariance yielded a significant main
      effect for the goal-setting condition. Follow-up tests revealed that children who
      set specific (easy or difficult) goals had significantly greater increased PA
      levels (mean scores, 10.34 for easy and 22.45 for difficult) and DDR performance
      (0.011 for easy and 0.67 for difficult) than those in the do-your-best group
      (0.83 for PA and 0.17 for performance). In addition, children's increased PA
      levels in the difficult-goal group were significantly higher than those in the
      easy-goal group. CONCLUSIONS: The easy- and difficult-goal groups show a
      significant improvement on DDR performance. The difficult- goal group also
      displays the highest improvement on PA levels. Strategies to enhance children's
      DDR performance and PA levels are discussed in relation to the extant goal
      setting literature.

PMID- 22869326
TI  - Stroke increases g protein-coupled estrogen receptor expression in the brain of
      male but not female mice.
AB  - The novel estrogen receptor, G protein-coupled estrogen receptor (GPER,
      previously named GPR30), is widely distributed throughout the male and female
      brain and, thus, could potentially play a role in estrogen-mediated
      neuroprotective effects in diseases such as stroke. We hypothesized that GPER
      distribution and expression in the brain of male, intact female, and
      ovariectomized (OVX) mice is increased after 0.5 h middle cerebral artery
      occlusion. Using immunohistochemistry, we found that ischemia reperfusion
      increased GPER distribution in the peri-infarct brain regions of male mice, but
      surprisingly not in intact females or OVX mice. Similar differences were observed
      in the male and female human brain after stroke. In contrast, GPER distribution
      was decreased in the infarct core of all mice examined. Furthermore, GPER
      immunofluorescence was co-localized with the endothelial cell marker, von
      Willebrand factor, and the neuronal marker, NeuN. Consistent with the
      immunohistochemical findings, Western blot analysis showed GPER expression is
      only elevated in the ischemic hemisphere of male mice. Moreover, GPER mRNA
      expression in males was elevated at 4 h but had returned to baseline by 24 h. In
      conclusion, these findings indicate that GPER may be a potential therapeutic
      target after stroke, especially in males, in whom estrogen therapy is not
      feasible.

PMID- 22869324
TI  - Parent and family impact of autism spectrum disorders: a review and proposed
      model for intervention evaluation.
AB  - Raising a child with an autism spectrum disorder (ASD) can be an overwhelming
      experience for parents and families. The pervasive and severe deficits often
      present in children with ASD are associated with a plethora of difficulties in
      caregivers, including decreased parenting efficacy, increased parenting stress,
      and an increase in mental and physical health problems compared with parents of
      both typically developing children and children with other developmental
      disorders. In addition to significant financial strain and time pressures, high
      rates of divorce and lower overall family well-being highlight the burden that
      having a child with an ASD can place on families. These parent and family effects
      reciprocally and negatively impact the diagnosed child and can even serve to
      diminish the positive effects of intervention. However, most interventions for
      ASD are evaluated only in terms of child outcomes, ignoring parent and family
      factors that may have an influence on both the immediate and long-term effects of
      therapy. It cannot be assumed that even significant improvements in the diagnosed
      child will ameliorate the parent and family distress already present, especially
      as the time and expense of intervention can add further family disruption. Thus,
      a new model of intervention evaluation is proposed, which incorporates these
      factors and better captures the transactional nature of these relationships.

PMID- 22869327
TI  - Targeted therapies: STAT3 and EGFR target resistance.

PMID- 22869320
TI  - Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin
      receptor substrate proteins IRS1 and IRS2.
AB  - The insulin receptor substrate proteins IRS1 and IRS2 are key targets of the
      insulin receptor tyrosine kinase and are required for hormonal control of
      metabolism. Tissues from insulin-resistant and diabetic humans exhibit defects in
      IRS-dependent signalling, implicating their dysregulation in the initiation and
      progression of metabolic disease. However, IRS1 and IRS2 are regulated through a
      complex mechanism involving phosphorylation of >50 serine/threonine residues
      (S/T) within their long, unstructured tail regions. In cultured cells, insulin
      stimulated kinases (including atypical PKC, AKT, SIK2, mTOR, S6K1, ERK1/2 and
      ROCK1) mediate feedback (autologous) S/T phosphorylation of IRS, with both
      positive and negative effects on insulin sensitivity. Additionally, insulin
      independent (heterologous) kinases can phosphorylate IRS1/2 under basal
      conditions (AMPK, GSK3) or in response to sympathetic activation and
      lipid/inflammatory mediators, which are present at elevated levels in metabolic
      disease (GRK2, novel and conventional PKCs, JNK, IKKbeta, mPLK). An emerging view
      is that the positive/negative regulation of IRS by autologous pathways is
      subverted/co-opted in disease by increased basal and other temporally
      inappropriate S/T phosphorylation. Compensatory hyperinsulinaemia may contribute
      strongly to this dysregulation. Here, we examine the links between altered
      patterns of IRS S/T phosphorylation and the emergence of insulin resistance and
      diabetes.

PMID- 22869328
TI  - Immunotherapy: Harmonizing the immune response with a cancer vaccine.

PMID- 22869329
TI  - Health policy: Upholding the Affordable Care Act--implications for oncology.

PMID- 22869330
TI  - MET targeting: perspectives for the radiation oncologist.

PMID- 22869331
TI  - Breast cancer: Fewer therapy cycles is better.

PMID- 22869332
TI  - Genetics: Identifying driver mutations with the help of viruses.

PMID- 22869333
TI  - Sun protection for all: but especially for those receiving certain hypertensive
      medications: comment on "Antihypertensive drugs and lip cancer in non-Hispanic
      whites".

PMID- 22869334
TI  - Nonprobative photographs (or words) inflate truthiness.
AB  - When people evaluate claims, they often rely on what comedian Stephen Colbert
      calls "truthiness," or subjective feelings of truth. In four experiments, we
      examined the impact of nonprobative information on truthiness. In Experiments 1A
      and 1B, people saw familiar and unfamiliar celebrity names and, for each, quickly
      responded "true" or "false" to the (between-subjects) claim "This famous person
      is alive" or "This famous person is dead." Within subjects, some of the names
      appeared with a photo of the celebrity engaged in his or her profession, whereas
      other names appeared alone. For unfamiliar celebrity names, photos increased the
      likelihood that the subjects would judge the claim to be true. Moreover, the same
      photos inflated the subjective truth of both the "alive" and "dead" claims,
      suggesting that photos did not produce an "alive bias" but rather a "truth bias."
      Experiment 2 showed that photos and verbal information similarly inflated
      truthiness, suggesting that the effect is not peculiar to photographs per se.
      Experiment 3 demonstrated that nonprobative photos can also enhance the
      truthiness of general knowledge claims (e.g., Giraffes are the only mammals that
      cannot jump). These effects add to a growing literature on how nonprobative
      information can inflate subjective feelings of truth.

PMID- 22869336
TI  - Evaluating a group-based intervention to improve the safety of meat in Bodija
      market, Ibadan, Nigeria.
AB  - We evaluated a group-based, participatory training intervention to improve food
      safety among meat processors and retailers in Bodija Market, Ibadan, Nigeria. An
      interactive training workshop was held for Butchers Associations' representatives
      who were selected to pass on information and training to their group. Meat
      hygiene knowledge, attitude and practice was assessed before attending the
      workshop and afterwards (n = 63). It was also assessed for those who did not
      attend the workshop (n = 68) but were intended recipients of training through
      their association. Microbiological quality of meat was assessed before and after
      the workshop (n = 400 samples). After the workshop, participants significantly
      improved knowledge, attitude and practice in key food safety aspects;
      specifically, understanding sources of contamination and food-borne diseases, use
      of bleach and disinfectant and hand washing. Participants also shared information
      with an average of 18 other group members and improvements were seen in group
      members who did not attend the workshop but received training through their
      Butchers Association. Microbiological quality of meat sold also significantly
      improved after the intervention. In conclusion, participatory, group-based
      methods targeted at meat processors and retailers can improve meat hygiene
      knowledge, attitude and practice as well as the microbiological quality and hence
      safety of meat.

PMID- 22869335
TI  - Using priors to formalize theory: optimal attention and the generalized context
      model.
AB  - Formal models in psychology are used to make theoretical ideas precise and allow
      them to be evaluated quantitatively against data. We focus on one important--but
      under-used and incorrectly maligned--method for building theoretical assumptions
      into formal models, offered by the Bayesian statistical approach. This method
      involves capturing theoretical assumptions about the psychological variables in
      models by placing informative prior distributions on the parameters representing
      those variables. We demonstrate this approach of casting basic theoretical
      assumptions in an informative prior by considering a case study that involves the
      generalized context model (GCM) of category learning. We capture existing
      theorizing about the optimal allocation of attention in an informative prior
      distribution to yield a model that is higher in psychological content and lower
      in complexity than the standard implementation. We also highlight that
      formalizing psychological theory within an informative prior distribution allows
      standard Bayesian model selection methods to be applied without concerns about
      the sensitivity of results to the prior. We then use Bayesian model selection to
      test the theoretical assumptions about optimal allocation formalized in the
      prior. We argue that the general approach of using psychological theory to guide
      the specification of informative prior distributions is widely applicable and
      should be routinely used in psychological modeling.

PMID- 22869337
TI  - Local poultry biosecurity risks to highly pathogenic avian influenza in Kaduna
      State, Nigeria.
AB  - The study appraised local poultry biosecurity risks to highly pathogenic avian
      influenza by assessing farmers' knowledge, beliefs and poultry practices using a
      standard questionnaire. Farmers' knowledge on transmission and prevention was
      high but low on disease recognition. Radio was ineffective at informing Islamic
      educated farmers. Extensive knowledge on transmission and protection did not
      result in behavioural change as farmers engaged in risky practices of selling,
      eating or medicating infected poultry and not reporting poultry death. Islamic
      educated farmers do not believe highly pathogenic avian influenza is a serious
      and preventable disease. Women are more likely to self medicate when experiencing
      influenza-like illness. Audio-visual aids would improve avian influenza
      recognition while involvement of community leaders would enhance disease
      reporting. Outbreak of highly pathogenic avian influenza in local poultry in
      Nigeria would follow a similar pattern in Southeast Asia if the risk perception
      among farmers is not urgently articulated.

PMID- 22869338
TI  - Rectal temperature responses of donkeys administered with ascorbic acid and
      subjected to load carrying (packing) during the harmattan season in Nigeria.
AB  - The aim of the experiment was to evaluate the effect of 4-h load carrying
      (packing) on donkeys administered with ascorbic acid (AA) during the harmattan
      season. Six donkeys administered orally with ascorbic acid (200 mg/kg) and
      subjected to packing served as experimental animals, while six others given only
      distilled water served as control animals. The rectal temperature (RT) of each
      donkey and dry-bulb temperature (DBT) and relative humidity (RH) of the research
      pen were recorded at 0600 hours pre-packing; while post-packing, the values were
      obtained at 1430, 1600 and 1800 hours. The DBT values (ranges) recorded before,
      during and after packing were 13.7 +/- 1.3  degrees C (11-15  degrees C), 28.4 +/
      1.0  degrees C (22.7-30.3  degrees C) and 30.6 +/- 3.0  degrees C (19.8-45 
      degrees C), respectively. The highest temperature-humidity index (THI) of 83.4 +/
      6.9 was obtained at 1430 hours after packing, and the value decreased to 64.2 +/
      5.8 at 1800 hours. The thermal environmental conditions were outside the
      thermoneutral zone for the donkeys. The RT values recorded immediately after
      packing did not differ (P > 0.05) in experimental and control donkeys; but at
      1600 and 1800 hours, values obtained in control donkeys (38.48 +/- 0.12 and 38.12
      +/- 0.12  degrees C, respectively) were significantly higher (P < 0.05) than
      those recorded in experimental donkeys (38.16 +/- 0.14 and 37.85 +/- 0.14 
      degrees C, respectively). In conclusion, administration of ascorbic acid reduced
      the rise in RT due to packing and may be of value in the amelioration of adverse
      effects of heat stress associated with work in donkeys.

PMID- 22869339
TI  - Prevalence and risk factors associated with Neospora caninum infection in dairy
      herds in Jordan.
AB  - A cross-sectional study was carried out to determine the seroprevalence and to
      identify risk factors associated with Neospora caninum infection in 62 dairy
      herds (n = 671 cows) in Jordan between January and June 2007. Information
      regarding herd management was recorded through personal interviews with farmers.
      Antibodies against N. caninum were detected using an indirect ELISA test. Chi
      square analysis and multivariable logistic regression model were used to identify
      risk factors associated with N. caninum seropositivity. The true prevalence of
      antibodies against N. caninum in individual cows and cattle herds was 35 and 66.5
      %, respectively. There was no significant difference in the percentage of
      seropositive animals between different age groups. Multivariable logistic
      regression model revealed workers frequently visiting nearby farms as a risk
      factor for seropositivity to N. caninum, while presence of a calving pen was
      suggested as a protective factor. Amman, Balqa, and Mafrak governorates had
      significantly lower seroprevalence to N. caninum compared to other Jordanian
      governorates. Results of this study indicated that N. caninum infection may be
      widespread in Jordan.

PMID- 22869341
TI  - Similar predictions of etravirine sensitivity regardless of genotypic testing
      method used: comparison of available scoring systems.
AB  - BACKGROUND: The aims of this study were to compare various genotypic scoring
      systems commonly used to predict virological outcome to etravirine, and examine
      their concordance with etravirine phenotypic susceptibility. METHODS: Six
      etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20
      mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and
      49 mutations, respectively) and virco((r))TYPE HIV-1 (predicted fold change based
      on genotype). Samples from treatment-experienced patients who participated in the
      DUET trials and with both genotypic and phenotypic data (n=403) were assessed
      using each scoring system. Results were retrospectively correlated with
      virological response in DUET. kappa coefficients were calculated to estimate the
      degree of correlation between the different scoring systems. RESULTS: Correlation
      between the five scoring systems and the TBT 20 system was approximately 90%.
      Virological response by etravirine susceptibility was comparable regardless of
      which scoring system was utilized, with 70-74% of DUET patients determined as
      susceptible to etravirine by the different scoring systems achieving plasma viral
      load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to
      etravirine (fold change in 50% effective concentration <=3), correlations with
      genotypic score were consistently high across scoring systems (>=70%).
      CONCLUSIONS: In general, the etravirine genotypic scoring systems produced
      similar results, and genotype-phenotype concordance was high. As such, phenotypic
      interpretations, and in their absence all genotypic scoring systems investigated,
      may be used to reliably predict the activity of etravirine.

PMID- 22869340
TI  - Transcription initiation factor IIB involves in Schwann cell differentiation
      after rat sciatic nerve crush.
AB  - Transcription Initiation Factor IIB (TFIIB), as a general transcription factor,
      plays an essential role in preinitiation complex assembly and transcription
      initiation by recruiting RNA polymerase II to the promoter. However, its
      distribution and function in peripheral system lesion and repair were still
      unknown. Here, we investigated the spatiotemporal expression of TFIIB in an acute
      sciatic nerve crush model in adult rats. Western blot analysis revealed that
      TFIIB was expressed in normal sciatic nerve. It gradually increased, reached a
      peak at the seventh day after crush, and then returned to the normal level at 4
      weeks. We observed that TFIIB expressed mainly increased in Schwann cells and co
      localized with Oct-6. In vitro, we induced Schwann cell differentiation with
      cyclic adenosine monophosphate (cAMP) and found that TFIIB expression was
      increased in the differentiated process. TFIIB-specific siRNA inhibited cAMP
      induced Schwann cell morphological change and the expression of P0. Collectively,
      we hypothesized peripheral nerve crush-induced upregulation of TFIIB in the
      sciatic nerve was associated with Schwann cell differentiation.

PMID- 22869342
TI  - Interstitial fluid flow within bone canaliculi and electro-chemo-mechanical
      features of the canalicular milieu: a multi-parametric sensitivity analysis.
AB  - Canalicular fluid flow is acknowledged to play a major role in bone functioning,
      allowing bone cells' metabolism and activity and providing an efficient way for
      cell-to-cell communication. Bone canaliculi are small canals running through the
      bone solid matrix, hosting osteocyte's dendrites, and saturated by an
      interstitial fluid rich in ions. Because of the small size of these canals (few
      hundred nanometers in diameter), fluid flow is coupled with electrochemical
      phenomena. In our previous works, we developed a multi-scale model accounting for
      coupled hydraulic and chemical transport in the canalicular network.
      Unfortunately, most of the physical and geometrical information required by the
      model is hardly accessible by nowadays experimental techniques. The goal of this
      study was to numerically assess the influence of the physical and material
      parameters involved in the canalicular fluid flow. The focus was set on the
      electro-chemo-mechanical features of the canalicular milieu, hopefully covering
      any in vivo scenario. Two main results were obtained. First, the most relevant
      parameters affecting the canalicular fluid flow were identified and their effects
      quantified. Second, these findings were given a larger scope to cover also
      scenarios not considered in this study. Therefore, this study gives insight into
      the potential interactions between electrochemistry and mechanics in bone and
      provides the rational for further theoretical and experimental investigations.

PMID- 22869343
TI  - Computational simulation of hemodynamic-driven growth and remodeling of embryonic
      atrioventricular valves.
AB  - Embryonic heart valves develop under continuous and demanding hemodynamic
      loading. The particular contributions of fluid pressure and shear tractions in
      valve morphogenesis are difficult to decouple experimentally. To better
      understand how fluid loads could direct valve formation, we developed a
      computational model of avian embryonic atrioventricular (AV) valve (cushion)
      growth and remodeling using experimentally derived parameters for the blood flow
      and the cushion stiffness. Through an iterative scheme, we first solved the fluid
      loads on the axisymmetric AV canal and cushion model geometry. We then applied
      the fluid loads to the cushion and integrated the evolution equations to
      determine the growth and remodeling. After a set time of growth, we updated the
      fluid domain to reflect the change in cushion geometry and resolved for the fluid
      forces. The rate of growth and remodeling was assumed to be a function of the
      difference between the current stress and an isotropic homeostatic stress state.
      The magnitude of the homeostatic stress modulated the rate of volume addition
      during the evolution. We found that the pressure distribution on the AV cushion
      was sufficient to generate leaflet-like elongation in the direction of flow,
      through inducing tissue resorption on the inflow side of cushion and expansion on
      the outflow side. Conversely, shear tractions minimally altered tissue volume,
      but regulated the remodeling of tissue near the cushion surface, particular at
      the leading edge. Significant shear and circumferential residual stresses
      developed as the cushion evolved. This model offers insight into how natural and
      perturbed mechanical environments may direct AV valvulogenesis and provides an
      initial framework on which to incorporate more mechano-biological details.

PMID- 22869344
TI  - Gogo care and protection of vulnerable children in rural Malawi: changing
      responsibilities, capacity to provide, and implications for well-being in the era
      of HIV and AIDS.
AB  - The role of older women in the care and protection of vulnerable children in sub
      Saharan Africa may be changing given increasing rates of orphanhood due to AIDS.
      Concern regarding their capacity to provide for children and implications for
      their health and well-being dominate the literature. However, studies have not
      yet examined the situation of older caregivers in comparison to their younger
      counterparts over time. In this study, panel data on 1,219 caregivers in rural
      Malawi between 2007 and 2009 is complemented by in-depth interview (N=62) and
      group discussion (N=4) data. Caregiver responsibilities, capacity to care for
      children, and implications for well-being are examined. Chi-square tests examine
      differences in these measures between older foster caregivers and younger foster
      caregivers, parents of orphans, and parents of non-orphans. Older women, in
      comparison with younger counterparts, are more stable as primary caregivers for
      orphans. Care by older women is particularly valued when younger family stability
      is threatened by burdens of orphan care. Qualitative data reveal many challenges
      that older caregivers face, most notably provision of food. However, survey data
      suggest that the capacity to provide food, schooling and other basic needs is
      similar among older and younger caregivers. Self-reported health status is
      generally poorer among older caregivers, however levels of emotional distress and
      social capital are similar among older and younger caregivers. Providing care for
      children in old age appears to entail a number of benefits. Older women committed
      to providing care and protection for children are important assets, particularly
      in the context of threats to child well-being due to HIV and AIDS. Bolstering
      older caregivers with material and social support to help sustain their key roles
      in fostering is a promising avenue for maintaining extended family responses to
      HIV and AIDS.

PMID- 22869345
TI  - Individualism, collectivism and ethnic identity: cultural assumptions in
      accounting for caregiving behaviour in Britain.
AB  - Britain is experiencing the ageing of a large number of minority ethnic groups
      for the first time in its history, due to the post-war migration of people from
      the Caribbean and the Indian subcontinent. Stereotypes about a high level of
      provision of informal caregiving among minority ethnic groups are common in
      Britain, as in the US, despite quantitative studies refuting this assumption.
      This paper reports on a qualitative analysis of in-depth interviews with older
      people from five different ethnic groups about their conceptualisation of their
      ethnic identity, and their attributions of motivations of caregiving within their
      own ethnic group and in other groups. It is argued that ethnic identity becomes
      salient after migration and becoming a part of an ethnic minority group in the
      new country. Therefore, White British people who have never migrated do not have
      a great sense of ethnic identity. Further, a strong sense of ethnic identity is
      linked with identifying with the collective rather than the individual, which
      explains why the White British participants gave an individualist account of
      their motivations for informal care, whereas the minority ethnic participants
      gave a collectivist account of their motivations of care. Crucially, members of
      all ethnic groups were providing or receiving informal care, so it was the
      attribution and not the behaviour which differed.

PMID- 22869347
TI  - Evidence for a celiac ganglion-ovarian kisspeptin neural network in the rat:
      intraovarian anti-kisspeptin delays vaginal opening and alters estrous cyclicity.
AB  - Kisspeptin and its receptor GPR54 have been described as key hypothalamic
      components in the regulation of GnRH secretion. Kisspeptin is also present in
      several regions of the central nervous system and the peripheral organs and has
      recently been identified in the superior ganglion. Herein, we tested the
      possibility that ovarian kisspeptin is regulated by the sympathetic nervous
      system and participates locally in the regulation of ovarian function. Both
      ovarian and celiac ganglion kisspeptin mRNA levels increase during development,
      whereas kisspeptin peptide levels and plasma levels decrease during development.
      In the celiac ganglion, kisspeptin colocalized with tyrosine hydroxylase,
      indicating potential kisspeptin synthesis and transport within the sympathetic
      neurons. A continuous (64 h) cold stress induced marked changes within the
      kisspeptin neural system along the celiac ganglion-ovary axis. In vitro
      incubation with the beta-adrenergic agonist isoproterenol increased ovarian
      kisspeptin mRNA and peptide levels, and this increase was inhibited by treatment
      with the beta-antagonist propranolol. Sectioning the superior ovarian nerve
      altered the feedback information within the kisspeptin celiac ganglion-ovary
      axis. In vivo administration of a kisspeptin antagonist to the left ovarian bursa
      of 22- to 50-d-old unilaterally ovariectomized rats delayed the vaginal opening,
      decreased the percentage of estrous cyclicity, and decreased plasma, ovarian, and
      celiac ganglion kisspeptin concentrations but did not modify the LH plasma
      levels. These results indicate that the intraovarian kisspeptin system may be
      regulated by sympathetic nerve activity and that the peptide, either from a
      neural or ovarian origin, is required for proper coordinated ovarian function.

PMID- 22869346
TI  - Neurochemical characterization of body weight-regulating leptin receptor neurons
      in the nucleus of the solitary tract.
AB  - The action of peripherally released leptin at long-form leptin receptors (LepRb)
      within the brain represents a fundamental axis in the regulation of energy
      homeostasis and body weight. Efforts to delineate the neuronal mediators of
      leptin action have recently focused on extrahypothalamic populations and have
      revealed that leptin action within the nucleus of the solitary tract (NTS) is
      critical for normal appetite and body weight regulation. To elucidate the
      neuronal circuits that mediate leptin action within the NTS, we employed multiple
      transgenic reporter lines to characterize the neurochemical identity of LepRb
      expressing NTS neurons. LepRb expression was not detected in energy balance
      associated NTS neurons that express cocaine- and amphetamine-regulated
      transcript, brain-derived neurotrophic factor, neuropeptide Y, nesfatin,
      catecholamines, gamma-aminobutyric acid, prolactin-releasing peptide, or nitric
      oxide synthase. The population of LepRb-expressing NTS neurons was comprised of
      subpopulations marked by a proopiomelanocortin-enhanced green fluorescent protein
      (EGFP) transgene and distinct populations that express proglucagon and/or
      cholecystokinin. The significance of leptin action on these three populations of
      NTS neurons was assessed in leptin-deficient Ob/Ob mice, revealing increased NTS
      proglucagon and cholecystokinin, but not proopiomelanocortin, expression. These
      data provide new insight into the appetitive brainstem circuits engaged by
      leptin.

PMID- 22869348
TI  - Endogenous glucocorticoids in inflammation: contributions of systemic and local
      responses.
AB  - The anti-inflammatory actions of therapeutic glucocorticoids are well established
      and these drugs are widely used to treat a variety of inflammatory conditions. It
      is also clear that endogenously synthesised glucocorticoids have an important
      role in regulating inflammatory responses. Traditionally, our understanding of
      the effects of endogenous glucocorticoids has been based on the levels of
      glucocorticoids within the circulation. These levels are controlled by the
      hypothalamic-pituitary-adrenal axis. However, more recently it has been
      established that the local level of glucocorticoids is of potential importance.
      Situations where the local level of glucocorticoids may differ from the level in
      the circulation are illustrated in this review. In addition, the mechanisms
      regulating local glucocorticoid levels and actions are identified. Increasingly,
      it will be important to understand how the levels of glucocorticoids within the
      circulation and within the tissues are regulated in a coordinated manner.

PMID- 22869349
TI  - Relationship between adverse childhood experiences and unemployment among adults
      from five U.S. states.
AB  - PURPOSE: Our study assesses the relationships between self-reported adverse
      childhood experiences (ACEs) (including sexual, physical, or verbal abuse, along
      with household dysfunction including parental separation or divorce, domestic
      violence, mental illness, substance abuse, or incarcerated household member) and
      unemployment status in five US states in 2009. METHODS: We examined these
      relationships using the 2009 Behavioral Risk Factor surveillance system survey
      data from 17,469 respondents (aged 18-64 years) who resided in five states,
      completed the ACE Questionnaire, and provided socio-demographic and social
      support information. We also assessed the mediation of these relationships by
      respondents' educational attainment, marital status, and social support. RESULTS:
      About two-third of respondents reported having had at least one ACEs, while 15.1%
      of men and 19.3% of women reported having had >=4 ACEs. Among both men and women,
      the unemployment rate in 2009 was significantly higher among those who reported
      having had any ACE than among those who reported no ACEs (p < 0.05). Educational
      attainment, marital status, and social support mediated the relationship between
      ACEs and unemployment, particularly among women. CONCLUSIONS: ACEs appear to be
      associated with increased risk for unemployment among men and women. Further
      studies may be needed to better understand how education, marital status, and
      social support mediate the association between multiple ACEs and unemployment.

PMID- 22869350
TI  - Hydroalcoholic extract of cyperus rotundus ameliorates H2O2-induced human
      neuronal cell damage via its anti-oxidative and anti-apoptotic machinery.
AB  - Hydrogen peroxide (H(2)O(2)), a major reactive oxygen species produced during
      oxidative stress, has been implicated in the pathophysiology of various
      neurodegenerative conditions. Cyperus rotundus is a traditional medicinal herb
      that has recently found applications in food and confectionary industries. In the
      current study, the neuroprotective effects of Cyperus rotundus rhizome extract
      (CRE) through its antioxidant and anti-apoptotic machinery to attenuate H(2)O(2)
      induced cell damage on human neuroblastoma SH-SY5Y cells have been explored. The
      results obtained demonstrate that pretreatment of cells with CRE for 2 h before
      administration of H(2)O(2) for 24 h ameliorates the cytotoxicity induced by
      H(2)O(2) as evidenced by MTT and LDH assays. CRE exhibited potent antioxidant
      activity by regulating the enzymes/proteins levels such as SOD, CAT, GPx, GR, HSP
      70, Caspase-3, and Bcl-2. The pretreatment restored H(2)O(2)-induced cellular,
      nuclear, and mitochondrial morphologies as well as increased the expression of
      Brain derived nerve growth factor (BDNF). The anti-oxidant and anti-apoptotic
      potentials of the plant extract may account for its high content of phenolics,
      flavonoids, and other active principles. Taken together, our findings suggest
      that CRE might be developed as an agent for neurodegeneration prevention or
      therapy.

PMID- 22869351
TI  - Does stress-induced release of interleukin-1 cause liver injury?
AB  - It is well established that repeated immobilization stress (RIS) is induced by
      increased levels of cytokines and the emergence of lesions in the liver. Our data
      prove that interleukin-1 (IL-1) causes liver lesions in stressed Wistar rats. In
      essence, the relationship between IL-1 and stress-induced liver injury is based
      on three findings: (1) IL-1beta treatment causes liver inflammation, consisting
      of infiltrating monocytes and the appearance of necrosis by increasing lipid
      peroxidation and protein carbonylation. Positive correlations between the content
      of heptane-soluble diene conjugates and an area of necrosis, as well as between
      content carbonylated proteins and an area of necrosis, were found after injection
      of IL-1beta to unstressed rats. (2) RIS is accompanied by increased levels of
      circulating IL-1beta and corticosterone. In the liver, stress causes the
      emergence of foci of necrosis with perivascular and lobular infiltration of
      mononuclear cells as well as increased free radical oxidation. Moreover, there
      were observed down-regulations of cytochrome P450 (CYP)-dependent enzymes, CYP1A1
      activities, and decreased CYP1A1 mRNA content. Positive correlations between the
      level of circulating IL-1beta and necrosis areas, as well as between circulating
      IL-1beta and the content of heptane-soluble diene conjugates, were observed in
      stressed rats. In addition, the positive correlation between necrosis foci and
      heptane-soluble diene conjugates was revealed after stress cessation. (3) Use of
      the IL-1 receptor antagonist Anakinra at a dose of 2 MUg/kg to treat the effects
      of stress prevents infiltration of mononuclear cells and reduces the level of
      free radical oxidation as well as necrosis of lesions. As a result, blocking IL-1
      receptors with an antagonist significantly rescues stress-induced liver injury,
      suggesting that IL-1 might be involve in the cascade of liver injury that
      initiated by sustained stress.

PMID- 22869352
TI  - An evaluation of the antinociceptive effects of Phalpha1beta, a neurotoxin from
      the spider Phoneutria nigriventer, and omega-conotoxin MVIIA, a cone snail Conus
      magus toxin, in rat model of inflammatory and neuropathic pain.
AB  - Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are
      involved in the mechanisms that generate and maintain neuropathic and
      inflammatory pain. We evaluated in rats the effects of two VSCC blockers, omega
      conotoxin MVIIA and Phalpha1beta, in models of inflammatory and neuropathic pain
      induced with complete Freund's adjuvant (CFA) and chronic constrictive injury
      (CCI), respectively. We also evaluated the effects of the toxins on capsaicin
      induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats
      exposed to both models of pain. A single intrathecal injection of Phalpha1beta
      reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a
      single injection of omega-conotoxin MVIIA. Phalpha1beta and MVIIA also inhibited
      capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of
      Phalpha1beta on capsaicin-induced calcium transients in DRG neurons was greater
      in the CFA model of pain, while the inhibitory effect of omega-conotoxin MVIIA
      was greater in the CCI model. The management of chronic inflammatory and
      neuropathic pain is still a major challenge for clinicians. Phalpha1beta, a
      reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has
      potential as a novel therapeutic agent for inflammatory and neuropathic pain.
      Clinical studies are necessary to establish the role of Phalpha1beta in the
      treatment of chronic pain.

PMID- 22869353
TI  - Simvastatin inhibited the apoptosis of PC12 cells induced by 1-methyl-4
      phenylpyridinium ion via inhibiting reactive oxygen species production.
AB  - In the present study, we investigated the neuroprotection of simvastatin in PC12
      cells following 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity. Simvastatin
      inhibited the decrease of cell viability induced by MPP+ in PC12 cells. The
      damage of PC12 cells in morphology was alleviated and the apoptotic rates were
      decreased due to simvatatin pretreatment against MPP+ cytotoxicity. The reactive
      oxygen species production exposure to MPP+ was inhibited by simvatatin in PC12
      cells. So simvastatin may be of therapeutic benefit for PD patients.

PMID- 22869354
TI  - Television viewing and externalizing problems in preschool children: the
      Generation R Study.
AB  - OBJECTIVE: To determine whether the amount, type, and patterns of television
      viewing predict the onset or the persistence of externalizing problems in
      preschool children. DESIGN: Longitudinal study of a prospective population-based
      cohort in the Netherlands. SETTING: Parents reported time of television exposure
      and type of programs watched by children. Externalizing problems were assessed
      using the Child Behavior Checklist at 18 and 36 months. PARTICIPANTS: A
      population-based sample of 3913 children. MAIN EXPOSURE: Television viewing time,
      content, and patterns of exposure (at 24 and 36 months) in children with and
      without preexisting problems to assess the incidence and persistence of
      externalizing problems. MAIN OUTCOME MEASURES: Externalizing problems at 36
      months. RESULTS: Program content and time of television exposure assessed at 24
      months did not predict the incidence of externalizing problems at 36 months (odds
      ratio, 2.24; 95% CI, 0.97-5.18). However, the patterns of exposure over time
      reflecting high levels of television viewing were associated with the incidence
      of externalizing problems (odds ratio, 2.00; 95% CI, 1.07-3.75) and the
      persistence of the preexisting externalizing problems (2.59; 1.03-6.55).
      CONCLUSIONS: Our study showed that high television exposure increases the risk of
      the incidence and the persistence of externalizing problems in preschool
      children.

PMID- 22869355
TI  - Memory bias for emotional and illness-related words in patients with depression,
      anxiety and somatization disorders: an investigation with the directed forgetting
      task.
AB  - OBJECTIVE: Memory bias to emotion- and illness-related information plays a
      prominent role in many mental disorders, particularly major depressive disorder,
      anxiety disorders and somatoform disorder. The current study aimed to investigate
      memory bias in different mental disorders by using neutral, emotionally valenced
      and illness-related word stimuli in a directed forgetting task. METHODS: Seventy
      eight inpatients from a university-based psychosomatic hospital participated in
      the study. The item method of the directed forgetting task was used, in which
      participants are instructed to either forget or remember each item immediately
      after it has been presented. Memory performance was tested with a free recall
      test. Overall, 36 words were presented - 6 from each of 6 categories: neutral,
      negative, positive, illness related ('somatoform'), depression related, and
      anxiety related. Three words of each category were to be remembered and 3 were to
      be forgotten. RESULTS: Independently of the patients' diagnoses, we found that
      most patients had relative difficulties remembering anxiety- and depression
      related words, compared to neutral words, when they were instructed to remember
      them. By contrast, in the 'instructed forgetting' condition, patients showed
      deficits in the ability to forget illness-related stimuli relative to neutral
      material. These effects were unspecific with regard to diagnosis. CONCLUSIONS:
      The results in the 'instructed remembering' condition might be interpreted in the
      context of cognitive avoidance instead of a memory bias. In the 'instructed
      forgetting' condition, it appeared that illness-related words were more difficult
      to suppress compared to the other word types, which could explain the observed
      memory bias.

PMID- 22869356
TI  - Adenomatoid odontogenic tumor: retrospective study of 15 cases with emphasis on
      histopathologic features.
AB  - Adenomatoid odontogenic tumor (AOT) is an uncommon benign epithelial lesion of
      odontogenic origin and, thus far, only few studies regarding the frequency of its
      many histopathologic features have been published in the literature. Thus, the
      aim of this study was to perform a retrospective analysis in a case series of
      AOT, with emphasis on the histopathological features. Fifteen cases of AOT were
      studied considering their clinical, radiographic and histopathologic aspects.
      Twelve cases affected females and the mean age was 16.2 years. The anterior
      maxilla was the most common site (66.6 %) and radiographically most cases showed
      a unilocular radiolucency with well-defined borders (57.1 %). Histologically,
      most cases exhibited predominantly a solid growth pattern (46.7 %) or a similar
      proportion of solid and cribriform patterns (46.7 %). Eosinophilic amorphous
      material ("tumor droplets") was found in all cases (100 %). Most tumors showed
      duct-like spaces (93.3 %) and convoluted structures (60.0 %) whereas a minor
      proportion of cases presented calcifying epithelial odontogenic tumor (CEOT)-like
      areas (26.7 %). Variable amounts of calcified material were found in most AOTs
      (80.0 %) whereas osteodentin and perivascular hyalinization were seen only rarely
      (6.7 % each one). Five (33.3 %) cases had areas mimicking a dentigerous cyst and
      most of these were diagnosed in females (80.0 %). Regarding the histopathologic
      features, our results suggest that AOTs usually show predominance of solid
      pattern or a similar proportion of solid and cribriform patterns while
      osteodentin and perivascular hyalinization are rarely seen in these tumors. In
      addition, areas mimicking a dentigerous cyst and CEOT-like areas are relatively
      infrequent findings in AOTs.

PMID- 22869359
TI  - Pituitary function: Mitotane--safe and effective for Cushing disease?

PMID- 22869357
TI  - A case of age-related Epstein-Barr virus (EBV)-associated B cell
      lymphoproliferative disorder, so-called polymorphous subtype, of the mandible,
      with a review of the literature.
AB  - Epstein-Barr virus (EBV) is known to be associated with the development of
      lymphomas in immunocompromised patients. Recently, age-related immune impairment
      has been recognized as a predisposing factor in the development of EBV-driven
      lymphoproliferative disorders (LPDs) in elderly patients without any known
      immunodeficiency or prior lymphoma. In approximately 70% of reported cases, the
      affected sites have been extranodal, such as the skin, lung, tonsil and stomach.
      However, age-related EBV-associated B cell (EBV + B cell) LPD is extremely rare
      in the oral cavity. Here we report a 71-year-old Japanese man who developed an
      EBV + B cell LPD resembling classical Hodgkin lymphoma (CHL)--so-called
      polymorphous subtype-of the mandible. Histopathologically, infiltration of large
      atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells into
      granulation tissue with marked necrosis was found in the mandibular bone.
      Immunohistochemical analysis revealed that the large atypical Hodgkin or Reed
      Sternberg-like cells were CD3-, CD15-, CD20+, CD30+ and Epstein-Barr virus (EBV)
      latent infection membrane protein-1 (LMP-1)+. In situ hybridization (ISH)
      demonstrated EBV-encoded small RNA (EBER) + in numerous Hodgkin or Reed-Sternberg
      like cells. EBNA-2 was detected by polymerase chain reaction (PCR) using an
      extract from the formalin-fixed, paraffin-embedded specimen. To our knowledge,
      this is the first reported case of the polymorphous subtype of age-related EBV +
      B cell LPD affecting the mandible.

PMID- 22869360
TI  - Cancer: Pasireotide-relief in advanced NETs.

PMID- 22869361
TI  - Pituitary gland: New pathways in the pathogenesis of pituitary adenomas.

PMID- 22869362
TI  - Thyroid function: quitting smoking-transient risk of autoimmune hypothyroidism.

PMID- 22869366
TI  - A simple model for the pore size distribution in random fibre networks.
AB  - A heuristic approach based upon excluded volume arguments is developed for
      modelling the distribution of pore sizes in isotropic networks of randomly
      distributed cylindrical fibres. Our formalism accounts for the finite hard core
      diameters of the fibres, and leads to compact, analytically tractable expressions
      that span the complete range of volume fractions. Results are presented for the
      mean and mean-squared pore radii as functions of the fibre volume fraction, and
      for the partition coefficient of a spherical tracer particle into such a network
      under conditions such that steric effects are dominant.

PMID- 22869367
TI  - Development and application of a reverse transcription loop-mediated isothermal
      amplification method for rapid detection of Duck hepatitis A virus type 1.
AB  - We developed and evaluated a reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for detecting Duck hepatitis A virus type 1 (DHAV
      1). The amplification could be finished in 1 h under isothermal conditions at 63 
      degrees C by employing a set of four primers targeting the 2C gene of DHAV-1. The
      RT-LAMP assay showed higher sensitivity than the RT-PCR with a detection limit of
      0.1 ELD(50) 0.1 ml(-1) of DHAV-1. The RT-LAMP assay was highly specific; no cross
      reactivity was observed from the samples of other related viruses, bacteria,
      allantoic fluid of normal chicken embryos, or the livers of uninfected ducks.
      Thirty clinical samples were subjected to detection by RT-LAMP, RT-PCR, and virus
      isolation, which obtained completely consistent, positive results. As a simple,
      rapid, and accurate detection method, this RT-LAMP assay has important potential
      applications in the clinical diagnosis of DHAV-1.

PMID- 22869368
TI  - Osterix regulates calcification and degradation of chondrogenic matrices through
      matrix metalloproteinase 13 (MMP13) expression in association with transcription
      factor Runx2 during endochondral ossification.
AB  - Endochondral ossification is temporally and spatially regulated by several
      critical transcription factors, including Sox9, Runx2, and Runx3. Although the
      molecular mechanisms that control the late stages of endochondral ossification
      (e.g. calcification) are physiologically and pathologically important, these
      precise regulatory mechanisms remain unclear. Here, we demonstrate that Osterix
      is an essential transcription factor for endochondral ossification that functions
      downstream of Runx2. The global and conditional Osterix-deficient mice studied
      here exhibited a defect of cartilage-matrix ossification and matrix vesicle
      formation. Importantly, Osterix deficiencies caused the arrest of endochondral
      ossification at the hypertrophic stage. Microarray analysis revealed that matrix
      metallopeptidase 13 (MMP13) is an important target of Osterix. We also showed
      that there exists a physical interaction between Osterix and Runx2 and that these
      proteins function cooperatively to induce MMP13 during chondrocyte
      differentiation. Most interestingly, the introduction of MMP13 stimulated the
      calcification of matrices in Osterix-deficient mouse limb bud cells. Our results
      demonstrated that Osterix was essential to endochondral ossification and revealed
      that the physical and functional interaction between Osterix and Runx2 were
      necessary for the induction of MMP13 during endochondral ossification.

PMID- 22869369
TI  - On the roles and regulation of chondroitin sulfate and heparan sulfate in
      zebrafish pharyngeal cartilage morphogenesis.
AB  - The present study addresses the roles of heparan sulfate (HS) proteoglycans and
      chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal
      cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired
      biosynthesis of both HS and CS because of defective formation of the common
      proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3
      mutants, predicted to have defective HS polymerization. Notably, the effects on
      HS and CS biosynthesis in the respective mutant strains were shown to differ from
      what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS
      was shown to be virtually abolished, whereas these mutants still were capable of
      synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on
      the other hand were shown to synthesize reduced amounts of hypersulfated HS.
      Further, extl3 mutants produced higher levels of CS than control larvae, whereas
      morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS
      biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins
      influences the HS/CS ratio. A characterization of the pharyngeal cartilage
      element morphologies in the single mutant strains, as well as in ext2;uxs1 double
      mutants, was conducted. A correlation between HS and CS production and phenotypes
      was found, such that impaired HS biosynthesis was shown to affect chondrocyte
      intercalation, whereas impaired CS biosynthesis inhibited formation of the
      extracellular matrix surrounding chondrocytes.

PMID- 22869370
TI  - A novel mechanism for antibody-based anthrax toxin neutralization: inhibition of
      prepore-to-pore conversion.
AB  - Protective antigen (PA), a key component of anthrax toxin, mediates the entry of
      lethal factor (LF) or edema factor (EF) through a membranal pore into target
      cells. We have previously reported the isolation and chimerization of cAb29, an
      anti-PA monoclonal antibody that effectively neutralizes anthrax toxin in an
      unknown mechanism. The aim of this study was to elucidate the neutralizing
      mechanism of this antibody in vitro and to test its ability to confer post
      exposure protection against anthrax in vivo. By systematic evaluation of the
      steps taking place during the PA-based intoxication process, we found that cAb29
      did not interfere with the initial steps of intoxication, namely its ability to
      bind to the anthrax receptor, the consecutive proteolytic cleavage to PA(63),
      oligomerization, prepore formation, or LF binding. However, the binding of cAb29
      to the prepore prevented its pH-triggered transition to the transmembranal pore,
      thus preventing the last step of intoxication, i.e. the translocation of LF/EF
      into the cell. Epitope mapping, using a phage display peptide library, revealed
      that cAb29 binds the 2alpha(1) loop in domain 2 of PA, a loop that undergoes
      major conformational changes during pore formation. In vivo, we found that 100%
      of anthrax-infected rabbits survived when treated with cAb29 12 h after exposure.
      In conclusion, these experiments demonstrate that cAb29 exerts its potent
      neutralizing activity in a unique manner by blocking the prepore-to-pore
      conversion process.

PMID- 22869371
TI  - Structural framework for covalent inhibition of Clostridium botulinum neurotoxin
      A by targeting Cys165.
AB  - Clostridium botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins
      for humans and a major biothreat agent. Despite intense chemical efforts over the
      past 10 years to develop inhibitors of its catalytic domain (catBoNT/A), highly
      potent and selective inhibitors are still lacking. Recently, small inhibitors
      were reported to covalently modify catBoNT/A by targeting Cys(165), a residue
      located in the enzyme active site just above the catalytic zinc ion. However, no
      direct proof of Cys(165) modification was reported, and the poor accessibility of
      this residue in the x-ray structure of catBoNT/A raises concerns about this
      proposal. To clarify this issue, the functional role of Cys(165) was first
      assessed through a combination of site-directed mutagenesis and structural
      studies. These data suggested that Cys(165) is more involved in enzyme catalysis
      rather than in structural property. Then by peptide mass fingerprinting and x-ray
      crystallography, we demonstrated that a small compound containing a sulfonyl
      group acts as inhibitor of catBoNT/A through covalent modification of Cys(165).
      The crystal structure of this covalent complex offers a structural framework for
      developing more potent covalent inhibitors catBoNT/A. Other zinc metalloproteases
      can be founded in the protein database with a cysteine at a similar location,
      some expressed by major human pathogens; thus this work should find broader
      applications for developing covalent inhibitors.

PMID- 22869372
TI  - Role of binding and nucleoside diphosphate kinase A in the regulation of the
      cystic fibrosis transmembrane conductance regulator by AMP-activated protein
      kinase.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel
      mutations cause cystic fibrosis lung disease. A better understanding of CFTR
      regulatory mechanisms could suggest new therapeutic strategies. AMP-activated
      protein kinase (AMPK) binds to and phosphorylates CFTR, attenuating PKA-activated
      CFTR gating. However, the requirement for AMPK binding to CFTR and the potential
      role of other proteins in this regulation are unclear. We report that nucleoside
      diphosphate kinase A (NDPK-A) interacts with both AMPK and CFTR in overlay blots
      of airway epithelial cell lysates. Binding studies in Xenopus oocytes and
      transfected HEK-293 cells revealed that a CFTR peptide fragment that binds AMPK
      (CFTR-1420-57) disrupted the AMPK-CFTR interaction. Introduction of CFTR-1420-57
      into human bronchial Calu-3 cells enhanced forskolin-stimulated whole cell
      conductance in patch clamp measurements. Similarly, injection of CFTR-1420-57
      into Xenopus oocytes blocked the inhibition of cAMP-stimulated CFTR conductance
      by AMPK in two-electrode voltage clamp studies. AMPK also inhibited CFTR
      conductance with co-expression of WT NDPK-A in two-electrode voltage clamp
      studies, but co-expression of a catalytically inactive H118F mutant or various
      Ser-120 NDPK-A mutants prevented this inhibition. In vitro phosphorylation of WT
      NDPK-A was enhanced by purified active AMPK, but phosphorylation was prevented in
      H118F and phosphomimic Ser-120 NDPK-A mutants. AMPK does not appear to
      phosphorylate NDPK-A directly but rather promotes an NDPK-A autophosphorylation
      event that involves His-118 and Ser-120. Taken together, these results suggest
      that NDPK-A exists in a functional cellular complex with AMPK and CFTR in airway
      epithelia, and NDPK-A catalytic function is required for the AMPK-dependent
      regulation of CFTR.

PMID- 22869373
TI  - Cholesterol through the looking glass: ability of its enantiomer also to elicit
      homeostatic responses.
AB  - How cholesterol is sensed to maintain homeostasis has been explained by direct
      binding to a specific protein, Scap, or through altering the physical properties
      of the membrane. The enantiomer of cholesterol (ent-cholesterol) is a valuable
      tool in distinguishing between these two models because it shares nonspecific
      membrane effects with native cholesterol (nat-cholesterol), but not specific
      binding interactions. This is the first study to compare ent- and nat-cholesterol
      directly on major molecular parameters of cholesterol homeostasis. We found that
      ent-cholesterol suppressed activation of the master transcriptional regulator of
      cholesterol metabolism, SREBP-2, almost as effectively as nat-cholesterol.
      Importantly, ent-cholesterol induced a conformational change in the cholesterol
      sensing protein Scap in isolated membranes in vitro, even when steps were taken
      to eliminate potential confounding effects from endogenous cholesterol. Ent
      cholesterol also accelerated proteasomal degradation of the key cholesterol
      biosynthetic enzyme, squalene monooxygenase. Together, these findings provide
      compelling evidence that cholesterol maintains its own homeostasis not only via
      direct protein interactions, but also by altering membrane properties.

PMID- 22869374
TI  - Pharmacological modulation of the retinal unfolded protein response in Bardet
      Biedl syndrome reduces apoptosis and preserves light detection ability.
AB  - Ciliopathies, a class of rare genetic disorders, present often with retinal
      degeneration caused by protein transport defects between the inner segment and
      the outer segment of the photoreceptors. Bardet-Biedl syndrome is one such
      ciliopathy, genetically heterogeneous with 17 BBS genes identified to date,
      presenting early onset retinitis pigmentosa. By investigating BBS12-deprived
      retinal explants and the Bbs12(-/-) murine model, we show that the impaired
      intraciliary transport results in protein retention in the endoplasmic reticulum.
      The protein overload activates a proapoptotic unfolded protein response leading
      to a specific Caspase12-mediated death of the photoreceptors. Having identified a
      therapeutic window in the early postnatal retinal development and through
      optimized pharmacological modulation of the unfolded protein response, combining
      three specific compounds, namely valproic acid, guanabenz, and a specific
      Caspase12 inhibitor, achieved efficient photoreceptor protection, thereby
      maintaining light detection ability in vivo.

PMID- 22869375
TI  - Calcium currents are enhanced by alpha2delta-1 lacking its membrane anchor.
AB  - The accessory alpha(2)delta subunits of voltage-gated calcium channels are
      membrane-anchored proteins, which are highly glycosylated, possess multiple
      disulfide bonds, and are post-translationally cleaved into alpha(2) and delta.
      All alpha(2)delta subunits have a C-terminal hydrophobic, potentially trans
      membrane domain and were described as type I transmembrane proteins, but we found
      evidence that they can be glycosylphosphatidylinositol-anchored. To probe further
      the function of membrane anchoring in alpha(2)delta subunits, we have now
      examined the properties of alpha(2)delta-1 constructs truncated at their putative
      glycosylphosphatidylinositol anchor site, located before the C-terminal
      hydrophobic domain (alpha(2)delta-1DeltaC-term). We find that the majority of
      alpha(2)delta-1DeltaC-term is soluble and secreted into the medium, but
      unexpectedly, some of the protein remains associated with detergent-resistant
      membranes, also termed lipid rafts, and is extrinsically bound to the plasma
      membrane. Furthermore, heterologous co-expression of alpha(2)delta-1DeltaC-term
      with Ca(V)2.1/beta1b results in a substantial enhancement of the calcium channel
      currents, albeit less than that produced by wild-type alpha(2)delta-1. These
      results call into question the role of membrane anchoring of alpha(2)delta
      subunits for calcium current enhancement.

PMID- 22869376
TI  - Structural basis for the Golgi association by the pleckstrin homology domain of
      the ceramide trafficking protein (CERT).
AB  - Ceramide transport from the endoplasmic reticulum to the Golgi apparatus is
      crucial in sphingolipid biosynthesis, and the process relies on the ceramide
      trafficking protein (CERT), which contains pleckstrin homology (PH) and StAR
      related lipid transfer domains. The CERT PH domain specifically recognizes
      phosphatidylinositol 4-monophosphate (PtdIns(4)P), a characteristic
      phosphoinositide in the Golgi membrane, and is indispensable for the endoplasmic
      reticulum-to-Golgi transport of ceramide by CERT. In this study, we determined
      the three-dimensional structure of the CERT PH domain by using solution NMR
      techniques. The structure revealed the presence of a characteristic basic groove
      near the canonical PtdIns(4)P recognition site. An extensive interaction study
      using NMR and other biophysical techniques revealed that the basic groove
      coordinates the CERT PH domain for efficient PtdIns(4)P recognition and
      localization in the Golgi apparatus. The notion was also supported by Golgi
      mislocalization of the CERT mutants in living cells. The distinctive binding
      modes reflect the functions of PH domains, as the basic groove is conserved only
      in the PH domains involved with the PtdIns(4)P-dependent lipid transport activity
      but not in those with the signal transduction activity.

PMID- 22869377
TI  - High immunogenicity of the human leukocyte antigen peptidomes of melanoma tumor
      cells.
AB  - Human leukocyte antigens (HLA) bind peptides generated by limited proteolysis in
      cells and present them at the cell surfaces for recognition by T cells. Through
      this antigen presentation function they control the specificity of T cell
      responses and thereby adaptive immune responses. Knowledge of HLA-bound peptides
      is thus key to understanding adaptive immunity and to the development of vaccines
      and other specific immune intervention strategies. To gain insight into the
      antigenicity of melanomas, peptides were extracted from HLA isolated from the
      tumor cells, separated by two-dimensional HPLC, and sequenced by mass
      spectrometry. The spectra were analyzed by database-dependent MASCOT searches and
      database-independent de novo sequencing and, where required, confirmed with
      synthetic peptides, which were also used to determine their immunogenicity.
      Comparing four different melanoma cell lines, little overlap of the HLA-bound
      peptides was found, suggesting a high degree of individualization of the HLA
      peptidomes. This notwithstanding, the peptidomes were highly immunogenic in the
      patients from whom the tumor cells had been established and in unrelated
      patients. This broad cross-patient immunogenicity was only exceptionally related
      to individual peptides. The majority of the identified epitopes were derived from
      low to medium abundance proteins, mostly involved in sensitive cellular processes
      such as cell cycle control, DNA replication, control of gene expression, tumor
      suppressor function, and protein metabolism. The peptidomes thus provide insights
      into processes potentially related to tumorigenesis. Furthermore, analyses of the
      peptide sequences yield information on the specificity of peptide selection by
      HLA applicable to the developing prediction algorithms for T cell epitopes.

PMID- 22869378
TI  - Conformational flexibility determines selectivity and antibacterial,
      antiplasmodial, and anticancer potency of cationic alpha-helical peptides.
AB  - We used a combination of fluorescence, circular dichroism (CD), and NMR
      spectroscopies in conjunction with size exclusion chromatography to help
      rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities
      of a series of proline-free and proline-containing model antimicrobial peptides
      (AMPs) in terms of their structural properties. When compared with proline-free
      analogs, proline-containing peptides had greater activity against Gram-negative
      bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium
      falciparum, which they were capable of killing without causing hemolysis. In
      contrast, incorporation of proline did not have a consistent effect on peptide
      activity against Mycobacterium tuberculosis. In membrane-mimicking environments,
      structures with high alpha-helix content were adopted by both proline-free and
      proline-containing peptides. In solution, AMPs generally adopted disordered
      structures unless their sequences comprised more hydrophobic amino acids or until
      coordinating phosphate ions were added. Proline-containing peptides resisted
      ordering induced by either method. The roles of the angle subtended by positively
      charged amino acids and the positioning of the proline residues were also
      investigated. Careful positioning of proline residues in AMP sequences is
      required to enable the peptide to resist ordering and maintain optimal
      antibacterial activity, whereas varying the angle subtended by positively charged
      amino acids can attenuate hemolytic potential albeit with a modest reduction in
      potency. Maintaining conformational flexibility improves AMP potency and
      selectivity toward bacterial, plasmodial, and cancerous cells while enabling the
      targeting of intracellular pathogens.

PMID- 22869379
TI  - Estrogen facilitates spinal cord synaptic transmission via membrane-bound
      estrogen receptors: implications for pain hypersensitivity.
AB  - Recent evidence suggests that estrogen is synthesized in the spinal dorsal horn
      and plays a role in nociceptive processes. However, the cellular and molecular
      mechanisms underlying these effects remain unclear. Using electrophysiological,
      biochemical, and morphological techniques, we here demonstrate that 17beta
      estradiol (E2), a major form of estrogen, can directly modulate spinal cord
      synaptic transmission by 1) enhancing NMDA receptor-mediated synaptic
      transmission in dorsal horn neurons, 2) increasing glutamate release from primary
      afferent terminals, 3) increasing dendritic spine density in cultured spinal cord
      dorsal horn neurons, and 4) potentiating spinal cord long term potentiation (LTP)
      evoked by high frequency stimulation (HFS) of Lissauer's tract. Notably, E2-BSA,
      a ligand that acts only on membrane estrogen receptors, can mimic E2-induced
      facilitation of HFS-LTP, suggesting a nongenomic action of this neurosteroid.
      Consistently, cell surface biotinylation demonstrated that three types of ERs
      (ERalpha, ERbeta, and GPER1) are localized on the plasma membrane of dorsal horn
      neurons. Furthermore, the ERalpha and ERbeta antagonist ICI 182,780 completely
      abrogates the E2-induced facilitation of LTP. ERbeta (but not ERalpha) activation
      can recapitulate E2-induced persistent increases in synaptic transmission (NMDA
      dependent) and dendritic spine density, indicating a critical role of ERbeta in
      spinal synaptic plasticity. E2 also increases the phosphorylation of ERK, PKA,
      and NR2B, and spinal HFS-LTP is prevented by blockade of PKA, ERK, or NR2B
      activation. Finally, HFS increases E2 release in spinal cord slices, which can be
      prevented by aromatase inhibitor androstatrienedione, suggesting activity
      dependent local synthesis and release of endogenous E2.

PMID- 22869380
TI  - Structural basis for paxillin binding and focal adhesion targeting of beta
      parvin.
AB  - beta-Parvin is a cytoplasmic adaptor protein that localizes to focal adhesions
      where it interacts with integrin-linked kinase and is involved in linking
      integrin receptors to the cytoskeleton. It has been reported that despite high
      sequence similarity to alpha-parvin, beta-parvin does not bind paxillin,
      suggesting distinct interactions and cellular functions for these two closely
      related parvins. Here, we reveal that beta-parvin binds directly and specifically
      to leucine-aspartic acid repeat (LD) motifs in paxillin via its C-terminal
      calponin homology (CH2) domain. We present the co-crystal structure of beta
      parvin CH2 domain in complex with paxillin LD1 motif to 2.9 A resolution and find
      that the interaction is similar to that previously observed between alpha-parvin
      and paxillin LD1. We also present crystal structures of unbound beta-parvin CH2
      domain at 2.1 A and 2.0 A resolution that show significant conformational
      flexibility in the N-terminal alpha-helix, suggesting an induced fit upon
      paxillin binding. We find that beta-parvin has specificity for the LD1, LD2, and
      LD4 motifs of paxillin, with K(D) values determined to 27, 42, and 73 MUM,
      respectively, by surface plasmon resonance. Furthermore, we show that proper
      localization of beta-parvin to focal adhesions requires both the paxillin and
      integrin-linked kinase binding sites and that paxillin is important for early
      targeting of beta-parvin. These studies provide the first molecular details of
      beta-parvin binding to paxillin and help define the requirements for beta-parvin
      localization to focal adhesions.

PMID- 22869381
TI  - Effect of combined topical heparin and steroid on corneal neovascularization in
      children.
AB  - BACKGROUND AND OBJECTIVE: To demonstrate the effect of topical heparin combined
      with topical steroid on corneal neovascularization (CN) in children. PATIENTS AND
      METHODS: Four children (5 eyes) with new-onset progressive CN in at least one eye
      received topical rimexolone or dexamethasone in combination with heparin until
      complete regression of CN was obtained. The regression of CN was documented by
      slit-lamp or anterior segment photography. RESULTS: All 5 eyes showed complete
      regression of CN within 5 months. An anti-angiogenic effect was found as early as
      1 week after starting topical combination treatment. No ocular and systemic side
      effects were detected and treatment was well tolerated by all children. In the 3
      eyes with involvement of the optical axis, symmetrical visual acuity was obtained
      by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6
      months, respectively, after ending combination therapy. Both eyes responded
      favorably to re-treatment. CONCLUSION: Combination of topical heparin and steroid
      leads to rapid regression and complete inactivity of CN. This therapeutic
      approach is promising, especially in children with limited therapeutic
      alternatives and a high risk for amblyopia.

PMID- 22869382
TI  - Morphometric analysis of epiretinal membranes using SD-OCT.
AB  - BACKGROUND AND OBJECTIVE: To determine whether the volumes of macular layers
      before and after epiretinal membrane (ERM) peeling as measured by spectral-domain
      optical coherence tomography (SD-OCT) correlated with best-corrected visual
      acuity (BCVA) or ERM location. PATIENTS AND METHODS: Thirty-six eyes with
      idiopathic ERM and 12 control eyes were imaged preoperatively and postoperatively
      using SD-OCT. The inner, middle, and outer retinal layers were measured in the
      temporal and nasal half of the central 1,500 MUm of the macula for each of the SD
      OCT five raster scans and used to estimate the volumes for each group. RESULTS:
      The inner layer volumes were larger in cases compared with control eyes. The
      nasal inner and temporal inner layer volumes decreased after ERM removal in the
      nasal dominant, macular dominant, and temporal dominant groups. The inner layer
      volume decreased more temporally than nasally in the macular dominant and
      temporal dominant groups but not in the nasal dominant group. The volume
      decreased more in the temporal middle than the nasal middle layer for the
      temporal dominant group. The BCVA improvement correlated with nasal inner layer
      volume decrease and nasal outer and temporal outer layer volume increase.
      CONCLUSION: The volume of the inner perifoveal retinal sections decreases after
      ERM peeling, possibly representing resolution of edema or reorganization of the
      nerve fiber layer on release of mechanical traction. Visual improvement
      correlated with volume increase of the outer retinal layers and may represent
      photoreceptor cell recovery after ERM peeling.

PMID- 22869383
TI  - Comparison of postoperative refractive outcomes: IOLMaster(r) versus immersion
      ultrasound.
AB  - BACKGROUND AND OBJECTIVE: To compare the postoperative refractive outcomes
      between IOLMaster biometry (Carl Zeiss Meditec, Inc., Dublin, CA) and immersion
      ultrasound biometry for axial length measurements. PATIENTS AND METHODS:
      Refractive outcomes in 354 eyes were compared using the IOLMaster and the
      immersion ultrasound biometry. Predicted refraction was determined using manual
      keratometry and the SRK-T formula with personalized A-constant. RESULTS: The
      axial lengths measured using the IOLMaster and immersion ultrasound were 24.49 +/
      2.11 and 24.46 +/- 2.11 mm, respectively, and the difference was significant (P
      < .05). The mean errors were 0.000 +/- 0.578 D with the IOLMaster, and 0.000 +/-
      0.599 D with the immersion ultrasound, but the difference was not significant.
      The mean absolute error was smaller with the IOLMaster than with immersion
      ultrasound (0.463 +/- 0.341 vs 0.479 +/- 0.359 D), but the difference was not
      significant. CONCLUSION: IOLMaster biometry yields highly accurate results in
      cataract surgery. However, if the IOLMaster is unavailable, immersion ultrasound
      biometry with personalized intraocular lens constants is an acceptable
      alternative.

PMID- 22869384
TI  - Rationale for performing penetrating keratoplasty rather than DSAEK in patients
      with bullous keratopathy in Japan.
AB  - BACKGROUND AND OBJECTIVE: To analyze the rationale for performing penetrating
      keratoplasty (PK) rather than Descemet's stripping automated endothelial
      keratoplasty (DSAEK) in patients with bullous keratopathy (BK) in Japan. PATIENTS
      AND METHODS: A total of 136 eyes of 130 patients with consecutive BK were
      enrolled. Patients treated by DSAEK were categorized as the DSAEK group. The
      remaining patients were considered unsuitable for DSAEK due to the presence of
      risk factors, and were treated by PK (PK group). In both groups, the number of
      the patients and the causes of BK were analyzed. Also, specifically in the PK
      group, the reasons for not performing DSAEK were analyzed. RESULTS: The causes of
      BK differed significantly between the two groups (P < .001). Risk factors
      considered unsuitable for DSAEK include significant stromal scarring, iris
      abnormalities, and lens abnormalities. CONCLUSION: For successful DSAEK, risk
      factors and contraindications should be carefully evaluated before surgery.

PMID- 22869385
TI  - Ablating the anteroseptal accessory pathway-ablation via the right internal
      jugular vein may improve safety and efficacy.
AB  - PURPOSE: Ablation of anteroseptal accessory pathways have historically been
      associated with lower success rates and a higher risk of AV nodal injury due to
      close proximity to the compact AV node. We describe the technique of ablation of
      anteroseptal APs via the right internal jugular vein (RIJV). METHODS: A
      retrospective analysis of all patients undergoing EP study and ablation at the
      Children's Hospital at Montefiore from 2008 to 2011 for SVT and/or WPW was
      performed. All patients less than 21 years of age who underwent ablation from the
      RIJV for either WPW or a concealed accessory pathway located in the anteroseptal
      region were included. RESULTS: A total of 16 patients met inclusion criteria and
      were the subject of this analysis. Twelve patients had WPW (75%) and four had a
      concealed AP (25%). Ablation was acutely successful in 94% of patients (15/16).
      In one patient, ablation was deferred due to close proximity to the compact AV
      node and risk of AV nodal injury. Radiofrequency (RF) was used in 14 patients and
      cryoenergy in two patients. There was no difference in WB CL pre- and post
      ablation (p = 0.19). There were no complications encountered. At a mean follow-up
      of 15 +/- 12 months, there were no recurrences. CONCLUSION: Ablation of APs in
      the right anteroseptal region can safely and effectively be performed via the
      RIJV with a success rate of 94%. This technique should be considered for ablation
      of APs located in the anterior septum.

PMID- 22869386
TI  - Active fixation mechanism complicates coronary sinus lead extraction and limits
      subsequent reimplantation targets.
AB  - INTRODUCTION: Implantation of cardiac resynchronization therapy (CRT) devices is
      technically challenging and can be limited by lead dislodgement. The Attain
      Starfix active fixation coronary sinus (CS) lead (model 4195, Medtronic,
      Minneapolis, MN, USA) was introduced to reduce the rate of lead dislodgement, but
      the active fixation mechanism presents additional difficulties should these leads
      require extraction. METHODS: CS lead extraction procedures at our institution
      from 2003 to 2011 were reviewed. Procedural variables were compared between
      extraction of the Starfix lead and passive fixation CS leads. Attempts at
      reimplantation post Starfix lead extraction were examined. RESULTS: Four Starfix
      CS leads were extracted in four patients during this time period. The mean
      implant duration was 784 days (range, 392-1,029 days). The indication for
      extraction was infection in all four cases. Mean total procedure time was 141.5
      min (range, 92-205 min). None of the fixation lobes could be retracted in one
      lead and only the most proximal lobes could be retracted in the remaining three
      leads. All four leads were removed in their entirety. The excimer laser sheath
      (Spectranetics Laser Sheath II, Spectranetics Corp., Colorado Springs, CO,USA)
      was required to remove the lead in all 4 cases (100 %) compared to 25 of 131
      (19.1 %) of passive fixation CS lead extractions (mean implant duration, 659 +/-
      697 days) performed at our institution over the same time period (P < 0.001). In
      three cases, the laser sheath had to be advanced past the CS ostium to remove the
      Starfix lead. After extraction, fibrous material which had grown between the
      lobes of the fixation mechanism was noted in all four cases. No complications
      occurred. Transvenous CS lead reimplantation was attempted at a median of 7.5
      days post extraction in all four patients. The original target branch was
      occluded in three patients and the main CS in one patient. Reimplantation was
      successful in another branch of the CS in three of four patients; one underwent
      minimally invasive epicardial lead placement. CONCLUSIONS: The Starfix active
      fixation CS lead presents additional procedural complexity and uniform use of
      excimer laser sheath compared to other CS leads. Reimplantation was not possible
      in the same venous branch in our experience.

PMID- 22869388
TI  - Predictors of left atrium appendage clot detection despite on-target warfarin
      prevention for atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: The antithrombotic management of atrial fibrillation (AF)
      is currently based on clinical scores (CHADS(2) or CHA(2)DS(2)VASc). The
      prevalence of left atrium (LA) thrombi in effectively anticoagulated AF patients
      has been reported as being up to 7.7 %. We tried to correlate LA/LA appendage
      (LAA) thrombus detection with possible clinical predictors in warfarin-treated
      patients. METHODS: We performed trans-esophageal echocardiography on 430 patients
      (mean age, 60.3 +/- 9.8 years) receiving oral anticoagulant (OAC) therapy and
      undergoing pulmonary vein isolation. In 10/430 (2.3 %), an LA thrombus was found
      despite therapeutic OAC (mean INR 2.6 +/- 0.6; range, 2.0-3.8) over the previous
      4 weeks. RESULTS: Two study groups were identified: 1. T-positive group = with
      LAA thrombus (10 patients) 2. T-negative group = without LAA thrombus (420
      patients) The T-positive patients had a higher CHADS(2) score (1.5 +/- 0.7 versus
      0.7 +/- 0.8; p = 0.004), a lower LVEF (54.7 +/- 9.5 % versus 60.2 +/- 7.4; p =
      0.02), and a larger LA size (LA diameter, 56 +/- 12.2 mm versus 46 +/- 6.5 mm; p 
      < 0.001and normalized LA volume: 140.2 +/- 66 ml/m2 vs. 67 +/- 39 ml/m2; p <
      0.05). On multivariate analysis, a larger LA diameter and normalized LA volume
      (OR, 1.14; 95 % C.I., 1.04-1.26; p = 0.006 and OR, 1.02; 95 % C.I., 1.01-1.03; p
      = 0.001, respectively) and a higher CHA(2)DS(2)VASc score (OR, 2.4; 95 % C.I.,
      1.4-4.2; p = 0.001) predicted left atrium appendage (LAA) thrombus. In another
      42/430 (9.8 %) patients, an LA spontaneous echo-contrast (SEC) was detected.
      Thus, cumulatively, 52/430 (12.1 %) patients had either LAA thrombi (10 patients)
      or SEC (42 patients). LA diameter continued to predict the presence of either
      thrombi or SEC (OR, 1.14; 95 % C.I., 1.07-1.2; p < 0.05). CONCLUSIONS: We found a
      2.3 % prevalence of LA thrombus (12.1 % when SEC was also considered). The
      thrombus was present despite on-target warfarin prevention. In addition to a
      higher CHA(2)DS(2)VASc score, a larger LA size was a strong predictor of clot
      detection.

PMID- 22869389
TI  - A comparison of bleeding complications post-ablation between warfarin and
      dabigatran.
AB  - INTRODUCTION: Although warfarin has traditionally been used for reducing risk of
      stroke in patients with atrial fibrillation, over the past year, the direct
      thrombin inhibitor dabigatran has become an accepted alternative. No study has
      conclusively investigated bleeding risks of patients treated with dabigatran
      immediately following radiofrequency catheter ablation (RFCA) procedures.
      METHODS: We evaluated 156 consecutive patients referred for RFCA of atrial
      arrhythmias: 31 patients were on dabigatran and 125 patients were on warfarin.
      The incidence of bleeding complications during the first 48 h and the first week
      following ablation were recorded and comparisons made using Fisher's exact test.
      Major complications were defined as hemorrhage requiring blood products or the
      need for vascular intervention. Minor complications were defined as prolonged
      bleeding from the catheter insertion site, hematoma formation, or development of
      ecchymosis. Our study also took into account the intraprocedure activated
      clotting time (ACT) levels in an effort to describe any differences between both
      patient groups. RESULTS: There were no differences in age, gender, procedure
      type, or level of intraprocedural anticoagulation between the warfarin and
      dabigatran groups. No major bleeding complications were observed in either
      patient group at either 48 h or 1 week postprocedure. Six of the 31 dabigatran
      patients and 21 of the 125 warfarin patients had minor bleeding complications.
      There was no statistically significant difference between the incidence of minor
      bleeding complications between the two groups (p = 0.7384), although rebleeding
      was more commonly observed in patients on dabigatran. In regard to the
      intraprocedure ACT levels, there was more variability in the dabigatran patient
      group, and it was more difficult to achieve the goal ACT level, yet these results
      did not affect overall bleeding complications. CONCLUSION: In our cohort,
      bleeding-related complications 48 h and 1 week post-ablation were similar for
      warfarin and dabigatran. Dabigatran is associated with more intraprocedural
      variability in ACT than warfarin.

PMID- 22869387
TI  - Clinical characteristics and acute results of catheter ablation for outflow tract
      ventricular tachycardia or premature beats.
AB  - PURPOSE: Contemporary outcome data of catheter ablation for outflow tract
      tachycardia (OTT) and ventricular premature beats (VPBs) are rare. The aim of
      this study was to describe the clinical characteristics, the acute procedure
      success rate, and the long-term survival of patients who underwent an ablation
      procedure for OTT or VPBs. METHODS: The study was a single-center retrospective
      cohort study. All 82 consecutive OTT and VPB first ablation procedures between
      1999 and 2009 were included. Patients with structural heart disease were
      excluded. RESULTS: Mean age was 46 +/- 13 years. Forty-three percent of the
      patients were male. All patients were alive after a median follow-up duration of
      31 months (interquartile range, 14-65 months). Eighty-nine percent suffered from
      palpitations and 12 % had a history of syncope. Ventricular tachycardia was
      documented in 73 % and monomorphic VPBs in 99 %. Seventy-three percent of the
      patients were ablated in the right ventricular outflow tract, 15 % in the left
      ventricular outflow tract, and 12 % in the coronary cusps. Radiofrequency energy
      was used in 95 % of the patients, cryo energy in 9 %. Acute success was achieved
      in 78 %. Six patients (7 %) experienced a complication (five pericardial
      effusions, one pseudo-aneurysm of the femoral artery). Three patients needed
      pericardiocentesis (4 %). CONCLUSION: Ablation for OTT and VPB is successful in
      the vast majority of cases, with a low but still existing complication rate. Long
      term survival was excellent, underscoring the benign nature of this arrhythmia.

PMID- 22869390
TI  - Implantable cardiac devices with patent foramen ovale--a risk factor for
      cardioembolic stroke?
AB  - A quarter of patients with implanted cardiac devices have a patent foramen ovale
      (PFO). Thrombus is frequently noted on intravascular leads that in the presence
      of a PFO could result in cerebral vascular embolic events. However, whether this
      mechanism of stroke occurs is not clearly known. We report three patients with
      PFO, implanted leads with thrombus, and stroke, including a patient where
      thrombus partially attached to the lead was seen traversing the PFO.

PMID- 22869391
TI  - Effect of renal sympathetic denervation on the inducibility of atrial
      fibrillation during rapid atrial pacing.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with activity of renin
      angiotensin-aldosterone system (RAAS). Reduction in renal noradrenaline spillover
      could be achieved after renal sympathetic denervation (RSD). The relationship
      between RSD and AF is unknown. OBJECTIVE: The objective of the study was to
      investigate the inducibility of AF during atrial rapid pacing after RSD. METHODS:
      Thirteen dogs were used for the study as follows: control group (seven dogs) and
      RSD group (six dogs). In the control group, dogs were subjected to atrial pacing
      at 800 beats/min for 7 h, and atrial effective refractory period (AERP) was
      measured every hour in the status of non-pacing. Subsequently, pacing was stopped
      and the burst pacing (500 bpm) was repeated to induce AF three times. In the RSD
      group, after each renal artery ablation, the procedure of pacing and
      electrophysiological measurement was exactly same as in the control group. Blood
      was collected before and after pacing to measure the levels of renin, angiotensin
      II and aldosterone. RESULTS: There was a persistent decrease in AERP in both
      groups. However, 7 h after cessation of pacing, the induced number of times and
      duration of AF were higher in the control group than that in the RSD group (1.0
      +/- 1.26 vs 3.14 +/- 2.54, P = 0.03; 16.5 +/- 25.1 vs 86.6 +/- 116.4, P = 0.02).
      The plasma aldosterone concentration increased significantly 7 h after rapid
      pacing in control group (renin, 119.8 +/- 31.1 vs 185.3 +/- 103.5 pg/ml, P <
      0.01; aldosterone, 288.2 +/- 43.1 vs 369.6 +/- 109.8 pg/ml, P = 0.01). The levels
      of renin and aldosterone showed a decreasing trend in RSD group, but this did not
      attain statistical significance. CONCLUSIONS: Episodes of AF could be decreased
      by renal sympathetic denervation during short-time rapid atrial pacing. This
      effect might have relationship with decreased activity of RAAS.

PMID- 22869392
TI  - Total mercury in Yellow Knights (Tricholoma equestre) mushrooms and beneath
      soils.
AB  - Mercury has been determined in caps, stipes and whole fruiting bodies of Yellow
      Knights mushrooms and the beneath top layer of soils from ten geographically
      distant locations in Poland. The Yellow Knights can be considered as an effective
      accumulator of total Hg. The mean values of bioconcentration factor (BCF) of Hg
      in caps of Yellow Knights for nine of the locations ranged from 22 +/- 9 to 75 +/
      13 (total range 9.0-90) and for stipes from 13 +/- 7 to 52 +/- 9 (total 4.4-93).
      The top layer (0-10 cm) of soils in these nine sites contained Hg with mean (+/
      SD) concentration ranging from 0.019 +/- 0.003 to 0.046 +/- 0.007 ng/g dry
      weight. Mercury was less accumulated (BCF 4.9 +/- 2.7 for a whole fruiting
      bodies) by Yellow Knights that emerged at the most contaminated site, where soil
      contained 0.059 +/- 0.028 ng Hg/g dw. The potential of Yellow Knights communities
      to bioconcentrate Hg (determined as BCF) in fruiting bodies varied between the
      localities more than tenfold and decreased highly with increase of Hg content of
      the top soil.

PMID- 22869393
TI  - Biomonitoring of metals in Ganga water at different ghats of Haridwar:
      implications of constructed wetland for sewage detoxification.
AB  - An assessment of Ganga river water quality at different ghats of Haridwar, showed
      high TDS (782.15 mg L(-1)) and BOD (21.76 mg L(-1)) levels at the mixing points
      of sewage discharge channels and the water was found to be contaminated with
      appreciable amounts of toxic metals; Cu, Pb, Zn, Cr and Mn (0.178, 0.566, 0.199,
      0.177 and 0.160 mg L(-1)). The Ganga water supported exuberant growth of algae
      and aquatic macrophytes in littoral zone of river, which accumulated appreciable
      amount of metals in their tissues. Results showed possibility of using metal
      accumulation potential of plants and algae for monitoring low level of metal
      contamination vis-a-vis their use in renovating sewage by treating into
      especially designed constructed wetland.

PMID- 22869394
TI  - Application of solid-phase microextraction method to determine bioavailable
      fraction of PAH in hazardous waste.
AB  - The solid-phase microextraction (SPME) method was developed to determine PAH free
      dissolved concentration (C(free)) in field leachates from hazardous waste
      disposal. SPME technique, involving a 100-MUm polydimethylsiloxane (PDMS) fiber
      coupled to GC-MS was optimized for determination of C(free). The following PAH
      were found in bioavailable form: acenaphthylene, acenaphthene, fluorene,
      phenanthrene, anthracene, fluoranthene, pyrene, with C(free) varying between 2.38
      and 62.35 ng/L. Conventional solvent extraction was used for measurement of total
      concentration (C(total)) in the same samples, and ranging from 1.26 to 77.56
      MUg/L. Determining C(free) of the hydrophobic toxic pollutants could give useful
      information for risk assessment of the hazardous waste.

PMID- 22869395
TI  - Characteristics of patients with chronic hepatitis C who develop hepatocellular
      carcinoma.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is the most frequent form of
      primary liver cancer and chronic infection with hepatitis C virus is one of the
      main risk factors for HCC. This study analyses the characteristics of the
      patients with chronic hepatitis C participating in the Swiss Hepatitis C Cohort
      Study who developed HCC. METHODS: Analysis of the database of the Swiss Hepatitis
      C Cohort Study, a multicentre study that is being carried out in eight major
      Swiss hospitals since the year 2000. Patients with chronic hepatitis C and HCC
      were regrouped and compared to the patients without HCC. RESULTS: Among the 3,390
      patients of the cohort, 130 developed an HCC. Age was one of the determining
      factors. Cirrhosis and its complications ascites and porto-systemic
      encephalopathy were associated with HCC. Males presented a higher risk for HCC
      than females. Alcohol consumption was associated with HCC. Diabetes mellitus was
      an important risk factor, especially in patients with low fibrosis. Patients with
      Hepatitis C genotype 2 had significantly less HCC than patients with other
      genotypes. A low socioeconomic status (income, education, profession) was
      associated with HCC. CONCLUSIONS: Beside the expected characteristics (age,
      gender, cirrhosis, alcohol), these data stress the role of diabetes mellitus and
      reveal the importance of low socioeconomic status as a risk factor for HCC in
      Swiss patients infected with hepatitis C virus. This vulnerable population should
      be closely monitored.

PMID- 22869396
TI  - The road less travelled...

PMID- 22869401
TI  - The darkening veil of "do everything".

PMID- 22869397
TI  - Do antenatal and postnatal parental psychological distress, and recognized need
      of help predict preadolescent's psychiatric symptoms? The Finnish Family
      Competence Cohort study.
AB  - In a prospective population-based study, mothers and fathers of 1,247 children
      reported their physical and mental health during pregnancy, after delivery,
      within the child's first 18 months of life, and at 12 years. Additionally,
      maternal health clinic nurses rated parents' well-being and perceived need for
      support. At age 12, child outcomes were also measured using CBCL and YSR
      externalizing and internalizing scales. Results indicate that both ante- and
      postnatal maternal distress predicted future externalizing problems in offspring.
      Conversely, fathers' postnatal distress predicted subsequent internalizing
      problems. Furthermore, mother's depressed mood in the first trimester best
      predicted the child's externalizing problems at age 12. Nurses's ratings of
      mother's antenatal and perinatal need for support, perinatal distress, and
      family's need for support were associated with both internalizing and
      externalizing problems at age 12. Maternal antenatal distress increases the risk
      of offspring's externalizing problems in preadolescense, and postnatal distress
      in either parent increases the risk of internalizing problems. Parental self
      reports and indirect ratings from health care providers during pregnancy and
      infancy may therefore reliably recognize offspring at risk for subsequent
      psychiatric symptomatology.

PMID- 22869402
TI  - Pediatric hospitalists: coming of age in 2012.

PMID- 22869403
TI  - Organized physical activity in young school children and subsequent 4-year change
      in body mass index.
AB  - OBJECTIVE: To determine whether participation in organized outdoor team sports
      and structured indoor nonschool activity programs in kindergarten and first grade
      predicted subsequent 4-year change in body mass index (BMI; calculated as weight
      in kilograms divided by height in meters squared) during the adiposity rebound
      period of childhood. DESIGN: Longitudinal cohort study. SETTING: Forty-five
      schools in 13 communities across Southern California. PARTICIPANTS: Largely
      Hispanic and non-Hispanic white children (N = 4550) with a mean (SD) age at study
      entry of 6.60 (0.65) years. MAIN EXPOSURES: Parents completed questionnaires
      assessing physical activity, demographic characteristics, and other relevant
      covariates at baseline. Data on built and social environmental variables were
      linked to the neighborhood around children's homes using geographical information
      systems. MAIN OUTCOME MEASURES: Each child's height and weight were measured
      annually during 4 years of follow-up. RESULTS: After adjusting for several
      confounders, BMI increased at a rate 0.05 unit/year slower for children who
      participated in outdoor organized team sports at least twice per week compared
      with children who did not. For participation in each additional indoor nonschool
      structured activity class, lesson, and program, BMI increased at a rate 0.05
      unit/year slower, and the attained BMI level at age 10 years was 0.48 units
      lower. CONCLUSION: Engagement in organized sports and activity programs as early
      as kindergarten and the first grade may result in smaller increases in BMI during
      the adiposity rebound period of childhood.

PMID- 22869404
TI  - Cranial computed tomography use among children with minor blunt head trauma:
      association with race/ethnicity.
AB  - OBJECTIVE: To determine if patient race/ethnicity is independently associated
      with cranial computed tomography (CT) use among children with minor blunt head
      trauma. DESIGN: Secondary analysis of a prospective cohort study. SETTING:
      Pediatric research network of 25 North American emergency departments. PATIENTS:
      In total, 42 412 children younger than 18 years were seen within 24 hours of
      minor blunt head trauma. Of these, 39 717 were of documented white non-Hispanic,
      black non-Hispanic, or Hispanic race/ethnicity. Using a previously validated
      clinical prediction rule, we classified each child's risk for clinically
      important traumatic brain injury to describe injury severity. Because no
      meaningful differences in cranial CT rates were observed between children of
      black non-Hispanic race/ethnicity vs Hispanic race/ethnicity, we combined these 2
      groups. MAIN OUTCOME MEASURE: Cranial CT use in the emergency department,
      stratified by race/ethnicity. RESULTS: In total, 13 793 children (34.7%)
      underwent cranial CT. The odds of undergoing cranial CT among children with minor
      blunt head trauma who were at higher risk for clinically important traumatic
      brain injury did not differ by race/ethnicity. In adjusted analyses, children of
      black non-Hispanic or Hispanic race/ethnicity had lower odds of undergoing
      cranial CT among those who were at intermediate risk (odds ratio, 0.86; 95% CI,
      0.78-0.96) or lowest risk (odds ratio, 0.72; 95% CI, 0.65-0.80) for clinically
      important traumatic brain injury. Regardless of risk for clinically important
      traumatic brain injury, parental anxiety and request was commonly cited by
      physicians as an important influence for ordering cranial CT in children of white
      non-Hispanic race/ethnicity. CONCLUSIONS: Disparities may arise from the overuse
      of cranial CT among patients of nonminority races/ethnicities. Further studies
      should focus on explaining how medically irrelevant factors, such as patient
      race/ethnicity, can affect physician decision making, resulting in exposure of
      children to unnecessary health care risks.

PMID- 22869406
TI  - The parenting responsibility and emotional preparedness (PREP) screening tool: a
      3-item screen that identifies teen mothers at high risk for nonoptimal parenting.
AB  - OBJECTIVE To test the ability of a 3-item screening tool (Parenting
      Responsibility and Emotional Preparedness [PREP]) to detect adolescent mothers at
      elevated risk for nonoptimal parenting and poor child development outcomes at 2
      years of age. DESIGN A 4-site prospective cohort study conducted from December
      2001 to August 2007 of adolescent mothers recruited in the third trimester of
      pregnancy and followed up at 4, 8, 18, and 24 months post partum. SETTING
      Community clinics and home settings in Birmingham, Alabama; Kansas City, Kansas
      and Missouri; South Bend, Indiana; and Washington, DC. PARTICIPANTS A total of
      270 first-time adolescent mothers (aged 15-19 years) and their infants (birth to
      2 years of age). MAIN EXPOSURES Naturalistic observations of parent-child
      interactions and quality of home environment during the first 2 years of life.
      OUTCOME MEASURES Maternal mental health and cognitive indicators, positive mother
      child interactions, quality of home environment, child social-emotional
      development, and child cognitive development (Bayley scales). RESULTS PREP scores
      identified adolescent mothers with significantly elevated depressive symptoms and
      childhood trauma and lower scores of knowledge of infant development and maternal
      IQ. PREP predicted significantly lower quality of home environments and higher
      levels of nonoptimal mother-child interactions at 4, 8, and 18 months. PREP also
      predicted significantly lower child outcomes at 2 years of age for cognitive
      scores and higher levels of depressive and withdrawal symptoms and dysregulation
      and negative emotionality. CONCLUSIONS PREP is a low-cost, easily administered,
      nonstigmatizing screening tool that identifies adolescent mothers who self
      recognize that they need help to meet their infants' social, emotional, and
      cognitive needs.

PMID- 22869405
TI  - Validation and refinement of a prediction rule to identify children at low risk
      for acute appendicitis.
AB  - OBJECTIVE: To validate and refine a clinical prediction rule to identify which
      children with acute abdominal pain are at low risk for appendicitis (Low-Risk
      Appendicitis Rule). DESIGN: Prospective, multicenter, cross-sectional study.
      SETTING: Ten pediatric emergency departments. PARTICIPANTS: Children and
      adolescents aged 3 to 18 years who presented with suspected appendicitis from
      March 1, 2009, through April 30, 2010. MAIN OUTCOME MEASURES: The test
      performance of the Low-Risk Appendicitis Rule. RESULTS: Among 2625 patients
      enrolled, 1018 (38.8% [95% CI, 36.9%-40.7%]) had appendicitis. Validation of the
      rule resulted in a sensitivity of 95.5% (95% CI, 93.9%-96.7%), specificity of
      36.3% (33.9%-38.9%), and negative predictive value of 92.7% (90.1%-94.6%).
      Theoretical application would have identified 573 (24.0%) as being at low risk,
      misclassifying 42 patients (4.5% [95% CI, 3.4%-6.1%]) with appendicitis. We
      refined the prediction rule, resulting in a model that identified patients at low
      risk with (1) an absolute neutrophil count of 6.75 * 103/MUL or less and no
      maximal tenderness in the right lower quadrant or (2) an absolute neutrophil
      count of 6.75 * 103/MUL or less with maximal tenderness in the right lower
      quadrant but no abdominal pain with walking/jumping or coughing. This refined
      rule had a sensitivity of 98.1% (95% CI, 97.0%-98.9%), specificity of 23.7%
      (21.7%-25.9%), and negative predictive value of 95.3% (92.3%-97.0%). CONCLUSIONS:
      We have validated and refined a simple clinical prediction rule for pediatric
      appendicitis. For patients identified as being at low risk, clinicians should
      consider alternative strategies, such as observation or ultrasonographic
      examination, rather than proceeding to immediate computed tomographic imaging.

PMID- 22869407
TI  - Is there a "bright future" for another screening test in pediatrics?: comment on:
      "the parenting responsibility and emotional preparedness (PREP) screening tool".

PMID- 22869408
TI  - Adolescent bariatric surgery.
AB  - Pediatric obesity has increased from a relatively uncommon problem to one of the
      most important public health problems facing children today. Typical "adult"
      diseases, such as type 2 diabetes mellitus, hypertension, and dyslipidemia, have
      become increasingly prevalent in the pediatric population. The earlier
      presentation of these comorbidities will have a significant impact for the future
      because this population of children will require more medical resources at an
      earlier age and will have a significantly decreased life expectancy. The
      significant morbidity of obesity in the pediatric population has led to
      consideration of more aggressive treatment protocols for obesity in children,
      including the introduction of surgical management at an earlier age. Surgery for
      obesity in adolescents has particular risks and benefits that must be accounted
      for when considering this approach. The unique psychological and emotional needs
      of adolescent patients make the patient selection process and perioperative
      management substantially different from those of adult patients. Initial outcomes
      of bariatric surgery in adolescents are comparable to those seen in adults in the
      short term. However, the long-term effects of these procedures on the adolescent
      population are not known. This review discusses the epidemiology of pediatric
      obesity, the indications for operative therapy in adolescent patients, the common
      surgical procedures used for weight loss, the reported outcomes of these
      procedures, and the importance of multidisciplinary management for this unique
      patient population.

PMID- 22869409
TI  - Picture of the month-quiz case. Early congenital syphilis.

PMID- 22869411
TI  - Disparities in health care: lack of equity arising from overuse (and vice versa).

PMID- 22869412
TI  - Prevalence of human papillomavirus infection in young women receiving the first
      quadrivalent vaccine dose.

PMID- 22869413
TI  - Trends in competitive venue beverage availability: findings from US secondary
      schools.

PMID- 22869415
TI  - Adolescent bariatric surgery.

PMID- 22869416
TI  - Molecular response of the human diaphragm on different modes of mechanical
      ventilation.
AB  - BACKGROUND: The mechanical stress that the human diaphragm is exposed to during
      mechanical ventilation affects a variety of processes, including signal
      transduction, gene expression, and angiogenesis. OBJECTIVES: The study aim was to
      assess the change in the production of major angiogenic regulators [vascular
      endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and
      transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and
      after contraction/relaxation cycles during mechanical ventilation. METHODS: This
      observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2,
      and TGFB1 in surgical patients receiving general anesthesia with controlled
      mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV
      without muscle relaxation (group B, n = 10), and pressure support of spontaneous
      breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient
      at two time points: 30 min after the induction of anesthesia (t1) and 90 min
      after the first specimen collection (t2). RESULTS: No significant changes in the
      mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C
      between time points t1 and t2. In contrast, in group B, the mRNA levels of the
      above angiogenic factors were increased in time point t2 compared to t1, a
      finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1
      = 0.001). CONCLUSIONS: These findings suggest that the molecular response of the
      human diaphragm before and after application of diverse modes of mechanical
      ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and
      TGFB1 was only promoted in CMV without muscle relaxation, and this may have
      important clinical implications.

PMID- 22869417
TI  - Prognostic implication of thyroglobulin and quantified whole body scan after
      initial radioiodine therapy on early prediction of ablation and clinical response
      for the patients with differentiated thyroid cancer.
AB  - OBJECTIVE: To investigate predictors for successful ablation and disease-free
      status after high-dose radioiodine therapy in patients with differentiated
      thyroid cancer. METHODS: We enrolled 173 consecutive patients with differentiated
      thyroid cancer between November 2001 and December 2004 retrospectively (female
      145, 46 +/- 12 years). All patients underwent total thyroidectomy and I-131
      ablative therapy (IAT) (3.7-5.4 GBq). The success or failure of ablation was
      assessed 6-9 months after the IAT with reference to undetectable thyroglobulin
      (Tg) and negative I-131 whole body scan (WBS). Afterward, the decision for
      disease-free status was evaluated using Tg and WBS (follow-up period after 1st
      IAT 7-81 months, median 43 months, criteria of disease-free: less than 10 ng/ml
      TSH-stimulated Tg or less than 2 ng/ml TSH-unstimulated Tg and/or negative WBS).
      Clinical and tumoral factors such as sex, age, pathologic type, the size of
      tumor, quantified cervical uptake in WBS1, pattern in WBS1, ablative therapy
      dose, AJCC stage, lymph node (LN) stage, Tg just before IAT (Tg1), and ablation
      status were assessed using logistic regression analyses. RESULTS: There were 93
      successful ablations (54 %). Significant predictors for the ablation failure were
      Tg1 (OR = 8.42; 95 % CI = 2.76-25.69; p < 0.0001), LN metastasis (OR = 3.05; 95 %
      CI = 1.11-8.37; p = 0.031), and quantified cervical uptake in WBS1 (OR = 4.95; 95
      % CI = 1.07-22.88; p = 0.041). One hundred fifty-five patients were determined as
      disease-free after follow-up. All the eighteen patients with persistent disease
      were identified as ablation failure after first IAT. Significant predictors for
      the disease-free status were Tg1 (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.028),
      tumor size (OR = 0.53; 95 % CI = 0.28-0.96; p = 0.044), and quantified cervical
      uptake in WBS1 (OR = 0.87; 95 % CI = 0.76-0.98; p = 0.024). CONCLUSIONS: The
      thyroglobulin and quantified cervical uptake in whole body scan are significant
      predictors for the successful ablation and disease-free status after follow-up.

PMID- 22869418
TI  - Bioefficacy of novel cyanobacteria-amended formulations in suppressing damping
      off disease in tomato seedlings.
AB  - Biological control of plant pathogens is receiving increasing relevance, as
      compared to chemical methods, as they are eco-friendly, economical and indirectly
      improve plant quality and yield attributes. An investigation was undertaken to
      evaluate the potential of antagonistic cyanobacteria (Anabaena variabilis RPAN59
      and A. oscillarioides RPAN69) fortified formulations for suppressing damping off
      disease in tomato seedlings challenged by the inoculation of a fungal consortium
      (Pythium debaryanum, Fusarium oxysporum lycopersici, Fusarium moniliforme and
      Rhizoctonia solani). Treatment with A. variabilis amended formulations recorded
      significantly higher plant growth parameters, than other treatments, including
      biological control (Trichoderma formulation) and chemical control (Thiram
      Carbendazim). The A. variabilis amended compost-vermiculite and compost
      formulations exhibited 10-15 % lower disease severity and 40-50 % higher values
      than chemical and biological control treatments in terms of fresh weight and
      height of the plants. In future, in depth analyses regarding the mechanism
      involved in biocontrol by cyanobacteria and evaluation of these formulations
      under field conditions are proposed to be undertaken.

PMID- 22869449
TI  - Vertebral body stenting / stentoplasty.
AB  - Osteoporotic vertebral fractures are frequent. Although the majority of fractures
      follow a benign course, there are certain fracture types which result in severe
      spinal deformity and / or are associated with neurological complications. These
      patients should be detected early and undergo surgical treatment. Vertebroplasty
      remains an important and effective treatment option for acute painful vertebral
      fractures showing progressive collapse. By this procedure the fracture can be
      stabilised, the pain is controlled and the progression of height loss is also
      halted. If a vertebral body shows a higher degree of collapse and kyphotic
      deformity or even some posterior wall involvement, the stentoplasty procedure
      (further evolution of kyphoplasty) allows height resotartion by the stent and the
      stabilisation of the vertebral body by cement.

PMID- 22869450
TI  - Prevalence of HPV infection and genotype distribution in women from Africa
      seeking asylum in Puglia, Italy.
AB  - HPV type-specific distribution was evaluated in genital samples collected from
      151 women from West Africa and Horn of Africa, living in the Asylum Seeker Center
      in Bari Palese (Italy), undergoing voluntary screening correlated with
      cytological abnormalities. HPV-DNA was assayed by Linear Array HPV genotyping
      test. HPV DNA was detected in 39.1 % of the women, 42.5 % of which had multiple
      infection and 69.5 % had high-risk HPV infection. Age-prevalence rates evidenced
      a peak of HPV infection in women <= 20 years of age (53.1 %). HPV 53 and 16 were
      the most common viral types (13.5 and 12.0 % respectively). Abnormal Pap test
      results were found in 4.4 % of women with known cytological result. Although a
      prevalence of HPV positive women higher in African than in European women was
      expected, the differing rate between residents and migrants African women must be
      investigated in future studies.

PMID- 22869451
TI  - Can propranalol prevent hepatocellular carcinoma?
AB  - beta-Adrenergic signaling is involved in many processes that may contribute to
      cancer progression. In this issue of the journal (beginning on page 1007),
      Nkontchou and colleagues report their retrospective observational finding that
      the beta-blocker propranolol was associated with a highly statistically
      significant reduction in the incidence of hepatocellular carcinoma in patients
      with advanced cirrhosis and related esophageal varices. This surprising finding
      requires confirmation, but the result is biologically plausible. Epidemiologic
      studies have linked beta-blockers with reduced rates of metastasis of other
      cancers and reduced cancer mortality. Laboratory studies suggest biologic
      mechanisms for anticancer effects of beta-blockers.

PMID- 22869452
TI  - Multidrug-resistant tuberculosis in an adult with cystic fibrosis.
AB  - Mycobacterium tuberculosis infection in patients with cystic fibrosis (CF) is
      rare. We report a 22-year-old CF patient with high fever, dyspnea and weight loss
      that progressively worsened over 2 weeks before admission. The patient suffered
      from liver cirrhosis, was colonized with Pseudomonas aeruginosa and had been
      repeatedly hospitalized for pulmonary infections. The patient was treated
      initially as for an exacerbation of P. aeruginosa infection, but tuberculosis
      (TBC) was suspected due to lack of improvement. A CT of the chest revealed
      enlarged bilateral cavities in the upper and middle lobes. A tuberculin skin test
      was positive, and M. tuberculosis nucleic acid was isolated from sputum samples.
      After receiving first-line anti-TBC drugs for 1 month, the patient's condition
      continued to worsen so molecular drug susceptibility testing was performed.
      Multidrug-resistant TBC was discovered, leading to a change in regimen. The
      patient was treated with ethionamide, moxifloxacin, linezolid, amikacin,
      imipenem/cilastatin and rifabutin and showed a remarkable clinical improvement.
      Although nontuberculous mycobacteria are more common in CF, the possibility of
      TBC should not be ignored. In that setting, early suspicion of infection due to
      resistant M. tuberculosis can be life saving.

PMID- 22869453
TI  - Non-invasive ventilation for severe TRALI and myocardial stunning: report and
      literature review.
AB  - Transfusion-related acute lung injury (TRALI) is a frequently under-diagnosed,
      although potentially fatal, condition that represents a leading cause of
      transfusion-related morbidity and mortality even in pediatric patients. Its main
      clinical features are characterized by rapidly evolving respiratory distress,
      hypoxia, pulmonary edema, and bilateral infiltrates on chest radiograph during or
      within 6 h of transfusion. We present a case of severe TRALI associated with
      myocardial stunning that occurred in a 14-year-old girl, and review the existing
      literature of pediatric TRALI. Our report suggests a potential role for NIV in
      the management of TRALI as the best profile both in terms of safety and
      effectiveness for hematologic patients.

PMID- 22869455
TI  - The work role functioning questionnaire 2.0 (Dutch version): examination of its
      reliability, validity and responsiveness in the general working population.
AB  - PURPOSE: The promotion of a sustainable, healthy and productive working life
      attracts more and more attention. Recently the Work Role Functioning
      Questionnaire (WRFQ) has been cross-culturally translated and adapted to Dutch.
      This questionnaire aims to measure the health-related work functioning of workers
      with health problems. The aim of this study is to evaluate the reliability,
      validity (including five new items) and responsiveness of the WRFQ 2.0 in the
      working population. METHODS: A longitudinal study was conducted among workers.
      The reliability (internal consistency, test-retest reliability, measurement
      error), validity (structural validity-factor analysis, construct validity by
      means of hypotheses testing) and responsiveness of the WRFQ 2.0 were evaluated.
      RESULTS: A total of N = 553 workers completed the survey. The final WRFQ 2.0 has
      four subscales and showed very good internal consistency, moderate test-retest
      reliability, good construct validity and moderate responsiveness in the working
      population. The WRFQ was able to distinguish between groups with different levels
      of mental health, physical health, fatigue and need for recovery. A moderate
      correlation was found between WRFQ and related constructs respectively work
      ability and work productivity. A weak relationship was found with general self
      rated health, work engagement and work involvement. CONCLUSION: The WRFQ 2.0 is a
      reliable and valid instrument to measure health-related work functioning in the
      working population. Further validation in larger samples is recommended,
      especially for test-retest reliability, responsiveness and the questionnaire's
      ability to predict the future course of health-related work functioning.

PMID- 22869456
TI  - Determinants of physical therapy use by compensated workers with musculoskeletal
      disorders.
AB  - PURPOSE: The study aim was to quantify physiotherapy service distribution among
      compensated workers with musculoskeletal disorders, and identify risk factors for
      under- and overuse. Andersen and Newman's model of service use determinants was
      adapted for a compensated population, to provide a conceptual basis for the
      analyses. METHODS: WorkSafe Victoria (Australia) workers' compensation claims
      were analysed retrospectively. Workers with musculoskeletal disorders resulting
      in at least 10 days off work were included if their claim commenced between 1-1
      2001 and 1-1-2005 (n = 36,995). Physiotherapy use over 4 years of follow-up was
      determined from service payment data. Regression models were used relating
      individual level predictors, regional physiotherapist supply and the role of
      individual physiotherapists to service use. RESULTS: Physiotherapy was used by
      26,026 (70 %) workers. Young age, male gender, working as a labourer, disorders
      of the joints, and not being hospitalised were associated with non-use. Use above
      the 90th percentile (>125 sessions over 4 years) was considered 'high use': high
      users accounted for 41 % of all use. Age 50-60, female gender, working as
      tradespersons, and substantial hospital costs were associated with high use. For
      workers living in the most disadvantaged areas, use was positively associated
      with supply. Negative binomial modelling of the role of physiotherapists
      indicated that service providers were associated with the number of sessions
      used. CONCLUSIONS: Physiotherapy services were not underused, but a small group
      of patients had very high use. Recommendations to limit overuse should be aimed
      at physiotherapists, and these could include effective monitoring of adherence to
      proposed treatment plans.

PMID- 22869457
TI  - Coronary telangiectasia associated with hypertrophic cardiomyopathy.
AB  - AIMS: Coronary telangiectasia (CT) is a rare congenital anomaly causing
      ventricular shunt and myocardial ischaemia. Its prevalence, genetic background,
      and impact in human hypertrophic cardiomyopathy (HCM) are unknown and were
      therefore investigated in this study. METHODS AND RESULTS: Among 445 patients
      with HCM, 195 had a coronary angiography and 124 a left ventricular
      endomyocardial biopsy. CT draining into the ventricular cavities was observed in
      5 of 195 HCM patients (2.5%), whereas it was detected in 0.1% of 1000 consecutive
      subjects without congenital anomalies undergoing coronary angiography. Patients
      with CT-HCM underwent a total body computed tomography scan to investigate the
      presence of systemic vascular malformations. HCM-related MYH7, MYBPC3, TNNT2, and
      TPM1 genes and hereditary haemorragic telangiectasia-related endoglin and activin
      receptor-like kinase 1 genes were analysed. Histology, clinical profile, and
      outcome of CT-HCM patients were correlated with those of 22 control HCM patients.
      No mucocutaneous or systemic vascular malformations were detected. Gene analysis
      showed a MYH7 mutation in two patients, with an associated endoglin point
      mutation. Histology showed in the CT-HCM cohort a more pronounced myocardial
      fibrosis (29.8 +/- 3.8%) compared with HCM controls (13 +/- 2.6%), and
      disorganized cardiomyocytes separated by thin-walled large vessels adherent to
      the endocardium. Clinically, the CT-HCM cohort had a higher arrhythmic profile at
      diagnosis and increased incidence of implantable cardioverter defibrillator (ICD)
      implantations and arrhythmic deaths during a long-term follow-up. CONCLUSION: CT
      is detectable in 2.5% of HCM patients vs. 0.1% of the general population; it may
      derive from a co-existing endoglin gene mutation and cause a prominent,
      potentially arrhythmogenic myocardial fibrosis.

PMID- 22869458
TI  - Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N
      terminal pro brain natriuretic peptide in heart failure with preserved vs.
      reduced ejection fraction.
AB  - AIMS: Growth differentiation factor 15 (GDF15), ST2, high-sensitivity troponin T
      (hsTnT), and N-terminal pro brain natriuretic peptide (NT-proBNP) are biomarkers
      of distinct mechanisms that may contribute to the pathophysiology of heart
      failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis
      (hsTnT); and wall stress (NT-proBNP)]. METHODS AND RESULTS: We compared
      circulating levels of GDF15, ST2, hsTnT, and NT-proBNP, as well as their
      combinations, in compensated patients with clinical HF with reduced ejection
      fraction (HFREF) (n = 51), HF with preserved ejection fraction (HFPEF) (n= 50),
      and community-based controls (n = 50). Compared with controls, patients with
      HFPEF and HFREF had higher median levels of GDF15 (540 pg/mL vs. 2529 and 2672
      pg/mL, respectively), hsTnT (3.7 pg/mL vs. 23.7 and 35.6 pg/mL), and NT-proBNP
      (69 pg/mL vs. 942 and 2562 pg/mL), but not ST2 (27.6 ng/mL vs. 31.5 and 35.3
      ng/mL), adjusting for clinical covariates. In receiver operating characteristic
      curve analyses, NT-proBNP distinguished HFREF from controls with an area under
      the curve (AUC) of 0.987 (P < 0.001); GDF15 distinguished HFPEF from controls
      with an AUC of 0.936 (P < 0.001); and the combination of NT-proBNP and GDF15
      distinguished HFPEF from controls with an AUC of 0.956 (P < 0.001). NT-proBNP and
      hsTnT levels were higher in HFREF than in HFPEF (adjusted P < 0.04). The NT
      proBNP:GDF15 ratio distinguished between HFPEF and HFREF with the largest AUC
      (0.709; P < 0.001). CONCLUSIONS: Our study provides comparative data on
      physiologically distinct circulating biomarkers in HFPEF, HFREF, and controls
      from the same community. These data suggest a prominent role for myocardial
      injury (hsTnT) with increased wall stress (NT-proBNP) in HFREF, and systemic
      inflammation (GDF15) in HFPEF.

PMID- 22869459
TI  - Plasma endothelin-1 and vascular endothelial growth factor levels and their
      relationship to hemodynamics in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Pulmonary hypertension (PH) is associated with a poor prognosis in
      idiopathic pulmonary fibrosis (IPF). Endothelin-1 (ET-1) and vascular endothelial
      growth factor (VEGF) are important in both fibrosis and vascular remodeling.
      OBJECTIVES: We sought to determine the relationship between ET-1 and VEGF levels
      and hemodynamics in patients with IPF. We hypothesized that higher levels of ET-1
      and VEGF would be associated with higher pulmonary artery pressures (PAP) and
      pulmonary vascular resistance (PVR) in patients with IPF. METHODS: We performed a
      cross-sectional analysis of 52 adults with IPF enrolled in a prospective cohort
      with available clinical data, platelet-free plasma, and hemodynamics. ET-1 and
      VEGF levels were measured via immunoassay. The associations of ET-1 and VEGF with
      PAP and PVR were examined using generalized additive models adjusted for age,
      gender, race/ethnicity, and forced vital capacity (% predicted). RESULTS: Sixteen
      of 52 (30.8%) had PH (mean PAP >=25 mm Hg). After multivariable adjustment,
      higher ET-1 levels were significantly associated with higher systolic (p = 0.01),
      diastolic (p = 0.02), and mean (p = 0.01) PAP and possibly higher PVR (p = 0.09).
      There were no significant associations between VEGF levels and hemodynamics.
      CONCLUSIONS: Higher levels of ET-1 were associated with higher PAP and possibly
      higher PVR in participants with IPF. In a subgroup of patients, ET-1 may be a
      contributor to pulmonary vascular disease burden in IPF.

PMID- 22869460
TI  - Enduring as lived experience: exploring the essence of spiritual resilience for
      women in late life.
AB  - The purpose of this study was to explore spirituality and its relationship to
      resilience for women in late life. Over thirty interviews with six women aged 80
      and older provide a dataset allowing for the phenomenological investigation of
      spiritual resilience. Themes emerged illustrating the components of spiritual
      resilience. The components of spiritual resilience are having divine support,
      maintaining purpose, and expressing gratitude. These factors are essential to the
      women's resilience and act as mechanisms that promote high levels of subjective
      well-being and an overall good quality of life. Essentially, participants
      articulate how their experiences of enduring hardships are informed by spiritual
      resilience. 

PMID- 22869461
TI  - Urchinlike nanostructure of single-crystalline nanorods of Sb2S3 formed at mild
      reaction condition.
AB  - Urchinlike nanostructure of well-defined Sb(2)S(3) crystals of 3-4 MUm in length
      and 30-150 nm in diameter oriented along [001] direction have been produced at a
      mild reaction temperature of 90  degrees C from SbCl(3) and S-methyl 3
      phenyldithiocarbazate [C(6)H(5)NHNHC(S)SMe] in ethylene glycol medium. During the
      reaction, the amorphous Sb(2)S(3) spheres of 1.4 MUm in diameter were formed at
      early reaction stage and then crystalline nanorods were continuously grown at the
      surface of Sb(2)S(3) spheres while transforming their morphology into urchinlike
      structure. The urchinlike Sb(2)S(3) was composed of single-crystalline Sb(2)S(3)
      nanorods, belong to the orthorhombic phase with cell parameters a = 11.307 A, b =
      11.278 A, c = 3.847 A and absorbed the light up to 750 nm-wavelength region. The
      urchinlike Sb(2)S(3) architecture was applied to the photoelectrochemical cell.

PMID- 22869462
TI  - Updated reference ranges for the ductus venosus pulsatility index at 11-13 weeks.
AB  - OBJECTIVE: To update the reference ranges for the ductus venosus pulsatility
      index (DVPI) at 11+0 to 13+6 gestational weeks. METHODS: DVPI was calculated in
      14,444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine Centers,
      during a 4-year period. Using previously described medians, DVPI evolution was
      assessed both over the study period on a yearly basis and over gestation,
      grouping fetuses according to 5-mm crown-rump length (CRL) ranges. Weighted DVPI
      medians, the 5th and 95th percentiles and distribution parameters for unaffected
      and trisomy 21 fetuses were newly calculated. RESULTS: A significant DVPI
      multiple of the median decrease was observed over both the study period (p <
      0.01) and over gestation (p < 0.01) using previous medians, in the two centers.
      Newly calculated weighted medians were lower than those previously described,
      decreasing with CRL. Distribution parameters calculated using the new medians
      were different from those previously described. CONCLUSION: DVPI reference ranges
      were lower than those previously reported and decreased with CRL. Updated medians
      and distribution parameters should be considered to include the DVPI as a
      Gaussian marker in trisomy 21 screening and for quality control purposes.

PMID- 22869463
TI  - Electrophilic addition of chlorine monofluoride for PET tracers.
AB  - PURPOSE: We have studied the utility of [(18)F]ClF electrophilic addition to the
      carbon-carbon double bond of analogues of a model positron emission tomography
      (PET) tracer, [(18)F]EF5. The consequence of simultaneous chlorine/fluorine
      addition on lipophilicity and biological activity of the molecule is evaluated.
      PROCEDURES: Post-target produced [(18)F]F2 was reacted with Cl2 to produce
      [(18)F]ClF, which was used in electrophilic addition. RESULTS: [(18)F]ClF was
      produced and used to label chlorinated analogues of [(18)F]EF5. The chlorinated
      analogues, [(18)F]EF4Cla and [(18)F]EF4Clb, were synthesized simultaneously. The
      in vivo uptake of the analogues compared well with [(18)F]EF5 uptake in tumor
      bearing mice. CONCLUSION: [(18)F]ClF is a suitable labeling reagent for
      electrophilic addition to double bonds of PET tracers. The results show that the
      modification of the pentafluoro group of [(18)F]EF5 by monofluorine-for-chlorine
      exchange affected the lipophilicity, but the hypoxia avidity of these molecules
      was not apparently altered.

PMID- 22869464
TI  - Fibrinogen and altered hemostasis in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) plaques, tau
      tangles, brain atrophy, and vascular pathology. Vascular defects include
      cerebrovascular dysfunction, decreased cerebral blood flow, and blood brain
      barrier (BBB) disruption, among others. Here, we review the evidence that links
      Abeta with the vascular pathology present in AD, with a specific focus on the
      hemostatic system and the clotting protein fibrinogen. Fibrinogen is normally
      found circulating in blood, but in AD it deposits with Abeta in the brain
      parenchyma and cerebral blood vessels. We found that Abeta and fibrin(ogen)
      interact, and their binding leads to increased fibrinogen aggregation, Abeta
      fibrillization, and the formation of degradation-resistant fibrin clots.
      Decreasing fibrinogen levels not only lessens cerebral amyloid angiopathy and BBB
      permeability, but it also reduces microglial activation and improves cognitive
      performance in AD mouse models. Moreover, a prothrombotic state in AD is
      evidenced by increased clot formation, decreased fibrinolysis, and elevated
      levels of coagulation factors and activated platelets. Abnormal deposition and
      persistence of fibrin(ogen) in AD may result from Abeta-fibrin(ogen) binding and
      altered hemostasis and could thus contribute to Abeta deposition, decreased
      cerebral blood flow, exacerbated neuroinflammation, and eventual
      neurodegeneration. Blocking the interaction between fibrin(ogen) and Abeta may be
      a promising therapeutic target for AD.

PMID- 22869465
TI  - Association of lower hemoglobin level and neuropathology in community-dwelling
      older persons.
AB  - Lower hemoglobin levels have been associated with cognitive decline in older
      persons. The objective of this study was to investigate the relationship between
      lower hemoglobin levels and common, age-related neuropathologies associated with
      cognitive decline. Hemoglobin and neuropathology measures were available in 113
      deceased, community-dwelling, older adults participating in the Rush Memory and
      Aging Project, a prospective, observational, clinical pathology study of aging.
      The mean hemoglobin level was 13.0 g/dL (SD = 1.4) and was measured 3.2 (SD =
      1.3) years prior to death. Thirty-five participants had at least one chronic
      macroscopic infarction and twenty-nine had at least one chronic microscopic
      infarction. Eleven participants had Lewy Bodies. The mean Alzheimer's disease
      pathology score based on a summary measure of neuritic plaques, diffuse plaques,
      and neurofibrillary tangles was 0.56 unit (SD = 0.56; range = 0, 2.34). Using
      logistic regression models adjusted for age at death, gender, and education, each
      g/dL lower hemoglobin level increased the odds for having a chronic macroscopic
      infarction by 37% (95% CI = 1.01, 1.86) but not for having a chronic microscopic
      infarction (OR = 1.11; 95% CI = 0.82, 1.52) or Lewy Bodies (OR = 1.07; 95% CI =
      0.68, 1.68). In an adjusted multiple regression model, hemoglobin level was not
      associated with the global AD pathology measure (parameter estimate = -0.02, SE =
      0.03, p = 0.6). In secondary analyses, lower hemoglobin levels were associated
      with higher odds of having a chronic macroscopic infarction in a subcortical
      region but not with higher total subcortical chronic macroscopic infarction
      volume. In conclusion, lower hemoglobin levels appear to be associated with
      chronic macroscopic infarctions but not other common age-related
      neuropathologies.

PMID- 22869466
TI  - Hypertension is related to the microstructure of the corpus callosum: the RUN DMC
      study.
AB  - Vascular factors play a role in the etiology of Alzheimer's disease (AD),
      presumably due to emergence of white matter lesions. However, important white
      matter structures involved in the etiology of AD, including the corpus callosum
      (CC), remain invariably free from macroscopical white matter lesions, although
      loss of microstructural integrity assessed with diffusion tensor imaging (DTI)
      has been described in the CC. Vascular factors have been related to these
      microstructural white matter changes too, but little is known about their effect
      on the CC. In 499 subjects with cerebral small vessel disease, aged 50-85 years,
      we cross-sectionally investigated the relation between hypertension, hypertension
      treatment status, the microstructural integrity of the CC using DTI, and the
      attendant cognitive performance. Fractional anisotropy and mean diffusivity were
      calculated in four substructures of the CC (genu, anterior body, posterior body,
      and splenium). Differences between groups were calculated with analysis of
      variance, adjusted for age, gender, and cardiovascular risk factors. Compared
      with normotensive subjects, hypertensive subjects had a lower fractional
      anisotropy in the splenium and a significant higher mean diffusivity in both the
      anterior body and the splenium; this was most noticeable in treated uncontrolled
      hypertensive subjects. Furthermore we found that microstructural integrity of the
      CC was related to global cognition. Of this relation, 14 to 60% was explained by
      the mediating effect of small vessel disease elsewhere in the white matter. Our
      findings indicate that adequate blood pressure treatment might postpone these
      changes and the attendant cognitive dysfunction.

PMID- 22869467
TI  - Recognition of self-heat shock protein 60 by T cells from patients with atopic
      dermatitis.
AB  - Heat shock protein 60 (hsp60) is a highly conserved stress protein and target of
      self-reactive T cells in various inflammatory diseases. Not much is known about a
      possible role in atopic disease. As atopic diseases are considered to be the
      result of a disturbance in the balance between T helper cells type 2 and
      regulatory T cells, it is of interest to know whether hsp60 acts as a bystander
      antigen in atopic disease. Our aim was to investigate whether hsp60 is involved
      in the chronicity of inflammation of atopic dermatitis (AD). We studied the
      expression of hsp60 in skin tissue of adults with AD by immunohistochemistry.
      Peripheral blood mononuclear cells (PBMC) of children with AD were cultured with
      hsp60 and proliferative responses, cytokine secretion, surface markers, and
      functional assays were compared to responses of PBMC of healthy controls (HC).
      Hsp60 was detected more in lesional skin of AD patients compared to nonlesional
      skin. Furthermore, PBMC of children with AD proliferated more strongly in
      response to hsp60 compared to HC. hsp60-reactive T cells of atopic children
      produced high levels of IFNgamma and low levels of IL-10. In vitro activation
      with hsp60 leads to the induction of CD4(+)CD25(bright) T cells expressing FOXP3
      in both HC as well as in atopic children. However, despite their regulatory
      phenotype, hsp60-induced CD4(+)CD25(bright)CD127(-)FOXP3(+) T cells of AD
      patients were incapable of suppressing effector T cells in vitro. hsp60 is
      recognized by proinflammatory (IFNgamma high, IL-10 low) T cells in atopic
      patients and is more present in lesional AD skin. This suggests that hsp60
      specific T cell responses contribute to local inflammation in AD.

PMID- 22869468
TI  - Hepatitis B precore protein: pathogenic potential and therapeutic promise.
AB  - Hepatitis B virus (HBV), a small and economically packaged double-stranded DNA
      virus, represents an enormous global health care burden. In spite of an effective
      vaccine, HBV is endemic in many countries. Chronic hepatitis B (CHB) results in
      the development of significant clinical outcomes such as liver disease and
      hepatocellular carcinoma (HCC), which are associated with high mortality rates.
      HBV is a non-cytopathic virus, with the host's immune response responsible for
      the associated liver damage. Indeed, HBV appears to be a master of manipulating
      and modulating the immune response to achieve persistent and chronic infection.
      The HBV precore protein or hepatitis B e antigen (HBeAg) is a key viral protein
      involved in these processes, for instance though the down-regulation of the
      innate immune response. The development of new therapies that target viral
      proteins, such as HBeAg, which regulates of the immune system, may offer a new
      wave of potential therapeutics to circumvent progression to CHB and liver
      disease.

PMID- 22869469
TI  - N-linked glycosylation in the hemagglutinin of influenza A viruses.
AB  - Since the 1918 influenza A virus (IAV) pandemic, H1N1 viruses have circulated in
      human populations. The hemagglutinin (HA) of IAV determines viral antigenicity
      and often undergoes N-linked glycosylation (NLG) at several sites. Interestingly,
      structural analysis of the 1918 and 2009 H1N1 pandemic viruses revealed antigenic
      similarities attributable to the conserved epitopes and the NLG statuses of their
      HA proteins. NLG of the globular head of HA is known to modulate the
      antigenicity, fusion activity, virulence, receptor-binding specificity, and
      immune evasion of IAV. In addition, the HA of IAV often retains additional
      mutations. These supplemental mutations compensate for the attenuation of viral
      properties resulting from the introduced NLG. In human H1N1 viruses, the number
      and location of NLG sites has been regulated in accordance with the antigenic
      variability of the NLG-targeted antibody-binding site. The relationship between
      the NLG and the antigenic variance in HA appears to be stably controlled in the
      viral context.

PMID- 22869470
TI  - Ischemic stroke among the patients with end-stage renal disease who were
      undergoing maintenance dialysis.
AB  - PURPOSE: In spite of higher incidence of stroke in end-stage renal disease (ESRD)
      patients compared to general population, the risk factor for stroke which is
      specific to ESRD is not fully understood. The ESRD patients who develop stroke
      may have certain additional risk factors compared to ESRD patients without
      stroke. We used registered data of Hallym Stroke Registry to elucidate the
      factors which affect development of ischemic stroke among the dialysis patients.
      MATERIALS AND METHODS: We recruited patients with acute ischemic stroke in ESRD
      patients undergoing maintenance dialysis. Dialysis patients without stroke were
      selected as control group with age and gender matching. We compared the
      demographic features, stroke risk factors, and laboratory findings in ESRD
      patients with or without ischemic stroke. RESULTS: The total of 25 patients with
      ESRD developed ischemic stroke. Fifty ESRD patients without stroke were chosen as
      the control group. The mean age of acute ischemic stroke patients was 59.80+/
      9.94 and male gender was 48%. The most common ischemic stroke subtype was small
      vessel occlusion (n=12), followed by large artery atherosclerosis (n=7). The
      patients with stroke had more frequent history of hypertension and higher
      systolic/diastolic blood pressure at the time of admission than the ESRD patients
      without stroke. Total cholesterol and LDL-cholesterol levels were significantly
      lower in the stroke group. In multivariate analysis, LDL-cholesterol was found to
      be the only risk factor for ischemic stroke. CONCLUSION: The results of our study
      reveal that LDL-cholesterol is associated with greater risk for ischemic stroke
      in the patients on dialysis.

PMID- 22869471
TI  - The impact of primary spontaneous pneumothorax on multiphasic personal inventory
      test results in young South Korean males.
AB  - PURPOSE: Few reports have documented psychopathological abnormalities in patients
      with primary spontaneous pneumothorax (PSP). We analyzed the results of a
      multiphasic personal inventory test to investigate the psychopathologic impact of
      PSP in young Korean males. MATERIALS AND METHODS: The authors reviewed the
      results of a Korean military multiphasic personal inventory (KMPI) administered
      to military conscripts in South Korea. A total of 234 young males participated in
      this study. The normal volunteer group (n=175) comprised individuals who did not
      have any lung disease. The PSP group (n=59) included individuals with PSP. None
      of the examinees had any psychological problems. The KMPI results of both groups
      were compared. RESULTS: There were more abnormal responses in the PSP group
      (17.0%) than the normal volunteer group (9.1%, p=0.002). The anxiety scale and
      depression scale scores of the neurosis category were greater for the PSP group
      than the normal group (p=0.039 and 0.014, respectively). The personality disorder
      and paranoia scale scores of the psychopathy category were greater for the PSP
      group than the normal group (p=0.007 and 0.018, respectively). CONCLUSION: Young
      males with PSP may have greater tendencies to suffer from anxiety, depression,
      personality disorders, and paranoia compared to normal individuals. Clinicians
      should be advised to evaluate the psychopathological aspects of patients with
      PSP.

PMID- 22869472
TI  - Effects of 600 mg versus 300 mg loading dose of clopidogrel in Asian patients
      with ST-segment elevation myocardial infarction undergoing primary percutaneous
      coronary intervention: long-term follow-up study.
AB  - PURPOSE: The optimum loading dose of clopidogrel has not been established in
      Asian patients with ST-segment elevation myocardial infarction (STEMI) undergoing
      primary percutaneous coronary intervention (PCI). Our aim was to evaluate the
      impact of different clopidogrel loading doses on short- and long-term clinical
      outcomes in Asian STEMI patients undergoing primary PCI. MATERIALS AND METHODS:
      We studied 691 STEMI patients undergoing primary PCI, loaded with 600 mg (n=381)
      or 300 mg (n=310) of clopidogrel. The primary outcome was major adverse cardiac
      events (MACEs), defined as a composite of all-cause death, reinfarction, or
      target vessel revascularization (TVR). RESULTS: Baseline clinical and peri
      procedural characteristics were mostly comparable between the 600 mg and 300 mg
      groups. There were no differences in 1 month MACEs as well as all-cause death,
      reinfarction, TVR, and stent thrombosis between the two groups. After a median
      follow-up of 921 days, MACEs [adjusted hazard ratio (HR) for the 600 mg group
      1.79, 95% confidence interval (CI): 0.80-3.97, p=0.153], all-cause death
      (adjusted HR for the 600 mg group 0.97, 95% CI: 0.50-1.88, p=0.928), reinfarction
      (adjusted HR for the 600 mg group 1.03, 95% CI: 0.55-1.91, p=0.937), and TVR
      (adjusted HR for the 600 mg group 1.36, 95% CI: 0.68-2.69, p=0.388) did not
      differ between the two groups. These results were reliable even after analysis of
      propensity score-matched population, and were also constant among various
      subgroups. CONCLUSION: A 600 mg loading dose of clopidogrel did not result in
      better short- and long-term clinical outcomes in Asian STEMI patients undergoing
      primary PCI.

PMID- 22869473
TI  - Clinical experience with the Bentall procedure: 28 years.
AB  - PURPOSE: We retrospectively analyzed 28 years of experience with the Bentall
      procedure in patients with aortic valve, aortic root, and ascending aortic
      disease. MATERIALS AND METHODS: Between March 1982 and December 2010, a total of
      218 patients underwent the Bentall procedure using a composite valved conduit.
      The "inclusion technique" was used in 30 patients (13.8%), the "open-button
      technique" in 181 patients (83.0%), and the Cabrol technique in 7 patients
      (3.2%). RESULTS: The early mortality rate was 5.5% (12/218). The mean follow-up
      duration was 108.0+/-81.0 months (range: 1-329 months). Seven patients required
      re-operation, and 1 patient required stent graft insertion at the descending
      thoracic aorta for progression of aortic arch or descending thoracic aortic
      dissection or aneurysm after the first operation, and 5 of them had Marfan
      syndrome. Kaplan-Meier estimated survival rates at 1, 5, 10, 20, and 25 years
      were 90.4%, 82.7%, 77.6%, 65.3%, and 60.3%, respectively. Freedom from
      reoperation rates at 1, 5, 10, 20, and 25 years were 99.0%, 98.3%, 95.5%, 90.8%,
      and 90.8%, respectively. CONCLUSION: In our experience, the Bentall procedure
      provided optimal survival with improved functional status. The disease of the
      aorta may progress, especially in patients with Marfan syndrome. Therefore,
      careful follow-up with regular computed tomography angiograms should be performed
      in these patients.

PMID- 22869474
TI  - Impact of clinicopathologic factors on subclinical central lymph node metastasis
      in papillary thyroid microcarcinoma.
AB  - PURPOSE: We evaluated whether the clinicopathological factors of papillary
      thyroid microcarcinoma (PTMC), especially tumoe size, are associated with
      subcinical central lymph node metastasis. MATERIALS AND METHODS: A total of 160
      patients diagnosed with PTMC who underwent total thyroidectomy with bilateral
      central lymph node dissection were enrolled in this study. All patients were
      clinically lymph node negative PTMC. Patients were divided into 2 groups
      according to the size of tumor (<=5 mm vs. >5 mm). Clinicopathologic risk factors
      for subclinical central lymph node metastasis were analyzed. RESULTS: Subclinical
      central lymph node metastasis was detected in 61 (38.1%). Patients with tumors
      <=5 mm had a lower frequency of extrathyroidal extension, multifocality and
      subclinical central lymph node metastasis. On multivariate analysis, only male
      and tumor size >5 mm were independent predictors of subclinical central lymph
      node metastasis; age, multifocality, bilaterality, extrathyroidal extension,
      lymphvascular invasion and lymphocytic thyroiditis were not. CONCLUSION: In this
      study, male and tumor size >5 mm were two independent predictive factors for
      subclinical central lymph node metastasis in PTMC. These are easier factors to
      assess before surgery than other factors when planning the central lymph node
      dissection. However, further long-term follow-up studies are needed to confirm
      the prognostic significance of subclinical central lymph node metastasis in PTMC.

PMID- 22869475
TI  - Prognostic and predictive value of carcinoembryonic antigen and cytokeratin-19
      fragments levels in advanced non-small cell lung cancer patients treated with
      gefitinib or erlotinib.
AB  - PURPOSE: The prognostic and predictive value of pretreatment 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. MATERIALS AND METHODS: Pretreatment CEA and CYFRA 21-1
      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. RESULTS: Low CYFRA 21-1 levels (l-CYFRA) were
      significantly associated with a good performance status (ECOG PS 0-1). The
      overall response rate (RR) was 27.6%, and 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 had significantly longer PFS and overall
      survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good
      prognosis in patients with unknown EGFR mutation status or patients with squamous
      cell carcinoma (p=0.021 and p=0.015, 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.
      CONCLUSION: 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, especially in patients with unknown EGFR mutation status
      or patients with squamous cell carcinoma.

PMID- 22869476
TI  - Prognostic significance of perirenal infiltration in renal cell carcinoma (<7
      cm).
AB  - PURPOSE: Pathologic stage is the most accurate prognostic factor of renal cell
      carcinoma. We evaluated whether perirenal fat infiltration is a significant
      factor in tumors 7 cm or less in size. MATERIALS AND METHODS: We retrospectively
      reviewed the record of 164 cases of tumors 7 cm or less in size. We divided the
      patients into two groups according to the presence of perirenal fat infiltration
      (group A, pT1; group B, pT3a). We evaluated relationships, recurrence-free
      survival and disease-specific survival according to clinicopathologic parameters.
      Statistical differences were calculated by log-rank test. RESULTS: A total 131
      patients were included in group A, with a mean age of 55.8 years, average tumor
      size was 4.2 cm, and a mean follow-up period of 43 months. Group B included 33
      patients, with a mean age of 55.9 years, an average tumor size of 4.1 cm, and a
      mean follow-up period of 38 months. There was no significant difference in
      disease-specific survival; however, recurrence-free survival showed significantly
      different between two groups (group A: 95.5%, group B: 84.4%). CONCLUSION: In
      this study, perirenal fat infiltration proved to be an independent prognostic
      factor for predicting disease-free survival in patients with tumors of 7 cm or
      less in size. Therefore, as this study showed, the presence of perirenal fat
      infiltration requires stricter follow-up planning, even in small renal cell
      carcinoma.

PMID- 22869477
TI  - Prognostic factors and characteristics of pancreatic neuroendocrine tumors:
      single center experience.
AB  - PURPOSE: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors.
      For PNETs, the predictive factors for survival and prognosis are not well known.
      The purpose of our study was to evaluate the predictive factors for survival and
      disease progression in PNETs. MATERIALS AND METHODS: We retrospectively analyzed
      37 patients who were diagnosed with PNET at Severance Hospital between November
      2005 and March 2010. Prognostic factors for survival and disease progression were
      evaluated using the Kaplan-Meier method. RESULTS: The mean age of the patients
      was 50.0+/-15.0 years. Eight cases (21.6%) were described as functioning tumors
      and 29 cases (78.4%) as non-functioning tumors. In univariate analysis of
      clinical factors, patients with liver metastasis (p=0.002), without resection of
      primary tumors (p=0.002), or American Joint Committee on Cancer/Union for
      International Cancer Control (AJCC/UICC) stage III/IV (p=0.002) were more likely
      to demonstrate shorter overall survival (OS). Patients with bile duct or
      pancreatic duct invasion (p=0.031), sized-lesions larger than 20 mm (p=0.036),
      liver metastasis (p=0.020), distant metastasis (p=0.005), lymph node metastasis
      (p=0.009) or without resection of primary tumors (p=0.020) were more likely to
      demonstrate shorter progression-free survival (PFS). In multivariate analysis of
      clinical factors, bile duct or pancreatic duct invasion [p=0.010, hazard ratio
      (HR)=95.046] and tumor location (non-head of pancreas) (p=0.036, HR=7.381) were
      confirmed as independent factors for predicting shorter PFS. CONCLUSION: Patients
      with liver metastasis or without resection of primary tumors were more likely to
      demonstrate shorter OS. Patients with bile duct or pancreatic duct invasion or
      tumors located at body or tail of pancreas were more likely to demonstrate
      shorter PFS.

PMID- 22869479
TI  - Patient perception of natural orifice transluminal endoscopic surgery in an
      endoscopy screening program in Korea.
AB  - PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a new method
      of accessing intracavitary organs in order to minimize pain by avoiding incisions
      in the body wall. The aim of this study is to determine patients' acceptance of
      NOTES in Korea and to compare their views about laparoscopic surgery and NOTES
      for benign and malignant diseases. MATERIALS AND METHODS: The target number of
      total subjects was calculated to be 540. The subjects were classified into 18 sub
      groups based on age groups, gender, and history of prior surgery. The
      questionnaire elicited information about demographic characteristics, medical
      check-ups, diseases, endoscopic and surgical histories, marital status and
      childbirth, the acceptance of NOTES, and the preferred routes for NOTES. In
      addition, the subjects chose laparoscopic surgery or NOTES for a hypothetical
      cholecystectomy and rectal cancer surgery, and responded to questions regarding
      the acceptable complication rate of NOTES, the appropriate cost of NOTES, and the
      reason(s) why they did not select NOTES. RESULTS: 486 of 540 patients (90.0%) who
      agreed to participate in this study completed the questionnaire. NOTES was
      preferred by the following patients: elderly; a history of treatment due to a
      disease; having regular check-ups; and a history of an endoscopic procedure
      (p<0.05). The most preferred route for NOTES was the stomach (67.1%). Eighty-four
      percent of the patients choosing NOTES responded that the complication rate of
      the new surgical method should be the same or lower than laparoscopic surgery.
      Vague anxiety over a new surgical method was the most common reason why NOTES was
      not selected in benign and malignant diseases (64% and 73%), respectively.
      CONCLUSION: Patients appear to be interested in the potential benefits of NOTES
      and would embrace it if their concerns about safety are met. We believe that
      qualified surgical endoscopists can meet these safety concerns, and that NOTES
      development has the potential to flourish.

PMID- 22869478
TI  - Comparative study of laparoscopy-assisted versus open subtotal gastrectomy for
      pT2 gastric cancer.
AB  - PURPOSE: Laparoscopy-assisted distal gastrectomy (LADG) is a widely accepted
      surgery for early gastric cancer. However, its use in advanced gastric cancer has
      rarely been studied. The aim of this study is to investigate the feasibility and
      survival outcomes of LADG for pT2 gastric cancer. MATERIALS AND METHODS: Between
      January 2004 and December 2009, we evaluated 67 and 52 patients who underwent
      open distal gastrectomy (ODG) and LADG, respectively, with diagnosis of pT2
      gastric cancer. The clinicopathological characteristics, postoperative outcomes,
      and survival were retrospectively compared between the two groups. RESULTS: There
      were statistically significant differences in the proximal margin of the
      clinicopathological parameters. The operation time was significantly longer in
      LADG than in ODG (207.7 vs. 159.9 minutes). There were 6 (9.0%) and 5 (9.6%)
      complications in ODG and LADG, respectively. During follow-up periods, tumor
      recurrence occurred in 7 (10.4%) patients of the ODG and in 4 (7.7%) patients of
      the LADG group. The 5-year survival rate of ODG and LADG was 88.6% and 91.3%
      (p=0.613), respectively. In view of lymph node involvement, 5-year survival rates
      were 96.0% in ODG versus 97.0% in LADG for patients with negative nodal
      metastasis (p=0.968) and 80.9% in ODG versus 78.7% in LADG for those with
      positive nodal metastasis (p=0.868). CONCLUSION: Although prospective study is
      necessary to compare LADG with open gastrectomy for the treatment of advanced
      gastric cancer, laparoscopy-assisted distal gastrectomy might be considered as an
      alternative treatment for some pT2 gastric cancer.

PMID- 22869480
TI  - A direct inhibitory effect of botulinum toxin type A on antral circular muscle
      contractility of guinea pig.
AB  - PURPOSE: Recent studies suggest new mechanisms of Botulinum toxin (BoNT) other
      than inhibiting acetylcholine (ACh) release from nerve terminals. The aim of this
      study was to determine whether other mechanisms for BoNT exist, so that it
      directly inhibits smooth muscle contraction. MATERIALS AND METHODS: Guinea pig
      antral muscle strips were studied in vitro after 2 hours of exposure to Botulinum
      toxin type A (BoNT/A). Contractile responses to electric field stimulation (EFS),
      high K(+) (60 mM) and ACh (100 MUM) were evaluated 24 and 48 hours after antral
      intramuscular injection of BoNT/A or vehicle. RESULTS: BoNT/A inhibited muscular
      contraction caused by high K(+) and ACh. Contractile responses to low (1 and 4
      Hz) and high (8 and 20 Hz) frequency EFS of antral muscle strips 24 and 48 hours
      after antral intramuscular injection of BoNT/A were significantly inhibited.
      CONCLUSION: The ability of BoNT/A to directly inhibit antral muscular
      contractility suggests a new mechanism for the pharmacologic actions of BoNT
      direct inhibition of muscular contraction.

PMID- 22869481
TI  - Clinical outcomes of tigecycline in the treatment of multidrug-resistant
      Acinetobacter baumannii infection.
AB  - PURPOSE: Acinetobacter baumannii (A. baumannii) has emerged as a major cause of
      nosocomial pneumonia and sepsis in seriously ill patients. Multidrug-resistant A.
      baumannii (MDRAB) is increasing in frequency, and the management of it's
      infections is consequently difficult. Therefore, tigecycline is considered to be
      the drug of choice for MDRAB treatment. The aim of our study was to evaluate the
      microbiological eradication and clinical effectiveness of tigecycline against
      MDRAB in seriously ill patients, including patients with ventilator-associated
      pneumonia (VAP). MATERIALS AND METHODS: We conducted a retrospective study
      including patients with A. baumannii infections who were treated with tigecycline
      between April 1, 2009 and March 31, 2010. We treated 27 patients with tigecycline
      for MDRAB infections. RESULTS: The mean age of patients was 66.2 years, and 20
      (74.1%) patients were male. The median length of stay at hospital was 74.6 days.
      MDRAB was eradicated from the site of infection in 23 cases (85.2%), however,
      only 17 cases (63.0%) showed positive clinical responses. Overall, an in-hospital
      mortality rate of 51.9% was observed, and 4 cases of death were attributable to
      sepsis. The combination therapy showed better clinical and microbial success
      rates than the monotherapy without significant difference. CONCLUSION: We
      observed the relatively low clinical success rate although the microbial
      eradication rate was high, probably due to superinfections in VAP and bacteremia.
      We suggest that clinicians should limit tigecycline monotherapy for MDRAB
      infection in critically ill patients, until large controlled clinical trials
      should be conducted.

PMID- 22869482
TI  - Clinical manifestations of aural fullness.
AB  - PURPOSE: Even though aural fullness is ubiquitous among patients presenting to
      otolaryngology clinics, the association between aural fullness and disease
      development has not yet been clearly determined. MATERIALS AND METHODS: Our study
      was performed on outpatients from June 2006 to February 2010 whose major
      complaint was "ear fullness", "aural fullness", or "ear pressure". We assessed
      their demographic and clinical characteristics, including sex, associated
      diseases, symptoms, otoscopic findings, audiology test results, and final
      diagnoses. RESULTS: Among 432 patients, 165 (38.2%) were males and 267 (61.8%)
      were females, with mean ages of 42+/-19 years and 47+/-17 years, respectively.
      Tinnitus, hearing disturbance, autophony (p<0.01) as well as nasal obstruction
      and sore throat (p<0.05) showed a statistically significant correlation with
      aural fullness. Among patients who complained of hearing fullness, tests and
      measures such as impedance audiometry, speech reception threshold, and pure tone
      audiometry generated statistically significant results (p<0.05). Ear fullness was
      most frequently diagnosed as Eustachian tube dysfunction (28.9%), followed by
      otitis media with effusion (13.4%) and chronic otitis media (7.2%). However,
      13.4% of patients could not be definitively diagnosed. CONCLUSION: Among patients
      complaining of ear fullness, Eustachian tube dysfunction, otitis media with
      effusion, chronic otitis media were most commonly observed. Performance of
      otoscopy, nasal endoscopy, the Valsalva maneuver, and additional audiological
      tests is necessary to exclude other diseases.

PMID- 22869483
TI  - Analysis of clinical feature and management of laryngeal fracture: recent 22 case
      review.
AB  - PURPOSE: Laryngeal fracture is rare, but complications are frequent and severe.
      Controversy still exists in regards to its proper management. The aim of this
      study was to present the clinical findings and management of laryngeal fracture
      in Korea. MATERIALS AND METHODS: We analyzed the medical records of 22 patients
      with laryngeal fracture at a tertiary care trauma center from 2000 to 2010
      retrospectively. RESULTS: In total, 22 patients (19 men and 3 woman) presented
      with laryngeal fractures caused by blunt (n=13) or penetrating (n=9) injury. Pain
      (68.1%), odynophagia (68.1%), hoarseness (18.1%), hemoptysis (13.6%), and
      subcutaneous emphysema (9%) were the common presenting symptoms and noncomminuted
      fracture was common. High velocity blunt trauma (mostly traffic accidents)
      patients had more extensive injury and poor voice outcomes. Penetrating trauma
      patients due to physical assault or suicide attempt demonstrated more frequently
      injuries on the left side. CONCLUSION: In driver-caused traffic accidents, where
      injuries in a wide area within the larynx occurred, poor voice results were seen,
      and these injuries required aggressive treatment. When endotracheal intubation
      was performed at experienced emergency centers with fiberoptic laryngoscopes,
      airway management was safely achieved. In addition, if the fractured laryngeal
      framework was corrected at appropriate times, voice results were good.

PMID- 22869484
TI  - Therapeutic effects of carbogen inhalation and lipo-prostaglandin E1 in sudden
      hearing loss.
AB  - PURPOSE: Vascular disorders and viral infections are considered the main causes
      of sudden hearing loss (SHL), although its pathogenesis remain unclear.
      Treatments include carbogen inhalation and lipo-prostaglandin E1 (lipo-PGE1),
      both of which have circulation-enhancing effects. We investigated the
      effectiveness of carbogen inhalation and lipo-PGE1 in SHL. MATERIALS AND METHODS:
      This retrospective review included 202 patients with idiopathic SHL who visited
      our clinic within 14 days of symptom onset between January 2006 and June 2010.
      All patients received oral prednisolone for 10 days. Of the 202 patients, 44
      received no additional treatment, 106 received additional carbogen inhalation,
      and 52 received additional lipo-PGE1. Hearing improvement was measured using
      Siegel's criteria. RESULTS: Overall recovery rates were 67.9% in the carbogen
      group, 53.8% in the lipo-PGE1 group, and 52.3% in the steroid-only control group
      (p=0.097). Limited to type 1 and type 2 categories of Sigels's criteria, the
      carbogen group had a significantly higher recovery rate (53.8%) than the lipo
      PGE1 group (26.9%) and the steroid-only control group (38.6%) (p=0.005).
      CONCLUSION: Carbogen inhalation added to steroid was a more effective treatment
      than lipo-PGE1 added to steroid or steroid alone in patients with SHL.

PMID- 22869485
TI  - Subsequent hip fracture in osteoporotic hip fracture patients.
AB  - PURPOSE: A significant number of patients who have experienced previous surgical
      treatment for an osteoporotic hip fracture experience a subsequent hip fracture
      (SHF) on the opposite side. This study aims to analyze the risk factors and the
      correlation between osteoporosis and SHF on the opposite side in order to assess
      the usefulness of bisphosphonate treatment for the prevention of SHFs. MATERIALS
      AND METHODS: We included 517 patients treated from March 1997 to April 2009 in
      this study. The inclusion criteria included previous unilateral hip fracture,
      without osteoporotic treatment, and a T-score less than -3.0 at the time of the
      fracture. We studied these patients in terms of death, SHF, alcoholism, living
      alone, dementia, dizziness, health status, osteoporotic treatment after fracture
      and bone mineral density (BMD). In total, 34 patients experienced a SHF. We
      selected another 34 patients without a SHF who had similar age, sex, body mass
      index, BMD, diagnosis, treatment and a follow up period for a matched pair study.
      We compared these two groups. The average follow up was 8.3 years and 8.1 years,
      respectively. RESULTS: The mortality rate of the 517 patients was 138 (27%). The
      BMD at the time of fracture demonstrated no statistical difference between the
      two groups (p>0.05). Nine patients (26%) within the SHF group were prescribed
      Risedronate and 18 patients (53%) received the same treatment in the non-SHF
      group. There was a statistical relationship with the treatment of osteoporosis
      (p=0.026). The average BMD of patients with SHF was -5.13 and -5.02 in patients
      without SHF was (p>0.05). CONCLUSION: Although primary surgical treatments are
      important for an excellent outcome in osteoporotic hip fractures, treatment of
      osteoporosis itself is just as important for preventing SHFs.

PMID- 22869486
TI  - Postoperative nausea and vomiting after myringoplasty under continuous sedation
      using midazolam with or without remifentanil.
AB  - PURPOSE: This prospective study evaluated the effects of continuous sedation
      using midazolam, with or without remifentanil, on postoperative nausea and
      vomiting (PONV) in patients undergoing myringoplasty. MATERIALS AND METHODS:
      Sixty patients undergoing myringoplasty were sedated with midazolam in the
      presence of remifentanil (group MR), or after saline injection instead of
      remifentanil (group M). RESULTS: Three patients (10%) in group M complained of
      nausea; two vomited. Four patients (13%) in group MR complained of nausea and
      vomited within 24 h after surgery. Rescue drugs were given to the six patients
      who vomited. No significant difference was detected between the two groups
      regarding the incidence or severity of nausea, incidence of vomiting, or need for
      rescue drugs. CONCLUSION: Midazolam-based continuous sedation can reduce PONV
      after myringoplasty. Compared with midazolam alone, midazolam with remifentanil
      produced no difference in the incidence or severity of nausea, incidence of
      vomiting, or need for rescue drugs.

PMID- 22869487
TI  - Remifentanil use in pediatric scoliosis surgery-an effective alternative to
      morphine (a retrospective study).
AB  - PURPOSE: The unique properties of remifentanil make it ideal for pediatric use
      despite a lack of wide randomized clinical trials and fear of adverse events due
      to its high potency. We aimed to consolidate preliminary conclusions regarding
      the efficacy of remifentanil use in pediatric scoliosis surgery. MATERIALS AND
      METHODS: The medical charts of children with idiopathic scoliosis who underwent
      primary spinal fusion between 1998 and 2007 at a large tertiary university
      affiliated hospital were retrospectively reviewed and divided into two groups
      according to anesthetic regime (remifentanil vs. morphine). Demographic, surgery
      related details and immediate postoperative course were recorded and compared.
      RESULTS: All 36 remifentanil children were extubated shortly after termination of
      surgery, compared to 2 of the 84 patients in the morphine group. The remaining
      patients in the morphine group were extubated hours after surgery [5.4 hours;
      standard deviation (SD) 1.7 hours]. Six remifentanil children were spared routine
      intensive care hospitalization (vs. 2 morphine children-significant difference).
      Shorter surgeries [5.6 hours (SD 1.82 hours) vs. 7.14 hours (SD 2.15 hours);
      p=0.0004] were logged for the remifentanil group. To achieve controlled
      hypotension during surgery, vasodilator agents were used in the morphine group
      only. A comparison of early postoperative major or minor complication rates
      (including neurological and pulmonary complications) between the two groups
      yielded no significant differences. CONCLUSION: Remifentanil use can shorten
      operating time and facilitate earlier spontaneous ventilation and extubation,
      with less of a need for intensive care hospitalization and no increase in
      significant complications.

PMID- 22869488
TI  - Spontaneous reporting of adverse drug reactions through electronic submission
      from regional society healthcare professionals in Korea.
AB  - PURPOSE: Pharmacovigilance Research Network built a spontaneous reporting system
      and collected adverse drug reactions (ADRs) by electronic submission (e-sub) in
      Korea. We analyzed ADRs spontaneously reported through e-sub from regional health
      professionals. MATERIALS AND METHODS: Nine hundred and thirty three ADR cases
      were collected and analyzed from January to December in 2008. "A matter" was
      defined as one symptom matched to one culprit drug included in an ADR case. We
      collected and analyzed e-sub ADR cases and matters to determine common culprits
      and organ specified ADR matters. RESULTS: There were 3,049 matters in 933 ADR
      cases for 1 year, and 3.3 matters per case were reported. In organ specific ADR
      classification, skin reactions which took the first place in 866 matters (28%)
      included urticaria and rash. The next cases were neurologic symptom (624 matters,
      21%) and gastrointestinal symptom (581 matters, 19%). Doctor (53%) and pharmacist
      (31%) were the most important participants in e-sub spontaneous reporting system,
      and 3% of ADR cases were reported by patients or their guardians. WHO-Uppsala
      Monitoring Center causality assessment results showed certain 10.6%, probable
      37.7%, possible 41.7% and below unlikely 10.0%. Culprit drugs were antibiotics
      (23.4%), neurologic agents (14.7%) and non-steroidal anti-inflammatory drugs
      (9.4%). CONCLUSION: In our study, antibiotic was most common culprit drug, and
      skin manifestation was most common symptom in e-sub ADRs collected from regional
      healthcare practitioners in Korea.

PMID- 22869489
TI  - Development of the rectus abdominis and its sheath in the human fetus.
AB  - PURPOSE: Although the rectus abdominis and its sheath are well known structures,
      their development in the human fetus is poorly understood. MATERIALS AND METHODS:
      We examined rectus abdominis and sheath development in semiserial horizontal
      sections of 18 fetuses at 5-9 weeks of gestation. RESULTS: Rectus muscle
      differentiation was found to commence above the umbilicus at 6 weeks and extend
      inferiorly. Until closure of the anterior chest wall via fusion of the bilateral
      sternal anlagen (at 7 weeks), the anterior rectal sheath originated from the
      external oblique and developed towards the medial margin of the rectus abdominis
      at all levels, including the supracostal part. After formation of the anterior
      sheath, fascial laminae from the internal oblique and transversus abdominis
      contributed to formation of the posterior rectus sheath. However, the posterior
      sheath was absent along the supracostal part of the rectus abdominis, as the
      transversus muscle fibers reached the sternum or the midline area. Therefore, it
      appeared that resolution of the physiological umbilical hernia (8-9 weeks) as
      well as chest wall closure was not required for development of the rectus
      abdominis and its sheath. Conversely, in the inferior part of the two largest
      fetal specimens, after resolution of the hernia, the posterior sheath underwent
      secondary disappearance, possibly due to changes in mechanical stress.
      CONCLUSION: Upward extension of the rectus abdominis suddenly stopped at the
      margin of the inferiorly developing pectoralis major without facing the external
      intercostalis. The rectus thoracis, if present, might correspond to the
      pectoralis.

PMID- 22869490
TI  - Gene expression pattern of human chorion-derived mesenchymal stem cells during
      adipogenic differentiation.
AB  - PURPOSE: The aim of this study was to identify the adipocyte-specific gene
      expression patterns in chorion-derived mesenchymal stem cells during adipogenic
      differentiation. MATERIALS AND METHODS: Chorionic cells were isolated from the
      third trimester chorions from human placenta at birth and identified
      morphologically and by fluorescence-activated cell sorting analysis. After
      inducing adipogenic differentiation for 28 days, cells at days 3, 10, 21 and 28
      were analyzed by Oil red O staining and RNA extraction in order to assess the
      expression levels of adipocyte marker genes, including CCAAT-enhancer binding
      protein alpha (C/EBPalpha), peroxisome proliferator- activated receptor gamma
      (PPARgamma), fatty acid binding protein 4 (FABP4) and Glycerol-3-phosphate
      dehydrogenase (GPD2). Cells not induced for differentiation were compared with
      the induced cells as a control group. RESULTS: Chorion-derived cells showed the
      same pattern as fibroblasts, and expressed CD73, CD105, and CD166 antigens, but
      not CD45, CD34, and HLA-DR antigens. On day 3 after differentiation, cells began
      to stain positively upon Oil red O staining, and continuously increased in lipid
      granules for 4 weeks. The expression level of C/EBPalpha increased 4.6 fold on
      day 3 after induction, and continued to increase for 4 weeks. PPARgamma was
      expressed at a maximum of 2.9 fold on day 21. FABP4 and GPD2 were significantly
      expressed at 4.7- and 3.0-fold, respectively, on day 21, compared to controls,
      and further increased thereafter. CONCLUSION: Human chorion-derived mesenchymal
      stem cells exhibited the sequential expression pattern of adipocyte marker genes
      during differentiation, corresponding to adipogenesis.

PMID- 22869491
TI  - Serum amyloid A circulating levels and disease activity in patients with juvenile
      idiopathic arthritis.
AB  - The aim of our study was to evaluate the association between circulating levels
      of serum amyloid A protein (SAA) and disease activity in patients with juvenile
      idiopathic arthritis (JIA). Our study group included 41 JIA patients (9 male, 32
      female), classified according to the International League of Associations for
      Rheumatology (ILAR) criteria (5); 16 had polyarticular onset disease and 25 had
      oligoarticular onset disease. Among 25 patients with oligoarticular disease,
      three had extended oligoarthritis. Serum amyloid A (SAA), erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) were measured in both
      patients and 26 healthy controls. SAA levels were higher in JIA patients versus
      healthy controls (p<0.001). Significant positive correlations were found between
      SAA and the presence of active joints (rho=0.363, p<0.05), the number of active
      joints (rho=0.418, p<0.05), ESR (R=0.702, p<0.05) and CRP (R=0.827, p<0.05). No
      significant correlations between ESR and the presence of active joints
      (rho=0.221, p=0.225) or between ESR and the number of active joints (rho=0.118,
      p=0.520) were demonstrated in JIA patients. No significant correlations were
      obtained between CRP and the presence of active joints (rho=0.034, p=0.855) or
      between CRP and the number of active joints (rho=0.033, p=0.859). We discovered a
      significant increase in SAA levels in JIA patients, compared to controls, and a
      strong positive correlation between SAA level and JIA disease activity. We also
      discerned SAA to be a more sensitive laboratory marker than ESR and CRP for
      evaluating the presence and number of active joints. We suggest that SAA can be
      used as an additional indicator of disease activity in JIA.

PMID- 22869492
TI  - Two cases of Wernicke's encephalopathy in young age patients receiving allogeneic
      hematopoietic stem cell transplantation.
AB  - Wernicke's encephalopathy is an acute neurolopsychiatric syndrome caused by
      thiamine deficiency, and classically presents with the triad of opthalmopathy,
      ataxia and altered mentality. Both prolonged total parenteral nutrition and
      reduced oral intake can induce Wernicke's encephalopathy during hematopoietic
      stem cell transplantation (HSCT). Although early treatment is important for
      recovery from Wernicke's encephalopathy, the vague symptoms and characteristics
      hinder early diagnosis. Furthermore, Wernicke's encephalopathy is not infrequent
      and can develop at any age during HSCT. Herein, we present two young patients
      developing Wernicke's encephalopathy during HSCT.

PMID- 22869493
TI  - Lung transplantation for bronchiolitis obliterans after allogeneic hematopoietic
      stem cell transplantation.
AB  - Bronchiolitis obliterans (BO) is a late onset complication of allogeneic
      hematopoietic stem cell transplantation (HSCT), and treatment outcome is dismal
      if it does not respond to immunosuppressive therapy. A 21-year-old male diagnosed
      with acute myeloid leukemia received an allogeneic HSCT from human leukocyte
      antigen- identical sibling donor. Twenty one months after transplantation, he
      developed progressive dyspnea and was diagnosed BO. Despite standard
      immunosuppressive therapy, the patient rapidly progressed to respiratory failure
      and Novalung(r) interventional lung-assist membrane ventilator was applied in the
      intensive care unit. Three months after the diagnosis of BO, the patient
      underwent bilateral lung transplantation (LT) and was eventually able to wean
      from the ventilator and the Novalung(r). Since the LT, the patient has been under
      a strict rehabilitation program in order to overcome a severe lower extremity
      weakness and muscle atrophy. Histologic findings of the explanted lungs confirmed
      the diagnosis of BO. Nine months after the LT, the patient showed no signs of
      rejection or infectious complications, but still required rehabilitation
      treatment. This is the first LT performed in a patient with BO after allogeneic
      HSCT in Korea. LT can be an effective therapy in terms of survival for patients
      with respiratory failure secondary to development of BO following HSCT.

PMID- 22869494
TI  - [Active surveillance for renal cell carcinoma].
AB  - The incidence of renal cell carcinoma (RCC) and especially that of small RCCs is
      increasing. However, not all tumours are malignant and not all malignant tumours
      are RCCs. Although partial nephrectomy is the therapeutic standard of care, an
      increasing number of patients is being treated with cryoablation, radiofrequency
      ablation, or active surveillance. The latter options require a pretherapeutic
      tumour biopsy. Approximately 85% of all biopsies can distinguish benign from
      malignant tumours. In the case of a RCC, histological subtype and grading are
      correctly diagnosed in 85% and 65%, respectively. However, tumour growth and
      metastasis in patients undergoing active surveillance cannot be predicted. A
      later tumour growth is the main trigger to change to active therapy. In this
      paper the results of tumour biopsy and active surveillance of patients with a
      renal mass are presented.

PMID- 22869495
TI  - [The urethral anastomosis in orthotopic neobladder following robot-assisted
      radical cystectomy (RARC) at German-speaking centres].
AB  - INTRODUCTION: Following robot-assisted radical cystectomy (RARC) and
      extracorporeal reconstruction, robotic continuous suture techniques and those
      using open or robotically pre-positioned single sutures are used for the
      urethroneovesical anastomosis. METHODS: 62 German-speaking robotic centres were
      asked in an online questionnaire whether they carried out RARC. Following an
      affirmative answer further questions were put to the form of the neobladder and
      the technique of the urethrovesical anastomosis. RESULTS: 80% of the online
      questionnaires were answered. 44% (n=22) of these centres perform the RARC.
      According to the answers, given all of the centres but one perform an
      extracorporeal construction of the neobladder [Studer bladder 73% (n=16),
      Hautmann bladder 18% (n=4), others 9% (n=2)]. After reconstruction 36% (n=8) of
      the teams perform a completely open surgical anastomosis with pre-positioned
      sutures, 24% (n=5) close the anastomosis in a single knot technique using
      robotically pre-positioned sutures and 40% (n=9) use continuous sutures during
      the intracorporeal reconstruction or after re-docking the robot. CONCLUSION:
      According to this questionnaire to German-speaking centres the most common
      anastomotic technique following extracorporeal reconstruction, mostly a Studer
      bladder, is that of the pre-positioned single knot sutures. This offers the
      advantage that a re-docking of the robotic cart is unnecessary. In contrast,
      however, to robotically performed suturing, there must be enough space in the
      open procedure to surgically tie-off the sutures of the anastomosis.

PMID- 22869496
TI  - [Simultaneous robot-assisted laparoscopic cystectomy and laparoscopic
      nephrectomy: first experience on 3 patients with short-term follow-up].
AB  - BACKGROUND: The standard treatment for the muscle-invasive bladder cancer (MIBC)
      adheres to the open radical cystectomy (RC), although in the last few years the
      RC was established in some centres. The MIBC with simultaneous renal pathology
      (carcinoma, loss of function) can be a reason for an RC in combination with a
      nephrectomy. In the present paper we give a report about our first 3 patients in
      whom we combined the robotic RC with a laparoscopic nephrectomy as a minimally
      invasive treatment. PATIENTS AND METHODS: Between January and September 2010 3
      male patients (average age 66 years) with MIBC and an associated renal pathology
      (2*loss of function, 1*upper tract carcinoma) were treated by the simultaneous
      robot-assisted RC and laparoscopic nephrectomy at our hospital. Clinical and
      pathological criteria, surgical techniques and preoperative complications were
      recorded prospectively. Follow-up of the 3 patients continued for at least of 18
      months. RESULTS: In all 3 cases primarily the kidney was prepared in a
      transperitoneal-laparoscopic way and clipped by the vessel pedicle, then the
      robot-assisted RC followed and specimens were removed through a 10-cm median
      laparotomy. In all cases an ileum conduit was built extracorporally in using this
      way. The median OP time (including nephrectomy, connection of Da-Vinci, RC with
      extended lymph node dissection) amounted to 7 h (6.5-7.5 h) in total. The
      intraoperative blood loss was 330 mL on average. One of our patients showed a
      grade 2 complication following the Clavien-Dindo classification (1*grade 1,
      1*without perioperative complications). On average 32 (22-46) lymph nodes were
      taken out, whereby all patients showed a pN0 status. The pathological stagings of
      MIBC were pT3a, pT4a and pT4b. With one patient the cancer of the renal pelvis
      was limited to the lamina propria, with another patient an incidental prostate
      cancer was detected. All histopathological findings of the different cancers
      showed negative surgical margins. The median hospitalisation time was 17 (16-19)
      days. In an 18- to 26-month follow-up period all patients -remained without any
      further postoperative complications and -without a tumour relapse. CONCLUSION: In
      this paper we have described the surgical steps of a small series of simultaneous
      robot-assisted RC and laparoscopic nephrectomy as a minimally invasive treatment
      in case of a specific indication. As a result of our report, we show that this
      surgical technique is possible without essential perioperative morbidity and with
      satisfying oncological results. Long-term data of our patients and results of any
      further studies are crucial to evaluate the efficiency of this complex surgical
      method.

PMID- 22869497
TI  - [PSA progression under hormone therapy - of prognostic relevance?].
AB  - In clinical routine, the anti-hormone therapy for prostate cancer with drugs is
      monitored by regular control measurements of the PSA value. An increase in the
      PSA value is considered to be a first sign of progression and thus of failure of
      the therapy. In the case of hormone-sensitive prostate carcinoma this means that
      the first stage of castration resistance has been reached. The question as to the
      relationship between PSA progression and overall survival as the most important
      clinical endpoint has been evaluated retrospectively in 2 studies. Both were able
      to confirm the relationship. However, in a therapy comparison, e.g., in phase III
      studies, the PSA progression does not have a surrogate status since the currently
      available analyses do not allow the recognition of an unambiguous relationship
      between the therapeutic effect on PSA progression and overall survival.

PMID- 22869498
TI  - [Systemic therapy for metastatic renal cell carcinoma].
AB  - A better understanding of molecular biological mechanisms involved in the
      pathogenesis or, respectively, prognosis of renal cell carcinoma has recently led
      to a fundamental change in those therapeutic options that are especially
      effective after systemic disemination. In this context, cytokine-based
      therapeutic concepts have been replaced by the so-called targeted therapeutic
      agents that include, above all, tyrosine kinase (TK) and mTOR inhibitors. The
      present contribution is intended to reflect the current state of the art in the
      systemic therapy for renal cell carcinoma in first- and second-line use. In
      addition, the increasing relevance of sequential therapy under consideration of
      possible side effects is discussed.

PMID- 22869499
TI  - [Circumcision with frenulum-plasty].

PMID- 22869500
TI  - Emergency obstetric referral in rural Sierra Leone: what can motorbike ambulances
      contribute? A mixed-methods study.
AB  - Giving birth remains a dangerous endeavour for many of the world's women.
      Progress to improve this has been slow in sub-Saharan Africa. The second delay,
      where transport infrastructure is key in allowing a woman to reach care, has been
      a relatively neglected field of study. Six eRanger motorbike ambulances,
      specifically engineered for use on poor roads in resource-poor situations were
      provided in 2006 as part of an emergency referral system in rural Sierra Leone.
      The aim of this study was to evaluate the implementation of this referral system
      in terms of its use, acceptability and accessibility. Data were collected from
      usage records, and a series of semi-structured interviews and focus groups
      conducted to provide deeper understanding of the service. A total of 130 records
      of patients being transported to a health facility were found, 1/3 of which were
      for obstetric cases. The ambulance is being used regularly to transport patients
      to a health care facility. It is well known to the communities, is acceptable and
      accessible, and is valued by those it serves. District-wide traditional birth
      attendant training and the sensitisation activities provided a foundation for the
      introduction of the ambulance service, creating a high level of awareness of the
      service and its importance, particularly for women in labour. Motorbike
      ambulances are suited to remote areas and can function on poor roads inaccessible
      to other vehicles. 

PMID- 22869501
TI  - Evaluation of renal blood flow using multi-phase echo-planar magnetic resonance
      imaging and signal targeting with alternating radiofrequency (EPISTAR) in 3-T
      magnetic resonance imaging.
AB  - Most arterial spin labeling techniques apply the constant post-labeling delay
      time after the blood-labeling time point on the target artery. As the hemodynamic
      status cannot be estimated in each patient, quantitative values of the blood flow
      may not be accurate. To overcome this problem, we performed renal perfusion
      imaging of human kidneys using multi-phase echo-planar magnetic resonance imaging
      and signal targeting with an alternating radiofrequency (EPISTAR) sequence at 3-T
      magnetic resonance imaging. Multi-phase EPISTAR obtained 17 phases every 100 ms
      between 250 and 1850 ms from the arterial-labeling time point. The highest signal
      intensity image obtained using multi-phase images was applied to renal blood flow
      (RBF) calculations. In five healthy volunteers, the mean cortical RBF was 286.6
      +/- 48.7 mL/100 g/min. This value was not significantly different from those in
      four previous studies. This technique was more useful than previous studies, in
      that multi-phase images could confirm the hemodynamic status on RBF calculations.

PMID- 22869502
TI  - Sulfur deposition simulations over China, Japan, and Korea: a model
      intercomparison study for abating sulfur emission.
AB  - In response to increasing trends in sulfur deposition in Northeast Asia, three
      countries in the region (China, Japan, and Korea) agreed to devise abatement
      strategies. The concepts of critical loads and source-receptor (S-R)
      relationships provide guidance for formulating such strategies. Based on the Long
      range Transboundary Air Pollutants in Northeast Asia (LTP) project, this study
      analyzes sulfur deposition data in order to optimize acidic loads over the three
      countries. The three groups involved in this study carried out a full year (2002)
      of sulfur deposition modeling over the geographic region spanning the three
      countries, using three air quality models: MM5-CMAQ, MM5-RAQM, and RAMS-CADM,
      employed by Chinese, Japanese, and Korean modeling groups, respectively. Each
      model employed its own meteorological numerical model and model parameters. Only
      the emission rates for SO(2) and NO(x) obtained from the LTP project were the
      common parameter used in the three models. Three models revealed some bias from
      dry to wet deposition, particularly the latter because of the bias in annual
      precipitation. This finding points to the need for further sensitivity tests of
      the wet removal rates in association with underlying cloud-precipitation physics
      and parameterizations. Despite this bias, the annual total (dry plus wet) sulfur
      deposition predicted by the models were surprisingly very similar. The ensemble
      average annual total deposition was 7,203.6 +/- 370 kt S with a minimal mean
      fractional error (MFE) of 8.95 +/- 5.24 % and a pattern correlation (PC) of 0.89
      0.93 between the models. This exercise revealed that despite rather poor error
      scores in comparison with observations, these consistent total deposition values
      across the three models, based on LTP group's input data assumptions, suggest a
      plausible S-R relationship that can be applied to the next task of designing cost
      effective emission abatement strategies.

PMID- 22869503
TI  - Development and modeling of a flat plate serpentine reactor for photocatalytic
      degradation of 17-ethinylestradiol.
AB  - A flat plate serpentine reactor modified from ultraviolet disinfection pool in
      municipal wastewater treatment plants was developed for the removal of 17
      ethinylestradiol (EE2) for the first time. The photocatalytic degradation
      performance of EE2 was investigated in this serpentine reactor under different
      conditions such as inlet concentrations, loaded catalyst concentrations, incident
      radiations fluxes, and flow velocities. More than 98% of EE2 was removed under
      certain conditions within 120 min. An integrated model including a six-flux
      adsorption-scattering model and a modified flow diffusion model was established
      to investigate the effect of radiation field and flow velocities, respectively. A
      satisfactory agreement was observed between the model simulation and experimental
      results, showing a potential for design and scale-up of photocatalytic reactor
      for wastewater treatment.

PMID- 22869504
TI  - Using a source-receptor approach to characterize the volatile organic compounds
      from control device exhaust in a science park.
AB  - The science parks have helped shape Taiwan as a high-tech island with a good
      reputation worldwide. But some complaints on air pollution from the science parks
      have recently risen. To better understand the environmental effects of volatile
      organic compounds (VOCs) emitted from various high-tech factories in a science
      park, this study uses a source-receptor approach to characterize the
      environmental effects of VOCs from control device exhaust in Taichung Science
      Park. The chemical mass balance model (CMB8.2) of field measurements of 30 stacks
      and ambient air at nine sites was used to identify the source and relative
      contribution of ambient VOCs. The exhaust gas of various pollution control
      devices was also sampled by drawing a stream of the gases from the exhaust duct
      at its sampling port. The VOC source profile of each control device exhaust was
      determined using a database of noncharacteristic compounds. Monthly ambient
      concentrations of 167 VOCs were divided into monsoon datasets to investigate the
      effect of monsoon conditions on the emission of VOCs in the science park. This
      study also suggests a method for determining the optimum source profile in source
      receptor modeling, and identifies and analyzes the sources of ambient VOCs at
      nine sites during southwest and northeast monsoons. Results show a direct
      relationship between the relative contribution of each source and its control
      device efficiency. The proposed source-receptor approach can characterize the
      environmental effect of air pollutants from various factories and successfully
      assess the efficiency of various control devices.

PMID- 22869505
TI  - Spleen size in idiopathic and heritable pulmonary arterial hypertension.
AB  - BACKGROUND: It is unknown whether the spleen size correlates with disease
      severity and outcome in patients with idiopathic and heritable pulmonary arterial
      hypertension (PAH). OBJECTIVES: To determine the prevalence of splenomegaly in
      PAH and assess whether it correlates with severity of disease and outcome.
      METHODS: We identified subjects with either heritable or idiopathic PAH who had
      Doppler echocardiography, right-heart catheterization and computed tomography
      (CT) of the chest and/or abdomen that included the spleen. RESULTS: We included
      62 subjects with a mean age (+/-SD) of 49 (+/-15) years; 82% were women. Spleen
      dimensions were 10 (+/-3), 6 (+/-2) and 9 (+/-2) cm for the craniocaudal length,
      thickness and width measurements, respectively. The median [interquartile range
      (IQR)] spleen volume was 344 (225-533) cm3. Splenomegaly was observed in 52-63%
      of the patients, depending on the formula used. The spleen volume was not
      associated with clinical, echocardiographic or hemodynamic variables. Spleen
      volume was not associated with adjusted mortality. We studied the characteristics
      of the spleen during autopsy in 9 patients with idiopathic PAH who died of right
      heart failure. The mean (IQR) spleen weight was 220 (151-325) g. We observed
      early congestion in all but 2 patients who had chronic congestion. CONCLUSIONS:
      Splenomegaly of predominantly mild degree is common in idiopathic and heritable
      PAH. However, spleen size was not associated with clinical, echocardiographic,
      hemodynamic and survival data in these patients.

PMID- 22869506
TI  - Increasing photocurrents in dye sensitized solar cells with tantalum-doped
      titanium oxide photoanodes obtained by laser ablation.
AB  - Laser ablation is employed to produce vertically aligned nanostructured films of
      undoped and tantalum-doped TiO(2) nanoparticles. Dye-sensitized solar cells using
      the two different materials are compared. Tantalum-doped TiO(2) photoanode show
      65% increase in photocurrents and around 39% improvement in overall cell
      efficiency compared to undoped TiO(2). Electrochemical impedance spectroscopy,
      Mott-Schottky analysis and open circuit voltage decay is used to investigate the
      cause of this improved performance. The enhanced performance is attributed to a
      combination of increased electron concentration in the semiconductor and a
      reduced electron recombination rate.

PMID- 22869507
TI  - [Dementia guidelines: what should come to general practice--an interdisciplinary
      consensus of physicians in private practice].
AB  - BACKGROUND: Guidelines of Medical Societies aim at supporting the quality of
      medical care in general, and particularly in private practice. Usually,
      physicians in private practice are not part of the expert committees of medical
      societies that author guidelines. Guidelines represent a consensus appraising
      evidence from clinical studies on efficacy and side effects but also evaluating
      aspects of the health care system such as costs. Guidelines commonly do not
      account for regional specifics. Transfer of knowledge from guidelines to general
      practice, therefore, is incomplete. METHODS: We describe a consensus of
      neuropsychiatric and general physicians (n=12; 10 to 38 years of professional
      experience) on prioritization of diagnostic and therapeutic procedures for
      patients with Alzheimer's dementia as judged by relevance and practicability
      compared to the guideline of the Society for General Medicine (DEGAM-guideline
      No. 12) and the S3-guideline dementia of the German Society for Psychiatry,
      Psychotherapy and Neuropsychiatry (DGPPN). RESULTS: If patients and proxies do
      not oppose diagnosis, e. g. in cases of progressive impairment of memory with
      everyday relevance, the appropriate diagnostic procedures should be performed for
      every patient. Age or setting in which the patients live, in itself are no reason
      to limit antidementia therapy. Symptom fluctuations or decline of individual
      symptoms are compatible with treatment success. Clinical scales may only be used
      as supportive means to evaluate disease progression. CONCLUSION: Diagnosis and
      treatment of dementia are experienced as complex tasks by physicans in private
      practice. Practicing physicians need to adapt guidelines of medical societies on
      local and individual specifics.

PMID- 22869508
TI  - [Hepatic peliosis--a rare liver tumor and challenge for diagnostic investigation
      plus therapy].
AB  - HISTORY AND ADMISSION FINDINGS: A 42-year-old woman presented at our hospital,
      because of a non-specific hepatic tumor. She complained of dull pain in the right
      upper abdomen. Physical examination did not reveal any pathology, especially
      there was no evidence of an infection. Abuse of drugs, alcohol or
      anticontraceptives was also denied. INVESTIGATIONS UND THERAPY: Even though fine
      needle biopsy and extensive radiological examination were performed a malignant
      nature of the liver tumor could not be excluded. Therefore a hemihepatectomy was
      performed. TREATMENT AND COURSE: The postoperative course was normal and the
      patient was released from hospital after 11 days. The histological examination
      revealed an incidental finding of an extended peliosis hepatis. CONCLUSION:
      Peliosis hepatis is a rare disease of the liver, histologically characterized by
      blood filled cavities. The clinical picture of this disease is mostly
      asymptomatic, but it may also lead to liver failure, portal hypertention and
      massive intrahepatic bleeding. The preoperative differentiation is an
      interdisciplinary challenge, especially in terms of radiological examination
      (chemical shift MRI; liver specific radiocontrast). If the distinction to a
      malignancy cannot be excluded operative resection is indicated.

PMID- 22869510
TI  - [61-year-old patient with acute dyspnoe and holosystolic murmur].

PMID- 22869509
TI  - [Two patients with renal medullary hyperechogenicity].
AB  - HISTORY AND ADMISSION FINDINGS: We report two patients with medullary
      nephrocalcinosis and nephrolithiasis. The first patients had unspecific symptoms
      of a systemic inflammatory disease, the second patient was asymptomatic.
      INVESTIGATIONS: Both patients had normocalcemia and normal parathyroid hormone
      levels, very high 1,25(OH)(2)-vitamin D and normal to low 25-OH-vitamin D levels.
      On renal ultrasound, both patients displayed nephrocalcinosis and
      nephrolithiasis. DIAGNOSIS: Both patients showed dysregulation of the 1alpha
      hydroxylase activity. The first patient suffered from a systemic inflammatory
      disease with consecutive activation of macrophages with extrarenal alpha
      hydroxylase activity. The second patient had a "loss of function" mutation of the
      calcium sensing receptor with - for the situation - inadequatly high parathyroid
      hormone levels and consequently a renal dysregulation of the 1alpha-hydroxylase.
      TREATMENT AND COURSE: After immunosuppressive treatment with prednisolone and
      hydroxychloroquin there was complete remission of the systemic inflammatory
      disease in the first patient. In consequence the 1,25-(OH)(2)-vitamin D levels
      regressed and renal function stabilized. The second patient was completely
      asymptomatic with normal renal function, so far we did not initiate any
      treatment. CONCLUSIONS: Nephrocalcinosis and nephrolithiasis can result from
      hypercalciuria due to dysregulated hydroxylation of vitamin D. For both renal and
      extrarenal sources causal treatment is available.

PMID- 22869511
TI  - [Novel insights in cell death: implications for tumor pathology].

PMID- 22869512
TI  - [Off-label use of drugs--the legal framework].

PMID- 22869513
TI  - [New endovascular treatment options of deep vein thrombosis].

PMID- 22869515
TI  - Shockwave therapy in patients with peripheral artery disease.
AB  - INTRODUCTION: Previous studies support the fact that extracorporeal shockwave
      (SW) induces angiogenesis and improves symptoms in patients affected by limb
      ischemia. The aim of this study was to evaluate the effects of SW therapy in
      patients with peripheral artery disease (PAD). METHODS: Twenty-two patients were
      enrolled in this study and were randomly assigned into two groups: SW treatment
      (12 patients, 67 +/- 9 years) and control (10 patients, 68 +/- 12 years). The
      inclusion criteria were the following: age over 40 years, PAD diagnosis, optimal
      medical therapy, and ankle-brachial index less than 0.9. SW therapy was
      administered using the Minilith(r) SL1 litotriptor with an ultrasound guide able
      to detect the target area using a B-mode technique and a 7.5 MHz convex probe
      emitting 2,000 impulses with an energy flux density of 0.03 mJ/mm(2). RESULTS:
      The variation in the degree of stenosis before and after treatment was
      statistically significant between the groups (-9% +/- -10% vs. 0% +/- 0%; P =
      0.001). In addition, a significantly higher number of treated patients than
      controls showed a reduction in the Fontaine stage (12 [63%] vs. 0 [0%]; P <
      0.001). This result was confirmed by analyzing the difference in patients' pain
      free walking distance before and after SW therapy (76 +/- 46 m vs. 0 +/- 0 m for
      treated patients vs. controls; P < 0.001) and the difference in pain severity
      (measured on a pain scale; -1.4 +/- 0.5 in the treated patients vs. -0.2 +/- 0.4
      in the controls; P < 0.001). CONCLUSION: On the basis of these results the
      authors hypothesized a direct effect of SW on the ultrastructural composition of
      the vessel walls, inducing a reduction in artery stenosis. These data support the
      application of SW therapy as a new medical tool to improve the natural clinical
      course of PAD.

PMID- 22869517
TI  - Impact of bimetal electrodes on dielectric properties of TiO2 and Al-doped TiO2
      films.
AB  - Rutile structured Al-doped TiO(2) (ATO) and TiO(2) films were grown on bimetal
      electrodes (thin Ru/thick TiN, Pt, and Ir) for high-performance capacitors. The
      work function of the top Ru layer decreased on TiN and increased on Pt and Ir
      when it was thinner than ~2 nm, suggesting that the lower metal within the
      electrodes influences the work function of the very thin Ru layer. The use of the
      lower electrode with a high work function for bottom electrode eventually
      improves the leakage current properties of the capacitor at a very thin Ru top
      layer (<=2 nm) because of the increased Schottky barrier height at the interface
      between the dielectric and the bottom electrode. The thin Ru layer was necessary
      to achieve the rutile structured ATO and TiO(2) dielectric films.

PMID- 22869516
TI  - Condom use and concurrent partnering among heterosexually active, African
      American men: a qualitative report.
AB  - African Americans are overrepresented among heterosexual cases of HIV/AIDS in the
      USA. Inconsistent condom use and concurrent partnering are two sexual behaviors
      driving the heterosexual HIV epidemic in the African American community. To
      inform the development of an HIV prevention behavioral intervention to decrease
      concurrent partnering and increase condom use among African American heterosexual
      men, we conducted formative research, including 61 structured interviews, 5 focus
      groups with 25 men, and 30 in-depth qualitative interviews between July and
      December 2009. We used a grounded theoretical approach and categorizing
      strategies to code and analyze the qualitative data. Results around condom use
      confirmed earlier findings among heterosexual men in general: condoms diminish
      pleasure, interfere with erection, and symbolize infidelity. Although valued by
      some as a form of disease prevention and pregnancy prevention, condoms are often
      used only with specific types of female partners, such as new or casual partners,
      or due to visual risk assessment. Sex partner concurrency was described as
      normative and ascribed to men's "natural" desire to engage in a variety of sexual
      activities or their high sex drive, with little recognition of the role it plays
      in the heterosexual HIV epidemic. Fatherhood emerged among many men as a crucial
      life event and compelling motivation for reducing sexual risk behavior. Based on
      these results, we conclude that existing HIV prevention efforts to improve
      attitudes towards and motivate use of condoms either have not reached or have not
      been successful with African American heterosexual men. In designing behavioral
      interventions to decrease concurrent partnering and increase condom use,
      addressing negative attitudes towards condoms and partner risk assessment is
      critical, as is integrating novel motivational approaches related to identity as
      fathers and men in the African American community. 

PMID- 22869518
TI  - Tension pyopneumothorax due to a ruptured pulmonary echinococcal cyst.

PMID- 22869519
TI  - Preparation of a stable sol suspension of Pd-loaded SnO2 nanocrystals by a
      photochemical deposition method for highly sensitive semiconductor gas sensors.
AB  - A stable sol suspension of Pd-loaded SnO(2) nanocrystals, which is valid for both
      fundamental studies of semiconductor gas sensor and fabrications of a micro gas
      sensor, was fabricated by the photochemical deposition of PdCl(4)(2-) onto SnO(2)
      in an aqueous solution. UV light was irradiated on a mixture of a SnO(2) sol
      obtained through a hydrothermal treatment of stannic acid gel in the presence of
      PdCl(4)(2-) and ethanol/water at pH 2. A stable sol suspension of Pd-loaded
      SnO(2) was successfully obtained by controlling the pH of the above suspension to
      10.5 after UV irradiation. Thin-film type sensor devices (film thickness ~200 nm)
      using Pd-loaded SnO(2) nanocrystal were successfully fabricated by a spin-coating
      method. Gas sensing measurements showed that the deposition of Pd on the SnO(2)
      nanocrystals resulted in large electrical sensitization effect. The maximum gas
      sensitization effect was obtained at 0.125 mol % Pd loading. Moreover, the Pd
      loading lowered the temperature, in which the maximum sensor response to H(2) was
      obtained, due to the efficient catalytic combustion of H(2) on Pd.

PMID- 22869520
TI  - Association between angiotensin II Type 2 receptor gene A/C3123 polymorphism and
      high-density lipoprotein cholesterol with hypertension in asymptomatic women.
AB  - OBJECTIVE: The present study investigated the association between the angiotensin
      II type 2 receptor (AT2R) gene adenine/cytosine (A/C)-3123 polymorphism and
      cardiometabolic variables in subjects with and without hypertension. METHODS:
      Cardiometabolic variables, in addition to genotyping by an allele-specific DNA
      assay, were measured in 161 asymptomatic community-dwelling Japanese women (age
      range 30-83 years). They were divided into hypertensive (n = 82, age 50-81 years)
      and nonhypertensive (n = 79, age 30-83 years) subjects. RESULTS: The A-allele
      carriers (n = 53) showed significantly lower high-density lipoprotein cholesterol
      (HDL-C) levels than the non-A-allele carriers (n = 26) among nonhypertensive
      subjects (1.45 +/- 0.38 vs. 1.66 +/- 0.33 mmol/l, p = 0.02). Even when multiple
      adjusted analyses were performed, the HDL-C levels continued to differ
      significantly and independently of other variables, including the body mass index
      and insulin resistance index, between A-allele and non-A-allele carriers.
      However, this association was not observed among hypertensive subjects.
      CONCLUSION: The present study demonstrated that A-allele carriers had
      significantly lower HDL-C levels than did non-A-allele carries among
      nonhypertensive women, while this association was not observed among hypertensive
      women. This indicates that the A/C3124 polymorphism may be a marker associated
      with HDL metabolism by hypertension. This was a small study, so further research
      is warranted to confirm the observed association.

PMID- 22869521
TI  - The hypoxia-inducible factor-C/EBPalpha axis controls ethanol-mediated hepcidin
      repression.
AB  - Hepcidin is a liver-derived peptide hormone and the master regulator of systemic
      iron homeostasis. Decreased hepcidin expression is a common feature in alcoholic
      liver disease (ALD) and in mouse models of ethanol loading. Dysregulation of
      hepcidin signaling in ALD leads to liver iron deposition, which is a major
      contributing factor to liver injury. The mechanism by which hepcidin is regulated
      following ethanol treatment is unclear. An increase in liver hypoxia was observed
      in an acute ethanol-induced liver injury model. The hypoxic response is
      controlled by a family of hypoxia-inducible transcription factors (HIFs), which
      are composed of an oxygen-regulated alpha subunit (HIFalpha) and a constitutively
      present beta subunit, aryl hydrocarbon receptor nuclear translocator
      (HIFbeta/Arnt). Disruption of liver HIF function reversed the repression of
      hepcidin following ethanol loading. Mouse models of liver HIF overexpression
      demonstrated that both HIF-1alpha and HIF-2alpha contribute to hepcidin
      repression in vivo. Ethanol treatment led to a decrease in CCAAT-enhancer-binding
      protein alpha (C/EBPalpha) protein expression in a HIF-dependent manner.
      Importantly, adenoviral rescue of C/EBPalpha in vivo ablated the hepcidin
      repression in response to ethanol treatment or HIF overexpression. These data
      provide novel insight into the regulation of hepcidin by hypoxia and indicate
      that targeting HIFs in the liver could be therapeutic in ALD.

PMID- 22869522
TI  - Plk1 phosphorylates Sgt1 at the kinetochores to promote timely kinetochore
      microtubule attachment.
AB  - Accurate chromosome segregation during cell division maintains genomic integrity
      and requires the proper establishment of kinetochore-microtubule attachment in
      mitosis. As a key regulator of mitosis, Polo-like kinase 1 (Plk1) is essential
      for this attachment process, but the molecular mechanism remains elusive. Here we
      identify Sgt1, a cochaperone for Hsp90, as a novel Plk1 substrate during mitosis.
      We show that Sgt1 dynamically localizes at the kinetochores, which lack
      microtubule attachments during prometaphase. Plk1 is required for the kinetochore
      localization of Sgt1 and phosphorylates serine 331 of Sgt1 at the kinetochores.
      This phosphorylation event enhances the association of the Hsp90-Sgt1 chaperone
      with the MIS12 complex to stabilize this complex at the kinetochores and thus
      coordinates the recruitment of the NDC80 complex to form efficient microtubule
      binding sites. Disruption of Sgt1 phosphorylation reduces the MIS12 and NDC80
      complexes at the kinetochores, impairs stable microtubule attachment, and
      eventually results in chromosome misalignment to delay the anaphase onset. Our
      results demonstrate a mechanism for Plk1 in promoting kinetochore-microtubule
      attachment to ensure chromosome stability.

PMID- 22869523
TI  - beta1 integrin NPXY motifs regulate kidney collecting-duct development and
      maintenance by induced-fit interactions with cytosolic proteins.
AB  - Loss of beta1 integrin expression inhibits renal collecting-system development.
      Two highly conserved NPXY motifs in the distal beta1 tail regulate integrin
      function by associating with phosphtyrosine binding (PTB) proteins, such as talin
      and kindlin. Here, we define the roles of these two tyrosines in collecting
      system development and delineate the structural determinants of the distal beta1
      tail using nuclear magnetic resonance (NMR). Mice carrying alanine mutations have
      moderate renal collecting-system developmental abnormalities relative to beta1
      null mice. Phenylalanine mutations did not affect renal collecting-system
      development but increased susceptibility to renal injury. NMR spectra in bicelles
      showed the distal beta1 tail is disordered and does not interact with the model
      membrane surface. Alanine or phenylalanine mutations did not alter beta1
      structure or interactions between alpha and beta1 subunit
      transmembrane/cytoplasmic domains; however, they did decrease talin and kindlin
      binding. Thus, these studies highlight the fact that the functional roles of the
      NPXY motifs are organ dependent. Moreover, the beta1 cytoplasmic tail, in the
      context of the adjacent transmembrane domain in bicelles, is significantly
      different from the more ordered, membrane-associated beta3 integrin tail.
      Finally, tyrosine mutations of beta1 NPXY motifs induce phenotypes by disrupting
      their interactions with critical integrin binding proteins like talins and
      kindlins.

PMID- 22869524
TI  - SmD3 regulates intronic noncoding RNA biogenesis.
AB  - Accumulation of excess lipid in nonadipose tissues is associated with oxidative
      stress and organ dysfunction and plays an important role in diabetic
      complications. To elucidate molecular events critical for lipotoxicity, we used
      retroviral promoter trap mutagenesis to generate mutant Chinese hamster ovary
      cell lines resistant to lipotoxic and oxidative stress. A previous report of a
      mutant from this screen demonstrated that under lipotoxic conditions, small
      nucleolar RNAs (snoRNAs) in the rpL13a gene accumulate in the cytosol and serve
      as critical mediators of lipotoxic cell death. We now report a novel, independent
      mutant in which a single provirus disrupted one allele of the gene encoding the
      spliceosomal protein SmD3, creating a model of haploinsufficiency. We show that
      snoRNA expression and the abundance of snoRNA-containing intron lariats are
      decreased in SmD3 mutant cells, even though haploinsufficiency of SmD3 supports
      pre-mRNA splicing. The mechanism through which SmD3 regulates the expression of
      intronic snoRNAs likely involves effects of SmD3 on the levels of small nuclear
      RNAs (snRNAs) U4 and U5. Our data implicate SmD3 as a critical determinant in the
      processing of intronic noncoding RNAs in general and as an upstream mediator of
      metabolic stress response pathways through the regulation of snoRNA expression.

PMID- 22869525
TI  - Insulin-like growth factor (IGF) binding protein 2 functions coordinately with
      receptor protein tyrosine phosphatase beta and the IGF-I receptor to regulate IGF
      I-stimulated signaling.
AB  - Insulin-like growth factor I (IGF-I) is a mitogen for vascular smooth muscle
      cells (VSMC) and has been implicated in the development and progression of
      atherosclerosis. IGF binding proteins (IGFBPs) modify IGF-I actions independently
      of IGF binding, but a receptor-based mechanism by which they function has not
      been elucidated. We investigated the role of IGFBP-2 and receptor protein
      tyrosine phosphatase beta (RPTPbeta) in regulating IGF-I signaling and cellular
      proliferation. IGFBP-2 bound RPTPbeta, which led to its dimerization and
      inactivation. This enhanced PTEN tyrosine phosphorylation and inhibited PTEN
      activity. Utilization of substrate trapping and phosphatase-dead mutants showed
      that RPTPbeta bound specifically to PTEN and dephosphorylated it. IGFBP-2
      knockdown led to decreased PTEN tyrosine phosphorylation and decreased AKT Ser473
      activation. IGFBP-2 enhanced IGF-I-stimulated VSMC migration and proliferation.
      Analysis of aortas obtained from IGFBP-2(-/-) mice showed that RPTPbeta was
      activated, and this was associated with inhibition of IGF-I stimulated AKT Ser473
      phosphorylation and VSMC proliferation. These changes were rescued following
      administration of IGFBP-2. These findings present a novel mechanism for
      coordinate regulation of IGFBP-2 and IGF-I signaling functions that lead to
      stimulation of VSMC proliferation. The results have important implications for
      understanding how IGFBPs modulate the cellular response to IGF-I.

PMID- 22869526
TI  - A distinct Smoothened mutation causes severe cerebellar developmental defects and
      medulloblastoma in a novel transgenic mouse model.
AB  - Deregulated developmental processes in the cerebellum cause medulloblastoma, the
      most common pediatric brain malignancy. About 25 to 30% of cases are caused by
      mutations increasing the activity of the Sonic hedgehog (Shh) pathway, a critical
      mitogen in cerebellar development. The proto-oncogene Smoothened (Smo) is a key
      transducer of the Shh pathway. Activating mutations in Smo that lead to
      constitutive activity of the Shh pathway have been identified in human
      medulloblastoma. To understand the developmental and oncogenic effects of two
      closely positioned point mutations in Smo, we characterized NeuroD2-SmoA2 mice
      and compared them to NeuroD2-SmoA1 mice. While both SmoA1 and SmoA2 transgenes
      cause medulloblastoma with similar frequencies and timing, SmoA2 mice have severe
      aberrations in cerebellar development, whereas SmoA1 mice are largely normal
      during development. Intriguingly, neurologic function, as measured by specific
      tests, is normal in the SmoA2 mice despite extensive cerebellar dysplasia. We
      demonstrate how two nearly contiguous point mutations in the same domain of the
      encoded Smo protein can produce striking phenotypic differences in cerebellar
      development and organization in mice.

PMID- 22869529
TI  - [How traumatized are the children of World War II? The relationship of age during
      flight and forced displacement and current posttraumatic stress symptoms].
AB  - Traumatic events experienced in childhood can be reactivated in older age. The
      present study investigates the relation of age during flight and forced
      displacement within World War II (WWII; 2-7 years, 8-13 years, 14-20 years) and
      the current occurrence of posttraumatic stress disorder (PTSD). Traumatic events
      and current posttraumatic stress symptoms were assessed by the Harvard Trauma
      Questionnaire and the Impact of Event Scale-revised. Mean age of participants
      (N=169) was 73.76 years (SD=4.18). The eldest group reported most war-related
      traumatic events. In each age group a one-week-prevalence for a full PTSD of 10
      11% was found. The prevalence for both full and subthreshold PTSD was higher for
      the age group 14-20 years (60.5%) compared to the younger age groups (33-35%).
      People, who experienced WWII as adolescents, show a dose-response-effect
      indicated by a higher prevalence for subthreshold PTSD.

PMID- 22869527
TI  - Multiple cancer testis antigens function to support tumor cell mitotic fidelity.
AB  - While the expression of genes that are normally involved in spermatogenesis is
      frequently detected in tumors, the extent to which these gene products are
      required for neoplastic behaviors is unclear. To begin to address their
      functional relevance to tumorigenesis, we identified a cohort of proteins which
      display synthetic lethality with paclitaxel in non-small-cell lung cancer and
      whose expression is biased toward testes and tumors. Remarkably, these testis
      proteins, FMR1NB, NXF2, MAGEA5, FSIP1, and STARD6, are required for accurate
      chromosome segregation in tumor cells. Their individual depletion enhances the
      generation of multipolar spindles, increases mitotic transit time, and induces
      micronucleation in response to an otherwise innocuous dose of paclitaxel. The
      underlying basis for abnormal mitosis is an alteration in microtubule function,
      as their depletion increases microtubule cytaster formation and disrupts
      microtubule stability. Given these observations, we hypothesize that reactivated
      testis proteins may represent unique tumor cell vulnerabilities which, if
      targeted, could enhance responsiveness to antimitotic therapy. Indeed, we
      demonstrate that combining paclitaxel with a small-molecule inhibitor of the
      gametogenic and tumor cell mitotic protein TACC3 leads to enhanced centrosomal
      abnormalities, activation of death programs, and loss of anchorage-independent
      growth.

PMID- 22869530
TI  - [Changes in psychopathological symptoms during the waiting period for outpatient
      psychotherapy].
AB  - This study empirically tests symptom changes in a sample of 106 psychotherapy
      outpatients during a 6-month waiting period before treatment commencement. Using
      indirect measurement of change, the patients improve in psychopathological
      symptoms. Using direct measurement of change, 48% of the outpatients show no
      significant change in psychopathological symptoms. However, the symptoms of 29%
      improve and 23% worsen. Using multinomial logistic regression, group membership
      (no change, positive change, negative change) can be predicted by personality
      traits for 60% of the patients. Social trust negatively predicts changes for the
      worse. Liberal gender-role orientation positively predicts improvement. A
      positive self-concept of ability positively predicts changes for the worse.
      Moreover sociodemographic variables correctly predict group membership for 57% of
      the patients. Age positively predicts changes for the worse. Female gender
      negatively predicts improvement.

PMID- 22869531
TI  - [Parenting facts and desires in relation to sexual orientation and gender
      identity].
AB  - Homosexual parents as well as gay and lesbian individuals wanting children are
      increasingly a topic of public discourse. To estimate the importance of parenting
      for this group, 1 289 non-heterosexual individuals were examined by means of an
      anonymous online survey. Their answers were compared to 1 022 heterosexual
      participants of a representative control group. The respondents were questioned
      concerning their motives for desiring children, the external factors influencing
      this desire and their ideal number of children. 80% of the non-heterosexual
      respondents and 49% of the control group indicated that they have no children. In
      both groups emotional motives were reported to have far greater influence on
      their parenting desire than social recognition or personal and financial
      constraints. 85% of the non-heterosexual respondents and 60% of the control group
      have fewer children than they would like to have. Both groups considered work and
      their financial situation as the most important external factors influencing the
      realization of their desire to have children.

PMID- 22869532
TI  - [The sample: does size matter?].

PMID- 22869533
TI  - [Clinical diagnostics and therapy of chronic pain syndromes].

PMID- 22869535
TI  - Photomagnetism in cyano-bridged bimetal assemblies.
AB  - The study of photoinduced phase-transition materials has implications for the
      fields of inorganic chemistry, solid-state chemistry, and materials science.
      Cyano-bridged bimetal assemblies are promising photomagnetic materials. Because
      cyano-bridged bimetal assemblies possess various absorption bands in the visible
      light region, their electronic and spin states can be controlled by visible light
      irradiation. Moreover, the selection of magnetic metal ions and organic ligands
      provide a way of controlling spin-spin interactions through a cyano bridge. In
      this Account, we describe cyano-bridged bimetal assemblies developed in our
      laboratory. Cu(II)(2)[Mo(IV)(CN)(8)].8H(2)O (CuMo), Rb(I)Mn(II)[Fe(III)(CN)(6)]
      (RbMnFe), and Co(II)(3)[W(V)(CN)(8)](2).(pyrimidine)(4).6H(2)O (CoW) induce
      photomagnetism via photoinduced metal-to-metal charge transfers (MM'CT), while
      Fe(II)(2)[Nb(IV)(CN)(8)].(4-pyridinealdoxime)(8).2H(2)O (FeNb) exhibits a
      photoinduced magnetization via a photoinduced spin crossover. Irradiation with
      473 nm light causes the CuMo system to exhibit a spontaneous magnetization with a
      Curie temperature (T(C)) of 25 K, but irradiation with 532, 785, and 840 nm light
      reduces the magnetization. In this reversible photomagnetic process, excitation
      of the MM'CT from Mo(IV) to Cu(II) produces a ferromagnetic mixed-valence isomer
      of Cu(I)Cu(II)[Mo(V)(CN)(8)].8H(2)O (CuMo'). CuMo' returns to CuMo upon
      irradiation in the reverse-M'MCT band. RbMnFe shows a charge transfer (CT)
      induced phase transition from the Mn(II)-Fe(III) phase to the Mn(III)-Fe(II)
      phase. Irradiation with 532 nm light converts the Mn(III)-Fe(II) phase into the
      Mn(II)-Fe(III) phase, and we observe photodemagnetization. In contrast,
      irradiation of the Mn(II)-Fe(III) phase with 410 nm light causes the reverse
      phase transition. A CT-induced Jahn-Teller distortion is responsible for this
      visible light-induced reversible photomagnetic effect. In the CoW system, a CT
      induced spin transition causes the thermal phase transition from the Co(II)-W(V)
      phase to the Co(III)-W(IV) phase. Irradiation of the Co(III)-W(IV) phase with 840
      nm light causes ferromagnetism with a T(C) of 40 K and magnetic coercive field
      (H(c)) of 12,000 Oe, but excitation of the back M'MCT (Co(II) -> W(V)) with 532
      nm light leads to the reverse phase transition. These examples of the
      photomagnetic effect have occurred by exciting MM'CT bands. In the fields of
      inorganic chemistry and materials science, researchers have studied extensively
      the photoinduced phase transitions between low-spin (LS) and high-spin (HS)
      transition metal ions. Recently, we have observed the first example of
      photoinduced spin crossover ferromagnetism with a FeNb system (T(C) = 20 K and
      H(c) = 240 Oe), in which a strong superexchange interaction between photoproduced
      Fe(II)(HS) and neighboring paramagnetic Nb(IV) operates through a CN bridge. The
      optical switching magnets described in this Account may lead to novel optical
      recording technologies such as optomagnetic memories and optical computers.

PMID- 22869534
TI  - Comparative study of conventional lateral internal sphincterotomy, V-Y anoplasty,
      and tailored lateral internal sphincterotomy with V-Y anoplasty in the treatment
      of chronic anal fissure.
AB  - BACKGROUND: Lateral internal sphincterotomy has been proven highly effective in
      curing anal fissure but with a high incidence of postoperative incontinence.
      OBJECTIVE: We compared conventional lateral internal sphincterotomy, V-Y
      advancement flap, and combined tailored lateral internal sphincterotomy with V-Y
      advancement flap in treating anal fissure. PATIENTS: Consecutive patients treated
      for anal fissure at our colorectal unit were evaluated for inclusion.
      Participants were randomly allocated to receive conventional sphincterotomy (GI),
      V-Y advancement flap (GII), or combined tailored lateral sphincterotomy with V-Y
      advancement l flap (GIII). MAIN OUTCOME MEASURES: The primary outcome measure was
      the incontinence rate; secondary outcomes included healing rate, operative time,
      anal manometery, and recurrence rate. RESULTS: One hundred fifty patients with
      chronic anal fissure were randomized. Healing rate after 1 year was 84% in GI,
      48% in GII, and 94% in GIII, respectively (P = 0.001). The recurrence rate was 4%
      in G1, 22% in GII, and 2% in GIII (P = 0.01). Incontinence rate was 14% in GI, 0%
      in GII, and 2% in GIII (P = 0.03). CONCLUSION: Although all three procedures are
      simple and easy to perform, tailored lateral internal sphincterotomy with V-YF
      appears to produce the greatest healing rate, with the fewest complications and
      less rate of recurrence.

PMID- 22869536
TI  - Association of RGA-SSCP markers  with resistance to downy mildew and anthracnose
      in  grapevines.
AB  - Downy  mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum)  are
      two major diseases that severely affect most grapevine (Vitis vinifera) 
      cultivars grown commercially in Thailand. Progress of conventional breeding 
      programs of grapevine for improved resistance to these diseases can be speeded 
      up by selection of molecular markers associated with resistance traits. We 
      evaluated the association between 13 resistance gene analog (RGA)-single-strand 
      conformation polymorphism (SSCP) markers with resistance to downy mildew and 
      anthracnose in 71 segregating progenies of seven cross combinations between 
      susceptible cultivars and resistant lines. F(1) hybrids from  each cross were
      assessed for resistance to downy mildew and anthracnose  (isolates Nk4-1 and Rc2
      1) under laboratory conditions. Association of  resistance traits with RGA-SSCP
      markers was evaluated using simple linear  regression analysis. Three RGA-SSCP
      markers were found to be significantly correlated  with anthracnose resistance,
      whereas significant correlation with downy mildew  resistance was observed for
      only one RGA-SSCP marker. These results demonstrate  the usefulness of RGA-SSCP
      markers. Four candidate markers with significant  associations to resistance to
      these two major diseases of grapevine were  identified. However, these putative
      associations between markers and resistance  need to be verified with larger
      segregating populations before they can be used  for marker-assisted selection.

PMID- 22869537
TI  - Induced mitotic  homologous recombination by the babesicide imidocarb
      dipropionate in Aspergillus  nidulans diploid cells.
AB  - Imidocarb  dipropionate (IMD) is a chemotherapeutic agent prescribed for the
      treatment and  control of babesiosis; it is known to be a nucleic acid synthesis
      inhibitor.  Although it is an effective babesicide, there are reports of
      persistent IMD  residues retained at high levels in edible tissues of cattle,
      swine and sheep,  raising concerns about potential effects on humans. Since the
      carcinogenic  potential of a chemical compound can be assessed through its effect
      on the  homologous recombination, we investigated whether IMD is recombinogenic
      in Aspergillus  nidulans diploid cells and whether it is capable of inducing
      homozygosis in  genes that were previously heterozygous. This analysis was done
      with a  homozygotization assay applied to a heterozygous diploid strain of A. 
      nidulans. IMD used at non-toxic concentrations (2.5 to 10.0 MUM) was 
      recombinogenic, demonstrated by homozygotization indices higher than 2.0 for 
      diploid markers. A diploid homozygous for genetic markers from chromosomes I  and
      II was also produced. Since DNA replication blockers that induce DNA strand 
      breaks have been classified as potent inducers of homologous recombination, the 
      recombinogenic potential of IMD may be due to induction of recombinational 
      repair.

PMID- 22869538
TI  - Estimation of  genetic parameters for partial egg production periods by means of
      random  regression models.
AB  - We  estimated genetic parameters for egg production in different periods by means
      of random regression models, aiming at selection based on partial egg 
      production from a generation of layers. The production was evaluated for each 
      individual by recording the number of eggs produced from 20 to 70 weeks of age, 
      with partial records taken every three weeks for a total of 17 periods. The 
      covariance functions were estimated with a random regression model by the 
      restricted maximum likelihood method. A model composed of third-order 
      polynomials for the additive effect, ninth-order polynomials for the permanent 
      environment, and a residual variance structure with five distinct classes, was 
      found to be most suitable for adjusting the egg production data for laying  hens.
      The heritability estimates varied from 0.04 to 0.14. The genetic  correlations
      were all positive, varying from 0.10 to 0.99. Selection applied in  partial egg
      production periods will result in greater genetic profit for the  adjacent
      periods. However, as the distance in time between periods increases,  selection
      becomes less efficient. Selection based on the second period (23 to  25 weeks of
      age), where greater heritability was estimated, would note benefit  the final egg
      laying cycle periods.

PMID- 22869539
TI  - Histochemical  map of the ectopic expression of the Arabidopsis atExt1 extensin
      gene in  transgenic tobacco.
AB  - Histochemical  analysis of transgenic tobacco plants harboring the promoter of
      the Arabidopsis extensin gene atExt1 fused to the beta-glucuronidase gene coding
      sequence  demonstrated expression of the transgene in stem tissues. The transgene
      was  expressed in cells of the internal and external phloem at the nodal and 
      internodal regions of the older parts of mature stems. In younger parts of the 
      same stem, expression of the transgene was slightly modified: expression was 
      detected in the internal phloem in the internodal areas. In the nodal areas,  the
      phloem tissue and the surrounding parenchyma were stained, demonstrating 
      transgene expression. Expression was also seen in the phloem of the 
      inflorescence; it was non-specific at the junctions of the flowers to the 
      inflorescence. beta-glucuronidase  (reporter gene) staining was also observed in
      the pollen grains and at the base  of the corolla.

PMID- 22869540
TI  - Plasma resistin,  associated with single nucleotide polymorphism -420, is
      correlated with  C-reactive protein in Chinese Han patients with spontaneous
      basal ganglia  hemorrhage.
AB  - We  examined a possible relationship -420C>G SNP of the resistin gene with plasma
      resistin and C-reactive protein concentrations in intracerebral hemorrhage. 
      Three hundred and forty-four Chinese Han patients with intracerebral hemorrhage 
      and 344 age- and gender-matched healthy controls were included in our study. 
      Plasma resistin and C-reactive concentrations were measured and SNP -420C>G  was
      genotyped. The genotype frequencies in controls and patients were not 
      significantly different (P = 0.672). Plasma resistin and C-reactive protein 
      levels were significantly different between the SNP -420C>G genotypes, even 
      after adjustment for age, gender and body mass index. The common homozygote  (C
      C) had the lowest resistin and C-reactive protein plasma concentrations; the 
      plasma resistin and C-reactive protein concentrations in the heterozygote (C-G) 
      and the rare allele homozygote (G-G) did not differ significantly. Plasma 
      resistin levels were significantly associated with plasma C-reactive protein 
      level. We conclude that SNP -420C>G of the resistin gene could be involved  in
      the inflammatory component of intracerebral hemorrhage through enhanced 
      production of resistin.

PMID- 22869541
TI  - Selection  of high heterozygosity popcorn varieties in Brazil based on SSR
      markers.
AB  - We analyzed genetic structure and  diversity among eight populations of popcorn,
      using SSR loci as genetic  markers. Our objectives were to select SSR loci that
      could be used to estimate  genetic diversity within popcorn populations, and to
      analyze the genetic  structure of promising populations with high levels of
      heterozygosity that  could be used in breeding programs. Fifty-seven alleles (3.7
      alleles per locus)  were detected; the highest effective number of alleles (4.21)
      and the highest  gene diversity (0.763) were found for the Umc2226 locus. A very
      high  level of population differentiation was found (F(ST) = 0.3664), with F(ST)
      for each locus ranging from 0.1029 (Umc1664) to 0.6010 (Umc2350).  This analysis
      allowed us to identify SSR loci with high levels of  heterozygosity and
      heterozygous varieties, which could be selected for  production of inbred lines
      and for developing new cultivars.

PMID- 22869542
TI  - Use of transgenic seeds in Brazilian agriculture and  concentration of
      agricultural production to large agribusinesses.
AB  - We identified the commercial releases of genetically  modified organisms (GMOs)
      in Brazil, their characteristics, the types of  genetic transformation used, and
      the companies responsible for the development  of these GMOs, classifying them
      into two categories: private companies,  subdivided into multinational and
      national, and public institutions. The data  came from the data bank of the
      national registration of cultivars and the  service of national protection of
      cultivars of the Ministry of Agriculture,  Fishing and Supply (MAPA). This survey
      was carried out from 1998 to February  12, 2011. Until this date, 27 GMOs had
      been approved, including five for  soybean, 15 for maize and seven for cotton
      cultivars. These GMOs have been used  for the development of 766 cultivars, of
      which, 305 are soybean, 445 are maize,  and 13 are cotton cultivars. The Monsato
      Company controls 73.2% of the  transgenic cultivars certified by the MAPA; a
      partnership between Dow  AgroSciences and DuPont accounts for 21.4%, and Syngenta
      controls 4.96%. Seed  supply by these companies is almost a monopoly supported by
      law, giving no  choice for producers and leading to the fast replacement of
      conventional  cultivars by transgenic cultivars, which are expensive and exclude
      small  producers from the market, since seeds cannot be kept for later use. This 
      situation concentrates production in the hands of a few large national
      agribusiness  entrepreneurs.

PMID- 22869543
TI  - Genetic characterization of Red Junglefowl (Gallus  gallus), Thai indigenous
      chicken (Gallus domesticus), and two  commercial lines using selective functional
      genes compared to microsatellite  markers.
AB  - Genetic characterization among Red Junglefowl (GS, Gallus  gallus spadiceus),
      Thai indigenous chicken (TIC, Gallus domesticus)  and commercial lines has been
      widely used for studies of genealogical origin,  genetic diversity, and effects
      of selection. We compared the efficiency of  genetic characterization of chicken
      populations that had been under different  intensities of selection using
      selective functional gene versus microsatellite marker  analyses. We genotyped
      151 chickens from five populations: Red Junglefowl, TIC  and commercial lines
      (BR, broiler and WL, White Leghorn). Genetic structure  analyses using six loci
      of five functional genes - corresponding to heat  tolerance (heat shock protein
      70, HSP70/C, HSP70/M), broodiness  (vasoactive intestinal peptide receptor-1,
      VIPR-1), egg  production-[24-bp indel (insertion or deletion) prolactin,
      24bpPRL],  ovulation rate (growth hormone receptor, GHR), and growth (insulin
      like  growth factor-1, IGF-1) - were compared with 18 microsatellite markers. 
      PCR-RFLP and allele specific PCR were used for functional gene typing. A 
      neighbor-joining tree from Nei's genetic distance was constructed to show 
      genetic relationships. A similar pattern was found with both functional genes 
      and microsatellites. Three groups consisting of BR, WL and TIC-GS-GG were 
      formed. A principal component plot based on individual similarity using Dice's 
      coefficient was also constructed to confirm the relationship. Different  patterns
      were found when using functional genes versus microsatellites. A  principal
      component plot with functional genes also gave three clusters  consisting of BR,
      WL and TIC-GS-GG. A principal component plot using  microsatellites gave four
      clusters, consisting of WL, GG, TIC, and BR-GS. Characterization  of BR and GS
      differs from previous studies. We concluded that genetic  characterization with
      appropriate functional genes is more accurate when  differences in genetic make
      up among populations are known. Genetic  characterization using functional gene
      data was consistent in neighbor joining  and principal component plot analyses,
      while genetic characterization using  microsatellite data gave varied results
      depending on the analysis methodology.

PMID- 22869544
TI  - Age-related  changes in the surface pheromones of the wasp Mischocyttarus
      consimilis (Hymenoptera:  Vespidae).
AB  - One  of the most important attributes that allowed the evolution and maintenance
      of  sociality in insects is their ability to distinguish members of their own 
      colonies. The capacity for individual recognition in social insects is mediated 
      by chemical signals that are acquired soon after the adult emerges, and vary 
      according to the tasks performed by individuals in their colonies. We  determined
      the time when adults of the wasp Mischocyttarus consimilis acquire  the chemical
      signature of their colonies, as well as the variation in the  cuticular
      hydrocarbon profiles of the exoskeleton of individuals, according to  their
      functions in the colony. The method used was Fourier transform infrared 
      photoacoustic spectroscopy directly on the gaster of each individual. Young 
      wasps take three to four days to acquire the colony's chemical signature, with  a
      small change on the fifth day, when the cuticular hydrocarbon profile of the 
      workers is more similar to that of the queens than that of the males, probably 
      because they are of the same sex, but primarily because of the similarity of 
      tasks executed by these two groups of females in the colonies.

PMID- 22869545
TI  - Protein  transduction domain-hA20 fusion protein protects endothelial cells
      against high  glucose-induced injury.
AB  - We  constructed a plasmid containing a protein transduction domain (PTD) and a 
      human A20 (hA20) gene fragment; the fusion protein was obtained by highly 
      expressing this plasmid in the yeast Pichia pastoris GS115. The plasmid  was
      obtained by adding 9xArg and EcoRI recognition sites to the end of the primer,
      and  6xHis-Tag and NotI  recognition sites to its end. After sequencing, the hA20
      gene fragment was  inserted into plasmid pPIC9k to construct expression vector
      pPIC9k-PTD-hA20;  then, we transfected GS115 with the vector and induced PTD-hA20
      protein  expression. We purified protein from the yeast fermentation supernatant
      using a  nickel column. Human umbilical vein endothelial cells (HUVECs) were
      cultured in  high glucose medium (30 mM glucose) and in high glucose medium
      containing  different concentrations of protein. Apoptosis of HUVECs was assayed
      by TUNEL  72 h later. The biological activity tests indicated that the fusion
      protein not  only passed through the cell membrane freely, but also inhibited
      apoptosis of  HUVECs induced by high glucose levels. We conclude that the fusion
      protein  PTD-hA20 has potential for clinical use.

PMID- 22869546
TI  - FastJoin, an improved neighbor-joining algorithm.
AB  - Reconstructing the evolutionary history of a set of  species is an elementary
      problem in biology, and methods for solving this  problem are evaluated based on
      two characteristics: accuracy and efficiency.  Neighbor-joining reconstructs
      phylogenetic trees by iteratively picking a pair  of nodes to merge as a new node
      until only one node remains; due to its good  accuracy and speed, it has been
      embraced by the phylogeny research community.  With the advent of large amounts
      of data, improved fast and precise methods for  reconstructing evolutionary trees
      have become necessary. We improved the  neighbor-joining algorithm by iteratively
      picking two pairs of nodes and  merging as two new nodes, until only one node
      remains. We found that another  pair of true neighbors could be chosen to merge
      as a new node besides the pair  of true neighbors chosen by the criterion of the
      neighbor-joining method, in  each iteration of the clustering procedure for the
      purely additive tree. These  new neighbors will be selected by another iteration
      of the neighbor-joining  method, so that they provide an improved neighbor
      joining algorithm, by  iteratively picking two pairs of nodes to merge as two new
      nodes until only one  node remains, constructing the same phylogenetic tree as
      the neighbor-joining  algorithm for the same input data. By combining the
      improved neighbor-joining  algorithm with styles upper bound computation
      optimization of RapidNJ and  external storage of ERapidNJ methods, a new method
      of reconstructing  phylogenetic trees, FastJoin, was proposed. Experiments with
      sets of data  showed that this new neighbor-joining algorithm yields a
      significant speed-up  compared to classic neighbor-joining, showing empirically
      that FastJoin is  superior to almost all other neighbor-joining implementations.

PMID- 22869547
TI  - Shortening of the cell cycle and developmental interruption in a Dictyostelium 
      discoideum  cell line due to RNAi-silenced expression of allantoicase.
AB  - The signaling molecules NH(3) (unprotonated  volatile ammonia), as well as cyclic
      adenosine monophosphate and  differentiation-inducing factor, play important
      roles in the multicellular  development of the slime mould Dictyostelium
      discoideum. One of the  downstream metabolic products catalyzed by allantoicase
      (allC) is ammonia. We  observed the role of allC by RNAi-mediated manipulation of
      its expression. The  allC gene of D. discoideum was silenced by RNAi. We found
      significant  downregulation of allC mRNA and protein expression levels.
      Recombinant allC  RNAi mutant cell lines had a shortened cell cycle, a reduction
      in cell size  relative to wild-type cells and interrupted development. We
      conclude that the  normal functions of allC include retarding cell division until
      a specific cell  size is reached and coordinating the progression of development.

PMID- 22869548
TI  - DNA barcoding of  arid wild plants using rbcL gene sequences.
AB  - DNA  barcoding is currently gaining popularity due to its simplicity and high 
      accuracy as compared to the complexity and subjective biases associated with 
      morphology-based identification of taxa. The standard chloroplast DNA barcode 
      for land plants recommended by the Consortium for the Barcode of Life (CBOL) 
      plant working group needs to be evaluated for a wide range of plant species. We 
      therefore tested the potential of the rbcL marker for the identification  of wild
      plants belonging to diverse families of arid regions. Maximum  likelihood tree
      analysis was performed to evaluate the discriminatory power of  the rbcL gene.
      Our findings showed that using rbcL gene sequences  enabled identification of the
      majority of the samples (92%) to genus level and  only 17% to species level.

PMID- 22869549
TI  - Mendelian inheritance, linkage and genotypic  disequilibrium in microsatellite
      loci isolated from Hymenaea courbaril (Leguminosae).
AB  - The Neotropical tree Hymenaea courbaril,  locally known as Jatoba, is a valuable
      source of lumber and also produces comestible  and medicinal fruit. We
      characterized Mendelian inheritance, linkage and  genotypic disequilibrium at
      nine microsatellite loci isolated from H.  courbaril, in order to determine if
      they would provide accurate estimates  of population genetic parameters of this
      important Amazon species. The study  was made on 250 open-pollinated offspring
      originated from 14 seed trees. Only  one of nine loci presented significant
      deviation from the expected Mendelian  segregation (1:1). Genotypic
      disequilibrium between pairwise loci was  investigated based on samples from 55
      adult and 56 juvenile trees. No genetic  linkage between any paired loci was
      observed. After Bonferroni's corrections  for multiple tests, we found no
      evidence of genotypic disequilibrium between  pairs of loci. We conclude that
      this set of loci can be used for genetic diversity/  structure, mating system,
      gene flow, and parentage analyses in H. courbaril populations.

PMID- 22869550
TI  - Genetic and molecular mechanisms of  aluminum  tolerance in plants.
AB  - Aluminum (Al) toxicity restricts root growth and  agricultural yield in acid
      soils, which constitute approximately 40% of the  potentially arable lands
      worldwide. The two main mechanisms of Al tolerance in  plants are internal
      detoxification of Al and its exclusion from root cells.  Genes encoding membrane
      transporters and accessory transcription factors, as  well as cis-elements that
      enhance gene expression, are involved in Al  tolerance in plants; thus studies of
      these genes and accessory factors should  be the focus of molecular breeding
      efforts aimed at improving Al tolerance in  crops. In this review, we describe
      the main genetic and molecular studies that  led to the identification and
      cloning of genes associated with Al tolerance in  plants. We include recent
      findings on the regulation of genes associated with  Al tolerance. Understanding
      the genetic, molecular, and physiological aspects  of Al tolerance in plants is
      important for generating cultivars adapted to acid  soils, thereby contributing
      to food security worldwide.

PMID- 22869551
TI  - Clarification of data for a meta-analysis: p53 codon 72 polymorphism and prostate
      cancer risk.

PMID- 22869552
TI  - Detection of  bacterial blight resistance genes in basmati rice landraces.
AB  - Aromatic  basmati rice is vulnerable to bacterial blight disease. Genes
      conferring  resistance to bacterial blight have been identified in coarse rice;
      however,  their incorporation into basmati varieties compromises the prized
      basmati  aroma. We identified bacterial blight resistance genes Xa4, xa5, Xa7, 
      and xa13 in 52 basmati landraces and five basmati cultivars using PCR  markers.
      The Xa7 gene was found to be the most prevalent among the  cultivars and
      landraces. The cultivars Basmati-385 and Basmati-2000 also  contained the Xa4
      gene; however, xa5 and xa13 were  confined to landraces only. Ten landraces were
      found to have multiple  resistance genes. Landraces Basmati-106, Basmati-189 and
      Basmati-208 contained Xa4 and Xa7 genes. Whereas, landraces Basmati-122, Basmati
      427,  Basmati-433 were observed to have xa5 and Xa7 genes. Landraces  Basmati-48,
      Basmati-51A, Basmati-334, and Basmati-370A possessed Xa7 and xa13 genes. The use
      of landraces containing recessive genes xa5 and xa13 as donor parents in
      hybridization with cultivars Basmati-385 and  Basmati-2000, which contain the
      genes Xa4 and Xa7, will expedite  efforts to develop bacterial blight-resistant
      basmati rice cultivars through marker  assisted selection, based on a pyramiding
      approach, without compromising aroma  and grain quality.

PMID- 22869553
TI  - Interactome-wide analysis identifies end-binding protein 1 as a crucial component
      for the speck-like particle formation of activated absence in melanoma 2 (AIM2)
      inflammasomes.
AB  - Inflammasomes are cytoplasmic receptors that can recognize intracellular
      pathogens or danger signals and are critical for interleukin 1beta production.
      Although several key components of inflammasome activation have been identified,
      there has not been a systematic analysis of the protein components found in the
      stimulated complex. In this study, we used the isobaric tags for relative and
      absolute quantification approach to systemically analyze the interactomes of the
      NLRP3, AIM2, and RIG-I inflammasomes in nasopharyngeal carcinoma cells treated
      with specific stimuli of these interactomes (H2O2, poly (dA:dT), and EBV
      noncoding RNA, respectively). We identified a number of proteins that appeared to
      be involved in the interactomes and also could be precipitated with anti
      apoptosis-associated speck-like protein containing caspase activation and
      recruitment domain antibodies after stimulation. Among them, end binding protein
      1 was an interacting component in all three interactomes. Silencing of end
      binding protein 1 expression by small interfering RNA inhibited the activation of
      the three inflammasomes, as indicated by reduced levels of interleukin 1beta
      secretion. We confirmed that end binding protein 1 directly interacted with AIM2
      and ASC in vitro and in vivo. Most importantly, fluorescence confocal microscopy
      showed that end binding protein 1 was required for formation of the speck-like
      particles that represent activation of the AIM2 inflammasome. In nasopharyngeal
      carcinoma tissues, immunohistochemical staining showed that end binding protein 1
      expression was elevated and significantly correlated with AIM2 and ASC expression
      in nasopharyngeal carcinoma tumor cells. In sum, we profiled the interactome
      components of three inflammasomes and show for the first time that end binding
      protein 1 is crucial for the speck-like particle formation that represents
      activated inflammasomes.

PMID- 22869554
TI  - Peptidomics of three Bothrops snake venoms: insights into the molecular
      diversification of proteomes and peptidomes.
AB  - Snake venom proteomes/peptidomes are highly complex and maintenance of their
      integrity within the gland lumen is crucial for the expression of toxin
      activities. There has been considerable progress in the field of venom
      proteomics, however, peptidomics does not progress as fast, because of the lack
      of comprehensive venom sequence databases for analysis of MS data. Therefore, in
      many cases venom peptides have to be sequenced manually by MS/MS analysis or
      Edman degradation. This is critical for rare snake species, as is the case of
      Bothrops cotiara (BC) and B. fonsecai (BF), which are regarded as near threatened
      with extinction. In this study we conducted a comprehensive analysis of the venom
      peptidomes of BC, BF, and B. jararaca (BJ) using a combination of solid-phase
      extraction and reversed-phase HPLC to fractionate the peptides, followed by nano
      liquid chromatography-tandem MS (LC-MS/MS) or direct infusion electrospray
      ionization-(ESI)-MS/MS or MALDI-MS/MS analyses. We detected marked differences in
      the venom peptidomes and identified peptides ranging from 7 to 39 residues in
      length by de novo sequencing. Forty-four unique sequences were manually
      identified, out of which 30 are new peptides, including 17 bradykinin
      potentiating peptides, three poly-histidine-poly-glycine peptides and
      interestingly, 10 L-amino acid oxidase fragments. Some of the new bradykinin
      potentiating peptides display significant bradykinin potentiating activity.
      Automated database search revealed fragments from several toxins in the
      peptidomes, mainly from l-amino acid oxidase, and allowed the determination of
      the peptide bond specificity of proteinases and amino acid occurrences for the P4
      P4' sites. We also demonstrate that the venom lyophilization/resolubilization
      process greatly increases the complexity of the peptidome because of the
      imbalance caused to the venom proteome and the consequent activity of proteinases
      on venom components. The use of proteinase inhibitors clearly showed different
      outcomes in the peptidome characterization and suggested that degradomic
      peptidomic analysis of snake venoms is highly sensitive to the conditions of
      sampling procedures.

PMID- 22869555
TI  - Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells
      and abrogates suppression by T-regulatory cells.
AB  - Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders
      characterized by clonally derived and skin-homing malignant T cells that express
      high level of chemokine receptor CCR4, which is associated with their skin-homing
      capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can
      migrate to several different types of chemotactic ligand CCL17- and CCL22
      secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus,
      its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal
      target for antibody-based immunotherapy for CTCL and other types of solid tumors.
      Here, we conducted humanization and affinity optimization of a murine anti-CCR4
      monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and
      extracellular domains of CCR4 with high affinity and inhibits chemotaxis of
      CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent
      antitumor effect and in vitro mechanistic studies showed that both complement
      dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular
      cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK
      cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits
      chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression
      activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3,
      was selected for further preclinical development based on its higher binding
      affinity and more potent ADCC and CDC activities. Taken together, this high
      affinity humanized mAb2-3 with potent antitumor effect and a broad range of
      mechanisms of action may provide a novel immunotherapy for CTCL and other solid
      tumors.

PMID- 22869556
TI  - Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances
      invasiveness in pancreatic cancer cells.
AB  - Aberrant activation of Cyclin D-Cdk4/6 signaling pathway is commonly found in
      pancreatic ductal adenocarcinoma (PDAC). Here, we show that PD-0332991, a highly
      specific inhibitor for Cdk4 and Cdk6, exerted growth inhibitory effects on three
      human PDAC cell lines. Microarray analysis revealed that PD-0332991 downregulated
      cell-cycle-related genes, but upregulated genes implicated in extracellular
      matrix (ECM) remodeling and pancreatic cancer cell invasion and metastasis.
      Moreover, PD-0332991 enhanced invasion in TGF-beta-responsive PDAC cell lines
      that harbor a wild-type SMAD4 gene (COLO-357, PANC-1), but not in TGF-beta
      resistant AsPC-1 cells that harbor a mutated SMAD4. PD-0332991 also induced
      epithelial-mesenchymal transition (EMT) in COLO-357 and PANC-1, but not in AsPC-1
      cells. Inhibition of CDK4/6 using shRNA mimicked the effects of PD-0332991 on EMT
      induction. Furthermore, PD-0332991 increased Smad transcriptional activity in
      luciferase readout assays and activated TGF-beta signaling. SB-505124, an
      inhibitor of the type-I TGF-beta receptor (TbetaRI) kinase, completely blocked
      EMT induction by PD-0332991. When combined with PD-0332991, SB-505124 inhibited
      the growth of COLO-357 and PANC-1 cells. Taken together, these data suggest that
      anti-Cdk4/6 therapy could induce EMT and enhance pancreatic cancer cell invasion
      by activating Smad-dependent TGF-beta signaling, and that combining PD-0332991
      and SB-505124 may represent a novel therapeutic strategy in PDAC.

PMID- 22869557
TI  - A locked, dimeric CXCL12 variant effectively inhibits pulmonary metastasis of
      CXCR4-expressing melanoma cells due to enhanced serum stability.
AB  - The CXC chemokine receptor-4 (CXCR4) plays a critical role in cancer by
      positively regulating cancer cell metastasis and survival. We previously showed
      that high concentrations of the CXCR4 ligand, wild-type CXCL12 (wtCXCL12), could
      inhibit colorectal cancer metastasis in vivo, and we have hypothesized that
      wtCXCL12 dimerizes at high concentration to become a potent antagonist of CXCR4.
      To address this hypothesis, we engineered a covalently locked, dimeric variant of
      CXCL12 (CXCL122). Herein, we show that CXCL122 can not only inhibit implantation
      of lung metastasis of CXCR4-B16-F10 melanoma cells more effectively than AMD3100,
      but that CXCL122 also blocks the growth of established pulmonary tumors. To
      identify a basis for the in vivo efficacy of CXCL122, we conducted Western blot
      analysis and ELISA analyses, which revealed that CXCL122 was stable for at least
      12 hours in serum, whereas wtCXCL12 was quickly degraded. CXCL122 also maintained
      its antagonist properties in in vitro chemotaxis assays for up to 24 hours in
      serum, whereas wtCXCL12 was ineffective after 6 hours. Heat-inactivation of serum
      prolonged the stability and function of wtCXCL12 by more than 6 hours, suggesting
      enzymatic degradation as a possible mechanism for wtCXCL12 inactivation. In vitro
      analysis of amino-terminal cleavage by enzymes dipeptidylpeptidase IV
      (DPPIV/CD26) and matrix metalloproteinase-2 (MMP-2) resulted in 25-fold and 2
      fold slower degradation rates, respectively, of CXCL122 compared with wtCXCL12.
      In summary, our results suggest CXCL122 possesses greater potential as an
      antimetastatic drug as compared with AMD3100 or wtCXCL12, potentially due to
      enhanced serum stability in the presence of N-terminal degrading enzymes.

PMID- 22869558
TI  - Is germline transmission of MAD2 gene deletion associated with human fetal loss?
AB  - The spindle assembly checkpoint (SAC) monitors proper attachment of spindles to
      the kinetochore during mitotic and meiotic cell divisions and thus prevents
      aneuploidy. Chromosomal aneuploidy has been found to be associated with pregnancy
      loss and birth defects. Mad2 is one of the critical molecules of SAC. Deregulated
      Mad2 expression has been found to be associated with defective SAC-mediated
      abnormal meiotic progression in cell studies using animal models. Whether
      mutation in MAD2L1 is associated with the loss of Mad2 expression in aborted
      human fetuses is unknown. In this study, a correlation between aneuploidy and
      MAD2 defect was examined in primary fibroblast cultures obtained from abortuses.
      We report three trisomic abortuses with undetectable Mad2 expression. Further,
      quantitative real-time PCR revealed copy number deletion of MAD2 gene in these
      fetuses. Analysis of parental DNA samples available from two families revealed
      copy number loss of the same gene, suggesting Mendelian inheritance of MAD2
      deletion. This germline transmission of exonic deletion of MAD2 is possibly
      associated with its loss of expression resulting in abnormal SAC function,
      subsequent aneuploidy and pregnancy loss.

PMID- 22869559
TI  - Isolation and quantitation of topoisomerase complexes accumulated on Escherichia
      coli chromosomal DNA.
AB  - DNA topoisomerases are important targets in anticancer and antibacterial therapy
      because drugs can initiate cell death by stabilizing the transient covalent
      topoisomerase-DNA complex. In this study, we employed a method that uses CsCl
      density gradient centrifugation to separate unbound from DNA-bound GyrA/ParC in
      Escherichia coli cell lysates after quinolone treatment, allowing antibody
      detection and quantitation of the covalent complexes on slot blots. Using these
      procedures modified from the in vivo complexes of enzyme (ICE) bioassay, we found
      a correlation between gyrase-DNA complex formation and DNA replication inhibition
      at bacteriostatic (1* MIC) norfloxacin concentrations. Quantitation of the number
      of gyrase-DNA complexes per E. coli cell permitted an association between cell
      death and chromosomal gyrase-DNA complex accumulation at norfloxacin
      concentrations greater than 1* MIC. When comparing levels of gyrase-DNA complexes
      to topoisomerase IV-DNA complexes in the absence of drug, we observed that the
      gyrase-DNA complex level was higher (~150-fold) than that of the topoisomerase IV
      DNA complex. In addition, levels of gyrase and topoisomerase IV complexes reached
      a significant increase after 30 min of treatment at 1* and 1.7* MIC,
      respectively. These results are in agreement with gyrase being the primary target
      for quinolones in E. coli. We further validated the utility of this method for
      the study of topoisomerase-drug interactions in bacteria by showing the gyrase
      covalent complex reversibility after removal of the drug from the medium, and the
      resistant effect of the Ser83Leu gyrA mutation on accumulation of gyrase covalent
      complexes on chromosomal DNA.

PMID- 22869560
TI  - Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected
      patients.
AB  - The aim of this open-label, fixed-sequence study was to investigate the potential
      of the botanical supplement Echinacea purpurea to interact with etravirine, a
      nonnucleoside reverse transcriptase inhibitor of HIV. Fifteen HIV-infected
      patients receiving antiretroviral therapy with etravirine (400 mg once daily) for
      at least 4 weeks were included. E. purpurea root/extract-containing capsules were
      added to the antiretroviral treatment (500 mg every 8 h) for 14 days. Etravirine
      concentrations in plasma were determined by high-performance liquid
      chromatography immediately before and 1, 2, 4, 6, 8, 10, 12, and 24 h after a
      morning dose of etravirine on day 0 and etravirine plus E. purpurea on day 14.
      Individual etravirine pharmacokinetic parameters were calculated by
      noncompartmental analysis and compared between days 0 and 14 by means of the
      geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age
      was 46 years (interquartile range, 41 to 50), and the median body weight was 76
      kg (interquartile range, 68 to 92). Echinacea was well tolerated, and all
      participants completed the study. The GMR for etravirine coadministered with E.
      purpurea relative to etravirine alone was 1.07 (90% CI, 0.81 to 1.42) for the
      maximum concentration, 1.04 (90% CI, 0.79 to 1.38) for the area under the
      concentration-time curve from 0 to 24 h, and 1.04 (90% CI, 0.74 to 1.44) for the
      concentration at the end of the dosing interval. In conclusion, the
      coadministration of E. purpurea with etravirine was safe and well tolerated in
      HIV-infected patients; our data suggest that no dose adjustment for etravirine is
      necessary.

PMID- 22869561
TI  - gamma-glutamyl Spermine Synthetase PauA2 as a potential target of antibiotic
      development against Pseudomonas aeruginosa.
AB  - Polyamines are absolute requirements for cell growth. When in excess, Pseudomonas
      aeruginosa possesses six gamma-glutamylpolyamine synthetases (GPSs) encoded by
      the pauA1-pauA7 genes to initiate polyamine catabolism. Recently, the pauA2
      mutant was reported to lose the capability to grow on spermine (Spm) and
      spermidine (Spd) as sole carbon and nitrogen sources. Although this mutant grew
      normally in defined minimal medium and LB broth, growth was completely abolished
      by the addition of Spm or Spd. These two compounds exert a bactericidal effect
      (Spm > Spd) on the mutants as demonstrated by MIC measurements (over 500-fold
      reduction) and time-killing curves. Spm toxicity in the pauA2 mutant was
      attenuated when the major uptake system was further deleted from the strain,
      suggesting cytoplasmic targets of toxicity. In addition, the synergistic effect
      of Spm and carbenicillin in the wild-type strain PAO1 was diminished in mutants
      without functional PauA2. Furthermore, Spm MIC was reduced by 8-fold when the Spm
      uptake system was deleted from the wild-type strain, suggesting a second target
      of Spm toxicity in the periplasm. Experiments were also conducted to test the
      hypothesis that native Spm and Spd in human serum may be sufficient to kill the
      pauA2 mutant. Growth of the mutant was completely inhibited by 40% (vol/vol)
      human serum, whereas the parental strain required 80%. Colony counts indicated
      that the mutant but not the parent was in fact killed by human plasma. In
      addition, carbenicillin MIC against the mutant was reduced by 16-fold in the
      presence of 20% human serum while that of the parental strain remained unchanged.
      Taking PauA2 as the template, sequence comparison indicates that putative PauA2
      homologues are widespread in a variety of Gram-negative bacteria. In summary,
      this study reveals the importance of GPS in alleviation of polyamine toxicity
      when in excess, and it provides strong support to the feasibility of GPS as a
      molecular target for new antibiotic development.

PMID- 22869562
TI  - Characterization of resistance to the protease inhibitor GS-9451 in hepatitis C
      virus-infected patients.
AB  - GS-9451, a novel hepatitis C virus (HCV) nonstructural 3/4a (NS3/4a) protease
      inhibitor, is highly active in patients infected with HCV genotype 1 (GT 1). The
      aim of this study is to characterize the clinical resistance profile of GS-9451
      in GT 1 HCV-infected patients in a phase 1, 3-day monotherapy study. The full
      length NS3/4A gene was population sequenced at baseline, on the final treatment
      day, and at follow-up time points. NS3 protease domains from patient isolates
      with emerging mutations were cloned into an NS3 shuttle vector, and their
      susceptibilities to GS-9451 and other HCV inhibitors were determined using a
      transient replication assay. No resistance mutations at NS3 position 155, 156, or
      168 were detected in any of the baseline samples or in viruses from patients
      treated with 60 mg of GS-9451 once daily. Among patients who received 200 mg and
      400 mg of GS-9451, viruses with mutations at position D168 (D168E/G/V) and R155
      (R155K), which confer high-level resistance to GS-9451, were detected in those
      with GT 1b and GT 1a virus, respectively. Viruses with D168 mutations were no
      longer detected in any GT 1b patient at day 14 and subsequent time points. In GT
      1a patients, R155K mutants were replaced by the wild type in 57% of patients at
      week 24. These NS3 clinical mutants were sensitive to NS5B and NS5A inhibitors,
      as well as alpha interferon (IFN-alpha) and ribavirin. The lack of cross
      resistance between GS-9451 and other classes of HCV inhibitors supports the
      utility of combination therapy.

PMID- 22869563
TI  - In vitro pharmacokinetic/pharmacodynamic modeling of voriconazole activity
      against Aspergillus species in a new in vitro dynamic model.
AB  - The pharmacodynamics (PD) of voriconazole activity against Aspergillus spp. were
      studied using a new in vitro dynamic model simulating voriconazole human
      pharmacokinetics (PK), and the PK-PD data were bridged with human drug exposure
      to assess the percent target (near-maximum activity) attainment of different
      voriconazole dosages. Three Aspergillus clinical isolates (1 A. fumigatus, 1 A.
      flavus, and 1 A. terreus isolate) with CLSI MICs of 0.5 mg/liter were tested in
      an in vitro model simulating voriconazole PK in human plasma with C(max) values
      of 7, 3.5, and 1.75 mg/liter and a t(1/2) of 6 h. The area under the
      galactomannan index-time curve (AUC(GI)) was used as the PD parameter. In vitro
      PK-PD data were bridged with population human PK of voriconazole exposure, and
      the percent target attainment was calculated. The in vitro PK-PD relationship of
      fAUC(0-24)-AUC(GI) followed a sigmoid pattern (global R(2) = 0.97), with near
      maximum activities (10% fungal growth) observed at an fAUC(0-24) (95% confidence
      interval [CI]) of 18.9 (14.4 to 23.1) mg . h/liter against A. fumigatus, 26.6
      (21.1 to 32.9) mg . h/liter against A. flavus, and 36.2 (27.8 to 45.7) mg .
      h/liter against A. terreus (F test; P < 0.0001). Target attainment for 3, 4, and
      5 mg/kg-of-body-weight voriconazole dosages was 24% (11 to 45%), 80% (32 to 97%),
      and 93% (86 to 97%) for A. fumigatus, 12% (5 to 26%), 63% (17 to 93%), and 86%
      (73 to 94%) for A. flavus, and 4% (2 to 11%), 36% (6 to 83%), and 68% (47 to 83%)
      for A. terreus. Based on the in vitro exposure-effect relationships, a standard
      dosage of voriconazole may be adequate for most patients with A. fumigatus but
      not A. flavus and A. terreus infections, for which a higher drug exposure may be
      required. This could be achieved using a higher voriconazole dosage, thus
      highlighting the usefulness of therapeutic drug monitoring in patients receiving
      a standard dosage.

PMID- 22869564
TI  - Addition of ceftaroline to daptomycin after emergence of daptomycin
      nonsusceptible Staphylococcus aureus during therapy improves antibacterial
      activity.
AB  - Antistaphylococcal beta-lactams enhance daptomycin activity and have been used
      successfully in combination for refractory methicillin-resistant Staphylococcus
      aureus (MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown
      if it improves the daptomycin potency comparably to other beta-lactams. We report
      a complex patient case of endocarditis who was treated with daptomycin in
      combination with ceftaroline, which resulted in clearance of a daptomycin
      nonsusceptible strain. An in vitro pharmacokinetic/pharmacodynamic model of renal
      failure was used to simulate the development of daptomycin resistance and
      evaluate the microbiologic effects of daptomycin plus ceftaroline treatment.
      Combination therapy with daptomycin and ceftaroline restored daptomycin
      sensitivity in vivo and resulted in clearance of persistent blood cultures.
      Daptomycin susceptibility in vitro was increased in the presence of either
      ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was
      bactericidal in the model but resulted in regrowth and daptomycin resistance
      (MIC, 2 to 4 MUg/ml) with continued monotherapy. The addition of ceftaroline at
      200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial
      killing. Importantly, daptomycin plus ceftaroline as the initial combination
      therapy produced rapid and sustained bactericidal activity and prevented
      daptomycin resistance. Both in vivo- and in vitro-derived daptomycin resistance
      resulted in bacteria with more fluid cell membranes. After ceftaroline was added
      in the model, fluidity was restored to the level of the initial in vivo isolate.
      Daptomycin-resistant isolates required high daptomycin exposures (at least 10
      mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline
      combined with daptomycin was effective in eliminating daptomycin-resistant MRSA,
      and these results further justify the potential use of daptomycin plus beta
      lactam therapy for these refractory infections.

PMID- 22869565
TI  - Antiparasitic Effect of Vitamin B12 on Trypanosoma cruzi.
AB  - A nutritional characteristic of trypanosomatid protozoa is that they need a heme
      compound as a growth factor. Because of the cytotoxic activity of heme and its
      structural similarity to cobalamins, we have investigated the in vitro and in
      vivo effect of vitamin B(12) (or cyanocobalamin) on the different forms of
      Trypanosoma cruzi. Cyanocobalamin showed a marked antiparasitic activity against
      epimastigotes (50% inhibitory concentration [IC(50)], 2.42 MUM), amastigotes
      (IC(50), 10.69 MUM), and trypomastigotes (IC(50), 9.46 MUM). Anti-epimastigote
      and -trypomastigote values were 1.7 to 4 times lower than those obtained with the
      reference drug benznidazole (Bnz). We also found that B(12) and hemin do not
      interact with each other in their modes of action. Our results show that B(12)
      increases intracellular oxidative activity and stimulates both superoxide
      dismutase (50%) and ascorbate peroxidase (20%) activities, while the activity of
      trypanothione reductase was not modified. In addition, we found that the
      antioxidants dithiothreitol and ascorbic acid increase the susceptibility of the
      parasite to the cytotoxic action of B(12). We propose that vitamin B(12) exerts
      its growth-inhibitory effect through the generation of reactive oxygen species.
      In an in vivo assay, a significant reduction in the number of circulating
      parasites was found in T. cruzi-infected mice treated with cyanocobalamin and
      ascorbic acid. The reduction of parasitemia in benznidazole-treated mice was
      improved by the addition of these vitamins. According to our results, a
      combination of B(12) and Bnz should be further investigated due to its potential
      as a new therapeutic modality for the treatment of Chagas' disease.

PMID- 22869566
TI  - Population pharmacokinetics of conventional and intermittent dosing of liposomal
      amphotericin B in adults: a first critical step for rational design of innovative
      regimens.
AB  - There is increased interest in intermittent regimen of liposomal amphotericin B,
      which may facilitate use in ambulatory settings. Little is known, however, about
      the most appropriate dosage and schedule of administration. Plasma
      pharmacokinetic data were acquired from 30 patients receiving liposomal
      amphotericin B for empirical treatment of suspected invasive fungal infection.
      Two cohorts were studied. The first cohort received 3 mg of liposomal
      amphotericin B/kg of body weight/day; the second cohort received 10 mg of
      liposomal amphotericin B/kg at time zero, followed by 5 mg/kg at 48 and 120 h.
      The levels of liposomal amphotericin B were measured by high-pressure liquid
      chromatography (HPLC). The pharmacokinetics were estimated by using a population
      methodology. Monte Carlo simulations were performed. D-optimal design was used to
      identify maximally informative sampling times for both conventional and
      intermittent regimens for future studies. A three-compartment pharmacokinetic
      model best described the data. The pharmacokinetics for both conventional and
      intermittent dosing were linear. The estimates for the mean (standard deviation)
      for clearance and the volume of the central compartment were 1.60 (0.85) liter/h
      and 20.61 (15.27) liters, respectively. Monte Carlo simulations demonstrated
      considerable variability in drug exposure. Bayesian estimates for clearance and
      volume increased in a linear manner with weight, but only the former was
      statistically significant (P = 0.039). D-optimal design provided maximally
      informative sampling times for future pharmacokinetic studies. The
      pharmacokinetics of a conventional and an intermittently administered high-dose
      regimen liposomal amphotericin B are linear. Further pharmacokinetic
      pharmacodynamic preclinical and clinical studies are required to identify safe
      and effective intermittent regimens.

PMID- 22869567
TI  - Mutation in the Plasmodium falciparum CRT protein determines the stereospecific
      activity of antimalarial cinchona alkaloids.
AB  - The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer
      pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is
      greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum
      malaria parasites. They may act by the inhibition of heme crystallization within
      the parasite digestive vacuole in a manner similar to chloroquine. Earlier
      studies showed that a K76I mutation in the digestive vacuole-associated protein,
      PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal
      potency order of quinine and quinidine toward P. falciparum. To further explore
      PfCRT-alkaloid interactions in the malaria parasite, we measured the in vitro
      susceptibility of eight clonal lines of P. falciparum derived from the 106/1
      strain, each containing a unique pfcrt allele, to four Cinchona stereoisomer
      pairs: quinine and quinidine; cinchonidine and cinchonine; hydroquinine and
      hydroquinidine; 9-epiquinine and 9-epiquinidine. Stereospecific potency of the
      Cinchona alkaloids was associated with changes in charge and hydrophobicity of
      mutable PfCRT amino acids. In isogenic chloroquine-resistant lines, the IC(50)
      ratio of (-)/(+) CA pairs correlated with side chain hydrophobicity of the
      position 76 residue. Second-site PfCRT mutations negated the K76I stereospecific
      effects: charge-change mutations C72R or Q352K/R restored potency patterns
      similar to the parent K76 line, while V369F increased susceptibility to the
      alkaloids and nullified stereospecific differences between alkaloid pairs.
      Interactions between key residues of the PfCRT channel/transporter with (-) and
      (+) alkaloids are stereospecifically determined, suggesting that PfCRT binding
      plays an important role in the antimalarial activity of quinine and other
      Cinchona alkaloids.

PMID- 22869568
TI  - Identification of a novel genomic island conferring resistance to multiple
      aminoglycoside antibiotics in Campylobacter coli.
AB  - Historically, the incidence of gentamicin resistance in Campylobacter has been
      very low, but recent studies reported a high prevalence of gentamicin-resistant
      Campylobacter isolated from food-producing animals in China. The reason for the
      high prevalence was unknown and was addressed in this study. PCR screening
      identified aminoglycoside resistance genes aphA-3 and aphA-7 and the aadE-sat4
      aphA-3 cluster among 41 Campylobacter isolates from broiler chickens.
      Importantly, a novel genomic island carrying multiple aminoglycoside resistance
      genes was identified in 26 aminoglycoside resistant Campylobacter coli strains.
      Sequence analysis revealed that the genomic island was inserted between cadF and
      COO1582 on the C. coli chromosome and consists of 14 open reading frames (ORFs),
      including 6 genes (the aadE-sat4-aphA-3 cluster, aacA-aphD, aac, and aadE)
      encoding aminoglycoside-modifying enzymes. Analysis by pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing indicated that the C. coli
      isolates carrying this unique genomic island were clonal, and the clone of PFGE
      subtype III and sequence type (ST) 1625 was particularly predominant among the C.
      coli isolates examined, suggesting that clonal expansion may be involved in
      dissemination of this resistance island. Additionally, we were able to transfer
      this genomic island from C. coli to a Campylobacter jejuni strain using natural
      transformation under laboratory conditions, and the transfer resulted in a
      drastic increase in aminoglycoside resistance in the recipient strain. These
      findings identify a previously undescribed genomic island that confers resistance
      to multiple aminoglycoside antibiotics. Since aminoglycoside antibiotics are used
      for treating occasional systemic infections caused by Campylobacter, the
      emergence and spread of this antibiotic resistance genomic island represent a
      potential concern for public health.

PMID- 22869569
TI  - DNA microarray profiling of a diverse collection of nosocomial methicillin
      resistant staphylococcus aureus isolates assigns the majority to the correct
      sequence type and staphylococcal cassette chromosome mec (SCCmec) type and
      results in the subsequent identification and characterization of novel SCCmec
      SCCM1 composite islands.
AB  - One hundred seventy-five isolates representative of methicillin-resistant
      Staphylococcus aureus (MRSA) clones that predominated in Irish hospitals between
      1971 and 2004 and that previously underwent multilocus sequence typing (MLST) and
      staphylococcal cassette chromosome mec (SCCmec) typing were characterized by spa
      typing (175 isolates) and DNA microarray profiling (107 isolates). The isolates
      belonged to 26 sequence type (ST)-SCCmec types and subtypes and 35 spa types. The
      array assigned all isolates to the correct MLST clonal complex (CC), and 94%
      (100/107) were assigned an ST, with 98% (98/100) correlating with MLST. The array
      assigned all isolates to the correct SCCmec type, but subtyping of only some
      SCCmec elements was possible. Additional SCCmec/SCC genes or DNA sequence
      variation not detected by SCCmec typing was detected by array profiling,
      including the SCC-fusidic acid resistance determinant Q6GD50/fusC. Novel
      SCCmec/SCC composite islands (CIs) were detected among CC8 isolates and comprised
      SCCmec IIA-IIE, IVE, IVF, or IVg and a ccrAB4-SCC element with 99% DNA sequence
      identity to SCC(M1) from ST8/t024-MRSA, SCCmec VIII, and SCC-CI in Staphylococcus
      epidermidis. The array showed that the majority of isolates harbored one or more
      superantigen (94%; 100/107) and immune evasion cluster (91%; 97/107) genes. Apart
      from fusidic acid and trimethoprim resistance, the correlation between isolate
      antimicrobial resistance phenotype and the presence of specific resistance genes
      was >=97%. Array profiling allowed high-throughput, accurate assignment of MRSA
      to CCs/STs and SCCmec types and provided further evidence of the diversity of
      SCCmec/SCC. In most cases, array profiling can accurately predict the resistance
      phenotype of an isolate.

PMID- 22869570
TI  - Pyrazinamide may improve fluoroquinolone-based treatment of multidrug-resistant
      tuberculosis.
AB  - The role of pyrazinamide in the current treatment of multidrug-resistant (MDR)
      tuberculosis (TB) is uncertain. From a territory-wide registry of MDR-TB cases
      diagnosed between 1995 and 2009, we assembled a cohort of 194 patients with MDR
      pulmonary TB given fluoroquinolone-containing regimens. Stratified by
      pyrazinamide use and susceptibility, there were 83 users with pyrazinamide
      susceptible MDR-TB (subgroup A), 24 users with pyrazinamide-resistant MDR-TB
      (subgroup B), 40 nonusers with pyrazinamide-susceptible MDR-TB (subgroup C), and
      47 nonusers with pyrazinamide-resistant MDR-TB (subgroup D). We estimated the
      adjusted risk ratio (ARR) of early sputum culture conversion (ARR-culture) that
      occurred within 90 days posttreatment and that of cure or treatment completion
      (ARR-success) that occurred by 2 years posttreatment due to pyrazinamide use with
      susceptibility. In comparison with subgroup B, ARR-culture and ARR-success were
      1.38 (95% confidence interval [CI], 0.89 to 2.12) and 1.38 (95% confidence
      interval [CI], 0.88 to 2.17), respectively. Corresponding findings were 0.99 (95%
      CI, 0.81 to 1.22) and 0.99 (95% CI, 0.78 to 1.26) in comparison with subgroup C
      and 1.09 (95% CI, 0.84 to 1.42) and 0.94 (95% CI, 0.74 to 1.20) in comparison
      with subgroup D. Early culture conversion significantly increased the incidence
      proportion of cure or treatment completion by 71% (95% CI, 26% to 133%).
      Selection bias among pyrazinamide nonusers might have underestimated the role of
      pyrazinamide. Comparison of pyrazinamide users showed that pyrazinamide increased
      the incidence proportion of early culture conversion and that of cure or
      treatment completion by a best estimate of 38% for both. This magnitude of change
      exceeded the 15 to 20% increase in the 2-month culture conversion rate of drug
      susceptible TB that results from adding pyrazinamide to isoniazid and rifampin.
      Pyrazinamide is likely important in fluoroquinolone-based treatment of MDR-TB.

PMID- 22869571
TI  - TD-1792 versus vancomycin for treatment of complicated skin and skin structure
      infections.
AB  - TD-1792 is a first-in-class glycopeptide-cephalosporin heterodimer that exhibits
      bactericidal activity against Gram-positive pathogens. We conducted a randomized,
      double-blind, active-control, phase II trial in patients with complicated skin
      and skin structure infections caused by suspected or confirmed Gram-positive
      organisms. Patients 18 to 65 years old were randomized to receive 7 to 14 days of
      either TD-1792 (2 mg/kg of body weight intravenously [i.v.] every 24 h [q24h]) or
      vancomycin (1 g i.v. q12h, with dosage regimens adjusted per site-specific
      procedures). A total of 197 patients were randomized and received at least one
      dose of study medication. Rates of clinical success at the test-of-cure
      evaluation were similar in all analysis populations. Among 170 clinically
      evaluable patients, cure rates were 91.7% and 90.7% in the TD-1792 and vancomycin
      groups, respectively (95% confidence interval [CI] of -7.9 to 9.7 for the
      difference). In microbiologically evaluable patients with methicillin-resistant
      Staphylococcus aureus at baseline (n = 75), cure rates were 94.7% in the TD-1792
      group and 91.9% in the vancomycin group. Microbiological eradication of Gram
      positive pathogens (n = 126) was achieved in 93.7% and 92.1% of patients in the
      TD-1792 and vancomycin groups, respectively. Seven patients were discontinued
      from study medication due to an adverse event (AE): 2 and 5 in the TD-1792 and
      vancomycin groups, respectively. AEs were of similar types and severities between
      the two groups, other than pruritus, which was more common in patients who
      received vancomycin. No patients in the TD-1792 group experienced a serious AE.
      This study supports further clinical development of TD-1792 in patients with Gram
      positive infection.

PMID- 22869572
TI  - Efficient replication of genotype 3a and 4a hepatitis C virus replicons in human
      hepatoma cells.
AB  - Despite recent advances in the treatment of hepatitis C, the quest for pan
      genotype, effective, and well-tolerated inhibitors continues. To facilitate these
      efforts, it is desirable to have in vitro replication systems for all major HCV
      genotypes. However, cell culture replication systems exist for only genotypes 1a,
      1b, and 2a. In this study, we generated G418-selectable subgenomic replicons for
      prototype strains of genotypes 3a (S52) and 4a (ED43). Production of G418
      resistant colonies by S52 and ED43 in Huh-7.5 cells required the amino acid
      substitutions S2210I and R2882G, respectively, cell culture adaptive mutations
      originally reported for genotype 1b replicons. RNA replication was confirmed by
      quantitative reverse transcription-PCR and detection of viral protein. Sequencing
      of multiple independent replicon clones revealed the presence of additional
      nonsynonymous mutations. Interestingly, all potentially adaptive mutations mapped
      to the NS3 protein. These mutations, when introduced back into original
      constructs, substantially increased colony formation efficiency. To make these
      replicons useful for high-throughput screening and evaluation of antiviral
      compounds, they were modified to express a chimeric fusion protein of firefly
      luciferase and neomycin phosphotransferase to yield stable replicon-expressing
      cells. Using these constructs, the inhibitory effects of beta interferon (IFN
      beta), an NS3 protease inhibitor, and an NS5B nucleoside polymerase inhibitor
      were readily detected by monitoring luciferase activity. In conclusion, we have
      established functional replicons for HCV genotypes 3a and 4a, important new
      additions to the armamentarium required to develop inhibitors with a pan-genotype
      activity.

PMID- 22869573
TI  - In vitro and in vivo activities of the novel Ketolide RBx 14255 against
      Clostridium difficile.
AB  - The MIC(90) of RBx 14255, a novel ketolide, against Clostridium difficile was 4
      MUg/ml (MIC range, 0.125 to 8 MUg/ml), and this drug was found to be more potent
      than comparator drugs. An in vitro time-kill kinetics study of RBx 14255 showed
      time-dependent bacterial killing for C. difficile. Furthermore, in the hamster
      model of C. difficile infection, RBx 14255 demonstrated greater efficacy than
      metronidazole and vancomycin, making it a promising candidate for C. difficile
      treatment.

PMID- 22869574
TI  - Corifungin, a new drug lead against Naegleria, identified from a high-throughput
      screen.
AB  - Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by
      the free-living ameba Naegleria fowleri. The drug of choice in treating PAM is
      the antifungal antibiotic amphotericin B, but its use is associated with severe
      adverse effects. Moreover, few patients treated with amphotericin B have survived
      PAM. Therefore, fast-acting and efficient drugs are urgently needed for the
      treatment of PAM. To facilitate drug screening for this pathogen, an automated,
      high-throughput screening methodology was developed and validated for the closely
      related species Naegleria gruberi. Five kinase inhibitors and an NF-kappaB
      inhibitor were hits identified in primary screens of three compound libraries.
      Most importantly for a preclinical drug discovery pipeline, we identified
      corifungin, a water-soluble polyene macrolide with a higher activity against
      Naegleria than that of amphotericin B. Transmission electron microscopy of N.
      fowleri trophozoites incubated with different concentrations of corifungin showed
      disruption of cytoplasmic and plasma membranes and alterations in mitochondria,
      followed by complete lysis of amebae. In vivo efficacy of corifungin in a mouse
      model of PAM was confirmed by an absence of detectable amebae in the brain and
      100% survival of mice for 17 days postinfection for a single daily
      intraperitoneal dose of 9 mg/kg of body weight given for 10 days. The same dose
      of amphotericin B did not reduce ameba growth, and mouse survival was
      compromised. Based on these results, the U.S. FDA has approved orphan drug status
      for corifungin for the treatment of PAM.

PMID- 22869575
TI  - Guidelines for reporting novel mecA gene homologues.

PMID- 22869576
TI  - Characterization of hepatitis C virus (HCV) quasispecies dynamics upon short-term
      dual therapy with the HCV NS5B nucleoside polymerase inhibitor mericitabine and
      the NS3/4 protease inhibitor danoprevir.
AB  - In the INFORM-1 study, 73 patients with chronic hepatitis C virus infection
      received mericitabine plus danoprevir for up to 13 days. Seventy-two patients
      experienced a continuous decline in HCV RNA levels during treatment, and of these
      patients, 14 had viral loads that remained >1,000 IU/ml by day 13 and 1 met the
      definition for viral breakthrough. In-depth NS5B and NS3/4A population and clonal
      sequencing studies and mericitabine and danoprevir drug susceptibility testing
      were performed to assess the variability and quasispecies dynamics before and
      upon monotherapy or dual therapy. Sequence analysis of the viral quasispecies
      indicated that the mericitabine resistance mutation S282T was not present at
      baseline, nor was it selected (even at a low level) during treatment. Protease
      inhibitor resistance mutations, either as predominant or as minority species,
      were detected in 18 patients at baseline. No enrichment of minority protease
      inhibitor-resistant variants present at baseline was observed during treatment;
      viral population samples were fully susceptible to mericitabine and/or
      danoprevir, despite the presence within their quasispecies of minority variants
      confirmed to have reduced susceptibility to danoprevir or other protease
      inhibitors. It was also observed that certain NS3 amino acid substitutions
      affected protease inhibitor drug susceptibility in a compound-specific manner and
      varied with the genetic context. In summary, the slower kinetics of viral load
      decline observed in some patients was not due to the selection of danoprevir or
      mericitabine resistance during treatment. Over 2 weeks' therapy, mericitabine
      suppressed the selection of danoprevir resistance, results that could differ upon
      longer treatment periods.

PMID- 22869577
TI  - Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease
      Inhibitor Asunaprevir (BMS-650032).
AB  - Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor
      that has demonstrated efficacy in patients chronically infected with HCV genotype
      1 when combined with alfa interferon and/or the NS5A replication complex
      inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex,
      with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing
      genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by
      the absence of any significant activity against the closely related GB virus-B
      NS3 protease and a panel of human serine or cysteine proteases. In cell culture,
      ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with
      50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker
      activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Selectivity was
      again demonstrated by the absence of activity (EC(50), >12 MUM) against a panel
      of other RNA viruses. ASV exhibited additive or synergistic activity in
      combination studies with alfa interferon, ribavirin, and/or inhibitors
      specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in
      several animal species indicated that ASV displayed a hepatotropic disposition
      (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four
      hours postdose, liver exposures across all species tested were >=110-fold above
      the inhibitor EC(50)s observed with HCV genotype-1 replicons. Based on these
      virologic and exposure properties, ASV holds promise for future utility in a
      combination with other anti-HCV agents in the treatment of HCV-infected patients.

PMID- 22869578
TI  - The liver partition coefficient-corrected inhibitory quotient and the
      pharmacokinetic-pharmacodynamic relationship of directly acting anti-hepatitis C
      virus agents in humans.
AB  - Pharmacokinetic-pharmacodynamic (PK-PD) data analyses from early hepatitis C
      virus (HCV) clinical trials failed to show a good correlation between the plasma
      inhibitory quotient (IQ) and antiviral activity of different classes of directly
      acting antiviral agents (DAAs). The present study explored whether use of the
      liver partition coefficient-corrected IQ (LCIQ) could improve the PK-PD
      relationship. Animal liver partition coefficients (Kp(liver)) were calculated
      from liver to plasma exposure ratios. In vitro hepatocyte partition coefficients
      (Kp(hep)) were determined by the ratio of cellular to medium drug concentrations.
      Human Kp(liver) was predicted using an in vitro-in vivo proportionality method:
      the species-averaged animal Kp(liver) multiplied by the ratio of human Kp(hep)
      over those in animals. LCIQ was calculated using the IQ multiplied by the
      predicted human Kp(liver). Our results demonstrated that the in vitro-in vivo
      proportionality approach provided the best human Kp(liver) prediction, with
      prediction errors of <45% for all 5 benchmark drugs evaluated (doxorubicin,
      verapamil, digoxin, quinidine, and imipramine). Plasma IQ values correlated
      poorly (r(2) of 0.48) with maximum viral load reduction and led to a
      corresponding 50% effective dose (ED(50)) IQ of 42, with a 95% confidence
      interval (CI) of 0.1 to 148534. In contrast, the LCIQ-maximum VLR relationship
      fit into a typical sigmoidal curve with an r(2) value of 0.95 and an ED(50) LCIQ
      of 121, with a 95% CI of 83 to 177. The present study provides a novel human
      Kp(liver) prediction model, and the LCIQ correlated well with the viral load
      reductions observed in short-term HCV monotherapy of different DAAs and provides
      a valuable tool to guide HCV drug discovery.

PMID- 22869579
TI  - Nevirapine exposure with WHO pediatric weight band dosing: enhanced therapeutic
      concentrations predicted based on extensive international pharmacokinetic
      experience.
AB  - Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used
      worldwide as part of combination antiretroviral therapy in infants and children
      to treat HIV infection. Dosing based on either weight or body surface area has
      been approved by the U.S. Food and Drug Administration (FDA) but can be difficult
      to implement in resource-limited settings. The World Health Organization (WHO)
      has developed simplified weight band dosing for NVP, but it has not been
      critically evaluated. NVP pharmacokinetic data were combined from eight pediatric
      clinical trials (Pediatric AIDS Clinical Trials Group [PACTG] studies 245, 356,
      366, 377, 403, 1056, and 1069 and Children with HIV in Africa Pharmacokinetics
      and Adherence of Simple Antiretroviral Regimens [CHAPAS]) representing subjects
      from multiple continents and across the pediatric age continuum. A population
      pharmacokinetic model was developed to characterize developmental changes in NVP
      disposition, identify potential sources of NVP pharmacokinetic variability, and
      assess various pediatric dosing strategies and their impact on NVP exposure. Age,
      CYP2B6 genotype, and ritonavir were independent predictors of oral NVP clearance.
      The Triomune fixed-dose tablet was an independent predictor of bioavailability
      compared to the liquid and other tablet formulations. Monte Carlo simulations of
      the final model were used to assess WHO weight band dosing recommendations. The
      final pharmacokinetic model indicated that WHO weight band dosing is likely to
      result in a percentage of children with NVP exposure within the target range
      similar to that obtained with FDA dosing. Weight band dosing of NVP proposed by
      the WHO has the potential to provide a simple and effective dosing strategy for
      resource limited settings.

PMID- 22869580
TI  - Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral
      osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin
      and trimethoprim-sulfamethoxazole.
AB  - We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin
      intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases
      complicated by bacteremia treated with high-dose daptomycin and trimethoprim
      sulfamethoxazole. Both patients responded rapidly and favorably to this
      combination. The clinical isolates from the two patients were tested post hoc in
      an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model to confirm the
      bactericidal activity and enhancement of daptomycin and trimethoprim
      sulfamethoxazole. The combination of high-dose daptomycin and trimethoprim
      sulfamethoxazole should be explored further for the treatment of DNS VISA
      strains.

PMID- 22869581
TI  - Pharmacokinetics and pharmacodynamics of oral artesunate monotherapy in patients
      with uncomplicated Plasmodium falciparum malaria in western Cambodia.
AB  - Artemisinin-resistant malaria along the Thailand-Cambodian border is an important
      public health concern, yet mechanisms of drug action and their contributions to
      the development of resistance are poorly understood. The pharmacokinetics and
      pharmacodynamics of oral artesunate monotherapy were explored in a dose-ranging
      trial in an area of emerging artesunate resistance in western Cambodia. We
      enrolled 143 evaluable subjects with uncomplicated Plasmodium falciparum malaria
      in an open label study of directly observed artesunate monotherapy at 3 dose
      levels (2, 4, and 6 mg/kg of body weight/day) for 7 days at Tasanh Health Center,
      Tasanh, Cambodia. Clinical outcomes were similar among the 3 groups. Wide
      variability in artesunate and dihydroartemisinin concentrations in plasma was
      observed. No significant dose-effect or concentration-effect relationships
      between pharmacokinetic (PK) and parasite clearance parameters were observed,
      though baseline parasitemia was modestly correlated with increased parasite
      clearance times. The overall parasite clearance times were prolonged compared
      with the clearance times in a previous study at this site in 2006 to 2007, but
      this did not persist when the evaluation was limited to subjects with a
      comparable artesunate dose (4 mg/kg/day) and baseline parasitemia from the two
      studies. Reduced plasma drug levels with higher presentation parasitemias,
      previously hypothesized to result from partitioning into infected red blood
      cells, was not observed in this population with uncomplicated malaria. Neither in
      vitro parasite susceptibility nor plasma drug concentrations appeared to have a
      direct relationship with the pharmacodynamic (PD) effects of oral artesunate on
      malaria parasites. While direct concentration-effect relationships were not
      found, it remains possible that a population PK modeling approach that allows
      modeling of greater dose separation might discern more-subtle relationships.

PMID- 22869582
TI  - Prohibitin attenuates colitis-associated tumorigenesis in mice by modulating p53
      and STAT3 apoptotic responses.
AB  - Although inflammatory bowel disease is associated with higher risk of colorectal
      cancer, the precise pathogenic mechanisms underlying this association are not
      completely understood. Prohibitin 1 (PHB), a protein implicated in the regulation
      of proliferation, apoptosis, and transcription, is decreased in intestinal
      inflammation. In this study, we have established a key function for PHB in
      mediating colitis-associated cancer. Wild-type and transgenic (Tg) mice
      specifically overexpressing PHB in intestinal epithelial cells were subjected to
      a classical two-stage protocol of colitis-associated carcinogenesis. In addition,
      wild-type and p53 null human cell models were used to assess PHB interaction with
      STAT3 and p53. Wild-type mice exhibited decreased mucosal PHB protein expression
      during colitis-associated carcinogenesis. Tg mice exhibited decreased
      susceptibility in a manner associated with increased apoptosis, p53, Bax, and Bad
      expression plus decreased Bcl-xL and Bcl-2 expression. PHB overexpression in wild
      type but not p53 null human cells increased expression of Bax, Bad, and caspase-3
      cleavage. In wild-type p53 cells, PHB overexpression decreased basal and
      interleukin-6-induced STAT3 activation and expression of the STAT3 responsive
      genes Bcl-xL and Bcl-2. PHB coimmunoprecipitated with phospho-STAT3 in addition
      to p53 in cultured cell lysates and colon mucosa. This is the first study to show
      interaction between PHB and STAT3 in vivo. In summary, our findings suggest that
      PHB protects against colitis-associated cancer by modulating p53- and STAT3
      mediated apoptosis. Modulation of PHB expression in intestinal epithelial cells
      may offer a potential therapeutic approach to prevent colitis-associated
      carcinogenesis.

PMID- 22869583
TI  - Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX
      occur in multiple myeloma with 8q24 abnormality.
AB  - Chromosome 8q24 rearrangements are occasionally found in multiple myeloma and are
      associated with tumor progression. The 8q24 rearrangements were detected by FISH
      in 12 of 54 patients with multiple myeloma (22.2%) and in 8 of 11 multiple
      myeloma cell lines (72.7%). The breakpoints of 8q24 in 10 patients with multiple
      myeloma and in all multiple myeloma cell lines were assigned to a 360 kb segment,
      which was divided into 4 regions: approximately 120 kb centromeric to MYC (5'
      side of MYC), the region centromerically adjacent to PVT1 (~ 170 kb region,
      including MYC, of 5' side of PVT1), the PVT1 region, and the telomeric region to
      PVT1. PVT1 rearrangements were most common and found in 7 of 12 patients (58.3%)
      and 5 of 8 cell lines (62.5%) with 8q24 abnormalities. A combination of spectral
      karyotyping (SKY), FISH, and oligonucleotide array identified several partner
      loci of PVT1 rearrangements, such as 4p16, 4q13, 13q13, 14q32, and 16q23-24. Two
      novel chimeric genes were identified: PVT1-NBEA in the AMU-MM1 cell line
      harboring t(8;13)(q24;q13) and PVT1-WWOX in RPMI8226 cell line harboring
      der(16)t(16;22)ins(16;8)(q23;q24). The PVT1-NBEA chimera in which PVT1 exon 1 was
      fused to NBEA exon 2 and the PVT1-WWOX in which PVT1 exon 1 was fused to WWOX
      exon 9 were associated with the expression of abnormal NBEA and WWOX lacking
      their N-terminus, respectively. These findings suggest that PVT1 rearrangements
      may represent a novel molecular paradigm underlying the pathology of 8q24
      rearrangement-positive multiple myeloma.

PMID- 22869584
TI  - Intravesical delivery of small activating RNA formulated into lipid nanoparticles
      inhibits orthotopic bladder tumor growth.
AB  - Practical methods for enhancing protein production in vivo remain a challenge.
      RNA activation (RNAa) is emerging as one potential solution by using double
      stranded RNA (dsRNA) to increase endogenous gene expression. This approach,
      although related to RNA interference (RNAi), facilitates a response opposite to
      gene silencing. Duplex dsP21-322 and its chemically modified variants are
      examples of RNAa-based drugs that inhibit cancer cell growth by inducing
      expression of tumor suppressor p21(WAF1/CIP1) (p21). In this study, we
      investigate the therapeutic potential of dsP21-322 in an orthotopic model of
      bladder cancer by formulating a 2'-fluoro-modified derivative (dsP21-322-2'F)
      into lipid nanoparticles (LNP) for intravesical delivery. LNP composition is
      based upon clinically relevant formulations used in RNAi-based therapies
      consisting of PEG-stabilized unilamellar liposomes built with lipid DLin-KC2-DMA.
      We confirm p21 induction, cell-cycle arrest, and apoptosis in vitro following
      treatment with LNP-formulated dsP21-322-2'F (LNP-dsP21-322-2'F) or one of its
      nonformulated variants. Both 2'-fluoro modification and LNP formulation also
      improve duplex stability in urine. Intravesical delivery of LNP-dsP21-322-2'F
      into mouse bladder results in urothelium uptake and extends survival of mice with
      established orthotopic human bladder cancer. LNP-dsP21-322-2'F treatment also
      facilitates p21 activation in vivo leading to regression/disappearance of tumors
      in 40% of the treated mice. Our results provide preclinical proof-of-concept for
      a novel method to treat bladder cancer by intravesical administration of LNP
      formulated RNA duplexes.

PMID- 22869585
TI  - Opposing roles for IL-23 and IL-12 in maintaining occult cancer in an equilibrium
      state.
AB  - Cancer immunoediting, the process by which the immune system controls tumor
      growth and shapes tumor immunogenicity, consists of 3 stages: elimination,
      equilibrium, and escape. The molecular mechanisms that underlie the equilibrium
      phase, during which the immune system maintains tumor dormancy, remain
      incompletely defined. Here, we investigated the length of the equilibrium phase
      during immune control of methylcholanthrene (MCA)-induced or p53 mutant cancers
      and showed the critical and opposing roles of interleukin (IL)-23 and IL-12 in
      maintaining cancer cells in a state of immune-mediated dormancy. Inhibition of IL
      23p19 was shown to reduce the malignant potential of lesions established by MCA
      inoculation, whereas inhibition of IL-12/23p40 enhanced tumor outgrowth.
      Furthermore, agonistic anti-CD40 antibody treatment mimicked the effects of anti
      IL-23p19 monoclonal antibody treatment. Other cytokines such as IL-4, IL-17, TNF,
      and IFNalphabeta, which are known to play important roles either in MCA
      tumorigenesis or in the elimination phase of cancer immunoediting, did not play
      critical roles in maintaining the equilibrium phase. Taken together, our findings
      show opposing roles for IL-23 and IL-12 in determining the outgrowth versus
      dormancy of occult neoplasia and suggest a potential long-term danger in using IL
      12/23p40 antibodies for treating human autoimmune inflammatory disorders.

PMID- 22869586
TI  - The Inter-Organizational Summit on Education and Training (ISET) 2010 survey on
      the influence of the Houston conference training guidelines.
AB  - A conference specific to the education and training of clinical neuropsychology
      was held in 1997, which led to a report published in the Archives of Clinical
      Neuropsychology (Hannay, J., Bieliauskas, L., Crosson, B., Hammeke, T., Hamsher,
      K., & Koffler, S. (1998). Proceedings of the Houston Conference on Specialty
      Education and Training in Clinical Neuropsychology. Archives of Clinical
      Neuropsychology, 13, 157-250.). The guidelines produced by this conference have
      been referred to as the Houston Conference (HC) guidelines. Since that time,
      there has been considerable discussion, and some disagreement, about whether the
      HC guidelines produced a positive outcome in the training of neuropsychologists.
      To explore this question and determine how widely the HC guidelines were
      implemented, a meeting was held in 2006. Present and past leaders of the American
      Psychological Association Division 40 (Clinical Neuropsychology), the National
      Academy of Neuropsychology, and the Association of Postdoctoral Programs in
      Clinical Neuropsychology met to discuss the possible need for an Inter
      Organizational Summit on Education and Training (ISET). A decision was reached to
      have the ISET Steering Committee conduct a survey of clinical neuropsychologists
      that could address the extent to which HC guidelines were present in the
      specialty and whether the influence of the HC guidelines was positive. An online
      survey was constructed, with data gathered in 2010. The current paper presents
      and discusses the ISET survey results. Specific findings need to be viewed
      cautiously due to the relatively low response rate. However, with some direct
      parallels to a larger recent survey of clinical neuropsychologists, the following
      general conclusions appear well founded: (a) the demographics of respondents in
      the ISET survey are comparable with a recent larger professional practice survey
      and thus may reasonably represent the specialty; (b) the HC guidelines appear to
      have been widely adopted by training programs, in that a large proportion of
      younger practitioners endorsed having had HC-adherent training; and (c) HC
      adherent training is associated with a higher frequency endorsement of being well
      prepared to engage in key professional activities subsequent to the completion of
      training when compared with those not having HC-adherent training. Overall, the
      ISET Steering Committee has concluded that the HC guidelines have been widely
      adopted and that trainees associate participation in HC-adherent training as
      advantageous. A potential revision based on unfavorable outcomes is deemed
      unnecessary. Nonetheless, the ISET Steering Committee recognizes that training
      needs change as a function of the broadening of our field and the introduction of
      related new technologies, which may prompt updates. The ISET Steering Committee
      supports the idea that periodic review and updating of training models is
      prudent.

PMID- 22869587
TI  - Chaperone heat shock protein 90 mobilization and hydralazine cytoprotection
      against acrolein-induced carbonyl stress.
AB  - Toxic carbonyls such as acrolein participate in many degenerative diseases.
      Although the nucleophilic vasodilatory drug hydralazine readily traps such
      species under "test-tube" conditions, whether these reactions adequately explain
      its efficacy in animal models of carbonyl-mediated disease is uncertain. We have
      previously shown that hydralazine attacks carbonyl-adducted proteins in an
      "adduct-trapping" reaction that appears to take precedence over direct "carbonyl
      sequestering" reactions, but how this reaction conferred cytoprotection was
      unclear. This study explored the possibility that by increasing the bulkiness of
      acrolein-adducted proteins, adduct-trapping might alter the redistribution of
      chaperones to damaged cytoskeletal proteins that are known targets for acrolein.
      Using A549 lung adenocarcinoma cells, the levels of chaperones heat shock protein
      (Hsp) 40, Hsp70, Hsp90, and Hsp110 were measured in intermediate filament
      extracts prepared after a 3-h exposure to acrolein. Exposure to acrolein alone
      modestly increased the levels of all four chaperones. Coexposure to hydralazine
      (10-100 MUM) strongly suppressed cell ATP loss while producing strong adduct
      trapping in intermediate filaments. Most strikingly, hydralazine selectively
      boosted the levels of cytoskeletal-associated Hsp90, including a high-mass
      species that was sensitive to the Hsp90 inhibitor 17-N-allylamino-17
      demethoxygeldanamycin. Biochemical fractionation of acrolein- and hydralazine
      treated cells revealed that hydralazine likely promoted Hsp90 migration from
      cytosol into other subcellular compartments. A role for Hsp90 mobilization in
      cytoprotection was confirmed by the finding that brief heat shock treatment
      suppressed acute acrolein toxicity in A549 cells. Taken together, these findings
      suggest that by increasing the steric bulk of carbonyl-adducted proteins, adduct
      trapping drugs trigger the intracellular mobilization of the key molecular
      chaperone Hsp90.

PMID- 22869588
TI  - Redox regulation by nuclear factor erythroid 2-related factor 2: gatekeeping for
      the basal and diabetes-induced expression of thioredoxin-interacting protein.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor
      activated by a range of oxidants and electrophiles. The transcriptional response
      to endogenous oxidative cues by Nrf2 plays an important role in mammalian redox
      physiology and oxidative pathology. Hyperglycemia induces oxidative stress in the
      heart where it leads to apoptosis and ultimately cardiomyopathy. Here we
      investigated the mechanism by which Nrf2 suppresses oxidative stress in diabetic
      mouse heart. Knockout (KO) of Nrf2 induced oxidative stress and apoptosis in KO
      heart; diabetes further increased oxidative damage. A pathway-focused gene array
      revealed that Nrf2 controls the expression of 24 genes in the heart, including
      the gene encoding thioredoxin-interacting protein (TXNIP). Nrf2 suppressed the
      basal expression of Txnip in the heart and blocked induction of Txnip by high
      glucose by binding to an antioxidant response element (ARE) (-1286 to -1276) of
      the Txnip promoter. Binding of Nrf2 to ARE also suppressed the binding of MondoA
      to the carbohydrate response element with or without high glucose. TXNIP promoted
      reactive oxygen species production and apoptosis by inhibiting thioredoxin. On
      the other hand, Nrf2 boosted thioredoxin activity by inhibiting Txnip. The
      findings revealed, for the first time, that Nrf2 is a key gatekeeper of Txnip
      transcription, suppressing both its basal expression and MondoA-driven induction
      to control the thioredoxin redox signaling in diabetes.

PMID- 22869589
TI  - Small molecule modulation of nuclear receptor conformational dynamics:
      implications for function and drug discovery.
AB  - Nuclear receptors are targets for a wide range of ligands, both natural and
      synthetic, that regulate their activity and provide a means to pharmacologically
      modulate the receptor. Recent emphasis in the nuclear receptor field has focused
      on selective nuclear receptor modulators, which can display graded
      transcriptional responses and tissue selective pharmacological responses that
      deviate from the prototypical agonist or antagonist. Understanding the molecular
      mechanism of action of these selective modulators will provide significant
      insight toward the development of the next generation of modulators. Although
      most nuclear receptor structural studies have primarily focused on obtaining
      ligand-receptor cocrystal structures, recent studies implicate an important role
      for protein dynamics in the mechanism of action of nuclear receptor ligands. Here
      we review nuclear receptor studies reporting how ligands modulate the
      conformational dynamics of the nuclear receptor ligand-binding domain (LBD). A
      particular emphasis is placed on protein NMR and hydrogen/deuterium exchange
      (HDX) techniques and how they provide complementary information that, when
      combined with crystallography, provide detailed insight into the function of
      nuclear receptors.

PMID- 22869590
TI  - Barry Thompson: the delicate choreography in growing epithelia. Interview by
      Caitlin Sedwick.

PMID- 22869591
TI  - The JCB DataViewer scales up.

PMID- 22869592
TI  - The ATM protein: the importance of being active.
AB  - The ataxia telangiectasia mutated (ATM) protein kinase regulates the cellular
      response to deoxyribonucleic acid (DNA) double-strand breaks by phosphorylating
      numerous players in the extensive DNA damage response network. Two papers in this
      issue (Daniel et al. 2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb201204035;
      Yamamoto et al. 2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb201204098)
      strikingly show that, in mice, the presence of a catalytically inactive version
      of ATM is embryonically lethal. This is surprising because mice completely
      lacking ATM have a much more moderate phenotype. The findings impact on basic
      cancer research and cancer therapeutics.

PMID- 22869593
TI  - A first line of defense against ER stress.
AB  - BiP is the predominant DnaK/Hsp70-type chaperone protein in the ER. It is
      required for folding and assembling newly synthesized ER client proteins, yet
      having too much BiP inhibits folding. In this issue, Chambers et al. (2012. J.
      Cell Biol. doi:10.1083/jcb.201202005) report that ADP ribosylation of BiP
      provides a reversible switch that fine tunes BiP activity according to need.

PMID- 22869594
TI  - The evolving concept of cancer and metastasis stem cells.
AB  - The cancer stem cell (CSC) concept, which arose more than a decade ago, proposed
      that tumor growth is sustained by a subpopulation of highly malignant cancerous
      cells. These cells, termed CSCs, comprise the top of the tumor cell hierarchy and
      have been isolated from many leukemias and solid tumors. Recent work has
      discovered that this hierarchy is embedded within a genetically heterogeneous
      tumor, in which various related but distinct subclones compete within the tumor
      mass. Thus, genetically distinct CSCs exist on top of each subclone, revealing a
      highly complex cellular composition of tumors. The CSC concept has therefore
      evolved to better model the complex and highly dynamic processes of
      tumorigenesis, tumor relapse, and metastasis.

PMID- 22869596
TI  - Kinase-dead ATM protein causes genomic instability and early embryonic lethality
      in mice.
AB  - Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic
      acid (DNA) damage responses by phosphorylating numerous substrates implicated in
      DNA repair and cell cycle checkpoint activation. A-T patients and mouse models
      that express no ATM protein undergo normal embryonic development but exhibit
      pleiotropic DNA repair defects. In this paper, we report that mice carrying
      homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic
      development. Atm(KD/-) cells exhibited proliferation defects and genomic
      instability, especially chromatid breaks, at levels higher than Atm(-/-) cells.
      Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed
      through variable, diversity, and joining recombination and immunoglobulin class
      switch recombination, two events requiring nonhomologous end joining, at levels
      comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential
      function of ATM during embryogenesis and an important function of catalytically
      inactive ATM protein in DNA repair.

PMID- 22869595
TI  - Loss of ATM kinase activity leads to embryonic lethality in mice.
AB  - Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA)
      damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and
      apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative
      disease, present with null mutations in Atm. To determine whether the functions
      of ATM are mediated solely by its kinase activity, we generated two mouse models
      containing single, catalytically inactivating point mutations in Atm. In this
      paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P
      mutations cause early embryonic lethality in mice, without displaying dominant
      negative interfering activity. Using conditional deletion, we find that the
      D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows
      greater deficiency in homologous recombination (HR) as measured by
      hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and
      increased genomic instability. These results may explain why missense mutations
      with no detectable kinase activity are rarely found in patients with classical A
      T. We propose that ATM kinase-inactive missense mutations, unless otherwise
      compensated for, interfere with HR during embryogenesis.

PMID- 22869597
TI  - All three components of the neuronal SNARE complex contribute to secretory
      vesicle docking.
AB  - Before exocytosis, vesicles must first become docked to the plasma membrane. The
      SNARE complex was originally hypothesized to mediate both the docking and fusion
      steps in the secretory pathway, but previous electron microscopy (EM) studies
      indicated that the vesicular SNARE protein synaptobrevin (syb) was dispensable
      for docking. In this paper, we studied the function of syb in the docking of
      large dense-core vesicles (LDCVs) in live PC12 cells using total internal
      reflection fluorescence microscopy. Cleavage of syb by a clostridial neurotoxin
      resulted in significant defects in vesicle docking in unfixed cells; these
      results were confirmed via EM using cells that were prepared using high-pressure
      freezing. The membrane-distal portion of its SNARE motif was critical for
      docking, whereas deletion of a membrane-proximal segment had little effect on
      docking but diminished fusion. Because docking was also inhibited by toxin
      mediated cleavage of the target membrane SNAREs syntaxin and SNAP-25, syb might
      attach LDCVs to the plasma membrane through N-terminal assembly of trans-SNARE
      pairs.

PMID- 22869598
TI  - ADP ribosylation adapts an ER chaperone response to short-term fluctuations in
      unfolded protein load.
AB  - Gene expression programs that regulate the abundance of the chaperone BiP adapt
      the endoplasmic reticulum (ER) to unfolded protein load. However, such programs
      are slow compared with physiological fluctuations in secreted protein synthesis.
      While searching for mechanisms that fill this temporal gap in coping with ER
      stress, we found elevated levels of adenosine diphosphate (ADP)-ribosylated BiP
      in the inactive pancreas of fasted mice and a rapid decline in this modification
      in the active fed state. ADP ribosylation mapped to Arg470 and Arg492 in the
      substrate-binding domain of hamster BiP. Mutations that mimic the negative charge
      of ADP-ribose destabilized substrate binding and interfered with interdomain
      allosteric coupling, marking ADP ribosylation as a rapid posttranslational
      mechanism for reversible inactivation of BiP. A kinetic model showed that
      buffering fluctuations in unfolded protein load with a recruitable pool of
      inactive chaperone is an efficient strategy to minimize both aggregation and
      costly degradation of unfolded proteins.

PMID- 22869599
TI  - Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and
      prion fragmentation.
AB  - Hsp100 and Hsp70 chaperones in bacteria, yeast, and plants cooperate to
      reactivate aggregated proteins. Disaggregation relies on Hsp70 function and on
      ATP-dependent threading of aggregated polypeptides through the pore of the Hsp100
      AAA(+) hexamer. In yeast, both chaperones also promote propagation of prions by
      fibril fragmentation, but their functional interplay is controversial. Here, we
      demonstrate that Hsp70 chaperones were essential for species-specific targeting
      of their Hsp100 partner chaperones ClpB and Hsp104, respectively, to heat-induced
      protein aggregates in vivo. Hsp70 inactivation in yeast also abrogated Hsp104
      targeting to almost all prions tested and reduced fibril mobility, which
      indicates that fibril fragmentation by Hsp104 requires Hsp70. The Sup35 prion was
      unique in allowing Hsp70-independent association of Hsp104 via its N-terminal
      domain, which, however, was nonproductive. Hsp104 overproduction even outcompeted
      Hsp70 for Sup35 prion binding, which explains why this condition prevented Sup35
      fragmentation and caused prion curing. Our findings indicate a conserved
      mechanism of Hsp70-Hsp100 cooperation at the surface of protein aggregates and
      prion fibrils.

PMID- 22869600
TI  - Seg1 controls eisosome assembly and shape.
AB  - Eisosomes are stable domains at the plasma membrane of the budding yeast
      Saccharomyces cerevisiae and have been proposed to function in endocytosis.
      Eisosomes are composed of two main cytoplasmic proteins, Pil1 and Lsp1, that form
      a scaffold around furrow-like plasma membrane invaginations. We show here that
      the poorly characterized eisosome protein Seg1/Ymr086w is important for eisosome
      biogenesis and architecture. Seg1 was required for efficient incorporation of
      Pil1 into eisosomes and the generation of normal plasma membrane furrows. Seg1
      preceded Pil1 during eisosome formation and established a platform for the
      assembly of other eisosome components. This platform was further shaped and
      stabilized upon the arrival of Pil1 and Lsp1. Moreover, Seg1 abundance controlled
      the shape of eisosomes by determining their length. Similarly, the
      Schizosaccharomyces pombe Seg1-like protein Sle1 was necessary to generate the
      filamentous eisosomes present in fission yeast. The function of Seg1 in the
      stepwise biogenesis of eisosomes reveals striking architectural similarities
      between eisosomes in yeast and caveolae in mammals.

PMID- 22869601
TI  - Virtual nanoscopy: generation of ultra-large high resolution electron microscopy
      maps.
AB  - A key obstacle in uncovering the orchestration between molecular and cellular
      events is the vastly different length scales on which they occur. We describe
      here a methodology for ultrastructurally mapping regions of cells and tissue as
      large as 1 mm(2) at nanometer resolution. Our approach employs standard
      transmission electron microscopy, rapid automated data collection, and stitching
      to create large virtual slides. It greatly facilitates correlative light-electron
      microscopy studies to relate structure and function and provides a genuine
      representation of ultrastructural events. The method is scalable as illustrated
      by slides up to 281 gigapixels in size. Here, we applied virtual nanoscopy in a
      correlative light-electron microscopy study to address the role of the
      endothelial glycocalyx in protein leakage over the glomerular filtration barrier,
      in an immunogold labeling study of internalization of oncolytic reovirus in human
      dendritic cells, in a cryo-electron microscopy study of intact vitrified mouse
      embryonic cells, and in an ultrastructural mapping of a complete zebrafish embryo
      slice.

PMID- 22869602
TI  - Andrographolide induces autophagic cell death in human liver cancer cells through
      cyclophilin D-mediated mitochondrial permeability transition pore.
AB  - Liver cancer is the third leading cause of cancer death worldwide and about half
      of the patients with liver cancer require adjuvant therapy after surgical
      resection. Therefore, development of novel agents to eradicate cancer cells may
      constitute a viable approach to treat patients with liver cancer.
      Andrographolide, a diterpenoid lactone isolated from Andrographis paniculata, is
      known to possess potent antioxidant, anti-inflammatory, antineoplastic and
      antiviral properties. In this study, we investigated the cytotoxic effect of
      andrographolide on human liver cancer cells and explored the cell death
      mechanism. Andrographolide induced a cell death distinct from apoptosis in
      multiple human liver cancer cells. The death was characterized by autophagy as
      evidenced by the accumulation of LC3 II and autophagosomes, and the formation of
      puncta GFP-LC3. This autophagy as well as cytotoxicity caused by andrographolide
      could be effectively prevented by 3-methyladenine (a chemical inhibitor of
      autophagy). Mechanistic study indicated that andrographolide induced autophagic
      cell death by disruption of mitochondrial transmembrane potential and elevation
      of reactive oxygen species, which were correlated with mitochondrial permeability
      transition pore Inhibition of cyclophilin D (a component of MPTP) by cyclosporin
      A or abrogation of its expression by small interfering RNA significantly
      suppressed the cytotoxicity of andrographolide, suggesting that cyclophilin D may
      play an important role in mediating andrographolide-induced cytotoxicity. Taken
      together, our findings unveil a novel mechanism of drug action by andrographolide
      in liver cancer cells and suggest that andrographolide may represent a promising
      novel agent in the treatment of liver cancer.

PMID- 22869603
TI  - OsDMI3 is a novel component of abscisic acid signaling in the induction of
      antioxidant defense in leaves of rice.
AB  - Ca(2+) and calmodulin (CaM) have been shown to play an important role in abscisic
      acid (ABA)-induced antioxidant defense. However, it is unknown whether Ca(2+)/CaM
      dependent protein kinase (CCaMK) is involved in the process. In the present
      study, the role of rice CCaMK, OsDMI3, in ABA-induced antioxidant defense was
      investigated in leaves of rice (Oryza sativa) plants. Treatments with ABA,
      H(2)O(2), and polyethylene glycol (PEG) induced the expression of OsDMI3 and the
      activity of OsDMI3, and H(2)O(2) is required for the ABA-induced increases in the
      expression and the activity of OsDMI3 under water stress. Subcellular
      localization analysis showed that OsDMI3 is located in the nucleus, the
      cytoplasm, and the plasma membrane. The analysis of the transient expression of
      OsDMI3 in rice protoplasts and the RNA interference (RNAi) silencing of OsDMI3 in
      rice protoplasts showed that OsDMI3 is required for ABA-induced increases in the
      expression and the activities of superoxide dismutase (SOD) and catalase (CAT).
      Further, the oxidative damage induced by higher concentrations of PEG and
      H(2)O(2) was aggravated in the mutant of OsDMI3. Moreover, the analysis of the
      RNAi silencing of OsDMI3 in protoplasts and the mutant of OsDMI3 showed that
      higher levels of H(2)O(2) accumulation require OsDMI3 activation in ABA
      signaling, but the initial H(2)O(2) production induced by ABA is not dependent on
      the activation of OsDMI3 in leaves of rice plants. Our data reveal that OsDMI3 is
      an important component in ABA-induced antioxidant defense in rice.

PMID- 22869604
TI  - Abstracts of the 32nd Annual Meeting of the National Academy of Neuropsychology.
      Nashville, Tennessee, USA. November 7-10, 2012.

PMID- 22869607
TI  - Down-regulation of S100A11, a calcium-binding protein, in human endometrium may
      cause reproductive failure.
AB  - BACKGROUND: Low expression levels of S100A11 proteins were demonstrated in the
      placental villous tissue of patients with early pregnancy loss, and S100A11 is a
      Ca2+-binding protein that interprets the calcium fluctuations and elicits various
      cellular responses. OBJECTIVES: The objective of the study was to determine
      S100A11 expression in human endometrium and its roles in endometrial receptivity
      and embryo implantation. METHODS: S100A11 expression in human endometrium was
      analyzed using quantitative RT-PCR, Western blot, and immunohistochemical
      techniques. The effects of S100A11 on embryo implantation were examined using in
      vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment
      assays. The effects of endometrial S100A11 on factors related to endometrial
      receptivity and immune responses were examined. Using a fluorescence method, we
      examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores
      in epidermal growth factor (EGF)-treated endometrial cells transfected with or
      without S100A11 small interfering RNA. RESULTS: S100A11 was expressed in human
      endometrium. S100A11 protein levels were significantly lower in endometrium of
      women with failed pregnancy than that in women with successful pregnancy
      outcomes. The knockdown of endometrial S100A11 not only reduced embryo
      implantation rate in mouse but also had adverse effects on the expression of
      factors related to endometrial receptivity and immune responses in human
      endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were
      mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial
      S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores,
      which was inhibited by the knockdown of S100A11. CONCLUSIONS: Endometrial S100A11
      is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium
      receptivity, and immunotolerance via affecting Ca2+ uptake and release from
      intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive
      failure.

PMID- 22869608
TI  - Impact of antenatal synthetic glucocorticoid exposure on endocrine stress
      reactivity in term-born children.
AB  - CONTEXT: Antenatal glucocorticoid (GC) exposure has been discussed as a potent
      programming factor of hypothalamus-pituitary-adrenal (HPA) axis activity,
      producing sustained alterations in cortisol secretion throughout life. So far,
      the assessment of HPA-axis activity in offspring of mothers treated with
      synthetic GC has been limited to a time period shortly after birth, with
      prematurity being an important confound in most prior studies. OBJECTIVE: The
      present study aimed to investigate HPA-axis reactivity of term-born children with
      antenatal GC exposure in a larger sample, allowing us to further address sex- and
      drug-specific effects. DESIGN, SETTING, AND PARTICIPANTS: This was a cross
      sectional study comprised of 209 term-born children between 6 and 11 yr of age.
      Cortisol secretion patterns in response to a standardized laboratory stressor
      (Trier Social Stress Test for Children) were assessed in children with antenatal
      GC exposure (a single course of either dexamethasone or betamethasone) and
      compared to different control groups. RESULTS: We observed significantly
      increased cortisol reactivity to acute psychosocial stress in 6- to 11-yr-old,
      term-born children exposed to antenatal synthetic GC treatment compared to
      controls (F(3.4,345.9)=5.8; P<0.001). This finding appeared to be independent of
      the specific synthetic GC used and was found to be more pronounced in females.
      CONCLUSIONS: The present study provides the first evidence for long-lasting
      effects of antenatal synthetic GC exposure on HPA-axis reactivity in term-born
      children. These findings may bear important implications regarding the
      vulnerability for stress-related physical and psychiatric disorders, for which
      dysregulation of the HPA-axis has been discussed as a potential causal factor.

PMID- 22869609
TI  - CRH activation of different signaling pathways results in differential calcium
      signaling in human pregnant myometrium before and during labor.
AB  - CONTEXT: Our previous study has demonstrated that CRH has differential effects on
      human uterine contractility before and after onset of labor. Intracellular Ca2+
      concentration ([Ca2+]i) mobilization plays an important role in the control of
      uterine contraction. OBJECTIVE: Our objective was to investigate the effects of
      CRH on [Ca2+]i homeostasis in laboring and nonlaboring myometrial cells and
      determine subsequent signaling involved in [Ca2+]i regulation by CRH. DESIGN: The
      myometrial tissues were obtained from pregnant women who were undergoing or not
      undergoing labor at term. [Ca2+]i was determined by Ca2+ imaging system using the
      fluorescent dye fura-2-acetoxymethyl ester. Western blot analysis, ELISA, and RIA
      were used to determine the signaling pathways induced by CRH. RESULTS: CRH
      induced Ca2+ transient in laboring cells, which was blocked by CRH receptor type
      1 (CRHR1) antagonist antalarmin. CRHR1 knockdown impaired this effect of CRH. CRH
      activated Gi protein, decreased cAMP production, and induced phosphorylated
      phospholipase C-beta3 and inositol-1,4,5-triphosphate production. Phospholipase C
      and inositol-1,4,5-triphosphate receptor inhibitors blocked the CRH-induced Ca2+
      transient in laboring cells. CRH did not induce whereas antalarmin induced the
      Ca2+ transient in nonlaboring cells. Knockdown of CRHR1 impaired the effect of
      antalarmin. CRH acted on CRHR1 to activate Gs in nonlaboring cells. Forskolin
      blocked antalarmin-induced Ca2+ transient. CONCLUSIONS: CRH acts on CRHR1 to
      activate different signaling pathways before and after onset of labor, thereby
      resulting in differential calcium signaling in response to CRH. The signaling
      pathways of CRHR1 might serve as a target for the development of new therapeutic
      strategies for preterm birth.

PMID- 22869610
TI  - Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of
      human lung epithelial cells and macrophages.
AB  - Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs)
      increase the production of reactive oxygen species (ROS) and oxidative stress
      related damage to DNA. However, the level of particle-generated genotoxicity may
      depend on interplay between different cell types, e.g. lung epithelium and immune
      cells. Macrophages have important immune defence functions by engulfing insoluble
      foreign materials, including particles, although they might also promote or
      enhance inflammation. We investigated the effect of co-culturing type II lung
      epithelial A549 cells with macrophages upon treatment with standard reference
      DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony
      forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated
      DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet
      assay as formamidopyrimidine-DNA glycosylase or oxoguanine DNA glycosylase
      (hOGG1) sensitive sites, in mono-cultures of A549 or THP-1a and co-cultures of
      A549 and THP-1a cells. The strongest genotoxic effects were observed in A549 mono
      cultures and SRM2975 was more potent than SRM1650b. The ROS production only
      increased in cells exposed to SRM2975, with strongest concentration-dependent
      effect in the THP-1a mono-cultures. The basal respiration level in THP-1a cells
      increased on exposure to SRM1650b and SRM2975 without indication of mitochondrial
      dysfunction. This is consistent with activation of the cells and there was no
      direct relationship between levels of respiration and ROS production. In
      conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to
      DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged
      DNA than A549 epithelial cells.

PMID- 22869611
TI  - Insensitivity of the in vitro cytokinesis-block micronucleus assay with human
      lymphocytes for the detection of DNA damage present at the start of the cell
      culture.
AB  - The cytokinesis-block micronucleus assay (CBMN assay) with cultured human
      lymphocytes is a well-established assay in genotoxicity testing and human
      biomonitoring. For both approaches, human lymphocytes are stimulated by
      phytohaemagglutinin (PHA) and cultured for about 72 h; 44 h after PHA
      stimulation, cytochalasin B (CytB) is added and micronuclei (MN) are scored in
      binucleated cells. The main difference between these two applications is the way
      lymphocytes are exposed to mutagens. In order to maximise the probability of
      detecting a mutagen, the OECD guideline 487 recommends starting the exposure to
      the test substance at 44-48 h after PHA stimulation. In human biomonitoring,
      blood samples are taken from subjects exposed to environmental mutagens in vivo
      and lymphocytes with induced DNA damage at the start of the cell culture are
      investigated with regard to potentially increased MN frequencies in binuclear
      lymphocytes. We compared the sensitivity of these two protocols by either
      treating lymphocyte cultures for 2h with known DNA-damaging mutagens at the start
      of the culture or 42 h after PHA stimulation. The mutagens used were methyl
      methanesulfonate (MMS), ethyl methanesulfonate (EMS), N-nitroso-N-ethylurea
      (ethyl nitrosourea; ENU), styrene oxide (SO), (+/-)-anti-B[a]P-7,8-dihydrodiol
      9,10-epoxide (BPDE) and mitomycin C (MMC). All substances induced MN under the
      conditions of the standard in vitro CBMN assay but only MMC clearly induced MN in
      lymphocytes exposed at the start of the culture. All mutagens (except MMC, a
      known crosslinker) were tested by the comet assay with blood cultures exposed at
      the start of the culture and clearly induced DNA migration. The nuclear division
      index (NDI) indicated that damaged lymphocytes proliferated well in these
      experiments. The lack of increased MN frequencies despite increased damage levels
      and good proliferation suggests that the CBMN assay is rather insensitive for the
      detection of mutagens/clastogens when damage is induced at the start of the blood
      cultures. Potential consequences for the interpretation of human biomonitoring
      studies are discussed in this article.

PMID- 22869612
TI  - The association between complement component 2/complement factor B polymorphisms
      and age-related macular degeneration: a HuGE review and meta-analysis.
AB  - The authors performed a systematic review of the association of complement
      component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related
      macular degeneration (AMD). In total, data from 19 studies published between 2006
      and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene
      and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for
      risk of bias were independently performed by 2 reviewers. Allele frequencies and
      allele and genotypic effects were pooled. Heterogeneity and publication bias were
      explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7% and
      9.6% for all polymorphisms, except for an Indian population in which the C allele
      at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele
      at rs9332739 and the minor T allele at rs547154 carried estimated relative risks
      (odds ratios) of 0.55 (95% confidence interval (CI): 0.46, 0.65) and 0.47 (95%
      CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at
      rs4151667 and rs614153 carried estimated risks of 0.54 (95% CI: 0.45, 0.64) and
      0.41 (95% CI: 0.34, 0.51), respectively. These allele effects contributed to an
      absolute lowering of the risk of all AMD in Caucasian populations by 2.0%-6.0%.
      This meta-analysis provides a robust estimate of the protective association of
      C2/CFB with AMD.

PMID- 22869613
TI  - Autophagy is a cell self-protective mechanism against arsenic-induced cell
      transformation.
AB  - Subchronic exposure to arsenic increases the incidence of human cancers such as
      skin, lung, colon, and rectal cancer. The mechanism for arsenic-induced
      tumorigenesis is still not clear. It is generally believed that DNA damage and
      genomic instability, generated by arsenic-promoted oxidative stress, account
      largely for this process. The major sources of reactive oxygen species (ROS) are
      arsenic-damaged mitochondria. Autophagy is a catabolic process functioning in
      turnover of long-lived proteins and dysfunctional organelles such as
      mitochondria. Defects of autophagy under stress conditions promote genomic
      instability and increase the risk of tumorigenesis. In the present study using a
      human bronchial epithelial cell line, BEAS-2B cells, we investigated the role of
      autophagy in arsenic-induced cell transformation, an important step in arsenic
      tumorigenesis. Our results show that subchronic arsenic exposure induces BEAS-2B
      cell transformation accompanied with increased ROS generation and autophagy
      activation. However, the patterns for ROS and autophagy alteration are different.
      Arsenic exposure generated a prolonged and steady increase of ROS levels, whereas
      the activation of autophagy, after an initial boost by arsenic administration,
      decreases in response to subchronic arsenic exposure, although the activity is
      still higher than a nontreated control. Further stimulation of autophagy
      increases mitochondria turnover and decreases ROS generation and arsenic-induced
      cell transformation. Contrarily, inhibition of autophagy activity decreases
      mitochondria turnover and enhances arsenic-induced ROS generation and cell
      transformation. In addition, the mammalian target of rapamycin signaling pathway
      is involved in arsenic-mediated autophagy activation. Our results suggest that
      autophagy is a cell self-protective mechanism against arsenic-induced cell
      transformation.

PMID- 22869614
TI  - Time is muscle ... even after reperfusion.

PMID- 22869616
TI  - alpha11 integrin stimulates myofibroblast differentiation in diabetic
      cardiomyopathy.
AB  - AIMS: Diabetic cardiomyopathy is characterized by the production of a
      disorganized fibrotic matrix in the absence of coronary atherosclerosis and
      hypertension. We examined whether adhesion of cardiac fibroblasts to glycated
      collagens mediates the differentiation of pro-fibrotic myofibroblasts, which may
      contribute to cardiac fibrosis. METHODS AND RESULTS: By microarray, we found that
      methylglyoxal-treated collagen selectively enhanced alpha11 integrin expression
      in human cardiac fibroblasts, while levels of other collagen-binding integrins
      (alpha1, alpha2, and alpha10) were unchanged. Similar increases in alpha11
      integrin mRNA and protein expression were observed in cardiac fibroblasts from
      streptozotocin (STZ)-treated Sprague-Dawley rats. In human cardiac fibroblasts
      plated on methyglyoxal-treated collagen and in cardiac fibroblasts from diabetic
      rats, transforming growth factor (TGF)-beta2 but not TGF-beta1 or TGF-beta3 was
      increased compared with controls. Knock-down of alpha11 integrin and TGF-beta
      receptors with small-interfering RNA blocked the increased expression of TGF
      beta2, alpha-smooth muscle actin (alpha-SMA), and alpha11 integrin that were
      induced in cells plated on methylglyoxal-treated collagen. Further, inhibition of
      Smad3 signalling blocked methylglyoxal-collagen up-regulation of alpha11 integrin
      and alpha-SMA expression. Rats with STZ-induced diabetes exhibited increased
      phosphorylation of Smad3 in cardiac tissues compared with control rats.
      CONCLUSION: Interactions between alpha11 integrins and the Smad-dependent TGF
      beta2 signalling may contribute to the formation of pro-fibrotic myofibroblasts
      and the development of a fibrotic interstitium in diabetic cardiomyopathy.

PMID- 22869617
TI  - Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats
      through the Tie2-nitric oxide pathway.
AB  - AIMS: Vascular reactivity shows biphasic changes after severe trauma or shock.
      Our aim was to elucidate the mechanisms of biphasic-changed vascular reactivity
      after haemorrhagic shock by observing the regulation of angiopoietin-1 (Ang-1)
      and angiopoietin-2 (Ang-2) on it. METHODS AND RESULTS: Haemorrhagic-shock Sprague
      Dawley rats, hypoxia-treated superior mesenteric arteries (SMAs) with intact
      endothelia, and a cell mixture of vascular smooth muscle cells (VSMCs) and
      vascular endothelial cells (VECs) were adopted to evaluate the regulatory effects
      of Ang-1 and Ang-2 on vascular reactivity and their relationship to Tie2
      (receptor tyrosine kinase)-Akt-endothelial nitric oxide synthase (eNOS) and Tie2
      extracellular signal-regulated kinase (Erk)-inducible nitric oxide synthase
      (iNOS) signal pathways. Ang-1 expression, Tie2 phosphorylation, and nitric oxide
      (NO) release were increased at early shock. Exogenous Ang-1 maintained the
      vascular reactivity of SMAs after early hypoxia. Tie2-blocking antibody and the
      antagonists of Akt and eNOS antagonized Ang-1-induced maintenance in vascular
      reactivity and a slight release in NO at the early stage of shock. Ang-2
      expression, Tie2 phosphorylation, and NO release were greatly increased at late
      shock, but exogenous Ang-2 further decreased the vascular reactivity of SMAs
      after late hypoxia. Tie2-blocking antibody and the antagonists of Erk and iNOS
      andtagonized the Ang-2-induced decrease in vascular reactivity and a large
      release of NO at the late stage of shock. CONCLUSION: Ang-1 and Ang-2
      participated in the regulation of vascular reactivity after haemorrhagic shock.
      Ang-1 was mainly responsible for the hyperreactivity at early shock through the
      Tie2-Akt-eNOS pathway and an appropriate amount of NO release. Ang-2 was mainly
      responsible for the hyporeactivity at late shock through the Tie2-Erk-iNOS
      pathway and the release of a large amount of NO.

PMID- 22869618
TI  - Angiotensin 1A receptors transfected into caudal ventrolateral medulla inhibit
      baroreflex gain and stress responses.
AB  - AIMS: The caudal ventrolateral medulla (CVLM) is important for autonomic
      regulation and is rich in angiotensin II type 1A receptors (AT(1A)R). To
      determine their function, we examined whether the expression of AT(1A)R in the
      CVLM of mice lacking AT(1A)R (AT(1A)(-/-)) alters baroreflex sensitivity and
      cardiovascular responses to stress. METHODS AND RESULTS: Bilateral
      microinjections into the CVLM of AT(1A)(-/-) mice of lentivirus with the phox-2
      selective promoter (PRSx8) were made to express either AT(1A)R (Lv-PRSx8-AT(1A))
      or green fluorescent protein (Lv-PRSx8-GFP) as a control. Radiotelemetry was used
      to record mean arterial pressure (MAP), heart rate (HR), and locomotor activity.
      Following injection of Lv-PRSx8-GFP, robust neuronal expression of GFP was
      observed with ~60% of the GFP-positive cells also expressing the catecholamine
      synthetic enzyme tyrosine hydroxylase. After 5 weeks, there were no differences
      in MAP or HR between groups, but the Lv-PRSx8-AT(1A)- injected mice showed
      reduced baroreflex sensitivity (-25%, P = 0.003) and attenuated pressor responses
      to cage-switch and restraint stress compared with the Lv-PRSx8-GFP-injected mice.
      Reduced MAP mid-frequency power during cage-switch stress reflected attenuated
      sympathetic activation (Pgroup * stress = 0.04). Fos-immunohistochemistry
      indicated greater activation of forebrain and hypothalamic neurons in the Lv
      PRSx8-AT(1A) mice compared with the control. CONCLUSION: The expression of
      AT(1A)R in CVLM neurons, including A1 neurons, while having little influence on
      the basal blood pressure or HR, may play a tonic role in inhibiting cardiac vagal
      baroreflex sensitivity. However, they strongly facilitate the forebrain response
      to aversive stress, yet reduce the pressor response presumably through greater
      sympatho-inhibition. These findings outline novel and specific roles for
      angiotensin II in the CVLM in autonomic regulation.

PMID- 22869619
TI  - Calcineurin regulates endothelial barrier function by interaction with and
      dephosphorylation of myosin phosphatase.
AB  - AIMS: Calcineurin (CN) influences myosin phosphorylation and alters endothelial
      barrier function; however, the molecular mechanism is still obscure. Here we
      examine whether CN controls myosin phosphorylation via mediating the
      phosphorylation state of Thr696 in myosin phosphatase (MP) target subunit 1
      (MYPT1), the phosphorylation site inhibitory to the catalytic activity of MP.
      METHODS AND RESULTS: Exposure of bovine or human pulmonary artery endothelial
      cells (BPAECs or HPAECs) to the CN inhibitor cyclosporin A (CsA) induces a rise
      in intracellular Ca(2+) and increases the phosphorylation level of cofilin(Ser3)
      and MYPT1(Thr696) in a Ca(2+)-and Rho-kinase-dependent manner. An active
      catalytic fragment of CN overexpressed in tsA201 cells decreases endogenous MYPT
      phospho-Thr696 (MYPT1(pThr696)) levels. Purified CN dephosphorylates (32)P
      labelled MYPT1, suggesting direct action of CN on this substrate. Interaction of
      MYPT1 with CN is revealed by MYPT1 pull-down experiments and colocalization in
      both BPAECs and HPAECs as well as by surface plasmon resonance (SPR)-based
      binding studies. Stabilization of the MYPT1-CN complex occurs via the
      MYPT1(300PLIEST305) sequence similar to the CN substrate-docking PxIxIT-motif.
      Thrombin induces a transient increase of MYPT1(pThr696) in BPAECs, whereas its
      combination with CsA results in maintained phosphorylation levels of both
      MYPT1(pThr696) and myosin. These phosphorylation events might correlate with
      changes in endothelial permeability since CsA slows down the recovery from the
      thrombin-induced decrease of the transendothelial electrical resistance of the
      BPAEC monolayer. CONCLUSION: CN may improve endothelial barrier function via
      inducing dephosphorylation of cofilin(pSer3) and by interaction with MYPT1 and
      activating MP through MYPT1(pThr696) dephosphorylation, thereby affecting actin
      polymerization and decreasing myosin phosphorylation.

PMID- 22869620
TI  - Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice.
AB  - AIMS: The molecular mechanisms controlling heart function and rhythmicity are
      incompletely understood. While it is widely accepted that the type 2 ryanodine
      receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction
      coupling, the role of these channels in setting a consistent beating rate remains
      controversial. Gain-of-function RYR2 mutations in humans and genetically
      engineered mouse models are known to cause Ca(2+) leak, arrhythmias, and sudden
      cardiac death. Embryonic stem-cell derived cardiomyocytes lacking Ryr2 display
      slower beating rates, but no supporting in vivo evidence has been presented. The
      aim of the present study was to test the hypothesis that RYR2 loss-of-function
      would reduce heart rate and rhythmicity in vivo. METHODS AND RESULTS: We
      generated inducible, tissue-specific Ryr2 knockout mice with acute ~50% loss of
      RYR2 protein in the heart but not in other tissues. Echocardiography, working
      heart perfusion, and in vivo ECG telemetry demonstrated that deletion of Ryr2 was
      sufficient to cause bradycardia and arrhythmia. Our results also show that
      cardiac Ryr2 knockout mice exhibit functional and structural hallmarks of heart
      failure, including sudden cardiac death. CONCLUSION: These results illustrate
      that the RYR2 channel plays an essential role in pacing heart rate. Moreover, we
      find that RYR2 loss-of-function can lead to fatal arrhythmias typically
      associated with gain-of-function mutations. Given that RYR2 levels can be reduced
      in pathological conditions, including heart failure and diabetic cardiomyopathy,
      we predict that RYR2 loss contributes to disease-associated bradycardia,
      arrhythmia, and sudden death.

PMID- 22869621
TI  - Primary CNS germ cell tumors in Japan and the United States: an analysis of 4
      tumor registries.
AB  - Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has
      been considered to be higher in East Asia than in the United States. This study
      estimates the incidence of CNS GCTs in Japan and the United States, investigates
      gender discrepancies in each country, and describes treatment outcomes. Data on
      primary CNS GCTs from 4 databases were utilized: population-based malignant
      incidence data from (1) the Japan Cancer Surveillance Research Group (2004-2006;
      14 registries), malignant and nonmalignant incidence data from (2) the
      Surveillance, Epidemiology, and End Results Program (2004-2008; 17 registries),
      and hospital-based observed survival data from (3) the Brain Tumor Registry of
      Japan (1984-2000) and (4) the US National Cancer Data Base (1990-2003). Incidence
      rates per 100 000 for malignant GCTs were not statistically significantly
      different between Japan (males = 0.143, females = 0.046) and the United States
      (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher
      for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan
      (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1,
      respectively). In general, 5-year survival estimates were high: over 75% for all
      GCTs, and over 81% for germinomas, regardless of the type of treatment in either
      Japan or the United States. The incidence of primary GCTs is similar between
      Japan and the United States and has the same gender-based patterns by location.
      High rates of survival were observed in both countries.

PMID- 22869622
TI  - A population-based study on the effect of temozolomide in the treatment of
      glioblastoma multiforme.
AB  - The effect of temozolomide (TMZ) and radiotherapy (RT) in the treatment of
      glioblastoma multiforme (GBM) has been well documented in randomized controlled
      trials. Here we present our findings on the effect of TMZ added to RT at a
      population level. The Cancer Registry of Norway was searched for patients with a
      GBM diagnosis from January 1, 2000 to December 31, 2007. Subsequently, the
      prescriptions registered to these patients were obtained from the Norwegian
      Prescription Database. The data were analyzed according to era (pre-TMZ
      introduction or post-TMZ introduction) and according to treatment received.
      Furthermore, a matching procedure was utilized to reduce the bias between the RT
      + TMZ and RT alone treatments so that the effect of TMZ could be better
      scrutinized. We identified 1157 GBM patients. The median overall survival (OS),
      in months, was 8.3 (95% confidence interval: 7.6-9.0) and 10.1 (95% confidence
      interval: 9.1-11.0) in the pre-TMZ and TMZ eras, respectively (P < .001). By
      treatment, we found median OS for the control, RT alone, and RT + TMZ groups to
      be 2.5, 9.0, and 16.2 months, respectively (P < .001). Two-year survival was 0%,
      4%, and 25%, respectively. The effect of age on TMZ effect was insignificant. In
      the matched group analysis, TMZ provided a 7.6-month OS benefit. Our population
      data reproduce the beneficial effect of TMZ from randomized controlled trials
      with a median OS of 16.2 months and 25% 2-year survival.

PMID- 22869623
TI  - Clinical and magnetic resonance imaging outcomes after surgical repair of
      complete proximal hamstring ruptures: does the tendon heal?
AB  - BACKGROUND: The use of validated outcome questionnaires and magnetic resonance
      imaging (MRI) when assessing outcomes after surgical treatment of proximal
      hamstring avulsions has been limited. PURPOSE: To comprehensively evaluate
      clinical, functional, and radiological outcomes in patients treated with surgical
      repair for complete proximal hamstring avulsions. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: A retrospective review of 15 consecutive patients
      was performed. Outcome measures included the Single Assessment Numeric Evaluation
      (SANE), visual analog scale (VAS) for pain, Proximal Hamstring Injury
      Questionnaire, Lower Extremity Functional Scale (LEFS), Harris Hip Score (HHS),
      and Tegner Activity Scale (TAS). Physical examination was performed by an
      independent sports medicine fellow. Magnetic resonance imaging of the lower
      extremity was used to assess tendon healing and muscle quality after repair.
      RESULTS: Thirteen of 15 (87%) eligible patients were available for follow-up at a
      mean 36.9 months (range, 27-63 months), including 8 men and 6 left-sided
      injuries. The average age was 44.6 years (range, 26-58 years). Twelve of 13
      patients underwent surgical repair within 60 days of injury. Mean (+/- standard
      deviation) postoperative functional outcome scores were as follows: LEFS, 74.9 +/
      7.8 (range, 59-80); HHS, 90.7 +/- 13.9 (range, 67-100); SANE, 93.6 +/- 7.5
      (range, 75-100); VAS for pain, 1.3 +/- 1.9 (range, 0-5); and TAS, 4.6 +/- 2.3
      (range, 1-7). All 11 patients who participated in sports before surgery were able
      to return to sport, but 45% reported a decrease in their current level of
      activity. Isokinetic muscle testing demonstrated that injured hamstring strength
      recovered up to 78% +/- 6.1% (range, 74%-88%) of the contralateral side. The MRI
      examinations revealed that 100% of patients had a healed proximal hamstring
      repair, with signs of tendinopathy and mild atrophy in 3 of 12 patients.
      CONCLUSION: The current findings indicate that surgical repair of complete
      hamstring ruptures provides reliable pain relief, good functional outcomes, high
      satisfaction rates, and excellent healing rates (MRI) but does not fully restore
      hamstring function and sports activity to preinjury levels.

PMID- 22869624
TI  - An anomalous accessory pectoralis major muscle: a case report.

PMID- 22869625
TI  - Acromioclavicular joint injuries in National Collegiate Athletic Association
      football: data from the 2004-2005 through 2008-2009 National Collegiate Athletic
      Association Injury Surveillance System.
AB  - BACKGROUND: Injuries to the shoulder are common in collegiate football, and
      injuries to the acromioclavicular (AC) joint have previously accounted for up to
      41% of all shoulder injuries. PURPOSE: To determine the incidence and
      epidemiology of injury to the AC joint in National Collegiate Athletic
      Association (NCAA) football athletes. STUDY DESIGN: Descriptive epidemiology
      study. METHODS: The NCAA Injury Surveillance System (ISS) men's football database
      was reviewed from the 2004-2009 playing seasons. The exposure data set from the
      same years was reviewed for the purposes of computing rates of injury per athlete
      exposure (AE). The injury rate (number of injuries divided by number of AEs) was
      computed per 10,000 AEs for competition and practice exposures. Ninety-five
      percent confidence intervals (95% CIs) for the incidence rates were calculated
      using assumptions of a Poisson distribution. RESULTS: According to the estimates
      made by the NCAA ISS, a total of 748 injuries to the AC joint occurred in NCAA
      football players during 2,222,155 AEs, accounting for 4.49% of all injuries
      sustained during this 5-year surveillance period. The overall rate of injury was
      3.34 per 10,000 AEs (95% CI, 3.10-3.59). Players were 11.68 (95% CI, 10.11-13.49)
      times more likely to sustain an injury in games than practices. Partial sprains
      (types I or II) accounted for 96.4% of injuries, while complete sprains (>=type
      III) accounted for the remaining 3.6%. The average amount of time lost per injury
      was 11.61 days. Complete sprains resulted in a mean time loss of 31.9 days (95%
      CI, 24.4-39.6) while partial injuries resulted in 11.0 days lost (95% CI, 9.6
      12.3). Overall, 2.41% of injuries underwent surgical intervention, with 22.2% of
      complete sprains and 1.7% of partial injuries resulting in surgery. Complete
      sprains of the AC joint were 13.5 (95% CI, 4.63-35.26) times more likely to
      result in surgical intervention than partial sprains. The majority of injuries
      (71.93%) resulted from contact with another player and 47.09% occurred while
      tackling or being tackled. Of all injuries, 47.63% occurred during offensive
      plays, while defense accounted for 20.77%. CONCLUSION: AC joint injuries in NCAA
      football players are predominantly low-grade sprains, leading to approximately 12
      days of lost competition. The few severe sprains that occurred often resulted in
      surgery or required approximately 5 weeks of rehabilitation.

PMID- 22869626
TI  - Survival of the anterior cruciate ligament graft and the contralateral ACL at a
      minimum of 15 years.
AB  - BACKGROUND: The risks for primary anterior cruciate ligament (ACL) rupture have
      been established. What is less well known is the risk of graft rupture after
      reconstruction and also the risk of a primary ACL rupture in the contralateral
      knee. PURPOSE: To determine the long-term survival of the ACL graft and the
      contralateral ACL (CACL) after reconstruction and to identify factors that
      increase the odds of subsequent ACL injury. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: All patients having undergone primary ACL reconstruction in
      1993 or 1994 by a single surgeon in a single unit were considered. Patients were
      contacted to complete a subjective interview by telephone or e-mail questionnaire
      at a minimum of 15 years after surgery. RESULTS: A total of 755 patients met the
      inclusion criteria, and ACL reconstruction was performed using a single-incision
      endoscopic technique with either autologous bone-patellar tendon-bone graft
      (BPTB; n = 314) or hamstring tendon graft (HT; n = 359) and metal interference
      screw fixation. Of these patients, 673 (89%) completed the questionnaire; 23% had
      sustained either a graft rupture or CACL rupture. Expected survival of the ACL
      graft was 95%, 93%, 91%, and 89% at a respective 2, 5, 10, and 15 years after
      reconstruction. Expected survival of the CACL was 97%, 93%, 90%, and 87%,
      respectively. Survival of the ACL graft was less favorable in men than in women
      (P = .007); ACL graft survival was not significantly different between the HT
      (88%) or BPTB (91%) groups (P = .149). Rupture of the CACL occurred twice as
      frequently as graft rupture in the BPTB group (graft survival, 84% vs 89%; P =
      .003). A positive family history of ACL rupture doubled the odds of both ACL
      graft and CACL rupture. The mean International Knee Documentation Committee
      subjective score at 15 years was 85. Return to preinjury sport levels was
      reported in 73% of patients, and 51% were still participating in strenuous or
      very strenuous activities at 15 years. CONCLUSION: Fifteen years after ACL
      reconstruction, expected survival of the ACL graft was 89% and expected survival
      of the CACL was 86%. Graft choice did not affect ACL graft rupture, but using
      BPTB increased the risk of CACL rupture compared with HT. Men had a less
      favorable survival rate of the ACL graft than did women, and a family history of
      ACL rupture increased the risk of both ACL graft and CACL rupture.

PMID- 22869627
TI  - Quantifying acromiohumeral distance in overhead athletes with glenohumeral
      internal rotation loss and the influence of a stretching program.
AB  - BACKGROUND: Loss of internal rotation range of motion (ROM) on the dominant side
      is well documented in athletes performing overhead sports activity. This altered
      motion pattern has been shown to change glenohumeral and scapular kinematics.
      This could compromise the subacromial space and explain the association between
      glenohumeral internal rotation deficit (GIRD) and subacromial impingement.
      PURPOSE: First, to quantify acromiohumeral distance (AHD) and compare between the
      dominant and nondominant side in overhead athletes with GIRD of more than 15
      degrees . Second, to investigate the effect of a sleeper stretch program on ROM
      and AHD. STUDY DESIGN: Controlled laboratory study. METHODS: Range of motion was
      measured with a digital inclinometer and AHD was measured with ultrasound in 62
      overhead athletes with GIRD (>15 degrees ) at baseline. Differences between sides
      were analyzed. Athletes were randomly allocated to the stretch (n = 30) or
      control group (n = 32). The stretch group performed a 6-week sleeper stretch
      program on the dominant side. Change of range of motion and AHD were measured and
      analyzed in both groups after 6 weeks. RESULTS: The dominant side showed a
      significant internal rotation deficit (-24.7 degrees  +/- 6.3 degrees ) and
      horizontal adduction deficit (-11.8 degrees  +/- 7.4 degrees ) and the dominant
      side AHD was significantly smaller with the arm at neutral (-0.4 +/- 0.6 mm) and
      at 45 degrees  (-0.5 +/- 0.8 mm) and 60 degrees  (-0.6 +/- 0.7 mm) of active
      abduction compared with the nondominant side. After stretching, significant
      increase of internal rotation (+13.5 degrees  +/- 0.8 degrees ), horizontal
      adduction (+10.6 degrees  +/- 0.9 degrees ) ROM and AHD (+0.5 to +0.6mm) was
      observed at the dominant side of the stretch group compared with prestretching
      measurements. No significant change of AHD was seen in the nondominant side of
      the stretch group and in both sides of the control group. CONCLUSION: The AHD, a
      2-dimensional measure for subacromial space, was found to be smaller on the
      dominant side in athletes with GIRD and was found to increase after a 6-week
      sleeper stretch program. CLINICAL RELEVANCE: These findings might provide insight
      into the relation between GIRD and subacromial impingement but future studies are
      needed to determine clinical implications.

PMID- 22869628
TI  - Arthroscopic capsular plication for microtraumatic anterior shoulder instability
      in overhead athletes.
AB  - BACKGROUND: Extreme loading conditions at the glenohumeral joint during overhead
      athletic activities can result in both soft tissue and osseous adaptative changes
      at the shoulder. Subtle alterations in the stabilizing structures may lead to
      anterior instability and debilitating shoulder pain with subsequent inability to
      participate in athletics. There is currently a paucity of data documenting
      clinical outcomes after arthroscopic capsular plication in overhead athletes who
      demonstrate objective findings of pain and anterior instability on physical
      examination. PURPOSE: To evaluate outcomes after arthroscopic capsular plication
      for anterior instability in overhead athletes with an emphasis on postoperative
      range of motion, postoperative shoulder function, and return to sport. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: The authors identified 20
      overhead athletes with debilitating shoulder pain and a failed trial of
      nonoperative management who underwent arthroscopic capsular plication (12 suture
      plication, 8 suture anchor plication) for anterior instability related to
      isolated capsular redundancy. Patients were evaluated with the Single Assessment
      Numerical Evaluation (SANE) and Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder
      and Elbow Score, and they were interviewed to determine the rate of return to
      athletic activity. Failures of treatment included patients who demonstrated
      debilitating pain that precluded return to sport. RESULTS: At a mean follow-up of
      3.6 years (range, 2.0-5.5 years), 18 (90%) patients returned to overhead sports,
      with 17 (85%) at their preinjury level. The mean (SD) SANE score was 86 (17.5%;
      range, 30%-100%), and the mean (SD) KJOC score was 82 (18.2; range, 28-100). When
      compared with the contralateral extremity, there were no significant differences
      in glenohumeral range of motion. Two patients with associated rotator cuff injury
      experienced persistent pain with overhead activity and were unable to return to
      sport, representing a 10% failure rate. CONCLUSION: Arthroscopic capsular
      plication for anterior instability related to isolated capsular redundancy is an
      effective procedure that yields a high rate of patient satisfaction and return to
      overhead athletic activity with an acceptably low failure rate. Patients with
      associated rotator cuff injury may be at higher risk for treatment failure.

PMID- 22869629
TI  - In vivo endoscopic imaging of ancylostomiasis-induced gastrointestinal bleeding:
      clinical and biological profiles.
AB  - Little data are available regarding the association of ancylostomiasis with overt
      gastrointestinal bleeding. This 6-year retrospective study describes the clinical
      and biological profiles of unexpectedly identified ancylostomiasis in a 4-month
      old baby and four adults; they presented with melena and were referred for urgent
      diagnostic gastrointestinal endoscopy, which confirmed numerous small intestine
      injuries with surrounding blood pools caused by Ancylostoma duodenale worms.
      Gastric erosions were also encountered in one patient. Uniquely, worm biological
      activities were recorded live in vivo, including mucosal invasion through a
      vigorous, rapid piercing process, repeated bloodsucking habits, and gut
      appearance during the stages of feeding, digestion, and excretion in male and
      female worms. In conclusion, ancylostomiasis-induced melena may occur in all ages
      from infants to the elderly. Worm bloodfeeding occurs after quick mucosal
      piercing, with blood loss being aggravated by a repeated feeding behavior. After
      treatment is started, bleeding stops rapidly in response to anthelmintic therapy.

PMID- 22869630
TI  - Autogeny in Culex pipiens complex mosquitoes from the San Francisco Bay Area.
AB  - We surveyed the genetic ancestry and recorded the occurrence of autogeny, the
      developmental times, and survival rates in families of Culex pipiens in Santa
      Clara County, CA, at 37 degrees N latitude. Females in 95% of the families
      produced fertile egg rafts without access to blood (= autogeny) after mating in
      stenogamous conditions. Developmental time, survival, and egg raft production
      were closely correlated to temperature. Male DV/D ratios overwhelmingly matched
      Cx. pipiens but a microsatellite analysis revealed these were Cx. pipiens form
      molestus hybridized with Culex quinquefasciatus and to a lesser extent to Cx.
      pipiens form pipiens, a genetic mix heretofore not recorded elsewhere. Greater
      DV/D ratios and larger proportions of genetic ancestry from Cx. quinquefasciatus
      were negatively correlated to autogeny. The combination of multiple overwintering
      strategies and widespread autogeny in females arising from aboveground larval
      sites supports the hypothesis that some North American populations of Cx. pipiens
      complex mosquitoes express unusual phenologies.

PMID- 22869631
TI  - Impact of a hygiene curriculum and the installation of simple handwashing and
      drinking water stations in rural Kenyan primary schools on student health and
      hygiene practices.
AB  - School-based hygiene and water treatment programs increase student knowledge,
      improve hygiene, and decrease absenteeism, however health impact studies of these
      programs are lacking. We collected baseline information from students in 42
      schools in Kenya. We then instituted a curriculum on safe water and hand hygiene
      and installed water stations in half ("intervention schools"). One year later, we
      implemented the intervention in remaining schools. Through biweekly student
      household visits and two annual surveys, we compared the effect of the
      intervention on hygiene practices and reported student illness. We saw
      improvement in proper handwashing techniques after the school program was
      introduced. We observed a decrease in the median percentage of students with
      acute respiratory illness among those exposed to the program; no decrease in
      acute diarrhea was seen. Students in this school program exhibited sustained
      improvement in hygiene knowledge and a decreased risk of respiratory infections
      after the intervention.

PMID- 22869632
TI  - Low entomological impact of new water supply infrastructure in southern Vietnam,
      with reference to dengue vectors.
AB  - We did a prospective study in southern Vietnam where new water infrastructure was
      added. New 1,200-L tanks may present potential breeding grounds for Aedes
      aegypti, particularly when sealed lids were not always supplied. Some
      householders in these communes received a piped water supply, however there was
      no reduction in water storage practices. The prevalence of Aedes aegypti
      immatures in tank and tap households reached 73%, but were non-significantly
      different from each other and from control households that received no
      infrastructure. In all three communes, standard jars comprised from 48% to 71% of
      containers but were associated with > 90% of III-IV instars and pupae on
      occasions. In contrast, project tanks contributed from 0-21% of the total
      population. Non-functional or no lids were apparent 4 months after installation
      in 45-76% of new tanks, but there was no difference between communes with lids
      and without lids.

PMID- 22869633
TI  - ELISA with recombinant rKRP42 antigen using urine samples: a tool for predicting
      clinical visceral leishmaniasis cases and its outbreak.
AB  - We reported a highly sensitive and specific enzyme-linked immunosorbent assay
      (ELISA) that detects immunoglobulin G (IgG) in urine using rKRP42 antigen for the
      diagnosis of visceral leishmaniasis (VL). The ELISA was applied to study
      chronological change in antibody titers in five study areas in Rajshahi district,
      Bangladesh. A total of 585 subjects without a past VL history were examined at
      least three times in the 30-month follow-up period; of these subjects, 137
      (23.4%) subjects became ELISA-positive at least one time during the study. Among
      the positive cases, 40 (29.2%) subjects developed clinical VL, and 31 (77.5%) of
      these subjects showed IgG titers of >= 1,000 U more than one time in the study
      period. Considering only the first ELISA results, 22 subjects with IgG titers of
      >= 1,000 U could be found, and 21 (95.5%) of these subjects turned out to be
      clinical cases. The high urinary IgG titers (>= 1,000 U) will help predict
      possible clinical VL cases and thus, identify an outbreak in its earlier stage.

PMID- 22869634
TI  - Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine
      in an immunocompetent soldier.
AB  - A 38-year-old male immunocompetent soldier developed generalized seizures. He
      underwent surgical debulking and a progressive demyelinating pseudotumor was
      identified. Serology and molecular testing confirmed a diagnosis of granulomatous
      amoebic encephalitis caused by Acanthamoeba sp. in this immunocompetent male. The
      patient was treated with oral voriconazole and miltefosine with Acanthamoeba
      titers returning to control levels and serial imaging demonstrating resolution of
      the residual lesion.

PMID- 22869635
TI  - Magnetic affinity enzyme-linked immunoassay for diagnosis of Schistosomiasis
      japonicum in persons with low-intensity infection.
AB  - Most schistosome-endemic areas in China are characterized by low-intensity
      infections that are independent of prevalence. To establish an effective
      diagnostic method, we developed a magnetic affinity enzyme-linked immunoassay
      based on soluble egg antigens (SEA-MEIA) for diagnosing schistosomiasis in
      persons with low-intensity infection with Schistosoma japonicum by comparing it
      with a conventional enzyme-linked immunosorbent assay (ELISA). Our results showed
      that the SEA-MEIA had a higher sensitivity and greater precision in the diagnosis
      of low-intensity S. japonicum infections than the ELISA. In addition, when we
      used Pearson's correlation in associating SEA-MEIA with ELISA, a significant
      correlation existed between the two assays (r = 0.845, P < 0.001). Our data
      indicated that SEA-MEIA, with a higher sensitivity and greater ease of
      performance, would be valuable for diagnosis of schistosomiasis japonicum in
      persons with low-intensity infections.

PMID- 22869636
TI  - Epidemic distribution and variation of Plasmodium falciparum and Plasmodium vivax
      malaria in Hainan, China during 1995-2008.
AB  - Hainan Province is the main area threatened by malaria in China. However, the
      epidemiologic patterns of malaria in this region are not yet defined. In this
      study, we determined the spatio-temporal distribution and variation of Plasmodium
      falciparum and Plasmodium vivax malaria in Hainan during 1995-2008 by using
      wavelet and cluster quantitative approaches. The results indicated a decreasing
      secular trend and obvious seasonal fluctuation of malaria in Hainan. In addition,
      the characteristic annual peak of malaria could not be detected after 2005. The
      south-central region of Hainan has remained an area of relatively high malaria
      risk, but the incidence of P. falciparum malaria increased significantly in the
      southeast and southwest regions during 2002-2008. These findings identify
      epidemic patterns of malaria in Hainan, and are applicable for designing an
      effective and dynamic public health campaign to combat malaria in this region.

PMID- 22869637
TI  - Quantifying external load in Australian football matches and training using
      accelerometers.
AB  - PURPOSE: To describe the external load of Australian football matches and
      training using accelerometers. METHODS: Nineteen elite and 21 subelite Australian
      footballers wore accelerometers during matches and training. Accelerometer data
      were expressed in 2 ways: from all 3 axes (player load; PL) and from all axes
      when velocity was below 2 m/s (PLSLOW). Differences were determined between 4
      playing positions (midfielders, nomadics, deeps, and ruckmen), 2 playing levels
      (elite and subelite), and matches and training using percentage change and effect
      size with 90% confidence intervals. RESULTS: In the elite group, midfielders
      recorded higher PL than nomadics and deeps did (8.8%, 0.59 +/- 0.24; 34.2%, 1.83
      +/- 0.39 respectively), and ruckmen were higher than deeps (37.2%, 1.27 +/-
      0.51). Elite midfielders, nomadics, and ruckmen recorded higher PLSLOW than deeps
      (13.5%, 0.65 +/- 0.37; 11.7%, 0.55 +/- 0.36; and 19.5%, 0.83 +/- 0.50,
      respectively). Subelite midfielders were higher than nomadics, deeps, and ruckmen
      (14.0%, 1.08 +/- 0.30; 31.7%, 2.61 +/- 0.42; and 19.9%, 0.81 +/- 0.55,
      respectively), and nomadics and ruckmen were higher than deeps for PL (20.6%,
      1.45 +/- 0.38; and 17.4%, 0.57 +/- 0.55, respectively). Elite midfielders,
      nomadics, and ruckmen recorded higher PL (7.8%, 0.59 +/- 0.29; 12.9%, 0.89 +/-
      0.25; and 18.0%, 0.67 +/- 0.59, respectively) and PLSLOW (9.4%, 0.52 +/- 0.30;
      11.3%, 0.68 +/- 0.25; and 14.1%, 0.84 +/- 0.61, respectively) than subelite
      players. Small-sided games recorded the highest PL and PLSLOW and were the only
      training drill to equal or exceed the load from matches across positions and
      playing levels. CONCLUSION: PL differed between positions, with midfielders the
      highest, and between playing levels, with elite higher. Differences between
      matches and training were also evident, with PL from small-sided games equivalent
      to or higher than matches.

PMID- 22869638
TI  - Evaluation of change-of-direction movements in young rugby players.
AB  - The evaluation of change-of-direction (COD) performance is strongly focused on
      the time spent to perform the test trials, while much less is known about the
      technical execution adopted during the COD movements. Thus, the purposes of this
      study were to evaluate (1) the relationship between straight- and COD-sprint
      tests and (2) the technical execution of COD movements in relation to different
      age categories of young rugby players. Young rugby players (N = 157, age range 8
      19 y) completed a test battery composed of a 15-m straight-sprint test (15SS) and
      a 15-m sprint test performed with 2 changes of direction (15COD). Significant
      differences were detected between age categories for both tests. Significant
      correlations were found between 15SS and 15COD. The analysis of the technical
      execution of the 15COD test showed differences between age categories, with a
      prevalence of rounded turns up to the U15 category. These findings confirmed the
      relationship between straight and COD abilities in young male rugby players.
      Moreover, the new approach introduced by this study, based on the analysis of COD
      technical execution, revealed that this performance could be conditioned by the
      age and mastery level of the players.

PMID- 22869639
TI  - Comparison of agility demands of small-sided games in elite Australian football.
AB  - PURPOSE: To compare the agility demands of 4 small-sided games (SSGs) and
      evaluate the variability in demands for elite Australian Football (AF). METHODS:
      Fourteen male elite Australian Football League (AFL) players (mean +/- SD; 21.7
      +/- 3.1 y, 189.6 +/- 9.0 cm, 88.7 +/- 10.0 kg, 39.4 +/- 57.1 games) completed 4
      SSGs of 3 * 45-s bouts each with modified designs. Video notational analysis, GPS
      at 5 Hz, and triaxial accelerometer data expressed the external player loads
      within games. Three comparisons were made using a paired t test (P < .05), and
      magnitudes of differences were reported with effect size (ES) statistics.
      RESULTS: Reduced area per player (increased density) produced a small increase in
      total agility maneuvers (SSG1, 7.2 +/- 1.3; SSG2, 8.8 +/- 4.1), while a large 2D
      player load was accumulated (P < .05, ES = 1.22). A reduction in players produced
      a moderate (ES = 0.60) total number of agility maneuvers (SSG 3, 11.3 +/- 6.1;
      SSG 2, 8.3 +/- 3.6); however, a greater variability was found. The implementation
      of a 2-handed-tag rule resulted in a somewhat trivial decline (P > .05, ES =
      0.16) in agility events compared with normal AFL tackling rules (SSG 2, 8.3 +/-
      3.6; SSG 4, 7.8 +/- 2.6). CONCLUSIONS: SSG characteristics can influence agility
      training demand, which can vary considerably for individuals. Coaches should
      carefully consider SSG design to maximize the potential to develop agility for
      all players.

PMID- 22869640
TI  - Amateur boxing: activity profile of winners and losers.
AB  - An activity profile of competitive 3 * 2-min novice-level amateur boxing was
      created based on video footage and postbout blood [La] in 32 male boxers (mean +/
      SD) age 19.3 +/- 1.4 y, body mass 62.6 +/- 4.1 kg. Winners landed 18 +/- 11 more
      punches than losers by applying more lead-hand punches in round 1 (34.2 +/- 10.9
      vs 26.5 +/- 9.4), total punches to the head (121.3 +/- 10.2 vs 96.0 +/- 9.8), and
      block and counterpunch combinations (2.8 +/- 1.1 vs. 0.1 +/- 0.2) over all 3
      rounds and punching combinations (44.3 +/- 6.4 vs 28.8 +/- 6.7) in rounds 1 and 3
      (all P < .05). In 16 boxers, peak postbout blood [La] was 11.8 +/- 1.6 mmol/L
      irrespective of winning or losing. The results suggest that landing punches
      requires the ability to maintain a high frequency of attacking movements, in
      particular the lead-hand straight punch to the head together with punching
      combinations. Defensive movements must initiate a counterattack. Postbout blood
      [La] suggests that boxers must be able to tolerate a lactate production rate of
      1.8 mmol . L-1 . min-1 and maintain skillful techniques at a sufficient activity
      rate.

PMID- 22869641
TI  - The safety net, Medicaid, and a 'two-state solution'?

PMID- 22869642
TI  - The Affordable Care Act largely survives the Supreme Court's scrutiny--but
      barely.
AB  - In a 5-4 vote, the Court upholds the constitutionality of the individual mandate
      but effectively gives states the option of expanding Medicaid.

PMID- 22869643
TI  - The Supreme Court's surprising decision on the Medicaid expansion: how will the
      federal government and states proceed?
AB  - In National Federation of Independent Business v. Sebelius, the US Supreme Court
      upheld the constitutionality of the requirement that all Americans have
      affordable health insurance coverage. But in an unprecedented move, seven
      justices first declared the mandatory Medicaid eligibility expansion
      unconstitutional. Then five justices, led by Chief Justice John Roberts,
      prevented the outright elimination of the expansion by fashioning a remedy that
      simply limited the federal government's enforcement powers over its provisions
      and allowed states not to proceed with expanding Medicaid without losing all of
      their federal Medicaid funding. The Court's approach raises two fundamental
      issues: First, does the Court's holding also affect the existing Medicaid program
      or numerous other Affordable Care Act Medicaid amendments establishing minimum
      Medicaid program requirements? And second, does the health and human services
      secretary have the flexibility to modify the pace or scope of the expansion as a
      negotiating strategy with the states? The answers to these questions are key
      because of the foundational role played by Medicaid in health reform.

PMID- 22869644
TI  - In 2011 nearly one-third of physicians said they would not accept new Medicaid
      patients, but rising fees may help.
AB  - When fully implemented, the Affordable Care Act will expand the number of people
      with health insurance. This raises questions about the capacity of the health
      care workforce to meet increased demand. I used data on office-based physicians
      from the 2011 National Ambulatory Medical Care Survey Electronic Medical Records
      Supplement to summarize the percentage of physicians currently accepting any new
      patients. Although 96 percent of physicians accepted new patients in 2011, rates
      varied by payment source: 31 percent of physicians were unwilling to accept any
      new Medicaid patients; 17 percent would not accept new Medicare patients; and 18
      percent of physicians would not accept new privately insured patients. Physicians
      in smaller practices and those in metropolitan areas were less likely than others
      to accept new Medicaid patients. Higher state Medicaid-to-Medicare fee ratios
      were correlated with greater acceptance of new Medicaid patients. The findings
      serve as a useful baseline from which to measure the anticipated impact of
      Affordable Care Act provisions that could boost Medicaid payment rates to primary
      care physicians in some states while increasing the number of people with health
      care coverage.

PMID- 22869645
TI  - Strained local and state government finances among current realities that
      threaten public hospitals' profitability.
AB  - This study demonstrates that some safety-net hospitals--those that provide a
      large share of the care to low-income, uninsured, and Medicaid populations-
      survived and even thrived before the recent recession. We analyzed the financial
      performance and governance of 150 hospitals during 2003-07. We found,
      counterintuitively, that those directly governed by elected officials and in
      highly competitive markets were more profitable than other safety-net hospitals.
      They were financially healthy primarily because they obtained subsidies from
      state and local governments, such as property tax transfers or supplemental
      Medicaid payments, including disproportionate share payments. However, safety-net
      hospitals now face a new market reality. The economic downturn, slow recovery,
      and politics of deficit reduction have eroded the ability of local governments to
      support the safety net. Many safety-net hospitals have not focused on effective
      management, cost control, quality improvement, or services that attract insured
      patients. As a result, and coupled with new uncertainties regarding Medicaid
      expansion stemming from the recent Supreme Court decision on the Affordable Care
      Act, many are likely to face increasing financial and competitive pressures that
      may threaten their survival.

PMID- 22869646
TI  - How five leading safety-net hospitals are preparing for the challenges and
      opportunities of health care reform.
AB  - Safety-net hospitals will continue to play a critical role in the US health care
      system, as they will need to care for the more than twenty-three million people
      who are estimated to remain uninsured after the Affordable Care Act is
      implemented. Yet such hospitals will probably have less federal and state support
      for uncompensated care. At the same time, safety-net hospitals will need to
      reposition themselves in the marketplace to compete effectively for newly insured
      people who will have a choice of providers. We examine how five leading safety
      net hospitals have begun preparing for reform. Building upon strong
      organizational attributes such as health information technology and system
      integration, the study hospitals' preparations include improving the efficiency
      and quality of care delivery, retaining current and attracting new patients, and
      expanding the medical home model.

PMID- 22869647
TI  - Safety-net providers in some US communities have increasingly embraced
      coordinated care models.
AB  - Safety-net organizations, which provide health services to uninsured and low
      income people, increasingly are looking for ways to coordinate services among
      providers to improve access to and quality of care and to reduce costs. In this
      analysis, a part of the Community Tracking Study, we examined trends in safety
      net coordination activities from 2000 to 2010 within twelve communities in the
      United States and found a notable increase in such activities. Six of the twelve
      communities had made formal efforts to link uninsured people to medical homes and
      coordinate care with specialists in 2010, compared to only two communities in
      2000. We also identified key attributes of safety-net coordinated care systems,
      such as reliance on a medical home for meeting patients' primary care needs, and
      lingering challenges to safety-net integration, such as competition among
      hospitals and community health centers for Medicaid patients.

PMID- 22869648
TI  - Integrating community health centers into organized delivery systems can improve
      access to subspecialty care.
AB  - The Affordable Care Act is funding the expansion of community health centers to
      increase access to primary care, but this approach will not ensure effective
      access to subspecialty services. To address this issue, we interviewed directors
      of twenty community health centers. Our analysis of their responses led us to
      identify six unique models of how community health centers access subspecialty
      care, which we called Tin Cup, Hospital Partnership, Buy Your Own Subspecialists,
      Telehealth, Teaching Community, and Integrated System. We determined that the
      Integrated System model appears to provide the most comprehensive and cohesive
      access to subspecialty care. Because Medicaid accountable care organizations
      encourage integrated delivery of care, they offer a promising policy solution to
      improve the integration of community health centers into "medical neighborhoods."

PMID- 22869649
TI  - In ten California counties, notable progress in system integration within the
      safety net, although challenges remain.
AB  - When fully implemented, the Affordable Care Act will expand insurance coverage to
      the currently uninsured, and experiments in delivery and payment under the law's
      auspices could produce greater efficiencies in how care is delivered. Both
      factors may accelerate the development of one viable model to streamline care,
      integrated delivery systems--coordinated care networks that deliver all needed
      health services to a defined population. Through interviews and surveys, we
      examined ten California counties that participated in two federally and locally
      funded initiatives to redesign how care is delivered to predominantly poor and
      uninsured populations. We found substantial progress in assessing and managing
      access to specialists, monitoring and promoting quality, and offering disease
      management and care coordination training in a majority of counties. However,
      efforts to coordinate care, electronically disseminate patient information, and
      align financial incentives were less successful or more difficult to assess. We
      posit that integrated delivery systems could improve care efficiency and quality
      and make countywide safety-net systems a desirable source of care for newly
      insured patients under health reform.

PMID- 22869650
TI  - Shining a light on the reinvention of the safety net.

PMID- 22869651
TI  - The post-Katrina conversion of clinics in New Orleans to medical homes shows
      change is possible, but hard to sustain.
AB  - Hurricane Katrina destroyed much of the health care infrastructure in and around
      New Orleans in 2005. We describe a natural experiment that occurred afterward,
      amid efforts to rebuild the city's health care system, in which diverse safety
      net clinics were transformed into medical homes. Using surveys of clinic leaders
      and administrative data, we found that clinics made substantial progress in
      implementing new clinical processes to improve access, quality and safety, and
      care coordination and integration. But there was wide variation, with some
      clinics making only minimal progress. Because the transformation was closely tied
      to the receipt of federal grants and bonus payments, we observed declines in
      performance toward the end of the study, when clinics faced diminished federal
      funding and refocused their priorities on survival. Now that federal funds have
      dried up, moreover, clinics may be losing ground in sustaining their practice
      changes. The experience shows that payment to support medical home transformation
      must be robust and stable, and clinics need to be fully integrated into the
      broader health care system to improve overall coordination of care.

PMID- 22869652
TI  - Based on key measures, care quality for Medicare enrollees at safety-net and non
      safety-net hospitals was almost equal.
AB  - Safety-net hospitals, which include urban hospitals serving large numbers of low
      income, uninsured, and otherwise vulnerable populations, have historically faced
      greater financial strains than hospitals that serve more affluent populations.
      These strains can affect hospitals' quality of care, perhaps resulting in worse
      outcomes that are commonly used as indicators of care quality-mortality and
      readmission rates. We compared risk-standardized rates of both of these clinical
      outcomes among fee-for-service Medicare beneficiaries admitted for acute
      myocardial infarction, heart failure, or pneumonia. These beneficiaries were
      admitted to urban hospitals within Metropolitan Statistical Areas that contained
      at least one safety-net and at least one non-safety-net hospital. We found that
      outcomes varied across the urban areas for both safety-net and non-safety-net
      hospitals for all three conditions. However, mortality and readmission rates were
      broadly similar, with non-safety-net hospitals outperforming safety-net hospitals
      on average by less than one percentage point across most conditions. For heart
      failure mortality, there was no difference between safety-net and non-safety-net
      hospitals. These findings suggest that safety-net hospitals are performing better
      than many would have expected.

PMID- 22869653
TI  - Case studies at Denver Health: 'patient dumping' in the emergency department
      despite EMTALA, the law that banned it.
AB  - The Emergency Medical Treatment and Labor Act was enacted in 1986 to prevent
      hospitals from turning away patients with emergency medical conditions, often
      because they were uninsured--a practice commonly known as "patient dumping."
      Twenty-five years later, Denver Health--a large, urban, safety-net hospital-
      continues to experience instances in which people with emergency conditions, many
      of whom are uninsured, end up in the safety-net setting after having been denied
      care or receiving incomplete care elsewhere. We present five case studies and
      discuss potential limitations in the oversight and enforcement of the 1986 law.
      We advocate for a more effective system for reporting and acting on potential
      violations, as well as clearer standards governing compliance with the law.

PMID- 22869654
TI  - Solutions to emergency department 'boarding' and crowding are underused and may
      need to be legislated.
AB  - The practice of keeping admitted patients on stretchers in hospital emergency
      department hallways for hours or days, called "boarding," causes emergency
      department crowding and can be harmful to patients. Boarding increases patients'
      morbidity, lengths of hospital stay, and mortality. Strategies that optimize bed
      management reduce boarding by improving the efficiency of hospital patient flow,
      but these strategies are grossly underused. Convincing hospital leaders of the
      value of such solutions, and educating patients to advocate for such changes, may
      promote improvements. If these strategies do not work, legislation may be
      required to effect meaningful change.

PMID- 22869656
TI  - The promise and peril of accountable care for vulnerable populations: a framework
      for overcoming obstacles.
AB  - Accountable care organizations (ACOs) are a promising payment model aimed at
      reducing costs while also improving the quality of care. However, there is a risk
      that vulnerable populations may not be fully incorporated into this new model. We
      define two distinct vulnerable populations, clinically at-risk and socially
      disadvantaged, and we discuss how ACOs may benefit each group. We provide a
      framework to use in considering challenges for both vulnerable patients and
      health systems on the path to accountable care. We identify policies that can
      help overcome these obstacles: strategies that support ACO formation in diverse
      settings and that monitor, measure, and reward the performance of providers that
      reach all patients, including vulnerable populations.

PMID- 22869655
TI  - California hospitals serving large minority populations were more likely than
      others to employ ambulance diversion.
AB  - It is well documented that racial and ethnic minority populations
      disproportionately use hospital emergency departments for safety-net care. But
      what is not known is whether emergency department crowding is disproportionately
      affecting minority populations and potentially aggravating existing health care
      disparities, including poorer outcomes for minorities. We examined ambulance
      diversion, a proxy measure for crowding, at 202 California hospitals. We found
      that hospitals serving large minority populations were more likely to divert
      ambulances than were hospitals with a lower proportion of minorities, even when
      controlling for hospital ownership, emergency department capacity, and other
      hospital demographic and structural factors. These findings suggest that
      establishing more-uniform criteria to regulate diversion may help reduce
      disparities in access to emergency care.

PMID- 22869657
TI  - A discharge panel at Denver Health, focused on complex patients, may have
      influenced decline in length-of-stay.
AB  - Acute care hospitals struggle to manage complex patients who no longer require
      acute care services but who present medical and psychosocial challenges that make
      safe discharge to a lower level of care difficult. These challenges can be
      particularly acute at safety-net hospitals that cater predominantly to the poor
      and uninsured. For a person with a serious illness, such as a spinal cord injury,
      lack of insurance for long-term care services may add many weeks of medically
      unnecessary hospital days and result in higher costs. We describe safety-net
      system Denver Health's efforts to facilitate appropriate nonhospital care for
      these complex patients through the formation of a Complex Discharge Subcommittee.
      Successful solutions include accelerating legal guardianship approval to
      facilitate patient acceptance by skilled nursing facilities, as well as providing
      specialized equipment such as bariatric beds to nursing facilities to enable them
      to accommodate these patients. However, further policy interventions, such as
      updated reimbursement policies, are warranted.

PMID- 22869658
TI  - Increase in federal match associated with significant gains in coverage for
      children through Medicaid and CHIP.
AB  - As the number of children living in poverty has increased steadily over the past
      decade, Medicaid and the Children's Health Insurance Program (CHIP) have enrolled
      millions of additional youths. Federal and state governments jointly finance both
      programs, with the federal portion determined by the Federal Medical Assistance
      Percentage, commonly known as the "federal match." The federal government has
      used intermittent increases in the federal match as a way to provide fiscal
      relief to states during economic downturns. The most recent broad increase ended
      in June 2011, but the precise impact on Medicaid and CHIP enrollment for children
      is not known. No previous study has evaluated the association of the federal
      match with children's enrollment in state Medicaid or CHIP programs in the
      context of other state factors. To shed light on the degree to which public
      coverage for children varies with differences in the federal match, we examined
      publicly available data from all fifty states from 1999 to 2009. We found that a
      ten-percentage-point increase in the federal match was associated with a 1.9
      percent increase in Medicaid and CHIP enrollment, equivalent to approximately
      500,000 children. This association persisted when adjusted for multiple state
      level factors, including the proportion of children living in poverty. This
      analysis underscores the central role of the federal match in supporting
      expansion of Medicaid and CHIP coverage for children.

PMID- 22869659
TI  - Differences in life expectancy due to race and educational differences are
      widening, and many may not catch up.
AB  - It has long been known that despite well-documented improvements in longevity for
      most Americans, alarming disparities persist among racial groups and between the
      well-educated and those with less education. In this article we update estimates
      of the impact of race and education on past and present life expectancy, examine
      trends in disparities from 1990 through 2008, and place observed disparities in
      the context of a rapidly aging society that is emerging at a time of optimism
      about the next revolution in longevity. We found that in 2008 US adult men and
      women with fewer than twelve years of education had life expectancies not much
      better than those of all adults in the 1950s and 1960s. When race and education
      are combined, the disparity is even more striking. In 2008 white US men and women
      with 16 years or more of schooling had life expectancies far greater than black
      Americans with fewer than 12 years of education-14.2 years more for white men
      than black men, and 10.3 years more for white women than black women. These gaps
      have widened over time and have led to at least two "Americas," if not multiple
      others, in terms of life expectancy, demarcated by level of education and racial
      group membership. The message for policy makers is clear: implement educational
      enhancements at young, middle, and older ages for people of all races, to reduce
      the large gap in health and longevity that persists today.

PMID- 22869660
TI  - A hospital system's response to a hurricane offers lessons, including the need
      for mandatory interfacility drills.
AB  - This case study explores the lessons learned when the North Shore-Long Island
      Jewish Health System, a large, integrated health network in New York, evacuated
      three hospitals at high risk of flooding from Hurricane Irene in August 2011. The
      episode resulted in the evacuation, transport, and placement of 947 patients
      without any resulting deaths or serious injuries. This case demonstrates the
      utility of having in place a functional evacuation plan, such as the one North
      Shore-Long Island Jewish Health System developed through its own full-scale
      exercises in the years following Hurricane Katrina in 2005. In those drills, the
      health system discovered that it needed to abandon its 1:1 matching of patients
      to available beds in the region in favor of the group transport of patients with
      similar needs to facilities that could accommodate them. Despite its overall
      success, the system identified the need for internal improvements, including
      automated patient tracking through the use of bar-coded wristbands and
      identification and training of additional backup personnel for its emergency
      operations center. Among other changes, policy makers at the state and federal
      levels should consider mandating full-scale interfacility evacuation drills to
      refine mechanisms to send and receive patients.

PMID- 22869661
TI  - Substantial Medicare savings may result if insurers cover 'artificial pancreas'
      sooner for diabetes patients.
AB  - Technologies to improve diabetes care have advanced considerably with the
      introduction of the insulin pump and continuous glucose monitoring. These two
      technologies are now being joined and enhanced to create an artificial pancreas.
      The current study models the impact of the artificial pancreas on clinical
      results and costs over time, based on early results from clinical trials. The
      modeling shows that insurers' coverage of the cost of an artificial pancreas at a
      relatively early point in the life of a patient with diabetes would greatly
      reduce future complications of the disease and spending needed to treat such
      complications. Projected Medicare savings are $937 million in nominal dollars
      after twenty-five years. The results of this analysis support conducting a more
      comprehensive trial to assess the long-term impact of the artificial pancreas on
      glucose levels and the technology's related costs.

PMID- 22869662
TI  - Medical groups can reduce costs by investing in improved quality of care for
      patients with diabetes.
AB  - A major feature of many new contracts between providers and payers is shared
      savings programs, in which providers can earn a percentage of the savings if the
      cost of the care they provide is lower than the projected cost. Unless providers
      are also held accountable for meeting quality benchmarks, some observers fear
      that these programs could erode quality of care by rewarding only cost savings.
      We estimated the effects on Medicare expenditures of improving the quality of
      care for patients with diabetes. Analyzing 234 practices that provided care for
      133,703 diabetic patients, we found a net savings of $51 per patient with
      diabetes per year for every one-percentage-point increase in a score of the
      quality of care. Cholesterol testing for all versus none of a practice's patients
      with diabetes, for example, was associated with a dramatic drop in avoidable
      hospitalizations. These results show that improving the quality of care for
      patients with diabetes does save money.

PMID- 22869663
TI  - Greater adherence to diabetes drugs is linked to less hospital use and could save
      nearly $5 billion annually.
AB  - Improving adherence to medication offers the possibility of both reducing costs
      and improving care for patients with chronic illness. We examined a national
      sample of diabetes patients from 2005 to 2008 and found that improved adherence
      to diabetes medications was associated with 13 percent lower odds of subsequent
      hospitalizations or emergency department visits. Similarly, losing adherence was
      associated with 15 percent higher odds of these outcomes. Based on these and
      other effects, we project that improved adherence to diabetes medication could
      avert 699,000 emergency department visits and 341,000 hospitalizations annually,
      for a saving of $4.7 billion. Eliminating the loss of adherence (which occurred
      in one out of every four patients in our sample) would lead to another $3.6
      billion in savings, for a combined potential savings of $8.3 billion. These
      benefits were particularly pronounced among poor and minority patients. Our
      analysis suggests that improved adherence among patients with diabetes should be
      a key goal for the health care system and policy makers. Strategies might include
      reducing copayments for certain medications or providing feedback about adherence
      to patients and providers through electronic health records.

PMID- 22869664
TI  - Low cognitive ability and poor skill with numbers may prevent many from enrolling
      in Medicare supplemental coverage.
AB  - Because traditional Medicare leaves substantial gaps in coverage, many people
      obtain supplemental coverage to limit their exposure to out-of-pocket costs.
      However, some Medicare beneficiaries may not be well equipped to navigate the
      complex supplemental coverage landscape successfully because of their lower
      cognitive ability or numeracy--that is, the ability to work with numbers. We
      found that people in the lower third of the cognitive ability and numeracy
      distributions were at least eleven percentage points less likely than those in
      the upper third to enroll in a supplemental Medicare insurance plan. This result
      means that many Medicare beneficiaries do not have the financial protections and
      other benefits that would be available to them if they were enrolled in a
      supplemental insurance plan. Our findings suggest that policy makers may want to
      consider alternatives tailored to these high-need groups, such as enhanced
      education and enrollment programs, simpler sets of plan choices, or even some
      type of automatic enrollment with an option to decline coverage.

PMID- 22869665
TI  - Two arms, two choices: if only I'd known then what I know now.

PMID- 22869668
TI  - Willingness to pay for cancer therapy.

PMID- 22869670
TI  - Decision making by patients and physicians together.

PMID- 22869672
TI  - Medical coverage of former inmates.

PMID- 22869674
TI  - Adverse drug event reporting.

PMID- 22869675
TI  - Why current reimbursement rates are inefficient.

PMID- 22869676
TI  - Significance of intraplaque neovascularisation for vulnerability: optical
      coherence tomography study.
AB  - OBJECTIVES: This study aimed to investigate the role of intraplaque
      neovascularisation (NV) in culprit lesions and non-culprit lesions of unstable
      angina pectoris (UAP) and in lesions of stable angina pectoris (SAP) using
      optical coherence tomography (OCT). DESIGN: This study was a retrospective study.
      SETTING: The significance of NV for culprit and non-culprit plaques remains
      unclear. PARTICIPANTS: A total of 356 plaques from 92 UAP patients and 25 SAP
      patients who underwent OCT imaging were divided into three groups: culprit
      lesions in UAP (92), non-culprit lesions in UAP (203) and lesions of SAP (61).
      MAIN OUTCOME MEASURES: NV and plaque characteristics were examined by OCT and
      plaques with and without NV were compared. RESULTS: Among UAP culprit lesions,
      plaques with NV had significantly higher incidence of thin cap fibroatheroma (81%
      vs 47%, p=0.002) compared with those without NV. In addition, the fibrous cap was
      thinner (56+/-20 MUm vs 75+/-30 MUm, p<0.001), lipid arc was greater (254+/-66
      degrees  vs 222+/-65 degrees , p=0.024) and lipid core length was longer (13+/-5
      mm vs 10+/-6 mm, p=0.007). No significant difference was observed between non
      culprit lesions of UAP with and without NV, and between lesions of SAP with and
      without NV. CONCLUSION: In patients with UAP, the culprit plaques with NV had
      vulnerable features such as thinner fibrous cap, greater lipid arc, longer lipid
      core length and more frequent thin cap fibroatheroma compared with those without
      NV. In both non-culprit lesions of UAP patients and in lesions of SAP patients NV
      was not associated with vulnerable plaque characteristics.

PMID- 22869677
TI  - Exercise capacity and stroke volume are preserved late after tetralogy repair,
      despite severe right ventricular dilatation.
AB  - OBJECTIVES: To assess if exercise capacity and resting stroke volume are
      different in tetralogy of Fallot (TOF) repair survivors with indexed RV (right
      ventricle) end-diastolic volume (RVEDVi) more versus less than 150 ml/m(2), a
      currently suggested threshold for pulmonary valve replacement (PVR). DESIGN:
      Cross-sectional study. SETTING: Single-centre adult congenital heart disease
      unit. PATIENTS: 55 consecutively eligible patients with repaired TOF (age at
      repair 2.3+/-1.9 years; age at evaluation 26.2+/-8.8 years; NYHA Class I or II).
      INTERVENTIONS: Cardiovascular MRI (1.5T) and cardiopulmonary exercise test. MAIN
      OUTCOME MEASURES: Biventricular volumes and function; exercise capacity. RESULTS:
      20 patients had RVEDVi below, and 35 had RVEDVi above 150 ml/m(2), at time of
      referral. In the >150 ml/m(2) group, fractional pulmonary regurgitation was
      higher (41+/-8 vs 31+/-8%, p<0.001). Although RV ejection fraction (EF) was lower
      (47+/-7 vs 54+/-6%, p=0.007), indexed RV stroke volume was higher (87+/-14 vs
      64+/-10 ml/m(2), p<0.001) in the >150 ml/m(2) group. There were no significant
      differences in LVEF, indexed LV stroke volume or exercise capacity (% predicted
      peak work: 90+/-17 vs 89+/-11% and; % predicted VO(2) peak: 84+/-17 vs 87+/-12%).
      CONCLUSIONS: Exercise capacity and stroke volume are maintained with RVEDVi above
      compared with below a commonly used cut-off for PVR surgery. Optimal timing for
      PVR, thus, remains unclear.

PMID- 22869678
TI  - Intravenous immunoglobulin plus corticosteroid to prevent coronary artery
      abnormalities in Kawasaki disease: a meta-analysis.
AB  - OBJECTIVE: To summarise clinical trials that compared the incidence of coronary
      abnormality between intravenous immune globulin (IVIG) plus corticosteroid
      therapy and IVIG therapy alone, and to determine the overall efficacy and safety
      of IVIG plus corticosteroid therapy for the initial treatment of Kawasaki
      disease. BACKGROUND: Although use of IVIG as initial therapy has been established
      in Kawasaki disease, the role of corticosteroids therapy is controversial.
      METHODS: Medline, The Cochrane Library, The Clinical Trials, and Embase Database
      were searched for published clinical studies up to 31 March 2012. Studies that
      compare the efficacy of IVIG plus corticosteroid with that of IVIG in treating
      Kawasaki disease were included. The coronary outcome and adverse events were
      analysed by meta-analysis. RESULTS: 9 clinical studies with a total of 1011
      patients were identified. Meta-analysis of the 9 studies showed that IVIG plus
      corticosteroid therapy significantly reduced the risk of coronary abnormality
      (OR: 0.3; 95% CI 0.20 to 0.46). Similar results were observed in subgroup
      analyses of randomised controlled studies (OR: 0.3; 95% CI 0.18 to 0.5), studies
      focused on patients with a high risk of IVIG resistance (OR: 0.2; 95% CI 0.1 to
      0.36) and studies with blinded-endpoint manner (OR: 0.32; 95% CI 0.19 to 0.55).
      There was no significant difference in the incidence of severe adverse events
      between the IVIG plus corticosteroid group, and the IVIG group (OR: 1.24; 95% CI
      0.33 to 4.67). CONCLUSIONS: Combination of corticosteroid with the conventional
      regimen of IVIG as an initial treatment strategy could reduce the risk of
      coronary abnormality.

PMID- 22869679
TI  - Opa3, a novel regulator of mitochondrial function, controls thermogenesis and
      abdominal fat mass in a mouse model for Costeff syndrome.
AB  - The interrelationship between brown adipose tissue (BAT) and white adipose tissue
      (WAT) is emerging as an important factor in obesity, but the effect of impairing
      non-shivering thermogenesis in BAT on lipid storage in WAT remains unclear. To
      address this, we have characterized the metabolic phenotype of a mouse model for
      Costeff syndrome, in which a point mutation in the mitochondrial membrane protein
      Opa3 impairs mitochondrial activity. Opa3(L122P) mice displayed an 80% reduction
      in insulin-like growth factor 1, postnatal growth retardation and hepatic
      steatosis. A 90% reduction in uncoupling protein 1 (UCP1) expression in
      interscapular BAT was accompanied by a marked reduction in surface body
      temperature, with a 2.5-fold elevation in interscapular BAT mass and lipid
      storage. The sequestration of circulating lipid into BAT resulted in profound
      reductions in epididymal and retroperitoneal WAT mass, without affecting
      subcutaneous WAT. The histological appearance and intense mitochondrial staining
      in intra-abdominal WAT suggest significant 'browning', but with UCP1 expression
      in WAT of Opa3(L122P) mice only 62% of that in wild-type littermates, any
      precursor differentiation does not appear to result in thermogenically active
      beige adipocytes. Thus, we have identified Opa3 as a novel regulator of lipid
      metabolism, coupling lipid uptake with lipid processing in liver and with
      thermogenesis in BAT. These findings indicate that skeletal and metabolic
      impairment in Costeff syndrome may be more significant than previously thought
      and that uncoupling lipid uptake from lipid metabolism in BAT may represent a
      novel approach to controlling WAT mass in obesity.

PMID- 22869680
TI  - Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal
      by a beta-cyclodextrin.
AB  - Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused
      primarily by loss-of-function mutations in NPC1 gene, is characterized
      neuropathologically by intracellular cholesterol accumulation, gliosis and
      neuronal loss in selected brain regions. Recent studies have shown that NPC
      disease exhibits intriguing parallels with Alzheimer's disease (AD), including
      the presence of tau-positive neurofibrillary tangles (NFTs) and beta-amyloid
      (Abeta)-related peptides in vulnerable brain regions. Since enhanced cholesterol
      level, which acts as a risk factor for AD, can increase Abeta production by
      regulating amyloid precursor protein (APP) metabolism, it is possible that APP
      overexpression can influence cholesterol-regulated NPC pathology. We have
      addressed this issue in a novel bigenic mice (ANPC) generated by crossing
      heterozygous Npc1-deficient mice with mutant human APP transgenic mice. These
      mice exhibited decreased lifespan, early object memory and motor impairments, and
      exacerbated glial pathology compared with other littermates. Neurodegeneration
      observed in the cerebellum of ANPC mice was found to be accelerated along with a
      selective increase in the phosphorylation/cleavage of tau protein. Additionally,
      enhanced levels/activity of cytosolic cathepsin D together with cytochrome c and
      Bcl-2-associated X protein suggest a role for the lysosomal enzyme in the caspase
      induced degeneration of neurons in ANPC mice. The reversal of cholesterol
      accretion by 2-hydroxypropyl-beta-cyclodextrin (2-HPC) treatment increased
      longevity and attenuated behavioral/pathological abnormalities in ANPC mice.
      Collectively, our results reveal that overexpression of APP in Npc1-deficient
      mice can negatively influence longevity and a wide spectrum of
      behavioral/neuropathological abnormalities, thus raising the possibility that APP
      and NPC1 may interact functionally to regulate the development of AD and NPC
      pathologies.

PMID- 22869685
TI  - Isothiocyanates from Wasabia japonica activate transient receptor potential
      ankyrin 1 channel.
AB  - 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) and 6-(methylthio)hexyl
      isothiocyanate (6-MTITC) have low pungency and are responsible for the fresh
      flavor of wasabi (Wasabia japonica [Miq] Matsumura). In this study, we found that
      these two isothiocyanates activate transient receptor potential ankyrin 1
      (TRPA1), and 6-MSITC activates transient receptor potential vanilloid 1 (TRPV1),
      but not other transient receptor potential channels expressed in sensory neurons.
      Both 6-MSITC and 6-MTITCinduced intracellular Ca(2+) increases in human embryonic
      kidney-derived 293 cells expressing mouse TRPA1 (mTRPA1) as measured by Ca(2+)
      imaging. In whole-cell patch-clamp recordings, 6-MSITC and 6-MTITC dose
      dependently activated both mTRPA1 (EC(50) = 147+/-26 uM for 6-MSITC and 30+/-3 uM
      for 6-MTITC) and human TRPA1 (hTRPA1; EC(50) = 39+/-4 uM for 6-MSITC and 34+/-3
      uM for 6-MTITC). In addition, TRPA1 N-terminal cysteines, which are reported to
      be important for channel activation by electrophilic ligands, were involved in 6
      MSITC- and 6-MTITC-evoked TRPA1 activation. These isothiocyanates also activated
      endogenous TRPA1 expressed in mouse dorsal root ganglion neurons and intraplantar
      injection of 10-30 mM 6-MSITC-evoked pain-related behaviors in mice. These
      results indicate the following: 1) 6-MSITC and 6-MTITC activate both mTRPA1 and
      hTRPA1; 2) 6-MSITC activates mTRPV1; and 3) the pharmacological functions of
      these isothiocyanates could be derived from TRPA1 activation.

PMID- 22869686
TI  - Evidence for genetic factors in vasovagal syncope: a twin-family study.
AB  - OBJECTIVE: Vasovagal syncope (VVS) is the most frequent type of syncope and a
      common differential diagnosis of epilepsy. The role of genetic factors in VVS is
      debated. We performed a twin-family study to clarify this question and to analyze
      the putative mode of inheritance. METHODS: Fifty-one same-sex twin pairs where at
      least 1 had syncope were ascertained. The twins were interviewed via telephone
      using a standardized questionnaire. Available medical records were obtained.
      Information on the affected status of first- and second-degree relatives was
      acquired. RESULTS: There was a trend toward higher casewise concordance in
      monozygous (MZ, 0.75) than dizygous (DZ, 0.50) twins for any syncope (p = 0.06).
      Significant and strong effects on concordance between MZ and DZ twins were found
      for fainting at least twice unrelated to external circumstances (0.71 vs 0.27, p
      = 0.018) and for syncope associated with typical vasovagal triggers (0.62 vs
      0.00, p < 0.001). Twelve of 19 concordant MZ twin pairs reported sparse or no
      other affected family members whereas in the other 7 pairs multiple close
      relatives were affected. CONCLUSIONS: The twin analysis provides strong evidence
      for the relevance of genetic factors in VVS. Analysis of the families suggests
      that complex inheritance (multiple genes +/- environmental factors) is usual,
      with rarer families possibly segregating a major autosomal dominant gene.

PMID- 22869687
TI  - Isolated intramedullary spinal artery aneurysm.

PMID- 22869688
TI  - Clinical reasoning: a case of treatable spastic paraparesis.

PMID- 22869689
TI  - Pearls & oy-sters: maternally inherited diabetes and deafness presenting with
      ptosis and macular pattern dystrophy.

PMID- 22869691
TI  - Teaching neuroimages: carotid body tumor as a novel cause of cerebral ischemic
      stroke.

PMID- 22869692
TI  - India-Asia collision timing.

PMID- 22869693
TI  - Human arrival scenarios have a strong influence on interpretations of the late
      Quaternary extinctions.

PMID- 22869694
TI  - Lack of correspondence between Asian-Papuan genetic admixture and Austronesian
      language dispersal in eastern Indonesia.

PMID- 22869695
TI  - Three-dimensional microfluidic model for tumor cell intravasation and endothelial
      barrier function.
AB  - Entry of tumor cells into the blood stream is a critical step in cancer
      metastasis. Although significant progress has been made in visualizing tumor cell
      motility in vivo, the underlying mechanism of cancer cell intravasation remains
      largely unknown. We developed a microfluidic-based assay to recreate the tumor
      vascular interface in three-dimensions, allowing for high resolution, real-time
      imaging, and precise quantification of endothelial barrier function. Studies are
      aimed at testing the hypothesis that carcinoma cell intravasation is regulated by
      biochemical factors from the interacting cells and cellular interactions with
      macrophages. We developed a method to measure spatially resolved endothelial
      permeability and show that signaling with macrophages via secretion of tumor
      necrosis factor alpha results in endothelial barrier impairment. Under these
      conditions intravasation rates were increased as validated with live imaging. To
      further investigate tumor-endothelial (TC-EC) signaling, we used highly invasive
      fibrosarcoma cells and quantified tumor cell migration dynamics and TC-EC
      interactions under control and perturbed (with tumor necrosis factor alpha)
      barrier conditions. We found that endothelial barrier impairment was associated
      with a higher number and faster dynamics of TC-EC interactions, in agreement with
      our carcinoma intravasation results. Taken together our results provide evidence
      that the endothelium poses a barrier to tumor cell intravasation that can be
      regulated by factors present in the tumor microenvironment.

PMID- 22869697
TI  - Identification of an N-terminal inhibitory extension as the primary
      mechanosensory regulator of twitchin kinase.
AB  - Titin-like kinases are an important class of cytoskeletal kinases that intervene
      in the response of muscle to mechanical stimulation, being central to myofibril
      homeostasis and development. These kinases exist in autoinhibited states and,
      allegedly, become activated during muscle activity by the elastic unfolding of a
      C-terminal regulatory segment (CRD). However, this mechano-activation model
      remains controversial. Here we explore the structural, catalytic, and tensile
      properties of the multidomain kinase region of Caenorhabditis elegans twitchin
      (Fn(31)-Nlinker-kinase-CRD-Ig(26)) using X-ray crystallography, small angle X-ray
      scattering, molecular dynamics simulations, and catalytic assays. This work
      uncovers the existence of an inhibitory segment that flanks the kinase N
      terminally (N-linker) and that acts synergistically with the canonical CRD tail
      to silence catalysis. The N-linker region has high mechanical lability and acts
      as the primary stretch-sensor in twitchin kinase, while the CRD is poorly
      responsive to pulling forces. This poor response suggests that the CRD is not a
      generic mechanosensor in this kinase family. Instead, the CRD is shown here to be
      permissive to catalysis and might protect the kinase active site against
      mechanical damage. Thus, we put forward a regulatory model where kinase
      inhibition results from the combined action of both N- and C-terminal tails, but
      only the N-terminal extension undergoes mechanical removal, thereby affording
      partial activation. Further, we compare invertebrate and vertebrate titin-like
      kinases and identify variations in the regulatory segments that suggest a
      mechanical speciation of these kinase classes.

PMID- 22869698
TI  - Rational, combinatorial, and genomic approaches for engineering L-tyrosine
      production in Escherichia coli.
AB  - Although microbial metabolic engineering has traditionally relied on rational and
      knowledge-driven techniques, significant improvements in strain performance can
      be further obtained through the use of combinatorial approaches exploiting
      phenotypic diversification and screening. Here, we demonstrate the combined use
      of global transcriptional machinery engineering and a high-throughput L-tyrosine
      screen towards improving L-tyrosine production in Escherichia coli. This
      methodology succeeded in generating three strains from two separate mutagenesis
      libraries (rpoA and rpoD) exhibiting up to a 114% increase in L-tyrosine titer
      over a rationally engineered parental strain with an already high capacity for
      production. Subsequent strain characterization through transcriptional analysis
      and whole genome sequencing allowed complete phenotype reconstruction from well
      defined mutations and point to important roles for both the acid stress
      resistance pathway and the stringent response of E. coli in imparting this
      phenotype. As such, this study presents one of the first examples in which cell
      wide measurements have helped to elucidate the genetic and biochemical
      underpinnings of an engineered cellular property, leading to the total
      restoration of metabolite overproduction from specific chromosomal mutations.

PMID- 22869699
TI  - Quantitation of ten 30S ribosomal assembly intermediates using fluorescence
      triple correlation spectroscopy.
AB  - The self-assembly of bacterial 30S ribosomes involves a large number of RNA
      folding and RNA-protein binding steps. The sequence of steps determines the
      overall assembly mechanism and the structure of the mechanism has ramifications
      for the robustness of biogenesis and resilience against kinetic traps.
      Thermodynamic interdependencies of protein binding inferred from omission
      reconstitution experiments are thought to preclude certain assembly pathways and
      thus enforce ordered assembly, but this concept is at odds with kinetic data
      suggesting a more parallel assembly landscape. A major challenge is deconvolution
      of the statistical distribution of intermediates that are populated during
      assembly at high concentrations approaching in vivo assembly conditions. To
      specifically resolve the intermediates formed by binding of three ribosomal
      proteins to the full length 16S rRNA, we introduce Fluorescence Triple
      Correlation Spectroscopy (F3CS). F3CS identifies specific ternary complexes by
      detecting coincident fluctuations in three-color fluorescence data. Triple
      correlation integrals quantify concentrations and diffusion kinetics of triply
      labeled species, and F3CS data can be fit alongside auto-correlation and cross
      correlation data to quantify the populations of 10 specific ribosome assembly
      intermediates. The distribution of intermediates generated by binding three
      ribosomal proteins to the entire native 16S rRNA included significant populations
      of species that were not previously thought to be thermodynamically accessible,
      questioning the current interpretation of the classic omission-reconstitution
      experiments. F3CS is a general approach for analyzing assembly and function of
      macromolecular complexes, especially those too large for traditional biophysical
      methods.

PMID- 22869700
TI  - Assembly and subunit stoichiometry of the functional helicase-primase (primosome)
      complex of bacteriophage T4.
AB  - Physical biochemical techniques are used to establish the structure, subunit
      stoichiometry, and assembly pathway of the primosome complex of the bacteriophage
      T4 DNA replication system. Analytical ultracentrifugation and fluorescence
      anisotropy methods show that the functional T4 primosome consists of six gp41
      helicase subunits that assemble into a hexagon, driven by the binding of six NTPs
      (or six nonhydrolyzable GTPgammaS analogues) that are located at and stabilize
      the intersubunit interfaces, together with a single tightly bound gp61 primase
      subunit. Assembling the components of the primosome onto a model DNA replication
      fork is a multistep process, but equilibrium cannot be reached along all mixing
      pathways. Producing a functional complex requires that the helicase hexamer be
      assembled in the presence of the DNA replication fork construct prior to the
      addition of the primase to avoid the formation of metastable DNA-protein
      aggregates. The gp41 helicase hexamer binds weakly to fork DNA in the absence of
      primase, but forms a much more stable primosome complex that expresses full and
      functional helicase (and primase) activities when bound to a gp61 primase subunit
      at a helicase:primase subunit ratio of 61. The presence of additional primase
      subunits does not change the molecular mass or helicase activity of the
      primosome, but significantly inhibits its primase activity. We develop both an
      assembly pathway and a minimal mechanistic model for the structure and function
      of the T4 primosome that are likely to be relevant to the assembly and function
      of the replication primosome subassemblies of higher organisms as well.

PMID- 22869701
TI  - Two-year survey comparing earthquake activity and injection-well locations in the
      Barnett Shale, Texas.
AB  - Between November 2009 and September 2011, temporary seismographs deployed under
      the EarthScope USArray program were situated on a 70-km grid covering the Barnett
      Shale in Texas, recording data that allowed sensing and locating regional
      earthquakes with magnitudes 1.5 and larger. I analyzed these data and located 67
      earthquakes, more than eight times as many as reported by the National Earthquake
      Information Center. All 24 of the most reliably located epicenters occurred in
      eight groups within 3.2 km of one or more injection wells. These included wells
      near Dallas-Fort Worth and Cleburne, Texas, where earthquakes near injection
      wells were reported by the media in 2008 and 2009, as well as wells in six other
      locations, including several where no earthquakes have been reported previously.
      This suggests injection-triggered earthquakes are more common than is generally
      recognized. All the wells nearest to the earthquake groups reported maximum
      monthly injection rates exceeding 150,000 barrels of water per month (24,000
      m(3)/mo) since October 2006. However, while 9 of 27 such wells in Johnson County
      were near earthquakes, elsewhere no earthquakes occurred near wells with similar
      injection rates. A plausible hypothesis to explain these observations is that
      injection only triggers earthquakes if injected fluids reach and relieve friction
      on a suitably oriented, nearby fault that is experiencing regional tectonic
      stress. Testing this hypothesis would require identifying geographic regions
      where there is interpreted subsurface structure information available to
      determine whether there are faults near seismically active and seismically
      quiescent injection wells.

PMID- 22869702
TI  - Long-range exciton dissociation in organic solar cells.
AB  - It is normally assumed that electrons and holes in organic solar cells are
      generated by the dissociation of excitons at the interface between donor and
      acceptor materials in strongly bound hole-electron pairs. We show in this
      contribution that excitons can dissociate tens of angstroms away from the
      interface and generate partially separated electrons and holes, which can more
      easily overcome their coulombic attraction and form free charges. We first
      establish under what conditions long-range exciton dissociation is likely (using
      a kinetic model and a microscopic model for the calculation of the long-range
      electron transfer rate). Then, defining a rather general model Hamiltonian for
      the donor material, we show that the phenomenon is extremely common in the
      majority of polymer:fullerene bulk heterojunction solar cells.

PMID- 22869703
TI  - How an interacting many-body system tunnels through a potential barrier to open
      space.
AB  - The tunneling process in a many-body system is a phenomenon which lies at the
      very heart of quantum mechanics. It appears in nature in the form of alpha-decay,
      fusion and fission in nuclear physics, and photoassociation and photodissociation
      in biology and chemistry. A detailed theoretical description of the decay process
      in these systems is a very cumbersome problem, either because of very complicated
      or even unknown interparticle interactions or due to a large number of
      constituent particles. In this work, we theoretically study the phenomenon of
      quantum many-body tunneling in a transparent and controllable physical system, an
      ultracold atomic gas. We analyze a full, numerically exact many-body solution of
      the Schrodinger equation of a one-dimensional system with repulsive interactions
      tunneling to open space. We show how the emitted particles dissociate or fragment
      from the trapped and coherent source of bosons: The overall many-particle decay
      process is a quantum interference of single-particle tunneling processes emerging
      from sources with different particle numbers taking place simultaneously. The
      close relation to atom lasers and ionization processes allows us to unveil the
      great relevance of many-body correlations between the emitted and trapped
      fractions of the wave function in the respective processes.

PMID- 22869704
TI  - Atomic structure of the vimentin central alpha-helical domain and its
      implications for intermediate filament assembly.
AB  - Together with actin filaments and microtubules, intermediate filaments (IFs) are
      the basic cytoskeletal components of metazoan cells. Over 80 human diseases have
      been linked to mutations in various IF proteins to date. However, the filament
      structure is far from being resolved at the atomic level, which hampers rational
      understanding of IF pathologies. The elementary building block of all IF proteins
      is a dimer consisting of an alpha-helical coiled-coil (CC) "rod" domain flanked
      by the flexible head and tail domains. Here we present three crystal structures
      of overlapping human vimentin fragments that comprise the first half of its rod
      domain. Given the previously solved fragments, a nearly complete atomic structure
      of the vimentin rod has become available. It consists of three alpha-helical
      segments (coils 1A, 1B, and 2) interconnected by linkers (L1 and L12). Most of
      the CC structure has a left-handed twist with heptad repeats, but both coil 1B
      and coil 2 also exhibit untwisted, parallel stretches with hendecad repeats. In
      the crystal structure, linker L1 was found to be alpha-helical without being
      involved in the CC formation. The available data allow us to construct an atomic
      model of the antiparallel tetramer representing the second level of vimentin
      assembly. Although the presence of the nonhelical head domains is essential for
      proper tetramer stabilization, the precise alignment of the dimers forming the
      tetramer appears to depend on the complementarity of their surface charge
      distribution patterns, while the structural plasticity of linker L1 and coil 1A
      plays a role in the subsequent IF assembly process.

PMID- 22869705
TI  - Structures of dolomite at ultrahigh pressure and their influence on the deep
      carbon cycle.
AB  - Carbon-bearing solids, fluids, and melts in the Earth's deep interior may play an
      important role in the long-term carbon cycle. Here we apply synchrotron X-ray
      single crystal micro-diffraction techniques to identify and characterize the high
      pressure polymorphs of dolomite. Dolomite-II, observed above 17 GPa, is
      triclinic, and its structure is topologically related to CaCO(3)-II. It
      transforms above 35 GPa to dolomite-III, also triclinic, which features carbon in
      [3 + 1] coordination at the highest pressures investigated (60 GPa). The
      structure is therefore representative of an intermediate between the low-pressure
      carbonates and the predicted ultra-high pressure carbonates, with carbon in
      tetrahedral coordination. Dolomite-III does not decompose up to the melting point
      (2,600 K at 43 GPa) and its thermodynamic stability demonstrates that this
      complex phase can transport carbon to depths of at least up to 1,700 km. Dolomite
      III, therefore, is a likely occurring phase in areas containing recycled crustal
      slabs, which are more oxidized and Ca-enriched than the primitive lower mantle.
      Indeed, these phases may play an important role as carbon carriers in the whole
      mantle carbon cycling. As such, they are expected to participate in the
      fundamental petrological processes which, through carbon-bearing fluids and
      carbonate melts, will return carbon back to the Earth's surface.

PMID- 22869706
TI  - Electron spin resonance of nitrogen-vacancy centers in optically trapped
      nanodiamonds.
AB  - Using an optical tweezers apparatus, we demonstrate three-dimensional control of
      nanodiamonds in solution with simultaneous readout of ground-state electron-spin
      resonance (ESR) transitions in an ensemble of diamond nitrogen-vacancy color
      centers. Despite the motion and random orientation of nitrogen-vacancy centers
      suspended in the optical trap, we observe distinct peaks in the measured ESR
      spectra qualitatively similar to the same measurement in bulk. Accounting for the
      random dynamics, we model the ESR spectra observed in an externally applied
      magnetic field to enable dc magnetometry in solution. We estimate the dc magnetic
      field sensitivity based on variations in ESR line shapes to be approximately 50
      MUT/?Hz. This technique may provide a pathway for spin-based magnetic, electric,
      and thermal sensing in fluidic environments and biophysical systems inaccessible
      to existing scanning probe techniques.

PMID- 22869707
TI  - Perception of climate change.
AB  - "Climate dice," describing the chance of unusually warm or cool seasons, have
      become more and more "loaded" in the past 30 y, coincident with rapid global
      warming. The distribution of seasonal mean temperature anomalies has shifted
      toward higher temperatures and the range of anomalies has increased. An important
      change is the emergence of a category of summertime extremely hot outliers, more
      than three standard deviations (3sigma) warmer than the climatology of the 1951
      1980 base period. This hot extreme, which covered much less than 1% of Earth's
      surface during the base period, now typically covers about 10% of the land area.
      It follows that we can state, with a high degree of confidence, that extreme
      anomalies such as those in Texas and Oklahoma in 2011 and Moscow in 2010 were a
      consequence of global warming because their likelihood in the absence of global
      warming was exceedingly small. We discuss practical implications of this
      substantial, growing, climate change.

PMID- 22869708
TI  - Structural insights into neuronal K+ channel-calmodulin complexes.
AB  - Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds
      to and modulates a wide variety of ion channels. Despite the large repository of
      high-resolution structures of CaM bound to peptide fragments derived from ion
      channels, there is no structural information about CaM bound to a fully folded
      ion channel at the plasma membrane. To determine the location of CaM docked to a
      functioning KCNQ K(+) channel, we developed an intracellular tethered blocker
      approach to measure distances between CaM residues and the ion-conducting
      pathway. Combining these distance restraints with structural bioinformatics, we
      generated an archetypal quaternary structural model of an ion channel-CaM complex
      in the open state. These models place CaM close to the cytoplasmic gate, where it
      is well positioned to modulate channel function.

PMID- 22869709
TI  - Influenza virus binds its host cell using multiple dynamic interactions.
AB  - Influenza virus belongs to a wide range of enveloped viruses. The major spike
      protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids
      with dissociation constants in the millimolar range [Sauter NK, et al. (1992)
      Biochemistry 31:9609-9621], indicating a multivalent binding mode. Here, we
      characterized the attachment of influenza virus to host cell receptors using
      three independent approaches. Optical tweezers and atomic force microscopy-based
      single-molecule force spectroscopy revealed very low interaction forces. Further,
      the observation of sequential unbinding events strongly suggests a multivalent
      binding mode between virus and cell membrane. Molecular dynamics simulations
      reveal a variety of unbinding pathways that indicate a highly dynamic interaction
      between HA and its receptor, allowing rationalization of influenza virus-cell
      binding quantitatively at the molecular level.

PMID- 22869710
TI  - First-order rate-determining aggregation mechanism of p53 and its implications.
AB  - Aggregation of p53 is initiated by first-order processes that generate an
      aggregation-prone state with parallel pathways of major or partial unfolding.
      Here, we elaborate the mechanism and explore its consequences, beginning with the
      core domain and extending to the full-length p53 mutant Y220C. Production of
      large light-scattering particles was slower than formation of the Thioflavin T
      binding state and simultaneous depletion of monomer. EDTA removes Zn(2+) to
      generate apo-p53, which aggregated faster than holo-p53. Apo-Y220C also
      aggregated by both partial and major unfolding. Apo-p53 was not an obligatory
      intermediate in the aggregation of holo-p53, but affords a parallel pathway that
      may be relevant to oncogenic mutants with impaired Zn(2+) binding. Full-length
      tetrameric Y220C formed the Thioflavin T-binding state with similar rate
      constants to those of core domain, consistent with a unimolecular initiation that
      is unaffected by neighboring subunits, but very slowly formed small light
      scattering particles. Apo-Y220C and aggregated holo-Y220C had little, if any,
      seeding effect on the initial polymerization of holo-Y220C (measured by
      Thioflavin T binding), consistent with initiation being a unimolecular process.
      But apo-Y220C and aggregated holo-Y220C accelerated somewhat the subsequent
      formation of light-scattering particles from holo-protein, implying
      coaggregation. The implications for cancer cells containing wild-type and
      unstable mutant alleles are that aggregation of wild-type p53 (or homologs) might
      not be seeded by aggregated mutant, but it could coaggregate with p53 or other
      cellular proteins that have undergone the first steps of aggregation and speed up
      the formation of microscopically observable aggregates.

PMID- 22869711
TI  - A search for thermal excursions from ancient extraterrestrial impacts using
      Hadean zircon Ti-U-Th-Pb depth profiles.
AB  - Few terrestrial localities preserve more than a trace lithic record prior to ca.
      3.8 Ga greatly limiting our understanding of the first 700 Ma of Earth history, a
      period inferred to have included a spike in the bolide flux to the inner solar
      system at ca. 3.85-3.95 Ga (the Late Heavy Bombardment, LHB). An accessible
      record of this era may be found in Hadean detrital zircons from the Jack Hills,
      Western Australia, in the form of MUm-scale epitaxial overgrowths. By comparing
      crystallization temperatures of pre-3.8 Ga zircon overgrowths to the archive of
      zircon temperature spectra, it should, in principle, be possible to identify a
      distinctive impact signature. We have developed Ti-U-Th-Pb ion microprobe depth
      profiling to obtain age and temperature information within these zircon
      overgrowths and undertaken a feasibility study of its possible use in identifying
      impact events. Of eight grains profiled in this fashion, four have overgrowths of
      LHB-era age. Age vs. temperature profiles reveal a period between ca. 3.85-3.95
      Ga (i.e., LHB era) characterized by significantly higher temperatures
      (approximately 840-875  degrees C) than do older or younger zircons or zircon
      domains (approximately 630-750  degrees C). However, temperatures approaching 900
      degrees C can result in Pb isotopic exchange rendering interpretation of these
      profiles nonunique. Coupled age-temperature depth profiling shows promise in this
      role, and the preliminary data we report could represent the first terrestrial
      evidence for impact-related heating during the LHB.

PMID- 22869712
TI  - Interpreting the widespread nonlinear force spectra of intermolecular bonds.
AB  - Single molecule force spectroscopy probes the strength, lifetime, and energetic
      details of intermolecular interactions in a simple experiment. A growing number
      of these studies have reported distinctly nonlinear trends in rupture force with
      loading rate that are typically explained in conventional models by invoking
      complex escape pathways. Recent analyses suggested that these trends should be
      expected even for simple barriers based on the basic assumptions of bond rupture
      dynamics and thus may represent the norm rather than the exception. Here we
      explore how these nonlinear trends reflect the two fundamental regimes of bond
      rupture: (i) a near-equilibrium regime, produced either by bond reforming in the
      case of a single bond or by asynchronized rupture of multiple individual bonds,
      and (ii) a kinetic regime produced by fast, non-equilibrium bond rupture. We
      analyze both single- and multi-bonded cases, describe the full evolution of the
      system as it transitions between near- and far-from-equilibrium loading regimes,
      and show that both interpretations produce essentially identical force spectra.
      Data from 10 different molecular systems show that this model provides a
      comprehensive description of force spectra for a diverse suite of bonds over
      experimentally relevant loading rates, removes the inconsistencies of previous
      interpretations of transition state distances, and gives ready access to both
      kinetic and thermodynamic information about the interaction. These results imply
      that single-molecule binding free energies for a vast number of bonds have
      already been measured.

PMID- 22869713
TI  - Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition.
AB  - Aggregation of destabilized mutants of the tumor suppressor p53 is a major route
      for its loss of activity. In order to assay drugs that inhibit aggregation of
      p53, we established the basic kinetics of aggregation of its core domain, using
      the mutant Y220C that has a mutation-induced, druggable cavity. Aggregation
      monitored by light scattering followed lag kinetics. Electron microscopy revealed
      the formation of small aggregates that subsequently grew to larger amorphous
      aggregates. The kinetics of aggregation produced surprising results: progress
      curves followed either by the binding of Thioflavin T or the fluorescence of the
      protein at 340 nm fitted well to simple two-step sequential first-order lag
      kinetics with rate constants k(1) and k(2) that were independent of protein
      concentration, and not to classical nucleation-growth. We suggest a mechanism of
      first-order formation of an aggregation competent state as being rate determining
      followed by rapid polymerization with the higher order kinetics. By measuring the
      inhibition kinetics of k(1) and k(2), we resolved that the process with the
      higher rate constant followed that of the lower. Further, there was only partial
      inhibition of k(1) and k(2), which showed two parallel pathways of aggregation,
      one via a state that requires unfolding of the protein and the other of partial
      unfolding with the ligand still bound. Inhibition kinetics of ligands provides a
      useful tool for probing an aggregation mechanism.

PMID- 22869714
TI  - Aging of biogenic secondary organic aerosol via gas-phase OH radical reactions.
AB  - The Multiple Chamber Aerosol Chemical Aging Study (MUCHACHAS) tested the
      hypothesis that hydroxyl radical (OH) aging significantly increases the
      concentration of first-generation biogenic secondary organic aerosol (SOA). OH is
      the dominant atmospheric oxidant, and MUCHACHAS employed environmental chambers
      of very different designs, using multiple OH sources to explore a range of
      chemical conditions and potential sources of systematic error. We isolated the
      effect of OH aging, confirming our hypothesis while observing corresponding
      changes in SOA properties. The mass increases are consistent with an existing gap
      between global SOA sources and those predicted in models, and can be described by
      a mechanism suitable for implementation in those models.

PMID- 22869716
TI  - North African Jewish and non-Jewish populations form distinctive, orthogonal
      clusters.
AB  - North African Jews constitute the second largest Jewish Diaspora group. However,
      their relatedness to each other; to European, Middle Eastern, and other Jewish
      Diaspora groups; and to their former North African non-Jewish neighbors has not
      been well defined. Here, genome-wide analysis of five North African Jewish groups
      (Moroccan, Algerian, Tunisian, Djerban, and Libyan) and comparison with other
      Jewish and non-Jewish groups demonstrated distinctive North African Jewish
      population clusters with proximity to other Jewish populations and variable
      degrees of Middle Eastern, European, and North African admixture. Two major
      subgroups were identified by principal component, neighbor joining tree, and
      identity-by-descent analysis-Moroccan/Algerian and Djerban/Libyan-that varied in
      their degree of European admixture. These populations showed a high degree of
      endogamy and were part of a larger Ashkenazi and Sephardic Jewish group. By
      principal component analysis, these North African groups were orthogonal to
      contemporary populations from North and South Morocco, Western Sahara, Tunisia,
      Libya, and Egypt. Thus, this study is compatible with the history of North
      African Jews-founding during Classical Antiquity with proselytism of local
      populations, followed by genetic isolation with the rise of Christianity and then
      Islam, and admixture following the emigration of Sephardic Jews during the
      Inquisition.

PMID- 22869717
TI  - Postsynaptic dysfunction is associated with spatial and object recognition memory
      loss in a natural model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated
      with progressive memory loss, severe dementia, and hallmark neuropathological
      markers, such as deposition of amyloid-beta (Abeta) peptides in senile plaques
      and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles.
      Recent evidence obtained from transgenic mouse models suggests that soluble,
      nonfibrillar Abeta oligomers may induce synaptic failure early in AD. Despite
      their undoubted value, these transgenic models rely on genetic manipulations that
      represent the inherited and familial, but not the most abundant, sporadic form of
      AD. A nontransgenic animal model that still develops hallmarks of AD would be an
      important step toward understanding how sporadic AD is initiated. Here we show
      that starting between 12 and 36 mo of age, the rodent Octodon degus naturally
      develops neuropathological signs of AD, such as accumulation of Abeta oligomers
      and phosphorylated tau proteins. Moreover, age-related changes in Abeta oligomers
      and tau phosphorylation levels are correlated with decreases in spatial and
      object recognition memory, postsynaptic function, and synaptic plasticity. These
      findings validate O. degus as a suitable natural model for studying how sporadic
      AD may be initiated.

PMID- 22869719
TI  - A paradoxical teratogenic mechanism for retinoic acid.
AB  - Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles
      in mammalian embryogenesis. Nevertheless, it has long been recognized that
      overexposure to vitamin A or retinoic acid causes widespread teratogenesis in
      rodents as well as humans. Although it has a short half-life, exposure to high
      levels of retinoic acid can disrupt development of yet-to-be formed organs,
      including the metanephros, the embryonic organ which normally differentiates into
      the mature kidney. Paradoxically, it is known that either an excess or a
      deficiency of retinoic acid results in similar malformations in some organs,
      including the mammalian kidney. Accordingly, we hypothesized that excess retinoic
      acid is teratogenic by inducing a longer lasting, local retinoic acid deficiency.
      This idea was tested in an established in vivo mouse model in which exposure to
      excess retinoic acid well before metanephric rudiments exist leads to failure of
      kidney formation several days later. Results showed that teratogen exposure was
      followed by decreased levels of Raldh transcripts encoding retinoic acid
      synthesizing enzymes and increased levels of Cyp26a1 and Cyp26b1 mRNAs encoding
      enzymes that catabolize retinoic acid. Concomitantly, there was significant
      reduction in retinoic acid levels in whole embryos and kidney rudiments.
      Restoration of retinoic acid levels by maternal supplementation with low doses of
      retinoic acid following the teratogenic insult rescued metanephric kidney
      development and abrogated several extrarenal developmental defects. This
      previously undescribed and unsuspected mechanism provides insight into the
      molecular pathway of retinoic acid-induced teratogenesis.

PMID- 22869720
TI  - MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate
      metabolism in pancreatic cancer.
AB  - Aberrant glucose metabolism is one of the hallmarks of cancer that facilitates
      cancer cell survival and proliferation. Here, we demonstrate that MUC1, a large,
      type I transmembrane protein that is overexpressed in several carcinomas
      including pancreatic adenocarcinoma, modulates cancer cell metabolism to
      facilitate growth properties of cancer cells. MUC1 occupies the promoter elements
      of multiple genes directly involved in glucose metabolism and regulates their
      expression. Furthermore, MUC1 expression enhances glycolytic activity in
      pancreatic cancer cells. We also demonstrate that MUC1 expression enhances in
      vivo glucose uptake and expression of genes involved in glucose uptake and
      metabolism in orthotopic implantation models of pancreatic cancer. The MUC1
      cytoplasmic tail is known to activate multiple signaling pathways through its
      interactions with several transcription factors/coregulators at the promoter
      elements of various genes. Our results indicate that MUC1 acts as a modulator of
      the hypoxic response in pancreatic cancer cells by regulating the
      expression/stability and activity of hypoxia-inducible factor-1alpha (HIF
      1alpha). MUC1 physically interacts with HIF-1alpha and p300 and stabilizes the
      former at the protein level. By using a ChIP assay, we demonstrate that MUC1
      facilitates recruitment of HIF-1alpha and p300 on glycolytic gene promoters in a
      hypoxia-dependent manner. Also, by metabolomic studies, we demonstrate that MUC1
      regulates multiple metabolite intermediates in the glucose and amino acid
      metabolic pathways. Thus, our studies indicate that MUC1 acts as a master
      regulator of the metabolic program and facilitates metabolic alterations in the
      hypoxic environments that help tumor cells survive and proliferate under such
      conditions.

PMID- 22869718
TI  - Hydrogen-limited growth of hyperthermophilic methanogens at deep-sea hydrothermal
      vents.
AB  - Microbial productivity at hydrothermal vents is among the highest found anywhere
      in the deep ocean, but constraints on microbial growth and metabolism at vents
      are lacking. We used a combination of cultivation, molecular, and geochemical
      tools to verify pure culture H(2) threshold measurements for hyperthermophilic
      methanogenesis in low-temperature hydrothermal fluids from Axial Volcano and
      Endeavour Segment in the northeastern Pacific Ocean. Two Methanocaldococcus
      strains from Axial and Methanocaldococcus jannaschii showed similar Monod growth
      kinetics when grown in a bioreactor at varying H(2) concentrations. Their H(2)
      half-saturation value was 66 MUM, and growth ceased below 17-23 MUM H(2), 10-fold
      lower than previously predicted. By comparison, measured H(2) and CH(4)
      concentrations in fluids suggest that there was generally sufficient H(2) for
      Methanocaldococcus growth at Axial but not at Endeavour. Fluids from one vent at
      Axial (Marker 113) had anomalously high CH(4) concentrations and contained
      various thermal classes of methanogens based on cultivation and mcrA/mrtA
      analyses. At Endeavour, methanogens were largely undetectable in fluid samples
      based on cultivation and molecular screens, although abundances of
      hyperthermophilic heterotrophs were relatively high. Where present,
      Methanocaldococcus genes were the predominant mcrA/mrtA sequences recovered and
      comprised ~0.2-6% of the total archaeal community. Field and coculture data
      suggest that H(2) limitation may be partly ameliorated by H(2) syntrophy with
      hyperthermophilic heterotrophs. These data support our estimated H(2) threshold
      for hyperthermophilic methanogenesis at vents and highlight the need for coupled
      laboratory and field measurements to constrain microbial distribution and
      biogeochemical impacts in the deep sea.

PMID- 22869721
TI  - RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5
      bisphosphate.
AB  - Caenorhabditis elegans RAB-10 and mammalian Rab10 are key regulators of endocytic
      recycling, especially in the basolateral recycling pathways of polarized
      epithelial cells. To understand better how RAB-10 contributes to recycling
      endosome function, we sought to identify RAB-10 effectors. One RAB-10-binding
      partner that we identified, CNT-1, is the only C. elegans homolog of the
      mammalian Arf6 GTPase-activating proteins ACAP1 and ACAP2. Arf6 is known to
      regulate endosome-to-plasma membrane transport, in part through activation of
      type I phophatidylinositol-4-phosphate 5 kinase. Here we show that CNT-1 binds to
      RAB-10 through its C-terminal ankyrin repeats and colocalizes with RAB-10 and ARF
      6 on recycling endosomes in vivo. Furthermore, we find that RAB-10 is required
      for the recruitment of CNT-1 to endosomal membranes in the intestinal epithelium.
      Consistent with negative regulation of ARF-6 by RAB-10 and CNT-1, we found
      overaccumulation of endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]
      in cnt-1 and rab-10 mutants and reduced endosomal PI(4,5)P2 levels in arf-6
      mutants. These mutants produced similar effects on endosomal recruitment of the
      PI(4,5)P2-dependent membrane-bending proteins RME-1/Ehd and SDPN
      1/Syndapin/Pacsin and resulted in endosomal trapping of specific recycling cargo.
      Our studies identify a RAB-10-to-ARF-6 regulatory loop required to regulate
      endosomal PI(4,5)P2, a key phosphoinositide in membrane traffic.

PMID- 22869722
TI  - Cultural transmission of social essentialism.
AB  - Social essentialism entails the belief that certain social categories (e.g.,
      gender, race) mark fundamentally distinct kinds of people. Essentialist beliefs
      have pernicious consequences, supporting social stereotyping and contributing to
      prejudice. How does social essentialism develop? In the studies reported here, we
      tested the hypothesis that generic language facilitates the cultural transmission
      of social essentialism. Two studies found that hearing generic language about a
      novel social category diverse for race, ethnicity, age, and sex led 4-y-olds and
      adults to develop essentialist beliefs about that social category. A third study
      documented that experimentally inducing parents to hold essentialist beliefs
      about a novel social category led them to produce more generic language when
      discussing the category with their children. Thus, generic language facilitates
      the transmission of essentialist beliefs about social categories from parents to
      children.

PMID- 22869723
TI  - Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense
      delivery.
AB  - Duchenne muscular dystrophy (DMD), the commonest form of muscular dystrophy, is
      caused by lack of dystrophin. One of the most promising therapeutic approaches is
      antisense-mediated elimination of frame-disrupting mutations by exon skipping.
      However, this approach faces two major hurdles: limited applicability of each
      individual target exon and uncertain function and stability of each resulting
      truncated dystrophin. Skipping of exons 45-55 at the mutation hotspot of the DMD
      gene would address both issues. Theoretically it could rescue more than 60% of
      patients with deletion mutations. Moreover, spontaneous deletions of this
      specific region are associated with asymptomatic or exceptionally mild
      phenotypes. However, such multiple exon skipping of exons 45-55 has proved
      technically challenging. We have therefore designed antisense oligo (AO)
      morpholino mixtures to minimize self- or heteroduplex formation. These were
      tested as conjugates with cell-penetrating moieties (vivo-morpholinos). We have
      tested the feasibility of skipping exons 45-55 in H2K-mdx52 myotubes and in mdx52
      mice, which lack exon 52. Encouragingly, with mixtures of 10 AOs, we demonstrated
      skipping of all 10 exons in vitro, in H2K-mdx52 myotubes and on intramuscular
      injection into mdx52 mice. Moreover, in mdx52 mice in vivo, systemic injections
      of 10 AOs induced extensive dystrophin expression at the subsarcolemma in
      skeletal muscles throughout the body, producing up to 15% of wild-type dystrophin
      protein levels, accompanied by improved muscle strength and histopathology
      without any detectable toxicity. This is a unique successful demonstration of
      effective rescue by exon 45-55 skipping in a dystrophin-deficient animal model.

PMID- 22869724
TI  - Dysfunction of the auditory thalamus in developmental dyslexia.
AB  - Developmental dyslexia, a severe and persistent reading and spelling impairment,
      is characterized by difficulties in processing speech sounds (i.e., phonemes).
      Here, we test the hypothesis that these phonological difficulties are associated
      with a dysfunction of the auditory sensory thalamus, the medial geniculate body
      (MGB). By using functional MRI, we found that, in dyslexic adults, the MGB
      responded abnormally when the task required attending to phonemes compared with
      other speech features. No other structure in the auditory pathway showed distinct
      functional neural patterns between the two tasks for dyslexic and control
      participants. Furthermore, MGB activity correlated with dyslexia diagnostic
      scores, indicating that the task modulation of the MGB is critical for
      performance in dyslexics. These results suggest that deficits in dyslexia are
      associated with a failure of the neural mechanism that dynamically tunes MGB
      according to predictions from cortical areas to optimize speech processing. This
      view on task-related MGB dysfunction in dyslexics has the potential to reconcile
      influential theories of dyslexia within a predictive coding framework of brain
      function.

PMID- 22869725
TI  - IgG1+ ovalbumin-specific B-cell transnuclear mice show class switch recombination
      in rare allelically included B cells.
AB  - We used somatic cell nuclear transfer (SCNT) to generate a mouse from the nucleus
      of an IgG1(+) ovalbumin-specific B cell. The resulting OBI mice show generally
      normal B-cell development, with elevated percentages of marginal zone B cells and
      a reduction in B-1 B cells. Whereas OBI RAG1(-/-) mice have exclusively IgG1 anti
      ovalbumin in their serum, OBI mice show elevated levels of anti-ovalbumin of
      nearly all isotypes 3' of the gamma1 constant region in the IgH locus, indicating
      that class switch recombination (CSR) occurs in the absence of immunization with
      ovalbumin. This CSR is associated with the presence of IgM(+)IgG1(+) double
      producer B cells that represent <1% of total B cells, accumulate in the
      peritoneal cavity, and account for near-normal levels of serum IgM and IgG3.

PMID- 22869726
TI  - General and inducible hypermutation facilitate parallel adaptation in Pseudomonas
      aeruginosa despite divergent mutation spectra.
AB  - The successful growth of hypermutator strains of bacteria contradicts a clear
      preference for lower mutation rates observed in the microbial world. Whether by
      general DNA repair deficiency or the inducible action of low-fidelity DNA
      polymerases, the evolutionary strategies of bacteria include methods of
      hypermutation. Although both raise mutation rate, general and inducible
      hypermutation operate through distinct molecular mechanisms and therefore likely
      impart unique adaptive consequences. Here we compare the influence of general and
      inducible hypermutation on adaptation in the model organism Pseudomonas
      aeruginosa PAO1 through experimental evolution. We observed divergent spectra of
      single base substitutions derived from general and inducible hypermutation by
      sequencing rpoB in spontaneous rifampicin-resistant (Rif(R)) mutants. Likewise,
      the pattern of mutation in a draft genome sequence of a derived inducible
      hypermutator isolate differed from those of general hypermutators reported in the
      literature. However, following experimental evolution, populations of both
      mutator types exhibited comparable improvements in fitness across varied
      conditions that differed from the highly specific adaptation of nonmutators. Our
      results suggest that despite their unique mutation spectra, general and inducible
      hypermutation can analogously influence the ecology and adaptation of bacteria,
      significantly shaping pathogenic populations where hypermutation has been most
      widely observed.

PMID- 22869727
TI  - Protection from the acquisition of Staphylococcus aureus nasal carriage by cross
      reactive antibody to a pneumococcal dehydrogenase.
AB  - Nasal colonization by Staphylococcus aureus is the major risk factor for disease
      and transmission. Epidemiological studies have reported a reduced risk of S.
      aureus carriage in immunocompetent but not in immunocompromised children
      colonized by Streptococcus pneumoniae. We investigate the hypothesis that the
      immune response to pneumococcal colonization affects S. aureus colonization. We
      demonstrate that pneumococcal colonization in mice inhibits subsequent S. aureus
      acquisition in an antibody-dependent manner and elicits antibody that cross
      reacts with S. aureus. We identify the staphylococcal target of cross-reactive
      antibody as 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), and the homologous
      immunogen in S. pneumoniae as SP_1119, both of which are conserved
      dehydrogenases. These antigens are necessary and sufficient to inhibit the
      acquisition of S. aureus colonization in a mouse model. Our findings demonstrate
      that immune-mediated cross-reactivity between S. pneumoniae and S. aureus
      protects against S. aureus nasal acquisition and thus reveal a paradigm for
      identifying protective antigens against S. aureus.

PMID- 22869728
TI  - Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in
      mice.
AB  - Prion diseases are fatal neurodegenerative disorders that include bovine
      spongiform encephalopathy (BSE) and scrapie in animals and Creutzfeldt-Jakob
      disease (CJD) in humans. They are characterized by long incubation periods,
      variation in which is determined by many factors including genetic background. In
      some cases it is possible that incubation time may be directly correlated to the
      level of gene expression. To test this hypothesis, we combined incubation time
      data from five different inbred lines of mice with quantitative gene expression
      profiling in normal brains and identified five genes with expression levels that
      correlate with incubation time. One of these genes, Hspa13 (Stch), is a member of
      the Hsp70 family of ATPase heat shock proteins, which have been previously
      implicated in prion propagation. To test whether Hspa13 plays a causal role in
      determining the incubation period, we tested two overexpressing mouse models. The
      Tc1 human chromosome 21 (Hsa21) transchromosomic mouse model of Down syndrome is
      trisomic for many Hsa21 genes including Hspa13 and following Chandler/Rocky
      Mountain Laboratory (RML) prion inoculation, shows a 4% reduction in incubation
      time. Furthermore, a transgenic model with eightfold overexpression of mouse
      Hspa13 exhibited highly significant reductions in incubation time of 16, 15, and
      7% following infection with Chandler/RML, ME7, and MRC2 prion strains,
      respectively. These data further implicate Hsp70-like molecular chaperones in
      protein misfolding disorders such as prion disease.

PMID- 22869730
TI  - Interkingdom metabolic transformations captured by microbial imaging mass
      spectrometry.
AB  - In polymicrobial infections, microbes can interact with both the host immune
      system and one another through direct contact or the secretion of metabolites,
      affecting disease progression and treatment options. The thick mucus in the lungs
      of patients with cystic fibrosis is highly susceptible to polymicrobial
      infections by opportunistic pathogens, including the bacterium Pseudomonas
      aeruginosa and the fungus Aspergillus fumigatus. Unravelling the hidden molecular
      interactions within such polymicrobial communities and their metabolic exchange
      processes will require effective enabling technologies applied to model systems.
      In the present study, MALDI-TOF and MALDI-FT-ICR imaging mass spectrometry (MALDI
      IMS) combined with MS/MS networking were used to provide insight into the
      interkingdom interaction between P. aeruginosa and A. fumigatus at the molecular
      level. The combination of these technologies enabled the visualization and
      identification of metabolites secreted by these microorganisms grown on agar. A
      complex molecular interplay was revealed involving suppression, increased
      production, and biotransformation of a range of metabolites. Of particular
      interest is the observation that P. aeruginosa phenazine metabolites were
      converted by A. fumigatus into other chemical entities with alternative
      properties, including enhanced toxicities and the ability to induce fungal
      siderophores. This work highlights the capabilities of MALDI-IMS and MS/MS
      network analysis to study interkingdom interactions and provides insight into the
      complex nature of polymicrobial metabolic exchange and biotransformations.

PMID- 22869729
TI  - ERK1/2 activation is a therapeutic target in age-related macular degeneration.
AB  - Deficient expression of the RNase III DICER1, which leads to the accumulation of
      cytotoxic Alu RNA, has been implicated in degeneration of the retinal pigmented
      epithelium (RPE) in geographic atrophy (GA), a late stage of age-related macular
      degeneration that causes blindness in millions of people worldwide. Here we show
      increased extracellular-signal-regulated kinase (ERK) 1/2 phosphorylation in the
      RPE of human eyes with GA and that RPE degeneration in mouse eyes and in human
      cell culture induced by DICER1 depletion or Alu RNA exposure is mediated via
      ERK1/2 signaling. Alu RNA overexpression or DICER1 knockdown increases ERK1/2
      phosphorylation in the RPE in mice and in human cell culture. Alu RNA-induced RPE
      degeneration in mice is rescued by intravitreous administration of PD98059, an
      inhibitor of the ERK1/2-activating kinase MEK1, but not by inhibitors of other
      MAP kinases such as p38 or JNK. These findings reveal a previously unrecognized
      function of ERK1/2 in the pathogenesis of GA and provide a mechanistic basis for
      evaluation of ERK1/2 inhibition in treatment of this disease.

PMID- 22869731
TI  - Strategies to alleviate original antigenic sin responses to influenza viruses.
AB  - Original antigenic sin is a phenomenon wherein sequential exposure to closely
      related influenza virus variants reduces antibody (Ab) response to novel
      antigenic determinants in the second strain and, consequently, impairs the
      development of immune memory. This could pose a risk to the development of immune
      memory in persons previously infected with or vaccinated against influenza. Here,
      we explored strategies to overcome original antigenic sin responses in mice
      sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1
      (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell
      activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene
      based oil-in-water nanoemulsion (NE)], upon administration during the second
      viral exposure, completely protected mice from a lethal challenge and enhanced
      neutralizing-Ab titers against the second virus. Interestingly, PT and NE
      adjuvants when administered during the first immunization even prevented original
      antigenic sin in subsequent immunization without any adjuvants. As an alternative
      to using adjuvants, we also found that repeated immunization with the second
      viral strain relieved the effects of original antigenic sin. Taken together, our
      studies provide at least three ways of overcoming original antigenic sin.

PMID- 22869732
TI  - BRCA1 and HSP90 cooperate in homologous and non-homologous DNA double-strand
      break repair and G2/M checkpoint activation.
AB  - Expression of functional breast cancer susceptibility gene 1 (BRCA1) in human
      breast and ovarian cancers is associated with resistance to platinum-based
      chemotherapeutics and poly(ADP ribose) polymerase (PARP) inhibitors. BRCA1 is a
      nuclear tumor suppressor that is critical for resolving double-strand DNA breaks
      (DSBs) and interstrand crosslinks (ICLs) by homologous recombination (HR). In
      vitro, animal and human clinical data have demonstrated that BRCA1-deficient
      cancers are highly sensitive to ICL-inducing chemotherapeutic agents, are
      amenable to synthetic lethal approaches that exploit defects in DSB/ICL repair,
      and may be associated with improved survival. Conversely, high or restored
      expression of BRCA1 in breast and ovarian cancer is associated with therapeutic
      resistance and poor prognosis. There has been much interest in identifying agents
      that interfere with BRCA1-dependent DSB/ICL repair to restore or enhance
      sensitivity to cancer therapeutics. We demonstrate that the heat-shock protein 90
      (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin [17-AAG (Tanespimycin)],
      currently in Phase II/III clinical evaluation for several cancers, induces BRCA1
      ubiquitination and proteasomal degradation, resulting in compromised repair of
      ionizing radiation- and platinum-induced DNA damage. We show that loss of HSP90
      function abolishes BRCA1-dependent DSB repair and that BRCA1-deficient cells are
      hypersensitive to 17-AAG due to impaired Gap 2/Mitosis (G2/M) checkpoint
      activation and resultant mitotic catastrophe. In summary, we document an upstream
      HSP90-dependent regulatory point in the Fanconi anemia/BRCA DSB/ICL repair
      pathway, illuminate the role of BRCA1 in regulating damage-associated checkpoint
      and repair responses to HSP90 inhibitors, and identify BRCA1 as a clinically
      relevant target for enhancing sensitivity in refractory and/or resistant
      malignancies.

PMID- 22869733
TI  - The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in
      the filamentous bacteria Streptomyces.
AB  - In cells that exhibit apical growth, mechanisms that regulate cell polarity are
      crucial for determination of cellular shape and for the adaptation of growth to
      intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in
      eukaryotes, but less is known about polarly growing prokaryotes. An
      evolutionarily ancient form of apical growth is found in the filamentous bacteria
      Streptomyces, and is directed by a polarisome-like complex involving the
      essential protein DivIVA. We report here that this bacterial polarization
      machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which
      localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK
      regulates hyphal branching by modulating branch-site selection and some aspect of
      the underlying polarisome-splitting mechanism that controls branching of
      Streptomyces hyphae. Further, AfsK is activated by signals generated by the
      arrest of cell wall synthesis and directly communicates this to the polarisome by
      hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation
      by using a constitutively active mutant AfsK causes disassembly of apical
      polarisomes, followed by establishment of multiple hyphal branches elsewhere in
      the cell, revealing a profound impact of this kinase on growth polarity. The
      function of AfsK is reminiscent of the phoshorylation of polarity proteins and
      polarisome components by Ser/Thr protein kinases in eukaryotes.

PMID- 22869734
TI  - Oncogenic Myc translocations are independent of chromosomal location and
      orientation of the immunoglobulin heavy chain locus.
AB  - Many tumors are characterized by recurrent translocations between a tissue
      specific gene and a proto-oncogene. The juxtaposition of the Ig heavy chain gene
      and Myc in Burkitt's lymphoma and in murine plasmacytoma is a classic example.
      Regulatory elements within the heavy chain constant region locus are required for
      Myc translocation and/or deregulation. However, many genes are regulated by cis
      acting elements at distances up to 1,000 kb outside the locus. Such putative
      distal elements have not been examined for the heavy chain locus, particularly in
      the context of Myc translocations. We demonstrate that a transgene containing the
      Ig heavy chain constant region locus, inserted into five different chromosomal
      locations, can undergo translocations involving Myc. Furthermore, these
      translocations are able to generate plasmacytomas in each transgenic line. We
      conclude that the heavy chain constant region locus itself includes all of the
      elements necessary for both the translocation and the deregulation of the proto
      oncogene.

PMID- 22869735
TI  - Human superoxide dismutase 1 (hSOD1) maturation through interaction with human
      copper chaperone for SOD1 (hCCS).
AB  - Copper chaperone for superoxide dismutase 1 (SOD1), CCS, is the physiological
      partner for the complex mechanism of SOD1 maturation. We report an in vitro model
      for human CCS-dependent SOD1 maturation based on the study of the interactions of
      human SOD1 (hSOD1) with full-length WT human CCS (hCCS), as well as with hCCS
      mutants and various truncated constructs comprising one or two of the protein's
      three domains. The synergy between electrospray ionization mass spectrometry (ESI
      MS) and NMR is fully exploited. This is an in vitro study of this process at the
      molecular level. Domain 1 of hCCS is necessary to load hSOD1 with Cu(I),
      requiring the heterodimeric complex formation with hSOD1 fostered by the
      interaction with domain 2. Domain 3 is responsible for the catalytic formation of
      the hSOD1 Cys-57-Cys-146 disulfide bond, which involves both hCCS Cys-244 and Cys
      246 via disulfide transfer.

PMID- 22869736
TI  - Evolutionary trajectories explain the diversified evolution of isogamy and
      anisogamy in marine green algae.
AB  - The evolution of anisogamy (the production of gametes of different size) is the
      first step in the establishment of sexual dimorphism, and it is a fundamental
      phenomenon underlying sexual selection. It is believed that anisogamy originated
      from isogamy (production of gametes of equal size), which is considered by most
      theorists to be the ancestral condition. Although nearly all plant and animal
      species are anisogamous, extant species of marine green algae exhibit a diversity
      of mating systems including both isogamy and anisogamy. Isogamy in marine green
      algae is of two forms: isogamy with extremely small gametes and isogamy with
      larger gametes. Based on disruptive selection for fertilization success and
      zygote survival (theory of Parker, Baker, and Smith), we explored how
      environmental changes can contribute to the evolution of such complex mating
      systems by analyzing the stochastic process in the invasion simulations of
      populations of differing gamete sizes. We find that both forms of isogamy can
      evolve from other isogamous ancestors through anisogamy. The resulting
      dimensionless analysis accounts for the evolutionary stability of all types of
      mating systems in marine green algae, even in the same environment. These results
      imply that evolutionary trajectories as well as the optimality of gametes/zygotes
      played an important role in the evolution of gamete size.

PMID- 22869737
TI  - Viroid RNA redirects host DNA ligase 1 to act as an RNA ligase.
AB  - Viroids are a unique class of noncoding RNAs: composed of only a circular, single
      stranded molecule of 246-401 nt, they manage to replicate, move, circumvent host
      defenses, and frequently induce disease in higher plants. Viroids replicate
      through an RNA-to-RNA rolling-circle mechanism consisting of transcription of
      oligomeric viroid RNA intermediates, cleavage to unit-length strands, and
      circularization. Though the host RNA polymerase II (redirected to accept RNA
      templates) mediates RNA synthesis and a type-III RNase presumably cleavage of
      Potato spindle tuber viroid (PSTVd) and closely related members of the family
      Pospiviroidae, the host enzyme catalyzing the final circularization step, has
      remained elusive. In this study we propose that PSTVd subverts host DNA ligase 1,
      converting it to an RNA ligase, for the final step. To support this hypothesis,
      we show that the tomato (Solanum lycopersicum L.) DNA ligase 1 specifically and
      efficiently catalyzes circularization of the genuine PSTVd monomeric linear
      replication intermediate opened at position G95-G96 and containing 5'
      phosphomonoester and 3'-hydroxyl terminal groups. Moreover, we also show a
      decreased PSTVd accumulation and a reduced ratio of monomeric circular to total
      monomeric PSTVd forms in Nicotiana benthamiana Domin plants in which the
      endogenous DNA ligase 1 was silenced. Thus, in a remarkable example of parasitic
      strategy, viroids reprogram for their replication the template and substrate
      specificity of a DNA-dependent RNA polymerase and a DNA ligase to act as RNA
      dependent RNA polymerase and RNA ligase, respectively.

PMID- 22869738
TI  - Oligomycin frames a common drug-binding site in the ATP synthase.
AB  - We report the high-resolution (1.9 A) crystal structure of oligomycin bound to
      the subunit c(10) ring of the yeast mitochondrial ATP synthase. Oligomycin binds
      to the surface of the c(10) ring making contact with two neighboring molecules at
      a position that explains the inhibitory effect on ATP synthesis. The carboxyl
      side chain of Glu59, which is essential for proton translocation, forms an H-bond
      with oligomycin via a bridging water molecule but is otherwise shielded from the
      aqueous environment. The remaining contacts between oligomycin and subunit c are
      primarily hydrophobic. The amino acid residues that form the oligomycin-binding
      site are 100% conserved between human and yeast but are widely different from
      those in bacterial homologs, thus explaining the differential sensitivity to
      oligomycin. Prior genetics studies suggest that the oligomycin-binding site
      overlaps with the binding site of other antibiotics, including those effective
      against Mycobacterium tuberculosis, and thereby frames a common "drug-binding
      site." We anticipate that this drug-binding site will serve as an effective
      target for new antibiotics developed by rational design.

PMID- 22869739
TI  - Inducible genetic system for the axolotl.
AB  - Transgenesis promises a powerful means for assessing gene function during
      amphibian limb regeneration. This approach is complicated, however, by the need
      for embryonic appendage development to proceed unimpeded despite the genetic
      alterations one wishes to test later in the context of regeneration. Achieving
      conditional gene regulation in this amphibian has not proved to be as
      straightforward as in many other systems. In this report we describe a unique
      method for obtaining temporal control over exogenous gene expression in the
      axolotl. Based on technology derived from the Escherichia coli Lac operon,
      uninduced transgenes are kept in a repressed state by the binding of
      constitutively expressed Lac repressor protein (LacI) to operator sequences
      within the expression construct. Addition of a lactose analog, IPTG, to the
      swimming water of the axolotl is sufficient for the sugar to be taken up by
      cells, where it binds the LacI protein, thereby inducing expression of the
      repressed gene. We use this system to demonstrate an in vivo role for
      thrombospondin-4 in limb regeneration. This inducible system will allow for
      systematic analysis of phenotypes at defined developmental or regenerative time
      points. The tight regulation and robustness of gene induction combined with the
      simplicity of this strategy will prove invaluable for studying many aspects of
      axolotl biology.

PMID- 22869740
TI  - Nuclear receptor PPARgamma-regulated monoacylglycerol O-acyltransferase 1 (MGAT1)
      expression is responsible for the lipid accumulation in diet-induced hepatic
      steatosis.
AB  - Recently, hepatic peroxisome proliferator-activated receptor (PPAR)gamma has been
      implicated in hepatic lipid accumulation. We found that the C3H mouse strain does
      not express PPARgamma in the liver and, when subject to a high-fat diet, is
      resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral
      PPARgamma2 injection into B6 and C3H mice caused hepatic steatosis, and
      microarray analysis demonstrated that hepatic PPARgamma2 expression is associated
      with genes involved in fatty acid transport and the triglyceride synthesis
      pathway. In particular, hepatic PPARgamma2 expression significantly increased the
      expression of monoacylglycerol O-acyltransferase 1 (MGAT1). Promoter analysis by
      luciferase assay and electrophoretic mobility shift assay as well as chromatin
      immunoprecipitation assay revealed that PPARgamma2 directly regulates the MGAT1
      promoter activity. The MGAT1 overexpression in cultured hepatocytes enhanced
      triglyceride synthesis without an increase of PPARgamma expression. Importantly,
      knockdown of MGAT1 in the liver significantly reduced hepatic steatosis in 12-wk
      old high-fat-fed mice as well as ob/ob mice, accompanied by weight loss and
      improved glucose tolerance. These results suggest that the MGAT1 pathway induced
      by hepatic PPARgamma is critically important in the development of hepatic
      steatosis during diet-induced obesity.

PMID- 22869741
TI  - SAMBA, a plant-specific anaphase-promoting complex/cyclosome regulator is
      involved in early development and A-type cyclin stabilization.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a large multiprotein E3
      ubiquitin ligase involved in ubiquitin-dependent proteolysis of key cell cycle
      regulatory proteins, including the destruction of mitotic cyclins at the
      metaphase-to-anaphase transition. Despite its importance, the role of the APC/C
      in plant cells and the regulation of its activity during cell division remain
      poorly understood. Here, we describe the identification of a plant-specific
      negative regulator of the APC/C complex, designated SAMBA. In Arabidopsis
      thaliana, SAMBA is expressed during embryogenesis and early plant development and
      plays a key role in organ size control. Samba mutants produced larger seeds,
      leaves, and roots, which resulted from enlarged root and shoot apical meristems,
      and, additionally, they had a reduced fertility attributable to a hampered male
      gametogenesis. Inactivation of SAMBA stabilized A2-type cyclins during early
      development. Our data suggest that SAMBA regulates cell proliferation during
      early development by targeting CYCLIN A2 for APC/C-mediated proteolysis.

PMID- 22869742
TI  - Rapid divergence and expansion of the X chromosome in papaya.
AB  - X chromosomes have long been thought to conserve the structure and gene content
      of the ancestral autosome from which the sex chromosomes evolved. We compared the
      recently evolved papaya sex chromosomes with a homologous autosome of a close
      relative, the monoecious Vasconcellea monoica, to infer changes since
      recombination stopped between the papaya sex chromosomes. We sequenced 12 V.
      monoica bacterial artificial chromosomes, 11 corresponding to the papaya X
      specific region, and 1 to a papaya autosomal region. The combined V. monoica X
      orthologous sequences are much shorter (1.10 Mb) than the corresponding papaya
      region (2.56 Mb). Given that the V. monoica genome is 41% larger than that of
      papaya, this finding suggests considerable expansion of the papaya X; expansion
      is supported by a higher repetitive sequence content of the X compared with the
      papaya autosomal sequence. The alignable regions include 27 transcript-encoding
      sequences, only 6 of which are functional X/V. monoica gene pairs. Sequence
      divergence from the V. monoica orthologs is almost identical for papaya X and Y
      alleles; the Carica-Vasconcellea split therefore occurred before the papaya sex
      chromosomes stopped recombining, making V. monoica a suitable outgroup for
      inferring changes in papaya sex chromosomes. The papaya X and the hermaphrodite
      specific region of the Y(h) chromosome and V. monoica have all gained and lost
      genes, including a surprising amount of changes in the X.

PMID- 22869743
TI  - Ritual Black Drink consumption at Cahokia.
AB  - Chemical analyses of organic residues in fragments of pottery from the large site
      of Cahokia and surrounding smaller sites in Illinois reveal theobromine,
      caffeine, and ursolic acid, biomarkers for species of Ilex (holly) used to
      prepare the ritually important Black Drink. As recorded during the historic
      period, men consumed Black Drink in portions of the American Southeast for ritual
      purification. This first demonstrated discovery of biomarkers for Ilex occurs in
      beaker vessels dating between A.D. 1050 and 1250 from Cahokia, located far north
      of the known range of the holly species used to prepare Black Drink during
      historic times. The association of Ilex and beaker vessels indicates a sustained
      ritual consumption of a caffeine-laced drink made from the leaves of plants grown
      in the southern United States.

PMID- 22869744
TI  - Mass spectrometry study of a transferrin-based protein drug reveals the key role
      of protein aggregation for successful oral delivery.
AB  - A recently designed human growth hormone/transferrin fusion protein (GHT) remains
      one of the very few examples of a protein capable of eliciting measurable
      therapeutic response after oral administration. To better understand the
      underlying factors that resulted in this rare success of nonparenteral protein
      drug delivery, we analyzed proteolytic stability and receptor binding properties
      of this protein, the key factors in overcoming the primary barriers to successful
      oral delivery. Analysis of GHT by a combination of size exclusion chromatography
      and mass spectrometry revealed that a significant protein population exists in an
      oligomeric (GHTx) state in addition to the anticipated monomer (GHT1). These
      states of GHT were evaluated for their survivability in stomach-like conditions,
      as well as their ability to bind transferrin receptor (TfR). Our results reveal
      an exceptional stability of GHTx, as well as the preserved ability to bind TfR, a
      critical first step in crossing the epithelial-intestinal barrier through
      receptor-mediated transcytosis.

PMID- 22869745
TI  - Total kinetic analysis reveals how combinatorial methylation patterns are
      established on lysines 27 and 36 of histone H3.
AB  - We have developed a targeted method to quantify all combinations of methylation
      on an H3 peptide containing lysines 27 and 36 (H3K27-K36). By using stable
      isotopes that separately label the histone backbone and its methylations, we
      tracked the rates of methylation and demethylation in myeloma cells expressing
      high vs. low levels of the methyltransferase MMSET/WHSC1/NSD2. Following
      quantification of 99 labeled H3K27-K36 methylation states across time, a kinetic
      model converged to yield 44 effective rate constants qualifying each methylation
      and demethylation step as a function of the methylation state on the neighboring
      lysine. We call this approach MS-based measurement and modeling of histone
      methylation kinetics (M4K). M4K revealed that, when dimethylation states are
      reached on H3K27 or H3K36, rates of further methylation on the other site are
      reduced as much as 100-fold. Overall, cells with high MMSET have as much as 33
      fold increases in the effective rate constants for formation of H3K36 mono- and
      dimethylation. At H3K27, cells with high MMSET have elevated formation of K27me1,
      but even higher increases in the effective rate constants for its reversal by
      demethylation. These quantitative studies lay bare a bidirectional antagonism
      between H3K27 and H3K36 that controls the writing and erasing of these
      methylation marks. Additionally, the integrated kinetic model was used to
      correctly predict observed abundances of H3K27-K36 methylation states within 5%
      of that actually established in perturbed cells. Such predictive power for how
      histone methylations are established should have major value as this family of
      methyltransferases matures as drug targets.

PMID- 22869746
TI  - Spatial ordering of chromosomes enhances the fidelity of chromosome partitioning
      in cyanobacteria.
AB  - Many cyanobacteria have been shown to harbor multiple chromosome copies per cell,
      yet little is known about the organization, replication, and segregation of these
      chromosomes. Here, we visualize individual chromosomes in the cyanobacterium
      Synechococcus elongatus via time-lapse fluorescence microscopy. We find that
      chromosomes are equally spaced along the long axis of the cell and are
      interspersed with another regularly spaced subcellular compartment, the
      carboxysome. This remarkable organization of the cytoplasm along with accurate
      midcell septum placement allows for near-optimal segregation of chromosomes to
      daughter cells. Disruption of either chromosome ordering or midcell septum
      placement significantly increases the chromosome partitioning error. We find that
      chromosome replication is both asynchronous and independent of the position of
      the chromosome in the cell and that spatial organization is preserved after
      replication. Our findings on chromosome organization, replication, and
      segregation in S. elongatus provide a basis for understanding chromosome dynamics
      in bacteria with multiple chromosomes.

PMID- 22869747
TI  - Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex
      chromosome evolution.
AB  - Sex determination in papaya is controlled by a recently evolved XY chromosome
      pair, with two slightly different Y chromosomes controlling the development of
      males (Y) and hermaphrodites (Y(h)). To study the events of early sex chromosome
      evolution, we sequenced the hermaphrodite-specific region of the Y(h) chromosome
      (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule,
      and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the
      X region, mostly due to retrotransposon insertions. The papaya HSY differs from
      the X region by two large-scale inversions, the first of which likely caused the
      recombination suppression between the X and Y(h) chromosomes, followed by
      numerous additional chromosomal rearrangements. Altogether, including the X
      and/or HSY regions, 124 transcription units were annotated, including 50
      functional pairs present in both the X and HSY. Ten HSY genes had functional
      homologs elsewhere in the papaya autosomal regions, suggesting movement of genes
      onto the HSY, whereas the X region had none. Sequence divergence between 70
      transcripts shared by the X and HSY revealed two evolutionary strata in the X
      chromosome, corresponding to the two inversions on the HSY, the older of which
      evolved about 7.0 million years ago. Gene content differences between the HSY and
      X are greatest in the older stratum, whereas the gene content and order of the
      collinear regions are identical. Our findings support theoretical models of early
      sex chromosome evolution.

PMID- 22869748
TI  - Diphthamide modification on eukaryotic elongation factor 2 is needed to assure
      fidelity of mRNA translation and mouse development.
AB  - To study the role of the diphthamide modification on eukaryotic elongation factor
      2 (eEF2), we generated an eEF2 Gly(717)Arg mutant mouse, in which the first step
      of diphthamide biosynthesis is prevented. Interestingly, the Gly(717)-to-Arg
      mutation partially compensates the eEF2 functional loss resulting from
      diphthamide deficiency, possibly because the added +1 charge compensates for the
      loss of the +1 charge on diphthamide. Therefore, in contrast to mouse embryonic
      fibroblasts (MEFs) from OVCA1(-/-) mice, eEF2(G717R/G717R) MEFs retain full
      activity in polypeptide elongation and have normal growth rates. Furthermore,
      eEF2(G717R/G717R) mice showed milder phenotypes than OVCA1(-/-) mice (which are
      100% embryonic lethal) and a small fraction survived to adulthood without obvious
      abnormalities. Moreover, eEF2(G717R/G717R)/OVCA1(-/-) double mutant mice
      displayed the milder phenotypes of the eEF2(G717R/G717R) mice, suggesting that
      the embryonic lethality of OVCA1(-/-) mice is due to diphthamide deficiency. We
      confirmed that the diphthamide modification is essential for eEF2 to prevent -1
      frameshifting during translation and show that the Gly(717)-to-Arg mutation
      cannot rescue this defect.

PMID- 22869749
TI  - Role of satellite cells versus myofibers in muscle hypertrophy induced by
      inhibition of the myostatin/activin signaling pathway.
AB  - Myostatin and activin A are structurally related secreted proteins that act to
      limit skeletal muscle growth. The cellular targets for myostatin and activin A in
      muscle and the role of satellite cells in mediating muscle hypertrophy induced by
      inhibition of this signaling pathway have not been fully elucidated. Here we show
      that myostatin/activin A inhibition can cause muscle hypertrophy in mice lacking
      either syndecan4 or Pax7, both of which are important for satellite cell function
      and development. Moreover, we show that muscle hypertrophy after pharmacological
      blockade of this pathway occurs without significant satellite cell proliferation
      and fusion to myofibers and without an increase in the number of myonuclei per
      myofiber. Finally, we show that genetic ablation of Acvr2b, which encodes a high
      affinity receptor for myostatin and activin A specifically in myofibers is
      sufficient to induce muscle hypertrophy. All of these findings are consistent
      with satellite cells playing little or no role in myostatin/activin A signaling
      in vivo and render support that inhibition of this signaling pathway can be an
      effective therapeutic approach for increasing muscle growth even in disease
      settings characterized by satellite cell dysfunction.

PMID- 22869750
TI  - An accumulator model for spontaneous neural activity prior to self-initiated
      movement.
AB  - A gradual buildup of neuronal activity known as the "readiness potential"
      reliably precedes voluntary self-initiated movements, in the average time locked
      to movement onset. This buildup is presumed to reflect the final stages of
      planning and preparation for movement. Here we present a different interpretation
      of the premovement buildup. We used a leaky stochastic accumulator to model the
      neural decision of "when" to move in a task where there is no specific temporal
      cue, but only a general imperative to produce a movement after an unspecified
      delay on the order of several seconds. According to our model, when the
      imperative to produce a movement is weak, the precise moment at which the
      decision threshold is crossed leading to movement is largely determined by
      spontaneous subthreshold fluctuations in neuronal activity. Time locking to
      movement onset ensures that these fluctuations appear in the average as a gradual
      exponential-looking increase in neuronal activity. Our model accounts for the
      behavioral and electroencephalography data recorded from human subjects
      performing the task and also makes a specific prediction that we confirmed in a
      second electroencephalography experiment: Fast responses to temporally
      unpredictable interruptions should be preceded by a slow negative-going voltage
      deflection beginning well before the interruption itself, even when the subject
      was not preparing to move at that particular moment.

PMID- 22869751
TI  - Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of
      prion disease.
AB  - Copper influences the pathogenesis of prion disease, but whether it is beneficial
      or detrimental remains controversial. Copper homeostasis is also essential for
      normal physiology, as highlighted by the spectrum of diseases caused by
      disruption of the copper transporting enzymes ATP7A and ATP7B. Here, by using a
      forward genetics approach in mice, we describe the isolation of three alleles of
      Atp7a, each with different phenotypic consequences. The mildest of the three,
      Atp7a(brown), was insufficient to cause lethality in hemizygotes or mottling of
      the coat in heterozygotes, but did lead to coat hypopigmentation and reduced
      copper content in the brains of hemizygous males. When challenged with Rocky
      Mountain Laboratory scrapie, the onset of prion disease was delayed in
      Atp7a(brown) mice, and significantly less proteinase-resistant prion protein was
      found in the brains of moribund Atp7a(brown) mice compared with WT littermates.
      Our results establish that ATP7A-mediated copper homeostasis is important for the
      formation of pathogenic proteinase-resistant prion protein.

PMID- 22869752
TI  - Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and
      cognitive deficits in an Alzheimer's disease model.
AB  - In light of the rising prevalence of Alzheimer's disease (AD), new strategies to
      prevent, halt, and reverse this condition are needed urgently. Perturbations of
      brain network activity are observed in AD patients and in conditions that
      increase the risk of developing AD, suggesting that aberrant network activity
      might contribute to AD-related cognitive decline. Human amyloid precursor protein
      (hAPP) transgenic mice simulate key aspects of AD, including pathologically
      elevated levels of amyloid-beta peptides in brain, aberrant neural network
      activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral
      abnormalities. Whether these alterations are linked in a causal chain remains
      unknown. To explore whether hAPP/amyloid-beta-induced aberrant network activity
      contributes to synaptic and cognitive deficits, we treated hAPP mice with
      different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV)
      effectively reduced abnormal spike activity detected by electroencephalography.
      Chronic treatment with LEV also reversed hippocampal remodeling, behavioral
      abnormalities, synaptic dysfunction, and deficits in learning and memory in hAPP
      mice. Our findings support the hypothesis that aberrant network activity
      contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might
      also help ameliorate related abnormalities in people who have or are at risk for
      AD.

PMID- 22869753
TI  - Direct reprogramming of fibroblasts into endothelial cells capable of
      angiogenesis and reendothelialization in tissue-engineered vessels.
AB  - The generation of induced pluripotent stem (iPS) cells is an important tool for
      regenerative medicine. However, the main restriction is the risk of tumor
      development. In this study we found that during the early stages of somatic cell
      reprogramming toward a pluripotent state, specific gene expression patterns are
      altered. Therefore, we developed a method to generate partial-iPS (PiPS) cells by
      transferring four reprogramming factors (OCT4, SOX2, KLF4, and c-MYC) to human
      fibroblasts for 4 d. PiPS cells did not form tumors in vivo and clearly displayed
      the potential to differentiate into endothelial cells (ECs) in response to
      defined media and culture conditions. To clarify the mechanism of PiPS cell
      differentiation into ECs, SET translocation (myeloid leukemia-associated) (SET)
      similar protein (SETSIP) was indentified to be induced during somatic cell
      reprogramming. Importantly, when PiPS cells were treated with VEGF, SETSIP was
      translocated to the cell nucleus, directly bound to the VE-cadherin promoter,
      increasing vascular endothelial-cadherin (VE-cadherin) expression levels and EC
      differentiation. Functionally, PiPS-ECs improved neovascularization and blood
      flow recovery in a hindlimb ischemic model. Furthermore, PiPS-ECs displayed good
      attachment, stabilization, patency, and typical vascular structure when seeded on
      decellularized vessel scaffolds. These findings indicate that reprogramming of
      fibroblasts into ECs via SETSIP and VEGF has a potential clinical application.

PMID- 22869757
TI  - The Rashomon effect.

PMID- 22869756
TI  - Reprogramming IgH isotype-switched B cells to functional-grade induced
      pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) can be formed from somatic cells by a
      defined set of genetic factors; however, aberrant epigenetic silencing of the
      imprinted Dlk1-Dio3 gene cluster often hinders their developmental potency and
      ability to contribute to high-grade chimerism in mice. Here, we describe an
      approach that allows splenic B cells activated to undergo Ig heavy-chain (IgH)
      class-switch recombination (CSR) to be reprogrammed into iPSCs that contribute to
      high-grade chimerism in mice. Treatment of naive splenic B cells in culture with
      anti-CD40 plus IL-4 induces IgH CSR from IgM to IgG1 and IgE. CSR leads to
      irreversible IgH locus deletions wherein the IgM-producing CMU exons are
      permanently excised from the B-cell genome. We find that anti-CD40 plus IL-4
      activated B cells produce iPSCs that are uniformly hypermethylated in the
      imprinted Dlk1-Dio3 gene cluster and fail to produce chimerism in mice. However,
      treatment of activated B cells with the methyltransferase inhibitor 5-aza-2'
      deoxycytidine before and at early stages of reprogramming attenuates
      hypermethylation of the Dlk1-Dio3 locus in resultant iPSCs and enables them to
      form high-grade chimerism in mice. These conditions allowed us to produce
      chimeric mice in which all mature B cells were derived entirely from IgG1
      expressing B-cell-derived iPSCs. We conclude that culture conditions of activated
      B cells before and at early stages of reprogramming influence the developmental
      potency of resultant iPSCs.

PMID- 22869758
TI  - Autograft hamstring vs patellar tendon ACL reconstruction.

PMID- 22869755
TI  - Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine
      activities.
AB  - Conventional chemotherapy not only kills tumor cells but also changes gene
      expression in treatment-damaged tissues, inducing production of multiple tumor
      supporting secreted factors. This secretory phenotype was found here to be
      mediated in part by a damage-inducible cell-cycle inhibitor p21 (CDKN1A). We
      developed small-molecule compounds that inhibit damage-induced transcription
      downstream of p21. These compounds were identified as selective inhibitors of a
      transcription-regulating kinase CDK8 and its isoform CDK19. Remarkably, p21 was
      found to bind to CDK8 and stimulate its kinase activity. p21 and CDK8 also
      cooperate in the formation of internucleolar bodies, where both proteins
      accumulate. A CDK8 inhibitor suppresses damage-induced tumor-promoting paracrine
      activities of tumor cells and normal fibroblasts and reverses the increase in
      tumor engraftment and serum mitogenic activity in mice pretreated with a
      chemotherapeutic drug. The inhibitor also increases the efficacy of chemotherapy
      against xenografts formed by tumor cell/fibroblast mixtures. Microarray data
      analysis revealed striking correlations between CDK8 expression and poor survival
      in breast and ovarian cancers. CDK8 inhibition offers a promising approach to
      increasing the efficacy of cancer chemotherapy.

PMID- 22869761
TI  - Encephalitis: help from guidelines.

PMID- 22869759
TI  - Why do patients discontinue fertility treatment? A systematic review of reasons
      and predictors of discontinuation in fertility treatment.
AB  - BACKGROUND Chances of achieving parenthood are high for couples who undergo
      fertility treatment. However, many choose to discontinue before conceiving. A
      systematic review was conducted to investigate patients' stated reasons for and
      predictors of discontinuation at five fertility treatment stages.  METHODS Six
      databases were systematically searched. Search-terms referred to fertility
      treatment and discontinuation. Studies reporting on patients' stated reasons for
      or predictors of treatment discontinuation were included. A list of all reasons
      for discontinuation presented in each study was made, different categories of
      reasons were defined and the percentage of selections of each category was
      calculated. For each predictor, it was noted how many studies investigated it and
      how many found a positive and/or negative association with discontinuation.   
      RESULTS The review included 22 studies that sampled 21 453 patients from eight
      countries. The most selected reasons for discontinuation were: postponement of
      treatment (39.18%, postponement of treatment or unknown 19.17%), physical and
      psychological burden (19.07%, psychological burden 14%, physical burden 6.32%),
      relational and personal problems (16.67%, personal reasons 9.27%, relational
      problems 8.83%), treatment rejection (13.23%) and organizational (11.68%) and
      clinic (7.71%) problems. Some reasons were common across stages (e.g.
      psychological burden). Others were stage-specific (e.g. treatment rejection
      during workup). None of the predictors reported were consistently associated with
      discontinuation.  CONCLUSIONS Much longitudinal and theory led research is
      required to explain discontinuation. Meanwhile, treatment burden should be
      addressed by better care organization and support for patients. Patients should
      be well informed, have the opportunity to discuss values and worries about
      treatment and receive advice to decide about continuing treatment.

PMID- 22869754
TI  - Resolution of ray-finned fish phylogeny and timing of diversification.
AB  - Ray-finned fishes make up half of all living vertebrate species. Nearly all ray
      finned fishes are teleosts, which include most commercially important fish
      species, several model organisms for genomics and developmental biology, and the
      dominant component of marine and freshwater vertebrate faunas. Despite the
      economic and scientific importance of ray-finned fishes, the lack of a single
      comprehensive phylogeny with corresponding divergence-time estimates has limited
      our understanding of the evolution and diversification of this radiation. Our
      analyses, which use multiple nuclear gene sequences in conjunction with 36 fossil
      age constraints, result in a well-supported phylogeny of all major ray-finned
      fish lineages and molecular age estimates that are generally consistent with the
      fossil record. This phylogeny informs three long-standing problems: specifically
      identifying elopomorphs (eels and tarpons) as the sister lineage of all other
      teleosts, providing a unique hypothesis on the radiation of early euteleosts, and
      offering a promising strategy for resolution of the "bush at the top of the tree"
      that includes percomorphs and other spiny-finned teleosts. Contrasting our
      divergence time estimates with studies using a single nuclear gene or whole
      mitochondrial genomes, we find that the former underestimates ages of the oldest
      ray-finned fish divergences, but the latter dramatically overestimates ages for
      derived teleost lineages. Our time-calibrated phylogeny reveals that much of the
      diversification leading to extant groups of teleosts occurred between the late
      Mesozoic and early Cenozoic, identifying this period as the "Second Age of
      Fishes."

PMID- 22869762
TI  - A practical guide to the treatment of neuromyelitis optica.

PMID- 22869763
TI  - Myoclonus: a pragmatic approach.
AB  - Myoclonus is a brief (less than half a second)contraction involving agonist and
      antagonist muscles, leading to a sudden jerk. It may be a normal phenomenon,as in
      the so-called 'sleep starts'. When pathological, myoclonus is a symptom of a
      broad range of neurological and systemic diseases. Alternatively, it may signal
      non-organic illness (8% of myoclonus is psychogenic). This review provides
      pragmatic and systematic guidance to the assessment and differential diagnosis of
      adult patients presenting with myoclonus.

PMID- 22869764
TI  - Normal anatomy of the brain on CT and MRI with a few normal variants.

PMID- 22869765
TI  - Successful outcome of Epstein-Barr virus encephalitis managed with bilateral
      craniectomy, corticosteroids and aciclovir.
AB  - We present a 19-year-old woman with severe encephalitis and raised intracranial
      pressure requiring decompressive craniectomy. Her clinical features were
      consistent with encephalitis in the context of acute primary Epstein-Barr virus
      (EBV) infection (infectious mononucleosis). Serology, bone marrow aspirate and
      PCR of blood and cerebrospinal fluid confirmed the diagnosis. She was treated
      with corticosteroids and aciclovir. She was critically unwell for 3 weeks,
      requiring artificial ventilation but eventually made a good recovery. EBV
      encephalitis is uncommon, making the diagnosis and decisions about clinical
      management challenging.

PMID- 22869766
TI  - Acute cerebellar ataxia due to Epstein-Barr virus.

PMID- 22869767
TI  - How to do it: how to get the most out of cerebrospinal fluid cytology.

PMID- 22869768
TI  - Lesley's story: a case report, and discussion of challenges faced in end-of-life
      care for progressive neurological disease.

PMID- 22869769
TI  - Letter from the Antipodes.

PMID- 22869770
TI  - Recurrent sensory and motor neuropathy.

PMID- 22869771
TI  - Widespread intracerebral metastases from prostate adenocarcinoma.

PMID- 22869772
TI  - Medicine 0--alternative medicine 1.

PMID- 22869773
TI  - Medicine 2, alternative medicine 1: a commentary on Dr Stern's paper.

PMID- 22869774
TI  - Susac's syndrome.

PMID- 22869775
TI  - Commentary on Susac article.

PMID- 22869776
TI  - Blood films in the investigation of chorea.

PMID- 22869777
TI  - The optic papilla ('inny' or 'outy') and the origins of papilloedema.

PMID- 22869778
TI  - We MUST not call it MUS.

PMID- 22869780
TI  - Loss of Bmyc results in increased apoptosis associated with upregulation of Myc
      expression in juvenile murine testis.
AB  - Bmyc is a member of the Myc family of transcriptional regulators in the mouse and
      the rat. It is predominantly expressed in hormonally controlled tissues, with
      highest level of expression in the epididymis. The BMYC protein has been shown to
      function as a transcription factor in vitro and to inhibit MYC. To study the
      significance of BMYC in vivo, a Bmyc knockout (KO) mouse model was generated by
      homologous recombination. The KO mice were viable and fertile and did not display
      gross morphological or histological changes compared to the WT mice. However, the
      testes and the epididymides of the KO mice were smaller than those of the WT
      mice. Correspondingly, a tendency for a lower sperm concentration in the cauda
      epididymides of the KO mice was detected. The testosterone produced/testis was
      significantly reduced, and accordingly, the LH levels were increased in the KO
      mice. Also, the expression levels of Myc and several of its target genes were
      elevated in the testes of prepubertal KO mice, whereas no differences in gene
      expression levels were detected in adult mice. Associated with the increased Myc
      expression, more apoptotic spermatogenic cells were detected in the seminiferous
      tubules of the KO mice. In conclusion, our data suggest that Bmyc is a regulator
      of Myc in vivo and that overexpression of Myc in the developing testis leads to
      increased apoptosis of spermatogenic cells.

PMID- 22869781
TI  - Spermatid development in XO male mice with varying Y chromosome short-arm gene
      content: evidence for a Y gene controlling the initiation of sperm morphogenesis.
AB  - We recently used three XO male mouse models with varying Y short-arm (Yp) gene
      complements, analysed at 30 days post partum, to demonstrate a Yp gene
      requirement for the apoptotic elimination of spermatocytes with a univalent X
      chromosome at the first meiotic metaphase. The three mouse models were i)
      XSxr(a)O in which the Yp-derived Tp(Y)1Ct(Sxr-a) sex reversal factor provides an
      almost complete Yp gene complement, ii) XSxr(b)O,Eif2s3y males in which
      Tp(Y)1Ct(Sxr-b) has a deletion completely or partially removing eight Yp genes -
      the Yp gene Eif2s3y has been added as a transgene to support spermatogonial
      proliferation, and iii) XOSry,Eif2s3y males in which the Sry transgene directs
      gonad development along the male pathway. In this study, we have used the same
      mouse models analysed at 6 weeks of age to investigate potential Yp gene
      involvement in spermiogenesis. We found that all three mouse models produce
      haploid and diploid spermatids and that the diploid spermatids showed frequent
      duplication of the developing acrosomal cap during the early stages. However,
      only in XSxr(a)O males did spermiogenesis continue to completion. Most
      strikingly, in XOSry,Eif2s3y males, spermatid development arrested at round
      spermatid step 7 so that no sperm head restructuring or tail development was
      observed. In contrast, in XSxr(b)O,Eif2s3y males, spermatids with substantial
      sperm head and tail morphogenesis could be easily found, although this was
      delayed compared with XSxr(a)O. We conclude that Sxr(a) (and therefore Yp)
      includes genetic information essential for sperm morphogenesis and that this is
      partially retained in Sxr(b).

PMID- 22869786
TI  - Occupational exposure to body fluids among health care workers in Georgia.
AB  - BACKGROUND: Health care workers (HCWs) are at increased risk of being infected
      with blood-borne pathogens. AIMS: To evaluate risk of occupational exposure to
      blood-borne viruses and determine the prevalence of human immunodeficiency virus
      (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among HCWs in Georgia.
      METHODS: The sample included HCWs from seven medical institutions in five cities
      in Georgia. A self-administered questionnaire was used to collect information on
      demographic, occupational and personal risk factors for blood-borne viruses.
      After obtaining informed consent, blood was drawn from the study participants for
      a seroprevalence study of HBV, HCV and HIV infections. RESULTS: There were 1386
      participating HCWs from a number of departments, including surgery (29%),
      internal medicine (19%) and intensive care (19%). Nosocomial risk events were
      reported by the majority of HCWs, including accidental needlestick injury (45%),
      cuts with contaminated instruments (38%) and blood splashes (46%). The most
      frequent risk for receiving a cut was related to a false move during a procedure,
      reassembling devices and handing devices to a colleague. The highest proportion
      of needlestick injuries among physicians (22%) and nurses (39%) was related to
      recapping of used needles. No HIV-infected HCW was identified. Prevalence of HCV
      infection was 5%, anti-HBc was present among 29% with 2% being HBsAg carriers.
      CONCLUSIONS: Data from this study can be utilized in educational programs and
      implementation of universal safety precautions for HCWs in Georgia to help
      achieve similar reductions in blood-borne infection transmission to those
      achieved in developed countries.

PMID- 22869787
TI  - Good news, good news: occupational and household activities are important for
      energy expenditure, but sport and recreation remain the best buy for public
      health.

PMID- 22869788
TI  - NCD prevention: investments [corrected] that work for physical activity.

PMID- 22869789
TI  - Plyometric training programmes improve motor performance in prepubertal children.

PMID- 22869790
TI  - The evolving contribution of hematopoietic progenitor cells to lymphomagenesis.
AB  - Recent genomic studies have outlined a landscape of recurrent alterations within
      some subtypes of lymphoid cancer. Yet, the timing and cellular contexts during
      which these alterations occur (ie, the molecular ontogeny) remain poorly
      understood. Lymphoid malignancies offer an exceptional opportunity to delineate
      the ontogeny of somatic alterations, as lymphocyte differentiation absolutely
      requires the introduction of indelible genetic rearrangements at antigen receptor
      loci during specific stages of maturation. We review competing models of
      lymphomagenesis and highlight evolving evidence that somatic alterations in
      uncommitted hematopoietic progenitors contribute to some mature lymphoid
      neoplasms. These progenitors could serve as reservoirs for further clonal
      evolution and thereby contribute to therapeutic resistance, tumor relapse, and
      the development of second hematologic malignancies. Defining the pathways that
      are dysregulated within early progenitors and the ontogeny of subsequent
      alterations that contribute to lymphoid transformation could establish novel
      therapeutic targets across a variety of hematologic malignancies and even guide
      avenues for future preventive strategies.

PMID- 22869791
TI  - Systematic analysis of microRNA fingerprints in thrombocythemic platelets using
      integrated platforms.
AB  - Posttranscriptional and translational controls mediated by microRNAs (miRNA)
      regulate diverse biologic processes. We dissected regulatory effects of miRNAs
      relevant to megakaryocytopoiesis and platelet biology by analyzing expression
      patterns in 79 subjects with thrombocytosis and controls, and integrated data
      with transcriptomic and proteomic platforms. We validated a unique 21-miRNA
      genetic fingerprint associated with thrombocytosis, and demonstrated that a 3
      member subset defines essential thrombocythemia (ET). The genetic signature
      includes functional guide and passenger strands of the previously uncharacterized
      miR 490 (5p and 3p), which displayed restricted, low-level expression in
      megakaryocytes/platelets (compared with leukocytes), and aberrant expression
      during thrombocytosis, most profound in ET. Overexpression of miR 490 in a
      bilineage differentiation model of megakaryocyte/erythroid progenitor formation
      was insufficient for hematopoietic colony differentiation and/or lineage
      specification. Integration of transcriptomic and mass spectrometric datasets with
      functional reporter assays identified dishevelled associated activator of
      morphogenesis 1 (DAAM1) as a miR 490 5p protein target demonstrating decreased
      expression in ET platelets, putatively by translational control (and not by mRNA
      target degradation). Our data define a dysregulated miRNA fingerprint in
      thrombocytosis and support a developmentally restricted function of miR 490 (and
      its putative DAAM1 target) to conditions associated with exaggerated
      megakaryocytopoiesis and/or proplatelet formation.

PMID- 22869792
TI  - Dicer is selectively important for the earliest stages of erythroid development.
AB  - MicroRNAs (miRs) are involved in many aspects of normal and malignant
      hematopoiesis, including hematopoietic stem cell (HSC) self-renewal,
      proliferation, and terminal differentiation. However, a role for miRs in the
      generation of the earliest stages of lineage committed progenitors from HSCs has
      not been identified. Using Dicer inactivation, we show that the miR complex is
      not only essential for HSC maintenance but is specifically required for their
      erythroid programming and subsequent generation of committed erythroid
      progenitors. In bipotent pre-MegEs, loss of Dicer up-regulated transcription
      factors preferentially expressed in megakaryocyte progenitors (Gata2 and Zfpm1)
      and decreased expression of the erythroid-specific Klf1 transcription factor.
      These results show a specific requirement for Dicer in acquisition of erythroid
      lineage programming and potential in HSCs and their subsequent erythroid lineage
      differentiation, and in particular indicate a role for the miR complex in
      achieving proper balance of lineage-specific transcriptional regulators necessary
      for HSC multilineage potential to be maintained.

PMID- 22869793
TI  - The first comprehensive and quantitative analysis of human platelet protein
      composition allows the comparative analysis of structural and functional
      pathways.
AB  - Antiplatelet treatment is of fundamental importance in combatting
      functions/dysfunction of platelets in the pathogenesis of cardiovascular and
      inflammatory diseases. Dysfunction of anucleate platelets is likely to be
      completely attributable to alterations in posttranslational modifications and
      protein expression. We therefore examined the proteome of platelets highly
      purified from fresh blood donations, using elaborate protocols to ensure
      negligible contamination by leukocytes, erythrocytes, and plasma. Using
      quantitative mass spectrometry, we created the first comprehensive and
      quantitative human platelet proteome, comprising almost 4000 unique proteins,
      estimated copy numbers for ~ 3700 of those, and assessed intersubject (4 donors)
      as well as intrasubject (3 different blood samples from 1 donor) variations of
      the proteome. For the first time, our data allow for a systematic and weighted
      appraisal of protein networks and pathways in human platelets, and indicate the
      feasibility of differential and comprehensive proteome analyses from small blood
      donations. Because 85% of the platelet proteome shows no variation between
      healthy donors, this study represents the starting point for disease-oriented
      platelet proteomics. In the near future, comprehensive and quantitative
      comparisons between normal and well-defined dysfunctional platelets, or between
      platelets obtained from donors at various stages of chronic cardiovascular and
      inflammatory diseases will be feasible.

PMID- 22869794
TI  - Geoengineering: taking control of our planet's climate?

PMID- 22869795
TI  - Geoengineering the climate: an overview and update.
AB  - The climate change that we are experiencing now is caused by an increase in
      greenhouse gases due to human activities, including burning fossil fuels,
      agriculture and deforestation. There is now widespread belief that a global
      warming of greater than 2( degrees )C above pre-industrial levels would be
      dangerous and should therefore be avoided. However, despite growing concerns over
      climate change and numerous international attempts to agree on reductions of
      global CO(2) emissions, these have continued to climb. This has led some
      commentators to suggest more radical 'geoengineering' alternatives to
      conventional mitigation by reductions in CO(2) emissions. Geoengineering is
      deliberate intervention in the climate system to counteract man-made global
      warming. There are two main classes of geoengineering: direct carbon dioxide
      removal and solar radiation management that aims to cool the planet by reflecting
      more sunlight back to space. The findings of the review of geoengineering carried
      out by the UK Royal Society in 2009 are summarized here, including the climate
      effects, costs, risks and research and governance needs for various approaches.
      The possible role of geoengineering in a portfolio of responses to climate change
      is discussed, and various recent initiatives to establish good governance of
      research activity are reviewed. Key findings include the following.-
      Geoengineering is not a magic bullet and not an alternative to emissions
      reductions.  - Cutting global greenhouse gas emissions must remain our highest
      priority. (i) But this is proving to be difficult, and geoengineering may be
      useful to support it.  - Geoengineering is very likely to be technically
      possible. (i) However, there are major uncertainties and potential risks
      concerning effectiveness, costs and social and environmental impacts.  - Much
      more research is needed, as well as public engagement and a system of regulation
      (for both deployment and for possible large-scale field tests).  - The
      acceptability of geoengineering will be determined as much by social, legal and
      political issues as by scientific and technical factors. Some methods of both
      types would involve release of materials to the environment, either to the
      atmosphere or to the oceans, in areas beyond national jurisdiction. The intended
      impacts on climate would in any case affect many or all countries, possibly to a
      variable extent. There are therefore inherent international implications for
      deployment of such geoengineering methods (and possibly also for some forms of
      research), which need early and collaborative consideration, before any
      deployment or large-scale experiments could be undertaken responsibly.

PMID- 22869796
TI  - Exploring early public responses to geoengineering.
AB  - Proposals for geoengineering the Earth's climate are prime examples of emerging
      or 'upstream' technologies, because many aspects of their effectiveness, cost and
      risks are yet to be researched, and in many cases are highly uncertain. This
      paper contributes to the emerging debate about the social acceptability of
      geoengineering technologies by presenting preliminary evidence on public
      responses to geoengineering from two of the very first UK studies of public
      perceptions and responses. The discussion draws upon two datasets: qualitative
      data (from an interview study conducted in 42 households in 2009), and
      quantitative data (from a subsequent nationwide survey (n=1822) of British public
      opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low
      in both cases. The data from the survey indicate that, when briefly explained to
      people, carbon dioxide removal approaches were preferred to solar radiation
      management, while significant positive correlations were also found between
      concern about climate change and support for different geoengineering approaches.
      We discuss some of the wider considerations that are likely to shape public
      perceptions of geoengineering as it enters the media and public sphere, and
      conclude that, aside from technical considerations, public perceptions are likely
      to prove a key element influencing the debate over questions of the acceptability
      of geoengineering proposals.

PMID- 22869797
TI  - The runaway greenhouse: implications for future climate change, geoengineering
      and planetary atmospheres.
AB  - The ultimate climate emergency is a 'runaway greenhouse': a hot and water-vapour
      rich atmosphere limits the emission of thermal radiation to space, causing
      runaway warming. Warming ceases only after the surface reaches approximately 1400
      K and emits radiation in the near-infrared, where water is not a good greenhouse
      gas. This would evaporate the entire ocean and exterminate all planetary life.
      Venus experienced a runaway greenhouse in the past, and we expect that the Earth
      will in around 2 billion years as solar luminosity increases. But could we bring
      on such a catastrophe prematurely, by our current climate-altering activities?
      Here, we review what is known about the runaway greenhouse to answer this
      question, describing the various limits on outgoing radiation and how climate
      will evolve between these. The good news is that almost all lines of evidence
      lead us to believe that is unlikely to be possible, even in principle, to trigger
      full a runaway greenhouse by addition of non-condensible greenhouse gases such as
      carbon dioxide to the atmosphere. However, our understanding of the dynamics,
      thermodynamics, radiative transfer and cloud physics of hot and steamy
      atmospheres is weak. We cannot therefore completely rule out the possibility that
      human actions might cause a transition, if not to full runaway, then at least to
      a much warmer climate state than the present one. High climate sensitivity might
      provide a warning. If we, or more likely our remote descendants, are threatened
      with a runaway greenhouse, then geoengineering to reflect sunlight might be
      life's only hope. Injecting reflective aerosols into the stratosphere would be
      too short-lived, and even sunshades in space might require excessive maintenance.
      In the distant future, modifying Earth's orbit might provide a sustainable
      solution. The runaway greenhouse also remains relevant in planetary sciences and
      astrobiology: as extrasolar planets smaller and nearer to their stars are
      detected, some will be in a runaway greenhouse state.

PMID- 22869798
TI  - Marine cloud brightening.
AB  - The idea behind the marine cloud-brightening (MCB) geoengineering technique is
      that seeding marine stratocumulus clouds with copious quantities of roughly
      monodisperse sub-micrometre sea water particles might significantly enhance the
      cloud droplet number concentration, and thereby the cloud albedo and possibly
      longevity. This would produce a cooling, which general circulation model (GCM)
      computations suggest could-subject to satisfactory resolution of technical and
      scientific problems identified herein-have the capacity to balance global warming
      up to the carbon dioxide-doubling point. We describe herein an account of our
      recent research on a number of critical issues associated with MCB. This involves
      (i) GCM studies, which are our primary tools for evaluating globally the
      effectiveness of MCB, and assessing its climate impacts on rainfall amounts and
      distribution, and also polar sea-ice cover and thickness; (ii) high-resolution
      modelling of the effects of seeding on marine stratocumulus, which are required
      to understand the complex array of interacting processes involved in cloud
      brightening; (iii) microphysical modelling sensitivity studies, examining the
      influence of seeding amount, seed-particle salt-mass, air-mass characteristics,
      updraught speed and other parameters on cloud-albedo change; (iv) sea water spray
      production techniques; (v) computational fluid dynamics studies of possible large
      scale periodicities in Flettner rotors; and (vi) the planning of a three-stage
      limited-area field research experiment, with the primary objectives of technology
      testing and determining to what extent, if any, cloud albedo might be enhanced by
      seeding marine stratocumulus clouds on a spatial scale of around 100*100 km. We
      stress that there would be no justification for deployment of MCB unless it was
      clearly established that no significant adverse consequences would result. There
      would also need to be an international agreement firmly in favour of such action.

PMID- 22869799
TI  - Lifting options for stratospheric aerosol geoengineering: advantages of tethered
      balloon systems.
AB  - The Royal Society report 'Geoengineering the Climate' identified solar radiation
      management using albedo-enhancing aerosols injected into the stratosphere as the
      most affordable and effective option for geoengineering, but did not consider in
      any detail the options for delivery. This paper provides outline engineering
      analyses of the options, both for batch-delivery processes, following up on
      previous work for artillery shells, missiles, aircraft and free-flying balloons,
      as well as a more lengthy analysis of continuous-delivery systems that require a
      pipe connected to the ground and supported at a height of 20 km, either by a
      tower or by a tethered balloon. Towers are shown not to be practical, but a
      tethered balloon delivery system, with high-pressure pumping, appears to have
      much lower operating and capital costs than all other delivery options. Instead
      of transporting sulphuric acid mist precursors, such a system could also be used
      to transport slurries of high refractive index particles such as coated titanium
      dioxide. The use of such particles would allow useful experiments on opacity,
      coagulation and atmospheric chemistry at modest rates so as not to perturb
      regional or global climatic conditions, thus reducing scale-up risks. Criteria
      for particle choice are discussed, including the need to minimize or prevent
      ozone destruction. The paper estimates the time scales and relatively modest
      costs required if a tethered balloon system were to be introduced in a measured
      way with testing and development work proceeding over three decades, rather than
      in an emergency. The manufacture of a tether capable of sustaining the high
      tensions and internal pressures needed, as well as strong winds, is a significant
      challenge, as is the development of the necessary pumping and dispersion
      technologies. The greatest challenge may be the manufacture and launch of very
      large balloons, but means have been identified to significantly reduce the size
      of such balloons or aerostats.

PMID- 22869800
TI  - Regional climate change mitigation with crops: context and assessment.
AB  - The intention of this review is to place crop albedo biogeoengineering in the
      wider picture of climate manipulation. Crop biogeoengineering is considered
      within the context of the long-term modification of the land surface for
      agriculture over several thousand years. Biogeoengineering is also critiqued in
      relation to other geoengineering schemes in terms of mitigation power and
      adherence to social principles for geoengineering. Although its impact is small
      and regional, crop biogeoengineering could be a useful and inexpensive component
      of an ensemble of geoengineering schemes to provide temperature mitigation. The
      method should not detrimentally affect food security and there may even be
      positive impacts on crop productivity, although more laboratory and field
      research is required in this area to understand the underlying mechanisms.

PMID- 22869801
TI  - Ocean acidification in a geoengineering context.
AB  - Fundamental changes to marine chemistry are occurring because of increasing
      carbon dioxide (CO(2)) in the atmosphere. Ocean acidity (H(+) concentration) and
      bicarbonate ion concentrations are increasing, whereas carbonate ion
      concentrations are decreasing. There has already been an average pH decrease of
      0.1 in the upper ocean, and continued unconstrained carbon emissions would
      further reduce average upper ocean pH by approximately 0.3 by 2100. Laboratory
      experiments, observations and projections indicate that such ocean acidification
      may have ecological and biogeochemical impacts that last for many thousands of
      years. The future magnitude of such effects will be very closely linked to
      atmospheric CO(2); they will, therefore, depend on the success of emission
      reduction, and could also be constrained by geoengineering based on most carbon
      dioxide removal (CDR) techniques. However, some ocean-based CDR approaches would
      (if deployed on a climatically significant scale) re-locate acidification from
      the upper ocean to the seafloor or elsewhere in the ocean interior. If solar
      radiation management were to be the main policy response to counteract global
      warming, ocean acidification would continue to be driven by increases in
      atmospheric CO(2), although with additional temperature-related effects on CO(2)
      and CaCO(3) solubility and terrestrial carbon sequestration.

PMID- 22869802
TI  - Interactions between reducing CO2 emissions, CO2 removal and solar radiation
      management.
AB  - We use a simple carbon cycle-climate model to investigate the interactions
      between a selection of idealized scenarios of mitigated carbon dioxide emissions,
      carbon dioxide removal (CDR) and solar radiation management (SRM). Two CO(2)
      emissions trajectories differ by a 15-year delay in the start of mitigation
      activity. SRM is modelled as a reduction in incoming solar radiation that fully
      compensates the radiative forcing due to changes in atmospheric CO(2)
      concentration. Two CDR scenarios remove 300 PgC by afforestation (added to
      vegetation and soil) or 1000 PgC by bioenergy with carbon capture and storage
      (removed from system). Our results show that delaying the start of mitigation
      activity could be very costly in terms of the CDR activity needed later to limit
      atmospheric CO(2) concentration (and corresponding global warming) to a given
      level. Avoiding a 15-year delay in the start of mitigation activity is more
      effective at reducing atmospheric CO(2) concentrations than all but the maximum
      type of CDR interventions. The effects of applying SRM and CDR together are
      additive, and this shows most clearly for atmospheric CO(2) concentration. SRM
      causes a significant reduction in atmospheric CO(2) concentration due to
      increased carbon storage by the terrestrial biosphere, especially soils. However,
      SRM has to be maintained for many centuries to avoid rapid increases in
      temperature and corresponding increases in atmospheric CO(2) concentration due to
      loss of carbon from the land.

PMID- 22869803
TI  - Cumulative carbon as a policy framework for achieving climate stabilization.
AB  - The primary objective of the United Nations Framework Convention on Climate
      Change is to stabilize greenhouse gas concentrations at a level that will avoid
      dangerous climate impacts. However, greenhouse gas concentration stabilization is
      an awkward framework within which to assess dangerous climate change on account
      of the significant lag between a given concentration level and the eventual
      equilibrium temperature change. By contrast, recent research has shown that
      global temperature change can be well described by a given cumulative carbon
      emissions budget. Here, we propose that cumulative carbon emissions represent an
      alternative framework that is applicable both as a tool for climate mitigation as
      well as for the assessment of potential climate impacts. We show first that both
      atmospheric CO(2) concentration at a given year and the associated temperature
      change are generally associated with a unique cumulative carbon emissions budget
      that is largely independent of the emissions scenario. The rate of global
      temperature change can therefore be related to first order to the rate of
      increase of cumulative carbon emissions. However, transient warming over the next
      century will also be strongly affected by emissions of shorter lived forcing
      agents such as aerosols and methane. Non-CO(2) emissions therefore contribute to
      uncertainty in the cumulative carbon budget associated with near-term temperature
      targets, and may suggest the need for a mitigation approach that considers
      separately short- and long-lived gas emissions. By contrast, long-term
      temperature change remains primarily associated with total cumulative carbon
      emissions owing to the much longer atmospheric residence time of CO(2) relative
      to other major climate forcing agents.

PMID- 22869804
TI  - An air-liquid contactor for large-scale capture of CO2 from air.
AB  - We present a conceptually simple method for optimizing the design of a gas-liquid
      contactor for capture of carbon dioxide from ambient air, or 'air capture'. We
      apply the method to a slab geometry contactor that uses components, design and
      fabrication methods derived from cooling towers. We use mass transfer data
      appropriate for capture using a strong NaOH solution, combined with engineering
      and cost data derived from engineering studies performed by Carbon Engineering
      Ltd, and find that the total costs for air contacting alone-no regeneration-can
      be of the order of $60 per tonne CO(2). We analyse the reasons why our cost
      estimate diverges from that of other recent reports and conclude that the
      divergence arises from fundamental design choices rather than from differences in
      costing methodology. Finally, we review the technology risks and conclude that
      they can be readily addressed by prototype testing.

PMID- 22869805
TI  - Peatland geoengineering: an alternative approach to terrestrial carbon
      sequestration.
AB  - Terrestrial and oceanic ecosystems contribute almost equally to the sequestration
      of ca 50 per cent of anthropogenic CO(2) emissions, and already play a role in
      minimizing our impact on Earth's climate. On land, the majority of the
      sequestered carbon enters soil carbon stores. Almost one-third of that soil
      carbon can be found in peatlands, an area covering just 2-3% of the Earth's
      landmass. Peatlands are thus well established as powerful agents of carbon
      capture and storage; the preservation of archaeological artefacts, such as
      ancient bog bodies, further attest to their exceptional preservative properties.
      Peatlands have higher carbon storage densities per unit ecosystem area than
      either the oceans or dry terrestrial systems. However, despite attempts over a
      number of years at enhancing carbon capture in the oceans or in land-based
      afforestation schemes, no attempt has yet been made to optimize peatland carbon
      storage capacity or even to harness peatlands to store externally captured
      carbon. Recent studies suggest that peatland carbon sequestration is due to the
      inhibitory effects of phenolic compounds that create an 'enzymic latch' on
      decomposition. Here, we propose to harness that mechanism in a series of peatland
      geoengineering strategies whereby molecular, biogeochemical, agronomical and
      afforestation approaches increase carbon capture and long-term sequestration in
      peat-forming terrestrial ecosystems.

PMID- 22869806
TI  - A 29-year-old immigrant with chronic diarrhea.

PMID- 22869817
TI  - Biological microdosimetry based on radiation cytotoxicity data.
AB  - Researchers in the field of radiation microdosimetry have attempted to explain
      the relative biological effectiveness (RBE) of different ionising photon
      radiation sources on the basis of the singly stochastic, microdose metric lineal
      energy y, which only addresses physical stochasticity related to energy (epsilon)
      deposition via single events in the critical targets (cell nuclei assumed here).
      Biological stochasticity related to variable nuclei geometries and cell
      orientations (relative to the incoming radiation) is usually not addressed. Here
      a doubly stochastic microdose metric, the single-event hit size q (=epsilon/T),
      is introduced which allows the track length T to be stochastic. The new metric is
      used in a plausible model of metabolic-activity-based in vitro cytotoxicity of
      low-dose ionising photon radiation. The cytotoxicity model has parameters E{q}
      (average single-event hit size with q assumed to be exponentially distributed)
      and E{alpha}, which is the average value of the cellular response parameter
      alpha. E{alpha} is referred to as the biological signature and it is independent
      of q. Only E{q} is needed for determination of RBE. The model is used to obtain
      biological-microdosimetry-based q spectra for 320-kV X-rays and (137)Cs gamma
      rays and the related RBE for cytotoxicity. The spectra are similar to published
      lineal energy y spectra for 200-kV X-rays and (60)Co gamma rays for 1-MUm
      biological targets.

PMID- 22869818
TI  - Interlaboratory comparison of dicentric chromosome assay using electronically
      transmitted images.
AB  - The bottleneck in data acquisition during biological dosimetry based on a
      dicentric assay is the need to score dicentrics in a large number of lymphocytes.
      One way to increase the capacity of a given laboratory is to use the ability of
      skilled operators from other laboratories. This can be done using image analysis
      systems and distributing images all around the world. Two exercises were
      conducted to test the efficiency of such an approach involving 10 laboratories.
      During the first exercise (E1), the participant laboratories analysed the same
      images derived from cells exposed to 0.5 and 3 Gy; 100 images were sent to all
      participants for both doses. Whatever the dose, only about half of the cells were
      complete with well-spread metaphases suitable for analysis. A coefficient of
      variation (CV) on the standard deviation of ~15 % was obtained for both doses.
      The trueness was better for 3 Gy (0.6 %) than for 0.5 Gy (37.8 %). The number of
      estimated doses classified as satisfactory according to the z-score was 3 at 0.5
      Gy and 8 at 3 Gy for 10 dose estimations. In the second exercise, an emergency
      situation was tested, each laboratory was required to score a different set of 50
      images in 2 d extracted from 500 downloaded images derived from cells exposed to
      0.5 Gy. Then the remaining 450 images had to be scored within a week. Using 50
      different images, the CV on the estimated doses (79.2 %) was not as good as in
      E1, probably associated to a lower number of cells analysed (50 vs. 100) or from
      the fact that laboratories analysed a different set of images. The trueness for
      the dose was better after scoring 500 cells (22.5 %) than after 50 cells (26.8
      %). For the 10 dose estimations, the number of doses classified as satisfactory
      according to the z-score was 9, for both 50 and 500 cells. Overall, the results
      obtained support the feasibility of networking using electronically transmitted
      images. However, before its implementation some issues should be elucidated, such
      as the number and resolution of the images to be sent, and the harmonisation of
      the scoring criteria. Additionally, a global website able to be used for the
      different regional networks, like Share Points, will be desirable to facilitate
      worldwide communication.

PMID- 22869819
TI  - Potential of natural gamma-ray spectrometry for mapping and environmental
      monitoring of black-sand beach deposits on the northern coast of Sinai, Egypt.
AB  - The concentrations and distributions of naturally occurring radioactive materials
      were studied with the aim of detecting and mapping radioactive anomalies as well
      as monitoring the environment for black-sand beach deposits in Northern Sinai,
      Egypt. For this purpose, ground gamma-ray spectrometric surveys were conducted
      using a portable GS-512 spectrometer, with an NaI (Tl) detector, on an area 77.5
      km(2) in surface area located between the cities of Rafah and Elareish on the
      Mediterranean Sea coast. The results revealed that the black-sand beach deposits
      could be differentiated according to their total-count (TC) radioactivity into
      five normally distributed interpreted radiometric lithologic (IRL) units denoted
      by U1, U2, U3, U4 and U5. The computed characteristic TC radiometric statistics
      of these five IRL units range from 4.67  to 9.96 Ur for their individual
      arithmetic means. The computed arithmetic means for the three radioelements K, eU
      and eTh reach 0.46 %, 2.25 and 6.17 ppm, respectively for the whole study area.
      Monitoring the environmental effects of radioelement concentrations on the study
      area showed that the mean natural equivalent radiation dose rate from the
      terrestrial gamma-radiation of the whole area attains 0.33 mSv y(-1). This
      average value remains on the safe side and within the maximum permissible safe
      radiation dose (<1.0 mSv y(-1)) without harm to the individual, except at three
      scattered points reaching more than these values. Some of the local inhabitants
      in the region sometimes use black sands as a building material. Consequently,
      they are not recommended for use as building materials, because the inhabitants
      will, then, receive a relatively high radioactive dose generated mainly by
      monazite and zircon minerals, two of the main constituents of black sands.

PMID- 22869820
TI  - Quantifying pulmonary regurgitation and right ventricular function in surgically
      repaired tetralogy of Fallot: a comparative analysis of echocardiography and
      magnetic resonance imaging.
AB  - BACKGROUND: Patients with repaired tetralogy of Fallot are monitored for
      pulmonary regurgitation (PR) and right ventricular (RV) function. We sought to
      compare measures of PR and RV function on echocardiogram to those on cardiac
      magnetic resonance (CMR) and to develop a new tool for assessing PR by
      echocardiogram. METHODS AND RESULTS: Patients with repaired tetralogy of Fallot
      (n=143; 12.5+/-3.2 years) had an echocardiogram and CMR within 3 months of each
      other. On echocardiogram, RV function was assessed by (1) Doppler tissue imaging
      of the RV free wall and (2) myocardial performance index. The ratio of diastolic
      and systolic time-velocity integrals measured by Doppler of the main pulmonary
      artery was calculated. CMR variables included RV ejection fraction, RV volumes,
      and pulmonary regurgitant fraction (RF). Pulmonary regurgitation was graded as
      mild (RF<20%), moderate (RF=20-40%), and severe (RF>40%). On CMR, RF was 34+17%
      and RV ejection fraction was 61+8%. Echocardiography had good sensitivity
      identifying cases with RF>20% (sensitivity 97%; 95% CI: 92-99%) but overestimated
      the amount of PR when RF<20% (false-positive rate 36%; 95% CI: 18-57%). The
      diastolic and systolic time-velocity integrals on echocardiogram showed moderate
      correlation with RF on CMR (R=0.60; P<0.0001). On CMR, RF of 20% and 40%
      corresponded with a diastolic and systolic time-velocity integral of 0.49 (95%
      CI: 0.44-0.56) and 0.72 (95% CI: 0.68-0.76), respectively. RV myocardial
      performance index correlated modestly with RV ejection fraction (r=-0.33;
      P<0.001). CONCLUSIONS: This study suggests that the diastolic and systolic time
      velocity integrals ratio may make a modest contribution to the overall assessment
      of PR in patients with repaired tetralogy of Fallot and warrants further
      investigation. However, echocardiography continues to have a limited ability to
      quantify PR and RV function as compared with CMR.

PMID- 22869821
TI  - Global strain in severe aortic valve stenosis: relation to clinical outcome after
      aortic valve replacement.
AB  - BACKGROUND: Global longitudinal systolic strain (GLS) is often reduced in aortic
      stenosis despite normal ejection fraction. The importance of reduced preoperative
      GLS on long-term outcome after aortic valve replacement is unknown. METHODS AND
      RESULTS: A total of 125 patients with severe aortic stenosis and ejection
      fraction >40% scheduled for aortic valve replacement were evaluated
      preoperatively and divided into 4 groups according to GLS quartiles. Patients
      were followed up for 4 years. The primary end points were major adverse cardiac
      events (MACEs) defined as cardiovascular mortality and cardiac hospitalization
      because of worsening of heart failure; the secondary end point was cardiovascular
      mortality. MACE and cardiac mortality were significantly increased in patients
      with lower GLS. Estimated 5-year MACE was increased: first quartile 19% (n=6) /
      second quartile 20% (n=6) / third quartile 35% (n=11) / fourth quartile 49%
      (n=15); P=0.04. Patients with increased age, left ventricular hypertrophy, and
      left atrial dilatation were at increased risk. In Cox regression analysis, after
      correcting for standard risk factors and ejection fraction, GLS was found to be
      significantly associated with cardiac morbidity and mortality. In a stepwise Cox
      model with forward selection, GLS was the sole independent predictor: hazard
      ratio=1.13 (95% confidence interval, 1.02-1.25), P=0.04. Comparing the overall
      log likelihood chi(2) of the predictive power of the multivariable model
      containing GLS was statistically superior to models based on EuroScore, history
      with ischemic heart disease, and ejection fraction. CONCLUSIONS: In patients with
      symptomatic severe aortic stenosis undergoing aortic valve replacement, reduced
      GLS provides important prognostic information beyond standard risk factors.

PMID- 22869822
TI  - Comparative performance of seven long-running telemedicine networks delivering
      humanitarian services.
AB  - Seven long-running telemedicine networks were surveyed. The networks provided
      humanitarian services (clinical and educational) in developing countries, and had
      been in operation for periods of 5-15 years. The number of experts serving each
      network ranged from 15 to 513. The smallest network had a total of 10 requesters
      and the largest one had more than 500 requesters. The networks operated in nearly
      60 countries. The seven networks managed a total of 1857 cases in 2011, i.e. an
      average of 265 cases per year per network. There was a significant growth in
      total activity, amounting to 100.3 cases per year during the 15 year study
      period. In 2011, network activity was 50-700 teleconsultations per network. There
      were clear differences in the patterns of activity, with some networks managing
      an increasing caseload, and others managing a slowly reducing caseload. The seven
      networks had published a total of 44 papers listed in Medline which summarized
      the evidence resulting from the delivery of services by telemedicine. There was a
      dearth of information about clinical and cost-effectiveness. Nevertheless, the
      services were widely appreciated by referring doctors, considered to be
      clinically useful, and there were indications that clinical outcomes for
      telemedicine patients were often improved. Despite a lack of formal evidence, the
      present study suggests that telemedicine can provide clinically useful services
      in developing countries.

PMID- 22869824
TI  - Maternal HIV infection and vertical transmission of pathogenic bacteria.
AB  - BACKGROUND: HIV-exposed newborns may be at higher risk of sepsis because of
      immune system aberrations, impaired maternal antibody transfer and altered
      exposure to pathogenic bacteria. METHODS: We performed a secondary analysis of a
      study (clinicaltrials.gov, number NCT00136370) conducted between April 2004 and
      October 2007 in South Africa. We used propensity score matching to evaluate the
      association between maternal HIV infection and (1) vaginal colonization with
      bacterial pathogens; (2) vertical transmission of pathogens to the newborn; and
      (3) sepsis within 3 days of birth (EOS) or between 4-28 days of life (LOS).
      RESULTS: Colonization with group B Streptococcus (17% vs 23%, P = .0002),
      Escherichia coli (47% vs 45%, P = .374), and Klebsiella pneumoniae (7% vs 10%, P
      = .008) differed modestly between HIV-infected and uninfected women, as did
      vertical transmission rates. Maternal HIV infection was not associated with
      increased risk of neonatal EOS or LOS, although culture-confirmed EOS was >3
      times higher among HIV-exposed infants (P = .05). When compared with HIV
      unexposed, neonates, HIV-exposed, uninfected neonates (HEU) had a lower risk of
      EOS (20.6 vs 33.7 per 1000 births; P = .046) and similar rate of LOS (5.8 vs 4.1;
      P = .563). HIV-infected newborns had a higher risk than HEU of EOS (134 vs 21.5;
      P < .0001) and LOS (26.8 vs 5.6; P = .042). CONCLUSIONS: Maternal HIV infection
      was not associated with increased risk of maternal bacterial colonization,
      vertical transmission, EOS, or LOS. HIV-infected neonates, however, were at
      increased risk of EOS and LOS.

PMID- 22869825
TI  - Pediatric minimally invasive surgery: laparoscopy and thoracoscopy in infants and
      children.
AB  - This article discusses the potential benefits and challenges of minimally
      invasive surgery for infants and small children, and discusses why pediatric
      minimally invasive surgery is not yet the surgical default or standard of care.
      Minimally invasive methods offer advantages such as smaller incisions, decreased
      risk of infection, greater surgical precision, decreased cost of care, reduced
      length of stay, and better clinical information. But none of these benefits comes
      without cost, and these costs, both monetary and risk-based, rise
      disproportionately with the declining size of the patient. In this review, we
      describe recent progress in minimally invasive surgery for infants and children.
      The evidence for the large benefits to the patient will be presented, as well as
      the considerable, sometimes surprising, mechanical and physiological challenges
      surgeons must manage.

PMID- 22869823
TI  - Prospective multicenter study of children with bronchiolitis requiring mechanical
      ventilation.
AB  - OBJECTIVE: To identify factors associated with continuous positive airway
      pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We
      performed a 16-center, prospective cohort study of hospitalized children aged <2
      years with bronchiolitis. For 3 consecutive years from November 1 until March 31,
      beginning in 2007, researchers collected clinical data and a nasopharyngeal
      aspirate from study participants. We oversampled children from the ICU. Samples
      of nasopharyngeal aspirate were tested by polymerase chain reaction for 18
      pathogens. RESULTS: There were 161 children who required CPAP and/or intubation.
      The median age of the overall cohort was 4 months; 59% were male; 61% white, 24%
      black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation,
      the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence
      interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1
      1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began
      <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95%
      CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions
      (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI
      2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80.
      CONCLUSIONS: In this multicenter study of children hospitalized with
      bronchiolitis, we identified several demographic, historical, and clinical
      factors that predicted the use of CPAP and/or intubation, including children born
      to mothers who smoked during pregnancy. We also identified a novel subgroup of
      children who required mechanical respiratory support <1 day after respiratory
      symptoms began.

PMID- 22869827
TI  - Vitamin D deficiency in critically ill children: a roadmap to interventional
      research.

PMID- 22869826
TI  - The impact of a healthy media use intervention on sleep in preschool children.
AB  - BACKGROUND: Although observational studies have consistently reported an
      association between media use and child sleep problems, it is unclear whether the
      relationship is causal or if an intervention targeting healthy media use can
      improve sleep in preschool-aged children. METHODS: We conducted a randomized
      controlled trial of a healthy media use intervention in families of children aged
      3 to 5 years. The intervention encouraged families to replace violent or age
      inappropriate media content with quality educational and prosocial content,
      through an initial home visit and follow-up telephone calls over 6 months. Sleep
      measures were derived from the Child Sleep Habits Questionnaire and were
      collected at 6, 12, and 18 months after baseline; repeated-measures regression
      analyses were used. RESULTS: Among the 565 children analyzed, the most common
      sleep problem was delayed sleep-onset latency (38%). Children in the intervention
      group had significantly lower odds of "any sleep problem" at follow-up in the
      repeated-measures analysis (odds ratio = 0.36; 95% confidence interval: 0.16 to
      0.83), with a trend toward a decrease in intervention effect over time (P = .07).
      Although there was no significant effect modification detected by baseline sleep
      or behavior problems, gender, or low-income status, there was a trend (P = .096)
      toward an increased effect among those with high levels of violence exposure at
      baseline. CONCLUSIONS: The significant effects of a healthy media use
      intervention on child sleep problems in the context of a randomized controlled
      trial suggest that the previously reported relationship between media use and
      child sleep problems is indeed causal in nature.

PMID- 22869828
TI  - Haemophilus influenzae type b disease and vaccine booster dose deferral, United
      States, 1998-2009.
AB  - BACKGROUND: Since the introduction of effective vaccines, the incidence of
      invasive Haemophilus influenzae type b (Hib) disease among children <5 years of
      age has decreased by 99% in the United States. In response to a limited vaccine
      supply that began in 2007, Hib booster doses were deferred for 18 months.
      METHODS: We reviewed national passive and active surveillance (demographic and
      serotype) and vaccination status data for invasive H. influenzae disease in
      children aged <5 years before (1998-2007) and during (2008-2009) the vaccine
      shortage years to assess the impact of the vaccine deferral on Hib disease. We
      estimated the average annual number of Hib cases misclassified as unknown (not
      completed or missing) serotype. RESULTS: From 1998 to 2007 and 2008 to 2009, the
      annual average incidence of Hib disease per 100000 population was 0.2 and 0.18,
      respectively; no significant difference in incidence was found by age group,
      gender, or race. Among Hib cases in both time periods, most were unvaccinated or
      too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib
      cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown
      serotype. CONCLUSIONS: The booster deferral did not have a significant impact on
      the burden of invasive Hib disease in children <5 years of age. Continued
      surveillance and serotype data are important to monitor changes in Hib incidence,
      especially during vaccine deferrals. Hib booster deferral is a reasonable short
      term approach to a Hib vaccine shortage.

PMID- 22869830
TI  - Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized,
      placebo-controlled study.
AB  - OBJECTIVES: To compare the effects of a single nocturnal dose of 3 honey products
      (eucalyptus honey, citrus honey, or labiatae honey) to placebo (silan date
      extract) on nocturnal cough and difficulty sleeping associated with childhood
      upper respiratory tract infections (URIs). METHODS: A survey was administered to
      parents on 2 consecutive days, first on the day of presentation, when no
      medication had been given the previous evening, and the following day, when the
      study preparation was given before bedtime, based on a double-blind randomization
      plan. Participants included 300 children aged 1 to 5 years with URIs, nocturnal
      cough, and illness duration of <= 7 days from 6 general pediatric community
      clinics. Eligible children received a single dose of 10 g of eucalyptus honey,
      citrus honey, labiatae honey, or placebo administered 30 minutes before bedtime.
      Main outcome measures were cough frequency, cough severity, bothersome nature of
      cough, and child and parent sleep quality. RESULTS: In all 3 honey products and
      the placebo group, there was a significant improvement from the night before
      treatment to the night of treatment. However, the improvement was greater in the
      honey groups for all the MAIN OUTCOME MEASURES:  CONCLUSIONS: Parents rated the
      honey products higher than the silan date extract for symptomatic relief of their
      children's nocturnal cough and sleep difficulty due to URI. Honey may be a
      preferable treatment for cough and sleep difficulty associated with childhood
      URI.

PMID- 22869829
TI  - Montelukast for children with obstructive sleep apnea: a double-blind, placebo
      controlled study.
AB  - OBJECTIVES: Children with nonsevere obstructive sleep apnea (OSA) benefit from
      alternative therapeutic interventions such as leukotriene modifiers. We
      hypothesized that montelukast might improve OSA in children. We tested this
      hypothesis in a double-blind, randomized, placebo-controlled fashion. METHODS: Of
      50 possible candidates, we recruited 46 children with polysomnographically
      diagnosed OSA. In this prospective, double-blind, randomized trial, children
      received daily oral montelukast at 4 or 5 mg (<6 or >6 years of age,
      respectively) or placebo for 12 weeks. Polysomnographic assessments, parent
      questionnaires, and radiographs to assess adenoid size were performed before and
      after therapy. RESULTS: Compared with the 23 children that received placebo, the
      23 children that received montelukast showed significant improvements in
      polysomnographic measures of respiratory disturbance (obstructive apnea index),
      children's symptoms, and adenoid size. The obstructive apnea index decreased by
      >50% in 65.2% of treated children. No attrition or side effects occurred.
      CONCLUSIONS: A 12-week treatment with daily, oral montelukast effectively reduced
      the severity of OSA and the magnitude of the underlying adenoidal hypertrophy in
      children with nonsevere OSA.

PMID- 22869831
TI  - Successful treatment of pallid breath-holding spells with fluoxetine.
AB  - Pallid breath-holding (PBH) is a childhood condition that presents with recurrent
      syncope. Although typically benign, severe cases can lead to asystole and anoxic
      seizures. Previous studies have advocated pacemaker placement to abbreviate
      symptoms. This was a retrospective study of patients treated with fluoxetine for
      PBH spells. Clinical response, side effects and avoidance of pacemaker
      implantation were reviewed in six patients (12-60 months) treated with fluoxetine
      for PBH. Patients were referred because of concern of arrhythmia and failed
      medical treatment strategies. Two patients had previously implanted loop
      recorders, 5 patients had documented episodes of asystole, and 2 patients had
      generalized seizures. Fluoxetine resulted in alleviation of syncope in 5 of 6
      patients. Time to symptomatic improvement symptoms ranged from 2 days to 1 month
      (median, 2 weeks). Median duration of treatment with fluoxetine was 12 months (12
      24 months). One patient demonstrated no improvement and had a pacemaker
      implanted. There were no reported side effects to fluoxetine. Fluoxetine can be
      used to treat childhood PBH spells and may obviate the need for permanent pacing
      in a significant subset of this population. Considering its safe side-effect
      profile it is a worthwhile first-line agent to treat this disorder.

PMID- 22869832
TI  - Improving newborn screening follow-up in pediatric practices: quality improvement
      innovation network.
AB  - OBJECTIVE: To implement a 6-month quality improvement project in 15 primary care
      pediatric practices to improve short-term newborn screening (NBS) follow-up.
      METHODS: At the start of the project, each practice completed a survey to
      evaluate office systems related to NBS and completed a chart audit. Practice
      teams were provided information about NBS and trained in quality-improvement
      methods, and then implemented changes to improve care. Monthly chart audits over
      a 6-month period were completed to assess change. RESULTS: At baseline, almost
      half of practices completed assessment of infants for NBS; after 6 months, 80% of
      practices completed assessment of all infants. Only 2 practices documented all in
      range results and shared them with parents at baseline; by completion, 10 of 15
      practices documented and shared in-range results for >= 70% of infants. Use of
      the American College of Medical Genetics ACTion sheets, a decision support tool,
      increased from 1 of 15 practices at baseline to 7 of 15 at completion.
      CONCLUSIONS: Practices were successful in improving NBS processes, including
      assessment, documentation, and communication with families. Providers perceived
      no increase in provider time at first visit, 2- to 4-week visit, or during first
      contact with the family of an infant with an out-of-range result after
      implementation of improved processes. Primary care practices increased their use
      of decision support tools after the project.

PMID- 22869833
TI  - Copper deficiency presenting as metabolic bone disease in extremely low birth
      weight, short-gut infants.
AB  - Copper deficiency can cause bone lesions in infants, which might be confused with
      child abuse. Two extremely low birth weight preterm infants had complicated
      medical courses requiring prolonged parenteral nutrition for short-gut syndrome,
      which led to the development of cholestasis. Both had spent their entire lives in
      the hospital. They had been on prolonged ventilator support for chronic lung
      disease. They developed signs of copper deficiency between 5 and 6 months of age,
      initially raising child abuse concerns. Musculoskeletal discomfort led to the
      recognition of radiographic findings of metabolic bone disease. Included were
      osteoporosis, metaphyseal changes, and physeal disruptions. Copper levels were
      low; both low copper parenteral nutrition and gut losses from refeeding diarrhea
      likely contributed to their deficiency. Therapeutic supplementation with copper
      corrected their deficits and clinical and radiologic findings. The information
      from these cases, in particular, their radiologic findings, indicate the need to
      monitor copper status in at-risk premature infants. These findings may aid
      prevention and earlier recognition of copper deficiency. Their specific
      radiologic and clinical findings should aid differentiation of such children from
      abused infants.

PMID- 22869834
TI  - Culturally tailored, family-centered, behavioral obesity intervention for Latino
      American preschool-aged children.
AB  - OBJECTIVE: To test the effect of a culturally tailored, family-centered, short
      term behavioral intervention on BMI in Latino-American preschool-aged children.
      METHODS: In a randomized controlled trial, 54 parent-child dyads were allocated
      to the intervention and 52 dyads were allocated to an alternative school
      readiness program as the control condition. Parent-child dyads were eligible if
      the parent self-defined Latino, was at least 18 years old, had a 2- to 6-year-old
      child not currently enrolled in another healthy lifestyle program, had a valid
      telephone number, and planned on remaining in the city for the next 6 months. The
      Salud Con La Familia (Health with the Family) program consisted of 12 weekly 90
      minute skills-building sessions designed to improve family nutritional habits and
      increase physical activity. Both programs were conducted in a community
      recreation center serving an urban neighborhood of mostly Spanish-speaking
      residents. RESULTS: Forty-two percent of participating preschool-aged children
      were overweight or obese. Controlling for child age, gender, and baseline BMI,
      the effect of the treatment condition on postintervention absolute BMI was B = 
      0.59 (P < .001). The intervention effect seemed to be strongest for obese
      children. CONCLUSIONS: A skills-building, culturally tailored intervention
      involving parent-child dyads changed short-term early growth patterns in these
      Latino-American preschool-aged children. Examining long-term effects would be a
      prudent next step.

PMID- 22869835
TI  - Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus
      arteriosus.
AB  - BACKGROUND: Experimental studies suggest that platelet-triggered ductal sealing
      is critically involved in definite ductus arteriosus closure. Whether
      thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in
      humans is controversial. This was a retrospective study of 1350 very low birth
      weight (VLBW; <1500 g) infants, including 592 extremely low birth weight (ELBW;
      <1000 g) infants. METHODS: All infants who had a platelet count in the first 24
      hours after birth and an echocardiogram performed on day of life 4 to 5 were
      included. The incidence of thrombocytopenia was analyzed in infants with and
      without PDA, and in those who did or did not undergo PDA intervention. The impact
      of thrombocytopenia, gestational age, birth weight, gender, and sepsis on PDA was
      determined by receiver operating characteristic curve, odds ratio, and regression
      analyses. RESULTS: Platelet numbers within the first 24 hours after birth did not
      differ between VLBW/ELBW infants with and without spontaneous ductal closure.
      Platelet numbers were not associated with subsequent PDA treatment. Low platelet
      counts were not related to failure of pharma-cologic PDA treatment and the need
      for subsequent surgical ligation. Lower gestational age or birth weight, male
      gender, and sepsis were linked to the presence of PDA in VLBW infants on day of
      life 4 to 5. CONCLUSIONS: Thrombocytopenia in the first 24 hours after birth was
      not associated with PDA in this largest VLBW/ELBW infant cohort studied to date.
      Impaired platelet function, due to immaturity and critical illness, rather than
      platelet number, might play a role in ductus arteriosus patency.

PMID- 22869837
TI  - The association of vitamin D status with pediatric critical illness.
AB  - OBJECTIVES: Vitamin D is a pleiotropic hormone important for the proper
      functioning of multiple organ systems. It has been hypothesized that vitamin D
      deficiency could contribute to or worsen outcomes in critical illness. The study
      objective was to determine the prevalence of vitamin D deficiency, risk factors
      for its presence, and potential association with clinically relevant outcomes in
      critically ill children. METHODS: A prospective cohort study, conducted from 2005
      to 2008 in 6 tertiary-care PICUs in Canada. Data and biological samples from 326
      critically ill children up to 17 years of age were available for analysis. Total
      serum 25 hydroxyvitamin D or 25(OH)D was measured by using liquid chromatography
      mass spectrometry. RESULTS: The prevalence of 25(OH)D <50 nmol/L was 69% (95%
      confidence interval, 64-74), and 23% (95% confidence interval, 19-28) for 25(OH)D
      between 50 to 75 nmol/L. Lower levels were associated with hypocalcemia,
      catecholamine utilization, and significant fluid bolus administration. Vitamin D
      deficiency was independently associated with a longer PICU length of stay (+1.92
      days, P = .03) and increasing severity of illness as determined by the Pediatric
      Risk of Mortality score with every additional point increasing the likelihood of
      being vitamin D deficient by 8% (P = .005). CONCLUSIONS: This study provides
      evidence that vitamin D deficiency is both common among critically ill children
      and associated with greater severity of critical illness. Further research will
      determine whether targeted vitamin D supplementation or rapid restoration will
      improve outcome.

PMID- 22869836
TI  - Vitamin D deficiency in critically ill children.
AB  - OBJECTIVE: Vitamin D influences cardiovascular and immune function. We aimed to
      establish the prevalence of vitamin D deficiency in critically ill children and
      identify factors influencing admission 25-hydroxy vitamin D (25(OH)D) levels. We
      hypothesized that levels would be lower with increased illness severity and in
      children with serious infections. METHODS: Participants were 511 severely or
      critically ill children admitted to the PICU from November 2009 to November 2010.
      Blood was collected near PICU admission and analyzed for 25(OH)D concentration by
      using Diasorin radioimmunoassay. RESULTS: We enrolled 511 of 818 (62.5%) eligible
      children. The median 25(OH)D level was 22.5 ng/mL; 40.1% were 25(OH)D deficient
      (level <20 ng/mL). In multivariate analysis, age and race were associated with
      25(OH)D deficiency; summer season, vitamin D supplementation, and formula intake
      were protective; 25(OH)D levels were not lower in the 238 children (46.6%)
      admitted with a life-threatening infection, unless they had septic shock (n = 51,
      10.0%) (median 25(OH)D level 19.2 ng/mL; P = .0008). After adjusting for factors
      associated with deficiency, lower levels were associated with higher admission
      day illness severity (odds ratio 1.19 for a 1-quartile increase in Pediatric Risk
      of Mortality III score per 5 ng/mL decrease in 25(OH)D, 95% confidence interval
      1.10-1.28; P < .0001). CONCLUSIONS: We found a high rate of vitamin D deficiency
      in critically ill children. Given the roles of vitamin D in bone development and
      immunity, we recommend screening of those critically ill children with risk
      factors for vitamin D deficiency and implementation of effective repletion
      strategies.

PMID- 22869838
TI  - Malarial acute kidney injury in a paediatric intensive care unit.
AB  - Acute kidney injury (AKI) is a serious complication of malaria which has a very
      high mortality rate. A retrospective analysis of medical record data of children
      treated for malarial AKI in a paediatric intensive care unit (PICU) was performed
      in order to evaluate the incidence, poor prognostic factors and outcome of AKI
      with malaria. Eighteen (48.6%) malarial patients had AKI (11 Plasmodium vivax
      positive, six P. falciparum positive and one mixed infection) with a male-to
      female ratio of 1:2. The mean age was 75 +/- 32 months (range, 1 month to 10
      years). Oliguria was present in 61.1% and 55.5% required renal replacement
      therapy. Mortality was noted in 33.3% of patients and full recovery was achieved
      in 50% of patients. Oliguria, shock, central nervous system involvement,
      jaundice, disseminated intravascular coagulopathy and acute respiratory distress
      syndrome emerged as bad prognostic factors in simple univariate analysis. Malaria
      patients with and without AKI differ significantly in terms of shock, ventilator
      requirement, mortality and length of PICU stay.

PMID- 22869839
TI  - Bleeding after initiation of multiple antithrombotic drugs, including triple
      therapy, in atrial fibrillation patients following myocardial infarction and
      coronary intervention: a nationwide cohort study.
AB  - BACKGROUND: Uncertainty remains over optimal antithrombotic treatment of patients
      with atrial fibrillation presenting with myocardial infarction and/or undergoing
      percutaneous coronary intervention. We investigated the risk and time frame for
      bleeding following myocardial infarction/percutaneous coronary intervention in
      patients with atrial fibrillation according to antithrombotic treatment. METHODS
      AND RESULTS: Patients with atrial fibrillation and admitted with myocardial
      infarction or for percutaneous coronary intervention between 2000 and 2009 (11
      480 subjects, mean age 75.6 years [SD +/-10.3], males 60.9%) were identified by
      individual level linkage of nationwide registries in Denmark. Fatal or nonfatal
      (requiring hospitalization) bleeding was determined according to antithrombotic
      treatment regimen: triple therapy (TT) with vitamin K antagonist
      (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with
      aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard
      ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded
      (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3
      bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual
      antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90
      360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was
      increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No
      significant difference in thromboembolic risk was observed for TT versus
      VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40). CONCLUSIONS: High risk of
      bleeding is immediately evident with TT after myocardial infarction/percutaneous
      coronary intervention in patients with atrial fibrillation. A continually
      elevated risk associated with TT indicates no safe therapeutic window, and TT
      should only be prescribed after thorough bleeding risk assessment of patients.

PMID- 22869840
TI  - Acute coronary syndrome in patients with atrial fibrillation: what is the
      benefit/risk profile of triple antithrombotic therapy?

PMID- 22869841
TI  - Implantable cardioverter-defibrillators have reduced the incidence of
      resuscitation for out-of-hospital cardiac arrest caused by lethal arrhythmias.
AB  - BACKGROUND: Over the last decades, a gradual decrease in ventricular fibrillation
      (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac
      arrest (OHCA) has been noted. We sought to establish the contribution of
      implantable cardioverter-defibrillator (ICD) therapy to this decline. METHODS AND
      RESULTS: Using a prospective database of all OHCA resuscitation in the province
      North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we
      collected data on all patients in whom resuscitation for OHCA was attempted in
      2005-2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with
      VF OHCA incidence data during 1995-1997, collected in a similar way. We also
      collected ICD interrogations of all ICD patients from North Holland and
      identified all appropriate ICD shocks in 2005-2008; we calculated the number of
      prevented VF OHCA episodes, considering that only part of the appropriate shocks
      would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100
      000 in 1995-1997 to 17.4/100 000 in 2005-2008 (P<0.001). Non-VF OHCA increased
      from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined
      from 63% to 47%. In 2005-2008, 1972 ICD patients received 977 shocks. Of these
      shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these
      339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA,
      corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF
      OHCA incidence. CONCLUSIONS: The incidence of VF OHCA decreased over the last 10
      years in North Holland. ICD therapy explained a decrease of 1.2/100 000
      inhabitants per year, corresponding with 33% of the observed decline in VF OHCA.

PMID- 22869842
TI  - Out-of-hospital cardiac arrest: getting beyond the tip of the iceberg.

PMID- 22869843
TI  - Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine
      Society clinical practice guideline.
AB  - OBJECTIVE: The aim was to update the guidelines for the management of thyroid
      dysfunction during pregnancy and postpartum published previously in 2007. A
      summary of changes between the 2007 and 2012 version is identified in the
      Supplemental Data (published on The Endocrine Society's Journals Online web site
      at http://jcem.endojournals.org). EVIDENCE: This evidence-based guideline was
      developed according to the U.S. Preventive Service Task Force, grading items
      level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of
      net benefit (benefits minus harms) as well as the Grading of Recommendations,
      Assessment, Development, and Evaluation (GRADE) system to describe both the
      strength of recommendations and the quality of evidence. CONSENSUS PROCESS: The
      guideline was developed through a series of e-mails, conference calls, and one
      face-to-face meeting. An initial draft was prepared by the Task Force, with the
      help of a medical writer, and reviewed and commented on by members of The
      Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American
      Thyroid Society. A second draft was reviewed and approved by The Endocrine
      Society Council. At each stage of review, the Task Force received written
      comments and incorporated substantive changes. CONCLUSIONS: Practice guidelines
      are presented for diagnosis and treatment of patients with thyroid-related
      medical issues just before and during pregnancy and in the postpartum interval.
      These include evidence-based approaches to assessing the cause of the condition,
      treating it, and managing hypothyroidism, hyperthyroidism, gestational
      hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition,
      postpartum thyroiditis, and screening for thyroid disease. Indications and side
      effects of therapeutic agents used in treatment are also presented.

PMID- 22869844
TI  - Approach to the patient with anaplastic thyroid carcinoma.
AB  - Anaplastic thyroid carcinoma is the least common but most lethal of thyroid
      cancers. All patients are classified as stage IV, with the primary lesion
      restricted to the thyroid gland in stage IVA; locoregional lymph nodes may exist
      in IVA/IVB; and IVC disease is defined by distant metastases. Prognosis is highly
      dependent on disease extent at presentation, and staging and establishing a plan
      of care must be accomplished quickly. Although almost all studies are biased due
      to their retrospective nature, the most important factors associated with longer
      survival are completeness of surgical resection (achievable in only a minority of
      patients) and high-dose (>40 Gy) external beam radiotherapy (preferably intensity
      modulated radiation therapy). Recent reports suggest that a multimodal approach
      (surgery, radiation, and chemotherapy) is beneficial. Given the high lethality
      even with apparent local disease, combination systemic therapy (cytotoxics and/or
      targeted agents) may improve outcomes in stage IVA/IVB patients. Newer, more
      effective drug combinations are urgently needed for IVC patients who want
      aggressive therapy. A candid discussion of the prognosis and management options,
      including palliative care/hospice, should be held with the patient and caregiver
      as soon as possible after diagnosis to clarify the patient's preference and
      expectations. Prospective multicenter clinical trials, incorporating molecular
      analyses of tumors, are required if we are to improve survival in anaplastic
      thyroid carcinoma.

PMID- 22869845
TI  - Optimal care of the pregnant woman with thyroid disease.

PMID- 22869846
TI  - Treatment of recurrent or persistent cervical node metastases in differentiated
      thyroid cancer: deceptively simple options.

PMID- 22869847
TI  - Mechanism of action of DPP-4 inhibitors--new insights.

PMID- 22869848
TI  - Thyroid dysfunction and pregnancy: where are we five years later?

PMID- 22869849
TI  - When thyroidologists agree to disagree: comments on the 2012 Endocrine Society
      pregnancy and thyroid disease clinical practice guideline.

PMID- 22869853
TI  - The Endocrine Society 2012 Laureate Awards.

PMID- 22869856
TI  - Patient guide to detecting and treating hyperthyroidism before, during, and after
      pregnancy.

PMID- 22869858
TI  - Management of deep vein thrombosis of the upper extremity.

PMID- 22869859
TI  - Laparoscopic adjustable gastric banding and other devices for the management of
      obesity.

PMID- 22869860
TI  - Suction of the left internal mammary artery graft into a pleural drain visualized
      by computerized tomography.

PMID- 22869857
TI  - The assessment of endothelial function: from research into clinical practice.

PMID- 22869861
TI  - Unusual pseudotumoral right atrial involvement in Listeria monocytogenes
      septicemia.

PMID- 22869863
TI  - Letter by Chen and Zhang regarding article, "mechanisms of myocardial infarction
      in women without angiographically obstructive coronary artery disease".

PMID- 22869864
TI  - Letter by Ward and Figtree article, "mechanisms of myocardial infarction in women
      without angiographically obstructive coronary artery disease".

PMID- 22869865
TI  - Letter by Burillo-Putze et al regarding article, "acute coronary syndrome and
      khat herbal amphetamine use: an observational report".

PMID- 22869866
TI  - Letter by Aleryani and Al-Akwa regarding article, "Acute coronary syndrome and
      khat herbal amphetamine use: an observational report".

PMID- 22869867
TI  - Letter by Nagelkerke and Conca regarding article, "acute coronary syndrome and
      khat herbal amphetamine use: an observational report".

PMID- 22869868
TI  - Aflibercept in pediatric solid tumors: moving beyond the trap.
AB  - Angiogenesis plays a pivotal role in the growth and metastasis of adult and
      pediatric solid tumors. Clinical investigation of angiogenesis inhibitors is
      currently under way for childhood cancers. While the pediatric study of
      aflibercept provides a proof-of-principle, challenges remain in developing
      clinical endpoints and biomarkers of angiogenesis for pediatric trials.

PMID- 22869870
TI  - Hidden dangers: a cryptic exon disrupts BRCA2 mRNA.
AB  - The first mutation that disrupts BRCA2 mRNA by including a novel, cryptic exon is
      reported in this issue. The mutation lies deep within an intron and would not
      have been detected by conventional screening methods. In the future, more
      mutations may be discovered by direct mRNA analysis.

PMID- 22869869
TI  - Effects of selective checkpoint kinase 1 inhibition on cytarabine cytotoxicity in
      acute myelogenous leukemia cells in vitro.
AB  - PURPOSE: Previous studies have shown that the replication checkpoint, which
      involves the kinases ataxia telangiectasia mutated and Rad3 related (ATR) and
      Chk1, contributes to cytarabine resistance in cell lines. In the present study,
      we examined whether this checkpoint is activated in clinical acute myelogenous
      leukemia (AML) during cytarabine infusion in vivo and then assessed the impact of
      combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in
      vitro. EXPERIMENTAL DESIGN: AML marrow aspirates harvested before and during
      cytarabine infusion were examined by immunoblotting. Human AML lines treated with
      cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint
      activation by immunoblotting, nucleotide incorporation into DNA, and flow
      cytometry. Long-term effects in AML lines, clinical AML isolates, and normal
      myeloid progenitors were assayed using clonogenic assays. RESULTS: Immunoblotting
      revealed increased Chk1 phosphorylation, a marker of checkpoint activation, in
      more than half of Chk1-containing AMLs after 48 hours of cytarabine infusion. In
      human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation
      and S-phase arrest but also markedly increased cytarabine-induced apoptosis.
      Clonogenic assays demonstrated that SCH 900776 enhanced the antiproliferative
      effects of cytarabine in AML cell lines and clinical AML samples at
      concentrations that had negligible impact on normal myeloid progenitors.
      CONCLUSIONS: These results not only provide evidence for cytarabine-induced S
      phase checkpoint activation in AML in the clinical setting, but also show that a
      selective Chk1 inhibitor can overcome the S-phase checkpoint and enhance the
      cytotoxicity of cytarabine. Accordingly, further investigation of the
      cytarabine/SCH 900776 combination in AML appears warranted.

PMID- 22869871
TI  - Cutaneous manifestations of unspecified peripheral T-cell lymphoma may be
      indicative of disease activity and predict response to therapy.

PMID- 22869873
TI  - Graft-versus-host disease: have we solved the problem?

PMID- 22869872
TI  - Targeting the hepatocyte growth factor-cMET axis in cancer therapy.
AB  - The hepatocyte growth factor (HGF) and its receptor, the transmembrane tyrosine
      kinase cMET, promote cell proliferation, survival, motility, and invasion as well
      as morphogenic changes that stimulate tissue repair and regeneration in normal
      cells but can be co-opted during tumor growth. MET overexpression, with or
      without gene amplification, has been reported in a variety of human cancers,
      including breast, lung, and GI malignancies. Furthermore, high levels of HGF
      and/or cMET correlate with poor prognosis in several tumor types, including
      breast, ovarian, cervical, gastric, head and neck, and non-small-cell lung
      cancers. Gene amplification and protein overexpression of cMET drive resistance
      to epidermal growth factor receptor family inhibitors, both in preclinical models
      and in patients. It is increasingly apparent that the HGF-cMET axis signaling
      network is complex, and rational combinatorial therapy is needed for optimal
      clinical efficacy. Better understanding of HGF-cMET axis signaling and the
      mechanism of action of HGF-cMET inhibitors, along with the identification of
      biomarkers of response and resistance, will lead to more effective targeting of
      this pathway for cancer therapy.

PMID- 22869874
TI  - Tumor necrosis factor alpha as a master regulator of inflammation in Erdheim
      Chester disease: rationale for the treatment of patients with infliximab.

PMID- 22869875
TI  - KRAS wild-type lung cancer: a moving target in an era of genotype migration.

PMID- 22869876
TI  - Making advances in first-line chronic lymphocytic leukemia treatment.

PMID- 22869877
TI  - Do socially deprived urban areas have lesser supplies of cancer care services?
AB  - PURPOSE: Area social deprivation is associated with unfavorable health outcomes
      of residents across the full clinical course of cancer from the stage at
      diagnosis through survival. We sought to determine whether area social factors
      are associated with the area health care supply. PATIENTS AND METHODS: We studied
      the area supply of health services required for the provision of guideline
      recommended care for patients with breast cancer and colorectal cancer (CRC) in
      each of the following three distinct clinical domains: screening, treatment, and
      post-treatment surveillance. We characterized area social factors in 3,096 urban
      zip code tabulation areas by using Census Bureau data and the health care supply
      in the corresponding 465 hospital service areas by using American Hospital
      Association, American Medical Association, and US Food and Drug Administration
      data. In two-level hierarchical models, we assessed associations between social
      factors and the supply of health services across areas. RESULTS: We found no
      clear associations between area social factors and the supply of health services
      essential to the provision of guideline recommended breast cancer and CRC care in
      urban areas. The measures of health service included the supply of physicians who
      facilitate screening, treatment, and post-treatment care and the supply of
      facilities required for the same services. CONCLUSION: Because we found that the
      supply of types of health care required for the provision of guideline
      recommended cancer care for patients with breast cancer and CRC did not vary with
      markers of area socioeconomic disadvantage, it is possible that previously
      reported unfavorable breast cancer and CRC outcomes among individuals living in
      impoverished areas may have occurred despite an apparent adequate area health
      care supply.

PMID- 22869878
TI  - Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis
      of the international peripheral T-cell lymphoma project.
AB  - PURPOSE: The International Peripheral T-Cell Lymphoma Project was undertaken to
      better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas.
      PATIENTS AND METHODS: Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed
      according to the 2001 WHO criteria by a central review process consisting of
      panels of expert hematopathologists. Clinical, pathologic, immunophenotyping,
      treatment, and survival data were correlated. RESULTS: Of 1,314 patients, 243
      (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy
      was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was
      observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred
      in 13% and 30% of patients, respectively. Five-year overall and failure-free
      survivals were 33% and 18%, respectively. At presentation, prognostic models were
      evaluated, including the standard International Prognostic Index, which comprised
      the following factors: age >= 60 years, stages III to IV disease, lactic
      dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance
      status (PS) >= 2; the Prognostic Index for Peripheral T-Cell Lymphoma,
      comprising: age >= 60 years, PS >= 2, LDH > normal, and bone marrow involvement;
      and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years,
      PS >= 2, ENSs > one, B symptoms, and platelet count < 150 * 10(9)/L. The
      simplified PIAI had a low-risk group (zero to one factors), with 5-year survival
      of 44%, and a high-risk group (two to five factors), with 5-year survival of 24%
      (P = .0065). CONCLUSION: AITL is a rare clinicopathologic entity characterized by
      an aggressive course and dismal outcome with current therapies.

PMID- 22869879
TI  - Validation of a prognostic model and the impact of mutations in patients with
      lower-risk myelodysplastic syndromes.
AB  - PURPOSE: A subset of patients with myelodysplastic syndromes (MDS) who are
      predicted to have lower-risk disease as defined by the International Prognostic
      Scoring System (IPSS) demonstrate more aggressive disease and shorter overall
      survival than expected. The identification of patients with greater-than
      predicted prognostic risk could influence the selection of therapy and improve
      the care of patients with lower-risk MDS. PATIENTS AND METHODS: We performed an
      independent validation of the MD Anderson Lower-Risk Prognostic Scoring System
      (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS
      and examined bone marrow samples from these patients for mutations in 22 genes,
      including SF3B1, SRSF2, U2AF1, and DNMT3A. RESULTS: The LR-PSS successfully
      stratified patients with lower-risk MDS into three risk categories with
      significant differences in overall survival (20% in category 1 with median of
      5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65
      years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11
      years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model.
      Mutations were identified in 71% of all samples, and mutations associated with a
      poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of
      EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival
      independent of the LR-PSS. Only EZH2 mutations retained prognostic significance
      in a multivariable model that included LR-PSS and other mutations (hazard ratio,
      2.90; 95% CI, 1.85 to 4.52). CONCLUSION: Combining the LR-PSS and EZH2 mutation
      status identifies 29% of patients with lower-risk MDS with a worse-than-expected
      prognosis. These patients may benefit from earlier initiation of disease
      modifying therapy.

PMID- 22869880
TI  - Disparities in breast cancer outcomes: receipt of chemotherapy is only part of
      the story.

PMID- 22869881
TI  - Challenge of primary tumor management in patients with stage IV colorectal
      cancer.

PMID- 22869882
TI  - Comparative outcomes of donor graft CD34+ selection and immune suppressive
      therapy as graft-versus-host disease prophylaxis for patients with acute myeloid
      leukemia in complete remission undergoing HLA-matched sibling allogeneic
      hematopoietic cell transplantation.
AB  - PURPOSE: T-cell depletion (TCD) reduces the incidence of graft-versus-host
      disease (GVHD) after hematopoietic cell transplantation (HCT). However, concerns
      about relapse, graft rejection, and variability in technique have limited the
      widespread application of this approach. PATIENTS AND METHODS: Outcomes of 44
      patients receiving HLA-identical sibling TCD grafts using a uniform technique for
      CD34(+) selection as the sole form of immune suppression were compared with
      outcomes of 84 patients receiving T-replete grafts and pharmacologic immune
      suppression therapy (IST). RESULTS: Groups were similar, except for fewer men
      (36% with TCD v 56% with IST) and more frequent use of radiation-containing
      regimens (100% with TCD v 50% with IST) in the CD34-selected TCD cohort. The
      proportion of patients with neutrophil engraftment at day 28 was similar (96%
      with IST and 100% with TCD grafts). The 100-day rates of grade 2 to 4 acute GVHD
      were 39% and 23% with IST and TCD grafts, respectively (P = .07). Corresponding 2
      year rates of chronic GVHD were lower with TCD grafts than IST (19% v 50%,
      respectively; P < .001). There were no differences in rates of graft rejection,
      leukemia relapse, treatment-related mortality, and disease-free and overall
      survival rates. At 1 year, 54% and 12% of patients were still on
      immunosuppression in the IST and TCD cohorts, respectively. TCD was associated
      with a higher GVHD-free survival at 2 years compared with IST (41% v 19%,
      respectively; P = .006). CONCLUSION: These results suggest that TCD via CD34
      selection might lower long-term morbidity as a result of chronic GVHD without
      negatively impacting relapse rates in patients with acute myeloid leukemia.
      Additional prospective studies should be undertaken to definitively address the
      role of TCD in HCT.

PMID- 22869883
TI  - Bortezomib-based graft-versus-host disease prophylaxis in HLA-mismatched
      unrelated donor transplantation.
AB  - PURPOSE: HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell
      transplantation (HSCT) is associated with increased graft-versus-host disease
      (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex
      vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly
      improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory
      properties potentially beneficial for control of GVHD in T-cell-replete HLA
      mismatched transplantation. PATIENTS AND METHODS: We conducted a prospective
      phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib,
      administered once per day on days +1, +4, and +7 after peripheral blood stem-cell
      infusion plus standard tacrolimus and methotrexate in patients with hematologic
      malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients:
      40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or 
      DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up.
      RESULTS: The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95%
      CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI,
      16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and
      relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively.
      Two-year progression-free survival and overall survival were 51% (95% CI, 36% to
      64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA
      mismatched patients experienced rates of NRM, acute and chronic GVHD, and
      survival similar to those of contemporaneous HLA-matched RIC HSCT at our
      institution. Immune recovery, including CD8(+) T-cell and natural killer cell
      reconstitution, was enhanced with bortezomib. CONCLUSION: A novel short-course,
      bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC
      HSCT, can enhance early immune reconstitution, and appears to be suitable for
      prospective randomized evaluation.

PMID- 22869884
TI  - Bendamustine in combination with rituximab for previously untreated patients with
      chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic
      Lymphocytic Leukemia Study Group.
AB  - PURPOSE: We investigated the safety and efficacy of bendamustine and rituximab
      (BR) in previously untreated patients with chronic lymphocytic leukemia (CLL).
      PATIENTS AND METHODS: In all, 117 patients, age 34 to 78 years, 46.2% of patients
      at Binet stage C, and 25.6% of patients age 70 years or older received BR
      chemoimmunotherapy for first-line treatment of CLL. Bendamustine was administered
      at a dose of 90 mg/m(2) on days 1 and 2 combined with 375 mg/m(2) rituximab on
      day 0 of the first course and 500 mg/m(2) on day 1 during subsequent courses for
      up to six courses. RESULTS: Overall response rate was 88.0% (95% CI, 80.7% to
      100.0%) with a complete response rate of 23.1% and a partial response rate of
      64.9%. Ninety percent of patients with del(11q), 94.7% with trisomy 12, 37.5%
      with del(17p), and 89.4% with unmutated IGHV status responded to treatment. After
      a median observation time of 27.0 months, median event-free survival was 33.9
      months, and 90.5% of patients were alive. Grade 3 or 4 severe infections occurred
      in 7.7% of patients. Grade 3 or 4 adverse events for neutropenia,
      thrombocytopenia, and anemia were documented in 19.7%, 22.2%, and 19.7% of
      patients, respectively. CONCLUSION: Chemoimmunotherapy with BR is effective and
      safe in patients with previously untreated CLL.

PMID- 22869885
TI  - Randomized phase II trial designs with biomarkers.
AB  - Efficient development of targeted therapies that may only benefit a fraction of
      patients requires clinical trial designs that use biomarkers to identify
      sensitive subpopulations. Various randomized phase III trial designs have been
      proposed for definitive evaluation of new targeted treatments and their
      associated biomarkers (eg, enrichment designs and biomarker-stratified designs).
      Before proceeding to phase III, randomized phase II trials are often used to
      decide whether the new therapy warrants phase III testing. In the presence of a
      putative biomarker, the phase II trial should also provide information as to what
      type of biomarker phase III trial is appropriate. A randomized phase II biomarker
      trial design is proposed, which, after completion, recommends the type of phase
      III trial to be used for the definitive testing of the therapy and the biomarker.
      The recommendations include the possibility of proceeding to a randomized phase
      III of the new therapy with or without using the biomarker and also the
      possibility of not testing the new therapy further. Evaluations of the proposed
      trial design using simulations and published data demonstrate that it works well
      in providing recommendations for phase III trial design.

PMID- 22869886
TI  - Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage
      colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with
      stage 4 neuroblastoma in first remission.
AB  - PURPOSE: Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB).
      Prognostic variables that could influence clinical outcome were explored.
      PATIENTS AND METHODS: One hundred sixty-nine children diagnosed with stage 4 NB
      (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 +/- GM-CSF
      +/- 13-cis-retinoic acid (CRA) protocols after achieving first remission
      (complete remission/very good partial remission). Patients enrolled in regimen A
      (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR
      patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT);
      and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT,
      whereas 28 of 85 required additional induction therapy and were deemed ultra high
      risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative
      reverse transcription polymerase chain reaction. Survival probability was
      calculated by the Kaplan-Meier method, and prognostic variables were analyzed by
      multivariate Cox regression model. RESULTS: At 5 years from the start of
      immunotherapy, progression-free survival (PFS) improved from 44% for HR patients
      receiving regimen A to 56% and 62% for those receiving regimens B and C,
      respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and
      OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated
      sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle
      two MRD (PFS and OS), whereas the prognostic factors for improved outcome were
      missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse
      antibody response (OS), and regimen C (OS). CONCLUSION: Retrospective analysis of
      consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA
      is effective against chemotherapy-resistant marrow MRD. Its positive impact on
      long-term survival can only be confirmed definitively by randomized studies.

PMID- 22869887
TI  - International Prognostic Score in advanced-stage Hodgkin's lymphoma: altered
      utility in the modern era.
AB  - PURPOSE: The International Prognostic Score (IPS) is the most widely used risk
      stratification index for Hodgkin's lymphoma (HL). It is based on patients treated
      before 1992 and predicts 5-year freedom from progression (FFP) and overall
      survival (OS) ranging from 42% to 84% and 56% to 89%, respectively. The IPS has
      not been validated in a recently treated population in which outcomes have
      improved compared with historic results. PATIENTS AND METHODS: By using the
      British Columbia Cancer Agency Lymphoid Cancer Database, we identified all
      patients age >= 16 years newly diagnosed with advanced-stage HL (stage III to IV,
      or stage I to II with "B" symptoms or bulky disease >= 10 cm) from 1980 to 2010,
      treated with curative intent with doxorubicin, bleomycin, vinblastine, and
      dacarbazine (ABVD) or an ABVD-equivalent regimen with complete clinical
      information. RESULTS: In all, 740 patients were identified. Five-year FFP and OS
      were 78% and 90%, respectively. The IPS was prognostic for both FFP (P < .001)
      and OS (P < .001), with 5-year FFP ranging from 62% to 88% and 5-year OS ranging
      from 67% to 98%. Analysis limited to patients age 16 to 65 years (n = 686)
      demonstrated a narrower range of outcomes, with 5-year FFP ranging from 70% to
      88% and 5-year OS ranging from 73% to 98%. CONCLUSION: The IPS remains prognostic
      for advanced-stage HL, but the range of outcomes has narrowed considerably. This
      improvement in outcome with ABVD should be acknowledged before consideration of
      alternate initial therapies and when comparing results from current trials with
      those of historic controls.

PMID- 22869888
TI  - Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for
      patients presenting with surgically unresectable metastatic colon cancer and an
      intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10.
AB  - PURPOSE: Major concerns surround combining chemotherapy with bevacizumab in
      patients with colon cancer presenting with an asymptomatic intact primary tumor
      (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of
      asymptomatic IPT is controversial. PATIENTS AND METHODS: Eligibility for this
      prospective, multicenter phase II trial included Eastern Cooperative Oncology
      Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable
      metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin
      (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity
      events, defined as surgical resection because of symptoms at or death related to
      the IPT. A 25% major morbidity rate was considered acceptable. Secondary end
      points included overall survival (OS) and minor morbidity related to IPT
      requiring hospitalization, transfusion, or nonsurgical intervention. RESULTS:
      Ninety patients registered between March 2006 and June 2009: 86 were eligible
      with follow-up, median age was 58 years, and 52% were female. Median follow-up
      was 20.7 months. There were 12 patients (14%) with major morbidity related to
      IPT: 10 required surgery (eight, obstruction; one, perforation; and one,
      abdominal pain), and two patients died. The 24-month cumulative incidence of
      major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected
      without a morbidity event: eight for attempted cure and three for other reasons.
      Two patients had minor morbidity events only: one hospitalization and one
      nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2
      months). CONCLUSION: This trial met its primary end point. Combining mFOLFOX6
      with bevacizumab did not result in an unacceptable rate of obstruction,
      perforation, bleeding, or death related to IPT. Survival was not compromised.
      These patients can be spared initial noncurative resection of their asymptomatic
      IPT.

PMID- 22869889
TI  - Pathologic complete response of a malignant peripheral nerve sheath tumor in the
      lung treated with neoadjuvant Ifosfamide and radiation therapy.

PMID- 22869891
TI  - Aggressive leptomeningeal gliomatosis in neurofibromatosis type 1.

PMID- 22869890
TI  - Factors associated with receipt of breast cancer adjuvant chemotherapy in a
      diverse population-based sample.
AB  - PURPOSE: Disparities in receipt of adjuvant chemotherapy may contribute to higher
      breast cancer fatality rates among black and Hispanic women compared with non
      Hispanic whites. We investigated factors associated with receipt of chemotherapy
      in a diverse population-based sample. PATIENTS AND METHODS: Women diagnosed with
      breast cancer between August 2005 and May 2007 (N = 3,252) and reported to the
      Detroit, Michigan, or Los Angeles County Surveillance, Epidemiology, and End
      Results (SEER) registry were recruited to complete a survey. Multivariable
      analyses examined factors associated with chemotherapy receipt. RESULTS: The
      survey was sent to 3,133 patients; 2,290 completed a survey (73.1%), and 1,403 of
      these patients were included in the analytic sample. In multivariable models,
      disease characteristics were significantly associated with the likelihood of
      receiving chemotherapy. Low-acculturated Hispanics were more likely to receive
      chemotherapy than non-Hispanic whites (odds ratio [OR], 2.00; 95% CI, 1.31 to
      3.04), as were high-acculturated Hispanics (OR, 1.43; 95% CI, 1.03 to 1.98).
      Black women were less likely to receive chemotherapy than non-Hispanic whites,
      but the difference was not significant (OR, 0.83; 95% CI, 0.64 to 1.08).
      Increasing age (even in women age < 50 years) and Medicaid insurance were
      associated with lower rates of chemotherapy receipt. CONCLUSION: In this
      population-based sample, disease characteristics were strongly associated with
      receipt of chemotherapy, indicating that clinical benefit guides most treatment
      decisions. We found no compelling evidence that black women and Hispanics receive
      chemotherapy at lower rates. Interventions that address chemotherapy use rates
      according to age and insurance status may improve quality of systemic treatment.

PMID- 22869892
TI  - A role for apoptosis-inducing factor in T cell development.
AB  - Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates
      cell metabolism and survival in many tissues. We report that aif-hypomorphic
      harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte
      developmental block associated with apoptosis at the beta-selection stage,
      independent of T cell receptor beta recombination. No abnormalities are observed
      in the B cell lineage. Transgenes encoding wild-type or DNA-binding-deficient
      mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase
      activity-deficient mutant Aif does not. The Hq thymic block is reversed in vivo
      by antioxidant treatment, and Hq T but not B lineage cells show enhanced
      oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific
      nonredundant antiapoptotic role in the T cell lineage by regulating reactive
      oxygen species during thymic beta-selection.

PMID- 22869893
TI  - Mutually exclusive redox forms of HMGB1 promote cell recruitment or
      proinflammatory cytokine release.
AB  - Tissue damage causes inflammation, by recruiting leukocytes and activating them
      to release proinflammatory mediators. We show that high-mobility group box 1
      protein (HMGB1) orchestrates both processes by switching among mutually exclusive
      redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide
      bond makes it a proinflammatory cytokine and further cysteine oxidation to
      sulfonates by reactive oxygen species abrogates both activities. We show that
      leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1
      mutant in which serines replace all cysteines (3S-HMGB1) does not promote
      cytokine production, but is more effective than wild-type HMGB1 in recruiting
      leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte
      recruitment but not with activation. We detected the different redox forms of
      HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and
      disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile
      inflammation, leukocyte recruitment and their induction to secrete inflammatory
      cytokines, by adopting mutually exclusive redox states.

PMID- 22869894
TI  - Final report of the Cosmetic Ingredient Review Expert Panel on the safety
      assessment of methyl acetate.
AB  - Alkyl acetates, as well as acetic acid and acetate salts, are widely used
      cosmetic ingredients, with a wide range of functions as fragrances, solvents, or
      skin-conditioning agents, depending on the specific ingredient. Available data on
      alkyl acetates, and acetic acid and the alcohol to which they could be
      metabolized, were considered adequate to support the safety of the entire group
      in the present practices of use and concentration in cosmetics.

PMID- 22869895
TI  - Final report of the Cosmetic Ingredient Review Expert Panel on the safety
      assessment of dicarboxylic acids, salts, and esters.
AB  - The CIR Expert Panel assessed the safety of dicarboxylic acids and their salts
      and esters as used in cosmetics. Most dicarboxylic acids function in cosmetics as
      pH adjusters or fragrance ingredients, but the functions of most of the salts in
      cosmetics are not reported. Some of the esters function as skin conditioning or
      fragrance ingredients, plasticizers, solvents, or emollients. The Expert Panel
      noted gaps in the available safety data for some of the dicarboxylic acid and
      their salts and esters in this safety assessment. The available data on many of
      the ingredients are sufficient, however, and similar structural activity
      relationships, biologic functions, and cosmetic product usage suggest that the
      available data may be extrapolated to support the safety of the entire group. The
      Panel concluded that the ingredients named in this report are safe in the present
      practices of use and concentration.

PMID- 22869896
TI  - Final report of the Cosmetic Ingredient Review Expert Panel on the safety
      assessment of cocamidopropyl betaine (CAPB).
AB  - Cocamidopropyl betaine (CAPB) and related amidopropyl betaines are zwitterions
      used mainly as surfactants in cosmetics. These cosmetic ingredients are similar
      in their chemistry, in particular with respect to the presence of 3,3
      dimethylamino-propylamine (DMAPA) and fatty acid amidopropyl dimethylamine
      (amidoamine) impurities, which are known as sensitizers. The CIR Expert Panel
      concluded that because these ingredients present no other significant toxicity,
      when formulated to be nonsensitizing (which may be based on a quantitative risk
      assessment), these ingredients are safe for use as cosmetic ingredients in the
      practices of use and concentration of this safety assessment.

PMID- 22869897
TI  - Satisfaction with care: the role of patient-provider racial/ethnic concordance
      and interpersonal sensitivity.
AB  - OBJECTIVE: This study examined how patients' satisfaction with their care is
      affected by racial/ethnic concordance and patients' perceived interpersonal
      sensitivity of their providers. The sample consisted of non-Hispanic Whites,
      African Americans/Blacks, Hispanics/Latinos, and Asian Americans age 50 and
      older. METHOD: Data came from the population-based Commonwealth Fund 2001 Health
      Care Quality Survey (n=2,075). A hierarchical regression model of satisfaction
      was estimated for each racial/ethnic group with a sequential entry of variables:
      demographic and health-related variables, racial/ethnic concordance between
      patient and provider, and interpersonal sensitivity. RESULTS: The influence of
      patient-provider racial/ethnic concordance on satisfaction with care was
      negligible, but the influence of interpersonal sensitivity was substantial
      (p<.001) in all racial/ethnic groups. DISCUSSION: Findings suggest that
      racial/ethnic concordance may not be universally effective for diverse older
      populations, but perceived interpersonal sensitivity of the provider has a strong
      influence on older adults' satisfaction with care regardless of their
      racial/ethnic background.

PMID- 22869898
TI  - Depression and self-reported disability among older people in Western Europe.
AB  - OBJECTIVE: To analyze the existing levels of depression among older people (aged
      50 or older) with and without disabilities at a European level. METHODS: We
      analyse and compare the levels of depression among people with and without
      disabilities in 11 Western European countries through the use of the indicator
      EURO-D. We employ a logistic model for each country to estimate the effects of
      self-reported disability on the likelihood of being depressed. RESULTS: Older
      people with disabilities suffer higher levels of depression as compared with
      their nondisabled counterparts, especially among women. Furthermore, significant
      regional differences in the levels of depression are found. DISCUSSION: The high
      prevalence of depression among disabled older individuals is a phenomenon of
      especial interest and medical, social, and economic relevance within Europe and
      has important effects on the levels of well-being, employment and income reported
      by all older people in general, and disabled older people in particular.

PMID- 22869899
TI  - Impact of social capital on 8-year mortality among older people in 34 Danish
      municipalities.
AB  - OBJECTIVE: To analyze the impact of social capital measures (bonding, bridging,
      and linking) on all-cause mortality at 8-year follow-up among older people aged
      75 and 80 at baseline. METHOD: Prospective cohort study on preventive home visits
      including 2,863 seventy-five-year-olds and 1,171 eighty-year-olds in 34 Danish
      municipalities. The associations of the three aspects of social capital measures
      with mortality were tested in Cox regression models on time to death. RESULTS: In
      the 80-year-old cohort significant associations were seen between mortality and
      both bridging (hazards ratio (HR)=1.24, 95% CI [1.07, 1.45]) and linking
      (HR=1.21, 95% CI [1.03, 1.43]), but the associations attenuated when controlling
      for relevant confounders. None of the social capital measures were associated
      with mortality among the 75-year-olds. CONCLUSION: The measures of social capital
      used in the present study include key aspects of social capital that are
      associated to mortality in older populations via physical activity and mobility
      disability.

PMID- 22869900
TI  - Elders' preferences for life-prolonging treatment and their proxies' substituted
      judgment: influence of the elders' current health.
AB  - OBJECTIVE: People in poor health tend to view life-prolonging treatments (e.g.,
      tube feeding) as more acceptable than do healthier people. Do proxies'
      substituted judgments reveal a similar tendency, showing greater acceptance when
      the elder is in worse health? METHOD: In a cross-sectional telephone-based survey
      of 202 elderly individuals and their proxies, preferences for 4 life-prolonging
      treatments in 7 health prospects were examined in relation to the elder's current
      health status, operationalized as number of deficits in activities of daily
      living. RESULTS: Stronger preferences for life-prolonging treatments in worse
      health prospects were expressed by both elders and proxies when the elders'
      current health was relatively poor. The interaction effect was at least as
      pronounced for proxies' substituted judgment as for elders' own preferences.
      DISCUSSION: Findings provide important insight into proxy decision making and
      have particular implications for proxy decision making on behalf of elders with
      dementia or other causes of decisional incapacity.

PMID- 22869901
TI  - Dietary folic acid promotes survival of Foxp3+ regulatory T cells in the colon.
AB  - Dietary compounds as well as commensal microbiota contribute to the generation of
      a unique gut environment. In this study, we report that dietary folic acid (FA)
      is required for the maintenance of Foxp3+ regulatory T cells (Tregs) in the
      colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3+ Tregs
      selectively in the colon. Blockade of folate receptor 4 and treatment with
      methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3+
      Tregs. Compared with splenic Tregs, colonic Tregs were more activated to
      proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs
      derived from mice fed with a FA-deficient diet, expression of anti-apoptotic
      molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of
      peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further
      decrease by additional FA deficiency was observed exclusively in the colon. Mice
      fed with an FA-deficient diet exhibited higher susceptibility to intestinal
      inflammation. These findings reveal the previously unappreciated role of dietary
      FA in promotion of survival of Foxp3+ Tregs that are in a highly activated state
      in the colon.

PMID- 22869902
TI  - IL-10 acts as a developmental switch guiding monocyte differentiation to
      macrophages during a murine peritoneal infection.
AB  - The peritoneal wash of BALB/c or C57BL/6 mice contains two populations of
      macrophages that differ in their level of expression of MHC class II (MHC II).
      Although both populations efficiently phagocytose bacteria in vivo, only the MHC
      II(lo) population is effective at phagocytosing apoptotic cells in vivo and only
      the MHC II(hi) population is effective at presenting Ag to T cells in vitro. Soon
      after induction of a peritoneal infection both of these macrophage populations
      are lost from the peritoneal wash fraction. Blood monocytes then enter the
      inflamed peritoneum and develop into new peritoneal macrophages. Whether these
      monocytes develop into MHC II(lo) or into MHC II(hi) macrophages is crucially
      dependent on the cytokine IL-10, which is transiently elevated in the peritoneal
      wash during the early phase of infection. Monocytes from CD45.1 animals
      transferred early in infection when the IL-10 concentration is high into congenic
      CD45.2 recipients develop into the MHC II(lo) macrophage population. Monocytes
      transferred later, when the IL-10 concentration has fallen, develop into the MHC
      II(hi) population. In infected IL-10-deficient animals monocytes fail to develop
      into the MHC II(lo) population but can be induced to do so by exogenous
      application of IL-10. Finally, high numbers of wild-type monocytes injected into
      IL-10R1-deficient animals develop into MHC II(lo) macrophages and were able by a
      bystander effect to induce the differentiation of the endogenous monocytes to the
      same fate.

PMID- 22869903
TI  - IFN-gamma production by allogeneic Foxp3+ regulatory T cells is essential for
      preventing experimental graft-versus-host disease.
AB  - It is emerging that CD4+Foxp3+ regulatory T (Treg) cells can produce the
      proinflammatory cytokine IFN-gamma when stimulated in a Th1 cytokine environment.
      In this study, we report that Foxp3+ Treg cells readily produced IFN-gamma in
      vivo in a highly inflammatory model of graft-versus-host disease (GVHD) and
      during a Th1-dominated immune response to intracellular bacteria. Moreover,
      stimulation in vitro via TCR in the presence of IL-12 alone was sufficient to
      induce IFN-gamma production by Treg cells in a dose-dependent manner. Transfer of
      donor Treg cells can prevent lethal GVHD; therefore, we used this model as a
      robust readout for in vivo Treg function. Interestingly, >50% of allogeneic
      donor, but not residual recipient Foxp3+ Treg cells produced IFN-gamma after
      transplantation, suggesting that this cytokine production was alloantigen
      specific. These IFN-gamma producers were stable Foxp3+ Treg cells because
      methylation analysis of the Foxp3 gene locus of transferred and reisolated Treg
      cells during GVHD showed a fully demethylated Treg-specific-demethylated region.
      Next, we addressed whether IFN-gamma production was supporting or rather
      impairing the immunosuppressive function of Treg cells during GVHD. Blocking of
      IFN-gamma with specific mAb completely abolished the beneficial effect of donor
      Treg cells. We could further show that only wild-type Treg cells, but not Treg
      cells from IFN-gamma-deficient donor mice, prevented GVHD. This indicated that
      Treg cell-intrinsic IFN-gamma production was required for their protective
      function. In conclusion, our data show that IFN-gamma produced by Foxp3+ Treg
      cells has essential immune-regulatory functions that are required for prevention
      of experimental GVHD.

PMID- 22869905
TI  - Role of Mincle in alveolar macrophage-dependent innate immunity against
      mycobacterial infections in mice.
AB  - The role of macrophage-inducible C-type lectin Mincle in lung innate immunity
      against mycobacterial infection is incompletely defined. In this study, we show
      that wild-type (WT) mice responded with a delayed Mincle induction on resident
      alveolar macrophages and newly immigrating exudate macrophages to infection with
      Mycobacterium bovis bacillus Calmette-Guerin (BCG), peaking by days 14-21
      posttreatment. As compared with WT mice, Mincle knockout (KO) mice exhibited
      decreased proinflammatory mediator responses and leukocyte recruitment upon M.
      bovis BCG challenge, and they demonstrated increased mycobacterial loads in
      pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on
      day 14 after primary BCG challenge led to increased cytokine gene expression in
      sorted alveolar macrophages of WT mice, but not Mincle KO mice, resulting in
      substantially reduced alveolar neutrophil recruitment and increased mycobacterial
      loads in the lungs of Mincle KO mice. Collectively, these data show that WT mice
      respond with a relatively late Mincle expression on lung sentinel cells to M.
      bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin
      Mincle on professional phagocytes critically shapes antimycobacterial responses
      in both pulmonary and extrapulmonary organ systems of mice, which may be
      important for elucidating the role of Mincle in the control of mycobacterial
      dissemination in mice.

PMID- 22869904
TI  - The chemokine receptors CXCR1 and CXCR2 couple to distinct G protein-coupled
      receptor kinases to mediate and regulate leukocyte functions.
AB  - The chemokine receptors, CXCR1 and CXCR2, couple to Galphai to induce leukocyte
      recruitment and activation at sites of inflammation. Upon activation by CXCL8,
      these receptors become phosphorylated, desensitized, and internalized. In this
      study, we investigated the role of different G protein-coupled receptor kinases
      (GRKs) in CXCR1- and CXCR2-mediated cellular functions. To that end, short
      hairpin RNA was used to inhibit GRK2, 3, 5, and 6 in RBL-2H3 cells stably
      expressing CXCR1 or CXCR2, and CXCL8-mediated receptor activation and regulation
      were assessed. Inhibition of GRK2 and GRK6 increased CXCR1 and CXCR2 resistance
      to phosphorylation, desensitization, and internalization, respectively, and
      enhanced CXCL8-induced phosphoinositide hydrolysis and exocytosis in vitro. GRK2
      depletion diminished CXCR1-induced ERK1/2 phosphorylation but had no effect on
      CXCR2-induced ERK1/2 phosphorylation. GRK6 depletion had no significant effect on
      CXCR1 function. However, peritoneal neutrophils from mice deficient in GRK6
      (GRK6(-/-)) displayed an increase in CXCR2-mediated G protein activation but in
      vitro exhibited a decrease in chemotaxis, receptor desensitization, and
      internalization relative to wild-type (GRK6(+/+)) cells. In contrast, neutrophil
      recruitment in vivo in GRK6(-/-) mice was increased in response to delivery of
      CXCL1 through the air pouch model. In a wound-closure assay, GRK6(-/-) mice
      showed enhanced myeloperoxidase activity, suggesting enhanced neutrophil
      recruitment, and faster wound closure compared with GRK6(+/+) animals. Taken
      together, the results indicate that CXCR1 and CXCR2 couple to distinct GRK
      isoforms to mediate and regulate inflammatory responses. CXCR1 predominantly
      couples to GRK2, whereas CXCR2 interacts with GRK6 to negatively regulate
      receptor sensitization and trafficking, thus affecting cell signaling and
      angiogenesis.

PMID- 22869906
TI  - NK cells regulate CD8+ T cell priming and dendritic cell migration during
      influenza A infection by IFN-gamma and perforin-dependent mechanisms.
AB  - An effective immune response against influenza A infection depends on the
      generation of virus-specific T cells. NK cells are one of the first-line defenses
      against influenza A infection. We set out to delineate the role of NK cells in T
      cell immunity using a murine model of influenza A infection with A/PR/8/34. We
      show that early T cell recruitment mainly occurs in the posterior mediastinal
      lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic
      cell (DC) and T cell recruitment into the pMLN. A similar reduction of T cell
      recruitment was observed when migration was blocked by pertussis toxin,
      suggesting that migration of pulmonary NK cells and DCs regulates cell
      recruitment to the pMLN. T cell recruitment was dependent on IFN-gamma, and
      transfer of IFN-gamma-competent naive NK cells into IFN-gamma-/- mice restored T
      cell recruitment, whereas IFN-gamma-deficient NK cells failed to do so. In
      addition, NK cell depletion reduced the uptake and transport of influenza A virus
      by DCs, and significantly impaired the virus-specific T cell response. Both IFN
      gamma-/- and perforin-/- mice showed reduced viral Ag transport by DCs,
      suggesting that the ability of NK cells to influence virus transport depends on
      IFN-gamma and perforin. In summary, our data suggest that NK cells play a
      critical role in the initiation and shaping of the T cell response after
      influenza A infection.

PMID- 22869908
TI  - Ulnar nerve transposition using a mini-invasive approach: case series of 30
      patients.
AB  - The treatment of ulnar nerve compression at the elbow remains controversial. No
      single technique has yet proven its superiority. We describe a technique
      combining the advantages of the mini-invasive approach with those of
      transposition. We present the results of 30 patients, of mean age 52 years, who
      underwent anterior subcutaneous transposition of the ulnar nerve using a mini
      invasive approach with a follow-up of more than six months. The incision measures
      3 cm. The results were evaluated by measuring pain intensity, quick disabilities
      of the arm shoulder and hand (DASH), grip strength and pinch, and McGowan score,
      pre- and post-operatively. All parameters were improved post-operative. The mean
      pain score went from 5.5 to 4, the quick DASH from 48 to 38, mean grip strength
      from 28 to 31 kg, and mean pinch strength from 4.7 to 6.4 kg. The McGowan score
      was also improved; pre-operatively, there were 16 patients at stage III, seven
      patients stage II, seven patients stage I, and post-operatively there was one
      patient stage III, three patients stage II, 16 patients stage I, and 10 patients
      stage 0. Analysis of our series shows that a 3 cm incision without endoscopy
      allows subcutanous transposition, with results at least as good as those with
      other techniques. The advantages of our technique are that it is easy, has a
      limited approach, preserves blood supply, allows placement of the nerve in a
      favourable environment, and decreases nerve stretching during elbow flexion.

PMID- 22869907
TI  - Stabilization of HIF-2alpha induces sVEGFR-1 production from tumor-associated
      macrophages and decreases tumor growth in a murine melanoma model.
AB  - Macrophage secretion of vascular endothelial growth factor (VEGF) in response to
      hypoxia contributes to tumor growth and angiogenesis. In addition to VEGF,
      hypoxic macrophages stimulated with GM-CSF secrete high levels of a soluble form
      of the VEGF receptor (sVEGFR-1), which neutralizes VEGF and inhibits its
      biological activity. Using mice with a monocyte/macrophage-selective deletion of
      hypoxia-inducible factor (HIF)-1alpha or HIF-2alpha, we recently demonstrated
      that the antitumor response to GM-CSF was dependent on HIF-2alpha-driven sVEGFR-1
      production by tumor-associated macrophages, whereas HIF-1alpha specifically
      regulated VEGF production. We therefore hypothesized that chemical stabilization
      of HIF-2alpha using an inhibitor of prolyl hydroxylase domain 3 (an upstream
      inhibitor of HIF-2alpha activation) would increase sVEGFR-1 production from GM
      CSF-stimulated macrophages. Treatment of macrophages with the prolyl hydroxylase
      domain 3 inhibitor AKB-6899 stabilized HIF-2alpha and increased sVEGFR-1
      production from GM-CSF-treated macrophages, with no effect on HIF-1alpha
      accumulation or VEGF production. Treatment of B16F10 melanoma-bearing mice with
      GM-CSF and AKB-6899 significantly reduced tumor growth compared with either drug
      alone. Increased levels of sVEGFR-1 mRNA, but not VEGF mRNA, were detected within
      the tumors of GM-CSF- and AKB-6899-treated mice, correlating with decreased tumor
      vascularity. Finally, the antitumor and antiangiogenic effects of AKB-6899 were
      abrogated when mice were simultaneously treated with a sVEGFR-1 neutralizing Ab.
      These results demonstrate that AKB-6899 decreases tumor growth and angiogenesis
      in response to GM-CSF by increasing sVEGFR-1 production from tumor-associated
      macrophages. Specific activation of HIF-2alpha can therefore decrease tumor
      growth and angiogenesis.

PMID- 22869909
TI  - Evaluation of pharmacist continuing professional development portfolios.
AB  - OBJECTIVE: The purpose of this study was to conduct a random continuing
      professional development (CPD) portfolio audit to assess the portfolios of
      pharmacists who completed CPD training in the state of North Carolina and
      reported adopting it in place of the annual 15-hour continuing education (CE)
      requirement when applying for re-licensure. METHODS: The NC Board of Pharmacy
      (NCBOP) staff randomly selected 30 pharmacists to provide CPD portfolio
      documentation to the Board electronically or in paper format. This documentation
      included their completed learning plan, a learning activity worksheet for each
      completed activity, and the Accreditation Council on Pharmacy Education (ACPE)
      universal activity number for the CPD training program attended. The Task Force
      used a multicomponent audit tool to assess each portfolio. RESULTS: Eighty
      percent of portfolios had at least 15 hours of learning reported. Portfolio
      assessments indicated an average of 5 learning objectives per individual. Based
      on the scale of 1 to 5, the Measurable and Specific sections of the objectives
      scored the lowest with an average score of 3 on both sections. An overall
      assessment of "adequate" or "comprehensive" was noted for 60% of the portfolios.
      CONCLUSION: Pharmacists completing CPD training are capable of following the CPD
      process with some potential challenges in documentation. Information submitted to
      the board of pharmacy is considered sufficient for license renewal purposes.

PMID- 22869910
TI  - Bovine hemoglobin: a nontraditional approach to the management of acute anemia in
      a Jehovah's Witness patient with autoimmune hemolytic anemia.
AB  - INTRODUCTION: Management of severe symptomatic anemia in critically ill Jehovah's
      Witness patients remains a challenge. The paucity of therapeutic alternatives to
      human red blood cells has prompted the use of blood substitutes. CASE REPORT: A
      19-year-old female Jehovah's Witness patient presented to the emergency
      department following several episodes of syncope. She was found to have a
      positive Coombs test and was diagnosed with warm-bodied autoimmune hemolytic
      anemia. Upon admission, her hemoglobin was 8.4 g/dL, then dropped to a nadir of
      2.8 g/dL 4 days later. She received traditional management with corticosteroids,
      intravenous immune globulin, rituximab, and partial splenic artery embolization.
      Despite these therapies, hemoglobin levels failed to respond, and she experienced
      signs of marked ischemia. A decision was made to give 2 units of Hemopure, a
      bovine hemoglobin-based oxygen carrier, and the hemoglobin levels increased to
      8.7 g/dL 10 days later. The patient's overall clinical condition improved leading
      to subsequent hospital discharge. CONCLUSION: This case exemplifies the ingenuity
      that health care practitioners must use in critical situations involving the
      medical management of anemic Jehovah's Witness patients who refuse blood
      products. Hemopure was used as "bridging treatment" to help save a patient from
      the devastating effects of ischemia resulting from severe anemia.

PMID- 22869911
TI  - Significance of isolated reactive treponemal chemiluminescence immunoassay
      results.
AB  - BACKGROUND: Isolated reactive serum treponemal chemiluminescence immunoassay
      (CIA) specimens cause clinical uncertainty. METHODS: Sera were screened by CIA,
      and reactive samples underwent reflex testing with rapid plasma reagin (RPR),
      Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal
      antibody absorption (FTA Abs) assays. Samples reactive only on the CIA were
      deemed "isolated" reactive CIA samples. We undertook detailed review of a subset
      of subjects with isolated reactive CIA specimens. RESULTS: Of 28 261 specimens,
      1171 (4.1%) were reactive on CIA, of which 133 (11.3%) had isolated CIA
      reactivity. Most subjects (66 of 82 [80.5%]) with isolated reactive CIA specimens
      were from high-prevalence populations. We found evidence of CIA, TPPA, and FTA
      Abs seroreversion. The median chemiluminescent signal-to-cutoff ratio was similar
      for isolated reactive CIA sera and sera that were reactive on either FTA Abs or
      TPPA assays (2.19 vs 2.32; P = .15) but lower than for sera reactive on both FTA
      Abs and TPPA assays (12.37; P < .001) or for sera reactive on RPR assays (25.53;
      P < .001). A total of 11 of 20 patients (55%) with an isolated reactive CIA
      specimen who underwent medical record review had previous or subsequent evidence
      of syphilis infection. CONCLUSIONS: Isolated reactive CIA specimens may represent
      true T. pallidum infection and may be found after seroreversion of traditional
      treponemal assays.

PMID- 22869912
TI  - Hantaan virus RNA load in patients having hemorrhagic fever with renal syndrome:
      correlation with disease severity.
AB  - To investigate the role of viral load in the pathogenesis of hemorrhagic fever
      with renal syndrome, the Hantaan virus RNA load in plasma from 101 patients was
      quantified, and the relationships between viral load and disease course,
      severity, and level of specific humoral immunity were analyzed. The viral load,
      detectable in 79 patients, ranged from 3.43 to 7.33 log10 copies/mL of plasma. In
      the early stage of disease, patients in severe/critical group were found to have
      higher viral loads than those in the mild/moderate group (5.90 vs 5.03 log10
      copies/mL; P = .001), suggesting an association between Hantaan virus load and
      disease severity.

PMID- 22869913
TI  - Time perspective and physical activity among central Appalachian adolescents.
AB  - Time perspective is a cultural behavioral concept that reflects individuals'
      orientations or attitudes toward the past, present, or future. Individuals' time
      perspectives influence their choices regarding daily activities. Time perspective
      is an important consideration when teaching adolescents about the importance of
      being physically active. However, little is known about the relationship between
      time perspective and physical activity among adolescents. The purpose of this
      study was to determine the time perspective of central Appalachian adolescents
      and explore the relationship between time perspective and physical activity. This
      study was guided by The theory of planned behavior (TPB). One hundred and ninety
      three students completed surveys to examine time perspective and physical
      activity behaviors. Data were collected in one school. Results of this study can
      inform school nurses and high school guidance counselors about the importance of
      promoting a future-oriented time perspective to improve physical activity and
      educational outcomes.

PMID- 22869919
TI  - Why do some patients after head injury deteriorate over the long term?

PMID- 22869920
TI  - Biomarkers for dementia diagnosis: differentiating DLB and FTD may be difficult.

PMID- 22869921
TI  - Differentiation of frontotemporal dementia from dementia with Lewy bodies using
      FP-CIT SPECT.
AB  - INTRODUCTION: There is increasing evidence that imaging with [123I]FP-CIT SPECT
      is helpful in differentiating dementia with Lewy bodies (DLB) from Alzheimer's
      disease (AD) but it is not known how well the scan performs in differentiating
      DLB from frontotemporal dementia (FTD). METHOD: We compared the striatal dopamine
      transporter (DAT) binding in FTD (n=12), DLB (n=10) and AD (n=9) by visually
      rating the caudate and putamen on [123I]FP-CIT SPECT scans. RESULTS: The majority
      (9/10) of DLB cases had an abnormal scan and a significant reduction of uptake of
      DAT binding in the putamen and the caudate. A third (4/12) of the FTD cases also
      had an abnormal scan and a significant reduction in uptake in the putamen and the
      caudate. In contrast, only one out of nine AD cases had an abnormal scan.
      Significant differences were found when comparisons were made between the groups
      for visual analysis of the entire scan (p=0.001) and the four regions of interest
      (p=0.001 - 0.013). In contrast to the AD group (specificity of scan 89%), the
      specificity of [123I]FP-CIT SPECT scans was reduced in the FTD group to 67%.
      Three quarters of the study population had at least one extrapyramidal motor sign
      (EPMS), with bradykinesia being the most common EPMS in both FTD (83%) and DLB
      (70%). CONCLUSIONS: This study highlights to clinicians that a positive
      (abnormal) [123I]FP-CIT SPECT scan, even in a patient with an EPMS, does not
      exclude the diagnosis of FTD and emphasises the importance of a comprehensive
      clinical evaluation and a detailed cognitive assessment.

PMID- 22869922
TI  - Movement kinematic after deep brain stimulation associated microlesions.
AB  - BACKGROUNDS: Deep brain stimulation is widely used for the treatment of movement
      disorders such as Parkinson's disease and dystonia. After the implantation of
      electrodes an immediate improvement of clinical symptoms has been described. It
      is unclear, whether movement kinematics are also changed by this 'microlesion
      effect'. METHODS: To gain further insight into these mechanisms, we studied arm,
      hand and finger movements preoperatively and immediately after the implantation
      of deep brain stimulation electrodes in patients with Parkinson's disease and
      dystonia. RESULTS: After implantation and without stimulation there was a clear
      reduction of clinical symptoms in both groups, as has been described previously.
      However, movement velocity was affected differently. Parkinsonian patients showed
      increased movement velocity postoperatively, whereas dystonic patients were
      significantly slower after electrode implantation. CONCLUSIONS: Lesioning and
      stimulation of these structures have the same beneficial clinical effects.
      Furthermore we suggest that globus pallidus internum lesions act by inhibiting a
      system which mainly acts upon muscular tone and limb posture whereas subthalamic
      stimulation or lesion causes a more unspecific disinhibition of movements.

PMID- 22869923
TI  - Social cognition in neurodegenerative disorders: a systematic review.
AB  - Social cognitive neuroscience is the study of the neurobiological systems
      underlying effective social behaviour. The neural processes supporting effective
      social interactions in everyday life and the consequences of dysfunction in these
      processes have been the focus of intense research over the last two decades. It
      is becoming increasingly apparent that the identification of social cognitive
      deficits in neurodegenerative conditions and their neural basis may provide a
      better understanding of the behavioural changes observed in these disorders. In
      addition, accumulating data suggest that detection of early impairment in social
      cognitive skills may aid in the early diagnosis of cognitive or behavioural
      impairment in some of these disorders, and may even play a role in the
      investigation of new therapeutic options. In this review, we outline the basic
      components of social cognitive processing, provide a systematic review of the
      literature pertaining to common neurodegenerative conditions, discuss current
      controversies and make recommendations for future research.

PMID- 22869924
TI  - Recognition criteria vary with fluctuating uncertainty.
AB  - In distinct experiments we examined memories for orientation and size. After
      viewing a randomly oriented Gabor patch (or a plain white disk of random size),
      observers were given unlimited time to reproduce as faithfully as possible the
      orientation (or size) of that standard stimulus with an adjustable Gabor patch
      (or disk). Then, with this match stimulus still in view, a recognition probe was
      presented. On half the trials, this probe was identical to the standard. We
      expected observers to classify the probe (a same/different task) on the basis of
      its difference from the match, which should have served as an explicit memory of
      the standard. Observers did better than that. Larger differences were classified
      as "same" when probe and standard were indeed identical. In some cases,
      recognition performance exceeded that of a simulated observer subject to the same
      matching errors, but forced to adopt the single most advantageous criterion
      difference between the probe and match. Recognition must have used information
      that was not or could not be exploited in the reproduction phase. One possible
      source for that information is observers' confidence in their reproduction (e.g.,
      in their memory of the standard). Simulations confirm the enhancement of
      recognition performance when decision criteria are adjusted trial-by-trial, on
      the basis of the observer's estimated reproduction error.

PMID- 22869925
TI  - Effects of ocular aberrations on contrast detection in noise.
AB  - We use adaptive optics (AO) techniques to manipulate the ocular aberrations and
      elucidate the effects of these ocular aberrations on contrast detection in a
      noisy background. The detectability of sine wave gratings at frequencies of 4, 8,
      and 16 circles per degree (cpd) was measured in a standard two-interval force
      choice staircase procedure against backgrounds of various levels of white noise.
      The observer's ocular aberrations were either corrected with AO or left
      uncorrected. In low levels of external noise, contrast detection thresholds are
      always lowered by AO correction, whereas in high levels of external noise, they
      are generally elevated by AO correction. Higher levels of external noise are
      required to make this threshold elevation observable when signal spatial
      frequencies increase from 4 to 16 cpd. The linear-amplifier-model fit shows that
      mostly sampling efficiency and equivalent noise both decrease with AO correction.
      Our findings indicate that ocular aberrations could be beneficial for contrast
      detection in high-level noises. The implications of these findings are discussed.

PMID- 22869926
TI  - Proatherogenic macrophage activities are targeted by the flavonoid quercetin.
AB  - Many studies have demonstrated that the flavonoid quercetin protects against
      cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the
      underlying cause of CVD, is also attenuated by oral quercetin administration in
      animal models. Although macrophages are key players during fatty streak formation
      and plaque progression and aggravation, little is known about the effects of
      quercetin on atherogenic macrophages. Here, we report that primary bone marrow
      derived macrophages internalized less oxidized low-density lipoprotein (oxLDL)
      and accumulated less intracellular cholesterol in the presence of quercetin. This
      reduction of foam cell formation correlated with reduced surface expression of
      the oxLDL receptor CD36. Quercetin also targeted the lipopolysaccharide
      dependent, oxLDL-independent pathway of lipid droplet formation in macrophages.
      In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species
      production and interleukin (IL)-6 secretion. In a system that evaluated
      cholesterol crystal-induced IL-1beta secretion via nucleotide-binding domain and
      leucine-rich repeat containing protein 3 inflammasome activation, quercetin also
      exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-deficient mice
      chronically treated with intraperitoneal quercetin injections had smaller
      atheromatous lesions, reduced lipid deposition, and less macrophage and T cell
      inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum
      levels of total cholesterol and the lipid peroxidation product malondialdehyde
      were also reduced in these mice. Our results demonstrate that quercetin
      interferes with both key proatherogenic activities of macrophages, namely foam
      cell formation and pro-oxidant/proinflammatory responses, and these effects may
      explain the atheroprotective properties of this common flavonoid.

PMID- 22869927
TI  - CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine Delta5'(1')iminium ion.
AB  - Nicotine, the major addictive agent in tobacco, is metabolized primarily by
      CYP2A6-catalyzed oxidation. The product of this reaction, 5'-hydroxynicotine, is
      in equilibrium with the nicotine Delta5'(1')iminium ion and is further
      metabolized to cotinine. We reported previously that both CYP2A6 and the closely
      related extrahepatic enzyme CYP2A13 were inactivated during nicotine metabolism;
      however, inactivation occurred after metabolism was complete. This led to the
      hypothesis that oxidation of a nicotine metabolite, possibly the nicotine
      Delta5'(1')iminium ion, was responsible for generating the inactivating species.
      In the studies presented here, we confirm that the nicotine Delta5'(1')iminium
      ion is an inactivator of both CYP2A6 and CYP2A13, and inactivation depends on
      time, concentration, and the presence of NADPH. Inactivation was not reversible
      and was accompanied by a parallel loss in spectrally active protein, as measured
      by reduced CO spectra. These data are consistent with the characterization of the
      nicotine Delta5'(1')iminium ion as a mechanism-based inactivator of both CYP2A13
      and CYP2A6. We also confirm that both CYP2A6 and CYP2A13 catalyze the metabolism
      of the nicotine Delta5'(1')iminium ion to cotinine and provide evidence that both
      enzymes catalyze the sequential metabolism of the nicotine Delta5'(1')iminium
      ion. That is, a fraction of the cotinine formed may not be released from the
      enzyme before further oxidation to 3'-hydroxycotinine.

PMID- 22869928
TI  - Activation of alternate prosurvival pathways accounts for acquired sunitinib
      resistance in U87MG glioma xenografts.
AB  - Acquired drug resistance represents a major obstacle to using sunitinib for the
      treatment of solid tumors. Here, we examined the cellular and molecular
      alterations in tumors that are associated with acquired brain tumor resistance to
      sunitinib by using an in vivo model. U87MG tumors obtained from nude mice that
      received sunitinib (40 mg/kg/day) for 30 days were classified into sunitinib
      sensitive and -resistant groups based on tumor volume and underwent targeted gene
      microarray and protein array analyses. The expression of several angiogenesis
      associated genes was significantly modulated in sunitinib-treated tumors compared
      with those in control tumors (p<0.05), whereas no significant differences were
      observed between sunitinib-sensitive and -resistant tumors (p>0.05). Tumor
      vasculature based on microvessel density, neurogenin 2 chondroitin sulfate
      proteoglycan density, and alpha-smooth muscle actin density was also similar in
      sunitinib-treatment groups (p>0.05). The moderate increase in unbound sunitinib
      tumor-to-plasma area-under-the-curve ratio in sunitinib-resistant mice was
      accompanied by up-regulated ATP-binding cassette G2 expression in tumor. The most
      profound difference between the sunitinib-sensitive and -resistant groups was
      found in the expression of several phosphorylated proteins involved in
      intracellular signaling. In particular, phospholipase C-gamma1 phosphorylation in
      sunitinib-resistant tumors was up-regulated by 2.6-fold compared with that in
      sunitinib-sensitive tumors (p<0.05). In conclusion, acquired sunitinib resistance
      in U87MG tumors is not associated with revascularization in tumors, but rather
      with the activation of alternate prosurvival pathways involved in an escape
      mechanism facilitating tumor growth and possibly insufficient drug uptake in
      tumor cells caused by an up-regulated membrane efflux transporter.

PMID- 22869929
TI  - Deletion of Abcg2 has differential effects on excretion and pharmacokinetics of
      probe substrates in rats.
AB  - This study was designed to characterize breast cancer resistance protein (Bcrp)
      knockout Abcg2(-/-) rats and assess the effect of ATP-binding cassette subfamily
      G member 2 (Abcg2) deletion on the excretion and pharmacokinetic properties of
      probe substrates. Deletion of the target gene in the Abcg2(-/-) rats was
      confirmed, whereas gene expression was unaffected for most of the other
      transporters and metabolizing enzymes. Biliary excretion of nitrofurantoin,
      sulfasalazine, and compound A [2-(5-methoxy-2-((2-methyl-1,3-benzothiazol-6
      yl)amino)-4-pyridinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one]
      accounted for 1.5, 48, and 48% of the dose in the Abcg2(+/+) rats, respectively,
      whereas it was decreased by 70 to 90% in the Abcg2(-/-) rats. Urinary excretion
      of nitrofurantoin, a significant elimination pathway, was unaffected in the
      Abcg2(-/-) rats, whereas renal clearance of sulfasalazine, a minor elimination
      pathway, was reduced by >90%. Urinary excretion of compound A was minimal.
      Systemic clearance in the Abcg2(-/-) rats decreased 22, 43 (p<0.05), and 57%,
      respectively, for nitrofurantoin, sulfasalazine, and compound A administered at 1
      mg/kg and 27% for compound A administered at 5 mg/kg. Oral absorption of
      nitrofurantoin, a compound with high aqueous solubility and good permeability,
      was not limited by Bcrp. In contrast, the absence of Bcrp led to a 33- and 11
      fold increase in oral exposure of sulfasalazine and compound A, respectively.
      These data show that Bcrp plays a crucial role in biliary excretion of these
      probe substrates and has differential effects on systemic clearance and oral
      absorption in rats depending on clearance mechanisms and compound properties. The
      Abcg2(-/-) rat is a useful model for understanding the role of Bcrp in
      elimination and oral absorption.

PMID- 22869930
TI  - GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent
      Autoimmune Diabetes in Adults (LADA).
AB  - One of the hallmarks of autoimmune diabetes is the presence of adaptive responses
      directed to neuroendocrine proteins. One of these proteins is glutamic acid
      decarboxylase (GAD). While GAD is widely distributed in neuroendocrine tissues,
      its specific significance in diabetes has paralleled the advances in
      understanding humoral and cellular immunity in Type 1 diabetes (T1D) and in a
      subset of Type 2 diabetes (T2D), going from the seminal discoveries of islet
      autoantibodies to the development and standardization of bioassays as diagnostic
      tools, to studies on the structure of GAD and its antigenic determinants. GAD65
      autoantibodies can accurately predict T1D development in combination with other
      surrogate humoral biomarkers and they are considered the most sensitive and
      specific biomarker which identifies a subset of clinically diagnosed T2D termed
      Latent Autoimmune Diabetes in Adults (LADA). We and others provided evidence
      indicating that GAD65 autoantibody detection should be part of the diagnostic
      assessment for clinically diagnosed T2DM mainly because it predicts the rate of
      progression to insulin requirement in patients affected by LADA. More recently
      GAD has been used as a "tolerogenic vaccine" to preserve beta cell function in
      autoimmune diabetes. While the results of Phase III clinical trials did not
      substantiate the earlier promise of Phase I and II trials, there are still many
      unanswered questions and approaches that need to be investigated in the
      applications of GAD in the therapy of T1D and LADA.

PMID- 22869931
TI  - Airway management in neonates and infants with congenital airway lesions.

PMID- 22869932
TI  - Submento-tracheal intubation.

PMID- 22869933
TI  - Submental intubation: A journey over the last 25 years.
AB  - Airway management in patients with faciomaxillary injuries is challenging due to
      disruption of components of upper airway. The anesthesiologist has to share the
      airway with the surgeons. Oral and nasal routes for intubation are often not
      feasible. Most patients have associated nasal fractures, which precludes use of
      nasal route of intubation. Intermittent intraoperative dental occlusion is needed
      to check alignment of the fracture fragments, which contraindicates the use of
      orotracheal intubation. Tracheostomy in such situations is conventional and time
      tested; however, it has life-threatening complications, it needs special
      postoperative care, lengthens hospital stay, and adds to expenses. Retromolar
      intubation may be an option, But the retromolar space may not be adequate in all
      adult patients. Submental intubation provides intraoperative airway control,
      avoids use of oral and nasal route, with minimal complications. Submental
      intubation allows intraoperative dental occlusion and is an acceptable option,
      especially when long-term postoperative ventilation is not planned. This
      technique has minimal complications and has better patients' and surgeons'
      acceptability. There have been several modifications of this technique with an
      expectation of an improved outcome. The limitations are longer time for
      preparation, inability to maintain long-term postoperative ventilation and
      unfamiliarity of the technique itself. The technique is an acceptable alternative
      to tracheostomy for the good per-operative airway access.

PMID- 22869934
TI  - Anesthesia and perioperative management of colorectal surgical patients -
      specific issues (part 2).
AB  - Colorectal surgery carries significant morbidity and mortality, which is
      associated with an enormous use of healthcare resources. Patients with pre
      existing morbidities, and those undergoing emergency colorectal surgery due to
      complications such as perforation, obstruction, or ischemia / infarction are at
      an increased risk for adverse outcomes. Fluid therapy in emergency colorectal
      surgical patients can be challenging as hypovolemic and septic shock may coexist.
      Abdominal sepsis is a serious complication and may be diagnosed during pre-,
      intra-, or postoperative periods. Early suspicion and recognition of medical and
      / or surgical complications are essential. The critical care management of
      complicated colorectal surgical patients require collaborative and
      multidisciplinary efforts.

PMID- 22869936
TI  - A prospective, randomized, Single-blinded, comparative study of Classic Laryngeal
      Mask Airway and ProSeal Laryngeal Mask Airway in pediatric patients.
AB  - CONTEXT: ProSeal Laryngeal Mask Airway (PLMA) is extensively being used in
      pediatric anesthesia. AIMS: To evaluate the efficacy of PLMA as compared to
      Classic Laryngeal Mask Airway (CLMA) for airway maintenance in pediatric
      patients. SETTINGS AND DESIGN: A prospective, randomized, Single-blinded study
      was conducted in a tertiary care teaching hospital. MATERIALS AND METHODS: Sixty
      ASA I and II children were included. Patients were randomized to either size 2
      PLMA or size 2 CLMA groups. Parameters noted were time for insertion, number of
      attempts, airway sealing pressure, blood pressures (systolic, diastolic, and
      mean), pulse rate, end-tidal carbon dioxide (EtCO(2)), peripheral oxygen
      saturation (SpO(2)), and postoperative change in abdominal circumference, and
      airway trauma. STATISTICAL ANALYSIS USED: Parametric data were analyzed with the
      unpaired t-test and non-parametric data were analyzed with the chi-square
      (chi(2)) test. Unless otherwise stated, data are presented as mean (SD).
      Significance was taken as P < 0.05. RESULTS: There was no statistical difference
      between the two groups for the success rates at the first attempt of insertion,
      airway sealing pressure, hemodynamic responses, SpO(2), EtCO(2) and postoperative
      changes in abdominal circumference. Patients in the PLMA group had longer time of
      insertion and higher incidence of airway trauma. CONCLUSIONS: The PLMA and the
      CLMA were comparable for hemodynamic and ventilatory parameters and change in
      abdominal circumference; however, the time taken for insertion and airway trauma
      was more with PLMA.

PMID- 22869935
TI  - Injection pain of propofol in children: A comparison of two formulations without
      added lidocaine.
AB  - BACKGROUND: Propofol emulsion in medium and long-chain triglycerides (MCT/LCT)
      has been reported to cause less injection pain than other propofol solutions in
      adult studies. The aim of this study was to compare the injection pain of two
      different propofol emulsions using two different pain scales on the pediatric
      population. MATERIALS AND METHODS: 100 children scheduled for general anesthesia
      were divided into two groups. Patients were randomly assigned to receive propofol
      LCT or propofol MCT/LCT. Assessment and evaluation of the Ontario Children's
      Hospital Pain Scale (mCHEOPS) and the Wong-Baker Faces Scale (WBFS) were
      performed at the start of the injection until the patients lose consciousness.
      RESULTS: There were no significant differences between groups in terms of
      demographic data. According to the mCHEOPS scale, the pain incidence of propofol
      LCT was 5%, whereas for propofol MCT/LCT it was 15% (P < 0.05). According to the
      WBFS Pain Scale, the pain incidence of propofol LCT was 17%, whereas for propofol
      MCT/LCT it was 21% (P > 0.05). CONCLUSIONS: Propofol MCT/LCT does not decrease
      injection pain; contrary to the general assumption, it causes more pain than
      propofol LCT in children.

PMID- 22869937
TI  - Comparison of Cobra perilaryngeal airway (CobraPLATM) with flexible laryngeal
      mask airway in terms of device stability and ventilation characteristics in
      pediatric ophthalmic surgery.
AB  - BACKGROUND: Supraglottic airway devices play an important role in ophthalmic
      surgery. The flexible laryngeal mask airway (LMATM) is generally the preferred
      airway device. However, there are no studies comparing it with the Cobra
      perilaryngeal airway (CobraPLATM) in pediatric ophthalmic procedures. AIMS: To
      analyze the intraoperative device stability and ability to maintain normocarbia
      of CobraPLATM and compare it to that with flexible LMATM. MATERIALS AND METHODS:
      Ninety children of American Society for Anesthesiologists physical status 1 and
      2, aged 3-15 years scheduled for elective ophthalmic surgeries were randomly
      assigned to either the CobraPLATM or the flexible LMATM group. After placement of
      each airway device, oropharyngeal leak pressure (OLP) was noted. Adequate seal of
      the devices was confirmed at an inspired pressure of 15 cm H(2)O and pressure
      controlled ventilation was initiated. Device displacement was diagnosed if there
      was a change in capnograph waveform, audible or palpable gas leak, change in
      expired tidal volume to <8 ml/kg, end-tidal carbon-dioxide persistently >6 kPa,
      or need to increase inspired pressure to >18 cm H(2)O to maintain normocarbia.
      RESULTS: Demographic data, duration, and type of surgery in both the groups were
      similar. A higher incidence of intraoperative device displacement was noted with
      the CobraPLATM in comparison to flexible LMATM (P < 0.001). Incidence of
      displacement was higher in strabismus surgery (7/12). Insertion characteristics
      and ventilation parameters were comparable. The OLP was significantly higher in
      CobraPLATM group (28 +/- 6.8 cm H(2)O) compared to the flexible LMATM group (19.9
      +/- 4.5 cm H(2)O) (P < 0.001). Higher surgeon dissatisfaction (65.9%) was seen in
      the CobraPLATM group. CONCLUSION: The high incidence of device displacement and
      surgeon dissatisfaction make CobraPLATM a less favorable option than flexible
      LMATM in ophthalmic surgery.

PMID- 22869938
TI  - A randomized comparative study of intraocular pressure and hemodynamic changes on
      insertion of proseal laryngeal mask airway and conventional tracheal intubation
      in pediatric patients.
AB  - OBJECTIVE: To assess the influence of proseal laryngeal mask airway (PLMA)
      insertion on intraocular pressure (IOP). AIM: We compared the effects of PLMA
      insertion and laryngoscopic intubation on IOP and hemodynamic response in
      pediatric patients. BACKGROUND: Previous studies have shown that there is no
      hemodynamic response to PLMA insertion similar to classic LMA insertion, but
      there is no published report about the influence of PLMA insertion on IOP.
      Conventional laryngoscopic tracheal intubation evokes a rise in IOP and
      cardiovascular response and has been traditionally used to secure the airway in
      pediatric patients undergoing ophthalmic surgery. MATERIALS AND METHODS: 59
      patients, less than 14 years of age, scheduled for elective ophthalmic surgery
      were randomly divided into two groups, group P, in which the patient's airway was
      secured with PLMA (using introducer tool technique), and group T, in which the
      airway was secured with laryngoscopy-guided endotracheal intubation. Heart rate,
      blood pressure, and IOP were measured just before insertion of the airway device
      and subsequently three times at intervals of 1 min after insertion of the airway
      device. RESULTS: In group T, there was a significant rise in IOP as well as
      hemodynamic parameters recorded. In group P, there was no significant rise in
      hemodynamic parameters, but a significant rise in IOP was found though the rise
      was less than in group T. CONCLUSION: We conclude that the PLMA use is associated
      with lesser cardiovascular response and rise in IOP as compared to tracheal
      intubation.

PMID- 22869939
TI  - Pressure-controlled inverse ratio ventilation using laryngeal mask airway in
      gynecological laparoscopy.
AB  - BACKGROUND: It is well documented that pressure-controlled ventilation (PCV)
      improves oxygenation and ventilation compared to volume-controlled ventilation
      and reduces peak airway pressure in gynecological laparoscopy. PCV with
      moderately inversed inspiratory-expiratory (I: E) ratio can successfully recruit
      collapsed alveoli and has been proved to be beneficial in intensive care. We
      tested the hypothesis that altering the I: E ratio to 1.5:1 in PCV improves
      ventilation during gynecological laparoscopy using laryngeal mask airway (LMA).
      OBJECTIVE: To study pressure-controlled inverse ratio ventilation (PCIRV) with I:
      E ratio 1.5:1 as against PCV with I: E ratio 1:2 in gynecological laparoscopy
      with LMA using noninvasive parameters. MATERIALS AND METHODS: Intraoperative
      hemodynamics and side-stream spirometry recordings were noted in 20 consecutive
      patients undergoing major gynecological laparoscopy with LMA. Flexible LMA or LMA
      supreme were used depending on normal body mass index (BMI) or high BMI,
      respectively. RESULTS: REVERSING THE I: E ratio to 1.5:1 increased the tidal
      volume, mean airway pressures, and dynamic lung compliance significantly, all
      indicating better oxygenation at comparable peak airway pressures as against PCV
      with I: E ratio 1:2. There was no change in the end-tidal carbon dioxide. There
      was no auto-positive end expiratory pressure (PEEP) or change in the
      hemodynamics. CONCLUSION: REVERSAL OF I: E ratio with PCV can be beneficially
      used with LMA in laparoscopy.

PMID- 22869940
TI  - Dexmedetomidine as an anesthetic adjuvant in laparoscopic surgery: An
      observational study using entropy monitoring.
AB  - BACKGROUND: Dexmedetomidine is a highly selective alpha(2) agonist with
      properties of sedation, analgesia and anxiolysis, making it an ideal anesthetic
      adjuvant. Using an anesthetic adjuvant that decreases requirement of anesthetics
      and analgesics may predispose the patient to awareness. We monitored the depth of
      anesthesia (DOA) using entropy to avoid unwanted awareness under anesthesia.
      MATERIALS AND METHODS: 30 patients, American Society of Anesthesiologists grade I
      and II, aged between 18 to 50 years of either gender undergoing laparoscopic
      surgeries under general anesthesia were studied. Loading dose infusion of
      dexmedetomidine was started 1 mcg/kg for 15 minutes and patients were
      premedicated. Routine induction with propofol and fentanyl was carried out, and
      maintenance infusion of dexmedetomidine 0.2 mcg/kg/hr was given. Patients were
      monitored with standard monitoring, and in addition, the DOA was monitored with
      entropy. RESULTS: A 62.5% reduction (0.75 mg/kg) in the induction dose of
      propofol was observed, with a 30% less end-tidal concentration of isoflurane
      requirement for maintenance of anesthesia, while maintaining the adequate DOA.
      CONCLUSION: Dexmedetomidine is an effective anesthetic adjuvant that can be
      safely used in laparoscopy without the fear of awareness under anesthesia.

PMID- 22869941
TI  - Efficacy of the subcostal transversus abdominis plane block in laparoscopic
      cholecystectomy: Comparison with conventional port-site infiltration.
AB  - BACKGROUND: Pain experienced following laparoscopic cholecystectomy is largely
      contributed by the anterior abdominal wall incisions. This study investigated
      whether subcostal transversus abdominis (STA) block was superior to traditional
      port-site infiltration of local anesthetic in reducing postoperative pain, opioid
      consumption, and time for recovery. MATERIALS AND METHODS: Forty-three patients
      presenting for day case laparoscopic cholecystectomy were randomly allocated to
      receive either an ultrasound-guided STA block (n = 21) or port-site infiltration
      of local anesthetic (n = 22). Visual analog pain scores were measured at 1 and 4
      h postoperatively to assess pain severity, and opioid requirement was measured in
      recovery and up to 8 h postoperatively. The time to discharge from recovery was
      recorded. RESULTS: STA block resulted in a significant reduction in serial visual
      pain analog score values and significantly reduced the fentanyl requirement in
      recovery by >35% compared to the group that received local port-site infiltration
      (median 0.9 vs. 1.5 MUcg/kg). Furthermore, STA block was associated with nearly a
      50% reduction in overall 8-h equivalent morphine consumption (median 10 mg vs. 19
      mg). In addition, STA block significantly reduced median time to discharge from
      recovery from 110 to 65 min. CONCLUSION: The results suggest that STA block
      provides superior postoperative analgesia and reduces opioid requirement
      following laparoscopic cholecystectomy. It may also improve theater efficiency by
      reducing time to discharge from the recovery unit.

PMID- 22869942
TI  - The correlation of antepartum upper extremity cuff algometry with epidural
      analgesic requirements for labor.
AB  - BACKGROUND: Individual parturients experience pain differently, and it is unknown
      how these differences affect their requirements for labor analgesics. MATERIALS
      AND METHODS: Cuff algometry of the upper limb was used to determine the pain
      thresholds and temporal summation of pain scores in nulliparous women about to
      undergo induction of labor. Analgesia was provided, upon request, with a patient
      controlled epidural analgesia infusion of bupivacaine and fentanyl. Nurse
      administered epidural boluses of bupivacaine or lidocaine were given for
      breakthrough pain. Partial Spearman correlations were used to correlate the cuff
      algometry measurements with the amount of analgesic medication required by the
      patient. RESULTS: There was no significant correlation between any of the
      algometry measurements and the number of patient or nurse administered
      bupivacaine boluses. There was a correlation of 0.7 (P = 0.001) between the
      temporal summation scores and the hourly number of nurse-administered epidural
      lidocaine boluses; however, this was based on only 3 patients who required
      lidocaine boluses. CONCLUSIONS: The use of pre-labor cuff algometry of the upper
      limb does not correlate with the patient epidural analgesic requirements and
      subsequent analgesia administration.

PMID- 22869943
TI  - Effects of bispectral index monitoring on isoflurane consumption and recovery
      profiles for anesthesia in an elderly asian population.
AB  - BACKGROUND: Age related limited physiological reserves and associated co
      morbidities in elderly patients require careful titration of inhalational
      anesthetic agents to minimize their side effects. The use of Bispectral index
      (BIS) monitoring may be helpful in this regard. The objectives of this study were
      to evaluate the effect of BIS monitoring on Isoflurane consumption during
      maintenance and recovery profile at the end of anesthesia. This Quasi
      experimental study was conducted for a 1 year period at the main operating units
      of a tertiary care hospital. MATERIALS AND METHODS: Total 60 patients of age 60
      years and above were enrolled in either standard practice (SP) or (BIS) group. In
      the SP group, the anesthesia depth was maintained as a routine clinical practice,
      while in BIS group it was maintained by monitoring the BIS score between 45 and
      55. Standard anesthesia care was provided to all of the patients. Data including
      demographics, isoflurane consumption, hemodynamic variables and recovery profiles
      were recorded in both groups. RESULTS: The mean isoflurane consumption was lower
      (P = 0.001) in the BIS group. The time to eye opening, extubation and ready to
      shift was shorter (P = 0.0001) in BIS group. The patients in BIS group had higher
      Post anesthesia recovery score (P = 0.0001) than the SP group. CONCLUSION: The
      use of BIS in an elderly Asian population resulted in 40% reduction of isoflurane
      usage. The patients having BIS monitoring awoke earlier and had better recovery
      profiles at the end of anesthesia.

PMID- 22869944
TI  - A comparison of propofol and thiopentone for electroconvulsive therapy.
AB  - OBJECTIVES: To compare propofol and thiopental as anesthetic agents for
      electroconvulsive therapy (ECT) with respect to seizure duration, stimulus
      charge, and clinical effects. MATERIALS AND METHODS: Randomized, blinded study of
      28 patients of depression treated with bilateral ECT. In group P (n = 14),
      sedation was achieved with propofol 1.5 mg/kg, whereas in group T (n = 14), it
      was achieved with thiopentone 3 mg/ kg IV. Succinylcholine 0.4 mg/kg intravenous
      was given in all patients as for neuromuscular blockade. RESULTS: The mean
      seizure duration of the patients in the thiopental group was 83 +/- 34.43 seconds
      vs. 94.45 +/- 21.37 seconds in the propofol group (P < 0.01). The energy
      delivered per treatment was 10.88 +/- 4.78 J in the thiopental group vs. 12.20 +/
      4.53 J in the propofol group (P < 0.05). Number of ECTs required were
      significantly higher in propofol group (9.71 +/- 2.87) as compared to thiopental
      group (5.86 +/- 0.36) P < 0.0001. No significant difference in duration of
      hospitalization was seen in both groups. The mean score on Mini-Mental State
      Examination (MMSE) was 29.14 in the thiopental group vs. 29.57 in the propofol
      group (P > 0.05). The mean score on Beck Depression Inventory (BDI) was 7.14 in
      the thiopental group vs. 3.29 in the propofol group (P < 0.05). CONCLUSIONS:
      Propofol significantly increases number of ECT required to treat although the
      patients received higher electrical charge and had longer seizure duration. BDI
      scores suggest this resulted in better outcome. Results, however, might be
      confounded by the differences in pharmacological treatment in the groups.

PMID- 22869945
TI  - Endotracheal intubation under local anesthesia and sedation in an infant with
      difficult airway.
AB  - Management of the difficult airway in an infant is a challenge for the
      anesthesiologist. A 10-month-old infant presented to an otolaryngologist with
      nasopharyngeal mass since birth, which had increased rapidly in size in the last
      1 month and was hanging through the cleft palate into the oropharynx. The infant
      was scheduled for excision of the nasopharyngeal mass through a maxillary
      approach and the tongue mass through an oral approach under general anesthesia.
      This case report describes endotracheal intubation performed successfully under
      sedation and local anesthesia in an infant with a nasal mass protruding through
      the cleft palate into the oropharynx.

PMID- 22869946
TI  - Infant with unanticipated difficult airway - TrachlightTM to the rescue.
AB  - Lighted stylets may be used for assisting in oral intubation in both adult as
      well as pediatric age groups. We report the anesthetic management of an 11- month
      old infant with fractured mandible where the airway was secured with tracheal
      lightwand-guided nasal intubation after the failure of repeated attempts of
      conventional laryngoscopy.

PMID- 22869947
TI  - Combined mucopolysaccharidosis type VI and congenital adrenal hyperplasia in a
      child: Anesthetic considerations.
AB  - We present a child posted for magnetic resonance imaging of brain under general
      anesthesia with the rare combination of mucopolysachharidosis type VI and
      congenital adrenal hyperplasia. The presence of both these disorders has
      important anesthetic implications. The pathophysiology of this rare combination
      of disease is reviewed with emphasis on the anesthesia management.

PMID- 22869948
TI  - Midazolam-induced acute dystonia reversed by diazepam.
AB  - Midazolam can induce acute dystonia in childhood. We report the development of
      acute dystonia in a 6-year-old girl after receiving midazolam as a sedative.
      Dystonic contractions persisted despite flumazenil and biperiden lactate
      injections and the patient was treated with diazepam. Acute dystonia was rapidly
      abolished after the administration of diazepam intravenously. Diazepam may be an
      effective treatment option in patients who are unresponsive to flumazenil.

PMID- 22869949
TI  - Rhythmic movement disorder after general anesthesia.
AB  - Dystonic movements after general anesthesia are very rare. The differential
      diagnosis includes adverse drug reaction, local anesthetic reaction, emergence
      delirium, hysterical response, and shivering. We present a case of a 10-year-old,
      otherwise healthy girl undergoing outpatient foot surgery. Involuntary jerking
      movements of her arms and torso every time she would drift off to sleep started
      about 2.5 hours after emergence from general anesthesia. The patient was easily
      arousable and absolutely unaware of the movements. These movements lasted for
      several days before they resolved completely. We believe to present the first
      case of sleep-related rhythmic movement disorder after general anesthesia,
      considering the nature of the movements in our patient.

PMID- 22869950
TI  - Intraoperative neurological event during cesarean section under spinal anesthesia
      with fentanyl and bupivacaine: Case report and review of literature.
AB  - Neurological events similar to transient ischemic attack in a peripartum woman
      are uncommon. Cerebral complications of preeclampsia, thrombo-embolic phenomena,
      or high spinal can mimic such situations. Spinal anesthesia with local anesthetic
      and opioid is an established anesthetic technique for cesarean section. Although
      intrathecal opioids are safe for both the mother and fetus; some unusual
      complications such as dysphagia alone or associated with facial numbness,
      aphasia, have been reported. We report a case of transient aphonia and tingling
      sensation over the face without any dysphagia after intrathecal administration of
      bupivacaine and fentanyl for cesarean section.

PMID- 22869951
TI  - Do the clinical parameters provide the reliable indication of airway findings in
      adult patients with acute supraglottitis?
AB  - Airway management of adult patients with acute supraglottitis is challenging. The
      sign and symptoms of the disease may show marked variation in terms of severity
      and progression. Thorough evaluation is required before selecting any particular
      approach. We report the case of an adult patient with acute supraglottitis, in
      whom active airway intervention was planned. The clinical predictors were not
      suggestive of any airway compromise in our patient. However, the disease was
      found to have an unanticipated rapidly progressive course leading to the
      significant edema of the oropharynx and the surrounding structures as evidenced
      by the laryngoscope and computerized tomography scan findings.

PMID- 22869952
TI  - Sudden endotracheal tube block in a patient of Achalasia Cardia.
AB  - Endotracheal tube block due to various mechanical causes such as mucous, blood
      clot, denture, and ampoules have been reported. A patient of achalasia cardia
      with chronic passive aspiration pneumonitis developed mucoid mass in the
      respiratory passage which dislodged during the surgical procedure. The episode
      occurred almost an hour after induction of anesthesia and the dislodged mucoid
      mass blocked the lumen of endotracheal tube, leading to hypoxia and impending
      cardiac arrest. However, the patient was salvaged by replacing the tube.

PMID- 22869953
TI  - A case of single atrium and single ventricle physiology with bilateral cleft lip
      and palate for lip repair surgery.
AB  - Bilateral cleft lip and palate may occasionally be associated with complex
      congenital cyanotic heart disease. An infant with common atrium and single
      ventricle with infundibular pulmonary stenosis (Blalock-Taussig shunt done
      recently) presented for lip repair surgery. Balanced general anesthesia was
      administered using sevoflurane along with a regional nerve block to maintain
      optimal pulmonary and systemic vascular resistance.

PMID- 22869954
TI  - Renal replacement therapy in ICU.
AB  - Diagnosing and managing critically ill patients with renal dysfunction is a part
      of the daily routine of an intensivist. Acute kidney insufficiency substantially
      contributes to the morbidity and mortality of critically ill patients. Renal
      replacement therapy (RRT) not only does play a significant role in the treatment
      of patients with renal failure, acute as well as chronic, but also has spread its
      domains to the treatment of many other disease conditions such as myaesthenia
      gravis, septic shock and acute on chronic liver failure. This article briefly
      outlines the role of renal replacement therapy in ICU.

PMID- 22869955
TI  - Tracheal intubation through Igel conduit in a child with post-burn contracture.

PMID- 22869956
TI  - Anesthetic management of a child with Seckel syndrome for multiple extractions
      and restoration of teeth.

PMID- 22869957
TI  - Anesthetic management of an unusual complication during laser ablation of
      congenital subglottic hemangioma.

PMID- 22869959
TI  - Management of intraoperative penile erection with salbutamol aerosol.

PMID- 22869958
TI  - AMBU Laryngeal Mask Airway: A useful aid in post-burn contracture of neck.

PMID- 22869960
TI  - Piperacillin/tazobactem induced epistaxis- A case report.

PMID- 22869961
TI  - Postoperative hyperpyrexia: Retracing malignant hyperthermia.

PMID- 22869962
TI  - Masseteric muscle spasm following neostigmine.

PMID- 22869963
TI  - Severe hypotension following spinal anesthesia in patients on amlodipine.

PMID- 22869964
TI  - Effective analgesia after cesarean delivery needs pharmacokinetic input.

PMID- 22869965
TI  - Response to the letter for the article - Observational study to assess the
      effectiveness of postoperative pain management of patients undergoing elective
      caesarean section.

PMID- 22869966
TI  - 0.5% hyperbaric bupivacaine - Do we still need a 4 ml ampoule?

PMID- 22869967
TI  - Inhaled anesthetics contributing to drug wastage.

PMID- 22869968
TI  - Anesthetic management of a case of transtentorial upward herniation: An uncommon
      emergency situation.

PMID- 22869969
TI  - An unusual cause of delayed recovery from anesthesia.

PMID- 22869970
TI  - A stitch in time saves nine.

PMID- 22869971
TI  - A simple method to protect tracheal cuff of double lumen tube from damage during
      intubation.

PMID- 22869972
TI  - Persistent hiccup after lumbar epidural steroid injection.

PMID- 22869973
TI  - Persistent hyperinsulinemic hypoglycemia of infancy: An overview of current
      concepts.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is relatively rare but
      one of the most important causes of severe neonatal hypoglycemia. Recognition of
      this entity becomes important due to the fact that the hypoglycemia is so severe
      and frequent that it may lead to severe neurological damage in the infant
      manifesting as mental or psychomotor retardation or even a life-threatening event
      if not recognized and treated effectively in time. Near-total pancreatectomy may
      be required for patients with intractable hypoglycemia despite medical treatment;
      however, that may result in diabetes mellitus or recurrent postoperative
      hypoglycemia. This review aims to consolidate the traditional concepts and
      current information related to the pathogenesis and management of PHHI.

PMID- 22869974
TI  - Splenosis after splenectomy and spleen tissue autoimplantation: Late followup
      study.
AB  - AIM: In children suffering from severe hepatosplenic schistosomiasis, the
      surgical protocol includes splenectomy and autoimplantation of spleen morsels in
      the major omentum, which has the potential of reducing the overwhelming
      postsplenectomy infection (OPSI). The purpose of the study was to evaluate the
      remaining splenosis, with the mean postoperative followup of 12.1 +/- 5.6 years;
      to compare the efficacy of the 2 evaluation tools. MATERIALS AND METHODS:
      Nineteen patients underwent, when they were children, portal decompression and
      autoimplantation of spleen. After a mean age of 23.4 +/- 5.3 years, they were
      investigated regarding the number of infections and OPSI. They had undergone
      hepatosplenic scintigraphy with labeled colloidal SnTc(99m) and abdominal
      ultrasound. It was considered efficient splenosis when the patients presented
      with 5 or more spleen nodules. The evaluation was performed by 3 observers.
      RESULTS: None of the patients had increased infection rate or developed OPSI.
      Sixteen (84.2%) presented efficient splenosis. CONCLUSIONS: The remaining
      postoperative splenosis was considered efficient in the majority of patients in
      the long-term followup; and nuclear medicine was considered the gold standard for
      splenosis evaluation.

PMID- 22869975
TI  - Esophageal atresia associated with anorectal malformation: Is the outcome better
      after surgery in two stages in a limited resources scenario?
AB  - AIMS: To analyze whether outcome of neonates having esophageal atresia with or
      without tracheoesophageal fistula (EA+/-TEF) associated with anorectal
      malformation (ARM) can be improved by doing surgery in 2 stages. MATERIALS AND
      METHODS: A prospective study of neonates having both EA+/-TEF and ARM from 2004
      to 2011. The patients with favorable parameters were operated in a single stage,
      whereas others underwent first-stage decompression surgery for ARM. Thereafter,
      once septicemia was under control and ventilator care available, second-stage
      surgery for EA+/-TEF was performed. RESULTS: Total 70 neonates (single stage =
      20, 2 stages = 30, expired after colostomy = 9, only EA+/-TEF repair needed = 11)
      were enrolled. The admission rate for this association was 1 per 290. Forty-one
      percent (24/70) neonates had VACTERL association and 8.6% (6/70) neonates had
      multiple gastrointestinal atresias. Sepsis screen was positive in 71.4% (50/70).
      The survival was 45% (9/20) in neonates operated in a single stage and 53.3%
      (16/30) when operated in 2 stages (P = 0.04). Data analysis of 50 patients
      revealed that the survived neonates had significantly better birth weight, better
      gestational age, negative sepsis screen, no cardiac diseases, no pneumonia, and 2
      stage surgery (P value 0.002, 0.003, 0.02, 0.02, 0.04, and 0.04, respectively).
      The day of presentation and abdominal distension had no significant effect (P
      value 0.06 and 0.06, respectively). This was further supported by stepwise
      logistic regression analysis. CONCLUSIONS: In a limited resources scenario, the
      survival rate of babies with this association can be improved by treating ARM
      first and then for EA+/-TEF in second stage, once mechanical ventilator care
      became available and sepsis was under control.

PMID- 22869976
TI  - Urethral duplication: Experience of four cases.
AB  - AIM: Our experience of 4 cases of urethral duplication is reported here.
      MATERIALS AND METHODS: A retrospective chart review. RESULTS: The age at
      presentation varied from newborn to 10 years. The clinical presentation ranged
      from prepubic sinus to diphallus urethra. There were 2 each incomplete
      duplication with only external openings (Type IA) and complete duplication of
      Effmann Type IIA2. All underwent complete excision of accessory urethra and
      corrections of associated anomalies. CONCLUSIONS: Urethral duplications have a
      varied presentation. At follow up, all are asymptomatic with good cosmetic
      result.

PMID- 22869977
TI  - Surgical complications of Ascaris lumbricoides in children.
AB  - AIM: To report the surgical complications of Ascaris lumbricoides infestation in
      children. MATERIALS AND METHODS: This is a retrospective study and cases of
      intestinal ascariasis managed conservatively were excluded. RESULTS: Sixteen
      children presented with Ascariasis sequelae, which included ileal volvulus (n=5),
      perforations (n=4), intussusception (n=1), biliary ascariasis (n-1) and impacted
      multiple worm boluses (n=5). Plain abdominal radiographs showed pneumoperitoneum
      (3), cigar bundle appearance (3) and multiple air and fluid levels (13).
      Sonography showed floating worms with free fluid (2), sluggish peristalsis and
      moderate free fluid (7) and intestinal worm bolus (11). The surgical procedures
      included milking of worms (in all), bowel resection (6), closure of perforation
      (3) and manual reduction of intussusception (1). Biliary ascariasis was managed
      conservatively and the progress monitored with sonography. There were 3 deaths
      all of whom had intestinal volvulus, bowel necrosis and toxemia. CONCLUSION:
      Sonography can be helpful in diagnosing the presence of worms, its complications
      and in evaluating response to treatment. Early surgical intervention in those
      with worm bolus, peritonism, and volvulus may salvage bowel and reduce mortality.

PMID- 22869978
TI  - Anorectal malformations: Definitive management during and beyond adolescence.
AB  - AIM: To evaluate our results of definitive repair of anorectal malformations in
      patients with delayed presentation, during and beyond adolescence. MATERIAL AND
      METHODS: It is a retrospective analysis of all adolescent patients presenting for
      the first time for definitive repairs and innate patients - colostomy performed
      during the neonatal period, but who had lost to follow-up. It includes 15
      patients (2 male and 13 female) aged from 13 to 32 years. Three well-decompressed
      female patients were managed by primary anterior sagittal anorectoplasty (ASARP).
      Twelve patients underwent staged procedures. Five patients (two male and three
      female) underwent posterior sagittal anorectoplasty (PSARP). The oldest male
      patient underwent abdominal-PSARP. RESULTS: All of them attained socially
      acceptable fecal continence at follow-up of 1-41/2 years. They are satisfied with
      the functional and cosmetic outcome of repair of their anomalies. CONCLUSIONS:
      Prospects of fecal continence are good when definitive repair of anorectal
      malformations is done by an expert, even in the adolescent age group and beyond.

PMID- 22869979
TI  - Extrarenal calyces associated with pelviureteric junction obstruction: A case
      report of a rare anomaly.
AB  - Extrarenal calyces are one of the rare renal anomalies associated with the
      collecting system. Their association with renal ectopia or horse shoe kidney is
      known. But, here in, we are reporting an intraoperative surprise, where
      extrarenal calyces were associated with pelviureteric junction obstruction and
      routine preoperative imaging did not show any light on the diagnosis.

PMID- 22869980
TI  - Posterior urethral valves and Cowper's syringocele: A rare association causing
      voiding dysfunction.
AB  - Urethral syringoceles are cystic dilatations of paired bulbourethral glands of
      Cowper. They can cause voiding dysfunction in male children and usually occur in
      isolation. We report a rare association of Cowper's syringocele with posterior
      urethral valves in a 4-year-old child, which was successfully managed
      endoscopically.

PMID- 22869981
TI  - Amyand's hernia presenting as chronic scrotal sinus.
AB  - A rare case of Amyand's hernia in an infant who presented with chronic
      discharging scrotal sinus is reported.

PMID- 22869982
TI  - A rare mode of entry for needles observed in the abdomen of children:
      Penetration.
AB  - REPORT OF INCIDENTALLY DETECTED SEWING NEEDLES ON PLAIN ABDOMINAL RADIOGRAPHS IN
      TWO PATIENTS WITHOUT ANY PRIOR HISTORY OF INGESTION OR OF BEING PIERCED: one in
      the liver and the other in the peritoneum encased by omentum. These case reports
      point out a rare mode of entry of needles into the abdominal cavity by
      penetration from outside.

PMID- 22869983
TI  - Isolated mucormycosis in a post-pyeloplasty kidney in an immuno-competent child.
AB  - A child with isolated renal mucormycosis who was successfully treated with
      systemic anti-fungal therapy and nephrectomy is reported.

PMID- 22869984
TI  - Locally invasive pulmonary inflammatory myofibroblastic tumors in children.
AB  - Two uncommon cases of locally invasive pulmonary inflammatory myofibroblastic
      tumor are reported. Diagnosis was established by a prior thoracotomy and
      incisional biopsy. Complete excision was curative and both children remain
      asymptomatic at last follow up.

PMID- 22869985
TI  - Malrotation and volvulus associated with heterotaxy syndrome.
AB  - A 2-year-old boy with heterotaxy syndrome with associated polysplenia,
      ventricular septal defect, and malrotation of gut with volvulus is presented.
      There was delay in diagnosis due to the unusual plain abdominal radiography
      findings. At laparotomy, the midgut was also found to be enclosed in a thin
      transparent cocoon.

PMID- 22869986
TI  - Soft tissue covers in hypospadias surgery: Is tunica vaginalis better than dartos
      flap?

PMID- 22869987
TI  - Authors' reply.

PMID- 22869988
TI  - Live operative workshops: Should we do away with them?

PMID- 22869989
TI  - Models and mechanisms in yoga research.

PMID- 22869990
TI  - Yoga therapy for Schizophrenia.
AB  - Schizophrenia is one of the most severe mental disorders. Despite significant
      advances in pharmacotherapy, treatment remains sub-optimal, with many patients
      having persisting deficits, especially in cognitive and social functioning. Yoga
      as a therapy has proven to be effective as a sole or additional intervention in
      psychiatric disorders such as depression and anxiety. Recently, there has been
      significant interest in the application of yoga therapy in psychosis and
      schizophrenia. To review a) the evidence for the use of yoga therapy in patients
      with schizophrenia b) studies which have been done in this area, c) the barriers
      for reaching yoga to patients, and d) future directions, an English language
      literature search of PubMed/MEDLINE, Google Scholar, and EBSCO as well as grey
      literature was done. Research reports have demonstrated the feasibility and
      efficacy of yoga as an add-on therapy in schizophrenia, particularly in improving
      negative symptomatology and social cognition. However, the biological
      underpinnings of this effect remain unclear, although there are some indications
      that hormones like oxytocin may contribute to the changes in social cognition.

PMID- 22869991
TI  - Yoga in Australia: Results of a national survey.
AB  - INTRODUCTION: The therapeutic benefits of yoga and meditation are well
      documented, yet little is known about the practice of yoga in Australia or
      elsewhere, whether as a physical activity, a form of therapy, a spiritual path or
      a lifestyle. MATERIALS AND METHODS: To investigate the practice of yoga in
      Australia, a national survey of yoga practitioners was conducted utilizing a
      comprehensive web-based questionnaire. Respondents were self-selecting to
      participate. A total of 3,892 respondents completed the survey. Sixty overseas
      respondents and 1265 yoga teachers (to be reported separately) were excluded,
      leaving 2,567 yoga practitioner respondents. RESULTS: The typical yoga survey
      respondent was a 41-year-old, tertiary educated, employed, health-conscious
      female (85% women). Asana (postures) and vinyasa (sequences of postures)
      represented 61% of the time spent practicing, with the other 39% devoted to the
      gentler practices of relaxation, pranayama (breathing techniques), meditation and
      instruction. Respondents commonly started practicing yoga for health and fitness
      but often continued practicing for stress management. One in five respondents
      practiced yoga for a specific health or medical reason which was seen to be
      improved by yoga practice. Of these, more people used yoga for stress management
      and anxiety than back, neck or shoulder problems, suggesting that mental health
      may be the primary health-related motivation for practicing yoga. Healthy
      lifestyle choices were seen to be more prevalent in respondents with more years
      of practice. Yoga-related injuries occurring under supervision in the previous 12
      months were low at 2.4% of respondents. CONCLUSIONS: Yoga practice was seen to
      assist in the management of specific health issues and medical conditions.
      Regular yoga practice may also exert a healthy lifestyle effect including
      vegetarianism, non-smoking, reduced alcohol consumption, increased exercise and
      reduced stress with resulting cost benefits to the community.

PMID- 22869992
TI  - Yoga breathing through a particular nostril is associated with contralateral
      event-related potential changes.
AB  - BACKGROUND: In earlier studies uninostril yoga breathing was shown to influence
      the activity of the cerebral hemispheres differently, based on (i) auditory
      evoked potentials recorded from bilateral scalp sites, and (ii) performance in
      hemisphere-specific tasks. But change in P300 (event-related potential generated
      when subjects attend to and discriminate between stimuli) from bilateral scalp
      sites when subjects were practicing uni- and alternate-nostril breathing are yet
      to be explored. AIM: The present study was designed to determine whether or not
      immediately after uninostril or alternate nostril yoga breathing there would be a
      change in the ability to pay attention to a given stimulus. MATERIALS AND
      METHODS: Twenty-nine healthy male volunteers, with ages between 20 and 45 years
      were randomly allocated to five sessions, viz., (i) right-, (ii) left-, (iii)
      alternate-nostril yoga breathing, (iv) breath awareness and (v) no intervention,
      each for 45 min on separate days. The P300 event related potential was recorded
      using an auditory oddball paradigm from sites on the left (C3) and right (C4),
      referenced to linked earlobes, before and after each session. RESULTS: Post-hoc
      analysis with Bonferroni adjustment showed that the P300 peak latency was
      significantly lower at C3 compared to that at C4, following right nostril yoga
      breathing (P<0.05). CONCLUSION: These results suggest that right nostril yoga
      breathing facilitates the activity of contralateral (left) hemisphere, in the
      performance of the P300 task.

PMID- 22869993
TI  - Immediate effect of chandra nadi pranayama (left unilateral forced nostril
      breathing) on cardiovascular parameters in hypertensive patients.
AB  - INTRODUCTION: Recent studies have reported differential physiological and
      psychological effects produced by exclusive right and left nostril breathing and
      clinical research is required to prove immediate and sustained efficacy of these
      techniques in various psychosomatic conditions such as hypertension (HT). The
      present study was designed to determine immediate effects of 27 rounds of
      exclusive left nostril breathing, a yogic pranayama technique known as chandra
      nadi pranayama (CNP) on cardiovascular parameters in patients of essential HT.
      MATERIALS AND METHODS: Twenty two patients of essential HT under regular standard
      medical management were individually taught to perform CNP by a qualified yoga
      instructor with a regularity of 6 breaths/min throughout a performance of 27
      rounds of CNP. Pre and post intervention heart rate (HR) and blood pressure (BP)
      measurements were recorded using non-invasive semi-automatic BP monitor and
      Students t test for paired data used to determine significant differences.
      RESULTS: Twenty seven rounds of CNP produced an immediate decrease in all the
      measured cardiovascular parameters with the decrease in HR, systolic pressure
      (SP), pulse pressure, rate-pressure product and double product being
      statistically significant. Further, gender-based sub-analysis of our data
      revealed that our male participants evidenced significant reductions in HR and SP
      with an insignificant decrease in diastolic pressure, while in female
      participants only HR decreased significantly with an insignificant decrease in
      SP. DISCUSSION AND CONCLUSION: It is concluded that CNP is effective in reducing
      HR and SP in hypertensive patients on regular standard medical management. To the
      best of our knowledge, there are no previously published reports on immediate
      effects of left UFNB in patients of HT and ours is the first to report on this
      beneficial clinical effect. This may be due to a normalization of autonomic
      cardiovascular rhythms with increased vagal modulation and/or decreased
      sympathetic activity along with improvement in baroreflex sensitivity. Further
      studies are required to enable a deeper understanding of the mechanisms involved
      as well as determine how long such a BP lowering effect persists. We recommend
      that this simple and cost effective technique be added to the regular management
      protocol of HT and utilized when immediate reduction of BP is required in day-to
      day as well as clinical situations.

PMID- 22869994
TI  - Effect of holistic yoga program on anxiety symptoms in adolescent girls with
      polycystic ovarian syndrome: A randomized control trial.
AB  - CONTEXT: Yoga techniques practiced for varying durations have been shown to
      reduce state anxiety. This was never assessed in adolescents with polycystic
      ovarian syndrome (PCOS). AIMS: To compare the effect of a holistic yoga program
      with the conventional exercise program on anxiety level in adolescents with PCOS.
      SETTINGS AND DESIGN: Ninety adolescent (15-18 years) girls from a residential
      college in Andhra Pradesh, who satisfied the Rotterdam criteria, were randomized
      into two groups. MATERIALS AND METHODS: Anxiety levels were assessed at inclusion
      and after 12 weeks of intervention wherein yoga group practiced a holistic yoga
      module while the control group practiced a matching set of physical exercises (1
      h/day, for 12 weeks). STATISTICAL ANALYSIS USED: Mann-Whitney U test was used to
      compare difference scores (delta change) between the two groups RESULTS: Changes
      in state anxiety after the intervention were nonsignificantly different between
      the two groups (P=0.243), while changes after the intervention were significantly
      different between the two groups (P=0.002) for trait anxiety. CONCLUSIONS: Twelve
      weeks of a holistic yoga program in adolescents with PCOS is significantly better
      than physical exercise program in reducing anxiety symptoms.

PMID- 22869995
TI  - Comparative study of conventional therapy and additional yogasanas for knee
      rehabilitation after total knee arthroplasty.
AB  - BACKGROUND: Amongst various modalities of post operative rehabilitation in a
      total knee replacement (TKR) surgery, this study focuses on evaluating the effect
      of additional yoga therapy on functional outcome of TKR patients. MATERIALS AND
      METHODS: A comparative study was done to compare the effects of conventional
      physiotherapy and additional yoga asanas, on 56 patients undergoing total knee
      arthroplasty due to osteoarthritis. After obtaining written informed consent, the
      patients were alternately assigned to two groups: Conventional and experimental.
      Baseline WOMAC scores for pain and stiffness were taken on third post operative
      day. The subjects in conventional group received physiotherapy rehabilitation
      program of Sancheti Institute where the study was conducted, the experimental
      group received additional modified yoga asanas once daily by the therapist. After
      discharge from the hospital, patients were provided with written instructions and
      photographs of the asanas, two sets of WOMAC questionnaire with stamped and
      addressed envelopes and were instructed to perform yoga asanas 3 days/week.
      Subjects filled the questionnaire after 6 weeks and 3 months from the day of
      surgery and mailed back. The primary outcome measure was WOMAC questionnaire
      which consists of 24 questions, each corresponding to a visual analog scale,
      designed to measure patient's perception of pain, stiffness and function.
      RESULTS: The results suggest that there was a significant change (P<0.05) for all
      the groups for pain, stiffness and function subscales of WOMAC scale. The pain
      and stiffness was found to be less in experimental group receiving additional
      yoga therapy than in conventional group on 3(rd) post operative day, 6 weeks and
      3 months after the surgery. CONCLUSION: A combination of physiotherapy and yoga
      asana protocol works better than only physiotherapy protocol. Larger and blinded
      study is needed.

PMID- 22869996
TI  - Study of the effect of yoga training on diffusion capacity in chronic obstructive
      pulmonary disease patients: A controlled trial.
AB  - BACKGROUND: Patients of chronic obstructive pulmonary disease (COPD) are at high
      risk for depression and anxiety. Yoga techniques are suited for promoting
      relaxation, psycho-emotional stability and exercise tolerance. Studies showing
      the effect of yoga in diffusion capacity are not available; hence this study was
      planned. MATERIALS AND METHODS: The study was conducted on 60 diagnosed stable
      mild-to-moderate COPD patients in the age group of 30-60 years, of either sex, in
      the department of physiology. Patients were taken from Guru Teg Bahadur Hospital,
      Delhi and divided into two groups: Control and the yoga group. Both the groups
      were on conventional drug therapy. Subjects from the Yoga group was called to
      cardiopulmonary laboratory daily for 21 days and then weekly for the compliance.
      Yoga instructor taught them the technique of pranayama and various postures every
      day. They practiced yoga at home for 2 months for 45 min in the mornings.
      Diffusion capacity was recorded by using computerized Medisoft instrument (HYPAIR
      compact), in both the groups before and after 2 months. RESULTS: Statistical
      analysis showed significant improvement in TLCO of the yoga group. Transfer
      factor of lung for carbon monoxide i.e. TLCO in mild COPD increased from 17.61 +/
      4.55 to 19.08 +/- 5.09 ml/mmHg/min, and in moderate COPD it increased from 14.99
      +/- 4.02 to17.35 +/- 3.97 ml/mmHg/min. CONCLUSION: It was concluded that yogic
      breathing exercises improve diffusion capacity. They are beneficial to COPD
      patients and they can be used as an adjunct therapy with the conventional medical
      therapy.

PMID- 22869997
TI  - A comparative study of the effects of yoga and swimming on pulmonary functions in
      sedentary subjects.
AB  - CONTEXT: The modality of exercise that is most beneficial and easy to perform has
      become a topic of research. Yogic exercises are being widely studied; however,
      postulated benefits of yogic exercises over other exercises must be
      scientifically explored. Prospective randomized comparative studies involving
      yoga and other endurance exercises are conspicuous by their absence. AIM: This
      study was, therefore, designed to assess and compare the effects of yogic
      training and swimming on pulmonary functions in normal healthy young volunteers.
      MATERIALS AND METHODS: 100 volunteers were inducted into the study and randomly
      divided into two groups: One group underwent 12 weeks training for yogic
      exercises and other for swimming. The training and data acquisition was done in
      small cohorts of 10 subjects each. The subjects were assessed by studying their
      anthropometric parameters and pulmonary function parameters (FVC, FEV1/FVC ratio,
      PEFR, FEF25-75%, FEF 0.2-1.2 l and MVV) both before and after training. RESULTS:
      All parameters showed statistically significant improvements after both yoga and
      swimming. Comparison of these improvements for different parameters statistically
      analyzed by unpaired t test or Mann Whitney U test depicted a statistically
      better improvement in FVC, FEF25-75% and MVV with swimming as compared to yogic
      exercises. CONCLUSIONS: The output of this study gives slight edge to swimming as
      a preferred modality of exercise though either yoga or swimming can be advocated
      as an exercise prescription as both the modalities cause significant improvement
      of respiratory health. However, other factors like ability of any exercise regime
      to keep continued motivation and interest of the trainees must be taken into
      account for exercise prescription.

PMID- 22869998
TI  - A short-term, comprehensive, yoga-based lifestyle intervention is efficacious in
      reducing anxiety, improving subjective well-being and personality.
AB  - OBJECTIVE: To assess the efficacy of a short-term comprehensive yoga-based
      lifestyle intervention in reducing anxiety, improving subjective well-being and
      personality. MATERIALS AND METHODS: The study is a part of an ongoing larger
      study at a tertiary care hospital. Participants (n=90) included patients with
      chronic diseases attending a 10-day, yoga-based lifestyle intervention program
      for prevention and management of chronic diseases, and healthy controls (n=45)
      not attending any such intervention. PRIMARY OUTCOME MEASURES: Change in state
      and trait anxiety questionnaire (STAI-Y; 40 items), subjective well-being
      inventory (SUBI; 40 items), and neuroticism extraversion openness to experience
      five factor personality inventory revised (NEO-FF PI-R; 60 items) at the end of
      intervention. RESULTS: Following intervention, the STAI-Y scores reduced
      significantly (P<0.001) at Day 10 (66.7 +/- 13.0) versus Day 1 (72.5 +/- 14.7).
      Also, positive SUBI scores (F1- F6) improved significantly (P<0.01) at Day 10
      versus Day 1. Similarly NEO-FF PI-R scores improved significantly (P<0.001) at
      Day 10 versus Day 1. Control group showed an increase in STAI-Y while SUBI and
      NEO-FF PI-R scores remained comparable at Day 10 versus Day 1. CONCLUSIONS: The
      observations suggest that a short-term, yoga-based lifestyle intervention may
      significantly reduce anxiety and improve subjective well-being and personality in
      patients with chronic diseases.

PMID- 22869999
TI  - Protracted parahippocampal activity associated with Sean Harribance.
AB  - AIMS: Previous research published by Venkatasubramanian et al. (2008) in this
      journal showed markedly enhanced functional magnetic resonance imaging (fMRI)
      activity within the right parahippocampal region of a gifted person while he
      experienced accurate telepathic impression. The present research is designed to
      discern if Sean Harribance, a reliable psychic who reported independently
      verified accurate histories of others during his intuitive state, would also show
      similar enhancement as measured by standardized low resolution electromagnetic
      tomography (sLORETA). MATERIALS AND METHODS AND RESULTS: The raw data from the
      unique electroencephalographic pattern displayed by Sean Harribance (the
      Harribance configuration) during his intuitive state revealed a peak increase of
      power within the upper beta range (20-30 Hz) within the right parahippocampal
      region only. CONCLUSIONS: The congruence of the region of activation during
      "telepathy" by Sean Harribance and Gerard Senehi, especially when the specific
      electromagnetic and cellular characteristics are considered, suggests the
      parahippocampal region may be a focus for exploration of the mechanisms by which
      these phenomena might occur.

PMID- 22870000
TI  - Safety and feasibility of modified chair-yoga on functional outcome among elderly
      at risk for falls.
AB  - Falls are among the most common problems affecting older adults. At least 50% of
      those over the age of 80 fall annually. The goal of this pilot study was to
      assess the safety and feasibility of structured yoga in an elderly population
      with fall risk. Seniors at risk for falls were identified and enrolled in a
      single arm pilot trial. A chair based yoga program was provided twice a week for
      8 weeks. The program was designed from previously published pilot data. A battery
      of validated instruments was administered at baseline and week eight and was used
      to identify which instruments may be sensitive to change as a result of a yoga
      program. Among sixteen seniors (median age of 88) with a previous history of
      falls, 87% provided data for assessment at the end of the intervention. Two
      patients withdrew, one due to a fall outside the institution and the other due to
      lack of time and interest. There were no adverse events during the yoga sessions.
      Paired-t tests compared pre-post changes and gains were noted in Fear of Falling
      (5.27 to 2.60; P = 0.029) and SPPB sit to stand subscale (0.31 to 1.00; P =.022).
      Improved trends were noted in anxiety and the timed up and go assessments. We
      found the modified chair-yoga program is safe and recruitment is feasible. Our
      data suggests that yoga may be beneficial in improving mobility and reducing fear
      of falling which warrants additional research via randomized controlled trial.

PMID- 22870002
TI  - Yoga, mental health and salivary amylase.

PMID- 22870001
TI  - The influence of a yoga exercise program for young adults with intellectual
      disabilities.
AB  - BACKGROUND: Individuals with intellectual disabilities (ID) have an increased
      risk of obesity and are significantly less likely to engage in physical activity
      compared to their nondisabled peers. A growing body of research supports the
      physical and mental health benefits of yoga. While the benefits of yoga have been
      studied across a host of populations with varying ages and physical disabilities,
      no studies could be identified investigating the benefits of yoga for young
      adults with ID. AIMS: This study investigated the impact of participating in yoga
      classes on the amount of exercise behavior and perception of physical exertion
      when compared to non-structured exercise sessions between two young adults with
      ID in a post-secondary education setting. MATERIALS AND METHODS: A single subject
      multiple baseline research design was implemented across two young adults with
      mild ID to determine the effects of a yoga exercise class on frequency of
      exercise behavior and perception of physical exertion when compared to non
      structured exercise sessions. Partial interval recording, the Eston-Parfitt
      curvilinear rating of perceived exertion scale, and the physical activity
      enjoyment scale were implemented to collect data on dependent variables and
      consumer satisfaction during each non-structured exercise session and each yoga
      class. RESULTS: indicated that percentage of exercise behavior and perceived
      exertion levels during yoga group exercise sharply increased with large effect
      sizes when compared to non-structured exercise sessions.

PMID- 22870003
TI  - Yoga is not an intervention but may be yogopathy is.

PMID- 22870004
TI  - Response to "Yoga is not an intervention but may be yogopathy is".

PMID- 22870005
TI  - Yoga beyond union.

PMID- 22870006
TI  - From the Editor's desk.

PMID- 22870007
TI  - Understanding implantation window, a crucial phenomenon.
AB  - Embryo implantation is a well-defined and precise process, in which various
      factors come into play one after the other. There is only a specific period of
      time during which implantation is possible i.e. "implantation window". Selectins
      were proposed to have an important role in this phase to ensure suitable rolling
      of the blastocyst. To prevent the blastocyst from adhering to an area with poor
      chances of implantation, an important role is played by the repellent activity of
      MUC-1, which is widely expressed throughout the endometrium and, surprisingly,
      even increases before implantation. In particular endometrial areas, secretion of
      chemokines and growth factors will attract the blastocyst to landing platforms
      known as pinopods. These pinopods are fully developed for only 1 or 2 days and
      extend over the tips of the microvilli expressing the repellent MUC-1. At this
      stage, adhesion molecules such as integrins and cadherins intervene to ensure
      adhesiveness between the embryo and the endometrium.

PMID- 22870008
TI  - Sample size estimation and power analysis for clinical research studies.
AB  - Determining the optimal sample size for a study assures an adequate power to
      detect statistical significance. Hence, it is a critical step in the design of a
      planned research protocol. Using too many participants in a study is expensive
      and exposes more number of subjects to procedure. Similarly, if study is
      underpowered, it will be statistically inconclusive and may make the whole
      protocol a failure. This paper covers the essentials in calculating power and
      sample size for a variety of applied study designs. Sample size computation for
      single group mean, survey type of studies, 2 group studies based on means and
      proportions or rates, correlation studies and for case-control for assessing the
      categorical outcome are presented in detail.

PMID- 22870009
TI  - Clinical outcome of one-third-dose depot triptorelin is the same as half-dose
      depot triptorelin in the long protocol of controlled ovarian stimulation.
AB  - OBJECTIVE: Appropriate dosage of the long-acting depot gonadotrophin releasing
      hormone (GnRH) agonist has not been determined in long protocol for IVF, and one
      third-dose depot triptorelin was compared with half-dose in a luteal long
      protocol of in-vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI)
      treatment in this study. MATERIALS AND METHODS: This is a prospective,
      randomized, open clinical trial. 100 patients were randomized into two groups.
      Group I received one-third-dose (1.25 mg) depot triptorelin. Group II received
      half-dose (1.87 mg). The clinical and experimental parameters were compared
      between the two groups. RESULTS: There was no premature luteinizing hormone (LH)
      surge in both groups. On Day 3-5 of menstrual cycle after down-regulation, fewer
      patients showed low-level LH (<1.0 IU/L) and estradiol (<30 pg/mL) in group I (P
      <0.05). There were fewer oocytes retrieved (P =0.086), fewer total embryos and
      available embryos for cryopreservation in Group I (P <0.05), while good-quality
      embryo rate was higher in group I (P <0.05). The length and dose of ovarian
      stimulation was lower in Group I, but not significantly. The clinical pregnancy
      (52% versus 40%), implantation (48% versus 37.5%), delivery (46% versus 32%), or
      live birth (42% versus 32%) rates and the abortion (8% versus 20%) rates showed
      no significant differences. CONCLUSION: Depot triptorelin 1.25 mg can be
      successfully used with reduced pituitary suppression and lower cost in a long
      protocol for in-vitro fertilization.

PMID- 22870010
TI  - A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene
      citrate in induction of ovulation in polycystic ovarian syndrome.
AB  - OBJECTIVES: To compare the efficacy of letrozole and clomiphene citrate (CC) in
      patients of anovulatory polycystic ovarian syndrome (PCOS) with infertility.
      MATERIALS AND METHODS: This prospective randomized clinical trial included 204
      patients of PCOS. 98 patients (294 cycles) received 2.5-5 mg of letrozole; 106
      patients (318 cycles) received 50-100 mg of CC (both orally from Days 3-7 of
      menstrual cycle). The treatment continued for three cycles in both the groups.
      MAIN OUTCOME MEASURES: ovulation rate, endometrial thickness, and pregnancy rate.
      Statistical analysis was done using SPSS 13 software. P value less than 0.05 was
      considered significant. RESULTS: The mean number of dominant follicles in
      letrozole groups and CC groups was 1.86+/-0.26 and 1.92+/-0.17, respectively
      (P=0.126). Number of ovulatory cycle in letrozole group was 196 (66.6%) versus
      216 (67.9%) in CC group (P=0.712). The mean mid-cycle endometrial thickness was
      9.1+/-0.3 mm in letrozole group and 6.3+/-1.1 in CC group, which was
      statistically significant (P=0.014). The mean Estradiol [E2] level in clomiphene
      citrate group was significantly higher in CC group (364.2+/-71.4 pg/mL) than
      letrozole group (248.2+/- 42.2 pg/mL). 43 patients from the letrozole group
      (43.8%) and 28 patients from the CC group (26.4%) became pregnant. CONCLUSION:
      Letrozole and CC have comparable ovulation rate. The effect of letrozole showed a
      better endometrial response and pregnancy rate compared with CC.

PMID- 22870011
TI  - Prevalence of metabolic syndrome in women with polycystic ovary syndrome
      attending an infertility clinic in a tertiary care hospital in south India.
AB  - OBJECTIVE: The aim of the present study was to evaluate the prevalence of
      metabolic syndrome in women with polycystic ovary syndrome (PCOS). SETTING:
      Infertility clinic in a tertiary care hospital. STUDY DESIGN: A prospective cross
      sectional study. MATERIALS AND METHODS: All the women attending the infertility
      clinic categorized as polycystic ovary syndrome according to Rotterdam criteria
      (2003) during the study period were included in the study. The women with PCOS
      underwent screening for metabolic syndrome as defined by the modified American
      Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) modified ATP
      111 (2005) definition. A multivariate logistic regression analysis was applied
      and significant predictors identified for the prediction of metabolic syndrome.
      RESULTS: The overall prevalence of metabolic syndrome according to the modified
      AHA/NHLBI ATP III (2005) criteria was 37.5%. A total of 5.8 % cases were detected
      to have diabetes mellitus, 8.3% had impaired fasting glucose, and 11.7 % had an
      impaired glucose test. Dyslipidemia was present in 93.3% cases of PCOS. Among all
      the risk factors, age and waist hip ratio >=0.85 were strongly associated with
      the presence of metabolic syndrome. CONCLUSION: Infertile women with PCOS,
      particularly those with age >=25 years or with central obesity (a waist hip ratio
      of >=0.85), are at a higher risk of developing metabolic syndrome and should be
      offered screening tests.

PMID- 22870012
TI  - Prediction of ovarian hyperstimulation syndrome in coasted patients in an
      IVF/ICSI program.
AB  - AIM: To determine why a subgroup of coasted patients developed moderate/severe
      ovarian hyperstimulation syndrome (OHSS) in an assisted reproduction setting.
      MATERIALS AND METHODS: Retrospective study of 2948 in-vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles with
      327 patients requiring coasting. Long protocol gonadotrophin releasing hormone
      analogue (GnRH-a) regimen was used and serum estradiol (E(2)) checked when >=20
      follicles were noted on follicular tracking. Coasting was initiated when leading
      three follicles were >=15mm with E(2) >=1635pg/ml. RESULTS: The incidence of
      moderate/severe OHSS was 10.4% in coasted patients (equivalent 1.15% of the total
      IVF/ICSI cycles in the Center). Coasted patients who subsequently developed OHSS
      showed a significantly higher number of retrieved oocytes, higher serum E(2)
      level on the day of human chorionic gonadotrophin (hCG) administration, and
      multiple pregnancies. No significant differences were noted with female age, BMI,
      cause of infertility, gonadotrophin dosage, coasting duration, and % of E(2)
      drop. CONCLUSION: Moderate/severe OHSS might be predicted in coasted patients by
      a combination of total oocyte numbers and E(2) level on the day of hCG. Multiple
      pregnancies also significantly increased the risk.

PMID- 22870013
TI  - Testicular toxicity and sperm quality following cadmium exposure in rats:
      Ameliorative potentials of Allium cepa.
AB  - AIMS: This study was carried out to investigate the effect of Allium cepa crude
      extract on cadmium-induced testicular toxicity in rats. MATERIALS AND METHODS:
      Adult male Sprague-Dawley rats were randomized into 4 groups (n = 6). Group 1 was
      used as control, group 2 was administered 0.3 mg/kgBW of cadmium sulfate
      (CdSO(4)) intraperitoneally for 3 days, group 3 was pretreated with 1 ml/100 g BW
      of Allium cepa (AcE) for 8 weeks followed by intraperitoneal administration of
      0.3 mg/kgBW of CdSO(4) in the last 3 days of experiment, and group 4 was
      administered 1 ml/100 g BW of AcE throughout the experiment. Testicular weight
      and semen analysis revealing the sperm count, sperm motility, and sperm
      morphology was carried out. Superoxide dismutase (SOD), catalase activities, and
      lipid peroxidation status were also carried out in testes. RESULTS: The study
      demonstrated that Allium cepa ameliorated CdSO(4)-induced alteration in
      testicular weight, sperm count, sperm motility, and sperm morphology. It also
      showed that Allium cepa attenuated the derangement of lipid peroxidation profile
      in testicular tissues caused by CdSO(4) exposure. CONCLUSIONS: The findings in
      the study showed that pre-treatment of rat model with Allium cepa extract
      prevented CdSO(4)-induced reproductive toxicity by improving sperm quality and
      enhancing testicular lipid peroxidation status.

PMID- 22870014
TI  - Antifertility activity of Cryptolepis sanguinolenta leaf ethanolic extract in
      male rats.
AB  - BACKGROUND: Complementary medicine has grown over time with more botanicals
      emerging and remaining integral parts of medicare. Such botanicals include
      Cryptolepis sanguinolenta. AIM: This study investigated the effect of Cryptolepis
      sanguinolenta leaf ethanolic extract on male reproductive system using rat model.
      MATERIALS AND METHODS: Control and treated rats were maintained on control diet.
      Treated rats also received graded doses of the extract. RESULTS: When compared
      with the controls, Cryptolepis sanguinolenta treatment led to significant
      testosterone suppression associated with consequent significant rise in
      luteinizing hormone (LH) and decrease in sperm count. Treatment with Cryptolepis
      sanguinolenta did not result in significant attenuation of follicular stimulating
      hormone (FSH) levels and testicular morphometry. Sperm viability, motility, and
      morphology were also comparable in all groups. CONCLUSION: These results suggest
      that Cryptolepis sanguinolenta possesses anti-androgenic and anti-spermatogenic
      properties with potential anti-aphrodisiac activity.

PMID- 22870015
TI  - Effect of noise stress on count, progressive and non-progressive sperm motility,
      body and genital organ weights of adult male rats.
AB  - AIMS: It was decided to investigate the effect of noise pollution on the body
      weight, genital organ weights, and also on sperm parameters. SETTING AND DESIGN:
      It is a prospective study designed in vitro. MATERIALS AND METHODS: A total 20
      adult male wistar rats were used in this study. All rats were divided into 2
      equal groups (n = 10): (1) control group and (2) experimental group. Animals of
      the experimental group were exposed to noise for 50 days with an intensity of 90
      120 db and frequency of 300 - 350 Hz for 12 hours daily. After 50 days, at first,
      body weights of all animals were recorded, and then they were killed. The right
      epididymides were removed and also, sperm concentration and motility were
      determined. Each organ was weighed separately on an electronic balance.
      STATISTICAL ANALYSIS USED: Data are reported as mean +/- SD and percentage. The
      statistical significance of difference between the control and experimental
      groups was determined by the unpaired t-test. RESULTS: The weights of the testes,
      epididymes, seminal vesicle, ventral prostate were found to be significantly
      decreased in rats exposed to noise pollution when compared with the weights of
      the same organs obtained from control group (P < 0.05). There was a statistical
      difference of P < 0.05 between the 2 groups in terms of sperm concentration.
      CONCLUSIONS: It is concluded that noise pollution has the bad effects on sperm
      concentration and motility; therefore, it is supposed that homes and places of
      working must be build far away of noisy of factories and other places with noise.

PMID- 22870016
TI  - MTHFR C677T polymorphism is associated with hyperlipidemia in women with
      polycystic ovary syndrome.
AB  - CONTEXT: Women with polycystic ovary syndrome (PCOS) are prone for coronary
      artery disease (CAD), and hyperhomocysteinemia is an independent risk factor for
      CAD. MTHFR deficiency is the most common cause of hyperhomocysteinemia, thereby
      provoking a possible association between PCOS and MTHFR C677T polymorphism. AIMS:
      The aim of this study was to investigate an association of MTHFR C677T
      polymorphism with PCOS. SETTINGS AND DESIGN: 92 women with PCOS (Rotterdam
      criteria) and 95 age-matched controls were compared with respect to MTHFR C677T
      polymorphism. The 2 genotypes (CC and CT) obtained were compared with clinical
      and laboratory parameters in women with PCOS. MATERIALS AND METHODS: In a case
      control study, clinical, biochemical, hormonal and genetic analysis (PCR-RFLP of
      peripheral leucocytes) was carried out on all women with PCOS as well as
      controls. STATISTICAL ANALYSIS: Student "t" test for quantitative and Chi-square
      test for nominal variables was used. For estimation of risk, odds ratio and 95%
      confidence interval were calculated. RESULTS: The odds ratio of bearing a
      heterozygous genotype (CT) was 1.32 in women with PCOS as compared to controls (P
      = 0.48). No homozygous mutation (TT) was found in the study population. Serum
      cholesterol was more in heterozygous (CT) genotype (215.48 +/- 25.56 mg/dl) as
      compared to normal (CC) genotype (203.29 +/- 16.35 mg/dl) in women with PCOS (P =
      0.01). Similarly, serum triglyceride was more in heterozygous (CT) genotype
      (95.86 +/- 37.34 mg/dl) as compared to normal (CC) genotype (82.36 +/- 20.88
      mg/dl) in women with PCOS (P = 0.04). CONCLUSIONS: Although not statistically
      significant, there is a slightly higher prevalence of heterozygous (CT) genotype
      in women with PCOS. MTHFR C677T polymorphism when present may confer an increased
      susceptibility to develop hyperlipidemia in women with PCOS. More prospective
      studies are needed to confirm whether this hyperlipidemia due to MTHFR C677T
      polymorphism clinically manifests into CAD in long term in women with PCOS.

PMID- 22870017
TI  - Successful management of heterotopic pregnancy after fetal reduction using
      potassium chloride and methotrexate.
AB  - Heterotopic pregnancy, the presence of two gestational sacs simultaneously, is a
      rare event but with the advent of Assisted Reproductive Technology, it is now an
      increasingly common complication. The reported incidence of a heterotopic
      pregnancy in a spontaneous cycle is quoted as 1 in 30,000. We report the case of
      a 38-year-old primigravida who was referred to our center at 11 + 2 weeks
      gestation with a diagnosis of heterotopic pregnancy for further management. A non
      surgical intervention comprising of transvaginal ultrasound-guided potassium
      chloride and methotrexate into the cervical pregnancy resulted in a successful
      outcome. As an obstetrician, a high index of clinical suspicion and an early scan
      is mandatory to make a diagnosis of a heterotopic pregnancy and manage
      accordingly.

PMID- 22870018
TI  - A rare case of unruptured viable secondary ovarian pregnancy after IVF/ICSI
      treated by conservative laparoscopic surgery.
AB  - Although the incidence of ectopic pregnancy is on the rise, ovarian pregnancy
      after in vitro fertilization and embryo transfer is a rare entity. Here, we
      report a case of unruptured ovarian pregnancy following in-vitro
      fertilization/intracytoplasmic sperm injection, which was treated by conservative
      laparoscopic surgery.

PMID- 22870019
TI  - "Mixed germ cell testicular tumor" in an adult female.
AB  - The androgen insensitivity (testicular feminization) syndrome was described by
      Morris in phenotypic females with 46XY karyotype, presenting with primary
      amenorrhea, adequate breast development, and absent or scanty pubic or axillary
      hair. Gonads consist usually of seminiferous tubules without spermatogenesis.
      These patients have a 5-10% risk of developing germ cell tumors, usually after
      the complete development of secondary female sexual characteristics. We hereby
      report a case considered as a female with married life of 15 years, who was
      operated for severe abdominal pain. Phenotype characters were that of female.
      Microscopic examination of the tumor from the abdomen revealed germinoma and yolk
      sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final
      diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome
      was made. Surveillance may be the most appropriate option when these conditions
      are initially diagnosed in adulthood to prevent development of germ cell tumors.

PMID- 22870020
TI  - OHVIRA: Uterus didelphys, blind hemivagina and ipsilateral renal agenesis:
      Advantage MRI.
AB  - We present here a case of an uncommon complex uterine anomaly - Obstructed
      HemiVagina with Ipsilateral Renal Agenesis (OHVIRA), also known as Herlyn-Werner
      Wunderlich syndrome in a 14-year-old girl along with sonographic (trans-abdominal
      and trans labial), and MRI findings. The patient underwent surgery wherein
      imaging findings were confirmed. An MRI has proved to be of great help in correct
      diagnosis avoiding surgical interventions/ laparoscopy, which were needed in past
      to diagnose this rare anomaly. We also discuss the development of this anomaly
      with the help of a relatively new theory of uro-genital development by Acien and
      review the literature.

PMID- 22870021
TI  - Therapeutic effect of 0.03% tacrolimus ointment for ocular graft versus host
      disease and vernal keratoconjunctivitis.
AB  - PURPOSE: To determine whether topical tacrolimus might prove effective in the
      treatment of refractory anterior segment inflammatory diseases, and to evaluate
      its efficacy in eyes with ocular graft versus host disease (GVHD), and vernal
      keratoconjunctivitis (VKC). METHODS: Twenty-eight eyes of 14 patients with
      anterior segment inflammation refractory to steroid treatment were treated with
      0.03% tacrolimus ointment at the Samsung Medical Center, Seoul, Korea from March
      2008 through August 2009. Seven patients had ocular GVHD and seven had VKC. We
      evaluated the conjunctival and corneal inflammatory change at one, two, four, and
      eight weeks after treatment with a scoring system. Time to initial response of
      treatment and therapeutic effect between GVHD and VKC was also analyzed. After
      the eight-week treatment period, patients were divided into two groups
      (maintenance group and discontinuance group). Eight patients maintained the
      treatment for an additional four months, and six patients discontinued the
      treatments. Therapeutic effect was also compared between the groups at eight
      weeks and six months after treatment. RESULTS: The mean conjunctival and corneal
      inflammation score was reduced significantly at eight weeks after treatment (p <
      0.0001). The therapeutic effect in conjunctival inflammation was first noted at
      week two after the initial treatment (p = 0.002); reduction in corneal
      inflammation was first noted at one week (p = 0.0009). When compared according to
      diagnosis, no therapeutic difference was detected between the groups (p > 0.05).
      Six months after treatment, we noted no therapeutic differences between the
      maintenance group and discontinuance group (p > 0.05). CONCLUSIONS: 0.03%
      tacrolimus ointment was safe and effective for use in anterior segment
      inflammatory disease refractory to steroid.

PMID- 22870022
TI  - A potential role of crystallin in the vitreous bodies of rats after ischemia
      reperfusion injury.
AB  - PURPOSE: Ischemia-reperfusion injury (I/R injury) is known not only to induce
      hypoxic and oxidative stress, but also to cause retinal degeneration in rats.
      Crystallins, known to inhibit the formation of reactive oxygen species, reduce
      apoptotic cell death. Our goal was to clarify not only the role of I/R injury
      mediated crystallins, but also to evaluate the correlation of these compounds to
      anti-inflammation in the vitreous body. METHODS: Twenty-four Sprague-Dawley rats
      were used in this study. We induced I/R injury by clamping the optic nerve for 30
      minutes and then releasing it. The vitreous bodies were obtained from the
      experimental and control subjects 24, 48, and 72 hours after I/R injury. Two
      dimensional electrophoresis was performed, and the targeted spots were further
      investigated using matrix-assisted laser desorption-ionization time-of-flight
      mass spectrometry, spectrophotometry, Western blotting, and histological
      examination. RESULTS: After I/R injury, 23 spots were identified as crystallins.
      The betaB2 crystallins were transcriptionally and post-translationally regulated,
      whereas the alphaB crystallins were controlled by post-translational
      modifications in the vitreous bodies of the rats. The total amounts of alphaA and
      beta crystallins (including isotypes of beta crystalline) had increased 48 hours
      after injury. The phosphorylation of alphaB crystallin (at serine residues 19,
      45, and 59) was significantly increased 48 hours later, whereas phosphorylation
      of ERK1/2 showed the greatest decrease. CONCLUSIONS: During hypoxic and oxidation
      stress, our results suggest that phosphorylated alphaB crystalline inhibits RAS,
      resulting in the inactivation of ERK1/2. The phosphorylation of alphaB crystallin
      may be associated with the inflammatory suppression in the vitreous body via the
      I/R injury model system.

PMID- 22870023
TI  - Measurement of choroidal thickness in normal eyes using 3D OCT-1000 spectral
      domain optical coherence tomography.
AB  - PURPOSE: To study choroidal thickness and its topographic profile in normal eyes
      using 3D OCT-1000 spectral domain optical coherence tomography and the
      correlation with age and refractive error. METHODS: Fifty-seven eyes (45
      individuals) with no visual complaints or ocular disease underwent horizontal and
      vertical line scanning using 3D OCT-1000. The definition of choroidal thickness
      was the vertical distance between the posterior edge of the hyper-reflective
      retinal pigment epithelium and the choroid/sclera junction. Choroidal thickness
      was measured in the subfoveal area at 500 um intervals from the fovea to 2,500 um
      in the nasal, temporal, superior, and inferior regions. The spherical equivalent
      refractive error was measured by autorefractometry. Statistical analysis was used
      to confirm the correlations of choroidal thickness with age and refraction error.
      RESULTS: The mean age of the 45 participants (57 eyes) was 45.28 years. Detailed
      visualization of the choroid for measuring its thickness was possible in 63.3% of
      eyes. The mean subfoveal choroidal thickness was found to be 270.8 um (standard
      deviation [SD], +/-51 um), in horizontal scanning and 275.0 um (SD, +/-49 um) in
      vertical scanning. The temporal choroidal thickness was greater than any 500 um
      interval in corresponding locations, and there was no significant difference
      between the superior and inferior choroid as far as 2,000 um from the fovea. Age
      and refractive error were associated with subfoveal choroidal thickness in terms
      of regression (p < 0.05). CONCLUSIONS: Choroidal thickness in normal Korean eyes
      can be measured using 3D OCT-1000 with high resolution line scanning. The
      topographical profile of choroidal thickness varies depending on its location.
      Age and refractive error are essential factors for interpretation of choroidal
      thickness.

PMID- 22870024
TI  - Systemic factors associated with central serous chorioretinopathy in Koreans.
AB  - PURPOSE: To investigate systemic factors associated with central serous
      chorioretinopathy (CSC). METHODS: We retrospectively reviewed the medical records
      of 113 Korean patients who were diagnosed with CSC and who underwent history
      taking with a specialized questionnaire for CSC. They were matched for age and
      gender at a ratio of 1 : 3 to 339 normal controls. Normal controls were
      consecutively selected from a database at the Health Promotion Center. General
      characteristics and medical histories were compared between the two groups. The
      statistical analyses used included independent t-test, Mann-Whitney test,
      Fisher's exact test, and multivariate logistic regression analysis. RESULTS:
      There were 90 men and 23 women in the CSC group, and the male-female ratio for
      both groups was 3.9 : 1. The mean age of the patients was 45.6 years. In
      multivariate analysis, hypertension (odds ratio [OR], 2.327; 95% confidence
      interval [CI], 1.349-4.013), use of medicinal plants (OR, 2.198; 95% CI, 1.193
      4.049), sleep disturbances (OR, 1.732; 95% CI, 1.096-2.739), and snoring (OR,
      1.727; 95% CI, 1.058-2.820) were strongly associated with CSC. CONCLUSIONS:
      Hypertension, sleep disturbance, snoring, and medicinal plant use were identified
      as factors associated with CSC. Expanded history taking, including systemic
      factors and culture-specific behavior related to stress or fatigue such as use of
      medicinal plants, will be helpful in identifying Korean patients at an increased
      risk for CSC.

PMID- 22870025
TI  - Comparative study of encapsulated blebs following Ahmed glaucoma valve
      implantation and trabeculectomy with mitomycin-C.
AB  - PURPOSE: To compare the histopathologic and morphologic findings of encapsulated
      blebs following Ahmed glaucoma valve implantation and primary standard
      trabeculectomy with mitomycin-C. METHODS: We reviewed the records of patients
      with otherwise uncontrollable glaucoma who had undergone Ahmed glaucoma valve
      implantation or trabeculectomy with mitomycin-C. Five eyes that underwent Ahmed
      valve implantation and three eyes that underwent trabeculectomy needed surgical
      revision of the initial surgery due to encapsulated bleb development with total
      loss of function. The surgically removed encapsulated blebs were analyzed
      macroscopically and microscopically. RESULTS: Removal of the encapsulated bleb
      was performed at a mean follow-up time of 26.6 +/- 19.4 weeks in the Ahmed valve
      implantation group and 12.0 +/- 11.4 weeks in the trabeculectomy group. The
      fibrotic wall of the encapsulated blebs had an overall thickness of 2.48 +/- 0.42
      mm in the Ahmed valve implantation group and 1.62 +/- 0.37 mm in the
      trabeculectomy group. Macroscopically, the coconut flesh-like smooth surface was
      split into two layers, and the wall of the capsule was thicker in the Ahmed valve
      implantation group than in the trabeculectomy group. Histopathologically, the
      fibrotic capsule was composed of an inner fibrodegenerative layer and an outer
      fibrovascular layer, and there were no histopathological differences between the
      two groups. CONCLUSIONS: The fibrotic capsule wall was thicker in the Ahmed valve
      group, but there were no differences in histological findings between the two
      groups.

PMID- 22870026
TI  - The effect of axial length on the variability of Stratus optical coherence
      tomography.
AB  - PURPOSE: To evaluate the effect of axial length on the variability of retinal
      nerve fiber layer (RNFL) thickness measurements using the Stratus optical
      coherence tomography (OCT) in normal and glaucomatous eyes. METHODS: We measured
      the RNFL thickness in 474 subjects using the Stratus OCT twice during the same
      day. Axial length was measured with the IOLMaster, and refractive error was the
      absolute value of the spherical equivalent measured with an auto ref-keratometer.
      Standard deviation in overall mean RNFL thickness was used as the dependent
      variable to identify significant correlations. RESULTS: Long axial length
      affected the variability in the RNFL thickness value by stratus OCT at the
      temporal quadrant (p = 0.006) and clock-hour sector 9 (p = 0.001). Refractive
      error also affected the variability of the RNFL thickness value by stratus OCT at
      the temporal quadrant (p = 0.025) and clock-hour sector 9 (p = 0.024).
      CONCLUSIONS: It is clinically significant that longer axial length demonstrates
      greater variability in temporal area as detected by OCT, a measurement which
      correlates with the preferably damaged position in the myopic glaucoma eye.

PMID- 22870027
TI  - Long-term results of lens-sparing vitrectomy for progressive posterior-type stage
      4A retinopathy of prematurity.
AB  - PURPOSE: To assess the long-term anatomic and visual outcomes and associated
      complications of lens-sparing vitrectomy (LSV) in infants with progressive
      posterior-type tractional retinal detachment (TRD) associated with stage 4A
      retinopathy of prematurity (ROP). METHODS: In a retrospective case series, the
      medical records of consecutive patients who presented with progressive posterior
      type stage 4A ROP and underwent LSV between 1999 and 2007 were reviewed. Retinal
      attachment status, visual acuity, and development of postoperative complications
      were assessed. RESULTS: Eleven eyes of 9 patients were included. The mean follow
      up period was 4.6 years. In 8 eyes (73%), plus disease was present at the time of
      LSV. In 3 eyes (27%), 2 (66%) without plus disease and 1 (13%) with plus disease,
      the retina remained reattached in the end, while 8 eyes (73%) had TRD on final
      examination. Two eyes with reattached retinas showed favorable visual acuity. In
      those eyes with detached retinas, 5 (68%) showed no light perception. When
      surgery for ROP was unsuccessful, development of cataract, corneal opacity, or
      glaucoma was common. CONCLUSIONS: The long-term anatomic success rate of LSV for
      progressive posterior-type stage 4A ROP was low, especially in the presence of
      plus disease at the time of LSV. Anatomical reattachment is very important for
      preventing complications and gaining better visual outcomes.

PMID- 22870028
TI  - Superior rectus muscle recession for residual head tilt after inferior oblique
      muscle weakening in superior oblique palsy.
AB  - PURPOSE: Residual head tilt has been reported in patients with superior oblique
      muscle palsy (SOP) after surgery to weaken the inferior oblique (IO) muscle. The
      treatments for these patients have not received appropriate attention. In this
      study, we evaluated the superior rectus (SR) muscle recession as a surgical
      treatment. METHODS: The medical records of 12 patients with SOP were
      retrospectively reviewed. Each of these patients had unilateral SR muscle
      recession for residual head tilt after IO muscle weakening due to SOP. The
      residual torticollis was classified into three groups on the basis of severity:
      mild, moderate, or severe. Both IO muscle overaction and vertical deviation,
      features of SOP, were evaluated in all patients. The severity of the preoperative
      and postoperative torticollis and vertical deviation were compared using a paired
      t-test and Fisher's exact test. RESULTS: The torticollis improved in nine of 12
      (75%) patients after SR muscle recession. The difference between the preoperative
      and postoperative severity of torticollis was statistically significant (p =
      0.0008). After surgery, the mean vertical deviation was significantly reduced
      from 12.4 prism diopters to 1.3 prism diopters (p = 0.0003). CONCLUSIONS:
      Unilateral SR muscle recession is an effective method to correct residual head
      tilt after IO muscle weakening in patients with SOP. This surgical procedure is
      believed to decrease head tilt by reducing the vertical deviation and thereby the
      compensatory head tilt.

PMID- 22870029
TI  - Safety of bevacizumab on extraocular muscle in a rabbit model.
AB  - PURPOSE: The purpose of this study was to investigate the myotoxicity of
      bevacizumab on extraocular muscles in a rabbit model. METHODS: Thirty New Zealand
      white rabbits were used for this study. The animals were evenly divided into two
      groups. In the first group, 15 rabbits were treated with intramuscular injections
      of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal
      saline solution (0.05 mL) in the left superior rectus muscle. In the second
      group, 15 rabbits were treated with subconjunctival injections of bevacizumab
      (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline
      solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each
      group were sacrificed at one day, two weeks and four weeks after the injections.
      Extraocular muscle samples were prepared for light microscopic (LM) and electron
      microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD
      11b immunohistochemistry, and global muscle change was investigated using
      hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson
      trichrome stains, and ultrastructural changes were observed on EM. RESULTS: We
      observed no significant inflammatory cell infiltration, muscle necrosis or
      fibrotic change in treated and control eyes. EM findings revealed no significant
      damage to muscle or vascular tissue after bevacizumab injection. CONCLUSIONS: We
      found no signs of extraocular muscle toxicity after LM and EM intramuscular and
      subconjunctival bevacizumab injections in a rabbit model.

PMID- 22870030
TI  - Multilobular lacrimal sac diverticulum presenting as a lower eyelid mass.
AB  - Lacrimal sac diverticulum is a rare condition, and its various symptoms
      complicate differential diagnosis. We present cases of a peculiar type of
      lacrimal diverticulum. A 5-year-old girl and a 50-year-old woman presented with a
      protruding mass inferior to the medial canthus. Each lacrimal system was patent
      to irrigation. The masses compressed and distorted the lacrimal passage and had
      no apparent connection with the lacrimal sac in dacryocystography or computed
      tomography. Surgical exploration and complete excision of the masses were
      completed. Each patient had an inverted Y- and an inverted V-shaped multilobular
      cystic mass that was pathologically confirmed as a lacrimal sac diverticulum.
      Lacrimal sac diverticula may rarely take the form of a multilobular cyst and can
      present as a lower lid mass. We speculate that an abnormality in lacrimal
      embryogenesis resulted in multiple blind pouches, a peculiar type of lacrimal sac
      diverticulum.

PMID- 22870031
TI  - A novel decorin gene mutation in congenital hereditary stromal dystrophy: a
      Korean family.
AB  - A 43-year-old man developed decreased vision in the right eye that had persisted
      for seven years. Under slit lamp examination, corneal clouding was noted with
      normal endothelium and ocular structure. From the clinical evidence, we suspected
      that the patient had congenital hereditary stromal dystrophy (CHSD). He and his
      family underwent a genetic analysis. Penetrating keratoplasty was conducted, and
      the corneal button was investigated for histopathologic confirmation via both
      light and electron microscopy. The histopathologic results revealed mildly
      loosened stromal structures, which exhibited an almost normal arrangement and
      differed slightly from the previous findings of CHSD cases. With regard to the
      genetic aspects, the patient and his mother harbored a novel point mutation of
      the decorin gene. This genetic mutation is also distinct from previously
      described deletion mutations of the decorin gene. This case involved delayed
      penetration of mild clinical symptoms with the histological feature of a loosened
      fiber arrangement in the corneal stroma. We concluded that this condition was a
      mild form of CHSD. However, from another perspective, this case could be
      considered as "decorin gene-associated corneal dystrophy," which is distinct from
      CHSD. Further evaluation will be required for appropriate clinical,
      histopathologic and genetic approaches for such cases.

PMID- 22870032
TI  - A case of postoperative endophthalmitis by extended-spectrum beta-lactamase
      producing Escherichia coli.
AB  - A 75-year-old female was transferred to our clinic three days after uneventful
      phacoemulsification with intraocular lens (IOL) implantation in the right eye
      that had been carried out at a local clinic. Under the diagnosis of postoperative
      endophthalmitis, the patient underwent pars plans vitrectomy, IOL explantation,
      silicone oil tamponade, and intravitreal antibiotic injection. Even after the
      procedure, the patient's condition was further aggravated, and extended-spectrum
      beta-lactamase-producing Escherichia coli were identified on bacterial
      identification test. Although meropenem was applied locally and systemically, the
      patient had no-light perception visual acuity.

PMID- 22870033
TI  - Recurrent bilateral retinal vasculitis as a manifestation of post-streptococcal
      uveitis syndrome.
AB  - We report a case of post-streptococcal uveitis mainly presenting with bilateral
      recurrent retinal vasculitis in Korea. A 14-year-old Asian female presented with
      decreased visual acuity of 20 / 30 in the right eye and 20 / 25 in the left eye.
      The patient had a history of glomerulonephritis nine months before onset of
      uveitis. The manifestation of uveitis was predominantly retinal vasculitis. We
      presumed post-streptococcal uveitis because probable streptococcal infection was
      confirmed by anti-streptolysin O titer elevation. With topical and oral steroid
      treatments, the patient experienced complete vision recovery. Post-streptococcal
      uveitis occurs rarely and mostly involves young patients in the form of non
      granulomatous anterior uveitis. However, as this case shows, it may primarily
      involve the posterior uvea without anterior inflammation and may recur.

PMID- 22870034
TI  - Resolution of macular edema after systemic treatment with furosemide.
AB  - We report two cases of macular edema treated with the oral administration of
      furosemide. The first case presented here was a 78-year-old male patient with
      visual disturbance of the left eye. He had been taking an oral agent for diabetes
      and had chronic renal failure for 7 years. From 10 days prior to the visit, he
      had visual disturbance of the left eye accompanied by systemic edema. There were
      no specific findings in the anterior segment, but sub-retinal fluid was observed
      in the left fundus. Macular edema was observed on fluorescein angiography and
      optical coherence tomography; therefore, the oral administration of furosemide
      was initiated. After seven days, the sub-retinal fluid disappeared. The second
      case was a 43-year-old female patient with visual disturbance of the left eye who
      had been taking hypoglycemic agents for diabetes for 13 years. There were no
      specific findings in the anterior segment, but flame-shaped retinal hemorrhages
      were scattered over both posterior poles, neovascularization was observed in the
      left eye, and, of particular note, sub-retinal fluid was detected in the macula
      of the left eye. Macular edema was also observed on fluorescein angiography and
      optical coherence tomography, and oral administration of furosemide was
      initiated. After 3 weeks, the macular edema had significantly decreased.

PMID- 22870035
TI  - Congenital ocular anomaly in an infant with trisomy 14 mosaicism.
AB  - Trisomy 14 mosaicism is a rare chromosomal abnormality with distinct and
      recognizable clinical features. We report a patient with presumed retinal
      dystrophy having diffuse retinal pigment epithelial abnormalities, which has not
      been previously reported in association with trisomy 14. This case expands the
      clinical spectrum of this rare entity.

PMID- 22870036
TI  - Proof of concept in cardiovascular risk: the paradoxical findings in blood
      pressure and lipid abnormalities.
AB  - High blood pressure and lipoprotein abnormalities were identified by many cohort
      studies as the major risk factors for cardiovascular disease. Laboratory
      experiments apparently confirmed their role in the causation of atherosclerosis,
      but a proof of concept requires the corroboration by clinical trials in human
      beings. The size of benefit in clinical trials regarding the control of high
      blood pressure was within the estimations of risk provided by cohort studies. For
      a reduction of 10 mmHg in systolic blood pressure or 5 mmHg in diastolic blood
      pressure, the relative risk reduction of coronary heart disease was 22% (95%
      confidence interval 27%-17%) in a meta-analysis of clinical trials, close to the
      estimation of reduction of 25% (95% confidence interval 23%-27%) provided by a
      meta-analysis of cohort studies. The corresponding values for stroke were 41%
      (95% confidence interval 33%-48%) in clinical trials compared to a cohort risk
      prediction of 36% (95% confidence interval 34%-38%). This efficacy was shared by
      all blood pressure-lowering drugs. The same figure has not paradoxically happened
      with drugs that act over abnormalities of cholesterol and lipoproteins. Only
      statins, which have other beneficial actions as well, have consistently lowered
      the incidence of cardiovascular diseases, an efficacy that was not reproduced by
      older and newer quite potent lipid drugs. The adverse effects of these drugs may
      nullify their beneficial effects over lipoproteins and abnormalities of
      lipoproteins may only be surrogate markers of the underlying real risks.

PMID- 22870038
TI  - Treatment of advanced pancreatic neuroendocrine tumors: potential role of
      everolimus.
AB  - Pancreatic neuroendocrine tumors (PanNETs) are frequently diagnosed at
      unresectable stage and remain a medical challenge. Everolimus (RAD001,
      Afinitor((r)), Novartis, Basel, Switzerland), an orally administered inhibitor of
      mammalian target of rapamycin (mTOR), was recently approved by the Food and Drug
      Administration to treat patients with advanced PanNETs. This review will examine
      the mechanism of action of everolimus, the function of mTOR and its inhibition,
      PanNETs and the mTOR pathway, and clinical trials of everolimus in PanNETs.
      Future investigations will focus on everolimus combination therapy to treat
      PanNETs and the discovery of predictive biomarkers for response to everolimus.

PMID- 22870039
TI  - Treatment of dengue fever.
AB  - The endemic area for dengue fever extends over 60 countries, and approximately
      2.5 billion people are at risk of infection. The incidence of dengue has
      multiplied many times over the last five decades at an alarming rate. In the
      endemic areas, waves of infection occur in epidemics, with thousands of
      individuals affected, creating a huge burden on the limited resources of a
      country's health care system. While the illness passes off as a simple febrile
      episode in many, a few have a severe illness marked by hypovolemic shock and
      bleeding. Iatrogenic fluid overload in the management may further complicate the
      picture. In this severe form dengue can be fatal. Tackling the burden of dengue
      is impeded by several issues, including a lack of understanding about the exact
      pathophysiology of the infection, inability to successfully control the vector
      population, lack of specific therapy against the virus, and the technical
      difficulties in developing a vaccine. This review provides an overview on the
      epidemiology, natural history, management strategies, and future directions for
      research on dengue, including the potential for development of a vaccine.

PMID- 22870040
TI  - Economic evaluation of bevacizumab in the treatment of non-small cell lung cancer
      (NSCLC).
AB  - BACKGROUND: Delivering affordable cancer care is becoming increasingly important.
      Bevacizumab (BEV) is a costly molecular targeted agent effective for a variety of
      cancer including lung cancer. The objective of this review is to assess published
      economic evaluation of BEV in the treatment of non-small cell lung cancer
      (NSCLC). METHODS: A literature search in PubMed, Cochrane, and the Health
      Technology Assessment reports for English-language publications before February
      2012 was performed. Studies were independently screened by two reviewers, and
      eight publications were included in the review. The results of these eight
      articles were tabulated and all cost estimates were reported in 2011 US dollars.
      RESULTS: Among the eight articles, three were cost studies and five were cost
      effectiveness/utility analysis. For first-line treatment, BEV-containing regimen
      was reported to be the most costly regimen in one study but cost saving when
      compared with pemetrexed/cisplatin in another study. When compared with other
      regimens, BEV-containing regimen was reported to be cost effective in two cost
      effectiveness studies (incremental cost-effectiveness ratio [ICER] in the range
      of US$30,318-US$54,317 per life year) but not cost effective in the other three
      studies (ICER over US$300,000 per life year). CONCLUSION: In this review of
      economic evaluation of BEV in the treatment of NSCLC, it was found that the
      literature was not conclusive on the economic benefit of BEV. The role of BEV in
      other treatment settings for NSCLC was unknown. Further studies, such as clinical
      trials with adequate power to compare the efficacy between low dose and high dose
      BEV, potential impact of predictive biomarkers for BEV, and comprehensive
      economic evaluation will strengthen the current state of knowledge on the
      economic value of BEV in NSCLC.

PMID- 22870041
TI  - The geography of HIV/AIDS prevalence rates in Botswana.
AB  - BACKGROUND: Botswana has the second-highest human immunodeficiency virus (HIV)
      infection rate in the world, with one in three adults infected. However, there is
      significant geographic variation at the district level and HIV prevalence is
      heterogeneous with the highest prevalence recorded in Selebi-Phikwe and North
      East. There is a lack of age-and location-adjusted prevalence maps that could be
      used for targeting HIV educational programs and efficient allocation of resources
      to higher risk groups. METHODS: We used a nationally representative household
      survey to investigate and explain district level inequalities in HIV rates. A
      Bayesian geoadditive mixed model based on Markov Chain Monte Carlo techniques was
      applied to map the geographic distribution of HIV prevalence in the 26 districts,
      accounting simultaneously for individual, household, and area factors using the
      2008 Botswana HIV Impact Survey. RESULTS: Overall, HIV prevalence was 17.6%,
      which was higher among females (20.4%) than males (14.3%). HIV prevalence was
      higher in cities and towns (20.3%) than in urban villages and rural areas (16.6%
      and 16.9%, respectively). We also observed an inverse U-shape association between
      age and prevalence of HIV, which had a different pattern in males and females.
      HIV prevalence was lowest among those aged 24 years or less and HIV affected over
      a third of those aged 25-35 years, before reaching a peak among the 36-49-year
      age group, after which the rate of HIV infection decreased by more than half
      among those aged 50 years and over. In a multivariate analysis, there was a
      statistically significant higher likelihood of HIV among females compared with
      males, and in clerical workers compared with professionals. The district-specific
      net spatial effects of HIV indicated a significantly higher HIV rate of 66%
      (posterior odds ratio of 1.66) in the northeast districts (Selebi-Phikwe, Sowa,
      and Francistown) and a reduced rate of 27% (posterior odds ratio of 0.73) in
      Kgalagadi North and Kweneng West districts. CONCLUSION: This study showed a clear
      geographic distribution of the HIV epidemic, with the highest prevalence in the
      east-central districts. This study provides age- and location-adjusted prevalence
      maps that could be used for the targeting of HIV educational programs and
      efficient allocation of resources to higher risk groups. There is need for
      further research to determine the social, cultural, economic, behavioral, and
      other distal factors that might explain the high infection rates in some of the
      high-risk areas in Botswana.

PMID- 22870042
TI  - Patient preferences for chemotherapies used in breast cancer.
AB  - BACKGROUND: Therapies for invasive breast cancer may be associated with an
      incremental survival advantage that should be weighed against the risk of
      toxicities when making treatment decisions. The objective of this study was to
      elicit patient preferences for a comprehensive profile of attributes associated
      with chemotherapies for breast cancer. METHODS: This was a cross-sectional study
      of 121 patients with stage I-IV breast cancer who completed an internet-based
      conjoint survey that assessed the following attributes: ten grade III/IV
      toxicities, survival advantage, and administration regimen. Literature and expert
      input were used to identify descriptions for each attribute and respective levels
      (eg, different risks of toxicities). Subjects rated the attribute levels on a
      series of scales and indicated preferences in pair-wise comparisons of two
      hypothetical treatments differing in attribute levels. Ordinary least-squares
      regression was used to calculate utilities (preference weights) for each
      attribute level. RESULTS: Of the twelve attributes, survival was the most
      important; specifically, a survival advantage of 3 months versus no survival
      advantage was most influential in the perceived value of chemotherapy. Among
      toxicities, the differences in the risks of neutropenia with hospitalization,
      diarrhea, nausea, and fatigue had the most impact on preferences; the risk
      differences of myalgia, stomatitis, and hand-foot syndrome had the least. In
      general, a more convenient administration regimen was less important than a 13%
      chance or more of severe toxicities, but more important than a 10%-12% chance of
      severe toxicities. CONCLUSION: Breast cancer patients place high value on small
      incremental survival advantages associated with treatment despite the risk of
      serious toxicities.

PMID- 22870043
TI  - Effect of high parity on occurrence of some fetal growth indices: a cohort study.
AB  - The objective of this retrospective cohort study was to explore the potential
      causal relation between parity and fetal growth indices, including low birth
      weight (LBW), macrosomia, and prematurity. The study was nested on a community
      trial in a city in Oman. The study analyzed 1939 pregnancies among 479
      participants. Of these, 944 pregnancies (48.7%) were high parity (>=5). Obtained
      newborns with outcomes of interest were as follows: 191 LBW, 34 macrosomic, and
      69 premature. Associations were measured using multilevel logistic regression
      modeling. Compared to low parity (LP, defined as <5), high parity was found to be
      associated with less risk of LBW (relative risk [RR] = 0.76; 95% confidence
      interval [CI]: 0.44-1.1) and prematurity (RR = 0.82; 95% CI: 0.54-1.27), but
      greater risk of macrosomia (RR = 1.8; 95% CI: 1.2-2.4). This study provides
      evidence that with increasing parity, risks of LBW and prematurity decrease,
      while risk of macrosomia increases.

PMID- 22870044
TI  - Differences in reporting of maternal and child health indicators: A comparison
      between routine and survey data in Guizhou Province, China.
AB  - BACKGROUND: The quality of routine data, such as the maternal mortality ratio
      (MMR), infant mortality rate (IMR), and under-five mortality rate (U5MR) is often
      questioned. The objective of this study was to compare routine and survey data on
      key maternal and child health indicators, including the MMR, IMR, and U5MR in the
      Guizhou Province of China. METHODS: In 2008, an urban area and a rural area in
      the Guizhou Province were randomly selected. All households in the selected areas
      were included and, of the total 5466 households therein, 5459 were visited. The
      response rate was 99.9%. Survey data were collected from mothers (46.0%), fathers
      (32.5%), grandmothers (11.1%), grandfathers (9.0%), and other caregivers (1.4%).
      Data from routine records of the health bureaus in selected areas were reviewed
      for the same indicators. The Chi-square test was used to study the differences
      between routine data and survey data. RESULTS: We found the differences between
      the routine and survey data live births in the survey data (68) was fewer than in
      the routine data (94) in the rural area, while live births in the survey data
      (106) was larger than in the routine data (96) in the urban area. The IMR was
      higher in the survey data (51.7 per thousand) as compared with routine data (31.6
      per thousand). The U5MR was higher (69.0 per thousand) in the survey data than in
      the routine data (42.1 per thousand). Indicators related to the coverage of
      maternal and child health interventions were over-reported in routine data.
      CONCLUSION: Small differences were observed between routine data and survey data
      in Guizhou, one of the poorest areas of China. The quality of routine data in
      urban areas was better than in rural areas.

PMID- 22870045
TI  - Treatment options for vasomotor symptoms in menopause: focus on desvenlafaxine.
AB  - Vasomotor symptoms (VMS), including hot flashes and night sweats, occur in as
      many as 68.5% of women as a result of menopause. While the median duration of
      these symptoms is 4 years, approximately 10% of women continue to experience VMS
      as many as 12 years after their final menstrual period. As such, VMS have a
      significant impact on the quality of life and overall physical health of women
      experiencing VMS, leading to their pursuance of treatment to alleviate these
      symptoms. Management of VMS includes lifestyle modifications, some herbal and
      vitamin supplements, hormonal therapies including estrogen and tibolone, and
      nonhormonal therapies including clonidine, gabapentin, and some of the serotonin
      and serotonin-norepinephrine reuptake inhibitors. The latter agents, including
      desvenlafaxine, have been the focus of increased research as more is discovered
      about the roles of serotonin and norepinephrine in the thermoregulatory control
      system. This review will include an overview of VMS as they relate to menopause.
      It will discuss the risk factors for VMS as well as the proposed pathophysiology
      behind their occurrence. The variety of treatment options for VMS will be
      discussed. Focus will be given to the role of desvenlafaxine as a treatment
      option for VMS management.

PMID- 22870046
TI  - Health complications of female genital mutilation in Sierra Leone.
AB  - Sierra Leone has one of the highest rates of female genital mutilation (FGM) in
      the world, and yet little is known about the health consequences of the practice.
      PURPOSE: To explore whether and what kind of FGM-related health complications
      girls and women in Sierra Leone experience, and to elucidate their health care
      seeking behaviors. PATIENTS AND METHODS: A feasibility study was conducted to
      test and refine questionnaires and methods used for this study. Thereafter, a
      cross-section of girls and women (n = 258) attending antenatal care and Well
      Women Clinics in Bo Town, Bo District, in the southern region and in Makeni Town,
      Bombali District, in the northern region of Sierra Leone were randomly selected.
      Participants answered interview-administrated pretested structured questionnaires
      with open- ended-questions, administrated by trained female personnel. RESULTS:
      All respondents had undergone FGM, most between 10 and 14 years of age.
      Complications were reported by 218 respondents (84.5%), the most common ones
      being excessive bleeding, delay in or incomplete healing, and tenderness. Fever
      was significantly more often reported by girls who had undergone FGM before 10
      years of age compared with those who had undergone the procedure later. Out of
      those who reported complications, 187 (85.8%) sought treatment, with 89 of them
      visiting a traditional healer, 75 a Sowei (traditional circumciser), and 16 a
      health professional. CONCLUSION: The high prevalence rate of FGM and the
      proportion of medical complications show that FGM is a matter for public health
      concern in Sierra Leone. Girls who undergo FGM before 10 years of age seem to be
      more vulnerable to serious complications than those who are older at the time of
      FGM. It is important that health care personnel are aware of, and look for
      possible complications from FGM, and encourage girls and women to seek medical
      care for their problems.

PMID- 22870047
TI  - Influence of breastfeeding on maternal blood pressure at one month postpartum.
AB  - BACKGROUND: The benefits of breastfeeding for improved health and developmental
      outcomes in mothers and their infants have been widely recognized. The purpose of
      the present study was to assess whether feeding modes influence maternal blood
      pressure at one month postpartum. METHODS: The pregnancy charts of 407 women who
      delivered at a birthing center in rural Japan between August 1998 and September
      2007 were analyzed. The criteria for inclusion were low-risk, full-term pregnancy
      (duration, 37-42 weeks) resulting in spontaneous vaginal deliveries, intrapartum
      hemorrhage < 500 mL, and a healthy infant (Apgar score >= 8 at one minute).
      RESULTS: The subjects were classified into three groups based on feeding modes.
      The proportion of each mode was 28.3% in the breastfeeding group, 56.5% in the
      mixed-feeding group, and 15.2% in the formula-feeding group. The systolic blood
      pressure (SBP) in mothers at one month postpartum for each feeding mode was 118.4
      +/- 8.7 mmHg in the breastfeeding group, 120.6 +/- 9.3 mmHg in the mixed-feeding
      group, and 122.0 +/- 9.9 mmHg in the formula-feeding group. SBP at one month
      postpartum in the breastfeeding group was significantly lower than that in the
      other groups. No significant differences were observed in diastolic blood
      pressure in the three groups at one month postpartum. CONCLUSION: Breastfeeding
      resulted in lower SBP in mothers at one month postpartum compared with those
      using other feeding modes, thus indicating an effect of breastfeeding on maternal
      blood pressure.

PMID- 22870048
TI  - Molecular and Morphological Characterization of Endophytic Heterobasidion
      araucariae from Roots of Capsicum annuum L. in Korea.
AB  - A species of Heterobasidion was encountered during a diversity study of
      endophytic fungi from healthy root tissues of chili pepper (Capsicum annuum L.)
      in Korea. The fungal species (CNU081069) was identified as Heterobasidion
      araucariae based on phylogenetic analyses of the internal transcribed spacer and
      translation elongation factor gene sequences. Morphological descriptions of the
      endophytic isolate matched well with the previous references and supported the
      molecular identification. The fungus Heterobasidion araucariae CNU081069 is new
      to Korea.

PMID- 22870049
TI  - A new record of the genus mycobilimbia (ramalinaceae) from South Korea.
AB  - The study introduces the genus Mycobilimbia, from South Korea. M. philippina is
      reported here as being new to the country. Characteristic features of the species
      are crustose thallus, globose apothecia, K-proper exciple and hypothecium,
      Biatora-type asci, 3-septate fusiform ascospores, and a lack of secondary
      compounds.

PMID- 22870050
TI  - Mariannaea samuelsii Isolated from a Bark Beetle-Infested Elm Tree in Korea.
AB  - During an investigation of fungi from an elm tree infested with bark beetles in
      Korea, one isolate, DUCC401, was isolated from elm wood. Based on morphological
      characteristics and phylogenetic analysis of the internal transcribed spacer and
      28S rDNA (large subunit) sequences, the isolate, DUCC401, was identified as
      Mariannaea samuelsii. Mycelia of the fungus grew faster on malt extract agar than
      on potato dextrose agar and oatmeal agar media. Temperature and pH for optimal
      growth of fungal mycelia were 25C and pH 7.0, respectively. The fungus
      demonstrated the capacity to degrade cellobiose, starch, and xylan. This is the
      first report on isolation of Mariannaea samuelsii in Korea.

PMID- 22870051
TI  - Fruiting Body Formation of Cordyceps militaris from Multi-Ascospore Isolates and
      Their Single Ascospore Progeny Strains.
AB  - Interest in commercial cultivation and product development of Cordyceps species
      has shown a recent increase. Due to its biochemical and pharmacological effects,
      Cordyceps militaris, commonly known as orange caterpillar fungus, is being
      investigated with great interest. Cultivation of C. militaris has been practiced
      on a large scale in order to fulfill a demand for scientific investigation and
      product development. Isolates of C. militaris can be easily established from both
      spores and tissue. For isolation of spores, ascospores released from mature
      stromata are trapped in sterile medium. Multi-ascospore isolates, as well as
      combinations of single ascospore strains, are used for production of fruiting
      bodies. Progeny ascospore strains can be isolated from artificial fruiting
      bodies, thus, the cycle of fruiting body production can be continued for a long
      period of time. In this study, we examined fruiting body production from multi
      ascospore isolates and their progeny strains for three generations. F(1) progeny
      strains generally produced a larger number of fruiting bodies, compared with
      their mother multi-ascospore isolates; however, F(2) and F(3) progeny strains
      produced fewer fruiting bodies. Optimum preservation conditions could help to
      increase the vitality of the progeny strains. In order to retain the fruiting
      ability of the strains, further testing of various methods of preservation and
      different methods for isolation should be performed.

PMID- 22870052
TI  - Cloning and sequence analysis of the cellobiohydrolase I genes from some
      basidiomycetes.
AB  - Genes encoding the cellobiohydrolase enzyme (CBHI), designated as cbhI, were
      isolated from the basidiomycetes Auricularia fuscosuccinea, Pleurotus giganteus,
      P. eryngii, P. ostreatus, and P. sajor-caju. Initially, the fungal genomic DNA
      was extracted using a modified cetyltrimethyl ammonium bromide (CTAB) protocol
      and used as a DNA template. The cbhI genes were then amplified and cloned using
      the pGEM-T Easy Vector Systems. The sizes of these PCR amplicons were between
      700~800 bp. The DNA sequences obtained were similar showing high identity to the
      cbhI gene family. These cbhI genes were partial consisting of three coding
      regions and two introns. The deduced amino acid sequences exhibited significant
      similarity to those of fungal CBHI enzymes belonging to glycosyl hydrolase family
      7.

PMID- 22870053
TI  - Evaluation of Strains of Metarhizium anisopliae and Beauveria bassiana against
      Spodoptera litura on the Basis of Their Virulence, Germination Rate, Conidia
      Production, Radial Growth and Enzyme Activity.
AB  - Ten strains of the entomopathogenic fungi Metarhizium anisopliae and Beauveria
      bassiana were evaluated to find the most effective strain for optimization
      studies. The first criterion tested for strain selection was the mortality (>
      50%) of Spodoptera litura larvae after inoculation of the fungus for 4 days.
      Results on several bioassays revealed that B. bassiana BNBCRC showed the most
      virulence on mortality S. litura larvae (80% mortality). B. bassiana BNBCRC also
      showed the highest germination rate (72.22%). However, its conidia yield (7.2 *
      10(8) conidia/mL) was lower than those of B. bassiana B 14841 (8.3 * 10(8)
      conidia/mL) and M. anisopliae M6 (8.2 * 10(8) conidia/mL). The highest
      accumulative radial growth was obtained from the strain B14841 (37.10 mm/day)
      while the strain BNBCRC showed moderate radial growth (24.40 mm/day). M.
      anisopliae M6 possessed the highest protease activity (145.00 mU/mL) while M.
      anisopliae M8 possessed the highest chitinase activity (20.00 mU/mL) during
      96~144 hr cultivation. Amongst these criteria, selection based on virulence and
      germination rate lead to the selection of B. bassiana BNBCRC. B. bassiana B14841
      would be selected if based on growth rate while M. anisopliae M6 and M8 possessed
      the highest enzyme activities.

PMID- 22870054
TI  - Inhibitory effects of ethanol extracts from nuruk on oxidative stress,
      melanogenesis, and photo-aging.
AB  - Nuruk contributes to the unique characteristics of Korean alcoholic beverages. In
      this study, the effects of nuruk extracts (NE) on anti-oxidant characters,
      melanogenesis, and anti-photoaging activity were investigated. NEs were obtained
      from the 70% ethanol extracts of six types of nuruk, which have been used in
      brewing of fermented alcohol beverages in Korea. First, various antioxidant
      characteristics were identified in terms of 2,2'-azino-bis(3-ethylbenzthiozoline
      6-sulphonic acid) (ABTS) radical scavenging activity, superoxide dismutase (SOD)
      expression, and inhibition of xanthine oxidase activity. NE#4 exhibited potent
      ABTS radical scavenging activity (IC(50) = 19.51 ug/mL). Compared with NE#4,
      relatively lower levels of activity were observed for NE#3 and NE#6, with IC(50)
      values of 90.99 and 76.88 ug/mL, respectively. According to results of western
      blot analysis for determination of SOD expression in H(2)O(2)-treated HepG2
      cells, NE#5 and NE#6 induced a dramatic increase in the expression ratio of SOD,
      compared to the group treated with H(2)O(2) only. Activity of xanthine oxidase,
      which converts xanthine into uric acid, generating superoxide ions, was inhibited
      by NE#4 and NE#6 in a dose-dependent manner. NE#4 induced significant inhibition
      of mushroom tyrosinase activity. A reduction in cellular melanin contents of 80%
      was observed in B16F1 melanocytes treated with NE#5 and NE#6; these effects were
      similar to those of arbutin at 100 uM. In addition, gelatin zymography and
      reverse transcription-PCR analysis were performed for assessment of anti
      photoaging activity of Nuruk. Treatment with NE#6 resulted in dramatically
      inhibited activities of matrix metalloproteinase (MMP)-2/-9, suppressed
      expression of MMP-1, and increased expression of type-1 procollagen. Results of
      gelatin zymography for NE#4 and NE#5 were similar, to a slightly lesser degree.
      These results suggest the potential of NE#4 and NE#6 as natural ingredients for
      use in functional foods and cosmetics.

PMID- 22870055
TI  - Treatment of Atopic Dermatitis Associated with Malassezia sympodialis by Green
      Tea Extracts Bath Therapy: A Pilot Study.
AB  - Multiple treatment modalities, including topical and systemic corticosteroid and
      phototherapy, have been used in treatment of patients with atopic dermatitis.
      However, long-term corticosteroid therapy may have various adverse effects. The
      purpose of this study was to investigate the therapeutic efficacy and safety of
      bath therapy using green tea extracts for treatment of patients with atopic
      dermatitis. A total of four patients with atopic dermatitis were enrolled in this
      study. A Malassezia multiplex detection kit was used in performance of multiplex
      PCR on clinical isolates, which confirmed Malassezia sympodialis. Subjects
      underwent treatment with bath therapy using green tea extracts three times per wk
      for a period of 4 wk. Assessment using the scoring atopic dermatitis (SCORAD)
      index, the visual analogue scale for pruritus, and transepidermal water loss was
      performed weekly. Laboratory tests were performed before and after treatment. All
      patients showed marked improvement on the mean SCORAD and visual analogue scale,
      and a significant decrease in the mean values of serum eosinophil counts was
      observed after treatment. Bath therapy with green tea extract is an effective,
      safe, and nonsteroidal therapy for treatment of patients with atopic dermatitis
      associated with Malassezia sympodialis.

PMID- 22870056
TI  - Slippery Scar: A New Mushroom Disease in Auricularia polytricha.
AB  - A new disease, the slippery scar, was investigated in cultivated bags of
      Auricularia polytricha. This fungus was isolated from the infected mycelia of
      cultivated bags. Based on morphological observation, rDNA-internal transcribed
      spacer and 18S sequence analysis, this pathogen was identified as the Ascomycete
      Scytalidium lignicola. According to Koch's Postulation, the pathogenicity of S.
      lignicola to the mycelia of A. polytricha was confirmed. The parasitism of this
      fungus on mushroom mycelia in China has not been reported before.

PMID- 22870057
TI  - Mushrooms collected from deogyu mountain, muju, Korea and their antioxidant
      activity.
AB  - Mushrooms collected from Deogyu mountain, Korea, in 2011, were identified as four
      classes, four orders, 13 families, 22 genera, and 33 species. In particular,
      agaricales was most abundant and comprised more than 70%. Their antioxidant
      activities were estimated using three different bioassay methods, the 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging assay, 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and reducing power
      assay. As a result, the methanol extracts of Stereum ostrea, Laetiporus
      sulphureus var. miniatus, and Tyromyces sambuceus exhibited potent antioxidant
      activity in all bioassays tested.

PMID- 22870058
TI  - Comparison of Microbial Diversity of Korean Commercial Makgeolli Showing High
      beta-Glucan Content and High Antihypertensive Activity, Respectively.
AB  - We measured physiological functionalities, including antihypertensive angiotensin
      I-converting enzyme inhibitory activity and immun-stimulating beta-glucan content
      for sixty kinds of Makgeolli that is commercially available from the market. As a
      result, we selected R-12 commercial raw Makgeolli, with a high content of immuno
      stimulating beta-glucan, and R-14 commercial raw Makgeolli, exhibiting high
      antihypertensive activity. Due to the similarities in their overall
      physicochemical properties and raw materials used for fermentation, we compared
      the microbial flora in order to investigate the reason for the differences in
      their functionalities. Nested PCR and denaturing gradient gel electrophoresis for
      yeasts and bacteria were performed for analysis of microbial diversity of two
      different kinds of Makgeolli (i.e., R-12, R-14), which showed immuno-stimulating
      beta-glucan content and exhibited a very high level of antihypertensive activity,
      respectively. Analysis of the 18S rDNA amplicon revealed a major presence of the
      yeast strain Pichia burtonii in every Makgeolli sample. Analysis of the 16S rDNA
      amplicon revealed a predominance of lactic acid bacteria, and the most frequent
      lactic acid bacteria were Lactobacillus ingluviei, L. fermentum, and L.
      harbinensis, and Lactobacillus sp. Among these, L. harbinensis was detected only
      in R-12 and L. ingluviei was found only in R-14. Different functionalities from
      the individual commercially available Makgeolli may be attributed to actions of
      different microbial flora during fermentation.

PMID- 22870059
TI  - Neuraminidase Inhibitors from the Culture Broth of Phellinus linteus.
AB  - During the search for neuraminidase inhibitors from medicinal fungi, we found
      that the culture broth of Phellinus linteus exhibited potent inhibitory activity.
      Solvent partition, Sephadex LH-20 column chromatography, and high-performance
      liquid chromatography (HPLC) were performed for purification of two active
      substances from the culture broth. According to (1)H NMR measurements and
      comparison of HPLC retention times with those of authentic compounds, their
      chemical structures were identified as hispidin and hypholomine B. Compounds
      (hispidin) 1 and 2 (hypholomine B) inhibited neuraminidase, with IC(50) values of
      13.1 and 0.03 uM, respectively.

PMID- 22870060
TI  - Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma.
AB  - The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal
      diseases such as tinea pedis (athlete's foot). In this study, we investigated the
      antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced
      by a mutation breeding using gamma ray irradiation, and compared the antifungal
      activity of H. syriacus Ggoma and its parent type. According to the results, the
      methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal
      activity than its parent type against Trichophyton mentagrophytes. Following
      purification through various column chromatographies, the antifungal substance
      was identified as nonanoic acid on the basis of spectroscopic analysis.

PMID- 22870061
TI  - Non-conformal domain decomposition methods for time-harmonic Maxwell equations.
AB  - We review non-conformal domain decomposition methods (DDMs) and their
      applications in solving electrically large and multi-scale electromagnetic (EM)
      radiation and scattering problems. In particular, a finite-element DDM, together
      with a finite-element tearing and interconnecting (FETI)-like algorithm,
      incorporating Robin transmission conditions and an edge corner penalty term, are
      discussed in detail. We address in full the formulations, and subsequently, their
      applications to problems with significant amounts of repetitions. The non
      conformal DDM approach has also been extended into surface integral equation
      methods. We elucidate a non-conformal integral equation domain decomposition
      method and a generalized combined field integral equation method for modelling EM
      wave scattering from non-penetrable and penetrable targets, respectively.
      Moreover, a plane wave scattering from a composite mockup fighter jet has been
      simulated using the newly developed multi-solver domain decomposition method.

PMID- 22870062
TI  - Optical turbulence and spectral condensate in long fibre lasers.
AB  - We study numerically optical turbulence using the particular example of a
      recently created, ultra-long fibre laser. For normal fibre dispersion, we
      observed an intermediate state with an extremely narrow spectrum (condensate),
      which experiences instability and a sharp transition to a fluctuating regime with
      a wider spectrum. We demonstrate that the number of modes has an impact on the
      condensate's lifetime. The smaller the number of modes, the more resistant is the
      condensate to perturbations. Experimental results show a good agreement with
      numerical simulations.

PMID- 22870064
TI  - When malaria slips a vaccine's net.

PMID- 22870063
TI  - The evolutionary consequences of blood-stage vaccination on the rodent malaria
      Plasmodium chabaudi.
AB  - Malaria vaccine developers are concerned that antigenic escape will erode vaccine
      efficacy. Evolutionary theorists have raised the possibility that some types of
      vaccine could also create conditions favoring the evolution of more virulent
      pathogens. Such evolution would put unvaccinated people at greater risk of severe
      disease. Here we test the impact of vaccination with a single highly purified
      antigen on the malaria parasite Plasmodium chabaudi evolving in laboratory mice.
      The antigen we used, AMA-1, is a component of several candidate malaria vaccines
      currently in various stages of trials in humans. We first found that a more
      virulent clone was less readily controlled by AMA-1-induced immunity than its
      less virulent progenitor. Replicated parasites were then serially passaged
      through control or AMA-1 vaccinated mice and evaluated after 10 and 21 rounds of
      selection. We found no evidence of evolution at the ama-1 locus. Instead,
      virulence evolved; AMA-1-selected parasites induced greater anemia in naive mice
      than both control and ancestral parasites. Our data suggest that recombinant
      blood stage malaria vaccines can drive the evolution of more virulent malaria
      parasites.

PMID- 22870065
TI  - Unmet expectations: miR-34 plays no role in p53-mediated tumor suppression in
      vivo.

PMID- 22870066
TI  - 'Expanding your mind': the process of constructing gender-equitable masculinities
      in young Nicaraguan men participating in reproductive health or gender training
      programs.
AB  - BACKGROUND: Traditional forms of masculinity strongly influence men's and women's
      wellbeing. OBJECTIVE: This study has two aims: (i) to explore notions of various
      forms of masculinities in young Nicaraguan men participating in programs
      addressing sexual health, reproductive health, and/or gender equality and (ii) to
      find out how these young men perceive their involvement in actions aimed at
      reducing violence against women (VAW). DESIGN: A qualitative grounded theory
      study. Data were collected through six focus groups and two in-depth interviews
      with altogether 62 young men. RESULTS: Our analysis showed that the informants
      experienced a process of change, labeled 'Expanding your mind', in which we
      identified four interrelated subcategories: The apprentice, The
      responsible/respectful man, The proactive peer educator, and 'The feminist man'.
      The process showed how an increased awareness of gender inequities facilitated
      the emergence of values (respect and responsibility) and behavior (thoughtful
      action) that contributed to increase the informant's critical thinking and agency
      at individual, social, and political levels. The process was influenced by
      individual and external factors. CONCLUSIONS: Multiple progressive masculinities
      can emerge from programs challenging patriarchy in this Latin American setting.
      The masculinities identified in this study show a range of attitudes and
      behaviors; however, all lean toward more equitable gender relations. The results
      suggest that learning about sexual and reproductive health does not directly
      imply developing more gender-equitable attitudes and behaviors or a greater
      willingness to prevent VAW. It is paramount that interventions to challenge
      machismo in this setting continue and are expanded to reach more young men.

PMID- 22870067
TI  - The influence of movement initiation deficits on the quantification of retention
      in Parkinson's disease.
AB  - In patients with an impaired motor system, like Parkinson's disease (PD),
      deficits in motor learning are expected and results of various studies seem to
      confirm these expectations. However, most studies in this regard are behaviorally
      based and quantify learning by performance changes between at least two points in
      time, e.g., baseline and retention. But, performance in a retention test is also
      dependent on other factors than learning. Especially in patients, the functional
      capacity of the control system might be altered unspecific to a certain task and
      learning episode. The aim of the study is to test whether characteristic temporal
      deficits exist in PD patients that affect retention performance. We tested the
      confounding effects of typical PD motor control deficits, here movement
      initiation deficits, on retention performance in the motor learning process. 12
      PD patients and 16 healthy control participants practiced a virtual throwing task
      over 3 days with 24 h rest between sessions. Retention was tested comparing
      performance before rest with performance after rest. Movement initiation deficits
      were quantified by the timing of throwing release that should be affected by
      impairments in movement initiation. To scrutinize the influence of the initiation
      deficits on retention performance we gave participants a specific initiation
      intervention prior to practice on one of the three practice days. We found that
      only for the PD patients, post-rest performance as well as release timing was
      better with intervention as compared to without intervention. Their performance
      could be enhanced through a tuning of release initiation. Thus, we suggest that
      in PD patients, performance decline after rest that might be easily interpreted
      as learning deficits could rather result from disease-related deficiencies in
      motor control.

PMID- 22870068
TI  - FIAEs in Famous Faces are Mediated by Type of Processing.
AB  - An important question regarding face aftereffects is whether it is based on face
      specific or lower-level mechanisms. One method for addressing this is to explore
      how adaptation in upright or inverted, photographic positive or negative faces
      transfers to test stimuli that are either upright or inverted and normal or
      negated. A series of studies are reported in which this is tested using a typical
      face identity aftereffect paradigm in unfamiliar and famous faces. Results showed
      that aftereffects were strongest when the adaptor matched the test stimuli. In
      addition, aftereffects did not transfer from upright adaptors to inverted test
      images, but did transfer from inverted adaptors to upright test images in famous
      faces. However, in unfamiliar faces, a different pattern was observed. The
      results are interpreted in terms of how identity adaptation interacts with low
      level adaptation and highlight differences in the representation of famous and
      unfamiliar faces.

PMID- 22870069
TI  - Face distortion aftereffects in personally familiar, famous, and unfamiliar
      faces.
AB  - The internal face prototype is thought to be a construction of the average of
      every previously viewed face (Schwaninger et al., 2003). However, the influence
      of the most frequently encountered faces (i.e., personally familiar faces) has
      been generally understated. The current research explored the face distortion
      aftereffect in unfamiliar, famous, and personally familiar (each subject's
      parent) faces. Forty-eight adult participants reported whether faces were
      distorted or not (distorted by shifting the eyes in the vertical axis) of a
      series of images that included unfamiliar, famous, and personally familiar faces.
      The number of faces perceived to be "odd" was measured pre- and post-adaptation
      to the most extreme distortion. Participants were adapted to either an
      unfamiliar, famous, or personally familiar face. The results indicate that
      adaptation transferred from unfamiliar faces to personally familiar faces more so
      than the converse and aftereffects did not transfer from famous faces to
      unfamiliar faces. These results are indicative of representation differences
      between unfamiliar, famous, and personally familiar faces, whereby personally
      familiar faces share representations of both unfamiliar and famous faces.

PMID- 22870071
TI  - Do Not Respond! Doing the Think/No-Think and Go/No-Go Tasks Concurrently Leads to
      Memory Impairment of Unpleasant Items during Later Recall.
AB  - Previous research using neuroimaging methods proposed a link between mechanisms
      controlling motor response inhibition and suppression of unwanted memories. The
      present study investigated this hypothesis behaviorally by combining the think/no
      think paradigm (TNT) with a go/no-go motor inhibition task. Participants first
      learned unpleasant cue-target pairs. Cue words were then presented as go or no-go
      items in the TNT. Participants' task was to respond to the cues and think of the
      target word aloud or to inhibit their response to the cue and the target word
      from coming to mind. Cued recall assessed immediately after the TNT revealed
      reduced recall performance for no-go targets compared to go targets or baseline
      cues not presented in the TNT. The results demonstrate that doing the no-think
      and no-go task concurrently leads to memory suppression of unpleasant items
      during later recall. Results are discussed in line with recent empirical research
      and theoretical positions.

PMID- 22870072
TI  - Embodied space in early blind individuals.

PMID- 22870070
TI  - The effects of evidence bounds on decision-making: theoretical and empirical
      developments.
AB  - Converging findings from behavioral, neurophysiological, and neuroimaging studies
      suggest an integration-to-boundary mechanism governing decision formation and
      choice selection. This mechanism is supported by sequential sampling models of
      choice decisions, which can implement statistically optimal decision strategies
      for selecting between multiple alternative options on the basis of sensory
      evidence. This review focuses on recent developments in understanding the
      evidence boundary, an important component of decision-making raised by
      experimental findings and models. The article starts by reviewing the
      neurobiology of perceptual decisions and several influential sequential sampling
      models, in particular the drift-diffusion model, the Ornstein-Uhlenbeck model and
      the leaky-competing-accumulator model. In the second part, the article examines
      how the boundary may affect a model's dynamics and performance and to what extent
      it may improve a model's fits to experimental data. In the third part, the
      article examines recent findings that support the presence and site of boundaries
      in the brain. The article considers two questions: (1) whether the boundary is a
      spontaneous property of neural integrators, or is controlled by dedicated neural
      circuits; (2) if the boundary is variable, what could be the driving factors
      behind boundary changes? The review brings together studies using different
      experimental methods in seeking answers to these questions, highlights
      psychological and physiological factors that may be associated with the boundary
      and its changes, and further considers the evidence boundary as a generic
      mechanism to guide complex behavior.

PMID- 22870073
TI  - Antimicrobial Peptides can Enhance the Risk of Persistent Infections.

PMID- 22870074
TI  - Regulating the Regulator: Phosphorylation of PKC theta in T Cells.

PMID- 22870075
TI  - The Origin and Function of Anti-Fungal Peptides in C. elegans: Open Questions.

PMID- 22870076
TI  - Fractional flow reserve: the past, present and future.
AB  - Revascularization of coronary artery stenosis should be based on the objective
      evidence of ischemia. It is common practice for physicians to make decisions on
      revascularization in the cardiac catheterization laboratory based on the results
      of angiography, despite the fact that angiographic information does not correlate
      well with the functional significance of a coronary lesion. Fractional flow
      reserve (FFR) is a physiologic parameter which can be measured easily during the
      invasive procedure and can assess the functional significance of coronary
      stenosis. FFR-guided revascularization strategy is reported to be more effective
      than angiography-guided strategy in patients with coronary artery disease.
      Moreover, novel technologies based on FFR have been developed and will soon be
      incorporated into clinical practice.

PMID- 22870077
TI  - Is the measurement of epicardial fat in obese adolescents valuable?

PMID- 22870078
TI  - The independent relationship of systemic inflammation with fragmented QRS
      complexes in patients with acute coronary syndromes.
AB  - BACKGROUND AND OBJECTIVES: QRS complex fragmentations are frequently seen on
      routine electrocardiograms with narrow or wide QRS complex. Fragmented QRS
      complex (fQRS) is associated with increased morbidity and mortality, sudden
      cardiac death and recurrent cardiovascular events. In this study, we aimed to
      interrogate the relationship of systemic inflammation with the presence of fQRS
      in patients with acute coronary syndromes (ACS). SUBJECTS AND METHODS: Two
      hundred and twenty eligible patients with ACS that underwent coronary angiography
      were enrolled consecutively in this study. Patients with significant organic
      valve disease and those with any QRS morphology that had a QRS duration >=120 ms
      as well as patients with permanent pacemakers were excluded from this study.
      RESULTS: Patients with fQRS were of a higher age (p=0.02), had increased C
      reactive protein (CRP) levels (p<0.001), prolonged QRS time (p<0.001), extent of
      coronary artery disease (CAD) (p<0.001), creatine kinase-MB (CK-MB) levels
      (p=0.006) and Q wave on admission electrocardiography (p<0.001) in comparison to
      patients with non-fragmented QRS. When we performed multiple logistic regression
      analysis, fQRS was found to be related to increased CRP levels {odds ratio (OR):
      1.2, 95% confidence interval (CI): 1.045-1.316, p=0.007}, QRS duration (OR: 1.1,
      95% CI: 1.033-1.098, p<0.001), extent of CAD (OR: 1.5, 95% CI: 1.023-2.144,
      p=0.037), Q wave (OR: 2.2, 95% CI: 1.084-4.598, p=0.03) and CK-MB levels (OR:
      1.0, 95% CI: 1.001-1.037, p=0.04) independently. CONCLUSION: In our study, we
      found that fQRS was independently related to increased CRP. Fragmented QRS that
      may result as an end effect of inflammation at cellular level can represent
      increased cardiac risk by different causative mechanisms in patients with ACS.

PMID- 22870079
TI  - A comparison of two brands of clopidogrel in patients with drug-eluting stent
      implantation.
AB  - BACKGROUND AND OBJECTIVES: Although generic clopidogrel is widely used, clinical
      efficacy and safety between generic and original clopidogrel had not been well
      evaluated. The aim of this study was to evaluate the clinical outcomes of 2 oral
      formulations of clopidogrel 75 mg tablets in patients with coronary artery
      disease (CAD) undergoing drug-eluting stent (DES) implantation. SUBJECTS AND
      METHODS: Between July 2006 and February 2009, 428 patients that underwent
      implantation with DES for CAD and completed >1 year of clinical follow-up were
      enrolled in this study. Patients were divided into the following 2 groups based
      on treatment formulation, Platless(r) (test formulation, n=211) or Plavix(r)
      (reference formulation, n=217). The incidence of 1-year major adverse
      cardiovascular and cerebrovascular event (MACCE) and stent thrombosis (ST) were
      retrospectively reviewed. RESULTS: The baseline demographic and procedural
      characteristics were not significantly different between two treatment groups.
      The incidence of 1-year MACCEs was 8.5% {19/211, 2 deaths, 4 myocardial
      infarctions (MIs), 2 strokes, and 11 target vessel revascularizations (TVRs)} in
      Platless(r) group vs. 7.4% (16/217, 4 deaths, 1 MI, 2 strokes, and 9 TVRs) in
      Plavix(r) group (p=0.66). The incidence of 1-year ST was 0.5% (1 definite and
      subacute ST) in Platless(r) group vs. 0% in Plavix(r) group (p=0.49). CONCLUSION:
      In this study, the 2 tablet preparations of clopidogrel showed similar rates of
      MACCEs, but additional prospective randomized studies with pharmacodynamics and
      platelet reactivity are needed to conclude whether generic clopidgrel may replace
      original clopidogrel.

PMID- 22870080
TI  - Serial plasma levels of angiogenic factors in patients with ST-segment elevation
      myocardial infarction undergoing primary percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVES: Patients with acute myocardial infarction show varying
      degrees of collateral development. However, the relationships between angiogenic
      factors and degree of collaterals are not well known. SUBJECTS AND METHODS: Fifty
      nine patients (mean age, 59+/-10 years) with ST-segment elevation myocardial
      infarction (STEMI) underwent primary percutaneous coronary intervention (PCI).
      Patients were divided into one of 2 groups: group I (Rentrop collateral grade
      0/1, n=34) or group II (grade 2/3, n=25). Plasma levels of vascular endothelial
      growth factor (VEGF), soluble VEGF receptor (sFlt-1), angiopoietin (Ang)-2, and
      soluble Tie-2 at baseline, 24 and 48 hours after PCI were measured. RESULTS:
      There were fewer diabetic patients and higher incidence of previous angina and
      multi-vessel disease in group II. Group II had a lower left ventricular ejection
      fraction and a trend toward longer pain-to-balloon time. Plasma levels of Ang-2,
      sFlt-1 were elevated prior to primary PCI and decreased after PCI, whereas plasma
      level of VEGF was relatively low initially, however rose after PCI. sTie-2 levels
      showed no significant interval change in group I, but decreased over time in
      group II. VEGF, sFlt-1, and Tie-2 levels did not differ between the groups at
      each time point. However, plasma levels of Ang-2 were higher in group I than in
      group II at baseline and at 48 hours. CONCLUSION: Presence of collaterals in
      STEMI patients undergoing primary PCI was associated with lesser rise in Ang-2
      plasma level. VEGF showed a delayed response to acute ischemia compared to Ang-2.
      Clinical implications of our findings need to be investigated in further studies.

PMID- 22870081
TI  - Correlation between epicardial fat thickness by echocardiography and other
      parameters in obese adolescents.
AB  - BACKGROUND AND OBJECTIVES: Obesity has reached epidemic proportions globally and
      affects people of all ages. Recent studies have shown that visceral adipose
      tissue measured by magnetic resonance imaging and/or computed tomography
      correlates positively with epicardial adipose tissue. Epicardial fat, which is
      correlated to several metabolic parameters, can be assessed by echocardiography.
      The aim of this study was to evaluate epicardial fat thickness and other
      metabolic parameters in obese adolescents and investigate the correlation between
      epicardial fat thickness and other metabolic parameters in obese adolescents.
      SUBJECTS AND METHODS: We selected 99 subjects, between ages 15-17 years of age,
      to be enrolled in this study. Sixty five obese adolescents with a body mass index
      (BMI) >95 percentile and 34 control subjects were included in this study.
      Echocardiographic measurements including epicardial fat thickness as well as
      anthropometric and blood pressure (BP) measurements were performed. The following
      parameters were estimated: blood glucose, total cholesterol, triglyceride, high
      density lipoprotein-cholesterol, low density lipoprotein-cholesterol, aspartate
      aminotransferase, alanine aminotransferase, free fatty acid, interleukin-6, tumor
      necrosis factor-alpha, leptin, adiponectin and high sensitive C reactive protein.
      RESULTS: The obese group showed a statistically significant correlation with
      echocardiographic epicardial fat thickness and, BMI, waist circumference, obesity
      index, fat percentage, systolic BP, insulin level, leptin and adiponectin.
      Multivariate linear regression analysis showed epicardial fat thickness as the
      most significant independent parameter to correlate with obese adolescents.
      CONCLUSION: These data suggest that epicardial fat thickness measured by
      echocardiography is a practical and accurate parameter for predicting visceral
      obesity.

PMID- 22870082
TI  - Probing regulatory proteins for vascular contraction by deoxyribonucleic Acid
      microarray.
AB  - BACKGROUND AND OBJECTIVES: The heat-shock response modulates contractility of
      vascular smooth muscles. With complementary deoxyribonucleic acid microarray, we
      tried to identify the novel genes that are involved in the regulation of vascular
      contraction after heat shock. MATERIALS AND METHODS: Human radial artery strips
      were mounted in organ baths, exposed at 42C for 45 minutes, and returned to
      equilibrate at 37C. This study examined gene expression profile associated with
      heat-shock response in radial arteries of patients with hyperlipidemia by using a
      microarray that contained 5763 human cDNA. The results of microarray
      hybridization experiments from the radial arteries of 4 different subjects were
      analyzed and classified by the cluster program. RESULTS: Among these
      differentially-expressed genes, Hsp70, Hsp10, alphaB-crystallin, and Hsp60 were
      significantly increased by the heat shock response. Of non-HSP genes, 15 genes
      increased, while 22 genes decreased. Among these 37 genes, alphaB-crystallin
      (CRYAB) (up 1.92-fold), myosin, light polypeptide kinase transcript variant 8, 6
      (up 1.70-fold, up 1.68-fold), catenin (cadherin-associated protein, alpha-like 1)
      (down-0.57 fold) and tropomyosin 3 (down 0.68-fold) were thought to be related
      with the contraction. Real-time quantitative polymerase chain reaction showed
      that Hsp70, Hsp10 and alphaB-crystallin were significantly increased. CONCLUSION:
      Gene expression profile by heat shock provides information about genes implicated
      in augmentation of vascular contraction after heat shock.

PMID- 22870083
TI  - Acute coronary stent thrombosis in cancer patients: a case series report.
AB  - There have been a growing numbers of patients diagnosed with malignancy and
      coronary artery disease simultaneously or serially. In the era of percutaneous
      coronary intervention (PCI), stent thrombosis has been a rare but challenging
      problem. Recently, we experienced two unique cases of acute stent thrombosis in
      patients with malignancy. The first case showed acute and subacute stent
      thrombosis after PCI. The second case revealed simultaneous thromboses in stent
      and non-treated native coronary artery. We believe that we need rigorous
      precautions in the treatment of patients with coronary artery disease and
      malignancy, especially with regards to deciding how and whether to revascularize,
      as well as which anti-platelet agents to select.

PMID- 22870084
TI  - Successful retrieval of intravascular stent remnants with a combination of
      rotational atherectomy and a gooseneck snare.
AB  - Stent migration from the delivery balloon catheter is a rare but serious
      complication during percutaneous coronary intervention, particularly when a part
      of the stent stretches into the aorta. We report an unusual case of stent
      migration treated with a combination of a gooseneck snare and rotablation. A part
      of the stent was overstretched and unrolled into the aorta and the rest of the
      stent remained implanted in the coronary artery. The stent was captured with a
      gooseneck snare but could not be retrieved because it was connected to a stent
      remnant implanted in the coronary artery. The stent strut was cut with
      rotablation, and the stent was successfully removed through the femoral sheath.

PMID- 22870085
TI  - Successful percutaneous coronary intervention in an anomalous origin of the right
      coronary artery from the ascending aorta above the left sinus of the valsalva.
AB  - The anomalous origin of the right coronary artery (RCA) is a rare condition. Most
      RCA anomalies are usually found incidentally, but these findings have clinical
      significance because many patients, particularly young ones, present with sudden
      death, myocardial ischemia and syncope without other symptoms. We describe a case
      of a 39-year-old male patient that presented with effort chest pain and was
      diagnosed with anomalous RCA that originated from the ascending aorta with prior
      history of repairing ruptured sinus valsalva and ventricular septal defect. The
      anomalous origin of RCA was identified by multidetector computed tomography
      (MDCT). Successful percutaneous coronary intervention was performed guided by
      MDCT coronary images and intravascular ultrasound.

PMID- 22870086
TI  - Staphylococcus aureus pericardial abscess presenting as severe sepsis and septic
      shock after acupuncture therapy.
AB  - Pericardial abscess is an extremely rare complication of Staphylococcus aureus
      bacteremia. We report a case of a 72-year-old woman with multiple acupuncture
      scars on both knees who presented with shortness of breath and general weakness.
      Transthoracic echocardiography and pericardiocentesis confirmed the presence of
      pericardial fluid collection. Staphylococcus aureus grew in both pericardial
      fluid and blood. Although an aggressive medical treatment including intravenous
      antibiotics and percutaneous drainage, the patient died 2 days after admission.

PMID- 22870087
TI  - Iatrogenic bidirectional dissection of the right coronary artery and the
      ascending aorta: the worst nightmare for an interventional cardiologist.
AB  - Although rare, iatrogenic aortocoronary dissection is one of the complications
      most dreaded by the interventional cardiologist. If not managed promptly, it can
      have redoubted and serious consequences. Herein, we present the case of a 70 year
      old woman who was treated by stenting of the second segment of the right coronary
      artery (RCA) for recurrent angina but, unfortunately, the procedure was
      complicated by anterograde dissection of the RCA with a simultaneous retrograde
      propagation to the proximal part of the ascending aorta. Successful stenting of
      the entry point was able to recuperate the RCA and to limit the retrograde
      propagation to the ascending aorta, but there was an extension of the dissection
      to the aortic valve leaflets resulting in a massive aortic insufficiency.
      Therefore, surgical aortic valve replacement with prosthetic tube graft was
      performed [corrected].

PMID- 22870089
TI  - Retraction: Aortic dissection and rupture in a child.

PMID- 22870088
TI  - Ortner syndrome due to concomitant mitral stenosis and bronchiectasis.
AB  - Ortner syndrome or cardiovocal syndrome is a rare condition characterized by
      hoarseness of voice associated with cardiovascular pathology. Compression of the
      left recurrent laryngeal nerve by the pulmonary artery or left atrium is usually
      responsible. Recurrent aspiration pneumonia may cause significant morbidity and
      mortality. Early recognition and treatment along with removal of the underlying
      cause, if possible, may change an otherwise poor prognosis of the condition. The
      case presented here describes a 35-year old female with hoarseness of voice in
      association with mitral stenosis and bronchiectasis. Presence of dual pathology
      contributed to the overall pathophysiology of the disease, and made its
      management difficult.

PMID- 22870090
TI  - MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical
      applications (Review).
AB  - MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 base pairs that
      regulate the expression of genes by targeting messenger RNA with complementarity
      with the miRNA base sequence. Regulation of gene expression by miRNAs is crucial
      in cellular development and differentiation, and recent studies suggest a
      relationship between human diseases and the breakdown of gene silencing
      mechanisms induced by miRNA abnormalities. In particular, abnormal miRNA
      expression has been detected in various types of cancer and the target genes have
      been identified. These results indicate that miRNAs act in a manner equivalent to
      oncogenes or tumor suppressors. miRNAs may also serve as diagnostic biomarkers
      and therapeutic targets. In this review, we introduce the latest findings on
      miRNAs in human endometrial cancer, a common malignancy, and discuss the
      potential of miRNAs as biomarkers and targets for molecular therapy.

PMID- 22870091
TI  - Spontaneous regression of malignant tumors: Importance of the immune system and
      other factors (Review).
AB  - It has been established that malignant tumors as well as metastases, of almost
      all histological types, can regress spontaneously although certain histological
      types regress more frequently than others. Various causes thereof include
      apoptosis, the immune system and particular conditions of the tumor
      microenvironment. The action of the genome in the regression of tumors is not
      clear, but some data, apart from those of apoptosis, support its involvement. The
      hypothesis that the immune system exhibits variations in efficacy, even to a
      marked extent, in determining partial or total regression of tumors appears to be
      plausible. Such variable efficacy may be supported by blockage of growth and the
      proliferation of cancer cells at the level of the tumor microenvironment, the
      intervention of various factors such as inhibitors of metalloproteinases and
      angiogenesis, and the absence or scarcity of particular proteins. The consequence
      of such a blockage would be a relative increase in the number of natural killer
      cells and other elements involved in the immune system in relation to the number
      of circulating cancer cells in the blood. A relative increase in the number of
      elements of the immune system is more effective than an absolute increase, since
      an absolute increase is able to stimulate, as frequently occurs for feedback in
      biological equilibria, inhibitor receptors that reduce the efficacy of the same
      elements (mainly natural killer and CD8(+) T cells). Such an increase in the
      efficacy of the immune system can lead, at least in certain cases, to the so
      called spontaneous regression of malignant tumors. Clinical practice has
      demonstrated that metastases are less frequent in patients with renal carcinoma
      undergoing hemodialysis compared with patients with renal carcinoma not on
      hemodialysis. This finding can be interpreted, in correlation with the blockage
      of cancer cells in tissues, as a consequence of a partial blockage of metastatic
      cancer cells at the level of the dialytic membrane, with a subsequent increase in
      the relative efficacy of the immune system.

PMID- 22870092
TI  - Absence of the JAZF1/SUZ12 chimeric transcript in the immortalized non-neoplastic
      endometrial stromal cell line T HESCs.
AB  - Endometrial stromal sarcomas are rare malignancies, accounting for less than 10%
      of uterine sarcomas. The most characteristic chromosomal aberration of this tumor
      type is the translocation t(7;17)(p15-p21;q12-q21) leading to the fusion of two
      zinc finger genes, JAZF1 and SUZ12. Recently, the presence of the neoplastic
      JAZF1/SUZ12 fusion transcript was reported in normal cells of human endometrium.
      One of the positive samples for the JAZF1/SUZ12 transcript was the immortalized T
      HESCs cell line. This cell line was derived from the stromal cells obtained from
      an adult female with myomas and immortalized by transfection of a human
      telomerase gene. Since T HESCs has a normal karyotype and no fusion of the two
      genes occurs at the genomic level, the JAZF1/SUZ12 transcript was proposed to be
      generated by regulated trans-splicing between precursor RNAs for JAZF1 and SUZ12.
      However, no confirmatory reports currently exist. To determine whether the
      results could be reproduced, the T HESCs cell line was subjected to three
      different RT-PCR amplifications for the JAZF1/SUZ12 fusion transcript. RT-PCR
      assays did not amplify JUZF1/SUZ12 cDNA fragments in the T HESCs cell line,
      whereas the same assays easily generated JUZF1/SUZ12-amplified transcripts in an
      endometrial stromal cell sarcoma carrying the t(7;17) chromosomal aberration.
      Thus, the presence, if any, of a JUZF1/SUZ12 chimeric transcript in the
      immortalized normal T HESCs is not a constant, reproducible result.

PMID- 22870093
TI  - Insertion of the 3' ABL region into the long arm of chromosome 1 in a
      Philadelphia chromosome-negative chronic myeloid leukemia case.
AB  - Chronic myeloid leukemia (CML) is a pluripotent hematopoietic stem cell disorder
      almost always characterized by the presence of the Philadelphia chromosome (Ph),
      usually due to t(9;22)(q34;q11). The presence of Ph results in the formation of
      the BCR/ABL fusion gene, which is a constitutively activated tyrosine kinase.
      Approximately 1% of CML patients appear to have a Ph-negative karyotype but carry
      a cryptic BCR/ABL fusion that can be located by fluorescence in situ
      hybridization (FISH) at chromosome 22q11, 9q34 or a third chromosome. This study
      investigated a rare Ph-negative CML case with insertion of the 3' ABL region into
      the long arm of derivative chromosome 1 but lacking the 5' BCR region on der(22).

PMID- 22870094
TI  - Inhibition of pleural metastasis of collecting duct carcinoma of the kidney by
      modified cytokine-induced killer cells: A case report and review of the
      literature.
AB  - Collecting duct carcinoma (CDC) or Bellini duct carcinoma of the kidney is a
      rare, but highly aggressive renal epithelial malignancy, with an extremely poor
      prognosis. Modified cytokine-induced killer (mCIK) cells were injected into the
      pleural cavity to treat pleural metastasis of CDC. The patient, a 33-year-old
      male, was admitted to hospital for further treatment for severe pleural
      metastasis of CDC. We cured the pleural metastasis through intrapleural infusion
      with mCIK cells. After receiving this innovative treatment, the patient exhibited
      a positive response: the cough, dyspnea, chest distress and thoracalgia were
      evidently relieved, while the pleural fluid became clear after exhibiting
      haematodes and its level decreased significantly. The patient achieved partial
      success. This novel immunotherapy method is a promising treatment for patients
      with refractory pleural metastasis.

PMID- 22870095
TI  - Expression of adhesion molecules and transforming growth factor-beta in
      pleomorphic carcinomas of the lung.
AB  - Pleomorphic carcinoma (PC) of the lung consists of an epithelial component
      showing the histology of poorly differentiated non-small cell carcinoma of the
      lung and a sarcomatous component, that is more aggressive compared to non-small
      cell carcinoma of the lung. To determine the differences between an epithelial
      component of PC and poorly differentiated non-small cell carcinoma, the
      expression of adhesion molecules (E-cadherin, beta-catenin and N-cadherin) and
      transforming growth factor-beta (TGF-beta) was compared immunohistochemically
      among 14 poorly differentiated adenocarcinomas of the lung (PDAs) and 14 PCs of
      the lung, with an epithelial component, showing the histology of PDA. Expression
      levels of E-cadherin and beta-catenin were significantly lower in epithelial or
      sarcomatous components of PCs than in PDAs while that of TGF-beta was
      significantly higher in epithelial components of PCs than in PDAs. No significant
      difference was found in incidences of the expression of these molecules between
      epithelial and sarcomatous components of PCs. No significant difference was noted
      in the expression level of N-cadherin among PDAs and epithelial and sarcomatous
      components of PCs. The present results showed that E-cadherin and beta-catenin
      expression is reduced and TGF-beta expression is increased in epithelial
      components of PCs with the same histology as PDA when compared to PDAs,
      suggesting that an epithelial component of PC is distinct from non-small cell
      carcinoma with the same histology.

PMID- 22870096
TI  - Surgical management of metastatic adrenal tumors: Decision-making factors in
      imaging.
AB  - The present study aimed to clarify decision-making factors based on imaging for
      laparoscopic adrenalectomy (LA) or open adrenalectomy (OA) for adrenal metastasis
      (AM) based on our previous experience. From November 2003 to November 2006, 11
      adrenalectomies were performed for AM for malignancies such as lung cancer, renal
      cell carcinoma (RCC) and breast cancer at Tokai University Hospital. A diagnosis
      of AM for these malignancies was suspected whenever a newly diagnosed adrenal
      mass was located, characterized by a basal computed tomography (CT) density
      superior to 10 Hounsfield units, strong or heterogeneous vascular enhancement
      following contrast injection and/or increasing size in sequential imaging
      studies. There was no evidence of extra-AM. The approach to surgical management
      using LA or OA was determined on the basis of CT and/or magnetic resonance
      imaging. The patients were reviewed every 2 or 3 months by physical examination
      and systemic CT. We analyzed the decision-making factors based on imaging for
      surgical management with LA or OA from the results of oncological outcome,
      imaging, intraoperative and pathohistological findings. In this study, 9 patients
      underwent 11 adrenalectomies (9 laparoscopic and 2 open procedures). Non-small
      cell lung cancer was the most common primary malignancy (5 adrenalectomies of 4
      patients), followed by RCC (4 adrenalectomies of 4 patients) and breast cancer (2
      adrenalectomies of 1 patient). The median tumor size for the LA group was 3.1+/
      0.7 cm (range 2.1-4.3) and for the OA group, 6.1+/-0.8 cm (5.5 and 6.7 cm)
      (p=0.001). The operative time for the LA group was 127+/-42 min (range 90-215)
      and for the OA group, 224+/-47 min (190 and 257 min) (p=0.018). Blood loss for
      the LA group was 49+/-63 g (range 3-207) and for the OA group, 340+/-10 g (333
      and 347 g) (p<0.001). No complications were noted and no conversion of LA to OA
      occurred. All 9 adrenal tumors selected for LA were removed safely without strong
      adhesion to the surrounding tissue. Two adrenal tumors removed by OA had a strong
      adhesion to the surrounding tissue. All 9 patients had complete resection,
      without capsular disruption and a negative margin in the pathological findings.
      No port-site and local recurrences occurred. No patients presented with local
      relapse or port-site metastasis. Disease-free survival rate for the LA group was
      57% and for the OA group, 50% (p=0.661). LA is a less invasive treatment than OA
      for AM. However, for complete resection, OA should be selected for cases where
      resection by LA is difficult. Therefore, in the decision making towards the
      appropriate surgical management with LA or OA, it is important to closely assess
      pre-operative imaging. Imaging features supporting OA include no detection of
      fatty tissue between the tumor and proximal organs, tumors with an irregular
      contour, large tumors and tumors with a cystic component.

PMID- 22870097
TI  - Effect of leucovorin on the antitumor efficacy of the 5-FU prodrug, tegafur
      uracil, in human colorectal cancer xenografts with various expression levels of
      thymidylate synthase.
AB  - The combination of oral tegafur-uracil (UFT) with leucovorin (LV) is used to
      treat patients with stage II to III colon cancer based on the results of
      postoperative randomized studies in which UFT/LV treatment showed an equivalent
      efficacy to intravenous 5-FU plus LV therapy. However, whether the addition of LV
      to UFT can elevate the antitumor activity of UFT in colorectal tumors with high
      expression levels of thymidylate synthase (TS), which affects 5-FU efficacy,
      remains to be clarified. This study investigated the effect of LV on the
      antitumor activity of UFT and/or 5-FU prodrugs in low folate diet-fed nude mice
      using human colorectal cancer xenografts with various expression levels of TS.
      The addition of LV to UFT resulted in a 55-79% inhibition of tumor growth among
      11 types of colorectal tumor xenograft, whereas UFT alone showed 23-67% antitumor
      activity. Although there was an inverse relationship between the antitumor effect
      of UFT alone and UFT plus LV and tumoral TS activity, UFT plus LV appeared to
      have a more potent antitumor effect than UFT alone on colorectal tumors such as
      Co-3 and KM12C/5-FU with high expression levels of TS. This finding was confirmed
      by the significant positive correlation between the relative inhibition ratio of
      UFT/LV to UFT alone and TS levels in tumors. To investigate the reason for the
      higher efficacy of UFT/LV on colorectal cancer xenografts with high TS activity,
      intratumoral levels of reduced folates and a ternary complex of TS after oral UFT
      with or without LV were measured using Co-3 xenografts. Elevated levels of
      reduced folates and an increased ternary complex of TS in LV-treated tumors were
      noted. Our results indicate that a combined therapy of UFT with LV may contribute
      to the treatment of colorectal cancer patients with low and high expression
      levels of tumoral TS by increased formation of the ternary complex of TS leading
      to potentiated antitumor efficacy of UFT.

PMID- 22870098
TI  - A retrospective study on TS mRNA expression and prediction of the effects of
      adjuvant oral 5-fluorouracil in breast cancer.
AB  - Nucleic acid-metabolizing enzymes, such as thymidylate synthase (TS),
      dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate
      phosphoribosyl transferase (OPRT), have attracted attention as candidates for
      response determinants of 5-fluorouracil (5-FU). Whether the expression levels of
      these enzymes can be adopted as valuable parameters for 5-FU sensitivity in
      breast cancer has yet to be elucidated. In the present study, intratumoral mRNA
      expression of TS, DPD, TP and OPRT were determined in formalin-fixed paraffin
      embedded surgical specimens collected from 217 breast cancer patients, using the
      Danenberg Tumor Profile method, which combines microdissection and real-time
      polymerase chain reaction. The significance of these enzymes as prognostic and 5
      FU efficacy-predicting factors was evaluated. Our data showed that a low DPD
      expression is related to a high nuclear grade and other factors including hormone
      receptor-negativity. Low expression levels of TP were found in hormone receptor
      negative tumors. TS and OPRT expression were not related to various
      clinicopathological factors, but patients with a high TS mRNA expression showed a
      significantly poorer prognosis in cases where 5-FU was not administered. The
      efficacy of 5-FU was more significant when administered for more than 6 months in
      the group with a high TS mRNA expression. These data suggest that TS mRNA
      expression in breast cancer tissue is an ideal predictor of outcomes for patients
      with no administration of 5-FU, and of the efficacy of 5-FU.

PMID- 22870099
TI  - Type IV collagen levels are elevated in the serum of patients with peritoneal
      dissemination of gastric cancer.
AB  - Type III procollagen (amino-terminal propeptide of procollagen type III) and type
      IV collagen are considered to be reliable serum markers for monitoring the
      progression of liver fibrosis. The peritoneal dissemination of gastric cancer is
      also characterised by abundant collagen deposition in the peritoneum. The present
      study was performed to investigate the potential of serum type III procollagen
      and IV collagen as biomarkers for peritoneal dissemination in gastric cancer. The
      study population consisted of 117 patients with gastric cancer: 32 patients had
      peritoneal dissemination which was pathologically diagnosed by laparotomy or
      laparoscopic examination, while 85 patients (45/40, early/advanced gastric
      cancer) had no peritoneal dissemination. We measured the serum levels of type III
      procollagen and type IV collagen in comparison to the commonly accepted tumor
      markers carcinoembryonic (CEA), carbohydrate antigen (CA)19-9 and CA125. The
      median type III procollagen levels showed no significant differences between the
      two groups, whereas the median type IV collagen levels were significantly (201
      ng/ml) higher in patients with than in those without peritoneal dissemination
      (early/advanced gastric cancer, 124/136 ng/ml) (P<0.05). In receiver operating
      characteristic (ROC) curve analysis, type IV collagen had the largest area under
      the curve (0.83), followed by CA125 (0.72), CA19-9 (0.64), CEA (0.59) and type
      III procollagen (0.48). Type IV collagen was an independent marker (P<0.0001,
      odds ratio 15.7) for predicting peritoneal dissemination along with CA125
      (P=0.0086, odds ratio 9.4) based on multivariate logistic regression. In
      conclusion, serum type IV collagen levels may be significant in the early
      detection and management of patients with peritoneal dissemination of gastric
      cancer.

PMID- 22870100
TI  - Gallbladder carcinoma with a large monolocular cystic cancerous component.
AB  - The monolocular cystic formation associated with gallbladder carcinoma is an
      extremely rare condition. A 79-year-old female suffering from upper abdominal
      pain and distention was admitted to our hospital. Ultrasonography and computed
      tomography revealed a monolocular cyst with an irregular wall thickness of 15 cm
      in diameter concomitant with a solid mass of 8 cm in diameter around the
      gallbladder bed. During celiotomy, the tumor was found to have a large pale gray
      cystic component at the fundus of the gallbladder, and disseminated nodules were
      observed in the peritoneum. We diagnosed the patient with gallbladder carcinoma
      and performed a simple cholecystectomy that included the tumor without systematic
      lymphadenectomy. On the cut face of the gallbladder, the lumen was occupied by a
      solid neoplasm. The cyst included a large amount of serous fluid and protruded
      continuously from the body of the gallbladder, but it did not communicate with
      the gallbladder lumen. Although the mechanism responsible for the development of
      cyst-forming papillary carcinoma of the gallbladder remains unknown, the present
      case is crucial for understanding the mechanism of cystogenesis in gallbladder
      carcinoma.

PMID- 22870101
TI  - Changes in 2'-deoxycytidine levels in various tissues of tumor-bearing mice.
AB  - The nucleoside 2'-deoxycytidine (dCyd) increases in the plasma of cancer patients
      with poor prognoses. 5-fluorouracil (5FU) is one of the anti-cancer agents used
      in chemotherapy for patients whose plasma dCyd is elevated. We examined the free
      dCyd level in various tissues of mice, with and without tumors, and in mice with
      and without the administration of 5FU or of dCyd, and investigated the effects of
      dCyd in tumor-bearing animals. SP2/0-Ag14 mouse myeloma cells were transplanted
      subcutaneously into mice and 5FU or dCyd was administered intraperitoneally. Free
      dCyd was measured in blood and tissues by HPLC at two time points, once when
      mouse body weight was maximally decreased (1 day after the last administration of
      5FU, day 16) and again when it returned to control level at 1 week after the last
      5FU treatment (day 22). Results showed that in tumor-bearing mice, the level of
      dCyd (per g wet weight) increased in the spleen. The change in liver weight
      caused by the administration of 5FU correlated with the level of dCyd in the
      liver. Notably, the relative tumor volume and tumor weight was decreased in dCyd
      treated animals in comparison with controls. In conclusion, the levels of dCyd
      were markedly altered in the tissues of the reticuloendothelial and lymphatic
      systems, such as liver and spleen, and dCyd apparently had the ability to inhibit
      tumor growth in the body.

PMID- 22870102
TI  - Surgical strategy of brain tumors adjacent to the optic radiation using diffusion
      tensor imaging-based tractography.
AB  - The present study evaluated the efficacy of diffusion tensor imaging (DTI)-based
      tractography in the surgery of brain tumors adjacent to the optic radiation. Of
      the 14 surgical cases included, 11 had metastatic brain tumors and 3 cerebral
      gliomas. Additionally, 4 of the 14 patients had pre-operative visual field
      defects, while the remaining 10 patients experienced no visual impairment. The
      optic radiations on the lesion side were evident in all 14 patients. On the basis
      of these tractographic findings, we employed optimal surgical approaches in each
      patient to avoid injury to the eloquent neural structures, including optic
      radiation, during surgery. Successful surgical resection was performed in all 14
      patients. Of the 14 patients, 2 with visual field defects during the pre
      operative period showed improvement in their visual field, and the remaining 12
      patients experienced no visual deterioration. DTI-based tractography thus is a
      feasible modality for the surgical planning of brain lesions adjacent to the
      optic radiation.

PMID- 22870103
TI  - HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a
      Smad-independent manner.
AB  - Epithelial to mesenchymal transition (EMT) is induced by transforming growth
      factor-beta1 (TGF-beta1) and is a crucial event for cancer cells to acquire
      invasive and metastatic phenotypes. However, the signals that induce EMT in
      cancer cells have yet to be adequately defined. In this study, a proteomic
      investigation was performed to understand the signaling pathway of the EMT of
      lung cancer using two-dimensional difference gel electrophoresis (2D-DIGE) and
      mass spectrometry. The protein expression profiles of A549 were compared to those
      of A549 cells treated with TGF-beta1. Of more than 2,000 protein spots shown by
      2D-DIGE, 53 were found to be up- or down-regulated upon induction with TGF-beta1.
      In the 53 protein spots, the protein level of heat shock protein (HSP) 27 was
      found to increase significantly. HSP27 protein was higher in two different lung
      cancer cell lines, demonstrating the EMT phenomenon with TGF-beta1. Notably, the
      silencing of HSP27 enhanced spindle integration, resulting in an additive effect
      with TGF-beta1-induced EMT. Furthermore, the TGF-beta1-induced HSP27 increase was
      not affected by the suppression of Smad2 and Smad3 in A549 cells. These results
      suggest that HSP27 was involved in TGF-beta1-induced EMT in a Smad-independent
      manner in lung cancer cells and may provide an effective clinical strategy in
      lung cancer patients whose tumors are dependent on TGF-beta1-induced EMT.

PMID- 22870104
TI  - Heterozygous mutation (G/G->G/A) at nt 2607 of the EGFR gene is closely
      associated with increases in EGFR copy number and mRNA half life, but impaired
      EGFR protein synthesis in squamous cell carcinomas of the head and neck -
      implication for gefitinib efficacy.
AB  - Gefitinib (ZD1839, Iressa((r))) is an orally active agent that inhibits the
      tyrosine kinase activity of epidermal growth factor receptor (EGFR). Gefitinib
      has shown a high efficacy in patients with non-small cell lung carcinoma and
      specific mutations in the ATP-binding pocket of EGFR. These mutations, however,
      are extremely rare in squamous cell carcinomas of the head and neck (SCCHN). We
      previously showed that SCCHN cell lines with a heterozygous mutation (G/G->G/A)
      at nucleotide 2607 of EGFR are more sensitive to gefitinib than wild-type cell
      lines (79.5% higher IC(50)). To determine the relationship between the G/G and
      G/A genotypes, we assessed the EGFR gene copy number and the EGFR mRNA half-life
      in 16 different SCCHN cell lines. Fluorescence in situ hybridization showed that
      the EGFR copy number was significantly higher in the nine 2607G/A cell lines than
      in the seven 2607G/G cell lines (3.59+/-2.14 vs. 1.58+/-0.32 copies, a 2.27-fold
      difference). Similarly, the half life of EGFR mRNA was 2.24-fold higher in cell
      lines with the 2607G/A genotype than in those with wild-type. By contrast, the
      EGFR protein levels were inversely correlated with mRNA abundance. These findings
      suggest that sensitivity to gefitinib of cells with the heterozygous mutation
      (2607G/G->G/A) was closely associated with gene amplification, the prolongation
      of mRNA half-life and a decrease in EGFR protein.

PMID- 22870105
TI  - Usefulness of desensitization protocol for a carboplatin hypersensitivity
      reaction during docetaxel-carboplatin therapy for recurrent ovarian cancer: Case
      report.
AB  - We report a case of recurrent ovarian cancer in which desensitization for a
      carboplatin hypersensitivity reaction proved useful. The patient was a 65-year
      old woman who presented with a recurrence of stage IIIc ovarian cancer. The
      initial chemotherapy consisted of 6 courses of paclitaxel and carboplatin.
      Recurrence in the pelvis, splenic hilum and para-aortic lymph nodes was detected
      19 months after the final day of treatment. The patient was treated with
      docetaxel-carboplatin therapy for the recurrence, but a Grade 3 hypersensitivity
      reaction to carboplatin was observed during the second course. Carboplatin
      desensitization was commenced with the third course and 6 courses were completed
      with no evidence of hypersensitivity reaction. The antitumor effect showed a
      complete response and the patient has had a disease-free survival thus far.
      Desensitization for patients diagnosed with a carboplatin hypersensitivity
      reaction appeared to be a key method of treatment for prolonging the survival
      time of patients with recurrent ovarian cancer.

PMID- 22870106
TI  - Development of a novel enzyme-targeting radiosensitizer (KORTUC) containing
      hydrogen peroxide for intratumoral injection for patients with low linear energy
      transfer-radioresistant neoplasms.
AB  - The therapeutic effect of radiotherapy using linear accelerators for relatively
      large tumors of more than several centimeters in diameter is reduced to one third
      due to a large number of hypoxic tumor cells and a significant amount of anti
      oxidative enzymes including peroxidase/catalase. The most effective method by
      which to inject hydrogen peroxide into tumor tissue was examined. This proved
      difficult as 3% w/v hydrogen peroxide solution (Oxydol) is an antiseptic agent
      for skin lesions. Thus, injection into an affected lesion may result in hydrogen
      peroxide soaking into a body cavity, possibly causing an intra-arterial oxygen
      embolism. This study aimed to identify the most effective combination of drugs
      containing hydrogen peroxide in order to relieve local pain at the injection site
      and preserve high intratumoral oxygen concentration. Hyaluronate-hydrogen
      peroxide was identified as the most effective combination of drugs containing
      hydrogen peroxide for the preservation of high intratumoral oxygen concentration
      for 24 h following intratumoral injection with the agent. Based on the results,
      the clinical application of a novel enzyme-targeting radiosensitization
      treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC),
      was initiated for malignant tumors including advanced breast cancer, soft tissue
      sarcoma and cervical lymph node metastasis. Moreover, we have developed KORTUC
      III for locally advanced hepatocellular carcinoma and KORTUC IV for locally
      advanced pancreas cancer (stage IVa).

PMID- 22870107
TI  - Outcome of cephalic vein cut-down approach: A safe and feasible approach for
      totally implantable venous access device placement.
AB  - This study aimed to evaluate the safety and feasibility of the venous access via
      the cephalic vein cut-down (CVCD) approach for totally implantable venous access
      device (TIVAD) placements. A total of 79 patients who received TIVAD for the
      treatment of unresectable or recurrent colorectal carcinomas were recruited. The
      operation time and the complications were evaluated. Results showed the TIVAD
      placement via the CVCD approach was successful in 74 patients. A total of 5
      patients required conversion to a percutaneous puncture approach. The mean
      operation time was 34.7 min. No intraoperative or postoperative complications
      were observed. Therefore, the CVCD approach is a safe and feasible method for
      TIVAD placement.

PMID- 22870108
TI  - Novel disubstituted chrysene as a potent agent against colon cancer.
AB  - Research on polycyclic aromatic hydrocarbons and their derivatives has received
      significant attention from the scientific community. The present study involved
      the synthesis of several novel 6,12-disubstituted chrysene derivatives. Nitration
      of chrysene with nitric acid produced 6,12-dinitrochrysene which when reduced
      yielded 6,12-diaminochrysene. A coupling reaction of 6,12-diaminochrysene with an
      acid in the presence of isobutylchloroformate produced amide. The reduction of
      amide produced an amine. The amino was converted to a hydrochloride salt. The new
      compounds were characterized through different types of analytical data. One of
      these compounds demonstrated marked activity in vivo against a colon cancer cell
      line. Inhibition of the growth of this tumor was best noted at day 20 when each
      treatment regimen inhibited the average tumor volume by 50%. In a number of in
      vivo tests in various regimens, the hydrochloride salt demonstrated consistent
      inhibition of the growth of the cancer HT-29 cell line. Despite the research
      progress in polycyclic aromatic compounds, the use of these types of molecules as
      anticancer agents has not been reported systematically.

PMID- 22870109
TI  - Clinicopathological features and treatment sensitivity of elderly Chinese breast
      cancer patients.
AB  - This study aimed to determine the clinicopathological features and treatment
      sensitivity of elderly breast cancer patients in China. The clinical data of 594
      elderly breast cancer patients of 70 or more years of age were collected and
      compared to those of 657 patients of less than 70 years of age to analyze whether
      breast cancer in the elderly is different and whether the difference affected
      outcome. The median age was 75.2 years in the elderly patients and 49.8 years in
      the young patients. Age of menarche, parous status and body mass index were
      similar in the two groups. A higher frequency of steroid receptor-positive rate,
      a lower expression of HER-2 and p53, less axillary node-positive rate and earlier
      tumor stage were found in patients of 70 years or older. The 5-year relapse-free
      survival (RFS) and overall survival (OS) was 77 and 82% in the elderly and 86 and
      93% in the young patients, respectively. Patients with estrogen receptor (ER)
      positive or lymph node (LN)-negative cancers showed a more favorable outcome in
      the elderly patients. RFS and OS were increased in elderly patients who underwent
      endocrine therapy or omitted chemotherapy. Breast cancer in the elderly had more
      favorable tumor features, using estrogen receptor and lymph node status as
      prognostic factors. It was therefore concluded that adjuvant endocrine therapy
      may benefit elderly patients, while chemotherapy may not.

PMID- 22870110
TI  - Clinical significance and the correlation of expression between Let-7 and K-ras
      in non-small cell lung cancer.
AB  - To detect the expression levels of the lethal-7 (let-7) and K-ras genes in non
      small cell lung cancer (NSCLC) and investigate their significance, the expression
      of let-7 and K-ras was determined in cancerous tissues and pericancerous normal
      tissues of 31 NSCLC patients using reverse transcription-polymerase chain
      reaction. Our results using 31 NSCLC patient samples showed that 67.74% had a low
      let-7 expression (P<0.05), 64.52% had a high K-ras expression (P<0.05), and a
      significant correlation was observed between let-7 and K-ras gene expression (r=
      0.6336) in tumor tissues. Patients with a low let-7 expression had a
      significantly shorter survival than those with a moderate let-7 expression
      (P<0.05). Patients with a high K-ras expression also had a significantly shorter
      survival than those with a moderate K-ras expression (P<0.05). In conclusion, a
      low expression of let-7 and a high expression of K-ras are correlated with the
      pathogenesis and prognosis of NSCLC.

PMID- 22870111
TI  - Possibility of using mRNA expression levels for nucleic acid-metabolizing enzymes
      within prostate cancer cells as indices for prognostic factors.
AB  - Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine
      phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) are enzymes
      involved in nucleic acid metabolism. It has been reported (based on observations
      of various tumor types) that the extent of the mRNA expression of these enzymes
      within tumor tissues may be used as a factor to define tumor prognosis. It has
      also been reported that the mRNA expression patterns differ in each type of
      tumor. However, few reports are available on the distribution of mRNA expression
      in prostate cancers. This study was conducted on tissue specimens obtained from
      172 patients who were diagnosed with prostate cancer and had undergone total
      prostatectomies. The mRNA expression of TS, DPD, OPRT and TP was quantitatively
      analyzed using the Danenberg tumor profile (DTP) method. The results were used to
      examine the correlations between the distributions of the mRNAs and
      clinicopathological factors, as well as the significance of their expression as a
      prognostic factor. Patients with poorly differentiated cancers in their tissues
      showed a significant increase in the mRNA expression of TS and OPRT. The
      increases in the TP mRNA content were proportional to an increase in the Gleason
      scores. The prognosis was significantly poorer in those cases with a high
      expression of TS or OPRT mRNA and a low expression of DPD mRNA. In conclusion,
      the expression levels of mRNAs for TS, DPD and OPRT among the enzymes related to
      nucleic acid metabolism are useful as prognostic factors in patients with
      prostate cancers.

PMID- 22870112
TI  - Insulin-like growth factor-1 and childhood cancer risk.
AB  - Overexpression of growth factors and/or their receptors is a common event in
      malignancy and provides the underlying mechanisms for one of the hallmarks of
      cancer, uncontrolled proliferation. Mounting evidence suggests that IGF-1 is
      involved in the pathogenesis and progression of different types of human cancer
      such as colon, breast, prostate and lung. However, only a few studies have
      investigated the association between IGF-1 levels and childhood cancer risk. We
      aimed to compare the IGF-1 serum level in children with de novo malignancies to
      healthy children, and to assess its relationship with cancer type, stage,
      metastasis and different disease characteristics. The study was carried out on
      100 children; 50 children with de novo malignancies and 50 healthy children of
      matched age and gender as a control group. The patients were subjected to a
      routine work-up for their cancers according to our local standards. Estimation of
      the serum level of IGF-1 was carried out in the two groups using ELISA. Our
      results showed that children with cancer had significantly higher levels of IGF-1
      than healthy controls of the same age and gender. No association was found
      between IGF-1 and tumor type, stage, metastasis and other disease
      characteristics. In conclusion, the IGF-1 serum level is an important indicator
      of risk for the most prevalent forms of childhood cancer. It may be used to
      identify children at the highest risk for these cancers and aid in determing who
      may benefit most from preventive strategies. Given the small number of children
      in our study, studies with larger populations are required to confirm these
      results.

PMID- 22870113
TI  - Expression of alpha2,6-sialic acid-containing and Lewis-active glycolipids in
      several types of human ovarian carcinomas.
AB  - To identify glycolipid antigens associated with histologically defined types of
      ovarian carcinomas, we determined the amounts of alpha2,6-sialyl and Lewis-active
      glycolipids, the specific activities of the alpha2,3- and alpha2,6
      sialyltransferases, and the gene expression of sugar transferases in mucinous and
      serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma
      tissues and cell lines derived from them. alpha2,6-sialyl glycolipid
      IV(6)NeuAcalpha-nLc(4)Cer detected with a newly developed monoclonal antibody,
      Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher
      amounts than those in the other carcinoma tissues. On the other hand, the amounts
      of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than
      those in the other carcinoma tissues. No correlation was observed between the
      structures of Lewis glycolipids and the histological classification. The gene
      expression of alpha2,3- and alpha2,6-sialyltransferases and alpha1,3/4
      fucosyltransferase for the synthesis of Lewis-active glycolipids was not
      positively correlated with the amounts of the respective glycolipids, probably
      due to the epigenetic regulation of transferases in the overall metabolic
      pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with
      short carbohydrate chains correlated with the relative intensities of GM3 and GD3
      synthase gene expression, respectively. Among ovarian carcinoma-derived cell
      lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of
      Lewis-active glycolipid expression than the other carcinoma-derived ones, which
      was similar to that in the respective tissues. Thus, malignancy-related Lewis
      active glycolipids were shown to be regulated in different modes in ovarian
      serous cystadenocarcinomas and the other carcinomas.

PMID- 22870114
TI  - ERalpha and ERbeta expression in correlation with Ki-67, Bcl-2 and Bak in primary
      tumors and lymph node metastases of breast cancer: The effect of pre-operative
      chemotherapy.
AB  - This study aimed to assess the pre-operative chemotherapy impact on the
      relationship between estrogen receptor (ER) expression and markers of
      proliferation and apoptosis in primary and metastatic breast cancer.
      Immunohistochemical examinations were conducted on surgically removed ductal
      invasive breast cancers and their lymph node metastases in 135 patients. A total
      of 64 patients from this group underwent pre-operative chemotherapy and in 71
      cases the surgery was performed without primary chemotherapy. A negative
      correlation between ERalpha and Ki-67 was found in primary tumors and lymph node
      metastases. A positive correlation was observed between ERalpha and Bcl-2. A
      positive correlation was also noted between ERbeta and Bak, suggesting that the
      two ERs were involved in the regulation of proteins responsible for the control
      of the apoptotic process. Assessment of the expression of the proteins conducted
      separately in primary tumors and lymph node metastases did not reveal a
      significant effect of pre-operative chemotherapy on the correlations of ERs with
      Ki-67, Bcl-2 and Bak. However, the analysis of the correlations between the
      receptor expression in primary tumors and Ki-67, Bcl-2 and Bak in lymph node
      metastases showed a statistically significant impact of pre-operative
      chemotherapy on the correlations of ERalpha and Bcl-2 with ERbeta and Bak,
      confirming involvement of the two ERs in the regulation of apoptosis during
      breast carcinogenesis.

PMID- 22870115
TI  - Histopathologic subtype-specific genomic profiles of renal cell carcinomas
      identified by high-resolution whole-genome single nucleotide polymorphism array
      analysis.
AB  - To elucidate the novel and common genetic changes in histopathologic subtype
      specific profiles of renal cell carcinomas (RCCs), a newly developed high
      resolution whole-genome array analysis was applied. Human CNV370-Duo DNA Analysis
      BeadChip (genotype 370K) was used in a panel of 22 primary clear cell RCCs
      (ccRCCs), seven papillary RCCs (PRCCs) (six type II and one type I) and eight
      chromophobe RCCs (ChRCCs). In ccRCC, a chromosome 3p loss was identified in 95%
      of the carcinomas, suggesting that 3p loss is the first stage in ccRCC
      carcinogenesis. Other frequent changes included losses of 1p (23%), 3q (46%) and
      8p (32%), and gains of 5q (32%), 7p (27%), 7q (27%) and 1q (23%). The most
      frequent chromosomal losses in PRCC (43%) were noted in 3p and 3q, followed by
      29% of losses of 1p, 1q, 11q, 18q, 22p and 22q, and gains of 20q (57%), 20p
      (43%), 8q (43%) and 12q (43%). Loss of the entire chromosomes 1, 2, 6, 8, 10, 13
      or 17 was noted in patients with ChRCC. A high-density single nucleotide
      polymorphism array analysis confirmed that partial chromosomal changes rarely
      occur in ChRCC. Additionally, 32 microdeletions and 10 microamplifications of
      less than 1 Mb were detected, which may represent potential candidate tumor
      suppressor genes and oncogenes, respectively.

PMID- 22870116
TI  - Myoepithelial carcinoma of the parotid gland with bilateral thyroid involvement:
      A case report and review of the literature.
AB  - A patient was admitted to hospital with enlarged lobes of the thyroid gland with
      bilateral cervical lymph node involvement, and surgical excision followed.
      Histological examination of this specimen revealed a lesion that showed
      myoepithelial cell differentiation. Primary thyroid and skin appendage tumors
      were excluded based on clinical examination, conventional histology and
      immunohistochemistry. A tumor of the right parotid surgically treated in June
      2008, approximately 2 years previously, was originally classified as a basal cell
      adenocarcinoma with focal invasion, but was re-examined. Using
      immunohistochemistry, the parotid tumor was re-classified as a myoepithelial
      carcinoma. The thyroid tumor proved to be metastasis from a primary parotid
      tumor, which was not found in the updated review of the literature. The
      literature is reviewed, including current knowledge on the histological and
      immunohistochemical features of myoepithelial carcinoma, with limited data on
      treatment suggestions.

PMID- 22870117
TI  - Hepatocellular carcinoma patients highly and specifically expressing XAGE-1
      exhibit prolonged survival.
AB  - XAGE-1 is classified into the group of a new family of cancer-testis antigens
      (CTA) and has the four transcript variants of XAGE-1a, XAGE-1b, XAGE-1c and XAGE
      1d. Immunohistochemistry was used to investigate the expression of XAGE-1
      transcript variants in Chinese patients with hepatocellular carcinoma (HCC).
      Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR
      were used to analyze XAGE-1 gene expression, and XAGE-1 protein expression was
      examined by immunohistochemistry. Furthermore, the clinical correlation of XAGE-1
      expression was analyzed. The expression of the XAGE-1 mRNA was investigated in
      the tissues of 96 HCC patients and all XAGE-1 isoforms were detected in these
      tissues. Three types of XAGE-1 transcript variants (XAGE-1b, XAGE-1c and XAGE-1d)
      showed high specific and frequent expression in HCC tissues, with the positive
      expression rate of XAGE-1b, XAGE-1c and XAGE-1d being 41.7% (40/96), 15.6%
      (15/96) and 26.0% (25/96), respectively. XAGE-1b was the dominant type, but none
      of the three were detected in adjacent non-HCC tissues. Only 2 cases of XAGE-1a
      mRNA expression were observed. Moreover, XAGE-1 protein was detected in 39 of 96
      HCC patients, but none in the adjacent non-cancerous tissue and normal liver
      tissue. No relationship was found between the expression of XAGE-1 and clinical
      parameters, such as age, gender, tumor size, TNM staging, serum AFP level and
      infection with hepatitis virus. Patients with XAGE-1b-positive transcript variant
      exhibited shorter 2-year survival times. The high frequency and specificity of
      XAGE-1, particularly XAGE-1b, in HCC indicates that their products may predict
      the prognosis of HCC patients and be novel targets for antigen-specific
      immunotherapy to HCC.

PMID- 22870118
TI  - Neutrophil gelatinase-associated lipocalin immunoexpression in colorectal
      carcinoma: A stage-specific prognostic factor?
AB  - TNM post-surgical staging is considered to be one of the most powerful
      prognosticators for colorectal carcinoma. Although patient survival mostly
      decreases concomitantly to stage increase, in a percentage of cases TNM stage
      appears only to express the anatomic extent of the neoplasia with no correlation
      with clinical outcome. Thus, the identification of additional prognostic markers
      for colorectal cancer is required. Neutrophil gelatinase-associated lipocalin
      (NGAL) is a 25-kDa protein that appears to play an important role in colorectal
      cancer progression. In order to evaluate whether NGAL expression may be
      considered as a predictor of colorectal cancer progression, we analyzed its
      correlation with clinicopathological characteristics, as well as with patient
      progression-free survival in a series of surgically resected colorectal
      carcinomas. A variable NGAL immunoexpression was found in 24 out of the 64
      analyzed cases. When only the positive cases were considered, a significant
      association was found between a high NGAL expression and the presence of distant
      metastases or high tumor stage. In addition, the presence of NGAL was a
      significant negative prognostic marker correlated with a shorter progression-free
      survival in stage I colorectal carcinoma, but not in the remaining TNM stages. If
      our findings are confirmed in more extensive analyses on stage I colorectal
      carcinoma, NGAL assessment may be used in order to select those patients with a
      higher progression risk and to submit them to adjuvant therapies useful to
      prevent adverse outcome.

PMID- 22870119
TI  - Prediction and analysis of HLA-A2/A24-restricted cytotoxic T-lymphocyte epitopes
      of the tumor antigen MAGE-n using the artificial neural networks method on
      NetCTL1.2 Server.
AB  - Cancer immunotherapy has become one of the most important therapeutic approaches
      to cancer in the past two decades. Tumor antigen-derived peptides have been
      widely used to elicit tumor-specific cytotoxic T lymphocytes (CTLs). Antigen
      specific CTLs induced by MAGE-derived peptides have proven to be highly
      efficacious in the prevention and treatment of various types of tumor. MAGE-n is
      a new member of the MAGE gene family and has been shown to be closely associated
      with hepatocellular carcinoma. It is highly homologous to the MAGE-A gene
      subfamily, particularly to MAGE-3 (93%). MAGE-n-derived peptide QLVFGIEVV is a
      novel HLA-A2.1-restricted CTL epitope that induces MAGE-n-specific CTLs in vitro.
      Identification of these CTL epitopes may lead to clinical applications of these
      peptides as cancer vaccines for patients with MAGE-n(+)/HLA-A2(+) tumors. In the
      present study, HLA-A/A24-restricted CTL epitopes of antigen MAGE-n were predicted
      using the NetCTL1.2 Server on the web, COMB >0.85. The results showed that the
      NetCTL1.2 Server prediction method improved prediction efficacy and accuracy.
      Additionally, 8 HLA-A2- and 9 HLA-A24-restricted CTL epitope candidates
      (nonamers) derived from the tumor antigen MAGE-n were predicted. These nonamers,
      following identification via experimentation, may contribute to the development
      of potential antigen peptide tumor vaccines.

PMID- 22870120
TI  - Melanoma leptomeningeal dissemination following frontoparietal metastasis
      surgery: Case report and review of the literature.
AB  - We present the case of a patient with a solitary left frontoparietal brain
      metastasis of melanoma previously treated with surgery. Three months later, the
      patient was admitted to the emergency room in a confusional state with meningeal
      signs. A cerebrospinal fluid (CSF) test and magnetic resonance imaging findings
      suggested a subarachnoid haemorrhage (SAH) and/or meningeal carcinomatosis. The
      results of a cytological examination of the CSF showed neoplastic epithelial
      cells consistent with metastatic melanoma cells. Resection of metastatic
      posterior fossa lesions is often cited as a risk factor for leptomeningeal
      dissemination, however, when the resection is limited to the anterior fossa, this
      complication is relatively rare. In contrast, SAH may be a complication of
      leptomeningeal dissemination and responsible for acute meningeal syndrome.
      Treatment with high doses of corticoids did not show any improvement, and
      intrathecal chemotherapy was not possible due to the patient's poor functional
      status. She succumbed 1 week after admission.

PMID- 22870121
TI  - Metastatic colorectal cancer in the elderly: An overview of the systemic
      treatment modalities (Review).
AB  - Colorectal cancer (CRC) is one of the most frequently occurring types of cancer.
      Worldwide, more than 800,000 new cases of CRC are diagnosed each year. The median
      ages at CRC diagnosis and death are 71 and 75 years, respectively. The majority
      ot patients (50-60%) with colorectal cancer are diagnosed at stage IV disease.
      Patients aged 65 or older are characterized by a higher incidence of significant
      co-morbidities, decreased regenerative capacity of bone marrow and worse general
      performance. Anti-neoplastic therapies used for the treatment of colorectal
      cancer include irinotecan, oxaliplatin, 5-fluorouracil, leucovorin, capecitabine
      and monoclonal antibodies. Analysis of the efficacy of the presented
      chemotherapeutic and chemoimmunotherapeutic regimens in the treatment of
      metastatic CRC in patients older than 65 and 70 years compared to 'younger'
      patients, generally demonstrated comparable efficacy, time to disease progression
      and overall survival. Age criterion should not be considered when assessing the
      eligibility of patients with metastatic CRC for treatment of the above-mentioned
      chemotherapeutic and chemoimmunotherapeutic regimens. Treatment should be
      individualized based on the potential risks and benefits anticipated for each
      patient.

PMID- 22870122
TI  - Enhanced antitumor effect of combination intravesical mitomycin C and bacillus
      Calmette-Guerin therapy in an orthotopic bladder cancer model.
AB  - Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the
      most successful adjuvant agent for the treatment and/or prophylaxis of non-muscle
      invasive bladder cancer (NMIBC). However, NMIBCs recur in 60-70% of cases and 30%
      of these recurrent tumors present with a higher grade and more invasive
      properties. Patients that do not respond to intravesical BCG therapy are
      considered to be a challenge for urologists. Thus, novel conservative
      possibilities should be explored. To test the efficacy of a novel therapeutic
      approach, we examined the antitumor effect of combination therapy by intravesical
      administration of mitomycin C (MMC) plus BCG, infusing the two drugs
      simultaneously, in an orthotopic bladder cancer model. Intravesical BCG and MMC
      administration showed a dose-dependent survival (n=8 per group). The combination
      of MMC and BCG provided a significant survival advantage compared to the BCG
      alone (p=0.035) and MMC-alone groups (p=0.040) (n=8 per group). The group with
      combined MMC/BCG exhibited a survival period similar to that achieved with an
      amount eight times higher that of BCG (n=10 per group). Ki-67 labeling index of
      cancer cells, showing tumor proliferation, was significantly lower in the
      combined group compared to the BCG-alone (p<0.05), MMC-alone (p<0.01) and control
      groups (p<0.01). No difference was detected between the combined group and the
      BCG-alone group with regard to CD3, T-cell infiltration and CD68 macrophage
      activity. The combined MMC/BCG treatment decreased the tumor appearance rate,
      improved the survival period and reduced the cellular proliferation rate in
      tumors compared to the BCG-alone treatment. The results suggest that the combined
      intravesical MMC/BCG treatment induced an enhanced antitumor effect against
      bladder tumors. The combined MMC/BCG treatment also showed a survival period
      similar to that achieved using a dose eight times higher of BCG-alone.

PMID- 22870123
TI  - Clinical significance of GLUT-1 expression in patients with esophageal cancer
      treated with concurrent chemoradiotherapy.
AB  - This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression
      in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in
      patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A
      total of 25 patients with esophageal cancer treated with concurrent CRT were
      reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median
      66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin
      (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used
      concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses.
      Tissue samples from esophageal carcinoma were obtained from the 25 patients by
      biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1
      expression was performed using immunohistochemical staining. High GLUT-1
      expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was
      significantly correlated with clinical T stage (p=0.0454), clinical N stage
      (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1
      expression had significantly poorer local control (LC) (5-year LC 28.6%) than
      those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis
      revealed that GLUT-1 and the number of chemotherapy courses were independent
      prognostic factors for LC. Patients with a high GLUT-1 expression had
      significantly lower recurrence-free survival (RFS) compared to those with a low
      GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the
      number of chemotherapy courses and clinical M stage were independent prognostic
      factors for RFS. GLUT-1 expression was significantly correlated with clinical T
      stage, clinical N stage and initial response to concurrent CRT, and was
      predictive of LC and RFS for patients with esophageal cancer treated with
      concurrent CRT.

PMID- 22870125
TI  - Pituicytoma: Report of two cases.
AB  - This report describes two cases of pituicytoma. The two patients were female and
      presented with visual complaints, diabetes insipidus, headaches and menstrual
      disorders. The imaging characteristic was an intrasellar or suprasellar mass, and
      one mass originated in the pituitary stalk. The mass showed homogeneous
      enhancement with contrast administration. A hematoxylin and eosin stain showed a
      compact structure consisting of elongated, bipolar spindle cells arranged in
      interlacing fascicles or assuming a storiform pattern. Immunohistochemically, the
      tumor showed diffuse strong expression of S-100 protein, vimentin and epithelial
      membrane antigen, and glial fibrillary acidic protein was focally positive. The
      pituicytoma may have originated in the pituitary stalk and presented with
      diabetes insipidus, and the differential diagnosis should be compared with the
      pituitary stalk mass. Bleeding during resection was moderate, and surgery was
      regarded as the first choice of treatment for pituicytomas.

PMID- 22870124
TI  - Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA
      induced mammary tumor development.
AB  - Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk
      factors in the development of breast cancer. We investigated the long-term
      effects of high-isoflavone soy intake and obesity on 7,12
      dimethylbenz(a)anthracene (DMBA)-induced mammary tumor development and on serum
      IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed
      casein or high-isoflavone soy protein were orally gavaged at age 50 days with
      DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%)
      developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the
      obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of
      obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the
      lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days,
      soy- and obese casein-fed rats exhibited increased serum IGF-1 compared to the
      lean rats and this increase was maintained for the rest of the experiment
      (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001).
      However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels
      compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3
      levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3
      levels were increased in obese casein-and soy-fed rats (P<0.001). The results
      suggest that female Zucker rats fed casein diets are protected against DMBA
      induced mammary tumors, which is not the case for those on high-isoflavone soy
      diet, and changes in the concentration of serum IGFBP-3 may contribute to the
      incidence of DMBA-induced mammary tumors.

PMID- 22870126
TI  - Apigenin suppresses the growth of colorectal cancer xenografts via
      phosphorylation and up-regulated FADD expression.
AB  - Apigenin is a flavonoid belonging to the flavone structural class. It has been
      implicated as a chemopreventive agent against prostate and breast cancers.
      However, to the best of our knowledge, no published data are available regarding
      apigenin in colorectal cancer (CRC). The effects and mechanisms of apigenin on
      CRC may vary significantly. This study aimed to analyze the effects of apigenin
      on the growth of CRC xenografts in nude mice derived from SW480, as well as to
      investigate the underlying mechanisms. Whole-body fluorescence imaging is an
      inexpensive optical system used to visualize gene expression in small mammals
      using reporter genes, such as eGFP as a reporter. In our study, the expression of
      eGFP may reflect the size of the tumor. A terminal deoxynucleotidyl transferase
      dUTP nick end-labeling (TUNEL) assay showed that apigenin promoted the apoptosis
      of CRC cells. Furthermore, the expression of five genes related to the
      proliferation and apoptosis of CRC, i.e., cyclin D1, BAG-1, Bcl-2, yrdC and Fas
      associated protein with death domain (FADD), was detected by real-time
      quantitative RT-PCR. Among these genes, the up-regulated expression of FADD was
      noted in CRC xenograft tumors treated with apigenin. Immunohistochemistry and
      Western blotting confirmed the results at the protein level. Furthermore, Western
      blot analysis showed that apigenin induced the phosphorylation of FADD. Our
      findings suggest that apigenin enhances the expression of FADD and induces its
      phosphorylation, which may cause apoptosis of CRC cells and inhibition of tumor
      growth.

PMID- 22870127
TI  - Medullary thyroid carcinoma: The third most common thyroid cancer reviewed.
AB  - Medullary thyroid cancer is a type of thyroid cancer of neuroendocrine origin. It
      occurs in hereditary and sporadic forms, and its aggressive behavior is
      associated with the clinical presentation and type of RET mutation. Total
      thyroidectomy remains the ideal choice of treatment. Early diagnosis and
      treatment are the fundamental for a 100% cure rate. In this study, we present our
      experience of 3 cases, along with a complete review of the literature derived
      from a Pubmed Database search.

PMID- 22870128
TI  - IgM multiple myeloma presenting with bleeding tendency: a case report with
      immunophenotype analysis.
AB  - IgM multiple myeloma (MM) is an extremely rare lymphoproliferative disease
      associated with an aggressive clinical course. However, the diagnosis of IgM MM
      may be complicated by Waldenstrom's macroglobulinemia (WM), particularly when
      clinical manifestations and morphological features are not typical. It is crucial
      to distinguish between IgM MM and WM as their prognoses and treatment strategies
      are different. We report a case of IgM MM presenting with bleeding tendency and
      an immunophenotype analysis using flow cytometry and immunohistochemistry. Bone
      marrow cells exhibited a typical phenotype for plasma cells, expressing
      monoclonal cytoplasmatic IgL-lambda, CD38 and CD138 instead of pan-B cell
      antigens CD19, CD20 and CD22, which are characteristic of the typical
      immunophenotype of WM. Therefore, the diagnosis of IgM MM was confirmed in this
      case, highlighting the significance of detailed immuno-phenotypic evaluation when
      clinical and morphological features are atypical.

PMID- 22870129
TI  - Utility of BRAF protein overexpression in predicting the metastasis potential of
      papillary thyroid carcinoma.
AB  - V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a significant member of
      the MAPK pathway, the point mutation (V600E) of which is a common genetic event
      in papillary thyroid carcinoma (PTC). Investigators showed that the variations in
      BRAF expression levels were independent of the V600E mutation. These variations
      were involved in the pathogenesis of thyroid carcinomas. This study evaluated the
      feasibility of BRAF, proliferating cell nuclear antigen (PCNA) and hMSH2 as
      markers for the prediction of the metastatic potential of PTC. Using
      immunohistochemistry, the expression of BRAF, PCNA and hMSH2 proteins was studied
      in 70 PTC and 29 nodular goiter (NG) tissues. The results indicated that i) the
      positive rate of BRAF, PCNA and hMSH2 expression in PTCs was significantly higher
      than that in NGs (P=0.000, P=0.000 and P=0.003, respectively), ii) the positive
      rate of BRAF expression in the lymph node metastasis (LNM) group was
      significantly higher than that in the non-LNM group (P=0.019), iii) the age at
      diagnosis of PTC patients with LNM was significantly older compared to that
      without LNM (P=0.021) and iv) the positive rate of BRAF expression significantly
      correlated with that of PCNA and hMSH2 expression (P=0.000 and P=0.019,
      respectively). In conclusion, BRAF, PCNA and hMSH2 overexpression appeared to be
      molecular events of PTC carcinogenesis. Older patients with BRAF overexpression
      appear to be a high-risk group for PTC metastasis. Detection of BRAF expression
      is likely to aid in the prediction of the metastatic potential of the carcinoma.

PMID- 22870130
TI  - Human papillomavirus infection induces NF-kappaB activation in cervical cancer: A
      comparison with penile cancer.
AB  - This study aimed to determine the relationship between human papillomavirus (HPV)
      and nuclear factor-kappaB (NF-kappaB) in cervical cancer using 62 tissues of
      cervical cancer, and to compare the findings to penile cancer. HPV-DNA
      integration is a crucial factor for malignant transformation in cervical cancer
      and can be identified using in situ hybridization. Of the 62 cases, HPV infection
      was detected in 28 (45.2%). This frequency was lower than in penile cancer
      (68.2%) as shown by our previous study. The earliest age of onset of cervical and
      penile cancer was 18 and 35, respectively, whereas the mean age of the initial
      diagnosis of cervical and penile cancer was 50.1 and 59.6, respectively. The
      discrepancies of HPV prevalence, earliest ages of onset and mean ages between
      cervical and penile cancer patients may result from the gender-based synergistic
      action of HPV associated with multiple epidemiological co-factors. Of the 28 HPV
      infected cases, NF-kappaB expression was observed in the nucleus in 18 (64.3%),
      in the cytoplasm in 19 (67.9%) and in the nucleus and/or cytoplasm in 27 cases
      (96.4%). The overexpression of NF-kappaB in cervical cancer cases suggests that
      NF-kappaB activation is a key modulator in driving chronic inflammation to
      cancer.

PMID- 22870131
TI  - Soluble VEGF receptor-2 may be a predictive marker of anti-angiogenic therapy
      with clinically available safe agents.
AB  - The identification of biomarkers of anti-angiogenic therapy that predict clinical
      benefit is of vital importance. We previously reported that a combination
      treatment with clinically available safe agents, specifically angiotensin
      converting enzyme inhibitor (ACE-I) and vitamin K (VK), inhibited the cumulative
      recurrence of hepatocellular carcinoma (HCC) via suppression of the vascular
      endothelial growth factor (VEGF). The present study aimed to identify non
      invasive biological markers that predict the clinically beneficial effect of this
      combination regimen. A combination of ACE-I (perindopril; 4 mg/day) and VK
      (menatetrenone; 45 mg/day) was administered for 54 months following curative
      therapy for HCC. The cumulative recurrence and several indices, which are
      reportedly considered as biological markers of anti-angiogenic therapies, were
      analyzed. The combined treatment of ACE-I and VK markedly inhibited the
      cumulative recurrence of HCC during the 54-month follow-up. The serum VEGF and
      soluble VEGF receptor (sVEGFR)-2 were significantly suppressed with this
      combination regimen, whereas sVEGFR-1 was not. In HCC patients without
      recurrence, a significant suppression of VEGF and sVEGFR-2 was achieved within 6
      and 3 months after treatment, respectively. In conclusion, the combination
      treatment of ACE-I and VK is a potentially novel anti-angiogenic strategy for
      secondary chemoprevention against HCC since the two agents are widely used in
      clinical practice without serious side effects. Furthermore, sVEGFR-2 may become
      a useful clinical predictive marker of this combination treatment.

PMID- 22870132
TI  - Extraskeletal subcutaneous osteosarcoma of the upper arm: A case report.
AB  - Extraskeletal osteosarcoma (ESOS) occurs in approximately 1% of soft tissue
      sarcomas and 2-4% of all osteosarcomas. In particular, subcutaneous osteosarcoma
      is extremely rare, occurring in less than 10% of ESOS cases. This report presents
      a case of a subcutaneous tumor in the upper arm of a 79-year-old male. Imaging
      and pathological findings led to the conclusion that the soft tissue tumor should
      be diagnosed as subcutaneous osteosarcoma. Additionally, this case report
      documented the clinicopathological findings of the extraskeletal subcutaneous
      osteosarcoma in this case and discussed its clinical features by reviewing cases
      previously described in the literature.

PMID- 22870133
TI  - Phenotype of tumor lymphatic vessels is a prognostic factor in human tongue
      squamous cell carcinoma.
AB  - Tumor metastasis to lymph nodes occurs through the lymphatic vessels located in
      the tumor circumference. However, few studies have focused on the phenotypes of
      lymphatic vessels around these tumors. We investigated the characteristics of the
      lymph vessels of tongue squamous cell carcinoma (SCC) and compared them to
      clinicopathological characteristics. A total of 43 patients diagnosed as having
      tongue SCC consulted Hokkaido University Hospital were examined. The lymphatic
      vessels were identified by antibody D2-40 and the number and diameter of tumor
      lymphatic vessels were measured. The proliferative activity of lymphatic
      endothelial cells was also examined by immunostaining using antibody MIB-1. We
      then measured the DNA density of lymphatic endothelial cells in normal and tumor
      tissues. The number of tumor lymphatic vessels significantly increased in highly
      metastatic cases of tongue SCC, particularly in cases with a large number of
      micro lymphatic vessels. A significant correlation was found between the
      metastatic and proliferative activity of tumor lymphatic endothelial cells.
      Moreover, the DNA density of tumor lymphatic endothelial cells increased compared
      to normal tissues. These results suggest that the phenotypes of tumor lymphatic
      endothelial cells are an indicator of lymph node metastasis of tongue SCC.

PMID- 22870134
TI  - Radiation recall dermatitis due to gemcitabine does not suggest the need to
      discontinue chemotherapy.
AB  - Radiation recall is common following treatment with certain chemotherapy drugs
      and presents frequently as a skin reaction. With gemcitabine, such a recall
      phenomenon may affect internal tissues and presents itself as myositis. Although
      such reactions have previously been reported in the literature, whether or not to
      continue chemotherapy during such reactions remains controversial. We reported a
      case of radiation recall in a patient treated with gemcitabine and radiation
      therapy that presented as myositis. We were able to continue palliative
      chemotherapy and manage the side effects with supportive care treatment. This
      case report provides partial support for the continuation of chemotherapy when
      required even when a recall reaction is encountered.

PMID- 22870135
TI  - Isolation and characterization of erlotinib-resistant human non-small cell lung
      cancer A549 cells.
AB  - Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,
      is an effective therapy for non-small cell lung cancer (NSCLC). However,
      resistance to erlotinib reduces its efficacy. To investigate the basis of
      erlotinib resistance, we isolated erlotinib-resistant human NSCLC A549 cells,
      termed A549/ER cells. The A549/ER cells were found to be resistant to erlotinib,
      as well as paclitaxel and gemcitabine. We then performed a PCR array to
      investigate the resistance to erlotinib in A549/ER cells. EGFR expression in
      A549/ER cells was decreased compared to A549 cells. The expression of fibroblast
      growth factor 2 (FGF2) and p21 in A549/ER was increased when compared to A549
      cells. Our results suggest that the down-regulation of EGFR and up-regulation of
      FGF2 is related to resistance to erlotinib in A549/ER cells.

PMID- 22870136
TI  - Detection of fecal interferon-induced transmembrane protein messenger RNA for
      colorectal cancer screening.
AB  - Interferon-induced transmembrane protein (IFITM) is reported to be frequently
      overexpressed in colorectal tumors. This study aimed to determine the usefulness
      of detecting fecal IFITM messenger RNA (mRNA) by real-time reverse-transcription
      polymerase chain reaction (RT-PCR) for colorectal cancer (CRC) screening. This
      pilot study included 21 patients with CRC and 23 healthy controls. Total RNA was
      isolated from the feces of the patients, and the expression levels of the mRNA of
      IFITM1, IFITM2 and IFITM3 were measured by real-time RT-PCR to detect CRC.
      Receiver operating characteristic curves of respective genes were generated, and
      the area under the curve (AUC), sensitivity and specificity were determined. When
      the 44 patients were analyzed, the AUCs of fecal IFITM1, IFITM2 and IFITM3
      expression analysis were 0.82, 0.80 and 0.65, respectively. The sensitivities
      were 67% [14/21; 95% confidence interval (CI) 43-85%], 67% (14/21; 95% CI 43-85%)
      and 71% (15/21; 95% CI 48-89%), respectively; and the specificities were 96%
      (1/23; 95% CI 78-100%), 96% (1/23; 95% CI 78-100%) and 61% (9/23; 95% CI 39-80%),
      respectively. When IFITM1 and IFITM2 were combined, the sensitivity was 86%
      (18/21; 95% CI 64-97%) and the specificity was 96% (1/23; 95% CI 78-100%). The
      fecal expression analysis of IFITM1 and IFITM2 mRNA by real-time RT-PCR for CRC
      screening exhibited high specificities, and the sensitivity was further improved
      by combining IFITM1 and IFITM2.

PMID- 22870137
TI  - Zeranol may increase the risk of leptin-induced neoplasia in human breast.
AB  - Breast cancer and obesity are serious health problems and their relationship has
      been studied for many years. Leptin is mainly secreted by adipocytes and plays a
      key role in breast cancer development. Leptin expression is up-regulated in obese
      individuals and promotes breast cancer cell growth. On the other hand, exposure
      to environmental estrogens has been found to be directly related to breast
      cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter used in the beef
      industry in the US. This study focused on the evaluation of Z and Z-containing
      sera (ZS) and its adverse health risk to human consumption of Z-containing meat
      produced from Z-implanted beef cattle. We hypothesized that Z increases the risk
      of breast neoplasia in women, particularly in obese women. A cell proliferation
      assay, ELISA analysis, RT-PCR and Western blot analysis were conducted. Our study
      demonstrated that Z and ZS collected from Z-implanted heifers stimulated the
      proliferation of primary cultured human normal breast epithelial cells (HNBECs)
      by up-regulating cyclin D1 expression. Leptin increased the sensitivity of HNBECs
      to Z, and Z increased the ability of HNBECs to secrete leptin. These results
      suggest an interaction between leptin and Z in HNBECs. Furthermore, Z may play a
      role in leptin-induced breast neoplasia.

PMID- 22870138
TI  - Osteopontin is a tumor autoantigen in prostate cancer patients.
AB  - Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate
      cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to
      the progression of the disease. This study aimed to evaluate whether OPN evokes a
      humoral immune response in PCa patients and whether the reactivity levels of anti
      OPN antibodies may be used to better differentiate PCa from benign and healthy
      donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign
      prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested
      by immunoblots using the recombinant human OPN. The frequency of anti-OPN
      antibodies was significantly higher in PCa (66%) plasma samples as compared to
      BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high
      proportion of plasma samples from patients with a Gleason score of less than 6
      (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ
      confined disease (70%), suggesting that anti-OPN antibodies may be used as an
      early serum marker for PCa. To the best of our knowledge, this is the first
      description of OPN as a tumor autoantigen and one of the most reactive individual
      autoantigens described thus far. These data support the inclusion of OPN in a
      multiplex of tumor antigens in order to perform antibody profiling in PCa as well
      as in other malignancies overexpressing OPN.

PMID- 22870139
TI  - Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant
      human glioma cells.
AB  - The alkylating agent temozolomide (TMZ) is an effective drug used for the
      treatment of malignant gliomas. However, tumor relapse combined with the
      development of drug resistance remains a significant problem. To clarify the
      mechanism of the resistance of glioma cells to TMZ chemotherapy, TMZ-resistant
      glioma cell lines (TR cells) were generated using U373 and U251 human glioma
      cells, and TMZ-resistance was confirmed via viability and apoptosis assays. The
      TMZ-resistance of TR cells was not associated with the TMZ-resistance molecule
      O(6)-methylguanine-DNA-methyltransferase. Notably, the expression level of signal
      transducers and activators of transcription 3 (STAT3) and serine 727
      phosphorylated STAT3 (pSTAT3-Ser727) was highly increased in TR cells, while that
      of 705-phosphorylated STAT3 (pSTAT3-Tyr705) was decreased. The inhibition of
      STAT3 expression by small interfering RNA enhanced TR cell TMZ sensitivity. These
      results suggest that STAT3 contributes to TMZ-resistance in gliomas and is a
      potential target for the reversal of TMZ-resistance in patients with a recurrent
      glioma.

PMID- 22870140
TI  - Nordihydroguaiaretic acid inhibits growth of cervical cancer SiHa cells by up
      regulating p21.
AB  - Nordihydroguaiaretic acid (NDGA) and its derivatives possess anti-cancer effects
      on various types of cancer via the induction of apoptosis or cell cycle arrest.
      This study proved that NDGA inhibited cervical cancer SiHa cell growth and
      induced cell cycle arrest at the G(1) phase, which may be a consequence of cell
      cycle kinase inhibitor p21 induction. NDGA promoted acetylation of histone H3 in
      total and p21 gene-associated chromatin. This effect is gene selective, since
      NDGA has no impact on the p27 gene. NDGA also inhibited HPV-16 E6 gene
      transcription, which in turn resulted in the restoration of p53 protein levels.
      The silencing mediator for retinoid and thyroid hormone receptors (SMRT) is a key
      component of the HDAC3-HDAC4-N-CoR/SMRT complex. We found that NDGA significantly
      inhibited the transcription of SMRT, which, together with p53, may aid in the
      detection of the increase of histone H3 acetylation within the p21 gene. Our
      results suggest that NDGA induces p21 transcription by selectively elevating
      histone H3 acetylation associated with p21 gene and p53 protein levels via the
      inhibition of HPV-16 E6 expression.

PMID- 22870141
TI  - Rhein lysinate inhibits cell growth by modulating various mitogen-activated
      protein kinases in cervical cancer cells.
AB  - In previous studies, we found that rhein lysinate (RHL; the salt of rhein and
      lysine, easily dissolved in water) inhibited the growth of tumor cells in breast
      and ovarian cancer and hepatocellular carcinoma. This study aimed to investigate
      the effect of RHL on the growth of human cervical carcinoma HeLa cells and any
      underlying mechanisms. RHL inhibited the growth of HeLa cells in a dose- and time
      dependent manner. It was also noted that RHL induced apoptosis in HeLa cells in a
      dose-dependent manner. Mechanistically, RHL triggered HeLa cell apoptosis by
      increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase
      3/7. In addition, the activation of p38 mitogen-activated protein kinase (MAPK)
      and c-Jun NH2-terminal kinase (JNK) was a critical mediator in RHL-induced growth
      inhibition. Inhibition of the expression of p38 MAPK and JNK by pharmacological
      inhibitors reversed RHL-induced growth inhibition by decreasing the level of
      cleaved PARP and caspase-3/7. Phosphorylation of the extracellular signal-related
      kinase (ERK) was increased by RHL; conversely, the MEK inhibitor which inhibits
      ERK activity, synergistically enhanced RHL-induced growth inhibition in HeLa
      cells. The results showed that RHL inhibits Hela cell growth through the
      activation of p38 MAPK and JNK, and is a potential chemotherapeutic agent for
      cervical cancer.

PMID- 22870142
TI  - Cribriform adenocarcinoma of the base of the tongue and low-grade, polymorphic
      adenocarcinomas of the salivary glands.
AB  - Low-grade, polymorphic adenocarcinomas occur mainly in females and are usually
      associated with the small salivary glands of the palate. The tumors are
      malignant, but not aggressive. Regional neck as well as distant metastasis is
      rare and the mortality rate is low. Cribriform adenocarcinoma of the salivary
      glands is a rare tumor, currently ranked among low-grade, polymorphic
      adenocarcinomas of the salivary glands. However, it differs from carcinomas in
      this group as it metastasizes to the cervical lymph nodes and exhibits frequent
      primary localization in the small salivary glands at the base of the tongue.
      Despite the tendency to metastasize, patient prognosis remains favorable. A case
      of a 72-year-old woman with neck metastases of cribriform adenocarcinoma, of
      unknown primary origin, is reported. The primary tumor origin was ultimately
      determined using nuclear magnetic resonance, histological verification was
      difficult due to the presence of an intact mucosal cover over the tumor.
      Cribriform adenocarcinoma is known to have a number of characteristics in common
      with a typical low-grade, salivary gland adenocarcinoma. However, in contrast to
      low-grade adenocarcinomas, the tumor presented with neck lymph node metastasis.

PMID- 22870143
TI  - Early chemosensitivity of normal hematopoietic cells and malignant lymphoblasts
      predicts relapse in childhood acute lymphoblastic leukemia.
AB  - For the last 30 years, numerous clinical and biological pretreatment risk factors
      have been utilized for risk-based treatment assignment in childhood acute
      lymphoblastic leukemia (ALL). However, with improved chemotherapy regimens, many
      of these traditional prognostic factors have lost clinical significance. We aimed
      to improve relapse prediction in children with ALL through evaluation of the
      early chemosensitivity of normal and malignant cells and to determine the
      relationship between such chemosensitivity and risk of relapse. We
      retrospectively analyzed a cohort of 60 children with newly diagnosed ALL of whom
      40 patients were in complete remission for at least 4 years and 20 patients
      relapsed during or following treatment. Time to peripheral blood blast clearance
      (PBBC) was used as a measure of chemosensitivity of malignant lymphoblasts while
      end-of-induction complete blood count (CBC) parameters were used as a measure of
      chemosensitivity of normal hematopoietic cells. Our results showed that longer
      time to PBBC and lower end-of-induction total leukocyte count (TLC) and absolute
      neutrophil count (ANC) were significantly associated with increased risk of
      relapse. In conclusion, time to PBBC and end-of-induction TLC and ANC are
      important predictors of relapse and should be used to modify the intensity of
      chemotherapy at earlier time points during the course of treatment. A wider
      prospective, randomized, controlled trial is required to confirm our results.

PMID- 22870144
TI  - Dietary D-glucarate effects on the biomarkers of inflammation during early post
      initiation stages of benzo[a]pyrene-induced lung tumorigenesis in A/J mice.
AB  - Previous studies showed that dietary calcium D-glucarate (CG) inhibited
      benzo[a]pyrene (B[a]P)-induced A/J mouse lung tumorigenesis, suppressing cell
      proliferation and chronic inflammation and inducing apoptosis during late post
      initiation stages. The present study aimed to investigate changes in the
      homeostasis of cytokines in blood serum, as well as alterations in biomarkers of
      inflammation and apoptosis in lung tissue caused by dietary CG during early post
      initiation stages of B[a]P-induced lung tumorigenesis. Two doses of 3 mg of B[a]P
      were given intragastrically to A/J mice 2 weeks apart. CG administration in the
      AIN-93G diet (2 and 4%, w/w) commenced at 2 weeks following the second dose of
      B[a]P. The levels of interleukin (IL)-6, IL-10 and tumor necrosis factor alpha
      (TNFalpha) in blood serum were investigated by FCAP array analysis. Two weeks
      after the second dose of B[a]P, approximately 8- and 28-fold increases of
      TNFalpha and IL-6, respectively, occurred in the blood serum and an approximately
      16% decrease of IL-10 levels compared to the untreated control group was noted.
      At 4 weeks after the second dose of B[a]P and after 2 weeks of CG administration
      in the diet, the 2 and 4% CG diets significantly reduced the levels of IL-6 and
      TNFalpha (by 70 and 33%, respectively). In a dose-related manner, the diets also
      increased the level of anti-inflammatory cytokine IL-10 compared to the B[a]P
      group. At 6 weeks after the second dose of B[a]P, the cytokine levels in the
      serum continued to show a decrease in the CG-treated groups. These events are
      accompanied by an increased level of cleaved caspase-9 product with a molecular
      weight of 37 kDa. In conclusion, dietary D-glucarate decreases the level of
      proinflammatory cytokines, increases the level of the anti-inflammatory cytokine
      IL-10 during early post-initiation stages of B[a]P-induced lung tumorigenesis in
      A/J mice and affects apoptotic induction.

PMID- 22870145
TI  - XPD Lys751Gln increases the risk of breast cancer.
AB  - Breast cancer incidence has been on the increase in south Indian women.
      Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD
      (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision
      repair and transcription coupled repair, may affect an individual's DNA repair
      capacity, particularly that of bulky adducts. This case-control study (250 breast
      cancer cases and 500 healthy controls) aimed to investigate the role of the XPD
      Lys751Gln polymorphism as a risk factor in the development of breast cancer.
      Genotyping was performed using the Taq Man allelic discrimination assay.
      Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic
      hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer
      patients. Results showed that the XPD Gln/Gln genotype was significantly
      associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80),
      particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH
      adduct levels were significantly higher in the cases with breast cancer as
      compared to the normal breast tissue. This study reveals that XPD may play a role
      in increasing breast cancer risk particularly in premenopausal females.

PMID- 22870146
TI  - Ductal adenocarcinoma of the pancreas: Expression of growth factor receptors,
      oncogenes and suppressor genes, and their relationship to pathological features,
      staging and survival.
AB  - Pancreatic ductal adenocarcinoma results in high short-term mortality despite
      recent advances in diagnostics, surgery and chemotherapy. Modern chemotherapeutic
      agents directed to specific tumor receptors have higher therapeutic efficacy and
      lower adverse effects. However, few studies exist that evaluate the clinical
      impact in pancreatic cancer. The expression of tumor growth factor receptors,
      oncogenes and tumor suppressor oncogenes in surgical pancreatic cancer specimens
      as related to pathological characteristics, staging and prognosis was evaluated.
      Data were recorded for 50 patients who underwent a pancreatic cancer resection
      and were suitable for immunohistochemical evaluation (32 male, mean age 61 years,
      range 44-78) with regard to pTN, tumor size and location, histological
      differentiation grade, vascular and perineural invasion, adjuvant chemotherapy
      and survival time. Tumor specimens and normal pancreatic tissue were
      deparaffinized and the expression of vascular epidermal growth factor (VEGF)
      receptors (R)-1 and -2, epidermal growth factor receptor (EGFR), Her-2/neu, COX
      2, p16, p21 and p53 was immunohistochemically evaluated using tissue microarrays.
      Associations between molecular marker expression and clinicopathological tumor
      characteristics were evaluated using the Chi-square test (SPSS) and the survival
      time was defined. The Kaplan-Meier method was utilized to analyze survival
      curves, verified by the log-rank test. No molecular markers evaluated were
      expressed in normal tissue. Tumor expression data included VEGF-R1 (74%), EGFR
      (52%), Her-2/neu (7.84%), COX-2 (21.5%), p16 (29.4%), p21 (21.7%) and p53 (50%).
      Tumors expressing VEGF-R1, EGFR and/or p53 were larger (p<0.02), frequently
      poorly differentiated (p<0.05) and more frequently associated with perineural and
      lymph node invasion (p<0.05). Marker expression did not correlate with
      pathological tumor characteristics. The median post-surgery survival was 15
      months; 60 and 27% patients survived to 12 and 24 months, respectively, with a
      longer survival time in patients receiving adjuvant chemotherapy (n=20) (median
      36 vs. 15 months, p<0.02). Growth factor receptors, oncogenes and tumor
      suppressor genes were frequently expressed in pancreatic cancer tissue. VEGF-R1,
      EGFR and p53 expression were associated with poor tissue differentiation and
      perineural and lymph node infiltration. Only VEGF-R1 expression was associated
      with a longer survival time and a more favorable response to adjuvant
      chemotherapy.

PMID- 22870147
TI  - Phase I study of docetaxel plus S-1 combination chemotherapy for recurrent non
      small cell lung cancer.
AB  - S-1 is a novel oral fluorouracil prodrug that plays a role in non-small cell lung
      cancer (NSCLC). Docetaxel (DTX) is one of the standard agents for relapsed NSCLC.
      We performed a phase I study of DTX plus S-1 combination therapy as second-line
      treatment for NSCLC to determine the maximum tolerated dose (MTD) and recommended
      dose (RD). Patients with recurrent NSCLC, aged 20-74 years with an Eastern
      Cooperative Oncology Group performance status of 0-1 and measurable lesions, were
      enrolled. The treatment consisted of four dose levels. The patients received DTX
      (40-60 mg/m(2) intravenously on day 1) and S-1 (65-80 mg/m(2) orally, daily on
      days 1-14) for each 21-day cycle. Three to six patients were treated at each dose
      level with the two drugs, with MTD defined as the dose level at which dose
      limiting toxicity (DLT) occurred in 33% of the patients. A total of 17 patients
      were enrolled. At dose level 4 (DTX, 60 mg/m(2); S-1, 80 mg/m(2)) 3 of 5 patients
      experienced DLT and this level was regarded as the MTD. Therefore, dose level 3
      (DTX, 60 mg/m(2); S-1, 65 mg/m(2)) was selected as the RD for subsequent studies.
      The DLTs were neutropenia (grade 4) and mucositis (grade 3). The response rate
      was 5.9% (1 of 17 patients achieved a partial response) and 14 of 17 patients
      achieved stable disease. This combination regimen showed a tolerable and
      manageable profile in recurrent NSCLC and therefore warrants further evaluation.

PMID- 22870148
TI  - Paraneoplastic encephalomyelitis: Is it an oropharyngeal or a lung cancer
      complication?
AB  - This case report describes a patient with a locally advanced oropharyngeal cancer
      with a simultaneous paraneoplastic encephalomyelitis. To the best of our
      knowledge, a paraneoplastic neurological syndrome is a rare complication in head
      and neck cancer, and has previously not been reported in the literature. One year
      later, following initial treatment, a small cell lung cancer developed, a tumor
      frequently associated with this type of paraneoplastic syndrome. The dilemma,
      therefore, is whether this paraneoplastic symdrome was a secondary complication
      of the tonsilar concurrent cancer or a metachronous paraneoplastic syndrome prior
      to small cell lung cancer.

PMID- 22870149
TI  - MicroRNA-124a and microRNA-34b/c are frequently methylated in all histological
      types of colorectal cancer and polyps, and in the adjacent normal mucosa.
AB  - MicroRNAs (miRs) are a class of small RNAs that regulate gene expression at the
      post-transcriptional and/or translational level by interacting with their target
      mRNAs. miRs are down-regulated or up-regulated in various cancer types,
      triggering abnormal cell differentiation, proliferation and apoptosis. miR-124a
      and miR-34b/c have been reported to be expressed at lower levels in colorectal
      cancer (CRC) due to methylation of these genes. The present study aimed to
      determine the methylation status of miR-124a and miR-34b/c in CRCs and polyps of
      various histological types, adjacent normal mucosa and ulcerative colitis. The
      colon cancer cell line study showed an association of the lower expression of miR
      124a and miR-34b/c with the methylation of these genes and induction of the
      expression of these genes with the treatment by 5-aza-2'-deoxycytidine. Among
      nine different cancer types examined, CRC showed the highest frequency of
      methylation of miR-124a (cell lines 88% and tissues 99%) and miR-34b/c (cell
      lines 89% and tissues 93%). Mucinous and non-mucinous CRCs and all the
      histological types of colorectal polyps showed a high frequency of methylation of
      miR-124a and miR-34b/c. Notably, methylation of miR-124a (59%) and miR-34b/c
      (26%) was observed in the adjacent normal mucosa of CRC patients, but not in
      colonic mucosa from patients without cancer or with ulcerative colitis. The
      methylation of miR-124a in the adjacent normal mucosa was associated with the
      microsatellite instability of CRC, while the methylation of miR-34b/c was
      associated with an older age at diagnosis of CRC. The results showed that the
      methylation of miR-124a and miR-34b/c occured early in colorectal carcinogenesis
      and certain CRCs may arise from a field defect defined by the epigenetic
      inactivation of miRs.

PMID- 22870150
TI  - Increased BCR promoter DNA methylation status strongly correlates with favorable
      response to imatinib in chronic myeloid leukemia patients.
AB  - To define the correlation between BCR promoter DNA methylation and response to
      imatinib in chronic myeloid leukemia (CML), we investigated BCR promoter DNA
      methylation in three groups of subjects. The first group included chronic phase
      patients enrolled in an imatinib dose escalation trial. In the trial, patients
      who failed to achieve optimal response with 400 mg/day (suboptimal responders)
      received an escalated imatinib dose. The level of BCR promoter DNA methylation
      was quantitated at baseline six months after dose escalation. The second group
      included patients who achieved complete cytogenetic remission after receiving 400
      mg/day of imatinib (optimal responders), and the third group were the healthy
      controls. In the suboptimal responders, an increased BCR promoter DNA methylation
      at six months compared with the baseline was related to a rapid reduction in the
      BCR-ABL/ABL transcript level following dose escalation (p=0.001) and a longer
      time to treatment failure (TTFx) of the dose-escalated imatinib (p=0.008). When
      multivariate analysis was performed with regard to the baseline BCR-ABL
      transcript level, baseline BCR promoter DNA methylation, and a change in the BCR
      promoter DNA methylation following dose escalation, the increase in the BCR
      promoter DNA methylation following dose escalation was an independent predictive
      factor for TTFx of dose-escalated imatinib (hazard ratio, 0.294; p=0.015). The
      baseline BCR promoter DNA methylation level in the suboptimal responders was
      lower than that in BCR promoter DNA methylation in the optimal responders
      (p=0.001) and healthy controls (p<0.001). In both the optimal and suboptimal
      responders, BCR promoter DNA methylation had an inverse correlation with the
      duration of the 400 mg/day imatinib use. In conclusion, increased BCR promoter
      DNA methylation strongly correlates with a more favorable imatinib response in
      CML patients.

PMID- 22870151
TI  - The challenges of the winds of change.

PMID- 22870152
TI  - Split cord malformations: A two years experience at AIIMS.
AB  - BACKGROUND: Over a 2-year period, 2008-2009, a total of 53 cases of split cord
      malformation (SCM) were treated at the All India Institute of Medical Sciences
      (AIIMS). This study is a retrospective analysis of clinical features,
      radiological findings, and surgical outcome of these patients. MATERIALS AND
      METHODS: During this period, 53 cases of SCM were treated at AIIMS. They
      constitute around 27% of all spinal dysraphism surgeries performed at the
      department of Neurosurgery, AIIMS; as 200 cases of spinal dysraphism were
      operated during the study period. The data was obtained from case files,
      operation notes, discharge summaries, and follow-up files. OBSERVATIONS: There
      were 30 cases of SCM type I and 23 cases of type II SCM. Seven patients were
      adult above 18 years of age. Except 7 patients, remaining 46 were symptomatic.
      Bony deformity of spine was recorded in 24 patients; of them, 19 had scoliosis
      and 4 had kyphosis. Deformity of foot was recorded in 10 patients. Thirteen
      patients had hypertrichosis, while four had dermal sinus. Magnetic resonance
      imaging (MRI) was performed in all patients. MRI revealed syringomyelia in 14
      patients; however, only one patient had associated Chiari malformation. Six
      patients had meningomyelocele. Intra-operative; thick filum was noticed in 10
      cases and in another 9 cases, there was filum lipoma. Dermoid was encountered in
      4 patients, one patient had epidermoid tumor. Site of split was thoracic in 22,
      followed by lumbar region in 21 patients. Only 3 patients had split in cervical
      spinal cord. Seven patients had two separate splits at two different levels. Two
      patients had posteriorly located bony spur. All patients underwent surgery. Seven
      patients, those who had no neurological deficits pre-op, remained unchanged post
      op. Amongst the 46 patients who had preoperative neurological deficits, eight had
      neurological deterioration post-op; five had deterioration in motor power and
      three had urinary problem. Five of these patients had type Id split, 2 had type
      Ic split, and one had type Ib split. However, among 8 patients who deteriorated
      post-op, four improved to preoperative status by the time of discharge. Thus,
      4/53(7%) patients had long-term deficits, all with type Id split. Follow-up data
      was available for 36 patients (68%) and mean follow-up period was 12 months
      (range 6-24 months). Follow-up MRI revealed decrease in syringomyelic cavity in 6
      of the 14 patients (44%) who had syringomyelia on preoperative MRI scans.
      CONCLUSION: Overall, SCM is an uncommon condition. In all cases of progressive
      scoliosis, MRI must be carried out. We subjected all asymptomatic patients to
      surgery and none developed post-op deterioration. Overall post-op neurological
      deterioration was noticed in 15% patients, of which 8% had transient post
      operative deterioration. The new Type I SCM subclassification system proposed by
      Mahapatra and Gupta is found to have a significant prognostic value in assessing
      post-operative neurological deterioration in patients with type I SCM.

PMID- 22870153
TI  - The study of systemic general circulation disturbance during the initiation of
      therapeutic hypothermia: Pit fall of hypothermia.
AB  - AIMS: Neurointensive care has reduced the mortality and improved the outcome of
      patients for severe brain damage, over recent decades, and made it possible to
      perform this therapy in safety. However, we have to understand the complications
      of this therapy well. The purpose of our study was to determine the systemic
      circulation disturbance during the initiation of therapeutic hypothermia by using
      this continuous neurointensive monitoring system. MATERIALS AND METHODS: Ten
      severe brain damage patients treated with hypothermia were enrolled. All patients
      had Glasgow Coma Scale (GCS) less than or equal to 8, on admission. RESULTS: We
      verified that heart rate, cardiac output, and oxygen delivery index (DO2I)
      decreased with decreasing core temperature. We recognized that depressed cardiac
      index (CI) was attributed to bradycardia, dehydration, and increased systemic
      vascular resistance index (SVRI) upon initiation of hypothermia. CONCLUSION:
      Although the hypothermia has a therapeutic role in severe brain damage patients,
      we have to carry out this therapy while maintaining their cardiac output using
      multimodality monitoring devices during hypothermia period.

PMID- 22870154
TI  - Pneumocephalus after surgical evacuation of chronic subdural hematoma: Is it a
      serious complication?
AB  - BACKGROUND: Pneumocephalus is commonly encountered after surgical evacuation of
      chronic subdural hematoma (CSDH). This study was done to study the incidence,
      clinical presentation, and management of patients who developed pneumocephalus
      after surgical evacuation of CSDH. MATERIALS AND METHODS: This prospective study
      was carried out on consecutive 50 patients who had received surgical treatment
      for CSDH. All the patients included were followed-up postoperatively with regular
      clinical and computed tomography (CT) examinations immediately postoperatively,
      before discharge, and 2 months after surgery. Pneumocephalus was classified into
      simple and tension, based upon the clinical and radiological criteria. The
      neurologic grading system of Markwalder et al was used to evaluate the surgical
      results. RESULTS: The immediate postoperative CT scan showed pneumocephalus in 22
      patients (44%). Tension pneumocephalus was found in two patients who did not
      require any further surgery. There was statistically significant increase in the
      incidence of pneumocephalus (immediate and postoperative) in the patients aged
      over 60 years as well as those presenting with a midline shift more than 5 mm in
      their CT scan. With regard to the 22 cases of pneumocephalus, good postoperative
      results were found in 16 patients (73%), while bad results were found in 6
      patients (27%). No statistically significant difference in the outcome between
      patients who had pneumocephalus after surgery and those who had not. CONCLUSION:
      Pneumocephalus after surgical evacuation of CSDH is a common finding in the
      immediate CT scan as well as at time of discharge. Tension pneumocephalus may not
      require surgical intervention and simple aspiration of air using a syringe may be
      sufficient.

PMID- 22870155
TI  - Telemedicine in neurosurgical emergency: Indian perspective.
AB  - Telemedicine is rapidly developing telecommunication technology to provide
      medical information and services. The importance of telemedicine for
      neurosurgical emergencies was established with the fact that majority of the
      neurosurgical specialists are practicing in urban settings and in most of the
      rural areas, neurosurgical care is far off or non-existing. Countries with
      inadequate health care must incorporate telemedicine in their health care system.
      Telemedicine offers real benefits in a country as vast as India, where the
      majority of the population lives in remote areas with no access to even the most
      basic healthcare. Issues pertaining security, privacy, maintaining standards, and
      legal aspects are relevant. A recommended set of standards and guidelines for
      telemedicine needs to be set in place and constantly refined to promote the
      integrated growth of telemedicine in the country. The paper discusses various
      issues, shortcomings, and utility of telemedicine in India.

PMID- 22870156
TI  - Innovative approach for prevention and treatment of post subarachnoid hemorrhage
      vasospasm: A preliminary report.
AB  - More than one third of patients with subarachnoid hemorrhage (SAH) develop
      clinically significant vasospasm, as a leading morbidity and mortality factor for
      these patients. It is widely accepted that a) Degradation products of blood are
      the causative factors of vasospasm b) The amount of subarachnoid blood seen on
      admission CT is correlated to the risk of vasospasm c) Reducing the subarachnoid
      clot burden at the time of surgery reduces the risk of vasospasm. But there is no
      existing method to clear the blood from subarachnoid spaces satisfactorily. We
      have evaluated safety and feasibility of fluid exchange catheter system in SAH,
      to achieve this goal. We were successful in clearing cisternal blood in three
      patients with aneurysmal rupture with fluid exchange catheter system. Baseline CT
      scan of brain was performed immediately after the surgery and then at the end of
      irrigation. The amount of subarachnoid blood was evaluated. This innovative,
      fluid exchange catheter system infuses and aspirates micro volumes of drug
      solution in a cyclic mode, ensuring isobaric exchange of fluids. The result is
      good clearance of blood in subarachnoid spaces were seen in all the patients.
      Also, significant improvement in neurological deficits secondary to vasospasm was
      seen. We conclude that the fluid exchange catheter system is safe and adoptable
      in neurosurgical practice.

PMID- 22870157
TI  - Dermoid cyst: A rare intramedullary inclusion cyst.
AB  - Intramedullary dermoid cysts are rare tumors, especially those not associated
      with spinal dysraphism. Only six cases have been reported in the literature. Of
      these, only two cases have had magnetic resonance imaging studies. We report a
      case of an 18-year-old female patient, who presented with progressive weakness of
      both the lower limbs and wasting of both the upper limbs. Magnetic resonance
      imaging (MRI) showed an intramedullary lesion extending from C3 to D2 with
      peripheral enhancement on contrast. Decompression of the cystic contents with
      partial removal of cyst wall was done. Hair with oily cholesterol and keratin
      debris was encountered. Histopathology confirmed the diagnosis of dermoid cyst.
      This case adds to the previous reported cases of the rare and uncommon
      intramedullary space occupying lesions of the spinal cord.

PMID- 22870158
TI  - A torcular encephalocele with proatlas defect and os-terminale.
AB  - Encephalocele means if meninges and brain tissue protrude out of the cranium.
      There are different types of encephalocele. The occipital encephaloceles are the
      most common type. Craniocervical junction and upper cervical spine abnormalities
      can rarely be associated with occipital encephalocele. We discuss this case
      because there is rare association between torcular encephalocele and proatlas
      anomalies.

PMID- 22870159
TI  - Asystole during posterior fossa surgery: Report of two cases.
AB  - Asystole during posterior fossa neurosurgical procedures is not uncommon. Various
      causes have been implicated, especially when surgical manipulation is carried out
      in the vicinity of the brain stem. The trigemino-cardiac reflex has been
      attributed as one of the causes. Here, we report two cases who suffered asystole
      during the resection of posterior fossa tumors. The vago-glossopharyngeal reflex
      and the direct stimulation of the brainstem were hypothesized as the causes of
      asytole. These episodes resolved spontaneously following withdrawal of the
      surgical stimulus emphasizing the importance of anticipation and vigilance during
      critical moments of tumor dissection during posterior fossa surgery.

PMID- 22870160
TI  - Isolated intramedullary spinal cord cysticercosis.
AB  - We report a case of intradural, intramedullary, spinal cord neurocysticercosis at
      dorsal 10-11 (D10-11) level in a mentally retarded male. A 38-year-old, mentally
      retarded male presented with weakness and stiffness in both the lower limbs and
      waist since one year. Magnetic resonance imaging revealed a D10-D11 intradural
      space occupying lesion with cord compression. Intraoperatively, the tumor was
      grayish white, soft, cystic, and intramedullary with a well-defined plane with
      surrounding cord tissue. Gross examination revealed a cystic lesion of 1.5*1*0.8
      cm, with a whitish nodule of 0.3 cm in diameter. The cyst wall was thin, shiny,
      and translucent. Microscopic examination revealed cysticercous cyst. Spinal
      neurocysticercosis should be considered in differential diagnosis of spinal mass
      lesion in patients residing in endemic area such as India.

PMID- 22870161
TI  - Petrous bone epidermoid cyst caused by penetrating injury to the external ear:
      Case report and review of literature.
AB  - Epidermoid cysts are histologically benign, slow-growing congenital neoplasms of
      the central nervous system that may arise from retained ectodermal implants. The
      epidermoid lesions are generally caused during the 3(rd) to 5(th) week of
      gestation by an incomplete cleavage of the neural tissue from the cutaneous
      ectoderm, though it can also happen later in life due to introduction of skin
      elements by skin puncture, trauma or surgery. We present this unique case of a
      petromastoid epidermoid cyst associated with ipsilateral cerebellar abscesses,
      presenting 20 years after a penetrating trauma to the external auditory canal.
      Radical excision of both lesions and revision of the previous fistulous tract was
      performed. We present the diagnostic challenge and the operative treatment of
      this unique case, which to our knowledge is the first where an epidermoid cyst
      and an adjacent brain abscess occurred as a result of a single traumatic event.

PMID- 22870162
TI  - Cerebral astroblastoma: A case report and review of literature.
AB  - Astroblastomas are uncommon neuroepithelial tumors of uncertain origin. These
      occur predominantly in the cerebral hemisphere of young adults and children. They
      form only 0.45-2.8% of all neuroglial tumors. They can be easily misdiagnosed as
      they are rarely encountered in clinical practice and share common radiological
      and histopathologic appearance with other glial neoplasms. A 12-year-old female
      presented to us with progressive headache and diplopia. Her neurological
      examination showed right 6(th) nerve paresis with papilledema. Brain magnetic
      resonance imaging (MRI) revealed well-demarcated, peripherally enhancing solid
      cystic mass of 6 cm in right parietal lobe with mass effect. She underwent gross
      total resection of the lesion through right parietal craniotomy. The
      histopathologic diagnosis was suggestive of low-grade astroblastoma. The patient
      had no evidence of recurrence of tumor without adjuvant radiotherapy during the
      last 14 months of follow-up. Supratentorial astroblastomas are very rare tumors.
      Complete excision without radiotherapy is sufficient in low-grade variants.

PMID- 22870163
TI  - Cervical osteochondroma presenting with acute quadriplegia.
AB  - Osteochondromas of the vertebral column are rare tumors and constitute about 3-4%
      of all primary vertebral column tumors. We report a case of osteochondroma
      arising from C3 lamina presenting with acute quadriplegia following a trivial
      fall. Computed Tomography (CT) and Magnetic Resonance imaging (MRI) showed bony
      lesion arising from C3 laminar arch compressing the cord with underlying spinal
      cord contusion. Emergency C3 laminectomy and complete enbloc excision of the
      lesion was performed, following which patient showed gradual recovery in
      neurological status. This acute presentation in this rare, slow growing, tumor
      has never been reported in literature till date.

PMID- 22870164
TI  - Delayed Positivization of Cerebral Angiography in Reversible Cerebral
      Vasoconstriction Syndrome (RCVS) Presenting with Recurrent Subarachnoid
      Haemorrhage.
AB  - Benign angiopathy of the central nervous system is a clinical syndrome with
      evidence of reversible cerebral vasoconstriction (RCVS). Haemorrhagic stroke,
      either subarachnoid or intracerebral is an unusual presentation of RCVS. We
      describe a case of RCVS presenting with a subarachnoid haemorrhage (SAH), with
      rebleeding and onset of hydrocephalus during the first week, and, notably,
      delayed evidence of typical angiographic features after two negative prior exams.
      Normalization of the angiographic vasculitic-like lesions was documented at month
      +6. Repeated cerebral angiograms are mandatory to exclude this kind of disease,
      and the uncommon presentation of this case reinforces this concept.

PMID- 22870165
TI  - Total recovery from monoclonal gammopathy and autoimmune phenomena after
      parathyroidectomy.
AB  - Based on the observation of a patient with a causal relationship between
      hyperparathyroidism and development of both autoimmune disease and
      paraproteinemia, we hypothesize a novel cause of autoimmunity triggered in the
      context of hyperparathyroidism.

PMID- 22870166
TI  - Symptom-modifying effect of chondroitin sulfate in knee osteoarthritis: a meta
      analysis of randomized placebo-controlled trials performed with structum((r)).
AB  - OBJECTIVE: To perform a meta-analysis of randomized double-blind placebo
      controlled clinical trials to assess the efficacy of a specific chondroitin
      sulfate preparation (Structum(r), Laboratoires Pierre Fabre, Castres; France) as
      a symptom-modifying drug in osteoarthritis (OA) of the knee. METHODS: A Medline
      search was conducted up to October 2010 and two articles reporting two trials
      were identified; one additional trial was identified through contacting the
      producer of Structum(r). There was no evidence of heterogeneity across the trials
      and results were pooled using a fixed effects model. RESULTS: Pooled results
      demonstrated a modest, but significant effect of Structum(r) (1 g daily) over
      placebo on the reduction of pain during activity following a treatment period of
      3-6 months of 6 mm (95% confidence interval (CI) -9.50, -1.72, p=0.005) on the
      visual analog scale (VAS) and a reduction in the algo-functional Index (AFI) by a
      weighted mean difference of -0.73 (95% CI -1.28 to -0.18, p=0.01). In addition,
      the pooled analysis demonstrated a statistically significant increase in OMERACT
      OARSI responders in the Structum(r)-treated patients by 20% (RR of 1.20 (95% CI
      1.06 to 1.36, p=0.003)), compared to placebo. CONCLUSION: These results
      demonstrate that this chondroitin sulfate preparation (Structum(r)) is effective
      on symptoms in patients with OA of the knee compared to placebo, and may
      therefore have a role in the management of patients with knee osteoarthritis of
      Kellgren-Lawrence grades II and III.

PMID- 22870167
TI  - Changes in Event-Related Desynchronization and Synchronization during the
      Auditory Oddball Task in Schizophrenia Patients.
AB  - OBJECTIVE: We studied differences in the spatiotemporal dynamics of cortical
      oscillation across brain regions of patients with schizophrenia and normal
      subjects during the auditory oddball task using magnetoencephalography (MEG) and
      electroencephalography (EEG). METHODS: Ten right-handed male schizophrenia
      patients were studied. We used a newly developed adaptive spatial filtering
      algorithm optimized for robust source time-frequency reconstruction of MEG and
      EEG data, and obtained consecutive images in functional maps of event-related
      desynchronization (ERD) and synchronization (ERS) in theta, lower alpha (8-10
      Hz), upper alpha (10-13 Hz), and beta bands. RESULTS: Beta ERD power at 750-1000
      ms in patients was significantly increased in large right upper temporal and
      parietal regions and small upper portions of bilateral dorsal frontal and dorsal
      medial parietal regions. Theta ERS power in schizophrenic patients during the
      oddball task was significantly increased in the left temporal pole at 250-500 ms,
      and was significantly increased in dorsal, medial frontal, and anterior portions
      of the anterior cingulate cortex in both hemispheres, and the left portion of
      lateral temporal regions at 500-750 ms, compared to the control group (family
      wise error correction p<0.05). Lower alpha ERS power was significantly decreased
      in the right occipital region at 500-750 ms and in the right midline parietal and
      bilateral occipital regions at 750-1000 ms. Upper alpha ERS power was
      significantly decreased in right midline parietal and left occipital regions at
      750-1000 ms. CONCLUSIONS: ERD/ERS changes were noted in the left temporal pole
      and midline frontal and anterior cingulate cortex in theta ERS, occipital lobe in
      alpha ERS, and right temporal-frontal-parietal, midline frontal, and anterior
      cingulate cortex in beta ERD. These findings may reflect disturbances in
      interaction among active large neuronal groups and their communication with each
      other that may be related to abnormal cognitive and psychopathological function.
      SIGNIFICANCE: Study of ERD and ERS by time-frequency analyses using MEG is useful
      to clarify data processing dysfunction in schizophrenia.

PMID- 22870168
TI  - Extension of Quantifiable Modification of sLORETA for Induced Oscillatory Changes
      in Magnetoencephalography.
AB  - Quantifiable modification of standardized low-resolution brain electromagnetic
      tomography (sLORETA-qm), which is one of the non-adaptive beamformer spatial
      filtering techniques, has been applied to source localization and quantification
      of evoked field or oscillatory changes in magnetoencephalography (MEG). Here, we
      extended this technique to induced oscillatory brain activity changes, so-called
      event-related desynchronization or event-related synchronization. For localizing
      of significantly activated brain areas at the whole-brain level, permutation
      tests and multiple comparison corrections with false discovery rate were applied.
      Induced beta- and gamma-band oscillatory changes by right hand clenching task
      were demonstrated as an example of simple induced brain activity.

PMID- 22870169
TI  - Malnutrition in spinal cord injury: more than nutritional deficiency.
AB  - Denervation of the spinal cord below the level of injury leads to complications
      producing malnutrition. Nutritional status affects mortality and pathology of
      injured subjects and it has been reported that two thirds of individuals enrolled
      in rehabilitation units are malnourished. Therefore, the aim should be either to
      maintain an optimal nutritional status, or supplement these subjects in order to
      overcome deficiencies in nutrients or prevent obesity. This paper reviews methods
      of nutritional assessment and describes the physiopathological mechanisms of
      malnutrition based on the assumption that spinal cord injured subjects need to
      receive adequate nutrition to promote optimal recovery, placing nutrition as a
      first line treatment and not an afterthought in the rehabilitation of spinal cord
      injury.

PMID- 22870170
TI  - On the management of hyperglycaemia in critically ill patients undergoing
      surgery.
AB  - Hyperglycaemia is a major health risk and a negative determinant of surgical
      outcome. Despite its increasing prevalence, the limited treatments for
      restoration of normoglycaemia make its effective management a highly complex
      individualized clinical art. In this context, we review the mechanisms leading to
      hyperglycaemic damage as the basis for effective management of surgical
      complications of diabetic and non diabetic critically ill patients.

PMID- 22870171
TI  - Missed Opportunities for Universal HIV Screening in Primary Care Clinics.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) has reported
      that the number of new cases of HIV infection has been underreported annually by
      at least 40,000 cases. In 2006, the CDC recommended that voluntary HIV counseling
      and testing (VCT) was given to all patients aged 13 to 64 years in ambulatory
      care settings. The purpose of this qualitative study was to explore primary care
      providers' (PCP) perspectives on and experiences of facilitators and barriers to
      offering VCT as part of annual screening. METHODS: This was a descriptive,
      exploratory study where fifteen primary care providers were individually
      interviewed. Only community-based primary care providers were interviewed, and no
      obstetrician/gynecologists were enrolled, as VCT is standard of care in that
      specialty. RESULTS: Barriers included doubts about the CDC recommendation, time
      constraints, fear, and assumptions about age and marital status. Facilitators
      included normalizing HIV testing and the availability of resources and training.
      PCPs' role as an advocate and their professional style had the paradoxical
      potential of being both a barrier and a facilitator to VCT. Providers' ability to
      connect patients to community resources was linked to their persistence and
      experience. CONCLUSIONS: Findings suggest more effort is needed by PCPs to
      facilitate HIV counseling and testing more frequently to their ambulatory care
      patients.

PMID- 22870172
TI  - Effects of 6-month sitagliptin treatment on glucose and lipid metabolism, blood
      pressure, body weight and renal function in type 2 diabetic patients: a chart
      based analysis.
AB  - BACKGROUND: Sitagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors
      which prevent the inactivation of incretins, increasing the endogenous active
      incretin levels. Incretins stimulate insulin secretion from pancreatic beta-cells
      and inhibit glucagon secretion from pancreatic alpha-cells, which is favorable
      for the treatment of diabetes. Sitagliptin is released on December, 2009, in
      Japan. We retrospectively studied effects of 6-month-treatment with sitagliptin
      on glucose and lipid metabolism, blood pressure, body weight and renal function
      in patients with type 2 diabetes by a chart-based analysis. METHODS: We
      retrospectively studied 220 type 2 diabetic patients who have taken sitagliptin
      for 6 months by a chart-based analysis. Subjects studied include patients treated
      with sitagliptin monotherapy, sitagliptin add-on therapy, and switching from
      glinide to sitagliptin. We selected patients who have both data before and after
      6-month sitagliptin treatment and compared the data before the sitagliptin
      treatment with the data at 6 month after the sitagliptin treatment started. Body
      weight, blood pressure, plasma glucose, hemoglobin A1c (HbA1c), serum lipids, and
      estimated glomerular filtration rate in type 2 diabetic patients were measured
      almost at the same time points before and after 6-month-treatment with
      sitagliptin. RESULTS: Body weight was significantly reduced after 6-month
      sitagliptin treatment by 0.8 kg. HbA1c levels were also significantly decreased
      after the sitagliptin treatment by 0.6%. We found a significant and negative
      correlation between change in body weight and body mass index at baseline. We
      also observed a significant and negative correlation between change in HbA1c and
      HbA1c levels at baseline. The number of patients who showed the absence of
      urinary glucose was significantly increased after the sitagliptin treatment.

PMID- 22870173
TI  - Multisegment foot kinematics during walking in younger and older adults.
AB  - BACKGROUND: Currently, age-related changes in foot mechanics are poorly
      understood. A greater understanding of the natural changes in foot motion is
      needed to improve our understanding of pathological foot conditions. METHODS: The
      purpose of this study was to compare multisegment foot kinematic data during gait
      in younger and older individuals. Eleven (N = 11) adult male participants between
      the ages of 18 - 30 years (younger group; mean +/- SD: 24.6 +/- 3.0 years) and
      eleven (N = 11) adults aged 55 years or older (older group; mean +/- SD: 65.0 +/-
      4.2 years) were recruited for the study. The foot was modeled as a four-segment
      rigid body model. Three-dimensional kinematic and kinetic gait parameters were
      recorded using an 8-camera Vicon MCam motion capture system and two Kistler force
      plates. A MANOVA was used to test for significant differences in mean temporal
      spatial data, mean ranges of motion, and mean peak joint angle data between age
      groups. RESULTS: No significant differences (P > 0.05) were found between the two
      age groups for any of the gait parameters. The results of the present study
      suggest that individuals aged 65.0 +/- 4.2 years have foot mechanics that are
      comparable to younger walkers. CONCLUSIONS: As such, any deviations in motion at
      this age may be indicative of an underlying disease or disorder.

PMID- 22870174
TI  - Coronary artery bypass grafting: 30-day operative morbidity analysis in 1046
      patients.
AB  - BACKGROUND: To determine the rate and risk factors of three operative
      complications (renal failure, pneumonia, and sternal wound infection) within 30
      days after isolated coronary artery bypass surgery. METHODS: Medical records of
      1,046 consecutive patients between the years 2005 and 2009 were reviewed.
      Demographic data and peri-operative information were collected and analyzed.
      Univariate and multivariate analysis between different variables were performed.
      RESULTS: Of all patients 3.6% developed pneumonia, 5.9% developed acute renal
      failure and 8.5% developed sternal wound infection. Independent predictors of
      acute renal failure were age > 65 years (P = 0.030), pre-operative renal
      impairment (P < 0.005), peripheral vascular disease (P = 0.005), emergency
      surgery (P = 0.043), blood transfusion (P = 0.002) mechanical ventilation > 12
      hours (P < 0.005) and prolonged inotropic support (P = 0.035). Pneumonia
      independent predictors were female gender (P < 0.005), diabetes mellitus (P =
      0.024), peripheral vascular disease (P = 0.012), emergency surgery (P = 0.007),
      blood transfusion (P = 0.001), mechanical ventilation > 12 hours (P = 0.005) and
      prolonged inotropic support (P < 0.005). Sternal wound infection independent
      predictors were diabetes mellitus (P = 0.017), intra- and post-operative blood
      transfusion (P < 0.005), and prolonged inotropic support (P = 0.006). CONCLUSION:
      Age, female gender, history of diabetes mellitus, chronic obstructive pulmonary
      disease, peripheral vascular disease, renal impairment, emergency surgery, per
      operative blood transfusion, mechanical ventilation > 12 hours and prolonged
      inotropic support are associated with the 30-day complication after on-pump
      isolated coronary artery bypass grafting surgery.

PMID- 22870175
TI  - Efficacy of feed forward and feedback signaling for inflations and chest
      compression pressure during cardiopulmonary resuscitation in a newborn mannequin.
AB  - BACKGROUND: The objective of the study was to evaluate a device that supports
      professionals during neonatal cardiopulmonary resuscitation (CPR). The device
      features a box that generates an audio-prompted rate guidance (feed forward) for
      inflations and compressions, and a transparent foil that is placed over the chest
      with marks for inter nipple line and sternum with LED's incorporated in the foil
      indicating the exerted force (feedback). METHODS: Ten pairs (nurse/doctor)
      performed CPR on a newborn resuscitation mannequin. All pairs initially performed
      two sessions. Thereafter two sessions were performed in similar way, after
      randomization in 5 pairs that used the device and 5 pairs that performed CPR
      without the device (controls). A rhythm score was calculated based on the number
      of CPR cycles that were performed correctly. RESULTS: The rhythm score with the
      device improved from 85 +/- 14 to 99 +/- 2% (P < 0.05). In the control group no
      differences were observed. The recorded pressures with the device increased from
      3.1 +/- 1.6 to 4.9 +/- 0.8 arbitrary units (P < 0.05). The second performance of
      the teams showed significant better results for the group with the CPR device
      compared to the controls. CONCLUSION: Feed forward and feedback signaling leads
      to a more constant rhythm and chest compression pressure during CPR.

PMID- 22870176
TI  - The relationship of metabolic syndrome with disease activity and the functional
      status in patients with rheumatoid arthritis.
AB  - BACKGROUND: The aim of this study is to investigate the frequency of metabolic
      syndrome (MS) in patients with rheumatoid arthritis (RA) and to determine the
      relationship between the clinical and laboratory parameters of RA and the
      components of the metabolic syndrome (MS). METHODS: Fifty-four patients with RA
      and 52 healthy individuals were enrolled in this study. The diagnosis of
      rheumatoid arthritis was based on the American College of Rheumatology criteria
      and the diagnosis of the metabolic syndrome was made according to the criteria
      set out in the American Heart Association/National Heart, Lung, and Blood
      Institute (AHA/NHLBI). The functional status and disease activity were also
      recorded in patients with RA. RESULTS: MS was diagnosed in 42.6% of the patients
      with RA and in 9.6% of the healthy controls. The systolic and diastolic blood
      pressure values were observed to be significantly higher in the patients with RA
      in comparison to the controls. Also, the frequency of MS was higher in the
      inferior functional group in relation to the higher functional group. A positive
      correlation was observed between the DAS28 scores and hypertension in patients
      with RA. CONCLUSIONS: In this study, MS was more frequently detected in the
      patients with RA compared to the control group. Also, an inferior functional
      status in RA was also found to be associated with the presence of MS. Thus, the
      presence of MS in patients with RA may be associated with a higher cardiovascular
      risk.

PMID- 22870177
TI  - Spinal cord meningioma: a treatable cause of paraplegia.
AB  - Chondrocalcinosis associated with Gitelman syndrome (GS) presents in young adults
      with either no symptoms or joint pain, muscle weakness, muscle cramps,
      paresthesias, episodes of tetany, or hypokalemic paralysis. Spinal cord
      meningiomas present with gradual onset of lower extremities weakness, numbness,
      pain, or balance problem. We report a 76 year old gentleman who presented with
      gradually progressive leg weakness puzzling the treating physicians.

PMID- 22870178
TI  - Biventricular Pacemaker Implantation via the Femoral Vein.
AB  - We report the case of biventricular pacemaker implantation via the femoral vein,
      in a patient with impossibility of using standard superior vein approach and a
      contraindication to epicardial lead placement.

PMID- 22870179
TI  - Insulin analogue levemir and development of pancreatic adenocarcinoma: a case
      report and literature review.
AB  - There is an association between insulin analogues, glargine, lispro and aspart
      and the incidence of malignancies. A 76 year-old female patient with history of
      diabetes, hypertension and hyperlipidemia presented with flank pain after using
      insulin Levemir as part of her management. CT abdomen revealed pancreatic mass
      and endoscopic ultrasound- guided FNA aspiration biopsy showed pancreatic
      adenocarcinoma. It was not clear whether the insulin analogue initiated the tumor
      or helped the growth of pre-existing malignant foci. Then we concluded that case
      presented raises an indicator of possible association between using insulin
      analogue and initiation of malignancies, or stimulation of malignant foci.

PMID- 22870180
TI  - Metronidazole-induced neurotoxicity developed in liver cirrhosis.
AB  - A 68 year-old-male with hepatitis C-positive liver cirrhosis was admitted because
      of liver abscess. After metronidazole was initiated against the infection, mental
      disturbance appeared. Hepatic encephalopathy was suspected at first, however, the
      brain MRI showed hyperintense lesion of the bilateral basal dendric nuclei which
      indicated metronidazole-associated encephalopathy. The symptoms became well after
      cessation of the drug. Metronidazole is a widely used medicine against various
      infections. Recent case reports describe that this medicine can induce reversible
      encephalopathy. However, there have been few reports regarding metronidazole
      induced encephalopathy occurred in patients with cirrhosis. Here we report on a
      case of hepatic cirrhosis and abscess in which reversible metronidazole-induced
      encephalopathy developed.

PMID- 22870181
TI  - A multicriteria decision making approach for estimating the number of clusters in
      a data set.
AB  - Determining the number of clusters in a data set is an essential yet difficult
      step in cluster analysis. Since this task involves more than one criterion, it
      can be modeled as a multiple criteria decision making (MCDM) problem. This paper
      proposes a multiple criteria decision making (MCDM)-based approach to estimate
      the number of clusters for a given data set. In this approach, MCDM methods
      consider different numbers of clusters as alternatives and the outputs of any
      clustering algorithm on validity measures as criteria. The proposed method is
      examined by an experimental study using three MCDM methods, the well-known
      clustering algorithm--k-means, ten relative measures, and fifteen public-domain
      UCI machine learning data sets. The results show that MCDM methods work fairly
      well in estimating the number of clusters in the data and outperform the ten
      relative measures considered in the study.

PMID- 22870182
TI  - Role of plastid transglutaminase in LHCII polyamination and thylakoid electron
      and proton flow.
AB  - Transglutaminases function as biological glues in animal cells, plant cells and
      microbes. In energy producing organelles such as chloroplasts the presence of
      transglutaminases was recently confirmed. Furthermore, a plastidial
      transglutaminase has been cloned from maize and the first plants overexpressing
      tgz are available (Nicotiana tabacum TGZ OE). Our hypothesis is that the
      overexpression of plastidal transglutaminase will alter photosynthesis via
      increased polyamination of the antenna of photosystem II. We have used standard
      analytical tools to separate the antenna from photosystem II in wild type and
      modified plants, 6 specific antibodies against LHCbs to confirm their presence
      and sensitive HPLC method to quantify the polyamination level of these proteins.
      We report that bound spermidine and spermine were significantly increased (~80%)
      in overexpressors. Moreover, we used recent advances in in vivo probing to study
      simultaneously the proton and electron circuit of thylakoids. Under physiological
      conditions overexpressors show a 3-fold higher sensitivity of the antenna down
      regulation loop (qE) to the elicitor (luminal protons) which is estimated as the
      DeltapH component of thylakoidal proton motive force. In addition, photosystem
      (hyper-PSIIalpha) with an exceptionally high antenna (large absorption cross
      section), accumulate in transglutaminase over expressers doubling the rate
      constant of light energy utilization (Kalpha) and promoting thylakoid membrane
      stacking. Polyamination of antenna proteins is a previously unrecognized
      mechanism for the modulation of the size (antenna absorption cross section) and
      sensitivity of photosystem II to down regulation. Future research will reveal
      which peptides and which residues of the antenna are responsible for such
      effects.

PMID- 22870183
TI  - The fate of the missing spores--patterns of realized dispersal beyond the closest
      vicinity of a sporulating moss.
AB  - It is well-known that many species with small diaspores can disperse far during
      extended temporal scales (many years). However, studies on short temporal scales
      usually only cover short distances (in, e.g., bryophytes up to 15 m). By using a
      novel experimental design, studying the realized dispersal, we extend this range
      by almost two orders of magnitude. We recorded establishment of the fast-growing
      moss Discelium nudum on introduced suitable substrates, placed around a
      translocated, sporulating mother colony. Around 2,000 pots with acidic clay were
      placed at different distances between 5 m and 600 m, in four directions, on a
      raised bog, with increased pot numbers with distance. The experiment was set up
      in April-May and the realized dispersal (number of colonized pots) was recorded
      in September. Close to the mother colony (up to 10 m), the mean colonization
      rates (ratio of colonized pots) exceeded 50%. At distances between 10 and 50 m
      colonization dropped sharply, but beyond 50 m the mean colonization rates
      stabilized and hardly changed (1-3%). The estimated density of spores causing
      establishments at the further distances (2-6 spores/m2) was realistic when
      compared to the estimated spore output from the central colonies. Our study
      supports calculations from earlier studies, limited to short distances, that a
      majority of the spores disperse beyond the nearest vicinity of a source. The even
      colonization pattern at further distances raises interesting questions about
      under what conditions spores are transported and deposited. However, it is clear
      that regular establishment is likely at the km-scale for this and many other
      species with similar spore output and dispersal mechanism.

PMID- 22870184
TI  - The organelle genomes of Hassawi rice (Oryza sativa L.) and its hybrid in saudi
      arabia: genome variation, rearrangement, and origins.
AB  - Hassawi rice (Oryza sativa L.) is a landrace adapted to the climate of Saudi
      Arabia, characterized by its strong resistance to soil salinity and drought.
      Using high quality sequencing reads extracted from raw data of a whole genome
      sequencing project, we assembled both chloroplast (cp) and mitochondrial (mt)
      genomes of the wild-type Hassawi rice (Hassawi-1) and its dwarf hybrid (Hassawi
      2). We discovered 16 InDels (insertions and deletions) but no SNP (single
      nucleotide polymorphism) is present between the two Hassawi cp genomes. We
      identified 48 InDels and 26 SNPs in the two Hassawi mt genomes and a new type of
      sequence variation, termed reverse complementary variation (RCV) in the rice cp
      genomes. There are two and four RCVs identified in Hassawi-1 when compared to 93
      11 (indica) and Nipponbare (japonica), respectively. Microsatellite sequence
      analysis showed there are more SSRs in the genic regions of both cp and mt
      genomes in the Hassawi rice than in the other rice varieties. There are also
      large repeats in the Hassawi mt genomes, with the longest length of 96,168 bp and
      96,165 bp in Hassawi-1 and Hassawi-2, respectively. We believe that frequent DNA
      rearrangement in the Hassawi mt and cp genomes indicate ongoing dynamic processes
      to reach genetic stability under strong environmental pressures. Based on
      sequence variation analysis and the breeding history, we suggest that both
      Hassawi-1 and Hassawi-2 originated from the Indonesian variety Peta since genetic
      diversity between the two Hassawi cultivars is very low albeit an unknown
      historic origin of the wild-type Hassawi rice.

PMID- 22870185
TI  - Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in
      Chinese (CRC) study.
AB  - OBJECTIVE: The American Diabetes Association (ADA) recently published new
      clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a
      diagnostic test for diabetes. The present study was to investigate the
      association between HbA1c and cardiovascular risk, and compare the associations
      with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). RESEARCH
      DESIGN AND METHODS: The study samples are from a community-based health
      examination survey in central China. Carotid-to-femoral pulse wave velocity
      (cfPWV) and HbA1c were measured in 5,098 men and women. RESULTS: After adjustment
      for age, sex, and BMI, the levels of HbA1c were significantly associated with an
      increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The
      associations remained significant after further adjustment for blood pressure,
      heart rate, and lipids (P = 0.004), and the difference in cfPWV between the
      highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h
      OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed
      additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and
      blood pressure significantly modified the associations between HbA1c and cfPWV (P
      for interactions <0.0001 for age; and  = 0.019 for blood pressure). The
      associations were stronger in subjects who were older (>=60 y; P for trend =
      0.004) and had higher blood pressure (>=120 [systolic blood pressure]/80 mmHg
      [diastolic blood pressure]; P for trend = 0.028) than those who were younger and
      had lower blood pressure (P for trend >0.05). CONCLUSIONS: HbA1c was related to
      high cfPWV, independent of conventional cardiovascular risk factors. Senior age
      and high blood pressure might amplify the adverse effects of HbA1c on
      cardiovascular risk.

PMID- 22870186
TI  - PRRT2 mutations in paroxysmal kinesigenic dyskinesia with infantile convulsions
      in a Taiwanese cohort.
AB  - BACKGROUND: Mutations in the PRRT2 gene have recently been identified in patients
      with familial paroxysmal kinesigenic dyskinesia with infantile convulsions
      (PKD/IC) and patients with sporadic PKD/IC from several ethnic groups. To extend
      these recent genetic reports, we investigated the frequency and identities of
      PRRT2 mutations in a cohort of Taiwanese patients with PKD/IC. METHODOLOGY AND
      PRINCIPAL FINDINGS: We screened all 3 coding exons of PRRT2 for mutations in 28
      Taiwanese patients with PKD/IC. Among them, 13 had familial PKD/IC and 15 were
      apparently sporadic cases. In total, 7 disparate mutations were identified in 13
      patients, including 8 familial cases and 5 apparently sporadic cases. The
      mutations were not present in 500 healthy controls. Four mutations were novel.
      One patient had a missense mutation and all other patients carried PRRT2
      mutations putatively resulting in a protein truncation. Haplotype analysis
      revealed that 5 of the 7 patients with the PRRT2 p.R217Pfs*8 mutation shared the
      same haplotype linked to the mutation. CONCLUSIONS AND SIGNIFICANCE: PRRT2
      mutations account for 61.5% (8 out of 13) of familial PKD/IC and 33.3% (5 out of
      15) of apparently sporadic PKD/IC in the Taiwanese cohort. Most patients with the
      PRRT2 p.R217Pfs*8 mutation in Taiwan likely descend from a single common
      ancestor. This study expands the spectrum of PKD/IC-associated PRRT2 mutations,
      highlights the pathogenic role of PRRT2 mutations in PKD/IC, and suggests genetic
      heterogeneity within idiopathic PKD.

PMID- 22870187
TI  - Expression profile of genes during resistance reversal in a temephos selected
      strain of the dengue vector, Aedes aegypti.
AB  - BACKGROUND: The mosquito Aedes aegypti is one of the most important disease
      vectors because it transmits two major arboviruses, dengue and yellow fever,
      which cause significant global morbidity and mortality. Chemical insecticides
      form the cornerstone of vector control. The organophosphate temephos a larvicide
      recommended by WHO for controlling Ae. aegypti, however, resistance to this
      compound has been reported in many countries, including Brazil.
      METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to identify genes
      implicated in metabolic resistance in an Ae. aegypti temephos resistant strain,
      named RecR, through microarray analysis. We utilized a custom 'Ae. aegypti detox
      chip' and validated microarray data through RT-PCR comparing susceptible and
      resistant individuals. In addition, we analyzed gene expression in 4(th) instar
      larvae from a reversed susceptible strain (RecRev), exposed and unexposed to
      temephos. The results obtained revealed a set of 13 and 6 genes significantly
      over expressed in resistant adult mosquitoes and larvae, respectively. One of
      these genes, the cytochrome P450 CYP6N12, was up-regulated in both stages. RT-PCR
      confirmed the microarray results and, additionally, showed no difference in gene
      expression between temephos exposed and unexposed RecRev mosquitoes. This
      suggested that the differences in the transcript profiles among the strains are
      heritable due to a selection process and are not caused by immediate insecticide
      exposure. Reversal of temephos resistance was demonstrated and, importantly,
      there was a positive correlation between a decrease in the resistance ratio and
      an accompanying decrease in the expression levels of previously over expressed
      genes. Some of the genes identified here have also been implicated in metabolic
      resistance in other mosquito species and insecticide resistant populations of Ae.
      aegypti. CONCLUSIONS/SIGNIFICANCE: The identification of gene expression
      signatures associated to insecticide resistance and their suppression could
      greatly aid the development of improved strategies of vector control.

PMID- 22870188
TI  - Genetic knockdown of brain-derived neurotrophic factor in 3xTg-AD mice does not
      alter Abeta or tau pathology.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin critically involved in
      cell survival, synaptic plasticity, and memory. BDNF has recently garnered
      significant attention as a potential therapeutic target for neurodegenerative
      diseases such as Alzheimer disease (AD), but emerging evidence suggests that BDNF
      may also be mechanistically involved in the pathogenesis of AD. AD patients have
      substantially reduced BDNF levels, which may be a result of Abeta and tau
      pathology. Recent evidence, however, indicates reduced BDNF levels may also serve
      to drive pathology in neuronal cultures, although this has not yet been
      established in vivo. To further investigate the mechanistic role of BDNF in AD,
      we generated 3xTg-AD mice with a heterozygous BDNF knockout (BDNF(+/-)) and
      analyzed Abeta and tau pathology. Aged 3xTg-AD/BDNF(+/-) mice have significantly
      reduced levels of brain BDNF, but have comparable levels of Abeta and tau
      pathology to 3xTg-AD/BDNF(+/+) mice. These findings indicate that chronic
      reduction of BDNF does not exacerbate the development of Abeta and tau pathology,
      and instead suggests the reduced BDNF levels found in AD patients are a
      consequence of these pathologies.

PMID- 22870189
TI  - ChIPnorm: a statistical method for normalizing and identifying differential
      regions in histone modification ChIP-seq libraries.
AB  - The advent of high-throughput technologies such as ChIP-seq has made possible the
      study of histone modifications. A problem of particular interest is the
      identification of regions of the genome where different cell types from the same
      organism exhibit different patterns of histone enrichment. This problem turns out
      to be surprisingly difficult, even in simple pairwise comparisons, because of the
      significant level of noise in ChIP-seq data. In this paper we propose a two-stage
      statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find
      differential regions in the genome, given two libraries of histone modifications
      of different cell types. We show that the ChIPnorm method removes most of the
      noise and bias in the data and outperforms other normalization methods. We
      correlate the histone marks with gene expression data and confirm that histone
      modifications H3K27me3 and H3K4me3 act as respectively a repressor and an
      activator of genes. Compared to what was previously reported in the literature,
      we find that a substantially higher fraction of bivalent marks in ES cells for
      H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the
      promoter regions in protein-coding genes have differential histone-modification
      sites. The software for this work can be downloaded from
      http://lcbb.epfl.ch/software.html.

PMID- 22870190
TI  - A novel 5-enolpyruvylshikimate-3-phosphate synthase from Rahnella aquatilis with
      significantly reduced glyphosate sensitivity.
AB  - The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19) is a key
      enzyme in the shikimate pathway for the production of aromatic amino acids and
      chorismate-derived secondary metabolites in plants, fungi, and microorganisms. It
      is also the target of the broad-spectrum herbicide glyphosate. Natural glyphosate
      resistance is generally thought to occur within microorganisms in a strong
      selective pressure condition. Rahnella aquatilis strain GR20, an antagonist
      against pathogenic agrobacterial strains of grape crown gall, was isolated from
      the rhizosphere of grape in glyphosate-contaminated vineyards. A novel gene
      encoding EPSPS was identified from the isolated bacterium by complementation of
      an Escherichia coli auxotrophic aroA mutant. The EPSPS, named AroA(R. aquatilis),
      was expressed and purified from E. coli, and key kinetic values were determined.
      The full-length enzyme exhibited higher tolerance to glyphosate than the E. coli
      EPSPS (AroA(E. coli)), while retaining high affinity for the substrate
      phosphoenolpyruvate. Transgenic plants of AroA(R. aquatilis) were also observed
      to be more resistant to glyphosate at a concentration of 5 mM than that of
      AroA(E. coli). To probe the sites contributing to increased tolerance to
      glyphosate, mutant R. aquatilis EPSPS enzymes were produced with the c-strand of
      subdomain 3 and the f-strand of subdomain 5 (Thr38Lys, Arg40Val, Arg222Gln,
      Ser224Val, Ile225Val, and Gln226Lys) substituted by the corresponding region of
      the E. coli EPSPS. The mutant enzyme exhibited greater sensitivity to glyphosate
      than the wild type R. aquatilis EPSPS with little change of affinity for its
      first substrate, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). The
      effect of the residues on subdomain 5 on glyphosate resistance was more obvious.

PMID- 22870191
TI  - The role of corpus callosum development in functional connectivity and cognitive
      processing.
AB  - The corpus callosum is hypothesized to play a fundamental role in integrating
      information and mediating complex behaviors. Here, we demonstrate that lack of
      normal callosal development can lead to deficits in functional connectivity that
      are related to impairments in specific cognitive domains. We examined resting
      state functional connectivity in individuals with agenesis of the corpus callosum
      (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of
      coherence in the alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-55 Hz) bands.
      Global connectivity (GC) was defined as synchronization between a region and the
      rest of the brain. In AgCC individuals, alpha band GC was significantly reduced
      in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto
      occipital cortices (PO). No significant differences in GC were seen in either the
      beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional
      reduction in functional connectivity is explained primarily by a specific
      reduction in interhemispheric connectivity. However, our data suggest that
      reduced connectivity in these regions is driven by faulty coupling in both inter-
      and intrahemispheric connectivity. We also assessed whether the degree of
      connectivity correlated with behavioral performance, focusing on cognitive
      measures known to be impaired in AgCC individuals. Neuropsychological measures of
      verbal processing speed were significantly correlated with resting-state
      functional connectivity of the left medial and superior temporal lobe in AgCC
      participants. Connectivity of DLPFC correlated strongly with performance on the
      Tower of London in the AgCC cohort. These findings indicate that the abnormal
      callosal development produces salient but selective (alpha band only) resting
      state functional connectivity disruptions that correlate with cognitive
      impairment. Understanding the relationship between impoverished functional
      connectivity and cognition is a key step in identifying the neural mechanisms of
      language and executive dysfunction in common neurodevelopmental and psychiatric
      disorders where disruptions of callosal development are consistently identified.

PMID- 22870192
TI  - Association between tetrodotoxin resistant channels and lipid rafts regulates
      sensory neuron excitability.
AB  - Voltage-gated sodium channels (VGSCs) play a key role in the initiation and
      propagation of action potentials in neurons. Na(V)1.8 is a tetrodotoxin (TTX)
      resistant VGSC expressed in nociceptors, peripheral small-diameter neurons able
      to detect noxious stimuli. Na(V)1.8 underlies the vast majority of sodium
      currents during action potentials. Many studies have highlighted a key role for
      Na(V)1.8 in inflammatory and chronic pain models. Lipid rafts are microdomains of
      the plasma membrane highly enriched in cholesterol and sphingolipids. Lipid rafts
      tune the spatial and temporal organisation of proteins and lipids on the plasma
      membrane. They are thought to act as platforms on the membrane where proteins and
      lipids can be trafficked, compartmentalised and functionally clustered. In the
      present study we investigated Na(V)1.8 sub-cellular localisation and explored the
      idea that it is associated with lipid rafts in nociceptors. We found that
      Na(V)1.8 is distributed in clusters along the axons of DRG neurons in vitro and
      ex vivo. We also demonstrated, by biochemical and imaging studies, that Na(V)1.8
      is associated with lipid rafts along the sciatic nerve ex vivo and in DRG neurons
      in vitro. Moreover, treatments with methyl-beta-cyclodextrin (MbetaCD) and 7
      ketocholesterol (7KC) led to the dissociation between rafts and Na(V)1.8. By
      calcium imaging we demonstrated that the lack of association between rafts and
      Na(V)1.8 correlated with impaired neuronal excitability, highlighted by a
      reduction in the number of neurons able to conduct mechanically- and chemically
      evoked depolarisations. These findings reveal the sub-cellular localisation of
      Na(V)1.8 in nociceptors and highlight the importance of the association between
      Na(V)1.8 and lipid rafts in the control of nociceptor excitability.

PMID- 22870193
TI  - Regulation of gene expression with thyroid hormone in rats with myocardial
      infarction.
AB  - INTRODUCTION: The expression of hundreds of genes is altered in response to left
      ventricular (LV) remodeling following large transmural myocardial infarction
      (MI). Thyroid hormone (TH) improves LV remodeling and cardiac performance after
      MI. However, the molecular basis is unknown. METHODS: MI was produced by ligation
      of the left anterior descending coronary artery in female SD rats. Rats were
      divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment
      (T4 pellet 3.3 mg, 60 days release, implanted subcutaneously immediately
      following MI). Four weeks after surgery, total RNA was isolated from LV non
      infarcted areas for microarray analysis using the Illumina RatRef-12 Expression
      BeadChip Platform. RESULTS: Signals were detected in 13,188 genes (out of
      22,523), of which the expression of 154 genes were decreased and the expression
      of 200 genes were increased in MI rats compared with Sham MI rats (false
      discovery rate (FDR) <0.05). Compared to MI rats, T4 treatment decreased
      expression of 27 genes and increased expression of 28 genes. In particular, 6
      genes down-regulated by MI and 12 genes up-regulated by MI were reversed by T4.
      Most of the 55 genes altered by T4 treatment are in the category of molecular
      function under binding (24) and biological processes which includes immune system
      process (9), multi-organism process (5) and biological regulation (19)
      nonexclusively. CONCLUSIONS: These results suggest that altered expression of
      genes for molecular function and biological process may be involved in the
      beneficial effects of thyroid hormone treatment following MI in rats.

PMID- 22870194
TI  - Characterization of transposable elements in the ectomycorrhizal fungus Laccaria
      bicolor.
AB  - BACKGROUND: The publicly available Laccaria bicolor genome sequence has provided
      a considerable genomic resource allowing systematic identification of
      transposable elements (TEs) in this symbiotic ectomycorrhizal fungus. Using a TE
      specific annotation pipeline we have characterized and analyzed TEs in the L.
      bicolor S238N-H82 genome. METHODOLOGY/PRINCIPAL FINDINGS: TEs occupy 24% of the
      60 Mb L. bicolor genome and represent 25,787 full-length and partial copy
      elements distributed within 171 families. The most abundant elements were the
      Copia-like. TEs are not randomly distributed across the genome, but are tightly
      nested or clustered. The majority of TEs exhibits signs of ancient transposition
      except some intact copies of terminal inverted repeats (TIRS), long terminal
      repeats (LTRs) and a large retrotransposon derivative (LARD) element. There were
      three main periods of TE expansion in L. bicolor: the first from 57 to 10 Mya,
      the second from 5 to 1 Mya and the most recent from 0.5 Mya ago until now. LTR
      retrotransposons are closely related to retrotransposons found in another
      basidiomycete, Coprinopsis cinerea. CONCLUSIONS: This analysis 1) represents an
      initial characterization of TEs in the L. bicolor genome, 2) contributes to
      improve genome annotation and a greater understanding of the role TEs played in
      genome organization and evolution and 3) provides a valuable resource for future
      research on the genome evolution within the Laccaria genus.

PMID- 22870196
TI  - The eyes have it: sex and sexual orientation differences in pupil dilation
      patterns.
AB  - Recent research suggests profound sex and sexual orientation differences in
      sexual response. These results, however, are based on measures of genital
      arousal, which have potential limitations such as volunteer bias and differential
      measures for the sexes. The present study introduces a measure less affected by
      these limitations. We assessed the pupil dilation of 325 men and women of various
      sexual orientations to male and female erotic stimuli. Results supported
      hypotheses. In general, self-reported sexual orientation corresponded with pupil
      dilation to men and women. Among men, substantial dilation to both sexes was most
      common in bisexual-identified men. In contrast, among women, substantial dilation
      to both sexes was most common in heterosexual-identified women. Possible reasons
      for these differences are discussed. Because the measure of pupil dilation is
      less invasive than previous measures of sexual response, it allows for studying
      diverse age and cultural populations, usually not included in sexuality research.

PMID- 22870195
TI  - Laropiprant attenuates EP3 and TP prostanoid receptor-mediated thrombus
      formation.
AB  - The use of the lipid lowering agent niacin is hampered by a frequent flush
      response which is largely mediated by prostaglandin (PG) D(2). Therefore,
      concomitant administration of the D-type prostanoid (DP) receptor antagonist
      laropiprant has been proposed to be a useful approach in preventing niacin
      induced flush. However, antagonizing PGD(2), which is a potent inhibitor of
      platelet aggregation, might pose the risk of atherothrombotic events in
      cardiovascular disease. In fact, we found that in vitro treatment of platelets
      with laropiprant prevented the inhibitory effects of PGD(2) on platelet function,
      i.e. platelet aggregation, Ca(2+) flux, P-selectin expression, activation of
      glycoprotein IIb/IIIa and thrombus formation. In contrast, laropiprant did not
      prevent the inhibitory effects of acetylsalicylic acid or niacin on thrombus
      formation. At higher concentrations, laropiprant by itself attenuated platelet
      activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor
      stimulation, as demonstrated in assays of platelet aggregation, Ca(2+) flux, P
      selectin expression, and activation of glycoprotein IIb/IIIa. Inhibition of
      platelet function exerted by EP4 or I-type prostanoid (IP) receptors was not
      affected by laropiprant. These in vitro data suggest that niacin/laropiprant for
      the treatment of dyslipidemias might have a beneficial profile with respect to
      platelet function and thrombotic events in vascular disease.

PMID- 22870197
TI  - In vitro model of metastasis to bone marrow mediates prostate cancer castration
      resistant growth through paracrine and extracellular matrix factors.
AB  - The spread of prostate cancer cells to the bone marrow microenvironment and
      castration resistant growth are key steps in disease progression and significant
      sources of morbidity. However, the biological significance of mesenchymal stem
      cells (MSCs) and bone marrow derived extracellular matrix (BM-ECM) in this
      process is not fully understood. We therefore established an in vitro engineered
      bone marrow tissue model that incorporates hMSCs and BM-ECM to facilitate
      mechanistic studies of prostate cancer cell survival in androgen-depleted media
      in response to paracrine factors and BM-ECM. hMSC-derived paracrine factors
      increased LNCaP cell survival, which was in part attributed to IGFR and IL6
      signaling. In addition, BM-ECM increased LNCaP and MDA-PCa-2b cell survival in
      androgen-depleted conditions, and induced chemoresistance and morphological
      changes in LNCaPs. To determine the effect of BM-ECM on cell signaling, the
      phosphorylation status of 46 kinases was examined. Increases in the
      phosphorylation of MAPK pathway-related proteins as well as sustained Akt
      phosphorylation were observed in BM-ECM cultures when compared to cultures grown
      on plasma-treated polystyrene. Blocking MEK1/2 or the PI3K pathway led to a
      significant reduction in LNCaP survival when cultured on BM-ECM in androgen
      depleted conditions. The clinical relevance of these observations was determined
      by analyzing Erk phosphorylation in human bone metastatic prostate cancer versus
      non-metastatic prostate cancer, and increased phosphorylation was seen in the
      metastatic samples. Here we describe an engineered bone marrow model that mimics
      many features observed in patients and provides a platform for mechanistic in
      vitro studies.

PMID- 22870199
TI  - The relationship between genus richness and geographic area in Late Cretaceous
      marine biotas: epicontinental sea versus open-ocean-facing settings.
AB  - For present-day biotas, close relationships have been documented between the
      number of species in a given region and the area of the region. To date, however,
      there have been only limited studies of these relationships in the geologic
      record, particularly for ancient marine biotas. The recent development of large
      scale marine paleontological databases, in conjunction with enhanced geographical
      mapping tools, now allow for their investigation. At the same time, there has
      been renewed interest in comparing the environmental and paleobiological
      properties of two broad-scale marine settings: epicontinental seas, broad
      expanses of shallow water covering continental areas, and open-ocean-facing
      settings, shallow shelves and coastlines that rim ocean basins. Recent studies
      indicate that spatial distributions of taxa and the kinetics of taxon origination
      and extinction may have differed in these two settings. Against this backdrop, we
      analyze regional Genus-Area Relationships (GARs) of Late Cretaceous marine
      invertebrates in epicontinental sea and open-ocean settings using data from the
      Paleobiology Database. We present a new method for assessing GARs that is
      particularly appropriate for fossil data when the geographic distribution of
      these data is patchy and uneven. Results demonstrate clear relationships between
      genus richness and area for regions worldwide, but indicate that as area
      increases, genus richness increases more per unit area in epicontinental seas
      than in open-ocean settings. This difference implies a greater degree of
      compositional heterogeneity as a function of geographic area in epicontinental
      sea settings, a finding that is consistent with the emerging understanding of
      physical differences in the nature of water masses between the two marine
      settings.

PMID- 22870198
TI  - Avian resistance to Campylobacter jejuni colonization is associated with an
      intestinal immunogene expression signature identified by mRNA sequencing.
AB  - Campylobacter jejuni is the most common cause of human bacterial gastroenteritis
      and is associated with several post-infectious manifestations, including onset of
      the autoimmune neuropathy Guillain-Barre syndrome, causing significant morbidity
      and mortality. Poorly-cooked chicken meat is the most frequent source of
      infection as C. jejuni colonizes the avian intestine in a commensal relationship.
      However, not all chickens are equally colonized and resistance seems to be
      genetically determined. We hypothesize that differences in immune response may
      contribute to variation in colonization levels between susceptible and resistant
      birds. Using high-throughput sequencing in an avian infection model, we
      investigate gene expression associated with resistance or susceptibility to
      colonization of the gastrointestinal tract with C. jejuni and find that gut
      related immune mechanisms are critical for regulating colonization. Amongst a
      single population of 300 4-week old chickens, there was clear segregation in
      levels of C. jejuni colonization 48 hours post-exposure. RNAseq analysis of
      caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds
      generated over 363 million short mRNA sequences which were investigated to
      identify 219 differentially expressed genes. Significantly higher expression of
      genes involved in the innate immune response, cytokine signaling, B cell and T
      cell activation and immunoglobulin production, as well as the renin-angiotensin
      system was observed in resistant birds, suggesting an early active immune
      response to C. jejuni. Lower expression of these genes in colonized birds
      suggests suppression or inhibition of a clearing immune response thus
      facilitating commensal colonization and generating vectors for zoonotic
      transmission. This study describes biological processes regulating C. jejuni
      colonization of the avian intestine and gives insight into the differential
      immune mechanisms incited in response to commensal bacteria in general within
      vertebrate populations. The results reported here illustrate how an exaggerated
      immune response may be elicited in a subset of the population, which alters host
      microbe interactions and inhibits the commensal state, therefore having wider
      relevance with regard to inflammatory and autoimmune disease.

PMID- 22870200
TI  - Technology acceptance for an Intelligent Comprehensive Interactive Care (ICIC)
      system for care of the elderly: a survey-questionnaire study.
AB  - The key components of caring for the elderly are diet, living, transportation,
      education, and safety issues, and telemedical systems can offer great assistance.
      Through the integration of personal to community information technology
      platforms, we have developed a new Intelligent Comprehensive Interactive Care
      (ICIC) system to provide comprehensive services for elderly care. The ICIC system
      consists of six items, including medical care (physiological measuring system,
      Medication Reminder, and Dr. Ubiquitous), diet, living, transportation, education
      (Intelligent Watch), entertainment (Sharetouch), and safety (Fall Detection). In
      this study, we specifically evaluated the users' intention of using the
      Medication Reminder, Dr. Ubiquitous, Sharetouch, and Intelligent Watch using a
      modified technological acceptance model (TAM). A total of 121 elderly subjects
      (48 males and 73 females) were recruited. The modified TAM questionnaires were
      collected after they had used these products. For most of the ICIC units, the
      elderly subjects revealed great willingness and/or satisfaction in using this
      system. The elderly users of the Intelligent Watch showed the greatest
      willingness and satisfaction, while the elderly users of Dr. Ubiquitous revealed
      fair willingness in the dimension of perceived ease of use. The old-old age group
      revealed greater satisfaction in the dimension of result demonstrability for the
      users of the Medication Reminder as compared to the young-old and oldest-old age
      groups. The women revealed greater satisfaction in the dimension of perceived
      ease of use for the users of Dr. Ubiquitous as compared to the men. There were no
      statistically significant differences in terms of gender, age, and education
      level in the other dimensions. The modified TAM showed its effectiveness in
      evaluating the acceptance and characteristics of technologic products for the
      elderly user. The ICIC system offers a user-friendly solution in telemedical care
      and improves the quality of care for the elderly.

PMID- 22870201
TI  - Vitamin D4 in mushrooms.
AB  - An unknown vitamin D compound was observed in the HPLC-UV chromatogram of edible
      mushrooms in the course of analyzing vitamin D(2) as part of a food composition
      study and confirmed by liquid chromatography-mass spectrometry to be vitamin D(4)
      (22-dihydroergocalciferol). Vitamin D(4) was quantified by HPLC with UV
      detection, with vitamin [(3)H] itamin D(3) as an internal standard. White button,
      crimini, portabella, enoki, shiitake, maitake, oyster, morel, chanterelle, and UV
      treated portabella mushrooms were analyzed, as four composites each of a total of
      71 samples from U.S. retail suppliers and producers. Vitamin D(4) was present
      (>0.1 ug/100 g) in a total of 18 composites and in at least one composite of each
      mushroom type except white button. The level was highest in samples with known UV
      exposure: vitamin D enhanced portabella, and maitake mushrooms from one supplier
      (0.2-7.0 and 22.5-35.4 ug/100 g, respectively). Other mushrooms had detectable
      vitamin D(4) in some but not all samples. In one composite of oyster mushrooms
      the vitamin D(4) content was more than twice that of D(2) (6.29 vs. 2.59 ug/100
      g). Vitamin D(4) exceeded 2 ug/100 g in the morel and chanterelle mushroom
      samples that contained D(4), but was undetectable in two morel samples. The
      vitamin D(4) precursor 22,23-dihydroergosterol was found in all composites (4.49
      16.5 mg/100 g). Vitamin D(4) should be expected to occur in mushrooms exposed to
      UV light, such as commercially produced vitamin D enhanced products, wild grown
      mushrooms or other mushrooms receiving incidental exposure. Because vitamin D(4)
      coeluted with D(3) in the routine HPLC analysis of vitamin D(2) and an alternate
      mobile phase was necessary for resolution, researchers analyzing vitamin D(2) in
      mushrooms and using D(3) as an internal standard should verify that the system
      will resolve vitamins D(3) and D(4).

PMID- 22870202
TI  - In vitro and in vivo prostate cancer metastasis and chemoresistance can be
      modulated by expression of either CD44 or CD147.
AB  - CD44 and CD147 are associated with cancer metastasis and progression. Our purpose
      in the study was to investigate the effects of down-regulation of CD44 or CD147
      on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX)
      responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and
      CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA
      (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and
      MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and
      Western blotting. The DTX dose-response and proliferation was measured by MTT and
      colony assays, respectively. The invasive potential was assessed using a matrigel
      chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways
      were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model
      was established to assess CaP tumorigenecity, lymph node metastases and DTX
      response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2
      expression, reduced CaP proliferation and invasive potential and enhanced DTX
      sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main
      signal modulators associated with cell growth and survival. In vivo, CD44 or
      CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased
      DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance
      metastatic capacity and chemoresistance of CaP cells, potentially mediated by
      activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone
      or combined with DTX may limit CaP metastasis and increase chemosensitivity, with
      promise for future CaP treatment.

PMID- 22870203
TI  - Solvent free fabrication of micro and nanostructured drug coatings by thermal
      evaporation for controlled release and increased effects.
AB  - Nanostructuring of drug delivery systems offers many promising applications like
      precise control of dissolution and release kinetics, enhanced activities,
      flexibility in terms of surface coatings, integration into implants, designing
      the appropriate scaffolds or even integrating into microelectronic chips etc. for
      different desired applications. In general such kind of structuring is difficult
      due to unintentional mixing of chemical solvents used during drug formulations.
      We demonstrate here the successful solvent-free fabrication of micro
      nanostructured pharmaceutical molecules by simple thermal evaporation (TE). The
      evaporation of drug molecules and their emission to a specific surface under
      vacuum led to controlled assembling of the molecules from vapour phase to solid
      phase. The most important aspects of thermal evaporation technique are: solvent
      free, precise control of size, possibility of fabricating multilayer/hybrid, and
      free choice of substrates. This could be shown for twenty eight pharmaceutical
      substances of different chemical structures which were evaporated on surfaces of
      titanium and glass discs. Structural investigations of different TE fabricated
      drugs were performed by atomic force microscopy, scanning electron microscopy and
      Raman spectroscopy which revealed that these drug substances preserve their
      structurality after evaporation. Titanium discs coated with antimicrobial
      substances by thermal evaporation were subjected to tests for antibacterial or
      antifungal activities, respectively. A significant increase in their
      antimicrobial activity was observed in zones of inhibition tests compared to
      controls of the diluted substances on the discs made of paper for filtration.
      With thermal evaporation, we have successfully synthesized solvent-free
      nanostructured drug delivery systems in form of multilayer structures and in
      hybrid drug complexes respectively. Analyses of these substances consolidated
      that thermal evaporation opens up the possibility to convert dissoluble drug
      substances into the active forms by their transfer onto a specific surface
      without the need of their prior dissolution.

PMID- 22870204
TI  - Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist
      medical care for chronic fatigue syndrome: a cost-effectiveness analysis.
AB  - BACKGROUND: The PACE trial compared the effectiveness of adding adaptive pacing
      therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy
      (GET), to specialist medical care (SMC) for patients with chronic fatigue
      syndrome. This paper reports the relative cost-effectiveness of these treatments
      in terms of quality adjusted life years (QALYs) and improvements in fatigue and
      physical function. METHODS: Resource use was measured and costs calculated.
      Healthcare and societal costs (healthcare plus lost production and unpaid
      informal care) were combined with QALYs gained, and changes in fatigue and
      disability; incremental cost-effectiveness ratios (ICERs) were computed. RESULTS:
      SMC patients had significantly lower healthcare costs than those receiving APT,
      CBT and GET. If society is willing to value a QALY at L30,000 there is a 62.7%
      likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that
      GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that
      SMC alone is most cost-effective. Compared to SMC alone, the incremental
      healthcare cost per QALY was L18,374 for CBT, L23,615 for GET and L55,235 for
      APT. From a societal perspective CBT has a 59.5% likelihood of being the most
      cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated
      SMC, while APT had a cost per QALY of L127,047. ICERs using reductions in fatigue
      and disability as outcomes largely mirrored these findings. CONCLUSIONS:
      Comparing the four treatments using a health care perspective, CBT had the
      greatest probability of being the most cost-effective followed by GET. APT had a
      lower probability of being the most cost-effective option than SMC alone. The
      relative cost-effectiveness was even greater from a societal perspective as
      additional cost savings due to reduced need for informal care were likely.

PMID- 22870205
TI  - Filamin A-hinge region 1-EGFP: a novel tool for tracking the cellular functions
      of filamin A in real-time.
AB  - BACKGROUND: Filamin A (FLNa) is an actin-crosslinking protein necessary for
      stabilizing the cell surface, organizing protrusive activity and for promoting
      efficient cellular translocation. Recently, our group demonstrated the
      requirement of FLNa for the internalization of the chemokine receptor CCR2B.
      METHODOLOGY AND PRINCIPAL FINDINGS: In order to study the role of FLNa in vitro
      and in real-time, we have developed a fluorescent FLNa-EGFP construct. In this
      novel imaging tool, we introduced the EGFP-tag inside the flexible hinge 1 region
      of FLNa between two calpain cleavage sites. Our findings indicate that the FLNa
      EGFP construct was correctly expressed, cleaved by calpain and colocalized with
      actin filaments as shown by immunostaining experiments in the human melanoma cell
      lines A7 (FLNa-repleted) and M2 (FLNa-deficient). In addition, scanning-electron
      microscopy (SEM) and micropatterning studies also provided clear evidence that
      the cell rigidity was restored. FLNa-EGFP allowed us to demonstrate the
      interaction of FLNa with the chemokine receptor CCR2B in endocytic vesicles after
      CCL2 ligand stimulation. Through live-cell imaging studies we show that the CCR2B
      receptor in Rab5-positive vesicles moves along filamin A-positive fibers.
      SIGNIFICANCE: Taken together, these results outline the functionality of the FLNa
      EGFP and the importance of filamin A for receptor internalization and movement
      into endocytic vesicles.

PMID- 22870206
TI  - Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during
      infection in natural hosts.
AB  - The Mycobacterium tuberculosis genome contains two large gene families encoding
      proteins of unknown function, characterized by conserved N-terminal proline and
      glutamate (PE and PPE) motifs. The presence of a large number of PE/PPE proteins
      with repetitive domains and evidence of strain variation has given rise to the
      suggestion that these proteins may play a role in immune evasion via antigenic
      variation, while emerging data suggests that some family members may play
      important roles in mycobacterial pathogenesis. In this study, we examined
      cellular immune responses to a panel of 36 PE/PPE proteins during human and
      bovine infection. We observed a distinct hierarchy of immune recognition,
      reflected both in the repertoire of PE/PPE peptide recognition in individual cows
      and humans and in the magnitude of IFN-gamma responses elicited by stimulation of
      sensitized host cells. The pattern of immunodominance was strikingly similar
      between cattle that had been experimentally infected with Mycobacterium bovis and
      humans naturally infected with clinical isolates of M. tuberculosis. The same
      pattern was maintained as disease progressed throughout a four-month course of
      infection in cattle, and between humans with latent as well as active
      tuberculosis. Detailed analysis of PE/PPE responses at the peptide level suggests
      that antigenic cross-reactivity amongst related family members is a major
      determinant in the observed differences in immune hierarchy. Taken together,
      these results demonstrate that a subset of PE/PPE proteins are major targets of
      the cellular immune response to tuberculosis, and are recognized at multiple
      stages of infection and in different disease states. Thus this work identifies a
      number of novel antigens that could find application in vaccine development, and
      provides new insights into PE/PPE biology.

PMID- 22870207
TI  - Withdrawal from cocaine self-administration alters NMDA receptor-mediated Ca2+
      entry in nucleus accumbens dendritic spines.
AB  - We previously showed that the time-dependent intensification ("incubation") of
      cue-induced cocaine seeking after withdrawal from extended-access cocaine self
      administration is accompanied by accumulation of Ca(2+)-permeable AMPA receptors
      (CP-AMPARs) in the rat nucleus accumbens (NAc). These results suggest an enduring
      change in Ca(2+) signaling in NAc dendritic spines. The purpose of the present
      study was to determine if Ca(2+) signaling via NMDA receptors (NMDARs) is also
      altered after incubation. Rats self-administered cocaine or saline for 10 days (6
      h/day). After 45-47 days of withdrawal, NMDAR-mediated Ca(2+) entry elicited by
      glutamate uncaging was monitored in individual NAc dendritic spines. NMDAR
      currents were simultaneously recorded using whole cell patch clamp recordings. We
      also measured NMDAR subunit levels in a postsynaptic density (PSD) fraction
      prepared from the NAc of identically treated rats. NMDAR currents did not differ
      between groups, but a smaller percentage of spines in the cocaine group responded
      to glutamate uncaging with NMDAR-mediated Ca(2+) entry. No significant group
      differences in NMDAR subunit protein levels were found. The decrease in the
      proportion of spines showing NMDAR-mediated Ca(2+) entry suggests that NAc
      neurons in the cocaine group contain more spines which lack NMDARs (non
      responding spines). The fact that cocaine and saline groups did not differ in
      NMDAR currents or NMDAR subunit levels suggests that the number of NMDARs on
      responding spines is not significantly altered by cocaine exposure. These
      findings are discussed in light of increases in dendritic spine density in the
      NAc observed after withdrawal from repeated cocaine exposure.

PMID- 22870208
TI  - Are there neurophenotypes for asthma? Functional brain imaging of the interaction
      between emotion and inflammation in asthma.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease noteworthy for its
      vulnerability to stress and emotion-induced symptom intensification. The fact
      that psychological stress and mood and anxiety disorders appear to increase
      expression of asthma symptoms suggests that neural signaling between the brain
      and lung at least partially modulates the inflammatory response and lung
      function. However, the precise nature of the neural pathways implicated in
      modulating asthma symptoms is unknown. Moreover, the extent to which variations
      in neural signaling predict different phenotypes of disease expression has not
      been studied. METHODS AND RESULTS: We used functional magnetic resonance imaging
      to measure neural signals in response to asthma-specific emotional cues,
      following allergen exposure, in asthmatics with a dual response to allergen
      challenge (significant inflammation), asthmatics with only an immediate response
      (minimal inflammation), and healthy controls. The anterior insular cortex was
      differentially activated by asthma-relevant cues, compared to general negative
      cues, during the development of the late phase of the dual response in
      asthmatics. Moreover, the degree of this differential activation predicted
      changes in airway inflammation. CONCLUSIONS: These findings indicate that
      neurophenotypes for asthma may be identifiable by neural reactivity of brain
      circuits known to be involved in processing emotional information. Those with
      greater activation in the anterior insula, in response to asthma-relevant
      psychological stimuli, exhibit greater inflammatory signals in the lung and
      increased severity of disease and may reflect a subset of asthmatics most
      vulnerable to the development of psychopathology. This approach offers an
      entirely new target for potential therapeutic intervention in asthma.

PMID- 22870211
TI  - Echinoderms display morphological and behavioural phenotypic plasticity in
      response to their trophic environment.
AB  - The trophic interactions of sea urchins are known to be the agents of phase
      shifts in benthic marine habitats such as tropical and temperate reefs. In
      temperate reefs, the grazing activity of sea urchins has been responsible for the
      destruction of kelp forests and the formation of 'urchin barrens', a rocky
      habitat dominated by crustose algae and encrusting invertebrates. Once formed,
      these urchin barrens can persist for decades. Trophic plasticity in the sea
      urchin may contribute to the stability and resilience of this alternate stable
      state by increasing diet breadth in sea urchins. This plasticity promotes
      ecological connectivity and weakens species interactions and so increases
      ecosystem stability. We test the hypothesis that sea urchins exhibit trophic
      plasticity using an approach that controls for other typically confounding
      environmental and genetic factors. To do this, we exposed a genetically
      homogenous population of sea urchins to two very different trophic environments
      over a period of two years. The sea urchins exhibited a wide degree of phenotypic
      trophic plasticity when exposed to contrasting trophic environments. The two
      populations developed differences in their gross morphology and the test
      microstructure. In addition, when challenged with unfamiliar prey, the response
      of each group was different. We show that sea urchins exhibit significant
      morphological and behavioural phenotypic plasticity independent of their
      environment or their nutritional status.

PMID- 22870209
TI  - Socioeconomic and nutritional factors account for the association of gastric
      cancer with Amerindian ancestry in a Latin American admixed population.
AB  - Gastric cancer is one of the most lethal types of cancer and its incidence varies
      worldwide, with the Andean region of South America showing high incidence rates.
      We evaluated the genetic structure of the population from Lima (Peru) and
      performed a case-control genetic association study to test the contribution of
      African, European, or Native American ancestry to risk for gastric cancer,
      controlling for the effect of non-genetic factors. A wide set of socioeconomic,
      dietary, and clinic information was collected for each participant in the study
      and ancestry was estimated based on 103 ancestry informative markers. Although
      the urban population from Lima is usually considered as mestizo (i.e., admixed
      from Africans, Europeans, and Native Americans), we observed a high fraction of
      Native American ancestry (78.4% for the cases and 74.6% for the controls) and a
      very low African ancestry (<5%). We determined that higher Native American
      individual ancestry is associated with gastric cancer, but socioeconomic factors
      associated both with gastric cancer and Native American ethnicity account for
      this association. Therefore, the high incidence of gastric cancer in Peru does
      not seem to be related to susceptibility alleles common in this population.
      Instead, our result suggests a predominant role for ethnic-associated
      socioeconomic factors and disparities in access to health services. Since Native
      Americans are a neglected group in genomic studies, we suggest that the
      population from Lima and other large cities from Western South America with high
      Native American ancestry background may be convenient targets for epidemiological
      studies focused on this ethnic group.

PMID- 22870210
TI  - Multiple sclerosis and CCSVI: a population-based case control study.
AB  - BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been
      associated to multiple sclerosis (MS). OBJECTIVE: To evaluate the possible
      association between CCSVI and MS, using a population-based control design.
      METHODS: A random cohort of 148 incident MS patients were enrolled in the study.
      We have also studied 20 patients with clinically isolated syndrome (CIS), 40
      patients with other neurological diseases (OND), and 172 healthy controls.
      Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects.
      A subject was considered CCSVI positive if >=2 venous hemodynamic criteria were
      fulfilled. RESULTS: CCSVI was present in 28 (18.9%) of the MS patients, in 2
      (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND
      patients. A significant association between MS and CCSVI was found with an odds
      ratio of 3.41 (95% confidence interval 1.63-7.13; p = 0.001). CCSVI was
      significantly more frequent among MS subjects with a disease duration longer than
      144 months (26.1% versus 12.6% of patients with duration shorter than 144 months;
      p = 0.03) and among patients with secondary progressive (SP) and primary
      progressive (PP) forms (30.2% and 29.4, respectively) than in patients with
      relapsing remitting (RR) MS (14.3%). A stronger association was found considering
      SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83-12.0, p = 0.001); the
      association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12
      5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI
      0.40-10.3; p = 0.4). CONCLUSIONS: A higher frequency of CCSVI has been found in
      MS patients; it was more evident in patients with advanced MS, suggesting that
      CCSVI could be related to MS disability.

PMID- 22870212
TI  - Detection of microbial translocation in HIV and SIV infection using the Limulus
      amebocyte lysate assay is masked by serum and plasma.
AB  - OBJECTIVE: Microbial translocation (MT) is thought to be a major contributor to
      the pathogenesis of HIV-related immune activation, and circulating
      lipopolysaccharide (LPS) from gram-negative bacteria is the principle measurement
      of this process. However, related research has been impeded by inconsistent LPS
      test results. METHODS: Specimens were obtained from HIV-infected adults enrolled
      in the PEARLS study (ACTG A5175) and HIV-HCV co-infected participants enrolled in
      a study of liver disease staging using MRI elastography. Pig-tailed macaque
      specimens were obtained from SIV-infected and -uninfected animals. Samples were
      tested for LPS using the LAL assay with diazo-coupling modifications to improve
      sensitive detection. RESULTS: When exogenous LPS was added to macaque plasma,
      >25% inhibition of LPS detection was found in 10/10 (100%) samples at 20% plasma
      concentration compared to control; in contrast 5/10 (50%) samples at 2% plasma
      concentration (p = 0.07) and 0/10 (0%) at 0.1% plasma concentration (p = 0.004)
      showed >25% inhibition of LPS detection. Similarly, when LPS was added to human
      serum, >25% inhibition of LPS detection was found in 5/12 (42%) of samples at 2%
      serum concentration compared to control, while 0/12 (0%) of samples in 0.1% serum
      showed >25% inhibition of LPS detection (p = 0.07). Likewise, LPS detection in
      human sera without exogenous LPS was improved by dilution: LPS was detected in
      2/12 (17%) human samples in 2% serum, ranging from 3,436-4,736 pg/mL, compared to
      9/12 (75%) samples in 0.1% serum, ranging from 123 pg/mL -60,131 pg/mL (p =
      0.016). In a separate validation cohort of HIV-HCV co-infected participants
      sampled at two different times on the same day, LPS measured in 0.2% plasma and
      with diazo-coupling was closely correlated between the first and second samples
      (R = 0.66, p<0.05). CONCLUSIONS: Undiluted serum and plasma mask LPS detection.
      The extent of MT may be substantially underestimated.

PMID- 22870213
TI  - Association of OX40L polymorphisms with sporadic breast cancer in northeast
      Chinese Han population.
AB  - OX40L is an important costimulatory molecule that plays a crucial role in the
      regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved
      in the pathogenesis of multiple autoimmune and inflammatory diseases such as
      systemic lupus erythematosus (SLE), carotid artery disease and cancer. The
      genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic
      sclerosis and show gender-specific effects in some studies. Accordingly, we
      performed a case-control study including 557 breast cancer patients and 580 age-
      and sex-matched healthy controls to investigate whether single nucleotide
      polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer
      susceptibility and progression in Chinese Han women. Seven SNPs of OX40L
      (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580)
      were genotyped with the method of polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele
      could increase the susceptibility to breast cancer (P = 0.009662), even in the
      validation study (P = 0.0001515). A significant association between rs3850641 and
      breast cancer risk was observed under the additive model and dominant model (P =
      0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype
      A(rs844648)A(rs10912580) was significantly associated with breast cancer, even
      after 10,000 permutations for haplotypes in block only (P = 0.0003). In
      clinicopathologic features analysis, the association between rs1234315 and C
      erbB2 status was significant (P = 0.02541). Our data primarily indicates that
      rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a
      northeast Chinese Han population.

PMID- 22870214
TI  - Potential formula for the calculation of starting and incremental insulin
      glargine doses: ALOHA subanalysis.
AB  - BACKGROUND: Pragmatic methods for dose optimization are required for the
      successful basal management in daily clinical practice. To derive a useful
      formula for calculating recommended glargine doses, we analyzed data from the Add
      on Lantus(r) to Oral Hypoglycemic Agents (ALOHA) study, a 24-week observation of
      Japanese type 2 diabetes patients. METHODOLOGY/PRINCIPAL FINDINGS: The patients
      who initiated insulin glargine in basal-supported oral therapy (BOT) regimen (n =
      3506) were analyzed. The correlations between average changes in glargine dose
      and HbA1c were calculated, and its regression formula was estimated from grouped
      data categorized by baseline HbA1c levels. Starting doses of the background
      subgroup achieving the HbA1c target with a last-observed dose above the average
      were compared to an assumed optimal starting dose of 0.15 U/kg/day. The
      difference in regression lines between background-subgroups was examined. A
      formula for determining the optimal starting and titration doses was thereby
      derived. The correlation coefficient between changes in dose and HbA1c was 
      0.9043. The estimated regression line formula was -0.964 * change in HbA1c+2.000.
      A starting dose of 0.15 U/kg/day was applicable to all background-subgroups
      except for patients with retinopathy (0.120 U/kg/day) and/or with eGFR<60
      mL/min/1.73 m(2) (0.114 U/kg/day). Additionally, women (0.135 U/kg/day) and
      patients with sulfonylureas (0.132 U/kg/day) received a slightly decreased
      starting dose. CONCLUSIONS/SIGNIFICANCE: We suggest a simplified and pragmatic
      dose calculation formula for type 2 diabetes patients starting glargine BOT
      optimal daily dose at 24 weeks  =  starting dose (0.15*weight) + incremental dose
      (baseline HbA1c - target HbA1c+2). This formula should be further validated using
      other samples in a prospective follow-up, especially since several patient groups
      required lower starting doses.

PMID- 22870215
TI  - Determinants of compliance behaviours among patients undergoing hemodialysis in
      Malaysia.
AB  - BACKGROUND: Patients with end stage renal disease often fail to follow prescribed
      dietary and fluid regimen, leading to undesirable outcomes. This study aimed to
      examine and identify factors influencing dietary, fluid, medication and dialysis
      compliance behaviours in patients undergoing hemodialysis. METHODS: This was a
      cross-sectional study which employed purposive sampling design. A total of 188
      respondents were recruited from 14 dialysis centres in Malaysia between 2008
      2011. Self-reported compliance behaviours and biochemical measurements were used
      as evaluation tools. RESULTS: Compliance rates of dietary, fluid, medication and
      dialysis were 27.7%, 24.5%, 66.5% and 91.0%, respectively. Younger, male, working
      patients and those with longer duration on hemodialysis were found more likely to
      be non-compliant. Lacks of adequate knowledge, inadequate self-efficacy skills,
      forgetfulness and financial constraints were the major perceived barriers towards
      better compliance to fluid, dietary, medication and dialysis, respectively.
      CONCLUSIONS: Healthcare professionals should recognise the factors hindering
      compliance from the patients' perspective while assisting them with appropriate
      skills in making necessary changes possible.

PMID- 22870216
TI  - Expression changes in the stroma of prostate cancer predict subsequent relapse.
AB  - Biomarkers are needed to address overtreatment that occurs for the majority of
      prostate cancer patients that would not die of the disease but receive radical
      treatment. A possible barrier to biomarker discovery may be the
      polyclonal/multifocal nature of prostate tumors as well as cell-type
      heterogeneity between patient samples. Tumor-adjacent stroma (tumor
      microenvironment) is less affected by genetic alteration and might therefore
      yield more consistent biomarkers in response to tumor aggressiveness. To this end
      we compared Affymetrix gene expression profiles in stroma near tumor and
      identified a set of 115 probe sets for which the expression levels were
      significantly correlated with time-to-relapse. We also compared patients that
      chemically relapsed shortly after prostatectomy (<1 year), and patients that did
      not relapse in the first four years after prostatectomy. We identified 131
      differentially expressed microarray probe sets between these two categories. 19
      probe sets (15 genes overlapped between the two gene lists with p<0.0001). We
      developed a PAM-based classifier by training on samples containing stroma near
      tumor: 9 rapid relapse patient samples and 9 indolent patient samples. We then
      tested the classifier on 47 different samples, containing 90% or more stroma. The
      classifier predicted the risk status of patients with an average accuracy of 87%.
      This is the first general tumor microenvironment-based prognostic classifier.
      These results indicate that the prostate cancer microenvironment exhibits
      reproducible changes useful for predicting outcomes for patients.

PMID- 22870218
TI  - Calcium availability influences litter size and sex ratio in white-footed mice
      (Peromyscus leucopus).
AB  - The production of offspring typically requires investment of resources derived
      from both the environment and maternal somatic reserves. As such, the
      availability of either of these types of resources has the potential to limit the
      degree to which resources are allocated to reproduction. Theory and empirical
      studies have argued that mothers modify reproductive performance relative to
      exogenous resource availability and maternal condition by adjusting size, number
      or sex of offspring produced. These relationships have classically been defined
      relative to availability of energy sources; however, in vertebrates, calcium also
      plays a critical role in offspring production, as a considerable amount of
      calcium is required to support the development of offspring skeleton(s). We
      tested whether the availability of calcium influences reproductive output by
      providing female white-footed mice with a low-calcium or standard diet from
      reproductive maturity to senescence. We then compared maternal skeletal condition
      and reproductive output, based on offspring mass, offspring number and litter sex
      ratio, between dietary treatments. Mothers on the low-calcium diet exhibited
      diminished skeletal condition at senescence and produced smaller and strongly
      female-biased litters. We show that skeletal condition and calcium intake can
      influence sex ratio and reproductive output following general theoretical models
      of resource partitioning during reproduction.

PMID- 22870217
TI  - Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in
      osteosarcoma.
AB  - Recently, there has been renewed interest in the role of tumor stem cells (TSCs)
      in tumorigenesis, chemoresistance, and relapse of malignant tumors including
      osteosarcoma. The potential exists to improve osteosarcoma treatment through
      characterization of TSCs and identification of therapeutic targets. Using
      transcriptome, proteome, immunophenotyping for cell-surface markers, and
      bioinformatic analyses, heterogeneous expression of previously reported TSC or
      osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4), NANOG, SOX2, and
      aldehyde dehydrogenase, among others, was observed in vitro. However,
      consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression
      in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed.
      In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma
      cultures was identified. ABCA5 was identified as a putative biomarker of TSCs
      and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic
      (5-azacytidine), anti-microtubule (vincristine), and anti-telomerase (3,11
      difluoro-6,8,13-trimethyl- 8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4)
      targeted therapeutic agents as candidates for TSC ablation in osteosarcoma.

PMID- 22870220
TI  - Magnetic forces and DNA mechanics in multiplexed magnetic tweezers.
AB  - Magnetic tweezers (MT) are a powerful tool for the study of DNA-enzyme
      interactions. Both the magnet-based manipulation and the camera-based detection
      used in MT are well suited for multiplexed measurements. Here, we systematically
      address challenges related to scaling of multiplexed magnetic tweezers (MMT)
      towards high levels of parallelization where large numbers of molecules (say
      10(3)) are addressed in the same amount of time required by a single-molecule
      measurement. We apply offline analysis of recorded images and show that this
      approach provides a scalable solution for parallel tracking of the xyz-positions
      of many beads simultaneously. We employ a large field-of-view imaging system to
      address many DNA-bead tethers in parallel. We model the 3D magnetic field
      generated by the magnets and derive the magnetic force experienced by DNA-bead
      tethers across the large field of view from first principles. We furthermore
      experimentally demonstrate that a DNA-bead tether subject to a rotating magnetic
      field describes a bicircular, Limacon rotation pattern and that an analysis of
      this pattern simultaneously yields information about the force angle and the
      position of attachment of the DNA on the bead. Finally, we apply MMT in the high
      throughput investigation of the distribution of the induced magnetic moment, the
      position of attachment of DNA on the beads, and DNA flexibility. The methods
      described herein pave the way to kilo-molecule level magnetic tweezers
      experiments.

PMID- 22870219
TI  - Quantification of uncoupling protein 2 reveals its main expression in immune
      cells and selective up-regulation during T-cell proliferation.
AB  - Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein. Although
      the protein was discovered in 1997, its function and even its tissue distribution
      are still under debate. Here we present a quantitative analysis of mRNA and
      protein expression in various mice tissues, revealing that UCP2 is mainly
      expressed in organs and cells associated with the immune system. Although the
      UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the
      protein was not detectable in neurons under physiological conditions. Instead, we
      could detect UCP2 in microglia, which act in the immune defense of the central
      nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2
      protein expression simultaneously to the increase in levels of other
      mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the
      selective increase of UCP2. The highest detected level of UCP2 expression in
      stimulated T-cells (0.54 ng/(ug total cellular protein)) was approximately 200
      times lower than the level of UCP1 in brown adipose tissue from room temperature
      acclimated mice. Both the UCP2 expression pattern and the time course of up
      regulation in stimulated T-cells imply UCP2's involvement in the immune response,
      probably by controlling the metabolism during cell proliferation.

PMID- 22870221
TI  - Two-photon compatibility and single-voxel, single-trial detection of subthreshold
      neuronal activity by a two-component optical voltage sensor.
AB  - Minimally invasive measurements of neuronal activity are essential for
      understanding how signal processing is performed by neuronal networks. While
      optical strategies for making such measurements hold great promise, optical
      sensors generally lack the speed and sensitivity necessary to record neuronal
      activity on a single-trial, single-neuron basis. Here we present additional
      biophysical characterization and practical improvements of a two-component
      optical voltage sensor (2cVoS), comprised of the neuronal tracer dye, DiO, and
      dipicrylamine (DiO/DPA). Using laser spot illumination we demonstrate that
      membrane potential-dependent fluorescence changes can be obtained in a wide
      variety of cell types within brain slices. We show a correlation between membrane
      labeling and the sensitivity of the magnitude of fluorescence signal, such that
      neurons with the brightest membrane labeling yield the largest DeltaF/F values
      per action potential (AP; ~40%). By substituting a blue-shifted donor for DiO we
      confirm that DiO/DPA works, at least in part, via a Forster resonance energy
      transfer (FRET) mechanism. We also describe a straightforward iontophoretic
      method for labeling multiple neurons with DiO and show that DiO/DPA is compatible
      with two-photon (2P) imaging. Finally, exploiting the high sensitivity of
      DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs) recorded from
      single spines of hippocampal pyramidal neurons and single-trial measurements of
      subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that
      the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage
      fluctuations with very high spatial and temporal resolution, properties well
      suited for monitoring electrical signals from multiple neurons within intact
      neuronal networks.

PMID- 22870222
TI  - Benzaldehyde thiosemicarbazone derived from limonene complexed with copper
      induced mitochondrial dysfunction in Leishmania amazonensis.
AB  - BACKGROUND: Leishmaniasis is a major health problem that affects more than 12
      million people. Treatment presents several problems, including high toxicity and
      many adverse effects, leading to the discontinuation of treatment and emergence
      of resistant strains. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the in vitro
      antileishmanial activity of benzaldehyde thiosemicarbazone derived from limonene
      complexed with copper, termed BenzCo, against Leishmania amazonensis. BenzCo
      inhibited the growth of the promastigote and axenic amastigote forms, with IC(50)
      concentrations of 3.8 and 9.5 uM, respectively, with 72 h of incubation.
      Intracellular amastigotes were inhibited by the compound, with an IC(50) of 10.7
      uM. BenzCo altered the shape, size, and ultrastructure of the parasites.
      Mitochondrial membrane depolarization was observed in protozoa treated with
      BenzCo but caused no alterations in the plasma membrane. Additionally, BenzCo
      induced lipoperoxidation and the production of mitochondrial superoxide anion
      radicals in promastigotes and axenic amastigotes of Leishmania amazonensis.
      CONCLUSION/SIGNIFICANCE: Our studies indicated that the antileishmania activity
      of BenzCo might be associated with mitochondrial dysfunction and oxidative
      damage, leading to parasite death.

PMID- 22870223
TI  - Evolution of space dependent growth in the teleost Astyanax mexicanus.
AB  - The relationship between growth rate and environmental space is an unresolved
      issue in teleosts. While it is known from aquaculture studies that stocking
      density has a negative relationship to growth, the underlying mechanisms have not
      been elucidated, primarily because the growth rate of populations rather than
      individual fish were the subject of all previous studies. Here we investigate
      this problem in the teleost Astyanax mexicanus, which consists of a sighted
      surface-dwelling form (surface fish) and several blind cave-dwelling (cavefish)
      forms. Surface fish and cavefish are distinguished by living in spatially
      contrasting environments and therefore are excellent models to study the effects
      of environmental size on growth. Multiple controlled growth experiments with
      individual fish raised in confined or unconfined spaces showed that environmental
      size has a major impact on growth rate in surface fish, a trait we have termed
      space dependent growth (SDG). In contrast, SDG has regressed to different degrees
      in the Pachon and Tinaja populations of cavefish. Mating experiments between
      surface and Pachon cavefish show that SDG is inherited as a dominant trait and is
      controlled by multiple genetic factors. Despite its regression in blind cavefish,
      SDG is not affected when sighted surface fish are raised in darkness, indicating
      that vision is not required to perceive and react to environmental space.
      Analysis of plasma cortisol levels showed that an elevation above basal levels
      occurred soon after surface fish were exposed to confined space. This initial
      cortisol peak was absent in Pachon cavefish, suggesting that the effects of
      confined space on growth may be mediated partly through a stress response. We
      conclude that Astyanax reacts to confined spaces by exhibiting SDG, which has a
      genetic component and shows evolutionary regression during adaptation of cavefish
      to confined environments.

PMID- 22870224
TI  - A high-throughput forward genetic screen identifies genes required for virulence
      of Pseudomonas syringae pv. maculicola ES4326 on Arabidopsis.
AB  - Successful pathogenesis requires a number of coordinated processes whose genetic
      bases remain to be fully characterized. We utilized a high-throughput, liquid
      media-based assay to screen transposon disruptants of the phytopathogen
      Pseudomonas syringae pv. maculicola ES4326 to identify genes required for
      virulence on Arabidopsis. Many genes identified through this screen were involved
      in processes such as type III secretion, periplasmic glucan biosynthesis,
      flagellar motility, and amino acid biosynthesis. A small set of genes did not
      fall into any of these functional groups, and their disruption resulted in
      context-specific effects on in planta bacterial growth.

PMID- 22870225
TI  - Evidence that the density of self peptide-MHC ligands regulates T-cell receptor
      signaling.
AB  - Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell
      receptor (TCR) and are always in a large access over the cognate pMHC on the
      surface of antigen presenting cells. We assembled soluble cognate and noncognate
      pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into
      oligomers that mimic pMHC clustering and examined how multivalency and density of
      the pMHCs in model clusters influences the binding to live CD8 T cells and the
      kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I
      proteins promotes their interaction with CD8 co-receptor, which plays a critical
      role in recognition of a small number of cognate pMHC-I ligands. This suggests
      that MHC clustering on live target cells could be utilized as a sensitive
      mechanism to regulate T cell responsiveness.

PMID- 22870226
TI  - Deep Panning: steps towards probing the IgOme.
AB  - BACKGROUND: Polyclonal serum consists of vast collections of antibodies, products
      of differentiated B-cells. The spectrum of antibody specificities is dynamic and
      varies with age, physiology, and exposure to pathological insults. The complete
      repertoire of antibody specificities in blood, the IgOme, is therefore an
      extraordinarily rich source of information-a molecular record of previous
      encounters as well as a status report of current immune activity. The ability to
      profile antibody specificities of polyclonal serum at exceptionally high
      resolution has been an important and serious challenge which can now be overcome.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we illustrate the application of Deep
      Panning, a method that combines the flexibility of combinatorial phage display of
      random peptides with the power of high-throughput deep sequencing. Deep Panning
      is first applied to evaluate the quality and diversity of naive random peptide
      libraries. The production of very large data sets, hundreds of thousands of
      peptides, has revealed unexpected properties of combinatorial random peptide
      libraries and indicates correctives to ensure the quality of the libraries
      generated. Next, Deep Panning is used to analyze a model monoclonal antibody in
      addition to allowing one to follow the dynamics of biopanning and peptide
      selection. Finally Deep Panning is applied to profile polyclonal sera derived
      from HIV infected individuals. CONCLUSIONS/SIGNIFICANCE: The ability to generate
      and characterize hundreds of thousands of affinity-selected peptides creates an
      effective means towards the interrogation of the IgOme and understanding of the
      humoral response to disease. Deep Panning should open the door to new
      possibilities for serological diagnostics, vaccine design and the discovery of
      the correlates of immunity to emerging infectious agents.

PMID- 22870227
TI  - Landscape structure shapes habitat finding ability in a butterfly.
AB  - Land-use intensification and habitat fragmentation is predicted to impact on the
      search strategies animals use to find habitat. We compared the habitat finding
      ability between populations of the speckled wood butterfly (Pararge aegeria L.)
      from landscapes that differ in degree of habitat fragmentation. Naive butterflies
      reared under standardized laboratory conditions but originating from either
      fragmented agricultural landscapes or more continuous forested landscapes were
      released in the field, at fixed distances from a target habitat patch, and their
      flight paths were recorded. Butterflies originating from fragmented agricultural
      landscapes were better able to find a woodlot habitat from a distance compared to
      conspecifics from continuous forested landscapes. To manipulate the access to
      olfactory information, a subset of individuals from both landscape types were
      included in an antennae removal experiment. This confirmed the longer perceptual
      range for butterflies from agricultural landscapes and indicated the significance
      of both visual and olfactory information for orientation towards habitat. Our
      results are consistent with selection for increased perceptual range in
      fragmented landscapes to reduce dispersal costs. An increased perceptual range
      will alter the functional connectivity and thereby the chances for population
      persistence for the same level of structural connectivity in a fragmented
      landscape.

PMID- 22870229
TI  - Sight or scent: lemur sensory reliance in detecting food quality varies with
      feeding ecology.
AB  - Visual and olfactory cues provide important information to foragers, yet we know
      little about species differences in sensory reliance during food selection. In a
      series of experimental foraging studies, we examined the relative reliance on
      vision versus olfaction in three diurnal, primate species with diverse feeding
      ecologies, including folivorous Coquerel's sifakas (Propithecus coquereli),
      frugivorous ruffed lemurs (Varecia variegata spp), and generalist ring-tailed
      lemurs (Lemur catta). We used animals with known color-vision status and foods
      for which different maturation stages (and hence quality) produce distinct visual
      and olfactory cues (the latter determined chemically). We first showed that
      lemurs preferentially selected high-quality foods over low-quality foods when
      visual and olfactory cues were simultaneously available for both food types.
      Next, using a novel apparatus in a series of discrimination trials, we either
      manipulated food quality (while holding sensory cues constant) or manipulated
      sensory cues (while holding food quality constant). Among our study subjects that
      showed relatively strong preferences for high-quality foods, folivores required
      both sensory cues combined to reliably identify their preferred foods, whereas
      generalists could identify their preferred foods using either cue alone, and
      frugivores could identify their preferred foods using olfactory, but not visual,
      cues alone. Moreover, when only high-quality foods were available, folivores and
      generalists used visual rather than olfactory cues to select food, whereas
      frugivores used both cue types equally. Lastly, individuals in all three of the
      study species predominantly relied on sight when choosing between low-quality
      foods, but species differed in the strength of their sensory biases. Our results
      generally emphasize visual over olfactory reliance in foraging lemurs, but we
      suggest that the relative sensory reliance of animals may vary with their feeding
      ecology.

PMID- 22870228
TI  - A novel volume-age-KPS (VAK) glioblastoma classification identifies a prognostic
      cognate microRNA-gene signature.
AB  - BACKGROUND: Several studies have established Glioblastoma Multiforme (GBM)
      prognostic and predictive models based on age and Karnofsky Performance Status
      (KPS), while very few studies evaluated the prognostic and predictive
      significance of preoperative MR-imaging. However, to date, there is no simple
      preoperative GBM classification that also correlates with a highly prognostic
      genomic signature. Thus, we present for the first time a biologically relevant,
      and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM
      classification that can easily and non-invasively be determined upon patient
      admission. METHODS: We quantitatively analyzed the volumes of 78 GBM patient MRIs
      present in The Cancer Imaging Archive (TCIA) corresponding to patients in The
      Cancer Genome Atlas (TCGA) with VAK annotation. The variables were then combined
      using a simple 3-point scoring system to form the VAK classification. A
      validation set (N = 64) from both the TCGA and Rembrandt databases was used to
      confirm the classification. Transcription factor and genomic correlations were
      performed using the gene pattern suite and Ingenuity Pathway Analysis. RESULTS:
      VAK-A and VAK-B classes showed significant median survival differences in
      discovery (P = 0.007) and validation sets (P = 0.008). VAK-A is significantly
      associated with P53 activation, while VAK-B shows significant P53 inhibition.
      Furthermore, a molecular gene signature comprised of a total of 25 genes and
      microRNAs was significantly associated with the classes and predicted survival in
      an independent validation set (P = 0.001). A favorable MGMT promoter methylation
      status resulted in a 10.5 months additional survival benefit for VAK-A compared
      to VAK-B patients. CONCLUSIONS: The non-invasively determined VAK classification
      with its implication of VAK-specific molecular regulatory networks, can serve as
      a very robust initial prognostic tool, clinical trial selection criteria, and
      important step toward the refinement of genomics-based personalized therapy for
      GBM patients.

PMID- 22870230
TI  - Private and public decisions in social dilemmas: evidence from children's
      behavior.
AB  - Are selfish impulses less likely to be pursued when decisions are publicly
      observable? Is the presence of peers a potential solution to social dilemmas? In
      this paper we report data on the self-control decisions of children aged 6 to 11
      who participated in games that require one to resist a selfish impulse for
      several minutes in order to benefit others. In Public Condition children make
      decisions in public view of the group of other participants, while in Private
      Condition they have the possibility to decide privately. We find that children
      aged 9 and higher are better able to resist selfish impulses in public
      environments. Younger children, however, display no such effect. Further, we find
      self-control substantially impacted by group size. When decisions are public,
      self-control is better in larger groups, while in private condition the opposite
      holds.

PMID- 22870231
TI  - Regulation and gene expression profiling of NKG2D positive human cytomegalovirus
      primed CD4+ T-cells.
AB  - NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8(+) T
      cells, and gammadelta T-cells. NKG2D expression is normally absent from CD4(+) T
      cells, however recently a subset of NKG2D(+) CD4(+) T-cells has been found, which
      is specific for human cytomegalovirus (HCMV). This particular subset of HCMV
      specific NKG2D(+) CD4(+) T-cells possesses effector-like functions, thus
      resembling the subsets of NKG2D(+) CD4(+) T-cells found in other chronic
      inflammations. However, the precise mechanism leading to NKG2D expression on HCMV
      specific CD4(+) T-cells is currently not known. In this study we used genome-wide
      analysis of individual genes and gene set enrichment analysis (GSEA) to
      investigate the gene expression profile of NKG2D(+) CD4(+) T-cells, generated
      from HCMV-primed CD4(+) T-cells. We show that the HCMV-primed NKG2D(+) CD4(+) T
      cells possess a higher differentiated phenotype than the NKG2D(-) CD4(+) T-cells,
      both at the gene expression profile and cytokine profile. The ability to express
      NKG2D at the cell surface was primarily determined by the activation or
      differentiation status of the CD4(+) T-cells and not by the antigen presenting
      cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+)
      T-cells following HCMV stimulation. However, knock-down of CD94 did not affect
      NKG2D cell surface expression or signaling. In addition, we show that NKG2D is
      recycled at the cell surface of activated CD4(+) T-cells, whereas it is produced
      de novo in resting CD4(+) T-cells. These findings provide novel information about
      the gene expression profile of HCMV-primed NKG2D(+) CD4(+) T-cells, as well as
      the mechanisms regulating NKG2D cell surface expression.

PMID- 22870232
TI  - Dynamic modulation of DNA replication and gene transcription in deep-sea
      filamentous phage SW1 in response to changes of host growth and temperature.
AB  - Little is known about the response of deep-sea virus and their relationship with
      their host towards environmental change. Although viruses are thought to play key
      roles in the deep-sea ecological evolution and biogeochemical cycling, these
      roles are yet to be defined. This study aims to delineate the relationship
      between a deep-sea filamentous phage SW1 and its host Shewanella piezotolerans
      (S. piezotolerans) WP3, and their response towards temperature change. The copy
      number of SW1's replicative form (RF-) DNA and single-stranded (ss-) DNA along
      the different growth phases of WP3 were quantified at 20 degrees C and 4 degrees
      C, respectively. The copy number of SW1 RF-DNA was found to be temperature and
      growth phase-dependent, while the ssDNA of SW1 was only produced at 4 degrees C.
      This is the first report showing low-temperature dependence of phage DNA
      replication. The transcription of SW1 key genes fpsA and fpsR were also found to
      be induced at low temperature during all the monitored growth periods of WP3.
      Additionally, the transcription of SW1 was found to be induced by cold-shock
      while its DNA replication was not changed. Our data demonstrates a dynamic change
      of virus DNA replication and transcription in accordance with host growth, and
      the low temperature adapted mechanisms for SW1 activities in the deep sea. This
      low temperature adapted deep-sea virus-bacterium system could serve as an ideal
      model to further study the mechanism and relationship of deep-sea virus-bacteria
      ecosystems.

PMID- 22870233
TI  - Functional synergies underlying control of upright posture during changes in head
      orientation.
AB  - BACKGROUND: Studies of human upright posture typically have stressed the need to
      control ankle and hip joints to achieve postural stability. Recent studies,
      however, suggest that postural stability involves multi degree-of-freedom (DOF)
      coordination, especially when performing supra-postural tasks. This study
      investigated kinematic synergies related to control of the body's position in
      space (two, four and six DOF models) and changes in the head's orientation (six
      DOF model). METHODOLOGY/PRINCIPAL FINDINGS: Subjects either tracked a vertically
      moving target with a head-mounted laser pointer or fixated a stationary point
      during 4-min trials. Uncontrolled manifold (UCM) analysis was performed across
      tracking cycles at each point in time to determine the structure of joint
      configuration variance related to postural stability or tracking consistency. The
      effect of simulated removal of covariance among joints on that structure was
      investigated to further determine the role of multijoint coordination. Results
      indicated that cervical joint motion was poorly coordinated with other joints to
      stabilize the position of the body center of mass (CM). However, cervical joints
      were coordinated in a flexible manner with more caudal joints to achieve
      consistent changes in head orientation. CONCLUSIONS/SIGNIFICANCE: An
      understanding of multijoint coordination requires reference to the
      stability/control of important performance variables. The nature of that
      coordination differs depending on the reference variable. Stability of upright
      posture primarily involved multijoint coordination of lower extremity and lower
      trunk joints. Consistent changes in the orientation of the head, however,
      required flexible coordination of those joints with motion of the cervical spine.
      A two-segment model of postural control was unable to account for the observed
      stability of the CM position during the tracking task, further supporting the
      need to consider multijoint coordination to understand postural stability.

PMID- 22870234
TI  - Informing evidence-based decision-making for patients with comorbidity:
      availability of necessary information in clinical trials for chronic diseases.
AB  - BACKGROUND: The population with multiple chronic conditions is growing. Prior
      studies indicate that patients with comorbidities are frequently excluded from
      trials but do not address whether information is available in trials to draw
      conclusions about treatment effects for these patients. METHODS AND FINDINGS: We
      conducted a literature survey of trials from 11 Cochrane Reviews for four chronic
      diseases (diabetes, heart failure, chronic obstructive pulmonary disease, and
      stroke). The Cochrane Reviews systematically identified and summarized trials on
      the effectiveness of diuretics, metformin, anticoagulants, longacting beta
      agonists alone or in combination with inhaled corticosteroids, lipid lowering
      agents, exercise and diet. Eligible studies were reports of trials included in
      the Cochrane reviews and additional papers that described the methods of these
      trials. We assessed the exclusion and inclusion of people with comorbidities, the
      reporting of comorbidities, and whether comorbidities were considered as
      potential modifiers of treatment effects. Overall, the replicability of both the
      inclusion criteria (mean [standard deviation (SD)]: 6.0 (2.1), range (min-max): 1
      9.5) and exclusion criteria (mean(SD): 5.3 (2.1), range: 1-9.5) was only
      moderate. Trials excluded patients with many common comorbidities. The proportion
      of exclusions for comorbidities ranged from 0-42 percent for heart failure, 0-55
      percent for COPD, 0-44 percent for diabetes, and 0-39 percent for stroke. Seventy
      of the 161 trials (43.5%) described the prevalence of any comorbidity among
      participants with the index disease. The reporting of comorbidities in trials was
      very limited, in terms of reporting an operational definition and method of
      ascertainment for the presence of comorbidity and treatments for the comorbidity.
      It was even less common that the trials assessed whether comorbidities were
      potential modifiers of treatment effects. CONCLUSIONS: Comorbidities receive
      little attention in chronic disease trials. Given the public health importance of
      people with multiple chronic conditions, trials should better report on
      comorbidities and assess the effect comorbidities have on treatment outcomes.

PMID- 22870235
TI  - Bacterial community shift in treated periodontitis patients revealed by ion
      torrent 16S rRNA gene amplicon sequencing.
AB  - Periodontitis, one of the most common diseases in the world, is caused by a
      mixture of pathogenic bacteria and inflammatory host responses and often treated
      by antimicrobials as an adjunct to scaling and root planing (SRP). Our study aims
      to elucidate explorative and descriptive temporal shifts in bacterial communities
      between patients treated by SRP alone versus SRP plus antibiotics. This is the
      first metagenomic study using an Ion Torrent Personal Genome Machine (PGM). Eight
      subgingival plaque samples from four patients with chronic periodontitis, taken
      before and two months after intervention were analyzed. Amplicons from the V6
      hypervariable region of the 16S rRNA gene were generated and sequenced each on a
      314 chip. Sequencing reads were clustered into operational taxonomic units (OTUs,
      3% distance), described by community metrics, and taxonomically classified. Reads
      ranging from 599,933 to 650,416 per sample were clustered into 1,648 to 2,659 non
      singleton OTUs, respectively. Increased diversity (Shannon and Simpson) in all
      samples after therapy was observed regardless of the treatment type whereas
      richness (ACE) showed no correlation. Taxonomic analysis revealed different
      microbial shifts between both therapy approaches at all taxonomic levels. Most
      remarkably, the genera Porphyromonas, Tannerella, Treponema, and Filifactor all
      harboring periodontal pathogenic species were removed almost only in the group
      treated with SPR and antibiotics. For the species T. forsythia and P. gingivalis
      results were corroborated by real-time PCR analysis. In the future, hypothesis
      free metagenomic analysis could be the key in understanding polymicrobial
      diseases and be used for therapy monitoring. Therefore, as read length continues
      to increase and cost to decrease, rapid benchtop sequencers like the PGM might
      finally be used in routine diagnostic.

PMID- 22870236
TI  - Patterns of genetic variation across altitude in three plant species of semi-dry
      grasslands.
AB  - BACKGROUND: Environmental gradients caused by altitudinal gradients may affect
      genetic variation within and among plant populations and inbreeding within
      populations. Populations in the upper range periphery of a species may be
      important source populations for range shifts to higher altitude in response to
      climate change. In this study we investigate patterns of population genetic
      variation at upper peripheral and lower more central altitudes in three common
      plant species of semi-dry grasslands in montane landscapes. METHODOLOGY/PRINCIPAL
      FINDINGS: In Briza media, Trifolium montanum and Ranunculus bulbosus genetic
      diversity, inbreeding and genetic relatedness of individuals within populations
      and genetic differentiation among populations was characterized using AFLP
      markers. Populations were sampled in the Swiss Alps at 1800 (upper periphery of
      the study organisms) and at 1200 m a.s.l. Genetic diversity was not affected by
      altitude and only in B. media inbreeding was greater at higher altitudes. Genetic
      differentiation was slightly greater among populations at higher altitudes in B.
      media and individuals within populations were more related to each other compared
      to individuals in lower altitude populations. A similar but less strong pattern
      of differentiation and relatedness was observed in T. montanum, while in R.
      bulbosus there was no effect of altitude. Estimations of population size and
      isolation of populations were similar, both at higher and lower altitudes.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that altitude does not affect
      genetic diversity in the grassland species under study. Genetic differentiation
      of populations increased only slightly at higher elevation, probably due to
      extensive (historic) gene flow among altitudes. Potentially pre-adapted genes
      might therefore spread easily across altitudes. Our study indicates that
      populations at the upper periphery are not genetically depauperate or isolated
      and thus may be important source populations for migration under climate change.

PMID- 22870237
TI  - Interaction of hydrogen sulfide and estrogen on the proliferation of vascular
      smooth muscle cells.
AB  - Hydrogen sulfide (H(2)S) can be endogenously generated from cystathionine gamma
      lyase (CSE) in cardiovascular system, offering a cardiovascular protection. It is
      also known that the lower risk of cardiovascular diseases in female is partially
      attributed to the protective effect of estrogen. The current study explores the
      interaction of H(2)S and estrogen on smooth muscle cell (SMC) growth. In the
      present study, we found that the proliferation of cultured vascular SMCs isolated
      from wild-type mice (WT-SMCs) was inhibited, but that from CSE gene knockout mice
      (CSE-KO-SMCs) increased, by estrogen treatments. The expression of estrogen
      receptor alpha (ERalpha), but not ERbeta, was significantly decreased in CSE-KO
      SMCs compared with that in WT-SMCs. Exogenously applied H(2)S markedly increased
      ERalpha but not ERbeta expression. In addition, the inhibition of ER activation
      and knockdown of ERalpha expression in WT-SMCs or the overexpression of ERalpha
      in CSE-KO-SMCs reversed the respective effects of estrogen on cell proliferation.
      The expression of cyclin D1 was reduced in WT-SMCs but increased in CSE-KO-SMCs
      after estrogen treatments, which was reversed by knockdown of ERalpha in WT-SMCs
      or overexpression of ERalpha in CSE-KO-SMCs, respectively. The overexpression of
      cyclin D1 in WT-SMCs or knockdown of cyclin D1 expression in CSE-KO-SMCs reversed
      the effects of estrogen on cell proliferation. These results suggest that H(2)S
      mediates estrogen-inhibited proliferation of SMCs via selective activation of
      ERalpha/cyclin D1 pathways.

PMID- 22870238
TI  - Effect of preventive supplementation with zinc and other micronutrients on non
      malarial morbidity in Tanzanian pre-school children: a randomized trial.
AB  - BACKGROUND: The efficacy of preventive zinc supplementation against diarrhea and
      respiratory illness may depend on simultaneous supplementation with other
      micronutrients. We aimed to assess the effect of supplementation with zinc and
      multiple micronutrients on diarrhea and other causes of non-malarial morbidity.
      METHODS AND FINDINGS: Rural Tanzanian children (n = 612) aged 6-60 months and
      with height-for-age z-score < -1.5 SD were randomized to daily supplementation
      with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc,
      or placebo. Children were followed for an average of 45 weeks. During follow-up,
      we recorded morbidity episodes. We found no evidence that concurrent
      supplementation with multi-nutrients influenced the magnitude of the effect of
      zinc on rates of diarrhea, respiratory illness, fever without localizing signs,
      or other illness (guardian-reported illness with symptoms involving skin, ears,
      eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced
      the hazard rate of diarrhea by 24% (4%-40%). By contrast, multi-nutrients seemed
      to increase this rate (HR; 95% CI: 1.19; 0.94-1.50), particularly in children
      with asymptomatic Giardia infection at baseline (2.03; 1.24-3.32). Zinc also
      protected against episodes of fever without localizing signs (0.75; 0.57-0.96),
      but we found no evidence that it reduced the overall number of clinic visits.
      CONCLUSIONS: We found no evidence that the efficacy of zinc supplements in
      reducing diarrhea rates is enhanced by concurrent supplementation with other
      micronutrients. By reducing rates of fever without localizing signs,
      supplementation with zinc may reduce inappropriate drug use with anti-malarial
      medications and antibiotics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00623857.

PMID- 22870239
TI  - The comparative clinical course of pregnant and non-pregnant women hospitalised
      with influenza A(H1N1)pdm09 infection.
AB  - INTRODUCTION: The Influenza Clinical Information Network (FLU-CIN) was
      established to gather detailed clinical and epidemiological information about
      patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This
      report focuses on the clinical course and outcomes of infection in pregnancy.
      METHODS: A standardised data extraction form was used to obtain detailed clinical
      information from hospital case notes and electronic records, for patients with
      PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five
      clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009
      and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women
      aged 15-44 years, using univariate and multivariable techniques. RESULTS: Of the
      395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or
      third trimester. Pregnant women were significantly less likely to exhibit severe
      respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30-0.82)),
      require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20-0.80)), or have
      underlying co-morbidities (p-trend <0.001). However, they were equally likely to
      be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to
      die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46
      1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical
      ventilation and three died. CONCLUSIONS: Since the expected prevalence of
      pregnancy in the source population was 6%, our data suggest that pregnancy
      greatly increased the likelihood of hospital admission with A(H1N1)pdm09.
      Pregnant women were less likely than non-pregnant women to have respiratory
      distress on admission, but severe outcomes were equally likely in both groups.

PMID- 22870240
TI  - Hypersensitivity in borderline personality disorder during mindreading.
AB  - BACKGROUND: One of the core symptoms of borderline personality disorder (BPD) is
      the instability in interpersonal relationships. This might be related to existent
      differences in mindreading between BPD patients and healthy individuals. METHODS:
      We examined the behavioural and neurophysiological (fMRI) responses of BPD
      patients and healthy controls (HC) during performance of the 'Reading the Mind in
      the Eyes' test (RMET). RESULTS: Mental state discrimination was significantly
      better and faster for affective eye gazes in BPD patients than in HC. At the
      neurophysiological level, this was manifested in a stronger activation of the
      amygdala and greater activity of the medial frontal gyrus, the left temporal pole
      and the middle temporal gyrus during affective eye gazes. In contrast, HC
      subjects showed a greater activation in the insula and the superior temporal
      gyri. CONCLUSION: These findings indicate that BPD patients are highly vigilant
      to social stimuli, maybe because they resonate intuitively with mental states of
      others.

PMID- 22870241
TI  - High-throughput genotyping in metastatic esophageal squamous cell carcinoma
      identifies phosphoinositide-3-kinase and BRAF mutations.
AB  - BACKGROUND: Given the high incidence of metastatic esophageal squamous cell
      carcinoma, especially in Asia, we screened for the presence of somatic mutations
      using OncoMap platform with the aim of defining subsets of patients who may be
      potential candidate for targeted therapy. METHODS AND MATERIALS: We analyzed 87
      tissue specimens obtained from 80 patients who were pathologically confirmed with
      esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based
      chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to
      interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens
      were prepared from primary cancer sites in 70 patients and from metastatic sites
      in 17 patients. In order to test the concordance between primary and metastatic
      sites from the patient for mutations, we analyzed 7 paired (primary-metastatic)
      specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor
      content was >70%. RESULTS: In total, we have detected 20 hotspot mutations out of
      80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K,
      five H1047R and one H1047L) (N = 10, 11.5%) followed by MLH1 V384D (N = 7, 8.0%),
      TP53 (R306, R175H and R273C) (N = 3, 3.5%), BRAF V600E (N = 1, 1.2%), CTNNB1 D32N
      (N = 1, 1.2%), and EGFR P733L (N = 1, 1.2%). Distributions of somatic mutations
      were not different according to anatomic sites of esophageal cancer
      (cervical/upper, mid, lower). In addition, there was no difference in frequency
      of mutations between primary-metastasis paired samples. CONCLUSIONS: Our study
      led to the detection of potentially druggable mutations in esophageal SCC which
      may guide novel therapies in small subsets of esophageal cancer patients.

PMID- 22870242
TI  - Recent trends in the incidence of anxiety diagnoses and symptoms in primary care.
AB  - BACKGROUND: Anxiety is common, with significant morbidity, but little is known
      about presentations and recording of anxiety diagnoses and symptoms in primary
      care. This study aimed to determine trends in incidence and socio-demographic
      variation in General Practitioner (GP) recorded diagnoses of anxiety, mixed
      anxiety/depression, panic and anxiety symptoms. METHODOLOGY/PRINCIPAL FINDINGS:
      Annual incidence rates of anxiety diagnoses and symptoms were calculated from 361
      UK general practices contributing to The Health Improvement Network (THIN)
      database between 1998 and 2008, adjusted for year of diagnosis, gender, age, and
      deprivation. Incidence of GP recorded anxiety diagnosis fell from 7.9 to
      4.9/1000PYAR from 1998 to 2008, while incidence of anxiety symptoms rose from 3.9
      to 5.8/1000PYAR. Incidence of mixed anxiety/depression fell from 4.0 to
      2.2/1000PYAR, and incidence of panic disorder fell from 0.9/1000PYAR in 1998 to
      0.5/1000PYAR in 2008. All these entries were approximately twice as common in
      women and more common in deprived areas. GP-recorded anxiety diagnoses, symptoms
      and mixed anxiety/depression were commonest aged 45-64 years, whilst panic
      disorder/attacks were more common in those 16-44 years. GPs predominately use
      broad non-specific codes to record anxiety problems in the UK.
      CONCLUSIONS/SIGNIFICANCE: GP recording of anxiety diagnoses has fallen whilst
      recording of anxiety symptoms has increased over time. The incidence of GP
      recorded diagnoses of anxiety diagnoses was lower than in screened populations in
      primary care. The reasons for this apparent under-recording and whether it
      represents under-detection in those being seen, a reluctance to report anxiety to
      their GP, or a reluctance amongst GPs to label people with anxiety requires
      investigation.

PMID- 22870243
TI  - In vitro study of cerebrospinal fluid dynamics in a shaken basal cistern after
      experimental subarachnoid hemorrhage.
AB  - BACKGROUND: Cerebral arterial vasospasm leads to delayed cerebral ischemia and
      constitutes the major delayed complication following aneurysmal subarachnoid
      hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from
      the subarachnoid space. Clinical pilot studies allow the hypothesis that the
      clearance of subarachnoid blood is facilitated by means of head shaking. A major
      obstacle for meaningful clinical studies is the lack of data on appropriate
      parameters of head shaking. Our in vitro study aims to provide these essential
      parameters. METHODOLOGY/PRINCIPAL FINDINGS: A model of the basal cerebral cistern
      was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage
      was simulated by addition of dyed experimental blood to transparent experimental
      cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern.
      Effects of various head positions and head motion settings (shaking angle
      amplitudes and shaking frequencies) on blood clearance were investigated using
      the quantitative dye washout method. Blood washout can be divided into two
      phases: Blood/CSF mixing and clearance. The major effect of shaking consists in
      better mixing of blood and CSF thereby increasing clearance rate. Without
      shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are
      hampered by differences in density and viscosity of blood and CSF. Blood
      clearance increases with decreased shaking frequency and with increased shaking
      angle amplitude. Head shaking facilitates clearance by varying the direction of
      gravitational force. CONCLUSIONS/SIGNIFICANCE: From this in vitro study can be
      inferred that patient or head shaking with large shaking angles at low frequency
      is a promising therapeutic strategy to increase blood clearance from the
      subarachnoid space.

PMID- 22870244
TI  - First diagnostic marine reptile remains from the Aalenian (Middle Jurassic): a
      new ichthyosaur from southwestern Germany.
AB  - BACKGROUND: The Middle Jurassic was a critical time in the evolutionary history
      of ichthyosaurs. During this time interval, the diverse, well-studied faunas of
      the Lower Jurassic were entirely replaced by ophthalmosaurids, a new group that
      arose sometime prior to the Aalenian-Bajocian boundary and by the latest middle
      Jurassic comprised the only surviving group of ichthyosaurs. Thus, the Middle
      Jurassic Aalenian-Bathonian interval (176-165 million years ago) comprises the
      time frame during which ophthalmosaurids not only originated but also achieved
      taxonomic dominance. However, diagnostic ichthyosaur remains have been described
      previously from only a single locality from this interval, from the Bajocian of
      Argentina. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we describe a new
      species of ichthyosaur based on a partial articulated specimen from the Middle
      Jurassic of southwestern Germany. This specimen was recovered from the
      Opalinuston Formation (early Aalenian) and is referable to Stenopterygius
      aaleniensis sp. nov. reflecting features of the skull and forefin. The genus
      Stenopterygius is diverse and abundant in the Lower Jurassic of Europe, but its
      presence has not previously been confirmed in younger (Middle Jurassic) rocks
      from the northern hemisphere. CONCLUSIONS/SIGNIFICANCE: This specimen represents
      the only diagnostic ichthyosaur remains reported from the Aalenian. It bears
      numerous similarities in size and in morphology to the Lower Jurassic species of
      the genus Stenopterygius and provides additional evidence that the major
      ecological changes hypothesized to have occurred at the end of the Toarcian took
      place sometime after this point and most likely did not occur suddenly. There is
      currently no evidence for the presence of ophthalmosaurids in the northern
      hemisphere during the Aalenian-Bathonian interval.

PMID- 22870245
TI  - Exercise training prevents oxidative stress and ubiquitin-proteasome system
      overactivity and reverse skeletal muscle atrophy in heart failure.
AB  - BACKGROUND: Heart failure (HF) is known to lead to skeletal muscle atrophy and
      dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are
      not fully understood. We hypothesized that HF would increase oxidative stress and
      ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic
      hyperactivity mouse model. We also tested the hypothesis that aerobic exercise
      training (AET) would reestablish UPS activation in mice and human HF.
      METHODS/PRINCIPAL FINDINGS: Time-course evaluation of plantaris muscle cross
      sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin
      like proteasome activity was performed in a mouse model of sympathetic
      hyperactivity-induced HF. At the 7(th) month of age, HF mice displayed skeletal
      muscle atrophy, increased oxidative stress and UPS overactivation. Moderate
      intensity AET restored lipid hydroperoxides and carbonylated protein levels
      paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like
      proteasome activity and plantaris trophicity. In human HF (patients randomized to
      sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like
      proteasome activity was also increased and AET restored it to healthy control
      subjects' levels. CONCLUSIONS: Collectively, our data provide evidence that AET
      effectively counteracts redox imbalance and UPS overactivation, preventing
      skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced
      HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome
      activity paralleled by improved aerobic capacity in HF patients, which is not
      achieved by drug treatment itself. Altogether these findings strengthen the
      clinical relevance of AET in the treatment of HF.

PMID- 22870246
TI  - Does pet arrival trigger prosocial behaviors in individuals with autism?
AB  - Alteration of social interactions especially prosocial behaviors--an important
      aspect of development--is one of the characteristics of autistic disorders.
      Numerous strategies or therapies are used to improve communication skills or at
      least to reduce social impairments. Animal-assisted therapies are used widely but
      their relevant benefits have never been scientifically evaluated. In the present
      study, we evaluated the association between the presence or the arrival of pets
      in families with an individual with autism and the changes in his or her
      prosocial behaviors. Of 260 individuals with autism--on the basis of presence or
      absence of pets--two groups of 12 individuals and two groups of 8 individuals
      were assigned to: study 1 (pet arrival after age of 5 versus no pet) and study 2
      (pet versus no pet), respectively. Evaluation of social impairment was assessed
      at two time periods using the 36-items ADI-R algorithm and a parental
      questionnaire about their child-pet relationships. The results showed that 2 of
      the 36 items changed positively between the age of 4 to 5 (t(0)) and time of
      assessment (t(1)) in the pet arrival group (study 1): "offering to share" and
      "offering comfort". Interestingly, these two items reflect prosocial behaviors.
      There seemed to be no significant changes in any item for the three other groups.
      The interactions between individuals with autism and their pets were more-
      qualitatively and quantitatively--reported in the situation of pet arrival than
      pet presence since birth. These findings open further lines of research on the
      impact of pet's presence or arrival in families with an individual with autism.
      Given the potential ability of individuals with autism to develop prosocial
      behaviors, related studies are needed to better understand the mechanisms
      involved in the development of such child-pet relationship.

PMID- 22870247
TI  - Increased JNK1 signaling pathway is responsible for ABCG2-mediated multidrug
      resistance in human colon cancer.
AB  - Multidrug resistance remains a major obstacle to effective chemotherapy of colon
      cancer. ABCG2, as a half-transporter of the G subfamily of ATP-binding cassette
      transporter genes (ABC transporters), is known to play a crucial role in
      multidrug resistance. However, the molecular mechanism of controlling ABCG2
      expression in drug resistance of colon cancer is unclear and scarcely reported.
      In the present study, we systematically investigate the potential role of the c
      Jun NH2-terminal kinase (JNK) signal pathway in ABCG2-induced multidrug
      resistance in colon cancer. In the hydroxycamptothecin (HCPT) resistant cell line
      SW1116/HCPT from human colon cancer cell line SW1116, ABCG2 is the major factor
      for multidrug resistance, other than well-studied ABCB1 or ABCC1. Our findings
      indicate that blocking the JNK pathway by pathway inhibitor SP600125 reduces the
      expression level and transport function of ABCG2 in drug-resistant cells
      SW116/HCPT. Notably, the experiments of small interfering RNA directed against
      JNK1 and JNK2 show that only silence of JNK1 gene has the equal effect as
      SP600125 on dephosphorylation of transcription factor c-Jun and the expression of
      ABCG2 protein, while the corresponding phenomena were not observed after silence
      of JNK2 gene. Meanwhile, SP600125 induces the apoptosis of SW116/HCPT cells by
      promoting the cleavage of PARP and suppressing the anti-apoptotic protein
      survivin and bcl-2, and increases the sensitivity of SW1116/HCPT to HCPT. Taken
      together, our work demonstrated that JNK1/c-jun signaling pathway was involved in
      ABCG2-mediated multidrug resistance in colon cancer cells. Definitely, inhibition
      of the JNK1/c-jun pathway is useful for reversing ABCG2-mediated drug resistance
      in HCPT-resistant colon cancer cells.

PMID- 22870248
TI  - An assessment of the screening method to evaluate vaccine effectiveness: the case
      of 7-valent pneumococcal conjugate vaccine in the United States.
AB  - The screening method, which employs readily available data, is an inexpensive and
      quick means of estimating vaccine effectiveness (VE). We compared estimates of
      effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against
      invasive pneumococcal disease (IPD) using the screening and case-control methods.
      Cases were children aged 19-35 months with pneumococcus isolated from normally
      sterile sites residing in Active Bacterial Core surveillance areas in the United
      States. Case-control VE was estimated for 2001-2004 by comparing the odds of
      vaccination among cases and community controls. Screening-method VE for 2001-2009
      was estimated by comparing the proportion of cases vaccinated to National
      Immunization Survey-derived coverage among the general population. To evaluate
      the plausibility of screening-method VE findings, we estimated attack rates among
      vaccinated and unvaccinated persons. We identified 1,154 children with IPD.
      Annual population PCV7 coverage with >=1 dose increased from 38% to 97%. Case
      control VE for >=1 dose was estimated as 75% against all-serotype IPD (annual
      range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the
      screening method, the overall VE was 86% for >=1 dose (annual range: -240-70%)
      against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As
      cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all
      serotype IPD among vaccinated and unvaccinated individuals became less consistent
      than what would be expected with the estimated effectiveness of PCV7. The
      screening method yields estimates of VE that are highly dependent on the time
      period during which it is used and the choice of outcome. The method should be
      used cautiously to evaluate VE of PCVs.

PMID- 22870249
TI  - Making co-enrolment feasible for randomised controlled trials in paediatric
      intensive care.
AB  - AIMS: Enrolling children into several trials could increase recruitment and lead
      to quicker delivery of optimal care in paediatric intensive care units (PICU). We
      evaluated decisions taken by clinicians and parents in PICU on co-enrolment for
      two large pragmatic trials: the CATCH trial (CATheters in CHildren) comparing
      impregnated with standard central venous catheters (CVCs) for reducing
      bloodstream infection in PICU and the CHIP trial comparing tight versus standard
      control of hyperglycaemia. METHODS: We recorded the period of trial overlap for
      all PICUs taking part in both CATCH and CHiP and reasons why clinicians decided
      to co-enrol children or not into both studies. We examined parental decisions on
      co-enrolment by measuring recruitment rates and reasons for declining consent.
      RESULTS: Five PICUs recruited for CATCH and CHiP during the same period (an
      additional four opened CATCH after having closed CHiP). Of these five, three
      declined co-enrolment (one of which delayed recruiting elective patients for
      CATCH whilst CHiP was running), due to concerns about jeopardising CHiP
      recruitment, asking too much of parents, overwhelming amounts of information to
      explain to parents for two trials and a policy against co-enrolment. Two units co
      enrolled in order to maximise recruitment to both trials. At the first unit, 35
      parents were approached for both trials. 17/35 consented to both; 13/35 consented
      to one trial only; 5/35 declined both. Consent rates during co-enrolment were
      29/35 (82%) and 18/35 (51%) for CATCH and CHiP respectively compared with 78% and
      51% respectively for those approached for a single trial within this PICU. The
      second unit did not record data on approaches or refusals, but successfully co
      enrolled one child. CONCLUSIONS: Co-enrolment did not appear to jeopardise
      recruitment or overwhelm parents. Strategies for seeking consent for multiple
      trials need to be developed and should include how to combine information for
      parents and patients.

PMID- 22870250
TI  - Motor deficits in schizophrenia quantified by nonlinear analysis of postural
      sway.
AB  - Motor dysfunction is a consistently reported but understudied aspect of
      schizophrenia. Postural sway area was examined in individuals with schizophrenia
      under four conditions with different amounts of visual and proprioceptive
      feedback: eyes open or closed and feet together or shoulder width apart. The
      nonlinear complexity of postural sway was assessed by detrended fluctuation
      analysis (DFA). The schizophrenia group (n = 27) exhibited greater sway area
      compared to controls (n = 37). Participants with schizophrenia showed increased
      sway area following the removal of visual input, while this pattern was absent in
      controls. Examination of DFA revealed decreased complexity of postural sway and
      abnormal changes in complexity upon removal of visual input in individuals with
      schizophrenia. Additionally, less complex postural sway was associated with
      increased symptom severity in participants with schizophrenia. Given the critical
      involvement of the cerebellum and related circuits in postural stability and
      sensorimotor integration, these results are consistent with growing evidence of
      motor, cerebellar, and sensory integration dysfunction in the disorder, and with
      theoretical models that implicate cerebellar deficits and more general
      disconnection of function in schizophrenia.

PMID- 22870251
TI  - Voice and handgrip strength predict reproductive success in a group of indigenous
      African females.
AB  - Evolutionary accounts of human traits are often based on proxies for genetic
      fitness (e.g., number of sex partners, facial attractiveness). Instead of using
      proxies, actual differences in reproductive success is a more direct measure of
      darwinian fitness. Certain voice acoustics such as fundamental frequency and
      measures of health such as handgrip strength correlate with proxies of fitness,
      yet there are few studies showing the relation of these traits to reproduction.
      Here, we explore whether the fundamental frequency of the voice and handgrip
      strength account for differences in actual reproduction among a population of
      natural fertility humans. Our results show that both fundamental frequency and
      handgrip strength predict several measures of reproductive success among a group
      of indigenous Namibian females, particularly amongst the elderly, with weight
      also predicting reproductive outcomes among males. These findings demonstrate
      that both hormonally regulated and phenotypic quality markers can be used as
      measures of darwinian fitness among humans living under conditions that resemble
      the evolutionary environment of Homo sapiens. We also argue that these findings
      provide support for the Grandmother Hypothesis.

PMID- 22870252
TI  - NEXCADE: perturbation analysis for complex networks.
AB  - Recent advances in network theory have led to considerable progress in our
      understanding of complex real world systems and their behavior in response to
      external threats or fluctuations. Much of this research has been invigorated by
      demonstration of the 'robust, yet fragile' nature of cellular and large-scale
      systems transcending biology, sociology, and ecology, through application of the
      network theory to diverse interactions observed in nature such as plant
      pollinator, seed-dispersal agent and host-parasite relationships. In this work,
      we report the development of NEXCADE, an automated and interactive program for
      inducing disturbances into complex systems defined by networks, focusing on the
      changes in global network topology and connectivity as a function of the
      perturbation. NEXCADE uses a graph theoretical approach to simulate perturbations
      in a user-defined manner, singly, in clusters, or sequentially. To demonstrate
      the promise it holds for broader adoption by the research community, we provide
      pre-simulated examples from diverse real-world networks including eukaryotic
      protein-protein interaction networks, fungal biochemical networks, a variety of
      ecological food webs in nature as well as social networks. NEXCADE not only
      enables network visualization at every step of the targeted attacks, but also
      allows risk assessment, i.e. identification of nodes critical for the robustness
      of the system of interest, in order to devise and implement context-based
      strategies for restructuring a network, or to achieve resilience against link or
      node failures. Source code and license for the software, designed to work on a
      Linux-based operating system (OS) can be downloaded at
      http://www.nipgr.res.in/nexcade_download.html. In addition, we have developed
      NEXCADE as an OS-independent online web server freely available to the scientific
      community without any login requirement at http://www.nipgr.res.in/nexcade.html.

PMID- 22870253
TI  - Carbon monoxide improves cardiac function and mitochondrial population quality in
      a mouse model of metabolic syndrome.
AB  - AIMS: Metabolic syndrome induces cardiac dysfunction associated with mitochondria
      abnormalities. As low levels of carbon monoxide (CO) may improve myocardial and
      mitochondrial activities, we tested whether a CO-releasing molecule (CORM-3)
      reverses metabolic syndrome-induced cardiac alteration through changes in
      mitochondrial biogenesis, dynamics and autophagy. METHODS AND RESULTS: Mice were
      fed with normal diet (ND) or high-fat diet (HFD) for twelve weeks. Then, mice
      received two intraperitoneal injections of CORM-3 (10 mg x kg(-1)), with the
      second one given 16 hours after the first. Contractile function in isolated
      hearts and mitochondrial parameters were evaluated 24 hours after the last
      injection. Mitochondrial population was explored by electron microscopy. Changes
      in mitochondrial dynamics, biogenesis and autophagy were assessed by western-blot
      and RT-qPCR. Left ventricular developed pressure was reduced in HFD hearts.
      Mitochondria from HFD hearts presented reduced membrane potential and diminished
      ADP-coupled respiration. CORM-3 restored both cardiac and mitochondrial
      functions. Size and number of mitochondria increased in the HFD hearts but not in
      the CORM-3-treated HFD group. CORM-3 modulated HFD-activated mitochondrial fusion
      and biogenesis signalling. While autophagy was not activated in the HFD group,
      CORM-3 increased the autophagy marker LC3-II. Finally, ex vivo experiments
      demonstrated that autophagy inhibition by 3-methyladenine abolished the
      cardioprotective effects of CORM-3. CONCLUSION: CORM-3 may modulate pathways
      controlling mitochondrial quality, thus leading to improvements of mitochondrial
      efficiency and HFD-induced cardiac dysfunction.

PMID- 22870254
TI  - Resistance to BmNPV via overexpression of an exogenous gene controlled by an
      inducible promoter and enhancer in transgenic silkworm, Bombyx mori.
AB  - The hycu-ep32 gene of Hyphantria cunea NPV can inhibit Bombyx mori
      nucleopolyhedrovirus (BmNPV) multiplication in co-infected cells, but it is not
      known whether the overexpression of the hycu-ep32 gene has an antiviral effect in
      the silkworm, Bombyx mori. Thus, we constructed four transgenic vectors, which
      were under the control of the 39 K promoter of BmNPV (39 KP), Bombyx mori A4
      promoter (A4P), hr3 enhancer of BmNPV combined with 39 KP, and hr3 combined with
      A4P. Transgenic lines were created via embryo microinjection using practical
      diapause silkworm. qPCR revealed that the expression level of hycu-ep32 could be
      induced effectively after BmNPV infection in transgenic lines where hycu-ep32 was
      controlled by hr3 combined with 39 KP (i.e., HEKG). After oral inoculation of
      BmNPV with 3 * 10(5) occlusion bodies per third instar, the mortality with HEKG-B
      was approximately 30% lower compared with the non-transgenic line. The economic
      characteristics of the transgenic lines remained unchanged. These results suggest
      that overexpression of an exogenous antiviral gene controlled by an inducible
      promoter and enhancer is a feasible method for breeding silkworms with a high
      antiviral capacity.

PMID- 22870255
TI  - Aphid alarm pheromone as a cue for ants to locate aphid partners.
AB  - The mutualistic relationships that occur between myrmecophilous aphids and ants
      are based on the rich food supply that honeydew represents for ants and on the
      protection they provide against aphid natural enemies. While aphid predators and
      parasitoids actively forage for oviposition sites by using aphid semiochemicals,
      scouts of aphid-tending ant species would also benefit from locating honeydew
      resources by orienting toward aphid pheromone sources. The present study aims to
      provide additional information on the use of Aphis fabae alarm pheromone, i.e.
      (E)-beta-farnesene (EbetaF), by ant scouts. The perception and behavioral impact
      of EbetaF on Lasius niger were investigated using electroantennography and two
      bio-assays measuring their attraction and orientation towards aphid
      semiochemicals. Pronounced electrical depolarizations were observed from L. niger
      scout antennae to stimulations of A. fabae alarm pheromone, while other
      sesquiterpenes elicited weak or no responses. L. niger scouts were significantly
      attracted toward EbetaF in a four-arm olfactometer, as well as in an two-choice
      bioassay. These laboratory results suggest for the first time that low amounts of
      aphid alarm pheromone can be used by L. niger scouts as a cue indicating the
      presence of aphid colonies and could therefore mediate the aphid-ant partnership
      in the field.

PMID- 22870256
TI  - Hormonal induction of polo-like kinases (Plks) and impact of Plk2 on cell cycle
      progression in the rat ovary.
AB  - The highly conserved polo-like kinases (Plks) are potent regulators of multiple
      functions in the cell cycle before and during mitotic cell division. We
      investigated the expression pattern of Plk genes and their potential role(s) in
      the rat ovary during the periovulatory period. Plk2 and Plk3 were highly induced
      both in intact ovaries and granulosa cells in vivo after treatment with the
      luteinizing hormone (LH) agonist, human chorionic gonadotropin (hCG). In vitro,
      hCG stimulated the expression of Plk2 in granulosa cells, but not Plk3. This
      induction of Plk2 expression was mimicked by both forskolin and phorbol 12
      myristate 13-acetate (PMA). Moreover, Plk2 expression was reduced by inhibitors
      of prostaglandin synthesis or the EGF pathway, but not by progesterone receptor
      antagonist (RU486) treatment. At the promoter level, mutation of the Sp1 binding
      sequence abolished the transcriptional activity of the Plk2 gene. ChIP assays
      also revealed the interaction of endogenous Sp1 protein in the Plk2 promoter
      region. Functionally, the over-expression of Plk2 and Plk3 arrested granulosa
      cells at the G0/G1 phase of the cell cycle. In contrast, the knockdown of Plk2
      expression in granulosa cells decreased the number of cells in the G0/G1 stage of
      the cell cycle, but increased granulosa cell viability. In summary, hCG induced
      Plk2 and Plk3 expression in the rat ovary. Prostaglandins and the EGF signaling
      pathway are involved in regulating Plk2 expression. The transcription factor Sp1
      is important for Plk2 transcriptional up-regulation. Our findings suggest that
      the increase in Plk2 and Plk3 expression contributes to the cell cycle arrest of
      granulosa cells which is important for the luteinization of granulosa cells
      during the periovulatory period.

PMID- 22870257
TI  - The pattern of genetic variability in apomictic clones of Taraxacum officinale
      indicates the alternation of asexual and sexual histories of apomicts.
AB  - Dandelions (genus Taraxacum) comprise a group of sexual diploids and apomictic
      polyploids with a complicated reticular evolution. Apomixis (clonal reproduction
      through seeds) in this genus is considered to be obligate, and therefore
      represent a good model for studying the role of asexual reproduction in
      microevolutionary processes of apomictic genera. In our study, a total of 187
      apomictic individuals composing a set of nine microspecies (sampled across wide
      geographic area in Europe) were genotyped for six microsatellite loci and for 162
      amplified fragment length polymorphism (AFLP) markers. Our results indicated that
      significant genetic similarity existed within accessions with low numbers of
      genotypes. Genotypic variability was high among accessions but low within
      accessions. Clustering methods discriminated individuals into nine groups
      corresponding to their phenotypes. Furthermore, two groups of apomictic genotypes
      were observed, which suggests that they had different asexual histories. A matrix
      compatibility test suggests that most of the variability within accession groups
      was mutational in origin. However, the presence of recombination was also
      detected. The accumulation of mutations in asexual clones leads to the
      establishment of a network of clone mates. However, this study suggests that the
      clones primarily originated from the hybridisation between sexual and apomicts.

PMID- 22870258
TI  - The relationships between body composition and the systemic inflammatory response
      in patients with primary operable colorectal cancer.
AB  - BACKGROUND: Weight loss is recognised as a marker of poor prognosis in patients
      with cancer but the aetiology of cancer cachexia remains unclear. The aim of the
      present study was to examine the relationships between CT measured parameters of
      body composition and the systemic inflammatory response in patients with primary
      operable colorectal cancer. PATIENT AND METHODS: 174 patients with primary
      operable colorectal cancer who underwent resection with curative intent (2003
      2010). Image analysis of CT scans was used to measure total fat index
      (cm(2)/m(2)), subcutaneous fat index (cm(2)/m(2)), visceral fat index
      (cm(2)/m(2)) and skeletal muscle index (cm(2)/m(2)). Systemic inflammatory
      response was measured by serum white cell count (WCC), neutrophil:lymphocyte
      ratio (NLR) and the Glasgow Prognostic Score (mGPS). RESULTS: There were no
      relationships between any parameter of body composition and serum WCC or NLR.
      There was a significant relationship between low skeletal muscle index and an
      elevated systemic inflammatory response, as measured by the mGPS (p = 0.001).
      This was confirmed by linear relationships between skeletal muscle index and both
      C-reactive protein (r = -0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There
      was no association between skeletal muscle index and tumour stage. CONCLUSIONS:
      The present study highlights a direct relationship between low levels of skeletal
      muscle and the presence of a systemic inflammatory response in patients with
      primary operable colorectal cancer.

PMID- 22870259
TI  - Gametogenesis and auxospore development in Actinocyclus (Bacillariophyta).
AB  - cGametogenesis and auxospore development have been studied in detail in
      surprisingly few centric diatoms. We studied the development of sperm, eggs and
      auxospores in Actinocyclus sp., a radially symmetrical freshwater diatom
      collected from Japan, using LM and electron microscopy of living cultures and
      thin sections. Actinocyclus represents a deep branch of the 'radial centric'
      diatoms and should therefore contribute useful insights into the evolution of
      sexual reproduction in diatoms. Spermatogenesis was examined by LM and SEM and
      involved the formation of two spermatogonia (sperm mother-cells) in each
      spermatogonangium through an equal mitotic division. The spermatogonia produced a
      reduced 'lid' valve, resembling a large flat scale with irregular radial
      thickenings. Sperm formation was merogenous, producing four sperm per
      spermatogonium, which were released by dehiscence of the 'lid' valve. The sperm
      were spindle-shaped with numerous surface globules and, as usual for diatoms, the
      single anterior flagellum bore mastigonemes. One egg cell was produced per
      oogonium. Immature eggs produced a thin layer of circular silica scales before
      fertilization, while the eggs were still contained within the oogonium. Sperm
      were attracted in large numbers to each egg and were apparently able to contact
      the egg surface via a gap formed between the long hypotheca and shorter epitheca
      of the oogonium and a small underlying hole in the scale-case. Auxospores
      expanded isodiametrically and many new scales were added to its envelope during
      expansion. Finally, new slightly-domed initial valves were produced at right
      angles to the oogonium axis, after a strong contraction of the cell away from the
      auxospore wall. At different stages, Golgi bodies were associated with
      chloroplasts or mitochondria, contrasting with the constancy of Golgi-ER
      mitochondrion (G-ER-M) units in some other centric diatoms, which has been
      suggested to have phylogenetic significance. Electron-dense bodies in the vacuole
      of Actinocyclus are probably acidocalcisomes containing polyphosphate.

PMID- 22870260
TI  - Adolescent expectations of early death predict adult risk behaviors.
AB  - Only a handful of public health studies have investigated expectations of early
      death among adolescents. Associations have been found between these expectations
      and risk behaviors in adolescence. However, these beliefs may not only predict
      worse adolescent outcomes, but worse trajectories in health with ties to negative
      outcomes that endure into young adulthood. The objectives of this study were to
      investigate perceived chances of living to age 35 (Perceived Survival
      Expectations, PSE) as a predictor of suicidal ideation, suicide attempt and
      substance use in young adulthood. We examined the predictive capacity of PSE on
      future suicidal ideation/attempt after accounting for sociodemographics,
      depressive symptoms, and history of suicide among family and friends to more
      fully assess its unique contribution to suicide risk. We investigated the
      influence of PSE on legal and illegal substance use and varying levels of
      substance use. We utilized the National Longitudinal Study of Adolescent Health
      (Add Health) initiated in 1994-95 among 20,745 adolescents in grades 7-12 with
      follow-up interviews in 1996 (Wave II), 2001-02 (Wave III) and 2008 (Wave IV;
      ages 24-32). Compared to those who were almost certain of living to age 35,
      perceiving a 50-50 or less chance of living to age 35 at Waves I or III predicted
      suicide attempt and ideation as well as regular substance use (i.e., exceeding
      daily limits for moderate drinking; smoking >= a pack/day; and using illicit
      substances other than marijuana at least weekly) at Wave IV. Associations between
      PSE and detrimental adult outcomes were particularly strong for those reporting
      persistently low PSE at both Waves I and III. Low PSE at Wave I or Wave III was
      also related to a doubling and tripling, respectively, of death rates in young
      adulthood. Long-term and wide-ranging ties between PSE and detrimental outcomes
      suggest these expectations may contribute to identifying at-risk youth.

PMID- 22870261
TI  - Social network analysis in healthcare settings: a systematic scoping review.
AB  - BACKGROUND: Social network analysis (SNA) has been widely used across a range of
      disciplines but is most commonly applied to help improve the effectiveness and
      efficiency of decision making processes in commercial organisations. We are
      utilising SNA to inform the development and implementation of tailored behaviour
      change interventions to improve the uptake of evidence into practice in the
      English National Health Service. To inform this work, we conducted a systematic
      scoping review to identify and evaluate the use of SNA as part of an intervention
      to support the implementation of change in healthcare settings. METHODS AND
      FINDINGS: We searched ten bibliographic databases to October 2011. We also
      searched reference lists, hand searched selected journals and websites, and
      contacted experts in the field. To be eligible for the review, studies had to
      describe and report the results of an SNA performed with healthcare professionals
      (e.g. doctors, nurses, pharmacists, radiographers etc.) and others involved in
      their professional social networks. We included 52 completed studies, reported in
      62 publications. Almost all of the studies were limited to cross sectional
      descriptions of networks; only one involved using the results of the SNA as part
      of an intervention to change practice. CONCLUSIONS: We found very little evidence
      for the potential of SNA being realised in healthcare settings. However, it seems
      unlikely that networks are less important in healthcare than other settings.
      Future research should seek to go beyond the merely descriptive to implement and
      evaluate SNA-based interventions.

PMID- 22870262
TI  - Were equatorial regions less affected by the 2009 influenza pandemic? The
      Brazilian experience.
AB  - Although it is in the Tropics where nearly half of the world population lives and
      infectious disease burden is highest, little is known about the impact of
      influenza pandemics in this area. We investigated the mortality impact of the
      2009 influenza pandemic relative to mortality rates from various outcomes in pre
      pandemic years throughout a wide range of latitudes encompassing the entire
      tropical, and part of the subtropical, zone of the Southern Hemisphere (+5(
      degrees )N to -35( degrees )S) by focusing on a country with relatively uniform
      health care, disease surveillance, immunization and mitigation policies: Brazil.
      To this end, we analyzed laboratory-confirmed deaths and vital statistics
      mortality beyond pre-pandemic levels for each Brazilian state. Pneumonia,
      influenza and respiratory mortality were significantly higher during the
      pandemic, affecting predominantly adults aged 25 to 65 years. Overall, there were
      2,273 and 2,787 additional P&I- and respiratory deaths during the pandemic,
      corresponding to a 5.2% and 2.7% increase, respectively, over average pre
      pandemic annual mortality. However, there was a marked spatial structure in
      mortality that was independent of socio-demographic indicators and inversely
      related with income: mortality was progressively lower towards equatorial
      regions, where low or no difference from pre-pandemic mortality levels was
      identified. Additionally, the onset of pandemic-associated mortality was
      progressively delayed in equatorial states. Unexpectedly, there was no additional
      mortality from circulatory causes. Comparing disease burden reliably across
      regions is critical in those areas marked by competing health priorities and
      limited resources. Our results suggest, however, that tropical regions of the
      Southern Hemisphere may have been disproportionally less affected by the
      pandemic, and that climate may have played a key role in this regard. These
      findings have a direct bearing on global estimates of pandemic burden and the
      assessment of the role of immunological, socioeconomic and environmental drivers
      of the transmissibility and severity of this pandemic.

PMID- 22870263
TI  - Modulating uranium binding affinity in engineered calmodulin EF-hand peptides:
      effect of phosphorylation.
AB  - To improve our understanding of uranium toxicity, the determinants of uranyl
      affinity in proteins must be better characterized. In this work, we analyzed the
      contribution of a phosphoryl group on uranium binding affinity in a protein
      binding site, using the site 1 EF-hand motif of calmodulin. The recombinant
      domain 1 of calmodulin from A. thaliana was engineered to impair metal binding at
      site 2 and was used as a structured template. Threonine at position 9 of the loop
      was phosphorylated in vitro, using the recombinant catalytic subunit of protein
      kinase CK2. Hence, the T(9)TKE(12) sequence was substituted by the CK2
      recognition sequence TAAE. A tyrosine was introduced at position 7, so that
      uranyl and calcium binding affinities could be determined by following tyrosine
      fluorescence. Phosphorylation was characterized by ESI-MS spectrometry, and the
      phosphorylated peptide was purified to homogeneity using ion-exchange
      chromatography. The binding constants for uranyl were determined by competition
      experiments with iminodiacetate. At pH 6, phosphorylation increased the affinity
      for uranyl by a factor of ~5, from K(d) = 25+/-6 nM to K(d) = 5+/-1 nM. The
      phosphorylated peptide exhibited a much larger affinity at pH 7, with a
      dissociation constant in the subnanomolar range (K(d) = 0.25+/-0.06 nM). FTIR
      analyses showed that the phosphothreonine side chain is partly protonated at pH
      6, while it is fully deprotonated at pH 7. Moreover, formation of the uranyl
      peptide complex at pH 7 resulted in significant frequency shifts of the nu(as)(P
      O) and nu(s)(P-O) IR modes of phosphothreonine, supporting its direct interaction
      with uranyl. Accordingly, a bathochromic shift in nu(as)(UO(2))(2+) vibration
      (from 923 cm(-1) to 908 cm(-1)) was observed upon uranyl coordination to the
      phosphorylated peptide. Together, our data demonstrate that the phosphoryl group
      plays a determining role in uranyl binding affinity to proteins at physiological
      pH.

PMID- 22870264
TI  - Differences in the inflammatory response induced by acute pancreatitis in
      different white adipose tissue sites in the rat.
AB  - BACKGROUND: There is increasing evidence of the role of adipose tissue on the
      systemic effects of acute pancreatitis. Patients with higher body mass index have
      increased risk of local and systemic complications and patients with android fat
      distribution and higher waist circumference are at greater risk for developing
      the severe form of the disease. Here we evaluated the changes on different areas
      of adipose tissue and its involvement on the inflammatory response in an
      experimental model of acute pancreatitis. METHODS: Pancreatitis was induced in
      male Wistar rats by intraductal administration of sodium taurocholate. Orlistat
      was administered to inhibit lipase activity. Activation of peritoneal macrophages
      was evaluated by measuring IL1beta and TNFalpha expression. Inflammation was
      evaluated by measuring myeloperoxidase activity in mesenteric, epididymal and
      retroperitoneal areas of adipose tissue. Changes in the expression of
      inflammatory mediator in these areas of adipose tissue were also evaluated by RT
      PCR. RESULTS: Pancreatitis induces the activation of peritoneal macrophages and a
      strong inflammatory response in mesenteric and epididymal sites of adipose
      tissue. By contrast, no changes were found in retroperitoneal adipose tissue.
      Inhibition of lipase prevented the activation of macrophages and the local
      inflammation in adipose tissue. CONCLUSIONS: Our results confirm the involvement
      of adipose tissue on the progression of systemic inflammatory response during
      acute pancreatitis. However, there is a considerable diversity in different
      adipose tissue sites. These differences need to be taken into account in order to
      understand the progression from local pancreatic damage to systemic inflammation
      during acute pancreatitis.

PMID- 22870265
TI  - A phase I double blind, placebo-controlled, randomized study of a multigenic HIV
      1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.
AB  - BACKGROUND: We conducted a phase I, randomized, double-blind, placebo-controlled
      trial to assess the safety and immunogenicity of escalating doses of two
      recombinant replication defective adenovirus serotype 35 (Ad35) vectors
      containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env
      (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56
      healthy HIV-uninfected adults. METHODS: Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV
      mixed in the same vial in equal proportions) or Ad35-GRIN was administered
      intramuscularly at 0 and 6 months. Participants were randomized to receive either
      vaccine or placebo (10/4 per group, respectively) within one of four dosage
      groups: Ad35-GRIN/ENV 2*10(9) (A), 2*10(10) (B), 2*10(11) (C), or Ad35-GRIN
      1*10(10) (D) viral particles. RESULTS: No vaccine-related serious adverse event
      was reported. Reactogenicity events reported were dose-dependent, mostly mild or
      moderate, some severe in Group C volunteers, all transient and resolving
      spontaneously. IFN-gamma ELISPOT responses to any vaccine antigen were detected
      in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of
      Groups A-D vaccine recipients after the second vaccination, respectively. The
      median spot forming cells (SFC) per 10(6) PBMC to any antigen was 78-139 across
      Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum
      of 2991 SFC. Four to five HIV proteins were commonly recognized across all the
      groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were
      polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag
      antibodies in most vaccinees after the second immunization. Ad35 neutralizing
      titers remained low after the second vaccination. CONCLUSION/SIGNIFICANCE: Ad35
      GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral
      responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or
      Ad35-GRIN and increased after the second vaccination. T-cell responses were broad
      and polyfunctional. TRIAL REGISTRATION: ClinicalTrials.gov NCT00851383.

PMID- 22870266
TI  - Therapeutic intervention for chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS): a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been
      treated with several different interventions with limited success. This meta
      analysis aims to review all trials reporting on therapeutic intervention for
      CP/CPPS using the National Institutes of Health-Chronic Prostatitis Symptom Index
      (NIH-CPSI). METHODS: We searched Medline, PubMed, the Cochrane Pain, Palliative &
      Supportive Care Trials, the Cochrane Register of Controlled Trials, CINAHL,
      ClinicalTrials.gov, and the NIDDK website between 1947 and December 31, 2011
      without language or study type restrictions. All RCTs for CP/CPPS lasting at
      least 6 weeks, with a minimum of 10 participants per arm, and using the NIH-CPSI
      score, the criterion standard for CP/CPPS, as an outcome measure were included.
      Data was extracted from each study by two independent reviewers. Gillbraith and I
      squared plots were used for heterogeneity testing and Eggers and Peters methods
      for publication bias. Quality was assessed using a component approach and meta
      regression was used to analyze sources of heterogeneity. RESULTS: Mepartricin,
      percutaneous tibial nerve stimulation (PTNS), and triple therapy comprised of
      doxazosin + ibuprofen + thiocolchicoside (DIT) resulted in clinically and
      statistically significant reduction in NIH-CPSI total score. The same agents and
      aerobic exercise resulted in clinically and statistically significant NIH-CPSI
      pain domain score reduction. Acupuncture, DIT, and PTNS were found to produce
      statistically and clinically significant reductions in the NIH-CPSI voiding
      domain. A statistically significant placebo effect was found for all outcomes and
      time analysis showed that efficacy of all treatments increased over time. Alpha
      blockers, antibiotics, and combinations of the two failed to show statistically
      or clinically significant NIH-CPSI reductions. CONCLUSION: Results from this meta
      analysis reflect our current inability to effectively manage CP/CPPS. Clinicians
      and researchers must consider placebo effect and treatment efficacy over time and
      design studies creatively so we can more fully elucidate the etiology and role of
      therapeutic intervention in CP/CPPS.

PMID- 22870267
TI  - SIMPLEX: cloud-enabled pipeline for the comprehensive analysis of exome
      sequencing data.
AB  - In recent studies, exome sequencing has proven to be a successful screening tool
      for the identification of candidate genes causing rare genetic diseases. Although
      underlying targeted sequencing methods are well established, necessary data
      handling and focused, structured analysis still remain demanding tasks. Here, we
      present a cloud-enabled autonomous analysis pipeline, which comprises the
      complete exome analysis workflow. The pipeline combines several in-house
      developed and published applications to perform the following steps: (a) initial
      quality control, (b) intelligent data filtering and pre-processing, (c) sequence
      alignment to a reference genome, (d) SNP and DIP detection, (e) functional
      annotation of variants using different approaches, and (f) detailed report
      generation during various stages of the workflow. The pipeline connects the
      selected analysis steps, exposes all available parameters for customized usage,
      performs required data handling, and distributes computationally expensive tasks
      either on a dedicated high-performance computing infrastructure or on the Amazon
      cloud environment (EC2). The presented application has already been used in
      several research projects including studies to elucidate the role of rare genetic
      diseases. The pipeline is continuously tested and is publicly available under the
      GPL as a VirtualBox or Cloud image at http://simplex.i-med.ac.at; additional
      supplementary data is provided at http://www.icbi.at/exome.

PMID- 22870268
TI  - Differential effects of cystathionine-gamma-lyase-dependent vasodilatory H2S in
      periadventitial vasoregulation of rat and mouse aortas.
AB  - BACKGROUND: Hydrogen sulfide (H(2)S) is a potent vasodilator. However, the
      complex mechanisms of vasoregulation by H(2)S are not fully understood. We tested
      the hypotheses that (1) H(2)S exerts vasodilatory effects by opening KCNQ-type
      voltage-dependent (K(v)) K(+) channels and (2) that H(2)S-producing cystathionine
      gamma-lyase (CSE) in perivascular adipose tissue plays a major role in this
      pathway. METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas
      was used. NaHS and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) were used
      as H(2)S donors. KCNQ-type K(v) channels were blocked by XE991. 4
      Propargylglycine (PPG) and beta-cyano-l-alanine (BCA), or 2-(aminooxy)-acetic
      acid (AOAA) were used as inhibitors of CSE or cystathionine-beta-synthase (CBS),
      respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse
      aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular
      adipose tissue (PVAT) exerted an anticontractile effect in these arteries. CSE
      inhibition by PPG and BCA reduced this effect in aortas from rats but not from
      mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of
      PVAT. XE991, however, almost completely suppressed the anticontractile effects of
      PVAT in both species. Exogenous l-cysteine, substrate for the endogenous
      production of H(2)S, induced vasorelaxation only at concentrations >5 mmol/l, an
      effect unchanged by CSE inhibition. CONCLUSIONS/SIGNFICANCE: Our results
      demonstrate potent vasorelaxant effects of H(2)S donors in large arteries of both
      rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal
      role. CSE-H(2)S seems to modulate the effect of adipocyte-derived relaxing factor
      in rat but not in mouse aorta. The present study provides novel insight into the
      interaction of CSE-H(2)S and perivascular adipose tissue. Furthermore, with
      additional technical advances, a future clinical approach targeting vascular
      H(2)S/KCNQ pathways to influence states of vascular dysfunction may be possible.

PMID- 22870269
TI  - Progression of mouse skin carcinogenesis is associated with increased ERalpha
      levels and is repressed by a dominant negative form of ERalpha.
AB  - Estrogen receptors (ER), namely ERalpha and ERbeta, are hormone-activated
      transcription factors with an important role in carcinogenesis. In the present
      study, we aimed at elucidating the implication of ERalpha in skin cancer, using
      chemically-induced mouse skin tumours, as well as cell lines representing
      distinct stages of mouse skin oncogenesis. First, using immunohistochemical
      staining we showed that ERalpha is markedly increased in aggressive mouse skin
      tumours in vivo as compared to the papilloma tumours, whereas ERbeta levels are
      low and become even lower in the aggressive spindle tumours of carcinogen-treated
      mice. Then, using the multistage mouse skin carcinogenesis model, we showed that
      ERalpha gradually increases during promotion and progression stages of mouse skin
      carcinogenesis, peaking at the most aggressive stage, whereas ERbeta levels only
      slightly change throughout skin carcinogenesis. Stable transfection of the
      aggressive, spindle CarB cells with a dominant negative form of ERalpha
      (dnERalpha) resulted in reduced ERalpha levels and reduced binding to estrogen
      responsive elements (ERE)-containing sequences. We characterized two highly
      conserved EREs on the mouse ERalpha promoter through which dnERalpha decreased
      endogenous ERalpha levels. The dnERalpha-transfected CarB cells presented altered
      protein levels of cytoskeletal and cell adhesion molecules, slower growth rate
      and impaired anchorage-independent growth in vitro, whereas they gave smaller
      tumours with extended latency period of tumour onset in vivo. Our findings
      suggest an implication of ERalpha in the aggressiveness of spindle mouse skin
      cancer cells, possibly through regulation of genes affecting cell shape and
      adhesion, and they also provide hints for the effective targeting of spindle
      cancer cells by dnERalpha.

PMID- 22870270
TI  - Identification of fibrin clot-bound plasma proteins.
AB  - Several proteins are known to bind to a fibrin network and to change clot
      properties or function. In this study we aimed to get an overview of fibrin clot
      bound plasma proteins. A plasma clot was formed by adding thrombin, CaCl(2) and
      aprotinin to citrated platelet-poor plasma and unbound proteins were washed away
      with Tris-buffered saline. Non-covalently bound proteins were extracted,
      separated with 2D gel electrophoresis and visualized with Sypro Ruby. Excised
      protein spots were analyzed with mass spectrometry. The identity of the proteins
      was verified by checking the mass of the protein, and, if necessary, by Western
      blot analysis. Next to established fibrin-binding proteins we identified several
      novel fibrin clot-bound plasma proteins, including alpha(2)-macroglobulin,
      carboxypeptidase N, alpha(1)-antitrypsin, haptoglobin, serum amyloid P, and the
      apolipoproteins A-I, E, J, and A-IV. The latter six proteins are associated with
      high-density lipoprotein particles. In addition we showed that high-density
      lipoprotein associated proteins were also present in fibrinogen preparations
      purified from plasma. Most plasma proteins in a fibrin clot can be classified
      into three groups according to either blood coagulation, protease inhibition or
      high-density lipoprotein metabolism. The presence of high-density lipoprotein in
      clots might point to a role in hemostasis.

PMID- 22870271
TI  - CD47(low) status on CD4 effectors is necessary for the contraction/resolution of
      the immune response in humans and mice.
AB  - How do effector CD4 T cells escape cell death during the contraction of the
      immune response (IR) remain largely unknown. CD47, through interactions with
      thrombospondin-1 (TSP-1) and SIRP-alpha, is implicated in cell death and
      phagocytosis of malignant cells. Here, we reported a reduction in SIRP-alpha-Fc
      binding to effector memory T cells (T(EM)) and in vitro TCR-activated human CD4 T
      cells that was linked to TSP-1/CD47-induced cell death. The reduced SIRP-alpha-Fc
      binding (CD47(low) status) was not detected when CD4 T cells were stained with
      two anti-CD47 mAbs, which recognize distinct epitopes. In contrast, increased
      SIRP-alpha-Fc binding (CD47(high) status) marked central memory T cells (T(CM))
      as well as activated CD4 T cells exposed to IL-2, and correlated with resistance
      to TSP-1/CD47-mediated killing. Auto-aggressive CD4 effectors, which accumulated
      in lymph nodes and at mucosal sites of patients with Crohn's disease, displayed a
      CD47(high) status despite a high level of TSP-1 release in colonic tissues. In
      mice, CD47 (CD47(low) status) was required on antigen (Ag)-specific CD4 effectors
      for the contraction of the IR in vivo, as significantly lower numbers of Ag
      specific CD47(+/+)CD4 T cells were recovered when compared to Ag-specific CD47(-/
      ) CD4 T cells. In conclusion, we demonstrate that a transient change in the
      status of CD47, i.e. from CD47(high) to CD47(low), on CD4 effectors regulates the
      decision-making process that leads to CD47-mediated cell death and contraction of
      the IR while maintenance of a CD47(high) status on tissue-destructive CD4
      effectors prevents the resolution of the inflammatory response.

PMID- 22870272
TI  - Survivin is required for beta-cell mass expansion in the pancreatic duct-ligated
      mouse model.
AB  - AIMS/HYPOTHESIS: Pancreatic beta-cell mass expands through adulthood under
      certain conditions. The related molecular mechanisms are elusive. This study was
      designed to determine whether surviving (also known as Birc5), which is
      transiently expressed perinatally in islets, was required for beta-cell mass
      expansion in the pancreatic duct-ligated mouse model. METHODS: Mice with beta
      cell-specific deletion of survivin (RIPCre(+)survivin(fl/fl)) and their control
      littermates (RIPCre(+)survivin(+/+)) were examined to determine the essential
      role of survivin in partial pancreatic duct ligation (PDL)-induced beta-cell
      proliferation, function and survival. RESULTS: Resurgence of survivin expression
      occurred as early as day 3 post-PDL. By day 7 post-PDL, control mice showed
      significant expansion of beta-cell mass and increase in beta-cell proliferation
      and islet number in the ligated tail of the pancreas. However, mice deficient in
      beta-cell survivin showed a defect in beta-cell mass expansion and proliferation
      with a marked attenuation in the increase of total islet number, largely due to
      an impairment in the increase in number of larger islets while sparing the
      increase in number of small islets in the ligated tail of pancreas, resulting in
      insufficient insulin secretion and glucose intolerance. Importantly however, beta
      cell neogenesis and apoptosis were not affected by the absence of survivin in
      beta cells after PDL. CONCLUSIONS/INTERPRETATION: Our results indicate that
      survivin is essential for beta-cell mass expansion after PDL. Survivin appears to
      exhibit a preferential requirement for proliferation of preexisting beta cells.

PMID- 22870273
TI  - Evidence of melanoma in wild marine fish populations.
AB  - The increase in reports of novel diseases in a wide range of ecosystems, both
      terrestrial and marine, has been linked to many factors including exposure to
      novel pathogens and changes in the global climate. Prevalence of skin cancer in
      particular has been found to be increasing in humans, but has not been reported
      in wild fish before. Here we report extensive melanosis and melanoma (skin
      cancer) in wild populations of an iconic, commercially-important marine fish, the
      coral trout Plectropomus leopardus. The syndrome reported here has strong
      similarities to previous studies associated with UV induced melanomas in the well
      established laboratory fish model Xiphophorus. Relatively high prevalence rates
      of this syndrome (15%) were recorded at two offshore sites in the Great Barrier
      Reef Marine Park (GBRMP). In the absence of microbial pathogens and given the
      strong similarities to the UV-induced melanomas, we conclude that the likely
      cause was environmental exposure to UV radiation. Further studies are needed to
      establish the large scale distribution of the syndrome and confirm that the
      lesions reported here are the same as the melanoma in Xiphophorus, by assessing
      mutation of the EGFR gene, Xmrk. Furthermore, research on the potential links of
      this syndrome to increases in UV radiation from stratospheric ozone depletion
      needs to be completed.

PMID- 22870274
TI  - Phylogeography, risk factors and genetic history of hepatitis C virus in Gabon,
      central Africa.
AB  - BACKGROUND: The epidemiological and molecular characteristics of hepatitis C
      virus (HCV) infection in the general population have been poorly investigated in
      Africa. The aim of this study was to determine the prevalence, genotype
      distribution and epidemic history of HCV in the Gabonese general population.
      METHODS/PRINCIPAL FINDINGS: A total of 4042 sera collected from adults in 220
      villages in all nine administrative areas of the country were screened for
      antibodies to HCV. HCV NS5B region sequencing was performed for molecular
      characterization and population genetic analyses. Of 4042 tested sera, 455
      (11.2%) were positive. The seroprevalence of HCV varied significantly by
      administrative area, with the highest rate in Ogooue-Lolo province (20.4%) and
      the lowest in Ogooue-Maritine province (3.7%). History of parenteral injections,
      past hospital admission and age over 55 years were independent risk factors for
      HCV infection (p<0.0001). Phylogenetic analyses showed that 91.9% of the strains
      were genotype 4 (HCV-4), 5.7% genotype 1 and 2.2% genotype 2. HCV-4 strains were
      highly heterogeneous, with more than eight subtypes; subtype 4e predominated
      (57.3%). Coalescence analyses indicated that subtype 4e was the oldest, with an
      estimated most recent common ancestor of 1702 [95% CI, 1418-1884]. The epidemic
      profile indicated that it spread exponentially during the first part of the 20th
      century, probably by iatrogenic transmission. CONCLUSIONS/SIGNIFICANCE: These
      results confirm the endemicity of HCV subtype 4e in Gabon and show that its
      spread is due to a cohort effect, with previous, possibly iatrogenic events. More
      extensive epidemiological studies are needed to better characterize the route of
      transmission and the dissemination of HCV in Gabon.

PMID- 22870275
TI  - Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in
      cervical cancer.
AB  - The p53 tumor suppressor function can be compromised in many tumors by the
      cellular antagonist HDM2 and human papillomavirus oncogene E6 that induce p53
      degradation. Restoration of p53 activity has strong therapeutic potential. Here,
      we identified TSC-22 as a novel p53-interacting protein and show its novel
      function as a positive regulator of p53. We found that TSC-22 level was
      significantly down-regulated in cervical cancer tissues. Moreover, over
      expression of TSC-22 was sufficient to inhibit cell proliferation, promote
      cellular apoptosis in cervical cancer cells and suppress growth of xenograft
      tumors in mice. Expression of also TSC-22 enhanced the protein level of p53 by
      protecting it from poly-ubiquitination. When bound to the motif between amino
      acids 100 and 200 of p53, TSC-22 inhibited the HDM2- and E6-mediated p53 poly
      ubiquitination and degradation. Consequently, ectopic over-expression of TSC-22
      activated the function of p53, followed by increased expression of p21(Waf1/Cip1)
      and PUMA in human cervical cancer cell lines. Interestingly, TSC-22 did not
      affect the interaction between p53 and HDM2. Knock-down of TSC-22 by small
      interfering RNA clearly enhanced the poly-ubiquitination of p53, leading to the
      degradation of p53. These results suggest that TSC-22 acts as a tumor suppressor
      by safeguarding p53 from poly-ubiquitination mediated-degradation.

PMID- 22870276
TI  - Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2
      receptor, a class C GPCR.
AB  - The recent elucidation of the X-ray structure of several class A GPCRs clearly
      indicates that the amphipathic helix 8 (H8) is a conserved structural domain in
      most crystallized GPCRs. Very little is known about the presence and the possible
      role of an analogous H8 domain in the distantly related class C GPCRs. In this
      study, we investigated the structural properties for the H8 domain of the mGluR2
      receptor, a class C GPCR, by applying extended molecular dynamics simulations.
      Our study indicates that the amphipathic H8 adopts membrane-sensitive
      conformational states, which depend on the membrane composition. Cholesterol-rich
      membranes stabilize the helical structure of H8 whereas cholesterol-depleted
      membranes induce a disruption of H8. The observed link between membrane
      cholesterol levels and H8 conformational states suggests that H8 behaves as a
      sensor of cholesterol concentration.

PMID- 22870277
TI  - A transgenic transcription factor (TaDREB3) in barley affects the expression of
      microRNAs and other small non-coding RNAs.
AB  - Transcription factors (TFs), microRNAs (miRNAs), small interfering RNAs (siRNAs)
      and other functional non-coding small RNAs (sRNAs) are important gene regulators.
      Comparison of sRNA expression profiles between transgenic barley over-expressing
      a drought tolerant TF (TaDREB3) and non-transgenic control barley revealed many
      group-specific sRNAs. In addition, 42% of the shared sRNAs were differentially
      expressed between the two groups (|log(2)| >1). Furthermore, TaDREB3-derived
      sRNAs were only detected in transgenic barley despite the existence of homologous
      genes in non-transgenic barley. These results demonstrate that the TF strongly
      affects the expression of sRNAs and siRNAs could in turn affect the TF stability.
      The TF also affects size distribution and abundance of sRNAs including miRNAs.
      About half of the sRNAs in each group were derived from chloroplast. A sRNA
      derived from tRNA-His(GUG) encoded by the chloroplast genome is the most abundant
      sRNA, accounting for 42.2% of the total sRNAs in transgenic barley and 28.9% in
      non-transgenic barley. This sRNA, which targets a gene (TC245676) involved in
      biological processes, was only present in barley leaves but not roots. 124 and
      136 miRNAs were detected in transgenic and non-transgenic barley, respectively.
      miR156 was the most abundant miRNA and up-regulated in transgenic barley, while
      miR168 was the most abundant miRNA and up-regulated in non-transgenic barley.
      Eight out of 20 predicted novel miRNAs were differentially expressed between the
      two groups. All the predicted novel miRNA targets were validated using a
      degradome library. Our data provide an insight into the effect of TF on the
      expression of sRNAs in barley.

PMID- 22870279
TI  - Nuclear respiratory factor 1 mediates the transcription initiation of insulin
      degrading enzyme in a TATA box-binding protein-independent manner.
AB  - CpG island promoters often lack canonical core promoter elements such as the TATA
      box, and have dispersed transcription initiation sites. Despite the prevalence of
      CpG islands associated with mammalian genes, the mechanism of transcription
      initiation from CpG island promoters remains to be clarified. Here we investigate
      the mechanism of transcription initiation of the CpG island-associated gene,
      insulin-degrading enzyme (IDE). IDE is ubiquitously expressed, and has dispersed
      transcription initiation sites. The IDE core promoter locates within a 32-bp
      region, which contains three CGGCG repeats and a nuclear respiratory factor 1
      (NRF-1) binding motif. Sequential mutation analysis indicates that the NRF-1
      binding motif is critical for IDE transcription initiation. The NRF-1 binding
      motif is functional, because NRF-1 binds to this motif in vivo and this motif is
      required for the regulation of IDE promoter activity by NRF-1. Furthermore, the
      NRF-1 binding site in the IDE promoter is conserved among different species, and
      dominant negative NRF-1 represses endogenous IDE expression. Finally, TATA-box
      binding protein (TBP) is not associated with the IDE promoter, and inactivation
      of TBP does not abolish IDE transcription, suggesting that TBP is not essential
      for IDE transcription initiation. Our studies indicate that NRF-1 mediates IDE
      transcription initiation in a TBP-independent manner, and provide insights into
      the potential mechanism of transcription initiation for other CpG island
      associated genes.

PMID- 22870278
TI  - MicroRNA-34a modulates MDM4 expression via a target site in the open reading
      frame.
AB  - BACKGROUND: MDM4, also called MDMX or HDMX in humans, is an important negative
      regulator of the p53 tumor suppressor. MDM4 is overexpressed in about 17% of all
      cancers and more frequently in some types, such as colon cancer or
      retinoblastoma. MDM4 is known to be post-translationally regulated by MDM2
      mediated ubiquitination to decrease its protein levels in response to genotoxic
      stress, resulting in accumulation and activation of p53. At the transcriptional
      level, MDM4 gene regulation has been less clearly understood. We have reported
      that DNA damage triggers loss of MDM4 mRNA and a concurrent increase in p53
      activity. These experiments attempt to determine a mechanism for down-regulation
      of MDM4 mRNA. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that MDM4 mRNA is a
      target of hsa-mir-34a (miR-34a). MDM4 mRNA contains a lengthy 3' untranslated
      region; however, we find that it is a miR-34a site within the open reading frame
      (ORF) of exon 11 that is responsible for the repression. Overexpression of miR
      34a, but not a mutant miR-34a, is sufficient to decrease MDM4 mRNA levels to an
      extent identical to those of known miR-34a target genes. Likewise, MDM4 protein
      levels are decreased by miR-34a overexpression. Inhibition of endogenous miR-34a
      increased expression of miR-34a target genes and MDM4. A portion of MDM4 exon 11
      containing this 8mer-A1 miR-34a site fused to a luciferase reporter gene is
      sufficient to confer responsiveness, being inhibited by additional expression of
      exogenous mir-34a and activated by inhibition of miR-34a.
      CONCLUSIONS/SIGNIFICANCE: These data establish a mechanism for the observed DNA
      damage-induced negative regulation of MDM4 and potentially provide a novel means
      to manipulate MDM4 expression without introducing DNA damage.

PMID- 22870280
TI  - Transgenic resistance confers effective field level control of bacterial spot
      disease in tomato.
AB  - We investigated whether lines of transgenic tomato (Solanum lycopersicum)
      expressing the Bs2 resistance gene from pepper, a close relative of tomato,
      demonstrate improved resistance to bacterial spot disease caused by Xanthomonas
      species in replicated multi-year field trials under commercial type growing
      conditions. We report that the presence of the Bs2 gene in the highly susceptible
      VF 36 background reduced disease to extremely low levels, and VF 36-Bs2 plants
      displayed the lowest disease severity amongst all tomato varieties tested,
      including commercial and breeding lines with host resistance. Yields of
      marketable fruit from transgenic lines were typically 2.5 times that of the non
      transformed parent line, but varied between 1.5 and 11.5 fold depending on
      weather conditions and disease pressure. Trials were conducted without
      application of any copper-based bactericides, presently in wide use despite
      negative impacts on the environment. This is the first demonstration of effective
      field resistance in a transgenic genotype based on a plant R gene and provides an
      opportunity for control of a devastating pathogen while eliminating ineffective
      copper pesticides.

PMID- 22870281
TI  - Nitrogen and phosphorus limitation over long-term ecosystem development in
      terrestrial ecosystems.
AB  - Nutrient limitation to net primary production (NPP) displays a diversity of
      patterns as ecosystems develop over a range of timescales. For example, some
      ecosystems transition from N limitation on young soils to P limitation on
      geologically old soils, whereas others appear to remain N limited. Under what
      conditions should N limitation and P limitation prevail? When do transitions
      between N and P limitation occur? We analyzed transient dynamics of multiple
      timescales in an ecosystem model to investigate these questions. Post-disturbance
      dynamics in our model are controlled by a cascade of rates, from plant uptake
      (very fast) to litter turnover (fast) to plant mortality (intermediate) to plant
      unavailable nutrient loss (slow) to weathering (very slow). Young ecosystems are
      N limited when symbiotic N fixation (SNF) is constrained and P weathering inputs
      are high relative to atmospheric N deposition and plant N:P demand, but P limited
      under opposite conditions. In the absence of SNF, N limitation is likely to
      worsen through succession (decades to centuries) because P is mineralized faster
      than N. Over long timescales (centuries and longer) this preferential P
      mineralization increases the N:P ratio of soil organic matter, leading to greater
      losses of plant-unavailable N versus P relative to plant N:P demand. These loss
      dynamics favor N limitation on older soils despite the rising organic matter N:P
      ratio. However, weathering depletion favors P limitation on older soils when
      continual P inputs (e.g., dust deposition) are low, so nutrient limitation at the
      terminal equilibrium depends on the balance of these input and loss effects. If
      NPP switches from N to P limitation over long time periods, the transition time
      depends most strongly on the P weathering rate. At all timescales SNF has the
      capacity to overcome N limitation, so nutrient limitation depends critically on
      limits to SNF.

PMID- 22870282
TI  - Characterization of model peptide adducts with reactive metabolites of
      naphthalene by mass spectrometry.
AB  - Naphthalene is a volatile polycyclic aromatic hydrocarbon generated during
      combustion and is a ubiquitous chemical in the environment. Short term exposures
      of rodents to air concentrations less than the current OSHA standard yielded
      necrotic lesions in the airways and nasal epithelium of the mouse, and in the
      nasal epithelium of the rat. The cytotoxic effects of naphthalene have been
      correlated with the formation of covalent protein adducts after the generation of
      reactive metabolites, but there is little information about the specific sites of
      adduction or on the amino acid targets of these metabolites. To better understand
      the chemical species produced when naphthalene metabolites react with proteins
      and peptides, we studied the formation and structure of the resulting adducts
      from the incubation of model peptides with naphthalene epoxide, naphthalene diol
      epoxide, 1,2-naphthoquinone, and 1,4-naphthoquinone using high resolution mass
      spectrometry. Identification of the binding sites, relative rates of depletion of
      the unadducted peptide, and selectivity of binding to amino acid residues were
      determined. Adduction occurred on the cysteine, lysine, and histidine residues,
      and on the N-terminus. Monoadduct formation occurred in 39 of the 48 reactions.
      In reactions with the naphthoquinones, diadducts were observed, and in one case,
      a triadduct was detected. The results from this model peptide study will assist
      in data interpretation from ongoing work to detect peptide adducts in vivo as
      markers of biologic effect.

PMID- 22870283
TI  - Leishmania promastigotes lack phosphatidylserine but bind annexin V upon
      permeabilization or miltefosine treatment.
AB  - The protozoan parasite Leishmania is an intracellular pathogen infecting and
      replicating inside vertebrate host macrophages. A recent model suggests that
      promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells
      by exposing phosphatidylserine (PS) at the cell surface to trigger their
      phagocytic uptake into host macrophages. PS presentation at the cell surface is
      typically analyzed using fluorescence-labeled annexin V. Here we show that
      Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon
      permeabilization or miltefosine treatment. However, combined lipid analysis by
      thin-layer chromatography, mass spectrometry and (31)P nuclear magnetic resonance
      (NMR) spectroscopy revealed that Leishmania promastigotes lack any detectable
      amount of PS. Instead, we identified several other phospholipid classes such
      phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and
      phosphatidylinositol as candidate lipids enabling annexin V staining.

PMID- 22870284
TI  - Alcohol use in adolescence and risk of disability pension: a 39 year follow-up of
      a population-based conscription survey.
AB  - BACKGROUND: The role of alcohol consumption for disability pension (DP) is
      controversial and systematic reviews have not established causality. We aimed to
      assess the role of adolescent alcohol use for future DP. We wanted to find out
      whether an increased risk mainly would affect DP occurring early or late in life
      as well as whether the level of alcohol consumption and patterns of drinking
      contribute differently in DP receiving. METHODOLOGY/PRINCIPAL FINDINGS: The study
      is a 39-year follow-up of 49 321 Swedish men born in 1949-1951 and conscripted
      for compulsory military service in 1969-1970. As study exposures (i) "risk use"
      of alcohol composed of measures related to pattern of drinking, and (ii) the
      level of consumption based on self-reported volume and frequency of drinking had
      been used. Information on DP was obtained from social insurance databases through
      2008. "Risk use" of alcohol was associated with both "early DP" and "late DP",
      i.e. granted below and above the approximate age of 40 years, with crude hazard
      ratio (HR) of 2.89 (95% confidence intervals (CI) 2.47-3.38) and HR of 1.87
      (95%CI: 1.74-2.02), respectively. After adjustment for covariates, HR was reduced
      to 1.32 (95%CI: 1.09-1.59) and 1.14 (95%CI: 1.05-1.25), respectively. Similar
      patterns were seen for moderate (101-250 g 100% alcohol/week) and high (>250 g)
      consumption, though the risk disappeared when fully adjusted.
      CONCLUSIONS/SIGNIFICANCE: Alcohol use in adolescence, particularly measured as
      "risk use", is associated with increased risk of future DP. The association is
      stronger for "early DP", but remains significant even for DP granted in older
      ages. Therefore, pattern of drinking in adolescent should be considered an
      important marker for future reduced work capacity.

PMID- 22870285
TI  - Molecular breeding of a fungus producing a precursor diterpene suitable for semi
      synthesis by dissection of the biosynthetic machinery.
AB  - Many clinically useful pharmaceuticals are semi-synthesized from natural products
      produced by actinobacteria and fungi. The synthetic protocols usually contain
      many complicated reaction steps and thereby result in low yields and high costs.
      It is therefore important to breed microorganisms that produce a compound most
      suitable for chemical synthesis. For a long time, desirable mutants have been
      obtained by random mutagenesis and mass screening. However, these mutants
      sometimes show unfavorable phenotypes such as low viability and low productivity
      of the desired compound. Fusicoccin (FC) A is a diterpene glucoside produced by
      the fungus Phomopsis amygdali. Both FC and the structurally-related cotylenin A
      (CN) have phytohormone-like activity. However, only CN exhibits anti-cancer
      activity. Since the CN producer lost its ability to proliferate during
      preservation, a study on the relationship between structure and activity was
      carried out, and elimination of the hydroxyl group at position 12 of FC was
      essential to mimic the CN-like activity. Based on detailed dissection of the
      biosynthetic machinery, we constructed a mutant producing a compound without a
      hydroxyl group at position 12 by gene-disruption. The mutant produced this
      compound as a sole metabolite, which can be easily and efficiently converted into
      an anti-cancer drug, and its productivity was equivalent to the sum of FC-related
      compounds produced by the parental strain. Our strategy would be applicable to
      development of pharmaceuticals that are semi-synthesized from fungal metabolites.

PMID- 22870286
TI  - Automating digital leaf measurement: the tooth, the whole tooth, and nothing but
      the tooth.
AB  - Many species of plants produce leaves with distinct teeth around their margins.
      The presence and nature of these teeth can often help botanists to identify
      species. Moreover, it has long been known that more species native to colder
      regions have teeth than species native to warmer regions. It has therefore been
      suggested that fossilized remains of leaves can be used as a proxy for ancient
      climate reconstruction. Similar studies on living plants can help our
      understanding of the relationships. The required analysis of leaves typically
      involves considerable manual effort, which in practice limits the number of
      leaves that are analyzed, potentially reducing the power of the results. In this
      work, we describe a novel algorithm to automate the marginal tooth analysis of
      leaves found in digital images. We demonstrate our methods on a large set of
      images of whole herbarium specimens collected from Tilia trees (also known as
      lime, linden or basswood). We chose the genus Tilia as its constituent species
      have toothed leaves of varied size and shape. In a previous study we extracted
      c.1600 leaves automatically from a set of c.1100 images. Our new algorithm
      locates teeth on the margins of such leaves and extracts features such as each
      tooth's area, perimeter and internal angles, as well as counting them. We
      evaluate an implementation of our algorithm's performance against a manually
      analyzed subset of the images. We found that the algorithm achieves an accuracy
      of 85% for counting teeth and 75% for estimating tooth area. We also demonstrate
      that the automatically extracted features are sufficient to identify different
      species of Tilia using a simple linear discriminant analysis, and that the
      features relating to teeth are the most useful.

PMID- 22870287
TI  - Enhanced cellulose degradation using cellulase-nanosphere complexes.
AB  - Enzyme catalyzed conversion of plant biomass to sugars is an inherently
      inefficient process, and one of the major factors limiting economical biofuel
      production. This is due to the physical barrier presented by polymers in plant
      cell walls, including semi-crystalline cellulose, to soluble enzyme
      accessibility. In contrast to the enzymes currently used in industry, bacterial
      cellulosomes organize cellulases and other proteins in a scaffold structure, and
      are highly efficient in degrading cellulose. To mimic this clustered assembly of
      enzymes, we conjugated cellulase obtained from Trichoderma viride to polystyrene
      nanospheres (cellulase:NS) and tested the hydrolytic activity of this complex on
      cellulose substrates from purified and natural sources. Cellulase:NS and free
      cellulase were equally active on soluble carboxymethyl cellulose (CMC); however,
      the complexed enzyme displayed a higher affinity in its action on
      microcrystalline cellulose. Similarly, we found that the cellulase:NS complex was
      more efficient in degrading natural cellulose structures in the thickened walls
      of cultured wood cells. These results suggest that nanoparticle-bound enzymes can
      improve catalytic efficiency on physically intractable substrates. We discuss the
      potential for further enhancement of cellulose degradation by physically
      clustering combinations of different glycosyl hydrolase enzymes, and applications
      for using cellulase:NS complexes in biofuel production.

PMID- 22870288
TI  - HSPB2 is dispensable for the cardiac hypertrophic response but reduces
      mitochondrial energetics following pressure overload in mice.
AB  - BACKGROUND: CryAB (HspB5) and HspB2, two small heat shock genes located
      adjacently in the vertebrate genome, are hypothesized to play distinct roles.
      Mice lacking both cryab and hspb2 (DKO) are viable and exhibit adult-onset
      degeneration of skeletal muscle but confounding results from independent groups
      were reported for cardiac responses to different stressful conditions (i.e.,
      ischemia/reperfusion or pressure overload). To determine the specific
      requirements of HSPB2 in heart, we generated cardiac-specific HSPB2 deficient
      (HSPB2cKO) mice and examined their cardiac function under basal conditions and
      following cardiac pressure overload. METHODOLOGY/PRINCIPAL FINDINGS: Transverse
      aortic constriction (TAC) or sham surgery was performed in HSPB2cKO mice and
      their littermates (HSPB2wt mice). Eight weeks after TAC, we found that expression
      of several small HSPs (HSPB2, 5, 6) was not markedly modified in HSPB2wt mice.
      Both cardiac function and the hypertrophic response remained similar in HSPB2cKO
      and HSPB2wt hearts. In addition, mitochondrial respiration and ATP production
      assays demonstrated that the absence of HSPB2 did not change mitochondrial
      metabolism in basal conditions. However, fatty acid supported state 3 respiration
      rate (ADP stimulated) in TAC operated HSPB2cKO hearts was significantly reduced
      in compared with TAC operated HSPB2wt mice (10.5+/-2.2 vs. 12.8+/-2.5 nmol
      O(2)/min/mg dry fiber weight, P<0.05), and ATP production in HSPB2cKO hearts was
      significantly reduced in TAC compared with sham operated mice (29.8+/-0.2 vs.
      21.1+/-1.8 nmol ATP/min/mg dry fiber weight, P<0.05). Although HSPB2 was not
      associated with mitochondria under cardiac stress, absence of HSPB2 led to
      changes in transcript levels of several metabolic and mitochondrial regulator
      genes. CONCLUSIONS/SIGNIFICANCE: The present study indicates that HSPB2 can be
      replaced by other members of the multigene small HSP family under basal
      conditions while HSPB2 is implicated in the regulation of metabolic/mitochondrial
      function under cardiac stress such pressure overload.

PMID- 22870289
TI  - Exposure to secondhand smoke in terraces and other outdoor areas of hospitality
      venues in eight European countries.
AB  - BACKGROUND: Outdoor secondhand smoke (SHS) concentrations are usually lower than
      indoor concentrations, yet some studies have shown that outdoor SHS levels could
      be comparable to indoor levels under specific conditions. The main objectives of
      this study were to assess levels of SHS exposure in terraces and other outdoor
      areas of hospitality venues and to evaluate their potential displacement to
      adjacent indoor areas. METHODS: Nicotine and respirable particles (PM2.5) were
      measured in outdoor and indoor areas of hospitality venues of 8 European
      countries. Hospitality venues of the study included night bars, restaurants and
      bars. The fieldwork was carried out between March 2009 and March 2011. RESULTS:
      We gathered 170 nicotine and 142 PM2.5 measurements during the study. The median
      indoor SHS concentration was significantly higher in venues where smoking was
      allowed (nicotine 3.69 ug/m3, PM2.5: 120.51 ug/m3) than in those where smoking
      was banned (nicotine: 0.48 ug/m3, PM2.5: 36.90 ug/m3). The median outdoor
      nicotine concentration was higher in places where indoor smoking was banned (1.56
      ug/m3) than in venues where smoking was allowed (0.31 ug/m3). Among the different
      types of outdoor areas, the highest median outdoor SHS levels (nicotine: 4.23
      ug/m3, PM2.5: 43.64 ug/m3) were found in the semi-closed outdoor areas of venues
      where indoor smoking was banned. CONCLUSIONS: Banning indoor smoking seems to
      displace SHS exposure to adjacent outdoor areas. Furthermore, indoor settings
      where smoking is banned but which have a semi-closed outdoor area have higher
      levels of SHS than those with open outdoor areas, possibly indicating that SHS
      also drifts from outdoors to indoors. Current legislation restricting indoor SHS
      levels seems to be insufficient to protect hospitality workers--and patrons--from
      SHS exposure. Tobacco-free legislation should take these results into account and
      consider restrictions in the terraces of some hospitality venues to ensure
      effective protection.

PMID- 22870291
TI  - High rates of detection of respiratory viruses in tonsillar tissues from children
      with chronic adenotonsillar disease.
AB  - Chronic tonsillar diseases are an important health problem, leading to large
      numbers of surgical procedures worldwide. Little is known about pathogenesis of
      these diseases. In order to investigate the role of respiratory viruses in
      chronic adenotonsillar diseases, we developed a cross-sectional study to
      determine the rates of viral detections of common respiratory viruses detected by
      TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and
      peripheral blood from 121 children with chronic tonsillar diseases, without
      symptoms of acute respiratory infections. At least one respiratory virus was
      detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most
      frequently detected viruses were human adenovirus in 47.1%, human enterovirus in
      40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus
      in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied
      widely between sample sites: human adenovirus, human bocavirus and human
      enterovirus were predominantly detected in tissues, while human rhinovirus was
      more frequently detected in secretions. Rates of virus detection were remarkably
      high in tonsil tissues: over 85% in adenoids and close to 70% in palatine
      tonsils. In addition, overall virus detection rates were higher in more
      hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of
      human enteroviruses, they were detected more frequently (p = 0.05) in larger
      palatine tonsils than in smaller ones. While persistence/latency of DNA viruses
      in tonsillar tissues has been documented, such is not the case of RNA viruses.
      Respiratory viruses are highly prevalent in adenoids and palatine tonsils of
      patients with chronic tonsillar diseases, and persistence of these viruses in
      tonsils may stimulate chronic inflammation and play a role in the pathogenesis of
      these diseases.

PMID- 22870290
TI  - Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet
      induced obese AKR/J mice.
AB  - An increasing amount of evidence supports pleiotropic metabolic roles of the
      cannibinoid-1 receptor (CB1R) in peripheral tissues such as adipose, liver,
      skeletal muscle and pancreas. To further understand the metabolic consequences of
      specific blockade of CB1R function in peripheral tissues, we performed a 10-week
      study with an anti-sense oligonucleotide directed against the CB1R in diet
      induced obese (DIO) AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis
      414930 (6.25, 12.5 and 25 mg/kg/week) or control ASO Isis-141923 (25 mg/kg/week)
      via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R
      mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was
      decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose
      dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group
      (46.1+/-1.0 g vs veh, 51.2+/-0.9 g, p<0.05). Body fat mass was reduced in
      parallel with attenuated body weight gain. CB1R ASO treatment led to decreased
      fed glucose level (at week 8, 25 mg/kg/week group, 145+/-4 mg/dL vs veh, 195+/-10
      mg/dL, p<0.05). Moreover, CB1R ASO treatment dose-dependently improved glucose
      excursion during an oral glucose tolerance test, whereas control ASO exerted no
      effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of
      the study, plasma insulin and leptin levels were significantly reduced by 25
      mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both
      epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were
      also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led
      to improved insulin sensitivity and glucose homeostasis. The beneficial effects
      of CB1R ASO treatment strongly support the notion that selective inhibition of
      the peripheral CB1R, without blockade of central CB1R, may serve as an effective
      approach for treating type II diabetes, obesity and the metabolic syndrome.

PMID- 22870292
TI  - Combining [11C]-AnxA5 PET imaging with serum biomarkers for improved detection in
      live mice of modest cell death in human solid tumor xenografts.
AB  - BACKGROUND: In vivo imaging using Annexin A5-based radioligands is a powerful
      technique for visualizing massive cell death, but has been less successful in
      monitoring the modest cell death typically seen in solid tumors after
      chemotherapy. Here we combined dynamic positron emission tomography (PET) imaging
      using Annexin A5 with a serum-based apoptosis marker, for improved sensitivity
      and specificity in assessment of chemotherapy-induced cell death in a solid tumor
      model. METHODOLOGY/PRINCIPAL FINDINGS: Modest cell death was induced by
      doxorubicin in a mouse xenograft model with human FaDu head and neck cancer
      cells. PET imaging was based on (11)C-labeled Sel-tagged Annexin A5 ([(11)C]
      AnxA5-ST) and a size-matched control. 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]
      FDG) was utilized as a tracer of tissue metabolism. Serum biomarkers for cell
      death were ccK18 and K18 (M30 Apoptosense(r) and M65). Apoptosis in tissue
      sections was verified ex vivo for validation. Both PET imaging using [(11)C]
      AnxA5-ST and serum ccK18/K18 levels revealed treatment-induced cell death, with
      ccK18 displaying the highest detection sensitivity. [(18)F]-FDG uptake was not
      affected by this treatment in this tumor model. [(11)C]-AnxA5-ST gave robust
      imaging readouts at one hour and its short half-life made it possible to perform
      paired scans in the same animal in one imaging session. CONCLUSIONS/SIGNIFICANCE:
      The combined use of dynamic PET with [(11)C]-AnxA5-ST, showing specific increases
      in tumor binding potential upon therapy, with ccK18/K18 serum measurements, as
      highly sensitive markers for cell death, enabled effective assessment of modest
      therapy-induced cell death in this mouse xenograft model of solid human tumors.

PMID- 22870294
TI  - The influence of coral reef benthic condition on associated fish assemblages.
AB  - Accumulative disturbances can erode a coral reef's resilience, often leading to
      replacement of scleractinian corals by macroalgae or other non-coral organisms.
      These degraded reef systems have been mostly described based on changes in the
      composition of the reef benthos, and there is little understanding of how such
      changes are influenced by, and in turn influence, other components of the reef
      ecosystem. This study investigated the spatial variation in benthic communities
      on fringing reefs around the inner Seychelles islands. Specifically,
      relationships between benthic composition and the underlying substrata, as well
      as the associated fish assemblages were assessed. High variability in benthic
      composition was found among reefs, with a gradient from high coral cover (up to
      58%) and high structural complexity to high macroalgae cover (up to 95%) and low
      structural complexity at the extremes. This gradient was associated with
      declining species richness of fishes, reduced diversity of fish functional
      groups, and lower abundance of corallivorous fishes. There were no reciprocal
      increases in herbivorous fish abundances, and relationships with other fish
      functional groups and total fish abundance were weak. Reefs grouping at the
      extremes of complex coral habitats or low-complexity macroalgal habitats
      displayed markedly different fish communities, with only two species of benthic
      invertebrate feeding fishes in greater abundance in the macroalgal habitat. These
      results have negative implications for the continuation of many coral reef
      ecosystem processes and services if more reefs shift to extreme degraded
      conditions dominated by macroalgae.

PMID- 22870293
TI  - Evaluation of a diet quality index based on the probability of adequate nutrient
      intake (PANDiet) using national French and US dietary surveys.
AB  - BACKGROUND: Existing diet quality indices often show theoretical and
      methodological limitations, especially with regard to validation. OBJECTIVE: To
      develop a diet quality index based on the probability of adequate nutrient intake
      (PANDiet) and evaluate its validity using data from French and US populations.
      MATERIAL AND METHODS: The PANDiet is composed of adequacy probabilities for 24
      nutrients grouped into two sub-scores. The relationship between the PANDiet score
      and energy intake were investigated. We evaluated the construct validity of the
      index by comparing scores for population sub-groups with 'a priori' differences
      in diet quality, according to smoking status, energy density, food intakes,
      plasma folate and carotenoid concentrations. French and US implementations of the
      PANDiet were developed and evaluated using national nutritional recommendations
      and dietary surveys. RESULTS: The PANDiet was not correlated with energy for the
      French implementation (r = -0.02, P>0.05) and correlated at a low level for the
      US implementation (r = -0.11, P<0.0001). In both implementations, a higher
      PANDiet score (i.e. a better diet quality) was associated with not smoking,
      having a lower-energy-dense diet, consuming higher amounts of fruits, vegetables,
      fish, milk and other dairy products and lower amounts of cheese, pizza, eggs,
      meat and processed meat, and having higher plasma folate and carotenoid
      concentrations after controlling for appropriate factors (all P<0.05, carotenoid
      data for US not available). CONCLUSIONS: The PANDiet provides a single score that
      measures the adequacy of nutrient intake and reflects diet quality. This index is
      adaptable for use in different countries and relevant at the individual and
      population levels.

PMID- 22870295
TI  - An overgrowth disorder associated with excessive production of cGMP due to a gain
      of-function mutation of the natriuretic peptide receptor 2 gene.
AB  - We describe a three-generation family with tall stature, scoliosis and
      macrodactyly of the great toes and a heterozygous p.Val883Met mutation in Npr2,
      the gene that encodes the CNP receptor NPR2 (natriuretic peptide receptor 2).
      When expressed in HEK293A cells, the mutant Npr2 cDNA generated intracellular
      cGMP (cyclic guanosine monophosphate) in the absence of CNP ligand. In the
      presence of CNP, cGMP production was greater in cells that had been transfected
      with the mutant Npr2 cDNA compared to wild-type cDNA. Transgenic mice in which
      the mutant Npr2 was expressed in chondrocytes driven by the promoter and intronic
      enhancer of the Col11a2 gene exhibited an enhanced production of cGMP in
      cartilage, leading to a similar phenotype to that observed in the patients. In
      addition, blood cGMP concentrations were elevated in the patients. These results
      indicate that p.Val883Met is a constitutive active gain-of-function mutation and
      elevated levels of cGMP in growth plates lead to the elongation of long bones.
      Our findings reveal a critical role for NPR2 in skeletal growth in both humans
      and mice, and may provide a potential target for prevention and treatment of
      diseases caused by impaired production of cGMP.

PMID- 22870296
TI  - Identification and characterization of ZEL-H16 as a novel agonist of the
      histamine H3 receptor.
AB  - The histamine H3 receptor (H3R) has been recognized as a promising target for the
      treatment of various central and peripheral nervous system diseases. In this
      study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3
      receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of
      approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated
      that ZEL-H16 behaved as a partial agonist on the inhibition of forskolin
      stimulated cAMP accumulation (the efficacy was 60% of that of histamine) and
      activation of ERK1/2 signaling (the efficacy was 50% of that of histamine) at H3
      receptors, but acted as a full agonist just like histamin in the guinea-pig ileum
      contraction assay. These effects were blocked by pertussis toxin and H3 receptor
      specific antagonist thioperamide. ZEL-H16 showed no agonist or antagonist
      activities at the cloned human histamine H1, H2, and H4 receptors and other
      biogenic amine GPCRs in the CRE-driven reporter assay. Furthermore, our present
      data demonstrated that treatment of ZEL-H16 resulted in intensive H3 receptor
      internalization and delayed recycling to the cell surface as compared to that of
      control with treatment of histamine. Thus, ZEL-H16 is a novel and potent
      nonimidazole agonist of H3R, which might serve as a pharmacological tool for
      future investigations or as possible therapeutic agent of H3R.

PMID- 22870297
TI  - Imaging lung function in mice using SPECT/CT and per-voxel analysis.
AB  - Chronic lung disease is a major worldwide health concern but better tools are
      required to understand the underlying pathologies. Ventilation/perfusion (V/Q)
      single photon emission computed tomography (SPECT) with per-voxel analysis allows
      for non-invasive measurement of regional lung function. A clinically adapted V/Q
      methodology was used in healthy mice to investigate V/Q relationships. Twelve
      week-old mice were imaged to describe normal lung function while 36 week-old mice
      were imaged to determine how age affects V/Q. Mice were ventilated with
      TechnegasTM and injected with (99m)Tc-macroaggregated albumin to trace
      ventilation and perfusion, respectively. For both processes, SPECT and CT images
      were acquired, co-registered, and quantitatively analyzed. On a per-voxel basis,
      ventilation and perfusion were moderately correlated (R = 0.58+/-0.03) in 12 week
      old animals and a mean log(V/Q) ratio of -0.07+/-0.01 and standard deviation of
      0.36+/-0.02 were found, defining the extent of V/Q matching. In contrast, 36 week
      old animals had significantly increased levels of V/Q mismatching throughout the
      periphery of the lung. Measures of V/Q were consistent across healthy animals and
      differences were observed with age demonstrating the capability of this technique
      in quantifying lung function. Per-voxel analysis and the ability to non
      invasively assess lung function will aid in the investigation of chronic lung
      disease models and drug efficacy studies.

PMID- 22870298
TI  - Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti
      CCP seropositivity.
AB  - OBJECTIVE: To examine the frequency and phenotype of Th17 cells in the peripheral
      blood of early RA (eRA) patients. METHODS: CD4+ T cells were isolated from the
      peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy
      controls (HC), and from the synovial fluid of 20 established RA patients (RASF),
      by ficoll-hypaque gradient and magnetical negative selection. After polyclonal
      stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry
      and concentrations of IL-17, IFN-gamma, TNF-alpha and IL-10 were measured by
      ELISA in cell-free supernatants. RESULTS: When all of our eRA patients were
      analyzed together, a significantly lower percentage of circulating Th17 cells and
      a lower CD4-derived IL-17 secretion were observed in comparison with HC. However,
      after stratifying by anti-CCP antibody status, circulating Th17 cells were
      decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were
      CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in
      anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated
      with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after
      initiating treatment with oral methotrexate, their circulating Th17 frequency was
      no longer different from HC. Of note, the percentage of circulating Th1 cells and
      the secretion of CD4-derived IFN-gamma, TNF-alpha and IL-10 were not different
      between eRA patients and HC. In established RA patients, circulating Th17 and
      T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells
      were increased when compared with blood of eRA patients, established RA patients
      and HC. CONCLUSION: Decreased circulating Th17 levels in eRA seem to be a marker
      of anti-CCP seropositivity, and return to levels observed in healthy controls
      after treatment with methotrexate.

PMID- 22870299
TI  - MicroRNA profiling of Epstein-Barr virus-associated NK/T-cell lymphomas by deep
      sequencing.
AB  - The Epstein-Barr virus (EBV) is an oncogenic human Herpes virus involved in the
      pathogenesis of nasal NK/T-cell lymphoma. EBV encodes microRNAs (miRNAs) and
      induces changes in the host cellular miRNA profile. MiRNAs are short non-coding
      RNAs of about 19-25 nt length that regulate gene expression by post
      transcriptional mechanisms and are frequently deregulated in human malignancies
      including cancer. The microRNA profiles of EBV-positive NK/T-cell lymphoma, non
      infected T-cell lymphoma and normal thymus were established by deep sequencing of
      small RNA libraries. The comparison of the EBV-positive NK/T-cell vs. EBV
      negative T-cell lymphoma revealed 15 up- und 16 down-regulated miRNAs. In
      contrast, the majority of miRNAs was repressed in the lymphomas compared to
      normal tissue. We also identified 10 novel miRNAs from known precursors and two
      so far unknown miRNAs. The sequencing results were confirmed for selected miRNAs
      by quantitative Real-Time PCR (qRT-PCR). We show that the proinflammatory
      cytokine interleukin 1 alpha (IL1A) is a target for miR-142-3p and the oncogenic
      BCL6 for miR-205. MiR-142-3p is down-regulated in the EBV-positive vs. EBV
      negative lymphomas. MiR-205 was undetectable in EBV-negative lymphoma and
      strongly down-regulated in EBV-positive NK/T-cell lymphoma as compared to thymus.
      The targets were confirmed by reporter assays and by down-regulation of the
      proteins by ectopic expression of the cognate miRNAs. Taken together, our
      findings demonstrate the relevance of deregulated miRNAs for the post
      transcriptional gene regulation in nasal NK/T-cell lymphomas.

PMID- 22870300
TI  - A method for quantifying mechanical properties of tissue following viral
      infection.
AB  - Viral infection and replication involves the reorganization of the actin network
      within the host cell. Actin plays a central role in the mechanical properties of
      cells. We have demonstrated a method to quantify changes in mechanical properties
      of fabricated model three-dimensional (3D) connective tissue following viral
      infection. Using this method, we have characterized the impact of infection by
      the human herpesvirus, cytomegalovirus (HCMV). HCMV is a member of the
      herpesvirus family and infects a variety of cell types including fibroblasts. In
      the body, fibroblasts are necessary for maintaining connective tissue and
      function by creating mechanical force. Using this 3D connective tissue model, we
      observed that infection disrupted the cell's ability to generate force and
      reduced the cumulative contractile force of the tissue. The addition of HCMV
      viral particles in the absence of both viral gene expression and DNA replication
      was sufficient to disrupt tissue function. We observed that alterations of the
      mechanical properties are, in part, due to a disruption of the underlying complex
      actin microfilament network established by the embedded fibroblasts. Finally, we
      were able to prevent HCMV-mediated disruption of tissue function by the addition
      of human immune globulin against HCMV. This study demonstrates a method to
      quantify the impact of viral infection on mechanical properties which are not
      evident using conventional cell culture systems.

PMID- 22870301
TI  - Comparative study of scientific publications in urology and nephrology journals
      originating from USA, China and Japan (2001-2010).
AB  - BACKGROUND: In the past decade, scientific research has developed rapidly in
      China, but the growth seems to vary widely between different disciplines. In this
      study, we aimed to compare the quantity and quality of publications in urology
      and nephrology journals from USA, China and Japan. METHODS: Journals listed in
      the "Urology and Nephrology" category of Science Citation Index Expanded subject
      categories were included. Scientific papers in these journals written by
      researchers from USA, Japan and China were retrieved from the "PubMed" and "Web
      of Knowledge" online databases. RESULTS: The annual number of total scientific
      articles increased significantly from 2001 to 2010 in China, and has ranked
      second in the world since 2006. In the field of urology and nephrology, the
      annual number increased significantly from 2001 to 2010 in USA and China; but not
      in Japan. The share of articles increased significantly over time in China,
      decreased significantly in Japan, and remained unchanged in USA. In 2010, USA
      contributed 32.17% of the total world output in urology and nephrology field and
      ranked 1(st); Japan contributed 5.19% and ranked 5(th); China contributed 3.83%
      and ranked 9(th). Publications from USA had the highest accumulated IFs and the
      highest total citations of articles (USA>Japan>China, p<0.001). No significant
      difference was found in average IF among the three countries. USA published the
      most articles in the top 10 urology and nephrology journals
      (USA(35165)>Japan(6704)>China(2233), p<0.001). Researchers from USA published
      more clinical trials and randomized controlled trials than Japan and China
      (USA>Japan>China, p<0.001). CONCLUSION: Although China has undergone significant
      increase in annual number and percentage of scientific publication in urology and
      nephrology journals in the past decade, it still lags far behind USA and Japan in
      the field of urology and nephrology in terms of quantity and quality.

PMID- 22870302
TI  - Quantitative proteomic analysis of the effect of fluoride on the acquired enamel
      pellicle.
AB  - The acquired enamel pellicle (AEP) is a thin film formed by the selective
      adsorption of salivary proteins onto the enamel surface of teeth. The AEP forms a
      critical interface between the mineral phase of teeth (hydroxyapatite) and the
      oral microbial biofilm. This biofilm is the key feature responsible for the
      development of dental caries. Fluoride on enamel surface is well known to reduce
      caries by reducing the solubility of enamel to acid. Information on the effects
      of fluoride on AEP formation is limited. This study aimed to investigate the
      effects of fluoride treatment on hydroxyapatite on the subsequent formation of
      AEP. In addition, this study pioneered the use of label-free quantitative
      proteomics to better understand the composition of AEP proteins. Hydroxyapatite
      discs were randomly divided in 4 groups (n = 10 per group). Each disc was exposed
      to distilled water (control) or sodium fluoride solution (1, 2 or 5%) for 2
      hours. Discs were then washed and immersed in human saliva for an additional 2
      hours. AEP from each disc was collected and subjected to liquid chromatography
      electrospray ionization mass spectrometry for protein identification,
      characterization and quantification. A total of 45 proteins were present in all
      four groups, 12 proteins were exclusively present in the control group and
      another 19 proteins were only present in the discs treated with 5% sodium
      fluoride. Relative proteomic quantification was carried out for the 45 proteins
      observed in all four groups. Notably, the concentration of important salivary
      proteins, such as statherin and histatin 1, decrease with increasing levels of
      fluoride. It suggests that these proteins are repulsed when hydroxyapatite
      surface is coated with fluoride. Our data demonstrated that treatment of
      hydroxyapatite with fluoride (at high concentration) qualitatively and
      quantitatively modulates AEP formation, effects which in turn will likely impact
      the formation of oral biofilms.

PMID- 22870303
TI  - An orphan chemotaxis sensor regulates virulence and antibiotic tolerance in the
      human pathogen Pseudomonas aeruginosa.
AB  - The synthesis of virulence factors by pathogenic bacteria is highly regulated and
      occurs in response to diverse environmental cues. An array of two component
      systems (TCSs) serves to link perception of different cues to specific changes in
      gene expression and/or bacterial behaviour. Those TCSs that regulate functions
      associated with virulence represent attractive targets for interference in anti
      infective strategies for disease control. We have previously identified PA2572 as
      a putative response regulator required for full virulence of Pseudomonas
      aeruginosa, the opportunistic human pathogen, to Galleria mellonella (Wax moth)
      larvae. Here we have investigated the involvement of candidate sensors for signal
      transduction involving PA2572. Mutation of PA2573, encoding a probable methyl
      accepting chemotaxis protein, gave rise to alterations in motility, virulence,
      and antibiotic resistance, functions which are also controlled by PA2572.
      Comparative transcriptome profiling of mutants revealed that PA2572 and PA2573
      regulate expression of a common set of 49 genes that are involved in a range of
      biological functions including virulence and antibiotic resistance. Bacterial two
      hybrid analysis indicated a REC-dependent interaction between PA2572 and PA2573
      proteins. Finally expression of PA2572 in the PA2573 mutant background restored
      virulence to G. mellonella towards wild-type levels. The findings indicate a role
      for the orphan chemotaxis sensor PA2573 in the regulation of virulence and
      antibiotic tolerance in P. aeruginosa and indicate that these effects are exerted
      in part through signal transduction involving PA2572.

PMID- 22870304
TI  - Evaluation of proxy tests for SFSN: evidence for mixed small and large fiber
      dysfunction.
AB  - BACKGROUND: Though intra-epidermal nerve fiber density (IENFD) is considered the
      gold standard for diagnosis of small fiber sensory neuropathy (SFSN), we aimed to
      determine if novel threshold values derived from standard tests of small or large
      fiber function could serve as diagnostic alternatives. METHODS: Seventy-four
      consecutive patients with painful polyneuropathy and normal nerve conduction
      studies (NCS) were defined as SFSN cases or controls by distal IENFD <5.4 and
      >=5.4 fibers/mm, respectively. Diagnostic performance of small fiber [cooling
      (CDT) and heat perception (HP) thresholds, axon reflex-mediated neurogenic
      vasodilatation] and large fiber function tests [vibration perception thresholds
      (VPT) and sural nerve conduction parameters] were determined by receiver
      operating-characteristic (ROC) curve analyses. RESULTS: The 26(35%) SFSN cases
      had mean IENFD 3.3+/-1.7 fibers/mm and the 48(65%) controls 9.9+/-2.9 fibers/mm.
      Male gender (p = 0.02) and older age (p = 0.02) were associated with SFSN cases
      compared to controls. VPT were higher and CDT lower in SFSN cases, but the
      largest magnitude of differences was observed for sural nerve amplitude. It had
      the greatest area under the ROC curve (0.75) compared to all other tests (p<0.001
      for all comparisons) and the optimal threshold value of <=12 uV defined SFSN
      cases with 80% sensitivity and 72% specificity. CONCLUSION: In patients
      presenting with polyneuropathy manifestations and normal NCS, though small fiber
      function tests were intuitively considered the best alternative measures to
      predict reduced IENFD, their diagnostic performance was poor. Instead, novel
      threshold values within the normal range for large fiber tests should be
      considered as an alternative strategy to select subjects for skin biopsy in
      diagnostic protocols for SFSN.

PMID- 22870306
TI  - The earliest matches.
AB  - Cylindrical objects made usually of fired clay but sometimes of stone were found
      at the Yarmukian Pottery Neolithic sites of Sha'ar HaGolan and Munhata (first
      half of the 8(th) millennium BP) in the Jordan Valley. Similar objects have been
      reported from other Near Eastern Pottery Neolithic sites. Most scholars have
      interpreted them as cultic objects in the shape of phalli, while others have
      referred to them in more general terms as "clay pestles," "clay rods," and
      "cylindrical clay objects." Re-examination of these artifacts leads us to present
      a new interpretation of their function and to suggest a reconstruction of their
      technology and mode of use. We suggest that these objects were components of fire
      drills and consider them the earliest evidence of a complex technology of fire
      ignition, which incorporates the cylindrical objects in the role of matches.

PMID- 22870305
TI  - Variation in mycorrhizal associations with tulasnelloid fungi among populations
      of five Dactylorhiza species.
AB  - BACKGROUND: Orchid species rely on mycorrhizal symbioses with fungi to complete
      their life cycle. Although there is mounting evidence that orchids can associate
      with several fungi from different clades or families, less is known about the
      actual geographic distribution of these fungi and how they are distributed across
      different orchid species within a genus. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated among-population variation in mycorrhizal associations in five
      species of the genus Dactylorhiza (D. fuchsii, D. incarnata, D. maculata, D.
      majalis and D. praetermissa) using culture-independent detection and
      identification techniques enabling simultaneous detection of multiple fungi in a
      single individual. Mycorrhizal specificity, determined as the number of fungal
      operational taxonomic units (OTUs), and phylogenetic diversity of fungi were
      compared between species, whereas discriminant analysis was used to compare
      mycorrhizal spectra across populations and species. Based on a 95% cut-off value
      in internal transcribed spacer (ITS) sequence similarity, a total of ten OTUs was
      identified belonging to three different clades within the Tulasnellaceae. Most
      OTUs were found in two or more Dactylorhiza species, and some of them were common
      and widespread, occurring in more than 50% of all sampled populations. Each
      orchid species associated with at least five different OTUs, whereas most
      individuals also associated with two or more fungal OTUs at the same time.
      Phylogenetic diversity, corrected for species richness, was not significantly
      different between species, confirming the generality of the observed orchid
      mycorrhizal associations. CONCLUSIONS/SIGNIFICANCE: We found that the
      investigated species of the genus Dactylorhiza associated with a wide range of
      fungal OTUs from the Tulasnellaceae, some of which were widespread and common.
      These findings challenge the idea that orchid rarity is related to mycorrhizal
      specificity and fungal distribution.

PMID- 22870307
TI  - Tubulin acetylation alone does not affect kinesin-1 velocity and run length in
      vitro.
AB  - Kinesin-1 plays a major role in anterograde transport of intracellular cargo
      along microtubules. Currently, there is an ongoing debate of whether alpha
      tubulin K40 acetylation directly enhances the velocity of kinesin-1 and its
      affinity to the microtubule track. We compared motor motility on microtubules
      reconstituted from acetylated and deacetylated tubulin. For both, single- and
      multi-motor in vitro motility assays, we demonstrate that tubulin acetylation
      alone does not affect kinesin-1 velocity and run length.

PMID- 22870308
TI  - Discovery of the corallivorous polyclad flatworm, Amakusaplana acroporae, on the
      Great Barrier Reef, Australia--the first report from the wild.
AB  - The role of corallivory is becoming increasingly recognised as an important
      factor in coral health at a time when coral reefs around the world face a number
      of other stressors. The polyclad flatworm, Amakusaplana acroporae, is a voracious
      predator of Indo-Pacific acroporid corals in captivity, and its inadvertent
      introduction into aquaria has lead to the death of entire coral colonies. While
      this flatworm has been a pest to the coral aquaculture community for over a
      decade, it has only been found in aquaria and has never been described from the
      wild. Understanding its biology and ecology in its natural environment is crucial
      for identifying viable biological controls for more successful rearing of
      Acropora colonies in aquaria, and for our understanding of what biotic
      interactions are important to coral growth and fitness on reefs. Using
      morphological, histological and molecular techniques we determine that a polyclad
      found on Acropora valida from Lizard Island, Australia is A. acroporae. The
      presence of extracellular Symbiodinium in the gut and parenchyma and spirocysts
      in the gut indicates that it is a corallivore in the wild. The examination of a
      size-range of individuals shows maturation of the sexual apparatus and increases
      in the number of eyes with increased body length. Conservative estimates of
      abundance show that A. acroporae occurred on 7 of the 10 coral colonies
      collected, with an average of 2.6+/-0.65 (mean +/-SE) animals per colony. This
      represents the first report of A. acroporae in the wild, and sets the stage for
      future studies of A. acroporae ecology and life history in its natural habitat.

PMID- 22870309
TI  - Differential expression of carotenogenic genes, associated changes on astaxanthin
      production and photosynthesis features induced by JA in H. pluvialis.
AB  - Haematococcus pluvialis is an organism that under certain conditions can produce
      astaxanthin, an economically important carotenoid. In this study, the
      transcriptional expression patterns of eight carotenogenic genes of H. pluvialis
      in response to jasmonic acid (JA) were evaluated using real-time PCR. Astaxanthin
      accumulation action and photosynthesis flourescence were monitored at the same
      time. The results showed all eight genes exhibited higher transcriptional
      expression significantly under JA treatments. JA25 (25 mg/L) induction had
      greater effect (>10-fold up-regulation) on the transcriptional expression of pds,
      crtR-B and lyc than on ipi-1, ipi-2, psy, bkt2, and crtO. JA50 (50 mg/L)
      treatment had greater impact on the transcriptional expression of ipi-1, ipi-2,
      psy, crtR-B and crtO than on pds, lyc and bkt2. Astaxanthin biosynthesis in the
      presence of JA appeared to be up-regulated mainly by psy, pds, crtR-B, lyc, bkt2
      and crtO at the transcriptional level and ipi-1, ipi-2 at both transcriptional
      and post-transcriptional levels. Under JA induction, the photosynthetic
      efficiency [Y (II)] and the maximum quantum efficiency of PS II (Fv/Fm) decreased
      significantly, but the non-photochemical quenching of chlorophyll fluorescence
      (NPQ) increased drastically with the accumulation of astaxanthin.

PMID- 22870310
TI  - Simultaneous detection and identification of enteric viruses by PCR-mass assay.
AB  - Simultaneous detection of enteric viruses that cause similar symptoms (e.g. hand,
      foot and mouth disease) is essential to the prevention of outbreaks and control
      of infections. In this study, a novel PCR-Mass assay combining multiplex
      polymerase chain reaction (PCR) with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) was developed and used for
      simultaneous detection of eight distinct human enteric viruses. Enteric viral
      isolates and standard viral RNAs were examined to determine the sensitivity and
      specificity of the PCR-Mass assay. Clinical performance was evaluated with a
      total of 101 clinical specimens from patients suspected of having hand, foot and
      mouth disease (HFMD). The results were compared to those of previous analyses
      using real-time RT-PCR. The identification of specific viruses and clinical
      specimens shows that the PCR-Mass assay performed as well as or better than
      standard methods with respect to indicating the presence of multiplex pathogens
      in a single specimen.

PMID- 22870311
TI  - Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and
      proliferation in normal lung cells.
AB  - BACKGROUND: Gremlin, a member of the Dan family of BMP antagonists, is a
      glycosylated extracellular protein. Previously Gremlin has been shown to play a
      role in dorsal-ventral patterning, in tissue remodeling, and recently in
      angiogenesis. Evidence has previously been presented showing both over- and under
      expression of Gremlin in different tumor tissues. Here, we sought to quantify
      expression of Gremlin in cancers of the lung and performed in vitro experiments
      to check whether Gremlin promotes cell growth and proliferation.
      METHODOLOGY/PRINCIPAL FINDINGS: Expression of Gremlin in 161 matched tumor and
      normal lung cancer specimens is quantified by quantitative real-time PCR and
      protein level is measured by immunohistochemistry. GREM1 was transfected into
      lung fibroblast and epithelial cell lines to assess the impact of overexpression
      of Gremlin in vitro. RESULTS: Lung adenocarcinoma but not squamous cell carcinoma
      shows a significant increase in Gremlin expression by mRNA and protein level.
      Lung fibroblast and epithelial cell lines transfected with GREM1 show
      significantly increased cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our data
      suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could
      hold promise as a new diagnostic marker or potential therapeutic target in lung
      AD or general thoracic malignancies.

PMID- 22870313
TI  - An investigation into the kinetics and mechanism of the removal of cyanobacteria
      by extract of Ephedra equisetina root.
AB  - An aqueous extract of Ephedra equisetina root was found to induce cyanobacterial
      cell death. The extract displayed no negative effects on the fish populations but
      instead, improved the habitat conditions for the growth of macrophytes,
      zooplankton and bacteria because the inhibiting effects of the extracts on
      cyanobacteria helped clear up the water column. The removal kinetics of
      cyanobacteria by E. equisetina extract appears to be a first order process with
      the rate constant being extract-dose-dependent. Compounds including the
      flavonoids found in E. equisetina root kill the cyanobacteria in vitro at a dose
      of 5.0 ug extract per 100 mL water or above. The extract constituents act to
      disrupt the thylakoid membrane, interrupt the electronic transport, decrease the
      effective quantum yield, and eventually lead to the failure of photosynthesis in
      Microcystis aeruginosa. This study presents an easily-deployed, natural and
      promising approach for controlling cyanobacterial blooms as an emergency measure,
      and also provides insight into the dynamics and mechanism of the extract
      consisting of multiple compounds synergistically removing algae.

PMID- 22870312
TI  - Leptospiral hemolysins induce proinflammatory cytokines through Toll-like
      receptor 2-and 4-mediated JNK and NF-kappaB signaling pathways.
AB  - BACKGROUND: Infection with pathogenic Leptospira species causes serious systemic
      inflammation in patients. Although a few leptospiral proinflammatory molecules
      have been identified, Leptospira likely encodes other unidentified strong
      inflammation stimulators. The pathogenic L. interrogans genome encodes numerous
      putative hemolysin genes. Since hemolysins from other bacteria can cause
      inflammatory reactions, we hypothesized that leptospiral hemolysins may function
      as proinflammatory stimulators that contribute to the strong inflammation
      associated with Leptospira infection. METHODOLOGY/PRINCIPAL FINDINGS: We first
      used cytokine protein microarrays for systematic analysis of serum cytokine
      profiles in leptospirosis patients and leptospire-infected mice. We found that IL
      1beta, IL-6 and TNF-alpha were the main proinflammatory cytokines in the sera of
      both the patients and the mice. We then analyzed eight putative hemolysins in L.
      interrogans strain Lai. The results showed that five of them, Sph1, Sph2, Sph3,
      HlpA and TlyA were secreted and had hemolytic activity. More importantly, these
      five hemolysins induced the strong production of IL-1beta, IL-6 and TNF-alpha in
      human and mouse macrophages (although a bit lower in the latter). Furthermore,
      blockade of TLR2 or TLR4 with either antibodies or inhibitors of the NF-kappaB or
      JNK signaling pathways significantly reduced the production of hemolysin-induced
      IL-1beta, IL-6 and TNF-alpha. Macrophages isolated from TLR2-, TLR4-or double
      TLR2-and 4-deficient mice also confirmed that the leptospiral hemolysins that
      induce proinflammatory cytokines are both TLR2-and TLR4-dependent.
      CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that L. interrogans secretes
      many hemolysins that function as powerful inducers of proinflammatory cytokines
      through both TLR2-and TLR4-dependent JNK and NF-kappaB pathways.

PMID- 22870314
TI  - Proteome analysis of the UVB-resistant marine bacterium Photobacterium angustum
      S14.
AB  - The proteome of the marine bacterium Photobacterium angustum S14 was exposed to
      UVB and analyzed by the implementation of both the post-digest ICPL labeling
      method and 2D-DIGE technique using exponentially growing cells. A total of 40 and
      23 proteins were quantified in all replicates using either the ICPL or 2D-DIGE
      methods, respectively. By combining both datasets from 8 biological replicates (4
      biological replicates for each proteomics technique), 55 proteins were found to
      respond significantly to UVB radiation in P. angustum. A total of 8 UVB
      biomarkers of P. angustum were quantified in all replicates using both methods.
      Among them, the protein found to present the highest increase in abundance
      (almost a 3-fold change) was RecA, which is known to play a crucial role in the
      so-called recombinational repair process. We also observed a high number of
      antioxidants, transport proteins, metabolism-related proteins,
      transcription/translation regulators, chaperonins and proteases. We also discuss
      and compare the UVB response and global protein expression profiles obtained for
      two different marine bacteria with trophic lifestyles: the copiotroph P. angustum
      and oligotroph Sphingopyxis alaskensis.

PMID- 22870315
TI  - High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit
      model of embolic stroke.
AB  - It is estimated that only 2-6% of patients receive thrombolytic therapy for acute
      ischemic stroke suggesting that alternative therapies are necessary. In this
      study, we investigate the potential for high intensity focused ultrasound (HIFU)
      to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots
      were injected into the middle cerebral artery (MCA) of New Zealand White rabbits,
      through the internal carotid artery and blockages were confirmed by angiography.
      MRI was used to localize the iron-loaded clot and target the HIFU beam for
      treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20
      s duration) were applied to initiate thrombolysis. Repeat angiograms and
      histology were used to assess reperfusion and vessel damage. Using 275 W of
      acoustic power, there was no evidence of reperfusion in post-treatment angiograms
      of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was
      applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the
      last group of animals, acoustic power was further increased to 550 W, which led
      to the reperfusion in 5 of 7 (~70%) animals tested. Histological analysis
      confirmed that the sonicated vessels remained intact after HIFU treatment.
      Hemorrhage was detected outside of the sonication site, likely due to the
      proximity of the target vessel with the base of the rabbit skull. These results
      demonstrate the feasibility of using HIFU, as a stand-alone method, to cause
      effective thrombolysis without immediate damage to the targeted vessels. HIFU,
      combined with imaging modalities used to identify and assess stroke patients,
      could dramatically reduce the time to achieve flow restoration in patients
      thereby significantly increasing the number of patients which benefit from
      thrombolysis treatments.

PMID- 22870316
TI  - Involvement of calpain/p35-p25/Cdk5/NMDAR signaling pathway in glutamate-induced
      neurotoxicity in cultured rat retinal neurons.
AB  - We investigated possible involvement of a calpain/p35-p25/cyclin-dependent kinase
      5 (Cdk5) signaling pathway in modifying NMDA receptors (NMDARs) in glutamate
      induced injury of cultured rat retinal neurons. Glutamate treatment decreased
      cell viability and induced cell apoptosis, which was accompanied by an increase
      in Cdk5 and p-Cdk5(T15) protein levels. The Cdk5 inhibitor roscovitine rescued
      the cell viability and inhibited the cell apoptosis. In addition, the protein
      levels of both calpain 2 and calpain-specific alpha-spectrin breakdown products
      (SBDPs), which are both Ca(2+)-dependent, were elevated in glutamate-induced cell
      injury. The protein levels of Cdk5, p-Cdk5(T15), calpain 2 and SBDPs tended to
      decline with glutamate treatments of more than 9 h. Furthermore, the elevation of
      SBDPs was attenuated by either D-APV, a NMDAR antagonist, or CNQX, a non-NMDAR
      antagonist, but was hardly changed by the inhibitors of intracellular calcium
      stores dantrolene and xestospongin. Moreover, the Cdk5 co-activator p35 was
      significantly up-regulated, whereas its cleaved product p25 expression showed a
      transient increase. Glutamate treatment for less than 9 h also considerably
      enhanced the ratio of the Cdk5-phosphorylated NMDAR subunit NR2A at Ser1232 site
      (p-NR2A(S1232)) and NR2A (p-NR2A(S1232)/NR2A), and caused a translocation of p
      NR2A(S1232) from the cytosol to the plasma membrane. The enhanced p-NR2A(S1232)
      was inhibited by roscovitine, but augmented by over-expression of Cdk5. Calcium
      imaging experiments further showed that intracellular Ca(2+) concentrations
      ([Ca(2+)](i)) of retinal cells were steadily increased following glutamate
      treatments of 2 h, 6 h and 9 h. All these results suggest that the activation of
      the calpain/p35-p25/Cdk5 signaling pathway may contribute to glutamate
      neurotoxicity in the retina by up-regulating p-NR2A(S1232) expression.

PMID- 22870317
TI  - Depressive symptoms and cortisol rhythmicity predict survival in patients with
      renal cell carcinoma: role of inflammatory signaling.
AB  - PURPOSE: Evidence has supported the association between psychological factors and
      cancer biology; however, findings are equivocal on the role of psychosocial
      factors in cancer progression. This study generates a hypothesis of mechanistic
      variables by examining the clinical effects of psychosocial factors and cortisol
      dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines
      associated activation of transcription control pathways. METHODS: Patients with
      metastatic RCC (n = 217) were prospectively enrolled in this study. Patients
      completed questionnaires (Centers for Epidemiologic Studies-Depression; SF-36
      Health Status Survey; Duke Social Support Index; Coping Operations Preference
      Enquiry; organized and non-organized religious activity; and intrinsic
      religiosity), and provided blood and saliva samples. Cortisol levels and whole
      genome transcriptional profiling were assessed to identify potential alterations
      in circadian rhythms and genomic pathways. RESULTS: Separate Cox regression
      models, controlling for disease risk category, revealed that CES-D scores (p =
      0.05, HR = 1.5, 95% CI for HR: 1.00-2.23) and cortisol slope (p = 0.002; HR =
      1.9; 95%CI for HR: 1.27-2.97) were significantly associated with decreased
      survival. Only cortisol slope and risk category remained significant in the
      complete model. Functional genomic analyses linked depressive symptoms to
      increased expression of pro-inflammatory and pro-metastatic genes in circulating
      leukocytes. 116 transcripts were found to be upregulated by an average of 50% or
      more in high CES-D patients, and 57 transcripts downregulated by at least 50%.
      These changes were also found in the tumor in a subset of patients. CONCLUSION:
      These findings identify depressive symptoms as a key predictor of survival in
      renal cell carcinoma patients with potential links to dysregulation of cortisol
      and inflammatory biology.

PMID- 22870318
TI  - Genetic deletion of NR3A accelerates glutamatergic synapse maturation.
AB  - Glutamatergic synapse maturation is critically dependent upon activation of NMDA
      type glutamate receptors (NMDARs); however, the contributions of NR3A subunit
      containing NMDARs to this process have only begun to be considered. Here we
      characterized the expression of NR3A in the developing mouse forebrain and
      examined the consequences of NR3A deletion on excitatory synapse maturation. We
      found that NR3A is expressed in many subcellular compartments, and during early
      development, NR3A subunits are particularly concentrated in the postsynaptic
      density (PSD). NR3A levels dramatically decline with age and are no longer
      enriched at PSDs in juveniles and adults. Genetic deletion of NR3A accelerates
      glutamatergic synaptic transmission, as measured by AMPAR-mediated postsynaptic
      currents recorded in hippocampal CA1. Consistent with the functional
      observations, we observed that the deletion of NR3A accelerated the expression of
      the glutamate receptor subunits NR1, NR2A, and GluR1 in the PSD in postnatal day
      (P) 8 mice. These data support the idea that glutamate receptors concentrate at
      synapses earlier in NR3A-knockout (NR3A-KO) mice. The precocious maturation of
      both AMPAR function and glutamate receptor expression are transient in NR3A-KO
      mice, as AMPAR currents and glutamate receptor protein levels are similar in NR3A
      KO and wildtype mice by P16, an age when endogenous NR3A levels are normally
      declining. Taken together, our data support a model whereby NR3A negatively
      regulates the developmental stabilization of glutamate receptors involved in
      excitatory neurotransmission, synaptogenesis, and spine growth.

PMID- 22870319
TI  - Exposure to 1950-MHz TD-SCDMA electromagnetic fields affects the apoptosis of
      astrocytes via caspase-3-dependent pathway.
AB  - The usage of mobile phone increases globally. However, there is still a paucity
      of data about the impact of electromagnetic fields (EMF) on human health. This
      study investigated whether EMF radiation would alter the biology of glial cells
      and act as a tumor-promoting agent. We exposed rat astrocytes and C6 glioma cells
      to 1950-MHz TD-SCDMA for 12, 24 and 48 h respectively, and found that EMF
      exposure had differential effects on rat astroctyes and C6 glioma cells. A 48 h
      of exposure damaged the mitochondria and induced significant apoptosis of
      astrocytes. Moreover, caspase-3, a hallmark of apoptosis, was highlighted in
      astrocytes after 48 h of EMF exposure, accompanied by a significantly increased
      expression of bax and reduced level of bcl-2. The tumorigenicity assays
      demonstrated that astrocytes did not form tumors in both control and exposure
      groups. In contrast, the unexposed and exposed C6 glioma cells show no
      significant differences in both biological feature and tumor formation ability.
      Therefore, our results implied that exposure to the EMF of 1950-MHz TD-SCDMA may
      not promote the tumor formation, but continuous exposure damaged the mitochondria
      of astrocytes and induce apoptosis through a caspase-3-dependent pathway with the
      involvement of bax and bcl-2.

PMID- 22870320
TI  - Optimized PCR conditions and increased shRNA fold representation improve
      reproducibility of pooled shRNA screens.
AB  - RNAi screening using pooled shRNA libraries is a valuable tool for identifying
      genetic regulators of biological processes. However, for a successful pooled
      shRNA screen, it is imperative to thoroughly optimize experimental conditions to
      obtain reproducible data. Here we performed viability screens with a library of
      ~10,000 shRNAs at two different fold representations (100- and 500-fold at
      transduction) and report the reproducibility of shRNA abundance changes between
      screening replicates determined by microarray and next generation sequencing
      analyses. We show that the technical reproducibility between PCR replicates from
      a pooled screen can be drastically improved by ensuring that PCR amplification
      steps are kept within the exponential phase and by using an amount of genomic DNA
      input in the reaction that maintains the average template copies per shRNA used
      during library transduction. Using these optimized PCR conditions, we then show
      that higher reproducibility of biological replicates is obtained by both
      microarray and next generation sequencing when screening with higher average
      shRNA fold representation. shRNAs that change abundance reproducibly in
      biological replicates (primary hits) are identified from screens performed with
      both 100- and 500-fold shRNA representation, however a higher percentage of
      primary hit overlap between screening replicates is obtained from 500-fold shRNA
      representation screens. While strong hits with larger changes in relative
      abundance were generally identified in both screens, hits with smaller changes
      were identified only in the screens performed with the higher shRNA fold
      representation at transduction.

PMID- 22870321
TI  - Effects of chemosignals from sad tears and postprandial plasma on appetite and
      food intake in humans.
AB  - Chemosignals from human body fluids may modulate biological functions in humans.
      The objective of this study was to examine whether chemosignals from human sad
      tears and postprandial plasma modulate appetite. We obtained fasting and
      postprandial plasma from male participants and sad tears and saline, which was
      trickled below the eyelids, from female volunteers. These samples were then
      randomly distributed to male participants to sniff with a band-aid containing 100
      ul of each fluid on four consecutive days in a double-blind fashion. We checked
      appetite by a visual analogue scale (VAS) and food intake by measuring the
      consumption of a test meal. In addition, the serum levels of total testosterone
      and LH were measured. Twenty men (mean age 26.3+/-4.6 years) were enrolled in
      this study. They could not discriminate between the smell of fasting and
      postprandial plasma and the smell of sad tears and trickled saline. Appetite and
      the amount of food intake were not different between the groups. Although the VAS
      ratings of appetite correlated with the food intake upon sniffing fasting plasma,
      postprandial plasma, and trickled saline, there was no such correlation upon
      sniffing sad tears. In addition, the decrease in serum testosterone levels from
      the baseline was greater with sad tears than with the trickled saline (-28.6+/
      3.3% vs. -14.0+/-5.2%; P = 0.019). These data suggest that chemosignals from
      human sad tears and postprandial plasma do not appear to reduce appetite and food
      intake. However, further studies are necessary to examine whether sad tears may
      alter the appetite-eating behavior relation.

PMID- 22870322
TI  - An ORMOSIL-containing orthodontic acrylic resin with concomitant improvements in
      antimicrobial and fracture toughness properties.
AB  - Global increase in patients seeking orthodontic treatment creates a demand for
      the use of acrylic resins in removable appliances and retainers. Orthodontic
      removable appliance wearers have a higher risk of oral infections that are caused
      by the formation of bacterial and fungal biofilms on the appliance surface. Here,
      we present the synthetic route for an antibacterial and antifungal organically
      modified silicate (ORMOSIL) that has multiple methacryloloxy functionalities
      attached to a siloxane backbone (quaternary ammonium methacryloxy silicate, or
      QAMS). By dissolving the water-insoluble, rubbery ORMOSIL in methyl methacrylate,
      QAMS may be copolymerized with polymethyl methacrylate, and covalently
      incorporated in the pressure-processed acrylic resin. The latter demonstrated a
      predominantly contact-killing effect on Streptococcus mutans ATCC 36558 and
      Actinomyces naselundii ATCC 12104 biofilms, while inhibiting adhesion of Candida
      albicans ATCC 90028 on the acrylic surface. Apart from its favorable
      antimicrobial activities, QAMS-containing acrylic resins exhibited decreased
      water wettability and improved toughness, without adversely affecting the
      flexural strength and modulus, water sorption and solubility, when compared with
      QAMS-free acrylic resin. The covalently bound, antimicrobial orthodontic acrylic
      resin with improved toughness represents advancement over other experimental
      antimicrobial acrylic resin formulations, in its potential to simultaneously
      prevent oral infections during appliance wear, and improve the fracture
      resistance of those appliances.

PMID- 22870323
TI  - Functional and morphological cardiac magnetic resonance imaging of mice using a
      cryogenic quadrature radiofrequency coil.
AB  - Cardiac morphology and function assessment by magnetic resonance imaging is of
      increasing interest for a variety of mouse models in pre-clinical cardiac
      research, such as myocardial infarction models or myocardial injury/remodeling in
      genetically or pharmacologically induced hypertension. Signal-to-noise ratio
      (SNR) constraints, however, limit image quality and blood myocardium delineation,
      which crucially depend on high spatial resolution. Significant gains in SNR with
      a cryogenically cooled RF probe have been shown for mouse brain MRI, yet the
      potential of applying cryogenic RF coils for cardiac MR (CMR) in mice is, as of
      yet, untapped. This study examines the feasibility and potential benefits of CMR
      in mice employing a 400 MHz cryogenic RF surface coil, compared with a
      conventional mouse heart coil array operating at room temperature. The cryogenic
      RF coil affords SNR gains of 3.0 to 5.0 versus the conventional approach and
      hence enables an enhanced spatial resolution. This markedly improved image
      quality--by better deliniation of myocardial borders and enhanced depiction of
      papillary muscles and trabeculae--and facilitated a more accurate cardiac chamber
      quantification, due to reduced intraobserver variability. In summary the use of a
      cryogenically cooled RF probe represents a valuable means of enhancing the
      capabilities of CMR of mice.

PMID- 22870324
TI  - A key role for the endothelium in NOD1 mediated vascular inflammation: comparison
      to TLR4 responses.
AB  - Understanding the mechanisms by which pathogens induce vascular inflammation and
      dysfunction may reveal novel therapeutic targets in sepsis and related
      conditions. The intracellular receptor NOD1 recognises peptidoglycan which
      features in the cell wall of gram negative and some gram positive bacteria. NOD1
      engagement generates an inflammatory response via activation of NFkappaB and MAPK
      pathways. We have previously shown that stimulation of NOD1 directly activates
      blood vessels and causes experimental shock in vivo. In this study we have used
      an ex vivo vessel-organ culture model to characterise the relative contribution
      of the endothelium in the response of blood vessels to NOD1 agonists. In addition
      we present the novel finding that NOD1 directly activates human blood vessels.
      Using human cultured cells we confirm that endothelial cells respond more avidly
      to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to
      pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in
      human endothelial cells, focussing on TAK1, NFkappaB and p38 MAPK. In addition we
      profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1
      ligand induced inflammatory signalling in the vasculature. This paper is the
      first to demonstrate activation of whole human artery by NOD1 stimulation and the
      relative importance of the endothelium in the sensing of NOD1 ligands by vessels.
      This data supports the potential utility of NOD1 and RIP2 as therapeutic targets
      in human disease where vascular inflammation is a clinical feature, such as in
      sepsis and septic shock.

PMID- 22870325
TI  - miRSystem: an integrated system for characterizing enriched functions and
      pathways of microRNA targets.
AB  - BACKGROUND: Many prediction tools for microRNA (miRNA) targets have been
      developed, but inconsistent predictions were observed across multiple algorithms,
      which can make further analysis difficult. Moreover, the nomenclature of human
      miRNAs changes rapidly. To address these issues, we developed a web-based system,
      miRSystem, for converting queried miRNAs to the latest annotation and predicting
      the function of miRNA by integrating miRNA target gene prediction and
      function/pathway analyses. RESULTS: First, queried miRNA IDs were converted to
      the latest annotated version to prevent potential conflicts resulting from
      multiple aliases. Next, by combining seven algorithms and two validated
      databases, potential gene targets of miRNAs and their functions were predicted
      based on the consistency across independent algorithms and observed/expected
      ratios. Lastly, five pathway databases were included to characterize the enriched
      pathways of target genes through bootstrap approaches. Based on the enriched
      pathways of target genes, the functions of queried miRNAs could be predicted.
      CONCLUSIONS: MiRSystem is a user-friendly tool for predicting the target genes
      and their associated pathways for many miRNAs simultaneously. The web server and
      the documentation are freely available at http://mirsystem.cgm.ntu.edu.tw/.

PMID- 22870326
TI  - The effect of gonadotropin on glucose transport and apoptosis in rat ovary.
AB  - Although the effects of Gonadotropin on ovarian physiology have been known for
      many decades, its action on glucose uptake in the rat ovary remained poorly
      understood. Evidence also suggests that glucose uptake is mediated by a number of
      glucose transporter proteins (Glut). Therefore, we examined the rat ovary for the
      presence of Glut1-4 and blood glucose level after eCG (equine chorionic
      gonadotropin) and anti-eCG antiserum treatment. All of the glucose transports
      were present in the ovarian oocyte, granulosa cells and theca cells in different
      stage follicles. The expression of Glut in ovary was up-regulated by eCG,
      however, anti-eCG antiserum reversed eCG action. Western blot analysis also
      demonstrated the content of Glut1 was higher in eCG treatment group compared with
      anti-eCG antiserum and control group. The same tendency was shown in other glut
      isoforms. Moreover, there were no significant difference between the anti-eCG
      antiserum and control group. In additional, the level of serum glucose in eCG
      treatment group was significantly higher than others, which is similar with glut
      expression pattern. High glucose level in blood is correlated with increased
      expression of glucose transporter proteins in rat ovary. Meanwhile, anti-eCG
      antiserum increased granulosa cell apoptosis in antral follicle compared with
      those in eCG group. Our observations provide potential explanation for the
      effects of Glut on follicular development in rat ovary and a role for eCG in the
      regulation of ovarian glucose uptake.

PMID- 22870327
TI  - Interannual variability of cyanobacterial blooms in Lake Erie.
AB  - After a 20-year absence, severe cyanobacterial blooms have returned to Lake Erie
      in the last decade, in spite of negligible change in the annual load of total
      phosphorus (TP). Medium-spectral Resolution Imaging Spectrometer (MERIS) imagery
      was used to quantify intensity of the cyanobacterial bloom for each year from
      2002 to 2011. The blooms peaked in August or later, yet correlate to discharge
      (Q) and TP loads only for March through June. The influence of the spring TP load
      appears to have started in the late 1990 s, after Dreissenid mussels colonized
      the lake, as hindcasts prior to 1998 are inconsistent with the observed blooms.
      The total spring Q or TP load appears sufficient to predict bloom magnitude,
      permitting a seasonal forecast prior to the start of the bloom.

PMID- 22870328
TI  - Affective responses by adults with autism are reduced to social images but
      elevated to images related to circumscribed interests.
AB  - Individuals with autism spectrum disorders (ASD) demonstrate increased visual
      attention and elevated brain reward circuitry responses to images related to
      circumscribed interests (CI), suggesting that a heightened affective response to
      CI may underlie their disproportionate salience and reward value in ASD. To
      determine if individuals with ASD differ from typically developing (TD) adults in
      their subjective emotional experience of CI object images, non-CI object images
      and social images, 213 TD adults and 56 adults with ASD provided arousal ratings
      (sensation of being energized varying along a dimension from calm to excited) and
      valence ratings (emotionality varying along dimension of approach to withdrawal)
      for a series of 114 images derived from previous research on CI. The groups did
      not differ on arousal ratings for any image type, but ASD adults provided higher
      valence ratings than TD adults for CI-related images, and lower valence ratings
      for social images. Even after co-varying the effects of sex, the ASD group, but
      not the TD group, gave higher valence ratings to CI images than social images.
      These findings provide additional evidence that ASD is characterized by a
      preference for certain categories of non-social objects and a reduced preference
      for social stimuli, and support the dissemination of this image set for examining
      aspects of the circumscribed interest phenotype in ASD.

PMID- 22870329
TI  - SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into
      CD4+ FoxP3+ T regulatory cells by production of IFN-gamma.
AB  - Tumors convert conventional CD4(+) T cells into induced CD4(+)CD25(+)FoxP3(+) T
      regulatory (iTreg) cells that serve as an effective means of immune evasion.
      Therefore, the blockade of conventional CD4(+) T cell conversion into iTreg cells
      represents an attractive target for improving the efficacy of various
      immunotherapeutic approaches. Using a novel form of 4-1BBL molecule, SA-4-1BBL,
      we previously demonstrated that costimulation via 4-1BB receptor renders both
      CD4(+)and CD8(+) T effector (Teff) cells refractory to inhibition by Treg cells
      and increased intratumoral Teff/Treg cell ratio that correlated with therapeutic
      efficacy in various preclinical tumor models. Building on these studies, we
      herein show for the first time, to our knowledge, that signaling through 4-1BB
      inhibits antigen- and TGF-beta-driven conversion of naive CD4(+)FoxP3(-) T cells
      into iTreg cells via stimulation of IFN-gamma production by CD4(+)FoxP3(-) T
      cells. Importantly, treatment with SA-4-1BBL blocked the conversion of
      CD4(+)FoxP3(-) T cells into Treg cells by EG.7 tumors. Taken together with our
      previous studies, these results show that 4-1BB signaling negatively modulate
      Treg cells by two distinct mechanisms: i) inhibiting the conversion of
      CD4(+)FoxP3(-) T cells into iTreg cells and ii) endowing Teff cells refractory to
      inhibition by Treg cells. Given the dominant role of Treg cells in tumor immune
      evasion mechanisms, 4-1BB signaling represents an attractive target for favorably
      tipping the Teff:Treg balance toward Teff cells with important implications for
      cancer immunotherapy.

PMID- 22870330
TI  - Proteomic profiling of a mouse model for ovarian granulosa cell tumor identifies
      VCP as a highly sensitive serum tumor marker in several human cancers.
AB  - The initial aim of this study was to identify novel serum diagnostic markers for
      the human ovarian granulosa cell tumor (GCT), a tumor that represents up to 5% of
      all ovarian cancers. To circumvent the paucity of human tissues available for
      analyses, we used the Ctnnb1(tm1Mmt/+);Pten(tm1Hwu/tmiHwu);Amhr2(tm3(cre)Bhr/+)
      transgenic mouse model, which features the constitutive activation of CTNNB1
      signaling combined with the loss of Pten in granulosa cells and develops GCTs
      that mimic aggressive forms of the human disease. Proteomic profiling by mass
      spectrometry showed that vinculin, enolase 1, several heat shock proteins, and
      valosin containing protein (VCP) were more abundantly secreted by cultured mouse
      GCT cells compared to primary cultured GC. Among these proteins, only VCP was
      present in significantly increased levels in the preoperative serum of GCT cancer
      patients compared to normal subjects. To determine the specificity of VCP, serum
      levels were also measured in ovarian carcinoma, non-Hodgkin's lymphoma and
      breast, colon, pancreatic, lung, and prostate cancer patients. Increased serum
      VCP levels were observed in the majority of cancer cases, with the exception of
      patients with lung or prostate cancer. Moreover, serum VCP levels were increased
      in some GCT, ovarian carcinoma, breast cancer, and colon cancer patients who did
      not otherwise display increased levels of widely used serum tumor markers for
      their cancer type (e.g. inhibin A, inhibin B, CA125, CEA, or CA15.3). These
      results demonstrate the potential use of VCP as highly sensitive serum marker for
      GCT as well as several other human cancers.

PMID- 22870331
TI  - Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS
      and TRIF.
AB  - Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The
      finding that CHV is genetically the virus most closely related to hepatitis C
      virus (HCV) has raised the question of whether HCV might have evolved as the
      result of close contact between dogs and/or horses and humans. The aim of this
      study was to investigate whether the NS3/4A serine protease of CHV specifically
      cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1
      receptor domain-containing adaptor inducing interferon-beta (TRIF). The
      proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda
      genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into
      the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing
      these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000
      fold more efficiently than in cells expressing a CHV protease variant carrying
      the inactivating substitution S139A. Comparable results were obtained when
      several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that
      CHV can disrupt the human innate antiviral defense signaling pathway and suggests
      a possible evolutionary relationship between CHV and HCV.

PMID- 22870332
TI  - A non-destructive culturing and cell sorting method for cardiomyocytes and
      neurons using a double alginate layer.
AB  - A non-destructive method of collecting cultured cells after identifying their in
      situ functional characteristics is proposed. In this method, cells are cultivated
      on an alginate layer in a culture dish and released by spot application of a
      calcium chelate buffer that locally melts the alginate layer and enables the
      collection of cultured cells at the single-cell level. Primary hippocampal
      neurons, beating human embryonic stem (hES) cell-derived cardiomyocytes, and
      beating hES cell-derived cardiomyocyte clusters cultivated on an alginate layer
      were successfully released and collected with a micropipette. The collected cells
      were recultured while maintaining their physiological function, including
      beating, and elongated neurites. These results suggest that the proposed method
      may eventually facilitate the transplantation of ES- or iPS-derived
      cardiomyocytes and neurons differentiated in culture.

PMID- 22870333
TI  - De novo sequencing and transcriptome analysis of the central nervous system of
      mollusc Lymnaea stagnalis by deep RNA sequencing.
AB  - The pond snail Lymnaea stagnalis is among several mollusc species that have been
      well investigated due to the simplicity of their nervous systems and large
      identifiable neurons. Nonetheless, despite the continued attention given to the
      physiological characteristics of its nervous system, the genetic information of
      the Lymnaea central nervous system (CNS) has not yet been fully explored. The
      absence of genetic information is a large disadvantage for transcriptome
      sequencing because it makes transcriptome assembly difficult. We here performed
      transcriptome sequencing for Lymnaea CNS using an Illumina Genome Analyzer IIx
      platform and obtained 81.9 M of 100 base pair (bp) single end reads. For de novo
      assembly, five programs were used: ABySS, Velvet, OASES, Trinity and Rnnotator.
      Based on a comparison of the assemblies, we chose the Rnnotator dataset for the
      following blast searches and gene ontology analyses. The present dataset, 116,355
      contigs of Lymnaea transcriptome shotgun assembly (TSA), contained longer
      sequences and was much larger compared to the previously reported Lymnaea
      expression sequence tag (EST) established by classical Sanger sequencing. The TSA
      sequences were subjected to blast analyses against several protein databases and
      Aplysia EST data. The results demonstrated that about 20,000 sequences had
      significant similarity to the reported sequences using a cutoff value of 1e-6,
      and showed the lack of molluscan sequences in the public databases. The richness
      of the present TSA data allowed us to identify a large number of new transcripts
      in Lymnaea and molluscan species.

PMID- 22870334
TI  - Internal soft-tissue anatomy of Cambrian 'Orsten' arthropods as revealed by
      synchrotron X-ray tomographic microscopy.
AB  - The world-famous 'Orsten' Konservat-Lagerstatte has yielded detailed information
      about Cambrian arthropods and their morphology. Internal organs or soft tissues
      have, however, rarely been reported, an obvious palaeobiological drawback. In
      this study, we employed synchrotron radiation X-ray tomographic microscopy
      (SRXTM) to study microscopic 'Orsten' arthropods from the Cambrian of Sweden:
      Skara minuta and two phosphatocopine species, Hesslandona sp. and Hesslandona
      trituberculata. This exceptionally high-resolution technique reveals internal
      organs or soft tissues that allow detailed comparison with equivalent structures
      in extant crustaceans and functional inferences to be made. The S. minuta
      specimen shows the digestive system and muscles that extend to the extremities.
      The slanting anterior portion of the head and anterior position of the mouth with
      a straight oesophagus suggest a primarily brushing and scraping way of feeding.
      The prominent head appendage muscles indicate muscle strength and good capacity
      for food manipulation. In the phosphatocopines the bulbous labrum is one of the
      most prominent morphological structures of the body. All specimens analysed
      reveal pairs of muscle bundles within the labrum. Based on comparisons with
      extant crustacean relatives, these muscles would fulfil the function of moving
      the labrum up and down in order to open the buccal cavity. The results of this
      pilot study demonstrate that there is still much to be learned about the 'Orsten'
      taxa.

PMID- 22870335
TI  - DLA class II alleles and haplotypes are associated with risk for and protection
      from chronic hepatitis in the English Springer spaniel.
AB  - Chronic hepatitis (CH) is common in dogs in the United Kingdom. An increased
      prevalence of the disease is seen in the English Springer spaniel (ESS), and this
      breed suffer from a severe form with young to middle aged female dogs being
      predisposed. The disease shares histological features with those of human viral
      hepatitis, although the specific aetiological agent has not yet been identified.
      The aim of the current study was to investigate whether dog leucocyte antigen
      (DLA) class II alleles and haplotypes are associated with
      susceptibility/resistance to CH in the ESS. Sequence-based genotyping of the
      polymorphic exon 2 from DLA-DRB1, -DQA1 and -DQB1 class II loci were performed in
      66 ESSs with CH and 84 healthy controls. There was a significant difference in
      the distribution of the protective alleles DRB1*00501 (3.0% vs. 12.0%, odds ratio
      [OR] = 0.23, 95% confidence interval [CI] = 0.06-0.74) and DQB1*00501 (3.8% vs.
      12.0%, OR = 0.29, 95% CI = 0.09-0.85) between cases and controls. The haplotype
      DLA-DRB1*00501/DQA1*00301/DQB1*00501 was present in 11.9% of controls and 3.0% of
      cases and was significantly associated with protection against disease
      development (OR = 0.26, 95% CI = 0.08-0.80). There was a significant difference
      in the distribution of the risk alleles DRB1*00601 (14.4% vs. 6.5%, OR = 2.40,
      95% CI = 1.10-5.63) and DQB1*00701 (14.4% vs. 6.5%, OR = 2.40, 95% CI = 1.10
      5.63) between cases and controls. A risk haplotype (DLA
      DRB1*00601/DQA1*005011/DQB1*00701) was present in 14.4% of cases and 6.5% of
      controls and conferred an elevated risk of developing CH with an OR of 3.13 (95%
      CI = 1.20-8.26). These results demonstrate that DLA class II is significantly
      associated with risk and protection from developing CH in ESSs.

PMID- 22870336
TI  - Role of high-fat diet in stress response of Drosophila.
AB  - Obesity is associated with many diseases, one of the most common being
      obstructive sleep apnea (OSA), which in turn leads to blood gas disturbances,
      including intermittent hypoxia (IH). Obesity, OSA and IH are associated with
      metabolic changes, and while much mammalian work has been done, mechanisms
      underlying the response to IH, the role of obesity and the interaction of obesity
      and hypoxia remain unknown. As a model organism, Drosophila offers tremendous
      power to study a specific phenotype and, at a subsequent stage, to uncover and
      study fundamental mechanisms, given the conservation of molecular pathways.
      Herein, we characterize the phenotype of Drosophila on a high-fat diet in
      normoxia, IH and constant hypoxia (CH) using triglyceride and glucose levels,
      response to stress and lifespan. We found that female flies on a high-fat diet
      show increased triglyceride levels (p<0.001) and a shortened lifespan in
      normoxia, IH and CH. Furthermore, flies on a high-fat diet in normoxia and CH
      show diminished tolerance to stress, with decreased survival after exposure to
      extreme cold or anoxia (p<0.001). Of interest, IH seems to rescue this decreased
      cold tolerance, as flies on a high-fat diet almost completely recovered from cold
      stress following IH. We conclude that the cross talk between hypoxia and a high
      fat diet can be either deleterious or compensatory, depending on the nature of
      the hypoxic treatment.

PMID- 22870337
TI  - Chlamydia muridarum lung infection in infants alters hematopoietic cells to
      promote allergic airway disease in mice.
AB  - BACKGROUND: Viral and bacterial respiratory tract infections in early-life are
      linked to the development of allergic airway inflammation and asthma. However,
      the mechanisms involved are not well understood. We have previously shown that
      neonatal and infant, but not adult, chlamydial lung infections in mice
      permanently alter inflammatory phenotype and physiology to increase the severity
      of allergic airway disease by increasing lung interleukin (IL)-13 expression,
      mucus hyper-secretion and airway hyper-responsiveness. This occurred through
      different mechanisms with infection at different ages. Neonatal infection
      suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL
      13 release and induced permanent alterations in lung structure (i.e., increased
      the size of alveoli). Infant infection enhanced inflammatory responses but had no
      effect on lung structure. Here we investigated the role of hematopoietic cells in
      these processes using bone marrow chimera studies. METHODOLOGY/PRINCIPAL
      FINDINGS: Neonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old)
      mice were infected with C. muridarum. Nine weeks after infection bone marrow was
      collected and transferred into recipient age-matched irradiated naive mice.
      Allergic airway disease was induced (8 weeks after adoptive transfer) by
      sensitization and challenge with ovalbumin. Reconstitution of irradiated naive
      mice with bone marrow from mice infected as neonates resulted in the suppression
      of the hallmark features of allergic airway disease including mucus hyper
      secretion and airway hyper-responsiveness, which was associated with decreased IL
      13 levels in the lung. In stark contrast, reconstitution with bone marrow from
      mice infected as infants increased the severity of allergic airway disease by
      increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper
      secretion, airway hyper-responsiveness and IL-13 levels in the lung.
      Reconstitution with bone marrow from infected adult mice had no effects.
      CONCLUSIONS: These results suggest that an infant chlamydial lung infection
      results in long lasting alterations in hematopoietic cells that increases the
      severity of allergic airway disease in later-life.

PMID- 22870338
TI  - De novo transcriptome assembly and SNP discovery in the wing polymorphic salt
      marsh beetle Pogonus chalceus (Coleoptera, Carabidae).
AB  - BACKGROUND: The salt marsh beetle Pogonus chalceus represents a unique
      opportunity to understand and study the origin and evolution of dispersal
      polymorphisms as remarkable inter-population divergence in dispersal related
      traits (e.g. wing development, body size and metabolism) has been shown to
      persist in face of strong homogenizing gene flow. Sequencing and assembling the
      transcriptome of P. chalceus is a first step in developing large scale genetic
      information that will allow us to further study the recurrent phenotypic
      evolution in dispersal traits in these natural populations. METHODOLOGY/RESULTS:
      We used the Illumina HiSeq2000 to sequence 37 Gbases of the transcriptome and
      performed de novo transcriptome assembly with the Trinity short read assembler.
      This resulted in 65,766 contigs, clustering into 39,393 unique transcripts
      (unigenes). A subset of 12,987 show similarity (BLAST) to known proteins in the
      NCBI database and 7,589 are assigned Gene Ontology (GO). Using homology searches
      we identified all reported genes involved in wing development, juvenile- and
      ecdysteroid hormone pathways in Tribolium castaneum. About half (56.7%) of the
      unique assembled genes are shared among three life stages (third-instar larva,
      pupa, and imago). We identified 38,141 single nucleotide polymorphisms (SNPs) in
      these unigenes. Of these SNPs, 26,823 (70.3%) were found in a predicted open
      reading frame (ORF) and 6,998 (18.3%) were nonsynonymous. CONCLUSIONS: The
      assembled transcriptome and SNP data are essential genomic resources for further
      study of the developmental pathways, genetic mechanisms and metabolic
      consequences of adaptive divergence in dispersal power in natural populations.

PMID- 22870339
TI  - Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in
      mouse model.
AB  - Development and function of mesodiencephalic dopaminergic (mdDA) neurons has
      received a lot of scientific interest since these neurons are critically involved
      in neurological diseases as Parkinson and psychiatric diseases as schizophrenia,
      depression and attention deficit hyperactivity disorder (ADHD). The understanding
      of the molecular processes that lead to normal development and function of mdDA
      neurons has provided insight in the pathology and provided critical information
      on new treatment paradigms. In order to be able to study specific genetic
      ablation in mdDA neurons a new tools was developed that drives Cre-recombinase
      under the control of the Pitx3 locus. The Pitx3 gene is well known for its
      specific expression in mdDA neurons and is present at the onset of terminal
      differentiation. Analysis of newly generated Pitx3-Cre knock-in mice shows that
      Cre expression, measured through the activation of eYfp by removal of a "Stop"
      signal (LoxP-Stop-LoxP-eYfp reporter mouse), is present at the onset of terminal
      differentiation and mimics closely the native Pitx3 expression domain. In
      conclusion, we present here a new Cre-driver mouse model to be used in the
      restricted ablation of interesting genes in mdDA neurons in order to improve our
      understanding of the underlying molecular programming.

PMID- 22870340
TI  - Predictors of mortality in patients successfully weaned from extracorporeal
      membrane oxygenation.
AB  - PURPOSE: Extracorporeal membrane oxygenation (ECMO) has been utilized for
      critically ill patients, such as those with life-threatening respiratory failure
      or post-cardiotomy cardiogenic shock. This study compares the predictive value of
      Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II), Sequential
      Organ Failure Assessment (SOFA), and Organ System Failure (OSF) obtained on the
      first day of ECMO removal, and the Acute Kidney Injury Network (AKIN) stages
      obtained at 48 hours post-ECMO removal (AKIN(48-hour)) in terms of hospital
      mortality for critically ill patients. METHODS: This study reviewed the medical
      records of 119 critically ill patients successfully weaned from ECMO at the
      specialized intensive care unit of a tertiary-care university hospital between
      July 2006 and October 2010. Demographic, clinical, and laboratory data were
      collected retrospectively as survival predictors. RESULTS: Overall mortality rate
      was 26%. The most common condition requiring ECMO support was cardiogenic shock.
      By using the areas under the receiver operating characteristic (AUROC) curve, the
      Sequential Organ Failure Assessment (SOFA) score displayed good discriminative
      power (AUROC 0.805+/-0.055, p<0.001). Furthermore, multiple logistic regression
      analysis indicated that daily urine output on the second day of ECMO removal
      (UO(24-48 hour)), mean arterial pressure (MAP), and SOFA score on the day of ECMO
      removal were independent predictors of hospital mortality. Finally, cumulative
      survival rates at 6-month follow-up differed significantly (p<0.001) for a SOFA
      score<=13 relative to those for a SOFA score>13. CONCLUSIONS: Following
      successful ECMO weaning, the SOFA score proved a reproducible evaluation tool
      with good prognostic abilities.

PMID- 22870341
TI  - The proteolytic activity of separase in BCR-ABL-positive cells is increased by
      imatinib.
AB  - Separase, an endopeptidase required for the separation of sister-chromatides in
      mitotic anaphase, triggers centriole disengagement during centrosome duplication.
      In cancer, separase is frequently overexpressed, pointing to a functional role as
      an aneuploidy promoter associated with centrosomal amplification and genomic
      instability. Recently, we have shown that centrosomal amplification and
      subsequent chromosomal aberrations are a hallmark of chronic myeloid leukemia
      (CML), increasing from chronic phase (CP) toward blast crisis (BC). Moreover, a
      functional linkage of p210BCR-ABL tyrosine kinase activity with centrosomal
      amplification and clonal evolution has been established in long-term cell culture
      experiments. Unexpectedly, therapeutic doses of imatinib (IM) did not counteract;
      instead induced similar centrosomal alterations in vitro. We investigated the
      influence of IM and p210BCR-ABL on Separase as a potential driver of centrosomal
      amplification in CML. Short-term cell cultures of p210BCR-ABL-negative (NHDF,
      UROtsa, HL-60, U937), positive (K562, LAMA-84) and inducible (U937p210BCR-ABL/c6
      (Tet-ON)) human cell lines were treated with therapeutic doses of IM and analyzed
      by qRT-PCR, Western blot analysis and quantitative Separase activity assays.
      Decreased Separase protein levels were observed in all cells treated with IM in a
      dose dependent manner. Accordingly, in all p210BCR-ABL-negative cell lines,
      decreased proteolytic activity of Separase was found. In contrast, p210BCR-ABL
      positive cells showed increased Separase proteolytic activity. This activation of
      Separase was consistent with changes in the expression levels of Separase
      regulators (Separase phosphorylation at serine residue 1126, Securin, CyclinB1
      and PP2A). Our data suggest that regulation of Separase in IM-treated BCR-ABL
      positive cells occurs on both the protein expression and the proteolytic activity
      levels. Activation of Separase proteolytic activity exclusively in p210BCR-ABL
      positive cells during IM treatment may act as a driving force for centrosomal
      amplification, contributing to genomic instability, clonal evolution and
      resistance in CML.

PMID- 22870342
TI  - Ethanol seeking by Long Evans rats is not always a goal-directed behavior.
AB  - BACKGROUND: Two parallel and interacting processes are said to underlie animal
      behavior, whereby learning and performance of a behavior is at first via
      conscious and deliberate (goal-directed) processes, but after initial
      acquisition, the behavior can become automatic and stimulus-elicited (habitual).
      With respect to instrumental behaviors, animal learning studies suggest that the
      duration of training and the action-outcome contingency are two factors involved
      in the emergence of habitual seeking of "natural" reinforcers (e.g., sweet
      solutions, food or sucrose pellets). To rigorously test whether behaviors
      reinforced by abused substances such as ethanol, in particular, similarly become
      habitual was the primary aim of this study. METHODOLOGY/PRINCIPAL FINDINGS: Male
      Long Evans rats underwent extended or limited operant lever press training with
      10% sucrose/10% ethanol (10S10E) reinforcement (variable interval (VI) or (VR)
      ratio schedule of reinforcement), or with 10% sucrose (10S) reinforcement (VI
      schedule only). Once training and pretesting were complete, the impact of outcome
      devaluation on operant behavior was evaluated after lithium chloride injections
      were paired with the reinforcer, or unpaired 24 hours later. After limited, but
      not extended instrumental training, lever pressing by groups trained under VR
      with 10S10E and under VI with 10S was sensitive to outcome devaluation. In
      contrast, responding by both the extended and limited training 10S10E VI groups
      was not sensitive to ethanol devaluation during the test for habitual behavior.
      CONCLUSIONS/SIGNIFICANCE: Operant behavior by rats trained to self-administer an
      ethanol-sucrose solution showed variable sensitivity to a change in the value of
      ethanol, with relative insensitivity developing sooner in animals that received
      time-variable ethanol reinforcement during training sessions. One important
      implication, with respect to substance abuse in humans, is that initial learning
      about the relationship between instrumental actions and the opportunity to
      consume ethanol-containing drinks can influence the time course for the
      development or expression of habitual ethanol seeking behavior.

PMID- 22870343
TI  - The skin: A powerful hormone factory.

PMID- 22870344
TI  - Does rosuvastatin increase serum levels of 25-hydroxy-vitamin D?
AB  - An observational study and a "clinical trial" seem to prove that rosuvastatin
      (but not fluvastatin) dramatically increases serum levels of 25-(OH)-D3 (three
      fold above starting values). A critical analysis of the two publications,
      presented below, raises serious concerns. Conclusions from these two studies have
      already been drawn in the scientific literature.It is argued that claiming or
      believing in a "novel pleiotropic effect of rosuvastatin" may be misleading and
      premature.

PMID- 22870345
TI  - Statins and vitamin D: A hot topic that will be discussed for a long time.

PMID- 22870346
TI  - The statin D-lemma.

PMID- 22870347
TI  - On the roles of solar UV irradiance and smoking on the diagnosis of second
      cancers after diagnosis of melanoma.
AB  - Several recent papers have reported standardized incidence ratios (SIRs) for
      second cancers after diagnosis of cutaneous malignant melanoma. This review
      divides the types of cancer into five types: (1) those for which UV-B (UVB)
      irradiance and vitamin D reduces risk; (2) those for which UVB/vitamin D reduces
      risk and smoking increases risk; (3) smoking related; (4) unknown UVB/vitamin D
      and smoking sensitivity and (5) those for which UV irradiance increases risk. For
      those in category 1, SIRs were either significantly elevated or not significantly
      different from 1.0. For those in category 2, the SIR for kidney cancer was
      significantly elevated, whereas the SIRs for cervical, laryngeal and rectal
      cancer were significantly reduced. For those in category 3, all SIRs were
      significantly reduced. For those in categories 4 and 5, SIRs for all types except
      lip cancer were significantly elevated. A registry linkage study found
      significantly reduced SIRs for second cancers after diagnosis of nonmelanoma skin
      cancer in sunny countries but found increased SIRs in less sunny countries. The
      SIRs for second cancer for melanoma were elevated in both sunny and less sunny
      countries. This review concludes that sun exposure without sufficient vitamin D
      production may explain the elevated SIRs for vitamin D-sensitive cancers, whereas
      smoking-through production of skin elastosis, thereby reducing the risk of
      melanoma-probably explains the findings for smoking-related cancers. Thus,
      guidelines on UV irradiance should emphasize regular moderate UVB irradiance
      rather than avoidance for those who can tan.

PMID- 22870348
TI  - How do solar UV irradiance and smoking impact the diagnosis of second cancers
      after diagnosis of melanoma?: No answer yet.
AB  - It may be useful to look at the risk patterns for developing a second primary
      malignancy after a first primary melanoma diagnosis in order to understand the
      etiology and mortality due to melanoma. In this volume, W.B. Grant has proposed
      the interesting hypothesis that solar UV radiation and smoking may be inversely
      associated with the development of melanoma through the presence of dermal or
      solar elastosis. However, this association is inconsistent and may be explained
      by confounding by outdoor activity, physical exercise, obesity, diet and
      underlying immune or genetic factors.

PMID- 22870350
TI  - Advanced glycation end products measured by skin autofluorescence in a population
      with central obesity.
AB  - Accumulation of advanced glycation end products (AGEs) is enhanced by chronic
      hyperglycemia and oxidative stress and this process may contribute to the
      pathogenesis of vascular disease. Skin autofluorescence (AF), a measure of
      accumulation of AGEs in skin collagen, is associated with vascular disease in
      patients with diabetes.    Because central obesity enhances oxidative stress
      people with central obesity might already have increased accumulation of AGEs
      before diabetes or cardiovascular disease become manifest. To test this
      hypothesis, we compared the distribution of skin AF and its association with
      clinical and biochemical parameters in individuals with and without central
      obesity. Skin AF was measured by a validated AGE Reader in 816 persons with and
      431 persons without central obesity, aged 20-70 y. Mean skin AF increased with
      age and smoking and was higher in centrally obese individuals compared with non
      obese individuals (p = 0.001, after adjustment for age and smoking p = 0.13).
      Mean skin AF in the subgroups without central obesity and without other risk
      factors (n = 106), central obesity without other risk factors (n = 74) and
      central obesity with other risk factors (n = 742) was 1.63 +/- 0.37, 1.74 +/-
      0.44 and 1.87 +/- 0.43 AU, respectively (p for trend < 0.001, after adjustment
      for age and smoking p for trend = 0.12). In the group with central obesity age,
      current smoking, alcohol consumption, waist circumference, creatinine clearance
      and hs-CRP were independently associated with skin AF (R(2) = 29.4%). Waist
      circumference hardly contributed to the explained variance. The relationship
      between waist circumference and skin AF is not as obvious as we hypothesized.

PMID- 22870351
TI  - Vitamin D and calcium status in urban children attending an ambulatory clinic
      service in the United Arab Emirates.
AB  - BACKGROUND: Maintaining a normal vitamin D status is important for both skeletal
      and extra-skeletal health. Recent data show that vitamin D deficiency is endemic
      in women residing in the Arabian Gulf and is common in pregnant women and their
      newborns. The purpose of this study was to establish the vitamin D and calcium
      status of children in an urban ambulatory pediatric clinic in Abu Dhabi to
      determine for the prevalence of vitamin D deficiency in this cohort. METHODS:
      Patients were recruited prospectively from the pediatric outpatient clinic
      visits, if they were having blood taken for laboratory investigations other than
      those related to vitamin D and calcium status. The vitamin D status was compared
      between 4 age groups (0-0.9 y, 1-1.9 y, 2-7.9 y and 8 -14 y) using the following
      definitions: deficiency < 25 nmol/l, insufficiency 25-50 nmol/l and sufficiency >
      50 nmol/l. RESULTS: A total of 183 children were included in the study. The
      percentage of females and males in the deficient range was 21% and 16%
      respectively, while 32% and 46% of females and males respectively were vitamin D
      sufficient. The highest prevalence of vitamin D deficiency occurred in the 8-14 y
      old age group with 31.2% being deficient. CONCLUSIONS: The study highlights that
      in an ambulatory pediatric clinic population, peri-pubescent children are most at
      risk of vitamin D deficiency. This age group is often not considered in the
      discussion for the need for vitamin D supplementation. Serious consideration
      should be given to including vitamin D supplementation in a school public health
      program in the UAE.

PMID- 22870349
TI  - Dietary intervention in acne: Attenuation of increased mTORC1 signaling promoted
      by Western diet.
AB  - The purpose of this paper is to highlight the endocrine signaling of Western
      diet, a fundamental environmental factor involved in the pathogenesis of epidemic
      acne. Western nutrition is characterized by high calorie uptake, high glycemic
      load, high fat and meat intake, as well as increased consumption of insulin- and
      IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are
      sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1
      (mTORC1), which integrates signals of cellular energy, growth factors (insulin,
      IGF-1) and protein-derived signals, predominantly leucine, provided in high
      amounts by milk proteins and meat. mTORC1 activates SREBP, the master
      transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling
      and leucine is directly converted by sebocytes into fatty acids and sterols for
      sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone
      secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous
      follicles. Testosterone directly activates mTORC1. Future research should
      investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is
      conceivable that isotretinoin may downregulate mTORC1 in sebocytes by
      upregulation of nuclear levels of FoxO1. The role of Western diet in acne can
      only be fully appreciated when all stimulatory inputs for maximal mTORC1
      activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered.
      Epidemic acne has to be recognized as an mTORC1-driven disease of civilization
      like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new
      insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis
      for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1)
      total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy
      proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary
      changes are opposed to the evolution of industrialized food and fast food
      distribution of Westernized countries. An attenuation of mTORC1 signaling is only
      possible by increasing the consumption of vegetables and fruit, the major
      components of vegan or Paleolithic diets. The dermatologist bears a tremendous
      responsibility for his young acne patients who should be advised to modify their
      dietary habits in order to reduce activating stimuli of mTORC1, not only to
      improve acne but to prevent the harmful and expensive march to other mTORC1
      related chronic diseases later in life.

PMID- 22870352
TI  - No evidence for induction of key components of the Notch signaling pathway (Notch
      1, Jagged-1) by treatment with UV-B, 1,25(OH)(2)D(3), and/or epigenetic drugs
      (TSA, 5-Aza) in human keratinocytes in vitro.
AB  - Notch signaling is of high importance for growth and survival of various cell
      types. We now analyzed the protein expression of two key components of the Notch
      signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and
      in malignant (SCL-1) human keratinocytes, using western analysis. We found that
      Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines,
      with no marked change following UV-B treatment. Moreover, treatment of both cell
      lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D(3), the
      biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5
      Aza) did not result in a marked modulation of the protein expression of Notch-1
      or Jagged-1. Under the experimental conditions of this study, treatment with
      1,25(OH)(2)D(3) protected human keratinocytes in part against the
      antiproliferative effects of UV-B-radiation. In conclusion, our findings do not
      point at a differential expression of these two key components of Notch signaling
      in non-malignant as compared to malignant human keratinocytes, indicating that
      alterations in their expression are not of importance for the photocarcinogenesis
      of human squamous cell carcinomas. Moreover, our findings do not support the
      hypothesis that modulation of Notch signaling may be involved in the
      photoprotective effect of 1,25-dihydroxyvitamin D(3), that we and others reported
      previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5
      Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated
      human keratinocytes in vitro.

PMID- 22870353
TI  - When are laboratory tests indicated in patients with vitiligo?
AB  - BACKGROUND: Vitiligo has been associated with multiple endocrine and immune
      conditions. Several laboratory tests have been assessed in this disease with
      controversial results. OBJECTIVE: The aim of this study is to analyze the levels
      autoantibodies, basal glycaemia, vitamin B12, folic acid and thyroid function and
      its association with the diagnosis and outcome of vitiligo patients through a
      case-control study. MATERIAL AND METHODS: This case-control study was performed
      on 196 consecutive patients with vitiligo referred to our Dermatology Department.
      As a control group, 160 healthy individuals without vitiligo or known history of
      immunologic/endocrine disease were included. Data were analyzed using the SPSS
      17.0 statistical software package. RESULTS: Clinical, analytical and demographic
      data have been recorded. Our results showed that anti-thyroid peroxidase antibody
      and anti-parietal gastric cell antibody could be useful laboratory markers in a
      subpopulation of vitiligo patients. However, testing anti-nuclear antibody, anti
      thyroglobulin antibody, folic acid and vitamin B12 seems to have limited clinical
      implication and diagnostic relevance in our routine clinical practice.
      LIMITATIONS: This study addressed a selected population of vitiligo patients in
      Spain and may not generalize to different clinical settings or regions. The study
      of a wider sample would confirm these findings and allow a detailed analysis of
      the above factors as a function of the clinical subtype of vitiligo. CONCLUSION:
      We have determined the more efficient serological markers to order in vitiligo
      patients. Our findings suggest that anti-thyroid peroxidase antibody and anti
      parietal gastric cell could be useful tests for the characterization of specific
      subpopulations of vitiligo patients in terms of severity and co-morbidity, so
      their determination could have a prognostic value.

PMID- 22870354
TI  - Age and skin site related differences in steroid metabolism in male skin point to
      a key role of sebocytes in cutaneous hormone metabolism.
AB  - Hormone concentrations decline with aging. Up to now it was not clear, whether
      the decrease of hormone concentrations in blood samples are also present in
      cutaneous suction blister fluids, and whether skin from different anatomical
      sites shows different hormone concentrations.Analysis of suction blister fluids
      and paired blood samples from young (mean 27.8 y) and old (mean 62.6 y) male
      subjects by UPLC-MS/MS showed that DHEA concentration in blood samples was age
      dependently significantly reduced, but increased in suction blister fluids, while
      androstenedione behaved in an opposite manner to DHEA. Testosterone decreased age
      dependently in blood samples and in suction blister fluids. Regarding skin sites,
      DHEA was lower in samples from upper back compared with samples from the forearm.
      In contrast, the concentrations of androstenedione and testosterone were higher
      in samples from upper back.In vitro analyses showed that SZ95 sebocytes, but
      neither primary fibroblasts nor keratinocytes, were able to use DHEA as precursor
      for testosterone biosynthesis, which was confirmed by expression analysis of
      3beta-hydroxysteroiddehydrogenase in skin biopsies.In conclusion, we show an
      inverse pattern of DHEA and androstenedione concentrations in blood vs. suction
      blister fluids, highlighting age-dependent changes of dermal testosterone
      biosynthesis, and a stronger metabolism in young skin. Furthermore, sebocytes
      play a central role in cutaneous androgen metabolism.

PMID- 22870355
TI  - Hair loss and hyperprolactinemia in women.
AB  - In the literature of the past 30 years there are only some publications concerned
      with hair loss and hyperprolactinemia in women. Therefore, the relevance of
      hyperprolactinemia was evaluated in 40 women with diffuse alopecia.Hair loss was
      assessed by clinical appearance and the pluck trichogram. 82.5% of the female
      patients had diffuse hair loss and 17.5% had androgenetic alopecia.The highest
      prolactin values measured were 1390 ng/ml and 255 ng/ml. Six patients had values
      between 150-80.4 ng/ml and 10 between 79.1-51.7 ng/ml. All others had prolactin
      values below 50 ng/ml. Fifteen untreated patients with elevated prolactin levels
      could be followed up. Without any prolactin-inhibiting drugs, reductions and
      normalizations beside moderate fluctuations could be detected.Thyroid-specific
      diagnostics showed in 95% of the patients a normal thyroid function. 2.5% had a
      slight hyperthyreoidism and 2.5% had a slight hypothyreoidism. No female patient
      had clinical signs of androgenization and the determined androgens testosterone,
      androstendione and dihydroepiandrostendione were in the normal range.According to
      these results, moderate elevated prolactin levels in association with diffuse or
      androgenetic hair loss can be neglected as causative for the hair loss, because
      there is no evidence that they have an influence to the pattern, the extent or
      the duration of the hair loss. These results are supported by investigations of
      other authors who described only in high doses of prolactin an inhibiting effect
      on human hair follicles in vitro. Nevertheless, moderate constantly elevated
      prolactin levels should induce further diagnostics to exclude a prolactin
      producing tumor of the pituitary gland.

PMID- 22870356
TI  - Vitamin D-insufficiency: An estimate of the situation in Germany.
AB  - BACKGROUND: Vitamin D insufficiency is increasingly recognized as an important
      risk factor in the pathogenesis of falls and fractures and may increase the risk
      of other diseases. The aim of this study was to obtain information about the
      vitamin D supply from a representative cohort of the German population.   
      METHODS: 264 General practitioners participated in the DeViD-Trial (D-Vitamin in
      Deutschland) by taking blood samples from their consenting daily ambulant
      patients regardless of the actual reason for consultation. In these blood samples
      vitamin D [25(OH)D] and other related parameters were measured at a central
      laboratory. The patients filled in a simple questionnaire (i.e., age, sex, etc.).
      The trial was performed between February 26 and May 25, 2007. RESULTS: Laboratory
      and personal data were documented for 1,343 individuals (615 men, 728 women). The
      age distribution ranged from 20 to 99 y, the mean age of the whole cohort was
      57.6 y (men 58.2, women 57.2). The mean 25-OH-D-value for the whole cohort was
      16.2 ng/ml (range: 6.0 to 66.8, median 14.1 ng/ml). Ten percent of the patients
      had 25(OH)D-values below 7 ng/ml, 65% below 20 ng/ml and 92% showed values below
      30 ng/ml. In the more recent literature, 25(OH)D values below 30 ng/ml are
      regarded as sub-optimal for bone, muscle and general health. Correspondingly it
      can be stated that in this representative population there is a high prevalence
      of moderate to severe vitamin D-insufficiency regardless of young or old age.

PMID- 22870357
TI  - The use of ketamine for perioperative pain management.

PMID- 22870358
TI  - Concerns of the anesthesiologist: anesthetic induction in severe sepsis or septic
      shock patients.
AB  - Septic patients portray instable hemodynamic states because of hypotension or
      cardiomyopathy, caused by vasodilation, thus, impairing global tissue perfusion
      and oxygenation threatening functions of critical organs. Therefore, it has
      become the primary concern of anesthesiologists in conducting anesthesia
      (induction, maintenance, recovery, and postoperative care), especially in the
      induction of those who are prone to fall into hemodynamic crisis, due to
      hemodynamic instability. The anesthesiologist must have a precise anesthetic plan
      based on a thorough preanesthetic evaluation because many cases are emergent.
      Primary circulatory status of patients, including mental status, blood pressure,
      urine output, and skin perfusion, are necessary, as well as more active
      assessment methods on intravascular volume status and cardiovascular function.
      Because it is difficult to accurately evaluate the intravascular volume, only by
      central venous pressure (CVP) measurements, the additional use of transthoracic
      echocardiography is recommended for the evaluation of myocardial performance and
      hemodynamic state. In order to hemodynamically stabilize septic patients,
      adequate fluid resuscitation must be given before induction. Most anesthetic
      induction agents cause blood pressure decline, however, it may be useful to use
      drugs, such as ketamine or etomidate, which carry less cardiovascular instability
      effects than propofol, thiopental and midazolam. However, if blood pressure is
      unstable, despite these efforts, vasopressors and inotropic agents must be
      administered to maintain adequate perfusion of organs and cellular oxygen uptake.

PMID- 22870359
TI  - Comparison of the renal safety between carbon dioxide absorbent products under
      sevoflurane anesthesia: a pilot study.
AB  - BACKGROUND: The chemical reaction of carbon dioxide absorbent and sevoflurane is
      known to produce compound A. However, carbon dioxide absorbents are not
      controlled by the Food and Drug Administration, but are treated as industrial
      products in some nations. Moreover, carbon dioxide absorbents differ in their
      capacities to produce compound A, because their chemical compositions differ. In
      this study, we compared the renal safety between carbon dioxide absorbent
      products in patients under sevoflurane anesthesia. METHODS: Eighty patients with
      no preexisting renal disease undergoing elective gynecologic surgery were
      randomly assigned to receive sevoflurane or isoflurane anesthesia with one of
      four carbon dioxide absorbent products (Sodasorblime(r), Sodalyme(r),
      Sodasorb(r), Spherasorb(r)) at the same fresh gas flow of 2 L/min. The renal
      safety was evaluated by changes of blood urea nitrogen (BUN), creatinine and
      urine N-acetyl-b-glucoseaminidase (NAG)-creatinine ratio at 24 hours and 72 hours
      after surgery from preoperative level. RESULTS: There was no significant
      difference in the renal safety indicators between carbon dioxide absorbents
      during sevoflurane anesthesia (P > 0.05). However, the BUN and urine NAG
      creatinine ratios at 72 hours after surgery were higher in isoflurane anesthesia
      in some carbon dioxide absorbent groups (P = 0.03 and 0.04, respectively).
      CONCLUSIONS: We could not find significant differences of renal safety indicators
      with carbon dioxide absorbents. Although the adverse effect of carbon dioxide
      absorbents on renal function was not proved, consideration should be given to
      their contol by the regulation on their efficacy and safety because carbon
      dioxide absorbents can produce compound A.

PMID- 22870360
TI  - In vivo effects of different anesthetic agents on apoptosis.
AB  - BACKGROUND: This study was designed to measure in vivo effects of propofol,
      isoflurane and sevoflurane on apoptosis by measuring caspase-3 and tumor necrosis
      factor (TNF)-related apoptosis inducing ligand (TRAIL) blood level as apoptotic
      markers. METHODS: After obtaining ethical committee approval and informed written
      consents, sixty adult patients ASA I scheduled for open cholecystectomy
      participated in this study. They were randomally allocated into one of three
      equal groups to receive propofol infusion, low-flow isoflurane or sevoflurane for
      maintenance of anesthesia. Venous blood samples were collected preoperatively,
      immediately postoperative and after 24 hours to measure hemoglobin, hematocrit,
      creatinine, liver enzymes, serum TRAIL and caspase-3 levels. RESULTS: There was
      no significant difference in hematological markers and serum creatinine. Liver
      enzymes showed significant postoperative rise (P < 0.05). In Propofol group,
      TRAIL and caspase-3 levels were significantly elevated immediately postoperative
      then decreased significantly after 24-hours (P < 0.05). In Isoflurane group,
      immediate postoperative level of TRAIL was significantly higher than 24 hours
      reading and significantly lower than its level in Propofol group at the same
      timing meanwhile caspase-3 levels were comparable at different timings. In
      Sevoflurane group, TRAIL and caspase-3 levels increased significantly in both
      postoperative samples than preoperative level and than those of Isoflurane and
      Propofol groups after 24 hours concerning TRAIL (P & 0.05). CONCLUSIONS: This
      study concluded that isoflurane is superior and sevoflurane is the least
      effective among the three anesthetics in protection against apoptosis. This study
      neither proved nor excluded propofol-induced apoptosis. Further studies are
      required during lengthy procedure and in compromised patients.

PMID- 22870361
TI  - Effect of a target-controlled infusion of remifentanil in combination with
      desflurane during the "maintenance" phase of general anesthesia.
AB  - BACKGROUND: The goal of this study was to determine the optimal target-controlled
      concentration of remifentanil combined with desflurane, by using a more widely
      and decreasing end-tidal concentration of desflurane. METHODS: Ninety ASA I
      patients, who underwent general anesthesia for elective orthopedic or extremity
      surgeries, were registered and randomly allocated to receive either a target
      controlled concentration of 1 ng/ml (group R1), 2 ng/ml (group R2) remifentanil,
      or desflurane only without remifentanil infusion (group D). Mean arterial
      pressure (MAP) and heart rate (HR) were recorded at 5-min intervals from after a
      10-15 min period of surgical incision to before a 10-min period prior to the end
      of an operation. End-tidal concentration of desflurane was increased or decreased
      in proportion to the changes in MAP and HR. If the value of bispectral index
      (BIS) was from 60-62 for more than 2 min or systolic blood pressure would fall
      below 90 mmHg, the patient was excluded from the study to prevent a risk of
      "explicit awareness" and shock. RESULTS: The end-tidal desflurane concentration
      was lower in the group receiving 1 ng/ml (5.2 +/- 0.5 vol%; P < 0.001) and 2
      ng/ml remifenanil (4.4 +/- 0.5 vol%; P < 0.001) compared to patients in group D
      (7.9 +/- 0.5 vol%). CONCLUSIONS: We recommend the use of 2 ng/ml or less
      remifentanil combined with desflurane for decreasing concentrations of desflurane
      without significant side effects, during the "maintenance" phase, and not during
      the induction phase of general anesthesia.

PMID- 22870362
TI  - A target-controlled infusion regimen for reducing remifentanil-induced coughs.
AB  - BACKGROUND: This study evaluates the effectiveness of the target-controlled
      infusion (TCI) of remifentanil through stepwise increases in the effect-site
      concentration (C(eff)) in preventing coughs. METHODS: In a preliminary study, we
      randomly selected 140 patients to receive remifentanil through two-step increases
      in C(eff) (1.0 ng/ml to 4.0 ng/ml: Group R(1-4); 2.0 ng/ml to 4.0 ng/ml: Group
      R(2-4)). Based on the results of the preliminary study, we employed another
      sample of 140 patients and implemented a three-step increase in TCI (1.0 ng/ml to
      2.0 ng/ml to 4.0 ng/ml: Group R(1-2-4)). We then compared this treatment with
      direct targeting based on 4.0 ng/ml TCI (Group R(4)). We recorded the episodes of
      coughs, rating them as mild (1-2), moderate (3-4), or severe (5 or more).
      RESULTS: In Group R(1-4), one patient (1.5%) coughed during the first step, and
      five (7.3%) coughed during the second step. In Group R(2-4), nine (13.2%) coughed
      during the first step, but none coughed during the next step. Only one patient
      had a mild cough during the three-step increase in TCI, that is, patients in
      Group R(1-2-4) were significantly less likely to cough than those in Group R(4)
      (P < 0.001). CONCLUSIONS: Stepwise increases in the TCI of remifentanil reduced
      the incidence of remifentanil-induced coughing, and the three-step increase in
      TCI nearly eliminated remifentanil-induced coughing.

PMID- 22870363
TI  - Effects of increasing the dose of ropivacaine on vertical infraclavicular block
      using neurostimulation.
AB  - BACKGROUND: Use of an infraclavicular block is appropriate for surgery of the
      upper limb. However, it does not consistently block the entire brachial plexus.
      The aim of this study was to investigate whether increasing the dose of
      ropivacaine could enhance the success rate, onset time, and efficacy of the
      sensory and motor block during the use of a vertical infraclavicular block using
      neurostimulation in upper limb surgery. METHODS: TWO HUNDREDS AND TEN PATIENTS
      WERE PROSPECTIVELY RANDOMIZED INTO THREE GROUPS: Group 1 (30 ml of 0.5%
      ropivacaine; n = 70), Group 2 (40 ml of 0.5% ropivacaine; n = 70), and Group 3
      (40 ml of 0.75% ropivacaine; n = 70). Patients in each group received a vertical
      infraclavicular block using neurostimulation and obtained a distal motor response
      of the ulnar or median nerve. Recorded outcome measures included block success
      rate, onset time, sensory and motor blocks, and adverse events. RESULTS: No
      differences were found in the block success rate among the three groups (92.8%,
      97.1%, and 94.2% for Groups 1, 2, and, 3, respectively; P = 0.346). There were no
      significant differences in onset time (P = 0.225) among groups, nor was there
      enhancement in the sensory block, but the motor block was enhanced. Local
      anesthetic toxicity was observed in five female patients from group 3 (P =
      0.006). CONCLUSIONS: Although the efficacy of the motor block was significantly
      improved, success rate, onset time, and efficacy of sensory block were not
      enhanced significantly among groups despite differences in volume and
      volume/concentration of the local anesthetic.

PMID- 22870364
TI  - Anesthetic review of emergency peripartum hysterectomy following vaginal and
      cesarean delivery: a retrospective study.
AB  - BACKGROUND: The purpose of this study was to review incidence, indications,
      complications, and the anesthetic management of emergency obstetric
      hysterectomies. METHODS: This was a retrospective study of the cases of emergency
      obstetric hysterectomies performed at the Woman's Hospital over a 3 year period
      between January 2008 and December 2010. The indication for surgery, anesthetic
      management, operating time, estimated blood loss, pre- and postoperative
      hemoglobin and hematocrit values, need for blood transfusion, and perioperative
      complications were obtained. RESULTS: During the study period there were 46
      emergency obstetric hysterectomies for 20147 deliveries, giving an incidence of
      2.28/1000 deliveries. The number of emergency hysterectomies was significantly
      higher with the cesarean deliveries than with the vaginal deliveries. The most
      common indication for emergency obstetric hysterectomy was placenta accreta.
      Postoperatively, Dissemimated Intravascular Coagulation (DIC) was the most common
      complication. CONCLUSIONS: Abnormal placenta has been an main indication of
      emergency hysterectomy. Anesthesiologists should be eligible to aware of high
      risk of emergency hysterectomy and deal with massive hemorrhage.

PMID- 22870365
TI  - A comparative study of emergence agitation between sevoflurane and propofol
      anesthesia in adults after closed reduction of nasal bone fracture.
AB  - BACKGROUND: Emergence agitation is associated with increased morbidity and
      hospital costs. However, there have been few reports in the medical literature on
      the occurrence of emergence agitation in adults. The aim of this study was to
      compare emergence agitation between sevoflurane and propofol anesthesia in adults
      after closed reduction of nasal bone fracture. METHODS: Forty adults (ASA I-II,
      20-60 yr) undergoing closed reduction of nasal bone fracture were randomly
      assigned to either sevoflurane or propofol group and anesthesia was maintained
      with sevoflurane or propofol. The bispectral index (BIS) was monitored and
      maintained within 40-60. At the end of surgery, patients were transported to the
      post anesthetic care unit (PACU) and agitation state scale was checked by Aono's
      four-point scale (AFPS). Emergence agitation was defined as and AFPS score of 3
      or 4. Pain score were measured by numeric rating scale (NRS) on arrival and peak
      value at PACU. RESULTS: Nine (45.0%) patients in the sevoflurane group and 2
      (10.0%) patients in the propofol group developed emergence agitation in the PACU
      (P = 0.031). There was no correlation between peak NRS and Aono's four-point
      scale. CONCLUSIONS: Propofol may decrease incidence of emergence agitation
      compared to sevoflurane in adults undergoing closed reduction of nasal bone
      fracture.

PMID- 22870366
TI  - Peri-operative ketamine with the ambulatory elastometric infusion pump as an
      adjuvant to manage acute postoperative pain after spinal fusion in adults: a
      prospective randomized trial.
AB  - BACKGROUND: In this study, we assessed the effectiveness of ketamine as an
      alternative to non-steroidal anti-inflammatory drugs (NSAID), to manage acute
      postoperative pain after spinal fusion when given intravenously via a patient
      controlled analgesia (PCA) pump in which the dose was proportional to that of
      fentanyl. METHODS: Forty patients undergoing 1-2 level spinal fusion were
      enrolled in this study. Patients were intraoperatively randomized into two groups
      to receive intravenous PCA consisting either of fentanyl 0.4 ug/ml/kg (control
      group) or fentanyl 0.4 ug/ml/kg with ketamine 30 ug/ml/kg (ketamine group) after
      intravenous injection of a loading dose. The loading dose in the control group
      was fentanyl 1 ug/kg with normal saline equal to ketamine volume and in the
      ketamine group it was fentanyl 1 ug/kg with ketamine 0.2 mg/kg. The verbal
      numerical rating scale (NRS), fentanyl and ketamine infusion rate, and side
      effects were evaluated at 1, 24, and 48 hours after surgery. RESULTS: There were
      no significant differences in patient demographics, duration of surgery and
      anesthesia or intra-operative opioids administration. We did not find any
      significant differences in the mean infusion rate of intraoperative remifentanil
      or postoperative fentanyl or in the side effects between the groups, but we did
      find a significant difference in the NRS between the groups. CONCLUSIONS: Based
      on our results, we conclude that a small dose of ketamine (0.5-2.5 ug/kg/min)
      proportional to fentanyl is not only safe, but also lowers postoperative pain
      intensity in patients undergoing spinal fusion, although the opioid-sparing
      effects of ketamine were not demonstrated.

PMID- 22870367
TI  - Ultrasound visibility of regional anesthesia catheters: an in vitro study.
AB  - BACKGROUND: Ultrasound subjective visibility of in-plane needles is correlated
      with the intensity difference between the needle surface and the background.
      Regional anesthesia catheters are difficult to visualize by an ultrasound. In the
      present study, we investigated the ultrasound visibility of the catheters.
      METHODS: Six catheters were placed at 0 degrees  and 30 degrees  relative to and
      at a depth of 1 cm below the pork phantom surface. Ultrasound images of in-plane
      catheters were evaluated, subjectively and objectively. Outer and inner objective
      visibilities were defined as the difference in the mean pixel intensity between
      the catheter surface and adjacent background, and between the surface and the
      center of the catheter, respectively. Evaluations were made based on the portion
      of the catheters. A P value < 0.05 was considered significant. RESULTS:
      Subjective visibility was more strongly correlated with the inner objective
      visibility than with the outer objective visibility at both angles. Metallic 19
      gauge catheters were more subjectively visible than the non-metallic 20-gauge
      catheters at 30 degrees  degrees (P < 0.01). Subjective, and outer and inner
      objective visibility were significantly lower at 30 degrees  than at 0 degrees 
      (P < 0.01, P < 0.01, P = 0.02). Perifix ONE at 0 degrees  and Perifix FX at 30
      degrees  were the most visible catheters (P < 0.01 for both). CONCLUSIONS:
      Subjective visibility of catheters can not be evaluated in the same manner as
      that of the needles. For the best possible visualization, we recommend selecting
      a catheter with a structure that enhances the dark at the center of catheter,
      rather than basing the catheter selection on the bore size.

PMID- 22870368
TI  - Airway obstruction after biopsy by cervical mediastinoscopy in a patient with a
      mediastinal mass -A case report-.
AB  - Biopsy, using mediastinoscopy is commonly employed for accurate histologic
      diagnosis of a mediastinal mass. However, since the mass is not removed during
      the procedure, it may cause compression of vital structures such as major
      airways, the heart, the pulmonary artery, and the superior vena cava after
      surgery. We observed a case of a 66-year-old man with a mediastinal mass that
      caused severe airway obstruction during recovery from anesthesia following
      mediastinoscopic biopsy, probably caused by upper airway edema which seemed to
      originate from compression of the superior vena cava. Therefore, we suggest that
      unexpected airway obstruction in a patient with a mediastinal mass can be due to
      superior vena cava compression.

PMID- 22870369
TI  - Severe brachial plexus injury after retropubic radical prostatectomy -A case
      report-.
AB  - A 69-year-old man with prostate cancer underwent surgery for 16 h. Approximately
      6 h after surgery, the patient developed severe pain and motor weakness in his
      right arm. After neurologic examinations that included a nerve conduction study
      and electromyography, the patient was diagnosed with a brachial plexus injury.
      The causes of the brachial plexus injury were thought to be abduction of both
      arms, direct compression of the shoulder brace, and prolonged surgery. Most of
      the postoperative peripheral nerve injuries due to patient position are
      preventable, and anesthetists and surgeons should be very careful in positioning
      the patient accurately.

PMID- 22870370
TI  - Air embolism during off-pump coronary artery bypass graft surgery -A case report
      .
AB  - There have been several reports of gas embolism occurring during off-pump
      coronary artery bypass graft (OPCAB) surgery. However, all these cases of air
      embolism were associated with the repair of venous circulation, using a CO(2)
      blower. In this report, we describe a rare case of air embolism in the coronary
      arteries associated with the use of a CO(2) blower during OPCAB. There was no
      injury to the veins during OPCAB. The air embolism was treated successfully with
      cardiopulmonary bypass.

PMID- 22870371
TI  - Use of perioperative ureteral stent in abdominal aortic aneurysm with
      retroperitoneal fibrosis - A report of two cases -.
AB  - Retroperitoneal fibrosis is associated with fibroblast proliferation due to
      inflammatory changes in adipose/fibrous tissue. Given that aortic dilation in
      abdominal aortic aneurysm can cause compression of the ureter, abdominal aortic
      aneurysm complicated by retroperitoneal fibrosis is likely to result in urinary
      tract obstruction. Accordingly, close attention to changes in perioperative urine
      volume is warranted when operating on patients with abdominal aortic aneurysm
      complicated by retroperitoneal fibrosis. We have recently performed laparotomies
      on two cases of abdominal aortic aneurysm complicated by retroperitoneal
      fibrosis. In the first case, surgery was performed without the placement of a
      ureteral stent. The patient developed postrenal acute renal failure caused by
      postoperative urinary retention. In the second case, ureteral stent placement in
      advance enabled perioperative management without complications. The clinical
      course of these cases suggests that, in laparotomy with concomitant
      retroperitoneal fibrosis, preoperative ureteral stent placement can prevent
      postoperative complications in the renal and urinary systems.

PMID- 22870372
TI  - Cardiac arrest during excision of a huge sacrococcygeal teratoma - A report of
      two cases -.
AB  - Resection of large sacrococcygeal teratomas (SCTs) in premature neonates has been
      associated with significant perinatal mortality, making this a high risk
      procedure requiring careful anesthetic management. Most deaths during resection
      of SCTs are due to cardiac arrest caused by electrolyte imbalances, such as
      hyperkalemia, and massive bleeding during surgery. We describe two premature
      neonates who experienced cardiac arrest, one due to hyperkalemia and the other
      not due to hyperkalemia, during excision of large, prenatally diagnosed SCTs. We
      present here the considerations for anesthesia in premature neonates with huge
      SCTs.

PMID- 22870373
TI  - General anesthetic management of Prader-Willi syndrome patient undergoing middle
      cerebral artery-superficial temporal artery anastomosis.

PMID- 22870374
TI  - Airway management using O(2) flush via Cook airway exchange catheter(r) for
      microlaryngeal surgery.

PMID- 22870375
TI  - An anesthetic management of a patient with Klippel-Trenaunay syndrome.

PMID- 22870376
TI  - Remifentanil or dexmedetomidine for monitored anesthesia care during cataract
      surgery under topical anesthesia.

PMID- 22870377
TI  - DebtRank: too central to fail? Financial networks, the FED and systemic risk.
AB  - Systemic risk, here meant as the risk of default of a large portion of the
      financial system, depends on the network of financial exposures among
      institutions. However, there is no widely accepted methodology to determine the
      systemically important nodes in a network. To fill this gap, we introduce,
      DebtRank, a novel measure of systemic impact inspired by feedback-centrality. As
      an application, we analyse a new and unique dataset on the USD 1.2 trillion FED
      emergency loans program to global financial institutions during 2008-2010. We
      find that a group of 22 institutions, which received most of the funds, form a
      strongly connected graph where each of the nodes becomes systemically important
      at the peak of the crisis. Moreover, a systemic default could have been triggered
      even by small dispersed shocks. The results suggest that the debate on too-big-to
      fail institutions should include the even more serious issue of too-central-to
      fail.

PMID- 22870378
TI  - How to construct the perfect sandcastle.
AB  - Just a bit of water enables one to turn a pile of dry sand into a spectacular
      sandcastle. Too much water however will destabilize the material, as is seen in
      landslides. Here we investigated the stability of wet sand columns to account for
      the maximum height of sandcastles. We find that the columns become unstable to
      elastic buckling under their own weight. This allows to account for the maximum
      height of the sand column; it is found to increase as the 2/3 power of the base
      radius of the column. Measuring the elastic modulus of the wet sand, we find that
      the optimum strength is achieved at a very low liquid volume fraction of about
      1%. Knowing the modulus we can quantitatively account for the measured sandcastle
      heights.

PMID- 22870379
TI  - A new mechanism of stem cell differentiation through slow binding/unbinding of
      regulators to genes.
AB  - Understanding differentiation, a biological process from a multipotent stem or
      progenitor state to a mature cell is critically important. We developed a
      theoretical framework to quantify the underlying potential landscape and pathways
      for cell development and differentiation. We proposed a new mechanism of
      differentiation and found the differentiated states can emerge from the slow
      binding/unbinding of regulatory proteins to gene promoters. With slow promoter
      binding/unbinding, we found multiple meta-stable differentiated states, which can
      explain the origin of multiple states observed in recent experiments. The kinetic
      time for the differentiation and reprogramming strongly depends on the time scale
      of the promoter binding/unbinding processes. We discovered an optimal speed for
      differentiation for certain promoter binding/unbinding rates. Future experiments
      might be able to tell if cells differentiate at that optimal speed. We also
      quantified irreversible kinetic pathways for the differentiation and
      reprogramming, which captures the non-equilibrium dynamics in multipotent stem or
      progenitor cells.

PMID- 22870380
TI  - The evolution of interdisciplinarity in physics research.
AB  - Science, being a social enterprise, is subject to fragmentation into groups that
      focus on specialized areas or topics. Often new advances occur through cross
      fertilization of ideas between sub-fields that otherwise have little overlap as
      they study dissimilar phenomena using different techniques. Thus to explore the
      nature and dynamics of scientific progress one needs to consider the organization
      and interactions between different subject areas. Here, we study the
      relationships between the sub-fields of Physics using the Physics and Astronomy
      Classification Scheme (PACS) codes employed for self-categorization of articles
      published over the past 25 years (1985-2009). We observe a clear trend towards
      increasing interactions between the different sub-fields. The network of sub
      fields also exhibits core-periphery organization, the nucleus being dominated by
      Condensed Matter and General Physics. However, over time Interdisciplinary
      Physics is steadily increasing its share in the network core, reflecting a shift
      in the overall trend of Physics research.

PMID- 22870381
TI  - Localized outbreak of attached diatoms on the coral Montipora due to low
      temperature stress.
AB  - A short-term, localized outbreak of diatoms attached to live corals was observed
      along the coast of Sesoko Island, Okinawa, Japan in February, 2011. Diatoms are
      recognized as brown patches in the initial stage, becoming fluffy encrustations
      and resulting in complete or partial coral death. Attached diatoms, including
      Licmophora, Climacosphenia, Ardissonea and others, attached and overgrew
      exclusively Montipora corals, which are dominant corals in some parts of Sesoko
      reef. Heavily-covered colonies or branches died. The rate of affected corals
      reached 80% in the worst-affected area. Microscopic observation showed that most
      diatoms settled directly with polysaccharide stalks or pads onto the partly-bared
      skeleton of coral branches, although some settled on coral soft tissues. Although
      no similar phenomenon was reported from other areas of Japan, cold-water events
      might have important roles in coral weakening, as a consequence, enabling diatom
      attachment on corals, thus leading to coral death in this area.

PMID- 22870382
TI  - Direct interaction between the Gulf Stream and the shelfbreak south of New
      England.
AB  - Sea surface temperature imagery, satellite altimetry, and a surface drifter track
      reveal an unusual tilt in the Gulf Stream path that brought the Gulf Stream to
      39.9 degrees N near the Middle Atlantic Bight shelfbreak--200 km north of its
      mean position--in October 2011, while a large meander brought Gulf Stream water
      within 12 km of the shelfbreak in December 2011. Near-bottom temperature
      measurements from lobster traps on the outer continental shelf south of New
      England show distinct warming events (temperature increases exceeding 6 degrees
      C) in November and December 2011. Moored profiler measurements over the
      continental slope show high salinities and temperatures, suggesting that the warm
      water on the continental shelf originated in the Gulf Stream. The combination of
      unusual water properties over the shelf and slope in late fall and the subsequent
      mild winter may affect seasonal stratification and habitat selection for marine
      life over the continental shelf in 2012.

PMID- 22870383
TI  - Calcium signaling is gated by a mechanical threshold in three-dimensional
      environments.
AB  - Cells interpret their mechanical environment using diverse signaling pathways
      that affect complex phenotypes. These pathways often interact with ubiquitous
      2(nd)-messengers such as calcium. Understanding mechanically-induced calcium
      signaling is especially important in fibroblasts, cells that exist in three
      dimensional fibrous matrices, sense their mechanical environment, and remodel
      tissue morphology. Here, we examined calcium signaling in fibroblasts using a
      minimal-profile, three-dimensional (MP3D) mechanical assay system, and compared
      responses to those elicited by conventional, two-dimensional magnetic tensile
      cytometry and substratum stretching. Using the MP3D system, we observed robust
      mechanically-induced calcium responses that could not be recreated using either
      two-dimensional technique. Furthermore, we used the MP3D system to identify a
      critical displacement threshold governing an all-or-nothing mechanically-induced
      calcium response. We believe these findings significantly increase our
      understanding of the critical role of calcium signaling in cells in three
      dimensional environments with broad implications in development and disease.

PMID- 22870384
TI  - Actin cap associated focal adhesions and their distinct role in cellular
      mechanosensing.
AB  - The ability for cells to sense and adapt to different physical microenvironments
      plays a critical role in development, immune responses, and cancer metastasis.
      Here we identify a small subset of focal adhesions that terminate fibers in the
      actin cap, a highly ordered filamentous actin structure that is anchored to the
      top of the nucleus by the LINC complexes; these differ from conventional focal
      adhesions in morphology, subcellular organization, movements, turnover dynamics,
      and response to biochemical stimuli. Actin cap associated focal adhesions
      (ACAFAs) dominate cell mechanosensing over a wide range of matrix stiffness, an
      ACAFA-specific function regulated by actomyosin contractility in the actin cap,
      while conventional focal adhesions are restrictively involved in mechanosensing
      for extremely soft substrates. These results establish the perinuclear actin cap
      and associated ACAFAs as major mediators of cellular mechanosensing and a
      critical element of the physical pathway that transduce mechanical cues all the
      way to the nucleus.

PMID- 22870385
TI  - Precise and continuous time and frequency synchronisation at the 5*10-19 accuracy
      level.
AB  - The synchronisation of time and frequency between remote locations is crucial for
      many important applications. Conventional time and frequency dissemination often
      makes use of satellite links. Recently, the communication fibre network has
      become an attractive option for long-distance time and frequency dissemination.
      Here, we demonstrate accurate frequency transfer and time synchronisation via an
      80 km fibre link between Tsinghua University (THU) and the National Institute of
      Metrology of China (NIM). Using a 9.1 GHz microwave modulation and a timing
      signal carried by two continuous-wave lasers and transferred across the same 80
      km urban fibre link, frequency transfer stability at the level of 5*10-19/day was
      achieved. Time synchronisation at the 50 ps precision level was also
      demonstrated. The system is reliable and has operated continuously for several
      months. We further discuss the feasibility of using such frequency and time
      transfer over 1000 km and its applications to long-baseline radio astronomy.

PMID- 22870386
TI  - SNP in starch biosynthesis genes associated with nutritional and functional
      properties of rice.
AB  - Starch is a major component of human diets. The relative contribution of
      variation in the genes of starch biosynthesis to the nutritional and functional
      properties of the rice was evaluated in a rice breeding population. Sequencing 18
      genes involved in starch synthesis in a population of 233 rice breeding lines
      discovered 66 functional SNPs in exonic regions. Five genes, AGPS2b, Isoamylase1,
      SPHOL, SSIIb and SSIVb showed no polymorphism. Association analysis found 31 of
      the SNP were associated with differences in pasting and cooking quality
      properties of the rice lines. Two genes appear to be the major loci controlling
      traits under human selection in rice, GBSSI (waxy gene) and SSIIa. GBSSI
      influenced amylose content and retrogradation. Other genes contributing to
      retrogradation were GPT1, SSI, BEI and SSIIIa. SSIIa explained much of the
      variation in cooking characteristics. Other genes had relatively small effects.

PMID- 22870387
TI  - Radial Photonic Crystal for detection of frequency and position of radiation
      sources.
AB  - Based on the concepts of artificially microstructured materials, i.e.
      metamaterials, we present here the first practical realization of a radial wave
      crystal. This type of device was introduced as a theoretical proposal in the
      field of acoustics, and can be briefly defined as a structured medium with radial
      symmetry, where the constitutive parameters are invariant under radial
      geometrical translations. Our practical demonstration is realized in the
      electromagnetic microwave spectrum, because of the equivalence between the wave
      problems in both fields. A device has been designed, fabricated and
      experimentally characterized. It is able to perform beam shaping of punctual wave
      sources, and also to sense position and frequency of external radiators. Owing to
      the flexibility offered by the design concept, other possible applications are
      discussed.

PMID- 22870388
TI  - Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition
      occurs during G2 in fission yeast.
AB  - The inheritance of the histone H3 variant CENP-A in nucleosomes at centromeres
      following DNA replication is mediated by an epigenetic mechanism. To understand
      the process of epigenetic inheritance, or propagation of histones and histone
      variants, as nucleosomes are disassembled and reassembled in living eukaryotic
      cells, we have explored the feasibility of exploiting photo-activated
      localization microscopy (PALM). PALM of single molecules in living cells has the
      potential to reveal new concepts in cell biology, providing insights into
      stochastic variation in cellular states. However, thus far, its use has been
      limited to studies in bacteria or to processes occurring near the surface of
      eukaryotic cells. With PALM, one literally observes and 'counts' individual
      molecules in cells one-by-one and this allows the recording of images with a
      resolution higher than that determined by the diffraction of light (the so-called
      super-resolution microscopy). Here, we investigate the use of different
      fluorophores and develop procedures to count the centromere-specific histone H3
      variant CENP-A(Cnp1) with single-molecule sensitivity in fission yeast
      (Schizosaccharomyces pombe). The results obtained are validated by and compared
      with ChIP-seq analyses. Using this approach, CENP-A(Cnp1) levels at fission yeast
      (S. pombe) centromeres were followed as they change during the cell cycle. Our
      measurements show that CENP-A(Cnp1) is deposited solely during the G2 phase of
      the cell cycle.

PMID- 22870389
TI  - Accelerated simulation of unfolding and refolding of a large single chain
      globular protein.
AB  - We have developed novel strategies for contracting simulation times in protein
      dynamics that enable us to study a complex protein with molecular weight in
      excess of 34 kDa. Starting from a crystal structure, we produce unfolded and then
      refolded states for the protein. We then compare these quantitatively using both
      established and new metrics for protein structure and quality checking. These
      include use of the programs Concoord and Darvols. Simulation of protein-folded
      structure well beyond the molten globule state and then recovery back to the
      folded state is itself new, and our results throw new light on the protein
      folding process. We accomplish this using a novel cooling protocol developed for
      this work.

PMID- 22870390
TI  - Systems analysis of transcription factor activities in environments with stable
      and dynamic oxygen concentrations.
AB  - Understanding gene regulation requires knowledge of changes in transcription
      factor (TF) activities. Simultaneous direct measurement of numerous TF activities
      is currently impossible. Nevertheless, statistical approaches to infer TF
      activities have yielded non-trivial and verifiable predictions for individual
      TFs. Here, global statistical modelling identifies changes in TF activities from
      transcript profiles of Escherichia coli growing in stable (fixed oxygen
      availabilities) and dynamic (changing oxygen availability) environments. A core
      oxygen-responsive TF network, supplemented by additional TFs acting under
      specific conditions, was identified. The activities of the cytoplasmic oxygen
      responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even
      on the scale of the bacterial cell, spatial effects significantly influence
      oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance
      in aerobic to anaerobic and anaerobic to aerobic transitions. One of these
      transcripts, ndh, encodes a major component of the aerobic respiratory chain and
      is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated
      that ArcA and FNR behaviour could not explain the ndh transcript profile, leading
      to the identification of another TF, PdhR, as the source of the asymmetry. Thus,
      this approach illustrates how systematic examination of regulatory responses in
      stable and dynamic environments yields new mechanistic insights into adaptive
      processes.

PMID- 22870391
TI  - Abscission checkpoint control: stuck in the middle with Aurora B.
AB  - At the end of cell division, the cytoplasmic bridge joining the daughter cells is
      severed through a process that involves scission of the plasma membrane. The
      presence of chromatin bridges 'stuck' in the division plane is sensed by the
      chromosomal passenger complex (CPC) component Aurora B kinase, triggering a
      checkpoint that delays abscission until the chromatin bridges have been resolved.
      Recent work has started to shed some light on the molecular mechanism by which
      the CPC controls the timing of abscission.

PMID- 22870392
TI  - AdpA, key regulator for morphological differentiation regulates bacterial
      chromosome replication.
AB  - AdpA, one of the most pleiotropic transcription regulators in bacteria, controls
      expression of several dozen genes during Streptomyces differentiation. Here, we
      report a novel function for the AdpA protein: inhibitor of chromosome replication
      at the initiation stage. AdpA specifically recognizes the 5' region of the
      Streptomyces coelicolor replication origin (oriC). Our in vitro results show that
      binding of AdpA protein decreased access of initiator protein (DnaA) to the oriC
      region. We also found that mutation of AdpA-binding sequences increased the
      accessibility of oriC to DnaA, which led to more frequent replication and
      acceleration of Streptomyces differentiation (at the stage of aerial hyphae
      formation). Moreover, we also provide evidence that AdpA and DnaA proteins
      compete for oriC binding in an ATP-dependent manner, with low ATP levels causing
      preferential binding of AdpA, and high ATP levels causing dissociation of AdpA
      and association of DnaA. This would be consistent with a role for ATP levels in
      determining when aerial hyphae emerge.

PMID- 22870393
TI  - Structural analysis of the human SYCE2-TEX12 complex provides molecular insights
      into synaptonemal complex assembly.
AB  - The successful completion of meiosis is essential for all sexually reproducing
      organisms. The synaptonemal complex (SC) is a large proteinaceous structure that
      holds together homologous chromosomes during meiosis, providing the structural
      framework for meiotic recombination and crossover formation. Errors in SC
      formation are associated with infertility, recurrent miscarriage and aneuploidy.
      The current lack of molecular information about the dynamic process of SC
      assembly severely restricts our understanding of its function in meiosis. Here,
      we provide the first biochemical and structural analysis of an SC protein
      component and propose a structural basis for its function in SC assembly. We show
      that human SC proteins SYCE2 and TEX12 form a highly stable, constitutive
      complex, and define the regions responsible for their homotypic and heterotypic
      interactions. Biophysical analysis reveals that the SYCE2-TEX12 complex is an
      equimolar hetero-octamer, formed from the association of an SYCE2 tetramer and
      two TEX12 dimers. Electron microscopy shows that biochemically reconstituted
      SYCE2-TEX12 complexes assemble spontaneously into filamentous structures that
      resemble the known physical features of the SC central element (CE). Our findings
      can be combined with existing biological data in a model of chromosome synapsis
      driven by growth of SYCE2-TEX12 higher-order structures within the CE of the SC.

PMID- 22870394
TI  - Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families
      in the vertebrates.
AB  - 14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of
      phosphorylated residues on target proteins. The present study shows that the
      human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which
      are proteins in families of two to four members that were generated by two rounds
      of whole genome duplication at the origin of the vertebrates. We identify 2R
      ohnologue families whose members share a 'lynchpin', defined as a 14-3-3-binding
      phosphosite that is conserved across members of a given family, and aligns with a
      Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example,
      the human receptor expression enhancing protein (REEP) 1-4 family has the
      commonest type of lynchpin motif in current datasets, with a phosphorylatable
      serine in the -2 position relative to the 14-3-3-binding phosphosite. In
      contrast, the second 14-3-3-binding sites of REEPs 1-4 differ and are
      phosphorylated by different kinases, and hence the REEPs display different
      affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular
      regulation involving protein families whose evolution into signal multiplexing
      systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom
      for other regulatory sites to evolve. While increased signalling complexity was
      needed for vertebrate life, these systems also generate vulnerability to genetic
      disorders.

PMID- 22870395
TI  - Development of a 10,000 locus genetic map of the sunflower genome based on
      multiple crosses.
AB  - Genetic linkage maps have the potential to facilitate the genetic dissection of
      complex traits and comparative analyses of genome structure, as well as molecular
      breeding efforts in species of agronomic importance. Until recently, the majority
      of such maps was based on relatively low-throughput marker technologies, which
      limited marker density across the genome. The availability of high-throughput
      genotyping technologies has, however, made possible the efficient development of
      high-density genetic maps. Here, we describe the analysis and integration of
      genotypic data from four sunflower (Helianthus annuus L.) mapping populations to
      produce a consensus linkage map of the sunflower genome. Although the individual
      maps (which contained 3500-5500 loci each) were highly colinear, we observed
      localized variation in recombination rates in several genomic regions. We also
      observed several gaps up to 26 cM in length that completely lacked mappable
      markers in individual crosses, presumably due to regions of identity by descent
      in the mapping parents. Because these regions differed by cross, the consensus
      map of 10,080 loci contained no such gaps, clearly illustrating the value of
      simultaneously analyzing multiple mapping populations.

PMID- 22870396
TI  - A genome-wide screen identifies genes that affect somatic homolog pairing in
      Drosophila.
AB  - In Drosophila and other Dipterans, homologous chromosomes are in close contact in
      virtually all nuclei, a phenomenon known as somatic homolog pairing. Although
      homolog pairing has been recognized for over a century, relatively little is
      known about its regulation. We performed a genome-wide RNAi-based screen that
      monitored the X-specific localization of the male-specific lethal (MSL) complex,
      and we identified 59 candidate genes whose knockdown via RNAi causes a change in
      the pattern of MSL staining that is consistent with a disruption of X-chromosomal
      homolog pairing. Using DNA fluorescent in situ hybridization (FISH), we confirmed
      that knockdown of 17 of these genes has a dramatic effect on pairing of the 359
      bp repeat at the base of the X. Furthermore, dsRNAs targeting Pr-set7, which
      encodes an H4K20 methyltransferase, cause a modest disruption in somatic homolog
      pairing. Consistent with our results in cultured cells, a classical mutation in
      one of the strongest candidate genes, pebble (pbl), causes a decrease in somatic
      homolog pairing in developing embryos. Interestingly, many of the genes
      identified by our screen have known roles in diverse cell-cycle events,
      suggesting an important link between somatic homolog pairing and the choreography
      of chromosomes during the cell cycle.

PMID- 22870397
TI  - Mutations in the pqe-1 gene enhance transgene expression in Caenorhabditis
      elegans.
AB  - Although various genetic tools have been developed and used as transgenes, the
      expression of the transgenes often is hampered by negative regulators. Disrupting
      such negative regulators of gene expression is potentially a way to overcome the
      common problem of low expression of transgenes. To find such regulators whose
      mutations enhance transgene expression in Caenorhabditis elegans, we took
      advantage of a newly developed reporter transgene, lin-11pADelta::venus. This
      transgene induces expression of a fluorescent protein, Venus, in specific neurons
      including AIZ, where the expression was stochastic. The frequency of reporter
      expression in AIZ seemed to be correlated with the strength of transgene
      expression. By using this system, in which a moderate increase of expression was
      converted to all-or-none expression states, we describe here a forward genetic
      screen for mutations that enhance the expression of transgenes. Through the
      screen, we found that mutations in the pqe-1 gene, which encodes a Q/P-rich
      nuclear protein with an exonuclease domain, increase the chance of reporter
      expression in AIZ. The fluorescence intensity in RIC, in which all lin
      11pADelta::venus animals show reporter expression, was increased in pqe-1
      mutants, suggesting that pqe-1 reduces the expression level of the transgene.
      Expression of transgenes with other promoters, 3'UTR, or reporter genes was also
      enhanced by the pqe-1 mutation, suggesting that the effect was not specific to a
      particular type of transgenes, whereas the effect did not seem to extend to
      endogenous genes. We propose that pqe-1 mutants can be used to increase the
      expression of various useful transgenes.

PMID- 22870398
TI  - A noncomplementation screen for quantitative trait alleles in saccharomyces
      cerevisiae.
AB  - Both linkage and linkage disequilibrium mapping provide well-defined approaches
      to mapping quantitative trait alleles. However, alleles of small effect are
      particularly difficult to refine to individual genes and causative mutations.
      Quantitative noncomplementation provides a means of directly testing individual
      genes for quantitative trait alleles in a fixed genetic background. Here, we
      implement a genome-wide noncomplementation screen for quantitative trait alleles
      that affect colony color or size by using the yeast deletion collection. As proof
      of principle, we find a previously known allele of CYS4 that affects colony color
      and a novel allele of CTT1 that affects resistance to hydrogen peroxide. To
      screen nearly 4700 genes in nine diverse yeast strains, we developed a high
      throughput robotic plating assay to quantify colony color and size. Although we
      found hundreds of candidate alleles, reciprocal hemizygosity analysis of a select
      subset revealed that many of the candidates were false positives, in part the
      result of background-dependent haploinsufficiency or second-site mutations within
      the yeast deletion collection. Our results highlight the difficulty of
      identifying small-effect alleles but support the use of noncomplementation as a
      rapid means of identifying quantitative trait alleles of large effect.

PMID- 22870400
TI  - Genetic diversity and population structure of Chinese foxtail millet [Setaria
      italica (L.) Beauv.] landraces.
AB  - As an ancient cereal of great importance for dryland agriculture even today,
      foxtail millet (Setaria italica) is fast becoming a new plant genomic model crop.
      A genotypic analysis of 250 foxtail millet landraces, which represent 1% of
      foxtail millet germplasm kept in the Chinese National Gene Bank (CNGB), was
      conducted with 77 SSRs covering the foxtail millet genome. A high degree of
      molecular diversity among the landraces was found, with an average of 20.9
      alleles per locus detected. STRUCTURE, neighbor-jointing, and principal
      components analyses classify the accessions into three clusters (topmost
      hierarchy) and, ultimately, four conservative subgroups (substructuring within
      the topmost clusters) in total, which are in good accordance with eco
      geographical distribution in China. The highest subpopulation diversity was
      identified in the accessions of Pop3 from the middle regions of the Yellow River,
      followed by accessions in Pop1 from the downstream regions of the Yellow River,
      suggesting that foxtail millet was domesticated in the Yellow River drainage area
      first and then spread to other parts of the country. Linkage disequilibrium (LD)
      decay of less than 20 cM of genetic distance in the foxtail millet landrace
      genome was observed, which suggests that it could be possible to achieve
      resolution down to the 20 cM level for association mapping.

PMID- 22870401
TI  - Genotype by environment interaction of quantitative traits: a case study in
      barley.
AB  - Genotype by environment interaction is a phenomenon that a better genotype in one
      environment may perform poorly in another environment. When the genotype refers
      to a quantitative trait locus (QTL), this phenomenon is called QTL by environment
      interaction, denoted by Q*E. Using a recently developed new Bayesian method and
      genome-wide marker information, we estimated and tested QTL main effects and Q*E
      interactions for a well-known barley dataset produced by the North American
      Barley Genome Mapping Project. This dataset contained seven quantitative traits
      collected from 145 doubled-haploid (DH) lines evaluated in multiple environments,
      which derived from a cross between two Canadian two-row barley lines, Harrington
      and TR306. Numerous main effects and Q*E interaction effects have been detected
      for all seven quantitative traits. However, main effects seem to be more
      important than the Q*E interaction effects for all seven traits examined. The
      number of main effects detected varied from 26 for the maturity trait to 75 for
      the heading trait, with an average of 61.86. The heading trait has the most
      detected effects, with a total of 98 (75 main, 29 Q*E). Among the 98 effects, 6
      loci had both the main and Q*E effects. Among the total number of detected loci,
      on average, 78.5% of the loci show the main effects whereas 34.9% of the loci
      show Q*E interactions. Overall, we detected many loci with either the main or the
      Q*E effects, and the main effects appear to be more important than the Q*E
      interaction effects for all the seven traits. This means that most detected loci
      have a constant effect across environments. Another discovery from this analysis
      is that Q*E interaction occurs independently, regardless whether the locus has
      main effects.

PMID- 22870399
TI  - Impact of loci nature on estimating recombination and mutation rates in Chlamydia
      trachomatis.
AB  - The knowledge of the frequency and relative weight of mutation and recombination
      events in evolution is essential for understanding how microorganisms reach
      fitted phenotypes. Traditionally, these evolutionary parameters have been
      inferred by using data from multilocus sequence typing (MLST), which is known to
      have yielded conflicting results. In the near future, these estimations will
      certainly be performed by computational analyses of full-genome sequences.
      However, it is not known whether this approach will yield accurate results as
      bacterial genomes exhibit heterogeneous representation of loci categories, and it
      is not clear how loci nature impacts such estimations. Therefore, we assessed how
      mutation and recombination inferences are shaped by loci with different genetic
      features, using the bacterium Chlamydia trachomatis as the study model. We found
      that loci assigning a high number of alleles and positively selected genes
      yielded nonconvergent estimates and incongruent phylogenies and thus are more
      prone to confound algorithms. Unexpectedly, for the model under evaluation,
      housekeeping genes and noncoding regions shaped estimations in a similar manner,
      which points to a nonrandom role of the latter in C. trachomatis evolution.
      Although the present results relate to a specific bacterium, we speculate that
      microbe-specific genomic architectures (such as coding capacity, polymorphism
      dispersion, and fraction of positively selected loci) may differentially buffer
      the effect of the confounding factors when estimating recombination and mutation
      rates and, thus, influence the accuracy of using full-genome sequences for such
      purpose. This putative bias associated with in silico inferences should be taken
      into account when discussing the results obtained by the analyses of full-genome
      sequences, in which the "one size fits all" approach may not be applicable.

PMID- 22870402
TI  - Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43
      and its overexpression reveals primarily nonreciprocal and nonoverlapping gene
      expression changes in the central nervous system of Drosophila.
AB  - The human Tar-DNA binding protein, TDP-43, is associated with amyotrophic lateral
      sclerosis (ALS) and other neurodegenerative disorders. TDP-43 contains two
      conserved RNA-binding motifs and has documented roles in RNA metabolism,
      including pre-mRNA splicing and repression of transcription. Here, using
      Drosophila melanogaster as a model, we generated loss-of-function and
      overexpression genotypes of Tar-DNA binding protein homolog (TBPH) to study their
      effect on the transcriptome of the central nervous system (CNS). By using
      massively parallel sequencing methods (RNA-seq) to profile the CNS, we find that
      loss of TBPH results in widespread gene activation and altered splicing, much of
      which are reversed by rescue of TBPH expression. Conversely, TBPH overexpression
      results in decreased gene expression. Although previous studies implicated both
      absence and mis-expression of TDP-43 in ALS, our data exhibit little overlap in
      the gene expression between them, suggesting that the bulk of genes affected by
      TBPH loss-of-function and overexpression are different. In combination with
      computational approaches to identify likely TBPH targets and orthologs of
      previously identified vertebrate TDP-43 targets, we provide a comprehensive
      analysis of enriched gene ontologies. Our data suggest that TDP-43 plays a role
      in synaptic transmission, synaptic release, and endocytosis. We also uncovered a
      potential novel regulation of the Wnt and BMP pathways, many of whose targets
      appear to be conserved.

PMID- 22870403
TI  - Impact of sampling schemes on demographic inference: an empirical study in two
      species with different mating systems and demographic histories.
AB  - Most species have at least some level of genetic structure. Recent simulation
      studies have shown that it is important to consider population structure when
      sampling individuals to infer past population history. The relevance of the
      results of these computer simulations for empirical studies, however, remains
      unclear. In the present study, we use DNA sequence datasets collected from two
      closely related species with very different histories, the selfing species
      Capsella rubella and its outcrossing relative C. grandiflora, to assess the
      impact of different sampling strategies on summary statistics and the inference
      of historical demography. Sampling strategy did not strongly influence the mean
      values of Tajima's D in either species, but it had some impact on the variance.
      The general conclusions about demographic history were comparable across sampling
      schemes even when resampled data were analyzed with approximate Bayesian
      computation (ABC). We used simulations to explore the effects of sampling scheme
      under different demographic models. We conclude that when sequences from modest
      numbers of loci (<60) are analyzed, the sampling strategy is generally of limited
      importance. The same is true under intermediate or high levels of gene flow (4Nm
      > 2-10) in models in which global expansion is combined with either local
      expansion or hierarchical population structure. Although we observe a less severe
      effect of sampling than predicted under some earlier simulation models, our
      results should not be seen as an encouragement to neglect this issue. In general,
      a good coverage of the natural range, both within and between populations, will
      be needed to obtain a reliable reconstruction of a species's demographic history,
      and in fact, the effect of sampling scheme on polymorphism patterns may itself
      provide important information about demographic history.

PMID- 22870404
TI  - A sequence-anchored linkage map of the plant-parasitic nematode Meloidogyne hapla
      reveals exceptionally high genome-wide recombination.
AB  - Root-knot nematodes (Meloidogyne spp.) cause major yield losses to many of the
      world's crops, but efforts to understand how these pests recognize and interact
      with their hosts have been hampered by a lack of genetic resources. Starting with
      progeny of a cross between inbred strains (VW8 and VW9) of Meloidogyne hapla that
      differed in host range and behavioral traits, we exploited the novel, facultative
      meiotic parthenogenic reproductive mode of this species to produce a genetic
      linkage map. Molecular markers were derived from SNPs identified between the
      sequenced and annotated VW9 genome and de novo sequence of VW8. Genotypes were
      assessed in 183 F2 lines. The colinearity of the genetic and physical maps
      supported the veracity of both. Analysis of local crossover intervals revealed
      that the average recombination rate is exceptionally high compared with that in
      other metazoans. In addition, F2 lines are largely homozygous for markers
      flanking crossover points, and thus resemble recombinant inbred lines. We suggest
      that the unusually high recombination rate may be an adaptation to generate
      within-population genetic diversity in this organism. This work presents the most
      comprehensive linkage map of a parasitic nematode to date and, together with
      genomic and transcript sequence resources, empowers M. hapla as a tractable
      model. Alongside the molecular map, these progeny lines can be used for analyses
      of genome organization and the inheritance of phenotypic traits that have key
      functions in modulating parasitism, behavior, and survival and for the eventual
      identification of the responsible genes.

PMID- 22870405
TI  - Evolutionary recovery of a recombinant viral genome.
AB  - It is well appreciated that the evolutionary divergence of genes and genomes from
      a common ancestor ultimately leads to incompatibilities if those genomes are
      hybridized. Far less is known about the ability and nature of compensatory
      evolution to yield the recovery of function in hybrid genomes. Here the major
      capsid gene of the bacteriophage T7 (40-kb dsDNA) was replaced with the
      homologous gene of either T3 or K11, each 22% different at the protein level from
      the T7 homolog. Initial fitness was moderately impaired for the T3 exchange, but
      the K11 exchange was not viable without a compensatory change in the T7
      scaffolding protein. Subsequent adaptation of the transgenic phages led to nearly
      complete fitness recoveries. Compensatory changes were few, mostly in the
      transgene and its main interacting partner, the scaffolding protein gene. The
      large magnitude of fitness recovery with relatively few mutations suggests that
      the fitness costs of hybridizations and horizontal gene exchanges between
      moderately diverged genomes can potentially be short-lived through compensatory
      evolution.

PMID- 22870407
TI  - A new era for the Journal of Family and Community Medicine.
AB  - The Journal of Family and Community Medicine (JFCM) is the official scientific
      publication of the Saudi Society of Family and Community Medicine (SSFCM). The
      JFCM was first published in 1994 to meet "...a pressing need for a medical
      journal that would develop into a forum to address certain issues of family and
      community medicine."[1] Thanks to the efforts of the earlier editorial team, the
      journal continued to serve as a major source for research in the field of family
      and community medicine and helped many researchers to communicate their work with
      the scientific communities. These results were achieved in spite of many
      obstacles that faced the JFCM at its early years. Now, thanks to the efforts of
      the new editorial team and the continued support of the University of Dammam and
      the sponsors of the SSFCM, the JFCM is an international peer-reviewed journal.
      The journal is committed to relevance and excellence and has a clear vision
      "...of becoming a leader in medical journalism in the field of family and
      community medicine..."[2]

PMID- 22870406
TI  - Interactions between the kinetochore complex and the protein kinase A pathway in
      Saccharomyces cerevisiae.
AB  - The kinetochore is a large structure composed of multiple protein subcomplexes
      that connect chromosomes to spindle microtubules to enable accurate chromosome
      segregation. Significant advances have been made in the identification of
      kinetochore proteins and elucidation of kinetochore structure; however,
      comparatively little is known about how cellular signals integrate with
      kinetochore function. In the budding yeast Saccharomyces cerevisiae, the cyclic
      AMP protein kinase A signaling pathway promotes cellular growth in response to
      glucose. In this study, we find that decreasing protein kinase A activity, either
      by overexpressing negative regulators of the pathway or deleting the upstream
      effector Ras2, improves the viability of ipl1 and spc24 kinetochore mutants.
      Ipl1/Aurora B is a highly conserved kinase that corrects attachment of sister
      kinetochores that have attached to the same spindle pole, whereas Spc24 is a
      component of the conserved Ndc80 kinetochore complex that attaches directly to
      microtubules. Unexpectedly, we find that kinetochore mutants have increased
      phosphorylation levels of protein kinase A substrates, suggesting that the cyclic
      AMP protein kinase A signaling pathway is stimulated. The increase in protein
      kinase A activity in kinetochore mutants is not induced by activation of the
      spindle checkpoint or a metaphase delay because protein kinase A activity remains
      constant during an unperturbed cell cycle. Finally, we show that lowering protein
      kinase A activity can rescue the chromosome loss defect of the inner kinetochore
      ndc10 mutant. Overall, our data suggest that the increased protein kinase A
      activity in kinetochore mutants is detrimental to cellular growth and chromosome
      transmission fidelity.

PMID- 22870408
TI  - Clinical effect of Metformin in children and adolescents with type 2 diabetes
      mellitus: a systematic review and meta-analysis.
AB  - To assess the clinical value and of metformin as mono-therapy versus other
      treatments for type 2 diabetes mellitus in children and adolescents. Major
      electronic databases, the reference lists of relevant articles and databases of
      ongoing trials were searched. Authors of reviews and metformin manufacturers were
      contacted in order to obtain more references and reports of unpublished trials.
      The methodological quality of these reports, included randomised controlled
      trials (RCTs) was assessed using the National Health System Centre for Reviews
      and Dissemination (NHS CRD) checklist. The search identified 1,825 studies. Three
      RCTs met the inclusion criteria. Two RCTs had been completed and one was still
      ongoing. In the metformin group there were significant reductions of mean change
      of HBA1c from baseline. It reduced by -0.71% (P = 0.0002) and in the other trial
      the result was reduced by -1.10 (95% CI: -1.19 to -1.01). In addition, more
      patients (48.1%) in the metformin group achieved good glycaemic control (<7%) at
      week 24. The mean changes in FPG from baseline were significantly (P < 0.05)
      different in the metformin group (-16.6%, for week 18 and week 24 20.6%. In the
      second trial there was a significant (P < 0.001) reduction in the adjusted mean
      of FPG from baseline in the metformin group, while there was an increase in the
      placebo group ( -42.9 mg/dl vs. +21.4mg/dl) with mean difference of -64.80 in
      favour of the metformin group. For BMI, significant (P < 0.001) differences were
      seen at week 12 and week 24 (0.07 and 0.55 kg(2)) for metformin and glimepiride
      respectively. There was no significant difference between the placebo and
      metformin in the other trials. For lipid value there was a significant decrease
      in LDL levels in the metformin group. No significant changes were found in the
      other lipid parameters after adjusting. There were more adverse events in the
      metformin group but they were not statistically significant. There was a limited
      but not convincing evidence to suggest that metformin can improve the glycaemic
      control in children and adolescent with type 2 diabetes compared with other
      interventions. This is may be the result of the limited number, poor quality and
      short duration of the included trials.

PMID- 22870409
TI  - The attitude of health care professionals towards accreditation: A systematic
      review of the literature.
AB  - Accreditation is usually a voluntary program, in which authorized external peer
      reviewers evaluate the compliance of a health care organization with pre
      established performance standards. The aim of this study was to systematically
      review the literature of the attitude of health care professionals towards
      professional accreditation. A systematic search of four databases including
      Medline, Embase, Healthstar, and Cinhal presented seventeen studies that had
      evaluated the attitudes of health care professionals towards accreditation.
      Health care professionals had a skeptical attitude towards accreditation. Owners
      of hospitals indicated that accreditation had the potential of being used as a
      marketing tool. Health care professionals viewed accreditation programs as
      bureaucratic and demanding. There was consistent concern, especially in
      developing countries, about the cost of accreditation programs and their impact
      on the quality of health care services.

PMID- 22870410
TI  - Effectiveness of physical activity promotion in blood pressure and blood sugar
      reduction: a community-based intervention study in rural south India.
AB  - CONTEXT: Physical activity of moderate intensity for 30 minutes a day, on most
      days substantially reduces the risk of many chronic diseases. AIM: To assess the
      effect of regular physical activity on blood pressure and blood sugar levels in a
      rural Indian community SETTINGS AND DESIGN: This community-based study was
      carried out in Periakattupalayam and Rangareddipalayam in south India, with 485
      subjects, aged 20 to 49 years. MATERIALS AND METHODS: THE STUDY WAS DONE IN FIVE
      PHASES: Awareness campaign, baseline assessment of participants, intervention
      phase (10 weeks), interim, and final assessment. Physical activity of moderate
      intensity (brisk walking for 30 minutes on four days / week) was promoted by
      forming 30 small walking groups, in a home-based setting, with professional
      supervision. Village leaders and Self-Help Group members were the resource people
      for the promotion of physical activity. STATISTICAL ANALYSIS: Analysis was done
      by using paired 't' test; the 'Intention-to-Treat' approach was utilized for the
      interpretation of the findings of the study. RESULTS: Of the 485 subjects, 265
      (54.6%) complied with walking on more than four days / week, while 156 (32.2%)
      walked on one to four days / week, and 64 (13.2%) dropped out during the
      intervention period. This study has shown that a 10-week intervention to promote
      physical activity was effective in significantly decreasing the population's BP
      by 1.56 / 0.74 mm Hg, fasting blood sugar levels by 2.82 mg%, body weight by 0.17
      kg, and BMI by 0.06 kg / m(2). CONCLUSIONS: This study has proved the functional
      feasibility of enabling people to undertake physical activity in a rural Indian
      community, and the effectiveness of using physical activity, to significantly
      reduce the population's mean BP and blood sugar levels.

PMID- 22870411
TI  - Predictors of pulmonary involvement in patients with extra-pulmonary
      tuberculosis.
AB  - OBJECTIVES: The aim of this study is to assess the value of chest radiographs
      (CXRs) and sputum examinations in detecting pulmonary involvement of tuberculosis
      (TB) in patients with extra-pulmonary tuberculosis (EPTB). MATERIALS AND METHODS:
      A retrospective analysis was performed among 248 EPTB patients with culture
      proven diagnosis of tuberculosis seen between January 2001 and December 2007 at a
      tertiary teaching hospital, Riyadh, Saudi Arabia. Demographics, clinical,
      laboratory and radiological findings were reviewed and assessed. This study was
      approved by the hospital ethics and research committee. RESULTS: One hundred
      twenty five of 233 EPTB patients (53.6%) had abnormal CXR findings. There was a
      significant difference in the occurrence of positive sputum culture results
      between patients with abnormal CXR findings (30/57) and those with normal CXR
      findings (4/17) (P = 0.04). Of 17 HIV-negative/unknown HIV-status EPTB patients
      with normal CXR results, 4 patients (23.5%) had positive sputum culture results.
      Intrathoracic lymphadenopathy (P < 0.001), pleural TB (P < 0. 001) and
      disseminated TB (P = 0.004) were associated with an increased risk of abnormal
      CXR findings. Patients with cough (52.9%), weight loss (41.2%) and night sweats
      (26.5%) are more likely to have positive sputum culture results. CONCLUSION: CXR
      findings are predictive of positive sputum culture results. However, the rate of
      normal CXR among EPTB patients with positive sputum culture results was
      relatively high. Therefore, respiratory specimen cultures should be obtained in
      TB suspects with a normal CXR to identify potentially infectious cases of TB.

PMID- 22870412
TI  - Knowledge and attitude of health professionals in the Riyadh region, Saudi
      Arabia, toward complementary and alternative medicine.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is a popular treatment
      option for many populations. The present work is aimed at studying the knowledge
      and attitude of health professionals in the Riyadh region, Saudi Arabia, toward
      CAM. MATERIAL AND METHODS: In this cross-sectional survey, a multistage random
      sample was taken from health professionals working in hospitals in Riyadh city
      and surrounding governorates. Data were collected through a self-administered
      questionnaire, from 306 health professionals working in 19 hospitals, on socio
      demographic data, knowledge about CAM and their sources, and attitudes toward CAM
      practices. RESULTS: Of the participants, 88.9% had some knowledge about CAM.
      Respondents with a doctorate degree (94.74%) and 92.53% of those with a
      bachelor's degree had significantly higher knowledge of CAM than subjects with a
      diploma, a fellowship, or a master's degree (68.75%, 76.67%, and 85.41%,
      respectively, P = 0.004). Mass media represented 60.1% of sources of the
      knowledge of CAM followed by family, relatives, and friends (29.08%) and health
      educational organizations (14.71%). Participants estimated that prophetic
      medicine including prayer, honey and bee products, medical herbs, Hijama,
      nutrition and nutritional supplements, cauterization, and camel milk and urine
      were the most commonly used CAM practices (90.5%, 85%, 76.9%, 70.6%, 61.4%,
      55.9%, and 52.5%, respectively) in addition to medical massage (61.8%) and
      acupuncture (55%). One hundred and fifteen (80%) physicians were ready to talk
      with their patients on CAM. CONCLUSION: The willingness to improve knowledge and
      create a positive attitude in health professionals toward CAM has increased.
      Religious practices, especially those related to prophetic medicine, are more
      common in the region. Health educational organizations have to play a greater
      role by being the source of evidence-based knowledge of CAM. Talking on CAM with
      patients should be improved by rooting them on evidence-based practices.

PMID- 22870413
TI  - The status of Vitamin D in medical students in the preclerkship years of a Saudi
      medical school.
AB  - BACKGROUND: The prevalence of vitamin D deficiency has recently been recognized
      in different parts of the world, even affecting healthy populations. The
      deficiency of vitamin D can lead to rickets in children and osteomalacia in
      adults. Few studies have been done to evaluate the status of vitamin D in the
      medical community. The objective of this study was to evaluate the prevalence of
      low levels of vitamin D in healthy Saudi medical students. MATERIALS AND METHODS:
      A cross-sectional study was carried out in November 2009 on male and female
      students in the preclerkship years of medical school at the King Faisal
      University, Dammam. Data on age, consumption of dairy products and seafood, and
      exposure to sunlight were collected. The body mass index was calculated.
      Approximately, 15 ml of blood was extracted for the measurement of serum calcium,
      serum albumin, serum phosphorus, alkaline phosphatase, fasting parathyroid
      hormone, and vitamin D levels. Vitamin D deficiency was defined as serum 25
      hydroxy vitamin D < 50 nmol/l. Comparison between groups was done for statistical
      significance using an unpaired t-test. Significance was set at P < 0.05 using 95%
      CI for all comparisons. RESULTS: The data from 95 male and 103 female students
      were analyzed. The mean age for all students was 19.54 years. In 100% of the
      students, the vitamin D level was low. The prevalence of vitamin D deficiency in
      all students was 96.0% (92.64% in males and 99.03% in females), while the
      remaining 4% had vitamin D insufficiency. The mean 25-hydroxy vitamin D level was
      26.83 +/- 12.60 nmol/l in males and 16.03 +/- 8.28 nmol/l in females (P-value =
      0.0001). Males had a statistically significant higher body mass index as well as
      consumption of dairy products, while the consumption of seafood was significantly
      higher in females. There was no difference between the two groups in terms of
      exposure to the sun. CONCLUSION: Vitamin D deficiency was highly prevalent among
      medical students included in this study. An urgent action has to be taken in
      order to prevent adverse consequences of low vitamin D in the young, otherwise
      healthy populations.

PMID- 22870414
TI  - Pre-hypertension and hypertension in college students in Kuwait: a neglected
      issue.
AB  - OBJECTIVE: To determine the proportion of pre-hypertension and hypertension in
      college students in Kuwait and their related risk factors. MATERIALS AND METHODS:
      A total of 803, randomly selected students aged 17 to 23 years (346 male, 457
      female) from different colleges in Kuwait, were included in the study between
      2009 and 2010. Systolic and diastolic blood pressure measurements were taken by
      trained personnel. Pre-hypertension was defined as systolic pressure between 120
      and 139 mm Hg or diastolic pressure between 80 and 89 mm Hg. Risk factor
      measurements that were determined, included smoking, body mass index (BMI), and
      family history of hypertension. Blood samples were collected and impaired glucose
      tolerance (IGT) and lipid profile levels were determined. RESULTS: There were no
      hypotensive students. Normotensives constituted 53.5% (n = 430), pre
      hypertensives formed 39.5% (n = 317), and hypertensive students comprised of 7%
      (n = 56). The overall proportions of hypertension and pre-hypertension were
      higher among male students (85.7 and 64.4%) than female students (14.3 and
      35.6%), respectively. Hypertensive and pre-hypertensive students versus
      normotensive students had significantly higher levels of BMI-based obesity,
      smoking, glycated hemoglobin (HbA1c), and IGT. Also, hypertensive and pre
      hypertensive, compared to normotensive students, had significantly higher
      proportions (21.4, 18.3, and 4.0%, respectively) of risky high-density
      lipoprotein (HDL) level (< 1 mg / dL), cholesterol (7.1, 3.8, and 1.4%,
      respectively), and triglycerides (TG) (17.9, 9.1, and 7.9%, respectively) where p
      was< 0.001, 0.016, and 0.051, respectively. CONCLUSION: Hypertensive and pre
      hypertensive students showed elevated levels of lipids and BMI-based obesity more
      than normotensive students. TG, HDL, HbA1c, and cholesterol appeared to influence
      pre-hypertension.

PMID- 22870415
TI  - Maternal antecedents of infants with abnormal head sizes in southwest Nigeria: A
      community-based study.
AB  - OBJECTIVE: To identify the socio-demographic antecedents and pregnancy-related
      history of infants with abnormal head sizes in a developing country. MATERIALS
      AND METHODS: An observational study of mother-infant pairs attending routine
      immunization clinics in an inner-city community in Lagos, Nigeria. Age and gender
      specific head circumference was determined with the current Child Growth
      Standards of the World Health Organization (WHO). Factors independently
      associated with any abnormal head size (z-score < - 2SD or > 2SD), based on the
      adjusted odds ratio (OR) and 95% confidence interval (CI), were explored with
      multiple logistic regression analyses. RESULTS: Of the 5731 mothers studied, 730
      (12.7%) had an offspring with an abnormal head size. In the final regression
      model, teenage mothers (OR:1.86; CI:1.26 - 2.75), mothers with primary or no
      education (OR:1.65; P = 0.007), multiple pregnancies (OR:3.88; CI:2.53 - 5.95),
      and delivery in either private hospitals (OR:1.54; CI:1.22 - 1.95) or residential
      homes (OR:1.50; CI:1.05 - 2.14), compared to government hospitals, were
      significantly more likely to have offsprings with abnormal head sizes.
      CONCLUSIONS: Community-oriented public health education, targeting prospective
      mothers with multiple pregnancies, teenage girls, and women with little or no
      formal education on the potential risk of delivery outside public hospitals, may
      curtail the burden of abnormal head size of their offspring and reduce the
      pressure on the already overstretched rehabilitation services in resource-poor
      countries.

PMID- 22870416
TI  - Interpreting the psychometric properties of the components of primary care
      instrument in an elderly population.
AB  - OBJECTIVE: To determine the psychometric properties of the Components of Primary
      Care Instrument (CPCI) in a patient population aged 65 or older. MATERIALS AND
      METHODS: 795 participants in the OKLAHOMA Studies, a longitudinal population
      based study of predominantly Caucasian, elderly patients, completed the CPCI.
      Reliability analysis and confirmatory factor analysis were done to provide
      psychometric properties for this elderly sample. Models were constructed and
      tested to determine the best fit for the data including the addition of a method
      factor for negatively worded items. RESULTS: Cronbach's alphas were comparable to
      values reported in prior studies. The confirmatory factor analysis with factor
      inter-correlations and a method factor each improved the fit of the factor model
      to the data. The combined model's fit approached the level conventionally
      recognized as adequate. CONCLUSION: CPCI appears to be a reliable tool for
      describing patient perceptions of the quality of primary care for patients over
      age 65.

PMID- 22870418
TI  - Infant feeding practices in the rural population of north India.
AB  - BACKGROUND: Breastfeeding is one of the most important determinants of child
      survival, birth spacing, and the prevention of childhood infections. The
      beneficial effects of breastfeeding depend on its initiation, duration, and the
      age at which the breastfed child is weaned. Breastfeeding practices vary among
      different regions and communities. OBJECTIVES: To assess the pattern of infant
      feeding and its relation to certain practices of maternity and newborn care, and
      to assess the knowledge of mothers on the advantages of exclusive breastfeeding.
      MATERIALS AND METHODS: The cross-sectional study was carried out in randomly
      selected villages of the Bhojipura Block of Bareilly district, Uttar Pradesh. A
      total of 123 women who had delivered within the last year were interviewed in a
      house-to-house survey. A study instrument was used to collect data. Chi- square
      test and regression analysis were used to analyze the data. RESULTS: Most of the
      mothers were aged less than 30 years (78.04%) and were Hindus (73.9%). Most were
      illiterate (69.9%) and belonged to the lower socioeconomic class (97.5%). The
      majority were housewives (99.1%) and multiparous (68.2%). Most had initiated
      breastfeeding (78.8%) within 24 hours of delivery. About 15.4% of the infants did
      not receive colostrum and 22.8% of the infants were not exclusively breastfed.
      Ghutti (water mixed with honey and herbs), boiled water, tea, and animal milk
      were commonly used pre-lacteal feeds. About 47.2% of the respondents were not
      aware of the benefits of exclusive breastfeeding. About one quarter of the
      mothers started complementary feeding before the child was six months old. About
      half the deliveries had taken place at home and only a quarter of the females had
      had three or more antenatal visits during pregnancy. The birth weight of the
      majority (78%) of newborns was not measured. A majority (69.9%) of the mothers
      did not receive advice on child feeding. Multivariate logistic regression
      analysis showed that maternity and newborn care variables had no significant
      association with exclusive breastfeeding. CONCLUSIONS: Despite higher rates of
      early initiation of breastfeeding and exclusive breastfeeding, awareness of the
      benefits of exclusive breastfeeding was low. This indicates the need to promote
      awareness of the correct method of infant feeding and care of the newborn.
      Creating an awareness of the advantages of exclusive breastfeeding will further
      strengthen and support this common practice in rural communities and avoid an
      early introduction to complementary foods for sociocultural reasons.

PMID- 22870417
TI  - Pattern of self-medication with analgesics among Iranian University students in
      central Iran.
AB  - BACKGROUND: Self-medication is defined as the use of drugs for the treatment of
      self-diagnosed disorders. It is influenced by factors such as education, family,
      society, law, availability of drugs and exposure to advertisements. This study
      was performed to evaluate self-medication with analgesics and its pattern among
      different groups of Iranian University Students. MATERIALS AND METHODS: A
      randomized, cross-sectional, multicenter study was conducted from December 2009
      to February 2010. The target population of this study was 564 students out of
      10,000 students attending four medical and non-medical science universities in
      Qom state. Data was analyzed using SPSS version 16, and analysis was conducted
      with descriptive analysis procedures. RESULTS: 76.6% of the students had used
      analgesics in self-medication in the previous 3 months. The frequency of
      analgesic use in the study period was once in 19.2% of the participants, twice in
      22.2%, three times in 16.3% and more than three times in 35.5% of the
      participants, although 6.8% of them were not sure when they were used. Of all the
      respondents, 49.8% reported headache as the problem. This was the most common
      problem, after which came Dysmenorrhea,headache and stomach ache. Bone and joint
      pains were other problems that led to the use of analgesics. The most commonly
      used source of information for self-medication with analgesics was advice from
      friends and family (54.7%), previously prescribed medications (30.1%), their
      medical knowledge (13.3%) and recommendation of a pharmacist (1.9%). CONCLUSION:
      Self-medication with analgesics is very high among Iranian students in Qom city.
      This could be an index for other parts of the Iranian community. Because the
      source of information about analgesics is inappropriate, we would recommend
      education courses about analgesics and self-medication on the radio and
      television for the entire population.

PMID- 22870419
TI  - Integration of evidence based medicine into the clinical years of a medical
      curriculum.
AB  - Teaching Evidence Based Medicine (EBM) helps medical students to develop their
      decision making skills based on current best evidence, especially when it is
      taught in a clinical context. Few medical schools integrate Evidence Based
      Medicine into undergraduate curriculum, and those who do so, do it at the
      academic years only as a standalone (classroom) teaching but not at the clinical
      years. The College of Medicine at King Saud bin Abdulaziz University for Health
      Sciences was established in January 2004. The college adopted a four-year Problem
      Based Learning web-based curriculum. The objective of this paper is to present
      our experience in the integration of the EBM in the clinical phase of the medical
      curriculum. We teach EBM in 3 steps: first step is teaching EBM concepts and
      principles, second is teaching the appraisal and search skills, and the last step
      is teaching it in clinical rotations. Teaching EBM at clinical years consists of
      4 student-centered tutorials. In conclusion, EBM may be taught in a systematic,
      patient centered approach at clinical rounds. This paper could serve as a model
      of Evidence Based Medicine integration into the clinical phase of a medical
      curriculum.

PMID- 22870420
TI  - Hyercalcemia induced by interferon therapy in chronic hepatitis C.
AB  - Interferon is being increasingly used in the treatment of chronic hepatitis C.
      Several case reports have suggested an association between interferon therapy and
      sarcoidosis with hypercalcemia. We report a case of severe hypercalcemic crisis
      with bilateral hilar lymphadenopathy in a male patient who was receiving
      interferon therapy for hepatitis C. Gastroenterologists should be aware of this
      unusual but clinically important complication of interferon therapy.

PMID- 22870421
TI  - How NICE do we have to be? Lessons learned from the NICE experience.

PMID- 22870422
TI  - Editorial.

PMID- 22870423
TI  - Assessing adherence to teriparatide therapy, causes of nonadherence and effect of
      adherence on bone mineral density measurements in osteoporotic patients at high
      risk for fracture.
AB  - OBJECTIVES: To determine (a) adherence rates at 6, 9 and 18 months amongst
      patients receiving teriparatide treatment for severe osteoporosis and (b) causes
      of therapy discontinuation and the effect of teriparatide on bone mineral density
      (BMD) in adherent and nonadherent patients at different time intervals. METHODS:
      A retrospective chart review of 111 patients receiving teriparatide from
      September 2004 to June 2007 was performed. Patients self-reports were used to
      record adherence and causes of nonadherence at 6, 9 and 18 months. BMDs for all
      patients were measured using the same DXA scanner at baseline and follow up.
      RESULTS: Of 111 participants, 17 were male (mean age 60 years) and 94 were female
      (mean age 69 years). Of these, 12 did not initiate therapy and 4 were lost to
      follow up. Reported adherence was 89.6% at 6 months, 87.6% at 9 months and 74.7%
      at 18 months. Causes of nonadherence included cost (n = 4), no benefit (n = 1)
      and adverse events (n = 8). Common adverse events were leg cramps (n = 9),
      headache (n = 5) and myalgia (n = 4). Mean spine and femur BMD changes were 3.30%
      and 0.67% at 4-9 months respectively, and 5.39% and 0.77% at 10-18 months
      respectively. CONCLUSION: Adherence to teriparatide was almost 90% at 9 months
      and decreased to 75% at 18 months. Adverse events led to nonadherence in 20% of
      patients. Those who were nonadherent had lower baseline BMD values than those who
      were adherent. Changes in BMD at the lumbar spine were greater than changes
      observed at the femoral neck.

PMID- 22870424
TI  - Denosumab in postmenopausal osteoporosis: what the clinician needs to know.
AB  - Denosumab is a subcutaneously (SC) administered investigational fully human
      monoclonal antibody to receptor activator of nuclear factor-kB ligand (RANKL), a
      cytokine member of the tumor necrosis factor family that is the principal
      mediator of osteoclastic bone resorption. RANKL stimulates the formation,
      activity, and survival of osteoclasts, and is implicated in the pathogenesis of
      postmenopausal osteoporosis and other skeletal disorders associated with
      increased bone remodeling. Denosumab binds RANKL, preventing it from binding to
      RANK, thereby reducing the formation, activity, and survival of osteoclasts and
      slowing the rate of bone resorption. Postmenopausal women with low bone mineral
      density (BMD) treated with denosumab have a reduction of bone turnover markers
      and an increase in BMD that is rapid, sustained, and reversible. In
      postmenopausal women with osteoporosis, denosumab reduces the risk of vertebral,
      hip, and nonvertebral fractures. In postmenopausal women with low BMD randomized
      to receive denosumab or alendronate, denosumab is associated with a significantly
      greater increase in BMD and further reduction in bone turnover markers compared
      with alendronate. In postmenopausal women with low BMD who were previously
      treated with alendronate, those who switched to denosumab have a significantly
      greater BMD increase and further reduction in bone turnover markers compared with
      those continuing alendronate. Denosumab is well tolerated with a favorable safety
      profile. It is a promising emerging drug for the prevention and treatment of
      osteoporosis, offering a long dosing interval of every 6 months and convenient SC
      dosing, with the potential of improving long-term adherence to therapy compared
      with current oral treatments.

PMID- 22870425
TI  - Treatment of glucocorticoid-induced osteoporsis.
AB  - Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary
      osteoporosis. Fractures occur in 30-50% of patients with GIO. Therefore,
      treatment of this disease is critical. Although patients should receive
      supplemental calcium and vitamin D, additional measures are necessary to prevent
      fractures. Estrogens and androgens may be of value in patients with hypogonadism,
      but bisphosphonates and teriparatide are the most effective agents in the
      treatment of GIO. Bisphosphonates prevent the early bone loss that follows
      exposure to glucocorticoids, and which has been attributed to increased
      resorption. Teriparatide appears to be more effective than alendronate in
      established GIO when reduced bone formation is the predominant pathophysiological
      mechanism. In conclusion, GIO can be prevented and treated with appropriate
      medical intervention.

PMID- 22870427
TI  - NICE: Its Influence in Treating Osteoporosis in the UK and beyond.

PMID- 22870426
TI  - Focusing osteoarthritis management on modifiable risk factors and future
      therapeutic prospects.
AB  - The pathogenesis of osteoarthritis (OA) appears to be the result of a complex
      interplay between mechanical, cellular, and biochemical forces. Obesity is the
      strongest risk factor for disease onset and mechanical factors dominate the risk
      for disease progression. This narrative review focuses on the influence of
      biomechanics and obesity on the etiology of OA and its symptomatic presentation.
      We need to revisit the way we currently manage the disease and focus on the
      modifiable, primarily through nonpharmacologic intervention. Greater therapeutic
      attention to the important role of mechanical factors and obesity in OA
      etiopathogenesis is required if we are to find ways of reducing the public health
      impact of this condition.

PMID- 22870428
TI  - Febuxostat treatment for gout: what the clinician needs to know.
AB  - Febuxostat is a new non-purine based inhibitor of xanthine oxidase that will be a
      useful addition to the drugs available to treat gout. This short review covers
      general principles of the management of gout and then focuses on practical
      aspects and use of febuxostat.

PMID- 22870429
TI  - Glucocorticoid-induced osteoporosis: treatment update and review.
AB  - Glucocorticoid-induced osteoporosis (GIO) is a serious consequence of
      glucocorticoid therapy leading to fractures in 30-50% of patients. A wide range
      of protective medications have been studied in this condition including calcium,
      vitamin D, vitamin D analogs, oral and intravenous bisphosphonates, sex hormones,
      anabolic agents and calcitonin. The mechanism of action, and evidence for these
      therapies, are reviewed - focusing on important trials and new evidence. Recently
      published guidelines are also reviewed and compared. Bisphosphonates are
      currently the recommended first-line therapy for the prevention and treatment of
      GIO. They have been shown to increase bone mineral density (BMD) at the spine and
      hip and to decrease the incidence of vertebral fractures (especially in
      postmenopausal women). Testosterone therapy and female hormone replacement
      therapy (HRT) have been found to increase lumbar spine BMD in hypogonadal
      patients on glucocorticoid therapy, but effects on hip BMD have not been
      consistent and there is no fracture data in the GIO population. Similarly,
      calcitonin increases lumbar spine BMD but has no proven fracture efficacy. The
      effect of selective estrogen receptor modulators, the oral contraceptive pill and
      strontium on GIO is relatively unknown. Parathyroid hormone (PTH 1-34) and
      zoledronic acid have emerged as exciting new options for the treatment of GIO.
      Both therapies have been found to result in gains in BMD at the spine and hip
      that are either noninferior or superior to those seen with oral bisphosphonate
      therapy. PTH 1-34 has also been found to decrease the incidence of new vertebral
      fractures and may be an option in high-risk patients established on long-term
      glucocorticoid therapy.

PMID- 22870430
TI  - Advancing our understanding of osteocyte cell biology.
AB  - Osteocytes were the forgotten bone cell until the bone community could become
      convinced that these cells do serve an important role in bone function and
      maintenance. In this review we trace the history of osteocyte characterization
      and present some of the major observations that are leading to the conclusion
      that these cells are not passive placeholders residing in the bone matrix, but
      are indeed, major orchestrators of bone remodeling.

PMID- 22870431
TI  - Understanding Personalized Medicine in Rheumatoid Arthritis: A Clinician's Guide
      to the Future.
AB  - Personalized medicine refers to the utilization of technologies at the molecular
      level to understand disease processes and improve health outcomes. In rheumatoid
      arthritis (RA) some factors associated with disease outcome have been identified.
      These factors have not yet been integrated into a clinically useful tool to
      predict disease outcome in individual patients. Developments in pharmacogenomics
      are moving the field forward quite rapidly. Genetic variants, which may have a
      role in drug metabolism mediating either drug response or toxicity, have been
      identified for both traditional disease modifying antirheumatic drugs and
      biologic agents. Choosing a medication based on a patient's characteristics
      (sociodemographic, clinical, genetic) will result in better utilization of
      resources and better clinical outcomes. The ethical, political, and legal
      implications of personalized medicine need to be considered as well.

PMID- 22870433
TI  - Zoledronic Acid for the treatment and prevention of primary and secondary
      osteoporosis.
AB  - There is increasing interest in therapies that can be administered less
      frequently and/or avoid gastrointestinal irritation. The efficacy of once-yearly
      zoledronic acid (5 mg) in the treatment and prevention of osteoporosis has been
      evaluated in different patient populations. In the 3-year HORIZON-Pivotal
      Fracture Trial in postmenopausal women with osteoporosis, zoledronic acid reduced
      the risk of vertebral and hip fracture by 70% and 41%, respectively, versus
      placebo. The efficacy of zoledronic acid in preventing subsequent fracture in
      patients with a hip fracture was evaluated in the HORIZON-Recurrent Fracture
      Trial. New vertebral and nonvertebral fractures were significantly reduced by
      treatment initiated within 90 days of incident hip fracture, without evidence of
      delayed fracture healing. Data from a 1-year study show that a single zoledronic
      acid 5-mg infusion is superior to oral risedronate 5 mg/day for treatment and
      prevention of glucocorticoid-induced osteoporosis. Increases in bone mineral
      density and decreases in bone turnover markers were significantly greater with
      zoledronic acid than with risedronate. Two different treatment regimens of
      zoledronic acid were found to be more effective than placebo for prevention of
      bone loss in postmenopausal women and reducing markers of bone turnover after 2
      years.In conclusion, zoledronic acid 5 mg once-yearly infusion has demonstrated
      marked efficacy in the treatment and prevention of primary and secondary
      osteoporosis, with a combination of fracture risk reduction and prevention of
      bone loss at key sites. It is the only agent shown to reduce the incidence of
      fracture and mortality in patients with a previous low-trauma hip fracture.

PMID- 22870432
TI  - Paget's Disease of Bone: A Review of Epidemiology, Pathophysiology and
      Management.
AB  - Paget's disease of bone is a common disorder which may affect one or many bones.
      Although many patients are asymptomatic, a variety of symptoms and complications
      may occur. Fortunately, effective pharmacologic therapy, primarily with potent
      bisphosphonates, is now available to treat patients with complications or
      symptoms. This review of Paget's disease of bone will include epidemiology and
      pathophysiology, complications and clinical findings, indications for treatment,
      and the drugs currently available to treat this condition.

PMID- 22870434
TI  - Current evidence for osteoarthritis treatments.
AB  - Osteoarthritis (OA) is the most common form of arthritis and the leading cause of
      chronic disability among older people. The burden of the disease is expected to
      rise with an aging population and the increasing prevalence of obesity. Despite
      this, there is as yet no cure for OA. However, in recent years, a number of
      potential therapeutic advances have been made, in part due to improved
      understanding of the underlying pathophysiology. This review provides the current
      evidence for symptomatic management of OA including nonpharmacological,
      pharmacological and surgical approaches. The current state of evidence for
      disease-modifying therapy in OA is also reviewed.

PMID- 22870435
TI  - Bisphosphonates in the management of idiopathic hypercalciuria associated with
      osteoporosis: a new trick from an old drug.
AB  - Idiopathic hypercalciuria (IHC) is defined as a 24-hour urinary calcium excretion
      that exceeds 4 mg/kg/day, regardless of gender and in absence of systemic
      diseases or pharmacological treatments that may cause normocalcemic
      hypercalciuria (eg sarcoidosis, normocalcemic primary hyperparathyroidism,
      vitamin D intoxication, hyperthyroidism). Patients with IHC and nephrolithiasis
      often present increased bone turnover, decreased bone mineral density (BMD) and
      increased susceptibility to fragility fractures. Although the pathogenesis of IHC
      seems complex and multifactorial, recent evidences suggest that cells involved in
      bone resorption may play a critical role in the chain of events leading to the
      excessive urinary calcium excretion. Therefore, it has been proposed that
      bisphosphonates, potent inhibitors of bone resorption, may have beneficial
      effects in hypercalciuric patients with low BMD. This manuscript reports recent
      findings regarding the role of bone tissue in the pathogenesis of IHC, and
      supports the use of bisphosphonates in such conditions. It also reviews the
      literature on the effects of bisphosphonates in subjects with osteoporosis
      associated IHC.

PMID- 22870436
TI  - Anti-TNF Therapy in Ankylosing Spondylitis: Insights for the Clinician.
AB  - The introduction of tumour necrosis factor (TNF)-blocking therapy has
      revolutionized the management of ankylosing spondylitis (AS) over the last
      decade. This review highlights the current evidence relating to the use of TNF
      blocking therapy in AS. International guidelines for the use of TNF blockers in
      AS are summarized. An outline of the evidence for efficacy and safety of these
      drugs is included, highlighting recent data from registries and real-life
      observational studies. Such cohort data is also reviewed highlighting the
      evidence for 'switching' TNF blockers in AS in the case of non-response or
      adverse events. The potential new application of TNF blockers in preradiographic
      axial spondyloarthropathy (SpA) or 'early AS' is discussed with reviews of two
      recent studies in this area. Finally research into the possible additional
      impacts of TNF therapies is reviewed. The question of whether TNF blockers are
      truly disease modifying in AS remains unanswered with conflicting reports. The
      additional burden of AS in terms of cardiovascular disease is now becoming
      understood. Recent data from basic science studies highlights the potential
      impact of TNF blockers on this excess cardiovascular morbidity and mortality.
      Future studies and registry data will be able to assess whether TNF blockers have
      an additional role in controlling systemic inflammation and its associated
      cardiovascular risk.

PMID- 22870437
TI  - Treating reactive arthritis: insights for the clinician.
AB  - THERE ARE TWO MAIN FORMS OF REACTIVE ARTHRITIS (REA): postvenereal and
      postdysentery. Chlamydia trachomatis (Ct) is the major causative organism of the
      postvenereal type; Salmonella, Shigella, Campylobacter, and Yersinia are the
      major triggers for the postenteric type. All of these causative organisms have
      been shown to traffic to the synovium in affected individuals. However, one
      important difference is that the chlamydial organisms have been shown to be
      viable, whereas, in general, the postenteric organisms are not. Although
      estimates vary widely, it is felt that 30-50% of all cases of ReA become chronic
      and the remainder resolve spontaneously within weeks to months. These important
      differences need to be considered when reviewing the available therapeutic
      outcomes data. There is a relative paucity of prospective clinical trial data
      assessing various treatment strategies. A large breadth of clinical experience
      demonstrates that nonsteroidal anti-inflammatory drugs (NSAIDs) and
      corticosteroids are efficacious, but there have only been two rather small trials
      assessing NSAIDs and none with corticosteroids. Disease modifying drugs are
      sometimes utilized in more severe or chronic cases, but only sulfasalazine (SSZ)
      has been studied. Anti-tumor necrosis factor (TNF) therapy has proved remarkably
      efficacious with other types of spondyloarthritides, but there is very little
      data to support their use in ReA; theoretical concerns also exist with this drug
      class in ReA, specifically. Finally, antibiotics have been studied in several
      trials. A thorough analysis of these trials reveals equivocal results with a
      possible particular benefit in postchlamydial ReA. These data are reviewed with
      an emphasis on postchlamydial and postenteric ReA.

PMID- 22870438
TI  - Can Hip Fracture Prediction in Women be Estimated beyond Bone Mineral Density
      Measurement Alone?
AB  - The etiology of hip fractures is multifactorial and includes bone and fall
      related factors. Low bone mineral density (BMD) and BMD-related and BMD
      independent geometric components of bone strength, evaluated by hip strength
      analysis (HSA) and finite element analysis analyses on dual-energy X-ray
      absorptiometry (DXA) images, and ultrasound parameters are related to the
      presence and incidence of hip fracture. In addition, clinical risk factors
      contribute to the risk of hip fractures, independent of BMD. They are included in
      the fracture risk assessment tool (FRAX) case finding algorithm to estimate in
      the individual patient the 10-year risk of hip fracture, with and without BMD.
      Fall risks are not included in FRAX, but are included in other case finding
      tools, such as the Garvan algorithm, to predict the 5- and 10-year hip fracture
      risk. Hormones, cytokines, growth factors, markers of bone resorption and genetic
      background have been related to hip fracture risk. Vitamin D deficiency is
      endemic worldwide and low serum levels of 25-hydroxyvitamin D [25(OH)D] predict
      hip fracture risk. In the context of hip fracture prevention calculation of
      absolute fracture risk using clinical risks, BMD, bone geometry and fall-related
      risks is feasible, but needs further refinement by integrating bone and fall
      related risk factors into a single case finding algorithm for clinical use.

PMID- 22870439
TI  - Using hand bone mass measurements to assess progression of rheumatoid arthritis.
AB  - In rheumatoid arthritis (RA) bone involvement presents as joint erosions in
      addition to generalized and periarticular osteoporosis. Joint erosions on
      radiographs of the hands and feet are considered to be the gold standard to
      evaluate progression of bone and joint damage in RA, even though erosions on
      radiographs are not used as a marker of early bone involvement. Periarticular
      bone loss seen on radiographs may be the first sign of bone involvement in RA.
      Over the last decade there has been an increased awareness of the importance of
      early aggressive treatment in RA, leading to a need for methods which can
      identify bone involvement in the early stages of RA. As inflammatory bone loss,
      especially at the hand, has been shown to occur early in RA, quantitative
      measures of hand bone loss have been proposed as an outcome measure for the
      detection of bone involvement. In this review article we present data supporting
      the hypothesis that both erosions and osteoporosis in RA occur as a result of the
      same pathophysiological mechanisms activating the osteoclast. Furthermore the
      role of hand bone loss as an early marker of inflammatory bone involvement, a
      predictor of subsequent radiographic joint damage and a response variable to anti
      inflammatory treatment is discussed.

PMID- 22870440
TI  - The efficacy and safety of abatacept in rheumatoid arthritis.
AB  - Despite important progress in the treatment of rheumatoid arthritis in the last
      decade, even in the era of tumour necrosis factor (TNF) blockade there is a need
      for additional therapeutic options in many patients. In recent years three
      therapies with a distinct mode of action became available: rituximab, an anti-B
      cell therapy, tocilizumab, an anti IL-6 therapy, and abatacept, a costimulation
      blocker. Primary efficacy results of all three therapies are comparable at 6
      months, nevertheless they have distinct efficacy and safety profiles. In the
      current review we focus on specific aspects of efficacy and safety of abatacept:
      increasing clinical and X-ray improvements over time, important and stable
      responses over several years, timing of response, improvements in patient
      centered outcomes, and also long-term safety and easy administration with low
      rates of perfusion reactions. Currently, head to head comparisons between
      biologics are still lacking and registry data of drugs with a mode of action
      different to TNF blockade are still rare. In the meantime detailed analysis of
      all trials with a drug such as abatacept provides important information for the
      practicing rheumatologist.

PMID- 22870441
TI  - Effects of diacerein at the molecular level in the osteoarthritis disease
      process.
AB  - In osteoarthritis (OA), the alterations in joint tissues are numerous and involve
      morphological, biochemical and metabolic changes and an upregulation of the
      inflammatory pathways. The focus of this article is a brief narrative review of
      the effects of diacerein, an antirheumatic drug from the anthraquinone chemical
      class, and its active metabolite, rhein, on the factors that participate in the
      complex interaction between OA tissues and cells leading to the progression of
      joint structural changes.

PMID- 22870442
TI  - Viscosupplementation with hylan g-f 20 in patients with osteoarthrosis of the
      knee.
AB  - Viscosupplementation (VIS) is one of several treatment modalities for
      osteoarthritis of the knee. It is useful in the treatment of osteoarthritis when
      other methods of conservative care have failed and it may be a safer method of
      treatment than oral chemical therapy which can have significant side effects with
      even short-term usage. The biochemical effects of hyaluronic acid are
      incompletely understood, however there are several accepted modes of action which
      result in a positive clinical effect on the function of the knee joint. There is
      some evidence that hyaluronic acid preparations with a higher molecular weight
      may be more beneficial to the patient. It is commonly used after arthroscopic
      meniscectomy and or debridement of the knee in a patient with chondral disease.
      The clinical effects have been well documented in multiple studies in patients
      with mild to moderate osteoarthritis in study groups before or after arthroscopic
      surgery of the knee. Adverse events do occur and are easily treated with only
      rare case reports of systemic effects. Furthermore, there is some evidence that
      VIS can prolong the need for total knee arthroplasty in the older patient as
      well.

PMID- 22870443
TI  - Strontium Ranelate: Long-Term Efficacy against Vertebral, Nonvertebral and Hip
      Fractures in Patients with Postmenopausal Osteoporosis.
AB  - Osteoporosis treatments need to combine an unequivocally demonstrated reduction
      of fractures, at various skeletal sites, long-term safety, and a user-friendly
      profile, optimizing therapeutic adherence. Strontium ranelate is the first
      compound to simultaneously decrease bone resorption and stimulate bone formation.
      Its antifracture efficacy, at various skeletal sites, has been established up to
      8 years, through studies of the highest methodological standards. Increases in
      bone mineral density, observed after 1 year of treatment, are predictive of the
      long-term fracture efficacy, hence suggesting, for the first time in
      osteoporosis, that bone densitometry can be used as a monitoring tool for both
      efficacy and compliance. Owing to a positive benefit/risk ratio, strontium
      ranelate may now be considered as a first-line treatment in the management of
      osteoporosis.

PMID- 22870444
TI  - Risk factors for coronary heart disease in connective tissue diseases.
AB  - Atherosclerosis and cardiovascular disease risk is enhanced in certain connective
      tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis
      (RA), systemic vasculitis and antiphospholipid syndrome. The reason for this
      accelerated process is likely to be multifactorial. Traditional risk factors are
      more prevalent in some of these patient groups compared with the general
      population (e.g. smoking in RA and hypertension in SLE). However, these factors
      do not fully explain that enhanced risk. Chronic inflammation associated with
      these disorders as well as some specific autoantibodies have been shown to
      contribute to this increased risk although their role remains controversial. The
      role of therapies is unclear and while steroids may exacerbate metabolic risk
      factors, the anti-inflammatory effects of traditional and more novel biological
      therapies may reduce overall cardiovascular risk in these populations. We
      recommend proactive screening for modifiable cardiovascular risk factors in
      patients with these conditions.

PMID- 22870445
TI  - Treating Sjogren's Syndrome: Insights for the Clinician.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease that affects the
      exocrine glands, mainly the salivary and lachrymal glands, with consequent
      persistent dryness of the mouth and eyes. In addition to the clinical
      manifestations related to the exocrine gland involvement, a consistent prevalence
      of patients may present systemic manifestations. Some of these can be ascribed to
      the periepithelial extension of lymphocytic infiltration whilst others are
      determined by an immunomediated process affecting small- or medium-size vessels.
      While the use of tear and saliva substitutes and local or systemic stimulation of
      residual secretions represent the mainstays of the therapy of sicca component,
      different immunomodulating or immunosuppressive agents are usually required to
      treat extraglandular features, similarly to what happens in other connective
      tissue diseases. In the last few years, the advancement in the understanding the
      pathogenetic mechanisms of this disorder and the availability of new biologic
      target therapies seem to offer completely new therapeutic options. The use of B
      cell depleting or modulating therapies has achieved promising results.

PMID- 22870446
TI  - Bone density, balance and quality of life of postmenopausal women taking
      alendronate participating in different physical activity programs.
AB  - BACKGROUND: The objective of this study was to determine the effects of different
      physical activity (PA) programs on bone density, balance and quality of Life of
      postmenopausaL women taking concomitant aLendronate. A quasi-experimental study
      was conducted with 35 volunteers divided into four groups: practitioners of
      resistance training (RTG, n = 9, 49.8+/-4.2 years), judo (JUG, n= 11, 52.2 +/-5.3
      years), water aerobics (WAG, n = 8, 57.1 +/-7.4 years) and the control group (CG,
      n = 7, 53.8+/-4.4 years). METHODS: The following assessment tools were used: bone
      mineral density (BMD) measured by dual X-ray absorptiometry of the spine and
      proximal femur, the 'Osteoporosis Assessment Questionnaire' (OPAQ) and the
      'Static Balance Test with Visual Control'. The physical activities were planned
      for 12 months in cycles with different intensities. A two-way analysis of
      variance (ANOVA) was used for analysis between groups, and a Scheffe post-hoc
      test was used for multiple comparisons. RESULTS: The multiple comparisons results
      showed that the RTG and JUG groups were significantly more efficient in the
      variables studied, including: Lumbar BMD (Delta% = 6.8%, p = 0.001), balance
      (Delta% = 21.4%, p = 0.01), OPAQ (Delta% = 9.1%, p = 0.005) and Lumbar BMD
      (Delta% = 6.4%, p = 0.003), balance (Delta% = U%, p = 0.02) and OPAQ (Delta% =
      16.8%, p =0.000) compared with the CG. Furthermore, the RTG (Delta% = 4.8%, p
      =0.02) was significantly better than the WAG for the neck of femur BMD, and the
      JUG (Delta% = 16.8, p = 0.0003) also demonstrated superiority to the WAG in the
      OPAQ. CONCLUSIONS: The physical activities studied appear to improve BMD, balance
      and quality of Life of postmenopausaL women taking a bisphosphonate. In this
      small sample, the RTG and the JUG groups were superior to the other groups.

PMID- 22870447
TI  - The FIBRO System: A Rapid Strategy for Assessment and Management of Fibromyalgia
      Syndrome.
AB  - Fibromyalgia syndrome (FMS) is a complex disorder of widespread pain and
      tenderness associated with numerous other symptoms including fatigue, cognitive
      dysfunction, nonrestorative sleep, depression, anxiety, and stiffness. While new
      diagnostic criteria and previous management guidelines require quantitation of
      the severity of associated FMS symptoms experienced by individual patients, no
      system for rapid patient assessment has been made available to provide a basis
      for diagnosis, treatment selection and follow-up for clinicians in busy practices
      who have limited time. This review presents the FIBRO System, an easily
      remembered system for FMS symptom quantitation using the FIBRO mnemonic along
      with verbal questions on simple 0-10 scales to assess symptom severity (the FIBRO
      Problem Scale) and response to treatment (the FIBRO Change Scale) along with
      recommendations for pharmacologic and nonpharmacologic therapies to address
      individual FIBRO symptoms. This symptom-based approach can improve the care of
      FMS patients by providing a comprehensive, focused assessment in limited time.

PMID- 22870448
TI  - Milnacipran: a selective serotonin and norepinephrine dual reuptake inhibitor for
      the management of fibromyalgia.
AB  - Milnacipran, a serotonin and norepinephrfrine reuptake inhibitor with
      preferential inhibition of norepinephrine reuptake over serotonin, is approved in
      the United States for the management of fibromyalgia. Owing to its effects on
      norepinephrine and serotonin, as well as its lack of activity at other receptor
      systems, it was hypothesized that milnacipran would provide improvements in pain
      and other fibromyalgia symptoms without some of the unpleasant side effects
      associated with other medications historically used for treating fibromyalgia.
      The clinical safety and efficacy of milnacipran 100 and 200 mg/day in individuals
      with fibromyalgia has been investigated in four large, randomized, double-blind,
      placebo-controlled studies and three long-term extension studies. The clinical
      studies used composite responder analyses to identify the proportion of
      individual patients reporting simultaneous and clinically significant
      improvements in pain, global status, and physical function, in addition to
      assessing improvement in various symptom domains such as fatigue and
      dyscognition. In the clinical studies, patients receiving milnacipran reported
      significant improvements in pain and other symptoms for up to 15 months of
      treatment. Most adverse events were mild to moderate in severity and were related
      to the intrinsic pharmacologic properties of the drug. Long-term exposure to
      milnacipran did not result in any new safety concerns. As with other serotonin
      and norepinephrine reuptake inhibitors, increases in heart rate and blood
      pressure have been observed in some patients with milnacipran treatment.

PMID- 22870449
TI  - Management of antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is an autoimmune disorder presenting with
      tissue injury in various organs related to large- or small-vessel thrombosis
      associated with antiphospholipid and antiprotein/phospholipid complex antibodies.
      Although the pathophysiology, diagnosis, and clinical scenario may seem clear and
      straightforward, a more detailed examination reveals a more complex and uncertain
      picture related to the management of APS. This article reviews the current
      situation relating to APS therapy by evaluating the different clinical features
      of the syndrome ranging from thrombosis to pregnancy complications together with
      new strategies and pharmacological approaches.

PMID- 22870450
TI  - Treatment strategies for osteoarthritis patients with pain and hypertension.
AB  - Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant
      diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and
      cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP),
      which is more marked in patients with established hypertension. NSAIDs and COX-2
      inhibitors attenuate the antihypertensive effect of several antihypertensive
      agents. Frequent BP controls are needed in treated hypertensive patients who are
      concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase
      in BP may be associated with an important rise in the risk of major
      cardiovascular complications. In meta-analyses, an increase in systolic BP of
      5mmHg was associated with a 25% higher risk of cardiovascular events. These data
      have been confirmed in randomized studies with rofecoxib and celecoxib, where a
      modest increase in BP was associated with a significantly higher risk of
      cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric
      oxide donator (CINOD) class is promising in the treatment of patients with OA.
      Naproxcinod, the first CINOD investigated in clinical trials, is composed of the
      traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating
      moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide
      a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise
      in normotensive and hypertensive patients observed with naproxen. The BP benefit
      of naproxcinod over naproxen was greater in patients concomitantly receiving
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
      These investigational data suggest that naproxcinod is a valuable alternative to
      NSAIDs and COX-2 inhibitors for treatment of OA patients.

PMID- 22870451
TI  - The role of interleukin 6 in the pathophysiology of rheumatoid arthritis.
AB  - Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the
      pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the
      synovial fluid and serum of patients with RA and the level correlates with the
      disease activity and joint destruction. IL-6 can promote synovitis and joint
      destruction by stimulating neutrophil migration, osteoclast maturation and
      vascular endothelial growth factor (VEGF)-stimulated pannus proliferation. IL-6
      may also be mediating many of the systematic manifestations of RA including
      inducing the acute-phase reaction [including C-reactive protein (CRP)], anaemia
      through hecipidin production, fatigue via the hypothalamic-pituitary-adrenal
      (HPA) axis) and osteoporosis from its effect on osteoclasts. In addition, IL-6
      may contribute to the induction and maintenance of the autoimmune process through
      B-cell maturation and TH-17 differentiation. All of the above makes IL-6 blockade
      a desirable therapeutic option in the treatment of RA. Following successful
      animal studies, a humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal
      antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown
      to be an effective treatment in several large phase III clinical trials in RA
      with rapid and sustained improvement in disease activity, reducing radiographic
      joint damage and improving physical function.

PMID- 22870453
TI  - Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and
      inflammatory diseases.
AB  - Phosphodiesterase 4 (PDE4) is a key enzyme in the degradation of cyclic adenosine
      monophosphate and is centrally involved in the cytokine production of
      inflammatory cells, angiogenesis, and the functional properties of other cell
      types such as keratinocytes. In this review article, apremilast, a novel small
      molecule inhibitor of PDE4, is introduced. Apremilast has profound anti
      inflammatory properties in animal models of inflammatory disease, as well as
      human chronic inflammatory diseases such as psoriasis and psoriatic arthritis.
      Apremilast blocks the synthesis of several pro-inflammatory cytokines and
      chemokines, such as tumor necrosis factor alpha, interleukin 23, CXCL9, and
      CXCL10 in multiple cell types. In contrast to the biologics, which neutralize pro
      inflammatory mediators at the protein level, apremilast modulates production of
      these mediators at the level of mRNA expression. Apremilast also interferes with
      the production of leukotriene B4, inducible nitric oxide synthase, and matrix
      metalloproteinase and reduces complex inflammatory processes, such as dendritic
      cell infiltration, epidermal skin thickening, and joint destruction. As this
      novel PDE4 inhibitor interferes with several key processes of inflammation, it
      may emerge as a promising new drug for the treatment of chronic inflammatory
      diseases such as those of the skin and the joints.

PMID- 22870452
TI  - The role of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors (statins)
      in modern rheumatology.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase commonly
      known as statins are widely used for treating hypercholesterolemia. However,
      there is much evidence to suggest that statins may have other properties in
      addition to their cholesterol-lowering effect. In particular, statins may
      neutralize post-translational prenylation of vitally important regulatory small
      GTPases, which are involved in several processes such as tissue fibrosis, cell
      maturation, apoptosis, immune cell maturation, and immune response. The
      beneficial effect of statins has been reported in animal and in vitro models as
      well as in some clinical studies. As they have an acceptable safety profile,
      statins may be considered, in selected cases, as a valuable concomitant therapy
      in the treatment of rheumatic and autoimmune disorders.

PMID- 22870454
TI  - Managing Hip and Knee Osteoarthritis with Exercise: What is the Best
      Prescription?
AB  - Hip and knee osteoarthritis are common, chronic, and disabling. Therapeutic
      exercise is a component of all major rheumatologic society guidelines, yet the
      frequency, dose, duration, and therapeutic threshold for exercise are not clearly
      delineated. This review summarizes current studies of exercise for hip and knee
      osteoarthritis, discusses issues that influence the design, interpretation, and
      aggregation of results and how these factors impact the translation of data into
      clinical practice. A review of databases to identify current randomized
      controlled trials (2000 to present) of exercise to manage the symptoms of hip and
      knee osteoarthritis is discussed here. One study enrolling only hip patients was
      identified. Six studies of outcomes for individuals with hip or knee
      osteoarthritis and 11 studies of persons with knee osteoarthritis were found.
      Limited studies focus specifically on exercise for persons with hip
      osteoarthritis. Exercise is provided as a complex intervention combining multiple
      modes and provided in various settings under a range of conditions. Regardless of
      the variability in results and inherent biases in trials, exercise appears to
      reduce pain and improve function for persons with knee osteoarthritis and provide
      pain relief for persons with hip osteoarthritis. Given the complexity of exercise
      interventions and the specific issues related to study design, novel approaches
      to the evaluation of exercise are warranted.

PMID- 22870455
TI  - Opioids in chronic musculoskeletal conditions.
AB  - The use of opioids for benign disorders has been limited by concerns about these
      compounds' potential adverse events and their possible misuse. However, during
      the last few years an increased use in nonmalignant disorders, including
      rheumatologic diseases, has been observed. Herein, we review the scientific
      evidence for opioid therapy in three common scenarios in clinical rheumatology.
      Low back pain is a very frequent reason for consultation. Overall, the large
      majority of studies show a positive, yet rather moderate, effect of opioids in
      pain control, as well as in other outcomes including mood, work disability and
      anxiety. Similarly, opioids seem to have a role in the management of hip and knee
      osteoarthritis; indeed, they have been included in all international guidelines
      for the treatment of these conditions. However, clinical studies addressing
      opioid use in clinical situations are plagued by methodological limitations;
      furthermore, the large majority of these studies only provide short-term
      information about opiod utilization in these patients. Finally, opioids are
      currently being used as complementary therapy in inflammatory joint conditions
      whereby they may significantly improve the quality of life of some of these
      patients. Regarding their safety, severe adverse events, including abnormal drug
      seeking behaviour, are very rare, but mild adverse events are frequent leading to
      drug discontinuation in a significant number of cases.

PMID- 22870456
TI  - Is there a place for nonbiological drugs in the treatment of rheumatoid
      arthritis?

PMID- 22870457
TI  - The Relationship between Meniscal Tears and Meniscal Position.
AB  - OBJECTIVE: To investigate how different types of meniscal tears predispose to
      different patterns of meniscal position in subjects with and without symptomatic
      knee osteoarthritis (OA). METHODS: A cross-sectional analysis of 161 women
      participating in an observational study to evaluate knee OA progression was
      performed using baseline MRI data. Meniscal morphologic features were scored in
      three separate locations. Meniscal position measures were determined for
      extrusion and proportion of coverage. Analysis was performed using multiple
      linear regression models treating each tear type as an individual variable with a
      binary response. RESULTS: Complex tears, cysts and maceration of the medial
      meniscus were associated with more medial (p=0.0004, p=0.004, p <0.0001,
      respectively) and anterior extrusion (p =0.03, p=0.03, p<0.0001, respectively)
      than normal menisci. Horizontal tears of the lateral meniscus had more lateral
      (p=0.005) and anterior extrusion (p<0.0001) than normal menisci. Anterior and
      body tears of the medial meniscus were associated with more anterior extrusion
      (p=0.0006, p=0.01, respectively), whereas meniscal body tears alone had more
      medial extrusion than normal menisci (p= 0.0002). Meniscal body tears of the
      lateral meniscus had more lateral extrusion than normal menisci (p=0.01).
      CONCLUSION: Anterior horn and meniscal body tears and the more severe macerated
      and complex tear types predisposed to more medial meniscal extrusion. Laterally,
      only meniscal body and horizontal tears significantly affected extrusion,
      potentially reflecting a lower overall prevalence of lateral meniscal tears.
      These results may have important implications in identifying tear types
      associated with more meniscal dysfunction, with the ultimate goal of identifying
      those at greatest risk for knee OA progression.

PMID- 22870458
TI  - Current Aspects of Pathogenesis in Sjogren's Syndrome.
AB  - Sjogren's syndrome is a chronic autoimmune process that primarily affects the
      exocrine glands and leads to their functional impairment. The exocrine gland
      involvement is characterized by a focal, mononuclear cell infiltrate which is
      accumulated around ducts and, in some patients, extends and replaces the
      secretory functional units. The mechanisms of this autoimmune 'exocrinopathy' are
      not fully understood. The immune attack that follows activation or apoptosis of
      glandular epithelial cells exposing autoantigens in genetically predisposed
      individuals may drive the immune-mediated tissue injury. Abnormalities related to
      the upregulation of type I interferon-regulated genes (interferon signature),
      abnormal expression of B-cell-activating factor (BAFF) and activation of the IL
      23/TH17 pathway are among the immune mediators implicated in the pathogenesis of
      autoimmune lesions within the salivary glands. Such abnormalities demonstrate the
      complex interplay between innate and adaptive immunity that contributes to
      autoimmune 'exocrinopathy'.

PMID- 22870459
TI  - Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to
      clinical recommendations.
AB  - Chondroitin sulfate (CS) is recommended as a therapeutic intervention in the
      multimodal approach of osteoarthritis (OA) management. CS has been studied
      extensively to describe its pharmacology (pharmacokinetic, in vitro and in vivo
      effects) and its clinical efficacy. Various results have been reported depending
      on the system of evaluation (model, dosage and duration) and the source of CS
      (origin and quality). The purpose of this review was to gather most of the
      available information about CS and to discuss its potency in OA management.

PMID- 22870460
TI  - The role of synovitis in osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis worldwide yet there is
      still a lack of effective treatments for this condition. Increasingly, attention
      has turned to the role of the synovium in OA as it is now recognized, in part
      from the use of modern imaging techniques, that synovitis is both common and
      associated with pain. This offers a target for treatment, for both symptom and
      potential structure modification. In this review we discuss the evidence for
      histological and imaging-detected synovitis and the current role of antisynovial
      therapies in OA.

PMID- 22870461
TI  - Is remission a more realistic goal in psoriatic arthritis?

PMID- 22870462
TI  - Physical functioning measures and risk of falling in older people living in
      residential aged care facilities.
AB  - BACKGROUND: Frail older individuals living in residential aged care facilities
      (RACFs) have impaired physical function compared with to older people living in
      the community. In residents of RACFs, we aimed to produce sex-specific means and
      empirical norms of objective physical function measures to ascertain whether
      these measures are predictors of falls. METHODS: Data were extracted from a large
      cohort study investigating fall and fracture rates in RACFs in the Northern
      Sydney Health Area, Australia. RESULTS: Study participants (n = 602, 70.9%
      female) were recruited from 51 RACFs. Cohort means (+/-standard deviation) for
      females were for grip strength (GS) 16.8+/-5.3 kg, simple reaction time (RT)
      384+/-154 ms, walking speed (WS) 0.56 +/-0.20 ms(-1), balance category (B) 3.8+/
      1.1 and sit to stand category (STS) 3.6+/-0.5. For males, means were for GS
      28.8+/-7.8 kg, RT 335+/-150 ms, WS 0.62+/-0.22 ms(-1), B 4.1+/-1.1 and STS 3.7+/
      0.5. Means of B and STS decreased significantly over the 1-year study period for
      males and females (p < 0.001). Individual multivariate negative binomial
      regression models for each functional outcome showed having a WS <0.6 ms(-1) (IRR
      = 1.37, 95% Cl = 1.03-1.84), a STS score of 3 (IRR = 1.39, 95% Cl = 1.09-1.79)
      and B category of 3 or 5 (IRR = 1.69, 95% CI = 1.29-2.22) were significantly
      associated with an increased fall rate. CONCLUSIONS: This study establishes
      normative values for physical function tests in mobile residents of RACFs and
      demonstrates that walking speed, balance and sit to stand impairments are
      associated with falls in this group.

PMID- 22870463
TI  - Medical treatment of osteoporotic vertebral fractures.
AB  - A vertebral fracture is a serious symptom of osteoporosis. Vertebral fractures
      cause moderate-to-severe back pain for a shorter or longer duration, increase the
      risk of a subsequent vertebral fracture approximately four-fold, reduce quality
      of life significantly and are associated with increased mortality. In order to
      choose the optimal treatment for the patient, the severity and type of
      osteoporosis should be investigated. Prevention of new osteoporotic fractures can
      be accomplished through treatment with both antiresorptive and anabolic
      treatments. The antiresorptive treatment modalities comprise calcium, vitamin D,
      bisphosphonates, hormone therapy, selective oestrogen receptor modulators
      (SERMs), strontium ranelate, receptor activator of NF-kB ligand (RANKL) antibody
      and calcitonin. The anabolic treatments comprise teriparatide and parathyroid
      hormone [(PTH)-(1-84)]. Adherence with treatment of osteoporosis is generally
      poor and therefore once the choice of treatment has been made and the patient has
      been instructed properly, long-term adherence to the treatment should be secured
      through information and regular control visits.

PMID- 22870464
TI  - Cutaneous side effects of antiosteoporosis treatments.
AB  - Cutaneous adverse reactions are reported for many therapeutic agents and, in
      general, are observed in between 0% and 8% of treated patients depending on the
      drug. Antiosteoporotic agents are considered to be safe in terms of cutaneous
      effects, however there have been a number of case reports of cutaneous adverse
      reactions which warrant consideration. This was the subject of a working group
      meeting of the European Society for Clinical and Economic Aspects of Osteoporosis
      and Osteoarthritis in April 2009, which focused on the impact of cutaneous
      adverse reactions and drug-induced hypersensitivity in the management of
      postmenopausal osteoporosis. This position paper was drafted following these
      discussions and includes a flowchart for their recognition. Cutaneous adverse
      reactions observed with antiosteoporotic agents were reviewed and included
      information from case reports, regulatory documents and pharmacovigilance. These
      reactions ranged from benign effects including exanthematous or maculopapular
      eruption (drug rash), photosensitivity and urticaria, to the severe and
      potentially life-threatening reactions of angioedema, drug rash with eosinophilia
      and systemic symptoms (DRESS), Stevens Johnson syndrome and toxic epidermal
      necrolysis. A review of the available evidence demonstrates that cutaneous
      adverse reactions occur with all commonly used antiosteoporotic treatments.
      Notably, there are reports of Stevens Johnson syndrome and toxic epidermal
      necrolysis for bisphosphonates, and of DRESS and toxic epidermal necrolysis for
      strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases).
      In general, with proper management and early recognition, including immediate and
      permanent withdrawal of the culprit agent, accompanied by hospitalization,
      rehydration and systemic corticosteroids if necessary, the prognosis is positive.

PMID- 22870465
TI  - Recent advances in imaging in psoriatic arthritis.
AB  - The recent introduction of effective therapies in psoriatic arthritis (PsA) has
      increased the demand for efficient tools for diagnosis, monitoring and
      prognostication of PsA, and has caused an increased research effort within
      imaging in this disease. The clinical appearance of PsA is very diverse,
      involving the spine, sacroiliac joints, peripheral joints and/or entheses, and
      accordingly imaging findings vary. In the present paper, we present a review of
      the recent advances in imaging in PsA, focusing primarily on ultrasonography and
      magnetic resonance imaging of peripheral disease manifestations.

PMID- 22870466
TI  - Malignancy risk in vasculitis.
AB  - The vasculitides encompass a rare subset of autoimmune diseases. Reports of the
      concurrent association of malignancies with some forms of vasculitis raise the
      possibility that patients with certain types of vasculitis may be at increased
      risk of cancer. Conversely, some forms of vasculitis may be a manifestation of
      malignancy. We review cancer risk in patients with large vessel vasculitis (giant
      cell arteritis and Takayasu arteritis), polyarteritis nodosa, and the circulating
      antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. In addition
      we discuss vasculitis as a paraneoplastic phenomenon, highlighting polyarteritis
      nodosa in association with hairy cell leukemia and reviewing the most common
      vasculitic manifestation of cancer, cutaneous vasculitis.

PMID- 22870467
TI  - Evidence of sustained vertebral and nonvertebral antifracture efficacy with
      ibandronate therapy: a systematic review.
AB  - BACKGROUND: The antifracture efficacy of ibandronate at vertebral and
      nonvertebral sites was assessed. METHODS: A literature review of randomized phase
      III clinical trials, meta-analyses or observational studies that reported
      fracture endpoints or surrogate markers, and compared ibandronate with placebo or
      an active comparator. RESULTS: In a phase III study, 2.5 mg daily oral
      ibandronate reduced the incidence of new vertebral fractures versus placebo and
      the relative risk reduction (RRR) was sustained over 3 years (62%; p = 0.0001).
      In two bridging studies, oral ibandronate 150 mg once monthly and 3 mg quarterly
      intravenous (i.v.) were superior to oral 2.5 mg daily in producing bone mineral
      density (BMD) increases at all sites over 2 years (p < 0.05). These improvements
      were sustained over 5 years. In meta-analyses of pivotal ibandronate studies,
      doses equivalent to annual cumulative exposure (ACE) >= 10.8 mg (including 150 mg
      once monthly and 3 mg quarterly i.v.) significantly reduced the incidence of
      nonvertebral fractures versus placebo or ACE 5.5 mg (2.5 mg daily) (RRR 29.9% and
      38%, respectively; p < 0.05). Therefore, prevention of nonvertebral fractures was
      found in all patients with the commercially available highest doses, and not only
      in high-risk patients as observed in randomized clinical trials with lower doses.
      Finally, a 12-month, observational study of claims databases reported comparable
      rates of nonvertebral fractures and a statistically significantly lower rate of
      vertebral fractures (p < 0.01) with ibandronate versus weekly bisphosphonates.
      CONCLUSION: A large body of evidence suggests that ibandronate has sustained
      vertebral and nonvertebral antifracture efficacy in women with postmenopausal
      osteoporosis.

PMID- 22870468
TI  - Factors that contribute to low bone density in postmenopausal women in different
      amazonian communities.
AB  - BACKGROUND: The aim of this study was to verify socioeconomic differences,
      nutrition, body balance and quality of life (QoL) in postmenopausal women with
      low bone mineral density (BMD) in two Amazonian communities. METHODS: A total of
      42 female volunteers participated in the study. The volunteers were separated
      into two groups: Villa (n = 20; 53 +/- 5.5 years) and City (n = 22; 56 +/- 7.9
      years). The following evaluation instruments were used: dual energy X-ray
      absorptiometry (DXA); a socioeconomic questionnaire; a QoL questionnaire; a
      dietary habits questionnaire; and a balance test. Parametric and nonparametric
      tests were used. RESULTS: The data showed significant differences in
      socioeconomic level (Delta%=+15.9%, p = 0.000), lumbar spine L(2)-L(4) (Delta% =
      +0.10%, p = 0.007), balance (Delta% = +4.3%, p = 0.03) and some important aspects
      of nutrition, such as the consumption of milk (Delta%=+34%, p = 0.01) and alcohol
      (+14.8%, p = 0.0001). These significant differences also contributed to the total
      QoL score (Delta%=+76.2%, p = 0.000) and the majority of the QoL-related
      functions. CONCLUSION: This study verified that socioeconomic level, nutritional
      status, physical activity levels and QoL can influence the BMD of postmenopausal
      women. The study suggests new strategies for official health organizations to use
      in order to prevent and treat osteoporosis. In addition, this study can provide
      an orientation to physical activity, nutrition and medical professionals.

PMID- 22870469
TI  - An overview of the management of persistent musculoskeletal pain.
AB  - Musculoskeletal pain is a common reason for patients to seek care from healthcare
      providers. These conditions are predominantly nontraumatic injuries with a broad
      differential diagnosis and often without a specific diagnosis despite thorough
      history and examination. The management of these conditions is often discouraging
      for patients with continued chronic symptoms despite numerous diagnostic workups
      and treatment options. Effective communication with respect to the patient's
      goals is the key to a good outcome. The combination of an accurate diagnosis, an
      informed, motivated patient and a comprehensive review of the potential treatment
      options is beneficial for long-term success.

PMID- 22870470
TI  - Sternocostoclavicular hyperostosis: a review.
AB  - Sternocostoclavicular hyperostosis (SCCH) is a chronic inflammatory disorder
      which presents with erythema, swelling, and pain of the sternoclavicular joint.
      Approximately one half of patients have acne or pustular lesions with the best
      described association being with palmoplantar pustulosis (PPP). Extrasternal
      articular disease occurs in about a quarter of patients. The inflammatory process
      spans several years and has periods of exacerbation followed by remission. The
      histologic picture demonstrates a sterile osteomyelitis of the sternum and medial
      end of the clavicle. The diagnosis of SCCH is confirmed radiographically by
      hyperostosis and sclerosis of the sternum with involvement of the first rib on
      computed tomography (CT). The focal uptake of radiopharmaceutical on bone
      scintigraphy called the 'bullhead' sign is highly sensitive of SCCH. Treatment is
      aimed at easing pain and modifying the inflammatory process. Evidence over the
      last two decades suggests a role for intravenous bisphosphonates and tumor
      necrosis factor alpha inhibitors. A low level of awareness of SCCH often leads to
      a delay in diagnosis. This translates into significant morbidity and brings a
      psychological burden. Untreated chronic inflammation of the sternoclavicular
      joint leads to restricted mobility and secondary degenerative joint changes. In
      the search for a diagnosis, patients often undergo multiple serologic and imaging
      studies and in the experience of the author are referred to multiple specialists
      before a correct diagnosis is made. Greater awareness of SCCH is needed to
      prevent the irreversible physical and psychological impairments associated with
      the disease.

PMID- 22870471
TI  - Hyperbaric oxygen effects on sports injuries.
AB  - In the last decade, competitive sports have taken on a whole new meaning, where
      intensity has increased together with the incidence of injuries to the athletes.
      Therefore, there is a strong need to develop better and faster treatments that
      allow the injured athlete to return to competition faster than with the normal
      course of rehabilitation, with a low risk of re-injury. Hyperbaric therapies are
      methods used to treat diseases or injuries using pressures higher than local
      atmospheric pressure inside a hyperbaric chamber. Within hyperbaric therapies,
      hyperbaric oxygen therapy (HBO) is the administration of pure oxygen (100%) at
      pressures greater than atmospheric pressure, i.e. more than 1 atmosphere absolute
      (ATA), for therapeutic reasons. The application of HBO for the treatment of
      sports injuries has recently been suggested in the scientific literature as a
      modality of therapy either as a primary or an adjunct treatment. Although results
      have proven to be promising in terms of using HBO as a treatment modality in
      sports-related injuries, these studies have been limited due to the small sample
      size, lack of blinding and randomization problems. HBO seems to be promising in
      the recovery of injuries for high-performance athletes; however, there is a need
      for larger samples, randomized, controlled, double-blinded clinical trials
      combined with studies using animal models so that its effects and mechanisms can
      be identified to confirm that it is a safe and effective therapy for the
      treatment of sports injuries.

PMID- 22870472
TI  - Stem cell therapy: resetting autoimmunity or postponing the inevitable?

PMID- 22870473
TI  - Tocilizumab: a novel humanized anti-interleukin 6 receptor antibody for the
      treatment of patients with rheumatoid arthritis.
AB  - Tocilizumab (TCZ; RoActemra(r) or Actemra(r)) is a recombinant humanized
      monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist. For
      rheumatoid arthritis (RA), intravenous (IV) TCZ 8 mg/kg every 4 weeks has been
      approved since 2008 in Japan (where it is also approved for polyarticular
      juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis and
      Castleman's disease), and since 2009 in Europe in combination with methotrexate
      (MTX) for the treatment of moderate to severe active RA in adult patients with
      inadequate response to, or intolerance of, disease-modifying antirheumatic drug
      (DMARD) or tumor necrosis factor (TNF) antagonist therapy. It may also be
      administered as monotherapy in the same dose regimen in patients with
      methotrexate intolerance or with inadequate response to MTX. Since January 2011
      in the United States, the indication for treatment with TCZ for RA patients with
      an inadequate response to one or more TNF antagonists was extended to patients
      with moderately to severely active RA, and the recommended starting dose is 4
      mg/kg every 4 weeks, with an increase to 8 mg/kg based on clinical response. All
      of these approvals are based on the effectiveness and safety of the 8 mg/kg dose
      regimen when administered either as monotherapy or in combination with
      conventional DMARDs in well-designed clinical studies in adult patients with
      moderate to severe RA. TCZ at this dose is more effective than placebo, MTX or
      other DMARDs in reducing disease activity and improving health-related quality of
      life (HR-QoL). Although there were fewer responses with the 4 mg/kg dose, this
      dose every 4 weeks was not statistically different to 8 mg/kg when administered
      in combination with MTX, and this dose is the recommended starting dose in the
      US. Both doses have also been shown to inhibit structural joint damage in
      patients with an inadequate response to MTX. Thus, TCZ is an important new
      treatment option in patients with moderate to severe RA.

PMID- 22870474
TI  - Methotrexate: optimizing the efficacy in rheumatoid arthritis.
AB  - Methotrexate (MTX) is currently the most frequently used drugs in the treatment
      of rheumatoid arthritis (RA). The drug had been synthesized in 1948 and first
      tests to treat patients with psoriasis and RA were published in 1951. However,
      until the 1980s there was only limited use of MTX in the treatment of RA. Since
      the 1990s MTX is the disease-modifying antirheumatic drug (DMARD) of first choice
      for the treatment of RA in most countries worldwide. By definition, DMARDs in RA
      are those compounds for which an inhibiting effect on radiographic progression
      has been demonstrated. Several combinations of DMARDs have been tested, most
      commonly with MTX as the anchor drug. Regarding the route of administration of
      MTX there is some evidence that the parenteral route, most often performed
      subcutaneously, has some additional benefits over the oral route. In MTX
      monotherapy, dosages up to 30 mg/week are now used. There are now three main
      combinations that are playing an important role: MTX + sulfasalazine (SSZ) +
      hydroxychloroquine, MTX + leflunomide (LEF), and MTX + biologics such as
      antitumour necrosis factor (anti-TNF) and other new compounds which block the
      interleukin 6 (IL6) receptor or T-cell activation and delete B cells. Regarding
      clinical efficacy, MTX monotherapy has performed almost similarly well in
      comparison with biologic mono-therapy, both usually combined with
      glucocorticoids. However, structural damage is usually inhibited to a
      significantly greater degree with the biologics. The combination of MTX with
      biologics has proven superior to either agent alone in all aspects. Current
      strategic regimens which concentrate on systematic ways to bring patients into
      remission all include MTX as first choice.

PMID- 22870475
TI  - Efficacy and safety data of belimumab in patients with systemic lupus
      erythematosus.
AB  - Belimumab is a human genome derived monoclonal antibody with specificity for BLyS
      (B lymphocyte stimulator, or B-cell activating factor [BAFF]), a cytokine that
      promotes the survival and maturation of B cells into antibody-secreting
      plasmablasts. Recent phase III clinical trials with belimumab in patients with
      active systemic lupus erythematosus (SLE) have been completed and achieved
      primary efficacy endpoints employing validated disease activity measures (SLEDAI
      and BILAG) as well as additional secondary endpoints related to disease flares
      and sparing of corticosteroid use. Significant decreases in numbers of activated
      B cells as well as levels of autoantibodies are observed during treatment with
      belimumab. The majority of observed clinical improvements are observed in
      musculoskeletal, mucocutaneous, and serologic domains of disease activity; the
      potential effects on more severe neurologic or renal domains of disease are not
      known. Treatment with belimumab is well tolerated and has not been associated
      with significant toxicity.

PMID- 22870476
TI  - Sodium oxybate: a potential new pharmacological option for the treatment of
      fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a common disorder, characterized by diffuse pain
      and tenderness, stiffness, fatigue, affective disorders and significant sleep
      pathology. A new set of diagnostic criteria have been developed which should make
      it easier for a busy clinician to diagnose the condition. US Food and Drug
      Administration (FDA) approved medications for the treatment of FMS have, for the
      most part, been geared to modulate the pain pathways to give the patient some
      degree of relief. A different kind of pharmacological agent, sodium oxybate
      (SXB), is described that is currently approved for the treatment of excessive
      daytime sleepiness and cataplexy in patients with narcolepsy. SXB, an endogenous
      metabolite of the inhibitory neurotransmitter gamma-hydroxybutyrate, is thought
      to act independently as a neurotransmitter with a presumed ability to modulate
      numerous other central nervous system neurotransmitters. In addition SXB has been
      shown to robustly increase slow wave sleep and decrease sleep fragmentation.
      Several large clinical trials have demonstrated SXB's ability to statistically
      improve pain, fatigue and a wide array of quality of life measurements of
      patients with fibromyalgia. SXB is not FDA approved to treat fibromyalgia.

PMID- 22870477
TI  - Management of chronic pain in the rheumatic diseases with insights for the
      clinician.
AB  - Pain that accompanies musculoskeletal conditions should be regarded as an illness
      entity in its own right and deserves treatment in parallel with the management of
      the underlying condition. Recent understanding of the pathophysiology of
      rheumatic pain invokes interplay of the nociceptive mechanisms driven by local
      tissue factors and the neurogenic responses that sustain chronic pain. In line
      with other pain conditions, ideal treatment of rheumatic pain should be through a
      multimodal approach, integrating nonpharmacologic as well as pharmacologic
      treatments. In the light of this new concept of pain mechanisms, future
      pharmacologic treatment options may encompass a wider scope than the use of
      traditional analgesics and nonsteroidal anti-inflammatory drugs. There is
      currently limited experience for use of pharmacologic treatments that act
      primarily on neurogenic mechanisms in rheumatic conditions. Drug combination
      studies are lacking, but this strategy seems clinically reasonable to allow for
      an approach to treating pain from different mechanistic perspectives. An added
      advantage would be the opportunity to use lower doses of individual drugs and
      thereby reduce the side effect profile. Ideal pain management must also include
      attention to the important co-associates of pain such as effects on sleep, mood
      and energy, which all have an impact on the global burden of suffering. Although
      complete relief of pain is still an unrealistic objective, reasonable outcome
      goals for symptom relief should be accompanied with an improvement in function.

PMID- 22870479
TI  - 'Old drugs for new applications': can orthopedic research benefit from this
      strategy?
AB  - New drug exploration is difficult in a clinical setting and the development of
      new drugs may be costly and time consuming. With further research into the
      pathological mechanisms and etiology of diseases as well as the rapid development
      of biological techniques, many 'old drugs' that have been applied in clinics may
      have new therapeutic functions which may shed light on clinical management. Based
      on this, we have investigated the 'old drugs for new applications' strategy in
      pharmacology which may be less expensive and more efficient in the clinical
      setting. In this paper we have explored and illustrated the potential
      applications of 'old drugs' for the treatment of orthopedic diseases, especially
      in arthritis and osteoporosis therapy.

PMID- 22870478
TI  - Osteoporosis in men: insights for the clinician.
AB  - Osteoporosis has finally been recognized as an important disorder in men. Men
      have osteoporotic fractures about 10 years later in life than women. Owing to
      increasing life expectancy, more fractures are predicted. Important risk factors
      for men include advancing age, smoking or chronic obstructive pulmonary disease,
      glucocorticoid therapy, and androgen deprivation therapy for prostate cancer.
      Other groups at risk for osteoporosis include those with alcohol abuse, men on
      enzyme-inducing antiseizure drugs, and those with malabsorption or history of
      surgery for peptic ulcer disease. History and physical examination will likely
      reveal secondary causes of osteoporosis. Some, but not all organizations,
      recommend screening for osteoporosis in men older than age 70. In the USA, The
      Department of Veterans Affairs recommends case finding rather than screening.
      Evaluation starts with bone mineral density testing by dual energy X-ray
      absorptiometry of the spine, hip, and in some cases forearm. A few laboratory
      tests can be helpful, including measurement of 25-hydroxyvitamin D. Most studies
      of osteoporosis therapy in men are small; but alendronate, risedronate,
      zoledronic acid, and teriparatide are FDA-approved to increase bone density in
      men with osteoporosis. A new potent antiresorptive agent, denosumab, increased
      bone density dramatically in men on androgen deprivation therapy and is approved
      for this indication in Europe. Recognition, diagnosis, and treatment of
      osteoporosis in men should lead to fewer fractures and probably fewer deaths.

PMID- 22870480
TI  - Simplifying Fibromyalgia Assessment: The VASFIQ Brief Symptom Scale.
AB  - OBJECTIVES: We tested the ability of the VASFIQ, a seven-item scale composed of
      Fibromyalgia Impact Questionnaire (FIQ) visual analog scales (VASs), to quantify
      fibromyalgia global disease severity and identify fibromyalgia patients with
      significant symptoms of fatigue, poor sleep, depression or anxiety. METHODS:
      Spearman rank correlations were used to compare global VASFIQ, FIQ and Patient
      Global Impression of Change (PGIC) scores and individual FIQ VAS scores with full
      length, validated questionnaire scores for fatigue (Multidimensional Assessment
      of Fatigue-Global Fatigue Index [MAF-GFI]), poor sleep (Medical Outcomes Study
      Sleep Problems Index [SPI]) and depression and anxiety (Hospital Anxiety and
      Depression Scale [HADS]). Patient scores used in the analyses were derived from
      2229 patients enrolled in three pregabalin fibromyalgia trials. Receiver
      operating characteristic analyses determined VASFIQ cutoff scores identifying
      patients with clinically significant symptom levels using full-length, validated
      symptom questionnaires to define cases. RESULTS: Global VASFIQ and FIQ scores
      correlated highly at baseline and study endpoints (rho = 0.94 and 0.97,
      respectively; both p<0.0001). Change in global VASFIQ and FIQ scores correlated
      similarly to PGIC scores at study endpoints (rho = 0.58 and 0.61, respectively;
      both p<0.0001). Individual FIQ VAS scores correlated with corresponding full
      length symptom questionnaire scores at baseline and study endpoints (VASfatigue
      with MAF-GFI, rho = 0.64 and 0.76; VASsleep with SPI, rho = 0.50 and 0.67;
      VASdepression with HADS-D, rho = 0.43 and 0.62; VASanxiety with HADS-A, rho =
      0.47 and 0.67, respectively; p <0.0001 for all). Patients with significant
      symptoms of fatigue were identified by VASfatigue >7.5, poor sleep by VASsleep
      >7.9, depression by VASdepression >5.8 and anxiety by VASanxiety >6.0. VASFIQ
      global scores >=31.4 and >=45.0 identified patients with moderate and severe
      global fibromyalgia symptoms, respectively. CONCLUSIONS: The VASFIQ scale
      accurately quantifies global fibromyalgia severity and identifies patients with
      significant symptoms of fatigue, poor sleep, depression or anxiety with brevity,
      enabling rapid patient assessment and informing treatment decisions in busy
      clinics.

PMID- 22870481
TI  - Improved Sleep Efficiency after Anti-Tumor Necrosis Factor alpha Therapy in
      Rheumatoid Arthritis Patients.
AB  - BACKGROUND: Poor sleep health is increasingly recognized as contributing to
      decreased quality of life, increased morbidity/mortality and heightened pain
      perception. Our purpose in this study was to observe the effect on sleep
      parameters, specifically sleep efficiency, in rheumatoid arthritis (RA) patients
      treated with anti-tumor necrosis factor alpha (anti-TNF-alpha) therapy. METHODS:
      This was a prospective observational study of RA patients with
      hypersomnolence/poor sleep quality as defined by the Epworth Sleepiness Scale
      (ESS) and Pittsburgh Sleep Quality Index (PSQI). Study patients underwent
      overnight polysomnograms and completed questionnaire instruments assessing sleep
      prior to starting anti-TNF-alpha therapy and again after being established on
      therapy. The questionnaire included the ESS, PSQI, the Berlin instrument for
      assessment of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS)
      diagnostic criteria, and measures of disease activity/impact. RESULTS: A total of
      12 RA patients met inclusion criteria, of which 10 initiated anti-TNF-alpha
      therapy and underwent repeat polysomnograms and questionnaire studies
      approximately 2 months later. Polysomnographic criteria for OSA were met by 60%
      of patients. Following anti-TNF-alpha therapy initiation, significant
      improvements were observed by polysomnography (PSG) for sleep efficiency,
      increasing from 73.9% (SD 13.5) to 85.4% (SD 9.6) (p = 0.031), and 'awakening
      after sleep onset' time, decreasing from 84.1 minutes (SD 43.2) to 50.7 minutes
      (SD 36.5) (p = 0.048). Questionnaire instrument improvements were apparent in
      pain, fatigue, modified Health Assessment Questionnaire (mHAQ), and Rheumatoid
      Arthritis Disease Activity Index (RADAI) scores. CONCLUSIONS: Improved sleep
      efficiency and 'awakening after sleep onset' time were observed in RA patients
      treated with anti-TNF-alpha therapy.

PMID- 22870482
TI  - Antiepileptics and bone health.
AB  - In recent years there has been increasing evidence suggesting that epilepsy and
      its treatment can have adverse effects on bone mineralization and calcium
      metabolism. Many studies have shown a significant reduction in bone mineral
      density (BMD) and an increased fracture risk in patients treated with enzyme
      inducing antiepileptics (phenobarbital, carbamazepine, phenytoin). It is assumed
      that CYP450-inducing antiepileptic drugs (AEDs) upregulate the enzymes which are
      responsible for vitamin D metabolism, with the effect of converting 25(OH)
      vitamin D into inactive metabolites, resulting in reduced calcium absorption with
      consecutive secondary hyperparathyroidism. Data on bone-specific effects of newer
      AEDs are limited; nevertheless, alterations of bone metabolism have been reported
      for oxcarbazepine, gabapentin and, in preclinical studies, for levetiracetam.
      Prophylactic administration of adequate amounts of calcium and vitamin D is
      recommended for all patients. For patients with long-term AED exposure, BMD
      measurement is recommended as part of osteoporosis investigation (especially for
      patients treated with enzyme-inducing AEDs and where there are major risk factors
      for fractures). Drug therapy (bisphosphonates) is reserved for the treatment of
      patients who have a high fracture risk; there are no specific intervention
      studies available in patients with epilepsy.

PMID- 22870483
TI  - Efficacy and safety of febuxostat in patients with hyperuricemia and gout.
AB  - The past decade has witnessed an exponential increase of novel therapeutic
      modalities for a variety of rheumatic disorders, including gout. During the past
      few years two novel therapeutic agents have been approved by the US Food and Drug
      Administration for the treatment of hyperuricemia in patients with gout, one of
      them being febuxostat, a nonpurine selective inhibitor of xanthine oxidase.
      Review of its pharmacokinetics and pharmacodynamics, efficacy and safety profile,
      and use in gout patients with comorbid conditions reveals that age and gender
      have no clinically significant effect and dose adjustments based on age or gender
      are not required. In addition, febuxostat can be used in patients with mild-to
      moderate renal or hepatic involvement. Its overall efficacy and safety profile is
      comparable and, in certain subsets such as gout patients with mild and moderate
      renal insufficiency, is superior to allopurinol.

PMID- 22870484
TI  - Novel treatments for systemic lupus erythematosus.
AB  - There are many new therapeutic directions for the disease systemic lupus
      erythematosus (SLE). Despite this, the US Food and Drug Administration (FDA) has
      approved only one biological agent and it involves B cells, now thought to play a
      significant role in the pathogenesis of SLE. The name of the drug is belimumab,
      which is an agent that removes the B-cell cytokine called B lymphocyte
      stimulation factor (BLyS). Rituximab did not achieve its primary endpoints, even
      though the consensus is that it may be effective in some forms of SLE including
      renal disease. The anticytokine therapies against interleukin (IL)-6, IL-10, IL
      17 and tumor necrosis factor (TNF) are effective in their own ways and phase II
      and III trials are in progress. Of particular interest to immunologists are the
      anti-interferon alpha and gamma drugs, which show promise in the animal models.
      Modulation of costimulatory molecules; specifically, the anti CD40, CTLA-***Ig
      and ICOS/B7RP blockade agents offer possibilities for the future using new
      pathways heretofore limited to rheumatoid arthritis. Finally, the use of tyrosine
      kinase inhibitors is another direction that has been successful in the inhibition
      of SLE in the murine model; early trials in human SLE have begun.

PMID- 22870485
TI  - A review of the efficacy and safety of denosumab in postmenopausal women with
      osteoporosis.
AB  - Denosumab, a fully human monoclonal antibody to RANK ligand [RANK-L]) was
      approved for the treatment of postmenopausal osteoporosis in June 2010, and is
      highly effective in reducing the risk of vertebral, nonvertebral, and hip
      fracture risk. The registration of denosumab was the culmination of the discovery
      and clarification of the internal bone microenvironment regulation of bone
      remodeling: the osteoblast-produced competitors: RANK-L and osteoprotogerin; and
      the osteoclast receptor: RANK. When RANK-L is upregulated in the estrogen
      deficient state and exceeds the amount of osteoprotogerin, there is an increase
      in osteoclastogenesis and bone resorption, and this is the major mechanism for
      bone mass loss and osteoporotic fractures in the postmenopausal state. The
      subsequent development of the human monoclonal antibody to RANK-L (denosumab) was
      the first product developed to reduce bone resorption by inhibiting RANK-L
      binding to RANK. Denosumab does not accumulate in bone, and has a unique
      pharmacokinetics so that its biological effect at the registered dose of 60 mg by
      subcutaneous injection every 6 months is no longer effective, at least as
      measured by an increase in the bone resorption marker collagen-cross-link C
      telopeptide and a decline in bone mineral density as measured by dual energy X
      ray absorptiometry. This unique pharmacokinetic profile thus suggests that in
      order to maintain the effectiveness of denosumab, continuous administration might
      be necessary. Extension of the registration trial ('FREEDOM') 5-year data
      indicates continued safety and efficacy, and will be extended to 10 years so that
      even longer-term data will be forthcoming. The profound but reversible
      suppression of bone turnover that is seen with denosumab partly explains the
      continuous increase in bone mineral density seen through 8 years of the phase II
      clinical trials. Denosumab offers a highly effective and safe parenteral therapy
      for osteoporosis and is being studied long term with the extension of the FREEDOM
      trial, and in other osteoporotic states - in men and glucocorticoid-induced
      osteoporosis.

PMID- 22870486
TI  - The efficacy and safety of tacrolimus in rheumatoid arthritis.
AB  - The crucial role of T cells in the pathogenesis of rheumatoid arthritis (RA) is
      well recognized. Tacrolimus is an immunomodulator that acts by the inhibition of
      T-cell activation. There have been numerous studies examining the use of
      tacrolimus in RA, including four randomized controlled trials. This article
      reviews these data with respect to the efficacy of the use of tacrolimus in RA as
      monotherapy and as part of combination therapy. The safety of tacrolimus use in
      RA is then evaluated. Tacrolimus is shown to be an effective and safe therapeutic
      option for RA patients intolerant of or resistant to previous disease-modifying
      antirheumatic drugs (DMARDs). In addition to monotherapy, tacrolimus has been
      successfully used as part of combination RA therapy, in particular in conjunction
      with methotrexate. Further assessment of combination approaches involving
      tacrolimus use alongside other DMARDs or biologics would be helpful. More studies
      are required to examine the effects of tacrolimus on the radiographic progression
      of RA.

PMID- 22870487
TI  - Soy foods: are they useful for optimal bone health?
AB  - Numerous studies have investigated the relationship between soy foods, soy
      protein, or isoflavone extracts and markers of bone health and osteoporosis
      prevention, and have come to conflicting conclusions. Research on dietary
      patterns, rather than on specific food ingredients or individual foods, may offer
      an opportunity for better understanding the role of soy foods in bone health.
      Evidence is reviewed regarding the question of whether soy foods contribute to a
      dietary pattern in humans that supports and promotes bone health. Soy foods are
      associated with improved markers of bone health and improved outcomes, especially
      among Asian women. Although the optimal amounts and types of soy foods needed to
      support bone health are not yet clear, dietary pattern evidence suggests that
      regular consumption of soy foods is likely to be useful for optimal bone health
      as an integral part of a dietary pattern that is built largely from whole plant
      foods.

PMID- 22870488
TI  - Atypical femur fractures: a review of the evidence and its implication to
      clinical practice.
AB  - Whilst bisphosphonates are an established modality in the treatment of
      osteoporosis, there have been increasing concerns regarding the risk of an
      unusual form of femur fracture amongst patients receiving bisphosphonates for
      prolonged periods. These fractures, referred to as 'atypical', have been
      characterized by a number of clinical and radiographic features that distinguish
      them from 'typical' osteoporotic fractures. The evidence base is currently split
      between a large number of case series demonstrating an association between the
      occurrence of atypical fractures and bisphosphonate use and several population
      based studies that do not confirm such an association. Hence, a degree of
      uncertainty surrounds this important issue. In this review, we examine the
      emerging evidence on atypical femur fractures, assess hypotheses on their
      biomechanical evolution and discuss the wider clinical implications of this
      phenomenon.

PMID- 22870489
TI  - Diagnosis and treatment of the idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies (IIMs) are rare disorders with the
      unifying feature of proximal muscle weakness. These diseases include
      polymyositis(PM), dermatomyositis (DM) and inclusion body myositis (IBM) as the
      most common. The diagnosis is based on the finding of weakness on exam, elevated
      muscles enzymes, characteristic histopathology of muscle biopsies,
      electromyography abnormalities and rash in DM. Myositis-specific antibodies have
      been helpful in defining subsets of patients with different responses to
      treatment and prognosis. The cornerstone of therapy is corticosteroids with the
      addition of other immunosuppressives in severe or refractory disease or patients
      with intolerable side effects. IBM is particularly difficult to treat but is more
      slowly progressive as compared with PM or DM. There is still a great need to find
      more effective and less-toxic therapies.

PMID- 22870490
TI  - Preference, satisfaction and usability of subcutaneously administered
      methotrexate for rheumatoid arthritis or psoriatic arthritis: results of a
      postmarketing surveillance study with a high-concentration formulation.
AB  - BACKGROUND/OBJECTIVES: This postmarketing surveillance study assessed the
      preference, satisfaction, usability, and tolerability of subcutaneous self
      administration of a high-concentration (50 mg/ml) ready-to-use formulation of
      methotrexate (MTX) in patients with rheumatoid arthritis or psoriatic arthritis.
      METHODS: The study enrolled 403 patients with rheumatoid or psoriatic arthritis.
      The first injection was administered by the attending physician or nurse,
      followed by five self-administered injections at weekly intervals. The high
      concentration formulation consisted of a prefilled syringe with MTX 50 mg/ml
      solution and a pre-attached needle. Questionnaires were used to document
      outcomes. RESULTS: The overall assessment was 'very good' and 'good' in 87.6% of
      the patients and in 92.8% of the physicians/study nurses. Availability and use of
      a pre-attached needle was considered as very advantageous and advantageous by
      91.8% of the patients and 88.8% of the physicians/study nurses. A total of 96% of
      the patients described the feeling of the injection as comfortable or tolerable.
      Patients reported that self-administration led to a feeling of more independence
      (89.1%) and an improved quality of life (83.6%). A total of 109 patients reported
      previous self-administration of low-concentration MTX formulations; 94.5% of them
      stated that they would prefer the high-concentration MTX formulation in the
      future. The formulation was generally well tolerated. Physicians' expectations
      concerning the benefit of switching to MTX self-administration was met in 92.8%
      of the patients. A total of 96.3% of the patients were considered suitable for
      subcutaneous self-administration of the MTX formulation. CONCLUSIONS: The 50
      mg/ml prefilled syringe appears to be a valuable treatment option for patients
      with rheumatoid and psoriatic arthritis in need of MTX. This is supported by the
      strong appreciation of the patients as well as their attending healthcare
      professionals for its convenience and tolerability. The results confirm the
      findings and experience from a clinical study performed in Germany in 2009, which
      showed that 93% of the patients prefer the 50 mg/ml prefilled syringe with a pre
      attached needle.

PMID- 22870491
TI  - Efficacy of vitamin E in knee osteoarthritis management of North Indian geriatric
      population.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common cause of chronic pain and
      disability in the elderly. It involves progressive destruction of articular
      cartilage as a consequence of various factors including augmented oxidative
      stress with advancing age which has not yet been controlled. It is conceivable
      that exogenous vitamin E supplementation ameliorates the modifiable indexes via
      regulation of free radical production and the consumption of antioxidant reserve.
      The objectives of the present study were to investigate the therapeutic effect of
      vitamin E supplementation in ameliorating the altered activity of antioxidant
      enzymes (superoxide dismutase, ceruloplasmin, glutathione peroxidase and
      catalase), erythrocyte malondialdehyde level (MDA, i.e. marker of lipid
      peroxidation) and markers of systemic inflammation (plasma C-reactive protein
      [CRP] and synovial fluid interleukin 6 [IL-6]) in osteoarthritic elderly.
      METHODS: Antioxidant enzymes status, MDA, IL-6 and CRP levels were estimated by
      using standard methods in 40 healthy individuals (control group) and in 40
      osteoarthritic patients aged 50-70 years before and after 3 months of vitamin E
      supplementation, i.e. group I (nonsupplemented) and group II (200 mg/day vitamin
      E supplemented). The obtained values were compared statistically by using
      Student's t-test. RESULTS: Marked alteration in antioxidant enzymes, MDA and
      inflammatory markers were observed in group I (p < 0.05) as compared with
      controls. These levels were ameliorated significantly after vitamin E
      supplementation (p < 0.05) in group II. However, elevated levels of serum CRP and
      synovial fluid IL-6 (r = 0.034; p < 0.05) were decreased insignificantly (p <
      0.1) after vitamin E supplementation in knee OA patients. CONCLUSIONS: These
      findings confirm the protective role of vitamin E supplementation against
      oxidative stress mediated biomolecular deterioration in OA. However, the anti
      inflammatory role of vitamin E remains to be explored.

PMID- 22870492
TI  - Bazedoxifene: the evolving role of third-generation selective estrogen-receptor
      modulators in the management of postmenopausal osteoporosis.
AB  - Osteoporosis is a significant public health concern, particularly for
      postmenopausal women. Current treatment options may not be appropriate for all
      women. Selective estrogen-receptor modulators (SERMs) are a class of molecules
      with tissue-selective activity. Bazedoxifene is currently in clinical development
      for the prevention and treatment of postmenopausal osteoporosis. In a 2-year,
      phase III, osteoporosis prevention study (N = 1583), bazedoxifene 10, 20, and 40
      mg was shown to preserve bone mineral density and decrease biochemical markers of
      bone turnover compared with placebo in postmenopausal women at risk for
      osteoporosis. In a pivotal 3-year, phase III, osteoporosis treatment study (N =
      7492), bazedoxifene 20 and 40 mg significantly reduced the incidence of new
      vertebral fractures compared with placebo (p < 0.05 for both) in postmenopausal
      women with osteoporosis. In a post hoc subgroup analysis of women at higher risk
      for fracture (n = 1772), bazedoxifene 20 mg significantly reduced the risk of
      nonvertebral fractures versus placebo (p = 0.02) and raloxifene 60 mg (p = 0.05).
      Bazedoxifene 20 mg has demonstrated sustained efficacy in reducing the risk of
      vertebral fractures over 5 and 7 years. Overall, bazedoxifene was generally safe
      and well tolerated, with favorable endometrial and breast safety profiles. As
      with other SERMs, the rate of deep vein thrombosis was higher in the bazedoxifene
      groups compared with placebo at 3 and 5 years. Considering its demonstrated
      efficacy and safety, bazedoxifene may be an appropriate osteoporosis therapy for
      women who cannot take or are unwilling to take bisphosphonates because of safety
      or tolerability issues. Bazedoxifene may also be appropriate for younger women at
      increased fracture risk who are concerned about the effects of long-term
      bisphosphonate therapy. This article reviews the results of key clinical trials
      of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis
      and describes its role in clinical practice.

PMID- 22870493
TI  - Treatment of rheumatoid arthritis in patients with concomitant chronic hepatitis
      C infection.
AB  - Hepatitis C virus (HCV) infection is present in 1.8% of the general US population
      and its prevalence worldwide is estimated at 2-3%. HCV infected patients with
      concomitant rheumatoid arthritis (RA) pose a particular challenge to the
      rheumatologist because of the risks of treatment with disease-modifying
      medications in patients with chronic liver infection. In this paper the
      difficulties of diagnosing RA in HCV patients and the safety of RA treatment in
      patients with both conditions are discussed.

PMID- 22870494
TI  - Juvenile dermatomyositis: new insights and new treatment strategies.
AB  - Juvenile dermatomyositis (JDM) is a rare but complex and potentially life
      threatening autoimmune disease of childhood, primarily affecting proximal muscles
      and skin. Although the cause of JDM remains unknown it is clear that genetic and
      environmental influences play a role in the aetiology. In contrast to adults with
      dermatomyositis, children with JDM are more likely to have complications that are
      thought to indicate a vasculopathic process, such as severe skin disease, with
      ulceration or calcinosis, gut vasculopathy or central nervous system disease. New
      treatments are much needed and are becoming available and being tested through
      international multicentre trials. This review will focus on recent insights into
      pathogenesis, the assessment of the disease in children and the modern approach
      to its treatment.

PMID- 22870495
TI  - Is there a future for selective estrogen-receptor modulators in osteoporosis?

PMID- 22870496
TI  - Aging and bone loss: new insights for the clinician.
AB  - It is well known that the underlying mechanisms of osteoporosis in older adults
      are different than those associated with estrogen deprivation. Age-related bone
      loss involves a gradual and progressive decline, which is also seen in men.
      Markedly increased bone resorption leads to the initial fall in bone mineral
      density. With increasing age, there is also a significant reduction in bone
      formation. This is mostly due to a shift from osteoblastogenesis to predominant
      adipogenesis in the bone marrow, which also has a lipotoxic effect that affects
      matrix formation and mineralization. We review new evidence on the
      pathophysiology of age-related bone loss with emphasis upon the mechanism of
      action of current osteoporosis treatments. New potential treatments are also
      considered, including therapeutic approaches to osteoporosis in the elderly that
      focus on the pathophysiology and potential reversal of adipogenic shift in bone.

PMID- 22870498
TI  - Juvenile idiopathic arthritis: management and therapeutic options.
AB  - THE GOALS OF TREATMENT FOR JUVENILE IDIOPATHIC ARTHRITIS (JIA) INCLUDE:
      suppression of inflammation, achievement of remission, relief of pain,
      maintenance of function and doing so with minimal toxicity. Important discoveries
      over the past 10-15 years have led to more targeted treatments for children with
      JIA. The International League of Associations for Rheumatology (ILAR)
      classification system for childhood arthritides, better assessment tools for
      clinical response, improved definitions of remission, new imaging techniques and
      evidence in gene expression profiling have all contributed to the development of
      more targeted treatments. Nonsteroidal anti-inflammatory agents still have a role
      in mild disease and intra-articular steroid injections continue to be used most
      commonly in patients with oligoarticular JIA. Disease-modifying agents such as
      methotrexate have demonstrated efficacy and safety; however, in many patients,
      the disease remains active despite this treatment. These children now receive
      more targeted treatment including the tumor necrosis factor alpha (TNFalpha)
      inhibitors, interleukin-1 blockade, interleukin-6 blockade, selective
      costimulation modulators and selective B-cell blockade. The biologic targeted
      therapies have changed the strategy in which we treat our children with JIA;
      however, there remains much to be learned about the long-term effects and safety
      of these medicines.

PMID- 22870499
TI  - Diagnosis and treatment of inflammatory myopathy: issues and management.
AB  - The idiopathic inflammatory myopathies include polymyositis (PM), dermatomyositis
      (DM) and inclusion body myositis (IBM). The specific etiologies of these muscle
      diseases are not well known and are thought to involve components of the humoral
      and cellular immune system as well as other nonimmune factors. Diagnosing these
      myopathies involves a laboratory evaluation, imaging studies, multidisciplinary
      consultations, histologic examination and potentially genetic studies. Despite
      all that we currently know about inflammatory muscle disease with these studies,
      we find that our current concept of muscle disease is changing. In the cases of
      immune-mediated necrotizing myopathy and inclusion body myositis, the concept of
      inflammation needs to be rethought. Moreover, the classification schemes for
      these idiopathic myopathies may need updating to include current research
      findings that relate to pathogenesis. With ongoing discoveries, classification
      and appropriate treatment is becoming increasingly challenging. This paper
      discusses the inflammatory myopathies, the challenges to diagnosis,
      classification controversies and potential treatment options.

PMID- 22870497
TI  - Use magnetic resonance imaging to assess articular cartilage.
AB  - Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional
      assessment of the entire joint, simultaneously allowing the direct visualization
      of articular cartilage. Thus, MRI has become the imaging modality of choice in
      both clinical and research settings of musculoskeletal diseases, particular for
      osteoarthritis (OA). Although radiography, the current gold standard for the
      assessment of OA, has had recent significant technical advances, radiographic
      methods have significant limitations when used to measure disease progression.
      MRI allows accurate and reliable assessment of articular cartilage which is
      sensitive to change, providing the opportunity to better examine and understand
      preclinical and very subtle early abnormalities in articular cartilage, prior to
      the onset of radiographic disease. MRI enables quantitative (cartilage volume and
      thickness) and semiquantitative assessment of articular cartilage morphology, and
      quantitative assessment of cartilage matrix composition. Cartilage volume and
      defects have demonstrated adequate validity, accuracy, reliability and
      sensitivity to change. They are correlated to radiographic changes and clinical
      outcomes such as pain and joint replacement. Measures of cartilage matrix
      composition show promise as they seem to relate to cartilage morphology and
      symptoms. MRI-derived cartilage measurements provide a useful tool for exploring
      the effect of modifiable factors on articular cartilage prior to clinical disease
      and identifying the potential preventive strategies. MRI represents a useful
      approach to monitoring the natural history of OA and evaluating the effect of
      therapeutic agents. MRI assessment of articular cartilage has tremendous
      potential for large-scale epidemiological studies of OA progression, and for
      clinical trials of treatment response to disease-modifying OA drugs.

PMID- 22870502
TI  - Carbon nanotube immobilized polar membranes for enhanced extraction of polar
      analytes.
AB  - We demonstrate for the first time that carbon nanotubes (CNTs) can be readily
      immobilized on the surface of a solid polymeric membrane which can lead to
      enhanced enrichment factor and extraction efficiency. The effectiveness of the
      CNT mediated process is demonstrated by micro-scale membrane extraction via
      direct solvent enrichment of polar and nonpolar organics. The enrichment factor
      measured as the ratio of concentrations in the acceptor to the donor phases was
      as high as 282 and the enhancement over the unmodified membrane was as much as
      92%. In addition, the solvent retention in the carbon nanotube immobilized
      membrane (CNIM) increased by as much as 29%. Overall, the CNT incorporation
      provided enhanced solute transport and thus led to overall performance
      enhancement.

PMID- 22870501
TI  - Molecularly imprinted photonic polymer as an optical sensor to detect
      chloramphenicol.
AB  - An inverse opal photonic crystal sensor that could specifically detect
      chloramphenicol (CAP) in a label-free way was introduced in the current research.
      A colloidal crystal template was first prepared from monodisperse SiO(2)
      nanospheres. Precursors with different compositions were infused into the void
      spaces of the respective templates and aggregated. The template and the imprinted
      CAP were removed, and a molecularly imprinted photonic polymer (MIPP) with
      numerous nanocavities derived from the SiO(2) template was prepared. The MIPP
      could specifically recognize the target CAP. The results showed that the
      embedding and transporting of CAP could change the reflection peak intensity of
      the MIPP. The MIPP exhibited good responsiveness, with a detection range from 1
      ng mL(-1) to 1 MUg mL(-1) of CAP. The MIPP response time was 8 min upon its
      addition to CAP at a concentration of 10 ng mL(-1), which is shorter than that of
      other methods. After repeated use, the MIPP maintained a good performance and
      detection capacity. Thus, the results prove that the novel sensor could
      specifically detect CAP in a simple, time-saving, and low-cost manner.

PMID- 22870500
TI  - Treatment and management of pseudogout: insights for the clinician.
AB  - Pseudogout and the associated calcium pyrophosphate dihydrate (CPPD)- crystal
      related arthropathies are common conditions that present particular management
      problems in clinical practice as they often affect older patients with multiple
      medical comorbidities. The epidemiology, metabolic and endocrine disease
      associations, and routine investigations used in the diagnostic workup are
      briefly reviewed. Current treatment approaches that are mainly directed at
      relieving the symptoms of joint inflammation are outlined. Unlike gout, there are
      no agents available that have been shown to decrease crystal load in CPPD-related
      joint disease. Recent novel insights into the pathogenesis of crystal-induced
      joint inflammation and subsequent joint degeneration are also discussed. The
      potential of colchicine as a prophylactic agent in managing recurrent attacks and
      the likely mechanisms of its effects on the NACHT, LRR and PYD domains-containing
      protein 3 (NALP-3) inflammasome of the innate immune system are highlighted. The
      use of agents that directly target the inflammasome, in particular drugs which
      inhibit the interleukin 1 pathway, in the treatment of severe, refractory
      pseudogout is also discussed. Finally, there is particular emphasis on the likely
      pathogenic role of CPPD crystal deposition in degenerative joint disease and the
      use of targeted anticrystal therapies as potential disease-modifying drugs.

PMID- 22870503
TI  - Multivariate optimization of mercury determination by flow injection-cold vapor
      generation-inductively coupled plasma optical emission spectrometry.
AB  - In this work a procedure for mercury determination by Flow Injection-Cold Vapor
      Generation-Inductively Coupled Plasma Optical Emission Spectrometry (FI-CVG-ICP
      OES) has been developed. The system uses a small homemade glass separator
      constructed to drive the Hg vapor to the plasma. An evolutionary operation
      factorial design was used to evaluate the optimal experimental conditions for
      mercury vapor generation, aiming at the low consumption of reagents, the
      improvement of the analytical signal and consequently greater sensitivity. The
      procedure allowed the determination of mercury and showed excellent linearity for
      the concentration range from 0.50 MUg L(-1) to 100.0 MUg L(-1), with Limits of
      Detection (LOD) and Quantification (LOQ) of 0.11 MUg L(-1) and 0.36 MUg L(-1),
      respectively, and a sampling rate of 36 analyses per hour. The optimized
      procedure showed good accuracy and precision, and the method was validated by the
      analysis of two certified reference materials: Buffalo River Sediment (NIST 2704)
      and human hair (IAEA 085). A good agreement with the certified values was
      achieved, with recovery values of 99% and 98% and relative standard deviation
      close to 2%.

PMID- 22870504
TI  - A turn-on and reversible fluorescence sensor for zinc ion.
AB  - A simple Schiff base type fluorescent receptor was prepared and evaluated for its
      fluorescence response to heavy metal ions. Receptor 1 exhibits an "off-on-type"
      mode with high selectivity in the presence of Zn(2+) ion. The addition of EDTA
      quenches the fluorescence of receptor 1-Zn(2+) complex, making receptor 1 a
      reversible chemosensor. The selectivity of 1 for Zn(2+) is the consequence of
      combined effects of CHEF, C=N isomerization and inhibition of ESIPT.

PMID- 22870505
TI  - Solid oxide fuel cells with both high voltage and power output by utilizing
      beneficial interfacial reaction.
AB  - An intriguing cell concept by applying proton-conducting oxide as the ionic
      conducting phase in the anode and taking advantage of beneficial interfacial
      reaction between anode and electrolyte is proposed to successfully achieve both
      high open circuit voltage (OCV) and power output for SOFCs with thin-film
      samarium doped ceria (SDC) electrolyte at temperatures higher than 600  degrees
      C. The fuel cells were fabricated by conventional route without introducing an
      additional processing step. A very thin and dense interfacial layer (2-3 MUm)
      with compositional gradient was created by in situ reaction between anode and
      electrolyte although the anode substrate had high surface roughness (>5 MUm),
      which is, however, beneficial for increasing triple phase boundaries where
      electrode reactions happen. A fuel cell with Ni-BaZr(0.4)Ce(0.4)Y(0.2)O(3) anode,
      thin-film SDC electrolyte and Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-delta) (BSCF)
      cathode has an OCV as high as 1.022 V and delivered a power density of 462 mW cm(
      2) at 0.7 V at 600  degrees C. It greatly promises an intriguing fuel cell
      concept for efficient power generation.

PMID- 22870506
TI  - Computational enzymatic catalysis--clarifying enzymatic mechanisms with the help
      of computers.
AB  - Enzymes play a biologically essential role in performing and controlling an
      important share of the chemical processes occurring in life. However, despite
      their critical role in nature, attaining a clear understanding of the way an
      enzyme acts, i.e. its catalytic mechanism, is a cumbersome task that requires the
      cooperative efforts of a large number of different scientific techniques.
      Computational methods offer a particularly insightful way to study such
      mechanisms, always beautifully complementing the information arising from
      experimental techniques and working as an excellent alternative for assessing the
      viability of different mechanistic proposals. This review highlights two
      important computational strategies to study enzymatic catalysis - the cluster
      modeling approach and the hybrid quantum mechanical/molecular mechanical (QM/MM)
      method - complemented with a selection of hand-picked examples of our own work.

PMID- 22870507
TI  - Effect of heavy water on phospholipid membranes: experimental confirmation of
      molecular dynamics simulations.
AB  - Although there were experimental indications that phospholipid bilayers hydrated
      with D(2)O express different biophysical properties compared with hydration by
      ordinary H(2)O, a molecular concept for this behavior difference was only
      recently proposed by a molecular dynamics simulations study [T. Rog et al., J.
      Phys. Chem. B, 2009, 113, 2378-2387]. Here we attempt to verify those theoretical
      predictions by fluorescence measurements on 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      membranes. Specifically, we determine the water isotope effect on headgroup
      hydration and mobility, lateral lipid diffusion and lipid backbone packing. Time
      dependent fluorescence shift experiments show significantly slower dynamics and
      lower hydration of the headgroup region for a bilayer hydrated with D(2)O, an
      observation in good agreement with the calculated predicted differences in
      duration of lipid-lipid and lipid-water bridges and extent of water penetration
      into the bilayer, respectively. The water isotope effect on the lipid order
      parameter of the bilayer core (measured by fluorescence anisotropy) and lateral
      diffusion of lipid molecules (determined by two-focus fluorescence correlation
      spectroscopy) is close to the experimental errors of the experiments, however
      also refers to slightly more rigid organization of phospholipid bilayers in heavy
      water. This study confirms the view that the water isotope effect can be
      particularly found in time-resolved physicochemical properties of the membrane.
      Together with the simulations our experiments provide a comprehensive, molecular
      view on the effect of D(2)O on phospholipid bilayers.

PMID- 22870508
TI  - New insight into the electrochemical desorption of alkanethiol SAMs on gold.
AB  - A combination of Polarization Modulation Infrared Reflection Absorption
      Spectroscopy (PMIRRAS) under electrochemical control, Electrochemical Scanning
      Tunneling Microscopy (ECSTM) and Molecular Dynamics (MD) simulations has been
      used to shed light on the reductive desorption process of dodecanethiol (C12) and
      octadecanethiol (C18) SAMs on gold in aqueous electrolytes. Experimental PMIRRAS,
      ECSTM and MD simulations data for C12 desorption are consistent with formation of
      randomly distributed micellar aggregates stabilized by Na(+) ions, coexisting
      with a lying-down phase of molecules. The analysis of pit and Au island coverage
      before and after desorption is consistent with the thiolate-Au adatoms models. On
      the other hand, PMIRRAS and MD data for C18 indicate that the desorbed
      alkanethiolates adopt a Na(+) ion-stabilized bilayer of interdigitated
      alkanethiolates, with no evidence of lying down molecules. MD simulations also
      show that both the degree of order and tilt angle of the desorbed alkanethiolates
      change with the surface charge on the metal, going from bilayers to micelles.
      These results demonstrate the complexity of the alkanethiol desorption in the
      presence of water and the fact that chain length and counterions play a key role
      in a complex structure.

PMID- 22870509
TI  - Effect of biological confinement on the photophysics and dynamics of a proton
      transfer phototautomer: an exploration of excitation and emission wavelength
      dependent photophysics of the protein-bound drug.
AB  - The present work demonstrates the effect of biological confinement on the
      photophysics and dynamics of a bio-active drug molecule viz., 5-chlorosalicylic
      acid (5ClSA). 5ClSA is a potential candidate exhibiting Excited-State
      Intramolecular Proton Transfer (ESIPT) reaction and thereby generating the
      phototautomer (i.e. proton transferred keto form) in the excited state. Given the
      pK(a) of 5ClSA (around 2.64), the anionic form of the drug molecule is expected
      to be the interacting species with the protein under the experimental conditions
      (buffered solution of pH 7.40). The ESIPT photophysics of the drug (5ClSA anion)
      is found to be remarkably modified within the confined bio-environment of a model
      transport protein Bovine Serum Albumin (BSA) in terms of remarkable emission
      intensity enhancement coupled with a discernible red-shift of the emission
      maximum wavelength. Such considerable modification of the ESIPT photophysics of
      the 5ClSA anion has been exploited to determine the drug-protein binding strength
      (as characterized by the binding constant K (+/-10%) = 6.11 * 10(2) M(-1)). The
      present work also delves into evaluation of the probable binding location of the
      drug within the biomacromolecular assembly of the protein by a blind docking
      simulation technique, which reveals hydrophobic subdomain IIA to be the probable
      binding site of the drug. Circular dichroism (CD) spectroscopy delineates the
      effect of drug binding on the protein secondary structure in terms of decrease of
      alpha-helical content of BSA with increasing drug concentration. Apart from this,
      the excitation-emission matrix fluorescence technique is found to hint at the
      effect on protein tertiary structure upon binding to the drug. Chaotrope-induced
      protein denaturation has been explored to complement the findings on the binding
      interaction process. The modulated dynamics of the proton transfer phototautomer
      of the 5ClSA anion within the biological confinement is also investigated in this
      context to explore the slower rate of solvent-relaxation dynamics.

PMID- 22870510
TI  - NHS shadowing scheme not enough to keep patients safe.

PMID- 22870511
TI  - The final push for polio eradication?

PMID- 22870512
TI  - Searching for dignity.

PMID- 22870513
TI  - Life in the serendipitous lane: excitement and gratification in studying DNA
      repair.

PMID- 22870514
TI  - My path toward DNA repair.

PMID- 22870515
TI  - ECG of the month: a subtle sign of dual atrioventricular nodal pathways. Sinus
      rhythm with second-degree atrioventricular (AV) block, Type I, with each
      Wenckebach sequence being terminated by a premature, retrograde, reentrant P
      wave; left ventricular hypertrophy with repolarization changes.

PMID- 22870516
TI  - A heart-beat is amplified and then resonates in history.

PMID- 22870517
TI  - An interbreeding of Germanic and Mediterranean words.

PMID- 22870518
TI  - Equipping yourself to cope with change.

PMID- 22870519
TI  - Hip arthroplasty - orthopedic surgery of the 20th  century.

PMID- 22870520
TI  - Abstracts of the Medical Oncology Group of Australia Incorporated Annual
      Scientific Meeting and the 5th Annual COGNO (Cooperative Trials Group for Neuro
      Oncology) Annual Scientific Meeting. August 8-10, 2012. Brisbane, Queensland,
      Australia.

PMID- 22870521
TI  - [Application of bispectral index monitoring in intensive care unit].

PMID- 22870522
TI  - [Na+-K+-Cl- cotransporter-1 in brain edema].

PMID- 22870523
TI  - Addressing misconnection dangers.

PMID- 22870524
TI  - T cell signaling goes with the flow.

PMID- 22870525
TI  - Ionizing radiation.

PMID- 22870526
TI  - F-actin flow regulates T cell activation.

PMID- 22870527
TI  - Report from the biennial scientific meeting of the Australasian section of the
      American Oil Chemists Society (AAOCS) held in Adelaide, November 2011.

PMID- 22870528
TI  - Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion
      of the circle of Willis).

PMID- 22870530
TI  - Protect our jobs. It's in your hands.

PMID- 22870529
TI  - How politicians try to give the illusion that they're helping the people they
      represent.

PMID- 22870531
TI  - Pro-patient vs. pro-profit. Change in Michigan hospitals means change for
      Michigan nurses.

PMID- 22870532
TI  - Are you at risk for compassion fatigue?

PMID- 22870533
TI  - Hypofractionated radiation therapy for prostate cancer: risks and potential
      benefits in a fiscally conservative health care system.
AB  - Prostate cancer is the second most common cause of cancer death in American men
      and represents a significant factor in US health care costs. Radiation therapy
      serves as one of the most effective treatments for prostate cancer. However,
      radiation is also an expensive treatment modality and is a significant
      contributor to the overall rise in the cost of prostate cancer care. Currently,
      standard external beam radiation therapy for prostate cancer consists of between
      75.6 and 81.0 Gy of radiation separated into 1.8- to 2-Gy doses (or "fractions")
      given daily for between 7 and 9 weeks. Recently, relatively shorter treatment
      schedules delivering more radiation per treatment-consisting of fractions > 2 Gy
      over shorter time periods have been proposed in an effort to curtail rising
      health care costs and improve patient convenience. However, significant
      uncertainty still remains regarding outcomes from this type of more condensed
      treatment, known as"hypofractionated"radiation. In this article, we provide the
      historical background and rationale for hypofractionated prostate cancer
      treatment, discuss the potential benefits and risks of prostate
      hypofractionation, and review the clinical evidence regarding the effectiveness
      of hypofractionated radiation therapy for prostate cancer.

PMID- 22870534
TI  - Hypofractionated radiotherapy for prostate cancer: has the time come?

PMID- 22870535
TI  - Less is more: will hypofractionated radiotherapy negatively affect cancer centers
      or be a Godsend in the new health care environment?

PMID- 22870536
TI  - Integrating innovative therapeutic strategies into the management of renal cell
      carcinoma.
AB  - Three emerging trends have occurred recently in renal cell carcinoma (RCC).
      First, over the last several decades there has been a marked increase in the
      diagnosis of RCC, with a corresponding decrease in the typical tumor size,
      resulting in an increased interest in less invasive approaches to primary tumor
      treatment. Second, while conventional radiotherapy plays a limited palliative
      role due to the relative radio-resistance of RCC, advances in immobilization and
      image guidance have led several investigators to consider stereotactic
      radiotherapy techniques (SRT) to overcome this resistance, with impressive
      results in the metastatic setting. In addition, preliminary use of SRT to treat
      the primary RCC tumor is underway. Thirdly, although RCC is resistant to
      conventional chemotherapy agents, exciting recent advances have emerged in the
      treatment of clear cell RCC, with the development of targeted agents in addition
      to immunotherapy-based treatments. In the current critical review we discuss
      these emerging trends in localized and systemic treatment as well as possible
      interesting combinations of the two modalities. Finally, we discuss the role of
      the new systemic agents in non-clear cell RCC.

PMID- 22870537
TI  - Integration of newer strategies into the management of RCC.

PMID- 22870538
TI  - A urologic perspective on management of localized and metastatic RCC.

PMID- 22870539
TI  - Adjuvant endocrine therapy for breast cancer.
AB  - Endocrine therapy is a critical part of adjuvant therapy in women with hormone
      receptor-positive breast cancer, and has been shown to reduce the risk of
      recurrence and death from breast cancer. For decades, 5 years of tamoxifen has
      been the standard treatment. For premenopausal women, it remains so, and we await
      the results of ongoing trials to define the role of ovarian suppression or
      ablation with endocrine therapy. If a woman becomes postmenopausal during
      treatment, consideration should be given to extended adjuvant therapy with an
      aromatase inhibitor (AI) for another 5 years. In postmenopausal women, trials
      have shown that AIs are more beneficial than tamoxifen in preventing disease
      recurrence.They have been compared as upfront treatment for 5 years, as
      sequential therapy after 2 to 3 years of tamoxifen, and as extended treatment for
      5 years after 5 years of tamoxifen. Among the questions still being studied are
      the optimal duration of extended adjuvant therapy with AIs, how one AI performs
      compared to another, and whether there is a benefit to intermittent extended
      adjuvant treatment.

PMID- 22870540
TI  - Historical and cultural determinants in the evolution of adjuvant endocrine
      therapy: a tale of two hemispheres, separated by a common language.

PMID- 22870541
TI  - Adjuvant endocrine therapy for breast cancer: a commentary.

PMID- 22870542
TI  - The neutropenic diet reviewed: moving toward a safe food handling approach.
AB  - For decades, the concept of a neutropenic diet has implied a strict limitation of
      foods allowed for consumption, as a presumptive means of reducing the risk of
      infection in cancer patients. The rationale was to limit the introduction of
      potentially harmful bacteria into the gastrointestinal tract by the restriction
      of certain foods that might harbor those organisms. However, this concept has not
      been substantiated with direct proof, and no universal definition of the
      neutropenic diet exists. Exactly which foods are restricted varies greatly by
      institution, but most notable is the restriction of fresh fruits and vegetables.
      Research evaluating potential benefits of a neutropenic diet is very limited, but
      the diet is still prescribed in many institutions with the hope that it will
      prevent foodborne infection and/or bacteremia in neutropenic patients. Review of
      the pathophysiology of foodborne illness and pertinent studies about the
      neutropenic diet lead to the conclusion that there is no clear benefit from the
      longstanding dietary restrictions that may be imposed during neutropenia.
      Instead, we propose adoption of standard safe food handling methods to allow for
      a more liberalized diet in the neutropenic patient.

PMID- 22870543
TI  - Eat your vegetables.

PMID- 22870544
TI  - The neutropenic diet... still ageless?

PMID- 22870545
TI  - Developing a culture of giving in Tennessee.

PMID- 22870546
TI  - Presidents address 2012.

PMID- 22870547
TI  - A technique to determine the preferred use of a custom abutment for an implant
      supported crown.
AB  - One of the most significant challenges in contemporary dental implant therapy
      involves managing the transition of the restoration from the implant through the
      soft tissues by means of an abutment. This article presents a practical technique
      to visualize if the selection of a custom-made abutment would be favored over the
      use of a manufactured standard abutment to receive crown restoration supported by
      a dental implant.

PMID- 22870548
TI  - Integrating the CEREC technology at UT College of Dentistry.
AB  - The computer-aided design/computer-aided manufacturing (CAD/CAM) has evolved
      during the past 25 years, and this evolution has improved the speed and precision
      in which dentists can deliver high quality esthetic restorations. CEREC is an
      acronym for "ceramic reconstruction" and is one of the CAD/CAM systems available
      to dentists in private practice. The University of Tennessee College of Dentistry
      was one of the first dental schools in the United States to embrace this
      technology and integrate it into the four-year curriculum. In a dental school
      setting, this technology can prove to be an educational tool for the dental
      students, cost effective for the University and provide exceptional service for
      the patients.

PMID- 22870549
TI  - Gummy smile: could it be genetic? Hereditary gingival fibromatosis.
AB  - Gingival enlargement is common among patients and can be caused by a variety of
      etiological factors. The most common reason is poor oral hygiene and high
      bacterial load that leads to gingival inflammation and enlargement. Other
      implicated factors include systemic drugs, such as phenytoin (Dilantin) taken by
      epileptic patients, calcium channel blockers such as nifedipine (Procardia) and
      verapamil (Calan) for the treatment of hypertension, arrhythmia and angina.
      Another class of medication associated with gingival enlargement is
      immunosuppressive agents given to organ-transplant patients to prevent rejection
      of the new element such as cyclosporine. Some enlargements could be associated
      with other conditions such as puberty, pregnancy or diabetes or be a symptom of a
      systemic disease (leukemia, Wegener's granulomatosis or sarcoidosis). In rare
      cases the cause for the enlargement is genetic and termed hereditary gingival
      fibromatosis (HGF). HGF is a genetic disorder characterized by a progressive
      enlargement of the gingiva. Histologically, the gingiva is characterized by an
      accumulation of dense fibrous connective tissue. This is believed to be due to an
      imbalance between synthesis and degradation of extracellular matrix composed
      mainly of collagen molecules or due to an alteration in fibroblast proliferation.
      Different pathogenic mechanisms have been proposed and examined over the years
      but no precise process has been identified. The main objective of this paper is
      to discuss this genetic anomaly and support it with clinical cases of a mother
      and her two children. It will focus on the clinical and histologic
      characteristics of HGF as well as known biologic and genetic features and
      treatment modalities.

PMID- 22870550
TI  - Mandibular abnormalities in a patient with neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by
      the presence of cutaneous neurofibromas, multiple cafd-au-lait spots and
      pigmented nodules of the iris known as Lisch nodules. In some cases, the
      diagnosis can be made at birth while in others the diagnosis is made later in
      life based on the appearance of additional criteria. We describe radiographic
      abnormalities of the mandible in a young adult male with NF1.

PMID- 22870551
TI  - Short-term objective and subjective evaluation of small-diameter implants used to
      support and retain mandibular prosthesis.
AB  - BACKGROUND: The introduction of small-diameter implants has provided dentists the
      means of providing edentulous and partially edentulous patients with immediate
      functioning transitional prostheses while definitive restorations are being
      fabricated. The successful use of these small-diameter implants for temporary
      stabilization of prostheses has led many clinicians to explore the option of
      using them as a definitive alternative, especially as the technique requires
      minimal time and also is economical for the patients. To date, there has been no
      study with multiple patients looking at both the subjective and objective
      outcomes of these small-diameter implants. MATERIALS AND METHODS: Twenty-seven
      edentulous patients were enrolled in this study, seven of them were smokers. One
      hundred and eight small-diameter (2.0 mm, MDL) implants were surgically placed in
      24 edentulous mandibles. All implants were immediately loaded. The patients
      filled out a screening questionnaire and four subsequent questionnaires to test
      their satisfaction with the altered prosthesis at 6, 12, 18 and 24 months. The
      survival of the implants was also noted. RESULTS: Smokers had an implant survival
      of 79%. Non-smokers had an implant survival of 100%. The results of the
      questionnaire indicated an overall satisfaction with the implant-supported
      prosthesis.

PMID- 22870552
TI  - Integrating behavioral health records into EHRs.

PMID- 22870553
TI  - Research doesn't support mandatory influenza vaccination.

PMID- 22870554
TI  - Community members address health care challenges during hack-a-thon.

PMID- 22870555
TI  - The potential and pitfalls of geocoding electronic health records.
AB  - BACKGROUND: Geocoding electronic health records (EHRs) provides novel insights
      for clinicians, but it is important to understand and address key issues,
      including privacy and protection of patient records, in order to realize
      potential benefits. METHODS: This paper discusses the issues surrounding
      geocoding and illustrates potential benefits through 3 case studies of no-shows
      to clinical appointments, patient analysis for a merged clinic site, and multi
      clinic patient overlap. CONCLUSION: Geocoding EHRs provides a new contextual
      understanding for clinicians to understand patients and provide targeted
      interventions that patients can implement. While geocoding EHRs presents a need
      for high data security, the benefits outweigh the risks when proper protections
      are observed.

PMID- 22870556
TI  - Exemplars in the use of technology for management of depression in primary care.
AB  - PURPOSE: Depression care management as part of larger efforts to integrate
      behavioral health care into primary care has been shown to be effective in
      helping patients and primary care clinicians achieve improved outcomes within the
      primary care environment. Central to care management systems is the use of
      registries which enable effective clinic population management. The aim of this
      article is to detail the methods and utility of technology in depression care
      management processes while also highlighting the real-world variations and
      barriers that exist in different clinical environments, namely a federally
      qualified health center and a Veterans Administration clinic. METHODS: We
      analyzed descriptive data from the registries of Access Community Health Centers
      and the William S. Middleton Veterans Administration clinics along with
      historical reviews of their respective care management processes. RESULTS: Both
      registry reviews showed trend data indicating improvement in scores of depression
      and provided baseline data on important system variables, such as the number of
      patients who are not making progress, the percentage of patients who are
      unreachable by phone, and the kind of actions needed to ensure evidence-based and
      efficient care. Both sites also highlighted systemic technical barriers to more
      complete implementation of care management processes. CONCLUSIONS: Care
      management processes are an effective and efficient part of population-based care
      for depression in primary care. Implementation depends on available resources
      including hardware, software, and clinical personnel. Additionally, care
      management processes and technology have evolved over time based on local needs
      and are part of an integrated method to support the work of primary care
      clinicians in providing care for patients with depression.

PMID- 22870557
TI  - An electronic medical record-derived real-time assessment scale for hospital
      readmission in the elderly.
AB  - OBJECTIVE: "Readmission risk score", a 20-point, 4-dimensional tool, is generated
      from the electronic medical record. This study was performed to evaluate the
      ability of the readmission risk score to predict 30-day readmissions among older
      hospitalized patients. METHODS: A retrospective study was conducted utilizing
      data from the electronic medical record. Using a cutoff value of 7, the
      readmission score sensitivity was 61%, specificity was 22%, positive predictive
      value 12%, negative predictive value 77%. The positive and negative likelihood
      ratios were 0.8 and 1.8, respectively. CONCLUSION: The readmission risk score was
      associated with 30-day readmissions (median score of readmitted vs not readmitted
      patients was 8 vs. 5; P = 0.001), and it may be better at identifying those who
      are not at risk for readmission.

PMID- 22870558
TI  - The theory and application of UW ehealth-PHINEX, a clinical electronic health
      record-public health information exchange.
AB  - BACKGROUND: Electronic health records (EHRs) hold the promise of improving
      clinical quality and population health while reducing health care costs. However,
      it is not clear how these goals can be achieved in practice. METHODS: Clinician
      led teams developed EHR data extracts to support chronic disease use cases. EHRs
      were linked with community-level data to describe disease prevalence and health
      care quality at the patient, health care system, and community risk factor
      levels. Software was developed and statistical modeling included multivariate,
      mixed-model, longitudinal, data mining, and geographic information system
      (GIS)/spatial regression approaches. RESULTS: A HIPAA-compliant limited data set
      was created on 192,201 patients seen in University of Wisconsin Family Medicine
      clinics throughout Wisconsin in 2007-2009. It was linked to a commercially
      available database of approximately 6000 variables describing community-level
      risk factors at the census block group. Areas of increased asthma and diabetes
      prevalence have been mapped, identified, and compared to economic hardship.
      CONCLUSIONS: A comprehensive framework has been developed for clinical-public
      health data exchange to develop new evidence and apply it to clinical practice
      and health policy. EHR data at the neighborhood level can be used for future
      population studies and may enhance understanding of community-level patterns of
      illness and care.

PMID- 22870559
TI  - Improving a regional outreach program in a large health system using geographic
      information systems.
AB  - As government-insured populations grow, commercially insured populations
      decrease, and declining insurance reimbursements pressure cost and revenue.
      Health systems must strive to improve quality while lowering costs. Large medical
      centers with rural sites must understand their geography and how distances impede
      access to services, thereby affecting patient health. Without relevant data,
      which can be provided through the use of geographic information systems (GIS)
      technology, improvement is often delayed. Gundersen Lutheran Health System, a
      large multi-specialty system with urban and rural sites in 3 states, is
      developing an evaluative outreach GIS to facilitate understanding of, and
      response to, rural health needs. Investing in GIS technology furthers the health
      system's ability to deliver superior, affordable care.

PMID- 22870560
TI  - Digital ischemia as a paraneoplastic consequence of squamous cell lung carcinoma.
AB  - We report the case of a 40-year-old man who presented with digital ischemia and
      squamous cell lung carcinoma. Based on review of the literature, to our knowledge
      this case represents the youngest patient with lung carcinoma associated with
      digital ischemia and the only one with this type of tumor. The patient's digital
      ischemia symptoms improved rapidly with systemic chemotherapy; however, he did
      eventually lose the distal portion of 1 finger to dry gangrene and mummification.

PMID- 22870561
TI  - Milwaukee health care partnership improves coverage, access, and care
      coordination for underserved.

PMID- 22870562
TI  - MetaStar aids physicians in adoption and use of EHRs for quality improvement.

PMID- 22870563
TI  - Phosphorus additives. A problem for ESRD patients and the public.
AB  - These considerations strongly suggest that a mixed composition of dietary animal
      and plant foods should be encouraged in a diet for patients with CKD, whereas the
      intake of processed foods should be limited. Of course, it is most important to
      restrict intake of phosphorus in all of its forms in the diet of CKD patients

PMID- 22870564
TI  - A cost effective complement to managing the vitamin D deficient and anemic
      dialysis patient in the bundled world.
AB  - Vitamin D deficiency is a common health complication in patients with chronic
      kidney disease and can be treated with an abundance of classical and advanced
      pharmaceutics. However, the impact of bundling in dialysis clinics limits the use
      of the most optimal therapeutics and desired efficacy targets in end-stage renal
      disease patients. To address this issue, we investigated the benefits of adding a
      cost-effective antioxidant and vitamin D nutraceutical (MV-ONE, Nephrian Inc.) to
      patient regiments. This nutraceutical was used in an attempt to replete vitamin D
      levels and decrease inflammation that dialysis patients experience. Additionally,
      we investigated the potential of this therapy to reduce the need for
      erythropoietin-stimulating agents. Results indicate MV-ONE caused: (1) increases
      in 25-OH vitamin D (p = 0.0058), (2) decreases in ESA dose (p = 0.0475), and (3)
      no change in C-reactive protein (p = 0.3290). Overall, this suggests the addition
      of MV-ONE does benefit the vitamin D deficiency and anemia observed in ESRD
      patients.

PMID- 22870565
TI  - 18th annual ranking. Will mandates like expanded QIP knock out the competition?
      Mergers, reorganizations mark 2011-2012 growth.

PMID- 22870566
TI  - Validating a single-question health literacy test among African Americans.

PMID- 22870567
TI  - Need for effective HPV vaccine promotional messaging before sexual activity
      begins.

PMID- 22870568
TI  - Barriers to genetic testing for breast cancer risk among ethnic minority women:
      an exploratory study.
AB  - BACKGROUND/AIMS: To assess awareness of genetic testing for breast cancer risk
      and identify influences on the decision-making process regarding counseling and
      testing among an ethnically-diverse sample of women. METHODS: Semi-structured
      interviews were conducted with 33 women who were breast or ovarian cancer
      survivors or first degree relatives of survivors. Interviews were audiotaped,
      translated, and transcribed. Analysis of transcripts identified relevant themes
      and quotes were extracted for illustration. RESULTS: Low levels of awareness were
      observed in minority women, including those with a significant family history of
      cancer. A number of potential influences on the decision-making process emerged
      including beliefs about risk factors for cancer and opinions about the options
      following testing. Distinct issues were identified within ethnic groups that may
      function as barriers such as concern about the misuse of genetic information
      (African Americans), unfamiliarity with Western preventive medicine (Asians), and
      women prioritizing family obligations over personal health needs (Latinas).
      CONCLUSIONS: Results suggest there may be a need for interventions to raise
      awareness about genetic counseling and testing among minorities. Our findings
      contribute to the literature by using in-depth interviews to uncover potential
      barriers and facilitators to counseling and testing and by including Asians and
      Latinas, groups under-represented in previous research.

PMID- 22870569
TI  - Design and evaluation of a theory-based, culturally relevant outreach model for
      breast and cervical cancer screening for Latina immigrants.
AB  - OBJECTIVES: Breast and cervical cancer are common among Latinas, but screening
      rates among foreign-born Latinas are relatively low. In this article we describe
      the design and implementation of a theory-based (PEN-3) outreach program to
      promote breast and cervical cancer screening to Latina immigrants, and evaluate
      the program's effectiveness. METHODS: We used data from self-administered
      questionnaires completed at six annual outreach events to examine the
      sociodemographic characteristics of attendees and evaluate whether the program
      reached the priority population - foreign-born Latina immigrants with limited
      access to health care and screening services. To evaluate the program's
      effectiveness in connecting women to screening, we examined the proportion and
      characteristics of women who scheduled and attended Pap smear and mammography
      appointments. RESULTS: Among the 782 Latinas who attended the outreach program,
      60% and 83% had not had a Pap smear or mammogram, respectively, in at least a
      year. Overall, 80% scheduled a Pap smear and 78% scheduled a mammogram. Women
      without insurance, who did not know where to get screening and had not been
      screened in the last year were more likely to schedule appointments (P < .05).
      Among women who scheduled appointments, 65% attended their Pap smear and 79%
      attended the mammogram. We did not identify significant differences in
      sociodemographic characteristics associated with appointment attendance.
      CONCLUSIONS: Using a theoretical approach to outreach design and implementation,
      it is possible to reach a substantial number of Latina immigrants and connect
      them to cancer screening services.

PMID- 22870571
TI  - Black Medicaid beneficiaries experience breast cancer treatment delays more
      frequently than whites.
AB  - OBJECTIVE: Delays in treatment initiation may contribute to the poorer breast
      cancer survival among Black women compared with Whites. Lower socioeconomic
      status and lack of access to care are other reasons for the observed disparities.
      We, therefore, examined racial differences in treatment delays for early breast
      cancer in a similarly insured population of Medicaid beneficiaries. DESIGN AND
      SETTING: A retrospective cohort study using linked New Jersey Cancer Registry and
      Medicaid Research files using logistic regression models. PATIENTS: 237 Black and
      485 White women aged 20-64 years diagnosed with early breast cancer between 1997
      and 2001. MAIN OUTCOME MEASURE: Delays in treatment initiation. RESULTS: Blacks
      experience adjuvant chemotherapy delays more often than Whites. Black women had
      two-fold odds (95% confidence interval, 1.04, 4.38) of > or = 3 months delay in
      adjuvant chemotherapy than Whites. Blacks were also more likely to experience
      radiation treatment delays but this finding was not statistically significant
      (odds ratio 1.72, 95% CI .79, 3.77). No racial differences were observed for
      surgical and hormonal treatment delays. CONCLUSION: Blacks experienced delays in
      initiating adjuvant chemotherapy more frequently than Whites. These differences
      were observed even in a population with similar socioeconomic status and
      insurance access, suggesting that cultural and psychosocial factors may
      contribute to the observed differences.

PMID- 22870570
TI  - Cholesterol, lipoproteins, and breast cancer risk in African American women.
AB  - BACKGROUND: Lipid levels, including high-density lipoprotein cholesterol (HDL-C),
      low-density lipoprotein cholesterol (LDL-C), and triglycerides, have been
      reported to be associated with breast cancer risk. METHODS: We studied African
      American women (97 breast cancer cases and 102 controls) accrued through a
      population-based, case-control study in the Washington, DC metropolitan area
      during 1997 and 1998. Plasma lipid levels were measured using enzymatic methods.
      Logistic regressions (adjusted for age, age at menarche, parity, previous alcohol
      consumption, and education) were used to explore the associations between lipid
      levels and breast cancer. RESULTS: Through multivariable-adjusted regression, we
      observed a significant inverse association between breast cancer risk and
      increasing levels of total cholesterol (OR=.46, 95% Cl = .25-.85) and LDL (OR =
      .41, 95% CI = .21-.81), whereas lower levels of HDL were associated with a
      significant increase in risk (OR = 1.99, 95% CI = 1.06-3.74). CONCLUSIONS: Our
      data demonstrate significant reductions in breast cancer risk with high levels of
      total cholesterol and significant increase in risk when HDL levels are low. These
      data are in support of a protective effect of cholesterol which has been reported
      in other populations; further, these findings add to the literature in an
      understudied population, African American women.

PMID- 22870572
TI  - Racial/ethnic differences in upper-tract urothelial cancer.
AB  - OBJECTIVES: Information on clinical characteristics, pattern of initial treatment
      and survival in patient with upper-tract urothelial carcinomas (UTUC) is scarce.
      Our study examined the racial/ethnic differences in patients diagnosed with
      incident UTUC. DESIGN: Observational study. The data analyses included:
      proportion and ANOVA for categorical and continuous variables, respectively;
      Kaplan-Meier method for calculating overall survival; and Cox-proportional
      hazards models for obtaining adjusted hazard-ratios. SETTING: Regions of the
      Surveillance, Epidemiology and End Results (SEER). PATIENTS OR PARTICIPANTS:
      16,702 incident UTUC patients identified from the SEER dataset 1988-2007 (14,192
      White, 967 Hispanic, 718 African American and 825 Asian). INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: Race/ethnicity-specific distributions of demographics,
      tumor characteristics, patterns of initial treatment, and survival. RESULTS:
      African American and Hispanic patients were diagnosed at a younger age than
      Whites and Asians (P = .001). Hispanics were more likely to be diagnosed with
      larger tumor size than Whites and Asians (P < .0001). Asians were more likely to
      be diagnosed with advanced stage and higher tumor grade. Cox-regression revealed
      that Whites and Asians were significantly less likely to die after UTUC diagnosis
      than African Americans (HR = .78, 95% Cl = .67-.91 and HR = .75, 95% CI = .61
      .91, respectively; all P = < .01). CONCLUSIONS: Our study found that Asians had
      worse tumor characteristics at the initial presentation than the other groups in
      this study, but that their risk of dying was lower. Further research is needed to
      include a larger number of Asian patients to examine subgroup differences and to
      confirm the paradoxical finding of higher survival with poor clinical
      characteristics.

PMID- 22870573
TI  - Health-related quality of life in elderly black and white patients with cancer:
      results from Medicare managed care population.
AB  - OBJECTIVE: To compare differences in various aspects of health-related quality of
      life (HRQOL) between Black and White individuals diagnosed with cancer. DESIGN:
      The data were extracted from 2005-2007 Medicare Health Outcome Survey, a health
      outcomes measure for the Medicare population in managed care settings. A total of
      14089 Black and White respondents aged > or = 65 with cancer were included in the
      study. Multivariable linear regressions were used to assess the association
      between race and the HRQOL after accounting for age, sex, education years,
      marital status, and non-cancer comorbid conditions. RESULTS: When compared with
      their White counterparts, Black patients had lower scores for the physical
      component summary (PCS) and mental component summary (MCS), and all health
      domains with the exception of vitality. After adjusting for demographic features
      and comorbid conditions, the MCS scores of Black patients were still lower than
      that of White patients. However, the mean PCS was not different for Black and
      White patients. Black patients had significantly lower HRQOL in general health,
      social functioning, and role emotion, whereas they had a higher mean score in
      vitality. CONCLUSIONS: Race had a significant impact on quality of life for older
      cancer patients. The effect was likely to be moderated by comorbid conditions and
      socioeconomic indicators. To optimize cancer outcomes at the population level, it
      is important to identify subgroups of cancer patients with an increased risk of
      low quality of life and to develop appropriate supportive interventions of cancer
      care.

PMID- 22870574
TI  - Racial disparities in the risk of developing obesity-related diseases: a cross
      sectional study.
AB  - OBJECTIVES: Analyze racial/ethnic disparities in the prevalence of obesity and
      its related diseases in Massachusetts and assess disparities in the risk of
      developing diseases related to overweight and obesity. DESIGN: Cross-sectional
      analysis of survey data. SETTING: Community-based US population. SUBJECTS: 63,235
      non-institutionalized adults in Massachusetts. MAIN OUTCOME MEASURES: BMI,
      overweight and obesity prevalence and prevalence of obesity-related- diseases,
      odds of developing obesity-related diseases. Participants were considered
      hypercholesterolemic, diabetic, hypertensive, or having a cardiovascular disease
      if they reported that a health professional told them that they had such a
      disease. Behavioral characteristics of respondents included fruit and vegetable
      consumption, alcohol drinking, smoking, and physical activity. Demographic
      variables included sex, age, marital status, employment status, household income,
      region of residence, and educational status. RESULTS: Blacks (OR = 1.97) and
      Hispanics (OR = 1.81) had higher odds of obesity as compared to Whites. Blacks
      had higher odds of high blood pressure (OR = 1.88), heart attack (OR = 1.40) and
      stroke (OR = 2.14) than Whites. Hispanics were more likely to have high blood
      pressure (OR = 1.34), high cholesterol (OR = 1.56), stroke (OR = 1.71), and heart
      attack (OR = 1.54) than Whites. Hispanics (OR = 2.71) and Blacks (OR = 2.58) had
      the highest odds of diabetes. CONCLUSIONS: Minority groups share a
      disproportionate risk of obesity and obesity-related diseases. Hispanics and
      Blacks have significantly higher odds of obesity and its related diseases.
      Continued emphasis on racial/ethnic groups at greatest risk of obesity remains
      critical.

PMID- 22870575
TI  - Race, ethnicity, and the relevance of obesity for social integration.
AB  - OBJECTIVE: To examine race and ethnic differences in the importance of obesity
      for social integration using the National Longitudinal Study of Adolescent Health
      (Add Health). DESIGN: A cross-sectional study utilizing survey-adjusted
      statistics and multivariate logistic and linear regression models. Models were
      stratified by sex and included interaction terms capturing race, ethnicity and
      obesity. SETTING: United States of America. PARTICIPANTS: A nationally
      representative sample of 15,355 respondents grades 7 through 12 who participated
      in both the In-School and In-Home Wave I surveys of Add Health. MAIN OUTCOME
      MEASURES: Four self-reported and schoolmate-reported indicators of social
      integration. RESULTS: The consequences of obesity for social integration are
      greatest for White adolescents, who were selected by almost 2 fewer schoolmates
      as friends and had half the odds of having their friendships reciprocated
      compared with non-obese White adolescents. The social disadvantage of obesity was
      lower for non-White adolescents; though they are selected by significantly fewer
      schoolmates as friends and were less likely to have their friendships
      reciprocated, they did not face additional discrimination from being both obese
      and minority. CONCLUSIONS: There are significant differences between obese and
      non-obese adolescents by race and ethnicity in friendships. As friendships are
      among the most valued assets in adolescence, understanding the impact of obesity
      on access to friendships for diverse adolescents is a necessary component to
      understanding the complex motivations that guide health-related behavior at these
      formative ages.

PMID- 22870576
TI  - Association of an aldehyde dehydrogenase 2 (ALDH2) gene polymorphism with hyper
      low-density lipoprotein cholesterolemia in a Japanese population.
AB  - OBJECTIVE: The relationship among alcohol metabolism, lipid profile and
      cardiovascular disease has been a matter of concern, and aldehyde dehydrogenase-2
      (ALDH2) is one of the key enzymes involved in alcohol metabolism. The frequency
      of ALDH2 gene G/A polymorphism (with the substitution of glutamic acid to lysine)
      varies widely among ethnic groups; the polymorphism is prevalent among Asian
      people but rare in other ethnic groups. The objective of our study was to
      investigate the association between the ALDH2 gene G/A polymorphism and lipid
      profile, including the low-density lipoprotein cholesterol (LDL-C) status, in a
      general Japanese population with no or light-to-moderate alcohol drinking habits.
      METHODS: Anthropometric and biochemical variables including lipid- and glucose
      related factors were measured in a total of 383 Japanese participants (170 males
      and 213 females; mean age, 45 +/- 8.6 years), free of cardiovascular disease. All
      participants were genotyped by an allele-specific DNA assay. RESULTS: The numbers
      of participants with the G/ G, G/A and A/A genotypes were 213, 139 and 31,
      respectively. The percentages of hyper-LDL-cholesterolemia (identified by LDL-C >
      or = 3.63 mmol/L) were 31.9%, 45.3% and 29.0% in participants with the G/G, G/A
      and A/A genotypes, respectively. Carrying the G/A + AA genotype was a significant
      and positive factor related to hyper-LDL-cholesterolemia with an odds ratio of
      1.62 (95% CI: 1.04-2.52) after adjusting for the other variables including
      drinking status. CONCLUSION: Our findings suggest that the ALDH2 gene G/A
      polymorphism can affect the lipid profile such as LDL-C status in this
      population. The association between the polymorphism and LDL-C status warrants
      further investigation.

PMID- 22870577
TI  - The correlation between serum amyloid A and reactive oxygen metabolites in a
      young Mongolian population.
AB  - OBJECTIVE: Chronic inflammation and oxidative stress are associated with
      lifestyle-related diseases. Research into the pathophysiology of lifestyle
      related diseases is important for Mongolian people. Our study investigated the
      correlation among the d-ROMs test (a measure of the total oxidant capacity of
      blood), serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP)
      levels in a young Mongolian population. METHODS: The data, including
      anthropometric and biochemical markers, were collected from 78 Mongolian
      volunteers (male/female = 27/ 51, mean age 21 years). The correlation between the
      SAA and d-ROMs levels was examined, as well as the correlation between the hs-CRP
      and d-ROMs levels. RESULTS: The SAA levels were 3.2 microg/mL (median), hs-CRP
      .04 mg/dL (median) and d-ROMs 309 CARR U, respectively. There was a significant
      and positive correlation between the SAA and d-ROMs levels (r=.40, P<.01), in
      addition to a significant and positive correlation between the hs-CRP and d-ROMs
      levels (r = .32, P < .01). These significant correlations remained independent in
      a multiple linear regression analysis. A subgroup analysis by sex revealed the
      positive correlation between the SAA and d-ROMs levels to be greater, relative to
      that between the hs-CRP and d-ROMs levels, particularly in the female group.
      CONCLUSIONS: The coexistence of chronic inflammation and oxidative stress can be
      present even in young Mongolian people, suggesting that their coexistence may be
      a target of early prevention of lifestyle-related diseases. In addition, not only
      hs-CRP, but also SAA can be used to evaluate the relationship of oxidative stress
      in this population. Further studies are necessary to confirm the observed
      relationship.

PMID- 22870578
TI  - Prevalence and correlates of hypertension among the Ibibio/Annangs, Efiks and
      Obolos: a cross sectional community survey in rural South-South Nigeria.
AB  - OBJECTIVE: The objective of the study was to assess the public health burden of
      hypertension in the rural communities in southeastern Nigeria (Niger Delta region
      of Nigeria). DESIGN/SETTING: The study was a cross-sectional study in three rural
      communities in the Cross River and Akwa Ibom States of Nigeria. Demographic,
      anthropometric information, prior history of hypertension or stroke in each
      participant or their parents was obtained with a questionnaire. Height, weight,
      systolic blood pressure (SBP), and diastolic blood pressure (DBP) of respondents
      were measured by standard methods, and body mass index calculated. RESULT: The N
      of respondents was 3869; 1608 (41.6%) males, 2261 (58.4%) females; 1120 (29.0%)
      Efiks, 1877 (48.5%) Ibibio/Annangs, and 872 (22.5%) Obolos. Mean SBP and DBP were
      significantly higher in males than in females (P < .001). Prior awareness of
      hypertension was 2.8%. The overall prevalence of hypertension was 914 (23.6%);
      31.2% males and 18.1% females (P < .001). The prevalence of hypertension in the
      ethnic groups was 479 (25.5%) among Ibibio/Annangs; 287 (25.6%) among the Efiks
      and 130 (14.9%) among the Obolos. Prehypertension occurred in 17.2% of total
      population, 17.5% males and 16.9% females (P = .66). CONCLUSION: Hypertension is
      already a major public health burden in rural communities of these two states,
      despite a very low incidence of obesity and cigarette smoking.

PMID- 22870579
TI  - Prevalence of hypertension in Kegbara-Dere, a rural community in the Niger Delta
      region, Nigeria.
AB  - OBJECTIVES: Hypertension has become a major health burden in sub-Saharan Africa,
      mainly due to urbanization and Western acculturation. We investigated the
      prevalence of hypertension and risk factors in a rural community in South-South
      Nigeria. DESIGN, SETTING, PARTICIPANTS: Blood pressure and anthropometric indices
      were measured during a cross-sectional study of community health status among
      1078 adults, aged > or = 18 years, in 2008. Information on lifestyle was also
      collected through structured interviews. STATISTICS: Unadjusted hypertension
      prevalence was calculated against selected risk factors, and association was
      demonstrated using risk ratios with 95% confidence intervals. Chi-square was used
      to test for statistical significance at P < .05. Adjusted analysis was done for
      age by direct standardization using a reference population. MAIN OUTCOME MEASURE:
      Prevalence of hypertension, defined as systolic and diastolic blood pressure > or
      = 140 mm Hg and > or = 90 mm Hg respectively and/or current use of
      antihypertensive medication. RESULTS: Crude prevalence of hypertension was 18.3%
      (95% CI = 16.0-20.7), while the age-adjusted prevalence was 2.63% (95% Cl = 2.59
      2.66). Hypertension rate increased with age (RRs > 2.0, P = .00) and was higher
      in those married (RR = .35, P = .00), but showed no sex difference (RR = 1.13, P
      = .34). Hypertension was associated with tobacco chewing/ snuffing (RR = 2.32, P
      = .05) and history of diabetes (RR = 3.36, P = .00); but central obesity, alcohol
      intake, cigarette smoking, and family history of hypertension or diabetes showed
      no valid association. CONCLUSIONS: The study found a high prevalence of
      hypertension in a rural community. Although, the influence of selected risk
      factors could not be established, screening and health promotion in rural areas
      should be intensified.

PMID- 22870580
TI  - Prevalence of hypertension and diabetes mellitus in adults from a rural community
      in Ghana.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of hypertension
      and diabetes mellitus (DM) in the Adankwame community of Ghana. DESIGN: This was
      a cross-sectional, observational study. SETTING: This study took place in the
      rural Adankwame community of Ghana, approximately 12 km from Kumasi, Ghana.
      PARTICIPANTS: Study subjects were adults (older than aged 18 years). A two-tier
      random sampling approach was taken to recruit study participants to achieve a
      sample size of 326 adults, 94 males and 232 females. MAIN OUTCOME MEASURES: The
      subjects' height, weight, abdominal circumference, demographic and risk factor
      information, blood pressure measurements, and blood glucose levels were measured
      and recorded. RESULTS: The mean systolic and diastolic blood pressures in the
      population were 131 (SD 26.61) and 78 mmHg (SD 15.24), respectively. The
      prevalence of hypertension was 0.35 (95% CI 0.30-0.40). The prevalence of pre
      hypertension, Stage 1 hypertension, and Stage 2 hypertension were approximately
      0.248, 0.19, and 0.16, respectively. Mean fasting blood sugar and random blood
      sugar in the study population were 108 mg/dL (SD 35.33) and 131 mg/dL (SD 41.35),
      respectively. The overall prevalence of DM in this sample population was 0.077
      (95% Cl 0.05-0.11). CONCLUSIONS: Hypertension and diabetes mellitus are rising as
      diseases of public health importance in the Adankwame community. Research to
      provide substantial data on the prevalence of these two diseases in Ghana is
      needed to inform national non-communicable disease policy.

PMID- 22870581
TI  - Racial discrimination and health in Brazil: evidence from a population-based
      survey.
AB  - OBJECTIVE: To investigate the association between racial discrimination and three
      health outcomes: self-rated health (SRH), physical morbidity and depression, in
      the Brazilian population. DESIGN: Cross-sectional study based on data obtained
      from a representative national survey carried out in 2008: The Research for
      Social Dimension of Inequalities. PARTICIPANTS: 3,863 household heads who
      classified themselves as Blacks or Mullatoes regarding their race and answered
      the entire research questionnaire. MAIN OUTCOME MEASURES: Racial discrimination
      was measured through a scale of 9 domains based on a previously validated
      instrument and classified into two categories: no discrimination and any
      experience of racial discrimination. SRH was based on the question from the SF-36
      quality of life instrument. Physical morbidity and depression were obtained from
      a list of chronic diseases from the questionnaire. Regression analysis was
      carried out for the three health outcomes controlling for socioeconomic,
      demographic, health behavior variables, and body mass index. RESULTS: Racial
      discrimination was negatively associated with health for all evaluated outcomes.
      Any experience of racial discrimination was associated with 1.37 more chance of
      having worse SRH, 1.55 more chance of having more physical morbidities and 1.77
      more chance of having depression, even after controlling for confounders.
      CONCLUSION: An impact of racial discrimination on the health of the Brazilian
      population was found, regardless of the health indicator used, which revealed
      that depression was the health outcome with the most pronounced association.

PMID- 22870582
TI  - Effects of parity on blood pressure among West African Dogon women.
AB  - OBJECTIVE: This study examined the effect of parity on blood pressure (BP)
      readings and BMI among rural West African Dogon women. DESIGN: Correlational
      research design. SETTING: Sangha, West Africa PARTICIPANTS: 133 West African
      Dogon Women METHODS: Demographic survey including age, number of children,
      history of hypertension, and village affiliation. BP readings were taken in
      accordance with JNC-7 guidelines. BMI was calculated from height and weight.
      RESULTS: Women with BP readings diagnostic of hypertension were typically older
      (M = 55.72 years) than those who were normotensive (M = 42.40). However, BMI, on
      average, was within normal range for both groups (22.81 and 22.15, respectively).
      A statistically significant difference was found between number of children and
      systolic BP (SBP), P = .015, with those having 5 or more children with higher SBP
      than those with one to three children. A statistically significant difference, P
      = .001, was found between hypertension and normotensive diagnostic groups.
      CONCLUSIONS: This study shows that increased parity of five or more children may
      contribute to West African Dogon women's risk factors for hypertension in terms
      of increased SBP. Because BMI was within normal range for both groups of women,
      it was not shown to be an independent risk factor for hypertension in this
      sample. Further studies, with larger samples followed throughout their
      childbearing years (before, during, and after each pregnancy), are needed before
      more definitive conclusions can be made regarding the effects of parity on BMI
      and BP among rural West African Dogon women.

PMID- 22870583
TI  - Review of the scientific literature on the health of the Roma and Sinti in Italy.
AB  - BACKGROUND: Roma and Sinti in Italy are excluded from the rest of society, often
      live in precarious housing conditions and have poor access to health services. In
      Italy, the Roma and Sinti minority (.3% of the overall population) is scarcely
      represented if compared with other European countries. METHODS: To establish what
      is known and how Roma and Sinti health is studied in Italy, we conducted a review
      of the scientific literature, including articles published between 2000 and 2010,
      found in Medline, Embase and Web of Science. RESULTS: We analyzed 15 relevant
      articles out of 32 references. Four papers describe rare autosomal recessive
      disorders. Four illustrate outbreaks of measles. The remaining papers describe
      health conditions suffered by this minority. All but two, however, are based on
      data collected at health services. CONCLUSIONS: The lack of prevalence data and
      analysis of determinants is a detriment to the health of the Roma and Sinti
      populations in Italy. Participatory research and evidence-based interventions are
      needed to improve health outcomes and living conditions of the Roma and Sinti
      people.

PMID- 22870584
TI  - Differences in conventional cardiovascular risk factors in two ethnic groups in
      India.
AB  - BACKGROUND: Studies have been carried out at national and international levels to
      assess ethnic variations in the prevalence of cardiovascular diseases and their
      risk factors. However, ethnic variations in the contribution of various risk
      factors to complex diseases have been scarcely studied. OBJECTIVES: Our study
      examined such variations in two ethnic groups in India, namely, Meiteis of
      Manipur (northeast India) and Aggarwals of Delhi (north India). METHODS: Through
      random sampling, we selected 635 participants from the Meitei community and 181
      Aggarwals from the Aggarwal Dharmarth Hospital, Delhi. Patients with coronary
      artery disease (CAD) and hypertension were identified based on their recent
      medical diagnostic history. Anthropometric parameters such as height, weight,
      waist and hip circumferences along with physiological parameters (blood
      pressures, both systolic and diastolic) and biochemical parameter (lipid profile)
      were measured for all study participants. Patient parameters were available from
      the medical reports recorded when patients were first diagnosed. RESULTS: Among
      CAD individuals, the Aggarwals showed higher mean values of weight, body mass
      index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total
      cholesterol (TC), triglyceride (TC), low density lipoprotein (LDL), and very low
      density lipoprotein (VLDL) but had lower high density lipoprotein (HDL) levels
      than the Meiteis. The same trend for weight, BMI and lipid parameters could be
      seen among hypertensive individuals. In step-wise regression analysis, SBP, LDL
      and TG were found to significantly contribute to the risk for CAD in the
      Aggarwals; whereas in the Meiteis, SBP, VLDL, HDL, TC and LDL were found to
      significantly contribute to the risk for CAD. In hypertensive Aggarwal
      participants, SBP, DBP and waist-to-hip ratio were significant contributors for
      hypertension; whereas SBP, DBP, and height contributed significantly to risk for
      hypertension among the Meiteis. CONCLUSION: We found marked differences in
      conventional risk factors between the two ethnic groups. In India, as found
      elsewhere, the presence of substructuring of groups and hence, genetic isolation
      is high. More research is needed within this context to unveil the conventional
      risk factors for complex diseases.

PMID- 22870585
TI  - Advances in hemoglobinopathy detection and identification.
AB  - Hemoglobin disorders consist of two different groups, the structural hemoglobin
      variants and the thalassemias. The structural hemoglobin variants typically are
      based on the point mutations in the alpha- or beta-globin chain that results in a
      single-amino acid substitution in the corresponding globin chain, whereas
      thalassemias are caused by quantitative reduction in globin chain synthesis.
      Various techniques are applied for the laboratory investigation of these
      diseases, among them mass spectrometry (MS) for the detection and identification
      of structural hemoglobin variants and array techniques for the thalassemias. In
      this review, we present in the first part the most important mass spectrometric
      techniques applied in hemoglobin variant detection and identification and discuss
      several important aspects of this analysis technique in hematology. In the second
      part, the DNA analysis techniques used in hemoglobin analysis, such as reverse
      hybridization or microarray-based comparative genomic hybridization (CGH)
      techniques, are briefly discussed.

PMID- 22870586
TI  - Biomarkers in hemodialysis patients.
AB  - Patients with chronic kidney disease (CKD) are, compared to the general
      population, at higher risk of cardiovascular disease (CVD), including sudden
      death, coronary artery disease (CAD), congestive heart failure (HF), stroke, and
      peripheral artery disease. The presence of CVD is independently associated with
      kidney function decline. Renal insufficiency is a strong and independent
      predictor of mortality in patients with different CKD stages. The interplay of
      traditional and nontraditional risk factors is complex such that risk factor
      profiles are different in CKD patients. Seemingly, paradoxical associations
      between traditional risk factors and cardiovascular outcome complicate efforts to
      identify real cardiovascular etiology in these patients. Additional tools are
      often required to aid clinical assessment of cardiovascular risk. Recently, a
      number of cardiovascular biomarkers were identified as predictors of outcome in
      CVD. These may be used to guide early diagnosis and therapy for CVD or may
      predict outcome in CKD. This review focuses on the potential diagnostic and
      prognostic use of some important new biomarkers including brain natriuretic
      peptide (BNP), cardiac troponins (cTns), inflammatory markers, adhesion
      molecules, and asymmetric dimethylarginine (ADMA) in CKD as well as those
      patients with end-stage renal failure.

PMID- 22870587
TI  - Cytokines and cytokine-specific therapy in asthma.
AB  - Asthma is increasing in prevalence worldwide. It is characterized by typical
      symptoms and variable airway obstruction punctuated with episodes of worsening
      symptoms known as exacerbations. Underlying this clinical expression of disease
      is airway inflammation and remodeling. Cytokines and their networks are
      implicated in the innate and adaptive immune responses driving airway
      inflammation in asthma and are modulated by host-environment interactions. Asthma
      is a complex heterogeneous disease, and the paradigm of Th2 cytokine-mediated
      eosinophilic inflammation as a consequence of allergic sensitization has been
      challenged and probably represents a subgroup of asthma. Indeed, as attention has
      switched to the importance of severe asthma, which represents the highest burden
      both to the patient and health care provider, there is an increasing recognition
      of inflammatory subphenotypes that are likely to be driven by different cytokine
      networks. Interestingly, these networks may be specific to aspects of clinical
      expression as well as inflammatory cell profiles and therefore present novel
      phenotype-specific therapeutic strategies. Here, we review the breadth of
      cytokines implicated in the pathogenesis of asthma and focus upon the outcomes of
      early clinical trials conducted using cytokines or cytokine-blocking therapies.

PMID- 22870588
TI  - Somatic mitochondrial DNA mutations in human cancers.
AB  - Mitochondria are ubiquitous organelles in eukaryotic cells principally
      responsible for regulating cellular energy metabolism, free radical production,
      and the execution of apoptotic pathways. Abnormal oxidative phosphorylation
      (OXPHOS) and aerobic metabolism as a result of mitochondrial dysfunction have
      long been hypothesized to be involved in tumorigenesis. In the past decades,
      numerous somatic mutations in both the coding and control regions of
      mitochondrial DNA (mtDNA) have been extensively examined in a broad range of
      primary human cancers, underscoring that accumulation of mtDNA alterations may be
      a critical factor in eliciting persistent mitochondrial defects and consequently
      contributing to cancer initiation and progression. However, the roles of these
      mtDNA mutations in the carcinogenic process remain largely unknown. This review
      outlines a wide variety of somatic mtDNA mutations identified in common human
      malignancies and highlights recent advances in understanding the causal roles of
      mtDNA variations in neoplastic transformation and tumor progression. In addition,
      it briefly illustrates how mtDNA alterations activate mitochondria-to-nucleus
      retrograde signaling so as to modulate the expression of relevant nuclear genes
      or induce epigenetic changes and promote malignant phenotypes in cancer cells.
      The present state of our knowledge regarding how mutational changes in the
      mitochondrial genome could be used as a diagnostic biomarker for early detection
      of cancer and as a potential target in the development of new therapeutic
      approaches is also discussed. These findings strongly indicate that mtDNA
      mutations exert a crucial role in the pathogenic mechanisms of tumor development,
      but continued investigations are definitely required to further elucidate the
      functional significance of specific mtDNA mutations in the etiology of human
      cancers.

PMID- 22870589
TI  - Biochemical and genetic markers of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a very common pathology, affecting over 150 million
      men worldwide. The pathogenesis is typically multifactorial, involving a
      kaleidoscope of organic, endocrine, and psychogenic factors. In general, ED is
      divided into organic and psychogenic impotence, but most men with organic
      etiologies have an associated psychogenic component. Given the high frequency of
      this pathology, the identification of biochemical and genetic correlates and/or
      markers is of pivotal interest not only for treating preciously these patients
      and preventing serious psychological consequences but also for the high risk for
      occult cardiovascular disease (CVD) that often accompanies or follows this
      pathology. A variety of cardiovascular risk factors have been associated with
      both the onset and the severity of ED, including markers of endothelial function,
      thrombosis, and especially dyslipidemia, so that their measurement should now be
      considered as an important part of the increased global cardiometabolic risk
      profile in patients with ED. While nitric oxide (NO), asymmetric dimethylarginine
      (ADMA), and endothelin (ET) hold some promises as biochemical markers of both CVD
      and ED, there are several technical and clinical drawbacks that make their
      measurement overall meaningless in the clinical practice. As regards genetic
      polymorphisms, controversial results have been provided so far. Although some
      genetic markers were consistently associated with ED, other studies failed to
      demonstrate significant associations, highlighting a substantial bias in
      standardization of methodologies and patient enrolment. Nevertheless, further
      research in this area should be encouraged, since the first promising evidence
      that gene therapy might be effective to restore the decline in ED has been
      provided in the animal model.

PMID- 22870590
TI  - Asbestos-related disease: screening and diagnosis.
AB  - Malignant pleural mesothelioma (MPM) is an extremely aggressive tumor which
      develops in the epithelial lining of the lungs. Exposure to asbestos is the most
      influential risk factor for developing this disease. Despite recent advances in
      the treatment of other types of cancer, patients with mesothelioma currently face
      a poor prognosis. Therefore, it is highly important to develop an early
      diagnostic method with the greatest challenge on screening techniques to detect
      the disease at a subclinical stage. Early detection is critical for the
      development of more effective therapies in these patients. Unfortunately,
      radiologic studies have not proven effective. Biomarkers might be a useful
      adjunct tool among populations previously exposed to asbestos. This review will
      provide an update of recent progress in serum biomarkers (osteopontin (OPN),
      soluble mesothelin (SM), and megakaryocyte potentiating factor (MPF)) to
      diagnose, detect, and monitor MPM. Of these, SM has demonstrated the greatest
      diagnostic potential although MPF may serve as an equal alternative. Despite
      recent studies, it is apparent that long-term large-cohort research is required
      to conclusively demonstrate the usefulness of these markers in this disease.

PMID- 22870591
TI  - Biochemistry of envenomation.
AB  - Venoms and toxins are of significant interest due to their ability to cause a
      wide range of pathophysiological conditions that can potentially result in death.
      Despite their wide distribution among plants and animals, the biochemical
      pathways associated with these pathogenic agents remain largely unexplored.
      Impoverished and underdeveloped regions appear especially susceptible to
      increased incidence and severity due to poor socioeconomic conditions and lack of
      appropriate medical treatment infrastructure. To facilitate better management and
      treatment of envenomation victims, it is essential that the biochemical
      mechanisms of their action be elucidated. This review aims to characterize
      downstream envenomation mechanisms by addressing the major neuro-, cardio-, and
      hemotoxins as well as ion-channel toxins. Because of their use in folk and
      traditional medicine, the biochemistry behind venom therapy and possible
      implications on conventional medicine will also be addressed.

PMID- 22870592
TI  - Induced pluripotent stem cells in research and therapy.
AB  - Induced pluripotent stem cells (iPSC) are derived from human somatic cells
      through ectopic expression of transcription factors. This landmark discovery has
      been considered as a major development towards patient-specific iPSC for various
      biomedical applications. Unlimited self renewal capacity, pluripotency and ease
      of accessibility to donor tissues contribute to the versatility of iPSC. The
      therapeutic potential of iPSC in regenerative medicine, cell-based therapy,
      disease modelling and drug discovery is indeed very promising. Continuous
      progress in iPSC technology provides clearer understanding of disease
      pathogenesis and ultimately new optimism in developing treatment or cure for
      human diseases.

PMID- 22870593
TI  - Role of immunohistochemical cyclo-oxygenase-2 (COX-2) and osteocalcin in
      differentiating between osteoblastomas and osteosarcomas.
AB  - BACKGROUND/AIMS: Differential diagnosis between aggressive osteoblastoma and low
      grade osteosarcoma may be very difficult or even impossible on a small biopsy.
      This study was designed to assess the usefulness of immunoexpression of COX-2 and
      osteocalcin in the differential diagnosis of the two tumour types. METHODS:
      Immunostaining of COX 2 and osteocalcin were studied in 9 osteoblastomas and 30
      osteosarcomas. RESULTS: All osteoblastomas and 11/20 (55%) high-grade
      osteosarcomas showed COX-2 immunoreactivity. All low grade osteosarcomas were COX
      2 negative. COX-2 was significantly higher (p<0.002) in osteoblastomas 9/9 (100%)
      than in osteosarcomas 13/30 (43%) and in aggressive osteoblastomas versus low
      grade osteosarcomas (p<0.01). Osteocalcin was found in tumour cells of all
      osteosarcomas and osteoblastomas and in the osteoid matrix of 84% of
      osteosarcomas and 78% of osteoblastomas. Strong osteocalcin was significantly
      higher (p<0.02) in osteoblastomas (78%) than in osteosarcomas (27%). CONCLUSION:
      COX-2 is a valuable marker in distinction between osteosarcoma and osteoblastoma.
      Negative COX-2 could confirm the diagnosis of low grade osteosarcoma versus
      aggressive osteoblastoma. Intensity and distribution of osteocalcin may indicate
      the degree of osteoblastic differentiation.

PMID- 22870594
TI  - CD133 marks for colorectal adenocarcinoma.
AB  - CD133, a marker which has been advocated to mark colorectal carcinoma "stem or
      tumour initiating cells" is amongst the frequently studied markers in colorectal
      cancer. A study was conducted at the Department of Pathology, University of
      Malaya Medical Centre to determine the expression of CD133 in 56 archived,
      formalin-fixed, paraffin-embedded colorectal adenocarcinoma in comparison with
      adjacent benign colorectal epithelium by immunohistochemical staining for CD133
      expression. CD133 immunopositivity was determined as staining at the glandular
      luminal surface or in the intraluminal debris. Expression was semiquantitated for
      (1) proportion of CD133 immunopositivity in the malignant or adjacent benign
      colorectal epithelium and (2) intensity of staining. The final score of CD133
      immunopositivity was arbitrarily taken as proportion of CD133 immunopositivity
      multiplied by intensity of staining in both the malignant and adjacent benign
      colorectal epithelium. CD133 expression was observed in significantly increased
      frequency in 49 (87.5%) colorectal adenocarcinoma compared with 15 (26.8%) of the
      adjacent benign colorectal epithelium (p<0.05). In terms of immunopositivity
      score (proportion of CD133 immunopositivity multiplied by intensity of staining),
      colorectal adenocarcinoma had a mean arbitrary score of 8.5 which was
      significantly higher than the mean immunopositivity score of 0.5 of the adjacent
      benign colorectal epithelium (p<0.05). In addition, the maximum immunopositivity
      score for the adjacent benign colorectal epithelium was 4, while 38 (67.9%) of
      colorectal adenocarcinoma had scores >4. This study shows that CD133 is able to
      mark colorectal adenocarcinoma but it is still unclear at this juncture whether
      CD133 is indeed a marker for colorectal adenocarcinoma "stem cells".

PMID- 22870595
TI  - Variant of Helicobacter pylori CagA proteins induce different magnitude of
      morphological changes in gastric epithelial cells.
AB  - Infection with Helicobacter pylori cagA-positive strains is associated with
      gastroduodenal diseases. The CagA protein is injected into gastric epithelial
      cells and supposedly induces morphological changes termed the 'hummingbird
      phenotype', which is associated with scattering and increased cell motility. The
      molecular mechanisms leading to the CagA-dependent morphological changes are only
      partially known. The present study was carried out to investigate the effect of
      CagA variants on the magnitude of gastric epithelial cell morphological changes.
      Recombinant 3' terminal domains of cagA were cloned and expressed in a gastric
      epithelial cell line and the hummingbird phenotype was quantified by microscopy.
      The 3' region of the cagA gene of Malaysian H. pylori isolates showed six sub
      genotypes that differed in the structural organization of the EPIYA repeat
      sequences. The percentage of hummingbird cells induced by CagA increased with
      duration of transfection. The hummingbird phenotype was observed to be more
      pronounced when CagA with 4 EPIYA motifs rather than 3 or 2 EPIYA motifs was
      produced. The activity of different CagA variants in the induction of the
      hummingbird phenotype in gastric epithelial cells depends at least in part on
      EPIYA motif variability. The difference in CagA genotypes might influence the
      potential of individual CagAs to cause morphological changes in host cells.
      Depending on the relative exposure of cells to CagA genotypes, this may
      contribute to the various disease outcomes caused by H. pylori infection in
      different individuals.

PMID- 22870596
TI  - The discrimination of d-tartrate positive and d-tartrate negative S. enterica
      subsp. enterica serovar Paratyphi B isolated in Malaysia by phenotypic and
      genotypic methods.
AB  - Serotyping is not sufficient to differentiate between Salmonella species that
      cause paratyphoid fever from the strains that cause milder gastroenteritis as
      these organisms share the same serotype Salmonella Paratyphi B (S. Paratyphi B).
      Strains causing paratyphoid fever do not ferment d-tartrate and this key feature
      was used in this study to determine the prevalence of these strains among the
      collection of S. Paratyphi B strains isolated from patients in Malaysia. A total
      of 105 isolates of S. Paratyphi B were discriminated into d-tartrate positive
      (dT+) and d-tartrate negative (dT) variants by two lead acetate test protocols
      and multiplex PCR. The lead acetate test protocol 1 differed from protocol 2 by a
      lower inoculum size and different incubation conditions while the multiplex PCR
      utilized 2 sets of primers targeting the ATG start codon of the gene STM3356.
      Lead acetate protocol 1 discriminated 97.1% of the isolates as S. Paratyphi B dT+
      and 2.9% as dT while test protocol 2 discriminated all the isolates as S.
      Paratyphi B dT+. The multiplex PCR test identified all 105 isolates as S.
      Paratyphi B dT+ strains. The concordance of the lead acetate test relative to
      that of multiplex PCR was 97.7% and 100% for protocol 1 and 2 respectively. This
      study showed that S. Paratyphi B dT+ is a common causative agent of
      gastroenteritis in Malaysia while paratyphoid fever appears to be relatively
      uncommon. Multiplex PCR was shown to be a simpler, more rapid and reliable method
      to discriminate S. Paratyphi B than the phenotypic lead acetate test.

PMID- 22870597
TI  - Potential use of single measurement of serum progesterone in detecting early
      pregnancy failure.
AB  - Early pregnancy failure is a common pregnancy complication. In clinical practice,
      the time delay to distinguish viable from nonviable pregnancy is often
      distressing to patients and doctors. A highly sensitive and specific biomarker
      that accurately discriminates between viable and nonviable pregnancy would be
      useful for early intervention. Progesterone has been shown as a biomarker of
      early pregnancy failure. However the usefulness is still questionable due to the
      different cutoff values used. A study was conducted to determine the role of
      progesterone as a marker of early pregnancy failure and to establish the cut-off
      value in discriminating between viable and nonviable pregnancy. The study was
      carried out in the Obstetric and Gynecology Patient Admission Centre (OBPAC),
      Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for a period of twelve
      months. Ninety-five pregnant women of 13 weeks or less period of amenorrhoea
      (POA) were recruited. Fourteen normal pregnant women were controls. The patients
      with early pregnancy failure were classified according to types of abortion.
      Single measurement of serum progesterone was carried out during admission. The
      outcome of pregnancy was followed up until 22 weeks of POA to ascertain viability
      of the fetus. Median progesterone levels were significantly lower in women with
      nonviable pregnancies compared with viable pregnancy [10.7ng/ml (0.60-49.80) vs.
      45.9ng/ml (15.40-127.20) respectively, p<0.001]. Progesterone levels were also
      significantly lower in threatened abortion patients with outcomes of nonviable
      pregnancy compared with pregnancies that progressed on to the viability period
      [23.3 +/- 12.0 vs. 89.7 +/- 33.2 respectively, p<0.001]. At cut-off value of
      32.7ng/ ml, progesterone had 90% sensitivity with 75% negative predictive value
      and 92% specificity with 97% positive predictive value. The area under curve for
      progesterone was 0.95 (95% Confidence Interval, 0.903-0.990). In conclusion,
      these findings indicate that serum progesterone can be used as a marker for early
      pregnancy failure.

PMID- 22870598
TI  - Serum total protein, albumin and advanced oxidation protein products (AOPP)-
      implications in oral squamous cell carcinoma.
AB  - BACKGROUND: The role of oxygen free radicals in the initiation, promotion and
      progression of carcinogenesis and the protective role of anti-oxidant defenses
      have been the subject of much speculation in the recent past with conflicting
      reports in the literature. OBJECTIVES: The aim of this study was to measure the
      concentration/levels of serum total proteins, albumin and advanced oxidation
      protein products as markers of oxidative stress in sera of patients with an oral
      pre-cancerous lesion and frank oral cancer. MATERIALS AND METHODS: The study
      consisted of sera analysis of 30 new patients of histologically proven well
      differentiated, oral squamous cell carcinoma and 10 patients, clinically
      diagnosed with a potentially malignant epithelial lesion, speckled leukoplakia,
      aged between 40 to 60 years, in addition to 25 healthy controls. One way analyses
      of variance were used to test the difference between groups. The normality of
      data was checked before the statistical analysis was performed. RESULTS: The
      study revealed variations in sera levels of albumin and advanced oxidation
      protein products to be statistically significant (p<0.001). CONCLUSION: The
      results obtained emphasize the need for more studies with larger sample sizes to
      be conducted before a conclusive role could be drawn in favour of sera levels of
      total protein, albumin and advanced oxidation protein products as markers of
      diagnostic significance and of the transition from the various oral pre-cancerous
      lesions and conditions into frank oral cancers.

PMID- 22870599
TI  - Endolymphatic sac tumour.
AB  - We present a case of a papillary tumour at the cerebellopontine angle in a 41
      year-old man. He presented with left-sided facial and ear pain associated with
      dizziness, nystagmus and hearing loss. CT scan of the temporal bone showed a
      destructive tumour at the left cerebellopontine angle. Surgical excision was
      performed and the diagnosis of the endolymphatic sac tumour was made.
      Endolymphatic tumour is a low grade adenocarcinoma that originates from the
      endolymphatic sac. The definitive diagnosis requires a combination of clinical
      features, radiological finding and pathological correlation.

PMID- 22870600
TI  - Co-inheritance of compound heterozygous Hb Constant Spring and a single 
      alpha(3.7) gene deletion with heterozygous deltabeta thalassaemia: a diagnostic
      challenge.
AB  - Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common
      underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of
      deletional and non-deletional alpha (alpha) thalassaemias may result in various
      thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta
      (delta) gene abnormalities would result in improved clinical phenotype. We report
      here a 33-year-old male patient who was admitted with dengue haemorrhagic fever,
      with a background history of Grave's disease, incidentally noted to have mild
      hypochromic microcytic red cell indices. Physical examination revealed no
      thalassaemic features or hepatosplenomegaly. His full blood picture showed
      hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation
      of Hb using high performance liquid chromatography (HPLC) and capillary
      electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There
      was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer
      test was positive with heterocellular distribution of Hb F among the red cells.
      DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7)
      deletion and Hb CS mutation. These findings were suggestive of compound
      heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant
      heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(
      3.7) deletion is expected to result at the very least in a clinical phenotype
      similar to that of two alpha genes deletion. However we demonstrate here a
      phenotypic modification of alpha thalassemia presumptively as a result of co
      inheritance with deltabeta chain abnormality as suggested by the high Hb F level.

PMID- 22870601
TI  - Multiple metastatic renal cell carcinoma isolated to pancreas.
AB  - Renal cell carcinoma (RCC) metastases to the pancreas are reported to be rare.
      Isolated multiple pancreatic metastases are even rarer. We report a 68-year-old
      asymptomatic male patient who presented with multiple metastatic nodular lesions
      in the pancreas demonstrated by computerized tomography 3.5 years after radical
      nephrectomy performed for clear cell RCC. Spleen-preserving total pancreatectomy
      was performed. Gross examination revealed five well-demarcated tumoral nodules in
      the head, body and tail of the pancreas. Histopathological examination revealed
      clusters of epithelial clear cells, immunohistochemically positive for CD10 and
      vimentin, and negative for CK19 and chromogranin, supporting a diagnosis of
      metastatic RCC. The patient has remained well at 29 months post-resection, in
      agreement with recent experience that radical resection for multiple isolated
      metastatic nodular lesions can achieve improved survival and better quality of
      life.

PMID- 22870602
TI  - Factor IX mutations in haemophilia B patients in Malaysia: a preliminary study.
AB  - Haemophilia B is caused by coagulation defects in the factor IX gene located in
      Xq27.1 on the X chromosome. Identification of mutations contributing to defective
      factor IX may be advantageous for precise carrier and prenatal diagnosis. We
      studied 16 patients from 11 families, consisting of 8 patients of the Malay
      ethnic group, of which 6 were siblings. Factor IX mutations have not been
      previously reported in the Malay ethnic group. The functional region of the
      factor IX gene was sequenced and mutations were identified in either the exon or
      intronic regions in 15 of the patients. One novel mutation, 6660_6664delTTCTT was
      identified in siblings with moderate form of haemophilia B. Mutations identified
      in our patients when linked with disease severity were similar to findings in
      other populations. In summary, this preliminary data will be used to build a
      Malaysian mutation database which would facilitate genetic counseling.

PMID- 22870603
TI  - In-house diagnosis test research in Thailand.

PMID- 22870604
TI  - Editor's preface: Contact zones and safe houses.

PMID- 22870605
TI  - Hurry tomorrow: errata in a time of digital access.

PMID- 22870606
TI  - The accident and the beautiful: on Alan Shapiro's "The Accident".

PMID- 22870607
TI  - Narrative survival: personal and institutional accounts of asylum confinement.
AB  - This essay has been conceptually eclectic in that we have integrated concepts
      from genre theory and discourse analysis. In our interpretation of Merivale and
      Marshall's narratives, we have also drawn upon Frye's Anatomy of criticism, a
      canonical text in literary genre theory. Such an eclectic approach seems
      warranted by both the contextual and textual features of Merivale's and
      Marshall's narratives, and in particular by Merivale's use of Mennipean satire
      with its encyclopedic detail. In our discussion of Merivale and Marshall's
      Admissions Records we have drawn on speech act theory to suggest that the Order
      (to admit a patient), the two medical certificates that follow, and finally, the
      notice to admit a patient constitute a constellation of texts, a genre suite,
      with a powerful illocutionary force. These texts are the prelude to and the means
      of confinement; they are both act and process. At the heart of our comparison of
      the asylum records of Merivale and Marshall with their "survivor narratives" is
      our analytic conclusion that the Ticehurst case histories can be said to
      constitute a linear "chronicle" of what Hayes Newington, the writer of the two
      case histories observed and inferred about his two patients. As chronicles, the
      Ticehurst Asylum case histories are linear representations or realistic accounts.
      As such, these archival documents provide a genuine insight into the "ways that
      that reality offers itself to perception". The institutional accounts exist in-
      and mark a--"flat time," equalized by each dated entry depicting the writer's
      mechanical act of observing/noting in brief, stereotypical sentences, e.g.,
      "Patient is better [or, conversely, no] better today." We dubbed this metronomic
      time: beating regularly and evenly, flattening out the individual trajectories of
      each patient's illness. Metronomic time is normative. Each beat is calculated
      precisely to be the same as next. The dispassionate nature of clinical
      observations and the metronymic rhythms of the asylum fit with this flat,
      regular, uniform view of time. Once metronomic, institutional time is set in
      motion by the precipitating event of the certificates of insanity, entries are
      logged with regularity and observations are made in a formulaic, abbreviated, and
      predictable manner. By contrast, the passage of time recorded in both Merivale's
      memoir and Marshall's oral account is irregular, unpredictable, marked by acute
      catastrophes and long anxious periods of waiting for a resolution, by peaks of
      conflict and turmoil alternating with valleys of dazed stupor or inaction. Time
      in their accounts is also recursive; events are re-lived, sometimes more than
      once, as the patients recount their feelings about their confinement. Time for
      Merivale and Marshall (and presumably other patients as well) acquires a
      symphonic pattern: recursive, with dramatic highs and lows, unfolding multiple
      variations of a central theme-in both of these cases, denial of insanity. Both
      metronome and symphonic time have similar rhythmic "deep structures," but while
      one is simply a repetitive drumbeat of the quotidian, the other takes off into
      richer, more elaborate arrangements invested with personal meaning.

PMID- 22870608
TI  - Melancholia in Janet Frame's Faces in the Water.

PMID- 22870609
TI  - "These frightful sights would work havoc with one's brain": subjective
      experience, trauma, and resilience in first world war writings by medical
      personnel.

PMID- 22870610
TI  - Erectile dysfunction and the post war novel: The Sun Also Rises and In Country.

PMID- 22870611
TI  - Minding the gap(s): narrativity and liminality in medical student writing.

PMID- 22870612
TI  - "I feel like his dealer": narratives underlying a case discussion in a palliative
      medicine rotation.

PMID- 22870613
TI  - Did the novelist anticipate the neurologist? The enigma of George Eliot's The
      Lifted Veil.

PMID- 22870614
TI  - Brain memoirs, neuroscience, and the self: a review article.

PMID- 22870615
TI  - [Application progress of laser-induced breakdown spectroscopy for surface
      analysis in materials science field].
AB  - As a truly surface analytical tool, laser-induced breakdown spectroscopy (LIBS)
      was developed in recent ten years, and in this paper, fundamental theory,
      instrumentation and it's applications in material science are reviewed in detail.
      Application progress of elemental distribution and depth profile analysis are
      mainly discussed in the field of metallurgy, semiconductor and electronical
      materials at home and abroad. It is pointed out that the pulse energy, ambient
      gas and it's pressure, and energy distribution of laser beam strongly influence
      spatial and depth resolution, and meanwhile a approach to improving resolution
      considering analytical sensitivity is provided. Compared with traditional surface
      analytical methods, the advantage of LIBS is very large scanning area, high
      analytical speed, and that conducting materials or non-conducting materials both
      can be analyzed. It becomes a powerful complement of traditional surface
      analytical tool.

PMID- 22870616
TI  - [Spectral characteristic of short-arc xenon lamp and application in solar
      simulators].
AB  - Due to the inhomogeneous spatial spectral distribution of short-arc xenon lamp,
      its application is difficult. In the present paper, axially spectral distribution
      of xenon lamp was measured and temperature distribution was calculated, the
      temperature distribution was analysed as exponential relationship with arc
      current density. Therefore, xenon lamp spectral distribution can be made closer
      to the standard solar simulator spectral distribution by controlling current
      density.

PMID- 22870617
TI  - [A solar blind light source with long dynamic range].
AB  - In order to realize the irradiance calibration of SBUV-ICCD (solar blind
      ultraviolent Intensified change-coupled device) with dynamic range reaching 120
      dB, a light source with long dynamic range was designed and realized. Firstly,
      the irradiance dynamic range was estimated. Then using deuterium lamp,
      integrating sphere, precise stop and rail, an ultraviolent light source was
      developed, which has fixed structure of spectrum, but the irradiance can change
      continuously in long range. At last the light source's performance was tested.
      The result shows that the irradiance between 0.278 and 2.8 x 10(-7) microW x cm(
      2) was covered, and the stability was 0.93%/3 h. So the demand of calibration of
      irradiance was satisfied. It will help for measuring the surface uniformity of
      detector and the calibration of imaging systems.

PMID- 22870618
TI  - [Measurement of night sky spectral radiation and analysis of spectral denoising].
AB  - In spectral radiation detection, spectral characteristics of the environment are
      completely different from standard light sources, so the output characteristics
      of optical imaging device is bound to bring greater error due to spectrum
      matching in imaging characteristic analysis. In the present paper, we measured
      moon-light and star-light spectral radiation using a portable CCD fiber
      spectrometer, and analyzed spectral characteristics, which provided a reference
      to correctly evaluate the imaging performance of optical imaging device.

PMID- 22870619
TI  - [Monitoring spatio-temporal spectral characteristics of leaves of karst plant
      during dehydration using a field imaging spectrometer system].
AB  - As the supplement of spaceborne and airborne imaging spectrometer system, field
      Imaging spectrometer system spans a very broad range of applications. Imaging
      spectrometer system of this new kind could provide vital information especially
      for which spaceborne or airborne remote sensing could not be competent, such as
      proximal detection of plant population, individual plant or plant organs for site
      specific management in precision agriculture. A new self-developed imaging
      spectrometer system was utilized to monitor spatio-temporal dynamics of spectral
      changes of plant leaves in response to dehydration. lThe phenomenon of blue shift
      of red edge of plant leaves was successfully detected and visualized in the form
      of image series. The patterns of photochemical reflectance index (PRI) of leaves
      during dehydration were compared and confirmed by fluorescence parameter quantum
      yield. Our results show that FISS has good spectral and radiometric properties
      and could be used in quantitative researches and precise information mapping.

PMID- 22870620
TI  - [Characteristics of rubidium forward degenerate four-wave mixing (FDFWM)
      influenced by the matrix effect of chloride brine in graphite furnace].
AB  - Rb is mainly extracted from brine. The authors studied the matrix effect of
      chloride brine (NaCl, CaCl2, KCl and MgCl2) on FDFWM (Forward phase-matching
      degenerate four-wave mixing) of Rb in the graphite furnace. The Rb and other
      chloride brine concentrations dependences of FDFWM were investigated
      respectively. The results indicate that with the increase in Rb concentration,
      FDFWM increases and reaches the highest at 80 ng x mL(-1). With the concentration
      of Rb sample further increasing, the FDFWM intensity drops. It was also found
      that when the Rb concentration is low, FDFWM signal is suppressed by the chloride
      brine, and the suppressing effect gets stronger with the increase in the chloride
      brine concentration. However, when the Rb concentration is high, FDFWM signal is
      first enhanced and then suppressed with the increase in the chloride brine
      concentration. The Cl- interference and Rb ionization in the graphite furnace
      were employed to explain the experimental results. This work is of important
      meaning in extracting and analyzing Rb in brine.

PMID- 22870621
TI  - [Measurement of optical parameters of organic solvents by THz time-domain
      reflection spectroscopy].
AB  - Four kinds of organic solvents, including positive hexane, liquid paraffin, ethyl
      alcohol, and water, were measured by using terahertz time-domain reflection
      spectroscopy. According the experiment models, two methods can be used to extract
      optical parameters. Refractive index and absorption coefficient for these four
      solvents were extracted with two methods and were compared with the results
      obtained by transmission measurements, which verified that these methods are
      correct. This work solved the problem that the optical parameters of sample
      absorbing strongly terahertz cannot be measured and extracted by using terahertz
      time-domain transmission system.

PMID- 22870622
TI  - [Effects of gamma irradiation and O2-annealing on optical spectra of Bi doped
      cadmium tungstate crystal].
AB  - The Bi doped tungstate of cadmium crystals were O2-annealed at various
      temperature, and the absorption and emission spectra of O2-annealed Bi doped
      tungstate of cadmium crystals were investigated. The absorption intensity
      decreased, and the absorption side band was shifted to blue short wavelength as
      the increase of annealing temperature. The emissions at 528 nm and 1 078 nm were
      observed under excited by 373 and 980 nm, which they were attributed to the
      intrinsic emission of CdWO4 crystal and emission of Bi5+ ion, respectively. After
      the crystals were O2-annealed, the 528 nm emission intensity enhanced while the 1
      078 nm intensity reduced. It was attributed to the transformation of Bi5+ to Bi3+
      ions in the annealing process. After O2-annealed, the transmission of the crystal
      was enhanced obviously and the color of the crystal became weak. It is attributed
      to the decrease of oxygen vacancy (Vo) in crystal after the crystal was heated in
      O2 atmosphere. The 1 078 nm emission intensity reduced while the 528 nm intensity
      enhanced after the crystals were gamma-irradiated. It may be due to the
      transormation of Bi5+ to Bi3+ ions through evolution of gamma-irradiated.

PMID- 22870623
TI  - [Study on plasma parameters in diffuse discharge with semispherical electrod by
      optical emission spectrum].
AB  - The diffuse discharge plasma in air was observed in a dielectric barrier
      discharge with two semispherical water electrodes. The variations of vibration
      temperature, rotation temperature, and average electron energy as the function of
      the applied voltage were studied by emission spectroscopy. The vibration
      temperature and the rotation temperature were calculated through the second
      positive band system (C3Pi(u)-->B3Pi(g)) of N2+ and the first negative band
      system (B2 Sigma(u+)-->Chi2Sigma(g+)) of N(2+) respectively. The average electron
      energy was studied by intensity ratio of 391.4 and 337.1 nm. It was found that
      the rotation temperature increases with the applied voltage increasing, while the
      vibration temperature and the electron energy decrease.

PMID- 22870624
TI  - [Study of emission spectra of N atom generated in multi-needle-to-plate corona
      discharge].
AB  - The emission spectra of nitrogen (N) atom produced by multi-needle-to-plate
      negative corona discharge in air were detected successfully at one atmosphere,
      and the excited transition spectral line at 674.5 nm with maximum value of
      relative intensity was selected to investigate the influences of air and
      electrical parameters on N atom relative density. The results indicate that N
      atom relative density in ionization region increases with the increase in power;
      decreases with increasing discharge gap and relative humidity; and with the
      increase in N2 content, the relative density of N active atom firstly increases
      and then decreases. Under present experimental conditions, the maximum value of N
      atom relative density appears at the axial distance from needle point r = 1 mm.

PMID- 22870625
TI  - [Spectra line profile and vibrational temperature of bright dot and dark dot
      discharge in a dielectric barrier discharge].
AB  - The emission spectrum line shift and vibrational temperature of the bright dot
      and dark dot discharges, which are observed in the argon and air dielectric
      barrier discharge at high temperature for the first time were measured and
      compared. The line shift of the spectral line of the Ar I (2P2-->1S5) is measured
      and the vibrational temperature was calculated using by the emission spectral
      lines of the N2 second positive band system (C3Pi(u)-->B3Pi(g)). The results show
      that the spectrum line shift of the bright dot discharge channel is larger than
      that of the dark dot channel, which indicates that the former has higher electron
      density compared to the latter, and the vibrational temperature of the dark dot
      discharge channel is higher than that of the bright dot discharge channel.

PMID- 22870626
TI  - [The changing process of population probability and fluorescence intensity in
      ErP5O14 noncrystalline from 0 second to stabilization].
AB  - The results of numerical simulation were compared respectively with and without
      considering the improved coefficient for the energy transfer process in ErP5O14
      noncrystalline under 521.8, 450.0, 405.5 and 378.5 nm lights excitation. The
      results showed that it is essential to take the coefficient into calculation
      where energy transfer plays a key role. The relative fluorescence intensity
      ratios of 4I13/2-->4I15/2 to 4I11/2-->4I15/2 under 523.8, 450.0 and 378.5 nm
      lights excitation were 2.11, 2.82 and 2.99 times larger than that under 979.3 nm
      light excitation respectively. There are obviously effective near-infrared (NIR)
      quantum cutting of 4I13/2-->4I15/2 transition. The result indicates that ErP5O14
      noncrystalline has potential application in the enhancement of conversion
      efficiency of germanium solar cells.

PMID- 22870627
TI  - [Gd-doped natural thenardite: Eu photoluminescence properties of europium].
AB  - The authors prepared Na2SO4: Eu, Gd, and Na2Gd2 (SO4)4: Eu phosphors by heating,
      the mixed powder of GdF3, EuF3 and natural mirabilite with muffle furnace at 1
      000 degrees C for 30 min and continually heating it with microwave at 750 degrees
      C for 10 min. With increasing the concentrations of Gd ion, the 610 nm emission
      intensity due to Eu3+ was strengthened. Gd3+ probably formed a bridge between
      substrate and the activator so that the energy is able to be transferred
      efficiently. The luminescence intensity, along with colorimetric purity, reaches
      the top with 21 mol% Gd3+ doping in the thenardite (Na2SO4: Eu) lattices,
      eventually coming up the quenching effects of concentration.

PMID- 22870628
TI  - [Study on the effect of temperature on the conformation of cross-linked collagen
      by two-dimensional infrared correlation spectroscopy].
AB  - The Fourier transform infrared spectroscopy and two dimensional correlation
      analysis method were applied to study a denaturing process of uncross-linked
      collagen and cross-linked collagen during varying temperature. It was found that
      the intensity of typically characteristic absorptions of collagen decreased and
      its peak shifted to low frequency, The amide II central absorbance peak moved to
      a lower frequency by about  10 cm(-1), which indicated that the inter-chain
      hydrogen bonds which stabilized the triple helix conformation of collagen were
      disrupted during thermal denaturation, resulting in a conformational change. The
      intensity of auto-peak at 1 515 cm(-1) was maximum, which suggested that the
      temperature had a big impact on amide II. In comparison with uncross-linked
      collagen, the intensity of cross-peaks of cross-linked collagen was weaker, which
      demonstrated that the effect of temperature on the structure of cross-linked
      collagen was smaller, and the thermal stability properties of collagen solution
      could be improved by cross-linking. While the order of second structure changes
      of cross-linked collagen was different. These fundamental data should provide
      available information for understanding the relationship between the structure
      and function of cross-linked collagen.

PMID- 22870629
TI  - [Study on specificity of noninvasive glucose measurements based on two
      dimensional correlation mid-infrared spectroscopy].
AB  - Glucose specificity is the premise of spectroscopic measurements of blood glucose
      concentration, and it is also paramount for feasibility study of a spectral
      measurement method. Two-dimensional correlation spectroscopy technology is widely
      used in many fields such as inter-/intra-molecular reaction, material phase
      transition and information extraction because of its high resolution and
      effective Noda's rule. In the present paper, the glucose specificity for
      noninvasive glucose measurements by mid-infrared spectra based on the 2D
      correlation spectroscopy was investigated. First, the feasibility of this method
      was validated by a series of in vitro experiments of glucose. Then the in vivo
      experiments of four volunteers were conducted and the characteristic information
      of glucose by mid-infrared spectra collected from human fingers was confirmed by
      2D correlation spectroscopy analysis.

PMID- 22870630
TI  - [Study on the micro-infrared spectra and origin of polycrystalline diamonds from
      Mengyin kimberlite pipes].
AB  - The natural polycrystalline diamonds from the Mengyin kimberlite pipes can be
      classified as the euhedral faceted polycrystalline diamonds and anhedral rounded
      polycrystalline diamonds. The results of micro-FTIR spectra characterization of
      the polycrystalline diamonds show that the concentration of nitrogen is low,
      varying from 16.69 to 72.81 microgram per gram and is different among different
      diamond grains or position in polycrystalline diamonds. The euhedral faceted
      polycrystalline diamonds are Ia AB type and have higher concentration of A-center
      defects than B-center defects. Most of the anhedral rounded polycrystalline
      diamonds are Ia AB type and have higher content of B-center defects. A minority
      of the anhedral rounded polycrystalline diamonds have C-center, A-center and B
      center defects simultaneously. The polycrystalline diamonds probably originated
      from the relatively deeper mantle and were not formed in diamond nucleation
      stage, but in the diamond growth period or some special conditions after the
      diamond grains were formed already. Furthermore, the euhedral faceted
      polycrystalline diamonds were formed slightly later and the anhedral rounded
      polycrystalline diamonds were formed obviously earlier than the diamond single
      crystals from the Mengyin kimberlite pipes.

PMID- 22870631
TI  - [Analysis of the character of film decomposition of starch acetate (SA) coated
      urea by infrared spectrum].
AB  - The degradability characteristics of film with 4 kinds of starch acetate coated
      and inhibitors amended urea were analyzed by FTIR, which was purposed to supply
      theoretical basis for applying starch acetate coated urea fertilizers in farming.
      The result showed that the chemical component, molecule structure and material
      form of the membrane were not changed because of adding different inhibitors to
      urea. The main peaks of the film degradation process were brought by the H--O, -
      OH, CO2, C==O, --CH2, --CH3, C--O, C--O--H and C--O--C vibrancy in asymmetry and
      symmetry. In brown soil, the trend of absorbing value of the most high peak was
      0>15>30>60>90>120>150>310 d. The infrared spectra of 4 kinds of fertilizers were
      not different remarkably, and the film was comparatively slowly degraded before
      15 d. But a majority of the film had been already degraded after 150 days. The
      main components of film materials were degraded fastest in 310 days. The speed of
      film degradation wasn't more impacted by different inhibitors. The characteristic
      of starch acetate film degradation may be monitored entirely and degradation
      speed difference of the film could be represented through infrared spectrum.

PMID- 22870632
TI  - [Maturity qualitative discrimination of small watermelon fruit].
AB  - Dividing watermelons into two categories as not complete mature and fully mature
      by cluster analyzing the 10 indicators associated with maturity, the two modeling
      methods PCADA and PLSDA were used, and through the near-infrared spectroscopy,
      the maturity of small watermelon fruit JINGXIU was qualitatively determined. The
      PCADA model is the best. Modeling at the top position is better than that of the
      equatorial parts of the melon. The two models both have a miscarriage of justice,
      and exists the same sample with a miscarriage of justice. Fruit samples of
      different physical and chemical composition and structure will have an impact on
      the spectral information, resulting in miscarriage of justice. Near-infrared
      diffuse transmittance technique can get better results in detection of small
      watermelon maturity. But the prediction model should be established to select the
      appropriate parts of the spectrum acquisition and modeling methods.

PMID- 22870633
TI  - [The utility research on NIR diffuse reflectance and transmittance measurements
      mode in authenticity identification of maize population samples].
AB  - In the present paper, the spectral measurements of maize population samples were
      researched so as to identify their authenticity. Diffuse reflectance and
      transmittance measure modes were used to collect spectral data of 8 maize
      varieties. DPLS-DA was used to compress pretreated data. The recognition models
      of eight maize varieties were built based on biomimetic pattern recognition
      (BPR). The average correct recognition rate and average correct rejection rate of
      identification models built by two modes were calculated. The average recognition
      rate and rejection rate of diffuse reflectance method reached 94.50% and 96.71%,
      and those of transmittance method reached 98.5% and 98.00%, respectively. Both of
      them met the requirements of maize preliminary screening, and the recognition
      rate and rejection rate of transmittance method are higher than diffuse
      reflectance method by 4% and 1.3% respectively.

PMID- 22870634
TI  - [Infrared spectroscopy analysis of SF6 using multiscale weighted principal
      component analysis].
AB  - Infrared spectroscopy analysis of SF6 and its derivative is an important method
      for operating state assessment and fault diagnosis of the gas insulated
      switchgear (GIS). Traditional methods are complicated and inefficient, and the
      results can vary with different subjects. In the present work, the feature
      extraction methods in machine learning are recommended to solve such diagnosis
      problem, and a multiscale weighted principal component analysis method is
      proposed. The proposed method combines the advantage of standard principal
      component analysis and multiscale decomposition to maximize the feature
      information in different scales, and modifies the importance of the eigenvectors
      in classification. The classification performance of the proposed method was
      demonstrated to be 3 to 4 times better than that of the standard PCA for the
      infrared spectra of SF6 and its derivative provided by Guangxi Research Institute
      of Electric Power.

PMID- 22870635
TI  - [Detection and analysis of alcohol near-infrared spectrum in vitro and vivo based
      on wavelet transform].
AB  - The near-infrared spectroscopy (NIRS) signals of alcohol in vivo are always
      contaminated by noise. In the present study, wavelet analysis was used to
      eliminate noise and thereby detecting the NIRS signals of alcohol in vivo. In
      soft and hard threshold function, the spectral signals were de-noised by default
      threshold, Birge-Massart threshold and mini&max threshold respectively. Signal
      noise ratio (SNR) and root mean square error (RMSE) method were used to evaluate
      the effects of the de-noising. The results show that the default threshold de
      noising has the best effects. Therefore, the default threshold de-noising was
      chosen to perform de-noising analysis in vivo and in vitro. Our result shows that
      the wavelet transform de-noising is effective in removing noise from NRS signals
      of alcohol in vivo. With different alcohol concentration, the de-noising spectrua
      can show evident absorption peaks. Wavelet analysis is an effective method in the
      non-invasive alcohol testing and quantitative analysis.

PMID- 22870636
TI  - [Qualitative detection of bottled vinegar based on NIR spectroscopy technique].
AB  - To evaluate the applicability of non-invasive near infrared reflectance (NIR)
      spectroscopy for detection of bottled vinegar, transmission spectra of bottled
      vinegar samples were obtained and compared with the spectra obtained by using
      cell detection method, where samples were titrated in the fixed liquid cell with
      a 1.0 mm light path length. The result shows that, the spectra obtained by the
      two different methods have obvious differences in the near infrared region.
      Firstly, the spectra obtained by using bottled detection method have no
      absorption peak at 1 480 and 1 900 nm, and furthermore, it has absorption peak at
      1 660 nm. Secondly, the max. absorbance value of bottled detection is less than
      4, while with the cell detection it is near 6. It indicates that glass packaging
      has influence on the detection of bottled vinegar. The 1st derivative method was
      put forward to eliminate this influence, and then qualitative analysis model was
      obtained by using principal component analysis-artificial neural net work. The
      precision of prediction result achieved 100%. This research shows that 1st
      derivative can eliminate the influence of glass packaging, and realize the
      qualitative analysis of bottled vinegar.

PMID- 22870637
TI  - [Recognition of corn seeds based on pattern recognition and near infrared
      spectroscopy technology].
AB  - Pattern recognition technology and data mining methods have become a hot topic in
      chemometrics. Near infrared (NIR) spectroscopic analysis has been widely used in
      spectrum signal processing and modeling due to its advantages of quickness,
      simplicity and nondestructiveness. Based on five different methods of pattern
      recognition, namely the locally linear embedding (LLE), wavelet transform (WT),
      principal component analysis (PCA), partial least squares (PLS) and support
      vector machine (SVM), the pattern recognition system for corn seeds is proposed
      using NIR technology, and applied to classification of 108 hybrid samples and 178
      female samples for corn seeds. Firstly, we get rid of noise or reduce the
      dimension using LLE, WT, PCA and PLS, and then use SVM to identify two-class
      samples. In the meantime, 1-norm SVM is the method of direct classification and
      identification. Experimental results for three different spectral regions show
      that the performances of three methods, i. e. PCA+SVM, LLE+SVM, PLS+SVM, are
      superior to WT+SVM and 1-norm SVM methods, and obtain a high classification
      accuracy, which indicates the feasibility and effectiveness of the proposed
      methods. Moreover, this investigation provides the theoretical support and
      practical method for recognition of corn seeds utilizing near infrared spectral
      data.

PMID- 22870638
TI  - [Research on detection method of adulterated olive oil by Raman spectroscopy and
      least squares support vector machine].
AB  - For the purpose of the authentication of sorts as well as the prediction of
      contents of the oils which were adulterated into olive oil, 117 olive oil samples
      adulterated with sunflower seed oil, soybean oil and corn oil were detected by
      Raman spectroscopy, and least squares support vector machine (LS-SVM) based on
      multiple iterative optimization was used to identify the type of the adulterant
      oil, and the composite recognition rate was 97%. In addition, methods such as LS
      SVM, ANNs and PLSR were used to build the Raman spectra calibration model of the
      adulterant oil (sunflower seed oil, soybean oil and corn oil) contents
      respectively, the results indicated that LS-SVM had the best predictive
      performance, and the root mean square error of prediction (RMSEP) ranged from
      0.007 4 to 0.014 2. Research results showed the method based on Raman
      spectroscopy and LS-SVM was accurate, fast, simple and non-destructive for
      adulterated olive oil detection.

PMID- 22870639
TI  - [Poly (allylamine)-stabilized colloidal copper nanoparticles: synthesis and their
      SERS activities].
AB  - Poly(allylamine)-stabilized spherical and rod-shaped copper nanoparticles were
      synthesized by a simple chemical reaction. The synthesis was performed by the
      reduction of copper (II) salt with hydrazine in aqueous solution under
      atmospheric air in the presence of poly(allylamine) (PAAm) capping agent. Besides
      providing long-term stability to the nanoparticles by preventing particle
      agglomeration, polymer capping agents such as PAAm make the particles dispersible
      in aqueous solution. Noteworthy advantages of the synthetic method include its
      production of water dispersible nanoparticles at room temperature without inert
      atmosphere, making the synthesis more environmentally friendly. The resulting
      copper nanoparticles were investigated by UV-Vis spectroscopy and transmission
      electron microscopy. The authors found that several factors, including the amount
      of NaOH solution, concentration of PAAm, and reaction time, affect the
      composition, size, morphology, and degree of agglomeration of the resulting
      copper nanoparticles. The amount of NaOH in the reaction is crucial for the
      synthesis to result in either pure copper or copper oxide-containing copper
      nanoparticles as well as to produce the highest possible yield of copper
      nanoparticles. In addition, the reaction time and concentration of PAAm play key
      roles in controlling the size and shape of the nanoparticles, respectively. The
      resulting colloidal copper nanoparticles exhibit large surface-enhanced Raman
      spectroscopy (SERS) signals.

PMID- 22870640
TI  - [Research on using 3-D fluorescence spectroscopy-wavelet transform-PSO for rapid
      discrimination of compositions of phytoplankton population].
AB  - Three-dimensional fluorescence of 17 red tide algae species that belong to 13
      genera of five divisions was measured by fluorescence excitation-emission matrix
      spectroscopy. And 2-D wavelet db7 was selected to decompose the spectra at
      different levels to choose the alternative characteristic spectra. Based on the
      norm reference spectra constructed by cluster analysis, the linear regression
      model was solved by particle swarm optimization (PSO) algorithm and the
      discrimination method was established at the division and genus level. Some
      samples were tested: for single algal samples, and the correct discrimination
      ratios (CDRs) were 96.1% and 73.6%, respectively; For simulative mixed algal
      samples, when the dominance were 60%, 75%, 80% and 90% of the total biomass, the
      CDRs of the dominant algae were 86.7%, 96.9%, 98.7% and 99.4% with the average
      relative contents of 62.6%, 72.7%, 76.0% and 81.6%, respectively at the division
      level. And the CDRs were 51.0%, 68.9%, 72.0%, and 78.8% at the genus level,
      respectively. For 364 actual mixture samples, the CDRs of the dominant species
      (75%) were 99.4% at the division level and 75.9% at the genus level . For the
      particular field samples from mesocosm experiment and corrected from Jiaozhou
      Bay, results showed that the method can be used to realize the identification of
      red tide algae population and estimate the relative abundance of different
      classes, especially between diatoms and dinoflagellates.

PMID- 22870641
TI  - [The quantification of gemifloxacin by fluorescence quenching method using
      chitosan-coated CdTe quantum dots].
AB  - Chitosan-coated CdTe quantum dots can reduce QDs toxicity and enhance its
      stability in aqueous solution. Chitosan-coated CdTe QDs were used as fluorescence
      probes to determine Gemifloxacin on the basis of fluorescence quenching method.
      The results indicated that the relative fluorescence intensity was linearly
      proportional to the Gemifloxacin concentration in the range of 3.46 x 10(-9)-3.46
      x 10(-7) g x L(-1) with a linear fitting equation of F0/F= 1.0637 + 0.016 7c(g x
      L(-1)) and the RSD was 2.7%. On the basis of fluorescence quenching method
      theory, it was concluded that the interaction between QDs and Gemifloxacin was a
      kind of static quenching through hydrogen bonding and Van der Waals force, and
      the binding sites value was 0.8. This method with high sensitivity and broad
      linear range provided a new approach to determining Gemifloxacin.

PMID- 22870642
TI  - [3D-EEM fluorescence characteristics of different fraction of dissolved organic
      matter in landfill leachate].
AB  - Three-dimensional excitation emission matrix fluorescence spectroscopy (3D-EEM)
      was applied to analyze the fluorescence characterization of dissolved organic
      matter in landfill leachate. The results showed that fulvic-like, tryptophan-like
      and humic acids-like matters were the main compounds in landfill leachate. A
      number of UV fulvic-like matters led to ineffective biodegradation of leachate.
      HOA contained more UV fulvic-like and less Vis fulvic-like, by contrary to HIA;
      HIN was mainly composed of UV fulvic-like and Vis fulvic-like matters; HOB, HIB
      and HIN had more intense fluorescence signal, whose fluorescence peaks occurred
      in the region of fulvic-like, tryptophan-like and humic acids-like. This was
      similar to the original leachate as well as HON which had relatively weak
      fluorescence signal. Moreover, different fractions had different fluorescence
      signal intensity in different regions. HOB and HIB had more intense signal in the
      region of UV fulvic-like. HIN had more intense signal in the region of UV fulvic
      like and Vis fulvic-like. HON had moderately intense signal in the whole region.
      HOA and HIA had relatively weak fluorescence signal.

PMID- 22870643
TI  - [Comparison of quasi-continuous and continuous tunable diode laser absorption
      spectroscopy for gas detection].
AB  - The theoretical analysis of the direct absorption spectroscopy, the continuous
      modulation spectroscopy and the quasi-continuous modulation spectroscopy was
      shown and the corresponding experiments were carried out in order to choose the
      adequate scheme of the laser modulation spectroscopy to satisfy different
      requirements of the detection. CO2 gas with different concentrations was detected
      under the same experimental conditions by using the three different modulation
      techniques with the same laser. Technical characteristics, signal features and
      detection limits were compared respectively. Results showed that the detection
      limit of the quasi-continuous modulation spectroscopy was approaching to that of
      the continuous modulation spectroscopy. However the linear distortion of the
      detection signal was obvious, because of the effects of laser energy intermittent
      and parasitic amplitude modulation on the line shape. Therefore the quasi
      continuous modulation spectroscopy is not suitable for the pressure and flow
      measurements, which closely depend on the line shape. This work has provided
      reference for selections of the laser modulation spectroscopy.

PMID- 22870644
TI  - [Spectral characteristics of dissolved organic matter released during the
      metabolic process of small medusa].
AB  - The metabolic processes of jellyfish can produce dissolved organic matter (DOM)
      which will influence the functioning of the aquatic ecosystems, yet the optical
      properties of DOM released by jellyfish are unknown. Here we report the
      absorption and fluorescence properties of DOM released by a medusa species Black
      fordia virginica during a 24 h incubation experiment. Compared with the control
      group, an obvious increase in the concentrations of dissolved organic carbon
      (DOC), absorption coefficient (a280) and total dissolved nitrogen (TDN) was
      observed in incubation group. This clearly demonstrated the release of DOM,
      chromophoric DOM (CDOM) and dissolved nutrients by B. virginica which feed on
      enough of Artemia sp. before the experiment. The increase in spectral slope ratio
      (SR) and decrease in humification index (HIX) indicated that the released DOM was
      less-humified and had relatively lower molecular weight. Parallel factor analysis
      (PARAFAC) decomposed the fluorescence matrices of DOM into three humic-like
      components (C1-C3) and one protein-like component (C4). The Fmax of two
      components (C2: < 250, 295/386 nm; C4: 275/334 nm) with the emission wavelength <
      400 nm increased significantly during the metabolic process of B. virginica.
      However, the Fmax of the other two components with the emission wavelength > 400
      nm showed little changes. Thus, we suggested a zooplankton index (ZIX) to trace
      and characterize the DOM excreted by metabolic activity of zooplankton, which is
      calculated as the ratio of the sum of Fmax of all fluorescence components with
      the emission wavelength < 400 nm to the sum of Fmax of the other components with
      the emission wavelength > 400 nm.

PMID- 22870645
TI  - [Spectroscopy of Ag(I), Cd(II) complexes with 4-mercaptopyridine].
AB  - In the present article, two kinds of metal-organic coordination compounds were
      synthesized between 4-mercaptopyridine (4-MPy) and nitrate of Ag(I) and Cd(II) by
      a general solution reaction and evaporation. 4-mercaptopyridine and two
      transition metal complexes were investigated by means of infrared, Raman and
      ultraviolet-visible spectroscopic techniques, respectively. Assignments of the
      main FTIR and Raman bands were carried out in detail. The relationship between
      those characteristic bands and the structure of ligands and coordination
      compounds was discussed. In the FTIR spectra, the co-vibration absorption band of
      nu(C==C) and nu(C==N), for 4-MPy at 1 459 cm(-1) blue-shifted to 1 464 cm(-1) for
      both the metal-organic coordination compounds, respectively. The Raman spectra,
      for the two coordination compounds, at 1 004 and 1 008 cm(-1), which can be
      assigned to ring breathing vibration, at 1 617 and 1 615 cm ', which can be
      assigned to ring flex vibration, and at 720 and 720 cm(-1), which can be assigned
      to the composite vibration of beta(C--C) and nu(C--S) are similar, respectively.

PMID- 22870646
TI  - [The study of spectral characteristics of several organophosphate pesticides].
AB  - Using Edinburgh FLS920P spectrometer, the authors obtained the UV-visible
      spectrum and fluorescence spectrum of parathion, metaphos and isocarbophos in
      their solution of methanol and ethanol respectively, and discussed their spectral
      characteristics and their mechanisms. Results show that they all have obvious
      absorption and fluorescence under the excitation of ultraviolet. The absorption
      peaks of parathion, metaphos and isocarbophos in their methanol and ethanol
      solution respectively are at 304 nm/298 nm, 304 nm/304 nm and 286 nm/286 nm. The
      peak wavelengths of fluorescence are at 404 nm/403 nm, 407 nm/ 402 nm and 423
      nm/415 nm, fitting fluorescence characteristics of conjugated aromatic compounds
      that the peak will have red shift with the increasing solvent polarity. The
      results may contribute to the application of spectral technique in the
      distinction of pesticides and detection of residues of pesticides in the area of
      food security supervision.

PMID- 22870647
TI  - [Research on fast experimental measurement method for atmosphere downward long
      wave radiance].
AB  - Direct measurement of the sky radiation in the direction of a special zenith
      angle as the average downward radiation is the fastest instantaneous downward
      radiation measurement. But this method has not been widely used, because there is
      no accu rate method for determining special zenith angle. The present paper
      analyzed the special angle with the variation of the aerosol optical thickness
      and atmospheric temperature and humidity through simulation by radiative transfer
      model. The results show that the special angles will be affected none by aerosols
      in clear skies, very little by atmospheric temperature, but significantly by
      atmospheric water vapor content. Therefore, the special angle could be determined
      only by atmospheric water vapor content in downward radiance infrared
      spectroscopy measurements in clear sky conditions. The downward radiation
      measurements results in western desert region indicate that the special angles
      determined by local atmospheric water vapor content are the same as experimental
      results. Besides, the error caused by taking the radiance at the special angle as
      the integral radiance meets the accuracy requirements. Accordingly, this fast
      measurement method can be widely used in field experiments while the special
      angle can be determined by atmospheric water vapor of the study area, since it
      can measure instantaneous downward radiance conveniently and accurately.

PMID- 22870648
TI  - [A modulation method to improve the signal-to-noise ratio of internal virtual
      hyperspectrum of body surface].
AB  - Virtual internal hyperspectrum of body surface which can express and properly mix
      the information of skin's composition and structure was expected to apply in the
      human disease quick-diagnosis, but the weak detected signal was easily impacted
      by ambient light and dark current from the instrument, so square wave modulated
      by chopper disk was proposed to resolve this issue. First, we built the
      experiment platform, and selected both laser and bromine tungsten lamp as the
      light source, then compared the virtual hyperspectrum of non-modulated and
      modulated light on human arm in the environment with artificial interference, and
      demodulated the modulated signal by FFT method. The experiment result showed that
      modulation method could effectively eliminate the impact brought by environmental
      light and dark current and improve the signal to noise ratio (SNR), suggesting a
      new approach to detect human's weak optical signals.

PMID- 22870649
TI  - [The research on multi-spectral fitting of LED spectrum tunable light source].
AB  - Using a number of different spectral LED cells, the spectra of several typical
      spectral light source were fitted successfully. The research focuses on how to
      find the needed spectral distribution and the least number of LEDs by using the
      target spectrum to go. Furthermore the result is used to judge and improve the
      obtained original fitting model. Simulate The target spectrum obtained by the
      actual measurement was simulated and preferable prospective result was obtained.

PMID- 22870650
TI  - [Quantitative inversion of rock SiO2 content based on thermal infrared emissivity
      spectrum].
AB  - The present paper used the emissivity of non-processed rocks measured by M304, a
      hyperspectral Fourier transform infrared (FTIR) spectroradiometer, and SiO2
      content by the X-ray fluorescence spectrometry. After continuum removal and
      normalization, stepwise regress method was employed to select the feature bands
      of rocks emissivity. And then quantitative relationship between SiO2 content and
      continuum removal emissivity of feature bands was analysed. Based on that, by
      comparing twelve SiO2 indices models, the optimal model for predicting SiO2
      content was built. The result showed that the SiO2 indices can predict SiO2
      content efficiently, and especially the normalization silicon dioxide index
      (NSDI) about 11.18 and 12.36 microm is the best; compared with regression models,
      NSDI is simpler and has higher practicality; the result has an important
      application value in rock classification and SiO2 content extraction with high
      precision.

PMID- 22870651
TI  - [Study on hyperspectral response to surface alteration by oil and gas
      microseepage under loess area].
AB  - The present takes the Qingyang, Gansu as an example, based on the mechanism of
      oil-gas microseepage, the spectra of the loess samples were measured, and the
      contents of carbonate minerals, clay minerals, Fe2+ and Fe3+, were analyzed. From
      their contents, it was shown that the carbonate mineralization and the red fading
      phenomenon are obvious for the known oil-gas field. Meanwhile, the parameters of
      absorption spectra of the loess samples were identified after the continuum was
      removed. The multiple regression analysis between the spectrum parameters
      (independent variables) and the mineral contents (the dependent variables) was
      implemented. The results indicate that the absorption depth is more sensitive.
      Thus, by their spectrum absorption parameters, 14 spectra of loess samples were
      clustered into two groups: samples in the known oil-gas field and unknown oil-gas
      field.

PMID- 22870652
TI  - [Study on varieties identification of Kentucky bluegrass using hyperspectral
      imaging and discriminant analysis].
AB  - Hyperspectral images of six varieties of Kentucky bluegrass were acquired using
      hyperspectral imager (550-1 000 nm) and the leaf spectral properties were
      extracted. Wilks' lambda stepwise method was used and 9 optimal wavelengths were
      selected from the original 94 wavelengths and the discriminant models for
      varieties identification of Kentucky bluegrass were built based on Fisher' s
      linear discriminant function. The results showed that the Fisher' s linear
      discriminant model with 9 wavelengths achieved classification accuracies of 100%
      for both training and testing samples. While for the models with three
      wavelengths and six wavelengths, classification accuracies reached 83.3% and
      96.7% for the testing samples, respectively. It indicates that hyperspectral
      images combined with discriminant analysis might be a good method to identify the
      varieties of Kentucky bluegrass.

PMID- 22870653
TI  - [Improving signal to noise ratio of spectroscopy for tongue inspection by
      reflectivity normalization method].
AB  - In order to solve the problem that the collected spectrum was influenced
      seriously by the operation method, improve the instrument sensitivity and enhance
      the differences between samples, reflectivity normalization method was used for
      data preprocessing in the present article. First, the reflect spectrum of tongue
      was collected, then the reflectivity and the normalized reflectivity of the
      samples were compared, and it was found that reflectivity normalization method
      can eliminate the impact brought by the collection from different distance. At
      the same time, the classification results between the reflectivity and the
      normaliza tion reflectivity of the different samples were compared, and the
      results showed that the reflectivity normalization method can enhance differences
      between the samples and enhance model's robustness and prediction ability of
      subsequent disease screening.

PMID- 22870654
TI  - [Advances in the research on hyperspectral remote sensing in biodiversity and
      conservation].
AB  - With the species reduction and the habitat destruction becoming serious
      increasingly, the biodiversity conservation has become one of the hottest topics.
      Remote sensing, the science of non-contact collection information, has the
      function of corresponding estimates of biodiversity, building model between
      species diversity relationship and mapping the index of biodiversity, which has
      been used widely in the field of biodiversity conservation. The present paper
      discussed the application of hyperspectral technology to the biodiversity
      conservation from two aspects, remote sensors and remote sensing techniques, and
      after, enumerated successful applications for emphasis. All these had a certain
      reference value in the development of biodiversity conservation.

PMID- 22870655
TI  - [The polarization characteristics distribution and correction method of the
      polarization coupling error in ocean remote sensing system].
AB  - With the development of the quantitative researches using ocean color remote
      sensing data sets, study on reducing the uncertainty of the response of the ocean
      color remote sensors to the polarization characteristics of the target has been
      attracting more and more attention recently. Taking MODIS as an example, the
      polarization distribution in the whole field of view was analyzed. For the
      atmosphere path radiance and the apparent radiance considering the coupling
      between ocean surface and atmosphere, the polarization distribution has a strong
      relation with the imaging geometry. Compared to the contribution of the
      polarization from the rough sea surface, the contribution from the atmosphere is
      dominated. Based on the polarization characteristics in the field of view, the
      influence of the polarization coupling error on the quality of the satellite data
      was studied with the assumption of different polarization sensitivities. It was
      found that errors due to polarization sensitivity in the field of view are lower
      than water leaving radiance only when the polarization sensitivity is less than
      2%. And in this case it can meet the need of the retrieval of water leaving
      radiative products. The method of the compensation for the polarization coupling
      error due to the atmosphere is proposed, which proved to be effective to improve
      the utilization of satellite data and the accuracy of measured radiance by remote
      sensor.

PMID- 22870656
TI  - [Monitoring gas concentration from carbon emissions by remote sensing].
AB  - Global climate warming has become the focus question of international global
      climate change research, and is an important factor influencing world economy,
      political situation, and ecological environment. Produced carbon emission gases
      such as CO2, CH4, N2O, etc. caused by human activity are the main reason for
      global warming. In order to forecast future climate change and construct accurate
      carbon cycle model, monitoring accuracy of gas concentration from carbon emission
      must be improved. In the present paper, the newest progress in the international
      research results about monitoring gas concentration from carbon emissions by
      remote sensing was considered, monitoring method for carbon emissions was
      introduced, and remotely sensed monitoring technology about gas concentration
      from carbon emissions (including thermal infrared, sun spectrum, active remote
      sensing monitoring technology) was stated. In detail, several present and future
      satellite sensors were introduced (including TOVS, AIRS, IASI, SCIAMACHY, GOSAT,
      OCO, A-SCOPE and ASCENDS), and monitoring results achieved by these sensors were
      analyzed.

PMID- 22870657
TI  - [Retrieval of dust fraction of atmospheric aerosols based on spectra
      characteristics of refractive indices obtained from remote sensing measurements].
AB  - Mineral dust is an important chemical component of aerosol, which has a
      significant impact on the climate and environmental changes. The spectral
      behavior of aerosol refractive indices at four wavelengths from 440 to 1 020 nm
      was analyzed based on one year observation obtained from Beijing AERONET site.
      The real parts of refractive index (n) in each band did not differ greatly,
      however the imaginary parts (k) showed a significant difference due to the
      absorption of mineral dust in aerosol. From 440 to 670 nm k decreased rapidly,
      while from 670 to 1 020 nm featured a lower, constant value. Accordingly, k(440
      nm) could be considered separately with other three bands. Hence, we added
      mineral dust into the currently used three-component aerosol chemical model to
      form a new four-component model (i. e. BC, AS, dust and water) which is more
      suitable to represent the aerosol chemical composition. Then we presented a
      method to retrieve dust content in aerosols using this four-component model and
      refractive indices obtained from the sunphotometer measurements. Finally the dust
      content in aerosol was investigated under different weather conditions, i. e.
      clear, haze and dust in Beijing. The results showed that volume fractions of the
      dust component were 88%, 37% and 48% for clear, hazy and dusty day respectively,
      which was consistent with the coarse mode proportion in aerosols calculated from
      aerosol size distributions.

PMID- 22870658
TI  - [Preparation and performance of controlled-release tablets of sasanquasaponin
      casein].
AB  - The controlled-release tablets of sasanquasaponin (SQS)-casein were prepared by
      using SQS, casein and guar gum as the main drug and accessory materials
      respectively. The method of determination of SQS in the controlled-release
      tablets of SQS-casein, and the effects of release media on the release rate and
      IR spectra of the controlled-release tablets of SQS-casein were studied,
      respectively. The release rate curve of the controlled-release tablets of SQS
      casein was fitted as zero order, one order and Higuchi equation. The recovery was
      98.59% when the content of SQS in the controlled-release tablets of SQS-casein in
      phosphate buffer solution (pH 6.8) as release media was determined with
      chromogenic reaction of vanillin- sulfuric acid. The release rates are 23.80%,
      51.26% and 94.77% at release times 3, 6 and 12 h, respectively in phosphate
      buffer solution (pH 6.8) as release media. The controlled-release tablets of SQS
      casein release SQS by slowness and constant in 12 h. The chemical bonds are
      formed among SQS, casein and guar gum.

PMID- 22870659
TI  - [The enhancement effect of potassium additives on ICP source radiation].
AB  - In order to improve the quality of inductively coupled plasma-atomic emission
      spectrum and reduce the detection limit of analysis, the influence of potassium
      additives into water samples on water samples' spectral intensity and signal-to
      background ratio was studied. The excitation temperature and electron density of
      plasma were measured through multi-line slope and the Stark broadening method.
      The results demonstrated that the plasma spectral intensity intensity increases
      to a various degree after adding potassium additives into the sample solution.
      When the content of the potassium is 1.0 g x L(-1), the spectral lines intensity
      of element Al, Cr, Cu, Mn, Ni and Zn was increased by 8.62%, 32.29%, 108.45%,
      6.06%, 64.98% and 54.99% respectively, the spectral signal-background ratio
      increased by about 7.90%, 30.95%, 104.60%, 5.21%, 66.00% and 52.82%,
      respectively. Under the conditions of the content of potassium is 1.0 g x L(-1)
      in the sample, the plasma excitation temperature increased by about 239.69 K than
      that without additive, and the electron density increased by about 4.99 x 10(11)
      cm(-3). It is thus clear that potassium additives can improve the quality of
      inductively coupled plasma-atomic emission spectrum.

PMID- 22870660
TI  - [Quantitative analysis of Ba and Sr in soil using laser-induced breakdown
      spectroscopy].
AB  - Laser induced breakdown spectroscopy (LIBS) was applied to measure barium and
      strontium elements in soil. The emission spectrum was emitted as the plasma was
      cooling off, which was collected and analyzed by fiber spectrometer. Spectral
      lines of barium (BaII line at 455.41 nm) and strontium (SrI line at 460.73 nm)
      were separately used for the determining. In order to reduce the error, fitting
      of the spectra by using Lorenizian function was used, the datum was preprocessed
      and the net intensity value of the spectra was collected. A signal intensity in
      the proper range of the characteristic spectrum was chosen as the interior label.
      A calibration curve was drawn according to the ratio between the value of the
      analytical line and the interior scaling line. The correlation coefficient
      between the content and the intensity ratio of Ba and Sr were up to 0.990 0 and
      0.990 6. The content of Ba and Sr was inversed by means of the intensity scaling
      method. As a result, the relative deviations between the content values and the
      standard values of Ba and Sr were 5.7% and 5.1% respectively.

PMID- 22870661
TI  - [Study on microwave digestion of coal for the determination of multi-element by
      ICP-OES and ICP-MS].
AB  - Effects of temperature and four acids (HNO3, HNO3/H2O2, HNO3/HF and
      HNO3/HF+H3BO3) on the coal decomposition by microwave digestion and the multi
      element analysis were studied. SARM20 was used as a coal standard reference
      material. The contents of 10 mineral elements (Al, Ca, Fe, Mg, K, Na, S, Si, Sr
      and Ti) in the coal SARM20 were determined by inductively coupled plasma-optical
      emission spectrometry (ICP-OES). And the contents of 20 heavy metals (Li, Be, Sc,
      V, Cr, Mn, Co, Ni, Cu, Zn, Ga, As, Se, Zr, Sn, Cs, Ba, Ce, Eu and Pb) were
      determined by inductively coupled plasma-mass spectrometry (ICP-MS). The results
      showed that the coal was completely decomposed by microwave digestion with
      HNO3/HF+ H3BO3 at 210 degrees C. Good recoveries for all elements in the coal
      SARM20 were obtained by this two-step microwave digestion method. The recoveries
      of the 10 mineral elements were from 87.5% to 98.8%, and the recoveries of the 20
      heavy metals were from 85% to 112.5%. All RSDs of tests were below 3%.

PMID- 22870662
TI  - [Determination of lithium and strontium at high concentration by ICP-AES].
AB  - The concentrations of lithium and strontium of highly concentrated lithium
      strontium mixed solution were determined simultaneously by inductively coupled
      plasma-atomic emission spectroscopy (ICP-AES). After considering total salinity,
      relation coefficient and intensity at different wavelengths of lithium and
      strontium respectively, the determination wavelength was chosen for lithium and
      strontium separately. Using the determined wavelength, the result varies in terms
      of acid effect, equipment operating parameters and total salinity in the mixed
      solution. When the total salinity was in the range of 0.20%-0.60%, the linear
      correlation coefficient of Li and Sr was better than 0.999 9. After optimizing
      the instrument parameters, the standard solutions relative errors were within
      +0.59%-0.66%, and the samples recoveries were within 99.14%-100.4%. This method
      is reliable due to stability and good recurrence. It can be used to determine
      high concentration of lithium and strontium ions in the lithium-strontium mixed
      solution accurately and rapidly.

PMID- 22870663
TI  - [The chemical and structural analysis of Tibetan medicine Zhuxi].
AB  - Zhuxi is a mineral medicine widely used in traditional Tibetan medicine
      throughout history. However, the bioactive component in Zhuxi still remains
      unclear. In order to enunciate the material basis of its pharmacological
      activity, the present research has determined the chemical component and
      structure of Zhuxi. X-ray fluorescence spectroscopy (XRF), inductively coupled
      plasma optical emission spectrometer (ICP-OES) and X-ray diffraction (XRD) were
      utilized to assay two samples of Zhuxi. XRF and ICP-OES analysis indicated that
      the main elements in Zhuxi are Fe, S and O, also containing some minor elements,
      such as Si, Na, Mg, Al, K, Ni, Ca, Ti and so on. XRD analysis suggested that the
      main crystal compound in Zhuxi is FeS2 (Cubic, Pa-3), also existing a few of
      Fe(+3)O(OH) (orthorhombic, Pbnm) and other some unknown compounds. These studies
      has highlighted the potential the element components and compound structures of
      Zhuxi, so it may be a good starting point for exploring the material basis of its
      pharmacological activity.

PMID- 22870664
TI  - [Detection of trace elements in the sediment of Lop Nur samples by ICP-MS].
AB  - Twenty eight trace elements in the sediment of Lop Nur in different latitude and
      longitude were tested by ICP-MS. The results showed that the metal contents in
      the soil profile followed a growing trend from the surface to the bottom. And the
      essential element P for living body in each sample was very low, and was the
      lowest on the surface, while was matched in the other four layers. The results
      will help to understand the ecosystem evolution of Lop Nur drying up after the
      sediment deposition.

PMID- 22870665
TI  - [Study on the adsorption behavior of beads of maleic anhydride-co-styrene to
      Pb(II) by FAAS].
AB  - The crosslinked polymer beads was synthesized by free emulsion polymerization
      using maleic anhydride and styrene. The chemical structure and morphology of the
      polymer beads were analyzed using FTIR and SEM. And the dynamic adsorption
      properties of beads for Pb(II) was studied by atomic adsorption
      spectrometry(AAS). The relevant factors influencing adsorption and desorption
      were investigated. The results showed that in the solution at pH 5, when the
      sample flow rate was 1.0 mL x min(-1), the adsorption rate of Pb(II) reached more
      than 95%. Using 1 moL x L(-1) nitrate acid as the best eluant the absorbates were
      desorbed at the flow rate of 0.5 mL x min(-1), the recovery of Pb(II) reached
      more than 99%. Under the optimum conditions, the adsorption capacity could be up
      to 26.5 mg x g(-1), the detection limits(3sigma11) were 2.1 microg x L(-1) and
      relative standard deviation (RSD) was 2.5%. The method has been applied to the
      determination of trace lead in water samples with satisfactory results.

PMID- 22870666
TI  - [Rapid determination of silicon content in black liquor of straw fibrous
      material].
AB  - The present paper reports a novel method for the determination of silicon content
      in straw fibrous material black liquor based on alpha-Si--Mo heteropoly acid
      spectrophotometry. The selected conditions were as follows: detection wavelength
      360 nm, pH 4.0, and reaction time 10 min. It was found that the acidic soluble
      lignin in the sample liquor was the major interference species in the silicon
      content determination. The interference of acidic soluble lignin can be
      eliminated by hydrogen peroxide-nitric acid digestion method. The present method
      is not only simple, rapid, stable and less interferential, but also of good
      measurement precision and accuracy, with the relative standard deviations of
      0.9%, and recoveries of 99.0%-102%. It is suitable for use in high silicon
      content of black liquor routine rapid analyses.

PMID- 22870667
TI  - [Distribution of lignin in Chinese fir branches determined by ultraviolet
      microspectrometer].
AB  - Distribution of lignin in the cell walls of Chinese fir branches emerged in the
      spring season were first studied by using ultraviolet microscope based on their
      cell microstructure observation and lignin qualitative measurement by the
      lightmicroscope and confocal laser scanning microscope. The results showed that
      the contents of lignin are inhomogeneously distributed in different micro-areas
      of the cell walls. The order of lignin concentrations is the cell corner>the
      middle lamellar>the secondary with the absorbance values of ultraviolet wave of
      0.489, 0.307 and 0.278, respectively. The result of quantitative analysis
      consists with that of qualitative analysis. A new measurement method was proposed
      to study the distribution of lignin content in wood cell walls in CFhina.

PMID- 22870668
TI  - [A new automated method to identify emission line star from massive spectra].
AB  - Stellar spectra are characterized by obvious absorption lines or absorption
      bands, while those with emission lines are usually special stars such as
      cataclysmic variable stars (CVs), HerbigAe/Be etc. The further study of this kind
      of spectra is meaningful. The present paper proposed a new method to identify
      emission line stars (ELS) spectra automatically. After the continuum
      normalization is done for the original spectral flux, line detection is made by
      comparing the normalized flux with the mean and standard deviation of the flux in
      its neighbor region The results of the experiment on massive spectra from SDSS
      DR8 indicate that the method can identify ELS spectra completely and accurately.
      Since no complex transformation and computation are involved in this method, the
      identifying process is fast and it is ideal for the ELS detection in large sky
      survey projects like LAMOST and SDSS.

PMID- 22870669
TI  - [Study on spectrum inversion of spatially modulated Fourier transform
      spectrometer].
AB  - The sampling mode of static Fourier transform spectrometer is spatial domain
      sampling. The interferogram function is sampled by two orthogonal stepped mirrors
      and the interference irradiance is received by the detector. The interferogram
      image is a planar spatial array which consists of MXM interferogram units. After
      image segmentation, the interferogram image is divided into M x M interferogram
      units according to comparability criterion. By means of addressing location, the
      sampled interferogram sequence which matches up to the discrete optical path
      difference sequence could be gained. Using over-zero sampling technique, the big
      single side interferogram sequence and the small double side interferogram
      sequence are apodizated by different window functions. For the sake of correcting
      phase error, the frequency-domain spectrum correction and space-domain
      interferogram correction are researched and improved. The simulation result shows
      that the two methods can both gain the perfect spectrum line shape, and the
      effect of space-domain interferogram correction is better than others with the
      spectrum standard deviation only 0.012 088.

PMID- 22870670
TI  - [Application of ADV212 to the large field of view multi-spectral TDICCD space
      camera].
AB  - In order to resolve the difficult to hardware implementation of the whole vector
      quantization-based, predictive coding-based and transform coding-based
      compression scheme caused by the large volume of data, small spectral redundancy
      and line frequency variability etc. in multi-spectral space camera, an image
      compression scheme based on ADV212 was proposed in space camera. Firstly, custom
      specific mode was presented based on the working principle of adv212 and CCD
      image properties. In the Custom-specific mode, an ADV212 is able to compress 8
      channel CCD data by proposed image frame and interrupt processing strategy using
      pipelining. Then, this paper analyses the two parameters which affect the quality
      of image compression. A (10, 5) setting the quantization step method was
      proposed, This method makes the rate control error reduces 16.385%. Finally, the
      verification experiments to ADV212 compression system using ground test equipment
      were carried out. The experiments results showed that compression system can be
      fast and stable work. All PSNR were more than 30 dB in the compression ratio of
      2:1 to 32:1. Compared with traditional approaches, the proposed method could
      improve the average PSNR by 2.49 dB in the lossy compression mode when the
      compression ratio is 1bpp. They effectively solve the difficult of hardware
      implementation of the whole wavelet-based compression scheme.

PMID- 22870671
TI  - [A wide-field push-broom hyperspectral imager based on curved prism].
AB  - A wide-field pushbroom hyperspectral imager covering short-wavelength infrared
      range is presented, which can be carried by space borne or airborne platform for
      remote sensing, acquiring hyperspectral data cube, and analyzing substance
      compositions and physicochemical properties. Curved prism which simultaneously
      possesses the functions of dispersion and imaging is used as the prismatic
      element, and the combination with Offner relay configuration substantially
      simplifies the design of spectrometer. Compared to conventional dispersive
      spectral imagers, this design is compact, light-weighted, and small-sized, and
      can efficiently correct unavoidable spectral line curve (smile) and spectral band
      (keystone or frown) by prismatic dispersion Compared to grating spectral imagers
      of the same configuration, the energy utilization efficiency of this design is
      much higher. The paraxial aberration theory and imaging characteristics of Offner
      relay configuration is briefly described. The optical layout and image
      evaluations, including spatial and spectral dimensions, are illustrated
      respectively, according to Monte Carlo ray-tracing results of seven principal
      wavelengths.

PMID- 22870672
TI  - [An interferometer design for Fourier transform infrared spectrometer].
AB  - A novel interferometer system based on the combinations of cube-corner reflectors
      and fixed plane mirrors was designed to improve the quality of spectra. It
      consists of a pair of cube corner reflectors, two fixed perpendicular plane
      mirrors and one beam splitter. By analyzing the modulation depth and phase error,
      the tilt and shearing of the cube corner reflectors, the deviation angle of cube
      corner reflector, the tilt of fixed plane mirrors and the deviation angle of two
      fixed plane mirrors were analyzed. It was proved that the tilt and shearing of
      the cube corner reflectors, and the deviation angle of two fixed plane mirrors,
      have no effects on the modulation depth and phase error of this new
      interferometer system, and the effect from the vibration, temperature
      fluctuations and other external environmental factors also can be effectively
      reduced, which can significantly improve the spectral resolution and quality.
      Through some experiments, it was found that the instrument has a simple
      structure, good sealing, high resolution, strong stability and other advantages

PMID- 22870673
TI  - [Design of concave grating for ultraviolet-spectrum].
AB  - Ultraviolet-spectrum technology is a kind of low signal and multianalysis
      technology. For taking full advantage of spectral information and reducing the
      volume of spectrometer, we used high efficiency spectroscopy structure based on
      concave grating. Based on concave grating theory and optic design software ZEMAX,
      a flat field concave grating for ultraviolet spectrophotometer was designed from
      primary structure, which relied on global optimization of the software. The
      contradiction between wide spectrum bound and limited spectrum extension was
      resolved, aberrations were reduced successfully, spectrum information was
      utilized fully, and the optic structure of spectrometer was highly efficient. For
      better preference of this spectrophotometer, after get the structure parameter,
      combine grating fabrication condition with practice working condition, grating
      diffractive theory, holographic optics theory and software PCG rate was used for
      diffraction efficiency design and improve. A paradigm of flat field concave
      grating is given, it works between 190 nm to 410 nm, the diameter of the concave
      grating is 20 mm, and F/# is 0.21. The design result was analyzed and evaluated.
      It was showed that if the slit source, whose width is 50 microm, is used to
      reconstruction, the theoretic resolution capacity is better than 3 nm.

PMID- 22870674
TI  - [A two-dimensional double dispersed hadamard transform spectrometer].
AB  - A kind of two-dimensional hadamard transform spectrometer was developed. A
      grating was used for chromatic dispersion of orders and a prism was used for
      spectral dispersion. Quite different from traditional CCD detection method, a
      digital micromirror device (DMD) was applied for optical modulation, and a simple
      point detector was used as the sensor. Compared with traditional two-dimensional
      spectrometer, it has the advantage of high resolution and signal-noise-ratio,
      which was proved by theoretical calculation and computer simulation.

PMID- 22870675
TI  - [Multidimensional assessment and treatment strategy of knee osteoarthritis].

PMID- 22870676
TI  - [Case-control study on the treatment of pain in patients with knee osteoarthritis
      by Pizhen].
AB  - OBJECTIVE: To evaluate and analyze mechanism of Pizhen for the treatment of pain
      in patients with knee osteoarthritis. METHODS: Eighty-five patients (85 knees)
      were divided into two groups according to random number table method. Among 35
      patients in the experimental group, 6 patients were male and 29 patients were
      female, 1 patient lost follow-up, the average age was (56.65 +/- 4.89) years, and
      the patients were treated with Pizhen. Among 50 patients in the control
      group,there were 6 males and 44 females, the average age was (57.54 +/- 4.91)
      years, and the patients were treated with intra-articular injection with sodium
      hyaluronate. The VAS score and the data of algometer from the most obvious
      tenderness around the knee were used to evaluate the clinical effects. RESULTS:
      There were significant differences of scores in the experimental group before and
      after treatment (P<0.01). There were significant differences of scores in the
      control group before and after treatment (P<0.01). After treatment, there were no
      statistical differences of VAS score and the data of algometer between
      experimental and control groups ( P>0.01). There was negative correlation between
      VAS score and the data of algometer. CONCLUSION: The Pizhen is an effective
      method to treat pain in patients with knee osteoarthritis by relaxing tendon of
      soft tissue around pain point of knee joint, and relaxing compress and
      stimulation of nerves.

PMID- 22870677
TI  - [Study on the diagnostic value of whole-organ magnetic resonance imaging score
      (WORMS) in knee osteoarthritis].
AB  - OBJECTIVE: To explore the diagnostic value of whole-organ magnetic resonance
      imaging score (WORMS) in knee osteoarthritis (KOA). METHODS: From November 2009
      to January 2011,70 patients with KOA combined with knee effusion among outpatient
      and inpatient were analyzed retrospectively. Among the patients, 12 patients were
      male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age
      of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the
      imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were
      measured respectively by ELISA. The correlation analyses and multiple linear
      regression analysis were studied to determine associations among biomarkers,
      clinical variables and radiographic findings of knee joints. RESULTS: The average
      scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45)
      respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml
      respectively. Grouped by less than the lowest quartile and more than the highest
      quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there
      was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively
      correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01;
      respectively); WOMAC was also positively correlated with K-L score (r=0.692,
      P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated
      with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01;
      r=0.917, P<0.01). It was determined by stepwise regression that the KOA was
      mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as
      a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as
      independent variables (F=20.327, P<0.01). CONCLUSION: WORMS has a better
      reference value for diagnosis of KOA. The expression of COMP is high in the
      synovial fluid when WORMS at the high point. The clinical symptoms of knee
      osteoarthritis are mainly affected by WORMS and K-L score.

PMID- 22870678
TI  - [Case-control study on isometric quadriceps femoris contraction exercises for the
      treatment of knee osteoarthritis].
AB  - OBJECTIVE: To evaluate clinical effects of knee osteoarthritis with the treatment
      of the isometric quadriceps femoris contraction exercises, which aims at
      establishing the exercise prescription of knee osteoarthritis,and promoting its
      clinical application. METHODS: From January 2008 to September 2010, 120 patients
      with knee osteoarthritis were divided into two groups according to visiting
      sequence, including 39 males and 81 females, ranging in age from 40 to 85 years,
      with an average of 62.50 years, the disease course ranged from 1 month to 30
      years. There were 60 patients in the therapeutic group, including 21 males and 39
      females, ranging in age from 40 to 85 years, with an average of (62.27 +/- 8.99)
      years, the disease course ranged from 2 months to 30 years; and the patients were
      treated with intra-articular injection of sodium hyaluronate and isometric
      quadriceps femoris contraction exercises for treatment. There were 60 patients in
      the control group; including 18 males and 42 females, ranging in age from 41 to
      80 years, with an average of (62.72 +/- 8.34) years, the disease course ranged
      from 1 month to 30 years; and the patients were treated with conventional intra
      articular injection of sodium hyaluronate. The index such as the pains,functions
      and articular dropsy of the knees were observed and the clinical effects were
      compared respectively. RESULTS: All the patients were followed up, and the
      duration ranged from 1 to 3 years, with an average of 18 months. According to
      standard of JOA about evaluating the therapeutic effects of knee osteoarthritis:
      in the therapeutic group, 12 patients got an excellent result, 33 good, 14 poor
      and 1 bad; and in the control group, 7 patients got an excellent result, 14 good,
      31 poor and 8 bad. The clinical results of therapeutic group was better than that
      of control group. There were 7 recurrent cases in the therapeutic group and 31
      recurrent cases in the control group; the recurrence rate in therapeutic group
      was lower than that of control group. CONCLUSION: The isometric quadriceps
      femoris contraction exercises has obvious effect in alleviating the symptoms,
      improving joint function, strengthening the joint stability and slowing down
      joint degeneration process for the treatment of knee osteoarthritis, which has a
      good effect in the long-term clinical effects.

PMID- 22870680
TI  - [Case-control study of influence factors analysis on short-term recovery after
      total knee arthroplasty in old patients with osteoarehritis].
AB  - OBJECTIVE: To investigate the relationship between variable influence factors and
      postoperative 2 week hospital special surgery (HSS) of knee joint, thus offer the
      treatment suggestion to patients with osteoarthritis, and judge the comprehensive
      effective prognosis to the clinical patient. METHODS: From March 2008 to August
      2010, 72 patients with 72 knees were treated with TKA (treatment group),
      including 30 males and 42 females with a mean age of (71.9 +/- 6.2) years
      (ranged, 60 to 86 years). Twenty-two patients with HoldenIV OA treated by
      arthroscopy were in the control group, including 10 males and 12 females with a
      mean age of (70.5 +/- 5.9) years. The index including height, weight, BMI, muscle
      strength,knee joint HSS score and ROM were evaluated before operation and at 1st,
      2nd weeks after operation. RESULTS: The HSS knee score and ROMs of patients in
      the treatment group improved. The pre-operative ROM, HSS score, knee pain,
      continous passive motion (CPM) at different level (i.e.CPM initial angle) had a
      prominent positive correlation with HSS score in postoperative 2 weeks. The
      factors such as patients' age, height, weight, BMI, muscular strength, etc. had
      no obvious relevant to HSS score in postoperative 2 weeks. CONCLUSION: The pre
      operative HSS score, knee pain, knee ROM, perioperative severe complications, and
      postoperative CPM initial angle have a positive correlation with the
      postoperative effects.

PMID- 22870679
TI  - [Multiple linear regression analysis of X-ray measurement and WOMAC scores of
      knee osteoarthritis].
AB  - OBJECTIVE: To perform Multiple Linear Regression analysis of X-ray measurement
      and WOMAC scores of knee osteoarthritis, and to analyze their relationship with
      clinical and biomechanical concepts. METHODS: From March 2011 to July 2011, 140
      patients (250 knees) were reviewed, including 132 knees in the left and 118 knees
      in the right; ranging in age from 40 to 71 years, with an average of 54.68 years.
      The MB-RULER measurement software was applied to measure femoral angle, tibial
      angle, femorotibial angle, joint gap angle from antero-posterir and lateral
      position of X-rays. The WOMAC scores were also collected. Then multiple
      regression equations was applied for the linear regression analysis of
      correlation between the X-ray measurement and WOMAC scores. RESULTS: There was
      statistical significance in the regression equation of AP X-rays value and WOMAC
      scores (P<0.05), while there was no statistical significance in the regression
      equation of lateral X-ray value and WOMAC scores (P>0.05). CONCLUSION: 1) X-ray
      measurement of knee joint can reflect the WOMAC scores to a certain extent. 2) It
      is necessary to measure the X-ray mechanical axis of knee, which is important for
      diagnosis and treatment of osteoarthritis. 3) The correlation between tibial
      angle,joint gap angle on antero-posterior X-ray and WOMAC scores is significant,
      which can be used to assess the functional recovery of patients before and after
      treatment.

PMID- 22870681
TI  - [Serum levels of cartilage oligomeric matrix protein in the diagnosis of knee
      osteoarthritis].
AB  - OBJECTIVE: To select sub-clinical patients with symptoms of knee osteoarthritis
      (KOA) without X-ray changes by measuring the serum level of cartilage oligomeric
      matrix protein (COMP) with ELISA, so as to diagnose and treat patients with knee
      osteoarthritis at early stage. METHODS: The 115 patients with KOA or with
      symptomatic primary KOA were enrolled from August 2007 to September 2009, which
      was OA group; and 35 healthy people in the control group. In OA group, there were
      55 males and 60 females,ranging in age from 39 to 76 years, with an average of
      (55 +/- 13.32) years; the body mass index (BMI) ranged from 15.1 to 29.8; the
      disease course ranged from 6 to 60 months. In the control group, there were 16
      males and 19 females, ranging in age from 36 to 77 years, with an average of (53
      +/- 12.53) years; the BMI ranged from 14.8 to 29.2. Patients with symptomatic
      primary knee OA of Kellgren-Lawrence (K-L) grade I-IV were evaluated. Serum level
      of COMP and its correlation with OA grade were analyzed by ELISA method. The
      patients were treated with Celecoxib capsules. The patients in OA group were
      followed up, and the duration ranged from 24 to 38 months (averaged, 33.4
      months), and the serum level of COMP were analyzed before and after treatment.
      RESULTS: The serum level of COMP in the control group varied with age (t= 2.50,
      P=0.02). The serum level of COMP did not correlate with gender (control group:
      t=0.98, P=0.34; OA group: t=0.18, P= 0.86), BMI (control group: t=0.56, P=0.92;
      OA group: t=0.17, P=0.85) and smoking (control group: t=1.89, P=0.08; OA group:
      t=0.70, P=0.49). The serum level of COMP was higher in the patients with higher K
      L grades than in the patients with lower K-L grades (F=15.56, P=0.001) . The sub
      clinical KOA patients without X-ray changes can be detected significant higher
      COMP levels than sub-clinical patients with other diseases (t=2.55, P=0.03).
      Therefore, according to this method, subclinical OA patients can be detected from
      people with other sub-clinical diseases successfully. CONCLUSION: The serum level
      of COMP can be used as a potential prognostic marker to diagnose KOA.

PMID- 22870682
TI  - [Pulsed electromagnetic field therapy for the treatment of knee osteoarthritis: a
      systematic review].
AB  - OBJECTIVE: To evaluate the clinical effectiveness of pulsed electromagnetic field
      therapy in the treatment of knee osteoarthritis. METHODS: Based on the principles
      and methods of Cochrane systematic reviews, the authors searched the Cochrane
      Library (2012, 2 issue), PubMed (1966 to February, 2012), EMBASE (1974 to
      February, 2012), Chinese Biomedicine Database (1978 to February, 2012), China
      Journal Full-text Database (1979 to February, 2012), VIP database (1989 to
      February, 2012), as well as search engine Google Scholar. Randomized controlled
      trials (RCTs) of pulsed electromagnetic field therapy to treat knee
      osteoarthritis were included. The authors assessed the quality of the included
      trials according to the Cochrane Handbook for Systematic Reviews of Interventions
      Version. The Cochrane Collaboration's software RevMan 5.1 was used for meta
      analysis. RESULTS: Five RCTs totaling 331 patients were included. The results
      showed that compared with placebo control treatment, pulsed electromagnetic field
      therapy had little clinical benefit in relieving the pain of knee osteoarthritis
      [WMD=0.12, 95%CI (-0.46,0.69)], reducing morning stiffness time [WMD=0.08, 95%CI
      (-0.05, 0.21)] and improving the knee function [WMD=-1.16, 95%CI (-4.36, 2.05)].
      There were no significant differences between the two groups. CONCLUSION: The
      effects of Pulsed electromagnetic field therapy for treating knee osteoarthritis
      need more powerful trails to be confirmed. The above conclusions still need more
      high-quality randomized controlled trails to be verified owing to the limitations
      of the number and the quality of systematic review included studies.

PMID- 22870683
TI  - [Case-control study on influence of femoral neck fracture on deep venous
      thrombosis in patients undergoing prosthetic hip surgery].
AB  - OBJECTIVE: To investigate the association between femoral neck fracture and deep
      vein thrombosis (DVT) in patients undergoing prosthetic hip surgery. METHODS: The
      data of patients who underwent prosthetic hip surgery from January 2005 to July
      2010 were collected, the cases were included into the study after exclusion of
      those could not be suitable for the study. The patients with diagnosis of deep
      vein thrombosis (DVT) were identified together as the case group, and the
      patients without DVT were selected randomly and matched with frequency as the
      control group. The matching characteristics included age, gender and body weight.
      The patients with femoral neck fracture were counted in both case and control
      group. The odds ratio was calculated and the exposure rate of both group were
      compared. RESULTS: There were total 670 patients underwent prosthetic hip surgery
      during the period, and after exclusion,the data of 408 patients were collected
      into the study. There were 13 patients in the case group (4 males and 9 females,
      ranging in age fram 57 to 91 years), all of them suffering from femoral neck
      fracture and the exposure rate was 100.0% (13/13). There were 52 patients in the
      control group (18 males and 34 females, ranging in age from 57 to 91 years), 39
      of them suffering from femoral neck fracture, the exposure rate was 75.0%
      (39/52); there was no statistically significant difference in exposure rate of
      two groups. CONCLUSION: The diagnosis of femoral neck fracture is not the
      independent risk factor for postoperative DVT of prosthetic hip surgery. The
      epidemiologic characteristics of femoral neck fracture indicate that the patients
      are in high risk of DVT, who meanwhile are the most of patients undergoing the
      prosthetic hip surgery. Though the surgery itself is a risk of DVT, it can reduce
      the risks for patients with femoral neck fracture through some therapeutic
      effects.

PMID- 22870684
TI  - [Case-control study on cable-pin system in the treatment of olecranon fractures].
AB  - OBJECTIVE: To prospectively evaluate the clinical result of Cable-Pin system in
      the treatment of olecranon fractures and compare with tension band wiring (TBW)
      method. METHODS: From March 2008 to June 2010,65 patients with olecranon
      fractures were divided into two groups: 32 patients in Cable-Pin group were
      treated with Cable-Pin system, including 18 males and 14 females, ranging in age
      from 21 to 69 years, with an average of (53.69 +/- 13.42) years; 33 patients in
      TBW group were treated with Kirschner tension bend, including 20 males and 13
      females, ranging in age from 20 to 70 years, with an average of (53.18 +/- 13.36)
      years. The incision length, operation time, the amounts of hemoglobin after
      operation, fracture healing time, complications and HSS elbow scores were
      recorded and analyzed statistically. The follow-up period ranged from 12 to 24
      months, with an average period of 18.4 months. RESULTS: There were statistical
      differences (P<0.05) in fracture healing time (t= 2.588, P=0.012), complication
      rate (chi2=4.534, P=0.033) and HSS elbow joint scores (Z=-2.039, P=0.041) between
      two groups, which all were superior to TBW in Cable-Pin group. There was no
      statistical differences (P>0.05) in the length of incision (t= 0.416, P=0.679),
      operation time (t=0.816, P=0.417) and the postoperative amounts of hemoglobin (t=
      0.553, P=0.294) between two groups. CONCLUSION: Cable-Pin system is an easy and
      reliable method for the treatment of olecranon fractures with less complications
      and better functions than TBW.

PMID- 22870685
TI  - [Measurement of diameter of T4 pedicle-rib compomers].
AB  - OBJECTIVE: To measure the diameter of T4 pedicle-rib compomers in normal human
      spines and discuss the importance of related dates. METHODS: T4 computerized
      tomography (CT) images,including two-dimensional,three-dimensional
      reconstruction, of 12 random adult patients were harvested. There were 7 males
      and 5 females with a mean age of 23 years (ranged, 19 to 28 years). The patients
      were divided into groups by self control,which means the diameter of pedicle
      compared with that of pedicle-rib unit in the same side of each T4. The facility
      was GE light speed 16. Measurement of the body specimens from T3 to T5 . The
      parameter included the width of pedicle-rib unit compared with pedicle,the
      longitudinal diameter of pedicle-rib unit compared with pedicle, especially for
      the pedicle-rib overlap. RESULTS: The relationship of T4 pedicle and rib were not
      on the same level but overlapping. The width of pedicle-rib unit was
      significantly larger than that of pedicle (P<0.05). The longitudinal diameters of
      pedicle-rib unit or pedicle were significantly larger than those of pedicle-rib
      overlap (P<0.05); while there was no significantly difference between the pedicle
      rib unit and pedicle (P>0.05). CONCLUSION: The overlapping relationship of T4
      pedicle and rib is partly but not whole, which means the longitudinal diameter of
      T4 pedicle-rib overlap should not be considered as the same of unit or pedicle.

PMID- 22870686
TI  - [Surgical treatment for acute posterolateral structures injuries of the knee
      joint in 12 patients].
AB  - OBJECTIVE: To investigate the clinical results of surgical treatment for acute
      posterolateral structures(PLS) injuries of knee joint. METHODS: Twelve patients
      (12 knees) with acute PLS injuries were treated from May 2006 to October 2008,
      including 9 males and 3 females, ranging in age from 23 to 47 years, with an
      average of 31 years. Nine patients had posterior cruciate ligament (PCL)
      injuries, 3 patients had both anterior cruciate ligament (ACL) and PCL injuries,
      and 7 patients had articular capsule injuries. The knee joint was explored under
      arthroscope and the meniscuses were repaired firstly, then the ACL was rebuilt,
      as well as the PCL and PLS at the same time. The popliteus muscle tendon
      unit(PMTU) and the lateral collateral ligament (LCL) were anatomy reconstructed
      using variant tendon according to the degree of injury. The cruciate ligament
      reconstructed and fixed after the PLS reconstruction. The capsule tears were
      treated by reinforced suture techniques in the end. IKDC and Lysholm score were
      used to evaluate the postoperative knee joint function. RESULTS: All the patients
      were followed up, and the duration ranged from 12 to 24 months,with an average of
      (16.5 +/- 3.2) months. According to IKDC standard, 8 cases restored to normal
      (grade A), 3 cases near to normal(grade B) and 1 poor (grade C). The preoperative
      Lysholm joint function score was (39.6 +/- 3.1) and improved to (85.1 +/- 2.2)
      after surgery. All the patients were satisfied with their operation because of no
      swelling and no-pain of the knee joint. CONCLUSION: The acute PLS injuries should
      be repaired with anatomy reconstruction of the PMTU and LCL which were the most
      important structure of the PLS. The operative procedure required accurate
      establishment of the bone tunnel, protection of fibular nerve, and avoiding the
      incision of the variant tendon, thus can make the PLS more stable after the
      reconstruction.

PMID- 22870687
TI  - [Clinical effects of surgical vs manual reduction of ankle fractures].
AB  - OBJECTIVE: To investigate the clinical effects of surgical vs manual reduction of
      ankle fractures. METHODS: From March 2006 to April 2010,301 patients with ankle
      fractures were analyzed retrospectively, of whom 134 patients were treated by
      manual reduction and plaster fixation, and the other 167 patients underwent
      surgical treatment. In manual reduction group, there were 86 males and 48 females
      with a mean age of (38.2 +/- 15.7) years, involving Weber-Denis A in 55
      cases,Weber-Denis B in 60 cases, and Weber-Denis C in 19 cases. In surgical
      reduction group, there were 115 males and 52 females with a mean age of (39.6 +/-
      11.9) years, involving Weber-Denis A in 59 cases, Weber-Denis B in 52 cases and
      Weber-Denis C in 56 cases. The score of the ankle's symptoms and function was
      calculated according to Mazur,and the difference was analyzed by Chi-squire test.
      RESULTS: Of the 114 patients with Weber-Denis A, 55 patients were in manual
      reduction group, with excellent, good, acceptable and poor results in 18, 20, 11
      and 6 patients respectively vs 26, 25, 6 and 2 in surgical reduction group of 59
      patients. In patients with Weber-Denis B, there were 60 patients in manual
      reduction group, with excellent, good, acceptable and poor results in 20 , 26, 8
      and 6 patients vs 25, 21, 5, and 1 in surgical reduction group of 52 patients.
      There was no significant difference in clinical effects between the two group of
      Weber-Denis A and B. The remaining 75 patients belonged to Weber-Denis C, of whom
      19 patients were in manual reduction group,with excellent, good, acceptable and
      poor results in 2, 3, 7 and 7 patients vs 21, 18, 11 and 6 in surgical reduction
      group of 56 patients. There was no significant difference in clinical effects
      between the two groups of Weber-Denis C (P=0.007). CONCLUSION: The clinical
      effect of surgical reduction group was obviously better than that of manual
      reduction group for Weber-Denis C, and therefore surgical intervention is
      recommended for this type of fracture.

PMID- 22870688
TI  - [Influence of Jiangu decoction on peroxisome proliferator-activated receptor
      (PPAR) in the femoral head of rabbits with steroid-induced femoral head
      necrosis].
AB  - OBJECTIVE: The Jiangu decoction is used in the treatment of steroid-induced
      femoral head necrosis in clinical experiences, which has functions of tonifying
      kidney and activating blood, and invigorating spleen to remove phlegm. The
      decoction is mainly composed of Radix Polygoni Multiflori, Rhizoma alismatis
      Rhizoma Drynariae, haw, medlar, Radix Astragali, radix rehmanniae, angelica,
      Radix Codonopsis, radix salviae miltiorrhizae, Fructus Ligustri Lucidi, licorice,
      pharmaceutical composition. This study was designed to investigate the influence
      of Jiangu decoction on peroxisome proliferator-activated receptor gamma
      (PPARgamma) in the femoral head of rabbits with steroid-induced femoral head
      necrosis. METHODS: Eighteen adult SPF healthy New Zealand rabbits were divided
      into 3 groups: control group, model group, Jiangu decoction group. The rabbits of
      Jiangu decoction group orally received Jiangu decoction suspension with a dose of
      10 ml/kg each day and the drug content was 0.719 g/ml. The rabbits in control and
      model groups were given saline with a dose of 10 ml/kg. The methylprednisolone
      sodium succinate was injected intramuscularly into left leg with a dose of 40
      mg/kg. Then the rabbits were fed continuously for 3 weeks. The glucocorticoid
      levels, PPARgamma and plasma glucocorticoid levels in the femoral head were
      measured before and after modeling. RESULTS: Before model established, the plasma
      glucocorticoid levels had no significant difference among three groups (P=0.301).
      At 3 weeks after model established,the plasma glucocorticoid level of rabbits in
      model group increased compared to the control group (P=0.001); and the plasma
      glucocorticoid level of rabbits in Jiangu decoction group decreased compared with
      model group (P=0.001). The glucocorticoid level in the local femoral head of
      rabbits in model group increased compared to the control group (P=0.001); and the
      glucocorticoid level in the local femoral head of rabbits in Jiangu decoction
      group decreased compared with model group (P=0.001). The PPARgamma level in the
      local femoral head of rabbits in model group increased compared to the control
      group (P=0.018);and the PPARgamma level in the local femoral head of rabbits in
      Jiangu decoction group decreased compared with model group (P=0.033). CONCLUSION:
      The Jiangu decoction is effective to inhibit the femoral head adipogenic
      differentiation by decrease the PPAR content, so as to prevent and treat steroid
      induced femoral head necrosis.

PMID- 22870689
TI  - [Treatment of knee osteoarthritis with manipulation].

PMID- 22870690
TI  - [Diagnostic value of MRI and MR arthrography in the detection of injuries of
      anterior labrum in shoulder].
AB  - OBJECTIVE: To investigate the diagnostic value of MRI and MR arthrography in the
      detection of injuries of anterior labrum in shoulder and to evaluate the accuracy
      of MR arthrography in the classification of anterior labrum lesion. METHODS:
      Seventy-eight patients with arthroscopically proved anterior labrum lesions(study
      group) and 75 patients with arthroscopically proved intact anterior labrum
      (control group) from January 2007 to December 2010 were included to the study.
      All patients underwent MRI and MR arthrography at our institution prior to
      shoulder arthroscopy. All MRI and MR arthrography were analyzed by one
      musculoskeletal radiologists and one sports medicine surgeon who had no knowledge
      of the clinical histories and arthroscopic results. The same classification
      system of labrum lesions based on arthroscopy was used in image analysis. Imaging
      findings and arthroscopic findings were compared in all patients. With
      arthroscopy used as the standard of reference, the sensitivities, specificities
      and accuracies of MRI and MR arthrography in the detection of anterior labrum
      lesions were compared, and the sensitivities, specificities and accuracies of MR
      arthrography in the correct classification of anterior labrum lesions were
      calculated. RESULTS: In arthroscopy, 78 anterior labrum lesions, 67 rotator cuff
      lesions and 8 SLAP lesions were diagnosed, for the detection of anterior labrum
      lesions, the sensitivity of MRI and MR arthrography was 80.8% and 92.3%,the
      specificity was 89.3% and 97.3%,the accuracy was 85.0% and 94.8% respectively.
      Seventy-eight patients with arthroscopically proved anterior labrum lesions
      included 39 Bankart lesions, 32 ALPSA lesions and 7 Perthes lesions, with MR
      arthrography, Bankart, ALPSA, and Perthes lesions were correctly classified in
      84.6%, 84.4%, and 57.1% of cases, respectively. CONCLUSION: MR arthrography has a
      higher sensitivity, specificity and accuracy than MRI in the detection of
      anterior labrum injuries. MR arthrography was useful in the classification of
      different variants of anterior labrum injuries before operations. It may directly
      influence the surgeon's strategy and is useful in preoperative planning of
      arthroscopic reconstructions.

PMID- 22870691
TI  - [Effects of Pilose antler polypeptide on apoptosis of chondrocyte and related
      cytokines in experimental knee osteoarthritis].
AB  - OBJECTIVE: To explore the effects of Pilose antler polypeptide on apoptosis of
      chondrocyte and related cytokines in experimental knee osteoarthritis. METHODS:
      Totally 64 New Zealand White rabbits of 6 months old were randomly divided into 2
      groups:normal group(n=8)and model group (n=56). Model group was surgically
      induced into knee osteoarthritis model by method of Hulth. After successful
      modeling,the rabbits of model group were further divided into 2 groups: Pilose
      antler polypeptide-treatment group (n=24) and control group (n=24). Pilose antler
      polypeptide-treatment group received 0.5 ml intraarticular injection of Pilose
      antler polypeptide dilution liquid once per 2 days for 30 days while control
      group received 0.5 ml intra-articular injection of physiological saline. On days
      7, 15 and 30 after intervention, articular cartilage samples and synovial fluid
      were collected respectively. The morphological changes of articular cartilage
      under optical microscope and the structural change of chondrocyte were observed
      by transmission electron microscopy. The levels of interleukin-1beta and tumor
      necrosis factor-alpha in synovial fluid was detected by Enzyme-linked
      Immunosorbent Assay. RESULTS: Along with the extending of time, articular
      cartilage degenerated gradually and chondrocytes apoptosis increased
      significantly. On days 7,15 and 30 after intervention, the chondrocyte apoptosis
      index of the Pilose antler polypeptide-treatment group were (20.30 +/- 1.23),
      (28.60 +/- 2.37), (37.10 +/- 1.82) and those of control group were (31.50 +/-
      2.44), (34.40 +/- 1.77), (42.30 +/- 2.33). There were significant differences
      between them (P<0.05). At the same time, the chondrocyte apoptosis index of the
      Pilose antler polypeptide-treatment group were lower than those of control
      group,which had a statistical significance (P<0.05). On days 7,15 and 30 after
      intervention, the levels of interleukin-1beta in synovia fluid of Pilose antler
      polypeptide-treatment group were (15.81 +/- 1.26), (12.59 +/- 1.42), (9.57 +/-
      0.92) microg/L and the level of tumor necrosis factor-alpha were (48.47 +/-
      2.64), (43.46 +/- 1.33), (40.96 +/- 1.05) microg/L, with statistical
      differences(P<0.05). The levels of interleukin-1beta in synovia fluid of control
      group were (18.92 +/- 1.83), (20.25 +/- 2.76), (22.13 +/- 2.24) microg/L and the
      levels of tumor necrosis factor-alpha were (57.92 +/- 2.12), (60.25 +/- 1.48),
      (63.35 +/- 2.15) microg/L. At the same period,the levels of interleukin-1beta and
      tumor necrosis factor-alpha were lower than those of the control group,which had
      a statistical significance (P<0.05). CONCLUSION: Pilose antler polypeptide can
      inhibit chondrocytes apoptosis, decrease the levels of interleukin-1beta and
      tumor necrosis factor-alpha and delay the degeneration of articular cartilage to
      some extent.

PMID- 22870692
TI  - [Comparison study on knee osteoarthritis in rabbits induced by different
      concentrations of papain].
AB  - OBJECTIVE: To compare the knee osteoarthritis (OA) models in rabbits by different
      concentrations of papain and provide data for exploring pathogenesis and
      treatments of this disease. METHODS: Sixty New Zealand white rabbits were
      randomly divided into four groups of 15 each and given injections into the right
      knee on days 1, 3 and 5 including intra-articular injections of 2%, 5% or 10%
      (w/v) papain and 0.03 mol/L L-cysteine at the dose of 0.1 ml/kg (experimental
      groups). The 0.9% NaCl (w/v) with a dose of 0.1 ml/kg were injected intra
      articularly into the right knees of rabbits in the control group. The rabbits
      were sacrificed at 2, 4, 6 weeks respectively after the initiation of papain
      injection and these OA models were evaluated through recording the width of knee
      joint, performing the morphological observation and histological evaluation of
      articular cartilage and synovium. RESULTS: The degenerative changes were
      demonstrated in knee joints of rabbit in all experimental groups, such as thinner
      articular cartilage, fibrillation and destroyed cartilage matrix, and
      inflammation, proliferation, and degeneration of the synovial tissue. All these
      changes were much worse with increased concentration and prolonged observation
      time. CONCLUSION: Different severity of OA are established through intra
      articular injections of 2%, 5% or 10% papain and 0.03 mol/L L-cysteine at the
      dose of 0.1 ml/kg. These models are of the characters of short period and a good
      reproducibility.

PMID- 22870693
TI  - [Surgical treatment for posterior malleolus in complicated external rotation
      ankle fracture].
AB  - OBJECTIVE: To evaluate the indications, surgical techniques and clinical effects
      of the fixation of posterior malleolus in complicated external rotation ankle
      fractures and illuminate the importance of anatomical reduction and rigid
      internal fixation of posterior malleolar fracture. METHODS: From July 2007 to
      June 2009, 32 patients were treated with open reduction and internal
      fixation,involving 21 males and 11 females with an average age of 36 years old
      (ranged from 19 to 68 years old). According to Lauge-Hansen classification: 13
      cases of pronation-external rotation type (IV), 7 and 12 cases of supination
      external rotation type (III and IV). Postoperative functional exercise and
      regular follow-up were done and outcomes were assessed. RESULTS: All the patients
      were followed up,and the duration ranged from 7 to 20 months,with an average of
      14.5 months. According to Ankle Hindfoot Clinical Rating System of the American
      Orthopaedic Foot & Ankle Society (AOFAS), 23 patients got an excellent result, 7
      good, 2 fair, 0 poor. CONCLUSION: Anatomical reduction and rigid internal
      fixation of posterior malleolar fracture as well as early functional exercise
      have significance in restoring ankle joint function and reducing the incidence of
      traumatic arthritis.

PMID- 22870694
TI  - [Value of magnetic resonance imaging in diagnosis of brucellar spondylitis].
AB  - OBJECTIVE: To study characteristic presentations of Brucellar spondylitis on MRI
      in order to improve the diagnostic level. METHODS: From October 2009 to December
      2010,15 patients with Brucellar spondylitis were evaluated by MRI. They included
      11 males and 4 females ranging in age from 31 to 64 (mean 49) years. The major
      clinical manifestations were different degrees of fatigue,fever and low back
      pain. All patients underwent MRI and treated with antibiotic drugs. RESULTS:
      Brucellar spondylitis was mostly localized at the lumbar spine with obvious bony
      hyperostosis in the vertebral periphery. Most foci were in the edge, anterior and
      middle parts of the vertebral body, with low signals on T1WI and mixed low
      signals on T2WI, and high signals on T2 fat suppression, mostly without
      significant changes in intervertebral space. Paraspinal abscess was observed in 5
      cases. Thirteen cases involved the lumbar vertebrae, 1 case involved the thoracic
      and lumbar vertebrae, and 1 case involved the lumbar and sacral vertebrae. Two
      vertebrae were affected in 14 cases, and 3 vertebrae were affected in 1 case.
      CONCLUSION: MRI can provide imaging clues for diagnosis and differential
      diagnosis of Brucellar spondylitis, and has a high clinical value.

PMID- 22870695
TI  - [Treatment of Hoffa fracture using hollow lag screw].
AB  - OBJECTIVE: To investigate the operation techniques and clinical effects of hollow
      lag screws for the treatment of Hoffa fractures. METHODS: From February 2001 to
      May 2009, 13 patients with Hoffa fractures were treated with hollow lag screws,
      including 8 males and 5 females, ranging in age from 23 to 45 years, with a mean
      age of 34.2 years. Six patients had the fractures on the left, 7 patients on the
      right. According to the Letenneuer type, femur lateral condyle: type I in 3
      cases, type III in 2 cases; femur medial condyle: type I in 3 cases, type II in 2
      cases, type III in 3 cases. According to the type of fracture, hollow lag screws
      were used to treat the fracture with different approach. RESULTS: All the
      patients were followed up, and the duration ranged from 12 to 23 months,with a
      mean of 16.5 months. All the patients had no complications such as popliteal
      artery, tibial nerve or peroneal nerve injuries. According to Letenneur knee
      function score: 10 patients got an excellent result, 3 good. At the half year
      after operation, the X-ray showed all the fractures had bone union. There were no
      hollow lag screw loosening, broken or nonunion. CONCLUSION: The clinical effect
      of hollow lag screw for the treatment of Hoffa fractures is satisfactory. The
      surgical approach and fixation should be determined by the type of fracture, the
      location of the fracture line and the size of fracture fragments.

PMID- 22870696
TI  - [Orthopaedic trauma remediation after clinical misdiagnosis and mistreatment
      (with 3 cases analysis)].

PMID- 22870697
TI  - [Treatment of Colles fractures with shaking manipulation].

PMID- 22870698
TI  - [Manifestation of synovial lesions in osteoarthritis].
AB  - Osteoarthritis is a degenerative joint disease,with the characters of degradation
      of articular cartilage, the formation of the joint marginal osteophyte and
      synovium lesions. Previous studies have focused on the treatment of articular
      cartilage lesions. In recent years, new research in shows synovial inflammation
      plays an important role in OA. Synovium lesions and synovial inflammation-related
      factors induced the degradation and destruction of articular cartilage, and
      promoted the development of osteoarthritis. The role of synovial lesions in
      osteoarthritis is increasingly prominent, and the treatment for synovial lesions
      will become a new target. So this paper reviews the various manifestations of
      synovial in osteoarthritis.

PMID- 22870699
TI  - [Topical timolol in the treatment of periocular superficial infantile
      hemangiomas: a prospective study].
AB  - OBJECTIVE: To investigate the efficacy and side effect of topical beta-blocker
      (Timolol Maleate) in the treatment of periocular hemangioma in a prospective
      study. METHODS: 432 outpatients with infantile hemangioma visited our special
      clinic service in Shanghai Ninth People's Hospital from July 2010 to December
      2011. Among them, 12 superficial periocular lesions were selected in the study.
      Timolol was used topically on the lesion in every 12 hours. Two independent
      special doctors evaluated the results according to the pictures before and after
      four-week application of timolol. RESULTS: Were categorized into four levels:
      continuous growth (the lesion continues to grow), stable (no visible change),
      moderate (0-50% of regression) , perfect (more than 50% of improvement). Result
      of the 12 outpatients, 4 showed perfect result, 2 moderate, 4 stable and 2
      continuous growth. No side effect was observed. CONCLUSIONS: Topical timolol is
      effective and safe in the treatment of superficial periocular infantile
      hemangioma. It could be considered as the first line treatment of proliferative
      superficial hemangioma.

PMID- 22870700
TI  - [The therapeutic effect of propranolol with 1064 nm Nd: YAG laser on
      proliferating hemangioma in body surface].
AB  - OBJECTIVE: To observe the therapeutic effect of propranolol with 1 064 nm Nd:YAG
      laser on proliferating hemangioma in body surface. METHODS: 97 patients with
      proliferating hemangiomas in body surface were randomly assigned to three groups:
      A group (32 patients were treated by propranolol with 1064 nm Nd:YAG laser), B
      group (35 patients were treated by 1064 nm Nd:YAG laser), C group (30 patients
      were treated by propranolol). Their visual analog scores, clinical outcomes and
      adverse events were compared respectively. RESULTS: 18 weeks later, A group had a
      mean visual analog score of 65.50 +/- 16.55, compared with 54.03 +/- 20.13 in B
      group, 28.08 +/- 30.34 in C group (P < 0.05); 24 weeks later, the mean visual
      analog scores of three groups were 76.88 +/- 19.05, 63.89 +/- 19.43 and 45.48 +/-
      31.86 (P < 0.05). After 24 weeks' treatment, 9 cases (28.1%) in A group, 3 cases
      (8.6%) in B group, 1 cases (4.0%) in C group obtained complete healing (P <
      0.05). To effect of adverse events in body surface, the mean score of B group was
      higher than the scores of A group and C group (P < 0.05). CONCLUSIONS:
      Propranolol with 1064 nm Nd:YAG laser is effective and safe in the treatment of
      proliferating hemangioma.

PMID- 22870701
TI  - [Combined injection of pingyangmycin & dexamethasone for the treatment of
      maxillofacial and cervical venous malformations].
AB  - OBJECTIVE: To investigate the therapeutic effect of combined injection of
      pingyangmycin (PYM) & dexame thasone (DXM) for the treatment of maxillofacial and
      cervical venous malformations. METHODS: From August 1995 to October 2008, 116
      cases with maxillofacial and cervical venous malformations were retrospectively
      analyzed. The injection dilute was made with PYM 8 mg, DXM 10 mg and 2% lidocaine
      2.0 ml (PYM 2 mg/ml). The PYM diluent 1.0-4.0 ml (including the PYM 2-8 mg) was
      injected into the tumor according to the patients age, tumor size and location.
      For children, PYM 2-4 mg was injected for one treatment. The needle should be
      inserted into tumor perpendicularly or from the edge of tumor. After withdrawing
      blood, the drug was injected into the tumor slowly. The injection could be
      repeated every 7-10 days. The clinical signs were recorded; ultrasonography and
      chest X-ray were performed to evaluate the therapeutic effect. RESULTS: 1-5
      treatments of injection were performed in the 116 patients. The tumor shrinked
      and disappeared after treatment with PYM 2-40 mg and DXM 5-50 mg. The patients
      were followed up for 3-5 years with no occurrence and complication. CONCLUSIONS:
      It's safe, effective and practical to treat maxillofacial and cervical venous
      malformations by combined injection of PYM and DXM. The cosmetic appearance and
      function can be preserved at the most.

PMID- 22870702
TI  - [Penile augmentation and elongation using autologous dermal-fat strip grafting].
AB  - OBJECTIVE: To investigate the effect of autologous dermal-fat strip grafting in
      penile augmentation and elongation. METHODS: From May 2004 to December 2010, 24
      patients underwent penile enhancement with free dermal-fat strip grafting.
      Through suprapubic incision, the superior suspensory ligament and part deep
      suspensory ligament are cutted off to lengthen the penis. The resulted dead space
      is filled with the autologous dermal-fat strip (6.0-9.5 cm in length, 1.2-1.5 cm
      in width and 0.6-0.8 cm in depth) to enhance the penis. RESULTS: Primary healing
      was achieved in 23 cases. Incisional fat liquefaction happened in one case which
      healed after dressing change. The penile appearance was satisfactory both at rest
      or erection. The penile length and circumference increased by 2.5-4.8 cm
      (average, 3.2 cm) and 1.8-3.0 cm (average, 2.4 cm), respectively. 18 patients
      were followed up for 3 months to 5 years. All the patients were satisfactory on
      the cosmetic and functional results. No complication happened. CONCLUSIONS: It is
      safe and effective for penile augmention and elongation with autologous dermal
      fat strip grafting and disconnection of penile suspensory ligament.

PMID- 22870703
TI  - [Scalp flaps pedicled with superficial temporal vessel and hair removal for
      reconstruction of facial skin defects].
AB  - OBJECTIVE: To investigate the therapeutic effect of scalp flaps pedicled with
      superficial temporal vessel and hair removal for reconstruction of facial skin
      defects. METHODS: From Jan. 2010 to Dec. 2011, 6 cases with large facial skin
      defects were treated with scalp flaps pedicled with superficial temporal vessel
      and hair removal. At the first stage, the skin expanders were implanted
      subcutaneously at the homolateral side according to the defect size. After the
      expansion was finished, the expanded flaps pedicled with superficial temporal
      vessel were used to reconstruct the facial skin defects at the second stage. 2
      weeks after operation, hair removal was performed to remove the hair on flaps. 4
      6 treatments were needed. RESULTS: Seven flaps in 6 cases were survived
      completely. The wounds at donor sites were closed directly. The effect of hair
      removal was reliable. The patients were followed up for 6 months to 1 year. The
      flap color, texture and thickness had a good match with surrounding skin tissue.
      CONCLUSIONS: It is a good option to reconstruct facial skin defects with scalp
      flaps pedicled with superficial temporal vessel and hair removal.

PMID- 22870704
TI  - [Application of slender narrow pedicle flap in facial skin cancer treatment].
AB  - OBJECTIVE: To introduce the application of slender narrow pedicle flap in
      repairing facial tissue defects after skin carcinoma excision, and investigate
      its survival mechanism. METHODS: The slender narrow pedicle iateral
      maxillocevical flap was designed with its pedicle including skin fascia or only
      the fascia located in front of auricle or behind of it, repaired 26 cases of
      facial defects, including 5 temporal skin basal cell carcinoma, 6 skin squamous
      cell carcinoma, and 1 facial skin malignant melanoma, 8 skin basal cell
      carcinoma, 5 skin squamous cell carcinoma, 1 skin mucinous carcinoma. In 26
      cases, 24 cases their pedicles in front of the auricle, 2 cases behind of the
      auricle; 4 cases their pedicles only including fascia. The size of the flaps
      ranged from 3.0 cm x 2.5 cm to 10.0 cm x 8.0 cm. The width and length of the
      pedicle ranged 1.0-1.5 cm and 2-6 cm. RESULTS: 26 cases of the slender narrow
      pedicle flaps all survived and the results were satisfactory except 5 cases of
      distal congestion, then gradual recovery. CONCLUSIONS: This slender narrow flap
      don't include any major blood vessel, without dissecting the blood vessels in
      operating. Due to its slender pedicle, the whole flap looks like "pingpang bat",
      the flap rotation is easy and its coverage area is very large, without cat ears.
      The postoperative appearance (color, texture, cosmetic aspect) is satisfactory.
      This slender narrow flap is an extraordinary new flap design and is ideal for the
      repair of the facial tissue defect after skin carcinoma excision.

PMID- 22870705
TI  - [Skin needle roller importing triamcinolone acetonide into scar to treat
      hypertrophic scars].
AB  - OBJECTIVE: To evaluate the effect of importing triamcinolone acetonide into
      hypertrophic scars with skin roller needles. METHODS: Thirty-two cases with burn
      hypertrophic scar were treated. The skin roller needles were moved back and forth
      on the hypertrophic scars with triamcinolone acetonide dropping on the scar
      surface at the same time. So the triamcinolone acetonide could be imported into
      the scar through needles and needle holes. The effect was evaluated as cured,
      effective, and no effect. The Vancouver scaring criteria and visual analogue
      scale was used to assess the scar color, thickness, texture and feeling before
      and after treatment, as well as at the untreated scar area (control). RESULTS:
      Thirty-two cases were treated 1-3 times, including 28 cases with cured result and
      4 cases with effective result. The total effective rate was 100%. The scar color,
      thickness, texture and feeling was significantly different between the scar
      before and after treatment, or between the treated and untreated scar (P < 0.05).
      CONCLUSIONS: Importing triamcinolone acetonide into hypertrophic scars with skin
      roller needles is effective. It is a new method for the treatment of large
      hypertrophic scar with medicine.

PMID- 22870706
TI  - [Reconstruction of combined skin and bilateral artey defects at palmar side of
      fingers by free posterior interrosseous artery flap in a bridge fashion].
AB  - OBJECTIVE: To investigate the feasibility and therapeutic effect of free
      posterior interrosseous artery flap in a bridge fashion for combined skin and
      bilateral artery defects at palmar side of fingers. METHODS: 6 cases with
      combined skin and bilateral artery defects at palmar side of fingers were treated
      with long-pedicled free posterior interrosseous artery flap in a bridge fashion.
      The flap size ranged from 3.5 cm x 2.0 cm to 6.5 em x 3.0 cm. The wounds at donor
      sites were closed directly. RESULTS: All the 6 flaps survived completely without
      any complication, and the wounds healed primarily. The blood supply and vein
      drainage in all the 6 fingers were normal. 4 cases were followed up for 1-12
      months (average, 7 months). Satisfactory cosmetic and functional results were
      achieved. The flaps looked a little bit thicker than the surrounding tissue.
      CONCLUSIONS: The long-pedicled free posterior interrosseous artery flap in a
      bridge fashion is a good option for reconstruction of the combined skin and
      bilateral artery defects at palmar side of fingers in one stage.

PMID- 22870707
TI  - [Experimental research on DNA methylation profile in congenital microtia].
AB  - OBJECTIVE: To screen for abnormal methylation in CpG islands and CpG sites
      through whole genome of congenital microtia to identify their associated genes.
      To discuss the relationship between abnormal methylation level of genes and the
      etiology of congenital microtia. METHODS: Residual ear cartilage of 50 patients
      with microtia was collected with ear cartilage of 34 patients without ear
      malformations as control. Nimblegen CpG promoter array was chosen to screen the
      28,226 CpG islands in the whole genome of both experimental and control groups.
      The genes with differential methylated CpG islands were selected. SpectroCHIP
      array was chosen to detect the methylation level of each CpG site in abnormal
      methyletion CpG islands of both experimental and control groups. The CpG sites
      with differential methylation level were selected. RESULTS: There were 36 CpG
      islands with differential methylated level in whole genome between experimental
      group and control group, among which 29 CpG islands were connected with 29 named
      genes. In the abnormal methylated CpG islands of COL18A1, MYH14, RBMY1A1 and
      ZIC3, 6 differentially methylated CpG sites were found with statistical
      significance. The methylation level of these 6 CpG sites in experimental group
      and control group were COL18A1_2_CpG_170.9783 +/- 0.0235 and 0.9526 +/- 0.0589;
      MYH14_CpG_170.9600 +/- 0.0414 and 0.9284 +/- 0.0655; RBMY1A1_1_CpG_3.40.9966 +/-
      0.0055 and 0.9914 +/- 0.0069; RBMY1A1_1_CpG_130.9648 +/- 0.0118 and 0.9757 +/-
      0.0127; ZIC3_3_CpG_150.0867 +/- 0.0212 and 0.0543 +/- 0.0399; ZIC3_2_CpG_270.3775
      +/- 0.1816 and 0.472 3 +/- 0.0439. CONCLUSIONS: The DNA methylation profile of
      the entire genome is initially established. The abnormal methylated CpG islands
      of COL18A1, MYH14, RBMY1A1 and ZIC3 might be related to the pathogenesis of
      microtia.

PMID- 22870708
TI  - [Experiment study of SDF-1 expression during the survival process of the narrow
      pedicle flap with hypoxia and ischemia].
AB  - OBJECTIVE: To detect the stromal cell derived factor 1 (SDF-1) expression during
      the survival process of the narrow pedicle flap with hypoxia and ischemia and to
      investigate the role of SDF-1/ CXCR4 axis in flap neovascularization. METHODS:
      The narrow pedicle flaps were formed on the bilateral back of 5 pigs. The pedicle
      ratio of length to width was 4:2. The flap size was 2 cm x 2 cm (group A), 3 cm x
      3 cm (group B), 4 cm x 4 cm (group C), 5 cm x 5 cm(group D), 6 cm x6 cm (group
      E). The flaps survival rate was observed and HE staining was performed. The SDF-1
      expression at the distal end of flaps was detected by ELISA during the operation
      and 3, 5, 7, 14 days after operation. RESULTS: (1) SDF-1 expression at the same
      group increased after operation until it reached the peak value at 5 days after
      operation; then it decreased to basic value. (2) SDF-1 expression in different
      groups was higher in bigger flaps until the flaps size reached 5 cm x 5 cm. Then
      partial necrosis happened at the distal end of flaps. CONCLUSIONS: The SDF-1
      expression may be related to the blood supply during the survival process of the
      narrow pedicle flap with hypoxia and ischemia.

PMID- 22870709
TI  - [Treat flap ischemia-reperfusion injury by local transplanting human umbilical
      cord mesenchymal stem cells].
AB  - OBJECTIVE: To explore the possibilities of human umbilical cord mesenchymal stem
      cells (HUC-MSCs) differentiate into vascular endothelial cells, thus to treat
      flap ischemic reperfusion injury and then promote the flap survival. METHODS: HUC
      MSCs in vitro, and flow cytometric identification. Labeling stem cells with EdU,
      and then transplant stem cells into local of ischemia-reperfusion injury flap of
      rats (treatment group) , setting PBS control group. Observe the flap survival
      rate 7 days after, and execute rats. Take flap tissues for pathological sections,
      and detect vascular endothelial growth factor (VEGF) by immunohistochemical
      staining, detect the distribution or differentiation of the donor cells in cell
      receptor by EdU fluorescent staining. RESULTS: 7 days after, the flap survival
      rate of treatment group was (97.58 +/- 3.41)%, the flap survival rate of control
      group was (54.37 +/- 8.78)%, the rate of treatment group was higher than control
      group (P < 0.05). The density of micrangium and VEGF of treatment group was
      higher than control group obviously (P < 0.05). The continuous distribution of
      positive cells that labeled with EdU were found in new vascular endothelial of
      treatment group' s survival flap tissues. CONCLUSIONS: HUC-MSCs could
      differentiate into vascular endothelial cells, directly involved in generating
      new blood vesselsand, additionally could increase expression of VEGF to promote
      the formation of new blood vessels, then to set up the new micro circulation,
      accordingly to treat flap ischemic reperfusion injury and then promote the flap
      survival.

PMID- 22870710
TI  - [Implantation of newborn mice skin cells with chamber method to construct a model
      of hair follicle development].
AB  - OBJECTIVE: To construct a convenient, reliable and visual model of hair follicle
      development to test the hair-inductive potential of follicular cells and
      investigate the molecular mechanism regulating hair follicle morphogenesis and
      cycling. METHODS: An open chamber was transplanted into the nude mice dorsal
      skin, dermal and epidermal cells isolated from newborn C57BL/6 mice skin were
      mixed at a specific ratio and then injected into the chamber together, 1 week
      after transplantation, the chamber was removed, and then, hair formation and
      regeneration after hair plucking was observed. RESULTS: 1 week after cells
      implantation, the wound was moist without apparent contraction and among that
      pink and translucent tissue was formed. 2 weeks after implantation, the wound
      healed completely. 3 weeks after implantation, black hair grew from the skin was
      observed. 4 weeks after implantation, thick and black hair grew from the skin
      vertically. Completely developed structure of hair follicle was observed with
      paraffin section and HE staining. 1 week after plucking, new hair had regrown.
      The ratio of cell component was varied, whereas the other component was fixed at
      1 x 10(7) cells. When the number of epidermal cells was reduced to 1 x 10(6)
      cells, the efficiency of hair follicle reconstitution was mostly unchanged. On
      the other hand, the density of newly formed hair was diminished considerably by
      reducing the number of dermal cells to 5 x 10(6) cells or lower. Neither
      epidermal cells nor dermal cells transplanted alone formed hair follicle.
      CONCLUSIONS: Newborn mice skin cells transplanted by chamber method can construct
      a complete model of hair follicle development, which can be used to test the hair
      inductive potential of follicular cells and investigate the molecular mechanism
      regulating hair follicle morphogenesis and cycling.

PMID- 22870711
TI  - [Anatomic study of malar fat pad and aging analysis].
AB  - OBJECTIVE: To discuss the midface aging mechanism through anatomic study of malar
      fat pad. METHODS: 10 fresh adult cadaveric heads (20 sides) fixed by vascular
      perfusion of formalin were used for anatomic study with microsurgery technique
      under microscope. The midfacial ligament and connective tissue between skin and
      subcutaneous fat were observed carefully in different parts of midface. The
      location, shape and extent of malar fat pad was also recorded and photographed.
      RESULTS: The malar fat pad has a triangle shape. The bottom is a curve along the
      orbicularis retaining ligament at the lower eyelid. The fat pad is extended
      internally to the nasolabial fold and labiomandibular fold, externally from the
      major zygomatic muscle end point at the malar surface to the angulus oris and
      submandibular edge. (2) The malar fat pad is composed of meshed fibrous tissue,
      with big fat particles in it. It becomes tight when being stretched in horizontal
      direction along nasolabial fold and loosen when being stretched in vertical
      direction. (3) There is tight connection between skin and fat pad, which is
      divided into four areas as I, II, III, IV. The areas I, II, III are strip-shaped
      parelled to the nasolabial fold. The area IV is a irregular quadrilateral. (4)
      There are six fixation ligaments between malar fat pad and deep tissue:
      orbicularis retaining ligament upper layer of lower eyelid, orbicularis retaining
      ligament substratum of lower eyelid, zygomaticus ligament, zygomatic cutaneous
      ligament, zygomatic cutaneous ligament substratum, platysma There are four
      closely connected areas cutaneous forward ligament, cheek maxilla ligament.
      CONCLUSIONS: between the facial skin and malar fat pad which makes malar fat pad
      and skin keep relatively consistent. The malar fat pad moving down mainly
      resulted from slack of ligaments support which is one of the reasons for aging
      face.

PMID- 22870713
TI  - [The outcome analysis of different age paragraph hearing aid users].
AB  - OBJECTIVE: To compare and analysis outcomes of different age paragraph hearing
      aid users by questionnaires. METHOD: The questionnaire was deployed to 90 hearing
      aid users, 40 females and 50 males, with ages between 19 and 80 years-from junior
      high school education to university education, suffering binaural severe or
      moderate sensorineural deafness. The subjects were devided into 3 groups, the A
      group with ages between 19 and 40 years, the B group with ages between 41 and 60
      years, the C group with ages between 61 and 80 years. After being fitted with
      hearing aids for 6 weeks, 6 months and 12 months, SADL and IOI-HA were applied to
      evaluating 90 subjects. The study was carried out through face to face interview
      or by telephone. RESULT: There were significant differences in SADL scores of
      positive effect, service and Personal image among the 3 groups (P < 0.01). The
      scores of the A group was the highest, and the B group was higher than the C
      group. On the contrary, there were significant differences in SADL scores of
      negative effect among the 3 groups (P < 0.01), with the scores of the A group
      being the lowest, and the B group being lower than the C group. There were also
      significant differences in IOI-HA scores among the 3 groups (P < 0.01). The
      scores of the A group was the highest, and the B group was higher than the C
      group. CONCLUSION: The outcome and satisfaction of hearing aids among different
      age paragraph is improved with the wearing time growth, but the outcome and
      satisfaction of hearing aids are decreased with the age growth.

PMID- 22870712
TI  - [The application of vibrant sound bridge in microtia whose reconstructive
      external auditory canal occurred atresia].
AB  - OBJECTIVE: To investigate the effect of vibrant sound bridge implantation in
      microtia whose reconstructive external auditory canal occurred atresia. METHOD:
      Three cases (2 males and 1 female) of microtia had underwent hearing
      reconstruction operation (Include the external ear canal reconstructive surgery
      and tympanoplasty). The age ranged from 15 to 18 years and the average age was 17
      years. All the 3 cases suffered from conductive hearing loss with the air-bone
      gap ranging from 51.6 to 65.0 dB HL and the average value being 56. 3 dB HL. All
      the 3 cases underwent vibrant sound bridge implantation, including the floating
      mass transducer implanted in the head of stapes in 2 cases and in the niche of
      round window in 1 case. RESULT: The postoperative hearing level improved from
      21.6 to 52.5 dB HL with an average of 32.2 dB HL. There were no complications
      such as vertigo, tinnitus and facial paralysis. CONCLUSION: Through vibrant sound
      bridge implantation, the hearing level of microtia whose reconstructive external
      auditory canal occurred atresia was improved effectively.

PMID- 22870714
TI  - [Risk factors and biological characteristics of infection after cochlear
      implantation].
AB  - OBJECTIVE: To analyze the factors and biological characteristics of infection
      after cochlear implantation so as to control the risk factors and improve the
      treatment of postoperative infection. METHOD: A retrospective study was conducted
      to analyze the clinical data of 316 patients receiving cochlear implantation from
      July 2001 to October 2011. RESULT: Postoperative infection was found in five of
      the 316 cases and one transferred case. The six cases recovered after clinical
      therapy without explantation. One case underwent explantation due to recurrent
      meningitis after implantation of 8 years later. CONCLUSION: The pathogens of
      infection after cochlear implantation are staphylococcus aureus, pseudomonas
      aeruginosa, etc. The key infectious factor is the formation of bacterial biofilm,
      which can be removal by chemical agents to control the postoperative infection,
      especially the flap infection. It is not necessary to remove the artificial
      cochlea when the postoperative infection occurs. Positive perioperative
      interventions and postoperative infection control can improve the outcome of
      cochlear implantation.

PMID- 22870715
TI  - [The effect of dexamethasone in different application on treatment of sudden
      sensorineural hearing loss].
AB  - OBJECTIVE: To investigate the effect of dexamethasone through different methods
      of administration in treatment of sudden sensorineural hearing loss. METHOD: One
      hundred cases of sudden sensorineural hearing loss were retrospectively studied,
      in which patients were divided into 2 groups as A and B. The cases were treated
      with dexamethasone intravenous injection in A group and intratympanic application
      in B group. RESULT: The total effective rate was 66.00% in A group and 68.00% in
      B group. The difference between the total effective rate in group A and B did not
      reach significance in statistics (P > 0.05). CONCLUSION: The effect of
      dexamethasone intravenous injection and intratympanic application on treatment of
      sudden sensorineural hearing loss has no difference.

PMID- 22870716
TI  - [Applied anatomy of facial recess and posterior tympanum related to cochlear
      implantation].
AB  - OBJECTIVE: To investigate the related parameters of temporal bone structure in
      the surgery of cochlear implantation through facial recess approach so as to
      offer a theoretical reference for the avoidance of facial nerve injury and the
      accurate localization. METHOD: In a surgical simulation experiment, twenty human
      temporal bones were studied. The correlation parameters were measured under
      surgical microscope. RESULT: Distance between suprameatal spine and short process
      of incus was (12.44 +/- 0.51) mm. Width from crotch of chorda tympani nerve to
      stylomastoid foramen was (2.67 +/- 0.51) mm. Distance between short process of
      incus and crotch of chorda tympani nerve was (15.22 +/- 0.83) mm. The location of
      maximal width of the facial recess into short process of incus, crotch of chorda
      tympani nerve were (6.28 +/- 0.41) mm, (9.81 +/- 0.71) mm, respectively. The
      maximal width of the facial recess was (2.73 +/- 0.20) mm. The value at level of
      stapes and round window were (2.48 +/- 0.20 mm) and (2.24 +/- 0.18) mm,
      respectively. Distance between pyramidalis eminence and anterior round window was
      (2.22 +/- 0.21) mm. Width from stapes to underneath round window was (2.16 +/-
      0.14) mm. CONCLUSION: These parameters provide a reference value to determine the
      position of cochlear inserting the electrode array into the scale tympani and
      opening facial recess firstly to avoid potential damage to facial nerve in
      surgery.

PMID- 22870717
TI  - [Analysis of psychoacoustic characteristics and audiology tests of tinnitus
      patients with sensorineural hearing loss].
AB  - OBJECTIVE: Tried to find the relationship between tinnitus and each testing
      method, provided information for objective diagnosis and treatment for tinnitus
      patients with sensorineural hearing loss. METHOD: The characteristics of
      audiology tests, including pure tone audiometric, acoustic immittance, middle ear
      muscle reflexes, matching test, distortion products otoacoustic emission(DPOAE)
      were compared in 79 ears of 69 tinnitus patients with sensorineural hearing loss.
      RESULT: The RI positive rate was higher in Convergence curve in tinnitus patients
      of sensorineural hearing loss, with the rate being 51.3%. The detection rates of
      DPOAE were 15.2% in patients of sensorineural hearing loss tinnitus groups, which
      were significant lower than those in control group. CONCLUSION: Psychoacoustic
      techniques can produce a useful amount of clinical data regarding tinnitus in
      different aspects, these data can help clinicians design needed based
      managements. DPOAE test is helpful for the diagnosis of lesions in some tinnitus
      patients.

PMID- 22870718
TI  - [The ear angioplasty and hearing reconstruction of microtia].
AB  - OBJECTIVE: To Study the clinical features of congenital microtia and atresia . To
      evaluate the methods and results of the same microtia surgery, ear canal and
      middle ear reconstruction. METHOD: Statistically analysis of the data of the
      hospitalization microtia 62 ears of 58 cases of patient in our department from
      January 2005 to October 2010 waw conducted. These patients with congenital ear
      malformations are associated with aural atresia, ossicular chain abnormalities,
      severe conduction Deafness. All patients received preoperative temporal bone CT
      examination and reconstruction, hearing examination. Operation was given in two
      phases, first operation aim to form a line of ear, ear canal reconstruction, ear
      reconstruction, the second one aim to line of ear skin graft, cranial angle of
      the ear reconstruction. The preoperative and postoperative data were
      retrospectively analyzed. RESULT: The auricle plus external auditory canal,
      middle ear reconstruction came out with a good shape of the ear and the ear canal
      in close proximity to the normal population. Most patients' hearing were improved
      after surgery. CONCLUSION: Surgeries of patients with congenital ear
      malformations and aural atresia should be carefully designed according to the
      three-dimensional reconstruction of multislice spiral CT reconstruction, which
      can provide information about surgery approach and middle ear abnormality. The
      whole ear shape and hearing ear after reconstruction are improved after the
      surgery.

PMID- 22870719
TI  - [Mutational analysis of candidate genes in a Chinese pedigree with dominantly
      inherited auditory neuropathy].
AB  - OBJECTIVE: Three genes including the OTOF, the DFNB59 and the DIAPH3 have been
      implicated previously in human non-syndromic auditory neuropathy. In this study,
      we aim to investigate whether DIAPH3 gene or the known deafness loci of 25 cloned
      autosomal dominant deafness (DFNA) genes contribute to the nonsyndromic hearing
      loss of a Chinese pedigree with dominantly inherited auditory neuropathy (AN).
      METHOD: Nine members of the kernal pedigree in this family were selected. Genomic
      DNA was isolated from the peripheral leukocytes of the subjects using the
      Puregene DNA Isolation Kits. Firstly, the 5'UTR of DIAPH3 gene was PCR amplified
      in all subjects. Then, the DNA fragments spanning the entire coding regions of
      DIAPH3, GJB2 and GJB3 genes, and 50 exons in other 23 cloned DFNA genes were
      amplified using specific primers. Each fragment was purified and analyzed by
      direct sequencing. The resultant sequence data were compared with the standard
      sequence to identify deafness-associated mutations. RESULT: PCR amplifications
      were successfully conducted. We failed to detect the presence either of c. --172G
      > A mutation in the 5'UTR that have been reported, or any other deafness
      associated mutations in the whole DIAPH3 gene, by sequence analysis. We also did
      not find any known deafness-causing mutations among the 25 cloned DFNA genes.
      CONCLUSION: The DIAPH3 gene, and the known deafness loci of 25 cloned DFNA genes
      seem not contribute to the pathogenesis of this Chinese AN family in this study,
      which suggesting new gene(s) involvement.

PMID- 22870720
TI  - [Clinical and genetic analysis of a patient with Treacher Collins syndrome in
      TCOF1 gene].
AB  - OBJECTIVE: To analyze the clinical and genetic features of a patient with
      Treacher Collins syndrome (TCS), and identify the mutation in TCOF1 gene. METHOD:
      The medical history was taken, and general physical examinations and otological
      examinations were conducted in this patient. Genomic DNA was extracted from this
      patient and his parents and complete TCOF1 gene coding exons were amplified by
      specific PCR primers. Direct sequencing was carried out to identify the
      mutations. The raw data was analyzed with GeneTool software and molecular
      biological website. RESULT: We detected a heterozygous c. 1639 delAG mutation in
      exon 11 of TCOF1, which resulted in a truncated protein lacking normal function.
      This mutation is a novel mutation and the second case identified in exon 11 of in
      TCS. CONCLUSION: TCS patient reported in this study has unique clinical
      phenotype. TCOF1 gene mutation is the specific risk factor.

PMID- 22870721
TI  - [Transdifferention of some supporting cells in the cochlea induced by Ad5
      atoh1/EGFP in the young adult guinea pigs].
AB  - OBJECTIVE: To explore whether the Ad5-atoh1/EGFP could transdifferent the
      supporting cells into the new hair cells in young adult guinea pigs cochlea in
      vivo. METHOD: Twelve healthy pigmented guinea pigs weighted 200-250 g were
      included in this experiment. 5 ul of Ad5-E1/E3 defected-atoh1/EGFP were infused
      into the scala media through a hole made on the lateral wall of the cochlea. Six
      of the 12 animal were killed 2 weeks after the infusion operation. The others
      were killed 4 weeks after the operation. The whole mount of the basal membranes
      were directly observed under the fluorescence microscope for the expression of
      the EGFP (enhance green fluorescent protein) or for the expression of the hair
      cellspecific marker and nuclear after staining with myosin VIIa rabbit polyclonal
      antibody and Dapi dye. RESULT: New cells with big nuclear, ellipse body and
      expressed with EGFP were found in the region near to the outmost row of the outer
      hair cells in 2 animal 2 weeks after the infusion. Moreover there were 3 animals
      with specific morphologic new cells in the location where ever been located by
      the outer hair cells and the region as 2 weeks animals 4 weeks after the
      infusion. Those cells were stained by myosin VIIa antibody. CONCLUSION: Atoh1
      gene could transdifferent some supporting cells in the basal membrane into hair
      cell like cells in young adult guinea pigs in vivo. These supporting cells locate
      in the region of outer hair cells and the basal membrane which do not belong to
      the region of outer hair cells.

PMID- 22870722
TI  - [The effect of adenoidectomy in different operative methods on the function of
      eustachian tube].
AB  - OBJECTIVE: To compare the effect of two different approaches in curettage of
      adenoid hypertrophy on eustachian tube function: the endoscopic assisted
      transoral adenoidectomy, and the traditional transoral curette adenoidectomy.
      METHOD: Clinical data of adenoid hypertrophy patients who underwent surgery
      therapy were prospectively analyzed; Eustachian tube function were compared among
      them. RESULT: Both traditional curettage of adenoids through mouth(group TCA) and
      endoscopic assisted transoral adenoidectomy (group ETA) significantly improved
      eustachian tube function (P < 0.01), while group ETA seemed to have a better
      outcomes (P < 0.01). CONCLUSION: Both traditional curettage of adenoids through
      mouth and the endoscopic assisted transoral adenoidectomy can significantly
      improve eustachian tube function, and the endoscopic assisted transoral
      adenoidectomy produces a better outcome.

PMID- 22870723
TI  - [Research of modified skin flap of external canal in auditory canal shaping to
      enlarge].
AB  - OBJECTIVE: To investigate the new method of modified skin flap of external canal
      in auditory canal shaping to enlarge at radical mastoidectomy in endaural
      incision. METHOD: From 1999 to 2009, 412 patients with 428 ears in operation were
      randomly divided into two groups. Patients underwent open mastoidectomy and some
      patients were performed concurrent tympanoplasty. A group (control group)were
      operated in traditional skin flap of external canal, B group is modified group.
      Bleed and effusion from the wound surface, the time of dry ear and the change of
      diameter of extermal acoustic meatus after one year were observed after the
      surgeries and deal the results with SPSS. RESULT: The difference had statistical
      significance in bleed and effusion from the wound surface, the time of dry ear
      and the shrink of external acoustic meatus in 12 months among two groups.
      CONCLUSION: Modified skin flap of external canal in auditory canal shaping to
      enlarge can help to make a no-wound dehiscence by wiping out the raw surface of
      external acoustic meatus. It is better than traditional skin flap of external
      canal.

PMID- 22870724
TI  - [The clinical application of recombinant human epidermal growth factor in the
      treatment of traumatic tympanic membrane perforation].

PMID- 22870725
TI  - [Clinical analysis of 3 073 cases neonatal hearing screening].

PMID- 22870726
TI  - [Postauricular primary dermatofibrosarcoma protuberans: a case report].
AB  - Dermatofibrosarcoma protuberan is a maligant tumor with low malignancy. The major
      clinical manifestation is a hard nodule increasing slowly from skin surface, pale
      purple. Pathological feature as a wheel shape or a multilayer aligned fibroblast.

PMID- 22870727
TI  - [Clinical characteristics of solitary plasmacytoma of temporal bone].
AB  - Patient of plasmacytoma of temporal bone often suffered from evident symptom in
      unilateral ear and obvious damage of bone. Clinical characteristics, imaging
      examination and histopathology can established an accurate diagnose. The therapy
      will be surgery and followed radiotherapy.

PMID- 22870728
TI  - [Research progress of acute kanamycin sulfate-induced deafness in guinea pig].
AB  - To present a summary of current knowledge regarding acute kanamycin sulfate
      induced deafness in guinea pig, by reviewing the published literature. Animal
      model of acute deafness induced by a single dose of kanamycin sulfate in
      combination with ethacrynic acid or furosemide in guinea pig was usually used to
      investigate the mechanism of cochlear cell degeneration. There were different
      time sequences of cell degeneration of spiral ganglion cell and hair cell in
      different studies. The findings may result from different doses, order of two
      drugs administration or time point chosen. There remains scope for further
      research in chronic kanamycin-induced deafness, which more replicates the type of
      exposure to people than acute deafness.

PMID- 22870729
TI  - [Worry about talent in first line health care].

PMID- 22870730
TI  - Air pollution and health--air quality standards.

PMID- 22870731
TI  - The influence of air pollution on health: mechanistic implications.

PMID- 22870732
TI  - Air pollution in Belgium: will we be able to comply with the European standards?

PMID- 22870733
TI  - Prevalence of atrial fibrillation in adults participating in a large-scale
      voluntary screening programme in Belgium.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a common arrhythmia in clinical practice.
      AF fulfils many of the criteria for a screening programme. No data about the
      prevalence of AF in non-hospitalized patients are available in Belgium. The aim
      of the study was to assess feasibility and effectiveness of a nationwide
      organized voluntary screening programme in the general population in Belgium.
      METHODS: A total of 13.564 participants were screened, of whom 10,758 were older
      than 40 years (GSP group). Participants filled in stroke risk stratification
      questionnaires (CHADS2 and CHA2DS2-VASc). A one-lead electrocardiogram was
      performed. RESULTS: 228 participants had AF at the time of screening (AF group),
      with 125 women and 103 men (i.e., 1.9% and 2.6% of total women and men),
      representing a prevalence of 2.2% (95% CI 1.3% and 3.0%) of the screened
      population. Age of the AF group was 67 +/- 12 y (range 40-87 y). Using the CHADS2
      score, 58% of participants with a positive AF screening had a high risk score,
      and 21% had an intermediate risk score. Using the CHA2DS2-VASc-score, 72% of the
      participants had a high risk score, and 21% had an intermediate risk score.
      CONCLUSION: AF was present in 2.2% of the respondents. At least 60% of AF group
      had an increased risk for thrombo-embolism. Although substantial methodological
      issues limit the exact interpretation of these results, the present study shows
      that a volunatry screening programme with a simple screening protocol is able to
      detect an important number of patients with previously undetected AF.

PMID- 22870735
TI  - Weber classification in cardiac rehabilitation.
AB  - OBJECTIVE: Upon beginning cardiac rehabilitation after a cardiac event,
      stationary cycle exercise ergometry is commonly performed to determine maximum
      exercise aerobic capacity (peak oxygen uptake [peak VO2]) and anaerobic
      threshold. The Weber classification stratifies patients based on peak VO2 and
      anaerobic threshold to define functional physical capacity. The purpose of the
      present study was to evaluate the Weber classification in patients entering
      cardiac rehabilitation. METHODS AND RESULTS: In 275 consecutive patients entering
      cardiac rehabilitation from January 2009 to March 2010, peak VO2,and anaerobic
      threshold were measured before and after cardiac rehabilitation. Consecutive
      patients with different cardiac conditions were compared, including percutaneous
      intervention (PCI) without myocardial infarction, myocardial infarction, coronary
      artery bypass graft (CABG), and heart failure. The Weber class of most patients
      entering cardiac rehabilitation was low, usually Weber class C for women and
      class B for men (peak VO2 was 13 +/- 4 ml/kg/min in women and 15 +/- 3 ml/kg/min
      in men). Before the cardiac rehabilitation the greatest values of peak VO2 were
      associated with PCI and the lowest values with heart failure, with significantly
      greater average values for patients with PCI than heart failure before cardiac
      rehabilitation (PCI, 16 +/- 2 ml/kg/min versus heart failure, 11 +/- 3 ml/kg/min,
      P < 0.05). There was no statistical difference between the CABG and heart failure
      groups in mean peak VO2 before cardiac rehabilitation (CABG, 13 +/- 2 ml/kg/min
      versus heart failure, 11 +/- 3 ml/kg/min, NS) and between the PCI and myocardial
      infarction groups (PCI, 16 +/- 2 ml/kg/min versus myocardial infarction, 15 +/- 4
      ml/kg/min, NS). At the end of cardiac rehabilitation, the Weber class was
      improved of one class for patients with PCI, myocardial infarction, CABG, and
      women with heart failure but not for men with heart failure. CONCLUSIONS: The
      Weber classification was useful to monitor improvement in functional capacity
      from the beginning to the end of cardiac rehabilitation. Cardiac rehabilitation
      improved physical function. But the Weber classification in itself because of the
      low classes found among many patients after a cardiac event and before a cardiac
      rehabilitation could underestimate the results of this one.

PMID- 22870734
TI  - Familial predisposition to vasovagal syncope.
AB  - OBJECTIVE: A handful of studies suggest a familial predisposition to vasovagal
      syncope (WS) but the scope of information available to date is poor. The aim of
      our study was to evaluate the prevalence of vasovagal syncope and its familial
      occurrence in the young. METHODS AND RESULTS: The studied group consisted of 281
      women and 111 men, aged 18-32 years. Forty-seven percent of the population had
      one brother or sister, and the mean number of individuals per family was 4.4 +/-
      1.0. The questionnaire consisted of 30 questions regarding syncopal history.
      Syncope was reported in 32.1% of the patients studied (36.7% in women vs. 20.7%
      in men; P < 0.05), 29.1% of mothers, 16.8% of fathers, 30.9% of sisters and 14.2%
      of brothers. Logistic regression analysis revealed that positive history
      regarding the syncope in the whole group of students was related to the female
      gender (OR 2.17; CI: 1.28-3.7), the history of a syncope in mother (OR 1.74; CI:
      1.09-2.78) and the history of a syncope in father (OR 2.22; CI: 1.28-3.86; P <
      0.001). CONCLUSIONS: A positive history of syncope in male relatives increases
      the risk of syncope in men and women, whereas a positive history of syncope in
      female relatives increases the risk of syncope in women only. Female gender
      independently of the family history increases the risk of syncope. The genetics
      of the vasovagal syncope could be polygenic but the mechanisms of a transmission
      remain unclear to date.

PMID- 22870736
TI  - The role of brain natriuretic peptide and serum triiodothyronine in the diagnosis
      and prognosis of chronic heart failure.
AB  - OBJECTIVE: The objective of this paper was to investigate the diagnostic and
      prognostic value of plasma B type natriuretic peptide (BNP) and serum
      triiodothyronine (T3) in chronic congestive heart failure (CHF). METHODS: 156
      cases of CHF patients and 75 cases of cardiac function I patients hospitalized
      over the same period were utilized in this study. On admission, the patient's BNP
      and T3 plasma concentrations were measured. The correlation analysis of plasma
      BNP and T3 in CHF patients with cardiac function classification was conducted.
      RESULTS: According to the NYHA grading systems, the plasma BNP levels in patients
      with II, III, and IV grade CHF were significantly higher than those with cardiac
      function I (P < 0.05); BNP levels and NYHA grading of cardiac function correlated
      positively. The BNP concentrations increased with CHF progression (P < 0.01). The
      T3 level and NYHA grading of cardiac function correlated negatively.TheT3 level
      decreased as the degree of heart failure increased. Using CHF in combination with
      BNP to predict the occurrence of CHF had a sensitivity value of 90.8% with 95.5%
      specificity, 86.3% accuracy, and a negative predictive value of 87.7%.
      CONCLUSIONS: Plasma BNP was more sensitive than T3 in the diagnosis of CHF. The
      T3 was more meaningful than the BNP in the prognosis of CHF. The BNP and T3
      combination detection was more valuable in determining the severity of CHF and
      prognosis.

PMID- 22870737
TI  - The exercise treadmill test: predictors of true presence of significant coronary
      stenosis in patients with severe ST-segment depression.
AB  - OBJECTIVE: Significant coronary stenosis is not always present in patients with
      even severe (2.0 mm) ST-segment depression in the exercise treadmill test
      (ETT).The purpose of this study was to determine the clinical and ETT-related
      predictors of true presence of significant coronary stenosis in this population.
      METHODS: A total of 212 consecutive patients who showed severe ST-segment
      depression in ETT and underwent coronary angiography were included in this study.
      Clinical characteristics and ETT parameters were compared according to presence
      or absence of significant coronary stenosis. Logistic regression analysis was
      performed to identify the independent predictors of significant coronary
      stenosis. RESULTS: Significant coronary stenosis was present in 105 (49.5%)
      patients. Multivariable regression analysis showed that ST-segment depression
      persisting into recovery (odds ratio: 11.1, 95% confidence interval: 2.4-51.7, P
      = 0.002), ST-segment depression occurring at stage II (odds ratio: 10.3, 95%
      confidence interval: 2.0-54.1, P = 0.006), ST-segment depression combined at I,
      aVL, or V(2-3) (odds ratio: 10.5, 95% confidence interval: 1.3-81.8, P = 0.025),
      hypertension (odds ratio: 4.2, 95% confidence interval: 1.3-13.5, P = 0.007), and
      typical chest pain (odds ratio: 4.1, 95% confidence interval: 1.2-14.6, P =
      0.023) were the predictors of the presence of significant coronary stenosis.
      CONCLUSIONS: The present study showed that the independent predictors of true
      presence of significant coronary stenosis in patients with severe (> or = 2.0 mm)
      ST-segment depression in ETT are ST-segment depression which begins at stage II
      or persists into recovery or occurs in I, aVL, or V(2-3), hypertension, and
      typical chest pain.

PMID- 22870738
TI  - Infections of implantable cardiac rhythm devices: predisposing factors and
      outcome.
AB  - BACKGROUND AND OBJECTIVE: Infection is a serious complication of cardiac devices.
      We aimed to describe predisposing factors and outcome of permanent pacemaker
      (PPM) and implantable cardioverter/defibrillator (ICD) infections. METHOD: We
      reviewed cardiac device infections diagnosed at the Yuksek Ihtisas Hospital
      Ankara, Turkey, between 2004 and 2010 retrospectively. Demographic and clinical
      data were collected, descriptive analysis was performed. RESULTS: From 2004 to
      2010, a total of 1916 devices were implanted. Thirty-four cases of confirmed
      device infections were identified giving an infection rate of 1.7%. Seventy-three
      percent of the cases were men. Mean age was 58 +/- 19 years. Twenty-two patients
      had a PPM, 12 had an ICD or cardiac resynchronization therapy (CRT). Diabetes
      mellitus, hypertension, cardiac failure, anaemia and immune suppression were
      prominent comorbidities. Previously, 6 (17%) patients had a history of
      replacement, 6 (17%) had revision, 3 (8%) had haematoma. Ten (29%) patients
      reported a history of long hospital stay and 13 (38%) patients had multiple
      hospitalizations. Pocket infection (70%) was the most common clinical
      presentation. Ninety-one percent of patients were cured with both device removal
      and antibiotic administration. Complications of cardiac device infections
      included septic emboli, acute renal failure, inotropic infusion requirement which
      were mostly seen among patients with endocarditis. Five patients suffered
      relapsing infection.Three patients died, among them two had infective
      endocarditis. CONCLUSION: Cardiac device infections have been encountered more
      often in recent years. Cure of device infections is achievable in a majority of
      patients treated with antimicrobial treatment and complete device removal
      although device-related endocarditis can have an aggressive course.

PMID- 22870739
TI  - Cardiac resynchronization therapy in clinical responders: right ventricular
      echocardiographic changes at mid-term follow-up.
AB  - OBJECTIVE: The objective of this study was to assess the mid-term effects of
      cardiac resynchronization therapy on systolic function and remodelling of the
      right ventricle in clinical responders and non-responders. METHODS: A
      biventricular system was implanted between July 2005 and May 2008 in 58 patients
      with heart failure NYHA class II-IV. At baseline, three and 15 months after
      implantation, the following parameters were determined: NYHA class, quality of
      life, six-minute walk test, echocardiography including assessment of right
      ventricular systolic function by tricuspid annular plane systolic excursion and
      by pulsed tissue Doppler imaging (myocardial peak systolic velocity was measured
      at the tricuspid annulus). We also assessed the presence of ventricular
      dyssynchrony. RESULTS: There were no significant changes after three months of
      cardiac resynchronization therapy on right ventricular systolic function and
      remodelling in responders and non-responders. Among responders, we found a
      statistically significant improvement of right ventricular systolic function and
      also a significant decrease in the size of the right ventricle after 15 months of
      therapy (systolic excursion before therapy 17.8 +/- 4.0 mm vs. 19.4 +/- 3.7 mm, P
      < 0.05, after therapy; peak systolic velocity initially 11.9 +/- 2.9 cm/s vs 12.7
      +/- 3.2 cm/s; right ventricle size before therapy 29.3 +/- 5.0 mm vs. 27.8 +/-
      4.2 mm, P < 0.05, after therapy. These changes were not observed in non
      responders. CONCLUSIONS: Fifteen months after cardiac resynchronization therapy,
      we found a statistically significant improvement of right ventricular systolic
      function and a significant reduction of right ventricular size in responders to
      cardiac resynchronization therapy.

PMID- 22870740
TI  - The predictive value of QRS duration in response to levosimendan therapy in
      patients with decompensated heart failure.
AB  - PURPOSE: We aimed to investigate the role of QRS duration on the surface
      electrocardiogram (ECG) in predicting response to levosimendan therapy in
      patients with acute systolic heart failure. METHODS: Patients with an ejection
      fraction (EF) lower than 35% who required intravenous inotropic support despite
      optimal heart failure therapy were included in this study. Patients were divided
      into two groups according to QRS durations on ECG. Group 1 (n=16) included
      patients with a QRS duration equal to or shorter than 120 ms and group 2 (n=14)
      included patients with a QRS duration longer than 120 ms. New York Heart
      Association (NYHA) functional class, plasma BNP levels and echocardiographic
      measurements were compared within and between groups before and after the
      infusion. RESULTS: In both groups statistically significant improvement was
      observed in NYHA class, plasma BNP levels and left ventricular end-systolic
      diameter after the levosimendan infusion compared to baseline (P < 0.025). In
      addition, in group 1 patients, left atrial diameter, left atrial volume, left
      ventricular end-diastolic diameter, left ventricular end-diastolic volume, left
      ventricular end-systolic volume (LVESV), left ventricular EF, mitral E velocity,
      mitral annular Aa and Sa parameters improved after the infusion compared to the
      baseline values (P < 0.025). Comparison of both groups revealed improvement of
      NYHA class, an increase of left ventricular EF and a signficant decrease of LVESV
      after levosimendan in group 1 (P < 0.05). CONCLUSION: QRS duration on ECG may be
      used as a practical bedside indicator in estimating short-term response to
      levosimendan therapy.

PMID- 22870741
TI  - Influence of acute stress on cardiac electrophysiological stability in male
      goats.
AB  - OBJECTIVE: Stress plays an important role in the pathogenesis of ventricular
      arrhythmias. This study was designed to examine the effect of acute stress and
      metoprolol, a beta adrenergic receptor blocker, on cardiac electrophysiological
      stability of male goats. METHODS: Fifteen male goats were randomly divided into
      three groups: (i) control animals (n=5), (ii) a compound stimuli group including
      noise and red flash (n=5), (iii) and a compound stimuli group with metoprolol
      treatment (n=5). Plasma catecholamines were determined by using high performance
      chromatography with electrochemical detection. Heart rate turbulence (HRT) and
      heart rate variability (HRV) were analysed with the MGY-H12L analysis system.
      Also, the ventricular fibrillation threshold (VFT) and the ventricular vulnerable
      period (VVP) were determined by programmed S1S2 stimulus with bipolar electrodes
      at the apex of the goat hearts. RESULTS: Compound stimuli increased plasma
      catecholamine levels progressively and decreased the negative value of turbulence
      onset (TO), turbulence slope (TS), SDNN, PNN50. Moreover, compound stimuli
      broadened VVP and decreased VFT significantly. Although metoprolol treatment
      failed to affect plasma catecholamine levels, TS and PNN50 value of the compound
      stimuli group, it significantly increased the negative value of TO, SDNN, VFT and
      narrowed VVP. CONCLUSION: Our data demonstrates that compound stimuli can induce
      acute stressful reactions, and decrease the cardiac electrophysiological
      stability of male goats, which can be counteracted by metoprolol treatment.

PMID- 22870742
TI  - Early detection of cardiac dysfunction by BNP in beta-thalassaemia major
      patients.
AB  - BACKGROUND: Cardiomyopathy is the leading cause of mortality in beta-thalassaemia
      major (BTM) patients. Brain natriuretic peptide (BNP) has been used for latent
      cardiac dysfunction in heart patients other than thalassaemic patients. The
      objective was to determine its role in subclinical detection of iron-induced
      cardiotoxicity in BTM patients. METHODS AND RESULTS: EDTA plasma was taken from
      33 thalassaemic patients and 29 healthy controls, stored at -20 degrees C until
      analysis. The median (range) age of thalassaemic major children was 10 (6-21)
      years and mean serum ferritin levels were 3956 (1929-6979) microg/L. The BTM
      children had significantly (P < 0.01) higher BNP median (range) 83.94 (45.93
      196.80) pg/mL as compared to controls 55.62 (32.58-99.84) pg/mL. Mitral E-wave
      velocities were found higher in patients rather than controls (132.12 +/- 29.40
      vs. 117.70 +/- 24.81; P < 0.05). The E/Ea ratio was significantly higher in BTM
      patients than in the control group (16.35 +/- 6.01 vs. 19.26 +/- 4.67; P =
      0.001). We found a significant positive correlation between BNP and E/Ea ratio (r
      = 0.53; P < 0.01). BNP at a cut-off value of 84.39 pg/mL was highly accurate in
      ruling out diastolic dysfunction (E/Ea < 8) with a sensitivity of 80% and a
      specificity of 88%. CONCLUSION: BNP has a good predictive value in detecting
      latent LV dysfunction in BTM patients.

PMID- 22870743
TI  - Atypical presentation of tuberculous constrictive pericarditis: case report and
      review of the literature.
AB  - An 18-year-old Romanian man with no known history of cardiac disease was admitted
      to the hospital for the management of right heart failure and bilateral pleural
      effusions. Further investigations revealed mediastinal lymph nodes and a
      constrictive cardiac haemodynamic pattern. Lymph node biopsy demonstrated a
      purulent liquid from which cultures were positive for Mycobacterium tuberculosis.
      The patient improved rapidly with conservative medical management involving
      antituberculous therapy and diuretics. Tuberculous constrictive pericarditis is
      rare in Western countries but may still present in migrant populations. As shown
      in this case, the possibility of atypical and reversible presentations with
      neither calcifications nor thickening of the pericardium must not be forgotten.

PMID- 22870744
TI  - A dilemma in the electrophysiology lab: where is the coronary sinus in a patient
      with left inferior vena cava with hemiazygos continuation?
AB  - Occasionally, electrophysiological interventions are complicated by an unusual or
      an anomalous cardiovascular anatomy. We report our experience of a case of situs
      ambiguous and symptomatic heart failure of which anomalous venous anatomy and
      coronary sinus variation had prevented a successful endocardial placement of a
      left ventricular lead for cardiac synchronization therapy.

PMID- 22870746
TI  - Ciprofloxacin and the risk for cardiac arrhythmias: culprit delicti or watching
      bystander?
AB  - Torsades de pointes (Tdp) is a polymorphic form of ventricular tachycardia and a
      life-threatening event. A variety of non-cardiovascular drugs, including
      fluoroquinolone antibiotics, have been shown to possess arrhythmogenic
      properties. However, only 25 cases of ventricular tachycardia associated with the
      use of ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin
      have been reported in the United States between 1996 and 2000, with ciprofloxacin
      being involved in two cases. Thus, it has been argued that the arrhythmogenic
      property of ciprofloxacin may derive from its interaction with other potentially
      arrhythmogenic drugs. We report: (i) a case of torsades de pointes (Tdp)
      associated with oral ciprofloxacin in a patient with concomitant risk factors and
      (ii) a review of the literature on pharmacokinetic interactions involving
      ciprofloxacin resulting in cardiac arrhythmias.

PMID- 22870745
TI  - Uncorrected acyanotic tetralogy of fallot decompensated in adulthood after an
      acute onset of malaria.
AB  - Tetralogy of Fallot is the most frequent cyanotic congenital heart disease.
      Usually, the condition is diagnosed and treated during the first year of life.
      Few reports of uncorrected tetralogy of Fallot reaching adulthood are found in
      the literature. Occasionally the pulmonary obstruction is relatively mild and the
      presentation is with minimal cyanosis. This particular situation is called "pink
      tetralogy" or "acyanotic tetralogy". For these adults surgical repair is still
      recommended, since the results of surgery are good and the operative risk is low.
      We report the case of a 55-year-old man with an uncorrected acyanotic tetralogy
      of Fallot diagnosed after right cardiac failure triggered by an acute onset of
      malaria.

PMID- 22870747
TI  - Subacute papillary muscle rupture following percutaneous mitral valvuloplasty.
AB  - INTRODUCTION: Mitral valve stenosis is becoming increasingly rare in
      industrialized countries thanks to the almost complete extinction of rheumatic
      valve disease. Nevertheless, every cardiologist will encounter a few cases,
      notably in elderly with degenerated calcified mitral valves or in younger
      immigrants coming from parts of the world with endemic rheumatic valve disease.
      Patients usually present with progressive dyspnoea due to increased left atrial
      and pulmonary artery pressures and a decline in cardiac output secondary to
      preload reduction. Introduced by Inoue in 1984, percutaneous balloon mitral
      valvuloplasty constitutes an elegant treatment modality in patients with
      appropriate valvular anatomy, with excellent immediate results and long-term
      outcome.The original Inoue technique, based on the surgically closed
      commissurotomy, employs the eponymous balloon to crack the mitral commissures to
      separate the mitral leaflets along their natural plane thereby enlarging the
      mitral valve area. Similar but slightly different techniques have emerged
      throughout the years and have extensively been used in the clinic. One of them is
      the so-called double balloon valvuloplasty, first described in Saoudi Arabia by
      Al-Zaibag, during which two balloons are positioned side-by-side across the
      stenotic valve and inflated simultaneously. Mitral regurgitation is relatively
      common after balloon dilatation, but is mostly mild and caused by excessive
      commissural tearing or slight prolapse of the anterior leaflet. We present a rare
      case of severe mitral regurgitation following double balloon mitral valvuloplasty
      due to papillary muscle rupture.

PMID- 22870748
TI  - Vertebral artery dissection secondary to defibrillation threshold testing.
AB  - We report a case of vertebral artery dissection presenting 2 days after ICD
      implantation with defibrillation threshold testing in a 57-year-old man with
      ischemic cardiomyopathy. The association between vertebral artery dissection and
      neck trauma and the role of DFT testing in ICD implantation are discussed.

PMID- 22870749
TI  - The link between intracranial haemorrhage and cardiogenic shock: a case of
      Takotsubo cardiomyopathy.
AB  - Myocardial dysfunction occurs frequently during subarachnoid haemorrhage (SAH)
      and it is often referred to as neurogenic stunned myocardium (NSM). Takotsubo
      cardiomyopathy (TTC), which can lead to life-threatening acute heart failure, has
      been considered a possible complication of SAH. Actually, NSM and TTC are
      believed to share the same pathophysiological mechanisms and are likely a
      manifestation of the same disease. We report a case of a 64-year-old woman with
      SAH and cardiogenic shock due to acute left ventricular dysfunction.
      Echocardiography and ventriculography showed the typical pattern of TTC.
      Angiography excluded coronary artery disease or coronary spasm. Short-term
      inotropic support was necessary. Rapid recovery of left ventricular function was
      observed after 8 days. Acute myocardial dysfunction due to TTC in the setting of
      SAH may lead to cardiogenic shock which is difficult to treat. Patients with SAH
      and haemodynamic instability warrant a careful assessment of ventricular function
      on admission to rule out TTC

PMID- 22870750
TI  - Chronic radial artery occlusion after transradial catheterization. Re
      canalization via an ipsilateral ulnar artery.
AB  - Transradial approach to coronary angiography is a progressive and increasingly
      more often used technique. Apart from its advantages, radial artery occlusion
      (RAO) represents the most serious drawback. Re-canalization of an iatrogenic RAO,
      although asymptomatic in the majority of cases, remains a discussed and
      challenging topic. Besides its clear indications in symptomatic patients, it
      still remains questionable whether to perform this procedure in order to enable
      future repeated cannulations using the same access site and preserving the other
      remaining sites. For this particular reason we performed an antegrade re
      canalization of an unrecognized RAO, likely a result of a previous transradial
      approach intervention. After a failed radial approach, the intervention was
      successfully performed via an ipsilateral ulnar artery. Following an
      uncomplicated coronary re-catheterization, RAO was angiographically diagnosed and
      re-canalized via the same (ulnar) access site using standard coronary equipment.
      Radial and ulnar artery patency were examined and checked on the following day
      and one month later using duplex ultrasonography.

PMID- 22870751
TI  - Myocardial infarction and tuberculosis.
AB  - ST-elevation acute myocardial infarction (AMI) is a critical illness with a high
      mortality rate. Cases of AMI accompanied by active tuberculosis are rarely
      reported. Percutaneous coronary intervention (PCI) is an important procedure in
      the treatment of ST-elevation AMI; it can significantly improve the prognosis and
      quality of life and reduce mortality. Anticoagulants and antiplatelet medications
      are administered before, during, and after PCI. However, for patients with ST
      elevation AMI accompanied by active tuberculosis, anticoagulation and
      antiplatelet therapy may lead to pulmonary haemorrhage, haemoptysis, and serious
      treatment difficulties. Some authors even regard pulmonary tuberculosis as a
      contraindication of PCI. In this study, we have reported 3 patients with ST
      elevation AMI accompanied by active tuberculosis who underwent PCI at our
      hospital between July 2007 to September 2010, and obtained satisfactory outcomes.

PMID- 22870752
TI  - Aberrant LAD arising from the right sinus of Valsava.

PMID- 22870753
TI  - Rapidly progressing coronary artery aneurysm and left ventricular diverticulum.

PMID- 22870755
TI  - [Promoting organ donation, a necessity].

PMID- 22870754
TI  - Relations between professional medical associations and the health-care industry,
      concerning scientific communication and continuing medical education: a policy
      statement from the European Society of Cardiology.
AB  - Physicians have an ethical duty to keep up-to-date with current knowledge.
      Professional medical associations such as the European Society of Cardiology
      (ESC) support these obligations. In Europe, the costs of continuing medical
      education (CME) are insufficiently supported from governments and employers;
      however, medical associations have been criticized for accepting alternative
      financial support from industry. Medical education and training in research
      include learning how to assess the quality and reliability of any information.
      There is some risk of bias in any form of scientific communication including
      intellectual, professional, and financial and it is essential that in particular,
      the latter must be acknowledged by full disclosure. It is essential that there is
      strong collaboration between basic and clinical researchers from academic
      institutions on the one hand, with engineers and scientists from the research
      divisions of device and pharmaceutical companies on the other. This is vital so
      that new diagnostic methods and treatments are developed. Promotion of advances
      by industry may accelerate their implementation into clinical practice.
      Universities now frequently exhort their academic staff to protect their
      intellectual property or commercialize their research. Thus, it is not commercial
      activity or links per se that have become the target for criticism but the
      perceived influence of commercial enterprises on clinical decision-making or on
      messages conveyed by professional medical organizations. This document offers the
      perspective of the ESC on the current debate, and it recommends how to minimize
      bias in scientific communications and CME and how to ensure proper ethical
      standards and transparency in relations between the medical profession and
      industry.

PMID- 22870756
TI  - [Receiving a cancer diagnosis].

PMID- 22870757
TI  - [Physical activity for cardiovascular disease prevention].

PMID- 22870758
TI  - [Life expectancy and good health in Europe].

PMID- 22870759
TI  - [Inappropriate medication use in the elderly].

PMID- 22870760
TI  - [Relational care, a model to question].
AB  - The nurse-patient relationship constitutes a major part of nursing practice.
      Conceptualised in numerous works aimed at professionals as well as students and
      incorporated by nurses as a fundamental basis of their professional practice, it
      seems to suffer from a failure to consider it on the basis of real nursing
      practice conditions. There are, however, several avenues to explore to encourage
      discussion on this point.

PMID- 22870761
TI  - [Perfusion and flow control, recommendations and issues].
AB  - A reflection on perfusion and the use of flow control systems was carried out in
      the Hospices Civils, Lyon (69) in 2008. This initiative was conducted over 3
      years by the Pharmacists, the Central Care Directorate and the Committees for
      drugs and sterile medical devices. In particular, recommendations for the use of
      flow regulators were issued and their impact was evaluated at 8 months of their
      distribution by a survey on nursing practices.

PMID- 22870762
TI  - [Breast cancer and the hand-foot syndrome].
AB  - Regarding patients being treated for breast cancer and on oral capecitabine, the
      main side effect is the hand-foot syndrome (HFS), or Palmar-Plantar
      Erythrodysesthesia (PPE).). This could be inconvenient or even debilitating
      depending on the grade. The Day Care Centre at the Institut Curie in Paris (75)
      conducted a prospective study on patients treated with oral capecitabine for
      advanced breast cancer, to assess the rate of appearance of the hand-foot
      syndrome and the impact of paramedical follow-up on the occurrence of this side
      effect.

PMID- 22870763
TI  - [Septic shock. An interdisciplinary emergency].

PMID- 22870764
TI  - [The definition and epidemiology of septic shock].
AB  - Septic shock is the ultimate consequence of the systemic inflammatory response
      generated by the infection. Its steadily increasing incidence and its morbidity
      and mortality are a major public health issue.

PMID- 22870765
TI  - [The pathophysiology of septic shock].
AB  - Understanding of the pathophysiology of septic shock has benefitted from recent
      advances. These advances enable the validation of current treatment but also the
      development of new therapeutic approaches.

PMID- 22870766
TI  - [Septic shock treatment concerns].
AB  - The establishment of care procedures in the treatment of septic shock may
      decrease the risk of mortality. Prognosis of this condition may improve through
      teamwork in the Intensive Care Unit.

PMID- 22870767
TI  - [Nursing management of ventilation and sedation in patients suffering from septic
      shock].
AB  - A significant number of intubated, ventilated and sedated patients suffering from
      septic shock develop acute respiratory distress syndrome (ARDS). The supervision
      by a multidisciplinary team optimises both the management of ventilation and the
      sedation analgesia of the patient. The nursing supervision and care related to
      this pathology are specific.

PMID- 22870768
TI  - [The role of the nurse in the use of catecholamines in septic shock].
AB  - The catecholamine contribution in septic shock is an important therapeutic area.
      It requires good pharmacological understanding of these molecules on the part of
      nursing staff, their positive effects but also their adverse effects which may
      lead to worsening of hemodynamic instability in patients.

PMID- 22870769
TI  - [The research nurse and septic shock].
AB  - Clinical medical research in septic shock is complex and represents a substantial
      additional workload for nurses. The clinical research nurse develops reference
      tools to simplify to a maximum this work.

PMID- 22870770
TI  - [The nurse/nurses' aide combination and septic shock].
AB  - The management of patients suffering from septic shock, due to its complexity and
      the numerous risk factors inherent in this pathology, is optimised by nurses and
      nurse auxiliaries working in pairs.This also helps families to come to terms with
      the intimidating environment of resuscitation.

PMID- 22870771
TI  - [The role of the psychologist in the intensive care unit with patients and their
      relatives].
AB  - The ICU stay is a potential source of psychological trauma for patients but also
      for their relatives. The presence of a psychologist can help overcome these
      difficulties. The nursingteam should be alerted to the identification of symptoms
      of distress.

PMID- 22870772
TI  - [Quality of life after a stay in the intensive care unit].
AB  - The study of quality of life is a critical indicator in evaluating the care of
      patients in intensive care. This must be measured to detect signs of
      psychological and physical sequelae and adapt patient support accordingly.

PMID- 22870773
TI  - [Advances in research of septic shock].

PMID- 22870774
TI  - [Septic shock. Bibliography].

PMID- 22870775
TI  - [Ethnography and nursing research].
AB  - Ethnography, a qualitative research methodology, is used to describe culture
      shared by a group or to explore a cultural phenomenon. Nurse researchers seeking
      better understanding of the health practices of certain cultural groups became
      rapidly interested in it. Its application relies on a process that requires time.

PMID- 22870776
TI  - [Patient education at diagnosis].

PMID- 22870777
TI  - [Simulation of bioequivalence study on the base of dissolution curves].
AB  - A computer method based on the in vitro dissolution of drug preparations has been
      elaborated for the estimation of bioequivalence. The method generates a
      "dissolutaion surface" from the parameters of time (X-axis), from pH (Y-axis) and
      from the dissolved amount (A) in % of the drug. This dissolution surface allows
      the determination of the general dissolution curve of the test and reference
      preparations. By supposing that the absorption rate constant is known from the
      literature, the change of the amount of dissolved drug as the function of time
      can be determined. On the base of this function the maximum amount of the
      dissolved drug in the gastrointestinal tract and the AUC can be calculated. and
      the test/reference ratio can be determined. In the case of linear
      pharmacokinetics these ratios are identical to the ratios of parameters that can
      be calculated in the circulation. By generating parameters between the allowed
      biological limits the dissolved drug-time curves of "volunteers" in the necessary
      number are created with the randomly generated "residence times" and their
      confidence intervals can be determined, i.e., on the base of dissolution curves
      bioequivalence can be estimated.

PMID- 22870778
TI  - [Comparative study of crystallization processes in case of glycine
      crystallization].
AB  - In our work, the effect of crystallization methods and their parameters on the
      particle size, particle size-distribution and roundness were investigated in case
      of glycine crystallization. Three types of crystallization methods were applied
      according to the solubility results of the substance. In case of cooling
      crystallization, the effect of cooling and stirring rates were investigated. The
      feeding and stirring rates were changed in the feeding crystallization. In the
      antisolvent technique, the effect of cycle and amplitude of the sonification were
      studied on the particle size. A 3(2) full factorial design was applied for
      investigation of the effect of crystallization parameters. The results were
      analyzed by statistical software. The particle size distribution and roundness
      were measured by laser diffraction and light microscopic image analysis systems.
      The polymorph type of products was investigated by XRPD. The crystallized product
      morphology was examined using scanning electron microscopy. We found that the
      crystallization methods and certain parameters have significant effect on the
      particle size, particle size distribution. In spite of the modified particle
      size, morphology, roundness, the polymorph type of the product was the same with
      the original material.

PMID- 22870779
TI  - [Modified release intra-articular drug delivery systems].
AB  - Beside the many advantages of intraarticular formulations (e.g., the systemic
      side effects are kept away), there is a big drawback. During the injections,
      there is the risk for infection therefore the number of injections in a year
      should be reduced. Also a long-term drug exposure should be achieved with an
      injection, and if it is possible, a combination of active ingredients should be
      used. At present there are only formulations with hyaluronic acid or
      glucocorticoid on the market. One of these formulations, a liposomal preparation,
      is of sustained drug release. Many different active ingredients could have a long
      term drug exposure with carrier systems like micro- and nanoparticles, liposomes,
      hydrogels and physically activated delivery systems (thermoresponsive or
      magnetically modulated). The present paper gives an overview about these carrier
      systems, the novel scientific results and the aim of the future researches, as
      well.

PMID- 22870780
TI  - [Osteoporosis and pharmaceutical care].
AB  - The increasing prevalence of osteoporosis is causing a substantial health burden.
      Compliance and adherence to osteoporosis management are of high priority, having
      a significant effect on the cost effectiveness of therapy. In this study, we
      aimed to summarize the literature on patient compliance in osteoporosis. Our
      findings indicate that 60% of the patients have some medication related problem,
      in particular, it is difficult to influence the patients to play an active role
      in their disease management and to keep a high level of persistence.
      Pharmaceutical care could help to reach optimal cooperation between patients and
      the heath care professional, as one of its main objective is to improve the rate
      of patient adherence in long-term drug therapy.

PMID- 22870781
TI  - [Taste-masking possibilities in solid dosage forms].
AB  - Increasing number of new, innovative pharmaceutical products are in the generic
      market. One of the important dosage forms is the group of orally disintegrating
      products. The feature of these products is that they disintegrate rapidly in the
      mouth upon contact with the saliva; therefore the dissolution of the water
      soluble components begins in the mouth. Since a large part of the drug molecules
      is characterised by a more or less bitter taste, even a small amount of the
      dissolved drug can cause an unpleasant taste in the mouth. Manufacturers apply
      different techniques to mask the bitter taste of these products, depending on the
      characteristics of the dosage form and the bioavailability requirements. In this
      study, we reviewed the most widespread taste-masking methods based on the
      scientific literature and different patents and the characteristics of some
      important excipients, and outline an instrumental technique used for bitterness
      measurements.

PMID- 22870782
TI  - Serrated lesions of the colorectum, a new entity: what should a clinician/
      endoscopist know about it ?
AB  - Serrated polyps of the colorectum have received much attention in recent
      literature. Several classifications have been proposed and created considerable
      confusion. Morphology and molecular biology have greatly contributed to the
      better identification of these entity. The recently published WHO classification,
      proposed using the term of "serrated polyp" as a generic term and defined
      sporadic serrated polyps as "a heterogeneous group" of lesions characterized
      morphologically by a serrated (sawtooth or stellate) architecture of the
      epithelial component which include hyperplastic polyps (HP), sessile serrated
      adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA). With the
      development of molecular biology, it is now clear that the serrated pathway is
      one of the new carcinogenic pathways in the colon. There is now strong evidence
      that some serrated polyps correspond to precursors of some sporadic colorectal
      cancer (CRC). The aim of this article is to summarize the present data concerning
      the morphological and molecular characteristics of these serrated lesions and to
      give some recommendations for the management of such lesions.

PMID- 22870783
TI  - Familial primary biliary cirrhosis: like mother, like daughter?
AB  - The reasons underlying why autoimmune diseases overwhelmingly affect women more
      than men are not clear. Nor are the reasons why autoimmune disease is more
      prevalent in families. This review uses primary biliary cirrhosis (PBC) as a
      model autoimmune disease to discuss the familial risk, focusing mainly on mother
      daughter pairs. PBC is a chronic cholestatic liver disease characterised by an
      immune-mediated inflammatory destruction of the small intrahepatic bile ducts,
      with fibrosis progressing to cirrhosis and subsequent liver failure.
      Epidemiological studies have demonstrated that first degree relatives of PBC
      patients are at higher risk of developing PBC, as well as other autoimmune
      diseases. This is especially true for the mothers, daughters and sisters of PBC
      patients. Multiple case reports have highlighted the complexity of mother
      daughter pairs in PBC, and the need for follow-up of these individuals when one
      member of the pair is diagnosed with PBC. It may be the case that diagnosis in
      one individual may lead to early diagnosis in the other, even if they are
      asymptomatic. Early management of PBC may improve the prognosis in these
      patients. This review will examine the literature surrounding PBC in mothers and
      daughters.

PMID- 22870784
TI  - Molecular changes in pancreatic cancer: implications for molecular targeting
      therapy.
AB  - Pancreatic ductal adenocarcinoma has a high mortality rate, which is generally
      related to the initial diagnosis coming at late stage disease combined with a
      lack of effective treatment options. Gemcitabine has been the most commonly used
      drug over the past decade and is still the cornerstone of therapy in adjuvant and
      metastatic settings. Intrinsic or acquired resistance of tumours to gemcitabine
      is, however, a major clinical problem. New therapeutic strategies are urgently
      needed whereas we also need to identify new prognostic and predictive biomarkers.
      This article focuses on gemcitabine resistance, on the role of chemokines and
      chemokine receptors in pancreatic carcinoma initiation and progression, and on
      stellate cells as partners in crime with neoplastic epithelial cells.

PMID- 22870785
TI  - Factors influencing the prognosis of patients with intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND AND AIMS: The outcome of surgical treatment of patients with
      intrahepatic cholangiocarcinoma (ICC) is poor. This study was designed to analyze
      prognostic factors following surgical treatment for ICC. PATIENTS AND METHODS: A
      structured telephone interview was conducted in 132 patients who were surgically
      treated for ICC. Fifteen clinical and pathological factors that may influence
      post-operative survival were analyzed by using Cox proportional hazards model.
      RESULTS: The accumulative 1-, 3-, 5-year survival rate of the 132 patients was
      51.3%, 21.6%, and 11.8% respectively. The mean survival time in patients with
      elevated serum carbohydrate antigen (CA) 19-9 at the time of the operation was
      shorter than in patients with normal serum CA19-9 (9.6 +/- 24.7 vs 16.1 +/- 6
      months, P < 0.01). The median survival time in patients with well-differentiated
      carcinoma was longer than in those with poorly differentiated ICC (23.9 +/- 7.8
      vs. 11.2 +/- 5.0 months, P < 0.01). Patients who were treated with hepatectomy
      and lymph node dissection had a longer survival time than those treated with
      hepatectomy only (16.0 +/- 5.8 vs 10.2 +/- 3.6 months, P < 0.01). Multivariate
      analysis showed that mode of surgical treatment, lymph node metastasis, serum
      level of CA 19-9 and pathological differentiation grade of ICC predicted
      postoperative survival. CONCLUSIONS: Hepatectomy with lymph node dissection is
      associated with an improved survival for patients with ICC. This strategy may be
      recommended for the surgical treatment of ICC.

PMID- 22870786
TI  - Small bowel metastases from melanoma: does videocapsule provide additional
      information after FDG positron emission tomography?
AB  - Finding small bowel metastases of melanoma can be important because surgical
      removal of unique small bowel metastasis of melanoma could improve survival. In
      this study, we evaluated if capsule endoscopy provides additional information
      after Pet CT has been performed. In this series of 9 patients collected from 3
      university centers, capsule endoscopy influenced the therapeutic decision (to
      perform or not a surgical segmental resection) in 2/9 patients. All metastatic
      lesions were found in the proximal bowel. Capsule identified jejunum metastases
      in one case while Pet CT was negative, and identified metastases while Pet CT
      result was not conclusive. In one case PET CT identified mesenteric metastases
      while capsule was negative. SBCE influenced therapeutic decision in 2/9 patients
      concerning the decision of performing small bowel resection or not. In 1 patient
      SBCE changed the stage of the disease without affecting medical therapeutic
      strategy. The prognosis of patients with positive PET and/or capsule findings is
      very limited (2/3 died within the year). In selected patients, capsule endoscopy
      can provide complementary information once PET CT has been performed.

PMID- 22870787
TI  - Association between single nucleotide polymorphisms of the transient receptor
      potential vanilloid 1 (TRPV-1) gene and patients with irritable bowel syndrome in
      Korean populations.
AB  - BACKGROUND AND STUDY AIMS: Transient receptor potential vanilloid type 1 (TRPV1)
      plays a crucial role in pain perception and its expression is up-regulated in
      patients with irritable bowel syndrome (IBS). The aim of this study was to
      investigate the potential association between Single nucleotide polymorphism
      (SNPs) of the TRPV-1 gene and patients with IBS. PATIENTS AND METHODS: We chose
      to focus on three SNPs in the human TRPV1 coding region (rs222749, rs9894618 and
      rs222747) in 80 healthy controls and 103 IBS patients. We developed the high
      resolution melting (HRM) method to determine the genotyping of rs222747 and
      rs9894618 and the genotyping of rs222749 was also determined by direct sequencing
      method. RESULTS: The CG genotype of rs222747 was 58.8% in controls and 45.6% in
      the IBS group. The GG genotype of rs222747 was 15.0% in controls and 20.4% in the
      IBS group. The CT genotype of rs222749 was 313% in controls and 32.0% in the IBS
      group. The CC genotype of rs9894618 was 98.8% in controls and 100.0% in the IBS
      group. There was no significant difference in allele frequency of these three
      SNPs of the TRPV1 gene between controls and the IBS group. Also, no significant
      difference was observed between the IBS subtypes. CONCLUSIONS: These results
      suggest that the SNPs of the TRPV1 gene may not be associated with IBS in Korean
      populations. Further studies with large cases are needed to validate the results
      of the present study.

PMID- 22870788
TI  - Expression of IFNAR2 mRNA in peripheral blood mononuclear cells of patients with
      HCV infection.
AB  - BACKGROUND: To investigate the differences of interferon-alpha/beta receptor 2
      (IFNAR2) mRNA expression level in peripheral blood mononuclear cells (PBMCs)
      between different stages of hepatitis C virus (HCV) infection and to determine
      the correlation with the effectiveness of interferon therapy. METHODOLOGY: 58
      patients, positive for anti-HCV antibodies, were divided into three groups
      depending on their clinical symptoms: acute hepatitis (4 cases), chronic
      hepatitis (46 cases) and liver cirrhosis (8 cases). 15 volunteers served as
      healthy controls. PBMCs were purified by density gradient centrifugation and
      IFNAR2 mRNA was amplified from these cells by a reverse transcription-polymerase
      chain reaction (RT-PCR) assay. RESULTS: The detection rate of IFNAR2 mRNA was
      87.9% (51/58 cases) in the PBMCs of patients with HCV infection, significantly
      higher than that in the control group (333%, 5/15 cases; P < 0.05). While the
      positive rate was 93.5% (43/46 cases) in the chronic hepatitis group, which was
      significantly higher than that in the liver cirrhosis group (50%, 4/8 cases; P <
      0.05). Furthermore, there is no significant difference in the positive rates for
      HCV-RNA of PBMCs among groups (P > 0.05). The positive rate of IFNAR2 mRNA in
      PBMCs was not correlated with the viral load of HCV-RNA in serum (P > 0.05).
      However, higher expression of IFNAR2 mRNA in the PBMCs did correlate with the
      effectiveness of interferon therapy (P < 0.05). CONCLUSIONS: HCV infection up
      regulates the expression of IFNAR2 mRNA in PBMCs. IFNAR2 mRNA expression in the
      chronic hepatitis group was higher than that in the liver cirrhosis group, and
      significantly correlated with the effectiveness of interferon therapy, which was
      independent of the viral load.

PMID- 22870789
TI  - Nitric oxide donor drugs improve the distribution and engraftment of transplanted
      hepatocytes in the liver.
AB  - BACKGROUND: Hepatocyte transplantation could be an alternative to liver
      transplantation for the treatment of metabolic diseases, however this therapy is
      still limited by the loss of transplanted cells in the portal radicles before
      their entry into the sinusoids to engraft. Therefore, we investigated the effect
      of glyceryl trinitrate on hepatic sinusoids and on the efficacy of cell
      engraftment in a syngenic mice model. METHODS: We first assessed the effect of
      GTN portal infusion on the parenchymal spreading of colored microspheres.
      Hepatocytes transplantation in a syngenic mice model was then performed
      concomitantly with GTN infusion. The distribution of transplanted hepatocytes and
      their ultimate engraftment were analysed. RESULTS: After GTN perfusion 27% of
      microspheres shifted from the portal to the sinusoidal zone. Transplanted
      hepatocytes distribution changed significantly in the portal and parenchymal
      zones from respectively 53 +/- 2% and 46.8 +/- 2% in control animals to 32.5 +/-
      2.4% and 67.5 +/- 2.4% in GTN-treated animals. At days 7 and 15, we noted a
      significantly better engraftment in GTN group vs. controls (60 +/- 4 vs. 37 +/- 2
      transplanted hepatocytes in 20 fields x 400). CONCLUSIONS: Portal perfusion of
      GTN improved the access of microspheres and transplanted hepatocytes to the
      sinusoidal bed and also improved the percentage of cell engraftment in the liver.
      These results suggest that drug dilatation of portal pedicles prior to
      transplantation increases the efficiency of hepatocyte grafting.

PMID- 22870790
TI  - Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Preliminary evidence suggests that inhibition of dipeptidyl
      peptidase (DPP)-IV preserves pancreatic beta cell function in patients with type
      2 diabetes (T2D). However, its effects on liver histology in nonalcoholic
      steatohepatitis (NASH), hepatic complication of diabetes, have not yet been
      adequately explored. The present open-label, single-arm observational pilot study
      investigated the effects of one year of treatment with a dipeptidyl peptidase-IV
      inhibitor, sitagliptin, on liver histology, body mass index (BMI), and laboratory
      parameters in NASH patients with T2D. PATIENTS AND METHODS: Paired liver biopsies
      from 15 diabetic patients with NASH (7 males, 8 females; mean age: 49.7 +/- 8.1
      years (range: 36-62)) before and after one year of therapy with sitagliptin 100
      mg once daily were studied. Clinical and laboratory parameters were recorded.
      RESULTS: Treatment with sitagliptin resulted in a significant decrease in
      ballooning (P = 0.014) and NASH scores (P = 0.04), while the reduction in the
      steatosis score was of borderline statistical significance (P = 0.054). These
      effects were accompanied by a significant reduction in body mass index, AST, and
      ALT levels. CONCLUSION: Our study suggests that sitagliptin ameliorates liver
      enzymes and hepatocyte ballooning in NASH patients with T2D and may have
      therapeutic implications.

PMID- 22870791
TI  - Update of the Belgian Association for the Study of the Liver guidelines for the
      treatment of chronic hepatitis C genotype 1 with protease inhibitors.

PMID- 22870792
TI  - Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare
      association.
AB  - Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by
      the presence of innumerable small discrete nodules involving a variable segment
      of the gastrointestinal tract. The association between nodular lymphoid
      hyperplasia and other benign and malignant diseases has been clearly described,
      with an increased risk of gastrointestinal tumours, namely gastrointestinal
      lymphoma. However, the association with extraintestinal lymphoma seems extremely
      rare. The authors present a clinical case of a patient with nodular lymphoid
      hyperplasia of the small and large intestine that subsequently developed an
      extraintestinal lymphoma (diffuse large B-cell lymphoma).

PMID- 22870793
TI  - Focal parietal necrosis of the sigmoid due to atypical neuroleptics: a case
      report.
AB  - We present the case of a 26-year-old man with schizoid personality disorder who
      suffered from a very focal and transparietal necrosis of the sigmoid after an
      overdose of atypical neuroleptics. This is a singular, rather unknown and
      potentially lethal side effect of these drugs. The physiopathology of this
      complication is multifactorial.

PMID- 22870794
TI  - Dysphagia lusoria caused by a right-sided aorta.
AB  - We report a case of an 80-year-old female with dysphagia lusoria caused by
      oesophageal compression by a right-sided atheromatous aorta. The relationship
      between aortic root vascular anomalies and dysphagia has been clearly established
      in literature and can be diagnosed by a barium swallowing study, followed by CT
      or MRI. Aortic anomalies and variations in aortic branches are caused by
      embryonic malformations and are mostly described in association with congenital
      heart lesions. In this pauci-symptomatic patient, the preferred treatment is a
      conservative management.

PMID- 22870795
TI  - Lanreotide treatment of metastatic hepatocellular carcinoma resulting in partial
      regression and more than 3 years of progression-free survival.
AB  - We describe the case of a 54 years old woman, with hepatitis B, in whom the
      diagnosis of a 6 cm hepatocellular carcinoma (HCC) in the left liver was made in
      2001. Alpha-foeto-protein (AFP) was 63 ng/mL (NI < 10 ng/mL). After work-up
      including liver and tumor biopsy confirming HCC and only fibrosis in the
      nontumoral liver, left hepatectomy was performed. Final pathology showed a well
      differentiated HCC with tumoral portal vein thrombosis. Unfortunately, lung and
      mediastinal adenopathies were detected by CT scan 17 months later. Mediastinal
      nodes were punctured by endosonographic ultrasound, confirming HCC. The patient
      started treatment with Lanreotide 30 mg twice a month (Somatuline PR, Ipsen).
      Three months later, CT showed decrease in size of the mediastinal nodes and
      complete disappearance of the lung nodes. This objective response lasted for 42
      months. The treatment was without any significant side effect. Retrospectively,
      immunohistochemistry was performed to detect somatostatine receptors (sstr) 2.
      Both the primary tumor and the node showed intense membranous and cytoplasmic
      staining for sstr2. In 2006, AFP rose and CT showed the appearance of a new
      mediastinal node. At that time, octreoscan was performed and showed uptake in the
      new node, although insufficient for metabolic radiotherapy. This case suggests
      that, although a number of randomized controlled trials did not show a benefit of
      somatostatin analogues in the treatment of advanced HCC, a subset of patients
      could benefit from treatment provided their tumor expresses sstr2, on which the
      existing drugs are efficient.

PMID- 22870796
TI  - A rare complication of Henoch-Schonlein Syndrome: gastrointestinal infarction and
      perforation.

PMID- 22870797
TI  - A rare complication of percutaneous endoscopic gastrojejunostomy (PEG-J):
      duodenal bulb perforation due to retrograde migration.

PMID- 22870798
TI  - Synchronous hepatocellular carcinoma and sigmoid colon metastasis presenting as
      liver and intra-abdominal abscesses.

PMID- 22870799
TI  - Dilation of a severe biliary stricture by using a guidewire left in place
      overnight.

PMID- 22870800
TI  - Combined endoscopic sphincterotomy and trans-catheter arterial embolization for
      the treatment and prevention of acute pancreatitis induced by hemobilia from
      hepatocellular carcinoma.

PMID- 22870801
TI  - Characterization of a new cold-adapted lipase from Pseudomonas sp. TK-3.
AB  - A psychrotrophic Pseudomonas sp. TK-3 was isolated from dirty and cool stream
      water in Toyama, Japan from which we cloned and characterized the bacterial
      lipase LipTK-3. The sequenced DNA fragment contains an open reading frame of
      1,428 bp that encoded a protein of 476 amino acids with an estimated molecular
      mass of 50,132 Da. The lipase showed high sequence similarity to those of
      subfamily Iota.3 lipase and had a conserved GXSXG motif around the catalytic Ser
      residue. Its optimal temperature was 20-25  degrees C, lower than in most other
      subfamily Iota.3 lipases. The lipase exhibited about 30 % of maximal activity at
      5  degrees C. The optimal pH value was 8.0. The activity was strongly inhibited
      by EDTA and was highly dependent on Ca(2+). Tricaprylin and p-nitrophenyl
      caprylate were the most favorable substrates among the triglycerides and p
      nitrophenyl esters, respectively. LipTK-3 also showed high activity towards
      natural substrates including edible vegetable oils and animal fats. Furthermore,
      LipTK-3 was very active and stable in the presence of several detergents, metal
      ions, and organic solvents. This cold-adapted lipase may prove useful for future
      applications.

PMID- 22870802
TI  - First-in-class antifibrotic therapy targeting type 1 lysophosphatidic acid
      receptor.
AB  - Fibrosis is a normal process for repairing injured tissue. However, aberrant or
      hyperfibrotic responses result in serious pathologic conditions and sometimes
      life-threatening diseases. A new class of drugs antagonizing type 1
      lysophosphatidic acid receptor has been developed and is under investigation in
      clinical trials for the treatment of idiopathic pulmonary fibrosis and systemic
      fibrosis or scleroderma. This will be the first drug in its class to target G
      protein-coupled receptors for lysophosphatidic acid.

PMID- 22870803
TI  - Synthesis and cytotoxicity of novel 2,2'-bis- and 2,2',2"-tris-indolylmethanes
      based bengacarboline analogs.
AB  - Tungstosilicic acid hydrate was employed as an efficient catalyst for the
      synthesis of bisindolylmethanes 4 using the Friedel-Crafts reaction of N-sulfonyl
      tryptamine 5 with various aromatic aldehydes, except 3-formylindole. In the
      excluding case, tris-indolylmethane 7 was formed via a sequential addition
      elimination-addition process. The bioactivity test revealed that the phenolic
      hydroxyl group plays an important role in cytotoxicity; it demonstrated that
      ortho- and para-hydroxy bis-indolylmethane (BIM) analogs (4b and 4d) displayed
      cytotoxic potency toward HepG2 (human hepatocellular liver carcinoma cell line)
      and MOLT-3 (human lymphoblastic leukemia cell line) cancer cell lines.
      Significantly, both analogs showed slightly higher inhibitory efficacy than the
      control drug, etoposide, in HepG2 cells, and the analog 4d exhibited the most
      potent activity against MOLT-3 cell lines, with an IC(50) value of 1.62 MUg/mL.

PMID- 22870804
TI  - Synthesis, antimicrobial, and antiviral activities of some new 5-sulphonamido-8
      hydroxyquinoline derivatives.
AB  - A series of fused pyranopyrazole and pyranoimidazole, namely 5-(3,6-diamino-4
      aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-2-yl)sulphonyl-8-hydroxyquinolines (5a
      e), 5-(6-amino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-3-yl)sulphonamido-8
      hydroxyquinolines (6a-e), 5-(2-thioxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3
      d)imidazol-2-yl)sulphonyl-8-hydroxyquinolines (10a-e), and 5-(2-oxo-4-aryl-5
      carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl) sulphonyl-8-hydroxyquinolines
      (11a-e), have been prepared via condensation of some arylidine malononitriles
      with 5-sulphonamido-8-hydroxyquinoline derivatives 3, 4, 8 and 9. All the
      synthesized compounds were screened for their antimicrobial activities, and most
      of the tested compounds showed potent inhibition growth activity towards
      Escherichia coli, Pseudomonas aeruginosa (Gramnegative bacteria). Furthermore,
      six selected compounds were tested for their antiviral activity against avian
      paramyxovirus type1 (APMV-1) and laryngotracheitis virus (LTV), and the results
      showed that a concentration range of 3-4 MUg per mL of compounds 2, 3, and 4
      showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture
      infected dose fifty (TCID(50)) and LTV of 500 TCID(50) in Vero cell cultures
      based on their cytopathic effect. Chicken embryo experiments show that compounds
      2, 3, and 4 possess high antiviral activity in vitro with an inhibitory
      concentration fifty (IC(50)) range of 3-4 MUg per egg against avian APMV-1 and
      LTV and their toxic concentration fifty (CC(50)) of 200-300 MUg per egg.

PMID- 22870805
TI  - Antitumor activity of novel pyridine, thiophene and thiazole derivatives.
AB  - 2-Cyano-N'-[1-(2,5-dimethoxyphenyl)]ethylideneacetohydrazide 1 was obtained via
      reaction of cyanoacetic acid hydrazide with 2,5-dimethoxyacetophenone. A number
      of novel pyridines 2a-j, 3, 4, thiophenes 5-9 and thiazoles 10-12 were prepared
      by using the hydrazide-hydrazone derivative 1 as a starting material. The
      structure of the newly synthesized compounds was characterized by elemental
      analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All the target
      compounds were subjected to in vitro antitumor activity against Ehrlich ascites
      carcinoma (EAC) cells. Compounds 2j and 6 showed a higher activity with IC(50)
      values (54.54, 61.57 MUM), 8 when compared with a reference drug IC(50) value
      (68.99 MUM), while compound 5 is nearly as active as doxorubicin (CAS 23214-92
      8).

PMID- 22870806
TI  - Arylazolyl(azinyl)thioacetanilide. Part 9: Synthesis and biological investigation
      of thiazolylthioacetamides derivatives as a novel class of potential antiviral
      agents.
AB  - In continuation of our endeavor to develop new, potent, selective and less toxic
      antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl)
      thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route
      and evaluated for their anti-HIV activities against wild-type virus and
      clinically relevant mutant strains, and for their anti-influenza virus activities
      against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The
      selected active compounds were also assayed for their enzymic inhibitory
      activities. The results showed that some 2-chloro substituted
      thiazolylthioacetamide derivatives possessed potent activity against wild type
      HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells
      with EC(50) values in micromolar range. Two 2-amino substituted thiazole
      derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in
      MDCK cells with EC(50) values much lower than that of oseltamivir carboxylate,
      ribavirin, amantadine and rimantadine. Though the mechanism of actions is still
      unclear, these novel thiazolylthioacetamides might serve as original leads for
      further pharmacological investigations as potential therapeutic agents against
      HIV-1 or influenza virus.

PMID- 22870807
TI  - Anticancer activity of novel indenopyridine derivatives.
AB  - Eighteen new 4-[2-amino-3-cyano-5-oxo-4-substitutedaryl-4H-indeno[1,2-b]pyridin-1
      (5H)-yl]benzenesulfonamide derivatives 6a-q were synthesized via a reaction of
      aromatic aldehydes, enaminone 3 and malononitrile in one-pot reaction. Also,
      compounds 6a-q were obtained, via another route by reaction of enaminone 3 with
      arylidenemalononitriles 4a-q. The structure of the synthesized compounds was
      characterized by microanalysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data.
      All the target compounds were subjected to in vitro anticancer activity against
      breast cancer cell line (MCF7). Compound 6d showed a higher potency with IC(50)
      value (4.34 MUM) than that of the doxorubicin (5.40 MUM), as the reference drug,
      while compound 6n with IC(50) value (6.84 MUM) is nearly as active as
      doxorubicin. Also, compounds 6a-c, 6e, 6f, 6h and 6p exhibited a moderate
      activity, while compounds 3, 6g, 6i-m, 6o and 6q showed weak activity.

PMID- 22870808
TI  - Synthesis and biological evaluation of novel pyrazoline derivatives as anti
      inflammatory and antioxidant agents.
AB  - A series of novel 5-aryl-3-cyclopropyl-4,5-dihydropyrazole derivatives 2a-p were
      synthesized via cyclization of chalcones 1a-h with thiosemicarbazide or
      semicarbazide HCl and evaluated as anti-inflammatory/antioxidant agents. The
      structures were confirmed by elemental analyses and spectral data. The free
      radical scavenging activity toward superoxide was determined. Their effect on
      hepatocytes viability and nitric oxide (NO) production in LPS-stimulated
      macrophages was also determined. The results showed that compounds 2e and 2n
      demonstrated the highest free-radical scavenging and anti-inflammatory
      activities, thus can be useful in the prevention of oxidative stress and
      inflammation-related disorders.

PMID- 22870809
TI  - Anticomplementary activity of oleanane-type triterpenes from the roots of
      Aceriphyllum rossii.
AB  - To gain a better understanding of the anticomplement activity of triterpenoids,
      the complement activity of five unusual oleanane-type triterpenoids, bearing a
      carboxyl group at the C-29 position, were estimated against the classical pathway
      of a complementary system. The five triterpenoids were obtained from the roots of
      Aceriphyllum rossii (Saxifragaceae), and were determined to be aceriphyllic acids
      B-E (1-4) and K (5). Of the isolated compounds, compounds 1, 2 and 5 showed
      anticomplement activities, with IC(50) values of 328.4, 77.5 and 348.6 MUM,
      respectively, whereas, compounds 3 and 4 were inactive. This showed that a
      carboxyl group at the C-23 position and an alpha-configuration of a hydroxyl
      group at the C-3 position in the olean-29-carboxylic acid triterpenoids seemed to
      play an important role in the anticomplement activity of human serum against
      erythrocytes.

PMID- 22870810
TI  - Evaluation of some classical hydrazones of ketones and 1,2-diketones as
      antileishmanial, antibacterial and antifungal agents.
AB  - The paper describes the synthesis and antimicrobial (antileishmanial,
      antibacterial and antifungal) activity of some classical hydrazones of
      benzophenones and of 1,2-diketones. N-(Diaryl) acyl derivatives of these
      hydrazones have also been synthesized and evaluated. 4,4,-Demthoxybenzil
      monohydrazone and 4,4'-dimethoxybenzophenone hydrazone showed significant
      antileishmanial activity. The effect of substituents on the bioactivity is
      discussed.

PMID- 22870811
TI  - A convenient method for the enantiomeric separation of alpha-amino acid esters as
      benzophenone imine Schiff base derivatives.
AB  - A convenient liquid chromatographic method for the separation of alpha-amino acid
      esters as benzophenone Schiff base derivatives on coated chiral stationary phases
      (CSPs) (Chiralcel OD-H, Chiralcel OD, Chiralpak AD-H, Chiralpak AD, and Chiralpak
      AS) or covalently immobilized CSPs (Chiralpak IA, Chiralpak IB, and Chiralpak IC)
      derived from polysaccharide derivatives is described. Benzophenone imine
      derivatives of alpha-amino acid esters were readily prepared by stirring
      benzophenone imine and the hydrochloride salts of alpha-amino acid esters in 2
      propanol. The chromatographic separations were conducted at a flow rate 1.0
      mL/min and a detection wavelength of 254 nm; 0.5% 2-propanol/hexane (v/v) was
      used on CSPs. In general, the resolution of Chiralpak IC was superior to those of
      the other CSPs. In addition, the resolutions of other arylimine derivatives of
      alpha-amino acid esters and the effects of different mobile phases on the
      enantiomeric separation of alpha-amino acid esters as benzophenone imine
      derivatives on Chiralpak IC were investigated.

PMID- 22870812
TI  - Inhibitory activity of coumarins from Artemisia capillaris against advanced
      glycation endproduct formation.
AB  - Since glycation can lead to the onset of diabetic complications due to chronic
      hyperglycemia, several indigenous Artemisia species were evaluated as potential
      inhibitors of advanced glycation endproducts (AGE). Among them, the Artemisia
      capillaris plant demonstrated the highest AGE inhibitory activity. Repeated
      column chromatography was performed to isolate a new acylated flavonoid
      glycoside, acacetin-7-O-(6"-O-acetyl)-beta-D-glucopyranosyl-(1->2)[alpha-L
      rhamnopyranosyl]-(1->6)-beta-D-glucopyranoside, along with 11 known flavonoids
      (acacetin-7-O-beta-D-glucopyranosyl-(1->2)[alpha-L-rhamnopyranosyl]-(1->6)-beta-D
      glucopyranoside, linarin, quercetin, hyperoside, isorhamnetin, isorhamnetin 3
      galactoside, isorhamnetin 3-glucoside, isorhamnetin 3-arabinoside, isorhamnetin 3
      robinobioside, arcapillin, and cirsilineol), six coumarins (umbelliferone,
      esculetin, scopoletin, scopolin, isoscopolin, and scoparone), and two phenolic
      derivatives (4,5-di-O-caffeoylquinic acid and chlorogenic acid). In determining
      the structure-activity relationship (SAR), it was found that the presence and
      position of hydroxyl group of test coumarins (coumarin, esculin, isoscopoletin,
      daphnetin, 4-methylcoumarin, and six isolated coumarins) may play a crucial role
      in AGE inhibition. A free hydroxyl group at C-7 and a glucosyl group instead of a
      methoxyl group at C-6 are two important parameters for the inhibitory potential
      of coumarins on AGE formation. A. capillaris and five key AGE inhibitors,
      including 4,5-di-Ocaffeoylquinic acid, umbelliferone, esculetin, esculin, and
      scopoletin, were identified as potential candidates for use as therapeutic or
      preventive agents for diabetic complications and oxidative stress-related
      diseases. We understand this to be the first detailed study on the SAR of
      coumarins in AGE inhibition.

PMID- 22870813
TI  - Lipid emulsion as a drug delivery system for breviscapine: formulation
      development and optimization.
AB  - In this study, we developed an optimized formulation of a breviscapine lipid
      emulsion (BLE) and evaluated the physicochemical properties and in vivo
      pharmacokinetics of BLE in rats. For the preparation of the lipid emulsion,
      soybean oil and oleic acid were used as the oil phase, lecithin and poloxamer 188
      as surfactants and glycerol as co-surfactant. An optimized formulation consisting
      of soybean oil (10.0%), oleic acid (0.9%), lecithin (1.5%), poloxamer 188 (0.4%),
      and glycerol (2.25%) was selected. The results showed that the average particle
      size, polydispersity index, and zeta potential of the optimized formulation were
      183.5 +/- 5.5 nm, 0.098 +/- 0.046, and -35.0 +/- 2.5 mV, respectively. The BLE
      was stable for at least three month at room temperature. After a single
      intravenous dose of 4 mg/kg to rats, the AUC of scutellarin from the lipid
      emulsion was about 1.5-fold higher than that of the commercial product
      (breviscapine injection). In conclusion, the optimized formulation of BLE showed
      positive results over the commercial product in terms of the physicochemical
      properties and pharmacokinetics of BLE in rats.

PMID- 22870814
TI  - Discrimination of Phellodendron amurense and P. chinense based on DNA analysis
      and the simultaneous analysis of alkaloids.
AB  - Phellodendri Cortex is the bark of the stems of Phellodendron amurense Ruprecht
      or P. chinense Schneider (Rutaceae), which is orginated from periderm. The
      internal transcribed spacer sequences of 20 originated plants and identified
      samples were analyzed. The result showed that the 99% of the base sequences of P.
      amurense were identical to that of P. chinense, but the differentiation of P.
      amurense and P. chinense was difficult. In addition, the ribulose-1, 5
      bisphospate carboxylase large subunit (rbcL) intergenic spacer sequences of
      specific parts produced the same result. However, when the analysis was carried
      out by using the RAPD (randomly amplification polymorphism DNA) analysis method,
      which utilizes 48 randomly primers, it allowed us to confirm the polymorphism of
      P. amurense and P. chinense in 12 primers. A high-performance liquid
      chromatographic (HPLC) method was developed and validated for the simultaneous
      quantitation of berberine, palmatine and jatrorrhizine in a traditional herbal
      drug, Phellodendri Cortex. The HPLC method was applied successfully to the
      quantification of three constituents in the extract of twenty Phellodendri
      Cortex. The results indicated that the established HPLC and RAPD methods are
      suitable for the quantitative analysis and the quality control multi-simultaneous
      discrimination in Phellodendri Cortex.

PMID- 22870815
TI  - Effects of furanocoumarins in Kampo extract-based medicines on rat intestinal
      absorption of CYP3A and P-glycoprotein substrate drugs in vivo.
AB  - While a great deal of information of drug-drug interactions is known, most
      concern Western drugs. Relatively little is known of the interactions between
      Western drugs and traditional drugs such as Kampo extract medicines (Japanese
      medicines modified from traditional Chinese medicines). This study investigated
      the effects of the marketed Kampo extract medicines, Senkyu-cha-cho-san and Sokei
      kakketsu-to, on the intestinal absorption of CYP or P-glycoprotein (P-gp) in
      vivo. Midazolam, a CYP3A substrate drug, or talinolol, a P-gp substrate drug, was
      orally administered to rats with each of these Kampo extract medicines. Senkyu
      cha-chosan or Sokei-kakketsu-to administered as a standard regimen did not
      obviously affect Cmax and area under the curve (AUC) of midazolam, although both
      Kampo extract medicines contained notopterol, a potent CYP3A4 inhibitor in vitro.
      The results implied a lack of potent drug-drug interactions between both Kampo
      extract medicines and CYP3A substrate drugs. Concomitant administration of each
      Kampo extract medicine unexpectedly showed the tendency to decrease Cmax and AUC
      of talinolol. Decreased intestinal absorption of talinolol might be caused, not
      by the inhibition of P-gp, but by the inhibition of organic anion transporting
      peptides by both Kampo extract medicines.

PMID- 22870816
TI  - In vitro evaluation of antibacterial activities and anti-inflammatory effects of
      Bifidobacterium spp. addressing acne vulgaris.
AB  - The objective of this study was to evaluate the antibacterial and anti
      inflammatory effect of Bifidobacterium spp. In the first part of the study, the
      antibacterial activities of live and sonicated cells, from a total of 23
      Bifidobacterium species, on the growth of 5 different strain of Staphylococcus
      aureus. Six strains, of sonicated Bifidobacterium, exhibited antibacterial
      activity against staphylococci samples, and seven Bifidobacterium strains
      exhibited antibacterial activity on the growth of S. aureus S.P.-N2. In the
      second part of the study, we tested the antimicrobial activity, of
      Bifidobacterium against Propionibacterium acne KCTC3320, using the co-culture
      method. The loss of P. acnes viability, caused by B. adolescentis SPM0308 and B.
      longum SPM1207, was 84% and 75%, respectively (*p < 0.05). In the third part of
      the study, the anti-inflammatory activity of B. adolescentis SPM0308 and B.
      longum SPM1207 were assessed; nitric oxide (NO), and tumor necrosis factor-alpha
      (TNF-alpha), production were tested using the murine macrophage RAW 264.7 cell
      line. Treatment of RAW 264.7 cells, with Bifidobacterium, decreased production of
      NO and TNF-alpha rather than LPS (100 ng/mL) treatment. The results suggest that
      B. adolescentis SPM0308 could be used as an effective control for P. acnes
      KCTC3320, and S. aureus, and reduce the risk of acne vulgaris development. We
      suggest that B. adolescentis SPM0308 may be a useful probiotic microorganism, for
      prevention of acne vulgaris, without adverse effects.

PMID- 22870817
TI  - Effect of beta-glucan originated from Aureobasidium pullulans on asthma induced
      by ovalbumin in mouse.
AB  - The objective of this study is to detect the effect of beta-glucan derived from
      Aureobasidium pullulans SM-2001, a UV induced mutant of A. pullulans on the
      ovalbumin (OVA) induced allergic asthma. The test articles were orally
      administered to OVA-inducing asthmatic mice 4 days after sensitization for 13
      days at 31.25, 62.5 or 125 mg/kg levels. Three days after the OVA sensitization,
      ten mice were selected per group based on body weight and were sacrificed three
      days after the OVA aerosol challenge. The changes on the body weight, lung
      weight, total leukocytes in peripheral blood and total cells in bronchoalveolar
      lavage fluid (BALF) were observed with changes on the lung histopathology and
      histomorphometry. The results were compared with dexamethasone (DEXA) 3 mg/kg
      intraperitoneally treated mice. The results showed increases of body weight after
      the OVA aerosol challenge, lung weight, total leukocytes and eosinophils in
      peripheral blood, total cell numbers, neutrophil and eosinophils in BALF were
      detected in the OVA control compared to sham control (non-OVA). However, these
      changes from asthmatic responses were significantly or dose-dependently decreased
      in the beta-glucan-dosing groups compared to those of the OVA control. Therefore,
      it is concluded that beta-glucan has favorable effects on asthmatic response
      induced by OVA. It was found that beta-glucan 125 mg/kg showed similar or
      slightly lower efficacy compared with DEXA 3 mg/kg.

PMID- 22870818
TI  - Rhamnetin-induced suppression of clonal expansion during early stage of
      adipogenesis.
AB  - Adipocyte differentiation plays a pivotal role in the progression of obesity
      which is a major risk factor for several diseases such as diabetes, hypertension
      and coronary heart disease. In this study, the inhibitory effect of rhamnetin, a
      flavonoid compound, on adipogenesis in 3T3-L1 cells was investigated. Rhamnetin
      decreased the accumulation of lipid droplets, and inhibited the elevation of
      triglyceride content in the adipocytes (IC(50) = 17.3 MUM). The expressions of
      PPARgamma, C/EBPalpha, and perilipin, adipocyte differentiation markers, were
      significantly reduced by rhamnetin. Triglyceride biosynthesis and clonal
      expansion of adipocytes were completely inhibited during the early stage by
      rhamnetin. Additionally, rhamnetin significantly decreased the expression of
      C/EBPbeta, an early stage marker. Our results indicate that suppression of clonal
      expansion during the early stage of adipogenesis by rhamnetin may be associated
      with inhibition of the C/EBPbeta, C/EBPalpha, and PPARgamma pathways.

PMID- 22870819
TI  - The protective effect of rutin against ischemia/reperfusion-associated
      hemodynamic alteration through antioxidant activity.
AB  - Reactive oxygen species exert toxic effects during ischemia-reperfusion (I/R)
      injury of various organs. This study was designed to evaluate the preventive
      effects of various isoflavonoids such as biochanin A, daidzein, genistein, rutin
      and quercetin. These compounds are wellknown naturally occurring compounds with
      beneficial health effects and antioxidant activity. Free radical scavenging
      activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and
      superoxide dismutase (SOD) assay. Among the isoflavonoids tested, biochanine A,
      quercetin and rutin showed significant DPPH free radical scavenging activity.
      Similarly, treatment of biochanine A, genistein and rutin significantly increased
      SOD activity in neonant rat heart myocyte primary cells as well as in H9C2 cells.
      For ex vivo study, hearts from Sprague-Dawley rats were perfused in Langendorff
      apparatus with Krebs-Henseleit solution with a gas mixture of 95% O(2) and 5%
      CO(2). Hearts were subjected to 20 min of pre-ischemia followed by 20 min of
      global ischemia, and then 50 min of reperfusion at 37 degrees C. The test
      compounds were perfused 10 min before ischemia and during the entire reperfusion
      period. Among the isoflavonoids tested, only rutin significantly increased left
      ventricular developed pressure (LVDP) and increased maximum positive and negative
      dP/dt (+/- dP/dtmax). In left ventricular end diastolic pressure (LVEDP)
      analysis, rutin, daidzein and biochanin A were effective. Among the
      isoflavonoids, rutin had consistent protective effects in I/R injury by affecting
      cardiac dynamic factors as well as by enhancing SOD and DPPH activity.

PMID- 22870820
TI  - Protective effect of fucoidan against acetaminophen-induced liver injury.
AB  - Fucoidan, a sulfated polysaccharide extracted from various brown seaweeds,
      possesses a wide range of pharmacological properties. In this study, we
      investigated the protective effect of fucoidan on acetaminophen-induced acute
      liver injury in rats. Liver injury was induced by administration of acetaminophen
      (800 mg/kg, i.p.) and fucoidan was administered (100 mg kg, p.o.) 2 h before and
      after acetaminophen administration. After 24 h, co-treatment of fucoidan
      ameliorated liver damage and cell death induced by acetaminophen. Acetaminophen
      induced the overexpression of CYP2E1, one of the metabolizing enzymes of
      acetaminophen, but cotreatment with fucoidan suppressed its increased expression
      of CYP2E1. Fucoidan also reduced the hepatic apoptosis induced by acetaminophen
      exposure as shown in the protein expression of Bax, Bcl-2, and cleaved caspase-3.
      The anti-oxidative effect of fucoidan was observed from the increase of the
      production and expression of glutathione, superoxide dismutase, and glutathione
      peroxidase, both of which were decreased by acetaminophen. Also, fucoidan
      decreased the expression of inflammatory mediators, including tumor necrosis
      factoralpha, interleukin 1 beta, and inducible nitric oxide synthase. Taken
      together, the data demonstrate the hepato-protective effects of fucoidan against
      acetaminophen-induced liver injury via anti-oxidant, anti-inflammatory, and anti
      apoptotic mechanisms.

PMID- 22870821
TI  - Simplified analysis of lipoprotein lipase activity: evaluation of lipasemic
      activity of low molecular weight heparin in rats.
AB  - A simple procedure for measuring lipoprotein lipase activity was developed by
      using newly formulated substrate with turbidimetry method. The activity of
      lipoprotein lipase was expressed as Y (value) (%) that was calculated by
      measuring UV absorbance (600 nm) at two time points (30 sec and 15 min). Lipid
      emulsions as the substrate and other factors affecting the lipolytic activity of
      lipase were studied. The optimal conditions for an in vitro experiment were found
      to be with LIPOMCT as lipid substrate at 37 degrees C in tris-HCl buffer (pH 7.4)
      in the presence of BSA. To evaluate an in vivo applicability, low molecular
      weight heparin (LMWH)-containing drug, Sulodexide, was administered to the rats.
      The serum from LMWH-administered rats was incubated in an optimized analytical
      condition without BSA. As expected, increasing the amount of LMWH administered
      led to higher lipase activity. The newly developed method was successfully
      applied to an in vivo model suggesting the potential to be applicable for the
      pharmacodynamic studies of commercially available products of LPL analogues in
      human subjects, and for the diagnosis of acute pancreatitis in the clinical
      laboratory.

PMID- 22870822
TI  - Neuroprotection of Ilex latifolia and caffeoylquinic acid derivatives against
      excitotoxic and hypoxic damage of cultured rat cortical neurons.
AB  - Ilex latifolia (Aquifoliaceae), one of the primary components of "Ku-ding-cha",
      has been used in Chinese folk medicine to treat headaches and various
      inflammatory diseases. A previous study demonstrated that the ethanol extract of
      I. latifolia could protect against ischemic apoptotic brain damage in rats. The
      present study investigated the protective activity of I. latifolia against
      glutamate-induced neurotoxicity using cultured rat cortical neurons in order to
      explain a possible mechanism related to its inhibitory effect on ischemic brain
      damage and identified potentially active compounds from it. Exposure of cultured
      cortical neurons to 500 MUM glutamate for 12 h triggered neuronal cell death. I.
      latifolia (10-100 MUg/mL) inhibited glutamate-induced neuronal death, elevation
      of intracellular calcium ([Ca(2+)](i)), generation of reactive oxygen species
      (ROS), the increase of a pro-apoptotic protein, BAX, and the decrease of an anti
      apoptotic protein, BcL-2. Hypoxia-induced neuronal cell death was also inhibited
      by I. latifolia. 3,4-Dicaffeoylquinic acid (diCQA), 3,5-diCQA, and 3,5-diCQA
      methyl ester isolated from I. latifolia also inhibited the glutamate-induced
      increase in [Ca(2+)](i), generation of ROS, the change of apoptosis-related
      proteins, and neuronal cell death; and hypoxia-induced neuronal cell death. These
      results suggest that I. latifolia and its active compounds prevented glutamate
      induced neuronal cell damage by inhibiting increase of [Ca(2+)](i), generation of
      ROS, and resultantly apoptotic pathway. In addition, the neuroprotective effects
      of I. latifolia on ischemia-induced brain damage might be associated with the
      anti-excitatory and anti-oxidative actions and could be attributable to these
      active compounds, CQAs.

PMID- 22870823
TI  - Cadmium-zinc-telluride myocardial perfusion imaging in obese patients.
AB  - We have evaluated the impact of increased body mass on the quality of myocardial
      perfusion imaging using a latest-generation gamma-camera with cadmium-zinc
      telluride semiconductor detectors in patients with high (>=40 kg/m(2)) or very
      high (>=45 kg/m(2)) body mass index (BMI). METHODS: We enrolled 81 patients,
      including 18 with no obesity (BMI < 30 kg/m(2)), 17 in World Health Organization
      obese class I (BMI, 30-34.9 kg/m(2)), 15 in class II (BMI, 35-39.9 kg/m(2)), and
      31 in class III (BMI >= 40 kg/m(2)), including 15 with BMI >= 45 kg/m(2). Image
      quality was scored as poor (1), moderate (2), good (3), or excellent (4).
      Patients with BMI >= 45 kg/m(2) and nondiagnostic image quality (<=2) were
      rescanned after repositioning to better center the heart in the field of view.
      Receiver-operating-curve analysis was applied to determine the BMI cutoff
      required to obtain diagnostic image quality (>=3). RESULTS: Receiver-operating
      curve analysis resulted in a cutoff BMI of 39 kg/m(2) (P < 0.001) for diagnostic
      image quality. In patients with BMI >= 40 kg/m(2), image quality was
      nondiagnostic in 81%; after CT-based attenuation correction this decreased to
      55%. Repositioning further improved image quality. Rescanning on a conventional
      SPECT camera resulted in diagnostic image quality in all patients with BMI >= 45
      kg/m(2). CONCLUSION: Patients with BMI >= 40 kg/m(2) should be scheduled for
      myocardial perfusion imaging on a conventional SPECT camera, as it is difficult
      to obtain diagnostic image quality on a cadmium-zinc-telluride camera.

PMID- 22870824
TI  - 18F-FDG uptake by metastatic axillary lymph nodes on pretreatment PET/CT as a
      prognostic factor for recurrence in patients with invasive ductal breast cancer.
AB  - This study assessed the maximum standardized uptake value of metastatic axillary
      lymph nodes in patients with invasive ductal breast cancer (IDC) to determine the
      pretreatment prognostic value of (18)F-FDG PET/CT for disease-free survival
      (DFS). METHODS: Sixty-five female IDC patients who had undergone pretreatment
      (18)F-FDG PET/CT and had pathologically confirmed axillary lymph node involvement
      without distant metastasis were enrolled. All patients showed complete remission
      after first-line treatment. To obtain nodal SUVmax, a transaxial image
      representing the highest (18)F-FDG uptake was carefully selected and a region of
      interest was manually drawn on the (18)F-FDG-accumulating lesion.
      Clinicopathologic parameters such as age, TNM stage, estrogen receptor status,
      progesterone receptor status, human epidermal growth factor receptor 2 status,
      and primary-tumor and nodal SUVmax on PET were analyzed for their usefulness in
      predicting recurrence. Combinatorial effects and interactions between variables
      that were significant by univariate analysis were examined using multivariate Cox
      proportional-hazards models. RESULTS: Twelve of 65 patients (18.5%) experienced
      recurrence during follow-up (median follow-up, 36 mo; range, 21-57 mo). Nodal
      SUVmax was significantly higher in patients with recurrence than in those who
      were disease-free (recurrence group: 5.2 +/- 2.3, vs. disease-free group: 1.9 +/-
      1.9, P < 0.0001). A receiver-operating-characteristic curve demonstrated a nodal
      SUVmax of 2.8 (sensitivity, 91.7%; specificity, 86.8%; area under the curve,
      0.890) to be the optimal cutoff for predicting DFS. Univariate analysis revealed
      that T stage, N stage, estrogen receptor status, and primary-tumor and nodal
      SUVmax correlated significantly with DFS. Among these 5 variables, only nodal
      SUVmax was found to be a single determinant of DFS by multivariate analysis
      (hazard ratio, 31.54; 95% confidence interval, 2.66-373.39; P = 0.0065).
      CONCLUSION: Nodal SUVmax on pretreatment (18)F-FDG PET/CT may be an independent
      prognostic factor for disease recurrence in patients with IDC.

PMID- 22870825
TI  - Brief owner absence does not induce negative judgement bias in pet dogs.
AB  - Humans in a negative emotional state are more likely to judge ambiguous stimuli
      as negative. In recent years, similar judgement biases have been found in some
      non-human animals that were exposed to long-term or short-term treatments aimed
      at influencing their affective states. Here we tested pet dogs in the presence
      and absence of their owners in a judgement bias test with an established go/no-go
      procedure. Even though owner absence is thought to induce a state of anxiety in
      dogs that have formed an attachment bond with their primary caretakers, we found
      no difference between the dogs' responses to ambiguous stimuli in the presence or
      absence of their owners. This result may be explained by the absence of anxiety
      in dogs that are accustomed to brief periods of separation from their owners, or
      by a sensitivity limit of the customary judgement bias tests in non-human animals
      when only a moderate, short-term state of anxiety is induced. In addition, we
      found significant differences between individuals and populations in the
      responses to ambiguous stimuli, which give impetus for further research.

PMID- 22870826
TI  - Vulnerability and the psychosocial aspects of tooth loss in old age: a Southern
      Brazilian study.
AB  - Extensive tooth loss and edentulism can have a negative impact on the general
      health and quality of life of older adults. The extent to which psychological and
      social factors affect an individual's decision to undergo tooth extraction and
      mouth clearance (extraction of all teeth), and the theoretical relationships
      between social structure, social life and oral health can be unraveled through
      qualitative research. This study aimed to explore the social and psychological
      factors involved in tooth extraction and mouth clearance within a historical
      perspective among rural Southern Brazilian older adults. It is based on
      qualitative data gathered via a series of eight focus groups among 41 older
      adults. Underlying the focus group discussions of different levels of health
      risks and resources for prevention of disease was the concept of vulnerability.
      Participants' responses illustrated that tooth loss and mouth clearance were
      related to a lack of public dental health policies and programs, were influenced
      by social norms (including values pertaining to gender), and were associated with
      a low level of oral health knowledge. The social and program-dependent contexts
      of vulnerability were shown to have played a major role in the development of
      norms and values towards tooth extraction and mouth clearance. Vulnerability must
      be reduced in order to prevent disease particularly among rural populations. The
      influence of fatalistic beliefs about the inevitable loss of teeth with age may
      negatively influence the acceptance of dental treatment and predilection for oral
      health self-care.

PMID- 22870827
TI  - Differential topochemistry of three cationic amino acid transporter proteins,
      hCAT1, hCAT2 and hCAT3, in the adult human brain.
AB  - The cellular uptake of L-arginine and other cationic amino acids (such as L
      lysine and L-ornithine) is mainly mediated by cationic amino acid transporter
      (CAT) proteins. Despite the important roles of cationic amino acid transporters
      for normal brain functioning and various brain diseases there is currently only
      fragmentary knowledge about their cellular and regional distribution patterns in
      the human brain. We mapped the immunohistochemical localization of human cationic
      amino acid transporters 1, 2 and 3 (hCAT1, 2, and 3) throughout five adult human
      brains and found a wide but uneven distribution of these transporters. All three
      hCAT1s were mainly localized in neurons, but were also found in numerous
      astrocytes, oligodendrocytes, plexus choroideus epithelial cells, and small blood
      vessels. The highest density of hCAT expressing neurons was observed in the
      hypothalamus, in some areas of the cerebral cortex, the thalamic reticular
      nucleus and the caudate nucleus, whereas weak to moderate expression was detected
      in the hippocampus, the prefrontal cortex (hCAT1 only), pons, brain stem and
      cerebellum. In contrast to what has been found in rodent brain, we detected hCAT2
      and hCAT3 also in astrocytes. Overall, each hCAT has its characteristic,
      individual cerebral expression patterns, which, however, overlap with the others.

PMID- 22870828
TI  - [Surgical treatment of particularly complicated forms of gall-bladder and
      anhepatic bile-duct diseases].
AB  - The authors offer analysis of surgical treatment methods of patients suffering
      from complicated forms of gall-bladder and anhepatic bile-excreting ducts'
      diseases. In elaborating tactics for treatment of the above-mentioned pathology
      the presently existing technical and tactical approaches are considered and the
      most acceptable for receiving favourable results are chosen. In implementing the
      operation the authors gave utmost attention to the choice of the method of bile
      duct drainage depending on the severity of the disease, the age and the
      concomitant diseases.  Taking into consideration application of the most approved
      and effective methods of treatment of complicated forms of gall-bladder and bile
      duct diseases, 191 patients were operated within the period of 1990-2008 years.
      The operation cholecystectomy together with drainage of the choledochus was
      carried out in 64 cases, choledochoduodenostomy - in 54 cases,
      choledochojejunostomy - in 59 cases, reconstruction of the choledochus over a T
      tube Kerr's drainage - in 8 cases. The portion of the gall-duct retained after
      the first operation was removed to 3 patients. There were 18 (9,4%) cases of
      complications in post-operation period, 8 patients died, lethality was 4,2%.

PMID- 22870829
TI  - Frequencies of erythrocyte blood groups alleles and haplotyphes in women with
      benign tumors of the uterus.
AB  - The erythrocyte blood groups antigens are associated with risk of certain
      malignancies though the correlation between blood groups and diseases is still
      unclear. The investigation is aimed at determining the correlation between benign
      tumors of the uterus and erythrocyte blood groups alleles and haplotyphes in
      patients of Adjara Oncology Centre.  Blood of 60 women with benign tumors of the
      uterus and of 60 healthy women of reproductive age were investigated for ABO and
      Rh system alleles and haplotypes. Immunoserological methods have been used to
      identify the antigens. The obtained results were statistically processed. The ABO
      system gene alleles' frequency was computed by the formula proposed by F.
      Bernstein and used in investigation of three-allele genetic systems. The
      frequency of Rh-system genes, Rh-haplotypes is computed by the formula proposed
      by A. E. Mourant.   According to ABO systems in women with benign tumors of the
      uterus high frequencies of p (0,12) and q (0,21) alleles are found. When studying
      individual alleles of the Rh system in women with benign tumors, high frequency
      of D was noticed (0.8). In women with benign tumor of the uterus RhD allele
      frequency is statistically different to healthy women.    ABO systems gene
      alleles' significantly differ in healthy and diseased women. In women with benign
      tumor of the uterus only three Rh-system haplotypes have been found:  CDe, cDe,
      cde haplotypes.

PMID- 22870830
TI  - Differentiation between benign and malignant meningiomas using diffusion and
      perfusion MR imaging.
AB  - The purpose of the study was to investigate the utility of diffusion-weighted
      (DW) and perfusion-weighted (PW) MR imaging to differentiate benign and malignant
      meningiomas which were verified histologically. A total of 29 patients with
      meningiomas (22 benign and 7 malignant) underwent conventional, perfusion and
      diffusion MR imaging. Conventional MRI revealed the ordinary signs of tumor. The
      absolute apparent diffusion coefficient (ADC) and normalized ADC (NADC) ratio,
      maximal relative cerebral blood volume (rCBV) and the corresponding relative mean
      time to enhance (rMTE) in both tumour parenchyma and peritumoral edema were
      measured. The mean ADC of malignant meningiomas (0.64+/-0.12 x 10(-3) mm(2)/s)
      was significantly lower compared with benign meningiomas (0.89+/-0.09 x 10(-3)
      mm(2)/s; P<.0001). Mean NADC ratio in the malignant group (0.93+/-0.18) was also
      significantly lower than in the benign group (1.29+/-0.12; P<.0001). The mean
      maximal rCBV values of benign and malignant meningiomas were 7.18+/-4.12 and
      6.01+/-3.89, in the tumour parenchyma, and 1,07+/-0,95 and 3,85+/-1,41 in the
      peritumoral edema. The mean rMTE values were 1.14+/-0.23 and 1.24+/-0.27, in the
      tumour, and 0.88+/-0.24 and 1.21+/-0.31, in the peritumoral edema. The
      differences in rCBV and rMTE values between benign and malignant meningiomas were
      not significant (P>0.05) in the tumour parenchyma, but both were significant
      (p<0.05) in the peritumoral edema. Diffusion and perfusion MR imaging are useful
      in the preoperative differentiation between benign and malignant meningiomas.

PMID- 22870831
TI  - Delayed spleen rupture after blunt abdominal trauma (case report).
AB  - The aim of the article was to present and discuss the phenomenon of delayed fatal
      spleen rupture case. A 13-year-old boy was referred to hospital because of his
      poor general condition, convulsions, tachypnea, shallow breathing, severe
      paleness, abdominal tenderness, decrease in blood pressure, low blood hemoglobin
      levels, leukocytosis. Abdominal pain complaints began second day night, after
      abdominal trauma during soccer game with classmates. Autopsy macroscopic
      examination revealed coagulated blood in abdominal cavity and large perisplenic
      haematama. Spleen with a big subcapsular and intrasplenic hematoma was observed
      on dissection. It is concluded that early diagnosis is the most important measure
      to reduce mortality. In terms of autopsy examination, proper investigation during
      forensic autopsy will contribute in understanding the pathophysiology of this
      phenomenon.

PMID- 22870832
TI  - [The level of matrix metalloproteinases and type IV collagen in the gingival
      mucosa under different clinical forms of periodontitis in pre-and pubertal
      periods and their prognostic value].
AB  - The purpose of the study - the analysis of the prevalence and gravity of
      periodontal diseases among school adolescents and detection the relationship
      between the degree of periodontal tissues changes and the hormonal status of the
      prepubertal and pubertal periods.   The total number of observations - 618
      Tbilisi schoolchildren at the age of 9 to 17 years. Cohort group (n=50) was
      divided by age: 1) 9-13 years (n=26), 2) 14-17 years (n=24).  The material for
      morphological and immunohistochemical study were the samples of periodontal
      tissues, received during the tooth extraction according the orthodontic
      testimony.  The samples of the gingival mucosa was stained by hematoxylin and
      eosin, in the same samples the Matrix Metalloproteinases expression and activity
      were determined by immunohistochemistry using a primary antibody MMP-1 and MMP-2
      ("Novocastra", UK). The results of immunohistochemical reactions were estimated
      in scores by semiquantitative method. For the detection of type IV collagen in
      basement membranes the samples were stained by the "Direct Red-80" ("Sigma").  It
      was found that the increase of Matrix Metalloproteinases expression and the type
      IV collagen degeneration in basement membrane depend on the age, particularly the
      expression of MMP-1 and MMP-2 in the period of 14-17 years (puberty) is upwards
      than in the group of 9-13 years.  Studies have also demonstrated the clinical
      significance of Matrix Metalloproteinases MMR-1, 2 activity indicating the
      dissociation of the extracellular substance and type IV collagen in the
      assessment of severity and prognosis of periodontal complex pathology in pre-and
      pubertal periods.

PMID- 22870833
TI  - [Correlation between the ecological risk factors and significant index of caries
      in young children].
AB  - The influence of eco-pathogenic factors on mineralization of teeth hard tissues
      at early age was studied in 525 young children, 3 to 4 of ages. Tooth caries
      index was detected according to the indexes provided by WHO (World Health
      Organization): prevalence, intensity (dmf) and Significant Index of Caries (SIC).
      The studies revealed that the average rate of dental caries for studied group
      living in regions with ecologically favorable conditions is relatively lower than
      in ones living in regions with unfavorable conditions and equals to 39.6% and
      63.6%, respectively.   Comparative analysis of average and significant indexes 
      of dental caries showed that the difference is minimal in children population
      living in favorable conditions (1: 1.7) in comparison with the children living in
      ecologically contaminated regions, where the significant index exceeds the
      average one approximately three times as much.   According to the obtained
      results, it should be concluded that the dynamics of dental caries is mostly
      expressed in young children living in regions where air-pollution (with
      chemically aggressive substances) index several times exceeds the maximum
      allowable coefficient. Consequently, development and implementation of the
      special programs for caries-prevention in children population with low rate of
      caries-resistance, living in the above-mentioned conditions is of great
      importance.

PMID- 22870834
TI  - Cytomegalovirus bearing in children with sensorineural hearing losses.
AB  - The rate of bearing of cytomegalovirus, CMV, has been estimated in children
      suffering from inborn or newborn types of a sensorineural hearing loss of hard-to
      severe degrees. The test group comprised 15 hearing-loss children of 3-6 years of
      age. The control group included accidentally selected 30 healthy children of the
      same age without any hearing complains. In both groups the CMV-specific IgG
      antibodies were determined in blood via the enzyme-linked immunosorbent assay,
      ELISA. The excessive amount of IgG antibodies was found in 14 out of 15 children
      with sensorineural hearing losses being estimated objectively, via computer
      registration of auditory brainstem responses, ABRs, and in 14 out of 30 children
      with normal hearing, being also inspected objectively, via specialized screening
      procedure. The intergroup difference in CMV bearing rates, 93.3% and 46.7%,
      respectively, has been confirmed to be statistically significant (p=0.007). CMV
      bearing happens thus twice as much in sensorineural hearing-loss than in normally
      hearing children. Early detection of a hearing loss and early assessment of CMV
      bearing seem essential for an immediate start and, consequently, for a batter
      chance of positive outcomes of specific treatment-rehabilitation means.

PMID- 22870835
TI  - Influence of ferrotherapy on psychomotor development of children of yearly age
      with iron deficiency anemia.
AB  - According to universally acknowledged biopsychosocial model of development,
      numerous biological and environmental factors influence development of children.
      One of them is iron deficiency in the organism. The study assessed physical,
      motor and psychosocial development of children who at an early age had the
      diagnosis of iron deficiency anemia and had been treated by iron drugs. Their
      neurological, receptive, expressive and cognitive functions were assessed using
      BINS (Bayley's Infant's Neurodevelopmental Screen). The sample was divided into 2
      age groups: 16-20 and 21-24 months.   The study shows that in children, who had
      iron deficiency at an early age and had taken treatment with relevant drugs in a
      timely manner, the aggregate indicators of four clusters do not differ
      significantly from standard indicators submitted by BINS. We deem important time
      diagnosis of iron deficiency and beginning of respective treatment, in order to
      avoid problems in psychomotor development; Timely treatment will favor the
      processes of development of child's social and school preparedness.

PMID- 22870836
TI  - [Epidemiological characteristics and pathogenetical peculiaritries of subclinical
      infections caused with hepatitis B and C viruses among pregnant women living in
      Baku].
AB  - The aim of the work was to conduct serological tests of blood serums of 1782
      pregnant women living in Baku for spread of hepatitis B and C viral infections.
      Results obtained demonstrated that frequency of serologic markers detection among
      pregnant women had no substantial difference from analogous parameters in healthy
      donors living in Baku.   Biochemical tests of blood serums contained HBsAg or/and
      anti-HCV. Both hepatotropis viral infections in pregnant women were not
      accompanied with biochemical signs of liver dysfunction in the blood.

PMID- 22870837
TI  - [The role of aldosterone and IL-6 in the pathogenesis of inflammation in familial
      Mediterranean fever].
AB  - The aim of the article was to study the role of aldosterone and IL-6 - in the
      pathogenesis of familial Mediterranean fever (FMF). The hypersecretion  of  IL-6
      and "the syndrome of aldosterone excess" in patients with  FMF was revealed. The
      hyperactivity of the inflammatory process in FMF is one of the phenotypic factors
      of defective gene expression in FMF.   In the course of the development of
      familial Mediterranean fever in presence of amyloidosis, the inhibition of
      mineralocorticoid function, and constantly elevated IL-6 levels, which gradually
      progresses bringing to an exhaustion of that function and to the dissociation of
      the adaptative-regulatory homeostasis.  The given introduction enlarges view
      points of pathogenesis of FMF and confirms the multifactorial nature of FMF, in
      the development of which besides the genetic factors, has a great role of
      phenotypic factors, as well. From the phenotypic factors is hyperaldosteronemia,
      hyperinterleukinemia-6, which reacts with defective gene and promotes its
      expression, and brings to the development of FMF attacks.

PMID- 22870838
TI  - Bilateral long styloid process detected at autopsy (case report).
AB  - The aim of the article was to reveal the significance of prolonged styloid
      process detected at forensic autopsy.  A-61-year-old man was found dead in his
      home. The crime scene investigation exposed suicide by hanging. On internal
      autopsy examination pulmonary edema and congestion of all internal organs were
      identified. Dissection of the neck structures revealed 90 mm in length on the
      right side, 70 mm in length on the left side, bilateral long styloid process.
      Distal parts of the prolonged styloid process were situated between external and
      internal carotid artery. Our aim was to discuss the significance of prolonged
      styloid process detected at forensic autopsy.

PMID- 22870839
TI  - Tobacco smoking attributable mortality and years of potential life lost in
      Georgia.
AB  - Smoking-attributable deaths and years of potential life lost were estimated using
      the formula adopted to estimate UK and US deaths caused by smoking. These
      estimates are based on sex-specific proportions by age of current and ex-smokers
      and rates of relative risk. For prevalence data we used data of 2010 STEPS survey
      in Georgia and Georgia Reproductive Health Survey 2005. Relative risks for
      potentially fatal diseases due to smoking are those that were used to estimate UK
      1995 deaths. They were derived from years 1984-1988 of the Cancer Prevention
      Study II (CPS II). Smoking attributable mortality was estimated for year 2008,
      period when registration of deaths was done by adopted methods and institutions.
      By the calculations according to mortality data of year 2008 number of active
      smoking attributable deaths were 4331. Smoking is related with 10,1% of all
      deaths. By causes of death smoking attributed is 30% of all deaths caused by
      cancers, 10% of cardiovascular diseases, 9% of respiratory and 7% of digestive
      diseases. About 72500 potential years of life is lost in Georgia during year 2008
      due to active smoking. Great majority of this burden is related with cardio
      vascular diseases and cancers.

PMID- 22870840
TI  - Study of implementation level of tobacco restriction policy in cafes and
      restaurants of Georgia.
AB  - Before year 2008 smoking was partially restricted in cafes and restaurants of
      Georgia. In 2009 Georgian Parliament adopted amendment in law "Concerning Tobacco
      Control" and strengthened partial restriction in cafes and restaurants, namely
      required that 50% of territory of those facilities must be smoke free.  To
      observe status of implementation of tobacco control legislation in field of
      prohibition/restriction of smoking in cafes and restaurants conducted observation
      of those facilities and in-depth interviews of their owners/staff.  Observation
      in cafes and restaurants were done in big regional centers of Georgia, namely in
      Tbilisi (Capital), Telavi, Kutaisi, Batumi, Rustavi, Gori, Akhaltsikhe and
      Zugdidi. At all 176 cafes/restaurants were observed (22,4% of all registered
      cafes/restaurants in Georgia). For qualitative part of the study 1-2 persons from
      staff of the cafe or restaurant or its owner available during the observation was
      interviewed.  Field work was done during 2011-2012. It must be mentioned that
      during this period was not observed any important change in legislation and/or
      enforcement of smoking ban/restrictions in those facilities.  Study instrument
      were guide for observer that contained two parts - observational and open-ended
      questions for owners and staff.  Observation of cafes/restaurants in Georgia
      shows that 89,8% of them violate existing restriction on smoking. All restaurants
      and 85% of cafes violate the law.  Only 18 (10,2%) cafes are in compliance with
      the legislation and all of them have total ban. Despite to the fact that more
      than 50% of observed cafes/restaurants were located in Tbilisi, absolute majority
      (88,1%) of smoke free facilities are in regions (mainly in Kutaisi, Zugdidi and
      Gori). Qualitative study of owners/staff of the facilities found factors that
      probably are influential in determination of smoking status of cafes/restaurants.
      Namely, decisions on those kinds of issues are made by owners according to
      business interest and private attitude. Because of absence of enforcement
      activities requirement of tobacco control legislation is not taken into
      consideration.  Existing partial restriction doesn't have support from great
      majority of cafes/restaurants, because it is difficult to implement. At the same
      time part of owners/staff don't support any type of ban or restriction, because
      of their fear to loose smoker clients. At that qualitative study and observation
      shows that this opinion is assumption and not on practice or evidence based
      argument.  Despite to this assumption, total ban on smoking in cafes and
      restaurants is understood as "coming legislation" and main requirement to this
      possible development is to provide "ban for all" and information of general
      public.

PMID- 22870841
TI  - Medical discourse in pathological anatomy.
AB  - The paper is devoted to the peculiarities of medical discourse in pathological
      anatomy as coherent speech and as a linguistic correlate of medical practice
      taking into account the analysis of its strategies and tactics. The purpose of
      the paper is to provide a multifaceted analysis of the speech strategies and
      tactics of pathological anatomy discourse and ways of their implementation. The
      main strategies of medical discourse in pathological anatomy are an anticipating
      strategy, a diagnosing strategy and an explaining one. The supporting strategies
      are pragmatic, conversational and a rhetorical one. The pragmatic strategy is
      implemented through contact establishing tactics, the conversational one - with
      the help of control tactics, the rhetorical one - with the help of attention
      correction tactics. The above mentioned tactics and strategies are used in the
      distinguishing of major, closely interrelated strategies: "the contact strategy"
      (to establish contact with a patient's relatives - phatic replicas of greeting
      and addressing) and "the strategy of explanation" (used in the practice of a
      pathologist for a detailed explanation of the reasons of a patient's death). The
      ethic aspect of speech conduct of a doctor-pathologist is analyzed.

PMID- 22870842
TI  - [Postnatal neurogenesis and regenerative capabilities of the central nervous
      system (review)].
AB  - Postnatal neurogenesis and regeneration opportunities of experimentally damaged
      areas of the cerebral cortex in various mammalian species were studied by the use
      of light and electron microscopy, autoradiography and transplantation. Back in
      the 70s of the 20th century by I. Mepisashvili and her school, it has been found
      that at the early stages of postnatal development of animals in the matrix area
      of the dorsolateral wall of the lateral ventricles there is a certain reserve of
      indifferent cells, which, like the embryonic period, by means of proliferation,
      migration and subsequent differentiation of their derivatives replenish the
      structure of the cortex with new glial and nerve cells and appear to be the major
      source of reparative regeneration of the CNS. The definite regularity in the rate
      of matrix cells implementation in the animals that occupy different levels of
      phylogenetic level (mouse, rat, rabbit, cat, dog) was established. It was found
      that in the immature-born animals (rabbit) the reserve of indifferent cells is
      maintained longer and their postnatal implementation takes place in a more
      extended period as compared to mature-born animals (guinea pig). The rates of the
      matrix cells implementation are in direct proportion to the functional load of
      the cerebral cortex. It has been demonstrated that these cells serve as the main
      source of regeneration of cortical lesions in the early postnatal period, while
      the defined biostimulants promote the intensification of this process. As a
      result of transplantation of the matrix of embryonic and early postembryonic
      cells in the experimentally damaged cortex of adult rats the quite successful
      restoration of the structure, characteristic of the relevant department of the
      cerebral cortex was observed.

PMID- 22870843
TI  - Different aspects of virus persistence (review).
AB  - The article reviews different aspects of virus persistence in human organism.
      Persistence is a capability acquired and strengthened in the process of evolution
      of many viruses that is the means of maintenance of species. Viruses of measles,
      poliomyelitis, mite-like encephalitis, B and C hepatitis, herpes, retro and HIV
      viruses persist in human organism.  Persistence is used by various viruses at
      various levels; they have different adaptive power and no different pathologic
      output. But in any case, the necessary condition is that virus should escape from
      elimination reactions of immune control system. At the same time, the important
      thing is not to save free virus but to save infected cell. While discussing long
      term viral persistence, it is impossible to mark off distinctly the importance of
      biological participation of macroorganism and provoker in this process. The
      output of the relationship with infect cell is conditioned on the one hand by
      permissiveness of cell system, on the other hand by strain pathogen city. The
      details of attenuation mechanisms of microorganism's different reactions in cases
      of illness with the same strain are not known well yet. Although, it is clear
      that in chronic persistence the leading role still has immune system disbalance.
      In disbalance genesis of immunological equilibration virus-induced changes of
      immunocompetent cells are high.

PMID- 22870844
TI  - Making the case for health literacy.

PMID- 22870845
TI  - An issue of blood: the healing of the woman with the haemorrhage (Mark 5.24B-34;
      Luke 8.42B-48; Matthew 9.19-22) in early medieval visual culture.
AB  - The textual and visual tradition of the story of the woman with the haemorrhage
      (Mark 5.24b-34parr), the so-called Haemorrhoissa, is related in a specific way to
      Christ's healing miracles but also to conceptions of female menstrual blood. We
      notice that with regard to the specific 'issue of blood' of the Haemorrhoissa,
      there is a visual lacuna in the specific iconography that developed around the
      story from early Christian times: in the transposition from text to image, there
      is no immediate depiction of her bleeding. However, the early medieval reception
      of the story also became an important catalyst for uterine taboos, menstruation
      and tits relation to magical healing, understood as a system of health practices.
      In this context, the dissemination of the motif in everyday material culture
      clearly points to a deep-rooted connection to uterine and menstrual issues. The
      paper considers both expressions and their-anthropologically framed-relation to
      this female 'issue of blood', which the Haemorrhoissa came to embody and
      epitomise literally, as well as figuratively.

PMID- 22870846
TI  - Pastor and lay leader perceptions of barriers and supports to HIV ministry
      maintenance in an African American church.
AB  - Clergy and lay leaders have a pivotal role in the development and maintenance of
      HIV Ministries within the African American church. However, little is known about
      the actual roles these men and women have, the barriers they face and the
      supports they have found in the development and maintenance of an HIV Ministry.
      The purpose of this study is to examine the role, barriers and supports clergy
      and lay leaders experienced in the development of a long-standing HIV ministry in
      an African American church. These data were gathered from a larger ethnographic
      study, which examined the role of religious culture in the development,
      implementation and maintenance of an HIV ministry. Data for this study were
      collected through in-depth semi-structured interviews. Results revealed that the
      primary role of clergy and lay leaders involved dispelling myths surrounding HIV
      and ensuring congregational support. The primary barrier to the development and
      maintenance was views regarding sexuality. The primary support was their
      relationships with congregants that lived with HIV and AIDS. This information can
      assist in developing interventions to enhance the African American church
      movement toward HIV ministries. 

PMID- 22870847
TI  - Physical barriers to carotenoid bioaccessibility. Ultrastructure survey of
      chromoplast and cell wall morphology in nine carotenoid-containing fruits and
      vegetables.
AB  - BACKGROUND: The ultrastructural characterisation of cellular components is a key
      element in revealing the bases for differences in nutrient bioaccessibility among
      fruits and vegetables and their derived products. Together, cell walls and
      chromoplasts constitute the two major physical barriers to carotenoid release
      from the food matrix (structure) during digestion. In general, larger cells with
      thinner cell walls are most likely to fail under mechanical pressure. In relation
      to chromoplasts, the substructures plastoglobuli, crystals and membranes give
      decreasing rates of carotenoid solubilisation when exposed to digestive forces.
      RESULTS: This paper describes cell wall and chromoplast structures in nine
      carotenoid-storing raw fruits and vegetables. Watermelon and melon cells were
      shown to have the largest cells concomitant with thin, non-fibrous cell walls,
      while carrot, hypodermal grapefruit and sweet potato cells were smallest with
      fibrous or dense cell walls. Mango fruit showed the highest proportion of
      globules to other substructures. Carrot, papaya and tomato contained many
      crystalline structures. Finally, watermelon, mango and butternut squash developed
      a high proportion of membranous structures. CONCLUSION: A more precise
      description of the physical characteristics of foods that stand as barriers to
      bioaccessibility can help in understanding which are more or less inhibitory for
      particular foods.

PMID- 22870848
TI  - Bifurcation analysis applied to a model of motion integration with a multistable
      stimulus.
AB  - A computational study into the motion perception dynamics of a multistable
      psychophysics stimulus is presented. A diagonally drifting grating viewed through
      a square aperture is perceived as moving in the actual grating direction or in
      line with the aperture edges (horizontally or vertically). The different percepts
      are the product of interplay between ambiguous contour cues and specific
      terminator cues. We present a dynamical model of motion integration that performs
      direction selection for such a stimulus and link the different percepts to
      coexisting steady states of the underlying equations. We apply the powerful tools
      of bifurcation analysis and numerical continuation to study changes to the
      model's solution structure under the variation of parameters. Indeed, we apply
      these tools in a systematic way, taking into account biological and mathematical
      constraints, in order to fix model parameters. A region of parameter space is
      identified for which the model reproduces the qualitative behaviour observed in
      experiments. The temporal dynamics of motion integration are studied within this
      region; specifically, the effect of varying the stimulus gain is studied, which
      allows for qualitative predictions to be made.

PMID- 22870849
TI  - Laser versus stapler: outcomes in endoscopic repair of Zenker diverticulum.
AB  - OBJECTIVES/HYPOTHESIS: To analyze a single surgeon's experience with endoscopic
      CO(2)  laser and stapler repair of Zenker diverticulum (ZD) by comparing
      dysphagia and regurgitation outcomes. STUDY DESIGN: Retrospective chart review of
      148 patient charts. METHODS: Medical records of all patients receiving endoscopic
      repair of ZD with either CO(2)  laser (61 patients) or stapler (67 patients) were
      reviewed. Additional data included demographics (age and sex), size (cm),
      preoperative and postoperative symptoms, need for revision, and complications.
      Symptoms of dysphagia were graded based on a modified Functional Oral Intake
      Scale 1 to 4 scale (1 = normal intake; 4 = severely limited/G-tube dependent).
      Regurgitation was also graded on a 1 to 4 scale (1 = no regurgitation; 4 =
      aspiration events). RESULTS: We noted no difference in patient age or defect size
      (laser, 3.26 cm; stapler, 3.53 cm; P .135). Significant differences were noted in
      return trips to the operating room for failed procedures (laser, 0; stapler, 7; P
      = .009), length of stay (laser, 3.19 days; stapler, 1.29 days; P < .001), time to
      oral intake (laser, 3.01 days; stapler, 1.22 days; P < .001). Significant
      improvement occurred in laser and staple patient symptom scales following surgery
      (P < .001). Laser dysphagia and regurgitation scores showed greater improvement
      when compared to stapler scores (P < .001). CONCLUSIONS: Endoscopic CO(2)  laser
      and staple methods are effective in treating ZD. The laser can have greater
      efficacy and result in lower recurrence rates. Both methods are analyzed and
      compared.

PMID- 22870850
TI  - Stereotactic radiosurgical treatment of brain metastasis of primary tumors that
      rarely metastasize to the central nervous system.
AB  - We evaluated the local control of gamma knife stereotactic radiosurgery (GKSRS)
      in the treatment of cerebral metastases from primary tumors that rarely
      metastasize to the central nervous system (CNS). There is little published data
      on this subject with very few series on specific primary tumors. We present our
      experience treating these lesions with GKSRS combined with a review of the
      salient literature. A retrospective study of 36 patients who collectively
      underwent 44 GKSRS procedures for CNS metastatic disease was undertaken. Our
      series includes four patients with sarcoma, two with prostate cancer, three with
      thyroid cancer, five with endometrial cancer, seven with ovarian cancer, two with
      cervical cancer, six with esophageal cancer, two with bladder cancer, one with
      liver cancer, one with pancreatic cancer, and three with testicular cancer. With
      44 gamma knife sessions treating 74 tumors, 63 tumors showed no radiographic
      evidence of progression, and 13 tumors demonstrated radiographic progression
      between one and 12 months after gamma knife treatment. In six patients in the
      population, further treatment with GKSRS was necessary due to enlargement of
      untreated lesions or new metastatic disease. GKSRS for uncommon CNS metastases is
      appears to be efficacious in controlling the treated tumor. The majority of
      tumors treated in our study did not progress post gamma knife.

PMID- 22870851
TI  - Hip fractures in Norway 1999-2008: time trends in total incidence and second hip
      fracture rates: a NOREPOS study.
AB  - Declining incidences of hip fractures are reported from western countries. Norway
      has among the highest rates in the world. The aim of this study was to
      investigate trends in total hip fracture rates in Norway between 1999 and 2008
      and risk of second hip fractures. All hospitalizations given a hip fracture
      diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10)
      (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved
      with accompanying surgical procedure codes and additional diagnoses. A total of
      93,123 hip fractures were identified between 1999 and 2008 in persons >=50 years.
      Annual incidences of hip fractures were calculated and tested for trends. Rates
      of first and second hip fractures (2006-2008) were compared. The age-standardized
      total incidence of hip fracture decreased by 13.4 % (95 % confidence interval
      (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted
      rates of second hip fractures did not change in the observation period. In those
      with a prior hip fracture, the age-standardized risk of a subsequent hip fracture
      was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in
      men. Total hip fracture rates declined in both genders during 1999-2008, whereas
      rates of second hip fractures did not change.

PMID- 22870852
TI  - Antibodies against human BLyS and APRIL attenuate EAE development in marmoset
      monkeys.
AB  - B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor)
      and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of
      the TNF superfamily with a central role in B cell survival. Antibodies against
      these factors have potential therapeutic relevance in autoimmune inflammatory
      disorders with a proven pathogenic contribution of B cells, such as multiple
      sclerosis (MS). In the current study we performed a multi-parameter efficacy
      comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a
      common marmoset (Callithrix jacchus) model of experimental autoimmune
      encephalomyelitis (EAE). A MS-like disease was induced by immunization with
      recombinant human myelin/oligodendrocyte glycoprotein (rhMOG) in complete
      Freund's adjuvant. The results show that the anti-BLyS and anti-APRIL antibody
      cause significant depletion of circulating CD20+ B cells, but a small subset of
      CD20 + CD40(high) B cells was not depleted. Induction of CD20+ B cell depletion
      from lymph nodes was only observed in the anti-BLyS treated monkeys. Both
      antibodies had a significant inhibitory effect on disease development, but all
      monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were
      sacrificed with the same clinical signs as saline-treated monkeys, but
      nevertheless displayed significantly reduced spinal cord demyelination. This
      effect was not observed in the anti-APRIL treated monkeys. The two antibodies had
      a different effect on T cell subset activation and the profiles of ex vivo
      released cytokines. In conclusion, treatment with anti-BLyS and anti-APRIL delays
      the development of neurological disease in a relevant preclinical model of MS.
      The two mAbs achieve this effect via different mechanisms.

PMID- 22870854
TI  - [Phototoxic drug reaction - the dark side of summer].

PMID- 22870853
TI  - Multimodal analysis in acute and chronic experimental autoimmune
      encephalomyelitis.
AB  - Different experimental autoimmune encephalomyelitis models (EAE) have been
      developed. However, due to the different experimental conditions applied,
      observations simultaneously considering different pathological targets are still
      scarce. Using EAE induced in Dark Agouti rats with syngenic whole spinal cord
      homogenate suspended in incomplete Freund's adjuvant, we here analyze
      neurosteroidogenic machinery, cytokine levels, microglial cells, infiltration of
      inflammatory cells, myelin proteins and Na(+), K(+)-ATPase pump activity in the
      spinal cord. Data obtained in the acute phase of the disease confirmed that
      neurological signs were accompanied by the presence of perivascular infiltrating
      T cells (CD3(+) cells) and activated monocytic/microglial cells (ED1(+) and MHC
      II(+)) in the spinal cord. In particular, the number of MHC-II(+) cells was
      significantly increased in association with increased expression of pro- (i.e.,
      TNF-alpha, IL-1beta) and anti-inflammatory (i.e., TGF-beta) cytokines as well as
      with decreased expression of proteolipid protein and myelin basic protein. During
      the chronic phase of the disease, the number of MHC-II(+) cells was still
      increased, although less than in the acute phase. Changes in the number of MHC
      II(+) cells were associated with decreased Na(+),K(+)-ATPase enzymatic activity.
      A general decrease in the levels of neuroactive steroids, with the exception of
      an increase in tetrahydroprogesterone and 17beta-estradiol, was detected in the
      acute phase. These changes were maintained or reverted in the chronic phase of
      EAE. In conclusion, we report that modifications in the neuroimmune response in
      the acute and chronic phases of EAE are associated with specific changes in
      myelin proteins, Na(+),K(+)-ATPase pump and in the levels of neuroactive
      steroids.

PMID- 22870855
TI  - Biochemical analysis of protein SUMOylation.
AB  - SUMOylation, the covalent attachment of Small Ubiquitin-like MOdifier (SUMO)
      polypeptides to other proteins, is among the most important post-translational
      modifications that regulate the functional properties of a large number of
      proteins. SUMOylation is broadly involved in cellular processes such as gene
      transcription, hormone response, signal transduction, DNA repair, and nuclear
      transport. SUMO modification has also been implicated in the pathogenesis of
      human diseases, such as cancer, neurodegenerative disorders, and viral infection.
      Attachment of a SUMO protein to another protein is carried out in multiple steps
      catalyzed by three enzymes. This unit describes and discusses the in vitro
      biochemical methods used for investigating each step of the SUMOylation process.
      In addition, a high-throughput screening protocol is included for the
      identification of inhibitors of SUMOylation.

PMID- 22870856
TI  - Assays for investigating deSUMOylation enzymes.
AB  - Post-translational modifications by the SUMO (Small Ubiquitin-like MOdifier)
      family of proteins are recently discovered essential regulatory mechanisms. All
      SUMO proteins are synthesized as larger precursors that are matured by SUMO
      specific proteases, known as SENPs, which remove several C-terminal amino acids
      of SUMO to expose the Gly-Gly motif. SENPs also remove SUMO modifications from
      target proteins, making this modification highly dynamic. At least six
      deSUMOylation enzymes, all of which are encoded by essential genes, have been
      identified in mammals. SENP1 has been shown to play an important role in the
      development of prostate cancer and in angiogenesis. This unit describes and
      discusses methods for characterizing the deSUMOylation enzymes. These assays
      enable the identification of inhibitors of these enzymes and investigation of
      their mechanism of inhibition in order to develop research tools and future
      therapeutics.

PMID- 22870857
TI  - Single nucleotide analysis of cytosine methylation by whole-genome shotgun
      bisulfite sequencing.
AB  - Unlike other methods to assess methylation, whole-genome shotgun bisulfite
      sequencing is used to generate quantitative genome-wide methylation profiles at
      single-nucleotide resolution. As described in this unit, this method allows for
      the quantitative measurement of methylation at each cytosine base by treatment of
      genomic DNA with sodium bisulfite followed by sequencing and alignment of the
      reads to a reference genome.

PMID- 22870858
TI  - Design and assembly of large synthetic DNA constructs.
AB  - The availability of custom synthetic gene-length DNA products removes numerous
      bottlenecks in research efforts, making gene synthesis an increasingly common
      commercial service. However, the assembly of synthetic oligonucleotides into
      large, custom DNA constructs is not especially difficult, and performing "in
      house" gene synthesis has time and cost advantages. This unit will treat both the
      concerns of design and physical assembly in gene synthesis, including how to
      design DNA sequences for synthesis and the design of overlapping oligonucleotide
      schemes to ensure facile assembly into the final product. Assembly is
      accomplished using a reliable series of PCR reactions, with a troubleshooting
      assembly protocol included, which not only assembles difficult sequences but
      allows identification of the source of a failure down to a pair of
      oligonucleotides.

PMID- 22870859
TI  - Enrichment of error-free synthetic DNA sequences by CEL I nuclease.
AB  - As the availability of DNA sequence information has grown, so has the need to
      replicate DNA sequences synthetically. Synthetically produced DNA sequences allow
      the researcher to exert greater control over model systems and allow for the
      combinatorial design and construction of novel metabolic and regulatory pathways,
      as well as optimized protein-coding sequences for biotechnological applications.
      This utility has made synthetically produced DNA a hallmark of the molecular
      biosciences and a mainstay of synthetic biology. However, synthetically produced
      DNA has a significant shortcoming in that it typically has an error rate that is
      orders of magnitude higher when compared to DNA sequences derived directly from a
      biological source. This relatively high error rate adds to the cost and labor
      necessary to obtain sequence-verified clones from synthetically produced DNA
      sequences. This unit describes a protocol to enrich error-free sequences from a
      population of error-rich DNA via treatment with CEL I (Surveyor) endonuclease.
      This method is a straightforward and quick way of reducing the error content of
      synthetic DNA pools and reliably reduces the error rates by >6-fold per round of
      treatment.

PMID- 22870860
TI  - Database of DNA polymerases.
AB  - The DNA Polymerase Database (Polbase) is intended to compile the wealth of
      existing DNA polymerase information from public and private records into an open,
      searchable database.

PMID- 22870861
TI  - Classical Galactosaemia in Ireland: incidence, complications and outcomes of
      treatment.
AB  - Newborn screening for the inborn error of metabolism, classical galactosaemia
      prevents life-threatening complications in the neonatal period. It does not
      however influence the development of long-term complications and the complex
      pathophysiology of this rare disease remains poorly understood. The objective of
      this study was to report the development of a healthcare database (using
      Distiller Version 2.1) to review the epidemiology of classical galactosaemia in
      Ireland since initiation of newborn screening in 1972 and the long-term clinical
      outcomes of all patients attending the National Centre for Inherited Metabolic
      Disorders (NCIMD). Since 1982, the average live birth incidence rate of classical
      galactosaemia in the total Irish population was approximately 1:16,476 births.
      This reflects a high incidence in the Irish 'Traveller' population, with an
      estimated birth incidence of 1:33,917 in the non-Traveller Irish population.
      Despite early initiation of treatment (dietary galactose restriction), the long
      term outcomes of classical galactosaemia in the Irish patient population are
      poor; 30.6 % of patients >= 6 yrs have IQs <70, 49.6 % of patients >= 2.5 yrs
      have speech or language impairments and 91.2 % of females >= 13 yrs suffer from
      hypergonadotrophic hypogonadism (HH) possibly leading to decreased fertility.
      These findings are consistent with the international experience. This emphasizes
      the requirement for continued clinical research in this complex disorder.

PMID- 22870862
TI  - Silencing IDO in dendritic cells: a novel approach to enhance cancer
      immunotherapy in a murine breast cancer model.
AB  - Cancer immunotherapeutic agents (vaccines) in the form of antigen-loaded
      dendritic cells (DCs) reached an important milestone with the recent approval of
      Provenge, the first DC vaccine for treatment of prostate cancer. Although this
      heralds a new era of tumor immunotherapy, it also highlights the compelling need
      to optimize such DC-based therapies as they are increasingly tested and used to
      treat human patients. In this study we sought to augment and enhance the
      antitumor activity of a DC-based vaccine using siRNA to silence expression of
      immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) in DCs. We report here
      that DCs loaded with tumor antigens, but with siRNA-silenced IDO expression, were
      introduced into 4T1 breast tumor-bearing mice, the treatment: (i) lengthened the
      time required for tumor onset, (ii) decreased tumor size compared to tumors grown
      for equal lengths of time in mice treated with antigen-loaded DCs without IDO
      silencing and (iii) reduced CD4(+) and CD8(+) T cell apoptosis. Furthermore,
      immunization with IDO-silenced DCs enhanced tumor antigen-specific T cell
      proliferation and CTL activity, and decreased numbers of CD4(+) CD25(+) Foxp3(+)
      T(reg). This study provides evidence to support silencing of immunosuppressive
      genes (IDO) as an effective strategy to enhance the efficacy of DC-based cancer
      immunotherapeutic.

PMID- 22870863
TI  - Spontaneous abscess of the anterior abdominal wall caused by Clostridium
      perfringens resistant to clindamycin.

PMID- 22870864
TI  - Energetics and structure of uranium(VI)-acetate complexes in dimethyl sulfoxide.
AB  - The thermodynamics of the complexation between uranium(VI) and acetate in
      dimethyl sulfoxide (DMSO) was studied at 298 K in an ionic medium of 0.1 mol dm(
      3) tetrabutyl ammonium perchlorate. The results show that the uranyl ion forms
      three strong successive mononuclear complexes with acetate. The complexes, both
      enthalpically and entropically stabilized, are significantly more stable in DMSO
      than in water. This feature can be ascribed to the weak solvation of acetate in
      DMSO. The thermodynamic parameters for the formation of the uranium(VI) complexes
      with acetate in DMSO are compared with those with ethylenediamine in the same
      solvent. The difference between the two ligand systems reveals that, for the
      complexation reactions involving charge neutralization, the reorganization of the
      solvent gives a very important contribution to the overall complexation
      energetics. The coordination mode of acetate in the uranyl complexes and the
      changes of the solvation sphere of UO(2)(2+) upon complexation were investigated
      by FT-IR spectroscopy in DMSO and in acetonitrile/DMSO mixtures. In addition, DFT
      calculations were performed to provide an accurate description of the
      complexation at the molecular level. The experimental and calculated results
      suggest that acetate is solely bidentate to UO(2)(2+) in the 1:1 and 1:3
      complexes but mono- and bidentate in the 1:2 complexes. The DFT calculations also
      indicate that the medium effects must always be taken into account in order to
      gain accurate information on the complex formation in solution. In fact, the
      relative stability of the reaction products changes markedly when the DFT
      calculations are carried out in vacuum or in DMSO solution.

PMID- 22870865
TI  - Essential oils from Schinus terebinthifolius leaves - chemical composition and in
      vitro cytotoxicity evaluation.
AB  - CONTEXT: In folk medicine, Schinus terebinthifolius Raddi (Anacardiaceae), has
      been used as a remedy for ulcers, respiratory problems, wounds, rheumatism, gout,
      diarrhea, skin ailments and arthritis, as well as to treat tumors and leprosy.
      OBJECTIVE: To investigate the chemical composition and cytotoxicity of essential
      oil from leaves of S. terebinthifolius as well as the identification of active
      compounds from this oil. MATERIAL AND METHODS: Essential oil from S.
      terebinthifolius leaves, obtained by hydrodistillation using a Clevenger-type
      apparatus, was characterized in terms of its chemical composition. Also, the
      crude oil was subjected to chromatographic separation procedures to afford an
      active fraction composed of alpha- and beta-pinenes. These compounds, including
      hydrogenation (pinane) and epoxydation (alpha-pinene oxide) derivatives from
      alpha-pinene, were tested in vitro against murine melanoma cell line (B16F10
      Nex2) and human melanoma (A2058), breast adenocarcinoma (MCF7), leukemia (human
      leukemia (HL-60) and cervical carcinoma (HeLa) cell lines. RESULTS: Forty-nine
      constituents were identified in the oil (97.9% of the total), with germacrene D
      (23.7%), bicyclogermacrene (15.0%), beta-pinene (9.1%) and beta-longipinene
      (8.1%) as the main compounds. The crude essential oil showed cytotoxic effects in
      several cell lines, mainly on leukemia and human cervical carcinoma. Fractions
      composed mainly of alpha- and beta-pinenes as well as those composed of
      individually pinenes showed effective activities against all tested cell lines.
      Aiming to determinate preliminary structure/activity relationships, alpha-pinene
      was subjected to epoxydation and hydrogenation procedures whose obtained alpha
      pinene oxide showed an expressive depression in its cytotoxicity effect, similar
      as observed to pinane derivative. DISCUSSION AND CONCLUSION: The obtained results
      indicated that the monoterpenes alpha- and beta-pinenes could be responsible to
      the cytotoxic activity detected in the crude oil from leaves of S.
      terebinthifolius. In addition, it was possibly inferred that the presence of
      double bond in their structures, mainly at endocyclic position, is crucial to
      cytotoxic potential detected in these derivatives.

PMID- 22870866
TI  - Ignorance and utilization: mental health care outside the purview of the Indian
      state.
AB  - The paper discusses different positions by psychiatrists and anthropologists
      taken towards 'folk' mental health care and summarizes what has been said in
      favour of the folk sector. Further, examples indicating a changing relationship
      between the Indian state and the folk sector are outlined, including the impacts
      of the fire tragedy at the dargah of Erwadi in 2001. On this basis it is argued
      that a prevailing ignorance of the folk sector has provided it with some
      autonomy, while at the same time, recent attempts at collaboration tend to
      utilize folk practitioners rather than valuing their positive elements in their
      own right.

PMID- 22870867
TI  - Decarbonylative C-H coupling of azoles and aryl esters: unprecedented nickel
      catalysis and application to the synthesis of muscoride A.
AB  - A nickel-catalyzed decarbonylative C-H biaryl coupling of azoles and aryl esters
      is described. The newly developed catalytic system does not require the use of
      expensive metal catalysts or silver- or copper-based stoichiometric oxidants. We
      have successfully applied this new C-H arylation reaction to a convergent formal
      synthesis of muscoride A.

PMID- 22870868
TI  - Mouse precision-cut liver slices as an ex vivo model to study idiosyncratic drug
      induced liver injury.
AB  - Idiosyncratic drug-induced liver injury (IDILI) has been the top reason for
      withdrawing drugs from the market or for black box warnings. IDILI may arise from
      the interaction of a drug's reactive metabolite with a mild inflammation that
      renders the liver more sensitive to injury resulting in increased toxicity
      (inflammatory stress hypothesis). Aiming to develop a robust ex vivo screening
      method to study inflammatory stress-related IDILI mechanisms and to find
      biomarkers that can detect or predict IDILI, mouse precision-cut liver slices
      (mPCLS) were coincubated for 24 h with IDILI-related drugs and
      lipopolysaccharide. Lipopolysaccharide exacerbated ketoconazole (15 MUM) and
      clozapine (45 MUM) toxicity but not their non-IDILI-related comparators,
      voriconazole (1500 MUM) and olanzapine (45 MUM). However, the other IDILI-related
      drugs tested [diclofenac (200 MUM), carbamazepine (400 MUM), and troglitazone (30
      MUM)] did not cause synergistic toxicity with lipopolysaccharide after 24 h of
      incubation. Lipopolysaccharide further decreased the reduced glutathione levels
      caused by ketoconazole or clozapine in mPCLS after 24 h of incubation, which was
      not the case for the other drugs. Lipopolysaccharide significantly increased
      nitric oxide (NO), cytokine, and chemokine release into the mPCLS media, while
      the treatment with the drugs alone did not cause any substantial change. All
      seven drugs drastically reduced lipopolysaccharide-induced NO production.
      Interestingly, only ketoconazole and clozapine increased the lipopolysaccharide
      induced granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) release. Pilot experiments showed that
      diclofenac and troglitazone, but not carbamazepine, demonstrated synergistic
      toxicity with lipopolysaccharide after a longer incubation of 48 h in mPCLS. In
      conclusion, we have developed an ex vivo model to detect inflammatory stress
      related liver toxicity and identified ketoconazole, clozapine, troglitazone, and
      diclofenac as drugs that showed synergistic toxicity with lipopolysaccharide.
      Reduced glutathione, G-CSF, and GM-CSF were identified to be potential biomarkers
      for IDILI-inducing drugs mediated by inflammatory stress, and mPCLS appear to be
      a promising screening tool to further unravel the mechanism of IDILI.

PMID- 22870869
TI  - Antioxidants for the treatment of patients with severe angioproliferative
      pulmonary hypertension?
AB  - SIGNIFICANCE: Pathobiological mechanisms that contribute to pulmonary
      vasoconstriction, lung vascular remodeling, and the development of right heart
      failure include the generation of reactive oxygen and nitrogen species and the
      response of lung vascular and cardiac cells to these molecules. We review the
      information regarding oxidant stress balanced by antioxidant mechanisms and the
      role of oxidants and antioxidants in hypoxic pulmonary hypertension and their
      potential role in an animal model of severe pulmonary arterial hypertension
      (PAH). RECENT ADVANCES: In human lung tissue from patients with idiopathic PAH,
      we find reduced superoxide dismutase activity and high expression of the oxidant
      stress markers nitrotyrosine and 8-OH-guanosine. In the Sugen 5416/chronic
      hypoxia model of PAH, lung tissue expression of nitrotyrosine and hemeoxygenase 1
      (HO-1) is substantial, while HO-1 expression in the failing right ventricle is
      decreased. This model, based on administration of the VEGF receptor blocker Sugen
      5416 and chronic hypoxia (Su/Hx), reproduces many of the characteristic features
      of severe angioobliterative human PAH. Treatment of Su/Hx rats with protandim,
      which nuclear factor erythroid-2 related factor (Nrf2)-dependently upregulates
      the expression of genes encoding antioxidant enzymes, protects against right
      heart failure without affecting angioobliterative PAH. CRITICAL ISSUES: In human
      severe PAH, patient survival is determined by the function of the stressed right
      ventricle; investigation of oxidative and nitrosative stresses and their
      potential contribution to right heart failure is necessary. FUTURE DIRECTIONS:
      Antioxidant therapeutic strategies may be of benefit in the setting of human
      severe PAH. Whether antioxidant strategies affect lung vascular remodeling and/or
      prevent right heart failure remains to be examined.

PMID- 22870870
TI  - Analysis of association between the MUC4 g.8227C>G polymorphism and production
      traits in Italian heavy pigs using a selective genotyping approach.
AB  - In pigs, susceptibility to enterotoxigenic Escherichia coli (ETEC) K88 strains
      (locus F4bcR) is determined by a dominant allele, with the recessive allele
      determining resistance. The susceptible allele also appeared to be associated
      with higher growth rate even with discordant results. A single nucleotide
      polymorphism (SNP) in exon 7 of the mucin 4 (MUC4) gene (DQ848681:g.8227C>G),
      shown to be in close linkage disequilibrium with the F4bcR locus, has been used
      as marker to identify susceptible pigs, substituting invasive villous adhesion
      tests. We herein analyzed this SNP in Italian local breeds and applied a
      selective genotyping approach in Italian Large White, Italian Landrace, and
      Italian Duroc comparing allele frequency distribution in groups of pigs with
      extreme estimated breeding values (EBV) for average daily gain (ADG) and backfat
      thickness (BFT) to evaluate if this marker is associated with these traits.
      Allele G (associated with susceptibility to ETEC) was associated with higher ADG
      and BFT in Italian Large White (P=6.66E-04 and P=0.012, respectively) and higher
      ADG in Italian Landrace (P=7.23E-12). This polymorphism was poorly informative in
      Italian Duroc. Antagonistic associations of the MUC4 g.8227C>G alleles on
      susceptibility to ETEC and growth performances evidence the complexity of
      applying marker assisted selection in pig breeding.

PMID- 22870871
TI  - Screening of a xylanase clone from a fosmid library of rumen microbiota in Hu
      sheep.
AB  - The glycosyl hydrolase family 11, which is responsible for carbohydrate
      metabolism, was identified in the open reading frame (ORF) 6 of a xylanase
      positive clone from a fosmid library of rumen microbiota of Hu sheep. A BLASTP
      search of GenBank revealed that ORF6 encoded a 355-amino acid putative
      endoxylanase, having 61% similarity (e(-73)) to endo-1,4-beta-xylanase of
      Fibrobacter succinogenes S85 (YP_003250510.1). Predicted with the SWISS-MODEL,
      there were two separate beta-sandwich clusters linked with a high serine
      containing linker in ORF6. The N-terminal beta-sandwich is a novel endoxylanase
      of the glycosyl hydrolase family 11 with a specific activity of 1150.00 U/mg. The
      optimal pH and temperature for this enzyme were shown to be pH 5.0 and 50 degrees
      C, respectively. The C-terminal helped increase the stability of the xylanase but
      decreased the activity to some degree. The C-terminal beta-sandwich could bind
      avicel, but no conserved domain could be found. It may be a novel carbohydrate
      binding module.

PMID- 22870872
TI  - Evaluation of interferon response induced by anti-myostatin shRNA constructs in
      goat (Capra hircus) fetal fibroblasts by quantitative real time-polymerase chain
      reaction.
AB  - RNAi is an evolutionary conserved, highly efficient, and cost effective technique
      of gene silencing. It holds considerable promise and success has been achieved
      both in vitro and in vivo experiments. However, it is not devoid of undesirable
      side effects as dsRNA can trigger the immune response and can also cause non
      specific off-target gene silencing. In the present study, silencing of myostatin
      gene, a negative regulator of myogenesis, was evaluated in caprine fetal
      fibroblasts using three different shRNA constructs. Out of these three
      constructs, two constructs sh1 and sh2 showed, 72% and 50% reduction (p<0.05) of
      myostatin mRNA, respectively. Efficient suppression (42-86%) of MSTN gene
      (p<0.05) was achieved even by reducing the concentration of shRNA constructs. The
      induction of classical interferon stimulated gene (Oligoandenylate Synthetase-1,
      OAS-1) was studied to analyze the immune response against shRNAs. Notably, a
      reduction in the potency of shRNAs to induce interferon response was observed at
      lower concentration for OAS1 gene. The results obtained in the study would be
      helpful in the abrogation of the bystander effects of RNAi for long term stable
      expression of anti-MSTN expression constructs in the muscle.

PMID- 22870873
TI  - Polymorphisms of the myostatin gene and its relationship with reproduction traits
      in the Bian chicken.
AB  - Myostatin, or growth and differentiation factor 8, is a member of the
      transforming growth factor-beta superfamily; it functions as a negative regulator
      of skeletal muscle development and growth in mammals. In this study, single
      nucleotide polymorphisms in the 5' regulatory region and exon 1 of the myostatin
      gene were detected by PCR-SSCP in the Bian, Jinghai, Youxi, and Arbor Acre
      chickens, and the associations of the polymorphisms with reproduction traits were
      analyzed. Seven SNPs (A326G, C334G, C1346T, G1375A, A1473G, G1491A, and G2283A)
      were found in the myostatin gene. Association analysis showed that the G2283A
      were significantly associated with reproduction traits. Bian chickens of the GG
      genotype had a greater age at first egg than those of the GA and AA genotypes
      (P<0.01). Correspondingly, Bian chickens of the GA and AA genotypes had larger
      egg number at 300 days than those of the GG genotype (P<0.05 and P<0.01,
      respectively). Bian chickens of the AA genotype had significantly higher body
      weight at 300 days than those of the GG genotype (P<0.05). These results
      suggested that the myostatin gene may have certain effects on reproduction traits
      other than merely as a negative regulator of skeletal muscle development and
      growth in mammals previously reported.

PMID- 22870874
TI  - Detection of polymorphism and sequence characterization of Toll-like receptor 7
      gene of Indian goat revealing close relationship between ruminant species.
AB  - In this study, approximately 3.4 kb nucleotide sequence of caprine TLR7 (Toll
      like receptor 7) gene was generated from twelve different Indian goat breeds
      belonging to different geographical regions. Goat TLR7 gene ORF (Open Reading
      Frame) was found to be 3141 nucleotides long coding for 1046 amino acids similar
      to sheep. The sequence analysis at nucleotide level revealed goat TLR7 having
      99.5% homology with sheep, followed by other livestock species. Simple Modular
      Architecture Research Tool (SMART) was used for the structural analysis of goat
      TLR7 that showed the presence of 22 leucine rich repeats (LRRs) along with single
      Toll/interleukin-1 receptor (TIR) domains. TIR domain, when compared, was found
      to be similar in ruminant species, goat, sheep, cattle, and buffalo. The
      phylogenetic analysis also revealed grouping of all ruminant species together,
      goat being closer to sheep followed by cattle and buffalo. A total of 22
      polymorphic sites were observed in TLR7 gene of 24 goats representing 12
      different breeds, out of which 19 were present within the coding region and three
      in 3'UTR. Out of the seven nonsynonymous SNPs, two were in ectodomains and one in
      TIR domain. Overall our results indicate substantial variation within goat TLR7
      gene, which could be exploited for association with disease susceptibility.

PMID- 22870875
TI  - Polymorphisms of mitochondrial ATPase 8/6 genes and association with milk
      production traits in Holstein cows.
AB  - The maternal effect has been widely proposed to affect the production traits in
      domestic animals. However, the sequence polymorphisms of mitochondrial DNA
      (mtDNA) and association with milk production traits in Holstein cows have
      remained unclear. In this study, we investigated the single nucleotide
      polymorphisms (SNPs) of mtDNA ATPase 8/6 genes and association with four milk
      production traits of interest in 303 Holstein cows. A total of 18 SNPs were
      detected among the 842 bp fragment of ATPase 8/6 genes, which determined six
      haplotypes of B. taurus (H1-H4) and B. indicus (H5-H6). The mixed model analysis
      revealed that there was significant association between haplotype and 305-day
      milk yield (MY). The highest MY was observed in haplotype H4. However, we did not
      detect statistically significant differences among haplotypes for the traits of
      milk fat (MF), milk protein (MP), and somatic cell count (SC). The overall
      haplotype diversity and nucleotide diversity of ATPase 8/6 genes were 0.563 +/-
      0.030 and 0.00609 +/- 0.00043, respectively. The results suggested that
      mitochondrial ATPase 8/6 genes could be potentially used as molecular marker to
      genetically improve milk production in Holstein cows.

PMID- 22870876
TI  - Species identification of ten common farm animals based on mitochondrial 12S rRNA
      gene polymorphisms.
AB  - Bio-techniques such as genetic manipulation, marker-assisted selection, and
      identity test have largely facilitated the modern animal production practices. In
      the present study, we established a reliable and cost-effective molecular method
      of species identification for common farm animals. We first (re-)analyzed 179
      mitochondrial 12S rRNA gene sequences of ten farm animal species to determine the
      intra-species and species-specific variations. The PCR-RFLP method was
      subsequently designed to identify these species by using endonucleases BshNI,
      ScaI, AluI, and BfaI. The poultry and livestock species were first discriminated
      by one double-digestion of both BshNI and ScaI, which generated different
      fragment patterns (325 bp and 115 bp for poultry vs. 364 bp and 76 bp for
      livestock). The ten species could be further discerned according to species
      specific restriction pattern by subjecting to digestion of AluI and BfaI,
      respectively. Our approach would be more reliable by taking the intra-species
      variations into consideration and could be applied to species identity test,
      commercial fraud, and wildlife crime.

PMID- 22870877
TI  - The impact of ABCG2 on bovine mammary epithelial cell proliferation.
AB  - The ATP-binding cassette transporter, ABCG2, has been identified as a gene of
      significance in the regulation of bovine lactation by a number of gene mapping
      studies yet its role in lactational physiology remains unclear. We have used the
      potent ABCG2 specific inhibitor, Ko143, to investigate role of ABCG2 in primary
      bovine mammary epithelial cell (BMEC) proliferation and differentiation. After
      incubation with Ko143, the proliferation rate of BMECs was reduced at 48 and 72
      hours by up to 80% (P < 0.001), and the effect was dose-dependent (approximately
      40% with 10 nM Ko143 and 80% with 20 nM Ko143). Morphological changes in BMEC
      mammosphere formation were not observed when co-incubated with Ko143. Our results
      suggested that ABCG2 plays a role in mammary epithelial cell proliferation and
      that functional polymorphisms in this gene may influence the cellular compartment
      of the mammary gland and potentially milk production.

PMID- 22870878
TI  - Synthesis, reactivity, and resolution of a C2-symmetric, P-stereogenic
      benzodiphosphetane, a building block for chiral bis(phosphines).
AB  - Although the pyramidal inversion barriers in diphosphines (R(2)P-PR(2)) are
      similar to those in phosphines (PR(3)), P-stereogenic chiral diphosphines have
      rarely been exploited as building blocks in asymmetric synthesis. The synthesis,
      reactivity, and resolution of the benzodiphosphetane trans-1,2-(P(t
      Bu))(2)C(6)H(4) are reported. Alkylation with MeOTf followed by addition of a
      nucleophile gave the useful C(2)-symmetric P-stereogenic ligand BenzP* and novel
      analogues.

PMID- 22870879
TI  - The development of quality indicators in mental healthcare: a discrete choice
      experiment.
AB  - BACKGROUND: Health care regulatory agencies perform audits or inspections to
      judge the quality and safety of health care. This judgment is based on the
      assessment of a large set of health care indicators as accepted by the
      profession. However, there is a lack of knowledge about the influence of these
      indicators and whether a smaller number would be sufficient for a quality
      assessment or audit procedure. METHODS: A discrete choice experiment (DCE) was
      performed for the assessment of quality of care regarding the management of
      patients with schizophrenia and drug dependency in psychiatric institutes. Based
      on multidisciplinary guidelines for the treatment of schizophrenia and a visit of
      (co)inspectors of the Dutch Healthcare Inspectorate at all 33 integrated mental
      hospitals a set of 51 indicators were assessed in a subsequent interview. With
      the analysis of the results, 6 attributes were selected for the DCE as quality
      indicators. RESULTS: Seventy-six percent of all health services (co)inspectors (n
      = 33) involved in the inspection of mental health services, participated in the
      experiment. Respondents considered an operational elaborate treatment plan the
      most important indicator for the assessment of quality of care in a psychiatric
      institute, followed by a general care program, treatment outcome measurement, and
      involvement in treatment of patients and relatives. Pharmacotherapy and
      governance responsibility were valued as less important indicators. CONCLUSIONS:
      The results of this DCE show that there is a prioritisation in the six selected
      quality indicators. This might help health services (co) inspectors to enhance
      the efficiency and transparency of the quality of care assessment for patients
      with schizophrenia and/or drug dependency in psychiatric institutes.

PMID- 22870880
TI  - Gastric obstruction secondary to metastatic breast cancer: a case report and
      literature review.
AB  - INTRODUCTION: Gastrointestinal tract soft tissues metastasis is a well-known
      occurrence with invasive lobular breast cancer subtypes. Gastric involvement is
      more common, with reports of both diffuse and localized involvements. Usually, a
      gastric localized involvement presents as wall thickening with an appearance
      similar to that of a gastrointestinal stromal tumour; rarely does a localized
      metastatic deposit grow aggressively to present as a large tumour causing
      obstructive symptoms. Our case highlights one such unusual presentation in a
      patient presenting with non-specific gastrointestinal symptoms. To the best of
      our knowledge, there have been no previous reports on a similar presentation
      occurring from a localized metastasis. CASE PRESENTATION: A 65-year-old Caucasian
      woman awaiting an outpatient oral gastroduodenoscopy for symptoms of intermittent
      vomiting, epigastric pains and weight loss of six weeks' duration presented
      acutely with symptoms of haematemesis and abdominal distension. An initial
      contrast-enhanced computed tomography scan showed a grossly dilated stomach with
      a locally advanced stenosing tumour mass at the pylorus. Our patient had a
      history of left mastectomy and axillary clearance followed by adjuvant endocrine
      therapy for an oestrogen receptor- and progesterone receptor-positive, grade 2,
      invasive lobular breast cancer. The oral gastroduodenoscopy confirmed the
      computed tomography findings; biopsies of the pyloric mass on
      immunohistochemistry stains were strongly positive for pancytokeratin and gross
      cystic disease fluid proteins, consistent with an invasive lobular breast cancer
      metastasis. She received a palliative gastrojejunal bypass and her adjuvant
      endocrine treatment was switched over to exemestane. CONCLUSION: Our case
      highlights the aggressive behaviour of a localized gastric metastasis that is
      unusual and unexpected. Gastrointestinal symptomatology can be non-specific and,
      at times, non-diagnostic on conventional mucosal biopsies. A high index of
      clinical suspicion in patients with a previous history of invasive lobular breast
      cancer can aid in an early diagnosis and treatment. A combined treatment approach
      with chemoendocrine therapies achieves remission and improves patient survival.

PMID- 22870881
TI  - Isotope dilution-GC-MS/MS analysis of 16 polycyclic aromatic hydrocarbons in
      selected medicinal herbs used as health food additives.
AB  - Medicinal herbs have a very important role in health protection and disease
      control, and have been used in health foods. Polycyclic aromatic hydrocarbons
      (PAHs) have carcinogenic, biological and mutagenic effects. In this paper, the
      content of 16 PAHs as representative contaminants in nine Chinese medicinal
      herbs, as additives for health foods, was investigated in order to ensure food
      safety from this source. A highly sensitive isotope dilution-gas chromatography
      tandem mass spectrometry (ID-GC-MS/MS) method combined with gel permeation
      chromatography (GPC) and solid-phase extraction (SPE) was developed. Calibration
      curves showed good linearity for all PAHs (R2 > 0.999), and the limit of
      quantification (LOQ) ranged from 0.42 to 2.7 ug kg-1. Average recoveries for
      these compounds were in the range of 52.5-117%, 52.6-119% and 81.4-108% at the
      concentrations of 10, 50 and 250 ug kg-1 with RSD of 1.8-15%, 0.9-15% and 1.0
      15%, respectively. The proposed method was used for the analysis of nine Chinese
      medicinal herbs. Total levels of PAHs varied from 98.2 ug kg-1 (cassia seed) to
      2245 ug kg-1 (eucommia bark). The highest level was found for phenanthrene (Phe)
      in liquorice root (631.3 ug kg-1), indigowoad leaf (551.0 ug kg-1), rose flower
      (435.2 ug kg-1) and eucommia bark (432.3 ug kg-1). The proposed method could
      provide a useful basis for safety monitoring of herbs and risk management for
      PAHs in the health food industry.

PMID- 22870883
TI  - Anaesthesia in a patient with subarachanoidal haemorrhage and high oxygen
      affinity haemoglobinopathy (HB york): case report.
AB  - BACKGROUND: Approximately 90 haemoglobinopathies have been identified that result
      in abnormally high oxygen affinity. One of these is haemoglobinopathy York (HbY),
      first described in 1976. HbY causes an extreme leftward shift of the oxygen
      dissociation curve with the P50 value changing to 12.5 - 15.5 mmHg (normal value
      26.7 mmHg), indicating that approximately half of the haemoglobin is not
      available as oxygen carrier. Patients with haemoglobinopathies with increased
      oxygen affinity could suffer from the risk developing ischaemic complications due
      to a lack of functional oxygen carriers. This is, to best of our knowledge, the
      first case report on a patient with HbY published in connection with anesthesia.
      CASE PRESENTATION: A 42-year-old female with a severe headache and Glasgow coma
      scale (GCS) of 15 was admitted to the neurosurgical intensive care unit with a
      ruptured, right sided ICA aneurysm with consecutive subarachnoid haemorrhage
      [Fisher III, World Federation of Neurosurgical Societies (WFNS) I)]. The medical
      history of the patient included an erythrocytosis (Hb 17.5 g/dl) on the base of a
      high-oxygen-affinity haemoglobinopathy, called Hb York (HbY). With no time
      available to take special preoperative precautions, rapid blood loss occurred
      during the first attempt to clip the aneurysm. General transfusion procedures,
      according to the guidelines based on haemoglobin and haematocrit values, could
      not be applied due to the uncertainty in the oxygen carrier reduction. To
      maintain tissue oxygen supply, clinical indicators of ischaemia were instead
      utilized to gauge the appropriate required blood products, crystalloids and
      colloids replacements. Despite this, the patient survived the neurosurgical
      intervention without any neurological deficit. CONCLUSIONS: Family members of
      patients with HbY (and other haemoglobinopathies with increased oxygen affinity)
      should undergo clinical assessment, particularly if they are polycythaemic. If
      the diagnosis of HbY is confirmed, they should carry an "emergency
      anaesthesiology card" in order to avert perioperative risks arising from their
      "hidden" anemia.

PMID- 22870882
TI  - The relationship between body system-based chronic conditions and dental
      utilization for Medicaid-enrolled children: a retrospective cohort study.
AB  - BACKGROUND: Dental care is the most common unmet health care need for children
      with chronic conditions. However, anecdotal evidence suggests that not all
      children with chronic conditions encounter difficulties accessing dental care.
      The goals of this study are to evaluate dental care use for Medicaid-enrolled
      children with chronic conditions and to identify the subgroups of children with
      chronic conditions that are the least likely to use dental care services.
      METHODS: This study focused on children with chronic conditions ages 3-14
      enrolled in the Iowa Medicaid Program in 2005 and 2006. The independent variables
      were whether a child had each of the following 10 body system-based chronic
      conditions (no/yes): hematologic; cardiovascular; craniofacial; diabetes;
      endocrine; digestive; ear/nose/throat; respiratory; catastrophic neurological; or
      musculoskeletal. The primary outcome measure was use of any dental care in 2006.
      Secondary outcomes, also measured in 2006, were use of diagnostic dental care,
      preventive dental care, routine restorative dental care, and complex restorative
      dental care. We used Poisson regression models to estimate the relative risk (RR)
      associated with each of the five outcome measures across the 10 chronic
      conditions. RESULTS: Across the 10 chronic condition subgroups, unadjusted dental
      utilization rates ranged from 44.3% (children with catastrophic neurological
      conditions) to 60.2% (children with musculoskeletal conditions). After adjusting
      for model covariates, children with catastrophic neurological conditions were
      significantly less likely to use most types of dental care (RR: 0.48 to 0.73).
      When there were differences, children with endocrine or craniofacial conditions
      were less likely to use dental care whereas children with hematologic or
      digestive conditions were more likely to use dental care. Children with
      respiratory, musculoskeletal, or ear/nose/throat conditions were more likely to
      use most types of dental care compared to other children with chronic conditions
      but without these specific conditions (RR: 1.03 to 1.13; 1.0 to 1.08; 1.02 to
      1.12; respectively). There was no difference in use across all types of dental
      care for children with diabetes or cardiovascular conditions compared to other
      children with chronic conditions who did not have these particular conditions.
      CONCLUSIONS: Dental utilization is not homogeneous across chronic condition
      subgroups. Nearly 42% of children in our study did not use any dental care in
      2006. These findings support the development of multilevel clinical interventions
      that target subgroups of Medicaid-enrolled children with chronic conditions that
      are most likely to have problems accessing dental care.

PMID- 22870884
TI  - Anti-inflammatory property of Kalpaamruthaa on myocardium in type 2 diabetes
      mellitus induced cardiovascular complication.
AB  - Efficacy of Kalpaamruthaa (KA) on the modulation of inflammatory markers in
      cardiovascular disease (CVD) induced by type 2 diabetes mellitus in experimental
      rats has been investigated in this study. Oxidative stress in hyperglycemia
      develops CVD by increasing the inflammatory markers. Administration of KA reduced
      the blood glucose level towards baseline in rats with diabetes induced CVD.
      Plasma C-reactive protein was elevated in CVD, while its level was markedly
      reduced upon KA treatment. Inducible nitric oxide synthase and cycloxygenase-2
      expressions in immunoblots, interleukin-1beta and interleukin-6 expressions in
      reverse transcriptase polymerase chain reaction and immunohistochemical
      expressions of tumor necrosis factor-alpha and nuclear factor-kappaB were
      increased in CVD-induced rats. KA renders its protection by decreasing these
      inflammatory markers in CVD-induced rats. Histochemical analysis of mast cell was
      studied. KA treated rats showed reduced count of mast cell in CVD-induced rat
      myocardium. This study provides the evidence of cardiovascular protective effect
      of KA in type 2 diabetes mellitus through its anti-inflammatory property.

PMID- 22870886
TI  - Supporting the early use of echocardiography in blunt chest trauma.
AB  - This case reports a very unusual mechanism of cardiac rupture following an
      episode of multiple blunt chest trauma. The patient, a professional jockey, was
      trampled by horses, and although shocked on hospital admission, he did not
      present with signs and symptoms that were consistent with cardiogenic shock. This
      case highlights the difficult and subjective nature of clinical examination in
      emergency situations when dealing with cases of acute cardiac tamponade. It
      further emphasises the lack of sensitivity of traditional trauma imaging and
      investigative approaches such as the standard anteroposterior chest X-ray and
      electrocardiogram. The diagnosis of acute cardiac tamponade was not made until
      tertiary-care-centre arrival, when ultrasound technology in the form of bedside
      echocardiography was used, facilitating emergency surgery to repair a ruptured
      left ventricle. It is hoped that the sharing of this case will alert fellow
      clinicians to this uncommon but possible mechanism of cardiac rupture and
      subsequent tamponade, encourage the early use of echocardiography at the bedside
      in hypotensive blunt chest trauma cases and reinforce the principles of the
      Advanced Trauma Life Support course in treating trauma victims.

PMID- 22870885
TI  - Aggregation pathways of the amyloid beta(1-42) peptide depend on its colloidal
      stability and ordered beta-sheet stacking.
AB  - Amyloid beta (Abeta) fibrils are present as a major component in senile plaques,
      the hallmark of Alzheimer's disease (AD). Diffuse plaques (nonfibrous, loosely
      packed Abeta aggregates) containing amorphous Abeta aggregates are also formed in
      brain. This work examines the influence of Cu(2+) complexation by Abeta on the
      aggregation process in the context of charge and structural variations. Changes
      in the surface charges of Abeta molecules due to Cu(2+) binding, measured with a
      zeta-potential measurement device, were correlated with the aggregate
      morphologies examined by atomic force microscopy. As a result of the charge
      variation, the "colloid-like" stability of the aggregation intermediates, which
      is essential to the fibrillation process, is affected. Consequently, Cu(2+)
      enhances the amorphous aggregate formation. By monitoring variations in the
      secondary structures with circular dichroism spectroscopy, a direct
      transformation from the unstructured conformation to the beta-sheet structure was
      observed for all types of aggregates observed (oligomers, fibrils, and/or
      amorphous aggregates). Compared to the Abeta aggregation pathway in the absence
      of Cu(2+) and taking other factors affecting Abeta aggregation (i.e., pH and
      temperature) into account, our investigation indicates that formations of
      amorphous and fibrous aggregates diverge from the same beta-sheet-containing
      partially folded intermediate. This study suggests that the hydrophilic domain of
      Abeta also plays a role in the Abeta aggregation process. A kinetic model was
      proposed to account for the effects of the Cu(2+) binding on these two
      aggregation pathways in terms of charge and structural variations.

PMID- 22870887
TI  - Calpain-1 knockout reveals broad effects on erythrocyte deformability and
      physiology.
AB  - Pharmacological inhibitors of cysteine proteases have provided useful insights
      into the regulation of calpain activity in erythrocytes. However, the precise
      biological function of calpain activity in erythrocytes remains poorly
      understood. Erythrocytes express calpain-1, an isoform regulated by calpastatin,
      the endogenous inhibitor of calpains. In the present study, we investigated the
      function of calpain-1 in mature erythrocytes using our calpain-1-null [KO
      (knockout)] mouse model. The calpain-1 gene deletion results in improved
      erythrocyte deformability without any measurable effect on erythrocyte lifespan
      in vivo. The calcium-induced sphero-echinocyte shape transition is compromised in
      the KO erythrocytes. Erythrocyte membrane proteins ankyrin, band 3, protein 4.1R,
      adducin and dematin are degraded in the calcium-loaded normal erythrocytes but
      not in the KO erythrocytes. In contrast, the integrity of spectrin and its state
      of phosphorylation are not affected in the calcium-loaded erythrocytes of either
      genotype. To assess the functional consequences of attenuated cytoskeletal
      remodelling in the KO erythrocytes, the activity of major membrane transporters
      was measured. The activity of the K+-Cl- co-transporter and the Gardos channel
      was significantly reduced in the KO erythrocytes. Similarly, the basal activity
      of the calcium pump was reduced in the absence of calmodulin in the KO
      erythrocyte membrane. Interestingly, the calmodulin-stimulated calcium pump
      activity was significantly elevated in the KO erythrocytes, implying a wider
      range of pump regulation by calcium and calmodulin. Taken together, and with the
      atomic force microscopy of the skeletal network, the results of the present study
      provide the first evidence for the physiological function of calpain-1 in
      erythrocytes with therapeutic implications for calcium imbalance pathologies such
      as sickle cell disease.

PMID- 22870889
TI  - A fast and precise method to identify indolic glucosinolates and camalexin in
      plants by combining mass spectrometric and biological information.
AB  - In this manuscript, a fast and accurate identification and quantitation by mass
      spectrometry of indolic glucosinolates and camalexin involved in defense in
      Arabidopsis thaliana are described. Two elicitation systems, inoculation with
      Botrytis cinerea and treatment with AgNO(3), were used in Col-0 wild-type and
      mutant genotypes impaired in the biosynthesis of the selected metabolites.
      Identification of analytes was carried out by nontargeted LC/ESI-QTOF-MS
      profiling. Confirmation of indolic glucosinolates and camalexin was achieved by
      their absence in the cyp79B2/B3 and pad3 mutants as well as their respective
      fragmentation upon collision-induced dissociation. Camalexin accumulation was
      induced only after AgNO(3) treatment, whereas all indolic glucosinolates were
      constitutively present. Inoculation with Botrytis did not influence camalexin
      concentration but caused most aliphatic and indolic glucosinolates contents to
      decrease. Only the pen 3.1 mutant showed increased indolic glucosinolate levels
      after Botrytis or AgNO(3) treatments. In addition, profiles of secondary
      metabolite in nontreated Col-0 and mutant plants were analyzed by means of
      partial least squares coupled to discriminant analysis (PLS-DA), and differences
      in the basal levels of indolic glucosinolates and tryptophan between cyp79B2/B3
      plants and the rest of genotypes, including Col-0, were found. This probably has
      to be taken into consideration when comparing stress responses of Col-0 and
      cyp79B2/B3. The use of mutants carrying alterations in biosynthetic pathways is
      proposed as a useful strategy to identify secondary metabolites.

PMID- 22870888
TI  - Clinical features of human salmonellosis caused by bovine-associated subtypes in
      New York.
AB  - The objective of this study was to identify patient symptoms and case outcomes
      that were more likely to occur as a result of Salmonella infections caused by
      bovine-associated subtypes (isolates that matched contemporary bovine isolates
      from New York by serovar and pulsed-field gel electrophoresis pattern), as
      compared to salmonellosis caused by non-bovine-associated subtypes. Data were
      collected in 34 counties of New York that comprise the Foodborne Diseases Active
      Surveillance Network (FoodNet) catchment area of the Centers for Disease Control
      and Prevention Emerging Infections Program. Patients with specimen collection
      dates between March 1, 2008 and March 1, 2010 were included. Symptoms and
      outcomes of 40 cases infected with bovine-associated Salmonella subtypes were
      compared to those of 379 control-cases infected with Salmonella isolates that
      were not bovine-associated. Cases were significantly more likely to have invasive
      salmonellosis (odds ratio, 3.8; p-value=0.02), after adjusting for age group,
      gender, and race. In addition, there was a marginal association between case
      status and the presence of blood in the stool (p-value=0.1) while ill. These
      findings might have implications for patient management, as a history of
      consuming undercooked foods of bovine origin or having direct contact with cattle
      in the few days prior to illness could be useful for suggesting a more proactive
      diagnostic approach as well as close monitoring for the need to implement more
      aggressive therapy.

PMID- 22870890
TI  - Abatacept  in the treatment of lupus.
AB  - INTRODUCTION: In contrast to other areas in rheumatology, the therapeutic
      armamentarium in systemic lupus erythematosus (SLE) has lagged behind due to a
      number of reasons. While SLE is the prototypical multi-system autoimmune disease,
      its low incidence and the heterogeneity in its clinical manifestations have made
      it difficult to study. Despite advances in the understanding and application of
      immunology, the emergence of new targets has not been successfully validated
      largely due to the difficult-to-use outcome measures. Among the many targets
      studied, co-stimulation blockade that prevents activation of T cells by antigen
      presenting cells, poses an interesting concept that is plausible based on basic
      science, animal and early human studies. AREAS COVERED: The authors hereby review
      the development of abatacept in the treatment of SLE and possible future
      directions. EXPERT OPINION: Despite failure to achieve primary efficacy end
      points, the studies of abatacept in lupus provided tantalising evidence that co
      stimulatory blockade is a feasible option worthy of further exploration.

PMID- 22870891
TI  - Brain leukocyte infiltration initiated by peripheral inflammation or experimental
      autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled
      compartments of the forebrain and midbrain.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) has been considered as a preferential
      pathway of circulation for immune cells during neuroimmune surveillance. In order
      to evaluate the involvement of CSF-filled spaces in the pathogenesis of
      experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis,
      we performed a time-course analysis of immune cell association with the CSF
      containing ventricles, velae, and cisterns in two active models of this disease.
      METHODS: Guinea-pig spinal cord homogenate-induced EAE in rat and myelin
      oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte
      distribution and phenotypes were investigated by immunohistochemistry in serial
      sections of brain areas of interest, as well as in CSF withdrawn from rat. Immune
      cells associated with the choroid plexuses were quantified. RESULTS: Freund's
      adjuvant-induced peripheral inflammation in the absence of brain antigen led to a
      subtle but definite increase in the number of myeloid cells in the
      extraventricular CSF spaces. In both rats and mice, EAE was characterized by a
      sustained and initial infiltration of lymphocytes and monocytes within
      forebrain/midbrain fluid-filled compartments such as the velum interpositum and
      ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated
      periventricular and pericisternal parenchymal areas, along perivascular spaces or
      following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from
      rats included lymphocytes and neutrophils. The distinctive pattern of cell
      distribution suggests that both the choroid plexus and the vessels lying in the
      velae and cisterns are gates for early leukocyte entry in the central nervous
      system. B-cell infiltration observed in the mouse model was restricted to CSF
      filled extraventricular compartments. CONCLUSION: These results identified
      distinctive velae and cisterns of the forebrain and midbrain as preferential
      sites of immune cell homing following peripheral and early central inflammation
      and point to a role of CSF in directing brain invasion by immune cells during
      EAE.

PMID- 22870892
TI  - Blood chemistry values for shovelnose and lake sturgeon.
AB  - Blood chemistry panels are commonly used for assessing the general health of
      vertebrate animals. Here, we present novel blood chemistry data for two North
      American sturgeon species, shovelnose sturgeon Scaphirhynchus platorynchus and
      lake sturgeon Acipenser fulvescens. Measurements were done using a portable
      chemistry analyzer (VetScan Analyzer; Abaxis). Among the plasma values measured
      (mean +/- SD for shovelnose and lake sturgeon, respectively) were total proteins
      (3.7 +/- 0.9 and 2.8 +/- 0.4 g/dL), albumin (2.0 +/- 0.5 and 1.1 +/- 0.2 g/dL),
      globulin (1.7 +/- 0.7 and 1.7 +/- 0.3 g/dL), glucose (107 +/- 46 and 62 +/- 9.7
      mg/dL), sodium (Na(+); 132 +/- 3.6 and 150 +/- 14 mEq/L), potassium (K(+); 3.5 +/
      0.2 and 2.8 +/- 1.7 mEq/L), phosphorus (10.4 +/- 1.9 and 11.6 +/- 3.6 mg/dL),
      and aspartate aminotransferase (AST; 676 +/- 433 and 634 +/- 234 IU/L). Higher
      values for total proteins, albumin, glucose, and Na(+) in shovelnose sturgeon
      than in lake sturgeon probably are the result of handling stress. In addition,
      the plasma of male shovelnose sturgeon had higher concentrations of AST, glucose,
      and globulin than did that of females, whereas the plasma of females had higher
      concentrations of albumin and K(+) than that of males. This study is the first to
      report blood chemistry data for shovelnose sturgeon. Robust blood chemistry
      databases can be used by aquaculturists and fish managers for monitoring sturgeon
      health.

PMID- 22870893
TI  - Spleen index and mannose-binding lectin levels in four channel catfish families
      exhibiting different susceptibilities to Flavobacterium columnare and
      Edwardsiella ictaluri.
AB  - Edwardsiella ictaluri and Flavobacterium columnare are two bacterial pathogens
      that affect channel catfish Ictalurus punctatus aquaculture. At the Catfish
      Genetics Research Unit (U.S. Department of Agriculture, Agricultural Research
      Service), some progress has been made in selectively breeding for resistance to
      E. ictaluri; however, the susceptibility of these families to F. columnare is not
      known. Our objectives were to obtain baseline information on the susceptibility
      of channel catfish families (maintained as part of the selective breeding
      program) to E. ictaluri and F. columnare and to determine whether the spleen
      index and plasma levels of mannose-binding lectin (MBL) are predictive indicators
      of susceptibility to these pathogens. Four channel catfish families were used:
      family A was randomly chosen from spawns of fish that were not selectively bred
      for resistance; families B, C, and D were obtained after selection for resistance
      to E. ictaluri. All four families were immersion challenged with both bacterial
      pathogens; the spleen index and plasma MBL levels of unchallenged fish from each
      family were determined. Mean cumulative percent mortality (CPM) after E. ictaluri
      challenge ranged from 4% to 33% among families. Families A and B were more
      susceptible to F. columnare (mean CPM of three independent challenges = 95% and
      93%) than families C and D (45% and 48%), demonstrating that there is genetic
      variation in resistance to F. columnare. Spleen index values and MBL levels were
      not significantly different, indicating that these metrics are not predictive
      indicators of F. columnare or E. ictaluri susceptibility in the four tested
      families. Interestingly, the two families that exhibited the highest CPM after F.
      columnare challenges had the lowest CPM after E. ictaluri challenge. Further
      research on larger numbers of families is needed to determine whether there is
      any genetic correlation between resistance to E. ictaluri and resistance to F.
      columnare.

PMID- 22870894
TI  - MK3 controls Polycomb target gene expression via negative feedback on ERK.
AB  - BACKGROUND: Gene-environment interactions are mediated by epigenetic mechanisms.
      Polycomb Group proteins constitute part of an epigenetic cellular transcriptional
      memory system that is subject to dynamic modulation during differentiation.
      Molecular insight in processes that control dynamic chromatin association and
      dissociation of Polycomb repressive complexes during and beyond development is
      limited. We recently showed that MK3 interacts with Polycomb repressive complex 1
      (PRC1). The functional relevance of this interaction, however, remained poorly
      understood. MK3 is activated downstream of mitogen- and stress-activated protein
      kinases (M/SAPKs), all of which fulfill crucial roles during development. We here
      use activation of the immediate-early response gene ATF3, a bona fide PRC1 target
      gene, as a model to study how MK3 and its effector kinases MAPK/ERK and SAPK/P38
      are involved in regulation of PRC1-dependent ATF3 transcription. RESULTS: Our
      current data show that mitogenic signaling through ERK, P38 and MK3 regulates
      ATF3 expression by PRC1/chromatin dissociation and epigenetic modulation.
      Mitogenic stimulation results in transient P38-dependent H3S28 phosphorylation
      and ERK-driven PRC1/chromatin dissociation at PRC1 targets. H3S28 phosphorylation
      by itself appears not sufficient to induce PRC1/chromatin dissociation, nor ATF3
      transcription, as inhibition of MEK/ERK signaling blocks BMI1/chromatin
      dissociation and ATF3 expression, despite induced H3S28 phosphorylation. In
      addition, we establish that concomitant loss of local H3K27me3 promoter marking
      is not required for ATF3 activation. We identify pERK as a novel signaling
      induced binding partner of PRC1, and provide evidence that MK3 controls ATF3
      expression in cultured cells via negative regulatory feedback on M/SAPKs.
      Dramatically increased ectopic wing vein formation in the absence of Drosophila
      MK in a Drosophila ERK gain-of-function wing vein patterning model, supports the
      existence of MK-mediated negative feedback regulation on pERK. CONCLUSION: We
      here identify and characterize important actors in a PRC1-dependent epigenetic
      signal/response mechanism, some of which appear to be nonspecific global
      responses, whereas others provide modular specificity. Our findings provide novel
      insight into a Polycomb-mediated epigenetic mechanism that dynamically controls
      gene transcription and support a direct link between PRC1 and cellular responses
      to changes in the microenvironment.

PMID- 22870895
TI  - A systematic review of methods to diagnose oral dryness and salivary gland
      function.
AB  - BACKGROUND: The most advocated clinical method for diagnosing salivary
      dysfunction is to quantitate unstimulated and stimulated whole saliva
      (sialometry). Since there is an expected and wide variation in salivary flow
      rates among individuals, the assessment of dysfunction can be difficult. The aim
      of this systematic review is to evaluate the quality of the evidence for the
      efficacy of diagnostic methods used to identify oral dryness. METHODS: A
      literature search, with specific indexing terms and a hand search, was conducted
      for publications that described a method to diagnose oral dryness. The electronic
      databases of PubMed, Cochrane Library, and Web of Science were used as data
      sources. Four reviewers selected publications on the basis of predetermined
      inclusion and exclusion criteria. Data were extracted from the selected
      publications using a protocol. Original studies were interpreted with the aid of
      Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. RESULTS: The
      database searches resulted in 224 titles and abstracts. Of these abstracts, 80
      publications were judged to meet the inclusion criteria and read in full. A total
      of 18 original studies were judged relevant and interpreted for this review. In
      all studies, the results of the test method were compared to those of a reference
      method.Based on the interpretation (with the aid of the QUADAS tool) it can be
      reported that the patient selection criteria were not clearly described and the
      test or reference methods were not described in sufficient detail for it to be
      reproduced. None of the included studies reported information on
      uninterpretable/intermediate results nor data on observer or instrument
      variation. Seven of the studies presented their results as a percentage of
      correct diagnoses. CONCLUSIONS: The evidence for the efficacy of clinical methods
      to assess oral dryness is sparse and it can be stated that improved standards for
      the reporting of diagnostic accuracy are needed in order to assure the
      methodological quality of studies. There is need for effective diagnostic
      criteria and functional tests in order to detect those individuals with oral
      dryness who may require oral treatment, such as alleviation of discomfort and/or
      prevention of diseases.

PMID- 22870896
TI  - Structural brain changes in First Episode Schizophrenia compared with Fronto
      Temporal Lobar Degeneration: a meta-analysis.
AB  - BACKGROUND: The authors sought to compare gray matter changes in First Episode
      Schizophrenia (FES) compared with Fronto-Temporal Lobar Degeneration (FTLD) using
      meta-analytic methods applied to neuro-imaging studies. METHODS: A systematic
      search was conducted for published, structural voxel-based morphometric MRI
      studies in patients with FES or FTLD. Data were combined using anatomical
      likelihood estimation (ALE) to determine the extent of gray matter decreases and
      analysed to ascertain the degree of overlap in the spatial distribution of brain
      changes in both diseases. RESULTS: Data were extracted from 18 FES studies
      (including a total of 555 patients and 621 comparison subjects) and 20 studies of
      FTLD or related disorders (including a total of 311 patients and 431 comparison
      subjects). The similarity in spatial overlap of brain changes in the two
      disorders was significant (p = 0.001). Gray matter deficits common to both
      disorders included bilateral caudate, left insula and bilateral uncus regions.
      CONCLUSIONS: There is a significant overlap in the distribution of structural
      brain changes in First Episode Schizophrenia and Fronto-Temporal Lobar
      Degeneration. This may reflect overlapping aetiologies, or a common vulnerability
      of these regions to the distinct aetio-pathological processes in the two
      disorders.

PMID- 22870897
TI  - Diagnosis of latent tuberculosis infection in healthy young adults in a country
      with high tuberculosis burden and BCG vaccination at birth.
AB  - BACKGROUND: One third of the world's population is thought to have latent
      tuberculosis infection (LTBI) with the potential for subsequent reactivation of
      disease. To better characterize this important population, studies comparing
      Tuberculin Skin Test (TST) and the new interferon-gamma release assays including
      QuantiFERON(r)-TB Gold In-Tube (QFT-GIT) have been conducted in different parts
      of the world, but most of these have been in countries with a low incidence of
      tuberculosis (TB). The aim of this study was therefore to evaluate the use of QFT
      GIT assay as compared with TST in the diagnosis of LTBI in Ethiopia, a country
      with a high burden of TB and routine BCG vaccination at birth. METHODS: Healthy
      medical and paramedical male students at the Faculty of Medicine, Addis Ababa
      University, Ethiopia were enrolled into the study from December 2008 to February
      2009. The TST and QFTG-IT assay were performed using standard methods. RESULTS:
      The mean age of the study participants was 20.9 years. From a total of 107 study
      participants, 46.7% (95%CI: 37.0% to 56.6%) had a positive TST result (TST>=10
      mm), 43.9% (95%CI: 34.3% to 53.9%) had a positive QFT-GIT assay result and 44.9%
      (95%CI: 35.2% to 54.8%) had BCG scar. There was strong agreement between TST (TST
      >=10mm) and QFT-GIT assay (Kappa = 0.83, p value = 0.000). CONCLUSION: The TST
      and QFT-GIT assay show similar efficacy for the diagnosis of LTBI in healthy
      young adults residing in Ethiopia, a country with high TB incidence.

PMID- 22870898
TI  - The effectiveness of nurse practitioners working at a GP cooperative: a study
      protocol.
AB  - BACKGROUND: In many countries out-of-hours care faces serious challenges,
      including shortage of general practitioners, a high workload, reduced motivation
      to work out of hours, and increased demand for out-of-hours care. One response to
      these challenges is the introduction of nurse practitioner as doctor substitutes,
      in order to maintain the (high) accessibility and safety of out of hours care.
      Although nurse practitioners have proven to provide equally safe and efficient
      care during daytime primary care, it is unclear whether substitution is effective
      and efficient in the more complex out of hours primary care. This study aims to
      assess the effects of substitution of care from general practitioners to nurse
      practitioners in an out of hours primary care setting. DESIGN: A quasi
      experimental study is undertaken at one "general practitioner cooperative" to
      offer out-of-hours care for 304.000 people in the South East of the Netherlands.
      In the experimental condition patient care is provided by a team of one nurse
      practitioner and four general practitioners; where the nurse practitioner
      replaces one general practitioner during one day of the weekend from 10 am to 5
      pm. In the control condition patient care is provided by a team of five general
      practitioners during the other day of the weekend, also from 10 am to 5 pm. The
      study period last 15 months, from April 2011 till July 2012. METHODS: Data will
      be collected on number of different outcomes using a range of methods. Our
      primary outcome is substitution of care. This is calculated using the number and
      characteristics of patients that have a consultation at the GP cooperative. We
      compare the number of patients seen by both professionals, type of complaints,
      resource utilization (e.g. prescription, tests, investigations, referrals) and
      waiting times in the experimental condition and control condition. This data is
      derived from patient electronic medical records. Secondary outcomes are: patient
      satisfaction; general practitioners workload; quality and safety of care and
      barriers and facilitators. DISCUSSION: The study will provide evidence whether
      substitution of care in out-of-hours setting is safe and efficient and give
      insight into barriers and facilitators related to the introduction of nurse
      practitioners in out-of-hours setting. TRIAL REGISTRATION: ClinicalTrials.gov ID
      NCT01388374.

PMID- 22870899
TI  - Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson's
      disease.
AB  - BACKGROUND: Alterations in blood-brain barrier permeability have been proposed to
      represent a relevant factor contributing to Parkinson's disease progression.
      However, few studies have addressed this issue in patients at different stages of
      disease. METHODS: Albumin was measured in cerebrospinal fluid and serum samples
      obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47
      age-matched control subjects. The albumin ratio (AR) was calculated to assess
      blood-cerebrospinal fluid and blood-brain barrier function. The group of patients
      with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1
      and 2 and 27, with a score ranging from 2.5 to 4. RESULTS: Statistically
      significant differences in albumin ratio were found between patients with
      advanced disease, and both early-stage and unaffected groups. Conversely, early
      phase patients did not differ from healthy subjects. Additionally, dopaminergic
      treatment seems to exert a possible effect on AR values. CONCLUSIONS: Our study
      demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier,
      blood-brain barrier, or both, characterize Parkinson's disease progression. The
      associations between clinical scores, treatments and biochemical findings suggest
      a progressive impairment of barrier integrity during the course of the disease.

PMID- 22870900
TI  - Diastolic dysfunction and mortality in early severe sepsis and septic shock: a
      prospective, observational echocardiography study.
AB  - BACKGROUND: Patients with severe sepsis or septic shock often exhibit
      significant cardiovascular dysfunction. We sought to determine whether severity
      of diastolic dysfunction assessed by transthoracic echocardiography (TTE)
      predicts 28-day mortality. METHODS: In this prospective, observational study
      conducted in two intensive care units at a tertiary care hospital, 78 patients
      (age 53.2 +/- 17.1 years; 51% females; mean APACHE II score 23.3 +/- 7.4) with
      severe sepsis or septic shock underwent TTE within 6 h of ICU admission, after 18
      to 32 h, and after resolution of shock. Left ventricular (LV) diastolic
      dysfunction was defined according to modified American Society of
      Echocardiography 2009 guidelines using E, A, and e' velocities; E/A and E/e'; and
      E deceleration time. Systolic dysfunction was defined as an ejection fraction <
      45%. RESULTS: Twenty-seven patients (36.5%) had diastolic dysfunction on initial
      echocardiogram, while 47 patients (61.8%) had diastolic dysfunction on at least
      one echocardiogram. Total mortality was 16.5%. The highest mortality (37.5%) was
      observed among patients with grade I diastolic dysfunction, an effect that
      persisted after controlling for age and APACHE II score. At time of initial TTE,
      central venous pressure (CVP) (11+/- 5 mmHg) did not differ among grades I-III,
      although patients with grade I received less intravenous fluid. CONCLUSIONS: LV
      diastolic dysfunction is common in septic patients. Grade I diastolic
      dysfunction, but not grades II and III, was associated with increased mortality.
      This finding may reflect inadequate fluid resuscitation in early sepsis despite
      an elevated CVP, suggesting a possible role for TTE in sepsis resuscitation.

PMID- 22870902
TI  - New therapeutic weapon in the treatment of refractory acute diverticulitis.

PMID- 22870901
TI  - Density of tumor-associated macrophages correlates with lymph node metastasis in
      papillary thyroid carcinoma.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) have recently been recognized as
      being important players in the tumoriogenesis of many cancers, including advanced
      thyroid cancer. However, a role in papillary thyroid carcinoma (PTC), the most
      prevalent thyroid cancer, has not been established. We hypothesized that TAMs
      also facilitate tumor progression in PTC. METHODS: We investigated TAMs density
      in both benign thyroid lesions and PTC tumors by CD68 immunostaining. CD68
      positive cell density was further associated with the clinicopathological
      characteristics of PTC patients. Finally, TAMs were isolated from PTC tumors and
      phenotyped by cytokine and receptor profiling. RESULTS: The overall density of
      TAMs was found to be significantly higher in PTC tumors, compared with thyroid
      goiter and follicular adenoma. The density of TAMs was positively associated with
      lymph node metastasis in TNM (tumor-node-metastasis) stages III/VI compared with
      stages I/II. No association was observed in other common tumor features,
      including the BRAF mutation. The isolated TAMs presented with high levels of M2
      associated cytokine and receptors, making M2 the predominant TAM phenotype.
      CONCLUSIONS: TAMs may play a functional role in the progression of PTC.

PMID- 22870903
TI  - The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and
      Ephedra sinica inhibits high-fat diet-induced hepatic steatosis via hepatic
      PPARalpha activation.
AB  - CONTEXT: The activation of peroxisome proliferator-activated receptor alpha
      (PPARalpha) target genes promotes hepatic oxidation of fatty acids. We
      hypothesized that Gyeongshingangjeehwan 18 (GGEx18), a mixture of three herbs,
      Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and
      Ephedra sinica Stapf (Ephedraceae), can regulate high-fat diet-induced hepatic
      steatosis through PPARalpha activation in the liver. OBJECTIVE: To investigate
      the effects of GGEx18 on obesity-related hepatic steatosis and the responsible
      mechanism. MATERIALS AND METHODS: The effects of GGEx18 on hepatic lipid
      accumulation, serum lipid profiles, and the expression of PPARalpha target genes
      were studied in high-fat diet-induced obese mice. The effects of GGEx18 on the
      expression of the PPARalpha targets and PPARalpha reporter gene activation were
      measured in NMu2Li liver cells. RESULTS: GGEx18 administration to obese mice for
      9 weeks markedly (p<0.05) decreased hepatic lipid accumulation compared with that
      in obese control mice. Serum triglyceride and total cholesterol levels were
      significantly (p <0.05) decreased by GGEx18. GGEx18 treatment increased the
      messenger RNA levels of PPARalpha target genes, which are responsible for fatty
      acid oxidation, in liver tissues. Consistent with the in vivo data, similar
      activation of genes was observed in GGEx18-treated NMu2Li liver cells. GGEx18
      also elevated PPARalpha reporter gene expression in NMu2Li cells. DISCUSSION AND
      CONCLUSION: These results suggest that GGEx18 prevents hepatic steatosis and
      hyperlipidemia in high-fat diet-induced obese mice, and this process may be
      mediated through PPARalpha activation in the liver.

PMID- 22870904
TI  - Intimate space within institutionalized birth: women's experiences birthing with
      doulas.
AB  - Childbirth in the American context is only peripherally conceptualized in the
      domain of the family and home, demonstrating the primacy of the biomedical model
      of childbirth in the institutional setting of the hospital. Medical research has
      found positive outcomes when women labor with 'doulas', paraprofessionals who are
      trained and experienced in childbirth. However, medical research has yet to
      explore the complexity of the labor experience of women with doulas, offering
      potential insights into how those positive outcomes may come about. Doulas define
      what they do in birth as 'holding the space'. This research explored what
      'holding the space' meant in terms of the experience of childbirth with women who
      employed doulas. The findings suggest that doulas' conceptualizations of the
      space of birth were framed in terms of creating/maintaining intimacy and that
      doulas and women maintained this intimate space even within the institutionalized
      medical-clinical birth experience. Implications of this research do not point to
      the generalization of doula attributes for implementation on an institutional
      level, but rather validate the contributions of external caregivers to producing
      positive outcomes.

PMID- 22870905
TI  - L-citrulline supplementation reverses the impaired airway relaxation in neonatal
      rats exposed to hyperoxia.
AB  - BACKGROUND: Hyperoxia is shown to impair airway relaxation via limiting L
      arginine bioavailability to nitric oxide synthase (NOS) and reducing NO
      production as a consequence. L-arginine can also be synthesized by L-citrulline
      recycling. The role of L-citrulline supplementation was investigated in the
      reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle
      (TSM). METHODS: Electrical field stimulation (EFS, 2-20 V)-induced relaxation was
      measured under in vitro conditions in preconstricted tracheal preparations
      obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen)
      for 7 days supplemented with L-citrulline or saline (in vitro or in vivo). The
      role of the L-citrulline/L-arginine cycle under basal conditions was studied by
      incubation of preparations in the presence of argininosuccinate synthase (ASS)
      inhibitor [alpha-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase
      inhibitor (ASL) succinate (1 mM) and/or NOS inhibitor [Nomega-nitro-L-arginine
      methyl ester; 100 MUM] with respect to the presence or absence of L-citrulline (2
      mM). RESULTS: Hyperoxia impaired the EFS-induced relaxation of TSM as compared to
      room air control (p < 0.001; 0.5 +/- 0.1% at 2 V to 50.6 +/- 5.7% at 20 V in
      hyperoxic group: 0.7 +/- 0.2 at 2 V to 80.0 +/- 5.6% at 20 V in room air group).
      Inhibition of ASS or ASL, and L-citrulline supplementation did not affect
      relaxation responses under basal conditions. However, inhibition of NOS
      significantly reduced relaxation responses (p < 0.001), which were restored to
      control level by L-citrulline. L-citrulline supplementation in vivo and in vitro
      also reversed the hyperoxia-impaired relaxation. The differences were significant
      (p <0.001; 0.8 +/- 0.3% at 2 V to 47.1 +/- 4.1% at 20 V without L-citrulline; 0.9
      +/- 0.3% at 2 V to 68.2 +/- 4.8% at 20 V with L-citrulline). Inhibition of ASS or
      ASL prevented this effect of L-citrulline. CONCLUSION: The results indicate the
      presence of an L-citrulline/L-arginine cycle in the airways of rat pups. L
      citrulline recycling does not play a major role under basal conditions in
      airways, but it has an important role under conditions of substrate limitations
      to NOS as a source of L-arginine, and L-citrulline supplementation reverses the
      impaired relaxation of airways under hyperoxic conditions.

PMID- 22870906
TI  - First clinical experience with IVR-CT system in the emergency room: positive
      impact on trauma workflow.
AB  - Recently, computed tomography (CT) has gained importance in the early diagnostic
      phase of trauma care in the emergency room. We implemented a new trauma workflow
      concept with CT in our emergency room that allows emergency therapeutic
      intervention without relocating the patient. Times from patient arrival to CT
      initiation, CT end, and definitive intervention were significantly shorter with
      our new protocol than were those with the conventional CT protocol. Our new
      workflow concept, which provides faster time to definitive intervention, appears
      to be effective.

PMID- 22870908
TI  - Denosumab versus zoledronic acid for treatment of bone metastases in men with
      castration-resistant prostate cancer: a cost-effectiveness analysis.
AB  - OBJECTIVE: Denosumab has been approved in the US for skeletal-related event (SRE)
      prevention in bone-metastatic prostate cancer on the basis of a phase III
      clinical trial in which denosumab reduced SREs relative to zoledronic acid.
      Overall survival, disease progression, and serious adverse events did not differ
      significantly between groups. This analysis assessed the cost-effectiveness of
      denosumab vs zoledronic acid in bone-metastatic prostate cancer from a US payer
      perspective. METHODS: A literature-based Markov model, wherein inputs were
      selected to reproduce clinical trial outcomes, was developed to estimate the
      survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug
      and administration costs for patients receiving denosumab or zoledronic acid over
      27 months. QALYs were estimated by assigning health-state utilities. SRE-related
      costs and utilities were literature-based. Outcomes were discounted 3% per annum,
      and model robustness was tested via scenario, univariate, and probabilistic
      sensitivity analyses. RESULTS: Denosumab resulted in fewer estimated SREs (
      0.241; 1.036 vs 1.277), more QALYs (0.0074; 0.9306 vs 0.9232), and lower SRE
      related costs (-$2340; $8824 vs $11,164), but higher drug-related costs ($10,181;
      $23,144 vs $12,963) and total costs ($7841; $31,968 vs $24,127) vs zoledronic
      acid. The base case estimated cost per QALY-gained was $1,058,741. CONCLUSION:
      This analysis was limited by the restricted availability of clinical data and the
      need to use projection methods beyond the trial time frame. However, a wide range
      of scenarios predicted denosumab to have an incremental cost/QALY gained above
      what may be considered acceptable value for money in the US. This raises
      important questions regarding the pharmacoeconomic value of denosumab in bone
      metastatic prostate cancer.

PMID- 22870907
TI  - Alternative Perspectives on Aging in Caenorhabditis elegans: Reactive Oxygen
      Species or Hyperfunction?
AB  - SIGNIFICANCE: The biological mechanisms at the heart of the aging process are a
      long-standing mystery. An influential theory has it that aging is the result of
      an accumulation of molecular damage, caused in particular by reactive oxygen
      species produced by mitochondria. This theory also predicts that processes that
      protect against oxidative damage (involving detoxification, repair, and turnover)
      protect against aging and increase lifespan. RECENT ADVANCES: However, recent
      tests of the oxidative damage theory, many using the short-lived nematode worm
      Caenorhabditis elegans, have often failed to support the theory. This motivates
      consideration of alternative models. One new theory, conceived by M.V.
      Blagosklonny, proposes that aging is caused by hyperfunction, that is,
      overactivity during adulthood of processes (particularly biosynthetic) that
      contribute to development and reproduction. Such hyperfunction can lead to
      hypertrophy-associated pathologies, which cause the age increase in death.
      CRITICAL ISSUES: Here we assess whether the hyperfunction theory is at all
      consistent with what is known about C. elegans aging, and conclude that it is. In
      particular, during adulthood, C. elegans shows a number of changes that may
      reflect pathology and/or hyperfunction. Such changes seem to contribute to death,
      at least in some cases (e.g., yolk accumulation). FUTURE DIRECTIONS: Our
      assessment suggests that the hyperfunction theory is a plausible alternative to
      the molecular damage theory to explain aging in C. elegans.

PMID- 22870909
TI  - Medical treatment of pruritus.
AB  - INTRODUCTION: The symptom of chronic pruritus (> 6 weeks of duration) represents
      a worldwide burden in patients. It is described as the most frequent symptom of
      the skin complaints and occurs in a broad variety of diseases. However, research
      on pruritus has been disregarded for a long time, most likely because pruritus
      used to be considered as a subtype of pain. AREAS COVERED: Although understanding
      of the epidemiology, clinic and neurobiology of acute and chronic pruritus has
      considerably expanded in the past years, the therapy of chronic pruritus patients
      remains challenging. The current guidelines suggest antihistamines, pain
      modulators, opioid receptor antagonist and antidepressants. Using this, a large
      number of patients experience relief but mostly no complete resolution. Recent
      experiences with neurokinin receptor 1 antagonists suggest that target-specific
      antipruritic drugs are of high efficacy and desirable in chronic pruritus
      treatments. EXPERT OPINION: New substances and classes of antipruritic drugs are
      highly needed. Promising candidates are next to neurokinin receptor 1
      antagonists, antagonists against the histamine 4 receptor, nerve growth factor
      receptor or gastrin-releasing peptide receptor.

PMID- 22870910
TI  - Stone clearance after extracorporeal shockwave lithotripsy in patients with
      solitary pure calcium oxalate stones smaller than 1.0 cm in the proximal ureter,
      with special reference to monohydrate and dihydrate content.
AB  - OBJECTIVE: The aim of this study was to assess stone-free rates following
      extracorporeal shockwave lithotripsy (ESWL) of pure calcium oxalate (CaOx) stones
      in the proximal ureter. MATERIAL AND METHODS: The investigators retrospectively
      examined 53 patients with 5-10 mm pure CaOx stones in the proximal ureter from
      the medical archives of 593 consecutive patients treated with ESWL. The
      compositions of calcium oxalate monohydrate (COM) and dihydrate (COD) in a given
      stone were determined by infrared spectrometry. Stone size, attenuation number
      and stone-to-skin distance (SSD) were measured using plain radiography and
      computed tomography (CT). ESWL success was evaluated by stone-free status after
      the first single session. RESULTS: On average, calculi were 8.0 * 5.3 mm in size,
      with an SSD of 11.0 cm. The mean CT attenuation value was 740.1 HU. Attenuation
      numbers correlated significantly with stone diameter (r = 0.49), but had no
      correlation with the stone content of COM or COD. A negative correlation was
      observed between COM and COD content (r = -0.925). With regard to patients'
      physical characteristics and COM and COD content, no differences were found
      between study subgroups with stone-free and residual status (n = 38 and 15,
      respectively). There were also no differences in clinical features between
      patient subgroups with COM- or COD-predominant stones (n = 22 and 31,
      respectively). CONCLUSION: The findings indicated that the differences in COM and
      COD content of CaOx stones had no impact on stone clearance after ESWL and that a
      favorable stone-free rate of the stones treated with ESWL may be achieved
      independently of CaOx hydration.

PMID- 22870911
TI  - The freetext matching algorithm: a computer program to extract diagnoses and
      causes of death from unstructured text in electronic health records.
AB  - BACKGROUND: Electronic health records are invaluable for medical research, but
      much information is stored as free text rather than in a coded form. For example,
      in the UK General Practice Research Database (GPRD), causes of death and test
      results are sometimes recorded only in free text. Free text can be difficult to
      use for research if it requires time-consuming manual review. Our aim was to
      develop an automated method for extracting coded information from free text in
      electronic patient records. METHODS: We reviewed the electronic patient records
      in GPRD of a random sample of 3310 patients who died in 2001, to identify the
      cause of death. We developed a computer program called the Freetext Matching
      Algorithm (FMA) to map diagnoses in text to the Read Clinical Terminology. The
      program uses lookup tables of synonyms and phrase patterns to identify diagnoses,
      dates and selected test results. We tested it on two random samples of free text
      from GPRD (1000 texts associated with death in 2001, and 1000 general texts from
      cases and controls in a coronary artery disease study), comparing the output to
      the U.S. National Library of Medicine's MetaMap program and the gold standard of
      manual review. RESULTS: Among 3310 patients registered in the GPRD who died in
      2001, the cause of death was recorded in coded form in 38.1% of patients, and in
      the free text alone in 19.4%. On the 1000 texts associated with death, FMA coded
      683 of the 735 positive diagnoses, with precision (positive predictive value)
      98.4% (95% confidence interval (CI) 97.2, 99.2) and recall (sensitivity) 92.9%
      (95% CI 90.8, 94.7). On the general sample, FMA detected 346 of the 447 positive
      diagnoses, with precision 91.5% (95% CI 88.3, 94.1) and recall 77.4% (95% CI
      73.2, 81.2), which was similar to MetaMap. CONCLUSIONS: We have developed an
      algorithm to extract coded information from free text in GP records with good
      precision. It may facilitate research using free text in electronic patient
      records, particularly for extracting the cause of death.

PMID- 22870912
TI  - Stereoselective isoxazolidine synthesis via copper-catalyzed alkene
      aminooxygenation.
AB  - Isoxazolidines are useful in organic synthesis, drug discovery, and chemical
      biology endeavors. A new stereoselective synthesis of methyleneoxy-substituted
      isoxazolidines is disclosed. The method involves copper-catalyzed
      aminooxygenation/cyclization of N-sulfonyl-O-butenyl hydroxylamines in the
      presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO) and O(2) and
      provides substituted isoxazolidines in excellent yields and
      diastereoselectivities. We also demonstrate selective mono N-O reduction followed
      by oxidation of the remaining N-O bond to reveal a 2-amino-gamma-lactone.
      Reduction of the gamma-lactone reveals the corresponding aminodiol.

PMID- 22870913
TI  - Farm-level associations with the shedding of Salmonella and antimicrobial
      resistant Salmonella in U.S. dairy cattle.
AB  - Salmonella enterica is the leading cause of foodborne-related deaths and
      hospitalizations within the United States. Infections caused by antimicrobial
      resistant (AMR) strains are associated with higher hospital costs and case
      fatality. The objective for this study was to determine the association of
      management practices with the recovery of Salmonella and AMR Salmonella on dairy
      herds. Individual adult cow fecal samples and/or composite fecal samples were
      collected from 265 dairy herds in 17 states. Samples were cultured for
      Salmonella, and the MIC was determined for 15 antimicrobials. Herds were
      classified as Salmonella positive if at least one isolate was recovered, and AMR
      Salmonella positive if at least one resistant isolate was recovered.
      Questionnaires regarding management practices were administered to herd
      operators, and a subset of practices was selected based on subject knowledge and
      prior research. Data on preventive and therapeutic antimicrobial usage were
      included in the analysis. Logistic regression models were used to determine which
      practices were significantly (p<0.05) associated with each herd classification. A
      total of 124 and 25 herds were classified as Salmonella positive and AMR
      Salmonella positive, respectively. Variables significantly associated with
      Salmonella-positive herds included using sprinklers or misters for heat abatement
      (OR=2.8; CI: 1.6-4.9), feeding anionic salts to cows (OR=1.9; CI: 1.1-3.5), and
      feeding ionophores to cows (OR=2.1; CI: 1.2-3.7). Herds that used a
      broadcast/solid spread had lower odds (OR=0.26; CI: 0.11-0.63) of being
      Salmonella positive. Herds with at least one resistant isolate were more likely
      to have used composted/dried manure for bedding relative to herds with only
      susceptible isolates (OR=3.6; CI: 1.2-11.0). These results can be useful to focus
      additional research aimed at decreasing the prevalence of Salmonella and AMR
      Salmonella on U.S. dairy herds.

PMID- 22870914
TI  - Activity enhancement of the synthetic syrbactin proteasome inhibitor hybrid and
      biological evaluation in tumor cells.
AB  - Syrbactins belong to a recently emergent class of bacterial natural product
      inhibitors that irreversibly inhibit the proteasome of eukaryotes by a novel
      mechanism. The total syntheses of the syrbactin molecules syringolin A,
      syringolin B, and glidobactin A have been achieved, which allowed the preparation
      of syrbactin-inspired derivatives, such as the syringolin A-glidobactin A hybrid
      molecule (SylA-GlbA). To determine the potency of SylA-GlbA, we employed both in
      vitro and cell culture-based proteasome assays that measure the subcatalytic
      chymotrypsin-like (CT-L), trypsin-like (T-L), and caspase-like (C-L) activities.
      We further studied the inhibitory effects of SylA-GlbA on tumor cell growth using
      a panel of multiple myeloma, neuroblastoma, and ovarian cancer cell lines and
      showed that SylA-GlbA strongly blocks the activity of NF-kappaB. To gain more
      insights into the structure-activity relationship, we cocrystallized SylA-GlbA in
      complex with the proteasome and determined the X-ray structure. The electron
      density map displays covalent binding of the Thr1O(gamma) atoms of all active
      sites to the macrolactam ring of the ligand via ether bond formation, thus
      providing insights into the structure-activity relationship for the improved
      affinity of SylA-GlbA for the CT-L activity compared to those of the natural
      compounds SylA and GlbA. Our study revealed that the novel synthetic syrbactin
      compound represents one of the most potent proteasome inhibitors analyzed to date
      and therefore exhibits promising properties for improved drug development as an
      anticancer therapeutic.

PMID- 22870917
TI  - Making sense of boron-rich binary Be-B phases.
AB  - There is much uncertainty in the literature about the structure of several Be-B
      phases between 20 and 33 atom % Be. We clarify the structural choices in this
      region of the phase diagram, proposing structural candidates obtained from a
      combination of chemical intuition and unbiased solid-state structure searches. In
      particular, we discuss the structural, dynamical, and electronic properties of
      the ground states of the BeB(2), BeB(3), and BeB(4) phases, as well as those of
      the complex (and superconducting) "BeB(2.75)" phase. For the latter, we find the
      polyhedral borane cluster electron-counting approach very useful to explain its
      electronic structure. We can also make sense of the partial and mixed occupancies
      in the structure by looking at the cavities in a parent structure. A Be(29)B(81)
      stoichiometry seems most reasonable for the ground state of this phase. The
      electronic structure points to a region of stability for three additional
      electrons per unit cell, a 1% difference in total electron count. For BeB(2),
      which is usually studied computationally in the AlB(2) structure type, we find
      several other structure types that are more stable, all essentially Zintl phases
      with 4-connected boron networks. New structure types are also predicted for
      BeB(3) and BeB(4) as well.

PMID- 22870916
TI  - Neighbourhood socioeconomic inequalities in incidence of acute myocardial
      infarction: a cohort study quantifying age- and gender-specific differences in
      relative and absolute terms.
AB  - BACKGROUND: Socioeconomic status has a profound effect on the risk of having a
      first acute myocardial infarction (AMI). Information on socioeconomic
      inequalities in AMI incidence across age-gender-groups is lacking. Our objective
      was to examine socioeconomic inequalities in the incidence of AMI considering
      both relative and absolute measures of risk differences, with a particular focus
      on age and gender. METHODS: We identified all patients with a first AMI from 1997
      to 2007 through linked hospital discharge and death records covering the Dutch
      population. Relative risks (RR) of AMI incidence were estimated by mean
      equivalent household income at neighbourhood-level for strata of age and gender
      using Poisson regression models. Socioeconomic inequalities were also shown
      within the stratified age-gender groups by calculating the total number of events
      attributable to socioeconomic disadvantage. RESULTS: Between 1997 and 2007,
      317,564 people had a first AMI. When comparing the most deprived socioeconomic
      quintile with the most affluent quintile, the overall RR for AMI was 1.34 (95 %
      confidence interval (CI): 1.32-1.36) in men and 1.44 (95 % CI: 1.42-1.47) in
      women. The socioeconomic gradient decreased with age. Relative socioeconomic
      inequalities were most apparent in men under 35 years and in women under 65
      years. The largest number of events attributable to socioeconomic inequalities
      was found in men aged 45-74 years and in women aged 65-84 years. The total
      proportion of AMIs that was attributable to socioeconomic inequalities in the
      Dutch population of 1997 to 2007 was 14 % in men and 18 % in women. CONCLUSIONS:
      Neighbourhood socioeconomic inequalities were observed in AMI incidence in the
      Netherlands, but the magnitude across age-gender groups depended on whether
      inequality was expressed in relative or absolute terms. Relative socioeconomic
      inequalities were high in young persons and women, where the absolute burden of
      AMI was low. Absolute socioeconomic inequalities in AMI were highest in the age
      gender groups of middle-aged men and elderly women, where the number of cases was
      largest.

PMID- 22870918
TI  - Bedside ultrasound diagnosis of atraumatic bladder rupture in an alcohol
      intoxicated patient: a case report.
AB  - Most commonly, patients who present to the emergency department with a history
      and physical examination suggestive of urinary bladder rupture report a preceding
      traumatic event. Spontaneous atraumatic bladder rupture is relatively uncommon,
      but can occur in the context of a recent alcohol binge. The alcohol-intoxicated
      patient presents diagnostic and therapeutic challenges to the emergency physician
      (EP) that take on additional urgency given the high mortality of unrecognized
      bladder rupture. This case report reviews bladder anatomy, the unique
      physiological changes in the alcohol-intoxicated patient, and the high mortality
      rate of a ruptured urinary bladder. We review the historical diagnostic imaging
      options followed by a discussion of how bedside ultrasound could expedite
      diagnosis and management. We present the case of a patient with spontaneous
      atraumatic rupture of the urinary bladder after a recent alcohol binge. Bedside
      ultrasound was utilized by the EP to determine the need for emergent surgical
      consultation and intervention. We recommend that EPs consider bladder rupture in
      their initial evaluation of patients presenting with nonspecific abdominal pain
      in the context of recent alcohol intoxication. When using bedside ultrasound to
      evaluate the pelvis, the presence of anterior or posterior vesicular fluid
      collections, the loss of normal pelvic landmarks, or irregularities in the
      bladder wall may increase the EPs suspicion for this disease entity and expedite
      time-sensitive management.

PMID- 22870919
TI  - CC chemokine ligand 2 upregulates the current density and expression of TRPV1
      channels and Nav1.8 sodium channels in dorsal root ganglion neurons.
AB  - BACKGROUND: Inflammation or nerve injury-induced upregulation and release of
      chemokine CC chemokine ligand 2 (CCL2) within the dorsal root ganglion (DRG) is
      believed to enhance the activity of DRG nociceptive neurons and cause
      hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1) and
      tetrodotoxin (TTX)-resistant Na(v)1.8 sodium channels play an essential role in
      regulating the excitability and pain transmission of DRG nociceptive neurons. We
      therefore tested the hypothesis that CCL2 causes peripheral sensitization of
      nociceptive DRG neurons by upregulating the function and expression of TRPV1 and
      Nav1.8 channels. METHODS: DRG neuronal culture was prepared from 3-week-old
      Sprague-Dawley rats and incubated with various concentrations of CCL2 for 24 to
      36 hours. Whole-cell voltage-clamp recordings were performed to record TRPV1
      agonist capsaicin-evoked inward currents or TTX-insensitive Na(+) currents from
      control or CCL2-treated small DRG sensory neurons. The CCL2 effect on the mRNA
      expression of TRPV1 or Na(v)1.8 was measured by real-time quantitative RT-PCR
      assay. RESULTS: Pretreatment of CCL2 for 24 to 36 hours dose-dependently (EC(50)
      value = 0.6 +/- 0.05 nM) increased the density of capsaicin-induced currents in
      small putative DRG nociceptive neurons. TRPV1 mRNA expression was greatly
      upregulated in DRG neurons preincubated with 5 nM CCL2. Pretreating small DRG
      sensory neurons with CCL2 also increased the density of TTX-resistant Na(+)
      currents with a concentration-dependent manner (EC(50) value = 0.7 +/- 0.06 nM).
      The Na(v)1.8 mRNA level was significantly increased in DRG neurons pretreated
      with CCL2. In contrast, CCL2 preincubation failed to affect the mRNA level of TTX
      resistant Nav1.9. In the presence of the specific phosphatidylinositol-3 kinase
      (PI3K) inhibitor LY294002 or Akt inhibitor IV, CCL2 pretreatment failed to
      increase the current density of capsaicin-evoked inward currents or TTX
      insensitive Na(+) currents and the mRNA level of TRPV1 or Na(v)1.8. CONCLUSIONS:
      Our results showed that CCL2 increased the function and mRNA level of TRPV1
      channels and Na(v)1.8 sodium channels in small DRG sensory neurons via activating
      the PI3K/Akt signaling pathway. These findings suggest that following tissue
      inflammation or peripheral nerve injury, upregulation and release of CCL2 within
      the DRG could facilitate pain transmission mediated by nociceptive DRG neurons
      and could induce hyperalgesia by upregulating the expression and function of
      TRPV1 and Na(v)1.8 channels in DRG nociceptive neurons.

PMID- 22870920
TI  - Pairwise protein expression classifier for candidate biomarker discovery for
      early detection of human disease prognosis.
AB  - BACKGROUND: An approach to molecular classification based on the comparative
      expression of protein pairs is presented. The method overcomes some of the
      present limitations in using peptide intensity data for class prediction for
      problems such as the detection of a disease, disease prognosis, or for predicting
      treatment response. Data analysis is particularly challenging in these situations
      due to sample size (typically tens) being much smaller than the large number of
      peptides (typically thousands). Methods based upon high dimensional statistical
      models, machine learning or other complex classifiers generate decisions which
      may be very accurate but can be complex and difficult to interpret in simple or
      biologically meaningful terms. A classification scheme, called ProtPair, is
      presented that generates simple decision rules leading to accurate classification
      which is based on measurement of very few proteins and requires only relative
      expression values, providing specific targeted hypotheses suitable for
      straightforward validation. RESULTS: ProtPair has been tested against clinical
      data from 21 patients following a bone marrow transplant, 13 of which progress to
      idiopathic pneumonia syndrome (IPS). The approach combines multiple peptide pairs
      originating from the same set of proteins, with each unique peptide pair
      providing an independent measure of discriminatory power. The prediction rate of
      the ProtPair for IPS study as measured by leave-one-out CV is 69.1%, which can be
      very beneficial for clinical diagnosis as it may flag patients in need of closer
      monitoring. The "top ranked" proteins provided by ProtPair are known to be
      associated with the biological processes and pathways intimately associated with
      known IPS biology based on mouse models. CONCLUSIONS: An approach to biomarker
      discovery, called ProtPair, is presented. ProtPair is based on the differential
      expression of pairs of peptides and the associated proteins. Using mass
      spectrometry data from "bottom up" proteomics methods, functionally related
      proteins/peptide pairs exhibiting co-ordinated changes expression profile are
      discovered, which represent a signature for patients progressing to various
      disease conditions. The method has been tested against clinical data from
      patients progressing to idiopthatic pneumonia syndrome (IPS) following a bone
      marrow transplant. The data indicates that patients with improper regulation in
      the concentration of specific acute phase response proteins at the time of bone
      marrow transplant are highly likely to develop IPS within few weeks. The results
      lead to a specific set of protein pairs that can be efficiently verified by
      investigating the pairwise abundance change in independent cohorts using ELISA or
      targeted mass spectrometry techniques. This generalized classifier can be
      extended to other clinical problems in a variety of contexts.

PMID- 22870921
TI  - Diagnostic accuracy of the STRATIFY clinical prediction rule for falls: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The STRATIFY score is a clinical prediction rule (CPR) derived to
      assist clinicians to identify patients at risk of falling. The purpose of this
      systematic review and meta-analysis is to determine the overall diagnostic
      accuracy of the STRATIFY rule across a variety of clinical settings. METHODS: A
      literature search was performed to identify all studies that validated the
      STRATIFY rule. The methodological quality of the studies was assessed using the
      Quality Assessment of Diagnostic Accuracy Studies tool. A STRATIFY score of >=2
      points was used to identify individuals at higher risk of falling. All included
      studies were combined using a bivariate random effects model to generate pooled
      sensitivity and specificity of STRATIFY at >=2 points. Heterogeneity was assessed
      using the variance of logit transformed sensitivity and specificity. RESULTS:
      Seventeen studies were included in our meta-analysis, incorporating 11,378
      patients. At a score >=2 points, the STRATIFY rule is more useful at ruling out
      falls in those classified as low risk, with a greater pooled sensitivity estimate
      (0.67, 95% CI 0.52-0.80) than specificity (0.57, 95% CI 0.45 - 0.69). The
      sensitivity analysis which examined the performance of the rule in different
      settings and subgroups also showed broadly comparable results, indicating that
      the STRATIFY rule performs in a similar manner across a variety of different 'at
      risk' patient groups in different clinical settings. CONCLUSION: This systematic
      review shows that the diagnostic accuracy of the STRATIFY rule is limited and
      should not be used in isolation for identifying individuals at high risk of falls
      in clinical practice.

PMID- 22870922
TI  - Postoperative changes in spatial localization following exotropia surgery.
AB  - PURPOSE: To measure changes in spatial localization following exotropia surgery
      using a computer touch-screen method of measurement. METHODS: Enrolled in the
      study were 60 exotropia patients, all of whom had undergone corrective muscle
      surgeries under general anesthesia: 37 patients had undergone unilateral lateral
      rectus or bilateral lateral rectus muscle recession procedures (recession group)
      and 23 patients had undergone unilateral lateral and medial rectus muscle
      resection (R&R), or unilateral medial rectus resection only (resection group). We
      evaluated spatial localization by having patients point to targets on a computer
      touch-screen before surgery, and 1 day and 1 month after surgery. The pointing
      error, Deltap, is defined as the difference between the actual location of the
      target and the pointed-to location of the target by unsigned value, was recorded
      as the mean of five tests. We compared the extent of postoperative changes in
      Deltap between the two groups. RESULTS: The mean Deltap before surgery did not
      differ statistically between the two groups (p = 0.93). One day after surgery,
      however, the postoperative change in Deltap of the resection group compared with
      that of the recession group (2.0 +/- 0.7 degrees  and 0.4 +/- 0.5 degrees ,
      respectively) was significant (p = 0.01 and p = 0.86 respectively). CONCLUSIONS:
      The ability for spatial localization is decreased in patients immediately
      following medial rectus resection, but is regained by 1 month following surgery.

PMID- 22870923
TI  - Mitigating role of quercetin against sodium fluoride-induced oxidative stress in
      the rat brain.
AB  - CONTEXT: Quercetin is a well known aglycone flavonoid that is widely found in
      different food sources. OBJECTIVE: In this study, the in vivo neuroprotective
      potential of quercetin against sodium fluoride-induced oxidative stress was
      evaluated. MATERIALS AND METHODS: Wistar rats were divided into five treatment
      groups and then subjected to daily intraperitoneally treatment with quercetin (at
      10 and 20 mg/kg body weight), vitamin C (at 10 mg/kg), or vehicle. After a 1 week
      treatment period, all groups except saline treated (normal group), were
      intoxicated with sodium fluoride (NaF) for 1 week. Rat brains were then removed
      and homogenized for measurement of antioxidant markers including superoxide
      dismutase (SOD), reduced glutathione, catalase, and lipid peroxidation final
      products. RESULTS: The thiobarbituric acid reactive substances (TBARS) levels in
      the heart homogenate of sodium fluoride treated rats (42.04 +/- 2.14 nmol MDA
      eq/g tissue) increased compared to the normal rats (35.99 +/- 1.08 nmol MDA eq/g
      tissue). Animals which were pretreated with quercetin at 20 mg/kg for 1 week
      prior to sodium fluoride intoxication showed significant reduction in the TBARS
      level (36.13 +/- 1.12 nmol MDA eq/g tissue). Also, pretreatment with quercetin
      (20 mg/kg) restored the SOD and catalase activities and modified the level of
      reduced glutathione compared with the control group (p > 0.05). DISCUSSION AND
      CONCLUSION: The present study revealed a potent neuroprotective potential of
      quercetin against NaF-induced toxicity.

PMID- 22870924
TI  - Necrotizing soft tissue infection of the breast: case report and literature
      review.
AB  - BACKGROUND: Necrotizing soft tissue infection (NSTI) is characterized by
      progressive infectious gangrene of the skin and subcutaneous tissue. Its
      treatment involves intensive care, broad-spectrum antibiotic therapy, and full
      debridement. METHODS: We present two cases of NSTI of the breast, adding these
      cases to the 14 described in the literature, reviewing the characteristics and
      evolution of all cases. CASE REPORT: On the fourth day after mastectomy, a 59
      year-old woman with ulcerated breast cancer developed Type I NSTI caused by
      Pseudomonas aeruginosa, which had a favorable evolution after debridement and
      broad-spectrum antibiotics. The second patient was a 57-year-old woman submitted
      to a mastectomy and axillary dissection, who had recurrent seromas. On the 32nd
      post-operative day, after a seroma puncture, she developed Type II NSTI caused by
      beta-hemolytic streptococci. She developed sepsis and died on the tenth day after
      debridement, intensive care, and broad-spectrum antibiotics. The cases are the
      first description of breast NSTI after mammary seroma aspiration and the first
      report of this condition caused by P. aeruginosa. CONCLUSION: Necrotizing soft
      tissue infection is rare in breast tissue. It frequently is of Type II, occurring
      mainly after procedures in patients with breast cancer. The surgeon's
      participation in controlling the focus of the infection is of fundamental
      importance, and just as important are broad-spectrum antibiotic therapy and
      support measures, such as maintenance of volume, correction of electrolytic
      disorders, and treatment of sepsis and septic shock. Once the infection has been
      brought under control, skin grafting or soft tissue flaps can be considered. The
      mortality rate in breast NSTI is 18.7%, all deaths being in patients with the
      fulminant Type II form. Surgical oncologists need to be alert to the possibility
      of this rare condition.

PMID- 22870925
TI  - Accurate and reproducible determination of lignin molar mass by acetobromination.
AB  - The accurate and reproducible determination of lignin molar mass by using size
      exclusion chromatography (SEC) is challenging. The lignin association effects,
      known to dominate underivatized lignins, have been thoroughly addressed by
      reaction with acetyl bromide in an excess of glacial acetic acid. The combination
      of a concerted acetylation with the introduction of bromine within the lignin
      alkyl side chains is thought to be responsible for the observed excellent
      solubilization characteristics acetobromination imparts to a variety of lignin
      samples. The proposed methodology was compared and contrasted to traditional
      lignin derivatization methods. In addition, side reactions that could possibly be
      induced under the acetobromination conditions were explored with native softwood
      (milled wood lignin, MWL) and technical (kraft) lignin. These efforts lend
      support toward the use of room temperature acetobromination being a facile,
      effective, and universal lignin derivatization medium proposed to be employed
      prior to SEC measurements.

PMID- 22870926
TI  - Transition-metal-free electrophilic amination of arylboroxines.
AB  - A transition-metal-free strategy to construct C(sp(2))-N bonds using
      arylboroxines and O-benzoyl hydroxylamines as coupling partners has been
      developed. This transformation provides a useful method to access various
      aromatic amines.

PMID- 22870927
TI  - Association between low serum free thyroxine concentrations and coronary artery
      calcification in healthy euthyroid subjects.
AB  - BACKGROUND: Considerable evidence suggests that hypothyroidism could promote
      atherosclerotic vascular changes. We planned this study to investigate whether
      serum free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels are
      associated with coronary artery calcification measured in healthy euthyroid
      subjects. METHODS: A cross-sectional analysis was performed among subjects who
      visited our hospital for a health checkup. Among 1849 subjects, 669 (mean age
      55.3+/-8.8 years; 392 men) with FT4 and TSH in the normal ranges were included
      after excluding those with diabetes, a history of current smoking and
      cardiovascular disease (CVD), or the use of drugs for hypertension, antithyroid
      drugs, or thyroid hormone preparations. Coronary artery calcium scores (CACS)
      were measured by multi-detector computed tomography. RESULTS: Subjects with a
      CACS >100 had lower FT4 levels than those with a lower CACS (p=0.017), whereas no
      difference was observed in the TSH levels among CACS categories. FT4 levels had
      an odds ratio of 0.06 for high CACS (95% confidence interval=0.01-0.74; p=0.028)
      after the adjustment for CVD risk factors. In multivariate regression analysis,
      CACS was negatively correlated with FT4 levels (beta=-0.823, p=0.032), and the
      inverse association between FT4 and CACS remained significant only in men
      (p=0.011). CONCLUSION: FT4 levels were inversely associated with coronary artery
      calcification in euthyroid healthy subjects, especially in men independent of
      conventional CVD risk factors. Further studies are needed to validate whether
      subjects with decreased FT4 levels within the normal reference range are at a
      high CVD risk and have poor cardiovascular outcomes.

PMID- 22870928
TI  - Early detection and quantification of mutations in the tyrosine kinase domain of
      chimerical BCR-ABL1 gene combining high-resolution melting analysis and mutant
      allele specific quantitative polymerase chain reaction.
AB  - BCR-ABL1 point mutations are the most common cause of resistance in patients with
      chronic myeloid leukemia (CML) who fail or lose response to tyrosine kinase
      inhibitors. We have developed a rapid method to screen BCR-ABL1 mutations by high
      resolution melting (HRM). We designed a strategy based on amplification
      refractory mutational system-quantitative polymerase chain reaction (ARMS-qPCR)
      to identify and quantify several clinically relevant mutations. From 856 patients
      with CML studied during 2 years in our laboratory, we selected 32 who showed
      persistent levels of BCR-ABL1 transcripts (>0.1%) in at least two consecutive
      studies. Using our strategy, we identified mutations in 11/32 cases (34.4%),
      while only two of them (6.2%) were detectable by sequencing. Furthermore, we were
      able to estimate the timing and dynamics of mutated clones, evaluating
      retrospective samples from the same patient. In cases with lack or loss of
      molecular response this analysis might be useful for designing early therapeutic
      strategies.

PMID- 22870929
TI  - Comparison of various criteria in interpreting end of therapy F-18 labeled
      fluorodeoxyglucose positron emission tomography/computed tomography in patients
      with aggressive non-Hodgkin lymphoma.
AB  - Various interpretation criteria exist to assess end of therapy F-18 labeled
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
      in lymphoma. This study was carried out to compare these criteria. Data of 69
      patients with aggressive non-Hodgkin lymphoma (AGR-NHL) who underwent FDG PET/CT
      at the end of therapy and were followed up for a minimum period of 1 year (median
      follow-up period 17 months) were evaluated. Twenty-eight of the 69 patients were
      found to have residual/recurrent disease during follow-up. The accuracy for
      predicting residual disease of International Harmonization Project (IHP)
      criteria, London criteria and Gallamini criteria was 71.0%, 84.0% and 88.4%,
      respectively. Gallamini and London criteria had greater accuracies in predicting
      residual disease than IHP criteria (p = 0.0001). The major difference in accuracy
      was due to the low positive predictive value of IHP criteria. Positive predictive
      values (PPVs) of both London and Gallamini criteria (79.3% and 88.5%,
      respectively) were high when compared with that of IHP criteria (60.5%) (p =
      0.001). Negative predictive values (NPVs) were similar for all the criteria. In
      conclusion, Gallamini and London criteria had higher accuracy when interpreting
      end of therapy FDG PET/CT studies in AGR-NHL. London criteria can be used
      preferentially over Gallamini criteria because of simplicity in interpretation
      and reproducibility.

PMID- 22870930
TI  - Evaluation of antigen detection and polymerase chain reaction for diagnosis of
      amoebic liver abscess in patients on anti-amoebic treatment.
AB  - BACKGROUND: Diagnosis of amoebic liver abscess (ALA) in patients on anti-amoebic
      drugs is difficult. There is scanty data on this issue using Entamoeba
      histolytica (E. histolytica) lectin antigen and polymerase chain reaction (PCR).
      We studied utility of lectin antigen, PCR, and IgG antibody in diagnosis of liver
      abscess in patients on anti-amoebic treatment. Liver aspirate of 200 patients, of
      which 170 had anti-amoebic drug prior to drainage, was tested for E. histolytica
      lectin antigen by (ELISA), PCR, bacterial culture, and serum IgG antibody by
      (ELISA). Classification of abscesses was based on result of anti-amoebic IgG
      antibody and bacterial culture, E. histolytica PCR and bacterial culture, and E.
      histolytica lectin antigen and bacterial culture. FINDINGS: Using anti-amoebic
      IgG antibody and bacterial culture, 136/200 (68.0%) were classified as ALA,
      12/200 (6.0%) as pyogenic liver abscess (PLA), 29/200 (14.5%) as mixed infection,
      and 23/200 (11.5%) remained unclassified. Using amoebic PCR and bacterial culture
      151/200 (75.5%) were classified as ALA, 25/200 (12.5%) as PLA, 16/200 (8.0%) as
      mixed infection, and 8/200 (4.0%) remained unclassified. With E. histolytica
      lectin antigen and bacterial culture, 22/200 (11.0%) patients were classified as
      ALA, 39/200 (19.5%) as PLA, 2/200 (1.0%) as mixed infection, and 137/200 (68.5%)
      remained unclassified. CONCLUSIONS: E. histolytica lectin antigen was not
      suitable for classification of ALA patients who had prior anti-amoebic treatment.
      However, PCR may be used as alternative test to anti-amoebic antibody in
      diagnosis of ALA.

PMID- 22870931
TI  - Hematopoietic effect of Bacillus subtilis-fermented antler extract on
      phenylhydrazine-induced hemolytic anemia in Sprague-Dawley rats.
AB  - This study examined the effect of fermentation on the ability of antler to act as
      a stimulator of hematopoietic activity. Hemolytic anemia was induced by
      phenylhydrazine (PHZ) in female Sprague-Dawley rats. The vehicle or antler
      extract (nonfermented or fermented) mixed in drinking water was administered from
      Days 2 to 15 after PHZ injection. On Day 15, red blood cell counts in the
      fermented antler group (6.33*106/MUL) were significantly higher than those in the
      nonfermented antler group (5.90*106/MUL) (P<.05), and rats treated with fermented
      antler extract tended to have higher hemoglobin compared with rats treated with
      nonfermented antler extract, but not significantly. In addition, rats treated
      with fermented antler extract had slightly lower serum erythropoietin levels
      compared with nonfermented antler extract, which were not statistically different
      from serum erythropoietin levels of nonanemic rats. We conclude therefore that
      the hematopoietic activity of antler might be increased by the fermentation
      process.

PMID- 22870933
TI  - A spatial analysis of the expanding roles of nurses in general practice.
AB  - BACKGROUND: Changes to the workforce and organisation of general practice are
      occurring rapidly in response to the Australian health care reform agenda, and
      the changing nature of the medical profession. In particular, the last five years
      has seen the rapid introduction and expansion of a nursing workforce in
      Australian general practices. This potentially creates pressures on current
      infrastructure in general practice. METHOD: This study used a mixed methods,
      'rapid appraisal' approach involving observation, photographs, and interviews.
      RESULTS: Nurses utilise space differently to GPs, and this is part of the
      diversity they bring to the general practice environment. At the same time their
      roles are partly shaped by the ways space is constructed in general practices.
      CONCLUSION: The fluidity of nursing roles in general practice suggests that
      nurses require a versatile space in which to maximize their role and contribution
      to the general practice team.

PMID- 22870934
TI  - Constrained bonding environment in the Michaelis complex of Trypanosoma cruzi
      uridine phosphorylase.
AB  - The transition state for the Trypanosoma cruzi uridine phosphorylase (TcUP)
      reaction has an expanded S(N)2 character. We used binding isotope effects (BIE's)
      to probe uridine distortion in the complex with TcUP and sulfate to mimic the
      Michaelis complex. Inverse 1'-(3)H and 5'-(3)H BIE's indicate a constrained
      bonding environment of these groups in the complex. Quantum chemical modeling
      identified a uridine conformer whose calculated BIE's match the experimental
      values. This conformer differs in sugar pucker and uracil orientation from the
      unbound conformer and the transition-state structure. These results support
      ground-state stabilization in the Michaelis complex.

PMID- 22870932
TI  - Angiogenesis in the infarcted myocardium.
AB  - SIGNIFICANCE: Proangiogenic therapy appeared a promising strategy for the
      treatment of patients with acute myocardial infarction (MI), as de novo formation
      of microvessels, has the potential to salvage ischemic myocardium at early stages
      after MI, and is also essential to prevent the transition to heart failure
      through the control of cardiomyocyte hypertrophy and contractility. RECENT
      ADVANCES: Exciting preclinical studies evaluating proangiogenic therapies for MI
      have prompted the initiation of numerous clinical trials based on protein or gene
      transfer delivery of growth factors and administration of stem/progenitor cells,
      mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed
      results in patients with acute MI. CRITICAL ISSUES: Even though methodological
      caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs.
      gene transfer) and stem/progenitor cells or isolation/culture procedure for
      regenerative cells might partially explain the failure of such trials, it appears
      that delivery of a single growth factor or cell type does not support
      angiogenesis sufficiently to promote cardiac repair. FUTURE DIRECTIONS:
      Optimization of proangiogenic therapies might include stimulation of both
      angiogenesis and vessel maturation and/or the use of additional sources of
      stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling
      of the mechanisms of angiogenesis, vessel maturation, and endothelial
      cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging
      pathways, as well as a better understanding of how cardiovascular risk factors
      impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly
      pave the way for the development of novel and hopefully efficient angiogenesis
      targeting therapeutics for the treatment of acute MI.

PMID- 22870935
TI  - Intra-articular corrective osteotomy for malunited Hoffa fracture: A case report.
AB  - Hoffa fracture, an isolated coronal plane fracture of the posterior aspect of
      the femoral condyle, is known as an unstable, intra-articular fracture, and
      therefore, operative treatment is recommended. However, insufficient open
      reduction or failure of fixation may lead to malunion. We performed intra
      articular corrective osteotomy for a malunited Hoffa fracture in a 31-year-old
      man and obtained good functional and radiographic results. This report suggests
      that intra-articular corrective osteotomy for malunited Hoffa fracture offers a
      good outcome and should be considered as salvage treatment.

PMID- 22870936
TI  - Incomplete desorption of liquid excipients reduces the in vitro and in vivo
      performance of self-emulsifying drug delivery systems solidified by adsorption
      onto an inorganic mesoporous carrier.
AB  - The purpose of the current study was to provide a mechanistic basis for in vitro
      and in vivo performance differences between lipid-based formulations solidified
      by adsorption onto a high surface area material and their respective liquid
      (i.e., nonadsorbed) counterparts. Two self-emulsifying formulations (based on
      either medium-chain or long-chain lipids) of the poorly water-soluble drug
      danazol were solidified by adsorption onto Neusilin US2. Liquid and adsorbed
      lipid-based formulations were subjected to in vitro dispersion-digestion tests,
      and additional in vitro experiments were performed to elucidate the cause of
      performance differences. The bioavailability of danazol after oral administration
      to rats was also assessed. The percentage of the dose solubilized in the aqueous
      phase during in vitro dispersion-digesting was ~35%  lower for the adsorbed
      formulations when compared to their liquid counterparts. This trend was also
      reflected in vivo, where the bioavailability of danazol after administration of
      the adsorbed formulations was ~50% lower than that obtained after administration
      of the equivalent liquid formulation. Incomplete desorption of the microemulsion
      preconcentrate from the carrier on dispersion-digestion was identified as the
      main contributor to the reduced pharmaceutical performance of the adsorbed
      formulations. The results of the current study indicate that solidification of
      lipid-based formulations through adsorption onto a high surface area carrier may
      limit formulation (and drug) release in vivo and thereby reduce oral
      bioavailability.

PMID- 22870937
TI  - Regioselective diversification of a cardiac glycoside, lanatoside C, by
      organocatalysis.
AB  - Acylation of lanatoside C in the presence of organocatalyst 5 gave the C(4'''')-O
      acylate in up to 90% regioselectivity (catalyst-controlled regioselectivity).
      Various functionalized acyl groups can be introduced at the C(4'''')-OH by a
      mixed anhydride method in the presence of 5 or the related organocatalyst. On the
      other hand, DMAP-catalyzed acylation of lanatoside C gave the C(3'''')-O-acylate
      in up to 97% regioselectivity (substrate-controlled regioselectivity). Thus,
      diverse regioselective introduction of acyl groups among eight free hydroxy
      groups of lanatoside C was achieved.

PMID- 22870938
TI  - Antimicrobial-resistant Campylobacter in the food chain in Mexico.
AB  - We describe prevalence and antimicrobial susceptibility results for thermophilic
      Campylobacter isolates collected from humans, food, and food-animals in an
      integrated food chain surveillance network in Mexico. From 2003 to 2006, stool
      samples were collected from children with diarrhea at state sentinel hospitals.
      Concurrently, fecal samples from asymptomatic children in kindergartens, as well
      as raw chicken, pork and beef from retail outlets, and food-animal intestines
      from slaughterhouses were all collected in 65 cities from four different states.
      C. jejuni was identified with a standardized hippurate test. Hippurate negative,
      indoxyl acetate positive isolates were classified as Campylobacter spp.
      Susceptibility testing was performed by agar dilution according to Clinical and
      Laboratory Standards Institute guidelines. A total of 1,259 C. jejuni and 1,797
      Campylobacter spp. isolates were recovered from 11,811 samples. Chicken was
      significantly more contaminated for both intestinal samples (93.6%) and meat
      products (58.3%), compared with swine (71.4%)/pork (14.6%) samples, and cattle
      (25.1%)/beef (5.3%) samples (p<0.001). Campylobacter was recovered from 5.1% of
      children with diarrhea and from 3.2% of asymptomatic children. Chicken was
      significantly more likely to harbor ciprofloxacin-resistant C. jejuni (85.8%)
      than swine (62.5%, OR=3.6), cattle (39.8%, OR=9.3), or humans (58.2%, OR=4.4). No
      significant differences were found for ciprofloxacin-resistant Campylobacter spp.
      among food-animals, but the rate in food-animals was significantly higher than in
      humans (84% vs. 56.7%, OR=4.0). Swine was significantly more likely to harbor
      erythromycin-resistant C. jejuni (14.8%) than chicken (3.5%, OR=4.9), cattle
      (1.8%, OR=9.3), or humans (3.0%, OR=5.7), and was associated with higher rates of
      erythromycin-resistant Campylobacter spp. (41.9%) than chicken (10.5%, OR=6.1)
      and humans (11.9%, OR=5.3). The high resistance rates to ciprofloxacin preclude
      the use of fluoroquinolones for treatment of campylobacteriosis in Mexico. Our
      results emphasize the need for ongoing and integrated surveillance of
      antimicrobial usage and antimicrobial susceptibility in humans and animals.

PMID- 22870939
TI  - Urovaginal fistula formation after gynaecological and obstetric surgical
      procedures: clinical experiences in a Scandinavian series.
AB  - OBJECTIVE: The aim of this retrospective study was to review what kinds of
      surgical procedures are most frequently complicated by urovaginal fistulae, to
      find out how they were diagnosed and managed, and to study the outcome after
      surgical reconstruction. MATERIAL AND METHODS: Nineteen women who underwent
      fistula repair at Sahlgrenska University Hospital between 2003 and 2009 were
      retrospectively studied by reviewing the medical records. RESULTS: For 17 of the
      19 patients hysterectomy was the causative procedure. Fourteen patients developed
      vesicovaginal and five developed ureterovaginal fistula. Urethrocystoscopy was
      sufficient for the diagnosis in nearly 50% of the patients and when combined with
      methylene blue instillation 90% of all fistulae were found. Several patients
      sought medical advice due to vaginal leakage following gynaecological surgery
      without the doctor suspecting a fistula, and for these patients the diagnosis was
      delayed. Eighteen patients were operated on with an abdominal approach and one
      with a vaginal approach, in all cases a minimum of 3 months after primary
      surgery. The reconstruction technique included the interposition of vascularized
      tissue. None of the patients reported leakage or relapse at follow-up after
      fistula repair. CONCLUSIONS: Hysterectomy was the most common cause behind the
      formation of urovaginal fistulae. Misinterpretation of symptoms after
      gynaecological surgery was common even in cases where the symptoms were
      indicative of a urovaginal fistula. Delayed fistula repair after a minimum of 3
      months, via the abdominal route and with the interposition of vascularized
      tissue, yielded an excellent final outcome.

PMID- 22870940
TI  - Comparison of methods to detect copy number alterations in cancer using simulated
      and real genotyping data.
AB  - BACKGROUND: The detection of genomic copy number alterations (CNA) in cancer
      based on SNP arrays requires methods that take into account tumour specific
      factors such as normal cell contamination and tumour heterogeneity. A number of
      tools have been recently developed but their performance needs yet to be
      thoroughly assessed. To this aim, a comprehensive model that integrates the
      factors of normal cell contamination and intra-tumour heterogeneity and that can
      be translated to synthetic data on which to perform benchmarks is indispensable.
      RESULTS: We propose such model and implement it in an R package called CnaGen to
      synthetically generate a wide range of alterations under different normal cell
      contamination levels. Six recently published methods for CNA and loss of
      heterozygosity (LOH) detection on tumour samples were assessed on this synthetic
      data and on a dilution series of a breast cancer cell-line: ASCAT, GAP, GenoCNA,
      GPHMM, MixHMM and OncoSNP. We report the recall rates in terms of normal cell
      contamination levels and alteration characteristics: length, copy number and LOH
      state, as well as the false discovery rate distribution for each copy number
      under different normal cell contamination levels.Assessed methods are in general
      better at detecting alterations with low copy number and under a little normal
      cell contamination levels. All methods except GPHMM, which failed to recognize
      the alteration pattern in the cell-line samples, provided similar results for the
      synthetic and cell-line sample sets. MixHMM and GenoCNA are the poorliest
      performing methods, while GAP generally performed better. This supports the
      viability of approaches other than the common hidden Markov model (HMM)-based.
      CONCLUSIONS: We devised and implemented a comprehensive model to generate data
      that simulate tumoural samples genotyped using SNP arrays. The validity of the
      model is supported by the similarity of the results obtained with synthetic and
      real data. Based on these results and on the software implementation of the
      methods, we recommend GAP for advanced users and GPHMM for a fully driven
      analysis.

PMID- 22870941
TI  - Effect of body posture on intraocular pressure and ocular perfusion pressure in
      nonglaucomatous pregnant women.
AB  - PURPOSE: To investigate the effect of different positions on the intraocular
      pressure (IOP) and ocular perfusion pressure (OPP) in nonglaucomatous pregnant.
      MATERIAL AND METHODS: Thirty-one women in their third trimester of pregnancy were
      enrolled in this prospective and observational study. IOP in both eyes was
      measured with a Tono-pen(r) in the sitting position (Si-P), in the supine
      position (Su-P), in the right lateral decubitus position (R-LDP), and left
      lateral decubitus position (L-LDP). Systolic and diastolic blood pressure (sBP
      and dBP) were measured with a digital automatic blood pressure monitor at after
      10 min in each position. Mean blood pressure ([mBP] = dBP + 1/3 [sBP-dBP]) and
      mean OPP (OPP = 2/3 mBP-IOP) were also calculated. Three IOP measurements were
      performed by the same clinician at the 15th min in each position. RESULTS: The
      mean IOP was 13.6 +/- 3.4 mmHg in Si-P; 16.7 +/- 3.5 mmHg in Su-P; 16.4 +/- 3.5
      mmHg in the R-LDP, and 16.6 +/- 3.7 mmHg in the L-LDP. IOP was significantly
      lower in Si-P compared to Su-P, R-LDP, or L-LDP. The mean OPP was 46.41 +/- 5.54
      in Si-P; 39.71 +/- 6.96 in Su-P; 36.81 +/- 6.57 in the R-LDP; and 33.53 +/- 7.63
      in the L-LDP. OPP values were significantly different between each body position
      when multiple comparisons were performed. CONCLUSION: According to our data we
      conclude that Si-P yields the lowest IOP and the highest OPP compared with Su-P,
      R-LDP, and L-LDP in healthy pregnant women.

PMID- 22870942
TI  - A phase plane graph based model of the ovulatory cycle lacking the "positive
      feedback" phenomenon.
AB  - When hormones during the ovulatory cycle are shown in phase plane graphs,
      reported FSH and estrogen values form a specific pattern that resembles the
      leaning "&" symbol, while LH and progesterone (Pg) values form a "boomerang"
      shape. Graphs in this paper were made using data reported by Stricker et al.
      [Clin Chem Lab Med 2006;44:883-887]. These patterns were used to construct a
      simplistic model of the ovulatory cycle without the conventional "positive
      feedback" phenomenon. The model is based on few well-established
      relations:hypothalamic GnRH secretion is increased under estrogen exposure during
      two weeks that start before the ovulatory surge and lasts till lutheolysis.the
      pituitary GnRH receptors are so prone to downregulation through ligand binding
      that this must be important for their function.in several estrogen target tissue
      progesterone receptor (PgR) expression depends on previous estrogen binding to
      functional estrogen receptors (ER), while Pg binding to the expressed PgRs
      reduces both ER and PgR expression.Some key features of the presented model are
      here listed:High GnRH secretion induced by the recovered estrogen exposure starts
      in the late follicular phase and lasts till lutheolysis. The LH and FSH surges
      start due to combination of accumulated pituitary GnRH receptors and increased
      GnRH secretion. The surges quickly end due to partial downregulation of the
      pituitary GnRH receptors (64% reduction of the follicular phase pituitary GnRH
      receptors is needed to explain the reported LH drop after the surge). A strong
      increase in the lutheal Pg blood level, despite modest decline in LH levels, is
      explained as delayed expression of pituitary PgRs. Postponed pituitary PgRs
      expression enforces a negative feedback loop between Pg levels and LH secretions
      not before the mid lutheal phase.Lutheolysis is explained as a consequence of Pg
      binding to hypothalamic and pituitary PgRs that reduces local ER expression. When
      hypothalamic sensitivity to estrogen is diminished due to lack of local ERs,
      hypothalamus switches back to the low GnRH secretion rate, leading to low
      secretion of gonadotropins and to lutheolysis. During low GnRH secretion rates,
      previously downregulated pituitary GnRH receptors recover to normal levels and
      thus allow the next cycle.Possible implications of the presented model on several
      topics related to reproductive physiology are shortly discussed with some
      evolutionary aspects including the emergence of menopause.

PMID- 22870943
TI  - Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide
      immunization is associated with differential responses in separate compartments
      of the choroid plexus.
AB  - BACKGROUND: There is increasing awareness that, aside from producing
      cerebrospinal fluid, the choroid plexus (CP) might be a key regulator of immune
      activity in the central nervous system (CNS) during neuroinflammation.
      Specifically, the CP has recently been posited to control entry of sentinel T
      cells into the uninflamed CNS during the early stages of neuroinflammatory
      diseases, like multiple sclerosis (MS) and its animal model experimental
      autoimmune encephalomyelitis (EAE). As the CP is compartmentalized into a stromal
      core containing fenestrated capillaries devoid of typical blood-brain barrier
      properties, surrounded by a tight junction-expressing choroidal epithelium, each
      of these compartments might mount unique responses that instigate the
      neuroinflammatory process. METHODS: To discern responses of the respective CP
      stromal capillary and choroidal epithelial tissues during evolving
      neuroinflammation, we investigated morphology and in situ expression of 93 immune
      related genes during early stages of EAE induced by immunization with myelin
      oligodendrocyte glycoprotein peptide (MOG35-55). Specifically, 3-D
      immunofluorescent imaging was employed to gauge morphological changes, and laser
      capture microdissection was coupled to an Immune Panel TaqMan Low Density Array
      to detail alterations in gene expression patterns at these separate CP sites on
      days 9 and 15 post-immunization (p.i.). To resolve CP effects due to autoimmunity
      against MOG peptide, from those due to complete Freund's adjuvant (CFA) and
      pertussis toxin (PTX) included in the immunization, analysis was performed on MOG
      CFA/PTX-treated, CFA/PTX-treated, and naive cohorts. RESULTS: The CP became
      swollen and displayed significant molecular changes in response to MOG-CFA/PTX
      immunization. Both stromal capillary and choroidal epithelial tissues mounted
      vigorous, yet different, changes in expression of numerous genes over the time
      course analyzed - including those encoding adhesion molecules, cytokines,
      chemokines, statins, interleukins, T cell activation markers, costimulatory
      molecules, cyclooxygenase, pro-inflammatory transcription factors and pro
      apoptotic markers. Moreover, CFA/PTX-treatment, alone, resulted in extensive,
      though less robust, alterations in both CP compartments. CONCLUSIONS: MOG-CFA/PTX
      immunization significantly affects CP morphology and stimulates distinct
      expression patterns of immune-related genes in CP stromal capillary and
      epithelial tissues during evolving EAE. CFA/PTX treatment, alone, causes
      widespread gene alterations that could prime the CP to unlock the CNS to T cell
      infiltration during neuroinflammatory disease.

PMID- 22870944
TI  - Stool submission by general practitioners in SW England - when, why and how? A
      qualitative study.
AB  - BACKGROUND: We know little about when and why general practitioners (GPs) submit
      stool specimens in patients with diarrhoea. The recent UK-wide intestinal
      infectious disease (IID2) study found ten GP consultations for every case
      reported to national surveillance. We aimed to explore what factors influence
      GP's decisions to send stool specimens for laboratory investigation, and what
      guidance, if any, informs them. METHODS: We used qualitative methods that enabled
      us to explore opinions and ask open questions through 20 telephone interviews
      with GPs with a range of stool submission rates in England, and a discussion
      group with 24 GPs. Interviews were transcribed and subjected to content analysis.
      RESULTS: Interviews: GPs only sent stool specimens to microbiology if diarrhoea
      persisted for over one week, after recent travel, or the patient was very unwell.
      Very few had a systematic approach to determine the clinical or public health
      need for a stool specimen. Only two GPs specifically asked patients about blood
      in their stool; only half asked about recent antibiotics, or potential food
      poisoning, and few asked about patients' occupations. Few GPs gave patients
      advice on how to collect specimens.Results from interviews and discussion group
      in relation to guidance: All reported that the HPA stool guidance and patient
      collection instructions would be useful in their clinical work, but only one GP
      (an interviewee) had previously accessed them. The majority of GPs would value
      links to guidance on electronic requests. Most GPs were surprised that a negative
      stool report did not exclude all the common causes of IID. CONCLUSIONS: GPs value
      stool culture and laboratories should continue to provide it. Patient
      instructions on how to collect stool specimens should be within stool collection
      kits. Through readily accessible guidance and education, GPs need to be
      encouraged to develop a more systematic approach to eliciting and recording
      details in the patient's history that indicate greater risk of severe infection
      or public health consequences. Mild or short duration IID (under one week) due to
      any cause is less likely to be picked up in national surveillance as GPs do not
      routinely submit specimens in these cases.

PMID- 22870945
TI  - Legionella on board trains: effectiveness of environmental surveillance and
      decontamination.
AB  - BACKGROUND: Legionella pneumophila is increasingly recognised as a significant
      cause of sporadic and epidemic community-acquired and nosocomial pneumonia. Many
      studies describe the frequency and severity of Legionella spp. contamination in
      spa pools, natural pools, hotels and ships, but there is no study analysing the
      environmental monitoring of Legionella on board trains. The aims of the present
      study were to conduct periodic and precise environmental surveillance of
      Legionella spp. in water systems and water tanks that supply the toilet systems
      on trains, to assess the degree of contamination of such structures and to
      determine the effectiveness of decontamination. METHODS: A comparative pre-post
      ecological study was conducted from September 2006 to January 2011. A total of
      1,245 water samples were collected from plumbing and toilet water tanks on
      passenger trains. The prevalence proportion of all positive samples was
      calculated. The unpaired t-test was performed to evaluate statistically
      significant differences between the mean load values before and after the
      decontamination procedures; statistical significance was set at p <= 0.05.
      RESULTS: In the pre-decontamination period, 58% of the water samples were
      positive for Legionella. Only Legionella pneumophila was identified: 55.84% were
      serogroup 1, 19.03% were serogroups 2-14 and 25.13% contained both serogroups.
      The mean bacterial load value was 2.14 * 10(3) CFU/L. During the post
      decontamination period, 42.75% of water samples were positive for Legionella
      spp.; 98.76% were positive for Legionella pneumophila: 74.06% contained serogroup
      1, 16.32% contained serogroups 2-14 and 9.62% contained both. The mean bacterial
      load in the post-decontamination period was 1.72 * 10(3) CFU/L. According to the
      t-test, there was a statistically significant decrease in total bacterial load
      until approximately one and a half year after beginning the decontamination
      programme (p = 0.0097). CONCLUSIONS: This study indicates that systematic
      environmental surveillance could be a useful approach for assessing the risk of
      exposure to Legionella bacteria, which still represents a public health threat.
      According to the study results, an environmental surveillance programme, followed
      by decontamination procedures where necessary, would decrease the total bacterial
      count, protecting the health of travellers and workers.

PMID- 22870946
TI  - Mechanism of flexibility control for ATP access of hepatitis C virus NS3
      helicase.
AB  - Hepatitis C virus (HCV) NS3 helicase couples adenosine triphosphate (ATP) binding
      and hydrolysis to polynucleotide unwinding. Understanding the regulation
      mechanism of ATP binding will facilitate targeting of the ATP-binding site for
      potential therapeutic development for hepatitis C. T324, an amino acid residue
      connecting domains 1 and 2 of NS3 helicase, has been suggested as part of a
      flexible hinge for opening of the ATP-binding cleft, although the detailed
      mechanism remains largely unclear. We used computational simulation to examine
      the mutational effect of T324 on the dynamics of the ATP-binding site. A mutant
      model, T324A, of the NS3 helicase apo structure was created and energy was
      minimized. Molecular dynamics simulation was conducted for both wild type and the
      T324A mutant apo structures to compare their differences. For the mutant
      structure, histogram analysis of pairwise distances between residues in domains 1
      and 2 (E291-Q460, K210-R464 and R467-T212) showed that separation between the two
      domains was reduced by ~10% and the standard deviation by ~33%. Root mean square
      fluctuation (RMSF) analysis demonstrated that residues in close proximity to
      residue 324 have at least 30% RMSF value reductions in the mutant structure.
      Solvent RMSF analysis showed that more water molecules were trapped near D290 and
      H293 in domain 1 to form an extensive interaction network constraining cleft
      opening. We also demonstrated that the T324A mutation established a new atomic
      interaction with V331, revealing that an atomic interaction cascade from T324 to
      residues in domains 1 and 2 controls the flexibility of the ATP-binding cleft.

PMID- 22870947
TI  - Is there an increased risk of complications with laparoscopy looking for a
      contralateral patent processus vaginalis?
AB  - BACKGROUND: In young children with a unilateral congenital inguinal hernia, the
      relatively high incidence of an occult contralateral patent processus vaginalis
      (CPPV) has led to the practice of laparoscopic contralateral exploration. The
      effect on postoperative complications such as surgical site infection from
      performing the laparoscopy has not been previously reported. PATIENTS AND
      METHODS: A retrospective review was conducted on all patients who underwent a
      unilateral inguinal hernia repair from January 1, 2000 to March 1, 2010. We
      compared those children who underwent laparoscopic evaluation of the
      contralateral inguinal ring with those who did not. Patient demographics and
      operative data outcomes were evaluated. Student's t test was used to compare
      continuous variables, and the chi-squared test with Yates's correction was used
      for discrete variables. RESULTS: There were 1164 patients who underwent a
      unilateral inguinal hernia repair during the 10-year study period, and
      laparoscopy was used in 1010 patients. There were no intraoperative complications
      from the laparoscopy. In the group who underwent laparoscopy, the mean age was
      4.0+/-3.6 years old, and 88% were male. At laparoscopic exploration, 315 (31%)
      patients were found to have a CPPV. There were 10 patients (1.0%) who developed a
      surgical site infection. Infection developed in the side used for laparoscopic
      exploration in 9 patients and in the contralateral side in 1 patient. All
      patients with surgical site infections were treated initially with oral
      antibiotics. Abscesses developed in 2 patients, requiring incision and drainage.
      No patient required hospital admission or reoperation. In the 154 patients who
      did not undergo laparoscopy, mean age was 4.3+/-4.4 years (P=.35), and 85.8% were
      male (P=.54). There was one wound infection identified in this control group
      (0.6%) (P=1.00). There was no difference in rate of recurrence (control group,
      0%; exploration group, 0.6%; P=.72). CONCLUSIONS: There is minimal risk of
      infection or recurrence following unilateral inguinal hernia repair, and this
      risk is not increased with the use of contralateral exploration using
      laparoscopy.

PMID- 22870948
TI  - Ring expansion of spiro-thiolactam in rhodamine scaffold: switching the
      recognition preference by adding one atom.
AB  - A new rhodamine spiro scaffold with a six-membered reactive ring was developed by
      inserting a nitrogen atom in the known probe rhodamine B spiro thiohydrazide,
      which switched the recognition preference of the probe from Hg(2+) to Cu(2+).
      This probe is shown to be an efficient "turn-on" fluorescent chemodosimeter for
      Cu(2+) in a neutral aqueous medium. Mechanism studies suggested that the probe
      opened its spiro-ring by a Cu(2+)-induced transformation of the cyclic
      thiosemicarbazide moiety to an isothiocyanate group.

PMID- 22870950
TI  - The suicide assessment scale: psychometric properties of a Norwegian language
      version.
AB  - BACKGROUND: Rating scales are valuable tools in suicide research and can also be
      useful supplements to the clinical interview in suicide risk assessments. This
      study describes the psychometric properties of a Norwegian language version of
      the Suicide Assessment Scale Self-report version (SUAS-S). METHODS: Participants
      were fifty-two patients (mean age = 39.3 years, SD = 10.7) with major depression
      (53.8%), bipolar disorder (25.0%) and/or a personality disorder (63.5%) referred
      to a psychiatric outpatient clinic. The SUAS-S, the screening section of the Beck
      Scale for Suicidal Ideation (BSS-5), the Beck Depression Inventory (BDI), Beck's
      Hopelessness Scale (BHS), the Symptom Check-List-90 R (SCL-90R) and the Clinical
      Global Impression for Severity of Suicidality (CGI-SS) were administered. One
      week later, the patients completed the SUAS-S a second time. RESULTS: Cronbach's
      alpha for SUAS-S was 0.88 and the test-retest reliability was 0.95 (95% CI: 0.93-
      0.97). SUAS-S was positively correlated with the BSS-5 (r = 0.66; 95% CI: 0.47
      0.85) for the study sample as a whole and for the suicidal (r = 0.52) and non
      suicidal groups (r = 0.50) respectively. There was no difference between the SUAS
      S and the BSS-5 in the ability to identify suicidality. This ability was more
      pronounced when the suicide risk was high. There was a substantial
      intercorrelation between the score on the SUAS-S and the BDI (0.81) and the BHS
      (0.76). The sensitivity and specificity of the SUAS-S was explored and an
      appropriate clinical cut-off value was assessed. CONCLUSIONS: The study revealed
      good internal consistency, test-retest reliability and concurrent validity for
      the Suicide Assessment Scale Self-report version. The discriminatory ability for
      suicidality was comparable to that of the BSS-5.

PMID- 22870949
TI  - Hypothyroidism in the adult rat causes incremental changes in brain-derived
      neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration
      of postsynaptic density.
AB  - BACKGROUND: Adult hypothyroidism is a highly prevalent condition that impairs
      processes, such as learning and memory. Even though tetra-iodothyronine (T(4))
      treatment can overcome the hypothyroidism in the majority of cases, it cannot
      fully recover the patient's learning capacity and memory. In this work, we
      analyzed the cellular and molecular changes in the adult brain occurring with the
      development of experimental hypothyroidism. METHODS: Adult male Sprague-Dawley
      rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce
      hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus
      of control and hypothyroid adult rats by confocal microscopy. The content of
      brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked
      immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse
      and the postsynaptic density (PSD) were analyzed by electron microscopy. The
      content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl
      D-aspartate receptor (NMDAr) were analyzed by immunoblot. RESULTS: We observed
      that the hippocampus of hypothyroid adult rats displayed increased apoptosis
      levels in neurons and astrocyte and reactive gliosis compared with controls.
      Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of
      hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at
      the PSD of the CA3 region of hypothyroid rats, compared with controls. We also
      observed that the glutamatergic synapses from the stratum radiatum of CA3 from
      hypothyroid rats, contained thinner PSDs than control rats. This observation was
      in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid
      animals. CONCLUSIONS: Our data suggest that adult hypothyroidism affects the
      hippocampus by a mechanism that alters the composition of PSD, reduces neuronal
      and astrocyte survival, and alters the content of the signaling neurotrophic
      factors, such as BDNF.

PMID- 22870951
TI  - Ginkgo biloba extract and bilberry anthocyanins improve visual function in
      patients with normal tension glaucoma.
AB  - Ginkgo biloba extract (GBE) and anthocyanins are considered beneficial for
      various vascular diseases. This study was performed to evaluate the effect of GBE
      and anthocyanins on visual function in patients with normal tension glaucoma
      (NTG) based on the vascular theory of mechanisms of glaucomatous optic nerve
      damage. Retrospective analysis was carried out by a chart review of 332 subjects
      (209 men and 123 women) who were treated with anthocyanins (n=132), GBE (n=103),
      or no medication (control, n=97). Humphrey Visual Field (HVF) test, logarithm of
      the minimal angle of resolution best-corrected visual acuity (logMAR BCVA),
      intraocular pressure, blood pressure, and fasting blood glucose were determined
      before and after treatment. Complete ocular and systemic examinations were
      performed. The mean follow-up duration was 23.82+/-9.84 (range, 12-59) months;
      the mean anthocyanin treatment duration was 24.32+/-10.43 (range, 6-53) months,
      and the mean GBE treatment duration was 23.81+/-10.36 months (range, 6-59)
      months. After anthocyanin treatment, the mean BCVA for all eyes improved from
      0.16 (+/-0.34) to 0.11 (+/-0.18) logMAR units (P=.008), and HVF mean deviation
      improved from -6.44 (+/-7.05) to -5.34 (+/-6.42) (P=.001). After GBE treatment,
      HVF mean deviation improved from -5.25 (+/-6.13) to -4.31 (+/-5.60) (P=.002). A
      generalized linear model demonstrated that the final BCVA was not affected by
      demographic differences among the groups. These results suggest that anthocyanins
      and GBE may be helpful in improving visual function in some individuals with NTG.

PMID- 22870952
TI  - How do persons with dementia participate in decision making related to health and
      daily care? a multi-case study.
AB  - BACKGROUND: Many countries have passed laws giving patients the right to
      participate in decisions about health care. People with dementia cannot be
      assumed to be incapable of making decisions on their diagnosis alone as they may
      have retained cognitive abilities.The purpose of this study was to gain a better
      understanding of how persons with dementia participated in making decisions about
      health care and how their family carers and professional caregivers influenced
      decision making. METHODS: This Norwegian study had a qualitative multi-case
      design. The triad in each of the ten cases consisted of the person with dementia,
      the family carer and the professional caregiver, in all 30 participants.
      Inclusion criteria for the persons with dementia were: (1) 67 years or older (2)
      diagnosed with dementia (3) Clinical Dementia Rating score 2, moderate dementia;
      (3) able to communicate verbally. The family carers and professional caregivers
      were then asked to participate.A semi-structured interview guide was used in
      interviews with family carers and professional caregivers. Field notes were
      written after participant observation of interactions between persons with
      dementia and professional caregivers during morning care or activities at a day
      centre. How the professional caregivers facilitated decision making was the focus
      of the observations that varied in length from 30 to 90 minutes. The data were
      analyzed using framework analysis combined with a hermeneutical interpretive
      approach. RESULTS: Professional caregivers based their assessment of mental
      competence on experience and not on standardized tests. Persons with dementia
      demonstrated variability in how they participated in decision making. Pseudo
      autonomous decision making and delegating decision making were new categories
      that emerged. Autonomous decision making did occur but shared decision making was
      the most typical pattern. Reduced mental capacity, lack of available choices or
      not being given the opportunity to participate led to non-involvement. Not all
      decisions were based on logic; personal values and relationships were also
      considered. CONCLUSIONS: Persons with moderate dementia demonstrated variability
      in how they participated in decision making. Optimal involvement was facilitated
      by positioning them as capable of influencing decisions, assessing decision
      specific competence, clarifying values and understanding the significance of
      relationships and context.

PMID- 22870953
TI  - Disulfide bond formation in the cytoplasm.
AB  - SIGNIFICANCE: Disulfide bond formation is critical for biogenesis of many
      proteins. While most studies in this field are aimed at elucidating the
      mechanisms in the endoplasmic reticulum, intermembrane space of mitochondria, and
      prokaryotic periplasm, structural disulfide bond formation also occurs in other
      compartments including the cytoplasm. Such disulfide bond formation is essential
      for biogenesis of some viruses, correct epidermis biosynthesis, thermal
      adaptation of some extremophiles, and efficient recombinant protein production.
      RECENT ADVANCES: The majority of work in this new field has been reported in the
      past decade. Within the past few years very significant new data have emerged on
      the catalytic and noncatalytic mechanisms for disulfide bond formation in the
      cytoplasm. This includes the crystal structure of a key component of viral
      oxidative protein folding, identification of a missing component in cytoplasmic
      disulfide bond formation in hyperthermophiles, and introduction of de novo
      dithiol oxidants in engineered oxidative folding pathways. CRITICAL ISSUES AND
      FUTURE DIRECTIONS: While a broad picture of cytoplasmic disulfide bond formation
      has emerged many critical questions remain unanswered. The individual components
      in the natural systems are largely known, but the molecular mechanisms by which
      these processes occur are largely deduced from the mechanisms of analogous
      components in other compartments. This prevents full understanding and
      manipulation of these systems, including the potential for novel anti-viral drugs
      based on the unique features of their sulfhydryl oxidases and the generation of
      more efficient cell factories for the large-scale production of therapeutic and
      industrial proteins.

PMID- 22870955
TI  - Observation of negative and positive trions in the electrochemically carrier
      doped single-walled carbon nanotubes.
AB  - Understanding of electronic and optical features of single-walled carbon
      nanotubes (SWNTs) has been a central issue in science and nanotechnology of
      carbon nanotubes. We describe the detection of both the positive trion
      (positively charged exciton) and negative trion (negatively charged exciton) as a
      three-particle bound state in the SWNTs at room temperature by an in situ
      photoluminescence spectroelectrochemistry method for an isolated SWNT film cast
      on an ITO electrode. The electrochemical hole and electron dopings enable us to
      detect such trions on the SWNTs. The large energy difference between the singlet
      bright exciton and the negative and positive trions showing a tube diameter
      dependence is determined by both the exchange splitting energy and the trion
      binding energy. In contrast to conventional compound semiconductors, on the
      SWNTs, the negative trion has almost the same binding energy to the positive
      trion, which is attributed to nearly identical effective masses of the holes and
      electrons.

PMID- 22870954
TI  - Ligand affinity and kinase activity are independent of bacterial chemotaxis
      receptor concentration: insight into signaling mechanisms.
AB  - Binding of attractant to bacterial chemotaxis receptors initiates a transmembrane
      signal that inhibits the kinase CheA bound ~300 A distant at the other end of the
      receptor. Chemoreceptors form large clusters in many bacterial species, and the
      extent of clustering has been reported to vary with signaling state. To test
      whether ligand binding regulates kinase activity by modulating a clustering
      equilibrium, we measured the effects of two-dimensional receptor concentration on
      kinase activity in proteoliposomes containing the purified Escherichia coli
      serine receptor reconstituted into vesicles over a range of lipid:protein molar
      ratios. The IC(50) of kinase inhibition was unchanged despite a 10-fold change in
      receptor concentration. Such a change in concentration would have produced a
      measurable shift in the IC(50) if receptor clustering were involved in kinase
      regulation, based on a simple model in which the receptor oligomerization and
      ligand binding equilibria are coupled. These results indicate that the primary
      signal, ligand control of kinase activity, does not involve a change in receptor
      oligomerization state. In combination with previous work on cytoplasmic fragments
      assembled on vesicle surfaces [Besschetnova, T. Y., et al. (2008) Proc. Natl.
      Acad. Sci. U.S.A.105, 12289-12294], this suggests that binding of ligand to
      chemotaxis receptors inhibits the kinase by inducing a conformational change that
      expands the membrane area occupied by the receptor cytoplasmic domain, without
      changing the number of associated receptors in the signaling complex.

PMID- 22870956
TI  - The semantics of Chemical Markup Language (CML) for computational chemistry :
      CompChem.
AB  - : This paper introduces a subdomain chemistry format for storing computational
      chemistry data called CompChem. It has been developed based on the design,
      concepts and methodologies of Chemical Markup Language (CML) by adding
      computational chemistry semantics on top of the CML Schema. The format allows a
      wide range of ab initio quantum chemistry calculations of individual molecules to
      be stored. These calculations include, for example, single point energy
      calculation, molecular geometry optimization, and vibrational frequency analysis.
      The paper also describes the supporting infrastructure, such as processing
      software, dictionaries, validation tools and database repositories. In addition,
      some of the challenges and difficulties in developing common computational
      chemistry dictionaries are discussed. The uses of CompChem are illustrated by two
      practical applications.

PMID- 22870957
TI  - Stereoselective synthesis of unsaturated and functionalized L-NHBoc amino acids,
      using Wittig reaction under mild phase-transfer conditions.
AB  - The stereoselective synthesis of a new amino acid phosphonium salt was described
      by quaternization of melting triphenylphosphine with the gamma-iodo NHBoc-amino
      ester, derived from L-aspartic acid. The deprotection of the carboxylic acid
      function to afford the phosphonium salt with a free carboxylic acid group was
      achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt
      was used in the Wittig reaction with aromatic or aliphatic aldehydes and
      trifluoroacetophenone, under solid-liquid phase-transfer conditions in
      chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the
      corresponding unsaturated amino acids without racemization. Thus, the reaction
      with substituted aldehydes allows to graft various functionalized groups on the
      lateral chain of the amino acid, such as trifluoromethyl, cyano, nitro,
      ferrocenyl, boronato, or azido. In addition, the reaction of the amino acid
      Wittig reagent with alpha,beta-unsaturated aldehydes leads to amino acids bearing
      a diene on the lateral chain. Finally, this amino acid phosphonium salt appears
      to be a new powerful tool for the preparation of unsaturated and non
      proteinogenic alpha-amino acids, directly usable for the synthesis of customized
      peptides.

PMID- 22870958
TI  - Effect of cyclosporine A on hepatic carbohydrate metabolism and hepatic gene
      expression in rat.
AB  - OBJECTIVE: Cyclosporine A (CsA)-based therapy has been implicated in the
      development of diabetes. Hence, its effects on hepatic carbohydrate metabolism
      and gene expression will be investigated. METHODS: Sprague-Dawley rats given 15
      mg/kg body weight/day of CsA for 20 days, as well as healthy untreated animals,
      received a glucose load enriched with [U-(13)C]glucose and deuterated water to
      resolve load and endogenous contributions to plasma glucose. Blood glucose and
      plasma insulin levels were assayed and at 60-min post-load, plasma glucose (13)C
      and (2)H-enrichments were analyzed by nuclear magnetic resonance spectroscopy and
      liver tissue analyzed for hepatic gene expression. RESULTS: CsA-treated rats were
      glucose intolerant relative to controls (AUC(glucose) = 21,297 +/- 857 versus
      14,183 +/- 1094, p < 0.01). Contributions from endogenous glucose production
      (EGP) were significantly elevated in CsA-treated rats (179 +/- 16 versus 123 +/-
      13 mg/dl, p < 0.05). The increased endogenous contributions were attributable to
      glycogenolysis or glucose-G6P cycling and not to gluconeogenesis. Significantly
      higher expressions of fatty acid synthase and acetyl-CoA carboxylase 1 and 2
      genes were observed in CsA-treated rats. CONCLUSIONS: CsA-altered glucose
      metabolism and gene expression could reflect increased hepatic insulin
      resistance. In the liver of CsA-treated animals, EGP suppression is impaired
      whereas hepatic de novo lipogenesis is enhanced contributing to dysregulated
      glucose and lipid metabolism.

PMID- 22870959
TI  - Assessment of relationship between fungal aerosol within a municipal dump and
      epiphytic mycoflora of crop plants.
AB  - A field study was performed to assess whether fungal aerosol of a municipal dump
      may impact on quantitative and qualitative characteristics of epiphytic mycoflora
      of crop plants cultivated in vicinity of the dump. Sampling sites were located at
      every side of the dump. Plant samples were collected from field bean, spring
      wheat and potato. The highest concentration of fungal aerosol was found at the
      field located south of the dump within the zone of 250 m next to its borders. For
      this zone, the most numerous and diverse mycoflora was ascertained, and the
      plants cultivated were the most damaged. The results suggest that the municipal
      dump was not the source of phytopathogenic fungi; however, different emissions of
      contaminants from the dump might cause a decline in the intrinsic plant
      resistance against the pathogens.

PMID- 22870960
TI  - Therapeutic effects of low-level laser therapy after premolar extraction in
      adolescents: a randomized double-blind clinical trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of low-level
      laser therapy (LLLT) on wound healing process and pain levels after premolar
      extraction in adolescents. BACKGROUND DATA: The advantage of using LLLT in oral
      surgeries is the reduction of inflammation and postoperative discomfort; however,
      the optimal dosing parameters and treatment effects in surgical procedures are
      inconclusive. METHODS: A double-blind, randomized, controlled clinical trial was
      conducted with 14 patients who were to undergo surgical removal of premolars.
      Patients were randomly allocated to the LLLT (test) group and placebo (control)
      group. Patients in the test group received 5.1 J (60 J/cm(2)) of energy density
      of a gallium-aluminum-arsenide (GaAlAs) diode laser (wavelength, 830 nm; output
      power, 0.1 W) at three different points intraorally, 1 cm from the target tissue
      immediately and at 48 and 72 h after the surgical procedure. For patients in the
      placebo group, the laser device was applied to the same points without activating
      the hand piece. The wound healing process was evaluated by an independent
      examiner by visual inspection with the support of digital photographs at baseline
      and 2, 7, and 15 days postoperatively. Patients recorded the degree of pain using
      the visual analogue scale (VAS). RESULTS: Compared with the placebo group, the
      test group showed a lower intensity of pain, but this difference was not
      statistically significant at any time point. The wound healing process was
      similar in both groups. CONCLUSIONS: Within the limitations of this study, the
      LLLT parameters used neither increased the wound healing process nor
      significantly decreased pain intensity after premolar extraction in adolescents.

PMID- 22870961
TI  - James William Osborne.

PMID- 22870962
TI  - Repair of potentially lethal damage in X-irradiated HeLa cells. 1966.

PMID- 22870963
TI  - Cyclic X-ray responses in mammalian cells in vitro. 1968.
AB  - Various radiation responses in mammalian cells depend on the position of the cell
      within its generation cycle (that is, its age) at the time of irradiation.
      Studies have most often been made by irradiating synchronized populations of
      cells in vitro. Results in different cell lines are not easy to compare, but an
      attempt has been made here to point out similarities and differences with regard
      to cell killing and division delay. In general, survival data obtained so far
      show that, in cells with a short G(1), cells are most sensitive in mitosis and in
      G(2), less sensitive in G(1), and least sensitive during the latter part of the S
      period. In cells with a long G(1), in addition to the above, there is usually a
      resistant phase early in G(1) followed by a sensitive stage near its end. (The
      latter may be as sensitive as mitosis.) Exceptions to the above, especially in
      some L cell sublines, have been noted, and a possible explanation is given.   In
      Chinese hamster cells, maximum survival after irradiation occurs during S, but it
      does not coincide with the time of the maximum rate of DNA synthesis or with the
      time of the maximum number of cells in DNA synthesis, and changes in survival
      also occur in cells inhibited from synthesizing DNA. Rather, survival depends on
      the position the cell has reached in the cycle at that time, which involves not
      only DNA synthesis but other processes as well. Survival is not completely
      correlated with DNA synthesis, since halting DNA synthesis just before or just
      after irradiation only slightly affects survival at its maximum.   Division delay
      exhibits a pattern of response which is similar in most cell lines. Delay is
      considerable for cells irradiated in mitosis, is small for cells in G(1),
      increases to a maximum for cells during S, and declines for cells in G(2). L
      cells or human kidney cells may have a longer delay for cells irradiated in G(2)
      than for those irradiated in S. The results can be explained in terms of a two
      component model of division delay. One component results from the prolongation of
      the S period due to the reduced rate of DNA synthesis, and the other, a block in
      G(2), is independent of DNA synthesis. The proportion of the two components may
      vary in different cell lines.

PMID- 22870964
TI  - The effect of multiple small doses of X rays on skin reactions in the mouse and a
      basic interpretation. 1976.
AB  - Multiple-fraction experiments have been carried out to determine the response to
      repeated small doses of 240 kV X rays down to 45 rad per fraction, using the
      mouse skin reaction system. A method of irradiating without anesthetic was
      developed so that up to 64 fractions could be given within 8 days; over this
      time, proliferation was negligible. It was found that the total dose required to
      produce a given reaction continued to rise with the number of fractions above 30
      fractions, in contradiction to the recent conclusions of Dutreix and colleagues.
      The plot of reciprocal total dose against size of each fraction was shown to be
      linear. This finding led to an analysis in terms of a function F(e), which is
      proportional to the slope of the chord of the appropriate cell survival curve
      from the origin to the dose per fraction used. The cell survival curve derived
      here was well fitted by an equation of the form (s = e(-(alphaD+betaD(2)). The
      initial slope was 1/690 rad and the slope at 2340 rad was 1/126 rad. Thus, 1 rad
      at a dose approaching 0 rad has 18% of the effect of 1 rad at a single dose of
      2340 rad for mouse skin reactions. A cell survival theory based on Neary's theory
      of chromosome aberrations is presented and the current results are consistent
      with the postulate that cell death results from the formation of chromosome
      aberrations.

PMID- 22870965
TI  - Thermally enhanced radioresponse of cultured Chinese hamster cells: inhibition of
      repair of sublethal damage and enhancement of lethal damage. 1974.

PMID- 22870966
TI  - Studies of mortality of atomic bomb survivors. Report 13: solid cancer and
      noncancer disease mortality: 1950-1997. 2003.

PMID- 22870967
TI  - The nature of intestinal radiation death. 1956.

PMID- 22870968
TI  - Electron-affinic sensitization VII. A correlation between structures, one
      electron reduction potentials, and efficiencies of nitroimidazoles as hypoxic
      cell radiosensitizers. 1976.

PMID- 22870969
TI  - The rate of strand separation in alkali of DNA of irradiated mammalian cells.
      1975.

PMID- 22870970
TI  - Modification of cell lethality at elevated temperatures the pH effect 1977.

PMID- 22870971
TI  - A generalized formulation of dual radiation action.

PMID- 22870972
TI  - Chemical radioprotection and radiosensitization of Mammalian cells growing in
      vitro. 1973.

PMID- 22870973
TI  - Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation
      induced genomic instability and bystander effects in vitro. 2003.

PMID- 22870974
TI  - Mean inactivation dose: a useful concept for intercomparison of human cell
      survival curves. 1984.

PMID- 22870976
TI  - Energy transfer mechanisms and the molecular exciton model for molecular
      aggregates(1, 2). 1963.

PMID- 22870977
TI  - A direct measurement of the radiation sensitivity of normal mouse bone marrow
      cells. 1961.

PMID- 22870978
TI  - Heterogeneity in radiation-induced DNA damage and repair in tumor and normal
      cells measured using the "comet" assay. 1990.

PMID- 22870979
TI  - Thyroid cancer after exposure to external radiation: a pooled analysis of seven
      studies. 1995.

PMID- 22870980
TI  - Studies of the mortality of atomic bomb survivors. report 12, part I. Cancer:
      1950-1990. 1996.

PMID- 22870981
TI  - Radiation response of mammalian cells grown in culture I. Repair of X-ray damage
      in surviving Chinese hamster cells. 1960.

PMID- 22870982
TI  - X-ray sensitivity during the cell generation cycle of cultured Chinese hamster
      cells. 1966.

PMID- 22870984
TI  - Facile preparation of cationic gold nanoparticle-bioconjugates for cell
      penetration and nuclear targeting.
AB  - The present work faces the rising demand of cationic particles of different sizes
      for biological applications, especially in gene therapies and nanotoxicology
      studies. A simple phase-transfer methodology has been developed for the
      functionalization of gold nanoparticles (Au NPs) with a variety of ligands, both
      cationic and anionic in aqueous solution, employing different nanocrystal sizes
      with narrow size distributions. Successful functionalization has been
      demonstrated by UV-vis spectroscopy, DLS, zeta-potential, and FTIR spectroscopy
      characterization of the particles before and after the phase transfer. The
      intracellular uptake of the differently charged Au NPs functionalized with
      peptidic biomolecules was investigated with human fibroblasts (1BR3G) by ICP-MS
      analysis of the digested cells and confocal fluorescence microscopy, which showed
      increased internalization of the cationic bioconjugates. Nuclear targeting could
      be observed by TEM, suggesting that the cationic peptidic biomolecule is acting
      as a nuclear localization signal.

PMID- 22870983
TI  - Human adipose tissue-derived multilineage progenitor cells exposed to oxidative
      stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling.
AB  - BACKGROUND: Adipose tissues contain populations of pluripotent mesenchymal stem
      cells that also secrete various cytokines and growth factors to support repair of
      damaged tissues. In this study, we examined the role of oxidative stress on human
      adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in
      cells of the rat pheochromocytoma cell line (PC12). RESULTS: We found that
      glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine
      (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through
      upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor
      2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N
      acetylcysteine, a precursor of the intracellular antioxidant glutathione,
      suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO
      treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK
      was sufficient to suppress BMP2 and FGF2 expression, while this expression was
      significantly upregulated by overexpression of a constitutively active form of
      MKK6, which is an upstream molecule from p38 MAPK. CONCLUSIONS: Our results
      clearly suggest that glutathione depletion, followed by accumulation of reactive
      oxygen species, stimulates the activation of p38 MAPK and subsequent expression
      of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into
      neurodegenerative lesions such as stroke and Parkinson's disease, in which the
      transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple
      and safe therapies.

PMID- 22870985
TI  - Pulsed-field gel electrophoresis, conventional, and molecular serotyping of
      Listeria monocytogenes from food proficiency testing trials toward an
      harmonization of subtyping at European level.
AB  - The European Union Reference Laboratory for Listeria monocytogenes (EURL for L.
      monocytogenes) coordinates a European network of 29 National Reference
      Laboratories (NRLs). Depending on a national decision, NRLs undertake food,
      environmental, and veterinary L. monocytogenes strain surveillance in their
      respective countries. In the framework of the PulseNet Europe network, two pulsed
      field gel electrophoresis (PFGE) subtyping proficiency testing (PT) trials were
      carried out in 2003 and 2006. The obtained data showed that PFGE profiles can be
      compared and exchanged between laboratories. However, no further PT trial had
      been performed since 2006. In this context, two PT trials were organized by the
      EURL to evaluate the ability of NRLs to perform conventional serotyping,
      molecular serotyping and PFGE subtyping. Eleven well-characterized isolates of L.
      monocytogenes were used: six and nine isolates were tested in 2009 and 2010,
      respectively. Three isolates were repeated between the two studies. In the 2010
      panel, a strain was tested in duplicate, and two strains were related to the same
      epidemiological group. The strains were analyzed blind in different laboratories
      (17 in 2009 and 25 in 2010) using (1) their own in-house method for serotyping
      methods and (2) standardized protocols based on the PulseNet protocol for PFGE.
      For conventional serotyping, 86.0% in 2009 and 91.0% in 2010 of the serotypes
      obtained were in agreement with the EURL data. For molecular serotyping, 93.5% of
      the results in 2009 and 95.2% in 2010 matched the EURL data. For PFGE, 68.9% in
      2009 and 81.7% of the combined AscI/ApaI profiles were indistinguishable from the
      EURL reference profiles. The variations observed could be attributed to slight
      standardization defaults or, in a few cases, to a failure in DNA extraction.
      These PT trials provided a valuable opportunity to improve the subtyping ability
      of NRLs and facilitate exchanges of subtyping data in the future.

PMID- 22870986
TI  - A putative MerR family regulator involved in biofilm formation in Listeria
      monocytogenes 4b G.
AB  - The capability of forming biofilm makes the foodborne pathogen Listeria
      monocytogenes more resistant to environmental stresses. To examine the mechanism
      of biofilm formation, L. monocytogenes transposon mutant strain GB8 with
      decreased ability to form biofilm was characterized in this study. Southern blot
      assay revealed a single copy of transposon in the GB8 chromosome, and the
      insertion site was identified by inverse polymerase chain reaction (IPCR). The
      expression of lm.G_1497 was found to be inactivated by the transposon insertion,
      and the gene was identical to gene LMOf2365_1497 in the sequenced strain L.
      monocytogenes strain 4b F2365, encoding a MerR family protein. The ability of
      producing biofilm was recovered in revertant GBR8. It was confirmed by
      quantitative real-time PCR that the transcription of the gene flanking lm.G_1497
      was not affected by Tn917 insertion. These results suggested that lm.G_1497 was
      responsible for the positive regulation of biofilm formation in L. monocytogenes
      4b G. Moreover, the failure of lm.G_1497 expression resulted in a decrease of the
      autolysis rate, while no effect on cell growth and motility in L. monocytogenes
      GB8, which might imply that the reduction in biofilm was caused by the difference
      in cell autolysis.

PMID- 22870987
TI  - Protein folding: a problem with multiple solutions.
AB  - There is continued interest in predicting the structure of proteins either at the
      simplest level of identifying their fold class or persevering all the way to an
      atomic resolution structure. Protein folding methods have become very
      sophisticated and many successes have been recorded with claims to have solved
      the native structure of the protein. But for any given protein, there may be more
      than one solution. Many proteins can exist in one of the other two (or more)
      different forms and some populate multiple metastable states. Here, the two-state
      case is considered and the key structural changes that take place when the
      protein switches from one state to the other are identified. Analysis of these
      results show that hydrogen bonding patterns and hydrophobic contacts vary
      considerably between different conformers. Contrary to what has often been
      assumed previously, these two types of interaction operate essentially
      independently of one another. Core packing is critical for proper protein
      structure and function and it is shown that there are considerable changes in
      internal cavity volumes in many cases. The way in which these switches are made
      is fold dependent. Considerations such as these need to be taken into account in
      protein structure prediction.

PMID- 22870988
TI  - Human monocytes and macrophages differ in their mechanisms of adaptation to
      hypoxia.
AB  - INTRODUCTION: Inflammatory arthritis is a progressive disease with chronic
      inflammation of joints, which is mainly characterized by the infiltration of
      immune cells and synovial hyperproliferation. Monocytes migrate towards inflamed
      areas and differentiate into macrophages. In inflamed tissues, much lower oxygen
      levels (hypoxia) are present in comparison to the peripheral blood. Hence, a
      metabolic adaptation process must take place. Other studies suggest that Hypoxia
      Inducible Factor 1-alpha (HIF-1alpha) may regulate this process, but the
      mechanism involved for human monocytes is not yet clear. To address this issue,
      we analyzed the expression and function of HIF-1alpha in monocytes and
      macrophages, but also considered alternative pathways involving nuclear factor of
      kappa light polypeptide gene enhancer in B-cells (NFkappaB). METHODS: Isolated
      human CD14+ monocytes were incubated under normoxia and hypoxia conditions with
      or without phorbol 12-myristate 13-acetate (PMA) stimulation, respectively.
      Nuclear and cytosolic fractions were prepared in order to detect HIF-1alpha and
      NFkappaB by immunoblot. For the experiments with macrophages, primary human
      monocytes were differentiated into human monocyte derived macrophages (hMDM)
      using human macrophage colony-stimulating factor (hM-CSF). The effects of
      normoxia and hypoxia on gene expression were compared between monocytes and hMDMs
      using quantitative PCR (quantitative polymerase chain reaction). RESULTS: We
      demonstrate, using primary human monocytes and hMDM, that the localization of
      transcription factor HIF-1alpha during the differentiation process is shifted
      from the cytosol (in monocytes) into the nucleus (in macrophages), apparently as
      an adaptation to a low oxygen environment. For this localization change, protein
      kinase C alpha/beta 1 (PKC-alpha/beta1) plays an important role. In monocytes, it
      is NFkappaB1, and not HIF-1alpha, which is of central importance for the
      expression of hypoxia-adjusted genes. CONCLUSIONS: These data demonstrate that
      during differentiation of monocytes into macrophages, crucial cellular adaptation
      mechanisms are decisively changed.

PMID- 22870990
TI  - Identification of lubrication oil in the particulate matter emissions from engine
      exhaust of in-service commercial aircraft.
AB  - Lubrication oil was identified in the organic particulate matter (PM) emissions
      of engine exhaust plumes from in-service commercial aircraft at Chicago Midway
      Airport (MDW) and O'Hare International Airport (ORD). This is the first field
      study focused on aircraft lubrication oil emissions, and all of the observed
      plumes described in this work were due to near-idle engine operations. The
      identification was carried out with an Aerodyne high-resolution time-of-flight
      aerosol mass spectrometer (HR-ToF AMS) via a collaborative laboratory and field
      investigation. A characteristic mass marker of lubrication oil, I(85)/I(71), the
      ratio of ion fragment intensity between m/z = 85 and 71, was used to distinguish
      lubrication oil from jet engine combustion products. This AMS marker was based on
      ion fragmentation patterns measured using electron impact ionization for two
      brands of widely used lubrication oil in a laboratory study. The AMS measurements
      of exhaust plumes from commercial aircraft in this airport field study reveal
      that lubrication oil is commonly present in organic PM emissions that are
      associated with emitted soot particles, unlike the purely oil droplets observed
      at the lubrication system vent. The characteristic oil marker, I(85)/I(71), was
      applied to quantitatively determine the contribution from lubrication oil in
      measured aircraft plumes, which ranges from 5% to 100%.

PMID- 22870991
TI  - Classification of Sasang constitutional body types using immunostimulatory
      activities of constitution-specific herbal extracts in human primary immune
      cells.
AB  - Sasang is a Korean traditional constitutional medicine in which individuals are
      classified into four constitutional types: Taeyangin, Soeumin, Taeumin, and
      Soyangin. However, the classification of each constitution is empirical and not
      scientific, and so it is difficult to consistently classify patients into these
      four constitutional types. Acanthopanacis cortex (AC; Taeyangin), Rehmanniae
      radix (RR; Soyangin), Ephedra herba (EH; Taeumin), and White ginseng (WG;
      Soeumin) are herbal medicines that are used to treat and prevent diseases
      associated with these four constitutions. Therefore, AC, RR, EH, and WG extracts
      (ACE, RRE, EHE, and WGE) were used as reference extracts to determine
      constitutional differences in the immunostimulatory activities of primary immune
      cells isolated from the blood of 15 volunteers. Cellular proliferation, nitric
      oxide (NO), tumor necrosis factor-alpha (TNF-alpha) protein production, TNF-alpha
      and interleukin-6, and inducible NO synthase mRNA expression were measured as the
      immunostimulatory parameters. The increase in cell proliferation of V2, V3, V8,
      V11, and V12 was highest in EHE-treated lymphocytes among the ACE-, RRE-, EHE- or
      WGE-treated lymphocytes, and increase in cellular proliferation of V4, V7, V13,
      V14, and V15 in RRE-treated lymphocytes was significantly better than the other
      three medicines. The cell proliferation of V1, V5, V6, V9, and V10 responded best
      to WGE among the four extracts. Results of cell proliferation and other
      immunostimulatory parameters showed similar trends in regard to individual
      differences. These extracts may be useful as reference extracts in the
      development of a rapid and dependable individual lymphocyte- or macrophage-based
      assay that aids in the Sasang constitutional classification.

PMID- 22870992
TI  - Yield, quality, and concentration of seven heavy metals in cabbage and broccoli
      grown in sewage sludge and chicken manure amended soil.
AB  - The mobility of heavy metals from soil into the food chain and their subsequent
      bioaccumulation has increased the attention they receive as major environmental
      pollutants. The objectives of this investigation were to: i) study the impact of
      mixing native agricultural soil with municipal sewage sludge (SS) or chicken
      manure (CM) on yield and quality of cabbage and broccoli, ii) quantify the
      concentration of seven heavy metals (Cd, Cr, Mo, Cu, Zn, Pb, and Ni) in soil
      amended with SS or CM, and iii) determine bioavailability of heavy metals to
      cabbage leaves and broccoli heads at harvest. Analysis of the two soil amendments
      used in this investigation indicated that Cr, Ni, Cu, Zn, Mo, Cd, Pb, and organic
      matter content were significantly greater (P < 0.05) in premixed sewage sludge
      than premixed chicken manure. Total cabbage and broccoli yields obtained from SS
      and CM mixed soil were both greater than those obtained from no-mulch (bare)
      soil. Concentration of Ni in cabbage leaves of plants grown in soil amended with
      CM was low compared to plants grown in no-mulch soil. No significant differences
      were found in Cd and Pb accumulation between cabbage and broccoli. Concentrations
      of Ni, Cu, Zn, and Mo were greater in broccoli than cabbage. Total metals and
      plant available metals were also determined in the native and amended soils.
      Results indicated that the concentration of heavy metals in soils did not
      necessary reflect metals available to plants. Regardless of soil amendments, the
      overall bioaccumulation factor (BAF) of seven heavy metals in cabbage leaves and
      broccoli heads revealed that cabbage and broccoli were poor accumulators of Cr,
      Ni, Cu, Cd, and Pb (BAF <1), while BAF values were >1 for Zn and Mo. Elevated Ni
      and Mo bioaccumulation factor (BAF >1) of cabbage grown in chicken manure mixed
      soil is a characteristic that would be less favorable when cabbage is grown on
      sites having high concentrations of these two metals.

PMID- 22870993
TI  - Comparison of inflammatory responses in human cells caused by lipopolysaccharides
      from Escherichia coli and from indigenous bacteria in aquatic environment.
AB  - The endotoxic activities of lipopolysaccharides (LPSs) in water samples are
      usually determined using a Limulus amoebocyte lysate (LAL) assay, but it is known
      that the determined activities do not always represent their inflammatory potency
      in humans. In this investigation, the inflammatory responses in three different
      human cells stimulated with Escherichia coli LPS, keratinocyte, CD14(+) monocyte,
      and THP-1, were compared using cytokine secretion as biomarkers to develop novel
      in vitro assay systems for detecting changes in inflammatory potencies of
      endotoxins in aquatic environment. Only THP-1 with 6-h stimulation showed dose
      dependent responses in the range of normal endotoxin levels in aquatic
      environment. Then, the inflammatory potency of environmental LPS, which was
      purified from river water, was tested using THP-1. The levels and patterns of
      cytokine secretion after the environmental LPS stimulation were completely
      different from E. coli LPS. Interleukin 8 (IL-8) secretions after the
      environmental LPS stimulation were approximately 10-fold higher than those after
      E. coli LPS stimulation. The environmental LPS also induced much higher levels of
      TNF-alpha secretions in THP-1. These results suggest that a diversity of LPS
      structures in aquatic environment could contribute to stronger and different
      inflammatory responses. This investigation indicated that the proposed THP-1
      assay system could be useful for detecting the changes in inflammatory potencies
      caused by aquatic bacteria.

PMID- 22870994
TI  - Persistence and renaturation efficiency of thermally treated waste recombinant
      DNA in defined aquatic microcosms.
AB  - To validate the possibility of horizontal gene transfer (HGT) from thermally
      denatured recombinant DNA discharged into the eco-system, a constructed plasmid
      was used to investigate the persistence and renaturation efficiency of thermally
      denatured recombinant DNA in defined aquatic microcosms. The results revealed
      that there was undecayed recombinant plasmid pMDLKJ material being discharged
      into the aquatic microcosms even after thermal treatment at either 100 degrees C
      (using boiling water) or at 120 degrees C (using an autoclave). The plasmid had a
      relatively long persistence time. At least 10(2) copies MUL(-1) of a specific 245
      bp fragment of the plasmid could be detected after 12 h and a specific 628 bp
      fragment could be detected up to 2 h. The thermally denatured recombinant DNA
      could efficiently renature and recover its functional double stranded structure
      in aquatic microcosms and the highest concentration of double-stranded DNA
      (dsDNA) occurred around 1 h after the thermally denatured DNA was added to the
      system. These results imply that when thermally treated recombinant DNAs are
      discharged into aquatic environments, they have enough time to renature and
      possibly transfer to other organisms. In addition, the recombinant DNA added to
      aquatic microcosms could be absorbed by the seston particles in water, such as
      mineral, organic and colloids particles with a maximum absorption value of about
      5.18 ng L(-1). This absorbed DNA could persist longer in aquatic environments
      than free recombinant DNA, thus further favoring HGT.

PMID- 22870995
TI  - Pyrene degradation by Pseudomonas sp. and Burkholderia sp. enriched from coking
      wastewater sludge.
AB  - A pyrene-degrading consortium was enriched from sludge of coking wastewater
      treatment plant which included a combination of aerobic and anaerobic reactors.
      Biodegradation of pyrene by the consortium follows first-order kinetics. Addition
      of a co-substrate (glucose or anthraquinone) facilitated pyrene degrading. The
      highest degradation rate was achieved at 35 degrees C and pH 7.0, as glucose was
      added. In this case, pyrene (100 mg L(-1)) was degraded by 93.1 % within 36 h. An
      intermediate, 1-naphthol was detected via GC-MS analysis, indicating that pyrene
      degradation by the consortium proceeded with a pathway different from that
      associated with Mycobacterium sp. By comparisons of 16S rRNA gene sequences, two
      strains in this consortium were identified as Pseudomonas sp. and Burkholderia
      sp. The enriched pyrene-degrading consortium from coking wastewater treatment
      system shows highest pyrene-degrading activity compared with the reported pyrene
      degraders.

PMID- 22870996
TI  - Investigation of the inhibitory effects of heavy metals on heterotrophic biomass
      activity and their mitigation through the use of natural minerals.
AB  - This study examined the inhibitory effects of lead, copper, nickel and zinc on
      heterotrophic biomass and their potential mitigation through the use of low-cost,
      natural minerals. Activated sludge was placed in batch reactors and specific
      heavy metal concentrations were added. Subsequently, the biomass specific oxygen
      uptake rate (sOUR) was determined to assess the level of biomass inhibition.
      Biomass inhibition by heavy metals followed the order
      Cu(2+)>Pb(2+)>Zn(2+)>Ni(2+), with copper being the most toxic metal, causing high
      inhibition of heterotrophic biomass even at relatively low concentrations (i.e.
      10 mg.L(-1)). Zn had very small toxic effect at 10 mg.L(-1), while at 40 mg.L(-1)
      the level of biomass inhibition reached 80%. Nickel stimulated activated sludge
      activity at concentrations of the order of 10 mg.L(-1). The addition of 10 g.L(
      1) bentonite and zeolite in activated sludge resulted in the decrease of the
      inhibitory effect of heavy metals on biomass respiratory activity. In some cases,
      mineral addition was very favorable as inhibition was reduced from 69-90% to less
      than 55% and even up to 12%. The beneficial action of minerals is attributed both
      to the adsorption of heavy metals on the mineral and on the potential aggregation
      between mineral and sludge particles.

PMID- 22870997
TI  - Trends of atmospheric deposition of trace elements in Macedonia studied by the
      moss biomonitoring technique.
AB  - In 2002 and 2005 the moss biomonitoring technique was applied to air pollution
      studies in the Republic of Macedonia in the framework of the International
      Cooperative Programme on Effects of Air Pollution on Natural Vegetation and Crops
      under the auspices of the United Nations Economic Commission for Europe (UNECE
      ICP Vegetation) Convention on Long-Range Transboundary Air Pollution (LRTAP). In
      August 2005 samples of the terrestrial mosses Homolothecium lutescens and Hypnum
      cupressiforme were collected at 72 sites evenly distributed over the territory of
      the country, in accordance with the sampling strategy of the European moss survey
      programme. A total of 41 elements (Na, Mg, Al, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe,
      Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, Zr, Mo, Cd, Sb, I, Cs, Ba, La, Ce, Sm, Eu,
      Tb, Dy Hf, Ta, W, Hg, Pb, Th, and U) were determined by instrumental epithermal
      neutron activation analysis and atomic absorption spectrometry. Principal
      component analysis was used to identify and characterize different pollution
      sources. Distributional maps were prepared to point out the regions most affected
      by pollution and to relate this to known sources of contamination. A few areas,
      as in 2002, are experiencing particular environmental stress: Veles, Skopje,
      Tetovo, Radovis and Kavadarci-Negotino, whereas the agricultural regions in the
      south, south-west, and south-east show median European values for most elements
      of mainly pollution origin. A significant increase in the content of Ni is
      noticed in the 2005 moss survey compared with 2002, due to the increased
      production of the ferro-nickel smelter in Kavadarci. A higher content of Cd, Hg,
      and Pb in 2005 relative to 2002 can be explained by pollution from the lead-zinc
      smelter in Veles, as well as the pollution that comes from the open slag waste
      dump of this smelter. Protection activities on the dump of slag from the former
      ferrochromium smelter located near Tetovo resulted in a lower content of Cr in
      the 2005 moss survey.

PMID- 22870998
TI  - PIXE analysis of PM2.5 and PM(2.5-10) for air quality assessment of Islamabad,
      Pakistan: application of chemometrics for source identification.
AB  - A Gent sampler was used to collect 379 pairs of filters from Nilore, a suburban
      area of Islamabad city. The study was designed to assess the concentration
      variations of trace elements in fine and coarse particulate matter due to
      anthropogenic activities and naturally occurring events. Source identification
      was performed by applying MATLAB software for principal component analysis (PCA),
      and cluster analysis (CA). The average fine and coarse particulate masses during
      the study period were 15.1 +/- 11.9 and 37.3 +/- 28.0 MUg/m(3) respectively which
      complies with the 24-h air quality limits set by the government of Pakistan. The
      application of PCA to PM(2.5) data suggests the PM contribution from sources such
      as soil, automobile exhaust and coal combustion, road dust and wearing of tyres,
      wood combustion, biomass burning and fertilizers and fungicides whereas for the
      PM(2.5-10) data shows signatures of suspended soil, automobile exhaust, road dust
      and wearing of tyres, wood and biomass burning, refuse incineration, Ni smelter,
      fertilizers and fungicides are obtained. Cluster analysis of PM(2.5) and PM(2.5
      10) datasets reveals that there are mainly three contributory pollution sources
      and these are suspended soil particles, automobile related sources and wood and
      coal combustion.

PMID- 22870999
TI  - Nitrate reduction by commercially available nitrate reductases: bio-catalytic
      potentials and enzymatic activities in the presence of metals ions.
AB  - Commercially available nitrate reductases from corn, Aspergillus niger, and
      Escherichia coli have the potential to mitigate excess nitrate in soils and water
      sources. In this study, in vitro experiments were conducted to evaluate nitrate
      reduction by commercially available nitrate reductases from three major sources
      (plant, fungi and bacteria), their biocatalytic potentials and activities in the
      presence of varied concentrations of Cd(2+), Cu(2+), Ni(2+), Co(2+), Cr(6+),
      Fe(2+), Zn(2+), and Pb(2+). The results showed that the activity, V (max), and
      potential to reduce nitrate was in the order: corn > A. niger > E. coli. The
      kinetic constant (K (m)) based on the various substrates used demonstrated that
      the binding affinity was generally highest for E. coli and lowest for A. niger.
      Based on the specificity constants obtained in this study, nitrate reductase from
      corn was the most efficient of all the enzymes assayed, yet that from E. coli
      showed the least. Nitrate reductase from corn and A. niger showed more variations
      with increase in metal ions concentrations compared to E. coli (with the
      exception of Cu(2+)). Information reported in this study will enable the
      assessment of the contributions and sources of nitrate reductases in mitigating
      environmental and health issues resulting from nitrate pollution.

PMID- 22871000
TI  - Preparation of Mg-Al layered double hydroxide intercalated with Coomassie
      Brilliant Blue R anion and its uptake of aromatic compounds from aqueous
      solutions.
AB  - The objective of this study is to evaluate the capacity of Mg-Al layered double
      hydroxide (Mg-Al LDH) intercalated with organic dye to adsorb aromatic compounds
      in aqueous solutions. Mg-Al LDH intercalated with Coomassie Brilliant Blue R
      anion (BB(-)) was prepared by coprecipitation. The BB(-)-intercalated Mg-Al LDH
      was able to adsorb aromatic compounds from an aqueous solution, despite the
      electron density in the benzene ring of the aromatics. This uptake is caused by
      pi-pi stacking interactions, either between the electron-rich benzene rings of
      intercalated BB(-) and the benzene rings of aromatics with a low electron density
      or between the electron-poor benzene rings of intercalated BB(-) and the benzene
      rings of the aromatics with a high electron density.

PMID- 22871001
TI  - Electrochemical treatment of dye-bath effluent by stainless steel electrodes:
      multiple response optimization and residue analysis.
AB  - The aim of this article is to maximize the chemical oxygen demand (COD) and color
      removal, and simultaneously minimize the energy consumed per unit mass of COD
      removed for the treatment of dye-bath effluent (DBE) by electrochemical (EC)
      method using stainless steel (SS) electrode in a batch EC reactor. Response
      surface methodology involving central composite design was employed to optimize
      the multiple responses. The effects of operating parameters such as pH of DBE,
      and important process parameters such as current density, electrolysis time and
      inter electrode space were studied. At the optimized condition, 91.7% COD removal
      and 99.8% color removal was observed with energy consumption of 7.71 kWh/kg of
      COD removed. Finally, the thermogravimetric analysis of the EC scum and sludge
      has been done in oxidizing atmosphere so as to evaluate their disposal aspects.

PMID- 22871002
TI  - Polyhydroxyalkanoate biosynthesis from paper mill wastewater treated by a moving
      bed biofilm reactor.
AB  - Polyhydroxyalkanoate (PHA) biosynthesis in paper mill wastewater treated by a
      Moving Bed Biofilm Reactor (MBBR) was evaluated. A MBBR was operated during 300
      d. The increasing effect of the Organic Load Rate (OLR) from 0.13 kg
      BOD(5)/m(3).d to 2.99 kg BOD(5)/m(3).d and the influence of two relationship of
      BOD(5:) N: P (100: 5: 1 and 100: 1: 0.3) on the PHA biosynthesis were evaluated.
      With an OLR of 0.13 kg BOD(5)/m(3).d, the maximum organic matter removal measure
      as Biochemical Oxygen Demand (BOD(5)) was 98.7% for a BOD(5:) N: P relationship
      of 100: 5: 1. Meanwhile for BOD(5): N: P relationship of 100: 1: 0.3, the maximum
      efficiency was 87.2% (OLR: 2.99 kg BOD(5)/m(3).d). The behaviour of the Chemical
      Oxygen Demand (COD) and total phenolic compound removal efficiencies were below
      65.0% and 41.0%, respectively. PHA biosynthesis was measured as a percentage of
      cells that accumulate PHA, where the maximum percentage was 85.1% and 78.7% when
      MBBR was operated under a BOD(5): N: P relationship of 100: 5: 1 and 100: 1: 0.3,
      respectively. Finally, the PHA yields in this study were estimated to range
      between 0.11 to 0.72 mg PHA/mg VSS and 0.06 to 0.15 mg PHA/mg COD.

PMID- 22871003
TI  - Bacteriophage removal by Ni/Al layered double hydroxide in batch and flow-through
      column experiments.
AB  - The objective of this study was to investigate the removal of the bacteriophage
      MS2 by Ni/Al layered double hydroxide (LDH). Batch experiments were performed
      using a powder form of Ni/Al LDH under various conditions. Column experiments
      were also performed under flow-through conditions with Ni/Al LDH coated sand.
      Batch tests showed that the powder form of Ni/Al LDH was effective for
      bacteriophage removal under the given experimental conditions (LDH dose of 2.5 g
      L(-1); initial MS2 concentration of 1.35 * 10(5) plaque forming unit (pfu) mL(
      1)) with a removal capacity of 5.5 * 10(7) pfu g(-1). The results also indicated
      that the effect of the solution pH on the bacteriophage removal was minimal at pH
      4.3-9.4. The influence of divalent anions (SO(2-) (4), CO(2-) (3), HPO(2-) (4);
      concentrations 1-100 mM) on the removal of the bacteriophage was significant,
      while the effects of monovalent anions (NO(-) (3), Cl(-)) were negligible. Column
      experiments showed that the log removal of MS2 was 4.51 in columns containing
      100% Ni/Al LDH-coated sand, while it was 0.02 in columns containing 100% quartz
      sand (initial MS2 concentration of approximately 7.0 * 10(5) pfu mL(-1); flow
      rate of 0.5 mL min(-1)). These findings indicated that Ni/Al LDH-coated sand was
      far more effective at removing bacteriophage than sand alone. This study
      demonstrates that Ni/Al LDH can be used for virus removal in water treatment and
      filtration applications.

PMID- 22871004
TI  - Evaluating coagulation pretreatment on poultry processing wastewater for
      dissolved air flotation.
AB  - Eleven metal coagulants and one polyelectrolyte were assessed for their
      suitability in assisting a dissolved air flotation (DAF) system aimed at treating
      poultry processing wastewater. Preliminary jar tests determined that a
      combination of 800 mg/L of FeCl(3) (ferric chloride) and 900 mg/L of Floccin 1115
      would provide the best treatment by removing at least 98% of the total suspended
      solids (TSS) and 97% of the volatile suspended solids (VSS), while providing a
      97% increase in water clarity. Final flotation tests suggested that the
      flocculated particles could be carried to the surface with 40% recycle ratio of
      the DAF. The resulting supernatant indicated 94.7% increase in clarity (+/-
      1.4%), 97.3% reduction in TSS (+/- 0.5%), 96.6% reduction in VSS (+/-1.1%), 91%
      reduction in chemical oxygen demand (COD), and nearly 100% removal of fats, oils,
      and greases (FOGs). Despite the high removal efficiencies, flotation was found
      not to be critically necessary for treatment because the high concentration of
      coagulants caused settling of the flocs to occur just as rapidly. Potential
      coagulant overdosing is suspected at the higher end of the tested coagulant
      concentrations due to limited alkalinity in the wastewater. However, lack of
      residual metal (coagulant) ions in water may be linked to reactions leading to
      phosphate precipitation. The exact effect of the competing phosphate reaction on
      treatment efficiency is not clearly evident from this present study.

PMID- 22871005
TI  - Comparison of UV and UV/H2O2 treatments using excilamps for removal of
      monochlorophenols in the molecular and anionic form.
AB  - The efficiency of UV/H(2)O(2) treatment using KrCl (222 nm) and XeBr (282 nm)
      excilamps was examined for removal of 2-chlorophenol (2-CP) and 4-chlorophenol (4
      CP) from aqueous solution in the molecular form (pH 2 and un-adjusted pH) and
      anionic form (at pH 11). UV/H(2)O(2) treatment of 2- or 4-CP was initially
      carried out at un-adjusted pH with varying molar ratios of chlorophenol and
      H(2)O(2). The para-chlorobenzoic acid was used as a hydroxyl radical (*OH) probe
      compound. UV/H(2)O(2) treatment of 2- and 4-CP with a molar ratio of 1:25 at
      ambient pH and a fluence of 4.1 J/cm(2) provided a significant decrease in
      chemical oxygen demand (COD). Under these conditions, the *OH exposure was found
      to increase from 0.5 * 10(-11) and 0.4 * 10(-11) to 1.8 * 10(-11) and 1.3 * 10(
      11) M min for KrCl and XeBr excilamp, respectively. Compared with direct UV
      photolysis, the pseudo-first-order fluence-based rate constants of 2- and 4-CP
      degradation in UV/H(2)O(2) process at a molar ratio of 1:25 were significantly
      higher for molecular 2-CP and 4-CP in the anionic form using both excilamps.
      Detailed information on UV fluence and/or the exposure to *OH radicals is
      proposed to accurately compare studies reporting the effectiveness of AOPs based
      on excilamps.

PMID- 22871006
TI  - Stripping voltammetric determination of palladium, platinum and rhodium in
      freshwater and sediment samples from South African water resources.
AB  - Stripping voltammetry as technique has proved to be very useful in the analysis
      of heavy and other metal ions due to its excellent detection limits and its
      sensitivity in the presence of different metal species or interfering ions.
      Recent assessments of aquatic samples have shown increased levels of platinum
      group metals (PGMs) in aquatic ecosystems, caused by automobile exhaust emissions
      and mining activities. The development of an analytical sensor for the detection
      and characterisation of PGMs were investigated, since there is an ongoing need to
      find new sensing materials with suitable recognition elements that can respond
      selectively and reversibly to specific metal ions in environmental samples. The
      work reported shows the successful application of another mercury-free sensor
      electrode for the determination of platinum group metals in environmental
      samples. The work reported in this study entails the use of a glassy carbon
      electrode modified with a bismuth film for the determination of platinum
      (Pt(2+)), palladium (Pd(2+)) or rhodium (Rh(2+)) by means of adsorptive cathodic
      stripping voltammetry. Optimised experimental conditions included composition of
      the supporting electrolyte, complexing agent concentration, deposition potential,
      deposition time and instrumental voltammetry parameters for Pt(2+), Pd(2+) and
      Rh(2+) determination. Adsorptive differential pulse stripping voltammetric
      measurements for PGMs were performed in the presence of dimethylglyoxime (DMG) as
      complexing agent. The glassy carbon bismuth film electrode (GC/BiFE) employed in
      this study exhibit good and reproducible sensor characteristics. Application of
      GC/BiFE sensor exhibited well-defined peaks and highly linear behaviour for the
      stripping analysis of the PGMs in the concentration range between 0 and 3.5
      MUg/L. The detection limit of Pd, Pt and Rh was found to be 0.12 MUg/L, 0.04
      MUg/L and 0.23 MUg/L, respectively for the deposition times of 90 s (Pd) and 150
      s (for both Pt and Rh). Good reproducibility was also observed and the practical
      applicability of the sensor was demonstrated with the analysis of environmental
      water and sediment samples.

PMID- 22871007
TI  - Mercury in Yellow-cracking Boletes Xerocomus subtomentosus mushrooms and soils
      from spatially diverse sites: assessment of bioconcentration potential by species
      and human intake.
AB  - This study investigated the Hg concentrations in Yellow-cracking Boletes
      Xerocomus subtomentosus mushrooms and beneath soils collected from the wild at
      twelve sites across Poland. This mushroom species has some potential to
      bioconcentrate Hg in the fruiting bodies, and the amount of Hg sequestered,
      depending on geographical location, can pose health risk to consumers. The values
      of Hg bioconcentration factor (BCF) varied for the sites between 0.80 +/- 0.20
      and 17 +/- 12 in caps and 0.50 +/- 0.10 and 7.9 +/- 6.6 in stipes of fruiting
      bodies but decreased as soil Hg content increased from 72 +/- 32 to 570 +/- 130
      ng/g dry weight. The specimens collected from minerals rich area of Zlotoryja
      contained the highest Hg concentration, which reached 630 +/- 400 in caps and 420
      +/- 260 ng/g dw in stipes, while the lowest observed Hg concentrations at the
      other sites were 72 +/- 32 and 57 +/- 13 ng/g, for cap and stipes respectively.
      Available literature data on Hg in Yellow-cracking Boletes was also up-dated.

PMID- 22871008
TI  - Cadmium, lead and mercury concentrations in selected red deer (Cervus elaphus L.)
      tissues from north-eastern Croatia.
AB  - Concentrations of cadmium, lead and mercury were determined in muscle, liver and
      kidney tissue from three different age groups of red deer (young animals aged 6
      or 7 months, middle-aged animals aged 3 to 5 years, old animals aged over 8
      years) from the Baranja region of Croatia. Median cadmium concentrations were low
      in the muscles of all investigated age groups (0.0002; 0.0009 and 0.0020 MUg/g),
      higher in the liver (0.0279; 0.0656 and 0.1463 MUg/g) and highest in the kidneys
      (0.4792; 2.8531 and 6.1657 MUg/g). A positive correlation was established between
      cadmium concentration and age. In all analyzed tissues the median lead
      concentration was higher in young (muscle 0.0024; liver 0.0364 and kidney 0.0618
      MUg/g), compared to middle-aged animals (muscle 0.0001; liver 0.0184 and kidney
      0.0160 MUg/g). In contrast to cadmium, mercury had a negative correlation to age
      but median concentrations were very low (in muscle: 0.0011; 0.0001 and 0.0006
      MUg/g; in liver: 0.0051; 0.0037 and 0.0022 MUg/g and in kidney: 0.0145; 0.0183
      and 0.0106 MUg/g) especially compared to cadmium. From the hygienic point of view
      all the examined tissues are edible since concentrations of the analyzed metals
      do not exceed values proposed by the official regulations, with the exception of
      a few kidney samples, which contained cadmium above the recommended value.
      Furthermore, mercury concentrations are no longer (since 2008) a matter of
      legislation.

PMID- 22871009
TI  - Heterogeneous photocatalysis of real textile wastewater: evaluation of reaction
      kinetics and characterization.
AB  - Real textile wastewater collected from the cotton dyeing bath of a fabric dyeing
      and finishing plant was subjected to heterogeneous photocatalysis using Ag(+)
      doped TiO(2) under UV irradiation in a batch reactor. The photocatalysts were
      characterized by FESEM, XRD, EDS, FTIR, DRS and BET analyses. The kinetics of the
      reaction was also evaluated. Colour removal was more than 88%, 94% and 99%,
      respectively for undiluted, 2 times diluted and 5 times diluted wastewater with
      Ag(+) doped TiO(2) (2.5 g/L) after UV irradiation for 360 minutes. The COD
      removal for undiluted, 2 times diluted and 5 times diluted wastewater was 47%,
      70% and 92%, respectively under similar conditions. The reaction followed
      Langmuir-Hinshelwood pseudo first order kinetic model and the data fitted well to
      polynomial regression analysis.

PMID- 22871010
TI  - Development of an HPLC method to analyze four veterinary antibiotics in soils and
      aqueous media and validation through fate studies.
AB  - A simple, yet robust analytical method was developed to detect and quantify three
      sulfonamides (SA), namely sulfamethoxazole (SMO), sulfachloropyridazine (SCP),
      and sulfamethazine (SM), and a macrolide tylosin (TT) in aqueous (calcium
      chloride and leachate solutions) and solid (agricultural soils) matrices using
      high performance liquid chromatography and ultra violet detection at 290 nm (TT)
      and 275 nm (SA) respectively. Chromatography was performed using a Phenomenex
      Onyx Monolithic C(18) column for TT and a C(18) Luna column for sulfonamides as
      single analytes eluted isocratically with a mobile phase consisting of
      acetonitrile: trifluoroacetic acid: tetrahydrofuran in the ratio 22.5:68:9.5 for
      TT, 40:55:5 for SMO, 32:63:5 for SCP and 31:64:5 for SM (v/v) at 1.0 mL min(-1)
      and an injection volume of 20 MUL. A gradient method to detect all three
      sulfonamides in a single run was also developed. The soil residue analysis
      consisted of extraction with dichloromethane and pre-concentration steps as the
      aqueous phase was measured directly. The limits of detection at an S/N (signal:
      noise) ratio of 3 were 20.0 MUg L(-1) and 50 MUg L(-1) for all sulfonamides and
      tylosin respectively. The average recoveries for all sulfonamides and tylosin in
      aqueous matrices ranged from 95 to 105% across the six concentrations
      investigated. Recoveries from the soils were slightly lower for sulfonamides and
      tylosin. The isocratic method was used to determine the sorption and degradation
      of sulfonamides in soils, while the gradient method was used to determine
      degradation kinetics and leachate concentrations in soils and aqueous systems.

PMID- 22871011
TI  - Retention of selected steroids on a silt-loam soil.
AB  - This study used batch-equilibrium techniques to evaluate the soil sorption and
      desorption of target steroids, representative of the estrogen, androgen,
      progestogen and corticosteroid families. The sorption kinetics exhibited an
      immediate rapid sorption followed by a slow process with a duration dependent on
      soil particle size. Adsorption and desorption isotherms could be described by the
      Freundlich equation, in a non-linear form (1/n < 1). High organic carbon-water
      partitioning coefficient (K(OC)) values indicate that a large mass fraction of
      the hormones will be associated with the sorbed phase. As a result of the poor
      linear correlation between log K(OC) and log K(OW) (octanol-water partition
      coefficient), it could be assumed that both hydrophobic and hydrogen bonding
      interactions contribute to the sorption mechanisms of the selected steroids. A
      hysteresis phenomenon was observed, varying with particle size, indicating strong
      irreversible interactions between some steroids and soil.

PMID- 22871012
TI  - Solar photo-Fenton treatment of carbofuran: analysis of mineralization, toxicity,
      and organic by-products.
AB  - The degradation of the pesticide carbofuran (CBF) using solar photo-Fenton
      treatment, at both the laboratory and the pilot scale, was evaluated. At the
      laboratory scale, in a suntest reactor, the Fe(2+) concentration and H(2)O(2)
      concentration were evaluated and optimized using the surface response methodology
      and the Pareto diagram. Under optimal conditions experiments were performed to
      evaluate the evolution of the substrate removal, oxidation, subsequent
      mineralization, toxicity and the formation of chloride ions during the treatment.
      The analysis and evolution of five CBF by-products as well as several control and
      reactivity tests at the density functional theory level were used to depict a
      general scheme of the main degradation pathway of CBF via the photo-Fenton
      system. Finally, at the pilot scale, a sample of the commercial CBF product
      Furadan was eliminated after 420 min by the photo-Fenton system using direct
      sunlight. Under these conditions, after 900 min 89% of toxicity (1/E(50) on
      Vibrio fischeri bacteria), 97% of chemical oxygen demand, and 90% of dissolved
      organic carbon were removed.

PMID- 22871013
TI  - Microbial degradation of pharmaceuticals followed by a simple HPLC-DAD method.
AB  - The biodegradation of five pharmaceutical ingredients (PIs) of different
      therapeutic classes, namely antibiotics (trimethoprim, sulfametoxazole and
      ciprofloxacin), anti-inflammatory (diclofenac) and anti-epileptic
      (carbamazepine), by two distinct microbial consortia, was investigated. For the
      monitoring of biodegradation assays, a simple HPLC-DAD (High Performance Liquid
      Chromatography - Diode Array Detector) method was developed and validated. The
      separation of the target pharmaceuticals was performed using an environmental
      friendly mobile phase in a gradient mode of 0.1% triethylamine (TEA) in water
      acidified at pH 2.23 with trifluoroacetic acid (TFAA) and ethanol as organic
      solvent. The method revealed to be selective, linear and precise in the range of
      1.0 to 30.0 MUg/mL for all PIs. Biodegradation assays were performed using
      activated sludge and a bacterial consortium (able to degrade fluoroaromatic
      compounds) supplemented with the target PIs at a final concentration of 25
      MUg/mL. The results revealed that activated sludge removed the target compounds
      more efficiently than the bacterial consortium.

PMID- 22871014
TI  - Relative efficiency of multi-transect, non-pumped, reactive well networks for
      removing contaminated groundwater.
AB  - Alternative networks of non-pumped wells filled with reactive media were
      evaluated for groundwater remediation capability. Wells were screened across the
      saturated zone of a simulated, unconfined aquifer with a heterogeneous hydraulic
      conductivity. A numerical mass transport model generated an initial contaminant
      plume and then simulated its movement through different networks of non-pumped
      wells. Two cases were investigated: (1) a linear transect of wells downgradient
      of the plume; and (2) a downgradient linear transect combined with a second
      linear transect crossing the plume's interior. Several simulations were conducted
      for each case to determine the smallest number of wells necessary to prevent the
      plume from traveling offsite. Case 2 required 11% more wells, but reduced cleanup
      time by 21%.

PMID- 22871015
TI  - Natural radioactivity of riverbank sediments of the Maritza and Tundja Rivers in
      Turkey.
AB  - This article represents the first results of the natural radionuclides in the
      Maritza and Tundja river sediments, in the vicinity of Edirne city, Turkey. The
      aim of the article is to describe the natural radioactivity concentrations as a
      baseline for further studies and to obtain the distribution patterns of
      radioactivity in trans-boundary river sediments of the Maritza and Tundja, which
      are shared by Turkey, Bulgaria and Greece. Sediment samples were collected during
      the period of August 2007-April 2010. The riverbank sediment samples were
      analyzed firstly for their pH, organic matter content and soil texture. The gross
      alpha/beta and (238)U, (232)Th and (40)K activity concentrations were then
      investigated in the collected sediment samples. The mean and standard error of
      mean values of gross alpha and gross beta activity concentrations were found as
      91 +/- 11, 410 +/- 69 Bq/kg and 86 +/- 11, 583 +/- 109 Bq/kg for the Maritza and
      Tundja river sediments, respectively. Moreover, the mean and standard error of
      mean values of (238)U, (232)Th and (40)K activity concentrations were determined
      as 219 +/- 68, 128 +/- 55, 298 +/- 13 and as 186 +/- 98, 121 +/- 68, 222 +/- 30
      Bq/kg for the Maritza and Tundja River, respectively. Absorbed dose rates (D) and
      annual effective dose equivalent s  have been calculated for each sampling point.
      The average value of adsorbed dose rate and effective dose equivalent were found
      as 191 and 169 nGy/h; 2 and 2 mSv/y for the Maritza and the Tundja river
      sediments, respectively.

PMID- 22871016
TI  - The association between some endocrine disruptors and hypospadias in biological
      samples.
AB  - Hypospadias is a birth defect found in boys in which the urinary tract opening is
      not at the tip of the penis. The etiology of hypospadias is still unidentified,
      but endocrine disruptors are considered as one possible cause of hypospadias. In
      this study, target endocrine disruptor compounds were established for an assay.
      The target compounds included 5 phthalates (di-(2-ethylhexyl)phthalate (DEHP), di
      n-butyl-phthalate (DBP), mono-(2- ethylhexyl) phthalate (MEHP), mono-n-butyl
      phthalate (MBP) and phthalic acid (PA)), 2 alkylphenols (n-nonylphenol (n-NP) and
      t-octylphenol (t-OP)) and bisphenol A. The association between these 8 endocrine
      disruptors and hypospadias was studied. The levels of endocrine disruptors in the
      urine and plasma of a control group were compared with those of a patient group.
      DEHP (P = 0.006) and n-NP (P = 7.26e-6) in the urine samples and PA (P = 0.009)
      and BPA (P = 7.22e-10) in the plasma samples showed a significant association
      with hypospadias. The levels of endocrine disruptors in the urine and plasma of
      the mothers were also compared to those of the patients to investigate the
      metastasis of the endocrine disruptors from the mother. These levels did not,
      however, show a relationship with hypospadias (R(2) = 0.001-0.563).

PMID- 22871019
TI  - Isolated central nervous system relapse of chronic myeloid leukemia after
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: This case report highlights the relevance of quantifying the BCR-ABL
      gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid
      leukemia in the central nervous system. CASE PRESENTATION: We report on a female
      patient with isolated central nervous system relapse of chronic myeloid leukemia
      (CML) during peripheral remission after allogeneic hematopoietic stem cell
      transplantation. The patient showed a progressive cognitive decline as the main
      symptom. MRI revealed a hydrocephalus and an increase in cell count in the
      cerebrospinal fluid (CSF) with around 50% immature blasts in the differential
      count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the
      ratio for peripheral blood and bone marrow was not altered. On treatment of the
      malresorptive hydrocephalus with shunt surgery, the patient showed an initial
      cognitive improvement, followed by a secondary deterioration. At this time, the
      cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence,
      intrathecal administration of cytarabine, methotrexate, and dexamethasone was
      initiated, which caused a significant decrease of cells in the CSF. Soon after,
      the patient demonstrated significant cognitive improvement with a good
      participation in daily activities. At a later time point, after the patient had
      lost the major molecular response of CML, therapy with dasatinib was initiated.
      In a further follow-up, the patient was neurologically and hematologically
      stable. CONCLUSIONS: In patients with treated CML, the rare case of an isolated
      CNS blast crisis has to be taken into account if neurological symptoms evolve.
      The analysis of BCR-ABL in the CSF is a further option for the reliable detection
      of primary isolated relapse of CML in these patients.

PMID- 22871020
TI  - The design of a real-time formative evaluation of the implementation process of
      lifestyle interventions at two worksites using a 7-step strategy (BRAVO@Work).
AB  - BACKGROUND: Worksite health promotion programs (WHPPs) offer an attractive
      opportunity to improve the lifestyle of employees. Nevertheless, broad scale and
      successful implementation of WHPPs in daily practice often fails. In the present
      study, called BRAVO@Work, a 7-step implementation strategy was used to develop,
      implement and embed a WHPP in two different worksites with a focus on multiple
      lifestyle interventions.This article describes the design and framework for the
      formative evaluation of this 7-step strategy under real-time conditions by an
      embedded scientist with the purpose to gain insight into whether this this 7-step
      strategy is a useful and effective implementation strategy. Furthermore, we aim
      to gain insight into factors that either facilitate or hamper the implementation
      process, the quality of the implemented lifestyle interventions and the degree of
      adoption, implementation and continuation of these interventions. METHODS AND
      DESIGN: This study is a formative evaluation within two different worksites with
      an embedded scientist on site to continuously monitor the implementation process.
      Each worksite (i.e. a University of Applied Sciences and an Academic Hospital)
      will assign a participating faculty or a department, to implement a WHPP focusing
      on lifestyle interventions using the 7-step strategy. The primary focus will be
      to describe the natural course of development, implementation and maintenance of
      a WHPP by studying [a] the use and adherence to the 7-step strategy, [b] barriers
      and facilitators that influence the natural course of adoption, implementation
      and maintenance, and [c] the implementation process of the lifestyle
      interventions. All data will be collected using qualitative (i.e. real-time
      monitoring and semi-structured interviews) and quantitative methods (i.e. process
      evaluation questionnaires) applying data triangulation. Except for the real-time
      monitoring, the data collection will take place at baseline and after 6, 12 and
      18 months. DISCUSSION: This is one of the few studies to extensively and
      continuously monitor the natural course of the implementation process of a WHPP
      by a formative evaluation using a mix of quantitative and qualitative methods on
      different organizational levels (i.e. management, project group, employees) with
      an embedded scientist on site. TRIAL REGISTRATION: NTR2861.

PMID- 22871021
TI  - Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study
      for the NorCAPITAL trial.
AB  - BACKGROUND: This pilot study (ClinicalTrials.gov ID: NCT01507701) assessed the
      feasibility and safety of clonidine in adolescent chronic fatigue syndrome (CFS).
      Specifically, we assessed clonidine dosage in relation to a) plasma concentration
      levels, b) orthostatic cardiovascular responses, and c) possible adverse effects.
      FINDINGS: Five adolescent CFS patients (14-19 years old) received 50 MUg
      clonidine twice per day during 14 days in an open, uncontrolled design. Plasma
      concentration of clonidine was assayed by standard laboratory methods. Changes in
      orthostatic cardiovascular responses were assessed by a 20o head-up tilt-test
      (HUT). Adverse effects were mapped by a questionnaire.After 14 days, C0 median
      (range) of clonidine was 0.21 (0.18-0.36) MUg/L, and Cmax median (range) of
      clonidine was 0.41 (0.38-0.56) MUg/L. Also, supine blood pressures and heart rate
      were lower during clonidine treatment, and the HUT response was closer to the
      normal response. No serious adverse effects were registered. CONCLUSION:
      Clonidine 50 MUg BID seems to be safe enough to proceed from a pilot study to a
      controlled trial in a select group of adolescents with CFS (ClinicalTrials.gov
      ID: NCT01040429).

PMID- 22871022
TI  - Phytochemicals as chemosensitizers: from molecular mechanism to clinical
      significance.
AB  - This review provides an overview of the clinical relevance of chemosensitization,
      giving special reference to the phenolic phytochemicals, curcumin, genistein,
      epigallocatechin gallate, quercetin, emodin, and resveratrol, which are potential
      candidates due to their ability to regulate multiple survival pathways without
      inducing toxicity. We also give a brief summary of all the clinical trials
      related to the important phytochemicals that emerge as chemosensitizers. The mode
      of action of these phytochemicals in regulating the key players of the death
      receptor pathway and multidrug resistance proteins is also abridged. Rigorous
      efforts in identifying novel chemosensitizers and unraveling their molecular
      mechanism have resulted in some of the promising candidates such as curcumin,
      genistein, and polyphenon E, which have gone into clinical trials. Even though
      considerable research has been conducted in identifying the salient molecular
      players either contributing to drug efflux or inhibiting DNA repair and
      apoptosis, both of which ultimately lead to the development of chemoresistance,
      the interdependence of the molecular pathways leading to chemoresistance is still
      the impeding factor in the success of chemotherapy. Even though clinical trials
      are going on to evaluate the chemosensitizing efficacy of phytochemicals such as
      curcumin, genistein, and polyphenon E, recent results indicate that more intense
      study is required to confirm their clinical efficacy. Current reports also
      warrant intense investigation about the use of more phytochemicals such as
      quercetin, emodin, and resveratrol as chemosensitizers, as all of them have been
      shown to modulate one or more of the key regulators of chemoresistance.

PMID- 22871023
TI  - The chronic care model: congruency and predictors among patients with
      cardiovascular diseases and chronic obstructive pulmonary disease in the
      Netherlands.
AB  - BACKGROUND: The Chronic Care Model (CCM) achieved widespread acceptance and
      reflects the core elements of patient-centred care in chronic diseases such as
      CVD and COPD. Our aim is to assess the extent to which current care for CVD and
      COPD patients aligns with the CCM in Dutch healthcare practices in the early
      stages of implementing disease-management programmes, thereby revealing possible
      predictors that tell us whether certain patients are more likely to receive CCM
      compliant care than others. METHODS: We use a cross-sectional study, addressing
      CVD or COPD patients from 106 primary care practices in the Netherlands. Our
      response rate was 53%; i.e., 2,487 of 4,681 questionnaires were returned. The
      Patient Assessment of Chronic Illness Care (PACIC) was used to assess compliance
      with CCM. Quality of life was assessed with the Short-Form 36 Health Survey (SF
      36) and we used the Hospital Anxiety and Depression Scale (HADS) to assess
      depressive symptoms. Multilevel regression models were performed to reveal
      predictors of high CCM compliance. RESULTS: With a mean (SD) of 2.77 (0.86) in
      CVD patients and 2.89 (0.89) in COPD patients (p = 0.002), the PACIC sum score
      was lower than in previous studies conducted in HMOs in the US, but similar to a
      European primary care setting study. The PACIC score was associated with age and
      depressive symptoms in both patient groups. CONCLUSIONS: Younger and less
      depressed patients report higher PACIC scores, indicating that their care better
      aligns to the CCM.

PMID- 22871018
TI  - Comparative molecular developmental aspects of the mammalian- and the avian
      lungs, and the insectan tracheal system by branching morphogenesis: recent
      advances and future directions.
AB  - Gas exchangers fundamentally form by branching morphogenesis (BM), a
      mechanistically profoundly complex process which derives from coherent expression
      and regulation of multiple genes that direct cell-to-cell interactions,
      differentiation, and movements by signaling of various molecular morphogenetic
      cues at specific times and particular places in the developing organ. Coordinated
      expression of growth-instructing factors determines sizes and sites where
      bifurcation occurs, by how much a part elongates before it divides, and the angle
      at which branching occurs. BM is essentially induced by dualities of factors
      where through feedback- or feed forward loops agonists/antagonists are activated
      or repressed. The intricate transactions between the development orchestrating
      molecular factors determine the ultimate phenotype. From the primeval time when
      the transformation of unicellular organisms to multicellular ones occurred by
      systematic accretion of cells, BM has been perpetually conserved. Canonical
      signalling, transcriptional pathways, and other instructive molecular factors are
      commonly employed within and across species, tissues, and stages of development.
      While much still remain to be elucidated and some of what has been reported
      corroborated and reconciled with rest of existing data, notable progress has in
      recent times been made in understanding the mechanism of BM. By identifying and
      characterizing the morphogenetic drivers, and markers and their regulatory
      dynamics, the elemental underpinnings of BM have been more precisely explained.
      Broadening these insights will allow more effective diagnostic and therapeutic
      interventions of developmental abnormalities and pathologies in pre- and
      postnatal lungs. Conservation of the molecular factors which are involved in the
      development of the lung (and other branched organs) is a classic example of
      nature's astuteness in economically utilizing finite resources. Once purposefully
      formed, well-tested and tried ways and means are adopted, preserved, and widely
      used to engineer the most optimal phenotypes. The material and time costs of
      developing utterly new instruments and routines with every drastic biological
      change (e.g. adaptation and speciation) are circumvented. This should assure the
      best possible structures and therefore functions, ensuring survival and
      evolutionary success.

PMID- 22871024
TI  - Correlation of structure and function in the human hotdog-fold enzyme hTHEM4.
AB  - Human THEM4 (hTHEM4) is comprised of a catalytically active hotdog-fold acyl-CoA
      thioesterase domain and an N-terminal domain of unknown fold and function. hTHEM4
      has been linked to Akt1 regulation and cell apoptosis. Herein, we report the X
      ray structure of hHTEM4 bound with undecan-2-one-CoA. Structure guided
      mutagenesis was carried out to confirm the catalytic residues. The N-terminal
      domain is shown to be partially comprised of irregular and flexible secondary
      structure, reminiscent of a protein-binding domain. We demonstrate direct hTHEM4
      Akt1 binding by immunoprecipitation and by inhibition of Akt1 kinase activity,
      thus providing independent evidence that hTHEM4 is an Akt1 negative regulator.

PMID- 22871025
TI  - Case report and brief review of literature on sonographic detection of
      accidentally implanted wooden foreign body causing persistent sinus.
AB  - Despite advances in imaging techniques, the detection of vegetative foreign
      bodies in soft tissues remains a difficult and sometimes even a challenging task.
      Clinical evaluation of such patient may present several months or even years
      after the initial injury and clinician may fail to elicit an antecedent skin
      puncture. X-ray examination will miss radiolucent foreign bodies. A 15-year-old
      boy presented with a draining non-healing sinus at the lateral aspect of his
      right thigh for 9 months. Musculoskeletal ultrasonography was ordered after
      ruling out chronic osteomyelitis to detect possible lesions around the thigh.
      High-frequency linear ultrasonic probe readily detected an elongated foreign body
      within the vastus lateralis muscle. A long piece of wood was confirmed at
      surgery. Non-healing sinus with normal finding in radiograph following old trauma
      should raise the suspicion of implanted radiolucent foreign body/bodies. The role
      of diagnostic ultrasound as a valuable screening tool for the detection of
      foreign body is briefly reviewed.

PMID- 22871026
TI  - Pharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists
      in the treatment of chronic neuropathic pain.
AB  - INTRODUCTION: Chronic neuropathic pain is a debilitating disease caused by a
      lesion of the somatosensory nervous system. The N-methyl-D-aspartate receptor
      (NMDAR) plays an important role in the development of this pain state. Proof of
      efficacy of NMDAR inhibitors in treating neuropathic pain is limited, with the
      non-selective NMDAR antagonist ketamine being most effective. AREAS COVERED: This
      review discusses the efficacy of subanesthetic doses of ketamine in alleviating
      chronic neuropathic pain, and highlights its pharmacokinetics and dynamics. The
      reader will understand under which treatment conditions ketamine is most
      effective, and through which mechanisms ketamine acts to induce long-term pain
      relief. The reader will gain an understanding of ketamine's complex metabolism
      and the role of its metabolite norketamine. Possible future alternatives for
      ketamine are discussed aimed at blockade of the subunit of the NMDAR involved in
      spinal and supraspinal pain pathways (NR2B). EXPERT OPINION: More proof from good
      quality randomized clinical trials on the efficacy of NMDAR inhibitors is
      required. A major advantage of ketamine therapy is the ability of the molecule to
      induce rapid and potent antidepressant effects. This is relevant taken the fact
      that chronic pain and depression are closely linked and are often present in the
      same patient.

PMID- 22871027
TI  - Nanostructured block-random copolymers with tunable magnetic properties.
AB  - It was recently shown that block copolymers (BCPs) produced room-temperature
      ferromagnetic materials (RTFMs) due to their nanoscopic ordering and the
      cylindrical phase yielded the highest coercivity. Here, a series of metal
      containing block-random copolymers composed of an alkyl-functionalized homo block
      (C(16)) and a random block of cobalt complex- (Co) and ferrocene-functionalized
      (Fe) units was synthesized via ring-opening metathesis polymerization. Taking
      advantage of the block-random architecture, the influence of dipolar interactions
      on the magnetic properties of these nanostructured BCP materials was studied by
      varying the molar ratio of the Co units to the Fe units, while maintaining the
      cylindrical phase-separated morphology. DC magnetic measurements, including
      magnetization versus field, zero-field-cooled, and field-cooled, as well as AC
      susceptibility measurements showed that the magnetic properties of the
      nanostructured BCP materials could be easily tuned by diluting the cobalt density
      with Fe units in the cylindrical domains. Decreasing the cobalt density weakened
      the dipolar interactions of the cobalt nanoparticles, leading to the transition
      from a room temperature ferromagnetic (RTF) to a superparamagnetic material.
      These results confirmed that dipolar interactions of the cobalt nanoparticles
      within the phase-separated domains were responsible for the RTF properties of the
      nanostructured BCP materials.

PMID- 22871028
TI  - Severity of menopausal symptoms and cardiovascular and osteoporosis risk factors.
AB  - OBJECTIVES: To assess whether the severity of menopausal symptoms is related to
      increased cardiovascular and osteoporosis risk factors, and to determine whether
      women with more severe menopausal symptoms present a greater percentage of
      osteoporosis disease. METHODS: This was a cross-sectional, descriptive study
      encompassing women aged 45-65 years in the whole Spanish territory. The study
      population sample was collected through random sampling. A total of 10 514 women
      were included. Their sociodemographic, medical history and lifestyle data were
      assessed by means of a survey. The Kupperman Index was used to assess the
      severity of menopausal symptoms. Bone mineral density was measured by the dual X
      ray absorptiometry method. RESULTS: The prevalences of risk factors for
      osteoporosis and cardiovascular disease were 67.6% and 74.8%, respectively. Women
      with a higher intensity of symptoms also had a greater percentage of
      cardiovascular (p < 0.001) and osteoporosis (p < 0.001) risk factors and suffered
      more from osteoporosis disease (p < 0.001). In the logistic regression analysis,
      those variables that contributed to the severity of menopausal symptoms were:
      arterial hypertension (odds ratio (OR) 2.14; 95% confidence interval (CI) 1.49
      2.79; p < 0.001), dyslipidemia (OR 1.94; 95% CI 1.48-2.4; p < 0.001), obesity (OR
      2.23; 95% CI 1.55-2.91; p < 0.001), family history (OR 1.38; 95% CI 1.17-1.59; p
      < 0.01), medication use (OR 1.12; 95% CI 0.52-1.72; p < 0.01) and osteoporosis
      disease (OR 3.71; 95% CI 2.9-4.52; p < 0.001). CONCLUSIONS: Women with more
      severe menopausal symptoms had a greater prevalence of cardiovascular and
      osteoporosis disease risk factors and suffered more from osteoporosis disease
      compared to those who had milder or no menopausal symptoms.

PMID- 22871030
TI  - Stereocontrolled total synthesis of (-)-englerin A.
AB  - The total synthesis of (-)-englerin A, a potent and selective inhibitor of renal
      cancer cell lines, is described. The key feature includes the stereocontrolled
      construction of the cyclopentane structure by taking advantage of a base-promoted
      epoxynitrile cyclization.

PMID- 22871031
TI  - DNA fragmentation status in patients with necrozoospermia.
AB  - The aim of this study was to determine if a relationship exists between the
      levels of sperm DNA fragmentation and necrospermia in infertile men. Semen
      samples obtained from 70 men consulting for infertility evaluation were analyzed
      according to World Health Organization (WHO) guidelines. Patients were subdivided
      into three groups according to the percentage of necrotic spermatozoa:
      normozoospermia (<30%; n = 20), moderate necrozoospermia (50-80%; n = 30), and
      severe necrozoospermia (>80%; n = 20). DNA fragmentation was detected by the
      terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin
      nick-end labeling (TUNEL) assay. The sperm DNA fragmentation index (DFI) was 9.28
      +/- 2.98% in patients with a normal level of necrotic spermatozoa, 20.25 +/-
      3.21% in patients with moderate necrozoospermia, and 35.31 +/- 5.25% in patients
      with severe necrozoospermia. There was a statistically significant increase of
      DNA fragmentation in the necrozoospermic group (P < 0.01). A strong correlation
      was found between the degree of necrozoospermia and sperm DNA fragmentation. We
      concluded that patients with necrozoospermia showed a high level of DNA
      fragmentation compared to normozoospermic men. Severe necrozoospermia (>80%) is a
      predictive factor for increased sperm DNA damage.

PMID- 22871029
TI  - Towards a model of postglacial biogeography in shallow marine species along the
      Patagonian Province: lessons from the limpet Nacella magellanica (Gmelin, 1791).
AB  - BACKGROUND: Patagonia extends for more than 84,000 km of irregular coasts is an
      area especially apt to evaluate how historic and contemporary processes influence
      the distribution and connectivity of shallow marine benthic organisms. The true
      limpet Nacella magellanica has a wide distribution in this province and
      represents a suitable model to infer the Quaternary glacial legacy on marine
      benthic organisms. This species inhabits ice-free rocky ecosystems, has a narrow
      bathymetric range and consequently should have been severely affected by
      recurrent glacial cycles during the Quaternary. We performed phylogeographic and
      demographic analyses of N. magellanica from 14 localities along its distribution
      in Pacific Patagonia, Atlantic Patagonia, and the Falkland/Malvinas Islands.
      RESULTS: Mitochondrial (COI) DNA analyses of 357 individuals of N. magellanica
      revealed an absence of genetic differentiation in the species with a single
      genetic unit along Pacific Patagonia. However, we detected significant genetic
      differences among three main groups named Pacific Patagonia, Atlantic Patagonia
      and Falkland/Malvinas Islands. Migration rate estimations indicated asymmetrical
      gene flow, primarily from Pacific Patagonia to Atlantic Patagonia (Nem=2.21) and
      the Falkland/Malvinas Islands (Nem=16.6). Demographic reconstruction in Pacific
      Patagonia suggests a recent recolonization process (< 10 ka) supported by
      neutrality tests, mismatch distribution and the median-joining haplotype
      genealogy. CONCLUSIONS: Absence of genetic structure, a single dominant
      haplotype, lack of correlation between geographic and genetic distance, high
      estimated migration rates and the signal of recent demographic growth represent a
      large body of evidence supporting the hypothesis of rapid postglacial expansion
      in this species in Pacific Patagonia. This expansion could have been sustained by
      larval dispersal following the main current system in this area. Lower levels of
      genetic diversity in inland sea areas suggest that fjords and channels represent
      the areas most recently colonized by the species. Hence recolonization seems to
      follow a west to east direction to areas that were progressively deglaciated.
      Significant genetic differences among Pacific, Atlantic and Falkland/Malvinas
      Islands populations may be also explained through disparities in their respective
      glaciological and geological histories. The Falkland/Malvinas Islands, more than
      representing a glacial refugium for the species, seems to constitute a sink area
      considering the strong asymmetric gene flow detected from Pacific to Atlantic
      sectors. These results suggest that historical and contemporary processes
      represent the main factors shaping the modern biogeography of most shallow marine
      benthic invertebrates inhabiting the Patagonian Province.

PMID- 22871032
TI  - Field comparison of OraQuick ADVANCE Rapid HIV-1/2 antibody test and two blood
      based rapid HIV antibody tests in Zambia.
AB  - BACKGROUND: Zambia's national HIV testing algorithm specifies use of two rapid
      blood based antibody assays, DetermineHIV-1/2 (Inverness Medical) and if positive
      then Uni-Gold Recombigen HIV-1/2 (Trinity Biotech). Little is known about the
      performance of oral fluid based HIV testing in Zambia. The aims of this study are
      two-fold: 1) to compare the diagnostic accuracy (sensitivity and specificity)
      under field conditions of the OraQuick ADVANCE Rapid HIV-1/2 (OraSure
      Technologies, Inc.) to two blood-based rapid antibody tests currently in use in
      the Zambia National Algorithm, and 2) to perform a cost analysis of large-scale
      field testing employing the OraQuick. METHODS: This was a operational
      retrospective research of HIV testing and questionnaire data collected in 2010 as
      part of the ZAMSTAR (Zambia South Africa TB and AIDS reduction) study. Randomly
      sampled individuals in twelve communities were tested consecutively with OraQuick
      test using oral fluid versus two blood-based rapid HIV tests, Determine and Uni
      Gold. A cost analysis of four algorithms from health systems perspective were
      performed: 1) Determine and if positive, then Uni-Gold (Determine/Uni-Gold);
      based on current algorithm, 2) Determine and if positive, then OraQuick
      (Determine/OraQuick), 3) OraQuick and if positive, then Determine
      (OraQuick/Determine), 4) OraQuick and if positive, then Uni-Gold (OraQuick/Uni
      Gold). This information was then used to construct a model using a hypothetical
      population of 5,000 persons with varying prevalence of HIV infection from 1-30%.
      RESULTS: 4,458 participants received both a Determine and OraQuick test. The
      sensitivity and specificity of the OraQuick test were 98.7 (95%CI, 97.5-99.4) and
      99.8 (95%CI, 99.6-99.9), respectively when compared to HIV positive serostatus.
      The average unit costs per algorithm were US$3.76, US$4.03, US$7.35, and US$7.67
      for Determine/Uni-Gold, Determine/OraQuick, OraQuick/Determine, and OraQuick/Uni
      Gold, respectively, for an HIV prevalence of 15%. CONCLUSIONS: An alternative HIV
      testing algorithm could include OraQuick test which had a high sensitivity and
      specificity. The current Determine/Uni-Gold testing algorithm is the least
      expensive when compared to Determine/OraQuick, OraQuick/Determine, and
      OraQuick/Uni-Gold in the Zambian setting. From our field experience, oral fluid
      based testing offers many advantages over blood-based testing, especially with
      self testing on the horizon.

PMID- 22871033
TI  - Specific and cooperative interactions between oximes and PAMAM dendrimers as
      demonstrated by (1)H NMR study.
AB  - Oximes are important in the treatment of organophosphate (OP) poisoning, but have
      limited biological half-lives. Complexing these drugs with a macromolecule, such
      as a dendrimer, could improve their pharmacokinetics. The present study
      investigates the intermolecular interactions that drive the complexation of oxime
      based drug molecules with fifth generation poly(amidoamine) (PAMAM) dendrimers.
      We performed steady-state binding studies of two molecules, pralidoxime and
      obidoxime, employing multiple NMR methods, including 1D titration, (1)H-(1)H 2D
      spectroscopy (COSY, NOESY), and (1)H diffusion-ordered spectroscopy (DOSY).
      Several important insights were gained in understanding the host-guest
      interactions occurring between the drug molecules and the polymer. First, the
      guest molecules bind to the dendrimer macromolecule through a specific
      interaction rather than through random, hydrophobic encapsulation. Second, this
      specificity is driven primarily by the electrostatic or H-bond interaction of the
      oxime at a dendrimer amine site. Also, the average strength for each drug and
      dendrimer interaction is affected by the surface modification of the polymer.
      Third, individual binding events between oximes and a dendrimer have a negative
      cooperative effect on subsequent oxime binding. In summary, this report provides
      a novel perspective important for designing host systems for drug delivery. 

PMID- 22871034
TI  - Inflammation associated anemia and ferritin as disease markers in SLE.
AB  - INTRODUCTION: In a recent screening to detect biomarkers in systemic lupus
      erythematosus (SLE), expression of the iron storage protein, ferritin, was
      increased. Given that proteins that regulate the storage, transfer and release of
      iron play an important role in inflammation, this study aims to determine the
      serum and urine levels of ferritin and of the iron transfer protein, transferrin,
      in lupus patients and to correlate these levels with disease activity,
      inflammatory cytokine levels and markers of anemia. METHODS: A protein array was
      utilized to measure ferritin expression in the urine and serum of SLE patients
      and healthy controls. To confirm these results as well as the role of the iron
      transfer pathway in SLE, ELISAs were performed to measure ferritin and
      transferrin levels in inactive or active SLE patients and healthy controls. The
      relationship between ferritin/transferrin levels and inflammatory markers and
      anemia was next analyzed. RESULTS: Protein array results showed elevated ferritin
      levels in the serum and urine of lupus patients as compared to controls, which
      were further validated by ELISA. Increased ferritin levels correlated with
      measures of disease activity and anemia as well as inflammatory cytokine titers.
      Though active SLE patients had elevated urine transferrin, serum transferrin was
      reduced. CONCLUSION: Urine ferritin and transferrin levels are elevated
      significantly in SLE patients and correlate with disease activity, bolstering
      previous reports. Most importantly, these changes correlated with the
      inflammatory state of the patients and anemia of chronic disease. Taken together,
      altered iron handling, inflammation and anemia of chronic disease constitute an
      ominous triad in SLE.

PMID- 22871035
TI  - Anti-obesity effects of Boussingaulti gracilis Miers var. pseudobaselloides
      Bailey via activation of AMP-activated protein kinase in 3T3-L1 cells.
AB  - In a previous study, we demonstrated the anti-obesity and hypolipidemic effects
      of Boussingaulti gracilis Miers var. pseudobaselloides Bailey in high-fat diet
      induced obese rats. The present study investigated the molecular mechanisms by
      which B. gracilis Miers var. pseudobaselloides Bailey ethanol extract (BGE)
      conferred antidifferentiation and anti-adipogenic effects in the 3T3-L1
      preadipocyte differentiation model. BGE treatment significantly and dose
      dependently suppressed lipid accumulation and down-regulated the expression of
      major transcription factors involved in adipogenesis, such as peroxisome
      proliferator-activated receptor-gamma, CCAAT/enhancer binding protein alpha,
      sterol regulatory element-binding proteins, and their target genes. It is
      important that treatment with BGE increased phosphorylation of AMP-activated
      protein kinase (AMPK), which is one of the rate-limiting enzymes in the fatty
      acid synthesis pathway, and its direct downstream protein, acetyl-coenzyme A
      carboxylase. These results suggest that BGE may exert anti-adipogenic effects
      through regulation of AMPK activity and expression of genes involved in
      lipogenesis.

PMID- 22871036
TI  - Functional analysis of the interferon-stimulated response element of porcine
      circovirus type 2 and its role during viral replication in vitro and in vivo.
AB  - BACKGROUND: Porcine circovirus type 2 (PCV2) is associated with post-weaning
      multi-systemic wasting syndrome (PMWS) in young weaned pigs. Immune stimulation
      was found to activate the replication of PCV2 and exacerbate the clinical outcome
      of the infection. Proper amount of interferon-alpha (IFN-alpha) is able to
      enhance PCV2 infection and production in Porcine kidney-15 (PK-15) cells when
      administered after inoculation. METHODS: In the present study, luciferase
      reporter assays, construction of mutant viruses, Analysis the replication
      efficiency and the response to IFN-alpha treatment in PK-15 cells and animal
      experiments were carried out to analyze the function of interferon-stimulated
      response element (ISRE) of PCV2 and its role during viral replication in vitro
      and in vivo. RESULTS: A functional viral ISRE sequence, 5'-CTGAAAACGAAAGA-3', was
      identified in Rep gene promoter (Prep) of PCV2. PCV2 Prep is composed of two mini
      promoters, the proximal one span the sequence +1 to -106, containing an ISRE
      while the distal mini promoter is composed of three tandem GC box like sites
      locate at -85 to -194. It was demonstrated that viral ISRE is necessary for
      porcine IFN-alpha initiated luciferase expression enhancement and it plays an
      important role in affecting the replication efficiency of PCV2 in vivo and in
      vitro. CONCLUSIONS: These findings provide a theoretical basis for the Phenomenon
      of immunostimulation is able to enhance PCV2 infection, and improve the
      understanding of the complicated mechanisms involved in the host and pathogen
      interactions of PCV2.

PMID- 22871037
TI  - Hypolimnetic oxygen depletion in eutrophic lakes.
AB  - The oxygen-consuming processes in the hypolimnia of freshwater lakes leading to
      deep-water anoxia are still not well understood, thereby constraining suitable
      management concepts. This study presents data obtained from 11 eutrophic lakes
      and suggests a model describing the consumption of dissolved oxygen (O(2)) in the
      hypolimnia of eutrophic lakes as a result of only two fundamental processes: O(2)
      is consumed (i) by settled organic material at the sediment surface and (ii) by
      reduced substances diffusing from the sediment. Apart from a lake's productivity,
      its benthic O(2) consumption depends on the O(2) concentration in the water
      overlying the sediment and the molecular O(2) diffusion to the sediment. On the
      basis of observational evidence of long-term monitoring data from 11 eutrophic
      lakes, we found that the areal hypolimnetic mineralization rate ranging from 0.47
      to 1.31 g of O(2) m(-2) d(-1) (average 0.90 +/- 0.30) is a function of (i) a
      benthic flux of reduced substances (0.37 +/- 0.12 g of O(2) m(-2) d(-1)) and (ii)
      an O(2) consumption which linearly increases with the mean hypolimnion thickness
      (z(H)) up to ~25 m. This model has important implications for predicting and
      interpreting the response of lakes and reservoirs to restoration measures.

PMID- 22871038
TI  - 2D self-assembly of fused oligothiophenes: molecular control of morphology.
AB  - We report the synthesis and properties of two pi-functional heteroaromatic
      tetracarboxylic acids (isomeric tetrathienoanthracene derivatives 2-TTATA and 3
      TTATA) and their self-assembly on highly oriented pyrolytic graphite. Using
      scanning tunneling microscopy at the liquid-solid interface we show how slight
      geometric differences between the two isomers (position of sulfur in the
      molecule) lead to dramatic changes in monolayer structure. While 3-TTATA self
      assembles exclusively in a highly ordered porous network via dimeric R(2)(2)(8)
      hydrogen-bonding connection (synthon), 2-TTATA is polymorphic, forming a less
      ordered porous network via R(2)(2)(8) synthons as well as a close-packed network
      via rare tetrameric R(4)(4)(16) synthons. Density functional theory calculations
      show that the self-assembly direction is governed by the angle between the
      carboxylic groups and secondary interactions with sulfur atoms.

PMID- 22871039
TI  - Studies on the binding modes of Lassa nucleoprotein complexed with m7GpppG and
      dTTP by molecular dynamic simulations and free energy calculations.
AB  - Lassa virus can cause dreadful human hemorrhagic disease, for which there is no
      effective therapy. A recent study points out that the amino (N)-terminal domain
      of Lassa virus nucleoprotein (NP) plays an important role in viral RNA synthesis
      and firstly solved the X-ray crystal structures of NP complexed with the capped
      Deoxythymidine triphosphate (dTTP) analog, but the binding mode of m7GpppG to the
      N domain of NP, which is required for viral RNA transcription, has not been
      studied. In this study, molecular dynamics (MD) simulations have been carried out
      to investigate the characters of dTTP binding to two forms of NP, i.e. the NP
      without the C domain and the full-length NP model, using two different force
      fields, ff03 and ff99SB, respectively. Our calculated results show that the
      truncated model is reasonable and can replace the full protein model in the
      following MD simulations, and that ff99SB combined with the general AMBER force
      field is more suitable for sampling the structure of small molecule NP complex.
      From the comparisons of stability of hydrogen bonds between small molecule and
      protein in the dTTP and Uridine 5'-Triphosphate complexes, one finds that the
      stable hydrogen bonds between the second phosphate group of small molecules and
      two residues, Thr178 and Arg323, are critical for cap analogs binding to the N
      domain of NP. Additionally, docking method combined with MD simulations have been
      applied to predict the binding mode of m7GpppG to NP; and the hydrogen bond
      analysis and the binding free energy decomposition method (MM/GBSA) are conducted
      to study the interactions in the putative binding mode. The calculated results
      are expected to provide guidance for drug development.

PMID- 22871041
TI  - Short case report: 'Speaking in tongues'--foreign accent syndrome.
AB  - Foreign accent syndrome is a rare dysprosody in which pronunciation of a
      patient's speech is perceived by same-language listeners as sounding foreign.
      Sixty cases have been described between 1941 and 2009. It is commonly associated
      with an acquired brain injury (vascular insult/head injury), but also with
      psychogenic illness and has been described in two cases as a developmental
      problem. Here we describe a case secondary to a minor electrocution associated
      with no evidence of structural brain injury on imaging.

PMID- 22871040
TI  - The mammalian PYHIN gene family: phylogeny, evolution and expression.
AB  - BACKGROUND: Proteins of the mammalian PYHIN (IFI200/HIN-200) family are involved
      in defence against infection through recognition of foreign DNA. The family
      member absent in melanoma 2 (AIM2) binds cytosolic DNA via its HIN domain and
      initiates inflammasome formation via its pyrin domain. AIM2 lies within a cluster
      of related genes, many of which are uncharacterised in mouse. To better
      understand the evolution, orthology and function of these genes, we have
      documented the range of PYHIN genes present in representative mammalian species,
      and undertaken phylogenetic and expression analyses. RESULTS: No PYHIN genes are
      evident in non-mammals or monotremes, with a single member found in each of three
      marsupial genomes. Placental mammals show variable family expansions, from one
      gene in cow to four in human and 14 in mouse. A single HIN domain appears to have
      evolved in the common ancestor of marsupials and placental mammals, and
      duplicated to give rise to three distinct forms (HIN-A, -B and -C) in the
      placental mammal ancestor. Phylogenetic analyses showed that AIM2 HIN-C and pyrin
      domains clearly diverge from the rest of the family, and it is the only PYHIN
      protein with orthology across many species. Interestingly, although AIM2 is
      important in defence against some bacteria and viruses in mice, AIM2 is a
      pseudogene in cow, sheep, llama, dolphin, dog and elephant. The other 13 mouse
      genes have arisen by duplication and rearrangement within the lineage, which has
      allowed some diversification in expression patterns. CONCLUSIONS: The role of
      AIM2 in forming the inflammasome is relatively well understood, but molecular
      interactions of other PYHIN proteins involved in defence against foreign DNA
      remain to be defined. The non-AIM2 PYHIN protein sequences are very distinct from
      AIM2, suggesting they vary in effector mechanism in response to foreign DNA, and
      may bind different DNA structures. The PYHIN family has highly varied gene
      composition between mammalian species due to lineage-specific duplication and
      loss, which probably indicates different adaptations for fighting infectious
      disease. Non-genomic DNA can indicate infection, or a mutagenic threat. We
      hypothesise that defence of the genome against endogenous retroelements has been
      an additional evolutionary driver for PYHIN proteins.

PMID- 22871042
TI  - Pharmacokinetics and toxicity of antimuscarinic drugs for overactive bladder
      treatment in females.
AB  - INTRODUCTION: Antimuscarinics (AMs) are the mainstay of pharmacological treatment
      of overactive bladder (OAB), a symptom complex defined by the presence of urinary
      urgency, usually associated with frequency and nocturia, with or without urgency
      urinary incontinence. The AMs used to treat OAB differ in their pharmacological
      profiles, which may affect their potential for causing adverse effects (AEs).
      AREAS COVERED: The present article aims to review the literature about
      pharmacokinetics (PK) of the different AMs used in the treatment of OAB.
      Furthermore, the AEs related to the use of these drugs and their incidence are
      presented. This systematic review is based on material searched and obtained via
      Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse
      events, pharmacokinetics, tolerability" in combination with "darifenacin,
      fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine,
      and trospium." EXPERT OPINION: Antimuscarinics are the first-line pharmacological
      treatment for OAB. Despite the development of new molecules that improve their
      efficacy/safety profile, there are some drugs that are pharmacokinetically more
      appropriate to be prescribed in specific populations such as patients with
      neurological disease or the elderly. Moreover, research should be encouraged in
      evaluating antimuscarinics in conjunction with other drugs such as estrogens or
      beta-agonists. The identification of prognostic criteria for pharmacological
      therapy would be helpful.

PMID- 22871043
TI  - Individual differences, cultural differences, and dialectic conflict description
      and resolution.
AB  - Previous research suggests that members of East Asian cultures show a greater
      preference for dialectical thinking than do Westerners. This paper attempts to
      account for these differences in cognition using individual difference variables
      that may explain variation in performance both within and across cultures.
      Especially, we propose that the abovementioned cultural differences are rooted in
      a greater fear of isolation (FOI) in East Asians than in Westerners. To support
      this hypothesis, in Experiment 1, we manipulated FOI in American participants
      before having them resolve two conflicts: an interpersonal conflict and a
      conflict between an individual and an institution. We found that the Americans
      among whom a high level of FOI had been induced were more likely to look for a
      dialectical resolution than those among whom a low level had been prompted. The
      relationship between conflict resolution and FOI was further investigated in
      Experiment 2, in which FOI was not manipulated. The results indicated that
      Koreans had higher chronic FOI on average than did the Americans. Compared to the
      Americans, the Koreans were more likely to resolve the interpersonal conflict
      dialectically, but did not show the same bias in resolving the person-institution
      conflict. The differences in the preference for dialectical resolution between
      FOI conditions in Experiment 1 and cultural groups in Experiment 2 were mediated
      by FOI. These findings bolster previous research on FOI in showing that chronic
      levels of FOI are positively related to both preference for dialectical sentences
      and sensitivity to context. They provide clearer insight into how differences in
      FOI affect attention and thereby higher-level reasoning such as dialectic
      description and conflict resolution. 

PMID- 22871045
TI  - Revisiting current "barefoot doctors" in border areas of China: system of
      services, financial issue and clinical practice prior to introducing integrated
      management of childhood illness (IMCI).
AB  - BACKGROUND: Under-5-years child mortality remains high in rural China. Integrated
      management of childhood illness (IMCI) was introduced to China in 1998, but only
      a few rural areas have been included. This study aimed at assessing the current
      situation of the health system of rural health care and evaluating the clinical
      competency of village doctors in management of childhood illnesses prior to
      implementing IMCI programme in remote border rural areas. METHODS: The study was
      carried out in the border areas of Puer prefecture of Yunnan province. There were
      182 village doctors in the list of the health bureau in these border areas. Of
      these, 154 (84.6%) were recruited into the study. The local health system
      components were investigated using a qualitative approach and analyzed with
      triangulation of information from different sources. The clinical component was
      assessed objectively and quantitatively presented using descriptive statistics.
      RESULTS: The study found that the New Rural Cooperative Medical Scheme (NRCMS)
      coordinated the health insurance system and the provider service through 3 tiers:
      village doctor, township and county hospitals. The 30 RMB per person per year
      premium did not cover the referral cost, and thereby decreased the number of
      referrals. In contrast to available treatment facilities and drug supply, the
      level of basic medical education of village doctors and township doctors was low.
      Discontent among village doctors was common, especially concerning low rates of
      return from the service, exceptions being procedures such as injections, which in
      fact may create moral hazards to the patients. Direct observation on the
      assessment and management of paediatric patients by village doctors revealed
      inadequate history taking and physical examination, inability to detect
      potentially serious complications, overprescription of injection and antibiotics,
      and underprescription of oral rehydration salts and poor quality of counseling.
      CONCLUSION: There is a need to improve health finance and clinical competency of
      the village doctors in the study area.

PMID- 22871046
TI  - Is non-invasive ventilation the best ventilatory support for 'do not intubate'
      patients?

PMID- 22871044
TI  - Eat-me: autophagy, phagocytosis, and reactive oxygen species signaling.
AB  - SIGNIFICANCE: Phagocytosis is required for the clearance of dying cells. The
      subsequent regulation of inflammatory responses by phagocytic cells is mediated
      by both innate and adaptive immune responses. Autophagy, an evolutionarily
      ancient process of lysosomal self-digestion of organelles, protein aggregates,
      apoptotic corpses, and cytosolic pathogens, has only recently become appreciated
      for its dynamic relationship with phagocytosis, including newly discovered
      autophagic-phagocytosis "hybrid" processes such as microtubule-associated protein
      1 light chain 3-associated phagocytosis (LAP). RECENT ADVANCES: Signal
      transduction by reactive oxygen species (ROS) plays a critical role in the
      modulation of autophagy, phagocytosis, and LAP, and serves as both a link and an
      additional layer of regulation between these processes. Furthermore, specific
      targets for oxidation by ROS molecules have recently begun to become identified
      in each of these processes, as have "shared" proteins that facilitate the
      successful completion of both autophagy and phagocytosis. High mobility group box
      1 is at the crossroads of autophagy, phagocytosis, and oxidative stress. CRITICAL
      ISSUES: In this review, we discuss the most recent findings that link elements of
      autophagy and phagocytosis, specifically through redox-dependent signal
      transduction. These interconnected cellular processes are placed in the context
      of cell death and immunity in both health and disease. FUTURE DIRECTIONS: Given
      the broad roles that autophagy, phagocytosis, and ROS signaling play in human
      health, disease, and the maintenance of cellular and organismal homeostatic
      balance, it is important to delineate intersections between these pathways and
      uncover targets for potential therapeutic intervention in the setting of
      autoimmune and inflammatory diseases.

PMID- 22871047
TI  - Promoter methylation status of HIN-1 associated with outcomes of ovarian clear
      cell adenocarcinoma.
AB  - BACKGROUND: This study is to analyze promoter methylation of various tumor
      suppressor genes in different types of ovarian carcinoma and to identify
      potential therapeutic targets of ovarian clear cell adenocarcinoma (OCCA).
      MATERIALS AND METHODS: The promoter methylation statuses of 40 genes in primary
      ovarian carcinomas including 47 clear- and 63 non-clear-cell type tissues, 6 OCCA
      cell lines, 29 benign ovarian endometriotic cysts, and 31 normal controls were
      analyzed by methylation-specific multiplex ligation-dependent probe amplification
      (MS-MLPA). The MS-MLPA results were correlated with clinicopathological features
      and outcomes of 47 OCCA patients. Functions of the target genes were further
      explored by Western Blot Analysis, apoptosis assay, and caspase-3/7 activity
      analysis. RESULTS: Frequencies of methylated RASSF1A, CDH13, CACNA1A, HIN-1, and
      sFRP5 genes in OCCA tissues were significantly higher than those in non-OCCA
      cancerous tissues and benign endometriotic cysts. The expected OS for patients
      with methylated promoters of HIN-1 was significantly worse than those for
      patients without methylated HIN-1 (30% vs. 62%, p = 0.002). The HIN-1 gene was
      over-expressed in ES2 cells, a significant reduction in cell growth and induction
      of apoptosis, and increasing paclitaxel sensitivity by reducing phosphorylation
      of Akt were observed. CONCLUSIONS: Methylation of HIN-1 promoter is a novel
      epigenetic biomarker associated with poor outcomes in OCCA patients. Ectopic
      expression of the HIN-1 gene increased paclitaxel sensitivity which is partly
      through Akt pathway.

PMID- 22871048
TI  - Clinical efficacy and safety of a pharmacopial polyherbal Unani formulation in
      pityriasis versicolor: a comparative randomized single-blind study.
AB  - BACKGROUND: Pityriasis versicolor (PV) is a common superficial fungal infection
      of skin caused by the fungus, Malassezia furfur. It can occur at any age but
      occurs mainly during adolescence and typically presents with hypopigmented or
      hyperpigmented scaling plaques, generally on the trunk and upper arms. It often
      poses a therapeutic challenge. In the Unani system of medicine, many herbal drugs
      are used empirically for its treatment. OBJECTIVES: The objective of this study
      was to evaluate safety and efficacy of a topical Polyherbal Unani formulation in
      the management of PV on scientific parameters. DESIGN: This was a randomized,
      single-blind, standard controlled study. LOCATION: This study was performed in
      the Dermatology Outpatient Department, National Institute of Unani Medicine,
      Bangalore, India. SUBJECTS AND INTERVENTIONS: Forty-six (46) patients with PV
      were included in the study after taking informed consents and were randomly
      allocated to test and control groups. In the test group, a polyherbal formulation
      was advised for topical application while in the control group, sodium
      thiosulphate lotion (20%) was advised locally for a duration of 1 month. The
      assessment of the severity of PV and efficacy of treatment in both groups was
      carried out using the Total Sign and Symptom Score (TSSS) scale. Data were
      analyzed with the Instat Graph pad. RESULTS: The mean+/-standard error of the
      mean (SEM) scores of TSSS in the test group were 7.7+/-1.174 and 0.9+/-0.7881
      before and after treatment, respectively, while it was 6.9+/-0.8756 and 1.2+/
      0.7888 in the control group before and after treatment, respectively. Mean+/-SEM
      of TSSS of both groups was found to be significantly lowered (p<0.001) after
      treatment when compared with mean+/-SEM of TSSS before treatment. However, the
      polyherbal formulation showed precedence over the standard drug by exhibiting
      comparatively quicker response. Furthermore, no unpleasant side-effects were
      observed in the test group during and after the study. CONCLUSIONS: This study
      concluded that polyherbal Unani formulation is safe, effective, and superior to
      standard drug in the treatment of PV.

PMID- 22871049
TI  - Visualisation in imaging mass spectrometry using the minimum noise fraction
      transform.
AB  - BACKGROUND: Imaging Mass Spectrometry (IMS) provides a means to measure the
      spatial distribution of biochemical features on the surface of a sectioned tissue
      sample. IMS datasets are typically huge and visualisation and subsequent analysis
      can be challenging. Principal component analysis (PCA) is one popular data
      reduction technique that has been used and we propose another; the minimum noise
      fraction (MNF) transform which is popular in remote sensing. FINDINGS: The MNF
      transform is able to extract spatially coherent information from IMS data. The
      MNF transform is implemented through an R-package which is available together
      with example data from http://staff.scm.uws.edu.au/~glenn/?#Software.
      CONCLUSIONS: In our example, the MNF transform was able to find additional images
      of interest. The extracted information forms a useful basis for subsequent
      analyses.

PMID- 22871050
TI  - Overview of ultrasound usage trends in orthopedic and sports physiotherapy.
AB  - BACKGROUND: The purpose of this study is to examine current beliefs about the
      use, the clinical importance, the theoretical fundamentals and the utilization
      criteria of therapeutic ultrasound (TUS) among physical therapists on the
      clinical practice in orthopedic and sports physiotherapy in Brazil. METHODS: A
      brief survey was developed based on previous studies and was sent to 55 physical
      therapists with advanced competency in orthopedics and sports physiotherapy. The
      questions addressed general topics about the professional profile and ultrasound
      usage and dosage. RESULTS: Our data show the wide availability and frequent use
      of TUS in this sample of physical therapists. TUS is used in distinct
      musculoskeletal injuries and/or disorders in both acute and chronic conditions.
      Muscles, tendons and ligaments represented the major structures where TUS is
      used. Questions on the basic theory of TUS demonstrated a lack of knowledge of
      the ultrasound physiological effects as well as its interaction with biological
      tissues and TUS absolute contraindication. CONCLUSION: A Brazilian profile about
      the US usage and dosage in orthopedic and sports physiotherapy is presented and
      highlights the need for a continuous upgrading process and further research into
      its effects.

PMID- 22871052
TI  - Handedness enantioselection of carbon nanotubes using helical assemblies of
      flavin mononucleotide.
AB  - In order to truly unlock advanced applications of single-walled carbon nanotubes
      (SWNTs), one needs to separate them according to both chirality and handedness.
      Here we show that the chiral D-ribityl phosphate chain of flavin mononucleotide
      (FMN) induces a right-handed helix that enriches the left-handed SWNTs for all
      suspended (n,m) species. Such enantioselectivity stems from the sp(3)
      hybridization of the N atom anchoring the sugar moiety to the flavin ring. This
      produces two FMN conformations (syn and anti) analogous to DNA. Electrostatic
      interactions between the neighboring uracil moiety and the 2'-OH group of the
      side chain provide greater stability to the anti-FMN conformation that leads to a
      right-handed FMN helix. The right-handed twist that the FMN helix imposes to the
      underlying nanotube, similar to "Indian burn", causes diameter dilation of only
      the left-handed SWNTs, whose improved intermolecular interactions with the
      overlaying FMN helix, impart enantioselection.

PMID- 22871053
TI  - The effects of fructose-1,6-diphosphate on haemodynamic parameters and survival
      in a rodent model of propranolol and verapamil poisoning.
AB  - BACKGROUND: Fructose-1,6-diphosphate (FDP) is a metabolite in the glycolytic
      pathway created from glucose. Exogenously administered FDP increases the yield of
      ATP from anaerobic glycolysis. FDP reduces ischaemic tissue area in
      experimentally-induced cerebral and myocardial infarction and improves
      haemodynamics post-cardiac bypass. We hypothesised that FDP improves
      haemodynamics in propranolol and verapamil poisoning. METHOD: Anesthetized Wistar
      rats were instrumented to record BP, heart rate (HR), cardiac output (CO) and QRS
      duration. Propranolol or verapamil were infused continually. When BP dropped by
      50%, propranolol-poisoned rats received one of 10% FDP125 mg/kg or 10% FDP250
      mg/kg loading dose over 20 minutes followed by infusion 20 mg/kg/h. Verapamil
      poisoned rats received the higher dosing regimen of FDP250. Controls received
      comparable volumes of 10% glucose. Haemodynamic time-points were compared for FDP
      to control by unpaired t-test or Mann-Whitney test as appropriate (p <  0.05).
      Survival was assessed using Kaplan-Meier survival analysis. RESULTS: FDP-treated
      animals survived significantly longer than glucose-treated controls at both doses
      in propranolol poisoning and in verapamil-poisoning. In propranolol poisoning,
      FDP250-treated animals showed a statistically significant increase in BP.
      However, there was no significant difference in cardiac output at this dose.
      There were also no significant differences in any haemodynamic parameters
      compared to control at the lower FDP dose in propranolol poisoning or in
      verapamil poisoning. CONCLUSION: FDP improved survival for both toxicants with an
      improvement in haemodynamics at the higher dose in propranolol poisoning. Future
      research could examine the efficacy of FDP in other beta-blocker and calcium
      channel-blocker poisoning as well as in concert with established inotropic
      therapies in drug-induced cardiovascular collapse.

PMID- 22871056
TI  - Addressing disparities in maternal health care in Pakistan: gender, class and
      exclusion.
AB  - BACKGROUND: After more than two decades of the Safe Motherhood Initiative and
      Millennium Development Goals aimed at reducing maternal mortality, women continue
      to die in childbirth at unacceptably high rates in Pakistan. While an extensive
      literature describes various programmatic strategies, it neglects the rigorous
      analysis of the reasons these strategies have been unsuccessful, especially for
      women living at the economic and social margins of society. A critical gap in
      current knowledge is a detailed understanding of the root causes of disparities
      in maternal health care, and in particular, how gender and class influence policy
      formulation and the design and delivery of maternal health care services. Taking
      Pakistan as a case study, this research builds upon two distinct yet interlinked
      conceptual approaches to understanding the phenomenon of inequity in access to
      maternal health care: social exclusion and health systems as social institutions.
      METHODS/DESIGN: This four year project consists of two interrelated modules that
      focus on two distinct groups of participants: (1) poor, disadvantaged women and
      men and (2) policy makers, program managers and health service providers. Module
      one will employ critical ethnography to understand the key axes of social
      exclusion as related to gender, class and zaat and how they affect women's
      experiences of using maternal health care. Through health care setting
      observations, interviews and document review, Module two will assess policy
      design and delivery of maternal health services. DISCUSSION: This research will
      provide theoretical advances to enhance understanding of the power dynamics of
      gender and class that may underlie poor women's marginalization from health care
      systems in Pakistan. It will also provide empirical evidence to support
      formulation of maternal health care policies and health care system practices
      aimed at reducing disparities in maternal health care in Pakistan. Lastly, it
      will enhance inter-disciplinary research capacity in the emerging field of social
      exclusion and maternal health and help reduce social inequities and achieve the
      Millennium Development Goal No. 5.

PMID- 22871057
TI  - Disproportionation of bromous acid HOBrO by direct O-transfer and via anhydrides
      O(BrO)2 and BrO-BrO2. An ab initio study of the mechanism of a key step of the
      Belousov-Zhabotinsky oscillating reaction.
AB  - The results are reported of an ab initio study of the thermochemistry and of the
      kinetics of the HOBrO disproportionation reaction 2HOBrO (2) ? HOBr (1) + HBrO(3)
      (3), reaction ( R4' ), in gas phase (MP2(full)/6-311G*) and aqueous solution
      (SMD(MP2(full)/6-311G*)). The reaction energy of bromous acid disproportionation
      is discussed in the context of the coupled reaction system R2-R4 of the FKN
      mechanism of the Belousov-Zhabotinsky reaction and considering the acidities of
      HBr and HOBrO(2). The structures were determined of ten dimeric aggregates 4 of
      bromous acid, (HOBrO)(2), of eight mixed aggregates 5 formed between the products
      of disproportionation, (HOBr)(HOBrO(2)), and of four transition states structures
      6 for disproportionation by direct O-transfer. It was found that the condensation
      of two HOBrO molecules provides facile access to bromous acid anhydride 7,
      O(BrO)(2). A discussion of the potential energy surface of Br(2)O(3) shows that
      O(BrO)(2) is prone to isomerization to the mixed anhydride 8, BrO-BrO(2), and to
      dissociation to 9, BrO, and 10, BrO(2), and their radical pair 11. Hence, three
      possible paths from O(BrO)(2) to the products of disproportionation, HOBr and
      HOBrO(2), are discussed: (1) hydrolysis of O(BrO)(2) along a path that differs
      from its formation, (2) isomerization of O(BrO)(2) to BrO-BrO(2) followed by
      hydrolysis, and (3) O(BrO)(2) dissociation to BrO and BrO(2) and their reactions
      with water. The results of the potential energy surface analysis show that the
      rate-limiting step in the disproportionation of HOBrO consists of the formation
      of the hydrate 12a of bromous acid anhydride 7 via transition state structure
      14a. The computed activation free enthalpy DeltaG(act)(SMD) = 13.6 kcal/mol for
      the process 2.2a -> [14a](?) -> 12a corresponds to the reaction rate constant
      k(4) = 667.5 M(-1) s(-1) and is in very good agreement with experimental
      measurements. The potential energy surface analysis further shows that anhydride
      7 is kinetically and thermodynamically unstable with regard to hydrolysis to HOBr
      and HOBrO(2) via transition state structure 14b. The transition state structure
      14b is much more stable than 14a, and, hence, the formation of the "symmetrical
      anhydride" from bromous acid becomes an irreversible reaction for all practical
      purposes because 7 will instead be hydrolyzed as a "mixed anhydride" to afford
      HOBr and HOBrO(2). The mixed anhydride 8, BrO-BrO(2), does not play a significant
      role in bromous acid disproportionation.

PMID- 22871058
TI  - Furfuraldehyde hydrogenation on titanium oxide-supported platinum nanoparticles
      studied by sum frequency generation vibrational spectroscopy: acid-base catalysis
      explains the molecular origin of strong metal-support interactions.
AB  - This work describes a molecular-level investigation of strong metal-support
      interactions (SMSI) in Pt/TiO(2) catalysts using sum frequency generation (SFG)
      vibrational spectroscopy. This is the first time that SFG has been used to probe
      the highly selective oxide-metal interface during catalytic reaction, and the
      results demonstrate that charge transfer from TiO(2) on a Pt/TiO(2) catalyst
      controls the product distribution of furfuraldehyde hydrogenation by an acid-base
      mechanism. Pt nanoparticles supported on TiO(2) and SiO(2) are used as catalysts
      for furfuraldehyde hydrogenation. As synthesized, the Pt nanoparticles are
      encapsulated in a layer of poly(vinylpyrrolidone) (PVP). The presence of PVP
      prevents interaction of the Pt nanoparticles with their support, so identical
      turnover rates and reaction selectivity is observed regardless of the supporting
      oxide. However, removal of the PVP with UV light results in a 50-fold enhancement
      in the formation of furfuryl alcohol by Pt supported on TiO(2), while no change
      is observed for the kinetics of Pt supported on SiO(2). SFG vibrational
      spectroscopy reveals that a furfuryl-oxy intermediate forms on TiO(2) as a result
      of a charge transfer interaction. This furfuryl-oxy intermediate is a highly
      active and selective precursor to furfuryl alcohol, and spectral analysis shows
      that the Pt/TiO(2) interface is required primarily for H spillover. Density
      functional calculations predict that O-vacancies on the TiO(2) surface activate
      the formation of the furfuryl-oxy intermediate via an electron transfer to
      furfuraldehyde, drawing a strong analogy between SMSI and acid-base catalysis.

PMID- 22871059
TI  - Green tea extract suppresses adiposity and affects the expression of lipid
      metabolism genes in diet-induced obese zebrafish.
AB  - BACKGROUND: Visceral fat accumulation is one of the most important predictors of
      mortality in obese populations. Administration of green tea extract (GTE) can
      reduce body fat and reduce the risk of obesity-related diseases in mammals. In
      this study, we investigated the effects and mechanisms of GTE on adiposity in
      diet-induced obese (DIO) zebrafish. METHODS: Zebrafish at 3.5 to 4.5 months post
      fertilization were allocated to four groups: non-DIO, DIO, DIO + 0.0025%GTE, and
      DIO + 0.0050%GTE. The non-DIO group was fed freshly hatched Artemia once daily (5
      mg cysts/fish daily) for 40 days. Zebrafish in the three DIO groups were fed
      freshly hatched Artemia three times daily (60 mg cysts/fish daily). Zebrafish in
      the DIO + 0.0025%GTE and DIO + 0.0050%GTE groups were exposed to GTE after the
      start of feeding three times daily for 40 days. RESULTS: Three-dimensional
      microcomputed tomography analysis showed that GTE exposure significantly
      decreased the volume of visceral but not subcutaneous fat tissue in DIO
      zebrafish. GTE exposure increased hepatic expression of the lipid catabolism
      genes ACOX1 (acyl-coenzyme A oxidase 1, palmitoyl), ACADM (acyl-coenzyme A
      dehydrogenase, c-4 to c-12 straight chain), and PPARA (peroxisome proliferator
      activated receptor alpha). GTE exposure also significantly decreased the visceral
      fat expression of SOCS3 (suppressor of cytokine signaling 3b) which inhibits
      leptin signaling. CONCLUSIONS: The present results are consistent with those seen
      in mammals treated with GTE, supporting the validity of studying the effects of
      GTE in DIO zebrafish. Our results suggest that GTE exerts beneficial effects on
      adiposity, possibly by altering the expression of lipid catabolism genes and
      SOCS3.

PMID- 22871060
TI  - Oral delivery of doxorubicin using novel polyelectrolyte-stabilized liposomes
      (layersomes).
AB  - The present study explores the potential of polyelectrolyte-coated liposomes for
      improving the oral deliverability of doxorubicin (Dox). As a part of formulation
      strategy, stearyl amine was selected as a formulation component to provide
      positive charge to liposomes, which were subsequently coated with anionic
      poly(acrylic acid)  (PAA) followed by coating of cationic polyallyl amine
      hydrochloride (PAH) in a layer by layer manner and led to the formation of a
      robust structure "layersomes". Optimization of various process variables were
      carried out, and optimized formulation was found to have particle size of 520.4
      +/- 15.0 nm, PDI of 0.312 +/- 0.062, zeta potential of +30.4 +/- 5.32 mV, and
      encapsulation efficiency of 63.4 +/- 4.26%. Layersomes were not only stable in
      simulated gastrointestinal fluids but also presented sustained drug release
      (~35%) as compared to both Dox-liposomes and PAA-Dox-liposomes (~67%), the
      release pattern being Higuchi kinetics. The in vivo pharmacokinetics studies
      revealed about 5.94-fold increase in oral bioavailability of Dox as compared to
      free drug. In vivo antitumor efficacy in a DMBA-induced breast tumor model
      further exhibited significant reduction in the tumor growth as compared to
      control and IV-Dox, while results were comparable to IV-LipoDox. Layersomes also
      exhibited a marked reduction in cardiotoxicity in comparison with IV-doxorubicin
      and IV-LipoDox (marketed formulation), as evidenced by the reduced levels of
      malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine phosphokinase
      (CK-MB) and increased levels of glutathione (GSH) and superoxide dismutase (SOD).
      The reduced cardiotoxicity of layersomes was further confirmed by comparative
      histopathological examination of heart tissue after treatment with various
      formulations. The positive results of the study strengthen our expectation that
      the developed formulation strategy can be fruitfully exploited to improve the
      oral deliverability of poorly bioavailable drugs and can open new vistas for oral
      chemotherapy.

PMID- 22871061
TI  - The constituents of essential oil: antimicrobial and antioxidant activity of
      Micromeria congesta Boiss. & Hausskn. ex Boiss. from East Anatolia.
AB  - The chemical composition, antimicrobial activity, total phenol content, total
      antioxidant activity, and total oxidant status of the essential oil from
      Micromeria congesta Boiss. & Hausskn. ex Boiss. were investigated. Steam
      distillation was used to obtain the essential oil, and the chemical analyses were
      performed by gas chromatography-mass spectrometry. The antimicrobial activity was
      tested by an agar disc diffusion method against the tested microorganisms:
      Bacillus subtilis NRRL B-744, Bacillus cereus NRRL B-3711, Staphylococcus aureus
      ATCC 12598, S. aureus ATCC 25923, S. aureus ATCC 25933, Escherichia coli 0157H7,
      E. coli ATCC25922, Micrococcus luteus NRLL B-4375, Enterococcus faecalis ATCC
      19433, Proteus vulgaris RSKK 96026, and Yersinia enterecolitica RSKK 1501. The
      major compounds found in volatiles of M. congesta were piperitone oxide, linalool
      oxide, veratrole, pulegone, dihydro carvone, naphthalene, iso-menthone, para
      menthone, and cyclohexanone. Compared to that of reference antibiotics, the
      antibacterial activity of the essential oil is considered as significant. Results
      showed that M. congesta has the potential for being used in food and medicine
      depending on its antioxidant and antibacterial activity.

PMID- 22871062
TI  - Sleep duration in elderly obese patients correlated negatively with intake fatty.
AB  - STUDY OBJECTIVES: The purpose of the present study was to evaluate the
      relationship between sleep duration and dietary habits in elderly obese patients
      treated at an institute of cardiology. METHODS: The fifty-eight volunteers were
      elderly patients with obesity (classified as obese according to BMI) of both
      genders, between 60 and 80 years of age. All participants were subjected to
      assessments of food intake, anthropometry, level of physical activity, and
      duration of sleep. RESULTS: The men had significantly greater weight, height, and
      waist circumference than women. Sleep durations were correlated with dietary
      nutrient compositions only in men. We found a negative association between short
      sleep and protein intake (r = -0.43; p = 0.02), short sleep and monounsaturated
      fatty acids intake (r = -0.40; p = 0.03), and short sleep and cholesterol dietary
      intake (r = -0.50; p = 0.01). CONCLUSIONS: We conclude that mainly in men,
      volunteers that had short sleep duration showed a preference for high energy
      density as fatty food, at least in part, may explain the relationship between
      short sleep duration and the development of metabolic abnormalities.

PMID- 22871063
TI  - MWCNT/V2O5 core/shell sponge for high areal capacity and power density Li-ion
      cathodes.
AB  - A multiwall carbon nanotube (MWCNT) sponge network, coated by ALD V(2)O(5),
      presents the key characteristics needed to serve as a high-performance cathode in
      Li-ion batteries, exploiting (1) the highly electron-conductive nature of MWCNT,
      (2) unprecedented uniformity of ALD thin film coatings, and (3) high surface area
      and porosity of the MWCNT sponge material for ion transport. The core/shell
      MWCNT/V(2)O(5) sponge delivers a stable high areal capacity of 816 MUAh/cm(2) for
      2 Li/V(2)O(5) (voltage range 4.0-2.1 V) at 1C rate (1.1 mA/cm(2)), 450 times that
      of a planar V(2)O(5) thin film cathode. At much higher current (50*), the areal
      capacity of 155 MUAh/cm(2) provides a high power density of 21.7 mW/cm(2). The
      compressed sponge nanoarchitecture thus demonstrates exceptional robustness and
      energy-power characteristics for thin film cathode structures for electrochemical
      energy storage.

PMID- 22871064
TI  - Assessment of new cationic porphyrin binding to plasma proteins by planar
      microarray and spectroscopic methods.
AB  - Porphyrins have a unique aromatic structure determining particular photochemical
      properties that make them promising photosensitizers for anticancer therapy.
      Previously, we synthesized a set of artificial porphyrins by modifying side-chain
      functional groups and introducing different metals into the core structure. Here,
      we have performed a comparative study of the binding properties of 29 cationic
      porphyrins with plasma proteins by using microarray and spectroscopic approaches.
      The porphyrins were noncovalently immobilized onto hydrogel-covered glass slides
      and probed to bio-conjugated human and bovine serum albumins, as well as to human
      hemoglobin. The signal detection was carried out at the near-infrared
      fluorescence wavelength (800 nm) that enabled the effect of intrinsic visible
      wavelength fluorescence emitted by the porphyrins tested to be discarded.
      Competition assays on porphyrin microarrays indicated that long-chain fatty acids
      (FAs) (palmitic and stearic acids) decrease porphyrin binding to both serum
      albumin and hemoglobin. The binding affinity of different types of cationic
      porphyrins for plasma proteins was quantitatively assessed in the absence and
      presence of FAs by fluorescent and absorption spectroscopy. Molecular docking
      analysis confirmed results that new porphyrins and long-chain FAs compete for the
      common binding site FA1 in human serum albumin and meso-substituted functional
      groups in porphyrins play major role in the modulation of conformational
      rearrangements of the protein.

PMID- 22871065
TI  - Elevated cardiac troponin in the early post-operative period and mortality
      following ruptured abdominal aortic aneurysm: a retrospective population-based
      cohort study.
AB  - INTRODUCTION: Cardiac complications are potentially life-threatening following
      emergency repair of ruptured abdominal aortic aneurysms (rAAA). Our objectives
      were to describe the incidence, risk factors, cardiac outcomes and mortality
      associated with elevated cardiac-specific troponin (cTnI) following repair of
      rAAA. We hypothesized that early post-operative cTnI elevation (>0.15 mcg/L) in
      rAAA patients would identify a high-risk subgroup for cardiovascular
      complications and adverse outcomes. METHODS: This was a retrospective population
      based cohort study of all referrals for emergency repair of rAAA in central and
      northern Alberta, from 1 January 2002 to 31 December 2009. Demographic, clinical,
      physiologic and laboratory data were extracted, along with cardiac-specific
      investigations and events in the 72 hours following rAAA repair. RESULTS: In
      total, 55% of patients (n = 77/141) had elevated cTnI, of which 12% (n = 9) had
      ST segment elevation, 23% (n = 18) had ST segment depression, 5% (n = 4) had
      other ECG changes, and 61% (n = 47) had no diagnostic ECG changes. Those with
      positive cTnI were more likely to have coronary artery disease (45.5% vs. 23.4%,
      P = 0.01) and higher Acute Physiology and Chronic Health Evaluation (APACHE) II
      scores (24.9 vs. 21.4, n = 0.016). cTnI positive patients were more likely to
      receive vasoactive support (58.4% vs. 14.1%, P < 0.001), had longer intensive
      care unit (ICU) lengths of stay (8 (3 to 11) vs. 4 (2 to 9) days, P = 0.02) and
      higher adjusted in-hospital mortality (40.3% vs. 14.1%; OR 4.23; 95% CI, 1.47 to
      12.1; P = 0.007). CONCLUSIONS: Elevated cTnI early after rAAA repair is an
      independent predictor for post-operative complications and death.

PMID- 22871066
TI  - Vibrational assignment of the ultrafast infrared spectrum of the photoactivatable
      flavoprotein AppA.
AB  - The blue light using flavin (BLUF) domain proteins, such as the transcriptional
      antirepressor AppA, are a novel class of photosensors that bind flavin
      noncovalently in order to sense and respond to high-intensity blue (450 nm)
      light. Importantly, the noncovalently bound flavin chromophore is unable to
      undergo large-scale structural change upon light absorption, and thus there is
      significant interest in understanding how the BLUF protein matrix senses and
      responds to flavin photoexcitation. Light absorption is proposed to result in
      alterations in the hydrogen-bonding network that surrounds the flavin chromophore
      on an ultrafast time scale, and the structural changes caused by photoexcitation
      are being probed by vibrational spectroscopy. Here we report ultrafast time
      resolved infrared spectra of the AppA BLUF domain (AppA(BLUF)) reconstituted with
      isotopes of FAD, specifically [U-(13)C(17)]-FAD, [xylene-(13)C(8)]-FAD, [U
      (15)N(4)]-FAD, and [4-(18)O(1)]-FAD both in solution and bound to AppA(BLUF).
      This allows for unambiguous assignment of ground- and excited-state modes arising
      directly from the flavin. Studies of model compounds and DFT calculations of the
      ground-state vibrational spectra reveal the sensitivity of these modes to their
      environment, indicating they can be used as probes of structural dynamics.

PMID- 22871067
TI  - Practice task design in team sports: representativeness enhanced by increasing
      opportunities for action.
AB  - This study investigated effects of manipulating the number of action
      possibilities in a futsal passing task to understand the representativeness of
      practice tasks designs. Eight male senior futsal players performed a passing task
      in which uncertainty on passing direction for the player in possession of the
      ball was increased in four conditions and compared with passing data from a
      competitive match. Performance during a passing task and competitive futsal
      performance was compared using ball speed and passing accuracy data. Ball speed
      data were analysed by approximate entropy (ApEn) to capture their regularity in
      each of the four conditions and during competitive performance. Significantly
      high levels of regularity were observed in predetermined passes in comparison
      with emergent passes (i.e., passes with high number of possibilities for action).
      Similar results for ball speed regularity were observed between practice tasks
      with a high number of possibilities for action (i.e., emergent passes) and
      competitive performance. Similar results were observed for passing accuracy in
      practice tasks with a high number of possibilities for action compared to
      competitive performance. Increases in the number of action possibilities during
      practice improved action fidelity of tasks in relation to competitive
      performance.

PMID- 22871068
TI  - Stroke or coronary artery disease prediction from mean platelet volume in
      patients with type 2 diabetes mellitus.
AB  - The aim of this study was to determine the association of mean platelet volume
      (MPV) with the development of stroke or coronary artery disease (CAD) in diabetes
      mellitus (DM). MPV was analyzed in 200 Korean patients with DM. The primary
      endpoint was composite of ischemic stroke/CAD events. The mean MPV was 7.6 +/-
      0.8 fl. There were 14 ischemic stroke events and 8 CAD events during a mean of
      28.4 months of follow-up. The Kaplan-Meier analysis revealed that the higher
      tertile MPV group (>=7.9 fl) had a significantly higher stroke/CAD rate compared
      to the lower tertile MPV group (<=7.3 fl) (29.9% vs. 2.8%, log-rank: p < 0.001).
      Higher MPV was an independent predictor of stroke/CAD risk after adjusting for 10
      year risk >=10%, hypertension, dyslipidemia, and previous stroke or transient
      ischemic attack history (hazard ratio: 11.92, 95% confidence interval 2.68-52.92,
      p = 0.001) in the Cox proportional hazard analysis. When the MPV cut-off level
      was set to 7.95 fl using the receiver operating characteristic curve, the
      sensitivity was 91% and the specificity was 80% for differentiating between the
      group with stroke/CAD and the group without stroke/CAD. This value was more
      useful in patients with hypertension. The results of this study show that MPV is
      a predictive marker for stroke/CAD; its predictive power for stroke/CAD is
      independent of age, gender, hypertension, and hemoglobin A1C. 

PMID- 22871070
TI  - Treatment-independent miRNA signature in blood of Wilms tumor patients.
AB  - BACKGROUND: Blood-born miRNA signatures have recently been reported for various
      tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients
      prior and after preoperative chemotherapy according to SIOP protocol 2001.
      RESULTS: We did not find a significant difference between miRNA signature of both
      groups. However both, Wilms tumor patients prior and after chemotherapy showed a
      miRNA signature different from healthy controls. The signature of Wilms tumor
      patients prior to chemotherapy showed an accuracy of 97.5% and of patients after
      chemotherapy an accuracy of 97.0%, each as compared to healthy controls.
      CONCLUSION: Our results provide evidence for a blood-born Wilms tumor miRNA
      signature largely independent of four weeks preoperative chemotherapy treatment.

PMID- 22871069
TI  - Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role
      of cytochrome P450 isozymes.
AB  - INTRODUCTION: Alcohol consumption, which is highly prevalent in HIV-infected
      individuals, poses serious concerns in terms of rate of acquisition of HIV-1
      infection, HIV-1 replication, response to highly active antiretroviral therapy
      (HAART) and AIDS/neuroAIDS progression. However, little is known about the
      mechanistic pathways by which alcohol exerts these effects, especially with
      respect to HIV-1 replication and the patient's response to HAART. AREAS COVERED:
      In this review, the authors discuss the effects of alcohol consumption on HIV-1
      pathogenesis and its effect on HAART. They also describe the role of cytochrome
      P450 2E1 (CYP2E1) in alcohol-mediated oxidative stress and toxicity, and the role
      of CYP3A4 in the metabolism of drugs used in HAART (i.e., protease inhibitors
      (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI)). Based on the
      most recent findings the authors discuss the role of CYP2E1 in alcohol-mediated
      oxidative stress in monocytes/macrophages and astrocytes, as well as the role of
      CYP3A4 in alcohol-PI interactions leading to altered metabolism of PI in these
      cells. EXPERT OPINION: The authors propose that alcohol and PI/NNRTI interact
      synergistically in monocytes/macrophages and astrocytes through the CYP pathway
      leading to an increase in oxidative stress and a decrease in response to HAART.
      Ultimately, this exacerbates HIV-1 pathogenesis and neuroAIDS.

PMID- 22871071
TI  - Impact of community tracer teams on treatment outcomes among tuberculosis
      patients in South Africa.
AB  - BACKGROUND: Tuberculosis (TB) indicators in South Africa currently remain well
      below global targets. In 2008, the National Tuberculosis Program (NTP)
      implemented a community mobilization program in all nine provinces to trace TB
      patients that had missed a treatment or clinic visit. Implementation sites were
      selected by TB program managers and teams liaised with health facilities to
      identify patients for tracing activities. The objective of this analysis was to
      assess the impact of the TB Tracer Project on treatment outcomes among TB
      patients. METHODS: The study population included all smear positive TB patients
      registered in the Electronic TB Registry from Quarter 1 2007-Quarter 1 2009 in
      South Africa. Subdistricts were used as the unit of analysis, with each
      designated as either tracer (standard TB program plus tracer project) or non
      tracer (standard TB program only). Mixed linear regression models were utilized
      to calculate the percent quarterly change in treatment outcomes and to compare
      changes in treatment outcomes from Quarter 1 2007 to Quarter 1 2009 between
      tracer and non-tracer subdistricts. RESULTS: For all provinces combined, the
      percent quarterly change decreased significantly for default treatment outcomes
      among tracer subdistricts (-0.031%; p < 0.001) and increased significantly for
      successful treatment outcomes among tracer subdistricts (0.003%; p = 0.03). A
      significant decrease in the proportion of patient default was observed for all
      provinces combined over the time period comparing tracer and non-tracer
      subdistricts (p = 0.02). Examination in stratified models revealed the results
      were not consistent across all provinces; significant differences were observed
      between tracer and non-tracer subdistricts over time in five of nine provinces
      for treatment default. CONCLUSIONS: Community mobilization of teams to trace TB
      patients that missed a clinic appointment or treatment dose may be an effective
      strategy to mitigate default rates and improve treatment outcomes. Additional
      information is necessary to identify best practices and elucidate discrepancies
      across provinces; these findings will help guide the NTP in optimizing the
      adoption of tracing activities for TB control.

PMID- 22871072
TI  - Copper(II) binding by dissolved organic matter: importance of the copper-to
      dissolved organic matter ratio and implications for the biotic ligand model.
AB  - The ratio of copper to dissolved organic matter (DOM) is known to affect the
      strength of copper binding by DOM, but previous methods to determine the Cu(2+)
      DOM binding strength have generally not measured binding constants over the same
      Cu:DOM ratios. In this study, we used a competitive ligand exchange-solid-phase
      extraction (CLE-SPE) method to determine conditional stability constants for
      Cu(2+)-DOM binding at pH 6.6 and 0.01 M ionic strength over a range of Cu:DOM
      ratios that bridge the detection windows of copper-ion-selective electrode and
      voltammetry measurements. As the Cu:DOM ratio increased from 0.0005 to 0.1 mg of
      Cu/mg of DOM, the measured conditional binding constant ((c)K(CuDOM)) decreased
      from 10(11.5) to 10(5.6) M(-1). A comparison of the binding constants measured by
      CLE-SPE with those measured by copper-ion-selective electrode and voltammetry
      demonstrates that the Cu:DOM ratio is an important factor controlling Cu(2+)-DOM
      binding strength even for DOM isolates of different types and different sources
      and for whole water samples. The results were modeled with Visual MINTEQ and
      compared to results from the biotic ligand model (BLM). The BLM was found to over
      estimate Cu(2+) at low total copper concentrations and under-estimate Cu(2+) at
      high total copper concentrations.

PMID- 22871073
TI  - Specially designed palate prosthesis reconstitutes speech in amyotrophic lateral
      sclerosis.

PMID- 22871074
TI  - Functional improvement in mouse models of familial amyotrophic lateral sclerosis
      by PEGylated insulin-like growth factor I treatment depends on disease severity.
AB  - Insulin-like growth factor I (IGF-I) has been successfully tested in the SOD1
      G93A mouse model of familial amyotrophic lateral sclerosis (ALS) and proposed for
      clinical treatment. However, beneficial effects required gene therapy or
      intrathecal application. Circumventing the dosing issues we recently found that
      polyethylene glycol (PEG) modified IGF-I (PEG-IGF-I) modulated neuromuscular
      function after systemic application, and protected against disease progression in
      a motor neuron disease model. Here we investigated its effects in two SOD1-G93A
      mouse lines, the G1L with a milder and the G1H with a more severe phenotype.
      Results showed that in G1L mice, PEG-IGF-I treatment significantly improved
      muscle force, motor coordination and animal survival. In contrast, treatment of
      G1H mice with PEG-IGF-I or IGF-I even at high doses did not beneficially affect
      survival or functional outcomes despite increased signalling in brain and spinal
      cord by both agents. In conclusion, the data point towards further investigation
      of the therapeutic potential of PEG-IGF-I in ALS patients with less severe
      clinical phenotypes.

PMID- 22871075
TI  - Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: results
      from five prospective cohort studies.
AB  - Animal and pathological studies suggest that inflammation may contribute to
      amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti
      inflammatory drugs (NSAIDs) might be protective. However, there are no
      prospective data on the relation between NSAID use and ALS risk in humans. The
      relation between NSAID use and ALS risk was explored in five large prospective
      cohort studies (the Nurses' Health Study, the Health Professionals Follow-up
      Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort
      Study, and the National Institutes of Health - AARP Diet and Health Study).
      Detailed NSAID information was sought from 780,000 participants, 708 of whom
      developed ALS during follow-up. Cox proportional hazards models were used within
      each cohort and cohort-specific estimates were pooled with random effects models.
      Results showed that neither non-aspirin NSAID use, nor aspirin use was associated
      with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI
      0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of
      NSAID use in years and frequency of NSAID use were not associated with ALS risk
      overall. In conclusion, the results do not support an overall effect of NSAIDs on
      ALS risk, but because NSAIDs have heterogeneous effects, a role of individual
      compounds cannot be excluded.

PMID- 22871076
TI  - Season and weather patterns at time of birth in amyotrophic lateral sclerosis.
AB  - Studies in the northern hemisphere suggest that the numbers of amyotrophic
      lateral sclerosis (ALS) births vary depending on the season of the year. We
      wished to determine if a southern hemisphere study would show the same seasonal
      changes, and whether particular weather conditions were associated with the
      numbers of ALS births. Birth data from a case-control study of Australian
      residents were used to relate monthly birth rates of ALS to the seasons and
      weather conditions. The results were compared with previous studies in Japan,
      Sweden and Switzerland. Four hundred and ninety-one Australian sporadic ALS
      patients and 629 controls (partners, friends, and community volunteers) completed
      a self-reported questionnaire that included dates of birth. Australian ALS birth
      rates increased between late summer and early winter, and decreased between mid
      winter and early summer. Similar patterns were seen in Japan and Sweden. Monthly
      average humidity correlated positively with the numbers of ALS births in
      Australia, Sweden, and Japan. In conclusion, seasonal differences in ALS birth
      rates in the southern hemisphere are similar to those in two out of three
      northern hemisphere countries. Early life factors related to weather conditions,
      such as increased humidity leading to more infectious diseases and allergens,
      need to be further investigated in ALS.

PMID- 22871077
TI  - Eating-derived pleasure in amyotrophic lateral sclerosis as a predictor of non
      oral feeding.
AB  - Our objective was to examine the pleasure derived from eating in patients with
      advanced ALS and how this affects advice to have a gastrostomy. Patients with
      advanced ALS completed a visual analogue scale indicating the pleasure they
      derived from eating. Data were also collected on the severity of swallow using
      the Hillel scale, the independent feeding status, and on whether gastrostomy was
      accepted or not. The findings from 38 consecutive patients indicate that pleasure
      derived from eating is a powerful indicator of a person's acceptance of
      gastrostomy. In conclusion, the study showed that a simple analogue scale is
      quick and practical in a clinical setting even in severely compromised people
      with ALS and that the eating pleasure score was a strong predictor of the final
      decision to accept gastrostomy placement (p = 12.2 = 10(-4)).

PMID- 22871078
TI  - Using transcutaneous carbon dioxide monitor (TOSCA 500) to detect respiratory
      failure in patients with amyotrophic lateral sclerosis: a validation study.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition,
      respiratory failure being the commonest cause of death. Quality of life and
      survival can be improved by supporting respiratory function with non-invasive
      ventilation. Transcutaneous carbon dioxide monitoring is a non-invasive method of
      measuring arterial carbon dioxide levels enabling simple and efficient screening
      for respiratory failure. The aim of this study was to validate the accuracy of
      carbon dioxide level recorded transcutaneously with a TOSCA 500 monitor. It is a
      prospective, observational study of 40 consecutive patients with ALS, recruited
      from a specialist ALS clinic. The partial pressure of carbon dioxide (PCO(2)) in
      each patient was determined by both transcutaneous monitoring and by an
      arterialized ear lobe capillary blood sample. The carbon dioxide (CO(2)) levels
      obtained with these two methods were compared by Bland-Altman analysis. The
      results showed that the mean difference between arterialized and transcutaneous
      readings was - 0.083 kPa (SD 0.318). The Bland-Altman limits of agreement ranged
      from 0.553 to - 0.719 kPa. The difference was < 0.5 kPa in 90% of the recordings.
      Four of the 40 measurements had a difference of > 0.5 kPa, with a maximum
      recorded difference of 0.95 kPa. In conclusion, non-invasive carbon dioxide
      monitoring using a TOSCA monitor is a useful clinical tool in neurology practice.
      Users should be aware of the possibility of occasional inaccurate readings. A
      clinically unexpected or incompatible reading should be verified with a blood gas
      analysis, especially when a decision to provide ventilatory support is required.

PMID- 22871079
TI  - Speech therapy and communication device: impact on quality of life and mood in
      patients with amyotrophic lateral sclerosis.
AB  - Dysarthria has a drastic impact on the quality of life of ALS patients. Most
      patients suffering from dysarthria are offered speech therapy. Communication
      devices are prescribed less frequently. In the present study we investigated the
      impact of these therapeutic arrangements on quality of life in ALS patients.
      Thirty-eight ALS patients with dysarthria or anarthria, who underwent speech
      therapy and/or used communication devices answered three standardized
      questionnaires (Beck Depression Inventory - II (BDI), SF-36 Health Survey
      questionnaire (SF-36) and ALS Functional Rating Scale-revised (ALSFRS-R)) and
      were further interviewed about their experience with and benefit of speech
      therapy and communication devices. Most of the patients described a high impact
      of the communication device on their quality of life while the influence of
      speech therapy was rated less. By multiple regression analysis we confirmed an
      independent positive effect of communication device use on depression and
      psychological distress. In conclusion, communication systems improve or at least
      stabilize quality of life and mood in dysarthric ALS patients, and should be
      provided early in the disease course.

PMID- 22871080
TI  - Aggressiveness, sexuality, and obsessiveness in late stages of ALS patients and
      their effects on caregivers.
AB  - Clinical experience has shown an increase of behavioural and mood symptoms,
      especially in the areas of aggressiveness, sexuality and obsessiveness, during
      the late stages of ALS. The lack of conclusive data concerning these symptoms
      prompted us to assess the psychological aspects of ALS patients in advanced
      stages of the disease. Moreover, we evaluated the personality of their caregivers
      in order to analyse the relationship between the pair. For these purposes, we
      studied 10 patients with ALS in late stages (tracheostomized for 36 months) and
      their caregivers using a questionnaire specifically elaborated for patients'
      communication limits. To assess the state of anxiety and depression of both
      patients and caregivers, we used the Hospital Anxiety and Depression Scale
      (HADS). To investigate caregivers' personality, we administered the Big Five
      Questionnaire (BFQ). Data showed a trend of aggression and high level of
      obsessiveness in ALS patients, associated with several clinical characteristics.
      High levels of anxiety emerged in both patients and caregivers. Regarding BFQ,
      caregivers obtained higher scores in the dimension of Conscientiousness and very
      low scores in Extraversion and Emotional Stability. In conclusion, the study
      showed a potential and considerable effect of the long duration of ALS on
      patients' personality and caregivers' distress.

PMID- 22871081
TI  - Likelihood of acute coronary syndrome in emergency department chest pain patients
      varies with time of presentation.
AB  - BACKGROUND: There is a circadian and circaseptal (weekly) variation in the onset
      of acute coronary syndrome (ACS). The aim of this study was to elucidate whether
      the likelihood of ACS among emergency department (ED) chest pain patients varies
      with the time of presentation. METHODS: All patients presenting to the Lund ED at
      Skane University Hospital with chest pain or discomfort during 2006 and 2007 were
      retrospectively included. Age, sex, arrival time at the ED and discharge diagnose
      (ACS or not) were obtained from the electronic medical records. RESULTS: There
      was a clear but moderate circadian variation in the likelihood of ACS among
      presenting chest pain patients, the likelihood between 8 and 10 am being almost
      twice as high as between 6 and 8 pm. This was mainly explained by a variation in
      the ACS likelihood in females and patients under 65 years, with no significant
      variation in males and patients over 65 years. There was no significant
      circaseptal variation in the ACS likelihood. CONCLUSIONS: Our results indicate
      that there is a circadian variation in the likelihood of ACS among ED chest pain
      patients, and suggest that physicians should consider the time of presentation to
      the ED when determining the likelihood of ACS.

PMID- 22871082
TI  - Optimization of self nanoemulsifying drug delivery system for poorly water
      soluble drug using response surface methodology.
AB  - There is an increasing interest on self-nanoemulsifying drug delivery system
      (SNEDDS) for oral delivery of poorly water-soluble drugs. However, development of
      SNEDDS is often driven by empiric, pseudo-ternary diagrams and solubility of
      drugs, and it is lacking a systematic approach for evaluating impact of
      excipients on the performance of formulations as well as the fate of drug. The
      aim of this study was to rationalize the SNEDDS development procedure and to get
      a better understanding on the role of excipients on the SNEDDS. The formulations
      consist of soybean oil or rapeseed oil, Cremophor((r)) RH40, MaisineTM 35-1 and
      ethanol. Response surface methodology (RSM) was used in the development of
      SNEDDS. Significant advantages of RSM were found in reducing the work load and
      determining the impact of excipients on formulation characteristics. The most
      significant factor in influencing droplet size was the co-surfactant MaisineTM 35
      1, the droplet size increased with increasing concentration of MaisineTM 35-1. It
      suggests that MaisineTM 35-1 has double functions in the SNEDDS; it functions as
      co-surfactant to improve the emulsification of oil, meanwhile it also works as
      the oil phase and results in larger droplets. A significant reduction in droplet
      size was interestingly observed when fenofibrate was loaded in the vehicles,
      probably due to the surface activity of fenofibrate, promoting the self
      emulsifying process. It was evident that drug precipitation during lipolysis was
      not affected by the level of co-solvent ethanol in the formulation, while it had
      pronounced impact on drug solubilization during the initial dispersion stage.

PMID- 22871083
TI  - Derivation of a pediatric growth curve for inferior vena caval diameter in
      healthy pediatric patients: brief report of initial curve development.
AB  - BACKGROUND: A validated tool has long been sought to provide clinicians with a
      uniform and accurate method to assess hydration status in the pediatric emergency
      medicine population. Outpatient clinicians use CDC height- and weight-based
      curves for the assessment of physical development. In hospital, daily weights
      provide objective data; however, these are usually not available at
      presentation.One of the most promising techniques for the rapid assessment of
      volume is ultrasound (US) to obtain an indexed inferior vena cava diameter
      (IVCDi); as previously described. Prior studies have focused on IVCDi in
      dehydrated patients and have shown that it provides accurate estimates of right
      atrial pressure and volume status. The objective of this study is to derive an
      IVC growth curve in healthy pediatric patients. METHODS: Prospective cohort
      design enrolled healthy children between the ages of 4 weeks and 20 years.
      Patients presenting with fever, illnesses, or diagnoses known to affect the
      volume will be excluded. All eligible patients under 21, who have provided self
      or parental written consent, will undergo a brief ultrasound to obtain transverse
      and long images of both the IVC and the aorta; all scans will be digitally saved.
      Image quality will be subjectively rated as poor, fair, or good based on wall
      clarity. Poor quality images will be recorded but may be omitted from our
      analysis. Five clinicians completed a 1-h introduction to IVC-US and ten
      supervised scans prior to enrollment. Still images will be measured in order to
      determine IVCDi in both transverse and longitudinal planes. To assess inter-rater
      reliability, in 10% of cases, two clinicians will complete scans. All study scans
      will be over-read by a fellowship-trained sonologist.IVCDi will be plotted
      independently as functions of age, gender, BMI, and aortic diameter. Within each
      group, means with means or medians with 95% CIs will be calculated. Following uni
      and bivariate analyses and assessment for colinearity, a variety of parametric
      and nonparametric regression procedures will be conducted. The smoothed curves
      will be approximated using a modified LMS estimation procedure. RESULTS: Data for
      the initial curve derivation includes 25 patients ranging from 13 months to 20
      years (mean 102 months or 8.5 years). Sixty-five percent of patients were
      enrolled from the ED, while 35% were enrolled from well-child clinic visits. When
      evaluating the size of IVC as a function of time linear growth, increasing size
      was found to proportionately increase with age of patient in months. CONCLUSIONS:
      Data suggest a linear correlation between IVC size and age. Such data, when
      plotted as a new growth curve, may allow clinicians to plot a patient's
      sonographic measurements in order to assess hydration health.

PMID- 22871084
TI  - Integrative transcriptome analysis suggest processing of a subset of long non
      coding RNAs to small RNAs.
AB  - BACKGROUND: The availability of sequencing technology has enabled understanding
      of transcriptomes through genome-wide approaches including RNA-sequencing.
      Contrary to the previous assumption that large tracts of the eukaryotic genomes
      are not transcriptionally active, recent evidence from transcriptome sequencing
      approaches have revealed pervasive transcription in many genomes of higher
      eukaryotes. Many of these loci encode transcripts that have no obvious protein
      coding potential and are designated as non-coding RNA (ncRNA). Non-coding RNAs
      are classified empirically as small and long non-coding RNAs based on the size of
      the functional RNAs. Each of these classes is further classified into functional
      subclasses. Although microRNAs (miRNA), one of the major subclass of ncRNAs, have
      been extensively studied for their roles in regulation of gene expression and
      involvement in a large number of patho-physiological processes, the functions of
      a large proportion of long non-coding RNAs (lncRNA) still remains elusive. We
      hypothesized that some lncRNAs could potentially be processed to small RNA and
      thus could have a dual regulatory output. RESULTS: Integration of large-scale
      independent experimental datasets in public domain revealed that certain well
      studied lncRNAs harbor small RNA clusters. Expression analysis of the small RNA
      clusters in different tissue and cell types reveal that they are differentially
      regulated suggesting a regulated biogenesis mechanism. CONCLUSIONS: Our analysis
      suggests existence of a potentially novel pathway for lncRNA processing into
      small RNAs. Expression analysis, further suggests that this pathway is regulated.
      We argue that this evidence supports our hypothesis, though limitations of the
      datasets and analysis cannot completely rule out alternate possibilities. Further
      in-depth experimental verification of the observation could potentially reveal a
      novel pathway for biogenesis.

PMID- 22871085
TI  - Prognostic value of hepatic venous pressure gradient in patients with compensated
      chronic hepatitis C-related cirrhosis.
AB  - BACKGROUND AND AIM: Hepatic venous pressure gradient (HVPG) is the main predictor
      of clinical decompensation in cirrhotic patients with compensated disease of any
      etiology without varices. However, the predictive factors of decompensation are
      not so well known in patients with hepatitis C-related compensated cirrhosis, in
      whom etiology-based therapy is difficult. The aim of this study was to identify
      predictors of decompensation in patients with compensated chronic hepatitis C
      (CHC)-related cirrhosis with and without esophageal varices (Baveno stages 1 and
      2). METHODS: The study population was a cohort of 145 of such consecutive
      patients who received hepatic hemodynamic study. All patients were similarly
      followed every 6 months. Through multivariate Cox regression and bootstrap
      analyses, a prognostic index (PI) was developed and tested in an external cohort
      (n = 38). RESULTS: Forty-two patients (29%) suffered a first decompensation
      episode after a median follow-up of 27 months (2-110). Cox regression analysis
      identified HVPG (hazard ratio (HR) 1.11; 95% confidence interval (CI): 1.05-1.17)
      and albumin (HR 0.42; 95% CI: 0.22-0.82) as independent predictors of
      decompensation. Bootstrapping confirmed that HVPG (95% CI: 1.05-1.18) and albumin
      (95% CI: 0.12-0.74) were the most robust predictive variables. Using a cut-off
      level of 2.5, the PI [4 + (0.11 * HVPG - 0.8 * albumin)] was able to distinguish
      two populations of patients with very different risks of decompensation in both
      the exploratory and validation cohorts. A time-dependent ROC curve identified
      HVPG as the best predictive variable. CONCLUSION: HVPG and albumin are
      independent predictors of clinical decompensation in patients with compensated
      CHC-related cirrhosis irrespective of the existence of varices.

PMID- 22871086
TI  - A retrospective, pooled data analysis of the safety of pegaptanib sodium in the
      treatment of age-related macular degeneration in subjects with or without
      diabetes mellitus.
AB  - BACKGROUND: To evaluate the safety of pegaptanib sodium 0.3 mg intravitreal
      injection in the treatment of neovascular age-related macular degeneration in
      subjects with or without diabetes mellitus. METHODS: A pooled, retrospective,
      analysis was conducted of data from 9 sponsor-administered, randomized, open
      label trials. Subjects who received pegaptanib by randomization or change in dose
      assignment, crossover design, or protocol amendment, were included. Reports of
      endophthalmitis, increased intraocular pressure, retinal injury, intraocular
      hemorrhage, traumatic cataract, hypersensitivity reactions, stroke, myocardial
      infarction, and other arterial thromboembolic events defined by the Antiplatelet
      Trialists' Collaboration were identified by Medical Dictionary for Regulatory
      Activities preferred terms. Adverse events were summarized from the first
      injection to 42 days after the last injection. The incidence of adverse events
      was stratified by the presence/absence of diabetes. RESULTS: Of 1,586 subjects
      enrolled, 165 (10.4%) had a history of diabetes mellitus and 1,421 (89.6%) did
      not. The 2 populations were similar at baseline. Based on the comparison of
      prespecified ocular, hypersensitivity, and Antiplatelet Trialists' Collaboration
      event terms, the safety review did not identify any notable differences between
      the 2 populations. CONCLUSIONS: This retrospective analysis found no increased
      safety risk resulting from treatment with pegaptanib 0.3 mg in individuals with
      neovascular age-related macular degeneration and concomitant diabetes mellitus.

PMID- 22871087
TI  - Review of patient-reported outcome measures in chronic hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C (CHC) and its treatment are associated with a
      variety of patient-reported symptoms and impacts. Some CHC symptoms and impacts
      may be difficult to evaluate through objective clinical testing, and more easily
      measured through patient self-report. This literature review identified concepts
      raised by CHC patients related to symptoms, impacts, and treatment effects, and
      evaluated integration of these concepts within patient-reported outcome (PRO)
      measures. The goal of this work was to provide recommendations for incorporation
      of PRO measurement of concepts that are relevant to the CHC experience into CHC
      clinical trial design. METHODS: A three-tiered literature search was conducted.
      This included searches on concepts of importance, PRO measures used in clinical
      trials, and existing PRO measures. The PRO Concept Search focused on reviewing
      issues raised by CHC patients about CHC symptoms, disease impact, and treatment
      effects. The CHC Trials with PRO Endpoints Search reviewed clinical trials with
      PRO endpoints to assess differences between treatments over time. The PRO Measure
      Search reviewed existing PRO measures associated with the concepts of interest.
      RESULTS: This multi-tiered approach identified five key concepts of interest:
      depression/anxiety, fatigue, flu-like symptoms, cognitive function, insomnia.
      Comparing these five concepts of interest to the PRO measures in published CHC
      clinical trials showed that, while treatment of CHC may decrease health-related
      quality of life in a number of mental and physical domains, the PRO measures that
      were utilized in published clinical trials inadequately covered the concepts of
      interest. Further review of 18 existing PRO measures of the concepts of interest
      showed only four of the 18 were validated in CHC populations. CONCLUSIONS: This
      review identified several gaps in the literature regarding assessment of symptoms
      and outcomes reported as important by CHC patients. Further research is needed to
      ensure that CHC clinical trials evaluate concepts that are important to patients
      and include measures that have evidence supporting content validity, reliability,
      construct validity, and responsiveness.

PMID- 22871088
TI  - Structural elucidation of rapid solution-mediated phase transitions in
      pharmaceutical solids using in situ synchrotron SAXS/WAXS.
AB  - In situ elucidation of kinetics of solution-mediated phase transformations using
      direct structural determination has been achieved using synchrotron SAXS/WAXS
      radiation. Using theophylline as a model drug with known phase transformation
      from anhydrate to monohydrate form in aqueous conditions within a few minutes,
      the kinetics of the structural transition were resolved at the second scale, and
      the results achieved agreed well with those determined using indirect approaches
      such as Raman spectroscopy. The recrystallization of the monohydrate in situ (due
      to its lower solubility) from dissolved anhydrate solution (higher solubility) is
      demonstrated directly, highlighting a major issue for such compounds in
      application. The technique has the additional benefit of having the potential to
      identify intermediate structures which are not readily achievable with in situ
      spectroscopic techniques, as well as being amenable to high throughput
      approaches.

PMID- 22871089
TI  - Anti-inflammatory and neuroactive properties of selected fruit extracts.
AB  - Epidemiological evidence supports inverse associations between fruit and
      vegetable intake and incidence of cardiovascular disease and neurodegeneration.
      Dietary botanicals with salient health benefits include berries and leafy
      vegetables. Molecular pharmacology research has ascribed these benefits primarily
      to phenolic constituents and antioxidant activity. The current investigation
      sought to eluicidate pharmacologic activity of two novel preparations of berry
      and spinach extracts in vitro. Blueberry and cranberry exhibited the greatest
      antioxidant activity. In a dose-dependent manner, a proprietary mixture of
      cranberry and blueberry extracts inhibited inhibitor of kappaB kinase beta, a
      central node in inflammatory signal transduction. A proprietary mixture of
      blueberry, strawberry, and spinach extracts inhibited prolyl endopeptidase, a
      regulator of central neuropeptide stability and an emerging therapeutic target in
      neurology and psychiatry. These results indicate specific molecular targets of
      blended dietary plants with potential relevance to inflammation and neurological
      health.

PMID- 22871091
TI  - Localized partial oxidation of acetic acid at the dual perimeter sites of the
      Au/TiO2 catalyst-formation of gold ketenylidene.
AB  - Chemisorbed acetate species derived from the adsorption of acetic acid have been
      oxidized on a nano-Au/TiO(2) (~3 nm diameter Au) catalyst at 400 K in the
      presence of O(2)(g). It was found that partial oxidation occurs to produce gold
      ketenylidene species, Au(2)?C?C?O. The reactive acetate intermediates are bound
      at the TiO(2) perimeter sites of the supported Au/TiO(2) catalyst. The
      ketenylidene species is identified by its measured characteristic stretching
      frequency nu(CO) = 2040 cm(-1) and by (13)C and (18)O isotopic substitution
      comparing to calculated frequencies found from density functional theory. The
      involvement of dual catalytic Ti(4+) and Au perimeter sites is postulated on the
      basis of the absence of reaction on a similar nano-Au/SiO(2) catalyst. This
      observation excludes low coordination number Au sites as being active alone in
      the reaction. Upon raising the temperature to 473 K, the production of CO(2) and
      H(2)O is observed as both acetate and ketenylidene species are further oxidized
      by O(2)(g). The results show that partial oxidation of adsorbed acetate to
      adsorbed ketenylidyne can be cleanly carried out over Au/TiO(2) catalysts by
      control of temperature.

PMID- 22871090
TI  - Endotoxemia and mortality prediction in ICU and other settings: underlying risk
      and co-detection of gram negative bacteremia are confounders.
AB  - INTRODUCTION: The interdependence between endotoxemia, gram negative (GN)
      bacteremia and mortality has been extensively studied. Underlying patient risk
      and GN bacteremia types are possible confounders of the relationship. METHODS:
      Published studies with >= 10 patients in either ICU or non-ICU settings,
      endotoxemia detection by limulus assay, reporting mortality proportions and >= 1
      GN bacteremia were included. Summary odds ratios (OR) for mortality were derived
      across all studies by meta-analysis for the following contrasts: sub-groups with
      either endotoxemia (group three), GN bacteremia (group two) or both (group one)
      each versus the group with neither detected (group four; reference group). The
      mortality proportion for group four is the proxy measure of study level risk
      within L'Abbe plots. RESULTS: Thirty-five studies were found. Among nine studies
      in an ICU setting, the OR for mortality was borderline (OR <2) or non
      significantly increased for groups two (GN bacteremia alone) and three
      (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co
      detected) each versus patient group four (neither endotoxemia nor GN bacteremia
      detected). The ORs were markedly higher for group one versus group four (OR 6.9;
      95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The
      distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among
      groups one versus two are significantly unequal. CONCLUSIONS: The co-detection of
      GN bacteremia and endotoxemia is predictive of increased mortality risk versus
      the detection of neither but only in studies undertaken in a non-ICU setting.
      Variation in GN bacteremia species types and underlying risk are likely
      unrecognized confounders in the individual studies.

PMID- 22871093
TI  - Synthesis of novel mannoside glycolipid conjugates for inhibition of HIV-1 trans
      infection.
AB  - Mannose-binding lectins, such as dendritic cell-specific ICAM-3-grabbing non
      integrin (DC-SIGN), are expressed at the surface of human dendritic cells (DCs)
      that capture and transmit human immunodeficiency virus type-1 (HIV-1) to CD4(+)
      cells. With the goal of reducing viral trans-infection by targeting DC-SIGN, we
      have designed a new class of mannoside glycolipid conjugates. We report the
      synthesis of amphiphiles composed of a mannose head, a hydrophilic linker
      essential for solubility in aqueous media, and a lipid chain of variable length.
      These conjugates presented unusual properties based on a cooperation between the
      mannoside head and the lipid chain, which enhanced the affinity and decreased the
      need for multivalency. With an optimal lipid length, they exhibited strong
      binding affinity for DC-SIGN (K(d) in the micromolar range) as assessed by
      surface plasmon resonance. The most active molecules were branched trimannoside
      conjugates, able to inhibit the interaction of the HIV-1 envelope with DCs, and
      to drastically reduce trans-infection of HIV-1 mediated by DCs (IC(50s) in the
      low micromolar range). This new class of compounds may be of potential use for
      prevention of HIV-1 dissemination, and also of infection by other DC-SIGN-binding
      human pathogens.

PMID- 22871092
TI  - Association of HLA-DR1 with the allergic response to the major mugwort pollen
      allergen: molecular background.
AB  - BACKGROUND: Mugwort pollen allergens represent the main cause of pollinosis in
      late summer. The major allergen, Art v 1, contains only one single
      immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The
      frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and
      HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36
      also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 
      specific T cell receptors can be activated by HLA-DR4 molecules. To understand
      the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in
      HLA/peptide-binding and TCR-recognition, we investigated the molecular background
      of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4.
      RESULTS: The majority of Art v 125-36 -specific T cell lines and clones from HLA
      DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally
      processed Art v 1-peptides when presented by HLA-DR1 or HLA-DR4 expressing
      antigen presenting cells. However, at limiting peptide concentrations DR1 was
      more effective in T cell stimulation. In addition, the minimal epitope for 50% of
      Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding
      assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules
      indicated similar binding capacities and use of the same register. In silico
      simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding
      of the central part of the peptide to either molecule, but a higher flexibility
      of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1.
      CONCLUSIONS: The predominance of HLA-DR1 in the response to Art v 125-36 may be
      explained by subtle conformation changes of the peptide bound to DR1 compared to
      DR4. Computer simulation supported our experimental data by demonstrating
      differences in peptide mobility within the HLA-DR complex that may influence TCR
      binding. We suggest that the minor differences observed in vitro may be more
      relevant in the microenvironment in vivo, so that only presentation by HLA-DR1,
      but not -DR4 permits successful T cell activation.

PMID- 22871094
TI  - The changes of blood platelet activation in breast cancer patients before
      surgery, after surgery, and in various phases of the chemotherapy.
AB  - Blood platelets from patients with cancer (before or after the surgery) exhibit a
      variety of qualitative abnormalities. Different anti-cancer drugs may also induce
      the oxidative/nitrative stress in blood platelets and change their hemostatic
      properties. The aim of our study was to explain the effect of superoxide anion
      radicals ([Formula: see text]) production on hemostatic properties of blood
      platelets (activated by a strong physiological agonist - thrombin) from breast
      cancer patients before the surgery, after the surgery, and after various phases
      (I-IV) of chemotherapy (doxorubicin and cyclophosphamide). Patients were
      hospitalized in the Department of Oncological Surgery and at the Department of
      Chemotherapy, Medical University of Lodz, Poland. We measured the platelet
      aggregation as the marker of hemostatic activity of blood platelets. We observed
      an increase of [Formula: see text] in thrombin-activated blood platelets from
      patients with breast cancer (before or after the surgery and after various phases
      of the chemotherapy) compared to the healthy group. Our other experiments
      demonstrated that aggregation (induced by thrombin) of blood platelets from
      patients with breast cancer before the surgery, after the surgery, and after
      various phases of the chemotherapy differs from aggregation of platelets obtained
      from healthy volunteers. Moreover, our results showed the correlation between the
      [Formula: see text] generation and changes of platelet aggregation in breast
      cancer patients before the surgery, after the surgery, and after the chemotherapy
      (I and IV phases). Considering the data presented in this study, we suggest that
      the production of [Formula: see text] in blood platelets (activated by thrombin)
      obtained from breast cancer patients may induce the changes of platelet
      aggregation, which may contribute in thrombosis in these patients. 

PMID- 22871095
TI  - Effect of activated vitamin D on glucoparameters in HCV seropositive and
      seronegative patients on chronic hemodialysis.
AB  - INTRODUCTION: Many studies support the role of vitamin D in the pathogenesis of
      both types of diabetes. Pancreatic tissues express the vitamin D receptor (VDR)
      and vitamin D-binding protein; some allelic variations in genes involved in
      vitamin D metabolism and VDR are associated with glucose intolerance, defective
      insulin secretion, and sensitivity. Epidemiological links have been established
      between type 2 diabetes mellitus (DM) and hepatitis C virus (HCV) infection. AIM:
      To explore the possible therapeutic potential of pharmacologic doses of 1-alpha
      hydroxy vitamin D therapy in improving pancreatic beta-cell function in HCV
      seropositive hemodialysis (HD) patients. PATIENTS AND METHODS: Twenty HCV
      seropositive HD patients and 20 HCV seronegative patients as control group were
      randomly selected from HD units. 1-alpha-Hydroxy vitamin D therapy was
      administrated in the dose ranged from 0.25 to 0.5 MUg/day for 3 months. Corrected
      total serum calcium, phosphorus, intact parathyroid hormone (iPTH), 25-hydroxy
      vitamin D [25(OH) vitamin D], 1,25-dihydroxy vitamin D, and glucoparameters
      [fasting blood glucose, glycohemoglobin test (HbA1c%), homeostatic model
      assessment (HOMA)-insulin resistance, and HOMA-beta-cell function% (B%)] were
      measured under basal conditions and after 3 months of therapy. RESULTS: There was
      highly significant improvement in the concentrations of fetal bovine serum (FBS),
      serum insulin, HbA1c%, 25(OH) vitamin D, and HOMA-beta-cell function in HCV
      seropositive and HCV seronegative groups after oral 1-alphacalcidiol therapy (p <
      0.001). Positive correlation exists between the percentage increase in serum
      insulin and that in HOMA-beta-cell function versus 25(OH) vitamin D (p < 0.021
      and p < 0.027, respectively) in HCV negative group. CONCLUSION: 1-alpha-Hydroxy
      vitamin D oral therapy may improve glycemic control in HCV seropositive and HCV
      seronegative HD patients.

PMID- 22871096
TI  - Effects of psychosocial stimulation on improving home environment and child
      rearing practices: results from a community-based trial among severely
      malnourished children in Bangladesh.
AB  - BACKGROUND: Parenting programmes are effective in enhancing parenting practices
      and child development. This study evaluated the effects of a intervention with
      psychosocial stimulation (PS) on the quality of the home environment and mothers'
      child-rearing practices in a community-based trial with severely malnourished
      Bangladeshi children. METHOD: Severely underweight children (n = 507), 6-24
      months of age, were randomly assigned to five groups: PS; food supplementation
      (FS); PS + FS; clinic-control (CC); and, hospital-control (CH). PS included
      fortnightly follow-up visits for six months at community clinics where a play
      leader demonstrated play activities and gave education on child development and
      child rearing practices. FS comprised cereal-based supplements (150-300 kcal/day)
      for three months. All groups received medical care, micronutrient supplements and
      growth monitoring. Mothers were given the Home Observation for Measurement of the
      Environment (HOME) inventory and a questionnaire on parenting at baseline and
      after six months to assess the outcome. RESULTS: 322 children completed the
      study. After six months of intervention the PS + FS and PS groups benefitted in
      the total HOME score (depending on the comparison group, effect sizes varied from
      0.66 to 0.33 SD) The PS + FS and PS groups also benefitted in two HOME subscales:
      maternal involvement (effect sizes: 0.8 to 0.55 SD) and play materials, (effect
      sizes: 0.46 to 0.6 SD), and child-rearing practices scores (effect size: 1.5 to
      1.1 SD). The PS + FS group benefitted 4.0 points in total HOME score compared
      with CH, 4.8 points compared with CC and 4.5 points compared with FS (p < 0.001
      for all). The PS group benefitted 2.4 points compared with CH (p = 0.035), 3.3
      points compared with CC (p = 0.004), and 2.9 points compared with FS (p = 0.006).
      Child-rearing practice scores of the PS + FS group improved 7.7, 6.4 and 6.6
      points and the PS group improved 8.5, 7.2 and 7.4 points more than CH, CC and FS,
      respectively (p < 0.001 for all). CONCLUSIONS: Child-rearing practices of mothers
      of severely malnourished children and the quality of their home environment can
      be improved through community-based psychosocial stimulation with or without food
      supplementation. This may be of importance to promote child development.

PMID- 22871097
TI  - First case of disseminated phaeohyphomycosis in an immunocompetent individual due
      to Alternaria malorum.
AB  - A 27-year-old Iranian, previously healthy male presented with sub-cutaneous
      necrotic lesions with a localized dermatosis affecting the anterior chest, neck
      and face. These lesions consisted of singular, well-defined verrucous plaques
      which gradually developed and disseminated over time. The dermatosis was followed
      by the development of necrotic swollen lesions localized on the hard palate. The
      patient did not recall any history of trauma or puncture at any of the sites of
      infection. While histopathological examination of periodic acid-Schiff (PAS)
      stained material revealed irregular, unbranched, septate hyphae, direct
      examination (KOH 10%) of lesion samples demonstrated the presence of septate
      indistinct brownish hyphae. Alternaria malorum was isolated (CBS 126589) and its
      identity was confirmed by sequencing of the internal transcribed spacer (ITS
      rDNA). Since the palate lesion reoccurred after 10 years and the patient's
      condition did not improve with amphotericin B combination therapy, the lesion was
      surgical excised and he underwent antifungal therapy with amphotericin B and
      itraconazole. There was no dehiscence or fistula formation or any evidence of
      relapse of fungal infection during a one year follow-up and the patient was
      successfully cured. In vitro antifungal susceptibility tests revealed that the
      MIC values for those antifungals employed in this case were amphotericin B (0.125
      MUg/ml), fluconazole (32 MUg/ml), itraconazole (0.125 MUg/ml), voriconazole (1
      MUg/ml), and posaconazole (0.063 MUg/ml). The MECs for caspofungin and
      anidulafungin were 0.25 MUg/ml and 0.016 MUg/ml, respectively. However, treatment
      of A. malorum infections with the latter agents remains to be evaluated.

PMID- 22871098
TI  - Development of molecularly imprinted polymer as sustain release drug carrier for
      propranolol HCL.
AB  - Applications of molecularly imprinted polymer (MIPs), is rapidly increasing,
      especially in the drug delivery field. Molecularly imprinted polymers are the
      molecular traps, which can entrap the specific molecule and also control its
      release. Polymer complexes were prepared with and without propranolol HCl as
      templates, MAA (methacrylic acid) as monomer and EGDMA (ethyleneglycol
      dimethacrylate) as crosslinker by solvent polymerization technique. Drug release
      pattern from these polymer complexes were compared and maximum drug release in 12
      h was consider to optimize the ratio of MAA and EGDMA. Since, the maximum
      propranolol HCl release from polymer complex was low (62.15%) in optimized batch,
      inclusion complex of drug with beta-cyclodextrin were prepared for the higher
      drug release (80.32%). The selected polymer complexes were treated with methanol
      for complete removal of the drug to form MIPs. These MIPs were reloaded with the
      drug and subjected for drug release. The release patterns from reloaded MIP's
      were observed to be slightly quicker than their corresponding MIP's. 

PMID- 22871099
TI  - How to set up a low cost tele-ultrasound capable videoconferencing system with
      wide applicability.
AB  - BACKGROUND: Worldwide ultrasound equipment accessibility is at an all-time high,
      as technology improves and costs decrease. Ensuring that patients benefit from
      more accurate resuscitation and diagnoses from a user-dependent technology, such
      as ultrasound, requires accurate examination, typically entailing significant
      training. Remote tele-mentored ultrasound (RTUS) examination is, however, a
      technique pioneered in space medicine that has increased applicability on earth.
      We, thus, sought to create and demonstrate a cost-minimal approach and system
      with potentially global applicability. METHODS: The cost-minimal RTUS system was
      constructed by utilizing a standard off-the-shelf laptop computer that connected
      to the internet through an internal wireless receiver and/or was tethered through
      a smartphone. A number of portable hand-held ultrasound devices were digitally
      streamed into the laptop utilizing a video converter. Both the ultrasound video
      and the output of a head-mounted video camera were transmitted over freely
      available Voice Over Internet Protocol (VOIP) software to remote experts who
      could receive and communicate using any mobile device (computer, tablet, or
      smartphone) that could access secure VOIP transmissions from the internet.
      RESULTS: The RTUS system allowed real-time mentored tele-ultrasound to be
      conducted from a variety of settings that were inside buildings, outside on
      mountainsides, and even within aircraft in flight all unified by the simple
      capability of receiving and transmitting VOIP transmissions. . Numerous types of
      ultrasound examinations were conducted such as abdominal and thoracic
      examinations with a variety of users mentored who had previous skills ranging
      from none to expert. Internet connectivity was rarely a limiting factor, with
      competing logistical and scheduling demands of the participants predominating.
      CONCLUSIONS: RTUS examinations can educate and guide point of care clinical
      providers to enhance their use of ultrasound. The scope of the examinations
      conducted is limited only by the time available and the criticality of the
      subject being examined. As internet connectivity will only improve worldwide,
      future developments need to focus on the human factors to optimize tele
      sonographic interactions.

PMID- 22871100
TI  - Assessment of red blood cell glutathione status in insulin resistance.
AB  - The aim of this study was to assess red blood cell glutathione from insulin
      sensitive and insulin-resistant individuals before and after an oral glucose
      dose. Fifteen healthy, young (24 +/- 5 years), nonobese (23 +/- 2 kg.m-2),
      insulin-sensitive (ISI composite = 6.0 +/- 1.2) individuals and 14 healthy, young
      (22 +/- 2 years), nonobese (24 +/- 2 kg.m-2), insulin-resistant (ISI composite =
      2.7 +/- 1.1) individuals received a 75 g oral glucose dose. Blood samples were
      drawn before and for 2 h after glucose ingestion for red blood cell glutathione
      and serum glucose and insulin concentrations. Glycemia before and after glucose
      ingestion was similar between groups (p = 0.17), which suggest that
      hyperinsulinemia compensated impaired insulin sensitivity. Red blood cell total
      (p = 0.81), reduced (p = 0.79), and oxidized (p = 0.88) glutathione
      concentrations were similar between groups under fasting and postprandial
      conditions. However, in response to glucose, increases in total and reduced
      glutathione concentrations were found at the end of the 2 h assessment period in
      both groups (p < 0.05). Direct associations between postprandial glucose response
      and red blood cell total (r = 0.52; p < 0.05) and oxidized (r = 0.61; p = 0.02)
      glutathione concentrations were observed only in insulin-sensitive subjects. In
      conclusion, healthy individuals differing in their degree of insulin resistance
      showed similar red blood cell glutathione concentrations under non-glucose- and
      glucose-stimulated conditions.

PMID- 22871101
TI  - Comparison of one- and two-dimensional liquid chromatography approaches in the
      label-free quantitative analysis of Methylocella silvestris.
AB  - The proteome of the bacterium Methylocella silvestris has been characterized
      using reversed phase ultra high pressure liquid chromatography (UPLC) and two
      dimensional reversed phase (high pH)-reversed phase (low pH) UPLC prior to mass
      spectrometric analysis. Variations in protein expression levels were identified
      with the aid of label-free quantification in a study of soluble protein extracts
      from the organism grown using methane, succinate, or propane as a substrate. The
      number of first dimensional fractionation steps has been varied for 2D analyses,
      and the impact on data throughput and quality has been demonstrated. Comparisons
      have been made regarding required experimental considerations including total
      loading of biological samples required, instrument time, and resulting data file
      sizes. The data obtained have been evaluated with respect to number of protein
      identifications, confidence of assignments, sequence coverage, relative levels of
      proteins, and dynamic range. Good qualitative and quantitative agreement was
      observed between the different approaches, and the potential benefits and
      limitations of the reversed phase-reversed phase UPLC technique in label-free
      analysis are discussed. A preliminary screen of the protein regulation data has
      also been performed, providing evidence for a possible propane assimilation
      route.

PMID- 22871102
TI  - Hydrodefluorination and hydrogenation of fluorobenzene under mild aqueous
      conditions.
AB  - Fluorinated organic compounds are increasingly used in many applications, and
      their release to the environment is expected. It is therefore important to find
      suitable methods for degradation of fluorinated compounds under environmentally
      relevant conditions. In this study, a simple heterogeneous rhodium-based
      catalytic system (Rh/Al(2)O(3) and H(2)) for hydrodefluorination and
      hydrogenation of fluorobenzene under mild aqueous conditions (1 atm of H(2),
      ambient temperature) was developed and the underlying reaction mechanism was
      investigated. Fluorobenzene degraded rapidly (t(1/2) ~ 0.2 h) to form cyclohexane
      and fluoride (F(-)) as the stable end products, with benzene and cyclohexene
      observed as intermediates. Cyclohexadiene intermediates were not observed but
      were expected to form during the hydrogenation of benzene. Three postulated but
      unobserved fluorinated intermediates were subjected to the catalytic reaction
      conditions, and it was concluded that they most likely do not form during the
      fluorobenzene degradation reaction. Isotope labeling experiments showed that the
      unsaturated intermediates undergo rapid and reversible
      hydrogenation/dehydrogenation under the reaction conditions and also that fully
      saturated compounds are unreactive in the catalytic system. Both molecular
      hydrogen and water were sources of hydrogen in the final cyclohexane product.
      Kinetic fitting indicated that sorption/desorption of fluorobenzene onto the
      catalyst surface plays an important role in the mechanism.

PMID- 22871103
TI  - Prevalence and under-detection of gambiense human African trypanosomiasis during
      mass screening sessions in Uganda and Sudan.
AB  - BACKGROUND: Active case detection through mass community screening is a major
      control strategy against human African trypanosomiasis (HAT, sleeping sickness)
      caused by T. brucei gambiense. However, its impact can be limited by incomplete
      attendance at screening sessions (screening coverage) and diagnostic inaccuracy.
      METHODS: We developed a model-based approach to estimate the true prevalence and
      the fraction of cases detected during mass screening, based on observed
      prevalence, and adjusting for incomplete screening coverage and inaccuracy of
      diagnostic algorithms for screening, confirmation and HAT stage classification.
      We applied the model to data from three Medecins Sans Frontieres projects in
      Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri). RESULTS: We analysed 604
      screening sessions, targeting about 710,000 people. Cases were about twice as
      likely to attend screening as non-cases, with no apparent difference by stage.
      Past incidence, population size and repeat screening rounds were strongly
      associated with observed prevalence. The estimated true prevalence was 0.46% to
      0.90% in Kiri depending on the analysis approach, compared to an observed
      prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to
      0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2
      cases was around two-three times higher than that observed, due to stage
      misclassification. The estimated detected fraction was between 42.2% and 84.0% in
      Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe. CONCLUSIONS:
      In these well-resourced projects, a moderate to high fraction of cases appeared
      to be detected through mass screening. True prevalence differed little from
      observed prevalence for monitoring purposes. We discuss some limitations to our
      model that illustrate several difficulties of estimating the unseen burden of
      neglected tropical diseases.

PMID- 22871104
TI  - Effects of sildenafil and/or muscle derived stem cells on myocardial infarction.
AB  - BACKGROUND: Previous studies have shown that long-term oral daily PDE 5
      inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction
      in tissues of various rat organs and that implantation of skeletal muscle-derived
      stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in
      combination were found to be more effective in non-MI cardiac repair than each
      treatment separately. We have now investigated whether sildenafil at lower doses
      and MDSC, alone or in combination are effective to attenuate LV remodeling after
      MI in rats. METHODS: MI was induced in rats by ligature of the left anterior
      descending coronary artery. Treatment groups were: "Series A": 1) untreated; 2)
      oral sildenafil 3 mg/kg/day from day 1; and "Series B": intracardiac injection at
      day 7 of: 3) saline; 4) rat MDSC (106 cells); 5) as #4, with sildenafil as in #2.
      Before surgery, and at 1 and 4 weeks, the left ventricle ejection fraction (LVEF)
      was measured. LV sections were stained for collagen, myofibroblasts, apoptosis,
      cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots
      estimated angiogenesis and myofibroblast accumulation, as well as potential
      sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9
      in serum. RESULTS: As compared to untreated MI rats, sildenafil improved LVEF,
      reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac
      troponin T. MDSC replicated most of these effects and stimulated cardiac
      angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and
      endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated
      PDE 5. CONCLUSIONS: Long-term oral sildenafil, or MDSC given separately, reduce
      the MI fibrotic scar and improve left ventricular function in this rat model. The
      failure of the treatment combination may be due to inducing overexpression of
      PDE5.

PMID- 22871105
TI  - Saliva and plasma TIMP-1 in patients with colorectal cancer: a prospective study.
AB  - BACKGROUND AND AIMS: A prospective cross-sectional study was designed to test if
      total levels of TIMP-1 in saliva and plasma correlated with the diagnosis of
      colorectal cancer (CRC) in a population with symptoms consistent with this
      disease. MATERIALS AND METHODS: Stimulated whole saliva and blood samples were
      collected from 161 individuals referred to colonoscopy with symptoms associated
      with CRC. The results of the examination, as well as previous and/or current
      other diseases were recorded. In a blinded study, the authors used an in-house
      TIMP-1 ELISA previously validated for use in saliva and plasma to determine total
      levels of TIMP-1. RESULTS: Fifty-six of the patients (35%) were diagnosed with
      CRC. Plasma TIMP-1 levels were significantly elevated in CRC patients compared
      with patients with other, non-malignant diseases and individuals without disease.
      Significant differences in saliva TIMP-1 levels between CRC patients and
      individuals without CRC could not be demonstrated. In addition, no correlation
      was found between levels of TIMP-1 in plasma and saliva. CONCLUSION: Total levels
      of TIMP-1 in saliva do not reflect the presence of CRC, and TIMP-1 saliva
      measurements thus cannot substitute plasma TIMP-1 measurements in detection of
      CRC.

PMID- 22871106
TI  - One-step synthesis of cellulose from cellobiose via protic acid-assisted
      enzymatic dehydration in aprotic organic media.
AB  - Direct and efficient enzymatic synthesis of long-chain cellulose from cellobiose
      in its original form was successfully achieved via the combination of a
      surfactant-enveloped enzyme (SEE) and a protic acid in an aprotic organic
      solvent, lithium chloride/N,N-dimethylacetamide system. The SEE biocatalyst was
      prepared by protecting the surface of cellulase with the nonionic surfactant
      dioleyl-N-D-glucona-L-glutamate for keeping its enzymatic activity in nonaqueous
      media. Fourier transform infrared and nuclear magnetic resonance analyses
      elucidated the successful synthesis of cellulose, beta-1,4-linked D-glucopyranose
      polymer, through the reverse hydrolysis of cellobiose. By using protic acid
      cocatalysts, a degree of polymerization of as-synthesized cellulose reached more
      than 120, in a ca. 26% conversion, which was 5 times higher than that obtained in
      an acid-free SEE system. A novel-concept biocatalysis, i.e., a protic acid
      assisted SEE-mediated reaction, enables a facile, one-step chain elongation of
      carbohydrates without any activation via multistep organic chemistry, and can
      provide potential applications in the functional design of glycomaterials.

PMID- 22871107
TI  - Psychosocial group intervention to enhance self-management skills of people with
      dementia and their caregivers: study protocol for a randomized controlled trial.
AB  - BACKGROUND: After diagnosis of a dementing illness, patients and their spouses
      have many concerns related to the disease and their future. This often leads to
      poor psychological well-being and reduced health-related quality of life (HRQoL)
      of the family. Support for self-management skills has been proven to be an
      effective method to improve prognosis of asthma, heart failure and
      osteoarthritis. However, self-management interventions have not been studied in
      dementia. Therefore, our aim was to examine, in an objective-oriented group
      intervention, the efficacy of self-management support program (SMP) on the HRQoL
      of dementia patients and their spousal caregivers as well as on the sense of
      competence and psychological well-being of caregivers. METHODS: During the years
      2011 to 12, 160 dementia patients and their spouses will be recruited from memory
      clinics and randomized into two arms: 80 patients for group-based SMP sessions
      including topics selected by the participants, 80 patients will serve as controls
      in usual community care. Sessions may include topics on dementia, community
      services, active lifestyle and prevention for cognitive decline, spousal
      relationship, future planning and emotional well-being. The patients and spouses
      will have their separate group sessions (ten participants per group) once a week
      for eight weeks. Main outcome measures will be patients' HRQoL (15D) and spousal
      caregivers' HRQoL (RAND-36), and sense of competence (SCQ). Secondary measures
      will be caregivers' psychological well-being (GHQ-12) and coping resources,
      patients' depression, cognition and signs of frailty. Data concerning admissions
      to institutional care and the use and costs of health and social services will be
      collected during a two-year follow-up. DISCUSSION: This is a 'proof-of-concept'
      study to explore the efficacy of group support for self-management skills among
      dementia families. It will also provide data on cost-effectiveness of the
      intervention. TRIAL REGISTRATION: ACTRN12611001173987.

PMID- 22871108
TI  - Granulomatous interstitial nephritis in a patient with Crohn's disease.
AB  - A case of granulomatous interstitial nephritis (GIN) associated with Crohn's
      disease (CD) was reported. GIN is a rare pathological finding in renal biopsy
      specimens. In a patient affected by CD, granulomas may be found in various
      tissues and organs such as lymph nodes, mesentery, liver, and lungs and
      occasionally in bones, joints, and skeletal muscle. Few cases of granuloma have
      been reported in the kidney, and it is not always possible to relate the presence
      of granuloma to CD, to other interstitial granulomatosis diseases, or to a drug
      induced reaction. The issue has a remarkable clinical effect; indeed, the answer
      requires a completely different therapeutic approach. The diagnosis analysis on
      the basis of clinical-pathological evidences and on reports from literature is
      discussed.

PMID- 22871109
TI  - Ultrasound-guided oblique approach for peripheral venous access in a phantom
      model.
AB  - BACKGROUND: Ultrasound (US) vascular guidance is traditionally performed in
      transverse (T) and longitudinal (L) axes, each with drawbacks. We hypothesized
      that the introduction of a novel oblique (O) approach would improve the success
      of US-guided peripheral venous access. We examined emergency physician (EP)
      performance using the O approach in a gel US phantom. METHODS: In a prospective,
      case control study, EPs were enrolled from four levels of physician experience
      including postgraduate years one to three (PGY1, PGY2, PGY3) and attending
      physicians. After a brief training session, each participant attempted vessel
      aspiration using a linear probe in T, L, and O axes on a gel US phantom. Time to
      aspiration and number of attempts to aspiration were recorded. The approach order
      was randomized, and descriptive statistics were used. RESULTS: Twenty-four
      physicians participated. The first-attempt success rate was lower for O, 45.83%,
      versus 70.83% for T (p = 0.03) and 83.33% for L (p = 0.01). The average time to
      aspiration was 12.5 s (O) compared with 9.47 s (T) and 9.74 s (L), respectively.
      There were no significant differences between all four groups in regard to total
      amount of time and number of aspiration attempts; however, a trend appeared
      revealing that PGY3 and attending physicians tended to aspirate in less time and
      by fewer attempts in all three orientations when compared with the PGY2 and PGY1
      physicians. CONCLUSION: In this pilot study, US-guided simulated peripheral
      venous access using a phantom gel model in a mixed user group showed that the
      novel oblique approach was not initially more successful versus T and L
      techniques.

PMID- 22871110
TI  - Immune responses in dogs with cutaneous adverse food reactions.
AB  - Adverse food reactions (AFR) in dogs are reactions due to apparently harmless
      food antigens, with an unknown aetiology, i.e. immunopathogenesis. Despite the
      entry of food allergens via the intestinal tract, in the majority of dogs with
      AFR, clinical symptoms are only associated with the skin (CAFR). In the present
      review, factors are presented of relevance in triggering the differentiation of
      naive T cells into effector T cell types and the role of these T cell types in
      allergy. More specifically, the allergic immune responses in intestine and skin
      are discussed in this article as well as the potential pathways, e.g. homing of
      antigen presenting cells or allergen-induced T cells to the skin, of induction of
      cutaneous symptoms.

PMID- 22871111
TI  - The specificity and organisation of autobiographical memories.
AB  - Previous research suggests that autobiographical memories are over-general and
      are organised according to life periods. One experiment assessed the specificity
      and organisation of autobiographical memory by manipulating two variables. The
      retrieval cues were either a set of three words (a theme, a time period, and an
      emotional valence) or a short narrative that included a specific theme, time
      period, and emotional valence. The instructions either encouraged the
      participants to respond as though they were conversing with a friend (social
      instructions) or did not specify a target audience (standard instructions).
      Narrative cues and standard instructions elicited more specific responses than
      word cues and social instructions, respectively. Whereas word cues elicited
      memories that were most likely to match the cues in terms of time period,
      narrative cues elicited memories that were most likely to match the cues in terms
      of theme. These data suggest that previous research underestimated the
      specificity of the autobiographical knowledge base and overestimated the
      importance of temporally defined life periods for organising autobiographical
      memory. Previous conclusions regarding the specificity and organisation of
      autobiographical memory may reflect the structure of autobiographical narratives
      and the methodologies used to collect such narratives rather than the content of
      autobiographical memory itself.

PMID- 22871112
TI  - PKMiner: a database for exploring type II polyketide synthases.
AB  - BACKGROUND: Bacterial aromatic polyketides are a pharmacologically important
      group of natural products synthesized by type II polyketide synthases (type II
      PKSs) in actinobacteria. Isolation of novel aromatic polyketides from microbial
      sources is currently impeded because of the lack of knowledge about prolific taxa
      for polyketide synthesis and the difficulties in finding and optimizing target
      microorganisms. Comprehensive analysis of type II PKSs and the prediction of
      possible polyketide chemotypes in various actinobacterial genomes will thus
      enable the discovery or synthesis of novel polyketides in the most plausible
      microorganisms. DESCRIPTION: We performed a comprehensive computational analysis
      of type II PKSs and their gene clusters in actinobacterial genomes. By
      identifying type II PKS subclasses from the sequence analysis of 280 known type
      II PKSs, we developed highly accurate domain classifiers for these subclasses and
      derived prediction rules for aromatic polyketide chemotypes generated by
      different combinations of type II PKS domains. Using 319 available
      actinobacterial genomes, we predicted 231 type II PKSs from 40 PKS gene clusters
      in 25 actinobacterial genomes, and polyketide chemotypes corresponding to 22
      novel PKS gene clusters in 16 genomes. These results showed that the
      microorganisms capable of producing aromatic polyketides are specifically
      distributed within a certain suborder of Actinomycetales such as
      Catenulisporineae, Frankineae, Micrococcineae, Micromonosporineae,
      Pseudonocardineae, Streptomycineae, and Streptosporangineae. CONCLUSIONS: We
      could identify the novel candidates of type II PKS gene clusters and their
      polyketide chemotypes in actinobacterial genomes by comprehensive analysis of
      type II PKSs and prediction of aromatic polyketides. The genome analysis results
      indicated that the specific suborders in actinomycetes could be used as prolific
      taxa for polyketide synthesis. The chemotype-prediction rules with the suggested
      type II PKS modules derived using this resource can be used further for microbial
      engineering to produce various aromatic polyketides. All these resources,
      together with the results of the analysis, are organized into an easy-to-use
      database PKMiner, which is accessible at the following URL:
      http://pks.kaist.ac.kr/pkminer. We believe that this web-based tool would be
      useful for research in the discovery of novel bacterial aromatic polyketides.

PMID- 22871114
TI  - Making room for breastfeeding on the worldwide agenda.

PMID- 22871113
TI  - Synaptic protein ubiquitination in rat brain revealed by antibody-based
      ubiquitome analysis.
AB  - Protein ubiquitination is an essential post-translational modification regulating
      neurodevelopment, synaptic plasticity, learning, and memory, and its
      dysregulation contributes to the pathogenesis of neurological diseases. Here we
      report a systematic analysis of ubiquitinated proteome (ubiquitome) in rat brain
      using a newly developed monoclonal antibody that recognizes the diglycine tag on
      lysine residues in trypsinized peptides (K-GG peptides). Initial antibody
      specificity analysis showed that the antibody can distinguish K-GG peptides from
      linear GG peptides or pseudo K-GG peptides derived from iodoacetamide. To
      evaluate the false discovery rate of K-GG peptide matches during database search,
      we introduced a null experiment using bacterial lysate that contains no such
      peptides. The brain ubiquitome was then analyzed by this antibody enrichment with
      or without strong cation exchange (SCX) prefractionation. During SCX
      chromatography, although the vast majority of K-GG peptides were detected in the
      fractions containing at least three positive charged peptides, specific K-GG
      peptides with two positive charges (e.g., protein N-terminal acetylated and C
      terminal non-K/R peptides) were also identified in early fractions. The
      reliability of C-terminal K-GG peptides was also extensively investigated.
      Finally, we collected a data set of 1786 K-GG sites on 2064 peptides in 921
      proteins and estimated their abundance by spectral counting. The study reveals a
      wide range of ubiquitination events on key components in presynaptic region
      (e.g., Bassoon, NSF, SNAP25, synapsin, synaptotagmin, and syntaxin) and
      postsynaptic density (e.g., PSD-95, GKAP, CaMKII, as well as receptors for NMDA,
      AMPA, GABA, serotonin, and acetylcholine). We also determined ubiquitination
      sites on amyloid precursor protein and alpha synuclein that are thought to be
      causative agents in Alzhermer's and Parkinson's disorders, respectively. As K-GG
      peptides can also be produced from Nedd8 or ISG15 modified proteins, we
      quantified these proteins in the brain and found that their levels are less than
      2% of ubiquitin. Together, this study demonstrates that a large number of
      neuronal proteins are modified by ubiquitination and provides a feasible method
      for profiling the ubiquitome in the brain.

PMID- 22871115
TI  - Gold nanoparticle films as sensitive and reusable elemental mercury sensors.
AB  - We demonstrate the utility of gold nanoparticles (AuNPs) as the basis of a stand
      alone, inexpensive, and sensitive mercury monitor. Gold nanoparticles absorb
      visible light due to localized surface plasmon resonance (LSPR), and the
      absorbance changes when mercury combines with the gold nanoparticles. The
      sensitivity of the peak absorbance is proportional to the surface-area-to-volume
      ratio. We chose 5 nm spheres because they have the largest surface-area-to-volume
      ratio while still having a peak absorption in the visible range. The adsorption
      of 15 atoms of Hg causes a 1 nm shift in the LSPR wavelength of these particles.
      Assembled into a film using the Langmuir-Blodgett method, the AuNP LSPR can be
      tracked with a simple UV-vis spectrometer. The rate of shift in the peak
      absorbance is linear with mercury concentrations from 1 to 825 MUg(Hg)/m(air)(3).
      Increasing the flow velocity (and mass transfer rate) increases the peak shift
      rate making this system a viable method for direct ambient mercury vapor
      measurements. Regeneration of the sensing films, done by heating to 160  degrees
      C, allows for repeatable measurements on the same film.

PMID- 22871119
TI  - Application of mathematical modeling for the development and optimization
      formulation with bioactive copper complex.
AB  - New formulation for treatment a copper deficiency in human organism was developed
      and optimized by application of mathematical modeling. This formulation contained
      copper (II) complex with polysaccharide pullulan, as active substance. The binder
      concentration [polyvinyl pyrrolidone (PVP %)], the disintegrant concentration
      (corn starch %) and the resistance to crushing (hardness) were taken as
      independent variables. In vitro measured drug release characteristics of the
      tablets at pH 1.20 and 7.56 were studied as response variables. Initially, the
      created full factorial 2(3) model showed that the resistance to crushing has the
      most significant effect on copper (II) complex release from the formulation.
      Optimal tablet formulation F2, with lower Hardness (50 N), lower Starch (20.0%)
      and higher PVP (2.7%) concentrations, is selected using the partial least squares
      (PLS) regression modeling. The selected formulation F2 has expressed the best
      drug release profile at both pH (98.66% pH = 1.20; 93.35% pH = 7.56), and the
      lowest variation of tablets weight. The presented theoretical approach and
      created PLS model can be readily applied in future copper complexes studies and
      formulation design.

PMID- 22871120
TI  - A robust dual reporter system to visualize and quantify gene expression mediated
      by transcription activator-like effectors.
AB  - BACKGROUND: Transcription activator-like effectors (TALEs) are a class of
      naturally occurring transcription effectors that recognize specific DNA sequences
      and modulate gene expression. The modularity of TALEs DNA binding domain enables
      sequence-specific perturbation and offers broad applications in genetic and
      epigenetic studies. Although the efficient construction of TALEs has been
      established, robust functional tools to assess their functions remain lacking.
      RESULTS: We established a dual reporter system that was specifically designed for
      real-time monitoring and quantifying gene expression mediated by TALEs. We
      validated both sensitivity and specificity of this dual-reporter system in
      mammalian cells, and demonstrated that this dual reporter system is robust and
      potentially amenable to high throughput (HTP) applications. CONCLUSION: We have
      designed, constructed and validated a novel dual reporter system for assessing
      TALE mediated gene regulations. This system offers a robust and easy-to- use tool
      for real-time monitoring and quantifying gene expression in mammalian cells.

PMID- 22871121
TI  - Efficacy of a combination of 10% imidacloprid and 1% moxidectin against Caparinia
      tripilis in African pygmy hedgehog (Atelerix albiventris).
AB  - BACKGROUND: The efficacy and safety of a combination formulation of 10%
      imidacloprid + 1.0% moxidectin spot-on (Advocate(r) for Cats, Bayer Animal Health
      GmbH, Leverkusen, Germany) was tested in 40 African pygmy hedgehogs (Atelerix
      albiventris) naturally infested with Caparinia tripilis. METHODS: The optimal
      dosage level of the combination for hedgehogs was determined by assigning 20
      hedgehogs into three treatment groups (0.1, 0.4 and 1.6 ml/Kg b.w.), and one
      untreated control group of 5 hedgehogs each. Twenty naturally infested hedgehogs
      were then randomly assigned to either treatment or control group with 10 animals
      each, and the number of live mites was counted from 13 body regions on day 0, 3,
      9, 16, and 30 after single treatment at the dosage level of 0.1 ml/Kg. RESULTS:
      Before the chemotherapy, the highest density of mite was observed in external ear
      canals followed by the dorsal and the lowest in the ventral regions of the body
      surface. The dosage level of 0.1 ml/Kg, which corresponded to the recommended
      dosage level for cats, containing 10 mg imidacloprid and 1 mg moxidectin was also
      the optimal dosage level for hedgehogs. No hedgehogs in the treatment group
      showed live mites from day 3 post treatment. Side effects such as ataxia,
      depression, nausea, and weight fluctuation were not observed during the whole
      period of study. CONCLUSIONS: This report suggests that a combination formulation
      of 0.1 ml/Kg of 10% imidacloprid + 1% moxidectin spot-on for cats is also useful
      for the control of Caparinia tripilis infestation in hedgehogs.

PMID- 22871122
TI  - Investigating the effect of black tea consumption during pregnancy on the
      oxidant/antioxidant status of breastmilk.
AB  - OBJECTIVE: Black tea is associated with antioxidant properties. The objective of
      this study was to investigate the effect of the amount of black tea consumption
      during pregnancy on the oxidant/antioxidant status of breastmilk. SUBJECTS AND
      METHODS: Breastmilk was obtained from 30 mothers and analyzed for lipid
      peroxidation based on levels of malondialdehyde (MDA) and of reduced glutathione
      (GSH). In a survey completed by all participants, daily black tea consumption
      during the pregnancy was reported. RESULTS: No correlation was found between the
      amount of black tea consumed and levels of MDA (p=0.401) and/or GSH (p=0.473).
      The results of this study indicate that consumption of varying amounts of black
      tea does not affect the oxidant/antioxidant status of breastmilk. CONCLUSIONS:
      The insensitivity of breastmilk to antioxidant contributions by black tea
      reflects the capacity of breastmilk to be resistant to the myriad of factors that
      otherwise affect a pregnant woman.

PMID- 22871123
TI  - Assessing the levels of food shortage using the traffic light metaphor by
      analyzing the gathering and consumption of wild food plants, crop parts and crop
      residues in Konso, Ethiopia.
AB  - BACKGROUND: Humanitarian relief agencies use scales to assess levels of critical
      food shortage to efficiently target and allocate food to the neediest. These
      scales are often labor-intensive. A lesser used approach is assessing gathering
      and consumption of wild food plants. This gathering per se is not a reliable
      signal of emerging food stress. However, the gathering and consumption of some
      specific plant species could be considered markers of food shortage, as it
      indicates that people are compelled to eat very poor or even health-threatening
      food. METHODS: We used the traffic light metaphor to indicate normal (green),
      alarmingly low (amber) and fully depleted (red) food supplies and identified
      these conditions for Konso (Ethiopia) on the basis of wild food plants (WFPs),
      crop parts (crop parts not used for human consumption under normal conditions;
      CPs) and crop residues (CRs) being gathered and consumed. Plant specimens were
      collected for expert identification and deposition in the National Herbarium. Two
      hundred twenty individual households free-listed WFPs, CPs, and CRs gathered and
      consumed during times of food stress. Through focus group discussions, the
      species list from the free-listing that was further enriched through key
      informants interviews and own field observations was categorized into species
      used for green, amber and red conditions. RESULTS: The study identified 113 WFPs
      (120 products/food items) whose gathering and consumption reflect the three
      traffic light metaphors: red, amber and green. We identified 25 food items for
      the red, 30 food items for the amber and 65 food items for the green metaphor. We
      also obtained reliable information on 21 different products/food items (from 17
      crops) normally not consumed as food, reflecting the red or amber metaphor and 10
      crop residues (from various crops), plus one recycled stuff which are used as
      emergency foods in the study area clearly indicating the severity of food stress
      (red metaphor) households are dealing with. Our traffic light metaphor proved
      useful to identify and closely monitor the types of WFPs, CPs, and CRs collected
      and consumed and their time of collection by subsistence households in rural
      settings. Examples of plant material only consumed under severe food stress
      included WFPs with health-threatening features like Dobera glabra (Forssk.) Juss.
      ex Poir. and inkutayata, parts of 17 crops with 21 food items conventionally not
      used as food (for example, maize tassels, husks, empty pods), ten crop residues
      (for example bran from various crops) and one recycled food item (tata).
      CONCLUSIONS: We have complemented the conventional seasonal food security
      assessment tool used by humanitarian partners by providing an easy, cheap tool to
      scale food stress encountered by subsistence farmers. In cognizance of
      environmental, socio-cultural differences in Ethiopia and other parts of the
      globe, we recommend analogous studies in other parts of Ethiopia and elsewhere in
      the world where recurrent food stress also occurs and where communities
      intensively use WFPs, CPs, and CRs to cope with food stress.

PMID- 22871124
TI  - Metal-free DNA linearized nuclease based on PASP-polyamine conjugates.
AB  - Genome manipulation controlled by small metal complexes has attracted extensive
      interest because of their potential application in the fields of molecular
      biotechnology and drug development. However, their medicinal application is still
      limited due to the distinct toxicity of the free radicals generated by partial
      metal complexes based on oxidative cleaving processes. Thus, it is still a
      challenge for us to use metal free agent to cleave DNA. In this work, we showed
      that a family of polyamine-grafted PASP (poly(aspartic acid)) conjugates is able
      to rapidly induce DNA cleavage in the absence of metal ions, and obtain a high
      yield linearization product via a hydrolytic path. From the results of detailed
      control experiments, it was revealed that the formation of polyamine
      cation/phosphate anion pair and free ungrafted nucleophilic groups would be the
      key factors to improve DNA linearization. Constructing polyamine conjugates based
      on short peptide such as polyamine-grafted PASP, as achieved here, could provide
      an attractive strategy for developing mild and efficient artificial nucleases as
      well as researching catalytic mechanisms on DNA chemistry.

PMID- 22871125
TI  - Automatic online spike sorting with singular value decomposition and fuzzy C-mean
      clustering.
AB  - BACKGROUND: Understanding how neurons contribute to perception, motor functions
      and cognition requires the reliable detection of spiking activity of individual
      neurons during a number of different experimental conditions. An important
      problem in computational neuroscience is thus to develop algorithms to
      automatically detect and sort the spiking activity of individual neurons from
      extracellular recordings. While many algorithms for spike sorting exist, the
      problem of accurate and fast online sorting still remains a challenging issue.
      RESULTS: Here we present a novel software tool, called FSPS (Fuzzy SPike
      Sorting), which is designed to optimize: (i) fast and accurate detection, (ii)
      offline sorting and (iii) online classification of neuronal spikes with very
      limited or null human intervention. The method is based on a combination of
      Singular Value Decomposition for fast and highly accurate pre-processing of spike
      shapes, unsupervised Fuzzy C-mean, high-resolution alignment of extracted spike
      waveforms, optimal selection of the number of features to retain, automatic
      identification the number of clusters, and quantitative quality assessment of
      resulting clusters independent on their size. After being trained on a short
      testing data stream, the method can reliably perform supervised online
      classification and monitoring of single neuron activity. The generalized
      procedure has been implemented in our FSPS spike sorting software (available free
      for non-commercial academic applications at the address:
      http://www.spikesorting.com) using LabVIEW (National Instruments, USA). We
      evaluated the performance of our algorithm both on benchmark simulated datasets
      with different levels of background noise and on real extracellular recordings
      from premotor cortex of Macaque monkeys. The results of these tests showed an
      excellent accuracy in discriminating low-amplitude and overlapping spikes under
      strong background noise. The performance of our method is competitive with
      respect to other robust spike sorting algorithms. CONCLUSIONS: This new software
      provides neuroscience laboratories with a new tool for fast and robust online
      classification of single neuron activity. This feature could become crucial in
      situations when online spike detection from multiple electrodes is paramount,
      such as in human clinical recordings or in brain-computer interfaces.

PMID- 22871126
TI  - Biexciton quantum yield heterogeneities in single CdSe (CdS) core (shell)
      nanocrystals and its correlation to exciton blinking.
AB  - We explore biexciton (BX) nonradiative recombination processes in single
      semiconductor nanocrystals (NCs) using confocal fluorescence microscopy and
      second-order photon intensity correlation. More specifically, we measure the
      photoluminescence blinking and BX quantum yields (QYs) and study the correlation
      between these two measurements for single core (shell) CdSe (CdS) nanocrystals
      (NCs). We find that NCs with a high "on" time fraction are significantly more
      likely to have a high BX QY than NCs with a low "on" fraction, even though the BX
      QYs of NCs with a high "on" fraction vary dramatically. The BX QYs of single NCs
      are also weakly dependent upon excitation wavelength. The weak correlation
      between exciton "on" fractions and BX QYs suggests that multiple recombination
      processes are involved in the BX recombination. To explain our results, we
      propose a model that combines both trapping and an Auger mechanism for BX
      recombination.

PMID- 22871127
TI  - Biotinylated polyacrylamide-based metal-chelating polymers and their influence on
      antigen recognition following conjugation to a trastuzumab Fab fragment.
AB  - We report the synthesis and characterization of metal-chelating polymers (MCPs)
      with a terminal biotin and a polyacrylamide backbone harboring multiple
      diethylenetriaminepentaacetic acid (DTPA) chelating sites. These polymers are
      conjugated to a streptavidin (SAv)-modified Fab fragment of trastuzumab (tmFab)
      and subsequently complexed with (111)In through DTPA. Trastuzumab has specific
      targeting ability toward human epidermal growth factor receptor-2 (HER2), which
      is overexpressed on some types of breast cancer cells and ovarian cancer cells.
      (111)In can generate Auger electrons which cause lethal DNA double strand breaks.
      The radioimmunoconjugates (RICs) were designed to target HER2 overexpressing
      cancer cells and carry multiple copies of (111)In to these cells. The mole
      maximum specific activities of these polymers were investigated by loading the
      polymers with (111)In at an increasing (111)In to polymer ratio. The polymers
      show 55-fold to 138-fold higher maximum specific activity than DTPA modified
      tmFab-SAv. Moreover, the HER2 immunoreactivities of these RICs were evaluated by
      measuring their specific binding ability toward HER2 overexpressing SKOV-3
      ovarian cancer cells. The results demonstrate that although in the presence of
      polymer there is increased nonspecific binding, HER2 targeting ability was
      retained, ensuring the radionuclide delivery ability of these RICs.

PMID- 22871128
TI  - Dietary sodium citrate supplementation enhances rehydration and recovery from
      rapid body mass loss in trained wrestlers.
AB  - This study assessed the effects of dietary sodium citrate supplementation during
      a 16 h recovery from 5% rapid body mass loss (RBML) on physiological functions,
      affective state, and performance in trained wrestlers. Sixteen wrestlers
      performed an upper body intermittent sprint performance (UBISP) test under three
      conditions: before RBML, after RBML, and after a 16 h recovery from RBML. During
      recovery, the subjects ate a prescribed diet supplemented with sodium citrate
      (600 mg.kg(-1); CIT group, N = 8) or placebo (PLC group, N = 8) and drank water
      ad libitum. RBML reduced (p < 0.05) UBISP mean power and increased urine specific
      gravity (USG). Reduction in mean power was associated with changes in plasma
      volume (PV) (r = 0.649, p = 0.006) and USG (r = -0.553, p = 0.026). During the 16
      h recovery, increases in body mass (BM) and PV were greater (p < 0.05) in the CIT
      group than in the PLC group. BM gain was associated with water retention in the
      CIT group (r = 0.899, p = 0.002) but not in the PLC group (r = 0.335, p = 0.417).
      Blood pH, HCO(3)(-) concentration, and base excess increased (p < 0.05) only in
      the CIT group. Changes in UBISP, general negative affect, and general positive
      affect did not differ in the two groups. In conclusion, ingestion of sodium
      citrate increases blood buffering capacity and PV and stimulates BM regain during
      a 16 h recovery from RBML in trained wrestlers. However, sodium citrate does not
      improve UBISP nor does it have an impact on the affective state.

PMID- 22871129
TI  - Factors affecting the occurrence and transport of atmospheric organochlorines in
      the China Sea and the northern Indian and South East Atlantic Oceans.
AB  - Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are
      reported in 97 air samples collected on board the RV Polarstern in November 2007
      from the equator to Cape Town, South Africa and the MV Oceanic II (The Scholar
      Ship) in January-March 2008 from Shanghai, China to Cape Verde in the Central
      Atlantic Ocean. The atmospheric concentrations were higher close to the coast and
      lower in remote regions of the Indian and South Atlantic Ocean. Groups of samples
      were selected in the South China Sea, Indian Ocean and South Atlantic Ocean where
      the relative wind direction matched the trajectory of the ship, thus all the
      samples had the same input of sources upwind. In these three regions the
      concentrations of OCPs and PCBs declined during atmospheric transport following
      first order kinetics. These sets of measurements provided estimates of field
      derived residence times (FDRTs) for individual compounds. These values were
      compared with predicted atmospheric residence times (PARTs) computed using a
      model of long-range atmospheric transport potential of POPs. The FDRTs are 5-10
      times longer for the more volatile PCB congeners and TC, CC, p,p'-DDT and p,p'
      DDE than the respective PARTs, while they are similar to PARTs for the less
      volatile compounds. Possible causes of discrepancies between PARTs and FDRTs are
      discussed, and revolatilization from the ocean surface seems to be the main cause
      for the higher values of FDRTs of the more volatile compounds in comparison with
      the respective PARTs.

PMID- 22871130
TI  - The sonographic digital portfolio: a longitudinal ultrasound image tracking
      program.
AB  - BACKGROUND: Ultrasonography (US) at the medical student level is developing. As
      clinical skills and simulation centers expand, US equipment miniaturizes, and
      more students are exposed to ultrasound; a digital portfolio comprised of US
      images and videos may be useful in demonstrating experience and possibly
      competency. METHODS: Medical students participated in US curricula consisting of
      didactics and hands-on training. From 1 July 2006 to 30 June 2008, student images
      and videos were saved. Total images and videos were evaluated and catalogued.
      RESULTS: A total of 10,074 images and 1,227 videos were saved during the 2-year
      period. For the academic year 2006 to 2007, 159 medical students obtained 3,641
      of the images (84.9%) and 270 of the videos (86.0%). First year students obtained
      778 images and 20 videos; second year students, 1,174 images and 64 videos; third
      year students, 211 images and 20 videos; and fourth year students, 1,478 images
      and 166 videos.For the academic year 2007 to 2008, 222 medical students obtained
      4,340 images (75%) and 619 videos (67.8%). First year students obtained 624
      images and 109 videos; second year students, 555 images and 81 videos; third year
      students, 132 images and 14 videos; and fourth year students, 3,029 images and
      415 videos. CONCLUSIONS: The ultrasound digital portfolio allows medical students
      to collate and document their ultrasound experience. Currently, there is no
      requirement for ultrasound training, documentation of competency, or minimum
      numbers of US exams for medical education. The ultrasound digital portfolio may
      be a useful tool in documenting ultrasound proficiency.

PMID- 22871131
TI  - Hepatitis B virus encoded X protein suppresses apoptosis by inhibition of the
      caspase-independent pathway.
AB  - Hepatitis B virus (HBV) encoded X protein (HBx) has been implicated in apoptotic
      and related pathogenic events during hepatocellular carcinoma. However, the
      underlying molecular mechanism through which HBx acts is largely unclear. We used
      tandem affinity purification under mild conditions to gain insight into the HBx
      interactome in HBV-producing HepG2.2.15 cells and identified 49 proteins by mass
      spectrometry that are potentially associated with HBx. Two of the key proteins of
      the caspase-independent apoptosis pathway were newly identified, apoptosis
      inducing factor (AIF) and the homologous AMID (AIF-homologue mitochondrion
      associated inducer of death). We confirmed the interactions of HBx with AIF and
      with AMID by reciprocal coimmunoprecipitation experiments, respectively. We
      observed the expression of HBx-reduced AIF-mediated apoptosis and HBx
      colocalization with AIF and AMID, principally in the cytoplasm. Furthermore, the
      elevated cytoplasmic levels of HBx could inhibit mitochondrion-to-nucleus
      translocation of AIF. Here, we present the first detailed molecular evidence that
      HBx can repress apoptosis via inhibition of the caspase-independent apoptosis
      pathway. This inhibition of apoptosis involves the repression of the
      mitochondrion-to-nucleus translocation of AIF, although tests with AMID were not
      conclusive. These findings provide important insights into the new mechanism of
      the apoptosis inhibition by HBV.

PMID- 22871132
TI  - Sexual behaviour and risk factors for the acquisition of human papillomavirus
      infections in young people in Italy: suggestions for future vaccination policies.
AB  - BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted
      infection. The main risk factors correlated with HPV infection are: early sexual
      debut, the number of partners, frequency and type of sexual contact and partner's
      sexual histories.We surveyed sexual habits among young people in order to provide
      information that might orient decision-makers in adopting HPV multi-cohort
      vaccination policies. METHODS: We administered a questionnaire to students (14-24
      years old) in five Italian cities. RESULTS: 7298 questionnaires were analyzed
      (4962 females and 2336 males); 55.3% of females (95% CI 53.9-56.7) and 52.5% of
      males (95% CI 50.5-54.5) reported regular sexual activity. The mean age at sexual
      debut was 15.7 +/- 1.6 and 15.6 +/- 1.6 for females and males, respectively, and
      the median age was 16 for both sexes.With regard to contraceptive use during the
      last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of
      males and 42.8% of females used condoms. CONCLUSION: The results reveal
      precocious sexual activity among respondents, with the mean age at first
      intercourse declining as age decreases. Condom use proved to be scant.
      Considering lifestyle-related risk factors, males appear to have a higher
      probability of acquiring HPV infection than females.These data support the
      importance of promoting multi-cohort HPV vaccination strategies for females up to
      25 years of age. It is essential to improve vaccination coverage through
      different broad-spectrum strategies, including campaigns to increase awareness of
      sexually transmitted diseases and their prevention.

PMID- 22871133
TI  - C-terminal trans,trans-muconic acid ethyl ester partial retro-inverso
      pseudopeptides as proteasome inhibitors.
AB  - The development of specific inhibitors of the proteasome represents an important
      opportunity for new drug therapies. The central role of the multicatalytic
      complex in the intracellular proteolysis mediated by ubiquitin-proteasome pathway
      goes to discovery many molecules able to selectively inhibits enzymatic active
      subsites. Now, we report synthesis and activity of a new partial retro-inverso
      oligopseudopeptide derivatives bearing a trans,trans-muconic acid ethyl ester
      pharmacophoric unit at the C-terminal. Some analogues selectively inhibited in uM
      range the caspase-like (C-L) activity in the beta1 subunit of the proteasome. 

PMID- 22871134
TI  - Design, synthesis and evaluation of new thiazole-piperazines as
      acetylcholinesterase inhibitors.
AB  - In this study, some new 2-(4-substituted piperazine-1-yl)-N-[4-(2-methylthiazol-4
      yl)phenyl]acetamide derivatives were synthesized. The synthesized compounds were
      screened for their anticholinesterase activity on acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) enzymes by in vitro Ellman's method. The structural
      elucidation of the compounds was performed by using IR, (1)H-NMR, (13)C-NMR and
      FAB(+)-MS spectral data and elemental analyses results. Biological assays
      revealed that at 0.1 uM concentration, the most active compounds against AChE
      were 5n, 5o and 5p that indicated 96.44, 99.83 and 89.70% inhibition rates,
      respectively. Besides, IC50 value of the compound 5o was determined as 0.011 uM,
      whereas IC50 value of standard drug donepezil was 0.054 uM. The synthesized
      compounds did not show any notable inhibitory activity against BChE. 

PMID- 22871135
TI  - Evaluation of new antimicrobial agents on Bacillus spp. strains: docking affinity
      and in vitro inhibition of glutamate-racemase.
AB  - Three glutamic acid derivatives, two boron-containing and one imide-containing
      compound, were synthesized and tested for antimicrobial activity targeting
      glutamate-racemase. Antimicrobial effect was evaluated over Bacillus spp. Docking
      analysis shown that the test compounds bind near the active site of racemase
      isoforms, suggesting an allosteric effect. The boron derivatives had greater
      affinity than the imide derivative. In vitro assays shown good antimicrobial
      activity for the boron-containing compounds, and no effectiveness for the imide
      containing compounds. The minimum inhibitory concentration of tetracycline, used
      as standard, was lower than that of the boron-containing derivatives. However, it
      seems that the boron-containing derivatives are more selective for bacteria.
      Experimental evidence suggests that the boron-containing derivatives act by
      inhibiting the racemase enzyme. Therefore, these test compounds probably impede
      the formation of the bacterial cell wall. Thus, the boron-containing glutamic
      acid derivatives should certainly be of interest for future studies as
      antimicrobial agents for Bacillus spp. 

PMID- 22871136
TI  - Investigating the relationships between autobiographical remembering, the self
      and posttraumatic stress disorder in individuals with HIV.
AB  - A bidirectional relationship is proposed between the self and memory whereby
      autobiographical memories develop, express and maintain the self and the self
      implements control over autobiographical remembering (Conway, 2005). The
      objective of this study was to investigate the relationships between self
      concept, autobiographical remembering and posttraumatic stress disorder symptoms
      (PTSD) in individuals with HIV living in Iran. Participants were individuals with
      HIV (n = 61) and healthy nontrauma-exposed controls (n = 59). Participants
      completed Farsi versions of the Autobiographical Memory Test, Autobiographical
      Memory Interview, the "I AM" task and the Impact of Event-Revised. It was found
      that the HIV group provided fewer specific memories, had reduced semantic and
      episodic recall and provided fewer self-statements than the control group.
      Reduced autobiographical memory specificity was significantly correlated with
      recalling fewer self-statements and deficits in episodic memory mediated the
      relationship between group and fewer self-statements provided. Finally,
      proportion of HIV-themed self-statements correlated significantly with reduced
      memory specificity when age and education were included as covariates. The
      findings are discussed in regards to current psychological models of self and
      memory.

PMID- 22871137
TI  - Effects of chronic sub-lethal oxidative stress on biofilm formation by
      Azotobacter vinelandii.
AB  - This work showed that perturbations of the physiological steady-state level of
      reactive oxygen species (ROS) affected biofilm genesis and the characteristics of
      the model bacterium Azotobacter vinelandii. To get a continuous endogenous source
      of ROS, a strain exposed to chronic sub-lethal oxidative stress was deprived of
      the gene coding for the antioxidant rhodanese-like protein RhdA (MV474). In this
      study MV474 biofilm showed (i) a seven-fold higher growth rate, (ii) induction of
      catalase and alkyl-hydroxyl-peroxidase enzymes, (iii) higher average thicknesses
      due to increased production of a polysaccharide-rich extracellular matrix and
      (iv) less susceptibility to hydrogen peroxide than the wild-type strain (UW136).
      MV474 showed increased swimming and swarming activity and the swarming colonies
      experienced a higher level of oxidative stress compared to UW136. A continuous
      exogenous source of ROS increased biofilm formation in UW136. Overall, chronic
      sub-lethal oxidative events promoted sessile behavior in A. vinelandii.

PMID- 22871138
TI  - Systemic sclerosis with thrombotic thrombocytopenia purpura and malignant
      hypertension.
AB  - Thrombotic thrombocytopenia purpura (TTP) is a rare clinical syndrome
      characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia,
      neurologic symptoms, acute renal impairment, and fever. It has been seldom
      reported in systemic sclerosis (SSc). Systemic renal crisis is an infrequent
      complication of SSc, and is characterized by new onset malignant hypertension,
      rapidly progressive oliguric renal failure, and MAHA. In this study, we present a
      case of SSc of 1 month duration, with TTP accompanied by new onset malignant
      hypertension. The patient responded to plasmapheresis but still died of septic
      shock.

PMID- 22871139
TI  - Secretory carcinoma of the mammary gland in an 8-year-old Holstein-Friesian dairy
      cow.

PMID- 22871141
TI  - Gelucire 44/14 based immediate release formulations for poorly water-soluble
      drugs.
AB  - Here, we aim to evaluate Gelucire 44/14 as non-ionic surface-active excipient to
      produce immediate-release solid dosage forms for poorly water-soluble drugs.
      Gelucires are polyethylene glycol (PEG) glycerides composed of mono-, di- and
      triglycerides and mono- and diesters of PEG. They are inert semi-solid waxy
      amphiphilic excipients with surface-active properties that spontaneously form a
      fine dispersion or emulsion upon contact with water. Monolithic Gelucire 44/14
      structures are prone to prolonged erosion times, thereby slowing down drug
      dissolution. To overcome this issue, we combine either granulation or spray
      drying, followed by compression into tablets, with an optimized composition of
      disintegration promoting agents. This formulation strategy allows obtaining
      nearly 100% drug release within 10 min dissolution time.

PMID- 22871140
TI  - Iron(III)-doped, silica nanoshells: a biodegradable form of silica.
AB  - Silica nanoparticles are being investigated for a number of medical applications;
      however, their use in vivo has been questioned because of the potential for
      bioaccumulation. To obviate this problem, silica nanoshells were tested for
      enhanced biodegradability by doping iron(III) into the nanoshells. Exposure of
      the doped silica to small molecule chelators and mammalian serum was explored to
      test whether the removal of iron(III) from the silica nanoshell structure would
      facilitate its degradation. Iron chelators, such as EDTA, desferrioxamine, and
      deferiprone, were found to cause the nanoshells to degrade on the removal of
      iron(III) within several days at 80  degrees C. When the iron(III)-doped, silica
      nanoshells were submerged in fetal bovine and human serums at physiological
      temperature, they also degrade via removal of the iron by serum proteins, such as
      transferrin, over a period of several weeks.

PMID- 22871142
TI  - A simple and efficient transient transformation for hybrid aspen (Populus tremula
      * P. tremuloides).
AB  - BACKGROUND: The genus Populus is accepted as a model system for molecular tree
      biology. To investigate gene functions in Populus spp. trees, generating stable
      transgenic lines is the common technique for functional genetic studies. However,
      a limited number of genes have been targeted due to the lengthy transgenic
      process. Transient transformation assays complementing stable transformation have
      significant advantages for rapid in vivo assessment of gene function. The aim of
      this study is to develop a simple and efficient transient transformation for
      hybrid aspen and to provide its potential applications for functional genomic
      approaches. RESULTS: We developed an in planta transient transformation assay for
      young hybrid aspen cuttings using Agrobacterium-mediated vacuum infiltration. The
      transformation conditions such as the infiltration medium, the presence of a
      surfactant, the phase of bacterial growth and bacterial density were optimized to
      achieve a higher transformation efficiency in young aspen leaves. The
      Agrobacterium infiltration assay successfully transformed various cell types in
      leaf tissues. Intracellular localization of four aspen genes was confirmed in
      homologous Populus spp. using fusion constructs with the green fluorescent
      protein. Protein-protein interaction was detected in transiently co-transformed
      cells with bimolecular fluorescence complementation technique. In vivo promoter
      activity was monitored over a few days in aspen cuttings that were transformed
      with luciferase reporter gene driven by a circadian clock promoter. CONCLUSIONS:
      The Agrobacterium infiltration assay developed here is a simple and enhanced
      throughput method that requires minimum handling and short transgenic process.
      This method will facilitate functional analyses of Populus genes in a homologous
      plant system.

PMID- 22871143
TI  - Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid
      resistant Anopheles arabiensis from South-Western Ethiopia.
AB  - BACKGROUND: The emergence and spread of insecticide resistance in the major
      African malaria vectors Anopheles gambiae s.s. and Anopheles arabiensis may
      compromise control initiatives based on insecticide-treated nets (ITNs) or indoor
      residual spraying (IRS), and thus threaten the global malaria elimination
      strategy. METHODS: We investigated pyrethroid resistance in four populations of
      An. arabiensis from south-western Ethiopia and then assessed the bio-efficacy of
      six World Health Organization recommended long lasting insecticidal nets (LLINs)
      using these populations. RESULTS: For all four populations of An. arabiensis,
      bottle bioassays indicated low to moderate susceptibility to deltamethrin
      (mortality at 30 minutes ranged between 43 and 80%) and permethrin (mortality
      ranged between 16 and 76%). Pre-exposure to the synergist piperonylbutoxide (PBO)
      significantly increased the susceptibility of all four populations to both
      deltamethrin (mortality increased between 15.3 and 56.8%) and permethrin
      (mortality increased between 11.6 and 58.1%), indicating the possible involvement
      of metabolic resistance in addition to the previously identified kdr mutations.
      There was reduced susceptibility of all four An. arabiensis populations to the
      five standard LLINs tested (maximum mortality 81.1%; minimum mortality 13.9%).
      Bio-efficacy against the four populations varied by net type, with the largest
      margin of difference observed with the Jimma population (67.2% difference).
      Moreover, there were differences in the bio-efficacy of each individual standard
      LLIN against the four mosquito populations; for example there was a difference of
      40% in mortality of Yorkool against two populations. Results from standard LLINs
      indicated reduced susceptibility to new, unused nets that was likely due to
      observed pyrethroid resistance. The roof of the combination LLIN performed
      optimally (100% mortality) against all the four populations of An. arabiensis,
      indicating that observed reductions in susceptibility could be ameliorated with
      the combination of PBO with deltamethrin, as used in PermaNet(r) 3.0. CONCLUSION:
      Our results suggest that bio-efficacy evaluations using local mosquito
      populations should be conducted where possible to make evidence-based decisions
      on the most suitable control products, and that those combining multiple
      chemicals such as PBO and deltamethrin should be considered for maintaining a
      high level of efficacy in vector control programmes.

PMID- 22871144
TI  - Transfer-free electrical insulation of epitaxial graphene from its metal
      substrate.
AB  - High-quality, large-area epitaxial graphene can be grown on metal surfaces, but
      its transport properties cannot be exploited because the electrical conduction is
      dominated by the substrate. Here we insulate epitaxial graphene on Ru(0001) by a
      stepwise intercalation of silicon and oxygen, and the eventual formation of a
      SiO(2) layer between the graphene and the metal. We follow the reaction steps by
      X-ray photoemission spectroscopy and demonstrate the electrical insulation using
      a nanoscale multipoint probe technique.

PMID- 22871145
TI  - Barriers to breastfeeding in a resident clinic.
AB  - Despite the known health benefits for mother and infant, compliance with
      exclusive breastfeeding continues to challenge many healthcare providers. In an
      ongoing attempt to maintain the goals of the Healthy People 2010 initiative, our
      institution set out to identify patients with suboptimal breastfeeding rates in
      order to recognize potential barriers. Review of breastfeeding rates at the time
      of discharge noted significantly lower participation by clinic patients. In order
      to develop successful interventions, the aim of this study was to survey clinic
      patients to determine their intentions, attitudes, and obstacles to the practice
      of exclusive breastfeeding. In total, 188 surveys were completed during a 2-month
      time period. Respondents were primarily Hispanic (76.4% vs. 9.6% black and 8.4%
      white) and multiparous (57.5%) with a mean age of 25.7 years (range, 15-39 years
      old). Although 95.3% of respondents indicated that they believed breastmilk
      provided adequate nutrition, only 35.3% planned on exclusively breastfeeding.
      Access to free formula through the Special Supplemental Nutrition Program for
      Women, Infants and Children was the most common reason not to breastfeed (48.3%),
      followed by fear of pain and the need to return to work/school. Patients reported
      that the person with the greatest influence on their decision to breastfeed was
      their partner/spouse. Access to a lactation counselor was the most popular
      intervention requested, even among experienced multiparous patients (78.9% of
      whom had previously breastfed). In conclusion, the survey indicated that planned
      exclusive breastfeeding rates are low among this inner-city resident clinic and
      interventions should include involvement of the partners/spouses and access to
      lactational support.

PMID- 22871146
TI  - Biosynthesis and properties of medium-chain-length polyhydroxyalkanoates with
      enriched content of the dominant monomer.
AB  - When grown in a nonanoic acid-limited chemostat at a dilution rate of 0.25 h(-1),
      Pseudomonas putida KT2440 produced poly(3-hydroxynonanoate-co-3
      hydroxyheptanoate) containing 68 mol % 3-hydroxynonanoate (C9) and 32 mol % 3
      hydroxyheptanoate (C7). Under the same conditions, but in the presence of acrylic
      acid, a fatty acid beta-oxidation inhibitor, the C9 monomer content increased to
      88 mol %. Cofeeding glucose (3.9 g L(-1)) and nonanoic acid (2.9 +/- 0.1 g L(-1))
      in continuous culture with 0.2 g L(-1) of acrylic acid in the feed, further
      increased the C9 content to 95 mol %. A yield of PHA from nonanoic acid of 0.93
      mol mol(-1) was attained. PHA with a 3-hydroxyoctanoate (C8) content of 98 mol %
      was produced with the same cofeeding methodology from octanoic acid. As the
      dominant monomer content increased, the melting point of the poly(3
      hydroxynonanoate) copolymers increased from 46 to 63  degrees C and that of the
      poly(3-hydroxyoctanoate) copolymers from 54 to 62  degrees C. All copolymer
      compositions resulted in elongation to break values of about 1300%, but tensile
      strength at break and Young's modulus both increased with increasing amounts of
      the dominant monomer.

PMID- 22871147
TI  - DJ-1 promotes the proteasomal degradation of Fis1: implications of DJ-1 in
      neuronal protection.
AB  - Mutations in DJ-1/PARK7 (Parkinson protein 7) have been identified as a cause of
      autosomal-recessive PD (Parkinson's disease) and the antioxidant property of DJ-1
      has been shown to be involved in the regulation of mitochondrial function and
      neuronal cell survival. In the present study, we first found that the DJ-1
      transgene mitigated MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced
      DA (dopamine) neuron cell death and cell loss. We then observed that the protein
      levels of DJ-1 were significantly decreased, whereas levels of Fis1 [fission 1
      (mitochondrial outer membrane) homologue] were noticeably increased in the
      striatum of MPTP-treated mice. In addition to our identification of RNF5 (RING
      finger protein-5) as an E3-ligase for Fis1 ubiquitination, we demonstrated the
      involvement of the DJ-1/Akt/RNF5 signalling pathway in the regulation of Fis1
      proteasomal degradation. In other experiments, we found that Akt1 enhances the
      mitochondrial translocation and E3-ligase activity of RNF5, leading to Fis1
      degradation. Together, the identification of Fis1 degradation by DJ-1 signalling
      in the regulation of oxidative stress-induced neuronal cell death supplies a
      novel mechanism of DJ-1 in neuronal protection with the implication of DJ-1 in a
      potential therapeutic avenue for PD.

PMID- 22871148
TI  - Solid-supported NOTA and DOTA chelators useful for the synthesis of 3'
      radiometalated oligonucleotides.
AB  - Esterified precursors of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      (DOTA; 18) and 1,4,7-triazacyclononane-1,4,7-trisacetic acid (NOTA; 17,19)
      ligands bearing a dimethoxytritylated hydroxyl side arm were prepared and
      immobilized via an ester linkage to long chain alkyl amine derivatized controlled
      pore glass (LCAA-CPG). Oligonucleotide chains were then assembled on the hydroxyl
      function and conjugates were released and deprotected by a two-step cleavage with
      aqueous alkali and ammonia. The 3'-DOTA and 3'-NOTA conjugated oligonucleotides
      were converted to (68)Ga chelates by a brief treatment with [(68)Ga]Cl(3) at
      elevated temperature. Applicability of the conjugates for in vivo imaging with
      positron emission tomography (PET) was verified.

PMID- 22871149
TI  - Oxygen uptake and heart rate response of 6 standardized tennis drills.
AB  - The purpose of this study was to compare the oxygen uptake of various on-court
      tennis drills. Eleven tennis players were monitored with a portable metabolic
      device to measure oxygen uptake of 6 different tennis drills at low and high
      speeds. The 6 drills were done with or without striking the ball, over half or
      full-width of the court, in attack or defense mode, using forehand or backhand
      strokes. Oxygen uptake values (mean +/- SD) ranged from 33.8 +/- 4.2 to 42.3 +/-
      5.1 mL.kg-1.min-1 when running at low speed on the full-width court in defense
      mode without striking the ball and when running at high speed on the full-width
      court in attack mode while striking the ball, respectively. Specific differences
      were observed. Attacking mode requires 6.5% more energy than defensive playing
      mode. Backhand strokes demand 7% more energy at low speed than forehand ones.
      Running and striking the ball costs 10% more energy than running without striking
      the ball. While striking the ball, shuttle running on half-width court costs 14%
      more energy than running on full-width courts. The specificity of the oxygen
      uptake responses obtained for these various tennis drills gives an improved
      representation of their energy cost and could be used to optimize training loads.

PMID- 22871150
TI  - Gadolinium in pediatric cardiovascular magnetic resonance: what we know and how
      we practice.
AB  - BACKGROUND: The association of gadolinium-based contrast agents (GBCAs) with
      nephrogenic systemic fibrosis (NSF) has led to a heightened awareness towards
      patients' renal function. Whereas detailed guidelines exist for the use of GBCAs
      in adult patients, best practice is less well defined in children, especially in
      the very young. We aimed at identifying current practice with regards to the use
      of GBCAs in children who undergo cardiovascular magnetic resonance. METHODS: We
      conducted a worldwide survey among cardiac imagers with pediatric expertise. The
      questionnaire contained 21 questions covering the imagers' work environments,
      GBCAs used, monitoring of renal function, and a special emphasis was placed on
      the practice in neonates. RESULTS: The survey yielded 70 replies. The single most
      commonly used GBCA was gadopentetate dimeglumine 34/70 (49%). Among the
      respondents, the choice of GBCA was more importantly based on availability 26/70
      (37%) and approval by a pharmaceutical licensing body that most closely reflects
      the indication 16/70 (23%) than image quality 7/70 (10%) and side effect profile
      8/70 (11%). 55/70 (79%) of respondents performed scans in neonates <1 week of age
      and 52/55 (95%) of them used GBCA in neonates. 65/70 (93%) respondents at least
      assess some of their patients' renal functions. Formula-based estimate of
      glomerular filtration rate is the most popular assessment method 35/65 (54%). In
      patients with a glomerular filtration rate < 30 ml/min/1.73 m(2) 62/70 (89%) of
      respondents do not administer gadolinium at all. The single most common side
      effect of gadolinium was noted to be nausea/emesis 34/57 (60%) followed by
      discomfort at injection site 17/57 (30%). CONCLUSIONS: Cardiac imagers are aware
      of the immature renal function and physiological differences of their pediatric
      patients that place them at risk for NSF. Epidemiological data is needed for
      pediatric cardiovascular licensure of gadolinium compounds and for the creation
      of practice guidelines which will replace current-day practice based on
      individual clinical judgment.

PMID- 22871151
TI  - Evidence of cryptic introgression in tomato (Solanum lycopersicum L.) based on
      wild tomato species alleles.
AB  - BACKGROUND: Many highly beneficial traits (e.g. disease or abiotic stress
      resistance) have been transferred into crops through crosses with their wild
      relatives. The 13 recognized species of tomato (Solanum section Lycopersicon) are
      closely related to each other and wild species genes have been extensively used
      for improvement of the crop, Solanum lycopersicum L. In addition, the lack of
      geographical barriers has permitted natural hybridization between S. lycopersicum
      and its closest wild relative Solanum pimpinellifolium in Ecuador, Peru and
      northern Chile. In order to better understand patterns of S. lycopersicum
      diversity, we sequenced 47 markers ranging in length from 130 to 1200 bp (total
      of 24 kb) in genotypes of S. lycopersicum and wild tomato species S.
      pimpinellifolium, Solanum arcanum, Solanum peruvianum, Solanum pennellii and
      Solanum habrochaites. Between six and twelve genotypes were comparatively
      analyzed per marker. Several of the markers had previously been hypothesized as
      carrying wild species alleles within S. lycopersicum, i.e., cryptic
      introgressions. RESULTS: Each marker was mapped with high confidence (e<1 x 10
      30) to a single genomic location using BLASTN against tomato whole genome shotgun
      chromosomes (SL2.40) database. Neighbor-joining trees showed high mean bootstrap
      support (86.8 +/- 2.34%) for distinguishing red-fruited from green-fruited taxa
      for 38 of the markers. Hybridization and parsimony splits networks, genomic map
      positions of markers relative to documented introgressions, and historical
      origins of accessions were used to interpret evolutionary patterns at nine
      markers with putatively introgressed alleles. CONCLUSION: Of the 47 genetic
      markers surveyed in this study, four were involved in linkage drag on chromosome
      9 during introgression breeding, while alleles at five markers apparently
      originated from natural hybridization with S. pimpinellifolium and were
      associated with primitive genotypes of S. lycopersicum. The positive
      identification of introgressed genes within crop species such as S. lycopersicum
      will help inform conservation and utilization of crop germplasm diversity, for
      example, facilitating the purging of undesirable linkage drag or the exploitation
      of novel, favorable alleles.

PMID- 22871152
TI  - Two-compartment toxicokinetic-toxicodynamic model to predict metal toxicity in
      Daphnia magna.
AB  - Relating the toxicity of metals to their internal concentration is difficult due
      to complicated detoxification processes within organisms. Only the metabolically
      available metals are potentially toxic to organisms, while metals in the
      detoxified form are toxicologically irrelevant. Accordingly, we developed a two
      compartment toxicokinetic-toxicodynamic model for metals in a freshwater
      cladoceran, Daphnia magna. The toxicokinetics simulated the bioaccumulation
      processes, while the toxicodynamics quantitatively described the corresponding
      processes of toxicity development. Model parameters were estimated for D. magna
      and three metals, i.e., cadmium, zinc, and mercury, by fitting the literature
      data on metal bioaccumulation and toxicity. A range of crucial information for
      toxicity prediction can be readily derived from the model, including
      detoxification rate, no-effect concentration, threshold influx rate for toxicity,
      and maximum duration without toxicity. This process-based model is flexible and
      can help improve ecological risk assessments for metals.

PMID- 22871153
TI  - Physical activity and health related quality of life.
AB  - BACKGROUND: Research on the relationship between Health Related Quality of Life
      (HRQoL) and physical activity (PA), to date, have rarely investigated how this
      relationship differ across objective and subjective measures of PA. The aim of
      this paper is to explore the relationship between HRQoL and PA, and examine how
      this relationship differs across objective and subjective measures of PA, within
      the context of a large representative national survey from England. METHODS:
      Using a sample of 5,537 adults (40-60 years) from a representative national
      survey in England (Health Survey for England 2008), Tobit regressions with upper
      censoring was employed to model the association between HRQoL and objective, and
      subjective measures of PA controlling for potential confounders. We tested the
      robustness of this relationship across specific types of PA. HRQoL was assessed
      using the summary measure of health state utility value derived from the EuroQol
      5 Dimensions (EQ-5D) whilst PA was assessed via subjective measure
      (questionnaire) and objective measure (accelerometer-actigraph model GT1M). The
      actigraph was worn (at the waist) for 7 days (during waking hours) by a randomly
      selected sub-sample of the HSE 2008 respondents (4,507 adults--16 plus years),
      with a valid day constituting 10 hours. Analysis was conducted in 2010. RESULTS:
      Findings suggest that higher levels of PA are associated with better HRQoL
      (regression coefficient: 0.026 to 0.072). This relationship is consistent across
      different measures and types of PA although differences in the magnitude of HRQoL
      benefit associated with objective and subjective (regression coefficient: 0.047)
      measures of PA are noticeable, with the former measure being associated with a
      relatively better HRQoL (regression coefficient: 0.072). CONCLUSION: Higher
      levels of PA are associated with better HRQoL. Using an objective measure of PA
      compared with subjective shows a relatively better HRQoL.

PMID- 22871154
TI  - Emergency department ultrasonography guided long-axis antecubital intravenous
      cannulation: How to do it.
AB  - An 85-year-old woman with a past medical history of severe peripheral vascular
      disease and right below knee amputation presented to the emergency department
      with a 1-day history of non-positional dizziness and weakness. The patient
      required intravenous access to work up her dizziness and weakness. The patient
      had multiple failed blind ED peripheral IV attempts performed in the past.
      Emergency department bedside ultrasonography with a high frequency linear array
      vascular probe was used to guide antecubital brachial vein cannulation on the
      first attempt using the long-axis approach.

PMID- 22871155
TI  - Arabin cerclage pessary in the management of cervical insufficiency.
AB  - OBJECTIVE: To evaluate the use of Arabin cerclage pessary in the management of
      cervical insufficiency. METHODS: The pregnancy outcome of 20 women carrying
      singleton pregnancy referred for suspected cervical insufficiency and chose
      Arabin cerclage pessary for treatment from 2009-2011 were reviewed. Pregnancy
      outcome were analysed according to presence of risk factors, amniotic fluid
      sludge, cervical length and gestation at pessary insertion. RESULTS: At
      presentation, mean cervical length was 1.17 cm (range 0-2.33 cm), mean gestation
      at pessary insertion and delivery was 20.6 (12.9-26.1) weeks and 32.1 (14.7-40.1)
      weeks, respectively, and mean prolongation of pregnancy was 11.5 (0.5-25.2)
      weeks. Overall, 5 (25%) had fetal loss between 14.7-23.1 weeks, while 3 (15%) and
      12 (60%) delivered before and after 34 weeks gestation, respectively with no
      perinatal mortality. Compared with women with cervical length <1.5 cm, all those
      with cervical length >=1.5 cm had pregnancy prolonged for >=49 days (100 vs. 54%
      p = 0.032) and 86% delivered beyond 34 weeks (86 vs. 46% p = 0.085). CONCLUSIONS:
      Arabin cerclage pessary appears to be optimal for treating women at high risk of
      cervical insufficiency with a cervical length of 1.5-2.5 cm, while it is an
      acceptable option for high risk women with cervical length <1.5 cm.

PMID- 22871156
TI  - Depletion of acidic phosphopeptides by SAX to improve the coverage for the
      detection of basophilic kinase substrates.
AB  - The Ser/Thr protein kinases fall into three major subgroups, pro-directed,
      basophilic, and acidophilic, on the basis of the types of substrate sequences
      that they preferred. Despite many phosphoproteomics efforts that have been taken
      for global profiling of phosphopeptides, methodologies focusing on analyzing a
      particular type of kinase substrates have seldom been reported. Selective
      enrichment of phosphopeptides from basophilic kinase substrates is difficult
      because basophilic motifs are cleaved by trypsin during digestion. In this study,
      we develop a negative enrichment strategy to enhance the identification of
      basophilic kinase substrates. This method is based on an observation that high pH
      strong anion exchange (SAX) chromatography can separate tryptic phosphopeptides
      according to the number of acidic amino acidic residues that they have. Thus, SAX
      was applied to deplete acidic phosphopeptides from the phosphopeptide mixture,
      which improved the coverage for the detection of basophilic kinase substrates.
      The SAX depletion approach was further combined with online SCX-RP separation for
      large-scale analysis of mouse liver phosphoproteome, which resulted in the
      identification of 6944 phosphorylated sites. It was found that motifs associated
      with basophilic kinases prevail for these identified phosphorylated sites.

PMID- 22871157
TI  - Potential hazards associated with combustion of bio-derived versus petroleum
      derived diesel fuel.
AB  - Fuels from renewable resources have gained worldwide interest due to limited
      fossil oil sources and the possible reduction of atmospheric greenhouse gas. One
      of these fuels is so called biodiesel produced from vegetable oil by
      transesterification into fatty acid methyl esters (FAME). To get a first insight
      into changes of health hazards from diesel engine emissions (DEE) by use of
      biodiesel scientific studies were reviewed which compared the combustion of FAME
      with common diesel fuel (DF) for legally regulated and non-regulated emissions as
      well as for toxic effects. A total number of 62 publications on chemical analyses
      of DEE and 18 toxicological in vitro studies were identified meeting the
      criteria. In addition, a very small number of human studies and animal
      experiments were available. In most studies, combustion of biodiesel reduces
      legally regulated emissions of carbon monoxide, hydrocarbons, and particulate
      matter. Nitrogen oxides are regularly increased. Among the non-regulated
      emissions aldehydes are increased, while polycyclic aromatic hydrocarbons are
      lowered. Most biological in vitro assays show a stronger cytotoxicity of
      biodiesel exhaust and the animal experiments reveal stronger irritant effects.
      Both findings are possibly caused by the higher content of nitrogen oxides and
      aldehydes in biodiesel exhaust. The lower content of PAH is reflected by a weaker
      mutagenicity compared to DF exhaust. However, recent studies show a very low
      mutagenicity of DF exhaust as well, probably caused by elimination of sulfur in
      present DF qualities and the use of new technology diesel engines. Combustion of
      vegetable oil (VO) in common diesel engines causes a strongly enhanced
      mutagenicity of the exhaust despite nearly unchanged regulated emissions. The
      newly developed fuel "hydrotreated vegetable oil" (HVO) seems to be promising.
      HVO has physical and chemical advantages compared to FAME. Preliminary results
      show lower regulated and non-regulated emissions and a decreased mutagenicity.

PMID- 22871158
TI  - Synthesis, aqueous reactivity, and biological evaluation of carboxylic acid ester
      functionalized platinum-acridine hybrid anticancer agents.
AB  - The synthesis of platinum-acridine hybrid agents containing carboxylic acid ester
      groups is described. The most active derivatives and the unmodified parent
      compounds showed up to 6-fold higher activity in ovarian cancer (OVCAR-3) and
      breast cancer (MCF-7, MDA-MB-231) cell lines than cisplatin. Inhibition of cell
      proliferation at nanomolar concentrations was observed in pancreatic (PANC-1) and
      nonsmall cell lung cancer cells (NSCLC, NCI-H460) of 80- and 150-fold,
      respectively. Introduction of the ester groups did not affect the cytotoxic
      properties of the hybrids, which form the same monofunctional-intercalative DNA
      adducts as the parent compounds, as demonstrated in a plasmid unwinding assay. In
      line high-performance liquid chromatography and electrospray mass spectrometry
      (LC-ESMS) shows that the ester moieties undergo platinum-mediated hydrolysis in a
      chloride concentration-dependent manner to form carboxylate chelates. Potential
      applications of the chloride-sensitive ester hydrolysis as a self-immolative
      release mechanism for tumor-selective delivery of platinum-acridines are
      discussed.

PMID- 22871160
TI  - Working memory and the memory distortion component of hindsight bias.
AB  - One component of hindsight bias is memory distortion: Individuals' recollections
      of their predictions are biased towards known outcomes. The present study
      examined the role of working memory in the memory distortion component of
      hindsight bias. Participants answered almanac-like questions, completed a measure
      of working memory capacity, were provided with the correct answers, and attempted
      to recollect their original judgements in two conditions: with and without a
      concurrent working memory load. Participants' recalled judgements were more
      biased by feedback when they recalled these judgements with a concurrent memory
      load and working memory capacity was negatively correlated with memory
      distortion. These findings are consistent with reconstruction accounts of the
      memory distortion component of hindsight bias and, more generally, with dual
      process theories of cognition. These results also relate the memory distortion
      component of hindsight bias with other cognitive errors, such as source
      monitoring errors, the belief bias in syllogistic reasoning and anchoring
      effects. Implications for the separate components view of hindsight bias are
      discussed.

PMID- 22871159
TI  - Computational design of catalytic dyads and oxyanion holes for ester hydrolysis.
AB  - Nucleophilic catalysis is a general strategy for accelerating ester and amide
      hydrolysis. In natural active sites, nucleophilic elements such as catalytic
      dyads and triads are usually paired with oxyanion holes for substrate activation,
      but it is difficult to parse out the independent contributions of these elements
      or to understand how they emerged in the course of evolution. Here we explore the
      minimal requirements for esterase activity by computationally designing
      artificial catalysts using catalytic dyads and oxyanion holes. We found much
      higher success rates using designed oxyanion holes formed by backbone NH groups
      rather than by side chains or bridging water molecules and obtained four active
      designs in different scaffolds by combining this motif with a Cys-His dyad.
      Following active site optimization, the most active of the variants exhibited a
      catalytic efficiency (k(cat)/K(M)) of 400 M(-1) s(-1) for the cleavage of a p
      nitrophenyl ester. Kinetic experiments indicate that the active site cysteines
      are rapidly acylated as programmed by design, but the subsequent slow hydrolysis
      of the acyl-enzyme intermediate limits overall catalytic efficiency. Moreover,
      the Cys-His dyads are not properly formed in crystal structures of the designed
      enzymes. These results highlight the challenges that computational design must
      overcome to achieve high levels of activity.

PMID- 22871161
TI  - Three-dimensional pore-scale modelling of dentinal infiltration.
AB  - Dentine is the fundamental substrate of restorative dentistry, and its properties
      and characteristics are the key determinants of restorative processes. In
      contemporary restorative techniques, bonding to Dentine is created by the
      impregnation of the demineralised dentine by blends of resin monomers. In this
      paper, a numerical model of dentinal infiltration is proposed. The aim is to
      follow the resin front and to point out the optimal parameter set. The main tool
      is a level set technique to follow the evolving interface. It is coupled with the
      Navier-Stokes equation where capillary effect gives rise to the appearance of a
      new term in the variational approach than discretised by finite elements. Using
      an appropriate geometry representing demineralised dentine, the moving front is
      observed. First, a simulation of porosimetry test is achieved in order to
      validate the model. The two expected pore sizes are detected and the simulation
      also points out limitations of mercury intrusion porosimetry test in an
      educational way. Then a wetting fluid (representing the dental resin) is
      numerically infiltrated. In the dentinal porous network, capillarity is taken
      into account in our model by including a capillary term. A crucial conclusion is
      drawn from this study: resin application time by practitioners is sufficient if,
      in the infiltration process, the wetting phase is the resin. 

PMID- 22871162
TI  - Development of a virus neutralisation test to detect antibodies against
      Schmallenberg virus and serological results in suspect and infected herds.
AB  - BACKGROUND: At the end of 2011, a new orthobunyavirus, tentatively named
      Schmallenberg virus (SBV), was discovered in Germany. This virus has since been
      associated with clinical signs of decreased milk production, watery diarrhoea and
      fever in dairy cows, and subsequently also with congenital malformations in
      calves, lambs and goat kids. In affected countries, initial surveillance for the
      infection was based on examination of malformed progeny. These suspicions were
      followed up by real-time reverse transcription polymerase chain reaction (RT-PCR)
      on brain tissue. For epidemiological purposes, a serological assay was, however,
      needed. RESULTS: A virus neutralisation test (VNT) was developed and optimized,
      and subsequently evaluated. This VNT has a specificity of >99% and the
      sensitivity is likely also very close to 100%. The assay is highly repeatable and
      reproducible. The final assay was used to test for antibodies in cows, ewes and
      does from herds known to be infected or suspected to be so. Targets for sampling
      in these herds were the mothers of malformed offspring. In herds with an RT-PCR
      confirmed SBV infection, more than 94% (190 out of 201) of the ewes and 99% (145
      out of 146) of the cows were seropositive. In herds with suspicion of SBV
      infection based on birth of malformed offspring only (no or negative RT-PCR),
      more than 90% (231 out of 255) of the ewes and 95% (795 out of 834) of the cows
      were seropositive. In goats, on the other hand, only a low number of
      seropositives was found: overall 36.4%, being 16 out of 44 goats tested.
      CONCLUSIONS: Given the characteristics of this VNT, it can be used at a relative
      high throughput for testing of animals for export, surveillance, screening and
      research purposes, but can also be used as a confirmation test for commercially
      available enzyme-linked immunosorbent assays (ELISA's) and for (relative)
      quantification of antibodies.Suspicions of SBV infections that were confirmed by
      RT-PCR were almost always confirmed by serology in cows. Due to individual
      registration and identification of cows and calves, affected offspring could
      almost always be traced back to the mother. Ewes on the other hand were not
      always the mothers of affected lambs, but were in many cases herd mates with
      unaffected lambs. This indicated a high within-herd seroprevalence of antibodies
      against SBV.

PMID- 22871163
TI  - Use of a peptide enhancing the ability of radiation therapy to kill cancer cells:
      a patent evaluation of WO2012016918.
AB  - BACKGROUND: Faulty apoptosis is a known mechanism that leads to resistance to
      radiotherapy. The application (WO2012016918A1) deals with a peptide useful for
      disrupting this resistance mechanism and enhancing the efficiency of
      radiotherapy. METHODS: A peptide consisting essentially of the N2 sequence of the
      RasGAP protein is conjugated to the HIV-TAT(48-57) cell permeation sequence. The
      DNA sequence encoding the peptide (TAT-RasGAP(317-326)) is synthesized and
      introduced into the host cells. RESULTS: TAT-RasGAP(317-326) is demonstrated to
      potentiate the efficacy of gamma-irradiation-mediated cell killing both in tumor
      cell lines and in mouse tumor models, disregarding the status of p53, but not in
      non-cancer cells. CONCLUSION: TAT-RasGAP(317-326) peptide favors apoptosis of
      tumor cells, but not normal cells in response to radiotherapy. The invention
      provides a specific method that is probably to be used in cancers that are radio
      resistant.

PMID- 22871164
TI  - Smooth muscle cells isolated from thoracic aortic aneurysms exhibit increased
      genomic damage, but similar tendency for apoptosis.
AB  - Aortic aneurysms (AA) are characterized by structural deterioration leading to
      progressive dilation. During the development of AA, two key structural changes
      are pronounced, one being degradation of extracellular matrix and the other loss
      of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS)
      are produced above physiological levels in dilated (aneurismal) part of the aorta
      compared to the nondilated part and they are known to be associated with both the
      extracellular matrix degradation and the loss of SMCs. In this study, we
      hypothesized that aneurismal SMCs are more prone to apoptosis and that at least
      some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this
      hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared
      their apoptotic tendency with normal SMCs in response to H(2)O(2), oxidized
      sterol, or UV treatment. Exposed cells exhibited morphological changes
      characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin
      condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP
      nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in
      these cells. Vascular SMCs were analyzed for their micronuclei (MN) and
      binucleate (BN) frequency as indicators of genomic abnormality. These data were
      then compared to patient parameters, including age, gender, hypertension, or
      aortic diameter for existing correlations. While the tendency for apoptosis was
      not significantly different compared to normal cells, both the %MN and %BN were
      higher in aneurismal SMCs. The data suggest that there is increased DNA damage in
      TAA samples, which might play a pivotal role in disease development.

PMID- 22871166
TI  - Interface formation in monolayer graphene-boron nitride heterostructures.
AB  - The ability to control the formation of interfaces between different materials
      has become one of the foundations of modern materials science. With the advent of
      two-dimensional (2D) crystals, low-dimensional equivalents of conventional
      interfaces can be envisioned: line boundaries separating different materials
      integrated in a single 2D sheet. Graphene and hexagonal boron nitride offer an
      attractive system from which to build such 2D heterostructures. They are
      isostructural, nearly lattice-matched, and isoelectronic, yet their different
      band structures promise interesting functional properties arising from their
      integration. Here, we use a combination of in situ microscopy techniques to study
      the growth and interface formation of monolayer graphene-boron nitride
      heterostructures on ruthenium. In a sequential chemical vapor deposition process,
      boron nitride grows preferentially at the edges of existing monolayer graphene
      domains, which can be exploited for synthesizing continuous 2D membranes of
      graphene embedded in boron nitride. High-temperature growth leads to intermixing
      near the interface, similar to interfacial alloying in conventional
      heterostructures. Using real-time microscopy, we identify processes that
      eliminate this intermixing and thus pave the way to graphene-boron nitride
      heterostructures with atomically sharp interfaces.

PMID- 22871165
TI  - An asymmetric synthesis of 1,2,4-trioxane anticancer agents via desymmetrization
      of peroxyquinols through a Bronsted acid catalysis cascade.
AB  - The desymmetrization of p-peroxyquinols using a Bronsted acid-catalyzed
      acetalization/oxa-Michael cascade was achieved in high yields and selectivities
      for a variety of aliphatic and aryl aldehydes. Mechanistic studies suggest that
      the reaction proceeds through a dynamic kinetic resolution of the peroxy
      hemiacetal intermediate. The resulting 1,2,4-trioxane products were derivatized
      and show potent cancer cell-growth inhibition.

PMID- 22871167
TI  - Aromatic amide foldamers: structures, properties, and functions.

PMID- 22871168
TI  - A probabilistic framework for peptide and protein quantification from data
      dependent and data-independent LC-MS proteomics experiments.
AB  - A probability-based quantification framework is presented for the calculation of
      relative peptide and protein abundance in label-free and label-dependent LC-MS
      proteomics data. The results are accompanied by credible intervals and regulation
      probabilities. The algorithm takes into account data uncertainties via Poisson
      statistics modified by a noise contribution that is determined automatically
      during an initial normalization stage. Protein quantification relies on
      assignments of component peptides to the acquired data. These assignments are
      generally of variable reliability and may not be present across all of the
      experiments comprising an analysis. It is also possible for a peptide to be
      identified to more than one protein in a given mixture. For these reasons the
      algorithm accepts a prior probability of peptide assignment for each intensity
      measurement. The model is constructed in such a way that outliers of any type can
      be automatically reweighted. Two discrete normalization methods can be employed.
      The first method is based on a user-defined subset of peptides, while the second
      method relies on the presence of a dominant background of endogenous peptides for
      which the concentration is assumed to be unaffected. Normalization is performed
      using the same computational and statistical procedures employed by the main
      quantification algorithm. The performance of the algorithm will be illustrated on
      example data sets, and its utility demonstrated for typical proteomics
      applications. The quantification algorithm supports relative protein
      quantification based on precursor and product ion intensities acquired by means
      of data-dependent methods, originating from all common isotopically-labeled
      approaches, as well as label-free ion intensity-based data-independent methods.

PMID- 22871169
TI  - Breastfeeding in women with severe preeclampsia.
AB  - BACKGROUND: In the United States, breastfeeding initiation is reported for 75% of
      all live births; however, little information is available for mothers affected by
      severe preeclampsia (SP) who because of magnesium sulfate treatment are separated
      from their infants in the immediate postpartum period. This study examined
      feeding practices and factors associated with breastfeeding initiation in 281
      women with SP and their 200 late-preterm and 81 term infants. SUBJECTS AND
      METHODS: SP was diagnosed according to established clinical and laboratory
      criteria. Infant feeding preference was ascertained on admission to labor and
      delivery. Variables known to influence breastfeeding initiation, including
      maternal age, smoking, obesity, and racial and educational characteristics, were
      assessed. RESULTS: All mothers received magnesium sulfate for 24 hours following
      delivery. Of 281 infants, 54% were admitted to the neonatal intensive care unit
      (NICU). All mothers and infants survived. On admission, 149 women intended to
      breastfeed, 73 intended to feed formula, and 59 were undecided. Four of 73 women
      who did not wish to breastfeed and 27 of 59 originally undecided later initiated
      breastfeeding. At discharge, 144 (51%) of all these mothers had successfully
      initiated breastfeeding. Factors associated with breastfeeding initiation failure
      included African American race, younger age, lower education, multiparity,
      smoking, and obesity. Of 149 women who intended to breastfeed, 76% were
      successful, and logistic regression analysis showed that intention to breastfeed
      was the most significant predictor of breastfeeding initiation. During the first
      24 hours postpartum, 78% of infants receiving well-baby care, and 4% of those
      admitted to the NICU visited with their mother once. Among women who intended to
      breastfeed, successful breastfeeding initiation involved 85% of infants receiving
      routine well-baby care and 69% of those admitted to the NICU. CONCLUSIONS: In
      spite of the challenges created by SP, including early maternal separation,
      breastfeeding initiation is possible. The strongest predictor for breastfeeding
      success remains the intention to breastfeed, whereas race, lower level of
      education, and obesity are associated with breastfeeding initiation failure.

PMID- 22871170
TI  - Regulation and physiologic functions of GTPases in mitochondrial fusion and
      fission in mammals.
AB  - SIGNIFICANCE: Mitochondria are double membrane-bound organelles with tubular
      network structures that are essential for oxidative ATP production and play
      pivotal roles in regulating calcium homeostasis and apoptosis. Furthermore,
      mitochondria produce large amounts of reactive oxygen species that are fatal to
      cellular functions through uncoupled respiration. These organelles dynamically
      change their morphology by frequent fusion and fission, and three types of high
      molecular weight GTPase proteins have been identified as core components of the
      fusion and fission machineries. RECENT ADVANCES: Here, we review recent advances
      in the study of mitochondrial fission and fusion GTPases and their physiologic
      roles in mammalian cells. The regulation of mitochondrial dynamics coupled with a
      quality control system is essential for cellular homeostasis, development, and
      tissue differentiation. Defects of these mechanisms cause various disorders,
      including neurodegenerative diseases, such as Parkinson's disease, Huntington's
      disease, and Alzheimer's disease. CRITICAL ISSUES: Although a significant amount
      of relevant data has accumulated on the regulation of mammalian mitochondrial
      fusion and fission, mechanistic molecular details and cellular functions still
      remain insufficiently defined. FUTURE DIRECTIONS: Elucidating the physiologic
      roles of mitochondrial fusion and fission in highly differentiated cells using
      tissue-specific knockout mice remains a challenge for the future.

PMID- 22871171
TI  - Specific labeling of zinc finger proteins using noncanonical amino acids and
      copper-free click chemistry.
AB  - Zinc finger proteins (ZFPs) play a key role in transcriptional regulation and
      serve as invaluable tools for gene modification and genetic engineering.
      Development of efficient strategies for labeling metalloproteins such as ZFPs is
      essential for understanding and controlling biological processes. In this work,
      we engineered ZFPs containing cysteine-histidine (Cys2-His2) motifs by metabolic
      incorporation of the unnatural amino acid azidohomoalanine (AHA), followed by
      specific protein labeling via click chemistry. We show that cyclooctyne promoted
      [3 + 2] dipolar cycloaddition with azides, known as copper-free click chemistry,
      provides rapid and specific labeling of ZFPs at high yields as determined by mass
      spectrometry analysis. We observe that the DNA-binding activity of ZFPs labeled
      by conventional copper-mediated click chemistry was completely abolished, whereas
      ZFPs labeled by copper-free click chemistry retain their sequence-specific DNA
      binding activity under native conditions, as determined by electrophoretic
      mobility shift assays, protein microarrays, and kinetic binding assays based on
      Forster resonance energy transfer (FRET). Our work provides a general framework
      to label metalloproteins such as ZFPs by metabolic incorporation of unnatural
      amino acids followed by copper-free click chemistry.

PMID- 22871172
TI  - Heteroleptic dipyrrinato complexes containing 5-ferrocenyldipyrromethene and
      dithiocarbamates as coligands: selective chromogenic and redox probes.
AB  - Six heteroleptic dipyrrinato complexes [Ni(fcdpm)(dedtc)] (1),
      [Ni(fcdpm)(dipdtc)] (2), [Ni(fcdpm)(dbdtc)] (3), [Pd(fcdpm)(dedtc)] (4),
      [Pd(fcdpm)(dipdtc)] (5), and [Pd(fcdpm)(dbdtc)] (6) (fcdpm = 5
      ferrocenyldipyrromethene; dedtc = diethyldithiocarbamate; dipdtc =
      diisopropyldithiocarbamate; dbdtc = dibutyldithiocarbamate) have been synthesized
      and characterized by elemental analyses and spectral (ESI-MS, IR, (1)H, (13)C
      NMR, UV-vis) and electrochemical studies. Crystal structures of 1, 2, 4, and 5
      have been authenticated by X-ray single-crystal analyses. Nickel-based complexes
      1-3 display selective chromogenic and redox sensing for Hg(2+) and Pb(2+) ions,
      while palladium complexes 4-6 display selective chromogenic and redox sensing
      only for Hg(2+). Electronic absorption, ESI-MS, and electrochemical studies
      indicated that sensing arises from interaction between 1-3 and Hg(2+)/Pb(2+)
      through sulfur of the coordinated dithiocarbamates, while it arises from the
      pyrrolic nitrogen of fcdpm and dithiocarbamate sulfur from 4-6 and Hg(2+).
      Different modes of binding between Ni and Pd complexes have further been
      supported by theoretical studies. The receptor-cation binding constants (K(a))
      and stoichiometry between probes and Hg(2+)/Pb(2+) have been estimated by the
      Benesi-Hildebrand method and Job's plot analysis. Detection limits for 1-3 toward
      Hg(2+)/Pb(2+) and 4-6 for Hg(2+) have been found to be reasonably high.

PMID- 22871173
TI  - Weight loss among female health care workers--a 1-year workplace based randomized
      controlled trial in the FINALE-health study.
AB  - BACKGROUND: Weight management constitutes a substantial problem particularly
      among groups of low socio-economic status. Interventions at work places may be a
      solution, but high quality worksite interventions documenting prolonged weight
      loss are lacking. This paper presents results of an intervention aimed to achieve
      a 12 months weight loss among overweight health care workers. METHODS: Ninety
      eight overweight female health care workers were randomized into an intervention
      or a reference group. The intervention consisted of diet, physical exercise and
      cognitive behavioral training during working hours 1 hour/week. The reference
      group was offered monthly oral presentations. Several anthropometric measures,
      blood pressure, cardiorespiratory fitness, maximal muscle strength, and
      musculoskeletal pain were measured before and after the 12-months intervention
      period. Data were analyzed by intention-to-treat analysis. RESULTS: The
      intervention group significantly reduced body weight by 6 kg (p < 0.001), BMI by
      2.2 (p < 0.001) and body fat percentage by 2.8 (p < 0.001). There were no
      statistical reductions in the control group, resulting in significant differences
      between the two groups over time. CONCLUSIONS: The intervention generated
      substantial reductions in body weight, BMI and body fat percentage among
      overweight female health care workers over 12 months. The positive results
      support the workplace as an efficient arena for weight loss among overweight
      females. TRIAL REGISTRATION: NCT01015716.

PMID- 22871175
TI  - Emergency department diagnosis of upper extremity deep venous thrombosis using
      bedside ultrasonography.
AB  - A 27-year-old man presents to the emergency department with a 1-day history of
      severe right upper extremity pain and swelling. The patient's status is post open
      reduction internal fixation for a left tibial plateau fracture, which was
      complicated by methicillin-sensitive Staphylococcus aureus osteomyelitis. A
      peripherally inserted central catheter (PICC) line was subsequently placed for
      intravenous antibiotic therapy. Emergency department bedside ultrasound
      examination of both the right axillary vein and subclavian vein near the PICC
      line tip revealed deep venous thrombosis of both veins. Bedside upper extremity
      vascular ultrasonography can assist in the rapid diagnosis of upper extremity
      deep venous thrombosis in the emergency department.

PMID- 22871174
TI  - CrMPK3, a mitogen activated protein kinase from Catharanthus roseus and its
      possible role in stress induced biosynthesis of monoterpenoid indole alkaloids.
AB  - BACKGROUND: Mitogen activated protein kinase (MAPK) cascade is an important
      signaling cascade that operates in stress signal transduction in plants. The
      biologically active monoterpenoid indole alkaloids (MIA) produced in Catharanthus
      roseus are known to be induced under several abiotic stress conditions such as
      wounding, UV-B etc. However involvement of any signaling component in the
      accumulation of MIAs remains poorly investigated so far. Here we report isolation
      of a novel abiotic stress inducible Catharanthus roseus MAPK, CrMPK3 that may
      have role in accumulation of MIAs in response to abiotic stress. RESULTS: CrMPK3
      expressed in bacterial system is an active kinase as it showed auto
      phosphorylation and phosphorylation of Myelin Basic Protein. CrMPK3 though
      localized in cytoplasm, moves to nucleus upon wounding. Wounding, UV treatment
      and MeJA application on C. roseus leaves resulted in the transcript accumulation
      of CrMPK3 as well as activation of MAPK in C. roseus leaves. Immuno-precipitation
      followed by immunoblot analysis revealed that wounding, UV treatment and methyl
      jasmonate (MeJA) activate CrMPK3. Transient over-expression of CrMPK3 in C.
      roseus leaf tissue showed enhanced expression of key MIA biosynthesis pathway
      genes and also accumulation of specific MIAs. CONCLUSION: Results from our study
      suggest a possible involvement of CrMPK3 in abiotic stress signal transduction
      towards regulation of transcripts of key MIA biosynthetic pathway genes,
      regulators and accumulation of major MIAs.

PMID- 22871176
TI  - The role of oxidative stress in diazinon-induced tissues toxicity in Wistar and
      Norway rats.
AB  - Diazinon (DZN) is an organophosphate pesticide widely used in agricultural to
      control insects and in veterinary medicine to control ectoparasites. This study
      investigated the induction of oxidative stress in the brain, heart, and spleen of
      Wistar and Norway rats treated with acute doses of DZN. Female Wistar and Norway
      rats were treated with 25, 50, 100, and 200 mg/kg of DZN by intraperitoneal
      injection. The animals were sacrificed 24 h after treatment, and tissues were
      isolated and analyzed. The result of this study shows that DZN at higher doses
      increased the level of malondialdehyde, superoxide dismutase and glutathione S
      transferase activities and decreased glutathione (GSH) level, lactate
      dehydrogenase, and cholinesterase activities in the brain, heart, and spleen of
      both rat strains. At these concentrations, DZN toxicity also lead to a
      significant decrease in catalase (CAT) activity in all tissues of Wistar rat and
      brain of Norway rat, while it increased heart CAT activity in Norway rat.
      However, the alteration of these parameters was observed at lower doses of DZN in
      Wistar rat. These results suggest that DZN at higher doses induces the production
      of free radicals and oxidative stress in rat tissues and strains by alteration of
      antioxidant enzyme activity, depletion of GSH, and increasing lipid peroxidation.
      Induction of oxidative stress in DZN-treated rats is in the order of brain >
      heart > spleen. Wistar rats appear to be more sensitive to the effects of DZN on
      oxidative stress induction compared to Norway rat.

PMID- 22871179
TI  - Effects of a multidisciplinary group rehabilitation programme on participation of
      the visually impaired elderly: a pilot study.
AB  - PURPOSE: To pilot test the newly developed multidisciplinary group rehabilitation
      programme Visually Impaired elderly Persons Participating (VIPP). METHOD: A
      single group pretest-posttest design pilot study included 29 visually impaired
      persons (>= 55 years). The intervention (20 weekly meetings) consisted of four
      components (practical training; education, social interaction, counselling and
      training of problem-solving skills; individual and group goal setting; home-based
      exercise programme). Participation was assessed with the Utrecht Scale for
      Evaluation of Rehabilitation-Participation (USER-P) and the Impact on
      Participation and Autonomy (IPA) questionnaire at baseline, immediately and 6
      months after the intervention. RESULTS: At scale level, no statistical
      significant changes over time were found whereas the effect size indicated small
      effects for restrictions and satisfaction with participation, and a medium effect
      for autonomy outdoors. At item level, improvements tended to occur in frequency
      of housekeeping, in restrictions in housekeeping and outdoor activities and in
      satisfaction with the partner relationship. Satisfaction with leisure indoors and
      autonomy regarding using leisure time tended to increase as well. CONCLUSIONS:
      The tentative conclusion of this small-scale pilot study is that the VIPP
      programme modestly benefits perceived restrictions in participation, satisfaction
      with participation and autonomy outdoors of the visually impaired elderly. These
      preliminary findings warrant further investigation.

PMID- 22871178
TI  - The Cell Collective: toward an open and collaborative approach to systems
      biology.
AB  - BACKGROUND: Despite decades of new discoveries in biomedical research, the
      overwhelming complexity of cells has been a significant barrier to a fundamental
      understanding of how cells work as a whole. As such, the holistic study of
      biochemical pathways requires computer modeling. Due to the complexity of cells,
      it is not feasible for one person or group to model the cell in its entirety.
      RESULTS: The Cell Collective is a platform that allows the world-wide scientific
      community to create these models collectively. Its interface enables users to
      build and use models without specifying any mathematical equations or computer
      code - addressing one of the major hurdles with computational research. In
      addition, this platform allows scientists to simulate and analyze the models in
      real-time on the web, including the ability to simulate loss/gain of function and
      test what-if scenarios in real time. CONCLUSIONS: The Cell Collective is a web
      based platform that enables laboratory scientists from across the globe to
      collaboratively build large-scale models of various biological processes, and
      simulate/analyze them in real time. In this manuscript, we show examples of its
      application to a large-scale model of signal transduction.

PMID- 22871181
TI  - Computational modelling and analysis of mechanical conditions on cell locomotion
      and cell-cell interaction.
AB  - Between other parameters, cell migration is partially guided by the mechanical
      properties of its substrate. Although many experimental works have been developed
      to understand the effect of substrate mechanical properties on cell migration,
      accurate 3D cell locomotion models have not been presented yet. In this paper, we
      present a novel 3D model for cells migration. In the presented model, we assume
      that a cell follows two main processes: in the first process, it senses its
      interface with the substrate to determine the migration direction and in the
      second process, it exerts subsequent forces to move. In the presented model, cell
      traction forces are considered to depend on cell internal deformation during the
      sensing step. A random protrusion force is also considered which may change cell
      migration direction and/or speed. The presented model was applied for many cases
      of migration of the cells. The obtained results show high agreement with the
      available experimental and numerical data. 

PMID- 22871182
TI  - Classification and regression tree (CART) model to predict pulmonary tuberculosis
      in hospitalized patients.
AB  - BACKGROUND: Tuberculosis (TB) remains a public health issue worldwide. The lack
      of specific clinical symptoms to diagnose TB makes the correct decision to admit
      patients to respiratory isolation a difficult task for the clinician. Isolation
      of patients without the disease is common and increases health costs. Decision
      models for the diagnosis of TB in patients attending hospitals can increase the
      quality of care and decrease costs, without the risk of hospital transmission. We
      present a predictive model for predicting pulmonary TB in hospitalized patients
      in a high prevalence area in order to contribute to a more rational use of
      isolation rooms without increasing the risk of transmission. METHODS: Cross
      sectional study of patients admitted to CFFH from March 2003 to December 2004. A
      classification and regression tree (CART) model was generated and validated. The
      area under the ROC curve (AUC), sensitivity, specificity, positive and negative
      predictive values were used to evaluate the performance of model. Validation of
      the model was performed with a different sample of patients admitted to the same
      hospital from January to December 2005. RESULTS: We studied 290 patients admitted
      with clinical suspicion of TB. Diagnosis was confirmed in 26.5% of them.
      Pulmonary TB was present in 83.7% of the patients with TB (62.3% with positive
      sputum smear) and HIV/AIDS was present in 56.9% of patients. The validated CART
      model showed sensitivity, specificity, positive predictive value and negative
      predictive value of 60.00%, 76.16%, 33.33%, and 90.55%, respectively. The AUC was
      79.70%. CONCLUSIONS: The CART model developed for these hospitalized patients
      with clinical suspicion of TB had fair to good predictive performance for
      pulmonary TB. The most important variable for prediction of TB diagnosis was
      chest radiograph results. Prospective validation is still necessary, but our
      model offer an alternative for decision making in whether to isolate patients
      with clinical suspicion of TB in tertiary health facilities in countries with
      limited resources.

PMID- 22871183
TI  - Craniosynostosis with ectopia lentis and a homozygous 20-base deletion in
      ADAMTSL4.
AB  - Craniosynostosis with ectopia lentis has been described five times since 1950
      with unknown inheritance and variable phenotype. The patient was diagnosed with
      right coronal synostosis at age 10 weeks requiring surgery, and bilateral ectopia
      lentis with high myopia at 10 months. No other family member was affected. There
      is no known consanguinity within the family. Genetic screening ruled out FBN1,
      TGFBR2, and the known craniosynostosis hotspots (FGFR2 exon 8 and exon 10 and
      FGFR3 exon 6) as the cause. A homozygous deletion in exon 6 of ADAMTSL4
      (c.767_786del 20) that has been shown to cause isolated ectopia lentis was found.
      The mutation results in a premature termination codon (p.Gln256ProfsX38). The
      proband's mother, father and one sibling are heterozygous carriers of the
      mutation. This is the first detailed report of a possible genetic determinant of
      craniosynostosis with ectopia lentis. Although this mutation causes isolated
      ectopia lentis, this may be evidence of pleiotropic effects of ADAMTSL4 and may
      represent an overlapping syndrome with a causative mutation in ADAMTSL4. These
      findings need to be confirmed in further cases with craniosynostosis and ectopia
      lentis.

PMID- 22871185
TI  - Water-dependent micromechanical and rheological properties of silica colloidal
      crystals studied by nanoindentation.
AB  - Here we show the suitability of nanoindentation to study in detail the
      micromechanical response of silica colloidal crystals (CCs). The sensitivity to
      displacements smaller than the submicrometer spheres size, even resolving
      discrete events and superficial features, revealed particulate features with
      analogies to atomic crystals. Significant robustness, long-range structural
      deformation, and large energy dissipation were found. Easily implemented
      temperature/rate-dependent nanoindentation quantified the paramount role of
      adsorbed water endowing silica CCs with properties of wet granular materials like
      viscoplasticity. A novel "nongranular" CC was fabricated by substituting
      capillary bridges with silica necks to directly test water-independent mechanical
      response. Silica CCs, as specific (nanometric, ordered) wet granular assemblies
      with well-defined configuration, may be useful model systems for granular science
      and capillary cohesion at the nanoscale.

PMID- 22871184
TI  - Abnormality in the external limiting membrane in early Stargardt disease.
AB  - Stargardt disease (STGD1) is caused by mutations in the ABCA4 gene. It has
      previously been reported that abnormalities in STGD1 may be detectable in the
      photoreceptors using spectral domain-optical coherence tomography (SD-OCT) prior
      to the detection of retinal pigment epithelium abnormalities. We present a 5-year
      old asymptomatic girl with normal appearing fundi who possessed pathogenic ABCA4
      variants on both chromosomes and where thickening of the external limiting
      membrane was the only abnormality detected on SD-OCT.

PMID- 22871186
TI  - Everything is better in 3D: why transcatheter aortic valve replacement should be
      guided by multidetector computed tomography.

PMID- 22871187
TI  - Blood pressure, fluid retention and the cardiovascular risk of drugs.

PMID- 22871189
TI  - Methicillin-resistant Staphylococcus aureus and infective endocarditis: more than
      a nuisance in the face of resistance.

PMID- 22871190
TI  - Atopaxar: a review of its mechanism of action and role in patients with coronary
      artery disease.
AB  - Platelet activation and aggregation is a complex and key process in thrombus
      formation after the rupture of an atherosclerotic plaque, which can lead to an
      acute coronary syndrome. Aspirin, an irreversible inhibitor of thromboxane A(2)
      synthesis, in combination with an inhibitor of P2Y(12) ADP platelet receptors
      (clopidogrel, prasugrel or ticagrelor), represents the current standard of care
      of antiplatelet therapy for patients with acute coronary syndrome and in those
      patients undergoing percutaneous coronary intervention. Despite the benefit of
      these agents, the risk of thrombotic events and bleeding complications may still
      occur while on such antiplatelet treatment regimens, thus representing an
      important limitation. Thrombin is one of the most important platelet activators.
      The inhibition of thrombin-mediated platelet activation by means of protease
      activated receptor-1 inhibitors represents an attractive therapeutic option for
      patients with atherothrombotic disease processes. This article provides an
      overview on atopaxar (E5555), an orally active protease-activated receptor-1
      antagonist that has recently completed Phase II clinical investigation.

PMID- 22871191
TI  - An update on the clinical development of dalcetrapib (RO4607381), a cholesteryl
      ester transfer protein modulator that increases HDL cholesterol levels.
AB  - CETP is the target of CETP inhibitors such as anacetrapib and the modulator
      dalcetrapib. Both molecules have entered Phase III clinical trials, with the
      ultimate goal of reducing cardiovascular events by raising HDL cholesterol. At
      the 600-mg dose selected for the dal-OUTCOMES study, dalcetrapib is expected to
      inhibit CETP activity by approximately 30% and raise HDL-C by approximately 30%
      with limited effects on LDL cholesterol. Importantly, dalcetrapib does not raise
      blood pressure or aldosterone levels, two effects previously associated with the
      CETP inhibitor torcetrapib. Dalcetrapib has been well tolerated at the 600-mg
      dose. In the dal-PLAQUE atherosclerosis imaging study, dalcetrapib reduced the
      enlargement of total vessel area over time. In May 2012, following the results of
      the second interim analysis of dal-OUTCOMES, the Data and Safety Monitoring Board
      recommended stopping the study owing to a lack of clinically significant benefit,
      which was followed by Roche's (Basel, Switzerland) decision to terminate the
      study and the dalcetrapib program (dal-HEART). Contrary to anacetrapib, a potent
      CETP inhibitor that markedly increases HDL cholesterol and significantly reduces
      LDL cholesterol, dalcetrapib has allowed us to test the hypothesis that an
      isolated, moderate elevation in HDL cholesterol prevents cardiovascular events.

PMID- 22871192
TI  - Rivaroxaban for stroke prevention in atrial fibrillation and secondary prevention
      in patients with a recent acute coronary syndrome.
AB  - The occurrence of disabling stroke, the major fatal consequence of atrial
      fibrillation, can be reduced by almost two-thirds with warfarin oral
      anticoagulation. Recent estimates on the prevalence of atrial fibrillation in the
      USA suggest that approximately 3 million people suffer from this common cardiac
      arrhythmia, therefore, the socioeconomic impact of adequate oral anticoagulation
      is enormous. Rivaroxaban, a direct orally available factor Xa inhibitor, is the
      first of a new class of drugs that target a central factor of the coagulation
      cascade upstream of thrombin. In the ROCKET AF clinical trial, rivaroxaban
      demonstrated noninferiority compared with warfarin for stroke prevention in
      patients with atrial fibrillation, while intracranial and fatal bleeding occurred
      less frequently with rivaroxaban treatment. Rivaroxban has recently been approved
      for the prevention of stroke and systemic embolism in patients with nonvalvular
      atrial fibrillation by the US FDA and EMA. Very recently, rivaroxaban in addition
      to dual antiplatelet therapy, was shown to reduce mortality in patients with a
      recent acute coronary syndrome in the ATLAS ACS 2-TIMI 51 clinical trial. The
      clinical evaluation of rivaroxaban in cardiovascular disease and the results of
      the ROCKET AF study, the landmark clinical trial of rivaroxaban for stroke
      prevention, are discussed along with the unique pharmacological profile of
      rivaroxaban.

PMID- 22871193
TI  - Is transfemoral aortic valve implantation possible without contrast medium in
      patients with renal and multiorgan failure?
AB  - Transfemoral aortic valve implantation has recently emerged as a therapeutic
      option for patients with symptomatic, severe aortic stenosis for whom standard
      surgical aortic valve surgery is not suitable. Aortic valvuloplasty and valve
      positioning is normally performed under fluoroscopy and requires several
      injections of contrast medium. In critically ill patients with advanced renal
      insufficiency, contrast media administration can further increase renal damage;
      therefore, an echocardiogram and fluoroscopy-guided procedure, using the
      calcified contours of the stenotic aortic valve as a landmark may be a useful
      alternative. We report the first successful transfemoral aortic valve
      implantation procedure performed under fluoroscopy and transesophageal
      echocardiogram control, without administration of contrast medium injections in a
      patient with severe renal insufficiency and multiorgan failure.

PMID- 22871194
TI  - Indications for daptomycin use in endocarditis and pacemaker lead infection and
      outcomes in Leeds, UK.
AB  - Infective endocarditis now comprises an increasingly complex mixture of
      endocardial infections, with staphylococci as the predominant cause. Although
      vancomycin has been an important therapeutic option for several decades, reduced
      susceptibility is emerging. Daptomycin is a relatively new antimicrobial agent,
      approved for right-sided endocarditis, but the data for other forms of
      endocarditis are limited. Here we report clinical data from the Leeds
      Endocarditis Service (Leeds, UK) for 19 patients treated with daptomycin between
      January 2007 and December 2009. The majority of cases were caused by
      staphylococci. All patients were treated with 6 mg/kg with a median treatment
      duration of 29 days. In total, 53% of patients were cured with antimicrobial
      regimens, which included daptomycin. Four patients (21%) died during therapy or
      within 30 days of stopping treatment. The current series is representative of
      everyday clinical practice and reflects the current difficulties in managing
      endocarditis.

PMID- 22871195
TI  - Aspirin sensitivity and coronary artery disease: implications for the practicing
      cardiologist.
AB  - Aspirin is the most commonly used antiplatelet agent in patients with coronary
      artery disease (CAD). It continues to play a key role as an antiplatelet agent
      given its long-term safety, efficacy and low cost. Aspirin or NSAID
      hypersensitivity is not an uncommon occurrence and can vary from generalized
      urticaria and angioedema to exacerbation of upper and lower respiratory tract
      reactions. It is not uncommon for clinicians to avoid using aspirin and
      alternative agents when encountering aspirin hypersensitivity among CAD patients.
      However, given the critical role of aspirin in CAD patients, particularly among
      those who receive the drug-eluting stents, aspirin desensitization can be useful.
      This article highlights the importance of aspirin desensitization, the mechanism
      and the process involved. We draw attention to recently described rapid
      desensitization protocols and how they can be more useful than the old procedure.

PMID- 22871197
TI  - From particles to patients: oxidative stress and the cardiovascular effects of
      air pollution.
AB  - Air pollution, especially airborne particulate matter (PM), is associated with an
      increase in both morbidity and mortality from cardiovascular disease, although
      the underlying mechanisms remain incompletely established. The one consistent
      observation that links the pulmonary and cardiovascular effects of inhaled PM is
      oxidative stress. This article examines the evidence for the role of oxidative
      stress in the cardiovascular effects of air pollution, beginning with
      observations from epidemiological and controlled exposure studies and then
      exploring potential mechanistic pathways involving free radical generation from
      PM itself, to effects of PM on cell cultures, isolated organs, healthy animals
      and animal models of disease. Particular emphasis is placed on the vascular and
      atherosclerotic effects of urban air pollution and diesel exhaust emissions as
      rich sources of environmental ultrafine particles.

PMID- 22871196
TI  - The future of warfarin pharmacogenetics in under-represented minority groups.
AB  - Genotype-based dosing recommendations are provided in the US FDA-approved
      warfarin labeling. However, data that informed these recommendations were from
      predominately Caucasian populations. Studies show that variants contributing to
      warfarin dose requirements in Caucasians provide similar contributions to dose
      requirements in US Hispanics, but significantly lesser contributions in African
      Americans. Further data demonstrate that variants occurring commonly in
      individuals of African ancestry, but rarely in other racial groups, significantly
      influence dose requirements in African-Americans. These data suggest that it is
      important to consider variants specific for African-Americans when implementing
      genotype-guided warfarin dosing in this population.

PMID- 22871198
TI  - Nuclear perfusion imaging for functional evaluation of patients with known or
      suspected coronary artery disease: the future is now.
AB  - Nuclear imaging, with both single-photon emission computed tomography and PET,
      has a well-established role in the assessment of patients with known or suspected
      coronary artery disease. There is a large body of evidence regarding the
      diagnostic accuracy and prognostic value of these modalities, however, they
      continue to evolve rapidly with advances in camera and tracer technology, as well
      as changes in imaging protocols to increase lab efficiency, improve image quality
      and to decrease radiation exposure to patients. Nuclear imaging also provides
      insights into atherogenesis at a molecular level and can be combined with other
      imaging modalities, providing both functional and structural data and
      complimentary information on the presence of coronary disease and its functional
      implications.

PMID- 22871199
TI  - Improving survival during heart transplantation: diagnosis of antibody-mediated
      rejection and techniques for the prevention of graft injury.
AB  - The diagnosis of antibody-mediated rejection (AMR) has presented a challenge due
      to the pleiomorphic immunologic responses that represent the condition. A
      consensus with regard to its pathological diagnosis continues to evolve. Due to
      an increasing number of sensitized patients undergoing heart transplantation, its
      incidence appears to be on the rise and the condition is associated with worse
      outcomes than acute cellular rejection. Treatment of AMR is also more difficult
      and response to increases in conventional immunosuppression is often limited.
      Risk factors for AMR include the use of ventricular assist devices, prior
      exposure to blood products, allografts and multiparity. Detection of
      alloantibodies with a high specificity and sensitivity allows risk stratification
      of recipients at potential risk of AMR. Desensitization and AMR treatment
      strategies are focused on several therapeutic targets, including suppression of T
      and B cells and elimination or inhibition of circulating antibodies.

PMID- 22871200
TI  - The significance of postprocedural aortic regurgitation after transcatheter
      aortic valve implantation on postprocedural prognosis.
AB  - Transcatheter aortic valve implantation (TAVI) is becoming a more and more
      important treatment for aortic valve stenosis in high-risk surgical patients.
      Furthermore, there currently is a discussion for the expansion of TAVI to
      intermediate-risk patients. In the past, surgical aortic valve replacement was
      the standard treatment, with excellent results in hemodynamic, as well as
      echocardiographic parameters and survival rates. However, the results of the
      Partner A and Partner B trials, as well as the ADVANCE study demonstrate the
      promise of establishing TAVI as a real alternative treatment option for aortic
      valve stenosis. One of the risks of a TAVI procedure is the occurrence of aortic
      regurgitation (AR) post-TAVI. Mild AR is a common finding after TAVI and seems
      not to be a clinical problem; however, occurrence of significant postprocedural
      AR after TAVI is still a problem. There is a clear association between
      significant postprocedural AR and clinical outcomes. Therefore, this review
      focuses on the occurrence, reasons, diagnostics, clinical impact and treatment
      options of AR post-TAVI.

PMID- 22871203
TI  - Syntheses, structures, and steady state and time resolved photophysical
      properties of a tetraiminodiphenol macrocyclic ligand and its dinuclear
      zinc(II)/cadmium(II) complexes with coordinating and noncoordinating anions.
AB  - The work in the present investigation reports the syntheses, structures, steady
      state, and time-resolved photophysical properties of a tetraiminodiphenol
      macrocyclic ligand H(2)L and its eight dinuclear zinc(II) complexes and one
      cadmium(II) complex having composition [Zn(2)L(H(2)O)(2)](ClO(4))(2).2CH(3)CN
      (1), [Zn(2)L(H(2)O)(2)](ClO(4))(2).2dmf (2), [Zn(2)L(H(2)O)(2)](NO(3))(2).2dmf
      (3), [Zn(2)LCl(2)] (4), [Zn(2)L(N(3))(2)] (5), [Zn(2)L(NCS)(2)] (6),
      [Zn(2)L(NCO)(2)] (7), [Zn(2)L(NCSe)(2)](2).dmf (8), and [Cd(2)L(OAc)(2)] (9) with
      various coordinating and noncoordinating anions. The structures of all the
      complexes 1-9 have been determined by single-crystal X-ray diffraction. The
      noncovalent interactions in the complexes result in the generation of the
      following topologies: two-dimensional network in 1, 2, 4, 6, 7, 8, and 9; three
      dimensional network in 5. Spectrophotometric and spectrofluorometric titrations
      of the diprotonated salt [H(4)L](ClO(4))(2) with triethylamine as well as with
      zinc(II) acetate and cadmium(II) acetate have been carried out, revealing
      fluorescence enhancement of the macrocyclic system by the base and the metal
      ions. Steady state fluorescence properties of [H(4)L](ClO(4))(2) and 1-9 have
      been studied and their quantum yields have been determined. Time resolved
      fluorescence behavior of [H(4)L](ClO(4))(2) and the dizinc(II) and dicadmium(II)
      complexes 1-9 have also been studied, and their lifetimes and radiative and
      nonradiative rate constants have been determined. The induced fluorescence
      enhancement of the macrocycle by zinc(II) and cadmium(II) is in line with the
      greater rate of increase of the radiative rate constants in comparison to the
      smaller rate of increase of nonradiative rate constants for the metal complexes.
      The fluorescence decay profiles of all the systems, being investigated here, that
      is, [H(4)L](ClO(4))(2) and 1-9, follow triexponential patterns, revealing that at
      least three conformers/components are responsible to exhibit the fluorescence
      decay behavior. The systems and studies in this report have been compared with
      those in the reports of the previously published similar systems, revealing some
      interesting aspects.

PMID- 22871204
TI  - Randomized comparison of the i-gelTM, the LMA SupremeTM, and the Laryngeal Tube
      Suction-D using clinical and fibreoptic assessments in elective patients.
AB  - BACKGROUND: The i-gelTM, LMA-Supreme (LMA-S) and Laryngeal Tube Suction-D (LTS-D)
      are single-use supraglottic airway devices with an inbuilt drainage channel. We
      compared them with regard to their position in situ as well as to clinical
      performance data during elective surgery. METHODS: Prospective, randomized,
      comparative study of three groups of 40 elective surgical patients each. Speed of
      insertion and success rates, leak pressures (LP) at different cuff pressures,
      dynamic airway compliance, and signs of postoperative airway morbidity were
      recorded. Fibreoptic evaluation was used to determine the devices' position in
      situ. RESULTS: Leak pressures were similar (i-gelTM 25.9, LMA-S 27.1, LTS-D 24.0
      cmH2O; the latter two at 60 cmH2O cuff pressure) as were insertion times (i-gelTM
      10, LMA-S 11, LTS-D 14 sec). LP of the LMA-S was higher than that of the LTS-D at
      lower cuff pressures (p <0.05). Insertion success rates differed significantly: i
      gelTM 95%, LMA-S 95%, LTS-D 70% (p <0.05). The fibreoptically assessed position
      was more frequently suboptimal with the LTS-D but this was not associated with
      impaired ventilation. Dynamic airway compliance was highest with the i-gelTM and
      lowest with the LTS-D (p <0.05). Airway morbidity was more pronounced with the
      LTS-D (p <0.01). CONCLUSION: All devices were suitable for ventilating the
      patients' lungs during elective surgery. TRIAL REGISTRATION: German Clinical
      Trial Register DRKS00000760.

PMID- 22871206
TI  - Titanium-oxo-clusters with dicarboxylates: single-crystal structure and
      photochromic effect.
AB  - Two titanium-oxo-clusters Ti(6)O(4)(o-BDC)(2)(o-BDC(i)Pr)(2)(O(i)Pr)(10) (1) and
      Ti(6)O(3)(o-BDC)(2)(O(i)Pr)(14) (2) (BDC = benzene dicarboxylate) were prepared
      by one-step in situ solvothermal synthesis. The compounds are the rare examples
      of the dicarboxylate-substituted titanium-oxo-clusters. Their crystal structures
      are successfully measured by single-crystal X-ray analysis. The Ti(6) oxo
      clusters of 1 and 2 are constructed by two dual corner-missing cube subunit,
      Ti(3)O(3). The two subunits are linked by double MU(3)-O bridges for 1 and single
      MU(2)-O bridge for 2, respectively, and the latter is a new type of carboxylate
      substituted titanium-oxo-cluster. A photochromic effect was observed upon
      irradiation of the crystals in the presence of alcohol. The light irradiation
      changed the color of the crystals from transparent to purple-gray. The Ti(III)
      signal was detected after the irradiation, and when the sample was exposured in
      air, superoxide diatomic O(2)(*-) radical was found. Photodegradation of the
      methyl orange in aqueous dispersions of microcrystals of the cluster 2 was
      carried out under UV cut white light with the assistance of H(2)O(2).

PMID- 22871201
TI  - Cardiotoxicity in childhood cancer survivors: strategies for prevention and
      management.
AB  - Advances in cancer treatment have greatly improved survival rates of children
      with cancer. However, these same chemotherapeutic or radiologic treatments may
      result in long-term health consequences. Anthracyclines, chemotherapeutic drugs
      commonly used to treat children with cancer, are known to be cardiotoxic, but the
      mechanism by which they induce cardiac damage is still not fully understood. A
      higher cumulative anthracycline dose and a younger age of diagnosis are only a
      few of the many risk factors that identify the children at increased risk of
      developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting
      from treatment initiation and well into adulthood, identifying the best
      cardioprotective measures to minimize the long-term damage caused by
      anthracyclines in children is imperative. Dexrazoxane is the only known agent to
      date, that is associated with less cardiac dysfunction, without reducing the
      oncologic efficacy of the anthracycline doxorubicin in children. Given the
      serious long-term health consequences of cancer treatments on survivors of
      childhood cancers, it is essential to investigate new approaches to improving the
      safety of cancer treatments.

PMID- 22871205
TI  - Routes to short-term memory indexing: lessons from deaf native users of American
      Sign Language.
AB  - Models of working memory (WM) have been instrumental in understanding
      foundational cognitive processes and sources of individual differences. However,
      current models cannot conclusively explain the consistent group differences
      between deaf signers and hearing speakers on a number of short-term memory (STM)
      tasks. Here we take the perspective that these results are not due to a temporal
      order-processing deficit in deaf individuals, but rather reflect different biases
      in how different types of memory cues are used to do a given task. We further
      argue that the main driving force behind the shifts in relative biasing is a
      consequence of language modality (sign vs. speech) and the processing they
      afford, and not deafness, per se.

PMID- 22871208
TI  - Cause-specific neonatal mortality in a neonatal care unit in Northern Tanzania: a
      registry based cohort study.
AB  - BACKGROUND: The current decline in under-five mortality shows an increase in
      share of neonatal deaths. In order to address neonatal mortality and possibly
      identify areas of prevention and intervention, we studied causes of admission and
      cause-specific neonatal mortality in a neonatal care unit at Kilimanjaro
      Christian Medical Centre (KCMC) in Tanzania. METHODS: A total of 5033 inborn
      neonates admitted to a neonatal care unit (NCU) from 2000 to 2010 registered at
      the KCMC Medical Birth Registry and neonatal registry were studied. Clinical
      diagnosis, gestational age, birth weight, Apgar score and date at admission and
      discharge were registered. Cause-specific of neonatal deaths were classified by
      modified Wigglesworth classification. Statistical analysis was performed in SPSS
      18.0. RESULTS: Leading causes of admission were birth asphyxia (26.8%),
      prematurity (18.4%), risk of infection (16.9%), neonatal infection (15.4%), and
      birth weight above 4000 g (10.7%). Overall mortality was 10.7% (536 deaths).
      Leading single causes of death were birth asphyxia (n = 245, 45.7%), prematurity
      (n = 188, 35.1%), congenital malformations (n = 49, 9.1%), and infections (n =
      46, 8.6%). Babies with birth weight below 2500 g constituted 29% of all
      admissions and 52.1% of all deaths. Except for congenital malformations, case
      fatality declined with increasing birth weight. Birth asphyxia was the most
      frequent cause of death in normal birth weight babies (n = 179/246, 73.1%) and
      prematurity in low birth weight babies (n = 178/188, 94.7%). The majority of
      deaths (n = 304, 56.7%) occurred within 24 hours, and 490 (91.4%) within the
      first week. CONCLUSIONS: Birth asphyxia in normal birth weight babies and
      prematurity in low birth weight babies each accounted for one third of all deaths
      in this population. The high number of deaths attributable to birth asphyxia in
      normal birth weight babies suggests further studies to identify causal
      mechanisms. Strategies directed towards making obstetric and newborn care timely
      available with proper antenatal, maternal and newborn care support with regular
      training on resuscitation skills would improve child survival.

PMID- 22871207
TI  - Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation,
      signaling, and therapeutics.
AB  - SIGNIFICANCE: Pulmonary arterial hypertension (PAH) is a disorder characterized
      by increased pulmonary vascular resistance and mean pulmonary artery pressure
      leading to impaired function of the right ventricle, reduced cardiac output, and
      death. An imbalance between vasoconstrictors and vasodilators plays an important
      role in the pathobiology of PAH. RECENT ADVANCES: Nitric oxide (NO) is a potent
      vasodilator in the lung, whose bioavailability and signaling pathway are impaired
      in PAH. It is now appreciated that the oxidative product of NO metabolism, the
      inorganic anion nitrite (NO(2)(-)), functions as an intravascular endocrine
      reservoir of NO bioactivity that can be reduced back to NO under physiological
      and pathological hypoxia. CRITICAL ISSUES: The conversion of nitrite to NO is
      controlled by coupled electron and proton transfer reactions between heme- and
      molybdenum-containing proteins, such as hemoglobin and xanthine oxidase, and by
      simple protonation and disproportionation, and possibly by catalyzed
      disproportionation. The two major sources of nitrite (and nitrate) are the
      endogenous L-arginine-NO pathway, by oxidation of NO, and the diet, with
      conversion of nitrate from diet into nitrite by oral commensal bacteria. In the
      current article, we review the enzymatic formation of nitrite and the available
      data regarding its use as a therapy for PAH and other cardiovascular diseases.
      FUTURE DIRECTIONS: The successful efficacy demonstrated in several animal models
      and safety in early clinical trials suggest that nitrite may represent a
      promising new therapy for PAH.

PMID- 22871209
TI  - Performance of children on the Community Balance and Mobility Scale.
AB  - This study describes the performance of children 8-11 years of age on the
      Community Balance and Mobility Scale (CB&M) and associations between performance
      and age, body mass index (BMI), and sex. A convenience sample of 84 was
      recruited. The CB&M was administered using instructions we developed for
      children. Mean CB&M total scores (95% confidence intervals) for age groups were
      8: 70.1 (64.2, 76.1); 9: 72.8 (68.7, 76.8); 10: 79.2 (76.6, 81.7); and 11: 82.9
      (79.2, 86.5). None of the children achieved the maximum score. Scores increased
      with age, and overweight/obese children had relatively lower scores. There were
      no significant differences between males and females. A regression analysis found
      28.1% of the variation in the CB&M total scores was explained by age (p < .001),
      BMI (p < .01), and sex (p = .25) suggesting that other factors contribute to
      variation in balance and mobility proficiency. The modified instructions and
      scoring patterns from this study can assist in using the CB&M in children of ages
      8-11 years.

PMID- 22871211
TI  - Reaerosolization of Bacillus spp. in outdoor environments: a review of the
      experimental literature.
AB  - Reaerosolization or resuspension-that is, the reintroduction of previously
      airborne particles into the atmosphere-is a complex phenomenon. Microbial
      reaerosolization is particularly poorly understood because few studies have been
      done in this area, and many of the studies that have been performed are not in
      the peer-reviewed literature. The reaerosolization of Bacillus anthracis in
      outdoor environments is of particular concern because of its stability and
      potential for use as a biological weapon. This review pulls together data from
      more than 30 publications, spanning field and laboratory experiments, to
      summarize the current state of our understanding of Bacillus spp.
      reaerosolization in outdoor environments.

PMID- 22871210
TI  - CD133(+)CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor
      prognosis of patients.
AB  - BACKGROUND: Colorectal cancer (CRC), which frequently metastasizes to the liver,
      is one of the three leading causes of cancer-related deaths worldwide. Growing
      evidence suggests that a subset of cells exists among cancer stem cells. This
      distinct subpopulation is thought to contribute to liver metastasis; however, it
      has not been fully explored in CRC yet. METHODS: Flow cytometry analysis was
      performed to detect distinct subsets with CD133 and CXCR4 markers in human
      primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of
      different subpopulations derived from the colon cancer cell line HCT116 were
      compared in vitro and in vivo. The roles of epithelial-mesenchymal transition
      (EMT) and stromal-cell derived factor-1 (SDF-1) in the metastatic process were
      also investigated. A survival curve was used to explore the correlation between
      the content of CD133(+)CXCR4(+) cancer cells and patient survival. RESULTS: In
      human specimens, the content of CD133(+)CXCR4(+) cells was higher in liver
      metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells
      were restricted to CD133(+) cells in the HCT116 cell line, with CXCR4 expression
      having no impact on the 'stemness' properties. We found that
      CD133(+)CXCR4(+)cancer cells had a high metastatic capacity in vitro and in vivo.
      Compared with CD133(+)CXCR4(-) cells, CD133(+)CXCR4(+)cancer cells experienced
      EMT, which contributed partly to their metastatic phenotype. We then determined
      that SDF-1/CXCL12 treatment could further induce EMT in CD133(+)CXCR4(+)cancer
      cells and enhance their invasive behavior, while this could not be observed in
      CD133(+)CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4
      antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene)]bis-1,4,8,11 
      tetraazacyclotetradecane octahydrochloride), inhibited metastatic tumor growth in
      a mouse hepatic metastasis model. Finally, a high percentage of
      CD133(+)CXCR4(+)cells in human primary CRC was associated with a reduced two-year
      survival rate. CONCLUSIONS: Strategies targeting the SDF-1/CXCR4 interaction may
      have important clinical applications in the suppression of colon cancer
      metastasis. Further investigations on how high expression of CXCR4 and EMT occur
      in this identified cancer stem cell subset are warranted to provide insights into
      our understanding of tumor biology.

PMID- 22871212
TI  - Inappropriately normal plasma ACTH and cortisol concentrations in the face of
      increased circulating interleukin-6 concentration in exercise in patients with
      sarcoidosis.
AB  - Sarcoidosis is an autoimmune disease, and hypothalamic-pituitary-adrenal (HPA)
      axis activity is blunted in autoimmunity. Exercise stimulates the HPA axis, and
      we hypothesized that in sarcoidosis patients responses to treadmill exercise
      would be reduced. Hence, we studied 44 sarcoidosis patients [27 untreated (age,
      mean +/- SD, 42 +/- 2 years, 12 males, 15 females) and 17 dexamethasone treated
      (age, 46 +/- 4 years, 7 males, 10 females)] and 20 healthy controls (40 +/- 5
      years old, 9 males, 11 females). Blood samples were drawn before, at peak
      (exhaustion), and 15 min after treadmill exercise for adrenocorticotropic hormone
      (ACTH), cortisol, tumor necrosis factor (TNF), interleukin-1beta (IL-1beta) and
      IL-6 measurements. At peak, plasma ACTH (pg/ml) was increased in untreated (mean
      +/- SE, DeltaACTH = 162.8 +/- 29.9) and treated (DeltaACTH = 123.3 +/- 48.1)
      patients and controls (DeltaACTH = 112.3 +/- 41.7). Post-exercise, cortisol
      (ng/ml) was increased (p < 0.05) in untreated patients (Deltacortisol = 48.4 +/-
      14.7) and controls (Deltacortisol = 46.0 +/- 15.9), but not significantly in
      treated patients (Deltacortisol = 1.43 +/- 2.56). At baseline, serum IL-6 (pg/ml)
      and TNF (pg/ml) were higher in untreated (3.02 +/- 0.54 and 3.89 +/- 0.72) and
      treated (1.75 +/- 0.33 and 2.16 +/- 1.00) patients, respectively, than in
      controls (0.80 +/- 0.66 and 1.58 +/- 0.32). At peak exercise, IL-6 was increased
      in untreated (DeltaIL-6 = 0.96 +/- 0.14) and treated (DeltaIL-6 = 0.91 +/- 0.47)
      patients and controls (DeltaIL-6 = 0.96 +/- 0.18); IL-1beta was increased only in
      controls. Hence, the HPA axis of untreated sarcoidosis patients and controls
      responded similarly to treadmill exercise. In sarcoidosis patients, increased IL
      6 was associated with HPA stimulation. Cortisol concentrations were similar
      between patients and controls, although IL-6 concentrations were higher in
      patients. Thus, in the face of chronically elevated IL-6 levels in sarcoidosis,
      there may be dysfunctional IL-6-induced HPA responses or HPA adaptation to high
      IL-6 concentrations.

PMID- 22871213
TI  - Femoral tunneled central venous catheters for terminally ill patients with
      cancer.
AB  - BACKGROUND: Oral administration of medication is often difficult in terminally
      ill patients with cancer. These patients require intravenous routes for high-dose
      opioid administration and/or parenteral nutrition. When the superior vena cava
      (SVC) is unsuitable for central vein catheter insertion (i.e., in patients with
      mediastinal masses involving the SVC), alternative access routes are needed. Of
      these, the femoral vein is most utilized. In our experience, the femoral tunneled
      catheter (FTC) is easy and safe to use. We retrospectively studied FTC outcomes
      in terminally ill patients with cancer. MATERIALS AND METHODS: Charts of
      consecutive patients admitted to the palliative care unit between April 2008 and
      December 2011 were reviewed. FTC is inserted into the vein by the single-puncture
      method using a 16-gauge catheter with a 14-gauge peel-away introducer. RESULTS:
      Eleven patients underwent FTC insertion. In total, there were 207 days of FTC
      placement; the mean period in place was 19+/-15 days. Eight patients received
      parenteral opioid therapy, high doses in four cases, via FTCs. Complications were
      incidental arterial puncture and poor infusion rate due to hip joint bending in
      one case each. Neither catheter-related infection nor clinical venous thrombosis
      occurred. CONCLUSIONS: FTCs were successfully inserted, with a low complication
      rate. FTC, a simple technique, might be an acceptable alternative in selected
      terminally ill patients with cancer, when SVC insertion is difficult or
      contraindicated.

PMID- 22871214
TI  - Case-control studies of sporadic enteric infections have limited usefulness in
      evaluating key foodborne disease risk factors.

PMID- 22871216
TI  - Comparison of computerized tomography and ultrasound for diagnosing soft tissue
      abscesses.
AB  - BACKGROUND: The diagnosis of a superficial abscess is usually obtained through
      history and physical exam but bedside ultrasound (US) and computerized tomography
      (CT) are sometimes used to assist in the diagnosis. It is unclear which imaging
      modality is superior for patients with superficial soft tissue infections. We
      compared the diagnostic accuracy of CT and US in patients with skin and soft
      tissue infections. METHODS: Patients presenting with a suspected skin abscess
      that underwent both US and CT imaging were eligible for inclusion. Two physicians
      blinded to patient characteristics and other imaging results prospectively
      reviewed the CT and US images for pre-defined image elements, and in
      circumstances where there was disagreement between these interpretations, a third
      physician adjudicated the findings. The presence or absence of an abscess cavity
      was noted on imaging. Imaging detail was summarized using a pre-specified 4-point
      scale based on the degree of visible detail with higher numbers corresponding to
      greater detail. The clinical presence of an abscess was defined by surgical
      evacuation of purulence. Sensitivity and specificity for both CT and US were
      calculated using Chi square analysis. Comparison between imaging detail was
      performed using a Student's T-test. Data are presented with (95% confidence
      intervals) unless otherwise noted. RESULTS: Over an 18 month period 612 patients
      received a soft tissue bedside ultrasound with 65 of those patients receiving a
      CT for the same complaint. 30 of these 65 patients had an abscess located in the
      head and neck (37%), buttock (17%), lower extremity (17%), upper extremity (13%),
      torso (13%), or hand (3%). US demonstrated a sensitivity and specificity for the
      diagnosis of abscess of 96.7% (87.0% to 99.4%) and 85.7% (77.4% to 88.0%)
      respectively. The overall sensitivity and specificity of CT for the diagnosis of
      an abscess was 76.7% (65.5% to 82.8%) and 91.4% (81.8% to 96.7%) respectively
      Overall image detail ratings were superior for US compared to CT (3.5 vs 2.3, p =
      0.0001). CONCLUSION: US is more sensitive then CT, but CT is more specific for
      superficial soft tissue abscesses. US demonstrated more visible detail within the
      abscess cavity compared to CT.

PMID- 22871215
TI  - Collagen type I and decorin expression in tenocytes depend on the cell isolation
      method.
AB  - BACKGROUND: The treatment of rotator cuff tears is still challenging. Tendon
      tissue engineering (TTE) might be an alternative in future. Tenocytes seem to be
      the most suitable cell type as they are easy to obtain and no differentiation in
      vitro is necessary. The aim of this study was to examine, if the long head of the
      biceps tendon (LHB) can deliver viable tenocytes for TTE. In this context,
      different isolation methods, such as enzymatic digestion (ED) and cell migration
      (CM), are investigated on differences in gene expression and cell morphology.
      METHODS: Samples of the LHB were obtained from patients, who underwent surgery
      for primary shoulder arthroplasty. Using ED as isolation method, 0.2% collagenase
      I solution was used. Using CM as isolation method, small pieces of minced tendon
      were put into petri-dishes. After cell cultivation, RT-PCR was performed for
      collagen type I, collagen type III, decorin, tenascin-C, fibronectin, Scleraxis,
      tenomodulin, osteopontin and agreccan. RESULTS: The total number of isolated
      cells, in relation to 1 g of native tissue, was 14 times higher using ED. The
      time interval for cell isolation was about 17 hours using ED and approximately 50
      days using CM. Cell morphology in vitro was similar for both isolation
      techniques. Higher expression of collagen type I could be observed in tenocyte
      like cell cultures (TLCC) using ED as isolation method (p < 0.05), however
      decorin expression was higher in TLCC using CM as isolation method (p < 0.05).
      Dedifferentiation potential seemed to be similar for both isolation techniques.
      CONCLUSION: In summary tenocyte-like cells can be obtained with both isolation
      methods (ED and CM) from the LHB. As no obvious disadvantage could be seen using
      ED, this method is more suitable for clinical use, as time for cell isolation is
      shorter and a remarkably higher number of cells can be obtained. However, both
      isolation methods can further be improved.

PMID- 22871217
TI  - Bioassay-guided isolation of prenylated xanthones and polycyclic
      acylphloroglucinols from the leaves of Garcinia nujiangensis.
AB  - Bioassay-guided fractionation of the acetone extract of the leaves of Garcinia
      nujiangensis resulted in the isolation of two new prenylated xanthones,
      nujiangexanthones A (1) and B (2), three new polycyclic polyprenylated
      acylphloroglucinols, nujiangefolins A-C (3-5), and 10 known related analogues.
      The structures of compounds 1-5 were elucidated by interpretation of their
      spectroscopic data. Compounds 3 and 4 are unusual polycyclic polyprenylated
      acylphloroglucinols in which the enol hydroxy group forms a six-membered ring
      with a benzene ring carbon. The compounds isolated were evaluated for their
      cytotoxic effects against 11 cancer cell lines and immortalized MIHA normal liver
      cells, and the test substances demonstrated selectivity toward the cancer cells.
      Isojacareubin (6) was found to be the most potent cytotoxic compound of those
      tested.

PMID- 22871218
TI  - Determination of 10 ginsenosides in Panax ginseng of different harvest times
      based on HPLC fingerprints and principal component analysis.
AB  - A combinative method of HPLC fingerprinting and quantitative determination was
      successfully applied to monitor dynamic accumulation of ginsenosides in five-year
      old Panax ginseng roots from different harvest times. The optimal chromatographic
      conditions were achieved on a C18 column with gradient elution using acetonitrile
      and 1 mmol . L(-1) KH2PO4 buffer solution at 203 nm. The result indicated that
      the contents of total ginsenosides showed significant variations, and a decrease
      tendency appeared in the growth period of the fifth year.

PMID- 22871219
TI  - Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine
      derivatives.
AB  - BACKGROUND: Imidazo[1,2-a]pyridines and pyrimidines are important organic
      fluorophores which have been investigated as biomarkers and photochemical
      sensors. The effect on the luminescent property by substituents in the
      heterocycle and phenyl rings, have been studied as well. In this investigation,
      series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were
      synthesized and evaluated in relation to fluorescence emission, based upon the
      hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence
      intensity. RESULTS: Compounds of both series emitted light in organic solvents
      dilutions as well as in acidic and alkaline media. Quantitative fluorescence
      spectroscopy determined that both fused heterocycles fluoresced more intensely
      than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3
      hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3
      hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer
      wavelengths, whereas the former emitted purple light. CONCLUSION: It was
      concluded that in most cases the hydroxymethyl moiety did act as an enhancer of
      the fluorescence intensity, however, a comparison made with the fluorescence
      emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the
      hydroxymethyl substituent decreased the fluorescence intensity.

PMID- 22871220
TI  - Sodium butyrate potentiates carbon tetrachloride-induced acute liver injury in
      mice.
AB  - Histone deacetylase 2 (HDAC2), a prominent member of the class I HDAC family,
      plays crucial roles in inflammation and other pathological processes. Recent
      studies have found that the activity and expression of HDAC2 were altered under
      oxidative stress conditions. The aim of the current study was to elucidate the
      expression and the possible pathophysiological significance of HDAC2 in CCl(4)
      induced oxidative hepatitis. Our resultant data indicated that the expression of
      HDAC2 in liver increased after CCl(4) exposure, which was attenuated by
      antioxidants N-acetyl-L-cysteine or alpha-lipoic acid. Administration of sodium
      butyrate (NaB), a representative HDAC inhibitor resulted in further elevation of
      serum aminotransferase levels, enhanced oxidative stress, reduced antioxidant
      enzyme activities, increased production of proinflammatory cytokines and
      aggravated hepatocellular necrosis as well as leukocyte infiltration in liver.
      The results suggested that oxidative stress in CCl(4)-exposed mice induce the
      expression of HDAC2, while inhibition of HDAC result in exacerbated liver injury.
      Therefore, HDAC might be involved in the pathogenesis of CCl(4)-induced liver
      injury and provide protective benefit.

PMID- 22871221
TI  - Biosecurity and the review and publication of dual-use research of concern.
AB  - Dual-use research of concern (DURC) is scientific research with significant
      potential for generating information that could be used to harm national
      security, the public health, or the environment. Editors responsible for journal
      policies and publication decisions play a vital role in ensuring that effective
      safeguards exist to cope with the risks of publishing scientific research with
      dual-use implications. We conducted an online survey of 127 chief editors of life
      science journals in 27 countries to examine their attitudes toward and experience
      with the review and publication of dual-use research of concern. Very few editors
      (11) had experience with biosecurity review, and no editor in our study reported
      having ever refused a submission on biosecurity grounds. Most respondents (74.8%)
      agreed that editors have a responsibility to consider biosecurity risks during
      the review process, but little consensus existed among editors on how to handle
      specific issues in the review and publication of research with potential dual-use
      implications. More work is needed to establish consensus on standards for the
      review and publication of dual-use research of concern in life science journals.

PMID- 22871222
TI  - Benzofuroquinoline derivatives had remarkable improvement of their selectivity
      for telomeric G-quadruplex DNA over duplex DNA upon introduction of peptidyl
      group.
AB  - In order to improve the selectivity of 5-N-methyl quindoline (cryptolepine)
      derivatives as telomeric quadruplex binding ligands versus duplex DNA, a series
      of peptidyl-benzofuroquinoline (P-BFQ) conjugates (2a-2n) were designed and
      synthesized. Their interactions with telomeric quadruplex and duplex DNA were
      examined by using the fluorescence resonance energy transfer (FRET) melting
      assay, surface plasmon resonance (SPR), circular dichroism spectroscopy (CD), and
      molecular modeling studies. Introduction of a peptidyl group at 11-position of
      the aromatic benzofuroquinoline scaffold not only effectively increased its
      binding affinity, but also significantly improved its selectivity toward
      telomeric quadruplex versus duplex DNA. Combined with the data for their
      inhibitory effects on telomerase activity, their structure-activity relationships
      (SARs) studies showed that the types of amino acid residues and the length of the
      peptidyl side chains were important for the improvement of their interactions
      with the telomeric G-quadruplex. Long-term exposure of human cancer cells to 2c
      showed a remarkable cessation in population growth and cellular senescence
      phenotype, and accompanied by a shortening of the telomere length.

PMID- 22871223
TI  - Synthesis and X-ray structures of novel macrocycles and macrobicycles containing
      N,N-di(pyrrolylmethyl)-N-methylamine moiety: preliminary anion binding study.
AB  - The [2 + 2] Schiff base condensation reactions between the newly synthesized
      dialdehyde, N,N-di(alpha-formylpyrrolyl-alpha-methyl)-N-methylamine), and
      ethylenediamine or p-phenylenediamine dihydrochloride readily afforded the 30-
      and 34-membered large size macrocycles in very high yields. Subsequent reduction
      reactions of these macrocycles with NaBH(4) gave the corresponding saturated
      macrocyclic hexaamines in good yields. The analogous reaction of the new
      dialdehyde with a triamine molecule afforded the [3 + 2] Schiff base macrobicycle
      in high yield, which was then reduced by reaction with NaBH(4) to give the
      saturated macrobicycle. All these compounds were characterized by spectroscopic
      methods. The anion binding properties of the saturated macrocycles having the
      ethylene and the phenylene linkers in CDCl(3) were studied by NMR titration
      methods. Although they have similar pyrrolic and amine NH groups their binding
      properties are different and interesting, owing to the conformational flexibility
      or rigidness rendered by the ethylene or phenylene groups, respectively. The
      macrocycle having the ethylene linkers binds anions in a 1:1 fashion, while the
      other receptor having the phenylene linkers prefers to bind anions in a
      sequential 1:2 fashion and has a multiple equilibria between a 1:1 and a 1:2
      complexes, as shown by their binding constants, curve fittings by EQNMR, and Job
      plots. The X-ray structures of the 1:2 methanol, the aqua and the benzoate anion
      complexes of the macrocycles show two cavities in which the guests are bound,
      correlating with the high affinity found for the formation of stable 1:2
      complexes in solution. The X-ray structure showed that the macrobicycle Schiff
      base adopts an eclipsed paddle-wheel shaped conformation and exhibits an out-out
      configuration at the bridgehead nitrogen atoms.

PMID- 22871224
TI  - Length of stay and cost for surgical site infection after abdominal and cardiac
      surgery in Japanese hospitals: multi-center surveillance.
AB  - PURPOSE: This study evaluated the influence of surgical site infections (SSIs)
      after abdominal or cardiac surgery on the post-operative duration of
      hospitalization and cost. METHODS: A retrospective 1:1 matched case-control study
      of length of stay and healthcare expenditures for patients who were discharged
      from nine hospitals, between April 1, 2006 and March 31, 2008, after undergoing
      abdominal or cardiac surgery and who did and did not have a SSI. RESULTS:
      Information was obtained from 246 pairs of patients who had undergone abdominal
      surgery and 27 pairs of patients who had undergone cardiac surgery. Overall, the
      mean post-operative hospitalization was 20.7 days longer and the mean post
      operative healthcare expenditure was $8,791 higher in the SSI group than for the
      SSI-free group. Among the patients who had undergone abdominal surgery,
      development of SSI extended the average hospitalization by 17.6 days and
      increased the average healthcare expenditure by $6,624. Among the patients who
      had undergone cardiac surgery, SSI extended the post-operative hospitalization by
      an average of 48.9 days and increased the post-operative healthcare expenditure
      by an average of $28,534. CONCLUSIONS: Under the current healthcare system in
      Japan, the development of SSI after abdominal surgery necessitates extension of
      hospitalization two-fold and increases the post-operative healthcare expenditure
      2.5-fold. Development of SSI after cardiac surgery necessitates extension of
      hospitalization fourfold and increases the healthcare expenditure six-fold.

PMID- 22871225
TI  - Children with paralytic poliomyelitis: utilization of physiotherapy services in
      Zamfara State, Nigeria.
AB  - Physiotherapy is usually indicated for health promotion and the rehabilitation of
      individuals with paralytic poliomyelitis. The endemic nature of this condition in
      children in Zamfara State, Nigeria necessitated investigation into the
      utilization of physiotherapy services by parents or primary caregivers of
      children affected with polio in this sub-region. Parents and primary caregivers
      of children with paralytic poliomyelitis were recruited using a purposive multi
      stage sampling procedure in a cross-sectional survey. Factors associated with the
      utilization of physiotherapy services were assessed based on questions extracted
      from a 4-part, 52-item structured questionnaire originally designed for a study
      which investigated knowledge, attitude, and beliefs of parents of children with
      paralytic poliomyelitis. A total of 217 participants were included in this study.
      The mean age was 32.29 +/- 9.89 years and the mean knowledge of polio score was
      62.0 +/- 17.3%. The mean age of the children with paralytic poliomyelitis was
      6.41 +/- 2.50 years. Only 27.2% of the parents or primary caregivers had utilized
      physiotherapy service for their children at some point. No association existed
      between utilization of physiotherapy service and 'knowledge of paralytic
      poliomyelitis', 'employment status', and 'family income' of respondents.
      Explanations for low utilization of physiotherapy services for children with
      paralytic poliomyelitis by parents or primary caregivers are discussed.

PMID- 22871226
TI  - Analysis of 777 cases with obstruction of the ureter or extrahepatic bile duct by
      ultrasonography after normal saline retention enema.
AB  - BACKGROUND: Conventional transabdominal ultrasound usually fails to visualize
      parts of the ureter or extrahepatic bile duct covered by bowel gas. In this
      study, we propose a new method for gaining acoustic access to the ureters and
      extrahepatic bile duct to help determine the nature of obstruction to these
      structures when conventional transabdominal ultrasound fails. METHODS: The normal
      saline retention enema method, that is, using normal saline-filled colons to gain
      acoustic access to the bilateral ureters and extrahepatic bile duct and detecting
      the lesions with transabdominal ultrasonic diagnostic apparatus, was applied to
      777 patients with obstructive lesions, including 603 with hydroureter and 174
      with dilated common bile duct, which were not visualized by conventional
      ultrasonography. The follow-up data of all the patients were collected to verify
      the results obtained by this method. RESULTS: Of the 755 patients who
      successfully finished the examination after normal saline retention enema (the
      success rate of the enema is about 98%), the nature of obstruction in 718
      patients was determined (the visualizing rate is approximately 95%), including
      533 with ureteral calculus, 23 with ureteral stricture, 129 with extrahepatic
      bile duct calculus, and 33 with common bile duct tumor. CONCLUSIONS: Colons
      filled fully with normal saline can surely give acoustic access to the bilateral
      ureters and extrahepatic bile duct so as to determine the nature of obstruction
      of these structures when conventional transabdominal ultrasound fails.

PMID- 22871227
TI  - Characterization of extended-spectrum beta-lactamase-producing Salmonella
      enterica serotype Brunei and Heidelberg at the Hussein Dey hospital in Algiers
      (Algeria).
AB  - The purpose of this work was to study the genetic determinants responsible for
      extended-spectrum cephalosporin (ESC) resistance of Salmonella collected during
      the period of 1995-2008 at the Hussein Dey hospital in Algiers (Algeria).
      Fourteen ESC-resistant Salmonella isolates were tested towards 22 antimicrobial
      agents. Polymerase chain reaction (PCR) and sequencing were used to determine the
      underlying genetic determinants responsible for the extended-spectrum beta
      lactamase (ESBL) phenotypes. Enterobacterial Repetitive Intergenic Consensus PCR
      was employed to type the isolates. All tested isolates were resistant to
      ticarcillin, ticarcillin-clavulanate, piperacillin, cefuroxime, aztreonam,
      ceftazidime, cefotaxime (except two isolates), cefepime, and cefpirome. PCR and
      DNA sequencing identified these ESBLs as TEM-48 (n=6), TEM-4 (n=3), CTX-M-15
      (n=4), and one new TEM, designated TEM-188. Thus, continued surveillance for the
      presence of ESBL-producing (non-typhoidal) salmonellae in Algeria is essential.

PMID- 22871228
TI  - Treatment with gabapentin associated with resolution of apnea in two infants with
      neurologic impairment.
AB  - BACKGROUND: Infants with neurologic impairment (NI) as a result of injury to the
      central nervous system have a significant rate of pain. Problems associated with
      pain in children with NI include increased tone. This secondary hypertonia may
      contribute to apnea as a result of alterations in airway tone and chest wall
      movement. Infants are at greatest risk given their smaller airways, lower
      functional residual capacity, and the high rate of unrecognized pain at this age.
      DISCUSSION: We report two cases of infants with NI, identified to have
      significant improvement in apnea following empiric treatment with gabapentin for
      presumed central pain and/or visceral hyperalgesia. This correlation between pain
      and apnea, with resolution in apnea following effective treatment of these
      presumed sources, has not been previously reported in the literature. CONCLUSION:
      Infants with NI and apnea should have careful pain assessment and treatment, when
      considering other causes and interventions for apnea.

PMID- 22871230
TI  - Pilot study of a model-based approach to blood glucose control in very-low
      birthweight neonates.
AB  - BACKGROUND: Hyperglycemia often occurs in premature, very low birthweight infants
      (VLBW) due to immaturity of endogenous regulatory systems and the stress of their
      condition. Hyperglycemia in neonates has been linked to increased morbidities and
      mortality and occurs at increasing rates with decreasing birthweight. In this
      cohort, the emerging use of insulin to manage hyperglycemia has carried a
      significant risk of hypoglycemia. The efficacy of blood glucose control using a
      computer metabolic system model to determine insulin infusion rates was assessed
      in very-low-birth-weight infants. METHODS: Initial short-term 24-hour trials were
      performed on 8 VLBW infants with hyperglycemia followed by long-term trials of
      several days performed on 22 infants. Median birthweight was 745 g and 760 g for
      short-term and long-term trial infants, and median gestational age at birth was
      25.6 and 25.4 weeks respectively. Blood glucose control is compared to 21
      retrospective patients from the same unit who received insulin infusions
      determined by sliding scales and clinician intuition. This study was approved by
      the Upper South A Regional Ethics Committee, New Zealand (ClinicalTrials.gov
      registration NCT01419873). RESULTS: Reduction in hyperglycemia towards the target
      glucose band was achieved safely in all cases during the short-term trials with
      no hypoglycemic episodes. Lower median blood glucose concentration was achieved
      during clinical implementation at 6.6 mmol/L (IQR: 5.5 - 8.2 mmol/L, 1,003
      measurements), compared to 8.0 mmol/L achieved in similar infants previously (p <
      0.01). No significant difference in incidence of hypoglycemia during long-term
      trials was observed (0.25% vs 0.25%, p = 0.51). Percentage of blood glucose
      within the 4.0 - 8.0 mmol/L range was increased by 41% compared to the
      retrospective cohort (68.4% vs 48.4%, p < 0.01). CONCLUSIONS: A computer model
      that accurately captures the dynamics of neonatal metabolism can provide safe and
      effective blood glucose control without increasing hypoglycemia. TRIAL
      REGISTRATION: ClinicalTrials.gov registration NCT01419873.

PMID- 22871231
TI  - Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes.
AB  - Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist
      whose receptors are overexpressed on tumor cells, with [PtCl(2)(dap)] (dap = 1
      (carboxylic acid)-1,2-diaminoethane) (3), [(eta(6)-bip)Os(4-CO(2)-pico)Cl] (bip =
      biphenyl, pico = picolinate) (4), [(eta(6)-p-cym)RuCl(dap)](+) (p-cym = p-cymene)
      (5), and [(eta(6)-p-cym)RuCl(imidazole-CO(2)H)(PPh(3))](+) (6), were synthesized
      by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and
      DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR
      spectroscopy and molecular dynamics calculations showed that conjugate formation
      does not perturb the overall peptide structure. Only 6 exhibited
      antiproliferative activity in human tumor cells (IC(50) = 63 +/- 2 MUM in MCF-7
      cells and IC(50) = 26 +/- 3 MUM in DU-145 cells) with active participation of
      somatostatin receptors in cellular uptake. Similar cytotoxic activity was found
      in a normal cell line (IC(50) = 45 +/- 2.6 MUM in CHO cells), which can be
      attributed to a similar level of expression of somatostatin subtype-2 receptor.
      These studies provide new insights into the effect of receptor-binding peptide
      conjugation on the activity of metal-based anticancer drugs, and demonstrate the
      potential of such hybrid compounds to target tumor cells specifically.

PMID- 22871232
TI  - Effect of tramadol on behavioral alterations and lipid peroxidation after
      transient forebrain ischemia in rats.
AB  - N-methyl-D-aspartate (NMDA) antagonists and gamma-aminobutyric acid (GABA)
      agonists are proven protective in various animal models of ischemic brain damage.
      Tramadol, a centrally acting opioid analgesic reportedly possesses NMDA
      antagonistic and GABA agonistic properties, with additional ion channel blocking
      activity. The aim of the present study was to evaluate the possible
      neuroprotective effect of tramadol hydrochloride in a rat model of transient
      forebrain ischemia. Male Wistar rats were pretreated with tramadol hydrochloride
      at doses of 10 and 20 mg/kg b.w. intraperitoneally for 4 days and were subjected
      to 30 min occlusion of bilateral common carotid arteries followed by reperfusion
      for 24 h. Impairment in sensorimotor functions was evaluated by beam walking
      task, spontaneous locomotor activity and hanging wire test. Animals were
      sacrificed and the brain homogenates were used for estimating the levels of lipid
      peroxidation, a marker for extent of oxidative stress. Ischemic rats exhibited a
      significant decrease in locomotion, grip strength and increase in beam walking
      latency. Tramadol attenuated the post ischemic motor impairment evidenced by
      improvement in the performance in sensorimotor tests. The extent of lipid
      peroxidation was significantly (p < 0.001) reduced by tramadol pretreatment which
      was higher in ischemic control. This study demonstrates the neuroprotective
      effect of tramadol against transient forebrain ischemia in rats.

PMID- 22871233
TI  - Isoflavones suppress the expression of the FcepsilonRI high-affinity
      immunoglobulin E receptor independent of the estrogen receptor.
AB  - Isoflavones found in soybeans and soy products possess clinically relevant
      properties. However, the anti-allergic effect of isoflavones has been poorly
      studied. We examined the effects of isoflavones, genistein, daidzein, and equol,
      on the expression of the high-affinity immunoglobulin E (IgE) receptor,
      FcepsilonRI, which plays a central role in IgE-mediated allergic response. Flow
      cytometric analysis showed that all of these isoflavones reduced the cell surface
      expression of FcepsilonRI on mouse bone-marrow-derived mast cells and human
      basophilic KU812 cells. All isoflavones decreased the levels of the
      FcepsilonRIalpha mRNA in the cells. Genistein reduced the mRNA expression of the
      beta chain, and daidzein and equol downregulated that of the gamma chain. The
      suppressive effects of isoflavones on FcepsilonRI expression were unaffected by
      ICI 182,780, an estrogen receptor antagonist, suggesting that these effects were
      independent of estrogen receptors. 

PMID- 22871234
TI  - Simple and fast HPLC method for simultaneous determination of retinol,
      tocopherols, coenzyme Q(10) and carotenoids in complex samples.
AB  - The effects of fat-soluble vitamins (such as vitamins A and E) and lipid
      microconstituents (such as carotenoids) on human health are now well established.
      However, high-performance liquid chromatography (HPLC) methods able to detect
      these molecules in simultaneous runs are often difficult to set up. We report
      here a 35-min reversed-phase HPLC method using a single C30 column kept at 35
      degrees C with a gradient system of methanol, methyl-tert-butyl ether and water
      at a flow-rate of 1 mL/min. This method resolves 11 carotenoids, retinol, alpha-
      and gamma-tocopherol from complex matrixes such as food samples, human plasma and
      human adipose tissue within 35 min. The method is also able to separate coenzyme
      Q(10). The intra-day and inter-day coefficients of variation are suitable for
      routine clinical and scientific applications for the determination of lipid
      micronutrients from various sample types.

PMID- 22871235
TI  - Total synthesis of aspercyclides A and B via intramolecular oxidative diaryl
      ether formation.
AB  - A highly efficient total synthesis of the 11-membered cyclic aspercyclides A (1)
      and B (2) has been achieved by chemo- and regioselective intramolecular oxidative
      C-O bond formation from differently substituted diphenols.

PMID- 22871236
TI  - Proteinases as virulence factors in Leishmania spp. infection in mammals.
AB  - Leishmania parasites cause human tegumentary and visceral infections that are
      commonly referred to as leishmaniasis. Despite the high incidence and prevalence
      of cases, leishmaniasis has been a neglected disease because it mainly affects
      developing countries. The data obtained from the analysis of patients' biological
      samples and from assays with animal models confirm the involvement of an array of
      the parasite's components in its survival inside the mammalian host. These
      components are classified as virulence factors. In this review, we focus on
      studies that have explored the role of proteinases as virulence factors that
      promote parasite survival and immune modulation in the mammalian host.
      Additionally, the direct involvement of proteinases from the host in lesion
      evolution is analyzed. The gathered data shows that both parasite and host
      proteinases are involved in the clinical manifestation of leishmaniasis. It is
      interesting to note that although the majority of the classes of proteinases are
      present in Leishmania spp., only cysteine-proteinases, metalloproteinases and, to
      a lesser scale, serine-proteinases have been adequately studied. Members from
      these classes have been implicated in tissue invasion, survival in macrophages
      and immune modulation by parasites. This review reinforces the importance of the
      parasite proteinases, which are interesting candidates for new chemo or
      immunotherapies, in the clinical manifestations of leishmaniasis.

PMID- 22871237
TI  - Differences in implementation of gait analysis recommendations based on
      affiliation with a gait laboratory.
AB  - This study examined the extent to which gait analysis recommendations are
      followed by orthopedic surgeons with varying degrees of affiliation with the gait
      laboratory. Surgical data were retrospectively examined for 95 patients with
      cerebral palsy who underwent lower extremity orthopedic surgery following gait
      analysis. Thirty-three patients were referred by two surgeons directly affiliated
      with the gait laboratory (direct affiliation), 44 were referred by five surgeons
      from the same institution but not directly affiliated with the gait laboratory
      (institutional affiliation), and 18 were referred by 10 surgeons from other
      institutions (no affiliation). Data on specific surgeries were collected from the
      gait analysis referral, gait analysis report, and operative notes. Adherence to
      the gait analysis recommendations was calculated by dividing the number of
      procedures where the surgery followed the gait analysis recommendation
      (numerator) by the total number of procedures initially planned, recommended by
      gait analysis, or done (denominator). Adherence with the gait analysis
      recommendations was 97%, 94%, and 77% for the direct, institutional, and no
      affiliation groups, respectively. Procedures recommended for additions to the
      surgical plan were added 98%, 87%, and 77% of the time. Procedures recommended
      for elimination were dropped 100%, 89%, and 88% of the time. Of 81 patients who
      had specific surgical plans prior to gait analysis, changes were implemented in
      84% (68/81) following gait analysis recommendations. Gait analysis influences the
      treatment decisions of surgeons regardless of affiliation with the gait
      laboratory, although the influence is stronger for surgeons who practice within
      the same institution as the gait laboratory.

PMID- 22871238
TI  - Music and metronome cues produce different effects on gait spatiotemporal
      measures but not gait variability in healthy older adults.
AB  - Rhythmic auditory cues including music and metronome beats have been used,
      sometimes interchangeably, to improve disordered gait arising from a range of
      clinical conditions. There has been limited investigation into whether there are
      optimal cue types. Different cue types have produced inconsistent effects across
      groups which differed in both age and clinical condition. The possible effect of
      normal ageing on response to different cue types has not been reported for gait.
      The aim of this study was to determine the effects of both rhythmic music and
      metronome cues on gait spatiotemporal measures (including variability) in healthy
      older people. Twelve women and seven men (>65 years) walked on an instrumented
      walkway at comfortable pace and then in time to each of rhythmic music and
      metronome cues at comfortable pace stepping frequency. Music but not metronome
      cues produced a significant increase in group mean gait velocity of 4.6 cm/s, due
      mostly to a significant increase in group mean stride length of 3.1cm. Both cue
      types produced a significant but small increase in cadence of 1 step/min. Mean
      spatio-temporal variability was low at baseline and did not increase with either
      cue type suggesting cues did not disrupt gait timing. Study findings suggest
      music and metronome cues may not be used interchangeably and cue type as well as
      frequency should be considered when evaluating effects of rhythmic auditory
      cueing on gait. Further work is required to determine whether optimal cue types
      and frequencies to improve walking in different clinical groups can be
      identified.

PMID- 22871239
TI  - Lung dose calculation with SPECT/CT for 90Yittrium radioembolization of liver
      cancer.
AB  - PURPOSE: To propose a new method to estimate lung mean dose (LMD) using
      technetium-99m labeled macroaggregated albumin ((99m)Tc-MAA) single photon
      emission CT (SPECT)/CT for (90)Yttrium radioembolization of liver tumors and to
      compare the LMD estimated using SPECT/CT with clinical estimates of LMD using
      planar gamma scintigraphy (PS). METHODS AND MATERIALS: Images of 71 patients who
      had SPECT/CT and PS images of (99m)Tc-MAA acquired before TheraSphere
      radioembolization of liver cancer were analyzed retrospectively. LMD was
      calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy
      per GBq of injected activity shunted to the lung. For the SPECT/CT-based
      estimate, the LMD was calculated with the activity concentration and lung volume
      derived from SPECT/CT. The effect of attenuation correction and the patient's
      breathing on the calculated LMD was studied with the SPECT/CT. With these effects
      correctly taken into account in a more rigorous fashion, we compared the LMD
      calculated with SPECT/CT with the LMD calculated with PS. RESULTS: The mean dose
      to the central region of the lung leads to a more accurate estimate of LMD.
      Inclusion of the lung region around the diaphragm in the calculation leads to an
      overestimate of LMD due to the misregistration of the liver activity to the lung
      from the patient's breathing. LMD calculated based on PS is a poor predictor of
      the actual LMD. For the subpopulation with large lung shunt, the mean
      overestimation from the PS method for the lung shunt was 170%. CONCLUSIONS: A new
      method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization
      of liver cancer based on (99m)Tc-MAA SPECT/CT is presented. The new method
      provides a more accurate estimate of radiation risk to the lungs. For patients
      with a large lung shunt calculated from PS, a recalculation of LMD based on
      SPECT/CT is recommended.

PMID- 22871240
TI  - Evaluation and treatment of respiratory alkalosis.
AB  - Respiratory alkalosis is the most frequent acid-base disturbance encountered in
      clinical practice. This is particularly true in critically ill patients, for whom
      the degree of hypocapnia directly correlates with adverse outcomes. Although this
      acid-base disturbance often is considered benign, evidence suggests that the
      alkalemia of primary hypocapnia can cause clinically significant decreases in
      tissue oxygen delivery. Mild respiratory alkalosis often serves as a marker of an
      underlying disease and may not require therapeutic intervention. In contrast,
      severe respiratory alkalosis should be approached with a sense of urgency and be
      aggressively corrected.

PMID- 22871242
TI  - Human adipose-derived stem cells enhance the angiogenic potential of endothelial
      progenitor cells, but not of human umbilical vein endothelial cells.
AB  - One of the current challenges in the field of adipose tissue engineering is to
      promote sufficient vascularization to prevent cell death and to support adipose
      tissue formation. Thus, a novel strategy to enhance neovascularization of tissue
      engineered adipose tissue might be the coimplantation of adipose-derived stem
      cells (ASCs) with endothelial progenitor cells (EPCs). However, no knowledge is
      given about the cellular interaction in vitro of human ASCs derived from
      subcutaneous fat tissue and EPCs derived from human peripheral blood. In this
      study, the first aim was to characterize ASCs and EPCs. Secondly, the two
      dimensional Matrigel assay and the three-dimensional spheroid sprouting assay
      were applied for analyzing the ASC-EPC interaction in regard to formation of
      capillary-like structures by EPCs by ASC-conditioned medium (CM) or coculture of
      both cell types and compared to cocultures of ASCs and human umbilical vein
      endothelial cells (HUVECs). ASC-CM had no influence on the formation of capillary
      like structures by EPCs. However, coculture with ASCs significantly enhanced the
      formation of capillary-like structures by EPCs; an effect that was not observed
      in cocultures of ASCs with HUVECs. Importantly, this increase in capillary-like
      structure formation by EPCs due to cell-cell contact was associated with
      significantly increased vascular endothelial growth factor (VEGF) secretion and
      VEGF-A mRNA expression, while inhibition of VEGF receptor tyrosine kinases
      completely abolished this effect. In conclusion, these data suggest that cellular
      communication occurs between ASCs and EPCs triggered by cell-cell contact or at
      least close proximity, which is partially mediated by secreted VEGF leading to
      the enhancement of angiogenic properties in EPCs, but not in HUVECs.

PMID- 22871243
TI  - Total calcium absorption is similar from infant formulas with and without
      prebiotics and exceeds that in human milk-fed infants.
AB  - BACKGROUND: 1) To evaluate calcium absorption in infants fed a formula containing
      prebiotics (PF) and one without prebiotics (CF). 2) To compare calcium absorption
      from these formulas with a group of human milk-fed (HM) infants. METHODS: A dual
      tracer stable isotope method was used to assess calcium absorption in infants
      exclusively fed CF (n = 30), PF (n = 25) or HM (n = 19). Analysis of variance was
      used to analyze calcium intake, fractional calcium absorption, and the amount of
      calcium absorbed. RESULTS: Calcium intake (Mean +/- SEM) for PF was 534 +/- 17
      mg/d and 557 +/- 16 mg/d for CF (p = 0.33). Fractional calcium absorption was
      56.8 +/- 2.6 % for PF and 59.2 +/- 2.3 % for CF (p = 0.49). Total calcium
      absorbed for PF was 300 +/- 14 mg/d and 328 +/- 13 mg/d for CF (p = 0.16). For HM
      infants calcium intake was 246 +/- 20 mg/d, fractional calcium absorption was
      76.0 +/- 2.9 % and total calcium absorbed was 187 +/- 16 mg/d (p <0.001, compared
      to either PF or CF). CONCLUSIONS: Despite lower fractional calcium absorption of
      CF and PF compared to HM, higher calcium content in both led to higher total
      calcium absorption compared to HM infants. No significant effect of prebiotics
      was observed on calcium absorption or other markers of bone mineral metabolism.

PMID- 22871244
TI  - [Prednisone for rheumatoid arthritis: the detriment of the doubt].
AB  - Physicians pride themselves on practicing evidence-based medicine. However, these
      principles appear not to apply in the case of glucocorticoid therapy for
      rheumatoid arthritis (RA). Despite a sizable body of evidence, glucocorticoids
      are underutilised in the treatment of RA. Hench's 1950 acceptance speech for the
      Nobel Prize (which he shared with Kendall and Reichstein for the discovery of
      glucocorticoids) illustrated his awareness of the benefits and risks of these
      agents. Although glucocorticoids have proved beneficial in randomized trials from
      1955 onwards, only a perception of harm has endured. The recently published
      CAMERA-2 trial data could be the final piece of evidence added to the substantial
      body of literature proving that prednisone 10 mg/d given for 2 years in early RA,
      in addition to high-dose methotrexate, is better than methotrexate alone in
      inducing remission and preventing joint damage, and is accompanied by fewer side
      effects. Existing treatment guidelines need to be urgently updated to reflect
      these findings.

PMID- 22871245
TI  - [A woman with a biting arthropod].
AB  - A 36-year-old woman presented with a red, itching bump on her back and brought
      the arthropod that had bitten her. The diagnosis, a bite of a soft tick, was made
      by determination of the arthropod as a pigeon tick (Argas reflexus). Pigeon ticks
      only occasionally bite humans and can transmit multiple infectious diseases.

PMID- 22871246
TI  - [Metal fume fever, often unrecognized].
AB  - BACKGROUND: Metal fume fever is an occupational disease caused by inhalation of
      volatile metal oxides. Clinically there is a strong resemblance to influenza. It
      is thought that metal fume fever occurs much more frequently than it is reported.
      The symptoms are self-limiting without treatment, disappearing within 24-48 hours
      without residual symptoms. CASE DESCRIPTION: A male 35-year-old construction
      worker had cut galvanized steel plates in a closed environment. He had a flu-like
      illness with fever, leucocytosis and hypoxemia. The symptoms resolved completely
      without treatment within 18 hours. CONCLUSION: Metal fume fever is a frequently
      occurring disease but is often overlooked. It is important to ask about exposure
      to metal fumes in certain occupational groups in order to make the correct
      diagnosis. In this way measures can be taken to avoid exposure to metal oxides
      and to prevent recurrence of the disease.

PMID- 22871241
TI  - Nitric oxide synthases in heart failure.
AB  - SIGNIFICANCE: The regulation of myocardial function by constitutive nitric oxide
      synthases (NOS) is important for the maintenance of myocardial Ca(2+)
      homeostasis, relaxation and distensibility, and protection from arrhythmia and
      abnormal stress stimuli. However, sustained insults such as diabetes,
      hypertension, hemodynamic overload, and atrial fibrillation lead to dysfunctional
      NOS activity with superoxide produced instead of NO and worse pathophysiology.
      RECENT ADVANCES: Major strides in understanding the role of normal and abnormal
      constitutive NOS in the heart have revealed molecular targets by which NO
      modulates myocyte function and morphology, the role and nature of post
      translational modifications of NOS, and factors controlling nitroso-redox
      balance. Localized and differential signaling from NOS1 (neuronal) versus NOS3
      (endothelial) isoforms are being identified, as are methods to restore NOS
      function in heart disease. CRITICAL ISSUES: Abnormal NOS signaling plays a key
      role in many cardiac disorders, while targeted modulation may potentially reverse
      this pathogenic source of oxidative stress. FUTURE DIRECTIONS: Improvements in
      the clinical translation of potent modulators of NOS function/dysfunction may
      ultimately provide a powerful new treatment for many hearts diseases that are
      fueled by nitroso-redox imbalance.

PMID- 22871247
TI  - [Obesity caused by melanocortin-4 receptor mutations].
AB  - Obesity is usually the result of a combination of genetic and lifestyle factors.
      In monogenic obesity, overweight is caused by a single gene mutation. The most
      frequent form of monogenic obesity is caused by mutations in the gene that codes
      for the melanocortin-4 receptor (MC4R gene). Approximately 2% of Dutch children
      with obesity have a mutation in the MC4R gene. Children with homozygous and
      'compound' heterozygous MC4R mutations have a phenotype distinguished by extreme
      overweight at an early age and hyperphagia. Children with heterozygous MC4R
      mutations have a more subtle phenotype and are difficult to distinguish
      clinically from obese children without this mutation. MC4R mutations can be
      identified by DNA diagnostics.- Drug treatment is not yet available for this
      condition.

PMID- 22871249
TI  - [Thomas Addison and the adrenal gland].
AB  - The famous and beautifully illustrated monograph "On the Constitutional and Local
      Effects of Disease of the Suprarenal Capsules" was published by Thomas Addison in
      1855. This was the first description of the disease that now bears his name.
      Thomas Addison provided the first real contribution to the knowledge of adrenal
      function after three centuries of non-productive speculation and is one of the
      founders of modern endocrinology.

PMID- 22871251
TI  - [Non-responsive coeliac disease: what to do?].
AB  - Coeliac disease (CD) is the most common cause of villous atrophy and is
      increasingly recognized. The majority of CD patients responds to a gluten-free
      diet (GFD). However, some patients experience persistence or recurrence of
      symptoms despite a GFD. These patients require further diagnostic workup. We
      describe a 62-year-old female with recurring symptoms attributed to refractory
      coeliac disease (RCD) type I. A 66-year-old patient with a similar history had
      aberrant intraepithelial lymphocytes characteristic for RCD type II in her
      duodenum. Furthermore, in a third CD patient described here, microscopic colitis
      was responsible for diarrhoea that persisted despite strict dietary adherence.
      Microscopic colitis is strongly associated with CD and should be considered in
      patients with this disease. On the basis of these three illustrative case
      studies, we discuss the causes of non-responsive CD and their respective
      diagnostic workup.

PMID- 22871252
TI  - [The centralisation of highly complex operations].
AB  - The relationship between hospital volume and outcome of care after pancreatic
      surgery, particularly mortality, has been described extensively in the past.
      Today, this relationship is frequently being used by healthcare providers and/or
      insurance companies to select hospitals for various surgical procedures. This
      concept, however, has many limitations. The conceptual model concerning the
      relationship between how hospital facilities are arranged and the different
      aspects of the process of providing healthcare is discussed in three case
      histories describing complicated postoperative courses after pancreatic
      resections. The conclusion is that, besides hospital volume, the manner in which
      the various facilities in hospitals are arranged as well as the process of care
      giving, particularly the effectiveness of multidisciplinary meetings, are of
      crucial importance to the quality of care. Data per illness, with adequate
      correction for case mix, are of crucial importance for comparing the differences
      in quality of care between hospitals.

PMID- 22871253
TI  - Phosphate recovery by high flux low pressure multilayer membranes.
AB  - This work illustrates the potential use of PEI/PSS bilayers assembled via layer
      by layer (lbl) method on a nylon microfiltration membrane for the recovery of
      phosphate from water in the presence of chloride under ultrafiltration
      conditions. A total of nine bilayers were used for the selective recovery of
      phosphate. Bilayers were constructed from polyelectrolyte solutions of varying
      ionic strength (0-1 M of NaCl). The selected pH for deposition of PEI (5.9) and
      the presence of supporting salt in the polyelectrolyte solution is expected to
      provide membranes with high permeability and high charge density. This particular
      combination of bilayers yielded high flux membranes that allowed selective
      removal of H(2)PO(4)(-) in the presence of Cl(-) at low pressure (0.28 bar). The
      magnitude of negative solute rejection of chloride showed increasing trend with
      the number of bilayer for a particular salt concentration. Whereas the increase
      in magnitude with ionic strength is so high (-6.18 to -269.17 at 0.5 M NaCl for 9
      bl) that gave the best observed Cl(-)/H(2)PO(4)(-) selectivity (310.23, flux
      13.53 m(3)/m(2)-day). To the best of our knowledge, this is the first time a
      multilayer polyelectrolyte system with such a high selectivity and rejection for
      H(2)PO(4)(-) is reported. The solution flux decreased with the number of bilayers
      and ionic strength. The rejection of phosphate was dependent on feed pH,
      concentration of deposited polyelectrolyte solution, and composition of membrane
      support.

PMID- 22871254
TI  - Psychosocial adjustment of epilepsy patients in Cyprus.
AB  - This study investigated aspects of psychosocial adjustment in epilepsy patients
      in Cyprus. Sixty-three patients under 55 years of age with idiopathic or
      symptomatic epilepsy and 89 neurologically matched healthy volunteers
      participated. Subjects completed the State and Trait Anxiety Inventory and the
      Beck Depression Inventory; patients with epilepsy also completed the Epilepsy
      Foundation Concerns Index. Results showed that patients with symptomatic epilepsy
      had significantly higher scores on state and trait anxiety and depressive
      symptoms. Sociodemographic characteristics including gender, marital status, and
      education levels contributed to differences in trait and state anxiety,
      depressive symptom scales, autonomy concerns, and fear for seizure recurrence.
      Variables such as poor seizure control and use of polytherapy were associated
      with lower adjustment scores and reduced psychosocial outcome. Finally, patients
      with epilepsy scored significantly higher on depression and anxiety symptoms. The
      results provide further evidence on challenges patients with epilepsy face and on
      the need for implementing psychosocial prevention programs.

PMID- 22871255
TI  - Antioxidant activities of extracts from teas prepared from medicinal plants,
      Morus alba L., Camellia sinensis L., and Cudrania tricuspidata , and their
      volatile components.
AB  - The antioxidant activity of essences of teas prepared from mulberry ( Morus alba 
      L.),  Camellia sinensis  L., and  Cudrania tricuspidata  (Carr.) Burea plant was
      examined using two antioxidant assays. Selected volatile chemicals identified in
      these plants were also tested for antioxidant activity. All extracts exhibited
      antioxidant activity with a clear dose response in the aldehyde/carboxylic acid
      and the malonaldehyde/gas chromatography (MA/GC) assays. Antioxidant activity of
      extracts at the level of 500 MUg/mL ranged from 77.02 +/- 0.51% (stems of Burea
      plant) to 52.57 +/- 0.92% (fermented tea of  Camellia  and stems of Mulberry tea)
      in the aldehydes/carboxylic acid assay. Their antioxidant activity at the level
      of 160 MUg/mL ranged from 76.17 +/- 0.27% (roots of Burea plant) to 59.32 +/-
      0.27% (stems of Mulberry tea) in the MA/GC assay. Among the positively identified
      compounds (11 terpenes and terpenoids, 15 alkyl compounds, 26 nitrogen containing
      heterocyclic compounds, 9 oxygen containing heterocyclic compounds, 18 aromatic
      compounds, 7 lactones, 6 acids, and 4 miscellaneous compounds), eugenol, 2,5
      dihydroxyl acetophenone, and isoeugenol exhibited antioxidant activity comparable
      to that of BHT in both assays. Vanillin and 2-acetylpyrrole showed potent
      antioxidant activity in the aldehydes/carboxylic acid assay but only moderate
      activity in the MA/GC assay. These results suggest that consumption of
      antioxidant-rich beverages prepared from these plants may be beneficial to human
      health.

PMID- 22871256
TI  - Conscious sedation or general anaesthetic for intramuscular botulinum toxin
      injections in children - a two centre cross-sectional prospective audit.

PMID- 22871257
TI  - Behavioral sensitization to ethanol results in cross-sensitization to MK-801 but
      not to NMDA administered intra-accumbens.
AB  - In mice, repeated ethanol administration may induce behavioral sensitization - a
      process of progressive potentiation of its stimulant effects, associated with
      neuroadaptations in the brain reward system. Few studies have directly
      investigated the subsequent neuroadaptations in the nucleus accumbens (NAc), the
      central area of the brain reward system, after chronic ethanol administration.
      The goal of the present study was to analyze the involvement of accumbal
      glutamate NMDA receptors in the locomotion behavioral response to an NMDA agonist
      or to an NMDA antagonist in mice previously treated with ethanol. Swiss Albino
      mice received repeated daily administrations of 2.2 g/kg ethanol or saline for 21
      days. According to their locomotor response on the last day of treatment, ethanol
      treated mice were classified into sensitized or non-sensitized groups. They were
      then submitted to a surgical procedure to implement intra-NAc cannulae. After
      recovery, mice were challenged with intra-NAc administration of saline and, two
      days later, with NMDA (NMDA agonist) or MK-801 (NMDA antagonist), having their
      locomotor activity recorded for 1 h. The administration of NMDA induced similar
      locomotor behavior in all groups. On the other hand, the administration of 3
      MUg/side MK-801 induced a significant stimulant effect which was more prominent
      during the first 15 min in the sensitized group than in the non-sensitized or
      saline groups. Despite no effect of the agonist administration, only in
      sensitized mice did we observe cross-sensitization between repeated ethanol
      treatment and the intra-NAc administration of MK-801.

PMID- 22871258
TI  - Molecular characterization of the hexose transporter gene in benznidazole
      resistant and susceptible populations of Trypanosoma cruzi.
AB  - BACKGROUND: Hexose transporters (HT) are membrane proteins involved in the uptake
      of energy-supplying glucose and other hexoses into the cell. Previous studies
      employing the Differential Display technique have shown that the transcription
      level of the HT gene from T. cruzi (TcrHT) is higher in an in vitro-induced
      benznidazole (BZ)-resistant population of the parasite (17 LER) than in its
      susceptible counterpart (17 WTS). METHODS: In the present study, TcrHT has been
      characterized in populations and strains of T. cruzi that are resistant or
      susceptible to BZ. We investigated the copy number and chromosomal location of
      the gene, the levels of TcrHT mRNA and of TcrHT activity, and the phylogenetic
      relationship between TcrHT and HTs from other organisms. RESULTS: In silico
      analyses revealed that 15 sequences of the TcrHT gene are present in the T. cruzi
      genome, considering both CL Brener haplotypes. Southern blot analyses confirmed
      that the gene is present as a multicopy tandem array and indicated a nucleotide
      sequence polymorphism associated to T. cruzi group I or II. Karyotype analyses
      revealed that TcrHT is located in two chromosomal bands varying in size from 1.85
      to 2.6 Mb depending on the strain of T. cruzi. The sequence of amino acids in the
      HT from T. cruzi is closely related to the HT sequences of Leishmania species
      according to phylogenetic analysis. Northern blot and quantitative real-time
      reverse transcriptase polymerase chain reaction analyses revealed that TcrHT
      transcripts are 2.6-fold higher in the resistant 17 LER population than in the
      susceptible 17 WTS. Interestingly, the hexose transporter activity was 40% lower
      in the 17 LER population than in all other T. cruzi samples analyzed. This
      phenotype was detected only in the in vitro-induced BZ resistant population, but
      not in the in vivo-selected or naturally BZ resistant T. cruzi samples.
      Sequencing analysis revealed that the amino acid sequences of the TcrHT from
      17WTS and 17LER populations are identical. This result suggests that the
      difference in glucose transport between 17WTS and 17LER populations is not due to
      point mutations, but probably due to lower protein expression level. CONCLUSION:
      The BZ resistant population 17 LER presents a decrease in glucose uptake in
      response to drug pressure.

PMID- 22871259
TI  - Secreted human Ro52 autoantibody proteomes express a restricted set of public
      clonotypes.
AB  - Long-lived secreted autoantibody responses in systemic autoimmunity are generally
      regarded to be polyclonal and to express a diverse B-cell repertoire. Here, we
      have used a proteomic approach based on de novo sequencing to determine the
      clonality and V region structures of human autoantibodies directed against a
      prototypic systemic autoantigen, Ro52 (TRIM21). Remarkably, anti-Ro52
      autoantibodies from patients with primary Sjogren's syndrome, systemic lupus
      erythematosus, systemic sclerosis or polymyositis were restricted to two IgG1
      kappa clonotypes that migrated as a single species on isoelectric focusing;
      shared a common light chain paired with one of two closely-related heavy chains;
      and were public in unrelated patients. Targeted mass spectrometry using these
      uniquely mutated V region peptides as surrogates detected anti-Ro52
      autoantibodies in human sera with high sensitivity and specificity compared with
      traditional ELISA. Mass spectrometry-based detection of specific autoantibody
      motifs provides a powerful new tool for analysis of humoral autoimmunity.

PMID- 22871261
TI  - The chromosome 22q11.2 deletion: from the unification of biomedical fields to a
      new kind of genetic condition.
AB  - How can genetics reshape nosology? This paper examines the way knowledge about a
      genetic mutation - the microdeletion at chromosomal locus 22q11.2 - transformed
      our understanding of several rare clinical syndromes and designated a
      qualitatively new population of patients. Taking the 1400 papers about the
      22q11.2 deletion and the clinical conditions with which it was associated, we
      generate a network of papers tied by citations for each of the last 35 years.
      Using a modularity algorithm, we identify communities and evaluate their salience
      for the networks' overall structure. This analysis, supplemented by historical
      research and fieldwork with relevant experts and the advocates of affected
      children conducted during 2011-12, reveals that the 22q11.2 deletion acted as a
      'boundary object' that unified clinical literatures and led to the emergence of a
      new kind of medical condition: 22q11.2 Deletion Syndrome (DS). The case of
      22q11.2DS extends our understanding of 'genomic designation' - the delineation
      and diagnosis of clinically diffuse conditions according to characteristics of
      the genome - and demonstrates that observations from genetics can reconfigure
      existing categories of biomedical research and lead to the emergence of
      qualitatively new diagnostic categories.

PMID- 22871260
TI  - Magnetic-activated cell sorting of TCR-engineered T cells, using tCD34 as a gene
      marker, but not peptide-MHC multimers, results in significant numbers of
      functional CD4+ and CD8+ T cells.
AB  - T cell-sorting technologies with peptide-MHC multimers or antibodies against gene
      markers enable enrichment of antigen-specific T cells and are expected to enhance
      the therapeutic efficacy of clinical T cell therapy. However, a direct comparison
      between sorting reagents for their ability to enrich T cells is lacking. Here, we
      compared the in vitro properties of primary human T cells gene-engineered with
      gp100(280-288)/HLA-A2-specific T cell receptor-alphabeta (TCRalphabeta) on
      magnetic-activated cell sorting (MACS) with various peptide-MHC multimers or an
      antibody against truncated CD34 (tCD34). With respect to peptide-MHC multimers,
      we observed that Streptamer((r)), when compared with pentamers and tetramers,
      improved T cell yield as well as level and stability of enrichment, of TCR
      engineered T cells (>65% of peptide-MHC-binding T cells, stable for at least 6
      weeks). In agreement with these findings, Streptamer, the only detachable
      reagent, revealed significant T cell expansion in the first week after MACS.
      Sorting TCR and tCD34 gene-engineered T cells with CD34 monoclonal antibody (mAb)
      resulted in the most significant T cell yield and enrichment of T cells (>95% of
      tCD34 T cells, stable for at least 6 weeks). Notably, T cells sorted with CD34
      mAb, when compared with Streptamer, bound about 2- to 3-fold less peptide-MHC but
      showed superior antigen-specific upregulated expression of CD107a and production
      of interferon (IFN)-gamma. Multiparametric flow cytometry revealed that CD4(+) T
      cells, uniquely present in CD34 mAb-sorted T cells, contributed to enhanced IFN
      gamma production. Taken together, we postulate that CD34 mAb-based sorting of
      gene-marked T cells has benefits toward applications of T cell therapy,
      especially those that require CD4(+) T cells.

PMID- 22871262
TI  - Novel photoresponsive cross-linking oligodeoxyribonucleotides having a caged
      alpha-chloroaldehyde.
AB  - We have developed photoresponsive cross-linking oligodeoxyribonucleotides (ODNs)
      for sequence-selective interstrand covalent bond formation toward target
      nucleotides. A phosphoramidite derivative of alpha-chloroaldehyde whose carbonyl
      group was converted to a bis(2-nitrobenzyl)acetal group was prepared for the
      synthesis of photoresponsive alpha-chloroaldehyde (PCA)-conjugated ODN. The bis(2
      nitrobenzyl)acetal group of a PCA-thymidine conjugate was completely removed by
      UV irradiation at 365 nm (400 mW/cm(2)) for 1 min. Photo-cross-linking studies
      revealed that PCA-ODN selectively reacted with the target nucleotides having an
      adenine or a cytosine moiety at the frontal position of the alpha-chloroaldehyde
      group.

PMID- 22871263
TI  - Chronic serotonin-norepinephrine reuptake transporter inhibition modifies basal
      respiratory output in adult mouse in vitro and in vivo.
AB  - Respiratory disturbances are a common feature of panic disorder and present as
      breathing irregularity, hyperventilation, and increased sensitivity to carbon
      dioxide. Common therapeutic interventions, such as tricyclic (TCA) and selective
      serotonin reuptake inhibitor (SSRI) antidepressants, have been shown to
      ameliorate not only the psychological components of panic disorder but also the
      respiratory disturbances. These drugs are also prescribed for generalized anxiety
      and depressive disorders, neither of which are characterized by respiratory
      disturbances, and previous studies have demonstrated that TCAs and SSRIs exert
      effects on basal respiratory activity in animal models without panic disorder
      symptoms. Whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have
      similar effects on respiratory activity remains to be determined. Therefore, the
      current study was designed to investigate the effects of chronic administration
      of the SNRI antidepressant venlafaxine (VHCL) on basal respiratory output. For
      these experiments, we recorded phrenic nerve discharge in an in vitro arterially
      perfused adult mouse preparation and diaphragm electromyogram (EMG) activity in
      an in vivo urethane-anesthetized adult mouse preparation. We found that following
      28-d VHCL administration, basal respiratory burst frequency was markedly reduced
      due to an increase in expiratory duration (T(E)), and the inspiratory duty cycle
      (T(I)/T(tot)) was significantly shortened. In addition, post-inspiratory and
      spurious expiratory discharges were seen in vitro. Based on our observations, we
      suggest that drugs capable of simultaneously blocking both 5-HT and NE reuptake
      transporters have the potential to influence the respiratory control network in
      patients using SNRI therapy.

PMID- 22871264
TI  - A prospective study on association between 2 years change of waist circumference
      and incident hypertension in Han Chinese.
AB  - BACKGROUND: Few prospective studies on association between waist circumference
      and hypertension have taken account of the dynamic change of WC, which caused by
      lifestyle modification. METHODS: After a baseline investigation, we conducted the
      first and the second follow-up assessments for subjects after 2 and 5 years,
      respectively. The difference value (D-value, the value at the first follow-up
      minus the value at baseline) in WC was calculated to evaluate 2 years change of
      WC. The association between 2 years change of WC and incident hypertension was
      analyzed by using Cox proportional hazards regression model. RESULTS: Among 2778
      participants free of hypertension at baseline and the first follow-up, 660
      (23.8%) subjects developed hypertension over a period of 5 years (between the
      first and the second follow-up assessments). In both genders, the incidence
      density and HRs of hypertension were all increased with WC D-value regardless of
      their abdominal obesity status at baseline. Compared with participants who were
      non-abdominal obese both at baseline and first follow up, hypertension risk was
      higher in subjects who were abdominal obese both at baseline and the first follow
      up, and in subjects who were non-abdominal obese at baseline but with abdominal
      obesity at the first follow up. CONCLUSIONS: WC dynamic change was associated
      with incident hypertension, and more WC reduction was associated with more
      hypertension risk decrease.

PMID- 22871265
TI  - The effects of cyclic hydrostatic pressure on chondrogenesis and viability of
      human adipose- and bone marrow-derived mesenchymal stem cells in three
      dimensional agarose constructs.
AB  - This study investigates the effects of cyclic hydrostatic pressure (CHP) on
      chondrogenic differentiation of human adipose-derived stem cells (hASCs) in three
      dimensional (3-D) agarose constructs maintained in a complete growth medium
      without soluble chondrogenic inducing factors. hASCs were seeded in 2% agarose
      hydrogels and exposed to 7.5 MPa CHP for 4 h per day at a frequency of 1 Hz for
      up to 21 days. On days 0, 7, 14, and 21, the expression levels of collagen II,
      Sox9, aggrecan, and cartilage oligomeric matrix protein (COMP) were examined by
      real-time reverse transcriptase-polymerase chain reaction analysis. Gene
      expression analysis found collagen II mRNA expression in only the CHP-loaded
      construct at day 14 and at no other time during the study. CHP-loaded hASCs
      exhibited upregulated mRNA expression of Sox9, aggrecan, and COMP at day 7
      relative to unloaded controls, suggesting that CHP initiated chondrogenic
      differentiation of hASCs in a manner similar to human bone marrow-derived
      mesenchymal stem cells (hMSC). By day 14, however, loaded hASC constructs
      exhibited significantly lower mRNA expression of the chondrogenic markers than
      unloaded controls. Additionally, by day 21, the samples exhibited little
      measurable mRNA expression at all, suggesting a decreased viability. Histological
      analysis validated the lack of mRNA expression at day 21 for both the loaded and
      unloaded control samples with a visible decrease in the cell number and change in
      morphology. A comparative study with hASCs and hMSCs further examined long-term
      cell viability in 3-D agarose constructs of both cell types. Decreased cell
      metabolic activity was observed throughout the 21-day experimental period in both
      the CHP-loaded and control constructs of both hMSCs and hASCs, suggesting a
      decrease in cell metabolic activity, alluding to a decrease in cell viability.
      This suggests that a 2% agarose hydrogel may not optimally support hASC or hMSC
      viability in a complete growth medium in the absence of soluble chondrogenic
      inducing factors over long culture durations. This is the first study to examine
      the ability of mechanical stimuli alone, in the absence of chondrogenic factors
      transforming growth factor beta (TGF-beta)3, TGF-beta1 and/or bone morphogenetic
      protein 6 (BMP6) to induce hASC chondrogenic differentiation. The findings of
      this study suggest that CHP initiates hASC chondrogenic differentiation, even in
      the absence of soluble chondrogenic inductive factors, confirming the importance
      of considering both mechanical stimuli and appropriate 3-D culture for cartilage
      tissue engineering using hASCs.

PMID- 22871266
TI  - Association of body mass index, sagittal abdominal diameter and waist-hip ratio
      with cardiometabolic risk factors and adipocytokines in Arab children and
      adolescents.
AB  - BACKGROUND: Sagittal abdominal diameter (SAD) is a novel anthropometric measure
      hypothesized to be a surrogate measure of visceral abdominal obesity in adults.
      This study aims to determine whether SAD is superior to other anthropometric
      measures such as body mass index (BMI) and waist to hip ratio (WHR) in terms of
      association to cardiometabolic risk and circulating adipocytokine concentrations
      in a cohort of Saudi children and adolescents. METHODS: A total of 948 (495 boys
      and 453 girls) apparently healthy children with varying BMI, aged 10-17 years,
      were included in this cross sectional study. Fasting glucose, lipid profile,
      leptin, adiponectin, resistin, insulin, TNF-alpha and aPAI-1 were measured in
      serum and HOMA-IR was calculated. MetS components were defined according to the
      International Diabetes Federation (IDF) criteria. RESULTS: BMI was superior to
      SAD as well as WHR, and had the highest number of significant associations to
      MetS components and adipocytokines even after adjustment for age and gender,
      including blood pressure, lipids, glucose and leptin. CONCLUSION: In conclusion,
      while SAD is significantly associated with components of MetS among children and
      adolescents, it is not superior to BMI. The use of SAD therefore may not be
      practical for use in the pediatric clinical setting. Follow-up studies are needed
      to determine whether SAD has clinical significance in terms of harder outcomes
      such as predicting diabetes mellitus or cardiovascular diseases.

PMID- 22871267
TI  - Determination of the thrombin inhibitor AZD0837 and its metabolites in human bile
      using mixed mode solid phase extraction and LC-MS/MS.
AB  - A method for the determination of AZD0837 and its two metabolites AR-H069927 and
      AR-H067637 in human bile was developed and validated. All three analytes and
      their stable isotope-labeled internal standards were isolated from bile using
      solid phase extraction on a mixed mode reversed phase/anion exchange column.
      Elution was done at high ionic strength with 0.125 M ammoniumacetate in 50%
      methanol. The extraction recoveries were >75%. Due to the high concentration of
      AR-H067637 a portion of the extract was diluted before injection on to the LC
      column, while undiluted extract was directly injected for the analysis of AZD0837
      and AR-H069927. Chromatographic separation of all three analytes was achieved in
      a single system utilizing a C18 column based on fused core particle technology at
      high flow rate. The two metabolites were eluted when a gradient from 30 to 57%
      methanol was applied while the more hydrophobic pro-drug, AZD0837, eluted during
      a steeper second gradient from 57 to 80% methanol with the ammonium acetate
      concentration and acetic acid concentration kept constant at 3.8 mmol/L and 0.1%,
      respectively. The total cycle time was 3.2 min. Detection was performed using
      positive electrospray ionization tandem mass spectrometry. The linearity range
      was 0.02-20 MUmol/L for AZD0837 and AR-H069927, and 1-1000 MUmol/L for AR
      H067637. The repeatability and the overall precision were less than 15% (RSD) and
      the accuracy was within the interval 93-100%.

PMID- 22871268
TI  - L-aspartate effects on single neurons and interactions with glutamate in striatal
      slice preparation from chicken brain.
AB  - There is an accumulating evidence for a transmitter role of l-aspartate (l-Asp)
      in various brain regions. Recent studies from our laboratory have indicated that
      l-Asp is present in excitatory synapses of the striatum/nucl. accumbens of
      domestic chicks where it is co-released with l-glutamate (l-Glu) from axon
      terminals. Here we provide data on the postsynaptic effects of l-Asp alongside
      with l-Glu in striatal slices from chicken (1- to 10-day-old) using visually
      guided patch-clamp technique. l-Asp and l-Glu produced similar dose-dependent
      inward currents and an increase in spontaneous synaptic activity in all of the
      recorded striatal neurons. In the presence of TTX both the NMDA receptor
      antagonist D-AP5 and the AMPA/kainate receptor antagonist CNQX reduced and the co
      application of these two antagonists almost abolished the postsynaptic effects of
      l-Asp and l-Glu in a reversible manner. Testing the interactions of l-Asp and l
      Glu in these striatal neurons we found that co-application of l-Asp and l-Glut
      produced significantly larger inward currents than l-Asp or l-Glut alone. Our
      data are the first to demonstrate that l-Asp can induce postsynaptic effects on
      the chicken striatal neurons. These effects are mediated by both NMDA and non
      NMDA type ionotropic glutamate receptors and are similar to those evoked by l
      Glu. In addition our results show that co-application of l-Asp and l-Glut
      facilitates each other's effect, which is at least in part an excitatory amino
      acid (EAA) transporter dependent process. This phenomenon may explain the
      biological importance of the two EAAs with apparently similar postsynaptic
      activities in the same brain region.

PMID- 22871269
TI  - Reciprocal changes in input-output curves of motor evoked potentials while
      learning motor skills.
AB  - Reciprocal inhibition of antagonist muscles is crucial for motor skill learning
      in humans. However, the changes in reciprocal inhibition function during the
      motor learning process are unknown. The aim of this study was to systematically
      observe the changes in reciprocal inhibition function. We investigated the
      optimal coil position for simultaneously eliciting motor evoked potentials (MEPs)
      of reciprocal muscles, and the reciprocal changes in input-output (IO) curves
      during motor skill training. From ten healthy volunteers, the IO curves of MEPs
      were measured for the midpoint between the center of gravity (CoG) of the
      extensor carpi radialis (ECR) and the flexor carpi radialis (FCR) muscles, for
      the CoG of ECR, and for the FCR muscles using transcranial magnetic stimulation
      (TMS). In addition, the IO curves of the ECR and the FCR muscles were measured
      before and after the motor skill training of rapid wrist extension. The IO curves
      measured at the midpoint between the CoGs of the ECR and the FCR muscles and the
      CoG of each muscle were homogenous. However, after training to perform rapid
      wrist extension, the IO curve of the agonist (ECR) muscle was increased, while
      the antagonist (FCR) muscle was decreased. The present findings validate the IO
      curves simultaneously measured for reciprocal muscles, and suggest that motor
      skill training could induce reciprocal change in corticospinal excitability.

PMID- 22871270
TI  - Impaired response of hypoxic sensor protein HIF-1alpha and its downstream
      proteins in the spinal motor neurons of ALS model mice.
AB  - We have recently reported spinal blood flow-metabolism uncoupling in an
      amyotrophic lateral sclerosis (ALS) animal model using Cu/Zn-superoxide dismutase
      1 (SOD1)-transgenic (Tg) mice, suggesting a relative hypoxia in the spinal cord.
      However, the hypoxic stress sensor pathway has not been well studied in ALS.
      Here, we examined temporal and spatial changes of the hypoxic stress sensor
      proteins HIF-1alpha and its downstream proteins (VEGF, HO-1, and EPO) during the
      normoxiccourse of motor neuron (MN) degeneration in the spinal cord of these ALS
      model mice. We found that HIF-1alpha protein expression progressively increased
      both in the anterior large MNs and the surrounding glial cells in Tg mice from
      early symptomatic 14 week (W) and end stage 18 W. Double immunofluorescence
      analysis revealed that HIF-1alpha, plus GFAP and Iba-1 double-positive
      surrounding glial cells, progressively increased from 14 W to 18 W, although the
      immunohistochemistry in large MNs did not change. Expression levels of VEGF and
      HO-1 also showed a progressive increase but were significant only in the
      surrounding glial cells at 18 W. In contrast, EPO protein expression was
      decreased in the surrounding glial cells of Tg mice at 18 W. Because HIF1-alpha
      serves as an important mediator of the hypoxic response, these findings indicate
      that MNs lack the neuroprotective response to hypoxic stress through the HIF
      1alpha system, which could be an important mechanism of neurodegeneration in ALS.

PMID- 22871271
TI  - Influence of personal mobile phone ringing and usual intention to answer on
      driver error.
AB  - Given evidence of effects of mobile phone use on driving, and also legislation,
      many careful drivers refrain from answering their phones when driving. However,
      the distracting influence of a call on driving, even in the context of not
      answering, has not been examined. Furthermore, given that not answering may be
      contrary to an individual's normal habits, this study examined whether
      distraction caused by the ignored call varies according to normal intention to
      answer whilst driving. That is, determining whether the effect is more than a
      simple matter of noise distraction. Participants were 27 young drivers (18-29
      years), all regular mobile users. A Theory of Planned Behaviour questionnaire
      examined predictors of intention to refrain from answering calls whilst driving.
      Participants provided their mobile phone number and were instructed not to answer
      their phone if it were to ring during a driving simulation. The simulation
      scenario had seven hazards (e.g. car pulling out, pedestrian crossing) with three
      being immediately preceded by a call. Infractions (e.g. pedestrian collisions,
      vehicle collisions, speed exceedances) were significantly greater when distracted
      by call tones than with no distraction. Lower intention to ignore calls whilst
      driving correlated with a larger effect of distraction, as was feeling unable to
      control whether one answered whilst driving (Perceived Behavioural Control). The
      study suggests that even an ignored call can cause significantly increased
      infractions in simulator driving, with pedestrian collisions and speed
      exceedances being striking examples. Results are discussed in relation to
      cognitive demands of inhibiting normal behaviour and to drivers being advised to
      switch phones off whilst driving.

PMID- 22871272
TI  - The effects of cannabis and alcohol on simulated driving: Influences of dose and
      experience.
AB  - BACKGROUND: Cannabis and alcohol are the most popular drugs amongst recreational
      users, and most prevalent in injured and deceased drivers. Clarification of the
      interactive effects of these drugs upon driving behaviour is critical for
      reducing drug-related road deaths. OBJECTIVES: The current study had two
      objectives, to examine the effects of cannabis and alcohol on driving
      performance, and identify if any differences between the effects of cannabis and
      alcohol on driving performance exist between regular cannabis users and non
      regular cannabis users. METHODS: The project involved 80 participants (49 male,
      31 female) who were abstinent recreational users of alcohol and marijuana. They
      participated in six experimental sessions that involved the consumption of
      cannabis cigarettes containing no THC, 1.8% THC or 3% THC together with the
      consumption of alcohol to obtain either 0% BAC, 0.03% BAC or 0.05% BAC. The six
      sessions were double-blind, counter-balanced, placebo-controlled and medically
      supervised. Forty participants were allocated to the cannabis with low alcohol
      (0.03% BAC) group, and 40 participants were allocated to the cannabis with high
      alcohol (0.05% BAC) group. Driving simulator performance was assessed at 20min
      post-drug administration and blood samples were taken before and after driving.
      RESULTS: Driving simulator performance was more impaired in the THC and alcohol
      combined conditions. Consistent with past research, the level of THC detected in
      blood is higher when THC is consumed with alcohol, than when cannabis is consumed
      alone, and regular cannabis users returned higher levels of THC in plasma than
      non-regular users. Generally, regular cannabis users displayed more driving
      errors than non-regular cannabis users.

PMID- 22871273
TI  - Combined chirp coded tissue harmonic and fundamental ultrasound imaging for
      intravascular ultrasound: 20-60 MHz phantom and ex vivo results.
AB  - The application of chirp coded excitation to pulse inversion tissue harmonic
      imaging can increase signal to noise ratio. On the other hand, the elevation of
      range side lobe level, caused by leakages of the fundamental signal, has been
      problematic in mechanical scanners which are still the most prevalent in high
      frequency intravascular ultrasound imaging. Fundamental chirp coded excitation
      imaging can achieve range side lobe levels lower than -60dB with Hanning window,
      but it yields higher side lobes level than pulse inversion chirp coded tissue
      harmonic imaging (PI-CTHI). Therefore, in this paper a combined pulse inversion
      chirp coded tissue harmonic and fundamental imaging mode (CPI-CTHI) is proposed
      to retain the advantages of both chirp coded harmonic and fundamental imaging
      modes by demonstrating 20-60MHz phantom and ex vivo results. A simulation study
      shows that the range side lobe level of CPI-CTHI is 16dB lower than PI-CTHI,
      assuming that the transducer translates incident positions by 50MUm when two
      beamlines of pulse inversion pair are acquired. CPI-CTHI is implemented for a
      proto-typed intravascular ultrasound scanner capable of combined data acquisition
      in real-time. A wire phantom study shows that CPI-CTHI has a 12dB lower range
      side lobe level and a 7dB higher echo signal to noise ratio than PI-CTHI, while
      the lateral resolution and side lobe level are 50MUm finer and -3dB less than
      fundamental chirp coded excitation imaging respectively. Ex vivo scanning of a
      rabbit trachea demonstrates that CPI-CTHI is capable of visualizing blood vessels
      as small as 200MUm in diameter with 6dB better tissue contrast than either PI
      CTHI or fundamental chirp coded excitation imaging. These results clearly
      indicate that CPI-CTHI may enhance tissue contrast with less range side lobe
      level than PI-CTHI.

PMID- 22871274
TI  - Organic free radicals.

PMID- 22871275
TI  - Radicals and radical ions as intermediates of electron transfer processes through
      peptides.
AB  - Electron transfer (ET) through peptides and proteins is a key biochemical
      process, which involves radicals and radical ions as reactive intermediates. We
      have developed an assay that allows us to study this fundamental chemical
      reaction.

PMID- 22871276
TI  - Biomimetic models of radical stress and related biomarkers.
AB  - The biological consequences of free radical production is the central subject of
      a very lively scientific debate, focusing on the estimation of the type and
      extent of damage, as well as the efficiency of the protective and repair systems.
      When studying free radical based chemical mechanisms,  it is very important to
      establish biomimetic models, which allow the experiments to be performed in a
      simplified environment, but suitably designed to be in strict connection with
      cellular conditions. The biomimetic modeling approach has been coupled with
      physical organic chemistry methodologies  and knowledge of free radical
      reactivity. Molecular basis of important processes have been identified, building
      up molecular libraries of products concerning unsaturated lipids, sulfur
      containing proteins and nucleic acids, to be developed as biomarkers. Ongoing
      projects in our group deal  with lipidomics, genomics and proteomics of free
      radical stress and some examples will be described.

PMID- 22871277
TI  - Free radical-mediated hydroxymethylation using CO and HCHO.
AB  - Tin-free radical hydroxymethylations of haloalkanes using CO and HCHO as a C1
      unit proceed efficiently in the presence of borohydrides as radical mediators. In
      the approach using CO, the formation of aldehydes by radical carbonylation and
      their subsequent reduction by hydrides lead  to alcohols. On the other hand, the
      use of formaldehyde is more straightforward, in which the key reaction is alkyl
      radical addition to formaldehyde to give alkoxy radical, which abstracts hydrogen
      from borohydride reagents. The cascade sequences were observed in the reaction of
      cholesteryl  bromide with HCHO, which displays the diverse applications of HCHO
      in radical chemistry.

PMID- 22871278
TI  - Mn(III)-catalyzed radical reactions of 1,3-dicarbonyl compounds and
      cyclopropanols with vinyl azides for divergent synthesis of azaheterocycles.
AB  - Mn(III)-catalyzed formal [3+2]- and [3+3]-annulations have been developed using
      readily available vinyl azides with 1,3-dicarbonyl compounds and cyclopropanols.
      Vinyl azides were successfully applied as a three-atom unit including one
      nitrogen to prepare various azaheterocycles via Mn(III)-catalyzed radical
      reactions.

PMID- 22871279
TI  - NHC-boranes: air- and water-tolerant co-initiators for type II
      photopolymerizations.
AB  - N-Hetereocyclic carbene (NHC) complexes of boranes are stable compounds that can
      be used as co-initiators for the type II photopolymerization of acrylates. The
      present account summarizes this new development for polymerization and boron
      chemistry. In particular, NHC-boranes are air-  and water-tolerant, which
      enhances the practicality of the photopolymerizations.

PMID- 22871280
TI  - Ruthenium-catalyzed atom transfer radical addition reactions.
AB  - Certain ruthenium complexes are potent catalysts for atom transfer radical
      addition (ATRA) and cyclization (ATRC) reactions, in particular if they are used
      in conjunction with reducing agents such as magnesium. This short overview
      summarizes recent developments in this area with special  focus on contributions
      from our laboratory.

PMID- 22871281
TI  - Radical-mediated dimerization and oxidation reactions for the synthesis of
      complex alkaloids.
AB  - Concise and general strategies for radical-based dimerization of cyclotryptamine
      and cyclotryptophan derivatives in addition to radical-based oxidation of
      structurally complex diketopiperazines are discussed. The impact of these radical
      based chemistries on the rapid generation of molecular  complexity is highlighted
      using representative examples from recent complex homodimeric alkaloid total
      syntheses. Additionally, a new and general strategy for radical-based directed
      heterodimerization of cyclotryptamine substructures via solvent-caged
      unsymmetrical diazene fragmentation  is discussed.

PMID- 22871282
TI  - Radical carbon-carbon bond formations enabled by visible light active
      photocatalysts.
AB  - This mini-review highlights the Stephenson group's contribution to the field of
      photoredox catalysis with emphasis on carbon-carbon bond formation. The
      realization of photoredox mediated reductive dehalogenation initiated
      investigations toward both intra- and intermolecular coupling  reactions. These
      reactions commenced via visible light-mediated reduction of activated halogens to
      give carbon-centered radicals that were subsequently involved in carbon-carbon
      bond forming transformations. The developed protocols using Ru and Ir based
      polypyridyl complexes as  photoredox catalysts were further tuned to efficiently
      catalyze overall redox neutral atom transfer radical addition reactions. Most
      recently, a simplistic flow reactor technique has been utilized to affect a broad
      scope of photocatalytic transformations with significant enhancement in reaction 
      efficiency.

PMID- 22871283
TI  - Recent advances in the chemistry of SmI(2)-H(2)O.
AB  - Recent work from our laboratories has shown SmI(2)-H(2)O to be a versatile,
      readily-accessible and non-toxic reductant that is more powerful than SmI(2).
      This review describes the reduction of functional groups that were previously
      thought to lie beyond  the reach of SmI(2) and complexity-generating cyclisations
      and cyclisation cascades triggered by the reduction of the ester carbonyl group
      with SmI(2)-H(2)O.

PMID- 22871284
TI  - Some aspects of the radical chemistry of xanthates.
AB  - Xanthates and related thiocarbonylthio derivatives have proved to be exceedingly
      useful substrates for both inter- and intra- molecular radical additions. The
      intermolecular addition to unactivated alkenes, in particular, provides
      tremendous opportunities for synthesis: various functional  groups can be brought
      together under mild, neutral conditions. Since the adduct is also a xanthate,
      iteration allows the formation of block polymers through a controlled radical
      polymerisation (the RAFT/MADIX technology). Also of some importance is the access
      to highly substituted aromatic  and heteroaromatic derivatives.

PMID- 22871285
TI  - Transition-metal-free oxidative coupling reactions for the formation of C-C and C
      N bonds mediated by TEMPO and its derivatives.
AB  - The application of nitroxides for the development of new synthetic methods and
      their implementation in polymer chemistry, material science and beyond is one of
      the major research topics in our laboratory in the institute of organic chemistry
      at the WWU Munster. This short review  focuses on our recent progress towards
      nitroxide-based transition-metal-free oxidative coupling reactions. The demand
      for organic surrogates for transition metals in such transformations is in our
      eyes unquestionable, since environmental and economic issues have become
      progressively more important  in recent years. For this purpose, the 2,2,6,6
      tetramethylpiperidine-N-oxyl radical (TEMPO) is shown to be a highly efficient
      oxidant for the homo- and cross-coupling of Grignard reagents. This powerful C-C
      bond forming strategy allows the generation of conjugated polymers  from
      bifunctional Grignard reagents. Moreover, cross-coupling of alkynyl Grignard
      compounds and nitrones can be accomplished under aerobic atmosphere with
      catalytic amounts of TEMPO. It is also shown that TEMPO-derived N-oxoammonium
      salts can act as suitable oxidants for  formation of C-N bonds between non
      preactivated benzoxazoles and secondary amines under metal-free conditions.

PMID- 22871286
TI  - The development of organic super electron donors.
AB  - In the past decade, a host of exceptionally strong organic electron donors has
      been designed and prepared; their redox potentials are more negative than any
      previous neutral organic donors and extend beyond E(1/2) = -1 V vs. the saturated
      calomel electrode (SCE).  Their ability to reduce a wide range of organic
      functional groups has been demonstrated and this article provides an overview of
      the main advances in the area and the guiding principles for the design of these
      reagents.

PMID- 22871287
TI  - Homolytic reduction of onium salts.
AB  - Onium salts have proved to be efficient sources of carbon-centered radicals. They
      can undergo homolytic reduction by single electron transfer (SET) and participate
      in subsequent synthetic transformations. This review aims to provide an overview
      on the behavior of onium salts including  diazonium, sulfonium, selenonium,
      telluronium, phosphonium and iodonium cations toward various reductive methods
      such as radiolysis, electrolysis, photolysis or the use of SET reagents.
      Mechanistic and synthetic aspects are presented. Applications in polymers and
      materials science are not  covered.

PMID- 22871288
TI  - Reductive cleavage of 2,2,2-trichloroethyl esters by titanocene catalysis.
AB  - Esters are of widespread use for protecting carboxylic acids in organic
      synthesis. However, methods to cleave esters often employ harsh conditions.
      Herein, we report a new and mild method for the reductive cleavage of 2,2,2
      trichloroethylesters (TCE esters). Our radical method employs  Cp(2)TiCl as an
      electron transfer catalyst and Zn dust as stoichiometric reducing agent. It
      avoids the use of strong Bronstedt-acids as well as aqueous conditions and can be
      carried out at room temperature.

PMID- 22871289
TI  - Enzyme-triggered radical reactions: another approach for tin-free radical
      chemistry.
AB  - The system laccase/mediator/dioxygen is able to trigger radical reactions with
      radical precursors which are not natural substrates of this enzyme. The radical
      generation has been accomplished by single electron transfer oxidation of a 1,3
      dicarbonyl precursor. The process is exemplified  with a radical cascade.

PMID- 22871290
TI  - Photoredox catalysis for polymerization reactions.
AB  - Photoredox catalysis is now well-known in organic synthesis for the formation of
      free radicals under very soft irradiations conditions (e.g. sunlight, household
      fluorescence or LED bulbs, Xe lamp). This method has been introduced here to the
      polymer chemistry area to initiate  ring opening polymerizations (ROP) or free
      radical polymerizations (FRP). The present paper will give an up-to date
      situation of the photocatalyst achievements in FRP and ROP.

PMID- 22871292
TI  - On-line process control of the roast degree of coffee.

PMID- 22871293
TI  - Introducing a reversible linkage to block copolymer self-assembly: towards
      controlling nanopore chemistry.

PMID- 22871295
TI  - Intramuscular stimulation therapy for healthcare: a systematic review of
      randomised controlled trials.
AB  - OBJECTIVE: A systematic review of randomised controlled trials was conducted to
      evaluate the efficacy and effectiveness of intramuscular stimulation (IMS).
      METHODS: Electronic databases including Medline, EMBASE, PsycINFO, Cumulative
      Index to Nursing and Allied Health Literature, Allied and Complementary Medicine
      Database, the Cochrane Library, China National Knowledge Infrastructure,
      KoreaMED, Korean Studies Information Service System, RISS and DBPIA were searched
      through June, 2012. The Cochrane criteria were used to assess the risk of bias
      for the individual studies. RESULTS: A total of 416 publications were initially
      collected and four studies were included in this review. One study evaluated the
      efficacy of IMS for chronic tension-type headaches; IMS showed a better effect
      than the sham (headache index: mean difference (MD) -4.90, 95% CI -9.53 to 
      0.27). Three studies tested the effectiveness of IMS for various conditions. In
      the first study no significant difference was observed in a comparison of IMS and
      meloxicam therapy for chronic shoulder pain (pain-visual analogue scale (VAS): MD
      -0.05, 95% CI -0.25 to 0.16). The second study in patients with myofascial pain
      syndrome of the upper trapezius muscle found that IMS had a greater effect than
      simple dry needling measured by the pain-VAS (MD -2.70, 95% CI -3.77 to -1.63).
      In the third study, patients with lower back pain who received IMS plus the
      standard treatment had a better status at discharge than those receiving the
      standard treatment alone (relative risk 1.63, 95% CI 1.18 to 2.24). CONCLUSIONS:
      Despite the positive results of these individual studies, the level of evidence
      supporting the efficacy and effectiveness of IMS for several conditions remains
      insufficient because of concerns about a lack of precision and a high risk of
      bias of the included studies. Rigorous large-scale clinical trials of IMS are
      needed to evaluate the clinical utility of this technique.

PMID- 22871296
TI  - Unusual cold denaturation of a small protein domain.
AB  - A thermal unfolding study of the 45-residue alpha-helical domain UBA(2) using
      circular dichroism is presented. The protein is highly thermostable and exhibits
      a clear cold unfolding transition with the onset near 290 K without denaturant.
      Cold denaturation in proteins is rarely observed in general and is quite unique
      among small helical protein domains. The cold unfolding was further investigated
      in urea solutions, and a simple thermodynamic model was used to fit all thermal
      and urea unfolding data. The resulting thermodynamic parameters are compared to
      those of other small protein domains. Possible origins of the unusual cold
      unfolding of UBA(2) are discussed.

PMID- 22871297
TI  - Effects of the mutation of selected genes of cotton leaf curl Kokhran virus on
      infectivity, symptoms and the maintenance of cotton leaf curl Multan
      betasatellite.
AB  - Cotton leaf curl Kokhran virus (CLCuKoV) is a cotton-infecting monopartite
      begomovirus (family Geminiviridae). The effects of mutation of the coat protein
      (CP), V2, C2 and C4 genes of CLCuKoV on infectivity and symptoms in Nicotiana
      benthamiana were investigated. Each mutation introduced a premature stop codon
      which would lead to premature termination of translation of the gene. Mutation of
      the CP gene abolished infectivity. However, transient expression of the CLCuKoV
      CP gene under the control of the Cauliflower mosaic virus 35S promoter (35S
      Ko(CP)), at the point of inoculation, led to a small number of plants in which
      viral DNA could be detected by PCR in tissues distal to the inoculation site.
      Mutations of the V2, C2 and C4 genes reduced infectivity. The V2 and C2 mutants
      did not induce symptoms, whereas the C4 mutation was associated with attenuated
      symptoms. Infections of plants with the C4 mutant were associated with viral DNA
      levels equivalent to the wild-type virus, whereas viral DNA levels for the V2
      mutant were low, detectable by Southern blot hybridisation, and for the C2 mutant
      were detectable only by PCR. Significantly, transient expression of the CLCuKoV
      C2 gene at the point of inoculation, raised virus DNA levels in tissues distal to
      the inoculation site such that they could be detected by Southern hybridisation,
      although they remained at well below the levels seen for the wild-type virus, but
      reduced the infectivity of the virus. These findings are consistent with earlier
      mutation studies of monopartite begomoviruses and our present knowledge
      concerning the functions of the four genes suggesting that the CP is essential
      for long distance spread of the virus in plants, the C4 is involved in modulating
      symptoms, the C2 interferes with host defence and the V2 is involved in virus
      movement. The results also suggest that the V2, C2 and C4 may be pathogenicity
      determinants. Additionally the effects of the mutations of CLCuKoV genes on
      infections of the virus in the presence of its cognate betasatellite, Cotton leaf
      curl Multan betasatellite (CLCuMuB), were investigated. Mutation of the C4 gene
      had no effect on maintenance of the betasatellite, although the betasatellite
      enhanced symptoms. Inoculation of the C2 mutant with CLCuMuB raised the
      infectivity of the virus to near wild-type levels, although the numbers of plants
      in which the betasatellite was maintained was reduced, in comparison to wild-type
      virus infections with CLCuMuB, and viral DNA could not be detected by Southern
      hybridisation. Transient expression of the C2 gene at the point of inoculation
      raised virus DNA levels in tissues distal to the inoculation site but also
      reduced the infectivity of the virus and the numbers of plants in which the
      betasatellite was maintained. CLCuMuB restored the infectivity of the V2 mutant
      to wild-type levels but only in a small number of plants was the satellite
      maintained and infections were non-symptomatic. Although inoculation of the CP
      mutant with CLCuMuB did not restore infectivity, co-inoculation with 35S-Ko(CP)
      increased the number of plants in which the virus could be detected, in
      comparison to plants inoculated with the mutant and 35S-Ko(CP), and also resulted
      in two plants (out of 15 inoculated) in which the betasatellite could be detected
      by PCR. This indicates that the V2, C2 and almost certainly the CP are important
      for the maintenance of betasatellites by monopartite begomoviruses. The
      significance of these findings is discussed.

PMID- 22871298
TI  - Genetic diversity of Flavobacterium psychrophilum isolated from rainbow trout in
      France: predominance of a clonal complex.
AB  - Flavobacterium psychrophilum is the causative agent of "bacterial cold water
      disease" and "rainbow trout fry syndrome" in salmonid farming worldwide. These
      diseases, especially rainbow trout fry syndrome, are among the main hazards for
      French aquaculture. In this study, a multilocus sequence typing approach (MLST)
      was used to evaluate the genetic diversity of this bacterium. Seven housekeeping
      genes in a set of 66 isolates were investigated. They were recently collected
      from rainbow trout during clinical episodes in French farms from the two main
      geographical areas of production. A total of 5808 bp of sequence were analyzed
      for each isolate and showed relatively low levels of gene (H=0.4313) and
      nucleotide (pi*100=0.31%) diversities. MLST identified 15 sequence types (STs),
      of which 14 have never been described. eBURST analysis separated the 15 STs in
      one clonal complex of 8 genetically related STs (with ST2 as founder) and 7
      singletons. Genetic diversity was largely due to recombination, as demonstrated
      by a pairwise homoplasy index (PHI=5.35*10(-9)) significantly different from zero
      (p<0.05). The evolution of standardized association index (I(A)(S)) (all
      isolates: 0.6088, p<0.05; single representative of STs: 0.4567, p<0.05; and
      clusters of STs: 0.084, p>0.05), showed an epidemic structure of the population.
      These results emphasized the expansion of a limited number of dominant genetic
      variants in French clinical F. psychrophilum isolates from a single host species,
      with no geographic relationships.

PMID- 22871300
TI  - Relationship of angiographically defined coronary artery disease with insulin
      sensitivity and secretion in subjects with different glucose tolerance.
AB  - BACKGROUND: Most studies pay attention to the relationship between insulin
      resistance and coronary artery disease (CAD) in patients with abnormal glucose
      tolerance. But few studies have focused on the role of insulin secretion. The aim
      of this study was to investigate the association between insulin sensitivity,
      insulin secretion, and CAD in patients with different glucose metabolic status.
      METHODS: 316 newly diagnosed patients with different glucose metabolic status
      (according to the results of oral glucose tolerance test) were included in this
      study. The homeostasis model assessment of insulin resistance (HOMA(IR)) and
      Matsuda index were used to estimate insulin sensitivity; the insulin secretion
      was assessed using the HOMA-beta, insulinogenic index, area under the curve -
      insulin/glucose (AUC-Ins/Glu). CAD was defined as >=50% of luminal stenosis in at
      least one major coronary vessel through coronary angiography. RESULTS: Univariate
      analysis revealed that HOMA(IR) and Matsuda index were significantly different
      between the CAD group and the non-CAD group in all patients. Logistic analysis
      revealed that Matsuda index was an independent risk factor for the presence of
      CAD in all patients, and HOMA(IR) was an independent risk factor for the presence
      of CAD in normal glucose tolerance patients. Moreover, in the CAD group compared
      to the non-CAD group, there was no significant difference in the HOMA-beta,
      insulinogenic index, and AUC-Ins/Glu in all patients. CONCLUSIONS: Insulin
      resistance is closely related to the presence of CAD in newly diagnosed patients
      with different glucose metabolic status. The insulin secretion may not be closely
      related to the presence of CAD.

PMID- 22871301
TI  - Synthesis of 11C-labeled Kendine 91, a histone deacetylase inhibitor.
AB  - In the present paper, the synthesis of (11)C-labeled Kendine 91 (a HDAC inhibitor
      which has shown in vitro and in vivo activity in HCT 116 and MOLT 4 human cancer
      cell lines) is described for the first time. The radiosynthesis has been
      approached by reaction of the non-radioactive precursor 6-((3-(4-hydroxyphenyl)-5
      phenyl-1H-pyrrole-2-carboxamide))hexanehydroxamic acid with [(11)C]CH(3)I in
      basic media. Despite the presence of more than one reactive site in the chemical
      structure of the precursor, acceptable radiochemical yield (8.2+/-2.1%, decay
      corrected to the end of bombardment), specific activity (28.2+/-9.4 GBq/MUmol)
      and radiochemical purity values (>95%) were obtained in reasonably short
      preparation times (~40 min). Despite the moderate radiochemical yield, final
      radioactivity and radioactivity concentration values (1.8+/-0.3 GBq and 180
      MBq/ml, respectively) should be sufficient for putative in vivo studies in
      animals.

PMID- 22871302
TI  - Biodistribution and metabolism of 11C-labeled Kendine 91 in mice and rats.
AB  - The biodistribution pattern of [(11)C]Kendine 91 (a novel HDAC inhibitor) after
      IV administration has been evaluated using Positron Emission Tomography (rats)
      and gamma counting of dissected tissues (rats and mice) at different doses (1
      MUg/kg and 10.0 mg/kg). Metabolism in mice plasma has been also investigated by
      radio-HPLC. Obtained results (fast accumulation in lungs, heart, kidneys and
      liver; lower uptake in pancreas and muscle) are in concordance with previously
      reported results using HPLC/MS-MS. Plasma analysis studies showed a fast
      metabolism of the radiotracer.

PMID- 22871303
TI  - Negative attributions towards people with substance use disorders in South
      Africa: variation across substances and by gender.
AB  - BACKGROUND: Little research has examined attitudes towards people who use
      substances in low and middle income countries (LMIC). Therefore, the present
      study examined the attributions made by the general South African population
      about people who use substances and whether these attributions differ by the type
      of substance being used, the gender of the person using the substance, or the
      characteristics of the person making the attribution. METHOD: A convenience
      sample of 868 members of the general public was obtained through street-intercept
      methods. One of 8 vignettes portraying alcohol, cannabis, methamphetamine or
      heroin, with either a male or female as the protagonist was presented to each
      respondent. Respondents' attitudes towards the specific cases were investigated.
      RESULTS: Respondents held equally negative views of the presented substances,
      with the exception of the cannabis vignette which was considered significantly
      less "dangerous" than the alcohol vignette. Respondents were more likely to offer
      "help" to women who use alcohol, but more likely to suggest "coercion into
      treatment" for men. Individuals who scored higher on the ASSIST were more likely
      to hold negative attitudes towards substance users and black African respondents
      were more likely to offer help to individuals who use substances. CONCLUSION: The
      stigma associated with substance use in South Africa is high and not necessarily
      dependent on the drug of choice. However, a range of factors, including gender of
      the substance user, and ethnicity of the rater, may impact on stigma.
      Interventions designed to strengthen mental health literacy and gender-focused
      anti-stigma campaigns may have the potential to increase treatment seeking
      behaviour.

PMID- 22871304
TI  - Hydrogen sulfide prolongs postharvest shelf life of strawberry and plays an
      antioxidative role in fruits.
AB  - Accumulating evidence shows that hydrogen sulfide (H(2)S) plays various
      physiological roles in plants, such as seed germination, root organogenesis,
      abiotic stress tolerance, and senescence of cut flowers. However, whether H(2)S
      participates in the regulation of ripening and senescence in postharvest fruits
      remains unknown. In the present study, the effect of H(2)S on postharvest shelf
      life and antioxidant metabolism in strawberry fruits was investigated. Fumigation
      with H(2)S gas released from the H(2)S donor NaHS prolonged postharvest shelf
      life of strawberry fruits in a dose-dependent manner. Strawberry fruits fumigated
      with various concentrations of H(2)S sustained significantly lower rot index,
      higher fruit firmness, and kept lower respiration intensity and polygalacturonase
      activities than controls. Further investigation showed that H(2)S treatment
      maintained higher activities of catalase, guaiacol peroxidase, ascorbate
      peroxidase, and glutathione reductase and lower activities of lipoxygenase
      relative to untreated controls. H(2)S also reduced malondialdehyde, hydrogen
      peroxide, and superoxide anion to levels below control fruits during storage.
      Moreover, H(2)S treatment maintained higher contents of reducing sugars, soluble
      proteins, free amino acid, and endogenous H(2)S in fruits. We interpret these
      data as indicating that H(2)S plays an antioxidative role in prolonging
      postharvest shelf life of strawberry fruits.

PMID- 22871305
TI  - A multivariable assessment quantifying effects of cohort-level factors associated
      with combined mortality and culling risk in cohorts of U.S. commercial feedlot
      cattle.
AB  - Economic losses due to cattle mortality and culling have a substantial impact on
      the feedlot industry. Since criteria for culling may vary and may affect measures
      of cumulative mortality within cattle cohorts, it is important to assess both
      mortality and culling when evaluating cattle losses over time and among feedlots.
      To date, there are no published multivariable assessments of factors associated
      with combined mortality and culling risk. Our objective was to evaluate combined
      mortality and culling losses in feedlot cattle cohorts and quantify effects of
      commonly measured cohort-level risk factors (weight at feedlot arrival, gender,
      and month of feedlot arrival) using data routinely collected by commercial
      feedlots. We used retrospective data representing 8,904,965 animals in 54,416
      cohorts from 16 U.S. feedlots from 2000 to 2007. The sum of mortality and culling
      counts for each cohort (given the number of cattle at risk) was used to generate
      the outcome of interest, the cumulative incidence of combined mortality and
      culling. Associations between this outcome variable and cohort-level risk factors
      were evaluated using a mixed effects multivariable negative binomial regression
      model with random effects for feedlot, year, month and week of arrival. Mean
      arrival weight of the cohort, gender, and arrival month and a three-way
      interaction (and corresponding two-way interactions) among arrival weight, gender
      and month were significantly (P<0.05) associated with the outcome. Results showed
      that as the mean arrival weight of the cohort increased, mortality and culling
      risk decreased, but effects of arrival weight were modified both by the gender of
      the cohort and the month of feedlot arrival. There was a seasonal pattern in
      combined mortality and culling risk for light and middle-weight male and female
      cohorts, with a significantly (P<0.05) higher risk for cattle arriving at the
      feedlot in spring and summer (March-September) than in cattle arriving during
      fall, and winter months (November-February). Our results quantified effects of
      covariate patterns that have been heretofore difficult to fully evaluate in
      smaller scale studies; in addition, they illustrated the importance of utilizing
      multivariable approaches when quantifying risk factors in heterogeneous feedlot
      populations. Estimated effects from our model could be useful for managing
      financial risks associated with adverse health events based on data that are
      routinely available.

PMID- 22871306
TI  - Odontogenic infection leading to adult respiratory distress syndrome.

PMID- 22871307
TI  - Periosteal expansion before local bone reconstruction using a new technique for
      measuring soft tissue profile stability: a clinical study.
AB  - PURPOSE: To evaluate the outcome of intraoral soft tissue expansion by measuring
      the profile change using objective 3D metering equipment and to evaluate
      localized bone grafting after soft tissue expansion with regard to gain of bone
      and complications. MATERIALS AND METHODS: Using a prospective study design, we
      asked patients with an osseous and soft tissue defect on the buccal aspect of the
      alveolar process to participate in this study. In 10 patients (experimental
      group) a self-inflatable soft tissue expander was placed under the periosteum.
      After 2 weeks, the expander was removed and a particulated onlay bone graft was
      placed in the expanded area, protected by a titanium mesh covered with a collagen
      membrane. Ten patients (reference group) were treated with a mandibular ramus
      bone block graft. The soft tissue profile was registered before each surgical
      procedure. The vertical and lateral dimensions of the bone grafts were noted at
      the grafting procedure and at the implant installation. P < .05 was considered
      significant. RESULTS: The mean soft tissue profile change was 2.9 +/- 1.1 mm
      after soft tissue expansion and 2.3 +/- 2.1 mm at implant placement in the
      experimental group compared with 1.5 +/- 1.4 mm at implant placement in the
      reference group (P = .065). Two patients had minor perforations of the soft
      tissue expander. In the experimental group, the mean lateral bone augmentation
      after soft tissue expansion was 4.5 +/- 1.3 mm, and after healing, it decreased
      to 3.9 +/- 1.4 mm (P = .063). The mean vertical augmentation was 4.1 +/- 1.7 mm
      and had decreased at implant placement to 3.0 +/- 1.4 mm (P = .041). In the
      reference group, the mean lateral augmentation was 3.8 +/- 0.8 mm, and after
      healing, it reduced to 2.7 +/- 0.8 mm (P = .024). The mean vertical augmentation
      was 2.9 +/- 0.9 mm, and after healing of the bone graft at implant placement, it
      was reduced to 1.6 +/- 0.8 mm (P = .01). When smokers were excluded, there was
      significantly less resorption of the bone grafts in both lateral (P = .049) and
      vertical (P = .012) dimensions in the experimental group compared with the
      reference group. CONCLUSION: Hydrogel expansion of the periosteum is an
      applicable method to achieve a surplus of soft tissue to cover bone grafts. More
      refinements to the technique may be required to minimize complications,
      especially in smoking patients.

PMID- 22871308
TI  - Bilateral coronoid process hyperplasia with pseudocartilaginous joint formation:
      Jacob disease.

PMID- 22871309
TI  - Chief resident case experience and autonomy are associated with resident
      confidence and future practice plans.
AB  - PURPOSE: To measure oral and maxillofacial surgery (OMS) chief resident case
      experience, including autonomy, and discover the role of this experience in
      developing resident confidence and determining the scope of practice on
      completion of training. MATERIALS AND METHODS: A cross-sectional study was
      conducted using an online questionnaire made available to residents near the
      completion of their final year of training in United States OMS training
      programs. Predictors were the case numbers and autonomy level. Outcomes were the
      anticipated frequency of practice, confidence to meet the standard of care, and
      changes in anticipated practice scope. Each was measured in 10 domains within the
      scope of OMS. RESULTS: Eighty-four residents (44%) completed the 116-item
      questionnaire. All respondents were "very confident" in their ability to meet the
      standard of care in mandibular trauma and dentoalveolar surgery. Autonomy was
      associated with the confidence to meet the standard of care in midface trauma,
      temporomandibular joint, orthognathic, cosmetic, pathology, reconstructive, and
      craniofacial surgery. Associations were noted between primary surgeon cases and
      confidence in midface trauma, temporomandibular joint, orthognathic, cosmetic,
      and craniofacial surgery. Case numbers were associated with an anticipated
      frequency of practice within the domains of midface trauma, temporomandibular
      joint, cosmetic, and pathology surgery. CONCLUSIONS: Results of this study
      suggest an association between a resident's surgical case experience (overall
      exposure and autonomy) and that resident's future plans for practice and
      confidence to meet the standard of care in this specialty. OMS training curricula
      should evolve to incorporate an evaluation of competence and an appropriate
      transfer of responsibility and experience to residents, thus maximizing
      confidence and future practice opportunities.

PMID- 22871310
TI  - Sustained topical delivery of insulin from fibrin gel loaded with poly(lactic-co
      glycolic Acid) microspheres improves the biomechanical retention of titanium
      implants in type 1 diabetic rats.
AB  - PURPOSE: The aim of this study was to determine whether local insulin delivery
      using a fibrin gel (FG) loaded with insulin/poly(lactic-co-glycolic acid)
      microspheres (FGIPM) improves the biomechanical retention of titanium implants in
      type 1 diabetic rats. MATERIALS AND METHODS: Rats were divided randomly into 8
      groups: a group of healthy rats (no treatment), a group of diabetic rats (no
      treatment), and 6 groups of diabetic rats treated locally using carriers
      containing or not containing insulin. Rats received implants in the tibia and
      were allowed to heal for 4 or 8 weeks. Removal torque tests (RTQ) were performed
      to evaluate the biomechanical retention of the implants. RESULTS: In the diabetic
      control group, the mean RTQ values were significantly decreased compared with
      those for the healthy group. The local application of FGIPM increased the RTQ
      values in diabetic rats to the values found in the healthy rats at 8 weeks. The
      FG-treated group presented statistically significant higher mean RTQ values than
      the diabetic rats receiving no treatment. CONCLUSIONS: Local insulin delivery
      using FGIPM ameliorated the biomechanical retention of titanium implants in type
      1 diabetic rats and the FG had a beneficial effect.

PMID- 22871311
TI  - Malignant peripheral nerve sheath tumor of the oral cavity.

PMID- 22871312
TI  - Customized repair of fractured mandibular reconstruction plates.
AB  - PURPOSE: To describe a novel technique using custom prostheses to repair
      fractured mandibular reconstruction plates spanning discontinuity defects.
      MATERIALS AND METHODS: This is a retrospective case series reviewing the design,
      rapid manufacture, and use of a novel method to repair fractured plates. Three
      patients who could not undergo autogenous bone grafting procedures or replacement
      of the entire plate for medical or socioeconomic factors were treated by this
      method. RESULTS: Three patients with fractured reconstruction plates were treated
      with a custom prosthesis engaging the reconstruction plate. Continuity and
      function were restored with a minimally invasive operation and short hospital
      stay. The custom prosthesis remained in place with stable occlusion in all 3
      patients at a minimum of 9 months' follow-up. CONCLUSIONS: A technique using a
      custom prosthesis to quickly and less invasively restore continuity and function
      of the mandible after fracture of a reconstruction plate is described.

PMID- 22871313
TI  - The impact of traumatic events on emergency room nurses: findings from a
      questionnaire survey.
AB  - BACKGROUND: Emergency Nurses are routinely confronted with work related traumatic
      events and hectic work conditions. Several studies report a high prevalence of
      post-traumatic stress disorder (PTSD) in these nurses. Coping and social support
      seem to play an important role in the development of PTSD. OBJECTIVES: This study
      examines (1) the frequency of exposure to and the nature of traumatic events in
      Emergency Nurses, (2) the percentage of nurses that report symptoms of PTSD,
      anxiety, depression, somatic complaints and fatigue at a sub-clinical level, and
      (3) the contribution of traumatic events, coping and social support to PTSD
      symptoms, psychological distress, somatic complaints, fatigue and sleep
      disturbances. DESIGN: Cross-sectional data from 248 Emergency Nurses, from 15
      Flemish (Belgian) general hospitals, were analyzed. RESULTS: Emergency Nurses
      were found to be confronted frequently with work related traumatic events. Death
      or serious injury of a child/adolescent was perceived as the most traumatizing
      event. Almost one out of three nurses met sub-clinical levels of anxiety,
      depression and somatic complaints and 8.5% met clinical levels of PTSD. Levels of
      fatigue were high but not directly related to the frequency of exposure to
      traumatic events. Emotional coping was related to an increase in all outcomes;
      avoidant coping was related to more somatic complaints; problem focused coping
      was related to a decrease in psychological distress and perceived fatigue. Social
      support from colleagues and supervisor (head nurse) was found to have a
      protective effect on the occurrence of PTSD symptoms. CONCLUSION: Emergency
      Nurses are especially vulnerable to post-traumatic stress reactions due to
      repetitive exposure to work related traumatic incidents. This not only personally
      affects the nurses, but can also impact quality of care. Hospital management
      should act on the findings of this study and invest in supportive, communicative,
      empathic and anticipatory leadership, and provide time-out facilities, cognitive
      behavioral interventions and psychological counseling for Emergency Nurses on
      demand.

PMID- 22871314
TI  - Analysis of Babesia bovis infection-induced gene expression changes in larvae
      from the cattle tick, Rhipicephalus (Boophilus) microplus.
AB  - BACKGROUND: Cattle babesiosis is a tick-borne disease of cattle that has severe
      economic impact on cattle producers throughout the world's tropical and
      subtropical countries. The most severe form of the disease is caused by the
      apicomplexan, Babesia bovis, and transmitted to cattle through the bite of
      infected cattle ticks of the genus Rhipicephalus, with the most prevalent species
      being Rhipicephalus (Boophilus) microplus. We studied the reaction of the R.
      microplus larval transcriptome in response to infection by B. bovis. METHODS:
      Total RNA was isolated for both uninfected and Babesia bovis-infected larval
      samples. Subtracted libraries were prepared by subtracting the B. bovis-infected
      material with the uninfected material, thus enriching for expressed genes in the
      B. bovis-infected sample. Expressed sequence tags from the subtracted library
      were generated, assembled, and sequenced. To complement the subtracted library
      method, differential transcript expression between samples was also measured
      using custom high-density microarrays. The microarray probes were fabricated
      using oligonucleotides derived from the Bmi Gene Index database (Version 2).
      Array results were verified for three target genes by real-time PCR. RESULTS:
      Ticks were allowed to feed on a B. bovis-infected splenectomized calf and on an
      uninfected control calf. RNA was purified in duplicate from whole larvae and
      subtracted cDNA libraries were synthesized from Babesia-infected larval RNA,
      subtracting with the corresponding uninfected larval RNA. One thousand ESTs were
      sequenced from the larval library and the transcripts were annotated. We used a
      R. microplus microarray designed from a R. microplus gene index, BmiGI Version 2,
      to look for changes in gene expression that were associated with infection of R.
      microplus larvae. We found 24 transcripts were expressed at a statistically
      significant higher level in ticks feeding upon a B. bovis-infected calf
      contrasted to ticks feeding on an uninfected calf. Six transcripts were expressed
      at a statistically significant lower level in ticks feeding upon a B. bovis
      infected calf contrasted to ticks feeding on an uninfected calf. CONCLUSION: Our
      experimental approaches yielded specific differential gene expression associated
      with the infection of R. microplus by B. bovis. Overall, an unexpectedly low
      number of transcripts were found to be differentially expressed in response to B.
      bovis infection. Although the BmiGI Version 2 gene index
      (http://compbio.dfci.harvard.edu/tgi/cgi-bin/tgi/gimain.pl?gudb=b_microplus) was
      a useful database to help assign putative function to some transcripts, a
      majority of the differentially expressed transcripts did not have annotation that
      was useful for assignment of function and specialized bioinformatic approaches
      were necessary to increase the information from these transcriptome experiments.

PMID- 22871315
TI  - Modelling the spine as a deformable body: Feasibility of reconstruction using an
      optoelectronic system.
AB  - The aims of this study were to develop a kinematic model of the spine, seen as a
      continuous deformable body and to identify the smallest set of surface markers
      allowing adequate measurements of spine motion. The spine is widely considered as
      a rigid body or as a kinematic chain made up of a smaller number of segments,
      thereby introducing an approximation. It would be useful to have at our disposal
      a technique ensuring accurate and repeatable measurement of the shape of the
      whole spine. Ten healthy subjects underwent a whole-spine radiographic assessment
      and, simultaneously, an optoelectronic recording. Polynomial interpolations of
      the vertebral centroids, of the whole set of markers were performed. The
      similarity of the resulting curves was assessed. Our findings indicate that spine
      shape can be reproduced by 5th order polynomial interpolation. The best
      approximating curves are obtained from either 10- or 9-marker sets. Sagittal
      angles are systematically underestimated.

PMID- 22871317
TI  - Plant viruses in aqueous environment - survival, water mediated transmission and
      detection.
AB  - The presence of plant viruses outside their plant host or insect vectors has not
      been studied intensively. This is due, in part, to the lack of effective
      detection methods that would enable their detection in difficult matrixes and in
      low titres, and support the search for unknown viruses. Recently, new and
      sensitive methods for detecting viruses have resulted in a deeper insight into
      plant virus movement through, and transmission between, plants. In this review,
      we have focused on plant viruses found in environmental waters and their
      detection. Infectious plant pathogenic viruses from at least 7 different genera
      have been found in aqueous environment. The majority of the plant pathogenic
      viruses so far recovered from environmental waters are very stable, they can
      infect plants via the roots without the aid of a vector and often have a wide
      host range. The release of such viruses from plants can lead to their
      dissemination in streams, lakes, and rivers, thereby ensuring the long-distance
      spread of viruses that otherwise, under natural conditions, would remain
      restricted to limited areas. The possible sources and survival of plant viruses
      in waters are therefore discussed. Due to the widespread use of hydroponic
      systems and intensive irrigation in horticulture, the review is focused on the
      possibility and importance of spreading viral infection by water, together with
      measures for preventing the spread of viruses. The development of new methods for
      detecting multiple plant viruses at the same time, like microarrays or new
      generation sequencing, will facilitate the monitoring of environmental waters and
      waters used for irrigation and in hydroponic systems. It is reasonable to expect
      that the list of plant viruses found in waters will thereby be expanded
      considerably. This will emphasize the need for further studies to determine the
      biological significance of water-mediated transport.

PMID- 22871316
TI  - Regional differences in stem cell/progenitor cell populations from the mouse
      achilles tendon.
AB  - Specific niches may affect how cells from different regions contribute to tendon
      biology, particularly in regard to the healing of certain tendinopathies. The
      objectives of this study are to determine whether distinct subpopulations of
      stem/progenitor cells are found within the tendon proper and the epi- and
      paratenon, the peritenon, as well as to characterize these stem/progenitor cell
      populations. In this study, we hypothesized that tendon stem/progenitor cells
      exist in each region, that these populations possess distinct features, and that
      these populations while multipotent could have differing potentials. To test this
      hypothesis, stem/progenitor cells were isolated and characterized from the
      peritenon and tendon proper of mouse Achilles tendons. Colony-forming unit and
      multipotency assays, as well as flow cytometry, and real-time quantitative
      polymerase chain reaction analyses of stem cell markers were performed.
      Significantly, more stem/progenitor cell colonies were observed from cells
      derived from the tendon proper relative to the peritenon. Analysis of surface
      markers for stem/progenitor cells from both regions indicated that they were
      Sca1(+) (stem cell marker), Cd90(+) and Cd44(+) (fibroblast markers), Cd18(-)
      (leukocyte marker), Cd34(-) (hematopoietic and vascular marker), and Cd133(-)
      (perivascular marker). Tendon proper stem/progenitor cells had increased
      expression levels for tenomodulin (Tnmd) and scleraxis (Scx), indicative of
      enrichment of stem/progenitor cells of a tendon origin. In contrast, cells of the
      peritenon demonstrated relative increases in the vascular (endomucin) and
      pericyte (Cd133) markers relative to cells from the tendon proper.
      Stem/progenitor cells from both regions were multipotent (adipogenic,
      chondrogenic, osteogenic, and tenogenic). These findings demonstrated that
      different progenitor populations exist within discrete niches of the Achilles
      tendon-tendon proper versus peritenon. Overall, these data support the hypothesis
      that the progenitor pools from both regions have distinct properties and contain
      enriched progenitor subpopulations of different origins. Moreover, in considering
      their roles in tendon healing more broadly, they are potential cell sources that
      may differentially contribute to intrinsic and extrinsic tendon repair
      mechanisms. That is, intrinsic repair may require a progenitor class with
      predominant tendon marker expression, while extrinsic repair may involve a
      progenitor class recruited from perivascular cells of the peritenon.

PMID- 22871318
TI  - Removal of trace organic chemicals in onsite wastewater soil treatment units: a
      laboratory experiment.
AB  - Onsite wastewater treatment is used by 20% of residences in the United States.
      The ability of these systems, specifically soil treatment units (STUs), to
      attenuate trace organic chemicals (TOrCs) is not well understood. TOrCs released
      by STUs pose a potential risk to downstream groundwater and hydraulically
      connected surface water that may be used as a drinking water source. A series of
      bench-scale experiments were conducted using sand columns to represent STUs and
      to evaluate the efficacy of TOrC attenuation as a function of hydraulic loading
      rate (1, 4, 8, 12, and 30 cm/day). Each hydraulic loading rate was examined using
      triplicate experimental columns. Columns were initially seeded with raw
      wastewater to establish a microbial community, after which they were fed with
      synthetic wastewater and spiked with 17 TOrCs, in four equal doses per day, to
      provide a consistent influent water quality. After an initial start-up phase,
      effluent from all columns consistently demonstrated >90% reductions in dissolved
      organic carbon and nearly complete (>85%) oxidation of ammonia to nitrate,
      comparable to the performance of field STUs. The results of this study suggest
      STUs are capable of attenuating many TOrCs present in domestic wastewater, but
      attenuation is compound-specific. A subset of TOrCs exhibited an inverse
      relationship with hydraulic loading rate and attenuation efficiency. Atenolol,
      cimetidine, and TCPP were more effectively attenuated over time in each
      experiment, suggesting that the microbial community evolved to a stage where
      these TOrCs were more effectively biotransformed. Aerobic conditions as compared
      to anaerobic conditions resulted in more efficient attenuation of acetaminophen
      and cimetidine.

PMID- 22871319
TI  - Characterisation of organic matter in IX and PACl treated wastewater in relation
      to the fouling of a hydrophobic polypropylene membrane.
AB  - Extensive organic characterisation of a wastewater using liquid chromatography
      with a photodiode array and fluorescence spectroscopy (Method A), and UV(254) and
      organic carbon detector (Method B) was undertaken, as well as with fluorescence
      excitation emission spectroscopy (EEM). Characterisation was performed on the
      wastewater before and after ion exchange (IX) treatment and polyaluminium
      chlorohydrate (PACl) coagulation, and following microfiltration of the wastewater
      and pre-treated wastewaters. Characterisation by EEM was unable to detect
      biopolymers within the humic rich wastewaters and was not subsequently used to
      characterise the MF permeates. IX treatment preferentially removed low molecular
      weight (MW) organic acids and neutrals, and moderate amounts of biopolymers in
      contrast to a previous report of no biopolymer removal with IX. PACl
      preferentially removed moderate MW humic and fulvic acids, and large amounts of
      biopolymers. PACl showed a great preference for removal of proteins from the
      biopolymer component in comparison to IX. An increase in the fluorescence
      response of tryptophan-like compounds in the biopolymer fraction following IX
      treatment suggests that low MW neutrals may influence the structure and/or
      inhibit aggregation of organic compounds. Fouling rates for IX and PACl treated
      wastewaters had high initial fouling rates that reduced to lower fouling rates
      with time, while the untreated Eastern Treatment Plant (ETP) wastewater displayed
      a consistent, high rate of fouling. The results for the IX and PACl treated
      wastewaters were consistent with the long-term fouling rate being determined by
      cake filtration while both pore constriction and cake filtration contributed to
      the higher initial fouling rates. Higher rejection of biopolymers was observed
      for PACl and IX waters compared to the untreated ETP water, suggesting increased
      adhesion of biopolymers to the membrane or cake layer may lead to the higher
      rejection.

PMID- 22871321
TI  - Empirical use of fluoroquinolones for chest infections may mask tuberculosis and
      jeopardise chances of survival.

PMID- 22871320
TI  - Genotoxic stress modulates CDC25C phosphatase alternative splicing in human
      breast cancer cell lines.
AB  - CDC25 (cell division cycle 25) phosphatases are essential for cell cycle control
      under normal conditions and in response to DNA damage. They are represented by
      three isoforms, CDC25A, B and C, each of them being submitted to an alternative
      splicing mechanism. Alternative splicing of many genes is affected in response to
      genotoxic stress, but the impact of such a stress on CDC25 splicing has never
      been investigated. In this study, we demonstrate that genotoxic agents
      (doxorubicin, camptothecin, etoposide and cisplatin), alter the balance between
      CDC25C splice variants in human breast cancer cell lines both at the mRNA and
      protein levels. This modulation occurs during the response to moderate, sub
      lethal DNA damage. Our results also suggest that the CDC25C splice variants
      expression shift induced by a genotoxic stress is dependent on the ATM/ATR
      signaling but not on p53. This study highlights the modulation of CDC25C
      alternative splicing as an additional regulatory event involved in cellular
      response to DNA damage in breast cancer cells.

PMID- 22871322
TI  - Finding tuberculosis at the first encounter with HIV care: don't miss the
      opportunity to save a life.

PMID- 22871323
TI  - New solutions in service design and delivery are necessary to combat disease
      burden.

PMID- 22871324
TI  - Enabling biomarkers for tuberculosis control.
AB  - Accelerated control of tuberculosis (TB) requires better control measures.
      Biomarkers, which reliably diagnose active TB or even predict risk of disease
      progression in individuals, could facilitate rapid diagnosis and treatment of TB
      patients and allow preventive measures for latently  infected individuals with a
      high risk of TB. Moreover, biomarkers could speed up clinical trials with novel
      drug and vaccine candidates. Three platforms of global biomarker profiling will
      be described, with an emphasis on the most recent achievements: transcriptomics,
      proteomics and metabolomics.  Moreover, we will discuss the need for
      computational analyses to make the best use of the plethora of data generated by
      biomarker research. Aside from their potential prognostic and diagnostic value,
      biomarkers could provide deeper insight into pathological processes underlying
      disease, and  hence form the basis for novel intervention measures that target
      host molecules and pathways. We propose that biosignatures, which discriminate
      active TB from both latent infection and uninfected status, as well as from other
      diseases, will become available within the next decade. However,  simple, low
      cost biomarker-based point-of-care diagnosis will probably not be achieved in the
      next few years.

PMID- 22871325
TI  - Adverse respiratory effects of outdoor air pollution in the elderly.
AB  - Compared to the rest of the population, the elderly are potentially highly
      susceptible to the effects of outdoor air pollution due to normal and
      pathological ageing. The purpose of the present review was to gather data on the
      effects on respiratory health of outdoor air pollution in  the elderly, on whom
      data are scarce. These show statistically significant short-term and chronic
      adverse effects of various outdoor air pollutants on cardiopulmonary morbidity
      and mortality in the elderly. When exposed to air pollution, the elderly
      experience more hospital admissions for  asthma and chronic obstructive pulmonary
      disease (COPD) and higher COPD mortality than others. Previous studies also
      indicate that research on the health effects of air pollution in the elderly has
      been affected by methodological problems in terms of exposure and health effect
      assessments.  Few pollutants have been considered, and exposure assessment has
      been based mostly on background air pollution and more rarely on objective
      measurements and modelling. Significant progress needs to be made through the
      development of 'hybrid' models utilising the strengths of information  on
      exposure in various environments to several air pollutants, coupled with daily
      activity exposure patterns. Investigations of chronic effects of air pollution
      and of multi-pollutant mixtures are needed to better understand the role of air
      pollution in the elderly. Lastly, smoking, occupation,  comorbidities, treatment
      and the neighbourhood context should be considered as confounders or modifiers of
      such a role. In this context, the underlying biological, physiological and
      toxicological mechanisms need to be explored to better understand the phenomenon
      through a multidisciplinary  approach.

PMID- 22871326
TI  - Mortality among tuberculosis patients in the Democratic Republic of Congo.
AB  - SETTING: Kinshasa, Democratic Republic of Congo. OBJECTIVE: To identify
      programmatic interventions for improved survival in patients receiving treatment
      for tuberculosis (TB) at primary care clinics. DESIGN: Retrospective cohort of
      adult patients initiating anti-tuberculosis treatment  between January 2006 and
      May 2007. RESULTS: Among 5685 patients, 390 deaths occurred during anti
      tuberculosis treatment, of which half (52%) did so during the first 2 months.
      Patients with smear-negative pulmonary TB were at greater risk of death in the
      first 2 months of treatment (human  immunodeficiency virus [HIV] positive HR
      1.49, 95%CI 0.89-2.49; HIV-negative HR 1.77 95%CI 1.06-2.95), but not thereafter.
      Patients with extra-pulmonary TB were at increased risk of death in the first 2
      months of anti-tuberculosis treatment if they were non-HIV-infected (HR 2.42, 
      95%CI 1.52-3.85), and were half as likely to die during the remainder of
      treatment (HIV-positive HR 0.46, 95%CI 0.22-0.97; HIV-negative HR 0.47, 95%CI
      0.23-0.94). Antiretroviral therapy (ART) reduced the risk of death by an
      estimated 36% (HR 0.64, 95%CI 0.37-1.11). CONCLUSION: High mortality in the first
      months of anti-tuberculosis treatment could be reduced by addressing diagnostic
      delays, particularly for extra-pulmonary and smear-negative TB cases and, in HIV
      infected patients, by initiation of ART soon after starting anti-tuberculosis
      treatment.

PMID- 22871327
TI  - Indian study on epidemiology of asthma, respiratory symptoms and chronic
      bronchitis in adults (INSEARCH).
AB  - SETTING: Field sites in 12 districts in different parts of India. OBJECTIVE: To
      determine the nationwide population prevalence of and risk factors for asthma and
      chronic bronchitis (CB) in adults. DESIGN: A standardised validated questionnaire
      based on the International Union Against Tuberculosis and Lung Disease's 1984
      questionnaire was used to assess asthma and CB prevalence. Multivariate logistic
      regression analyses were performed to determine the risk factor associations.
      Estimates standardised to the 2011 population projection estimates for India were
      used to calculate the national disease burden. RESULTS: A total of 85,105 men and
      84,470 women from 12 urban and 11 rural sites were interviewed. One or more
      respiratory symptoms were present in 8.5% of individuals. The overall prevalence
      of asthma and CB was respectively 2.05% (adults aged >=15 years) and 3.49%
      (adults aged >=35 years). Advancing age, smoking, household environmental tobacco
      smoke exposure, asthma in a first-degree relative, and use of unclean cooking
      fuels were associated with increased odds of asthma and CB. The national burden
      of asthma and CB was estimated at respectively 17.23 and 14.84 million.
      CONCLUSION: Asthma and CB in adults pose an enormous health care burden in India.
      Most of the associated risk factors are preventable.

PMID- 22871328
TI  - Drug-induced hypothyroidism in patients receiving treatment for multidrug
      resistant tuberculosis in the UK.

PMID- 22871329
TI  - Interferon stimulated gene 15 (ISG15): molecular characterization and expression
      profile in endometrium of buffalo (Bubalus bubalis).
AB  - Interferon stimulated gene 15 (ISG15), one of the several proteins induced by
      conceptus derived Type I and/or a Type II interferon (IFN), is implicated as an
      important factor in determining the uterine receptivity and conceptus
      development. However, presence as well as specific role of the ISG15 in buffalo
      (Bubalus bubalis) reproduction is yet to be elucidated. In the present study,
      both genomic and cDNA sequences of bubaline (bu) ISG15 were cloned and
      investigated for its expression in different tissues of female reproductive tract
      of buffalo. Sequence analysis revealed 100% identity among the genomic sequences
      (1014 bp) of buISG15 from three different breeds of buffalo (viz., Murrah: Acc.
      No. DQ118137, Mehsana: Acc. No. DQ118138, and Nagpuri: Acc. No. DQ118136) and
      cDNAs (Acc. Nos. HM543268-HM543270). As in cattle, the buISG15 was comprised of
      two exons of 57 bp and 520 bp encoding a peptide of 154 amino acids. Moreover,
      the buISG15 cDNA sequence exhibited 98.3% and 98.5% identity with that of taurine
      and indicine cattle, respectively. Subsequent reverse transcription PCR analysis
      revealed expression of the buISG15 in the uterine endometrium, corpus luteum
      (CL), corpus hemorrhagicum and oviduct. Quantitative Real Time PCR (RTqPCR)
      analysis also confirmed the constitutive expression of the buISG15 in the uterine
      endometrium during different stages (i.e. estrus, diestrus and proestrus) of
      estrous cycle and also during early (~d 30-40) pregnancy. Western blot analysis
      of the endometrial extract from both estrous cyclic as well as pregnant buffalo
      demonstrated the presence of only conjugated ISG15 which was >40 kDa. ISG15 mRNA
      and immune-reactive proteins were localized in the stromal as well as glandular
      epithelial cells of the uterine endometrium of estrous cyclic as well as pregnant
      buffalo. However, there was no significant difference in amount of ISG15 mRNA
      across the different reproductive phases. To conclude, this study will be helpful
      for the further understanding of the roles of the ISG15 in pregnancy of buffalo
      cows.

PMID- 22871330
TI  - Intracytoplasmic sperm injection (ICSI) in small ruminants.
AB  - Small ruminants are an important component of the global production systems of
      meat and wool, and their reproductive biology is well known. However, the
      incorporation of assisted reproduction techniques (ART) in the production systems
      of small ruminants is not as well developed as for other domestic species.
      Normally, production systems that incorporate ARTs are restricted to artificial
      insemination or in vivo embryo transfer. Intracytoplasmic sperm injection (ICSI)
      is one of the ARTs techniques reported for small ruminants and consists of the
      injection of spermatozoa inside an oocyte, bypassing the natural process of sperm
      oocyte interaction. In goats and sheep, there are few live births by ICSI
      reported, with no reports from other species of small ruminants. Currently, there
      has not been intensive research about ICSI in small ruminants. However, ICSI has
      potentially important applications in animal production systems, primarily its
      use with semen of valued animals, with epididymal sperm, in the fertilization of
      prepubertal or cryopreserved oocytes. Other applications include more advanced
      techniques, such as transgenic-ICSI or its combination with spermatogonial
      transplantation. In this article, we review the "state of the art" of this
      technique in small ruminants including its historical development, research needs
      for its improvement and future applications.

PMID- 22871331
TI  - The polycomb group protein EED varies in its ability to access the nucleus in
      porcine oocytes and cleavage stage embryos.
AB  - Chromatin-modifying complexes serve essential functions during mammalian
      embryonic development. Polycomb group proteins EED, SUZ12, and EZH2 have been
      shown to mediate methylation of the lysine 27 residue of histone protein H3
      (H3K27), an epigenetic mark that is linked with transcriptional repression. H3K27
      trimethylation has been shown to be present on chromatin in mature porcine
      oocytes, pronuclear and 2-cell stage embryos, with H3K27 trimethylation
      decreasing at the 4-cell stage and not detectable in blastocyst stage embryos.
      The goals of this study were to determine the intracellular localization of the
      polycomb group protein EED in porcine oocytes and cleavage stage porcine embryos
      produced by in vitro fertilization and to determine the binding abilities of
      karyopherin alpha subtypes toward EED. Our results revealed that EED had a strong
      nuclear localization in 4-cell and blastocyst stage embryos and a strong
      perinuclear staining in GV-stage oocytes; EED was not detectable in the nuclei of
      pronuclear or 2-cell stage embryos. An in vitro binding assay was performed to
      assess the ability of EED to interact with a series of karyopherin alpha
      subtypes; results from this experiment revealed that EED can interact with
      several karyopherin alpha subtypes, but with varying degrees of affinity.
      Together these data indicate that EED displays a dynamic change in intracellular
      localization in progression from immature oocyte to cleavage stage embryo and
      that EED possess differing in vitro binding affinities toward individual
      karyopherin alpha subtypes, which may in part regulate the nuclear access of EED
      during this window of development.

PMID- 22871332
TI  - Clinical and reproductive consequences of using BVDV-contaminated semen in
      artificial insemination in a beef herd in Argentina.
AB  - The current report was prompted by an atypical outbreak of mucosal disease that
      occurred in a beef herd in the southwestern part of Buenos Aires Province,
      Argentina, where a total of 9/41 (21.9%) yearling bulls died. Blood samples from
      73 bulls and 189 heifers were tested for evidence of persistent BVDV infection
      with Bovine Viral Diarrhea Virus (BVDV). Non-cytopathic BVDV was isolated from 7
      (9.6%) 24- to 36-month-old bulls, and 3 (1.6%) 36-month-old heifers. Non
      cytopathic BVDV was also detected in the seminal plasma of three of six
      persistently infected (PI) bulls. Furthermore, a 171 bp genomic fragment of BVDV
      was consistently detected by nested RT-PCR in one of the two samples of the
      commercial semen used for artificial insemination, indicating that this semen
      could be a possible source of infection for the whole herd. To evaluate the
      possible reproductive consequences of PI heifers and bulls, ovaries and semen
      were obtained from PI cattle for in vitro assays. The in vitro fertilization of
      oocytes with semen from PI bulls was associated with decreased cleavage and
      embryo development rates. Additionally, non-cytopathic BVDV was isolated from the
      follicular fluid of PI heifers. Genetic typing revealed that all isolates BVDV
      from the present study had a high percentage of homology and that all of the
      fragments from the RT-PCR clearly fit with the BVDV 1b cluster. These findings
      confirm the negative impact that BVDV can have on the reproductive performance of
      cattle and the importance of applying the proper sanitary controls to minimize
      the risk of BVDV infection.

PMID- 22871333
TI  - Long-term safety and efficacy of eslicarbazepine acetate as adjunctive therapy in
      the treatment of partial-onset seizures in adults with epilepsy: results of a 1
      year open-label extension study.
AB  - OBJECTIVE: To evaluate the long-term safety, tolerability and efficacy of once
      daily eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial
      onset seizures. METHODS: One-year open-label extension (OLE) study with ESL in
      patients who completed a randomised, double-blind placebo-controlled trial (study
      BIA-2093-302; Epilepsy Res. 89 (2010) 278-285). Starting dose was 800 mg once
      daily, for 4 weeks; thereafter, dose could be individualised within the 400-1,200
      mg range. Doses of concomitant antiepileptic drugs were to be kept stable.
      RESULTS: Overall, 325 patients were enrolled (intent-to-treat population); 223
      (68.6%) patients completed 1-year of treatment. ESL median dose was 800 mg once
      daily. Compared to the baseline period of the double-blind study completed prior
      to this OLE study, median seizure frequency decreased by 32% in weeks 1-4, and
      between 37% and 39% thereafter. The responder rate (seizure reduction >= 50%) was
      37% during weeks 1-4 and thereafter ranged between 38% and 42% per 12-week
      interval. Proportion of seizure-free patients per 12-week interval ranged between
      5% and 11%. Improvements from baseline in several Quality of Life in Epilepsy
      Inventory-31 (QOLIE-31) and Montgomery Asberg Depression Rating Scale (MADRS)
      scores were observed. Adverse events (AEs) were reported by 83% of patients. AEs
      occurring in >= 10% of patients were dizziness, headache and somnolence. AEs were
      usually of mild to moderate intensity. CONCLUSION: In this study, ESL
      demonstrated a sustained therapeutic effect and was well tolerated during 1-year
      add-on treatment of adults with partial-onset seizures. Additionally, significant
      improvements in quality of life domains and depressive symptoms were observed
      under long-term treatment with once-daily ESL.

PMID- 22871334
TI  - Plasma amino acid levels discriminate between control subjects and mildly
      depressed elderly women.
AB  - BACKGROUND AND AIMS: Depression is the most common of all psychiatric disorders
      and the role of amino acid transmitters in this pathology has been recently
      studied. We undertook this study to investigate if the plasma levels of L
      arginine, L-citrulline, L-glutamic acid, L-glutamine, L-asparagine and other
      amino acids, the L-citrulline/L-arginine and the L-tyrosine/L-phenylalanine
      ratios, and the nitrite levels are modified in mildly depressed women and if such
      changes are related to olfactory dysfunction. METHODS: Plasma samples were
      obtained from elderly female subjects (n = 21) with mild depression and (n = 48)
      controls. Amino acids were analyzed with high-performance liquid chromatography,
      plasma nitrite levels were measured using the Griess method, and olfactory
      performance was assessed by the combined testing of odor identification, odor
      discrimination, odor recognition, and the olfactory threshold. RESULTS: Compared
      to controls, depressed patients had a significantly higher concentration of L
      arginine and a significantly lower L-citrulline/L-arginine ratio when the effect
      of other variables is not taken into account. A logistic regression model allowed
      us to identify two risk factors for mild depression, L-arginine and L-glutamic
      acid, and two protective factors, L-asparagine and the L-tyrosine/L-phenylalanine
      ratio. Additionally, a significant increase in nitrite levels in depressed women
      was found. No significant differences were found between the percentage of
      depressed and control women that identified the odors. CONCLUSIONS: We identified
      that the amino acids L-arginine and L-glutamic acid are risk factors for mild
      depression, whereas L-asparagine and the L-tyrosine/L-phenylalanine ratio are
      protective factors.

PMID- 22871335
TI  - Exploring psychotic symptoms: a comparison of motor related neuronal activation
      during and after acute psychosis.
AB  - BACKGROUND: Delusions and hallucinations are classic positive symptoms of
      schizophrenia. A contemporary cognitive theory called the 'forward output model'
      suggests that the misattribution of self-generated actions may underlie some of
      these types of symptoms, such as delusions of control - the experience of self
      generated action being controlled by an external agency. In order to examine the
      validity of this suggestion, we performed a longitudinal functional magnetic
      resonance imaging (fMRI) study examining neuronal activation associated with
      motor movement during acute psychosis. METHODS: We studied brain activation using
      fMRI during a motor task in 11 patients with schizophrenia and 9 healthy
      controls. The patient group was tested at two time points separated by 6-8 weeks.
      RESULTS: At initial testing, the patient group had a mean Positive and Negative
      Syndrome Scale score of 56.3, and showed significantly increased activation
      within the left inferior parietal lobe (IPL) compared to controls. Patients
      reported significantly decreased positive symptoms at 6-8 week followup and IPL
      activation had returned to normal. Our results demonstrate that first-rank
      positive symptoms are associated with hyperactivation in the secondary
      somatosensory cortex (IPL). CONCLUSIONS: These findings lend further credence to
      the theory that a dysfunction in the sensory feedback system located in the IPL,
      and which is thought to underlie our sense of agency, may contribute to the
      aetiology of delusions of control.

PMID- 22871336
TI  - Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with
      increased risk of treatment failure using standard chemotherapy protocols.
AB  - BACKGROUND: The mechanisms responsible for chemoresistance in patients with
      refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette
      (ABC) transporters confer multidrug resistance in various cancers and ABCC1
      overexpression has been shown to contribute to drug resistance in the CHL cell
      line, KMH2. FINDINGS: We analyzed for expression of five ABC transporters ABCB1,
      ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment
      tumor specimens obtained from patients with CHL. All patients received first-line
      standard chemotherapy with doxorubicin (Adriamycin(r)), bleomycin, vinblastine,
      and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and
      Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by
      HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2
      and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and
      was marginally associated with poorer failure-free survival (p = 0.06).
      Multivariate analysis after adjusting for hemoglobin and albumin levels and age
      showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk
      of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028).
      CONCLUSIONS: Expression of ABCC1 by HRS cells in CHL patients predicts a higher
      risk of treatment failure and is marginally associated with poorer failure-free
      survival using standard frontline chemotherapy regimens.

PMID- 22871338
TI  - Method of removal of volatile organic compounds by using wet scrubber coupled
      with photo-Fenton reaction--preventing emission of by-products.
AB  - The photo-Fenton reaction was applied as a novel method for the removal of
      volatile organic compounds (VOCs) in the gas phase, and its effectiveness was
      experimentally examined. In conventional VOCs removal methods using a
      photocatalyst or ozone, VOCs are oxidized in the gas phase. Therefore,
      incompletely oxidized intermediates, which may have adverse effects on health,
      are likely to contaminate the treated air. On the other hand, in the VOCs removal
      method developed in this study, because the VOCs are oxidized in the liquid phase
      by the photo-Fenton reaction, any incompletely oxidized intermediates produced
      are confined to the liquid phase. As a result, the contamination of the treated
      air by these harmful intermediates can be prevented. Using a semi-batch process,
      it was found that the removal efficiency for toluene in a one-pass test
      (residence time of 17s) was 61%, for an inlet toluene gas concentration of 930
      ppbv, an initial iron ion concentration of 20 mg L(-1), and an initial hydrogen
      peroxide concentration of 630 mg L(-1). The removal efficiency was almost
      constant as long as H(2)O(2) was present in the solution. Proton transfer
      reaction mass spectrometry analysis confirmed the absence of any incompletely
      oxidized intermediates in the treated air.

PMID- 22871337
TI  - Targeting autophagy for the treatment of liver diseases.
AB  - Autophagy is a lysosomal degradation pathway that can degrade bulk cytoplasm and
      superfluous or damaged organelles, such as mitochondria, to maintain cellular
      homeostasis. It is now known that dysregulation of autophagy can cause
      pathogenesis of numerous human diseases. Here, we discuss the critical roles that
      autophagy plays in the pathogenesis of liver diseases such as non-alcoholic and
      alcoholic fatty liver, drug-induced liver injury, protein aggregate-related liver
      diseases, viral hepatitis, fibrosis, aging and liver cancer. In particular, we
      discuss the emerging therapeutic potential by pharmacological modulation of
      autophagy for these liver diseases.

PMID- 22871339
TI  - Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and
      VDR in placentas from normal and preeclamptic pregnancies.
AB  - Vitamin D insufficiency/deficiency during pregnancy has been linked to increased
      risk of preeclampsia. Placenta dysfunction plays an important role in the
      pathogenesis of this pregnancy disorder. In this study, we tested the hypothesis
      that disturbed vitamin D metabolism takes place in preeclamptic placentas.
      Protein expressions of vitamin D binding protein (VDBP), 25-hydroxylase (CYP2R1),
      1alpha-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D receptor
      (VDR) were examined in placentas from normotensive and preeclamptic pregnancies.
      By immunostaining we found that in normal placenta VDBP, CYP24A1, and VDR
      expressions are localized mainly in trophoblasts, whereas CYP2R1 and CYP27B1
      expressions are localized mainly in villous core fetal vessel endothelium.
      Protein expressions of CYP2R1 and VDR are reduced, but CYP27B1 and CYP24A1
      expressions are elevated, in preeclamptic compared with normotensive placentas.
      Because increased oxidative stress is an underlying pathophysiology in placental
      trophoblasts in preeclampsia, we further determined whether oxidative stress
      contributes to altered vitamin D metabolic system in placental trophoblasts.
      Trophoblasts isolated from normal-term placentas were treated with hypoxic
      inducing agent CoCl(2), and protein expressions of VDBP, CYP2R1, CYP27B1,
      CYP24A1, and VDR were determined. We found that hypoxia-induced downregulation of
      VDBP, CYP2R1, and VDR and upregulation of CYP27B1 and CYP24A1 expressions were
      consistent with that seen in preeclamptic placentas. CuZnSOD expression was also
      downregulated in trophoblasts treated with CoCl(2). These results provide direct
      evidence of disrupted vitamin D metabolic homeostasis in the preeclamptic
      placenta and suggest that increased oxidative stress could be a causative factor
      of altered vitamin D metabolism in preeclamptic placentas.

PMID- 22871340
TI  - Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like
      peptide-1 secretion from murine intestinal L cells.
AB  - The antidiabetic intestinal L cell hormone glucagon-like peptide-1 (GLP-1)
      enhances glucose-dependent insulin secretion and inhibits gastric emptying. GLP-1
      secretion is stimulated by luminal oleic acid (OA), which crosses the cell
      membrane by an unknown mechanism. We hypothesized that L cell fatty acid
      transport proteins (FATPs) are essential for OA-induced GLP-1 release. Therefore,
      the murine GLUTag L cell model was used for immunoblotting, [(3)H]OA uptake
      assay, and GLP-1 secretion assay as determined by radioimmunoassay following
      treatment with OA +/- phloretin, sulfo-N-succinimidyl oleate, or siRNA against
      FATP4. FATP4(-/-) and cluster-of-differentiation 36 (CD36)(-/-) mice received
      intraileal OA, and plasma GLP-1 was measured by sandwich immunoassay. GLUTag
      cells were found to express CD36, FATP1, FATP3, and FATP4. The cells demonstrated
      specific (3)H[OA] uptake that was dose-dependently inhibited by 500 and 1,000 MUM
      unlabeled OA (P < 0.001). Cell viability was not altered by treatment with OA.
      Phloretin and sulfo-N-succinimidyl oleate, inhibitors of protein-mediated
      transport and CD36, respectively, also decreased [(3)H]OA uptake, as did
      knockdown of FATP4 by siRNA transfection (P < 0.05-0.001). OA dose-dependently
      increased GLP-1 secretion at 500 and 1,000 MUM (P < 0.001), whereas phloretin,
      sulfo-N-succinimidyl oleate, and FATP4 knockdown decreased this response (P <
      0.05-0.01). FATP4(-/-) mice displayed lower plasma GLP-1 at 60 min in response to
      intraileal OA (P < 0.05), whereas, unexpectedly, CD36(-/-) mice displayed higher
      basal GLP-1 levels (P < 0.01) but a normal response to intraileal OA. Together,
      these findings demonstrate a key role for FATP4 in OA-induced GLP-1 secretion
      from the murine L cell in vitro and in vivo, whereas the precise role of CD36
      remains unclear.

PMID- 22871341
TI  - Substrate nanotexture and hypergravity through centrifugation enhance initial
      osteoblastogenesis.
AB  - Mimicking the structural nanomolecular extracellular matrix with synthetically
      designed nanosized materials is a relatively new approach, which can be applied
      in the field of bone tissue engineering. Likewise, bone tissue-engineered
      constructs can be aided in their development by the use of several types of
      mechanical stimuli. In this study, we wanted to combine nanotextured biomaterials
      and centrifugation in one multifactorial system. Mesenchymal stem cells were
      isolated from rat bone marrow, and cultured on a nanogrooved polystyrene
      substrate (200-nm-wide pitch with a depth of 50 nm). Constant centrifugation of
      10 g was applied to cells up to 7 days. Results showed that on a nanogrooved
      substrate osteoblast-like cells align parallel to the groove direction.
      Centrifugation of 10 g also affected cell morphology on a smooth surface.
      Moreover, cell alignment was significantly reduced for cells grown on nanogrooved
      substrates, which were subsequently subjected to centrifugation. Independently,
      both stimuli increased the number of cells after 7 days of culture. However, when
      both stimuli were combined, an additive effect on cell number was observed,
      followed by an enhanced effect on osteocalcin mRNA expression and matrix
      mineralization. In conclusion, biomaterial surface modification as well as
      centrifugation are effective means to enhance bone cell behavior, moreover,
      readily available to many tissue engineers.

PMID- 22871342
TI  - Surgical correction of a congenital coronary arterial fistula and a massive sinus
      of Valsalva aneurysm.
AB  - The case of a 22-year old male patient who presented with a congenital coronary
      arterial fistula from the right coronary artery to the right ventricle is
      described. The arterial fistula had led to an aneurysm of the right sinus of
      Valsalva and the proximal right coronary artery. The aneurysm was incised from
      the aorta and the fistula closed with a pericardial patch. The diameter of the
      aneurysm was reduced by plication. Successful occlusion of the fistula and the
      competence of the aortic valve were confirmed by transoesophageal
      echocardiography.

PMID- 22871344
TI  - Job demands as a potential modifier of the association between testosterone
      deficiency and andropause symptoms in Japanese middle-aged workers: a cross
      sectional study.
AB  - OBJECTIVE: The present study investigated whether job demands modify the
      association between low levels of testosterone and andropause symptoms. STUDY
      DESIGN: Participants were Japanese middle-aged workers in a middle-size company.
      Blood samples were drawn to determine serum levels of testosterone. Participants
      completed a self-report questionnaire that included 5 items from the Job Content
      Questionnaire (JCQ) that assesses job demands, the Aging Males' Symptoms (AMS)
      scale as well as questions regarding health behaviors and history of disease.
      Analysis of data was limited to the 183 men who completed all components of the
      questionnaire and provided blood samples (mean age=51.9 years, SD=7.7, age range
      34-67 years). MAIN OUTCOME MEASURES: The AMS which comprises three symptom sub
      scales: somatic, psychological, and sexual. RESULTS: Men with low testosterone
      levels (<349 ng/dL) had more psychological andropause symptoms than those with
      high levels. In men with high psychological job demands, compared to men with low
      job demands, testosterone levels were positively associated with the total score
      for andropause symptoms and scores for somatic and psychological symptoms.
      CONCLUSIONS: Level of job demands may intensify the effect of testosterone
      deficiency on andropause symptoms.

PMID- 22871345
TI  - Association of functional dopamine-beta-hydroxylase (DBH) 19 bp
      insertion/deletion polymorphism with smoking severity in male schizophrenic
      smokers.
AB  - Recent evidence suggests that a dopamine beta-hydroxylase (DBH) polymorphism may
      play a role in determining an individual's predisposition to developing nicotine
      dependence. The mechanism for such an association may reflect nicotine's
      mediation of drug reward in the brain through actions on dopamine, a key mediator
      of drug reward. Because schizophrenia patients have usually high rates of
      nicotine use, they are a model group to study such an association. In this study,
      we hypothesized that the functional polymorphism of DBH (DbetaH5'-Ins/Del) was
      associated with smoking in patients with schizophrenia. This polymorphism was
      genotyped in 636 chronic male schizophrenia (smoker/nonsmoker=490/146) and 396
      male controls (smoker/nonsmoker=231/165) using a case-control design. The
      cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician
      administered questionnaires and the Fagerstrom Test for Nicotine Dependence
      (FTND). The results showed no significant differences in DBH 5'-Ins/Del genotype
      and allele distributions between the patients and healthy controls or between
      smokers and nonsmokers in either patients or healthy controls alone. However,
      schizophrenic smokers with the Del allele smoked fewer cigarettes each day and
      had lower FTND score than those with Ins/Ins genotype. These results suggest that
      the DBH 5'-Ins/Del polymorphism may influence smoking severity among
      schizophrenic smokers.

PMID- 22871346
TI  - Further evidence for the association of genetic variants of ZNF804A with
      schizophrenia and a meta-analysis for genome-wide significance variant rs1344706.
AB  - Recent accumulating evidence has indicated that ZNF804A (zinc finger protein
      804A) may be one of the most robustly implicated genes in schizophrenia. In this
      report, we examined ZNF804A single nucleotide polymorphisms (SNPs) encompassing
      exon 4 by performing an association study that used a Han Chinese sample
      comprised of 492 schizophrenia patients and 516 healthy control subjects. A meta
      analysis based on previous studies was also performed. For markers rs4667000 and
      rs1366842, significant differences in allele frequencies were found between cases
      and controls (Mantel-Haenszel corrected P=0.014 and P=0.025, respectively).
      Analysis of haplotype rs61739290-rs1366842 showed significant association with
      schizophrenia (global P=0.0018). Moreover, several other two-, three-, and four
      SNP tests of haplotype association were also significant. A meta-analysis
      comprised of studies that utilized sample sets of either European and/or Han
      Chinese origin revealed statistically significant associations for two SNPs
      (rs1366842, P=0.002; and rs3731834, P=0.03) and schizophrenia. In addition, we
      observed a significant association between marker rsl344706 and schizophrenia
      (P<1.0*10(-5)) in combined populations. When we separately analyzed the studies
      by population, consistent and significant differences were found between cases
      and controls both in the European samples (P<1.0*10(-4)) and in the Chinese
      samples (P=0.03). In summary, we have added new evidence supporting the
      association between ZNF804A and schizophrenia in our Han Chinese sample. Further
      functional exploration of ZNF804A will greatly help us to elucidate the
      pathogenesis of schizophrenia and find promising new approaches for the treatment
      of this disorder.

PMID- 22871347
TI  - Finite element modelling of stapled colorectal end-to-end anastomosis: advantages
      of variable height stapler design.
AB  - The impact of surgical staplers on tissues has been studied mostly in an
      empirical manner. In this paper, finite element method was used to clarify the
      mechanics of tissue stapling and associated phenomena. Various stapling
      modalities and several designs of circular staplers were investigated to evaluate
      the impact of the device on tissues and mechanical performance of the end-to-end
      colorectal anastomosis. Numerical simulations demonstrated that a single row of
      staples is not adequate to resist leakage due to non-linear buckling and opening
      of the tissue layers between two adjacent staples. Compared to the single staple
      row configuration, significant increase in stress experienced by the tissue at
      the inner staple rows was observed in two and three rows designs. On the other
      hand, adding second and/or third staple row had no effect on strain in the tissue
      inside the staples. Variable height design with higher staples in outer rows
      significantly reduced the stresses and strains in outer rows when compared to the
      same configuration with flat cartridge.

PMID- 22871348
TI  - Sildenafil before total cavopulmonary connection.

PMID- 22871349
TI  - Optical coherence tomography in spontaneous coronary dissection and in the
      complications following percutaneous treatment.

PMID- 22871350
TI  - Confounder adjustment in vaccine safety studies: comparing three offset terms for
      case-centered approach.
AB  - The case-centered approach (CCA) can be useful in vaccine safety studies to
      adjust for time varying confounders, especially seasonality. The method compares
      the observed odds of vaccination in the time interval prior to the event with the
      expected odds of vaccination during this interval. The log of the expected odds
      is included in the analysis model as an offset term and it is critical to
      correctly estimate vaccine effects. In a recent Zostavax((r)) safety study, we
      used three alternative sources of reasonable expectations for the offset term. We
      conducted a simulation study to compare the performance of the three offset terms
      with different types of seasonal confounders and at different degrees of
      confounding. The offset term calculated by modeling the timing of vaccination
      based on predictors such as age, sex and site resulted in the least biased
      estimate of relative risk (RR).

PMID- 22871351
TI  - A bivalent Neisseria meningitidis recombinant lipidated factor H binding protein
      vaccine in young adults: results of a randomised, controlled, dose-escalation
      phase 1 trial.
AB  - Neisseria meningitidis is a leading cause of meningitis and septicaemia, but a
      broadly-protective vaccine against endemic serogroup B disease is not licensed
      and available. The conserved, outer-membrane lipoprotein factor H binding protein
      (fHBP, also known as LP2086) is expressed as one of two subfamily variants in
      virtually all meningococci. This study investigated the safety, tolerability, and
      immunogenicity of a recombinant-expressed bivalent fHBP (r-fHBP) vaccine in
      healthy adults. Participants (N=103) aged 18-25 years were recruited into three
      ascending dose level cohorts of 20, 60, and 200MUg of a bivalent r-fHBP vaccine
      formulation and randomised to receive vaccine or placebo at 0, 1, and 6 months.
      The vaccine was well tolerated. Geometric mean titres (GMTs) for r-fHBP subfamily
      specific IgG antibodies increased 19-168-fold from pre-vaccination to post-dose 2
      in a dose level-dependent manner. In addition, robust serum bactericidal assay
      using human complement (hSBA) responses for strains expressing both homologous
      and heterologous fHBP variants were observed. After three vaccinations, 16-52% of
      the placebo group and 47-90%, 75-100%, and 88-100%, of the 20, 60, and 200MUg
      dose levels, respectively, had seroprotective (>= 1:4) hSBA titres against six
      serogroup B strains. The bivalent r-fHBP vaccine was well tolerated and induced
      robust bactericidal activity against six diverse serogroup B strains in young
      adults at the 60 and 200MUg dose levels.

PMID- 22871352
TI  - Polymorphisms in key innate immune genes and their effects on measles vaccine
      responses and vaccine failure in children from Mozambique.
AB  - Despite an effective vaccine, measles remains a major health problem globally,
      particularly in developing countries. More than 30% of children show primary
      vaccine failure and therefore remain vulnerable to measles. Genetic variation in
      key innate pathogen recognition receptors, such as the measles cell entry
      receptors CD46 and SLAM, measles attachment receptor DC-SIGN, the antiviral toll
      like receptors (TLR)3, TLR7 and TLR8, and the cytosolic antiviral receptor RIG-I,
      may significantly affect measles IgG antibody responses. Measles is still highly
      prevalent in developing countries such as those in Africa however there is no
      previous data on the effect of these innate immune genes in a resident African
      population. Polymorphisms (n=29) in the candidate genes were genotyped in a
      cohort of vaccinated children (n=238) aged 6 months-14 years from Mozambique,
      Africa who either had vaccine failure and contracted measles (cases; n=66) or
      controls (n=172). Contrasting previous associations with measles responses in
      Caucasians and/or strong evidence for candidacy, we found little indication that
      these key innate immune genes affect measles IgG responses in our cohort of
      Mozambican children. We did however identify that CD46 and TLR8 variants may be
      involved in the occurrence of measles vaccine failure. This study highlights the
      importance of genetic studies in resident, non-Caucasian populations, from areas
      where determining the factors that may affect measles control is of a high
      priority.

PMID- 22871353
TI  - Protective efficacy of Mycobacterium indicus pranii against tuberculosis and
      underlying local lung immune responses in guinea pig model.
AB  - Tuberculosis kills two million people each year. As the current vaccine BCG fails
      to prevent adult cases of TB, an improved vaccine and/or vaccination strategy is
      urgently needed to combat TB. Previously we reported the higher protective
      efficacy of Mycobacterium indicus pranii (MIP), formerly known as Mycobacterium w
      (M.w) as compared to BCG in murine model of TB. In this study we further
      evaluated the protective efficacy of MIP in guinea pig model of TB. Modulation of
      post infection immune response was analyzed in the lungs of MIP immunized and
      control groups. We found reduced bacterial loads, improved pathology and
      organized granulomatous response at different post infection time points in the
      MIP-immunized group as compared to the BCG-immunized group. Combined results
      suggest that MIP-immunization results in heightened protective Th1 response as
      compared to BCG group, early after infection with M.tb and a balanced Th1 versus
      immunosuppressive response at late chronic stage of infection. The study
      demonstrates the higher antigen presenting cells function both inside the
      granuloma as well as in the single cell suspension of the lung in the MIP
      immunized group. We further demonstrate that live MIP is safe to use in vivo as
      we observed quick clearance of MIP from the body and no untoward reaction was
      found. Aerosol route of immunization provided higher protection. Further this
      study provides evidence that MIP-immunization gives significantly better long
      term protection as compared to BCG against TB.

PMID- 22871354
TI  - Analysing arrangements for cross-border mobility of patients in the European
      Union: a proposal for a framework.
AB  - This paper proposes a framework for analyzing arrangements set up to facilitate
      cross-border mobility of patients in the European Union. Exploiting both
      conceptual analysis and data from a range of case studies carried out in a number
      of European projects, and building on Walt and Gilson's model of policy analysis,
      the framework consists of five major components, each with a subset of categories
      or issues: (1) The actors directly and indirectly involved in setting up and
      promoting arrangements, (2) the content of the arrangements, classified into four
      categories (e.g. purchaser-provider and provider-provider or joint cross-border
      providers), (3) the institutional framework of the arrangements (including the
      underlying European and national legal frameworks, health systems'
      characteristics and payment mechanisms), (4) the processes that have led to the
      initiation and continuation, or cessation, of arrangements, (5) contextual
      factors (e.g. political or cultural) that impact on cross-border patient mobility
      and thus arrangements to facilitate them. The framework responds to what is a
      clearly identifiable demand for a means to analyse these interrelated concepts
      and dimensions. We believe that it will be useful to researchers studying cross
      border collaborations and policy makers engaging in them.

PMID- 22871355
TI  - [Minimally invasive approach of extramedullary intradural spinal tumours. Review
      of 30 cases].
AB  - OBJECTIVE: To analyse the safety and effectiveness of a microsurgical unilateral
      approach in minimally invasive surgery of extramedullary, intradural spinal
      tumours. MATERIALS AND METHODS: This was a retrospective study of 29 patients
      with 30 extramedullary, intradural spinal tumours approached through unilateral
      laminectomy -hemilaminectomy. Epidemiological data, location and histology of the
      lesions and radiological and clinical evolution of the patients were recorded.
      The Nurick scale was used in the preoperative and postoperative functional
      assessment conducted during the last follow-up consultation. The mean age of
      patients was 60 years and there was a predominance of the female gender. The mean
      time elapsed from the onset of symptoms to diagnosis was 11.6 months. Sensitive
      and motor deficits were the most common symptoms. Meningioma was the most
      frequent lesion, followed by neurinoma and ependymoma. The most commonly affected
      level was the dorsal, followed by the lumbar and cervical. RESULTS: Total
      resection was performed in all cases except for one cervical neurinoma with
      extraforaminal extension. Three patients presented postoperative complications 
      cerebrospinal fluid fistula, asymptomatic pseudomeningocele and postoperative
      functional worsening- which were resolved with conservative treatment. The mean
      time of clinical and radiological follow-up was 33.4 months, with no tumoural
      recurrences being observed except for two cases of meningiomas. After the follow
      up period, patients without functional disorders remained stable and all patients
      with functional disorders presented a clinical improvement of at least one point
      in the Nurick scale. CONCLUSIONS: We consider that the microsurgical unilateral
      approach is a safe and effective technique for the resection of most
      extramedullary, intradural spinal tumours.

PMID- 22871356
TI  - Quantitative determination of matrix Gla protein (MGP) and BMP-2 during the
      osteogenic differentiation of human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Matrix Gla protein (MGP) has been recognized as a
      potent calcification inhibitor and a regulator for bone morphogenetic protein-2
      (BMP-2). The periodontal ligament (PDL) is a non-mineralized connective tissue
      located between two mineralized tissues, the cementum and the alveolar bone.
      However, the mechanism by which PDL prevents mineralization has yet to be
      defined. This study aims to examine the expression pattern of MGP and BMP-2
      during human periodontal ligament cells (hPDLCs) osteogenic differentiation in
      vitro, preliminarily exploring their roles in this process. MATERIALS AND
      METHODS: hPDLCs were obtained and cultured in mineralizing medium. The expression
      of MGP and BMP-2 was confirmed by RT-PCR and immunofluorescence staining. In the
      process of osteogenic induction, alkaline phosphatase (ALP) activity,
      extracelluar calcium deposition, and mineralized nodules were measured.
      Quantitative real-time RT-PCR was performed to evaluate mRNA expression of MGP,
      BMP-2 and osteogenic marker genes, including ALP, bone sialoprotein (BSP), type I
      collagen (COLI), osteocalcin (OCN), and runt-related transcription factor 2
      (Runx2). The protein expression of MGP and BMP-2 was analyzed by western
      blotting. RESULTS: Co-localization of MGP and BMP-2 was visualized in hPDLCs.
      After osteogenic induction, ALP activity, calcium deposition, mineralized
      nodules, and osteogenic marker genes were significantly up-regulated. mRNA
      expression of MGP and BMP-2 generally decreased, although MGP mRNA increased on
      day 14 and 21 compared with the control, and protein expression of MGP and BMP-2
      was down-regulated. CONCLUSION: Our results indicate that MGP might regulate
      hPDLCs osteogenic differentiation which might keep a potential relationship with
      BMP-2 in this process.

PMID- 22871357
TI  - Cyclic stretch influenced expression of membrane connexin 43 in human periodontal
      ligament cell.
AB  - OBJECTIVE: Periodontal ligament (PDL) cells play an important role in preserving
      periodontal homeostasis and periodontal remodelling in response to mechanical
      stimulations. Gap junction intercellular communication (GJIC) is essential for
      homeostasis and many other biological processes of multicellular organisms. While
      the role of GJIC in mechanotransduction of PDL cells remains largely unknown. In
      the present study, we examined the influence of cyclic stretch on the expression
      of membrane gap junction protein connexin 43 (Cx43) in cultured human PDL cells.
      DESIGN: Cultured human PDL cells were exposed to 1%, 10% and 20% stretch strains
      for 0.5 h, 1 h and 24 h. Then the membrane Cx43 protein expression was measured
      by flow cytometry and the Cx43 mRNA level was measured by real-time polymerase
      chain reaction. RESULTS: Half hour and 1 h cyclic stretches with strains up to
      20% did not change the expression of membrane Cx43 protein, while 24 h cyclic
      stretches with 10% and 20% strains down-regulated the expression of membrane Cx43
      protein in a strain magnitude-dependent manner. Furthermore, cyclic stretch also
      changed the Cx43 mRNA level and induced realignment in cells. CONCLUSION: The
      present research provide the first evidence that cyclic stretch influenced the
      membrane Cx43 protein expression in cultured human PDL cells.

PMID- 22871358
TI  - BVDV: a pestivirus inducing tolerance of the innate immune response.
AB  - Animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) retain
      a strain-specific B- and T-cell immunotolerance. Pestiviral RNA triggers
      interferon (IFN) synthesis, and the viral RNase E(rns) inhibits IFN expression
      induced by extracellular viral RNA. In addition, N(pro) promotes the degradation
      of the transcription factor IRF-3, which effectively blocks IFN expression in
      BVDV-infected cells. As not all the potential target cells are infected in PI
      animals, these are 'chimeric' with respect to BVDV. This suggests that N(pro) and
      E(rns) are non-redundant IFN antagonists that act in infected and non-infected
      cells, respectively. Moreover, E(rns) may take a paradoxical function, both as
      virulence as well as "attenuation" factor: The former by preventing the
      activation of the innate and, consequently, of the adaptive immune system, the
      latter by minimizing the detrimental effects of systemic IFN production. Thus,
      BVDV maintains "self-tolerance" by avoiding the induction of IFN while itself
      being largely resistant to it without, however, interfering with the IFN action
      against unrelated viruses ('nonself'). This unique extension of 'self' to a virus
      suggests that the host's own RNases may have evolved as a guard against
      inadvertent activation of the innate immune system by host RNA, thus establishing
      a state of "innate tolerance".

PMID- 22871359
TI  - Toward the end of blind prostate biopsies?

PMID- 22871361
TI  - Recombinant expression and purification of heparin binding proteins: midkine and
      pleiotrophin from Escherichia coli.
AB  - Midkine (MDK) and Pleiotrophin (PTN) belong to a class of heparin-binding growth
      factors and are highly expressed in a number of cancers. Bioactive and
      recombinant MDK and PTN are critical reagent for cancer drug discovery studies.
      MDK and PTN belong to a newly evolving family of secreted neurotrophic and
      developmentally regulated heparin-binding molecules. PTN is related to MDK with
      45% sequence identity and both proteins have been shown to be involved in
      promoting neurite outgrowth. MDK is a cysteine-rich 13kDa protein containing five
      disulfide bonds and PTN is 19kDa protein containing ten disulphide bonds. In this
      study, we expressed recombinant human MDK (rhMDK), mouse MDK (rmMDK) and human
      pleiotrophin (rhPTN) in Escherichia coli BL21(DE3)pLysS strain. Soluble rhMDK,
      rmMDK and rhPTN were expressed at a high-level in this strain and the protein was
      purified (~90%) by a one-step purification using heparin affinity chromatography.
      A total of 4mg purified MDK and 7mg of purified PTN were obtained with the
      overall yield from 1L of bacterial culture. Activity of purified rhMDK and rhPTN
      was confirmed by a cell proliferation assay using NIH3T3 cells.

PMID- 22871362
TI  - Impact of weekday social contact patterns on the modeling of influenza
      transmission, and determination of the influenza latent period.
AB  - Human social contact patterns show marked day-of-week variations, with a higher
      frequency of contacts occurring during weekdays when children are in school, and
      adults are in contact with co-workers, than typically occur on weekends. Using
      epidemic modeling, we show that using the average of social contacts during the
      week in the model yields virtually identical predictions of epidemic final size
      and the timing of the epidemic incidence peak as a model that incorporates
      weekday social contact patterns. This is true of models with a constant weekly
      average contact rate throughout the year, and also of models that assume
      seasonality of transmission. Our modeling studies reveal, however, that weekday
      social contact patterns can produce substantial weekday variations in an
      influenza incidence curve, and the pattern of variation is sensitive to the
      influenza latent period. The possible observability of weekday patterns in daily
      influenza incidence data opens up an interesting avenue of further inquiry that
      can shed light on the latent period of pandemic influenza. The duration of the
      latent period must be known with precision in order to design effective disease
      intervention strategies, such as use of antivirals. For a hypothetical influenza
      pandemic, we thus perform a simulation study to determine the number of cases
      needed to observe the weekday variation pattern in influenza epidemic incidence
      data. Our studies suggest that these patterns should be observable at 95%
      confidence in daily influenza hospitalization data from large cities over 75% of
      the time. Using 2009 A(H1N1) daily case data recorded by a large hospital in
      Santiago, Chile, we show that significant weekday incidence patterns are evident.
      From these weekday incidence patterns, we estimate the latent period of influenza
      to be [0.04, 0.60] days (95% CI). This method for determination of the influenza
      latent period in a community setting is novel, and unique in its approach. 

PMID- 22871363
TI  - [Adverse drug reactions in a paediatric intensive care unit].
AB  - OBJECTIVE: To determine ADR frequency and characteristics of ADR in a paediatric
      intensive care unit between may and june 2009. METHOD: All of the hospitalised
      children were under intensive pharmacosurveillance by means of daily analysis of
      their prescription profiles. The following patient characteristics were analysed:
      age, sex, drugs involved, affected organs and systems, triggered illness, adverse
      reaction mechanism, presence of polypharmacy, severity and course of the
      reaction. The following variables were recorded for adverse reactions: frequency,
      incidence in hospitalised children, incidence per 100 children/day and percentage
      of preventable reactions. RESULTS: Of the 123 hospitalised children, 24
      experienced at least one adverse reaction. The total number of identified adverse
      drug reactions was 45. Average age was 34 months, and 14 patients were
      male.Frequency was 36.6% (CI 95% 28.4-46.4). Adverse reaction average was
      calculated at 1.9 reactions per child. The ADR incidence rate per 100
      children/day was 10.4. There were 66 drugs involved; the most common drug groups
      were antiepileptics and diuretics. Drug reactions most frequently affected the
      metabolic and haematological systems. Of the reactions, 61% were preventable.
      Twelve reactions were severe and 1 patient died. CONCLUSIONS: Adverse reactions
      are a frequent health problem among critically ill children. There is a pressing
      need to create awareness and prevention strategies to decrease their frequency
      and severity.

PMID- 22871364
TI  - [Interstitial pneumonitis due to gemcitabine].

PMID- 22871365
TI  - [Romplostim in the treatment of immune thrombocytopenic purpura at a tertiary
      hospital].

PMID- 22871366
TI  - [Detection of prescription errors associated with an electronic prescription
      system].

PMID- 22871367
TI  - [Piperacillin-tazobactam in continuous or expanded perfusion vs intermittent
      perfusion].
AB  - OBJECTIVE: The primary objective of this review was to analyse the differences in
      efficacy between the administration of intermittent and continuous/expanded
      perfusion of piperacillin-tazobactam. Secondary objectives were to analyse the
      differences in safety, pharmacokinetic/pharmacodynamic parameters, and cost
      effectiveness between the two forms of administration. METHOD: We performed two
      different independent bibliographic searches. We encountered a total of 38
      articles, and the final number included in the study was 6. We analysed the
      articles and collected the following variables: design, treatment administered to
      each group, total number of patients and number of patients in each study,
      variables collected in each study, and results. RESULTS: We encountered
      significant differences in the primary variable in two of the six studies
      favouring continuous/expanded perfusion. The study by Lodise et al found
      differences (P=.04) in mortality (31.6% for intermittent perfusion vs 12.2% for
      continuous/expanded perfusion). The study by Lorente et al found differences
      (P=.001) in terms of clinical recovery (56.5% for intermittent perfusion vs 89.2%
      for continuous/expanded perfusion). As for secondary variables, we only found
      differences in one of the studies in relation to cost-effectiveness, in favour of
      the group who underwent continuous/expanded perfusion method. CONCLUSION: The
      analysed data suggest that continuous/expanded perfusion would be at least as
      effective as intermittent perfusion, and that it could be more effective in
      severe patients with infections from more resistant micro-organisms such as
      Pseudomonas aeruginosa. Additionally, this form of administration is more cost
      effective, at least in theory.

PMID- 22871368
TI  - Height preferences in humans may not be universal: evidence from the Datoga
      people of Tanzania.
AB  - Many studies in Western societies have shown that women prefer relatively taller
      men as potential partners, whereas men prefer women who are slightly shorter than
      themselves. Here, we discuss possible limitations of previous results within the
      context of the stimuli used (i.e., differences in the perceived body size of
      female silhouettes). Our results show that, at least in a Polish sample (N=231),
      modified stimuli did not essentially change the observed male-taller preferences.
      In contrast, we report height preferences in a traditional ethnic group, the
      Datoga people from Tanzania (N=107), in which men and women preferred extreme
      sexual dimorphism in stature (SDS) sets (i.e., men and women chose women much
      taller or much shorter than themselves). Thus, our data do not accord with the
      suggestion of a universal preference for taller men, but rather suggests that
      height preferences may be influenced by cultural, environmental, and ecological
      conditions.

PMID- 22871369
TI  - Safety of the long-acting neuraminidase inhibitor laninamivir octanoate hydrate
      in post-marketing surveillance.
AB  - Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase
      inhibitor (NAI) that completes treatment with only a single inhalation. It was
      launched in Japan in October 2010 as an anti-influenza agent. A post-marketing
      surveillance study was conducted in the 2010/2011 influenza season to assess the
      safety of this drug in clinical settings. Adverse drug reactions (ADRs) were
      observed in 50 patients (59 events) out of 3542 patients subjected to safety
      evaluation (incidence 1.41%). Commonly reported ADRs were psychiatric disorders
      (abnormal behaviour, etc.), gastrointestinal disorders (diarrhoea, nausea, etc.)
      and nervous system disorders (dizziness, etc.), with incidences of 0.48% (n=17),
      0.45% (n=16) and 0.17% (n=6), respectively. No serious ADRs occurred. ADRs
      usually emerged on the day on which laninamivir was inhaled (52.5%) and ADRs
      emerged within 3 days after inhalation in >90% of adversely affected patients.
      ADRs resolved or improved within 3 days in >85% of patients. The incidence of
      adverse events involving abnormal behaviour was 3.1% (30/959) among patients <10
      years of age, 0.7% (8/1088) among patients aged 10-19 years, 0.1% (2/1431) among
      adult patients aged 20-64 years and 0.0% (0/64) among patients aged >=65 years.
      It was confirmed that laninamivir is unlikely to cause delayed ADRs or a
      prolonged duration of ADRs despite this drug being a long-acting NAI.
      Furthermore, the incidence of ADRs was not found to have increased compared with
      that observed during clinical trials, and the types of ADR observed during this
      study were similar to those previously observed. Thus, laninamivir octanoate
      hydrate was confirmed to have no noticeable problem with safety.

PMID- 22871370
TI  - Correlation between oritavancin and vancomycin minimum inhibitory concentrations
      in staphylococci.

PMID- 22871371
TI  - Mutant prevention concentration of colistin alone and in combination with
      levofloxacin or tobramycin against multidrug-resistant Acinetobacter baumannii.

PMID- 22871372
TI  - Impacts of a long-term programme of active surveillance and chlorhexidine baths
      on the clinical and molecular epidemiology of meticillin-resistant Staphylococcus
      aureus (MRSA) in an Intensive Care Unit in Scotland.
AB  - Evidence is accumulating that active surveillance, when combined with appropriate
      infection control, is a successful measure for controlling hospital-acquired
      meticillin-resistant Staphylococcus aureus (MRSA). In this study, the impacts of
      a long-term control strategy of this type, including the use of chlorhexidine
      baths, on the clinical and molecular epidemiology of MRSA in the Intensive Care
      Unit of Aberdeen Royal Infirmary were investigated. Characterisation of 85
      sequential index MRSA isolates was performed using phenotypic methods
      (biotyping), antibiotic susceptibility testing and three genotypic methods
      (pulsed-field gel electrophoresis, spa typing and multilocus sequence typing)
      over a 4-year period. There was no evidence of loss in effectiveness of the
      control strategy over the study period. Compliance with screening remained high
      (>85%) throughout and there was no significant increase in the prevalence of MRSA
      detected in surveillance (P=0.43 for trend) or clinical cultures (P=0.79). There
      were no significant trends in rates of other index surveillance organisms
      (P>0.5). Results of the three typing methods were in general agreement with three
      prevalent MRSA clones [clonal complex 22 (CC22), CC30 and CC45]. CC22 emerged as
      the dominant clonal complex alongside a significant decline in CC30 (P=0.002).
      CC45 was significantly more likely to be positive in glycopeptide resistance
      screens (P<0.001). There was no increase in antibiotic or chlorhexidine
      resistance. Long-term chlorhexidine bathing was not associated with any
      detectable loss of efficacy or increase in resistance in MRSA or with any
      increase in infection with other organisms. Changing clonal epidemiology occurred
      with no overall change in the prevalence of MRSA.

PMID- 22871373
TI  - Comments to Ocampos-Martinez et al. on one of the definitions of kidney failure,
      and on how to reduce the delay in reaching desired plasma concentrations of
      vancomycin.

PMID- 22871374
TI  - Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from
      polyurethane flexible foam.
AB  - Polyurethanes (PU) are polymers made from diisocyanates and polyols for a variety
      of consumer products. It has been suggested that PU foam may contain trace
      amounts of residual toluene diisocyanate (TDI) monomers and present a health
      risk. To address this concern, the exposure scenario and health risks posed by
      sleeping on a PU foam mattress were evaluated. Toxicity benchmarks for key non
      cancer endpoints (i.e., irritation, sensitization, respiratory tract effects)
      were determined by dividing points of departure by uncertainty factors. The
      cancer benchmark was derived using the USEPA Benchmark Dose Software. Results of
      previous migration and emission data of TDI from PU foam were combined with
      conservative exposure factors to calculate upper-bound dermal and inhalation
      exposures to TDI as well as a lifetime average daily dose to TDI from dermal
      exposure. For each non-cancer endpoint, the toxicity benchmark was divided by the
      calculated exposure to determine the margin of safety (MOS), which ranged from
      200 (respiratory tract) to 3*10(6) (irritation). Although available data indicate
      TDI is not carcinogenic, a theoretical excess cancer risk (1*10(-7)) was
      calculated. We conclude from this assessment that sleeping on a PU foam mattress
      does not pose TDI-related health risks to consumers.

PMID- 22871375
TI  - Versatility of the pedicled nasoseptal flap in the complicated basal skull
      fractures.
AB  - With the advancement of transnasal endoscopic technique, endoscopic repair of
      basal skull fractures has considerably substituted former external approaches.
      The endoscopically feasible pedicled flap, named nasoseptal flap has been
      extending its range of application, since it was introduced for the
      reconstruction of the defect after resection of skull base tumors. We introduce
      two patients with complicated basal skull fractures at different sites who were
      successfully treated by the transnasal endoscopic approach using nasoseptal flap.

PMID- 22871376
TI  - EGFR mutations and mucoepidermoid carcinoma: putative significance in differing
      populations.

PMID- 22871377
TI  - Effect of surface pore structure of nerve guide conduit on peripheral nerve
      regeneration.
AB  - Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different
      surface pore structures (nano-porous inner surface vs. micro-porous inner
      surface) but similar physical and chemical properties were fabricated by rolling
      the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the
      pore structure on peripheral nerve regeneration through the NGCs was investigated
      using a sciatic nerve defect model of rats. The nerve fibers and tissues were
      shown to have regenerated along the longitudinal direction through the NGC with a
      nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall
      of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their
      growth was restricted when compared with the Nanopore NGC, as investigated by
      immunohistochemical evaluations (by fluorescence microscopy with anti
      neurofilament staining and Hoechst staining for growth pattern of nerve fibers),
      histological evaluations (by light microscopy with Meyer's modified trichrome
      staining and Toluidine blue staining and transmission electron microscopy for the
      regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for
      reconnection between proximal and distal stumps). The effect of nerve growth
      factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration
      was not so significant when compared with NGCs not containing immobilized NGF.
      The NGC system with different surface pore structures but the same
      chemical/physical properties seems to be a good tool that is used for elucidating
      the surface pore effect of NGCs on nerve regeneration.

PMID- 22871378
TI  - Greening vacant lots to reduce violent crime: a randomised controlled trial.
AB  - BACKGROUND: Vacant lots are often overgrown with unwanted vegetation and filled
      with trash, making them attractive places to hide illegal guns, conduct illegal
      activities such as drug sales and prostitution, and engage in violent crime.
      There is some evidence that greening vacant lots is associated with reductions in
      violent crime. METHODS: We performed a randomised controlled trial of vacant lot
      greening to test the impact of this intervention on police reported crime and
      residents' perceptions of safety and disorder. Greening consisted of cleaning the
      lots, planting grass and trees, and building a wooden fence around the perimeter.
      We randomly allocated two vacant lot clusters to the greening intervention or to
      the control status (no intervention). Administrative data were used to determine
      crime rates, and local resident interviews at baseline (n=29) and at follow-up
      (n=21) were used to assess perceptions of safety and disorder. RESULTS:
      Unadjusted difference-in-differences estimates showed a non-significant decrease
      in the number of total crimes and gun assaults around greened vacant lots
      compared with control. People around the intervention vacant lots reported
      feeling significantly safer after greening compared with those living around
      control vacant lots (p<0.01). CONCLUSIONS: In this study, greening was associated
      with reductions in certain gun crimes and improvements in residents' perceptions
      of safety. A larger randomised controlled trial is needed to further investigate
      the link between vacant lot greening and violence reduction.

PMID- 22871379
TI  - Magnetic retrieval of ionic liquids: fast dispersive liquid-liquid
      microextraction for the determination of benzoylurea insecticides in
      environmental water samples.
AB  - A novel, rapid ionic liquid dispersive liquid-liquid microextraction (IL-DLLME)
      technique combined with magnetic retrieval (MR-IL-DLLME) has been developed and
      used to analyze five benzoylurea insecticides (BUs) in environmental water
      samples. This procedure was based on the magnetic retrieval of the ionic liquid
      using unmodified magnetic nanoparticles (MNPs). In this experiment, the fine
      ionic liquid droplets formed in aqueous samples functioned as an extractant for
      the extraction of BUs; after the extraction process was completed, Fe3O4 MNPs
      were added as a carrier to retrieve and separate the ionic liquid from the sample
      solution. After the supernatant was removed, the ionic liquid was desorbed using
      acetonitrile and subsequently injected directly into an HPLC system for analysis.
      The optimum experimental parameters are as follows: 20 mg of Fe3O4 (20 nm) as
      magnetic sorbents; 70 MUL of [C6MIM][PF6] as the extraction solvent; 300 MUL of
      acetonitrile as the disperser solvent; a vortex extraction time of 90 s with the
      vortex agitator set at 2800 rpm and no ionic strength. Under the optimized
      conditions, good linearity was obtained with correlation coefficients (r) greater
      than 0.9981. The repeatability and reproducibility of the proposed method were
      found to be good, and the limits of detection ranged from 0.05 MUg L-1 to 0.15
      MUg L-1. The proposed method was then successfully used for the rapid
      determination of BUs in real water samples. The recoveries of five BUs at two
      spiked levels ranged from 79.8 to 91.7% with RSDs less than 6.0%.

PMID- 22871380
TI  - Hydrophilic immobilized trypsin reactor with magnetic graphene oxide as support
      for high efficient proteome digestion.
AB  - In this paper, magnetic Fe3O4 nanoparticles modified graphene oxide
      nanocomposites (GO-CO-NH-Fe3O4) were prepared by covalent bonding, via the
      reaction between the amino groups of fuctionalized Fe3O4 and the carboxylic
      groups of GO, confirmed by Fourier-transform infrared spectra, Raman
      spectroscopy, and transmission electron microscopy. With GO-CO-NH-Fe3O4 as a
      novel substrate, trypsin was immobilized via pi-pi stacking and hydrogen bonding
      interaction, and the binding capacity of trypsin reached as high as 0.275 mg/mg.
      Since GO-CO-NH-Fe3O4 worked as not only support for enzyme immobilization, but
      also as an excellent microwave irradiation absorber, the digestion efficiency
      could be further improved with microwave assistance. By such an immobilized
      enzymatic reactor (IMER), standard proteins could be efficiently digested within
      15 s, with sequence coverages comparable or better than those obtained by
      conventional in-solution digestion (12 h). Since trypsin was immobilized under
      mild conditions, the enzymatic activity of IMER preserved at least for a month.
      In addition, due to the good hydrophilicity of GO, no peptide residue was
      observed in the sequent digestion of bovine serum albumin and myoglobin. To
      further confirm the efficiency of such an IMER for proteome analysis, it was
      applied to digest proteins extracted from rat liver, followed by nanoRPLC-ESI
      MS/MS analysis. With only 5 min microwave-assisted digestion, in 3 parallel runs,
      totally 456 protein groups were identified, comparable to that obtained by 12 h
      in-solution digestion, indicating the great potential of IMERs with GO-CO-NH
      Fe3O4 as the support for high throughput proteome study.

PMID- 22871381
TI  - Thrombolytic therapy in total mismatch with severe stroke after acute MCA
      occlusion and negative DWI.

PMID- 22871382
TI  - Interhemispheric approach to tumors of the posterior gyrus cinguli.
AB  - OBJECTIVE: Posterior gyrus cinguli tumors are a well-defined group of tumors that
      pose considerable challenges in creating surgical access and manipulating
      adjacent eloquent areas (visual and motor). Here we report our 5-year experience
      in the surgical treatment of these tumors and describe tumor characteristics,
      surgical steps, critical aspects, and prognostic factors. METHODS: This series
      comprises 37 patients operated on for glioma (high-grade in 28, low-grade in 9),
      often presenting with motor impairment (n=20), intracranial hypertension (n=15),
      seizures (n=11), and/or hemianopia (n=9). Preoperative assessment was performed
      with magnetic resonance imaging. Half of the tumors were more than 4 cm in size,
      and the majority presented secondary extension into the fronto-parieto-occipital
      area, the temporo-mesial area, and/or the corpus callosum. Positioning and
      assisted surgery were optimized in each patient based on preoperative planning.
      RESULTS: The ipsilateral interhemispheric approach was elected in all cases.
      Tumor size and extension were significantly associated with the degree of tumor
      removal. Total removal was achieved in 25 patients (65%); 4 (10%) had persistent
      morbidity (visual or motor deficits). The occurrence of local and systemic
      complications was negligible. CONCLUSIONS: Surgical treatment of posterior gyrus
      cinguli tumors can be safely approached via the interhemispheric route as it
      permits several beneficial operative maneuvers in selected cases.

PMID- 22871383
TI  - Reduced step length, not step length variability is central to gait hypokinesia
      in people with Parkinson's disease.
AB  - OBJECTIVES: Previous studies found that people with Parkinson's disease (PD)
      walked at a slower speed and with significantly shorter stride length and/or
      increase in variability of stride length than control subjects. The present study
      aimed to examine whether difference existed in amplitude and variability of step
      length between control and PD subjects if they walked at a similar speed.
      METHODS: This was a cross-sectional study. Thirteen PD patients and 15 healthy
      control subjects were instructed to walk at a similar speed on a treadmill under
      2 randomized conditions: walking alone (Walk(o)) and walking with digit
      subtraction of 3 (Walk(calculation)). Amplitude of step length (cm), variability
      of step length (%), and percent accuracy of the calculation task (%) were
      recorded and analysed. RESULTS: During both Walk(o) and Walk(calculation), PD
      patients had significantly shorter step length and larger step length variability
      than control subjects (p<0.05). When a cognitive task was added to walking, PD
      patients showed a significant decrease in step length without further change in
      step length variability (p<0.05). CONCLUSION: As reduced step length persisted
      when the control subjects walked at a speed similar to that of patients, our
      finding suggests that PD patients had a fundamental problem in regulating the
      amplitude of step length during walking.

PMID- 22871384
TI  - Quantitative analyses of bone composition in acetylcholine receptor M3R and
      alpha7 knockout mice.
AB  - AIMS: Increasing collagen synthesis was observed in lung after stimulation of
      nicotinic and muscarinic acetylcholine receptors (nAChR and mAChR) on
      fibroblasts. Since collagen synthesis is an important process during fracture
      healing and bone remodelling, we asked whether cholinergic receptors are involved
      in bone collagen production. MAIN METHODS: In the present study we analysed 16
      week old male knockout mice for nAChRalpha7 (alpha7-KO) and mAChR M3R (M3R-KO) in
      correlation to their corresponding wild types (WT). Microarchitecture of right
      femora, vertebrae Th13 and L1 were analysed by 3D Micro-CT, left femora by a
      three-point bending test and humeri by real-time RT-PCR. KEY FINDINGS: A
      significant decrease in relative bone volume, trabecular thickness, trabecular
      number, bone surface density, and a significant increase in trabecular separation
      and structure model index were measured for the M3R-KO using Micro-CT analysis.
      Bending stiffness of M3R-KO was significantly reduced in comparison to WT as well
      as the collagen 1alpha1 and 1alpha2 mRNA expression was down-regulated. No
      changes were detected for alpha7-KO using Micro-CT, biomechanical testing, and
      collagen mRNA expression. SIGNIFICANCE: Our results indicate that nAChRalpha7 are
      not involved in the regulation of bone collagen synthesis whereas M3R exert
      stimulatory effects on cancellous bone microarchitecture, flexural rigidity, and
      bone matrix synthesis. Since the M3R-KO exhibit bone structures similar to
      systemically diseased bone it might be valuable to establish new therapeutic
      strategies using administration of agonists for the M3R to improve bone
      qualities.

PMID- 22871385
TI  - Effect of (E)-2-(3,4-dimethoxyphenyl)-4-oxo-4H-chromen-7-yl-3-(3,4
      dimethoxyphenyl) acrylate on the development of atopic dermatitis-like lesions.
AB  - AIMS: In this study, we synthesized a novel chemical, (E)-2-(3,4-dimethoxyphenyl)
      4-oxo-4H-chromen-7-yl-3-(3,4-dimethoxyphenyl) acrylate (CSH) and investigated the
      effect of CSH on atopic dermatitis (AD) by evaluating the anti-inflammatory
      effect of CSH on immune cells in vitro and on atopic dermatitis-like lesions in
      vivo. MAIN METHODS: Human monocytic THP-1 cells and human eosinophilic EoL-1
      cells were treated with house dust mite extract in the absence and presence of
      CSH. Nc/Nga mice were sensitized to 2,4-dinitrochlorobenzne (DNCB) for 5 weeks
      and then orally and dorsally administered with CSH or dexamethasone for 3 weeks.
      KEY FINDINGS: CSH inhibited the secretion of monocyte chemotactic protein-1 (MCP
      1), interleukin (IL)-6 and IL-8 due to house dust mite extract in THP-1 cells.
      CSH also suppressed the secretion of MCP-1 and IL-8 in EoL-1 cells. In vivo, the
      skin severity score decreased after CSH treatment as compared to the control
      group. CSH suppressed the inflammatory cell infiltration into the dermis and
      thickened the epidermis. CSH reduced serum IgE level as compared to the control
      group. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased
      after treatment with concanavalin A and the increase of the cytokines was
      decreased by pre-treatment with CSH. The inhibitory effects of CSH on atopic
      lesions of DNCB-treated Nc/Nga mice were similar to those of dexamethasone,
      despite differing degrees depending on results evaluated in this study.
      SIGNIFICANCE: These results may contribute to the development of a therapeutic
      drug for the treatment of AD.

PMID- 22871386
TI  - TRPM7 is required for breast tumor cell metastasis.
AB  - TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity.
      TRPM7 has been implicated in control of cell adhesion and migration, but whether
      TRPM7 activity contributes to cancer progression has not been established. Here
      we report that high levels of TRPM7 expression independently predict poor outcome
      in breast cancer patients and that it is functionally required for metastasis
      formation in a mouse xenograft model of human breast cancer. Mechanistic
      investigation revealed that TRPM7 regulated myosin II-based cellular tension,
      thereby modifying focal adhesion number, cell-cell adhesion and polarized cell
      movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory
      complex adopted by cancer cells to drive metastasis formation.

PMID- 22871387
TI  - Brustle v Greenpeace, embryonic stem cell research and the European Court of
      Justice's new found morality.

PMID- 22871388
TI  - Quantification of blood flow and volume in arterioles and venules of the rat
      cerebral cortex using functional micro-ultrasound.
AB  - Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and
      blood flow speed are key parameters that characterize cerebral hemodynamics. We
      used contrast-enhanced functional micro-ultrasound (fMUS) imaging employing a
      disruption-replenishment imaging sequence to quantify these hemodynamic
      parameters in the anesthetized rat brain. The method has a spatial resolution of
      about 100 MUm in-plane and around 600 MUm through-plane, which is comparable to
      fMRI, and it has a superior temporal resolution of 40 ms per frame. We found no
      significant difference in rCBV of cortical and subcortical gray matter (0.89 +/-
      0.08 and 0.61 +/- 0.09 times the brain-average value, respectively). The rCBV was
      significantly higher in the vascular regions on the pial surface (3.89 +/- 0.71)
      and in the area of major vessels in the subcortical gray matter (2.02 +/- 0.31).
      Parametric images of rCBV, rCBF, and blood flow speed demonstrate spatial
      heterogeneity of these parameters on the 100 MUm scale. Segmentation of the
      cortex in arteriolar and venular-dominated regions identified through color
      Doppler imaging showed that rCBV is higher and flow speed is lower in venules
      than in arterioles. Finally, we show that the dependence of rCBV on rCBF was
      significantly different in cortical versus subcortical gray matter: the exponent
      alpha in the power law relation rCBV=s.rCBF(alpha) was 0.37 +/- 0.13 in cortical
      and 0.75 +/- 0.16 in subcortical gray matter. This work demonstrates that
      functional micro-ultrasound imaging affords quantification of hemodynamic
      parameters in the anesthetized rodent brain. This modality is a promising tool
      for neuroscientists studying these parameters in rodent models of diseases with a
      cerebrovascular component, such as stroke, neurodegeneration, and venous
      collagenosis. It is of particular import for studying conditions that selectively
      affect arteriolar versus venular compartments.

PMID- 22871389
TI  - Anaphylaxis during pregnancy.
AB  - Anaphylaxis during pregnancy, labor, and delivery can be catastrophic for the
      mother and, especially, the infant. Symptoms and signs can include intense vulvar
      and vaginal itching, low back pain, uterine cramps, fetal distress, and preterm
      labor. During the first 3 trimesters, etiologies are similar to those in
      nonpregnant women. During labor and delivery, common etiologies are beta-lactam
      antibiotics, natural rubber latex, and other agents used in medical and
      perioperative settings. Important caveats in management include injecting
      epinephrine (adrenaline) promptly, providing high-flow supplemental oxygen,
      positioning the mother on her left side to improve venous return to the heart,
      maintaining a minimum maternal systolic blood pressure of 90 mm Hg to ensure
      adequate placental perfusion, and continuous electronic monitoring.
      Cardiopulmonary resuscitation and emergency cesarean delivery should be performed
      when indicated. In all women of child-bearing age, allergy/immunology specialists
      can help to prevent anaphylaxis in pregnancy through prepregnancy risk assessment
      and risk reduction strategies, such as confirming the etiology of systemic
      allergic reactions, providing written instructions for allergen avoidance, and
      initiating relevant immune modulation. In pregnant women the benefits versus
      risks of skin tests, challenge tests, desensitization, and initiation of
      immunotherapy with allergens should be carefully weighed; if possible, these
      procedures should be deferred until after parturition. Prospective
      interdisciplinary studies of anaphylaxis during pregnancy are needed.

PMID- 22871390
TI  - Neural responses to emotional stimuli in comorbid borderline personality disorder
      and bipolar depression.
AB  - Borderline personality disorder (BPD) is a severe clinical condition
      characterised by different maladaptive traits such as impulsivity and affective
      lability. Mood and emotion dysregulation are core features of affective
      disorders. Indeed patients affected by mood disorder (MD) have a significantly
      higher prevalence of comorbid BPD, resulting in more unstable mood and poorer
      response to medication. Blood oxygen level-dependent functional magnetic
      resonance imaging has been used to investigate the neural correlates of emotional
      face processing. Images for each subject were entered into an analysis of
      variance (ANOVA) dividing participants into three group (MD, MD+BPD, Controls).
      MD+BPD patients show lower activations in the dorsolateral prefrontal cortex and
      higher activations in the cingulate cortex and hippocampus. The present study
      identifies the neural basis of the interaction between BPD and MD. The lower rate
      of response to treatment in MD+BPD could be related to a more severe emotional
      dysregulation syndrome.

PMID- 22871391
TI  - Efficacy and safety of add-on levetiracetam in refractory childhood epilepsy.
AB  - PURPOSE: The purpose of the present study was to evaluate the efficacy and safety
      of levetiracetam (LEV) in refractory epileptic children. METHODS: The study group
      included 61 outpatients (7 generalized, 48 localization-related, 3 undetermined,
      3 unclassified) aged between 16 months and 18 years. LEV was given twice daily at
      a total dose of 10 mg/kg/day. The final mean dose was 50.7 mg/kg/day. The mean
      number of prior anti-epileptic drugs was 5.2. The entire treatment period was
      more than 6 months after LEV administration. RESULTS: Fifteen children (24.6%)
      became seizure-free for 6 months after starting LEV, and 18 (29.5%) had a seizure
      reduction of more than 50% for the entire 6 months. The response rate was 33/61
      (54.1%). Responders included 2/3 of patients (66.7%) with epilepsy with
      continuous spikes and waves during slow sleep and 13/19 (68.4%) with frontal lobe
      epilepsy. The effective dosage of LEV in the responders demonstrated a wide range
      (mean, 46.1 mg/kg/day; range, 19.4-59.1 mg/kg/day), and showed bimodal
      distribution. Adverse events occurred in only two patients who did not require
      LEV discontinuation. CONCLUSION: LEV represents an important addition to the
      treatments available for refractory epileptic children.

PMID- 22871392
TI  - EEG findings in cooled asphyxiated newborns and correlation with site and
      severity of brain damage.
AB  - OBJECTIVE: EEG and MRI are useful tools to evaluate the severity of brain damage
      and to provide prognostic indications in asphyxiated neonates. Aim of our study
      is to analyze the relationship between serial neonatal EEGs and severity and
      sites of brain lesions on MRI in neonates undergoing hypothermia, following a
      hypoxic-ischemic injury. PATIENTS AND METHODS: Forty-eight term newborns
      underwent hypothermia. Serial videoEEG recordings were taken at 6, 24, 48 and 72
      h and during 2nd week of life. Brain MRI was performed at the end of 2nd
      postnatal week and correlated with EEG. RESULTS: EEGs improved during the first
      days. At the first recording 25 infants showed a severe or very low amplitude EEG
      pattern while at the 2nd week only 7 showed such patterns. As regards MRI, 21
      infants showed a predominant Basal Ganglia and Thalami damage, 4 infants showed a
      predominant focal Thalami lesion and 23 showed normal imaging or just mild White
      Matter abnormalities. Severity of EEG pattern was associated with the odds of
      having MRI lesions at Basal Ganglia, Thalami, White Matter, Internal Capsule, but
      not at Cortex. Infants who showed only mild EEG abnormalities in the first 2 days
      had no Basal Ganglia and Thalami MRI lesion. The persistence of a discontinuous
      EEG at the 2nd week recording is always associated with Basal Ganglia and Thalami
      damage. CONCLUSION: The severity of EEG background is associated with severity
      and site of MRI lesion pattern in neonates treated with hypothermia because of
      hypoxic-ischemic encephalopathy.

PMID- 22871394
TI  - Minor outbreak of extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae in an intensive care unit due to a contaminated sink.
AB  - During a period of seven months four patients on the neurosurgical intensive care
      unit at a tertiary care hospital in Sweden became infected or colonized by an
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The
      investigation revealed that the source of the outbreak was a contaminated sink.
      By replacing the sink and its plumbing and improving routines regarding sink
      practices, the outbreak was successfully controlled.

PMID- 22871393
TI  - Emotional response inhibition in bipolar disorder: a functional magnetic
      resonance imaging study of trait- and state-related abnormalities.
AB  - BACKGROUND: Impaired response inhibition and poor impulse control are hallmarks
      of the manic phase of bipolar disorder but are also present during depressive
      and, to a lesser degree, euthymic periods. The neural mechanisms underlying these
      impairments are poorly understood, including how mechanisms are related to
      bipolar trait or state effects. METHODS: One-hundred four unmedicated
      participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30),
      bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent
      functional magnetic resonance imaging during emotional and nonemotional go/no-go
      tasks. The go/no-go task requires participants to press a button for go stimuli,
      while inhibiting the response to no-go trials. In separate blocks, participants
      inhibited the response to happy faces, sad faces, or letters. RESULTS: The BE
      group had higher insula activity during happy face inhibition and greater
      activity in left inferior frontal gyrus during sad face inhibition, demonstrating
      bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated
      lower insula activity during inhibition of happy faces, though the depressed
      sample had lower activity than manic patients. The BD and BM groups had a greater
      response to inhibiting sad faces in emotion processing and regulation regions,
      including putamen, insula, and lateral prefrontal cortex. The manic group also
      had higher activity in insula and putamen during neutral letter inhibition.
      CONCLUSIONS: These results suggest distinct trait- and state-related neural
      abnormalities during response inhibition in bipolar disorder, with implications
      for future research and treatment.

PMID- 22871395
TI  - Purification of chicken breast protein hydrolysate and analysis of its
      antioxidant activity.
AB  - Chicken breast protein was hydrolyzed by papain under optimal conditions. The
      antioxidant activity of the chicken breast protein hydrolysate was then evaluated
      in vitro and in vivo using different measurements, including reducing power and
      DPPH radical scavenging assays. The reducing power of the hydrolysate was 0.5 at
      2.37 mg/mL. The DPPH radical scavenging assay showed that the EC50 value of the
      hydrolysate was 1.28 mg/mL. In antioxidant assays in vivo, d-galactose-induced
      aging mice administrated the fraction peptides of chicken breast protein
      hydrolysate showed significantly increased antioxidant enzyme activities, while
      malondialdehyde levels decreased both in serums and livers. Under a transmission
      electron microscope (TEM), the ultramicrostructure of hepatic tissue was observed
      and we found that the hydrolysate may play a part in inhibiting oxidative stress
      in hepatocytes in vivo. Therefore, we concluded that chicken breast protein
      hydrolysate exhibits significant antioxidant activity.

PMID- 22871396
TI  - Antitumor and antimetastatic activities of grape skin polyphenols in a murine
      model of breast cancer.
AB  - Treatment modalities are not effective once breast cancer metastasis has
      occurred. Dietary botanicals may have a better protective effect. We therefore
      investigated the effects of grape skin polyphenols on a highly metastatic mouse
      mammary carcinoma cell line. In vitro treatment of 4T1 cells, with grape skin
      polyphenols resulted in inhibition of the migration and viability in a dose
      dependent manner. The migration of 4T1 cells was significantly inhibited by grape
      skin polyphenols, even at a very low concentration (5 MUg/ml), and was totally
      inhibited when the concentration was 20 MUg/ml. However, 20 MUg/ml of grape skin
      polyphenols inhibited cell viability by only 11.4%. The inhibition of migration
      is independent of decreased cell viability or apoptosis induction. Further
      analysis indicated that the inhibition of migration by grape skin polyphenols is
      involved in blocking the PI3k/Akt and MAPK pathways. The effects of dietary grape
      skin polyphenols were then examined using an in vivo model in which 4T1 cells
      were implanted subcutaneously in Balb/c mice. The metastasis of tumor cells to
      the lungs was inhibited significantly by dietary grape skin extracts (0.5 and 1.0
      mg/ml in drinking water) and the survival of the mice enhanced. These data
      suggest that grape skin polyphenols possess chemotherapeutic efficacy against
      breast cancer with metastases.

PMID- 22871398
TI  - Effectiveness of an automated surveillance system for intensive care unit
      acquired infections.
AB  - This study assessed the effectiveness of a fully automated surveillance system
      for the detection of healthcare-associated infections (HCAIs) in intensive care
      units. Manual ward surveillance (MS) and electronic surveillance (ES) were
      performed for two intensive care units of the Vienna General Hospital. All
      patients admitted for a period longer than 48 h between 13 November 2006 and 7
      February 2007 were evaluated according to HELICS-defined rules for HCAI. The
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and personnel time spent per surveillance type were calculated.
      Ninety-three patient admissions were observed, whereby 30 HCAI episodes were
      taken as a reference standard. Results with MS versus ES were: sensitivity 40%
      versus 87%, specificity 94% versus 99%, PPV 71% versus 96%, NPV 80% versus 95%,
      and time spent per surveillance type 82.5 h versus 12.5 h. In conclusion, ES was
      found to be more effective than MS while consuming fewer personnel resources.

PMID- 22871397
TI  - A secure distributed logistic regression protocol for the detection of rare
      adverse drug events.
AB  - BACKGROUND: There is limited capacity to assess the comparative risks of
      medications after they enter the market. For rare adverse events, the pooling of
      data from multiple sources is necessary to have the power and sufficient
      population heterogeneity to detect differences in safety and effectiveness in
      genetic, ethnic and clinically defined subpopulations. However, combining
      datasets from different data custodians or jurisdictions to perform an analysis
      on the pooled data creates significant privacy concerns that would need to be
      addressed. Existing protocols for addressing these concerns can result in reduced
      analysis accuracy and can allow sensitive information to leak. OBJECTIVE: To
      develop a secure distributed multi-party computation protocol for logistic
      regression that provides strong privacy guarantees. METHODS: We developed a
      secure distributed logistic regression protocol using a single analysis center
      with multiple sites providing data. A theoretical security analysis demonstrates
      that the protocol is robust to plausible collusion attacks and does not allow the
      parties to gain new information from the data that are exchanged among them. The
      computational performance and accuracy of the protocol were evaluated on
      simulated datasets. RESULTS: The computational performance scales linearly as the
      dataset sizes increase. The addition of sites results in an exponential growth in
      computation time. However, for up to five sites, the time is still short and
      would not affect practical applications. The model parameters are the same as the
      results on pooled raw data analyzed in SAS, demonstrating high model accuracy.
      CONCLUSION: The proposed protocol and prototype system would allow the
      development of logistic regression models in a secure manner without requiring
      the sharing of personal health information. This can alleviate one of the key
      barriers to the establishment of large-scale post-marketing surveillance
      programs. We extended the secure protocol to account for correlations among
      patients within sites through generalized estimating equations, and to
      accommodate other link functions by extending it to generalized linear models.

PMID- 22871399
TI  - Phylogeny and colonization history of Pringlea antiscorbutica (Brassicaceae), an
      emblematic endemic from the South Indian Ocean Province.
AB  - The origins and evolution of sub-Antarctic island floras are not well understood.
      In particular there is uncertainty about the ages of the contemporary floras and
      the ultimate origins of the lineages they contain. Pringlea R. Br. (Brassicaceae)
      is a monotypic genus endemic to four sub-Antarctic island groups in the southern
      Indian Ocean. Here we used sequences from both the chloroplast and nuclear
      genomes to examine the phylogenetic position of this enigmatic genus. Our
      analyses confirm that Pringlea falls within the tribe Thelypodieae and provide a
      preliminary view of its relationships within the group. Divergence time estimates
      and ancestral area reconstructions imply Pringlea diverged from a South American
      ancestor ~5 Myr ago. It remains unclear whether the ancestor of Pringlea
      dispersed directly to the South Indian Ocean Province (SIOP) or used Antarctica
      as a stepping-stone; what is clear, however, is that following arrival in the
      SIOP several additional long-distance dispersal events must be inferred to
      explain the current distribution of this species. Our analyses also suggest that
      although Pringlea is likely to have inherited cold tolerance from its closest
      relatives, the distinctive morphology of this species evolved only after it split
      from the South American lineage. More generally, our results lend support to the
      hypothesis that angiosperms persisted on the sub-Antarctic islands throughout the
      Pliocene and Pleistocene. Taken together with evidence from other sub-Antarctic
      island plant groups, they suggest the extant flora of sub-Antarctic is likely to
      have been assembled over a broad time period and from lineages with distinctive
      biogeographic histories.

PMID- 22871400
TI  - The debate of dopamine's clinical application.

PMID- 22871401
TI  - [The first-line rescue system of medical support for manned aerospace flights
      project].

PMID- 22871402
TI  - [ATP-sensitive potassium channel involved in modulation of nitride oxide
      regulating contractile activity of isolated lymphatics from hemorrhagic shock
      rats].
AB  - OBJECTIVE: To investigate the mechanism of ATP-sensitive potassium channel
      (K(ATP)) on nitride oxide (NO) regulating contractile activity of isolated
      lymphatics from hemorrhagic shock (HS) rats. METHODS: Eighty - four Wistar rats
      were randomly divided into control group (n=6), HS 0.5-hour group (n=36), HS 2
      hour group (n=42). A segment of thoracic duct of rats was adopted for isolated
      lymphatics after HS, then the HS 0.5-hour and 2-hour lymphatics were incubated
      combined or respectively with K(ATP) inhibitor glibenclamide (Gli), opener of
      K(ATP) pinacidil (Pin), NO donor L-arginine (L-Arg), protein kinase A (PKA)
      inhibitor H-89, PKA donor 8-bromine-cyclic adenosine monophosphate (8-Br-cAMP),
      nitricoxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME),
      soluble guanylyl cyclase (sGC) inhibitor 1 h-[1,2,4]-oxadiazole-[4,3-a]-
      quinoxalin-1-one (ODQ), protein kinase G (PKG) inhibitor KT-5823 (named as HS 0.5
      h, HS 0.5 h + L-Arg, HS 0.5 h + L-Arg + H-89, HS 0.5 h + L-Arg + Gli, HS 0.5 h +
      8-Br-cAMP, HS 0.5 h + 8-Br-cAMP + Gli and HS 2 h, HS 2 h + L-NAME, HS 2 h + L
      NAME + Pin, HS 2 h + ODQ, HS 2 h + ODQ + Pin, HS 2 h + KT-5823, HS 2 h + KT-5823
      + Pin, n=6). By lymphatic perfusion in vitro, contractile frequency (CF) was
      recorded, and contractile amplitude (CA), tonic index (TI) and fractional pump
      flow (FPF) were calculated. RESULTS: The results suggested that the CF, TI, FPF
      of HS 0.5-hour lymphatics were significantly increased compared with control
      group, and the CF, TI, FPF decreased significantly when incubated with L-Arg. H
      89 could deteriorate the decreased effect of L-Arg on CF and FPF, and Gli could
      deteriorate the decreased effect of L-Arg on FPF. When the HS 0.5-hour lymphatics
      incubated with 8-Br-cAMP, the CF and FPF were all decreased significantly, and
      when the HS 0.5-hour lymphatics incubated with 8-Br-cAMP and Gli, the CF was
      significantly higher than HS 0.5 h + 8-Br-cAMP group, and the TI and FPF
      decreased significantly compared with HS 0.5-hour group. The CF, FPF, TI of HS 2
      hour lymphatics were significantly decreased compared with control group. L-NAME
      could increase the CF, TI, FPF; ODQ could increase the CF, TI; KT-5823 could
      increase the CF and FPF; when incubated with Pin respectively, the CF and FPF
      when incubated with L-NAME were decreased, the CF, TI and FPF when incubated with
      ODQ were decreased, in addition, the CA was recovered as level of control group,
      the CF and FPF when incubated with KT-5823 were decreased. CONCLUSIONS: K(ATP)
      involved in NO modulating pumping function of isolated lymphatics of HS rats, and
      the effect may be relative to the signal pathway of NO-cAMP-PKA and NO-cGMP-PKG.

PMID- 22871403
TI  - [The influence of sex hormones on human leukocyte antigen-DR, soluble myeloid
      cell receptor-1 and prognosis in patients with severe intra-abdominal infection].
AB  - OBJECTIVE: To evaluate the influence of serum estradiol, prolactin and
      testosterone levels on human leukocyte antigen-DR (HLA-DR), soluble myeloid cell
      receptor-1 (sTREM-1) and prognosis in patients with severe abdominal infection,
      in order to evaluate the clinical value of the above-mentioned sex hormones.
      METHODS: From July 10, 2009 to February 9, 2010, 73 cases with severe intra
      abdominal infections hospitalized in surgical intensive care unit (ICU) of
      Tianjin Nankai Hospital were enrolled. Within 72 hours after enrollment, serum
      estradiol, prolactin and testosterone levels were detected by radioimmunoassay.
      Based on their levels, all the cases were divided into increased estradiol group
      (n=38) and non-increased estradiol group (n=35), increased prolactin group (n=28)
      and non-increased prolactin group (n=45), decreased testosterone group (n=33) and
      non-decreased testosterone group (n=40) respectively. In addition, HLA-DR (flow
      cytometry), as well as of sTREM-1 (enzyme linked immunosorbent assay), acute
      physiology and chronic health evaluation II (APACHEII) score, hospital days, the
      ICU length, hospital costs and 28 day mortality were recorded. RESULTS: Compared
      with non-increased estradiol group, HLA-DR in increased estradiol group decreased
      significantly [(61.22+/-22.39)% vs. (75.09+/-14.85)%], while sTREM-1 (ng/L)
      increased obviously (291.59+/-148.13 vs. 216.48+/-124.82), APACHEII score lowered
      dramatically (11.47+/-6.88 vs. 15.36+/-8.79), hospital costs (ten thousands)
      raised significantly (10.98+/-8.15 vs 6.25+/-3.51), ICU length (days) was much
      shorter (8.56+/-4.05 vs. 12.17+/-7.99), and 28 days mortality was significantly
      lowered (10.00% vs. 32.75%,P<0.05 or P<0.01). Compared with non-increased
      prolactin group, increased prolactin group had much lower HLA-DR levels [(61.19+/
      21.50)% vs. (72.02+/-18.49)%], higher sTREM-1 levels (307.92+/-173.93 vs.
      223.01+/-106.93), at the same time, their cost of hospitalization (7.75+/-3.52
      vs. 11.36+/-8.24) and ICU stay length (9.14+/-3.15 vs. 13.24+/-2.16) were
      significantly lower (all P<0.05). Compared with non-decreased testosterone group,
      HLA-DR in decreased testosterone group increased significantly [(74.69+/-14.72)%
      vs. (62.24+/-22.54)%], while sTREM-1 decreased obviously (208.77+/-77.80 vs.
      294.20+/-169.36), APACHEII score lowered dramatically (10.57+/-6.97 vs. 15.39+/
      9.46), hospital costs decreased significantly (7.67+/-3.81 vs. 11.19+/-8.05), and
      28 days mortality lowered significantly (0 vs. 30.14%, P<0.05 or P<0.01).
      CONCLUSIONS: In the early stage of severe intra-abdominal infection, estrogen,
      prolactin and testosterone levels had powerful influences on immune,
      inflammation, and prognosis, which may indicated a widespread clinical
      application.

PMID- 22871404
TI  - [The immunomodulatory effects of hypertonic saline on sepsis patients].
AB  - OBJECTIVE: To approach the immunomodulatory effects of hypertonic saline (HTS) on
      sepsis patients. METHODS: Twenty-four septic patients admitted to surgical
      intensive care unit (SICU) received 5% HTS for fluid  resuscitation were
      prospectively enrolled from January 2009 to September 2010. Blood samples were
      collected at 15 minutes before, and at 15 minutes and 6, 12, and 24 hours after
      HTS infusion, the ability of respiratory burst of polymorphonuclear neutrophils
      (PMN) and the surface expression of CD11b and L-selectin in fresh whole blood was
      evaluated with flow cytometer. The plasma was collected to determine the
      solubility intercellular adhesion molecule-1 (sICAM-1), solubility L-selectin (sL
      selectin), tumor necrosis factor-alpha(TNF-alpha) and interleukins (IL-6, IL
      1beta). RESULTS: The baseline before HTS infusion was set as 100. Six hours after
      HTS infusion, the ability of respiratory burst of PMN was significantly increased
      [(160.0+/-19.6)%] compared with the baseline (P<0.05), and then gradually
      recovered  to  normal  level. The  expression  of  CD11b  and  L-selectin  in 
      the  surface of PMN was reduced rapidly at 15 minutes after HTS infusion, and to
      nadir at 12 hours [(70.4+/-5.7)%, (70.6+/-8.1)%], and L-selectin recovered to the
      normal level at 24 hours. Within short-term of HTS infusion, plasma inflammatory
      factor TNF-alpha was significantly decreased, and sustained a low level until 12
      hours, and then gradually increased. There was no change in IL-1beta. IL-6 and
      sICAM-1 was gradually increased, and peaked at 24 hours and 12 hours
      respectively, and remained at a high level. sL-selectin  increased  shortly  at 
      15 minutes  after  HTS  infusion  compared  with  baseline, and  remained  the
      level to 12 hours, and recovered to baseline at 24 hours. CONCLUSIONS: Delayed
      administration of HTS may have an immunomodulatory effect on sepsis patients,
      which could inhibit the activation of PMN.

PMID- 22871405
TI  - [The predictor value of peripheral blood procalcitonin levels in the evaluation
      of prognosis of patients with septic shock].
AB  - OBJECTIVE: To investigate the predictor value of peripheral blood procalcitonin
      (PCT) levels in the evaluation of prognosis of patients with septic shock.
      METHODS: A prospective study was conducted. Eighty-four patients with septic
      shock in intensive care unit (ICU) of Beijing Shijitan Hospital Affiliated to
      Capital Medical University were enrolled from May, 2011 to January, 2012. Serum
      PCT levels were monitored, and the acute physiology and chronic health evaluation
      II (APACHEII) score, sequential organ failure assessment (SOFA) score were
      recorded at the 1st, 3rd, 5th, and 7th day after admission. According to the 28
      day outcome after admission to ICU, the patients with septic shock were divided
      into the survivor group and non-survivor group, dynamic changes in serum PCT
      levels were compared between two groups and correlation analysis was carried out
      on serum PCT levels and the APACHEII score, SOFA score. RESULTS: (1) There was no
      significant difference in serum PCT levels (MUg/L) at the 1st and 3rd day between
      survivor group (n=38) and non-survivor group (n=46), but the serum PCT levels at
      the 5th and 7th day in non-survivor group were significantly higher than that in
      survivor group (5 days: 8.79+/-2.38 vs. 2.38+/-0.88, 7 days: 12.57+/-3.29 vs.
      0.71+/-0.22, both P<0.05), and the drop of PCT concentrations were significant
      compared with survivor group (1.91+/-1.21 vs. 10.27+/-4.49, P<0.05). At the same
      time, positive statistical correlation was found between serum PCT levels and
      APACHEII score, SOFA score (5 days: R(APACHEII)=0.395, R(SOFA)=0.396; 7 days:
      R(APACHEII)=0.675, R(SOFA)=0.648, all P<0.01). (2) Receiver operator
      characteristic curve (ROC curve) of serum PCT levels on the 7th day could
      significantly predict the 28-day mortality, maximal area under the curve (AUC) of
      PCT was 0.886. When PCT was 0.965 MUg/L, the sensitivity and specificity were
      appropriate. By multivariate factors logistic regression, serum PCT
      concentrations were not significantly correlated with 28-day mortality. (3) The
      median survival time (days) of patients with 7-day PCT <1.0 MUg/L was far more
      than that of the patients with PCT>1.0 MUg/L (28.0 vs. 14.1, P<0.05).
      CONCLUSIONS: Dynamic monitoring of serum PCT levels can help to assessment the
      prognosis of septic shock and also in predicting the severity of the illness, but
      it may not be a significant independent prognostic marker for 28-day survival in
      the patients with septic shock.

PMID- 22871406
TI  - [Role of mesenteric lymph drainage improving the metabolism of red blood cell in
      hemorrhagic shock rats following fluid resuscitation].
AB  - OBJECTIVE: To observe the effects of mesenteric lymph drainage on the metabolism
      of red blood cell (RBC) in hemorrhagic shock (HS) rats following fluid
      resuscitation. METHODS: Eighteen male Wistar rats were randomly divided into sham
      group (n=6), HS group (n=6), HS + drainage group (n=6). After 1.5 hours of HS
      model prepared, the animals were given fluid resuscitation by lost blood plus 
      equal volume  of  Ringer  solution  within 30 minutes in HS and HS + drainage
      groups, and mesenteric lymph drainage was performed after 1 hour of hypotension
      in HS + drainage group. At 3 hours after resuscitation or corresponding time,
      blood samples were obtained from abdominal aorta. Membrane suspensions of RBC
      prepared from part of whole blood samples were used to measure the activities of
      adenosine triphosphate ase (ATPase) and contents of ATP and lactic acid (LA), the
      intracellular fluid of RBC prepared from part of whole blood samples was used to
      determine the concentration of 2,3-diphosphoglyceric acid (2,3-DPG), Na(+) and
      K(+), plasma samples isolated from blood by centrifugation were used to determine
      the concentration of Na(+), K(+), Cl(-) and total Ca. RESULTS: Compared with sham
      group, the content of ATP (MUmol/g), activity of Na(+)-K(+)-ATPase (MUmol*mg(
      1)*h(-1)) and Ca(2+)-ATPase (MUmol*mg(-1)*h(-1)) in RBC membrane and total Ca
      (mmol/L) in plasma were decreased markedly (ATP: 6.698+/-0.938 vs. 10.670+/
      1.466, Na(+)-K(+)-ATPase: 0.042+/-0.010 vs. 0.066+/-0.019, Ca(2+)-ATPase: 0.054+/
      0.015 vs. 0.081+/-0.017, total Ca: 2.27+/-0.18 vs. 2.66+/-0.21, P<0.05 or P<0.01)
      in HS group, and the content of LA (mmol/g) in RBC and K(+) (mmol/L), Cl(-)
      (mmol/L) in plasma were increased observably in HS group (LA: 3.472+/-0.853 vs.
      1.743+/-0.395, K(+): 5.83+/-0.34 vs. 5.23+/-0.37, Cl(-): 113.37+/-3.63 vs.
      106.35+/-4.99, P<0.05 or P<0.01), there was no significant difference in term of
      the contents of 2,3-DPG (mmol/L: 2.196+/-0.609 vs. 2.590+/-0.574, P>0.05).
      Compared with HS group, the contents of 2,3-DPG (4.459+/-0.900) and ATP (8.859+/
      1.189), the activities of Na(+)-K(+)-ATPase (0.089+/-0.022), Ca(2+)-ATPase
      (0.082+/-0.020) of RBC were increased in HS + drainage group, and the level of LA
      (2.060+/-0.810) was decreased observably (P<0.05 or P<0.01), there were no
      significant differences in the other indices. CONCLUSIONS: The results indicate
      that shock mesenteric lymph drainage plays an important role in improving the
      metabolism of RBC in HS rats following fluid resuscitation, subsequently, may
      preserve the structure and function of RBC.

PMID- 22871407
TI  - [Effect of resuscitation strategy based on the early goal directed therapy on the
      prognosis of patients with shock].
AB  - OBJECTIVE: To evaluate the effects of fluid management strategies in early goal
      directed therapy (EGDT) on the prognosis of patients with shock. METHODS:
      Clinical data of 79 patients with septic shock or hemorrhagic shock admitted to
      emergency intensive care unit (EICU) of the First People's Hospital of Yunnan
      Province were retrospectively analyzed. Patients were divided into continual
      fluid  administrating group (n=41) in accordance with protocol calculating
      approximating fluid volume and adjust the infusion speed based on blood pressure,
      heart rate, pulse saturation of blood oxygen (SpO(2)) and urine output with the
      end of fluid resuscitation was set to restore spontaneous circulation function
      and wean off vasoactive drugs, and the conservative fluid resuscitation group
      (n=38) by means of using vasoactive agents to maintenance blood pressure after
      infusing amount (20 ml/kg) of liquid early, respectively. The 28-day mortality
      and the time of using pressure agents were compared between two groups. According
      to the 28-day mortality, patients were further divided into the survival group
      (n=37) and death group (n=42), and acute physiology and chronic health evaluation
      II (APACHEII) score was compared between two groups. Logistic regression analysis
      of prognostic factors was conducted to identify and describe the relationship
      between the prognosis and fluid resuscitation methods and strategies. RESULTS:
      The 28-day mortality of continual fluid administrating group was significantly
      lower than that of the conservative fluid resuscitation group (14.63% vs. 94.74%,
      P<0.01), total drugs supporting time (hours) was significantly shorter than that
      in conservative fluid resuscitation group (33.24+/-17.56 vs. 58.29+/-34.78,
      P<0.05). Thirty-six cases of 42 death patients received conservative fluid
      resuscitation (85.7%), but 35 cases of 37 survival patients received continual
      fluid administration (94.6%). Logistic regression analysis showed that odds ratio
      (OR) of brain natriuretic peptide before death or shifted out ICU was 0.9136, 95%
      confidence interval (95%CI) was 0.8125  to  0.9986, regression  coefficient  was 
      0.0931, P=0.0478, OR of procalcitonin before death or shifted out ICU was 0.9095,
      95%CI was 0.8294 to 0.9973, regression coefficient was -0.0949, P=0.0436, and OR
      of blood lactate level before death or shifted out ICU was 0.5023, 95%CI was
      0.2833 to 0.8905, regression coefficient was -0.6885, P=0.0184. CONCLUSIONS:
      Ongoing fluid resuscitation early in accordance with method to theoretically
      calculate fluid volume and to adjust infusion speed based on blood pressure,
      heart rate, SpO(2) and urine, withdrawal of vasoactive drugs, the mortality of
      patients with shock was significantly reduced.

PMID- 22871408
TI  - [Evaluation of accuracy and influence factors of bedside blood glucose monitoring
      in critically ill patients].
AB  - OBJECTIVE: To evaluate the accuracy and influence factors of point-of-care
      testing (POCT) for glucose in critically ill patients. METHODS: Two hundred and
      forty critically ill patients aged >=18 years in department of critical care
      medicine were enrolled. According to blood glucose level (BGL) during glucose
      control, patients were divided into three groups: (1) hypoglycemia group, BGL<4.5
      mmol/L, n=32; (2) euglycemia group, BGL 4.5-8.3 mmol/L, n=138; (3) hyperglycemia
      group, BGL>8.3 mmol/L, n=70. The blood samples from vein, artery and capillary of
      patients were collected synchronically and the blood glucose of POCT were
      determined with glucose oxidase (GOD) and glucose dehydrogenase (GDH) methods,
      respectively, compared with blood glucose reference values of laboratory
      [hexokinase method (HK method)]. The accuracy of POCT for glucose and influence
      factors were analyzed statistically by the logistic regression method. RESULTS:
      (1) The inaccurate rates of glucose values in blood samples from vein, artery and
      capillary in hypoglycemia group (GDH method: 25.00%, 40.62%, 40.62%; GOD method:
      59.38%, 71.88%, 71.88%) were significantly higher than those in euglycemia group
      (GDH method: 2.90%, 9.42%, 7.97%; GOD method: 18.12%, 27.54%, 27.54%) and
      hyperglycemia group (GDH method: 1.43%, 8.57%, 4.28%; GOD method: 11.43%, 8.57%,
      11.43%, all P<0.01). (2) The average levels of difference for the glucose
      reference value of laboratory and the glucose value measured by glucometer in
      hypoglycemia group were 0.41-0.69 mmol/L (GDH method) and 0.92-1.18 mmol/L (GOD
      method), in euglycemia 0.16-0.33 mmol/L and 0.77-0.90 mmol/L, in hyperglycemia
      group -0.06-0.18 mmol/L and 0.56-0.76 mmol/L, respectively. (3) The correlation
      coefficients between the laboratory and glucometer in hypoglycemia group were
      respectively 0.812-0.853 (GDH method) and 0.723-0.816 (GOD method). The
      correlation coefficients in euglycemia group were 0.862-0.890 and 0.768-0.857.
      They were elevated to 0.922-0.957 and 0.896-0.922 in hyperglycemia group (all
      P<0.01). (4)On the influence factors of accuracy in POCT for glucose, BGL, acute
      physiology and chronic health evaluation II (APACHEII) score and hematocrit level
      were into the logistic regression equation. CONCLUSIONS: The accuracy of POCT for
      glucose was markedly affected by the BGL, severity of patients and hematocrit
      level during glucose control. Under hypoglycemia, the agreement between
      laboratory and glucometer measurements was obviously fallen and it tended to
      overestimate the patient's real glucose value.

PMID- 22871409
TI  - [The effects of activated protein C on the von Willebrand factor and von
      Willebrand factor cleaving protease of rat aortic endothelial cell induced by
      lipopolysaccharide].
AB  - OBJECTIVE: To investigate the activated protein C (APC) on the von Willebrand
      factor antigen (vWFAg) and von Willebrand factor cleaving protease (ADAMTS-13)
      protein expression in rat aortic endothelial cells (RAECs) induced by
      lipopolysaccharide (LPS). METHODS: RAECs from Wistar rats were cultured with the
      tissue explants adherence method. RAECs were cultured for one week, After one
      week culture, RAECs in 4-5 generations were divided into control group, LPS
      stimulation groups (1 mg/L) and APC intervention groups (0.1, 1 and 10 mg/L APC
      was added after LPS stimulation). The supernatants were obtained at 12, 24, 48,
      and 72 hours after LPS stimulated to determine the vWFAg and protein of ADAMTS-13
      expression by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: In the
      control group, RAECs expressed little vWFAg and protein of ADAMTS-13. With
      stimulation of LPS, the vWFAg was significantly increased at 12 hours, and
      reached the peak at 48 hours [(285.45+/-30.13)%], and the level of ADAMTS-13
      (MUg/L) was gradually decreased, and reached the nadir at 72 hours (13.32+/
      2.37), there was significant difference compared with control group [vWFAg:
      (94.53+/-7.83)%, ADAMTS-13: 115.76+/-2.36, both P<0.01). The effects on vWFAg
      promoting and ADAMTS-13 inhibition after LPS stimulation could be dose
      dependently reversed by APC. 10 mg/L of APC could decrease the peak of vWFAg at
      48 hours of LPS stimulation [(198.43+/-17.92)% vs. (285.45+/-30.13)%], and
      increase the minimize of ADAMTS-13 (MUg/L) at 72 hours of LPS stimulation
      (125.25+/-2.70 vs. 13.32+/-2.37), with significant difference (both P<0.01).
      CONCLUSIONS: After stimulation with LPS, the level of vWFAg was time-dependent
      increased, as the protein of ADAMTS-13 was decreased. APC could attenuate the
      effect of LPS on vWFAg and protein of ADAMTS-13 with dose-dependent and time
      dependent patterns.

PMID- 22871410
TI  - [Therapeutic effects of unfractionated heparin on lipopolysaccharide-activated
      matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in
      endothelial cells].
AB  - OBJECTIVE: To investigate the expressions of matrix metalloproteinase-9 and
      tissue inhibitors of metalloproteinase-1 (TIMP-1) in injured endothelial cells
      induced by lipopolysaccharide (LPS) and the effects of unfractionated heparin
      (UFH) on the level of expressions. METHODS: The human pulmonary microvascular
      endothelial cells (HPMECs) were injured by LPS (10 MUg/ml). In UFH pretreatment
      group, the cells were interfered with 0.1 U/ml or 1 U/ml UFH within 15 minutes
      before stimulus of LPS. In control group, the cells were cultured in equal volume
      of phosphate buffered saline (PBS). The RNA of the respectively cells were
      extracted at 2, 6, 12 hours after stimulus, and the expressions of MMP-9 mRNA and
      TIMP-1 mRNA were detected by real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). RESULTS: Compared with control group, the
      expressions of MMP-9 mRNA and TIMP-1 mRNA were increased after stimulation of
      LPS, and peaked at 12 hours (MMP-9 mRNA: 4.26+/-0.81 vs. 1.00+/-0.46, TIMP-1
      mRNA: 4.93+/-0.08 vs. 1.00+/-0.13, both P<0.05), the change in TIMP-1 was more
      significant. While as UFH pretreatment could significantly down-regulated the
      mRNA expressions of MMP-9 and TIMP-1 (UFH 0.1 U/ml group MMP-9 mRNA: 2.74+/-0.30,
      TIMP-1 mRNA: 2.96+/-0.13; UFH 1 U/ml group MMP-9 mRNA: 3.08+/-0.48, TIMP-1 mRNA:
      2.93+/-0.27, all P<0.05). There were no significant differences in mRNA
      expressions between two UFH groups. CONCLUSIONS: The expressions of MMP-9 and
      TIMP-1 of HPMEC injured by LPS were obviously increased, UFH might attenuate the
      injury via inhibiting the expressions of MMP-9 and TIMP-1.

PMID- 22871412
TI  - [Comparison between pulse-indicated continuous cardiac output catheter and Swan
      Ganz catheter in evaluating blood volume].

PMID- 22871411
TI  - [Survey of the occurrence and identification of delirium in the intensive care
      unit].

PMID- 22871413
TI  - [The prognostic value of extravascular lung water index on septic shock
      patients].

PMID- 22871414
TI  - Development of validated QSPR models for impact sensitivity of nitroaliphatic
      compounds.
AB  - The European regulation of chemicals named REACH implies the assessment of a
      large number of substances based on their hazardous properties. However, the
      complete characterization of physico-chemical, toxicological and eco
      toxicological properties by experimental means is incompatible with the imposed
      calendar of REACH. Hence, there is a real need in evaluating the capabilities of
      alternative methods such as quantitative structure-property relationship (QSPR)
      models, notably for physico-chemical properties. In the present work, the
      molecular structures of 50 itroaliphatic compounds were correlated with their
      impact sensitivities (h(50%)) using such predictive models. More than 400
      olecular descriptors (constitutional, topological, geometrical, quantum chemical)
      were calculated and linear and multi-linear regressions were performed to find
      accurate quantitative relationships with experimental impact sensitivities.
      Considering different sets of descriptors, four predictive models were obtained
      and two of them were selected for their predictive reliability. To our knowledge,
      these QSPR models for the impact sensitivity of nitroaliphatic compounds are the
      first ones being rigorously validated (both internally and externally) with
      defined applicability domains. They hence follow all OECD principles for
      regulatory acceptability of QSPRs, allowing possible application in REACH.

PMID- 22871415
TI  - Using S and Pb isotope ratios to trace leaching of toxic substances from an acid
      impacted industrial-waste landfill (Pozdatky, Czech Republic).
AB  - Slightly elevated concentrations of toxic species in waters sampled in the
      surroundings of a leaky landfill may be both a sign of an approaching contaminant
      plume, or a result of water-rock interaction. Isotopes can be instrumental in
      distinguishing between anthropogenic and geogenic species in groundwater. We
      studied sulfur and lead isotope ratios at an abandoned industrial-waste landfill,
      located in a densely populated part of Central Europe. Stable isotope variability
      in space and time was used to follow the movement of a groundwater plume,
      contaminated with toxic metals (Cd, Cr, Be), in fractured granitoids. Toxic
      metals had been mobilized from industrial waste by a strong pulse of sulfuric
      acid, also deposited in the landfill. Both tracers exhibited a wide range of
      values (delta(34)S between +2.6 and +18.90/00; (206)Pb/(207)Pb between 1.16 and
      1.39), which facilitated identification of mixing end-members, and made it
      possible to assess the sources of the studied species. In situ fractionations did
      not hinder source apportionment. Influx of contaminated groundwater was observed
      neither in irrigation wells in a nearby village, nor at distances greater than
      300 m from the landfill. Combination of stable isotope tracers can be used as
      part of an early-warning system in landscapes affected by landfills.

PMID- 22871416
TI  - Hydrocarbon removal from bilgewater by a combination of air-stripping and
      photocatalysis.
AB  - In order to prevent hydrocarbon discharge at sea from the bilge of ships, the
      International Maritime Organization (IMO) enacted the MARPOL 73/78 convention in
      which effluents are now limited to those with maximum oil content of 15 ppmv.
      Thus, photocatalysis and air-stripping were combined for the hydrocarbon removal
      from a real oily bilgewater sample and an original monitoring of both aqueous and
      gaseous phases was performed by GC/MS to better understand the process. Our
      results show that the hydrocarbon oil index [HC] can be reduced to its maximum
      permissible value of 15 ppmv (MARPOL) in only 8.5h when photocatalysis and air
      stripping are used together in a synergistic way, as against 17 h when
      photocatalysis is used alone. However, this air-assisted photocatalytic process
      emits a large quantity of volatile organic compounds (VOC) and, within the first
      four hours, ca. 10% of the hydrocarbon removal in the aqueous phase is actually
      just transferred into the gaseous one. Finally, we highlight that the n-alkanes
      with a number of carbon atoms higher than 15 (N(C)>15) are those which most
      decrease the rate of [HC] removal.

PMID- 22871417
TI  - The common marmoset as a novel animal model system for biomedical and
      neuroscience research applications.
AB  - The common marmoset (Callithrix jacchus), a small New World primate, has been
      attracting much attention in the research field of biomedical science and
      neuroscience, based on its (i) cross-reactivity with human cytokines or hormones,
      (ii) comparative ease in handling due to its small size, (iii) high reproductive
      efficiency, (iv) establishment of basic research tools, and (v) advantages of its
      unique behavioral and cognitive characters. Various neurological disease models
      have been developed in the common marmoset, including Parkinson's disease,
      Huntington's disease, Alzheimer's disease, stroke, multiple sclerosis and spinal
      cord injury. We recently developed transgenic common marmoset with germline
      transmission, which is expected to provide a new animal model for the study of
      human diseases. In this review, we summarize the recent progress of biomedical
      research and neuroscience using common marmoset as an excellent model system.

PMID- 22871418
TI  - Hand osteoarthritis: new insights.
AB  - Hand osteoarthritis (OA) is one of the most common localization of OA affecting
      predominantly women. The etiology seems to be multifactorial and the disease
      heterogeneous, comprising several clinical and radiological subsets. Hand OA
      includes thumb base (trapeziometarcarpal joint), metacarpophalangeal joints,
      distal and proximal interphalangeal joints OA. We reviewed below the prevalence,
      diagnosis, imaging, epidemiology, risk factors, but mostly the last discoveries
      in the biology and pathophysiology with particular attention to the potential
      role of adipokines and genetic factors. Finally, we also reviewed the different
      treatments currently available as well as potential future therapies.

PMID- 22871419
TI  - Re-designed N-terminus enhances expression, solubility and crystallizability of
      mitochondrial protein.
AB  - Mitochondrial aminoacyl-tRNA synthetases are key enzymes in translation. They are
      encoded by the nuclear genome, synthesized as precursors in the cytosol and
      imported. Most are matured by cleavage of their N-terminal targeting sequence.
      The poor expression of mature proteins in prokaryotic systems, along with their
      low solubility and stability after purification are major obstacles for
      biophysical and crystallographic studies. The purpose of the present work was to
      analyze the influence of additives on a slightly soluble aspartyl-tRNA synthetase
      and of the N-terminal sequence of the protein on its expression and solubility.
      On the one hand, the solubility of the enzyme was augmented to some extent in the
      presence of a chemical analog of the intermediary product aspartyl-adenylate, 5'
      O-[N-(L aspartyl) sulfamoyl] adenosine. On the other hand, expression was
      enhanced by extending the N-terminus by seven natural amino acids from the
      predicted targeting sequence. The re-designed enzyme was active, monodisperse,
      more soluble and yielded crystals that are suitable for structure determination.
      This result underlines the importance of the N-terminal residue sequence for
      solubility. It suggests that additional criteria should be taken into account for
      the prediction of cleavage sites in mitochondrial targeting sequences.

PMID- 22871420
TI  - A review of hospital characteristics associated with improved performance.
AB  - PURPOSE: The objective of this review was to critically appraise the literature
      relating to associations between high-level structural and operational hospital
      characteristics and improved performance. DATA SOURCES: The Cochrane Library,
      MEDLINE (Ovid), CINAHL, proQuest and PsychINFO were searched for articles
      published between January 1996 and May 2010. Reference lists of included articles
      were reviewed and key journals were hand searched for relevant articles. STUDY
      SELECTION: and data extraction Studies were included if they were systematic
      reviews or meta-analyses, randomized controlled trials, controlled before and
      after studies or observational studies (cohort and cross-sectional) that were
      multicentre, comparative performance studies. Two reviewers independently
      extracted data, assigned grades of evidence according to the Australian National
      Health and Medical Research Council guidelines and critically appraised the
      included articles. Data synthesis Fifty-seven studies were reported within 12
      systematic reviews and 47 observational articles. There was heterogeneity in use
      and definition of performance outcomes. Hospital characteristics investigated
      were environment (incentives, market characteristics), structure (network
      membership, ownership, teaching status, geographical setting, service size) and
      operational design (innovativeness, leadership, organizational culture, public
      reporting and patient safety practices, information technology systems and
      decision support, service activity and planning, workforce design, staff training
      and education). The strongest evidence for an association with overall
      performance was identified for computerized physician order entry systems. Some
      evidence supported the associations with workforce design, use of financial
      incentives, nursing leadership and hospital volume. CONCLUSION: There is limited,
      mainly low-quality evidence, supporting the associations between hospital
      characteristics and healthcare performance. Further characteristic-specific
      systematic reviews are indicated.

PMID- 22871422
TI  - WITHDRAWN: Sustained protection against photoreceptor degeneration in tubby mice
      by intravitreal injection of nanoceria.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22871421
TI  - Cystamine-terminated poly(beta-amino ester)s for siRNA delivery to human
      mesenchymal stem cells and enhancement of osteogenic differentiation.
AB  - Enhancing human mesenchymal stem cell (hMSC) differentiation via RNA interference
      (RNAi) could provide an effective way of controlling cell fate for tissue
      engineering, but a safe and effective delivery vehicle must first be developed.
      Here, we evaluated an array of synthetic end-modified poly(beta-amino ester)
      (PBAE)-based nanoparticles to optimize siRNA delivery into hMSCs. In general,
      cystamine-terminated polymers caused the most knockdown, with the best polymer
      achieving 91% knockdown 20 days post-transfection. Binding studies revealed that
      the cystamine-terminated polymer bound siRNA tightly at lower weight ratios of
      polymer to siRNA but then efficiently released siRNA upon exposure to a reducing
      environment, suggesting that this class of PBAEs can form tight initial
      interactions with its cargo and then cause efficient, environmentally-triggered
      release in the cytoplasm. Finally, we tested a functional application of this
      system by transfecting hMSCs with siRNA against an inhibitor of osteogenesis, B
      cell lymphoma (Bcl)-like protein 2 (BCL2L2). This resulted in enhanced
      osteogenesis over 4 weeks as evidenced by Alizarin Red S staining and calcium
      quantification. The bioreducible PBAE/siRNA nanoparticles developed here can
      provide a means of safe and effective control of hMSC differentiation for a wide
      variety of applications.

PMID- 22871423
TI  - Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide
      amine) micelles for co-delivery of drug and gene.
AB  - We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG3.5k-Paclitaxel
      (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly
      (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and
      drug. The APP polymer self-assembled into cationic polymeric micelles with a
      critical micelle concentration (CMC) value of approximately 0.062 mg/mL, which
      was determined from measurements of the UV absorption of pyrene. The micelles
      have an average size of about 3 nm and a zeta potential of about +14 mV. Due to
      the positive surface charge, APP micelles formed polyplexes with plasmid DNA
      approximately 200 nm in diameter. The luciferase gene and mouse interleukin-12
      (IL-12) gene was used to monitor gene delivery potency. APP polyplexes showed
      increased gene delivery efficiency and cellular uptake with higher anticancer
      potency than paclitaxel alone. These results demonstrate that an APP micelle
      based delivery system is well suitable for the co-delivery of gene and drug.

PMID- 22871424
TI  - A cyanine-based fluorescent sensor for detecting endogenous zinc ions in live
      cells and organisms.
AB  - The highly sensitive and selective, cyanine-based Zn(2+) fluorescent sensor CTMPA
      was designed, prepared and utilized to monitor endogenous zinc ions in live cells
      and organisms. Upon addition of Zn(2+) to solutions of CTMPA, an observable blue
      to light red color change occurs that can be monitored by using UV-vis
      spectroscopy. Concomitantly, a remarkably hypsochromic shift (ca.140 nm) in the
      emission maximum of CTMPA takes place from 730 nm to 590 nm. The observations
      indicate that association of the probe with Zn(2+) leads to shortening of the
      conjugated, pi-electron system in the cyanine dye, the phenomenon likely
      responsible for the large hypsochromic shift observed in emission spectra. Since
      CTMPA has meritorious features, including a large spectral shift induced by
      Zn(2+), a low fluorescence background and a high sensitivity toward Zn(2+), CTMPA
      was employed to monitor endogeneous zinc ions released during apoptosis and trace
      intact Zn(2+) during zebrafish development. Owing to its low background and high
      sensitivity, CTMPA serves as the first probe for fluorescence detection of
      neuromasts in zebrafish. The results obtained from experiments using live cells
      and organisms suggest that CTMPA will be a highly useful probe in zinc biology
      studies. The effort has demonstrated that a strategy, which relies on changes in
      the pi-electron conjugation length of cyanine molecules promoted by guest
      coordination, has great potential for the creation of cyanine-based probes.

PMID- 22871425
TI  - Nodular dermatofibrosis in a dog without a renal tumour or a mutation in the
      folliculin gene.
AB  - Canine nodular dermatofibrosis is a rare skin disease associated with renal
      cystadenoma or cystadenocarcinoma and uncommonly with uterine leiomyoma. It is
      generally seen in German shepherd dogs, but has been also reported in other
      breeds, and a relationship has been suggested with mutation of the gene encoding
      folliculin (FLCN), which is located on chromosome 5. A 10-year-old female golden
      retriever was presented because of numerous firm cutaneous nodules up to 4 cm in
      diameter over the entire body surface. Cytological and histopathological
      examinations confirmed generalized cutaneous nodular dermatofibrosis, but
      ultrasonography of both kidneys ruled out renal neoplasia. Ovariohysterectomy was
      performed because of prolonged oestrus periods. Microscopical examination of the
      excised tissues confirmed the absence of uterine neoplasia, but identified rete
      adenoma of the right ovary. Abdominal ultrasound performed repeatedly over a 5
      year follow-up period did not identify any alteration in the renal parenchyma.
      Molecular studies excluded the presence of any mutation in the FLCN gene.

PMID- 22871426
TI  - Monitoring the dissolution of Active Pharmaceutical Ingredient and TPGS in real
      time via IR spectroscopy during the manufacturing of liquid dosage formulation.
AB  - Infrared spectroscopy is used to monitor the dissolution of the Active
      Pharmaceutical Ingredient (API) and an excipient (vitamin E - TPGS) during
      manufacturing of a liquid pharmaceutical formulation. The goal of the analysis is
      to explore options for real-time, on screen, and quantitative monitoring of these
      two components by using an iC10 instrument. As is common, the first step in the
      approach is to create respective calibration models for the two components and
      then apply those models on the spectra obtained from scale-up batches.
      Interestingly, while the API dissolves at the room temperature, TPGS dissolves at
      an acceptable rate at 50  degrees C so both temperatures have to be considered.
      It is shown that univariate models of sufficient accuracy can be developed with a
      straightforward applicability to the scale-up batches spectra and providing
      reasonably accurate estimates of the API and TPGS concentrations. Some
      limitations of the software on the employed instrument may diminish the prospect
      for the quantitative analysis of the components of interest in this formulation.

PMID- 22871427
TI  - A method for simultaneous quantification of phospholipid species by routine 31P
      NMR.
AB  - We report a (31)P NMR assay for quantification of aqueous phospholipid samples.
      Using a capillary with trimethylphosphate as internal standard, the limit of
      quantification is 1.30 mM. Comparison of the (31)P NMR quantification method in
      aqueous buffer and in organic solvent revealed that the two methods are equal
      within experimental error. Changing the pH of the buffer enables peak separation
      for different phospholipid species. This is an advantage compared to the
      commercial enzyme assay based on phospholipase D and choline oxidase. The
      reported method, using routine (31)P NMR equipment, is suitable when fast results
      of a limited number of samples are requested.

PMID- 22871428
TI  - Akwaton, polyhexamethylene-guanidine hydrochloride-based sporicidal disinfectant:
      a novel tool to fight bacterial spores and nosocomial infections.
AB  - Bacterial spores are of continuing interest to the food and medical industries.
      In efforts to eliminate bacterial spore contamination, a number of sporicidal
      agents have been developed. Most of these compounds must be used carefully in
      very specific circumstances as they are toxic to humans. The sporicidal activity
      of Akwaton, a polyhexamethylene-guanidine hydrochloride (PHMGH)-based
      disinfectant, was tested against Bacillus subtilis spores. PHMGH is a colourless,
      odourless, non-corrosive and non-irritating antimicrobial biocide of the
      guanidine family. Spores suspended in distilled water and spores placed on solid
      surfaces (stainless steel and glass) were used to determine the log(10) reduction
      after exposure to varying concentrations of Akwaton. The minimum sporostatic
      concentration, the minimum sporicidal concentration and the time required for
      sporicidal activity corresponded to 0.06% (w/v), 0.08 % (w/v) and 8.5 min,
      respectively. Disinfectant concentrations of 0.24 % (w/v) and 0.44 % (w/v) killed
      all spores suspended in distilled water within 3 min and 90 s, respectively. The
      sporicidal activity against suspended spores was linearly dependent with respect
      to the concentration of PHMGH and contact time (y(3 min) = 40x-1.6 and y(90 s) =
      20x-0.8 thus y(3 min) = 2y(90 s)). Spores placed on surfaces were more resistant
      to the effect of the disinfectant and the positive linear correlation between the
      sporicidal activity and concentration was not observed. The concentration
      required to kill all spores placed on a surface (stainless steel or glass)
      corresponded to 0.52 % (w/v) for 90 s of contact and 0.36 % (w/v) for 3 min. This
      study demonstrated that PHMGH is an effective sporicidal disinfectant with great
      potential for use in hospitals, laboratories, food industries and households.

PMID- 22871429
TI  - A difficult case: omental transposition flap reconstruction of a large
      radionecrotic axillary ulcer in a patient with extensive previous abdominal
      surgery.
AB  - Radionecrotic ulcers due to breast cancer treatment is a highly morbid and
      disabling condition, causing pain, malodour, need for frequent dressings, reduced
      range of shoulder movements and an unacceptable cosmetic appearance. In patients
      with radiotherapy to the chest and/or axilla and general poor health the usual
      reconstructive options may not be suitable due to regional tissue damage and
      inappropriate long anaesthetic time, respectively. Described procedures include
      the pedicled latisimus dorsi flap, transverse rectus abdominal flap (TRAM) and
      omental transposition flap, as well as free tissue transfer (e.g. free TRAM,
      DIEP). We report a case of a morbidly obese female patient presenting with a
      large radionecrotic ulcer in her left axilla, following mastectomy, axillary
      clearance and local radiotherapy to left chest and axilla for breast cancer. She
      underwent reconstruction using an omental transposition flap, despite previous
      abdominal surgery.

PMID- 22871430
TI  - Hand coverage using venous island flaps.

PMID- 22871431
TI  - Handheld thermography for flap monitoring.

PMID- 22871432
TI  - Radiometals from liquid targets: 94mTc production using a standard water target
      on a 13 MeV cyclotron.
AB  - Solutions containing a high concentration (0.325-0.995 g/ml) of natural-abundance
      ammonium heptamolybdate tetrahydrate ((NH(4))(6)Mo(7)O(24)).4H(2)O were
      irradiated at 13 MeV on a proton-beam cyclotron using a standard liquid target.
      (94m)Tc was produced via the (94)Mo(p,n)(94m)Tc reaction with measured yields of
      110+/-20 MBq for the highest concentrated solution using 5 MUA proton beams for
      60 min. Saturation yields of up to 40+/-6 MBq/MUA were achieved. Pertechnetate
      was isolated from the target mixture with 70.9+/-0.7% efficiency using a solid
      phase extraction resin.

PMID- 22871433
TI  - Microfluidic single vessel production of hypoxia tracer 1H-1-(3-[18F]-fluoro-2
      hydroxy-propyl)-2-nitro-imidazole ([18F]-FMISO).
AB  - We report an automated synthesis of [(18)F]-FMISO utilizing a prototype
      microfluidic radiochemistry module. The instrument allows for production of the
      tracer with 58%+/-2% (11 runs) decay corrected yield. Total time of production,
      including synthesis and purification averages 60 min. Use of the microfluidic
      platform results in a specific activity of 138.6 GBq/MU mol, which is higher than
      previously reported for conventional reactors.

PMID- 22871434
TI  - Half life of 175Hf.
AB  - This work measured the half life of radioisotope (175)Hf, which was produced by
      neutron activation method at the ZF-300-II Intense Neutron Generator in Lanzhou
      University. The half life of (175)Hf, measured by gamma-ray spectrometry using a
      well calibrated GEM-60P coaxial High Purity Germanium (HPGe) detector, has been
      found to be 70.65+/-0.19 days. The present result agrees with the literature data
      well, while the accuracy was improved.

PMID- 22871435
TI  - Nuclear reactions in linear medical accelerators and their exposure consequences.
AB  - Qualitative and quantitative analysis of radionuclides originating inside a
      medical linear accelerator during emission of high-energy therapeutic photon
      beams (15, 18, and 20 MV) is presented. The semiconductor spectrometry method
      allowed to obtain the fluence rate of photons with defined energy and hence, to
      quantify the dose at the chosen points in the vicinity of linac, contribution of
      particular radionuclides and its evolution in time. Typically used materials:
      copper, tungsten, lead, tantalum and their admixtures: antimony, manganese or
      bromine, are activated the most.

PMID- 22871436
TI  - Synthesis of molybdenum nanoparticle by in situ gamma-radiation.
AB  - This paper reports the synthesis of various types of molybdenum nanoparticles
      using in-situ minuscule amount of radioactivity. The radioisotope (99)Mo was
      introduced into the solution of (i) 10(-5)M ammonium molybdate and (ii) mixture
      of 10(-5)M ammonium molybdate and anionic surfactant sodiumdodecyl sulphate
      (SDS). The molybdate ions were changed to nanoparticles due to radiolysis
      initiated by gamma-irradiation in both the cases. The transmission electron
      microscopic images showed 4-15 nm size nanoparticles with spherical shape in
      ammonium molybdate solution. However, the aggregation of nanoparticles could not
      be avoided in this case. The addition of SDS to the solution helped to obtain 10
      60 nm size of spherical molybdenum nanoparticle and 2-10nm wire like molybdenum
      nanoparticle. Interpretation of spectral data advocates that the molybdenum
      nanoparticles might be in MoO(3) form.

PMID- 22871437
TI  - Excitation functions of deuteron induced reactions on natXe: new data up to 20
      MeV.
AB  - In the frame of a systematic study on the activation cross-section of deuteron
      induced reactions on different elements, excitation functions on (nat)Xe were
      investigated up to 20 MeV. The excitation functions for production of the
      radionuclides (127,129,132,134m,135m,136)Cs, (133m,133g,135)Xe, (126,130g)I were
      measured for the first time in the investigated energy range. Stacked gas cell
      irradiation technique and gamma-ray spectrometry were used. The measured data,
      completed with the high energy literature experimental data on (123)Xe,
      (133,131,124,123)I, were compared with the results of the theoretical model
      codes.

PMID- 22871438
TI  - Characterization and MCNP simulation of neutron energy spectrum shift after
      transmission through strong absorbing materials and its impact on tomography
      reconstructed image.
AB  - An ideal neutron radiograph, for quantification and 3D tomographic image
      reconstruction, should be a transmission image which exactly obeys to the
      exponential attenuation law of a monochromatic neutron beam. There are many
      reasons for which this assumption does not hold for high neutron absorbing
      materials. The main deviations from the ideal are due essentially to neutron beam
      hardening effect. The main challenges of this work are the characterization of
      neutron transmission through boron enriched steel materials and the observation
      of beam hardening. Then, in our work, the influence of beam hardening effect on
      neutron tomographic image, for samples based on these materials, is studied. MCNP
      and FBP simulation are performed to adjust linear attenuation coefficients data
      and to perform 2D tomographic image reconstruction with and without beam
      hardening corrections. A beam hardening correction procedure is developed and
      applied based on qualitative and quantitative analyses of the projections data.
      Results from original and corrected 2D reconstructed images obtained shows the
      efficiency of the proposed correction procedure.

PMID- 22871439
TI  - Neutron activation analysis of essential elements in Multani mitti clay using
      miniature neutron source reactor.
AB  - Multani mitti clay was studied for 19 essential and other elements. Four
      different radio-assay schemes were adopted for instrumental neutron activation
      analysis (INAA) using miniature neutron source reactor. The estimated weekly
      intakes of Cr and Fe are high for men, women, pregnant and lactating women and
      children while intake of Co is higher in adult categories and Mn by pregnant
      women. Comparison of MM clay with other type of clays shows that it is a good
      source of essential elements.

PMID- 22871440
TI  - Method for determination of uranium isotopes in environmental samples by liquid
      liquid extraction with triisooctylamine/xylene in hydrochloric media and alpha
      spectrometry.
AB  - Alternative method for determination of uranium isotopes in various environmental
      samples is presented. The method is based on total decomposition of the solid
      materials and preconcentration of liquid samples. The separation of uranium from
      interfering radionuclides and stable matrix elements is attained by liquid-liquid
      extraction with triisooctylamine/xylene in hydrochloric media. After the
      additional removal of stable iron by extraction with diisopropyl ether, purified
      uranium is electrodeposited on stainless steel disks and measured by alpha
      spectrometry. The analytical method has been successfully applied to the
      determination of uranium isotopes in water and bottom sediments from the rivers
      Danube, Ogosta and Tzibritza in Northwestern Bulgaria. The analytical quality was
      checked by analyzing reference materials with different matrices.

PMID- 22871441
TI  - The production, separation, and use of 67Cu for radioimmunotherapy: a review.
AB  - A review of the literature pertaining to the production and separation of (67)Cu.
      This isotope is useful from both therapeutic and diagnostic standpoints due to
      its medium energy beta particle, gamma emissions, and 2.6-day half-life. It has
      been produced via proton, neutron, and gamma irradiations on zinc followed by
      solvent extraction, ion exchange, electrodeposition, and/or sublimation.
      Widespread use of this isotope for clinical studies and preliminary treatments
      has been limited by unreliable supplies, cost, and difficulty in obtaining
      therapeutic quantities.

PMID- 22871443
TI  - Design and simulation of betavoltaic battery using large-grain polysilicon.
AB  - In this paper, we present the design and simulation of a p-n junction betavoltaic
      battery based on large-grain polysilicon. By the Monte Carlo simulation, the
      average penetration depth were obtained, according to which the optimal depletion
      region width was designed. The carriers transport model of large-grain
      polysilicon is used to determine the diffusion length of minority carrier. By
      optimizing the doping concentration, the maximum power conversion efficiency can
      be achieved to be 0.90% with a 10 mCi/cm(2) Ni-63 source radiation.

PMID- 22871442
TI  - Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific
      imaging agent: a reliable thin layer chromatographic system to delineate
      impurities from the 99mTc-antibiotic.
AB  - Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic
      and potential bacteria specific infection imaging agent was evaluated. A good
      radiochemical purity (95%) of the labelled product was obtained after filtering
      the reaction mixture through a 0.22 MUm filter. Scintigraphy study of the
      purified product showed uptake in infectious lesions 45 min after injection and
      abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr
      and 3 hr, respectively. A versatile and reliable chromatographic technique to
      assess the radiochemical purity of (99m)Tc-cefuroxime has also been described.

PMID- 22871444
TI  - The ideal neutron energy spectrum of 241AmLi(alpha,n)10B sources.
AB  - The pure and unperturbed (ideal, at birth) spectra of (241)AmLi(alpha,n)(10)B
      sources were determined using Monte Carlo simulations, along with the neutron
      spectrum measured outside a source's encapsulation. Various parameters that
      affect photon and neutron yields and energy distributions were investigated. The
      source's microparticle size was deduced. Subsequently, the calculated theoretical
      neutron energy spectra of the (241)AmLi(alpha,n) reaction were compared to both
      the ideal spectra and the calculation of Geiger and van der Zwan predominantly
      used since early 1970s.

PMID- 22871445
TI  - Verification of 235U enrichment of fresh VVER-440 fuel assemblies.
AB  - Enrichment of uniformly and non-uniformly enriched ("profiled") fuel assemblies
      in a range of 1.6-4.4% was verified by gamma-ray spectrometry at a nuclear power
      plant (NPP). HPGe detectors and a CdZnTe (CZT) detector, the latter fitting into
      the central tube of the assemblies, were used for obtaining information from
      outer and inner fuel rods. A procedure which has minimal impact on the NPP work
      was developed for verifying freshly arrived assemblies under normal operational
      conditions, and is now in routine use.

PMID- 22871446
TI  - Amorphization and disorder of PrFeO3 thin films after heavy ion irradiation.
AB  - We present structural, morphological, optical absorption and Raman study of 200
      MeV Ag(15+) ion irradiated PrFeO(3) thin film of around 200 nm thickness
      deposited on LaAlO(3) [001] substrate by using the pulsed laser deposition
      technique. X-ray diffraction studies shows that it has an orthorhombic structure
      with Pbnm space group and is grown with (001)-orientation. The substrate-induced
      strain is found to be small and is found to increase for ion fluence. UV-visible
      spectra shows enhancement of optical band gap with ion fluence. At room
      temperature Raman spectra, the different Raman modes observed are classified
      according to the orthorhombic structure. All the observed modes show variation in
      Raman shift with rise in ion fluences. The line width and position variations
      with fluence for observed modes are correlated with octahedral distortion of
      FeO(6), Fe-O bond length and as well as O-Fe-O bond angle. Surface morphology and
      grain size also get affected with ion fluences. Many possibilities have been
      explored to explain the observed results.

PMID- 22871447
TI  - Elastic Recoil Detection Analysis of FeN thin films.
AB  - Thin films of transition metal nitrides are interesting materials due to their
      special features such as high hardness and chemical inertness. In our present
      work, we are reporting Elastic Recoil Detection Analysis of FeN/Si system using
      100 MeV Au beam. Recoils ions were detected using DeltaE-E detector telescope.
      Diffraction pattern of pristine FeN thin films indicates amorphous nature of iron
      nitride thin film. MOKE results show irradiation can be used for controlling the
      magnetic properties such as coercivity.

PMID- 22871449
TI  - Statistical methods applied to gamma-ray spectroscopy algorithms in nuclear
      security missions.
AB  - Gamma-ray spectroscopy is a critical research and development priority to a range
      of nuclear security missions, specifically the interdiction of special nuclear
      material involving the detection and identification of gamma-ray sources. We
      categorize existing methods by the statistical methods on which they rely and
      identify methods that have yet to be considered. Current methods estimate the
      effect of counting uncertainty but in many cases do not address larger sources of
      decision uncertainty, which may be significantly more complex. Thus,
      significantly improving algorithm performance may require greater coupling
      between the problem physics that drives data acquisition and statistical methods
      that analyze such data. Untapped statistical methods, such as Bayes Modeling
      Averaging and hierarchical and empirical Bayes methods, could reduce decision
      uncertainty by rigorously and comprehensively incorporating all sources of
      uncertainty. Application of such methods should further meet the needs of nuclear
      security missions by improving upon the existing numerical infrastructure for
      which these analyses have not been conducted.

PMID- 22871448
TI  - An improved Compton scattering method for determination of concentration of
      solutions.
AB  - An improved Compton scattering method for determination of concentration of low-Z
      solutions is presented. The Monte Carlo (MC) numerical simulation of the
      scattering phenomena is done using the MCNP code. A unique non-linear
      extrapolation method is followed in correcting the scattered intensity for self
      absorption and multiple scattering. The density ratios obtained using non linear
      extrapolated scattered intensity values are free from self-absorption and
      multiple scattering and agree well with the standard ones within experimental
      errors. The sensitivity study of transmission and scattering methods for
      determination of concentration of solutions having closer attenuation parameters
      at 661.6 keV is carried out to predict the range of effectiveness and suitability
      of these methods. The slopes (sensitivity/unit concentration) of the curves
      obtained from scattering method are higher by a factor of 1.26 compared to those
      of the transmission method in the measured range of concentrations.

PMID- 22871451
TI  - Improvement in the calibration time of absolute emission rate of radioisotopic
      neutron sources using vanadyl sulfate bath.
AB  - In this study, for calibration of emission rate of radioisotopic neutron sources,
      a suitable vanadium salt was proposed instead manganese sulfate because the
      shorter half-life of (52)V would facilitate faster neutron yield measurements to
      be made with a shorter delay time between subsequent measurements. Using Monte
      Carlo method, different correction factors of manganese and vanadyl sulfate baths
      were calculated and compared with each other. The results showed that for having
      an appropriate efficiency of VBS, high concentrations of solution must be used.

PMID- 22871450
TI  - Kit formulation for 99mTc-labeling of HYNIC-betaAla-Bombesin((7-14)).
AB  - Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing
      peptide receptors. Several forms of cancer, including lung, prostate, breast, and
      colon express receptors for bombesin-like peptides. Radiolabeled BBN analogs with
      a high affinity for these receptors might be used for scintigraphic imaging. Kit
      formulations for labeling these molecules are important for routine preparation.
      A freeze-dried kit for labeling HYNIC-betaAla-Bombesin((7-14)) with technetium
      99m was prepared, and its storage stability was evaluated by in vitro and in vivo
      assays.

PMID- 22871452
TI  - Using plot experiments to test the validity of mass balance models employed to
      estimate soil redistribution rates from 137Cs and 210Pb(ex) measurements.
AB  - Information on rates of soil loss from agricultural land is a key requirement for
      assessing both on-site soil degradation and potential off-site sediment problems.
      Many models and prediction procedures have been developed to estimate rates of
      soil loss and soil redistribution as a function of the local topography,
      hydrometeorology, soil type and land management, but empirical data remain
      essential for validating and calibrating such models and prediction procedures.
      Direct measurements using erosion plots are, however, costly and the results
      obtained relate to a small enclosed area, which may not be representative of the
      wider landscape. In recent years, the use of fallout radionuclides and more
      particularly caesium-137 ((137)Cs) and excess lead-210 ((210)Pb(ex)) has been
      shown to provide a very effective means of documenting rates of soil loss and
      soil and sediment redistribution in the landscape. Several of the assumptions
      associated with the theoretical conversion models used with such measurements
      remain essentially unvalidated. This contribution describes the results of a
      measurement programme involving five experimental plots located in southern
      Italy, aimed at validating several of the basic assumptions commonly associated
      with the use of mass balance models for estimating rates of soil redistribution
      on cultivated land from (137)Cs and (210)Pb(ex) measurements. Overall, the
      results confirm the general validity of these assumptions and the importance of
      taking account of the fate of fresh fallout. However, further work is required to
      validate the conversion models employed in using fallout radionuclide
      measurements to document soil redistribution in the landscape and this could
      usefully direct attention to different environments and to the validation of the
      final estimates of soil redistribution rate as well as the assumptions of the
      models employed.

PMID- 22871453
TI  - Archeometric studies in the Franciscan Convent of "Santo Antonio" (Recife, PE).
AB  - The purpose of this paper is to characterize the tiles placed on the walls of the
      Franciscan convent of "Santo Antonio" (Recife-PE) and to obtain information about
      the several expansions and structural reforms performed on the convent by dating
      the bricks. For this purpose, a portable energy dispersive x-ray fluorescence
      (EDXRF) was used to characterize the tiles. The dating of the bricks was
      performed using the Thermoluminescence (TL) technique. The results of the EDXRF
      analysis show that the dominant component of the white pigment is lead
      [2PbCO(3).Pb(OH)(2)], used since the ancient times until the 20th century, while
      the dominant element of the blue pigment is cobalt (CoO.Al(2)O(3)), that has been
      used from 1807 until nowadays. The TL dating of bricks indicate that there were
      walls with different periods of construction, being one built around 1765, with a
      deviation of 28 years, whereas other was built later, around 1874, with a
      deviation of 15 years. These results provide new data towards understanding how
      and when the Recife Franciscan convent of "Santo Antonio" was designed and built,
      contributing to other research works presently underway on site.

PMID- 22871454
TI  - Calculation of the solid angle subtended by a cylinder at a point.
AB  - An analytical formula for calculating the solid angle subtended by a cylinder at
      a point has been derived from the general solid angle equation. The formula is
      expressed by double line integrals and by single integrals of simple elementary
      functions. These functions were then integrated and the formula was represented
      by products of some elementary functions and the incomplete Lagrange-Jacobi
      elliptic integrals of the third kind. The final formula was used to calculate
      representative values of solid angles and compare them with literature data.

PMID- 22871455
TI  - Study on the validation of the computer fluid dynamics modeling for a
      continuously flowing water vessel with the industrial SPECT using a radiotracer.
AB  - The industrial Single Photon Emission Computerized Tomography (SPECT) system
      comprised of 30 sets of lead collimated 2 in. NaI(Tl) detectors was built and
      utilized for measuring the spatial distribution of radiotracers as a function of
      time at a predefined cross-sectional level of a tank with a diameter of 300 mm
      and a height of 780 mm. In a stable flow condition, a radiotracer was injected
      into the upstream of a tank and then the measurement data were processed for the
      two dimensional concentration mapping of the radiotracers with a time step of 1s.
      The images were compared with numerical simulation results obtained from the
      Computational Fluid Dynamics modeling that has been incorporated with several
      different kinds of turbulence models. The comparison shows one model gives a
      better result than any others in terms of the similarity of the radiotracer
      distribution pattern. This study demonstrates the significant possibility of
      industrial SPECT technology for visualizing flow characteristics in a multi
      dimensional way and for validating the CFD modeling.

PMID- 22871456
TI  - Thermally assisted photo transfer OSL from deep traps in Al2O3:C grains
      exhibiting different TL peak shapes.
AB  - The present work studies the thermally assisted photo transfer OSL (TAPT OSL)
      signal in the case of Al(2)O(3):C samples showing double-structured main
      dosimetric TL peaks. The measurement signal provides indirect experimental
      evidence regarding the presence of deep traps along with one transfer mechanism
      extremely powerful and efficient. The experimental features of this signal are
      presented along with those yielded for samples with narrow TL peaks for the sake
      of comparison. In the framework of a dosimetric characterization, the
      straightforward relation observed between the TAPT OSL integrated intensity and
      the dose, even if non-linear, implies that this signal could be effectively used
      towards dosimetry purposes in the high dose region up to 250 Gy. Furthermore, the
      study on the influence of the annealing temperature on the TL glow curve shape on
      Al(2)O(3):C grains is attempted. The variety of glow curve shapes reported
      especially in the case of single grains is not affected by high temperature
      annealing, since its effect is dominant even after heating at 1085 degrees C.
      Thus, this variety should not be correlated to the different deep trap
      occupancies, but rather be attributed to a possible structural defect. The main
      dosimetric TL peak af all grains is considered to be a composite of two
      unambiguously different traps of non-first-order kinetics. The low temperature
      part of these traps, reaching a maximum at ~190 degrees C is an electron trap and
      the high temperature part with maximum at ~250 degrees C is a hole trap. TL dose
      response of Al(2)O(3):C grains presenting double peak structures is presented for
      the first time in literature, suggesting the usefulness on the applicability of
      Al(2)O(3):C in the dose regime up to 100 Gy.

PMID- 22871457
TI  - A case report of placental mesenchymal dysplasia with an increased VEGF-D
      expression.
AB  - The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This
      report presents a case of PMD with a female fetus complicated with intrauterine
      growth restriction (IUGR). The ultrasound findings were similar to molar
      pregnancies, but PMD was suspected based on the presence of low beta-hCG levels
      and a normal karyotype. After delivery, pathological examination of the placenta
      showed dilated villi and thick-walled vessels lacking trophoblast proliferation,
      which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was
      found to have increased in the abnormal villi. Whether this is an incidental or X
      linked gene specific event in, IUGR complicated, PMD pathogenesis warrants
      further investigation of VEGF-D expression in PMD.

PMID- 22871459
TI  - Application of a novel multiplex polymerase chain reaction system for 12 X
      chromosomal short tandem repeats to a Japanese population study.
AB  - The analysis of X-chromosomal short tandem repeat (X-STR) polymorphisms has been
      the focus of attention in several researches, mainly due to its applicability in
      the investigation of complex kinship cases. A new 12 X-STR multiplex system
      (GATA172D05, DXS7423, DSX6809, DXS10134, DXS7132, DXS9902, DXS6789, DXS10074,
      DXS8378, DXS9898, DXS10147, and GATA31E08) was developed and applied to a
      Japanese population study. DNA samples from 290 males and 160 females were
      successfully analyzed using the 12 X-STR multiplex system. No mutation was
      detected in the kinship cases involving 34 family trios. The combined powers of
      discrimination of the 12 X-STR loci in males and females were 0.999997 and
      0.9999999996, respectively. We conclude that the combined analysis of 12 X-STR
      loci using this single multiplex polymerase chain reaction system is a powerful
      tool in forensic DNA testing.

PMID- 22871458
TI  - Genotype*age interaction in human transcriptional ageing.
AB  - Individual differences in biological ageing (i.e., the rate of physiological
      response to the passage of time) may be due in part to genotype-specific
      variation in gene action. However, the sources of heritable variation in human
      age-related gene expression profiles are largely unknown. We have profiled genome
      wide expression in peripheral blood mononuclear cells from 1240 individuals in
      large families and found 4472 human autosomal transcripts, representing ~4349
      genes, significantly correlated with age. We identified 623 transcripts that show
      genotype by age interaction in addition to a main effect of age, defining a large
      set of novel candidates for characterization of the mechanisms of differential
      biological ageing. We applied a novel SNP genotype * age interaction test to one
      of these candidates, the ubiquilin-like gene UBQLNL, and found evidence of joint
      cis-association and genotype by age interaction as well as trans-genotype by age
      interaction for UBQLNL expression. Both UBQLNL expression levels at recruitment
      and cis genotype are associated with longitudinal cancer risk in our study
      cohort.

PMID- 22871460
TI  - Implicit learning of conjunctive rule sets: an alternative to artificial
      grammars.
AB  - A single experiment is reported that investigated implicit learning using a
      conjunctive rule set applied to natural words. Participants memorized a training
      list consisting of words that were either rare-concrete and common-abstract or
      common-concrete and rare-abstract. At test, they were told of the rule set, but
      not told what it was. Instead, they were shown all four word types and asked to
      classify words as rule-consistent words or not. Participants classified the items
      above chance, but were unable to verbalize the rules, even when shown a list that
      included the categories that made up the conjunctive rule and asked to select
      them. Most participants identified familiarity as the reason for classifying the
      items as they did. An analysis of the materials demonstrated that conscious micro
      rules (i.e., chunk knowledge) could not have driven performance. We propose that
      such materials offer an alternative to artificial grammar for studies of implicit
      learning.

PMID- 22871461
TI  - Comparison of three groups of patients with usual interstitial pneumonia.
AB  - OBJECTIVE: To determine the clinical characteristics and outcomes of patients
      with lungdominant connective tissue disease (LD-CTD) with a usual interstitial
      pneumonia (UIP) who do not meet the criteria for any form of CTD, and to compare
      these parameters with those of patients with idiopathic pulmonary fibrosis
      (IPF/UIP) and CTD-associated-UIP. METHODS: We conducted a prospective study on
      118 patients diagnosed with UIP [LD-CTD, n = 28; CTDUIP, n = 29; and IPF/UIP, n =
      61]. We compared the clinical characteristics, physiological findings, serum
      albumin concentrations, high-resolution computed tomography (HRCT) imaging data,
      and outcomes among the three groups and used Cox's proportional hazards
      regression analysis to identify variables associated with an increased risk of
      death. RESULTS: The LD-CTD and CTD-UIP patients were younger, more often female,
      and predominantly nonsmokers, compared with the IPF/UIP group. A significant
      difference in survival was evident between patients in the CTD-UIP and IPF/UIP
      groups (p = 0.028), but not between LD-CTD and IPF/UIP (p = 0.164) or between LD
      CTD and CTD-UIP (p = 0.254). The variables associated with poorer survival in all
      UIP patients were (reduced) initial SpO2 level (hazard ratio [HR], 2.89; 95%
      confidence interval [CI] 2.1-3.7; p = 0.009) and lower serum albumin
      concentration (HR 2.16; 95% CI 1.6-2.7; p = 0.008). CONCLUSIONS: LD-CTD has
      distinct clinical characteristics that suggest an autoimmune background
      resembling that of CTD-UIP but differing from that of IPF/UIP. However, LD-CTD
      with a UIP pattern was not associated with improved survival. The resting oxygen
      saturation level and serum albumin concentration were independent predictors of
      mortality in all of the studied UIP patients, regardless of UIP type.

PMID- 22871462
TI  - Cystic lung disease is not uncommon in men with tuberous sclerosis complex.
AB  - OBJECTIVE: To assess the frequency of cystic lung disease suggestive of pulmonary
      lymphangiomyomatosis in men with tuberous sclerosis complex. PATIENTS AND
      METHODS: Retrospective review of CT scans of the chest and abdomen on 29 men with
      tuberous sclerosis complex encountered during a 13-year period, 1998 to 2010.
      RESULTS: Cystic lung disease (defined as >=4 cysts) was seen in 11 of 29 men
      (38%) with tuberous sclerosis complex. The mean age of those with cystic lung
      disease was 46.3 +/- 19.1 years. None of the patients had experienced
      pneumothorax or chylothorax and none had undergone a lung biopsy for evaluation
      of cystic lung disease. Lymphangiomyomatosis had been diagnosed in two of 11
      patients with cystic lung disease. Renal angiomyolipomas were demonstrated in 14
      of 25 patients (56%) with renal imaging available; all 14 had multiple bilateral
      renal involvement. In this limited cohort of patients, the presence of cystic
      lung disease did not correlate with age, smoking exposure or the presence of
      renal AMLs. CONCLUSION: We conclude that tuberous sclerosis complex -related
      lymphangiomyomatosis may not be rare in men but is milder in severity.

PMID- 22871463
TI  - Synthesis and conformational analysis of bicyclic mimics of alpha- and beta-D
      glucopyranosides adopting the biologically relevant 2,5B conformation.
AB  - The synthesis of three conformationally locked d-glucopyranoside analogs
      displaying the hydroxyl pattern of the parent sugar is described. A two carbon
      bridge connecting the C-2 and C-5 atoms of the pyranose ring allows a torsion of
      the sugar ring toward a (2,5)B conformation as confirmed by conformational
      analysis. This conformation is strongly believed to be adopted by the
      oxacarbenium ion-like transition state of several inverting glucosidases.

PMID- 22871465
TI  - Modeling the effects of conservation practices on stream health.
AB  - Anthropogenic activities such as agricultural practices can have large effects on
      the ecological components and overall health of stream ecosystems. Therefore,
      having a better understanding of those effects and relationships allows for
      better design of mitigating strategies. The objectives of this study were to
      identify influential stream variables that correlate with macroinvertebrate
      indices using biophysical and statistical models. The models developed were later
      used to evaluate the impact of three agricultural management practices on stream
      integrity. Our study began with the development of a high-resolution watershed
      model for the Saginaw River watershed in Michigan for generating in-stream water
      quality and quantity data at stream reaches with biological sampling data. These
      in-stream data were then used to explain macroinvertebrate measures of stream
      health including family index of biological integrity (FamilyIBI), Hilsenhoff
      biotic index (HBI), and the number of Ephemeroptera, Plecoptera , and Trichoptera
      taxa (EPTtaxa). Two methods (stepwise linear regression and adaptive neuro-fuzzy
      inference systems (ANFIS)) were evaluated for developing predictive models for
      macroinvertebrate measures. The ANFIS method performed the best on average and
      the final models displayed the highest R(2) and lowest mean squared error (MSE)
      for FamilyIBI (R(2)=0.50, MSE=29.80), HBI (R(2)=0.57, MSE=0.20), and EPTtaxa
      (R(2)=0.54, MSE=6.60). Results suggest that nutrient concentrations have the
      strongest influence on all three macroinvertebrate measures. Consistently,
      average annual organic nitrogen showed the most significant association with
      EPTtaxa and HBI. Meanwhile, the best model for FamilyIBI included average annual
      ammonium and average seasonal organic phosphorus. The ANFIS models were then used
      in conjunction with the Soil and Water Assessment Tool to forecast and assess the
      potential effects of different best management practices (no-till, residual
      management, and native grass) on stream integrity. Based on the model
      predictions, native grass resulted in the largest improvement for all
      macroinvertebrate measures.

PMID- 22871464
TI  - The reproductive potential of the spiders Agelena labyrinthica and Xerolycosa
      nemoralis from areas contaminated with metals.
AB  - Spiders successfully colonize industrially contaminated environments and maintain
      relatively stable populations. The aim of this study was to explain the
      reproductive strategies of two spider species, Xerolycosa nemoralis (an actively
      hunting, sit-and-pursue predator) and Agelena labyrinthica (a web-building, sit
      and-wait predator), between contaminated and uncontaminated sites. Spiders were
      collected from a reference site (Pilica) and two contaminated sites (Olkusz and
      Welnowiec). The amount of energy allocated to the eggs and the number of eggs and
      hatchlings as well as the hatching success were compared. Wolf spiders from the
      contaminated sites produced fewer but relatively energy-rich eggs, whereas web
      building spiders invested their energy in the production of a higher number of
      less energy-rich eggs. The comparisons of the hatching percentages suggested that
      in the contaminated habitats, X. nemoralis achieve a hatching success similar to
      or higher than that of the reference population at Pilica. A. labyrinthica in the
      contaminated sites invested a larger amount of energy in eggs than at the
      reference site, but the hatching success found for this species in the
      contaminated areas was lower than that found at the reference site.

PMID- 22871466
TI  - Source apportionment of organic compounds in Berlin using positive matrix
      factorization - assessing the impact of biogenic aerosol and biomass burning on
      urban particulate matter.
AB  - Source apportionment of 13 organic compounds, elemental carbon and organic carbon
      of ambient PM(10) and PM(1) was performed with positive matrix factorization
      (PMF). Samples were collected at three sites characterized by different
      vegetation influences in Berlin, Germany in 2010. The aim was to determine
      organic, mainly biogenic sources and their impact on urban aerosol collected in a
      densely populated region. A 6-factor solution provided the best data fit for both
      PM-fractions, allowing the sources isoprene- and alpha-pinene-derived secondary
      organic aerosol (SOA), bio primary, primarily attributable to fungal spores,
      bio/urban primary including plant fragments in PM(10) and cooking and traffic
      emissions in PM(1), biomass burning and combustion fossil to be identified. With
      mean concentrations up to 2.6 MUg Cm(-3), biomass burning dominated the organic
      fraction in cooler months. Concentrations for alpha-pinene-derived SOA exceeded
      isoprene-derived concentrations. Estimated secondary organic carbon contributions
      to total organic carbon (OC) were between 7% and 42% in PM(10) and between 11%
      and 60% in PM(1), which is slightly lower than observed for US- or Asian cities.
      Primary biogenic emissions reached up to 33% of OC in the PM(10)-fraction in the
      late summer and autumn months. Temperature-dependence was found for both SOA
      factors, correlations with ozone and mix depth only for the alpha-pinene-derived
      SOA-factor. Latter indicated input of alpha-pinene from the borders, highlighting
      differences in the origin of the precursors of both factors. Most factors were
      regionally distributed. High regional distribution was found to be associated
      with stronger influence of ambient parameters and higher concentrations at the
      background station. A significant contribution of biogenic emissions and biomass
      burning to urban organic aerosol could be stated. This indicates a considerable
      impact on PM concentrations also in cities in a densely populated area, and
      should draw the attention concerning health aspects not only to cardio-vascular
      diseases but also to allergy issues.

PMID- 22871467
TI  - A prospective study of the feasibility and acceptability of a Web-based,
      electronic patient-reported outcome system in assessing patient recovery after
      major gynecologic cancer surgery.
AB  - PURPOSE: The purposes of this study are to evaluate the feasibility of capturing
      patient-reported outcomes (PROs) electronically and to identify the most common
      distressing symptoms in women recovering from major gynecologic cancer surgery.
      METHODS: This was a prospective, single-arm pilot study. Eligible participants
      included those scheduled for a laparotomy for presumed or known gynecologic
      malignancy. Patients completed a Web-based "STAR" (Symptom Tracking and Reporting
      for Patients) questionnaire once preoperatively and weekly during the 6-week
      postoperative period. The questionnaire consisted of the patient adaptation of
      the NCI CTCAE 3.0 and EORTC QLQ-C30 3.0. When a patient submitted a response that
      was concerning, an automated email alert was sent to the clinician. The patient's
      assessment of STAR's usefulness was measured via an exit survey. RESULTS: Forty
      nine patients completed the study. The procedures included the following:
      hysterectomy+/-staging (67%), resection of tumor (22%), salpingo-oophorectomy
      (6%), and other (4%). Most patients (82%) completed at least 4 sessions in STAR.
      The CTC generated 43 alerts. These alerts resulted in 25 telephone contacts with
      patients, 2 ER referrals, one new appointment, and one pharmaceutical
      prescription. The 3 most common patient-reported symptoms generating an alert
      were as follows: poor performance status (19%), nausea (18%), and fatigue (17%).
      Most patients found STAR useful (80%) and would recommend it to others (85%).
      CONCLUSION: Application of a Web-based, electronic STAR system is feasible in the
      postoperative period, highly accepted by patients, and warrants further study.
      Poor performance status, nausea, and fatigue were the most common distressing
      patient-reported symptoms.

PMID- 22871468
TI  - Robotic single port total laparoscopic hysterectomy for endometrial cancer
      patients.

PMID- 22871469
TI  - Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase
      (FAK) in high grade endometrial carcinoma.
AB  - OBJECTIVE: The deregulation of E-cadherin is associated with Src/FAK signaling
      axis and histone deacetylase (HDAC)/EZH2 activity. However, the association
      between EZH2 and FAK and its clinical significance in endometrial carcinoma has
      not been reported. METHODS: 202 archived cases of endometrial carcinoma (1996
      2000) were reviewed and divided into two subtypes. TMAs were developed as per
      established procedures. EZH2, FAK, and pFAK immunohistochemical stains were
      performed and the expression was scored as negative (0), low (1) and high (2).
      Proper statistical analysis was used to assess the correlation between the
      expression profiles and the clinicopathological parameters and clinical outcome.
      RESULTS: A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were
      identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63%
      of type-2 tumors (p<0.001). FAK and pFAK overexpression was only seen in 24.8%
      and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors,
      respectively (p<0.001). A positive correlation between the expression of EZH2,
      FAK, pFAK and PTEN (p<0.0001) was found. The overexpression of EZH2, FAK, and
      pFAK were significantly associated with high histologic grade, angiolymphatic
      invasion, lymph node metastasis, myometrial invasion and cervical involvement
      (p<0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2
      (p=0.0024), FAK and pFAK (p=0.0001) was significantly associated with decreased
      overall survival. CONCLUSION: The overexpression of EZH2, FAK and pFAK correlates
      with well established pathologic risk factors and may predict a more aggressive
      biologic behavior in endometrial carcinoma, transforming these proteins into
      potential therapeutic targets for treatment of endometrial cancer.

PMID- 22871470
TI  - A role for NT-3 in the hyperinnervation of neonatally wounded skin.
AB  - Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates
      sensory neuronal survival and growth. Here we report that NT-3 plays a critical
      permissive role in cutaneous sensory nerve sprouting that contributes to pain and
      sensitivity following skin wounding in young animals. Sensory terminal sprouting
      in neonatally wounded dermis and epidermis is accompanied by increased NT-3
      transcription, NT-3 protein levels, and NT-3 protein release 3-7 days post skin
      injury in newborn rats and mice. Functional blockade of NT-3 activity with
      specific antibodies greatly reduces sensory neurite outgrowth induced by wounded
      skin, but not by naive skin, in dorsal root ganglion/skin co-cultures. The
      requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the
      absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT
      3(+/-)lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is
      a critical factor mediating the sensory nerve sprouting that underlies
      hypersensitivity and pain following skin injury.

PMID- 22871472
TI  - 'Pseudo-neglect' in CRPS is closer to 'anti-neglect' than to classical hemi
      neglect?

PMID- 22871471
TI  - Placebo-induced analgesia in an operant pain model in rats.
AB  - Analgesia is particularly susceptible to placebo responses. Recent studies in
      humans have provided important insights into the neurobiology underlying placebo
      induced analgesia. However, human studies provide incomplete mechanistic
      explanations of placebo analgesia because of limited capacity to use cellular,
      molecular, and genetic manipulations. To address this shortcoming, this article
      describes the development of a rat model of conditioned analgesia in an operant
      pain assay. Specifically, rats were conditioned to associate a placebo
      manipulation with the analgesic effect of 1mg/kg morphine (subcutaneously) on
      facial thermal pain. We found that conditioned (placebo) responding bore 3 of the
      hallmarks of placebo-induced analgesia: (1) strong interanimal variability in the
      response, (2) suppression by the opiate antagonist naloxone (5mg/kg
      subcutaneously), and (3) a positive predictive relationship between the
      unconditioned analgesic effect and the conditioned (placebo) effect. Because of
      the operant nature of the assay and the use of only a mild noxious thermal
      stimulus, we suggest that these results provide evidence of placebo-induced
      analgesia in a preclinical model that utilizes an affective behavioral end point.
      This finding may provide opportunities for invasive preclinical studies allowing
      greater understanding of placebo-induced analgesia, thus paving the way for
      avenues to harness its benefits.

PMID- 22871473
TI  - PICALM-MLLT10 acute myeloid leukemia: a French cohort of 18 patients.
AB  - The PICALM-MLLT10 fusion gene, generated by the t(10;11)(p12-13;q14-21)
      translocation, is a rare but recurrent event in acute leukemias. In this study,
      we assessed the characteristics and outcome of 18 PICALM-MLLT10 AML patients. As
      compared with non PICALM-MLLT10 patients (n=72), PICALM-MLLT10 AML were
      characterized by more frequent extramedullary diseases, CD7 expression and higher
      platelet counts. Three out of four therapy-related PICALM-MLLT10 AMLs had been
      previously treated for diffuse large B-cell lymphoma. The complete response rate
      was 71% after intensive chemotherapy. PICALM-MLLT10 patients had a shorter median
      overall survival than patients with favorable cytogenetics (12 months vs. not
      reached, p=0.07) but not significantly different from those of intermediate (26
      months, p=0.32) or unfavorable cytogenetic groups (8 months, p=0.13). Long term
      responses were achieved in a subset of patients after allogeneic stem-cell
      transplantation but also after high-dose cytarabine.

PMID- 22871474
TI  - Involvement of a common progenitor cell in core binding factor acute myeloid
      leukaemia associated with mastocytosis.
AB  - In core binding factor (CBF) acute myeloid leukaemia (AML), realtime quantitative
      PCR is useful to quantify the fusion transcript ratio (CBFbeta-MYH11 and AML1
      ETO, in case of inv(16) and t(8;21) respectively) in peripheral blood and bone
      marrow during the courses of chemotherapy, in order to monitor minimal residual
      disease (MRD). In two cases of CBF AML associated with systemic mastocytosis
      (SM), the persistence of mast cells and the detection of a high ratio of fusion
      transcript, in bone marrow, during the courses of chemotherapy, led us to
      determine whether the mast cell component of the disease carried the same
      molecular alterations as leukaemic blasts. We demonstrate that sorted mast cells
      carried CBF abnormality. These observations point out the lack of specificity of
      MRD monitoring by RQ-PCR in these exceptional AML cases with SM. Moreover, this
      suggests that leukaemic blasts and mast cells derive from a common malignant
      progenitor.

PMID- 22871475
TI  - Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug
      monitoring performance.
AB  - BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires
      good practice in dose selection and monitoring of serum levels. Suboptimal
      therapy occurs with breakdown in the process of drug dosing, serum blood
      sampling, laboratory processing and level interpretation. Unintentional
      underdosing may result. This improvement effort aimed to optimise this process in
      an academic teaching hospital using Six Sigma process improvement methodology.
      METHODS: A multidisciplinary project team was formed. Process measures considered
      critical to quality were defined, and baseline practice was examined through
      process mapping and audit. Root cause analysis informed improvement measures.
      These included a new dosing and monitoring schedule, and standardised assay
      sampling and drug administration timing which maximised local capabilities. Three
      iterations of the improvement cycle were conducted over a 24-month period.
      RESULTS: The attainment of serum level sampling in the required time window
      improved by 85% (p<=0.0001). A 66% improvement in accuracy of dosing was observed
      (p<=0.0001). Unnecessary dose omission while awaiting level results and
      inadvertent disruption to therapy due to dosing and monitoring process breakdown
      were eliminated. Average daily dose administered increased from 3.39 mg/kg to
      4.78 mg/kg/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin
      usage process performance. Local process related factors may adversely affect
      adherence to practice guidelines for gentamicin, a drug which is complex to use.
      It is vital to adapt dosing guidance and monitoring requirements so that they are
      capable of being implemented in the clinical environment as a matter of routine.
      Improvement may be achieved through a structured localised approach with
      multidisciplinary stakeholder involvement.

PMID- 22871476
TI  - Sono-thermal pre-treatment of waste activated sludge before anaerobic digestion.
AB  - Sonication and thermalization can be applied successfully to disrupt the complex
      waste activated sludge (WAS) floc structure and to release extra and intra
      cellular polymeric substances into soluble phase along with solubilization of
      particulate organic matters, before sludge digestion. In this study, sonication
      has been combined with thermalization to improve its disintegration efficiency.
      It was aimed that rise in temperature occurring during the sonication of sludge
      was used to be as an advantage for the following thermalization in the combined
      pre-treatment. Thus, the effects of sonication, thermalization and sono
      thermalization on physical and chemical properties of sludge were investigated
      separately under different pre-treatment conditions. The disintegration
      efficiencies of these methods were in the following descending order: sono
      thermalization > sonication > thermalization. The optimum operating conditions
      for sono-thermalization were determined as the combination of 1-min sonication at
      1.0 W/mL and thermalization at 80  degrees C for 1h. The influences of sludge pre
      treatment on biodegradability of WAS were experienced with biochemical methane
      potential assay in batch anaerobic reactors. Relative to the control reactor,
      total methane production in the sono-thermalized reactor increased by 13.6% and
      it was more than the sum of relative increases achieved in the sonicated and
      thermalized reactors. Besides, the volatile solids and total chemical oxygen
      demand reductions in the sono-thermalized reactor were enhanced as well. However,
      it was determined that sludge pre-treatment techniques applied in this study was
      not feasible due to their high energy requirements.

PMID- 22871477
TI  - A theoretical framework for measuring knowledge in screening decision aid trials.
AB  - OBJECTIVE: To describe a theoretical framework for assessing knowledge about the
      possible outcomes of participating in bowel cancer screening for the faecal
      occult blood test. METHODS: The content of the knowledge measure was based on the
      UK General Medical Council's screening guidelines and a theory-based approach to
      assessing gist knowledge (Fuzzy Trace Theory). It comprised conceptual and
      numeric questions to assess knowledge of the underlying construct (e.g. false
      positive concept) and the approximate numbers affected (e.g. likelihood of a
      false positive). The measure was used in a randomised controlled trial involving
      530 adults with low education, to compare the impact of a bowel screening
      decision aid with a screening information booklet developed for the Australian
      Government National Bowel Cancer Screening Program. RESULTS: The numeric
      knowledge scale was particularly responsive to the effects of the decision aid;
      at follow-up decision aid participants' numeric knowledge was significantly
      greater than the controls (P<0.001). This contrasts with the conceptual knowledge
      scale which improved significantly in both groups from baseline to follow-up
      (P<0.001). CONCLUSION: Our theory-based knowledge measure was responsive to
      change in conceptual knowledge and to the effect on numeric knowledge of a
      decision aid. PRACTICE IMPLICATIONS: This theoretical framework has the potential
      to guide the development of knowledge measures in other screening settings.

PMID- 22871478
TI  - Serum proteomics of methamphetamine addicts and up-regulation of complement
      factor H related to methamphetamine addiction.
AB  - Methamphetamine (METH) is a new type of drug with strong tolerance and addiction.
      However, the molecular mechanisms underlying the processes of METH addiction are
      still not fully understood. To determine possible biomarkers and mechanisms that
      are responsible for METH addiction, a 2-DE based proteomics approach was used to
      evaluate the changes in protein expression of the serum in Chinese patients
      addicted to METH, which to the best of our knowledge is the first study of its
      kind. We identified five proteins that were markedly altered and complement
      factor H (CFH), the most stably up-expressed protein in each 2-DE experiment, was
      further studied using the rat conditioned place preference (CPP) model to detect
      any changes to its expression in the sera and six brain regions of interest. We
      report, for the first time, that CFH was positive related to METH addiction.

PMID- 22871479
TI  - Thermoregulation by an Australian murine rodent, the ash-grey mouse (Pseudomys
      albocinereus).
AB  - We examine here the thermal physiology of the ash-grey mouse, as there is a
      paucity of data to explain how Australian rodents meet thermoregulatory demands.
      Most ash-grey mice remained normothermic over a range of ambient temperatures (10
      degrees C to 30  degrees C), although they became hyperthermic at high ambient
      temperatures. One individual entered torpor at ambient temperatures of 20 
      degrees C and 25  degrees C, with minimal body temperatures of 24.5  degrees C
      and 28.4  degrees C respectively, before spontaneously arousing. This is the
      first evidence of torpor use by an Australian murine rodent. Our data suggest
      that although ash-grey mice have the physiological ability to use torpor, it is
      used rarely, presumably due to other behavioural and physiological adaptations.
      Their higher-than-expected basal metabolic rate (1.56+/-0.25 mL O(2)g(-1) h(-1))
      indicates that ash-grey mice do not have a frugal approach to energy expenditure.
      Other standard physiological variables were typical of a generalised rodent. A
      readily-available omnivorous diet, nocturnal activity, semi-fossorial habit and
      social behaviour presumably allow a high energy lifestyle. A reluctance to use
      torpor, despite an apparent physiological ability to do so, supports the idea
      that the use of torpor reflects a net balance between the costs and benefits of a
      heterothermic thermoregulatory strategy.

PMID- 22871480
TI  - Building, supporting, and sustaining a network for HIV-infected health workers:
      interview with Phyllis Kisabei, CHRN. Interview by Jackline G. Opollo.

PMID- 22871481
TI  - Digital gaming for HIV prevention with young adolescents.
AB  - The search for intervention strategies appropriate for young adolescents has
      recently led to the use of digital games. Digital gaming interventions are
      promising because they may be developmentally appropriate for adolescent
      populations. The gaming approach also capitalizes on an inherent interest to
      adolescents and circumvents traditional barriers to access to prevention
      interventions faced in some geographical areas. Notwithstanding, research on
      gaming in HIV prevention is quite limited. In this review article, we examine the
      need for contextually relevant HIV prevention interventions among young
      adolescents. From this, we provide a theoretical framework for exploring
      contextually relevant HIV risk factors and a foundation for gathering and using
      input from the target population to adapt an existing game or to create a
      developmentally appropriate and contextually relevant HIV prevention game.

PMID- 22871482
TI  - Social support networks and primary care use by HIV-infected drug users.
AB  - HIV-infected current and former drug users utilize primary care and preventive
      health services at suboptimal rates, but little is known about how social support
      networks are associated with health services use. We investigated the
      relationship between social support networks and the use of specific types of
      health services by HIV-infected drug users receiving methadone maintenance. We
      found that persons with greater social support, in particular more social network
      members or more network members aware of their HIV status, were more likely to
      use primary care services. In contrast, social support networks were not related
      to emergency room or inpatient hospital use. Interventions that build social
      support might improve coordinated and continuous health services utilization by
      HIV-infected persons in outpatient drug treatment.

PMID- 22871483
TI  - Model analysing the antioxidant responses of leaves and roots of switchgrass to
      NaCl-salinity stress.
AB  - Salinity is a major environmental stress and a substantial constraint on plant
      production. The objective of this research was to better understand the
      mechanisms of the antioxidant responses of leaves and roots to NaCl-salinity
      stress in switchgrass (Panicum virgatum L.). The effects of NaCl-salinity stress
      (1, 3, 5, 10 and 15gNaCl/kgdrysoil) on lipid peroxidation and antioxidant
      defences in switchgrass leaves and roots were investigated, and a model analysis
      was conducted. The results of the correlation analyses indicated that CAT, POD
      and SOD were more important than APX, GSH and MDA, whereas the model analyses
      suggested that the latter three biochemical indices were more sensitive than the
      former three indices to NaCl-salinity in switchgrass. The connective models of
      APX, GSH, MDA, CAT, SOD and POD between leaves and roots were obtained,
      respectively. The new models can be used to closely predict the biochemical index
      values in switchgrass roots or leaves.

PMID- 22871484
TI  - Extraversion and short-term memory for chromatic stimuli: an event-related
      potential analysis.
AB  - The present study investigated extraversion-related individual differences in
      visual short-term memory (VSTM) functioning. Event related potentials were
      recorded from 50 introverts and 50 extraverts while they performed a VSTM task
      based on a color-change detection paradigm with three different set sizes.
      Although introverts and extraverts showed almost identical hit rates and reaction
      times, introverts displayed larger N1 amplitudes than extraverts independent of
      color change or set size. Extraverts also showed larger P3 amplitudes compared to
      introverts when there was a color change, whereas no extraversion-related
      difference in P3 amplitude was found in the no-change condition. Our findings
      provided the first experimental evidence that introverts' greater reactivity to
      punctuate physical stimulation, as indicated by larger N1 amplitude, also holds
      for complex visual stimulus patterns. Furthermore, P3 amplitude in the change
      condition was larger for extraverts than introverts suggesting higher sensitivity
      to context change. Finally, there were no extraversion-related differences in P3
      amplitude dependent on set size. This latter finding does not support the
      resource allocation explanation as a source of differences between introverts and
      extraverts.

PMID- 22871486
TI  - One pot efficient diversity oriented synthesis of polyfunctional styryl
      thiazolopyrimidines and their bio-evaluation as antimalarial and anti-HIV agents.
AB  - An efficient one pot synthesis of a series of pluripotent (E)-1-(3-methyl-5-aryl
      7-styryl-5H-thiazolo[3,2-a]pyrimidin-6-yl)-3-arylprop-2-en-1-ones is reported. It
      involves reaction of 5-acetyl-6-methyl-4-aryl-dihydropyrimidine-2-thiones,
      propargyl bromide and aromatic aldehydes in presence of ethanolic KOH. The newly
      synthesized compounds were evaluated for antimalarial activity against Plasmodium
      falciparum and as HIV-RT inhibitors. Most of the compound displayed potent
      antimalarial activity with IC(50)<2 MUg/mL. Compounds 6, 11 and 20 showed better
      activity against P. falciparum K1 strains in comparison to standard drug
      chloroquine. Compounds 6, 11, and 16 exhibited 73.44, 66.92, and 70.81% HIV-RT
      inhibition at 100 MUg/mL.

PMID- 22871485
TI  - Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1
      phosphatase activity.
AB  - Previously, we demonstrated that the multiple kinase inhibitor sorafenib mediates
      the repression of phospho-STAT3 in hepatocellular carcinoma cells. In this study,
      we used this kinase-independent mechanism as a molecular basis to use sorafenib
      as scaffold to develop a novel class of SHP-1-activating agents. The proof of
      principle of this premise was provided by SC-1, which on replacement of N
      methylpicolinamide by a phenylcyano group showed abolished kinase activity while
      retaining phospho-STAT3 repressive activity. Structural optimization of SC-1 led
      to compound 6, which repressed phospho-STAT3 through SHP-1 activation and
      inhibited PLC5 cell proliferation at sub-micromolar potency. In light of the
      pivotal role of phospho-STAT3 in promoting tumorigenesis and drug resistance,
      this novel SHP-1-activating agent may have therapeutic relevance in cancer
      therapy.

PMID- 22871487
TI  - Seeing single atoms.
AB  - New discoveries and ideas often occur at the confluence of events and
      technologies that allow them to happen. So it was with the first electron
      microscopic observations of individual atoms at the University of Chicago
      laboratory of Albert Crewe forty years ago. This paper will describe the
      technologies developed then, present some of the historical instrumental details
      and describe the rationale for the designs that came about in that laboratory
      over a period of about a decade.

PMID- 22871488
TI  - Short-term outcomes of newborns with perinatal acidemia who are not eligible for
      systemic hypothermia therapy.
AB  - OBJECTIVE: To determine short-term outcomes of infants who had perinatal acidemia
      and were evaluated for hypothermia therapy but did not qualify based on a
      standardized neurologic examination. STUDY DESIGN: Retrospective, single-site
      cohort study of inborn infants of >= 36 weeks gestation who had perinatal
      acidemia from October 2005-September 2008 and had a standardized neurologic
      examination performed by a certified neonatologist to assess eligibility for
      hypothermia therapy. An abnormal short-term nursery outcome was defined as death,
      seizures, brain magnetic resonance imaging consistent with hypoxic-ischemic
      encephalopathy, abnormal neurologic examination at discharge, gastrostomy tube
      feeding, or inability to nipple all feeds beyond the first week of age. RESULTS:
      One hundred forty-four (0.3%) of 46 887 newborns with perinatal acidemia had a
      neurologic examination performed that was either normal (n = 29) or consistent
      with mild encephalopathy (1 or 2 abnormal categories; n = 60). Of the latter
      infants classified as having mild encephalopathy, 12 (20%) experienced an
      abnormal short-term outcome (feeding difficulties, n = 8; abnormal neurologic
      examination at discharge, n = 7; abnormal brain magnetic resonance imaging, n =
      6; seizures, n = 5; gastrostomy, n = 1; or death, n = 1). CONCLUSIONS: Twenty
      percent of newborns with perinatal acidemia and a neurologic examination that
      revealed only mild encephalopathy had abnormal short-term outcomes that could be
      attributed to the encephalopathy. Adjunctive tools or biomarkers for optimal
      assessment of infants with fetal acidemia for hypothermia therapy are needed.

PMID- 22871489
TI  - Markers of maternal depressive symptoms in an urban pediatric clinic.
AB  - OBJECTIVE: To identify markers of maternal depressive symptoms in medical records
      of children aged 1-6 years. STUDY DESIGN: Using a case-control methodology,
      mothers who were screened for depressive symptoms with the Quick Inventory of
      Depressive Symptomatology Self-Rated Questionnaire (QIDS-SR) at well-child visits
      between June 2006 and June 2008 in an inner-city pediatric clinic were grouped
      into cases with depressive symptoms (QIDS-SR score >= 11) and controls with no
      symptoms (QIDS-SR score <= 5). Potential markers for maternal depressive symptoms
      were collected from the children's medical record and grouped into 3 domains: (1)
      child health and development (eg, maternal concerns/negative attributions
      regarding the child's behavior); (2) child health care utilization (eg, missed
      appointments); and (3) maternal psychosocial factors (eg, single parent). The
      association between maternal depressive symptoms and each factor was determined
      using multiple logistic regression to calculate aORs. RESULTS: Maternal
      depressive symptoms were significantly associated with reports of
      concerns/negative attributions about the child's behavior (aOR, 2.35; P = .01)
      and concerns about speech (aOR, 2.40; P = .04) and sleep (aOR, 7.75; P < .001);
      these were identified at the visit when the depression screening was done. Other
      associations included history of maternal depression (aOR, 4.94; P = .001) and a
      previous social work referral (aOR, 1.98; P = .01). CONCLUSION: Information
      readily available to pediatricians was associated with maternal depressive
      symptoms and can serve as clinical markers to help identify at-risk mothers
      during well-child visits.

PMID- 22871490
TI  - Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt
      phenomenon in 107 referrals.
AB  - OBJECTIVE: To examine the presentation characteristics of patients with
      Kaposiform hemangioendothelioma (KHE) to describe the spectrum of disease and
      risk factors for Kasabach-Merritt phenomenon (KMP). STUDY DESIGN: A retrospective
      review of 163 patients referred to the Vascular Anomalies Center at Children's
      Hospital Boston for KHE between 1991 and 2009 identified 107 patients with
      sufficient data for inclusion. RESULTS: The prevalence of KHE in Massachusetts is
      ~0.91 case per 100000 children. KHE manifested in infancy in 93% of cases, with
      60% as neonates. Common presenting features included enlarging cutaneous lesion
      (75%), thrombocytopenia (56%), and musculoskeletal pain or decreased function
      (23%). Cutaneous KHE favored the extremities, especially overlying joints. In our
      cohort, 71% developed KMP (11% after initial presentation), and 11% of patients
      lacked cutaneous findings. Retroperitoneal and intrathoracic lesions, though less
      common, were complicated by KMP in 85% and 100% of cases, respectively. Compared
      with superficial lesions, KHE infiltrating into muscle or deeper was 6.3-fold
      more likely to manifest KMP and 18-fold higher if retroperitoneal or
      intrathoracic. KHE limited to bone or presenting after infancy did not manifest
      KMP. CONCLUSION: An enlarging cutaneous lesion is the most common presenting
      feature of KHE in infancy. Older patients with KHE or those lacking cutaneous
      manifestations present with musculoskeletal complaints or atypical symptoms. The
      risk of KMP increases dramatically when tumor infiltrates muscle or when KHE
      arises in the retroperitoneum or mediastinum.

PMID- 22871491
TI  - Physical activity assessment in adolescents with limb salvage.
AB  - OBJECTIVES: To evaluate ambulatory activity differences between youth with limb
      salvage procedures and typically developing youth (TDY) and assess differences in
      self-reported activity levels in the 2 groups, to provide a basis for physical
      activity assessment in patients who had undergone limb salvage surgery and
      treatment planning that incorporates regaining normal physical and daily living
      activities. STUDY DESIGN: In this cohort comparison study, we compared ambulatory
      and self-reported activity levels in 20 youth (aged 11.7-20.8 years) who had
      undergone limb salvage surgery and a sex- and age-matched comparison cohort of 20
      TDY. StepWatch activity monitor and Activity Scale for Kids data were used to
      answer these questions. RESULTS: Significant differences were found between the
      youth who had undergone limb salvage surgery and the TDY in total time active
      each day (43% vs 48%; P = .03), median total strides per day (4487 vs 7671; P =
      .001), and amount of time per day at high activity levels (20 minutes vs 47
      minutes; P = .001). Self-reported overall physical activity, locomotion, and
      standing Activity Scale for Kids subscale scores were significantly lower in the
      youth undergoing limb salvage surgery compared with the TDY (summary score, 88.3
      vs 97.7; P = .001). CONCLUSION: Patients undergoing limb salvage surgery exhibit
      reduced physical activity compared with normal age-matched controls.

PMID- 22871492
TI  - Scenario of solid waste reuse in Khulna city of Bangladesh.
AB  - The reuse and recycling of waste materials are now sincerely considered to be an
      integral part of solid waste management in many parts of the world. In this
      context, a vast number of options ranging from small scale decentralized to
      larger scale centralized plants have been adopted. This study aimed at
      investigating the waste reuse schemes in Khulna city located in the southern part
      of Bangladesh and ranked third largest city in the country. The shops for
      reusable material (SRM) were mostly situated around railway, waterway, and truck
      station markets which provided easy transportation to further locations. For the
      reuses of waste materials and products, a chain system was found to collect
      reusable wastes under a total number of 310 identified SRM with 859 persons
      directly or indirectly involved in the scheme. This was a decentralized waste
      management system with self sufficient (autonomous) management. According to mass
      balance, about 38.52 tons d(-1) solid wastes were reused in Khulna city area,
      accounting for 7.65% of the total generated wastes. This study revealed that
      apparently a silent, systematic, smooth, and clean reuse chain has been
      established in Khulna city area under private initiatives, whose sustainability
      was confirmed over the years in the country without any official or formal funds.
      However, proper adjustment between the higher and lower chain in the materials
      flow path, as well as personal hygiene training for the workers, would further
      improve the achievements of the established reuse scheme.

PMID- 22871493
TI  - [A prospective, multicentre study on the activity of general and digestive
      surgery residents based on the use of the computerised logbook].
AB  - INTRODUCTION: There are no quantified data on the real activity carried out by
      residents during the 5 years of training in the specialty of general and
      digestive surgery (GGS) in Spain. There are also limited data on programs in
      other surgical specialities, and in other countries. The aim of the study is to
      estimate the mean overall surgical activity by specific skill areas and by the
      level of complexity of the Spanish program in the specialty of GGS. PATIENTS AND
      METHOD: A prospective, observational, multicentre study was performed on the
      activity of GGS residents in Spain using the Resident Computerised Logbook of the
      Spanish Surgeons Association (LIR-AEC). Each of the residents registered their
      own activity supervised by their tutor. The sample period was 6 months. The
      medians of the annual activity and the period of residency were calculated from
      the results. RESULTS: Surgical activity: during the residency, it was estimated
      that that they attended 1,325 operations, 654 (49%) as lead surgeon. Health care
      activity: the mean number of times on-call was 5.2+/-1.8 per month. Activity in
      outpatient clinics was 548 first visits, and almost double for second visits.
      Scientific activity: the total number of courses and conferences attended was 34.
      The estimated mean number of presentations at conferences was 14, with 3
      publications. CONCLUSIONS: LIR-AEC is a suitable tool to verify activity in the
      Spanish GGS Program. These results may be useful for comparing with training
      programs in other countries and in other surgical specialties.

PMID- 22871494
TI  - Evaluation of Sofia fluorescent immunoassay analyzer for influenza A/B virus.
AB  - BACKGROUND: The influenza virus causes seasonal epidemics which are associated
      with high morbidity and mortality. Rapid diagnostics tests (RDT) are frequently
      used to make a quick influenza diagnosis to confirm the clinical suspicion,
      despite their low sensitivity. OBJECTIVES: Assess the performance of the Sofia
      Influenza A+B Fluorescence Immunoassay (Quidel, San Diego, CA). STUDY DESIGN:
      Nasopharyngeal swabs, taken from 241 patients (influenza A (n=73)/B (n=72),
      negative samples (n=96)) were analyzed using the Sofia Influenza A+B Fluorescence
      Immunoassay, BinaxNOW Influenza A/B antigen kit (Alere Inc., USA), Directigen EZ
      Flu A and B (Becton Dickinson, USA), real-time RT-PCR and an influenza virus
      culture. RESULTS: There was a significant difference between the performance of
      rapid antigen tests and the Sofia FIA, when compared to the RT-PCR, in the
      detection of influenza strain A and B. Indeed, the Sofia FIA displayed
      sensitivities of 82.2% and 77.8% for strains A and B respectively, whereas
      sensitivities of BinaxNOW Influenza A/B antigen kit, and Directigen Flu A and B
      were 54.8%, and 68.5% for influenza A, and 62.5%, and 52.8% for influenza B
      respectively. The average RT-PCR threshold cycle (C(t)) (+/-SD) for the Sofia
      Influenza A+B Fluorescence Immunoassay-positive specimens was higher than those
      of the BinaxNOW Influenza A/B antigen and the Directigen EZ Flu A and B kit
      positive specimens. CONCLUSION: Compared to other RDTs, the Sofia Influenza A+B
      Fluorescence Immunoassay is a sensitive, and rapid method for the detection and
      discrimination between influenza A and B.

PMID- 22871495
TI  - The putative tumor suppressor miR-524-5p directly targets Jagged-1 and Hes-1 in
      glioma.
AB  - Notch pathway plays critical role in stem cell maintenance and angiogenesis, as
      well as cell fate decisions of cancer. However, concrete mechanisms of notch
      pathway regulation in glioma were not well known, especially mediated by
      microRNAs. In this study, we identified a brain-specific miRNA, miR-524-5p, which
      was associated with the pathological grade and overall survival of gliomas.
      Restorated expression of miR-524-5p in glioma suppressed cell proliferation and
      invasion both in vitro and in vivo. Using bioinformatics and biological
      approaches, we found that Jagged-1 and Hes-1, two key components of notch
      pathway, were direct targets of miR-524-5p. Knocking down of Jagged-1 or Hes-1
      partially phenocopied miR-524-5p re-expression, whereas forced expression of
      Jagged-1 or Hes-1 reversed the effects of miR-524-5p on proliferation and
      invasion of glioma. Moreover, miR-524-5p levels in glioma samples were inversely
      correlated with Jagged-1 and Hes-1 and their overexpressions were associated with
      poor survival. Thus, we have identified that miR-524-5p behaves as a tumor
      suppressor by negatively targeting Jagged-1 and Hes-1 and provides an additional
      option to inhibit this oncogene in gliomas.

PMID- 22871496
TI  - Pharmacological targeting of mammalian target of rapamycin inhibits ovarian
      granulosa cell tumor growth.
AB  - Few targeted therapies have been developed for ovarian granulosa cell tumor
      (GCT), even though it represents 5% of all malignant ovarian tumors in women. As
      misregulation of PI3K/AKT signaling has been implicated in GCT development, we
      hypothesized that the AKT signaling effector mammalian target of rapamycin (mTOR)
      may play a role in the pathogenesis of GCT and could represent a therapeutic
      target. Analyses of human GCT samples showed an increase in protein levels of
      mTOR and its downstream effectors RPS6KB1, RPS6, eIF4B and PPARG relative to
      normal granulosa cells, suggestive of an increase in mTOR pathway activity and
      increased translational activity and/or protein stability. We next sought to
      evaluate mTOR as a GCT therapeutic target using the Pten  (tm1Hwu/tmiHwu);Ctnnb1 
      (tm1Mmt/+);Amhr2  (tm3(cre)Bhr/+) (PCA) mouse model, in which mTOR, RPS6KB1,
      eIF4B and PPARG are upregulated in tumor cells in a manner similar to human GCT.
      Treatment of PCA mice with the mTOR-specific inhibitor everolimus reduced tumor
      growth rate (1.5-fold; P < 0.05) and also reduced total tumor burden (4.7-fold; P
      < 0.05) and increased survival rate (78 versus 44% in the vehicle group) in a PCA
      surgical model of GCT peritoneal carcinomatosis. Everolimus decreased tumor cell
      proliferation and tumor cell volume relative to controls (P < 0.05), whereas
      apoptosis was unaffected. Phosphorylation of RPS6KB1 and RPS6 were decreased (P <
      0.05) by everolimus, but RPS6KB1, RPS6, eIF4B and PPARG expressions were not
      affected. These results suggest that mTOR is a valid and clinically useful
      pharmacological target for the treatment of GCT, although its inhibition does not
      reverse all consequences of aberrant PI3K/AKT signaling in the PCA model.

PMID- 22871498
TI  - Development and validation of a new histological score for pediatric non
      alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Pediatric non-alcoholic fatty liver disease (NAFLD) may
      present with a distinct histopathological pattern characterized by the presence
      of predominant portal-based injury and portal inflammation (PI). We aimed at
      developing a new grading score for pediatric NAFLD to be used in clinical trials
      that takes into account the presence of PI and the weight of histological
      features. METHODS: Our training set consisted of 203 children with biopsy-proven
      NAFLD. The diagnosis of non-alcoholic steatohepatitis (NASH) was based on Brunt's
      criteria. Histological features were scored: steatosis (0-3), lobular
      inflammation (0-3), ballooning (0-2), and PI (0-2). Logistic regression analysis
      was performed to apply weight to each feature. The new score was called the
      Pediatric NAFLD Histological Score or PNHS. The validation set consisted of 100
      children with NAFLD. RESULTS: The mean age of the initial cohort was 12.4 +/- 3.4
      years and significant fibrosis (fibrosis stage >= 2) was present in 26 patients
      (12.8%). NASH was diagnosed in 135 patients with a mean NAS of 4.5 +/- 1.4. The
      mean PNHS in the NASH group was 89 +/- 20.5 compared to 21.9 +/- 24.5 in the "not
      NASH" group, p<0.001. PNHS correlated with the presence of NASH according to the
      pathologist's diagnosis, better than the NAFLD activity score (NAS), p=0.011. The
      area under the ROC curve (AUC) for the diagnosis of NASH was 0.96 for PNHS.
      Similar findings were observed in the validation set with an AUC of 0.94.
      CONCLUSIONS: PNHS may be used for histological grading of pediatric NAFLD with
      excellent correlation with the presence of NASH.

PMID- 22871497
TI  - Radioguided occult lesion localisation (ROLL) in breast-conserving surgery after
      neoadjuvant chemotherapy.
AB  - BACKGROUND: An important benefit of neoadjuvant chemotherapy, as compared to
      adjuvant chemotherapy, in breast cancer patients is down staging of the primary
      tumour, which allows for more breast-conserving surgery. When a tumour becomes
      non-palpable after this down staging, precise localisation of the original tumour
      bed is crucial to be able to perform breast-conserving surgery. Radioguided
      Occult Lesion Localisation with (99m)Technetium (ROLL-(99m)Tc) is commonly used
      to perform breast-conserving surgery in patients with non-palpable breast
      tumours. We modified this technique to use it in the neoadjuvant setting. The
      present analysis was performed to assess its feasibility and analyse the number
      of patients in which a mastectomy was correctly withheld using this technique.
      METHODS: A retrospective analysis was performed for all patients who were treated
      with neoadjuvant chemotherapy between 2007 and 2010 in our institute and
      underwent breast-conserving surgery with the ROLL-(99m)Tc technique afterwards.
      The status of the margins and the weight of the resected specimen were assessed.
      RESULTS: The median weight of the resected specimen in these 83 patients was 53 g
      (range: 11-204 g). Eleven of the 58 patients with residual disease revealed
      positive margins at pathological examination. However, in only 5 of those 11
      patients a secondary mastectomy was indicated. This means that in 94% of all
      included patients a mastectomy was correctly withheld. CONCLUSION: The ROLL
      (99m)Tc technique is a feasible technique that can be used to perform breast
      conserving surgery after neoadjuvant chemotherapy in a carefully selected group
      of patients.

PMID- 22871499
TI  - Prevalence and risk factors of non-alcoholic fatty liver disease in the elderly:
      results from the Rotterdam study.
AB  - BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD)
      appears to increase with age. However, limited data are available concerning the
      prevalence of NAFLD in the elderly. Our aim was to determine the prevalence and
      risk factors of NAFLD in an elderly population. METHODS: This study was based on
      participants in the population-based Rotterdam Study. Each participant was
      interviewed and had a clinical examination at the research center, including a
      fasting blood collection, liver ultrasonography, and anthropometric assessment.
      Ordinal and logistic regression analysis was used to assess associations between
      covariables and (severity of) NAFLD. RESULTS: Data from 2811 participants (mean
      age 76.4 +/- 6.0 years) were analyzed. The prevalence of NAFLD was 35.1%. The
      prevalence of NAFLD decreased with advancing age (p<0.001). In logistic
      regression analysis, age (OR 0.97; 95% CI 0.95-0.99; p<0.001), total physical
      activity level (OR 0.98, 95% CI 0.96-0.99; p=0.005), pack years of smoking (OR
      1.01, 95% CI 1.00-1.01; p=0.02), waist circumference >88 cm for women and > 102
      cm for men (OR 4.89; CI 4.00-5.96; p<0.001), fasting glucose >= 100 mg/dl or drug
      treatment for elevated blood glucose (OR 2.11, 95% CI 1.72-2.59; p<0.001), blood
      pressure >= 130/85 mmHg or drug treatment for elevated blood pressure (OR 1.80,
      95% CI 1.08-3.01; p=0.03), and triglycerides >= 150 mg/dl or treatment with serum
      lipid reducing agents (OR 1.56, 95% CI 1.28-1.91; p<0.001) were associated with
      NAFLD. CONCLUSIONS: NAFLD is common in the elderly, although the prevalence
      decreases with advancing age. Further studies are warranted exploring potential
      factors contributing to this apparent positive selection effect in the elderly.

PMID- 22871500
TI  - Acute exacerbation and reactivation of chronic hepatitis C virus infection in
      cancer patients.
AB  - BACKGROUND & AIMS: Data on acute exacerbation and reactivation of chronic
      hepatitis C virus (HCV) infection following chemotherapy are very limited. We
      sought to characterize the episodes of acute exacerbation and viral reactivation
      of HCV infection in cancer patients. METHODS: The medical records of HCV-infected
      patients seen at our institution (2008-2009) were analyzed retrospectively. Acute
      exacerbation was defined as greater than 3-fold increase in serum level of
      alanine aminotransferase, and viral reactivation as >= 1 log(10) IU/ml increase
      of HCV viral load following chemotherapy. RESULTS: Acute exacerbation occurred in
      33 (11%) of 308 patients with proven HCV infection. Patients with acute
      exacerbation more often had underlying hematological malignancies (73% vs. 29%;
      p<0.001) and lymphopenia (6% vs. 0%; p=0.01) than patients without it. In
      multivariate analysis, underlying hematological malignancies (p=0.02; odds ratio,
      3.2; 95% confidence interval, 1.2-8.7) and use of rituximab (p=0.004; odds ratio,
      4.2; 95% confidence interval, 1.6-10.9) were associated with acute exacerbation.
      Patients with acute exacerbation received higher median cumulative dose of
      rituximab than those without exacerbation. Discontinuation of chemotherapy due to
      liver dysfunction was more common in patients with acute exacerbation than in
      patients without it (45% vs. 11%; p<0.001). Eight (36%) of 22 patients with known
      pre- and post-chemotherapy viral load had viral reactivation. CONCLUSIONS: Acute
      exacerbation and reactivation of chronic HCV infection occur often after
      chemotherapy. Liver dysfunction can lead to discontinuation of potentially life
      saving chemotherapy in nearly one-half of the patients with exacerbation of HCV
      infection.

PMID- 22871501
TI  - Vitamin D for your patients with chronic hepatitis C?
AB  - Vitamin D is increasingly becoming recognized as an important physiological
      regulator with pleiotropic functions outside of its classical role in skeletal
      homeostasis. A growing body of clinical evidence highlights the prevalence and
      risks of vitamin D deficiency in patients suffering from chronic hepatitis C
      infection, and vitamin D supplementation has been proposed as an adjunct to
      current standards of care. This review considers the experimental evidence for
      the anti-inflammatory, antifibrotic and antiviral effects of vitamin D, and
      discusses the therapeutic potential of vitamin D supplementation to protect
      against liver disease progression and improve responses to treatment.

PMID- 22871502
TI  - Response rate and clinical outcome of HCC after first and repeated cTACE
      performed "on demand".
AB  - BACKGROUND & AIMS: Aim of the study was to assess the clinical impact of
      conventional transarterial chemoembolization (cTACE) repeated "on demand" on HCC
      outcome. Outcome measures were: response rate to first and repeated cTACE,
      recurrence rates and overall survival. METHODS: The outcome of 151 consecutive
      HCC patients submitted to a first cTACE from January 2004 to December 2005 was
      retrospectively analyzed. RESULTS: Complete radiological response (CR) was
      observed in 72/151 (48%), 34/60 (52%) and 12/22 (55%) patients after first,
      second and third cTACE, respectively. Recurrence rates at 6 and 12months were 37%
      and 61% after the first cTACE, and 40% and 59% after the second cTACE,
      respectively. Patients not achieving CR or with a recurrence after CR not treated
      with curative therapies were 94 and 84 after first and second cTACE,
      respectively. Of these, 60/94 (64%) and 22/84 (26%) were submitted to a second
      and third cTACE, respectively. Median overall survival was 32.0months but
      25.0months excluding transplanted patients. Factors at the time of first cTACE
      associated with overall shorter survival at multivariate analysis were higher
      bilirubin, higher AFP and not achieving CR. CONCLUSIONS: CR and recurrence rates
      after first and second cTACE were similar. About 64% of patients were submitted
      to second cTACE, while only few patients (26%) were submitted to third cTACE
      using an "on demand" policy. These figures may be also useful for planning trials
      for the evaluation of the efficacy of repeated TACE vs. TACE combined with
      adjuvant treatments or vs. systemic treatments.

PMID- 22871503
TI  - Identifying opportunities to improve management of autoimmune hepatitis:
      evaluation of drug adherence and psychosocial factors.
AB  - BACKGROUND & AIMS: Recognizing the importance of adherence to therapy in
      autoimmune hepatitis (AIH) is critical for patient care and avoidance of
      unnecessary intervention. The influence of psychosocial factors on treatment
      adherence needs better understanding and prominence. We sought to determine the
      association between anxiety, depressive symptoms, and avoidant relationship style
      on self-reported immunosuppressant medication adherence and treatment response in
      patients with AIH. METHODS: Fifty two patients with AIH were assessed using the
      Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the
      Experiences in Close Relationship Scale (ECR) and a visual analogue scale to
      measure self-reported adherence. Laboratory markers of adherence and
      immunosuppressant treatment response were recorded. Chi-square Fisher's exact or
      Wilcox rank sum tests were used for comparison between groups. RESULTS: Treatment
      responders compared to non-responders were older (p=0.035), had normal or mild
      score ranges for anxiety and depression (p=0.025) and were significantly more
      likely to report >80% treatment adherence (p=0.007). Non-responders had higher
      anxiety symptoms (p=0.025), and significantly higher ECR-avoidance scores
      (p=0.023), suggestive of a tendency towards a more avoidant relationship style.
      CONCLUSIONS: We formally document that patients with AIH who have higher
      depressive and anxiety symptoms and avoidant relationship styles are more likely
      to be non-adherent to AIH therapy. We reiterate the need for early recognition
      and treatment of anxiety and depression in patients with AIH, stress the need for
      treatment adherence and highlight the need for formal evaluation of these factors
      in trials of therapy targeting apparent treatment non-responders.

PMID- 22871504
TI  - Metabolic engineering of Escherichia coli for the production of 1-propanol.
AB  - An engineered Escherichia coli strain that produces 1-propanol under aerobic
      condition was developed based on an L-threonine-overproducing E. coli strain.
      First, a feedback resistant ilvA gene encoding threonine dehydratase was
      introduced and the competing metabolic pathway genes were deleted. Further
      engineering was performed by overexpressing the cimA gene encoding citramalate
      synthase and the ackA gene encoding acetate kinase A/propionate kinase II,
      introducing a modified adhE gene encoding an aerobically functional AdhE, and by
      deleting the rpoS gene encoding the stationary phase sigma factor. Fed-batch
      culture of the final engineered strain harboring pBRthrABC-tac-cimA-tac-ackA and
      pTacDA-tac-adhE(mut) allowed production of 10.8 g L(-1) of 1-propanol with the
      yield and productivity of 0.107 g g(-1) and 0.144 g L(-1) h(-1), respectively,
      from 100 g L(-1) of glucose, and 10.3 g L(-1) of 1-propanol with the yield and
      productivity of 0.259 g g(-1) and 0.083 g L(-1) h(-1), respectively, from 40 g L(
      1) glycerol.

PMID- 22871505
TI  - Increased lysine production by flux coupling of the tricarboxylic acid cycle and
      the lysine biosynthetic pathway--metabolic engineering of the availability of
      succinyl-CoA in Corynebacterium glutamicum.
AB  - In this study, we demonstrate increased lysine production by flux coupling using
      the industrial work horse bacterium Corynebacterium glutamicum, which was
      mediated by the targeted interruption of the tricarboxylic acid (TCA) cycle at
      the level of succinyl-CoA synthetase. The succinylase branch of the lysine
      production pathway functions as the bridging reaction to convert succinyl-CoA to
      succinate in this aerobic bacterium. The mutant C. glutamicum DeltasucCD showed a
      60% increase in the yield of lysine when compared to the advanced lysine producer
      which was used as parent strain. This mutant was highly vital and exhibited only
      a slightly reduced specific growth rate. Metabolic flux analysis with (13)C
      isotope studies confirmed that the increase in lysine production was mediated by
      pathway coupling. The novel strain exhibited an exceptional flux profile, which
      was closer to the optimum performance predicted by in silico pathway analysis
      than to the large set of lysine-producing strains analyzed thus far. Fluxomics
      and transcriptomics were applied as further targets for next-level strain
      engineering to identify the back-up mechanisms that were activated upon deletion
      of the enzyme in the mutant strain. It seemed likely that the cells partly
      recruited the glyoxylate shunt as a by-pass route. Additionally, the alpha
      ketoglutarate decarboxylase pathway emerged as the potential compensation
      mechanism. This novel strategy appears equally promising for Escherichia coli,
      which is used in the industrial production of lysine, wherein this bacterium
      synthesizes lysine exclusively by succinyl-CoA activation of pathway
      intermediates. The channeling of a high flux pathway into a production pathway by
      pathway coupling is an interesting metabolic engineering strategy that can be
      explored to optimize bio-production in the future.

PMID- 22871506
TI  - The psychometric properties of five Professional Identity measures in a sample of
      nursing students.
AB  - BACKGROUND: Researchers have yet to fully explore and adequately measure
      Professional Identity (PI) in nursing. OBJECTIVES: This paper aims to examine the
      psychometrics of five measures of PI and compare these results in first and third
      year nursing students. As a consequence of utilising multiple self-assessed
      survey tools this study also examines common methods bias. DESIGN: The study
      utilised an on-line survey to gather responses from nursing students. METHODS:
      The pilot study examined the validity and reliability of the five measures while
      investigating the potential for common methods bias. RESULTS: All five measures
      tested demonstrated poorer psychometric properties or model fits for this sample
      than those reported by their original authors. One measure demonstrated a small
      mean score increase from first to third year, while all others revealed a fall
      from first to third year, although these were not significant. Harman's tests
      performed on all scales were negative for common methods bias. CONCLUSIONS: A
      psychometrically strong measure of PI was not determined however, this may relate
      to the sample size in this pilot study. The fall of PI from first to third year
      and the factors that influence such change may have implications for the
      recruitment and retention of nurses.

PMID- 22871507
TI  - Air pollution exposure and telomere length in highly exposed subjects in Beijing,
      China: a repeated-measure study.
AB  - BACKGROUND: Ambient particulate matter (PM) exposure has been associated with
      short- and long-term effects on cardiovascular disease (CVD). Telomere length
      (TL) is a biomarker of CVD risk that is modified by inflammation and oxidative
      stress, two key pathways for PM effects. Whether PM exposure modifies TL is
      largely unexplored. OBJECTIVES: To investigate effects of PM on blood TL in a
      highly-exposed population. METHODS: We measured blood TL in 120 blood samples
      from truck drivers and 120 blood samples from office workers in Beijing, China.
      We measured personal PM(2.5) and Elemental Carbon (EC, a tracer of traffic
      particles) using light-weight monitors. Ambient PM(10) was obtained from local
      monitoring stations. We used covariate-adjusted regression models to estimate
      percent changes in TL per an interquartile-range increase in exposure. RESULTS:
      Covariate-adjusted TL was higher in drivers (mean=0.87, 95%CI: 0.74; 1.03) than
      in office workers (mean=0.79, 95%CI: 0.67; 0.93; p=0.001). In all participants
      combined, TL increased in association with personal PM(2.5) (+5.2%, 95%CI: 1.5;
      9.1; p=0.007), personal EC (+4.9%, 95%CI: 1.2; 8.8; p=0.01), and ambient PM(10)
      (+7.7%, 95%CI: 3.7; 11.9; p<0.001) on examination days. In contrast, average
      ambient PM(10) over the 14 days before the examinations was significantly
      associated with shorter TL (-9.9%, 95%CI: -17.6; -1.5; p=0.02). CONCLUSIONS:
      Short-term exposure to ambient PM is associated with increased blood TL,
      consistent with TL roles during acute inflammatory responses. Longer exposures
      may shorten TL as expected after prolonged pro-oxidant exposures. The observed TL
      alterations may participate in the biological pathways of short- and long-term PM
      effects.

PMID- 22871508
TI  - Prevalence, characteristics, and factors associated with chronic pain with and
      without neuropathic characteristics in Sao Luis, Brazil.
AB  - CONTEXT: Chronic pain (CP) with and without neuropathic characteristics is a
      public health problem. This is the first population-based study in South America,
      and the third in the world, to use the Douleur Neuropathique 4 Questions (DN4)
      tool in epidemiologic studies. OBJECTIVES: The objectives were to estimate the
      prevalence and associated factors of CP with and without neuropathic
      characteristics in Sao Luis, Brazil. METHODS: We surveyed 1597 people. The DN4
      questionnaire was applied. Poisson regression was used to analyze the risk
      factors. RESULTS: The prevalence of CP was 42%, and 10% had CP with neuropathic
      characteristics (CPNC). The results showed that female sex and age >=30 years
      were associated with an increased prevalence of CP (P<0.001) and education >=12
      years with a reduction in the prevalence of CP. The sensations listed in the DN4
      were more common in people with CPNC and most frequent were pins and needles
      (87.9%). The cephalic region (36%) and limbs (51%) were the locations most
      affected. Most respondents felt pain between six months and four years (51.6%),
      with daily frequency (45%). Pain intensity, the impediments caused by pain, and
      sadness were more prevalent in people who had CPNC (P<0.001). Health status was
      regular for most, 50.9% did not know the cause of their pain, 64.1% used drugs,
      and only 7% had consulted with a pain specialist. Dissatisfaction with treatment
      was reported by 55%. CONCLUSION: CP with and without neuropathic characteristics
      is a public health problem in Brazil, with high prevalence and great influence on
      people's daily lives.

PMID- 22871509
TI  - A systematic evaluation of content, structure, and efficacy of interventions to
      improve patients' self-management of cancer pain.
AB  - CONTEXT: Cancer pain continues to be extensively undertreated, despite
      established guidelines. Although the efficacy of interventions that support
      patients' self-management of cancer pain has been demonstrated in several
      studies, the most effective components of these interventions remain unknown.
      OBJECTIVES: The purpose of this review of experimental and quasi-experimental
      studies was to systematically describe the structure and content components, as
      well as the efficacy of various components, of interventions designed to improve
      patients' self-management of cancer pain. METHODS: A systematic review of the
      literature was done that supplemented the 2009 meta-analysis of Bennett et al.
      Intervention components were categorized using content analysis. The intervention
      components were compared based on their calculated largest effect sizes (ESs)
      within each study (i.e., Hedges G(u) for between-group differences in pain
      intensity scores). RESULTS: Based on 34 publications (i.e., 24 interventions),
      seven structure and 16 content components were identified. In 11 studies with
      statistically significant ESs, the largest ES within each study ranged from -1.87
      to -0.44, which represented clinically meaningful effects. No single component
      was found to have a discernable influence on ES. CONCLUSION: This analysis
      provides researchers and clinicians with a detailed overview of the various
      structural and content components, as well as various combinations that were
      tested in intervention studies to improve cancer pain management. However,
      because of a variety of limitations, the most efficacious intervention components
      or combination of components remain to be determined in future studies.

PMID- 22871510
TI  - Emergencies in patients with advanced cancer followed at home.
AB  - CONTEXT: Patients with advanced cancer stay at home for most of their time, and
      acute problems may occur during home care. Caregivers may call medical services
      for an emergency, which can result in patients being admitted to the hospital. No
      data exist on emergencies in patients followed by a home care team. OBJECTIVES:
      The aim of this multicenter prospective study was to assess the frequency,
      reasons for, and subsequent course of emergency calls for patients followed at
      home by a palliative care team. METHODS: A consecutive sample of patients
      admitted to home care programs was surveyed for a period of seven months.
      Epidemiological data, and characteristics of emergency calls and outcomes, as
      well as environmental situations were recorded. RESULTS: Six hundred eighty-nine
      patients were surveyed; 118 patients (17.1% of the total number of patients
      surveyed) made one emergency call, 23 made two calls, and four made three calls
      for a total number of 176 emergency calls. The mean age was 71 years (standard
      deviation [SD] 13), and the mean Karnofsky status the day before the emergency
      call was 38 (SD 14). The mean time from admission to the first emergency call was
      38.4 days (SD 67), and the mean time from the first emergency call to death was
      17.5 days (SD 41.5). No differences were found for age, diagnosis, gender,
      duration of assistance, and survival between patients making emergency calls and
      those who did not make a call during an emergency. Twenty-three patients were
      managed by phone, and 122 were visited at home for the emergency. Calls were
      prevalently recorded on weekdays and were primarily made by relatives. The most
      frequent reasons for calling were dyspnea, pain, delirium, and loss of
      consciousness. Calls were considered justified by home care physicians in most
      cases. The mean number of relatives present during the emergency home visit was
      2.2 (SD 1.5). The intervention was mainly pharmacological and considered
      satisfactory in the majority of cases. CONCLUSION: Emergency calls are relatively
      frequent in patients followed at home by a palliative care team. Phone
      consultation or intervention at home may avoid inappropriate hospital admission.

PMID- 22871511
TI  - To drain or not to drain: an evidence-based approach to palliative procedures for
      the management of malignant pleural effusions.
AB  - Malignant pleural effusions are often symptomatic and diagnosed late in the
      course of cancer. The optimal management strategy is controversial and includes
      both invasive and non-invasive strategies. Practitioners have the option of
      invasive procedures such as intermittent drainage or more permanent catheter
      drainage to confirm malignancy and to palliate symptoms. Because these effusions
      are often detected late in the course of disease in patients who may have limited
      life expectancy, procedural management may be associated with harms that outweigh
      benefits. We performed a literature review to examine the available evidence for
      catheter drainage of malignant pleural effusions in advanced cancer and reviewed
      alternative management strategies for the management of dyspnea. We provide a
      clinical case within the context of the research evidence for invasive and non
      invasive management strategies. Our intent is to help inform decision making of
      patients and families in collaboration with their health care practitioners and
      interventionists by weighing the risks and benefits of catheter drainage versus
      alternative medical management strategies for malignant pleural effusions.

PMID- 22871512
TI  - Life is uncertain. death is certain. Buddhism and palliative care.
AB  - It is part of a palliative care assessment to identify patients' spiritual needs.
      According to Buddhism, suffering is inherent to all human beings. Advice on how
      suffering can be reduced in the course of serious illness might be helpful to
      patients with incurable and progressive diseases. Palliative care could benefit
      from Buddhist insights in the form of compassionate care and relating death to
      life. Buddhist teachings may lead to a more profound understanding of incurable
      diseases and offer patients the means by which to focus their minds while dealing
      with physical symptoms and ailments. This might not only be beneficial to
      followers of Buddhism but to all patients.

PMID- 22871515
TI  - "One more time" 5-ASA retrial after a glucocorticosteroid induced remission in
      moderate to severe ulcerative colitis: a prospective community practice
      experience.

PMID- 22871516
TI  - Design and synthesis of molecularly imprinted polypyrrole based on nanoreactor
      SBA-15 for recognition of ascorbic acid.
AB  - Molecular imprinting is an attractive technique for preparing mimics of natural
      and biological receptors. Nevertheless, molecular imprinting for aqueous systems
      remains a challenge due to the hydrogen bonding between templates and functional
      monomers destroyed in the bulk water. The hydrogen bonding between templates and
      monomers are the most crucial factor governing recognition, particularly in non
      covalent molecularly imprinted polymers. Using mesoporous materials for molecular
      imprinting is an effective approach to overcome this barrier and to remove the
      limitations of the traditional molecularly imprinted polymers which include
      incomplete template removal, small binding capacity, slow mass transfer, and
      irregular materials shape. Here, SBA-15 was used as a mesoporous silica material
      for synthesis of molecularly imprinted polypyrrole. The pyrrole monomers and
      template molecules were immobilized onto the SBA-15 hexagonal channels, and then
      polymerization occurred. The resulting nanocomposites were characterized by
      Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM) methods. In batch rebinding tests, the
      imprinted nanocomposites reached saturated adsorption within 100min and exhibited
      significant specific recognition toward the ascorbic acid (AA) with high
      adsorption capacity (83.7mg g(-1)). To further illustrate the recognition
      property of the imprinted nanocomposites, binary competitive and non-competitive
      adsorption experiments were performed with ascorbic acid, dopamine, paracetamol
      and epinephrine. The imprinting factors for these compounds in non-competitive
      adsorption experiments were 3.2, 1.5, 1.4 and 1.3, respectively. The results
      showed that the imprinted nanocomposites exhibited significant adsorption
      selectivity for the ascorbic acid against the related compounds.

PMID- 22871517
TI  - Distance from source of reward as a marker for extinction-induced "despair":
      modulation by the antidepressants clomipramine and citalopram.
AB  - Despair-related withdrawal behaviors are common symptoms of major depression (MD)
      and can be ascribed to a loss or absence of former rewarding events. Extinction
      of negatively reinforced escape behavior in the Morris Water Maze has been shown
      to induce despair-like behavior. A new animal model of depressive-like behavior
      is based on the extinction of positively reinforced behavior, which was shown to
      induce spatial avoidance of the former source of reward and biting of the
      operandum. Treatment with antidepressants attenuated these extinction-induced
      behaviors, suggesting that they reflect a depressive-like state. Here we present
      a methodological variation of this depression model. We employed an elongated
      operant chamber rather than a two-compartment procedure with the intent to
      establish a flowing gradient of withdrawal from the source of reward, rather than
      an all-or-none binary measure. Furthermore, instead of employing extinction of
      lever-pressing behavior, we applied a cued fixed-time food-delivery schedule.
      Sixty adult male Wistar rats (n=12/group) were trained to receive a food reward
      after appearance of a cue-light (fixed interval 90s) in an elongated Skinner-box
      of 72 cm length. Prior to extinction, the animals were treated for 9 days with
      either 7.5 or 10mg/kg of the tricyclic antidepressant clomipramine, 7.5 or
      10mg/kg of the selective serotonin reuptake inhibitor (SSRI) citalopram or
      vehicle. Subsequent testing in an open field was carried out to investigate
      potential effects of the antidepressants on locomotor- and anxiety-like behavior.
      An overall increase in distance from the feeder and biting behavior was found
      over the course of the extinction trials. Both, citalopram and clomipramine
      decreased the distance from the pellet feeder during the initial extinction
      trials compared to the vehicle-treated group. The attenuation of withdrawal
      behavior by the antidepressants supports the hypothesis that avoidance/withdrawal
      behavior during extinction trials can serve as a marker for extinction-induced
      depression and suggests the utility of this paradigm as a rodent model of
      depression.

PMID- 22871514
TI  - Membrane-initiated actions of estradiol that regulate reproduction, energy
      balance and body temperature.
AB  - It is well known that many of the actions of estrogens in the central nervous
      system are mediated via intracellular receptor/transcription factors that
      interact with steroid response elements on target genes. However, there now
      exists compelling evidence for membrane estrogen receptors in hypothalamic and
      other brain neurons. But, it is not well understood how estrogens signal via
      membrane receptors, and how these signals impact not only membrane excitability
      but also gene transcription in neurons. Indeed, it has been known for sometime
      that estrogens can rapidly alter neuronal activity within seconds, indicating
      that some cellular effects can occur via membrane delimited events. In addition,
      estrogens can affect second messenger systems including calcium mobilization and
      a plethora of kinases to alter cell signaling. Therefore, this review will
      consider our current knowledge of rapid membrane-initiated and intracellular
      signaling by estrogens in the hypothalamus, the nature of receptors involved and
      how they contribute to homeostatic functions.

PMID- 22871518
TI  - Similarities and differences between the brain networks underlying allocentric
      and egocentric spatial learning in rat revealed by cytochrome oxidase
      histochemistry.
AB  - The involvement of different brain regions in place- and response-learning was
      examined using a water cross-maze. Rats were trained to find the goal from the
      initial arm by turning left at the choice point (egocentric strategy) or by using
      environmental cues (allocentric strategy). Although different strategies were
      required, the same maze and learning conditions were used. Using cytochrome
      oxidase histochemistry as a marker of cellular activity, the function of the 13
      diverse cortical and subcortical regions was assessed in rats performing these
      two tasks. Our results show that allocentric learning depends on the recruitment
      of a large functional network, which includes the hippocampal CA3, dentate gyrus,
      medial mammillary nucleus and supramammillary nucleus. Along with the striatum,
      these last three structures are also related to egocentric spatial learning. The
      present study provides evidence for the contribution of these regions to spatial
      navigation and supports a possible functional interaction between the two memory
      systems, as their structural convergence may facilitate functional cooperation in
      the behaviours guided by more than one strategy. In summary, it can be argued
      that spatial learning is based on dynamic functional systems in which the
      interaction of brain regions is modulated by task requirements.

PMID- 22871519
TI  - Antinociceptive evaluation of ceftriaxone and minocycline alone and in
      combination in a neuropathic pain model in rat.
AB  - Glutamate homeostasis and microglia activation play an important role in the
      development and maintenance of neuropathic pain. So far, there has been
      insufficient data on the relationship between glutamate transporters and
      cytokines in neuropathic pain. This investigation was designed to evaluate the
      interaction between co-administration of ceftriaxone, a specific GLT1 activator
      and minocycline, a specific microglia inhibitor, on the mechanical and cold
      allodynia of chronic constriction injury model (CCI) in rats. Moreover,
      alteration of the spinal concentration of proinflammatory cytokines, tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was studied.
      Ceftriaxone (100, 150 and 200mg/kg, i.p.) and minocycline (25, 50 and 100mg/kg,
      i.p.) were administered either alone or in combination for 7 days. Gabapentin
      (100mg/kg, i.p.) was selected as a reference drug. Behavioral evaluations were
      performed 1 day before and on days 3, 5, 7, 10 and 14 after surgery. Each of
      drugs produced a dose-dependent reversal of the neuropathic pain behaviors. Area
      under the curve (AUC) of combination therapy revealed that minocycline
      potentiated cold and mechanical antiallodynic effects of ceftriaxone. TNF-alpha
      and IL-1beta increased in the spinal cord of CCI animals on days 3, 7 and 14 post
      surgery. Production of studied cytokines was significantly attenuated after
      treatment with ceftriaxone alone and in combination with minocycline compared
      with control group. It is suggested that combination of these classes of drugs
      would be a promising approach for treatment of chronic neuropathic pain.

PMID- 22871520
TI  - Effects of cross-modal selective attention on the sensory periphery: cochlear
      sensitivity is altered by selective attention.
AB  - There is increasing evidence that alterations in the focus of attention result in
      changes in neural responding at the most peripheral levels of the auditory
      system. To date, however, those studies have not ruled out differences in task
      demands or overall arousal in explaining differences in responding across
      intermodal attentional conditions. The present study sought to compare changes in
      the response of cochlear outer hair cells, employing distortion product
      otoacoustic emissions (DPOAEs), under different, balanced conditions of
      intermodal attention. DPOAEs were measured while the participants counted
      infrequent, brief exemplars of the DPOAE primary tones (auditory attending), and
      while counting visual targets, which were instances of Gabor gradient phase
      shifts (visual attending). Corroborating an earlier study from our laboratory,
      the results show that DPOAEs recorded in the auditory-ignoring condition were
      significantly higher in overall amplitude, compared with DPOAEs recorded while
      participants attended to the eliciting primaries; a finding in apparent
      contradiction with more central measures of intermodal attention. Also consistent
      with our previous findings, DPOAE rapid adaptation, believed to be mediated by
      the medial olivocochlear efferents (MOC), was unaffected by changes in intermodal
      attention. The present findings indicate that manipulations in the conditions of
      attention, through the corticofugal pathway, and its last relay to cochlear outer
      hair cells (OHCs), the MOC, alter cochlear sensitivity to sound. These data also
      suggest that the MOC influence on OHC sensitivity is composed of two independent
      processes, one of which is under attentional control.

PMID- 22871521
TI  - Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid
      induced neurodegeneration through the activation of nuclear factor-erythroid 2
      related factor-2 signalling pathway.
AB  - Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediated regulation of
      cellular antioxidant production and the anti-inflammatory mechanism play an
      important role in neuroprotection against neurodegenerative diseases. Naringin a
      citrus flavonone, has been reported to possess neuroprotective effect against
      Huntington's disease, and other neurodegenerative disorders, however the
      mechanisms underlying its beneficial effects on 3-nitropropionic acid (3-NP)
      induced neurodegeneration are poorly defined. The objective of the present study
      was to investigate the neuroprotective role of naringin and delineate the
      mechanism of action on 3-NP-induced neurodegeneration. Rats were injected with 3
      NP (10mg/kg body weight/day, i.p.) for 2 weeks to develop neurodegeneration,
      while naringin (80 mg/kg body weight/day, orally) was administered throughout the
      experimental period, 1h prior to 3-NP exposure. Thereafter rats were euthanized
      for biochemical, histological, and molecular studies. Treatment with naringin
      ameliorated the reduced glutathione/oxidized glutathione ratio with concomitant
      decrease in the levels of hydroxyl radical, hydroperoxide and nitrite in 3-NP
      induced rats. Nissl staining and transmission electron microscopic studies showed
      that naringin modulated 3-NP-induced histological changes. Naringin induces
      NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutathione S-transferase P1
      and gamma-glutamylcysteine ligase mRNA expressions through the activation of Nrf2
      and decreased the expressions of pro-inflammatory mediators like tumour necrosis
      factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. These results
      indicate that naringin might be beneficial in mitigating 3-NP-induced
      neurodegeneration through the enhancement of phase II and antioxidant gene
      expressions via Nrf2 activation; thereby modulating the oxidative stress and
      inflammatory responses.

PMID- 22871522
TI  - Odor-evoked activity in the mouse lateral entorhinal cortex.
AB  - The entorhinal cortex is a brain area with multiple reciprocal connections to the
      hippocampus, amygdala, perirhinal cortex, olfactory bulb and piriform cortex. As
      such, it is thought to play a large role in the olfactory memory process. The
      present study is the first to compare lateral entorhinal and anterior piriform
      cortex odor-evoked single-unit and local field potential activity in mouse.
      Recordings were made in urethane-anesthetized mice that were administered a range
      of three pure odors and three overlapping odor mixtures. Results show that
      spontaneous as well as odor-evoked unit activity was lower in lateral entorhinal
      versus piriform cortex. In addition, units in lateral entorhinal cortex were
      responsive to a more restricted set of odors compared to piriform. Conversely,
      odor-evoked power change in local field potential activity was greater in the
      lateral entorhinal cortex in the theta band than in piriform. The highly odor
      specific and restricted firing in lateral entorhinal cortex suggests that it may
      play a role in modulating odor-specific, experience- and state-dependent
      olfactory coding.

PMID- 22871523
TI  - Visual acuity in the short-tailed opossum (Monodelphis domestica).
AB  - Monodelphis domestica (short-tailed opossum) is an emerging animal model for
      studies of neural development due to the extremely immature state of the nervous
      system at birth and its subsequent rapid growth to adulthood. Yet little is known
      about its normal sensory discrimination abilities. In the present investigation,
      visual acuity was determined in this species using the optokinetic test (OPT),
      which relies on involuntary head tracking of a moving stimulus and can be easily
      elicited using a rotating visual stimulus of varying spatial frequencies. Using
      this methodology, we determined that the acuity of Monodelphis is 0.58 cycles per
      degree (cpd), which is similar to the acuity of rats using the same methodology,
      and higher than in mice. However, acuity in the short-tailed opossum is lower
      than in other marsupials. This is in part due to the methodology used to
      determine acuity, but may also be due to differences in diel patterns, lifestyle
      and phylogeny. We demonstrate that for the short-tailed opossum, the OPT is a
      rapid and reliable method of determining a baseline acuity and can be used to
      study enhanced acuities due to cortical plasticity.

PMID- 22871525
TI  - Determinants of receiving mental health care for depression in older adults.
AB  - BACKGROUND: Major Depressive Disorder (MDD) is common among elderly people.
      However, it appears that only a minority receives treatment. This study aims to
      identify and analyse the factors that determine whether elderly people with
      depressive disorders have contact with health care professionals for mental
      problems. METHOD: Cross-sectional analysis of cohort data collected in the
      Netherlands Study of Depression in Older persons (NESDO) and the Netherlands
      Study of Depression and Anxiety (NESDA) among 167 respondents aged >=55 with a
      depressive disorder as indicated by the CIDI. Contacts for mental health problems
      during the past six months (TiC-P), and indicators of predisposing, enabling, and
      objective need factors were assessed by interview. RESULTS: Of the total sample,
      70% had contact for mental health problems, almost entirely within primary care
      (62%). The odds of having contact increased with advancing age; for respondents
      born in the Netherlands; for those who felt less lonely; and for those with a
      higher household income. LIMITATIONS: Our study is based on base-line interviews
      and thus has a cross-sectional character. Therefore, causal conclusions cannot be
      drawn. Furthermore, we studied the respondents' perception whether mental health
      care was received. CONCLUSIONS: The contact rate for mental health problems is
      high. Health care professionals should be aware that having contact is not
      associated with a higher objective need, but rather with increasing age, being
      Dutch-born, being less lonely and having a higher household income.

PMID- 22871526
TI  - Changes in commonly used methods of suicide in England and Wales from 1901-1907
      to 2001-2007.
AB  - OBJECTIVE: To investigate changes in the range of suicide methods used in two
      time periods a century apart (1901-1907 and 2001-2007) in England and Wales.
      METHOD: Suicide mortality and population data were obtained for England and Wales
      from the ONS and used to calculate gender and method-specific mortality rates.
      RESULTS: There have been striking changes in the methods of suicide used since
      the 1900s. Hanging was the most commonly used method during both time periods.
      However suicides involving drowning (22.5% of suicides in 1901-1907) and weapons
      (e.g. firearms and razors, 24.2% of suicides in 1901-1907) were rarely used in
      2001-2007 (2.6% and 5.8% respectively). Although the use of poisons was popular
      in both time periods, the types of poisons used differed substantially over time.
      Household cleaning products and disinfectants accounted for almost half of
      poisoning suicides in the early 1900s whereas self-poisoning with medicines
      accounted for most poisoning suicides in 2001-2007. LIMITATIONS: There were
      changes in the coding of suicides over time. Additionally, deaths by drowning and
      poisoning are more difficult to confirm as suicides than those that occur due to
      hanging or the use of weapons. CONCLUSIONS: The changes in popularity of some
      suicide methods can be mainly attributed to changes in the physical availability
      (access) of these methods over time. Other methods which remain readily available
      have fallen out of fashion in recent times, suggesting a contributory role of
      other factors such as cognitive availability and personal
      preference/acceptability in influencing the choice of suicide method.

PMID- 22871524
TI  - Presynaptic GABA(B) receptors decrease neurotransmitter release in vestibular
      nuclei neurons during vestibular compensation.
AB  - Unilateral damage to the peripheral vestibular receptors precipitates a
      debilitating syndrome of oculomotor and balance deficits at rest, which
      extensively normalize during the first week after the lesion due to vestibular
      compensation. In vivo studies suggest that GABA(B) receptor activation
      facilitates recovery. However, the presynaptic or postsynaptic sites of action of
      GABA(B) receptors in vestibular nuclei neurons after lesions have not been
      determined. Accordingly, here presynaptic and postsynaptic GABA(B) receptor
      activity in principal cells of the tangential nucleus, a major avian vestibular
      nucleus, was investigated using patch-clamp recordings correlated with
      immunolabeling and confocal imaging of the GABA(B) receptor subunit-2 (GABA(B)R2)
      in controls and operated chickens shortly after unilateral vestibular
      ganglionectomy (UVG). Baclofen, a GABA(B) agonist, generated no postsynaptic
      currents in principal cells in controls, which correlated with weak GABA(B)R2
      immunolabeling on principal cell surfaces. However, baclofen decreased miniature
      excitatory postsynaptic current (mEPSC) and GABAergic miniature inhibitory
      postsynaptic current (mIPSC) events in principal cells in controls, compensating
      and uncompensated chickens three days after UVG, indicating the presence of
      functional GABA(B) receptors on presynaptic terminals. Baclofen decreased
      GABAergic mIPSC frequency to the greatest extent in principal cells on the intact
      side of compensating chickens, with concurrent increases in GABA(B)R2 pixel
      brightness and percentage overlap in synaptotagmin 2-labeled terminals. In
      uncompensated chickens, baclofen decreased mEPSC frequency to the greatest extent
      in principal cells on the intact side, with concurrent increases in GABA(B)R2
      pixel brightness and percentage overlap in synaptotagmin 1-labeled terminals.
      Altogether, these results revealed changes in presynaptic GABA(B) receptor
      function and expression which differed in compensating and uncompensated chickens
      shortly after UVG. This work supports an important role for GABA(B) autoreceptor
      mediated inhibition in vestibular nuclei neurons on the intact side during early
      stages of vestibular compensation, and a role for GABA(B) heteroreceptor-mediated
      inhibition of glutamatergic terminals on the intact side in the failure to
      recover function.

PMID- 22871527
TI  - Gender ratio comparisons of the suicide rates and methods in Korea, Japan,
      Australia, and the United States.
AB  - BACKGROUND: The gender ratio (male/female) of suicide rates greatly differs by
      country and by age group. These differences are accompanied by differences in the
      use of violent methods of suicide. METHODS: The gender ratio of suicide rates and
      the methods used were calculated from the most recently available official
      electronic mortality data published by the four countries (two Eastern (Korea and
      Japan) and two Western (Australia and the United states) countries) and from the
      World Health Organization [WHO] mortality database. Suicide gender ratios based
      on 95% Confidence intervals (CIs) were used to compare the countries between age
      groups. RESULTS: The gender ratio of suicide rates was higher in the United
      States (3.9) and Australia (3.3), where gender differences in suicide methods
      were more prominent, than in Korea (1.8) and Japan (2.7). In the United States
      and Australia, the gender ratios greatly increased in the elderly (age 70 years
      and over), with a higher use of firearms by men. The gender ratio of suicide
      rates was lowest (1.0) in the young (age 20-29) in Korea, where hanging was a
      more common method in women than in men. LIMITATIONS: The study does not consider
      the various other factors that may have influenced gender differences of suicide
      rate. CONCLUSIONS: These findings suggest that differences in suicide methods
      play a role in determining the differences in the gender ratio of suicide rates
      between countries. Because suicide methods varied with gender, age, and country
      and may play a role in the suicide rates of each group, these parameters should
      be taken into account in the design of suicide prevention measures.

PMID- 22871528
TI  - The relationship between social integration and depression in non-demented
      primary care patients aged 75 years and older.
AB  - BACKGROUND: Social integration seems to be associated with depression in late
      life. But the measurement of social integration still lacks a strong consensus.
      To date in most studies the different domains of social integration have been
      examined separately. AIMS: In order to improve comparability among studies, we
      used the social integration index (SII), which covers all domains of social
      integration, to examine the association of social integration and depression in
      non-demented primary care patients aged 75 years and older. METHOD: Data were
      derived from the longitudinal German study on Aging, Cognition and Dementia in
      primary care patients. Included in the cross-sectional survey were 1028 non
      demented subjects aged 75 years and older. The GDS-15 Geriatric Depression Scale
      was used to measure depression with a threshold of >=6. Associations of the SII
      and further potential risk factors and depression were analysed using
      multivariate logistic regression models. RESULTS: The SII was significantly
      associated with depression in the elderly. After full adjustment for all
      variables, odds of depression were significantly higher for lower levels of the
      SII, having a care level, impaired vision and mobility and subjective memory
      complaints. CONCLUSION: Because the social integration index covers several
      aspects of social integration, the results seem to be more significant than
      considering only one of these domains alone. Further research is needed to prove
      the practicability of the social integration index and to supply the literature
      with consistent results regarding the association of social integration and
      depression. Elderly with depression could benefit from increased social networks
      and enhanced social integration, which points to the development of social
      programs and social policies that maximize the engagement of older adults in
      social activities and volunteer roles.

PMID- 22871529
TI  - Prolonged grief disorder three decades post loss in survivors of the Khmer Rouge
      regime in Cambodia.
AB  - BACKGROUND: During the Khmer Rouge (KR) regime from 1975 to 1979 millions of
      Cambodians were confronted with the death or murder of family members. The long
      term psychological consequences of these traumatic losses have not yet been
      investigated. The purpose of this study was to determine the rate and potential
      predictors of prolonged grief disorder (PGD) in survivors of the KR regime.
      METHOD: The Inventory of Complicated Grief-Revised (ICG-R) was administered in a
      sample of N=775 Cambodians in face-to-face interviews who had lost at least one
      family member during the KR regime. Symptoms of PTSD were assessed with the PTSD
      Checklist-Civilian Version and symptoms of depression and anxiety with the
      Hopkins Symptom Checklist-25. RESULTS: The prevalence of PGD in the sample was
      14.3%. PGD was moderately associated with symptoms of depression, anxiety and
      PTSD. The loss of a spouse, a child, or a parent was associated with higher
      symptom severity of PGD than was the loss of a sibling or distant relatives. PGD
      was predicted by the relationship to the deceased and symptoms of depression and
      PTSD. LIMITATIONS: Limitations of the study include the non-random sampling
      recruitment. The ICG-R has not been validated for use in Cambodia. CONCLUSIONS:
      The vast majority of Cambodians lost family members during the KR regime. Even
      three decades later, PGD was prevalent in a substantial proportion of the present
      sample and related to other psychiatric disorders. The results underline the
      importance of examining PGD in studies of war-related psychological impairment.

PMID- 22871530
TI  - Aggression and impulsivity as predictors of stress generation in bipolar spectrum
      disorders.
AB  - BACKGROUND: Some evidence suggests that individuals with bipolar spectrum
      disorders (BSD) generate stressful life events, contributing to a more severe
      course of disorder. A recent update to the Behavioral Approach System (BAS)
      dysregulation theory of BSD highlights the need to investigate anger as approach
      motivation. Although research has shown that individuals with BSD generate
      stress, it is unclear whether personality traits characteristic of BSD, such as
      aggression and impulsivity, are related to this stress generation. METHODS: The
      current longitudinal study employed multilevel modeling to examine stress
      generation in a sample of 104 individuals with BSD and 96 healthy controls. We
      examined rates of BAS-deactivating, BAS-activating, and Anger-evoking life events
      over a period of up to 4.5 years as a function of levels of aggression and
      impulsivity. RESULTS: Individuals with BSD reported significantly higher numbers
      of dependent Anger-evoking events and BAS-deactivating events, but not dependent
      BAS-activating events, than controls. Trait levels of hostility and impulsivity
      predicted all types of events, although bipolar diagnosis remained a significant
      predictor of BAS-deactivating and Anger-evoking events. LIMITATIONS: The life
      events measures were not designed to assess Anger-evoking events; further
      research should replicate these findings and develop more finely tuned
      assessments of stressful anger events. In addition, the sample was not a clinical
      sample. CONCLUSIONS: This study adds to the literature on stress generation in
      BSD; trait level personality differences predict stress generation, beyond
      bipolar diagnosis. This also further establishes the importance of including
      anger-evoking events in the BAS model of BSDs and stress generation.

PMID- 22871532
TI  - The reliability and validity of the Everyday Feelings Questionnaire in a clinical
      population.
AB  - BACKGROUND: Depression could be considered to be on a continuum with well-being
      and some have argued that it is important to measure well-being as well as
      distress. The Everyday Feelings Questionnaire was designed to measure both these
      aspects. Its validity has been assessed in a nonclinical population. This project
      aims to assess the validity and reliability of the EFQ in a clinical population.
      METHODS: The EFQ was completed by 105 clients within a mental health clinical
      setting. The following aspects of the EFQ were explored: its internal structure,
      concurrent validity, re-test reliability and internal consistency. RESULTS: The
      EFQ had good internal consistency and correlated highly with other measures of
      anxiety and depression. The correlation between total EFQ scores on the two
      occasions was reasonable and there was no effect of time during completion. A
      Bland-Altman plot showed no obvious pattern between the difference between EFQ
      scores and the mean score. A one factor model showed a moderate fit to the data.
      LIMITATIONS: This study does not explore the acceptability or sensitivity to
      change of the EFQ, and a larger sample size would be needed to extend the
      analysis conducted. CONCLUSIONS: The EFQ is a valid and reliable measure when
      used in this clinical population.

PMID- 22871531
TI  - Baseline delta sleep ratio predicts acute ketamine mood response in major
      depressive disorder.
AB  - BACKGROUND: Electroencephalographic (EEG) sleep slow wave activity (SWA; EEG
      power between 0.6 and 4Hz) has been proposed as a marker of central synaptic
      plasticity. Decreased generation of sleep slow waves--a core feature of sleep in
      depression--indicates underlying plasticity changes in the disease. Various
      measures of SWA have previously been used to predict antidepressant treatment
      response. This study examined the relationship between baseline patterns of SWA
      in the first two NREM episodes and antidepressant response to an acute infusion
      of the N-methyl-d-aspartate (NMDA) antagonist ketamine. METHODS: Thirty patients
      (20M, 10F, 18-65) fulfilling DSM-IV criteria for treatment-resistant major
      depressive disorder (MDD) who had been drug-free for two weeks received a single
      open-label infusion of ketamine hydrochloride (.5mg/kg) over 40 min. Depressive
      symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS)
      before and after ketamine infusion. Sleep recordings were obtained the night
      before the infusion and were visually scored. SWA was computed for individual
      artifact-free NREM sleep epochs, and averaged for each NREM episode. Delta sleep
      ratio (DSR) was calculated as SWA(NREM1)/SWA(NREM2). RESULTS: A significant
      positive correlation was observed between baseline DSR and reduced MADRS scores
      from baseline to Day 1 (r=.414, p=.02). LIMITATIONS: The sample size was
      relatively small (N=30) and all subjects had treatment-resistant MDD, which may
      limit the generalizability of the findings. Further studies are needed to
      replicate and extend this observation to other patient groups. CONCLUSIONS: DSR
      may be a useful baseline predictor of ketamine response in individuals with
      treatment-resistant MDD.

PMID- 22871533
TI  - Suicide in recently admitted psychiatric in-patients: a case-control study.
AB  - BACKGROUND: Around a quarter of in-patient suicides occur within the first week
      of admission to psychiatric in-patient care. Little is known on the factors
      associated with suicide during this critical time. We aimed to identify risk
      factors for suicide among in-patients within the first week of admission.
      METHODS: A national population-based case-control study of 107 current
      psychiatric in-patients in England who died by suicide within a week of
      admission, matched on admission date with 107 living controls. RESULTS: Forty-two
      (40%) suicide cases died within the first 3 day of admission. A fifth of all
      suicides were on authorised leave at the time of death, but 34% were off the ward
      without staff agreement compared to only 1% of controls. Independent risk factors
      for suicide included previous self-harm, recent adverse life events, and a short
      (<12 months) duration of illness. LIMITATIONS: This is a retrospective study,
      using clinical data mainly collected from case records. Clinicians were not blind
      to case/control status. CONCLUSIONS: The first few days of admission should be
      recognised as the period of highest risk. Careful risk evaluation is needed at
      this time, particularly in those with recent illness onset or previous suicide
      attempts. Knowledge of life events experienced before admission should be
      incorporated into risk assessments. Improvements to the ward environment to
      lessen the distress of an admission may be an important preventative measure.
      Protocols may require adapting to improve the safety of those on agreed leave,
      and prevent absconding through increased vigilance and closer observation of ward
      exits.

PMID- 22871535
TI  - Obesity and suicide risk in adults--a systematic review.
AB  - BACKGROUND: There is evidence from prospective studies that obesity is positively
      associated with depression. In contradiction to this, however, a number of
      studies have revealed that the number of completed suicides decreases with
      increasing BMI. The objective of this systematic review is to elucidate this
      ambiguous research field, providing an overview of literature examining the
      relationship between obesity and risk of suicide in adults (>18 years). METHODS:
      Literature searches of the databases PubMed/Medline, PsychInfo, and Web of
      Sciences were conducted. Fifteen studies concerning completed suicide, suicide
      attempts and suicidal ideation met the inclusion criteria (seven prospective and
      eight cross-sectional studies). RESULTS: Eight studies evaluating completed
      suicide reported an inverse relationship between BMI and suicide, meaning that
      obese people are less likely to commit suicide than people of low or normal
      weight, whereas one study showed no association and one showed a positive
      association. Studies about suicide attempts and ideation, on the other hand,
      found results that differed depending on gender. While obese woman reported more
      suicide attempts and suicidal ideation, obese men reported less attempts and
      thoughts. DISCUSSION: The role of confounding variables such as age or
      psychiatric illness on suicide risk are discussed and remaining research
      questions are outlined, especially regarding the role of different underlying
      biological pathways and consideration of different classes of obesity.

PMID- 22871534
TI  - Suicide attempts in veterans with bipolar disorder during treatment with lithium,
      divalproex, and atypical antipsychotics.
AB  - Suicide attempt rates were assessed in 1306 subjects in this 6 year retrospective
      study of Bipolar disorder. Participants were Veterans from 5 different Veterans
      Administration Hospitals who met criteria for bipolar type 1 or 2 and who had at
      least one prescription for lithium or divalproex or both during the study period.
      This study focused on the impact of atypical antipsychotics on the suicide
      attempt rate when used in addition to or in place of lithium or divalproex.
      Medication exposure was calculated using computerized pharmacy records. Suicide
      attempts were established through chart review including emergency room records,
      inpatient records, and outpatient records. There were a total of 117 suicide
      attempts and 2 suicide completions during the study period. Most attempts (59%)
      occurred when patients were on no medications. Nearly 90% of subjects spent an
      average of 45 months during the 6 year period on none of the aforementioned
      medications. The lowest percentage of suicide attempts (15%) occurred while on
      lithium, 21% while on divalproex and 24% while on atypical antipsychotics. When
      total months of exposure were taken into account, the lowest attempt rate
      occurred on lithium plus divalproex (6.3 attempts per 10,000 months of exposure),
      followed by divalproex alone (7.0 attempts/10,000 months of exposure), and
      lithium alone (7.7 attempts per 10,000 months of exposure). Patients on atypical
      antipsychotics alone had an attempt rate of 26.1 attempts per 10,000 months of
      exposure. In this study, lithium and divalproex provided protection against
      suicide attempts. Results need to be replicated in future prospective studies and
      clearly strategies for improving medication compliance among veterans are
      warranted.

PMID- 22871536
TI  - Diagnostic conversions from major depressive disorder into bipolar disorder in an
      outpatient setting: results of a retrospective chart review.
AB  - BACKGROUND: The aim of the study was to check the stability of a diagnosis of
      major depressive disorder (MDD) in an outpatient setting, as well as to assess
      the scope of diagnostic conversions into bipolar disorder (BD). METHODS:
      Retrospective chart review of 122 patients with a primary diagnosis of MDD.
      RESULTS: Diagnostic conversion from MDD into BD was noticed in 40 subjects
      (32.8%), 25 patients (20.5%) were treatment-resistant. Mean time to the
      conversion was 9.27+/-8.64 years. A negative correlation between the age of
      illness onset and time to diagnostic conversion was observed (-0.41; p<0.05).
      Earlier onset of MDD was associated with higher risk of diagnostic conversion
      (<30vs>=30 years of age at onset: 69% vs 28%, p=0.0001; <35vs>=35 years of age:
      50% vs 25%, p=0.0065). Treatment-resistance was more prevalent in the BD
      conversion group (40% vs 11%; p=0.0002). Diagnostic conversion into BD was also
      related longer duration of treatment received, higher number of illness episodes,
      and higher number of hospitalizations. LIMITATIONS: Retrospective design of the
      study. CONCLUSIONS: The problem of diagnosis evolution from MDD to BD was
      observed in about 1/3 of patients, and was associated with treatment-resistance
      of depression, earlier onset of depression, longer time of treatment, higher
      number of depressive episodes and hospitalizations. The variables above may be a
      useful predictor of bipolar diathesis.

PMID- 22871537
TI  - Do patients with advanced cognitive impairment admitted to hospitals with higher
      rates of feeding tube insertion have improved survival?
AB  - CONTEXT: Research is conflicting on whether receiving medical care at a hospital
      with more aggressive treatment patterns improves survival. OBJECTIVES: The aim of
      this study was to examine whether nursing home residents admitted to hospitals
      with more aggressive patterns of feeding tube insertion had improved survival.
      METHODS: Using the 1999-2007 Minimum Data Set matched to Medicare claims, we
      identified hospitalized nursing home residents with advanced cognitive impairment
      who did not have a feeding tube inserted prior to their hospital admissions. The
      sample included 56,824 nursing home residents and 1773 acute care hospitals
      nationwide. Hospitals were categorized into nine groups based on feeding tube
      insertion rates and whether the rates were increasing, staying the same, or
      decreasing between the periods of 2000-2003 and 2004-2007. Multivariate logit
      models were used to examine the association between the hospital patterns of
      feeding tube insertion and survival among hospitalized nursing home residents
      with advanced cognitive impairment. RESULTS: Nearly one in five hospitals (N=366)
      had persistently high rates of feeding tube insertion. Being admitted to these
      hospitals with persistently high rates of feeding tube insertion was not
      associated with improved survival when compared with being admitted to hospitals
      with persistently low rates of feeding tube insertion. The adjusted odds ratios
      were 0.93 (95% confidence interval [CI]: 0.87, 1.01) and 1.02 (95% CI: 0.95,
      1.09) for one-month and six-month posthospitalization survival, respectively.
      CONCLUSION: Hospitals with more aggressive patterns of feeding tube insertion did
      not have improved survival for hospitalized nursing home residents with advanced
      cognitive impairment.

PMID- 22871538
TI  - Voluntary wheel running attenuates ethanol withdrawal-induced increases in
      seizure susceptibility in male and female rats.
AB  - We recently found that voluntary wheel running attenuated ethanol withdrawal
      induced increased susceptibility to chemoconvulsant-induced seizures in male
      rats. Since female rats recover from ethanol withdrawal (EW) more quickly than
      male rats across several behavioral measures, this study was designed to
      determine whether the effects of exercise on EW seizures also exhibited sex
      differences. Animals were maintained under no-wheel, locked-wheel or free-wheel
      conditions and ethanol was administered by liquid diet for 14 days with control
      animals pair-fed an isocaloric diet, after which seizure thresholds were
      determined at 1 day or 3 days of EW. Consistent with previous reports, females
      ran significantly more than males, regardless of diet condition. Introduction of
      the ethanol-containing liquid diet dramatically increased running for females
      during the day (rest) phase, with little impact on night phase activity.
      Consistent with previous reports, EW increased seizure susceptibility at 1 day in
      non-exercising males and females and at 3 days in males. These effects were
      attenuated by access to running wheels in both sexes. We also assessed the
      effects of sex, ethanol diet and exercise on ethanol clearance following an acute
      ethanol administration at 1 day EW in a separate set of animals. Blood ethanol
      concentrations at 30 min post-injection were lower in males, ethanol-exposed
      animals, and runners, but no interactions among these factors were detected.
      Interestingly, females displayed more rapid ethanol clearance than males and
      there were no effects of either diet or wheel access on clearance rates. Taken
      together, these data suggest that voluntary wheel running during ethanol
      administration provides protective effects against EW seizures in both males and
      females. This effect may be mediated, in part, in male, but not in female rat, by
      effects of exercise on early pharmacokinetic contributions. This supports the
      idea that encouraging alcoholics to exercise may benefit their recovery.

PMID- 22871539
TI  - Fat necrosis may mimic local recurrence of breast cancer in FDG PET/CT.
AB  - Fat necrosis of the breast is a benign condition that most commonly occurs as the
      result of trauma. The radiographic and clinical significance of fat necrosis of
      the breast is that it may mimic malignancy. We present a case of false positive
      FDG PET/CT scan caused by fat necrosis and mimics local recurrence of breast
      carcinoma 3 years after radical mastectomy. Physicians must be aware of fat
      necrosis as a potential pitfall for PET/CT. Fat necrosis must be considered in
      the differential diagnosis of hypermetabolic breast masses in patients who
      previously had mastectomy or mammoplasty.

PMID- 22871540
TI  - Sequence analysis, expression patterns and transcriptional regulation of mouse
      Ifrg15 during preimplantation embryonic development.
AB  - Ifrg15 is a newly identified interferon alpha responsive gene and is implicated
      in a wide variety of physiological roles in mammals. In the present study,
      multiple alignments of the deduced amino acids of 10 eutherian mammalian
      IFRG15/Ifrg15s isolated from open genomic database revealed that they were highly
      conserved. Real-time PCR showed that mouse Ifrg15 mRNA was expressed in MII stage
      oocytes and preimplantation embryos, and its highest value peaked at the stage of
      mouse blastocysts. To understand the effect of three development-related genes on
      the promoter activity of mouse Ifrg15, promoter analysis using luciferase assays
      in COS-7 cells were performed. The results showed that the transcription of mouse
      Ifrg15 was suppressed by Oct4 and Nanog when transfected with the longest Ifrg15
      promoter reporter gene. After the relatively shorter promoters were co
      transfected with Oct4, c-Myc and Nanog, the relative luciferase activities of
      Ifrg15 were gradually increased. These in vitro results data and expression
      profiles of Ifrg15 as revealed by real-time PCR partly indicated that Ifrg15
      transcription might be either potentially regulated or dependent on the post
      transcriptional effects of IFN-alpha mediated by the three genes indirectly. Our
      data suggested that the mouse Ifrg15 might interact with these key development
      related genes and play significant roles on the mouse preimplantation embryos
      development, especially for the development of mouse blastocysts.

PMID- 22871541
TI  - Cognitive dysfunction profile and arterial stiffness in type 2 diabetes.
AB  - BACKGROUND: The causative mechanisms of type 2 diabetes (T2D) on cognitive
      dysfunction are still undergoing development. AIM: To explore the cognitive
      dysfunction profile and its relation to the potential role of arterial stiffness
      in later middle age T2D patients. METHODS: We studied 37 patients with T2D (age
      range 45-65 years) and 22 normal controls. All participants underwent
      comprehensive neuropsychological assessment. The carotid-femoral pulse wave
      velocity (CF-PWV) measurements were taken with the PulsePen device. RESULTS: Our
      results showed significantly poorer performance on all tests assessing
      attention/executive functions and processing speed in patients with T2D. In
      addition to cognitive slowing T2D patients demonstrated significant deficits in
      almost all measures of verbal episodic memory after adjustment for age, education
      and blood pressure (BP) levels (p<0.05). Carotid-femoral pulse wave velocity (CF
      PWV) appeared significantly higher in T2D subjects than in normal controls after
      adjustment for age and BP level (p<0.001). Significant relationship was observed
      between CF-PWV and cognitive status. CONCLUSION: We revealed that arterial
      stiffness was increased and associated with cognitive impairment in T2D. The
      cognitive profile indicates hippocampal amnestic type mild cognitive impairment
      associated with a pronounced dysexecutive syndrome suggesting that diabetes may
      affect cognition through both vascular and neurodegenerative processes. However,
      neurodegenerative cognitive profile caused by hippocampal atrophy in a pure
      vascular process could not be excluded.

PMID- 22871542
TI  - Vascular lesions in mixed dementia, vascular dementia, and Alzheimer disease with
      cerebrovascular disease: the Kurihara Project.
AB  - The concept and diagnosis for mixed dementia is not simple, since it is difficult
      to identify the type and regions of cerebrovascular disease (CVD) responsible for
      causing dementia. An investigation is needed to confirm the presence of mixed
      dementia, those who met the criteria for Alzheimer's disease (AD) and those for
      vascular dementia (VaD). According to the community-based stroke, dementia, and
      bed-confinement prevention in Kurihara, northern Japan (Kurihara Project), the
      prevalence of dementia and dementing diseases was surveyed in 2008-2010. Five
      hundred and ninety people finally agreed to participate (47.0%), and 73 (12.4%)
      people were diagnosed with dementia according to the DSM-IV. Using MRI, intensive
      evaluations on CVDs were performed for the 49 dementia patients associated with
      CVDs (mixed dementia, VaD, and AD with CVD). For the mixed dementia group, all
      had left subcortical strategic CVDs. These included the caudate head and
      thalamus. For the VaD group, all patients had at least cortical CVDs or
      subcortical strategic CVDs. The AD with CVD group had non-strategic CVDs in
      cortical, subcortical, or other areas in 5 or 6 patients each. Two extreme
      concepts regarding CVD and dementia are possible. One is that there is no concept
      for mixed dementia or VaD. An alternative is that the vascular factor should be
      considered as primary. Our data showed an importance of cortical and subcortical
      "strategic" areas, the latter included thalamus and caudate head.

PMID- 22871544
TI  - Acute first onset of Ehlers-Danlos syndrome type 4 with spontaneous rupture of
      posterior tibial artery pseudoaneurysm.
AB  - Ehlers-Danlos syndrome type 4, the vascular type, is a rare, life-threatening
      inherited disorder of the connective tissue. Affected patients are at risk of
      arterial, bowel and uterine rupture during pregnancy. Generally, this syndrome
      remains undiagnosed until a sudden, acute presentation with organ rupture, and
      results in premature death, even if the patients survive the first and second
      major complications. An early diagnosis with genetic assays can help to plan the
      best treatment, which is often challenging due to the frailty of the arterial
      tissue. We report on a 28-year-old lady who presented with spontaneous rupture of
      a pseudoaneurysm of the posterior tibial artery.

PMID- 22871545
TI  - Primary aortoenteric fistula following disseminated bacillus Calmette-Guerin
      infection: a case report.
AB  - The aim of this paper is to illustrate a rare case of primary aortoenteric
      fistula in the presence of disseminated infection and review the critical
      decision-making process. A clinical case was reviewed for its initial
      presentation, planning of treatment strategy and outcome. A secondary literature
      search for discussion on current accepted recommendations for primary
      aortoenteric fistula was then completed. Aortoenteric fistulas are rare
      pathologies with highly morbid potential. Their diagnosis requires a high index
      of suspicion and prompt intervention is critical to patient survival. In
      conclusion, aortoenteric fistula most commonly arises from large atherosclerotic
      aneurysms but can be caused by systemic infection. In the case of the latter,
      extra-anatomic repair appears to be the treatment of choice.

PMID- 22871546
TI  - Popliteal artery entrapment syndrome: report of two cases.
AB  - Popliteal artery entrapment syndrome accounts for an important part of
      correctible causes of claudication and limb ischemia in young people. It is
      caused by an abnormal relation between the popliteal artery (PA) and the medial
      head of the gastrocnemius muscle. The diagnosis should be considered in any
      patient under 50 with calf claudication. The mainstay of treatment is prevention
      of PA fibrosis because if left untreated, the syndrome leads to irreversible
      damage to the PA with thrombosis and limb ischemia. We describe two cases of
      different types in 21- and 27-year-old males, respectively, and we review the
      literature about the presentation, diagnosis, classification and management of
      this entity.

PMID- 22871547
TI  - Attending to the construct of beliefs in research on religion/spirituality and
      health: commentary on 'beyond belief'.
AB  - In this commentary, I concur with Cromby that more attention should be given to
      beliefs in terms of definition, measurement, and investigation, particularly of
      their development and their relations with aspects of health and well-being.
      Within the context of religious beliefs, I argue, however, that beliefs should
      not be considered affect or emotion but rather should be examined in relation to
      them, and that their development likely arises through myriad sources. I provide
      an alternative definition of religious beliefs and conclude with suggestions for
      future research on religious beliefs and health.

PMID- 22871543
TI  - Critical pathogenic events underlying progression of neurodegeneration in
      glaucoma.
AB  - Glaucoma is a common optic neuropathy with a complex etiology often linked to
      sensitivity to intraocular pressure. Though the precise mechanisms that mediate
      or transduce this sensitivity are not clear, the axon of the retinal ganglion
      cell appears to be vulnerable to disease-relevant stressors early in progression.
      One reason may be because the axon is generally thin for both its unmyelinated
      and myelinated segment and much longer than the thicker unmyelinated axons of
      other excitatory retinal neurons. This difference may predispose the axon to
      metabolic and oxidative injury, especially at distal sites where pre-synaptic
      terminals form connections in the brain. This idea is consistent with
      observations of early loss of anterograde transport at central targets and other
      signs of distal axonopathy that accompany physiological indicators of
      progression. Outright degeneration of the optic projection ensues after a
      critical period and, at least in animal models, is highly sensitive to cumulative
      exposure to elevated pressure in the eye. Stress emanating from the optic nerve
      head can induce not only distal axonopathy with aspects of dying back neuropathy,
      but also Wallerian degeneration of the optic nerve and tract and a proximal
      program involving synaptic and dendritic pruning in the retina. Balance between
      progressive and acute mechanisms likely varies with the level of stress placed on
      the unmyelinated axon as it traverses the nerve head, with more acute insult
      pushing the system toward quicker disassembly. A constellation of signaling
      factors likely contribute to the transduction of stress to the axon, so that
      degenerative events along the length of the optic projection progress in
      retinotopic fashion. This pattern leads to well-defined sectors of functional
      depletion, even at distal-most sites in the pathway. While ganglion cell somatic
      drop-out is later in progression, some evidence suggests that synaptic and
      dendritic pruning in the retina may be a more dynamic process. Structural
      persistence both in the retina and in central projection sites offers the
      possibility that intrinsic self-repair pathways counter pathogenic mechanisms to
      delay as long as possible outright loss of tissue.

PMID- 22871548
TI  - A comparative experimental and quantum chemical study on monomeric and dimeric
      structures of 3,5-dibromoanthranilic acid.
AB  - This study presents the structural and spectroscopic characterization of 3,5
      dibromoanthranilic acid with help of experimental techniques (FT-IR, FT-Raman,
      UV, NMR) and quantum chemical calculations. The vibrational spectra of title
      compound were recorded in solid state with FT-IR and FT-Raman in the range of
      4000-400 and 4000-50 cm(-1), respectively. The vibrational frequencies were also
      computed using B3LYP method of DFT with 6-311++G(d,p) basis set. The fundamental
      assignments were done on the basis of the total energy distribution (TED) of the
      vibrational modes, calculated with scaled quantum mechanical (SQM) method. The
      (1)H, (13)C and DEPT NMR spectra were recorded in DMSO solution and calculated by
      gauge-invariant atomic orbitals (GIAO) method. The UV absorption spectra of the
      compound were recorded in the range of 200-400 nm in ethanol, water and DMSO
      solutions. Solvent effects were calculated using time-dependent density
      functional theory and CIS method. The ground state geometrical structure of
      compound was predicted by B3LYP method and compared with the crystallographic
      structure of similar compounds. All calculations were made for monomeric and
      dimeric structure of compound. Moreover, molecular electrostatic potential (MEP)
      and thermodynamic properties were performed. Mulliken atomic charges of neutral
      and anionic form of the molecule were computed and compared with anthranilic
      acid.

PMID- 22871549
TI  - Synthesis, X-ray structural, characterization, NBO and HOMO-LUMO analysis using
      DFT study of 4-methyl-N-(naphthalene-1-yl)benzene sulfonamide.
AB  - The sulfonamide compound, 4-methyl-N-(naphthalene-1-yl)benzene sulfonamide
      (abbreviated as 4MNBS) was synthesized from the reaction of 4-methyl benzene
      sulfonyl chloride with 1-naphthyl amine. The 4MNBS was characterized by FTIR,
      (1)H NMR, (13)C NMR, single crystal X-ray diffraction (XRD) and thermal analysis.
      By using the Density Functional Theory (DFT) method with 6-31G(d,p) basis set,
      the molecular geometry and vibrational frequencies were calculated and compared
      with the experimental data. The title compound crystallizes in the triclinic
      system of space group p-1 with a=10.3873(7)A, b=10.4090(7)A, c=15.7084(10)A;
      alpha=75.735(3) degrees ; beta=70.737(3) degrees ; gamma=68.120(3) degrees  and
      z=4. Stability of the molecule arising from hyper conjugative interactions,
      charge delocalization has been analyzed using natural bond orbital (NBO)
      analysis. In addition, atomic charges, frontier molecular orbitals and molecular
      electrostatic potential were computed by using Density Functional Theory
      (DFT/B3LYP) 6-31G(d,p) basis set. The calculated HOMO and LUMO energies show that
      charge transfer occurs in the molecule.

PMID- 22871551
TI  - Silibinin modulates the NF-kappab pathway and pro-inflammatory cytokine
      production by mononuclear cells from preeclamptic women.
AB  - Preeclampsia (PE) is a complication of human pregnancy associated with an intense
      inflammatory response involving leukocyte activation, as well as elevated
      production of pro-inflammatory cytokines. The nuclear transcription factor-kappa
      B (NF-kappaB) is present in cells of the immune system and is responsible for
      transcription of genes coding for pro-inflammatory proteins. Silibinin is the
      main component of silymarin, a polyphenolic extract obtained from fruits and
      seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory
      activities. In this study, we assessed whether silibinin modulated NF-kappaB
      activity and the production of pro-inflammatory cytokines by peripheral blood
      mononuclear cells (PBMCs) from preeclamptic patients. PBMC from women with PE,
      normotensive (NT) pregnant women, and nonpregnant (NP) women were cultured with
      or without silibinin (5 MUM and 50 MUM) and 1 MUg/mL lipopolysaccharide (LPS) for
      18 h. The supernatants were assayed for tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1 beta (IL-1beta) by ELISA. Cells were cultured for 30 min to
      evaluate NF-kappaB activity. There was increased endogenous activation of NF
      kappaB as well as TNF-alpha and IL-1beta release by PBMC in the PE group compared
      with the NT and NP groups. A positive correlation between NF-kappaB activity and
      cytokine production was also observed in the PE group. Silibinin was capable of
      reducing, at least in part, the levels of NF-kappaB and cytokines TNF-alpha and
      IL-1beta in preeclamptic women. We conclude that silibinin exhibits potent anti
      inflammatory activity on PBMC from preeclamptic women by downmodulation of NF
      kappaB activation and inflammatory cytokine production.

PMID- 22871552
TI  - Severity of symptoms of depression among burned patients one week after injury,
      using Beck Depression Inventory-II (BDI-II).
AB  - BACKGROUND: This study was done to determine the severity of symptoms of
      depression in burned patients and to assess the effect of burn related factors on
      depression. MATERIALS AND METHODS: This is a descriptive cross-sectional survey,
      performed in Burn center, Motahhari hospital, Tehran University of Medical
      Sciences, Iran. The population of the study included 300 hospitalized patients
      from April 2010 to May 2011 who were assessed for symptoms of depression one week
      after burn injury by Beck Depression Inventory-II. RESULTS: Three hundred
      subjects (50% female and 50% male) participated in the study. Age ranged from 13
      to 75 with the mean of 35.06+/-12.79 years. 184 (61.3%) had symptoms of
      depression, 58 (19.3%) of them mild, 52 (17.3%) moderate and 74 (24.7%) severe
      depression symptoms. There was a significant relationship between symptoms of
      depression and age, gender, educational level, TBSA%, number of burn sites and
      amputation (p value<0.05). CONCLUSION: The high prevalence of symptoms of
      depression in burned patients suggests that depression should be screened in such
      patients and treat if indicated.

PMID- 22871550
TI  - Structural basis for protein synthesis: snapshots of the ribosome in motion.
AB  - The ribosome undergoes numerous large-scale conformational changes during protein
      synthesis, but the molecular basis for these changes have been unclear. Recent
      cryo-electron microscopic and X-ray crystallographic structures of both the
      bacterial and eukaryotic ribosome now provide snapshots of the wide range of
      motions that occur within the ribosome. X-ray crystallographic structures of the
      ribosome have also pinpointed local deformations in ribosomal RNA that occur when
      the two ribosomal subunits rotate with respect to each other. These structural
      results establish the foundation for unraveling the mechanics of the ribosome
      that are universal, and those that differ in bacteria and eukaryotes.

PMID- 22871553
TI  - A novel axillary dressing to minimize shearing forces post skin grafting in burns
      patients.

PMID- 22871554
TI  - Colistin in burn intensive care: back to the future?
AB  - Colistin is a venerable antibiotic whose fortunes have been revived by its
      excellent activity, the diminishing output of novel clinically effective
      antibiotics and the increasing importance of MDR infection in burn surgery, both
      in the civilian and military arenas. This review synthesizes current evidence on
      the usage of colistin in burn surgery including the structure-activity
      relationship; dosing, pharmacokinetics/pharmacodynamic (PK/PD), analytic methods,
      resistance and current research efforts into the redevelopment of this
      antibiotic, to distil recommendations for future research and clinical efficacy.

PMID- 22871555
TI  - Microbiology of wildfire victims differs significantly from routine burns
      patients: data from an Australian wildfire disaster.
AB  - The catastrophic wildfires of February 2009 in Victoria, Australia killed 173
      people and hospitalised 18 adults with burns. We conducted a case-control study
      of wildfire victims (WFVs) compared to routine burns patients to assess early
      differences in bacteriology. Demographic, outcome and bacteriology data (for the
      first 72 h) were prospectively collected on all 18 WFVs, and compared to those of
      36 RBPs matched 2:1 for age, gender, burns severity (total body surface area
      >=20%) and ICU admission. We found that WFVs had more positive cultures overall
      (10/18 [56%] vs 7/36 [19%], p=0.04), and we cultured more Gram negative bacteria
      from wounds (11/13 [85%] vs 3/12 [25%], p=0.005). Although WFVs were more likely
      to culture Enterobacteriaceae (5/18 vs 2/36) and Aeromonas spp. (3/18 vs 1/36),
      and less likely to culture Staphylococcus aureus (2/18 vs 6/36), these
      differences were not statistically significant. Given the predominance of Gram
      negative organisms cultured from WFVs, our routine burn wound prophylaxis
      (intravenous cephazolin) would have been inadequate in the WFV group. We suggest
      that an alternative regimen of oxacillin/nafcillin/flucloxacillin plus gentamicin
      (or a fluoroquinolone if renal impairment present) may be more appropriate for
      burn wound prophylaxis in this complex group of patients.

PMID- 22871556
TI  - Patient HLA-DP-specific CD4+ T cells from HLA-DPB1-mismatched donor lymphocyte
      infusion can induce graft-versus-leukemia reactivity in the presence or absence
      of graft-versus-host disease.
AB  - Clinical studies have demonstrated that HLA-DPB1-mismatched allogeneic stem cell
      transplantation (allo-SCT) is associated with a decreased risk of disease relapse
      and an increased risk of graft-versus-host disease (GVHD) compared with HLA-DPB1
      matched SCT. In T cell-depleted allo-SCT, mismatching of HLA-DPB1 was not
      associated with an increased risk of severe GVHD, but a significant decreased
      risk of disease relapse was still observed. To investigate whether patient HLA-DP
      specific CD4(+) T cell responses were frequently induced after T cell-depleted
      HLA-DPB1-mismatched allo-SCT and donor lymphocyte infusion (DLI), we developed a
      method to screen for the presence of HLA-DP-specific CD4(+) T cells using CD137
      as an activation marker and analyzed 24 patient-donor combinations. The patients
      suffered from various B cell malignancies, multiple myeloma, and myeloid
      leukemias. Patient HLA-DP-specific CD4(+) T cells were detected after DLI in 13
      of 18 patients who exhibited a clinical response to DLI, compared with only 1 of
      6 patients without a clinical response to DLI. Eight patients developed
      significant GVHD. These data show that patient HLA-DP-specific CD4(+) T cells
      frequently occur after HLA-DPB1-mismatched T cell-depleted allo-SCT and DLI, and
      are associated with graft-versus-leukemia reactivity both in the presence and
      absence of GVHD.

PMID- 22871557
TI  - High alloreactivity of low-dose prophylactic donor lymphocyte infusion in
      patients with acute leukemia undergoing allogeneic hematopoietic cell
      transplantation with an alemtuzumab-containing conditioning regimen.
AB  - The value of prophylactic donor lymphocyte infusion (pDLI) is unclear and differs
      among diseases and transplantation protocols. Experience with this approach in
      patients with acute leukemia undergoing hematopoietic cell transplantation (HCT)
      with an alemtuzumab-incorporating conditioning protocol is lacking. We conducted
      a single-center prospective study to investigate the applicability and efficacy
      of prophylactic donor lymphocyte infusion (pDLI) in patients with leukemia
      undergoing HCT with a low-dose alemtuzumab-containing conditioning regimen.
      Inclusion criteria were high-risk acute myelogenous leukemia, acute lymphoblastic
      leukemia, or increasing mixed chimerism. All patients included were tapered off
      of immunotherapy. Exclusion criteria were a history of >= grade II or active
      graft-versus-host disease (GVHD). Of the 56 consecutive patients who underwent
      HCT with an alemtuzumab-containing regimen, 15 patients (8 with acute myelogenous
      leukemia and 7 with acute lymphoblastic leukemia) met the study inclusion
      criteria and received prophylactic DLI (total of 45 infusions) from 7 sibling
      donors and 8 unrelated donors. The first infusion was given at a median of 162
      days posttransplantation. The median number of DLIs was 3, and the median
      cumulative CD3(+) cell dose was 2 * 10(6)cells/kg. Six of the 8 patients (75%)
      who received pDLI while in mixed chimerism converted to stable, complete donor
      chimerism. Some 47% of DLI recipients developed GVHD (4 acute GVHD and 3 with
      chronic GVHD) after a median cumulative dose of 2 * 10(6) CD3(+) cells/kg. After
      a median follow-up of 575 days, 11 (73%) pDLI recipients were alive. All 4 deaths
      were due to GVHD-related causes. None of the patients who received pDLIs
      relapsed. Patients with leukemia who received low-dose pDLI after conditioning
      with alemtuzumab are at low risk for relapse; however, this approach is
      associated with a relatively high incidence of severe GVHD.

PMID- 22871558
TI  - Canonical correlation analysis of synchronous neural interactions and cognitive
      deficits in Alzheimer's dementia.
AB  - In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on
      the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as
      a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on
      the application of canonical correlation analysis to investigate the relations
      between SNI and cognitive neuropsychological (NP) domains in AD patients. First,
      we performed individual correlations between each SNI and each NP, which provided
      an initial link between SNI and specific cognitive tests. Next, we performed
      factor analysis on each set, followed by a canonical correlation analysis between
      the derived SNI and NP factors. This last analysis optimally associated the
      entire MEG signal with cognitive function. The results revealed that SNI as a
      whole were mostly associated with memory and language, and, slightly less,
      executive function, processing speed and visuospatial abilities, thus
      differentiating functions subserved by the frontoparietal and the temporal
      cortices. These findings provide a direct interpretation of the information
      carried by the SNI and set the basis for identifying specific neural disease
      phenotypes according to cognitive deficits.

PMID- 22871559
TI  - Botulinum injection for the management of myofascial pain in the masticatory
      muscles. A prospective outcome study.
AB  - We prospectively analysed the outcome after botulinum injection in patients who
      did not recover after conservative measures to manage masticatory myofascial
      pain, and who were not willing to take low dose tricyclic antidepressants as a
      muscle relaxant. We prospectively 62 patients were assessed with visual analogue
      scores (VAS) for pain on the affected side before, and 6 weeks after botulinum
      injection(s) (50 units Dysport in up to 3 sites), and measured mouth opening in
      mm. Of those treated 49 (79%) showed at least some improvement (pain reduced by
      more than 25%). Patients reported more than a 90% reduction in the VAS for 25
      (30%) of the 84 sides of the face treated. Only 22 of the 62 patients had more
      than one course of treatment to the same side. Interincisal distance improved by
      a mean/median of 0.9 mm (p<0.03) after treatment. Side effects included 3 cases
      of temporary weakness of a facial muscle. Ranking the VAS pain scores using the
      Wilcoxon test before and after injection showed a significant reduction in pain
      (median change -29.5, interquartile range -53 to -16, p<0.0001). The treatment
      significantly improved patients' pain scores and the overall mean/median
      reduction in pain was 57%. Botulinum injection does not guarantee complete
      resolution of myofascial pain, but it usually has some beneficial effect in
      improving the symptoms, and should be considered as an alternate treatment for
      masticatory myofascial pain if conservative methods have failed.

PMID- 22871560
TI  - Phase behavior of itraconazole-phenol mixtures and its pharmaceutical
      applications.
AB  - The aims of this study were to examine the phase behavior of itraconazole-phenol
      mixtures and assess the feasibility of topical formulations of itraconazole using
      eutectic mixture systems. Itraconazole-phenol eutectic mixtures were
      characterized using differential scanning calorimetry, Fourier transform infrared
      spectroscopy, (1)H-nuclear magnetic resonance, and powder X-ray diffractometry.
      The skin permeation rates of itraconazole-phenol eutectic formulations were
      determined using Franz diffusion cells fitted with excised hairless mouse skins.
      Itraconazole can form eutectic compounds with phenol, and the hydrogen-bonding
      interactions between the carbonyl group in the itraconazole and hydroxyl group in
      phenol play a major role in itraconazole-phenol eutectic formation. Despite its
      high molecular weight and hydrophobicity, the drug (i.e., itraconazole) can be
      permeated through excised hairless mouse skins from itraconazole-phenol eutectic
      formulations. The findings of this study emphasize the capabilities of the
      topical application of itraconazole via external preparations.

PMID- 22871561
TI  - Formation of drug/surfactant catanionic vesicles and their application in
      sustained drug release.
AB  - The aggregation behavior of the cationic drug/anionic surfactant vesicles formed
      by tetracaine hydrochloride (TH) and double-chain surfactant, sodium bis(2
      ethylhexyl)sulfosuccinate (AOT), was investigated. By controlling the molar ratio
      of TH to AOT, a transition from catanionic vesicles to micelles was observed. The
      catanionic aggregates exhibited different charge properties, structures,
      interaction enthalpies and drug release behaviors depending on the composition.
      To characterize the cationic drug/anionic surfactant system, transmission
      electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration
      calorimetry (ITC), conductivity, turbidity and zeta potential (zeta) measurements
      were performed. The drug release results indicate that the present drug
      containing catanionic vesicles have promising applications in drug delivery
      systems. Furthermore, the percentage of drug distributed in the catanionic
      vesicles or micelles can be obtained by comparing the cumulative release of the
      corresponding aggregates with the pure drug solution.

PMID- 22871562
TI  - Establishment of cocrystal cocktail grinding method for rational screening of
      pharmaceutical cocrystals.
AB  - Cocrystals (CCs) used in the pharmaceutical industry are defined as complex
      crystals formed by reaction between an API and a cocrystal former (CCF); unlike
      salts, CCs do not show proton transfer. Recently, pharmaceutical CCs have been
      used to improve the drug-likeness of APIs, such as solubility and stability.
      Grinding is more effective for CC synthesis than crystallization from solution
      because in the former case, the API can predominantly interact with the CCF
      without being affected by solvents. However, this method is tedious because the
      API is ground with only one CCF at a time. We developed a cocktail cocrystal
      grinding (CCG) method, in which a mixture of CCFs having the same functional
      group was used. No false negatives/positives were observed in CCG when
      carbamazepine was used as the model compound. This method could be used to obtain
      CCs of piroxicam and spironolactone. False negatives were observed for only one
      compound from among three model compounds, indicating that CCG facilitates
      efficient CC detection and that it has higher throughput than does the
      conventional method. Further, CCG is fast and suitable for rational CC screening,
      and it helps identify the partial structure of CCFs that forms synthons with an
      API.

PMID- 22871563
TI  - Wind of change challenges toxicological regulators.
AB  - BACKGROUND: In biomedical research, the past two decades have seen the advent of
      in vitro model systems based on stem cells, humanized cell lines, and engineered
      organotypic tissues, as well as numerous cellular assays based on primarily
      established tumor-derived cell lines and their genetically modified derivatives.
      OBJECTIVE: There are high hopes that these systems might replace the need for
      animal testing in regulatory toxicology. However, despite increasing pressure in
      recent years to reduce animal testing, regulators are still reluctant to adopt in
      vitro approaches on a large scale. It thus seems appropriate to consider how we
      could realistically perform regulatory toxicity testing using in vitro assays
      only. DISCUSSION AND CONCLUSION: Here, we suggest an in vitro-only approach for
      regulatory testing that will benefit consumers, industry, and regulators alike.

PMID- 22871564
TI  - Long-term systemic right ventricular support in transposition and dextrocardia.

PMID- 22871565
TI  - Angiographic outcomes of radial artery versus saphenous vein in coronary artery
      bypass graft surgery: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: The efficacy of coronary artery bypass graft (CABG) surgery for
      patients with ischemic heart disease is dependent on the patency of the selected
      conduit. The left internal thoracic artery is considered to be the best conduit
      for CABG. However, the preferred conduit between the radial artery (RA) and
      saphenous vein (SV) remains controversial. The present meta-analysis aims to
      establish the current level IA evidence on patency outcomes comparing the RA and
      SV. METHODS: Electronic searches were performed using 6 databases from their
      inception to March 2012. Two reviewers independently identified all relevant
      randomized controlled trials (RCTs) comparing patency outcomes of RA and SV
      grafts after CABG. Data were extracted and meta-analyzed according to
      angiographic end points at specified follow-up intervals. RESULTS: Five relevant
      RCTs were identified for inclusion in the present meta-analysis. Angiographic
      results indicated that the RA was significantly more likely to be completely
      patent and less likely to be associated with graft failure or complete occlusion
      at 4 years' follow-up and beyond. However, the RA was significantly more likely
      to be associated with string sign at 1 year of follow-up. CONCLUSIONS: While
      acknowledging the limitations of heterogeneous surgical techniques, results from
      the present meta-analysis suggest potential superiority of the RA compared with
      the SV at midterm angiographic follow-up. However, the increased incidence of
      string sign associated with the RA is of potential clinical concern. Further
      research should be directed at correlating angiographic findings of string sign
      and graft failure to clinical symptoms and major adverse cardiac and
      cerebrovascular events at long-term follow-up.

PMID- 22871566
TI  - Clinical and echocardiographic outcomes after surgery for severe isolated
      tricuspid regurgitation.
AB  - OBJECTIVE: Few studies have investigated the outcomes after surgical correction
      of severe isolated tricuspid regurgitation. METHODS: The medical records of 51
      consecutive patients (aged 55.8 +/- 12.9 years, 25 male) who underwent tricuspid
      valve surgery at the Asan Medical Center between September 1996 and July 2010
      were evaluated retrospectively. All patients had severe isolated tricuspid
      regurgitation but no significant left-sided cardiac disease or history of heart
      surgery. RESULTS: Tricuspid valve repair (n = 37, 72.5%) or replacement (n = 14,
      27.5%) was performed. Replacement involved mechanical (n = 4) or bioprosthetic
      valves (n = 10). One early death occurred (2.0%). During a median follow-up
      period of 47.4 months (interquartile range, 10.4-61.4 months), 9 late deaths, 3
      readmissions for congestive heart failure, 2 heart transplantations, and 1
      tricuspid valve reoperation occurred. Overall and event-free survivals at 5 years
      were 83.5% +/- 5.4% and 77.3% +/- 6.1%, respectively. In the multivariable Cox
      regression analysis, preoperative hemoglobin (P = .045), serum bilirubin (P =
      .008), estimated glomerular filtration rate (P = .045), and systolic right
      ventricular dimension (P = .047) were significant and independent determinants of
      clinical outcome. On serial echocardiographic evaluations (median follow-up
      period, 28.5 months; interquartile range, 18.9-68.7 months), moderate-to-severe
      tricuspid regurgitation was detected in 21 patients (41%). Severe tricuspid
      regurgitation after tricuspid valve repair or bioprosthetic valve replacement was
      a significant predictor of poor event-free survival, even after adjustment for
      preoperative risk factors (P = .036). CONCLUSIONS: In the present cohort,
      preoperative anemia, renal/hepatic dysfunction, right ventricular dilatation, and
      significant postoperative tricuspid regurgitation were associated with poor
      outcomes. Timely surgery is advisable in patients with severe isolated tricuspid
      regurgitation before the development of anemia, organ dysfunction, or right
      ventricular dilatation.

PMID- 22871567
TI  - LRP6 mediates Wnt/beta-catenin signaling and regulates adipogenic differentiation
      in human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSC) are subjected to the control of several
      signal transduction pathways during regeneration processes, whereby Wnt/beta
      catenin signaling is of pivotal importance. Since there exists only fragmentary
      knowledge concerning the molecular function of the Wnt-coreceptors LRP5 and LRP6
      (low-density lipoprotein receptor-related protein) in hMSC, we studied their
      impact on Wnt/beta-catenin signal transduction by RNA interference. For
      monitoring changes in beta-catenin-dependent transcription in a highly sensitive
      and specific manner, hMSC were stably transfected with a TCF/LEF reporter gene
      plasmid. In the presence of the activator Wnt3a, knockdown of LRP6 led to a
      strong decreased Wnt/beta-catenin signaling, while RNAi against LRP5 exhibited no
      effect in this setting. In a reverse approach, ectopic expression of LRP6
      resulted in a strong enhancement of Wnt/beta-catenin signaling, whereas
      overexpression of LRP5 exhibited no increased signaling capacity. Furthermore,
      only the ectopic expression of LRP6--but not that of LRP5--was able to restore
      Wnt3a-mediated beta-catenin signaling after knockdown of endogenously expressed
      LRP6. These results demonstrate LRP6 as the predominant Wnt3a LRP-receptor in
      hMSC, which cannot be substituted by LRP5. In addition, we observed enhanced
      differentiation toward the adipogenic lineage after RNAi against LRP6 which was
      associated with the induction of PPAR-gamma and fat vacuole formation. Thus, LRP6
      is not only indispensable for Wnt3a/beta-catenin signaling, but also for the
      suppression of differentiation of hMSC into the adipogenic lineage. Based on
      these observations, LRP6 may represent an attractive drug target for manipulating
      hMSC in cell and tissue regeneration approaches.

PMID- 22871568
TI  - Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by
      retinoic acid in HepG2 cells.
AB  - The vitamin A derivative retinoic acid (RA) is an important regulator of
      mammalian adiposity and lipid metabolism, primarily acting at the gene expression
      level through nuclear receptors of the RA receptor (RAR) and retinoid X receptor
      (RXR) subfamilies. Here, we studied cell-autonomous effects of RA on fatty acid
      metabolism, particularly fatty acid oxidation, in human hepatoma HepG2 cells.
      Exposure to all-trans RA (ATRA) up-regulated the expression of carnitine
      palmitoyl transferase-1 (CPT1-L) in HepG2 cells in a dose- and time-dependent
      manner, and increased cellular oxidation rate of exogenously added radiolabeled
      palmitate. The effect of ATRA on gene expression of CPT1-L was: dependent on
      ongoing transcription, reproduced by both 9-cis RA and a pan-RXR agonist (but not
      a pan-RAR agonist) and abolished following RXRalpha partial siRNA-mediated
      silencing. CPT1-L gene expression was synergistically induced in HepG2 cells
      simultaneously exposed to ATRA and a selective peroxisome proliferator-activated
      receptor alpha agonist. We conclude that ATRA treatment enhances fatty acid
      catabolism in hepatocytes through RXR-mediated mechanisms that likely involve the
      transactivation of the PPARalpha:RXR heterodimer. Knowledge of agents and
      nutrient-derivatives capable of enhancing substrate oxidation systemically and
      specifically in liver, and their mechanisms of action, may contribute to new
      avenues of prevention and treatment of fatty liver, obesity and other metabolic
      syndrome-related disorders.

PMID- 22871569
TI  - An active mitochondrial biogenesis occurs during dendritic cell differentiation.
AB  - Dendritic cells (DC) are sentinels of the immune system deriving from circulating
      monocyte precursors recruited to sites of inflammation. In a previous report (Del
      Prete et al., 2008) we showed that, after differentiation, DC exhibited increased
      number of condensed mitochondria and dynamic changes in their energy metabolism.
      A study is presented here showing that the DC differentiation process is
      characterized by increased expression level and activity of mitochondrial
      respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy
      number. Moreover, DC are equipped with more efficient antioxidant protection
      systems, over expressed most likely to detoxify increased ROS production, as a
      consequence of the much higher mitochondrial activity. Kinetic analysis of the
      three main mitochondrial biogenesis-associated genes revealed that the peak in
      PPARgamma coactivator-1alpha (PGC-1alpha) gene expression was suddenly reached
      few hours after the onset of the differentiation. While PGC-1alpha expression
      rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear
      respiratory factor-1 (NRF-1) expression gradually increased. These findings
      demonstrate that an active mitochondrial biogenesis occurs during DC
      differentiation and further suggest that an early input by the master regulator
      of mitochondrial biogenesis PGC-1alpha is needed to trigger the subsequent
      activation of the downstream transcription factors, NRF-1 and TFAM in this
      process.

PMID- 22871570
TI  - Caenorhabditis elegans vulval cell fate patterning.
AB  - The spatial patterning of three cell fates in a row of competent cells is
      exemplified by vulva development in the nematode Caenorhabditis elegans. The
      intercellular signaling network that underlies fate specification is well
      understood, yet quantitative aspects remain to be elucidated. Quantitative models
      of the network allow us to test the effect of parameter variation on the cell
      fate pattern output. Among the parameter sets that allow us to reach the wild
      type pattern, two general developmental patterning mechanisms of the three fates
      can be found: sequential inductions and morphogen-based induction, the former
      being more robust to parameter variation. Experimentally, the vulval cell fate
      pattern is robust to stochastic and environmental challenges, and minor variants
      can be detected. The exception is the fate of the anterior cell, P3.p, which is
      sensitive to stochastic variation and spontaneous mutation, and is also evolving
      the fastest. Other vulval precursor cell fates can be affected by mutation, yet
      little natural variation can be found, suggesting stabilizing selection. Despite
      this fate pattern conservation, different Caenorhabditis species respond
      differently to perturbations of the system. In the quantitative models, different
      parameter sets can reconstitute their response to perturbation, suggesting that
      network variation among Caenorhabditis species may be quantitative. Network
      rewiring likely occurred at longer evolutionary scales.

PMID- 22871571
TI  - GAB2--a scaffolding protein in cancer.
AB  - Adaptor or scaffolding proteins mediate protein-protein interactions that drive
      the formation of protein complexes. Grb2-associated binding protein 2 (GAB2)
      scaffolding protein is an intermediary molecule that links plasma membrane
      receptor signaling including receptor tyrosine kinases with the downstream
      effectors, such as protein tyrosine phosphatase, nonreceptor type 11 (SHP2), p85
      subunit of phosphoinositide-3 kinase (PI3-K), phospholipase C-gamma 1 (PLC
      gamma), v-crk sarcoma virus CT10 (CRK), Src homology 2 domain containing
      transforming protein 1 (SHC), and SH2 containing inositol phosphatase (SHIP).
      Although, well described in signal transduction, its role in cancer has recently
      been emerging especially in leukemia, breast and ovarian cancer, and melanoma.
      GAB2 is essential for two major signal transduction pathways in cancer, the PI3-K
      AKT and extracellular signal-regulated kinase (ERK) signaling pathways, and thus
      regulates a number of key cellular processes. This review focuses on structure
      and function of GAB2, its regulatory proteins, emerging role in cancer, and
      potential as a therapeutic target.

PMID- 22871572
TI  - KRAS(G12D)- and BRAF(V600E)-induced transformation of murine pancreatic
      epithelial cells requires MEK/ERK-stimulated IGF1R signaling.
AB  - Mutation of KRAS is a common initiating event in pancreatic ductal adenocarcinoma
      (PDAC). Yet, the specific roles of KRAS-stimulated signaling pathways in the
      transformation of pancreatic ductal epithelial cells (PDEC), putative cells of
      origin for PDAC, remain unclear. Here, we show that KRAS(G12D) and BRAF(V600E)
      enhance PDEC proliferation and increase survival after exposure to apoptotic
      stimuli in a manner dependent on MEK/ERK and PI3K/AKT signaling. Interestingly,
      we find that activation of PI3K/AKT signaling occurs downstream of MAP-ERK kinase
      (MEK), and is dependent on the autocrine activation of the insulin-like growth
      factor (IGF) receptor (IGF1R) by IGF2. Importantly, IGF1R inhibition impairs
      KRAS(G12D)- and BRAF(V600E)-induced survival, whereas ectopic IGF2 expression
      rescues KRAS(G12D)- and BRAF(V600E)-mediated survival downstream of MEK
      inhibition. Moreover, we show that KRAS(G12D)- and BRAF(V600E)-induced tumor
      formation in an orthotopic model requires IGF1R. Interestingly, we show that
      while individual inhibition of MEK or IGF1R does not sensitize PDAC cells to
      apoptosis, their concomitant inhibition reduces survival. Our findings identify a
      novel mechanism of PI3K/AKT activation downstream of activated KRAS, illustrate
      the importance of MEK/ERK, PI3K/AKT, and IGF1R signaling in pancreatic tumor
      initiation, and suggest potential therapeutic strategies for this malignancy.

PMID- 22871575
TI  - A quantitative x-ray detection system for gold nanoparticle tumour biomarkers.
AB  - X-ray fluorescence techniques have proven beneficial for identifying and
      quantifying trace elements in biological tissues. A novel approach is being
      developed that employs x-ray fluorescence with an aim to locate heavy
      nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles
      can be functionalized to act as markers for tumour characteristics to map the
      disease state, with the future aim of imaging them to inform cancer therapy
      regimes. The uptake of functionalized nanoparticles by cancer cells will also
      enable detection of small clusters of infiltrating cancer cells which are
      currently missed by commonly used imaging modalities. The novel system,
      consisting of an energy-resolving silicon drift detector with high spectral
      resolution, shows potential in both quantification of and sensitivity to
      nanoparticle concentrations typically found in tumours. A series of synchrotron
      measurements are presented; a linear relationship between fluorescence intensity
      and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1),
      the detection limit of the system. Successful use of a bench-top source, suitable
      for possible future clinical use, is also demonstrated, and found not to degrade
      the detection limit or accuracy of the GNP concentration measurement. The
      achieved system sensitivity suggests possible future clinical usefulness in
      measuring tumour uptake in vivo, particularly in shallow tumour sites and small
      animals, in ex vivo tissue and in 3D in vitro research samples.

PMID- 22871573
TI  - Generation of isogenic D4Z4 contracted and noncontracted immortal muscle cell
      clones from a mosaic patient: a cellular model for FSHD.
AB  - In most cases facioscapulohumeral muscular dystrophy (FSHD) is caused by
      contraction of the D4Z4 repeat in the 4q subtelomere. This contraction is
      associated with local chromatin decondensation and derepression of the DUX4
      retrogene. Its complex genetic and epigenetic cause and high clinical variability
      in disease severity complicate investigations on the pathogenic mechanism
      underlying FSHD. A validated cellular model bypassing the considerable
      heterogeneity would facilitate mechanistic and therapeutic studies of FSHD.
      Taking advantage of the high incidence of somatic mosaicism for D4Z4 repeat
      contraction in de novo FSHD, we have established a clonal myogenic cell model
      from a mosaic patient. Individual clones are genetically identical except for the
      size of the D4Z4 repeat array, being either normal or FSHD sized. These clones
      retain their myogenic characteristics, and D4Z4 contracted clones differ from the
      noncontracted clones by the bursts of expression of DUX4 in sporadic nuclei,
      showing that this burst-like phenomenon is a locus-intrinsic feature.
      Consequently, downstream effects of DUX4 expression can be observed in D4Z4
      contracted clones, like differential expression of DUX4 target genes. We also
      show their participation to in vivo regeneration with immunodeficient mice,
      further expanding the potential of these clones for mechanistic and therapeutic
      studies. These cell lines will facilitate pairwise comparisons to identify FSHD
      specific differences and are expected to create new opportunities for high
      throughput drug screens.

PMID- 22871574
TI  - Determination of severity of murine IgA nephropathy by glomerular complement
      activation by aberrantly glycosylated IgA and immune complexes.
AB  - The pathogenic roles of glomerular deposition of components of the complement
      cascade in IgA nephropathy (IgAN) are not completely clarified. To investigate
      the pathologic role of complement pathways in IgAN, two IgAN-prone mouse models
      were examined. Grouped ddY (gddY) mice showed significant high proteinuria,
      severe glomerular lesions, and extracellular matrix expansion compared with high
      serum IgA (HIGA) mice but with similar intensity of glomerular IgA deposition.
      Glomerular activation of the classical, lectin, and alternative pathways was
      demonstrated by significantly stronger staining for complement (C)3, C5b-9, C1q,
      C4, mannose-binding lectin (MBL)-A/C, MBL-associated serine protease-2, and
      factor B and properdin in gddY mice than in HIGA mice. Similarly, the serum
      levels of IgA-IgG2a/IgM and IgA-MBL-A/C immune complexes and polymeric IgA were
      significantly higher in gddY mice than in HIGA mice. Moreover, the serum levels
      of aberrantly glycosylated IgA characterized by the binding of Sambucus nigra
      bark lectin and Ricinus communis agglutinin I were significantly higher in gddY
      mice than in HIGA mice. This aberrancy in glycosylation was confirmed by
      monosaccharide compositional analysis of purified IgA using gas-liquid
      chromatography. This study is the first to demonstrate that aberrantly
      glycosylated IgA may influence the formation of macromolecular IgA including IgA
      IgG immune complexes and subsequent complement activation, leading to full
      progression of IgAN.

PMID- 22871576
TI  - Novel link between inflammation and impaired glucose transport during equine
      insulin resistance.
AB  - Although insulin resistance (IR) has been increasingly recognized in horses, a
      clear understanding of its pathophysiology is lacking. The purpose of the present
      study was to determine the early pathologic changes in IR horses by
      characterizing alterations in proteins that play key roles in innate
      immunological responses and inflammatory pathways, and by identifying potential
      links with glucose transport and insulin signaling. Visceral (VIS) and
      subcutaneous (SC) adipose tissue and skeletal muscle (SM) biopsies were collected
      from horses, which were classified as insulin-sensitive (IS) or IR based on the
      results of an insulin-modified frequently sampled intravenous glucose tolerance
      test. Protein expression of Toll-like receptor 4 (TLR-4), suppressor of cytokine
      signaling 3 (SOCS-3) and tumor necrosis factor alpha (TNF-alpha) were quantified
      by Western blotting in VIS and SC adipose depots and SM, as well as insulin
      receptor substrate 1 (IRS-1). To better characterize the potential relationship
      between inflammation, IR and impaired glucose transport, we correlated active
      cell surface glucose transporter 4 (GLUT-4) content (measured by a cell surface
      biotinylated assay) with individual- and tissue-specific data related to
      inflammation. IR was associated with a significantly increased expression of TLR
      4 and SOCS-3 in SM and VIS tissue, without a significant change in SC site. We
      also observed a significant increase in TNF-alpha in VIS, but not in SC, tissue
      of IR vs. IS horses. There was no difference in total content or serine
      phosphorylation of IRS-1 for any sampling site in IR compared to IS horses. We
      further observed a significant positive correlation between TLR-4 content and
      SOCS-3, as well as a significant negative correlation between SOCS-3 content and
      GLUT-4 trafficking. Taken together, the data suggested a pro-inflammatory state
      in SM and VIS, but not SC, adipose depot during compensated IR. In addition, SOCS
      3 appears to be a novel link between inflammation and dysregulated glucose
      metabolism and insulin sensitivity during the early pathogenesis of insulin
      resistance.

PMID- 22871577
TI  - Immune responses associated with progression and control of infection in calves
      experimentally challenged with Mycobacterium avium subsp. paratuberculosis.
AB  - This study examined the immune responses related to the infection, progression
      and control of Mycobacterium avium subsp. paratuberculosis (MAP) infection in
      calves. Twenty calves were challenged orally with MAP and 11 non-challenged
      calves served as controls. Approximately half the calves from each group were
      sacrificed at either 7 or 15 months post-challenge (PC). The majority of the
      challenged calves (19/20) shed MAP in feces 2-4 months PC, but thereafter fecal
      shedding reduced markedly. The severity of infection was reduced at 15 months PC
      compared to that at 7 months PC as seen from a significantly lower isolation of
      MAP from tissues and lower lesion scores (P<0.05). In addition, there was a
      reduction in the upregulation of gene expression of gamma interferon, interleukin
      10 (IL-10) and inducible nitric oxide synthase from the antigen-stimulated
      mesenteric lymph node (MLN) cultures of the challenged calves. No evidence of
      infection was detected in the control calves. The severity of the infection in
      individual calves at 15 months PC as indicated from the number of tissue culture
      positive sites, was negatively related to IL-10 released from antigen-stimulated
      peripheral blood mononuclear cells (P<0.05). Collectively the data indicated that
      the severity of the MAP infection was reduced in the calves at 15 months PC and
      in a specific time period during infection, IL-10 may play a role in reducing the
      severity of this disease.

PMID- 22871578
TI  - High-affinity and selective dopamine D3 receptor full agonists.
AB  - We have designed, synthesized and evaluated a series of new compounds with the
      goal to identify potent and selective D(3) ligands. The two most potent and
      selective new D(3) ligands are compounds 38 and 52, which bind to the D(3)
      receptors with a K(i) value of <nM and display a selectivity of 450-494 times
      over the D(2) receptors and >10,000 times over the D(1) receptors. Both 38 and 52
      are full agonists with high potency at the D(3) receptor in a D(3) functional
      assay.

PMID- 22871579
TI  - Pd-mediated functionalization of polysubstituted pyrroles: their evaluation as
      potential inhibitors of PDE4.
AB  - Novel polysubstituted pyrroles have been designed and accessed via a one-pot
      multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All
      the compounds synthesized were tested for their PDE4B inhibitory properties in
      vitro and two of them obtained via Heck reaction showed significant inhibition.
      The docking results suggested that these alkenyl derivatives containing ester
      moiety interact well with the PDE4B protein in silico where the ester carbonyl
      oxygen played a key role. The pyrrole framework presented here could be a new
      template for the identification of small molecule based novel inhibitors of PDE4.
      The single crystal X-ray data of a representative compound is presented.

PMID- 22871580
TI  - Near-infrared fluorescent divalent RGD ligand for integrin alphavbeta3-targeted
      optical imaging.
AB  - A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate
      [c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing
      two carboxylic acid groups (cypate) for integrin alpha(v)beta(3)-targeting.
      Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited
      remarkable improvements in integrin alpha(v)beta(3) binding affinity and tumor
      uptake in nude mice of A549. The results suggest that cypate-linked divalent
      ligands can serve as an important molecular platform for exploring receptor
      targeted optical imaging and treatment of various diseases.

PMID- 22871581
TI  - Homodimeric SV40 NLS peptide formed by disulfide bond as enhancer for gene
      delivery.
AB  - Recently, cysteine residue incorporation increased liposome-mediated transfection
      compared to unmodified peptide. Therefore, we designed novel modified SV40 NLS
      peptides, homodimeric (NLS-CTHD, NLS-NTHD) and closed structure (cyclic NLS),
      simply using disulfide bond between cysteines to develop more efficient and safe
      non-viral gene delivery system. The simple mix of NLS-CTHD among these novel
      transfection enhancing peptides with DNA increased the gene transfer potency of
      cationic liposomes more efficiently with no additional cytotoxicity.

PMID- 22871582
TI  - Design, synthesis, and structure-activity relationships of a series of 2-Ar-8
      methyl-5-alkylaminoquinolines as novel CRF1 receptor antagonists.
AB  - We designed and synthesized a series of 2-Ar-8-methyl-5-alkylaminolquinolines as
      potent corticotropin-releasing factor 1 (CRF(1)) receptor antagonists. The
      structure-activity relationships of substituents at each position (R(3), R(5),
      R(5'), and R(8)) was investigated. By derivatization, three compounds (6, 14b,
      and 14c) were identified as orally active CRF(1) receptor antagonists.

PMID- 22871583
TI  - Long-term electrical survival analysis of Riata and Riata ST silicone leads:
      National Veterans Affairs experience.
AB  - BACKGROUND: A medical device advisory issued by St Jude Medical in November 2011
      estimated 0.63% all-cause abrasion rate on their Riata and Riata ST silicone high
      voltage lead families (Riata/ST), leading to Food and Drug Administration class I
      recall. We performed an independent comparative, long-term electrical survival
      analysis of Riata/ST and 3 other high-voltage lead families in a large national
      cohort of patients. OBJECTIVE: To evaluate long-term electrical survival of
      Riata/ST leads relative to other commonly evaluated high-voltage leads. METHODS:
      Failure rates of Riata/ST, Sprint Quattro Secure (Quattro), Sprint Fidelis
      (Fidelis), and Endotak Reliance G/SG (Endotak) leads from the Veterans
      Administration's National Cardiac Device Surveillance Center database, consisting
      of 24,145 patients with remote transmissions since 2003, were analyzed. Survival
      Probabilities were determined with Kaplan-Meier survival analysis and compared
      using the log-rank test. RESULTS: Of 1,403 Riata/ST, 6,091 Quattro, 5,073
      Fidelis, and 2,401 Endotak leads identified, 5-year survival probability of
      Riata/ST leads (97.5%) was significantly lower than that of Quattro (99.3%) and
      Endotak (99.4%) leads (P <.0001) but higher than that of Fidelis leads (89.6%) (P
      <.0001). Riata ST leads showed a 5-year survival of 95.5% (95% confidence
      interval 92.4-97.4) compared to 98.4% (95% confidence interval 97.1-99.1) in
      Riata leads (P = .003). CONCLUSIONS: There is decreased survival probability of
      Riata/ST leads compared to other contemporary high-voltage leads, with decreased
      survival of Riata ST silicone compared to Riata lead series. Careful long-term
      follow-up should be maintained in patients with Riata/ST leads in order to
      prevent inappropriate shocks or failed device interventions. Our results were
      determined in advance of Food and Drug Administration class I recall, which
      suggested that large-scale remote monitoring may be an effective tool for
      continued implantable cardioverter-defibrillator system surveillance.

PMID- 22871584
TI  - Effect of straw on lamb welfare, production performance and meat quality during
      the finishing phase of fattening.
AB  - The studies analyse the effect of straw on lamb welfare, production and meat
      quality in finishing lambs. Two studies were carried out. Study 1 included two
      treatments and two replicates with six lambs each (17.20+/-0.2 kg). One pen was
      provided with straw for forage and bedding while the other had none. Feeding with
      concentrate was ad libitum. Live weight and concentrate consumption were recorded
      and average daily gain and conversion index calculated. Stereotypes, agonistic
      and affiliative interactions and physiological indicators of stress were
      analysed. In study 2, 24 lambs were divided into two groups to analyse the effect
      of treatments on meat and carcass quality. No significant differences in
      production or meat quality traits were observed. Lambs housed without straw had
      higher levels of cortisol and stereotypes. Affiliative interactions were greater
      in lambs without straw. Results suggest that straw can be considered an effective
      environment-enriching tool to improve welfare.

PMID- 22871585
TI  - Compatibility art of traditional Chinese medicine: from the perspective of herb
      pairs.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Over the past decades, research of traditional
      Chinese medicine (TCM) mainly focused on developing potential candidates from
      Chinese medicinal herbs, while the wisdom of applying these traditional herbs has
      not been paid as much attention as it deserves. As is well-known, multi-herb
      therapy is one of the most important characteristics of TCM, but the
      modernization drive of this conventional wisdom has faced many obstacles due to
      its unimaginable complexity. Herb pairs, the most fundamental and the simplest
      form of multi-herb formulae, are a centralized representative of Chinese herbal
      compatibility. In light of their simplicity and the basic characteristics of
      complex formulae, herb pairs are of great importance in the studies of herb
      compatibility. MATERIALS AND METHODS: A systematic search of herb pair related
      research was carried out using multiple online literature databases, books and
      monographs published in the past 20 years. RESULTS: A comprehensive introduction
      to the compatibility of TCM, the position of herb pairs in TCM and the progresses
      of several famous herb pairs were provided in this review. Furthermore, the
      clinical study and the future research trends of herb pairs were also discussed.
      CONCLUSIONS: Herb pairs have played, and may continue to play a key role in full
      investigation of general herb compatibility for their indispensable position in
      TCM. Much more research is needed for the standardization, safety evaluation, and
      mechanism exploration of herb pairs.

PMID- 22871587
TI  - A descriptive study of sexual homicide in Canada: implications for police
      investigation.
AB  - Few empirical studies have been conducted that examine the phenomenon of sexual
      homicide, and among these studies, many have been limited by small sample size.
      Although interesting and informative, these studies may not be representative of
      the greater phenomenon of sexual murder and may be subject to sampling bias that
      could have significant effects on results. The current study aims to provide a
      descriptive analysis of the largest sample of sexual homicide cases across Canada
      in the past 62 years. In doing so, the study aims to examine offender and victim
      characteristics, victim targeting and access, and modus operandi. Findings show
      that cases of sexual homicide and sexual murderers included in the current study
      differ in many aspects from the portrait of the sexual murderer and his or her
      crime depicted in previous studies. The authors' results may prove useful to the
      police officers responsible for the investigation of these crimes. 

PMID- 22871586
TI  - Predicting recidivism in adolescents with behavior problems using PCL-SV.
AB  - Studies show that identifying persistent delinquents on the basis of early
      antisocial conduct yields a significant error rate. However, evaluating childhood
      or adolescent psychopathic traits is likely to improve matters in this regard.
      This study seeks to verify the contribution of psychopathic traits in adolescence
      to antisocial conduct prediction in early adulthood. To this end, a French
      version of the Psychopathy Checklist -Screening Version (PCL-SV) adapted to
      adolescents is used to evaluate psychopathic traits in 27 youths aged 15 to 19
      years recruited in youth centres and presenting behavioral problems reaching a
      clinical threshold. The PCL-SV scores contribute significantly above and beyond
      indices of delinquent behavior to predict self-reported antisocial conduct 2
      years later and, specifically, to predict criminal versatility and violent
      recidivism. 

PMID- 22871588
TI  - Unexpected dominance: Brugada syndrome SCN5A variants exert negative dominance
      via alpha-subunit interaction.

PMID- 22871589
TI  - Monomeric C-reactive protein and inflammatory injury in myocardial infarction.

PMID- 22871590
TI  - Chemokine (C-C motif) receptor 2 mediates mast cell migration to abdominal aortic
      aneurysm lesions in mice.
AB  - AIMS: Mast cells participate importantly in abdominal aortic aneurysms (AAAs) by
      releasing inflammatory cytokines to promote vascular cell protease expression and
      arterial wall remodelling. Mast cells accumulate in AAA lesions during disease
      progression, but the exact chemokines by which mast cells migrate to the site of
      vascular inflammation remain unknown. This study tested the hypothesis that mast
      cells use chemokine (C-C motif) receptor 2 (CCR2) for their accumulation in
      experimental mouse AAA lesions. METHODS AND RESULTS: We generated mast cell and
      apolipoprotein E double-deficient (Apoe(-/-)Kit(W-sh/W-sh)) mice and found that
      they were protected from angiotensin II (Ang II) chronic infusion-induced AAAs
      compared with Apoe(-/-) littermates. Using bone-marrow derived mast cells (BMMC)
      from Apoe(-/-) mice and CCR2 double-deficient (Apoe(-/-)Ccr2(-/-)) mice, we
      demonstrated that Apoe(-/-)Kit(W-sh/W-sh) mice receiving BMMC from Apoe(-/-)Ccr2(
      /-) mice, but not those from Apoe(-/-) mice, remained protected from AAA
      formation. Adoptive transfer of BMMC from Apoe(-/-) mice into Apoe(-/-)Kit(W-sh/W
      sh) mice also increased lesion content of macrophages, T cells, and MHC class II
      positive cells; there was also increased apoptosis, angiogenesis, cell
      proliferation, elastin fragmentation, and medial smooth muscle cell loss. In
      contrast, adoptive transfer of BMMC from Apoe(-/-)Ccr2(-/-) mice into Apoe(-/
      )Kit(W-sh/W-sh) mice did not affect these variables. CONCLUSIONS: The increased
      AAA formation and associated lesion characteristics in Apoe(-/-)Kit(W-sh/W-sh)
      mice after receiving BMMC from Apoe(-/-) mice, but not from Apoe(-/-)Ccr2(-/-)
      mice, suggests that mast cells use CCR2 as the chemokine receptor for their
      recruitment in Ang II-induced mouse AAA lesions.

PMID- 22871591
TI  - MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in
      vivo.
AB  - AIMS: Medial artery calcification is a common macroangiopathy that initiates from
      a cell-regulated process similar to osteogenesis. Although the mechanisms
      governing this process remain unclear, epigenomic regulation by specific
      microRNAs might play a role in vascular smooth muscle cell (VSMC) calcification.
      In this study, we aimed to investigate whether miR-204 participates in the
      regulation of VSMC calcification. METHODS AND RESULTS: We found that miR-204 was
      suppressed in mouse aortic VSMCs during beta-glycerophosphate-induced
      calcification, whereas Runx2 protein levels were elevated. Overexpression of miR
      204 by transfection of miR-204 mimics decreased Runx2 protein levels and
      alleviated beta-glycerophosphate-induced osteoblastic differentiation of VSMCs,
      whereas miR-204 inhibition by transfection of miR-204 inhibitors significantly
      elevated Runx2 protein levels and enhanced osteoblastic differentiation of VSMCs,
      suggesting the role of miR-204 as an endogenous attenuator of Runx2 in VSMC
      calcification. Luciferase reporter assays revealed Runx2 as the direct target of
      miR-204 by overexpression of miR-204 on the wild-type or mutant 3'-UTR sequences
      of Runx2 in VSMCs. In vivo overexpression of miR-204 by injection of miR-204
      agomirs in Kunming mice attenuated vitamin D3-induced medial artery
      calcification. CONCLUSION: Our study has shown that down-regulation of miR-204
      may contribute to beta-glycerophosphate-induced VSMC calcification through
      regulating Runx2. miR-204 represents an important new regulator of VSMC
      calcification and a potential therapeutic target in medial artery calcification.

PMID- 22871593
TI  - Cell fate regulation in early mammalian development.
AB  - Preimplantation development in mammals encompasses a period from fertilization to
      implantation and results in formation of a blastocyst composed of three distinct
      cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives
      rise to the organism, while the trophectoderm and the primitive endoderm
      contribute to extraembryonic tissues that support embryo development after
      implantation. In many vertebrates, such as frog or fish, maternally supplied
      lineage determinants are partitioned within the egg. Cell cleavage that follows
      fertilization results in polarization of these factors between the individual
      blastomeres, which become restricted in their developmental fate. In contrast,
      the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage,
      individual blastomeres retain the potential to form all lineages. How are cell
      lineages specified in the absence of a maternally supplied blueprint? This is a
      fundamental question in the field of developmental biology. The answer to this
      question lies in understanding the cell-cell interactions and gene networks
      involved in embryonic development prior to implantation and using this knowledge
      to create testable models of the developmental processes that govern cell fates.
      We provide an overview of classic and contemporary models of early lineage
      development in the mouse and discuss the emerging body of work that highlights
      similarities and differences between blastocyst development in the mouse and
      other mammalian species.

PMID- 22871594
TI  - Research on human burden/toxicants.

PMID- 22871592
TI  - Deficiency of cathepsin S attenuates angiotensin II-induced abdominal aortic
      aneurysm formation in apolipoprotein E-deficient mice.
AB  - AIMS: Abdominal aortic aneurysm (AAA) is characterized by extensive aortic wall
      matrix degradation that contributes to the remodelling and eventual rupture of
      the arterial wall. Elastinolytic cathepsin S (Cat S) is highly expressed in human
      aneurysmal lesions, but whether it contributes to the pathogenesis of AAA remains
      unknown. METHODS AND RESULTS: AAAs were induced in apolipoprotein E (ApoE) and
      Cat S compound mutant (Apoe(-/-)Ctss(-/-)) mice and in ApoE-deficient Cat S wild
      type littermates (Apoe(-/-)Ctss(+/+)) by chronic angiotensin II infusion, and AAA
      lesions were analysed after 28 days. We found that Cat S expression increased
      significantly in mouse AAA lesions. The AAA incidence in Apoe(-/-)Ctss(-/-) mice
      was much lower than that in Apoe(-/-)Ctss(+/+) mice (10 vs. 80%). Cat S
      deficiency significantly reduced external and luminal abdominal aortic diameters,
      medial elastin fragmentation, and adventitia collagen content. Cat S deficiency
      reduced aortic lesion expression and the activity of matrix metalloproteinase
      (MMP)-2, MMP-9, and Cat K, but not the activity of other major cathepsins, such
      as Cat B and Cat L. Absence of Cat S significantly reduced AAA lesion media
      smooth muscle cell (SMC) apoptosis, lesion adventitia microvessel content, and
      inflammatory cell accumulation and proliferation. In vitro studies proved that
      Cat S helps promote SMC apoptosis, angiogenesis, monocyte and T-cell
      transmigration, and T-cell proliferation--all of which are essential to AAA
      pathogenesis. CONCLUSIONS: These data provide direct evidence that Cat S plays an
      important role in AAA formation and suggest that Cat S is a new therapeutic
      target for human AAA.

PMID- 22871595
TI  - Major food safety episodes in Taiwan: implications for the necessity of
      international collaboration on safety assessment and management.
AB  - The major food safety episodes that occurred in Taiwan during the past decade are
      briefly reviewed in this paper. Among the nine major episodes surveyed, with the
      exception of a U.S. beef (associated with Creutzfeldt-Jakob disease)-related
      incident, all the others were associated with chemical toxicants. The general
      public, which has a layperson attitude of zero tolerance toward food safety, may
      panic over these food-safety-associated incidents. However, the health effects
      and impacts of most incidents, with the exception of the melamine incident, were
      essentially not fully evaluated. The mass media play an important role in
      determining whether a food safety concern becomes a major incident. A well
      coordinated and harmonized system for domestic and international collaboration to
      set up standards and regulations is critical, as observed in the incidents of
      pork with ractopamine, Chinese hairy crab with nitrofuran antibiotics, and U.S.
      wheat with malathion. In the future, it can be anticipated that food safety
      issues will draw more attention from the general public. For unknown new
      toxicants or illicit adulteration of food, the establishment of a more proactive
      safety assessment system to monitor potential threats and provide real-time
      information exchange is imperative.

PMID- 22871596
TI  - Plasticizer incident and its health effects in Taiwan.
AB  - The May 23, 2011, plasticizer incident was one of the most serious food safety
      issues that ever occurred in Taiwan. Most, if not all, plasticizer-contaminated
      food items were due to malicious replacement of palm oil with phthalate
      plasticizer(s) in the cloudy-agent formulas by two upstream manufacturers. The
      incumbent agencies in Taiwan took necessary actions to minimize the harm caused
      by the incident and to ease the panic of the general public. In this paper, the
      incident was briefly reviewed and the situations of phthalate exposure in general
      public and pregnant women were assessed. Subsequently, the associations between
      phthalates exposure and the adverse health effects, such as shortened anogenital
      distance in baby boys, premature thelarche in young girls, endometriosis,
      adenomyosis, and leiomyoma in women, and decreased semen quality in men, were
      discussed. Food safety issue has become a worldwide concern and early detection
      of potential new toxicants in the foods is indispensable. Therefore, it is
      imperative to establish an international network for early warning or sentinel on
      food safety.

PMID- 22871597
TI  - Possible mechanism of phthalates-induced tumorigenesis.
AB  - Phthalates--substances used in the manufacture of plastics--are considered as
      possible human carcinogens and tumor-promoting agents. The worldwide annual
      production of plastics surpassed 300 million tons in 2010. Plastics are an
      indispensable material in modern society, and many products manufactured from
      plastics are a boon to public health; however, plastics also pose health risks.
      Animal studies have indicated that phthalates are carcinogenic, but human
      epidemiological data confirming this carcinogenicity in humans are limited. The
      activation of peroxisome proliferator-activated receptor alpha (PPARalpha), which
      has been observed in rodent carcinogenesis, has not been observed in humans.
      Here, we review the hypothesis that the aryl hydrocarbon receptor (AhR) and its
      downstream signaling cascade promote phthalate-induced tumorigenesis.

PMID- 22871598
TI  - The association between phthalate exposure and asthma.
AB  - Asthma is a chronic inflammatory disorder of the airway, characterized by airway
      hyperresponsiveness. It is a disabling disease with an increasing prevalence,
      resulting in heavy social and economic burdens worldwide. Humans are extensively
      exposed to phthalates, and many epidemiological studies have shown a relationship
      between phthalate exposure and asthma in recent decades. Earlier experimental
      studies focused on inflammatory cells, demonstrating the adjuvant effects,
      immunomodulatory effects, or immunosuppressive effects related to phthalate
      exposure. Recent studies have shown that phthalates may have a direct effect on
      airway epithelial cells and contribute to airway remodeling, which is the
      cardinal pathologic characteristic of chronic asthma, with a high correlation
      with disease severity. Through these efforts, phthalates have been recognized as
      important environmental factors in the pathogenesis of asthma, but further
      studies are still required to elucidate the detailed mechanism. This review
      discusses the current status of human exposure to phthalates in Taiwan and
      summarizes the epidemiological and experimental evidence related to the roles of
      phthalate exposure in the development of asthma and associated diseases.

PMID- 22871599
TI  - International Conference on Food and Drug Safety Assessment. Editorial.

PMID- 22871600
TI  - Immunomodulatory effects of environmental endocrine disrupting chemicals.
AB  - During recent decades more than 100,000 new chemicals have been introduced as
      common consumer products into our environment. Among these chemicals, endocrine
      disrupting chemicals (EDCs) are of particular concern owing to their toxicity in
      animal studies and their impacts on human health. EDCs are ubiquitous in the
      environment, including the air, water, and soil. The endocrine-disrupting effect
      of EDCs has been found to imitate the action of steroid hormones and promote
      several endocrine and reproductive disorders in both animal and human studies. In
      the present review, we focus on the effects of EDCs on the immune system. EDCs
      interfere with the synthesis of cytokines, immunoglobulins, and inflammatory
      mediators, and they also affect the activation and survival of immune cells. The
      dysfunction of the immune system caused by EDCs may lead to the attenuation of
      immunity (immunodeficiency) against infection or hyperreactivity of immune
      responses (allergy and autoimmune disease). In this review, we summarize
      epidemiologic, animal, and cell studies to demonstrate the potential effects of
      EDCs on immunity, allergy, and autoimmune diseases. We also address the impact of
      EDCs on epigenetic regulation.

PMID- 22871601
TI  - Alkylphenols--potential modulators of the allergic response.
AB  - The prevalence of allergic diseases has increased in recent decades. Allergic
      diseases, particularly asthma, are complex diseases with strong gene-environment
      interactions. Epidemiological studies have identified a variety of risk factors
      for the development of allergic diseases. Among them, endocrine-disrupting
      chemicals (EDCs) play an important role in triggering or exacerbating these
      diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have
      been recognized as common toxic and xenobiotic endocrine disrupters. Due to their
      low solubility, high hydrophobicity, and low estrogenic activity, they tend to
      accumulate in the human body and may be associated with the adverse effects of
      allergic diseases. Recently, new evidence has supported the importance of
      alkylphenols in the in vitro allergic response. This review focuses on the
      effects of alkylphenols on several key cell types in the context of allergic
      inflammation.

PMID- 22871602
TI  - Yusho: 43 years later.
AB  - The aim of the present study is to describe recent issues with Yusho disease in
      Japan, describe the state of dioxin accumulation and the intake of dioxin via
      food in Japan, and introduce the Japan Environment and Children's Study. Yusho
      disease manifested in western Japan in 1968. The causes of Yusho are believed to
      be dioxin-related compounds, mainly polychlorinated biphenyls (PCBs) and
      polychlorinated dibenzofurans (PCDFs), via the ingestion of rice oil produced in
      February 1968. As of March 31, 2011, there were 1961 registered Yusho cases, but
      of these 539 are deceased. A retrospective cohort study on registered Yusho cases
      reported that the standardized mortality ratios (SMRs) for the major causes of
      death were not significantly elevated, with the exception of all-cancer
      (SMR=1.26; 95% confidence interval [CI]: 1.03-1.53) and lung cancer mortality
      (SMR=1.56; 95% CI: 1.03-2.27) in males. The results of the Yusho mortality study
      show that the SMR for liver cancer in males tends to decrease over time. In 2011,
      the Ministry of the Environment of Japan reported that the average concentration
      of dioxins in the blood (2002-2010) of the Japanese people was 19 pg-TEQ/g-fat,
      demonstrating a range of 0.10-130 pg-TEQ/g-fat, and that the average dioxin
      intake from food (2002-2010) was 0.82 pg-TEQ/kg-body weight/day, demonstrating a
      range of 0.031-6.2 pg-TEQ/kg-body weight/day according to 2006 WHO TEFs. The
      Japan Environment and Children's Study Project was launched in 2011 and is
      supported by the Ministry of the Environment of Japan. In this project, 100,000
      mother and child pairs will be recruited over 3 years from designated study
      areas. Follow-up examinations will be carried out from pregnancy until the
      children are 13 years of age (a so-called birth-cohort study). This project will
      be implemented by the National Center at the National Institute for Environmental
      Studies and is supported by the Medical Support Center at the National Center for
      Child Health and Development. Field operations will be performed at 15 designated
      regional centers nationwide.

PMID- 22871603
TI  - Impact of regulatory science on global public health.
AB  - Regulatory science plays a vital role in protecting and promoting global public
      health by providing the scientific basis for ensuring that food and medical
      products are safe, properly labeled, and effective. Regulatory science research
      was first developed for the determination of product safety in the early part of
      the 20th Century, and continues to support innovation of the processes needed for
      regulatory policy decisions. Historically, public health laws and regulations
      were enacted following public health tragedies, and often the research tools and
      techniques required to execute these laws lagged behind the public health needs.
      Throughout history, similar public health problems relating to food and
      pharmaceutical products have occurred in countries around the world, and have
      usually led to the development of equivalent solutions. For example, most
      countries require a demonstration of pharmaceutical safety and efficacy prior to
      marketing these products using approaches that are similar to those initiated in
      the United States. The globalization of food and medical products has created a
      shift in regulatory compliance such that gaps in food and medical product safety
      can generate international problems. Improvements in regulatory research can
      advance the regulatory paradigm toward a more preventative, proactive framework.
      These improvements will advance at a greater pace with international
      collaboration by providing additional resources and new perspectives for
      approaching and anticipating public health problems. The following is a review of
      how past public health disasters have shaped the current regulatory landscape,
      and where innovation can facilitate the shift from reactive policies to proactive
      policies.

PMID- 22871604
TI  - Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te-based
      quantum dot 705 toxicity in vivo.
AB  - The safety of quantum dots (QDs) 705 was evaluated in this study. Mice were
      treated with QD705 (intravenous) at a single dose of (40 pmol) for 4, 12, 16, and
      24 weeks. Effects of QD705 on kidneys were examined. While there was a lack of
      histopathology, reduction in renal functions was detected at 16 weeks. Electron
      microscopic examination revealed alterations in proximal convoluted tubule (PCT)
      cell mitochondria at even much earlier time, including disorientation and
      reduction of mitochondrial number (early change), mitochondrial swelling, and
      later compensatory mitochondrial hypertrophy (enlargement mitochondria: giant
      mitochondria with hyperplastic inner cristae) as well as mitochondrial
      hyperplasia (increase in mitochondrial biogenesis and numbers) were observed.
      Such changes probably represent compensatory attempts of the mitochondria for
      functional loss or reduction of mitochondria in QD705 treated animals. Moreover,
      degeneration of mitochondria (myelin-figure and cytoplasmic membranous body
      formation) and degradation of cytoplasmic materials (isolated cytoplasmic pockets
      of degenerated materials and focal cytoplasmic degradation) also occurred in
      later time points (16-24 weeks). Such mitochondrial changes were not identical
      with those induced by pure cadmium. Taken together, we suggest that mitochondria
      appeared to be the target of QD705 toxicity and specific mitochondrial markers
      may be useful parameters for toxicity assessments of QDs or other metal-based
      nanomaterials.

PMID- 22871605
TI  - Lower limb muscle moments and power during recovery from forward loss of balance
      in male and female single and multiple steppers.
AB  - BACKGROUND: Studying recovery responses to loss of balance may help to explain
      why older adults are susceptible to falls. The purpose of the present study was
      to assess whether male and female older adults, that use a single or multiple
      step recovery strategy, differ in the proportion of lower limb strength used and
      power produced during the stepping phase of balance recovery. METHODS: Eighty
      four community-dwelling older adults (47 men, 37 women) participated in the
      study. Isometric strength of the ankle, knee and hip joint flexors and extensors
      was assessed using a dynamometer. Loss of balance was induced by releasing
      participants from a static forward lean (4 trials at each of 3 forward lean
      angles). Participants were instructed to recover with a single step and were
      subsequently classified as using a single or multiple step recovery strategy for
      each trial. FINDINGS: (1) Females were weaker than males and the proportion of
      females that were able to recover with a single step were lower than for males at
      each lean magnitude. (2) Multiple compared to single steppers used a
      significantly higher proportion of their hip extension strength and produced less
      knee and ankle joint peak power during stepping, at the intermediate lean angle.
      INTERPRETATION: Strength deficits in female compared to male participants may
      explain why a lower proportion of female participants were able to recover with a
      single step. The inability to generate sufficient power in the stepping limb
      appears to be a limiting factor in single step recovery from forward loss of
      balance.

PMID- 22871606
TI  - Markers of pathological excitability derived from principal dynamic modes of
      hippocampal neurons.
AB  - Transformation of principal dynamic modes (PDMs) under epileptogenic conditions
      was investigated by computing the Volterra kernels in a rodent epilepsy model
      derived from a mouse whole hippocampal preparation, where epileptogenesis was
      induced by altering the concentrations of Mg(2 +) and K(+) of the perfusate for
      different levels of excitability. Both integrating and differentiating PDMs were
      present in the neuronal dynamics, and both of them increased in absolute
      magnitude for increased excitability levels. However, the integrating PDMs
      dominated at all levels of excitability in terms of their relative contributions
      to the overall response, whereas the dominant frequency responses of the
      differentiating PDMs were shifted to higher ranges under epileptogenic
      conditions, from ripple activities (75-200 Hz) to fast ripple activities (200-500
      Hz).

PMID- 22871607
TI  - Comparative effects of in ovo exposure to sodium perchlorate on development,
      growth, metabolism, and thyroid function in the common snapping turtle (Chelydra
      serpentina) and red-eared slider (Trachemys scripta elegans).
AB  - Perchlorate is a surface and groundwater contaminant found in areas associated
      with munitions and rocket manufacturing and use. It is a thyroid-inhibiting
      compound, preventing uptake of iodide by the thyroid gland, ultimately reducing
      thyroid hormone production. As thyroid hormones influence metabolism, growth, and
      development, perchlorate exposure during the embryonic period may impact
      embryonic traits that ultimately influence hatchling performance. We topically
      exposed eggs of red-eared sliders (Trachemys scripta) and snapping turtles
      (Chelydra serpentina) to 200 and 177 MUg/g of perchlorate (as NaClO(4)),
      respectively, to determine impacts on glandular thyroxine concentrations,
      embryonic growth and development, and metabolic rates of hatchlings for a period
      of 2 months post-hatching. In red-eared sliders, in ovo perchlorate exposure
      delayed hatching, increased external yolk size at hatching, increased hatchling
      mortality, and reduced total glandular thyroxine concentrations in hatchlings. In
      snapping turtles, hatching success and standard metabolic rates were reduced,
      liver and thyroid sizes were increased, and total glandular thyroxine
      concentrations in hatchlings were reduced after exposure to perchlorate. While
      both species were negatively affected by exposure, impacts on red-eared sliders
      were most severe, suggesting that the slider may be a more sensitive sentinel
      species for studying effects of perchlorate exposure to turtles.

PMID- 22871608
TI  - Endocrine disruption caused by oral administration of atrazine in European quail
      (Coturnix coturnix coturnix).
AB  - The widely used herbicide atrazine (ATZ) has been reported to exhibit
      reproductive toxicity in rats, fish and amphibians, with an avian LD(50) of 5000
      mg/kg. In the present work, ATZ was administered as a single oral dose of 25 or
      100 mg/kg to female European quail (Coturnix coturnix coturnix) at days 0, 5 and
      10 of the experiment, being the animals sampled at days 15, 30 and 45. ATZ
      significantly increased the expression of hepatic estrogen receptor alpha
      (ERalpha) at both doses at day 30. An important increase was also observed in
      plasma 17beta-estradiol (E2) concentrations. ATZ at 100 mg/kg increased the
      circulating concentration of vitellogenin (Vtg), but this effect was not related
      with an increase in hepatic Vtg mRNA levels. ATZ had no effect on the hepatic
      expression of both cytochrome P450 1A4 (CYP1A4) or the related biotransformation
      activity ethoxyresorufin-O-deethylase (EROD). These results led to the conclusion
      that ATZ provokes an estrogenic effect in sexually mature females of European
      quail. Further studies are necessary to establish the effect on sexual
      development or reproduction of female and male birds in the wild.

PMID- 22871610
TI  - Nucleolar localization of a netrin-1 isoform enhances tumor cell proliferation.
AB  - Netrin-1 displays proto-oncogenic activity in several cancers, which is thought
      to be due to the ability of this secreted cue to stimulate survival when bound to
      its receptors. We showed that in contrast to full-length, secreted netrin-1, some
      cancer cells produced a truncated intranuclear form of netrin-1 (DeltaN-netrin-1)
      through an alternative internal promoter. Because of a nucleolar localization
      signal located in its carboxyl terminus, DeltaN-netrin-1 was targeted to the
      nucleolus, where it interacted with nucleolar proteins, affected nucleolar
      ultrastructure, and interacted with the promoters of ribosomal genes. Moreover,
      DeltaN-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo.
      Thus, some cancer cells produce not only a full-length, secreted form of netrin-1
      that promotes cell survival but also a truncated netrin-1 that stimulates cell
      proliferation, potentially by enhancing ribosome biogenesis.

PMID- 22871611
TI  - The abluminal endothelial membrane in neurovascular remodeling in health and
      disease.
AB  - After brain injury, blood-brain barrier (BBB) integrity can be compromised as a
      consequence of the breakdown of cell-cell interactions in the neurovascular unit,
      resulting in the loss of the characteristic endothelial luminal-to-abluminal
      structure. During the process of restoration of the BBB and vascularization, the
      endothelial cells are continuously reshaped, with both the luminal and abluminal
      membranes serving as sites of signaling. Here, we focus on the bidirectional
      signaling processes that are rapidly initiated between endothelial and
      perivascular cells and occur in certain brain diseases or in response to injury.
      The goal of these processes is (i) the reemergence of endothelial cell polarity,
      (ii) the remodeling of extracellular matrix interactions, (iii) the realignment
      of pericytes and astrocytic endfeet with endothelial cells, and (iv) the
      restitution of a well-organized and stable BBB. This abluminal membrane
      exemplifies how the brain vasculature responds to stressors and may represent
      promising targets for therapeutic interventions of brain diseases.

PMID- 22871609
TI  - Microtubules underlie dysfunction in duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal X-linked degenerative muscle disease
      caused by the absence of the microtubule-associated protein dystrophin, which
      results in a disorganized and denser microtubule cytoskeleton. In addition,
      mechanotransduction-dependent activation of calcium (Ca(2+)) and reactive oxygen
      species (ROS) signaling underpins muscle degeneration in DMD. We show that in
      muscle from adult mdx mice, a model of DMD, a brief physiologic stretch elicited
      microtubule-dependent activation of NADPH (reduced-form nicotinamide adenine
      dinucleotide phosphate) oxidase-dependent production of ROS, termed X-ROS.
      Further, X-ROS amplified Ca(2+) influx through stretch-activated channels in mdx
      muscle. Consistent with the importance of the microtubules to the dysfunction in
      mdx muscle, muscle cells with dense microtubule structure, such as those from
      adult mdx mice or from young wild-type mice treated with Taxol, showed increased
      X-ROS production and Ca(2+) influx, whereas cells with a less dense microtubule
      network, such as young mdx or adult mdx muscle treated with colchicine or
      nocodazole, showed little ROS production or Ca(2+) influx. In vivo treatments
      that disrupted the microtubule network or inhibited NADPH oxidase 2 reduced
      contraction-induced injury in adult mdx mice. Furthermore, transcriptome analysis
      identified increased expression of X-ROS-related genes in human DMD skeletal
      muscle. Together, these data show that microtubules are the proximate element
      responsible for the dysfunction in Ca(2+) and ROS signaling in DMD and could be
      effective therapeutic targets for intervention.

PMID- 22871612
TI  - The investigation of Cushing syndrome: essentials in optimizing appropriate
      diagnosis and management.
AB  - The investigation of Cushing syndrome (CS) should start with careful history
      taking and clinical examination, and exogenous steroid usage must be excluded. It
      is essential to confirm hypercortisolism before further investigations are
      undertaken. The recommended first-line tests include midnight salivary cortisol
      and/or the 1 mg overnight or low-dose dexamethasone suppression tests. The next
      step is to differentiate adrenocorticotrophin (ACTH)-dependent from ACTH
      independent CS by measuring ACTH. With ACTH-dependence, further investigations
      should differentiate pituitary-dependent from ectopic ACTH-dependent CS. Many
      dynamic tests may be considered, but we suggest that bilateral inferior petrosal
      sinus sampling should be performed in almost all patients with ACTH-dependent CS,
      except for patients with a pituitary macroadenoma. Imaging should include MR
      scanning of the pituitary, and CT scanning of the chest and abdomen to look for
      an ectopic source. Confirmation of the diagnosis of CS and accurate localization
      of its source are vital to optimize therapy for this complex disorder.

PMID- 22871613
TI  - Prevalence of attention deficit hyperactivity symptoms in female schoolchildren
      in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is the
      most commonly seen developmental disorder, with significant impacts on the
      child's social, psychological, and scholastic functioning. The aim of this study
      was to determine the prevalence and sociodemographic correlates of ADHD in female
      primary schoolchildren. DESIGN AND SETTING: A cross-sectional study conducted in
      Al-Khobar Town, Eastern Saudi Arabia. METHODS: A random sample of six primary
      schools for girls was chosen, from which samples of 1009 students were selected
      by systematic random sampling, with ages ranging between 6 and 15 years (mean and
      standard deviation, 9.2 [1.9]). All subjects were screened for different types of
      ADHD using the Attention Deficit Disorders Evaluation Scale. RESULTS: The overall
      prevalence of ADHD was 3.5%. The prevalence of children with ADHD/inattentive
      type was 2.1% and the prevalence of children with ADHD/hyperactive-impulsive type
      was 5.6%. This rate decreased significantly with increase in age. The prevalence
      was higher in government school students, among Saudi citizens, later born
      siblings, higher number of siblings, and lower parental education. CONCLUSIONS:
      It was concluded that the prevalence of ADHD in female primary schoolchildren is
      comparable with what has been reported in other studies. Some demographic factors
      should be taken into consideration when interpreting this result. Implications
      and recommendations to the concerned authorities are outlined to improve the
      health and educational care services to help these children.

PMID- 22871614
TI  - Correlation between plasma N-terminal pro-brain natriuretic peptide levels and
      changes in New York Heart Association functional class, left atrial size, left
      ventricular size and function after mitral and/or aortic valve replacement.
AB  - BACKGROUND AND OBJECTIVES: Elevated plasma brain natriuretic peptide (BNP) levels
      have been demonstrated in patients with chronic valvular disease. We designed the
      present study to assess whether changes in N-terminal pro-brain natriuretic
      peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic
      valve replacement reflect changes in heart failure (HF) symptoms including New
      York Heart Association (NYHA) class and changes in left atrium (LA) size, left
      ventricle (LV) size and LV function. DESIGN AND SETTING: A prospective
      observational nonrandomized study among consecutive patients undergoing mitral
      and/or aortic valve replacement in our center. PATIENTS AND METHODS: The study
      population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were
      males) who underwent surgical mitral valve replacement (12 patients), aortic
      valve replacement (8 patients) and combined mitral and aortic valve replacement
      (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA
      class assessments were performed before and 6 months after surgery. RESULTS: The
      decrease in NT-proBNP was associated with decrease in left atrial dimension (r =
      0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic
      dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001)
      after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was
      associated with improvement in NYHA class. CONCLUSIONS: NT-proBNP levels after
      mitral, aortic and double valve replacement correlates with changes in HF
      manifestations as well as changes in LA size and LV dimension and function. Thus,
      we hypothesize that interval measurement of the NT-proBNP level at clinic visits
      can allow early detection of any clinical deterioration as well as the
      possibility of assessment of the long-term outcome of those patients.

PMID- 22871615
TI  - Vitamin D insufficiency and deficiency in children with chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Hypovitaminosis D is a frequent condition in normal
      populations. Children with chronic kidney disease (CKD) present a high risk of
      developing complications due to hypovitaminosis D. Our aim was to determine the
      frequency of vitamin D insufficiency/deficiency in children with different stages
      of CKD who were followed up at King Abdulaziz University Hospital (KAUH), Jeddah,
      Saudi Arabia. DESIGN AND SETTING: University hospital-based case-control study of
      children followed up between March 2010 and March 2011. PATIENTS AND METHODS:
      Blood was extracted from children with CKD to measure urea, creatinine,
      hemoglobin, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone
      (iPTH), and vitamin D3 levels. We calculated correlations between iPTH and
      vitamin D levels, and associations between vitamin D levels and CKD stages.
      RESULTS: The frequency of vitamin D insufficiency/deficiency was high among the
      cases and controls. Children with CKD had significantly lower levels of vitamin D
      than their peers with normal kidney function (P=.05) with a mean (SD) level of
      17.5 (9.9) ng/mL versus 21.0 (13.4) ng/mL for the control group. Among the
      children with CKD, 36 (45.0%) had vitamin D insufficiency, 24 (30.0%) had vitamin
      D deficiency, and 10 (12.5%) had severe deficiency. There was a positive
      correlation between vitamin D3 level and CKD stages (Kendall tau=0.22, P=.003). A
      significant association existed between glomerular filtration rate and vitamin D3
      deficiency (P=.002). There was a significant negative correlation between iPTH
      and vitamin D3 concentrations (Spearman correlation coefficient= -0.27, P=.01). A
      significant association existed between age and vitamin D3 level (P < .0001).
      CONCLUSION: Vitamin D insufficiency/deficiency is more frequent in children with
      CKD than in those with normal kidney function.

PMID- 22871616
TI  - T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma
      in a Saudi Arabian population: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: Genetic association studies have demonstrated that
      over 100 variants in target genes (including ADAM33) are associated with airway
      remodeling and hyper-responsiveness in different ethnic groups; however, this has
      never been evaluated in Arabic populations. The objective of this study was to
      determine whether ADAM33 polymorphisms that are associated with asthma in a
      population of asthmatic children from Saudi Arabia. DESIGN AND SETTING: A cross
      sectional pilot study comparing the polymorphisms of normal subjects and
      asthmatic patients from Saudi Arabia over a period of 1 year. PATIENTS AND
      METHODS: One hundred and seven Saudi asthmatic children and 87 healthy Saudi
      children of 3-12 years old were assessed for allelic association of ADAM33 T1
      (rs2280091), T2 (rs2280090), ST+4 (rs44707) and S1 (rs3918396) SNPs to asthma.
      Genotyping was done by real-time PCR, multiplex ARMS and PCR-RFLP. RESULTS: T1
      and T2 SNP genotype frequencies in asthmatic children were significantly
      different compared to controls (P < .05), indicating allelic association with
      asthma. The T1 A/G and G/G and the T2 A/G and A/A genotypes (P=.0013 and P=.008,
      respectively) but not S1 and ST+4, increased the risk of asthma when using the
      best fit dominant model. Strong linkage disequilibrium between T1 (rs2280091) and
      T2 (rs2280090) was observed (r2=0.83; D'=0.95; P < .001). The haplotype G-A-A-C
      was significantly more frequent in asthmatics, thus supporting the association of
      T1 G-allele and T2 A-allele with increased predisposition to asthma (P=.007).
      CONCLUSIONS: T1 A/G and T2 G/A ADAM33 polymorphisms, but not S1 or ST+4, were
      significantly associated with asthma development in Saudi children, like those
      reported for white and Hispanic populations in the United States.

PMID- 22871617
TI  - Prevalence of Xmnl Ggamma polymorphism in Egyptian patients with beta-thalassemia
      major.
AB  - BACKGROUND AND OBJECTIVES: beta-thalassemia results from a deficiency of beta
      globin chains leading to an excess in a globin chains resulting in hypochromic
      microcytic red cells, ineffective erythropoiesis and hemolytic anemia. It is a
      result of a decline of HbF synthesis during the first year of life. F-cell levels
      are influenced by a sequence variant (C->T) at position -158 upstream of the 
      globin gene, so the frequency of the Xmnl Ggamma polymorphism in Egyptian
      patients with b-thalassemia major needed evaluation to decide on the value of HbF
      augmentation drugs in treating Egyptian b-thalessemia. DESIGN AND SETTING: A
      cross-sectional study including 30 beta-thalassemia major patients diagnosed and
      attending the Pediatric Hematology Unit, Children's University Hospital, Ain
      Shams University, Cairo, Egypt, in the period from October 2008 to October 2009.
      PATIENTS AND METHODS: The 17 males and 13 females underwent a medical history and
      physical examination. Tests included a complete blood count, hemoglobin
      electrophoresis, serum ferritin, and detection of Xmnl Ggamma polymorphism by
      PCR. RESULTS: The mean (SD) age was [2]10.2 (6.9) years. The most frequent
      genotype observed was homozygosity for the absence of the site Xmnl (-/-) in 96%
      of cases. Heterozygosity (+/-) genotype was detected in 4% of cases, while
      homozygosity for the site XmnI (+/+) genotype was absent. Genotype was not
      related to age at first transfusion, fetal hemoglobin level or transfusion
      frequency. CONCLUSION: Despite the small sample size, the study demonstrated that
      Egyptian beta-thalessemia patients have low frequency of positivity for the Xmnl
      polymorphism whether in heterozygous (+/-) or homozygous (+/+) state.

PMID- 22871618
TI  - The outcome of pharmacist counseling at the time of hospital discharge: an
      observational nonrandomized study.
AB  - BACKGROUND AND OBJECTIVES: Adverse drug events (ADEs) may occur after discharge
      from acute care hospitalization because of limited instruction on medications at
      discharge. The right instructions given to patients may reduce the risk of ADEs.
      The objective of our study was to assess a program involving comprehensive
      medication counseling provided by pharmacists at the time of discharge from a
      tertiary hospital in Riyadh, Saudi Arabia. DESIGN AND SETTING: A prospective,
      nonrandomized observational study over a period of 3 months in a 1000-bed
      tertiary hospital. PATIENTS AND METHODS: Patients discharged from the internal
      medicine wards with more than three medications received comprehensive pharmacist
      counseling. The intervention pharmacist counseled patients about their discharge
      medications and provided written materials as needed. Topics discussed with the
      patients included the importance of following prescribed medication regimens and
      the indications, directions, and any potential side effects of discharge
      medications. The control group included similar patients who received routine
      discharge counseling by nurses. Two weeks after discharge, the same pharmacist
      called the patients and assessed the frequency of ADEs. Two independent
      clinicians reviewed each ADEs and judged its severity and preventability.
      RESULTS: Out of 200 patients included in the study (100 patients from the
      intervention group and 100 patients from the control group), 175 patients (87.5%)
      were successfully contacted two weeks after discharge (88 patients from the
      intervention group and 87 patients from the control group). ADEs occurred in 2
      patients (2.3%) in the intervention group and in 21 patients (24%; 23 incidents
      in 21 patients) in the control group (P < .001). In the control group, 14 ADEs
      (61%) were judged as preventable, and 9 (39%) were judged as serious.
      CONCLUSIONS: A comprehensive medication counseling program at hospital discharge
      reduced the incidence of ADEs two weeks after discharge from a tertiary hospital
      in Riyadh, Saudi Arabia. Further studies assessing the long-term outcomes of such
      a program are needed.

PMID- 22871620
TI  - The role of seating position in determining the injury pattern among unrestrained
      children involved in motor vehicle collisions presenting to a level I trauma
      center.
AB  - BACKGROUND AND OBJECTIVES: Seating position in motor vehicle collisions (MVC)
      plays a major role in determining the injury pattern in mainly restrained
      children. However, compliance with child seating and restraint laws is still
      suboptimal. The role of seating position in predicting injury patterns among
      unrestrained children has not been previously studied. DESIGN AND SETTING:
      Retrospective review based on the trauma registry of a level I trauma center in
      Riyadh, Saudi Arabia. Data collection was restricted to unrestrained children
      involved in MVC. PATIENTS AND METHODS: Between July 2001 and March 2010, 274
      records were identified. Detailed information about the collision, child seating
      position and the use of restraints was cross-verified using parental phone
      interviews. RESULTS: Of the 274 identified records, cross-verification was
      possible for 89 (32.4%) unrestrained children, 64 boys and 25 girls, with a mean
      (SD) age of 83 (40) months. Of these children, 41 (46.1%) were front seated (FS),
      and 48 (53.9%) were back seated (BS). There were higher rates of rollover (52.1%
      vs 24.4%, P=.02), ejection (41.7% vs 22%, P=.05), and occupant death ratio (14.8
      vs 4, P=.04) among BS children. However, the two groups did not differ in
      pediatric trauma scores, Glascow coma scale score, or age distribution. FS
      children were more likely to present with isolated head, neck or facial injuries
      (HNFI) (51.2% vs 25%, P=.01), whereas BS children were more likely to suffer long
      bone or pelvic fractures (LPF) (60.4% vs 36.6%, P=.025). CONCLUSION: Injury
      pattern can vary according to seating position among unrestrained children
      presenting at trauma centers after MVC. While FS children are more likely to
      present with HNFI, BS children more often sustain LPF. BS children had similar
      trauma severity compared with FS children despite the higher-impact nature of
      their MVCs. While highlighting the value of proper restraints use and seating
      position, these results can be valuable in the initial assessment of traumatized
      children involved in MVC.

PMID- 22871619
TI  - Trauma profile at a tertiary intensive care unit in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Trauma is a leading cause of death worldwide and in
      Saudi Arabia. This study describes the injury profiles and ICU outcomes of
      patients in a tertiary trauma care referral center in Riyadh, Saudi Arabia.
      DESIGN AND SETTING: A retrospective analysis of ICU data collected prospectively
      over 5 years in a 21-bed medical and surgical intensive care unit (ICU) in a
      tertiary care teaching hospital. PATIENTS AND METHODS: We collected ICU data on
      all patients admitted secondary to motor vehicle accidents (MVAs), excluding
      patients younger than 18 years, brain dead patients and readmissions. We
      collected data on age, gender, and Glasgow coma scale score at admission, injury
      severity scores, Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score, and other data. Multivariate logistic regression was used to identify
      predictors of mortality. RESULTS: During the study period, of 1659 patients, MVA
      was the most common cause of injury (78.4%), followed by pedestrian accident
      (12.7%). ICU mortality included 221 patients (13.3%) during the study period.
      Severe head injury, age > 60 years, Glascow coma scale score, injury severity
      scores, APACHE II and international normalized ratio were independent predictors
      of mortality. CONCLUSION: MVA is very common in our country and leads to
      significant mortality and morbidity. Public education and strict law enforcement
      are needed to reduce these adverse events.

PMID- 22871621
TI  - Methicillin-resistant Staphylococcus aureus in the western region of Saudi
      Arabia: prevalence and antibiotic susceptibility pattern.
AB  - BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA)
      emerged in 1960 and was a problem confined largely to the healthcare setting, or
      hospital-associated MRSA (HA-MRSA). In the 1990s, community-associated MRSA (CA
      MRSA) infections appeared. In Saudi Arabia, the prevalence of MRSA has increased
      in the past ten years and severe community-acquired infection has been reported.
      Our objective was to investigate the prevalence of MRSA and their antibiotic
      susceptibilities in the western region of Saudi Arabia. DESIGN AND SETTING: A
      retrospective review of the medical records of 186 S aureus infected patients
      diagnosed from November 2009 through October 2010. METHODS: S aureus was
      Identified based on Gram stain, catalase and coagulase tests. Susceptibility
      testing was performed using antibiotic discs and the VITEK 2 system. RESULTS:
      MRSA was isolated in 39.5% of the specimens. The isolates were commonly
      associated with wound, skin, and soft tissue infections (87.3%). The prevalence
      of MRSA was highest among patients who were 56 years old or older (52.2%). CA
      MRSA infections represented 31.5% of community S aureus infections, while HA-MRSA
      accounted 52.6% of hospital S aureus (P=.0029). All MRSA isolates in our study
      were susceptible to vancomycin, linozolid and teicoplanin. However, multi
      resistance was observed in 29.1% of the isolates and was significantly higher
      among HA-MRSA (P=.03). CONCLUSIONS: The prevalence of MRSA was 39.5%, and
      infection was commonly associated with wound, skin, and soft tissue infections.
      MRSA was more prevalent in hospitals and among older patients. All MRSA
      susceptible to vancomycin, linozolid and teicoplanin.

PMID- 22871622
TI  - Changes in the pattern of hospital intravenous antimicrobial use in Saudi Arabia,
      2006-2008.
AB  - BACKGROUND AND OBJECTIVE: Hospitals should measure antimicrobial use based on the
      WHO's recommended metric, the defined daily dose (DDD). There is no data on
      antimicrobial usage based on DDD in Saudi Arabia. Thus, this study evaluates the
      trend in antimicrobial consumption based on this concept. DESIGN AND SETTING:
      Observational study in a general hospital in Saudi Arabia from 2006-2008.
      METHODS: We analyzed the use of intravenous systemic antibacterial agents (group
      J01 of the Anatomical Therapeutic Chemical [ATC] classification and the classes
      of this group) that were administered to hospitalized patients by reviewing the
      data obtained from the pharmacy records. Antimicrobial consumption was calculated
      as the number of DDD per 100 bed-days. RESULTS: Of the total parenteral
      antibiotics, ciprofloxacin was the most commonly used intravenous antibiotic
      (67.6%), followed by ceftriaxone (6%), cefazolin (5%), and imipenem-enzyme
      inhibitor (4.3%). The DDD per 100 patient-days usage of intravenous antimicrobial
      agents was as follows: J01MA02 ciprofloxacin (parenteral) 82.643, J01DD04
      ceftriaxone 7.447, J01DB02 cefazolin 6.166, J01DH51 imipenem-enzyme inhibitor
      5.234, J01MA12 levofloxacin 3.188, and J01XA01 vancomycin 2.97. Intravenous
      ciprofloxacin usage increased from 3.55 to 82.643 DDD/100 patient days.
      CONCLUSION: The study showed that the most commonly used intravenous systemic
      antimicrobial agent was ciprofloxacin. Thus, strategies are needed to
      specifically target these agents for prescribing improvement.

PMID- 22871623
TI  - Empirical antibiotic treatment and the risk of necrotizing enterocolitis and
      death in very low birth weight neonates.
AB  - BACKGROUND AND OBJECTIVES: Antibiotics are one of the most overused drugs in the
      neonatal unit. Our objective was to assess associations between the duration of
      the initial antibiotic course and subsequent necrotizing enterocolitis (NEC)
      and/or death in very low birth weight (VLBW) neonates with sterile initial
      postnatal culture results. DESIGN AND SETTING: A retrospective cohort analysis of
      VLBW neonates admitted to a tertiary center during the period from 1 January 2008
      to 31 december 2009. PATIENTS AND METHODS: The study included VLBW neonates who
      had been inborn and admitted to the neonatal intensive care unit within the first
      24 hours after birth. We used descriptive statistics to characterize the study
      population, and multivariate analyses to evaluate associations between therapy
      duration, prolonged empirical therapy, and subsequent NEC and/or death. RESULTS:
      Of 328 VLBW neonates admitted to our center, 207 (63%) survived >5 days and
      received initial empirical antibiotic treatment for >=5 days. The median duration
      of initial empirical antibiotic therapy was 7 days (range 5-10 days). those
      neonates were more likely to be of younger gestational age, lower birth weight,
      and to have lower Apgar scores (P<.001, .001 and .017, respectively). each
      empirical treatment day was associated with increased odds of death (or 1.45, CI
      1.24-1.69), NEC (or 1.32, CI 1.05-1.65), and the composite measure of NEC or
      death (or 2.13, CI 1.55-2.93). CONCLUSION: The use of prolonged initial empirical
      antibiotic therapy in VLBW neonates with initial sterile culture results may be
      associated with an increased risk of NEC or death and should be used with
      caution.

PMID- 22871624
TI  - Tuberculosis screening among health sciences students in Saudi Arabia in 2010.
AB  - BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is a major health threat in both
      developed and developing nations. The aim of this study was to determine the
      prevalence of reactivity to the Mantoux test or tuberculin skin test (TST) among
      health sciences students after an open case of TB infection was detected in one
      of the students. DESIGN AND SETTING: A cross-sectional screening survey among
      students of the Health Sciences College for Girls in Jeddah conducted in June
      2010. SUBJECTS AND METHODS: Students were screened using a standardized TST, and
      the bacillus Calmette-Guerin (BCG) scars were later inspected. RESULTS: Of 320
      students, only 296 (92.5%) participated in the survey. Thirty-five (12%) had a
      positive test reactivity (>=10 mm). Seventy-six (25.7%) students had no BCG
      vaccination scar. CONCLUSIONS: The prevalence of a positive TST was high among
      students when considered as a primary diagnostic method for latent Mycobacterium
      tuberculosis infection. Strengthening infection control measures is recommended
      during students' health care training.

PMID- 22871625
TI  - Dengue retinochoroiditis.
AB  - Dengue is a mosquito-borne infection caused by a flavivirus. I describe the
      ocular findings observed in two patients infected with dengue virus who presented
      with acute onset of loss of vision preceded by febrile illness, malaise,
      generalized fatigue headache, and maculopapular rash. Ophthalmologic evaluation
      in each patient revealed a normal anterior segment. Vitreous cells were noted in
      one patient. Ophthalmoscopy revealed multiple foci of retinochoroiditis,
      vasculitis, cotton-wool spots, and retinal hemorrhages. The healing of the lesion
      showed discrete atrophic and pigmented retinochoroiditic scars. Fluorescein
      angiography displayed early hypofluorescence and late hyperfluorescence
      suggestive of leakage. The healed scars showed late staining. The serologic
      testing showed elevated IgG antibodies, and one had high IgM antibodies to dengue
      virus. Ocular findings of dengue fever consist of multifocal areas of
      retinochoroiditis and may lead to loss of vision. In Saudi Arabia, dengue fever
      should be considered in the differential diagnosis of multifocal chorioretinal
      lesions and retinal vasculitis.

PMID- 22871626
TI  - Oro-cranial penetrating pencil injury.
AB  - Oro-cranial penetrating injuries are often seen in ear, nose and throat
      practices. Cases of penetrated pencil injuries are rarely reported despite being
      common in the developing world. A 7-year-old boy referred from a neighboring
      hospital was playing at school with the sharp end of a pencil in his mouth when
      he was pushed from behind by another child. He fell on his face and the sharp end
      of the pencil penetrated his throat with the distal end hanging out. There was no
      bleeding at presentation, as the pencil completely sealed the entrance point. The
      entrance point was at the posterior wall of the oropharynx corresponding to the
      uvulo-palatine junction. It penetrated posterosuperiorly through the soft tissue
      to reach the anterior part of the posterior cranial fossa. Since sharp and
      pointed objects in the upper aerodigestive tract can result in potentially fatal
      complications, prompt diagnosis, a systematic treatment protocol, and an
      experienced trauma team are necessary to prevent a potential catastrophe.

PMID- 22871627
TI  - Granular cell ameloblastoma showing desmoplasia.
AB  - Our case of ameloblastoma had a surprisingly long 25 year history, with
      abnormally large dimensions, a multilocular diffuse-mixed radiographic picture,
      and was histopathologically diagnosed as granular cell ameloblastoma with
      desmoplasia. To the best of our knowledge, this is the first ameloblastoma ever
      reported, that has shown combined features of granular cells, desmoplasia,
      ameloblastic follicles, plexiform, and acanthomatous patterns. The nature of
      granular cells in this type of tumor and the significance of their presence have
      also been reviewed. From the studies on ameloblastomas to date, it seems that the
      old belief that granular cell ameloblastoma is the most aggressive variant of
      ameloblastoma is a myth, and in all probability, granular cells are just a
      transitional or matured phase in the life cycle of ameloblastomas, starting with
      normal stellate reticulum-like cells, leading to a production of granules and
      finally leading to degeneration and formation of cystic areas.

PMID- 22871628
TI  - Sarcomatoid carcinoma of the cervix.
AB  - Sarcomatoid carcinoma is a rare pathological entity of the cervix. A case of FIGO
      stage III sarcomatoid carcinoma of the cervix is reported. The patient was
      treated with concurrent radiotherapy and chemotherapy. Despite the initial
      excellent local response to therapy, she developed an early metastatic disease.
      In a review of the published studies, only 19 cases were reported on this type of
      cervical cancer.

PMID- 22871629
TI  - A syndrome of congenital ichthyosis, mental retardation, myopathy and anemia in
      dizygotic twin sisters.

PMID- 22871630
TI  - RE: How do medical students in their clinical years perceive basic sciences
      courses at King Saud University?

PMID- 22871631
TI  - Hemorrhage and thrombosis hand in hand.

PMID- 22871632
TI  - IL-1RA injected intra-cisterna magna confers extended prophylaxis against
      lipopolysaccharide-induced neuroinflammatory and sickness responses.
AB  - IL-1RA has been used intra-cerebrally to ameliorate neuroinflammatory responses.
      The present study explored the possibility that the bioactivity of IL-1RA
      administered intra-cerebrally may be prolonged in the CNS. hIL-1RA was detected
      in hippocampus from 2h to 14d post-ICM treatment. hIL-1RA ameliorated both the
      hippocampal cytokine (TNFalpha and NFkappaBIalpha) and sickness response to
      peripheral LPS administered 4d after hIL-1RA. Four days post treatment, hIL-1RA
      reduced the basal expression of IL-1R1, Iba-1, MHCII, and TLR4 and blunted the
      microglial IL-1beta and IL-6 response to LPS ex vivo. IL-1RA might be
      administered prophylactically to prevent the neuroinflammatory effects of trauma.

PMID- 22871633
TI  - Altered natural killer cells' response to herpes virus infection in multiple
      sclerosis involves KIR2DL2 expression.
AB  - The role of herpes viruses as potential triggers of multiple sclerosis (MS) is
      still debated. Peripheral blood mononuclear cells from MS patients and controls
      were treated with CpG sequences and infected in vitro with HSV-1. Samples were
      analyzed for viral yield, TLR9 pathways, cytokine secretion, NK cell activation
      and killer immunoglobulin-like receptor (KIR) expression. CpG treatment promoted
      an unexpected sensitivity to herpes virus infection in a subset of MS patients:
      TLR9 pathways did not show defects while NK cells presented decreased
      degranulation and cytotoxicity and up-regulated the inhibitory KIR2DL2 receptor.
      CpG treatment of purified NK cells affected directly KIR2DL2 modulation and cell
      activation. These data suggest potential implications for viral pathogenesis of
      MS.

PMID- 22871634
TI  - HIV integrase as a target for antiretroviral therapy.
AB  - PURPOSE OF REVIEW: Integrase strand transfer inhibitors are the most recent class
      of antiretroviral agents to be introduced into clinical practice. This review
      describes the discovery of the first inhibitors and insights into their distinct
      mechanism of action with potential translational implications. RECENT FINDINGS:
      HIV replication depends on the successful integration of the viral genetic
      material into the host cell chromosome. The virally encoded enzyme integrase
      mediates both the DNA cutting and strand transfer or DNA joining steps which are
      required for this process. Understanding the mechanistic aspects of integration
      was critical for the initial discovery of integrase strand transfer inhibitors
      and the advancement of clinical candidates. The recent adoption of these
      inhibitors into clinic practice has now proven the therapeutic utility of the
      class. Integrase inhibitors are characterized by a more rapid decrease in viral
      load in HIV-1-infected patients initiating therapy and possess prolonged window
      for intervention in the viral life cycle, thus offering an advantage in the
      setting of HIV-1 chemoprevention. SUMMARY: The distinct biochemical and antiviral
      mechanism of action of integrase strand transfer inhibitors are directly relevant
      to understanding the clinical properties which are characteristic of the class
      and their potential significance for the use of these agents in both treatment
      and prevention.

PMID- 22871635
TI  - HIV integrase inhibitors in ART-experienced patients.
AB  - PURPOSE OF REVIEW: We review the most recent clinical trials of integrase
      inhibitors (INIs) in antiretroviral therapy (ART)-experienced patients, including
      trails of new strategies such as intensification and simplification therapy with
      this new class of compounds. RECENT FINDINGS: After the excellent results of the
      first-generation INIs [raltegravir (RAL) and elvitegravir] in the treatment of
      ART-experienced patients, dolutegravir--a new second-generation compound in this
      drug class--adds the possibility of rescuing ART-experienced patients after
      virologic failure to first-generation INIs like RAL. RAL may have a role in an
      intensification strategy--adding RAL to a suppressive ART therapy--that could
      have an effect in avoiding new cycles of infection and cellular activation. On
      the contrary, RAL has clearly shown efficacy in switching away from boosted
      protease inhibitors (PI/r). This simplification strategy may be an interesting
      option in patients suffering from side effects of boosted protease inhibitors. In
      simplification, the length of time of HIV suppression before the switch may be
      used as a marker of probable success. SUMMARY: In ART-experienced patients INIs
      are a new and exciting part of the armamentarium for the control of HIV
      replication. INIs could play an interesting role in strategies such as
      intensification or simplification.

PMID- 22871636
TI  - Correlation of coreceptor usage and disease progression.
AB  - PURPOSE OF REVIEW: Primary HIV-1 infection is usually initiated by viruses with
      an exclusive affinity for the C-C chemokine receptor type 5 (CCR5) coreceptor.
      Viral variants that are also able to bind the C-X-C chemokine receptor type 4
      (CXCR4) coreceptor arise during the course of the disease in about 50% of the
      infected individuals and their emergence is associated with a faster disease
      progression. In this article we provide a historical overview of the events that
      led to the discovery of the relationship between viral phenotype, coreceptor
      tropism and pathogenesis. RECENT FINDINGS: The prevalence of CCR5 and CXCR4-using
      viruses differs from study to study, but overall percentages of CXCR4 use
      fluctuate between 2.0 and 63.0%. The association between coreceptor use and
      disease stage is recognized, with the lowest X4 prevalence in seroconverters and
      the highest in the final stage of the disease. Up to date there are insufficient
      arguments to support an impact of coreceptor tropism on response to combined
      antiretroviral therapy (cART) or an impact of cART on coreceptor tropism
      evolution. SUMMARY: This review provides an overview of available data on
      coreceptor use in the different stages of the HIV-1 infection process. Although
      it is clear that CXCR4-using viruses emerge during the course of infection, the
      driving forces and mechanisms behind coreceptor switch remain largely unknown.

PMID- 22871637
TI  - Associations between nighttime traffic noise and sleep: the Finnish public sector
      study.
AB  - BACKGROUND: Associations between traffic noise and sleep problems have been
      detected in experimental studies, but population-level evidence is scarce.
      OBJECTIVES: We studied the relationship between the levels of nighttime traffic
      noise and sleep disturbances and identified vulnerable population groups.
      METHODS: Noise levels of nighttime-outdoor traffic were modeled based on the
      traffic intensities in the cities of Helsinki and Vantaa, Finland. In these
      cities, 7,019 public sector employees (81% women) responded to postal surveys on
      sleep and health. We linked modeled outdoor noise levels to the residences of the
      employees who responded to the postal survey. We used logistic regression models
      to estimate associations of noise levels with subjectively assessed duration of
      sleep and symptoms of insomnia (i.e., difficulties falling asleep, waking up
      frequently during the night, waking up too early in the morning, nonrestorative
      sleep). We also used stratified models to investigate the possibility of
      vulnerable subgroups. RESULTS: For the total study population, exposure to levels
      of nighttime-outside (L(night, outside)) traffic noise > 55 dB was associated
      with any insomnia symptom >= 2 nights per week [odds ratio (OR) = 1.32; 95%
      confidence interval (CI): 1.05, 1.65]. Among participants with higher trait
      anxiety scores, which we hypothesized were a proxy for noise sensitivity, the ORs
      for any insomnia symptom at exposures to L(night, outside) traffic noises 50.1-55
      dB and > 55 dB versus <= 45 dB were 1.34 (95% CI: 1.00, 1.80) and 1.61 (95% CI:
      1.07, 2.42), respectively. CONCLUSIONS: Nighttime traffic noise levels > 50 dB
      L(night, outside) was associated with insomnia symptoms among persons with higher
      scores for trait anxiety. For the total study population, L(night, outside) > 55
      dB was positively associated with any symptoms.

PMID- 22871638
TI  - Effect of X-ray irradiation on the elastic strain evolution in the mineral phase
      of bovine bone under creep and load-free conditions.
AB  - Both the load partitioning between hydroxyapatite (HAP) and collagen during
      compressive creep deformation of bone and the HAP residual strain in unloaded
      bone have been shown in previous synchrotron X-ray diffraction studies to be
      affected by the X-ray irradiation dose. Here, through detailed analysis of the X
      ray diffraction patterns of bovine bone, the effect of X-ray dose on (i) the rate
      of HAP elastic strain accumulation/shedding under creep conditions and (ii) the
      HAP lattice spacing and average root mean square (RMS) strain under load-free
      conditions are examined. These strain measurements exhibit three stages in
      response to increasing X-ray dose. Up to ~75 kGy (stage I) no effect of dose is
      observed, indicating a threshold behavior. Between ~75 and ~300 kGy (stage II) in
      unloaded bone the HAP d-spacing increases and the RMS strain decreases with dose,
      indicating strain relaxation of HAP. Furthermore, under constant compressive load
      creep conditions, the rate of compressive elastic strain accumulation in HAP
      decreases with increasing dose until, at ~115 kGy, it changes sign, indicating
      that the HAP phase is shedding load during creep deformation. These stage II
      behaviors are consistent with HAP-collagen interfacial damage, which allows the
      HAP elastic strain to relax within both the loaded and unloaded samples. Finally,
      for doses in excess of ~300 kGy (stage III, measured up to 7771 kGy) the HAP
      lattice spacing and RMS strain for load-free samples and the rate of HAP elastic
      strain shedding for crept samples remain independent of dose, suggesting a
      saturation of damage and/or stiffening of the collagen matrix due to
      intermolecular cross-linking.

PMID- 22871639
TI  - Biocompatibility and chemical reaction kinetics of injectable, settable
      polyurethane/allograft bone biocomposites.
AB  - Injectable and settable bone grafts offer significant advantages over pre-formed
      implants due to their ability to be administered using minimally invasive
      techniques and to conform to the shape of the defect. However, injectable
      biomaterials present biocompatibility challenges due to the potential toxicity
      and ultimate fate of reactive components that are not incorporated in the final
      cured product. In this study the effects of stoichiometry and triethylenediamine
      (TEDA) catalyst concentration on the reactivity, injectability, and
      biocompatibility of two component lysine-derived polyurethane (PUR) biocomposites
      were investigated. Rate constants were measured for the reactions of water (a
      blowing agent resulting in the generation of pores), polyester triol, dipropylene
      glycol (DPG), and allograft bone particles with the isocyanate-terminated
      prepolymer using an in situ attenuated total reflection Fourier transform
      infrared spectroscopy technique. Based on the measured rate constants, a kinetic
      model predicting the conversion of each component with time was developed.
      Despite the fact that TEDA is a well-known urethane gelling catalyst, it was
      found to preferentially catalyze the blowing reaction with water relative to the
      gelling reactions by a ratio >17:1. Thus the kinetic model predicted that the
      prepolymer and water proceeded to full conversion, while the conversions of
      polyester triol and DPG were <70% after 24h, which was consistent with leaching
      experiments showing that only non-cytotoxic polyester triol and DPG were released
      from the reactive PUR at early time points. The PUR biocomposite supported
      cellular infiltration and remodeling in femoral condyle defects in rabbits at
      8weeks, and there was no evidence of an adverse inflammatory response induced by
      unreacted components from the biocomposite or degradation products from the cured
      polymer. Taken together, these data underscore the utility of the kinetic model
      in predicting the biocompatibility of reactive biomaterials.

PMID- 22871640
TI  - Biocompatibility and biodegradability of Mg-Sr alloys: the formation of Sr
      substituted hydroxyapatite.
AB  - Magnesium is an attractive material for use in biodegradable implants due to its
      low density, non-toxicity and mechanical properties similar to those of human
      tissue such as bone. Its biocompatibility makes it amenable for use in a wide
      range of applications from bone to cardiovascular implants. Here we investigated
      the corrosion rate in simulated body fluid (SBF) of a series of Mg-Sr alloys,
      with Sr in the range of 0.3-2.5%, and found that the Mg-0.5 Sr alloy showed the
      slowest corrosion rate. The degradation rate from this alloy indicated that the
      daily Sr intake from a typical stent would be 0.01-0.02 mg day-1, which is well
      below the maximum daily Sr intake levels of 4 mg day-1. Indirect cytotoxicity
      assays using human umbilical vascular endothelial cells indicated that Mg-0.5 Sr
      extraction medium did not cause any toxicity or detrimental effect on the
      viability of the cells. Finally, a tubular Mg-0.5 Sr stent sample, along with a
      WE43 control stent, was implanted into the right and left dog femoral artery. No
      thrombosis effect was observed in the Mg-0.5 Sr stent after 3 weeks of
      implantation while the WE43 stent thrombosed. X-ray diffraction demonstrated the
      formation of hydroxyapatite and Mg(OH)2 as a result of the degradation of Mg-0.5
      Sr alloy after 3 days in SBF. X-ray photoelectron spectroscopy further showed the
      possibility of the formation of a hydroxyapatite Sr-substituted layer that
      presents as a thin layer at the interface between the Mg-0.5 Sr alloy and the
      corrosion products. We believe that this interfacial layer stabilizes the surface
      of the Mg-0.5 Sr alloy, and slows down its degradation rate over time.

PMID- 22871642
TI  - Actin cortex mechanics and cellular morphogenesis.
AB  - The cortex is a thin, crosslinked actin network lying immediately beneath the
      plasma membrane of animal cells. Myosin motors exert contractile forces in the
      meshwork. Because the cortex is attached to the cell membrane, it plays a central
      role in cell shape control. The proteic constituents of the cortex undergo rapid
      turnover, making the cortex both mechanically rigid and highly plastic, two
      properties essential to its function. The cortex has recently attracted
      increasing attention and its functions in cellular processes such as cytokinesis,
      cell migration, and embryogenesis are progressively being dissected. In this
      review, we summarize current knowledge on the structural organization,
      composition, and mechanics of the actin cortex, focusing on the link between
      molecular processes and macroscopic physical properties. We also highlight
      consequences of cortex dysfunction in disease.

PMID- 22871641
TI  - Influence of select extracellular matrix proteins on mesenchymal stem cell
      osteogenic commitment in three-dimensional contexts.
AB  - Growth factors have been shown to be powerful mediators of mesenchymal stem cell
      (MSC) osteogenic differentiation. However, their use in tissue engineered
      scaffolds not only can be costly but also can induce undesired responses in
      surrounding tissues. Thus, the ability to specifically promote MSC osteogenic
      differentiation in the absence of exogenous growth factors via the manipulation
      of scaffold material properties would be beneficial. The current work examines
      the influence of select extracellular matrix (ECM) proteins on MSC osteogenesis
      toward the goal of developing scaffolds with intrinsically osteoinductive
      properties. Fibrinogen (FG), fibronectin (FN) and laminin-1 (LN) were chosen for
      evaluation due to their known roles in bone morphogenesis or bone fracture
      healing. These proteins were conjugated into poly(ethylene glycol) diacrylate
      (PEGDA) hydrogels and their effects on encapsulated 10T1/2 MSCs were evaluated.
      Specifically, following 1week of culture, mid-term markers of various MSC
      lineages were examined in order to assess the strength and specificity of the
      observed osteogenic responses. PEG-LN gels demonstrated increased levels of the
      osteogenic transcription factor osterix relative to day 0 levels. In addition,
      PEG-FG and PEG-LN gels were associated with increased deposition of bone ECM
      protein osteocalcin relative to PEG-FN gels and day 0. Importantly, the
      osteogenic response associated with FG and LN appeared to be specific in that
      markers for chondrocytic, smooth muscle cell and adipocytic lineages were not
      similarly elevated relative to day 0 in these gels. To gain insight into the
      integrin dynamics underlying the observed differentiation results, initial
      integrin adhesion and temporal alterations in cell integrin profiles were
      evaluated. The associated results suggest that alpha(2), alpha(v) and alpha(6)
      integrin subunits may play key roles in integrin-mediated osteogenesis.

PMID- 22871643
TI  - Exercise capacity and ventricular function in patients treated for isolated
      pulmonary valve stenosis or tetralogy of Fallot.
AB  - BACKGROUND: We hypothesized 1) that long-term ventricular outcome and exercise
      capacity would be better in patients with isolated pulmonary valve stenosis (PS)
      treated with balloon pulmonary valvuloplasty (BPV) than in patients operated for
      tetralogy of Fallot (TOF), and 2) that ventricular outcome and exercise capacity
      would not be different in PS patients and healthy controls. METHODS: We included
      21 PS patients after BPV (16.2 +/- 5.2 years) and 21 patients operated for TOF
      (16.6 +/- 5.6 years), matching them for gender, age at treatment, and age at
      study. Patients underwent cardiovascular magnetic resonance (CMR) imaging,
      exercise testing, 12-lead ECG and 24-hour Holter monitoring for assessment of
      right ventricular (RV) size and function, pulmonary regurgitation (PR), exercise
      capacity and electrocardiographic status. Healthy controls for CMR imaging and
      exercise testing were matched for gender and age at study. RESULTS: RV volumes
      and PR percentage were significantly larger in TOF patients than in PS patients;
      biventricular ejection fraction (EF) was not different. PR was mild in most PS
      patients. RV end-systolic volume was significantly larger in PS patients than in
      healthy controls; RVEF was significantly lower. Both patient groups had similar
      exercise test results. Peak workload and VO(2) max. were significantly lower in
      PS patients than in healthy controls. CONCLUSIONS: Longstanding mild PR in PS
      patients can lead to an enlarged RV, reduced RV function and reduced exercise
      capacity. Despite more PR and larger RV volumes in TOF patients, exercise
      capacity and biventricular function are similar in both patient groups.

PMID- 22871644
TI  - Assessing the significance of Ruditapes philippinarum as a sentinel for sediment
      pollution: bioaccumulation and biomarker responses.
AB  - The present study assessed whether the bivalve Ruditapes philippinarum may be
      appropriately deployed as a bioindicator in monitoring transitional environments,
      in terms of bioaccumulation potential and biomarker responses. The concentrations
      of trace metals, PAHs and PCBs were determined in sediments and clam tissue, and
      biomarkers were estimated at various levels of biological complexity (i.e.
      metallothioneins, lipofuscins, survival-in-air and reburrowing behaviour).
      Sediments and clams were collected biannually in 2004 and 2005 at eight sites
      within Venice lagoon, which were influenced differently by natural and
      anthropogenic impacts. Results highlighted that the broad variations of pollutant
      concentrations in sediments were not consistent either with the body residuals or
      with the biomarker responses. Consequently, on the basis of the observed weak
      responsiveness and sensitivity to anthropogenic stressors we suggest a more
      cautious use for R. philippinarum as sentinel organism, at least in estuarine
      sediments in the north Adriatic transitional areas.

PMID- 22871645
TI  - Antifungal Activity of Salicylanilides and Their Esters with 4
      (Trifluoromethyl)benzoic Acid.
AB  - Searching for novel antimicrobial agents still represents a current topic in
      medicinal chemistry. In this study, the synthesis and analytical data of eighteen
      salicylanilide esters with 4-(trifluoromethyl)benzoic acid are presented. They
      were assayed in vitro as potential antimycotic agents against eight fungal
      strains, along with their parent salicylanilides. The antifungal activity of the
      presented derivatives was not uniform and moulds showed a higher susceptibility
      with minimum inhibitory concentrations (MIC) >= 0.49 umol/L than yeasts (MIC >=
      1.95 umol/L). However, it was not possible to evaluate a range of 4
      (trifluoromethyl)benzoates due to their low solubility. In general, the most
      active salicylanilide was N-(4-bromophenyl)-4-chloro-2-hydroxybenzamide and among
      esters, the corresponding 2-(4-bromophenylcarbamoyl)-5-chlorophenyl 4
      (trifluoromethyl) benzoate exhibited the lowest MIC of 0.49 umol/L. However, the
      esterification of salicylanilides by 4-(trifluoromethyl)benzoic acid did not
      result unequivocally in a higher antifungal potency.

PMID- 22871646
TI  - Echinoclerodane A: a new bioactive clerodane-type diterpenoid from a gorgonian
      coral Echinomuricea sp.
AB  - A new clerodane-type diterpenoid, echinoclerodane A (1), was isolated from a
      Formosan gorgonian coral Echinomuricea sp. The structure of 1 was elucidated by
      spectroscopic methods. Echinoclerodane A (1) is the first clerodane-type compound
      obtained from the marine organisms belonging to the phylum Cnidaria.
      Echinoclerodane A (1) exhibited moderate cytotoxicity toward MOLT-4, HL-60, DLD-1
      and LoVo tumor cells and inhibitory effects on the generation of superoxide anion
      and the release of elastase by human neutrophils.

PMID- 22871647
TI  - Antiplasmodial and leishmanicidal activities of 2-cyano-3-(4-phenylpiperazine-1
      carboxamido) quinoxaline 1,4-dioxide derivatives.
AB  - Malaria and leishmaniasis are two of the World's most important tropical
      parasitic diseases. Thirteen new 2-cyano-3-(4-phenylpiperazine-1-carboxamido)
      quinoxaline 1,4-dioxide derivatives (CPCQs) were synthesized and evaluated for
      their in vitro antimalarial and antileishmanial activity against erythrocytic
      forms of Plasmodium falciparum and axenic forms of Leishmania infantum. Their
      toxicity against VERO cells (normal monkey kidney cells) was also assessed. None
      of the tested compounds was efficient against Plasmodium, but two of them showed
      good activity against Leishmania. Toxicity on VERO was correlated with
      leishmanicidal properties.

PMID- 22871648
TI  - State-time spectrum of signal transduction logic models.
AB  - Despite the current wealth of high-throughput data, our understanding of signal
      transduction is still incomplete. Mathematical modeling can be a tool to gain an
      insight into such processes. Detailed biochemical modeling provides deep
      understanding, but does not scale well above relatively a few proteins. In
      contrast, logic modeling can be used where the biochemical knowledge of the
      system is sparse and, because it is parameter free (or, at most, uses relatively
      a few parameters), it scales well to large networks that can be derived by manual
      curation or retrieved from public databases. Here, we present an overview of
      logic modeling formalisms in the context of training logic models to data, and
      specifically the different approaches to modeling qualitative to quantitative
      data (state) and dynamics (time) of signal transduction. We use a toy model of
      signal transduction to illustrate how different logic formalisms (Boolean, fuzzy
      logic and differential equations) treat state and time. Different formalisms
      allow for different features of the data to be captured, at the cost of extra
      requirements in terms of computational power and data quality and quantity.
      Through this demonstration, the assumptions behind each formalism are discussed,
      as well as their advantages and disadvantages and possible future developments.

PMID- 22871649
TI  - Chemical composition of odorous secretions in the Tasmanian short-beaked echidna
      (Tachyglossus aculeatus setosus).
AB  - The short-beaked echidna is believed to use olfactory cues from a cloacal scent
      gland to attract and locate mates during the breeding season. We investigated the
      chemical composition of echidna secretions, including cloacal swabs and solid,
      "waxy" exudates from the cloaca and spurs. Scent samples from 37 individuals were
      collected over a 1-year period and analyzed using a range of different analytical
      techniques. A total of 186 compounds were identified, including volatile
      carboxylic acids, aldehydes, ketones, fatty acids, methyl esters, ethyl esters,
      terpenes, nitrogen- and sulphur-containing compounds, alcohols, and aromatics.
      Long chain and very long chain monounsaturated fatty acids, sterols, and sterol
      esters were identified as the major constituents of solid exudates, some of which
      have not previously been described from any animal skin gland. There was a high
      degree of composition overlap between male and female cloaca swabs; however,
      there is significant variation, which could mediate echidna mating behavior. Many
      of the volatile and nonvolatile chemicals detected are used for communication in
      other species, suggesting that chemical signals have important and diverse
      functions in echidna social interactions.

PMID- 22871650
TI  - Ex vivo culturing of whole, developing Drosophila brains.
AB  - We describe a method for ex vivo culturing of whole Drosophila brains. This can
      be used as a counterpoint to chronic genetic manipulations for investigating the
      cell biology and development of central brain structures by allowing acute
      pharmacological interventions and live imaging of cellular processes. As an
      example of the technique, prior work from our lab(1) has shown that a previously
      unrecognized subcellular compartment lies between the axonal and somatodendritic
      compartments of axons of the Drosophila central brain. The development of this
      compartment, referred to as the axon initial segment (AIS)(2), was shown
      genetically to depend on the neuron-specific cyclin-dependent kinase, Cdk5. We
      show here that ex vivo treatment of wild-type Drosophila larval brains with the
      Cdk5-specific pharmacological inhibitors roscovitine and olomoucine(3) causes
      acute changes in actin organization, and in localization of the cell-surface
      protein Fasciclin 2, that mimic the changes seen in mutants that lack Cdk5
      activity genetically. A second example of the ex vivo culture technique is
      provided for remodeling of the connections of embryonic mushroom body (MB) gamma
      neurons during metamorphosis from larva to adult. The mushroom body is the center
      of olfactory learning and memory in the fly(4), and these gamma neurons prune
      their axonal and dendritic branches during pupal development and then re-extend
      branches at a later timepoint to establish the adult innervation pattern(5).
      Pruning of these neurons of the MB has been shown to occur via local degeneration
      of neurite branches(6), by a mechanism that is triggered by ecdysone, a steroid
      hormone, acting at the ecdysone receptor B1(7), and that is dependent on the
      activity of the ubiquitin-proteasome system(6). Our method of ex vivo culturing
      can be used to interrogate further the mechanism of developmental remodeling. We
      found that in the ex vivo culture setting, gamma neurons of the MB recapitulated
      the process of developmental pruning with a time course similar to that in vivo.
      It was essential, however, to wait until 1.5 hours after puparium formation
      before explanting the tissue in order for the cells to commit irreversibly to
      metamorphosis; dissection of animals at the onset of pupariation led to little or
      no metamorphosis in culture. Thus, with appropriate modification, the ex vivo
      culture approach can be applied to study dynamic as well as steady state aspects
      of central brain biology.

PMID- 22871651
TI  - Phylogenetic analysis of nonstructural protein 5 (NSP5) gene sequences in porcine
      rotavirus B strains.
AB  - Porcine rotavirus B (RVB) has frequently been detected in the diarrhea of
      suckling and weaned pigs. Because it is difficult to propagate RVBs serially in
      cell culture, little genetic information about RNA segments other than VP7, NSP1
      and NSP2 is available for porcine RVBs. We conducted a phylogenetic analysis
      focusing on nonstructural protein 5 (NSP5) using 22 porcine RVB strains, which
      were identified in fecal samples collected around Japan. Sequence analysis showed
      that NSP5 genes of RVBs contain one ORF, in contrast to the corresponding gene of
      RVAs that have two ORFs. Comparison of NSP5 amino acid sequences from porcine
      RVBs with other RVBs revealed that eight serine and serine/threonine residues at
      the N- and C-terminal regions are highly conserved among RVBs. Phylogenetic
      analysis also indicated the presence of six clusters (H1-H6) including rat,
      human, porcine and bovine plus ovine clusters with cut-off values of 78% at the
      nucleotide level. Moreover, the NSP5 genes of porcine RVBs were divided to three
      clusters. The data presented here demonstrates that several porcine RVBs with
      distinctive genotypes are circulating among farms throughout Japan. Our findings
      provide important new insights into the evolutionary dynamics of RVBs.

PMID- 22871653
TI  - Health care reform: forget perfection and do what's possible.

PMID- 22871652
TI  - Babesia: a world emerging.
AB  - Babesia are tick-transmitted hemoprotozooans that infect mammals and birds, and
      which are acknowledged for their major impact on farm and pet animal health and
      associated economic costs worldwide. Additionally, Babesia infections of wildlife
      can be fatal if associated with stressful management practices; and human
      babesiosis, also transmitted by blood transfusion, is an increasing public-health
      concern. Due to the huge diversity of species reported to serve as Babesia hosts,
      all vertebrates might be potential carriers, as long as they are adequate hosts
      for Babesia-vector ticks. We here provide a comprehensive overview of the most
      relevant Babesia species, and a discussion of the classical taxonomic criteria.
      Babesia, Cytauxzoon and Theileria parasites are closely related and collectively
      referred to as piroplasmids. A possible scenario for the history of piroplasmids
      is presented in the context of recent findings, and its implications for future
      research avenues are outlined. Phylogenetic trees of all available 18S rRNA and
      hsp70 genes were generated, based on which we present a thoroughly revised
      molecular classification, comprising five monophyletic Babesia lineages, one
      Cytauxzoon clade, and one Theileria clade. Updated 18S rRNA and beta-tubulin gene
      trees of the B. microti isolates agree with those previously reported. To
      reconcile estimates of the origin of piroplasmids and ticks (~300 Ma,
      respectively), and mammalian radiation (60 Ma), we hypothesize that the dixenous
      piroplasmid life cycle evolved with the origin of ticks. Thus, the observed time
      gap between tick origin and mammalian radiation indicates the existence of
      hitherto unknown piroplasmid lineages and/or species in extant vertebrate taxa,
      including reptiles and possibly amphibians. The development and current status of
      the molecular taxonomy of Babesia, with emphasis on human-infecting species, is
      discussed. Finally, recent results from population genetic studies of Babesia
      parasites, and their implications for the development of pathogenicity, drug
      resistance and vaccines, are summarized.

PMID- 22871654
TI  - Next steps when BP won't come down.
AB  - A poor response to therapy should trigger a search for a secondary cause of
      hypertension. Use this review as your guide.

PMID- 22871655
TI  - How well are we managing diabetes in long-term care?
AB  - The care received by nursing home residents with diabetes does not meet ADA
      standards for ambulatory adults, this study finds. Nor should it. The frail
      elderly need new standards that address their particular needs.

PMID- 22871656
TI  - Eye pain: 5 cases to test your skill.
AB  - The ability to distinguish between ophthalmic emergencies and benign eye
      conditions is crucial for a family physician. Find out how your skills stack up.

PMID- 22871657
TI  - Meningococcal vaccine for infants?
AB  - With the incidence of meningococcal disease declining in all age groups, ACIP is
      weighing the need for vaccination in children <2 years.

PMID- 22871659
TI  - Painless cutaneous nodules.
AB  - The lesions on the patient's body were getting caught on his clothes. He said
      that his mother and several of his siblings had similar "lumps".

PMID- 22871660
TI  - Clinical Inquiry. Do inhaled steroids reduce bone mineral density and increase
      fracture risk?
AB  - No, except perhaps at high doses. Inhaled corticosteroids at low to medium doses
      (<1500 mcg beclomethasone hydrofluoroalkane per day) for asthma and chronic
      obstructive pulmonary disease don't increase the risk of significant bone loss or
      fracture at 2 to 3 years follow-up. Higher doses, however, may raise the risk of
      nontraumatic fracture over 1 to 4 years of follow-up.

PMID- 22871661
TI  - Clinical Inquiry. Multivitamins for healthy children: what are the true benefits?
AB  - The benefits appear to be limited. It's doubtful that multivitamin with mineral
      (MVM) supplementation improves IQ in healthy, low-risk children.

PMID- 22871662
TI  - Chemoselection of allogeneic HSC after murine neonatal transplantation without
      myeloablation or post-transplant immunosuppression.
AB  - The feasibility of allogeneic transplantation, without myeloablation or post
      transplant immunosuppression, was tested using in vivo chemoselection of
      allogeneic hematopoietic stem cells (HSCs) after transduction with a novel
      tricistronic lentiviral vector (MGMT(P140K)-2A-GFP-IRES-TK (MAGIT)). This vector
      contains P140K-O(6)-methylguanine-methyltransferase (MGMT(P140K)), HSV-thymidine
      kinase (TK(HSV)), and enhanced green fluorescent protein (eGFP) enabling (i) in
      vivo chemoselection of HSC by conferring resistance to benzylguanine (BG), an
      inhibitor of endogenous MGMT, and to chloroethylating agents such as 1,3-bis(2
      chloroethyl)nitrosourea (BCNU) and, (ii) depletion of proliferating cells such as
      malignant clones or transduced donor T cells mediating graft versus host disease
      (GVHD), by expression of the suicide gene TK(HSV) and Ganciclovir (GCV)
      administration. Non-myeloablative transplantation of transduced, syngeneic,
      lineage-depleted (Lin(-)) BM in neonates resulted in 0.67% GFP(+) mononuclear
      cells in peripheral blood. BG/BCNU chemoselection, 4 and 8 weeks post-transplant,
      produced 50-fold donor cell enrichment. Transplantation and chemoselection of
      major histocompatibility complex (MHC)-mismatched MAGIT-transduced Lin(-) BM also
      produced similar expansion for >40 weeks. The efficacy of this allotransplant
      approach was validated in Hbb(th3) heterozygous mice by correction of beta
      thalassemia intermedia, without toxicity or GVHD. Negative selection, by
      administration of GCV resulted in donor cell depletion without graft ablation, as
      re-expansion of donor cells was achieved with BG/BCNU treatment. These studies
      show promise for developing non-ablative allotransplant approaches using in vivo
      positive/negative selection.

PMID- 22871663
TI  - Phase II trial of intravenous administration of Reolysin((r)) (Reovirus Serotype
      3-dearing Strain) in patients with metastatic melanoma.
AB  - Reovirus, a replication competent RNA virus, has preclinical activity against
      melanoma lines and xenografts. We conducted a phase II trial of reovirus in
      metastatic melanoma patients. Patients received 3 * 10(10) TCID50 on days 1-5 of
      each 28 day cycle, administered intravenously. Twenty-one eligible patients were
      enrolled. Treatment was well tolerated without any dose reductions having to be
      implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15
      contained adequate tumor for correlative analysis. In two patients, productive
      reoviral replication (viral antigen coexpression with tubulin) was demonstrated,
      despite increase in neutralizing antibody titers. There were no objective
      responses although 75-90% tumor necrosis, consistent with treatment effect, was
      observed in one patient who had metastatic lesions surgically removed. Median
      time to progression and survival were 45 days (range 13-96 days) and 165 days
      (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was
      well tolerated in metastatic melanoma patients; viral replication was
      demonstrated in biopsy samples. Based on preclinical data showing synergy with
      taxane and platinum compounds, a phase II combination trial in metastatic
      melanoma patients is ongoing.

PMID- 22871664
TI  - High-efficiency transduction of rhesus hematopoietic repopulating cells by a
      modified HIV1-based lentiviral vector.
AB  - Human immunodeficiency virus type 1 (HIV1) vectors poorly transduce rhesus
      hematopoietic cells due to species-specific restriction factors, including the
      tripartite motif-containing 5 isoformalpha (TRIM5alpha) which targets the HIV1
      capsid. We previously developed a chimeric HIV1 (chiHIV) vector system wherein
      the vector genome is packaged with the simian immunodeficiency virus (SIV) capsid
      for efficient transduction of both rhesus and human CD34(+) cells. To evaluate
      whether chiHIV vectors could efficiently transduce rhesus hematopoietic
      repopulating cells, we performed a competitive repopulation assay in rhesus
      macaques, in which half of the CD34(+) cells were transduced with standard SIV
      vectors and the other half with chiHIV vectors. As compared with SIV vectors,
      chiHIV vectors achieved higher vector integration, and the transgene expression
      rates were two- to threefold higher in granulocytes and red blood cells and
      equivalent in lymphocytes and platelets for 2 years. A recipient of chiHIV vector
      only transduced cells reached up to 40% of transgene expression rates in
      granulocytes and lymphocytes and 20% in red blood cells. Similar to HIV1 and SIV
      vectors, chiHIV vector frequently integrated into gene regions, especially into
      introns. In summary, our chiHIV vector demonstrated efficient transduction for
      rhesus long-term repopulating cells, comparable with SIV vectors. This chiHIV
      vector should allow preclinical testing of HIV1-based therapeutic vectors in
      large animal models.

PMID- 22871665
TI  - Administration of anti-CD3 antibodies modulates the immune response to an
      infusion of alpha-glucosidase in mice.
AB  - Animal and human studies of enzyme replacement therapy (ERT) for Pompe disease
      (PD) have indicated that antibodies (Abs) generated against infused recombinant
      human alpha-glucosidase (rhGAA) can have a negative impact on the therapeutic
      outcome and cause hypersensitivity reactions. We showed that parenteral
      administration of anti-CD3 Abs into mice can reduce the titer of anti-human GAA
      Abs in wild-type mice administered the enzyme. Mice that had been treated with
      anti-CD3 Abs and then subjected to a secondary challenge with rhGAA showed a
      lower increase in Ab titers than control mice. Moreover, the administration of
      anti-CD3 Abs also reduced the levels of pre-existing Abs. Treatment with anti-CD3
      Abs also prevented a lethal hypersensitivity reaction and reduced the Ab titers
      in a mouse model of PD. Mice treated with anti-CD3 Abs showed reduced numbers of
      CD4(+) and CD8(+) cells, and an increased ratio of CD4(+)CD25(+)/CD4(+) and
      CD4(+)CD25(+)FoxP3(+)/CD4(+) cells. When the CD4(+)CD25(+) cells were depleted
      using anti-CD25 Abs, the observed reduction in Abs against the enzyme by anti-CD3
      Abs was abrogated. This suggests that CD4(+)CD25(+) cells are important for the
      immune suppressive activity of anti-CD3 Abs. In summary, anti- CD3 Abs are useful
      for inducing immune tolerance to ERT for PD.

PMID- 22871666
TI  - In vivo selection of transplanted hepatocytes by pharmacological inhibition of
      fumarylacetoacetate hydrolase in wild-type mice.
AB  - Genetic fumarylacetoacetate hydrolase (Fah) deficiency is unique in that healthy
      gene-corrected hepatocytes have a strong growth advantage and can repopulate the
      diseased liver. Unfortunately, similar positive selection of gene-corrected cells
      is absent in most inborn errors of liver metabolism and it is difficult to reach
      the cell replacement index required for therapeutic benefit. Therefore, methods
      to transiently create a growth advantage for genetically modified hepatocytes in
      any genetic background would be advantageous. To mimic the selective pressure of
      Fah deficiency in normal animals, an efficient in vivo small molecule inhibitor
      of FAH, 4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate (CEHPOBA) was
      developed. Microarray analysis demonstrated that pharmacological inhibition of
      FAH produced highly similar gene expression changes to genetic deficiency. As
      proof of principle, hepatocytes lacking homogentisic acid dioxygenase (Hgd) and
      hence resistant to FAH inhibition were transplanted into sex-mismatched wild-type
      recipients. Time course analyses of 4-6 weeks of CEHPOBA administration after
      transplantation showed a linear relationship between treatment length and
      replacement index. Compared to controls, recipients treated with the FAH
      inhibitor had 20-100-fold increases in liver repopulation. We conclude that
      pharmacological inhibition of FAH is a promising approach to in vivo selection of
      hepatocytes.

PMID- 22871669
TI  - Enhanced electronic correlation and thermoelectric response by Cu-doping in
      Ca3Co4O9 single crystals.
AB  - The structure, anisotropic magnetic, electrical and thermal transport properties
      for single crystals of Ca(3)Co(4-x)Cu(x)O(9) (x = 0, 0.2, 0.4, 0.6 and 0.8) have
      been investigated systematically. The Cu-doping with x = 0.2 at Co-site is
      sufficient to drive the low-temperature spin-glass state in the Ca(3)Co(4)O(9)
      system. The value of resistivity along ab-plane decreases monotonously with
      increasing x in the whole temperature range studied, and around room temperature,
      the in-plane resistivity of Ca(3)Co(3.2)Cu(0.8)O(9) is about 71% smaller than
      that of the undoped sample. The temperature region where the Fermi-liquid
      transport mechanism dominates becomes remarkably narrowed due to the Cu-doping
      while the electronic correlation in the system is enhanced. With further addition
      of Cu in the Ca(3)Co(4)O(9) system, the in-plane thermopower (S(ab)) increases
      slowly and the room-temperature S(ab) for Ca(3)Co(3.2)Cu(0.8)O(9) is about 17%
      larger than that of the undoped sample. As a result, the power factor along the
      ab-plane is enhanced by about 3.8 times compared to the undoped sample. The
      results are suggested to originate from the variations of carrier concentration
      and electronic correlation in this system via the different Cu-doping states:
      Cu(3+)/Cu(2+) (Cu(3+) major) into the CoO(2) layer for x <= 0.4, while
      Cu(2+)/Cu(3+) (Cu(2+) major) into the Ca(2)CoO(3) layers for x > 0.4.

PMID- 22871667
TI  - Ad3-hTERT-E1A, a fully serotype 3 oncolytic adenovirus, in patients with
      chemotherapy refractory cancer.
AB  - Twenty-five patients with chemotherapy refractory cancer were treated with a
      fully serotype 3-based oncolytic adenovirus Ad3-hTERT-E1A. In mice, Ad3 induced
      higher amounts of cytokines but less liver damage than Ad5 or Ad5/3. In humans,
      the only grade 3 adverse reactions were self-limiting cytopenias and generally
      the safety profile resembled Ad5-based oncolytic viruses. Patients that had been
      previously treated with Ad5 viruses presented longer lasting lymphocytopenia but
      no median increase in Ad3-specific T-cells in blood, suggesting immunological
      activity against antigens other than Ad3 hexon. Frequent alterations in antitumor
      T-cells in blood were seen regardless of previous virus exposure. Neutralizing
      antibodies against Ad3 increased in all patients, whereas Ad5 neutralizing
      antibodies remained stable. Treatment with Ad3-hTERT-E1A resulted in re-emergence
      of Ad5 viruses from previous treatments into blood and vice versa. Signs of
      possible efficacy were seen in 11/15 (73%) patients evaluable for tumor markers,
      four of which were treated only intravenously. Particularly promising results
      were seen in breast cancer patients and especially those receiving concomitant
      trastuzumab. Taken together, Ad3-hTERT-E1A seems safe for further clinical
      testing or development of armed versions. It offers an immunologically attractive
      alternative, with possible pharmacodynamic differences and a different receptor
      compared to Ad5.

PMID- 22871668
TI  - A TLR and non-TLR mediated innate response to lentiviruses restricts hepatocyte
      entry and can be ameliorated by pharmacological blockade.
AB  - Lentiviral vector (LV)-mediated gene transfer is a promising method of gene
      therapy. We previously reported that systemic injection of HIV-based LV triggers
      a transient inflammatory response. Here, we carried out studies to better
      characterize this response, and to develop a strategy to overcome the adverse
      effects of interferon (IFN) on LV-mediated gene transfer. We profiled gene
      expression in the liver after LV administration using deep-sequencing (RNA-seq),
      and identified several innate response pathways. We examined the response to LV
      in MyD88-TRIF knockout mice, which are incapable of toll-like receptor (TLR)
      signaling. Unexpectedly, the IFN response to LV was not reduced in the liver
      indicating that a non-TLR pathway can recognize LV in this organ. Indeed,
      blocking reverse transcription with azidothymidine (AZT) reduced the IFN response
      only in the liver, suggesting that proviral DNA can be a trigger. To block the
      inflammatory response, we pretreated mice with a short course of dexamethasone
      (Dex). At 4 hours post-treatment, all the IFN-induced genes were normalized. By
      blocking the inflammatory response, hepatocyte transduction was dramatically
      increased, which in turn doubled the level of human factor IX (FIX) produced by a
      hepatocyte-specific LV. Our studies uncover new insights into LV-induced immune
      responses in the liver, and provide a means to increase the safety and efficiency
      of LV-mediated gene transfer.

PMID- 22871670
TI  - [Evaluation of professional practices: improving cancer related-pain management
      in radiation oncology].
AB  - Radiation oncologist often faced cancer pain, regardless the stage of cancer.
      Given the high prevalence of cancer pain, and its potential for profound adverse
      consequences, all patients with active malignancy should be routinely screened
      and treated for pain. Using a questionnaire developed by the pain center of the
      Institut de cancerologie de la Loire, we questioned in a routine day 154 patients
      receiving radiation in our department. On 154 assessed patients, 92% (n = 143)
      were treated with curative intent and 8% (n = 11) with analgesic intent. Sixty
      seven (44%) and 14 (9%) declared to feel pain outside and during radiotherapy,
      respectively. Using the visual analogic scale, 39, 41 and 20% rated their pain
      between 1 and 3, 4 and 6 and more than 7, respectively. One third of patients
      suffering from pain had no analgesic treatment and 55% of patients felt
      inadequately relieved. Almost all (97%) of these noted an impact on their quality
      of life. Half of them (54%) were aware of a specific consultation for pain. A
      pain consultation was offered to 19% of respondents and 26% of patients were
      referred for a specialized consultation at the end of the investigation. Despite
      the existence of a pain center in the Institute, the pain seems insufficiently
      assessed and supported for patients receiving radiation therapy. Better
      communication between caregivers and better information should enable a more
      comprehensive assessment and specific treatment for cancer-pain related.

PMID- 22871671
TI  - Recombinant haemagglutinin protein of highly pathogenic avian influenza A (H5N1)
      virus expressed in Pichia pastoris elicits a neutralizing antibody response in
      mice.
AB  - Recombinant avian influenza vaccines offer several advantages over the
      conventional vaccines. In this study, the haemagglutinin (HA) gene of highly
      pathogenic avian influenza H5N1 was cloned and expressed as His tagged protein in
      methylotropic yeast Pichia pastoris. The expression of recombinant HA (rHA)
      protein was confirmed by SDS-PAGE and western blot analysis. The rHA protein was
      purified using Ni-NTA affinity chromatography under denaturing conditions and the
      functions of the protein was assessed by the haemagglutinin assay after
      refolding. The immunogenicity of the rHA was evaluated by immunizing four groups
      of mice with different payloads (2.5, 5.0, 10 and 25MUg) of purified rHA and the
      production of rHA specific antibodies were analysed by haemagglutinin inhibition
      assay (HI) and enzyme-linked immunosorbent assay (ELISA). An antigen specific
      immune response was observed against rHA indicating that the rHA antigen could be
      used as a vaccine candidate against avian influenza. These results suggest that
      this strategy would pave the way for the development of rapid and cost effective
      method for the production of an avian influenza vaccine.

PMID- 22871672
TI  - Minor groove binder modification of widely used TaqMan probe for hepatitis E
      virus reduces risk of false negative real-time PCR results.
AB  - Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in many parts
      of the developing world. It is responsible for both sporadic infections and large
      scale epidemics and may be associated with significant mortality during
      pregnancy. Over the past two decades many serological and nucleic acid based
      diagnostic tests for HEV have been developed, including several reverse
      transcription real-time polymerase chain reaction assays (RT-qPCR). One of the
      most widely used of these RT-qPCRs is that developed by Jothikumar and colleagues
      (Journal of Virological Methods 2006, 131, 65-71). Whilst reviewing this assay we
      calculated the predicted melting temperature of its TaqMan probe and consequently
      synthesised a minor groove binder (MGB) version in order to increase its
      hybridisation stability. In this report the performance of the original
      unmodified probe is compared with that of the MGB-modified version. We
      demonstrate that the MGB-modified probe detected HEV RNA in plasma samples from
      six patients with serologically confirmed hepatitis E in whom the unmodified
      probe had failed to detect HEV RNA. Sequence analysis of the ORF3 segment
      targeted by the RT-qPCR was possible in 4 of the 6 patients and revealed an
      identical C->T single nucleotide mutation in the probe binding region in each
      case.

PMID- 22871673
TI  - Role of sea water DIP and DOP in controlling bulk alkaline phosphatase activity
      in N.W. Mediterranean Sea (Toulon, France).
AB  - The regulation of alkaline phosphatase activity by dissolved inorganic (DIP) and
      organic phosphorus (DOP) and the contribution of DOP as phosphorus source were
      studied monthly in Toulon Bay (NW Mediterranean, France) in 2005-2006. The
      concentrations of DIP and DOP varied respectively from 0 to 0.185MUM and from 0
      to 0.329MUM. The bulk activities (Vm, Km, Vm/Km) were measured using MUFP as
      substrate. Its high affinity component (Km: 0.05-1.00MUM) was negatively
      correlated with the sum of the concentrations of DIP and DOP but not with these
      compounds taken independently. A negative correlation with DIP was found when the
      concentrations of DOP were lower than 0.08MUM. A negative correlation with DOP
      was shown when the concentrations of DIP were lower than 0.05MUM. This high
      affinity component can be considered as a valuable indicator for the potential
      utilization of the compounds which contribute to the intracellular phosphorus
      pool.

PMID- 22871674
TI  - Fast and reversibly switchable wettability induced by a photothermal effect.
AB  - We report a novel approach for the fabrication of a photo-responsive surface with
      fast and reversibly switchable wettability between hydrophobicity and
      hydrophilicity induced by a photothermal effect.

PMID- 22871675
TI  - Novel role for the incretins in blood pressure regulation.
AB  - PURPOSE OF REVIEW: Incretin-based therapies are currently being used in the
      treatment of type 2 diabetes mellitus (T2DM). Apart from glycemic control, these
      agents have been shown to have multiple extra-pancreatic effects, including their
      role in blood pressure (BP) regulation. This article will review the origins of
      incretins, the incretin axis, possible mechanisms of antihypertensive effect of
      these agents, as well as the recent evidence. RECENT FINDINGS: Preclinical and
      clinical studies demonstrate the antihypertensive effects of glucagon-like
      peptide-1 (GLP-1) and its analogs in patients with T2DM and hypertension. This
      effect seems to be mediated through vasodilatation as well as modulation of renal
      sodium handling causing natriuresis, although the exact mechanisms are not fully
      known. SUMMARY: Incretin-based therapies are emerging as a novel class of
      hypoglycemic agents that display antihypertensive properties. Given the small
      decreases in BP, it is unlikely that these agents will be used as stand-alone
      antihypertensive agents, but they may be an attractive option in patients with
      T2DM and hypertension.

PMID- 22871676
TI  - Strategies for combination therapy in hypertension.
AB  - PURPOSE OF REVIEW: To achieve the target blood pressure (BP) mandated by current
      guidelines, a large majority of patients require simultaneous administration of
      multiple antihypertensive agents. The purpose of this review is to focus
      attention on the rational selection of effective drug combinations, and upon ways
      to use them efficiently to achieve therapeutic objectives. The topic is widely
      relevant given that more than 46  million ambulatory care visits are conducted in
      the United States annually for hypertension management. RECENT FINDINGS:
      Recommended drug combinations exhibit complimentary pharmacology and additive BP
      reduction, are well tolerated, and include components with demonstrated endpoint
      reduction in long-term clinical trials. Recently, the choice of diuretics has
      emerged as a controversial issue with some evidence favoring the long-acting
      agent, chlorthalidone, in preference to hydrochlorothiazide. For resistant
      hypertension, mineralocorticoid antagonists are increasingly used as preferred
      add-on agents. Practical strategies for the optimal use of combination therapy
      continue to evolve from the older stepped-care approach to the use of low-dose
      combinations, and to initiation of combination therapy in a broader range of
      hypertensive patients. SUMMARY: Thoughtful use of drug combinations is critical
      for achieving therapeutic objectives in hypertensive individuals and populations 
      more rapid BP control and more effective endpoint reduction. Practical
      strategies for the optimal use of combination therapy continue to evolve from the
      older stepped-care approach to more recent recommendations favoring the use of
      low-dose combinations, and initiation therapy of combination treatment,
      particularly in patients with Stage 2 hypertension.

PMID- 22871677
TI  - Atrial fibrillation and the risk of ischemic stroke: does it still matter in
      patients with a CHA2DS2-VASc score of 0 or 1?
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is an independent risk factor
      for stroke. Recent studies have demonstrated that the CHA(2)DS(2)-VASc scheme is
      useful for selecting patients who are truly at low risk. The goal of the present
      study was to compare the risk of ischemic stroke among AF patients with a
      CHA(2)DS(2)-VASc score of 0 (male) or 1 (female) with those without AF. METHODS:
      The study enrolled 509 males (CHA(2)DS(2)-VASc score=0) and 320 females
      (CHA(2)DS(2)-VASc score=1) with AF who did not receive any antithrombotic
      therapy. Patients were selected from the National Health Insurance Research
      Database in Taiwan. For each study patient, 10 age-matched and sex-matched
      subjects without AF and without any comorbidity from the CHA(2)DS(2)-VASc scheme
      were selected as controls. The clinical end point was the occurrence of ischemic
      stroke. RESULTS: During a follow-up of 57.4 +/- 35.7 months, 128 patients (1.4%)
      experienced ischemic stroke. The event rate did not differ between groups with
      and without AF for male patients (1.6% vs 1.6%; P=0.920). In contrast, AF was a
      significant risk factor for ischemic stroke among females (hazard ratio, 7.77),
      with event rates of 4.4% and 0.7% for female patients with and without AF
      (P<0.001). CONCLUSIONS: AF males with a CHA(2)DS(2)-VASc score of 0 were at true
      low risk for stroke, which was similar to that of non-AF patients. However, AF
      females with a score of 1 were still at higher risk for ischemic events than non
      AF patients.

PMID- 22871678
TI  - Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter
      electrocardiography for detection of paroxysmal atrial fibrillation after stroke.
AB  - BACKGROUND AND PURPOSE: Cardioembolism in paroxysmal atrial fibrillation (pxAF)
      is a frequent cause of ischemic stroke. Sensitive detection of pxAF after stroke
      is crucial for adequate secondary stroke prevention; the optimal diagnostic
      modality to detect pxAF on stroke units is unknown. We compared 24-hour Holter
      electrocardiography (ECG) with continuous stroke unit ECG monitoring (CEM) for
      pxAF detection. METHODS: Patients with acute ischemic stroke or transient
      ischemic attack were prospectively enrolled. After a 12-channel ECG on admission,
      all patients received 24-hour Holter ECG and CEM. Additionally, ECG monitoring
      data underwent automated analysis using dedicated software to identify pxAF.
      Patients with a history of atrial fibrillation or with atrial fibrillation on the
      admission ECG were excluded. RESULTS: Four hundred ninety-six patients (median
      age, 69 years; 61.5% male) fulfilled all inclusion criteria (ischemic stroke:
      80.4%; transient ischemic attack: 19.6%). Median stroke unit stay lasted 88.8
      hours (interquartile range, 65.0-122.0). ECG data for automated CEM analysis were
      available for a median time of 64.0 hours (43.0-89.8). Paroxysmal AF was
      documented in 41 of 496 patients (8.3%). Of these, Holter detected pxAF in 34.1%;
      CEM in 65.9%; and automated CEM in 92.7%. CEM and automated CEM detected
      significantly more patients with pxAF than Holter (P<0.001), and automated CEM
      detected more patients than CEM (P<0.001). CONCLUSIONS: Automated analysis of CEM
      improves pxAF detection in patients with stroke on stroke units compared with 24
      hour Holter ECG. The comparative usefulness of prolonged or repetitive Holter ECG
      recordings requires further evaluation.

PMID- 22871679
TI  - Detection of paroxysmal atrial fibrillation by 30-day event monitoring in
      cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time
      (SMART) Registry.
AB  - BACKGROUND AND PURPOSE: Patients with cryptogenic ischemic stroke may have
      undetected paroxysmal atrial fibrillation (PAF). We established the Stroke and
      Monitoring for PAF in Real Time (SMART) Registry to determine the yield of 30-day
      outpatient PAF monitoring in cryptogenic ischemic stroke. METHODS: The SMART
      Registry was a 3-year, prospective multicenter registry of 239 patients with
      cryptogenic ischemic stroke undergoing 30-day outpatient autotriggered PAF
      detection in Kaiser Permanente Northern California. RESULTS: In intention-to
      monitor analysis, PAF was detected in 29 of 239 patients (12.1%; 95% CI, 8.6%
      16.9%). After retrospective chart review was performed, a new diagnosis of PAF
      was confirmed in 26 of 236 patients (11.0%; 95% CI, 7.6%-15.7%). The majority of
      detected PAF events were asymptomatic; only 6 of 98 recorded PAF events (6.1%)
      were patient-triggered or associated with symptoms. CONCLUSIONS: -Approximately 1
      in every 9 patients with cryptogenic ischemic stroke was found to have new PAF
      within 30 days. Routine monitoring in this population should be strongly
      considered.

PMID- 22871680
TI  - Lung function as a risk factor for subarachnoid hemorrhage: a prospective cohort
      study.
AB  - BACKGROUND AND PURPOSE: The etiology of subarachnoid hemorrhage (SAH) is poorly
      understood. Reduced lung function, expressed as low forced expiratory volume in 1
      second (FEV(1)) and low forced vital capacity (FVC), is a predictor of
      cardiovascular disease, but whether reduced lung function is a risk factor for
      SAH is not known. The association between lung function and incidence of SAH was
      investigated in a prospective cohort study. METHODS: Between 1974 and 1992, 20
      534 men and 7237 women (mean age, 44 years) were examined in a health screening
      program including spirometry. The incidence of SAH was studied during a mean
      follow-up of 26 years in relation to age- and height-standardized FEV(1), FVC,
      and FEV(1)/FVC. RESULTS: One hundred forty-five subjects had a SAH (18.3 per 100
      000 person-years in men and 26.5 per 100 000 person-years in women). The hazard
      ratio for SAH in the lowest compared to the highest quartile of FEV(1) and
      FEV(1)/FVC was 2.24 (95% CI, 1.32-3.81; P for trend=0.014) and 1.92 (95% CI, 1.14
      3.23; P for trend=0.003), respectively, after adjustment for several confounding
      factors including smoking and hypertension. The results persisted when analysis
      was restricted to nonsmokers. FVC showed no significant association with
      incidence of SAH. CONCLUSIONS: Baseline lung function, expressed as low FEV(1) or
      FEV(1)/FVC, is a risk factor for SAH, independently of smoking.

PMID- 22871681
TI  - Vitamin supplementation and stroke prevention.

PMID- 22871682
TI  - Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a
      systematic review and meta-analysis update.
AB  - BACKGROUND AND PURPOSE: Endothelin is considered to be a key mediator of
      vasospasm after subarachnoid hemorrhage. A meta-analysis of randomized trials on
      the effectiveness of endothelin receptor antagonists in subarachnoid hemorrhage
      has been published previously, but since then new major trials have been
      published. We present the results of a systematic review and meta-analysis
      update. METHODS: We searched the Cochrane Library, the Cochrane Central Register
      of Controlled Trials, and PubMed with the following terms: subarachnoid
      hemorrhage AND (endothelin receptor antagonist OR clazosentan OR TAK-044 OR
      bosentan). All randomized, placebo-controlled trials investigating the effect of
      any endothelin receptor antagonists in patients with subarachnoid hemorrhage were
      included. Primary outcome was poor functional outcome (defined as death or
      dependency). Secondary outcomes were vasospasm, cerebral infarction as defined by
      investigators, and case fatality during follow-up. Data were pooled and effect
      sizes were expressed as risk ratio (RR) estimates with 95% confidence intervals
      (CI). We also calculated RR for several common complications. RESULTS: in 5
      trials with 2601 patients, endothelin receptor antagonists did not affect
      functional outcome (RR, 1.06: 95% CI, 0.93-1.22) despite a decreased incidence of
      angiographic vasospasm (RR, 0.58; 95% CI, 0.48-0.71). No effect was observed on
      vasospasm-related cerebral infarction (RR, 0.76; 95% CI, 0.53-1.11), any new
      cerebral infarction (RR, 1.04; 95% CI, 0.91-1.19), or case-fatality (RR, 1.04;
      95% CI, 0.78-1.39). Endothelin receptor antagonists increased the risk of lung
      complications (RR, 1.79; 95% CI, 1.52-2.11), pulmonary edema (RR, 2.12; 95% CI,
      1.32-3.39), hypotension (RR, 2.42: 95% CI, 1.78-3.29), and anemia (RR, 1.47; 95%
      CI, 1.19-1.83). CONCLUSION: These results argue against the use of endothelin
      receptor antagonists in patients with subarachnoid hemorrhage.

PMID- 22871683
TI  - The combined impact of virtual reality neurorehabilitation and its interfaces on
      upper extremity functional recovery in patients with chronic stroke.
AB  - BACKGROUND AND PURPOSE: Although there is strong evidence on the beneficial
      effects of virtual reality (VR)-based rehabilitation, it is not yet well
      understood how the different aspects of these systems affect recovery.
      Consequently, we do not exactly know what features of VR neurorehabilitation
      systems are decisive in conveying their beneficial effects. METHODS: To
      specifically address this issue, we developed 3 different configurations of the
      same VR-based rehabilitation system, the Rehabilitation Gaming System, using 3
      different interface technologies: vision-based tracking, haptics, and a passive
      exoskeleton. Forty-four patients with chronic stroke were randomly allocated to
      one of the configurations and used the system for 35 minutes a day for 5 days a
      week during 4 weeks. RESULTS: Our results revealed significant within-subject
      improvements at most of the standard clinical evaluation scales for all groups.
      Specifically we observe that the beneficial effects of VR-based training are
      modulated by the use/nonuse of compensatory movement strategies and the specific
      sensorimotor contingencies presented to the user, that is, visual feedback versus
      combined visual haptic feedback. CONCLUSIONS: Our findings suggest that the
      beneficial effects of VR-based neurorehabilitation systems such as the
      Rehabilitation Gaming System for the treatment of chronic stroke depend on the
      specific interface systems used. These results have strong implications for the
      design of future VR rehabilitation strategies that aim at maximizing functional
      outcomes and their retention.  Clinical Trial Registration- This trial was not
      registered because it is a small clinical study that evaluates the feasibility of
      prototype devices.

PMID- 22871684
TI  - Predictors and clinical features of postoperative hyperperfusion after surgical
      revascularization for moyamoya disease: a serial single photon emission
      CT/positron emission tomography study.
AB  - BACKGROUND AND PURPOSE: Clinical features and pathophysiology of postoperative
      hyperperfusion in moyamoya disease are still unclear. This study was aimed to
      clarify the incidence and time course of postoperative hyperperfusion and to
      determine the independent predictors of postoperative hyperperfusion in moyamoya
      disease. METHODS: This prospective study included 41 patients who underwent
      surgical revascularization for moyamoya disease. Using (15)O-gas positron
      emission tomography, hemodynamic and metabolic parameters were quantified before
      surgery. Using single photon emission computed tomography, cerebral blood flow
      was serially measured just after surgery and on 2 and 7 days postsurgery. A
      multivariate logistic regression analysis was conducted to test the effect of
      multiple variables on postoperative hyperperfusion. RESULTS: Postoperative
      hyperperfusion was observed in 29 (50.0%) of 58 operated hemispheres. The
      incidence of both radiological and symptomatic hyperperfusion was significantly
      higher in adult patients than in pediatric ones (P=0.026 and P=0.0037,
      respectively). Hyperperfusion just after surgery more often led to subsequent
      neurological deficits (P=0.033). A multivariate analysis revealed that
      preoperative cerebral blood volume increase was an independent predictor of both
      radiological and symptomatic hyperperfusion after surgery in adult moyamoya
      disease (OR, 6.6 and 12.3, respectively). CONCLUSIONS: Postoperative
      hyperperfusion after surgical revascularization is not rare in moyamoya disease.
      Adult patients with a cerebral blood volume increase may be at high risk for
      radiological and symptomatic hyperperfusion after surgery. Careful perioperative
      management would reduce surgical complications and improve long-term outcome in
      moyamoya disease.

PMID- 22871685
TI  - Tracking down atrial fibrillation in the stroke unit.

PMID- 22871686
TI  - A contusive model of unilateral cervical spinal cord injury using the infinite
      horizon impactor.
AB  - While the majority of human spinal cord injuries occur in the cervical spinal
      cord, the vast majority of laboratory research employs animal models of spinal
      cord injury (SCI) in which the thoracic spinal cord is injured. Additionally,
      because most human cord injuries occur as the result of blunt, non-penetrating
      trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is
      violently struck by displaced bone or soft tissues, the majority of SCI
      researchers are of the opinion that the most clinically relevant injury models
      are those in which the spinal cord is rapidly contused.(1) Therefore, an
      important step in the preclinical evaluation of novel treatments on their way to
      human translation is an assessment of their efficacy in a model of contusion SCI
      within the cervical spinal cord. Here, we describe the technical aspects and
      resultant anatomical and behavioral outcomes of an unilateral contusive model of
      cervical SCI that employs the Infinite Horizon spinal cord injury impactor.
      Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To
      optimize the reproducibility of the biomechanical, functional, and histological
      outcomes of the injury model, we contused the spinal cords using an impact force
      of 150 kdyn, an impact trajectory of 22.5 degrees  (animals rotated at 22.5
      degrees ), and an impact location off of midline of 1.4 mm. Functional recovery
      was assessed using the cylinder rearing test, horizontal ladder test, grooming
      test and modified Montoya's staircase test for up to 6 weeks, after which the
      spinal cords were evaluated histologically for white and grey matter sparing. The
      injury model presented here imparts consistent and reproducible biomechanical
      forces to the spinal cord, an important feature of any experimental SCI model.
      This results in discrete histological damage to the lateral half of the spinal
      cord which is largely contained to the ipsilateral side of injury. The injury is
      well tolerated by the animals, but does result in functional deficits of the
      forelimb that are significant and sustained in the weeks following injury. The
      cervical unilateral injury model presented here may be a resource to researchers
      who wish to evaluate potentially promising therapies prior to human translation.

PMID- 22871687
TI  - Modeling the latent dimensions of multivariate signaling datasets.
AB  - Cellular signal transduction is coordinated by modifications of many proteins
      within cells. Protein modifications are not independent, because some are
      connected through shared signaling cascades and others jointly converge upon
      common cellular functions. This coupling creates a hidden structure within a
      signaling network that can point to higher level organizing principles of
      interest to systems biology. One can identify important covariations within large
      scale datasets by using mathematical models that extract latent dimensions-the
      key structural elements of a measurement set. In this paper, we introduce two
      principal component-based methods for identifying and interpreting latent
      dimensions. Principal component analysis provides a starting point for unbiased
      inspection of the major sources of variation within a dataset. Partial least
      squares regression reorients these dimensions toward a specific hypothesis of
      interest. Both approaches have been used widely in studies of cell signaling, and
      they should be standard analytical tools once highly multivariate datasets become
      straightforward to accumulate.

PMID- 22871688
TI  - Examining the role of nasopharyngeal-associated lymphoreticular tissue (NALT) in
      mouse responses to vaccines.
AB  - The nasopharyngeal-associated lymphoreticular tissues (NALT) found in humans,
      rodents, and other mammals, contribute to immunity in the nasal sinuses(1-3). The
      NALT are two parallel bell-shaped structures located in the nasal passages above
      the hard palate, and are usually considered to be secondary components of the
      mucosal-associated lymphoid system(4-6). Located within the NALT are discrete
      compartments of B and T lymphocytes interspersed with antigen-presenting
      dendritic cells(4,7,8). These cells are surrounded by an epithelial cell layer
      intercalated with M-cells that are responsible for antigen retrieval from the
      mucosal surfaces of the air passages(9,10). Naive lymphocytes circulating through
      the NALT are poised to respond to first encounters with respiratory pathogens(7).
      While NALT disappear in humans by the age of two years, the Waldeyer's Ring and
      similarly structured lymphatic organs continue to persist throughout life(6). In
      contrast to humans, mice retain NALT throughout life, thus providing a convenient
      animal model for the study of immune responses originating within the nasal
      sinuses(11). Cultures of single-cell suspensions of NALT are not practical due to
      low yields of mononuclear cells. However, NALT biology can be examined by ex vivo
      culturing of the intact organ, and this method has the additional advantage of
      maintaining the natural tissue structure. For in vivo studies, genetic knockout
      models presenting defects limited to NALT are not currently available due to a
      poor understanding of the developmental pathway. For example, while lymphotoxin
      alpha knockout mice have atrophied NALT, the Peyer's patches, peripheral lymph
      nodes, follicular dendritic cells and other lymphoid tissues are also altered in
      these genetically manipulated mice(12,13). As an alternative to gene knockout
      mice, surgical ablation permanently eliminates NALT from the nasal passage
      without affecting other tissues. The resulting mouse model has been used to
      establish relationships between NALT and immune responses to vaccines(1,3).
      Serial collection of serum, saliva, nasal washes and vaginal secretions is
      necessary for establishing the basis of host responses to vaccination, while
      immune responses originating directly from NALT can be confirmed by tissue
      culture. The following procedures outline the surgeries, tissue culture and
      sample collection necessary to examine local and systemic humoral immune
      responses to intranasal (IN) vaccination.

PMID- 22871689
TI  - Surface Andreev bound states of superfluid 3He and Majorana fermions.
AB  - Superfluid (3)He is an intensively investigated and well characterized p-wave
      superfluid. In the bulk Balian-Werthamer state, which is commonly called the
      (3)He B phase, the superfluid gap is opened  isotropically but near a flat
      boundary such as a wall of a container it can harbor interesting quasi-particle
      states inside the gap. These states are called surface Andreev bound states, and
      have not been experimentally explored in detail. Transverse acoustic impedance
      measurement has revealed their existence and provided spectroscopic details of
      the dispersion of the bound states. Recent theoretical arguments claim that the
      surface Andreev bound states of the superfluid (3)He B phase can be recognized as
      the edge states of the topological superfluid and be regarded as a Majorana
      fermion, a fancy particle which has not been confirmed in elementary particle
      physics. In this review, we present up-to-date knowledge on the surface Andreev
      bound states of the (3)He B phase revealed by acoustic spectroscopy and the
      possible realization of a Majorana fermion, along with related studies on this
      topic.

PMID- 22871690
TI  - Can biotech spur job creation?

PMID- 22871691
TI  - Shire punts on bioscaffolds for cell-based regenerative medicine.

PMID- 22871693
TI  - Cautious optimism surrounds early clinical data for PD-1 blocker.

PMID- 22871696
TI  - Genentech's Alzheimer's antibody trial to study disease prevention.

PMID- 22871697
TI  - Rare-disease drugs boosted by new Prescription Drug User Fee Act.

PMID- 22871701
TI  - Incentives aim to boost antibiotic development.

PMID- 22871702
TI  - Destruction of transgenic olive field trial dubbed 'vandalism'.

PMID- 22871703
TI  - Investors boost Canadian startups but public sector underperforms.

PMID- 22871704
TI  - Biotech weathers 2Q12 slump.

PMID- 22871705
TI  - Adult stem cell therapies walk the line.

PMID- 22871706
TI  - It's the problem, stupid!

PMID- 22871707
TI  - In support of the European Union biosimilar framework.

PMID- 22871709
TI  - Silos hamstring Chinese plant biotech sector.

PMID- 22871710
TI  - Public biotech 2011--the numbers.

PMID- 22871711
TI  - Stealing fire: a retrospective survey of biotech patent claims in the wake of
      Mayo v. Prometheus.

PMID- 22871713
TI  - Channeling DNA for optical mapping.

PMID- 22871714
TI  - Transcriptome sequencing of single cells with Smart-Seq.

PMID- 22871715
TI  - The tomato genome fleshed out.

PMID- 22871721
TI  - Eric Schadt. Interview by H. Craig Mak.

PMID- 22871722
TI  - Second-quarter biotech job picture.

PMID- 22871726
TI  - Nanoplasmonic detection of adenosine triphosphate by aptamer regulated self
      catalytic growth of single gold nanoparticles.
AB  - We present a nanoplasmonic aptasensor for adenosine triphosphate (ATP) by using
      single gold nanoparticles (GNPs) as probes. The specific aptamer-ATP binding
      induced conformational change could modulate the surface-dependent self-catalytic
      growth of GNPs, which enabled the detection of ATP with ultra-sensitivity and
      selectivity.

PMID- 22871727
TI  - Manipulation of single polymerase-DNA complexes: a mechanical view of DNA
      unwinding during replication.

PMID- 22871728
TI  - Drosophila growth and development: keeping things in proportion.

PMID- 22871729
TI  - IF1 reprograms energy metabolism and signals the oncogenic phenotype in cancer.

PMID- 22871730
TI  - T-ARG-eting E2F-1 growth control.

PMID- 22871731
TI  - A long way to stemness.

PMID- 22871732
TI  - Through the looking-glass: observing HSCs through the lens of infection reveals
      unexpected insights into HSC function.

PMID- 22871733
TI  - pH neutralization protects against reduction in replicative lifespan following
      chronological aging in yeast.
AB  - Chronological and replicative aging have been studied in yeast as alternative
      paradigms for post-mitotic and mitotic aging, respectively. It has been known for
      more than a decade that cells of the S288C background aged chronologically in
      rich medium have reduced replicative lifespan relative to chronologically young
      cells. Here we report replication of this observation in the diploid BY4743
      strain background. We further show that the reduction in replicative lifespan
      from chronological aging is accelerated when cells are chronologically aged under
      standard conditions in synthetic complete medium rather than rich medium. The
      loss of replicative potential with chronological age is attenuated by buffering
      the pH of the chronological aging medium to 6.0, an intervention that we have
      previously shown can extend chronological lifespan. These data demonstrate that
      extracellular acidification of the culture medium can cause intracellular damage
      in the chronologically aging population that is asymmetrically segregated by the
      mother cell to limit subsequent replicative lifespan.

PMID- 22871735
TI  - Persistent DNA damage caused by low levels of mitomycin C induces irreversible
      cell senescence.
AB  - Mutations of oncogenes and tumor suppressor genes which activate mTOR through
      several downstream signaling pathways are common to cancer. Activation of mTOR
      when combined with inhibition of cell cycle progression or DNA replication stress
      has previously been shown to promote cell senescence. In the present study, we
      examined the conditions under which human non-small cell lung carcinoma A549
      cells can undergo senescence when treated with the DNA alkylating agent mitomycin
      C (MMC). While exposure of A549 cells to 0.1 or 0.5 ug/ml of MMC led to their
      arrest in S phase of the cell cycle and subsequent apoptosis, exposure to 0.01 or
      0.02 ug/ml for 6 d resulted in induction of cell senescence and near total (0.01
      ug/ml) or total (0.02 ug/ml) elimination of their reproductive potential. During
      exposure to these low concentrations of MMC, the cells demonstrated evidence of
      DNA replication stress manifested by expression of gammaH2AX, p21 (WAF1)  and a
      very low level of EdU incorporation into DNA. The data are consistent with the
      notion that enduring DNA replication stress in cells known to have activated
      oncogenes leads to their senescence. It is reasonable to expect that tumors
      having constitutive activation of oncogenes triggering mTOR signaling may be
      particularly predisposed to undergoing senescence following prolonged treatment
      with low doses of DNA damaging drugs.

PMID- 22871734
TI  - Werner syndrome protein suppresses the formation of large deletions during the
      replication of human telomeric sequences.
AB  - Werner syndrome (WS) is a disorder characterized by features of premature aging
      and increased cancer that is caused by loss of the RecQ helicase WRN. Telomeres
      consisting of duplex TTAGGG repeats in humans protect chromosome ends and sustain
      cellular proliferation. WRN prevents the loss of telomeres replicated from the G
      rich strand, which can form secondary G-quadruplex (G4) structures. Here, we
      dissected WRN roles in the replication of telomeric sequences by examining
      factors inherent to telomeric repeats, such as G4 DNA, independently from other
      factors at chromosome ends that can also impede replication. For this we used the
      supF shuttle vector (SV) mutagenesis assay. We demonstrate that SVs with
      [TTAGGG]6 sequences are stably replicated in human cells, and that the repeats
      suppress the frequency of large deletions despite G4 folding potential. WRN
      depletion increased the supF mutant frequency for both the telomeric and non
      telomeric SVs, compared with the control cells, but this increase was much
      greater (27-fold) for telomeric SVs. The higher SV mutant frequencies in WRN
      deficient cells were primarily due to an increase in large sequence deletions and
      rearrangements. However, WRN depletion caused a more dramatic increase in
      deletions and rearrangements arising within the telomeric SV (70-fold), compared
      with non-telomeric SV (8-fold). Our results indicate that WRN prevents large
      deletions and rearrangements during replication, and that this role is
      particularly important in templates with telomeric sequence. This provides a
      possible explanation for increased telomere loss in WS cells.

PMID- 22871736
TI  - CDK1 differentially regulates G-overhang generation at leading- and lagging
      strand telomeres in telomerase-negative cells in G2 phase.
AB  - Human telomeres contain single-stranded 3' G-overhangs that function in telomere
      end protection and telomerase action. Previously we have demonstrated that
      multiple steps involving C-strand end resection, telomerase elongation and C
      strand fill-in contribute to G-overhang generation in telomerase-positive cancer
      cells. However, how G-overhangs are generated in telomerase-negative human
      somatic cells is unknown. Here, we report that C-strand fill-in is present at
      lagging-strand telomeres in telomerase-negative human cells but not at leading
      strand telomeres, suggesting that C-strand fill-in is independent of telomerase
      extension of G-strand. We further show that while cyclin-dependent kinase 1
      (CDK1) positively regulates C-strand fill-in, CDK1 unlikely regulates G-overhang
      generation at leading-strand telomeres. In addition, DNA polymerase alpha
      (Polalpha) association with telomeres is not altered upon CDK1 inhibition,
      suggesting that CDK1 does not control the loading of Polalpha to telomeres during
      fill-in. In summary, our results reveal that G-overhang generation at leading-
      and lagging-strand telomeres are regulated by distinct mechanisms in human cells.

PMID- 22871737
TI  - Lack of response to unaligned chromosomes in mammalian female gametes.
AB  - Chromosome segregation errors are highly frequent in mammalian female meiosis,
      and their incidence gradually increases with maternal age. The fate of aneuploid
      eggs is obviously dependent on the stringency of mechanisms for detecting
      unattached or repairing incorrectly attached kinetochores. In case of their
      failure, the newly formed embryo will inherit the impaired set of chromosomes,
      which will have severe consequences for its further development. Whether spindle
      assembly checkpoint (SAC) in oocytes is capable of arresting cell cycle
      progression in response to unaligned kinetochores was discussed for a long time.
      It is known that abolishing SAC increases frequency of chromosome segregation
      errors and causes precocious entry into anaphase; SAC, therefore, seems to be
      essential for normal chromosome segregation in meiosis I. However, it was also
      reported that for anaphase-promoting complex (APC) activation, which is a
      prerequisite for entering anaphase; alignment of only a critical mass of
      kinetochores on equatorial plane is sufficient. This indicates that the function
      of SAC and of cooperating chromosome attachment correction mechanisms in oocytes
      is different from somatic cells. To analyze this phenomenon, we used live cell
      confocal microscopy to monitor chromosome movements, spindle formation, APC
      activation and polar body extrusion (PBE) simultaneously in individual oocytes at
      various time points during first meiotic division. Our results, using oocytes
      from aged animals and interspecific crosses, demonstrate that multiple unaligned
      kinetochores and severe congression defects are tolerated at the metaphase to
      anaphase transition, although such cells retain sensitivity to nocodazole. This
      indicates that checkpoint mechanisms, operating in oocytes at this point, are
      essential for accurate timing of APC activation in meiosis I, but they are
      insufficient in detection or correction of unaligned chromosomes, preparing thus
      conditions for propagation of the aneuploidy to the embryo.

PMID- 22871738
TI  - The MEN mediates the effects of the spindle assembly checkpoint on Kar9-dependent
      spindle pole body inheritance in budding yeast.
AB  - Many asymmetrically dividing cells segregate the poles of the mitotic spindle non
      randomly between their two daughters. In budding yeast, the protein Kar9
      localizes almost exclusively to the astral microtubules emanating from the old
      spindle pole body (SPB) and promotes its movement toward the bud. Thereby, Kar9
      orients the spindle relative to the division axis. Here, we show that beyond
      perturbing Kar9 distribution, activation of the spindle assembly checkpoint (SAC)
      randomizes SPB inheritance. Inactivation of the B-type cyclin Clb5 led to a SAC
      dependent defect in Kar9 orientation and SPB segregation. Furthermore, unlike the
      Clb4-dependent pathway, the Clb5- and SAC-dependent pathways functioned
      genetically upstream of the mitotic exit network (MEN) in SPB specification and
      Kar9-dependent SPB inheritance. Together, our study indicates that Clb5 functions
      in spindle assembly and that the SAC controls the specification and inheritance
      of yeast SPBs through inhibition of the MEN.

PMID- 22871739
TI  - E2F1 confers anticancer drug resistance by targeting ABC transporter family
      members and Bcl-2 via the p73/DNp73-miR-205 circuitry.
AB  - Resistance to anti-neoplastic agents is the major cause of therapy failure,
      leading to disease recurrence and metastasis. E2F1 is a strong inducer of
      apoptosis in response to DNA damage through its capacity to activate p53/p73
      death pathways. Recent evidence, however, showed that E2F1, which is aberrantly
      expressed in advanced malignant melanomas together with antagonistic p73 family
      members, drives cancer progression. Investigating mechanisms responsible for
      dysregulated E2F1 losing its apoptotic function, we searched for genomic
      signatures in primary and late clinical tumor stages to allow the prediction of
      downstream effectors associated with apoptosis resistance and survival of
      aggressive melanoma cells. We identified miR-205 as specific target of p73 and
      found that upon genotoxic stress, its expression is sufficiently abrogated by
      endogenous DNp73. Significantly, metastatic cells can be rescued from drug
      resistance by selective knockdown of DNp73 or overexpression of miR-205 in p73
      depleted cells, leading to increased apoptosis and the reduction of tumor growth
      in vivo. Our data delineate an autoregulatory circuit, involving high levels of
      E2F1 and DNp73 to downregulate miR-205, which, in turn, controls E2F1
      accumulation. Finally, drug resistance associated to this genetic signature is
      mediated by removing the inhibitory effect of miR-205 on the expression of Bcl-2
      and the ATP-binding cassette transporters A2 (ABCA2) and A5 (ABCA5) related to
      multi-drug resistance and malignant progression. These results define the E2F1
      p73/DNp73-miR-205 axis as a crucial mechanism for chemoresistance and, thus, as a
      target for metastasis prevention.

PMID- 22871740
TI  - Low-dose laulimalide represents a novel molecular probe for investigating
      microtubule organization.
AB  - Laulimalide is a natural product that has strong taxoid-like properties but binds
      to a distinct site on beta-tubulin in the microtubule (MT) lattice. At elevated
      concentrations, it generates MTs that are resistant to depolymerization, and it
      induces a conformational state indistinguishable from taxoid-treated MTs. In this
      study, we describe the effect of low-dose laulimalide on various stages of the
      cell cycle and compare these effects to docetaxel as a representative of taxoid
      stabilizers. No evidence of MT bundling in interphase was observed with
      laulimalide, in spite of the fact that MTs are stabilized at low dose. Cells
      treated with laulimalide enter mitosis but arrest at prometaphase by generating
      multiple asters that coalesce into supernumerary poles and interfere with the
      integrity of the metaphase plate. Cells with a preformed bipolar spindle exist
      under heightened tension under laulimalide treatment, and chromosomes rapidly
      shear from the plate, even though the bipolar spindle is well-preserved.
      Docetaxel generates a similar phenotype for HeLa cells entering mitosis, but when
      treated at metaphase, cells undergo chromosomal fragmentation and demonstrate
      reduced centromere dynamics, as expected for a taxoid. Our results suggest that
      laulimalide represents a new class of molecular probe for investigating MT
      mediated events, such as kinetochore-MT interactions, which may reflect the
      location of the ligand binding site within the interprotofilament groove.

PMID- 22871741
TI  - An anti-let-7 sponge decoys and decays endogenous let-7 functions.
AB  - The let-7 family contains 12 members, which share identical seed regions,
      suggesting that they may target the same mRNAs. It is essential to develop a
      means that can regulate the functions of all members. Using a DNA synthesis
      technique, we have generated an anti-let-7 sponge aiming to modulate the function
      of all members. We found that products of the anti-let-7 construct could bind and
      inactivate all members of the let-7 family, producing decoy and decay effects. To
      test the role of the anti-let-7 sponge, we stably expressed the anti-let-7
      construct in two types of cells, the breast carcinoma cells MT-1 and the oldest
      and most commonly used human cervical cancer cell line, HeLa cells. We found that
      expression of anti-let-7 increased cell survival, invasion and adhesion, which
      corroborate with known functions of let-7 family members. We further identified a
      novel target site across all species of the let-7 family in hyaluronan synthase 2
      (HAS2). HAS2 overexpression produced similar effects as the anti-let-7 sponge.
      Silencing HAS2 expression by siRNAs produced opposite effects to anti-let-7 on
      cell survival and invasion. The ability of anti-let-7 to regulate multiple
      members of the let-7 family allows us to observe their multiple functions using a
      single reagent. This approach can be applied to other family members with
      conserved sequences.

PMID- 22871743
TI  - "Overpass" at the junction of a crossed microchannel: an enabler for 3D
      microfluidic chips.
AB  - Reported here is the design and fabrication of three-dimensional (3D) "overpass"
      microstructures at the junction of crossed microfluidic channels by femtosecond
      laser direct writing of photopolymers. The post-integrated overpass could be used
      for guiding different microfluids across the junction without mixing; therefore
      it is proposed as an enabler for achieving 3D microfluidic chips based on
      conventional two-dimensional (2D) microchannels. As representative examples, bi
      crossed and tri-crossed microchannels have been equipped with bi-connected and
      tri-connected overpasses, respectively. Flow tests confirm 3D flowing capability.
      The integration of such overpass structures at the microchannel junction provides
      an opportunity to impart 3D capability to conventional 2D microchips, thus the
      method may hold great promise for both functionalization and miniaturization of
      Lab-on-a-Chip systems.

PMID- 22871742
TI  - CDC6 expression is regulated by lineage-specific transcription factor GATA1.
AB  - GATA1 is a hematopoietic transcription factor essential for expression of most
      genes encoding erythro-megakaryocytic proteins, i.e., globins and platelet
      glycoproteins. A role for GATA1 as a cell proliferation regulator has been
      proposed, as some of its bona fide targets comprise global regulators, such as c
      KIT or c-MYC, or cell cycle factors, i.e., CYCLIN D or p21CIP1. In this study, we
      describe that GATA1 directly regulates the expression of replication licensing
      factor CDC6. Using reporter transactivation, electrophoretic mobility shift and
      chromatin immunoprecipitation assays, we show that GATA1 stimulates CDC6
      transcription by binding to a canonical binding site located within a 166bp
      enhancer region upstream CDC6 promoter. This evolutionary conserved GATA binding
      site conforms to recently described chromatin occupancy rules, i.e., preferred
      bases within core WGATAR (TGATAA), 5' and 3' flanking bases (GGTGATAAGG) and
      distance to the transcription initiation site. We also found adjacent conserved
      binding sites for ubiquitously expressed transcription factor CP2, needed for
      GATA activity on CDC6 enhancer. Our results add to the growing evidence for GATA1
      acting as a direct transcriptional regulator of the cell cycle machinery, thus
      linking cell proliferation control and specific gene expression programs during
      lineage differentiation.

PMID- 22871744
TI  - Current treatment strategies in Hodgkin lymphomas.
AB  - PURPOSE OF REVIEW: This review will focus on monoclonal antibodies and small
      molecule inhibitors used in the treatment of newly diagnosed and
      relapsed/refractory classical Hodgkin lymphoma. RECENT FINDINGS: Development of
      novel therapies is highly needed to improve treatment outcome of relapsed
      patients. New agents have shown to be effective and safe suggesting their use in
      combination with conventional therapy or with other targeted therapies in
      frontline and salvage regimens. SUMMARY: Approximately 9000 new cases of Hodgkin
      lymphoma will be diagnosed in 2012, representing 11% of all lymphomas in the USA.
      Although considered a highly curable malignancy, a third of patients will not
      respond to or relapse after initial therapy. Second-line therapy typically
      includes multiagent chemotherapy regimens followed by autologous stem cell
      transplantation. Patients whose disease relapses after autologous stem cell
      transplantation have poor prognosis, with a median survival of less than 3 years.

PMID- 22871745
TI  - Drug safety in COPD revisited: what is the number needed to analyze?

PMID- 22871746
TI  - Know your ventilator to beat the leak.

PMID- 22871747
TI  - Bronchoscopy for the solitary pulmonary nodule: friend or foe?

PMID- 22871748
TI  - Can we predict who will develop chronic sequelae of acute inhalational injury?

PMID- 22871750
TI  - Point: should benzodiazepines be avoided in mechanically ventilated patients?
      Yes.

PMID- 22871751
TI  - Counterpoint: should benzodiazepines be avoided in mechanically ventilated
      patients? No.

PMID- 22871754
TI  - Patient-reported outcomes in idiopathic pulmonary fibrosis research.
AB  - Patient-reported outcomes (PROs) include questionnaires or surveys that ask
      patients for their perceptions about things like symptoms they are experiencing
      or quality of life. For incurable, morbid, life-shortening conditions like
      idiopathic pulmonary fibrosis (IPF), PROs are particularly germane: They
      elucidate for clinicians and researchers what it is like for patients to live
      with such a disease, and they may detect important treatment effects not captured
      by other metrics (eg, pulmonary physiology). However, a relative paucity of
      research on PROs in IPF has left significant knowledge gaps in this area and
      contributed to the timidity investigators have about using PROs as prominent
      outcomes in IPF drug trials. Additional research on existing instruments is
      needed to establish or bolster their basic psychometric properties in IPF. When
      PROs are used as end points in therapeutic trials, analyzing PRO response data
      can be challenging, but these challenges can be overcome with a transparent,
      thoughtful, and sophisticated statistical approach. In this article, we discuss
      some of the basics of PRO assessment, existing knowledge gaps in IPF-related PRO
      research, and the potential usefulness of using PROs in IPF trials and conclude
      by offering specific recommendations for an approach to analyzing repeated
      measures PRO data from IPF trials.

PMID- 22871755
TI  - Bronchodilator use and the risk of arrhythmia in COPD: part 1: Saskatchewan
      cohort study.
AB  - BACKGROUND: Bronchodilators are first-line therapy for COPD. There is some
      evidence that they may increase the risk of cardiac arrhythmias. METHODS: We used
      the computerized health-care databases of the Province of Saskatchewan, Canada,
      to identify a cohort of subjects with COPD, aged >= 55 years, between 1990 and
      1999. The subjects were followed until December 2003 for a hospital admission
      for, or death from, arrhythmia. A nested case-control approach was used to match
      each arrhythmia case on age, sex, and calendar time to 20 control subjects
      selected from the corresponding cohort risk set. Conditional logistic regression
      was used to estimate the rate ratio (RR) of arrhythmia associated with new use of
      bronchodilators, adjusted for disease severity and comorbidity. RESULTS: The
      cohort included 6,018 patients with COPD in whom 469 arrhythmia cases occurred,
      including 56 deaths, for an overall rate of 1.37 arrhythmias per 100 per year.
      The rate of arrhythmia was elevated with the new use of ipratropium (RR, 2.4; 95%
      CI, 1.4-4.0) and of long-acting beta-agonists (LABAs) (RR, 4.5; 95% CI, 1.4
      14.4). It was not elevated with new use of short-acting beta-agonists (RR, 0.9;
      95% CI, 0.5-1.6) or methylxanthines (RR, 1.6; 95% CI, 0.7-3.7). CONCLUSIONS: The
      new use of bronchodilators, particularly ipratropium and LABAs, may increase the
      risk of cardiac arrhythmias in patients with COPD. Although these results raise
      concerns regarding LABAs, they were based on few cases and require confirmation
      in larger cohorts.

PMID- 22871756
TI  - Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in
      the larger Quebec cohort.
AB  - BACKGROUND: A previous study suggested a potential increased risk of cardiac
      arrhythmia with new use of long-acting beta-agonists and ipratropium bromide in
      patients with COPD, although conclusions were limited by the small cohort size.
      METHODS: We reassessed this association in a larger cohort formed from the health
      care databases of the province of Quebec, Canada. We identified a cohort of
      patients with COPD aged >= 67 years who began treatment between 1990 and 1999 and
      followed them until December 2003. A nested case-control approach matched each
      subject who developed severe arrhythmia during follow-up with 20 control subjects
      from the cohort on age, sex, and calendar time. The rate ratio (RR) of arrhythmia
      associated with new use of bronchodilators was estimated using conditional
      logistic regression, adjusting for COPD disease severity, cardiovascular disease,
      and other comorbidities. RESULTS: The cohort included 76,661 patients with COPD,
      of whom 5,307 developed an arrhythmia (10.3 arrhythmias per 1,000 per year), 621
      of which were fatal. The rate of cardiac arrhythmias was elevated with the new
      use of short-acting (RR, 1.27; 95% CI, 1.03-1.57) and long-acting (RR, 1.47; 95%
      CI, 1.01-2.15) beta-agonists. The rate was slightly elevated, although not
      statistically significantly, with new use of ipratropium bromide (RR, 1.23; 95%
      CI, 0.95-1.57) and methylxanthines (RR, 1.28; 95% CI, 0.93-1.77). These effects
      waned with longer-term use. CONCLUSIONS: New use of short- and long-acting beta
      agonists may slightly increase the risk of cardiac arrhythmia in patients with
      COPD. It remains unclear whether ipratropium bromide also increases this risk,
      despite the use of a larger study population.

PMID- 22871757
TI  - Cysteinyl leukotriene 1 receptor expression associated with bronchial
      inflammation in severe exacerbations of COPD.
AB  - BACKGROUND: Cysteinyl leukotriene 1 (CysLT1) receptor expression is known to be
      increased in the airway mucosa of patients with asthma, especially during
      exacerbations; however, nothing is known of its expression in COPD. METHODS: We
      applied immunohistochemistry and in situ hybridization to endobronchial biopsies
      to determine inflammatory cell CysLT1 receptor protein and mRNA expression in the
      following: (1) 15 nonsmoker control subjects (NSC), (2) 16 smokers with moderate
      to severe COPD in its stable phase (S-COPD), and (3) 15 smokers with COPD
      hospitalized for a severe exacerbation (SE-COPD). RESULTS: The total number of
      bronchial mucosal inflammatory cells (CD45+) and those expressing CysLT1 receptor
      protein were significantly greater in SE-COPD (CysLT1 receptor protein: median
      [range] = 139 [31-634]) as compared with S-COPD (32 [6-114]) or NSC (16 [4-66])
      (P < .001 for both). CysLT1 receptor gene expression showed similar differences.
      A greater proportion of CD451 cells expressed CysLT1 receptor protein in SE-COPD
      (median [range] = 22% [8-81]) compared with S-COPD (10% [4-32]) (P < .03) or NSC
      (7% [1-19]) (P < .002). In SE-COPD, the relative frequencies of CysLT1 receptor
      expressing cells were as follows: tryptase1 mast cells > CD681
      monocytes/macrophage > neutrophils > CD201 B lymphocytes = EG21 eosinophils.
      Moreover, there were positive correlations between the numbers of cells
      expressing CysLT1 receptor protein and the numbers of CD451 cells (r = 0.78; P <
      .003) and tryptase1 mast cells (r = 0.62; P < .02). CONCLUSIONS: Bronchial
      mucosal CysLT1 receptor-positive inflammatory cells are present in the bronchial
      mucosa in COPD in greatest number in those experiencing a severe exacerbation.

PMID- 22871758
TI  - Pneumococcal pneumonia: mechanisms of infection and resolution.
AB  - Vaccination and antimicrobial therapy remain the cornerstones of the management
      of pneumococcal pneumonia. Despite significant successes, the capacity of the
      pneumococcus to evolve in the face of the selective pressure of anticapsular
      immunity challenges immunization programs. Treatment focuses on antimicrobial
      therapy but ignores the central role of the dysregulated inflammatory response
      during pneumonia. Future therapeutic approaches need to build on the considerable
      recent advances in our understanding of the pathogenesis of pneumococcal
      pneumonia, including those from models of pneumonia. Enhancement of the essential
      components of the host response that prevents most colonized individuals from
      developing pneumonia and strategies to limit inappropriate inflammatory responses
      to lower respiratory tract infection are approaches that could be exploited to
      improve disease outcome. This review highlights recent discoveries relating to
      the microbial and host determinants of microbial clearance and regulation of the
      inflammatory response, which provide clues as to how this could be achieved in
      the future.

PMID- 22871759
TI  - Respiratory manifestations of malaria.
AB  - Respiratory distress develops in up to 25% of adults and 40% of children with
      severe falciparum malaria. Its diverse causes include respiratory compensation of
      metabolic acidosis, noncardiogenic pulmonary edema, concomitant pneumonia, and
      severe anemia. Patients with severe falciparum, vivax, and knowlesi malaria may
      develop acute lung injury (ALI) and ARDS, often several days after antimalarial
      drug treatment. ARDS rates, best characterized for severe Plasmodium falciparum,
      are 5% to 25% in adults and up to 29% in pregnant women; ARDS is rare in young
      children. ARDS pathophysiology centers on inflammatory-mediated increased
      capillary permeability or endothelial damage leading to diffuse alveolar damage
      that can continue after parasite clearance. The role of parasite sequestration in
      the pulmonary microvasculature is unclear, because sequestration occurs intensely
      in P falciparum, less so in P knowlesi, and has not been shown convincingly in P
      vivax. Because early markers of ALI/ARDS are lacking, fluid resuscitation in
      severe malaria should follow the old adage to "keep them dry." Bacteremia and
      hospital-acquired pneumonia can complicate severe malaria and may contribute to
      ALI/ARDS. Mechanical ventilation can save life in ALI/ARDS. Basic critical care
      facilities are increasingly available in tropical countries. The use of lung
      protective ventilation has helped to reduce mortality from malaria-induced
      ALI/ARDS, but permissive hypercapnia in unconscious patients is not recommended
      because increased intracranial pressure and cerebral swelling may occur in
      cerebral malaria. The best antimalarial treatment of severe malaria is IV
      artesunate.

PMID- 22871760
TI  - Lung volumes: measurement, clinical use, and coding.
AB  - Measurement of lung volumes is an integral part of complete pulmonary function
      testing. Some lung volumes can be measured during spirometry; however,
      measurement of the residual volume (RV), functional residual capacity (FRC), and
      total lung capacity (TLC) requires special techniques. FRC is typically measured
      by one of three methods. Body plethysmography uses Boyle's Law to determine lung
      volumes, whereas inert gas dilution and nitrogen washout use dilution properties
      of gases. After determination of FRC, expiratory reserve volume and inspiratory
      vital capacity are measured, which allows the calculation of the RV and TLC. Lung
      volumes are commonly used for the diagnosis of restriction. In obstructive lung
      disease, they are used to assess for hyperinflation. Changes in lung volumes can
      also be seen in a number of other clinical conditions. Reimbursement for
      measurement of lung volumes requires knowledge of current procedural terminology
      (CPT) codes, relevant indications, and an appropriate level of physician
      supervision. Because of recent efforts to eliminate payment inefficiencies, the
      10 previous CPT codes for lung volumes, airway resistance, and diffusing capacity
      have been bundled into four new CPT codes.

PMID- 22871761
TI  - Severe endobronchitis and airway stricture caused by inhalation of cosmetic talc.
AB  - Pulmonary disease caused by talc is well described, but previous reports mainly
      describe lung parenchymal involvement. We describe what is, to our knowledge, the
      first case in which inhalation of cosmetic talc led to intense endobronchitis and
      airway stricture. A 70-year-old woman presented with new-onset wheezing and was
      found to have right upper lobe collapse on chest radiography. CT imaging of the
      thorax showed right upper lobe collapse with occlusion of the right upper lobe.
      Bronchoscopy showed severe endobronchitis with thickened mucosa throughout the
      right and left main stem bronchi and a fibrotic stricture occluding the right
      upper lobe. Bronchial biopsy specimens showed foreign-body granulomatosis
      encasing birefringent crystalline material. Spectral analysis confirmed the
      crystals to be consistent with cosmetic talc used by the patient. We hypothesize
      that the patient inhaled a large amount of talc, which was trapped in the larger
      airways and resulted in intense foreign-body granulomatosis, leading to an airway
      stricture.

PMID- 22871762
TI  - Omalizumab as a steroid-sparing agent in chronic eosinophilic pneumonia.
AB  - Chronic eosinophilic pneumonia (CEP) is an idiopathic eosinophilic pulmonary
      disease characterized by an abnormal and marked accumulation of eosinophils in
      the lung. Common presenting complaints include cough, fever, dyspnea, wheezing,
      and night sweats. Common laboratory abnormalities are peripheral blood and BAL
      eosinophilia. The pathognomonic radiographic finding is bilateral peripheral
      infiltrates. Corticosteroids are the mainstay of therapy, and dramatic
      improvement follows treatment. Relapses are common, and most patients require
      prolonged therapy. Side effects associated with chronic corticosteroid therapy
      must be monitored. Our case was that of a 36-year-old woman who had
      characteristic clinical and radiologic features. She was treated with
      corticosteroids but she needed prolonged therapy, and side effects occurred.
      Because the patient had high IgE levels and a positive skin prick test result, we
      used omalizumab for the treatment. The patient responded well. To our knowledge,
      this is the first CEP case in the literature successfully treated with
      omalizumab.

PMID- 22871763
TI  - The appearance of central sleep apnea after treatment of obstructive sleep apnea.
AB  - Patients with a primary diagnosis of obstructive sleep apnea frequently
      demonstrate central sleep apnea that emerges during treatment with CPAP. Although
      a number of mechanisms for this finding have been hypothesized, the
      pathophysiology is not definitively known. Controversy exists as to whether the
      concomitant appearance of the two phenomena represents a distinct meaningful
      entity. Regardless, the coincidence of these diseases may have important clinical
      implications. Herein, we review the proposed mechanisms for obstructive sleep
      apnea complicated by central sleep apnea. Future research is needed to elucidate
      the relative importance and susceptibility to intervention of the various
      pathophysiologic mechanisms responsible for this phenomenon, and whether a
      treatment approach distinct from that of pure obstructive apnea is justified.

PMID- 22871764
TI  - A 77-year-old woman with dyspnea and cardiac mass.

PMID- 22871765
TI  - A 47-year-old woman with worsening dyspnea, arthritis, and muscle pain.

PMID- 22871766
TI  - Dyspnea and hypoxia in a 64-year-old male traveler.

PMID- 22871771
TI  - Ultrasonography for the detection of pneumothorax.

PMID- 22871773
TI  - A closer look at the value proposition for endobronchial ultrasound.

PMID- 22871775
TI  - Obesity hypoventilation syndrome: the need for a multifaceted approach to
      treatment.

PMID- 22871777
TI  - Concerns raised by lung size-mismatched transplantation.

PMID- 22871779
TI  - Ciliary beat pattern analysis below 37 degrees C may increase risk of primary
      ciliary dyskinesia misdiagnosis.

PMID- 22871781
TI  - Screening for antiphospholipid antibodies in women with pregnancy complications.

PMID- 22871783
TI  - Complex medical decision-making and outcomes in the ICU.

PMID- 22871786
TI  - Multiplexed single-molecule force proteolysis measurements using magnetic
      tweezers.
AB  - The generation and detection of mechanical forces is a ubiquitous aspect of cell
      physiology, with direct relevance to cancer metastasis(1), atherogenesis(2) and
      wound healing(3). In each of these examples, cells both exert force on their
      surroundings and simultaneously enzymatically remodel the extracellular matrix
      (ECM). The effect of forces on ECM has thus become an area of considerable
      interest due to its likely biological and medical importance(4-7). Single
      molecule techniques such as optical trapping(8), atomic force microscopy(9), and
      magnetic tweezers(10,11) allow researchers to probe the function of enzymes at a
      molecular level by exerting forces on individual proteins. Of these techniques,
      magnetic tweezers (MT) are notable for their low cost and high throughput. MT
      exert forces in the range of ~1-100 pN and can provide millisecond temporal
      resolution, qualities that are well matched to the study of enzyme mechanism at
      the single-molecule level(12). Here we report a highly parallelizable MT assay to
      study the effect of force on the proteolysis of single protein molecules. We
      present the specific example of the proteolysis of a trimeric collagen peptide by
      matrix metalloproteinase 1 (MMP-1); however, this assay can be easily adapted to
      study other substrates and proteases.

PMID- 22871787
TI  - The 6MWT: will different methods of instruction and measurement affect
      performance of healthy aging and older adults?
AB  - BACKGROUND AND PURPOSE: The Six-Minute Walk Test (6MWT) is commonly used to
      assess the fitness level of healthy adults and of older adults with disabilities.
      It can also be used as an intervention to increase walking endurance. However,
      its use may be limited in certain rehabilitation settings due to space
      requirements. If it can be shown that the measured linear distance walked in the
      6-minute walk is comparable to the distance walked as measured by a pedometer,
      the test may be more widely used in a variety of rehabilitation settings. In
      addition, questions exist as to whether the method of instruction ("walk as far
      as you can" vs "walk as fast as you can") can impact the rate of perceived
      exertion of the person performing the test. The purposes of this study were to
      assess for differences in the measured linear distance and from the gender-based
      predicted value when compared to the pedometer measurement. In addition, we
      assessed the difference, if any, in the rate of perceived exertion (RPE) using
      the 2 different methods of administration. Furthermore, the distance in meters
      walked using the 2 different methods of instruction was compared; likewise,
      comparisons were made of these values to predicted values. METHODS: A group of 26
      older adults participated in this descriptive study. After a practice trial, each
      person completed 2 linear trials using different methods of instruction, ("walk
      as fast as you can" or "walk as far as you can") of the 6MWT while wearing a DIGI
      WALKER SW-651 pedometer. Vital signs were taken before and after each trial.
      Linear distance, pedometer distance, and numeric value RPE were recorded.
      RESULTS: Paired t tests demonstrated no gender differences. An intraclass
      correlation coefficient (2,1) of 0.822 was calculated between all dependent
      variables. A repeated measures MANOVA was conducted to assess for differences
      between all variables resulting in no differences (F = 1.98; P = .13). Pairwise
      comparisons were also insignificant for the distance measurements except
      predicted value and pedometer fast P = .024. Paired t tests also demonstrated
      differences between RPE between trials (t = 2.15; P = .041). CONCLUSION: There
      was good agreement between these distance measures for the 6MWT. The use of a
      pedometer was found to be a valid measure of walking distance during the 6MWT. It
      was also found that the method of instruction made no differences in walking
      distance. Although the change was minimal on the Borg scale, the RPE was found to
      be significantly different between far and fast trials in healthy adults. From
      this study, it appears that that either mode of instruction is valid in healthy
      community-dwelling populations. Future studies should include populations with
      impairments.

PMID- 22871788
TI  - ExPAAC proceedings: Exercise training for individuals with heart failure.
AB  - Heart failure (HF) is considered a condition primarily associated with the older
      population, with approximately 80% of individuals admitted to the hospital with a
      diagnosis of HF being over the age of 65 years. With the 'aging of the
      population' in the United States the incidence of HF is expected to continue to
      rise. Therefore many of the older individuals seen by physical therapists for an
      array of conditions will have HF as a primary diagnosis or comorbidity which
      needs to be addressed in developing their plan of care. Current evidence supports
      the safety and efficacy of exercise training as a component in the overall
      medical management of individuals with stable HF regardless of age. The primary
      aims of this article are to review the benefits associated with exercise training
      in individuals with HF and present the current recommendations for aerobic,
      resistance and inspiratory muscle exercise training along with recommendations
      for monitoring and modifying exercise training programs. Clinically, exercise
      training has been shown to have a significant effect on improving functional
      capacity, oxygen consumption, 6-minute walk test distances, symptoms, self
      efficacy for exercise, and quality of life of individuals with HF. It is
      important that physical therapists adequately challenge individuals with HF with
      appropriate exercise intensities, while closely monitoring their patients, in
      order to achieve optimal functional benefits and quality of life.

PMID- 22871789
TI  - Adolescent beliefs about the acceptability of dating violence: does violent
      behavior change them?
AB  - This longitudinal study examined the interplay between teens' beliefs about the
      acceptability of dating violence and dating violence perpetration. The final
      sample included 82 teens aged 14 to 17 years. Families were recruited from
      truancy courts and juvenile probation and victim services offices. Teens
      participated in a baseline and a follow-up assessment spaced 3 months apart. At
      each assessment, teens reported on their beliefs about dating violence
      acceptability and their dating violence perpetration. Dating violence
      perpetration at baseline predicted beliefs accepting of violence at follow-up,
      after accounting for baseline levels of beliefs. Beliefs at baseline, however,
      did not predict dating violence perpetration at follow-up. Dating violence
      perpetration may lead to beliefs more accepting of such violence.

PMID- 22871790
TI  - "If something happened, I will leave it, let it go and move on": resiliency and
      victimized homeless women's attitudes toward mental health counseling.
AB  - In the present study, we draw on interviews conducted with 60 homeless women (N =
      60) in Detroit and Chicago about their experiences of violent criminal
      victimization and their attitudes toward accessing various postvictimization
      assistance-in particular, mental health counseling. Contrary to the research
      literature, which tends to overemphasize pathological responses to victimization
      within this population, what our data reveals is the extent to which victimized
      homeless women exhibit signs of resiliency through both attitudes and coping
      behaviors. Further, their expressed attitudes demonstrate the existence of a
      complex set of relationships between trauma, resiliency, and the desire to access
      mental health services. These findings we suggest have implications for the
      delivery of mental health services to this group.

PMID- 22871791
TI  - Long-term outcomes of young adults exposed to maltreatment: the role of
      educational experiences in promoting resilience to crime and violence in early
      adulthood.
AB  - This study investigates whether positive educational experiences in
      midadolescence mitigate the impact of exposure to substantiated maltreatment and
      reduces young adult antisocial behavior. While there is theoretical and empirical
      support for the mediating or moderating role of educational experiences on
      maltreatment and antisocial outcomes, few prospective studies exist. In this
      exploratory study, data are from the Rochester Youth Development Study (RYDS), a
      longitudinal panel study of 1,000 adolescents. The original sample included 73%
      males, and 85% African American or Hispanic youth of whom about 20% were
      maltreated. Measures in this study are from a combination of interview data and
      official records collected through age 23. Outcomes include self-reported crime
      and violence, arrest, and partner violence perpetration. Educational variables
      include midadolescent self-report of high school graduation, educational
      aspiration, college expectation, school commitment, teacher attachment, self
      reported grades, school GPA, attendance, and an additive index of all school
      assets. Multivariate path analysis controlled for gender, race/ethnicity,
      poverty, and early antisocial behavior. Path analysis examined whether
      educational experiences mediated the impact of maltreatment on antisocial
      outcomes. Although maltreatment was significantly predictive of criminal and
      violent behaviors, it only was weakly associated with educational experiences.
      The impact of maltreatment on arrest was weakly mediated (reduced) by educational
      GPA and by high school graduation. The additive index also mediated the impact of
      maltreatment on crime and violence. Maltreatment's impact on partner violence was
      also weakly mediated by school GPA. Interaction terms were used to test for
      moderation: only one significant effect was found: school GPA protects maltreated
      youth from perpetration of partner violence as young adults. Although there are
      few significant effects in a number of models, the research is consistent with a
      focus on promoting school achievement and completion among urban youth in
      general, in conjunction with addressing earlier antisocial behavior problems.

PMID- 22871792
TI  - [Prevalence of anti-CMV antibodies in blood donors in Ouagadougou (Burkina
      Faso)].
AB  - The aim of our study was to investigate the prevalence of CMV antibodies among
      blood donors at a regional blood transfusion center in Ouagadougou. Blood
      collected from 115 donors was tested for specific anti-CMV antibodies as well as
      routine markers. The donors ranged in age from 18 to 53 years (mean: 28.78 +/-
      8.9 years), and 72.2% were men. In all, 4.3% were positive for HIV, 12.2% for HBs
      Ag, 2.6% for HCV, and 1.7% for syphilis. Nearly all donors (n=106, 92.2%) had CMV
      IgG antibodies, but only 12.2% (n=14) IgM antibodies, and all of the latter were
      also positive for IgG. CMV infection was not related to the donors' HIV status
      (p=0.66). The seroprevalence of CMV infection was not statistically related to
      gender, age or occupational status. There was no significant difference in the
      prevalence of any routine markers between donors positive and negative for CMV.
      The high rate of CMV antibodies indicates that CMV infection is widespread in
      Burkina Faso. Although it is thus unnecessary to test blood donors routinely for
      CMV, immunodepressed and other risk subjects should receive CMV-negative or
      leukocyte-depleted blood.

PMID- 22871793
TI  - Depletion and reconstitution of macrophages in mice.
AB  - Macrophages are critical players in the innate immune response to infectious
      challenge or injury, initiating the innate immune response and directing the
      acquired immune response. Macrophage dysfunction can lead to an inability to
      mount an appropriate immune response and as such, has been implicated in many
      disease processes, including inflammatory bowel diseases. Macrophages display
      polarized phenotypes that are broadly divided into two categories. Classically
      activated macrophages, activated by stimulation with IFNgamma or LPS, play an
      essential role in response to bacterial challenge whereas alternatively activated
      macrophages, activated by IL-4 or IL-13, participate in debris scavenging and
      tissue remodeling and have been implicated in the resolution phase of
      inflammation. During an inflammatory response in vivo, macrophages are found amid
      a complex mixture of infiltrating immune cells and may participate by
      exacerbating or resolving inflammation. To define the role of macrophages in situ
      in a whole animal model, it is necessary to examine the effect of depleting
      macrophages from the complex environment. To ask questions about the role of
      macrophage phenotype in situ, phenotypically defined polarized macrophages can be
      derived ex vivo, from bone marrow aspirates and added back to mice, with or
      without prior depletion of macrophages. In the protocol presented here clodronate
      containing liposomes, versus PBS injected controls, were used to deplete colonic
      macrophages during dextran sodium sulfate (DSS)-induced colitis in mice. In
      addition, polarized macrophages were derived ex vivo and transferred to mice by
      intravenous injection. A caveat to this approach is that clodronate-containing
      liposomes deplete all professional phagocytes, including both dendritic cells and
      macrophages so to ensure the effect observed by depletion is macrophage-specific,
      reconstitution of phenotype by adoptive transfer of macrophages is necessary.
      Systemic macrophage depletion in mice can also be achieved by backcrossing mice
      onto a CD11b-DTR background, which is an excellent complementary approach. The
      advantage of clodronate-containing liposome-mediated depletion is that it does
      not require the time and expense involved in backcrossing mice and it can be used
      in mice regardless of the background of the mice (C57BL/6, BALB/c, or mixed
      background).

PMID- 22871794
TI  - T cell triggering: insights from 2D kinetics analysis of molecular interactions.
AB  - Interaction of the T cell receptor (TCR) with pathogen-derived peptide presented
      by the major histocompatibility complex (pMHC) molecule is central to adaptive
      immunity as it initiates intracellular signaling to trigger T cell response to
      infection. Kinetic parameters of this interaction have been under intensive
      investigation for more than two decades using soluble pMHCs and/or TCRs with at
      least one of them in the solution (three-dimensional (3D) methods). Recently,
      several techniques have been developed to enable kinetic analysis on live T cells
      with pMHCs presented by surrogate antigen presenting cells (APCs) or supported
      planar lipid bilayers (two-dimensional (2D) methods). Comparison of 2D versus 3D
      parameters reveals drastic differences with broader ranges of 2D affinities and
      on-rates and orders of magnitude faster 2D off-rates for functionally distinct
      pMHCs. Here we review new 2D data and discuss how it may impact previously
      developed models of T cell discrimination between pMHCs of different potencies.

PMID- 22871795
TI  - [Radiological diagnostics of spinal tumors. Part 2: special diagnostics of
      intradural tumors and tumor-like lesions].
AB  - Intradural tumors are classified into extramedullary and intramedullary
      localization. A distinct attribution to one of these compartments is essential
      for finding the appropriate diagnosis. In the radiological evaluation of
      intradural tumors magnetic resonance imaging (MRI) is the most important method
      and in contrast to osseous spinal tumors, radiography and computed tomography are
      of minor importance. According to the globally established WHO grading system,
      tumors of the central nervous system are histopathologically classified into four
      grades. Through grades I to IV malignancy and proliferative activity increase.
      Prognosis is inversely correlated to the WHO grade. Intradural tumors are
      generally treated by neurosurgeons. Besides neurological symptoms intradural
      tumors often cause spinal malpositioning. Thus knowledge of the most frequent
      intradural tumors and their characteristic magnetic resonance findings are
      important in the orthopedic practice.

PMID- 22871796
TI  - [Radiological diagnostics of spinal tumors. Part 1: general tumor diagnostics and
      special diagnostics of extradural tumors].
AB  - Radiological investigation of spinal tumors includes identification of the
      suspect lesions as well as their relation to surrounding critical structures,
      such as nerve roots and the myelon. With the use of computed tomography (CT) the
      delineation of bone and with magnetic resonance tomography the assessment of bone
      marrow and soft tissue are possible with high-spatial resolution and multi-planar
      reconstructions. The consolidation of clinical information, distribution pattern
      and morphology of the lesion itself results in the final radiological evaluation.
      Because of low invasiveness and complications, CT-guided biopsy is a common tool
      in cases of suspected lesions. With the help of multi-planar reconstructions even
      difficult approaches are possible without impairment of critical structures. This
      review article discusses typical imaging characteristics of common tumors
      originating from the vertebral column after a section on basic and general
      aspects of tumor diagnostics.

PMID- 22871797
TI  - Demonstration of a plasmonic thermocycler for the amplification of human androgen
      receptor DNA.
AB  - A plasmonic heating method for the polymerase chain reaction is demonstrated by
      the amplification of a section of the human androgen receptor gene. The
      thermocycler has a simple low-cost design, demonstrates excellent temperature
      stability and represents the first practical demonstration of plasmonic
      thermocycling.

PMID- 22871799
TI  - Open quantum dots: II. Probing the classical to quantum transition.
AB  - Open quantum dots provide a natural system in which to study both classical and
      quantum features of transport. From the classical point of view these  dots
      possess a mixed phase space which yields families of closed, regular orbits as
      well as an expansive sea of chaos. An important question concerns the manner in
      which these classical states evolve into the set of quantum states that populate
      the dot in the quantum limit. In the reverse direction, the manner in which the
      quantum states evolve to the classical world is governed strongly by Zurek's
      decoherence theory. This was discussed from the quantum perspective in an earlier
      review (Ferry et al 2011 Semicond. Sci. Technol.  26 043001). Here, we discuss
      the nature of the various classical states, how they are formed, how they
      progress to the quantum world, and the signatures that they create in
      magnetotransport and general conductance studies of these dots.

PMID- 22871800
TI  - Enhancement of 6-pentyl-alpha-pyrone fermentation activity in an extractive
      liquid-surface immobilization (Ext-LSI) system by mixing anion-exchange resin
      microparticles.
AB  - The addition of anion-exchange resin microparticles into a polyacrylonitrile
      (PAN) ballooned microsphere layer drastically enhanced the fermentative activity
      of Trichoderma atroviride AG2755-5NM398 in an extractive liquid-surface
      immobilization (Ext-LSI) system. The production of 6-pentyl-alpha-pyrone (6PP), a
      fungicidal secondary metabolite, was 1.92-fold higher than the control (PAN
      alone).

PMID- 22871798
TI  - Prognostic significance of TOP2A gene dosage in HER-2-negative breast cancer.
AB  - BACKGROUND: Previous studies showed the prognostic and predictive impact of human
      epidermal growth factor receptor 2 (HER-2) gene alterations analyzed separately
      and jointly with topoisomerase II alpha (TOP2A) gene alterations; however, the
      role of TOP2A gene abnormalities alone has not been thoroughly investigated.
      Additionally, TOP2A aberrations were typically studied in HER-2-positive (HER
      2(+)) tumors because these genes are frequently coamplified. Therefore, the
      knowledge concerning the impact of TOP2A abnormalities in HER-2-negative (HER-2(
      )) patients is scarce. This study aimed to investigate the clinical significance
      of TOP2A anomalies in breast cancer patients with HER-2(-) and HER-2(+) tumors.
      MATERIALS AND METHODS: Snap-frozen tumor samples from 322 consecutive stage I-III
      breast cancer patients were analyzed for TOP2A gene dosage using quantitative
      real-time PCR (qPCR). RESULTS: A high TOP2A gene dosage was found in 94 tumors
      (29%)-32% and 27% of HER-2(+) and HER-2(-) tumors, respectively. The mean TOP2A
      gene dosages in the HER-2(+) and HER-2(-) groups were 1.49 +/- 1.03 and 1.09 +/-
      0.35, respectively. High TOP2A gene dosage had an inverse prognostic impact in
      terms of shorter disease-free survival (DFS) and overall survival (OS) times in
      the entire group and in both the HER-2(-) and HER-2(+) subgroups. The unfavorable
      prognostic impact of TOP2A gene dosage was maintained in the multivariate Cox
      regression analysis in the entire group and in HER-2(-) patients. CONCLUSIONS: A
      high gene dosage of TOP2A determined using qPCR occurs frequently both in HER
      2(+) and HER-2(-) tumors and has a strong adverse prognostic impact.

PMID- 22871801
TI  - Long-term risk of vascular events after peripheral bypass surgery. A cohort
      study.
AB  - Patients with peripheral arterial disease (PAD) are at high risk of major
      ischaemic events. Long-term data of all major ischaemic events in PAD patients
      are scarce and outdated, especially for patients with severe PAD requiring bypass
      surgery. Our objective was to define their long-term prognosis and develop a
      prediction model which quantifies this risk up to a decade after surgery. We
      conducted a retrospective cohort study in patients from the Dutch Bypass Oral
      anticoagulants or Aspirin (BOA) Study; a multicentre randomised trial comparing
      oral anticoagulants with aspirin after infrainguinal bypass surgery. The primary
      outcome was the composite event of non-fatal myocardial infarction, non-fatal
      ischaemic stroke, major amputation, and vascular death. Cumulative risks were
      assessed by Kaplan-Meier analysis and independent determinants by multivariable
      Cox regression models. From 1995 until 2009, 482 patients were followed for a
      median period of 7.8 years. Follow-up was complete in 94%. Overall 60% of
      patients experienced a primary outcome event, of which the majority was a
      vascular death (30%), followed by major amputations (12%). The primary cause of
      vascular death was a cardiovascular event (29%), whereas the minority was due to
      complications directly related to PAD (6%). Within five years after bypass
      surgery vascular death occurred in about a quarter of patients and within 10
      years in nearly half of patients. This was double the rate as for non-vascular
      death. The primary outcome event occurred in over a third and over half of
      patients in 5 and 10 years after bypass surgery, respectively. From four
      independent determinants for the primary outcome event: age, diabetes, critical
      limb ischaemia, and prior vascular interventions, we developed a risk chart,
      which systematically classifies the 10-year risks of the primary outcome event,
      ranging from 25% to 85%. This study provided a detailed insight in the course of
      PAD long after peripheral bypass surgery and enables individual risk assessment
      of major fatal and non-fatal ischaemic events by means of cumulative incidences
      and a risk chart.

PMID- 22871802
TI  - (-)-(S)-Nakinadine B: first asymmetric synthesis.
AB  - (-)-(S)-Nakinadine B has been synthesized for the first time (in 9 steps and 17%
      overall yield from commercially available atropic acid) using the conjugate
      addition of lithium dibenzyl-amide to an N-alpha-phenylacryloyl SuperQuat
      derivative with in situ diastereoselective enolate protonation as the key step.

PMID- 22871803
TI  - Alkylaminopyridine-modified aluminum aminoterephthalate metal-organic frameworks
      as components of reactive self-detoxifying materials.
AB  - Aluminum aminoterephthalate MOF particulate materials (NH(2)-MIL-101(Al) and
      NH(2)-MIL-53(Al)), studied here as components of self-detoxifying surfaces,
      retained their reactivity following their covalent attachment to protective
      surfaces utilizing a newly developed strategy in which the MOF particles were
      deposited on a reactive adhesive composed of polyisobutylene/toluene diisocyanate
      (PIB/TDI) blends. Following MOF attachment and curing, the MOF primary amino
      groups were functionalized with highly nucleophilic 4-methylaminopyridine (4-MAP)
      by disuccinimidyl suberate-activated conjugation. The resulting MOF-4-MAP
      modified PIB/TDI elastomeric films were mechanically flexible and capable of
      degrading diisopropyl fluorophosphate (DFP), a chemical threat simulant.

PMID- 22871804
TI  - Imaging high-dimensional spatial entanglement with a camera.
AB  - The light produced by parametric down-conversion shows strong spatial
      entanglement that leads to violations of EPR criteria for separability.
      Historically, such studies have been performed by scanning a single-element,
      single-photon detector across a detection plane. Here we show that modern
      electron-multiplying charge-coupled device cameras can measure correlations in
      both position and momentum across a multi-pixel field of view. This capability
      allows us to observe entanglement of around 2,500 spatial states and demonstrate
      Einstein-Podolsky-Rosen type correlations by more than two orders of magnitude.
      More generally, our work shows that cameras can lead to important new
      capabilities in quantum optics and quantum information science.

PMID- 22871805
TI  - FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory.
AB  - During the primary immune response, CD8 memory emerges from an environment of
      strong immune activation. The FoxP3(+) regulatory CD4 T-cell subset (Treg) is
      known as a key suppressive component of the immune system. Here we report that
      Tregs are required for the generation of functional CD8 memory. In the absence of
      Tregs during priming, the resulting memory cells proliferate poorly and fail to
      differentiate into functional cytotoxic secondary effectors following antigen
      reactivation. We find that the Tregs act early, during the expansion phase of
      primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory
      precursors. This crucial new role of Tregs has implications for optimal vaccine
      development.

PMID- 22871806
TI  - Multimode circuit optomechanics near the quantum limit.
AB  - The coupling of distinct systems underlies nearly all physical phenomena. A basic
      instance is that of interacting harmonic oscillators, giving rise to, for
      example, the phonon eigenmodes in a lattice. Of particular importance are the
      interactions in hybrid quantum systems, which can combine the benefits of each
      part in quantum technologies. Here we investigate a hybrid optomechanical system
      having three degrees of freedom, consisting of a microwave cavity and two
      micromechanical beams with closely spaced frequencies around 32 MHz and no direct
      interaction. We record the first evidence of tripartite optomechanical mixing,
      implying that the eigenmodes are combinations of one photonic and two phononic
      modes. We identify an asymmetric dark mode having a long lifetime.
      Simultaneously, we operate the nearly macroscopic mechanical modes close to the
      motional quantum ground state, down to 1.8 thermal quanta, achieved by back
      action cooling. These results constitute an important advance towards engineering
      of entangled motional states.

PMID- 22871807
TI  - Skyrmion flow near room temperature in an ultralow current density.
AB  - The manipulation of spin textures with electric currents is an important
      challenge in the field of spintronics. Many attempts have been made to
      electrically drive magnetic domain walls in ferromagnets, yet the necessary
      current density remains quite high (~10(7) A cm(-2)). A recent neutron study
      combining Hall effect measurements has shown that an ultralow current density of
      J~10(2) A cm(-2) can trigger the rotational and translational motion of the
      skyrmion lattice in MnSi, a helimagnet, within a narrow temperature range.
      Raising the temperature range in which skyrmions are stable and reducing the
      current required to drive them are therefore desirable objectives. Here we
      demonstrate near-room-temperature motion of skyrmions driven by electrical
      currents in a microdevice composed of the helimagnet FeGe, by using in-situ
      Lorentz transmission electron microscopy. The rotational and translational
      motions of skyrmion crystal begin under critical current densities far below 100
      A cm(-2).

PMID- 22871808
TI  - Light-induced spiral mass transport in azo-polymer films under vortex-beam
      illumination.
AB  - When an azobenzene-containing polymer film is exposed to non-uniform
      illumination, a light-induced mass migration process may be induced, leading to
      the formation of relief patterns on the polymer-free surface. Despite many years
      of research effort, several aspects of this phenomenon remain poorly understood.
      Here we report the appearance of spiral-shaped relief patterns on the polymer
      film under the illumination of focused Laguerre-Gauss beams with helical
      wavefronts and an optical vortex at their axis. The induced spiral reliefs are
      sensitive to the vortex topological charge and to the wavefront handedness. These
      findings are unexpected because the doughnut-shaped intensity profile of Laguerre
      Gauss beams contains no information about the wavefront handedness. We propose a
      model that explains the main features of this phenomenon through the surface
      mediated interference of the longitudinal and transverse components of the
      optical field. These results may find applications in optical nanolithography and
      optical-field nanoimaging.

PMID- 22871809
TI  - Controlled delivery of bioactive molecules into live cells using the bacterial
      mechanosensitive channel MscL.
AB  - Bacterial mechanosensitive channels are some of the largest pores in nature. In
      particular, MscL, with a pore diameter >25 A, allows passage of large organic
      ions and small proteins. Functional MscL reconstitution into lipids has been
      proposed for applications in vesicular-based drug release. Here we show that
      these channels can be functionally expressed in mammalian cells to afford rapid
      controlled uptake of membrane-impermeable molecules. We first demonstrate that
      MscL gating in response to increased membrane tension is preserved in mammalian
      cell membranes. Molecular delivery is controlled by adopting an established
      method of MscL charge-induced activation. We then determine pore size limitations
      using fluorescently labelled model cargoes. Finally, we activate MscL to
      introduce the cell-impermeable bi-cyclic peptide phalloidin, a specific marker
      for actin filaments, into cells. We propose that MscL will be a useful tool for
      gated and controlled delivery of bioactive molecules into cells.

PMID- 22871810
TI  - Dynamic histone marks in the hippocampus and cortex facilitate memory
      consolidation.
AB  - Memory consolidation requires a timely controlled interplay between the
      hippocampus, a brain region important for memory formation, and the cortex, a
      region recruited for memory storage. Here we show that memory consolidation is
      associated with specific epigenetic modifications on histone proteins that have a
      distinct dynamic in these brain areas. While in the hippocampus, histone post
      translational modifications (PTMs) are rapidly and transiently activated after
      learning, in the cortex they are induced with delay but persist over time. When
      these histone PTMs are increased in vivo by transgenic intervention or intense
      training, they facilitate memory consolidation. Conversely, when they are
      pharmacologically blocked, memory consolidation is impaired. These histone PTMs
      are further associated with the expression of the immediate early gene zif268, a
      transcription factor that favours memory consolidation. These findings reveal the
      spatiotemporal dynamics of histone marks during memory consolidation, and
      demonstrate their inherent 'mnemonic' property.

PMID- 22871811
TI  - Higgs transition from a magnetic Coulomb liquid to a ferromagnet in Yb2Ti2O7.
AB  - In a class of frustrated magnets known as spin ice, magnetic monopoles emerge as
      classical defects and interact via the magnetic Coulomb law. With quantum
      mechanical interactions, these magnetic charges are carried by fractionalized
      bosonic quasi-particles, spinons, which can undergo Bose-Einstein condensation
      through a first-order transition via the Higgs mechanism. Here, we report
      evidence of a Higgs transition from a magnetic Coulomb liquid to a ferromagnet in
      single-crystal Yb(2)Ti(2)O(7). Polarized neutron scattering experiments show that
      the diffuse [111]-rod scattering and pinch-point features, which develop on
      cooling are suddenly suppressed below T(C)~0.21 K, where magnetic Bragg peaks and
      a full depolarization of the neutron spins are observed with thermal hysteresis,
      indicating a first-order ferromagnetic transition. Our results are explained on
      the basis of a quantum spin-ice model, whose high-temperature phase is
      effectively described as a magnetic Coulomb liquid, whereas the ground state
      shows a nearly collinear ferromagnetism with gapped spin excitations.

PMID- 22871812
TI  - High-resolution three-dimensional partially coherent diffraction imaging.
AB  - The wave properties of light, particularly its coherence, are responsible for
      interference effects, which can be exploited in powerful imaging applications.
      Coherent diffractive imaging relies heavily on coherence and has recently
      experienced rapid growth. Coherent diffractive imaging recovers an object from
      its diffraction pattern by computational phasing with the potential of wavelength
      limited resolution. Diminished coherence results in reconstructions that suffer
      from artefacts or fail completely. Here we demonstrate ab initio phasing of
      partially coherent diffraction patterns in three dimensions, while simultaneously
      determining the coherence properties of the illuminating wavefield. Both the
      dramatic improvements in image interpretability and the three-dimensional
      evaluation of the coherence will have broad implications for quantitative imaging
      of nanostructures and wavefield characterization with X-rays and electrons.

PMID- 22871813
TI  - Post-transcriptional spliceosomes are retained in nuclear speckles until splicing
      completion.
AB  - There is little quantitative information regarding how much splicing occurs co
      transcriptionally in higher eukaryotes, and it remains unclear where precisely
      splicing occurs in the nucleus. Here we determine the global extent of co- and
      post-transcriptional splicing in mammalian cells, and their respective subnuclear
      locations, using antibodies that specifically recognize phosphorylated SF3b155 (P
      SF3b155) found only in catalytically activated/active spliceosomes.
      Quantification of chromatin- and nucleoplasm-associated P-SF3b155 after
      fractionation of HeLa cell nuclei, reveals that ~80% of pre-mRNA splicing occurs
      co-transcriptionally. Active spliceosomes localize in situ to regions of
      decompacted chromatin, at the periphery of or within nuclear speckles.
      Immunofluorescence microscopy with anti-P-SF3b155 antibodies, coupled with
      transcription inhibition and a block in splicing after SF3b155 phosphorylation,
      indicates that post-transcriptional splicing occurs in nuclear speckles and that
      release of post-transcriptionally spliced mRNA from speckles is coupled to the
      nuclear mRNA export pathway. Our data provide new insights into when and where
      splicing occurs in cells.

PMID- 22871815
TI  - Observation of resistively detected hole spin resonance and zero-field pseudo
      spin splitting in epitaxial graphene.
AB  - Electronic carriers in graphene show a high carrier mobility at room temperature.
      Thus, this system is widely viewed as a potential future charge-based high-speed
      electronic material to complement-or replace-silicon. At the same time, the spin
      properties of graphene have suggested improved capability for spin-based
      electronics or spintronics and spin-based quantum computing. As a result, the
      detection, characterization and transport of spin have become topics of interest
      in graphene. Here we report a microwave photo-excited transport study of
      monolayer and trilayer graphene that reveals an unexpectedly strong microwave
      induced electrical response and dual microwave-induced resonances in the dc
      resistance. The results suggest the resistive detection of spin resonance, and
      provide a measurement of the g-factor, the spin relaxation time and the sub
      lattice degeneracy splitting at zero magnetic field.

PMID- 22871814
TI  - Distinct loops in arrestin differentially regulate ligand binding within the GPCR
      opsin.
AB  - G-protein-coupled receptors are universally regulated by arrestin binding. Here
      we show that rod arrestin induces uptake of the agonist all-trans-retinal
      [corrected] in only half the population of phosphorylated opsin in the native
      membrane. Agonist uptake blocks subsequent entry of the inverse agonist 11-cis
      retinal (that is, regeneration of rhodopsin), but regeneration is not blocked in
      the other half of aporeceptors. Environmentally sensitive fluorophores attached
      to arrestin reported that conformational changes in loop(V-VI) (N-domain) are
      coupled to the entry of agonist, while loop(XVIII-XIX) (C-domain) engages the
      aporeceptor even before agonist is added. The data are most consistent with a
      model in which each domain of arrestin engages its own aporeceptor, and the
      different binding preferences of the domains lead to asymmetric ligand binding by
      the aporeceptors. Such a mechanism would protect the rod cell in bright light by
      concurrently sequestering toxic all-trans-retinal [corrected] and allowing
      regeneration with 11-cis-retinal.

PMID- 22871816
TI  - Red blood cell subpopulations in freshly drawn blood: application of proteomics
      and metabolomics to a decades-long biological issue.
AB  - BACKGROUND: It has long been known that red blood cells comprise various
      subpopulations, which can be separated through Percoll density gradients.
      MATERIALS AND METHODS: In this study, we performed integrated flow cytometry,
      proteomic and metabolomic analyses on five distinct red blood cell subpopulations
      obtained by Percoll density gradient separation of freshly drawn leucocyte
      depleted erythrocyte concentrates. The relation of density gradient fractions to
      cell age was confirmed through band 4.1a/4.1b assays. RESULTS: We observed a
      decrease in size and increase in cell rugosity in older (denser) populations.
      Metabolomic analysis of fraction 5 (the oldest population) showed a decrease of
      glycolytic metabolism and of anti-oxidant defence-related mechanisms, resulting
      in decreased activation of the pentose phosphate pathway, less accumulation of
      NADPH and reduced glutathione and increased levels of oxidized glutathione. These
      observations strengthen conclusions about the role of oxidative stress in
      erythrocyte ageing in vivo, in analogy with results of recent in vitro studies.
      On the other hand, no substantial proteomic differences were observed among
      fractions. This result was partly explained by intrinsic technical limitations of
      the two-dimensional gel electrophoresis approach and the probable clearance from
      the bloodstream of erythrocytes with membrane protein alterations. Since this
      clearance effect is not present in vitro (in blood bank conditions), proteomic
      studies have shown substantial membrane lesions in ageing red blood cells in
      vitro. CONCLUSION: This analysis shows that the three main red blood cell
      subpopulations, accounting for over 92% of the total RBC, are rather homogeneous
      soon after withdrawal. Major age-related alterations in vivo probably affect
      enzyme activities through post-translational mechanisms rather than through
      changes in the overall proteomic profile of RBC.

PMID- 22871817
TI  - Effects of anaemia on haemodynamic and clinical parameters in apparently stable
      preterm infants.
AB  - BACKGROUND: The criteria for erythrocyte transfusion in stable premature infants
      are currently controversial. Haemodynamic measurements are not common in
      transfusion practice. The purpose of this study was to determine whether
      haemodynamic measurements could be helpful as objective criterion for transfusion
      decisions. We, therefore, evaluated clinical and haemodynamic changes in stable,
      anaemic, premature infants before and after transfusion using our current blood
      transfusion protocol based on a haematocrit threshold (<24%) and the
      neonatologist's discretion. MATERIAL AND METHODS: Stable premature infants with a
      haematocrit level <=30% were prospectively enrolled into the study. Cerebral,
      intestinal and renal blood flow velocities, cardiac function parameters and vital
      signs were measured up to three times following every routine haematocrit
      analysis. Moreover, transfused infants were evaluated three more times: directly
      before transfusion, and 24 hours and 72 hours after transfusion. RESULTS: Thirty
      six infants were enrolled and 23 of them were transfused. Subgroup analysis of
      transfused infants showed a significant decrease in cerebral blood flow
      velocities, cardiac output and heart rate. These changes persisted after
      transfusion. In the entire cohort, the degree of anaemia correlated with the
      increase of cerebral blood flow velocities, heart rate and cardiac output.
      DISCUSSION: Cerebral blood velocities in the anterior cerebral artery might
      represent an objective Doppler sonographic criterion indicating the need for
      transfusion. The measurement of these velocities is non-invasive and quick and
      easy to perform. However, a randomised, controlled trial is necessary before a
      formal recommendation can be made.

PMID- 22871818
TI  - A simple diagnostic strategy for RhD typing in discrepant cases in the Indian
      population.
AB  - BACKGROUND: The D antigen is the most immunogenic antigen in the Rh system. D
      variants must be considered if there is a significant discrepancy in the strength
      of reaction obtained with different anti-D reagents, a discrepancy between
      current and historical test results and if anti-D is detected in an individual
      serologically typed as RhD positive. A panel of monoclonal anti-D reagents can be
      used to identify partial D and weak D variants. The aim of this study was to
      develop a strategy for RhD typing in discrepant cases. MATERIALS AND METHODS:
      Sixty RhD discrepant samples referred to our Institute for confirmation of RhD
      status were tested with a panel of 12 monoclonal anti-D reagents (ALBAclone
      advanced partial RhD typing kit) and Rh phenotype was determined using C, c, D,
      E, and e antisera. RESULTS: Ninety-three percent of the RhD discrepant cases were
      classified into weak and partial D using this kit. Among the D variants
      characterised, 37% belonged to DFR, 23% to DOL, 12% to weak D, and the remaining
      21% to DAR, DV, DMH, DCS and DVI categories. Ninety-seven percent of the D
      variants were "C" antigen positive. Out of the panel of 12 monoclonal anti-D
      used, cell line LHM-70/45 gave negative reactions with all RhD discrepant cases
      and cell lines LHM-76/59, LHM-76/55 and ESD-1 gave positive reactions with all 60
      RhD discrepant cases studied. DISCUSSION: The Advanced partial D kit was very
      useful in characterising and identifying D variants in the Indian population. A
      preliminary strategy for the detection and identification of D variants in
      discrepant cases could be to test for the presence of "C" antigen with anti-C,
      and for "D" antigen with anti-D of cell line LHM 70/45. A more comprehensive, but
      simple way to identify D variants in routine RhD typing is to use two anti-D
      reagents i.e LHM 70/45 and one out of LHM-76/59, LHM-76/55 and ESD-1. D variants
      can be further characterised by using the partial D typing kit and molecular
      genotyping in specialised laboratories.

PMID- 22871819
TI  - The challenge and paradox in serology RhD typing for blood donors and patients.

PMID- 22871820
TI  - Do manual and automated processes with distinct additive solutions affect whole
      blood-derived platelet components differently?

PMID- 22871821
TI  - Geographical variations in current clinical practice on transfusions and iron
      chelation therapy across various transfusion-dependent anaemias.
AB  - BACKGROUND AND OBJECTIVES: Many patients with chronic anaemia require blood
      transfusions as part of their treatment regimen. As a result, iron overload will
      inevitably develop if not adequately managed by iron chelation therapy. There are
      many guidelines relating to transfusion and chelation practices for patients with
      transfusion-dependent anaemia; however, there is a lack of information on how
      treatment practices differ around the world. The objective of this manuscript is
      to highlight key features of current transfusion and chelation management,
      including similarities and differences across various anaemias and between
      geographical regions worldwide. MATERIALS AND METHODS: Data collected at study
      entry to the multicentre Evaluation of Patients' Iron Chelation with Exjade
      (EPIC) study, which recruited 1,744 patients with a variety of transfusion
      dependent anaemias across 23 countries from three geographic regions, were
      assessed. These analyses compared transfusion and chelation treatment prior to
      the start of study treatment, together with iron burden assessed at study entry
      by serum ferritin, liver iron concentration and labile plasma iron levels.
      RESULTS AND CONCLUSIONS: Data show that transfusion and iron chelation practices
      differ between anaemias and between geographical regions; this may be linked to
      availability and accessibility of transfusion and chelation therapy, patients'
      compliance, physicians' attitudes, costs and use of treatment guidelines.
      Approximately 60% of these transfusion-dependent patients were severely iron
      overloaded with a serum ferritin level over 2,500 ng/mL, indicating that the
      risks of iron burden may have been underestimated and current iron chelation
      therapy, if considered, may not have been adequate to control iron burden.

PMID- 22871822
TI  - We have a specific duty to maximise the safety of related donors.

PMID- 22871823
TI  - Screening of related donors and peripheral blood stem cell collection practices
      at different Italian apheresis centres.
AB  - BACKGROUND: Recommendations on eligibility criteria for donation of
      haematopoietic stem cells, management of collection of the cells and follow-up
      mainly concern unrelated donors. The aim of this study was to analyse the
      screening of related donors and collection practices at different Italian
      apheresis centres. MATERIALS AND METHODS: A questionnaire regarding eligibility
      criteria for related haematopoietic stem cell donors, their peripheral blood
      collections and early follow-up was sent to several apheresis units. Data from
      the full charts of 500 candidates, screened between May 2005 and December 2009,
      were retrospectively evaluated. RESULTS: The donors' records, eligibility
      criteria, collections and follow-up are managed differently in each centre. Of
      the 500 evaluable candidates (51.2% male, 49.8% female; median age 47 years,
      range 13-77), 26.4% underwent thorough screening according to Italian Bone Marrow
      Donor Registry standards, while local protocols were applied to 73.6%; 91
      candidates (18.2%) proved ineligible for donation. In the end, 352 donors (53.4%
      male, 46.6% female; median age 45 years, range 16-76) underwent 508
      leukaphereses. Central venous catheters were used in 8.0% of donors, mainly in
      one centre. Unsuitable pre-apheresis peripheral blood parameters were reported in
      38.7% of the aphereses. Leukapheresis-related adverse events were recorded in
      23.0% of the procedures, with a drop-out rate of 0.2% for severe events. No
      donation-related fatalities occurred. The CD34+ cell yield was <2*10(6)/kg of
      recipient's body weight from 1.1% of donors >=70 years old. DISCUSSION: More
      uniformity in donor screening procedures, management of peripheral blood
      collection and follow-up should be planned at a national level to maximise the
      safety of related donors.

PMID- 22871824
TI  - Estimating the effectiveness of acellular pertussis vaccines.

PMID- 22871826
TI  - Unexpectedly limited durability of immunity following acellular pertussis
      vaccination in preadolescents in a North American outbreak.

PMID- 22871827
TI  - Specific biological diagnoses are needed to determine the durability of pertussis
      vaccine-induced immunity.

PMID- 22871828
TI  - Prevalence of peripheral abnormalities on ultra-widefield greenlight (532 nm)
      autofluorescence imaging at a tertiary care center.
AB  - PURPOSE: To assess the prevalence of peripheral fundus autofluorescence (FAF)
      abnormalities in a variety of diseases seen at a tertiary retina clinic. METHODS:
      We conducted a retrospective review of cases seen at the Doheny Eye Institute
      between November 2009 and May 2011, who had ultra-widefield FAF and pseudocolor
      imaging performed on new models of scanning laser ophthalmoscopes. Patients with
      a history of previous therapies that could alter the FAF findings, including
      vitrectomy, cryotherapy, laser photocoagulation, or photodynamic therapy, were
      excluded from the analysis. Based on their primary diagnosis the eyes were
      grouped into nine disease categories: age-related macular degeneration, central
      serous retinopathy, dystrophy, inflammatory disorders, ocular tumor, retinal
      vascular disorders, other, normal, and unknown. All FAF and accompanying
      pseudocolor images were reviewed independently by two reading center-certified
      graders. RESULTS: A total of 470 eyes of 248 patients were included for analysis
      of which 461 eyes had images of sufficient quality for grading. The prevalence of
      peripheral findings was 65.5% (n = 302) for FAF images and 68.5% (n = 316) for
      the pseudocolor images (P < 0.001). The prevalence of peripheral abnormalities
      differed significantly between the disease categories ranging from 18.5% to 82.2%
      for FAF and 18.5% to 82.4% for pseudocolor images. CONCLUSIONS: Peripheral FAF
      abnormalities are frequent and readily revealed by FAF imaging. Interestingly,
      even cases with presumably macular disease demonstrated a high prevalence of
      peripheral findings. Further investigation in prospective studies is warranted.

PMID- 22871829
TI  - Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo
      and in vitro studies.
AB  - PURPOSE: Lutein protects retinal neurons by its anti-oxidative and anti-apoptotic
      properties in ischemia/reperfusion (I/R) injury while its anti-inflammatory
      effects remain unknown. As Muller cells play a critical role in retinal
      inflammation, the effect of lutein on Muller cells was investigated in a murine
      model of I/R injury and a culture model of hypoxic damage. METHODS: Unilateral
      retinal I/R was induced by a blockade of internal carotid artery using the
      intraluminal method in mice. Ischemia was maintained for 2 hours followed by 22
      hours of reperfusion, during which either lutein (0.2 mg/kg) or vehicle was
      administered. Flash electroretinogram (flash ERG) and glial fibrillary acidic
      protein (GFAP) activation were assessed. Lutein's effect on Muller cells was
      further evaluated in immortalized rat Muller cells (rMC-1) challenged with cobalt
      chloride-induced hypoxia. Levels of IL-1beta, cyclooxygenase-2 (Cox-2), TNFalpha,
      and nuclear factor-NF-kappa-B (NF-kappaB) were examined by Western blot analysis.
      RESULTS: Lutein treatment minimized deterioration of b-wave/a-wave ratio and
      oscillatory potentials as well as inhibited up-regulation of GFAP in retinal I/R
      injury. In cultured Muller cells, lutein treatment increased cell viability and
      reduced level of nuclear NF-kappaB, IL-1beta, and Cox-2, but not TNFalpha after
      hypoxic injury. CONCLUSIONS: Reduced gliosis in I/R retina was observed with
      lutein treatment, which may contribute to preserved retinal function. Less
      production of pro-inflammatory factors from Muller cells suggested an anti
      inflammatory role of lutein in retinal ischemic/hypoxic injury. Together with our
      previous studies, our results suggest that lutein protected the retina from
      ischemic/hypoxic damage by its anti-oxidative, anti-apoptotic, and anti
      inflammatory properties.

PMID- 22871830
TI  - Associations between local retinal thickness and function in early diabetes.
AB  - PURPOSE: To investigate, using multifocal electroretinography (mfERG) and optical
      coherence tomography (OCT), potential spatial associations between local
      neuroretinal function and local retinal thickness in patients with diabetes.
      METHODS: Forty-five patients without retinopathy (10 with Type 1 diabetes; 35
      with Type 2 diabetes; 49.9 +/- 10.9 years old) and 29 age-similar controls (47.0
      +/- 12.8 years old) were studied. N1-P1 amplitude (AMP) and P1 implicit time (IT)
      of mfERGs within the central approximately 20 degrees  diameter were compared to
      spatially corresponding full retinal thickness measurements acquired by Stratus
      OCT3. AMP and IT were converted to Z-scores and retinal thickness was converted
      to percentile values. Local abnormalities were defined as P <= 0.023. Subject
      group differences were examined using t-tests. Retinal thickness was compared to
      mfERGs to determine spatial associations. RESULTS: Average retinal thicknesses
      were similar for all subject groups. The Type 1 group and controls had similar IT
      and AMP. The Type 2 group had reduced AMP and longer IT than the controls and the
      Type 1 group (P < 0.001). Local associations between retinal thickness and mfERGs
      were not significant within any subject group or individuals, even for abnormal
      locations (P >= 0.09). Abnormalities in most measures were greater in the patient
      groups than in the controls (P < 0.008) except retinal thinning in the Type 1
      group. CONCLUSIONS: Local neuroretinal function is not associated with full
      retinal thickness measured locally in patients with diabetes and no retinopathy,
      even in abnormal locations. Full retinal thickness measured locally by OCT is not
      a surrogate for mfERGs in early diabetes. Neuroretinal function in Type 2
      diabetes is worse than in Type 1 diabetes and controls. Fewer subjects in the
      Type 1 group could be a potential limitation.

PMID- 22871831
TI  - Activated blood coagulation factor X (FXa) induces angiogenic growth factor
      expression in human retinal pigment epithelial cells.
AB  - PURPOSE: To determine the transcriptional regulation of the blood coagulation
      factor X (FX) in cultured human retinal pigment epithelial (RPE) cells, and
      whether the effects of FXa on the chemotaxis and expression of angiogenic growth
      factors are mediated by autocrine growth factor signaling. METHODS: Alterations
      in gene expression and secretion of growth factors were determined by real-time
      RT-PCR and ELISA, respectively. Cellular proliferation and chemotaxis were
      investigated with a bromodeoxyuridine immunoassay and a Boyden chamber assay,
      respectively. RESULTS: The gene expression of FX in RPE cells was increased by
      hypoxia and prostaglandin E(2), and decreased by blood serum, FXa, thrombin,
      transforming growth factor beta (TGF-beta1), and platelet-derived growth factor
      (PDGF). The serum-induced downregulation of FX was mediated by thrombin and TGF
      beta signaling. FXa induced chemotaxis of RPE cells via activation of the p38
      mitogen-activated protein kinase signal transduction pathway. FXa also induced
      expression of vascular endothelial growth factor (VEGF), heparin-binding
      epidermal growth factor-like growth factor (HB-EGF), and basic fibroblast growth
      factor (bFGF), as well as release of VEGF, bFGF, and TGF-beta1 from RPE cells.
      The stimulatory effects of FXa on the expression of growth factors and secretion
      of VEGF were prevented by inhibition of the TGF-beta activin receptor-like
      kinase, but not by the thrombin inhibitor hirudin. FXa induced phosphorylation of
      ERK1/2, p38, and Akt proteins. CONCLUSIONS: FXa induces chemotaxis of RPE cells,
      as well as expression and release of angiogenic growth factors from RPE cells,
      including VEGF. The effects of FXa on the expression and secretion of VEGF are
      mediated by autocrine/paracrine TGF-beta signaling.

PMID- 22871832
TI  - Antifibrotic effects of quercetin in primary orbital fibroblasts and orbital fat
      tissue cultures of Graves' orbitopathy.
AB  - PURPOSE: We investigated the effects of quercetin on fibrotic markers and matrix
      metalloproteinases (MMPs) in primary cells and whole orbital tissues from Graves'
      orbitopathy (GO). METHODS: Orbital fat tissues were harvested from GO for primary
      cell and tissue cultures during orbital fat decompression. To determine
      noncytotoxic dose and time of quercetin treatment, 3-(4,5-dimethyl-thiazol-2-yl)
      2,5-diphenyl-tetrazolium bromide (MTT) assay and LDH release assay were
      performed. The effects of quercetin on fibrosis were evaluated according to a
      scratch wound closure assay, and Western blotting for expression of fibronectin,
      collagen Ialpha, alpha-smooth muscle actin with or without TGF-beta stimulation,
      and MMP-2, -7, -9, and tissue inhibitor of metalloproteinase-1 with or without IL
      1beta stimulation. The gelatinolytic activities of MMP-2 and MMP-9 were measured
      using gelatin zymography. In tissue cultures, MMP secretion and MMP and collagen
      Ialpha mRNA levels were determined by enzyme-linked immunosorbent assays and
      reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS:
      Quercetin significantly inhibited cell migration at nontoxic concentrations. In
      primary cells, quercetin dose-dependently downregulated expression of TGF-beta
      stimulated fibronectin and collagen Ialpha, and IL-1beta-enhanced MMP-2 and MMP
      9. However, without IL-1beta stimulation, 10-50 MUM of quercetin increased MMP-2
      expression and activity, but dose-dependently suppressed MMP-9 expression and
      activity. In tissue cultures, quercetin dose-dependently inhibited MMP-2 and -9
      activity and secretion, but 30 and 50 MUM of quercetin increased tissue MMP-2
      mRNA. MMP-9 and collagen Ialpha mRNA levels were dose-dependently suppressed.
      CONCLUSIONS: Quercetin inhibited fibrotic markers and affected MMP-2 and MMP-9
      activities in primary cell and orbital fat tissue cultures from GO at nontoxic
      concentrations. Our results support the potential use of quercetin for active
      inflammation and treatment or prevention of chronic fibrosis in GO.

PMID- 22871833
TI  - Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy,
      and correlation with VEGF and inflammatory cytokines.
AB  - PURPOSE: We determined vitreous levels of prostaglandin E2 (PGE(2)), VEGF, and 15
      other cytokines in diabetic and nondiabetic patients undergoing vitrectomy.
      METHODS: Of 26 eyes of 26 patients enrolled consecutively, 13 eyes underwent
      vitrectomy for complications related to proliferative diabetic retinopathy, and
      the other 13 for epiretinal membrane, macular hole, vitreous opacities, or
      dislocated intraocular lens. Undiluted vitreous samples were taken at the time of
      surgery and frozen immediately at -80 degrees C, and later analyzed for PGE(2),
      VEGF, and 15 other cytokines. RESULTS: PGE(2) levels were 53% higher in diabetic
      eyes. Mean +/- standard deviation PGE(2) levels were 25.11 +/- 11 pg/mL and 16.40
      +/- 7 pg/mL in diabetic and nondiabetic eyes, respectively (P < 0.03). Mean +/-
      standard deviation VEGF levels were 2225 +/- 3798 pg/mL and 66 +/- 185 pg/mL in
      diabetic and nondiabetic eyes, respectively (P < 0.001). Other cytokines,
      including eotaxin-1, growth related oncogene (GRO), interleukin (IL)-6, IL-8,
      interferon-gamma-inducible protein of 10 kDa (IP-10), monocyte chemoattractant
      protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and platelet-derived
      growth factor-AA, also were elevated significantly in diabetic eyes. A
      significant correlation was seen between PGE(2) levels and IP-10 and VEGF (P =
      0.04). CONCLUSIONS: PGE(2) levels are significantly higher in the vitreous of
      patients with complications from proliferative diabetic retinopathy, and
      correlate with IP-10 and VEGF. The results of our study suggest that PGE(2) may
      have a pathogenic role in diabetic retinopathy and implicates a potential
      therapeutic role for nonsteroidal anti-inflammatory drugs. (ClinicalTrials.gov
      number, NCT01609881.).

PMID- 22871834
TI  - Effects of erythropoietin-dextran microparticle-based PLGA/PLA microspheres on
      RGCs.
AB  - PURPOSE: We explored the neuroprotective effects of erythropoietin (EPO)-loaded
      dextran microparticle-based Poly(DL-lactide-co-glycolide)/Poly(DL-lactide)
      (PLGA/PLA) microspheres (EPO-dextran PLGA/PLA microspheres) on retinal ganglion
      cells (RGCs) in optic nerve crush rats for a prolonged period of time. METHODS:
      EPO-dextran PLGA/PLA microspheres were prepared first by a novel solid-in-oil-in
      water (S/O/W) technique. Then, the in vitro EPO release profile was assessed.
      Afterward, the bioactive effect of EPO released from EPO-dextran PLGA/PLA
      microspheres was explored in vitro on the retinal explants. Lastly, the
      neuroprotective effects of EPO-dextran PLGA/PLA microspheres on RGCs were
      evaluated in optic nerve crush rats with TUNEL staining for apoptotic RGCs. The
      level of glial fibrillary acidic protein (GFAP) expressed in retina was explored
      by immunohistochemistry staining. Survival RGCs were observed by DiI retrograde
      labeling using a DiI fluorescent tracer (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate). RESULTS: The results demonstrated that
      a sustained release of EPO from PLGA/PLA microspheres could last for at least 60
      days. EPO released from the microspheres showed as efficaciously
      neuroregenerative as EPO protein solution on retinal explants (P = 0.2554 for
      neurite density, P = 0.1004 for neurite length). TUNEL staining revealed that EPO
      dextran PLGA/PLA microspheres remarkably reduced RGCs death when compared to the
      control (untreated) group (P < 0.01 at five days and one week post-crush, P <
      0.05 at two weeks post-crush). Increased GFAP expression in retina was reduced
      greatly in EPO-dextran PLGA/PLA microspheres-administrated rats two weeks post
      optic nerve crush. DiI retrograde labeling revealed that a single injection of
      EPO-dextran PLGA/PLA microspheres significantly promoted RGCs survival (P < 0.01
      at four and eight weeks post-crush). CONCLUSIONS: A single intravitreal injection
      of EPO-dextran PLGA/PLA microspheres appeared to have a prolonged protective
      effect on RGCs in optic nerve crush rats. The PLGA/PLA microspheres may be a
      feasible protein delivery system, such as EPO, to intravitreal injection for
      retinal degeneration diseases.

PMID- 22871835
TI  - Retinal nerve fiber layer thickness reproducibility using seven different OCT
      instruments.
AB  - PURPOSE: The clinical utility of new optical coherence tomography (OCT)
      instruments strongly depends on measurements reproducibility. The aim of this
      study was to assess retinal nerve fiber layer (RNFL) thickness reproducibility
      using six different spectral-domain OCTs (SD-OCTs) and one time-domain OCT.
      METHODS: RNFL thickness (average and four quadrant) from six SD-OCTs (Spectral
      OCT/SLO OPKO/OTI, 3D-OCT 2000 Topcon, RS-3000 NIDEK, Cirrus HD-OCT Zeiss, RTVue
      100 Optovue, and Spectralis Heidelberg) and one time-domain OCT (Stratus OCT
      Zeiss) was measured twice in 38 right eyes of 38 randomly chosen healthy
      volunteers by two masked operators. Inter- and intraoperator reproducibility was
      evaluated by the intraclass correlation coefficient (ICC), coefficient of
      variation (CV), and Bland-Altman test analysis. Instrument-to-instrument
      reproducibility was determined by ANOVA for repeated measures. We also tested how
      the devices disagree in terms of systemic bias and random error using a
      structural equation model. RESULTS: Mean RNFL average thickness ranged from 90.08
      MUm to 106.51 MUm. Cirrus and Heidelberg showed the thinnest RNFL values in all
      measurements, Topcon the highest. ICC, CV, and Bland-Altman plots showed variable
      inter- and intraoperator agreement depending on the instrument. Heidelberg
      demonstrated the best interoperator (ICC, 0.92; CV, 1.56%) and intraoperator
      (ICC, 0.94 and 0.95; CV, 1.28% and 1.26%, respectively, for operator A and
      operator B) agreement for average RNFL thickness. CONCLUSIONS: Heidelberg
      demonstrated the higher agreement in inter- and intraoperator reproducibility,
      Optovue the worst. In light of our error analysis results, we found that a scale
      bias among instruments could interfere with a thorough RNFL monitoring,
      suggesting that best monitoring is obtained with the same operator and the same
      device.

PMID- 22871836
TI  - Genome-wide expression profiling of patients with primary open angle glaucoma.
AB  - PURPOSE: To identify differentially expressed genes and to elucidate gene
      interaction networks and molecular pathways possibly contributing to the
      development of POAG. METHODS: Genome-wide expression profiling experiments were
      carried out using ABI high-density oligonucleotide microarrays in leukocytes from
      25 POAG patients and 12 age-, ethnicity-, and sex-matched normal controls.
      Significantly modulated genes were defined as those with a false discovery rate
      (FDR) <0.01 and an absolute fold change (FC) >1.5. These genes are then mapped to
      relevant biologic processes and pathways. RESULTS: We identified 563 genes that
      were significantly dysregulated (410 upregulated and 153 downregulated) in POAG
      compared with normal controls ("POAG gene signature"). These genes were
      significantly enriched with functions related to, among others, nucleoside,
      nucleotide, and nucleic acid metabolism, the mitogen-activated protein kinase
      kinase kinase cascade, apoptosis, protein synthesis, cell cycle, intracellular
      signaling cascade, and nervous system development and function. Among the most
      significantly altered canonical pathways in POAG were the ephrin receptor
      signaling, ubiquitin proteasome pathway, hypoxia signaling, neuregulin, and G
      protein coupled receptor signaling. Network analysis revealed potentially
      critical roles of UBE2, TBP, GNAQ, SUMO1, CREB, p70S6k, IFNG, and CaMKII that are
      interacting with NF-kappaB, ubiquitin, proteasome, PI3K/AKT, IL12, and PDGF in
      the disease pathogenesis. CONCLUSIONS: Our study revealed blood gene signatures
      that clearly distinguish POAG patients and normal controls, as well as altered
      pathways that may shed light on POAG pathogenesis.

PMID- 22871837
TI  - Moving from PROMs to POEMs for glaucoma care: a qualitative scoping exercise.
AB  - PURPOSE: Patient-reported outcome measures (PROMs) are accepted widely as
      important outcomes in comparative effectiveness research. Over 30 PROMs have been
      described for use in glaucoma research, but their role in routine care is
      undefined. Our study explores the views of patients with glaucoma and their
      carers on the feasibility and content of a glaucoma PROM for use in day-to-day
      clinical practice. METHODS: Focus groups were held with 71 participants
      facilitated by 23 staff working in the field of ophthalmology. Comparisons were
      made among themes derived from this exercise using simple thematic analysis and
      currently available health-related quality of life (HRQoL) instruments. RESULTS:
      Participants were supportive of reporting their outcomes if the instrument was
      short, practical, and useful. Potential barriers to the use of PROMs, including
      bureaucratic overload and accessibility issues, were identified. Measuring health
      outcome and patient experience was important to participants. No freely available
      instrument covers all the domains identified, particularly knowledge and
      understanding. A novel instrument, a glaucoma patient-reported outcome and
      experience measure (POEM) is proposed. This addresses three aspects of outcome
      (fear of blindness, acceptability of treatment/side effects, and impact on daily
      life), and three aspects of experience (safety, respect, and understanding).
      CONCLUSIONS: Using PROMs routinely in the management of glaucoma presents
      significant challenges. Although current instruments (questionnaires) cover many
      of the participants' key domains, no single instrument covered them all. Further
      research is required to determine the feasibility (resources required), and
      validity and reliability of the proposed glaucoma POEM in clinical care.

PMID- 22871838
TI  - Detection of prosecretory mitogen lacritin in nonprimate tears primarily as a C
      terminal-like fragment.
AB  - PURPOSE: Lacritin is a human tear glycoprotein that promotes basal tear protein
      secretion in cultured rat lacrimal acinar cells and proliferation of subconfluent
      human corneal epithelial cells. When topically added to rabbit eyes, lacritin
      promotes basal tearing. Despite these activities on several species, lacritin's
      presence in nonprimate tears or other tissues has not been explored. Here we
      probed for lacritin in normal horse tears. METHODS: Sequences were collected from
      the Ensembl genomic alignment of human LACRT gene with high-quality draft horse
      genome (EquCab2.0) and analyzed. Normal horse tears were collected and assayed by
      Western blotting, ELISA, and mass spectrometry. Newly generated rabbit
      antibodies, respectively, against N- and C-terminal regions of human lacritin
      were employed. RESULTS: Identity was 75% and 45%, respectively, at nucleotide and
      protein levels. Structural features were conserved, including a C-terminal
      amphipathic alpha-helix. Anti-C-terminal antibodies strongly detected a ~13 kDa
      band in horse tears that was validated by mass spectrometry. In human tears, the
      same antibody detected uncleaved lacritin (~24 kDa) strongly and C-terminal
      fragments of ~13 and ~11 kDa weakly. Anti-N-terminal antibodies were slightly
      reactive with a ~24 kDa horse antigen and showed no reaction with the anti-C
      terminal-reactive ~13 kDa species. Similar respective levels of horse C-terminal
      versus N-terminal immunoreactivity were apparent by ELISA. CONCLUSIONS: Lacritin
      is present in horse tears, largely as a C-terminal fragment homologous to the
      mitogenic and bactericidal region in human lacritin, suggesting potential benefit
      in corneal wound repair.

PMID- 22871839
TI  - Neural and vascular responses to fused binocular stimuli: a VEP and fNIRS study.
AB  - PURPOSE: The aim of our study was to investigate the correlation between neural
      and hemodynamic responses to stereoscopic stimuli recorded over visual cortex.
      METHODS: Test stimuli consisted of a static checkerboard (checks) and dichoptic
      static random dot (RD) presentations with no binocular disparity (ZD) or with
      horizontal disparity (HD). Hemodynamic responses were recorded from right and
      left occipital sites using functional near-infrared spectroscopy (fNIRS). Visual
      evoked potentials (VEPs) were recorded over three occipital sites to the onset of
      the same stimuli. RESULTS: Early components, N1 and P2, were sensitive to HD,
      suggesting that an enhanced N1-reduced P2 complex could be an indicator of
      binocular disparity and stereopsis. VEPs to checks and ZD stimulation were
      similar. fNIRS recordings showed changes in hemodynamic activation from baseline
      levels in response to all stimuli. In general, HD elicited a larger vascular
      response than ZD. Oxyhemoglobin concentration (HbO) was correlated with the VEP
      amplitude during the checks and HD presentations. CONCLUSIONS: We report an
      association between neural and hemodynamic activation in response to checks and
      HD. In addition, the results suggested that N1-P2 complex in the VEP could be a
      neural marker for stereopsis and fNIRS demonstrated differences in HbO.
      Specifically, checks and HD elicited larger hemodynamic responses than random dot
      patterns without binocular disparity.

PMID- 22871840
TI  - Monitoring of cornea elastic properties changes during UV-A/riboflavin-induced
      corneal collagen cross-linking using supersonic shear wave imaging: a pilot
      study.
AB  - PURPOSE: Keratoconus disease or post-LASIK corneal ectasia are increasingly
      treated using UV-A/riboflavin-induced corneal collagen cross-linking (CXL).
      However, this treatment suffers from a lack of techniques to provide an
      assessment in real-time of the CXL effects. Here, we investigated the potential
      interest of corneal elasticity as a biomarker of the efficacy of this treatment.
      METHODS: For this purpose, supersonic shear wave imaging (SSI) was performed both
      ex vivo and in vivo on porcine eyes before and after CXL. Based on ultrasonic
      scanners providing ultrafast frame rates (~30 kHz), the SSI technique generates
      and tracks the propagation of shear waves in tissues. It provides two- and three
      dimensional (2-D and 3-D) quantitative maps of the corneal elasticity. RESULTS:
      After CXL, quantitative maps of corneal stiffness clearly depicted the cross
      linked area with a typical 200-MUm lateral resolution. The CXL resulted in a 56%
      +/- 15% increase of the shear wave speed for corneas treated in vivo (n = 4).
      CONCLUSIONS: The in vivo CXL experiments performed on pigs demonstrated that the
      quantitative estimation of local stiffness and the 2-D elastic maps of the
      corneal surface provide an efficient way to monitor the local efficacy of corneal
      cross-linking.

PMID- 22871841
TI  - Using flow cytometry to compare the dynamics of photoreceptor outer segment
      phagocytosis in iPS-derived RPE cells.
AB  - PURPOSE: Retinal pigment epithelium (RPE) autologous grafts can be readily
      derived from induced pluripotent stem (iPS) cells. It is critical to stringently
      characterize iPS-RPE using standardized and quantifiable methods to be confident
      that they are safe and adequate replacements for diseased RPE before utilizing
      them in clinical settings. One important and required function is that the iPS
      RPE phagocytose photoreceptor outer segments (POS). METHODS: We developed a flow
      cytometry-based assay to monitor binding and internalization of FITC labeled POS
      by ARPE-19, human fetal RPE (hfRPE), and two types of iPS-RPE. Expression and
      density of alpha(v)beta5 integrin, CD36, and MerTK receptors, which are required
      for phagocytosis, were compared. RESULTS: Trypsinization of treated RPE cells
      results in the release of bound POS. The number of freed POS, the percentage of
      cells that internalized POS, the brightness of the FITC signal from the cells,
      and the surface density of the phagocytosis receptors on single RPE cells were
      measured using flow cytometry. These assays reveal that receptor density is
      dynamic during differentiation and this can affect the binding and
      internalization dynamics of the RPE cells. Highly differentiated iPS-RPE
      phagocytose POS more efficiently than hfRPE. CONCLUSIONS: Caution should be
      exercised to not use RPE grafts until demonstrating that they are fully
      functional. The density of the phagocytosis receptors is dynamic and may be used
      as a predictor for how well the iPS-RPE cells will function in vivo. The
      phagocytosis dynamics observed between iPS-RPE and primary RPE is very
      encouraging and adds to mounting evidence that iPS-RPE may be a viable
      replacement for dysfunctional or dying RPE in human patients.

PMID- 22871842
TI  - Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using
      near infrared light.
AB  - PURPOSE: We evaluated the efficacy and safety of photochemical corneal stiffening
      by palladium bacteriochlorin 13'-(2-sulfoethyl)amide dipotassium salt (WST11) and
      near infrared (NIR) illumination, using ex vivo and in vivo rabbit eye models.
      METHODS: Corneas of post mortem rabbits and living rabbits were pretreated
      topically with 2.5 mg/mL WST11 in saline or in 20% dextran T-500 (WST-D), washed
      and illuminated with an NIR diode laser (755 nm, 10 mW/cm(2). Studies with
      corneas of untreated fellow eyes served as controls. Tensile strength
      measurements, histopathology, electron spin resonance, and optical spectroscopy
      and fluorescence microscopy were used to assess treatment effects. Comparative
      studies were performed with standard riboflavin/ultraviolet-A light (UVA)
      treatment. RESULTS: WST11/NIR treatment significantly increased corneal stiffness
      following ex vivo or in vivo treatment, compared to untreated contralateral eyes.
      The incremental ultimate stress and Young's modulus of treated corneas increased
      by 45, 113, 115%, and 10, 79, and 174% following 10, 20, and 30 minutes of
      incubation with WST11, respectively. WST-D/NIR had a similar stiffening effect,
      but markedly reduced post-treatment edema and shorter time of epithelial healing.
      WST11/NIR and WST-D/NIR generate hydroxyl and superoxide radicals, but no singlet
      oxygen in the cornea. Histology demonstrated a reduction in the keratocyte
      population in the anterior half of the corneal stroma, without damage to the
      endothelium. CONCLUSIONS: Treatment of rabbit corneas, with either WST11/NIR or
      WST-D/NIR, increases their biomechanical strength through a mechanism that does
      not involve singlet oxygen. The WST-D/NIR treatment showed less adverse effects,
      demonstrating a new potential for clinical use in keratoconus and corneal ectasia
      after refractive surgery.

PMID- 22871843
TI  - Whole animal perfusion fixation for rodents.
AB  - The goal of fixation is to rapidly and uniformly preserve tissue in a life-like
      state. While placing tissue directly in fixative works well for small pieces of
      tissue, larger specimens like the intact brain pose a problem for immersion
      fixation because the fixative does not reach all regions of the tissue at the
      same rate (5,7). Often, changes in response to hypoxia begin before the tissue
      can be preserved (12). The advantage of directly perfusing fixative through the
      circulatory system is that the chemical can quickly reach every corner of the
      organism using the natural vascular network. In order to utilize the circulatory
      system most effectively, care must be taken to match physiological pressures (3).
      It is important to note that physiological pressures are dependent on the species
      used. Techniques for perfusion fixation vary depending on the tissue to be fixed
      and how the tissue will be processed following fixation. In this video, we
      describe a low-cost, rapid, controlled and uniform fixation procedure using 4%
      paraformaldehyde perfused via the vascular system: through the heart of the rat
      to obtain the best possible preservation of the brain for immunohistochemistry.
      The main advantage of this technique (vs. gravity-fed systems) is that the
      circulatory system is utilized most effectively.

PMID- 22871846
TI  - The cover. New ways on Banquereau.

PMID- 22871849
TI  - Groups propose plan to accredit controversial stem cell therapy clinics.

PMID- 22871850
TI  - Oncology drugs enter the US market faster than in Europe but cost more.

PMID- 22871851
TI  - Endocrine Society seeks better testing to determine endocrine disruptor health
      risks.

PMID- 22871852
TI  - Database of food-borne pathogen genomes created.

PMID- 22871857
TI  - Helicopter vs ground transportation for patients with trauma.

PMID- 22871858
TI  - Helicopter vs ground transportation for patients with trauma.

PMID- 22871859
TI  - Helicopter vs ground transportation for patients with trauma.

PMID- 22871860
TI  - Helicopter vs ground transportation for patients with trauma.

PMID- 22871862
TI  - Abciximab vs thrombectomy for reperfusion in myocardial infarction.

PMID- 22871864
TI  - Brachytherapy vs whole-breast irradiation for breast cancer.

PMID- 22871866
TI  - Transcatheter valve replacement for aortic stenosis: balancing benefits, risks,
      and expectations.

PMID- 22871867
TI  - The importance of potential studies that have not existed and registration of
      observational data sets.

PMID- 22871868
TI  - Payment reform for primary care within the accountable care organization: a
      critical issue for health system reform.

PMID- 22871869
TI  - A piece of my mind. VIP and UIP.

PMID- 22871871
TI  - Trends in serum lipids among US youths aged 6 to 19 years, 1988-2010.
AB  - CONTEXT: For more than 20 years, primary prevention of coronary heart disease has
      included strategies intended to improve overall serum lipid concentrations among
      youths. OBJECTIVE: To examine trends in lipid concentrations among youths from
      1988-1994 through 2007-2010. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      analysis of serum lipid concentrations among 16,116 youths aged 6 to 19 years who
      participated in the nationally representative National Health and Nutrition
      Examination Survey during 3 time periods: 1988-1994, 1999-2002, and 2007-2010.
      MAIN OUTCOME MEASURES: Among all youths, mean serum total cholesterol (TC), non
      high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein
      cholesterol (HDL-C); and among adolescents only, low-density lipoprotein
      cholesterol (LDL-C) and geometric mean triglyceride levels. Trends in adverse
      lipid concentrations are reported for TC levels of 200 mg/dL and greater, non-HDL
      C levels of 145 mg/dL and greater, HDL-C levels of less than 40 mg/dL, LDL-C
      levels of 130 mg/dL and greater, and triglyceride levels of 130 mg/dL and
      greater. RESULTS: Among youths aged 6 to 19 years between 1988-1994 and 2007
      2010, there was a decrease in mean TC (from 165 mg/dL [95% CI, 164-167] to 160
      mg/dL [95% CI, 158-161]; P < .001) and a decrease in the prevalence of elevated
      TC (from 11.3% [95% CI, 9.8%-12.7%] to 8.1% [95% CI, 6.7%-9.5%]; P = .002). Mean
      HDL-C significantly increased between 1988-1994 and 2007-2010, but the prevalence
      of low HDL-C did not change. Mean non-HDL-C and prevalence of elevated non-HDL-C
      both significantly decreased over the study period. In 2007-2010, 22% (95% CI,
      20.3%-23.6%) of youths had either a low HDL-C level or high non-HDL-C, which was
      lower than the 27.2% (95% CI, 24.6%-29.7%) in 1988-1994 (P = .001). Among
      adolescents (aged 12-19 years) between 1988-1994 and 2007-2010, there was a
      decrease in mean LDL-C (from 95 mg/dL [95% CI, 92-98] to 90 mg/dL [95% CI, 88
      91]; P = .003) and a decrease in geometric mean triglycerides (from 82 mg/dL [95%
      CI, 78-86] to 73 mg/dL [95% CI, 70-76]; P < .001). Prevalence of elevated LDL-C
      and triglycerides between 1988-1994 and 2007-2010 also significantly decreased.
      CONCLUSIONS: Between 1988-1994 and 2007-2010, a favorable trend in serum lipid
      concentrations was observed among youths in the United States but almost 1 in 10
      had elevated TC in 2007-2010.

PMID- 22871870
TI  - Association of weight status with mortality in adults with incident diabetes.
AB  - CONTEXT: Type 2 diabetes in normal-weight adults (body mass index [BMI] <25) is a
      representation of the metabolically obese normal-weight phenotype with unknown
      mortality consequences. OBJECTIVE: To test the association of weight status with
      mortality in adults with new-onset diabetes in order to minimize the influence of
      diabetes duration and voluntary weight loss on mortality. DESIGN, SETTING, AND
      PARTICIPANTS: Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis
      Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008;
      Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring
      Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011. A total
      of 2625 participants with incident diabetes contributed 27,125 person-years of
      follow-up. Included were men and women (age >40 years) who developed incident
      diabetes based on fasting glucose 126 mg/dL or greater or newly initiated
      diabetes medication and who had concurrent measurements of BMI. Participants were
      classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if
      BMI was 25 or greater. MAIN OUTCOME MEASURES: Total, cardiovascular, and
      noncardiovascular mortality. RESULTS: The proportion of adults who were normal
      weight at the time of incident diabetes ranged from 9% to 21% (overall 12%).
      During follow-up, 449 participants died: 178 from cardiovascular causes and 253
      from noncardiovascular causes (18 were not classified). The rates of total,
      cardiovascular, and noncardiovascular mortality were higher in normal-weight
      participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively) than
      in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years,
      respectively). After adjustment for demographic characteristics and blood
      pressure, lipid levels, waist circumference, and smoking status, hazard ratios
      comparing normal-weight participants with overweight/obese participants for
      total, cardiovascular, and noncardiovascular mortality were 2.08 (95% CI, 1.52
      2.85), 1.52 (95% CI, 0.89-2.58), and 2.32 (95% CI, 1.55-3.48), respectively.
      CONCLUSION: Adults who were normal weight at the time of incident diabetes had
      higher mortality than adults who are overweight or obese.

PMID- 22871872
TI  - Silvery-gray hair in a newborn.

PMID- 22871873
TI  - Beyond the obesity paradox in diabetes: fitness, fatness, and mortality.

PMID- 22871874
TI  - Declining cholesterol levels in US youths: a reason for optimism.

PMID- 22871877
TI  - JAMA patient page. Dry eye.

PMID- 22871878
TI  - Volumetric considerations for lower eyelid and midface rejuvenation.
AB  - PURPOSE OF REVIEW: With the accepted understanding of volume loss as one of the
      main factors in facial aging, oculofacial surgeons are embracing the concept of
      'removing' less and 'filling' more. The purpose of this review is to present an
      update of the different alternatives and techniques for lower eyelid and midface
      restoration/rejuvenation using filler agents. RECENT FINDINGS: When a filler
      agent is chosen, the aim is to provide some lift, support and sculpting to the
      treated area. Nonpermanent or semi-permanent fillers are most widely accepted by
      physicians mainly because there is a lower possibility of complications. The
      involutional changes in the facial structures are a continuous process; this
      requires reassessment and variation in techniques in addition to choosing
      different products at different ages. Safety, support capability, ease of
      injection and cost are the factors to consider when choosing an injectable
      implant. But, physicochemical structure or rheological properties, such as
      viscosity and elasticity, enable the clinician to objectively select the most
      appropriate injectable implant depending on the specific anatomical area. An
      injectable with low viscosity may be ideal for lip enhancement wherein softness
      is required, whereas a higher viscosity filler or a harder filler may be better
      indicated for structure and support in the midface. SUMMARY: Given the wide
      variety of filler materials available, clinicians and surgeons must be able to
      select products based on safety, lifting or sculpting capability and rheological
      properties, such as viscosity and elasticity. These factors provide an objective
      parameter of how the filler agent will perform in a specific area.

PMID- 22871879
TI  - Adjustable sutures:  an update.
AB  - PURPOSE OF REVIEW: This review discusses outcomes and recent advances in the use
      of adjustable sutures in strabismus surgery for children and adults. RECENT
      FINDINGS: Several large studies have compared the success rates of strabismus
      surgery with adjustable sutures versus nonadjustable sutures by the same surgeon
      or group of surgeons, and demonstrate a significant increase in the short-term
      alignment for both children and adults with the use of adjustable sutures.
      Modifications of adjustable sutures technique that make adjustable sutures a more
      attractive option, especially for children. SUMMARY: Recent studies have shown
      better short-term success rates when using adjustable sutures versus conventional
      sutures in strabismus surgery. Improved outcomes combined with increased options
      in surgical technique may lead more surgeons to use adjustable sutures in both
      children and adults.

PMID- 22871880
TI  - A new approach to the classification of neonatal corneal opacities.
AB  - PURPOSE OF REVIEW: Neonatal corneal opacification (NCO) describes the loss of
      corneal transparency at or soon after (<4 weeks) birth. Historically, the
      literature is strewn with terminology that has been at best misleading and at
      worst, a hindrance to selecting the appropriate treatment plan for, accurate
      genotype-phenotype correlation of and a better understanding of the entities that
      present in the clinic. RECENT FINDINGS: Recent literature has demonstrated that
      certain terms such as 'sclerocornea' are unhelpful when alluding to total NCO.
      The term Peters anomaly has also become a 'waste paper basket' diagnosis for
      anterior segment developmental anomalies. A new classification of NCO is
      suggested by the author, which allows a better understanding of the cause of NCO
      and the likely prognosis of therapeutic intervention. SUMMARY: This
      classification system should help the clinician understand the cause of NCO,
      better explain this to parents and recognize those conditions in which
      therapeutic intervention may be helpful. By understanding which conditions have a
      better chance of interventional success and by employing outcome definitions that
      take into consideration the developing neurobiological system of the infant brain
      and the effects of vision on its development, it is hoped more children with NCO
      will attain useful visual function.

PMID- 22871881
TI  - Type I neurofibromatosis:  a geno-oculo-dermatologic update.
AB  - PURPOSE OF REVIEW: This review will focus on the recent clinical insights into
      type I neurofibromatosis (NF1), the most common geno-oculo-dermatosis. Advances
      in the treatment will also be reviewed. RECENT FINDINGS: NF1 shares phenotypic
      features with disorders such as Legius syndrome, type 2 neurofibromatosis (NF2),
      and multiple lentigenes syndrome. Molecular diagnostic testing aids in diagnosing
      young children with still-evolving clinical signs and distinguishes NF1 from
      these other conditions. The management of optic pathway gliomas (OPGs) remains
      controversial. OPGs may enlarge in later childhood and beyond such that longer
      ocular surveillance may be appropriate. Retinal nerve fiber layer thickness
      inversely correlates with OPGs and decreased vision. There is suspected
      correlation of cerebral arteriopathy risk with the presence of OPGs. Ciliary body
      cysts and retinal pigmentary abnormalities may also be markers of NF1. Studies
      continue to confirm the utility of Lisch nodules as a diagnostic marker in older
      children and adults and seem to correlate with underlying iris pigmentation and
      sunlight exposure. Promising therapies are being developed based on NF1's central
      role in the RAS/RHEB/mTOR signal transduction pathway. SUMMARY: Continuing
      advances are enhancing the diagnosis and management of NF1. Current clinical
      trials use agents that target the RAS/mTOR signal transduction pathway and alter
      microenvironmental factors that contribute to tumor progression.

PMID- 22871882
TI  - DNA display of PNA-tagged ligands: a versatile strategy to screen libraries and
      control geometry of multidentate ligands.
AB  - Over the past decade, several technologies have emerged to access nucleic acid
      tagged libraries and select the fittest compound within such libraries. This
      perspective focuses on recent development with PNA-tagged small molecules
      displayed on DNA templates for screening purposes and to probe the optimal
      geometry in multivalent interactions.

PMID- 22871883
TI  - Sarcopenia is associated with postoperative infection and delayed recovery from
      colorectal cancer resection surgery.
AB  - BACKGROUND: Skeletal muscle depletion (sarcopenia) predicts morbidity and
      mortality in the elderly and cancer patients. METHODS: We tested whether
      sarcopenia predicts primary colorectal cancer resection outcomes in stage II-IV
      patients (n=234). Sarcopenia was assessed using preoperative computed tomography
      images. Administrative hospitalisation data encompassing the index surgical
      admission, direct transfers for inpatient rehabilitation care and hospital re
      admissions within 30 days was searched for International Classification of
      Disease (ICD)-10 codes for postoperative infections and inpatient rehabilitation
      care and used to calculate length of stay (LOS). RESULTS: Overall, 38.9% were
      sarcopenic; 16.7% had an infection and 9.0% had inpatient rehabilitation care.
      Length of stay was longer for sarcopenic patients overall (15.9 +/- 14.2 days vs
      12.3 +/- 9.8 days, P=0.038) and especially in those >= 65 years (20.2 +/- 16.9
      days vs 13.1 +/- 8.3 days, P=0.008). Infection risk was greater for sarcopenic
      patients overall (23.7% vs 12.5%; P=0.025), and especially those >= 65 years
      (29.6% vs 8.8%, P=0.005). Most (90%) inpatient rehabilitation care was in
      patients >= 65 years. Inpatient rehabilitation was more common in sarcopenic
      patients overall (14.3% vs 5.6%; P=0.024) and those >= 65 years (24.1% vs 10.7%,
      P=0.06). In a multivariate model in patients >= 65 years, sarcopenia was an
      independent predictor of both infection (odds ratio (OR) 4.6, (95% confidence
      interval (CI) 1.5, 13.9) P<0.01) and rehabilitation care (OR 3.1 (95% CI 1.04,
      9.4) P<0.04). CONCLUSION: Sarcopenia predicts postoperative infections, inpatient
      rehabilitation care and consequently a longer LOS.

PMID- 22871884
TI  - Investigating factors associated with adherence behaviour in patients with
      chronic myeloid leukemia: an observational patient-centered outcome study.
AB  - BACKGROUND: Optimal adherence to imatinib therapy is of paramount importance to
      maximise treatment effectiveness in patients with chronic myeloid leukaemia
      (CML). The main objective of this study was to investigate patient-reported
      personal factors associated with adherence behaviour. METHODS: Analysis was
      conducted on 413 CML patients receiving long-term therapy with imatinib.
      Adherence behaviour was measured with the Morisky Medication Adherence Scale and
      personal factors investigated included: quality of life, perceived social
      support, fatigue, symptom burden, psychological wellbeing and desire for
      additional information. Key socio-demographic and treatment-related factors were
      also taken into account. Univariate and multivariate logistic regression analyses
      were used to investigate factors associated with optimal adherence to therapy.
      RESULTS: In all, 53% of patients reported an optimal adherence behaviour. The
      final multivariate model retained the following variables as independent
      predictors of optimal adherence to therapy: desire for more information (ref.
      no), odds ratio (OR)=0.43 (95% confidence interval (CI), 0.29-0.66; P<0.001),
      social support (higher score representing greater support), OR=1.29 (95% CI, 1.11
      1.49; P<0.001) and concomitant drug burden (ref. no), OR=1.82 (95% CI, 1.18-2.80;
      P=0.006). CONCLUSION: This study suggests that a higher level of social support,
      satisfaction with information received and concomitant drug burden are the main
      factors associated with greater adherence to long-term imatinib therapy.

PMID- 22871885
TI  - Nomogram prediction for overall survival of patients diagnosed with cervical
      cancer.
AB  - BACKGROUND: Nomograms are predictive tools that are widely used for estimating
      cancer prognosis. The aim of this study was to develop a nomogram for the
      prediction of overall survival (OS) in patients diagnosed with cervical cancer.
      METHODS: Cervical cancer databases of two large institutions were analysed.
      Overall survival was defined as the clinical endpoint and OS probabilities were
      estimated using the Kaplan-Meier method. Based on the results of survival
      analyses and previous studies, relevant covariates were identified, a nomogram
      was constructed and validated using bootstrap cross-validation. Discrimination of
      the nomogram was quantified with the concordance probability. RESULTS: In total,
      528 consecutive patients with invasive cervical cancer, who had all nomogram
      variables available, were identified. Mean 5-year OS rates for patients with
      International Federation of Gynecologists and Obstetricians (FIGO) stage IA, IB,
      II, III, and IV were 99.0%, 88.6%, 65.8%, 58.7%, and 41.5%, respectively. Seventy
      six cancer-related deaths were observed during the follow-up period. FIGO stage,
      tumour size, age, histologic subtype, lymph node ratio, and parametrial
      involvement were selected as nomogram covariates. The prognostic performance of
      the model exceeded that of FIGO stage alone and the model's estimated optimism
      corrected concordance probability was 0.723, indicating accurate prediction of
      OS. We present the prediction model as nomogram and provide a web-based risk
      calculator (http://www.ccc.ac.at/gcu). CONCLUSION: Based on six easily available
      parameters, a novel statistical model to predict OS of patients diagnosed with
      cervical cancer was constructed and validated. The model was implemented in a
      nomogram and provides accurate prediction of individual patients' prognosis
      useful for patient counselling and deciding on follow-up strategies.

PMID- 22871886
TI  - Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to
      risk category and treatment response.
AB  - BACKGROUND: High plasma osteopontin (OPN) has been linked to tumour hypoxia,
      metastasis, and poor prognosis. This study aims to assess whether plasma
      osteopontin was a biomarker of increasing progression within prostate cancer
      (PCa) prognostic groups and whether it reflected treatment response to local and
      systemic therapies. METHODS: Baseline OPN was determined in men with localised
      (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC
      MET; n=37). Receiver-operating curves (ROC) were generated to describe the
      accuracy of OPN for distinguishing between localised risk groups or localised vs
      metastatic disease. We also measured OPN pre- and posttreatment, following
      radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation
      (AD) or taxane-based chemotherapy. RESULTS: The CRPC-MET patients had increased
      baseline values (mean 219; 56-513 ng ml(-1); P<0.0001) compared with the
      localised, non-metastatic group (mean 72; 12-438 ng ml(-1)). The area under the
      ROC to differentiate localised vs metastatic disease was improved when OPN was
      added to prostate-specific antigen (PSA) (0.943-0.969). Osteopontin neither
      distinguished high-risk PCa from other localised PCa nor correlated with serum
      PSA at baseline. Osteopontin levels reduced in low-risk patients after radical
      prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027),
      but not after EBRT or AD. CONCLUSION: Plasma OPN is as good as PSA at predicting
      treatment response in CRPC-MET patients after chemotherapy. Our data do not
      support the use of plasma OPN as a biomarker of increasing tumour burden within
      localised PCa.

PMID- 22871887
TI  - Relationship between carotid artery mechanics and the spontaneous baroreflex:  a
      noninvasive investigation in normal humans.
AB  - OBJECTIVES: This study addressed the relationship between spontaneous baroreflex
      sensitivity and carotid mechanical properties in a clinical setting. METHODS: In
      191 normal volunteers (age range 20-60 years, mean 44 +/- 13), spontaneous
      indices of baroreflex regulation were obtained noninvasively in the time
      (baroreflex slope, BRS) and frequency domains (alpha index and systolic arterial
      pressure-RR interval transfer gain) as well as using an exogenous autoregressive
      causal model (A.XAR); carotid mechanical properties were estimated by ultrasound.
      The link between mechanical measures and spontaneous baroreflex indices was
      explored by multivariate analysis and linear modeling. RESULTS: Participants were
      divided into five groups according to age decades. With advancing age we observed
      a decrease in spontaneous baroreflex indices (BRS from 31.2 to 16.3; alpha index
      from 27.4 to 13.6; RR-SAP gain at high frequency from 31 +/- 3.0 to 14 +/- 3.0
      ms/mmHg all P < 0.001) and increase in carotid intima-media thickness (IMT: from
      0.53 to 0.69 mm; P < 0.001) and stiffness (local wave speed: from 4.0 to 6.9 m/s;
      both P < 0.001). A significant correlation was found between spontaneous indices
      of baroreflex sensitivity and carotid mechanical properties, particularly wave
      speed (r = -0.328, P < 0.001). After adjusting for age and sex, a significant
      correlation remained between RR-SAP gain and wave speed and between A.XAR and
      IMT. Factor analysis and automatic linear modeling confirmed the observation that
      mechanical carotid properties are strong predictors of the age-related reduction
      of spontaneous baroreflex. CONCLUSION: A significant correlation between
      spontaneous baroreflex indices and local carotid mechanical properties supports
      the idea that they should be considered in the physiology of baroreflex
      regulation.

PMID- 22871888
TI  - The predictive ability of blood pressure in elderly trial patients.
AB  - OBJECTIVES: To assess the impact of the blood pressure (BP) profile on
      cardiovascular risk in the Medical Research Council (UK) elderly trial;
      investigate whether the effects of hypertensive drugs in reducing event rates are
      solely a product of systolic pressure reduction. METHODS: Using longitudinal BP
      data from 4396 hypertensive patients, the general trend over time was estimated
      using a first-stage multilevel model. We then investigated how BP acted alongside
      other BP-related covariates in a second-stage 'time-to-event' statistical model,
      assessing risk for stroke events and coronary heart disease (CHD). Differences in
      outcome prediction between diuretic, beta-blocker and placebo treatment arms were
      investigated. RESULTS: The beta-blocker arm experienced comparatively poor
      control of current SBP, episodic peaks and variability in BP levels. After
      adjusting for the mean level, variability in SBP over time was significant: risk
      ratio was 1.15 [95% confidence interval (CI): 1.01-1.31] across all patients for
      stroke events. The risk ratio for current SBP was 1.36 (95% CI: 1.16-1.58).
      Current DBP and variability in DBP also predicted stroke independently: risk
      ratios was 1.43 and 1.18, respectively. The risk factors exhibited weaker
      associations with CHD risk; only the highest measured value and variability in
      SBP showed a statistically significant association: risk ratios were 1.26 and
      1.16, respectively. CONCLUSION: Individual risk characterization could be
      augmented with additional prognostic information, besides current SBP, including
      current diastolic pressure, temporal variability over and above general trends
      and historical measurements.

PMID- 22871889
TI  - MWF rats with spontaneous albuminuria inherit a reduced efficiency of nephron
      induction during early nephrogenesis in comparison to SHR rats.
AB  - OBJECTIVES: A congenital nephron deficit has been linked to the progression of
      arterial hypertension and to the development of chronic kidney disease. The
      Munich Wistar Fromter (MWF) inbred rat develops hypertension, progressive
      albuminuria, and exhibits an inherited nephron deficit of about 27% compared to
      spontaneously hypertensive rats (SHRs) with low-grade albuminuria. Introgression
      of rat chromosome (RNO)6 from SHRs into MWF rats markedly suppresses albuminuria
      and abolishes the nephron deficit in 4-week-old MWF-6 rats. Differences in early
      nephrogenesis may account for the nephron deficit in MWF rats. METHODS: We
      compared ureteric bud branching morphogenesis and nephron induction in E15.5
      E16.0 stage-matched rat embryos between MWF rats, SHRs, and consomic MWF-6 rats.
      RESULTS: Comparative analysis of three-dimensional reconstructions of the
      ureteric bud tree suggested normal qualitative branching morphogenesis.
      Surprisingly, the number of ureteric bud tips was higher in MWF rats compared to
      SHRs (+22%; P = 0.004). However, the nephron number induced per ureteric bud tip
      was markedly lower in MWF rats compared to SHRs (-46%; P < 0.0001). This deficit
      was partially corrected in MWF-6 rats (+18% vs. MWF; P = 0.02). In gene
      expression analysis of 59 candidate genes involved in kidney development,
      hepatocyte growth factor (Hgf) gene expression was significantly reduced in
      embryonic kidneys of MWF and MWF-6 rats (approximately -70%; P < 0.004) compared
      to SHRs. CONCLUSIONS: These results suggest a reduced efficiency of nephron
      induction in MWF rats during the early stages of nephrogenesis that is partially
      dependent on genetic loci on RNO6. In addition, Hgf that maps to RNO4 may
      represent an interesting candidate gene that contributes to the nephron deficit
      in MWF rats.

PMID- 22871890
TI  - Genes and environment:  novel, functional polymorphism in the human cathepsin L
      (CTSL1) promoter disrupts a xenobiotic response element (XRE) to alter
      transcription and blood pressure.
AB  - BACKGROUND: Cathepsin L (CTSL1) catalyzes the formation of peptides that
      influence blood pressure (BP). Naturally occurring genetic variation or targeted
      ablation of the Ctsl1 locus in mice yield cardiovascular pathology. Here, we
      searched for genetic variation across the human CTSL1 locus and probed its
      functional effects, especially in the proximal promoter. METHODS AND RESULTS:
      Systematic polymorphism discovery by re-sequencing across CTSL1 in 81 patients
      uncovered 38 genetic variants, five of which were relatively common (MAF >5%),
      creating a single linkage disequilibrium block in multiple biogeographic
      ancestries. One of these five common variants lay in a functional domain of the
      gene: promoter C-171A (rs3118869), which disrupts a predicted xenobiotic response
      element (XRE; match C>A). In transfected CTSL1 promoter/luciferase reporter
      plasmids, C-171A allele influenced transcription (C>A, P = 3.36E-6), and
      transcription was also augmented by co-exposure to the aryl hydrocarbon receptor
      (AHR) complex (AHR:ARNT) in the presence of their ligand dioxin (P = 6.81E-8);
      allele (C vs. A) and AHR:ARNT/dioxin stimulus interacted to control gene
      expression (interaction P = 0.033). Endogenous Ctsl1, Ahr, and Arnt transcripts
      were present in chromaffin cells. Promoter functional C-171A genotype also
      predicted hypertension (P = 1.0E-3), SBP (P = 4.0E-4), and DBP (P = 3.0E-3), in
      an additive pattern for diploid genotypes (A/A > C/A > C/C) in 868 patients, and
      the results were extended by validation analysis into an independent population
      sample of 986 patients. CONCLUSION: We conclude that common genetic variation in
      the proximal CTSL1 promoter, especially at position C-171A, is functional in
      cells, and alters transcription so as to explain the association of CTSL1 with BP
      in vivo. At the XRE, endogenous genetic variation plus exogenous aryl hydrocarbon
      stimulation interact to control CTSL1 gene expression. These results unveil a
      novel control point whereby heredity and environment can intersect to control a
      complex trait, and point to new transcriptional strategies for intervention into
      transmitter biosynthesis and its cardiovascular consequences.

PMID- 22871891
TI  - Hypertension and vascular calcification:  a vicious cycle?
AB  - It is now well established that hypertension is accompanied by remodeling of the
      arterial wall with significant modifications in extracellular matrix composition
      and in vascular cell phenotype. Some of these changes, particularly elastin
      fragments generation, increased proteases activity and activation of transforming
      growth factor-beta signaling together with deposition of collagen and
      proteoglycans might generate a permissive soil for vascular calcification. On the
      other hand, calcium deposits within large arterial conduits can reduce vessel's
      elasticity and contribute to the generation of blood pressure pattern associated
      with vascular stiffness, namely isolated systolic hypertension. Hence, a
      hypothetical vicious cycle exists between hypertensive arterial damage and
      vascular calcification. Herein, we revised clinical and basic science findings
      supporting this possibility.

PMID- 22871892
TI  - Thresholds for pulse wave velocity, urine albumin creatinine ratio and left
      ventricular mass index using SCORE, Framingham and ESH/ESC risk charts.
AB  - AIMS: Markers of subclinical target organ damage (TOD) increase cardiovascular
      (CV) risk prediction beyond traditional risk factors. We wanted to establish
      thresholds for three markers of TOD based on absolute CV risk in different risk
      chart categories. METHODS AND RESULTS: In a cohort of 1968 healthy patients, we
      measured urine albumin creatine ratio (UACR), pulse wave velocity (PWV), left
      ventricular mass index (LVMI) and traditional risk factors. Patients were
      categorized according to Systemic Coronary Evaluation (SCORE), European Society
      of Hypertension/European Society of Cardiology (ESH/ESC) risk chart and
      Framingham risk score (FRS) and three corresponding endpoints were recorded: CV
      death (SCORE-endpoint), a composite of CV death and nonfatal myocardial
      infarction and stroke (ESH/ESC-endpoint), and a composite that also included
      hospital admissions for ischemic heart disease, heart failure, peripheral
      arterial disease and transient cerebral ischemic attack (FRS-endpoint). During a
      median follow of 12.8 years events totaled 81 SCORE-, 153 ESH/ESC-endpoints and
      280 FRS-endpoints. Thresholds for UACR, PWV and LVMI are presented using 10-year
      risk threshold of more than 5% (SCORE-endpoint), more than 10%(ESH/ESC-endpoint)
      and more than 20%(FRS-endpoint), which indicated high risk and eligibility for
      primary prevention. As an example, the threshold was 0.83 mg/mmol, 13.7  m/s and
      119  g/m for UACR, PWV and LVMI, respectively, for patients at moderate added
      risk according to ESH/ESC risk chart. CONCLUSION: Thresholds for UACR, PVW and
      LVMI based on absolute risk have primarily impact on risk stratification in
      patients with intermediate risk. The thresholds for PWV and LVMI in patients with
      moderate risk according to the ESH/ESC risk chart were similar to currently
      applied thresholds whereas the threshold for UACR was considerable lower than the
      threshold for microalbuminuria.

PMID- 22871893
TI  - Urinary angiotensinogen excretion and ambulatory blood pressure.
AB  - OBJECTIVE: Previous studies have demonstrated that urinary angiotensinogen
      excretion, a biomarker of the intrarenal renin-angiotensin system activity, is
      associated with clinic blood pressure (BP). In the present study, we investigated
      the determinants of urinary angiotensinogen excretion and its associations with
      ambulatory BP. METHODS: The study participants were suspected hypertensive
      patients being off antihypertensive medication for at least 2 weeks and referred
      to our hypertension clinic for 24-h ambulatory BP monitoring. Ambulatory
      hypertension was defined as a 24-h BP of at least 130  mmHg systolic or 80  mmHg
      diastolic. We collected a first morning urine sample for the measurement of
      angiotensinogen by ELISA kits. RESULTS: The 446 participants (mean age 51.7
      years) included 218 (48.9%) men, and 275 (61.7%) patients had ambulatory
      hypertension. In addition to age and sex, 24-h urinary sodium excretion was an
      independent determinant of urinary angiotensinogen-to-creatinine ratio (P =
      0.0008). Urinary angiotensinogen-to-creatinine ratio was 34% (P = 0.04) and 82%
      (P <= 0.0001) higher in tertiles 2 and 3 of 24-h urinary sodium excretion,
      respectively, than in tertile 1. In multivariate analyses, urinary
      angiotensinogen-to-creatinine ratio was significantly and positively associated
      with clinic and ambulatory BP (P <= 0.02) and the prevalence of ambulatory
      hypertension [odds ratio (95% confidence interval) associated with two-time
      increase, 1.24 (1.09-1.39); P = 0.0007]. CONCLUSION: Urinary angiotensinogen
      excretion is higher with greater urinary sodium excretion, and is associated with
      clinic and ambulatory BP.

PMID- 22871894
TI  - The great myth of office blood pressure measurement.
AB  - Clinical practice guidelines have traditionally recommended manual blood pressure
      (BP) measurement in the office setting as the standard method for diagnosing
      hypertension. In reality, manual BP in routine clinical practice is relatively
      inaccurate, over-diagnoses hypertension by provoking office-induced increases in
      BP and correlates poorly with both the awake ambulatory BP and target organ
      damage. The most recent guidelines recommend 24-h ambulatory BP and home BP for
      diagnosing hypertension. The advent of automated office BP (AOBP) represents a
      third alternative to conventional manual BP measurement, one that maintains the
      role of office BP readings in the diagnosis and management of hypertension. AOBP
      has three basic principles: multiple readings taken using a fully automated
      sphygmomanometer with the patient resting quietly alone. AOBP eliminates office
      induced hypertension such that the cut-point for a normal AOBP is the same as for
      the awake ambulatory BP and home BP. As compared to routine manual office BP,
      AOBP provides more accurate BP readings, is more consistent during repeated
      office visits and in different settings and correlates better with both the awake
      ambulatory BP and target organ damage. The advantages of AOBP over manual BP
      measurement support its use in routine clinical practice.

PMID- 22871895
TI  - Blood pressure and risk of cardiovascular diseases in type 2 diabetes:  further
      findings from the Swedish National Diabetes Register (NDR-BP II).
AB  - OBJECTIVES: Estimate risks of coronary heart disease (CHD), stroke and
      cardiovascular disease (CVD) with updated mean systolic (SBP) and diastolic (DBP)
      blood pressure in an observational study of patients with type 2 diabetes.
      METHODS: Thirty-five thousand and forty-one patients treated with
      antihypertensive drugs, and 18 512 untreated patients, aged 30-75 years, without
      previous heart failure, followed for 6 years until 2009. RESULTS: In treated
      patients, nonlinear splines for 6-year risk of fatal/nonfatal CHD, stroke and CVD
      by BP as a continuous variable showed a progressive increase with higher SBP from
      140  mmHg and higher, and with DBP from 80  mmHg, with a J-shaped risk curve at
      lowest SBP levels, but not obviously at lowest DBP levels. Analysing intervals of
      SBP with 130-134  mmHg as reference at Cox regression, adjusted hazard ratios
      (HR) for fatal/nonfatal CHD, stroke and CVD with at least 140  mmHg were 1.22
      [95% confidence interval (CI): 1.08-1.39], 1.43 (1.18-1.72), 1.26 (1.13-1.41),
      all P < 0.001. HR with 115-129 and 135-139  mmHg were nonsignificant, whereas
      increased with 100-114  mmHg, 1.96 (P < 0.001), 1.75 (P = 0.02), 2.08 (P <
      0.001), respectively. With DBP 75-79  mmHg as reference, adjusted HR for
      fatal/nonfatal CHD, stroke and CVD with DBP 80-84  mmHg were 1.42 (1.26-1.59),
      1.46 (1.24-1.72), 1.39 (1.26-1.53), all P < 0.001. Corresponding HR with DBP at
      least 85  mmHg were 1.70 (1.50-1.92), 2.35 (1.99-2.77), 1.87 (1.69-2.07), all P <
      0.001. Corresponding HR with DBP 60-69 and 70-74  mmHg were nonsignificant. The
      picture was similar in 7059 patients with previous CVD and in untreated patients.
      CONCLUSION: BP around 130-135/75-79  mmHg showed lower risks of cardiovascular
      diseases in patients with type 2 diabetes.

PMID- 22871896
TI  - Weakly nonlinear analysis of symmetry breaking in cell polarity models.
AB  - Spontaneous symmetry breaking leading to polarization of the cell is a key step
      initiating many morphogenetic processes. In addition to experimental studies,
      model-based theoretical description helps to understand the conditions and
      limitations of this process. Such description is limited usually to linear
      stability analysis supplied by the numerical simulations to establish the
      dependence of the polarization dynamics on the model parameters. Here we describe
      the application of a powerful weakly nonlinear analysis method to a minimalistic
      model characterized by the conservation of mass of the protein governing the
      polarization dynamics.

PMID- 22871897
TI  - Correlation versus agreement in two methods for urinary protein quantification in
      lupus nephritis.

PMID- 22871898
TI  - Gastric intestinal metaplasia revisited: function and regulation of CDX2.
AB  - Intestinal metaplasia of the stomach is a preneoplastic lesion that appears
      following Helicobacter pylori infection and confers increased risk for gastric
      cancer development. However, the molecular networks connecting infection to
      lesion formation and the cellular origin of this lesion remain largely unknown. A
      more comprehensive understanding of how intestinal metaplasia arises and is
      maintained will be a major breakthrough towards developing novel therapeutic
      interventions. Furthermore, after ascertaining the pivotal role of CDX2 in
      establishing and maintaining intestinal metaplasia, it becomes important to
      decipher the upstream molecular pathways leading to its ectopic expression. Here,
      we review the pathophysiology of intestinal metaplasia in the context of the
      molecular network involved in its establishment and maintenance, with emphasis on
      CDX2 function and regulation.

PMID- 22871900
TI  - Nanoparticle flotation collectors III: the role of nanoparticle diameter.
AB  - The ability of polystyrene nanoparticles to promote glass bead flotation was
      measured as a function of nanoparticle diameter. In all cases, smaller
      nanoparticles were more effective flotation collectors, even when compared at
      constant nanoparticle number concentration. The superior performance of smaller
      particles was explained by two mechanisms, acting in parallel. First, smaller
      particles deposit more quickly giving more effective flotation in those cases
      where nanoparticle deposition kinetics is rate determining; the sensitivity of
      nanoparticle deposition rates to particle size was illustrated by kinetic
      measurements on a quartz crystal microbalance silica surface. Second, for a given
      coverage of nanoparticles on the glass beads, the mean distance between
      neighboring nanoparticle surfaces decreases with particle diameter. We propose
      that the expansion of the three phase contact line, after initial bead/bubble
      attachment, is favored with decreasing the distance between neighboring
      hydrophobic particles.

PMID- 22871899
TI  - A novel approach for detection and classification of mammographic
      microcalcifications using wavelet analysis and extreme learning machine.
AB  - The objective of this paper is to reveal the effectiveness of wavelet based
      tissue texture analysis for microcalcification detection in digitized mammograms
      using Extreme Learning Machine (ELM). Microcalcifications are tiny deposits of
      calcium in the breast tissue which are potential indicators for early detection
      of breast cancer. The dense nature of the breast tissue and the poor contrast of
      the mammogram image prohibit the effectiveness in identifying
      microcalcifications. Hence, a new approach to discriminate the
      microcalcifications from the normal tissue is done using wavelet features and is
      compared with different feature vectors extracted using Gray Level Spatial
      Dependence Matrix (GLSDM) and Gabor filter based techniques. A total of 120
      Region of Interests (ROIs) extracted from 55 mammogram images of mini-Mias
      database, including normal and microcalcification images are used in the current
      research. The network is trained with the above mentioned features and the
      results denote that ELM produces relatively better classification accuracy (94%)
      with a significant reduction in training time than the other artificial neural
      networks like Bayesnet classifier, Naivebayes classifier, and Support Vector
      Machine. ELM also avoids problems like local minima, improper learning rate, and
      over fitting.

PMID- 22871901
TI  - Spin coherence generation and detection in spherical nanocrystals.
AB  - A theoretical description of electron spin orientation and detection by short
      optical pulses is proposed for ensembles of singly charged semiconductor
      nanocrystals. The complex structure of the valence band in spherical nanocrystals
      is taken into account. We demonstrate that the direction of electron spin
      injected by the pump pulse depends on both the pump pulse helicity and the pump
      pulse power. It is shown that a train of optical pulses can lead to the complete
      orientation of the resident electron spin. The microscopic theory of the spin
      Faraday, Kerr and ellipticity effects is developed and the spectral sensitivity
      of these signals is discussed. We show that under periodic pumping pronounced
      mode-locking of electron spins takes place and manifests itself as significant
      spin signals at negative delays between pump and probe pulses.

PMID- 22871902
TI  - Evaluating the effectiveness of the US Navy and Marine Corps Tobacco Policy: an
      assessment of secondhand smoke exposure in US Navy submariners.
AB  - OBJECTIVE: To evaluate the effectiveness of the US Navy and Marine Corps tobacco
      policy in protecting submariners from secondhand smoke (SHS) by determining if
      non-tobacco users experienced a significant increase in urinary cotinine levels
      at sea when compared with in port levels. METHODS: From February to August 2009,
      634 volunteers recruited from nine US Navy submarines completed a survey to
      collect demographic data, information on tobacco use and pre-deployment exposure
      to SHS. Non-tobacco users (n=239) were requested to provide two urine samples
      (pre-deployment and while at sea) to quantify exposure to SHS using urinary
      cotinine as a biomarker. Matched samples were analysed using liquid
      chromatography-tandem mass spectrometry. RESULTS: Overall, deployed cotinine
      levels were 2.1 times the in port levels in non-tobacco using submariners (95% CI
      1.8 to 2.4, p<0.001, n=197). A significant increase in deployed urinary cotinine
      levels was found aboard six of nine submarines (p<0.05). A subgroup of
      submariners (n=91) who reported no SHS exposure within 10 days prior to in port
      cotinine sampling had deployed cotinine levels 2.7 times the in port levels (95%
      CI 2.2 to 3.3, p<0.001). Applying a 4.5:1 urine cotinine to serum cotinine
      correction factor, submariners' deployed geometric means are similar to recent US
      male population values at the 75th percentile. CONCLUSIONS: This study provides
      evidence that non-tobacco using submariners were exposed to SHS. Exposure was
      seen in all submarine classes and was not limited to personnel working in
      proximity to the smoking area. The existing policy was inadequate to protect non
      smokers from exposure to SHS and required revision. As a result of a policy
      review, informed by this study, smoking below decks was banned aboard all US Navy
      submarines effective 31 December 2010.

PMID- 22871903
TI  - A heteropentanuclear oxalato-bridged [Re(IV)4Gd(III)] complex: synthesis, crystal
      structure and magnetic properties.
AB  - The compound (NBu(4))(5)[Gd(III){Re(IV)Br(4)(MU-ox)}(4)(H(2)O)].H(2)O (1), with
      intramolecular antiferromagnetic coupling, is the first Re(iv) system
      incorporating a 4f ion.

PMID- 22871904
TI  - Teleconferencing as a source of social support for older spousal caregivers:
      initial explorations and recommendations for future research.
AB  - Teleconferencing is increasingly being used as a medium of delivering social
      support for dementia caregivers. Further direction is required from pilot studies
      before the optimal clinical service can be delivered. Following a 6-week pilot
      support group for spousal caregivers, delivered via teleconferencing software, we
      interviewed 8 participants for their feedback. Semi-structured interviews were
      conducted and analyzed using grounded theory analysis. Themes of "group
      processes" and "barriers," containing subcategories of "functions of the group,"
      "responsibilities of facilitators," and "barriers to communication" were
      discussed. According to caregivers, successful teleconferencing support groups
      should acknowledge the caregiver as the dementia expert, allow participants to
      meet before the deployment of the support group, provide active facilitation and
      leadership via the researcher, employ user-friendly technologies, and facilitate
      for the group to self-maintain following the pilot deployment period. These
      issues should be taken into consideration when designing future teleconferencing
      applications for caregivers.

PMID- 22871905
TI  - Feasibility and perception of the impact from aerobic exercise in older adults
      with Alzheimer's disease.
AB  - BACKGROUND: The subjective experience of participating in aerobic exercise is
      unknown in Alzheimer's disease (AD). OBJECTIVE: The purpose of this study was to
      understand the subjective perceptions of the feasibility and impact of a 6-month,
      moderate-intensity aerobic exercise intervention by older adults with AD and
      their family caregivers. METHODS: Ten older adults with AD who completed the
      intervention and their family caregivers participated in four focus group
      interviews. RESULTS: Four converging themes were identified: "There was no
      perceived positive change in cognitive symptoms," "The 6-month exercise program
      was socially rewarding," "The 6-month exercise program increased physical
      strength," and "Participation in aerobic exercise was a positive experience."
      Family caregivers further identified two additional themes: "The exercise program
      led to improved attitude in older adults with AD" and "The exercise program
      reduced caregiver stress." DISCUSSION: Aerobic exercise is a feasible and well
      perceived intervention for older adults with AD and their family caregivers.

PMID- 22871907
TI  - Toward a more nuanced perception of Alzheimer's disease: designing and testing a
      campaign advertisement.
AB  - Starting point of this study was the assumption that Alzheimer's disease is made
      worse for the person who has the disease by the negative regard in which the
      illness is held by society. The aim was to test by means of a campaign
      advertisement whether more nuanced counterframes could have an impact while
      remaining credible and comprehensible to the public. A sample of thousand people
      living in Belgium evaluated the campaign in an experimental design. This revealed
      that all the versions tested achieved a high average evaluation. The ad in which
      the heading referred to the fear of death and degeneration was judged to be most
      attention-grabbing, easier to understand, and more credible than the alternative
      heading with the idea that someone with Alzheimer's could still enjoy playing
      cards. Together, these findings provided a basis for the use of counterframes to
      generating a more nuanced image of Alzheimer's disease.

PMID- 22871906
TI  - Nonamnestic presentations of early-onset Alzheimer's disease.
AB  - Early-onset Alzheimer's disease (EOAD) beginning before the age of 65 may differ
      from late-onset AD (LOAD) in clinical course and frequency of nonamnestic
      presentations. In a 10-year retrospective review, 125 patients with EOAD,
      diagnosed clinically and verified by functional neuroimaging, were compared with
      56 patients with LOAD and further classified depending on predominant cognitive
      difficulty on presentation. Eighty (64%) of the patients with EOAD had a
      nonamnestic presentation, compared with only 7 (12.5%) of the patients with LOAD.
      Compared with LOAD, the patients with EOAD had a shorter duration with lower Mini
      Mental State Examination scores. The neuroimaging reports among the patients with
      EOAD showed more hippocampal atrophy with an amnestic presentation, more left
      parietal changes with impaired language presentations, and more right parietal
      and occipital changes with impaired visuospatial presentations. These findings
      indicate that EOAD differs from LOAD in a more aggressive course and in having
      predominantly nonamnestic presentations that vary in neuropathological location.

PMID- 22871908
TI  - Impact of fall-related behaviors as risk factors for falls among the elderly
      patients with dementia in a geriatric facility in Japan.
AB  - The purpose of this study was to clarify potential fall-related behaviors as fall
      risk factors that may predict the potential for falls among the elderly patients
      with dementia at a geriatric facility in Japan. This study was conducted from
      April 2008 to May 2009. A baseline study was conducted in April 2008 to evaluate
      Mini-Mental State Examination, Physical Self-Maintenance Scale, fall-related
      behaviors, and other factors. For statistical analysis, paired t test and
      logistic analysis were used to compare each item between fallers and nonfallers.
      A total of 135 participants were followed up for 1 year; 50 participants (37.04%)
      fell during that period. Results of multiple logistic regression analysis showed
      that the total score for fall-related behaviors was significantly related to
      falls. It was suggested that 11 fall-related behaviors may be effective
      indicators to predict falls among the elderly patients with dementia.

PMID- 22871909
TI  - An fMRI study of prefrontal cortical function in subcortical ischemic vascular
      cognitive impairment.
AB  - Functional magnetic resonance imaging (fMRI) technology has not been used to
      investigate the frontal lobe function of subcortical ischemic vascular cognitive
      impairment (SIVCI). In this study 11 healthy elderly controls, 12 patients with
      subcortical ischemic vascular cognitive impairment no dementia (SIVCIND), and 12
      patients with subcortical ischemic vascular dementia (SIVD) underwent fMRI
      examination on a SIEMENS Trio 3.0 Tesla scanner during Stroop task performance.
      Compared to the controls, participants with SIVCIND showed markedly increased
      activation in prefrontal cortex. By contrast, participants with SIVD exhibited
      decreased fMRI responses in the regions described above. A close correlation was
      found between the cognitive score in Montreal Cognitive Assessment test and the
      activation area of frontal and parietal lobule of patients with SIVD. Our results
      suggest that the alterations of cortical activation in SIVCI were bidirectional.
      There is a prefrontal dysfunction in SIVD and a compensation in SIVCIND. These
      findings might help guide a clinical differentiation among normal controls,
      SIVCIND, and SIVD.

PMID- 22871910
TI  - Sex differences in selecting between food and cocaine reinforcement are mediated
      by estrogen.
AB  - Cocaine-dependent women, relative to their male counterparts, report shorter
      cocaine-free periods and report transiting faster from first use to entering
      treatment for addiction. Similarly, preclinical studies indicate that female
      rats, particularly those in the estrus phase of their reproductive cycle, show
      increased operant responding for cocaine under a wide variety of schedules.
      Making maladaptive choices is a component of drug dependence, and concurrent
      reinforcement schedules that examine cocaine choice offers an animal model of the
      conditions of human drug use; therefore, the examination of sex differences in
      decision-making may be critical to understanding why women display a more severe
      profile of cocaine addiction than men. Accordingly, we assessed sex and estrous
      cycle differences in choice between food (45 mg grain pellets) and intravenous
      cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely
      cycling), and ovariectomized (OVX) females treated with either estrogen benzoate
      (EB; 5 MUg per day) or vehicle. At both cocaine doses, intact female rats choose
      cocaine over food significantly more than male rats. However, the estrous cycle
      did not impact the level of cocaine choice in intact females. Nevertheless, OVX
      females treated with vehicle exhibited a substantially lower cocaine choice
      compared with those receiving daily EB or to intact females. These results
      demonstrate that intact females have a greater preference for cocaine over food
      compared with males. Furthermore, this higher preference is estrogen-dependent,
      but does not vary across the female reproductive cycle, suggesting that ovarian
      hormones regulate cocaine choice. The present findings indicate that there is a
      biological predisposition for females to forgo food reinforcement to obtain
      cocaine reinforcement, which may substantially contribute to women experiencing a
      more severe profile of cocaine addiction than men.

PMID- 22871911
TI  - Seizure susceptibility and epileptogenesis in a rat model of epilepsy and
      depression co-morbidity.
AB  - Although a strong co-morbidity exists clinically between epilepsy and depression,
      the cause of this co-morbidity remains unknown, and a valid animal model is
      crucial for the identification of underlying mechanisms and the development of a
      screening tool for novel therapies. Although some rodent models of epilepsy have
      been reported to display behaviors relevant to affective disorders, the seizure
      susceptibility of animals prone to depression-like behavior has not been
      characterized. Toward this end, we assessed several forms of seizure sensitivity
      and epileptogenesis in rats selectively bred for vulnerability (Swim Lo-Active;
      SwLo) or resilience (Swim High-Active; SwHi) to depression-like phenotypes. The
      SwLo rats exhibit decreased motor activity in a swim test and other depression
      like phenotypes, whereas the SwHi rats display increased motor activity in a swim
      test. SwLo rats exhibited a decreased latency to limbic motor seizures following
      acute pilocarpine administration in the absence of differences in pilocarpine
      pharmacokinetics, and also had a decreased threshold to tonic seizures induced by
      electroshock. Approximately half of the SwLo rats, but none of the SwHi rats, had
      spontaneous limbic motor seizures 5 weeks following pilocarpine-induced status
      epilepticus. While the number of stimulations required to achieve full amygdala
      and hippocampal electrical kindling were similar in the two rat lines, SwLo rats
      had a lower final hippocampal kindling threshold and more wet dog shakes during
      both amygdala and hippocampal kindling. Combined, these results indicate that
      SwLo rats are a model of epilepsy and depression co-morbidity that can be used
      for investigating underlying neurobiological and genetic mechanisms and screening
      novel therapeutics.

PMID- 22871912
TI  - White matter integrity in highly traumatized adults with and without post
      traumatic stress disorder.
AB  - Prior structural imaging studies of post-traumatic stress disorder (PTSD) have
      observed smaller volumes of the hippocampus and cingulate cortex, yet little is
      known about the integrity of white matter connections between these structures in
      PTSD samples. The few published studies using diffusion tensor imaging (DTI) to
      measure white matter integrity in PTSD have described individuals with focal
      trauma rather than chronically stressed individuals, which limits generalization
      of findings to this population; in addition, these studies have lacked
      traumatized comparison groups without PTSD. The present DTI study examined
      microstructural integrity of white matter tracts in a sample of highly
      traumatized African-American women with (n=25) and without (n=26) PTSD using a
      tract-based spatial statistical approach, with threshold-free cluster
      enhancement. Our findings indicated that, relative to comparably traumatized
      controls, decreased integrity (measured by fractional anisotropy) of the
      posterior cingulum was observed in participants with PTSD (p<0.05). These
      findings indicate that reduced microarchitectural integrity of the cingulum, a
      white matter fiber that connects the entorhinal and cingulate cortices, appears
      to be associated with PTSD symptomatology. The role of this pathway in problems
      that characterize PTSD, such as inadequate extinction of learned fear, as well as
      attention and explicit memory functions, are discussed.

PMID- 22871913
TI  - Clozapine-induced locomotor suppression is mediated by 5-HT2A receptors in the
      forebrain.
AB  - The need for safer, more effective therapeutics for the treatment of
      schizophrenia is widely acknowledged. To optimally target novel
      pharmacotherapies, in addition to establishing the mechanisms responsible for the
      beneficial effects of antipsychotics, the pathways underlying the most severe
      side effects must also be elucidated. Here we investigate the role of serotonin
      2A (5-HT(2A)), serotonin 2C (5-HT(2C)), and dopamine 2 receptors (D2) in
      mediating adverse effects associated with canonical first- and second-generation
      antipsychotic drugs in mice. Wild-type (WT) and 5-HT(2A) knockout (KO) mice
      treated with haloperidol, clozapine, and risperidone were assessed for locomotor
      activity and catalepsy. WT mice showed a marked reduction in locomotor activity
      following acute administration of haloperidol and high-dose risperidone, which
      was most likely secondary to the severe catalepsy caused by these compounds.
      Clozapine also dramatically reduced locomotor activity, but in the absence of
      catalepsy. Interestingly, 5-HT(2A) KO mice were cataleptic following haloperidol
      and risperidone, but did not respond to clozapine's locomotor-suppressing
      effects. Restoration of 5-HT(2A) expression to cortical glutamatergic neurons re
      instated the locomotor-suppressing effects of clozapine in the open field. In
      sum, we confirm that haloperidol and risperidone caused catalepsy in rodents,
      driven by strong antagonism of D2. We also demonstrate that clozapine decreases
      locomotor activity in a 5-HT(2A)-dependent manner, in the absence of catalepsy.
      Moreover, we show that it is the cortical population of 5-HT(2A) that mediate the
      locomotor-suppressing effects of clozapine.

PMID- 22871914
TI  - White matter abnormalities in pediatric obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling
      illness with onset generally in childhood or adolescence. Although white matter
      deficits have been implicated in the neurobiology of OCD, few studies have been
      conducted in pediatric patients when the brain is still developing and have
      examined their functional correlates. In this study, 23 pediatric OCD patients
      and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex,
      age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE
      system and a brief neuropsychological battery tapping executive functions.
      Patient symptom severity was assessed using the Children's Yale-Brown Obsessive
      Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater
      fractional anisotropy compared to matched controls in the left dorsal cingulum
      bundle, splenium of the corpus callosum, right corticospinal tract, and left
      inferior fronto-occipital fasciculus. There were no regions of significantly
      lower fractional anisotropy in patients compared to controls. Higher fractional
      anisotropy in the splenium was significantly correlated with greater obsession
      severity on the CY-BOCS in the subgroup of psychotropic drug-naive patients.
      Among patients, there was a significant association between greater fractional
      anisotropy in the dorsal cingulum bundle and better performance on measures of
      response inhibition and cognitive control. The overall findings suggest a pattern
      of greater directional coherence of white matter tracts in OCD very early in the
      course of illness, which may serve a compensatory mechanism, at least for
      response inhibition functions typically subserved by the cingulum bundle.

PMID- 22871915
TI  - Preclinical evaluation of reconsolidation blockade by clonidine as a potential
      novel treatment for posttraumatic stress disorder.
AB  - Exposure to traumatic events can lead to posttraumatic stress disorder (PTSD).
      Current PTSD treatments typically only produce partial improvement. Hence, there
      is a need for preclinical research to identify new candidate drugs and to develop
      novel therapeutic approaches. Animal studies have indicated that fear memories
      can be weakened by blocking restabilization after retrieval, a process known as
      reconsolidation. Furthermore, evidence suggests that there are important
      alterations of the noradrenergic system in PTSD, and hence it may be of interest
      to study drugs that target this pathway. Here, we investigated the efficacy of
      clonidine, an alpha2-adrenoreceptor agonist, to block reconsolidation in an
      animal model of persistent traumatic memories. Using an auditory fear
      conditioning paradigm in rats, we tested the efficacy of clonidine to weaken fear
      memory retention when administered systemically after retrieval. We evaluated
      dosage, number of treatments, and specificity in reconsolidation blockade. We
      found that postretrieval administration of clonidine disrupts fear-related
      memories in a dose-dependent manner and that two treatments are sufficient for
      maximal memory impairment. Furthermore, we determined that this effect is long
      lasting and specific to reconsolidation processes as shown by the selectivity to
      affect reactivated memories and the absence of spontaneous recovery and of
      postreactivation short-term memory impairment. Our results demonstrate the
      efficacy of systemic administration of clonidine following retrieval to
      persistently disrupt fear memory retention through reconsolidation blockade. This
      study provides important preclinical parameters for future therapeutic strategies
      involving clonidine to block reconsolidation as a novel treatment for PTSD
      symptoms.

PMID- 22871916
TI  - The impact of gabapentin administration on brain GABA and glutamate
      concentrations: a 7T 1H-MRS study.
AB  - Gamma-aminobutyric acid (GABA) and glutamate are implicated in numerous
      neuropsychiatric and substance abuse conditions, but their spectral overlap with
      other resonances makes them a challenge to quantify in humans. Gabapentin,
      marketed for the treatment of seizures and neuropathic pain, has been shown to
      increase in vivo GABA concentration in the brain of both rodents and humans.
      Gabapentin effects on glutamate are not known. We conducted a gabapentin (900 mg)
      challenge in healthy human subjects to confirm and explore its effects on GABA
      and glutamate concentrations, respectively, and to test the ability of single
      voxel localized proton magnetic resonance spectroscopy (1H-MRS) to reliably
      measure GABA and glutamate in the visual cortex at the ultra-high magnetic field
      of 7 Tesla. Reproducibility of GABA and glutamate measurements was determined in
      a comparison group without drug twice within day and 2 weeks apart. Although GABA
      concentration changes were small both within day (average 5.6%) and between day
      (average 4.8%), gabapentin administration was associated with an average increase
      in GABA concentration of 55.7% (6.9-91.0%). Importantly, drug-induced change in
      GABA levels was inversely correlated to the individual's baseline GABA level
      (R2=0.72). Mean glutamate concentrations did not change significantly with or
      without drug administration. In conclusion, localized 1H-MRS at 7 Tesla can be
      successfully applied to the measurement of GABA concentration and is sensitive to
      acute drug-induced changes in cortical GABA. Whether baseline GABA concentrations
      predict clinical efficacy of gabapentin is an area worthy of exploration.

PMID- 22871917
TI  - Differences in FKBP51 regulation following chronic social defeat stress correlate
      with individual stress sensitivity: influence of paroxetine treatment.
AB  - Various clinical studies have identified FK506-binding protein 51 (FKBP51) as a
      target gene involved in the development of psychiatric disorders such as
      depression. Furthermore, FKBP51 has been shown to affect glucocorticoid receptor
      signaling by sensitivity modulation and it is implicated in stress reactivity as
      well as in molecular mechanisms of stress vulnerability and resilience. We
      investigated the physiological, behavioral, and neuroendocrine parameters in an
      established chronic stress model both directly after stress and after a recovery
      period of 3 weeks and also studied the efficacy of paroxetine in this model. We
      then examined FKBP51 mRNA levels in the dorsal and ventral part of the
      hippocampus and correlated the expression to behavioral and endocrine parameters.
      We show robust chronic stress effects in physiological, behavioral, and
      neuroendocrine parameters, which were only slightly affected by paroxetine
      treatment. On the contrary, paroxetine led to a disruption of the neuroendocrine
      system. FKBP51 expression was significantly increased directly after the stress
      period and correlated with behavioral and neuroendocrine parameters. Taken
      together, we were able to further elucidate the role of FKBP51 in the mechanisms
      of stress resilience and vulnerability, especially with respect to behavioral and
      neuroendocrine parameters. These findings strongly support the concept of FKBP51
      as a marker for glucocorticoid receptor sensitivity and its involvement in the
      development of psychiatric disorders.

PMID- 22871918
TI  - Upregulation of nerve growth factor in central amygdala increases sensitivity to
      opioid reward.
AB  - The rewarding properties of opioids are essential driving force for compulsive
      drug-seeking and drug-taking behaviors in the development of opioid-mediated drug
      addiction. Prior drug use enhances sensitivity to the rewarding effects of
      subsequently used drugs, increasing vulnerability to relapse. The molecular
      mechanisms underlying this reward sensitization are still unclear. We report here
      that morphine that induced reward sensitization, as demonstrated by reinstatement
      of the behavior of conditioned place preference (CPP) with sub-threshold priming
      morphine, epigenetically upregulated the output activity of Ngf encoding the
      nerve growth factor (NGF) by increasing histone H4 acetylation in the rat central
      nucleus of the amygdala (CeA). NGF locally infused into the CeA mimicked the
      morphine effect in inducing new functional delta-opioid receptor (DOR) that was
      required for the reward sensitization, and morphine-induced reward sensitization
      was inhibited by blocking NGF receptor signaling in the CeA. Histone deacetylase
      inhibitors that increased the acetylation level at the Ngf promoter and NGF
      expression in the CeA also induced reward sensitization in a CeA NGF signaling-
      and DOR-dependent manner. Furthermore, CeA-applied NGF substituted prior morphine
      to induce reward sensitization in naive rats and also substituted priming
      morphine to reinstate the CPP induced by prior morphine. Thus, epigenetic
      upregulation of NGF activity in the CeA may promote the behavior of opioid reward
      and increase the sensitivity to the rewarding effect of subsequent opioids, a
      potentially important mechanism in drug addiction.

PMID- 22871920
TI  - Genetics and molecular basis of human peroxisome biogenesis disorders.
AB  - Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of
      autosomal recessive disorders comprised of two clinically distinct subtypes: the
      Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia
      punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14
      different PEX genes, which encode proteins involved in peroxisome assembly and
      proliferation. Thirteen of these genes are associated with ZSS disorders. The
      genetic heterogeneity among PBDs and the inability to predict from the
      biochemical and clinical phenotype of a patient with ZSS which of the currently
      known 13 PEX genes is defective, has fostered the development of different
      strategies to identify the causative gene defects. These include PEX cDNA
      transfection complementation assays followed by sequencing of the thus identified
      PEX genes, and a PEX gene screen in which the most frequently mutated exons of
      the different PEX genes are analyzed. The benefits of DNA testing for PBDs
      include carrier testing of relatives, early prenatal testing or preimplantation
      genetic diagnosis in families with a recurrence risk for ZSS disorders, and
      insight in genotype-phenotype correlations, which may eventually assist to
      improve patient management. In this review we describe the current status of
      genetic analysis and the molecular basis of PBDs.

PMID- 22871919
TI  - Electrophysiological effects of repeated administration of agomelatine on the
      dopamine, norepinephrine, and serotonin systems in the rat brain.
AB  - Agomelatine is a melatonergic MT1/MT2 agonist and a serotonin (5-HT) 5-HT(2C)
      antagonist. The effects of 2-day and 14-day administration of agomelatine were
      investigated on the activity of ventral tegmental area (VTA) dopamine (DA), locus
      coeruleus (LC) norepinephrine (NE), and dorsal raphe nucleus (DRN) 5-HT neurons
      using in vivo electrophysiology in rats. The 5-HT(1A) transmission was assessed
      at hippocampus CA3 pyramidal neurons. After a 2-day regimen of agomelatine (40
      mg/kg/day, i.p.), an increase in the number of spontaneously active VTA-DA
      neurons (p<0.001) and in the firing rate of LC-NE neurons (p<0.001) was observed.
      After 14 days, the administration of agomelatine induced an increase in: (1) the
      number of spontaneously active DA neurons (p<0.05), (2) the bursting activity of
      DA neurons (bursts/min, p<0.01 and percentage of spikes occurring in bursts,
      p<0.05), (3) the firing rate of DRN-5-HT neurons (p<0.05), and (4) the tonic
      activation of postsynaptic 5-HT(1A) receptors located in the hippocampus. The
      increase in 5-HT firing rate was D2 dependent, as it was antagonized by the D2
      receptor antagonist paliperidone. The enhancement of NE firing was restored by
      the 5-HT(2A) receptor antagonist MDL-100,907 after the 14-day regimen. All the
      effects of agomelatine were antagonized by a single administration of the
      melatonergic antagonist S22153 (except for the increase in the percentage of
      spikes occurring in burst for DA neurons). The present results suggest that (1)
      agomelatine exerts direct (2 days) and indirect (14 days) modulations of
      monoaminergic neuronal activity and (2) the melatonergic agonistic activity of
      agomelatine contributes to the enhancement of DA and 5-HT neurotransmission.

PMID- 22871922
TI  - The relationship between Helicobacter pylori infection and the effects of
      chemotherapy in patients with advanced or metastatic gastric cancer.
AB  - PURPOSE: Several reports have shown a better prognosis in gastric cancer patients
      who are positive for Helicobacter pylori (HP) infection compared with negative
      cases. However, there are currently no studies that investigate the relationship
      between HP infection and the effects of chemotherapy in gastric cancer patients.
      In this study, we report the relationship between HP infection and chemotherapy
      effects in patients with advanced or metastatic gastric cancer. METHODS: Sixty
      one patients with advanced or metastatic gastric cancer were enrolled in this
      study. Biopsies were conducted around the tumor site to determine HP status.
      Patients were then treated with combination 5-FU and cisplatin-based
      chemotherapy. And we compared chemotherapy response rate and overall survival
      rate between HP infection group and without HP infection group. RESULTS: Twelve
      of 18 patients with HP infection (66.7 %) and 9 of 42 patients without HP
      infection (21.4 %) showed a partial response to chemotherapy (Chi square P =
      0.001). Patients with HP infection had a median survival time of 13 months (95 %
      CI, 6.9-19.1 months), which was significantly longer than that of patients
      without HP infection (9 months; P = 0.027, log-rank test). CONCLUSIONS: Patients
      with advanced or metastatic gastric cancer with concomitant HP infection had a
      better response to chemotherapy and had an improved overall prognosis compared
      with patients without HP infection. Further studies are warranted to confirm
      these findings.

PMID- 22871921
TI  - Isolation and culture of hippocampal neurons from prenatal mice.
AB  - Primary cultures of rat and murine hippocampal neurons are widely used to reveal
      cellular mechanisms in neurobiology. By isolating and growing individual neurons,
      researchers are able to analyze properties related to cellular trafficking,
      cellular structure and individual protein localization using a variety of
      biochemical techniques. Results from such experiments are critical for testing
      theories addressing the neural basis of memory and learning. However, unambiguous
      results from these forms of experiments are predicated on the ability to grow
      neuronal cultures with minimum contamination by other brain cell types. In this
      protocol, we use specific media designed for neuron growth and careful dissection
      of embryonic hippocampal tissue to optimize growth of healthy neurons while
      minimizing contaminating cell types (i.e. astrocytes). Embryonic mouse
      hippocampal tissue can be more difficult to isolate than similar rodent tissue
      due to the size of the sample for dissection. We show detailed dissection
      techniques of hippocampus from embryonic day 19 (E19) mouse pups. Once
      hippocampal tissue is isolated, gentle dissociation of neuronal cells is achieved
      with a dilute concentration of trypsin and mechanical disruption designed to
      separate cells from connective tissue while providing minimum damage to
      individual cells. A detailed description of how to prepare pipettes to be used in
      the disruption is included. Optimal plating densities are provided for immuno
      fluorescence protocols to maximize successful cell culture. The protocol provides
      a fast (approximately 2 hr) and efficient technique for the culture of neuronal
      cells from mouse hippocampal tissue.

PMID- 22871923
TI  - Mutation distribution in the von Willebrand factor gene related to the different
      von Willebrand disease (VWD) types in a cohort of VWD patients.
AB  - Von Willebrand disease (VWD) is the most common inherited bleeding disorder
      caused by quantitative or qualitative defects of the von Willebrand factor (VWF).
      VWD is classified into three types--type 1 (partial quantitative deficiencies),
      type 2 (qualitative defects) and type 3 (complete deficiency of VWF). In this
      study we explored genotype and phenotype characteristics of patients with VWD
      with the aim of dissecting the distribution of mutations in different types of
      VWD. One hundred fourteen patients belonging to 78 families diagnosed to have VWD
      were studied. Mutation analysis was performed by direct sequencing of the VWF .
      Large deletions were investigated by multiplex ligation-dependent probe
      amplification (MLPA) analysis. The impact of novel candidate missense mutations
      and potential splice site mutations was predicted by in silico assessments. We
      identified mutations in 66 index patients (IPs) (84.6%). Mutation detection rate
      was 68%, 94% and 94% for VWD type 1, 2 and 3, respectively. In total, 68
      different putative mutations were detected comprising 37 missense mutations
      (54.4%), 10 small deletions (14.7%), two small insertions (2.9%), seven nonsense
      mutations (10.3%), five splice-site mutations (7.4%), six large deletions (8.8%)
      and one silent mutation (1.5%). Twenty-six of these mutations were novel.
      Furthermore, in type 1 and type 2 VWD, the majority of identified mutations (74%
      vs. 88.1%) were missense substitutions while mutations in type 3 VWD mostly
      caused null alleles (82%). Genotyping in VWD is a helpful tool to further
      elucidate the pathogenesis of VWD and to establish the relationship between
      genotype and phenotype.

PMID- 22871924
TI  - Associations between osteochondrosis and conformation and locomotive
      characteristics in pigs.
AB  - Conformation and locomotive characteristics (CLC; i.e., leg conformation and gait
      movement patterns) may be associated with osteochondrosis (OC) in pigs.
      Osteochondrosis and CLC increase the risk of premature culling. This study
      investigated whether CLC have an explanatory value, over the previously modeled
      effects of sex, feeding, and housing conditions, on the occurrence and severity
      of OC in several joints and at the animal level. At 154 to 156 d of age, 267 pigs
      were subjectively scored on 9 conformation and 2 locomotive characteristics.
      Scoring was performed on a 9-point linear grading scale. For conformation
      characteristics, score 5 indicated normal conformation and scores 1 and 9
      indicated severe deviations from normal. For the locomotive characteristics,
      score 1 indicated normal locomotion and score 9 indicated severe deviation from
      normal. At 161 to 176 d of age, pigs were slaughtered and joints were dissected
      for macroscopic evaluation of OC status. Results showed that swaying hindquarters
      and a stiffer gait were associated with greater scores for OC in, respectively,
      the femoropatellar (P = 0.018) and tarsocrural joint (P = 0.005), smaller inner
      claws as compared with the outer claws of the front legs was associated with
      lower scores for OC than equally sized claws in the femoropatellar joint (P =
      0.021) and on animal level (P = 0.010), steep and weak pasterns of the front legs
      were associated with greater scores for OC in the elbow joint (P = 0.004) and on
      animal level (P = 0.018), X-shaped hind legs was associated with greater scores
      for OC on animal level (P = 0.037), and steep and weak pasterns of the hind legs
      were associated with lower scores for OC than normal conformation in the
      tarsocrural joint (P = 0.05). This study found several CLC that were associated
      with OC in several joints and at an animal level. This study showed that certain
      CLC might be used as indicators of OC and included in the criteria for selection
      of replacement animals for the breeding herd.

PMID- 22871925
TI  - Effects of feed-borne Fusarium mycotoxins on performance, serum chemistry, and
      intestinal histology of New Zealand White fryer rabbits.
AB  - The objective of the present study was to determine the effects of feeding diets
      containing grains naturally contaminated with Fusarium mycotoxins to fryer
      rabbits. The efficacy of a glucomannan mycotoxin adsorbent (GMA) was also
      examined. Thirty 5-wk-old male New Zealand White rabbits were fed a control diet,
      a contaminated diet, or a contaminated diet + 0.2% GMA for 21 d. Experimental
      diets contained deoxynivalenol (DON; vomitoxin) at a concentration of 0.25, 4.3,
      and 4.9 MUg/g, respectively. Feed intake was measured daily and water intake was
      measured every 3 d. At the end of the feeding period, blood was collected for
      evaluation of serum chemistry and hematology. Visceral organs were excised,
      weighed, and processed for histopathological examination. Body weight gain and
      water intake were greater in rabbits fed the contaminated diet (P = 0.075 and
      0.020, respectively) and those fed the contaminated + GMA diet (P = 0.026 and
      0.002, respectively) compared with controls. Rabbits fed the contaminated + GMA
      diet had significantly increased serum urea concentrations (P = 0.023) and
      decreased serum alkaline phosphatase activity (P = 0.020) compared with controls.
      Increase in BW gain of rabbits fed the contaminated diets was caused by increased
      water consumption. There was no effect (P > 0.05) of diet on relative organ
      weights, but decreased infiltrations with eosinophilic granulocytes were observed
      in different regions of the intestine in rabbits fed the contaminated or the
      contaminated + GMA diet. It was concluded that rabbits could be adversely
      affected by feed-borne Fusarium mycotoxins but appear to be less sensitive than
      other mammalian species. Supplementation with GMA did not reduce many of the
      effects of feed-borne mycotoxins.

PMID- 22871927
TI  - A generic model of growth, energy metabolism, and body composition for cattle and
      sheep.
AB  - A generic daily time-step model of animal growth and metabolism for cattle and
      sheep is described. It includes total BW as well as protein, water, and fat
      components, and also energy components associated with the growth of protein and
      fat, and activity costs. Protein decay is also incorporated, along with the
      energy costs of resynthesising degraded protein. Protein weight is taken to be
      the primary indicator of metabolic state, and fat is regarded as a potential
      source of metabolic energy for physiological processes such as the resynthesis of
      degraded protein. Normal weight is defined as maximum protein and the associated
      fat component so that if the BW of the animal exceeds the normal value, all
      excess weight is in the form of fat. It is assumed that the normal fat fraction
      increases from birth to maturity. There are relatively few parameters, all of
      which have a reasonable physiological interpretation, which helps simplify
      choosing parameters for different animal types and breeds. Simulations for
      growing and mature cattle and sheep in response to varying available ME are
      presented and comparisons with empirical curves reported in the literature for
      body composition are in excellent agreement.

PMID- 22871926
TI  - Determination of the appropriate delivery of prostaglandin F2alpha in the five
      day CO-Synch + controlled intravaginal drug release protocol in suckled beef
      cows.
AB  - The objective of this experiment was to determine if 2 doses of prostaglandin
      F(2alpha) (PGF) administered concurrently at controlled intravaginal drug release
      (CIDR) removal was an efficacious method for delivery of PGF in the 5-d CO-Synch
      + CIDR protocol. Postpartum beef cows (n = 2,465) from 13 herds in 8 states were
      enrolled in the 5-d CO-Synch + CIDR protocol and assigned to receive 2 doses of
      PGF (25 mg/dose) 8 h apart with the initial injection given at CIDR insert
      removal (8h-PGF), 2 doses (25 mg/dose) of PGF delivered in 2 injection sites,
      both administered at CIDR insert removal (Co-PGF), or a single 25-mg dose of PGF
      at CIDR insert removal (1x-PGF). Cows were fixed timed-artificially inseminated
      (FTAI) 72 h after CIDR removal concurrent with GnRH administration. Estrus
      cycling status (54% cyclic) was determined by evaluation of progesterone in 2
      blood samples collected before CIDR insertion. Determination of pregnancy was
      performed by transrectal ultrasonography 39 +/- 0.1 d after FTAI and at least 35
      d after the conclusion of the breeding season. Fixed timed-AI pregnancy rates
      were greater (P < 0.05) for the 8h-PGF (55%) than the 1x-PGF (48%) treatment,
      with the Co-PGF (51%) treatment intermediate and not different (P > 0.10) from
      the other treatments. Contrast analysis demonstrated that cows receiving 50 mg of
      PGF (8h-PGF and Co-PGF) had greater (P < 0.05) FTAI pregnancy rates than those
      receiving 25 mg (1x-PGF). Pregnancy rates to FTAI were greater (P < 0.05) in
      cyclic (55%) than noncyclic (47%) and greater (P < 0.05) in multiparous (>=3 yr
      of age; 54%; n = 1,940) than primiparous cows (40%; n = 525). Luteolysis after
      PGF treatment was assessed in a subset of cows (n = 277) and treatment tended (P
      = 0.09) to affect the proportion of cows having luteolysis. The percentage of
      cows that had luteolysis was least in the 1x-PGF treatment (89%) and greatest in
      the 8h-PGF treatment (97%), with the Co-PGF treatment (94%) being intermediate.
      Breeding season pregnancy rate (88%) did not differ (P > 0.10) among treatments
      but was greater (P < 0.01) in multiparous (90%) than primiparous (78%) cows. In
      summary, 50 mg of PGF was required in the 5-d CO-Synch + CIDR protocol to
      maximize pregnancy rates; however, pregnancy rate did not differ when 50 mg of
      PGF was administered simultaneously with CIDR removal or split with 25 mg
      administered at 0 and 8 h after CIDR removal.

PMID- 22871928
TI  - Effect of calving distribution on beef cattle progeny performance.
AB  - Records collected between 1997 and 2010 were used to determine the effect of
      calving period on heifer (n = 1,019) and steer (n = 771) progeny from the
      Gudmundsen Sandhills Laboratory, Whitman, NE. Progeny were classified as being
      born in the first, second, or third 21-d period of the spring calving season
      within year. Heifer birth BW was lightest (P < 0.01) for heifers born in the
      first period. Birth to weaning ADG tended (P = 0.10) to be least for heifers born
      in the first calving period; however, weaning BW decreased (P = 0.03) with
      advancing calving period. Weaning to prebreeding ADG tended (P = 0.07) to be
      least for heifers born in the first period; however, prebreeding BW was greatest
      (P < 0.01) for calves born in the first period. Heifer ADG from the beginning of
      the breeding season to pregnancy diagnosis was greater (P = 0.03) for heifers
      born in the third vs. first calving period. Heifers cycling at the beginning of
      the breeding season decreased (P < 0.01) with advancing calving date (70, 58, and
      39%, respectively) and 45 d pregnancy rates were lowest (P = 0.02) for heifers
      born in the third calving period (90, 86, and 78%, respectively). Birth date of
      the first calf of the heifer and birth BW decreased (P < 0.01) if the heifer was
      born in the first calving period. First calf progeny had the greatest (P <= 0.10)
      weaning BW if born to a heifer born in the first calving period. As steer calving
      period advanced, weaning BW decreased (P < 0.01). Calving period did not affect
      (P = 0.81) feedlot ADG. As calving period advanced, HCW, marbling score, and
      yield grade decreased (P < 0.01). The percentage of steers grading USDA small
      marbling was not affected (P = 0.13) by calving period; however, the percentage
      of steers grading USDA modest marbling or greater and the total carcass value
      declined (P <= 0.01) as calving period advanced. Heifer calves born during the
      first 21 d of the spring calving season had greater weaning, prebreeding, and
      precalving BW; greater percent cycling before breeding; and greater pregnancy
      rates compared with heifers born in the third period. First calf progeny also had
      an earlier birth date and greater weaning BW. Steer calves born during the first
      21 d of the calving season had greater weaning, final, and carcass weights;
      greater marbling scores; a greater percentage grading USDA modest or greater; and
      greater carcass value. Calving period of progeny significantly impacts
      performance.

PMID- 22871929
TI  - The accuracies of DNA-based estimates of genetic merit derived from Angus or
      multibreed beef cattle training populations.
AB  - Several organizations have developed prediction models for molecular breeding
      values (MBV) for quantitative growth and carcass traits in beef cattle using
      Bovine SNP50 genotypes and phenotypic or EBV data. Molecular breeding values for
      Angus cattle have been developed by IGENITY, Pfizer Animal Genetics, and a
      collaboration between researchers from Iowa State University and the University
      of Missouri-Columbia (ISU/UMC). The U.S. Meat Animal Research Center (USMARC;
      Clay Center, NE) has also developed MBV for 16 cattle breeds using 2 multibreed
      populations, the Germplasm Evaluation (GPE) Program and the 2,000 Bull Project
      (2K(ALL)), and 2 single breed subpopulations of the 2,000 Bull Project, Angus
      (2K(AN)) and Hereford (2K(HH)). In this study, these MBV were assessed relative
      to commercial ranch EBV estimated from the progeny phenotypes of Angus bulls
      naturally mated in multisire breeding pastures to commercial cows: 121 for USMARC
      MBV, 99 for ISU/UMC MBV, and 29 for IGENITY and Pfizer MBV (selected based on
      number of progeny carcass records). Five traits were analyzed: weaning weight
      (WW), HCW, marbling score (MS), rib-eye muscle area (RE), and, for IGENITY and
      Pfizer only, feedlot ADG. The average accuracies of MBV across traits were 0.38
      +/- 0.05 for IGENITY, 0.61 +/- 0.12 for Pfizer, 0.46 +/- 0.12 for ISU/UMC, 0.16
      +/- 0.04 for GPE, 0.26 +/- 0.05 for 2K(ALL), 0.24 +/- 0.04 for 2K(AN), and 0.02
      +/- 0.12 for 2K(HH). Angus-based MBV (IGENITY, Pfizer, ISU/UMC, and 2K(AN))
      explained larger proportions of genetic variance in this population than GPE,
      2K(ALL), or 2K(HH) MBV for the same traits. In this data set, IGENITY, Pfizer,
      and ISU/UMC MBV were predictive of realized performance of progeny, and
      incorporation of that information into national genetic evaluations would be
      expected to improve EPD accuracy, particularly for young animals.

PMID- 22871930
TI  - Relationships among performance, residual feed intake, and product quality of
      progeny from Red Angus sires divergent for maintenance energy EPD.
AB  - Energy expenditure is a physiological process that may be closely associated with
      residual feed intake (RFI). The maintenance energy (ME(M)) EPD was developed by
      the Red Angus Association of America (RAAA) and is used as an indicator of energy
      expenditure. The objectives of this study were to evaluate and quantify the
      following relationships using progeny of Red Angus (RA) sires divergent for ME(M)
      EPD: 1) postweaning RFI and finishing phase feed efficiency (FE), 2) postweaning
      RFI and end-product quality, and 3) postweaning RFI and sire ME(M) EPD. A total
      of 12 RA sires divergent for ME(M) EPD were chosen using the RAAA-generated ME(M)
      EPD values and were partitioned into 2 groups: high ME(M) EPD (>=4 Mcal/mo) and
      low ME(M) EPD (<4 Mcal/mo), based on the breed average of 4 Mcal/mo. Commercial
      crossbred cows were inseminated to produce 3 cohorts of progeny, which were
      tested for postweaning RFI (cohorts 1, 2, and 3) and finishing phase FE (cohorts
      1 and 3). Results indicate that postweaning RFI and finishing phase FE of steer
      progeny tended to be positively correlated (r = 0.38; P = 0.06) in cohort 1 and
      were positively correlated (r = 0.50; P = 0.001) in cohort 3. In addition,
      postweaning RFI was not phenotypically correlated (P > 0.05) with any carcass
      traits or end-product quality measurements. Sire ME(M) EPD was phenotypically
      correlated (P < 0.05) with carcass traits in cohort 1 (HCW, LM area, KPH, fat
      thickness, and yield grade) and cohort 2 (KPH and fat thickness). Since variation
      in measured LM area was not explained by the genetic potential of rib eye area
      EPD, and therefore, the observed correlation between sire ME(M) EPD and measured
      LM area may suggest an association between ME(M) EPD and LM area. A correlation
      (r = 0.24; P = 0.02) was observed between postweaning RFI and ultrasound
      intramuscular fat percentage in cohort 2 but was not detected in cohorts 1 or 3.
      In addition, no phenotypic relationship was observed (P > 0.05) between progeny
      postweaning RFI and sire ME(M) EPD. Therefore, results suggest 1) RFI measured
      during the postweaning growth phase is indicative of FE status in the finishing
      phase, 2) neither RFI nor sire ME(M) EPD negatively affected carcass or end
      product quality, and 3) RFI and sire ME(M) EPD are not phenotypically associated.

PMID- 22871931
TI  - Effects of supplemental molybdenum on animal performance, liver copper
      concentrations, ruminal hydrogen sulfide concentrations, and the appearance of
      sulfur and molybdenum toxicity in steers receiving fiber-based diets.
AB  - Poor performance and S-induced polioencephalomalacia (sPEM) have been observed in
      ruminant livestock in high-S drinking water regions. No gainful method of
      removing S from drinking water is available and therefore a feed supplement that
      negates the effects of high-S water is needed. Our objective was to determine if
      supplementing Mo improves health and performance of steers administered a high
      fiber diet and high-S drinking water. We hypothesized that if the supplemental Mo
      adequately bound excess S in the rumen, it would not be available at toxic
      concentrations. Yearling steers (n = 96; 260.0 +/- 1.3 kg BW) were stratified by
      pretrial BW into 12 feedlot pens (n = 8 steers per pen). One of 3 treatments, low
      S water (LS; 375 mg SO(4)/L), high-S water (HS; 2,218 mg SO(4)/L), or high-S
      water plus Mo (HSMO; 2,218 mg SO(4)/L; 187.5 mg Mo/kg DM), were randomly assigned
      to pens within 4 blocks for a 56-d trial. Body weights were recorded on d -2, -1,
      29, 56, and 57, ruminal H(2)S concentrations were measured by rumenocentesis on d
      -1, 29, and 57, and liver biopsies were performed on d -1 and 57. Performance
      data were analyzed over the 56-d trial period (overall) as well as over 2
      periods: Period 1 (d 0 to d 28) and Period 2 (d 29 to d 56). One case of sPEM was
      confirmed by the presence of cortical lesions in the HS treatment group. Daily
      DMI and ADG were affected by treatment and period (P < 0.001) main effects. The
      LS steers had the greatest (P < 0.05) DMI followed by HS and HSMO steers,
      respectively. Similar results were observed for ADG. Daily water intake was
      affected (P < 0.001) by period only, with greater daily water intake in Period 2
      than Period 1. Change in hepatic concentrations of Cu, Fe, and Mo over the course
      of the trial were all affected (P < 0.001) by treatment. Hepatic Cu increased
      from d 1 to 57 in LS and HS steers but was depleted in HSMO steers. Hepatic Fe
      and Mo increased in HSMO steers only. Ruminal H(2)S concentrations were affected
      by treatment (P < 0.021), with greater H(2)S concentrations in HSMO compared with
      LS and HS steers. Signs of Mo toxicity such as severe diarrhea, loss of body
      condition, anorexia, changes in hair color, and stiffness in joints were observed
      in the Mo supplemented steers. These results indicate that added dietary Mo does
      not adequately bind excess S in the rumen, causing aggravated toxic effects from
      potentially both the high dietary S and Mo.

PMID- 22871932
TI  - Effects of glucose and volatile fatty acids on blood ghrelin concentrations in
      calves before and after weaning.
AB  - The effects of feeding and intravenous injections of glucose and VFA on blood
      ghrelin concentrations were investigated in calves before and after weaning.
      Eight Holstein bull calves were fed whole milk, allowed free access to solid
      feeds, and weaned at 7 wk. Measurements were carried out at 2, 4, 6, 9, 11, and
      13 wk, at which time jugular blood samples were taken from 4 calves through a
      catheter from 10 min before to 120 min after their morning feed at 10 min
      intervals (Exp. 1). An additional 4 calves of the same age were intravenously
      injected with glucose (1.0 mmol.kg BW(-1)) and a solution of VFA (2.4 mmol.kg BW(
      1), acetate:propionate:butyrate in a 6:3:1 ratio) using a catheter, and jugular
      blood samples were taken temporally relative to the injection time (Exp. 2). In
      Exp. 1, blood ghrelin concentrations decreased (P < 0.05) after feeding at all
      ages. However, preprandial ghrelin concentrations were less (P = 0.025) and the
      degree of postprandial depression of ghrelin tended to be greater during the
      postweaning period (P = 0.084) than during the preweaning period. Blood glucose
      concentrations increased after feeding during the preweaning period (P < 0.05),
      whereas blood acetate concentrations increased during the postweaning period (P <
      0.05). In Exp. 2, injection of VFA induced a greater decrease in blood ghrelin
      concentrations than glucose injection throughout the entire period (P < 0.05).
      These results indicate that weaning reduces the basal concentration of blood
      ghrelin because the circulating VFA derived from ruminal fermentation may more
      strongly depress blood ghrelin concentrations than glucose.

PMID- 22871933
TI  - Effects of zilpaterol hydrochloride and days on the finishing diet on feedlot
      performance, carcass characteristics, and tenderness in beef heifers.
AB  - British * Continental heifers (n = 3,382; initial BW = 307 kg) were serially
      slaughtered to determine if increasing days on the finishing diet (DOF) mitigates
      negative consequences of zilpaterol HCl (ZH) on quality grade and tenderness of
      beef. A 2 * 3 factorial arrangement of treatments in a completely randomized
      block design (36 pens; 6 pens/treatment) was used. Zilpaterol HCl (8.33 mg/kg DM)
      was fed 0 and 20 to 22 d before slaughter plus a 3 to 5 d withdrawal to heifers
      spending 127, 148, and 167 DOF. Feedlot and carcass performance data were
      analyzed with pen as the experimental unit. Three hundred sixty carcasses (60
      carcasses/treatment) were randomly subsampled, and strip loin steaks were aged
      for 7, 14, and 21 d for assessment of Warner-Bratzler shear force (WBSF) and
      slice shear force (SSF) with carcass serving as the experimental unit for
      analysis. No relevant ZH * DOF interactions were detected (P > 0.05). Feeding ZH
      during the treatment period increased ADG by 9.5%, G:F by 12.5%, carcass ADG by
      33.6%, carcass G:F by 35.9%, carcass ADG:live ADG by 15.6%, HCW by 3.2% (345 vs.
      356 kg), dressing percent by 1.5%, and LM area by 6.5% and decreased 12th-rib fat
      by 5.2% and yield grade (YG) by 0.27 units (P < 0.01). Feeding ZH tended to
      decrease marbling score (437 vs. 442 units; P = 0.10) and increased WBSF at 7
      (4.25 vs. 3.47 kg; P < 0.01), 14 (3.57 vs. 3.05 kg; P < 0.01), and 21 d (3.50 vs.
      3.03 kg; P < 0.01). Feeding ZH decreased empty body fat percentage (EBF; 29.7%
      vs. 30.3%; P < 0.01) and increased 28% EBF adjusted final BW (473.4 vs. 449.8 kg;
      P < 0.01). Analysis of interactive means indicated that the ZH * 148 DOF group
      had a similar percentage of USDA Prime, Premium Choice, Low Choice, and YG 1, 2,
      3, 4, and 5 carcasses (P > 0.10) and decreased percentage of Select (30.4 vs.
      36.6%; P = 0.03) and Standard (0.2 vs. 0.9%; P = 0.05) carcasses compared with
      the control * 127 DOF group. As a result of ZH shifting body composition,
      extending the DOF of beef heifers is an effective feeding strategy to equalize
      carcass grade distributions. This can be accomplished along with sustaining the
      ZH mediated advantages in feedlot and carcass weight gain.

PMID- 22871934
TI  - Use of embryo transfer seven days after artificial insemination or transferring
      identical demi-embryos to increase twinning in beef cattle.
AB  - Our objectives were to determine pregnancy rate, fetal loss, and number of calves
      born in beef cattle after a fixed-time transfer of an embryo 7 d after a fixed
      time artificial insemination (TAI) of cows (Exp. 1) and after transfer of 2 demi
      embryos into a single heifer recipient (Exp. 2). In Exp. 1 after synchronization
      of ovulation, during 2 yr, 297 suckled beef cows were assigned randomly to 1 of 3
      treatments: 1) on d 2 cows received a single TAI (TAI-2; n = 99), 2) a fixed-time
      direct transfer, frozen and thawed embryo placed in the uterine horn ipsilateral
      to the ovary containing a corpus luteum (CL) on d 9 embryo transfer (ET-9; n =
      99), or 3) cows received TAI on d 2 and a frozen and thawed direct transfer
      embryo placed in the uterine horn ipsilateral to the ovary containing a CL on d 9
      (TWIN) treatments (n = 99). Fetal number and viability were determined with
      ultrasonography at 33 to 35 d and 90 to 100 d after insemination. In Exp. 2, 74
      crossbred recipient heifers were assigned randomly to receive either 1) a single
      whole fresh embryo (WHOLE; n = 37) or 2) 2 identical fresh demi-embryos (SPLIT; n
      = 37) in the uterine horn ipsilateral to the CL 7 d after an observed estrus.
      Ultrasonography was used on d 33, 69, and 108 to determine presence and number of
      embryos or fetuses. Palpation per rectum was used to determine pregnancy status
      on d 180 of gestation and number of live calves was recorded at birth. In Exp. 1
      pregnancy rates on d 30 to 35 were greater (P < 0.05) for TWIN- (48.5%) and TAI-2
      (47.5%) than for ET-9- (33.3%) treated cows. Of the 48 pregnant cows in the TWIN
      treatment, 21 were twin pregnancies whereas there was 1 twin pregnancy in the TAI
      2 treatment. As a result, TWIN cows had more fetuses (P < 0.05) as a proportion
      of all treated cows (69.7%) than TAI-2- (48.5%) or ET-9-(33.3%) treated cows, and
      cows in the TWIN treatment gave birth to more (P < 0.01) calves (n = 55) compared
      with cows in the ET treatment (n = 23) whereas cows in the TAI-2 treatment (n =
      40) were intermediate. In Exp. 2 heifers receiving SPLIT (81.1%) had greater (P <
      0.05) pregnancy rates on d 33 than heifers receiving WHOLE (40.5%). Of the SPLIT
      heifers that were confirmed pregnant at d 33 after transfer, 57% were gestating
      twin fetuses. Embryonic or fetal loss from d 33 to birth was greater (P < 0.01)
      in heifers in the SPLIT treatment (40.0%) compared with the WHOLE treatment
      (0.0%), but number of calves per female treated was greater (P < 0.05) in heifers
      in the SPLIT treatment (75.0%) compared with heifers in the WHOLE treatment
      (40.5%). We conclude that transferring an embryo into a cow 7 d after TAI did not
      increase the pregnancy rate in Exp.1. However, transferring 2 demi-embryos into a
      single heifer recipient increased pregnancy rate at 33 d of gestation whereas
      both methods of inducing twinning resulted in a greater number of calves per
      female treated. In addition, embryonic or fetal loss associated with unilateral
      twin pregnancies in heifers occurred at rates greater than those associated with
      single-fetus pregnancies.

PMID- 22871935
TI  - Net energy of diets containing wheat-corn distillers dried grains with solubles
      as determined by indirect calorimetry, comparative slaughter, and chemical
      composition methods.
AB  - The NE content of diets containing wheat-corn distillers dried grains with
      solubles (wcDDGS; 1:1 ratio) fed to growing pigs was determined using the
      comparative slaughter (CS), indirect calorimetry (IC), and chemical composition
      (CH) methods. The experimental diets were a corn-soybean meal control diet
      (CTRL), CTRL + 15% wcDDGS, and CTRL + 30% wcDDGS. In Exp. 1, 56 barrows (18.5 kg
      BW) were used to determine the NE value of diets using the CS method. Pigs were
      initially placed in 8 groups (7/group), based on BW and 1 pig/group was killed at
      the start of the experiment to obtain baseline body composition. The remaining 48
      pigs were housed in pairs and allotted to the 3 diets (n = 8). Pigs had free
      access to feed and water for a 28-d period, after which 1 pig/pen was slaughtered
      to determine final body composition. Based on the CS method, NE values of 2,430,
      2,427, and 2,429 kcal/kg DM were obtained for diets containing 0%, 15%, and 30%
      wcDDGS, respectively. In Exp. 2, 18 barrows (20.4 kg BW) were used to determine
      the NE value of diets using the IC and CH methods. Pigs were individually housed
      in metabolism crates and fed the 3 diets (n = 6) at 550 kcal ME/kg BW/d for a 16
      d period. Feces and urine were collected from d 11 to 16, followed by measurement
      of O(2) consumption, CO(2) production, and urinary N, over a 36-h period using an
      IC system. For the IC method, NE values of 2,586, 2,513, and 2,520 kcal/kg DM
      were obtained for diets containing 0%, 15%, and 30% wcDDGS, respectively, and
      corresponding values for the CH method were 2,447, 2,451, and 2,368 kcal/kg DM,
      respectively. The NE values that were obtained with the CS, IC, and CH methods
      were not different.

PMID- 22871936
TI  - Metabolic changes and tissue responses to selection on residual feed intake in
      growing pigs.
AB  - Previous selection experiments using residual feed intake (RFI) to select pigs
      with a high feed efficiency have reported that a low RFI was associated with a
      reduced body fat content and a greater muscle glycogen content. In the current
      study, growing Large White female piglets from 2 lines divergently selected for
      RFI were used to determine the changes in energy and protein metabolisms in key
      tissues and their cross talks in response to selection. Pigs of low RFI (RFI(-);
      n = 26) or high RFI (RFI(+); n = 36) selection lines were offered free access to
      feed during postweaning and growing periods. Pigs of each line were then
      slaughtered at 19 kg (n = 8 per line) or 115 kg BW (n = 14 to 18 per line). A
      third group of pigs of the RFI(+) line was offered feed at the same level per
      metabolic BW (BW0.60) as RFI- pigs (group RFI+R, n = 14). Regardless of the
      growth period considered, G:F was less in RFI(+) pigs than in RFI(-) pigs. At 19
      kg BW, RFI(+) and RFI(-) pigs had a similar body composition and tissue lipid
      content. The fractional rate of protein synthesis and proteasome activity were
      decreased (P < 0.090) in the livers of RFI(+) pigs compared with RFI(-) pigs
      whereas activities of energy catabolic enzymes did not differ in the liver and LM
      samples. Plasma insulin was conversely greater (P = 0.049) in RFI(+) pigs at this
      stage. At 115 kg BW, enzyme activities of protein catabolism in the liver and in
      the LM did not differ (P > 0.10) between RFI(+) pigs and RFI(-) pigs. Both
      lactate dehydrogenase activity participating in glucose metabolism and
      hydroxylacylCoA dehydrogenase activity involved in fatty acid oxidation were
      greater (P < 0.05) in the liver and LM of RFI(+) pigs compared with RFI(-) pigs.
      In the liver, contrary to the LM, those differences in enzyme activities were
      directly associated with selection on RFI regardless of ADFI. Increased backfat
      depth and content and greater lipid content and adipocyte hypertrophy (P < 0.05)
      in subcutaneous adipose tissue were reported in RFI(+) pigs compared with RFI(-)
      pigs at 115 kg BW without marked changes in key lipogenic enzyme activities;
      these changes were directly associated with ADFI. In conclusion, the present
      study shows an increase of catabolic pathway activities in the liver and muscle
      of RFI(+) pigs at market weight that is likely to generate more ATP compared with
      RFI(-) pigs.

PMID- 22871937
TI  - A high-protein diet induces dissociation between plasma concentrations of growth
      hormone and ghrelin in wethers.
AB  - High-carbohydrate or high-fat diets have been demonstrated to change ghrelin
      concentrations in plasma; however, there remains a need to clarify the effects of
      dietary protein on the interaction between circulating GH and ghrelin
      concentrations in the ruminant. In this study, we investigated the postprandial
      changes in plasma concentrations of GH and ghrelin and their interactions when
      wethers were fed either a high-protein (HP; 40% CP) or a low-protein (LP; 10% CP)
      diet for 2 wk. The wethers were divided into 2 groups and fed once a day for 2 wk
      in a randomized crossover design. Each diet contained the same level of ME. Blood
      was collected from the animals at specific times over 24 h to measure hormones
      and metabolites. Feeding once a day caused a prompt reduction in the GH and
      ghrelin concentrations regardless of the type of diet that the wethers consumed.
      The preprandial concentrations (P = 0.04), area under the curve (AUC; P = 0.04),
      and incremental AUC (iAUC; P = 0.06) for ghrelin in HP-fed wethers were or tended
      to be greater than those in LP-fed wethers although concentrations for GH were
      the same for both diets (P = 0.23). In addition, the time it took for the
      postprandial ghrelin concentrations to recover to the preprandial concentrations
      was greater in HP-fed wethers than in LP-fed wethers although this was not true
      for GH concentrations. Similarly, as for ghrelin, postprandial increase (P <
      0.001) and AUC (P = 0.03) for insulin concentration was greater in the HP-fed
      wethers than in the LP-fed wethers. From these findings, we concluded that
      dietary proteins (or some other derived metabolites) may dissociate the
      interaction between plasma concentrations of GH and ghrelin in wethers.

PMID- 22871938
TI  - Prenatal administration of dexamethasone during early pregnancy negatively
      affects placental development and function in mice.
AB  - Prenatal treatment of dexamethasone, a synthetic stress hormone, leads to low
      birth weight and affects adult pathophysiology. Because fetal growth and survival
      are critically dependent on successful placental development, we aimed to
      investigate the effects of prenatal dexamethasone exposure on placental growth
      and function, particularly focusing on issues surrounding the time of stress
      exposure in a developmental context. Dexamethasone was administered at a dosage
      of 1 mg/kg BW (DEX1) or 10 mg/kg BW (DEX10) intraperitoneally at gestational d
      7.5, 8.5, and 9.5 in pregnant mice. Placentas were then dissected at gestational
      d 11.5 and 18.5. Placental size and weight were reduced at d 11.5 in a dose
      dependent manner (P = 0.11 for saline vs. DEX1 and P < 0.001 for DEX1 vs. DEX10
      in size; P = 0.34 for saline vs. DEX1 and P < 0.01 for DEX1 vs. DEX10 in weight).
      In contrast, a considerable heterogeneity was shown at d 18.5, especially in
      DEX10-treated mice. Some placentas were small and malformed whereas some were
      enlarged with structural abnormalities in spongiotrophoblasts and labyrinth
      layers. Although placental overgrowth under such condition seemed to compromise
      fetal demand for nutrient supply, disorganized cell structure with reduced fetal
      vasculature observed in large placentas suggests that prenatal stress exposure
      during the early gestational period negatively affects placental development and
      efficiency.

PMID- 22871939
TI  - Effects of shade on welfare and meat quality of grazing sheep under high ambient
      temperature.
AB  - This study was conducted to evaluate the effects of providing shade on growth
      performance, welfare, and meat quality of grazing sheep under high ambient
      temperature. A total of 120 healthy male Ujumqin wool sheep (a local breed; BW =
      18.7 +/- 1.27 kg; 14 wk old) were randomly and equally divided into shaded and
      unshaded treatments with 3 pens per treatment. Sheep were grazed on an unshaded
      pastureland from 0600 to 1000 h and 1400 to 1800 h. During other times, sheep
      were confined in shaded or unshaded pens. Body weight was recorded on d 1 and 42
      of the experiment. Rectal temperature and respiration rate were recorded on d 7,
      14, 21, 28, 35, and 42. At end of the trial, sheep were blood sampled and
      slaughtered to collect meat samples. Respiration rate was greater (P < 0.05) in
      the unshaded sheep than shaded sheep on d 14, 21, 28, 35, and 42 of the trial
      whereas no significant differences were found on d 7. Moreover, no differences
      were observed in final BW, ADG, or rectal temperature throughout the trial. The
      pH at 24 h postmortem (pH(24)) and cooking loss were greater (P < 0.01) in
      unshaded than shaded sheep. On the contrary, lightness (L*), redness (a*) and
      yellowness (b*) values at 24 h postmortem were lower (P < 0.05) in unshaded
      versus shaded sheep. The sheep in the unshaded group had a greater (P < 0.05)
      cortisol concentration compared with the shaded group. Sheep in the shaded group
      had lower creatine kinase activity (P < 0.01) as well as observed for glucose (P
      < 0.05), triiodothyronine (P < 0.01), and thyroxine (P < 0.05) concentrations and
      white blood cell count (P < 0.05). Compared with the unshaded group, sheep in the
      shaded group had a greater lymphocytes (LYM) count (P < 0.05). In contrast, the
      opposite was true for neutrophils (NEU) count (P < 0.01) and NEU:LYM ratio (P <
      0.01). In conclusion, the shade cloth, although not enhancing ADG, improved meat
      quality traits and certain stress parameters in grazing sheep reared under high
      ambient temperature.

PMID- 22871940
TI  - Space allowance for gestating sows in pens: behavior and immunity.
AB  - Different floor space allowances for dry, pregnant sows in pens were evaluated to
      determine the impacts of space on sow behavior, immune, and cortisol measures.
      The experiment consisted of 6 replications (blocks 1 to 6; n = 20 sows/group),
      and within each replicate, physiological measurements were recorded for 2
      consecutive pregnancies. A total of 152 sows were measured at 1 gestation, and 65
      of those sows were measured at the successive gestation (n = 217). Groups of 5
      sows/pen were assigned to 1.4, 2.3, or 3.3 m(2) of floor space/sow or of 5 sows
      in individual stalls (1.34 m(2)). Behavior measures were stand, sit, lie, walk,
      drink, oral-nasal-facial (ONF), sham chew, and aggression. Immune traits included
      both descriptive and functional aspects and cortisol. At d 90 +/- 5 of gestation,
      the occurrence of ONF behaviors increased from 0300 to 1500 h, and lying behavior
      decreased from 0700 to 1100 h for sows kept at 2.3 m(2). Sows in stalls displayed
      more (P < 0.05) ONF from 1500 to 2300 h. Stand, sit, drink, ONF, and sham-chew
      behaviors were affected by floor space; sows in pens at 2.3 m(2) performed more
      ONF, and sows at 1.4 m(2) performed more sham chewing (P < 0.05). Standing (P =
      0.05) and drinking (P = 0.06) were increased, but lying (P = 0.06) was reduced
      for sows in pens at 2.3 or 3.3 m(2). Sitting and drinking were greater but lying
      was less for sows in stalls compared with sows in pens (P < 0.01). Immune traits
      were affected by treatment (P < 0.05); neutrophils were less and lymphocytes were
      greater, resulting in a reduced neutrophil:lymphocyte (N:L) ratio (P < 0.05) for
      sows in pens at 3.3 m(2). Natural killer cell was greater but lymphocyte
      proliferation was less for sows in pens at 1.4 m(2) (P < 0.05). Sows in stalls
      had greater N:L ratio than sows in pens (P < 0.05). For sows in pens, linear and
      quadratic responses were detected for behavior and immune traits. As floor space
      increased, walking and aggression increased. As floor space decreased,
      neutrophils, N:L, and natural killer cell increased, but as floor space increased
      lymphocyte proliferation increased. On the basis of behavioral and physiological
      responses shown by sows in all 4 environments it is apparent that neither floor
      space nor stall environment provided adequate or quality of space to improve sow
      well-being. However, the differential behavioral and physiological mechanisms
      initiated by sows in response to their specific environment the sows were able to
      evoke the appropriate response(s) needed to adequately adapt to their
      environment.

PMID- 22871941
TI  - Effects of nordihydroguaiaretic acid on in vitro fermentation profiles of rumen
      bacteria.
AB  - Nordihydroguaiaretic acid (NDGA) is a secondary plant metabolite with
      antimicrobial properties, and therefore may have potential as a rumen modifier.
      Two in vitro experiments were conducted to determine the usefulness of NDGA as a
      rumen modifier. Exp. 1 evaluated the effect of adding 0, 5, 10, 50, and 100 mg/mL
      NDGA on growth of pure and mixed cultures of rumen bacteria. Growth of all
      cultures except Butyrivibrio fibrisolvens H17c was inhibited at 50 mg/mL NDGA (P
      < 0.05). Cultures from whole rumen fluid and B. fibrisolvens H17c were inhibited
      with 100 mg/mL NDGA (P < 0.05). Exp. 2 evaluated additions of NDGA on IVDMD (48
      h) and VFA production. Three dietary substrates simulating different resources
      available for livestock production and 5 concentrations of NDGA were compared
      with monensin (47.5 MUg/mL, MON, Elanco Animal Health, Indianapolis, IN).
      Substrates included (DM basis) 100% meadow hay (H100), 50% alfalfa with 50%
      ground corn (H50), and 90% ground corn with 10% alfalfa (H10). Treatments were 0
      (Control; CON), 20, 40, 60, 80 MUg/mL NDGA and MON. Treatment means were compared
      using 2 single degree of freedom contrasts (0 MUg/mL NDGA vs. MON and NDGA vs.
      MON) and orthogonal polynomial contrasts within NDGA concentrations. Monensin
      fermented with H100 had the least (P < 0.01) IVDMD. A linear increase in IVDMD
      was observed for H50 (P < 0.01) but not H10 or 100 (P > 0.40). Acetate was
      quadratic for all substrates tested with NDGA (P < 0.01) and adding NDGA vs. MON
      resulted in 9% greater values (P < 0.01). Propionate increased by addition of MON
      compared with CON, which was opposite for acetate. Propionate showed the greatest
      increase with addition of MON and was dependent on diet vs. CON (H100 vs.H50 vs.
      H10; 22.5%, 44.4%, and 30.2%, respectively). When H100 was used, total VFA
      declined linearly by 61% with increasing NDGA (P < 0.01), whereas H50 and H10
      were quadratic (P < 0.01) with the greatest total VFA resulting from 40 and 80
      mg/mL NDGA for H50 and H10, respectively. Addition of NDGA tended to decrease
      total VFA (P =0.06) for H100 and H10 by 18.5% and 9.0%, respectively; however,
      H50 did not differ (P = 0.82) compared with MON. Butyrate increased linearly with
      increasing NDGA for H10 (P < 0.03) and quadratic for H50 and H100 (P < 0.01). The
      lowest overall acetate:propionate ratio was obtained with addition of MON to H10
      (1.35) and the greatest ratio resulted from adding 60 MUg/mL NDGA to H100 (3.63).
      Rumen fermentation was responsive to NDGA, and the response is dependent on diet.

PMID- 22871943
TI  - Severe hyperkalemia in critically ill patients treated with prophylactic doses of
      enoxaparin.

PMID- 22871944
TI  - The prognostic value of cardiopulmonary exercise testing in vascular surgery
      patients.

PMID- 22871945
TI  - Commentary on 'Early results from the ENGAGE Registry: real world performance of
      the Endurant Stent Graft for endovascular AAA repair in 1262 patients'.

PMID- 22871946
TI  - Tailor-made synthesis of various backbone-substituted imidazolinium salts by
      triflic anhydride mediated intramolecular cyclisation.
AB  - We have found a Tf(2)O-mediated intramolecular cyclization reaction and have
      revealed an intriguing stereoselectivity and a regioselectivity during the
      preparation of intermediate alcohols, which allow for the tailor-made synthesis
      of various backbone-substituted imidazolinium salts, and structurally specific
      syn-4,5-disubstituted imidazolinium salts.

PMID- 22871947
TI  - Catching transcriptional regulation by thermostatistical modeling.
AB  - Gene expression is frequently regulated by multiple transcription factors (TFs).
      Thermostatistical methods allow for a quantitative description of interactions
      between TFs, RNA polymerase and DNA, and their impact on the transcription rates.
      We illustrate three different scales of the thermostatistical approach: the
      microscale of TF molecules, the mesoscale of promoter energy levels and the
      macroscale of transcriptionally active and inactive cells in a cell population.
      We demonstrate versatility of combinatorial transcriptional activation by
      exemplifying logic functions, such as AND and OR gates. We discuss a metric for
      cell-to-cell transcriptional activation variability known as Fermi entropy.
      Suitability of thermostatistical modeling is illustrated by describing the
      experimental data on transcriptional induction of NFkappaB and the c-Fos protein.

PMID- 22871948
TI  - Previous abortion is a positive predictor for ongoing pregnancy in the next cycle
      in women with repeated IVF failures.
AB  - Early pregnancy loss is common among women treated with assisted reproduction
      treatment, but whether it is a prognostic factor for success in subsequent IVF
      cycles is not well established. The aim of this study was to determine whether a
      biochemical pregnancy (BP) or spontaneous abortion (SA) affects the pregnancy
      rates in the following cycle. A retrospective study of 2687 women undergoing 6678
      cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate
      (PR) per cycle was compared between patients with a pregnancy loss versus a
      negative beta-HCG in their previous cycles. Multivariate analysis of factors
      affecting ongoing pregnancy rate was performed. BP and/or SA in the first three
      cycles did not significantly alter the chances to conceive (16.9% patients with
      BP and/or SA in the previous cycle versus 16.5% patients with no previous
      pregnancy). From cycle 4 onwards, the presence of a previous abortion (either BP
      or SA) was associated with better ongoing PR (23.0% versus 11.2%, P<0.001). In
      conclusion, BP and/or SA in a previous cycle appears to be a positive marker for
      success in subsequent cycles in patients with repeated IVF failures. These
      results should be further investigated in this challenging group of patients.

PMID- 22871949
TI  - Monozygotic multiple pregnancies following IVF: a case report series of rare
      experience.
AB  - Monozygotic multiple pregnancies are three times more common after assisted
      reproduction (with or without IVF) than after spontaneous conception (1.2% versus
      0.4%). These pregnancies are associated with multiple maternal and fetal risks.
      This article is a description of nine cases of monozygotic pregnancies following
      IVF at the OVO Clinic (Montreal) between January 2007 and August 2011 and a
      scientific review of the literature on monozygotic multiple pregnancies after
      assisted reproductive treatment found in the MEDLINE and Cochrane Databases. In
      this retrospective series, 3522 embryos were transferred and 1033 pregnancies
      were obtained, of which there were nine monozygotics (0.87%). The exact mechanism
      behind this increased frequency remains uncertain. Possible explanations
      associated with fertility treatments include alterations of the zona pellucida,
      transfers at the blastocyst stage, prolonged culture, preimplantation genetic
      diagnosis, ovarian stimulation and maternal age. Assisted reproduction treatment
      appears to increase monozygotic pregnancies; however, the rate is still low and
      therefore it is difficult to exactly conclude the real mechanism. There are two
      types of multiple pregnancy: the dizygotic (two different embryos) and the
      monozygotic (one embryo which splits to make two identical genetic embryos). We
      know the risk factors for dizygotic pregnancies, but the mechanism of monozygotic
      pregnancies remains unclear. Assisted reproduction treatment seems to increase
      the multiple monozygotic pregnancy rate to 3-times more than that in nature.
      Several possibilities could be suspected as responsible for these monozygotic
      multiple pregnancies - advanced maternal age, alterations of the zona pellucida,
      transfers at the blastocyst stage, prolonged culture and ovarian stimulation -
      but a absolute explanation is not yet defined. This article is a scientific
      review of the literature on monozygotic multiple pregnancies after IVF treatment
      and a description of nine cases following IVF treatment at the OVO Clinic in
      Montreal between January 2007 and August 2011. The bibliographic references were
      found in the Medline and Cochrane Database.

PMID- 22871951
TI  - New weighting methods for phylogenetic tree reconstruction using multiple loci.
AB  - Efficient determination of evolutionary distances is important for the correct
      reconstruction of phylogenetic trees. The performance of the pooled distance
      required for reconstructing a phylogenetic tree can be improved by applying large
      weights to appropriate distances for reconstructing phylogenetic trees and small
      weights to inappropriate distances. We developed two weighting methods, the
      modified Tajima-Takezaki method and the modified least-squares method, for
      reconstructing phylogenetic trees from multiple loci. By computer simulations, we
      found that both of the new methods were more efficient in reconstructing correct
      topologies than the no-weight method. Hence, we reconstructed hominoid
      phylogenetic trees from mitochondrial DNA using our new methods, and found that
      the levels of bootstrap support were significantly increased by the modified
      Tajima-Takezaki and by the modified least-squares method.

PMID- 22871952
TI  - Real-time multimodal axillary vein imaging enhances the safety and efficacy of
      axillary vein catheterization in neurosurgical intensive care patients.
AB  - BACKGROUND: Controversy exists regarding the increased safety profile when
      ultrasound is used for central venous catheters inserted in the subclavian or
      axillary vein. The critically ill neurosurgical patient presents unique
      considerations for the optimal central line approach. METHODS: This report is a
      retrospective chart review of 6 neurosurgical intensive care patients in whom an
      ultrasound-guided, transpectoral, axillary vein catheterization was attempted. A
      sterile technique was observed. The anatomy was confirmed using combined
      transverse, longitudinal, and Doppler flow images. The needle tip was advanced
      into the axillary vein under real-time ultrasound using an in-plane technique.
      The central venous catheter was inserted using the Seldinger technique. A chest
      radiograph was obtained after each line. RESULTS: Five of the 6 central lines
      were inserted easily, without complications. The sixth central line was inserted
      without complications but more proximally because of difficulty in visualizing
      the axillary vein on account of the patient's morbid obesity and severe
      hypovolemia. CONCLUSIONS: This series illustrates new and useful aspects of
      ultrasound use in transpectoral axillary vein catheterization: it requires
      minimal additional training; it combines the real time, in-plane technique with
      transverse, longitudinal, and Doppler color flow images; and it is used safely in
      the critically ill neurosurgical patient. The data on infraclavicular central
      venous catheters indicate decreased line sepsis, arterial punctures, and venous
      thrombosis while improving nursing care and patient comfort. This technique's
      potential for decreasing the risk of pneumothorax may make it a reasonable option
      for many critically ill patients in whom other central venous catheter approaches
      may not be ideal.

PMID- 22871953
TI  - Sevoflurane and isoflurane preconditioning provides neuroprotection by inhibition
      of apoptosis-related mRNA expression in a rat model of focal cerebral ischemia.
AB  - BACKGROUND: This study aimed to examine the effects of sevoflurane or isoflurane
      preconditioning on cerebral ischemia/reperfusion-induced inflammation, oxidative
      stress, and lipid peroxidation and test the hypothesis that the underlining
      mechanism of the protective effect of preconditioning involves changes in the
      apoptotic gene expression profiles in an experimental model of middle cerebral
      artery occlusion in rats. METHODS: Twenty-four adult male rats were randomly
      divided into 3 groups: control (n=8), sevoflurane (n=8), and isoflurane (n=8).
      For preconditioning, these 3 groups were exposed to 40% O2, 2% sevoflurane, and
      1.5% isoflurane, respectively, for 60 minutes, followed immediately by 1 hour of
      middle cerebral artery occlusion and then 6 hours of reperfusion. Blood and brain
      tissue samples were collected for determination of blood gas tension, tumor
      necrosis factor-alpha, interleukin-6, and interleukin-1beta. Brain tissue samples
      were collected for determination of the wet/dry ratio, myeloperoxidase,
      malondialdehyde, and total RNA and also for histologic examinations. RESULTS:
      Tumor necrosis factor-alpha, interleukin-1beta, and myeloperoxidase levels
      decreased and antioxidant enzyme levels increased in the sevoflurane group
      compared with the control and isoflurane groups. Proapoptotic genes (Tnf,
      Tnfrsf10b, and Tp53) downregulated and antiapoptotic genes (Aven, Bcl2, Bcl2l2,
      and Prok2) upregulated with sevoflurane treatment compared with the isoflurane
      and control groups. Both isoflurane and sevoflurane pretreatment decreased
      malondialdehyde, Dffb, the wet/dry ratio, and injury score and upregulated Bax
      and Apaf 1 compared with the control group. CONCLUSIONS: Sevoflurane and
      isoflurane preconditioning ameliorates inflammation, cerebral lipid peroxidation,
      and histologic injury. Downregulation of proapoptotic molecules and upregulation
      of antiapoptotic molecules may be associated with this effect.

PMID- 22871954
TI  - Updates on B-cell immunotherapies for systemic lupus erythematosus and Sjogren's
      syndrome.
AB  - PURPOSE OF REVIEW: Last year was marked by important clinical and mechanistic
      studies that improved our understanding of B-cell immunotherapy for systemic
      lupus erythematosus (SLE) and Sjogren's syndrome. Here, we will highlight the
      most relevant studies published in the last 18 months. RECENT FINDINGS: The
      highlight of the year was the approval of belimumab on the basis of two major
      trials. On the flip side, the disappointing results of rituximab in lupus
      nephritis provided a clinical and mechanistic counterpoint in SLE. Still, major
      limitations in the LUpus Nephritis Assessment with Rituximab (LUNAR) trial,
      positive subset analysis and new open studies and registries continue to provide
      hope for and major insights into the use of B-cell depletion. In Sjogren's
      syndrome, the role of B-cell depletion has been further investigated, both for
      glandular and extraglandular manifestations of the disease with mixed results in
      a disease in which outcomes are notoriously hard to measure. SUMMARY: The
      approval of anti-B cell activating factor therapy and an increasing body of open
      studies with rituximab as well as subset studies and secondary analysis of the
      Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus
      Erythematosus (EXPLORER) and LUNAR trials provide hope for B-cell immunotherapy
      and significant insight into its mechanisms of action and utilization in a
      selected subset of patients. Ongoing clinical trials of other B-cell targeting
      agents are eagerly anticipated.

PMID- 22871955
TI  - Current world literature.

PMID- 22871958
TI  - Evaluation of autoimmune safety signal in observational vaccine safety studies.
AB  - Autoimmune safety evaluation is an important component of post-licensure vaccine
      safety evaluation. Recently, we published the findings from a large observational
      safety study of the quadrivalent human papillomavirus vaccine in females. From
      this study, based on two large managed care organizations, we have obtained some
      empirical data that may prove useful for the design of future vaccine safety
      studies within a managed care environment. For autoimmune conditions, a major
      challenge in vaccine safety study is to determine true incident cases in relation
      to the timing of vaccination. We found expert case review of medical records an
      indispensable component for autoimmune safety studies based on electronic health
      records. Case identification should also be expanded to include the use of
      laboratory test results or other relevant measures in addition to the disease
      specific ICD-9 diagnosis codes, when applicable. Furthermore, we recommend the
      parallel use of both safety signal evaluation that involves pattern evaluation
      for conditions that are more common, and statistical comparisons for conditions
      that are rather rare. Finally, we recommend an accompanying vaccine uptake study
      to understand the potential selection bias and confounding in a given study
      population that should be addressed with data collection and analytical
      techniques.

PMID- 22871957
TI  - Androgen receptor antagonism by divalent ethisterone conjugates in castrate
      resistant prostate cancer cells.
AB  - Sustained treatment of prostate cancer with androgen receptor (AR) antagonists
      can evoke drug resistance, leading to castrate-resistant disease. Elevated
      activity of the AR is often associated with this highly aggressive disease state.
      Therefore, new therapeutic regimens that target and modulate AR activity could
      prove beneficial. We previously introduced a versatile chemical platform to
      generate competitive and non-competitive multivalent peptoid oligomer conjugates
      that modulate AR activity. In particular, we identified a linear and a cyclic
      divalent ethisterone conjugate that exhibit potent anti-proliferative properties
      in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we
      characterize the mechanism of action of these compounds utilizing confocal
      microscopy, time-resolved fluorescence resonance energy transfer, chromatin
      immunoprecipitation, flow cytometry, and microarray analysis. The linear
      conjugate competitively blocks AR action by inhibiting DNA binding. In addition,
      the linear conjugate does not promote AR nuclear localization or co-activator
      binding. In contrast, the cyclic conjugate promotes AR nuclear localization and
      induces cell-cycle arrest, despite its inability to compete against endogenous
      ligand for binding to AR in vitro. Genome-wide expression analysis reveals that
      gene transcripts are differentially affected by treatment with the linear or
      cyclic conjugate. Although the divalent ethisterone conjugates share extensive
      chemical similarities, we illustrate that they can antagonize the AR via distinct
      mechanisms of action, establishing new therapeutic strategies for potential
      applications in AR pharmacology.

PMID- 22871959
TI  - Lab-chip HPLC with integrated droplet-based microfluidics for separation and high
      frequency compartmentalisation.
AB  - We demonstrate the integration of a droplet-based microfluidic device with high
      performance liquid chromatography (HPLC) in a monolithic format. Sequential
      operations of separation, compartmentalisation and concentration counter were
      conducted on a monolithic chip. This describes the use of droplet-based
      microfluidics for the preservation of chromatographic separations, and its
      potential application as a high frequency fraction collector.

PMID- 22871960
TI  - [Hematopoietic neoplasms discovered by chance: importance of routine blood
      analysis].

PMID- 22871961
TI  - [Acute quadriparesis as a form of presentation of a severe hyperkalemia].

PMID- 22871962
TI  - Potential contribution of femoroacetabular impingement to recurrent traumatic hip
      dislocation.
AB  - A 16-year-old boy sustained a traumatic posterior dislocation of the right hip.
      After initial closed reduction, the hip spontaneously redislocated within 2 days.
      Four days after the initial dislocation, the patient was transferred to the
      authors' institution, where a radiographic workup showed a severe capsular and
      labral disruption from the posterior aspect of the acetabulum. Subsequently, the
      patient underwent operative treatment using the technique of surgical hip
      dislocation through a digastric osteotomy as described by Ganz. Using this
      approach, the avulsed capsulolabral complex as well as the pathological head-neck
      junction, which is suspected to be a lever for the femoral head, could be fully
      addressed. The authors recommend further radiographic studies to evaluate the
      underlying pathology in traumatic dislocation of the hip as well as the described
      surgical approach, which leads to successful treatment of the entire pathology.

PMID- 22871963
TI  - Synthesis of an in vivo MRI-detectable apoptosis probe.
AB  - Cellular apoptosis is a prominent feature of many diseases, and this programmed
      cell death typically occurs before clinical manifestations of disease are
      evident. A means to detect apoptosis in its earliest, reversible stages would
      afford a pre-clinical 'window' during which preventive or therapeutic measures
      could be taken to protect the heart from permanent damage. We present herein a
      simple and robust method to conjugate human Annexin V (ANX), which avidly binds
      to cells in the earliest, reversible stages of apoptosis, to superparamagnetic
      iron oxide (SPIO) nanoparticles, which serve as an MRI-detectable contrast agent.
      The conjugation method begins with an oxidation of the SPIO nanoparticles, which
      oxidizes carboxyl groups on the polysaccharide shell of SPIO. Purified ANX
      protein is then added in the setting of a sodium borate solution to facilitate
      covalent interaction of ANX with SPIO in a reducing buffer. A final reduction
      step with sodium borohydride is performed to complete the reduction, and then the
      reaction is quenched. Unconjugated ANX is removed from the mix by microcentrifuge
      filtration. The size and purity of the ANX-SPIO product is verified by dynamic
      light scattering (DLS). This method does not require addition to, or modification
      of, the polysaccharide SPIO shell, as opposed to cross-linked iron oxide particle
      conjugation methods or biotin-labeled nanoparticles. As a result, this method
      represents a simple, robust approach that may be extended to conjugation of other
      proteins of interest.

PMID- 22871964
TI  - Blockage of nerve growth factor modulates T cell responses and inhibits allergic
      inflammation in a mouse model of asthma.
AB  - OBJECTIVE: Blockage of nerve growth factor (NGF) by anti-NGF antibodies can
      inhibit allergic airway hyper-responsiveness in mice. This study was aimed at
      determining the mechanisms underlying the action of anti-NGF in vivo. METHODS:
      BALB/c mice were sensitized with ovalbumin (OVA) and treated with anti-NGF. At 1
      day after the last challenge, their airway responsiveness and inflammation were
      examined and the levels of cytokine and transcription factor mRNA transcripts in
      the lungs and cytokines in the bronchoalveolar lavage fluid were determined. The
      frequency of different functional T cells and the levels of serum OVA-specific
      antibodies were measured. RESULTS: OVA challenge induced severe airway
      resistance, inflammation, higher levels of IL-4, TNFalpha, IL-17A, TGFbeta, GATA
      3 and RORgammaT expression and increased Th2 and Th17 cells and IgE responses,
      but decreased IFNgamma and IL-10 responses, T-bet and Foxp3 expression and Th1
      and Tregs. Treatment with anti-NGF significantly reduced allergic airway
      resistance and inflammation, up-regulated IFNgamma, IL-10, TGFbeta, T-bet, and
      Foxp3 expression, increased Th1 and Tregs, but down-regulated IL-4, TNFalpha, IL
      17A, RORgammaT and GATA-3 expression and reduced Th2 and Th17 cells, accompanied
      by increased serum IgG2a. CONCLUSIONS: Anti-NGF inhibits allergic airway
      inflammation by modulating the balance of pro- and anti-asthmatic T cell
      responses in the lungs of mice.

PMID- 22871966
TI  - Melanocortin 5 receptor signaling and internalization: role of MAPK/ERK pathway
      and beta-arrestins 1/2.
AB  - The Melanocortin 5 receptor (MC5R) is a G-protein coupled receptor (GPCR) that
      exhibits high affinity for alpha-MSH. Here we present evidence for MC5R-GFP
      internalization and subsequent recycling to cell surface, in alpha-MSH-stimulated
      HeLa cells. This melanocortin induces a biphasic activation of ERK1/2 with an
      early peak at 15min, a G(i)-protein driven, beta-arrestins 1/2 independent
      process, and a late sustained activation that is regulated by beta-arrestins 1/2.
      ERK1/2 lead to downstream phosphorylation of 90-kDa ribosomal S6 kinases (p90RSK)
      and mitogen- and stress-activated protein kinase 1 (MSK1). Only a small fraction
      (10%) of phosphorylated p90RSK and ERK1/2 translocates to the nucleus inducing c
      Fos expression. alpha-MSH also activates CREB through cAMP/PKA pathway. In 3T3-L1
      adipocytes, where MC5R is endogenously expressed, alpha-MSH also induces
      phosphorylation and cytosolic retention of the same signaling molecules. These
      findings provide new evidence on the signaling mechanisms underlying MC5R
      biological response to alpha-MSH.

PMID- 22871965
TI  - Phorbol esters enhance 1alpha,25-dihydroxyvitamin D3-regulated 25-hydroxyvitamin
      D-24-hydroxylase (CYP24A1) gene expression through ERK-mediated phosphorylation
      of specific protein 3 (Sp3) in Caco-2 cells.
AB  - Phorbol 12-myristate 13-acetate (PMA) increased 1,25(OH)(2)D(3)-induced human 25
      hydroxyvitamin d-24 hydroxylase (hCYP24A1) gene expression and vitamin D receptor
      (VDR) binding to the hCYP24A1 promoter. It did not alter transient receptor
      potential cation channel, subfamily V, member 6 (TRPV6) expression, VDR binding
      to the TRPV6 promoter, or VDR binding to a crude chromatin preparation. PMA
      activated Extracellular signal-Regulated Kinases (ERK) 1/2 and p38 mitogen
      activated protein kinases (MAPK) and inhibiting these kinases reduced
      1,25(OH)(2)D(3)-induced and PMA-enhanced hCYP24A1 promoter activity. Mithramycin
      A inhibits Specific Protein (Sp) family member binding to DNA and reduced
      1,25(OH)(2)D(3)-induced and PMA-enhanced hCYP24A1 promoter activity. Sp1 or Sp3
      siRNA knockdown reduced 1,25(OH)(2)D(3)-regulated hCYP24A1 promoter activity but
      only Sp3 siRNA reduced PMA-enhanced hCYP24A1 promoter activity. PMA increased
      MAPK-dependent Sp3 phosphorylation, Sp3-VDR interactions, and Sp3 binding to the
      hCYP24A1 promoter. These data suggest that MAPK signaling contributes to
      1,25(OH)(2)D(3)-induced and PMA-enhanced CYP24A1 gene transcription by modulating
      Sp3 function.

PMID- 22871969
TI  - Motor system: Getting ready to reach.

PMID- 22871971
TI  - Metabolism: Why high-protein diets work.

PMID- 22871974
TI  - Retraction. Ventricular ectopic beats: an overview of management considerations.

PMID- 22871973
TI  - Acoustofluidics 18: Microscopy for acoustofluidic micro-devices.
AB  - In this tutorial review in the thematic series "Acoustofluidics", we discuss the
      implementation and practice of optical microscopy in acoustofluidic micro
      devices. Examples are given from imaging of acoustophoretic manipulation of
      particles and cells in microfluidic channels, but most of the discussion is
      applicable to imaging in any lab-on-a-chip device. The discussion includes basic
      principles of optical microscopy, different microscopy modes and applications,
      and design criteria for micro-devices compatible with basic, as well as advanced,
      optical microscopy.

PMID- 22871976
TI  - First principles study of oxygen adsorption on Se-modified Ru nanoparticles.
AB  - We present here the results of our density-functional-theory-based calculations
      of the electronic and geometric structures and energetics of  Se and O adsorption
      on Ru 93- and 105-atom nanoparticles. These studies have been inspired by the
      fact that Se/Ru nanoparticles are considered promising electrocatalysts for the
      oxygen reduction reaction (ORR) on direct methanol fuel cell cathodes and the
      oxygen binding energy is a descriptor for the catalyst activity toward this
      reaction. We find the character of chemical bonding of Se on a flat nanoparticle
      facet to be ionic, similar to that obtained earlier for the Se/Ru(0001) surface,
      while in the case of a low-coordinated Ru configuration there is an indication of
      some covalent contribution to the bonding leading to an increase in Se binding
      energy. Se and O co-adsorbed on the flat facet both accept electronic charge from
      Ru, whereas the adsorption on low-coordinated sites causes more complicated
      valence charge redistribution. The Se modification of the Ru particles leads to
      weakening of the oxygen bonding to the particles. However, overall, O binding
      energies are found to be higher for the particles than for Se/Ru(0001). The high
      reactivity of the Se/Ru nanoparticles found in this work is not favorable for
      ORR. We thus expect that larger particles with well-developed flat facets will be
      more efficient ORR catalysts than small nanoparticles with a large fraction of
      under-coordinated adsorption sites.

PMID- 22871975
TI  - Effect of the VKORC1 D36Y variant on warfarin dose requirement and
      pharmacogenetic dose prediction.
AB  - Pharmacogenetic dosing algorithms help predict warfarin maintenance doses, but
      their predictive performance differs in different populations, possibly due to
      unsuspected population-specific genetic variants. The objectives of this study
      were to quantify the effect of the  VKORC1  D36Y variant (a marker of warfarin
      resistance previously described in 4% of Ashkenazi Jews) on warfarin maintenance
      doses and to examine how this variant affects the performance of the
      International Warfarin Pharmacogenetic Consortium (IWPC) dose prediction model.
      In 210 Israeli patients on chronic warfarin therapy recruited at a tertiary care
      centre, we applied the IWPC model and then added D36Y genotype as covariate to
      the model (IWPC+D36Y) and compared predicted with actual doses. Median weekly
      warfarin dose was 35 mg (interquartile range [IQR], 24.5 to 52.5 mg). Among 16
      heterozygous D36Y carriers (minor allele frequency = 3.8%), warfarin weekly dose
      was increased by a median of 43.7 mg (IQR, 40.5 to 47.2 mg) compared to non
      carriers after adjustment for all IWPC parameters, a greater than two-fold dose
      increase. The IWPC model performed suboptimally (coefficient of determination
      R2=27.0%; mean absolute error (MAE), 14.4 +/- 16.2 mg/week). Accounting for D36Y
      genotype using the IWPC+D36Y model resulted in a significantly better model
      performance (R2=47.2%, MAE=12.6 +/- 12.4 mg/week). In conclusion, even at low
      frequencies, variants with a strong impact on warfarin dose may greatly decrease
      the performance of a commonly used dose prediction model. Unexpected
      discrepancies of the performance of universal prediction models in subpopulations
      should prompt searching for unsuspected confounders, including rare genetic
      variants.

PMID- 22871977
TI  - Modularity in signaling systems.
AB  - Modularity is a property by which the behavior of a system does not change upon
      interconnection. It is crucial for understanding the behavior of a complex system
      from the behavior of the composing subsystems. Whether modularity holds in
      biology is an intriguing and largely debated question. In this paper, we discuss
      this question taking a control system theory view and focusing on signaling
      systems. In particular, we argue that, despite signaling systems being
      constituted of structural modules, such as covalent modification cycles,
      modularity does not hold in general. As in any engineering system, impedance-like
      effects, called retroactivity, appear at interconnections and alter the behavior
      of connected modules. We further argue that while signaling systems have evolved
      sophisticated ways to counter-act retroactivity and enforce modularity,
      retroactivity may also be exploited to finely control the information processing
      of signaling pathways. Testable predictions and experimental evidence are
      discussed with their implications.

PMID- 22871978
TI  - The effects of osteoclast modifiers on the oral cavity:  a review for
      prescribers.
AB  - PURPOSE OF REVIEW: Osteonecrosis of the jaw associated with therapeutic
      osteoclast modifiers is a rare but serious event. The consequences of
      osteonecrosis can be devastating despite current treatment. With the increase in
      diversity of agents and significant increase in the prevalence of osteoclast
      modifiers prescribed by oncologists understanding diagnosis and management of
      osteoclast modifiers-related osteonecrosis of the jaws (OMRONJ) is necessary. The
      risk of osteonecrosis when osteoclast modifiers are used for management of
      osteoporosis is much less than osteoclast modifiers used in the oncology setting.
      A basic understanding of the oral exam and current management will lead to more
      effective communication and more effective prevention of devastating OMRONJ.
      RECENT FINDINGS: An indistinguishable rate of ONJ seen with new therapeutic
      agents is becoming apparent and relevant preventive therapy and counseling of the
      patient is indicated. Currently there is no comprehensive clinical guideline that
      unifies oncologists and oral health providers in the prevention and management of
      OMRONJ. SUMMARY: Communication and proper planning with each patient's provider
      is the most effective strategy to prevent OMRONJ. A team composed of an
      oncologist, oral and maxillofacial surgeon and dentist competent in managing this
      condition is necessary. An understanding of the cause and development of OMRONJ
      can give the prescriber an improved perspective to communicate with oral health
      professional colleagues. Current guidelines emphasize the need for dental
      management prior to the use of osteoclast modifiers for the prevention and
      management of osteonecrosis of the jaw.

PMID- 22871979
TI  - Multiple myeloma:  improved outcomes with new therapeutic approaches.
AB  - PURPOSE OF REVIEW: Nearly all patients with multiple myeloma will eventually
      relapse; and, thus, it is critical to identify new treatments that increase
      therapeutic options for these patients. This review highlights the newest
      approaches with already approved drugs for treating this common B-cell
      malignancy. RECENT FINDINGS: Most patients with multiple myeloma in both the
      frontline and relapsed/refractory settings are now treated with a combination of
      dexamethasone with the proteasome inhibitor bortezomib and/or an immunomodulatory
      agent thalidomide or lenalidomide. However, alkylating agents including
      melphalan, cyclophosphamide and most recently bendamustine as well as
      anthracyclines, especially the pegylated liposomal doxorubicin, have shown high
      response rates and prolonged remissions when combined with these agents. There
      are emerging data showing the importance of maintenance therapy especially with
      lenalidomide. Because of the marked improvement in survival of multiple myeloma
      during the past decade, there has been a renewed emphasis on developing therapies
      that are not only effective but also well tolerated. Alternative dosing,
      scheduling and routes of administration of already approved drugs have proven
      effective in accomplishing these goals. SUMMARY: The availability of drugs with
      different mechanisms that produce anti-multiple myeloma effects and also show
      synergistic effects has paved the way for more effective and safer combinations
      and led to multiple myeloma patients living longer with improved quality of
      lives.

PMID- 22871980
TI  - The challenge of international consensus:  defining an opioid essential
      prescription package.
AB  - PURPOSE OF REVIEW: To describe a new strategy that aimed to facilitate opioid
      prescription for better pain management. RECENT FINDINGS: The International
      Association of Hospice and Palliative Care recently develop a single prescription
      package (drugs and dosing) with one opioid, one laxative, and one antiemetic for
      the initiation of opioid treatment in cancer pain and other life-threatening
      conditions, with the intention to facilitate opioid use, improve patient
      compliance, and reduce adverse effects. SUMMARY: The opioid essential
      prescription package was an international project designed to ensure that opioids
      are better tolerated by reducing the adverse effects of opioids, which could lead
      to more sustained improvements in pain management.

PMID- 22871981
TI  - Challenges in end-of-life communication.
AB  - PURPOSE OF REVIEW: The purpose of this review is to give an overview of
      challenges that have been addressed in recent research in end-of-life
      communication. RECENT FINDINGS: Diversity of difficulties that may occur in
      communication about end-of-life issues has been showed. The emotional quality of
      this communication requires special skills from professionals involved. Studies
      showed that physicians and medical students are often overstrained and avoid end
      of-life discussions. Health professionals and patients are often ambivalent about
      end-of-life discussions. Nevertheless, professionals are expected to initiate
      these in an honest, needs-oriented way. Patient preferences are difficult to
      infer and have to be assessed explicitly and regularly. Studies showed that the
      emotional impact of end-of-life discussions can lead to a high burden or
      avoidance of professionals. Interdisciplinary, multi-professional work can
      support health professionals in end-of-life care but often structural barriers
      obstruct possible benefits. SUMMARY: Health professionals need to initiate end-of
      life communication in a sensitive way. Specific demands for health professionals
      in end-of-life communication are to differentiate own emotions and life events
      from those of patients and to deal with both adequately. Moreover, structural
      aspects can lead to difficulties between different specialties, professions and
      sectors, which can have a negative impact on adequate care for patient and
      relatives. Special efforts for improvement are needed.

PMID- 22871982
TI  - Preventing bone complications in prostate cancer.
AB  - PURPOSE OF REVIEW: Bone metastases alone or in combination with androgen
      deprivation therapy-related bone loss places prostate cancer patients at greater
      risk for skeletal morbidities, including pain, pathologic fracture and spinal
      cord compression. These events significantly impair the patient's quality of life
      and place a significant burden on health-care resources. RECENT FINDINGS: This
      review focuses on the management options for reducing skeletal morbidity in
      patients with prostate cancer, including life-style modifications, food
      supplementation, osteoclast-targeted therapy and selective estrogen-receptor
      modulators. SUMMARY: The use of osteoclast-targeted therapy (denosumab and
      zoledronic acid) is supported by the strongest evidence and has been US Food and
      Drug Administration-approved for the treatment of patients with PCa at high risk
      of osteoporotic fractures and for the reduction of the risk of skeletal-related
      events in patients with castration-resistant prostate cancer. Ongoing trials are
      studying the potential role of osteoclast-targeted therapy in other settings
      throughout the course of the disease.

PMID- 22871984
TI  - New tetramethylthiepinium (TMTI) for copper-free click chemistry.
AB  - A new derivative of the strained 3,3,6,6-tetramethylthiacycloheptyne (TMTH)
      bearing a functional handle is reported. Following an optimized synthesis, the
      handle was introduced by mild alkylation of the sulphur atom. The resulting
      functionalized strained 4,5-didehydro-3,3,6,6-tetramethyl-2,3,6,7
      tetrahydrothiepinium (TMTI) proved to be stable and underwent extremely fast
      [3+2] cycloaddition reaction with benzyl azide in both organic and aqueous
      solvents. The reaction was equally efficient in cell lysate and serum and
      therefore opens interesting prospects for chemical-biology applications.

PMID- 22871983
TI  - Determinants of the intention of preconception care use: lessons from a multi
      ethnic urban population in the Netherlands.
AB  - OBJECTIVES: To investigate the determinants of the intention of preconception
      care use of women in a multi-ethnic urban population. METHODS: The ASE-model-a
      health behaviour model-was used as an explanatory framework. A representative
      sample was taken from the municipal population registers of two districts in
      Rotterdam, the Netherlands, 2009-2010. 3,225 women (aged 15-60 years) received a
      questionnaire, which was returned by 631: 133 Dutch, 157 Turkish and Moroccan,
      and 341 Surinamese and Antillean. Descriptive, univariate and multivariate
      analyses were performed. RESULTS: The multiple logistic analyses showed that
      intention to attend preconception care was significantly higher in women with a
      Turkish and Moroccan background (beta 1.02, P = 0.006), a higher maternal age
      (beta 0.04, P = 0.008) and a positive attitude (beta 0.50, P < 0.001). Having no
      relationship (beta -1.16, P = 0.004), multiparity with previous adverse perinatal
      outcome (beta -1.32, P = 0.001), a high educational level (beta -1.23, P = 0.03),
      having paid work (beta -0.72, P = 0.01) and experienced barriers level (beta 
      0.15, P = 0.003) were associated with less intention to use preconception care.
      CONCLUSIONS: Modifiable determinants as attitude and barriers can be addressed to
      enhance preconception care attendance.

PMID- 22871985
TI  - Lectin-array blotting: profiling protein glycosylation in complex mixtures.
AB  - By combining electrophoretic protein separation with lectin-array-based glycan
      profiling into a single experiment, we have developed a high-throughput method
      for the rapid analysis of protein glycosylation in biofluids. Fluorescently
      tagged proteins are separated by SDS-PAGE and transferred by diffusion to a
      microscope slide covered with multiple copies of 20 different lectins, where they
      are trapped by specific carbohydrate protein interactions while retaining their
      relative locations on the gel. A fluorescence scan of the slide then provides an
      affinity profile with each of the 20 lectins containing a wealth of structural
      information regarding the present glycans. The affinity of the employed lectins
      toward N-glycans was verified on a glycan array of 76 structures. While current
      lectin-based methods for glycan analysis provide only a picture of the bulk
      glycosylation in complex protein mixtures or are focused on a few specific known
      biomarkers, our array-based glycoproteomics method can be used as a biomarker
      discovery tool for the qualitative exploration of protein glycosylation in an
      unbiased fashion.

PMID- 22871986
TI  - A side-effect induced by the combination of a demineralized freeze-dried bone
      allograft and leucocyte and platelet-rich plasma during treatment for large bone
      cysts: a 4-year follow-up clinical study.
AB  - During platelet activation over 30 growth factors are released from their alpha
      granules. By concentrating platelets, higher levels of growth factors are
      obtained and can be used to stimulate the healing processes. Moreover, during
      blood centrifugation, huge numbers of leukocytes and thrombocytes can be obtained
      to form leukocyte and platelet-rich plasma (L-PRP). After platelet degranulation
      the active gelatinous matrix called leukocyte and platelet-rich gel (L-PRG) is
      formed. In the present clinical study, we report the influence of PLRG and freeze
      dried allografts on healing of large femoral bone cysts. Each of 6 participants
      was followed on a regular basis with clinical examinations, roentgenograms and
      dual-energy X-ray absorptiometry (DXA) examinations. Our four-year follow up
      clinical study using allografts and PLRG in the treatment of large cystic lesions
      of the proximal femur showed that mixing these substances is not efficient and it
      might induce unknown local reactions between them causing complete bone graft
      destruction. Further studies are necessary to fully understand the mechanisms of
      the local activity of L-PRP gel.

PMID- 22871987
TI  - Combination of in situ split and portal ligation:  lights and shadows of a new
      surgical procedure.

PMID- 22871988
TI  - United States Military Cancer Institute Clinical Trials Group (USMCI GI-01)
      randomized controlled trial comparing targeted nodal assessment and ultrastaging
      with standard pathological evaluation for colon cancer.
AB  - OBJECTIVE: Our randomized controlled trial previously demonstrated improved
      staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in
      colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves
      disease-free survival (DFS) in CC. METHODS: In this randomized trial, targeted
      nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic
      yield associated with improved staging accuracy, which was further associated
      with improved disease-free survival in early colon cancer. RESULTS: Clinical
      parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable.
      Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16
      (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months.
      Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P =
      0.11). Clinical parameters of node-negative patients in the control (n = 51) and
      TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us
      arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly
      between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04).
      Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%;
      P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us
      stratified CC prognosis; DFS differed significantly between ultrastaged and
      conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-)
      87%; P = 0.03]. Survival varied according to lymph node yield in patients with
      node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P =
      0.011] but not in stage III CC. CONCLUSIONS: TNA-us is associated with improved
      nodal diagnostic yield and enhanced staging accuracy (stage migration), which is
      further associated with improved DFS in early CC. This study is registered at
      clinicaltrials.gov under the registration number: NCT01623258.

PMID- 22871989
TI  - Structure-property relations and thermodynamic properties of monoclinic petalite,
      LiAlSi4O10.
AB  - Structure-property relations of monoclinic petalite, LiAlSi(4)O(10), were
      determined by experiment and atomistic modeling based on density functional
      theory. The elastic stiffness coefficients were measured between room temperature
      and 570 K using a combination of the plate-resonance technique and resonant
      ultrasound spectroscopy. The thermal expansion was studied between 100 and 740 K
      by means of dilatometry. The heat capacity between 2 and 398 K has been obtained
      by microcalorimetry using a quasi-adiabatic calorimeter. The experimentally
      determined elastic stiffness coefficients were employed to benchmark the results
      of density functional theory based model calculations. The values in the two data
      sets agreed to within a few GPa and the anisotropy was very well reproduced. The
      atomistic model was then employed to predict electric field gradients, the
      lattice dynamics and thermodynamic properties. The theoretical charge density was
      analyzed to investigate the bonding between atoms.

PMID- 22871990
TI  - An investigation of the factor structure and convergent and discriminant validity
      of the five-factor model rating form.
AB  - The Five-Factor Model Rating Form (FFMRF) is a one-page measure designed to
      provide an efficient assessment of the higher order domains of the Five Factor
      Model (FFM) as well as the more specific, lower order facets proposed by McCrae
      and Costa. Although previous research has suggested that the FFMRF's assessment
      of the lower order facets converge reasonably with other FFM measures, the
      structural validity of the domain-level assessment has not yet been evaluated.
      The current study employed an exploratory structural equation modeling framework
      to investigate the fit of a five-factor solution within a combined sample of 757
      participants. This was a novel analysis using a combined sample drawn from three
      previously published studies and was composed primarily of undergraduates but
      also included a smaller clinical subsample. Results indicated that the FFMRF is
      well accommodated within a five-factor solution. Furthermore, the FFMRF domain
      scores evinced large correlations with domain scores from the NEO Personality
      Inventory-Revised. The results suggest that the FFMRF might hold promise as a
      choice for those seeking a brief measure that provides a valid assessment of both
      the broad and specific traits of the FFM.

PMID- 22871991
TI  - Approximating the dynamics of communicating cells in a diffusive medium by ODEs
      homogenization with localization.
AB  - Bacteria may change their behavior depending on the population density. Here we
      study a dynamical model in which cells of radius [R] within a diffusive medium
      communicate with each other via diffusion of a signalling substance produced by
      the cells. The model consists of an initial boundary value problem for a
      parabolic PDE describing the exterior concentration [u] of the signalling
      substance, coupled with [N] ODEs for the masses [ai] of the substance within each
      cell. We show that for small [R] the model can be approximated by a hierarchy of
      models, namely first a system of [N] coupled delay ODEs, and in a second step by
      [N] coupled ODEs. We give some illustrations of the dynamics of the approximate
      model.

PMID- 22871992
TI  - Effective treatment of squamous cell carcinomas with ingenol mebutate gel in
      immunologically intact SKH1 mice.
AB  - Ingenol mebutate has recently been approved by the Federal Drug Administration
      (USA) as a topical treatment for actinic keratoses. Herein, we describe the
      efficacy of ingenol mebutate for the topical treatment of squamous cell carcinoma
      (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell
      line, T7. Daily treatment for 2 days with 0.25 % ingenol mebutate gel produced a
      cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed
      swelling of cancer cell mitochondria within 1 h, with disruption of the inner
      mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer
      cells was clearly evident by 24 h. Treatment was associated with local
      haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also
      detected. This is the first report of the successful treatment of SCC tumours
      with ingenol mebutate gel in wild-type mice, and supports the view that ingenol
      mebutate induces primary necrosis and activates the immune system.

PMID- 22871993
TI  - Subtoxic levels hydrogen peroxide-induced expression of interleukin-6 by
      epidermal melanocytes.
AB  - Oxidative stress and autoimmune reaction are involved in the pathogenesis of
      vitiligo. Levels of hydrogen peroxide (H(2)O(2)) and interleukin-6 (IL-6), a
      proinflammation cytokine and a key factor in the pathogenesis of autoimmune
      diseases, have been reported to be elevated in vitiligo lesions. The objective of
      this study was to evaluate the effects of subtoxic levels of H(2)O(2) on the
      expression of IL-6 by cultured human epidermal melanocytes and to explore the
      relevant signal pathways. Cultured human melanocytes were stimulated with of
      H(2)O(2) at subtoxic levels. Levels of IL-6 protein in the medium and IL-6 mRNA
      in the cells were measured by IL-6 ELISA analysis and RT-PCR, respectively. NF
      kappaB and phosphorylated p38 mitogen-activated protein kinase (MAPK), ERK and
      JNK in cells cultured with and without H(2)O(2) were measured by relevant ELISA
      kits. In cultured melanocytes, subtoxic levels of H(2)O(2) (30-300 MUM)
      significantly increased the IL-6 mRNA and protein levels in a dose-dependent
      manner. NF-kappaB in nuclear extracts and phosphorylated p38 MAPK levels in cell
      lysates were significantly increased in H(2)O(2) treated cells. Pretreatment of
      cells with inhibitors of p38 MAPK (SB203580) and NF-kappaB (BAY11-7082), but not
      inhibitors of ERK (UO1026) and JNK (SP600125), abolished H(2)O(2)-induced
      expression of IL-6. H(2)O(2)-induced overexpression of IL-6 by melanocytes may be
      a molecular linkage for the oxidative stress and inflammatory/autoimmune
      reactions in vitiligo and may provide a novel target for the treatment of
      vitiligo.

PMID- 22871995
TI  - In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose
      requirements and clearance in renal transplant patients.
AB  - Tacrolimus is metabolized by CYP3A4 and CYP3A5 and is characterized by a narrow
      therapeutic index and highly variable pharmacokinetics. This cross-sectional
      study in 59 renal transplant patients investigated the relationship among in vivo
      CYP3A4 activity (assessed using midazolam as a drug probe), CYP3A5 genotype on
      the one hand, and tacrolimus pharmacokinetics on the other hand, taking into
      account other potential determinants of tacrolimus disposition. In vivo CYP3A4
      activity and CYP3A5 genotype explain 56-59% of variability in tacrolimus dose
      requirements and clearance, contributing ~25 and 30%, respectively. Hematocrit
      explains an additional 4-14%. These data indicate that CYP3A4- and CYP3A5
      mediated tacrolimus metabolisms are major determinants of tacrolimus disposition
      in vivo and explain a substantial part of the clinically observed high
      interindividual variability in tacrolimus pharmacokinetics. Furthermore, these
      data provide a potential basis for a comprehensive approach to predicting
      tacrolimus dose requirement in individual patients and hence provide a strategy
      to tailor immunosuppressive therapy in transplant recipients.

PMID- 22871994
TI  - Nrf2: a potential target for new therapeutics in liver disease.
AB  - Nuclear erythroid 2-related factor 2 (Nrf2) is an oxidative stress-mediated
      transcription factor with a variety of downstream targets aimed at
      cytoprotection. Nrf2 has recently been implicated as a new therapeutic target for
      the treatment of liver disease. Here, we focus on the most common liver diseases
      nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease, and
      drug-induced liver injury-and highlight areas in the development of these
      conditions where activation of Nrf2 may alleviate disease progression.

PMID- 22871996
TI  - International vision and strategy for drug regulatory authority: the PMDA's
      international vision.
AB  - The past several years saw various countries' drug regulatory authorities (DRAs)
      internationalizing their activities in response to the rapid globalization of
      pharmaceutical affairs. This is the second surge of internationalization, coming
      after the first in the 1990s, when the International Conference on Harmonisation
      (ICH) and the Global Harmonization Task Force were founded. For maximum effect, a
      DRA needs to carefully strategize its international activities. The significance
      of international master plans is discussed in relation to the recently published
      International Vision of Japan's Pharmaceuticals and Medical Devices Agency
      (PMDA).

PMID- 22871997
TI  - Alanine aminotransferase: a clinical and regulatory tool for detecting liver
      injury-past, present, and future.
AB  - Assay of the serum activity of the enzyme alanine aminotransferase (ALT) has
      become the primary screening tool for detecting acute liver injury. But what does
      an elevated value mean? Not what it is too often mistakenly believed to indicate.
      It is not a test of liver function. It does not necessarily predict worse effects
      to come (in a given person). It is not a valid measure of severity of liver
      injury or dysfunction. It is too unspecific to be reliable in screening for
      relatively rare effects on the liver. Although these are substantial limitations,
      ALT is a very useful biomarker if understood and used properly. It is important
      to consider how and why these erroneous concepts came to have such wide
      acceptance, and how elevations of ALT activity for evaluating patients and
      subjects under study might be interpreted better.

PMID- 22871998
TI  - Ammonia-lowering strategies for the treatment of hepatic encephalopathy.
AB  - Hyperammonemia leads to neurotoxic levels of brain ammonia and is a major factor
      involved in the pathogenesis of hepatic encephalopathy (HE). Ammonia-lowering
      treatments primarily involve two strategies: inhibiting ammonia production and/or
      increasing ammonia removal. Targeting the gut has been the primary focus for many
      years, with the goal of inhibiting the generation of ammonia. However, in the
      context of liver failure, extrahepatic organs containing ammonia metabolic
      pathways have become new potential ammonia-lowering targets. Skeletal muscle has
      the capacity to remove ammonia by producing glutamine through the enzyme
      glutamine synthetase (amidation of glutamate) and, given its large mass, has the
      potential to be an important ammonia-removing organ. On the other hand, glutamine
      can be deaminated to glutamate by phosphate-activated glutaminase, thus releasing
      ammonia (ammonia rebound). Therefore, new treatment strategies are being focused
      on stimulating the removal of both ammonia and glutamine.

PMID- 22872000
TI  - pi-Depletion as a criterion to predict pi-stacking ability.
AB  - The screening of molecular targets benefits from design criteria, which can
      identify the most promising candidates. We demonstrate that pi-depleted
      polyaromatic molecules present superior pi-stacking ability. This realization is
      quantified using a computational criterion, LOLIPOP, that detects ideal pi
      conjugated frameworks. The utility of LOLIPOP is illustrated by identifying
      tailored chemosensors.

PMID- 22871999
TI  - Concordance of DMET plus genotyping results with those of orthogonal genotyping
      methods.
AB  - There are several hurdles to the clinical implementation of pharmacogenetics. One
      approach is to employ pre-prescription genotyping, involving interrogation of
      multiple pharmacogenetic variants using a high-throughput platform. We compared
      the performance of the Drug Metabolizing Enzymes and Transporters (DMET) Plus
      array (1,931 variants in 225 genes) with that of orthogonal genotyping methods in
      220 pediatric patients. A total of 1,692 variants had call rates >98% and were in
      Hardy-Weinberg equilibrium. Of these, 259 were genotyped by at least one
      independent method, and a total of 19,942 single-nucleotide polymorphism (SNP)
      patient sample pairs were evaluated. The concordance rate was 99.9%, with only 28
      genotype discordances observed. For the genes deemed most likely to be clinically
      relevant (TPMT, CYP2D6, CYP2C19, CYP2C9, VKORC1, DPYD, UGT1A1, and SLCO1B1), a
      total of 3,799 SNP-patient sample pairs were evaluable and had a concordance rate
      of 99.96%. We conclude that the DMET Plus array performs well with primary
      patient samples, with the results in good concordance with those of several lower
      throughput genotyping methods.

PMID- 22872001
TI  - Locomotion scores and lying behaviour are indicators of hoof lesions in dairy
      cows.
AB  - Locomotion scoring, lying behaviour and lesion recording during hoof trimming are
      all ways of evaluating hoof health in dairy cows. The objective of this study was
      to evaluate the relationship between these measures in a random sample of 1340
      cows from 42 Danish dairy herds. The hypothesis was that locomotion scoring
      and/or the monitoring of lying behaviour could be used as tools to identify cows
      with hoof lesions, either of the horn or of the skin. Cows were locomotion
      scored, lying behaviour recorded and data on hoof lesions seen during hoof
      trimming collected. The results were analysed using logistic regression with hoof
      lesion as the outcome and locomotion score (1-5), mean duration of lying bouts,
      parity and lactation stage as explanatory variables. This analysis was undertaken
      for all types of lesions, for hoof horn lesions only and for skin lesions only.
      Odds of all hoof lesions and of skin lesions increased with increasing locomotion
      score and increasing mean duration of lying bouts. Odds of horn lesions also
      increased with increasing locomotion score, but there was no significant
      association between horn lesions and the mean duration of lying bouts. It was
      concluded that locomotion scoring and duration of lying bouts may be used as
      tools in the management of hoof health in dairy herds.

PMID- 22872002
TI  - Lameness in cattle: an ongoing concern.

PMID- 22872003
TI  - miRNA as activity markers in Parvo B19 associated heart disease.
AB  - Parvovirus B19 is a frequent virus detected in endomyocardial biopsies of
      patients with clinically suspected myocarditis or dilated cardiomyopathy (DCM).
      Viruses often cause a more symptomatic disease with increased tissue injury if
      they become reactivated. A disease-specific differential expression of microRNAs
      (miRNAs) has been described in the regulation of replicating viruses. Analyzing
      patients with latent and reactivated B19V infection, we found 29 differentially
      regulated miRNAs and, in order to test whether predicted genes are differentially
      expressed, selected mRNAs were tested by TaqMan-QPCR.

PMID- 22872004
TI  - [On the retirement of Prof. Dr. Bernhard Maisch in September 2012].

PMID- 22872006
TI  - Temperature dependence of one-dimensional hydrogen bonding in morpholinium
      hydrogen chloranilate studied by 35Cl nuclear quadrupole resonance and multi
      temperature X-ray diffraction.
AB  - The temperature dependence of (35)Cl NQR frequencies and the spin-lattice
      relaxation times T(1) has been measured in the wide temperature range of 4.2-420
      K for morpholinium hydrogen chloranilate in which a one-dimensional O-HO hydrogen
      bonded molecular chain of hydrogen chloranilate ions is formed. An anomalous
      temperature dependence of the NQR frequencies was analyzed to deduce a drastic
      temperature variation of the electronic state of the hydrogen-bonded molecular
      chain. The hydrogen atom distribution in the OHO hydrogen bond is discussed from
      the results of NQR as well as multi-temperature X-ray diffraction. Above ca. 330
      K, the T(1) showed a steep decrease with an activation energy of ca. 70 kJ mol(
      1) and with an isotope ratio (37)Cl T(1)/(35)Cl T(1) = 0.97 +/- 0.2. The
      orientational change of the z axis of electric field gradient tensor in
      conjunction with the hydrogen transfer between adjacent hydrogen chloranilate
      ions is suggested as a possible relaxation mechanism.

PMID- 22872005
TI  - Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of
      bone substitute in high tibial osteotomy.
AB  - PURPOSE: To evaluate granulocyte colony-stimulating factor (G-CSF) efficacy in
      accelerating bone regeneration following opening-wedge high tibial valgus
      osteotomy for genu varum. METHODS: A phase II trial was conducted for evaluating
      the preoperative administration of G-CSF given at 10 MUg/kg/day for 3 consecutive
      days with an additional half-dose 4 h before the opening-wedge high tibial valgus
      osteotomy. Overall, 12 patients (Group A) received G-CSF treatment, and the
      subsequent 12 patients (Group B) underwent surgery without G-CSF. The osteotomy
      gap was filled by a bone graft substitute. Bone marrow cell (BMC) mobilization
      was monitored by CD34+ve cell and clonogenic progenitor cell analysis. All
      patients underwent a clinical (Lysholm Knee Scale and SF-36) and radiographic
      evaluation preoperatively, as well as at given intervals postsurgery. RESULTS:
      All patients completed the treatment program without major side effects; G-CSF
      was well tolerated. BMC mobilization occurred in all Group A patients, with
      median peak values of circulating CD34+ve cells of 110/MUL (range 29-256).
      Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant
      improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared
      to Group B. At the radiographic evaluation, there was a significant increase in
      osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months
      postsurgery compared to Group B. The computerized tomography scan of the grafted
      area at 2 months postsurgery showed no significant difference in the quality of
      the newly formed bone between the two Groups. CONCLUSIONS: Although the limited
      number of patients does not allow firm conclusions, the study suggests that G-CSF
      can be safely administered preoperatively in subjects undergoing opening-wedge
      high tibial valgus osteotomy; in addition, the clinical, radiographic and CT
      monitoring indicate that G-CSF and/or mobilized BMCs may hasten bone graft
      substitute osseointegration. LEVEL OF EVIDENCE: I.

PMID- 22872007
TI  - Thrombogenic changes in young and old mice upon subchronic exposure to air
      pollution in an urban roadside tunnel.
AB  - Epidemiological studies indicate that elderly persons are particularly
      susceptible to the cardiovascular health complications of air pollution, but
      pathophysiological mechanisms behind the increased susceptibility remain unclear.
      Therefore, we investigated how continuous traffic-related air pollution exposure
      affects haemostasis parameters in young and old mice. Young (10 weeks) and old
      (20 months) mice were placed in an urban roadside tunnel or in a clean
      environment for 25 or 26 days and markers of inflammation and endothelial cells
      or blood platelet activation were measured, respectively. Plasma microvesicles
      and pro/anticoagulant factors were analysed, and thrombin generation analysis was
      performed. Despite elevated macrophage carbon load, tunnel mice showed no overt
      pulmonary or systemic inflammation, yet manifested reduced pulmonary
      thrombomudulin expression and elevated endothelial von Willebrand factor (VWF)
      expression in lung capillaries. In young mice, soluble P-selectin (sP-sel)
      increased with exposure and correlated with soluble E-selectin and VWF. Baseline
      plasma factor VIII (FVIII), sP-sel and VWF were higher in old mice, but did not
      pronouncedly increase further with exposure. Traffic-related air pollution
      markedly raised red blood cell and blood platelet numbers in young and old mice
      and procoagulant blood platelet-derived microvesicle numbers in old animals.
      Changes in coagulation factors and thrombin generation were mild or absent.
      Hence, continuous traffic-related air pollution did not trigger overt lung
      inflammation, yet modified pulmonary endothelial cell function and enhanced
      platelet activity. In old mice, subchronic exposure to polluted air raised
      platelet numbers, VWF, sP-sel and microvesicles to the highest values presently
      recorded, collectively substantiating a further elevation of thrombogenicity,
      already high at old age.

PMID- 22872009
TI  - Effects of multiple enzyme-substrate interactions in basic units of cellular
      signal processing.
AB  - Covalent modification cycles are a ubiquitous feature of cellular signalling
      networks. In these systems, the interaction of an active enzyme with the
      unmodified form of its substrate is essential for signalling to occur. However,
      this interaction is not necessarily the only enzyme-substrate interaction
      possible. In this paper, we analyse the behaviour of a basic model of signalling
      in which additional, non-essential enzyme-substrate interactions are possible.
      These interactions include those between the inactive form of an enzyme and its
      substrate, and between the active form of an enzyme and its product. We find that
      these additional interactions can result in increased sensitivity and biphasic
      responses, respectively. The dynamics of the responses are also significantly
      altered by the presence of additional interactions. Finally, we evaluate the
      consequences of these interactions in two variations of our basic model,
      involving double modification of substrate and scaffold-mediated signalling,
      respectively. We conclude that the molecular details of protein-protein
      interactions are important in determining the signalling properties of enzymatic
      signalling pathways.

PMID- 22872008
TI  - A convenient and general expression platform for the production of secreted
      proteins from human cells.
AB  - Recombinant protein expression in bacteria, typically E. coli, has been the most
      successful strategy for milligram quantity expression of proteins. However,
      prokaryotic hosts are often not as appropriate for expression of human, viral or
      eukaryotic proteins due to toxicity of the foreign macromolecule, differences in
      the protein folding machinery, or due to the lack of particular co- or post
      translational modifications in bacteria. Expression systems based on yeast (P.
      pastoris or S. cerevisiae) (1,2), baculovirus-infected insect (S. frugiperda or
      T. ni) cells (3), and cell-free in vitro translation systems (2,4) have been
      successfully used to produce mammalian proteins. Intuitively, the best match is
      to use a mammalian host to ensure the production of recombinant proteins that
      contain the proper post-translational modifications. A number of mammalian cell
      lines (Human Embryonic Kidney (HEK) 293, CV-1 cells in Origin carrying the SV40
      larget T-antigen (COS), Chinese Hamster Ovary (CHO), and others) have been
      successfully utilized to overexpress milligram quantities of a number of human
      proteins (5-9). However, the advantages of using mammalian cells are often
      countered by higher costs, requirement of specialized laboratory equipment, lower
      protein yields, and lengthy times to develop stable expression cell lines.
      Increasing yield and producing proteins faster, while keeping costs low, are
      major factors for many academic and commercial laboratories. Here, we describe a
      time- and cost-efficient, two-part procedure for the expression of secreted human
      proteins from adherent HEK 293T cells. This system is capable of producing
      microgram to milligram quantities of functional protein for structural,
      biophysical and biochemical studies. The first part, multiple constructs of the
      gene of interest are produced in parallel and transiently transfected into
      adherent HEK 293T cells in small scale. The detection and analysis of recombinant
      protein secreted into the cell culture medium is performed by western blot
      analysis using commercially available antibodies directed against a vector
      encoded protein purification tag. Subsequently, suitable constructs for large
      scale protein production are transiently transfected using polyethyleneimine
      (PEI) in 10-layer cell factories. Proteins secreted into litre-volumes of
      conditioned medium are concentrated into manageable amounts using tangential flow
      filtration, followed by purification by anti-HA affinity chromatography. The
      utility of this platform is proven by its ability to express milligram quantities
      of cytokines, cytokine receptors, cell surface receptors, intrinsic restriction
      factors, and viral glycoproteins. This method was also successfully used in the
      structural determination of the trimeric ebolavirus glycoprotein (5,10). In
      conclusion, this platform offers ease of use, speed and scalability while
      maximizing protein quality and functionality. Moreover, no additional equipment,
      other than a standard humidified CO2 incubator, is required. This procedure may
      be rapidly expanded to systems of greater complexity, such as co-expression of
      protein complexes, antigens and antibodies, production of virus-like particles
      for vaccines, or production of adenoviruses or lentiviruses for transduction of
      difficult cell lines.

PMID- 22872010
TI  - Reward aspects of gastrointestinal hormones mediated by brain G protein-coupled
      receptors.

PMID- 22872011
TI  - Intrastriatal shifts mediate the transition from drug-seeking actions to habits.

PMID- 22872012
TI  - Modafinil-cocaine interactions: clinical implications.

PMID- 22872013
TI  - Depressive symptoms are increased in the early perimenopausal stage in ethnically
      diverse human immunodeficiency virus-infected and human immunodeficiency virus
      uninfected women.
AB  - OBJECTIVE: The risk of clinically significant depressive symptoms increases
      during perimenopause. With highly active antiretroviral treatment (HAART), more
      human immunodeficiency virus (HIV)-infected women survive to transition through
      menopause. In a cross-sectional analysis, we evaluated the association of
      menopausal stage and vasomotor symptoms with depressive symptoms in an ethnically
      diverse cohort of women with a high prevalence of HIV. METHODS: Participants
      included 835 HIV-infected women and 335 HIV-uninfected controls from the Women's
      Interagency HIV Study (63% African American). The Center for Epidemiologic
      Studies Depression Scale was used to screen for elevated depressive symptoms.
      Menopausal stages were defined according to standard definitions. Logistic
      regression analysis was used to identify predictors of elevated depressive
      symptoms. RESULTS: Compared with premenopausal women, early perimenopausal women
      (OR [odds ratio], 1.74; 95% CI, 1.17-2.60), but not late perimenopausal or
      postmenopausal women, were more likely to show elevated depressive symptoms in
      adjusted analyses. The odds were similar in HIV-infected and HIV-uninfected
      women. Persistent vasomotor symptoms also predicted elevated depressive symptoms
      in HIV-infected and HIV-uninfected women (OR, 1.45; 95% CI, 1.02-2.06). In HIV
      infected women, menopausal stage interacted with antiretroviral use (P = 0.02);
      the likelihood of elevated depressive symptoms in early perimenopause compared
      with premenopause was especially high in HAART-untreated women (OR, 3.87; 95% CI,
      1.57-9.55). CONCLUSIONS: In HIV-infected and HIV-uninfected women, the odds of
      elevated depressive symptoms were significantly higher during early
      perimenopause. Elevated depressive symptoms were associated with nonadherence to
      HAART, underscoring the importance of screening and treating depressive symptoms
      in HIV-infected women who have experienced a change in the regularity of their
      menstrual cycles.

PMID- 22872015
TI  - On the importance and origin of aromatic interactions in chemistry and
      biodisciplines.
AB  - Aromatic systems contain both sigma- and pi-electrons, which in turn constitute
      sigma- and pi-molecular orbitals (MOs). In discussing the properties of these
      systems, researchers typically refer to the highest occupied and lowest
      unoccupied MOs, which are pi MOs. The characteristic properties of aromatic
      systems, such as their low ionization potentials and electron affinities, high
      polarizabilities and stabilities, and small band gaps (in spectroscopy called the
      N -> V1 space), can easily be explained based on their electronic structure.
      These one-electron properties point to characteristic features of how aromatic
      systems interact with each other. Unlike hydrogen bonding systems, which
      primarily interact through electrostatic forces, complexes containing aromatic
      systems, especially aromatic stacked pairs, are predominantly stabilized by
      dispersion attraction. The stabilization energy in the benzene dimer is rather
      small (~2.5 kcal/mol) but strengthens with heteroatom substitution. The stacked
      interaction of aromatic nucleic acid bases is greater than 10 kcal/mol, and for
      the most stable stacked pair, guanine and cytosine, it reaches approximately 17
      kcal/mol. Although these values do not equal the planar H-bonded interactions of
      these bases (~29 kcal/mol), stacking in DNA is more frequent than H-bonding and,
      unlike H-bonding, is not significantly weakened when passing from the gas phase
      to a water environment. Consequently, the stacking of aromatic systems represents
      the leading stabilization energy contribution in biomacromolecules and in related
      nanosystems. Therefore stacking (dispersion) interactions predominantly determine
      the double helical structure of DNA, which underlies its storage and transfer of
      genetic information. Similarly, dispersion is the dominant contributor to
      attractive interactions involving aromatic amino acids within the hydrophobic
      core of a protein, which is critical for folding. Therefore, understanding the
      nature of aromatic interactions, which depend greatly on quantum mechanical (QM)
      calculations, is of key importance in biomolecular science. This Account shows
      that accurate binding energies for aromatic complexes should be based on
      computations made at the (estimated) CCSD(T)/complete basis set limit (CBS) level
      of theory. This method is the least computationally intensive one that can give
      accurate stabilization energies for all common classes of noncovalent
      interactions (aromatic-aromatic, H-bonding, ionic, halogen bonding, charge
      transfer, etc.). These results allow for direct comparison of binding energies
      between different interaction types. Conclusions based on lower-level QM
      calculations should be considered with care.

PMID- 22872014
TI  - Linkage analysis for plasma amyloid beta levels in persons with hypertension
      implicates Abeta-40 levels to presenilin 2.
AB  - Plasma concentrations of Abeta40 and Abeta42 rise with age and are increased in
      people with mutations that cause early-onset Alzheimer's disease (AD). Amyloid
      beta (Abeta) plasma levels were successfully used as an (endo)phenotype for gene
      discovery using a linkage approach in families with dominant forms of disease.
      Here, we searched for loci involved in Abeta plasma levels in a series of non
      demented patients with hypertension in the Erasmus Rucphen Family study. Abeta40
      and Abeta42 levels were determined in 125 subjects with severe hypertension. All
      patients were genotyped with a 6,000 single nucleotide polymorphisms (SNPs)
      illumina array designed for linkage analysis. We conducted linkage analysis of
      plasma Abeta levels. None of the linkage analyses yielded genome-wide significant
      logarithm of odds (LOD) score over 3.3, but there was suggestive evidence for
      linkage (LOD > 1.9) for two regions: 1q41 (LOD = 2.07) and 11q14.3 (LOD = 2.97),
      both for Abeta40. These regions were followed up with association analysis in the
      study subjects and in 320 subjects from a population-based cohort. For the
      Abeta40 region on chromosome 1, association of several SNPs was observed at the
      presenilin 2 gene (PSEN2) (p = 2.58 * 10(-4) for rs6703170). On chromosome 11q14
      21, we found some association (p = 3.1 * 10(-3) for rs2514299). This linkage
      study of plasma concentrations of Abeta40 and Abeta42 yielded two suggestive
      regions, of which one points toward a known locus for familial AD.

PMID- 22872016
TI  - High-pressure Raman scattering and an anharmonicity study of multiferroic
      wolframite-type Mn0.97Fe0.03WO4.
AB  - A high-pressure Raman scattering study of wolframite-type Mn(0.97)Fe(0.03)WO(4)
      is presented up to 10.4 GPa. The phonon wavenumbers vary linearly with pressure.
      The mode Gruneisen parameters are larger for many bending and lattice modes when
      compared to the stretching modes due to the larger compressibility of Mn(Fe)O(6)
      octahedra when compared to WO(6) octahedra. Combining the pressure-dependent
      Raman data of this work with the temperature-dependent Raman data on this crystal
      previously reported by us has allowed estimation of the temperature-dependent
      pure lattice and intrinsic anharmonic contributions to the observed total Raman
      shifts as a function of temperature. It has been found that the observed unusual
      hardening of the 884, 698 and 674 cm(-1) stretching modes upon heating from 4 to
      about 150-200 K followed by the usual softening above 150-200 K is a result of a
      positive intrinsic anharmonic contribution and a negative pure lattice
      contribution; i.e., up to about 150-200 K the anharmonic contribution surpasses
      the lattice contribution and the total Raman shift is slightly positive whereas
      above 150-200 K the lattice contribution becomes dominant and the Raman bands
      exhibit the usual softening with increasing temperature.

PMID- 22872017
TI  - First description of coronary artery ostial atresia with fistulous origin from a
      normal right ventricle.
AB  - Anomalous origins of both the left and right coronary arteries are rare but have
      been well documented when both arteries arise from the pulmonary trunk (Angelini
      et al., Circulation 105:2449-2454, 2002). An anomalous coronary arterial origin
      from the pulmonary arteries usually involves the left coronary artery (ALCPA) and
      less frequently the right coronary artery (ARCPA). At least three cases have been
      reported in which the right coronary artery arose abnormally from the left
      ventricle (LV), but none have been reported in which both coronary arteries took
      their origin from the right ventricle (Ippisch and Kimball, J Am Soc Echocardiogr
      23:222.e1-222.e2, 2010; Okuyama et al., Jpn Heart J 36:115-118, 1995; Culbertson
      et al., Pediatr Cardiol 16:73-75, 1995). Ostial atresia with anomalous origin of
      a coronary artery from the right ventricle has been described only in pulmonary
      atresia with an intact ventricular septum and a hypoplastic right ventricle. In
      this setting, atresia of both coronary ostia with right ventricular origin of
      both coronary arteries is a rare variant. This report presents a neonate in whom
      the entire coronary arterial system arose from the right ventricle via a single
      fistula with no other intracardiac defects. To the authors' knowledge, this
      anomaly has not been described previously.

PMID- 22872018
TI  - Maternal diclofenac medication in pregnancy causing in utero closure of the fetal
      ductus arteriosus and hydrops.
AB  - This report describes a case of premature closure in utero of the ductus
      arteriosus (DA) diagnosed postnatally in a baby with hydrops and cardiac failure.
      An echocardiogram 6 h postnatally showed marked dilation of the right atrium and
      right ventricle with marked hypertrophy and impaired function, elevated pulmonary
      pressures, a small pericardial effusion, and no flow through the DA. The mother
      was unaware of her pregnancy until she presented in labor, and she had taken
      diclofenac medication in the preceding months. This case and the accompanying
      literature review illustrate the potential fetal and neonatal complications
      resulting from antenatal closure of the DA due to maternal diclofenac medication
      during pregnancy.

PMID- 22872019
TI  - Parvovirus B19 myocarditis causes significant morbidity and mortality in
      children.
AB  - Although parvovirus B19 (PVB19) currently is the most common cause of viral
      myocarditis, limited pediatric data exist. Whereas other viruses infect
      cardiomyocytes, PVB19 targets coronary endothelium, leading to myocardial
      ischemia and dysfunction. A retrospective review investigated patients with
      polymerase chain reaction (PCR)-verified PVB19 myocarditis at Texas Children's
      Hospital and Arkansas Children's Hospital (January 2005 to August 2008). The
      primary end points of the study were transplant-free survival and circulatory
      collapse (death, mechanical support, or transplantation). For the 19 patients
      identified (age, 6 months to 15 years), the most common presenting symptoms were
      respiratory and gastrointestinal. At admission, all the patients demonstrated
      ventricular dysfunction requiring inotropic support (median ejection fraction, 24
      %; median left ventricle end-diastolic diameter [LVEDD] z-score, 4.6). Whereas T
      wave abnormalities were common, ST elevation was evident in five patients (two
      died and three required transplantation). Serum B-type natrietic peptide was
      elevated in all 12 patients tested (range, 348-8,058 pg/ml), and troponin I was
      high in 7 of 9 patients (range, 0.04-14.5 ng/ml). Of the 15 patients with
      circulatory collapse, nine received mechanical support, eight underwent
      successful transplantation, and five died. Only six patients (32 %) experienced
      transplant-free survival, and five patients had full recovery of function at
      discharge. In the transplant-free survival group, ST changes on presenting
      electrocardiography were less likely (p = 0.03), and the admission LVEDD z-score
      tended to be lower (3.3 vs 5.6; p = 0.08). In children, PVB19 myocarditis causes
      significant mortality and morbidity. Although mechanical intervention can support
      patients in the initial stage of decompensated heart failure, patients with PVB19
      myocarditis often demonstrate persistent dysfunction requiring medical therapy
      and transplantation.

PMID- 22872020
TI  - John Hunter (1728-1793) and the earliest description of a double superior vena
      cava and isolation of the left subclavian artery.

PMID- 22872021
TI  - Right ventricular function in Juvenile idiopathic arthritis patients.

PMID- 22872022
TI  - Etanercept normalises left ventricular mass in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Cardiovascular mortality is increased in patients with rheumatoid
      arthritis (RA). RA is associated with an increased left ventricular mass index
      (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities.
      Experimental studies have suggested that tumour necrosis factor alpha (TNFalpha)
      may induce LV hypertrophy. OBJECTIVE: To study the effect of medium-term (3- and
      6-months) treatment with the TNFalpha inhibitor etanercept (ETN) and synthetic
      disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and
      arterial stiffness in patients with RA. METHODS: Consecutive female patients with
      active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included.
      Clinical and biological monitoring, echocardiography and pulse wave velocity
      (PWV) assessment were performed at inclusion and at 3 and 6 months after the
      start of treatment. Paired t tests and multivariate linear regression analysis
      were used. RESULTS: Mean LVMI tended to be higher at baseline in the ETN group
      than in the sDMARD group (96.5+/-19.8 vs 84.3+/-26.8 g/m2; p=0.11 for the ETN and
      sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was
      significantly decreased at 3 and 6 months (-6.3+/-7.6 and -14.2+/-9.3 g/m2;
      p<0.001), with no change from baseline for patients with sDMARD treatment (-2.2+/
      10.9 and -2.7+/-10.2 g/m2, respectively). Blood pressure (BP) and aortic PWV were
      not changed by either treatment. CONCLUSIONS: ETN induced a significant decrease
      in LVMI with medium-term treatment with no change in BP or PWV. TNFalpha may be
      an important factor of LV hypertrophy, which may explain the benefit of TNF
      inhibitors on cardiovascular morbidity and mortality in RA. These results need to
      be confirmed by larger studies and with other TNF inhibitors.

PMID- 22872023
TI  - Histopathological changes in the human posterior cruciate ligament during aging
      and osteoarthritis: correlations with anterior cruciate ligament and cartilage
      changes.
AB  - OBJECTIVES: To determine the histological patterns of posterior cruciate ligament
      (PCL) degeneration during aging and in relation to changes in articular cartilage
      and anterior cruciate ligament (ACL) across the entire adult age spectrum.
      METHODS: Human knee joints (n=120 from 65 donors) were processed within 72 h of
      postmortem. Articular cartilage surfaces were graded macroscopically. Each PCL
      was histologically evaluated for inflammation, mucinous changes, chondroid
      metaplasia, cystic changes and orientation of collagen fibres. The severity of
      PCL degeneration was classified as normal, mild, moderate or severe. PCL scores
      were compared to ACL and cartilage scores from the same knees. RESULTS: All knees
      had intact PCL. Histologically, 6% were normal, 76% showed mild, 12% moderate and
      9% severe degeneration. Fibre disorientation was the most prevalent and severe
      change. Histological grades of PCL and ACL correlated, but significantly fewer
      PCL than ACL showed severe changes. There was a weaker correlation between aging
      and total histological PCL scores (R=0.26) compared to aging and ACL scores
      (R=0.42). ACL scores correlated with cartilage scores (R=0.54) while PCL scores
      increased with the severity of osteoarthritis from grades 0 to III but not
      between osteoarthritis grades III-IV (R=0.32). In knees with ruptured ACL, the
      PCL scores correlated with cartilage scores of the lateral compartment.
      CONCLUSIONS: PCL histopathological changes were less severe than in the ACL. PCL
      degeneration was associated with ACL and cartilage damage. The lack of
      correlation with age indicates independent pathways for PCL versus ACL
      degeneration.

PMID- 22872024
TI  - IL-33 is overexpressed in the inflamed arteries of patients with giant cell
      arteritis.
AB  - OBJECTIVE: To study the expression of interleukin (IL)-33 and to evaluate its
      relationship with macrophage polarisation in artery biopsy specimens from
      patients with giant cell arteritis (GCA). METHODS: IL-33, ST2, p-STAT-6 and
      perivascular IL-1 receptor-associated kinase 1 (p-IRAK1) tissue distribution was
      evaluated by immunohistochemistry. Inducible nitric oxide synthase and CD163 were
      also used by immunohistochemistry to evaluate the M1 and M2 polarisation,
      respectively. Quantitative gene expression analysis of IL-33, T-helper (Th)2
      related transcription factor STAT6, Th2 cytokines (IL-4, IL-5, IL-25) and
      interferon (IFN)-gamma was performed in artery biopsy samples obtained from 20
      patients with GCA and 15 controls. Five additional patients who had received
      prednisone when the temporal artery biopsy was performed were also enrolled.
      RESULTS: IFN-gamma and IL-33 were significantly overexpressed in the inflamed
      arteries of GCA patients. IL-33 overexpression was not accompanied by a
      concomitant increase of Th2 cytokines. Neovessels scattered through the
      inflammatory infiltrates were the main sites of IL-33 expression. The expression
      of IL-33 receptor ST2 and of p-IRAK1 was also increased in GCA patients. Arteries
      from glucocorticoid-treated patients had a lower expression of IL-33. IL-33 was
      accompanied by the expression of p-STAT6 and a clear M2 macrophages polarisation.
      CONCLUSIONS: A role for IL-33 in the inflammation of GCA patients is supported by
      these findings.

PMID- 22872025
TI  - Functional, mesoporous, superparamagnetic colloidal sorbents for efficient
      removal of toxic metals.
AB  - gamma-Fe(2)O(3) incorporated mesoporous silica particles of 50-100 nm size have
      been synthesized which are functionalized with chelating agents of metal ions.
      These particles are water dispersible but aggregate in response to the external
      magnetic field and have been used for high performance and selective removal of
      Cd, Pb, Hg and As.

PMID- 22872026
TI  - Cyclic regulation of LPA3 in human endometrium.
AB  - BACKGROUND: Lysophosphatidic acid (LPA) belongs to the group of lipid messengers,
      which plays a pivotal role in the establishment of implantation via its cellular
      receptor, LPA3. The aims of the present study were to characterize LPA3 mRNA and
      protein in human endometrium during the normal human menstrual cycle. METHODS:
      Forty-three normally cycling volunteers without reproductive disorders were
      randomized to undergo endometrial sampling on a specific cycle day. Samples were
      assessed for relative LPA3 mRNA expression using real-time PCR and for LPA3
      protein using immunohistochemistry and western blot. RESULTS: The expression of
      LPA3 mRNA significantly increased during the early and late secretory phase
      compared with other menstrual phases. LPA3 protein was localized to the
      epithelial and stromal cells and expression levels followed the same pattern as
      for LPA3 mRNA. CONCLUSION: In the normal human menstrual cycle, LPA3 mRNA and
      protein expression also change, indicating that this gene may be related to the
      function of the endometrium.

PMID- 22872027
TI  - Genital tuberculosis in adolescent girls from low socioeconomic status with acute
      ectopic pregnancy presenting at a tertiary care hospital in urban Northern India:
      are we missing an opportunity to treat?
AB  - INTRODUCTION: Predominant etiology of ectopic gestation is tubal damage, notably
      salpingitis, which may be of tubercular etiology. AIMS AND OBJECTIVES: To compare
      the incidence of genital tuberculosis (GTB) in two groups of adolescent patients:
      one undergoing surgery for acute ectopic pregnancy, the other undergoing suction
      evacuation for spontaneous miscarriage and to evaluate GTB as a risk factor for
      ectopic pregnancy in adolescent girls from low socioeconomic status presenting to
      a tertiary care hospital in Northern India. MATERIALS AND METHODS: Prospective
      case-control study with 17 adolescent subjects from low socioeconomic status with
      acute presentation of ectopic pregnancy (group 1, study) undergoing laparotomy
      with 20 adolescent subjects with spontaneous miscarriage (group 2, control)
      undergoing suction evacuation. Subjects were tested for presence of GTB by
      presence of tubercular granuloma and/or positive growth on BACTEC radiometric
      assay from sample obtained from endometrial aspirate and products of conception
      in groups 1 and 2, respectively. RESULTS: Incidence of GTB was 35.29% (6 out of
      17) in the study group compared with 5% in the control group (1 out of 20)
      (P=0.03). CONCLUSION: The sample size of this pilot study is too small to arrive
      at the definite conclusion whether GTB is risk factor for acute ectopic in this
      population of patients. Larger studies are needed to validate this hypothesis.
      However, in the presence of risk factors/suggestive intraoperative findings,
      testing for TB in this set of population presenting with ectopic pregnancy may be
      justified to prevent further morbidity by initiating anti-tubercular therapy in
      high prevalence areas.

PMID- 22872028
TI  - Performance of RT-PCR in the detection of Streptococcus agalactiae in the
      anogenital tract of pregnant women.
AB  - INTRODUCTION: Infection with Group B Streptococcus (GBS) is the most frequent in
      the first weeks of life of a newborn. The identification of pregnant women with
      GBS colonization may reduce neonatal infection. METHODS: This cross-sectional
      study evaluated the performance of real-time polymerase chain reaction (RT-PCR)
      to detect GBS colonization in the anogenital tract of pregnant women. Anogenital
      swabs were collected from 266 pregnant women from December 2010 to August 2011.
      GBS was detected using culture (gold standard) and RT-PCR to determine sip gene
      expression. The presence of DNA was confirmed using betaglobin amplification, and
      the guanidine technique was used for DNA extraction. When results were
      discordant, the test was repeated using conventional PCR. The results were
      evaluated to determine sensitivity, specificity, positive and negative predictive
      values and accuracy. RESULTS: Of the 266 samples collected, 254 were adequate for
      analysis. Prevalence was 28.7% using the gold standard criterion and 38.2% using
      RT-PCR. The comparison of RT-PCR with culture revealed a sensitivity of 89% (95%
      CI 0.81-0.96), specificity of 82% (95% CI 0.76-0.87), positive predictive value
      of 67% (95% CI 0.57-0.76) and negative predictive value of 94% (95% CI 0.91
      0.99). CONCLUSION: Further studies using other DNA extraction techniques,
      targeting other GBS genes and using sample enhancement before RT-PCR should be
      conducted to determine whether the sensitivity and specificity recommended by the
      CDC may be reached using the same thermal cycler.

PMID- 22872029
TI  - Ingesting breakfast meals of different glycaemic load does not alter cognition
      and satiety in children.
AB  - BACKGROUND/OBJECTIVES: The effect of Glycaemic Index (GI) and Load (GL) of
      breakfasts on satiety and aspects of cognitive function in children is
      inconclusive. We aimed to assess if isocaloric breakfasts differing in GL (by
      replacing high-GI carbohydrate foods with dairy protein foods) acutely alter
      cognitive function and satiety in 10- to 12-year-old children. SUBJECTS/METHODS:
      A total of 39 children, aged 11.6+/-0.7 years with body mass index 18.9+/-3.0
      kg/m2 (Mean+/-s.e.) participated in a randomised crossover trial of three
      isocaloric breakfasts (1.3 MJ): high GL (HGL: 7 g protein, 9 g fat, 50 g
      carbohydrate, GL 33); medium GL (MGL: 14 g protein, 9 g fat, 45 g carbohydrate,
      GL 24) and low GL (LGL: 18 g protein, 10 g fat, 38 g carbohydrate, GL 18). Blood
      glucose was recorded using a continuous glucose monitor. Subjective hunger and
      cognitive performance were measured before and hourly after consuming the test
      breakfast via a computer-delivered battery. Ad libitum intake at a buffet lunch
      meal was measured at 3 h at the end of testing. RESULTS: Incremental area under
      the glucose curve (iAUC) was significantly different with HGL>MGL>LGL (P<0.001).
      Glucose concentrations fell below baseline after 83+/-6 min for HGL, 63+/-5 min
      (MGL) and 67+/-5 min (LGL)(P=0.009). Breakfast GL did not significantly alter
      changes in cognitive function or self-reported satiety throughout testing. Energy
      intake at lunch was not significantly different between treatments (HGL 2943+/
      168 kJ; MGL 2949+/-166 kJ; LGL 2993+/-191 kJ). CONCLUSIONS: Reducing breakfast GL
      by replacing carbohydrate with protein does not alter satiety or cognition over 3
      h in 10- to 12-year-old children.

PMID- 22872030
TI  - The influence of probiotic supplementation on gut permeability in patients with
      metabolic syndrome: an open label, randomized pilot study.
AB  - BACKGROUND/OBJECTIVES: Obesity and metabolic disorders are linked to inflammation
      via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers
      inflammation leading to metabolic syndrome (MetS) and contributing to oxidative
      stress. We intended to investigate the effect of Lactobacillus casei Shirota on
      gut permeability, presence of endotoxin and neutrophil function in MetS.
      SUBJECTS/METHODS: Patients with MetS were randomized to receive 3 * 6.5 * 109 CFU
      L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was
      assessed by a differential sugar absorption method and by determination of
      diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate
      assay, neutrophil function and toll-like receptor (TLR) expression by flow
      cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP)
      and soluble CD14 (sCD14) levels. RESULTS: Twenty-eight patients and 10 healthy
      controls were included. Gut permeability was significantly increased in MetS
      compared with controls but did not differ between patient groups. None of the
      patients were positive for endotoxin. LBP and sCD14 levels were not significantly
      different from healthy controls. High-sensitive C-reactive protein and LBP levels
      slightly but significantly increased after 3 months within the probiotics group.
      Neutrophil function and TLR expression did not differ from healthy controls or
      within the patient groups. CONCLUSIONS: Gut permeability of MetS patients was
      increased significantly compared with healthy controls. L. casei Shirota
      administration in the MetS patients did not have any influence on any parameter
      tested possibly due to too-short study duration or underdosing of L. casei
      Shirota.

PMID- 22872031
TI  - Increased intestinal permeability in malnourished patients with liver cirrhosis.
AB  - BACKGROUND/OBJECTIVE: Malnutrition is a prominent feature in liver cirrhosis,
      with deleterious impact on clinical outcome. The objective of this study is to
      investigate whether malnutrition is associated with increased gastrointestinal
      permeability in liver cirrhosis reflected by altered urinary excretion of non
      metabolizable sugar probes. SUBJECTS/METHODS: Patients with advanced liver
      cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was
      determined according to the Subjective Global Assessment. Intestinal permeability
      was assessed by measuring the urinary excretion of orally administered, non
      metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker
      for intestinal permeability and reflects non-carrier-mediated transcellular and
      paracellular transport of the small intestine during the first 5 h. Sucrose
      recovery in urine within the first 5 h reflects gastroduodenal permeability;
      sucralose recovery in urine 5-26 h after consumption reflects colonic
      permeability. RESULTS: Sixty-four patients (56.7+/-10.8 years; 33% female) were
      included in the study. Twenty-one patients were considered well nourished
      according to the Subjective Global Assessment, 23 moderately nourished and 20
      patients severely malnourished; 74% had alcoholic liver disease and 67% had
      cirrhosis stage Child C. Gastroduodenal and colonic permeability was
      significantly increased in patients with liver cirrhosis compared with 63 healthy
      controls (0.23+/-0.22 and 1.37+/-1.42% vs 0.14+/-0.10 and 0.41+/-0.72% in
      controls), but not different between well and malnourished subjects. Small
      intestinal permeability (lactulose/mannitol ratio) was increased in all patients
      (0.069+/-0.055%) and further increased in malnourished patients (0.048+/-0.031%
      vs 0.084+/-0.061%, P=0.004) due to decreased mannitol recovery only. CONCLUSIONS:
      Gastric, small intestinal and even colonic permeability was altogether increased
      in liver cirrhosis, and malnutrition was associated with further increased small
      intestinal permeability indicative of villous atrophy.

PMID- 22872032
TI  - Non-invasive imaging of disseminated candidiasis in zebrafish larvae.
AB  - Disseminated candidiasis caused by the pathogen Candida albicans is a clinically
      important problem in hospitalized individuals and is associated with a 30 to 40%
      attributable mortality(6). Systemic candidiasis is normally controlled by innate
      immunity, and individuals with genetic defects in innate immune cell components
      such as phagocyte NADPH oxidase are more susceptible to candidemia(7-9). Very
      little is known about the dynamics of C. albicans interaction with innate immune
      cells in vivo. Extensive in vitro studies have established that outside of the
      host C. albicans germinates inside of macrophages, and is quickly destroyed by
      neutrophils(10-14). In vitro studies, though useful, cannot recapitulate the
      complex in vivo environment, which includes time-dependent dynamics of cytokine
      levels, extracellular matrix attachments, and intercellular contacts(10, 15-18).
      To probe the contribution of these factors in host-pathogen interaction, it is
      critical to find a model organism to visualize these aspects of infection non
      invasively in a live intact host. The zebrafish larva offers a unique and
      versatile vertebrate host for the study of infection. For the first 30 days of
      development zebrafish larvae have only innate immune defenses(2, 19-21),
      simplifying the study of diseases such as disseminated candidiasis that are
      highly dependent on innate immunity. The small size and transparency of zebrafish
      larvae enable imaging of infection dynamics at the cellular level for both host
      and pathogen. Transgenic larvae with fluorescing innate immune cells can be used
      to identify specific cells types involved in infection(22-24). Modified anti
      sense oligonucleotides (Morpholinos) can be used to knock down various immune
      components such as phagocyte NADPH oxidase and study the changes in response to
      fungal infection(5). In addition to the ethical and practical advantages of using
      a small lower vertebrate, the zebrafish larvae offers the unique possibility to
      image the pitched battle between pathogen and host both intravitally and in
      color. The zebrafish has been used to model infection for a number of human
      pathogenic bacteria, and has been instrumental in major advances in our
      understanding of mycobacterial infection(3, 25). However, only recently have much
      larger pathogens such as fungi been used to infect larva(5, 23, 26), and to date
      there has not been a detailed visual description of the infection methodology.
      Here we present our techniques for hindbrain ventricle microinjection of prim(25)
      zebrafish, including our modifications to previous protocols. Our findings using
      the larval zebrafish model for fungal infection diverge from in vitro studies and
      reinforce the need to examine the host-pathogen interaction in the complex
      environment of the host rather than the simplified system of the Petri dish(5).

PMID- 22872034
TI  - Primary vaginal calculus in a middle-aged woman with mental and physical
      disabilities.
AB  - Vaginal calculi are rarely encountered and are often misdiagnosed as bladder
      calculi because of the difficulty in achieving an appropriate diagnosis. Most
      vaginal calculi result from the presence of a urethrovaginal fistula; those
      occurring in the absence of such fistulas are extremely rare. We present a case
      of a 42-year-old bedridden woman with mental and physical disabilities who had
      been misdiagnosed for a decade as having a bladder calculus. We removed the
      calculus nonsurgically and the analyzed the components. Results demonstrated the
      presence of a primary vaginal calculus. Vaginal calculi may occasionally occur in
      disabled women, but further investigation of the etiology of such calculi is
      required. 

PMID- 22872033
TI  - Postoperative management and restrictions for female pelvic surgery: a systematic
      review.
AB  - INTRODUCTION AND HYPOTHESIS: We sought to systematically review the literature
      regarding the effect of postoperative restrictions on clinical outcomes after
      pelvic surgery. METHODS: English-language articles were identified by a MEDLINE
      and Cochrane Central Register of Controlled Trials search from inception to July
      2010. We used key words describing various gynecologic surgical procedures and
      postoperative activities, including mobility, lifting, work, coitus, and
      exercise. Randomized and nonrandomized studies comparing interventions with
      outcomes of interest were included. RESULTS: The literature search yielded of
      3,491 articles; 115 full-text articles were reviewed, and 38 met eligibility
      criteria and are reported and analyzed here. Our analysis revealed that expedited
      discharge protocols and early postoperative feeding and catheter removal result
      in shorter hospital stay without negative health outcomes. However, there are
      limited data to guide many other aspects of postoperative care, particularly
      regarding exercise and resumption of sexual activity after surgery. CONCLUSIONS:
      There is good evidence to support early postoperative feeding and catheter
      removal after pelvic surgery. There are limited data to guide many other aspects
      of postoperative care.

PMID- 22872035
TI  - Transforming growth factor beta 1 gene expression during vaginal vs cutaneous
      surgical woundexpression during vaginal vs cutaneous surgical wound healing in
      the rabbit.
AB  - INTRODUCTION AND HYPOTHESIS: Reconstructive pelvic surgery outcome is closely
      related to the vaginal and pelvic wound healing processes. Transforming growth
      factor beta 1 (TGF-beta1) is a principal mediator of wound repair in dermal
      tissue. We sought to assess this factor's expression in vaginal and dermal
      surgical wound repair in the rabbit. METHODS: We excised bilateral 6-mm full
      thickness circular segments from the abdominal skin and vagina in 36 New Zealand
      White (NZW) nulliparous female rabbits. Animals were sacrificed before, on the
      day of, and 4, 7, 10, 14, 21, 28, and 35 days after tissue wounding, and their
      wounds were assessed for surface area and TGF-beta1 gene transcription by real
      time polymerase chain reaction (PCR). RESULTS: In both the abdominal skin and
      vagina, TGF-beta1 gene transcription increased immediately after tissue injury,
      reaching maximal levels on days 4-7, and decreased shortly thereafter, attaining
      minimal values on day 35. A significant correlation between TGF-beta1 expression
      and the wound's closure rate was found in both tissues. CONCLUSIONS: TGF-beta1
      gene transcription significantly correlates with the surgical vaginal and dermal
      wound closure rate, implying that this factor is involved in the process of wound
      repair in both tissues.

PMID- 22872041
TI  - Exploration of trade-offs between steady-state and dynamic properties in
      signaling cycles.
AB  - In the intracellular signaling networks that regulate important cell processes,
      the base pattern comprises the cycle of reversible phosphorylation of a protein,
      catalyzed by kinases and opposing phosphatases. Mathematical modeling and
      analysis have been used for gaining a better understanding of their functions and
      to capture the rules governing system behavior. Since biochemical parameters in
      signaling pathways are not easily accessible experimentally, it is necessary to
      explore possibilities for both steady-state and dynamic responses in these
      systems. While a number of studies have focused on analyzing these properties
      separately, it is necessary to take into account both of these responses
      simultaneously in order to be able to interpret a broader range of phenotypes.
      This paper investigates the trade-offs between optimal characteristics of both
      steady-state and dynamic responses. Following an inverse sensitivity analysis
      approach, we use systematic optimization methods to find the biochemical and
      biophysical parameters that simultaneously achieve optimal steady-state and
      dynamic performance. Remarkably, we find that even a single covalent modification
      cycle can simultaneously and robustly achieve high ultrasensitivity, high
      amplification and rapid signal transduction. We also find that the response rise
      and decay times can be modulated independently by varying the activating- and
      deactivating-enzyme-to-interconvertible-protein ratios.

PMID- 22872040
TI  - Effects of intracoronary delivery of allogenic bone marrow-derived stem cells
      expressing heme oxygenase-1 on myocardial reperfusion injury.
AB  - Heme oxygenase-1 (HO-1) decreases apoptosis, inflammation and oxidative stress.
      The aim of the study was to investigate the effects of intracoronary infusion of
      allogenic bone marrow cells (BMC) overexpressing HO-1 in the porcine model of
      myocardial infarction (MI). MI was produced by balloon occlusion of a coronary
      artery. BMC were transduced with adenoviruses encoding for HO-1 (HO-1 BMC) or GFP
      (GFP-BMC) genes. Prior to reperfusion animals received HO-1 BMC, control BMC
      (unmodified or GFP-BMC) or placebo. Left ventricular (LV) ejection fraction (EF),
      shortening fraction (SF), end-systolic and end-diastolic diameters (EDD, ESD)
      were assessed by echocardiography before, 30 minutes (min) and 14 days after
      reperfusion. BMC significantly improved LVEF and SF early (30 min) after
      reperfusion as well as after 14 days. Early after reperfusion HO-1 BMC were
      significantly more effective than control BMC, but after 14 days, there were no
      differences. There were no effect of cells on LV remodelling and diastolic
      function. Both HO-1 BMC and control BMC significantly reduced the infarct size
      vs. placebo (17.2 +/- 2.7 and 18.8 +/- 2.5, respectively, vs. 27.5 +/- 5.1, p=
      0.02) in histomorphometry. HO-1-positive donor BMC were detected in the infarct
      border area in pigs receiving HO-1-cells. No significant differences in
      expression of inflammatory genes (SDF-1, TNF-alpha, IL-6, miR21, miR29a and
      miR133a) in the myocardium were found. In conclusion, intracoronary delivery of
      allogeneic BMC immediately prior to reperfusion improved the LVEF and reduced the
      infarct size. HO-1 BMC were not superior to control cells after 14 days, however,
      produced faster recovery of LVEF. Transplanted cells survived in the peri-infarct
      zone.

PMID- 22872042
TI  - Information utilization in tactical decision making of middle management health
      managers.
AB  - Healthcare is an information-intensive field, as information is needed to make
      strategic, tactical, and operational decisions. The purpose of this study was to
      identify the tactical decisions that middle management healthcare managers make,
      the information that is available, and the necessary information that is missing
      using the cardiac care process as an example. Data were collected through focused
      interviews of nurses and physicians who work in middle management in a secondary
      healthcare field. The interviews were coded and analyzed using the thematic
      content analysis method. We identified two main categories of tactical decisions:
      those concerning the process of care and those concerning the resources for the
      care. We termed the categories "process decisions" and "resource decisions." The
      availability of information varied. Much of the necessary information was created
      and processed manually. Our results show that the collection, mining, and
      systematic use of information are difficult because of the existence of many
      types of information systems and their varying abilities to produce and report
      information. Finally, much of the important information is missing. In
      conclusion, the information management process in healthcare settings needs to be
      improved, and a new generation of information system is needed to support
      tactical decision making in middle management.

PMID- 22872043
TI  - Emotional competence and online game use in adolescents.
AB  - The purpose of this study was to explore the relations between emotional
      competence and online game use in adolescents. This study is a cross-sectional
      descriptive survey using a convenience sample. The participants were 2199
      adolescents in South Korea. Online game use and emotional competence including
      positive emotion, emotional expression, and emotional intelligence were measured.
      The study results indicated that emotional competence was negatively correlated
      with excessive online game use. All variables of emotional competence were
      significantly lower in high-risk users compared with general users. In addition,
      female adolescents were rated significantly higher in emotional competence among
      general users, but there were no significant gender differences among high-risk
      users. The results of our study imply that high-risk game users have lower levels
      of emotional intelligence than general users do. The results of this study
      suggest that emotion is an important factor to which practitioners in
      psychomedical fields and nursing should pay attention. Therefore, nurses in
      schools and communities should regularly screen the emotions of adolescents who
      habitually play online games and develop a program to enhance emotional
      competence associated with online games.

PMID- 22872044
TI  - An evaluation of a web-based diabetes education program designed to enhance self
      management among patients living with diabetes.
AB  - Diabetes is a global public health problem. Maintaining optimal glycemic control
      is critical for minimizing associated long-term complications and achieving
      better quality of life. Effective diabetes self-management education is one key
      component to enhance diabetes clients' self-management capabilities. The research
      team established a "Caring for Yourself-Managing Your Diabetes" Web site, which
      contained 35 video clips about diabetes management. The aim of this study was to
      evaluate user satisfaction with the Web-based diabetes self-management education
      program. A convenience sample of 100 diabetes clients (mean age, 61.5 [SD, 10.7]
      years) was invited to view one of the video clips via a laptop computer. A
      modified version of the Computer-Aided Learning Evaluation Questionnaire and the
      End-User Computing Satisfaction Questionnaire was used to evaluate participants'
      satisfaction with the program. The results indicate that participants were
      satisfied with the format, content, and accuracy of the Web-based diabetes
      education program. Some participants suggested adding different types of
      exercises that are specific to the needs of client groups and more explanation of
      diabetes medications. The results of this study support the use of computer
      assisted learning as a promising method for delivering diabetes self-management
      education, which is satisfactory to diabetes clients.

PMID- 22872045
TI  - Structural changes upon replacing carbonyl groups with thiocarbonyl groups in
      first row transition metal derivatives: new insights.
AB  - The chemistry of metal thiocarbonyls is much more limited than that of metal
      carbonyls because of the instability of CS as a synthetic reagent. In view of the
      many gaps remaining in experimentally realized metal thiocarbonyl chemistry,
      theoretical studies using density functional methods have been used to explore
      the possible future scope of metal thiocarbonyl chemistry. This paper reviews
      such theoretical studies on binuclear metal carbonyl derivatives of the types
      M(2)(CS)(2)(CO)(n) and Cp(2)M(2)(CS)(2)(CO)(n) (Cp = eta(5)-C(5)H(5); M = V
      through Ni) as well as the trinuclear and tetranuclear iron carbonyls
      Fe(3)(CS)(3)(CO)(n) (n = 9, 8, 7, 6) and Fe(4)(CS)(4)(CO)(n) (n = 12, 11, 10, 9).
      The substitution of one or two CO groups with CS groups to give less symmetrical
      structures leads to many more isomers. Structures in which a four-electron donor
      thiocarbonyl group uses its sulfur atom to bridge a metal-metal bond as a eta(2)
      MU-CS ligand are more favorable in binuclear metal thiocarbonyl chemistry than
      corresponding structures in metal carbonyl chemistry owing to the basicity of the
      sulfur atom. Six-electron donor thiocarbonyl groups bridging clusters of three or
      four iron atoms are also found in low-energy structures including a particularly
      favorable Fe(4)(CS)(4)(CO)(10) structure suggested as a possible target for
      future synthetic chemistry. In thiocarbonyl substitution products of simple
      binuclear metal carbonyls such as Fe(2)(CO)(9) [= Fe(2)(CO)(6)(MU-CO)(3)],
      Co(2)(CO)(8) [= Co(2)(CO)(6)(MU-CO)(2)], and Cp(2)Fe(2)(CO)(4) [=
      Cp(2)Fe(2)(CO)(2)(MU-CO)(2)], structures with bridging CS groups are invariably
      lower energy structures than isomeric structures with bridging CO groups.

PMID- 22872046
TI  - Organic functionalization of graphene in dispersions.
AB  - Graphene is considered a promising material for a range of new applications from
      flexible electronics to functional nanodevices, such as biosensors or intelligent
      coatings. Therefore researchers need to develop protocols for the mass production
      of graphene. One possible method is the exfoliation of graphite to form stable
      dispersions in organic solvents or even water. In addition, researchers need to
      find effective ways to control defects and locally induced chemical changes. We
      expect that traditional organic chemistry can provide solutions to many of these
      challenges. In this Account, we describe our efforts toward the production of
      stable dispersions of graphene in a variety of solvents at relatively high
      concentrations and summarize representative examples of the organic reactions
      that we have carried out using these stable dispersions.  The sonication
      procedures used to solubilize graphene can often damage these materials. To
      mitigate these effects, we developed a new methodology that uses mechanochemical
      activation by ball-milling to exfoliate graphite through interactions with
      melamine (2,4,6-triamine-1,3,5-triazine) under solid conditions. Alternatively,
      the addition of reducing agents during sonication leads to larger graphene layers
      in DMF. Interestingly, the treatment with ferrocene aldehyde, used as a radical
      trap, induces the formation of multiwalled carbon nanotubes. The resulting
      graphene sheets, stabilized by the interactions with the solvent, are suitable
      materials for performing organic reactions.  Relatively few organic reactions
      have been performed in stable dispersions of graphene, but organic
      functionalization of these materials offers the opportunity to tune their
      properties. In addition, thermal treatments can remove the appended organic
      moieties, restoring the intrinsic properties of pristine graphene. We describe a
      few examples of organic functionalization reactions of graphene, including 1,3
      dipolar cycloadditions, amide condensations, nitrene additions, and radical
      reactions. The design of novel protocols for further organic functionalization
      should increase our knowledge of the fundamental chemistry of graphene and spur
      the further development and application of these materials.

PMID- 22872047
TI  - Photoswitchable quantum dots by controlling the photoinduced electron transfers.
AB  - We report photoluminescence (PL) modulation of quantum dots (QDs) by photoinduced
      electron transfers from acridine-1,8-dione derivative surface ligands. Reversible
      PL switching upon many repeated cycles was demonstrated, as alternating on and
      off of the UV excitation for the surface ligand has successfully resulted in the
      QD PL modulation.

PMID- 22872048
TI  - Enhanced superconductivity by rare-earth metal doping in phenanthrene.
AB  - We successfully synthesized La- and Sm-doped phenanthrene powder samples and
      observed superconductivity in them at T(c) around 6 K. The T(c)s are 6.1 K for
      La(1) phenanthrene and 6.0 K for Sm(1) phenanthrene, which are enhanced by about
      1 and 0.5 K compared to those in A(3) phenanthrene (A = K and Rb) and in Ae(1.5)
      phenanthrene (Ae = Sr and Ba) superconductors, respectively. The superconductive
      shielding fractions for La(1) phenanthrene and Sm(1) phenanthrene are 46.1% and
      49.8% at 2 K, respectively. The small effect of doping with the magnetic ion
      Sm(3+) on T(c) and the positive pressure dependence coefficient of T(c) strongly
      suggest unconventional superconductivity in the doped phenanthrene
      superconductors. The charge transfer to organic molecules from dopants of La and
      Sm induces a redshift of 7 cm(-1) per electron for the mode at 1441 cm(-1) in the
      Raman spectra, which is almost the same as those observed in A(3) phenanthrene (A
      = K and Rb) and Ae(1.5) phenanthrene (Ae = Sr and Ba) superconductors.

PMID- 22872049
TI  - Immunogenicity of a divalent group A streptococcal vaccine.
AB  - We designed and recombined the polypeptide based on the M protein of group A
      streptococci (GAS)--the causative pathogen of rheumatic fever and rheumatic heart
      disease, which would be a divalent vaccine to prevent and defend the diseases in
      relation to the different GAS strains. A divalent vaccine comprising three
      different peptide epitopes of the antiphagocytic M protein of GAS--an
      aminoterminal specific sequences, respectively, from the M1 and M12 proteins and
      J14 peptide (ASREAKKQVEKALE) within the highly conserved C-terminal repeat region
      of the M1 and M12 proteins--was subcutaneously delivered to mice with the
      adjuvant. Furthermore, the antisera titers of mice inoculated with the divalent
      vaccine were assayed by ELISA, and then opsonization and percentage killing
      against two different GAS serotypes were completed. Our data demonstrated that
      antisera raised against the divalent vaccine containing amino acids and M-protein
      conserved C repeat region are able to kill several GAS strains isolated from the
      Guangzhou population. Therefore, the divalent vaccine can be used to prevent
      those diseases caused by GAS in an endemic area. We successfully construct the M
      protein-based divalent vaccine that can bring out a high-level antisera titer of
      mice vaccinated with it. So, the vaccine has the potential to be used to prevent
      diseases caused by GAS in our country.

PMID- 22872050
TI  - Detection of a novel recombinant strain of norovirus in an African-descendant
      community from the Amazon region of Brazil in 2008.
AB  - Noroviruses, a major cause of acute gastroenteritis outbreaks worldwide, are
      constantly evolving. This ability is reflected in the speed and efficiency with
      which these viruses spread and remain in the human population. The present study
      reports the detection of a novel recombination event among norovirus genotypes in
      Brazil in 2008. A strain detected in a stool sample from a child with norovirus
      associated gastroenteritis, residing in an African-descendant semi-closed
      community of Para State, was characterized as a novel intergenotype recombinant,
      GII.7/GII.20, as determined by partial sequencing and SimPlot analysis.

PMID- 22872051
TI  - Prosthesis oversizing in balloon-expandable transcatheter aortic valve
      implantation is associated with contained rupture of the aortic root.
AB  - BACKGROUND: To retrospectively investigate the potential cause of contained
      rupture of the aortic root in balloon-expandable transcatheter aortic valve
      implantation (TAVI) by means of pre- and postinterventional multislice computed
      tomography. METHODS AND RESULTS: Seventy-two patients (mean age 82+/-7 years,
      mean aortic valve area 0.69+/-0.19 cm(2)) underwent balloon-expandable TAVI using
      the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm,
      n=3). Aortic annulus dimensions were quantified by multislice computed tomography
      based cross-sectional area assessment and average diameter calculation (CAAD)
      before and after TAVI. Post-TAVI multislice computed tomography data sets were
      available in 65 patients; contained aortic root rupture was diagnosed in 3
      patients. Pre-TAVI CAAD was 23.1+/-1.8 mm; post-TAVI CAAD was 22.9+/-1.3 mm.
      Median relative change in CAAD pre- and post-TAVI was -0.5% (interquartile range,
      3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with
      contained rupture), relative increase >10% in 2 patients, both with contained
      rupture. Mean relative oversizing, calculated as the relative difference in
      diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis,
      was 9.8%+/-7.8%. Relative oversizing was significantly higher in patients with
      contained rupture compared with patients without contained rupture (24.6%+/-5.4%
      versus 9.1%+/-6.6%; P<0.001). Relative oversizing >=20% occurred in 6 patients (3
      with contained rupture). CONCLUSIONS: Contained rupture of the aortic root in
      balloon-expandable TAVI is associated with severe prosthesis oversizing.
      Multislice computed tomography-based assessment of aortic annulus dimension in
      conjunction with adapted sizing guidelines may reduce the incidence of severe
      oversizing.

PMID- 22872052
TI  - Long-term outcome of stents versus bypass surgery in diabetic and nondiabetic
      patients with multivessel or left main coronary artery disease: a pooled analysis
      of 5775 individual patient data.
AB  - BACKGROUND: Coronary artery bypass grafting and percutaneous coronary
      intervention (PCI) are alternative treatments for complex multivessel or left
      main disease. However, the relative treatment effects in diabetic and nondiabetic
      patients remain uncertain. METHODS AND RESULTS: We performed a pooled analysis of
      5775 patients from 3 clinical studies comparing PCI and coronary artery bypass
      grafting for multivessel or left main disease and compared adverse outcomes
      (death; a composite outcome of death, Q-wave myocardial infarction, or stroke;
      and repeat revascularization) according to the diabetic status. Over a median
      follow-up of 5.5 years, risk-adjusted mortality after PCI relative to coronary
      artery bypass grafting was not different in diabetic (hazard ratio [HR], 1.15;
      95% CI, 0.88-1.51) and nondiabetic (HR, 1.15; 95% CI, 0.88-1.50) patients. The
      adjusted risks of the composite outcome of death, Q-wave myocardial infarction,
      or stroke were also not different in diabetic (HR, 1.00; 95% CI, 0.79-1.26) and
      nondiabetic (HR, 0.99; 95% CI, 0.78-1.26) patients. However, PCI was
      significantly associated with higher risk of repeat revascularization both in
      diabetic (HR, 3.56; 95% CI, 2.62-4.83) and in nondiabetic (HR, 3.55; 95% CI, 2.61
      4.83) patients. Significant interactions were absent between diabetic status and
      revascularization strategies for death (P=0.27), composite outcome of death, Q
      wave myocardial infarction, or stroke (P=0.97), and repeat revascularization
      (P=0.08). CONCLUSIONS: For multivessel or left main disease, the long-term risks
      of mortality and composite serious outcomes were not different between PCI and
      coronary artery bypass grafting in diabetic and nondiabetic patients, but PCI was
      associated with higher risk of repeat revascularization. These relative treatment
      effects were not modified by diabetic status. These results are hypothesis
      generating and should be addressed in a randomized trial.

PMID- 22872053
TI  - Percutaneous coronary intervention versus optimal medical therapy in stable
      coronary artery disease: a systematic review and meta-analysis of randomized
      clinical trials.
AB  - BACKGROUND: The role of percutaneous coronary intervention (PCI) in the
      management of stable coronary artery disease remains controversial. Given
      advancements in medical therapies and stent technology over the last decade, we
      sought to evaluate whether PCI, when added to medical therapy, improves outcomes
      when compared with medical therapy alone. METHODS AND RESULTS: We performed a
      systematic review and meta-analysis, searching PubMed, EMBASE, and CENTRAL
      databases, until January 2012, for randomized clinical trials comparing
      revascularization with PCI to optimal medical therapy (OMT) in patients with
      stable coronary artery disease. The primary outcome was all-cause mortality, and
      secondary outcomes included cardiovascular death, nonfatal myocardial infarction,
      subsequent revascularization, and freedom from angina. Primary analyses were
      based on longest available follow-up with secondary analyses stratified by trial
      duration, with short-term (<=1 year), intermediate (1-5 years), and long-term
      (>=5 years) time points. We identified 12 randomized clinical trials enrolling
      7182 participants who fulfilled our inclusion criteria. For the primary analyses,
      when compared with OMT, PCI was associated with no significant improvement in
      mortality (risk ratio [RR], 0.85; 95% CI, 0.71-1.01), cardiac death (RR, 0.71;
      95% CI, 0.47-1.06), nonfatal myocardial infarction (RR, 0.93; 95% CI, 0.70-1.24),
      or repeat revascularization (RR, 0.93; 95% CI, 0.76-1.14), with consistent
      results over all follow-up time points. Sensitivity analysis restricted to
      studies in which there was >50% stent use showed attenuation in the effect size
      for all-cause mortality (RR, 0.93; 95% CI, 0.78-1.11) with PCI. However, for
      freedom from angina, there was a significant improved outcome with PCI, as
      compared with the OMT group (RR, 1.20; 95% CI, 1.06-1.37), evident at all of the
      follow-up time points. CONCLUSIONS: In this most rigorous and comprehensive
      analysis in patients with stable coronary artery disease, PCI, as compared with
      OMT, did not reduce the risk of mortality, cardiovascular death, nonfatal
      myocardial infarction, or revascularization. PCI, however, provided a greater
      angina relief compared with OMT alone, larger studies with sufficient power are
      required to prove this conclusively.

PMID- 22872054
TI  - Transport time and care processes for patients transferred with ST-segment
      elevation myocardial infarction: the reperfusion in acute myocardial infarction
      in Carolina emergency rooms experience.
AB  - BACKGROUND: For patients with ST-segment elevation myocardial infarction
      transferred for primary percutaneous coronary intervention, guidelines have
      called for device activation within 90 minutes of initial presentation. Fewer
      than 20% of transferred patients are treated in such a timely fashion. We examine
      the association between transfer drive times and door-to-device (D2D) times in a
      network of North Carolina hospitals. We compare the feasibility of timely
      percutaneous coronary intervention using ground versus air transfer. METHODS AND
      RESULTS: We perform a retrospective analysis of the relationship between transfer
      drive times and D2D times in a 119-hospital ST-segment-elevation myocardial
      infarction statewide network. Between July 2008 and December 2009, 1537 ST
      segment-elevation myocardial infarction patients underwent interhospital transfer
      for reperfusion via primary percutaneous coronary intervention. For ground
      transfers, median D2D time was 93 minutes for drive times <=30 minutes, 117
      minutes for drive times of 31 to 45 minutes, and 121 minutes for drive times >45
      minutes. For air transfers, median D2D time was 125 minutes for drive times of 31
      to 45 minutes and 138 minutes for drive times >45 minutes. Helicopter transport
      was associated with longer door-in door-out times and, ultimately, was associated
      with median D2D times that exceeded guideline recommendations, no matter the
      transfer drive time category. CONCLUSIONS: In a well-developed ST-segment
      elevation myocardial infarction system, D2D times within 90 to 120 minutes appear
      most feasible for hospitals within 30-minute transfer drive time. Helicopter
      transport did not offer D2D time advantages for transferred STEMI patients. This
      finding appears to be attributable to comparably longer door-in door-out times
      for air transfers.

PMID- 22872055
TI  - Gene transfer into older chicken embryos by ex ovo electroporation.
AB  - The chicken embryo provides an excellent model system for studying gene function
      and regulation during embryonic development. In ovo electroporation is a powerful
      method to over-express exogenous genes or down-regulate endogenous genes in vivo
      in chicken embryos(1). Different structures such as DNA plasmids encoding genes(2
      4), small interfering RNA (siRNA) plasmids(5), small synthetic RNA oligos(6), and
      morpholino antisense oligonucleotides(7) can be easily transfected into chicken
      embryos by electroporation. However, the application of in ovo electroporation is
      limited to embryos at early incubation stages (younger than stage HH20--according
      to Hamburg and Hamilton)(8) and there are some disadvantages for its application
      in embryos at later stages (older than stage HH22--approximately 3.5 days of
      development). For example, the vitelline membrane at later stages is usually
      stuck to the shall membrane and opening a window in the shell causes rupture of
      the vessels, resulting in death of the embryos; older embryos are covered by
      vitelline and allantoic vessels, where it is difficult to access and manipulate
      the embryos; older embryos move vigorously and is difficult to control the
      orientation through a relatively small window in the shell. In this protocol we
      demonstrate an ex ovo electroporation method for gene transfer into chicken
      embryos at late stages (older than stage HH22). For ex ovo electroporation,
      embryos are cultured in Petri dishes(9) and the vitelline and allantoic vessels
      are widely spread. Under these conditions, the older chicken embryos are easily
      accessed and manipulated. Therefore, this method overcomes the disadvantages of
      in ovo electroporation applied to the older chicken embryos. Using this method,
      plasmids can be easily transfected into different parts of the older chicken
      embryos(10-12).

PMID- 22872056
TI  - Environmentally relevant mixtures in cumulative assessments: an acute study of
      toxicokinetics and effects on motor activity in rats exposed to a mixture of
      pyrethroids.
AB  - Due to extensive use, human exposure to multiple pyrethroid insecticides occurs
      frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity
      and that pyrethroids should be considered cumulatively to model risk. The
      objective of this work was to use a pyrethroid mixture that reflects human
      exposure to common pyrethroids to develop comparative toxicokinetic profiles in
      rats, and then model the relationship between brain concentration and motor
      activity. Data from a national survey of child care centers were used to make a
      mixture reflecting proportions of the most prevalent pyrethroids: permethrin,
      cypermethrin, beta-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was
      administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult
      male rats. At intervals from 1 to 24h, motor activity was assessed and the
      animals were sacrificed. Pyrethroid concentrations were measured in the blood,
      liver, fat, and brain. After controlling for dose, there were no differences in
      any tissue concentrations, except blood at the initial time point. Elimination
      half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of
      all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time
      point were proportional to their relative doses. Decreases in motor activity
      indicated dose additivity, and the relationship between pyrethroid brain
      concentration and motor activity was described by a four-parameter sigmoidal
      E(max) model. This study links environmental data with toxicokinetic and
      neurobehavioral assays to support cumulative risk assessments of pyrethroid
      pesticides. The results support the additive model of pyrethroid effect on motor
      activity and suggest that variation in the neurotoxicity of individual
      pyrethroids is related to toxicodynamic rather than toxicokinetic differences.

PMID- 22872057
TI  - Mutagenesis by an antisense oligonucleotide and its degradation product.
AB  - The European Medicines Agency has expressed concern regarding (1) the potential
      for antisense oligonucleotide (ASO) therapeutics to induce sequence-specific
      mutation at genomic DNA and (2) the capability of ASO degradation products
      (nucleotide analogues) to incorporate into newly synthesized genomic DNA via DNA
      polymerase and cause mutation if base pairing occurs with reduced fidelity.
      Treating human lymphoblastoid cells with a biologically active antisense molecule
      induced sequence-specific mutation within genomic DNA over fourfold, in a system
      where RAD51 protein expression was induced. This finding has implications for ASO
      therapeutics with individuals with an induced DNA damage response, such as cancer
      patients. Furthermore, a phosphorothioate nucleotide analogue potently induced
      mutation at genomic DNA two orders of magnitude above control. This study shows
      that a biologically active ASO molecule can induce heritable sequence
      alterations, and if degraded, its respective analogue may incorporate into
      genomic DNA with mutagenic consequences.

PMID- 22872058
TI  - A performance evaluation of three drug-induced liver injury biomarkers in the
      rat: alpha-glutathione S-transferase, arginase 1, and 4-hydroxyphenyl-pyruvate
      dioxygenase.
AB  - Alanine aminotransferase (ALT) activity is the most frequently relied upon
      reference standard for monitoring liver injury in humans and nonclinical species.
      However, limitations of ALT include a lack of specificity for diagnosing liver
      injury (e.g., present in muscle and the gastrointestinal tract), its inability to
      monitor certain types of hepatic injury (e.g., biliary injury), and ambiguity
      with respect to interpretation of modest or transient elevations (< 3* upper
      limit of normal). As an initial step to both understand and qualify additional
      biomarkers of hepatotoxicity that may add value to ALT, three novel candidates
      have been evaluated in 34 acute toxicity rat studies: (1) alpha-glutathione S
      transferase (GSTA), (2) arginase 1 (ARG1), and (3) 4-hydroxyphenylpyruvate
      dioxygenase (HPD). The performance of each biomarker was assessed for its
      diagnostic ability to accurately detect hepatocellular injury (i.e., microscopic
      histopathology), singularly or in combination with ALT. All three biomarkers,
      either alone or in combination with ALT, improved specificity when compared with
      ALT alone. Hepatocellular necrosis and/or degeneration were detected by all three
      biomarkers in the majority of animals. ARG1 and HPD were also sensitive in
      detecting single-cell necrosis in the absence of more extensive hepatocellular
      necrosis/degeneration. ARG1 showed the best sensitivity for detecting biliary
      injury with or without ALT. All the biomarkers were able to detect biliary injury
      with single-cell necrosis. Taken together, these novel liver toxicity biomarkers,
      GSTA, ARG1, and HPD, add value (both enhanced specificity and sensitivity) to the
      measurement of ALT alone for monitoring drug-induced liver injury in rat.

PMID- 22872059
TI  - Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein
      expression and neurodegeneration in adult hippocampus.
AB  - The cyanobacterial toxin beta-N-methylamino-L-alanine (BMAA) has been proposed to
      contribute to neurodegenerative disease. We have previously reported a selective
      uptake of BMAA in the mouse neonatal hippocampus and that exposure during the
      neonatal period causes learning and memory impairments in adult rats. The aim of
      this study was to characterize effects in the brain of 6-month-old rats treated
      neonatally (postnatal days 9-10) with the glutamatergic BMAA. Protein changes
      were examined using the novel technique Matrix-Assisted Laser Desorption
      Ionization (MALDI) imaging mass spectrometry (IMS) for direct imaging of proteins
      in brain cryosections, and histological changes were examined using
      immunohistochemistry and histopathology. The results showed long-term changes
      including a decreased expression of proteins involved in energy metabolism and
      intracellular signaling in the adult hippocampus at a dose (150 mg/kg) that gave
      no histopathological lesions in this brain region. Developmental exposure to a
      higher dose (460 mg/kg) also induced changes in the expression of S100beta,
      histones, calcium- and calmodulin-binding proteins, and guanine nucleotide
      binding proteins. At this dose, severe lesions in the adult hippocampus including
      neuronal degeneration, cell loss, calcium deposits, and astrogliosis were
      evident. The data demonstrate subtle, sometimes dose-dependent, but permanent
      effects of a lower neonatal dose of BMAA in the adult hippocampus suggesting that
      BMAA could potentially disturb many processes during the development. The
      detection of BMAA in seafood stresses the importance of evaluating the magnitude
      of human exposure to this neurotoxin.

PMID- 22872060
TI  - Ethanol enhances tumor angiogenesis in vitro induced by low-dose arsenic in colon
      cancer cells through hypoxia-inducible factor 1 alpha pathway.
AB  - Health effects due to environmental exposure to arsenic are a major global health
      concern. Arsenic has been known to induce carcinogenesis and enhance tumor
      development via complex and unclear mechanism. Ethanol is also a well-established
      risk factor for many malignancies. However, little is known about the effects of
      coexposure to arsenic and ethanol in tumor development. In this study, we
      investigate the signaling and angiogenic effect of coexposure of arsenic and
      ethanol on different colon cancer cell lines. Results show that ethanol markedly
      enhanced arsenic-induced tumor angiogenesis in vitro. These responses are related
      to intracellular reactive oxygen species (ROS) generation, NADPH oxidase
      activation, and upregulation of PI3K/Akt and hypoxia-inducible factor 1 alpha
      (HIF-1alpha) signaling. We have also found that ethanol increases the arsenic
      induced expression and secretion of angiogenic signaling molecules such as
      vascular endothelial growth factor, which further confirmed the above
      observation. Antioxidant enzymes inhibited arsenic/ethanol-induced tumor
      angiogenesis, demonstrating that the responsive signaling pathways of coexposure
      to arsenic and ethanol are related to ROS generation. We conclude that ethanol is
      able to enhance arsenic-induced tumor angiogenesis in colorectal cancer cells via
      the HIF-1alpha pathway. These results indicate that alcohol consumption should be
      taken into consideration in the investigation of arsenic-induced carcinogenesis
      in arsenic-exposed populations.

PMID- 22872061
TI  - Cost-minimisation and cost-effectiveness analysis comparing transoral CO2 laser
      cordectomy, laryngofissure cordectomy and radiotherapy for the treatment of T1-2,
      N0, M0 glottic carcinoma.
AB  - The financial costs of laryngeal cancer treatment are a notable burden on
      healthcare budgets. In this study, we assess whether CO2 laser surgery is cheaper
      than radiotherapy or laryngofissure and cordectomy in the treatment of T1-2, N0,
      M0 glottic squamous cell carcinoma. 56 patients with a mean age of 65.88 years
      (SD = 10.04), 53 men and 3 women, with T1-2, N0, M0 glottic squamous cell
      carcinoma were retrospectively analysed. We conducted a comparative analysis of
      costs associated with three treatments: carbon dioxide laser cordectomy (n = 21),
      radiotherapy (n = 20), and laryngofissure cordectomy (n = 15). Complications of
      the radiotherapy and surgical treatments, need for tracheotomy and its
      permanence, length of hospital stay, occupation and ability to work and economic
      costs of treatments were recorded. Cost-minimisation and cost-effectiveness
      analysis were obtained. The cost of transoral laser cordectomy (2,289.79 euro) is
      statistically significantly lower than that of radiotherapy (4,804.72 euro) or
      laryngofissure cordectomy (13,229.75 euro) (p < 0.001). Transoral carbon dioxide
      laser surgery is the best option in terms of cost-effectiveness for the treatment
      of T1-2, N0, M0 glottic cancer.

PMID- 22872062
TI  - Letter regarding "Characteristics and management of intractable neck involvement
      in tularemia".

PMID- 22872063
TI  - Eye proprioception may provide real time eye position information.
AB  - Because of the frequency of eye movements, online knowledge of eye position is
      crucial for the accurate spatial perception and behavioral navigation. Both the
      internal monitoring signal (corollary discharge) of eye movements and the eye
      proprioception signal are thought to contribute to the localization of the eye
      position in the orbit. However, the functional role of these two eye position
      signals in spatial cognition has been disputed for more than a century. The
      predominant view proposes that the online analysis of eye position is exclusively
      provided by the corollary discharge signal, while the eye proprioception signal
      only plays a role in the long-term calibration of the oculomotor system. However,
      increasing evidence from recent behavioral and physiological studies suggests
      that the eye proprioception signal may play a role in the online monitoring of
      eye position. The purpose of this review is to discuss the feasibility and
      possible function of the eye proprioceptive signal for online monitoring of eye
      position.

PMID- 22872065
TI  - Cobalt analogues of Roussin's red salt esters: a density functional study.
AB  - Density functional theory calculations on the Co(2)(NO)(4)(SR)(2) compounds (R =
      CH(3), CF(3) and C(4)H(9)) predict butterfly and open isomeric structures with
      and without a direct Co-Co bond. The open Co(2)(NO)(4)(SR)(2) structures are
      favored over the butterfly isomers, in terms of relative energy. Furthermore the
      open structures are predicted to have approximately twice as large HOMO-LUMO gaps
      than the butterfly Co(2)(NO)(4)(SR)(2) isomers. For the related
      Co(2)(CO)(6)(SR)(2) species, competing open and butterfly structures with similar
      HOMO-LUMO gaps were predicted. This could explain why the Co(2)(NO)(4)(MU-SR)(2)
      compounds have already been synthesized and why no genuine Co(2)(CO)(6)(SR)(2)
      derivatives have yet been reported.

PMID- 22872064
TI  - Hippocampal neuron loss is correlated with cognitive deficits in SAMP8 mice.
AB  - The objective of this study is to examine whether neuron loss occurs in SAMP8 and
      whether neuron loss is correlated with cognitive deficits of these mice. Neuronal
      loss is considered as one of the most important pathological hallmarks of
      Alzheimer disease (AD). In addition to the early-onset, irreversible, severe
      deficits of learning and memory, SAMP8 mice show spontaneous age-related
      neurodegenerative changes and other characteristics seen in AD patients, such as
      amyloid plaques and neurofibrillary tangles. However, it is still unknown whether
      neuron loss occurs in SAMP8 and whether neuron loss is correlated with cognitive
      deficits of these mice. We employed 8-month-old SAMP8 and SAMR1 mice to
      investigate the cognitive function and neuron numbers. The behaviors were
      examined by the grading score of senescence and Morris water maze (MWM) test, the
      neuron number in hippocampus was estimated by the optical fractionator technique.
      The grading score of senescence and MWM test demonstrated that SAMP8 exhibited
      notable age-related changes in appearance and cognitive function. Moreover,
      severe hippocampal neuron loss was found in SAMP8 as determined by the optical
      fractionator stereological method. Compared to SAMR1, the neuron number of CA1,
      CA3 and DG in SAMP8 was reduced by 15.6, 19.8 and 20.2 %, respectively, and the
      neuron loss in hippocampus was associated with cognitive deficits. Collectively,
      these results suggest that hippocampal neuronal loss is well correlated with
      learning and memory deficits in SAMP8 and SAMP8 represents an important mouse
      model for AD.

PMID- 22872066
TI  - Self-reported nocturnal sleep duration is associated with next-day resting state
      functional connectivity.
AB  - Sleep deprivation affects cerebral metabolism and reduces the functional
      connectivity among various regions of the brain, potentially explaining some of
      the associated mood and emotional changes often observed. Prior neuroimaging
      studies have only examined the effects of sleep deprivation or partial sleep
      restriction on functional connectivity, but none have studied how such
      connectivity is associated with normal variations in self-reported sleep duration
      the night before the scan. We examined the relationship between sleep duration
      and resting state functional connectivity among healthy volunteers who slept at
      home according to their own schedules. Thirty-nine healthy individuals aged 18-45
      (21 females) completed a questionnaire asking about their recent sleep habits and
      entries in their sleep diary for the previous night, followed by resting state
      functional MRI at 3 T. Participants reported sleeping between 5.0 and 8.5 h the
      night before the scan (M=7.0, SD=0.9). Seed regions were placed in the medial
      prefrontal cortex and posterior cingulate cortex nodes of the default mode
      network, regions previously implicated in sleep deprivation. Longer self-reported
      sleep duration was associated with significantly enhanced functional connectivity
      between the medial prefrontal cortex and posterior cingulate, as well as greater
      anticorrelations with parietal, occipital, and lateral prefrontal regions.
      Findings suggest that even normal variations in sleep duration measured by self
      report are related to the strength of functional connectivity within select nodes
      of the default mode network and its anticorrelated network.

PMID- 22872067
TI  - Predicting mortality for paediatric inpatients where malaria is uncommon.
AB  - OBJECTIVE: As the proportion of children living low malaria transmission areas in
      sub-Saharan Africa increases, approaches for identifying non-malarial severe
      illness need to be evaluated to improve child outcomes. DESIGN: As a prospective
      cohort study, we identified febrile paediatric inpatients, recorded data using
      Integrated Management of Childhood Illness (IMCI) criteria, and collected
      diagnostic specimens. SETTING: Tertiary referral centre, northern Tanzania.
      RESULTS: Of 466 participants with known outcome, median age was 1.4 years (range
      2 months-13.0 years), 200 (42.9%) were female, 11 (2.4%) had malaria and 34
      (7.3%) died. Inpatient death was associated with: Capillary refill >3 s (OR 9.0,
      95% CI 3.0 to 26.7), inability to breastfeed or drink (OR 8.9, 95% CI 4.0 to
      19.6), stiff neck (OR 7.0, 95% CI 2.8 to 17.6), lethargy (OR 5.2, 95% CI 2.5 to
      10.6), skin pinch >2 s (OR 4.8, 95% CI 1.9 to 12.3), respiratory difficulty (OR
      4.0, 95% CI 1.9 to 8.2), generalised lymphadenopathy (OR 3.6, 95% CI 1.6 to 8.3)
      and oral candidiasis (OR 3.4, 95% CI 1.4 to 8.3). BCS <5 (OR 27.2, p<0.001) and
      severe wasting (OR 6.9, p<0.001) were independently associated with inpatient
      death. CONCLUSIONS: In a low malaria transmission setting, IMCI criteria
      performed well for predicting inpatient death from non-malarial illness.
      Laboratory results were not as useful in predicting death, underscoring the
      importance of clinical examination in assessing prognosis. Healthcare workers
      should consider local malaria epidemiology as malaria over-diagnosis in children
      may delay potentially life-saving interventions in areas where malaria is
      uncommon.

PMID- 22872068
TI  - Evaluation of urinary N-telopeptide of type I collagen measurements in the
      management of osteoporosis in clinical practice.
AB  - We measured urinary N-telopeptide of type I collagen (U-NTX) to monitor response
      to bisphosphonates for osteoporosis. Decrease in U-NTX was associated with
      increase in spine bone density. A lesser response in U-NTX was more likely in
      those with secondary osteoporosis or with poor compliance. U-NTX may be a useful
      early indicator of treatment non-compliance or secondary osteoporosis.
      INTRODUCTION: This study aims to determine the utility of the bone resorption
      marker, U-NTX, in the clinical setting, to monitor the response to bisphosphonate
      therapy (alendronate and risedronate) for osteoporosis. METHODS: A retrospective
      evaluation of data collected as part of the bone turnover marker monitoring
      service in the Metabolic Bone Centre, Sheffield, UK. Treatment compliance,
      underlying causes of osteoporosis, change in U-NTX/creatinine (Cr) at 4 months
      and change in spine and hip bone mineral density (BMD) by dual-energy X-ray
      absorptiometry were recorded. Treatment response was defined as either a change
      in U-NTX/Cr greater than a pre-defined least significant change (LSC) of 54 % or
      to within the lower half of a pre-defined pre-menopausal reference interval (<=
      30 nM BCE/mmol Cr). RESULTS: A greater decrease in U-NTX/Cr at 4 months was
      associated with a greater increase in spine BMD at 18 months (r = -0.33; P <
      0.0001, Pearson's correlation). The mean U-NTX/Cr at 4 months was higher in
      patients with secondary osteoporosis compared with those with primary
      osteoporosis (P < 0.01, ANOVA). A lesser response in U-NTX/Cr increased the
      likelihood of secondary osteoporosis or poor treatment compliance (P = 0.04,
      Fisher's exact test). A lack of response in U-NTX/Cr to within the lower half of
      the reference interval was a better indicator of secondary osteoporosis and
      treatment non-compliance than a change in U-NTX/Cr greater than LSC. CONCLUSIONS:
      Treatment monitoring using U-NTX/Cr has a place in clinical practice for the
      early identification of non-compliance or presence of secondary osteoporosis.

PMID- 22872069
TI  - The contributions of First Nations ethnicity, income, and delays in surgery on
      mortality post-fracture: a population-based analysis.
AB  - We examined the independent contributions of First Nations ethnicity and lower
      income to post-fracture mortality. A similar relative increase in mortality
      associated with fracture appears to translate into a larger absolute increase in
      post-fracture mortality for First Nations compared to non-First Nations peoples.
      Lower income also predicted increased mortality post-fracture. INTRODUCTION:
      First Nations peoples have a greater risk of mortality than non-First Nations
      peoples. We examined the independent contributions of First Nations ethnicity and
      income to mortality post-fracture, and associations with time to surgery post-hip
      fracture. METHODS: Non-traumatic fracture cases and fracture-free controls were
      identified from population-based administrative data repositories for Manitoba,
      Canada (aged>=50 years). Populations were retrospectively matched for sex, age
      (within 5 years), First Nations ethnicity, and number of comorbidities.
      Differences in mortality post-fracture of hip, wrist, or spine, 1996-2004
      (population 1, n=63,081), and the hip, 1987-2002(Population 2, n=41,211) were
      examined using Cox proportional hazards regression to model time to death. For
      hip fracture, logistic regression analyses were used to model the probability of
      death within 30 days and 1 year. RESULTS: Population 1: First Nations ethnicity
      was associated with an increased mortality risk of 30-53% for each fracture type.
      Lower income was associated with an increased mortality risk of 18-26%.
      Population 2: lower income predicted mortality overall (odds ratio (OR) 1.15, 95%
      confidence interval (CI) 1.07-1.23) and for hip fracture cases (OR 1.18, 95%CI
      1.05-1.32), as did older age, male sex, diabetes, and >5 comorbidities (all
      p<=0.01). Higher mortality was associated with pertrochanteric fracture (OR 1.14,
      95% CI 1.03-1.27), or surgery delay of 2-3 days (OR 1.34, 95% CI 1.18-1.52) or
      >=4 days (OR 2.35, 95% CI 2.07-2.67). CONCLUSION: A larger absolute increase in
      mortality post-fracture was observed for First Nations compared to non-First
      Nations peoples. Lower income and surgery delay>2 days predicted mortality post
      fracture. These data have implications regarding prioritization of healthcare to
      ensure targeted, timely care for First Nations peoples and/or individuals with
      lower income.

PMID- 22872070
TI  - Two-year cost comparison of vertebroplasty and kyphoplasty for the treatment of
      vertebral compression fractures: are initial surgical costs misleading?
AB  - The costs for treating kypho- and vertebroplasty patients were evaluated at up to
      2 years postsurgery. There were no significant differences in adjusted costs in
      the first 9 months postsurgery, but kyphoplasty patients were associated with
      significantly lower adjusted treatment costs by 6.8-7.9% in the remaining periods
      through 2 years postsurgery. INTRODUCTION: Vertebral augmentation has been shown
      to be safe and effective for treating vertebral compression fractures.
      Comparative cost studies of initial treatment costs for kypho- and vertebroplasty
      have been mixed. The purpose of our study was to compare the costs for treating
      kypho- and vertebroplasty patients at up to 2 years postsurgery. METHODS:
      Vertebroplasty and kyphoplasty patients diagnosed with pathologic or closed
      lumbar/thoracic vertebral fractures were identified from the 5% sample of the
      Medicare dataset (2006-2009). The final study cohort with at least 2 years follow
      up comprised of 1,609 vertebroplasty and 2,878 kyphoplasty patients. The
      cumulative treatment costs (adjusted to June 2011 US$) were determined from the
      payer perspective. Differences in costs and length of stay were assessed by
      generalized linear mixed model regression, adjusting for covariates. RESULTS: The
      average adjusted costs for vertebroplasty patients within the first quarter and
      the first 2 years postsurgery were $14,585 [95% confidence interval (CI), $14,109
      15,078] and $44,496 (95% CI, $42,763-46,299), respectively. The corresponding
      average adjusted costs for kyphoplasty patients were $15,117 (95% CI, $14,752
      15,491) and $41,339 (95% CI, $40,154-42,560). There were no significant
      differences in adjusted costs in the first 9 months postsurgery, but kyphoplasty
      patients were associated with significantly lower adjusted treatment costs by 6.8
      7.9% in the remaining periods through 2 years postsurgery. CONCLUSION: Our
      present study addresses some of the limitations in previous comparative cost
      studies of vertebroplasty and kyphoplasty. The higher adjusted costs for
      vertebroplasty patients than kyphoplasty patients by 1 year following the surgery
      reflect greater utilization of medical resources.

PMID- 22872072
TI  - [Jean-Martin Charcot: on the anniversary of his death on 16th August].

PMID- 22872071
TI  - Severity of aortic calcification is positively associated with vertebral fracture
      in older men--a densitometry study in the STRAMBO cohort.
AB  - In older men, severe abdominal aortic calcification and vertebral fracture (both
      assessed using dual-energy X-ray absorptiometry) were positively associated after
      adjustment for confounders including bone mineral density. INTRODUCTION:
      Abdominal aortic calcification (AAC) is associated with higher fracture risk,
      independently of low bone mineral density (BMD). Dual-energy X-ray absorptiometry
      (DXA) can be used to assess both vertebral fracture and AAC and requires less
      time, cost, and radiation exposure. METHODS: We conducted a cross-sectional study
      of the association between AAC and prevalent vertebral fractures in 901 men>=50
      years old. We used DXA (vertebral fracture assessment) to evaluate BMD, vertebral
      fracture, and AAC. RESULTS: Prevalence of vertebral fracture was 11%. Median AAC
      score was 1 and 12% of men had AAC score>6. After adjustment for age, weight,
      femoral neck BMD, smoking, ischemic heart disease, diabetes, and hypertension,
      AAC score>6 (vs <=6) was associated with 2.5 (95% CI, 1.4-4.5) higher odds of
      vertebral fracture. Odds of vertebral fracture for AAC score>6 increased with
      vertebral fracture severity (grade 1, OR=1.8; grade 2, OR=2.4; grade 3, OR=4.4;
      trend p<0.01) and with the number of vertebral fractures (1 fracture, OR=2.0, >1
      fracture, OR=3.5). Prevalence of vertebral fracture was twice as high in men
      having both a T-score<-2.0 and an AAC score>6 compared with men having only one
      of these characteristics. CONCLUSIONS: Men with greater severity AAC had greater
      severity and greater number of vertebral fractures, independently of BMD and co
      morbidities. DXA can be used to assess vertebral fracture and AAC. It can provide
      a rapid, safe, and less expensive alternative to radiography. DXA may be an
      important clinical tool to identify men at high risk of adverse outcomes from
      osteoporosis and cardiovascular disease.

PMID- 22872073
TI  - CuCl-K2CO3-catalyzed highly selective borylcupration of internal alkynes--ligand
      effect.
AB  - An efficient and practical copper-catalyzed highly regio- and stereoselective
      borylcupration of internal alkynes with bis(pinacolato)diboron using a catalytic
      amount of K(2)CO(3) as base producing Z-alkenylboron compounds has been
      demonstrated by applying the ligand effect: commercially available electron-rich
      tris(p-methoxyphenyl) phosphine ensures a smooth and efficient reaction.
      Functionalized alkynes, such as propargylic alcohols and derivatives as well as N
      propargyl tosylamide, may also be used with excellent selectivity.

PMID- 22872074
TI  - Hepatocellular carcinoma:  initial tumour response after short-term and long
      interval chemoembolization with drug-eluting beads using modified RECIST.
AB  - OBJECTIVE: The aim of this study was to evaluate the initial tumour response
      after one, respectively, two transarterial chemoembolizations (TACE) with drug
      eluting (DC) beads in patients with hepatocellular carcinoma (HCC). METHODS: A
      total of 26 patients with clinically approved HCC underwent one or two TACE with
      DC Beads within 6 weeks and were evaluated after 12 weeks by MRI or computed
      tomography on the basis of the modified Response Evaluation Criteria in the Solid
      Tumours guidelines for HCC. For improved comparability of both groups, 16
      patients were matched in terms of Child-Pugh classification, Barcelona
      classification of liver cancer, age and sex. RESULTS: The overall tumour response
      showed progressive disease in 11% and an objective response in 89% for the double
      TACE group compared with progressive disease in 29.5%, objective response in
      34.5% and stable disease in 35% for the single TACE group. In the matched
      population, absolute tumour shrinkage was 61.1 +/- 28.3% for the double TACE
      group and 14.1 +/- 38.5% for the single TACE group (P<0.05). CONCLUSION: This
      retrospective study shows significantly higher tumour shrinkage in patients who
      underwent two TACE within 6 weeks compared with patients who underwent a single
      intervention in terms of the initial response rate after 12 weeks. It emphasizes
      the use of matched populations for the evaluation of tumour response in HCC after
      TACE.

PMID- 22872075
TI  - Influences on the amount of intraperitoneal haemorrhage after blunt liver injury:
      a retrospective autopsy study.
AB  - OBJECTIVE: The amount of intraperitoneal blood loss due to traumatic liver injury
      is rarely addressed in correlation with concomitant injuries or pre-existing
      liver disease. METHODS: We carried out a retrospective review of autopsy reports
      from 1995 until 2007 at the Institute of Forensic Medicine (Bern, Switzerland),
      and evaluated 126 cases of blunt liver trauma for the amount of blood in the
      abdominal cavity, severity of liver injury, pre-existing liver disease and
      concomitant injuries. RESULTS: Grades IV and V liver injuries (American
      Association for the Surgery of Trauma classification) showed greater blood loss
      than grades I and II liver injuries. Grade III liver injuries showed no
      significant difference in the amount of intraperitoneal blood compared with
      grades IV and V liver injuries and 53 cases of liver injuries (42%) did not bleed
      at all. The amount of blood found in the abdominal cavity ranged from 0 to 4500
      ml. Pre-existing liver steatosis showed no significant difference in injury
      pattern or bleeding from the liver. Three cases with liver haemangiomas and one
      with a liver cyst showed no lesion to their focal alteration. Because of the
      small number of cases, no statistical analysis was made concerning concomitant
      injuries such as head, thoracic or limb trauma. CONCLUSION: Higher grades of
      liver injury severity are associated with higher blood loss into the abdominal
      cavity. In addition, a patient with pre-existing liver steatosis seems not to be
      at any greater risk of having a larger rupture or having stronger bleeding from
      the liver after a blunt impact compared with a patient with a normal liver.

PMID- 22872076
TI  - Inappropriate use of the faecal occult blood test outside of the National Health
      Service colorectal cancer screening programme.
AB  - OBJECTIVE: The faecal occult blood test (FOBT) is the screening test validated
      for use in the National Health Service (NHS) Bowel Cancer Screening Programme
      (BCSP) after trials demonstrated a 16% reduction in colorectal cancer-specific
      mortality. FOBT is not validated for use outside the BCSP. The aim was to
      investigate the number of FOBTs performed outside of the NHS BCSP at a single
      centre. METHODS: All FOBTs performed over 1 year were identified. Basic patient
      demographics, requesting physician and FOBT results were obtained. Referrals and
      outcomes of the investigation following the FOBT were collected. RESULTS: A total
      of 758 FOBTs were requested in 701 patients (352 female; median age 69; range 16
      99). The majority (91%) were requested by general practitioners. A total of 515
      out of 758 tests (68%) were performed in patients outside the NHS BCSP age range.
      Thirty-seven out of 86 positive FOBTs were investigated, diagnosing four rectal
      cancers and two polyps. Forty-nine out of 87 patients with a positive FOBT were
      not investigated further by the requesting physician or the test repeated. Of the
      remaining 672 FOBTs, 615 were negative and 57 were either incomplete or
      unsuitable for analysis. A total of 111 patients (18%) were referred to hospital
      and 105 of these had FOBT performed as part of the referral process. CONCLUSION:
      Our study demonstrates significant misuse of the FOBT outside the NHS BCSP.
      Inappropriate use leads to false positives and exposes patients to unnecessary
      risk. False negatives provide reassurance to patients who may have symptoms that
      should be investigated. The FOBT should not be available to physicians in either
      primary or secondary care and be restricted to NHS BCSP.

PMID- 22872077
TI  - Conservative treatment of right-sided colonic diverticulitis.
AB  - BACKGROUND: Diverticulosis of the right colon occurs in a small percentage of
      patients in Western countries. Clinical presentation of right-sided colon
      diverticulitis is indistinguishable from that of acute appendicitis, and the
      majority of patients undergo surgical intervention for presumed appendicitis. The
      liberal use of diagnostic radiological modalities whenever appendicitis was
      suspected led to correct diagnosis and also to more preoperative diagnosis of
      right-sided diverticulitis, which consented conservative medical therapy in cases
      of uncomplicated right-sided diverticulitis. The aim of the study was to report
      the outcome in patients with right-sided diverticulitis diagnosed nonoperatively
      using computed tomography scanning and treated conservatively. METHODS: Patients
      with clinical and radiological diagnosis of cecal or right colon diverticulitis
      treated conservatively between January 2005 and December 2007 were included. The
      demographic and clinical data were retrospectively analyzed. RESULTS: Fifteen
      patients were included in this study. The median age was 52 years (range, 34-72
      years) and the duration of symptoms was 4 days (range, 1-9 days) before the
      diagnosis. The median hospital stay was 5 days (range, 1-9 days). All patients
      were successfully treated with medical therapy. During a median follow-up of 32
      months (range, 24-52 months) only one patient (6.6%) had a recurrent attack, and
      he was successfully treated again with medical therapy. CONCLUSION: The routine
      use of the computed tomography scan for abdominal pain in the right lower
      quadrant, and whenever right-sided diverticulitis is suspected, improves
      diagnosis and reduces surgical interventions. The current study provides
      additional data in support of conservative therapy as the initial treatment in
      acute right-sided diverticulitis, even in cases of recurrence.

PMID- 22872078
TI  - Direct cholangioscopy:  the North Shore experience.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) has long been a
      tool utilized by gastroenterologists for many years, but direct cholangioscopy
      has only recently begun to be available for regular use in clinical practice. The
      focus of this study was to evaluate the efficacy of a direct cholangioscopy
      system and its indications within our patient population. MATERIALS AND METHODS:
      This retrospective analysis was carried out at North Shore University Hospital.
      After obtaining institutional review board approval, the charts of patients who
      had undergone cholangioscopy from January 2007 through October 2011 were
      reviewed. An excel spreadsheet was created to record demographic information,
      significant laboratory data, indications for ERCP, ERCP findings, indication for
      cholangioscopy, findings, interventions, and biopsy results (if performed). A
      total of 34 cases were included in the final review. RESULTS: Cholangioscopy
      indications included incomplete or failed stone removal, biliary stricture
      evaluation, and retrieval of a migrated biliary stent, among others.
      Electrohydraulic lithotripsy was utilized with almost complete success in cases
      of previous failed stone removal. In 12 cases where a cholangioscopy-directed
      biopsy was performed, adequate tissue was obtained in all cases, and aided in the
      exclusion of malignancy. CONCLUSION: Direct cholangioscopy is a new technology
      whose use is currently limited in clinical practice, but is growing in
      popularity. Its continued recognition as an important adjunct in the management
      of biliary and pancreatic disease should prompt further research into its use of
      a prospective nature. Given the limited number of direct cholangioscopy cases
      performed every year, large, randomized-controlled studies evaluating its
      efficacy and effect on outcomes have not yet been performed, but small studies
      may still continue to yield valuable information on its efficacy and safety.

PMID- 22872079
TI  - Translating the effects of statins: from redox regulation to suppression of
      vascular wall inflammation.
AB  - Vascular oxidative stress is a key feature of atherogenesis, and targeting
      vascular redox signalling is a rational therapeutic goal in vascular disease
      pathogenesis. 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins are
      potent lipid-lowering drugs that improve cardiovascular outcomes. It is now
      widely accepted that cardiovascular disease prevention by statins is dependent
      not only on their lipid lowering effects, but also on their beneficial effects on
      vascular redox signalling. Cell culture and animal models have provided important
      findings on the effects of statins on vascular redox and nitric oxide
      bioavailability. Recent evidence from studies on human vessels has further
      enhanced our understanding of the "pleiotropic" effects of statins on vascular
      wall. Reversal of endothelial dysfunction in human vessels by statins is
      dependent on the mevalonate pathway and Rac1 inhibition. These critical steps are
      responsible for reducing NADPH-oxidase activity and improving tetrahydrobiopterin
      bioavailability and nitric oxide synthase (NOS) coupling in human vessels.
      However, mevalonate pathway inhibition has been also held responsible for some of
      the side effects observed after statin treatment. In this review we summarise the
      existing knowledge on the effects of statins on vascular biology by discussing
      key findings from basic science as well as recent evidence from translational
      studies in humans. Finally, we discuss emerging aspects of statin pleiotropy,
      such as their effects on adipose tissue biology and adipokine synthesis that may
      light additional mechanistic links between statin treatment and improvement of
      clinical outcome in primary and secondary prevention.

PMID- 22872080
TI  - Making waves: the rise and fall and rise of quantitative developmental biology.
AB  - The tenth annual RIKEN Center for Developmental Biology symposium 'Quantitative
      Developmental Biology' held in March 2012 covered a range of topics from coat
      colour patterning to the mechanics of morphogenesis. The studies presented shared
      a common theme in which a combination of physical theory, quantitative analysis
      and experiment was used to understand a specific cellular process in development.
      This report highlights these innovative studies and the long-standing questions
      in developmental biology that they seek to answer.

PMID- 22872081
TI  - A computational image analysis glossary for biologists.
AB  - Recent advances in biological imaging have resulted in an explosion in the
      quality and quantity of images obtained in a digital format. Developmental
      biologists are increasingly acquiring beautiful and complex images, thus creating
      vast image datasets. In the past, patterns in image data have been detected by
      the human eye. Larger datasets, however, necessitate high-throughput objective
      analysis tools to computationally extract quantitative information from the
      images. These tools have been developed in collaborations between biologists,
      computer scientists, mathematicians and physicists. In this Primer we present a
      glossary of image analysis terms to aid biologists and briefly discuss the
      importance of robust image analysis in developmental studies.

PMID- 22872082
TI  - Developmental and evolutionary diversity of plant MADS-domain factors: insights
      from recent studies.
AB  - Members of the MADS-box transcription factor family play essential roles in
      almost every developmental process in plants. Many MADS-box genes have conserved
      functions across the flowering plants, but some have acquired novel functions in
      specific species during evolution. The analyses of MADS-domain protein
      interactions and target genes have provided new insights into their molecular
      functions. Here, we review recent findings on MADS-box gene functions in
      Arabidopsis and discuss the evolutionary history and functional diversification
      of this gene family in plants. We also discuss possible mechanisms of action of
      MADS-domain proteins based on their interactions with chromatin-associated
      factors and other transcriptional regulators.

PMID- 22872083
TI  - Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain.
AB  - Neuronal migration, a key event during brain development, remains largely
      unexplored in the mesencephalon, where dopaminergic (DA) and GABA neurons
      constitute two major neuronal populations. Here we study the migrational
      trajectories of DA and GABA neurons and show that they occupy ventral
      mesencephalic territory in a temporally and spatially specific manner. Our
      results from the Pitx3-deficient aphakia mouse suggest that pre-existing DA
      neurons modulate GABA neuronal migration to their final destination, providing
      novel insights and fresh perspectives concerning neuronal migration and
      connectivity in the mesencephalon in normal as well as diseased brains.

PMID- 22872084
TI  - Anterior-posterior differences in HoxD chromatin topology in limb development.
AB  - A late phase of HoxD activation is crucial for the patterning and growth of
      distal structures across the anterior-posterior (A-P) limb axis of mammals.
      Polycomb complexes and chromatin compaction have been shown to regulate Hox loci
      along the main body axis in embryonic development, but the extent to which they
      have a role in limb-specific HoxD expression, an evolutionary adaptation defined
      by the activity of distal enhancer elements that drive expression of 5' Hoxd
      genes, has yet to be fully elucidated. We reveal two levels of chromatin topology
      that differentiate distal limb A-P HoxD activity. Using both immortalised cell
      lines derived from posterior and anterior regions of distal E10.5 mouse limb
      buds, and analysis in E10.5 dissected limb buds themselves, we show that there is
      a loss of polycomb-catalysed H3K27me3 histone modification and a chromatin
      decompaction over HoxD in the distal posterior limb compared with anterior.
      Moreover, we show that the global control region (GCR) long-range enhancer
      spatially colocalises with the 5' HoxD genomic region specifically in the distal
      posterior limb. This is consistent with the formation of a chromatin loop between
      5' HoxD and the GCR regulatory module at the time and place of distal limb bud
      development when the GCR participates in initiating Hoxd gene quantitative
      collinearity and Hoxd13 expression. This is the first example of A-P differences
      in chromatin compaction and chromatin looping in the development of the mammalian
      secondary body axis (limb).

PMID- 22872085
TI  - Dally and Notum regulate the switch between low and high level Hedgehog pathway
      signalling.
AB  - During development, secreted morphogens, such as Hedgehog (Hh), control cell fate
      and proliferation. Precise sensing of morphogen levels and dynamic cellular
      responses are required for morphogen-directed morphogenesis, yet the molecular
      mechanisms responsible are poorly understood. Several recent studies have
      suggested the involvement of a multi-protein Hh reception complex, and have
      hinted at an understated complexity in Hh sensing at the cell surface. We show
      here that the expression of the proteoglycan Dally in Hh-receiving cells in
      Drosophila is necessary for high but not low level pathway activity, independent
      of its requirement in Hh-producing cells. We demonstrate that Dally is necessary
      to sequester Hh at the cell surface and to promote Hh internalisation with its
      receptor. This internalisation depends on both the activity of the hydrolase
      Notum and the glycosyl-phosphatidyl-inositol (GPI) moiety of Dally, and indicates
      a departure from the role of the second glypican Dally-like in Hh signalling. Our
      data suggest that hydrolysis of the Dally-GPI by Notum provides a switch from low
      to high level signalling by promoting internalisation of the Hh-Patched ligand
      receptor complex.

PMID- 22872086
TI  - Hox genes regulate the onset of Tbx5 expression in the forelimb.
AB  - Tbx4 and Tbx5 are two closely related T-box genes that encode transcription
      factors expressed in the prospective hindlimb and forelimb territories,
      respectively, of all jawed vertebrates. Despite their striking limb type
      restricted expression pattern, we have shown that these genes do not participate
      in the acquisition of limb type-specific morphologies. Instead, Tbx4 and Tbx5
      play similar roles in the initiation of hindlimb and forelimb outgrowth,
      respectively. We hypothesized that different combinations of Hox proteins
      expressed in different rostral and caudal domains of the lateral plate mesoderm,
      where limb induction occurs, might be involved in regulating the limb type
      restricted expression of Tbx4 and Tbx5 and in the later determination of limb
      type-specific morphologies. Here, we identify the minimal regulatory element
      sufficient for the earliest forelimb-restricted expression of the mouse Tbx5 gene
      and show that this sequence is Hox responsive. Our results support a mechanism in
      which Hox genes act upstream of Tbx5 to control the axial position of forelimb
      formation.

PMID- 22872087
TI  - Focal adhesion kinase regulates actin nucleation and neuronal filopodia formation
      during axonal growth.
AB  - The establishment of neural circuits depends on the ability of axonal growth
      cones to sense their surrounding environment en route to their target. To achieve
      this, a coordinated rearrangement of cytoskeleton in response to extracellular
      cues is essential. Although previous studies have identified different
      chemotropic and adhesion molecules that influence axonal development, the
      molecular mechanism by which these signals control the cytoskeleton remains
      poorly understood. Here, we show that in vivo conditional ablation of the focal
      adhesion kinase gene (Fak) from mouse hippocampal pyramidal cells impairs axon
      outgrowth and growth cone morphology during development, which leads to
      functional defects in neuronal connectivity. Time-lapse recordings and in vitro
      FRAP analysis indicate that filopodia motility is altered in growth cones lacking
      FAK, probably owing to deficient actin turnover. We reveal the intracellular
      pathway that underlies this process and describe how phosphorylation of the actin
      nucleation-promoting factor N-WASP is required for FAK-dependent filopodia
      formation. Our study reveals a novel mechanism through which FAK controls
      filopodia formation and actin nucleation during axonal development.

PMID- 22872089
TI  - Multilayer mounting enables long-term imaging of zebrafish development in a light
      sheet microscope.
AB  - Light sheet microscopy techniques, such as selective plane illumination
      microscopy (SPIM), are ideally suited for time-lapse imaging of developmental
      processes lasting several hours to a few days. The success of this promising
      technology has mainly been limited by the lack of suitable techniques for
      mounting fragile samples. Embedding zebrafish embryos in agarose, which is common
      in conventional confocal microscopy, has resulted in severe growth defects and
      unreliable results. In this study, we systematically quantified the viability and
      mobility of zebrafish embryos mounted under more suitable conditions. We found
      that tubes made of fluorinated ethylene propylene (FEP) filled with low
      concentrations of agarose or methylcellulose provided an optimal balance between
      sufficient confinement of the living embryo in a physiological environment over 3
      days and optical clarity suitable for fluorescence imaging. We also compared the
      effect of different concentrations of Tricaine on the development of zebrafish
      and provide guidelines for its optimal use depending on the application. Our
      results will make light sheet microscopy techniques applicable to more fields of
      developmental biology, in particular the multiview long-term imaging of zebrafish
      embryos and other small organisms. Furthermore, the refinement of sample
      preparation for in toto and in vivo imaging will promote other emerging optical
      imaging techniques, such as optical projection tomography (OPT).

PMID- 22872088
TI  - Ribosomal biogenesis genes play an essential and p53-independent role in
      zebrafish pancreas development.
AB  - Mutations in the human Shwachman-Bodian-Diamond syndrome (SBDS) gene cause
      defective ribosome assembly and are associated with exocrine pancreatic
      insufficiency, chronic neutropenia and skeletal defects. However, the mechanism
      underlying these phenotypes remains unclear. Here we show that knockdown of the
      zebrafish sbds ortholog fully recapitulates the spectrum of developmental
      abnormalities observed in the human syndrome, and further implicate impaired
      proliferation of ptf1a-expressing pancreatic progenitor cells as the basis for
      the observed pancreatic phenotype. It is thought that diseases of ribosome
      assembly share a p53-dependent mechanism. However, loss of p53 did not rescue the
      developmental defects associated with loss of zebrafish sbds. To clarify the
      molecular mechanisms underlying the observed organogenesis defects, we performed
      transcriptional profiling to identify candidate downstream mediators of the sbds
      phenotype. Among transcripts displaying differential expression, functional group
      analysis revealed marked enrichment of genes related to ribosome biogenesis, rRNA
      processing and translational initiation. Among these, ribosomal protein L3 (rpl3)
      and pescadillo (pes) were selected for additional analysis. Similar to knockdown
      of sbds, knockdown or mutation of either rpl3 or pes resulted in impaired
      expansion of pancreatic progenitor cells. The pancreatic phenotypes observed in
      rpl3- and pes-deficient embryos were also independent of p53. Together, these
      data suggest novel p53-independent roles for ribosomal biogenesis genes in
      zebrafish pancreas development.

PMID- 22872090
TI  - A novel 3D mouse embryo atlas based on micro-CT.
AB  - The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype
      targeted knockout mouse strains throughout the whole mouse genome (23,000 genes)
      by 2021. A significant percentage of the generated mice will be embryonic lethal;
      therefore, phenotyping methods tuned to the mouse embryo are needed. Methods that
      are robust, quantitative, automated and high-throughput are attractive owing to
      the numbers of mice involved. Three-dimensional (3D) imaging is a useful method
      for characterizing morphological phenotypes. However, tools to automatically
      quantify morphological information of mouse embryos from 3D imaging have not been
      fully developed. We present a representative mouse embryo average 3D atlas
      comprising micro-CT images of 35 individual C57BL/6J mouse embryos at 15.5 days
      post-coitum. The 35 micro-CT images were registered into a consensus average
      image with our automated image registration software and 48 anatomical structures
      were segmented manually. We report the mean and variation in volumes for each of
      the 48 segmented structures. Mouse organ volumes vary by 2.6-4.2% on a linear
      scale when normalized to whole body volume. A power analysis of the volume data
      reports that a 9-14% volume difference can be detected between two classes of
      mice with sample sizes of eight. This resource will be crucial in establishing
      baseline anatomical phenotypic measurements for the assessment of mutant mouse
      phenotypes, as any future mutant embryo image can be registered to the atlas and
      subsequent organ volumes calculated automatically.

PMID- 22872091
TI  - The application of information theory to biochemical signaling systems.
AB  - Cell signaling can be thought of fundamentally as an information transmission
      problem in which chemical messengers relay information about the external
      environment to the decision centers within a cell. Due to the biochemical nature
      of cellular signal transduction networks, molecular noise will inevitably limit
      the fidelity of any messages received and processed by a cell's signal
      transduction networks, leaving it with an imperfect impression of its
      environment. Fortunately, Shannon's information theory provides a mathematical
      framework independent of network complexity that can quantify the amount of
      information that can be transmitted despite biochemical noise. In particular, the
      channel capacity can be used to measure the maximum number of stimuli a cell can
      distinguish based upon the noisy responses of its signaling systems. Here, we
      provide a primer for quantitative biologists that covers fundamental concepts of
      information theory, highlights several key considerations when experimentally
      measuring channel capacity, and describes successful examples of the application
      of information theoretic analysis to biological signaling.

PMID- 22872092
TI  - Diversity-oriented synthesis of 1-substituted 4-aryl-6-oxo-1,6-dihydropyridine-3
      carboxamides.
AB  - A simple five-step diversity-oriented synthesis of 1-substituted 4-aryl-6-oxo-1,6
      dihydropyridine-3-carboxamides was developed. Treatment of dimethyl 2
      ((dimethylamino)methylidene)-3-oxopentanedioate with twenty primary amines gave 1
      substituted methyl 4-hydroxy-6-oxo-1,6-dihydropyridine-3-carboxylates.
      Transformation into the corresponding 4-tosyloxy and 4-chloro derivatives,
      followed by Suzuki-Miyaura arylations gave a series of eleven N-substituted
      methyl 4-aryl-6-oxo-1,6-dihydropyridine-3-carboxylates. Combinatorial screening
      was employed to establish suitable reaction conditions for Suzuki-Miyaura
      arylation of N-alkylpyridones. Hydrolysis of the esters followed by parallel
      solution-phase amidation of the corresponding carboxylic acids with primary and
      secondary amines furnished a library of seventeen final products. 

PMID- 22872093
TI  - A giant coordination cage based on sulfonylcalix[4]arenes.
AB  - A strategy for building coordination cages by a [6 + 8] condensation of M(II)(4)
      calix SBUs and rigid ancillary ligands was successfully applied to a cobalt
      sulfonylcalix[4]arene system. A giant cage obtained with BTE ligands has an
      overall periphery diameter of 5.0 nm and an internal spherical cavity of 2.3 nm.

PMID- 22872094
TI  - Tanshinone IIA and astragaloside IV promote the migration of mesenchymal stem
      cells by up-regulation of CXCR4.
AB  - Mesenchymal stem cells (MSCs) have a therapeutic potential to treat
      cardiovascular diseases. However, a significant barrier to MSC therapy is
      insufficient MSC engraftment in ischemic myocardium after systemic
      administration. Here, we investigated the modulatory effects of tanshinone IIA
      and astragaloside IV on the migration of MSCs and further defined the underlying
      mechanisms. CXCR4 expression in MSCs was determined by using flow cytometry, real
      time PCR, and western blotting. The results showed that CXCR4 expression was
      significantly higher in tanshinone IIA- and astragaloside IV-stimulated MSCs than
      that of the control. MSC migration toward stromal cell-derived factor-1alpha (SDF
      1alpha) was studied using a transwell system. MSCs treated with tanshinone IIA
      and astragaloside IV showed stronger migration than that of the control.
      Moreover, this enhanced migration ability was abrogated by a CXCR4 inhibitor. In
      a rat acute myocardial infarction model, MSCs stimulated with tanshinone IIA and
      astragaloside IV were stained with Dio and injected into model rats via the tail
      vein. Dio-labeled cells in myocardium sections were observed by fluorescence
      microscopy. Tanshinone IIA- and astragaloside IV-stimulated MSCs showed enhanced
      capacities to home to ischemic myocardium sites. In addition, there was no
      significant difference in the SDF-1alpha expression among groups. These data
      suggest that tanshinone IIA and astragaloside IV regulate MSC mobilization, at
      least partially via modulation of the CXCR4 expression.

PMID- 22872095
TI  - Biochemical characteristics of the Ca2+ pumping ATPase in the peribacteroid
      membrane from broad bean root nodules.
AB  - Ca(2+)-ATPase in the peribacteroid membrane (PBM) of symbiosomes isolated from
      Vicia faba root nodules was characterized in terms of its hydrolytic and
      transport activities. Both activities were found to be pH-dependent and exhibit
      pH optimum at pH 7.0. Translocation of Ca(2+) through the PBM by the Ca(2+)
      ATPase was shown to be fueled by ATP and other nucleotide triphosphates in the
      following order: ATP > ITP ? GTP ? UTP ? CTP, the K m of the enzyme for MgATP
      being about 100 MUM. Ca-dependent ITP-hydrolytic activity of symbiosomes was
      investigated in the presence of the Ca-EGTA buffer system and showed the affinity
      of PBM Ca(2+)-ATPase for Ca(2+) of about 0.1 MUM. The transport activity of
      Ca(2+)-ATPase was inhibited by erythrosin B as well as orthovanadate, but
      markedly stimulated by calmodulin from bovine brain. These results allowed us to
      conclude that this enzyme belongs to IIB-type Ca(2+)-ATPases which are present in
      other plant membranes.

PMID- 22872096
TI  - Spin-glass freezing in a Ni-vermiculite intercalation compound.
AB  - We report on the magnetic properties of a Ni(2+)-vermiculite intercalation
      compound from Santa Olalla, Huelva (Spain). This modified vermiculite was studied
      by means of DC and AC magnetic measurements. The existence of two maxima in
      magnetic susceptibility below 10 K was interpreted in terms of the Cole-Cole
      formalism as being due to spin-glass freezing in this material. The temperature,
      frequency and external magnetic field dependences of these anomalies located at
      temperatures around 2-3 K and 8-10 K in the imaginary part of the magnetic
      susceptibility, chi", seem to suggest the existence of spin-relaxation phenomena
      between the magnetic moments of the Ni(2+) ions. A dynamic study of the
      relaxation processes associated with these phenomena considering the Cole-Cole
      formalism allows us to interpret the anomaly found at 2-3 K according to a law of
      activated dynamics, obtaining values for the critical exponent, psinu < 1,
      characteristic of a d = 2 spin-glass-like system, while the maximum observed in
      chi" at 8-10 K can be described by means of a law of standard dynamics with a
      value of the exponent z of around 5, representative of a d = 3 spin-glass-like
      system.

PMID- 22872097
TI  - Detection of microRNAs in microglia by real-time PCR in normal CNS and during
      neuroinflammation.
AB  - Microglia are cells of the myeloid lineage that reside in the central nervous
      system (CNS)(1). These cells play an important role in pathologies of many
      diseases associated with neuroinflammation such as multiple sclerosis (MS)(2).
      Microglia in a normal CNS express macrophage marker CD11b and exhibit a resting
      phenotype by expressing low levels of activation markers such as CD45. During
      pathological events in the CNS, microglia become activated as determined by
      upregulation of CD45 and other markers(3). The factors that affect microglia
      phenotype and functions in the CNS are not well studied. MicroRNAs (miRNAs) are a
      growing family of conserved molecules (~22 nucleotides long) that are involved in
      many normal physiological processes such as cell growth and differentiation(4)
      and pathologies such as inflammation(5). MiRNAs downregulate the expression of
      certain target genes by binding complementary sequences of their mRNAs and play
      an important role in the activation of innate immune cells including
      macrophages(6) and microglia(7). In order to investigate miRNA-mediated pathways
      that define the microglial phenotype, biological function, and to distinguish
      microglia from other types of macrophages, it is important to quantitatively
      assess the expression of particular microRNAs in distinct subsets of CNS-resident
      microglia. Common methods for measuring the expression of miRNAs in the CNS
      include quantitative PCR from whole neuronal tissue and in situ hybridization.
      However, quantitative PCR from whole tissue homogenate does not allow the
      assessment of the expression of miRNA in microglia, which represent only 5-15% of
      the cells of neuronal tissue. Hybridization in situ allows the assessment of the
      expression of microRNA in specific cell types in the tissue sections, but this
      method is not entirely quantitative. In this report we describe a quantitative
      and sensitive method for the detection of miRNA by real-time PCR in microglia
      isolated from normal CNS or during neuroinflammation using experimental
      autoimmune encephalomyelitis (EAE), a mouse model for MS. The described method
      will be useful to measure the level of expression of microRNAs in microglia in
      normal CNS or during neuroinflammation associated with various pathologies
      including MS, stroke, traumatic injury, Alzheimer's disease and brain tumors.

PMID- 22872098
TI  - Dynamics and thermodynamics of water around EcoRI bound to a minimally mutated
      DNA chain.
AB  - Water plays an important role in protein-DNA interactions. Here, we examine using
      molecular dynamics simulations the differences in the dynamic and thermodynamic
      properties of water in the interfacial and intercalating regions of EcoRI bound
      to the cognate and to a minimally mutated noncognate DNA chain. The results show
      that the noncognate complex is not only more hydrated than the cognate complex,
      but the interfacial waters in the noncognate complex exhibit a faster dynamics,
      which in turn reduces the hydrogen-bond lifetimes. Thus, the higher hydration,
      faster reorientation dynamics and faster hydrogen-bond-relaxation times of water,
      taken together, indicate that, even with a minimal mutation of the DNA sequence,
      the interfacial regions of the noncognate complex are more poised to allowing the
      protein to diffuse away than to promoting the formation of a stable complex.
      Alternatively, the results imply that the slowed water dynamics in the
      interfacial regions when the protein chances upon a cognate sequence allow the
      formation of a stable specific protein-DNA complex leading to catalytic action.

PMID- 22872099
TI  - FTO levels affect RNA modification and the transcriptome.
AB  - A block of single-nucleotide polymorphisms within intron 1 of the FTO (fat mass
      and obesity associated) gene is associated with variation in body weight.
      Previous works suggest that increased expression of FTO, which encodes a 2
      oxoglutarate-dependent nucleic acid demethylase, leads to increased body weight,
      although the underlying mechanism has remained unclear. To elucidate the function
      of FTO, we examined the consequences of altered FTO levels in cultured cells and
      murine brain. Here we show that a knockdown of FTO in HEK293 cells affects the
      transcripts levels of genes involved in the response to starvation, whereas
      overexpression of FTO affects the transcript levels of genes related to RNA
      processing and metabolism. Subcellular localization of FTO further strengthens
      the latter notion. Using immunocytochemistry and confocal laser scanning
      microscopy, we detected FTO in nuclear speckles and--to a lesser and varying
      extent--in the nucleoplasm and nucleoli of HEK293, HeLa and MCF-7 cells.
      Moreover, RNA modification analyses revealed that loss of Fto affects the 3
      methyluridine/uridine and pseudouridine/uridine ratios in total brain RNA. We
      conclude that altered levels of FTO have multiple and diverse consequences on RNA
      modifications and the transcriptome.

PMID- 22872100
TI  - The CDKL5 disorder is an independent clinical entity associated with early-onset
      encephalopathy.
AB  - The clinical understanding of the CDKL5 disorder remains limited, with most
      information being derived from small patient groups seen at individual centres.
      This study uses a large international data collection to describe the clinical
      profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information
      on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and
      females with MECP2 mutations (n=920) was sourced from the InterRett database.
      Available photographs of CDKL5 patients were examined for dysmorphic features.
      The proportion of CDKL5 patients meeting the recent Neul criteria for atypical
      RTT was determined. Logistic regression and time-to-event analyses were used to
      compare the occurrence of Rett-like features in those with MECP2 and CDKL5
      mutations. Most individuals with CDKL5 mutations had severe developmental delay
      from birth, seizure onset before the age of 3 months and similar non-dysmorphic
      features. Less than one-quarter met the criteria for early-onset seizure variant
      RTT. Seizures and sleep disturbances were more common than in those with MECP2
      mutations whereas features of regression and spinal curvature were less common.
      The CDKL5 disorder presents with a distinct clinical profile and a subtle facial,
      limb and hand phenotype that may assist in differentiation from other early-onset
      encephalopathies. Although mutations in the CDKL5 gene have been described in
      association with the early-onset variant of RTT, in our study the majority did
      not meet these criteria. Therefore, the CDKL5 disorder should be considered
      separate to RTT, rather than another variant.

PMID- 22872101
TI  - Clinical utility gene card for: MUTYH-associated polyposis (MAP), autosomal
      recessive colorectal adenomatous polyposis, multiple colorectal adenomas,
      multiple adenomatous polyps (MAP) - update 2012.

PMID- 22872102
TI  - Detection of copy-number variation in AUTS2 gene by targeted exonic array CGH in
      patients with developmental delay and autistic spectrum disorders.
AB  - Small genomic rearrangements and copy-number variations (CNVs) involving a single
      gene have been associated recently with many neurocognitive phenotypes, including
      intellectual disability (ID), behavioral abnormalities, and autistic spectrum
      disorders (ASDs). Such small CNVs in the Autism susceptibility candidate 2
      (AUTS2) gene have been shown to be associated with seizures, ID, and ASDs. We
      report four patients with small CNVs ranging in size between 133-319 kb that
      disrupt AUTS2. Two patients have duplications involving single exons, whereas two
      have deletions that removed multiple exons. All patients had developmental delay,
      whereas two patients had a diagnosis of ASDs. The CNVs were detected by an exon
      targeted array CGH with dense oligonucleotide coverage in exons of genes known or
      hypothesized to be causative of multiple human phenotypes. Our report further
      shows that disruption of AUTS2 results in a variety of neurobehavioral
      phenotypes. More importantly, it demonstrates the utility of targeted exon array
      as a highly sensitive clinical diagnostic tool for the detection of small genomic
      rearrangements in the clinically relevant regions of the human genome.

PMID- 22872103
TI  - Soyfoods and soybean products: from traditional use to modern applications.
AB  - Soybean products (soyfoods), reported as potential functional foods, are
      implicated in several health-enhancing properties, such as easing the symptoms of
      postmenopausal women, reducing the risk of osteoporosis, preventing
      cardiovascular disease, and antimutagenic effects. Isoflavone, for example, is
      one of the most important compounds abundantly found in soybean, mainly
      accounting for the health-enhancing properties as mentioned earlier. However,
      most biological activities of isoflavones are mainly attributed to their aglycone
      forms. It has also been demonstrated that isoflavone aglycones are absorbed
      faster and in greater amount than their glycosides in human intestines.
      Fortunately, deglycosylation of isoflavones can be achieved during fermentation
      process by several strains such as lactic acid bacteria, basidiomycetes,
      filamentous fungus, and Bacillus subtilis with their beta-glucosidase activity.
      This article presents an overview of soybean's chemistry, application, state-of
      the-art advances in soybean fermentation processing and products as well as their
      applications in food and pharmaceutical industries. Different compounds, such as
      isoflavone, dietary fibers, and proteins which exhibit significant bioactivities,
      are summarized. The roles of different microorganisms in bioconversion and
      enhancement of bioactivities of fermented soybean are also discussed.

PMID- 22872104
TI  - Study of the influence of sporulation conditions on heat resistance of
      Geobacillus stearothermophilus used in the development of biological indicators
      for steam sterilization.
AB  - Biological indicators are important tools in infection control via sterilization
      process monitoring. The use of a standardized spore crop with a well-defined heat
      resistance will guarantee the quality of a biological indicator. Ambient factors
      during sporulation can affect spore characteristics and properties, including
      heat resistance. The aim of this study is to evaluate the main sporulation
      factors responsible for heat resistance in Geobacillus stearothermophilus, a
      useful biological indicator for steam sterilization. A sequence of a three-step
      optimization of variables (initial pH, nutrient concentration, tryptone, peptone,
      beef extract, yeast extract, manganese sulfate, magnesium sulfate, calcium
      chloride and potassium phosphate) was carried out to screen those that have a
      significant influence on heat resistance of produced spores. The variable
      exerting greatest influence on G. stearothermophilus heat resistance during
      sporulation was found to be the initial pH. Lower nutrient concentration and
      alkaline pH around 8.5 tended to enhance decimal reduction time at 121  degrees C
      (D(121 degrees C)). A central composite design enabled a fourfold enhancement in
      heat resistance, and the model obtained accurately describes positive pH and
      negative manganese sulfate concentration influence on spore heat resistance.

PMID- 22872105
TI  - Population impact of depression on functional disability in elderly: results from
      "Sao Paulo Ageing & Health Study" (SPAH).
AB  - With the fast population aging, functional disability among the elderly is
      becoming a major public health issue. Depression is highly prevalent in this
      phase of life and may be associated with a significant proportion of the
      disability among elderly populations. We investigated the association of
      depressive symptoms and ICD-10 depression with functional disability in older
      adults and estimated the corresponding population attributable fractions (PAF). A
      cross-sectional one-phase population-based study was carried out with 2,072
      individuals aged 65 years or over living in a low-income area of Sao Paulo,
      Brazil. Depressive symptoms and ICD-10 depression were assessed with the
      Geriatric Mental State and the Neuropsychiatric Inventory. We assessed functional
      disability with the WHO Disability Assessment Schedule Instrument. Prevalence
      Ratios and PAF were calculated using Poisson regression. The prevalence of
      depressive symptoms and ICD-10 depression was 21.4 and 4.8 %, respectively.
      Depression and depressive symptoms were strongly associated with high functional
      disability, even after adjustment for demographic factors, socioeconomic
      conditions, physical morbidities, and dementia. The PAFs for depressive symptoms
      and ICD-10 depression were 12.0 % for each of the psychiatric morbidity.
      Depressive symptoms contributed as much as ICD-10 depression to the population
      burden of functional disability in the elderly. Effective management of
      clinically significant depressive symptoms, delivered mainly at the primary care
      level, may reduce the total population disability.

PMID- 22872106
TI  - [Diffuse liver diseases].

PMID- 22872107
TI  - Impact of a rural village women (Asha) intervention on adherence to
      antiretroviral therapy in southern India.
AB  - BACKGROUND: Despite the increased prevalence of HIV in the rural female
      population of India, adherence to antiretroviral therapy continues to be low
      because of several barriers that discourage rural women. OBJECTIVES: This study
      aims to assess the effectiveness of an intervention (Asha-Life) delivered by
      Accredited Social Health Activists (Asha) to improve antiretroviral therapy
      adherence of rural women living with AIDS in India compared with that of a usual
      care group. METHODS: Sixty-eight rural women living with AIDS, aged 18-45 years,
      participated in a prospective, randomized pilot clinical trial and were assessed
      for several factors affecting adherence, such as sociodemographic
      characteristics, health history, CD4 cell count, enacted stigma, depressive
      symptomology, help getting antiretroviral therapy, and perceived therapy
      benefits. RESULTS: Findings at 6 months revealed that, although both groups
      improved their adherence to antiretroviral therapy, there was greater improvement
      in the Asha-Life group (p < .001), who reported a greater reduction in barriers
      to antiretroviral therapy than those in the usual care group. DISCUSSION:
      Antiretroviral therapy adherence showed significant increase in the Asha-Life
      cohort in which basic education on HIV/AIDS, counseling on antiretroviral
      therapy, support from Ashas, financial assistance, and better nutrition, was
      provided. The Asha-Life intervention may have great potential in improving
      antiretroviral therapy adherence and decreasing barriers among rural women living
      with AIDS in India.

PMID- 22872109
TI  - Do we know enough about the immune pathogenesis of acute coronary syndromes to
      improve clinical practice?
AB  - Morbidities related to atherosclerosis, such as acute coronary syndromes (ACS)
      including unstable angina and myocardial infarction, remain leading causes of
      mortality. Unstable plaques are inflamed and infiltrated with macrophages and T
      lymphocytes. Activated dendritic cells interact with T cells, yielding
      predominantly Th1 responses involving interferon-gamma (IFN-gamma) and tumour
      necrosis factor-alpha (TNF-alpha), while the role of interleukin 17 (IL-17) is
      questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern
      recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4)
      is characteristic for unstable plaque. Inflammation modifies platelet and fibrin
      clot characteristics, which are critical for ACS. Understanding of the
      inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative
      stress and immune regulation, will allow for the detection of subjects at risk,
      through the use of novel biomarkers and imaging techniques including
      intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI)
      and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET).
      Moreover, understanding the specific inflammatory pathways of plaque rupture and
      atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet
      drugs are anti-inflammatory, but importance of immune events in ACS warrants the
      introduction of novel, specific treatments directed either on cytokines, TLRs or
      inflammasomes. While the prime time for the introduction of immunologically
      inspired diagnostic tests and treatments for atherosclerosis have not come yet,
      we are closer than ever before to finally being able to benefit from this vast
      body of experimental and clinical evidence. This paper provides a comprehensive
      review of the role of the immune system and inflammation in ACS.

PMID- 22872110
TI  - Emotions and chronic illness.

PMID- 22872108
TI  - D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems.
AB  - D-Aspartate (D-Asp) is an endogenous amino acid in the central nervous and
      reproductive systems of vertebrates and invertebrates. High concentrations of D
      Asp are found in distinct anatomical locations, suggesting that it has specific
      physiological roles in animals. Many of the characteristics of D-Asp have been
      documented, including its tissue and cellular distribution, formation and
      degradation, as well as the responses elicited by D-Asp application. D-Asp
      performs important roles related to nervous system development and hormone
      regulation; in addition, it appears to act as a cell-to-cell signaling molecule.
      Recent studies have shown that D-Asp fulfills many, if not all, of the
      definitions of a classical neurotransmitter-that the molecule's biosynthesis,
      degradation, uptake, and release take place within the presynaptic neuron, and
      that it triggers a response in the postsynaptic neuron after its release.
      Accumulating evidence suggests that these criteria are met by a heterogeneous
      distribution of enzymes for D-Asp's biosynthesis and degradation, an appropriate
      uptake mechanism, localization within synaptic vesicles, and a postsynaptic
      response via an ionotropic receptor. Although D-Asp receptors remain to be
      characterized, the postsynaptic response of D-Asp has been studied and several L
      glutamate receptors are known to respond to D-Asp. In this review, we discuss the
      current status of research on D-Asp in neuronal and neuroendocrine systems, and
      highlight results that support D-Asp's role as a signaling molecule.

PMID- 22872112
TI  - Quantile regression for hypothesis testing and hypothesis screening at the dawn
      of big data.

PMID- 22872113
TI  - Can nonrandomized studies on the safety of antidepressants during pregnancy
      convincingly beat confounding, chance, and prior beliefs?

PMID- 22872114
TI  - Adolphe quetelet:  statistician and more.

PMID- 22872115
TI  - Using Twitter to measure behavior patterns.

PMID- 22872116
TI  - Do "personal stories" improve response rates?

PMID- 22872117
TI  - Incidence trends of malignant parotid gland tumors in Swedish and nordic adults
      1970 to 2009.

PMID- 22872118
TI  - Incidence shifts within central nervous system malignancies.

PMID- 22872119
TI  - Effects of local and Saharan particles on cardiovascular disease mortality.

PMID- 22872120
TI  - Evaluating percentiles of survival.

PMID- 22872121
TI  - Visualizing a 3-dimensional receiver operating characteristic-cost space.

PMID- 22872122
TI  - Using propensity scores to reduce case-control selection bias.

PMID- 22872124
TI  - Spin-wave excitations in superlattices self-assembled in multiferroic single
      crystals.
AB  - Spin-wave excitations revealed in the dynamically equilibrated one-dimensional
      superlattices formed due to phase separation and charge carrier self-organization
      in doped single crystals of Eu(0.8)Ce(0.2)Mn(2)O(5) and Tb(0.95)Bi(0.05)MnO(3)
      multiferroics are discussed. Similar excitations, but having lower intensities,
      were also observed in undoped RMn(2)O(5) (R=Eu, Er, Tb, Bi). This suggests that a
      charge transfer between manganese ions with different valences, which give rise
      to the superlattice formation, occurs in undoped multiferroics as well. The spin
      excitations observed in the native superlattices represent a set of homogeneous
      spin-wave resonances excited in individual superlattice layers. The positions of
      these resonances depend on the relation between the numbers of Mn(3+) and Mn(4+)
      ions, charge carrier concentrations, and barrier depths in the superlattice
      layers. It has been found that the spin-wave excitations observed in the
      frequency interval studied (30-50 GHz) form two spin-wave minibands with a gap
      between them.

PMID- 22872125
TI  - Targeting cancer cells: controlling the binding and internalization of antibody
      functionalized capsules.
AB  - The development of nanoengineered particles, such as polymersomes, liposomes, and
      polymer capsules, has the potential to offer significant advances in vaccine and
      cancer therapy. However, the effectiveness of these carriers has the potential to
      be greatly improved if they can be specifically delivered to target cells. We
      describe a general method for functionalizing nanoengineered polymer capsules
      with antibodies using click chemistry and investigate their interaction with
      cancer cells in vitro. The binding efficiency to cells was found to be dependent
      on both the capsule-to-cell ratio and the density of antibody on the capsule
      surface. In mixed cell populations, more than 90% of target cells bound capsules
      when the capsule-to-target cell ratio was 1:1. Strikingly, greater than 50% of
      target cells exhibited capsules on the cell surface even when the target cells
      were present as less than 0.1% of the total cell population. Imaging flow
      cytometry was used to quantify the internalization of the capsules, and the
      target cells were found to internalize capsules efficiently. However, the role of
      the antibody in this process was determined to enhance accumulation of capsules
      on the cell surface rather than promote endocytosis. This represents a
      significant finding, as this is the first study into the role antibodies play in
      internalization of such capsules. It also opens up the possibility of targeting
      these capsules to cancer cells using targeting molecules that do not trigger an
      endocytic pathway. We envisage that this approach will be generally applicable to
      the specific targeting of a variety of nanoengineered materials to cells.

PMID- 22872126
TI  - NADH fluorescence imaging of isolated biventricular working rabbit hearts.
AB  - Since its inception by Langendorff(1), the isolated perfused heart remains a
      prominent tool for studying cardiac physiology(2). However, it is not well-suited
      for studies of cardiac metabolism, which require the heart to perform work within
      the context of physiologic preload and afterload pressures. Neely introduced
      modifications to the Langendorff technique to establish appropriate left
      ventricular (LV) preload and afterload pressures(3). The model is known as the
      isolated LV working heart model and has been used extensively to study LV
      performance and metabolism(4-6). This model, however, does not provide a properly
      loaded right ventricle (RV). Demmy et al. first reported a biventricular model as
      a modification of the LV working heart model(7, 8). They found that stroke
      volume, cardiac output, and pressure development improved in hearts converted
      from working LV mode to biventricular working mode(8). A properly loaded RV also
      diminishes abnormal pressure gradients across the septum to improve septal
      function. Biventricular working hearts have been shown to maintain aortic output,
      pulmonary flow, mean aortic pressure, heart rate, and myocardial ATP levels for
      up to 3 hours(8). When studying the metabolic effects of myocardial injury, such
      as ischemia, it is often necessary to identify the location of the affected
      tissue. This can be done by imaging the fluorescence of NADH (the reduced form of
      nicotinamide adenine dinucleotide)(9-11), a coenzyme found in large quantities in
      the mitochondria. NADH fluorescence (fNADH) displays a near linearly inverse
      relationship with local oxygen concentration(12) and provides a measure of
      mitochondrial redox state(13). fNADH imaging during hypoxic and ischemic
      conditions has been used as a dye-free method to identify hypoxic regions(14, 15)
      and to monitor the progression of hypoxic conditions over time(10). The objective
      of the method is to monitor the mitochondrial redox state of biventricular
      working hearts during protocols that alter the rate of myocyte metabolism or
      induce hypoxia or create a combination of the two. Hearts from New Zealand white
      rabbits were connected to a biventricular working heart system (Hugo Sachs
      Elektronik) and perfused with modified Krebs-Henseleit solution(16) at 37 
      degrees C. Aortic, LV, pulmonary artery, and left & right atrial pressures were
      recorded. Electrical activity was measured using a monophasic action potential
      electrode. To image fNADH, light from a mercury lamp was filtered (350+/-25 nm)
      and used to illuminate the epicardium. Emitted light was filtered (460+/-20 nm)
      and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular
      working hearts during different pacing rates are presented. The combination of
      the heart model and fNADH imaging provides a new and valuable experimental tool
      for studying acute cardiac pathologies within the context of realistic
      physiological conditions.

PMID- 22872127
TI  - Abattoir survey of abomasal lesions associated with ostertagiosis in adult
      cattle.

PMID- 22872128
TI  - Sensitivity and specificity of MRI for detecting facial nerve abnormalities in
      dogs with facial neuropathy.
AB  - Idiopathic facial neuropathy in dogs is conventionally diagnosed by exclusion of
      structural and metabolic causes of a single cranial neuropathy. To investigate
      the reliability and validity of MRI for supporting a diagnosis of facial
      neuropathy in dogs, we examined MR images of the brainstem from 20 dogs with
      presumed idiopathic facial neuropathy, and 20 control dogs. Two different types
      of MRI sequence were compared: volumetric interpolated breath-hold examination
      MRI (VIBE-MRI), and conventional T1-weighted MRI. Three independent observers,
      blinded to the case details, were presented with VIBE-MR images in a random
      order, and were required to indicate the presence of hyperintensity of the facial
      nerve following intravenous contrast administration. The vestibulocochlear nerve
      was also assessed, and the whole process was repeated for conventional post
      contrast T1-weighted images. Following contrast administration, the sensitivity
      of VIBE-MRI for detecting facial nerve abnormalities ranged from 86 per cent to
      96 per cent, and the specificity from 87 per cent to 92 per cent; conventional T1
      weighted images yielded a sensitivity of only 39 per cent - 65 per cent, and a
      specificity of 94 per cent - 96 per cent. MRI was not a sensitive detector of
      vestibulocochlear nerve abnormalities in 14 dogs with concurrent vestibular
      dysfunction. This study shows that VIBE-MRI is a robust technique for confirming
      presumed idiopathic facial neuropathy in dogs, and suggests an inflammatory
      component to this condition in a high proportion of dogs.

PMID- 22872129
TI  - From aromaticity to self-organized criticality in graphene.
AB  - The unique properties of graphene are rooted in its peculiar electronic structure
      where effects of electron delocalization are pivotal. We show that the
      traditional view of delocalization as formation of a local or global aromatic
      bonding framework has to be expanded in this case. A modification of the pi
      electron system of a finite-size graphene substrate results in a scale-invariant
      response in the relaxation of interatomic distances and reveals self-organized
      criticality as a mode of delocalized bonding. Graphene is shown to belong to a
      diverse class of finite-size extended systems with simple local interactions
      where complexity emerges spontaneously under very general conditions that can be
      a critical factor controlling observable properties such as chemical activity,
      electron transport, and spin-polarization.

PMID- 22872130
TI  - Stress testing for the evaluation of patients with mitral regurgitation.
AB  - PURPOSE OF REVIEW: The emerging role of stress and particularly exercise
      echocardiography in mitral regurgitation has been recently emphasized. In fact,
      the evaluation of mitral regurgitation only under resting conditions might
      underestimate the full impact of the lesion and its clinical effects. RECENT
      FINDINGS: Exercise echocardiography can identify what otherwise might be
      considered as a moderate valve disease. Recently, worsening of mitral
      regurgitation severity, marked increase in pulmonary arterial pressure, limited
      contractile reserve, and impaired exercise capacity, together with the occurrence
      of symptoms during exercise echocardiography, provide the clinician with
      diagnostic and prognostic information that can contribute importantly to identify
      a subset of patients at higher risk, who may benefit from elective mitral valve
      surgery. SUMMARY: Exercise echocardiography has the advantages of its wide
      availability, low cost, and versatility for the assessment of mitral
      regurgitation severity. Furthermore, exercise echocardiography can help to unmask
      patients at a more advanced stage of the disease and could improve the management
      and the timing of surgery.

PMID- 22872131
TI  - Subclinical atherosclerosis imaging comes of age:  coronary artery calcium in
      primary prevention.
AB  - PURPOSE OF REVIEW: The goal of this review is to update the contributions of
      subclinical atherosclerosis imaging of coronary artery calcified plaque (CAC) to
      the primary prevention of coronary artery disease. RECENT FINDINGS: Recent
      articles have increased support for the following: superiority of CAC determined
      risk to conventional risk factor-based paradigms, reclassification of risk by
      CAC, serial CAC scanning to assess the efficacy of therapy, CAC evaluation of
      high-risk groups (diabetes and other disease states characterized by
      inflammation), and redefinition of normal and abnormal lipids, ideal treatment
      goals and residual risk, as well as statin potency. SUMMARY: The paradigm shifts
      implicit in the supremacy of CAC herald a transformation in primary prevention
      from conventional risk factor paradigms to the evaluation of the disease itself
      by subclinical atherosclerosis imaging.

PMID- 22872132
TI  - Is a cardioprotective action of alcohol a myth?
AB  - PURPOSE OF REVIEW: Numerous epidemiological studies have demonstrated that light
      to moderate alcohol consumption is associated with reduced risk of cardiovascular
      disease (CVD). The purpose of this review is to discuss the potential CV benefit
      of alcohol consumption with a particular focus on the findings of publications
      appearing within the past 2 years. RECENT FINDINGS: Results of observational
      studies and meta-analyses are largely concordant in suggesting the possibility of
      a beneficial effect of alcohol on CVD via several mechanisms, including actions
      on lipid metabolism and hemostatic factors. There are, however, studies that do
      not find the classic U-shaped association between alcohol consumption and CVD.
      Recent data suggest that the findings of coronary protection by alcohol
      consumption may be partly due to misclassification and confounding factors.
      Drinking patterns appear to be important factors to take into account when
      interpreting the results of epidemiological studies. SUMMARY: No data are
      currently available to directly support a causal relationship between alcohol
      intake and CVD. As well-conducted randomized studies assessing the causal role of
      alcohol in cardioprotection are not feasible, future epidemiological studies
      evaluating the relationship between alcohol and CVD should carefully choose the
      covariates in any multivariate analysis. It remains premature to promote alcohol
      consumption as a basis for CV protection.

PMID- 22872133
TI  - Chiral Bronsted acid catalyzed enantioselective allenylation of aldehydes.
AB  - A versatile and highly enantioselective chiral Bronsted acid-catalyzed
      allenylation of aldehydes with propargyl borolane is reported. The reaction is
      shown to be practical and quite general with a broad substrate scope covering
      aryl, heteroaryl, alpha,beta-unsaturated, and aliphatic aldehydes.

PMID- 22872134
TI  - Growth differentiation factor-15 upregulates interleukin-6 to promote
      tumorigenesis of prostate carcinoma PC-3 cells.
AB  - Growth differentiation factor-15 (GDF15), a member of the transforming growth
      factor-beta superfamily, is associated with human cancer progress. We evaluated
      the role GDF15 plays in tumorigenesis of prostate carcinoma PC-3 cells. Results
      from real-time RT-PCR and ELISA revealed that expression of GDF15 was
      approximately threefold higher in LNCaP cells than in PC-3 cells. Other prostate
      cell lines (PZ-HPV-7, CA-HPV-10, and DU145 cells) expressed extremely low levels
      of GDF15. Stable overexpression of GDF15 in PC-3 cells enhanced the degree of
      cell proliferation and invasion as shown in the (3)H-thymidine incorporation
      assay and in the Matrigel invasion assay respectively. Soft agar assays and
      xenograft animal studies indicated that overexpression of GDF15 in PC-3 cells
      increased tumorigenesis in vitro and in vivo. Results from RT-PCR, immunoblot,
      and reporter assays revealed that overexpression of GDF15 resulted in decreased
      expression of maspin and upregulation of interleukin-6 (IL6), matriptase, and N
      myc downstream-regulated gene 1 (NDRG1) expression. Further studies revealed that
      overexpression of IL6 enhanced GDF15 expression in LNCaP cells while knockdown of
      IL6 blocked the expression of GDF15 in PC-3 cells, suggesting that expression of
      GDF15 is upregulated by IL6. This study demonstrated that expression of GDF15
      induces cell proliferation, invasion, and tumorigenesis of prostate carcinoma PC
      3 cells. The enhancement of tumorigenesis and invasiveness of prostate carcinoma
      cells that stably overexpress GDF15 may be caused by the dysregulation of maspin,
      matriptase, and IL6 gene expression. The expression of GDF15 and IL6 is
      controlled via a positive feedback loop in PC-3 cells.

PMID- 22872135
TI  - Chromatin immunoprecipitation: advancing analysis of nuclear hormone signaling.
AB  - Recent decades have been filled with groundbreaking research in the field of
      endocrine hormone signaling. Pivotal events like the isolation and purification
      of the estrogen receptor, the cloning of glucocorticoid receptor cDNA, or
      dissemination of nuclear hormone receptor (NHR) DNA binding sequences are well
      recognized for their contributions. However, the novel genome-wide and gene
      specific information obtained over the last decade describing NHR association
      with chromatin, cofactors, and epigenetic modifications, as well as their role in
      gene regulation, has been largely facilitated by the adaptation of the chromatin
      immunoprecipitation (ChIP) technique. Use of ChIP-based technologies has taken
      the field of hormone signaling from speculating about the transcription-enabling
      properties of acetylated chromatin and putative transcription (co-)factor genomic
      occupancy to demonstrating the detailed, stepwise mechanisms of factor binding
      and transcriptional initiation; from treating hormone-induced transcription as a
      steady-state event to understanding its dynamic and cyclic nature; from looking
      at the DNA sequences recognized by various DNA-binding domains in vitro to
      analyzing the cell-specific genome-wide pattern of nuclear receptor binding and
      interpreting its physiological implications. Not only have these events propelled
      hormone research, but, as some of the pioneering studies, have also contributed
      tremendously to the field of molecular endocrinology as a whole. In this review,
      we give a brief summary of some of the most important discoveries in hormone
      signaling using ChIP and other derivative techniques and speculate on what the
      future may hold.

PMID- 22872136
TI  - Beam characteristics and stopping-power ratios of small radiosurgery photon
      beams.
AB  - Small megavoltage (MV) photon fields of dimensions less than 3 * 3 cm(2) are
      increasingly being used in modern radiation therapy. To our knowledge, small beam
      characteristics and dosimetric parameters, such as the energy spectra, particle
      fluence, and water-to-air stopping-power ratios (SPRs) directly affect the
      accuracy of small field dosimetry. This study presents the characteristics of
      small photon beams and investigates the variations of energy spectra of photons
      and electrons as a function of field size and their effects on the water-to-air
      SPRs for field sizes ranging from a small 4 mm diameter circular field to a 10 *
      10 cm(2) field. It sheds light on the differences between small fields collimated
      by the cone accessory and X- and Y-jaws and on beam characteristics outside the
      primary radiation fields. In addition, we also investigated the use of an
      'intermediate machine-specific-reference field' (Alfonso et al 2008 Med. Phys. 35
      5179-86) to determine if the variations between a small and a reference field can
      be eased by introducing an intermediate 4 * 4 cm(2) field instead of a standard
      10 * 10 cm(2) reference field. The Monte Carlo simulation codes BEAMnrc,
      DOSXYZnrc and SPRRZnrc were used in this study. The accelerator head and circular
      cone accessory were simulated in detail including two designs of flattening
      filters: one for a standard-dose rate (100-600 MU min(-1)) and the other for a
      high-dose rate (1000 MU min(-1)) 6 MV beam. The mean energy of photons at depths
      (1.5-30 cm) in water are 1.72-2.36 MeV, 1.55-1.97 MeV, and 1.44-1.74 MeV for
      field sizes of 4 mm diameter, 4 * 4 cm(2), and 10 * 10 cm(2), respectively. The
      mean energy also varies significantly for electrons at depths (1.5-30 cm): 0.99
      1.25 MeV, 0.94-1.09 MeV, and 0.93-1.04 MeV for field sizes of 4 mm, 4 * 4 cm(2),
      and 10 * 10 cm(2), respectively. The calculated water-to-air SPRs at depths (1.5
      30 cm) are 1.120-1.113, 1.121-1.117, and 1.122-1.119 for field sizes of 4 mm, 4 *
      4 cm(2) and 10 * 10 cm(2), respectively. Although the differences in mean energy
      are > 20% for photons and > 5% for electrons between 4 mm field and 10 * 10
      cm(2), the effects on the water-to-air SPRs are small (<0.5%). For detectors with
      responses to energy changes that are not negligible, significant energy
      variations between small fields and the reference 10 * 10 cm(2) field may have a
      significant impact on the dosimetry accuracy. However, the use of an intermediate
      field is capable of greatly reducing these energy variations. This study also
      found negligible differences in dosimetric parameters between beams with
      different flattening filters and different incident electron energies on the
      target when each has the same beam quality k(Q) values specified by %dd(10)(x).

PMID- 22872137
TI  - Co+-H interaction inspired alternate coordination geometries of biologically
      important cob(I)alamin: possible structural and mechanistic consequences for
      methyltransferases.
AB  - A detailed computational analysis employing density functional theory (DFT),
      atoms in molecules, and quantum mechanics/molecular mechanics (QM/MM) tools has
      been performed to investigate the primary coordination environment of
      cob(I)alamin (Co(+)Cbx), which is a ubiquitous B(12) intermediate in
      methyltransferases and ATP:corrinoid adenosyltransferases. The DFT calculations
      suggest that the simplified (Co(+)Cbl) as well as the complete (Co(+)Cbi)
      complexes can adapt to the square pyramidal or octahedral coordination geometry
      owing to the unconventional H-bonding between the Co(+) ion and its axial
      ligands. These Co(+)-H bonds contain appreciable amounts of electrostatic, charge
      transfer, long-range correlation, and dispersion components. The computed
      reduction potentials of the Co(2+)/Co(+) couple imply that the Co(+)-H(H(2)O)
      interaction causes a greater anodic shift [5-98 mV vs. the normal hydrogen
      electrode (NHE) in chloroform solvent] than the analogous Co(+)-H(imidazole)
      interaction (1 mV vs. NHE) in the reduction potential of the Co(2+)/Co(+) couple.
      This may explain why a beta-axial H(2)O ligand has specifically been found in the
      active sites of certain methyltransferases. The QM/MM analysis of methionine
      synthase bound Co(+)Cbx (Protein Data Bank ID 1BMT, resolution 3.0 A) indicates
      that the enzyme-bound Co(+)Cbx can also form a Co(+)-H bond, but can only exist
      in square pyramidal form because of the steric constraints imposed by the
      cellular environment. The present calculations thus support a recently proposed
      alternate mechanism for the enzyme-bound Co(2+)/Co(+) reduction that involves the
      conversion of square pyramidal Co(2+)Cbx into square pyramidal Co(+)Cbx (Kumar
      and Kozlowski in Angew. Chem. Int. Ed. 50:8702-8705, 2011).

PMID- 22872138
TI  - EPR and (57)Fe ENDOR investigation of 2Fe ferredoxins from Aquifex aeolicus.
AB  - We have employed EPR and a set of recently developed electron nuclear double
      resonance (ENDOR) spectroscopies to characterize a suite of [2Fe-2S] ferredoxin
      clusters from Aquifex aeolicus (Aae Fd1, Fd4, and Fd5). Antiferromagnetic
      coupling between the Fe(II), S = 2, and Fe(III), S = 5/2, sites of the [2Fe
      2S](+) cluster in these proteins creates an S = 1/2 ground state. A complete
      discussion of the spin-Hamiltonian contributions to g includes new symmetry
      arguments along with references to related FeS model compounds and their symmetry
      and EPR properties. Complete (57)Fe hyperfine coupling (hfc) tensors for each
      iron, with respective orientations relative to g, have been determined by the use
      of "stochastic" continuous wave and/or "random hopped" pulsed ENDOR, with the
      relative utility of the two approaches being emphasized. The reported hyperfine
      tensors include absolute signs determined by a modified pulsed ENDOR saturation
      and recovery (PESTRE) technique, RD-PESTRE-a post-processing protocol of the "raw
      data" that comprises an ENDOR spectrum. The (57)Fe hyperfine tensor components
      found by ENDOR are nicely consistent with those previously found by Mossbauer
      spectroscopy, while accurate tensor orientations are unique to the ENDOR
      approach. These measurements demonstrate the capabilities of the newly developed
      methods. The high-precision hfc tensors serve as a benchmark for this class of
      FeS proteins, while the variation in the (57)Fe hfc tensors as a function of
      symmetry in these small FeS clusters provides a reference for higher-nuclearity
      FeS clusters, such as those found in nitrogenase.

PMID- 22872139
TI  - The association of strategic group and organizational culture with hospital
      performance in China.
AB  - BACKGROUND: The policy environment in China is rapidly changing. Strategic
      planning may enable hospitals to respond more effectively to changes in their
      external environment, little evidence exists on the extent to which public
      hospitals in China adopt different strategies and the relationship between
      strategic decision-making and hospital performance. PURPOSES: The purposes of our
      study were to determine the extent to which different hospitals adopt different
      strategies, whether strategies are associated with organizational culture and
      whether hospital strategies are associated with hospital performance.
      METHODOLOGY: Presidents (or vice presidents), employees, and patients from 87
      public hospitals were surveyed during 2009. Measures of strategic group were
      developed using cluster analysis based on the three dimensions of product
      position, competitive posture, and market position. Culture was measured using a
      tool developed by the investigators. Performance was measured based on
      profitability, patient satisfaction, and employee satisfaction with overall
      hospital development in the recent 5 years. The association of strategic group
      and organizational culture with hospital performance was analyzed using
      multivariate models. FINDINGS: Chinese public general hospitals were classified
      into five strategic groups that had significant differences in product
      positioning, competitive posture, and market position. Hospitals of similar types
      based on regulation adopted different strategies. Organizational culture was not
      strongly associated with hospital strategic group. Although strategic group was
      associated with hospital profitability and patient satisfaction in the models
      with or without control for hospital location, these effects did not persist
      after controlling for organizational culture, hospital level, and hospital
      location. PRACTICE IMPLICATIONS: It is important for public hospitals in China to
      make effective strategic planning and align their organizational culture with the
      strategies for better execution and therefore better performance. Moreover, the
      method of hospital strategic grouping in the study provides a new way to analyze
      management issues within a strategic group and between strategic groups.

PMID- 22872140
TI  - The effects of sodium diethyldithiocarbamate in fibroblasts V79 cells in relation
      to cytotoxicity, antioxidative enzymes, glutathione, and apoptosis.
AB  - Sodium diethyldithiocarbamate (DETC) is the main metabolite of disulfiram.
      Recently, we reported that mechanism of disulfiram cytotoxicity in V79 cells
      might be partially connected with thiol redox-state imbalance. Here, we examined
      the effect of DETC on the level of intracellular glutathione (GSH), protein
      oxidation (measured as PC-protein carbonyl content), lipid peroxidation (measured
      as TBARS-thiobarbituric acid reactive substances), antioxidant enzymatic defense,
      as well as on apoptosis. We used V79 Chinese hamster fibroblasts cells with and
      without modulated glutathione (GSH) level by N-acetyl-L-cysteine (NAC). We showed
      that treatment with DETC at concentrations that cause a moderate increase in
      thiol-state imbalance but not cell death stimulates oxidative stress measured as
      increased level of PC and TBARS, adaptive response of GSH-related enzymes and
      apoptosis. Our results show that cellular effects of DETC are partially
      attributable to the initial redox cellular state, since the increase of GSH level
      by NAC pre-treatment prevented the observed changes.

PMID- 22872141
TI  - The impact of FANCD2 deficiency on formaldehyde-induced toxicity in human
      lymphoblastoid cell lines.
AB  - Formaldehyde (FA), a major industrial chemical and ubiquitous environmental
      pollutant, has recently been classified by the International Agency for Research
      on Cancer as a human leukemogen. The major mode of action of FA is thought to be
      the formation of DNA-protein cross-links (DPCs). Repair of DPCs may be mediated
      by the Fanconi anemia pathway; however, data supporting the involvement of this
      pathway are limited, particularly in human hematopoietic cells. Therefore, we
      assessed the role of FANCD2, a critical component of the Fanconi anemia pathway,
      in FA-induced toxicity in human lymphoblast cell models of FANCD2 deficiency
      (PD20 cells) and FANCD2 sufficiency (PD20-D2 cells). After treatment of the cells
      with 0-150 MUM FA for 24 h, DPCs were increased in a dose-dependent manner in
      both cell lines, with greater increases in FANCD2-deficient PD20 cells. FA also
      induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a
      dose-dependent manner in both cell lines, with greater increases in cytotoxicity
      and apoptosis in PD20 cells. Increased levels of gamma-ATR and gamma-H2AX in both
      cell lines suggested the recognition of FA-induced DNA damage; however, the
      induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially
      reducing the capacity to repair DPCs. Together, these findings suggest that
      FANCD2 protein and the Fanconi anemia pathway are essential to protect human
      lymphoblastoid cells against FA toxicity. Future studies are needed to delineate
      the role of this pathway in mitigating FA-induced toxicity, particularly in
      hematopoietic stem cells, the target cells in leukemia.

PMID- 22872142
TI  - Genotoxic damage in the oral mucosa cells of subjects carrying restorative dental
      fillings.
AB  - A large proportion of the population carries restorative dental fillings
      containing either classic Hg-based amalgams and/or the more frequently used
      methacrylates. Both Hg- and resin-based materials have been shown to be released
      into the buccal cavity and to be spread systemically. In addition, they induce
      toxic and genotoxic alterations in experimental test systems. Using the comet
      assay, we previously demonstrated that circulating lymphocytes of subjects with
      dental fillings have an increased DNA damage. Here, we analyzed the oral mucosa
      cells of 63 young subjects of both genders, by using both the comet assay and the
      micronucleus (MN) test and by monitoring cell death markers. The results obtained
      show that both amalgams and resin-based composite fillings can induce genotoxic
      damage in human oral mucosa cells, as convincingly and dose-dependently inferred
      from the results of the MN test and, more marginally, from comet assay data.
      Lifestyle variables, also including alcohol intake and smoking habits, did not
      affect the genotoxic response and did not act as confounding factors. Thus, we
      provide unequivocal evidence for the genotoxicity of both amalgams and resin
      based dental fillings in humans not only by testing circulating lymphocytes but
      also by analyzing oral mucosa cells. These findings are of particular relevance
      due to the circumstance that subjects with restorative materials are exposed
      continuously and for long periods of time.

PMID- 22872143
TI  - Clinical scores to predict recurrence risk of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common and chronic disease with a considerable
      risk of recurrence. Patients with unprovoked (in the absence of a transient risk
      factor) VTE have a recurrence risk as high as 30% within five years after
      cessation of anticoagulation. Depending on patient selection the case-fatality
      rate of recurrence ranges between 3.6%-10%. Thus, indefinite anticoagulation
      treatment should be considered in these patients. However, anticoagulation
      confers a considerable risk of bleeding (fatal bleedings 0.1%-0.5%/year). It is
      therefore of utmost clinical importance to identify those patients, who will not
      benefit from indefinite anticoagulation, i.e. patients, in whom the bleeding risk
      during anticoagulant treatment is higher than the risk of recurrence. Several
      attempts to discriminate patients with a high from those with a low risk of
      recurrence including screening for acquired and inherited thrombotic risk factors
      or measurement of coagulation activation markers have either failed
      (thrombophilia screening) or were of moderate success (stratification according
      to D-dimer only). A novel approach for assessing risk of recurrent VTE consists
      of linking clinical patient characteristics with laboratory testing. Several such
      scoring models which can be used to assess the risk of recurrent VTE have been
      developed and await prospective validation before they can be applied in daily
      routine care. The aim of this report is to describe currently available scoring
      systems in more detail.

PMID- 22872144
TI  - Three-dimensional cell culture model for measuring the effects of interstitial
      fluid flow on tumor cell invasion.
AB  - The growth and progression of most solid tumors depend on the initial
      transformation of the cancer cells and their response to stroma-associated
      signaling in the tumor microenvironment (1). Previously, research on the tumor
      microenvironment has focused primarily on tumor-stromal interactions (1-2).
      However, the tumor microenvironment also includes a variety of biophysical
      forces, whose effects remain poorly understood. These forces are biomechanical
      consequences of tumor growth that lead to changes in gene expression, cell
      division, differentiation and invasion(3). Matrix density (4), stiffness (5-6),
      and structure (6-7), interstitial fluid pressure (8), and interstitial fluid flow
      (8) are all altered during cancer progression. Interstitial fluid flow in
      particular is higher in tumors compared to normal tissues (8-10). The estimated
      interstitial fluid flow velocities were measured and found to be in the range of
      0.1-3 MUm s(-1), depending on tumor size and differentiation (9, 11). This is due
      to elevated interstitial fluid pressure caused by tumor-induced angiogenesis and
      increased vascular permeability (12). Interstitial fluid flow has been shown to
      increase invasion of cancer cells (13-14), vascular fibroblasts and smooth muscle
      cells (15). This invasion may be due to autologous chemotactic gradients created
      around cells in 3-D (16) or increased matrix metalloproteinase (MMP) expression
      (15), chemokine secretion and cell adhesion molecule expression (17). However,
      the mechanism by which cells sense fluid flow is not well understood. In addition
      to altering tumor cell behavior, interstitial fluid flow modulates the activity
      of other cells in the tumor microenvironment. It is associated with (a) driving
      differentiation of fibroblasts into tumor-promoting myofibroblasts (18), (b)
      transporting of antigens and other soluble factors to lymph nodes (19), and (c)
      modulating lymphatic endothelial cell morphogenesis (20). The technique presented
      here imposes interstitial fluid flow on cells in vitro and quantifies its effects
      on invasion (Figure 1). This method has been published in multiple studies to
      measure the effects of fluid flow on stromal and cancer cell invasion (13-15,
      17). By changing the matrix composition, cell type, and cell concentration, this
      method can be applied to other diseases and physiological systems to study the
      effects of interstitial flow on cellular processes such as invasion,
      differentiation, proliferation, and gene expression.

PMID- 22872145
TI  - First-trimester cystic hygroma:  relationship of nuchal translucency thickness
      and outcomes.
AB  - OBJECTIVE: To estimate the relationship between nuchal translucency thickness and
      abnormal karyotype, major congenital anomaly, perinatal loss, and composite
      abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. METHODS:
      We performed a retrospective cohort study of first-trimester fetuses with
      ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period.
      RESULTS: There were 944 first-trimester fetuses with nuchal cystic hygroma. A
      karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major
      congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal
      karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively
      terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of
      fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal
      translucency thickness increased the odds of an abnormal karyotype by 44%
      (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29-1.60, P<.001),
      the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08-1.47,
      P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07-2.02,
      P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77,
      95% CI 1.15-2.74, P=.01). CONCLUSION: First-trimester nuchal cystic hygroma is
      associated with high rates of karyotype abnormality, major congenital anomaly,
      perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency
      increases, the odds of abnormal karyotype, major congenital anomaly, perinatal
      loss, and abnormal outcome increase.

PMID- 22872146
TI  - Immediate compared with delayed pushing in the second stage of labor: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate whether immediate or delayed pushing in the second stage
      of labor optimizes spontaneous vaginal delivery and other perinatal outcomes.
      DATA SOURCES: We searched electronic databases MEDLINE and CINHAL through August
      2011 without restrictions. The search terms used were MeSH headings, text words,
      and word variations of the words or phrases labor, laboring down, passive
      descent, passive second stage, physiologic second stage, spontaneous pushing,
      pushing, or bearing down. METHODS OF STUDY SELECTION: We searched for randomized
      controlled trials comparing immediate with delayed pushing in the second stage of
      labor. The primary outcome was spontaneous vaginal delivery. Secondary outcomes
      were instrumental delivery, cesarean delivery, duration of the second stage,
      duration of active pushing, and other maternal and neonatal outcomes.
      Heterogeneity was assessed using the Q test and I2. Pooled relative risks (RRs)
      and weighted mean differences were calculated using random-effects models.
      TABULATION, INTEGRATION, AND RESULTS: Twelve randomized controlled trials (1,584
      immediate and 1,531 delayed pushing) met inclusion criteria. Overall, delayed
      pushing was associated with an increased rate of spontaneous vaginal delivery
      compared with immediate pushing (61.5% compared with 56.9%, pooled RR 1.09, 95%
      confidence interval [CI] 1.03-1.15). This increase was smaller and not
      statistically significant among high-quality studies (59.0% compared with 54.9%,
      pooled RR 1.07, 95% CI 0.98-1.26) but larger and statistically significant in
      lower-quality studies (81.0% compared with 71.0%%, pooled RR 1.13, 95% CI 1.02
      1.24). Operative vaginal delivery rates were high in most studies and not
      significantly different between the two groups (33.7% compared with 37.4%, pooled
      RR 0.89, 95% CI 0.76-1.06). Delayed pushing was associated with prolongation of
      the second stage (weighted mean difference 56.92 minutes, 95% CI 42.19-71.64) and
      shortened duration of active pushing (weighted mean difference -21.98 minutes,
      95% CI -31.29 to -12.68). CONCLUSION: Studies to date suggest there are few
      clinical differences in outcomes with immediate compared with delayed pushing in
      the second stage of labor, especially when high-quality studies are pooled.
      Effects on maternal and neonatal outcomes remain uncertain.

PMID- 22872149
TI  - Fanconi proteins get histones moving.

PMID- 22872147
TI  - Genetic control of multiple births in low ovulating mammalian species.
AB  - In mammals, litter size is a highly variable trait. Some species such as humans
      or cattle are monotocous, with one or sometimes two newborns per birth, whereas
      others, the polytocous species such as mice or pigs, are highly prolific and
      often produce a dozen newborns at each farrowing. In monotocous species, however,
      two or three newborns per birth may sometime be unwanted. In more polytocous
      species such as sheep or pigs, litter size is studied in order to increase
      livestock prolificacy. By contrast, twinning rates in humans or cattle may
      increase birth difficulties and health problems in the newborns. In this context,
      the aim of our review was to provide a clearer understanding of the genetic and
      physiological factors that control multiple births in low-ovulating mammalian
      species, with particular focus on three species: sheep, cattle, and humans, where
      knowledge of the ovulation rate in one may enlighten findings in the others. This
      article therefore reviews the phenotypic and genetic variability observed with
      respect to ovulation and twinning rates. It then presents the QTL and major genes
      that have been identified in each species. Finally, we draw a picture of the
      diversity of the physiological mechanisms underlying multiple ovulation. Although
      several major genes have been discovered in sheep, QTL detection methods in
      humans or cattle have suggested that the determinism of litter size is complex
      and probably involves several genes in order to explain variations in the number
      of ovulations.

PMID- 22872148
TI  - The Mitotic Exit Network and Cdc14 phosphatase initiate cytokinesis by
      counteracting CDK phosphorylations and blocking polarised growth.
AB  - Polarisation of the actin cytoskeleton must cease during cytokinesis, to support
      efficient assembly and contraction of the actomyosin ring at the site of cell
      division, but the underlying mechanisms are still understood poorly in most
      species. In budding yeast, the Mitotic Exit Network (MEN) releases Cdc14
      phosphatase from the nucleolus during anaphase, leading to the inactivation of
      mitotic forms of cyclin-dependent kinase (CDK) and the onset of septation, before
      G1-CDK can be reactivated and drive re-polarisation of the actin cytoskeleton to
      a new bud. Here, we show that premature inactivation of mitotic CDK, before
      release of Cdc14, allows G1-CDK to divert the actin cytoskeleton away from the
      actomyosin ring to a new site of polarised growth, thereby delaying progression
      through cytokinesis. Our data indicate that cells normally avoid this problem via
      the MEN-dependent release of Cdc14, which counteracts all classes of CDK-mediated
      phosphorylations during cytokinesis and blocks polarised growth. The
      dephosphorylation of CDK targets is therefore central to the mechanism by which
      the MEN and Cdc14 initiate cytokinesis and block polarised growth during late
      mitosis.

PMID- 22872150
TI  - DEAD-box protein DDX3 associates with eIF4F to promote translation of selected
      mRNAs.
AB  - Here, we have characterized a step in translation initiation of viral and
      cellular mRNAs that contain RNA secondary structures immediately at the vicinity
      of their m(7)GTP cap. This is mediated by the DEAD-box helicase DDX3 which can
      directly bind to the 5' of the target mRNA where it clamps the entry of eIF4F
      through an eIF4G and Poly A-binding protein cytoplasmic 1 (PABP) double
      interaction. This could induce limited local strand separation of the secondary
      structure to allow 43S pre-initiation complex attachment to the 5' free extremity
      of the mRNA. We further demonstrate that the requirement for DDX3 is highly
      specific to some selected transcripts, cannot be replaced or substituted by eIF4A
      and is only needed in the very early steps of ribosome binding and prior to 43S
      ribosomal scanning. Altogether, these data define an unprecedented role for a
      DEAD-box RNA helicase in translation initiation.

PMID- 22872151
TI  - A high-density consensus map of A and B wheat genomes.
AB  - A durum wheat consensus linkage map was developed by combining segregation data
      from six mapping populations. All of the crosses were derived from durum wheat
      cultivars, except for one accession of T. ssp. dicoccoides. The consensus map was
      composed of 1,898 loci arranged into 27 linkage groups covering all 14
      chromosomes. The length of the integrated map and the average marker distance
      were 3,058.6 and 1.6 cM, respectively. The order of the loci was generally in
      agreement with respect to the individual maps and with previously published maps.
      When the consensus map was aligned to the deletion bin map, 493 markers were
      assigned to specific bins. Segregation distortion was found across many durum
      wheat chromosomes, with a higher frequency for the B genome. This high-density
      consensus map allowed the scanning of the genome for chromosomal rearrangements
      occurring during the wheat evolution. Translocations and inversions that were
      already known in literature were confirmed, and new putative rearrangements are
      proposed. The consensus map herein described provides a more complete coverage of
      the durum wheat genome compared with previously developed maps. It also
      represents a step forward in durum wheat genomics and an essential tool for
      further research and studies on evolution of the wheat genome.

PMID- 22872152
TI  - TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries.
AB  - RATIONALE: Pressure-induced arterial depolarization and constriction (the
      myogenic response) is a smooth muscle cell (myocyte)-specific mechanism that
      controls regional organ blood flow and systemic blood pressure. Several different
      nonselective cation channels contribute to pressure-induced depolarization, but
      signaling mechanisms involved are unclear. Similarly uncertain is the
      contribution of anion channels to the myogenic response and physiological
      functions and mechanisms of regulation of recently discovered transmembrane 16A
      (TMEM16A), also termed Anoctamin 1, chloride (Cl(-)) channels in arterial
      myocytes. OBJECTIVE: To investigate the hypothesis that myocyte TMEM16A channels
      control membrane potential and contractility and contribute to the myogenic
      response in cerebral arteries. METHODS AND RESULTS: Cell swelling induced by
      hyposmotic bath solution stimulated Cl(-) currents in arterial myocytes that were
      blocked by TMEM16A channel inhibitory antibodies, RNAi-mediated selective TMEM16A
      channel knockdown, removal of extracellular calcium (Ca(2+)), replacement of
      intracellular EGTA with BAPTA, a fast Ca(2+) chelator, and Gd(3+) and SKF-96365,
      nonselective cation channel blockers. In contrast, nimodipine, a voltage
      dependent Ca(2+) channel inhibitor, or thapsigargin, which depletes intracellular
      Ca(2+) stores, did not alter swelling-activated TMEM16A currents. Pressure
      induced (-40 mm Hg) membrane stretch activated ion channels in arterial myocyte
      cell-attached patches that were inhibited by TMEM16A antibodies and were of
      similar amplitude to recombinant TMEM16A channels. TMEM16A knockdown reduced
      intravascular pressure-induced depolarization and vasoconstriction but did not
      alter depolarization-induced (60 mmol/L K(+)) vasoconstriction. CONCLUSIONS:
      Membrane stretch activates arterial myocyte TMEM16A channels, leading to membrane
      depolarization and vasoconstriction. Data also provide a mechanism by which a
      local Ca(2+) signal generated by nonselective cation channels stimulates TMEM16A
      channels to induce myogenic constriction.

PMID- 22872153
TI  - A Nodal-to-TGFbeta cascade exerts biphasic control over cardiopoiesis.
AB  - RATIONALE: The transforming growth factor-beta (TGFbeta) family member Nodal
      promotes cardiogenesis, but the mechanism is unclear despite the relevance of
      TGFbeta family proteins for myocardial remodeling and regeneration. OBJECTIVE: To
      determine the function(s) of TGFbeta family members during stem cell
      cardiogenesis. METHODS AND RESULTS: Murine embryonic stem cells were engineered
      with a constitutively active human type I Nodal receptor (caACVR1b) to mimic
      activation by Nodal and found to secrete a paracrine signal that promotes
      cardiogenesis. Transcriptome and gain- and loss-of-function studies identified
      the factor as TGFbeta2. Both Nodal and TGFbeta induced early cardiogenic
      progenitors in embryonic stem cell cultures at day 0 to 2 of differentiation.
      However, Nodal expression declines by day 4 due to feedback inhibition, whereas
      TGFbeta persists. At later stages (days 4-6), TGFbeta suppresses the formation of
      cardiomyocytes from multipotent Kdr(+) progenitors while promoting the
      differentiation of vascular smooth muscle and endothelial cells. CONCLUSIONS:
      Nodal induces TGFbeta, and both stimulate the formation of multipotent
      cardiovascular Kdr(+) progenitors. TGFbeta, however, becomes uniquely responsible
      for controlling subsequent lineage segregation by stimulating vascular smooth
      muscle and endothelial lineages and simultaneously blocking cardiomyocyte
      differentiation.

PMID- 22872154
TI  - Ces3/TGH deficiency improves dyslipidemia and reduces atherosclerosis in Ldlr(-/
      ) mice.
AB  - RATIONALE: Carboxylesterase 3/triacylglycerol hydrolase (TGH) has been shown to
      participate in hepatic very low-density lipoprotein (VLDL) assembly. Deficiency
      of TGH in mice lowers plasma lipids and atherogenic lipoproteins without inducing
      hepatic steatosis. OBJECTIVE: To investigate the contribution of TGH to
      atherosclerotic lesion development in mice that lack low-density lipoprotein
      receptor (LDLR). METHODS AND RESULTS: Mice deficient in LDL receptor (Ldlr(-/-))
      and mice lacking both TGH and LDLR (Tgh(-/-)/Ldlr(-/-)) were fed with a Western
      type diet for 12 weeks. Analysis of Tgh(-/-)/Ldlr(-/-) plasma showed an
      atheroprotective lipoprotein profile with decreased cholesterol in the VLDL and
      the LDL fractions, concomitant with elevated high-density lipoprotein
      cholesterol. Significantly reduced plasma apolipoprotein B levels were also
      observed in Tgh(-/-)/Ldlr(-/-) mice. Consequently, Tgh(-/-)/Ldlr(-/-) mice
      presented with a significant reduction (54%, P<0.01) of the high-fat, high
      cholesterol dieteninduced atherosclerotic plaques when compared with
      Tgh(+/+)/Ldlr(-/-) mice in the cross-sectional aortic root analysis. TGH
      deficiency did not further increase liver steatosis despite lowering plasma
      lipids, mainly due to reduced hepatic lipogenesis. The ameliorated dyslipidemia
      in Tgh(-/-)/Ldlr(-/-) mice was accompanied with significantly improved insulin
      sensitivity. CONCLUSIONS: Inhibition of TGH activity ameliorates atherosclerosis
      development and improves insulin sensitivity in Ldlr(-/-) mice.

PMID- 22872155
TI  - Direct electroplating of copper on tantalum from ionic liquids in high vacuum:
      origin of the tantalum oxide layer.
AB  - In this paper, it is shown that high vacuum conditions are not sufficient to
      completely remove water and oxygen from the ionic liquid 1-ethyl-3
      methylimidazolium chloride. Complete removal of water demands heating above 150 
      degrees C under reduced pressure, as proven by Nuclear Reaction Analysis (NRA).
      Dissolved oxygen gas can only be removed by the use of an oxygen scavenger such
      as hydroquinone, despite the fact that calculations show that oxygen should be
      removed completely by the applied vacuum conditions. After applying a strict
      drying procedure and scavenging of molecular oxygen, it was possible to deposit
      copper directly on tantalum without the presence of an intervening oxide layer.

PMID- 22872156
TI  - Genetic variants that affect platelet function.
AB  - PURPOSE OF REVIEW: This review summarizes our current knowledge of common gene
      variants (polymorphisms) that have small individual effects on platelet function
      in humans, but can cumulatively lead to hyperreactive platelets and increase risk
      for negative outcomes in thrombotic disorders. RECENT FINDINGS: Candidate gene
      association and genome-wide association studies (GWAS) have identified loci that
      include single nucleotide polymorphisms, which exert a cumulative effect on
      platelet function by modifying basic platelet parameters, such as mean platelet
      volume (MPV) or platelet count, by altering the expression or activity of key
      platelet receptors, or by influencing downstream effector pathways utilized by
      these receptors. SUMMARY: Variation in MPV between normal individuals is
      responsible for roughly a two-fold range in platelet protein content, including
      key surface receptors and reactive granule constituents, the association of
      ADRA2, GP1BA, GP6, ITGA2 and P2Y12 variants with platelet reactivity, initially
      identified by candidate gene analyses, has now been validated by genome-wide
      approaches in much larger individual cohorts, and GWAS have identified novel gene
      variants, most notably PEAR1, that participate in variation in platelet
      reactivity among normal individuals, all of which contribute to a genetic basis
      for differences in platelet reactivty among normal individuals.

PMID- 22872157
TI  - Thrombopoietin-receptor agonists.
AB  - PURPOSE OF REVIEW: Thrombopoietin-receptor agonists (TPO-RAs) have been approved
      for use in immune thrombocytopenia (ITP) after showing safety and efficacy. There
      is increasing interest to expand the role of TPO-RAs, both in ITP as well as in
      other thrombocytopenic disorders. RECENT FINDINGS: In ITP, more studies are
      providing evidence of TPO-RA efficacy and safety, as well as their applicability
      to various patient groups, including children. Use of TPO-RAs in hepatitis C has
      shown early success in allowing treatments in patients who would otherwise be
      excluded due to thrombocytopenia. Use in congenital thrombocytopenias has also
      shown early success. The use of TPO-RAs in myelodysplastic syndrome (MDS) is
      questionable after reports of increasing blasts and leukemic transformation,
      whereas in other chemotherapy-induced thrombocytopenias (C-ITs) reports are few.
      Bone marrow fibrosis remains an area of active study, although the data to date
      suggest this is seen in a small minority of patients, and is reversible and of
      questionable clinical relevance. Thrombotic complications are also an area of
      concern and need further close follow-up. SUMMARY: The use of TPO-RAs continues
      to grow as more evidence of safety and efficacy is found. More studies are needed
      to determine their utility in other diseases as well as to better characterize
      adverse events observed to date.

PMID- 22872159
TI  - Electronic and vibrational circular dichroism spectroscopies for the
      understanding of chiral organization in porphyrin aggregates.
AB  - Dichroic optical spectroscopies and theoretical modelling have been used to
      describe the structure of aggregates of porphyrins in their gels in terms of: (i)
      the formation of helicoidal structures, (ii) the sign of the handedness, (iii)
      their extent and degree of structural order, and (iv) the annealing of the
      structural defects.

PMID- 22872158
TI  - Rare factor deficiencies.
AB  - PURPOSE OF REVIEW: By definition, rare factor deficiencies have a prevalence of
      less than 200,000 in the US population, or an incidence of less than one in 2000
      in Europe. The very small numbers of patients with rare disorders present
      challenges in diagnosis, evaluation of bleeding risk and treatment. Use of new
      assays, full genome sequencing, and global clotting assays will significantly
      improve diagnosis of patients with rare bleeding disorders. RECENT FINDINGS: In
      addition to new assays available for monitoring patients, new therapy, both
      recombinant and plasma derived, is now available. Registries and clinical trials
      have demonstrated decreased bleeding and improved outcomes when patients are
      treated with these agents. Expanding international registries have been initiated
      to correlate genotype and bleeding phenotype in conjunction with global assays.
      SUMMARY: Ongoing research continues to expand our understanding of the
      pathophysiology of rare factor deficiencies. This work complements medical
      practice to incorporate early diagnosis and new treatment options for patients,
      resulting in safer and less sensitizing regimens and much improved clinical
      outcomes.

PMID- 22872160
TI  - Comparison study of temporal regularization methods for fully 5D reconstruction
      of cardiac gated dynamic SPECT.
AB  - Temporal regularization plays a critical role in cardiac gated dynamic SPECT
      reconstruction, of which the goal is to obtain an image sequence from a single
      acquisition which simultaneously shows both cardiac motion and tracer
      distribution change over the course of imaging (termed 5D). In our recent work,
      we explored two different approaches for temporal regularization of the dynamic
      activities in gated dynamic reconstruction without the use of fast camera
      rotation: one is the dynamic EM (dEM) approach which is imposed on the temporal
      trend of the time activity of each voxel, and the other is a B-spline modeling
      approach in which the time activity is regulated by a set of B-spline basis
      functions. In this work, we extend the B-spline approach to fully 5D
      reconstruction and conduct a thorough quantitative comparison with the dEM
      approach. In the evaluation of the reconstruction results, we apply a number of
      quantitative measures on two major aspects of the reconstructed dynamic images:
      (1) the accuracy of the reconstructed activity distribution in the myocardium and
      (2) the ability of the reconstructed dynamic activities to differentiate
      perfusion defects from normal myocardial wall uptake. These measures include the
      mean square error (MSE), bias-variance analysis, accuracy of time-activity curves
      (TAC), contrast-to-noise ratio of a defect, composite kinetic map of the left
      ventricle wall and perfusion defect detectability with channelized Hotelling
      observer. In experiments, we simulated cardiac gated imaging with the NURBS-based
      cardiac-torso phantom and Tc99m-Teboroxime as the imaging agent, where
      acquisition with the equivalent of only three full camera rotations was used
      during the imaging period. The results show that both dEM and B-spline 5D could
      achieve similar overall accuracy in the myocardium in terms of MSE. However,
      compared to dEM 5D, the B-spline approach could achieve a more accurate
      reconstruction of the voxel TACs; in particular, B-spline 5D could achieve a much
      smaller bias level in the early uptake stage of the imaging period. Furthermore,
      it could allow better separation of the perfusion defect from the normal at both
      the early and the late stages of the imaging period.

PMID- 22872162
TI  - Serotonin transporter genotype 5HTTLPR as a marker of differential
      susceptibility? A meta-analysis of child and adolescent gene-by-environment
      studies.
AB  - We present results of a meta-analysis of gene-by-environment (G * E) studies
      involving the serotonin transporter genotype 5HTTLPR to evaluate empirical
      support for two competing conceptual frameworks in developmental psychopathology:
      diathesis-stress and differential susceptibility. From a diathesis-stress
      perspective, the cumulative negative effects of the short allele (ss and sl
      genotypes) and adverse environments on development have been stressed. From a
      differential-susceptibility perspective, carriers of the s allele are predicted
      to be more open to adverse as well as positive environments, for better and for
      worse. Studies with children and adolescents up to 18 years of age (N=9361) were
      included. We found 41 effect sizes (N=5863) for the association between negative
      environments and developmental outcomes with or without significant moderation by
      5HTTLPR genotype and 36 effect sizes (N=3498) for the potentially 5HTTLPR
      moderated association between positive environments and developmental outcomes.
      Five moderators were examined: age, ethnicity, genotyping (biallelic or
      triallelic) and methods used to assess environment and outcome. In the total set
      of studies, including studies with mixed ethnicities, we found that ss/sl
      carriers were significantly more vulnerable to negative environments than ll
      carriers, thus supporting the diathesis-stress model. In the Caucasian samples,
      however, ss/sl carriers also profited significantly more from positive
      environmental input than ll carriers. Associations between (positive or negative)
      environment and (positive or negative) developmental outcome were absent for ll
      carriers. The meta-analytic findings support the hypothesis that in Caucasian
      samples 5HTTLPR is a genetic marker of differential susceptibility. G * E
      interactions might be critically dependent on ethnicity.

PMID- 22872161
TI  - Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like
      phenotypes in a mouse model of 22q11 deletion syndrome.
AB  - The 22q11.2 microdeletion is one of the highest genetic risk factors for
      schizophrenia. It is not well understood which interactions of deleted genes in
      22q11.2 regions are responsible for the pathogenesis of schizophrenia, but
      catechol-O-methytransferase (COMT) is among the candidates. Df1/+ mice are
      22q11.2 deletion syndrome (22q11DS) model mice with a hemizygous deletion of 18
      genes in the 22q11-related region. Df1/+ mice showed enhanced response to the
      dopamine D1 agonist, SKF38393, and the N-methyl-D-aspartate antagonist, MK801,
      which can be normalized by a GABA(A) receptor agonist, bretazenil, or a GABA(A)
      alpha2/alpha3 receptor agonist, SL651498. Here, we demonstrated the curing
      effects of virus-mediated reintroduction of Comt to the prefrontal cortex (PFC)
      in Df1/+ mice. In contrast, both Comt overexpression and Comt inhibition caused
      an abnormal responsiveness to Bretazenil, a GABA(A) receptor agonist in control
      mice. Comt overexpression increased MK801-induced interneuronal activation and
      GABA release in the PFC. The expression levels of GABA-related genes such as
      Gabrb2 (GABA(A)receptor beta2), Gad2 (glutamic acid decarboxylase 65 (Gad65)) and
      Reln (Reelin) correlate with a Comt expression level in PFC. Our data suggest
      that Comt-mediated regulation of GABAergic system might be involved in the
      behavioral pathogenesis of Df1/+ mice.

PMID- 22872163
TI  - Inhibin B and anti-Mullerian hormone/Mullerian-inhibiting substance may
      contribute to the male bias in autism.
AB  - The autistic spectrum disorders have a significant male bias in incidence, which
      is unexplained. The Sertoli cells of the immature testes secrete supra-adult
      levels of Mullerian-inhibiting substance/anti-Mullerian hormone (AMH) and inhibin
      B (InhB), with both hormones being putative regulators of brain development. We
      report here, that 82 boys with an autism spectrum disorder have normal levels of
      InhB and AMH. However, the boys' level of InhB correlated with their autism
      diagnostic interview-revised (ADI-R) scores for the social interaction (R=0.29,
      P=0.009, N=82) and communication domains (R=0.29, P=0.022, N=63), and with the
      number of autistic traits the boys exhibited (R=0.34 and 0.27, respectively). The
      strengths of the abovementioned correlates were stronger in the boys with milder
      autism (R=0.42 and 0.50, respectively), with AMH exhibiting a significant
      negative correlation to the ADI-R score in these boys (R=-0.44 and R=-0.39,
      respectively). Neither hormone correlated to the incidence of stereotyped and
      repetitive behaviours. This suggests that the male bias in the autistic spectrum
      has multiple determinants, which modulate the effects of an otherwise non
      dimorphic pathology. Furthermore, AMH and InhB have opposing effects on the
      SMAD1/5/8 pathway, and opposing correlates to autistic traits, implicating the
      SMAD pathways as a putative point of molecular convergence for the autistic
      spectrum.

PMID- 22872164
TI  - Aspirin decreases the risk of depression in older men with high plasma
      homocysteine.
AB  - High total plasma homocysteine (tHcy) is associated with increased risk of
      cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12)
      reduces tHcy by about 15%, but has equivocal effects on these health outcomes,
      suggesting that this relationship is either not causal or is confounded by other
      factors. The results of recent randomized trials suggest that antiplatelet
      therapy may confound these associations. This cross-sectional study assessed 3687
      men aged 69-87 years for history of clinically significant depression (Geriatric
      Depression Scale 15 items ?7) or a recorded diagnosis of depression in the
      Western Australian Data Linkage System, and collected information on the use of
      aspirin, B-vitamins and antidepressant medication, along with age, education,
      living arrangements, smoking history and medical comorbidity as assessed by the
      Charlson index. Participants donated a blood sample for the measurement of tHcy,
      and concentrations?15 MUmol l(-1) were considered high. Five hundred and thirteen
      (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy,
      41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic
      regression showed that high tHcy was associated with increased odds of depression
      (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20-2.14), as was the use of
      B-vitamins (OR=1.95, 95% CI=1.21-3.13). There was a significant interaction
      between high tHcy and aspirin use (OR=0.57, 95% CI=0.36-0.91), but not between
      high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26-2.46). The analyses were
      adjusted for smoking status, Charlson index and use of antidepressants. The
      results of this study indicate that older men with high tHcy who use aspirin have
      lower risk of depression, and suggest that antiplatelet therapy may be an
      effective preventive or management strategy for these cases. Randomized trials
      are required to confirm the antidepressant effect of aspirin in people with high
      tHcy.

PMID- 22872165
TI  - Grasping multiple sclerosis: do quantitative motor assessments provide a link
      between structure and function?
AB  - Motor disability in MS is commonly assessed by the Expanded Disability Status
      Scale (EDSS). Categorical rating scales are limited by subjective error and inter
      rater variability. Therefore, objective and quantitative measures of motor
      disability may be useful to supplement the EDSS in the setting of clinical
      trials. It was previously shown that grip-force-variability (GFV) is increased in
      MS. We hypothesized that GFV may be an objective measure of motor disability in
      MS. To investigate whether the increase in GFV in MS is correlated to the
      clinical disability as assessed by the EDSS and to microstructural changes in the
      brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and
      lifting task in 27 MS patients and 23 controls using a grip-device equipped with
      a force transducer. The EDSS was assessed by neurologists experienced in MS.
      Patients underwent diffusion tensor imaging at 3T to assess the fractional
      anisotropy (FA) of the cerebral white matter as a measure of microstructural
      brain integrity. GFV was increased in MS and correlated to changes in the FA of
      white matter in the vicinity of the somatosensory and visual cortex. GFV also
      correlated with the EDSS. GFV may be a useful objective measure of motor
      dysfunction in MS linked to disability and structural changes in the brain. Our
      data suggests that GFV should be further explored as an objective measure of
      motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept
      studies.

PMID- 22872166
TI  - Functional tumor infiltrating TH1 and TH2 effectors in large early-stage cervical
      cancer are suppressed by regulatory T cells.
AB  - OBJECTIVE: Analysis of tumor-infiltrating lymphocytes (TILs) is one of the
      cornerstones for the understanding of immune responses prevailing in the tumor
      microenvironment. We studied TILs from squamous cell carcinoma of the cervix ex
      vivo without proliferating them in vitro before analysis. METHODS: Whereas TILs
      were magnetic activated cell separation enriched and flow sorted into CD4 CD25
      (regulatory T cells [Tregs]), CD4 CD25 (effector T cells [Teffs]) were directly
      purified by flow cytometry, and both these subsets were characterized
      phenotypically and functionally. Tissue sections were probed for interleukin 4
      (IL-4) and interferon gamma. RESULTS: Effector T cells constitutively expressed
      both interferon gamma and IL-4 prototypical cytokines of TH1 and TH2,
      respectively, and were able to proliferate and secrete higher quantities of both
      cytokines in response to anti-CD3/anti-CD28 and autologous tumor lysates. Only
      53% of cervical cancer Tregs were FOXP3, elaborated transforming growth factor
      beta1, and IL-10 and were able to inhibit both T helper subsets. CONCLUSIONS:
      Intratumoral Teffs represented functionally active subsets of both TH1 and TH2
      that were not anergic but were suppressed by multiple Treg subsets, which
      comprised FOXP3 + Tregs and Tregs secreting transforming growth factor beta1 and
      IL-10. These results imply that the microenvironment of cervical carcinomas
      harbored both TH1 and TH2 subsets of CD4 Teffs that were functionally active but
      were perhaps unable to perform because of the overpowering effect of Tregs.

PMID- 22872167
TI  - Predicting the coexistence of an endometrial adenocarcinoma in the presence of
      atypical complex hyperplasia: immunohistochemical analysis of endometrial
      samples.
AB  - OBJECTIVE: This study aimed to determine whether immunohistochemical markers in
      complex atypical endometrial hyperplasia could predict the presence of a
      concurrent endometrial carcinoma. METHODS: Endometrial biopsies of 39 patients
      with complex atypical hyperplasia were selected retrospectively between 1999 and
      2006. Only patients who underwent a hysterectomy were included. A coexisting
      endometrial carcinoma was present in 25 patients (64%). Immunohistochemical
      analysis was performed on formalin-fixed paraffin-embedded sections of the
      endometrial biopsies, using antibodies for MIB-1, beta-catenin, E-cadherin, p53,
      PTEN, CD44, HER2-neu, survivin, COX-2, tenascin, and bcl-2. To evaluate the
      potential utility of these markers, a prediction model was constructed. RESULTS:
      In the univariate analysis, expressions of both PTEN and HER2-neu were
      significantly different between the groups with and without a coexisting
      endometrial carcinoma (P < 0.05). Loss of PTEN staining was found in 13 (54%) and
      1 (7%) of the patients with and without a coexistent carcinoma, respectively
      (odds ratio, 16.55; 95% confidence interval [CI], 1.87-146.65). HER2-neu
      expression was found in only 2 (8.6%) and 6 (43%) patients with and without a
      coexistent carcinoma, respectively, and was excluded from further analysis
      because of its low expression. A prediction model containing PTEN expression only
      showed an area under the curve of 73.4% (95% CI, 57.3%-89.6%). After adding MIB-1
      and p53, discriminative power improved to 87.2% (95% CI, 75.1%-99.3%).
      CONCLUSIONS: This study showed that PTEN expression in complex endometrial
      hyperplasia is a promising factor for the prediction of the presence of a
      coexisting endometrial carcinoma, and prediction may even better when MIB-1 and
      p53 expressions are considered simultaneously.

PMID- 22872168
TI  - State of the science in ovarian cancer quality of life research: a systematic
      review.
AB  - INTRODUCTION: Health-related quality of life (HRQOL) has become an increasingly
      important focus of outcomes in cancer care with the movement toward more patient
      oriented research. Quality-of-life outcomes are important in ovarian cancer,
      which has not yet benefitted from improved survival outcomes as have other
      diseases. This study was designed to systematically assess and summarize HRQOL in
      ovarian cancer. METHODS: A systematic search strategy was initiated to identify
      published literature measuring HRQOL of women with a diagnosis of ovarian cancer
      (OC). Data were synthesized to evaluate HRQOL and patient-reported outcome data
      at various time points: before, during, and after chemotherapy. Data were pooled
      and summary statistics compared across published studies. Comparisons of means
      were conducted using analysis of variance. RESULTS: There were 170 publications
      meeting all eligibility criteria, representing 139 unique studies of patients
      with ovarian cancer, where QOL data were collected. Within this literature, more
      than 90 different patient-reported outcome (PRO) instruments were administered.
      The most common HRQOL instruments included the European Organisation for Research
      and Treatment of Cancer QLQ-C30 and the Functional Assessment of Cancer Therapy.
      Few studies alone demonstrated significant differences in QOL between the
      experimental and comparison arm or throughout the treatment period. Pooled data,
      however, show that baseline QOL may significantly improve, particularly after
      completion of chemotherapy treatment. DISCUSSION: Despite the increase in
      assessment and reporting of QOL in ovarian cancer research studies during the
      past 15 years, there remains little consistency in the types and format of data
      collected. There is a need to enhance the standardized collection and reporting
      of HRQOL data from research involving women with ovarian cancer so that research
      can build on the cumulative knowledge base to improve outcomes in this patient
      population.

PMID- 22872169
TI  - Adipose tissue-derived PAI-1: a molecular link for thrombo-inflammatory disease
      states?

PMID- 22872172
TI  - Visualization and genetic manipulation of dendrites and spines in the mouse
      cerebral cortex and hippocampus using in utero electroporation.
AB  - In utero electroporation (IUE) has become a powerful technique to study the
      development of different regions of the embryonic nervous system (1-5). To date
      this tool has been widely used to study the regulation of cellular proliferation,
      differentiation and neuronal migration especially in the developing cerebral
      cortex (6-8). Here we detail our protocol to electroporate in utero the cerebral
      cortex and the hippocampus and provide evidence that this approach can be used to
      study dendrites and spines in these two cerebral regions. Visualization and
      manipulation of neurons in primary cultures have contributed to a better
      understanding of the processes involved in dendrite, spine and synapse
      development. However neurons growing in vitro are not exposed to all the
      physiological cues that can affect dendrite and/or spine formation and
      maintenance during normal development. Our knowledge of dendrite and spine
      structures in vivo in wild-type or mutant mice comes mostly from observations
      using the Golgi-Cox method( 9). However, Golgi staining is considered to be
      unpredictable. Indeed, groups of nerve cells and fiber tracts are labeled
      randomly, with particular areas often appearing completely stained while adjacent
      areas are devoid of staining. Recent studies have shown that IUE of fluorescent
      constructs represents an attractive alternative method to study dendrites, spines
      as well as synapses in mutant / wild-type mice (10-11) (Figure 1A). Moreover in
      comparison to the generation of mouse knockouts, IUE represents a rapid approach
      to perform gain and loss of function studies in specific population of cells
      during a specific time window. In addition, IUE has been successfully used with
      inducible gene expression or inducible RNAi approaches to refine the temporal
      control over the expression of a gene or shRNA (12). These advantages of IUE have
      thus opened new dimensions to study the effect of gene expression/suppression on
      dendrites and spines not only in specific cerebral structures (Figure 1B) but
      also at a specific time point of development (Figure 1C). Finally, IUE provides a
      useful tool to identify functional interactions between genes involved in
      dendrite, spine and/or synapse development. Indeed, in contrast to other gene
      transfer methods such as virus, it is straightforward to combine multiple RNAi or
      transgenes in the same population of cells. In summary, IUE is a powerful method
      that has already contributed to the characterization of molecular mechanisms
      underlying brain function and disease and it should also be useful in the study
      of dendrites and spines.

PMID- 22872171
TI  - Vascular cognitive impairment and Alzheimer's disease: role of cerebral
      hypoperfusion and oxidative stress.
AB  - Cerebrovascular disease may lead to a wide range of cognitive changes, referred
      to collectively as vascular cognitive impairment. Stroke increases the risk of
      cognitive impairment and dementia, and may contribute to the progression of
      Alzheimer's disease (AD). Apart from clinical stroke itself, vascular risk
      factors are associated with the development of cognitive impairment and dementia.
      Animal models involving a temporary or permanent interruption of blood flow in
      the common carotid arteries develop nonprogressive cognitive impairment.
      Oxidative stress during cerebral hypoperfusion in animal models plays a key role
      in neuronal death and may thus contribute to the development of cognitive
      impairment in cerebrovascular disease. Genetic and pharmacological interventions
      to inhibit the major source of reactive oxygen species, nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase, are neuroprotective in experimental
      cerebral ischemia. Recent studies have demonstrated that inhibition of NADPH
      oxidase activity can mitigate cognitive impairment in rodent models of cerebral
      hypoperfusion. In this article, we review the evidence linking cognitive
      impairment and/or AD with NADPH oxidase-dependent oxidative stress, including the
      renin-angiotensin system.

PMID- 22872173
TI  - Radiographic evaluation of the tegmen in patients with superior semicircular
      canal dehiscence.
AB  - OBJECTIVE: To determine a radiographic association between superior semicircular
      canal dehiscence (SSCD) and tegmen dehiscence (TD). STUDY DESIGN: Retrospective
      case-control series. SETTING: Tertiary referral center. PATIENTS: Patients seen
      between 2003 and 2010 with radiographic SSCD were compared with cochlear implant
      recipient controls. INTERVENTION: The tegmen and superior semicircular canal were
      evaluated on computed tomographic temporal bone scans. MAIN OUTCOME MEASURE: If
      detected, the widest point of the SSCD was measured. The tegmen was graded on a 5
      point scale. After analysis, a radiographic TD was defined as any single area of
      absent tegmen greater than 5 mm, multiple areas of absent tegmen, or evidence of
      meningocele. Age, sex, and body mass index were also noted. RESULTS: Thirty-eight
      patients with SSCD and 41 cochlear implant controls were identified. Seventy-six
      percent (29/38) of patients with unilateral or bilateral SSCD had a radiographic
      TD on at least 1 side compared with 22% (9/41) of the comparison group. Ninety
      four percent (7/18) of patients with bilateral SSCD had a TD on at least 1 side.
      Patients with SSCD had a 10.2 times (p < 0.001) higher odds of having
      radiographic TD in either ear compared to the controls. Among patients with any
      SSCD, for every millimeter increase in the width of dehiscence, the relative risk
      for any TD increased more than 2-fold (odds ratio, 2.5; p = 0.019). Age, sex, and
      a body mass index greater than 30 did not confound the association between SSCD
      and TD. CONCLUSION: There is a strong radiologic association between SSCD and TD,
      suggesting a similar etiologic process. The tegmen should be carefully evaluated
      in patients with SSCD. We have also proposed a new system for radiographically
      grading the integrity of the tegmen.

PMID- 22872174
TI  - Correlations of inflammatory biomarkers with the onset and prognosis of
      idiopathic sudden sensorineural hearing loss.
AB  - HYPOTHESIS: We investigated whether inflammatory biomarkers and stress are
      involved in the pathophysiology of idiopathic sensorineural hearing loss (ISHL).
      STUDY DESIGN: Individual cohort study. SETTING: Two tertiary centers. PATIENTS:
      Forty-three ISHL and 10 non-ISHL patients seen in our ENT departments from 2004
      to 2010 within a week from the onset of new symptoms and without steroid
      administration before visiting our departments. INTERVENTION: Multiple audiologic
      evaluations, blood tests including leukocyte counts, natural killer cell activity
      (NKCA), interleukin 6 (IL-6), tumor necrosis factor, high-sensitivity CRP (hCRP),
      and the General Health Questionnaire were used to evaluate the systemic stress
      and inflammatory response. MAIN OUTCOME MEASURES: Correlations between biomarkers
      and ISHL severity and prognosis were evaluated by statistical analysis. RESULTS:
      In the ISHL patients, a neutrophil count above the reference range was associated
      with severe hearing loss and poor prognosis, and was accompanied by low NKCA and
      high IL-6. In the non-ISHL patients, these associations were not present. The
      abnormal neutrophil count was independent of preexisting vascular diseases. The
      abnormal counts responded to treatment and decreased into the reference range.
      CONCLUSION: Neutrophil counts above the reference range of a facility will be a
      useful indicator of poor prognosis of ISHL. Synchronism of different types of NF
      kappaB activation pathways could be required to cause severe ISHL. An NKCA
      decrease, an acute neutrophil count increase, and an IL-6 increase can induce NF
      kappaB activation in the cochlea and cause severe ISHL. Further epidemiologic
      surveys should be conducted to evaluate whether stressful life events increase
      the risk of severe ISHL onset.

PMID- 22872175
TI  - Vestibular system changes in sudden deafness with and without vertigo:  a human
      temporal bone study.
AB  - OBJECTIVE: To investigate the vestibular system changes in sudden deafness with
      vertigo (SDwV) and sudden deafness without vertigo (SDwoV) and the cause of
      persistent canal paresis (CP) in SDwV patients. STUDY DESIGN: Retrospective
      study. MATERIALS AND METHODS: Four temporal bones from the affected ear in 4
      patients with unilateral sudden deafness (SD), 2 SDwV and 2 SDwoV, were selected.
      Four contralateral temporal bones with normal-hearing ears were defined as the
      control. Morphologic findings of the labyrinth, the number of Scarpa's ganglion
      cells, and the density of vestibular hair cells were investigated in all temporal
      bones. Clinical data and the results of vestibular tests of 11 patients with
      unilateral SD, as a separate group, also were investigated. RESULTS: Atrophic
      change of the organ of Corti, tectorial membrane, and stria vascularis in
      cochlea, and deposits and atrophic otoconial membrane in vestibular sense organs
      were seen on affected ears more than control ears. The density of Type I hair
      cells seemed to decrease on the saccular macula and the posterior semicircular
      canal crista on affected ears, and there was no remarkable difference between
      SDwV and SDwoV. In 1 patient with SDwoV who died 10 months after the onset of SD,
      there were large amount of deposits on the cupula, the atrophied otoconial
      membrane was peeling off from the saccular macula, and the saccular membrane
      collapsed to the saccular macula in the affected ear. In the clinical data, all
      SDwV who were examined within 2 years from the onset had CP, and all SDwV had
      profound hearing loss. CONCLUSION: There is no remarkable difference between SDwV
      and SDwoV in the number of Scarpa's ganglion cells and the density of vestibular
      hair cells. The damage of the extracellular superstructure is seen in SD with or
      without vertigo. The damage of extracellular superstructure is potentially one of
      the causes of persistent CP in patients with SD.

PMID- 22872176
TI  - Finite element analysis of damage by cochlear implant electrode array's proximal
      section to the basilar membrane.
AB  - HYPOTHESIS: This study aims to examine the mechanism of damage to the basilar
      membrane caused by the proximal section of the cochlear implant electrode array.
      BACKGROUND: The electrode array has been found to severely damage the basilar
      membrane. Most previous studies on cochlear implant insertion damage largely
      focused on the injury by the front section (tip) of the electrode array to the
      membrane. Little attempt has been made to investigate the damage caused by the
      array's proximal section. METHODS: A computational model using the finite element
      method has been developed for assessing the likelihood of the damage based on two
      criteria: 1) frequency of contact between the proximal section of the electrode
      array and the upper wall of the scala tympani where the basilar membrane is
      located, and 2) magnitude of the associated shear stresses at the contact areas.
      The model has been validated and used for studying the effect of electrode
      array's stiffness properties on the damage. RESULTS: The proximal section of the
      contour array is most likely to hit the basilar membrane, compared with its
      previous versions (the straight array and the single wire electrode). In terms of
      shear stress magnitude, the proximal section of the contour array exerts higher
      stresses on the scala tympani's upper wall and, thus, is more likely to damage
      the basilar membrane, compared with that of the straight array. CONCLUSION:
      Results from this study are useful for cochlear implant surgeons in better
      understanding the mechanism of damage by the electrode array's proximal section
      to the basilar membrane and in establishing advanced insertion techniques for
      reducing the damage (in particular, the results strongly support the "advance off
      stylet" technique). The outcomes of the study also are beneficial for cochlear
      implant designers in selecting appropriate stiffness profiles for future
      electrode arrays, which are expected to cause minimal damage to the basilar
      membrane (a new design of the contour array with stiffness increasing from the
      front to the proximal section is highly recommended).

PMID- 22872177
TI  - Repetitive transcranial magnetic stimulation noise levels:  methodological
      implications for tinnitus treatment.
AB  - OBJECTIVE: To measure noise levels generated by repetitive transcranial magnetic
      stimulation. INTERVENTION: Repetitive transcranial magnetic stimulation (rTMS).
      MAIN OUTCOME MEASURES: rTMS noise levels measured in equivalent continuous sound
      level (LAeq) and in peak level (LC, peak), as a function of maximum power output
      of the equipment. METHODS: rTMS noise levels were measured for an active and a
      corresponding sham coil, as a function of distance and percentage power output of
      a MagPro X100 system (Medtronic) and compared with occupational noise exposure
      standards, using parameters classically used for rTMS tinnitus treatment.
      RESULTS: Significant differences in frequency composition and intensity levels
      were observed between sham and active coil noises. The active coil noise reached,
      at 50% power, 96 LAeq (peak at 132 LC, peak), varying by 3.9 LAeq (3.9 LC, peak)
      per 10% of power increase, whereas the sham coil reached 87 LAeq (114 LC, peak),
      varying by 3.2 LAeq (3.6 LC, peak) per 10% of power increase. CONCLUSION: rTMS
      noise levels differ significantly between active and sham coils, and can go
      beyond the American and European legal occupational noise limits, hence making
      ear protection a specific issue, particularly relevant to rTMS treatment for
      tinnitus.

PMID- 22872178
TI  - Minimal access surgery for implantable bone conduction systems: early experience
      with the "Sheffield" incision.
AB  - INTRODUCTION: To compare the results of the "Sheffield" incision technique for
      implantable temporal bone conduction systems against the previous inferiorly
      based flap technique. MATERIALS AND METHODS: Bone-Anchored Hearing Aid surgery
      performed over a 2-year period using the new incision (32 patients) was monitored
      prospectively. A short "lazy S" incision, within the hairline was used followed
      by soft tissue reduction and implantation. Age range was 6 to 76 years. Average
      follow-up was 6 months. The results in this group were compared with those of a
      similar group (20 patients) where the inferiorly based flap was used. RESULTS:
      The "Sheffield" incision produced more aesthetically pleasing flaps, and patient
      satisfaction was high. There were no major complications like flap necrosis or
      fixture loss (against 25% flap necrosis in the flap technique). One patient had a
      wound hematoma and subsequent wound dehiscence, which needed clearing and closure
      under anesthetic. Minor complications included granulations in 4 (13%) at the
      lower edges of the incision (55% in the flap technique), skin redness in 3 (9%)
      of Holgers Grade 2, and small wound dehiscence in 3 (3%), all of which settled
      conservatively. DISCUSSION: The results of the "Sheffield" incision compare well
      with other similar case series and with our own results from using the
      alternative inferior flap technique. In addition, it offers simplicity, speed,
      and aesthetically pleasing results with minimal postoperative management.

PMID- 22872179
TI  - Cochlear implant-evoked cortical activation in children with cochlear nerve
      deficiency.
AB  - OBJECTIVE: To report the results of cochlear implant-elicited cortical auditory
      evoked potentials (eCAEP) in children with cochlear nerve deficiency (CND). STUDY
      DESIGN: Case control series. SETTING: Tertiary academic referral center.
      PATIENTS: Seven children with CND that have a cochlear implant in their affected
      ear. Four children without CND served as controls. INTERVENTION(S): eCAEPs were
      elicited by activation of individual cochlear implant electrodes. MAIN OUTCOME
      MEASURE(S): Onset responses (P1-N1-P2 complex). RESULTS: Three of 7 CND children
      demonstrated eCAEP responses across a broad range of electrodes despite having
      limited or no open set speech perception abilities using their implants. Two of
      these children had eCAEPs that were characterized by substantial variability in
      latency, amplitude, and number of electrodes with identifiable responses. The
      remaining 4 ears with CND and poor speech perception had multiphasic responses
      that are inconsistent with eCAEPs. Non-CND ears with excellent speech perception
      abilities demonstrated robust responses on all electrodes stimulated. CONCLUSION:
      Abent eCAEP responses were indicative of poor open-set speech perception skills
      in all cases. However, eCAEP onset responses were measurable in some children
      with imaging evidence of CND, indicating probable cochlear nerve hypoplasia
      rather than aplasia. That some children with CND and poor speech perception had
      robust eCAEPs in some instances makes this particular measure of limited use for
      predicting good speech perception outcomes after cochlear implantation in these
      children. The origin of multiphasic responses remains to be determined but may be
      of somatosensory origin in some instances.

PMID- 22872180
TI  - Peripheral facial nerve palsy:  how effective is rehabilitation?
AB  - OBJECTIVE: To review the current literature to assess the effectiveness of
      rehabilitation treatment for peripheral facial nerve palsy. DATA SOURCES: A
      review of the literature was conducted using the following database: PubMed,
      EMBASE, PEDro, and Scopus. All randomized or quasi randomized controlled trials,
      case control, cohort studies and case series greater than 6 published between
      1990 and 2010 in the English language were included. STUDY SELECTION: All types
      of peripheral facial nerve palsy were included. We considered all the exercises
      or rehabilitation programs provided by a physiotherapy in outpatient or home
      setting and excluded trials in which a drug therapy or surgical intervention was
      investigated. Three reviewers independently selected the articles. DATA
      EXTRACTION: To rate the methodological quality of the studies the American
      Academy of Neurology classification of evidence for therapeutic intervention
      (Classes I-IV) was applied. CONCLUSION: Peripheral injury of the VIIth cranial
      nerve can have serious repercussions on the patient's functioning and quality of
      life. The recovery rate is related to the preservation of the nerve and to the
      cause of palsy. We obtained a third level of recommendation (level C); mime
      therapy could be effective to improve functional outcome in these patients.
      Evidence of specific treatment addressed to specific cause is lacking; likewise,
      no evidence is available on timing of intervention with respect to time of onset.
      Well-designed randomized controlled trials are required to evaluate the effect of
      rehabilitation in patients with facial palsy.

PMID- 22872181
TI  - Imaging case of the month: Bilateral internal auditory canal melanoma.

PMID- 22872182
TI  - Relationships among acculturative stress, sleep, and nondipping blood pressure in
      Korean American women.
AB  - Generally blood pressure (BP) should drop or dip by 10-20% during sleep. The
      phenomenon of nondipping BP during sleep has gained interest because of its
      association with various damaging effects to end-organs. This exploratory study
      examined nighttime nondipping BP, acculturative stress and quality of sleep in 30
      Korean American women. Acculturative stress and sleep quality were measured using
      the Revised Social, Attitudinal, Familial, and Environmental Acculturative Stress
      Scale (R-SAFE) and the Pittsburg Sleep Quality Index (PSQI), respectively.
      Participants' BP was monitored over a 24-hour period. Participants were
      categorized as dippers and nondippers based on the drop in nocturnal systolic BP.
      Of the 30 women, 8 (26.7%) were nondippers. A shorter sleep duration and more
      disturbed sleep were associated with nondipping and, interestingly, less
      acculturative stress was also associated with nondipping BP. Our finding supports
      that sleep evaluation is needed in caring for individuals with nondipping BP.

PMID- 22872183
TI  - Identification of the SGR6065 gene product as a sesquiterpene cyclase involved in
      (+)-epicubenol biosynthesis in Streptomyces griseus.
AB  - Recent bacterial genome sequencing projects have shown the presence of many
      putative sesquiterpene cyclase (SC) genes, especially in the Gram-positive,
      filamentous bacterial genus Streptomyces. We describe here the characterization
      of a SC gene (SGR6065, named gecA) from Streptomyces griseus. Overexpression of
      gecA in Streptomyces lividans produced a sesquiterpene, which was isolated and
      determined to be (+)-epicubenol using spectroscopic analyses. The N-terminal
      histidine-tagged GecA protein was produced in Escherichia coli. Incubation of the
      recombinant GecA protein with farnesyl diphosphate (FPP) yielded (+)-epicubenol
      as the major product. The K(m) value for FPP and the k(cat) value for (+)
      epicubenol formation were calculated to be 254 +/- 7.1 nM and 0.026 +/- 0.001 s(
      1), respectively. The k(cat)/K(m) value (0.10 s(-1) MUM(-1)) was broadly
      comparable to those reported for known bacterial SCs. (+)-Epicubenol was detected
      in the crude cell lysate of wild-type S. griseus, but not in a gecA-knockout
      mutant, indicating that GecA is a genuine (+)-epicubenol synthase. Although (+)
      epicubenol synthases have been previously purified and characterized from the
      liverwort Heteroscyphus planus and Streptomyces sp. LL-B7, no (+)-epicubenol
      synthase gene has been cloned to date. The gecA gene is thus the first example of
      an (+)-epicubenol synthase-encoding gene. (+)-Epicubenol production was not
      controlled by the microbial hormone A-factor that induces morphological
      differentiation and production of several secondary metabolites in S. griseus.

PMID- 22872184
TI  - Changes in the association between summer temperature and mortality in Seoul,
      South Korea.
AB  - The health impact of climate change depends on various conditions at any given
      time and place, as well as on the person. Temporal variations in the relationship
      between high temperature and mortality need to be explored in depth to explain
      how changes in the level of exposure and public health interventions modify the
      temperature-mortality relationship. We examined changes in the relationship
      between human mortality and temperature in Seoul, which has the highest
      population in South Korea, considering the change in population structure from
      1993-2009. Poisson regression models were used to estimate short-term temperature
      related mortality impacts. Temperature-related risks were divided into two "time
      periods" of approximately equal length (1993 and 1995-2000, and 2001-2009), and
      were also examined according to early summer and late summer. Temperature-related
      mortality in summer over the past 17 years has declined. These decreasing
      patterns were stronger for cardiovascular disease-related mortality than for all
      non-accidental deaths. The novel finding is that declines in temperature-related
      mortality were particularly noteworthy in late summer. Our results indicate that
      temperature-related mortality is decreasing in Seoul, particularly during late
      summer and, to a lesser extent, during early summer. This information would be
      useful for detailed public health preparedness for hot weather.

PMID- 22872185
TI  - Assessing the impact of thermal acclimation on physiological condition in the
      zebrafish model.
AB  - The zebrafish has become a valuable vertebrate model organism in a wide range of
      scientific disciplines, but current information concerning the physiological
      temperature response of adult zebrafish is rather scarce. In this study,
      zebrafish were experimentally acclimated for 28 days to 18, 26 or 34  degrees C
      and a suite of non-invasive and invasive methods was applied to determine the
      thermal dependence of zebrafish physiological condition. With decreasing
      temperature, the metabolic rate of zebrafish decreased, as shown by the
      decreasing oxygen uptake and ammonia excretion rates, limiting the critical
      swimming speed, probably due to a decreased muscle fibre power output. In
      response to exercise, fuel stores were mobilized to the liver as shown by the
      increased hepatosomatic index, liver total absolute energetic value and liver
      carbohydrate concentration but due to the low metabolic rate they could not be
      adequately addressed to power swimming activity at 18  degrees C. Conversely, the
      increased metabolic performance at high temperature came with an increased
      metabolic cost resulting in decreased energy status reflected particularly well
      by the non-invasive condition factor and invasive measures of carcass protein
      concentration, carcass total absolute energetic value and liver carbohydrate
      concentration. We showed that the combined measurement of the relative condition
      factor and critical swimming speed is a powerful non-invasive tool for long-term
      follow-up studies. Invasive methods were redundant for measuring general energy
      status but they provided detailed information concerning metabolic
      reorganization. With this study we proved that the usefulness of the zebrafish as
      a model organism can easily be expanded to include physiological studies and we
      provided a reference dataset for the selection of measures of physiological
      responses for future studies using the zebrafish.

PMID- 22872186
TI  - The capacity for paracellular absorption in the insectivorous bat Tadarida
      brasiliensis.
AB  - Water-soluble nutrients are absorbed by the small intestine via transcellular and
      paracellular processes. The capacity for paracellular absorption seems greater in
      fliers than in nonfliers, although that conclusion rests mainly on a comparison
      of flying birds and nonflying mammals because only two frugivorous bat species
      have been studied. Furthermore, the bats studied so far were relatively large
      (>85 g, compared with most bat species which are <20 g) and were not insectivores
      (like about 70 % of bat species). We studied the small (11 g) insectivorous bat
      Tadarida brasiliensis and tested the prediction that the capacity for
      paracellular absorption would be as high as in the other bat and avian species
      studied so far, well above that in terrestrial, nonflying mammals. Using standard
      pharmacokinetic technique, we measured the extent of absorption (fractional
      absorption = f) of inert carbohydrate probes: L-arabinose (MM = 150.13) absorbed
      exclusively by paracellular route and 3OMD-glucose (MM = 194) absorbed both
      paracellularly and transcellularly. As predicted, the capacity of paracellular
      absorption in this insectivorous bat was high (L-arabinose f = 1.03 +/- 0.14) as
      in other frugivorous bats and small birds. Absorption of 3OMD-glucose was also
      complete (f = 1.09 +/- 0.17), but >80 % was accounted for by paracellular
      absorption. We conclude that passive paracellular absorption of molecules of the
      size of amino acids and glucose is extensive in this bat and, generally in bats,
      significantly higher than that in nonflying mammals, although the exact extent
      can be somewhat lower or higher depending on molecule size, polarity and charge.

PMID- 22872187
TI  - Evaluation in vitro of the efficacy of colistin methanesulfonate against biofilm
      forming multidrug-resistant Pseudomonas aeruginosa (MDRP).
AB  - The aim of this study was to evaluate in vitro the efficacy of clinically using
      colistin methanesulfonate against biofilm-forming multidrug-resistant Pseudomonas
      aeruginosa (MDRP), with minimum inhibitory concentrations (MICs) of
      ciprofloxacin, imipenem, and amikacin showing >=4, 16, and 32 MUg/ml,
      respectively, by disk diffusion susceptibility testing (CLSI document M100-S21).
      The minimum eradication biofilm concentration (MBEC) of colistin methanesulfonate
      for strain MDRP-YMD isolated from a patient's urine, which formed a biofilm on
      plastic pegs attached to a microplate lid, was compared with that of P.
      aeruginosa ATCC27853 for quality control testing with MICs of ciprofloxacin,
      imipenem, and amikacin showing <=1, 4, and 16 MUg/ml, respectively. In an uneven
      biofilm approximately 10 MUm thick, as determined with confocal laser scanning
      microscopy (CLSM), ratios of MBEC to MIC of colistin methanesulfonate against
      strains MDRP-YMD and ATCC27853 were 10.5 and 8.0, whereas those of minimum
      bactericidal concentration (MBC) to MIC in planktonic cells were 1.0 and 2.0
      MUg/ml, respectively. Morphological examination using scanning electron
      microscopy and CLSM verified that embedded cells in biofilm matrices of the two
      strains were disrupted and died under the MBEC. Therefore, bactericidal effects
      of colistin methanesulfonate on biofilm-forming cells of strain MDRP-YMD as well
      as strain ATCC27853 were significantly decreased compared with those on the
      planktonic cells.

PMID- 22872188
TI  - Pharmacokinetics of glycopeptide antibiotics in children.
AB  - Vancomycin (VAN) and teicoplanin (TEIC) are the glycopeptide antimicrobials
      commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA)
      infection in pediatric patients. This study examined the relationship between the
      initial doses of glycopeptides and the trough serum concentrations of drugs in
      children, with the intent to determine their optimal dosing. Consecutive patients
      between 0 and 18 years of age, who between June 2003 and December 2010 were
      treated with VAN (n = 50) or TEIC (n = 187) for >48 h, were enrolled in this
      study. Patients were classified into three groups depending on the dose
      administered: lower than, equal to, or higher than the recommended dosage by each
      package insert. The patient's age, body weight, dose of antimicrobial
      administered during the first 24 h, median trough serum concentrations between 48
      and 72 h after the onset of treatment, and serum creatinine concentrations before
      and 3 and 7 days after its administration were recorded. Median trough
      concentrations for VAN and TEIC in the three dosage groups were 8.0, 8.5, and
      13.0 MUg/ml, and 11.8, 13.0, and 17.7 MUg/ml, respectively. The median serum
      creatinine concentrations did not rise significantly between baseline and 3 and 7
      days after the onset of treatment in any treatment group. Therapeutic serum
      concentrations of VAN and TEIC to treat MRSA infections, 15-20 and >=20 MUg/ml,
      respectively, were rarely reached by the administration of standard doses of
      drugs for children.

PMID- 22872189
TI  - Enhancing Supportive-Educative Nursing Systems to Reduce Risk of Post-Breast
      Cancer Lymphedema.
AB  - This study describes the use of data regarding self-care agency to enhance a
      supportive-educative nursing system for breast cancer survivors to reduce the
      risk of developing lymphedema post surgery. Impetus for this study came from the
      analysis of participant feedback from a parent study (Lance Armstrong Foundation
      pilot study) that sought to plan an educational program for nurses that will
      improve their supportive-educative nursing system when working with breast cancer
      survivors. The goal is to enable these women to reduce the risk of lymphedema
      post surgery. The parent study examined a bundled behavioral-educative
      intervention, which included standard lymphedema education coupled with Modified
      Manual Lymph Drainage (MMLD) to reduce the risk of developing lymphedema in newly
      diagnosed breast cancer survivors. Based upon the feedback received from the
      parent study, the research team recognized that many of the participants were not
      fully following the recommendations of the intervention protocol. In order for
      nurses to help patients develop self-care agency (SCA) (Orem, 2001) to engage in
      actions that addressed the self-care requisites associated with post-breast
      cancer surgery, these nurses needed to refine their intervention skills. Prior to
      the development of a program for the nurses, the research team conducted a study
      to explore the state of power related to SCA of the study participants. The
      information obtained from this was then used in the development of an educational
      program for bundled intervention. Both motivational interviewing (Miller &
      Rollnick, 2002) and solution-focused therapy (Berg & DeJong, 1996) were
      incorporated into the educational program for the research nurse team to
      strengthen and improve supportive-educative nursing systems. Supportive-educative
      systems of care that integrate self-care deficit nursing theory, motivational
      interviewing, and solution-focused therapy can assist patients to develop and
      sustain self-care agency.

PMID- 22872192
TI  - Reliability of cancer family history reported by parents in a case-control study
      of childhood leukemia.
AB  - PURPOSE: To investigate the reliability of family history of cancer reported by
      parents of children with acute lymphoblastic leukemia (ALL) and parents of
      healthy control children. METHODS: A total of 301 parents were selected based on
      positive or negative family history of cancer at baseline, case-control status,
      and gender of the respondent (mother or father). Baseline responses were compared
      with responses at the second interview using the same questionnaire. Reliability
      was measured using proportion of overall agreement, Cohen's kappa, and Cronbach's
      alpha; a logistic regression model was also used to assess the role of the case
      control status on overall agreement as the dependent variable. RESULTS: The
      overall agreement between interviews was high and similar for cases (85 %) and
      controls (86 %); there were no consistent effects of respondent gender, age at
      first interview, or time elapsed between interviews on agreement measures.
      Agreement measures did not materially vary according to whether respondents were
      reporting about their mothers, fathers, or siblings. CONCLUSIONS: The study
      showed very good reliability of reporting family history among young parents of
      children affected with leukemia and parents of healthy control children.

PMID- 22872193
TI  - Effects of the toric intraocular lens on correction of preexisting corneal
      astigmatism.
AB  - PURPOSE: To examine the effects of a toric intraocular lens (IOL) on the
      correction of preexisting corneal astigmatism after cataract surgery. METHODS:
      Fifty eyes that underwent phacoemulsification were enrolled in three group: (1)
      eyes with corneal astigmatism >=1.0 diopter (D) that received a toric IOL (Alcon
      SN6AT) (toric), (2) eyes with astigmatism >=1.0 D that received a nontoric IOL
      (high-astigmatism group), and (3) eyes with astigmatism <1.0 D that received the
      nontoric IOL (low-astigmatism group). Refractive and corneal astigmatism,
      astigmatic change, and uncorrected visual acuity (UCVA) were examined. RESULTS:
      The postoperative refractive astigmatism in the toric and low-astigmatism groups
      was significantly lower than that of the high-astigmatism group (P <= 0.0040),
      and the reduction in the refractive astigmatism was greater in the toric than in
      the high- and low-astigmatism groups (P < 0.0001), although the corneal
      astigmatism was greatest in the toric group, followed by the high- and low
      astigmatism groups (P < 0.0001). The mean UCVA in the toric and low-astigmatism
      groups was better than that in the high-astigmatism group (P < 0.0001).
      CONCLUSIONS: The toric IOL proved effective in astigmatism correction, and both
      the residual astigmatism and UCVA in the eyes with the the toric IOL were better
      than those in the eyes with high astigmatism and were comparable to those in the
      eyes with low astigmatism.

PMID- 22872194
TI  - Selective CO2 adsorption in a metal-organic framework constructed from an organic
      ligand with flexible joints.
AB  - A metal-organic framework (SNU-110) constructed from an organic ligand with
      flexible joints exhibits selective CO(2) adsorption over N(2), O(2), H(2) and
      CH(4) gases.

PMID- 22872195
TI  - About price and value of scientific publications: criticism or indignation?

PMID- 22872196
TI  - [Visual impairment impact on the quality of life of the elderly population that
      uses the public health care system from the western countryside of Pernambuco
      State, Brazil].
AB  - PURPOSE: To evaluate the impact of visual impairment on the quality of life of
      the elderly population living in the western countryside of Pernambuco State,
      located in northeast of Brazil. METHODS: Five hundred and eighty subjects over 59
      years of age were interviewed using the Visual Functioning Questionnaire (VFQ).
      All subjects underwent complete eye examination. The results of the quantitative
      parameters were expressed by mean +/- SD. The results of categorical parameters
      were expressed by their frequencies. RESULTS: Mean age was of 70 +/- 8.1 years.
      About 86% of the interviewed elderly were illiterate or had incomplete education.
      The mean complaints were low visual acuity (71.1%) and itching/burning (69.0%).
      The visual acuity was not normal in 37.4% of the elderly. About 75.0% of the
      subjects reported to have regular or bad health, and 77.0% reported to have
      regular or bad vision. The reported quality of life decreased according to the
      worsening of the visual acuity. CONCLUSION: Visual impairment had a negative
      impact on the quality of life of the elderly population from the western
      countryside of Pernambuco State.

PMID- 22872197
TI  - Optical aids for low vision: use of the Internet to guide teachers of the
      visually impaired.
AB  - PURPOSES: To describe and interpret teachers' opinions about and responsiveness
      to guidance on optical aids for low vision. METHODS: It was conducted a cross
      sectional analytical study. The convenience, non-random sample consisted of 58
      teachers from the public school network of the city of Campinas. It was
      constructed and applied a structured questionnaire, available online at the
      assessed website. For qualitative data collection it was conducted an exploratory
      study using the focus group technique. RESULTS: Responses expressed, for the most
      part, a marked interest in the website, its easiness of access, and the
      comprehensive nature of the information provided. Most people reported frequent
      use of the Internet to seek information, and found it easier to access the
      Internet at home. Among the qualitative aspects of the evaluation, we should
      mention the perceived importance of the website as a source of information,
      despite some criticism about the accessibility and reliability of the information
      found on the Internet. CONCLUSION: Teachers' need for training to deal with
      visually impaired students and their positive response to advice and information
      lead to the conclusion that web-based guidelines on the use of optical aids were
      considered beneficial to ease the understanding of visual impairment and the
      rehabilitation of the affected subjects.

PMID- 22872198
TI  - [Amsler grid and visual field on screening for chloroquine retinopathy].
AB  - PURPOSE: To compare the modified Amsler grid to the Humphrey((r)) 10-2 red visual
      field in chloroquine users for the detection of early maculopathy, and to
      correlate with the risk variables. METHODS: The study included 116 eyes of 58
      patients followed at the Department of Ophthalmology of Hospital do Servidor
      Publico Estadual de Sao Paulo, from April, 2006 to April, 2008. All users had
      normal fundus and more than 2 years of chloroquine therapy. Their clinical data
      were evaluated and they underwent visual acuity examination, fundus
      biomicroscopy, visual field and Amsler grid. RESULTS: The incidence of early
      maculopathy was 7 to 10%, depending on the examination considered. The agreement
      between the Amsler grid and visual field was low. There was statistical
      significance with the use of high daily dose, elevated cumulative dose and low
      visual acuity in patients whose eyes had both abnormal tests; patient age and
      duration of treatment did not show good correlation in these cases, but their
      averages (67.4 years and 8.4 years, respectively) were within the range of high
      risk factors. CONCLUSIONS: The study suggests that Amsler can be useful in
      complementing the information on the visual field for chloroquine retinopathy
      periodic screening, especially for those patients who present high risk factors
      well established, selecting better candidates for objective tests, such as HD OCT
      and mfERG.

PMID- 22872199
TI  - Viral contamination during sequential phacoemulsification surgeries in an
      experimental model.
AB  - PURPOSE: To determine the incidence of Piry virus contamination among surgical
      instruments used with disposable accessories for phacoemulsification during
      sequential surgeries. METHODS: An experimental model was created with 4 pigs'
      eyes that were contaminated with Piry virus and 4 pigs' eyes that were not
      contaminated. Phacoemulsification was performed on the eyes, alternating between
      the contaminated and non-contaminated eyes. From one surgery to another, the
      operating fields, gloves, scalpel, tweezers, needles, syringes, tips and bag
      collector from the phacoemulsification machine were exchanged; only the hand
      piece and the irrigation and aspiration systems were maintained. RESULTS: In the
      collector bag, three samples from the contaminated eyes (3/4) were positive, and
      two samples from the non-contaminated (2/4) eyes were also positive; at the tip,
      one sample from the contaminated eyes (1/4) and two samples of the non
      contaminated eyes (2/4) yielded positive results. In the irrigation system, one
      sample from a non-contaminated eye (1/4) was positive, and in the aspiration
      system, two samples from contaminated eyes (2/4) and two samples from non
      contaminated eyes (2/4) were positive. In the gloves, the samples were positive
      in two samples from the non-contaminated eyes (2/4) and in two samples from the
      contaminated eyes (2/4). In the scalpel samples, three contaminated eyes (3/4)
      and none of the non-contaminated eyes (0/4) were positive; finally, two samples
      from the anterior chambers of the non-contaminated eyes gathered after surgery
      were positive. CONCLUSIONS: In two non-contaminated eyes, the presence of genetic
      material was detected after phacoemulsification surgery, demonstrating that the
      transmission of the genetic material of the Piry virus occurred at some point
      during the surgery on these non-contaminated eyes when the hand piece and
      irrigation and aspiration systems were reused between surgeries.

PMID- 22872200
TI  - Azithromycin 1.5% ophthalmic solution: efficacy and treatment modalities in
      chronic blepharitis.
AB  - PURPOSE: To assess the efficacy of topical 1.5% azithromycin in the treatment of
      moderate to severe chronic blepharitis and to compare the efficacy of two
      different treatment modalities. METHODS: A randomized clinical trial included 67
      patients with chronic anterior and/or posterior blepharitis, followed-up for 3
      months. Signs and symptoms were graded according to severity. Patients were
      randomized into two groups: 33 patients in group I and 34 patients in group II.
      Group I patients were treated with topical 1.5% azithromycin twice a day for
      three days, and Group II patients were treated with topical 1.5% azithromycin
      twice a day for three days then at bedtime for the rest of the month. All
      patients were instructed to apply warm compresses and an eye-friendly soap twice
      daily. RESULTS: Patients in both groups tolerated the treatment with minimal
      irritation. A significant improvement in signs and symptoms was noted at the one
      week follow-up visit. Group II showed a more pronounced and longer-lasting
      improvement that persisted after three months of follow-up. CONCLUSION: Topical
      1.5% azithromycin ophthalmic solution is an effective treatment option for
      chronic blepharitis. In moderate to severe blepharitis, a one month treatment is
      safe and shows better improvement than the three-day protocol with no significant
      relapse until three months of follow-up.

PMID- 22872201
TI  - Correlation between central subfield thickness, visual acuity and structural
      changes in diabetic macular edema.
AB  - PURPOSE: To correlate the central subfield thickness (CST) measured by CirrusTM
      SD-OCT with best-corrected visual acuity (BCVA) and structural changes in
      diabetic macular edema (DME). METHODS: The transversal study evaluated 200
      patients with non-proliferative diabetic retinopathy (NPDR) and selected 55 eyes
      with DME between January, 2010 and April, 2011. Spectral domain OCT was performed
      in patients with type 2 diabetes and DME. CST and BCVA were correlated with the
      edema morphology and the ELM (external limiting membrane) integrity. Statistical
      tests were applied to validate the results. RESULTS: There was no difference
      between genders in the NPDR classification. 47.3% of the patients showed moderate
      NPDR. The CST average for male was of 393.58 um and 434.16 um for female, with no
      statistically significant difference. The patients with continuous ELM showed
      lower CST average (368.73 um) than those with disrupted ELM (521.43 um). There
      was a strong correlation between the macular volume and CST (59.63%), but poor
      correlation between age and CST (2.9%). Also, there was a significant difference
      between the average CST and the type of macular edema. Patients with serous
      detachment showed higher CST average (488.71 um) than those with cystoid macular
      edema (CME) and diffuse edema. Patients with severe NPDR showed higher CST
      average (491.45 um), if compared to mild and moderate NPDR. Cystoid macular edema
      was the most common type of edema (49.1%) and showed the worse VA. Patients with
      disrupted ELM showed worse BCVA. Patients with higher CST showed worse BCVA.
      There was a significant difference between the CST average of the case group
      (407.6 +/- 113,1 um) and the control group (diabetic patients without DME: 252 +/
      12.5 um). There was also a significant difference in the BCVA variables and
      macular volume between case and control groups. CONCLUSION: The study suggests
      that the CST of diabetic patients with edema is higher than the control group,
      the increase in CST of diabetic patients with edema leads to worsening of BCVA
      and macular volume. Continuous ELM showed lower CST average, and the serous
      detachment showed higher CST average. CirrusTM proved to be an important tool in
      the DME evaluation.

PMID- 22872202
TI  - Strabismus surgery learning for Ophthalmology residents of university service.
AB  - PURPOSE: To verify Ophthalmology resident's and supervisor's perceptions
      regarding learning and teaching strabismus surgery. DESIGN: Descriptive Study.
      METHODS:  SUBJECTS: 1(st) and 2(nd) year residents. Each resident studied the
      standard strabismus surgery technique on a CD-ROM, then performed a rabbit rectus
      muscle recession and a strabismus surgery on a patient. A structured
      questionnaire was handed to the residents, and the authors made observations
      including variables referring to the surgical technique applied, self-evaluation
      of this technique and if appropriate training was given. RESULTS: Thirty-eight
      questionnaires were analysed. All 1(st) year residents (R1) had had some
      difficulty remembering the surgery sequence and 69.6% of 2(nd) year residents
      (R2). Concerning the surgical material handling, 93.3% of R1 and 52.2% of R2 had
      had any difficulty. The residents reported that during the surgery in humans, 50%
      remembered the experimental stage and that this training completely fulfilled
      their needs for 47% and partially for other 47%. CONCLUSION: Experimental
      surgery, more practice opportunities and resident's supervision may improve the
      teaching of strabismus surgery.

PMID- 22872203
TI  - Refractive lens exchange with a multifocal diffractive aspheric intraocular lens.
AB  - PURPOSE: To evaluate the safety, efficacy and predictability after refractive
      lens exchange with multifocal diffractive aspheric intraocular lens implantation.
      METHODS: Sixty eyes of 30 patients underwent bilateral implantation with
      AcrySof((r)) ReSTOR((r)) SN6AD3 intraocular lens with +4.00 D near addition.
      Patients were divided into myopic and hyperopic groups. Monocular best corrected
      visual acuity at distance and near and monocular uncorrected visual acuity at
      distance and near were measured before and 6 months postoperatively. RESULTS:
      After surgery, uncorrected visual acuity was 0.08 +/- 0.15 and 0.11 +/- 0.14
      logMAR for the myopic and hyperopic groups, respectively (50% and 46.67% of
      patients had an uncorrected visual acuity of 20/20 or better in the myopic and
      hyperopic groups, respectively). The safety and efficacy indexes were 1.05 and
      0.88 for the myopic and 1.01 and 0.86 for the hyperopic groups at distance
      vision. Within the myopic group, 20 eyes remained unchanged after the surgery,
      and 3 gained >2 lines of best corrected visual acuity. For the hyperopic group, 2
      eyes lost 2 lines of best corrected visual acuity, 21 did not change, and 3 eyes
      gained 2 lines. At near vision, the safety and efficacy indexes were 1.23 and
      1.17 for the myopic and 1.16 and 1.13 for the hyperopic groups. Best corrected
      near visual acuity improved after surgery in both groups (from 0.10 logMAR to
      0.01 logMAR in the myopic group, and from 0.10 logMAR to 0.04 logMAR in the
      hyperopic group). CONCLUSIONS: The ReSTOR((r)) SN6AD3 intraocular lens in
      refractive lens exchange demonstrated good safety, efficacy, and predictability
      in correcting high ametropia and presbyopia.

PMID- 22872204
TI  - [Comparative study between gelatinous and hard spheres of silicone in rabbit
      eviscerated scleral cavity].
AB  - PURPOSE: To evaluate and to compare the biocompatibility of gelatinous and hard
      silicone spheres placed into eviscerated scleral cavities of rabbits. METHOD:
      Thirty rabbits underwent right eye evisceration surgery and replacement of
      orbital volume using gelatinous (Group I) or hard silicone (Group II) spheres.
      Seven, 30 and 90 days after the surgical procedure, clinical assessment,
      ultrasound of the orbit, histological and morphometric evaluation of the
      pseudocapsule were performed. Data was submitted to statistical analysis.
      RESULTS: Similarity of tissue response was observed with both materials. Two
      gelatinous and one hard silicone spheres had extrusion. The pseudocapsule around
      the gelatinous spheres was better organized, thinner and with less inflammatory
      reaction. CONCLUSIONS: Both spheres had good integration to the orbital tissue in
      rabbit eviscerated cavities.

PMID- 22872205
TI  - Profile of ocular and systemic characteristics in Mobius sequence patients from
      Brazil and Italy.
AB  - PURPOSE: To compare the profiles and clinical findings of a series of patients
      with Mobius sequence from Brazil with a series from Italy. METHODS: This is a
      multicenter study, which includes 46 Mobius sequence patients from Brazil and 20
      from Italy. Socio-demographic, gestational, and neonatal profile characteristics
      were collected from interviews with the guardians of the Mobius sequence patients
      and compared. The Mobius sequence patients were submitted to an ophthalmologic
      examination and systemic malformations were also evaluated. RESULTS: Misoprostol
      was used in the first trimester of pregnancy by 26 (56.5%) of the mothers of the
      Mobius sequence patients in the Brazilian series and was not used by any of the
      Italian mothers. The mean age of the Brazilian Mobius sequence patients was 89.95
      +/- 7.79 months and the mean age of the Italian patients was 102.6 +/- 22.94
      months (P=0.6105; Mann-Whitney test). Brazilian mothers had a significantly lower
      education level (P=0.0002; Fisher's exact test) and Italian mothers had
      significantly more stable relationships (p=0.0002; Fisher's exact test). The
      frequency of ocular and systemic abnormalities was similar in both series.
      CONCLUSION: Adverse events during pregnancy varied between both groups. A history
      of misoprostol use during early pregnancy was present only in Brazilian mothers,
      who had lower levels of education and less frequent stable marital statuses.
      Clinical findings were similar between both groups of patients.

PMID- 22872206
TI  - Embryonal rhabdomyosarcoma of the caruncle in a 4 year-old boy: case report.
AB  - Rhabdomyosarcoma is a rare tumor, with an annual incidence of 4.3 cases per
      million children. Even thought, it is the most common soft tissue sarcoma in
      childhood, with a mean age of 6 to 8 years at diagnosis. A 4 year-old boy
      presented with a history of a fast growing (1-month) nodular lesion in the
      caruncle of his left eye. Slit lamp examination showed a vascularized solid
      nodular lesion in the semilunar fold. The lesion was surgically removed obtaining
      infiltrated edges with tumoral cells. A second surgery was performed with free
      tumour edges. The diagnosis of embryonal rhabdomyosarcoma, botryoid type, of
      intermediate differentiation was made. The treatment for botryoid
      rhabdomyosarcoma is basically surgical with the combined use of adjuvant
      polychemotherapy. In adolescent or adult patients (not in infants where growth
      bone disturbances can occur) external beam radiotherapy can be combined with
      chemotherapy. Rhabdomyosarcomas of the conjunctiva without orbital extension are
      rarely reported. We presented a case of a child with a rare tumor which we had a
      high suspicion of malignancy and early diagnosis and treatment and child is free
      of systemic disease 6 and half years later. Our research group believes that the
      key in these tumors is the high index of suspicion and early treatment.

PMID- 22872207
TI  - [Unilateral retinitis pigmentosa secondary to eye injury: case report].
AB  - Retinitis pigmentosa is a group of diseases caused by genetic changes that lead
      to progressive degeneration of photoreceptors, rods mainly. In general, it has
      bilateral presentation. This study is a case report of a patient with unilateral
      involvement of the retina, similar to the characteristics of retinitis
      pigmentosa, and an old ocular trauma history. It describes her history and
      ophthalmologic findings.

PMID- 22872208
TI  - Botox(r) after Botox(r) - a new approach to treat diplopia secondary to cosmetic
      botulinic toxin use: case reports.
AB  - A new technique for the treatment of diplopia secondary to cosmetic botulinum
      toxin A use is described. In this interventional case reports, two consecutive
      patients who developed diplopia after periocular cosmetic use of botulinum toxin
      A were treated with intramuscular botulinum toxin A injection into the antagonist
      extraocular muscle. Diplopia resolved in both patients in less than 1 week with
      no side effects or complications. In conclusion, the injection of intramuscular
      botulinum toxin A is an encouraging option for treatment of diplopia secondary to
      botulinum toxin A use for facial lifting.

PMID- 22872209
TI  - [Congenital corneal anesthesia: case reports].
AB  - Case series of nine patients with congenital corneal anesthesia, six of them
      showed systemic changes in association with the ocular status. Three patients
      were submitted to electromyography, two showed isolated bilateral ophthalmic
      ramus alteration. Two patients had initial visual acuity better than 20/60 and
      six had final best corrected visual acuity better than 20/60 at the last visit.
      All of them were treated surgically and developed cornea opacities of variable
      sizes. Treatment of corneal congenital anesthesia must be performed as soon as
      possible to avoid corneal opacification. Systemic investigation, close follow-up
      and preparing the family for longterm and multidisciplinary approach are crucial
      to maintain the ocular health.

PMID- 22872210
TI  - Boston type I keratoprosthesis: Review.
AB  - Regardless of significant progress in the field of corneal transplantation to
      treat corneal opacification, some cases of corneal blindness still present a poor
      prognosis for conventional penetrating keratoplasty. In patients with repeated
      graft failure and/or with severe ocular surface disease, the Boston type I
      keratoprosthesis (type I BKPro) has become a viable option. Modifications in its
      design and postoperative management have improved the long-term outcomes of
      visual acuity, retention, and postoperative infection rates. These advances made
      the type I BKPro be considered a safe alternative for visual rehabilitation in
      many patients with corneal pathologies. However, postoperative handle of chronic
      comorbidities, such as glaucoma, is still critical for preserving the visual
      gains achieved with BKPro.

PMID- 22872211
TI  - Nonadiabatic dynamics of a truncated indigo model.
AB  - Indigo (1) is stable when exposed to ultraviolet light. We employ electronic
      structure calculations and nonadiabatic trajectory surface-hopping dynamics
      simulations to study the photoinduced processes and the photoprotection mechanism
      of an indigo model, bispyrroleindigo (2). Consistent with recent static ab initio
      calculations on 1 and 2 (Phys. Chem. Chem. Phys., 2011, 13, 1618), we find an
      efficient deactivation process that proceeds as follows. After vertical
      photoexcitation, the S(1)(pipi*) state undergoes an essentially barrierless
      intramolecular single proton transfer and relaxes to the minimum of an S(1)
      tautomer, which is structurally and energetically close to a nearby conical
      intersection that acts as a funnel to the S(0) state; after this internal
      conversion, a reverse single hydrogen transfer leads back to the equilibrium
      structure of the most stable S(0) tautomer. This deactivation process is
      completely dominant in our semiempirical OM2/MRCI nonadiabatic dynamics
      simulations. The other two mechanisms considered previously, namely excited-state
      intramolecular double proton transfer and trans-cis double bond isomerization,
      are not seen in any of the 325 trajectories of the present surface-hopping
      simulations. On the basis of the computed time-dependent populations of the S(1)
      state, we estimate an S(1) lifetime of about 700 fs for 2 in the gas phase.

PMID- 22872212
TI  - Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion
      of glucose-dependent insulinotropic polypeptide from intestinal K cells in
      rodents.
AB  - AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an
      enteroendocrine hormone that promotes storage of glucose and fat. Its secretion
      from intestinal K cells is triggered by nutrient ingestion and is modulated by
      intracellular cAMP. In view of the proadipogenic actions of GIP, this study aimed
      to identify pathways in K cells that lower cAMP levels and GIP secretion.
      METHODS: Murine K cells purified by flow cytometry were analysed for expression
      of G(alphai)-coupled receptors by transcriptomic microarrays. Somatostatin and
      cannabinoid receptor expression was confirmed by quantitative RT-PCR. Hormone
      secretion in vitro was measured in GLUTag and primary murine intestinal cultures.
      cAMP was monitored in GLUTag cells using the genetically encoded sensor Epac2
      camps. In vivo tolerance tests were performed in cannulated rats. RESULTS:
      Purified murine K cells expressed high mRNA levels for somatostatin receptors
      (Sstrs) Sstr2, Sstr3 and Sstr5, and cannabinoid receptor type 1 (Cnr1, CB1).
      Somatostatin inhibited GIP and glucagon-like peptide-1 (GLP-1) secretion from
      primary small intestinal cultures, in part through SSTR5, and reduced cAMP
      generation in GLUTag cells. Although the CB1 agonist methanandamide (mAEA)
      inhibited GIP secretion, no significant effect was observed on GLP-1 secretion
      from primary cultures. In cannulated rats, treatment with mAEA prior to an oral
      glucose tolerance test suppressed plasma GIP but not GLP-1 levels, whereas the
      CB1 antagonist AM251 elevated basal GIP concentrations.
      CONCLUSIONS/INTERPRETATION: GIP release is inhibited by somatostatin and CB1
      agonists. The differential effects of CB1 ligands on GIP and GLP-1 release may
      provide a new tool to dissociate secretion of these incretin hormones and lower
      GIP but not GLP-1 levels in vivo.

PMID- 22872213
TI  - Reduced Socs3 expression in adipose tissue protects female mice against obesity
      induced insulin resistance.
AB  - AIMS/HYPOTHESIS: Inflammation in obesity increases the levels of the suppressor
      of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological
      importance of this protein in regulating whole-body insulin sensitivity in
      obesity is not known. METHODS: We generated Socs3 floxed (wild-type, WT) and
      Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained
      on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time
      body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed.
      RESULTS: The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO
      mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using
      computed tomography (CT) imaging, irrespective of diet or sex. On a control chow
      diet there were no differences in insulin sensitivity or glucose tolerance. When
      fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as
      well as lower fasting glucose and insulin levels compared with WT littermates.
      Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET)
      imaging demonstrated that improved insulin sensitivity was due to elevated
      adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in
      adipose tissue was associated with enhanced levels and activating phosphorylation
      of insulin receptor substrate-1 (IRS1). CONCLUSIONS/INTERPRETATION: These data
      demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is
      effective for improving whole-body insulin sensitivity in obesity.

PMID- 22872214
TI  - Brief report: Asperger's syndrome and sibling birth order.
AB  - Prior investigations suggest that birth order position may be associated with the
      risk for developing a pervasive developmental disorder. This retrospective chart
      review examined the birth order status of 29 psychiatrically-referred patients
      with Asperger's Syndrome (AS). Eighty-six percent of the subjects were first
      born. The finding was statistically significant when compared to an expected
      random distribution of AS subjects chi(2) (1, N = 29) = 9.18, p < 0.01. The
      reasons for such an association are unclear though birth stoppage, obstetric
      complications, and immunological mechanisms may play a role.

PMID- 22872215
TI  - Prediction of massive blood loss in scoliosis surgery from preoperative
      variables.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To identify predictors of
      massive blood loss after scoliosis surgery. SUMMARY OF BACKGROUND DATA: Scoliosis
      surgery may be associated with considerable blood loss. Many blood conservation
      techniques have been used to reduce the allogeneic transfusion. An ability to
      identify patients with high risk of massive blood loss preoperatively may be
      helpful for appropriate use of these techniques. METHODS: Data of patients
      undergoing scoliosis surgery between June 1, 2011, and October 31, 2011, were
      collected. Preoperative information and total blood loss, which was calculated as
      the sum of intraoperative and postoperative estimated blood loss, were recorded.
      Patients were divided into 2 groups, retrospectively: group A (n = 95) with the
      total blood loss more than 30% of estimated blood volume and group B (n = 64)
      with the total blood loss of 30% of estimated blood volume or less. Preoperative
      data were compared between the groups. Significant variables were selected for a
      forward stepwise binary logistic regression analysis to determine the independent
      risk factors of massive blood loss. RESULTS: More than half of the patients
      (59.7%) undergoing scoliosis surgery had massive blood loss. Patients in group A
      were shorter (P = 0.01) and had larger preoperative Cobb angle (P < 0.01), more
      levels fused (P < 0.01), and more osteotomies (P < 0.01) than those in group B.
      Preoperative Cobb angle more than 50o (P = 0.017, odds ratio = 2.47, 95%
      confidence interval: 1.17-5.20), the number of fused levels more than 6 (P =
      0.014, odds ratio = 3.70, 95% confidence interval: 1.31-10.49), and osteotomy (P
      = 0.000, odds ratio = 4.64, 95% confidence interval: 1.97-10.94) were determined
      to be the independent risk factors of massive blood loss in scoliosis surgery.
      CONCLUSION: Risk of massive blood loss (total blood loss > 30% of estimated blood
      volume) in patients with scoliosis could increase, if they (1) had preoperative
      Cobb angle larger than 50o or (2) planned to undergo osteotomy or fusion of more
      than 6 levels.

PMID- 22872216
TI  - Can altering motions, postures, and loads provide immediate low back pain relief:
      a study of 4 cases investigating spine load, posture, and stability.
AB  - STUDY DESIGN: A quantitative biomechanical analysis of mechanism of pain
      alteration in 4 cases of low back pain. OBJECTIVE: To investigate the
      contributions of a number of biomechanical factors associated with pain
      alteration. SUMMARY OF BACKGROUND DATA: Some clinicians use mechanically based
      manual interventions in attempt to reduce low back pain. However, the mechanism
      of pain alteration remains unknown. METHODS: A sample was formed with 4 patients
      with low back pain seeking consults for pain relief. All could produce "catches"
      of pain with movement. Manual interventions involving coached changes in motion
      and muscle activation attempted to reduce pain. Electromyographic and kinematic
      data were collected before and after intervention. These data were input to an
      anatomically detailed spine model that calculated muscle force, joint compression
      and shear, and spine stability. RESULTS: Using a clinically significant criterion
      of pain reduction of 2 or more, 3 of 4 subjects reduced pain immediately upon the
      intervention. Using a change of 10% as a criterion for biological significance
      for kinematic and kinetic variables, each subject demonstrated a different
      reaction. For example, subject 1 demonstrated increased stability, subject 2
      increased mediolateral shear, subject 3 increased mediolateral shear and
      decreased spine flexion, and subject 4 increased stability. The pain-reducing
      interventions required to obtain these results were also different for each
      individual. CONCLUSION: Immediate pain reduction can be achieved by altering
      muscle-activation and movement patterns. However, the combination for optimal
      success seems to be different for every individual. Pain provocation tests help
      to "tune" the intervention. This also suggests that patient-classification
      schemes may need more refinement to address this heterogeneity.

PMID- 22872217
TI  - Antifibrinolytic agents reduce blood loss during pediatric vertebral column
      resection procedures.
AB  - STUDY DESIGN: Retrospective multicenter review. OBJECTIVE: To evaluate the effect
      of intraoperative antifibrinolytic (AF) agents on blood loss associated with
      vertebral column resection (VCR) procedures for pediatric patients. SUMMARY OF
      BACKGROUND DATA: VCR procedures may be associated with substantial blood loss.
      METHODS: A multicenter review of 147 patients (aged <21 yr) who underwent VCR as
      part of their spinal deformity correction was conducted. Estimated blood loss
      (EBL) was calculated as percentage of blood volume (BV) (EBL/BV * 100), which was
      normalized on the basis of the number of vertebral levels removed (%BV/level).
      The use of AF agents was noted (tranexamic acid [TXA], aminocaproic acid,
      aprotinin, none) and based on surgeons' choice. EBL was compared using analysis
      of covariance (controlling for deformity magnitude) (P < 0.05). RESULTS: Average
      preoperative major deformity (kyphosis or scoliosis) was 97 degrees  +/- 31
      degrees . The average number of levels excised was 1.6 (range, 1-5). Total EBL
      averaged 1317 mL (range, 50-6026 mL). Eleven patients were excluded: 7 with
      incomplete data and 4 who received aminocaproic acid (too few to compare). This
      resulted in 136 cases; 64 with no AF, 42 received TXA, and 30 received aprotinin.
      Overall %BV/level EBL was 41% +/- 39% (range, 6%-162%) and was significantly
      higher in the no-AF group (52% +/- 37%) than the TXA (30% +/- 34%; P < 0.01) and
      aprotinin (32% +/- 24%; P < 0.05) groups. The effect of the AFs varied by site.
      CONCLUSION: EBL associated with VCR was highly variable and in many cases
      exceeded the patient's BV. AF agents were not routinely used and we had
      insufficient data to assess the efficacy of aminocaproic acid. Both aprotinin and
      TXA resulted in less EBL than when no AF was used; however, the effect of the
      reduction varied by site. Aprotinin has since been removed from the market. When
      normalized to patient size and levels excised, the use of TXA resulted in a
      reduction in intraoperative EBL.

PMID- 22872218
TI  - Teriparatide accelerates lumbar posterolateral fusion in women with
      postmenopausal osteoporosis: prospective study.
AB  - STUDY DESIGN: Prospective trial. OBJECTIVE: To examine the clinical efficacy of
      teriparatide for bone union after instrumented lumbar posterolateral fusion using
      local bone grafting in women with postmenopausal osteoporosis. SUMMARY OF
      BACKGROUND DATA: Intermittent parathyroid hormone (PTH) treatment increases bone
      mass and reduces the risk for osteoporotic vertebral fractures. Recombinant human
      PTH (1-34) has already been approved as a treatment for severe osteoporosis.
      Preclinical data support the efficacy of PTH for lumbar spinal fusion. However,
      clinical results of PTH for spinal fusion have not yet been reported. METHODS:
      Fifty-seven women with osteoporosis diagnosed with degenerative spondylolisthesis
      were divided into 2 treatment groups, a teriparatide group (n = 29; daily
      subcutaneous injection of 20 MUg of teriparatide) and a bisphosphonate group (n =
      28; weekly oral administration of 17.5 mg of risedronate). All patients underwent
      decompression and 1- or 2-level instrumented posterolateral fusion with a local
      bone graft. Fusion rate, duration of bone union, and pain scores were evaluated 1
      year after surgery. RESULTS: Pain scores improved after surgery; however, no
      significant difference was noted between the groups after surgery. The rate of
      bone union was 82% in the teriparatide group and 68% in the bisphosphonate group.
      Average duration of bone union was 8 months in the teriparatide group and 10
      months in the bisphosphonate group. The rate of bone union and average of
      duration of bone union in the teriparatide group patients were significantly
      superior to those in the bisphosphonate group. CONCLUSION: Daily subcutaneous
      injection of teriparatide for bone union using local bone grafting after
      instrumented lumbar posterolateral fusion in women with postmenopausal
      osteoporosis was more effective than oral administration of bisphosphonate.

PMID- 22872219
TI  - Indication for spinal fusion and the risk of adjacent segment pathology:  does
      reason for fusion affect risk? A systematic review.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: To determine whether different
      indications or reasons for spinal fusion are associated with different risks of
      subsequent adjacent segment pathology (ASP) in the lumbar and cervical spine.
      SUMMARY OF BACKGROUND DATA: Pre-existing degeneration at levels adjacent to an
      arthrodesis may play a role in the development of symptomatic adjacent segment
      pathology. Although most spinal arthrodeses occur in patients with degenerative
      spinal disease, spinal fusion occurs in the pediatric and trauma population, and
      also congenitally. Evaluating the risk of ASP in these populations may shed light
      on its etiology. METHODS: A systematic search was conducted in PubMed and the
      Cochrane Library for articles published between January 1, 1990, and December 31,
      2011. We included all articles that described the risk of radiographical adjacent
      segment pathology (RASP) following surgical fusion for degenerative disease, for
      trauma, or for conditions requiring fusion in pediatrics in the lumbar or
      cervical spine. In addition, we included studies recording ASP in patients with
      congenital fusion. RESULTS: Nineteen studies met our inclusion criteria. In
      patients who underwent fusion in the lumbar spine for degenerative reasons, the
      RASP rate averaged 12.4% during an average of 5.6-year follow-up. For patients
      who underwent fusion in the cervical spine for degenerative reasons, the average
      RASP rate was 25.3% during a 2.3-year follow-up. For patients with Klippel-Feil
      syndrome and congenital fusion, the RASP rate averaged 49.7% during an average of
      23.5-years of follow-up. In patients who were fused for scoliosis, the average
      RASP rate was 20.3% of 3.9-year follow-up. However there is significant variation
      between studies in patient population, follow-up, and definition of RASP.
      CONCLUSION: In the cervical spine, the rate of RASP in patients with fusion for
      degenerative reasons indications is greater than the rate of RASP in patients
      with congenital fusion suggesting that the pre-existing health and status of the
      adjacent level at the time of fusion may play a contributory role in the
      development of ASP. There is insufficient evidence in the literature to determine
      whether the indication/reason for fusion affects the risk of RASP in the lumbar
      spine CONSENSUS STATEMENT: In the cervical spine, the rate of RASP in patients
      with fusion for degenerative reasons indications is greater than the rate of RASP
      in patients with congenital fusion suggesting that the pre-existing health and
      status of the adjacent level at the time of fusion may play a contributory role
      in the development of ASP. Strength of Statement: Weak.

PMID- 22872220
TI  - The natural history of degeneration of the lumbar and cervical spines: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the population risk of
      radiographical degeneration in the lumbar and cervical spine as well as the risk
      of adjacent segment pathology (ASP) among patients who receive and do not receive
      (but were eligible for) fusion for lumbar or cervical degeneration. SUMMARY OF
      BACKGROUND DATA: The etiology of ASP remains unclear. It has been suggested that
      ASP results because of a biomechanical stress transfer from the fusion. It has
      also been suggested that ASP is a continuation of natural arthritic disease. We
      sought to examine the literature and compare the rates of spinal degeneration
      without fusion and the rates of adjacent segment degeneration. Similarities or
      differences may yield insight into the etiology of ASP. METHODS: A systematic
      review of the English language literature was undertaken for articles published
      between 1990 and March 15, 2012. Electronic databases and reference lists of key
      articles were searched to identify articles reporting prevalence and/or incidence
      of radiographical spinal degeneration (de novo degeneration) or radiographical
      adjacent segment pathology (RASP) (degeneration after fusion). Two independent
      reviewers assessed the level of evidence and the overall quality of the
      literature using the Grades of Recommendation Assessment, Development and
      Evaluation criteria. Disagreements were resolved by consensus. RESULTS: We
      identified 15 studies from our search strategy that met the inclusion criteria
      from a total of 235 possible studies. Various definitions of radiographical
      spinal degeneration were used across the studies. For the population risk of
      radiographical lumbar and cervical spine degeneration, the cumulative incidence
      ranged from 12.7% to 51.5% during a 5- to 25-year period across 3 studies. One
      study of the cervical spine reported that there was a baseline prevalence of disc
      degeneration of 21.7% and, in their follow-up study, reported that 47.9% of
      individuals had evidence of progression of degeneration during a mean 5.8-year
      follow-up. The rate of progression per 100 person-years showed an age- and sex
      specific trend, with females progressing at a faster rate than males through the
      50s, males progressing faster than females during the 60s and 70s, with rates
      becoming identical in the 80s. Regarding age-specific risk, the prevalence of
      lumbar degeneration increased with age across 2 studies. For RASP following
      fusion, the cumulative incidence ranged from 6.3% to 44.4% during 6 to 12.6 years
      of follow-up across the 7 studies; the risk of cervical RASP was higher than that
      of lumbar despite the shorter mean follow-up periods. CONCLUSION: RASP may occur
      at a higher rate than natural history and suggests that another factor (such as
      biomechanical effect of fusion) may accelerate pathologic changes. CONSENSUS
      STATEMENT: ASP may occur at a higher rate than natural spinal degeneration and
      suggests that another factor (such as biomechanical effect of fusion) may
      accelerate pathologic changes. Strength of Statement: Weak.

PMID- 22872221
TI  - Do lumbar motion preserving devices reduce the risk of adjacent segment pathology
      compared with fusion surgery? A systematic review.
AB  - STUDY DESIGN: A systematic review of the literature. OBJECTIVE: To compare total
      disc replacement (TDR) with fusion, other motion-sparing devices with fusion, and
      motion-sparing devices with other motion-sparing devices to determine which
      devices may be associated with a lower risk of radiographical or clinical
      adjacent segment pathology (ASP). SUMMARY OF BACKGROUND DATA: Adjacent segment
      pathology, also termed adjacent segment disease (ASD) or adjacent segment
      degeneration, is a controversial phenomenon that can occur after a spinal fusion;
      it is thought to be either related to the altered mechanics or loss of motion
      from the fusion or to be part of the natural history of progressive arthritis.
      Motion preservation devices theoretically may decrease or prevent ASP from
      occurring. METHODS: A systematic search was conducted in PubMed and the Cochrane
      Library for literature published between January 1990 and February 2012. For all
      key questions, we identified all cohort studies and randomized controlled trials,
      making the comparison of interest independent of the outcomes measured. We
      searched each full-text article to determine whether it reported any type of
      structural or degenerative condition specifically occurring at an adjacent
      segment. We included articles reporting adult lumbar patients who had
      degenerative disc disease, disc herniation, radiculopathy, kyphosis, scoliosis,
      and spondylolisthesis, and who were treated with TDR, other motion-sparing
      procedures, or fusion. The overall strength of the evidence for each key question
      was rated using the Grades of Recommendation Assessment, Development and
      Evaluation (GRADE) criteria. RESULTS: There is moderate evidence to suggest that
      patients who undergo fusion may be nearly 6 times more likely to be treated for
      ASP than those who undergo TDR. From 2 randomized trials, the pooled risk of
      clinical ASP treated surgically was 1.2% and 7.0% in the TDR and fusion groups,
      respectively (P = 0.009). The increased risk of clinical ASP treated surgically
      associated with fusion is 5.8%. For every 17 operations, one might expect a new
      clinical ASP event requiring surgery when treated with fusion in those otherwise
      not harmed by TDR. There was insufficient literature to answer the other key
      questions, resulting in low to insufficient evidence that other motion-sparing
      operations are superior to fusion in preventing clinical ASP. CONCLUSION: There
      does seem to be a low rate of ASP after lumbar spinal fusion. The evidence
      suggests that the risk of clinical ASP following fusion is higher when compared
      with TDR, but there is limited evidence that fusion may increase the risk of
      developing clinical ASP compared with other motion-sparing procedures. CONSENSUS
      STATEMENT: 1. Evidence demonstrates that the risk of clinical ASP requiring
      surgery is likely greater after fusion but the risk is still quite rare. The
      increased risk compared to TDR could be as small as less than 1% or as great as
      10%. Strength of Statement: Weak. 2. There is insufficient evidence to make a
      definitive statement regarding fusion versus other motion-sparing devices with
      respect to the risk of ASP.

PMID- 22872222
TI  - Adjacent segment pathology following cervical motion-sparing procedures or
      devices compared with fusion surgery: a systematic review.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: To critically review and summarize
      the literature comparing motion preservation devices to fusion in the cervical
      spine to determine whether the use of these devices decreases the development of
      radiographical (RASP) or clinical adjacent segment pathology (CASP) compared with
      fusion. SUMMARY OF BACKGROUND DATA: Historically, surgical treatment of
      symptomatic cervical disc disease presenting as radiculopathy and/or myelopathy
      with anterior cervical decompression and fusion has yielded excellent results.
      Controversy remains whether RASP and CASP requiring treatment is due to fusion
      altered biomechanics and kinematics versus natural history. METHODS: We conducted
      a systematic search in MEDLINE and the Cochrane Collaboration Library for
      literature published through February 2012 on human randomized control trials or
      cohort studies published in the English language containing abstracts to answer
      the following key questions: (1) Is there evidence that total disc replacement
      (TDR) is associated with a lower risk of RASP or CASP compared with fusion? (2)
      Is there evidence that other procedures that do not involve arthrodesis or other
      motion-sparing devices are associated with a lower risk of RASP or CASP compared
      with fusion? (3)Is one type of motion preservation device or procedure associated
      with a lower risk of RASP or CASP compared with others? RESULTS: The initial
      literature search yielded 276 citations, of which 73 unique, potentially relevant
      citations that were evaluated against the inclusion/exclusion criteria set a
      priori. A total of 14 studies were selected for inclusion. For question 1, RASP
      was variably reported in studies that compared total disc replacement (TDR) to
      anterior cervical decompression and fusion (ACDF), and risk differences for
      reoperation due to CASP ranged from 1.0% to 4.8%, with no statistically
      significant differences between groups. For question 2, no studies comparing
      motion preservation devices to ACDF met our inclusion criteria. For question 3,
      one study comparing motion-sparing devices found the risk of RASP to be similar
      between groups. CONCLUSION: A paucity of high-quality literature comparing motion
      preserving devices or treatment methods to fusion or other motion-preserving
      techniques or devices (with RASP and/or CASP as an outcome using consistent
      definitions) exists. Independently funded, blinded long-term follow-up
      prospective studies would be able to delineate the true effects regarding
      incidence of RASP and CASP and treatment of CASP. CONSENSUS STATEMENT: 1. There
      is no significant difference in development of RASP and CASP after C-TDR versus
      ACDF at short- to mid-term follow-up. LEVEL OF EVIDENCE: Moderate. Strength of
      Statement: Strong. Recommendation 1: No recommendation can be made from
      comparative literature of nonarthroplasty motion preservation device or
      techniques compared with fusion regarding the risk of RASP or CASP. LEVEL OF
      EVIDENCE: Insufficient. Strength of Statement: Strong. Recommendation 2: No
      recommendation can be made from direct comparative literature of various motion
      preservation devices or techniques regarding the risk of RASP or CASP. LEVEL OF
      EVIDENCE: Insufficient. Strength of Statement: Strong.

PMID- 22872223
TI  - The risk of adjacent-level ossification development after surgery in the cervical
      spine: are there factors that affect the risk? A systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To answer the following clinical
      questions: (1) What is the risk of adjacent-level ossification development (ALOD)
      in patients receiving noninstrumented cervical fusion, instrumented cervical
      fusion with a plate, or cervical total disc arthroplasty?; (2) What are the risk
      factors for ALOD?; (3) What is the time course for the development of ALOD?; and
      (4) Does ALOD affect outcomes and rates of reoperation? SUMMARY OF BACKGROUND
      DATA: Anterior cervical plating, total disc arthroplasty, and noninstrumented
      fusion have all been used in the treatment of cervical disc disease. There are
      numerous reports that identify ALOD, a form of heterotopic ossification, as a
      major risk factor after performing these procedures. Few studies have compared
      these 3 procedures to evaluate the risk, timing, and outcomes related to
      postoperation ALOD. METHODS: A systematic search was conducted in PubMed and the
      Cochrane Library for articles published between January 1, 1990, and December 31,
      2011. We included all articles that described the risk of or risk factors for
      ALOD after surgical treatment of the cervical spine. Studies with patients older
      than 18 years or those treated for tumor or trauma were excluded from the study.
      In addition, those with posterior fusions, case reports, and case series with
      less than 10 patients were excluded. RESULTS: A total of 5 studies met the
      inclusion criteria for our systematic review. The risk of ALOD with anterior
      cervical discectomy and fusion ranged from 41% to 64%, whereas the risk of ALOD
      after total disc replacement ranged from 6% to 24%. When ALOD did occur, there
      was a 2-fold higher risk of development at the cranial adjacent segment. The most
      important risk factor for the development of ALOD was the use of instrumentation
      and the plate-to-disc distance, although the surgical procedure type (corpectomy
      vs. discectomy and fusion) neared but did not reach statistical significance.
      Insufficient evidence was available to delineate the time course for its
      development and how ALOD affected outcomes. CONCLUSION: The current body of
      literature suggests that ALOD will develop with the use of instrumentation and
      especially so if anterior instrumentation is placed within 5 mm of the adjacent
      cranial disc segment. In addition, total disc replacement showed lower rates for
      the development of ALOD compared with anterior cervical discectomy and fusion at
      both short- and long-term follow-up. CONSENSUS STATEMENT: We recommend that the
      surgeon make every effort to keep the plate as far away from the adjacent disc as
      possible. Strength of Statement: Strong.

PMID- 22872224
TI  - Methodology for the systematic reviews on an adjacent segment pathology.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: To provide a detailed description
      of the methods undertaken in the systematic search and analytical summary of
      adjacent segment pathology (ASP) issues and to describe the process used to
      develop consensus statements and clinical recommendations regarding factors
      associated with the prevention and treatment of ASP. SUMMARY OF BACKGROUND DATA:
      We present methods used in conducting the systematic, evidence-based reviews and
      development of expert panel consensus statements and clinical recommendations on
      the classification, natural history, risk factors, and treatment of
      radiographical and clinical ASP. Our intent is that clinicians will combine the
      information from these reviews with an understanding of their own capacities and
      experience to better manage patients at risk of ASP and consider future research
      for the prevention and treatment of ASP. METHODS: A systematic search and
      critical review of the English-language literature was undertaken for articles
      published on the classification, risk, risk factors, and treatment of
      radiographical and clinical ASP. Articles were screened for relevance using a
      priori criteria, and relevant articles were critically reviewed. Whether an
      article was included for review depended on whether the study question was
      descriptive, one of therapy, or one of prognosis. The strength of evidence for
      the overall body of literature in each topic area was determined by 2 independent
      reviewers considering risk of bias, consistency, directness, and precision of
      results using a modification of the Grades of Recommendation Assessment,
      Development and Evaluation (GRADE) criteria. Disagreements were resolved by
      consensus. Findings from articles meeting inclusion criteria were summarized.
      From these summaries, consensus statements or clinical recommendations were
      formulated among subject experts through a modified Delphi process using the
      GRADE approach. RESULTS: A total of 3382 articles were identified and screened on
      14 topics relating to the classification, risks, risk factors, and treatment of
      radiographical and clinical ASP. Of these, 127 met our predetermined inclusion
      criteria and were used to answer specific clinical questions within each topic.
      Lack of precision in the terminology related to adjacent segment disease and
      critical evaluation of definitions used across included articles led to a
      consensus to use ASP and suggest it as a standard. No validated comprehensive
      classification system for ASP currently exists. The expert panel developed a
      consensus definition of radiographical and clinical ASP (RASP and CASP). Some of
      the highlights from the analyses included the annual, 5- and 10-year risks of
      developing cervical and lumbar ASP after surgery, several important risk factors
      associated with the development of cervical and lumbar ASP, and the possibility
      that some motion sparing procedures may be associated with a lower risk of ASP
      compared with fusion despite kinematic studies demonstrating similar adjacent
      segment mobility following these procedures. Other highlights included a high
      risk of proximal junctional kyphosis (PJK) following long fusions for deformity
      correction, postsurgical malalignment as a potential risk factor for RASP and the
      paucity of studies on treatment of cervical and lumbar ASP. CONCLUSION:
      Systematic reviews were undertaken to understand the classification, risks, risk
      factors, and treatment of RASP and CASP and to provide consensus statements and
      clinical recommendations. This article reports the methods used in the reviews.

PMID- 22872225
TI  - Biomechanical effects of disc degeneration and hybrid fixation on the transition
      and adjacent lumbar segments: trade-off between junctional problem, motion
      preservation, and load protection.
AB  - STUDY DESIGN: The biomechanical effects of disc degeneration and hybrid fixation
      on the transition and adjacent segments were evaluated using a numerical
      approach. OBJECTIVE: This study aimed to evaluate the rigidity-rising effects of
      the dehydrated disc and bridged fixator on the kinematic and mechanical
      redistribution of the transition and adjacent segments. SUMMARY OF BACKGROUND
      DATA: After static fixation, a dynamic fixator can be used to preserve motion and
      share loads for the transition segments. However, the hybrid use of both static
      and dynamic fixators and its effects on the biomechanical behavior of the
      transition and adjacent segments were not investigated extensively. METHODS: A
      nonlinear and osseoligamentous lumbar model from L1 vertebra to S1 vertebrae was
      developed. Ligament interconnection, muscular contraction, and weight compression
      were all used to simulate lumbar flexion. The static fixator was instrumented at
      the degenerative L4-L5 segment and the dynamic fixators (Dynesys system) with
      different stiffness were subsequently applied to the degenerative or healthy L3
      L4 segment. A healthy lumbar model was used as a reference point for further
      comparison and evaluation. The predicted results were validated with the
      cadaveric and numerical values of the literature studies. Among the 21 models,
      the junctional problem at the adjacent (L2/L3 and L5/S1) discs as well as the
      motion preservation and stress distribution at the transition (L3/L4) disc were
      compared. RESULTS: Static fixation and the degenerative disc deteriorated the
      junctional problem at adjacent segments. On average, the hybrid fixation of the
      original Dynesys cord constrained the range of motion (ROM) by 65%. Furthermore,
      it shared 43% of the stress on the transition disc. However, this resulted in the
      adjacent discs increasing about 50% ROM and 40% stress. The term "trade-off
      stiffness" was used to express the concept that the decreased stiffness of the
      original cord could balance the junctional problem, motion preservation, and load
      protection of the transition and adjacent segments. The trade-off stiffness of
      the degenerative transition disc was higher than that of the healthy disc.
      Compared with the original design, the increased ROM and stress of the adjacent
      segments can be reduced by about 43% using the trade-off stiffness. CONCLUSION:
      The use of the hybrid fixator should involve a certain trade-off between the
      protection of the transition segment and the deterioration of the adjacent
      segments. This trade-off stiffness, which largely depends on both fixator design
      and disc degeneration, provides the improved rigidity and flexibility of the
      transition and adjacent segments.

PMID- 22872226
TI  - Introduction/Summary statement: adjacent segment pathology.

PMID- 22872227
TI  - An orthotopic bladder tumor model and the evaluation of intravesical saRNA
      treatment.
AB  - We present a novel method for treating bladder cancer with intravesically
      delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder
      tumor model. The mouse model is established by urethral catheterization under
      inhaled general anesthetic. Chemical burn is then introduced to the bladder
      mucosa using intravesical silver nitrate solution to disrupt the bladder
      glycosaminoglycan layer and allows cells to attach. Following several washes with
      sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the
      catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder
      tumors is confirmed and monitored by in vivo bladder ultrasound and
      bioluminescent imaging. The tumors are then treated intravesically with saRNA
      formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with
      ultrasound and bioluminescence. All steps of this procedure are demonstrated in
      the accompanying video.

PMID- 22872229
TI  - Effectiveness of the Austrian disease management programme "Therapie Aktiv" for
      type 2 diabetes regarding the improvement of metabolic control, risk profile and
      guideline adherence: 2 years of follow up.
AB  - BACKGROUND: We evaluated the disease management programme (DMP) "Therapie Aktiv"
      for diabetes mellitus type 2 during the first year of implementation in a cluster
      randomised controlled trial (RCT), which revealed an improvement of process
      quality, but only insignificant effects on HbA1c. To further analyse the effects
      of the DMP we followed up participants of the RCT for another year. METHODS:
      After completion of the RCT, the study was continued as an open observational
      trial. By patient's choice, three groups were formed. Group 1 (DMP/DMP):
      interventions of the RCT (DMP), who remained in the DMP; group 2 (Control/DMP):
      controls of the RCT (usual care), who participated in the DMP during the second
      year; group 3 (Control/Control): controls of the RCT (usual care), who remained
      as controls. PRIMARY OUTCOME MEASURE: HbA1c. SECONDARY OUTCOME MEASURES: BMI,
      lipids, blood pressure and measures of process quality. RESULTS: Only 801 of
      1,489 RCT participants completed the study (53.8 %). Group 1: n = 355; group 2: n
      = 335; group 3: n = 111. After 2 years, pre-post-analysis revealed a significant
      reduction of HbA1c (0.37 %, p < 0.001) in both DMP groups, and a reduction of
      only 0.03 % (p = 0.975) in the control group. However, the difference between the
      groups was not significant (p = 0.065). There was a significant improvement of
      process quality in the DMP groups compared with controls. CONCLUSION: The DMP
      clearly enhances process quality. Furthermore, the DMP yields a reduction of
      HbA1c within groups after 2 years, but significance is lost in between-group
      analysis. We conclude that the DMP has only a minor effect on metabolic control.

PMID- 22872230
TI  - The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood
      volume with oxygen demand.
AB  - Given the brain's uniquely high cell density and tissue oxygen levels bordering
      on hypoxia, the ability to rapidly and precisely match blood flow to constantly
      changing patterns in neural activity is an essential feature of cerebrovascular
      regulation. Locus coeruleus-norepinephrine (LC-NE) projections innervate the
      cerebral vasculature and can mediate vasoconstriction. However, function of the
      LC-mediated constriction in blood-flow regulation has never been addressed. Here,
      using intrinsic optical imaging coupled with an anesthesia regimen that only
      minimally interferes with LC activity, we show that NE enhances spatial and
      temporal aspects of functional hyperemia in the mouse somatosensory cortex.
      Increasing NE levels in the cortex using an alpha(2)-adrenergic receptor
      antagonist paradoxically reduces the extent of functional hyperemia while
      enhancing the surround blood-flow reduction. However, the NE-mediated
      vasoconstriction optimizes spatial and temporal focusing of the hyperemic
      response resulting in a sixfold decrease in the disparity between blood volume
      and oxygen demand. In addition, NE-mediated vasoconstriction accelerated
      redistribution to subsequently active regions, enhancing temporal synchronization
      of blood delivery. These observations show an important role for NE in optimizing
      neurovascular coupling. As LC neuron loss is prominent in Alzheimer and Parkinson
      diseases, the diminished ability to couple blood volume to oxygen demand may
      contribute to their pathogenesis.

PMID- 22872231
TI  - Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S
      donor sodium hydrosulfide in diabetic nephropathy.
AB  - BACKGROUND: Hydrogen sulfide (H(2)S) has recently been found to play beneficial
      roles in ameliorating several diseases, including hypertension, atherosclerosis
      and cardiac/renal ischemia-reperfusion injuries. Cystathionine beta-synthase
      (CBS) and cystathionine gamma-lyase (CSE), the main enzymes in the
      transsulfuration pathway, catalyze H(2)S production in mammalian tissues.
      However, the distributions and precise roles of these enzymes in the kidney have
      not yet been identified. METHODS: The present study examined the localization of
      both enzymes in the normal kidney and the effect of the H(2)S donor sodium
      hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of
      diabetic nephropathy, using pancreatic beta-cell-specific calmodulin
      overexpressing transgenic mice as a model of diabetes. RESULTS: In the normal
      kidney, we detected expression of both CBS and CSE in the brush border and
      cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and
      vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC
      diameter and blood flow. We further evaluated whether biosynthesis of H(2)S was
      altered in a spontaneous diabetic model that developed renal lesions similar to
      human diabetic nephropathy. CSE expression was markedly reduced under diabetic
      conditions, whereas CBS expression was unaffected. Progressive diabetic
      nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was
      ameliorated by NaHS treatment. CONCLUSION: These findings suggest that CSE
      expression in the proximal tubules may also regulate tubulointerstitial
      microcirculation via H(2)S production. H(2)S may represent a target of treatment
      to prevent progression of ischemic injury in diabetic nephropathy.

PMID- 22872232
TI  - Ranolazine-induced postrepolarization refractoriness suppresses induction of
      atrial flutter and fibrillation in anesthetized rabbits.
AB  - Ranolazine (Ran) is a novel anti-ischemic agent with electrophysiologic
      properties mainly attributed to the inhibition of late Na(+) current and atrial
      selective early Na(+) current. However, there are only limited data regarding its
      efficacy and mechanism of action against atrial flutter (Afl) and atrial
      fibrillation (AF) in intact animals. Therefore, we aimed to investigate the
      electrophysiologic mechanism of Ran in a rabbit model of inducible atrial
      tachyarrhythmias elicited by acetylcholine (ACh). Arrhythmias were produced in 19
      rabbits by rapid atrial burst pacing during control, after intravenous ACh and
      after Ran + ACh administration. Recording of right atrial monophasic action
      potentials (MAPs) and programmed stimulation were utilized to determine the
      duration of atrial repolarization at various cycle lengths and voltage levels of
      action potential, including 75% of total MAP duration (MAPD75), effective
      refractory period (ERP), and postrepolarization refractoriness (PRR = ERP -
      MAPD75) prior to and after Ran. Control stimulation yielded no arrhythmias or
      maximal nonsustained runs of Afl/AF. Upon ACh, 17 of 19 rabbits exhibited
      sustained Afl and AF as well as mixed forms of Afl/AF, while 2 animals revealed
      none or short runs of nonsustained arrhythmias and were excluded from the study.
      High-frequency burst pacing during the first 30 minutes after Ran + ACh failed to
      induce any arrhythmia in 13 of 17 rabbits (76%), while 2 animals displayed
      sustained Afl/AF and 2 other animals nonsustained Afl/AF. At basic stimulation
      cycle length of 250 milliseconds, Ran prolonged baseline atrial ERP (80 +/- 8 vs
      120 +/- 9 milliseconds, P < .001) much more than MAPD75 (65 +/- 7 vs 85 +/- 7
      milliseconds, P < .001), leading to atrial PRR which was more pronounced after
      Ran compared with control measurements (35 +/- 11 vs 15 +/- 10 milliseconds, P <
      .001). This in vivo study demonstrates that Ran exerts antiarrhythmic activity by
      suppressing inducibility of ACh-mediated Afl/AF in intact rabbits. Its action may
      predominantly be related to a significant increase in atrial PRR, resulting in
      depressed electrical excitability and impediment of arrhythmia initiation.

PMID- 22872233
TI  - Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown
      adipose tissue activity in humans.
AB  - Brown adipose tissue (BAT) is currently considered as a target to combat obesity
      and diabetes in humans. BAT is densely innervated by the sympathetic nervous
      system (SNS) and can be stimulated by beta-adrenergic agonists, at least in
      animals. However, the exact role of the beta-adrenergic part of the SNS in BAT
      activation in humans is not known yet. In this study, we measured BAT activity by
      2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) positron emission
      tomography/computed tomography imaging in 10 lean men during systemic infusion of
      the nonselective beta-agonist isoprenaline (ISO) and compared this with cold
      activated BAT activity. ISO successfully mimicked sympathetic stimulation as
      shown by increased cardiovascular and metabolic activity. Energy expenditure
      increased to similar levels as during cold exposure. Surprisingly, BAT was not
      activated during beta-adrenergic stimulation. We next examined whether the high
      plasma free fatty acid (FFA) levels induced by ISO competed with glucose
      ([(18)F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI).
      ACI successfully lowered plasma FFA, but did not increase [(18)F]FDG-uptake in
      BAT. We therefore conclude that systemic nonselective beta-adrenergic stimulation
      by ISO at concentrations that increase energy expenditure to the same extent as
      cold exposure does not activate BAT in humans, indicating that other tissues are
      responsible for the increased beta-adrenergic thermogenesis.

PMID- 22872234
TI  - Constitutive and inflammatory immunopeptidome of pancreatic beta-cells.
AB  - Type 1 diabetes is characterized by the autoimmune destruction of pancreatic beta
      cells. Recognition of major histocompatibility complex (MHC)-bound peptides is
      critical for both the initiation and progression of disease. In this study, MHC
      peptide complexes were purified from NIT-1 beta-cells, interferon-gamma (IFN
      gamma)-treated NIT-1 cells, splenic and thymic tissue of 12-week-old NOD mice,
      and peptides identified by mass spectrometry. In addition to global liquid
      chromatography-tandem mass spectrometry analysis, the targeted approach of
      multiple-reaction monitoring was used to quantitate the immunodominant K(d)
      restricted T-cell epitope islet-specific glucose-6-phosphatase catalytic subunit
      related protein (IGRP)206-214. We identified >2,000 MHC-bound peptides; 1,100 of
      these presented by beta-cells grown under normal conditions or after exposure to
      IFN-gamma. These include sequences from a number of known autoantigens.
      Quantitation of IGRP206-214 revealed low-level presentation by K(d) (~25
      complexes/cell) on NIT-1 cells after IFN-gamma treatment compared with the
      simultaneous presentation of the endogenously processed K(d)-restricted peptide
      Janus kinase-1355-363 (~15,000 copies/cell). We have successfully sequenced
      peptides from NIT-1 beta-cells under basal and inflammatory conditions. We have
      shown the feasibility of quantitating disease-associated peptides and provide the
      first direct demonstration of the disparity between presentation of a known
      autoantigenic epitope and a common endogenously presented peptide.

PMID- 22872235
TI  - Urinary proteomics for early diagnosis in diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a progressive kidney disease, a well-known
      complication of long-standing diabetes. DN is the most frequent reason for
      dialysis in many Western countries. Early detection may enable development of
      specific drugs and early initiation of therapy, thereby postponing/preventing the
      need for renal replacement therapy. We evaluated urinary proteome analysis as a
      tool for prediction of DN. Capillary electrophoresis-coupled mass spectrometry
      was used to profile the low-molecular weight proteome in urine. We examined urine
      samples from a longitudinal cohort of type 1 and 2 diabetic patients (n = 35)
      using a previously generated chronic kidney disease (CKD) biomarker classifier to
      assess peptides of collected urines for signs of DN. The application of this
      classifier to samples of normoalbuminuric subjects up to 5 years prior to
      development of macroalbuminuria enabled early detection of subsequent progression
      to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary
      albumin routinely used to determine the diagnosis (AUC 0.67). Statistical
      analysis of each urinary CKD biomarker depicted its regulation with respect to
      diagnosis of DN over time. Collagen fragments were prominent biomarkers 3-5 years
      before onset of macroalbuminuria. Before albumin excretion starts to increase,
      there is a decrease in collagen fragments. Urinary proteomics enables noninvasive
      assessment of DN risk at an early stage via determination of specific collagen
      fragments.

PMID- 22872236
TI  - Adiponectin enhances mouse fetal fat deposition.
AB  - Maternal obesity increases offspring birth weight and susceptibility to obesity.
      Adiponectin is an adipocyte-secreted hormone with a prominent function in
      maintaining energy homeostasis. In contrast to adults, neonatal blood adiponectin
      levels are positively correlated with anthropometric parameters of adiposity.
      This study was designed to investigate the role of adiponectin in maternal
      obesityenhanced fetal fat deposition. By using high-fat diet-induced obese mouse
      models, our study showed that maternal obesity increased fetal fat tissue mass,
      with a significant elevation in fetal blood adiponectin. However, adiponectin
      gene knockout (Adipoq(-/-)) attenuated maternal obesity-induced high fetal fat
      tissue mass. We further studied the effects of fetal adiponectin on fetal fat
      deposition by using a cross breeding approach to create Adipoq(-/+) and Adipoq(-/
      ) offspring, whereas maternal adiponectin was null. Adipoq(-/+) offspring had
      more fat tissue mass at both birth and adulthood. Significantly high levels of
      lipogenic genes, such as sterol regulatory element-binding protein 1c and fatty
      acid synthase, were detected in the livers of Adipoq(-/+) fetuses. In addition,
      expression of genes for placental fatty acid transport was significantly
      increased in Adipoq(-/+) fetuses. Together, our study indicates that adiponectin
      enhances fetal fat deposition and plays an important role in maternal obesity
      induced high birth weight.

PMID- 22872238
TI  - The rewards of pediatric neurosurgery: presidential address: twenty-ninth annual
      meeting of the International Society for Pediatric Neurosurgery, October 18,
      2011, Goa, India.
AB  - The author relates how he ended up somewhat unexpectedly as a pediatric
      neurosurgeon and how fortunate he feels to have become a pediatric neurosurgeon.
      He reflects on his life and on the importance of trying to do one's best. He
      comments about the importance of listening, empathizing, and being compassionate
      as characteristics of the pediatric neurosurgeon and notes that by trying one's
      best to be a good pediatric neurosurgeon one adopts more of these characteristics
      by learning from patients and their parents. He discusses the many ways in which
      the practice of pediatric neurosurgery and his involvement in the International
      Society for Pediatric Neurosurgery have created meaning in his life, which has
      led to a feeling of happiness and fulfillment.

PMID- 22872239
TI  - Editorial.

PMID- 22872237
TI  - Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2
      mutations.
AB  - Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is
      characterized by the absence of adipocytes and development of severe insulin
      resistance. In the current study, we investigated the adipogenic defect
      associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived
      multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from
      controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes
      after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect
      using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect
      was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived
      MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell
      death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt
      activation, and overexpression of constitutively active Akt can partially restore
      lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic
      acid, phosphatidylinositol species, as well as the peroxisome proliferator
      activated receptor gamma (PPARgamma) inhibitor cyclic phosphatidic acid. The
      PPARgamma agonist pioglitazone partially rescued the adipogenic defect in CGL
      cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of
      the lipome, altering normal activation of phosphatidylinositol 3-kinase
      (PI3K)/Akt and PPARgamma pathways in the early stages of adipogenesis.

PMID- 22872240
TI  - Gene expression profiling in human craniosynostoses: a tool to investigate the
      molecular basis of suture ossification.
AB  - INTRODUCTION: Non-syndromic craniosynostoses (NSC) occur as isolated skull
      malformations due to the premature ossification of one (single-suture forms) or
      more (complex forms) calvarial sutures and represent the most frequent form of
      craniosynostosis worldwide. The etiology of NSC is still largely unknown as a
      genetic basis can be rarely demonstrated especially in single-suture forms. In
      these cases, during the prenatal/perinatal development of affected patients, only
      one suture undergoes a premature direct ossification within an otherwise
      physiologically grown skull. This could suggest that definite somatic
      alterations, possibly due to unclear environmental agents, occur locally at the
      site of premature suture fusion during skull development. A promising tool to
      investigate the molecular mechanisms that may orchestrate this event is the
      comparative analysis of suture- and synostosis-derived tissues and cells.
      PURPOSE: This review focuses on the different studies that attempted to clarify
      this issue using genome-wide microarray-based technologies for the comparative
      analysis of gene expression profiles. All relevant results have been
      comprehensively reviewed, possibly compared, and critically discussed.
      CONCLUSION: Due to the heterogeneity of the dataset available in the literature,
      a univocal CRS-associated molecular profile could not be deciphered. Most
      differentially expressed genes are found in different studies to be involved in
      extracellular matrix remodeling.

PMID- 22872241
TI  - Genetic basis of single-suture synostoses: genes, chromosomes and clinical
      implications.
AB  - BACKGROUND: Non syndromic craniosynostoses are the most frequent craniofacial
      malformations worldwide. They represent a wide and heterogeneous group of
      entities, in which the dysmorphism may occur in a single (simple forms) or in
      multiple sutures (complex forms). Simple forms present a higher birth prevalence
      and are classified according to the involved suture and to the corresponding
      abnormal cranial shape: scaphocephaly (SC; sagittal suture), trigonocephaly (TC;
      metopic suture), anterior plagiocephaly (unilateral coronal suture), posterior
      plagiocephaly (unilateral lambdoid suture). They occur commonly as sporadic
      forms, although a familiar recurrence is sometimes observed, suggesting a
      mendelian inheritance. The genetic causes of simple craniosynostosis are still
      largely unknown, as mutations in common craniosynostosis-associated genes and
      structural chromosomal aberrations have been rarely found in these cases. AIMS:
      This review is intended to dissect comprehensively the state-of-the art on the
      genetic etiology of single suture craniosynostoses, in the attempt to categorize
      all known disease-associated genes and chromosomal aberrations. Possible
      genotype/phenotype correlations are discussed as useful clues towards the
      definition of optimized clinical management flowcharts.

PMID- 22872242
TI  - Isolated sagittal craniosynostosis: definition, classification, and surgical
      indications.
AB  - Sagittal craniosynostosis (SC) remains the most common type of synostosis,
      accounting for about a half of all forms. It would result from a mesenchymal
      disorder involving the intramembranous ossification of the sagittal suture and
      leading to its early fusion. No specific data on the etiologic factors are
      currently available. The premature ossification of the sagittal suture can result
      in three main types of SC, according to the different segment prevalently
      involved: anterior, posterior, and complete SC. The diagnosis is easily obtained
      by clinical examination. However, a radiological work up (3D CT scan) may be
      necessary to rule out hidden venous or cranial anomalies possibly associated with
      most severe cases, or for the surgical planning. The most common indication for
      surgery is the improvement of the cosmetic appearance of the skull, since a
      cranial deformation may have a significant psychological impact on affected
      subjects. To relieve from raised intracranial pressure is a further indication to
      surgery. Although an increased intracranial pressure can be demonstrated in a
      minority of affected children at diagnosis, indeed, it can present later (usually
      after the second/third year of life) with chronic symptoms. The role of surgery
      in the preservation of cognitive functions in scaphocephalic patients does not
      seem to be relevant, since minor anomalies of the cerebral development associated
      with SC would occur independently from the cranial shape. On the other hand, the
      surgical correction may show a protective effect on some visual skills, like the
      ability to fix and follow, and the fixation shift.

PMID- 22872243
TI  - Atypical scaphocephaly: a review.
AB  - BACKGROUND AND PURPOSE: Sagittal craniosynostosis (SCS) is common and easily
      recognized and corrected surgically. However, rare cases of SCS are more complex:
      these associate closure of the metopic or delayed closure of the coronal suture,
      uni- or bilaterally. MATERIAL AND METHODS: We reviewed the available literature
      on atypical sagittal craniosynostosis (ASCS). We also reviewed retrospectively
      our series of SCS treated since 1980 and selected cases with simultaneous closure
      of the metopic (leptocephaly) or delayed closure of other sutures (plagiocephaly,
      oxycephaly, or Crouzon syndrome). RESULTS: ASCS is rare, representing <10 % of
      SCS. In our series, among 447 cases of SCS followed for a mean duration of 63.7
      months, we identified 22 cases of ASCS: 6 with leptocephaly, 9 with non-syndromic
      oxycephaly, 4 with Crouzon syndrome, and 3 with plagiocephaly. Fourteen patients
      required a second operation, either planned initially (severe leptocephaly) or
      because of brain compression. The actuarial incidence of ASCS requiring
      reoperation was 5.3 % of SCS at 10 years. After a mean follow-up of 113 months,
      morphological results in ASCS were grade 1 (no defect) in 5, grade 2 (mild
      defect) in 2, grade 3 (minor reoperation) in 3, and grade 4 (major reoperation)
      in 12; one patient had visual impairment, and two had learning difficulties.
      CONCLUSIONS: ACSC can be detected initially or occur with a delay in apparently
      standard SCS. Leptocephaly is a specific entity. Because of the implications on
      the management and risk for the patient, preoperative evaluation of patients with
      SCS with CT scanner and prolonged follow-up are necessary.

PMID- 22872244
TI  - Scaphocephaly correction with retrocoronal and prelambdoid craniotomies (Renier's
      "H" technique).
AB  - OBJECTIVE: The aim of this paper is to describe the surgical technique,
      originally devised by Dr. Renier which is currently used to treat children with
      scaphocephaly under 6 months of age at the Craniofacial Unit of Hopital Necker
      Enfants Malades (French National Referral Center for Faciocraniosynostosis),
      focusing on its advantages and limitations.

PMID- 22872245
TI  - Endoscopic technique for sagittal synostosis.
AB  - PURPOSE: This study aimed to present a 16-year experience of treating sagittal
      synostosis with endoscopic-assisted techniques and postoperative cranial orthotic
      therapy. In 1996, we introduced the use of endoscopes for the management of
      sagittal synostosis in four young infants. During the subsequent years, we have
      treated a total of 256 patients with great success and long-term follow-up.
      Presented herein are the techniques and results of such clinical experience.
      METHODS: A total of 256 patients with sagittal synostosis have been treated
      between May 1996 and April 2012. There were 187 males and 69 females. Mean age at
      time of surgery was 3.9 months. A wide-vertex craniectomy with bilateral barrel
      stave osteotomies of the temporal and parietal bones using small scalp incisions
      and endoscopic viewing techniques was performed. Instruments have been developed
      to assist with the operation. All patients were placed in postoperative molding
      cranial orthosis. RESULTS: Mean estimated blood loss was 27 cc. Mean transfusion
      rate was 7 %. Mean surgical time was 57 min. Mean length of stay was 1.1 days.
      Using cephalic index (CI) as an anthropometric measurement to judge head shape,
      our results were classified as excellent (CI>80), good (CI 80-70), or poor
      (CI<70). A total of 87 % were classified as excellent, 9 % as good, and 4 % as
      poor. CONCLUSIONS: Endoscopic-assisted management of sagittal synostosis is a
      safe, efficacious, and excellent option for treating this condition with long
      lasting, superb results. It is associated with minimal morbidity and
      complications and improved results over traditional procedures.

PMID- 22872246
TI  - Mini-invasive surgical technique for sagittal craniosynostosis.
AB  - INTRODUCTION: Several techniques are currently available for the surgical
      correction of sagittal craniosynostosis. The most recently introduced ones have
      been specifically designed to perform a mini-invasive approach in order to reduce
      the postoperative morbidity. Herein, the surgical steps of a personal, mini
      invasive technique used to decrease the impact of the surgical scar are
      described. SURGICAL TECHNIQUE: The traditional biparietal skull expansion is
      realized through two to six short skin linear incisions (2-3 cm long)
      strategically scattered over the scalp, which allow the surgeon to perform a wide
      sagittal synostectomy, linear craniectomies along the coronal and lambdoid
      sutures, and barrel stave osteotomies on the frontal and occipital bones, if
      needed. No special instruments or postoperative molding therapy is required.
      DISCUSSION: The main advantages of this technique are the poor visibility of the
      surgical scar, the reduction of the perioperative morbidity (blood transfusion,
      orbital edema, subcutaneous fluid collection), and the shortening of surgical
      times and postoperative hospitalization. The main limits are represented by the
      minor correction of the frontal bossing and the old age of children at surgery
      (no optimal results after 10-12 months of age).

PMID- 22872247
TI  - Spring-assisted correction of sagittal suture synostosis.
AB  - PURPOSE: The purpose of this study is to describe the technique and advantages
      and limitations of spring-assisted cranioplasty for sagittal suture synostosis.
      METHODS: Preliminary data are presented of the first 41 patients treated with
      this technique at our institution. RESULTS: The cephalic index was 75 after
      surgery and dropped to 74 one year after surgery. Mean blood loss of both
      procedures combined was 54 ml. CONCLUSION: Spring-assisted cranioplasty requires
      only two small incisions and is at least as effective as other techniques with
      respect to the cephalic index. Blood loss, operative time, and complication rate
      are reduced. The most important disadvantage is the need to remove the springs in
      a second intervention. A second drawback is that the expansion of the spring is
      not controllable after placement. This can be partially intercepted by adjusting
      the spring (or the craniotomy) to the patient's specific features.

PMID- 22872248
TI  - Hybrid surgery for scaphocephaly with distraction osteogenesis using skull
      expanders: technical note.
AB  - BACKGROUND: The authors described their surgical technique for scaphocephaly in
      relatively older infants who are 5 months old or over. The technique is a kind of
      hybrid of distraction osteogenesis utilizing skull expanders and a traditional
      cranial reconstruction procedure. SURGERY: The surgery usually consists of four
      procedures. The first is to make strip craniotomy over the superior sagittal
      sinus (SSS) from the major fontanelle to the minor one. The second is the
      occipital craniotomy for the occipital bossing. The occipital bone flap undergoes
      barrel stave osteotomy and is repositioned later. The third is placement of skull
      expander for distraction osteogenesis. Bidirectional small strip craniotomy is
      made along the coronal and lambdoid sutures, then transverse cutting is added to
      make a hinge point near the base of the parietal bone. Two to three skull
      expanders are placed crossing the SSS. The last procedure is radial-oriented
      osteotomy on the dorsal end of frontal bone to meet the elevated, expanded
      parietal bone. Skull expansion starts within a week with 5 mm/week base up to 20
      to 30 mm. Exposed shafts of the expander are cut at the end of skull expansion.
      DISCUSSION: Process of osteogenesis is followed at an outpatient clinic, and the
      expanders are removed 4 to 6 months later after confirming the sufficient
      ossification. An advantage of our procedure is that maximum skull expansion is
      possible with minimum regression after distraction osteogenesis in the long term.
      Limited craniotomy enables limited blood loss. The skin trouble caused by
      stretching can be avoided. No postoperative helmet is required. A disadvantage is
      that the procedure leaves a foreign body on the skull for several months and
      requires additional surgery for removal.

PMID- 22872250
TI  - Anterior fronto-orbital remodeling for trigonocephay.
AB  - INTRODUCTION: Trigonocephaly secondary to the premature fusion of the metopic
      synostosis is associated to a risk of cerebral compression and several
      craniofacial morphological alterations. Numerous surgical techniques have been
      proposed. They all carry a risk of secondary temporal hollowing PURPOSE: The aim
      of this paper is to describe the surgical technique used for trigonocephaly at
      the craniofacial unit of Hopital Necker Enfants Malades (French National Referral
      Center for Faciocraniosynostosis) focusing on its advantages and limitations.
      Resorbable osteosynthesis should be part of the current techniques.

PMID- 22872249
TI  - Metopic synostosis.
AB  - Premature closure of the metopic suture results in a growth restriction of the
      frontal bones, which leads to a skull malformation known as trigonocephaly. Over
      the course of recent decades, its incidence has been rising, currently making it
      the second most common type of craniosynostosis. Treatment consists of a
      cranioplasty, usually preformed before the age of 1 year. Metopic synostosis is
      linked with an increased level of neurodevelopmental delays. Theories on the
      etiology of these delays range from a reduced volume of the anterior cranial
      fossa to intrinsic malformations of the brain. This paper aims to provide an
      overview of this entity by giving an update on the epidemiology, etiology,
      evolution of treatment, follow-up, and neurodevelopment of metopic synostosis.

PMID- 22872251
TI  - The Christmas tree foreheadplasty: a novel technique used in combination with a
      bandeau for fronto-orbital remodelling in craniosynostosis.
AB  - PURPOSE: Craniosynostosis of the coronal, metopic and frontosphenoidal sutures
      results in deformity of the forehead. This may cause both functional and
      psychological difficulties for patient and parent. We describe a novel surgical
      technique, the 'Christmas tree foreheadplasty', used in combination with a
      supraorbital bandeau to achieve fronto-orbital remodelling. METHODS: Between
      November 2008 and September 2011, 32 patients with craniosynostosis underwent
      fronto-orbital remodelling with a supraorbital bandeau in combination with
      Christmas tree foreheadplasty. Indications for surgery, age at surgery, blood
      transfusion requirements, length of hospital stay and perioperative complications
      were assessed. A 'blinded', independent reviewer, age-matched controlled, panel
      photograph study was also undertaken to review results of the surgery. A parental
      satisfaction survey by telephone questionnaire was undertaken. RESULTS: Mean age
      at surgery was 16 months. Average hospital stay was 3 days. Mean follow up time
      to this report was 19.5 months. Indications for the procedure included
      unicoronal, frontosphenoidal, metopic and bicoronal synostosis. Thirty of the 32
      patients required a blood transfusion. One patient has required revision surgery
      following extrusion of prosthetic fixation plate. Surgical outcome measured by
      'blinded' independent reviewers indicated that a significantly different
      preoperative score from normal was rendered to no significant difference from age
      matched normal controls postoperatively. Parental satisfaction score of forehead
      appearance was significantly improved by the technique. CONCLUSION: The Christmas
      tree foreheadplasty is a commendable and reproducible technique for forehead
      remodelling in combination with supraorbital bandeau and is now used more widely
      for forehead reconstruction for congenital cases.

PMID- 22872252
TI  - Endoscopic-assisted treatment of trigonocephaly.
AB  - Minimally invasive, endoscopic repair of metopic craniosynostosis has emerged as
      a potentially efficacious, safe, and aesthetically acceptable alternative to open
      procedures. Potential advantages of an early endoscopic approach to repair
      metopic craniosynostosis include a reduction in blood loss and consequent
      decreases in transfusion volumes, decreased hospital costs, shorter operative
      times, and limited duration of hospitalization. Other benefits of minimally
      invasive techniques would be avoidance of anaesthetic surgical scarring, decrease
      in postoperative swelling and discomfort, and lower rate of complications such as
      duramater tears, postoperative hyperthermia, or infection. However, a concern is
      usually raised about the achievements of the "endoscopic" techniques when
      compared to "standard" open approaches. The indications for endoscopic-assisted
      surgery in the treatment of trigonocephaly remain controversial and further
      series and follow-up of these patients are necessary to set up the role of these
      approaches.

PMID- 22872253
TI  - Posterior plagiocephaly.
AB  - INTRODUCTION: Asymmetrical cranial vaults resulting from external forces on an
      infant's head can be caused by abnormal sutural development (synostotic
      plagiocephaly) or abnormal external forces acting on an intrinsically normal,
      developing cranium (deformational plagiocephaly). DISCUSSION: The incidence of
      posterior plagiocephaly has increased dramatically since the initiation of the
      "Back to Sleep" campaign against sudden infant death syndrome. The majority of
      cases are due to deformational plagiocephaly, but rigorous diagnostic evaluation
      including physical examination and radiological imaging must be undertaken to
      rule out lambdoid synostosis in extreme or refractory cases. CONCLUSION: Unique
      clinical features and radiological examination using computed tomography
      technology are helpful in confirming the correct cause of posterior
      plagiocephaly. Plagiocephaly is considered a benign condition, but with the
      recent increase in cases, new studies have revealed developmental problems
      associated with cranial vault asymmetries. Treatment of positional/deformational
      plagiocephaly includes conservative measures, primarily behavior modification,
      and, in some cases, helmet therapy, whereas lambdoid synostotic plagiocephaly
      requires surgical intervention, making differentiation of the cause of the
      asymmetry critical.

PMID- 22872254
TI  - Posterior remodeling flap for posterior plagiocephaly.
AB  - INTRODUCTION: Nonsynostotic posterior plagiocephaly has become the most common
      skull deformation since pediatricians have suggested the supine position for the
      newborns to reduce the risk of sudden death. Prevention of such a "positional"
      deformation or its management once it has occurred is mainly based on physical
      maneuvers such as physiotherapy and active positional corrective measures.
      SELECTION CRITERIA: Surgical correction, however, may be suggested in rare cases
      where deformation of the skull is so severe or the referral of the child is so
      late that physical corrective treatment cannot be taken into consideration.
      Surgical management is based on the creation of a posterior bone flap to be
      repositioned after the opportune contouring and rotation. PURPOSE: The aim of
      this paper is to describe the surgical technique used for posterior vault
      remodeling in posterior plagiocephaly at the craniofacial unit of Hopital Necker
      Enfants Malades (French National Referral Center for Faciocraniosynostosis)
      focusing on its advantages and limitations.

PMID- 22872255
TI  - Craniosynostosis: posterior two-third cranial vault reconstruction using
      bioresorbable plates and a PDS suture lattice in sagittal and lambdoid
      synostosis.
AB  - INTRODUCTION: Beginning in 2004, we modified our surgical technique for a cranial
      vault remodeling in sagittal and lambdoid synostosis. Beginning in the early
      1990s, we started using a calvarial vault remodeling technique in sagittal and
      lambdoid synostosis that involves removing the posterior two thirds of the skull,
      extending from the coronal suture to below the lambdoid suture to within 1-1.5 cm
      of the foramen magnum. Up until 2004, the bone fixation evolved from wire
      fixation, then micro-metallic fixation plates and resorbable sutures. DISCUSSION:
      Over the last 9 years, we have used a novel technique of absorbable fixation
      plates and a polydioxanone suture trellis or lattice network, which has reduced
      operating times significantly and continued to give excellent results. Additional
      advantages include the absence of a need for molding or protective helmets, the
      absence of bony defects at the completion of the procedure, the absence of age
      limitation, and the ability to correct the tightly constricted occiput.
      CONCLUSION: To date, we have had no significant complications, no return to
      operating room, and the aesthetics have held up well since its introduction.

PMID- 22872256
TI  - Deformational plagiocephaly and orthotic treatment: indications and limitations.
AB  - PURPOSE: As the incidence of deformational plagiocephaly (DP) has risen, so has
      the demand on clinicians to make appropriate treatment recommendations. While
      knowledge of risk factors and natural history continue to evolve, there is
      uncertainty and controversy regarding intervention approaches. The purpose of
      this report is to review current treatment approaches for DP, in particular the
      use of orthotic helmets. METHODS: A narrative literature review was conducted to
      summarize current evidence supporting preventative measures and re-positional and
      orthotic interventions. RESULTS: When started early at under 2 months of age,
      positional efforts and 'tummy time' can be effective in preventing and improving
      DP, but these strategies need to be better promoted to caregivers. The timing,
      severity and parental concerns as indicators for orthotic treatment are reviewed.
      Limitations discussed include high cost, lower level of evidence and poor
      understanding of long-term outcomes and caregiving implications. CONCLUSION: For
      optimal outcome, current evidence supports use of repositioning in young infants
      and start of orthotic helmet treatment for infants with significant DP at 4-6
      months. Further research is needed to better understand the parameters for use
      (stratified by age and severity), long-term outcomes and natural history and the
      impact on caregiving, as well as the cultural significance of head shape.

PMID- 22872257
TI  - Anterior plagiocephaly: epidemiology, clinical findings,diagnosis, and
      classification. A review.
AB  - INTRODUCTION: Anterior plagiocephaly due to the early unilateral fusion of the
      coronal suture is associated to a clinical phenotype characterized by the
      unilateral flattening of the frontal bone and the orbit and by the distortion and
      maldevelopment of adjacent cranial and facial bones. Homolateral anterior
      displacement of the ear and contralateral deviation of the nasal pyramid and
      mandible are other prominent clinical features. The differential diagnosis
      includes a variety of conditions characterized by facial asymmetry, namely, due
      to muscular alterations, anomalies of the visual function, congenital anomalies
      of the cervical spine and craniovertebral junction, abnormal pregnancy, and birth
      injuries. Anterior plagiocephaly is the direct cause of oculomotor anomalies,
      with a characteristic strabismus, and of progressive asymmetrical maldevelopment
      of the face, craniovertebral junction, and cervical spine. METHODS: The medical
      literature was reviewed in regard to the epidemiology, clinical features, and
      radiological findings. Different categorization of the affected infants in
      specific subtypes according to the severity of the condition was analyzed. The
      aim was to contribute to a practical clinical classification to be utilized for
      the surgical indication and for predicting the prognosis according to the
      severity of the condition at presentation. CONCLUSIONS: Anterior plagiocephaly
      represents the most challenging simple suture craniosynostosis. The clinical
      differential diagnosis with other forms of cranial asymmetry is possible on the
      grounds of mere clinical findings. A classification system is necessary not only
      for the establishment of surgical planning but also to predict the late cosmetic
      and functional outcomes.

PMID- 22872258
TI  - Frontal-orbital advancement for the management of anterior plagiocephaly.
AB  - PURPOSES: The main purposes of this manuscript are to provide an overview of
      various modalities of surgical correction of anterior plagiocephaly and to
      emphasize their differences with the classic open frontal-orbital advancement.
      METHODS AND RESULTS: Advancement of technology provides development of many other
      ways to achieve the same results. The authors describe the classic open frontal
      orbital advancement and compare with other proposed techniques for correction of
      frontal plagiocephaly. The main limitation of the use of new forms of treatment
      of the anterior plagiocephaly is the age of the patient. There is still no
      consensus on criteria for quantitative evaluation of surgical results, and new
      forms of treatment do not present results with long follow-up. CONCLUSION:
      Frontal-orbital advancement is the preferred procedure to correct unicoronal
      synostosis due to its universal indication regardless of the age and degree of
      deformation of the anterior plagiocephaly.

PMID- 22872259
TI  - Endoscopic technique for coronal synostosis.
AB  - PURPOSE: This paper aims to present a 15-year experience treating coronal
      craniosynostosis with endoscopic-assisted techniques and postoperative cranial
      orthotic therapy. METHODS: A total of 100 patients with coronal craniosynostosis
      were treated between 1996 and 2010. There were 36 males and 64 females. A single
      2-cm incision was made halfway between anterior fontanelle and the squamosal on
      the affected side. Using endoscopic-assisted visualization, a strip of bone was
      removed between the aforementioned points. Following surgery, all patients were
      placed in cranial orthoses to assist in the correction of the craniofacial
      deformity. RESULTS: Mean estimated blood loss was 20 cm(3); only one patient
      required a transfusion. Mean length of stay was 1 day. Mean surgery time was 54
      min. There were no mortalities. There was significant correction of vertical
      dystopia (66 % from baseline) and midsagittal plane deviation (80 % from
      baseline). CONCLUSIONS: Endoscopic-assisted craniectomy for treatment of coronal
      craniosynostosis in very young infants followed by cranial molding is associated
      with excellent long-lasting results and minimal morbidity and no mortality.

PMID- 22872260
TI  - Unicoronal synostotic plagiocephaly: surgical correction: Lille's technique.
AB  - INTRODUCTION: For 35 years, we have a tight neuro-plastic surgical cooperation
      for the surgical correction and long-term systematic follow-up of 125 cases of
      unicoronal synostotic plagiocephaly. METHODS: We have tried to understand why
      some patients had kept an asymmetrical facial growth pattern in spite of a good
      fronto orbital correction. Analysis in vestibular orientation which was available
      from 1993 has demonstrated a discrepancy between the ocular and the vestibular
      verticality referential system. So we have designed a surgical procedure to try
      to fix that problem. RESULTS AND CONCLUSION: Preliminary results in 27 cases
      operated according to this procedure, for which we have pre- and post-CT scan
      demonstrate significative improvements of our results.

PMID- 22872261
TI  - Non-syndromic oxycephaly and brachycephaly: a review.
AB  - BACKGROUND: Non-syndromic coronal synostoses oxycephaly and brachycephaly
      (NSCSOB) are rare. Their natural history, surgical management, and outcome are
      debated. MATERIAL AND METHODS: We reviewed the available literature on NSCSOB. In
      addition, we reviewed retrospectively our experience with cases of NSCSOB,
      managed and operated by our joint craniofacial team since 1984. Newborns
      underwent perifrontal craniectomy, while infants and older children underwent
      fronto-orbital advancement with frontoparietal remodeling. Cases with delayed
      onset of faciosynostosis were excluded. RESULTS: Some cases of NSCSOB present at
      birth or even prenatally with gross dysmorphism and severe brachycephaly; others
      present later in life with harmonious restriction of intracranial volume and are
      at risk for development and vision. Some NSCSOB evolve from initially unisutural
      synostoses. We treated 61 cases, operated aged 1.4 to 106.7 months, 30 with
      brachycephaly and 31 with oxycephaly. Twelve of these (19.7 %), had been treated
      initially for sagittal or unicoronal synostosis, and evolved into NSCSOB.
      Intracranial hypertension was present initially in 28 (45.9 %), with
      ophthalmological consequences in 13 (21.3 %) and mental retardation in 6 (9.6 %).
      No patient had hydrocephalus; only two had asymptomatic Chiari malformation. The
      mean postoperative follow-up was 113.6 months. At last control, 21 patients had
      developmental delay and 5 had visual impairment. CONCLUSIONS: NSCSOB are a
      complex entity. They have in common a high risk of severe intracranial
      hypertension and rare hydrodynamic complications. Genetic screening is necessary
      to assert their non-syndromic nature. Prolonged follow-up of all craniosynostoses
      is necessary because unisutural synostoses can evolve into NSCSOB, and NSCSOB can
      evolve into craniofaciosynostosis.

PMID- 22872262
TI  - Impact of genetics on the diagnosis and clinical management of syndromic
      craniosynostoses.
AB  - PURPOSE: More than 60 different mutations have been identified to be causal in
      syndromic forms of craniosynostosis. The majority of these mutations occur in the
      fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of
      syndromic craniosynostosis varies based on the particular causal mutation.
      Additionally, the diagnosis of a patient with syndromic craniosynostosis is based
      on the clinical presentation, signs, and symptoms. The understanding of the
      hallmark features of particular syndromic forms of craniosynostosis leads to
      efficient diagnosis, management, and long-term prognosis of patients with
      syndromic craniosynostoses. METHODS: A comprehensive literature review was done
      with respect to the major forms of syndromic craniosynostosis and additional less
      common FGFR-related forms of syndromic craniosynostosis. Additionally,
      information and data gathered from studies performed in our own investigative lab
      (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was
      also performed with regard to the genetic workup and diagnosis of patients with
      craniosynostosis. RESULTS: Patients with Apert syndrome (craniosynostosis
      syndrome due to mutations in FGFR2) are most severely affected in terms of
      intellectual disability, developmental delay, central nervous system anomalies,
      and limb anomalies. All patients with FGFR-related syndromic craniosynostosis
      have some degree of hearing loss that requires thorough initial evaluations and
      subsequent follow-up. CONCLUSIONS: Patients with syndromic craniosynostosis
      require management and treatment of issues involving multiple organ systems which
      span beyond craniosynostosis. Thus, effective care of these patients requires a
      multidisciplinary approach.

PMID- 22872263
TI  - High-resolution imaging of craniofacial sutures: new tools for understanding the
      origins of craniosynostoses.
AB  - AIM AND SCOPE: The developmental genetics and the biomechanics of sutures are
      well-studied topics, while their microanatomy is still imperfectly known. Here,
      we aim to investigate the structure of skull vault sutures using a high
      resolution imaging device. MATERIAL AND METHODS: We used synchrotron X-ray
      microtomography in order to obtain high-resolution images of skull vault sutures
      from an extant mammal (the mouse Mus musculus) and from an extinct fish (the
      placoderm Compagopiscis croucheri). We used segmentation and 3D reconstruction
      softwares in order to reveal the microanatomy of sutures in these species.
      RESULTS: The high-resolution images allowed us to study the distribution of
      osteocytes, the organisation of vascular canals, the shapes of the suture
      borders, the insertion of Sharpey's fibres, the bone growth lines and the
      structure of the soft tissues surrounding the sutures. CONCLUSION: Synchrotron
      imaging provides new perspectives for the study of the normal microanatomy of
      sutures. The submicronic resolution of the synchrotron scans gives access to the
      3D organisation of structures that were previously only known in 2D, even in
      normal sutures. The description of anatomical entities such as vascular canals
      and Sharpey's fibres in abnormally fused sutures would be of interest in the
      understanding of craniosynostoses.

PMID- 22872264
TI  - The role of vertebrate models in understanding craniosynostosis.
AB  - BACKGROUND: Craniosynostosis (CS), the premature fusion of cranial sutures, is a
      relatively common pediatric anomaly, occurring in isolation or as part of a
      syndrome. A growing number of genes with pathologic mutations have been
      identified for syndromic and nonsyndromic CS. The study of human sutural material
      obtained post-operatively is not sufficient to understand the etiology of CS, for
      which animal models are indispensable. DISCUSSION: The similarity of the human
      and murine calvarial structure, our knowledge of mouse genetics and biology, and
      ability to manipulate the mouse genome make the mouse the most valuable model
      organism for CS research. A variety of mouse mutants are available that model
      specific human CS mutations or have CS phenotypes. These allow characterization
      of the biochemical and morphological events, often embryonic, which precede
      suture fusion. Other vertebrate organisms have less functional genetic utility
      than mice, but the rat, rabbit, chick, zebrafish, and frog provide alternative
      systems in which to validate or contrast molecular functions relevant to CS.

PMID- 22872265
TI  - Phenotype profile of a genetic mouse model for Muenke syndrome.
AB  - PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15
      years ago, represents the single most common craniosynostosis mutation. Muenke
      syndrome is characterized by coronal suture synostosis, midface hypoplasia,
      subtle limb anomalies, and hearing loss. However, the spectrum of clinical
      presentation continues to expand. To better understand the pathophysiology of the
      Muenke syndrome, we present collective findings from several recent studies that
      have characterized a genetically equivalent mouse model for Muenke syndrome
      (FgfR3 (P244R)) and compare them with human phenotypes. CONCLUSIONS: FgfR3
      (P244R) mutant mice show premature fusion of facial sutures, premaxillary and/or
      zygomatic sutures, but rarely the coronal suture. The mice also lack the typical
      limb phenotype. On the other hand, the mutant mice display maxillary retrusion in
      association with a shortening of the anterior cranial base and a premature
      closure of intersphenoidal and spheno-occipital synchondroses, resembling human
      midface hypoplasia. In addition, sensorineural hearing loss is detected in all
      FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients. It is
      caused by a defect in the mechanism of cell fate determination in the organ of
      Corti. The mice also express phenotypes that have not been previously described
      in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone,
      and defective temporomandibular joint structure. Therefore, the FgfR3 (P244R)
      mouse provides an excellent opportunity to study disease mechanisms of some
      classical phenotypes of Muenke syndrome and to test novel therapeutic strategies.
      The mouse model can also be further explored to discover previously unreported
      yet potentially significant phenotypes of Muenke syndrome.

PMID- 22872266
TI  - The Fgfr2 W290R mouse model of Crouzon syndrome.
AB  - PURPOSE: This study aimed to review and discuss the utility of the Fgfr2 (W290R)
      mouse mutant as a model of human Crouzon syndrome. METHODS: A review of current
      and past scientific literature on Fibroblast Growth Factor Receptor-2 (FGFR2)
      protein domain structure, FGFR mutations associated with human Crouzon syndrome,
      and phenotypic and molecular changes combined with recent observations and
      experimental data of the Fgfr2 (W290R) mouse mutant was conducted. A comparison
      of the Fgfr2 (W290R) mouse mutant with another mouse model of Crouzon syndrome,
      Fgfr2 (C342R) mouse mutant, was also performed. Finally, possible future research
      directions using the Fgfr2 (W290R) mutant mice were discussed. RESULTS: The Fgfr2
      (W290R) heterozygous mouse exhibits defects characteristic of human Crouzon
      syndrome. At the molecular level, the defects observed in the mouse mutant are
      due to the dysregulation of signaling of both the IIIb and IIIc isoforms of
      Fgfr2. The involvement of the IIIb isoform of FGFR2 in the etiopathology of
      Crouzon syndrome is a novel finding in the craniosynostosis literature field.
      Dysregulated signaling of both IIIb and IIIc isoforms causes a broad spectrum of
      changes that explain some of the defects observed clinically in humans. Several
      of the defects observed in the Fgfr2 (W290R) homozygous mouse mutant are
      attributable to a loss-of-function mechanism in contrast to the frequently
      reported gain-of-function receptor function associated with mutated FGF receptors
      in craniosynostosis. CONCLUSIONS: The Fgfr2 ( W290R ) mouse model can be used as
      a model system to further investigate the cellular, molecular, and biochemical
      mechanisms of Crouzon syndrome.

PMID- 22872267
TI  - Mouse models of Apert syndrome.
AB  - INTRODUCTION: Apert syndrome is one of the more clinically distinct
      craniosynostosis syndromes in man. It is caused by gain-of-function mutations in
      FGFR2, over 98% of which are the two amino acid substitution mutations S252W and
      P253R. FGFR2 is widely expressed throughout development, so that many tissues are
      adversely affected in Apert syndrome, particularly the calvarial bones, which
      begin to fuse during embryonic development, and the brain. DISCUSSION: Mouse
      models of both of these two causative mutations and a third rare splice mutation
      have been created and display many of the phenotypes typical of Apert syndrome.
      The molecular and cellular mechanisms underlying Apert phenotypes have begun to
      be elucidated, and proof-of-principle treatment of these phenotypes by chemical
      inhibitor and gene-based therapies has been demonstrated.

PMID- 22872268
TI  - Complex craniosynostoses: a review of the prominent clinical features and the
      related management strategies.
AB  - The protocols for clinical evaluation and management of children with complex
      craniosynostoses are significantly different from those used in single suture
      forms. The time at which the various anatomical and functional anomalies observed
      in the affected subjects become clinically relevant varies from patient to
      patient, consequently requiring a tailored approach. The clinical course is
      variable and influenced by multiple factors, acting at different steps of the
      children growth. Intracranial hypertension is a major concern already in the
      first months of life; active cerebrospinal fluid (CSF) dynamics disorders, venous
      hypertension, and progressive craniocerebral disproportion are considered the
      main pathogenetic factors. Cranial vault and skull base sutures synostoses
      account for the frequently observed increased venous pressure. Skull base
      abnormalities lead to upper airways obstruction, which, on one side, might create
      significant upper airways obstructive problems and, on the other, contribute to
      the increase in the intracranial pressure. Secondary Chiari malformation is
      common and considered as a progressive disorder, mainly due to progressive
      craniocerebral disproportion, venous hypertension, and CSF dynamics disorders.
      Optic nerve and orbit-related eye-globe diseases are also a major concern.
      Papilledema is mostly related to increased intracranial pressure. The skull base
      synostotic process is the base of significant abnormalities of the orbital space,
      ending in the common feature of significant proptosis with the consequent risk of
      corneal ulcers. Aims of this paper are to analyze the physiopathogenetic
      mechanisms at the base of the clinical manifestations presented by children with
      complex craniosynostoses, and the therapeutic options currently available.

PMID- 22872269
TI  - The growth of the foramen magnum in Crouzon syndrome.
AB  - BACKGROUND: Though the craniovertebral junction is often abnormal in children
      with Crouzon's syndrome, no study had measured accurately the size of their
      foramen magnum (FM). PATIENTS AND METHODS: We compared the FM size (area,
      diameters) on computed tomography examination in 21 children with a genetically
      confirmed Crouzon's syndrome prior to any surgery and in 23 control children
      without craniofacial abnormalities. We extrapolated the growth pattern in both
      groups. RESULTS: We found a statistically significant smaller FM area (p=0.0228),
      FM sagittal diameter (p=0.0287), and FM sagittal posterior diameter (p=0.0023) in
      children with Crouzon's syndrome. No differences were detected with regard to the
      transversal diameter. Hydrocephalus in children with Crouzon's syndrome was
      associated with a small FM area (p=0.05), small sagittal diameter (p=0.023),
      small sagittal posterior diameter (p=0.0173), and reduced transversal diameter
      (p=0.03985). No association of the aforementioned findings was found with the
      position of the cerebellar tonsils or the lambdoid suture functional state (open
      or fused). Comparable results were observed among the two genetic forms (exon 8
      or 10 mutations). Concerning the growth pattern, a first phase of rapid increase
      and a second phase of slow increase could be recognized in all the measurements
      in both populations, though with some significant differences. DISCUSSION AND
      CONCLUSIONS: The growth of FM follows a biphasic pattern in both Crouzon's and
      control children. The sagittal diameter and the global size of the FM are mostly
      affected in children with Crouzon's syndrome. The small FM, especially its
      posterior part, is likely to play a key role in the physiopathology of
      hydrocephalus.

PMID- 22872270
TI  - Posterior cranial vault expansion in the treatment of craniosynostosis.
      Comparison of current techniques.
AB  - INTRODUCTION: Surgical procedures which aim at expanding the posterior cranial
      vault have come to play an increasingly important role in the treatment of
      syndromic craniosynostosis. The posterior cranial vault may be expanded by formal
      cranioplasty or by less invasive methods based on gradual posterior cranial vault
      expansion or distraction. These procedures share the common goals to prevent
      intracranial hypertension and progression toward turricephaly by effectively
      increasing the intracranial volume. They also reduce any local brain compression
      within the posterior cranial fossa. PATIENTS AND METHODS: This review describes
      the various techniques available for less invasive and gradual posterior cranial
      vault expansion and their rationale based on our experience on the last 40 cases.
      Volumetric data for three different surgical techniques have been compared (two
      cases of posterior cranial vault expansion by free-floating parieto-occipital
      bone flap, two with springs, and two with internal distractors). The volumetric
      analysis showed an expansion of 13 and 24 % for the free posterior flap, 18 and
      25 % for the translambdoid springs, and 22 and 29 % for the distractors.
      DISCUSSION: Although these figures are not strictly comparable, our data suggest
      that these three techniques offer a potential for a significant increase in skull
      volume. The indications for such procedures must, however, be tailored according
      to the age and condition of the single patient.

PMID- 22872271
TI  - Spring-assisted posterior skull expansion without osteotomies.
AB  - INTRODUCTION: A posterior flatness of the skull vault can be observed in infants
      with brachycephaly. Such posterior deformation favours the development of
      turricephaly which is difficult to correct. To reduce the risk of such
      deformation, an early posterior skull remodelling has been suggested.
      Translambdoid springs can be used to allow for a distraction through the patent
      lambdoid sutures and obtain a progressive increase of the posterior skull volume.
      SURGICAL TECHNIQUE: The procedure consists in a posterior scalp elevation, the
      patient being on a prone position. Springs made of stainless steel wire (1.5 mm
      in diameter) are bent in a U-type fashion, and strategically positioned across
      both lambdoid sutures. No drilling is usually necessary, as the lambdoid suture
      can be gently forced with a subperiosteal elevator in its middle and an
      indentation can be created with a bony rongeur on each side of the open suture to
      allow for a self-retention of bayonet-shaped extremity of the spring. Careful
      attention is addressed to the favoured prone position during the post-operative
      period. After a delay of 3-6 months, the springs can be removed during a second
      uneventful procedure, with limited incisions, usually as a preliminary step of
      the subsequent frontal remodelling. CONCLUSION: The concept of spring-assisted
      expansion across patent sutures under 6 months of age was confirmed in our
      experience (19 cases). Insertion of the springs allowed for immediate distraction
      across the suture. A posterior remodelling of the skull could be achieved with
      minimal morbidity allowing to delay safely a radical anterior surgery.

PMID- 22872272
TI  - Posterior cranial vault expansion using distraction osteogenesis.
AB  - PURPOSE: Posterior vault expansion using distraction osteogenesis has become a
      vital instrument in our institution, particularly as a first-line treatment in
      syndromic craniosynostosis. In this review, we highlight the several advantages,
      diverse utility, and technicalities of the operative procedure. METHODS: A review
      of the literature and explanation of the technical details of the procedures were
      described in this manuscript. RESULTS/CONCLUSION: Posterior cranial vault
      distraction offers several benefits over traditional expansion procedures.

PMID- 22872273
TI  - Faciocraniosynostosis: monobloc frontofacial osteotomy replacing the two-stage
      strategy?
AB  - BACKGROUND: Frontofacial monobloc advancement (FFMBA) is a powerful but high-risk
      procedure to correct both exorbitism and impaired airways of
      faciocraniosynostosis. PATIENTS AND METHODS: One hundred and five children with
      faciocraniosynostosis (mean 4.9 years, 7 months-14 years) were evaluated
      prospectively after FFMBA and quadruple internal distraction. The advancement was
      started at day 5 (0.5 mm/day). Mean follow-up was 61 months (maximum 10.5 years).
      Relapse was evaluated by the comparison between the evaluation at the time of
      removal of distractors and 6 months later. RESULTS: Seventy-six patients (72%)
      completed their distraction uneventfully in the initial period. COMPLICATIONS: -
      One death at D1 from acute tonsillar herniation before beginning of distraction. 
      Cerebrospinal fluid leaks managed conservatively (11 patients) and with
      transient lumbar drainage (eight patients). - Revision surgery
      (dysfunction/infection) of distraction devices (nine patients, subsequently four
      completed the distraction). Ninety-nine out of 104 patients finally completed
      their distraction, resulting in exorbitism correction. Respiratory impairment,
      when present, was corrected and class I occlusal relationship was obtained in 77%
      of the cases. Reossification was limited at the orbital level but relapse could
      be prevented by a retention phase of 6 months. Pfeiffer syndrome, previous
      surgeries, and surgery before 18 months of age were risk factors. CONCLUSIONS:
      Internal distraction allows early correction of respiratory impairment and
      exorbitism of faciocraniosynostosis. In order to limit the risks, we advise: -
      Preliminary craniovertebral junction decompression if needed - Four devices to
      customize the distraction - Double pericranial flap to seal the anterior cranial
      fossa - Systematical external transient drainage if CSF leak - Slow rate of
      distraction (0.5 mm/day) - Long consolidation phase (6 months).

PMID- 22872274
TI  - External craniofacial osteodistraction in complex craniosynostoses.
AB  - PURPOSE: The use of distraction osteogenesis is the first option in the treatment
      of craniofacial hypoplasia. Both internal craniofacial distractor devices (ICDD)
      and external craniofacial distractor devices (ECDD) can improve visual and
      respiratory functions in patients with craniofacial synostosis significantly.
      They also improve the cosmetic outcome. DISCUSSION: We reviewed the pertinent
      literature concerning the use of ECDD in complex craniostenosis. Surgical data as
      well as quality of life notes were analyzed and compared with those reported for
      ICDD. CONCLUSION: The advantage of ECDD compared with ICDD is the easier
      application and postoperative management as compared with ICDD, with comparable
      results for extent and quality of distraction osteogenesis. The disadvantage is
      the quality of life which most authors report is worse if compared to ICDD during
      the distraction osteogenesis period.

PMID- 22872275
TI  - Complications of frontofacial advancement.
AB  - PURPOSE: The purpose of this study was to document the early and late
      complications associated with frontofacial distraction. METHOD: A systematic
      review of the literature on complications in craniofacial surgery and a review of
      records of patients undergoing frontofacial distraction at Great Ormond Street
      Hospital for Children over a 10-year period were conducted. RESULTS:
      Complications arising from frontofacial advancement are common. Mortality rates
      varied between 0 and 4.5 %. There has been a general decline in reported
      mortality rates with time, and the most recent series report mortalities of less
      than 1 %. The incidence of significant blood loss (greater than one blood volume)
      in patients undergoing monobloc osteotomy varied between 5.3 and 9.1 %. CSF leaks
      following monobloc distraction are common (incidence, 2-20 %). Most of these
      leaks settle spontaneously. The incidence of frontal bone flap necrosis requiring
      debridement and a subsequent cranioplasty varied between 3 and 20 %. CONCLUSIONS:
      The functional and aesthetic benefits of frontofacial distraction are well
      documented, but these advantages are associated with a significant complication
      rate. The potential benefits of frontofacial distraction need to be carefully
      weighed against the potential complications when deciding to recommend surgery.

PMID- 22872278
TI  - Hume-Rothery stabilization mechanism and e/a determination for RT- and MI-type
      1/1-1/1-1/1 approximants studied by FLAPW-Fourier analyses.
AB  - Full-potential linearized augmented plane wave (FLAPW) electronic band
      calculations were performed for two RT- (rhombic triacontahedron) and five MI-
      (Mackay icosahedron) type 1/1-1/1-1/1 approximants plus several complex metallic
      compounds in Al-TM (TM = transition metal element) binary alloy systems in order
      to elucidate the origin of a pseudogap from the viewpoint of Fermi surface
      Brillouin zone (FsBz) interactions. The square of the Fermi diameter (2k(F))(2)
      and square of the critical reciprocal lattice vector |G|(2) or the critical set
      of lattice planes, with which electrons at the Fermi level E(F) are interfering,
      can be extracted from the FLAPW-Fourier method. We revealed that a pseudogap in
      both RT- and MI-type 1/1-1/1-1/1 approximants universally originates from
      interference phenomenon satisfying the matching condition (2k(F))(2) = |G|(2)
      equal to 50 in units of (2pi/a)(2), where a is the lattice constant. The multi
      zone effect involving not only |G|(2) = 50 but also its neighboring ones is also
      claimed to be responsible for constituting a pseudogap across E(F). The value of
      e/a for Mn, Fe, Re and Ru elements in the periodic table is deduced to be
      positive in the neighborhood of unity. All 1/1-1/1-1/1 approximants, regardless
      of RT- or MI-type atomic cluster involved, are stabilized at around e/a= 2.7,
      while their counterpart quasicrystals are at around e/a= 2.2. A new Hume-Rothery
      electron concentration rule linking the number of atoms per unit cell, e/uc, with
      a critical|G|(2) holds well for all complex intermetallic compounds characterized
      by a pseudogap at E(F).

PMID- 22872276
TI  - A review of reconstructive materials for use in craniofacial surgery bone
      fixation materials, bone substitutes, and distractors.
AB  - Over the last 40 years, craniofacial surgery, in general, and surgery for
      craniosynostosis, in particular, has witnessed the introduction of a number of
      new materials for use in operations involving the cranial vault. Some of these
      materials have proven quite useful over time, while others have failed to meet
      their stated objectives. In this review, the more popular implant materials are
      analyzed, and their relative merits and drawbacks are discussed. Craniofacial
      surgery in the pediatric population has its own unique limitations, quite
      different from the adult population and those issues are reviewed as well.

PMID- 22872279
TI  - Ultra-structural observation of human enamel and dentin by ultra-high-voltage
      electron tomography and the focus ion beam technique.
AB  - Human enamel and dentin are hard and brittle mineralized tissues. It is difficult
      to prepare thin specimens (under 200 nm) of these tissues for transmission
      electron microscope observation without demineralizing them. We present a novel
      method of creating three-dimensional ultra-structural images of human enamel and
      dentin, using the focus ion beam (FIB) method and ultra-high-voltage electron
      microscope tomography. Thin specimens (less than 2 MUm) of enamel and dentin were
      prepared using the FIB method. This method is appropriate for nano-fabrication of
      thin specimens for brittle materials such as enamel and dentin. It allows
      penetration of an ultra-high-voltage electron beam of a 3000 kV maximal
      acceleration voltage into a specimen, enabling projections of the specimen to be
      taken. It facilitates tomography of the enamel rods, sheaths, dentinal tubules
      and collagen fibrils with a high resolution of 2 nm. The component percentages in
      ultra-structures of dentin can be expressed numerically by using three
      dimensional reconstruction images of tomograms. The matrix of peritubular dentin
      differed from that of intertubular dentin by having relatively fewer collagen
      fibrils. The major advantage of this method is its ability to visualize ultra
      structural tomograms of highly calcified specimens without demineralization.

PMID- 22872280
TI  - From the physics of secondary electron emission to image contrasts in scanning
      electron microscopy.
AB  - Image formation in scanning electron microscopy (SEM) is a combination of
      physical processes, electron emissions from the sample, and of a technical
      process related to the detection of a fraction of these electrons. For the
      present survey of image contrasts in SEM, simplified considerations in the
      physics of the secondary electron emission yield, delta, are combined with the
      effects of a partial collection of the emitted secondary electrons. Although some
      consideration is initially given to the architecture of modern SEM, the main
      attention is devoted to the material contrasts with the respective roles of the
      sub-surface and surface compositions of the sample, as well as with the roles of
      the field effects in the vacuum gap. The recent trends of energy filtering in
      normal SEM and the reduction of the incident energy to a few electron volts in
      very low-energy electron microscopy are also considered. For an understanding by
      the SEM community, the mathematical expressions are explained with simple
      physical arguments.

PMID- 22872281
TI  - In situ crystallization of barium zinc silicate in glass-ceramics studied by hot
      stage scanning electron microscopy.
AB  - Glasses with the mol% composition 30ZnO, 10Na(2)O, 10BaO and 50SiO(2) were
      annealed at 700 degrees C and 760 degrees C ex situ as well as in situ using a
      hot stage scanning electron microscope (SEM). The formed crystal phase
      (BaZn(2)Si(2)O(7)) was proved ex situ by X-ray diffraction. Annealing the glass
      samples in the SEM resulted in a strong surface crystallization, which was
      monitored for 1 h and 21 min and 2 h and 2 min at the temperatures 700 degrees C
      and 760 degrees C, respectively. The crystal growth velocities for these two
      temperatures were determined from a series of micrographs. It is experimentally
      shown that during the course of the crystallization in this non-isochemical
      system, the residual glassy phase changes its composition, and hence, the crystal
      growth velocity depends on time. Furthermore, it is shown that the electron beam
      irradiation directly affects the nucleation and crystal growth velocities.

PMID- 22872282
TI  - Use of the unroofing technique for atomic force microscopic imaging of the intra
      cellular cytoskeleton under aqueous conditions.
AB  - Atomic force microscopy (AFM) combined with unroofing techniques enabled clear
      imaging of the intracellular cytoskeleton and the cytoplasmic surface of the cell
      membrane under aqueous condition. Many actin filaments were found to form a
      complex meshwork on the cytoplasmic surface of the membrane, as observed in
      freeze-etching electron microscopy. Characteristic periodic striations of about 5
      nm formed by the assembly of G-actin were detected along actin filaments at
      higher magnification. Actin filaments aggregated and dispersed at several points,
      thereby dividing the cytoplasmic surface of the membrane into several large
      domains. Microtubules were also easily detected and were often tethered to the
      membrane surface by fine filaments. Furthermore, clathrin coats on the membrane
      were clearly visualized for the first time in water by AFM. Although the
      resolution of these images is lower than electron micrographs of freeze-etched
      samples processed similarly, the measurement capabilities of the AFM in a more
      biologically relevant conditions demonstrate that it is an important tool for
      imaging intracellular structures and cell surfaces in the native, aqueous state.

PMID- 22872283
TI  - Excessive daytime sleepiness in late pregnancy may not always be normal: results
      from a cross-sectional study.
AB  - PURPOSE: Many changes that normally occur during pregnancy disrupt sleep and may
      lead to excessive daytime sleepiness (EDS). However, given that pregnancy may
      also predispose to the development of sleep-disordered breathing (SDB), we sought
      to investigate whether EDS may be associated with snoring, gasping, or apneas,
      further suggesting SDB. METHODS: A cross-sectional survey of women in the
      immediate postpartum period was conducted. Participants answered questions from
      the multivariable apnea prediction index regarding snoring, gasping, and
      witnessed apneas in the last 3 months of pregnancy. Participants were also asked
      to answer Epworth Sleepiness Scale (ESS) questions, and a score 0-24 was
      calculated (>10 considered abnormal). Medical history and medication use were
      obtained both by history and review of the medical record. RESULTS: Out of 1,000
      women recruited, 990 women answered the ESS questionnaire completely. Mean
      prepregnancy body mass index (BMI) was 26.1 +/- 6.2 with 21.7 % of the sample
      having a prepregnancy BMI >=30. Mean ESS score was 7.1 +/- 3.9, and 1.7 % of the
      total sample scored 16 or greater. ESS increased significantly with age, BMI, and
      neck circumference. All three symptoms of SDB were associated with higher mean
      ESS scores. In a multiple linear regression analysis, loud snoring, gasping, and
      apneas were statistically significant independent predictors of mean ESS score.
      CONCLUSIONS: EDS measured by ESS is a common finding in pregnancy. Snoring,
      gasping, and apneas appear to be independent predictors of mean ESS scores.

PMID- 22872285
TI  - Optically active, lyotropic liquid crystalline poly(diphenylacetylene)
      derivative: hierarchical chiral ordering from isotropic solution to anisotropic
      solid films.
AB  - The side chain chirality of a poly(diphenylacetylene) derivative was transferred
      and amplified spontaneously from solution to a bulk film due to lyotropic liquid
      crystallinity.

PMID- 22872284
TI  - Supine fluid redistribution: should we consider this as an important risk factor
      for obstructive sleep apnea?
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) is a common medical disorder
      affecting at least 2 % of women and 4 % of men living in Western societies.
      Obesity, older age, male gender, alcohol and sedative use, smoking, craniofacial
      parameters, and volume overload are some of the risk factors for this disorder.
      DISCUSSION: OSA is a known risk factor complicating the course of arterial
      hypertension, heart failure, and chronic kidney disease. It is important to note
      that all of the aforementioned comorbid disorders are associated with volume
      overload. This explains why patients with OSA and comorbid disorders associated
      with fluid overload can benefit from treatment with diuretics and drugs
      modulating the renin-angiotensin-aldosterone system. Additionally, patients with
      heart failure and high sodium intake are at increased risk for OSA, further
      supporting the complex interrelationship. CONCLUSIONS: Hemodialysis and renal
      transplantation can markedly improve the severity of OSA in patients with
      concomitant kidney disease. Finally, there is a potential of a vicious cycle
      between OSA and fluid overload disorders, whereby OSA can contribute to the
      pathogenesis of arterial hypertension, heart failure, and chronic kidney disease,
      which in turn will significantly contribute to the course OSA.

PMID- 22872286
TI  - Iron deficiency after arrival is associated with general cognitive and behavioral
      impairment in post-institutionalized children adopted from Eastern Europe.
AB  - To investigate the role of iron deficiency in general cognitive and behavioral
      development in post-institutionalized (PI) children during the early post
      adoption period. PI children (N = 57) adopted from Eastern Europe or Central Asia
      (9-46 months of age) were seen at baseline around 1 month after arrival into the
      US and at follow-up 6 months later. Measures included anthropometry, iron status,
      the Toddler Behavior Assessment Questionnaire-R (TBAQ-R), the Mullen Scales of
      Early Learning, and examiner-rated behaviors during testing. 26 % were iron
      deficient at baseline; 18 % were iron deficient at follow-up. There was a trend
      for those with iron deficiency at baseline to be more fearful on the TBAQ-R.
      Those with iron deficiency at follow-up displayed more hyperactivity on both the
      TBAQ-R and the examiner-rated behaviors. Those with iron deficiency at follow-up
      were more likely to score below average on the Mullen Early Learning Composite
      (iron deficient: 80 %; good iron status: 32 %). The association between iron
      status at follow-up and the Mullen Early Learning Composite was mediated by
      inattention and hyperactivity behaviors during testing. Iron deficiency is
      associated with neurobehavioral alterations months after arrival, mediated by the
      effect on attention and activity levels. Iron status needs to be monitored at
      least through the first half-year post-adoption, particularly in children
      exhibiting rapid catch-up growth. Additionally, developmental evaluation is
      recommended in those with iron deficiency, even in children with good iron status
      at arrival.

PMID- 22872287
TI  - Association of postalimentary lipemia with atherosclerotic manifestations.
AB  - We identified different lipemic and metabolic responses after the ingestion of a
      standardized meal by healthy adults and related them to atherosclerotic markers.
      Samples from 60 normolipidemic adults were collected before and after a liquid
      meal (40 g fat/m2 body surface) at 0, 2, 4, 6, and 8 h for measurements of
      lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein
      (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic
      activities, and apolipoprotein E polymorphism. Mean carotid intima-media
      thickness (cIMT) was determined by Doppler ultrasound. The volunteers were
      classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders
      to the test meal. Late responders showed lower HDL cholesterol concentration at
      fasting and in the TAG peak, lower insulin and higher FFA concentrations compared
      to early responders. Multivariate regression analyses showed that mean cIMT was
      associated with gender (male) and age in early responders and by cholesterol
      levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein
      lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP
      (negative) and FFA (positive). This study is the first to identify a
      postalimentary insulin resistance state, combined with a reduced CETP response
      exclusively among late responders, and the identification of the regulators of
      postalimentary atherogenicity. Further research is required to determine the
      metabolic mechanisms described in the different postalimentary phenotypes
      observed in this study, as well as in different pathological states, as currently
      investigated in our laboratory.

PMID- 22872288
TI  - RNAi-mediated knockdown of pituitary tumor- transforming gene-1 (PTTG1)
      suppresses the proliferation and invasive potential of PC3 human prostate cancer
      cells.
AB  - Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes
      tumorigenesis and metastasis in numerous cell types and is overexpressed in a
      variety of human tumors. We have demonstrated that PTTG1 expression was up
      regulated in both human prostate cancer specimens and prostate cancer cell lines.
      For a more direct assessment of the function of PTTG1 in prostate tumorigenesis,
      RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3
      human prostate tumor cells. After three weeks of selection, colonies stably
      transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty
      vector (the control PC3 cell line) were selected and expanded to investigate the
      role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate
      was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth
      as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar
      colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3
      cell colonies than control colonies after three weeks of growth. In addition,
      PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence
      activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited
      significantly reduced migration through Matrigel in a transwell assay of invasive
      potential, and down-regulation of PTTG1 could lead to increased sensitivity of
      these prostate cancer cells to a commonly used anticancer drug, taxol. Thus,
      PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be
      a promising new target for prostate cancer therapy.

PMID- 22872290
TI  - Prognostic value of renin-angiotensin system blockade in non-muscle-invasive
      bladder cancer.
AB  - BACKGROUND: To determine whether the administration of renin-angiotensin system
      (RAS) inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) or
      angiotensin II receptor blockers (ARBs), affect disease outcome in non-muscle
      invasive bladder cancer (NMIBC). METHODS: A total of 330 patients with initially
      diagnosed NMIBC were identified. We retrospectively investigated the clinical
      outcomes after transurethral resection of bladder tumor (TUR-BT) in patients who
      did or did not receive RAS inhibitors. The median follow-up period was 4.1 years.
      RESULTS: A total of 128 patients (38.8 %) experienced subsequent tumor
      recurrence, and stage progression was observed in 17 patients (5.2 %) during
      follow-up. Fifty-one patients (15.5 %) had received ACEI or ARB administration at
      transurethral resection. Multivariate analysis demonstrated that tumor
      multiplicity, absence of bacillus Calmette-Guerin instillation, and no
      administration of ACEI or ARB (P = 0.010, hazard ratio 2.26) were independent
      risk factors for subsequent tumor recurrence. The 5-year recurrence-free survival
      rate was 78.4 % in patients administered ACEIs or ARBs, and 53.3 % in their
      counterparts (P = 0.011). CONCLUSIONS: The absence of RAS inhibitor
      administration was an independent risk factor for subsequent tumor recurrence in
      patients with initially diagnosed NMIBC. Our data support further investigation
      of the role of RAS inhibitors as a potential therapy to decrease tumor recurrence
      in NMIBC.

PMID- 22872291
TI  - Evaluation of appropriate short-term mammographic surveillance in patients who
      undergo breast-conserving Surgery (BCS).
AB  - BACKGROUND: Mammography is an important surveillance tool for detecting
      ipsilateral breast tumor recurrence (IBTR) after BCS. Although IBTR is rare in
      the first 2 years, various organizations have established protocols for
      postoperative mammographic surveillance. Currently there is no consensus on the
      optimal interval for imaging evaluation of patients following BCS. METHODS: We
      conducted a retrospective review of patients who underwent BCS at Aultman
      Hospital between 1/06 and 12/08. To be included in the study, patients had to be
      diagnosed with invasive primary breast carcinoma or ductal carcinoma in situ
      (DCIS), treated with BCS (with or without postoperative breast radiation), and
      have had at least one postoperative surveillance mammogram at our Breast Care
      Center. Our mammographic surveillance protocol for patients undergoing BCS
      consists of ipsilateral mammograms (affected side) around 6 and 18 months and
      bilateral mammograms around 12 and 24 months. All mammograms that were Breast
      Imaging-Reporting and Data System (BIRADS) 0 or 4 were reviewed by a single
      radiologist (T.B.P.). RESULTS: A total of 375 patients constituted the core group
      for this study. Each interval mammographic screening (6- and 18-month mammograms)
      resulted in additional imaging in 3-4 % of patients. There was a very low yield
      for identifying IBTR: 1/266 (0.4 %) for the 5-10-month postoperative mammogram
      and 1/286 (0.3 %) for the 16-21-month postoperative mammogram. CONCLUSIONS: Based
      on our data and the low expected yield of IBTR in the first 2 years, annual
      mammographic surveillance appears adequate following BCS and interval ipsilateral
      mammograms at 6 and 18 months do not provide additional clinical benefit.

PMID- 22872292
TI  - Outcome analyses of unusual site neck recurrence in oral cavity cancer.
AB  - AIM: To understand the frequency, clinical significance, and benefits of salvage
      therapy in oral cavity squamous cell carcinoma (OSCC) patients with regional
      nodal recurrence at unusual sites (prelaryngeal area, parotid area, and
      retropharyngeal area). METHODS: We examined 178 patients with neck recurrence at
      levels I-V (usual group) and 26 patients outside levels I-V (unusual group). The
      5-year survival rates served as the main outcome measure. RESULTS: Of the 26
      unusual group patients, the neck recurrence sites were as follows: 5 at the
      prelaryngeal area, 13 at the parotid area, and 8 at the retropharyngeal area.
      Multivariate analyses demonstrated that poor differentiation, pN2, extracapsular
      spread (ECS), tumor depth>=10 mm, relapse time<=10 months, local recurrence, neck
      recurrence at unusual sites, and distant metastases were independent prognostic
      factors for 5-year disease-specific survival (DSS), whereas pN2, ECS, tumor
      depth>=10 mm, relapse time<=10 months, neck recurrence at unusual sites, and
      distant metastases were independent prognostic factors for 5-year overall
      survival (OS). The 6-month and 18-month survival rates after the N-relapse date
      for the salvaged-usual group, the salvaged-unusual group, and the nonsalvaged
      patients were 73%/46%, 40%/0%, and 10%/0% (P<0.0001), respectively [DSS: salvaged
      unusual group (hazard ratio/95 % confidence interval), 2.060/1.058-4.008,
      P=0.033; salvaged-usual group, 6.420/4.340-9.496, P<0.001; OS: salvaged-unusual
      group, 2.100/1.080-4.081, P=0.029; salvaged-usual group, 6.514/4.418-9.606,
      P<0.001]. CONCLUSIONS: Our findings demonstrate that OSCC patients with regional
      nodal recurrence at unusual sites had poor outcomes.

PMID- 22872294
TI  - Chemical silicon surface modification and bioreceptor attachment to develop
      competitive integrated photonic biosensors.
AB  - Methodology for the functionalization of silicon-based materials employed for the
      development of photonic label-free nanobiosensors is reported. The studied
      functionalization based on organosilane chemistry allowed the direct attachment
      of biomolecules in a single step, maintaining their bioavailability. Using this
      immobilization approach in probe microarrays, successful specific detection of
      bacterial DNA is achieved, reaching hybridization sensitivities of 10 pM. The
      utility of the immobilization approach for the functionalization of label-free
      nanobiosensors based on photonic crystals and ring resonators was demonstrated
      using bovine serum albumin (BSA)/anti-BSA as a model system.

PMID- 22872295
TI  - Deceased donors and commercial transplantation.

PMID- 22872296
TI  - Aseptic osteonecrosis: a newly diagnosed complication in HIV-infected patients
      undergoing liver transplantation.

PMID- 22872297
TI  - A randomized, double-blind, placebo-controlled study of single dose rituximab as
      induction in renal transplantation:  a 3-year follow-up.

PMID- 22872298
TI  - A cascade reaction of azolopyrimidines. Synthesis of unusual indole and azaindole
      derivatives.
AB  - The reaction of bromo substituted pyrido[3',2':4,5]pyrrolo-[1,2-c]pyrimidine and
      pyrimido[1,6-a]indole methyl carboxylates with primary amines is described. The
      expected amide formation occurs but it is followed by an unexpected cascade
      process involving attack of the amine to the pyrimidine ring, opening of the
      pyrimidine ring, loss of the bromine substituent and competitive cyclizations to
      afford unusual imidazolidene substituted indoles and azaindoles.

PMID- 22872299
TI  - Instrumented measurement of balance and postural control in individuals with
      lower limb amputation:  a critical review.
AB  - Measurement of balance and postural performance that underpins activities of
      daily living is important in the rehabilitation of individuals with a lower limb
      amputation (LLA), and there are a number of methods and strategies available for
      this purpose. To provide an evidence-based choice of approach, this review aims
      to critically review the tasks and outcome measures utilized in studies
      investigating static and dynamic balance using instrumented measurement devices
      in individuals with a LLA. A systematic search was conducted on multiple
      databases using keyword or subject headings appropriate to the respective
      database. Articles investigating static or dynamic balance in adults with LLA by
      means of instrumented measures were considered for the review. A total of 21
      articles were included in the review. The static balance ability of individuals
      with an LLA has been investigated thoroughly, but their dynamic balance
      attributes remain relatively unexplored. Although the individual studies do
      provide valuable information on balance ability in the LLA, the heterogeneity in
      study designs and measures did not allow an overall analysis of the tasks and the
      outcome measures used. On the basis of these findings, this review provides an
      insight into the measurement of balance in amputees to inform novice researchers
      and clinicians working with individuals with an LLA.

PMID- 22872300
TI  - EuroQol 5D quality of life in Meniere's disorder can be explained with symptoms
      and disabilities.
AB  - The purpose of this study was to determine the factors explaining changes in the
      generic quality of life among patients with Meniere's disorder (MD) and to
      evaluate the EuroQol 5D (EQ-5D) quality-of-life measures. A questionnaire
      focusing on symptoms and disabilities caused by MD was collected from 726
      individuals. General health-related quality of life (EQ-5D) was evaluated using
      the time trade-off (TTO) and visual-analogue scale (VAS). Personal traits were
      measured with the sense of coherence. The TTO-VAS score difference was modeled
      with activity limitations, participation restrictions, attitudes, and symptoms.
      For TTO as the outcome measure, one symptom-based, three attitude-based, one
      activity limitation, and one participation restriction item explained 43% of the
      variability. For VAS, six attitude-based, one symptom-based, three activity
      limitations, and one participation restriction item explained 43% of the
      variability of the data. The correlation between TTO and VAS (r=0.515, P<0.001)
      explained only 27% of the variance. The difference between TTO and VAS was
      reflected in attitudes towards the illness. The model explained 10% of the
      variability in the VAS and TTO difference. There was a disease duration effect in
      the TTO-VAS difference. In conclusion, a symptom-based model combined with
      disabilities provided a good description of general quality of life in MD. The
      TTO-based and VAS-based evaluation explained somewhat different aspects of MD.
      The difference between TTO and VAS could be described as an attitude toward the
      ailment. Evaluation of disabilities and the difference in TTO and VAS can be used
      to guide the rehabilitation to promote attitude change.

PMID- 22872301
TI  - Effect of home exercise program performance in patients with osteoarthritis of
      the knee or the spine on the visual analog scale after discharge from physical
      therapy.
AB  - The aim of our study was to assess the effect of the frequency of home exercise
      program (HEP) performance on pain [10-point visual analog scale (VAS)] in
      patients with osteoarthritis of the spine or knee after more than 6 months
      discharge from physical therapy (PT). We performed a retrospective chart review
      of 48 adult patients with a clinical diagnosis of knee or spine osteoarthritis
      and had been discharged from PT of the spine or the knee for at least 6 months
      with provision of HEP from a physical therapist. Adult patients who were younger
      than 50 years of age, taking more than one medication to control pain,
      participating in worker's compensation, or had a history of drug abuse were
      excluded from the study. We recorded patient demographics, pain level (10-point
      VAS scale), and the number of days that a HEP was performed per week. The mean
      VAS score of patients who performed 0 days of HEP per week was 6.90. The mean VAS
      score of patients who performed HEP 1-3 times per week was 6.36. The mean VAS
      score of patients who performed HEP 4-7 times per week was 5.00. Single-factor
      analysis of variance analysis indicated a P-value of less than 0.01. Post-hoc
      comparison of the mean VAS using Fisher's least significant difference test
      showed a significant difference between the mean VAS score of 4-7 days per week
      of HEP versus 0 days per week (P<0.01) and 1-3 days per week (P<0.01) of HEP.
      There was no significant difference in the mean VAS score between 0 days of HEP
      and 1-3 days of HEP (P>0.05). Patients who performed 4-7 days per week of HEP had
      statistically significant lower mean VAS scores than patients who performed 0
      days per week of HEP and 1-3 days per week of HEP. Therefore, after 6 months of
      discharge from PT, patients should be encouraged to perform at least 4 days of
      HEP per week.

PMID- 22872302
TI  - Using the Hand Laterality Judgement Task to assess motor imagery: a study of
      practice effects in repeated measurements.
AB  - The aim of this study was to determine whether there is a practice effect on the
      Hand Laterality Judgement Task (HLJT). The HLJT task is a mental rotation task
      that can be used to assess motor imagery ability in stroke patients. Thirty-three
      healthy individuals performed the HLJT and two control tasks twice at a 3-week
      interval. Differences in the accuracy and the response times were analysed. The
      results for all three tasks showed a decrease in the response time between the
      first and the second assessments (8-20%), and, for the HLJT, also a small (3%)
      but relevant increase in accuracy. The most likely factor explaining this
      improvement is that of practice effects. This implies that an improvement in the
      HLJT scores found over time in clinical research may be partly because of a
      learning effect, which has to be taken into account when interpreting the
      results. It is likely that a practice effect occurs in repeated measurements of
      the HLJT.

PMID- 22872303
TI  - New diagnostic criteria and severity assessment of acute cholecystitis in revised
      Tokyo Guidelines.
AB  - BACKGROUND: The Tokyo Guidelines for the management of acute cholangitis and
      cholecystitis (TG07) were published in 2007 as the world's first guidelines for
      acute cholangitis and cholecystitis. The diagnostic criteria and severity
      assessment of acute cholecystitis have since been widely used all over the world.
      A validation study of TG07 has shown that the diagnostic criteria for acute
      cholecystitis are highly reliable but that the definition of definite diagnosis
      is ambiguous. In addition, considerable new evidence referring to acute
      cholecystitis as well as evaluations of TG07 have been published. Consequently,
      we organized the Tokyo Guidelines Revision Committee to evaluate TG07, recognize
      new evidence, and conduct a multi-center analysis to revise the guidelines
      (TG13). METHODS AND MATERIALS: We retrospectively analyzed 451 patients with
      acute cholecystitis from multiple tertiary care centers in Japan. All 451
      patients were first evaluated using the criteria in TG07. The "gold standard" for
      acute cholecystitis in this study was a diagnosis by pathology. The validity of
      TG07 diagnostic criteria was investigated by comparing clinical with pathological
      diagnosis. RESULTS: Of 451 patients evaluated, a total of 227 patients were given
      a diagnosis of acute cholecystitis by pathological examination (prevalence 50.3
      %). TG07 criteria provided a definite diagnosis of acute cholecystitis in 224
      patients. The sensitivity of TG07 diagnostic criteria for acute cholecystitis was
      92.1 %, and the specificity was 93.3 %. Based on the preliminary results, new
      diagnostic criteria for acute cholecystitis were proposed. Using the new
      criteria, the sensitivity of definite diagnosis was 91.2 %, and the specificity
      was 96.9 %. The accuracy rate was improved from 92.7 to 94.0 %. In regard to
      severity grading among 227 patients, 111 patients were classified as Mild (Grade
      I), 104 as Moderate (Grade II), and 12 as Severe (Grade III). CONCLUSION: The
      proposed new diagnostic criteria achieved better performance than the diagnostic
      criteria in TG07. Therefore, the proposed criteria have been adopted as new
      diagnostic criteria for acute cholecystitis and are referred to as the 2013 Tokyo
      Guidelines (TG13). Regarding severity assessment, no new evidence was found to
      suggest that the criteria in TG07 needed major adjustment. As a result, TG07
      severity assessment criteria have been adopted in TG13 with minor changes.

PMID- 22872304
TI  - Reappraise the effect of redo-Kasai for recurrent jaundice following Kasai
      operation for biliary atresia in the era of liver transplantation.
AB  - PURPOSE: This study was conducted to reappraise the efficacy of redo-Kasai (or
      revision) in the era of liver transplantation as a treatment option in those
      patients with recurrent jaundice after initially successful Kasai procedure.
      METHODS: We studied ten patients that received redo-Kasai, among a total of 102
      patients diagnosed with biliary atresia after receiving Kasai operation from 1986
      to 2011. RESULTS: Kasai operation was done at a median age of 55 days and redo
      Kasai at 150 days. The bilirubin levels returned to normal in six patients after
      the procedure. Four of six enjoyed jaundice-free survival with native liver till
      the time of last follow-up. Three patients died and three received liver
      transplantation (LT). Only one out of seven patients with three or more episodes
      of cholangitis survived with native liver, while all the three patients with 1 or
      0 episode survived with native liver. The difference was significant (P = 0.033).
      Re-do Kasai did not result in more blood loss or operative time during LT.
      CONCLUSION: Redo-Kasai is still valuable in the era of LT and the episodes of
      cholangitis are the decisive factors affecting the outcome of the procedure.

PMID- 22872305
TI  - Class III gynecomastia in pediatric age: a new modified surgical treatment.
AB  - BACKGROUND: Prepubertal gynecomastia is an extremely rare condition usually
      requiring surgical treatment, especially in case of class III gynecomastia. This
      study presents cases treated with a new surgical treatment. METHODS: From 2010 at
      our institution, gynecomastia is treated surgically using a modified technique of
      periareolar incision. Aesthetic results and possible complications of this
      technique are reported. RESULTS: Five patients were treated at the authors' unit
      for class III gynecomastia between January 2010 and December 2011. All patients
      were properly treated without the need of further surgery for skin resection. One
      patient developed seroma, treated with suction; one patient showed hematoma,
      treated with hot packs for 3 weeks. All patients and their parents were satisfied
      of the aesthetic results obtained. All patients resumed sport activities 4 weeks
      after surgery. It was not possible to observe intraoperative complications.
      CONCLUSION: The technique used meets safety and efficacy standards for the
      treatment of this type of pediatric gynecomastia. It also offers the best
      possible aesthetic results with minimum complications which can be treated
      without the need of further surgery.

PMID- 22872308
TI  - Head-to-head comparison between SRS, (18)F-FDG and (18)F-FDOPA PET/CT in a
      patient with recurrent SDHC-related jugular paraganglioma.

PMID- 22872307
TI  - Posterior parietooccipital hypometabolism may differentiate mild cognitive
      impairment from dementia in Parkinson's disease.
AB  - PURPOSE: Patients with Parkinson's disease (PD) may have normal cognition, mild
      cognitive impairment (MCI) or dementia. We investigated differences in cerebral
      metabolism associated with these three cognitive states and the relationship
      between metabolism and cognitive dysfunction. METHODS: FDG PET and a battery of
      neuropsychological tests were used to study PD patients with dementia (n = 19),
      MCI (n = 28) and normal cognition (n = 21), and control subjects (n = 20).
      Regional glucose metabolism in patients and controls was analysed using
      statistical parametric mapping (SPM8) corrected for age, motor severity and
      depression. Correlations between the mini-mental state examination score and Z
      score values of the different cognitive domains with respect to cerebral FDG
      uptake were assessed using SPM8. RESULTS: PD patients with MCI (PD-MCI patients)
      exhibited decreased FDG uptake in the frontal lobe, and to a lesser extent in
      parietal areas compared with cognitively normal patients. Patients with dementia
      showed reduced metabolism in the parietal, occipital and temporal areas and a
      less extensive reduction in the frontal lobe compared with PD-MCI patients, while
      widespread hypometabolism was seen in comparison with patients with normal
      cognition. PD-MCI patients exhibited reduced FDG uptake in the parietal and
      occipital lobes and in localized areas of the frontal and temporal lobes compared
      with controls, whereas patients with dementia showed a widespread reduction of
      cortical metabolism. Mini-mental state examination score correlated positively
      with metabolism in several lobes, executive function with metabolism in the
      parietooccipitotemporal junction and frontal lobe, memory with temporoparietal
      metabolism, visuospatial function with occipitoparietal and temporal metabolism,
      and language with frontal metabolism. CONCLUSION: PD patients with MCI exhibited
      hypometabolism in several cortical regions compared with controls, and in the
      frontal and parietal regions compared with cognitively normal patients.
      Hypometabolism was higher in patients with dementia than in those with MCI,
      mainly in the posterior cortical areas where it was correlated with visuospatial,
      memory and executive functions.

PMID- 22872309
TI  - 90Y-based PET and SPECT/CT imaging in locoregional brain treatment for high-grade
      gliomas: retrospective fusion with MRI.

PMID- 22872311
TI  - Evaluating socioeconomic and racial differences in traffic-related metrics in the
      United States using a GIS approach.
AB  - Previous studies have reported that lower-income and minority populations are
      more likely to live near major roads. This study quantifies associations between
      socioeconomic status, racial/ethnic variables, and traffic-related exposure
      metrics for the United States. Using geographic information systems (GIS),
      traffic-related exposure metrics were represented by road and traffic densities
      at the census tract level. Spearman's correlation coefficients estimated
      relationships between socio-demographic variables and traffic-related exposure
      metrics, and ANOVA was performed to test for significant differences in socio
      demographic variables for census tracts with low and high traffic-related
      metrics. For all census tracts in the United States, %Whites, %Blacks, and
      %Hispanics (percent of tract population) had correlation coefficients greater
      than 0.38 and 0.16 with road density and traffic density, respectively. Regions
      and states had correlation coefficients as high as 0.78. Compared with tracts
      with low road and traffic densities (<25th percentile), tracts with high
      densities (>75th percentile) had values of %Blacks and %Hispanics that were more
      than twice as high, 20% greater poverty levels, and one-third fewer White
      residents. Census tracts that had mid-level values for road and traffic densities
      had the most affluent characteristics. Results suggest that racial/ethnic and
      socioeconomic disparities exist on national level with respect to lower-income
      and minority populations living near high traffic and road density areas.

PMID- 22872310
TI  - Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal
      carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase
      arrest.
AB  - PURPOSE: Targeted therapy with alpha-particle emitting radionuclides is a
      promising new option in cancer therapy. Stable conjugates of the vascular tumour
      homing peptide F3 with the alpha-emitter (213)Bi specifically target tumour
      cells. The aim of our study was to determine efficacy of combined (213)Bi
      diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to
      treatment with either (213)Bi-DTPA-F3 or paclitaxel both in vitro and in vivo.
      METHODS: Cytotoxicity of treatment with (213)Bi-DTPA-F3 and paclitaxel, alone or
      in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the
      clonogenic assay and flow cytometric analyses of the mode of cell death and cell
      cycle arrest. Therapeutic efficacy of the different treatment options was assayed
      after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft
      tumours. Therapy monitoring was performed by bioluminescence imaging and
      histopathologic analysis. RESULTS: Treatment of OVCAR-3 cells in vitro with
      combined (213)Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity,
      induction of apoptosis and G2/M phase arrest compared to treatment with either
      (213)Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed
      the best response following repeated (six times) combined therapy with (213)Bi
      DTPA-F3 (1.85 MBq) and paclitaxel (120 MUg) as demonstrated by bioluminescence
      imaging and histopathologic investigation of tumour spread on the mesentery of
      the small and large intestine. Moreover, mean survival of xenograft mice that
      received combined therapy with (213)Bi-DTPA-F3 and paclitaxel was significantly
      superior to mice treated with either (213)Bi-DTPA-F3 or paclitaxel alone.
      CONCLUSION: Combined treatment with (213)Bi-DTPA-F3 and paclitaxel significantly
      increased mean survival of mice with peritoneal carcinomatosis of ovarian origin,
      thus favouring future therapeutic application.

PMID- 22872312
TI  - Bimetallic catalysts for upgrading of biomass to fuels and chemicals.
AB  - Research interest in biomass conversion to fuels and chemicals has increased
      significantly in the last decade as the necessity for a renewable source of
      carbon has become more evident. Accordingly, many different reactions and
      processes to convert biomass into high-value products and fuels have been
      proposed in the literature. Special attention has been given to the conversion of
      lignocellulosic biomass, which does not compete with food sources and is widely
      available as a low cost feedstock. In this review, we start with a brief
      introduction on lignocellulose and the different chemical structures of its
      components: cellulose, hemicellulose, and lignin. These three components allow
      for the production of different chemicals after fractionation. After a brief
      overview of the main reactions involved in biomass conversion, we focus on those
      where bimetallic catalysts are playing an important role. Although the reactions
      are similar for cellulose and hemicellulose, which contain C(6) and C(5) sugars,
      respectively, different products are obtained, and therefore, they have been
      reviewed separately. The third major fraction of lignocellulose that we address
      is lignin, which has significant challenges to overcome, as its structure makes
      catalytic processing more challenging. Bimetallic catalysts offer the possibility
      of enabling lignocellulosic processing to become a larger part of the biofuels
      and renewable chemical industry. This review summarizes recent results published
      in the literature for biomass upgrading reactions using bimetallic catalysts.

PMID- 22872313
TI  - Myocardial contrast echocardiography for simultaneous assessment of function and
      perfusion in real time: a technique comes of age.

PMID- 22872314
TI  - Prognostic value of high-dose dipyridamole stress myocardial contrast perfusion
      echocardiography.
AB  - BACKGROUND: The addition of myocardial perfusion (MP) imaging during dipyridamole
      real-time contrast echocardiography improves the sensitivity to detect coronary
      artery disease, but its prognostic value to predict hard cardiac events in large
      numbers of patients with known or suspected coronary artery disease remains
      unknown. METHODS AND RESULTS: We studied 1252 patients with the use of
      dipyridamole real-time contrast echocardiography and followed them for a median
      of 25 months. The prognostic value of MP imaging regarding death and nonfatal
      myocardial infarction was determined and related to wall motion (WM), clinical
      risk factors, and rest ejection fraction by the use of Cox proportional-hazards
      models, C index, and risk reclassification analysis. A total of 59 hard events
      (4.7%) occurred during the follow-up (24 deaths, 35 myocardial infarctions). The
      2-year event-free survival was 97.9% in patients with normal MP and WM, 91.9%
      with isolated reversible MP defects but normal WM, and 67.4% with both reversible
      MP and WM abnormalities (P<0.001). By multivariate analysis the independent
      predictors of events were age (hazard ratio 1.05, 95% confidence interval [CI],
      1.02-1.08), sex (hazard ratio, 2.36; 95% CI, 1.32-4.23), reversible MP defects
      (hazard ratio, 3.88; 95% CI, 1.83-8.21), and reversible WM abnormalities with
      reversible MP defects (hazard ratio, 4.51; 95% CI, 2.25-9.07). Reversible MP
      defects added incremental predictive value and reclassification benefit over WM
      response and clinical factors (P=0.001). CONCLUSIONS: MP imaging using real-time
      perfusion echocardiography during dipyridamole real-time contrast
      echocardiography provides independent, incremental prognostic information
      regarding hard cardiac events in patients with known or suspected coronary artery
      disease. Patients with normal MP responses have better outcome than patients with
      normal WM; patients with both reversible WM and MP abnormalities have the worst
      outcome.

PMID- 22872315
TI  - Novel pHEMA-gelatin SPHs as bone scaffolds in dynamic cultures.
AB  - The effectiveness of poly(2-hydroxyethyl methacrylate)-gelatin superporous
      hydrogels (pHEMA-gelatin SPHs) was investigated for bone tissue engineering. The
      cell culture studies were performed with preosteoblastic MC3T3-E1 cells. Dynamic
      culture conditions were provided using 100 ml spinner flask rotating at 50 rpm.
      According to the results of mitochondrial activity test (1-3-[4,5-dimethylthiazol
      2-yl]-diphenyltetrazolium bromide), there is no significant difference between
      proliferation behavior of cells cultured under static and dynamic conditions
      during 28 days. Observations by scanning electron microscopy and confocal laser
      scanning microscopy showed that, cells attached well onto the scaffolds and
      spread through the pores for both culture conditions. However, it was found that,
      calcium deposition and alkaline phosphatase activity in the scaffolds cultured
      under dynamic conditions were higher than that of static conditions. The
      expression of osteogenic differentiation markers, i.e. collagen I and
      osteopontin, based on real-time reverse transcriptase-polymerase chain reaction
      demonstrated increased responses under the spinner flask culture conditions. The
      combination of dynamic culture conditions in spinner flask with the use of
      superporous pHEMA-gelatin scaffolds enhanced the outcomes related to bone tissue
      engineering.

PMID- 22872316
TI  - On the ultrastructural organization of Trypanosoma cruzi using cryopreparation
      methods and electron tomography.
AB  - The structural organization of Trypanosoma cruzi has been intensely investigated
      by different microscopy techniques. At the electron microscopy level, bi
      dimensional analysis of thin sections of chemically fixed cells has been one of
      the most commonly used techniques, despite the known potential of generating
      artifacts during chemical fixation and the subsequent steps of sample
      preparation. In contrast, more sophisticated and elaborate techniques, such as
      cryofixation followed by freeze substitution that are known to preserve the
      samples in a more close-to-native state, have not been widely applied to T.
      cruzi. In addition, the 3D characterization of such cells has been carried out
      mostly using 3D reconstruction from serial sections, currently considered a low
      resolution technique when compared to electron tomography (ET). In this work, we
      re-visited the 3D ultrastructure of T. cruzi using a combination of two
      approaches: (1) analysis of both conventionally processed and cryofixed and
      freeze substituted cells and (2) 3D reconstruction of large volumes by serial
      electron tomography. The analysis of high-pressure frozen and freeze substituted
      parasites showed novel characteristics in a number of intracellular structures,
      both in their structure and content. Organelles generally showed a smooth and
      regular morphology in some cases presenting a characteristic electron dense
      content. Ribosomes and new microtubule sets showed an unexpected localization in
      the cell body. The improved preservation and imaging in 3D of T. cruzi cells
      using cryopreparation techniques has revealed some novel aspects of the
      ultrastructural organization of this parasite.

PMID- 22872317
TI  - Syndecan-4 is associated with beta-cells in the pancreas and the MIN6 beta-cell
      line.
AB  - Basement membranes (BM) in the pancreatic islet are important for islet survival
      and function, but supplementation of isolated islets with these components have
      had limited success. Currently, little is understood about which BM components
      and proteoglycans are essential to maintaining islet homeostasis. This study
      therefore aimed to characterize the BM components and proteoglycans of the islet
      in the mouse, rat and rabbit species. The BM of the mouse islet was varied in
      continuity around the islet and was discontinuous in the rat and rabbit islets.
      The BM consisted of collagen IV, laminin, fibronectin and perlecan in the mouse
      and was in tight association with the underlying islet endothelium. None of these
      components were found directly associated with the beta-cells in tissue and in
      the MIN6 beta-cell line. In contrast, heparan sulfate (HS) was distributed
      throughout the islet in all three species in a pattern distinctly different to
      that of perlecan and was observed mainly on the beta-cells and not the alpha
      cells in the mouse and rat. Similarly, syndecan-4 showed a staining pattern
      almost identical to that of HS and was mostly observed on the beta-cells, not
      alpha-cells, in the mouse and rat. Both HS and syndecan-4 were also observed in
      the MIN6 beta-cell line. The mouse islet and MIN6 syndecan-4 were both ~37 kDa in
      size, after deglycosylation with heparitinase. These results indicate that
      syndecan-4 may play an important role in beta-cell function and that the cell
      surface HS proteoglycans may be the missing link to maintaining islet longevity
      after isolation.

PMID- 22872318
TI  - Fluorescent analogs of the marine natural product psammaplin A: synthesis and
      biological activity.
AB  - The symmetrical disulfide psammaplin A from the marine sponge Pseudoceratina sp.
      was synthesized and structurally altered by replacement of one of the alpha
      (hydroxyimino)acyl units by a fluorescent 4-coumarinacetyl moiety. Thus, the
      first fluorescent analogs of psammaplin A were obtained. Structural variation
      also covered the substitution pattern of the phenyl ring. Cytotoxicity of
      psammaplin A against the mouse fibroblast cell line L-929 (IC(50) 0.42 MUg mL(
      1)) was about two-fold higher than that of the fluorescent hybrid compounds,
      whereas the disulfide containing two 4-coumarinacetyl moieties was inactive.
      Fluorescence microscopy revealed uptake of the 4-coumarinacetyl-alpha
      (hydroxyimino)acyl hybrids into the cytoplasm leading to fluorescence in close
      proximity of the nuclear envelope, most likely in the Golgi apparatus. We did not
      observe strong fluorescence inside the nucleus, where most of the target histone
      deacetylases are located. We conclude that reduction of the disulfide probably
      takes place outside the nucleus. The psammaplin-derived thiol exhibited potent
      activity against histone deacetylase in the low nanomolar range, but diminished
      cytotoxicity. Antimicrobial activity of the new derivatives was also determined.

PMID- 22872319
TI  - Comparison of nitrate augmented Tc-99m tetrofosmin gated SPECT imaging with FDG
      PET imaging for the assessment of myocardial viability in patients with severe
      left ventricular dysfunction.
AB  - BACKGROUND: Of various nuclear medicine techniques, F-18/flourodeoxyglucose (FDG)
      positron emission tomography (PET) is considered as the best modality for the
      assessment of viable myocardium (VM). In this study, we compared the diagnostic
      accuracy of nitrate augmented Tc-99m tetrofosmin gated G-single-photon emission
      computed tomography (SPECT) with FDG PET. METHODS: 54 consecutive cases of
      angiographically proven CAD with severe LV dysfunction were enrolled in the
      study. The patients underwent Tc-99m tetrofosmin G-SPECT and FDG PET as per the
      standard protocols and were compared. RESULTS: SPECT data analysis indicated
      functional abnormalities in 661/918 myocardial segments. F-18 FDG PET revealed VM
      in 496/661 segments. The diagnostic accuracy of baseline NAC, postnitrate NAC,
      baseline AC, and postnitrate AC Tc-99m tetrofosmin SPECT was 84%, 87%, 90%, and
      94%, respectively. kappa values for NAC baseline, NAC postnitrate, AC baseline,
      and AC postnitrate Tc-99m tetrofosmin G-SPECT were 0.65, 0.70, 0.77, and 0.85,
      respectively. Attenuation correction revealed viability additionally in 46
      segments which were non-viable on NAC postnitrate study (P < .001). Nitrate
      augmentation showed viability additionally in 25 segments which were non-viable
      on AC baseline scan (P = .004). On patient-based analysis FDG PET changes the
      management only in 13% (7/54) of patients. CONCLUSIONS: Nitrate augmented AC Tc
      99m tetrofosmin G-SPECT shows excellent (kappa = .85) agreement with FDG PET. FDG
      PET changes management only in 13% of the patients. Tc-99m tetrofosmin G-SPECT
      being more widely available and cheaper imaging modality can be reliably used to
      detect VM where FDG PET is not available.

PMID- 22872320
TI  - Secretion of matrix metalloproteinase-9 from astrocytes by inhibition of tonic
      P2Y14-receptor-mediated signal(s).
AB  - Glial cells have various important roles in regulation of brain functions. For
      such events, extracellular nucleotides/P2 receptors have central roles. Although
      there have been huge amount of literature about activation of P2 receptors and
      glial functions, little is known about what happens in glia or the brain if glial
      P2 receptor is inhibited. Here we show that the inhibition of P2 receptors in
      astrocytes, the most abundant glial cells and cause a constitutive release of
      nucleotides, resulted in secretion of metalloproteinase-9 (MMP-9), a metal
      dependent endopeptidase that degrades extracellular matrix molecules and is
      important in regulation of brain remodeling. When cultured astrocytes were
      treated with apyrase (ecto-nucleotidase), reactive blue 2 (P2 receptor
      antagonist), and pertussis toxin, they secreted MMP-9, suggesting that Gi-coupled
      P2Y receptor-mediated signals constitutively suppress the production of MMP-9.
      Among Gi-coupled P2Y receptors, we found that an inhibition of P2Y(14) receptor,
      a receptor for nucleotide-sugars such as UDP-glucose, is responsible for the
      production of MMP-9 by pharmacological and molecular biochemical analysis. As for
      the mechanisms, the inhibition of P2Y(14) receptors resulted in the release of
      tumor necrosis factor (TNF)-alpha which then acted on astrocytes to induce MMP-9.
      Taken together, our results suggest that the constitutive releases of nucleotide
      sugars in astrocytes should play an important role in maintaining the normal
      status of the cell, through Gi-coupled P2Y(14) receptors, and when the signal is
      removed, the cells start to release TNF-alpha, which then acts on astrocytes in a
      feedback fashion to boost MMP-9 synthesis and secretion.

PMID- 22872321
TI  - A mechanism for nerve cell excitation by norepinephrine via alpha-1
      adrenoceptors: inhibition of potassium M-current.
AB  - Some of the excitatory effects of norepinephrine on central neurons are mediated
      by alpha-1 (alpha1) adrenoceptors. These receptors are coupled to the Gq family
      of G proteins, and hence stimulate hydrolysis of the membrane phospholipid
      phosphatidylinositol-4,5-bisphosphate. Other receptors of this type can excite
      neurons by inhibiting the subthreshold voltage-gated potassium M-current. We
      tested this possibility using rat sympathetic neurons transformed to express
      alpha1a receptors. The alpha1 agonist phenylephrine strongly inhibited the M
      current recorded under voltage-clamp by 72 +/- 11 % (n = 4) and in an unclamped
      neuron dramatically increased the number of action potentials produced by a 2 s
      depolarizing current step from 2 to 40, without effect on control neurons devoid
      of alpha1 receptors. We suggest that this might be a potential cause of the
      increased excitability produced by norepinephrine in some central neurons.

PMID- 22872322
TI  - Enhanced sensitivity of skeletal muscle growth in offspring of mice long-term
      selected for high body mass in response to a maternal high-protein/low
      carbohydrate diet during lactation.
AB  - AIM: To investigate the effects of a high-protein/low-carbohydrate diet fed to
      mice of different genotypes during pregnancy and/or lactation on offspring
      skeletal muscle growth and metabolism. METHODS: Pregnant mice from strains
      selected for high body mass (DU6) or endurance running performance (DUhLB) and
      from an unselected control strain (DUK) were fed iso-energetic diets containing
      20 % (C) or 40 % protein and low carbohydrate (HP) from mating to weaning at day
      21 of age. At birth, offspring were cross-fostered resulting in different
      exposure to maternal prenatal-preweaning diets (C-C, HP-C, C-HP, HP-HP). Rectus
      femoris muscle of male mice (n = 291) was examined at day 23, 44, 181 and 396 of
      age for cellular growth and metabolism. RESULTS: At day 23 of age, body and
      muscle growth was retarded by 30-40 % (P < 0.0001) in response to the C-HP and HP
      HP, but not to the HP-C diet, due to reduced fibre size (P < 0.0001) but not
      fibre number. DNA was highly reduced in DU6, less in DUhLB, but not in DUK muscle
      (strain * diet; P < 0.0001). Despite some compensation, muscle growth was still
      impaired (P < 0.001) in adulthood (day 44; day 181), but at senescence only in
      DU6 mice (strain * diet; P < 0.05). Only at weaning, isocitrate and lactate
      dehydrogenase activities were increased or decreased (P < 0.0001), respectively,
      without influence on fibre type composition. CONCLUSION: A high-protein/low
      carbohydrate diet fed to dams during lactation, but not during pregnancy, retards
      skeletal muscle growth in offspring with greater response of a heavy, obese
      compared with a physically fit and a control genotype and causes a transient
      shift towards oxidative versus glycolytic muscle metabolism.

PMID- 22872324
TI  - No benefit and potential harm with an educational and care management programme
      for chronic obstructive pulmonary disease.

PMID- 22872323
TI  - Beneficial effects of polyphenol-rich olive oil in patients with early
      atherosclerosis.
AB  - PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or
      catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the
      incidence of cardiovascular diseases, potentially by improving endothelial
      function, an important surrogate for atherosclerosis. The possible augmentation
      of endothelial function with the combined efforts of OO and EGCG is intriguing,
      yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of
      endothelial dysfunction) were enrolled in this double-blind, randomized trial
      with 52 completing the study. The aim of the study was to compare the effect of a
      daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on
      endothelial function as well as on inflammation and oxidative stress after a
      period of 4 months. Endothelial function was assessed noninvasively via
      peripheral arterial tonometry (Endo-PAT(r)). RESULTS: After 4 months, when OO and
      EGCG-supplemented OO groups were combined, OO significantly improved endothelial
      function (RHI, 1.59 +/- 0.25-1.75 +/- 0.45; p < 0.05). However, there were no
      significant differences in results between the two olive oil groups.
      Interestingly, with OO supplementation there was a significant reduction in
      inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells
      (WBCs) (6.0 * 109/L-5.8 * 109/L, p < 0.05); monocytes (0.48 * 109/L to 0.44 *
      109/L, p = 0.05); lymphocytes (1.85 * 109/L to 1.6 * 109/L, p = 0.01); and
      platelets (242-229 * 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial
      dysfunction in patients with early atherosclerosis in association with
      significant reduction in leukocytes may suggest an important role of early
      cellular inflammatory mediators on endothelial function. The current study
      supports one potential mechanism for the role of olive oil, independent of EGCG,
      modestly supplemented to a healthy cardiovascular diet.

PMID- 22872325
TI  - [Itineraries and methods of illegal abortion in five Brazilian state capitals].
AB  - This paper presents the results of the structured interview phase of the National
      Abortion Survey (PNA-interviews), describing the itineraries, methods and social
      and demographic profile of women who had at least one illegal abortion.
      Structured interviews were conducted during the years 2010 and 2011 in five state
      capitals (Belem, Brasilia, Porto Alegre, Rio de Janeiro and Salvador) with 122
      women aged between 18 and 39 who had abortions. It is a non-probabilistic sample
      controlled by six parameters in accordance with level of education and age to
      reflect the social and demographic structure found in the PNA ballot-box
      questionnaire phase. The majority of women interviewed had had only one abortion,
      but 1 in every 4 had two abortions and 1 in every 17 had a third one. The
      majority of abortions are among women under 19 years of age who already had
      children and a higher incidence is found among black women. The most common test
      for pregnancy is beta-HCG blood test, the pharmacy urine test and ultrassound.
      The prevailing method for induction is a combination of teas and misoprostol
      (called Cytotec in Brazil), followed by hospital assistance after induction.
      Women are usually helped by a relative or their partners and several women
      reported helping other women to have abortions.

PMID- 22872326
TI  - [Comments on the article: Itineraries and methods of illegal abortion in five
      Brazilian state capitals].

PMID- 22872327
TI  - [The legal and social consequences of maintaining the criminalization of
      abortion].

PMID- 22872328
TI  - [On the swallowed and hidden fetuses: a comment about the support of riverside
      midwives for abortion].

PMID- 22872330
TI  - ["Those of you who have never had an abortion, raise your hand!" Rethinking
      ethnographic data on the dissemination of abortion practices among low-income
      populations in Brazil].
AB  - Based on recently published research findings on abortion rates, this paper re
      examines original ethnographic data on abortion in order to open a discussion on
      the dissemination of abortion, its possible cultural configurations and its
      social legitimacy among low-income populations in Brazil. It refers
      retrospectively to two works of empirical research studies and presents an
      estimate of the prevalence of abortion of around of 34%; it describes abortion
      practices and the social representation of what abortion means in a given
      context. The studies presented here seek to contribute to the understanding of
      women's decision-making regarding this reproductive choice in a context where
      abortion is illegal. The data allow us to construct an abortion typology,
      classifying it as tolerated, unacceptable and recommended and point to a fluidity
      of meanings regarding pregnancy interruption practices. It is possible to infer
      that the magnitude of the problem of abortion, both with regard to number of
      cases and the existing diversity of abortion practices and methods, has not
      changed over a period of 20 years in Brazil.

PMID- 22872331
TI  - [Abortion itineraries in a clandestine context in the city of Rio de Janeiro
      Brazil].
AB  - From a series of in-depth interviews, we gathered a significant amount of
      ethnographic material on the concrete and symbolic paths taken by young women and
      their partners in the search for a solution to an unplanned pregnancy. Inequities
      in Brazilian society are expressed in itineraries/routes of different sinuosity,
      complexity and duration according to the individuals' social and material
      conditions of existence. Thus, for middle class youths access to abortion is very
      swift and secure, whereas for the rest of women the decision to abort consists of
      efforts on different levels to achieve the undertaking. The narratives may assume
      dramatic proportions, including abortion even in advanced stages of pregnancy.

PMID- 22872332
TI  - [Motives and circumstances surrounding induced abortion among women living with
      HIV in Brazil].
AB  - The impact of HIV/AIDS infection on the decision of women living with HIV/AIDS to
      interrupt a pregnancy remains an understudied topic. In an effort to understand
      the influence of HIV/AIDS diagnosis on abortion practices, a qualitative study
      was carried out in seven Brazilian municipalities with women living with HIV/AIDS
      who reported inducing an abortion at some point in their lives. This study
      presents the analysis of interviews with thirty women who became pregnant after
      diagnosis. The results show that for some women, infection was the primary motive
      for terminating their pregnancy, while for others, the motives for abortion were
      predominantly related to life circumstances. The decision to abort due to HIV
      infection is not the same for all women. It is related to the timing of the
      diagnosis and other aspects of the woman's life during her pregnancy, such as the
      relationship with her partner, her job and family support. The results suggest
      the need for more attention from health services to the reproductive decisions of
      women living with HIV/Aids; the incorporation of men into sexual and reproductive
      health prevention actions; and a deeper discussion of the illegality of abortion
      in Brazil and its harmful consequences for women, men, and children.

PMID- 22872333
TI  - Recommendations for abortion surveys using the ballot-box technique.
AB  - The article lists recommendations for dealing with methodological aspects of an
      abortion survey and makes suggestions for testing and validating the survey
      questionnaire. The recommendations are based on the experience of the Brazilian
      Abortion Survey (PNA), a random sample household survey that used the ballot-box
      technique and covered adult women in all urban areas of the country.

PMID- 22872334
TI  - [Induced abortion: a comparison between married and single women residing in the
      city of Sao Paulo in 2008].
AB  - The scope of this study was to evaluate the association between having had an
      induced abortion and marital status (being single or legally married) in women
      residing in the city of Sao Paulo. This analysis is derived from a broader
      population survey on abortion conducted in 2008. In this study we focus on the
      subset of 389 single and legally married women between 15 and 49 years of age.
      Logistic regression models were used to evaluate the association between induced
      abortion and being single or married, monitoring age, education, income, number
      of live births, contraceptive use and acceptance of the practice of abortion.
      Being single was the only characteristic associated with having had an induced
      abortion, in other words, when faced with a pregnancy single women were four
      times more likely to have an abortion than married women (OR=3.9; p=0.009).

PMID- 22872335
TI  - [Induced abortion among prostitutes: a survey using the ballot-box technique in
      Teresina-Piaui].
AB  - This study assesses the prevalence of induced abortion among prostitutes and
      lists the most common abortion practices. A survey was conducted with 310
      prostitutes between 18 and 39 years of age, by sampling age quotas in the 5
      territorial areas of Teresina in the state of Piaui. Data collection was
      conducted through the use of 2 questionnaires: the first, by the ballot-box
      technique, with questions about abortion; the second, completed by the
      researcher, with socio-demographic information. The practice of abortion was
      reported by 163 (52.6%) women. Most prostitutes performed 1 abortion (50.3%), but
      16.5% of them reported carrying out 3 or more. Misoprostol was used alone in
      68.1% of the reports and associated with tea and/or probes in 9.2%, followed by
      tea in 13.4%, probes in 3.7%, and uterine curettage in unregulated clinics in
      3.7%. There was post-abortion hospitalization in 47.8% of the cases. After
      adjustment of the multiple logistic regression model, the variable that remained
      significantly associated with abortion was to have had 3 or more pregnancies.
      These results revealed that induced abortion is an event of great prevalence
      among prostitutes in Teresina. Misoprostol is the most common method to abort and
      hospitalization was necessary in almost half of cases.

PMID- 22872336
TI  - [Representations and experiences of obstetrician/gynecologists with legal and
      illegal abortion in two maternity-hospitals in Salvador da Bahia].
AB  - The objective of this qualitative study, carried out in two maternity-hospitals
      in Salvador da Bahia, was to investigate the experience and representations of
      health professionals, and particularly obstetricians-gynecologists, regarding
      legal abortion in comparison with their representations and experience with
      illegal abortion. A questionnaire was distributed and semi-structured interviews
      were conducted with 25 health professionals (13 obstetricians-gynecologists) in a
      hospital providing legal abortion (P) and with 20 health professionals (9
      obstetricians-gynecologists) in another hospital that does not provide this
      service (F). The factors that influence the representations and experience of
      abortion of most obstetricians-gynecologists and explain the high rate of
      conscientious objection at Hospital P were: 1- the criminalization of abortion
      and the fear of being denounced; 2- the stigmatization of abortion by certain
      religious groups and by the physicians themselves; 3- training in obstetrics and
      the lack of good training in the epidemiology of maternal morbidity-mortality and
      abortion; 4- representations on gender relations. The main factors associated
      with liberal attitudes were: age - under 30 and over 45 years of age - experience
      with high maternal mortality rates due to abortion and experience with legal
      abortion.

PMID- 22872337
TI  - [Practice in situations of legal abortion from the perspective of health
      professionals at Fernando Magalhaes public hospital].
AB  - The scope of this study was to analyze perceptions of health professionals at
      Fernando Magalhaes Public Hospital regarding situations involving the practice of
      legal abortion. With this in mind, we sought to characterize the professionals
      interviewed, understand the qualifying process for assistance of women requiring
      abortion and identify the perceptions of the professionals regarding the practice
      of legal abortion. The quantitative and qualitative approach in terms of
      methodology was adopted. The instruments used were analysis of institutional
      documentation and semi-structured interviews based on a script with informed
      consent. The results of this research revealed: the inappropriate use of the
      right to conscientious objection by health professionals; the existence of
      difficulties faced by professionals in construction of a posture that ensures
      access to legally sanctioned abortion; and the interference of ethical and
      religious values as an important element in professional attitudes that
      discourage the practice of legal abortion. Measures for the ongoing education of
      professionals and the monitoring of actions applied to technical norms are
      recommended.

PMID- 22872338
TI  - [Quality of abortion care in the Unified Health System of Northeastern Brazil:
      what do women say?].
AB  - Abortion is a serious health problem in Brazil and complications can be avoided
      by adequate and timely care. The article evaluates the quality of care given to
      women admitted for abortion in hospitals operated by the Unified Health System,
      in Salvador, Recife and Sao Luis, the benchmarks being Ministry of Health norms
      and user satisfaction. The article analyzes 2804 women admitted to hospital for
      abortion complications in 19 hospitals, between August and December 2010. Four
      dimensions were defined: reception and guidance; inputs and physical environment;
      technical quality and continuity of care. There was a closer fit to norms on
      reception and guidance. Social support and the right to information were not well
      rated in all three cities. The technical quality of care was rated poor. With
      respect to inputs and physical environment, cleanliness was the least adequate
      criterion. Continuity of care was the most critical situation in all three
      cities, due to the lack of scheduled follow-up appointments, information about
      care available after hospital discharge, the risk of further pregnancy and family
      planning. Abortion care falls short of that advocated under Brazilian norms and
      by international agencies.

PMID- 22872339
TI  - [Abortion and misoprostol: health practices and scientific controversy].
AB  - This article puts into perspective the controversy between the association of the
      use of misoprostol for abortion and teratogenicity studies of the type found in a
      case report. The use of herbal medicinal drugs and the medical-obstetric and
      national and international norms governing the registration and circulation of
      pharmaceutical products were examined. Official documents of ANVISA, the Ministry
      of Health and the World Health Organization on the use of misoprostol, as well as
      68 articles such as case reports published in national journals, linking
      abortion, misoprostol and teratogenicity were reviewed, systematically filed and
      analyzed using the monographic method. The legal prohibition of abortion prevents
      the proper prescription and use of a drug such as misoprostol that is both safe
      and effective. Thus, the danger for the health of women is linked not to the
      intrinsic characteristics of the drug, but to the moral arguments that constitute
      negligence and disregard for the fundamental rights of women.

PMID- 22872340
TI  - [Misoprostol: pathways, mediation and social networks for access to abortion
      using medication in the context of illegality in the State of Sao Paulo].
AB  - The scope of this article is to discuss the commercialization and use of
      misoprostol for abortion purposes in the illegal contexts that still persist in
      Brazil. The information presented was collected through case studies conducted
      with two young women who aborted using medication - one successfully and one
      unsuccessfully - and two adult women who have close ties with women who used
      misoprostol. The study confirms the hypothesis that the diffusion and expansion
      of the use of misoprostol outside the hospital context is associated with the
      decision of women who seek lower costs, lower risks to their health and privacy.
      It also permits examination of the interpretation that this increase in
      consumption is linked to the inclusion of the medication in a set of goods that
      are illegally traded in Brazil, in different ways and in different contexts. As a
      result, women are exposed to different degrees of vulnerability depending
      directly on the steps taken, types of mediation used and social networks they
      belong to. These are the ways in which women and men obtain access to the use of
      misoprostol for abortion, the outcome of which may be successful or not.

PMID- 22872341
TI  - [Cytotec and abortion: the police, the vendors and women].
AB  - This paper analyzes the illegal trade in misoprostol, the medication
      predominantly used for abortion in Brazil. The study analyzed ten cases that came
      to the attention of the Public Prosecution Service for the Federal District
      between 2004 and 2010. The cases were organized into three categories: 1. women's
      stories; 2. profile of the vendors; 3. maternal mortality cases. The research was
      reviewed by an ethics committee. The main outcomes were: 1. young women in steady
      relationships use misoprostol in the home or with the assistance of drug vendors.
      Of the seven women indicted, three were reported on arrival at the public
      hospital to finalize abortion; 2. the drug vendors work at the community
      drugstore and are local agents for the sale of misoprostol. They instruct women
      on how to use the drug and how to prevent infections, but refuse to provide them
      with care in case of emergency. Traffickers operate via the internet and have a
      larger inventory of drugs; 3. there were two cases of maternal mortality due to
      the combination of high risk methods, such as a vaginal probe and misoprostol.
      The main causes for maternal mortality are the delay in seeking medical care, as
      the women fear criminal prosecution, and the combined use of misoprostol with
      high risk methods.

PMID- 22872342
TI  - [The stance of abortion in the Brazilian printed media ahead of the 2010
      presidential elections: the exclusion of public health from the debate].
AB  - OBJECTIVES: this article presents the results of research to monitor the
      Brazilian printed media in order to identify the stance of the abortion issue
      during the period from July 6 to October 29, 2010, which was the period of the
      official presidential campaign in Brazil. METHODOLOGY: based on the monitoring of
      28 printed media vehicles (newspapers and magazines) with nationwide circulation,
      the research selected 464 texts, of which 434 were considered valid for the
      study. The media studied included stories, reports, notes, opinion columns,
      interviews and letters from readers. RESULTS: although abortion was widely
      mentioned in Brazilian news coverage of the presidential campaign in 2010, with
      an average of four texts published per day, the stance adopted for the issue was
      not from the standpoint of public health. Among the 434 texts analyzed, only one
      report explicitly addressed epidemiological data linking abortion to women's
      health. In the other texts, the positioning of abortion was guided by the
      electoral stance that associated it with the dispute for the votes of the
      religious communities and conservative voters.

PMID- 22872343
TI  - [Participation in health: systematization of the articles published in Brazilian
      journals--1988/2005].
AB  - This is a study involving the revision of 107 papers on participation in health,
      published in 25 Public Health journals, with a view to systematize its main focus
      points and identify the options for the participation of society in the health
      system. Bibliographic research was conducted using key words, and the reading of
      abstracts of articles published in national public health journals linked to the
      CAPES portal between 1988 and 2005. The articles selected were read and
      categorized according to methodological and thematic aspects. Three dimensions
      were identified: the main dimension emphasizes participation as a strategy for
      the enhancing of citizenship and recognition of the right to health; the second
      refers to participation as a strategy for democratization of the State and
      strengthening of the health system, including participation in political,
      managerial and inspection decisions; in the third dimension of community
      participation, individuals, families and the community share the responsibility
      for health with the State. In the works examined the participation in the health
      system is still in progress and highlights its importance as an incentive for
      social capital; however, some authors point to difficulties for effective
      participation in accordance with legal propositions.

PMID- 22872344
TI  - [Health education in the user-worker relationship in the the daily routine of
      family health teams].
AB  - The scope of this research was to analyze how the practice of health education
      occurs in the informal user-worker relationship, and the strategies used for its
      implementation in routine primary care. It is a qualitative study conducted with
      two Family Health teams and the data was collected through observation and semi
      structured interviews and assessed using discourse analysis. Health education in
      the informality of professional-user relations occurs in everyday conversations
      and guidance, and permeates the various issues involving the needs of users.
      Workers present educational strategies that occur in a non-structured manner,
      some of which portray a differentiated way of implementing educational practice,
      though most of these are restricted to the transfer of information, in which
      employees seek to transfer/inform reinforcing their attitude of imposition and
      control of know-how they consider to be right. It is necessary to rethink and
      enhance health education as labor technology, which reveals different processes
      for action in health, reorienting the practice into meaningful learning, which
      promotes change among users, workers, and in the current healthcare model.

PMID- 22872345
TI  - [Accessibility for people with disabilities or permanent mobility restrictions to
      the Unified Health System].
AB  - The scope of this study was to monitor the access of persons with disabilities
      and permanent mobility restrictions to the Unified Health System in Joao Pessoa,
      State of Pernambuco. This is a descriptive field study, consisting of a random
      sample of 523 people with disabilities or permanent mobility restrictions. Data
      collection occurred between August 2007 and December 2008 and consisted of home
      interviews. The neuromusculoskeletal functions and those related to movement
      (52%) were among the most affected body functions, with a higher incidence among
      body structures related to movement (44.2%) and those of the nervous system
      (39.2%), with special emphasis on the high number of cases (14%) due to the
      sequelae from strokes. Among the respondents, 63.9% stated that there had not
      been sufficient and appropriate means to lessen the physical obstacles between
      their homes and the places where they received healthcare, and 41.7% claimed that
      there were no special facilities for the handicapped in the healthcare offices.
      Brazilian law ensures rights for people with disabilities, which were not broadly
      respected. Action is necessary to prevent the development of disabilities,
      especially those resulting from the sequelae from strokes.

PMID- 22872346
TI  - [Assessment of educational actions on the oral health of adolescents within the
      Family Health Strategy].
AB  - OBJECTIVE: to evaluate the actions of education on the oral health of adolescents
      within the scope of the Family Health Strategy. METHODOLOGY: A questionnaire was
      applied and a clinical exam conducted evaluating biofilm and gingival
      inflammation in 80 adolescents before and after interventions. A qualitative
      study of the brushing technique was also performed on 15 adolescents in the
      sample. RESULTS: there was an improvement in oral hygiene of adolescents who
      participated in actions at school and an increase in the number of adolescents
      who had healthy gums or only mild inflammation in the second test in school
      groups and home visits. With respect to the consumption of candies, both the
      weekly group and the school group saw a decrease in candy consumption between the
      first and second tests. There was an increased frequency of brushing in the
      school group. CONCLUSION: considering the importance of educational activities
      observed in this study, the process of training and joint planning of activities
      among the school staff and health professionals would appear to be important.

PMID- 22872347
TI  - [Funding, public spending and management of health resources: the current
      situation in a Brazilian state].
AB  - This article investigates the issue of funding and the decentralization process
      in order to examine the composition, application and management of resources in
      the healthcare area. The sample surveyed involved 14 municipalities in the state
      of Rio Grande do Norte, Brazil. The research involved data gathering of financial
      transfers, the municipality's own resources and primary healthcare expenses.
      Management analysis included a survey of local managers and counselors. It was
      seen that the Unified Health System is funded mainly by federal transfers and
      municipal revenues and to a far lesser extent by state resources. Funds have been
      applied predominantly in primary healthcare. The management process saw
      centralization of actions in the city governments. Municipal secretarial offices
      and councils comply partially with legislation, though they have problems with
      autonomy and social control. The results show that planning and management
      instruments are limited, due to the contradictions inherent to the institutional,
      political and cultural context of the region.

PMID- 22872348
TI  - [Exclusive breastfeeding and diarrhea hospitalization patterns between 1999 and
      2008 in Brazilian State Capitals].
AB  - The prevalence of breastfeeding has increased over the past two decades in
      Brazil, as a result of public breastfeeding policies. The scope of this paper is
      to analyze the correlation between the increase in the prevalence of
      breastfeeding and hospitalization rates due to diarrhea. It is an epidemiological
      ecological study, based on secondary data from Brazilian Capital Cities and the
      Federal District. The prevalence of breastfeeding, the number of live births, and
      cases of hospitalization due to diarrhea were compared for the years 1999 and
      2008 and the Spearman non-parametric test was used to correlate the variables.
      During the period, 1,329,618 children under one year of age in 1999 and 2008 were
      studied. The increase in the prevalence of exclusive breastfeeding among children
      under 4 months old had a negative correlation with hospitalization rates due to
      diarrhea (Rho=-0.483, p=0.014). This correlation was stronger for girls (Rho=
      0.521, p=0.008) than for boys (Rho=-0.476, p=0.016). The increase in the
      prevalence of breastfeeding between 1999 and 2008 appears to be correlated to a
      reduction in hospitalization rates due to diarrhea over the same period,
      corroborating the importance of public policies to protect, support and promote
      breastfeeding.

PMID- 22872349
TI  - [Therapeutic techniques and subjectivation in treatment with drug users].
AB  - The internment process in therapeutic communities (TC) involves a multiplicity of
      therapeutic practices and strategies geared to abstinence from drug usage.
      According to the specialists' own regulations and explicit objectives, the
      residents must not only abandon the consumption of substances but also adopt new
      practices, attitudes, emotions and significances through the use of therapeutic
      techniques that allow them to adapt to the structure of the organization that
      these institutions impose. Based on the results of the ethnographic survey
      carried out between 2009 and 2010 in three TCs of the metropolitan area of Buenos
      Aires, Argentina, the scope of this article is to analyze from a sociological and
      anthropological standpoint the "therapeutic tools" that comprise the treatment,
      the subject models that underlie these tools, the consequences that they may
      produce and their participation in the subjectivity production processes. For
      this purpose, we focus on analysis of "confrontation" as a privileged and
      omnipresent strategy of subjectivation in these therapeutic contexts, in order to
      reveal the epistemological, economic, political and ethical dimensions in the de
      subjectivation process of the institutionalized drug user.

PMID- 22872350
TI  - [Organization of health services and tuberculosis care management].
AB  - The scope of this study was to analyze the discourse of managers regarding the
      relationship between the organization of the health services and tuberculosis
      care management in a city in the metropolitan region of Joao Pessoa, State of
      Pernambuco. Using qualitative research in the analytical field of the French line
      of Discourse Analysis, 16 health workers who worked as members of the management
      teams took part in the study. The transcribed testimonials were organized using
      Atlas.ti version 6.0 software. After detailed reading of the empirical material,
      an attempt was made to identify the paraphrasic, polyssemic and metaphoric
      processes in the discourses, which enabled identification of the following
      discourse formation: Organization of the health services and the relation with TB
      care management: theory and practice. In the discourse of the managers the
      fragmentation of the actions of control of tuberculosis, the lack of articulation
      between the services and sectors, the compliance of the specific activities for
      TB, as well as the lack of strategic planning for management of care of the
      disease are clearly revealed. In this respect, for the organization of the health
      services to be effective, it is necessary that tuberculosis be considered a
      priority and acknowledged as a social problem in the management agenda.

PMID- 22872352
TI  - [Childbirth in Cuba: analysis of the experience of medically supervised delivery
      from an anthropological perspective].
AB  - Knowledge about pregnancy, childbirth, and postpartum in Cuba is currently
      deficient. Childbirth has been fundamentally studied as a medical event from its
      clinical aspects. Analysis of the reproductive process from the Medical
      Anthropology perspective could contribute to healthcare services providing more
      humane treatment and empowerment for women and men as the persons primarily
      responsible for their reproductive processes. This study investigated the
      experience and perception of childbirth in three hospitals in Havana. The scope
      of this research was to understand the representation and practice of childbirth
      and to describe the experiences of women during this event. Qualitative
      investigation techniques were used, together with interviews and participant
      observation of 36 women in labor, ten family members and nine obstetricians. The
      qualitative data was analyzed using Grounded Theory methodology. All the
      childbirths occurred with numerous medical interventions and the maternity
      experience was very intense. The participation of men was limited. From the
      anthropological perspective the routine use of some medical interventions and the
      institutional regulations described are considered manifestations of physical and
      gender violence.

PMID- 22872351
TI  - [Adherence to drug treatment among registered users in the "HIPERDIA" Program in
      Teresina in the State of Piaui].
AB  - Arterial hypertension and diabetes mellitus are among the most chronic diseases
      prevalent in Brazil. The study sought to evaluate the socioeconomic profile and
      the therapeutic adherence of users registered in the HIPERDIA Program in Teresina
      in the State of Piaui. This research was conducted in the Primary Healthcare
      Units, where a questionnaire was given to four hundred people evaluating their
      adherence based on the Batalla and Morisky-Green tests. The socioeconomic profile
      of interviewees was as follows: senior citizens, women, married with 1 to 4 years
      of study, pensioners and salaried employees. Only 22.5% of hypertensive and 30.7%
      of diabetic interviewees were considered adherents according to Batalla, and
      among all of them only 26.75% were adherents according to Morisky-Green. There
      was no association between sociodemographic and clinical variables and adherence
      according to Morisky-Green, however there was an association with the type of
      morbidity presented. In light of these results, health education is the main
      strategy to improve adherence of users as well as the participation of
      professionals in the Family Healthcare Team, including the pharmacist, the
      nutritionist and the physical trainer.

PMID- 22872353
TI  - [Decentralization and regionalization: dynamics and conditioning factors for the
      implementation of the Health Pact in Brazil].
AB  - Decentralization and regionalization represent constitutional guidelines for the
      organization of the Unified Health System, which in the last 20 years has
      required the adoption of mechanisms to coordinate and accommodate federative
      tensions in Brazil's healthcare sector. This paper analyzes the national
      implementation of the Health Pact between 2006 and 2010 involving a strategy that
      reconfigures intergovernmental relations in the sector. The study involved the
      analysis of documents, official data and interviews with federal, state and
      municipal managers in the Brazilian states. The content of the national proposal
      is initially discussed, including its implications for health policy. The
      different rhythms and degrees of implementation of the Health Pact are then
      reviewed, with respect to adherence by states and municipalities and the
      formation of Regional Management Boards. Lastly, the conditioning factors for the
      multiplicity of experiences observed in the country are identified and the
      challenges facing progress toward a decentralized and regionalized health system
      in Brazil are discussed.

PMID- 22872354
TI  - [Anxiety regarding dental treatment: prevalence and predictors among Brazilians].
AB  - Considering the negative impact anxiety can exert over dental treatment, the
      scope of this study was to determine the prevalence of predictors of anxiety
      regarding dental treatment among Brazilians. A cross-sectional study was carried
      out using the Corah dental anxiety scale to assess the degree of anxiety
      regarding dental treatment among 3000 patients. The results reveal that two out
      of every eight Brazilian patients manifest moderate to severe anxiety regarding
      dental treatment. In this sample, the degree of anxiety was higher among females
      (p=0.007), over 20 years of age (p=0.006), without access to the Internet and/or
      newspapers (p=0.016), with a low frequency of oral hygiene (p=0.001), for whom
      the reason for the dental appointment was curative treatment, pain or another
      problem rather than a check up (p=0.047) and those suffering from toothache
      (p<0.001). Fear and anxiety regarding dental treatment indeed exist in the
      Brazilian population and the findings of this study suggest that, besides the
      lack of economic resources, negligence with respect to oral health, gender and
      age may increase the degree of anxiety.

PMID- 22872358
TI  - Association of childhood adversities with the first onset of mental disorders in
      Spain: results from the ESEMeD project.
AB  - PURPOSE: Childhood adversities (CAs) have consistently been associated with
      mental health problems in childhood and adulthood. However, few studies have
      employed appropriate statistical methods that take into account overlap among
      CAs, and many of the ones that did so were based on insufficiently complex
      models. The present paper studies the prevalence of a wide variety of CAs, as
      well as their relationship to the onset of mental disorders in a representative
      sample of a Spanish population. METHODS: The study is part of the ESEMeD-Spain
      project, a cross-sectional household survey, which included a nationally
      representative sample of the Spanish adult population. CAs' associations with
      lifetime prevalence of mental disorders were estimated using discrete-time
      survival analysis with person-years as the unit of analysis. RESULTS: Of our
      sample, 20.6% reported at least one CA, of whom 24% reported more than one CA.
      Parental death, parental mental disorder, family violence, economic adversity,
      physical and sexual abuse were associated with different groups of mental
      disorders. CAs were associated with the onset of mental disorders during several
      stages of life. Simulations suggest that CAs were associated with 12.6% of all
      disorders, 10.8% of mood disorders, 5.8% of anxiety disorders, 27% of substance
      disorders and 29.7% of externalising disorders. CONCLUSIONS: Prevalences of CAs
      in the Spanish population are lower than those found in other high-income
      countries, especially when compared to the USA. In Spain, different CAs were
      associated with the onset of a number of mental disorders, although these
      associations were not as frequent as in other countries. Although lower than in
      other countries, the association between CAs and mental health in Spain should be
      considered relevant. Specific health policies and prevention programmes are
      needed in order to decrease this burden.

PMID- 22872359
TI  - Resilience, lifestyle and symptoms of anxiety and depression in adolescence: the
      Young-HUNT study.
AB  - PURPOSE: This study investigated the symptoms of anxiety and depression in
      adolescence, their associations with lifestyle and resilience and the possibility
      that resilience factors can attenuate the associations between unhealthy
      lifestyle and symptoms of anxiety and depression. METHODS: Adolescents (n =
      7,639) aged 13-18 years completed a questionnaire regarding lifestyle and health.
      Symptoms of anxiety and depression were measured by the SCL-5, a five-item
      shortened version of the Hopkins Symptom Checklist. Resilience factors included
      questions on friends and family relations and two sub-scales of the Resilience
      Scale for Adolescents; Family cohesion and Social competence. RESULTS: Of the
      total population, 13% reported symptoms of anxiety and depression. Resilience
      characteristics were associated with lower symptom levels (ORs ranging from 0.2
      to 0.6), and substance use and infrequent physical activity with higher symptom
      levels (ORs ranging from 2.1 to 4.0). The associations with substance use were
      strengthened by social competence, but attenuated by family cohesion. The
      association with physical activity was attenuated by both social competence and
      family cohesion. CONCLUSION: Symptoms of anxiety and depression were frequent in
      adolescents and were associated with unhealthy lifestyle factors as substance use
      and low physical activity. Resilience characteristics seemed to protect against
      symptoms and markedly influenced the associations between lifestyle factors and
      symptoms of anxiety and depression. The importance of family and other supportive
      relationships should be emphasized in treatment and prevention of anxiety and
      depression in adolescence.

PMID- 22872360
TI  - The possible reconstruction of a sharp injury to a skull.

PMID- 22872361
TI  - Emergency medicine techniques and the forensic autopsy.
AB  - Emergency medicine measures often have to be carried out under suboptimal
      conditions in emergency situations and require invasive patient treatment. In the
      case of a fatal outcome these measures have to be evaluated at autopsy, regarding
      indications, correct implementation and possible complications. As well,
      alongside the more familiar procedures--such as endotracheal intubation,
      insertion of chest drains, external cardiac massage and cannulation of central
      and peripheral veins--there are alternative techniques being increasingly
      applied, that include new tools for the management of hemorrhagic shock, drug
      delivery and alternative airway management devices. On the one hand, all of these
      measures are essential for the survival and appropriate treatment of the injured
      and/or sick patient, but on the other hand they can damage the patient and thus
      contain a significant risk of both medical and forensic relevance for the patient
      and the physician. In the following review we provide an overview of established,
      new and alternative techniques for emergency airway management, administration of
      drugs and management of hemorrhagic shock. The aim is to facilitate the
      understanding and autopsy evaluation of current emergency medicine techniques.

PMID- 22872362
TI  - Palliation of dyspnea in pediatrics.
AB  - Dyspnea is a complex physiologic and psychosocial symptom that is difficult to
      characterize and measure, but essential to treat, as it has a significant effect
      on quality of life. Although palliation of dyspnea in the child with chronic
      illness is an under-researched area, children and their families cannot wait for
      the research to catch up with their current needs. This article addresses several
      aspects of dyspnea in pediatrics palliative care, with an eye toward practical
      suggestions for evaluation and management.

PMID- 22872363
TI  - Histopathological assessment in glossectomy: harmonic shears versus monopolar
      electrosurgery pilot study.
AB  - OBJECTIVES: The aim of the study was to gather information on outcomes and effect
      sizes of 2 surgical methods of glossectomy by using a grade system and an
      objective measure of artifacts in micrometers (um). The collected data would be
      used to plan a definitive study. STUDY DESIGN: Pilot study. SETTING: Tertiary
      referral center. MATERIAL AND METHODS: Nineteen patients affected with tongue
      cancer were consecutively enrolled in a pilot study and treated by partial
      glossectomy. Eleven patients (57.89%) of group A were treated with monopolar
      electrocautery, while 8 patients (42.10%) of group B were treated with Harmonic
      Focus Curved Shears. Specimens were examined by a pathologist blinded to the
      surgical procedure, using a 4-grade system for margin artifact assessment (margin
      fragmentation, cautery/crush artifact, extravascular blood clot, capillary
      congestion) and for measuring artifact depth. RESULTS: Artifact depth was more
      relevant in group A (765,633 um) than in group B (473,939 um). The difference
      between groups was significant at the 95% confidence interval (P < .0001). Margin
      fragmentation and capillary congestion compared between the 2 groups were of no
      significance. There were less cautery/crush artifacts and extravascular blood
      clots observed in the harmonic shears group. CONCLUSION: When used to perform a
      partial glossectomy, Harmonic Focus Curved Shears produce less cautery/crush
      artifact and a smaller artifact depth compared with monopolar cautery.

PMID- 22872364
TI  - Efficacy of per oral access in the surgical management of T2/T3 oral cavity
      squamous cell carcinoma.
AB  - OBJECTIVE: Transcutaneous "access" procedures still continue to be widely
      employed for surgical management of medium-sized (T2, T3) oral cavity tumors in
      spite of the almost 4-cm mouth opening available to the surgeon to access the
      oral cavity. We undertook a retrospective study to objectively evaluate "per oral
      access" in managing these tumors with regard to the ability to achieve a clear
      surgical margin and enable reconstruction of resultant defect. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary academic hospital. SUBJECTS AND
      METHODS: Seventy-nine consecutive patients of oral squamous cell carcinoma
      excised by per oral approach were analyzed. Multiple patient- and tumor-related
      factors known to influence status of surgical margins were analyzed. The overall
      frequency of clear, close, and involved margins was noted, as well as 5-year
      local control rate. The method of reconstruction employed was evaluated. RESULTS:
      The close/involved margins were more frequent with larger tumors and tumors
      exhibiting perineural infiltration, but none were statistically significant (P >
      .12). The overall frequency of clear, close, and involved margins was 81%, 11%,
      and 8%, respectively. Tongue and buccal mucosa sites constituted approximately
      85% of the cases and had an 85% clear margin rate. Five-year local control rate
      was 70.35%. Fifty-three free flaps reconstruction were undertaken without any
      additional "access" procedure. CONCLUSION: Our results demonstrate ability to
      obtain comparable tumor clearance rates employing per oral access, without
      compromising ability to perform optimal reconstruction. We suggest per oral
      access should be the access of choice for medium-sized oral cavity tumors, and
      additional access procedures should only be considered if the initial access
      proves inadequate.

PMID- 22872365
TI  - Characteristics and trends in ambulatory otolaryngology visits and practices.
AB  - OBJECTIVE: To determine characteristics and trends for outpatient otolaryngology
      visits and practices in the United States. STUDY DESIGN: Cross-sectional analysis
      of national survey database. SETTING: Ambulatory care settings in the United
      States. METHODS: Outpatient otolaryngology records from 2005 to 2009 were
      extracted from the National Ambulatory Medical Care Survey. Visit characteristics
      were assessed for patient type (established versus new), expected source of
      payment, and average time spent with the physician. Provider characteristic
      variables were assessed for practice type (solo versus group), employment status
      of the physician, electronic claims submission, and the use of electronic medical
      records in the practice. Trends were analyzed for the above and the average
      number of outpatient visits per otolaryngologist per year. RESULTS: A total of
      98.8 +/- 7.0 million outpatient otolaryngology office visits, consisting of 27.9
      +/- 2.1 million new patient visits and 70.9 +/- 5.3 million established patient
      visits, were studied. Expected sources of payment consisted of private insurance
      (65.1%), Medicare (21.1%), Medicaid (9.2%), and self-pay (2.0%). These sources
      did not change over the 5 calendar years (P = .301). Practitioners consisted of
      solo (30.7%) and group (69.3%) practices. Electronic medical records were in use
      in 40.2%. Electronic medical record penetration did significantly increase over
      the 5 years to 57.7% in 2009 (P = .002). The number of outpatient visits per
      otolaryngologist per year remained remarkably consistent over the years at about
      a mean of 3325 +/- 299 visits seen per year (P = .580). CONCLUSION:
      Characteristics of otolaryngology outpatient visits have remained largely
      consistent over the past 5 years. Electronic medical record penetration has
      noticeably increased. These results help validate prior Academy socioeconomic
      surveys.

PMID- 22872366
TI  - Effect of including historical height and radius BMD measurement on sarco
      osteoporosis prevalence.
AB  - BACKGROUND: A clinical need exists to improve identification of those who will
      sustain fragility fractures. Individuals with both osteoporosis (OP) and
      sarcopenia (SP), so-called "sarco-osteoporosis" (SOP), might be at higher
      fracture risk than those with OP or SP alone. Approaches to facilitate SOP
      identification, e.g., use of tallest historical rather than current height and
      inclusion of radius bone mineral density (BMD) measurement, may be of benefit.
      This study examined the effect of advancing age on SOP prevalence with and
      without use of historical tallest height and radius BMD measurement. METHODS:
      Adults age 60+ underwent dual-energy X-ray absorptiometry (DXA) BMD and total
      body composition measurement. OP and SP were defined using standard criteria: T
      score <=-2.5 at the lumbar spine or hip and appendicular lean mass (ALM)/current
      height(2) <5.45 kg/m(2) (female) and <7.26 kg/m(2) (male). Proposed "sensitive"
      SP criteria used historical tallest height instead of current height, while
      "sensitive" OP criteria added the 1/3(rd) radius T-score. The primary outcome was
      SOP prevalence by decade (60-69, 70-79, 80+). RESULTS: A total of 304 individuals
      (146 M/158 F) participated. OP, SP and SOP prevalence were higher in older adults
      and increased (p < 0.05) with the "sensitive" criteria. SOP prevalence was lower
      than that of OP or SP and increased (standard/sensitive) criteria from 1.1 % /
      4.5 % in the 60-69 years age group to 10.4 % / 21.9 % in the 80+ years age group.
      CONCLUSIONS: SOP prevalence is higher in older adults. Use of historical tallest
      height and 1/3(rd) radius BMD increases SOP prevalence. Future studies need to
      assess whether having SOP increases fracture risk and whether use of tallest
      height and/or one-third radius BMD improves fracture risk prediction.

PMID- 22872367
TI  - On the use of ultracentrifugal devices for sedimented solute NMR.
AB  - We have recently proposed sedimented solute NMR (SedNMR) as a solid-state method
      to access biomolecules without the need of crystallization or other sample
      manipulation. The drawback of SedNMR is that samples are intrinsically diluted
      and this is detrimental for the signal intensity. Ultracentrifugal devices can be
      used to increase the amount of sample inside the rotor, overcoming the intrinsic
      sensitivity limitation of the method. We designed two different devices and we
      here report the directions for using such devices and the relevant equations for
      determining the parameters for sedimentation.

PMID- 22872368
TI  - Influence of end-expiratory level and tidal volume on gravitational ventilation
      distribution during tidal breathing in healthy adults.
AB  - Our understanding of regional filling of the lung and regional ventilation
      distribution is based on studies using stepwise inhalation of radiolabelled
      tracer gases, magnetic resonance imaging and positron emission tomography. We
      aimed to investigate whether these differences in ventilation distribution at
      different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true
      during tidal breathing. Electrical impedance tomography (EIT) measurements were
      performed in ten healthy adults in the right lateral position. Five different
      EELs with four different V (T)s at each EEL were tested in random order,
      resulting in 19 combinations. There were no measurements for the combination of
      the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback
      based on airflow. The fraction of ventilation directed to different slices of the
      lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice
      versus the total lung were analysed. With increasing EEL but normal tidal volume,
      ventilation was preferentially distributed to the dependent lung and the filling
      of the right and left lung was more homogeneous. With increasing V (T) and
      maintained normal EEL (FRC), ventilation was preferentially distributed to the
      dependent lung and regional filling became more inhomogeneous (p < 0.05). We
      could demonstrate that regional and temporal ventilation distribution during
      tidal breathing was highly influenced by EEL and V (T).

PMID- 22872369
TI  - Actinopolyspora algeriensis sp. nov., a novel halophilic actinomycete isolated
      from a Saharan soil.
AB  - A halophilic actinomycete strain designated H19(T), was isolated from a Saharan
      soil in the Bamendil region (Ouargla province, South Algeria) and was
      characterized taxonomically by using a polyphasic approach. The morphological and
      chemotaxonomic characteristics of the strain were consistent with those of
      members of the genus Actinopolyspora, and 16S rRNA gene sequence analysis
      confirmed that strain H19(T) was a novel species of the genus Actinopolyspora.
      DNA-DNA hybridization value between strain H19(T) and the nearest Actinopolyspora
      species, A. halophila, was clearly below the 70 % threshold. The genotypic and
      phenotypic data showed that the organism represents a novel species of the genus
      Actinopolyspora for which the name Actinopolyspora algeriensis sp. nov. is
      proposed, with the type strain H19(T) (= DSM 45476(T) = CCUG 62415(T)).

PMID- 22872370
TI  - Hsps are up-regulated in melanoma tissue and correlate with patient clinical
      parameters.
AB  - Heat shock proteins (hsps) have been studied in numerous cancer types, but a
      clear view of their clinical relevance in melanoma remains elusive. Therefore,
      the aim of this study was to investigate the expression of hsps in melanoma with
      respect to patient clinical parameters. Using Western immunoblotting, hsps 90,
      70, 60, 40 and 32 were observed to be widely expressed in metastatic melanomas (n
      = 31), while immunofluorescence demonstrated that in the majority of samples
      these hsps, apart from hsp32, were increased in expression in melanoma cells
      compared with surrounding non-melanoma cells in situ (n = 8). Correlating hsp
      expression with patient clinical parameters indicated that greater hsp90 (P <
      0.02) and hsp40 (P < 0.03) expression correlated with advanced stage (stage III
      Vs stage IV), while in the case of hsp40, this was additionally associated with
      reduced patient survival (P < 0.05). In contrast, higher hsp32 expression was
      associated with improved patient survival (P < 0.007). On the other hand, the
      expression of the other hsps did not correlate with any obtainable patient
      clinical parameters. This study provides further evidence for the importance of
      hsps in melanoma and for their use as therapeutic targets and biomarkers, but
      larger-scale follow-up studies are required to confirm these results.

PMID- 22872371
TI  - Molecular imaging in atherosclerosis: FDG PET.
AB  - 18F-FDG PET is a new noninvasive tool for inflammation functional imaging. Low
      spatial resolution is now compensated by coregistration with CT or MRI. New
      mechanistic insights have emerged from animal and histology to explain the
      obtained signals by hypoxia, macrophage infiltration, and differentiation. Mixed
      results have been found in biomarkers studies. Interesting data have come
      recently linking plaque anatomy and function in carotids and in aortic aneurysms
      as well as inflammation and events. In coronary arteries, plaque assessment is
      still hampered by myocardium uptake but developments are being made. 18-FDG PET
      has been able to monitor inflammation before and after several therapies in
      animals and humans but to date the lack of standardization and the absence of
      prospective event-driven studies prevent this promising technique to be used in
      clinical practice.

PMID- 22872373
TI  - (Retro)sternal chest pain?
AB  - A 58-year-old man with a significant medical history notable for a coronary
      artery bypass graft (CABG) in 2001 presented at our emergency ward with
      retrosternal chest pain caused by a dehiscence of the sternal wires post CABG. 

PMID- 22872374
TI  - Erratum to: Kurt Hellmann D.M., D.Phil. Oxon. A happy 90th birthday!

PMID- 22872372
TI  - Cardiovascular benefits of dietary fiber.
AB  - The relationship between dietary fiber and risk of cardiovascular disease (CVD)
      has been extensively studied. There is considerable epidemiological evidence
      indicating an inverse association between dietary fiber intake and CVD risk. The
      association has been found to be stronger for cereal fiber than for fruit or
      vegetable fiber, and several studies have also found increased whole grain
      consumption to be associated with CVD risk reduction. In light of this evidence,
      recent US dietary guidelines have endorsed increased consumption of fiber rich
      whole grains. Regular consumption of dietary fiber, particularly fiber from
      cereal sources, may improve CVD health through multiple mechanisms including
      lipid reduction, body weight regulation, improved glucose metabolism, blood
      pressure control, and reduction of chronic inflammation. Future research should
      focus on various food sources of fiber, including different types of whole
      grains, legumes, fruits, vegetables, and nuts, as well as resistant starch in
      relation to CVD risk and weight control; explore the biological mechanisms
      underlying the cardioprotective effect of fiber-rich diets; and study different
      ethnic groups and populations with varying sources of dietary fiber.

PMID- 22872375
TI  - Cadmium and lead levels along the estuarine ecosystem of Tigre River-San Andres
      Lagoon, Tamaulipas, Mexico.
AB  - Cadmium and lead levels were evaluated in water and sediment along the estuarine
      ecosystem of Tigre River-San Andres Lagoon (Gulf of Mexico) during September to
      December 2009. Significant highest metal concentration in water (0.45 mg L(-1) Cd
      and 3.94 mg L(-1) Pb) and sediment (2.83 mg kg(-1) Cd and 6.61 mg kg(-1) Pb) were
      found at the mouth of the Tigre River, where the fishing town of El Moron is
      located. Cadmium levels in sediment were above limits associated with adverse
      biological effects on aquatic fauna, so negative impacts on natural populations
      of aquatic organisms would be expected to occur. This in turn could affect the
      fishery resources inhabiting this ecosystem.

PMID- 22872376
TI  - Residue dynamics of spirotetramat and imidacloprid in/on mango and soil.
AB  - Spirotetramat is a unique insecticide having both phloem and xylem mobility and
      imidacloprid, a neonicotinoid insecticide, is one of the most widely used in the
      world. The combination formulation is very effective against sucking pests of
      mango. Residue dynamics of spirotetramat and imidacloprid in/on mango and soil
      was studied following application of the combination formulation, spirotetramat
      12% + imidacloprid 12% (240 SC) at 90 and 180 g a.i. ha(-1). Spirotetramat
      residues in/on mango fruits were 0.327 and 0.483 mg kg(-1) after giving 3
      applications at 90 and 180 g a.i. ha(-1), respectively. The residues remained on
      mango fruits for 7 days and dissipated with the half-life of 3.3 and 5.2 days,
      respectively. Residues of spirotetramat-enol, the major metabolite of
      spirotetramat in plant, were not detected in mango fruits. Initial residues of
      imidacloprid on mango fruits from the two treatments were 0.329 and 0.536 mg kg(
      1), respectively. Imidacloprid residues remained on mango fruits beyond 15 days
      and dissipated with the half-life of 5.2 and 8.2 days. The residues of
      spirotetramat, spirotetramat-enol and imidacloprid were found below quantifiable
      limit of 0.05 mg kg(-1) in mature mango fruits and field soil at harvest.

PMID- 22872377
TI  - Comparison of greenhouse and field degradation behaviour of isoprocarb,
      hexaflumuron and difenoconazole in Perilla frutescens.
AB  - Isoprocarb, hexaflumuron and difenoconazole were used in Perilla frutescens at
      600, 60 and 75 g a.i./ha respectively. High performance liquid chromatography
      tandem mass spectrometry was used for residue determination because of high
      selectivity and simple treatment. The results showed that the half-lives of
      isoprocarb, hexaflumuron and difenoconazole at greenhouse condition were 0.71,
      1.63 and 1.21 days respectively, and at field condition, the values were 1.13,
      1.07 and 0.92 days respectively.

PMID- 22872378
TI  - Evaluation of the sensitivity of freshwater organisms used in toxicity tests of
      wastewater from explosives company.
AB  - Explosives industries are a source of toxic discharge. The aim of this study was
      to compare organisms sensitivity (Daphnia similis, Danio rerio, Escherichia coli
      and Pseudomonas putida) in detecting acute toxicity in wastewater from two
      explosives, 2,4,6-TNT (TNT) and nitrocellulose. The samples were collected from
      an explosives company in the Paraiba Valley, Sao Paulo, Brazil. The effluents
      from TNT and nitrocellulose production were very toxic for tested organisms.
      Statistical tests indicated that D. similis and D. rerio were the most sensitive
      organisms for toxicity detection in effluents from 2,4,6-TNT and nitrocellulose
      production. The P. putida bacteria was the organism considered the least
      sensitive in indicating toxicity in effluents from nitrocellulose.

PMID- 22872379
TI  - Transtemporal ultrasound application potentially elevates brain temperature:
      results of an anthropomorphic skull model.
AB  - PURPOSE: Transtemporal sonothrombolysis is a tool for a more effective treatment
      in acute stroke patients. However, some reports revealed side effects, which
      might be potentially connected to temperature elevation. To gain better insight
      into cerebral temperature changes during transtemporal sonication, diagnostic and
      therapeutic ultrasound (US) applications were evaluated using an anthropomorphic
      skull model. MATERIALS AND METHODS: The impact of diagnostic (PW-Doppler, 1.8
      MHz, 0.11 W/cm2, TIC 1.2) and therapeutic (1-MHz and 3-MHz, 0.07 - 0.71 W/cm2,
      continuous and pulsed mode) US application on temperature changes was evaluated
      at the level of muscle/temporal bone (TB), TB/brain, brain and at the middle
      cerebral artery (MCA) using 4 miniature thermocouples along the US beam.
      Sonication lasted 120 minutes. RESULTS: Diagnostic ultrasound revealed a maximum
      temperature increase of 1.45 degrees /0.60 degrees /0.39 degrees /0.41 degrees C
      (muscle/TB, TB/brain, brain, MCA) after 120 minutes. Therapeutic-1-MHz ultrasound
      raised temperature by 4.33 degrees /2.02 degrees /1.05  degrees C/0.81 degrees C
      (pulsed 1:20) and by 10.38 degrees /4.95 degrees /2.43 degrees /2.08 degrees C
      (pulsed 1:5) over 120 minutes. Therapeutic-3-MHz US raised temperature by 4.89
      degrees /2.56 degrees /1.24/1.25 degrees C (pulsed 1:20) and by 14.77 degrees
      /6.59 degrees /3.56 degrees /2.86 degrees C (pulsed 1:5) over 120 minutes,
      respectively. Continuous application of therapeutic US (1-MHz and 3-MHz) led to a
      temperature increase of 13.86 degrees /3.63 degrees /1.66 degrees /1.48 degrees C
      and 17.09 degrees /4.28 degrees /1.38/0.99 degrees C within 3 minutes.
      CONCLUSION: Diagnostic PW-Doppler showed only a moderate temperature increase and
      can be considered as safe. Therapeutic sonication is very powerful in delivering
      energy so that even pulsed application modes resulted in significant and
      potentially harmful temperature increases.

PMID- 22872380
TI  - The Use of Contrast-enhanced Ultrasound (CEUS) in Chronic Periaortitis.

PMID- 22872381
TI  - Middle cerebral artery stenosis: transcranial color-coded sonography based on
      continuity equation versus CT-angiography.
AB  - PURPOSE: Transcranial color-coded sonography (TCCS) and CT-angiography (CTA) are
      reliable tools for detection of intracranial stenosis. Current ultrasonographic
      criteria for middle cerebral artery (MCA) stenosis are usually limited to a
      dichotomized grading (< or >= 50 %). As for carotid arteries, continuity equation
      might provide a more accurate evaluation of degree of MCA stenosis. We aimed to
      apply continuity equation to calculate degree of MCA stenosis with TCCS and to
      compare these results with CTA. MATERIALS AND METHODS: All patients admitted to
      our Neurovascular Center with ischemic stroke or TIA underwent TCCS examination.
      Degree of MCA stenosis was calculated based on continuity equation as (1 -
      [PSVprestenotic/PSVintrastenotic] * 100) %. CTA was performed when TCCS detected
      MCA stenosis, and degree of stenosis was calculated by diameter (D) as: (1 -
      [Dprestenotic/Dintrastenotic] * 100) %. Correlation between TCCS and CTA results
      was tested. Continuity equation method was compared to cut-off velocity method
      for detection of >= 50 % MCA stenosis. To assess TCCS inter-observer agreement,
      evaluation of MCA stenosis was repeated by another neurosonographer in a subgroup
      of patients. RESULTS: The overall correlation coefficient between TCCS and CTA
      was 0.85 (p < 0.0001). Correlation coefficient for stenosis defined with CTA as
      >= 50 % was 0.94 (p < 0.0001). TCCS inter-observer agreement on degree of
      stenosis was 0.85 (p = 0.001). In detection of >= 50 % MCA stenosis, continuity
      equation method showed a sensitivity of 78 % (14/18) and a specificity of 86 %
      (19/22), while the cut-off velocity method showed a sensitivity of 67 % (12/18)
      and a specificity of 86 % (19/22). CONCLUSION: This study shows that
      ultrasonographic evaluation of MCA stenosis applying the continuity equation
      provides reproducible and accurate results, and is more sensitive in detection of
      >= 50 % MCA stenosis than cut-off velocity method.

PMID- 22872382
TI  - [Technical quality assurance in diagnostic ultrasound in outpatient care in
      Germany].
AB  - PURPOSE: Technical quality assurance in diagnostic ultrasound is based on
      nationally standardized protocols which are mandatory for outpatient care in
      Germany. Quality assurance includes technical requirements for sonographic
      instruments based on limiting values for technical parameters and requirements
      for image quality and documentation. Certification by regional Associations of
      Statutory Health Insurance Physicians (Kassenarztliche Vereinigungen - KV)
      requires acceptance tests to prove compliance with all required standards.
      MATERIALS AND METHODS: Between April 2009 und December 2011a total of 7457
      acceptance tests were performed by the KV Westfalen-Lippe, which represents
      nearly 13 000 physicians in northwestern parts of Germany. Results of these
      acceptance tests are evaluated with respect to display mode or Doppler technique,
      anatomic region and year of manufacture of the instruments. RESULTS: In 2469
      acceptance tests (33 %), objections were raised, mainly due to noncompliance with
      technical parameters. The frequency of objections strongly increases with the age
      of sonographic instruments and exceeds 90 % for instruments manufactured before
      1995. In acceptance tests where compliance with technical parameters has been
      approved, insufficient documentation was reported in 6 % and inadequate image
      quality in 8 % of the tests. Frequency and cause of objections depend on display
      mode and anatomic region. CONCLUSION: The study shows that sonographic
      instruments of higher age often do not meet the required standards, and it can be
      expected that updates in technical equipment will result in improvements in
      diagnostic performance and clinical outcome.

PMID- 22872384
TI  - Editor's note. The Rio+20 Summit.

PMID- 22872383
TI  - [Closing gastroschisis: a distinct entity with high morbidity and mortality].
AB  - PURPOSE: We correlate severe bowel damage in gastroschisis to the rare
      intrauterine event of narrowing of the abdominal wall around the protruding
      intestines. We describe this "closing gastroschisis" as a distinct entity.
      Prenatal ultrasound findings as gastric or bowel dilation were compared to the
      postnatal findings in order to find markers for an early in utero diagnosis of
      closing gastroschisis. Early diagnosis could prompt timely delivery to save the
      compromised bowel and avoid short gut syndrome. MATERIALS AND METHODS: We
      documented the pre- and postnatal course of our patients with gastroschisis from
      2007 to 2009.  Closing gastroschisis was suspected antenatally and confirmed
      postnatally. We identified 5 out of 18 patients showing closure of the abdominal
      wall with varying degrees of bowel damage. Prenatal ultrasound findings were
      correlated to the postnatally confirmed extent of intestinal damage. RESULTS: We
      could not find consistent ultrasound markers for prenatal diagnosis of closing
      gastroschisis. In prenatal ultrasound three patients presented significant
      gastric dilation and then experienced severe courses postnatally due to segmental
      gut necrosis. One of these three died and the other two developed short gut
      syndrome. In one case progressive intraabdominal loop dilation with simultaneous
      shrinking of the extraabdominal loops occurred corresponding to closing
      gastroschisis with segmental midgut necrosis. CONCLUSION: Closing gastroschisis
      must be seen as a special form of gastroschisis. Extended intestinal damage is
      often life-threatening. In longitudinal observation dynamics of fetal ultrasound
      findings can lead to the diagnosis of closing gastroschisis. Progressive
      intraabdominal loop dilation is always highly suspicious and must lead to close
      follow-up and timely delivery.

PMID- 22872385
TI  - 'Hot' Earth in the mass media: the reliability of news reports on global warming.
AB  - Research into the reliability of news reports on 'global warming' published by
      the UOL media group, Folha.com and Folha de S. Paulo reveals a tendency for
      positions to be polarized between complete agreement with the assertion that the
      causes are entirely anthropogenic (the dominant position) and complete denial.
      The sample comprised 676 news items from more than 3,000 published on the topic
      between October 2007 and October 2008. The study tested the hypothesis that the
      news output of the three media outlets is dominated by the positions of the
      Intergovernmental Panel on Climate Change. In absolute terms, the panel is the
      most frequently cited source, since just seven news items comprised exceptions to
      the 'consensus.' These contrary opinions made up 1.03% of the sample.

PMID- 22872386
TI  - Scientific research and Portuguese colonial policy: developments and
      articulations, 1936-1974.
AB  - The development of a colonial scientific policy by the Portuguese state in the
      twentieth century is investigated by studying the Junta de Investigacoes do
      Ultramar. Directly subordinated to the Ministerio das Colonias/do Ultramar and
      based in Lisbon, this entity's main attribute was to coordinate the scientific
      studies to be undertaken in colonial territories under Portuguese rule. The aim
      is to identify the institution's origins and objectives, to understand how its
      activities tied in with colonial policies, to detect what impacts the
      international scenario had on its trajectory and its strategic options. Special
      attention is given to the period that started after the Second World War, which
      was aligned with the mirage of development and reacted against the progress of
      the anti-colonial movement.

PMID- 22872387
TI  - Between parasitic theory and experimental oncology: a proposal for systematizing
      oncological science in Portugal, 1889-1945.
AB  - This article deals with the bio-medical investigation of cancer studies in
      Portugal between 1889 and 1945. By examining the main works produced between the
      end of the nineteenth century and the middle of the twentieth century, it has
      been possible to illuminate and define a field of scientific endeavour which has
      been the scope of little study to date. Starting from the introduction and
      consolidation of the defining principles of experimental oncology, distinct
      phases can be discerned in the production of scientific material, alternating
      between support for the dominant theories and the application of methods for
      artificially creating the disease. In accordance with the principal phases of
      investigation, a brief systematic overview of the scope of these oncological
      studies is presented.

PMID- 22872388
TI  - [Egas Moniz (1874-1955): culture and science].
AB  - On the occasion of the sixtieth anniversary of the award in 1949, the Nobel Prize
      in Physiology or Medicine granted to Egas Moniz and Walter Rudolf Hess, the
      circumstances that explain the unique Nobel award require elucidation. Attention
      is drawn to the biographical traits of Egas Moniz, which are also those of many
      doctors of his generation, as well as the details which relate to the process of
      nomination and scientific appraisal to be eligible for the Nobel Prize. Aspects
      of the link between culture and science are also discussed, including the
      controversies surrounding the award conferred upon him.

PMID- 22872389
TI  - The lives of children and their public intimacy: social work as a new factor in
      attending to the needs of children in Latin America, 1928-1948.
AB  - The professionalization of attention to the needs of children, which has taken
      place during the course of the twentieth century in areas such as health,
      education, law and social assistance, underwent an important conceptual
      development in the first decades of the twentieth century. In the field of social
      assistance, the structuring of the area of social services marked the
      introduction of a new variable in formulating policies and practices towards
      children. This article examines how the subject of social services was discussed,
      in the context of the American continent, at the Pan American Child Congresses
      which took place between 1928 and 1948, when its development was proposed as a
      new tool for social policies, especially for those directed towards children.

PMID- 22872390
TI  - [The portrayal of malaria in the works of Joao Guimaraes Rosa].
AB  - The article discusses the historical, scientific and literary aspects of malaria,
      with an emphasis on images of the disease in the work of the writer Joao
      Guimaraes Rosa. The main reference for this study is the short story "Sarapalha,"
      which is featured in the book entitled Sagarana. The author's medical training
      together with his experiences in the hinterlands of the country is the subject
      matter for the work, with stories of the harsh reality of life in the outback. A
      highlight of the story is the narrative of malaria in the language of the
      outback, though with absolute medical and scientific precision.

PMID- 22872391
TI  - [The Centro Espirita Redemptor and the treatment of mental illness, 1910-1921].
AB  - Spiritism is a religious doctrine originated in France during the nineteenth
      century through the works of Allan Kardec. In Brazil, it assumed an original
      configuration: rational and scientific Christian spiritism, pioneered by Luiz de
      Mattos, was one of the national doctrinal variants. Luiz de Mattos created the
      Centro Espirita Redemptor where, for some years, he monitored the treatment of
      the mentally ill. The article analyzes the characteristics of rational and
      scientific Christian spiritism treatment applied to mental illness and the
      strategies that Luiz de Mattos adopted to defend his form of treatment. Some
      similarities and differences between spiritist and medical treatment are also
      outlined.

PMID- 22872392
TI  - [The epistemic objects of toxoplasmoses and their re-presentation in an
      international scientific conference].
AB  - The paper investigates the epistemic objects of Toxoplasma gondii and the
      correlation of forces of research groups committed to redefine or reconfigure
      toxoplasmosis. The data research and this analysis were conducted in a scientific
      congress, according to the concepts of 'manipulation' and 'reenactment,' based on
      the idea of 'dramatization' proposed by Mol in a study of empirical philosophy.
      It was found that the objects were represented from diversified hues and with
      strong ties to the industrial complex. For its projection in the trends of the
      global economy in the twenty-first century, genetics was a major protagonist in
      the debates on sole causality, one of the convictions of Western science.

PMID- 22872393
TI  - [Brazil-Mozambique, links in scientific policy: an interview with Lidia Brito.
      Interview by Luisa Massarani and Luanda Lima].
AB  - This text presents an interview with Lidia Brito, director of the Division of
      Policy and Training in Science of the United Nations Educational, Scientific and
      Cultural Organization (Unesco) and former minister of the Ministry of Science,
      Technology and Innovation of Mozambique. With a discerning eye, Brito discusses
      some of the current challenges facing science in Mozambique,the importance of
      establishing partnerships between developing countries and the popularization of
      science. With her highly charismatic personality, she also discusses her
      activities in Unesco and the role of women in science.

PMID- 22872394
TI  - [Theses on hepatitis at the Faculdade de Medicina of the Universidade Federal do
      Rio de Janeiro, 1837-2000].
AB  - An inventory of the theses on hepatitis of the Faculdade de Medicina of the
      Universidade Federal do Rio de Janeiro between 1837 and 2000 is presented. The
      analysis indicates the potential and limits for discussion of the evolutionary
      framework of scientific knowledge on these health problems in Brazil. The
      theories are also discussed in light of their scientific reference points and the
      technological and social changes that influenced them. The landmarks in medical
      education and knowledge about hepatitis are identified and categorized,
      considering that the theses reveal at the very least the state of the art on the
      subject. The study makes it possible to explore the foundations upon which the
      scientific knowledge on hepatitis were built and indicate possibilities for
      research in the reconstruction of scientific knowledge of other health problems.

PMID- 22872395
TI  - [De uisu: the oldest surviving treatise on ophthalmology in the West].
AB  - We present here in Portuguese the oldest treatise that the West has bequeathed us
      about ophthalmology and eyesight in general, namely "On vision" or De uisu in
      Latin, with an introductory study that seeks to situate its place in the history
      of medicine, without, however, failing to dwell on the philological difficulties
      that the text contains.

PMID- 22872396
TI  - The dilemmas of a scientific tradition: higher education, science, and public
      health at the Instituto Oswaldo Cruz, 1908-1953.
AB  - The article analyzes the tradition in medical and scientific teaching that was
      established at the Instituto Oswaldo Cruz starting in 1908, introducing an
      innovative standard in training researchers and public health workers that
      combined teaching and research activities. Forerunner of the university model,
      this tradition came up against the question of what social role the institute
      should play in the new institutional organization of public health and education
      implemented during the Vargas era: should the Institute serve public health or
      adopt a university-like format?

PMID- 22872397
TI  - [The teaching of history at the Faculdade Nacional de Filosofia of the
      Universidade do Brasil].
AB  - This work analyzes the trajectory of the history course at the Faculdade Nacional
      de Filosofia of the Universidade do Brasil between 1939 and 1964/1965. Special
      emphasis is placed on the period between 1955 and 1965, when there was the
      separation of the history and geography courses, through to the onset of the
      reorganization of the schools and institutes of the university. The Faculdade
      Nacional de Filosofia was a benchmark for the other schools of philosophy in the
      country, as well as being a reference in the development of the history of
      education in Brazil. The approach adopted is geared to the field of the history
      of the historiography, with a focus on the study of the trajectories,
      institutions and relationship networks.

PMID- 22872398
TI  - Anisio Teixeira on universities, research and public education.
AB  - The article investigates the issues that were central to the debate about
      Brazilian education in intellectual circles in the 1920s-1930s and 1950s-1960s.
      It analyzes the project for Universidade do Distrito Federal, highlighting what
      set it apart from other higher education models, and the articulation between
      education and social science that oriented the work of Centro Brasileiro de
      Pesquisas Educacionais, founded and run by Anisio Teixeira. The positions of
      Darcy Ribeiro and Anisio Teixeira concerning the plans for Universidade de
      Brasilia are set forth. The changes in Brazil's intellectual field in the midst
      of competing university projects and the prospect of developing social science
      research and applying it to education policymaking are analyzed.

PMID- 22872399
TI  - [Scientific training and professional practice in the career of Carlos Chagas
      Filho].
AB  - The study dwells on the scientific background of Carlos Chagas Filho, between
      1926 and 1942, which was the period of socialization of the scientist in the
      Faculdade de Medicina do Rio de Janeiro and the Instituto Oswaldo Cruz. It covers
      the period from the beginning of his professional career to the moment when he
      resigned from the administration of the Servico de Estudos de Grandes Endemias in
      1942 to devote himself to his academic career at the Laboratorio de Fisica
      Biologica. The way in which his social and scientific resources were deployed
      throughout his career is analyzed, with a view to ascertaining the moment when he
      broke with the tradition of biomedical research of Manguinhos and embarked on the
      construction of a new location where he could implement his own scientific
      project.

PMID- 22872400
TI  - [Science as a profession: an interview with Carlos Chagas Filho].
AB  - The editing of this interview focuses on aspects of the extensive professional
      career of Carlos Chagas Filho, who was the founder of the Instituto de Biofisica
      of the Universidade do Brasil, currently the Universidade Federal do Rio de
      Janeiro. It highlights the scientific and political role he played in Brazilian
      science and on the international scene. His memoirs include his experience at the
      Instituto Oswaldo Cruz, where he began his scientific training; the efforts to
      create the Laboratorio de Fisica Biologica, succeeded by the Instituto de
      Biofisica; his work on the Conselho Nacional de Pesquisas and the Academia
      Brasileira de Ciencias; the part he played at the United Nations Educational,
      Scientific and Cultural Organization; his time as president of the Pontifical
      Academy of Sciences of the Vatican, which led him to ponder questions about the
      relationship between science and religion.

PMID- 22872410
TI  - Task set flexibility and feature specificity modulate the limits of temporal
      attention.
AB  - The consequences of maintaining a task set in the context of the (speeded)
      attentional blink were investigated in a series of experiments. Observers were
      asked to either attend or ignore the first of two target stimuli (T1 and T2). The
      results showed that when T1 and T2 shared a task relevant feature that was unique
      to T2, but not to T1, a shallow attentional blink was observed, as well as a lack
      of Lag 1 sparing. In comparison, when the targets shared a feature that was
      uniquely task relevant to both targets, the blink could not be avoided.
      Conversely, when no feature was shared between targets, ignoring T1 was
      successful and virtually no attentional costs were apparent. A similar lack of
      costs was also observed when targets shared a task relevant feature that was
      unique to T1 but not to T2. Finally, matching the feature dimension of a target
      feature that was unique to T2, but not T1, also strongly attenuated the blink.
      However, it did not completely abolish Lag 1 sparing. The results are interpreted
      in the context of current models of the attentional blink. 

PMID- 22872411
TI  - Dorsal versus transgluteal approach for hip hemiarthroplasty: an analysis of
      early complications in seven hundred and four consecutive cases.
AB  - PURPOSE: Hemiarthroplasty (HA) is an established treatment for femoral neck
      fractures of the elderly. Several surgical approaches are currently used
      including dorsal and transgluteal. It is still unclear whether one approach may
      be advantageous. We compared early complication rates after dorsal and
      transgluteal approaches. METHODS: We retrospectively analysed a cohort including
      704 consecutive patients who received HA for femoral neck fracture; 212 male and
      492 female patients were included, and the mean age was 80.4 years (SD 9.8
      years). In 487 patients a dorsal and in 217 a transgluteal approach was chosen.
      In all patients an Excia stem with self-centring bipolar head manufactured by
      Aesculap (Tuttlingen, Germany) was used. We evaluated early postoperative
      complications including dislocation, infection, haematoma, seroma and
      perioperative fracture. Complication rates after dorsal and transgluteal
      approaches were calculated and compared by the chi-square test. RESULTS: After a
      dorsal approach 10.5 % [confidence interval (CI) 7.7-13.2 %] of the patients
      suffered one or more early complications. Following a transgluteal approach this
      proportion was 9.7 % (CI 5.7-13.6 %), which was not significantly different (p =
      0.75). The predominant complication after a dorsal approach was dislocation (3.9
      %; CI 2.2-5.6 %). The dislocation rate after a transgluteal approach was
      significantly lower (0.5 %; CI 0-1.4 %). Postoperative haematoma however was seen
      after a transgluteal approach in 5.5 % (CI 2.5-8.6 %), which was significantly
      more frequent than after a dorsal approach (1.2 %; CI 0.2-2.2 %). The frequency
      of the other types of complications did not significantly differ. CONCLUSIONS:
      The rate of early surgical complications after dorsal and transgluteal approaches
      is not significantly different. However, the dorsal approach predisposed to
      dislocation, whereas the transgluteal approach predisposed to haematoma.

PMID- 22872412
TI  - Surgical repair of hip abductors. A new technique using Graft Jacket allograft
      acellular human dermal matrix.
AB  - PURPOSE: Avulsion of the abductors from the hip can be an infrequent but
      debilitating complication after total hip arthroplasty performed through a trans
      gluteal approach. This can result in intractable pain, limp, Trendelenberg lurch
      and instability of the hip. There have been various methods described for
      repairing or reconstruction of this abductor muscle complex including direct
      trans-osseous repair, muscle transfers, muscle and tendon sling, bone tendon
      allograft reconstruction and endoscopic repair techniques. METHODS: In a
      prospective study at our institution we evaluated the results of a surgical
      technique in 12 patients using a trans-osseous repair of gluteus medius and
      minimus insertions augmented by a Graft Jacket allograft acellular human dermal
      matrix (Graft Jacket; Wright Medical Technology, Arlington, TN) over the anterior
      and anterolateral aspects of the greater trochanter. Diagnosis of hip abductor
      avulsions was made by evaluation of the history of presenting complaint, clinical
      examination and confirmed by ultrasound or MRI scans. RESULTS: Evaluation of
      results included pain scoring, gait evaluation, Trendelenberg test, and the
      Harris hip score. There was a significant improvement in pain (VAS mean values
      8.25 to 2.33; p value < 0.0001), limp and gait along with abductor strength. The
      Trendelenberg test became negative in all but one. At the mean follow up of 22
      months Harris hip scores improved from 34.05 to 81.26 (p value <0.0001).
      CONCLUSION: Overall this procedure appears to be safe and associated with high
      patient satisfaction, without the morbidity of any tendon or muscle transfers.

PMID- 22872413
TI  - Prefactual potency: the perceived likelihood of alternatives to anticipated
      realities.
AB  - Prefactual thoughts typically take the form of implied or explicit if-then
      statements that represent mental simulations of alternatives to what is expected
      to occur in the future. The authors propose that the multiplicative combination
      of "if likelihood" (the degree to which the antecedent condition of the
      prefactual is perceived to be likely) and "then likelihood" (the perceived
      conditional likelihood of the outcome of the prefactual, given the antecedent
      condition) determine the influence of prefactuals. This construct, termed
      prefactual potency, is a reliable predictor of the degree of influence of
      prefactual thinking on judgments of anticipated negative affect. Through three
      experiments, the authors demonstrate the predictive power of this construct and
      show that it plays a causal role in determining the strength of the effects of
      prefactual thought. Implications of prefactual potency as a central factor of
      prefactual influence are discussed.

PMID- 22872414
TI  - Level-dependent changes in perception of speech envelope cues.
AB  - Level-dependent changes in temporal envelope fluctuations in speech and related
      changes in speech recognition may reveal effects of basilar-membrane
      nonlinearities. As a result of compression in the basilar-membrane response, the
      "effective" magnitude of envelope fluctuations may be reduced as speech level
      increases from lower level (more linear) to mid-level (more compressive) regions.
      With further increases to a more linear region, speech envelope fluctuations may
      become more pronounced. To assess these effects, recognition of consonants and
      key words in sentences was measured as a function of speech level for younger
      adults with normal hearing. Consonant-vowel syllables and sentences were
      spectrally degraded using "noise vocoder" processing to maximize perceptual
      effects of changes to the speech envelope. Broadband noise at a fixed signal-to
      noise ratio maintained constant audibility as speech level increased. Results
      revealed significant increases in scores and envelope-dependent feature
      transmission from 45 to 60 dB SPL and decreasing scores and feature transmission
      from 60 to 85 dB SPL. This quadratic pattern, with speech recognition maximized
      at mid levels and poorer at lower and higher levels, is consistent with a role of
      cochlear nonlinearities in perception of speech envelope cues.

PMID- 22872416
TI  - Hydrogen dissociation on diene-functionalized carbon nanotubes.
AB  - Chemical functionalization of a zigzag carbon nanotube (CNT) with 1, 3
      cyclohexadiene (CHD), previously reported by experimentalists, has been
      investigated in the present study using density functional theory in terms of
      energetic, geometric, and electronic properties. Then, the thermodynamic and
      kinetic feasibility of H2 dissociation on the pristine and functionalized CNTs
      have been compared. The dissociation energy of the H2 molecule on the pristine
      and functionalized CNT has been calculated to be about -1.00 and -1.55 eV, while
      the barrier energy is found to be about 3.70 and 3.51 eV, respectively.
      Therefore, H2 dissociation is thermodynamically more favorable on the CNT-CHD
      system than on the pristine tube, while the favorability of the dissociation on
      the pristine tube is higher in term of kinetics.

PMID- 22872417
TI  - Probing the structural and electronic properties of aluminum-sulfur AlnSm
      (2<=n+m<=6) clusters and their oxides.
AB  - Using the first-principle density functional calculations, the equilibrium
      geometries and electronic properties of anionic and neutral aluminum-sulfur AlnSm
      (2<=n+m<=6) clusters have been systematically investigated at B3PW91 level. The
      optimized results indicate that the lowest-energy structures of the anionic and
      neutral AlnSm clusters prefer the low spin multiplicities (singlet or doublet)
      except the Al2?, Al2, S2, Al4 and Al2S4 clusters. A significant odd-even
      oscillation of the highest occupied-lowest unoccupied molecular orbital (HOMO
      LUMO) energy gaps for the AlnSm? clusters is observed. Electron detachment
      energies (both vertical and adiabatic) are discussed and compared with the
      photoelectron spectra observations. Furthermore, a good agreement between
      experimental and theoretical results gives confidence in the most stable clusters
      considered in the present study and validates the chosen computational method. In
      addition, the variation trend of chemical hardness is in keeping with that of
      HOMO-LUMO energy gaps for the AlnSm clusters. Upon the interaction of oxygen with
      the stable AlSm? clusters, the dissociative chemisorptions are favorable in
      energy. The binding energy and Gibbs free energy change show completely opposite
      oscillating behaviors as the cluster size increases.

PMID- 22872415
TI  - Conformational dynamics of threonine 195 and the S1 subsite in functional trypsin
      variants.
AB  - Replacing the catalytic serine in trypsin with threonine (S195T variant) leads to
      a nearly complete loss of catalytic activity, which can be partially restored by
      eliminating the C42-C58 disulfide bond. The 0.69 MUs of combined explicit solvent
      molecular dynamics (MD) simulations revealed continuous rearrangement of T195
      with different conformational preferences between five trypsin variants tested.
      Among three conformational families observed for the T195 residue, one showed the
      T195 hydroxyl in a conformation analogous to that of the serine residue in wild
      type trypsin, positioning the hydroxyl oxygen atom for attack on the carbonyl
      carbon of the peptide substrate. MD simulations demonstrated that this
      conformation was more populated for the C42A/C58V/S195T and C42A/C58A/S195T
      triple variants than for the catalytically inactive S195T variant and correlated
      with restored enzymatic activities for triple variants. In addition, observation
      of the increased motion of the S214-G219 segment in the S195T substituted
      variants suggested an existence of open and closed conformations for the
      substrate binding pocket. The closed conformation precludes access to the S1
      binding site and could further reduce enzymatic activities for triple variants.
      Double variants with intact serine residues (C42A/C58A/S195 and C42A/C58V/S195)
      also showed interchange between closed and open conformations for the S214-G219
      segment, but to a lesser extent than the triple variants. The increased
      conformational flexibility of the S1 subsite, which was not observed for the wild
      type, correlated with reduced enzymatic activities and suggested a possible mode
      of substrate regulation for the trypsin variants tested.

PMID- 22872418
TI  - Dielectric analysis and multi-cell electrofusion of the yeast Pichia pastoris for
      electrophysiological studies.
AB  - The yeast Pichia pastoris has become the most favored eukaryotic host for
      heterologous protein expression. P. pastoris strains capable of overexpressing
      various membrane proteins are now available. Due to their small size and the
      fungal cell wall, however, P. pastoris cells are hardly suitable for direct
      electrophysiological studies. To overcome these limitations, the present study
      aimed to produce giant protoplasts of P. pastoris by means of multi-cell
      electrofusion. Using a P. pastoris strain expressing channelrhodopsin-2 (ChR2),
      we first developed an improved enzymatic method for cell wall digestion and
      preparation of wall-less protoplasts. We thoroughly analyzed the dielectric
      properties of protoplasts by means of electrorotation and dielectrophoresis.
      Based on the dielectric data of tiny parental protoplasts (2-4 MUm diameter), we
      elaborated efficient electrofusion conditions yielding consistently stable
      multinucleated protoplasts of P. pastoris with diameters of up to 35 MUm. The
      giant protoplasts were suitable for electrophysiological measurements, as proved
      by whole-cell patch clamp recordings of light-induced, ChR2-mediated currents,
      which was impossible with parental protoplasts. The approach presented here
      offers a potentially valuable technique for the functional analysis of low-signal
      channels and transporters, expressed heterologously in P. pastoris and related
      host systems.

PMID- 22872419
TI  - Investigation of optimum anti-scatter grid selection for digital radiography:
      physical imaging properties and detectability of low-contrast signals.
AB  - Our aim in this study was to evaluate the effect of the grid variations on the
      imaging performance for a computed radiographic system under identical exposure
      condition. Digital radiographies using a 20-cm Lucite phantom were performed
      without grid and with grid ratios of 5:1, 8:1, 10:1, 12:1, and 14:1. The scatter
      fraction, the incident dose to the image receptor, the Wiener spectrum (WS), and
      the noise-equivalent quanta (NEQ) were measured. Visibility of low-contrast
      signals was evaluated using a contrast-detail phantom. The scatter fractions
      decreased considerably with an increase in the grid ratio. On the other hand, the
      WSs were increased (the noise property deteriorated) as the grid ratio increased
      due to a decreased incident dose to the image receptor under the identical
      exposure condition. The NEQs were improved as the grid ratio increased. The high
      grid ratios provided higher low-contrast detectability compared to the low grid
      ratios. Our results indicated that the removal of scattered radiation was very
      effective in improvement of the NEQ in the digital system under the identical
      exposure condition.

PMID- 22872420
TI  - Usefulness of presentation of similar images in the diagnosis of breast masses on
      mammograms: comparison of observer performances in Japan and the USA.
AB  - Computer-aided diagnosis has potential in improving radiologists' diagnosis, and
      presentation of similar images as a reference may provide additional useful
      information for distinction between benign and malignant lesions. In this study,
      we evaluated the usefulness of presentation of reference images in observer
      performance studies and compared the results obtained by groups of observers
      practicing in the United States and Japan. The results showed that the
      presentation of the reference images was generally effective for both groups, as
      the areas under the receiver operating characteristic curves improved from 0.915
      to 0.924 for the group in the US and from 0.913 to 0.925 for the group in Japan,
      although the differences were marginally (p = 0.047) and not (p = 0.13)
      statistically significant, respectively. There was a slight difference between
      the two groups in the way that the observers reacted to some benign cases, which
      might be due to differences in the population of screenees and in the socio
      clinical environment. In the future, it may be worthwhile to investigate the
      development of a customized system for physicians in different socio-clinical
      environments.

PMID- 22872421
TI  - Optimal injection rate and volume of contrast medium for observing hemodynamics
      of a hepatocellular carcinoma structure model.
AB  - This study aimed to identify the optimal concentration, injection rate, and total
      volume of contrast medium (CM) for evaluating the hemodynamics of a
      hepatocellular carcinoma (HCC) structure model of diameter 35 mm, using multi
      level dynamic computed tomography (M-LDCT) with 64 detector rows. A tube was
      inserted in the model as a simulated vessel. Five CM concentrations were used:
      non-diluted, 2-, 3-, 6-, and 9-fold diluted. Five regions of interest were placed
      within the HCC structure model. Time-density curves were created for CM injection
      rates of 1, 2, and 3 ml/s for 10 s, and for a total volume of 10 ml, followed by
      saline injection at 1 ml/s. M-LDCT maximum intensity projection images were
      evaluated by four appraisers using a three-point scale (excellent, 2; good, 1;
      poor, 0). There was no significant difference between maximum CT values at 2 ml/s
      for 10 s and those at 3 ml/s; these values were both greater than those at 1
      ml/s. The duration of the peak was maintained for longer at 3 ml/s for 10 s (5.2
      +/- 2.3 s) than at 2 ml/s (3.6 +/- 0.9 s). Maximum CT values at 2 ml/s of a total
      volume of 10 ml were greater than those at 3 ml/s. The highest scores of 7 and 8
      were found at 2 and 3 ml/s for 10 s, using 2-, 3-, or 6-fold diluted CM. The most
      appropriate CM rate for evaluating hemodynamics was 2 ml/s for 10 s, using 2-, 3
      , or 6-fold diluted CM.

PMID- 22872423
TI  - Using ES cells labeled with GFP for analyzing cell behavior during
      differentiation.
AB  - Mouse embryonic stem (ES) cell is a unique yet highly successful system to study
      stem cell maintenance and differentiation. In this protocol, we describe the
      generation of engineered mouse ES cells that stably express GFP alone or GFP
      fused with histone H2B, which allow the cells to be traced live or in fixed
      samples. This system can be used to study cell behavior changes as ES cells
      differentiate into different lineages.

PMID- 22872422
TI  - Diabetes and kidney transplantation: past, present, and future.
AB  - Diabetes mellitus is the most common etiology for end stage renal disease (ESRD)
      worldwide and in the United States. The incidence of morbidity and mortality is
      higher in diabetic patients with ESRD due to increased cardiovascular events.
      Patients with type 2 diabetes who receive a renal allograft have a higher
      survival rate compared with patients who are maintained on chronic hemodialysis
      therapy, but there is scarcity of data on long-term graft outcomes. Most recently
      the development of new onset diabetes after transplantation (NODAT) poses a
      serious threat to patient and allograft survival. Pre-emptive transplantation and
      the use of living donors have improved overall survival. In addition, critical
      management of glucose, blood pressure, and cholesterol are some of the factors
      that can help minimize adverse outcomes in both patients with pre-existing
      diabetes and patients who develop NODAT. Future clinical trials are warranted to
      improve therapeutic medical management of these patients thus influencing graft
      attrition.

PMID- 22872424
TI  - Dopaminergic differentiation of human pluripotent cells.
AB  - Here we describe protocols for the dopaminergic differentiation of pluripotent
      stem cells. We have optimized and compared two distinct protocols, both of which
      are chemically defined and applicable to both embryonic and induced pluripotent
      stem cells. First, we present a five-step method based on rosette formation
      (Basic Protocol 1); then we describe a monolayer paradigm based on inhibition of
      alternate developmental pathways (Basic Protocol 2). Directed differentiation of
      pluripotent cells into specific cell types is a crucial step towards
      understanding human development and realizing the biomedical relevance of these
      cells, whether for replacement therapy or disease modeling.

PMID- 22872425
TI  - Scalable production of transplantable dopaminergic neurons from hESCs and iPSCs
      in xeno-free defined conditions.
AB  - Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are
      potentially an unlimited cell source for cell replacement therapy and
      personalized medicine. Before hESC- and iPSC-based therapy can be moved from
      bench to bedside, however, it is essential to establish protocols for generating
      therapeutically relevant cells, like dopaminergic neurons in defined conditions
      that are suitable for scalable good manufacturing practice (GMP)-compliant
      protocols. Here, the derivation and differentiation of functional dopaminergic
      neurons from hESCs and iPSCs under xeno-free defined conditions are described.
      These protocols have been validated in multiple hESC and iPSC lines.

PMID- 22872426
TI  - Isolation of undifferentiated female germline cells from adult Drosophila
      ovaries.
AB  - This unit describes a method for isolating undifferentiated, stem cell-like
      germline cells from adult Drosophila ovaries. Here, we demonstrate that this
      population of cells can be effectively purified from hand-dissected ovaries in
      considerably large quantities. Tumor ovaries with expanded populations of
      undifferentiated germline cells are first removed from fly abdomens and
      dissociated into a cell suspension with the aid of protease treatment. The target
      cells, which express Vasa-green fluorescent protein (GFP) fusion protein under
      the control of the germline-specific vasa promoter, are specifically selected
      from the suspension via fluorescence-activated cell sorting (FACS). These
      protocols can be adapted to isolate other cell types from fly ovaries, such as
      somatic follicle cells or escort cells, by driving GFP expression in the
      respective target cells.

PMID- 22872427
TI  - Randomized, double-blind trial of the effect of fluid composition on electrolyte,
      acid-base, and fluid homeostasis in patients early after subarachnoid hemorrhage.
AB  - BACKGROUND: Hyper- and hyponatremia are frequently observed in patients after
      subarachnoidal hemorrhage, and are potentially related to worse outcome. We
      hypothesized that the fluid regimen in these patients is associated with distinct
      changes in serum electrolytes, acid-base disturbances, and fluid balance.
      METHODS: Thirty-six consecutive patients with SAH were randomized double-blinded
      to either normal saline and hydroxyethyl starch dissolved in normal saline
      (Voluven((r)); saline) or balanced crystalloid and colloid solutions
      (Ringerfundin((r)) and Tetraspan((r)); balanced, n = 18, each) for 48 h.
      Laboratory samples and fluid balance were evaluated at baseline and at 24 and 48
      h. RESULTS: Age [57 +/- 13 years (mean +/- SD; saline) vs. 56 +/- 12 years
      (balanced)], SAPS II (38 +/- 16 vs. 34 +/- 17), Hunt and Hess [3 (1-4) (median,
      range) vs. 2 (1-4)], and Fischer scores [3.5 (1-4) vs. 3.5 (1-4)] were similar.
      Serum sodium, chloride, and osmolality increased in saline only (p <= 0.010, time
      group interaction). More patients in saline had Cl >108 mmol/L [16 (89 %) vs. 8
      (44 %); p = 0.006], serum osmolality >300 mosmol/L [10 (56 %) vs. 2 (11 %); p =
      0.012], a base excess <-2 [12 (67 %) vs. 2 (11 %); p = 0.001], and fluid balance
      >1,500 mL during the first 24 h [11 (61 %) vs. 5 (28 %); p = 0.046]. Hyponatremia
      and hypo-osmolality were not more frequent in the balanced group. CONCLUSIONS:
      Treatment with saline-based fluids resulted in a greater number of patients with
      hyperchloremia, hyperosmolality, and positive fluid balance >1,500 mL early after
      SAH, while administration of balanced solutions did not cause more frequent
      hyponatremia or hypo-osmolality. These results should be confirmed in larger
      studies.

PMID- 22872428
TI  - Detection of gene expression signatures related to underlying disease and
      treatment in rheumatoid arthritis patients.
AB  - OBJECTIVES: Gene expression signatures can provide an unbiased view into the
      molecular changes underlying biologically and medically interesting phenotypes.
      We therefore initiated this study to identify signatures that would be of utility
      in studying rheumatoid arthritis (RA). METHODS: We used microarray profiling of
      peripheral blood mononuclear cells (PBMCs) in 30 RA patients to assess the effect
      of different biologic agent (biologics) treatments and to quantify the degree of
      a type-I interferon (IFN) signature in these patients. A numeric score was
      derived for the quantification step and applied to patients with RA. To further
      characterize the IFN response in our cohort, we employed type-I IFN treatment of
      PBMCs in vitro and in reporter assays. RESULTS: Profiling identified a subset of
      RA patients with upregulation of type-I IFN-regulated transcripts, thereby
      corroborating previous reports showing RA to be heterogeneous for an IFN
      component. A comparison of individuals currently untreated with a biologic with
      those treated with infliximab, tocilizumab, or abatacept suggested that each
      biologic induces a specific gene signature in PBMCs. CONCLUSIONS: It is possible
      to observe signs of type-I IFN pathway activation in a subset of clinically
      active RA patients without C-reactive protein elevation. Furthermore, biologics
      specific gene signatures in patients with RA indicate that looking for a biologic
      specific response pattern may be a potential future tool for predicting
      individual patient response.

PMID- 22872429
TI  - Health status one year after TransInguinal PrePeritoneal inguinal hernia repair
      and Lichtenstein's method: an analysis alongside a randomized clinical study.
AB  - BACKGROUND: The Lichtenstein technique is the treatment of first choice according
      to guidelines for primary inguinal hernia treatment. Postoperative chronic pain
      has been reported as complication in 15-40 % after Lichtenstein's repair. The
      postoperative effects on health status after open preperitoneal hernia repair
      have hardly been examined. Development of an open technique that combines the
      safe anterior approach of the Lichtenstein with the 'promising' preperitoneal
      soft mesh position was done; the transinguinal preperitoneal (TIPP) mesh repair.
      A double-blind prospective randomized controlled trial (TULIP trial,
      ISRCTN93798494) was conducted to compare different outcome parameters after TIPP
      or Lichtenstein, one parameter is topic of evaluation in this paper; the health
      status after TIPP and Lichtenstein for inguinal hernia repair. METHODS: The study
      protocol has been published. It was hypothesized that the health status of
      inguinal hernia patients would be better after the TIPP repair compared with the
      Lichtenstein technique. The size of this study was based on chronic pain as
      primary outcome measure. Three hundred and two patients were randomized. Patients
      and the outcome assessors were blinded. Follow-up was scheduled after 14 days, 3
      months, and 1 year. The three dimensions of possible errors were warranted.
      RESULTS: With regard to health status, significant differences were found in the
      dimensions 'physical pain' [difference: 6.1 (95 % CI 2.3-9.9, p = 0.002)] and
      'physical functioning' [difference: 3.5 (95 % CI 0.5-6.7, p = 0.023)], favoring
      the TIPP patients after 1 year. CONCLUSION: In conclusion, the SF-36 'physical
      function' and 'physical pain' dimensions after TIPP show significant better
      patient outcomes at 1 year compared with the Lichtenstein patients in this trial.
      These differences are in line with reported significant differences in less
      patients with postoperative chronic pain after TIPP compared with Lichtenstein at
      1 year.

PMID- 22872430
TI  - A comparison of two types of preperitoneal mesh prostheses in stoma surgery:
      application to an animal model.
AB  - INTRODUCTION: The aim of this study is to compare the integration of two types of
      prostheses (high and low density, written as HD and LD, respectively) implanted
      around the stoma to reinforce the abdominal wall to prevent parastomal
      eventration. The surgical technique used for preperitoneal placement of the
      prostheses is also described. MATERIALS AND METHODS: We performed terminal
      sigmoid colostomies on 16 porcine animals. In 8 of the animals, HD prostheses
      were placed around the stoma in preperitoneal position, while in the other 8, we
      implanted wide-pore LD prostheses using the same surgical technique. The
      following macroscopic variables were then measured: adhesion, extrusion,
      stenosis, and retraction. A morphological study was also carried out to evaluate
      the foreign body reaction and the formation of neovascularization and collagen.
      All animals were killed 3 months after surgery. RESULTS: Differences were
      observed with regard to retraction (47 +/- 17.8 % for HD vs. 55 +/- 19.4 % for
      LD) and extrusion (50 % for HD vs. 0 % for LD). These differences did not reach
      statistical significance. There was a great amount of scarring for both types of
      prostheses, with stomal stenosis being observed in all cases. The number and
      consistency of intra-abdominal adhesions was low and similar for both types of
      prostheses. Neither eventration nor necrosis was observed for either type. With
      regard to the tissue response, we observed both fibrosis and calcification
      phenomena in the peristomal areas of the LD prostheses. In the HD group, there
      was both a lower scarring response and a higher foreign body response, with the
      areas of the prostheses remaining intact. CONCLUSIONS: Both types of prostheses
      are appropriate for preperitoneal placement in the experimental model used,
      leading to few intra-abdominal adhesions. Still, due to their integration
      characteristics, LD prostheses are more appropriate for implanting around the
      colon since they do not seem to lead to extrusions. When using prostheses,
      however, it is also essential to consider the important phenomenon of retraction,
      which is more common with LD mesh.

PMID- 22872431
TI  - Two novel species Enterococcus lemanii sp. nov. and Enterococcus eurekensis sp.
      nov., isolated from a swine-manure storage pit.
AB  - A polyphasic taxonomic study using morphological, biochemical, chemotaxonomic and
      molecular genetic methods was performed on six strains of unknown Gram-positive,
      nonspore-forming, facultative anaerobic coccus-shaped bacteria isolated from a
      swine-manure storage pit. On the basis of the 16S rRNA, RNA polymerase alpha
      subunit (rpoA) and 60 kDa chaperonin (cpn60) gene sequence analyses, it was shown
      that all the isolates were enterococci but formed two separate lines of descent.
      Pairwise 16S rRNA gene sequence comparisons demonstrated that the two novel
      organisms were most closely related to each other (97.9 %) and to Enterococcus
      aquimarinus (97.8 %). Both organisms contained major amounts of C(16:0), C(16:1)
      omega7c, C(16:1) omega7c, and C(18:1) omega7c/12t/9t as the major cellular fatty
      acids. Based on biochemical, chemotaxonomic and phylogenetic evidence, the names
      Enterococcus lemanii sp. nov. (type strain PC32(T) = CCUG 61260(T) = NRRL B
      59661(T)) PPC27A = CCUG 61369; PPC38 = CCUG 61261 [corrected] and Enterococcus
      eurekensis sp. nov. (type strain PC4B(T) = CCUG 61259(T) = NRRL B-59662(T)) PPC15
      = CCUG 61368; PPC107 = CCUG 61372 [corrected] are proposed for these hitherto
      undescribed species.

PMID- 22872432
TI  - Norms, attitudes, and sex behaviors among women with incarcerated main partners.
AB  - Incarceration has been extensively linked with HIV and sexually transmitted
      infections (STIs). While a great deal of attention has been given to the risk
      behaviors of people who have been incarcerated, examination of the behaviors of
      partners of incarcerated individuals is also needed to understand the direct and
      indirect links between incarceration and HIV and to identify prevention avenues.
      In the present study, we hypothesize that incarceration is associated with risk
      behavior through attitudes and norms. The purpose of this paper is: (1) to
      describe the attitudes and norms about sexual behaviors that women have when a
      sexual partner is incarcerated; and (2) to examine the association between
      attitudes and norms with the behavior of having other sex partners while a main
      partner is incarcerated. In our sample (n = 175), 50 % of women reported having
      other sex partners while their partner was incarcerated. Our findings show that
      attitudes, descriptive norms (i.e., norms about what other people do), and
      injunctive norms (i.e., norms about what others think is appropriate) were
      associated with having other partners. Interventions designed for couples at pre-
      and post-release from prison are needed to develop risk reduction plans and
      encourage HIV/STI testing prior to their reunion. 

PMID- 22872435
TI  - Structural and upconversion studies of Er3+ codoped with CdS nanoparticles in sol
      gel glasses.
AB  - The Er(3+) codoped with CdS nanoparticles in sol-gel glass with an average
      particle size of about 10 nm have been synthesized by sol-gel method. The green
      and red up-conversion emissions centered at about 534, 560 and 680 nm,
      corresponding to the (2)H(11/2)->(4)I(15/2), (4)S(3/2)->(4)I(15/2) and (4)F(9/2)
      >(4)I(15/2) transitions of Er(3+), respectively; were detected by a 800 nm
      excitation. The two-photon absorption process is involved in the green and red up
      conversion emissions.

PMID- 22872433
TI  - Current interventions to reduce sexual risk behaviors and crack cocaine use among
      HIV-infected individuals.
AB  - The dual global epidemics of crack cocaine use and HIV have resulted in a large
      number of people living with HIV who use crack cocaine, many of whom continue to
      engage in unprotected sex. Crack use also increases the rate of HIV progression.
      Consequently, there is an urgent need for effective interventions to decrease
      crack use and unprotected sex and to improve antiretroviral therapy (ART)
      adherence in this population. This article reviews the recent published
      literature on interventions for reducing crack use and unprotected sex among
      people living with HIV. Only a few intervention outcome studies targeting
      exclusively HIV positive crack cocaine users were identified, whereas other
      studies used a mixed sample. Some interventions focused on reducing crack use and
      several focused on reducing sex-risk behaviors. Consequently, there is a critical
      need for efficacious interventions that address crack use, risky sex and ART
      adherence among people living with HIV.

PMID- 22872436
TI  - Luminescent sensor for carbonate ion based on lanthanide(III) complexes of
      1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A).
AB  - Lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
      (H(3)DO3A) are suggested as sensors for sensitive luminescence-based
      determination of a carbonate anion. Thermodynamic study of association of
      [Eu(H(2)O)(2)(DO3A)] with bidentate anionic ligands using luminescence
      spectroscopy reveals an affinity order CO(3)(2-) > oxalate(2-) > picolinate(-) >
      phthalate(2-) ~ citrate(3-); presumably as a consequence of an increasing chelate
      ring size. The ternary [Eu(DO3A)(picolinate)](-) and [Tb(DO3A)(picolinate)](-)
      complexes show improved photophysical properties due to the antenna effect of the
      picolinate anion. High quenching effect of carbonate anion and, to a lesser
      extent also oxalate, enables construction of a linear calibration plot utilizing
      optimized experimental conditions (e.g. c(LnL) = 0.1 mM, c(picolinate) = 2-5 mM,
      pH = 7.4, lambda(exc) = 286 nm, etc.) for carbonate determination in solution.
      Both sensors show a comparable sensitivity and the detection limit of about 0.4
      mM. In order to improve the photophysical properties of Ln(III) sensor by shift
      of excitation wavelength about 40 nm to VIS range, the isoquinoline-3-carboxylic
      acid (IQCA) as antenna ligand was employed instead of picolinic acid. The
      analysis of commercial samples of European mineral waters was carried out and
      they were compared to the results obtained by capillary isotachophoresis to
      confirm there is no inherent (systematic) error to the present analysis. The
      Ln(III) sensor with IQCA is recommended since it has a better robustness than
      that with picolinate. The present analytical method is simple and rapid, and it
      is useful for sensitive determination of bicarbonate/carbonate concentration in
      water samples under aerobic conditions.

PMID- 22872437
TI  - Effect of milling on particle shape and surface energy heterogeneity of needle
      shaped crystals.
AB  - PURPOSE: Milling and micronization of particles are routinely employed in the
      pharmaceutical industry to obtain small particles with desired particle size
      characteristics. The aim of this study is to demonstrate that particle shape is
      an important factor affecting the fracture mechanism in milling. METHODS: Needle
      shaped crystals of the beta polymorph of D-mannitol were prepared from
      recrystallization in water. A portion of the recrystallized materials was ball
      milled. Unmilled and milled sieved fractions of recrystallized D-mannitol were
      analyzed by dynamic image analysis (DIA) and inverse gas chromatography (IGC) at
      finite concentration to explain the breakage/fracture behavior. RESULTS: In the
      process of ball-milling, D-mannitol preferentially fractured along their shortest
      axis, exposing (011) plane with increased hydrophilicity and increased bounding
      rectangular aspect ratio. This is in contrary to attachment energy modeling which
      predicts a fracture mechanism across the (010) plane with increased
      hydrophobicity, and small change in particle shape. CONCLUSIONS: Crystal size,
      and more importantly, crystal shape and facet-specific mechanical properties, can
      dictate the fracture/cleavage behavior of organic crystalline materials. Thorough
      understanding of the crystal slip systems, combining attachment energy prediction
      with particle shape and surface characterization using DIA and IGC, are important
      in understanding fracture behavior of organic crystalline solids in milling and
      micronization.

PMID- 22872438
TI  - Tricuspid valve-in-valve implantation: the transjugular approach.

PMID- 22872439
TI  - Pulmonary artery sarcoma.

PMID- 22872440
TI  - Re: Results of orthotopic heart transplantation for failed palliation of
      hypoplastic left heart.

PMID- 22872441
TI  - Clinical research to optimize the Fontan concept: a long, difficult, but
      rewarding, journey.

PMID- 22872442
TI  - It is time to revisit the theory of acute conduction block: efficacy of high
      intensity focused ultrasound epicardial ablation.

PMID- 22872443
TI  - Steering trajectories in magnetically actuated colloidal propellers.
AB  - Microscale colloidal doublets composed of DNA-linked paramagnetic particles and
      floating close to a surface are able to propel in viscous fluids when subjected
      to external precessing magnetic fields. We show here that for certain values of
      the precession angle, the composite particles can be steered into tilted rather
      than linear trajectories characterized by a non-vanishing lateral velocity during
      motion. We extend the original model developed in Phys. Rev. Lett. 101, 218304
      (2008) in order to explain this phenomenon, by including high-order corrections
      in the expansion of the director field and demonstrate the validity of this
      approach by comparing the analytical results with the experimental data.

PMID- 22872444
TI  - Molecular characteristics of fibrolamellar hepatocellular carcinoma.
AB  - Fibrolamellar hepatocellular carcinoma (FLC) occurs in non-cirrhotic liver and
      the etiopathogenesis is still obscure. Both hepatocellular and cholangiocellular
      markers are expressed in the tumor, however, molecular alterations and altered
      pathways playing role in the tumor pathogenesis are not clearly identified. The
      purpose of the present study was to compare the expression level of EGFR,
      syndecan-1 and beta-catenin in FLC, conventional hepatocellular carcinoma (cHCC)
      and cholangiocellular carcinoma (CCC) and to investigate the possibility of
      mutation both in EGFR and K-RAS. Eight FLCs were compared with 7 cHCCs, 7 CCCs
      and 5 normal liver samples. Cytokeratins 7, 8, 18, 19, HepPar1 (HSA), EGFR,
      syndecan-1 (CD138) and beta-catenin were detected by immunohistochemistry. In
      addition EGFR, beta-catenin and syndecan-1 were evaluated by digital morphometry
      and K-RAS, EGFR mutations in FLC cases using paraffin-embedded samples. All FLCs
      were positive for HepPar1 (HSA) and cytokeratins 7, 8, 18, but negative for
      cytokeratin 19 by immunohistochemistry. EGFR was significantly overexpressed in
      all three tumor types, being highest in FLCs (p = 0,0001). EGFR, K-RAS mutation
      analyses revealed no mutations in exons studied in FLCs. Our findings proved that
      expression of EGFR is higher in FLC than in other types of primary malignant
      hepatic tumors and no K-RAS mutation can be detected, so FLC is a good candidate
      for anti-EGFR treatment.

PMID- 22872445
TI  - Antibiotic susceptibility profile of Mycobacterium avium subspecies hominissuis
      is altered in low-iron conditions.
AB  - OBJECTIVES: Antibiotic susceptibility testing of the Mycobacterium avium complex
      is often characterized by a lack of correlation between in vitro results and
      clinical response. The reason for this discrepancy might lie in the difference
      between in vitro susceptibility testing conditions and the actual environment
      experienced by mycobacteria in the host. The availability of iron is one such
      difference, which is limited in host macrophages upon infection, but abundant in
      susceptibility testing media. Accordingly, the aim of our study was to determine
      whether iron limitation affects the antibiotic susceptibility profile of M. avium
      subspecies hominissuis. METHODS: Susceptibilities to multiple antibiotics
      targeting various cellular processes were determined in media with normal- and
      low-iron concentrations using the resazurin microplate assay. Differences in
      susceptibilities were evaluated by monitoring changes in the MIC and growth
      inhibition at subinhibitory antibiotic concentrations (sub-MICs). RESULTS:
      Cultures grown in low-iron conditions were less susceptible to the DNA synthesis
      inhibitors 6-mercaptopurine and levofloxacin at sub-MICs. Decreased
      susceptibility to the protein synthesis inhibitors azithromycin (>2-fold) and
      streptomycin (at sub-MICs) was observed only during adaptation to low-iron
      conditions. On the contrary, increased susceptibility to antibiotics that
      interfere with cell wall synthesis [isoniazid (4-fold), d-cycloserine (2-fold)
      and ethambutol (at sub-MICs)], mycobactin synthesis [4-aminosalicylate (at sub
      MICs)] and mRNA synthesis [rifampicin (4-fold)] was observed in low-iron
      conditions. CONCLUSIONS: The susceptibility profile in low-iron conditions
      significantly differs from that observed in normal-iron conditions. Mimicking the
      host environment in terms of iron availability should be considered for in vitro
      susceptibility testing of mycobacteria, especially for antibiotics interfering
      with iron metabolism, such as 4-aminosalicylate.

PMID- 22872446
TI  - OXA-23-producing Acinetobacter species from horses: a public health hazard?

PMID- 22872447
TI  - Development and validation of a new method to simultaneously quantify triazoles
      in plasma spotted on dry sample spot devices and analysed by HPLC-MS.
AB  - OBJECTIVES: Therapeutic drug monitoring (TDM) of triazoles is widely used in
      clinical practice to optimize therapy. TDM is limited by technical problems and
      cost considerations, such as sample storage and dry-ice shipping. We aimed to
      develop and validate a new method to analyse itraconazole, posaconazole and
      voriconazole in plasma spotted on dry sample spot devices (DSSDs) and to quantify
      them by an HPLC system. METHODS: Extraction from DSSDs was done using n
      hexane/ethyl acetate and ammonia solution. Samples were analysed using HPLC with
      mass spectrometry (HPLC-MS). Accuracy and precision were assayed by inter- and
      intra-day validation. The stability of triazoles in plasma spotted on DSSDs was
      investigated at room temperature for 1 month. The method was compared with a
      validated standard HPLC method for quantification of triazoles in human plasma.
      RESULTS: Mean inter- and intra-day accuracy and precision were <15% for all
      compounds. Triazoles were stable for 2 weeks at room temperature. The method was
      linear (r(2) > 0.999) in the range 0.031-8 mg/L for itraconazole and
      posaconazole, and 0.058-15 mg/L for voriconazole. High sensitivity was observed;
      limits of detection were 0.008, 0.004 and 0.007 mg/L for itraconazole,
      posaconazole and voriconazole, respectively. A high degree of correlation (r(2) >
      0.94) was obtained between the DSSD method and the standard method of analysis.
      CONCLUSIONS: The method that we developed and validated to quantify triazoles in
      human plasma spotted on DSSDs is accurate and precise. It overcomes problems
      related to plasma sample storage and shipment, allowing TDM to be performed in a
      cheaper and safer manner.

PMID- 22872448
TI  - Development of nanocapsules bearing doxorubicin for macrophage targeting through
      the phosphatidylserine ligand: a system for intervention in visceral
      leishmaniasis.
AB  - OBJECTIVES: The purpose of this study was to explore the applicability, targeting
      potential and drug delivery to specialized phagocytes via phosphatidylserine (PS)
      specific ligand-anchored nanocapsules (NCs) bearing doxorubicin. METHODS: The
      layer-by-layer method was utilized to prepare NCs having a nanoemulsion core
      loaded with doxorubicin (NCs-DOX), which was further grafted with PS. PS-coated
      NCs (PS-NCs-DOX) were compared with NCs-DOX for in vitro targeting ability by
      studying uptake by macrophages, intracellular localization, in vivo
      pharmacokinetics and organ distribution studies. The in vivo antileishmanial
      activity of free doxorubicin, NCs-DOX and PS-NCs-DOX was tested against visceral
      leishmaniasis in Leishmania donovani-infected hamsters. RESULTS: Flow cytometric
      data revealed 1.75-fold enhanced uptake of PS-NCs-DOX in J774A.1 macrophage cell
      lines compared with NCs-DOX. In vivo organ distribution studies in Wistar rats
      demonstrated a significantly higher extent of accumulation of PS-NCs-DOX compared
      with NCs-DOX in macrophage-rich organs, particularly in liver and spleen. Highly
      significant antileishmanial activity (P < 0.05 compared with NCs) was observed
      with PS-NCs-DOX, causing 85.23% +/- 4.49% inhibition of splenic parasitic burden.
      NCs-DOX and free doxorubicin caused only 72.88% +/- 3.87% and 42.85% +/- 2.11%
      parasite inhibition, respectively, in Leishmania-infected hamsters (P < 0.01 for
      PS-NCs-DOX versus free doxorubicin and NCs-DOX versus free doxorubicin).
      CONCLUSIONS: We conclude that the PS targeting moiety can provide a new insight
      for efficient drug delivery to specialized macrophages and thus may be developed
      for effective use in macrophage-specific delivery systems, especially for
      leishmaniasis.

PMID- 22872449
TI  - IncI1/ST3 plasmids contribute to the dissemination of the blaCTX-M-1 gene in
      Escherichia coli from several animal species in France.

PMID- 22872450
TI  - Japanese diabetic patients with Werner syndrome exhibit high incidence of cancer.

PMID- 22872451
TI  - Characterization of wheat DArT markers: genetic and functional features.
AB  - Diversity array technology (DArT) markers are largely used for mapping, genetic
      diversity, and association mapping studies. For years, they have been used as
      anonymous genomic markers, as their sequences were not known. As the sequences of
      2,000 wheat DArT clones are now available, this study was designed to analyze
      these sequences with bioinformatic approaches, and to study the genetic features
      of a subset of 291 markers positioned on the A and B genomes in three durum wheat
      genetic maps. A set of 1,757 non-redundant sequences was identified, and used as
      queries for similarity searches. Analysis of the genetic positions of markers
      corresponding to nearly identical sequences indicates that redundancy of
      sequences is one of the factors that explains the clustering of these markers in
      specific genomic regions. Of a total of 1,124 DArT clones (64 %) that represent
      putatively expressed sequences, putative functions are proposed for more than 700
      of them. Of note, many clones correspond to genes that are related to disease
      resistance, as characterized by leucine-rich repeat domains, and 40 of these
      clones are positioned in the three genetic maps presented in this study. Finally,
      DArT markers have been used to find syntenic regions in the Brachypodium and rice
      genomes. In conclusion, the analyses herein presented contribute to explain the
      main features of DArT markers observed in genetic maps, as clustering in short
      chromosome regions. Moreover, the attribution of putative gene functions for more
      than 700 sequences makes these markers an optimal tool for collinearity studies
      or for the identification of candidate genes.

PMID- 22872452
TI  - Recurrence in giant cell tumour of bone: imaging features and risk factors.
AB  - PURPOSE: This study was done to investigate X-ray, computed tomography (CT) and
      magnetic resonance (MR) imaging features of recurrence in giant cell tumour of
      bone (GCTB) and to evaluate risk factors. MATERIALS AND METHODS: Medical records
      and imaging data were reviewed for 55 cases of recurrent GCTB. All images were
      reviewed retrospectively and independently by two radiologists experienced in
      skeletal musculature. The common radiological findings; factors related to tumour
      recurrence such as gender, age, location; pathological fracture, Campanacci
      grading and surgical procedure were analysed by nonparametric test (Mann-Whitney
      U test for two independent samples test and Kruskal-Wallis H test for multiple
      independent samples test). p values <0.05 were considered to indicate a
      statistically significant difference. RESULTS: The imaging features of recurrent
      GCTB were as follows: osteolytic destruction or bone resorption of graft bone or
      around the polymethylmethacrylate (PMMA), soft tissue mass formation and
      expansile change. Tumour parenchyma showed markedly heterogeneous enhancement,
      except for necrotic cystic cavities, on contrast-enhanced MR images. Wide
      resection had a smaller (p=0.031) risk of local recurrence than did intralesional
      curettage. There was no statistical significance in gender, age, location,
      pathological fracture and Campanacci staging (p>0.05). CONCLUSIONS: The risk of
      recurrence in GCTB was influenced by the type of surgery and adjuvants. Bone
      transformaresorption, soft tissue mass formation and aggravated expansile change
      are reliable signs of recurrence on imaging.

PMID- 22872453
TI  - Endometrial carcinoma: MR staging and causes of error.
AB  - PURPOSE: This study was undertaken to prospectively determine the diagnostic
      capabilities of magnetic resonance (MR) imaging in detecting myometrial and
      cervical invasion and lymph node involvement in endometrial carcinoma and to
      identify the causes of errors in staging endometrial carcinoma. MATERIALS AND
      METHODS: Twenty consecutive patients with a histological diagnosis of endometrial
      carcinoma underwent preoperative MR imaging. MR findings were compared with
      surgical staging, considered as the standard of reference. RESULTS: In assessing
      myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40%
      specificity, 80% positive predictive value (PPV), and 40% negative predictive
      value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100%
      sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node
      involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and
      NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour,
      adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were
      caused by dilatation and curettage. CONCLUSIONS: MR imaging is a reliable
      technique for preoperative evaluation of endometrial carcinoma. Its main
      limitation is differentiating between stage IA and IB carcinomas, which is not
      highly important for surgical planning. Cooperation between the gynaecologist and
      radiologist is mandatory to avoid staging errors.

PMID- 22872454
TI  - Breast cancer surveillance in patients treated by radiotherapy for Hodgkin's
      lymphoma.
AB  - PURPOSE: The authors evaluated the relative risk of developing radiation-induced
      breast cancer (BC) in women treated with radiotherapy for Hodgkin's disease (HD)
      and analysed the imaging features of these breast neoplasms. MATERIALS AND
      METHODS: We retrospectively studied 54 women who had all undergone radiotherapy
      between 1980 and 2010 (median age, 36.6 years). Women aged <=30 years were
      screened with clinical breast examination, ultrasound (US) and, if necessary,
      mammography; women >30 years had clinical breast examination, US and mammography.
      Three women underwent magnetic resonance (MR) imaging as well. RESULTS:
      Mammography detected seven invasive breast cancers in 6/54 women (11.1%). Median
      age at diagnosis was 26.1 years for HD and 42.4 for breast cancer. Breast cancer
      was diagnosed following a median latent period from radiotherapy of 15.1 years.
      Mean radiation dose was 37.6 Gy in women who developed breast cancer and 31.3 Gy
      in the other women. CONCLUSIONS: In our study, women who were exposed to
      radiation for HD had a 6.2-fold higher risk of developing breast cancer than the
      general population. In consideration of the young age and high breast density,
      women aged <=30 years should be monitored by US and MR imaging; women aged >30
      years should be monitored by US, mammography and, when necessary, MR imaging.

PMID- 22872455
TI  - Interventional radiology in the treatment of early postoperative biliary
      complications.
AB  - PURPOSE: We sought to evaluate the feasibility and efficacy of percutaneous
      treatment of early postoperative biliary complications. The primary aims were to
      evaluate clinical and technical success and complications and perioperative
      mortality, and secondary aims were to evaluate treatment duration and recurrence
      rate. MATERIALS AND METHODS: Between March 2007 and March 2010, 75 patients (42
      men and 33 women; age range, 17-88 years; mean age, 60.8 years) underwent
      interventional radiology procedures to treat early postoperative biliary
      complications of biliary and pancreatic-duodenal surgery with biliodigestive
      anastomosis (37.7%), laparoscopic cholecystectomy (30.6%), hepatic resection
      (21.1%) and several other surgical procedures (10.6%). Complications included
      fistulas (73%), stenoses (20%) and complete bile duct transections (7%). RESULTS:
      Interventional radiology achieved complete clinical success in 74 cases (85.9%)
      and in particular in 95.2% of fistulas, 76.5% of stenoses and 33.3% of complete
      bile duct transections. Mean indwelling catheter time was 34.9 days, with an
      average of 4.1 procedures. There were two cases of severe haemobilia (2.3%).
      Minor complications occurred in 7% of cases. Perioperative mortality rate was
      1.2% and overall recurrence rate 6.7% (range, 1-18 months; mean, 10 months), with
      recurrences occurring predominantly in stenoses. All patients were retreated
      successfully. CONCLUSIONS: Percutaneous procedures are feasible, effective and
      safe for treating early postoperative biliary complications. They provide a
      valuable alternative to presendoscopy, which is precluded in many of these
      patients, and to surgery, which has higher morbidity and mortality rates.

PMID- 22872456
TI  - Contrast-enhanced MR imaging of the breast: association between asymmetric
      increased breast vascularity and ipsilateral cancer in a consecutive series of
      197 patients.
AB  - PURPOSE: This study was done to estimate the diagnostic performance of an
      asymmetric increase in breast vascularity (AIBV) for ipsilateral cancer.
      MATERIALS AND METHODS: A total of 197 patients without previous breast
      interventions underwent bilateral contrast-enhanced (gadoterate meglumine, 0.1
      mmol/kg) magnetic resonance (MR) imaging. Vessels >-2 mm in diameter and >= 3 cm
      in length were counted on maximum intensity projections: a difference >= 2 in
      number between the two breasts was considered AIBV. Pathology or >= 1 year follow
      up served as a reference standard. The difference in sensitivity of AIBV between
      invasive and ductal carcinoma in situ (DCIS) as well as the association between
      AIBV and the diameter of invasive lesions or the histological grade were
      evaluated using chi(2) test. RESULTS: Pathology revealed 82 malignancies and 20
      benign lesions: 70 invasive carcinomas (57 ductal, nine lobular, three mucinous,
      one papillary) and 12 DCIS: 10 fibroadenomas, two papillomas, two atypical ductal
      hyperplasias and six other benign lesions. The remaining 95 patients were
      negative at follow-up. Sensitivity of AIBV was 74% (61/82), specificity 94%
      (108/115), accuracy 86% (169/197), positive predictive value 90% (61/68) and
      negative predictive value 84% (108/129). Sensitivity for invasive cancers (80%;
      56/70) was significantly higher than that for DCIS (42%; 5/12) (p<0.001). For
      invasive cancers, sensitivity was 40% (2/5) for lesions <= 9 mm in diameter, 69%
      (9/13) for those 10-14 mm, 79% (15/19) for those 15-19 mm and 91% (30/33) for
      those >= 20 mm (p<0.001). The G3 lesion rate was 49% (27/55) among true positives
      and only 7% (1/14) among false negatives (p=0.009). CONCLUSIONS: An association
      between AIBV and ipsilateral cancer exists, particularly for invasive cancers >=
      20 mm or with high pathologic grade.

PMID- 22872457
TI  - Perfusion computed tomography assessments of peri-enhancing brain tissue in high
      grade gliomas.
AB  - PURPOSE: This study was undertaken to identify tumoural infiltration of peri
      enhancing brain tissue in patients with glioblastoma by means of perfusion
      computed tomography (PCT) parameters, cerebral blood volume (CBV) and
      permeability surface (PS). MATERIALS AND METHODS: Eight patients with surgically
      treated glioblastoma who were eligible for radiotherapy and nine patients with
      brain metastases from lung and breast cancer underwent CT before and after
      injection of contrast medium. CBV and PS were calculated in the contrast
      enhancing lesion area, in the area of perilesional oedema and in the normal
      appearing white matter (NAWM), normalised to contralateral symmetrical areas.
      RESULTS: No significant differences were found for normalised CBV (nCBV) and nPS
      in NAWM regions between metastasis and glioma. Significant differences in nPS
      (p<0.005) were found between the typically vasogenic oedema surrounding the
      metastases and signal alteration surrounding the glial neoplasm. On the contrary,
      no significant differences were detected in the same areas for nCBV. CONCLUSIONS:
      PCT can analyse the histopathological substrate underlying the hypodense
      peritumoural halo and differentiate between vasogenic oedema and neoplastic
      infiltration on the basis of the PS parameter. In our study, PS was more
      informative than CBV. These findings can be used to integrate plans for radiation
      therapy and/or surgery.

PMID- 22872458
TI  - [Bronchial and nonbronchial systemic artery embolization in managing haemoptysis:
      31 years of experience].
AB  - PURPOSE: The authors report on 31 years of experience with bronchial (BAE) and/or
      nonbronchial (NBAE) systemic artery embolisation for managing haemoptysis.
      MATERIALS AND METHODS: A total of 534 patients who underwent bronchial artery
      angiography for haemoptysis between 1979 and 2010 were retrospectively evaluated.
      Of these patients, 477 (89%) had active bleeding and underwent BAE and/or NBAE
      (295 males and 182 females, aged between 12 and 71 years). Embolisation
      techniques, materials, major and minor complications and relapses were recorded.
      RESULTS: Complete resolution of haemoptysis was achieved within 24 h in 458/477
      (96%) cases and within 48 h in 2% of cases. The aetiology of haemoptysis was as
      follows: cystic fibrosis (23%), bronchiectasis (13%), tuberculosis sequelae (8%),
      chronic obstructive pulmonary disease (COPD) (6%) and no apparent cause (21%).
      Major complications were recorded in 3/477 (0.6%): stroke (n=1), transient
      ischaemic attack (TIA) (n=1) and transient quadriplegia (n=1). Minor
      complications were recorded in 143/477 (30%): chest pain 86/143 (60%) and
      dysphagia 29/143 (20%). During a mean follow-up period of 14 (8-36) months,
      haemoptysis recurrence was observed in 42/110 cases (38%) of cystic fibrosis and
      in 77/367 cases of other diseases (21%). CONCLUSIONS: BAE and NBAE are effective
      and safe for acute treatment of haemoptysis, with low recurrence and complication
      rates. Interventional radiologist experience is crucial to the successful
      haemoptysis control and preventing complications.

PMID- 22872459
TI  - Treatment of invasive male breast cancer: a 40-year single-institution
      experience.
AB  - PURPOSE: We conducted a retrospective analysis to evaluate the management and
      outcome of invasive male breast cancer treated in a single-institution over a
      period of 40 years. MATERIALS AND METHODS: We reviewed the clinical and
      pathological features of 60 male patients affected by breast carcinoma treated at
      our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to
      histological type and the updated 2010 TNM classification of malignant tumours.
      RESULTS: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD),
      4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to
      disease progression and 12 (20%) due to other causes. At univariate analysis for
      overall survival, pathological tumour size (p=0.031), histological subtype
      (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death.
      At multivariate analysis, independent death predictors were advanced pathological
      tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform
      histological type (p=0.0003). CONCLUSIONS: In consideration of the rarity of the
      disease, many issues are still being debated, and future collaborative studies
      are required. However, our experience confirms the prognostic role of greater
      pathological tumour size and positive nodal status as unfavourable features for
      survival in male breast cancer.

PMID- 22872460
TI  - Palliative embolisation for advanced bone sarcomas.
AB  - PURPOSE: Managing patients with advanced bone sarcomas - namely, recurrent,
      unresectable and metastatic - is mostly aimed at palliation. The role of
      embolisation for pain relief for these patients has not been previously reported.
      We therefore performed this study to emphasise the palliative role of
      embolisation for pain relief of advanced bone sarcoma patients. MATERIALS AND
      METHODS: We retrospectively studied 43 patients with advanced bone sarcomas
      treated with palliative embolisation with N-2-butyl-cyanoacrylate from 2004 to
      2011. All patients had primary treatments including chemotherapy, radiation
      therapy, radiofrequency thermal ablation, and/or surgery for their advanced
      sarcomas and were referred for embolisation as end-stage treatment for continuous
      severe local pain. The effect of embolisation was evaluated with a pain score
      scale and analgesic use. Mean follow-up was 7 (range, 1-19) months); all patients
      were dead at the last follow-up. RESULTS: In all patients, angiography showed
      increased pathological vascularisation of the sarcomas; three to six feeding
      vessels were embolised in each procedure. Almost complete pain relief and >50%
      reduction in analgesic use was experienced by 36 patients with highly
      hypervascular sarcomas and sarcomas in the pelvis and shoulder girdle. Moderate
      pain relief and 50% reduction in analgesic use was experienced by seven patients
      with spinal and sacral lesions. Within the available follow-up, no patient had
      recurrent pain with the same intensity as before embolisation. All patients
      experienced ischaemic pain at the site of embolisation that resolved completely
      with analgesics. Six patients with advanced pelvic bone sarcomas experienced
      paraesthesias at the distribution of the sciatic nerve that resolved completely
      with methylprednisolone. CONCLUSIONS: Embolisation is a safe and effective local
      palliative treatment for patients with advanced sarcomas, providing optimum pain
      relief with the least discomfort and the possibility of minor complications only.

PMID- 22872461
TI  - Three-dimensional rotational angiography for craniotomy planning and
      postintervention evaluation of intracranial aneurysms.
AB  - PURPOSE: The authors evaluated the usefulness of three-dimensional rotational
      angiography (3DRA) in surgical planning and postoperative evaluation of cerebral
      aneurysms. MATERIALS AND METHODS: A total of 111 consecutive aneurysms in 100
      patients (32 emergency referrals due to haemorrhage) were evaluated with 3DRA
      over a period of 3 years. The rotational study was always performed with a single
      injection of 20 cc of contrast agent in the afferent vessel after diagnostic
      cerebral angiography in the two orthogonal projections. Three-dimensional
      reconstructions were obtained for the pre- and postoperative assessment. RESULTS:
      Three-dimensional RA provides a virtual view of the surgical field with the same
      orientation required for the surgical approach and, compared with surgical
      findings, reliably defined location, orientation, morphology and relationship
      with parent vessels of the aneurysm in all cases. Postoperatively, it allowed
      better assessment of any residual lesion and of the relationship between surgical
      clips and parent vessels, compared with standard 2D angiography. CONCLUSIONS:
      3DRA is a reliable method for preliminary assessment of cerebral aneurysms
      undergoing surgery. It provides multiple projections with a preview of the
      surgical field and study of lesion characteristics, which can help achieve faster
      and safer surgery. Compared with 2D angiography, the 3D model, with its multiple
      views, allows better assessment of postoperative outcomes. The method also
      significantly reduces the number of angiographic projections and therefore
      radiation and contrast-medium dose to the patient.

PMID- 22872462
TI  - Diagnostic accuracy and agreement between whole-body diffusion MRI and bone
      scintigraphy in detecting bone metastases.
AB  - PURPOSE: This study was done to determine the diagnostic value of whole-body
      magnetic resonance using diffusion-weighted imaging with background suppression
      (WB-DWIBS) for detecting bone metastases compared with whole-body bone
      scintigraphy (WB-BS). MATERIALS AND METHODS: Twenty-three patients with solid
      tumours underwent both WB-DWIBS imaging and WBBS. A nuclear medicine specialist
      interpreted WB-BS images and two blinded radiologists, first independently and
      then jointly, interpreted the WB-DWIBS images by completing a reading grid
      categorising the skeletal segments. Cohen's k statistic was used to determine
      interobserver agreement in reading the WB-DWIBS images and the agreement between
      WB-BS and WB-DWIBS. Sensitivity and specificity were calculated per patient and
      per lesion. RESULTS: Interobserver agreement in reading the WBDWIBS images was
      substantial or good, with kappa=0.68. Analysis of agreement between the nuclear
      physician's and the radiologists' readings provided kappa=0.87 [95% confidence
      interval (CI)=0.76-0.98)] Per-lesion analysis gave a sensitivity of 80% (95%
      CI=75-85) and a specificity of 98.2% (95% CI=96.5-99.8). CONCLUSIONS: We found a
      good level of interobserver agreement for the WB-DWIBS images and an excellent
      level of agreement in the subjective judgement of presence or absence of disease
      between WB-BS and WB-DWIBS after consensual double reading. WB-DWIBS has the same
      specificity as WB-BS in detecting bone metastases. The anatomical sites
      exhibiting the highest level of disagreement between WB-DWIBS and WB-BS are the
      pelvis, the coccyx, and the sternum, all sites at which detection with WB-BS has
      the greatest limitations.

PMID- 22872463
TI  - Evaluation of intracranial aneurysms with high-resolution MR angiography using
      single-artery highlighting technique: correlation with digital subtraction
      angiography.
AB  - PURPOSE: The authors investigated the effectiveness of high-resolution magnetic
      resonance angiography (MRA) using a single-artery highlighting technique for the
      accurate diagnosis of intracranial aneurysms at 3.0 T in a large cohort of
      patients with suspected intracranial aneurysms against the current gold standard,
      i.e. cerebral angiography. METHODS: A total of 307 patients with suspected
      aneurysms were referred for three-dimensional time-of-flight MRA (3D-TOF-MRA)
      prior to digital subtraction angiography (DSA). We summarised patient-based,
      aneurysm-based and vessel-based diagnostic performance parameters, namely,
      accuracy, sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) for detecting intracranial aneurysms with 3D-TOF-MRA.
      Interobserver agreement was calculated with the kappa (kappa) statistic. RESULTS:
      Patient-based accuracy was 98.1%, sensitivity 99.5%, specificity 95.3%, PPV 97.6%
      and NPV 99% according to observer A; and 97.7%, 99.5%, 94.3%, 97.1% and 99%,
      respectively, according to observer B. Aneurysmbased accuracy was 98.3%,
      sensitivity 99.6%, specificity 95.2%, PPV 98.1% and NPV 99% according to observer
      A, and 98.0%, 99.6%, 94.3%, 97.7% and 99%, respectively, according to observer B.
      Vessel-based accuracy was 99.0%, sensitivity 99.6%, specificity 98.7%, PPV 97.8%,
      and NPV 99.7% according to observer A, and 98.9%, 99.6%, 98.5%, 97.3%, and 99.7%,
      respectively, according to observer B. Interobserver reading differences were not
      significant. The interobserver agreement was good, with a kappa (kappa) value of
      0.931 for patient-based evaluation, 0.934 for aneurysmbased evaluation and 0.953
      for vessel-based evaluation. CONCLUSIONS: Our results demonstrate the
      effectiveness of high-resolution MRA using a single-artery-highlighting technique
      for accurate diagnosis of intracranial aneurysms in a large cohort of patients
      with suspected aneurysms.

PMID- 22872465
TI  - Prevalence of synthetic cannabinoids in U.S. athletes: initial findings.
AB  - A number of synthetic cannabinoids such as JWH-018 and JWH-073 have been
      incorporated into "spice" products. Despite having labels warning against human
      consumption, the products are smoked for their cannabinoid-like effects and the
      extent of their use by athletes has not been adequately described. Urine samples
      collected from 5,956 athletes were analyzed by high-performance liquid
      chromatography-tandem mass spectrometry for the presence of JWH-018, JWH-073, and
      their metabolites. Metabolites of JWH-018 and/or JWH-073 were detected in 4.5% of
      the samples. Metabolites of JWH-018 and JWH-073, only JWH-018, and only JWH-073
      were detected in 50%, 49%, and approximately 1% of positive samples,
      respectively. In total, JWH-018 metabolites were detected in 99% (50% + 49%) and
      JWH-073 metabolites were detected in approximately 50% (49% + 1%) of the positive
      samples. Parent JWH-018, JWH-018-2-OH-indole, and JWH-018-4-OH-indole were not
      detected in any of the samples. All samples in which JWH-073 metabolites were
      detected contained JWH-073-N-butanoic acid. Parent JWH-073 and its N-(4-OH
      butyl), 4-OH-indole, 5-OH-indole, and 7-OH-indole metabolites were not detected.
      Given the number of synthetic cannabinoids that have been synthesized, their
      limited regulation, and the prevalence of JWH-018 and JWH-073 metabolites
      detected in the athletes, these compounds should remain a priority for anti
      doping programs.

PMID- 22872464
TI  - Pressor response to oral tyramine and monoamine oxidase inhibition during
      treatment with ralfinamide (NW-1029).
AB  - Ralfinamide, an original Na(+) channel blocker developed for the treatment of
      chronic pain, inhibits monoamineoxidase-B with no apparent effect on
      monoamineoxidase-A. To evaluate the pressor response to oral tyramine under
      fasting conditions during treatment with ralfinamide in healthy normotensive
      subjects. Ten women and 10 men aged 52.9 +/- 5.5, sensitive to the oral tyramine
      pressor effect in the dose range 200-400 mg, received ralfinamide 320 mg daily
      during 7 days of confinement. Starting on day 5, ascending doses of tyramine 50,
      100 and 200 mg were daily administered to subjects, who had responded to 200 mg
      at screening, and 100, 200 and 400 mg to the 400 mg responders. Vital parameters
      were monitored. The systolic blood pressure peak (DeltaSBP), the time to achieve
      the peak (Deltat) and the area under the pressure curve (over baseline) were
      calculated. DeltaSBP >= 30 mmHg were measured for one subject with tyramine 200
      mg and for 11 subjects with 400 mg, whilst DeltaSBP was <30 mmHg for eight
      subjects at all the tested doses. DeltaSBP, Deltat and AUC after co-treatment
      with ralfinamide and tyramine were not significantly different from those
      measured after tyramine alone. Ralfinamide did not potentiate the pressor
      response to single oral doses of tyramine from 50 to 400 mg. These preliminary
      results give an evidence for the specificity of ralfinamide for MAO-B in
      comparison with MAO-A, analogously to the observations previously done for
      safinamide. Dietary tyramine restrictions may not be necessary in neuropathic
      pain patients receiving ralfinamide as a therapy.

PMID- 22872466
TI  - Gambling participation and problem gambling severity among rural and peri-urban
      poor South African adults in KwaZulu-Natal.
AB  - Poor South Africans are significantly poorer and have lower employment rates than
      the subjects of most published research on gambling prevalence and problem
      gambling. Some existing work suggests relationships between gambling activity
      (including severity of risk for problem gambling), income, employment status and
      casino proximity. The objective of the study reported here is to establish the
      prevalence of gambling, including at risk and pathological gambling, and the
      profile of gambling activities in two samples of poor South African adults living
      in a rural and a peri-urban community. A total of 300 (150 male, 150 female)
      adults in KwaZulu-Natal, South Africa in communities selected using census data,
      completed the Problem Gambling Severity Index and a survey of socioeconomic and
      household information, and of gambling knowledge and activity. It was found that
      gambling was common, and-except for lottery participation-mostly informal or
      unlicensed. Significant differences between rural and peri-urban populations were
      found. Peri-urban subjects were slightly less poor, and gambled more and on a
      different and wider range of activities. Problem and at risk gamblers were
      disproportionately represented among the more urbanised. Casino proximity
      appeared largely irrelevant to gambling activity. 

PMID- 22872467
TI  - Estradiol acutely inhibits whole body lipid oxidation and attenuates lipolysis in
      subcutaneous adipose tissue: a randomized, placebo-controlled study in
      postmenopausal women.
AB  - CONTEXT: Estradiol (E(2)) promotes and maintains the female phenotype
      characterized by subcutaneous fat accumulation. There is evidence to suggest that
      this effect is due to increased anti-lipolytic alpha2A-adrenergic receptors, but
      whether this requires long-term exposure to E(2) or is an immediate effect is not
      clear. OBJECTIVE: To study acute effects of a single dose (4 mg) of 17beta-E(2)
      on regional and systemic lipolysis. METHODS: Sixteen postmenopausal women (age,
      595 years; weight, 6710 kg; and BMI, 24.82.9) were studied in a crossover design:
      i) placebo and ii) 4 mg E(2). Basal and adrenaline-stimulated regional lipolysis
      was assessed by microdialysis and substrate oxidation rates by indirect
      calorimetry. Tissue biopsies were obtained to assess lipoprotein lipase activity
      and mRNA expression of adrenergic, estrogen, cytokine, and vascular reactivity
      receptors. RESULTS: Acute E(2) stimulation significantly attenuated catecholamine
      stimulated lipolysis in femoral subcutaneous adipose tissue (interstitial
      glycerol concentration (micromole/liter) ANOVA time vs treatment interaction,
      P=0.01) and lipolysis in general in abdominal adipose tissue (ANOVA treatment
      alone, P<0.05). E(2) also reduced basal lipid oxidation ((mg/kg per min) placebo,
      0.58 +/- 0.06 vs E(2), 0.45 +/- 0.03; P=0.03) and induced a significantly higher
      expression of anti-lipolytic alpha2A-adrenergic receptor mRNA (P=0.02) in
      skeletal muscle tissue as well as an upregulation of eNOS (NOS3) mRNA (P=0.02).
      CONCLUSION: E(2) acutely attenuates the lipolytic response to catecholamines in
      subcutaneous adipose tissue, shifts muscular adrenergic receptor mRNA toward anti
      lipolytic alpha2A-receptors, decreases whole body lipid oxidation, and enhances
      expression of markers of vascular reactivity.

PMID- 22872468
TI  - Different PTH response to oral peptone load and oral calcium load in patients
      with normocalcemic primary hyperparathyroidism, primary hyperparathyroidism, and
      healthy subjects.
AB  - BACKGROUND: Normocalcemic primary hyperparathyroidism (PHPT-N) is a condition
      that may have similar long-term implications to primary hyperparathyroidism
      (PHPT); however, differential diagnosis and treatment for parathyroid disorders
      are not clearly defined. We investigated the effect of an oral peptone and an
      oral calcium load on calcium-regulating hormones in PHPT-N compared with PHPT and
      healthy controls to provide a new potential diagnostic tool. DESIGN: Case-control
      study. METHODS: We evaluated serum gastrin, PTH, ionized calcium, and phosphate
      responses to oral calcium (1 g) and peptone (10 g) load in 22 PHPT and 20 PHPT-N
      patients matched for PTH serum values. Moreover, 30 healthy subjects were
      enrolled as controls. In 12 patients for each group, we also performed the oral
      peptone test adding aluminum hydroxide (AH) to suppress phosphate absorption.
      RESULTS: In PHPT patients, PTH increased significantly 30 min after the oral
      peptone load, while no significant increase was found in PHPT-N and controls.
      After oral calcium load, PTH remained stable in PHPT while it decreased
      dramatically in PHPT-N patients, and ionized calcium increased significantly in
      each of the three groups. Peptones plus AH induced a blunted PTH increase in the
      three groups. CONCLUSIONS: Considering the marked difference in PTH response
      elicited by peptones in PHPT compared with PHPT-N, we suggest that the oral
      peptone test could be added to the diagnostic evaluation of PHPT patients. In
      case of absent response to peptones, patients should have their serum calcium
      levels assessed twice a year in accordance with recent guidelines.

PMID- 22872469
TI  - Digested and fermented green kiwifruit increases human beta-defensin 1 and 2
      production in vitro.
AB  - The intestinal mucosa is constantly exposed to a variety of microbial species
      including commensals and pathogens, the latter leaving the host susceptible to
      infection. Antimicrobial peptides (AMP) are an important part of the first line
      of defense at mucosal surfaces. Human beta-defensins (HBD) are AMP expressed by
      colonic epithelial cells, which act as broad spectrum antimicrobials. This study
      explored the direct and indirect effects of green kiwifruit (KF) on human beta
      defensin 1 and 2 (HBD-1 and 2) production by epithelial cells. In vitro digestion
      of KF pulp consisted of a simulated gastric and duodenal digestion, followed by
      colonic microbial fermentation using nine human faecal donors. Fermenta from
      individual donors was sterile filtered and independently added to epithelial
      cells prior to analysis of HBD protein production. KF products obtained from the
      gastric and duodenal digestion had no effect on the production of HBD-1 or 2 by
      epithelial cells, demonstrating that KF does not contain substances that directly
      modulate defensin production. However, when the digested KF products were further
      subjected to in vitro colonic fermentation, the fermentation products
      significantly up-regulated HBD-1 and 2 production by the same epithelial cells.
      We propose that this effect was predominantly mediated by the presence of short
      chain fatty acids (SCFA) in the fermenta. Exposure of cells to purified SCFA
      confirmed this and HBD-1 and 2 production was up-regulated with acetate,
      propionate and butyrate. In conclusion, in vitro colonic fermentation of green
      kiwifruit digest appears to prime defense mechanisms in gut cells by enhancing
      the production of antimicrobial defensins.

PMID- 22872470
TI  - An SNP in the MyoD1 gene intron 2 associated with growth and carcass traits in
      three duck populations.
AB  - Myogenic differentiation 1 (MyoD1) genes belong to the MyoD gene family and play
      key roles in growth and muscle development. This study was designed to
      investigate the effects of variants in the MyoD1 gene on duck growth and carcass
      traits. Three duck populations (Cherry Valley, Jingjiang, and Muscovy) were
      sampled, their growth and carcass traits were measured, and they were genotyped
      using the PCR-RFLP method. The results showed one novel polymorphism, an
      alteration in intron 2 of the MyoD1 gene (A to T). It was associated with the
      traits of weight at 8 weeks, carcass weight, breast muscle weight, leg muscle
      weight, eviscerated percentage, percentage of leg muscle weight, dressing
      percentage, and lean meat percentage. This alteration in intron 2 of MyoD1 may be
      linked with potential major loci or genes affecting some growth and carcass
      traits.

PMID- 22872471
TI  - Linking continuous and discrete intervertebral disc models through
      homogenisation.
AB  - At present, there are two main numerical approaches that are frequently used to
      simulate the mechanical behaviour of the human spine. Researchers with a
      continuum-mechanical background often utilise the finite-element method (FEM),
      where the involved biological soft and hard tissues are modelled on a macroscopic
      (continuum) level. In contrast, groups associated with the science of human
      movement usually apply discrete multi-body systems (MBS). Herein, the bones are
      modelled as rigid bodies, which are connected by Hill-type muscles and non-linear
      rheological spring-dashpot models to represent tendons and cartilaginous
      connective tissue like intervertebral discs (IVD). A possibility to benefit from
      both numerical methods is to couple them and use each approach, where it is most
      appropriate. Herein, the basic idea is to utilise MBS in simulations of the
      overall body and apply the FEM only to selected regions of interest. In turn, the
      FEM is used as homogenisation tool, which delivers more accurate non-linear
      relationships describing the behaviour of the IVD in the multi-body dynamics
      model. The goal of this contribution is to present an approach to couple both
      numerical methods without the necessity to apply a gluing algorithm in the
      context of a co-simulation. Instead, several pre-computations of the
      intervertebral disc are performed offline to generate an approximation of the
      homogenised finite-element (FE) result. In particular, the discrete degrees of
      freedom (DOF) of the MBS, that is, three displacements and three rotations, are
      applied to the FE model of the IVD, and the resulting homogenised forces and
      moments are recorded. Moreover, a polynomial function is presented with the
      discrete DOF of the MBS as variables and the discrete forces an moments as
      function values. For the sake of a simple verification, the coupling method is
      applied to a simplified motion segment of the spine. Herein, two stiff
      cylindrical vertebrae with an interjacent homogeneous cylindrical IVD are
      examined under the restriction of purely elastic deformations in the sagittal
      plane.

PMID- 22872472
TI  - Introduction to germ cell development in Caenorhabditis elegans.
AB  - A central feature of the continuum of life in sexually reproducing metazoans is
      the cycle of the germline from one generation to the next. This volume describes
      the cycle of the germline for Caenorhabditis elegans through chapters that are
      focused on distinct aspects or processes in germ cell development. Topics include
      sequential and dependent processes such as specification of germ cells as
      distinct from somatic cells, sex determination, stem cell proliferative fate
      versus meiotic development decision, recombination/progression through meiotic
      prophase, contemporaneous processes such as gametogenesis, meiotic development
      and apoptosis, and continuing the cycle into the next generation through
      fertilization and the oocyte-to-embryo transition. Throughout germ cell
      development, translational control and epigenetic mechanisms play prominent
      roles. These different aspects of germ cell development are seamlessly integrated
      under optimal conditions and are modified in the different reproductive
      strategies that are employed by C. elegans under harsh environmental conditions.
      In this chapter, we set the stage by providing a brief background on the C.
      elegans system and germ cell development, indicating processes in the cycle of
      the germline that are covered in each chapter.

PMID- 22872474
TI  - Sex determination in the Caenorhabditis elegans germline.
AB  - How is sex determined? In the animal kingdom, there are diverse sets of
      mechanisms for determining organismal sex, with the predominant ones being
      chromosomally based, either a dominant-acting sex chromosome or the ratio of the
      number of X chromosome to autosomes, which lead to oocyte-producing females and
      sperm-producing males. The resulting germline sexual phenotype is often the
      logical consequence of somatic sex determination. In this respect however, the
      Caenorhabditis elegans hermaphrodite is different from mammals and Drosophila. In
      fact in the C. elegans hermaphrodite germline, male gametes are transiently
      produced in a female body during larval development. To override chromosomal
      signals, sex determination of germ cells strongly depends on post-transcriptional
      regulation. A pivotal role for male gamete production (spermatogenesis) is played
      by the fem-3 mRNA, which is controlled through FBF and other RNA-binding proteins
      or splicing factors. Thanks to its powerful genetics, transparent body, small
      size, and the ability to make sperm and oocytes within one individual, C. elegans
      represents an excellent system to investigate cellular differentiation and post
      transcriptional control.

PMID- 22872473
TI  - Germ cell specification.
AB  - The germline of Caenorhabditis elegans derives from a single founder cell, the
      germline blastomere P(4). P(4) is the product of four asymmetric cleavages that
      divide the zygote into distinct somatic and germline (P) lineages. P(4) inherits
      a specialized cytoplasm ("germ plasm") containing maternally encoded proteins and
      RNAs. The germ plasm has been hypothesized to specify germ cell fate, but the
      mechanisms involved remain unclear. Three processes stand out: (1) inhibition of
      mRNA transcription to prevent activation of somatic development, (2)
      translational regulation of the nanos homolog nos-2 and of other germ plasm
      mRNAs, and (3) establishment of a unique, partially repressive chromatin.
      Together, these processes ensure that the daughters of P(4), the primordial germ
      cells Z2 and Z3, gastrulate inside the embryo, associate with the somatic gonad,
      initiate the germline transcriptional program, and proliferate during larval
      development to generate ~2,000 germ cells by adulthood.

PMID- 22872475
TI  - Stem cell proliferation versus meiotic fate decision in Caenorhabditis elegans.
AB  - The C. elegans germ line has emerged as an important model for -understanding how
      a stem cell population is maintained throughout the life of the animal while
      still producing the gametes necessary for propagation of the species. The stem
      cell population in the adult hermaphrodite is relatively large, with stem cells
      giving rise to daughters that appear intrinsically equivalent; however, some of
      the daughters retain the proliferative fate while others enter meiotic prophase.
      While machinery exists for cells to progress through the mitotic cell cycle and
      machinery exists for cells to progress through meiotic prophase, central to
      understanding germ line development is identifying the genes and regulatory
      processes that determine whether the mitotic cell cycle or meiotic prophase
      machinery will be utilized; in other words, the genes that regulate the switch of
      germ cells from the proliferative stem cell fate to the meiotic development fate.
      Whether a germ cell self-renews or enters meiotic prophase is largely determined
      by its proximity to the distal tip cell (DTC), which is the somatic niche cell
      that caps the distal end of the gonad. Germ cells close to the DTC have high
      levels of GLP-1 Notch signaling, which promotes the proliferative fate, while
      cells further from the DTC have high activity levels of the GLD-1 and GLD-2
      redundant RNA regulatory pathways, as well as a third uncharacterized pathway,
      each of which direct cells to enter meiotic prophase. Other factors and pathways
      modulate this core genetic pathway, or work in parallel to it, presumably to
      ensure that a tight balance is maintained between proliferation and meiotic
      entry.

PMID- 22872476
TI  - Physiological control of germline development.
AB  - The intersection between developmental programs and environmental conditions that
      alter physiology is a growing area of research interest. The C. elegans germ line
      is emerging as a particularly sensitive and powerful model for these studies. The
      germ line is subject to environmentally regulated diapause points that allow
      worms to withstand harsh conditions both prior to and after reproduction
      commences. It also responds to more subtle changes in physiological conditions.
      Recent studies demonstrate that different aspects of germ line development are
      sensitive to environmental and physiological changes and that conserved signaling
      pathways such as the AMPK, Insulin/IGF, TGFbeta, and TOR-S6K, and nuclear hormone
      receptor pathways mediate this sensitivity. Some of these pathways genetically
      interact with but appear distinct from previously characterized mechanisms of
      germline cell fate control such as Notch signaling. Here, we review several
      aspects of hermaphrodite germline development in the context of "feasting," "food
      limited," and "fasting" conditions. We also consider connections between
      lifespan, metabolism and the germ line, and we comment on special considerations
      for examining germline development under altered environmental and physiological
      conditions. Finally, we summarize the major outstanding questions in the field.

PMID- 22872478
TI  - Spermatogenesis.
AB  - During spermatogenesis, pluripotent germ cells differentiate to become efficient
      delivery vehicles to the oocyte of paternal DNA. Though male and female germ
      cells both undergo meiosis to produce haploid complements of DNA, at the same
      time they also each undergo distinct differentiation processes that result in
      either sperm or oocytes. This review will discuss our current understanding of
      mechanisms of sperm formation and differentiation in Caenorhabditis elegans
      gained from studies that employ a combination of molecular, transcriptomic, and
      cell biological approaches. Many of these processes also occur during
      spermatogenesis in other organisms but with differences in timing, molecular
      machinery, and morphology. In C. elegans, sperm differentiation is implemented by
      varied modes of gene regulation, including the genomic organization of genes
      important for sperm formation, the generation of sperm-specific small RNAs, and
      the interplay of specific transcriptional activators. As sperm formation
      progresses, chromatin is -systematically remodeled to allow first for the
      implementation of differentiation programs, then for sperm-specific DNA packaging
      required for transit of paternal genetic and epigenetic information. Sperm also
      exhibit distinctive features of -meiotic progression, including the formation of
      a unique karyosome state and the centrosomal-based segregation of chromosomes
      during symmetric meiotic -divisions. Sperm-specific organelles are also assembled
      and remodeled as cells complete -meiosis and individualize in preparation for
      activation, morphogenesis, and the acquisition of motility. Finally, in addition
      to DNA, sperm contribute specific cellular factors that contribute to successful
      embryogenesis.

PMID- 22872479
TI  - Translational control in the Caenorhabditis elegans germ line.
AB  - Translational control is a prevalent form of gene expression regulation in the
      Caenorhabditis elegans germ line. Linking the amount of protein synthesis to mRNA
      quantity and translational accessibility in the cell cytoplasm provides unique
      advantages over DNA-based controls for developing germ cells. This mode of gene
      expression is especially exploited in germ cell fate decisions and during
      oogenesis, when the developing oocytes stockpile hundreds of different mRNAs
      required for early embryogenesis. Consequently, a dense web of RNA regulators,
      consisting of diverse RNA-binding proteins and RNA-modifying enzymes, control the
      translatability of entire mRNA expression programs. These RNA regulatory networks
      are tightly coupled to germ cell developmental progression and are themselves
      under translational control. The underlying molecular mechanisms and RNA codes
      embedded in the mRNA molecules are beginning to be understood. Hence, the C.
      elegans germ line offers fertile grounds for discovering post-transcriptional
      mRNA regulatory mechanisms and emerges as great model for a systems level
      understanding of translational control during development.

PMID- 22872477
TI  - Meiotic development in Caenorhabditis elegans.
AB  - Caenorhabditis elegans has become a powerful experimental organism with which to
      study meiotic processes that promote the accurate segregation of chromosomes
      during the generation of haploid gametes. Haploid reproductive cells are produced
      through one round of chromosome replication followed by two -successive cell
      divisions. Characteristic meiotic chromosome structure and dynamics are largely
      conserved in C. elegans. Chromosomes adopt a meiosis-specific structure by
      loading cohesin proteins, assembling axial elements, and acquiring chromatin
      marks. Homologous chromosomes pair and form physical connections though synapsis
      and recombination. Synaptonemal complex and crossover formation allow for the
      homologs to stably associate prior to remodeling that facilitates their
      segregation. This chapter will cover conserved meiotic processes as well as
      highlight aspects of meiosis that are unique to C. elegans.

PMID- 22872480
TI  - Germ cell apoptosis and DNA damage responses.
AB  - In the past 12 years, since the first description of C. elegans germ cell
      apoptosis, this area of research rapidly expanded. It became evident that
      multiple genetic pathways lead to the apoptotic demise of germ cells. We are only
      beginning to understand how these pathways that all require the CED-9/Bcl-2, Apaf
      1/CED-4 and CED-3 caspase core apoptosis components are regulated. Physiological
      apoptosis, which likely accounts for the elimination of more than 50% of all germ
      cells, even in unperturbed conditions, is likely to be required to maintain
      tissue homeostasis. The best-studied pathways lead to DNA damage-induced germ
      cell apoptosis in response to a variety of genotoxic stimuli. This apoptosis
      appears to be regulated similar to DNA damage-induced apoptosis in the mouse germ
      line and converges on p53 family transcription factors. DNA damage response
      pathways not only lead to apoptosis induction, but also directly affect DNA
      repair, and a transient cell cycle arrest of mitotic germ cells. Finally,
      distinct pathways activate germ cell apoptosis in response to defects in meiotic
      recombination and meiotic chromosome pairing.

PMID- 22872482
TI  - Fertilization.
AB  - Fertilization-the fusion of gametes to produce a new organism-is the culmination
      of a multitude of intricately regulated cellular processes. In Caenorhabditis
      elegans, fertilization is highly efficient. Sperm become fertilization competent
      after undergoing a maturation process during which they become motile, and the
      plasma membrane protein composition is reorganized in preparation for interaction
      with the oocyte. The highly specialized gametes begin their interactions by
      signaling to one another to ensure that fertilization occurs when they meet. The
      oocyte releases prostaglandin signals to help guide the sperm to the site of
      fertilization, and sperm secrete a protein called major sperm protein (MSP) to
      trigger oocyte maturation and ovulation. Upon meeting one another in the
      spermatheca, the sperm and oocyte fuse in a specific and tightly regulated
      process. Recent studies are providing new insights into the molecular basis of
      this fusion process. After fertilization, the oocyte must quickly transition from
      the relative quiescence of oogenesis to a phase of rapid development during the
      cleavage divisions of early embryogenesis. In addition, the fertilized oocyte
      must prevent other sperm from fusing with it as well as produce an eggshell for
      protection during external development. This chapter will review the nature and
      regulation of the various cellular processes of fertilization, including the
      development of fertilization competence, gamete signaling, sperm-oocyte fusion,
      the oocyte to embryo transition, and production of an eggshell to protect the
      developing embryo.

PMID- 22872483
TI  - The oocyte-to-embryo transition.
AB  - The oocyte-to-embryo transition refers to the process whereby a fully grown,
      relatively quiescent oocyte undergoes maturation, fertilization, and is converted
      into a developmentally active, mitotically dividing embryo, arguably one of the
      most dramatic transitions in biology. This transition occurs very rapidly in
      Caenorhabditis elegans, with fertilization of a new oocyte occurring every 23 min
      and the first mitotic division occurring 45 min later. Molecular events
      regulating this transition must be very precisely timed. This chapter reviews our
      current understanding of the coordinated temporal regulation of different events
      during this transition. We divide the oocyte-to-embryo transition into a number
      of component processes, which are coordinated primarily through the MBK-2 kinase,
      whose activation is intimately tied to completion of meiosis, and the OMA-1/OMA-2
      proteins, whose expression and functions span multiple processes during this
      transition. The oocyte-to-embryo transition occurs in the absence of de novo
      transcription, and all the factors required for the process, whether mRNA or
      protein, are already present within the oocyte. Therefore, all regulation of this
      transition is posttranscriptional. The combination of asymmetric partitioning of
      maternal factors, protein modification-mediated functional switching, protein
      degradation, and highly regulated translational repression ensure a smooth oocyte
      to-embryo transition. We will highlight protein degradation and translational
      repression, two posttranscriptional processes which play particularly critical
      roles in this transition.

PMID- 22872484
TI  - Epigenetic control of germline development.
AB  - Dynamic regulation of histone modifications and small noncoding RNAs is observed
      throughout the development of the C. elegans germ line. Histone modifications are
      differentially regulated in the mitotic vs meiotic germ line, on X chromosomes vs
      autosomes and on paired chromosomes vs unpaired chromosomes. Small RNAs function
      in transposon silencing and developmental gene regulation. Histone modifications
      and small RNAs produced in the germ line can be inherited and impact embryonic
      development. Disruption of histone-modifying enzymes or small RNA machinery in
      the germ line can result in sterility due to degeneration of the germ line and/or
      an inability to produce functional gametes.

PMID- 22872485
TI  - Using Caenorhabditis to explore the evolution of the germ line.
AB  - Germ cells share core attributes and homologous molecular components across
      animal phyla. Nevertheless, abrupt shifts in reproductive mode often occur that
      are mediated by the rapid evolution of germ cell properties. Studies of
      Caenorhabditis nematodes show how the otherwise conserved RNA-binding proteins
      (RBPs) that regulate germline development and differentiation can undergo
      surprisingly rapid functional evolution. This occurs even as the narrow
      biochemical tasks performed by the RBPs remain constant. The biological roles of
      germline RBPs are thus highly context-dependent, and the inference of archetypal
      roles from isolated models in different phyla may therefore be premature.

PMID- 22872486
TI  - Association of miR-146aC>G, miR-196a2T>C, and miR-499A>G polymorphisms with risk
      of premature ovarian failure in Korean women.
AB  - We investigated whether microRNA (miRNA) polymorphisms (miR-146aC>G, miR
      196a2T>C, and miR-499A>G) confer risk of premature ovarian failure (POF) in
      Korean women. DNA samples from 136 patients with POF and 234 controls were
      genotyped for the 3 miRNA single-nucleotide polymorphisms by polymerase chain
      reaction-restriction fragment length polymorphism. The miR-146aCG/miR-196a2TC
      combined genotype was less frequent in patients than in controls (P < .05),
      conferring less susceptibility. Using haplotype-based multifactor dimensionality
      reduction analysis, the C-C-A and G-T-A inferred haplotypes (miR-146a/miR
      196a2/miR-499) were less frequent in patients, suggesting protective effects (P <
      .05 for each), whereas the C-T-A and G-C-A haplotypes were more frequent in
      patients (P < .05 for each). The C-T and G-C haplotypes (miR-146a/miR-196a2) were
      more frequent in patients, whereas the C-C and G-T haplotypes were less frequent
      in patients (P < .05 for each). However, none of the 3 miRNA polymorphisms alone
      was associated with POF risk. Our findings suggest that putative gene-gene
      interaction between miR-146 and miR-196a2 may be involved in POF development.

PMID- 22872481
TI  - Control of oocyte growth and meiotic maturation in Caenorhabditis elegans.
AB  - In sexually reproducing animals, oocytes arrest at diplotene or diakinesis and
      resume meiosis (meiotic maturation) in response to hormones. Chromosome
      segregation errors in female meiosis I are the leading cause of human birth
      defects, and age-related changes in the hormonal environment of the ovary are a
      suggested cause. Caenorhabditis elegans is emerging as a genetic paradigm for
      studying hormonal control of meiotic maturation. The meiotic maturation processes
      in C. elegans and mammals share a number of biological and molecular
      similarities. Major sperm protein (MSP) and luteinizing hormone (LH), though
      unrelated in sequence, both trigger meiotic resumption using somatic Galpha(s)
      adenylate cyclase pathways and soma-germline gap-junctional communication. At a
      molecular level, the oocyte responses apparently involve the control of conserved
      protein kinase pathways and post-transcriptional gene regulation in the oocyte.
      At a cellular level, the responses include cortical cytoskeletal rearrangement,
      nuclear envelope breakdown, assembly of the acentriolar meiotic spindle,
      chromosome segregation, and likely changes important for fertilization and the
      oocyte-to-embryo transition. This chapter focuses on signaling mechanisms
      required for oocyte growth and meiotic maturation in C. elegans and discusses how
      these mechanisms coordinate the completion of meiosis and the oocyte-to-embryo
      transition.

PMID- 22872487
TI  - Expression and localization of aquaporins 8 and 9 in term placenta with
      oligohydramnios.
AB  - To test the expression and localization of aquaporins 8 (AQP8) and 9 (AQP9) in
      human term fetal membranes and placenta in both oligohydramnios and normal
      amniotic fluid volume (AFV) groups and to explore the association between
      aquaporin expression and oligohydramnios. Real-time polymerase chain reaction and
      immunohistochemistry were used to determine AQP8 and AQP9 expression levels and
      localization in amnion, chorion, and placenta, respectively. In addition,
      compared with the normal AFV group, the expression levels of both AQP8 and AQP9
      in amnion in oligohydramnios group were significantly decreased, while their
      expressions in placenta were significantly increased. The expression level of
      AQP9 was also significantly decreased in chorion, while that of AQP8 was
      unchanged. Both AQP8 and AQP9 may play an important role in water flow both in
      intramembranous absorption and in placental water transfer. Our study offers the
      potential therapeutic approach for oligohydramnios.

PMID- 22872488
TI  - WNT/beta-catenin-signaling pathway stimulates the proliferation of cultured adult
      human Sertoli cells via upregulation of C-myc expression.
AB  - The role of WNT/beta-catenin-signaling pathway is critical in mouse Sertoli cell
      maturation and tumorigenesis. This study aims to examine the effects of WNT/beta
      catenin signaling on the cultured adult human Sertoli cells and the underlying
      molecular mechanisms. Glycogen synthase kinase 3beta (GSK-3beta) inhibitors,
      SB216763 and lithium chloride (LiCl), were used to activate WNT/beta-catenin
      signaling pathway. 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay and flow
      cytometry were used to analyze the proliferation and cell cycle of cultured human
      Sertoli cells, respectively. C-myc expression was accessed by immunofluorescence,
      real-time polymerase chain reaction and Western blot. The effects of c-myc on
      Sertoli cell proliferation were investigated by RNA interference technology and
      BrdU incorporation assay. The results showed activation of WNT/beta-catenin
      signaling stimulated human Sertoli cell proliferation. Obvious increases in c-myc
      messenger RNA and protein expression were observed after SB216763 and LiCl
      treatments. Knockdown of c-myc expression attenuated the ability of WNT/beta
      catenin signaling to stimulate the proliferation of human Sertoli cells. WNT/beta
      catenin signaling enhances human Sertoli cell proliferation via upregulation of c
      myc expression.

PMID- 22872489
TI  - Expression profile of extracellular matrix and adhesion molecules in the
      development of endometriosis in a mouse model.
AB  - Ectopic endometrial tissue induces various reactions in surrounding tissues, such
      as the surface of the ovary and peritoneal cavity, leading to endometriosis. The
      aim of this study is to investigate the expression profile of extracellular
      matrix (ECM) and adhesion molecules in the early steps of development of
      experimental mouse endometriosis, specifically in peritoneum adjacent to
      endometrium transplants attached via autotransplantation. The endometriosis model
      was induced by autotransplantation of endometrium to peritoneal tissue.
      Peritoneal tissues adjacent to the transplant were obtained at 1, 4, and 7 days
      posttransplantation. The results showed that messenger RNA expression levels of
      most of the integrins, collagens, and other ECM reached a peak at 7 days
      posttransplantation. Uniquely, Lamc2 was significantly increased to its maximum
      level within 24 hours posttransplantation and may be strongly associated with
      initiation of the development of endometriosis. These data will be helpful in
      further investigations of the treatment of endometriosis.

PMID- 22872490
TI  - Isoform alpha of PKC may contribute to the maintenance of pregnancy myometrial
      quiescence in humans.
AB  - We postulate that protein kinase C alpha (PKCalpha) may contribute to the
      maintenance of pregnancy myometrial quiescence in humans. We studied the changes
      in myometrial PKCalpha gene products (messenger RNA [mRNA] and protein) in 4
      groups of women: preterm not in labor (PT-NL), preterm in labor (PT-L), term not
      in labor (T-NL), and term in labor (T-L). The degree of PKCalpha activation was
      studied by comparing the levels of particulate (active) PKCalpha with the total
      PKCalpha protein levels and by measuring PKCalpha activity in the cytosolic and
      particulate fractions. Protein kinase Calpha abundance (mRNA and protein) did not
      increase during myometrial quiescence (PT-NL), whereas the level of PKCalpha
      activity significantly increased during quiescence. The activity of PKCalpha
      significantly decreased in the T-NL, T-L, and PT-L groups. These findings suggest
      that PKCalpha plays a significant role in the maintenance of myometrial
      quiescence and that PKCalpha activity must decrease at the end of pregnancy
      allowing myometrial activation. Additionally, our data demonstrate an association
      between reduced PKCalpha activity and preterm labor, which merits further
      investigation.

PMID- 22872491
TI  - Conus medullaris metastasis in breast cancer: report of a case and a review of
      the literature.
AB  - Intramedullary spinal cord metastasis is quite rare. This report presents the
      case of a female patient with metastasis of the conus medullaris from breast
      cancer, presenting with paraplegia and sphincter dysfunction. Bladder dysfunction
      improved after removal of the conus mass. This report is the seventh case of
      conus medullaris metastasis from breast cancer and the first review of clinical
      outcome, survival time and other data of all these 7 cases. This study also
      reviewed cases of intramedullary spinal cord metastasis arising from breast
      cancer in regions other than the conus medullaris in the literature. Longer
      survival time resulted from surgery in contrast to those without surgery in the
      latter group. 

PMID- 22872492
TI  - Integrating substance use treatment into adolescent health care.
AB  - Substance use (SU) problems are common among adolescents, a serious health risk
      for them and a major public health problem, but are inadequately addressed in
      most pediatric health care settings. Primary care offers an excellent context for
      SU assessment and treatment for adolescents and their families, offering better
      access and a less stigmatized environment for receiving treatment than specialty
      programs. This paper examines the literature on the integration of substance use
      treatment with adolescent health care, focusing on 2 areas: Screening, Brief
      Intervention, and Referral to Treatment (SBIRT) in Emergency Departments and
      Primary Care, and School- and College-Based Health Centers.

PMID- 22872493
TI  - Obstructive sleep apnea and severe mental illness: evolution and consequences.
AB  - Sleep complaints are commonly encountered in psychiatric clinics. Underlying
      medical disorders or sleep disorders need to be identified and treated to
      optimize treatment of the mental illness. Excessive daytime sleepiness, which is
      the main symptom of obstructive sleep apnea (OSA), overlaps with those of many
      severe mental illnesses. Medication side effects or the disorder itself maybe
      account for daytime sleepiness but comorbid OSA is a possibility that should not
      be overlooked. The diagnosis of OSA is straightforward but treatment compliance
      is problematic in psychiatric patients. This article summarizes studies
      concerning comorbid OSA in patients with severe mental illness and includes
      suggestions for future investigations.

PMID- 22872494
TI  - Pollution biomarkers in the spiny lizard (Sceloporus spp.) from two suburban
      populations of Monterrey, Mexico.
AB  - Environmental pollution may severely impact reptile species in urbanized areas.
      The magnitude of the impact is analyzed in the present study using lizard tail
      tips for the quantitative evaluation of enzymatic biomarkers of pollution. Spiny
      lizards (Sceloporus serrifer and S. torquatus) were collected from two suburban
      localities in the Monterrey metropolitan area, Mexico: Chipinque Ecological Park,
      a natural protected area, and El Carmen Industrial Park (IP), a highly polluted
      site. Different enzymes were used as biomarkers including: acetylcholinesterase
      (AChE), butyrylcholinesterase (BChE), carboxylesterase (CaE), alkaline
      phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD) and
      glutathione S-transferase (GST). The levels of AChE, BChE and ACP activity were
      not significantly different between localities. AChE and BChE, commonly used as
      biomarkers of neurotoxic polluting agents (e.g. organophosphate pesticides) do
      not appear to be affecting the populations from the study locations. In contrast,
      the levels of CaE, GST, ALP and SOD were significantly different between the
      localities. These biomarkers are regularly associated with oxidative stress and
      processes of detoxification, and generally indicate pollution caused by heavy
      metals or hydrocarbons, which are common in industrial sites. The data resulting
      from the analysis of these biomarkers indicate that these polluting agents are
      affecting the populations of Sceloporus in IP. The present work validates the
      possibility of conducting additional ecotoxicological studies using biomarkers in
      combination with a nondestructive sampling technique in species of spiny lizards
      that are abundant in many North America areas.

PMID- 22872495
TI  - Recurrent amebic liver abscess.
AB  - Recurrence of amebic liver abscess is uncommon. We report a 62-year-old man
      presenting with amebic liver abscess thrice in last 5 years.

PMID- 22872496
TI  - Overexpression of CsANR increased flavan-3-ols and decreased anthocyanins in
      transgenic tobacco.
AB  - Anthocyanins and flavan-3-ols are distributed widely in plants and synthesized by
      a common biosynthetic pathway. Anthocyanin reductase (ANR) represents branching
      point enzyme of this pathway converting anthocyanidins to flavan-3-ols. Since tea
      contains highest amount of flavonoids, a cDNA encoding anthocyanin reductase from
      tea (CsANR) was overexpressed in transgenic tobacco to check the influence on
      anthocyanin and flavan-3-ols. The transgenic tobacco was confirmed by genomic PCR
      and expression of transgene was analyzed through semiquantitative PCR.
      Interestingly flowers of transgenic tobacco were light pink/white in color
      instead of dark pink in wild tobacco, documenting the decrease in anthocyanins
      content. Upon measurement, flower anthocyanin content was found to be lesser.
      While flavan-3-ols (epicatechin and epigallocatechin) contents were increased in
      leaf tissue of transgenic lines. The expressions of other endogenous flavonoid
      biosynthetic pathway genes in different floral parts (sepal, petal, stamen, and
      carpel) of CsANR overexpressing tobacco as well as wild tobacco were analyzed.
      The transcript levels of PAL and CHI genes were downregulated, while transcript
      levels of F3H, FLS, CHS, ANR1, and ANR2 genes were upregulated in all floral
      parts of CsANR transgenic plants compared to wild tobacco. The expressions of DFR
      and ANS genes were also spatially modulated in different floral parts due to
      overexpression of CsANR. Thus, CsANR overexpression increased flavan-3-ols and
      decreased anthocyanin content by modulating the expressions of various flavonoid
      biosynthetic pathway genes in flower of tobacco. These changes might be
      responsible for the observed pollen tube in the pollens of CsANR overexpressing
      transgenic tobacco when they were still in the anther before pollination.

PMID- 22872497
TI  - Studies on the refolding process of recombinant horseradish peroxidase.
AB  - Horseradish peroxidase (HRP) is an important heme-containing glyco-enzyme that
      has been used in many biotechnological fields. Valuable proteins like HRP can be
      obtained in sufficient amounts using Escherichia coli as an expression system.
      However, frequently, the expression of recombinant enzyme results in inclusion
      bodies, and the refolding yield is generally low for proteins such as plant
      peroxidases. In this study, a recombinant HRP was cloned and expressed in the
      form of inclusion bodies. Initially, the influence of few additives on HRP
      refolding was assessed by the one factor at a time method. Subsequently, factors
      with significant effects including glycerol, GSSG/DTT, and the enzyme
      concentration were selected for further optimization by means of the central
      composite design of response surface methodology (RSM). Under the obtained
      optimal condition, refolding increased about twofold. The refolding process was
      then monitored by the intrinsic fluorescence intensity under optimal conditions
      (0.35 mM GSSG, 0.044 mM DTT, 7 % glycerol, 1.7 M urea, and 2 mM CaCl2 in 20 mM
      Tris, pH 8.5) and the reconstitution of heme to the refolded peroxidase was
      detected by the Soret absorbance. Additionally, samples under unfolding and
      refolding conditions were analyzed by Zetasizer to determine size distribution in
      different media.

PMID- 22872498
TI  - Isolation of an extremely acidophilic and highly efficient strain
      Acidithiobacillus sp. for chalcopyrite bioleaching.
AB  - An extremely acidophilic sulfur-oxidizing bacterium was isolated from an
      industrial-scale bioheap of the Zijinshan copper mine and was named ZJJN. A tuft
      of flagella and a layer of thick capsule outside the cell envelope were clearly
      observed under transmission electron microscopy (TEM), which might be closely
      related to the extremely acid-proof capacity of ZJJN cells in the bioleaching
      system; 16S ribosomal RNA (rRNA) phylogeny showed that the isolated strain was
      highly homologous to the genera of Acidithiobacillus. The optimum temperature of
      ZJJN was determined at 30  degrees C and pH at 1.0. It was capable of growth at
      even pH 0. Strain ZJJN can utilize reduced sulfur as an energy source but not
      with organics or ferrous ion. Strain ZJJN was sensitive to all antibiotics with
      different concentrations; when it showed a certain resistance to different
      concentrations of Cu(2+). In the mixed strains of ZJJN and A. ferrooxidans system
      (initial pH 1.0), the copper-leaching efficiency was up to 60.1 %, which was far
      higher than other systems. Scanning electron microscopy (SEM) analysis showed
      that less jarosite precipitation was produced in the most efficient system. The
      extremely acidophilic strain ZJJN would be of great potential in the application
      of chalcopyrite bioleaching.

PMID- 22872499
TI  - Ten-year change in self-rated quality of life in a type 1 diabetes population:
      Wisconsin Epidemiologic Study of Diabetic Retinopathy.
AB  - PURPOSE: To investigate a 10-year change of quality of life and associated
      factors in a population with type 1 diabetes. METHODS: The Medical Outcome Study
      Short Form-36 (SF-36) was administered in participants (n = 520) at the 1995-1996
      and 2005-2007 examination phases of the Wisconsin Epidemiologic Study of Diabetic
      Retinopathy (WESDR). Physical (PCS) and mental (MCS) component summary scores
      were calculated. The associations between changes of quality of life and
      demographic, socioeconomic, and clinical factors were analyzed. RESULTS: PCS
      score decreased (p < 0.001) and MCS score increased (p < 0.001) after 10 years.
      The development of cardiovascular disease and the presence of limb amputation
      were associated with decrease in the PCS score. Those who were working and
      retired had increased MCS; those who were working and stopped had a decrease in
      the MCS score. Change in visual acuity and diabetic retinopathy status did not
      have a significant impact in health-related quality of life scores. CONCLUSIONS:
      Our findings reinforce the necessity to make every attempt to decrease
      complications of diabetes in individuals with long-term type 1 diabetes in order
      to attenuate the diminished quality of life associated with those complications
      such as cardiovascular disease. Change in employment status, likely due to
      development of these complications, was also strongly associated with poorer
      quality of life and suggests the benefits of preventing or decreasing
      complications to keep people with type 1 diabetes in the workforce.

PMID- 22872500
TI  - Evaluation and management of outlet obstruction in women without anatomical
      abnormalities on physical exam or cystoscopy.
AB  - Bladder outlet obstruction (BOO) in women can be either anatomic or functional.
      Anatomic causes for BOO are often readily apparent by history and physical exam.
      On the other hand, causes for functional obstruction, including dysfunctional
      voiding, primary bladder neck obstruction, and detrusor-external sphincter
      dyssynergia, are more difficult to establish. Because the appropriate treatment
      for functional obstruction drastically varies according to etiology, making an
      accurate diagnosis is paramount. Videourodynamics, interpreted in the context of
      individual clinical symptoms, remains the diagnostic gold standard in women with
      functional obstruction.

PMID- 22872501
TI  - 3T-MRI, elastography, digital mammography, and FDG-PET CT findings of
      subcutaneous panniculitis-like T-cell lymphoma (SPTCL) of the breast.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of
      cutaneous lymphoma, which is characterized by infiltration of neoplastic
      cytotoxic T cells into the subcutaneous tissue. We here report the case of a 66
      year-old woman with SPTCL of the breast, which is a very uncommon location.
      Multiple suspicious irregular small masses in the subcutaneous fat were detected
      by mammography, and sonograms revealed hyperechoic masses. Elastography was
      useful to improve depiction and delineation of SPTCL in the hyperechoic
      subcutaneous fat, and dynamic contrast-enhanced MRI examinations showed multiple
      irregular rim enhanced masses with persistent enhancement. FDG-PET CT images
      showed hypermetabolism in areas corresponding to other imaging techniques. MRI
      can be useful for diagnosis of fat necrosis, which is a primary radiologic
      feature of SPTCL. However, fat necrosis has multitude of appearances by various
      imaging techniques, which typically indicate a benign disease, but may indicate a
      malignancy. Therefore, an ultrasonographically guided core needle biopsy is
      useful for a diagnosis of SPTCL of the breast. The presence of multiple
      subcutaneous nodules throughout the body on CT imaging may be an important
      finding that suggests a diagnosis of SPTCL.

PMID- 22872502
TI  - Clusterin polymorphisms and Alzheimer's disease.

PMID- 22872503
TI  - Generalizability of results from the National Lung Screening Trial.
AB  - Lung cancer is the major cause of cancer-related death worldwide, with a 5-year
      survival of only 16%. Most lung cancer cases are diagnosed at an advanced
      incurable stage. As earlier stages have a better prognosis, the key to reducing
      mortality could be early diagnosis of the disease. At present, low-dose computed
      tomographic (CT) screening has shown promising data. Lung cancer death rates were
      reduced by 20% when CT screening is compared to chest radiography in a high-risk
      group. There are many advantages of CT screening in lung cancer, however there
      are also some important issues that should be taken into account. Therefore, the
      applicability of the results to clinical practice is not clear yet. In this
      Commentary we discuss different aspects that play important roles in the balance
      between harms and benefits of screening, including overdiagnosis, availability of
      treatment options worldwide, ethical considerations, costs, and prolonged life
      expectancy. We conclude that clinicians should be cautious in generalizing
      findings to the total population of smokers and take into account that the use of
      lung cancer screening in clinical practice may have limitations.

PMID- 22872505
TI  - Biomineralization: a proposed evolutionary origin for inorganic cofactors of
      enzymes.
AB  - In this paper, three different reactions of nanoparticles and proteins are
      explained. As a model system, the interactions of birnessite, which is a common
      manganese oxide in the environment, and bovine serum albumin, as a protein that
      has a strong affinity for a variety of inorganic molecules, are studied. The
      author proposes that the cofactor-formation in particular enzymes may be
      considered as a biomineralization in the presence of the protein. One of the
      numerous and very small nanoparticles produced in the presence of protein could
      be formed in an appropriate location in proteins and be used as a primitive
      inorganic core (cofactor) of enzyme.

PMID- 22872506
TI  - Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent
      among samples.
AB  - Measures of RNA abundance are important for many areas of biology and often
      obtained from high-throughput RNA sequencing methods such as Illumina sequence
      data. These measures need to be normalized to remove technical biases inherent in
      the sequencing approach, most notably the length of the RNA species and the
      sequencing depth of a sample. These biases are corrected in the widely used reads
      per kilobase per million reads (RPKM) measure. Here, we argue that the intended
      meaning of RPKM is a measure of relative molar RNA concentration (rmc) and show
      that for each set of transcripts the average rmc is a constant, namely the
      inverse of the number of transcripts mapped. Further, we show that RPKM does not
      respect this invariance property and thus cannot be an accurate measure of rmc.
      We propose a slight modification of RPKM that eliminates this inconsistency and
      call it TPM for transcripts per million. TPM respects the average invariance and
      eliminates statistical biases inherent in the RPKM measure.

PMID- 22872507
TI  - Endovascular stenting for atherosclerotic subclavian artery stenosis in patients
      with other craniocervical artery stenosis.
AB  - Atherosclerotic subclavian artery stenosis (SAS) accompanied with other
      craniocervical artery stenosis (OCAS) is not uncommon in practice. We sought to
      investigate the safety and efficacy of endovascular stenting for SAS in patients
      with OCAS. Between January 2004 and February 2012, 71 consecutive atherosclerotic
      SAS patients who underwent primary stenting in our medical center were included.
      The enrolled patients were divided into combined-SAS group (n = 51) and solitary
      SAS group (n = 20) depending on the presence or absence of OCAS. Data of
      demographics, procedure, and the followed-up were retrieved and analyzed. The
      technical success rate was 95.8%; the clinical success rate was 90.1%. There was
      no catheter-related major stroke or death. The immediate outcomes had no
      statistical difference between groups. During a mean of 27 +/- 20 months (range 2
      88 months) followed-up, 7 (10.3%) restenosis and 12 (17.6%) clinical events were
      identified. The primary patency rate was 95.3, 84.9 and 84.9% at 12, 24 months,
      and final followed-up respectively, which had no statistical difference between
      groups (odds ratio (OR), 2.60; 95% confidence interval (CI), 0.54-12.53; P =
      0.232). The overall clinical event-free survival rate was 93.5, 86.2 and 54.6%,
      respectively, where the result of combined-SAS group was inferior to that of the
      solitary-SAS group (OR, 3.34; 95% CI, 1.02-11.00; P = 0.047). Endovascular
      stenting was safe and feasible for atherosclerotic SAS in patients with OCAS,
      although the combined OCAS may have a significant influence on the long-term
      outcome. Further studies are warrant to investigate the effects of
      revascularization for multiple craniocervical artery stenoses on the cerebral
      hemodynamics and long-term outcomes.

PMID- 22872508
TI  - On the recognition of emotional vocal expressions: motivations for a holistic
      approach.
AB  - Human beings seem to be able to recognize emotions from speech very well and
      information communication technology aims to implement machines and agents that
      can do the same. However, to be able to automatically recognize affective states
      from speech signals, it is necessary to solve two main technological problems.
      The former concerns the identification of effective and efficient processing
      algorithms capable of capturing emotional acoustic features from speech
      sentences. The latter focuses on finding computational models able to classify,
      with an approximation as good as human listeners, a given set of emotional
      states. This paper will survey these topics and provide some insights for a
      holistic approach to the automatic analysis, recognition and synthesis of
      affective states.

PMID- 22872509
TI  - Re-enactment of intended acts from a video presentation by 18- and 24-month-old
      children.
AB  - We used the Re-enactment of intention paradigm to investigate whether children
      would re-enact what an adult intended to do in a video presentation as they do
      when presented with a live demonstration (Meltzoff in Dev Psychol 31(5):838-850,
      1995). Unlike the 18-month-old infants studied by Meltzoff (Dev Psychol 31(5):838
      850, 1995), the 18- and 24-month-olds in the current study did not frequently
      imitate unsuccessful goal-directed actions presented in a video model. Children
      who performed better in the task also tended to share more of their attention
      with the experimenter during co-viewing of the video. Performance on the Re
      enactment of intention task was positively related to categorization score, an
      independent measure of cognitive functioning.

PMID- 22872510
TI  - Risk factors for postoperative pancreatic fistulization subsequent to
      enucleation.
AB  - INTRODUCTION: Pancreatectomies increase the risk of postoperative pancreatic
      fistula (POPF) and pancreatic insufficiency. Pancreatic enucleation preserves
      pancreatic parenchyma, lowers the risk of pancreatic insufficiency, but may
      induce specific complications (tumor recurrence or pancreatic fistulization). The
      aim of this study was to determine the risk factors for POPF following a
      pancreatic enucleation. METHODS: A retrospective analysis was designed based on
      data from patients who underwent pancreatic enucleation in five university
      hospitals (1998-2008). The presence of a pancreatic fistula was determined
      according to the criteria of the International Study Group of Pancreatic Fistula
      (Bassi et al. Surgery 138:8-13, 2005). RESULTS: Fifty-two patients (mean age 52
      years) were included. Histological analysis revealed 35 endocrine tumors (68.6
      %), 6 mucinous and 2 serous cyst adenomas, 2 metastases of renal cancer, and 8
      benign tumors. Nineteen patients (36.5%) suffered postoperative complications
      including 14 POPF (27 %). Median postoperative hospital stay was 12.9 days; 9.1
      days without POPF versus 29 days with POPF (p < 0.05). Size of the tumor, its
      location, histological differentiation, and use of somatostatin analogs were not
      predictors for POPF. We defined the cutoff for POPF at a distance of 2 mm from
      the main pancreatic duct based on 60% risk (<=2 mm) versus 19 % (>2 mm) of POPF
      (p < 0.01). With a mean follow-up of 30.8 months, one patient experienced
      recurrence of the tumor. No patients exhibited a new onset of diabetes or
      pancreatic insufficiency. CONCLUSION: Enucleation for resection of pancreatic
      tumors located at less than or equal to two 2 mm from the main pancreatic duct is
      a risk factor for POPF. Enucleation is a safe and effective treatment for benign
      or borderline pancreatic tumors.

PMID- 22872511
TI  - Evaluation of organic contamination in urban groundwater surrounding a municipal
      landfill, Zhoukou, China.
AB  - This paper investigates the organic pollution status of shallow aquifer sediments
      and groundwater around Zhoukou landfill. Chlorinated aliphatic hydrocarbons,
      monocylic aromatic hydrocarbons, halogenated aromatic hydrocarbons,
      organochlorine pesticides and other pesticides, and polycyclic aromatic
      hydrocarbons (PAHs) have been detected in some water samples. Among the detected
      eleven PAHs, phenanthrene, fluorine, and fluoranthene are the three dominant in
      most of the groundwater samples. Analysis of groundwater samples around the
      landfill revealed concentrations of PAHs ranging from not detected to 2.19 MUg/L.
      The results show that sediments below the waste dump were low in pollution, and
      the shallow aquifer, at a depth of 18-30 m, was heavily contaminated,
      particularly during the wet season. An oval-shaped pollution halo has formed,
      spanning 3 km from west to east and 2 km from south to north, and mainly occurs
      in groundwater depths of 2-4 m. For PAH source identification, both diagnostic
      ratios of selected PAHs and principal component analysis were studied, suggesting
      mixed sources of pyro- and petrogenic derived PAHs in the Zhoukou landfill.
      Groundwater table fluctuations play an important role in the distribution of
      organic pollutants within the shallow aquifer. A conceptual model of leachate
      migration in the Quaternary aquifers surrounding the Zhoukou landfill has been
      developed to describe the contamination processes based on the major contaminant
      (PAHs). The groundwater zone contaminated by leachate has been identified
      surrounding the landfill.

PMID- 22872512
TI  - [Doping in recreational sports activities--pills for better performance].

PMID- 22872513
TI  - The prognostic impact of dynamic ventricular dyssynchrony in patients with
      idiopathic dilated cardiomyopathy and narrow QRS.
AB  - AIMS: Asynchronous myocardial contraction adversely influences left ventricular
      (LV) function and is therefore associated with a poor prognosis in heart failure.
      Exercise-induced change in ventricular dyssynchrony may be an important
      determinant of dynamic changes in cardiac output and mitral regurgitation.
      METHODS AND RESULTS: A prospective, longitudinal study was designed with pre
      defined dyssynchrony index and outcome variables to test the hypothesis that
      dynamic dyssynchrony is associated with worse long-term event-free survival in
      patients with dilated cardiomyopathy (DCM) and 'narrow' QRS complex. One-hundred
      eighty patients (62 +/- 8 years; 110 males) with NYHA class II-III, idiopathic
      DCM, ejection fraction <=35%, and QRS duration <120 ms were selected. All the
      patients underwent standard Doppler echo, colour tissue velocity imaging (DTI),
      and supine bicycle exercise stress echocardiography. Cardiac synchronicity was
      defined, at rest and at peak exercise, as DTI velocity opposing-wall delay
      (significant if >=65 ms). Outcome was defined as freedom from death, heart
      transplantation, or LV-assist device implantation, over a median follow-up of 48
      months, and a Cox proportional hazards model was used for survival analysis. At
      baseline examination, DCM patients showed a reduced LV ejection fraction (31 +
      4%). A significant electromechanical delay in 58 patients (32%). At the peak of
      physical exercise, a significant electromechanical delay was detected in 103
      patients (57%). There were 41 events during the follow-up (23%): 28 cardiac
      deaths, 8 heart transplantations, and 5 LV-assist device implantations over 4
      years. When adjusted for confounding baseline variables, LV end-diastolic volume,
      restrictive mitral flow pattern, severity of mitral regurgitation, and the
      presence of exercise-induced intraventricular dyssynchrony were the only
      independent determinants of an adverse outcome. CONCLUSION: In patients with
      idiopathic DCM and narrow QRS, the increase in echocardiographic dyssynchrony
      during exercise was the strongest predictor of less favourable event-free
      survival.

PMID- 22872514
TI  - Redefining normal reference ranges for echocardiography: a major new individual
      person data meta-analysis.
AB  - Current recommended reference ranges for echocardiographic measurements may not
      be relevant to the diverse world population they are applied to. A new study, the
      echocardiographic normal reference ranges of the left heart (EchoNoRMAL) study,
      is an individual person data meta-analysis of standard echocardiographic
      measurements which aims to re-define normal reference ranges of left heart
      dimensions, areas, volumes, mitral inflow and tissue Doppler, and associated
      calculated variables.

PMID- 22872515
TI  - Introductory paragraph - Volume 26, Issue 9.

PMID- 22872517
TI  - Predicting the factors of lateral lymph node metastasis in papillary
      microcarcinoma of the thyroid in eastern China.
AB  - INTRODUCTION: Lateral lymph node metastasis is common in papillary thyroid
      microcarcinoma (PTMC). The present study evaluated the clinicopathologic
      characteristics and ultrasonographic (US) findings in predicting lateral LNM from
      PTMC in eastern China. MATERIALS AND METHODS: A total of 176 patients with
      confirmed PTMC by final histological examination who underwent central lymph node
      dissection (LND) and lateral LND were enrolled in our study. The
      clinicopathological and US data from the cases were analyzed retrospectively to
      determine the independent predictive factors for lateral LNM. Then, a scoring
      system was developed on the basis of independent factors. The sum of the points
      for individuals was evaluated for the value in predicting lateral LNM. RESULTS:
      Central LNM, underlying Hashimoto's thyroiditis, upper pole location, no well
      defined margin and presence of calcifications were independent predictive factors
      for lateral LNM on multivariate analysis. Clinicopathological and US index points
      were statistically significant, with <= 2 favoring lateral LNM negativity with a
      sensitivity of 83.3 %, positive predictive value of 89.6 % and negative
      predictive value of 72.9 %. CONCLUSIONS: When the evaluation for lateral lymph
      nodes from a preoperative approach is inadequate or not obvious, our scoring
      system for prediction of lateral LNM can be another choice. Patients with
      clinicopathological and US index points <= 2 could be considered as lateral LNM
      negative, so more diagnostic approach is recommended for patients with
      clinicopathological and US index points >2.

PMID- 22872518
TI  - Retrospective study assessing the role of MRI in the diagnostic procedures for
      early breast carcinoma: a correlation of new foci in the MRI with tumor
      pathological features.
AB  - BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast
      cancer has generated significant debate. We analyze the role of breast MRI in the
      detection of additional disease and the need to perform additional biopsies in
      early breast carcinoma patients. In addition, we correlate the detection of new
      foci with tumor pathological features. METHODS: Early breast carcinoma patients
      that had undergone an MRI as well as a mammography as diagnostic procedures were
      included in the study. The following pathologic features were studied: carcinoma
      type, histological grade, estrogen receptors (ER), progesterone receptors (PR),
      HER2 and Ki67. Univariate analysis was conducted to ascertain significant
      correlation among detection of new foci and each of the tumor pathological
      features. RESULTS: Data from 98 patients have been analyzed: median age 49 years
      (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %),
      (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n =
      6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 >= 25 % (n
      = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8,
      8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an
      additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We
      found a statistically significant correlation between new foci in MRI and high
      Ki67 >= 25 % (p < 0.005). No other statistically significant correlation was
      established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring
      an additional biopsy 20 %. Tumors with high proliferative index were
      significantly correlated with the detection of new foci in MRI.

PMID- 22872519
TI  - VEGF-A and VEGF-B mRNA expression in gastro-oesophageal cancers.
AB  - INTRODUCTION: Angiogenesis is essential for the local growth, invasion and
      metastasis of the tumours. Vascular endothelial growth factors (VEGFs) play a
      crucial role in tumour angiogenesis. The aim of our study was to quantify the
      expression of several VEGF family molecules in human gastro-oesophageal cancers
      and to analyse possible correlations between genes expression and clinico
      pathological features. MATERIALS AND METHODS: Gene expression was quantified in
      43 gastro-oesophageal paired samples using qRT-PCR with TaqMan probes specific to
      VEGF-A, including soluble transcript variants and VEGF-B genes. RESULTS: VEGF-A,
      including the studied splice variants and VEGF-B mRNAs were expressed in both
      tumour and peritumour mucosa. The expression of VEGF-A and its isoforms was
      higher in tumour compared with paired peritumour mucosa, while no significant
      difference was observed in VEGF-B expression. VEGF-A expression tended to
      correlate with tumour invasion. CONCLUSION: VEGF-A has a tendency to over-express
      in gastro-oesophageal cancers, while VEGF-B does not seem involved in these
      tumours. Further studies are required to establish the utility of anti-VEGF-A
      therapy and to find biomarkers for pathogenesis or response to therapy in gastro
      oesophageal tumours.

PMID- 22872521
TI  - Intraoperative ultrasound guidance for excision of non-palpable invasive breast
      cancer: a hospital-based series and an overview of the literature.
AB  - Intraoperative ultrasound (IOUS) can be used in the operation theatre for
      localization of non-palpable breast cancers. In this prospective cohort study, we
      compared the yield of IOUS to guidewire localization (GWL). A total of 258
      consecutive patients with non-palpable invasive breast cancer underwent breast
      conserving surgery between 1999 and 2010. GWL was performed in 138 (54 %) and
      IOUS in 120 (46 %) patients. Tumor dimensions, resection volume, margin status
      and re-excision rates were compared by means of multivariate regression analysis.
      The groups were similar in terms of age, histological subtype and presence of
      DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm, P < 0.001), while
      microcalcifications were more common in the GWL group (19 vs. 3 %, P < 0.001).
      Even after stratification for tumor diameter, presence of DCIS and findings on
      mammography, resection volumes were similar in both groups. Tumor-free resection
      margins were obtained in >93 % of patients (93.5 % with GWL vs. 93.3 % with IOUS,
      P = 0.958) and re-excision was performed in 11 % of patients undergoing GWL and
      12.5 % of patients undergoing IOUS (P = 0.684). For localization of non-palpable
      breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar
      results in terms of complete tumor removal, re-excision rate and excised volume.

PMID- 22872520
TI  - The influence of gender and group membership on food safety: the case of meat
      sellers in Bodija market, Ibadan, Nigeria.
AB  - We describe a study to assess the bacteriological quality and safety of meat in
      Bodija market in Ibadan and to investigate the influence of gender and group
      membership on food safety. Mixed methods were used to gather information on meat
      safety and related socioeconomic factors. These methods included a participatory
      urban appraisal, focus group discussions with eight butchers' associations, in
      depth discussions with six key informants, a questionnaire study of 269 meat
      sellers and a cross-sectional survey of meat quality (200 samples from ten
      associations). We found that slaughter, processing and sale of beef meat take
      place under unhygienic conditions. The activities involve both men and women,
      with some task differentiation by gender. Meat sold by association members is of
      unacceptable quality. However, some groups have consistently better quality meat
      and this is positively correlated with the proportion of women members. Women
      also have significantly better food safety practice than men, though there was no
      significant difference in their knowledge of and attitude towards food safety.
      Most meat sellers (85 %) reported being ill in the last 2 weeks and 47 % reported
      experiencing gastrointestinal illness. Eating beef, eating chicken, eating offal,
      consuming one's own products and belonging to a group with poor quality of meat
      were all strong and significant predictors of self-reported gastrointestinal
      illness. We include that gender and group membership influence meat quality and
      self-reported gastrointestinal illness and that butchers' associations are
      promising entry points for interventions to improve food safety.

PMID- 22872522
TI  - Locoregional lymph node involvement on 18F-FDG PET/CT in breast cancer patients
      scheduled for neoadjuvant chemotherapy.
AB  - The optimal method for locoregional staging in patients treated with neoadjuvant
      chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy
      sentinel lymph node biopsy (SLNB), remains subject of debate. The aim of this
      study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph
      node metastases in primary breast cancer patients scheduled for NAC. 311 breast
      cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone
      position with hanging breasts. A panel of four experienced reviewers examined
      PET/CT images, blinded for other diagnostic procedures. FDG uptake in
      locoregional nodes was determined qualitatively using a 4-point scale (0 =
      negative, 1 = questionable, 2 = moderately intense, and 3 = very intense).
      Results were compared with pathology obtained by US-guided fine needle aspiration
      or SLNB prior to NAC. All FDG-avid extra-axillary nodes were considered
      metastatic, based on the previously reported high positive predictive value of
      the technique. Sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of FDG-avid nodes for the detection of axillary
      metastases (score 2 or 3) were 82, 92, 98, 53, and 84 %, respectively. Of 28
      patients with questionable axillary FDG uptake (score 1), 23 (82 %) were node
      positive. Occult lymph node metastases in the internal mammary chain and
      periclavicular area were detected in 26 (8 %) and 32 (10 %) patients,
      respectively, resulting in changed regional radiotherapy planning in 50 (16 %)
      patients. In breast cancer patients scheduled for NAC, PET/CT renders pre
      chemotherapy SLNB unnecessary in case of an FDG-avid axillary node, enables
      axillary response monitoring during or after NAC, and leads to changes in
      radiotherapy for a substantial number of patients because of detection of occult
      N3-disease. Based on these results, we recommend a PET/CT as a standard staging
      procedure in breast cancer patients scheduled for NAC.

PMID- 22872524
TI  - Primary culture of mantle cells of bivalve mollusc, Paphia malabarica.

PMID- 22872523
TI  - Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients
      with metastatic breast cancer.
AB  - The purpose of this study was to investigate the safety, tolerability, and
      pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in
      patients with metastatic breast cancer. In this open-label, dose-finding, phase
      1b study, patients received motesanib 50 or 125-mg orally once daily (QD),
      beginning day 3 of cycle 1 of chemotherapy, continuously in combination with
      either paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 28-day cycle (Arm A) or
      docetaxel 100 mg/m(2) on day 1 every 21-day cycle (Arm B). Dose escalation to
      motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs,
      primary endpoint) was <= 33 %. If the maximum tolerated dose (MTD) of motesanib
      was established in Arm B, additional patients could receive motesanib at the MTD
      plus docetaxel 75 mg/m(2). Forty-six patients were enrolled and 45 received >= 1
      dose of motesanib. The incidence of DLTs was <33 % in all cohorts; thus,
      motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3
      motesanib-related adverse events including cholecystitis (2 patients) and
      hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar
      to those reported in previous studies. The objective response rate was 56 % among
      patients with measurable disease at baseline who received motesanib in
      combination with taxane-based chemotherapy. The addition of motesanib to either
      paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of
      motesanib. The objective response rate of 56 % suggests a potential benefit of
      motesanib in combination with taxane-based chemotherapy.

PMID- 22872525
TI  - Effect of postmortem time interval on in vitro culture potential of goat skin
      tissues stored at room temperature.
AB  - Animal cloning using somatic cell nuclear transfer technology has renewed the
      interest in postmortem tissue storage, since these tissues can be used to
      reintroduce the lost genes back into the breeding pool in animal agriculture,
      preserve the genetic diversity, and revive the endangered species. However, for
      successful cloning of animals, integrity of nuclear DNA is essential. Cell
      viability and their potential to in vitro culture ensure nuclear integrity. The
      aim of this study was to determine the limits of postmortem time interval within
      which live cells can be recovered from goat skin tissues. To test the postmortem
      tissue storage limits, we cultured 2-3 mm(2) skin pieces (n = 70) from the ears
      of three breeds of goats (n = 7) after 0, 2, 4, and 6 days of postmortem storage
      at 24 degrees C. After 10 days of culture, outgrowth of fibroblast-like cells
      (>50 cells) around the explants was scored. All the explants irrespective of
      breed displayed outgrowth of cells on the dish containing fresh tissues (i.e.,
      day 0 of storage). However, the number of explants exhibiting outgrowth reduced
      with increasing time interval. Only 53.85 % explants displayed outgrowth after 2
      days of tissue storage. The number of explants displaying outgrowth was much
      smaller after 4 (16.67 %) and 6 days (13.3 %) of storage. In general, the number
      of outgrowing cells per explant, on a given day, also decreased with increasing
      postmortem storage time interval. To test the differences between cell cultures,
      we established secondary cultures from one of the goats exhibiting outgrowth of
      cells after 6 days of tissue storage and compared them to similar cells from
      fresh tissues. Comparison of both the cell lines revealed similar cell morphology
      and growth curves and had doubling times of 23.04 and 22.56 h, respectively.
      These results suggest that live cells can be recovered from goat (and perhaps
      other animal) tissues stored at room temperature even after 6 days of their death
      with comparable growth profiles and, thus, can be used for tissue banking for
      preservation of superior genetics, genetic diversity, and cloning of animals.

PMID- 22872526
TI  - Predicting compensation voltage for singly-charged ions in high-field asymmetric
      waveform ion mobility spectrometry (FAIMS).
AB  - Correlation between compensation voltage (CV) and the m/z ratio of singly-charged
      ions was elucidated. The experimental data for various alkylammonium homologues
      and various pharmaceutical compounds were used to construct empirical calibration
      curves that were fit using commercial regression analysis software packages. The
      best fit equations were applied to calculate the CV differences (DeltaCV) in pure
      N(2) and N(2)/He 50/50 carrier gasses and CV values for a variety of compounds
      using only m/z values. The calculated values were in good agreement with
      experimental data and DeltaCV values exhibited a very strong correlation with
      m/z. Application of these empirical calculations may provide a powerful CV
      prediction tool for researchers using high-field asymmetric waveform ion mobility
      spectrometry (FAIMS) and increase the value of FAIMS as an analytical method.

PMID- 22872528
TI  - [What are the chances for young medical doctors to acquire scientific
      qualification in internal medicine?].

PMID- 22872527
TI  - A history of physician suicide in America.
AB  - Over the course of the last century, physicians have written a number of articles
      about suicide among their own. These articles reveal how physicians have
      fundamentally conceived of themselves, how they have addressed vulnerability
      among their own, and how their self-identification has changed over time, due, in
      part, to larger historical changes in the profession, psychiatry, and
      suicidology. The suicidal physician of the Golden Age (1900-1970), an expendable
      deviant, represents the antithesis of that era's image of strength and
      invincibility. In contrast, the suicidal physician of the modern era (1970
      onwards), a vulnerable human being deserving of support, reflects that era's
      frustration with bearing these unattainable ideals and its growing emphasis on
      physician health and well-being. Despite this key transition, specifically the
      acknowledgment of physicians' limitations, more recent articles about physician
      suicide indicate that Golden Age values have endured. These persistent emphases
      on perfection and discomfort with vulnerability have hindered a comprehensive
      consideration of physician suicide, despite one hundred years of dialogue in the
      medical literature.

PMID- 22872529
TI  - [Interventional treatment of varicose veins: recent advances].

PMID- 22872530
TI  - [Bariatric surgery: current knowledge].

PMID- 22872531
TI  - [Physical exercise in patients with dementia].

PMID- 22872532
TI  - [Soft-tissue sarcoma: recent developments].

PMID- 22872533
TI  - [Syphilis und gonorrhoea--sexually transmitted infections of the past?].

PMID- 22872534
TI  - [Sepsis. Update 2012].

PMID- 22872535
TI  - [Cardiovascular diseases in pregnancy: facts of the new guideline].

PMID- 22872536
TI  - [Primary arterial hypertension: update 2012].

PMID- 22872537
TI  - [Pulmonary rehabilitation].

PMID- 22872538
TI  - [Career development of young scientists in internal medicine. Position paper of
      the German Society of Internal Medicine ].

PMID- 22872539
TI  - [25-year-old traveller returning home with a furuncular lesion].

PMID- 22872540
TI  - [Abdominal free air without signs of perforated abdominal viscus  during non
      invasive ventilation].
AB  - HISTORY: A 19-year-old patient suffering from Duchenne muscular dystrophy was
      admitted to our hospital with an acute bronchopulmonary infection. Four months
      ago noninvasive ventilation was started because of hypercapnic respiratory
      failure. Mechanical ventilation had been used so far only at night. At the time
      of admission spontaneous breathing was not possible due to exhaustion of the
      respiratory muscles. The patient suffered from fever, limited cough strength and
      dyspnoea at rest. The abdomen was distended because of intestinal gas without
      clinical signs of acute abdomen. INVESTIGATIONS: Blood gas analysis showed
      respiratory acidosis even under mechanical ventilation. Laboratory tests showed
      an elevation of the inflammation indicating parameters. X-rays of the chest
      showed elevated diaphragms. Within the next days pneumonia could be seen in the
      left lower lobe. The patient had to be under mechanical ventilation almost 24
      hours per day. Hypercapnia and respiratory acidosis normalized and the patient
      was able to breathe spontaneously for longer periods. The following days
      cutaneous emphysema developed and X-rays revealed free abdominal air on day 9 of
      the hospital stay. DIAGNOSIS, TREATMENT AND COURSE: The radiological findings
      have been confirmed during follow up X-rays without any clinical correlate.
      Inflammatory markers were decreasing. After the pneumonia had healed almost
      completely, the times on mechanical ventilation could be reduced. Subphrenic air
      resolved completely without any intervention. CONCLUSION: Free subphrenic air
      without any clinical signs of acute abdomen does not necessarily force a surgical
      exploration. Under frequent follow up investigations a wait-and-see strategy
      could be justified. An explanation for the subphrenic air could be an
      interstitial emphysema due to increased intrathoracic pressure caused by the
      prolonged noninvasive ventilation, releasing the air through the diaphragmatic
      gaps into the abdomen.

PMID- 22872541
TI  - [Impact of demographic chance on pharmaceutical expenses in private health
      insurance--a scenario-based analysis].
AB  - Health Insurance costs in Germany have grown constantly over the last years. This
      increase of costs is not only observable in the total consideration but also in
      all single items. An outstanding growth rate exists in the field of
      pharmaceutical expenses. Detailed analyses of distribution and development of
      these costs, separated by age and indication groups, are currently only
      sporadically available and mostly focusing on the Statutory Health Insurance
      system in Germany. This research article is based on an initial data analysis and
      focuses on the question how pharmaceutical expenses in a German private health
      insurance company will develop until the year 2050, if the observed trend of the
      past years continues in the same way. This analysis focuses on different age
      groups. The objective is the demonstration of several scenarios, which illustrate
      the level of influence of different parameters (demographic changes, developments
      of prices for pharmaceuticals). Based on the cognition of certain effects
      measures for handling the growing challenge of financing the health system can be
      deduced. As a result, both demographic changes and price effects have an
      significant impact on the future development of per capita pharmaceutical
      expenses. Whereas older age groups will still cause the highest costs, the middle
      aged people will show the highest growth rates. This strong cost increase is not
      sustainable for the German health insurance system. In addition to previous
      measures of a regulatory health policy (especially improved cost-benefit
      assessments) the article shows new approaches for an intensified prevention and
      health promotion.

PMID- 22872542
TI  - The influence of overweight and obesity on maternal soluble fms-like tyrosine
      kinase 1 and its relationship with leptin during pregnancy.
AB  - We studied obesity-related differences in the relation of maternal levels of
      leptin to levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic
      protein that influences placentation and risk of adverse pregnancy outcomes. In a
      prospective cohort of 286 gravidas, we measured maternal serum levels of sFlt1
      and leptin at 5 time points across pregnancy. Analyses stratified on prepregnancy
      body mass index (<25 vs >=25) were done using mixed linear models. The mean
      leptin concentrations were significantly higher in overweight/obese compared to
      normal-weight women, while mean sFlt1 levels in second and third trimester were
      significantly higher in normal weight compared to overweight/obese women. The
      relationship between sFlt1 and leptin differed between the 2 strata. After
      controlling for maternal weight, a 1 ng/mL increase in leptin was associated with
      an 19.4 pg/mL increase in sFlt1 (P = .01) in normal-weight women, while leptin
      was not associated with sFlt1 (beta = 1.1, P = .75) in overweight/obese women.
      Such differences suggest that metabolic differences in overweight/obese women
      compared to their normal weight peers may differentially impact the physiologic
      changes during pregnancy.

PMID- 22872543
TI  - Fetal swallowing as a protective mechanism against oligohydramnios and
      polyhydramnios in late gestation sheep.
AB  - Our objectives were to (1) quantify the relationship between daily swallowed
      volume and amniotic fluid volume (AF volume) in late gestation ovine fetuses and
      (2) use the resulting regression equation to explore the role of swallowing in
      regulating AF volume. Daily swallowed volume ranged from 36 to 1963 mL/d while
      experimental AF volume ranged from 160 to 6150 mL (n = 115). Swallowed volume was
      near zero when AF volume was far below normal, a maximum of 635 +/- 41 (standard
      error) mL/d when AF volume was 1682 +/- 31 mL and did not increase further with
      higher AF volumes. Computer simulations predicted that fetal swallowing would (1)
      return AF volume to normal in 5 to 6 days following an acute volume change in the
      absence of changes in other amniotic inflows or outflows and (2) stabilize AF
      volume in 4 to 8 days following sustained alterations in amniotic inflows or
      outflows other than swallowing. CONCLUSIONS: The volume of AF swallowed each day
      by the fetus is a strong function of AF volume and reaches a maximum when mild
      polyhydramnios develops. With deviations in AF volume from normal, changes in
      fetal swallowing protect against oligohydramnios and polyhydramnios because the
      changes in swallowing over time reduce the extent of the AF volume change.
      However, with experimental changes in AF volume stabilizing in 1 to 2 days, it
      appears that swallowing is not the major regulator of AF volume.

PMID- 22872544
TI  - Subcellular redistribution of NHERF1 in response to dehydroepiandrosterone (DHEA)
      administration in endometrial glands of Wistar rats.
AB  - To understand the regulation of Na(+)/H(+) exchanger regulatory factor (NHERF1)
      in polycystic ovarian syndrome, we studied the expression of NHERF1 in uterus of
      Wistar rats injected with (6 mg/kg) of dehydroepiandrosterone (DHEA) for 7 and 20
      days. Immunohistochemistry analysis of NHERF1 showed a substantial shift in the
      intracellular localization of NHERF1 in endometrial glands and areas of luminal
      epithelium as early as 7 days of DHEA administration. The NHERF1 accumulated in
      the "Golgi apparatus area" virtually in all the glands in the 7-day protocol, and
      in the majority of the glands of 20-day protocol. In contrast, NHERF1 is
      expressed in the apical membrane and slightly in the cytoplasm of the control
      epithelium. The subcellular redistribution of NHERF1 could affect the sorting of
      proteins to the apical membrane and the organization of the apical compartment.

PMID- 22872545
TI  - Increased serum concentrations of circulating glycocalyx components in HELLP
      syndrome compared to healthy pregnancy: an observational study.
AB  - Severe inflammation has been shown to induce a shedding of the endothelial
      glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor alpha
      (TNF-alpha), impede the thickness of the EGX. While a controlled inflammatory
      reaction occurs already in normal pregnancy, women with hemolysis, elevated liver
      enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory
      response. This study investigates the shedding of the glycocalyx during normal
      pregnancy and in women with HELLP syndrome. Glycocalyx components (syndecan 1,
      heparan sulfate, and hyaluronic acid) were measured in serum of healthy women
      throughout pregnancy (4 time points, n = 26), in women with HELLP syndrome (n =
      17) before delivery and in nonpregnant volunteers (n = 10). Serum concentrations
      of TNF-alpha and soluble TNF-alpha receptors (sTNF-Rs) were assessed once in all
      3 groups. Syndecan 1 serum concentrations constantly rose throughout normal
      pregnancy. Immediately before delivery, a 159-fold increase was measured compared
      to nonpregnant controls (P < .01). Even higher amounts were observed in patients
      with HELLP prior to delivery (median 12 252 ng/mL) compared to healthy women
      matched by gestational age (median 5943 ng/mL; P < .01). Relevantly, increased
      serum levels of heparan sulfate, hyaluronic acid, and sTNF-Rs were only detected
      in patients with HELLP (P < .01). These findings suggest that considerable
      amounts of syndecan 1 are released into maternal blood during uncomplicated
      pregnancy. The HELLP syndrome is associated with an even more pronounced shedding
      of glycocalyx components. The maternal vasculature as well as the placenta has to
      be discussed as a possible origin of circulating glycocalyx components.

PMID- 22872546
TI  - Meta-analysis of effect sizes reported at multiple time points: a multivariate
      approach.
AB  - BACKGROUND: Many comparative studies report results at multiple time points. Such
      data are correlated because they pertain to the same patients, but are typically
      meta-analyzed as separate quantitative syntheses at each time point, ignoring the
      correlations between time points. PURPOSE: To develop a meta-analytic approach
      that estimates treatment effects at successive time points and takes account of
      the stochastic dependencies of those effects. METHODS: We present both fixed and
      random effects methods for multivariate meta-analysis of effect sizes reported at
      multiple time points. We provide formulas for calculating the covariance (and
      correlations) of the effect sizes at successive time points for four common
      metrics (log odds ratio, log risk ratio, risk difference, and arcsine difference)
      based on data reported in the primary studies. We work through an example of a
      meta-analysis of 17 randomized trials of radiotherapy and chemotherapy versus
      radiotherapy alone for the postoperative treatment of patients with malignant
      gliomas, where in each trial survival is assessed at 6, 12, 18, and 24 months
      post randomization. We also provide software code for the main analyses described
      in the article. RESULTS: We discuss the estimation of fixed and random effects
      models and explore five options for the structure of the covariance matrix of the
      random effects. In the example, we compare separate (univariate) meta-analyses at
      each of the four time points with joint analyses across all four time points
      using the proposed methods. Although results of univariate and multivariate
      analyses are generally similar in the example, there are small differences in the
      magnitude of the effect sizes and the corresponding standard errors. We also
      discuss conditional multivariate analyses where one compares treatment effects at
      later time points given observed data at earlier time points. LIMITATIONS:
      Simulation and empirical studies are needed to clarify the gains of multivariate
      analyses compared with separate meta-analyses under a variety of conditions.
      CONCLUSIONS: Data reported at multiple time points are multivariate in nature and
      are efficiently analyzed using multivariate methods. The latter are an attractive
      alternative or complement to performing separate meta-analyses.

PMID- 22872547
TI  - Dietary calcium intake, vitamin D levels, and breast cancer risk: a dose-response
      analysis of observational studies.
AB  - Results from the recent meta-analysis suggested a favorable effect of dietary
      calcium and vitamin D levels on breast cancer risk. However, the relationship of
      dietary calcium and vitamin D levels with breast cancer risk is unclear. Thus,
      the dose-response relationship was assessed by restricted cubic spline model and
      multivariate random-effect meta-regression. Results suggested that women might
      suffer from the lowest risk of breast cancer with dietary calcium intake of about
      600 mg/day, dietary vitamin D intake of about 400 IU/day, and serum vitamin D
      levels of about 30 ng/ml.

PMID- 22872548
TI  - Fire drill: inattentional blindness and amnesia for the location of fire
      extinguishers.
AB  - Fire extinguishers can save lives and are placed in locations that make them
      easily accessible and in plain view in case of an emergency. However, despite
      having viewed these bright red objects many times, people may be unaware of their
      precise locations or even of the fact that they have seen them so often in their
      workplace environment. We tested the ability of occupants of an office building
      to recall the location of the nearest fire extinguisher, as well as other objects
      (e.g., clock, drinking fountain). Despite years of exposure to it, a majority
      failed to remember the location of the nearest fire extinguisher, although they
      were able to locate it relatively quickly when asked to search for it. The
      results support an important distinction between seeing and noticing objects and
      reveal a novel form of inattentional amnesia for salient objects. The study also
      created an important learning event via failed retrieval, which could be
      essential to survival.

PMID- 22872549
TI  - Working memory load can both improve and impair selective attention: evidence
      from the Navon paradigm.
AB  - Selective attention to relevant targets has been shown to depend on the
      availability of working memory (WM). Under conditions of high WM load, processing
      of irrelevant distractors is enhanced. Here we showed that this detrimental
      effect of WM load on selective attention efficiency is reversed when the task
      requires global- rather than local-level processing. Participants were asked to
      attend to either the local or the global level of a hierarchical Navon stimulus
      while keeping either a low or a high load in WM. In line with previous findings,
      during attention to the local level, distractors at the global level produced
      more interference under high than under low WM load. By contrast, loading WM had
      the opposite effect of improving selective attention during attention to the
      global level. The findings demonstrate that the impact of WM load on selective
      attention is not invariant, but rather is dependent on the level of the to-be
      attended information.

PMID- 22872550
TI  - Stress fracture of the fourth metatarsal in a relapsed clubfoot of a 5.5-year-old
      child.
AB  - Stress fractures are uncommon in skeletally immature patients and usually affect
      adolescents involved in competitive sports, whereas they are very rare in young
      children. Involvement of the fourth metatarsal is very infrequent and has been
      associated with metatarsus adductus deformities. The authors describe a stress
      fracture of the proximal fourth metatarsal occurred in a 5.5-year-old child with
      a relapsed clubfoot. Operative correction of the deformity and cast
      immobilization provided consolidation of the fracture. Stress fractures of
      lateral metatarsals may represent a possible source of pain in recurrent
      clubfeet, even in young children. In these cases, early correction of the
      deformity is required. 

PMID- 22872551
TI  - Revision rhinoplasty.

PMID- 22872552
TI  - Ethical considerations in revision rhinoplasty.
AB  - The problems that arise when reviewing another surgeon's work, the financial
      aspects of revision surgery, and the controversies that present in marketing and
      advertising will be explored. The technological advances of computer imaging and
      the Internet have introduced new problems that require our additional
      consideration.

PMID- 22872553
TI  - Psychological considerations in the revision rhinoplasty patient.
AB  - The nose contributes greatly to the facial aesthetic. Derangements in nasal
      cosmesis, whether from surgery, trauma, or natural causes, have a plethora of
      implications for the emotional well-being of the individual. Rhinoplasty and
      revision rhinoplasty are both facial cosmetic operations that have potentially
      profound cosmetic, and therefore psychological, implications for the patient.
      Although many revision rhinoplasty patients have hopeful yet realistic surgical
      expectations, there is a subset of revision rhinoplasty patients having
      underlying psychological disturbances that may negatively affect the surgical
      outcome, no matter how favorable the surgical improvement. In this article, the
      various psychological disorders impacting revision rhinoplasty patients will be
      discussed. In addition, this article will familiarize the revision rhinoplasty
      surgeon with many of the hallmark characteristics of psychopathology, as well as
      the typical emotional presentation of the well-adjusted revision rhinoplasty
      patient, to facilitate differentiation between these seemingly similar, but
      distinctly different patient groups.

PMID- 22872554
TI  - Common technical causes of the failed rhinoplasty.
AB  - The adverse rhinoplasty outcome may result from a wide variety of dissimilar
      causes. Although these causes include psychiatric patient disturbances and
      severely aberrant wound-healing responses, by far the most common etiology of the
      failed rhinoplasty is technical failure on behalf of the surgeon. Moreover, a
      disproportionate number of technical shortcomings stem from errors in basic
      rhinoplasty technique. Hence, mastery of rhinoplasty fundamentals will prevent a
      large number of novice errors that often taint the cosmetic outcome. Because many
      of the remaining technical errors stem from overaggressive tissue removal, tissue
      sparing rhinoplasty techniques will also prevent many common causes of technical
      failure. This article identifies some of the more common technical errors
      associated with the unsuccessful cosmetic rhinoplasty and also provides insights
      as to their avoidance.

PMID- 22872555
TI  - An anatomic basis for revision rhinoplasty.
AB  - As the popularity of rhinoplasty has increased, so have the expectations of both
      patients and surgeons alike. Revision rhinoplasty has become an evolving field
      with unique challenges. One must first address the patient's specific concerns
      and emotional issues. To properly repair the inadequacies of a failed
      rhinoplasty, the surgeon must thoroughly analyze and understand the anatomic
      causes leading to why the patient needs revision surgery.

PMID- 22872556
TI  - Revision of the functionally devastated nasal airway.
AB  - Functional rhinoplasty can be especially challenging in a patient who has had
      previous surgery, trauma, anatomic abnormalities, or systemic disease affecting
      the nasal mucosa. A thorough analysis of the type and location of the obstruction
      is critical, and only after identifying the precise anatomic cause of the problem
      can surgical planning begin. Scarring, altered anatomy, and disrupted tissue
      planes all complicate this process. Structural support and nasal mucosa often
      require augmentation with autogenous grafts from the ear, rib, or other portions
      of the nasal cavity. Attention to nasal support mechanisms, the internal and
      external nasal valves, and internal lining during primary surgery may help to
      avoid future complications. Through careful analysis and planning, proper
      function may be restored to a functionally devastated nasal airway.

PMID- 22872557
TI  - Revision of the surgically overshortened nose.
AB  - The short nose deformity may arise from multiple etiologies including iatrogenic
      following rhinoplasty. The weakening of the cartilaginous support and the
      contractile forces imposed by the healing soft tissue envelope may result in the
      short nose deformity. The focus of this article is to present the senior author's
      approach to this nasal deformity.

PMID- 22872558
TI  - Secondary rhinoplasty: management of the overresected dorsum.
AB  - Any discussion of grafting the dorsum in secondary rhinoplasty must take into
      account the different indications (aesthetic, augmentation, and structure) as
      well as recent changes in materials and techniques (fascia, diced cartilage). We
      have placed solid dorsal grafts with diced cartilage grafts either as an isolated
      diced cartilage graft in fascia graft or as the aesthetic dorsal contour layer of
      a composite reconstruction. The rational for this profound change in selection
      and indication of dorsal grafts for revising the overresected dorsum will become
      clear as the various alternative materials and techniques are analyzed.
      Currently, we only employ autogenous tissues.

PMID- 22872559
TI  - Revision of the overresected nasal tip complex.
AB  - Tip deformities resulting from previous nasal surgery range from mild to
      profound. For the mild deformity, morbidity is low and successful correction is
      usually achieved with a modest and targeted surgical adjustment. However, for the
      profound deformity, overt cosmetic deformities and corresponding functional
      impairment are the byproducts of severe derangements in skeletal architecture.
      Hence, for the severely damaged nasal tip, a complex surgical revision in which
      the decimated nasal tip framework is reconstructed with autologous cartilage
      grafts is essential. However, rebuilding the decimated nasal tip is a challenging
      and risky procedure that is best left to the seasoned rhinoplasty specialist.
      Careful assessment of the previously operated tissues, combined with an accurate
      cosmetic analysis, must be juxtaposed with the patient's cosmetic desires to
      derive an individualized and effective treatment plan. Atraumatic soft tissue
      technique, combined with a strategic yet balanced and judicious application of
      graft material, often culminate in satisfactory surgical outcomes. Proper
      assessment, technical skill, and sound clinical judgment are all critical
      ingredients in successful restoration of the surgically compromise nasal tip.

PMID- 22872560
TI  - Deprojection of the nasal tip in revision rhinoplasty.
AB  - Overprojection in revision rhinoplasty can be the result of underaddressed
      anatomic variations, iatrogenic causes including overresection of the nasal
      dorsum, or the healing process. Management of nasal tip overprojection in
      revision rhinoplasty can be very difficult, and the revision rhinoplasty surgeon
      must have a multitude of techniques available to treat the various causes of
      nasal tip overprojection. An algorithm is presented to properly approach and
      treat nasal tip overprojection.

PMID- 22872561
TI  - Revision of the cleft lip nose.
AB  - Secondary or revision rhinoplasty for the cleft nasal deformity represents one of
      the most challenging problems in rhinoplasty surgery. The secondary nasal
      deformity of the unilateral cleft lip involves a retrodisplaced dome of the
      ipsilateral nasal tip, hooding of the alar rim, a secondary alar-columellar web,
      and other deficiencies. This article discusses techniques to achieve the best
      possible outcome for patients with cleft nasal deformities. We emphasize the
      importance of early intervention by way of primary cleft rhinoplasty and
      highlight the typical challenges presented in delayed (secondary) or revision
      cleft rhinoplasty. We describe how the sliding flap cheilorhinoplasty effectively
      corrects these deformities using a laterally based chondrocutaneous flap via an
      open rhinoplasty approach. Columellar struts and shield grafts are some of the
      techniques combined with this approach to produce optimal results.

PMID- 22872562
TI  - Revision of severe nasal trauma.
AB  - Facial trauma commonly includes injury to the nose and perinasal area. In this
      review, we will focus on the sequelae of severe nasal trauma and provide examples
      of correction of the severely deviated nose, the severely collapsed nose, and
      revision of a traumatic deformity after prior rhinoplasty. We will then discuss
      coexistent deformities of perinasal regions in addition to functional and
      posttraumatic nasal correction, including posttraumatic periorbital deformities.

PMID- 22872563
TI  - Makeup pencils in plastic surgery.

PMID- 22872567
TI  - Sequence and phylogenetic analysis of host-range (E3L, K3L, and C7L) and
      structural protein (B5R) genes of buffalopox virus isolates from buffalo, cattle,
      and human in India.
AB  - Buffalopox virus (BPXV), a close variant of vaccinia virus (VACV) has emerged as
      a zoonotic pathogen. The host tropism of poxviruses is governed by host-range
      genes. Among the host-range genes: E3L, K3L, and C7L are essential for virus
      replication by preventing interferon resistance, whereas B5R is essential for
      spread of the virus and evasion from the host's immune response as in VACV. We
      report sequence analysis of host-range genes: E3L, K3L, C7L, and membrane protein
      gene (B5R) of BPXVs from buffalo, cattle, and human from recent outbreaks in
      India-their phylogenetic relationship with reference strain (BP4) and other
      Orthopoxviruses. BPXVs revealed a sequence homology with VACVs including zoonotic
      Brazilian VACV-like viruses. The aa sequences of E3L and K3L genes were 100 %
      similar in buffalo, cattle, and human isolates. However, four significant point
      mutations (I11K; N12K and S36F in C7L gene and D249G in B5R gene) were observed
      specific to buffalo isolate only. This signifies that different strains of BPXV
      were circulated during the outbreak. The mutations in C7L and B5R could play an
      important role in adaptation of BPXV in human and cattle which needs further
      functional studies. The strain of BPXV isolated from buffalo may not be adopted
      in human and cow. Various point mutations were observed in the host-range genes
      of reference strain (BPXV-BP4) which may be due to several passages of virus in
      cell culture. The phylogeny constructed based on concatenated gene sequences
      revealed that BPXVs are not as closely related to vaccine strain (Lister and
      Lister-derived strain-LC16m8), as hypothesized earlier, rather they are more
      closely related to reference strain (BPXV-BP4) and other vaccinia and vaccinia
      like viruses such as Passatempo and Aracatuba viruses. The availability of
      information regarding host tropism determinants would allow us to understand
      molecular mechanism of species tropism of poxviruses which would be useful in
      unveiling new strategies to control zoonotic poxviral infections.

PMID- 22872568
TI  - Spinocerebellar ataxias type 8, 12, and 17 and dentatorubro-pallidoluysian
      atrophy in Czech ataxic patients.
AB  - Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative
      disorders currently associated with 27 genes. The most frequent types are caused
      by expansions in coding CAG repeats. The frequency of SCA subtypes varies among
      populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and
      dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where
      the data were missing. We analyzed causal gene expansions in 515 familial and
      sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8
      and SCA17 expansions were identified in eight and five patients, respectively.
      Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and
      the diagnosis of multiple sclerosis (MS) was suspected in two other patients with
      SCA8 expansions. These findings are probably coincidental, although the
      participation of SCA8 expansions in the susceptibility to MS and disease
      progression cannot be fully excluded. None of the patients had pathogenic SCA12
      or DRPLA expansions. However, three patients had intermediate SCA12 alleles out
      of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was
      probable in the patient with 43 CAGs. This coincidence is remarkable, especially
      in the context with the recently identified predisposing role of longer SCA2
      alleles in ALS. Five families with SCA17 represent a significant portion of
      ataxic patients and this should be reflected in the diagnostics of SCAs in the
      Czech population. SCA8 expansions must be considered after careful clinical
      evaluation.

PMID- 22872569
TI  - Is a liberal transfusion strategy better than a symptomatic strategy in patients
      with cardiovascular disease undergoing surgical hip fracture repair?

PMID- 22872571
TI  - Effect of fluoride on insulin level of rats and insulin receptor expression in
      the MC3T3-E1 cells.
AB  - Studies on the role of insulin and insulin receptor (InsR) in the process of
      skeletal fluorosis, especially in osteogenic function, are rare. We evaluated the
      effect of increasing F- doses on the marker of bone formation, serum insulin
      level and pancreatic secretion changes in vivo and mRNA expression of InsR and
      osteocalcin (OCN) in vitro. Wistar rats (n = 50) were divided into two groups,
      i.e. a control group and fluoride group. The fluoride groups were treated with
      fluoride by drinking tap water containing 100 mg F-/L. The fluoride ion-selective
      electrode measured the fluoride concentrations of femurs. The alkaline
      phosphatase (ALP), OCN, insulin and glucagon of serum were tested to observe the
      effect of fluoride action on them. Meantime, the pancreas pathological
      morphometry analysis via beta cells stained by aldehyde fuchsin showed the action
      of fluoride on pancreas secretion. MC3T3-E1 cells (derived from newborn mouse
      calvaria) were exposed to varying concentrations and periods of fluoride. The
      mRNA expression of InsR and OCN was quantified with real-time PCR. Results showed
      that 1-year fluoride treatment obviously stimulated ALP activity and OCN level
      along with increase of bone fluoride concentration of rats, which indicated that
      fluoride obviously stimulated osteogenic action of rats. In vitro study, the dual
      effect of fluoride on osteoblast function is shown. On the other hand, there was
      a significant increase of serum insulin level and a general decrease of glucagon
      level, and the histomorphometry analysis indicated an elevated insulin-positive
      area and increase in islet size in rats treated with fluoride for 1 year. In
      addition, fluoride obviously facilitated the mRNA expression of InsR in vitro. To
      sum up, there existed a close relationship between insulin secretion and fluoride
      treatment. The insulin signal pathway might be involved in the underlying
      occurrence or development of skeletal fluorosis.

PMID- 22872572
TI  - Individual patient-specific immunity against high-grade glioma after vaccination
      with autologous tumor derived peptides bound to the 96 KD chaperone protein.
AB  - PURPOSE: Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant
      treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells
      carry tumor-specific antigenic proteins and can facilitate adaptive and innate
      immune responses. Here we show that peptides bound to a 96 kD chaperone protein
      (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used
      to safely immunize patients with recurrent GBM. EXPERIMENTAL DESIGN:
      Multimodality immunomonitoring was completed on 12 patients with recurrent GBM
      before and after immunization with an autologous HSPPC vaccine derived from
      surgically resected tumor. Clinical endpoints included safety assessments and
      overall survival. RESULTS: No adverse events attributable to the vaccine were
      found. Testing of peripheral blood leukocytes before and after vaccination
      revealed a significant peripheral immune response specific for the peptides bound
      to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders
      after vaccination revealed focal CD4, CD8, and CD56 IFNgamma positive cell
      infiltrates, consistent with tumor site specific immune responses. Immune
      responders had a median survival of 47 weeks after surgery and vaccination,
      compared with 16 weeks for the single nonresponder. CONCLUSIONS: These data
      provide the first evidence in humans of individual patient-specific immune
      responses against autologous tumor derived peptides bound to HSP-96.

PMID- 22872573
TI  - Genome-wide association study of prognosis in advanced non-small cell lung cancer
      patients receiving platinum-based chemotherapy.
AB  - PURPOSE: Genetic variation may influence chemotherapy response and overall
      survival in cancer patients. EXPERIMENTAL DESIGN: We conducted a genome-wide scan
      in 535 advanced-stage non-small cell lung cancer (NSCLC) patients from two
      independent cohorts (307 from Nanjing and 228 from Beijing). A replication was
      carried out on an independent cohort of 340 patients from Southeastern China
      followed by a second validation on 409 patients from the Massachusetts General
      Hospital (Boston, MA). RESULTS: Consistent associations with NSCLC survival were
      identified for five single-nucleotide polymorphisms (SNP) in Chinese populations
      with P values ranging from 3.63 * 10(-5) to 4.19 * 10(-7) in the additive genetic
      model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1,
      and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2
      (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC
      survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3
      (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population.
      CONCLUSION: In this three-stage genome-wide association studies, we identified
      five SNPs as markers for survival of advanced-stage NSCLC patients treated with
      first-line platinum-based chemotherapy in Chinese Han populations. Two of these
      SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian
      patients.

PMID- 22872574
TI  - Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in
      faithful murine cancer models.
AB  - PURPOSE: Anticancer drug development is inefficient, but genetically engineered
      murine models (GEMM) and orthotopic, syngeneic transplants (OST) of cancer may
      offer advantages to in vitro and xenograft systems. EXPERIMENTAL DESIGN: We
      assessed the activity of 16 treatment regimens in a RAS-driven, Ink4a/Arf
      deficient melanoma GEMM. In addition, we tested a subset of treatment regimens in
      three breast cancer models representing distinct breast cancer subtypes: claudin
      low (T11 OST), basal-like (C3-TAg GEMM), and luminal B (MMTV-Neu GEMM). RESULTS:
      Like human RAS-mutant melanoma, the melanoma GEMM was refractory to chemotherapy
      and single-agent small molecule therapies. Combined treatment with AZD6244
      [mitogen-activated protein-extracellular signal-regulated kinase kinase (MEK)
      inhibitor] and BEZ235 [dual phosphoinositide-3 kinase (PI3K)/mammalian target of
      rapamycin (mTOR) inhibitor] was the only treatment regimen to exhibit significant
      antitumor activity, showed by marked tumor regression and improved survival.
      Given the surprising activity of the "AZD/BEZ" combination in the melanoma GEMM,
      we next tested this regimen in the "claudin-low" breast cancer model that shares
      gene expression features with melanoma. The AZD/BEZ regimen also exhibited
      significant activity in this model, leading us to testing in even more diverse
      GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly
      active in these distinct breast cancer models, showing equal or greater efficacy
      compared with any other regimen tested in studies of over 700 tumor-bearing mice.
      This regimen even exhibited activity in lapatinib-resistant HER2(+) tumors.
      CONCLUSION: These results show the use of credentialed murine models for large
      scale efficacy testing of diverse anticancer regimens and predict that
      combinations of PI3K/mTOR and MEK inhibitors will show antitumor activity in a
      wide range of human malignancies.

PMID- 22872575
TI  - Phase I studies of sirolimus alone or in combination with pharmacokinetic
      modulators in advanced cancer patients.
AB  - PURPOSE: Sirolimus is the eponymous inhibitor of the mTOR; however, only its
      analogs have been approved as cancer therapies. Nevertheless, sirolimus is
      readily available, has been well studied in organ transplant patients, and shows
      efficacy in several preclinical cancer models. EXPERIMENTAL DESIGN: Three
      simultaneously conducted phase I studies in advanced cancer patients used an
      adaptive escalation design to find the dose of oral, weekly sirolimus alone or in
      combination with either ketoconazole or grapefruit juice that achieves similar
      blood concentrations as its intravenously administered and approved prodrug,
      temsirolimus. In addition, the effect of sirolimus on inhibition of p70S6 kinase
      phosphorylation in peripheral T cells was determined. RESULTS: Collectively, the
      three studies enrolled 138 subjects. The most commonly observed toxicities were
      hyperglycemia, hyperlipidemia, and lymphopenia in 52%, 43%, and 41% of subjects,
      respectively. The target sirolimus area under the concentration curve (AUC) of
      3,810 ng-h/mL was achieved at sirolimus doses of 90, 16, and 25 mg in the
      sirolimus alone, sirolimus plus ketoconazole, and sirolimus plus grapefruit juice
      studies, respectively. Ketoconazole and grapefruit juice increased sirolimus AUC
      approximately 500% and 350%, respectively. Inhibition of p70 S6 kinase
      phosphorylation was observed at all doses of sirolimus and correlated with blood
      concentrations. One partial response was observed in a patient with epithelioid
      hemangioendothelioma. CONCLUSION: Sirolimus can be feasibly administered orally,
      once weekly with a similar toxicity and pharmacokinetic profile compared with
      other mTOR inhibitors and warrants further evaluation in studies of its
      comparative effectiveness relative to recently approved sirolimus analogs.

PMID- 22872576
TI  - Filamin A is a regulator of blood-testis barrier assembly during postnatal
      development in the rat testis.
AB  - The blood-testis barrier (BTB) is an important ultrastructure in the testis. A
      delay in its assembly during postnatal development leads to meiotic arrest. Also,
      a disruption of the BTB by toxicants in adult rats leads to a failure in
      spermatogonial differentiation. However, the regulation of BTB assembly remains
      unknown. Herein, filamin A, an actin filament cross-linker that is known to
      maintain and regulate cytoskeleton structure and function in other epithelia, was
      shown to be highly expressed during the assembly of Sertoli cell BTB in vitro and
      postnatal development of BTB in vivo, perhaps being used to maintain the actin
      filament network at the BTB. A knockdown of filamin A by RNA interference was
      found to partially perturb the Sertoli cell tight junction (TJ) permeability
      barrier both in vitro and in vivo. Interestingly, this down-regulating effect on
      the TJ barrier function after the knockdown of filamin A was associated with a
      mis-localization of both TJ and basal ectoplasmic specialization proteins.
      Filamin A knockdown also induced a disorganization of the actin filament network
      in Sertoli cells in vitro and in vivo. Collectively, these findings illustrate
      that filamin A regulates BTB assembly by recruiting these proteins to the
      microenvironment in the seminiferous epithelium to serve as the building blocks.
      In short, filamin A participates in BTB assembly by regulating protein
      recruitment during postnatal development in the rat testis.

PMID- 22872578
TI  - Lipopolysaccharide-induced fever depends on prostaglandin E2 production
      specifically in brain endothelial cells.
AB  - Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other
      centrally elicited disease symptoms. The production of PGE2 depends on
      cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the
      identity of the cells involved has been a matter of controversy. We generated
      mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic
      origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile
      response to lipopolysaccharide, associated with elevated levels of PGE2 in the
      cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in
      hematopoietic cells, although displaying elevated PGE2 levels in plasma but not
      in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide,
      thus pointing to the critical role of brain-derived PGE2 for fever.
      Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in
      the brain exclusively occurred in endothelial cells, and quantitative PCR
      analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is
      induced in endothelial cells and not in vascular wall macrophages. Similar
      analysis on liver cells showed induced expression in macrophages and not in
      endothelial cells, pointing at the distinct role for brain endothelial cells in
      PGE2 synthesis. These results identify the brain endothelial cells as the PGE2
      producing cells critical for immune-induced fever.

PMID- 22872577
TI  - Mullerian inhibiting substance recruits ALK3 to regulate Leydig cell
      differentiation.
AB  - Mullerian inhibiting substance (MIS) not only induces Mullerian duct regression
      during male sexual differentiation but also modulates Leydig cell steroidogenic
      capacity and differentiation. MIS actions are mediated through a complex of
      homologous receptors: a type II ligand-binding receptor [MIS type II receptor
      (MISRII)] and a tissue-specific type I receptor that initiates downstream
      signaling. The putative MIS type I receptors responsible for Mullerian duct
      regression are activin A type II receptor, type I [Acvr1/activin receptor-like
      kinase 2 (ALK2)], ALK3, and ALK6, but the one recruited by MIS in Leydig cells is
      unknown. To identify whether ALK3 is the specific type I receptor partner for
      MISRII in Leydig cells, we generated Leydig cell-specific ALK3 conditional
      knockout mice using a Cre-lox system and compared gene expression and
      steroidogenic capacity in Leydig cells of ALK3(fx/fx)Cyp17(cre+) and control mice
      (ALK3(fx/fx)Cyp17(cre-) or ALK3(fx/wt)Cyp17(cre-) littermates). We found reduced
      mRNA expression of the genes encoding P450c17, StAR, and two enzymes (17betaHSD
      III and 3betaHSD-VI) that are expressed in differentiated adult Leydig cells and
      increased expression of androgen-metabolizing enzymes (3alpha-HSD and SRD5A2) and
      proliferating cell nuclear antigen (PCNA) in Leydig cells of
      ALK3(fx/fx)Cyp17(cre+) mice. Despite down-regulation of steroidogenic capacity in
      ALK3(fx/fx)Cyp17(cre+) mice, the loss of MIS signaling also stimulates Leydig
      cell proliferation such that plasma testosterone and androstenedione
      concentrations are comparable to that of control mice. Collectively, these
      results indicate that the phenotype in ALK3 conditional knockout mice is similar
      to that of the MIS-knockout mice, confirming that ALK3 is the primary type I
      receptor recruited by the MIS-MISRII complex during Leydig cell differentiation.

PMID- 22872579
TI  - GPRC6A mediates the effects of L-arginine on insulin secretion in mouse
      pancreatic islets.
AB  - L-arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism
      whereby it stimulates insulin secretion from beta-cells is not known. The
      possibility that l-Arg regulates insulin secretion through a G protein-coupled
      receptor (GPCR)-mediated mechanism is suggested by the high expression of the
      nutrient receptor GPCR family C group 6 member A (GPRC6A) in the pancreas and TC
      6 beta-cells and the finding that Gprc6a(-/]minus]) mice have abnormalities in
      glucose homeostasis. To test the direct role of GPRC6A in regulating insulin
      secretion, we evaluated the response of pancreatic islets derived from Gprc6a(
      /]minus]) mice to L-Arg. We found that the islet size and insulin content were
      decreased in pancreatic islets from Gprac6a(-/]minus]) mice. These alterations
      were selective for beta-cells, because there were no abnormalities in serum
      glucagon levels or glucagon content of islets derived from Gprac6a(-/]minus])
      mice. Significant reduction was observed in both the pancreatic ERK response to L
      Arg administration to Gprc6a(-/]minus]) mice in vivo and L-Arg-induced insulin
      secretion and production ex vivo in islets isolated from Gprc6a(-/]minus]) mice.
      L-Arg stimulation of cAMP accumulation in isolated islets isolated from Gprc6a(
      /]minus]) mice was also diminished. These findings suggest that l-Arg stimulation
      of insulin secretion in beta-cells is mediated, at least in part, through GPRC6A
      activation of cAMP pathways.

PMID- 22872580
TI  - Isolation of marine bacteria with antimicrobial activities from cultured and
      field-collected soft corals.
AB  - Bacteria associated with eight field-collected and five cultured soft corals of
      Briareum sp., Sinularia sp., Sarcophyton sp., Nephtheidae sp., and Lobophytum sp.
      were screened for their abilities in producing antimicrobial metabolites. Field
      collected coral samples were collected from Nanwan Bay in southern Taiwan.
      Cultured corals were collected from the cultivating tank at National Museum of
      Marine Biology and Aquarium. A total of 1,526 and 1,138 culturable, heterotrophic
      bacteria were isolated from wild and cultured corals, respectively; seawater
      requirement and antimicrobial activity were then assessed. There is no
      significant difference between the ratio of seawater-requiring bacteria on the
      wild and cultured corals. The ratio of antibiotic-producing bacteria within the
      seawater-requiring bacteria did not differ between the corals. Nineteen bacterial
      strains that showed high antimicrobial activity were selected for 16S rDNA
      sequencing. Three strains could be assigned at the family level
      (Rhodobacteraceae). The remaining 16 strains belong to eight genera:
      Marinobacterium (2 strains), Pseudoalteromonas (1), Vibrio (5), Enterovibrio (1),
      Tateyamaria (1), Labrenzia (2), and Pseudovibrio (4). The crude extract from
      bacteria strains CGH2XX was found to have high cytotoxicity against the cancer
      cell line HL-60 (IC(50) = 0.94 MUg/ml) and CCRF-CEM (IC(50) = 1.19 MUg/ml). Our
      results demonstrate that the marine bacteria from corals have great potential in
      the discovery of useful medical molecules.

PMID- 22872581
TI  - Response bias in recognition memory as a cognitive trait.
AB  - According to signal detection theory, old-new recognition decisions can be
      affected by response bias, a general proclivity to respond either "old" or "new."
      In recognition experiments, response bias is usually analyzed at a group level,
      but substantial individual differences in bias can underlie group means. These
      differences suggest that, independent of any experimental manipulation, some
      people require more memory evidence than do others before they are willing to
      call an item "old." In four experiments, we investigated the possibility that
      recognition response bias is a partial function of a trait-like predisposition.
      Bias was highly correlated across two recognition study-test cycles separated by
      10 min (Experiment 1). A nearly identical correlation was observed when the tasks
      were separated by one week (Experiment 2). Bias correlations remained significant
      even when the stimuli differed sharply between the first and second study-test
      cycles (Experiment 3). No relationship was detected between bias and response
      strategies in two general knowledge tests (Experiments 2 and 4), but bias did
      weakly predict frequency of false recall in the Deese/Roediger-McDermott (DRM)
      paradigm (Experiment 4). This evidence of trait-like stability suggests an
      entirely different aspect of response bias than that studied by examining its
      modulation by task variables, one for which complete theories of recognition
      memory may need to account.

PMID- 22872582
TI  - How low is low? Low self-esteem as an indicator of internalizing psychopathology
      in adolescence.
AB  - Schools are among the most important setting for preventive interventions among
      adolescents. There are evidence-based intervention programs for adolescents at
      risk for and with early signs of mental health problems but one demanding task is
      to detect the ones who are in need of an intervention. The aim of the present
      study was to analyze associations between self-esteem, depressive symptoms, and
      social anxiety in order to determine clinically relevant cut-points for male and
      female adolescents' self-esteem as measured with the Rosenberg Self-Esteem Scale
      (RSES). The participants of the present prospective study, started in 2002-2003,
      were 2070 adolescents aged 15 years (1,167 girls and 903 boys) at two study sites
      in Finland who participated at both baseline and 2-year follow-up. Self-esteem
      was related to depressive symptoms and social anxiety, and the RSES was able to
      discriminate between cases of depression and social phobia. The present study
      suggests a cutoff of 25 points to classify low self-esteem in both girls and
      boys. Low self-esteem may function as an indicator of various forms of
      internalizing psychopathology. The RSES is worth further examination as a
      potential screening tool for adolescents in risk of psychopathology. 

PMID- 22872583
TI  - Making healthy behaviors the easy choice for employees: a review of the
      literature on environmental and policy changes in worksite health promotion.
AB  - As employers look for ways to reduce rising health care costs, worksite health
      promotion interventions are increasingly being used to improve employee health
      behaviors. An alternative approach to traditional worksite health promotion
      programs is the implementation of environmental and/or policy changes to
      encourage employees to adopt healthier behaviors. This review examines the
      evidence for the effectiveness of worksite health promotion programs using
      environmental and/or policy changes either alone or in combination with
      individually focused health behavior change strategies. A review of the relevant
      literature, published between 1995 and 2010, identified 27 studies that met all
      inclusion criteria. Limited evidence was found for the effectiveness of
      environmental and/or policy changes alone (n = 11) to change employee behavior,
      but more promising results were identified with multicomponent interventions (n =
      16). There is a strong need for improvement in the design and evaluation of
      future health promotion programs focusing solely on environmental and/or policy
      changes at the worksite.

PMID- 22872584
TI  - Application of breast ultrasound in a mammography-based Chinese breast screening
      study.
AB  - We evaluated the clinical significance of the combined use of mammography +
      ultrasound as a new breast screening strategy. The inclusion criteria were: (1)
      females aged >40yrs; (2) breast cancer diagnosis by the breast image screening
      personnel at FUSCC; (3) screening by both ultrasound and mammography; (4)
      mammographic/sonographic images analyzed independently by different radiologists;
      and (5) follow-up for at least 1 year. Fifty-four women were enrolled. The
      analysis included diagnostic sensitivity of mammography, ultrasound, and
      mammography + ultrasound. The sensitivities of mammography and mammography +
      ultrasound were compared overall as well as among different age groups/breast
      densities. The screening sensitivity of mammography, ultrasound, and mammography
      + ultrasound was 79.6, 57.4, and 92.6 %, respectively. The difference between
      mammography and mammography + ultrasound was significant (P < 0.05). The benefit
      of including ultrasound with mammography as a new breast image screening strategy
      was found statistically significant in patients with dense breast on mammogram
      while it was non-significant in younger (<50 years) women. We, therefore,
      concluded that mammography + ultrasound increased the diagnostic sensitivity of
      breast screening; hence it was more desirable for women with dense breast on
      mammography.

PMID- 22872585
TI  - The diagnostic value of treadmill exercise test parameters for coronary artery
      disease.
AB  - The aim of this study was to determine the diagnostic value of treadmill exercise
      test (TET) in patients with coronary heart disease (CHD) by comparing the
      diagnostic conclusions with coronary angiography (CAG). Patients (445) with CHD
      and suspected CHD underwent TET and CAG, and the corresponding diagnostic
      conclusions were compared. (1) Out of the 200 cases that had the positive result
      with TET, 150 cases had been diagnosed CHD by means of CAG; Out of the 245 cases
      that had the negative result during TET, only 39 cases had been diagnosed CHD by
      means of CAG. The sensitivity, specificity, positive predictive value, negative
      predictive value, the false positive incidence, the false negative incidence, and
      agreement rate in diagnosis of CHD by TET were 79.36, 80.40, 75.00, 84.08, 25.00,
      15.92, and 80.00 %, respectively. The patients with multi-vessel disease had a
      higher positive rate of TET as compared with those with single-vessel disease (P
      < 0.05). (2) The parameters for 189 cases positive CAG (patients diagnosed CHD by
      CAG) and 256 cases negative CAG (the control group), including the general
      exercise time, peak heart rate, and the beginning time of ST depression, were
      lower than that of control group (P < 0.05). However, the extent of ST depression
      and duration of ST depression were higher in these patients than in the control
      group (P < 0.05). (3) 189 cases positive CAG, include 87 cases of single coronary
      artery and 102 cases of binary or more coronary arteries (the control group). The
      parameters, including the general exercise time, peak heart rate, and the
      beginning time of ST depression, were lower than the control group (P < 0.05).
      However, the extent of ST depression and duration of ST depression were higher in
      these patients than the control group (P < 0.05). The TET is valuable for
      noninvasive diagnosis of CHD, especially for patients with multi-vessel disease.

PMID- 22872586
TI  - Regional cerebral blood flow in patients with carbon monoxide intoxication.
AB  - RATIONALE AND OBJECTIVES: Early detection of regional cerebral anomalies in acute
      carbon monoxide (CO) poisoning by (99m)Tc-hexamethylprophylene amine oxime
      (HMPAO) brain single photon emission computed tomography (SPECT) imaging has been
      reported previously. However, SPECT findings varied in these studies because of
      their small population sizes. In this study, we included 96 patients with acute
      CO intoxication and analyzed the regional perfusion changes in these patients by
      means of HMPAO brain SPECT. MATERIALS AND METHODS: Ninety-six patients, aged 4-80
      years (mean age 32 years) with acute CO intoxication diagnosed by our emergency
      department were included in this study. Exclusion criteria included previous
      cerebrovascular diseases, brain injury, brain surgery and any known neurological
      and psychological disorders. All patients underwent a brain scan using a dual
      head camera and fan-beam collimator 90-120 min after injection of (99m)Tc-HMPAO.
      Brain SPECT images were obtained for interpretation. RESULTS: Our data suggested
      that 79 of the 96 patients (82.3 %) had abnormal HMPAO brain images. The
      predominant site of disease was basal ganglia (52/96 = 54.2 %), followed by
      temporal lobe (48/96 = 50.0 %), parietal lobe (44/96 = 45.8 %), frontal lobe
      (30/96 = 31.2 %), occipital lobe (21/96 = 21.9 %) and thalamus (8/96 = 8.3 %). No
      patients with acute CO intoxication had perfusion abnormalities in the
      cerebellum. In addition, there was no significant difference in serum COHb levels
      between patients with abnormal and normal HMPAO brain images. CONCLUSION: (99m)Tc
      HMPAO SPECT imaging is a useful tool to detect functional brain injury in acute
      CO intoxication.

PMID- 22872587
TI  - Structure elucidation and inhibitory effects on NO production of clerodane
      diterpenes from Ajuga decumbens.
AB  - Three new clerodane diterpenes (1-3), together with five known analogues (4-8),
      have been isolated from the whole plants of Ajuga decumbens. Their structures
      were established by detailed spectroscopic and spectrometric data analyses (IR,
      ESIMS, HR-ESIMS, 1D and 2D NMR). The inhibitory activities of these diterpenes on
      LPS-induced NO production were evaluated, and compounds 1-4 and 6-8 showed
      inhibitory effects.

PMID- 22872588
TI  - Acylated iridoids from the roots of Valeriana officinalis var. latifolia.
AB  - Phytochemical investigation of the roots of Valeriana officinalis var. latifolia
      resulted in the isolation and characterization of six new acylated iridoids,
      (5S,7S,8S,9S)-7-hydroxy-8-isovaleroyloxy-Delta4,11-dihyronepetalactone (1),
      (5S,7S,8S,9S)-7-hydroxy-10-isovaleroyloxy-Delta4,11-dihyronepetalactone (2),
      (5S,8S,9S)-10-isovaleroyloxy-Delta4,11-dihyronepetalactone (3), (5S,6S,8S,9R)-6
      isovaleroyloxy-Delta4,11-1,3-diol (4), (5S,6S,8S,9R)-1,3-isovaleroxy-Delta4,11
      1,3-diol (5), and (5S,6S,8S,9R)-3-isovaleroxy-6-isovaleroyloxy-Delta4,11-1,3-diol
      (6). Their structures were determined mainly by 1D and 2D NMR spectroscopic
      techniques. We also report herein for the first time the single crystal X-ray
      structure of compound 1. In addition, the cytotoxic activities of compounds 1-6
      were evaluated against A549 (human lung adenocarcinoma), HCT116 (human colon
      carcinoma), SK-BR-3 (human breast carcinoma), and HepG2 (human hepatoma) cell
      lines. Compound 6 showed weak cell growth inhibition of A549, HCT116, SK-BR-3,
      and HepG2 cells.

PMID- 22872589
TI  - Blockade of the renin-angiotensin system with delphinidin, cyanin, and quercetin.
AB  - Overactivation of the renin-angiotensin system is one of the most important risk
      factors for the development of hypertension. The use of the crude extracts and/or
      active compounds, such as anthocyanins and quercetin, of herbal plants that have
      antihypertensive effects is beneficial for decreasing of blood pressure level.
      However, the molecular mechanisms by which anthocyanins (delphinidin and cyanin)
      and quercetin regulate the renin-angiotensin system are not completely
      understood. In this study, we demonstrate that delphinidin, cyanin, and quercetin
      interrupt the renin-angiotensin system signaling pathway by inhibiting the
      angiotensin-converting enzyme activity and decreasing its mRNA production.
      Furthermore, treatment with either delphinidin or cyanin significantly inhibited
      renin mRNA production. However, delphinidin, cyanin, and quercetin did not act as
      the angiotensin II type 1 receptor antagonist and did not play roles in the
      regulation of its internalization. The direct inhibition of components of the
      renin-angiotensin system advances our understanding of the antihypertensive
      effects of these compounds.

PMID- 22872590
TI  - Effect of long-term administration of cordycepin from Cordyceps militaris on
      testicular function in middle-aged rats.
AB  - This study was carried out to examine the potential beneficial effect of
      cordycepin on the decline of testicular function induced with age. A total of 30
      male Sprague-Dawley rats (twenty-four 12-month-olds and six 2-month-olds) were
      divided into five groups. The young control (YC) and middle-aged control (MC)
      groups received vehicle only. Cordycepin-treated groups were administered daily
      doses of oral cordycepin at 5, 10, and 20 mg/kg body weight for 4 months. As a
      result, the MC group exhibited epididymal weight loss, decreased sperm motility,
      and reduced spermatogenesis compared to the young control group. Interestingly,
      the epididymal weights of middle-aged rats were dose-dependently increased by
      treatment with cordycepin. Cordycepin also improved calcium levels and decreased
      urea and nitrogen, uric acid, and creatinine in the blood of middle-aged rats. In
      addition, cordycepin significantly increased sperm motility and the
      progressiveness of sperm movement. All cordycepin-treated groups showed well
      arranged spermatogonia, densely packed cellular material, and increased numbers
      of mature spermatozoa in the seminiferous lumen compared to the middle-aged
      control group. These results indicate that long-term administration of cordycepin
      can counteract the decline of testicular function in middle-aged rats.

PMID- 22872591
TI  - Positive interaction of thyme (red) essential oil with human polymorphonuclear
      granulocytes in eradicating intracellular Candida albicans.
AB  - The essential oils have started to be recognized for their potential
      antimicrobial role only in recent years. Clinical experience showed that the
      efficacy of antimicrobial agents depends not only on their direct effect on a
      given microorganism but also on the functional activity of the host immune
      system. Since data on the effects of essential oils on the innate immune system
      are scanty and fragmentary, the aim of this study was to evaluate the influence
      of thyme (red) essential oil (EO), at subinhibitory/inhibitory concentrations, on
      intracellular killing activity by human polymorphonuclear granulocytes (PMNs)
      against Candida albicans. In order to provide a frame of reference for the
      activity of this EO, its in vitro killing activity in the absence of PMNs was
      also evaluated.Results showed that EO at subminimal inhibitory (subMIC)/minimal
      inhibitory (MIC) concentrations significantly enhanced intracellular killing of
      C. albicans in comparison with EO-free controls and was comparable to the
      positive control (fluconazole). In in vitro killing assays without PMNs, we
      observed progressive growth of the yeast cells in the presence of EO subMIC/MIC
      concentrations. A positive antifungal interaction with phagocytes could explain
      why this EO, which appeared to be only fungistatic in time-kill assays, had
      efficacy in killing yeast cells once incubated with PMNs.

PMID- 22872592
TI  - Platycodin D inhibits lipogenesis through AMPKalpha-PPARgamma2 in 3T3-L1 cells
      and modulates fat accumulation in obese mice.
AB  - Platycodin D (PD) has been reported to control obesity in vivo. This study
      investigated the molecular mechanism of PD, focusing on its ability to decrease
      the expression of adipogenic factors through AMP-activated protein kinase alpha
      (AMPKalpha) in adipocytes and its ability to prevent abdominal fat accumulation
      in high-fat diet-induced obese C57BL/6 mice. The inhibitory effect of lipid
      accumulation in 3T3-L1 cells was measured by Oil Red O staining, reverse
      transcription-polymerase chain reaction (RT-PCR), and Western blotting. To
      determine the antiobesity effect in vivo, one group of mice were given a normal
      diet and the others were fed a high-fat diet for 8 weeks. The high-fat diet mice
      were then assigned to one of three subgroups: aminoimidazole carboxamide
      ribonucleotide (AICAR), vehicle, and PD. PD significantly reduced fat
      accumulation by inhibiting adipogenic signal transcriptional factors, such as
      peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT/enhancer
      binding protein alpha (C/EBPalpha), which functions via AMPK signaling, in vitro.
      PD reduced both body weight and fat volume; consequently, lipid metabolism was
      improved by increasing AMPKalpha, similar to AICAR, and reduced PPARgamma2 and
      C/EBPalpha expression in adipose tissue. The results suggested that PD could be
      used to decrease the expression of adipogenic factors related to the AMPK
      pathway. Hence, PD could be an alternative treatment for controlling obesity by
      downregulating lipid accumulation.

PMID- 22872594
TI  - [Quality of life for adolescents with vocal cord dysfunction].
AB  - BACKGROUND: Vocal cord dysfunction (VCD) is a functional breathing disorder. A
      psychosomatic aetiology has been discussed and associations with depression,
      anxiety disorders, and social stress have been reported. We have undertaken a
      screening of behavioural and emotional problems in adolescent patients using
      standardised questionnaires. METHODS: Thirty-one patients (8 - 16 years) with the
      clinical suspicion of VCD were investigated using the Youth-Self-Report (YSR/11 -
      18) and for the assessment of the parents we used the analoguous Child-Behaviour
      Checklist (CBCL/6 - 18). YSR and CBCL contain two sub-areas: (a) competence
      scales that measure the child's participation in activities, social skills and
      school achievements and (b) items that contain subscales for emotional problems
      such as depressive and anxiety symptoms, conduct problems such as oppositional
      defiant problems and aggressive behaviour, social problems and physical
      complaints. RESULTS: On average, the features of VCD patients were not
      significantly different from those of the reference population. But we did
      observe tendencies of psychological problems (YSR 16.7 %, CBCL 20 %) compared
      with the standard (2 %) in the syndrome scales of both questionnaires Adolescents
      reported particularly more internalising disorders such as social retreat,
      physical complaint and anxiety and depressive symptoms. The parents reported more
      often "physical complaints" (13.3 %) and "aggressive behaviour" (10 %).
      CONCLUSIONS: We found tendencies of psychological strain, mainly social retreat,
      physical complaints and anxiety and depressive symptoms. Further investigations
      should focus on those emotional problems as well as on psychosomatically caused
      physical problems. Personality and psychological stress of the parents should be
      included in the investigation in order to evaluate the reports of the parents on
      higher aggressive behaviour and enhanced physical problems of their children in
      relation to their own psychological strain. We suggest family therapies, family
      counselling, or parental coaching as a therapeutic approach.

PMID- 22872593
TI  - Statin therapy and clinical outcomes in myocardial infarction patients
      complicated by acute heart failure: insights from the EPHESUS trial.
AB  - AIMS: Several clinical trials have shown that in patients with acute myocardial
      infarction (MI), statin therapy improves cardiovascular (CV) outcomes, but in
      these trials patients with acute heart failure (HF) were excluded or only a few
      were included. In patients with chronic HF, statin therapy does not reduce all
      cause or CV mortality. We aimed to assess the association between statin therapy
      and clinical outcomes in the setting of acute HF with systolic dysfunction
      complicating acute MI. METHODS AND RESULTS: We performed a post-hoc analysis in
      6632 patients included in the EPHESUS trial. The mean age of patients was 64
      years and 71% were male. Overall, 47% of patients had a statin prescribed at
      baseline. Cox regression models and a secondary analysis using propensity score
      matching were fit to assess the association between statin prescription and
      clinical outcomes. During a mean follow-up of 16 +/- 7 months, all-cause death
      occurred in 385 (12%) patients with and in 647 (18%) patients without a statin (P
      < 0.001). After extensive adjustment, the risk of all-cause death was 20% lower
      in patients on statin [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69
      0.92, P = 0.001]. This positive association was mostly due to a lower risk of CV
      death (HR 0.76, 95% CI 0.65-0.88, P = 0.0002). In contrast, statin use was
      associated with a higher risk of non-CV hospitalizations (HR 1.16, 95% CI 1.02
      1.33, P = 0.02). CONCLUSION: Our results suggest that patients with acute HF
      complicating acute MI may benefit from being on statin therapy. Prospective
      clinical trials are required to validate these findings.

PMID- 22872595
TI  - Non-communicable diseases: harnessing the current opportunities.
AB  - Non-communicable diseases (NCDs) are receiving growing attention, which brings a
      unique opportunity to utilise solutions available to address them. These diseases
      are largely preventable; proven, cost-effective interventions are available; and
      when NCDs emerge, means exist to treat them, prevent complications, and to
      improve quality of life. Yet, there is a lack in progress in responding
      effectively to NCDs, and the current discussion and research focus predominantly
      on challenges rather than the opportunities, which this paper outlines.

PMID- 22872596
TI  - Referral from primary to secondary care in Germany: developing a taxonomy based
      on cluster analysis.
AB  - AIMS: Referrals from primary to secondary care may differ regarding motivation
      and initiative. Previous research on the frequency and variation of referrals has
      mostly treated referrals as homogeneous. We intended to develop a taxonomy
      regarding referrals from primary to secondary care in Germany that could support
      decision making on a macro level. METHODS: We analyzed 3,988 referrals by 29
      German general practitioners (GPs). GPs were asked to document all referrals
      during one week; in subsequent audits they stated the reasons and initiative for
      any referral. We postulated the following five referral types: clinical problem,
      shared care, administrative, patient initiated and shared cost. The data were
      analyzed with k-means cluster analysis. RESULTS: We identified three of our five
      postulated referral types with cluster analytic techniques: shared care, clinical
      problem, and patient initiated. This solution accounted for 11.7% of total
      variance. The majority of referrals in German primary care practices were
      initiated by the GP, or they were part of a shared decision with patients.
      CONCLUSIONS: We suggest a taxonomy of referrals that might offer insights
      regarding the allocation of resources within the German health system. Referrals
      might be reduced by improved training of primary care physicians and by giving
      them more competencies in routine care of chronic patients.

PMID- 22872597
TI  - The confidence in health care and social services in northern Sweden--a
      comparison between reindeer-herding Sami and the non-Sami majority population.
AB  - AIMS: To investigate the confidence in primary health care, psychiatry and social
      services among the reindeer-herding Sami and the non-Sami population of northern
      Sweden. METHODS: A semi-randomized, cross-sectional study design comprising 325
      reindeer-herding Sami (171 men, 154 women) and a control population of 1,437 non
      Sami (684 men, 753 women). A questionnaire on the confidence in primary health
      care, psychiatry, social services, and work colleagues was distributed to members
      of reindeer-herding families through the Sami communities and to the control
      population through the post. The relative risk for poor confidence was analyzed
      by calculating odds ratios with 95% confidence intervals adjusted for age and
      level of education. RESULTS: The confidence in primary health care and psychiatry
      was significantly lower among the reindeer-herding Sami compared with the control
      group. No differences were found between men and women in the reindeer-herding
      Sami population. In both the reindeer-herding Sami and the control population,
      younger people (<= 48 years) reported significantly lower confidence in primary
      health care than older individuals (>48 years). CONCLUSIONS: A conceivable reason
      for the poor confidence in health care organizations reported by the reindeer
      herding Sami is that they experience health care staff as poorly informed about
      reindeer husbandry and Sami culture, resulting in unsuitable or unrealistic
      treatment suggestions. The findings suggest that the poor confidence constitutes
      a significant obstacle of the reindeer-herding Sami to fully benefit from public
      health care services.

PMID- 22872598
TI  - GPs' prescription routines and cooperation with other healthcare personnel before
      and after implementation of multidose drug dispensing.
AB  - BACKGROUND: This study addresses GPs' attitudes towards multidose drug dispensing
      before and after implementation and their perceived experience of how multidose
      drug dispensing affects prescription and communication routines for patients in
      the home care services. This study contributes to a method triangulation with two
      other studies on the introduction of multidose drug dispensing in Trondheim.
      METHODS: A controlled before-and-after study carried out in Trondheim
      (intervention) and Tromso (control). A questionnaire was distributed to all GPs
      in the two towns in 2005 with a follow-up questionnaire in 2008. RESULTS: The GPs
      in Trondheim showed a positive attitude to multidose drug dispensing both before
      and after the implementation. Increased workload was reported, but still the GPs
      wanted the system to be continued. Most of the GPs reported a better overview of
      the patients' medication and a supposed reduction in medication errors. The GPs'
      prescription- and communication routines were changed only for the multidose drug
      users and not for the other patients in the home care services. CONCLUSIONS: The
      study supports the results presented in two previous publications according to
      GPs' positive attitude towards multidose drug dispensing, their better overview
      of the patients' medications, and improved cooperation with the pharmacy. This
      study adds to our understanding of prescription routines among GPs and the use of
      the medication module in the electronic health record.

PMID- 22872599
TI  - Weapons used in serious violence against a parent: retrospective comparative
      register study.
AB  - AIMS: Our aim was to compare the weapons used in lethal or potentially lethal
      violence against parents according to the age (adolescent vs. adult) of the
      offender and victim (mother vs. father) of the offence. METHOD: All forensic
      psychiatric examination statements of male offenders who had offended violently
      against one of their parents during 1973-2004 in Finland (n=192) were reviewed
      retrospectively. Data on the weapons used by adolescent and adult offenders in
      relation to the sex of the victim, mental disorder, criminal responsibility and
      intelligence were gathered. RESULTS: In the whole sample, sharp-edged weapons
      were the most commonly used weapons. Firearms were more commonly used in offences
      against fathers (i.e. patricidal offences) than against mothers (i.e. matricidal
      offences). Adolescent offenders were more likely to use firearms than adult
      offenders in violent acts against a parent. Among personality-disordered
      subjects, patricidal offenders used firearms more commonly than did matricidal
      offenders. Homicidal matricidal offenders had higher full-scale and verbal IQ
      scores as compared to homicidal patricidal offenders. The matricidal offenders
      using firearms were shown to be more intelligent as measured by full-scale and
      verbal scale IQs than the patricidal offenders using firearms. CONCLUSIONS:
      Consistent with the physical strength hypothesis, firearms are used more often in
      lethal or potentially lethal violence against parents by adolescents than by
      adults in Finland. As firearms legislation in Finland is currently under reform
      the study findings suggest that restriction of gun availability may have an
      influence on intrafamilial homicides, particularly those committed by
      adolescents.

PMID- 22872600
TI  - [Pediatric fracture diagnosis--ultra-low-dose CT with an effective dose equal to
      that of radiographs].
AB  - PURPOSE: Computed tomography (CT) plays an important role in trauma diagnosis in
      children, especially for complex fractures. The aim of this study was to examine
      the diagnostic value of ultra-low-dose-CT (ULD-CT) with an effective dose equal
      to that of radiographs in an experimental study and to compare its results with
      those of radiographs. MATERIALS AND METHODS: Limb bones of dead young pigs served
      as a model for pediatric bones. A total of 51 fractured and non-fractured bones
      were examined with a 64 multislice-CT with a standard dose protocol as gold
      standard, with two ultra-low-dose-protocols, and with standard radiographs with
      different exposures. RESULTS: In spite of high background noise the examinations
      of ULD-CT were not adequate only in 2 of 204 cases. ULD-CT was slightly superior
      to radiographs in detection of fractures. ULD-CT could significantly better
      characterize the fractures than radiographs. The overall result of ULD-CT was
      significantly better than that of radiographs with standard exposure. CONCLUSION:
      ULD-CT with the effective dose of radiographs is successfully applicable in
      pediatric fracture diagnosis, and its overall result is significantly better than
      that of radiographs.

PMID- 22872601
TI  - Lung, liver and lymph node metastases in follow-up MSCT: comprehensive volumetric
      assessment of lesion size changes.
AB  - PURPOSE: To investigate measurement accuracy in terms of precision and inter
      rater variability in the simultaneous volumetric assessment of lung, liver and
      lymph node metastasis size change over time in comparison to RECIST 1.1.
      MATERIALS AND METHODS: Three independent readers evaluated multislice CT data
      from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A
      total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually
      (RECIST 1.1) and by volumetry with semi-automated software. The quality of
      segmentation and need for manual adjustments were recorded. Volumes were
      converted to effective diameters to allow comparison to RECIST. For statistical
      assessment of precision and interobserver agreement, the Wilcoxon-signed rank
      test and Bland-Altman plots were utilized. RESULTS: The quality of segmentation
      after manual correction was acceptable to excellent in 95 % of lesions and manual
      corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph
      nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective)
      relative measurement deviation (p <.001). Inter-reader median variation
      coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for
      different lesion types (p < .001). The limits of agreement were +/- 9.8 to +/-
      11.2 % for volumetric assessment. CONCLUSION: Superior precision and inter-rater
      variability of volumetric over manual measurement of lesion change over time was
      demonstrated in a whole body setting.

PMID- 22872602
TI  - [Minimal-Invasive CT-guided spinal interventions--from pain therapy over biopsies
      to tumor therapy].
AB  - CT-guided spinal interventions have undergone a remarkable evolution during the
      last view years, leading to a wider range of indications, as well as to the
      development of highly specialized new procedures. This review article deals with
      different aspects of spinal CT-guided pain management, biopsy and tumor therapies
      and emphasizes a selection of practical considerations of important
      interventions.

PMID- 22872603
TI  - [Grey-Turner sign in necrotizing pancreatitis].

PMID- 22872604
TI  - [Dispensing with sedation in pediatric MR imaging of the brain: what is
      feasible?].
AB  - PURPOSE: Feasibility study to evaluate whether a diagnostic pediatric MRI scan of
      the brain can be performed without sedation by using BLADE sequences with
      rotating blade-like k-space covering. MATERIALS AND METHODS: Between 01/09 and
      12/10 all children with a planned MRI of the brain were included. After age
      dependent preparation of the child the MRI was acquired with a parent closely
      attending. Pharmacological sedation was only applied when strong motion artifacts
      occurred. All MRI sequences were independently reviewed by 2 radiologists who
      ranked image quality on a scale of III (excellent image quality, no motion
      artefacts), II (motion artefacts but still diagnostic quality), and I (non
      diagnostic image quality). RESULTS: 326 children (53 % male, mean age 7.2 +/- 4.3
      years) were evaluated of whom 247 (76 %) had to be sedated. All infants < 1 year
      and 84 % of 1-year-old patients, 90 % of 2-year-old, 59 % of 3-year-old, 9 % of 4
      year-old children, and 2 % of patients older than 4 years had to be sedated. In
      total, 2461 MRI sequences (7.6 +/- 1.2 per study) including 622 BLADE sequences
      (25 %) were acquired. Reviewer A rated 2077 sequences (84 %) as III, 318 (13 %)
      as II, and 66 (3 %) as I, whereas reviewer B rated 2119 sequences (86 %) as III,
      308 (13 %) as II, and 34 (1 %) as I. Inter-observer agreement was good to
      excellent (normal/weighted kappa value for BLADE sequences: 0.88/0.56, for all
      sequences: 0.92/0.71). CONCLUSION: Age-adjusted preparation and implementation of
      a pediatric cranial MRI may reduce the need for sedation. BLADE sequences abate
      motion artefacts thus enabling acquisition of diagnostic images even in young
      children. In patients older than 3 years, performance of MRI scans without
      sedation should be considered.

PMID- 22872605
TI  - Diathermy-induced ventricular fibrillation with Riata high-voltage lead
      insulation failure.

PMID- 22872606
TI  - Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of
      acute bacterial prostatitis.
AB  - Prostatitis plays a major role in morbidity and mortality related to prostate
      diseases. The aim of this study was to detect whether thymoquinone (TQ) could
      ameliorate oxidative damage and the proliferative response induced by Escherichia
      coli (E. coli) in rats. A total of 42 adult male Wistar rats were used. The rats
      were randomly divided into seven groups (three treatment groups, three infected
      groups and one control group). Control group received saline and was killed 24 h
      after saline administration. Infected rats were killed after 24, 48 and 72 h
      following direct injection of E. coli into the prostate. Treatment groups were
      administered with 10 mg/kg dose of TQ intraperitoneally following E. coli
      injection and after 24 and 48 h following E. coli injection. The rats were killed
      at 24, 48 and 72 h after the first drug administration. Each group was compared
      with each other and with the control group. In addition, infected groups were
      compared with treatment groups. Our findings show that the treatment with TQ has
      a protective effect against bacterial prostatitis-induced tissue injury. Increase
      in malondialdehyde levels and histological damage caused by E. coli were improved
      markedly with TQ treatment. TQ treatment particularly increased the activity of
      glutathione peroxidase and decreased the activities of catalase and superoxide
      dismutase. These observations might be attributed, at least in part, to the
      antioxidant effect of TQ and suggest that it could be a clinically valuable agent
      in the prevention of acute prostatitis caused by E. coli.

PMID- 22872607
TI  - AKRs expression in peripheral blood lymphocytes from smokers: the role of body
      mass index.
AB  - Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including
      polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and
      reactive oxygen species (ROS), which are capable of initiating and promoting
      carcinogenesis. Exposure to PAHs, their metabolites, and ROS further increase
      AKRs isoform expression that may amplify oxidative damage. Human AKR enzymes are
      highly polymorphic, and allelic variants may contribute to different AKRs
      expression in individuals. Despite the importance of AKRs in PAHs metabolism,
      there are no studies that evaluate, in general human populations, the effect of
      PAHs on AKRs expression in peripheral blood lymphocytes (PBLs). The aim of this
      study was to determine the effect of tobacco smoke exposure, and AKR1A1*2 and
      AKR1C3*2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels
      in PBLs from smokers. In the smoker group, there is a statistically significant
      positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine
      cotinine levels in individuals with a body mass index (BMI) less than 25.
      However, AKR1A1*2 and AKR1C3*2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3
      mRNA levels. These results suggest that AKRs induction by PAHs in smokers' PBLs
      is associated with BMI; therefore, the role of adipose tissue accumulation in
      PAHs' effects needs further investigation.

PMID- 22872608
TI  - Tadalafil in pulmonary hypertension: may be more than seen?

PMID- 22872609
TI  - Sonographic detection of breast microcalcifications - technically feasible and
      clinically relevant?

PMID- 22872610
TI  - [The scientific representation of the mid-sized sections and study groups of
      DEGUM at the Dreilandertreffen, Mainz 2010].

PMID- 22872612
TI  - Farmers urged to be vigilant for signs of acute SBV infection.

PMID- 22872613
TI  - Equine athletes get the best veterinary care at London 2012.

PMID- 22872615
TI  - VBF fellowships for 'extraordinary' care.

PMID- 22872616
TI  - RCVS Audit and Risk Committee: members appointed.

PMID- 22872617
TI  - National award for excellence in teaching.

PMID- 22872621
TI  - Developing a working partnership for animal health and welfare.

PMID- 22872623
TI  - Fetal deformities detected during surveillance for Schmallenberg virus.

PMID- 22872624
TI  - Air quality, subclinical disease and animal production losses.

PMID- 22872625
TI  - A scientifically based profession?

PMID- 22872626
TI  - Government support in understanding Schmallenberg virus.

PMID- 22872627
TI  - 'Bovine bunions': an additional hypothesis for the pathogenesis of sole ulcers.

PMID- 22872628
TI  - Hereditary ataxia, myokymia and neuromyotonia in Jack Russell terriers.

PMID- 22872629
TI  - Recognising exceptional contributions of veterinary surgeons.

PMID- 22872632
TI  - Toxic effects of heavy metals (Cd, Cr and Pb) on seed germination and growth and
      DPPH-scavenging activity in Brassica rapa var. turnip.
AB  - Toxicity of heavy metal is a wide spread environmental problem affecting all life
      forms including plants. In the present study the toxic effects of heavy metals,
      cadmium (Cd), chromium (Cr) and lead (Pb) on seed germination rate (%),
      germination index (G-index) and growth (mm) of Brassica rapa var. turnip have
      been investigated. The seeds were soaked either in distilled water (control) or
      in aqueous solutions of Cd, Cr and Pb (1 g/l, 2.5 g/l and 5 g/l) at 4 degrees C
      in dark for 24 hours. Prior to inoculation onto MS0 medium, the soaked seeds were
      either washed with sterile distilled water or inoculated without washing on
      solidified MS0 medium at 25 +/- 2 degrees C with 16/8-hour photoperiod in a
      growth chamber to germinate in vitro. Such stress conditions revealed that by
      increasing the concentration of heavy metals, the germination rate (%), G-index
      value and growth (mm) decreased significantly, suggesting their toxic effect on
      B. rapa var. turnip. This study further revealed that experiment with seed
      washing resulted in less toxicity of selected heavy metals on germination and
      growth of B. rapa var. turnip, as compared to experiment without washing.
      However, the resulting toxicity order of the selected heavy metals remained the
      same (Cd > Cr > Pb). Significant decrease has been observed in seed viability and
      germination potential and finally heavy metals completely ceased further growth
      and development of plants. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging
      activity revealed that significantly higher activity was observed in control
      plants without heavy metals treatment. Furthermore, the Cd-treated plants showed
      decreased antioxidant activity. Cr and Pb were less toxic as compared to Cd
      (control > Pb > Cr > Cd). This study revealed that selected heavy metals not only
      affected plant development but also disturbed plant metabolic pathways. 

PMID- 22872633
TI  - The cytogenetic effects of the aqueous extracts of migratory locust (Locusta
      migratoria L.) in vitro.
AB  - One of the useful and most commonly cultivated commercially species, migratory
      locust (Locusta migratoria; Orthoptera), was investigated in light of genotoxic
      damage potentials. For this aim, we evaluated the genotoxic potentials of water
      soluble extracts of L. migratoria on cultured human blood cells. The
      micronucleus, sister chromatid exchange and structural chromosome aberration
      assays were applied to assess DNA and chromosomal damage produced by aqueous
      extracts in vitro. The extracts were added to the cultures at different
      concentrations ranging from 0 to 1000 mg/L. Our results indicated that these
      extracts did not exhibit genotoxicity at tested concentrations. We conclude that
      this in vitro approach for biomonitoring genotoxicity assessment is useful for
      comparing the potential health risks of edible insects. 

PMID- 22872634
TI  - Characterization of enzymes from Legionella pneumophila involved in reversible
      adenylylation of Rab1 protein.
AB  - After the pathogenic bacterium Legionella pneumophila is phagocytosed, it injects
      more than 250 different proteins into the cytoplasm of host cells to evade
      lysosomal digestion and to replicate inside the host cell. Among these secreted
      proteins is the protein DrrA/SidM, which has been shown to modify Rab1b, a main
      regulator of vesicular trafficking in eukaryotic cells, by transfer of adenosine
      monophosphate (AMP) to Tyr(77). In addition, Legionella provides the protein SidD
      that hydrolytically reverses the covalent modification, suggesting a tight
      spatial and temporal control of Rab1 function by Legionella during infection.
      Small angle x-ray scattering experiments of DrrA allowed us to validate a
      tentative complex model built by combining available crystallographic data. We
      have established the effects of adenylylation on Rab1 interactions and properties
      in a quantitative way. In addition, we have characterized the kinetics of DrrA
      catalyzed adenylylation as well as SidD-catalyzed deadenylylation toward Rab1 and
      have determined the nucleotide specificities of both enzymes. This study enhances
      our knowledge of proteins subverting Rab1 function at the Legionella-containing
      vacuole.

PMID- 22872635
TI  - Replication fork stalling and checkpoint activation by a PKD1 locus mirror repeat
      polypurine-polypyrimidine (Pu-Py) tract.
AB  - DNA sequences prone to forming noncanonical structures (hairpins, triplexes, G
      quadruplexes) cause DNA replication fork stalling, activate DNA damage responses,
      and represent hotspots of genomic instability associated with human disease. The
      88-bp asymmetric polypurine-polypyrimidine (Pu-Py) mirror repeat tract from the
      human polycystic kidney disease (PKD1) intron 21 forms non-B DNA secondary
      structures in vitro. We show that the PKD1 mirror repeat also causes orientation
      dependent fork stalling during replication in vitro and in vivo. When integrated
      alongside the c-myc replicator at an ectopic chromosomal site in the HeLa genome,
      the Pu-Py mirror repeat tract elicits a polar replication fork barrier. Increased
      replication protein A (RPA), Rad9, and ataxia telangiectasia- and Rad3-related
      (ATR) checkpoint protein binding near the mirror repeat sequence suggests that
      the DNA damage response is activated upon replication fork stalling. Moreover,
      the proximal c-myc origin of replication was not required to cause orientation
      dependent checkpoint activation. Cells expressing the replication fork barrier
      display constitutive Chk1 phosphorylation and continued growth, i.e. checkpoint
      adaptation. Excision of the Pu-Py mirror repeat tract abrogates the DNA damage
      response. Adaptation to Chk1 phosphorylation in cells expressing the replication
      fork barrier may allow the accumulation of mutations that would otherwise be
      remediated by the DNA damage response.

PMID- 22872636
TI  - A GxxxG-like motif within HIV-1 fusion peptide is critical to its
      immunosuppressant activity, structure, and interaction with the transmembrane
      domain of the T-cell receptor.
AB  - To thrive in the human body, HIV fuses to its target cell and evades the immune
      response via several mechanisms. The fusion cascade is initiated by the fusion
      peptide (FP), which is located at the N-terminal of gp41, the transmembrane
      protein of HIV. Recently, it has been shown that the HIV-1 FP, particularly its 5
      13 amino acid region (FP(5-13)), suppresses T-cell activation and interacts with
      the transmembrane domain (TMD) of the T-cell receptor (TCR) complex. Specific
      amino acid motifs often contribute to such interactions in TMDs of membrane
      proteins. Using bioinformatics and experimental studies, we report on a GxxxG
      like motif (AxxxG), which is conserved in the FP throughout different clades and
      strains of HIV-1. Biological activity studies and FTIR spectroscopy revealed that
      HIV FP(5-13)-derived peptides, in which the motif was altered either by
      randomization or by a single amino acid shift, lost their immunosuppressive
      activity concomitant with a loss of the beta-sheet structure in a membranous
      environment. Furthermore, fluorescence studies revealed that the inactive mutants
      lost their ability to interact with their target site, namely, the TMD of
      TCRalpha, designated CP. Importantly, lipotechoic acid activated macrophages
      (lacking TCR) were not affected by FP, further demonstrating the specificity of
      the immunosuppressant activity of CP. Finally, although the AxxxG WT and the
      GxxxG analog both associated with the CP and immunosuppressed T-cells, the AxxxG
      WT but not the GxxxG analog induced lipid mixing. Overall, the data support an
      important role for the AxxxG motif in the function of FP and might explain the
      natural selection of the AxxxG motif rather than the classical GxxxG motif in FP.

PMID- 22872637
TI  - A single rainbow trout cobalamin-binding protein stands in for three human
      binders.
AB  - Cobalamin uptake and transport in mammals are mediated by three cobalamin-binding
      proteins: haptocorrin, intrinsic factor, and transcobalamin. The nature of
      cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim
      of this study was to characterize the cobalamin-binding proteins of the rainbow
      trout (Oncorhynchus mykiss) and to compare their properties with those of the
      three human cobalamin-binding proteins. High cobalamin-binding capacity was found
      in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and
      plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based
      on analysis of partial sequences and immunological responses. The trout cobalamin
      binding protein was purified from roe fluid, sequenced, and further
      characterized. Like haptocorrin, the trout cobalamin-binding protein was stable
      at low pH and had a high binding affinity for the cobalamin analog cobinamide.
      Like haptocorrin and transcobalamin, the trout cobalamin-binding protein was
      present in plasma and recognized ligands with altered nucleotide moiety. Like
      intrinsic factors, the trout cobalamin-binding protein was present in the stomach
      and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic
      factor in the composition of conserved residues in the primary cobalamin-binding
      site in the C terminus. The trout cobalamin-binding protein was glycosylated and
      displayed spectral properties comparable with those of haptocorrin and intrinsic
      factor. In conclusion, only one soluble cobalamin-binding protein was identified
      in the rainbow trout, a protein that structurally behaves like an intermediate
      between the three human cobalamin-binding proteins.

PMID- 22872638
TI  - Identification of residues in the C-terminal domain of HIV-1 integrase that
      mediate binding to the transportin-SR2 protein.
AB  - Transportin-SR2 (TRN-SR2 and TNPO3) is a cellular cofactor of HIV replication
      that has been implicated in the nuclear import of HIV. TRN-SR2 was originally
      identified in a yeast two-hybrid screen as an interaction partner of HIV
      integrase (IN) and in two independent siRNA screens as a cofactor of viral
      replication. We have now studied the interaction of TRN-SR2 and HIV IN in
      molecular detail and identified the TRN-SR2 interacting regions of IN. A weak
      interaction with the catalytic core domain (CCD) and a strong interaction with
      the C-terminal domain (CTD) of IN were detected. By dissecting the catalytic core
      domain (CCD) of IN into short structural fragments, we identified a peptide
      (INIP(1), amino acids (170)EHLKTAVQMAVFIHNFKRKGGI(191)) retaining the ability to
      interact with TRN-SR2. By dissecting the C-terminal domain (CTD) of IN, we could
      identify two interacting peptides (amino acids (214)QKQITKIQNFRVYYR(228) and
      (262)RRKVKIIRDYGK(273)) that come together in the CTD tertiary structure to form
      an exposed antiparallel beta-sheet. Through site-specific mutagenesis, we defined
      the following sets of amino acids in IN as important for the interaction with TRN
      SR2: Phe-185/Lys-186/Arg-187/Lys-188 in the CCD and Arg-262/Arg-263/Lys-264 and
      Lys-266/Arg-269 in the CTD. An HIV-1 strain carrying K266A/R269A in IN was
      replication-defective due to a block in reverse transcription, confounding the
      study of nuclear import. Insight into the IN/TRN-SR2 interaction interface is
      necessary to guide drug discovery efforts targeting the nuclear entry step of
      replication.

PMID- 22872639
TI  - Impaired thymic export and increased apoptosis account for regulatory T cell
      defects in patients with non-ST segment elevation acute coronary syndrome.
AB  - Regulatory T (Treg) cells play a protective role against the development of
      atherosclerosis. Previous studies have revealed Treg cell defects in patients
      with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms
      underlying these defects remain unclear. In this study, we found that the numbers
      of peripheral blood CD4(+)CD25(+)CD127(low) Treg cells and
      CD4(+)CD25(+)CD127(low)CD45RA(+)CD45RO(-) naive Treg cells were lower in the
      NSTACS patients than in the chronic stable angina (CSA) and the chest pain
      syndrome (CPS) patients. However, the number of CD4(+)CD25(+)CD127(low)CD45RA(
      )CD45RO(+) memory Treg cells was comparable in all of the groups. The frequency
      of CD4(+)CD25(+)CD127(low)CD45RO(-)CD45RA(+)CD31(+) recent thymic emigrant Treg
      cells and the T cell receptor excision circle content of purified Treg cells were
      lower in the NSTACS patients than in the CSA patients and the CPS controls. The
      spontaneous apoptosis of Treg cells (defined as CD4(+)CD25(+)CD127(low)annexin
      V(+)7-AAD(-)) was increased in the NSTACS patients compared with the CSA and CPS
      groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the
      oxidized LDL levels were significantly higher in the NSTACS patients than in the
      CSA and CPS groups. In accordance with the altered Treg cell levels, the
      concentration of TNF-alpha was increased in the NSTACS patients, resulting in a
      decreased IL-10/TNF-alpha ratio. These findings indicate that the impaired thymic
      output of Treg cells and their enhanced susceptibility to apoptosis in the
      periphery were responsible for Treg cell defects observed in the NSTACS patients.

PMID- 22872640
TI  - Interaction of the HIV-1 intasome with transportin 3 protein (TNPO3 or TRN-SR2).
AB  - Transportin 3 (TNPO3 or TRN-SR2) has been shown to be an important cellular
      factor for early steps of lentiviral replication. However, separate studies have
      implicated distinct mechanisms for TNPO3 either through its interaction with HIV
      1 integrase or capsid. Here we have carried out a detailed biophysical
      characterization of TNPO3 and investigated its interactions with viral proteins.
      Biophysical analyses including circular dichroism, analytical
      ultracentrifugation, small-angle x-ray scattering, and homology modeling provide
      insight into TNPO3 architecture and indicate that it is highly structured and
      exists in a monomer-dimer equilibrium in solution. In vitro biochemical binding
      assays argued against meaningful direct interaction between TNPO3 and the capsid
      cores. Instead, TNPO3 effectively bound to the functional intasome but not to
      naked viral DNA, suggesting that TNPO3 can directly engage the HIV-1 IN tetramer
      prebound to the cognate DNA. Mass spectrometry-based protein footprinting and
      site-directed mutagenesis studies have enabled us to map several interacting
      amino acids in the HIV-1 IN C-terminal domain and the cargo binding domain of
      TNPO3. Our findings provide important information for future genetic analysis to
      better understand the role of TNPO3 and its interacting partners for HIV-1
      replication.

PMID- 22872641
TI  - A novel core fucose-specific lectin from the mushroom Pholiota squarrosa.
AB  - Fucalpha1-6 oligosaccharide has a variety of biological functions and serves as a
      biomarker for hepatocellular carcinoma because of the elevated presence of
      fucosylated alpha-fetoprotein (AFP) in this type of cancer. In this study we
      purified a novel Fucalpha1-6-specific lectin from the mushroom Pholiota squarrosa
      by ion-exchange chromatography and affinity chromatography on thyroglobulin
      agarose. The purified lectin was designated as PhoSL (P. squarrosa lectin). SDS
      PAGE, MALDI-TOF mass spectrometry, and N-terminal amino acid sequencing indicate
      that PhoSL has a molecular mass of 4.5 kDa and consists of 40 amino acids (NH(2)
      APVPVTKLVCDGDTYKCTAYLDFGDGRWVAQWDTNVFHTG-OH). Isoelectric focusing of the lectin
      showed bands near pI 4.0. The lectin activity was stable between pH 2.0 and 11.0
      and at temperatures ranging from 0 to 100  degrees C for incubation times of 30
      min. When PhoSL was investigated with frontal affinity chromatography using 132
      pyridylaminated oligosaccharides, it was found that the lectin binds only to core
      alpha1-6-fucosylated N-glycans and not to other types of fucosylated
      oligosaccharides, such as alpha1-2-, alpha1-3-, and alpha1-4-fucosylated glycans.
      Furthermore, PhoSL bound to alpha1-6-fucosylated AFP but not to non-fucosylated
      AFP. In addition, PhoSL was able to demonstrate the differential expression of
      alpha1-6 fucosylation between primary and metastatic colon cancer tissues. Thus,
      PhoSL will be a promising tool for analyzing the biological functions of alpha1-6
      fucosylation and evaluating Fucalpha1-6 oligosaccharides as cancer biomarkers.

PMID- 22872642
TI  - Evaluation of riproximin binding properties reveals a novel mechanism for
      cellular targeting.
AB  - Riproximin is a cytotoxic type II ribosome-inactivating protein showing high
      selectivity for tumor cell lines. Its binding to cell surface glycans is crucial
      for subsequent internalization and cytotoxicity. In this paper, we describe a
      unique mechanism of interaction and discuss its implications for the cellular
      targeting and cytotoxicity of riproximin. On a carbohydrate microarray,
      riproximin specifically bound to two types of asialo-glycans, namely to bi- and
      triantennary complex N-glycan structures (NA2/NA3) and to repetitive N-acetyl-D
      galactosamine (GalNAc), the so-called clustered Tn antigen, a cancer-specific O
      glycan on mucins. Two glycoproteins showing high riproximin binding, the NA3
      presenting asialofetuin and the clustered Tn-rich asialo-bovine submaxillary
      mucin, were subsequently chosen as model glycoproteins to mimic the binding
      interactions of riproximin with the two types of glycans. ELISA analyses were
      used to relate the two binding specificities of riproximin to its two sugar
      binding sites. The ability of riproximin to cross-link the two model proteins
      revealed that binding of the two types of glycoconjugates occurs within different
      binding sites. The biological implications of these binding properties were
      analyzed in cellular assays. The cytotoxicity of riproximin was found to depend
      on its specific and concomitant interaction with the two glycoconjugates as well
      as on dynamic avidity effects typical for lectins binding to multivalent
      glycoproteins. The presence of definite, cancer-related structures on the cells
      to be targeted determines the therapeutic potency of riproximin. Due to its cross
      linking ability, riproximin is expected to show a high degree of specificity for
      cells exposing both NA2/NA3 and clustered Tn structures.

PMID- 22872643
TI  - Site-specific O-glucosylation of the epidermal growth factor-like (EGF) repeats
      of notch: efficiency of glycosylation is affected by proper folding and amino
      acid sequence of individual EGF repeats.
AB  - O-Glucosylation of epidermal growth factor-like (EGF) repeats in the
      extracellular domain of Notch is essential for Notch function. O-Glucose can be
      elongated by xylose to the trisaccharide, Xylalpha1-3Xylalpha1-3Glcbeta1-O-Ser,
      whose synthesis is catalyzed by the consecutive action of three
      glycosyltransferases. A UDP-glucose:protein O-glucosyltransferase (Poglut/Rumi)
      transfers O-glucose to serine within the O-glucose consensus. Subsequently,
      either of two UDP-xylose:glucoside xylosyltransferases (Gxylt1 or Gxylt2)
      transfers xylose to O-glucose. Finally, a UDP-xylose:xyloside xylosyltransferase
      (Xxylt1) transfers xylose to Xylalpha1-3Glcbeta1-O-EGF. Our prior site-mapping
      studies demonstrated that O-glucose consensus sites are modified at high but
      variable stoichiometries in mouse Notch1 and identified a novel glycosylation
      site with alanine in place of proline, suggesting a revised, broader consensus
      sequence (CXSX(P/A)C). Here we examined the molecular basis for this site
      specificity. A panel of EGF repeats from human coagulation factor 9 (FA9), mouse
      Notch1, and Notch2 were bacterially expressed and purified by reverse phase HPLC
      for use in in vitro enzyme assays. We demonstrate that proper folding of EGF
      repeats is essential for glycosylation by Poglut/Rumi, that alanine can
      substitute for proline in the context of coagulation factor 9 EGF repeat for O
      glucose transfer, confirming the new consensus sequence, and that positively
      charged residues within the O-glucose consensus sequence reduce efficiency of
      glycosylation by Poglut/Rumi. Moreover, proper folding of EGF repeats is also
      important for the activities of Gxylt1, Gxylt2, and Xxylt1. These results
      indicate that protein folding and amino acid sequences of individual EGF repeats
      fundamentally affect both attachment and elongation of O-glucose glycans.

PMID- 22872644
TI  - Fibrils colocalize caspase-3 with procaspase-3 to foster maturation.
AB  - Most proteases are expressed as inactive precursors, or zymogens, that become
      activated by limited proteolysis. We previously identified a small molecule,
      termed 1541, that dramatically promotes the maturation of the zymogen, procaspase
      3, to its mature form, caspase-3. Surprisingly, compound 1541 self-assembles into
      nanofibrils, and localization of procaspase-3 to the fibrils promotes activation.
      Here, we interrogate the biochemical mechanism of procaspase-3 activation on 1541
      fibrils in addition to proteogenic amyloid-beta(1-40) fibrils. In contrast to
      previous reports, we find no evidence that procaspase-3 alone is capable of self
      activation, consistent with its fate-determining role in executing apoptosis. In
      fact, mature caspase-3 is >10(7)-fold more active than procaspase-3, making this
      proenzyme a remarkably inactive zymogen. However, we also show that fibril
      induced colocalization of trace amounts of caspase-3 or other initiator proteases
      with procaspase-3 dramatically stimulates maturation of the proenzyme in vitro.
      Thus, similar to known cellular signaling complexes, these synthetic or natural
      fibrils can serve as platforms to concentrate procaspase-3 for trans-activation
      by upstream proteases.

PMID- 22872645
TI  - Photo-induced regulation of the chromatic adaptive gene expression by Anabaena
      sensory rhodopsin.
AB  - Rhodopsin molecules are photochemically reactive membrane-embedded proteins, with
      seven transmembrane alpha-helices, which bind the chromophore retinal (vitamin A
      aldehyde). They are roughly divided into two groups according to their basic
      functions: (i) ion transporters such as proton pumps, chloride pumps, and cation
      channels; and (ii) photo-sensors such as sensory rhodopsin from microbes and
      visual pigments from animals. Anabaena sensory rhodopsin (ASR), found in 2003 in
      the cyanobacterium Anabaena PCC7120, is categorized as a microbial sensory
      rhodopsin. To investigate the function of ASR in vivo, ASR and the promoter
      sequence of the pigment protein phycocyanin were co-introduced into Escherichia
      coli cells with the reporter gene crp. The result clearly showed that ASR
      functions as a repressor of the CRP protein expression and that this is fully
      inhibited by the light activation of ASR, suggesting that ASR would directly
      regulate the transcription of crp. The repression is also clearly inhibited by
      the truncation of the C-terminal region of ASR, or mutations on the C-terminal
      Arg residues, indicating the functional importance of the C-terminal region.
      Thus, our results demonstrate a novel function of rhodopsin molecules and raise
      the possibility that the membrane-spanning protein ASR could work as a
      transcriptional factor. In the future, the ASR activity could be utilized as a
      tool for arbitrary protein expression in vivo regulated by visible light.

PMID- 22872646
TI  - TRIM50 protein regulates vesicular trafficking for acid secretion in gastric
      parietal cells.
AB  - Of the TRIM/RBCC family proteins taking part in a variety of cellular processes,
      TRIM50 is a stomach-specific member with no defined biological function. Our
      biochemical data demonstrated that TRIM50 is specifically expressed in gastric
      parietal cells and is predominantly localized in the tubulovesicular and
      canalicular membranes. In cultured cells ectopically expressing GFP-TRIM50,
      confocal microscopic imaging revealed dynamic movement of TRIM50-associated
      vesicles in a phosphoinositide 3-kinase-dependent manner. A protein overlay assay
      detected preferential binding of the PRY-SPRY domain from the TRIM50 C-terminal
      region to phosphatidylinositol species, suggesting that TRIM50 is involved in
      vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids.
      Trim50 knock-out mice retained normal histology in the gastric mucosa but
      exhibited impaired secretion of gastric acid. In response to histamine, Trim50
      knock-out parietal cells generated deranged canaliculi, swollen microvilli
      lacking actin filaments, and excess multilamellar membrane complexes. Therefore,
      TRIM50 seems to play an essential role in tubulovesicular dynamics, promoting the
      formation of sophisticated canaliculi and microvilli during acid secretion in
      parietal cells.

PMID- 22872647
TI  - A 96-week randomized trial of switching to entecavir in chronic hepatitis B
      patients with a partial virological response to lamivudine.
AB  - BACKGROUND: Growing numbers of chronic hepatitis B (CHB) patients in the Asia
      Pacific region have failed first-line therapy with low genetic barrier drugs.
      This prospective, 96-week study investigated the antiviral efficacy, safety and
      tolerability of switching to entecavir versus maintaining lamivudine in CHB
      patients with a partial virological response to lamivudine. METHODS: A total of
      72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA>=60 IU/ml
      after >=6 months lamivudine monotherapy were randomized 1:1 to receive either
      entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. RESULTS: Mean duration
      of prior lamivudine treatment was 15.1 months in the lamivudine-maintained
      patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV
      DNA levels of 4.66 and 4.55 log(10) IU/ml, respectively. A greater proportion of
      entecavir-switch than lamivudine-maintained patients achieved undetectable HBV
      DNA at all time points (67.6% versus 11.4% at week 96; P<0.001). Entecavir-switch
      patients achieved a greater mean decrease in HBV DNA level by week 4, maintained
      through week 96. Entecavir-switch patients with baseline HBV DNA<5 log(10) IU/ml
      were more likely to achieve a virological response at week 96. A total of 6
      (17.6%) entecavir-switch and 2 (5.7%) lamivudine-maintained patients achieved
      HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved
      HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged
      in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir
      switch patients after 96 weeks. CONCLUSIONS: Switching to entecavir in patients
      with a partial virological response to lamivudine resulted in increased
      virological efficacy and lower rates of antiviral resistance than maintaining
      lamivudine.

PMID- 22872648
TI  - A randomized controlled trial of sequential pegylated interferon-alpha and
      telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic
      hepatitis B.
AB  - BACKGROUND: Short-term treatment for hepatitis B e antigen (HBeAg)-negative
      chronic hepatitis B remains unsatisfactory. The aim of our study was to compare
      the efficacy and safety of two sequential regimens of pegylated interferon (PEG
      IFN)-alpha and telbivudine (LdT). METHODS: Adult patients with biopsy-proven
      HBeAg-negative chronic hepatitis B, elevated alanine aminotransferase (ALT) and
      serum HBV DNA >= 2,000 IU/ml were randomized 1:1 at baseline to receive PEG-IFN
      180 MUg/week for 24 weeks followed by LdT 600 mg/day for 24 weeks (PEG-IFN
      first), or vice versa (LdT first), plus 24-week follow-up; individuals with HCV,
      HDV or HIV coinfections and lamivudine resistance were excluded. Primary end
      points were serum HBV DNA<2,000 IU/ml and normal ALT at week 72. RESULTS: A total
      of 30 patients (86% male, median age 48 years) were enrolled: mean +/-sd baseline
      serum HBV DNA was 5.56 +/- 1.4 log IU/ml and ALT was 2.9 +/- 2.5* upper limit of
      normal. At end of follow-up (week 72), HBV DNA<2,000 IU/ml was achieved in 13.3%
      of participants in the PEG-IFN first group versus 46.7% of those in the LdT first
      group (P=0.046). Mean +/-sd ALT levels were significantly lower in the LdT first
      group (1.3 +/- 0.9 versus 3.2 +/- 2.7* upper limit of normal; P=0.03). PEG-IFN
      dose was reduced in 2 (7%) patients and 1 (7%) patient dropped out due to
      myalgia. CONCLUSIONS: Sequential treatment with 24 weeks PEG-IFN followed or
      preceded by 24 weeks of LdT is safe. Virological response rate at week 72 was
      significantly higher in patients treated with LdT followed by PEG-IFN than vice
      versa. A sequential antiviral regimen of LdT followed by PEG-IFN, if confirmed in
      larger series, could improve response rates compared with standard PEG-IFN
      monotherapy.

PMID- 22872649
TI  - Clinical and virological response to entecavir in HBV-related chronic hepatitis
      or cirrhosis: data from the clinical practice in a single-centre cohort.
AB  - BACKGROUND: Limited data are available on entecavir in Caucasian patients with
      HBV cirrhosis or chronic hepatitis B who are treated in the clinical practice.
      The aim was to evaluate the efficacy of entecavir in an Italian cohort of
      unselected patients with different stages of liver fibrosis, comparing the
      virological and clinical results obtained between patients with and without liver
      cirrhosis. METHODS: Efficacy and safety of entecavir were retrospectively
      evaluated in 100 patients recruited in the Gastro-Hepatology Unit, San Giovanni
      Battista Hospital (Turin, Italy). A pharmacokinetic analysis was performed in 34
      participants to assess whether cirrhosis may affect entecavir metabolism.
      Participants were followed-up for a median (range) duration of 21 months (2-108).
      RESULTS: Rates of virological response (negative viraemia by PCR for >= 2
      consecutive determinations) after 12, 24 and 36 months were 91.7%, 97.5% and
      93.7%, respectively. In the 84 patients who were treated for >= 12 months,
      presence of cirrhosis (OR 1.730, 95% CI 1.082, 2.766; P=0.022) and absence of
      hepatitis B e antigen (OR 0.479, 95% CI 0.273, 0.842; P=0.011) were independent
      predictors of earlier clearance of serum HBV DNA. There were no differences
      between the serum concentrations in the steady-state level of entecavir between
      patients with or without cirrhosis. No significant differences were detected
      between the average area under the curve in the means of the two groups (P=0.55).
      CONCLUSIONS: Entecavir represents an excellent therapy in patients with HBV
      related liver disease and particularly with cirrhosis where it showed a good
      profile of tolerability, higher efficacy and an earlier virological response.

PMID- 22872655
TI  - Towards a bio-inspired leg design for high-speed running.
AB  - High-speed terrestrial locomotion inevitably involves high acceleration and
      extensive loadings on the legs. This imposes a challenging trade-off between
      weight and strength in leg design. This paper introduces a new design paradigm
      for a robotic leg inspired by musculoskeletal structures. The central hypothesis
      is that employing a tendon-bone co-location architecture not only provides
      compliance in the leg, but can also reduce bone stresses caused by bending on
      structures. This hypothesis is applied to a leg design, and verified by
      simulations and the experiments on a prototype. In addition, we also present an
      optimization scheme to maximize the strength to weight ratio. Using the tendon
      bone co-location architecture, the stress on the bone during a stride is reduced
      by up to 59%. A new foam-core prototyping technique enables creating structural
      characteristics similar to mammalian bones in the robotic leg. This method allows
      us to use lighter polymeric structures that are cheaper and quicker to fabricate
      than conventional fabrication methods, and can eventually greatly shorten the
      design iteration cycle time.

PMID- 22872656
TI  - Peripheral chemoreceptors mediate training-induced plasticity in paraventricular
      nucleus pre-autonomic oxytocinergic neurons.
AB  - We showed previously that sino-aortic denervation prevented training-induced
      plasticity in pre-autonomic oxytocinergic neurons and blocked the beneficial
      effects of training. In this study, we investigate the combined effect of
      training and removal of specific chemoreceptor afferents on both cardiovascular
      parameters and oxytocin (OT) gene and protein expression within the hypothalamic
      paraventricular nucleus (PVN). Wistar rats and spontaneously hypertensive rats
      (SHRs) underwent carotid body denervation or sham surgery and were trained or
      kept sedentary for 3 months. After haemodynamic measurements at rest, rats were
      anaesthetized for brain perfusion. Fresh (perfused with PBS) and fixed brains
      (perfused with 4% paraformaldehyde) were processed for PVN OT mRNA (real-time
      PCR) and OT immunoreactivity within PVN subnuclei. In sham-operated rats,
      training improved treadmill performance and reduced resting heart rate (Wistar, 
      8%; SHRs, -10%), with a reduction in blood pressure only in SHRs (-8%). Training
      was accompanied by increased PVN OT mRNA expression (twofold increase in sham
      operated SHRs) and peptide density in the posterior, ventromedial and dorsal cap
      PVN subnuclei (on average 70% increase in both strains), with significant
      correlations between OT content and training-induced resting bradycardia in sham
      operated groups. Carotid body denervation did not interfere with the performance
      gain, abolished chemoreflex activation (without changing baroreflex control) and
      blocked training-induced cardiovascular adaptations and training-induced changes
      in PVN OT content in both strains. After carotid body denervation, there was no
      correlation between OT mRNA or OT immunoractivity and resting heart rate. The
      chronic absence of chemoreceptor inputs uncovers an unknown role of chemoreceptor
      signalling in driving the plasticity/activity of PVN oxytocinergic pre-autonomic
      neurons, thus mediating training-induced cardiovascular adaptive responses.

PMID- 22872657
TI  - Sweat loss during heat stress contributes to subsequent reductions in lower-body
      negative pressure tolerance.
AB  - The contribution of sweating to heat stress-induced reductions in haemorrhagic
      tolerance is not known. This study tested the hypothesis that fluid loss due to
      sweating contributes to reductions in simulated haemorrhagic tolerance in
      conditions of heat stress. Eight subjects (35 +/- 8 years old; 77 +/- 5 kg)
      underwent a normothermic time control and two heat stress trials (randomized).
      The two heat stress trials were as follows: (i) with slow intravenous infusion of
      lactated Ringer solution sufficient to offset sweat loss (IV trial); or (ii)
      without intravenous infusion (dehydration; DEH trial). Haemorrhage was simulated
      via progressive lower-body negative pressure (LBNP) to presyncope after core body
      (intestinal) temperature was raised by ~1.5  degrees C using a water-perfused
      suit or a normothermic time control period. The LBNP tolerance was quantified via
      a cumulative stress index. Middle cerebral artery blood velocity (transcranial
      Doppler) and mean blood pressure (Finometer(r)) were measured continuously.
      Relative changes in plasma volume were calculated from haematocrit and
      haemoglobin. Increases in core body temperature and sweat loss (~1.6% body mass
      deficit) were similar (P > 0.05) between heat stress trials. Slow intravenous
      infusion (1.2 +/- 0.3 litres) prevented heat-induced reductions in plasma volume
      (IV trial, -0.6 +/- 6.1%; and DEH trial, -6.6 +/- 5.1%; P = 0.01). Intravenous
      infusion improved LBNP tolerance (632 +/- 64 mmHg min) by ~20% when compared with
      the DEH trial (407 +/- 117 mmHg min; P = 0.01), yet tolerance remained 44% lower
      in the IV trial relative to the time control normothermic trial (1138 +/- 183
      mmHg min; P < 0.01). These data indicate that although sweat-induced dehydration
      impairs simulated haemorrhagic tolerance, this impairment is secondary to the
      negative impact of heat stress itself.

PMID- 22872658
TI  - Postexercise hypotension and sustained postexercise vasodilatation: what happens
      after we exercise?
AB  - A single bout of aerobic exercise produces a postexercise hypotension associated
      with a sustained postexercise vasodilatation of the previously exercised muscle.
      Work over the last few years has determined key pathways for the obligatory
      components of postexercise hypotension and sustained postexercise vasodilatation
      and points the way to possible benefits that may result from these robust
      responses. During the exercise recovery period, the combination of centrally
      mediated decreases in sympathetic nerve activity with a reduced signal
      transduction from sympathetic nerve activation into vasoconstriction, as well as
      local vasodilator mechanisms, contributes to the fall in arterial blood pressure
      seen after exercise. Important findings from recent studies include the
      recognition that skeletal muscle afferents may play a primary role in
      postexercise resetting of the baroreflex via discrete receptor changes within the
      nucleus tractus solitarii and that sustained postexercise vasodilatation of the
      previously active skeletal muscle is primarily the result of histamine H(1) and
      H(2) receptor activation. Future research directions include further exploration
      of the potential benefits of these changes in the longer term adaptations
      associated with exercise training, as well as investigation of how the recovery
      from exercise may provide windows of opportunity for targeted interventions in
      patients with hypertension and diabetes.

PMID- 22872659
TI  - Is there a nitrergic modulation of the rat external anal sphincter?
AB  - Nitric oxide is known to relax the internal anal sphincter, but its effect on the
      external anal sphincter (EAS) is unknown. The aim of this study was to
      investigate whether there is a nitrergic nerve plexus that modulates the EAS,
      similar to that found in oesophageal striated muscle. An in vitro ring
      preparation of rat anal canal was used to evaluate the effects of the nitric
      oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) and the NO donor
      sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and
      the effect of SNP on nerve-evoked contractions. Immunohistological experiments
      were conducted to determine whether the neuronal isoform of nitric oxide synthase
      (nNOS) is present in the EAS. During direct muscle stimulation neither L-NNA (P =
      0.32) nor SNP (P = 0.19) significantly changed the EF(50), which is the frequency
      at which 50% of maximal contraction is reached, compared with a time-dependent
      control. Nerve-evoked contractions were also not altered by addition of SNP to
      the tissue bath. Immunohistohistological experiments clearly showed co
      localization of nNOS-positive nerve fibres at motor endplates of the oesophagus
      but not in the EAS. The internal anal sphincter was richly innervated by
      nitrergic fibres, but these did not extend into the EAS. In conclusion, there are
      no nitrergic motor fibres innervating the EAS, neurotransmission at the motor
      endplates is not affected by NO, and NO does not affect muscle force directly in
      conditions of neuromuscular blockade. There is, therefore, no evidence that EAS
      contraction is directly modulated by NO or by pudendal nitrergic fibres or
      diffusion from neighbouring nitrergic plexuses of the anal canal.

PMID- 22872660
TI  - Role of the parasympathetic nervous system in cardioprotection by remote hindlimb
      ischaemic preconditioning.
AB  - This investigation was designed to determine the participation of the vagus nerve
      and muscarinic receptors in the remote ischaemic preconditioning (rIPC)
      mechanism. New Zealand rabbits were anaesthetized, and the femoral artery was
      dissected. After 30 min of monitoring, the hearts were isolated and subjected to
      30 min of global no-flow ischaemia and 180 min of reperfusion (non-rIPC group).
      The ventricular function was evaluated, considering the left ventricular
      developed pressure and the left ventricular end-diastolic pressure. In the rIPC
      group, the rabbits were subjected to three cycles of hindlimb ischaemia (5 min)
      and reperfusion (5 min), and the same protocol as that used in non-rIPC group was
      then repeated. In order to evaluate the afferent neural pathway during the rIPC
      protocol we used two groups, one in which the femoral and sciatic nerves were
      sectioned and the other in which the spinal cord was sectioned (T9-T10 level). To
      study the efferent neural pathway during the rIPC protocol, the vagus nerve was
      sectioned and, in another group, atropine was administered. The effect of vagal
      stimulation was also evaluated. An infarct size of 40.8 +/- 3.1% was obtained in
      the non-rIPC group, whereas in rIPC group the infarct size decreased to 16.4 +/-
      3.5% (P < 0.05). During the preconditioning protocol, the vagus nerve section and
      the atropine administration each abolished the effect of rIPC on infarct size.
      Vagal stimulation mimicked the effect of rIPC, decreasing infarct size to 15.2 +/
      4.7% (P < 0.05). Decreases in infarct size were accompanied by improved left
      ventricular function. We demonstrated the presence of a neural afferent pathway,
      because the spinal cord section completely abolished the effect of rIPC on
      infarct size. In conclusion, rIPC activates a neural afferent pathway, the
      cardioprotective signal reaches the heart through the vagus nerve (efferent
      pathway), and acetylcholine activates the ischaemic preconditioning phenomenon
      when acting on the muscarinic receptors.

PMID- 22872661
TI  - The role of Cl- in the regulation of ion and liquid transport in the intact
      alveolus during beta-adrenergic stimulation.
AB  - The epithelium of the developing lung displays an evolving liquid transport
      phenotype, in which Cl(-) secretion during fetal life is rapidly switched to
      Na(+) absorption perinatally. However, the mechanisms underlying the homeostasis
      of the thin layer of liquid lining the postnatal pulmonary epithelium remain
      elusive. In particular, it remains unclear whether the stimulated clearance of
      excess alveolar liquid is mediated via transepithelial Cl(-) transport. Our study
      is a pharmacological analysis with the aim of addressing this issue, which is of
      major physiological significance in cases of pulmonary oedema from any cause. We
      measured the rate of transepithelial liquid movement (J(v)) with (125)I-albumin,
      in the in situ perfused adult rat lung. Transepithelial Cl(-) transport was
      studied with the use of the Cl(-) channel inhibitor NPPB in the resting state and
      during stimulation with the beta(2)-adrenergic agonist terbutaline. The study of
      J(v) in these conditions revealed the following findings: (1) there is net
      absorption of excess of alveolar liquid in the resting, unstimulated state, which
      is predominantly amiloride sensitive; (2) inhibition of Cl(-) transport with NPPB
      in the resting state results in a 1.6-fold increase in net absorption of alveolar
      liquid; and (3) the terbutaline-stimulated net absorption of the excess liquid is
      enhanced by 2.8-fold in the presence of NPPB. Our results are suggestive of the
      functional presence of secretory, but not absorptive, Cl(-) mechanisms and show
      that transepithelial Cl(-) transport is not part of the mechanism underlying lung
      liquid clearance in response to beta-adrenergic stimulation.

PMID- 22872662
TI  - Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic
      outflow and blood pressure.
AB  - Central melanocortin 3/4 receptors (MC3/4Rs) are known to regulate energy
      balance. Activation of MC3/4Rs causes a greater increase in the firing activity
      of the PVN neurons in obese Zucker rats than in lean Zucker rats. The present
      study was undertaken to determine the roles of MC3/4Rs in the hypothalamic
      paraventricular nucleus (PVN) in modulating the sympathetic activity and blood
      pressure and its downstream pathway. Renal sympathetic nerve activity (RSNA) and
      mean arterial pressure (MAP) were recorded in anaesthetized rats. Microinjection
      of the MC3/4R agonist melanotan II (MTII) into the PVN increased the RSNA and
      MAP. The MC3/4R antagonist agouti-related peptide (AgRP) or SHU9119 decreased the
      RSNA and MAP, but the MC4R antagonist HS024 had no significant effect on the RSNA
      and MAP. The effects of MTII were abolished by pretreatment of the PVN with AgRP,
      SHU9119, the adenylate cyclase inhibitor SQ22536 or the protein kinase A
      inhibitor Rp-cAMP, and substantially attenuated by HS024. Microinjection of
      SQ22536 alone into the PVN had no significant effect on the RSNA and MAP, but Rp
      cAMP caused significant decreases in the RSNA and MAP. Furthermore, MTII
      increased the cAMP level in the PVN. These results indicate that activation of
      MC3/4Rs in the PVN increases the sympathetic outflow and blood pressure via the
      cAMP-protein kinase A pathway. Melanocortin 3 receptors in the PVN may exert a
      tonic excitatory effect on sympathetic activity.

PMID- 22872663
TI  - Evaluation of pleural-based nodules in a 52-year-old woman with a history of
      metastatic breast cancer.

PMID- 22872664
TI  - The presence of sodium nitrate in generator eluate decreases the radiochemical
      purity of 99mTc-sestamibi.
AB  - A high radiochemical purity (RCP) is recommended for radiopharmaceutical
      compounds used in the clinical practice of nuclear medicine. However, some
      preparations of (99m)Tc-sestamibi contain excess impurities (>6%). To understand
      the origin of these impurities, we investigated the effect of sodium nitrate on
      the RCP of sestamibi preparations by testing eluates from 3 commercially
      available (99m)Tc generators. METHODS: The sestamibi kits (Stamicis) were
      reconstituted with (99m)Tc eluate from nitrate-containing wet-column (NCWC),
      nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators.
      Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was
      determined using aluminum oxide sheets as the stationary phase and absolute
      ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine,
      albumin nanocolloid, and soluble albumin were also tested for their RCP values
      with eluates from the 3 different (99m)Tc generators. RESULTS: The RCP assessment
      of (99m)Tc-sestamibi was performed on 127 Stamicis preparations. Significantly
      lower RCP values were found for Stamicis kits prepared with the NCWC generator
      than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001)
      generators. The number of Stamicis preparations with an RCP under 94% was greater
      with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC
      (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration
      of nitrate in NFWC generator eluates significantly decreased the RCP of the
      Stamicis preparation. In the absence of nitrate in (99m)Tc eluate, no difference
      was observed between the RCP values of Stamicis kits prepared with the NFWC and
      NFDC generators. The (99m)Tc impurities generated by nitrates did not modify the
      quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because
      these impurities are not in the heart field of view. No other tested (99m)Tc
      radiopharmaceutical interfered with nitrates. CONCLUSION: We recommend using
      nitrate-free generator eluates in (99m)Tc-sestamibi preparations to improve the
      product quality and prevent unnecessary exposure of the patient to radiation.

PMID- 22872665
TI  - Modeling of caterpillar crawl using novel tensegrity structures.
AB  - Caterpillars are soft-bodied animals. They have a relatively simple nervous
      system, and yet are capable of exhibiting complex movement. This paper presents a
      2D caterpillar simulation which mimics caterpillar locomotion using Assur
      tensegrity structures. Tensegrity structures are structures composed of a set of
      elements always under compression and a set of elements always under tension.
      Assur tensegrities are a novel sub-group of tensegrity structures. In the model,
      each caterpillar segment is represented by a 2D Assur tensegrity structure called
      a triad. The mechanical structure and the control scheme of the model are
      inspired by the biological caterpillar. The unique engineering properties of
      Assur tensegrity structures, together with the suggested control scheme, provide
      the model with a controllable degree of softness-each segment can be either soft
      or rigid. The model exhibits several characteristics which are analogous to those
      of the biological caterpillar. One such characteristic is that the internal
      pressure of the caterpillar is not a function of its size. During growth, body
      mass is increased 10 000-fold, while internal pressure remains constant. In the
      same way, the model is able to maintain near constant internal forces regardless
      of size. The research also suggests that caterpillars do not invest considerably
      more energy while crawling than while resting.

PMID- 22872666
TI  - Numerical study of axonal outgrowth in grooved nerve conduits.
AB  - Nerve conduits with grooved inner texture, working as a topographical guidance
      cue, have been experimentally proved to play a significant role in axonal
      alignment. How grooved conduits guide axonal outgrowth is of particular interest
      for studying nerve regeneration. A viscoelastic model of axonal outgrowth in a
      conduit with a defined grooved geometry characterized by its width in the
      circumferential direction and its height in the radial direction is developed in
      this work. In this model, the axon is considered as an elastic beam and the
      axonal deformation and motion, including stretching, bending and torsion, are
      described using a Cosserat rod theory. The friction between axon and substrate is
      also considered in this model as well as the tip outgrowth. It is found that the
      directional outgrowth of the axon can be significantly improved by the grooved
      texture: when the groove width decreases or the groove height increases, the
      axonal elongation in the longitudinal direction of the conduit can be increased,
      which is in good agreement with experimental observations. This work is the first
      numerical model to study the effect of the substrate geometry on axonal
      outgrowth.

PMID- 22872667
TI  - Neurological picture. Multiple cerebral air emboli during upper gastrointestinal
      endoscopy.

PMID- 22872668
TI  - Sparse representation-based classification scheme for motor imagery-based brain
      computer interface systems.
AB  - Motor imagery (MI)-based brain-computer interface systems (BCIs) normally use a
      powerful spatial filtering and classification method to maximize their
      performance. The common spatial pattern (CSP) algorithm is a widely used spatial
      filtering method for MI-based BCIs. In this work, we propose a new sparse
      representation-based classification (SRC) scheme for MI-based BCI applications.
      Sensorimotor rhythms are extracted from electroencephalograms and used for
      classification. The proposed SRC method utilizes the frequency band power and CSP
      algorithm to extract features for classification. We analyzed the performance of
      the new method using experimental datasets. The results showed that the SRC
      scheme provides highly accurate classification results, which were better than
      those obtained using the well-known linear discriminant analysis classification
      method. The enhancement of the proposed method in terms of the classification
      accuracy was verified using cross-validation and a statistical paired t-test (p <
      0.001).

PMID- 22872669
TI  - Atopic keratoconjunctivitis: present day diagnosis.

PMID- 22872670
TI  - Myopic shift of foldable acrylic intraocular lenses after sulcus fixation.
AB  - AIMS: The aim of this retrospective study was to identify factors affecting
      myopic shift from predicted values of refraction after sulcus fixation of
      foldable acrylic intraocular lenses (IOLs). METHODS: A total of 91 eyes from 91
      consecutive patients, each of whom underwent primary implantation of sulcus
      fixated foldable acrylic IOLs, were assessed. AcrySof MA60BM and Sensar AR40e
      multi-piece IOLs, and AcrySof SA60AT and BioVue single-piece IOLs were implanted.
      The type of IOL and axial length (AL) were analysed to identify differences in
      the spherical equivalent between the predicted refraction values obtained using
      the SRK/T formula and the manifested refraction values. RESULTS: The mean myopic
      shift from the predicted refraction calculated using the SRK/T formula was -1.04
      dioptres (D) +/-0.85 SD with sulcus fixation of the foldable acrylic IOLs. The
      type of IOL (multi-piece vs single-piece) did not affect the degree of myopic
      shift (p=0.100, independent t-test). However, as the AL increased, the myopic
      shift decreased (p=0.033, r=0.223, Pearson's correlation). CONCLUSION: The myopic
      shift from the predicted refraction differed following sulcus fixation of
      foldable acrylic IOLs based on the AL, and therefore surgeons should take the AL
      into account when they determine the IOL power for sulcus fixation procedures.

PMID- 22872671
TI  - Google-based search of common blinding diseases: a reflection of public concerns.

PMID- 22872672
TI  - Choroidal nevi in adult Indians: The Central India Eye and Medical Study.

PMID- 22872673
TI  - Treating early choroidal neovascularisation with pegaptanib sodium in patients
      with neovascular age-related macular degeneration: findings of the PERSPECTIVES
      study.

PMID- 22872674
TI  - Enophthalmos following orbital trauma: a diagnostic catch.

PMID- 22872675
TI  - A helminth cathelicidin-like protein suppresses antigen processing and
      presentation in macrophages via inhibition of lysosomal vATPase.
AB  - We previously reported the identification of a novel family of immunomodulatory
      proteins, termed helminth defense molecules (HDMs), that are secreted by
      medically important trematode parasites. Since HDMs share biochemical,
      structural, and functional characteristics with mammalian cathelicidin-like host
      defense peptides (HDPs), we proposed that HDMs modulate the immune response via
      molecular mimicry of host molecules. In the present study, we report the
      mechanism by which HDMs influence the function of macrophages. We show that the
      HDM secreted by Fasciola hepatica (FhHDM-1) binds to macrophage plasma membrane
      lipid rafts via selective interaction with phospholipids and/or cholesterol
      before being internalized by endocytosis. Following internalization, FhHDM-1 is
      rapidly processed by lysosomal cathepsin L to release a short C-terminal peptide
      (containing a conserved amphipathic helix that is a key to HDM function), which
      then prevents the acidification of the endolysosomal compartments by inhibiting
      vacuolar ATPase activity. The resulting endolysosomal alkalization impedes
      macrophage antigen processing and prevents the transport of peptides to the cell
      surface in conjunction with MHC class II for presentation to CD4(+) T cells.
      Thus, we have elucidated a novel mechanism by which helminth pathogens alter
      innate immune cell function to assist their survival in the host.

PMID- 22872676
TI  - Interstrain differences in the severity of liver injury induced by a choline- and
      folate-deficient diet in mice are associated with dysregulation of genes involved
      in lipid metabolism.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading
      cause of chronic liver disease in the United States and developed countries. In
      humans, genetic factors greatly influence individual susceptibility to NAFLD. The
      goals of this study were to compare the magnitude of interindividual differences
      in the severity of liver injury induced by methyl-donor deficiency among
      individual inbred strains of mice and to investigate the underlying mechanisms
      associated with the variability. Feeding mice a choline- and folate-deficient
      diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver
      injury varied among the strains, with the order of sensitivity being A/J ~
      C57BL/6J ~ C3H/HeJ < 129S1/SvImJ ~ CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain
      variability in severity of NAFLD liver damage was associated with dysregulation
      of genes involved in lipid metabolism, primarily with a down-regulation of the
      peroxisome proliferator receptor alpha (PPARalpha)-regulated lipid catabolic
      pathway genes. Markers of oxidative stress and oxidative stress-induced DNA
      damage were also elevated in the livers but were not correlated with severity of
      liver damage. These findings suggest that the PPARalpha-regulated metabolism
      network is one of the key mechanisms determining interstrain susceptibility and
      severity of NAFLD in mice.

PMID- 22872677
TI  - KAP1 regulates gene networks controlling T-cell development and responsiveness.
AB  - Chromatin remodeling at specific genomic loci controls lymphoid differentiation.
      Here, we investigated the role played in this process by Kruppel-associated box
      (KRAB)-associated protein 1 (KAP1), the universal cofactor of KRAB-zinc finger
      proteins (ZFPs), a tetrapod-restricted family of transcriptional repressors. T
      cell-specific Kap1-deleted mice displayed a significant expansion of immature
      thymocytes, imbalances in CD4(+)/CD8(+) cell ratios, and altered responses to TCR
      and TGFbeta stimulation when compared to littermate KAP1 control mice.
      Transcriptome and chromatin studies revealed that KAP1 binds T-cell-specific cis
      acting regulatory elements marked by the H3K9me3 repressive mark and enriched in
      Ikaros/NuRD complexes. Also, KAP1 directly controls the expression of several
      genes involved in TCR and cytokine signaling. Among these, regulation of FoxO1
      seems to play a major role in this system. Likely responsible for tethering KAP1
      to at least part of its genomic targets, a small number of KRAB-ZFPs are
      selectively expressed in T-lymphoid cells. These results reveal the so far
      unsuspected yet important role of KAP1-mediated epigenetic regulation in T
      lymphocyte differentiation and activation.

PMID- 22872678
TI  - Translational attenuation differentially alters the fate of disease-associated
      fibulin proteins.
AB  - Mutations in fibulin proteins that cause cellular secretion deficiencies are
      linked to a variety of diseases, ranging from retinopathies to cutis laxa (CL).
      One secretion-deficient fibulin mutant, R345W fibulin-3, causes the macular
      dystrophy malattia leventinese by increased endoplasmic reticulum retention
      and/or extracellular misfolding. Herein, we report that small-molecule activation
      of the PERK arm of the unfolded protein response partially rescues R345W
      secretion deficiencies through translational attenuation mediated by eIF2alpha
      phosphorylation. Enhanced mutant fibulin-3 secretion can also be achieved by
      activation of a PERK-independent eIF2alpha kinase through arsenite treatment and
      is independent of activating transcription factor 4 signaling and protein
      translation. However, this translational attenuation strategy was unsuccessful
      for enhancing the secretion deficiencies of fibulin-5 mutants associated with age
      related macular degeneration or CL. While lowered growth temperature enhanced the
      secretion of mutants associated with CL (C217R and S227P), these effects were not
      mediated through translational attenuation. In stark contrast to the situation
      with fibulin-3, protein translation was required for efficient wild-type and
      mutant fibulin-5 secretion. These data suggest that alteration of specific
      cellular signaling pathways and proteostasis network components can
      differentially influence fibulin fate, a hypothesis that could be exploited as a
      therapy for fibulin-related diseases.

PMID- 22872679
TI  - Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and
      enfuvirtide-resistant HIV-1.
AB  - Understanding the structural organization of lipids in the cell and viral
      membranes is essential for elucidating mechanisms of viral fusion that lead to
      entry of enveloped viruses into their host cells. The HIV lipidome shows a
      remarkable enrichment in dihydrosphingomyelin, an unusual sphingolipid formed by
      a dihydrosphingosine backbone. Here we investigated the ability of
      dihydrosphingosine to incorporate into the site of membrane fusion mediated by
      the HIV envelope (Env) protein. Dihydrosphingosine as well as cholesterol, fatty
      acid, and tocopherol was conjugated to highly conserved, short HIV-1 Env-derived
      peptides with no antiviral activity otherwise. We showed that dihydrosphingosine
      exclusively endowed nanomolar antiviral activity to the peptides (IC(50) as low
      as 120 nM) in HIV-1 infection on TZM-bl cells and on Jurkat T cells, as well as
      in the cell-cell fusion assay. These sphingopeptides were active against
      enfuvirtide-resistant and wild-type CXCR4 and CCR5 tropic HIV strains. The anti
      HIV activity was determined by both the peptides and their dihydrosphingosine
      conjugate. Moreover, their mode of action involved accumulation in the cells and
      viruses and binding to membranes enriched in sphingomyelin and cholesterol. The
      data suggest that sphingopeptides are recruited to the HIV membrane fusion site
      and provide a general concept in developing inhibitors of sphingolipid-mediated
      biological systems.

PMID- 22872680
TI  - Evaluation of systemic markers of inflammation in atomic-bomb survivors with
      special reference to radiation and age effects.
AB  - Past exposure to atomic bomb (A-bomb) radiation has exerted various long-lasting
      deleterious effects on the health of survivors. Some of these effects are seen
      even after >60 yr. In this study, we evaluated the subclinical inflammatory
      status of 442 A-bomb survivors, in terms of 8 inflammation-related cytokines or
      markers, comprised of plasma levels of reactive oxygen species (ROS), interleukin
      (IL)-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), IL-4,
      IL-10, and immunoglobulins, and erythrocyte sedimentation rate (ESR). The effects
      of past radiation exposure and natural aging on these markers were individually
      assessed and compared. Next, to assess the biologically significant relationship
      between inflammation and radiation exposure or aging, which was masked by the
      interrelationship of those cytokines/markers, we used multivariate statistical
      analyses and evaluated the systemic markers of inflammation as scores being
      calculated by linear combinations of selected cytokines and markers. Our results
      indicate that a linear combination of ROS, IL-6, CRP, and ESR generated a score
      that was the most indicative of inflammation and revealed clear dependences on
      radiation dose and aging that were found to be statistically significant. The
      results suggest that collectively, radiation exposure, in conjunction with
      natural aging, may enhance the persistent inflammatory status of A-bomb
      survivors.

PMID- 22872681
TI  - Artefacts in measuring joint moments may lead to incorrect clinical conclusions:
      the nexus between science (biomechanics) and sports injury prevention!

PMID- 22872682
TI  - An active pregnancy for fetal well-being? The value of active living for most
      women and their babies.

PMID- 22872683
TI  - Statistical modelling for recurrent events: an application to sports injuries.
AB  - BACKGROUND: Injuries are often recurrent, with subsequent injuries influenced by
      previous occurrences and hence correlation between events needs to be taken into
      account when analysing such data. OBJECTIVE: This paper compares five different
      survival models (Cox proportional hazards (CoxPH) model and the following
      generalisations to recurrent event data: Andersen-Gill (A-G), frailty, Wei-Lin
      Weissfeld total time (WLW-TT) marginal, Prentice-Williams-Peterson gap time (PWP
      GT) conditional models) for the analysis of recurrent injury data. METHODS:
      Empirical evaluation and comparison of different models were performed using
      model selection criteria and goodness-of-fit statistics. Simulation studies
      assessed the size and power of each model fit. RESULTS: The modelling approach is
      demonstrated through direct application to Australian National Rugby League
      recurrent injury data collected over the 2008 playing season. Of the 35 players
      analysed, 14 (40%) players had more than 1 injury and 47 contact injuries were
      sustained over 29 matches. The CoxPH model provided the poorest fit to the
      recurrent sports injury data. The fit was improved with the A-G and frailty
      models, compared to WLW-TT and PWP-GT models. CONCLUSIONS: Despite little
      difference in model fit between the A-G and frailty models, in the interest of
      fewer statistical assumptions it is recommended that, where relevant, future
      studies involving modelling of recurrent sports injury data use the frailty model
      in preference to the CoxPH model or its other generalisations. The paper provides
      a rationale for future statistical modelling approaches for recurrent sports
      injury.

PMID- 22872684
TI  - Perceived key injury risk factors in World Cup alpine ski racing--an explorative
      qualitative study with expert stakeholders.
AB  - BACKGROUND: There is limited knowledge about key injury risk factors in alpine
      ski racing, particularly for World Cup (WC) athletes. OBJECTIVE: This study was
      undertaken to compile and explore perceived intrinsic and extrinsic risk factors
      for severe injuries in WC alpine ski racing. METHODS: Qualitative study.
      Interviews were conducted with 61 expert stakeholders of the WC ski racing
      community. Experts' statements were collected, paraphrased and loaded into a
      database with inductively derived risk factor categories (Risk Factor Analysis).
      At the end of the interviews, experts were asked to name those risk factors they
      believed to have a high potential impact on injury risk and to rank them
      according to their priority of impact (Risk Factor Rating). RESULTS: In total, 32
      perceived risk factors categories were derived from the interviews within the
      basic categories Athlete, Course, Equipment and Snow. Regarding their perceived
      impact on injury risk, the experts' top five categories were: system ski,
      binding, plate and boot; changing snow conditions; physical aspects of the
      athletes; speed and course setting aspects and speed in general. CONCLUSIONS:
      Severe injuries in WC alpine ski racing can have various causes. This study
      compiled a list of perceived intrinsic and extrinsic risk factors and explored
      those factors with the highest believed impact on injury risk. Hence, by using
      more detailed hypotheses derived from this explorative study, further studies
      should verify the plausibility of these factors as true risk factors for severe
      injuries in WC alpine ski racing.

PMID- 22872686
TI  - Glucocorticoid replacement and mortality in patients with nonfunctioning
      pituitary adenoma.
AB  - CONTEXT: Current treatment guidelines generally suggest using lower and weight
      adjusted glucocorticoid replacement doses in patients with insufficiency of the
      hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with
      acromegaly revealed a positive association between glucocorticoid dose and
      mortality, no comparable results exist in patients with nonfunctioning pituitary
      adenomas (NFPA). OBJECTIVE: Our objective was to assess whether higher
      glucocorticoid replacement doses are associated with increased mortality in
      patients with NFPA and HPA axis insufficiency. DESIGN, PARTICIPANTS, AND
      INTERVENTION: We included 105 patients receiving glucocorticoid replacement after
      pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients
      were grouped according weight-adapted and absolute hydrocortisone (HC)
      replacement doses. Mortality was assessed using Kaplan-Meier methodology as well
      as multivariable Cox regression models. SETTING: This was a retrospective
      analysis conducted at a tertiary referral center. MAIN OUTCOME: We evaluated
      overall mortality based on HC replacement doses. RESULTS: Average age at
      inclusion was 58.9+/-14.8 yr, and mean follow-up was 12.7+/-9.4 yr. The groups
      did not differ according to age, follow-up time, pattern of hypopituitarism, and
      comorbidities. Kaplan-Meier survival probabilities differed significantly when
      comparing individuals with differing weight-adjusted HC dose (P=0.001) as well as
      absolute HC dose (5-19, 20-29, and >=30 mg, P=0.009). Hazard ratios for mortality
      increased from 1 (0.05-0.24 mg/kg) to 2.62 (0.25-0.34 mg/kg) to 4.56 (>=0.35
      mg/kg, P for trend=0.006) and from 1 (5-19 mg) to 2.03 (20-29 mg) to 4 (>=30 mg,
      P for trend=0.029), respectively. CONCLUSION: Higher glucocorticoid replacement
      doses are associated with increased overall mortality in patients with NFPA and
      insufficiency of HPA axis. This further substantiates the importance of a
      balanced and adjusted glucocorticoid replacement therapy in these patients.

PMID- 22872685
TI  - Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2,
      and pegylated interferon-alpha 2a specifically targets JAK2V617F-positive
      polycythemia vera cells.
AB  - Interferon (IFN-alpha) is effective therapy for polycythemia vera (PV) patients,
      but it is frequently interrupted because of adverse events. To permit the long
      term use of IFN, we propose combining low doses of IFN with Nutlin-3, an
      antagonist of MDM2, which is also capable of promoting PV CD34(+) cell apoptosis.
      Combination treatment with subtherapeutic doses of Peg IFN-alpha 2a and Nutlin-3
      inhibited PV CD34(+) cell proliferation by 50% while inhibiting normal CD34(+)
      cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-alpha 2a inhibited
      PV colony formation by 55%-90% while inhibiting normal colony formation by 22%
      30%. The combination of these agents also decreased the proportion of JAK2V617F
      positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with
      low doses of Peg IFN-alpha 2a combined with Nutlin-3 increased phospho-p53 and
      p21 protein levels in PV CD34(+) cells and increased the degree of apoptosis.
      These 2 reagents affect the tumor suppressor p53 through different pathways with
      Peg IFN-alpha 2a activating p38 MAP kinase and STAT1, leading to increased p53
      transcription, whereas Nutlin-3 prevents the degradation of p53. These data
      suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN
      alpha 2a can target PV hematopoietic progenitor cells, eliminating the numbers of
      malignant hematopoietic progenitor cells.

PMID- 22872687
TI  - Role of 11betaHSD type 2 enzyme activity in essential hypertension and children
      with chronic kidney disease (CKD).
AB  - BACKGROUND: The mineralocorticoid receptor is protected from excess of
      glucocorticoids by conversion of active cortisol to inactive cortisone by enzyme
      11beta-hydroxysteroid dehydrogenase type 2 present in the kidney. The metabolites
      of cortisol and cortisone are excreted in the urine as tetrahydrocortisol
      (5alphaTHF+5betaTHF) and tetrahydrocortisone (THE), respectively. HYPOTHESIS:
      Patients with chronic kidney disease (CKD) and essential hypertension have a
      functional defect in their ability to convert cortisol to cortisone, thus leading
      to the activation of mineralocorticoid receptor. OBJECTIVE: The objective of the
      investigation was to study the ratio of urinary steroids (5alphaTHF+5betaTHF) to
      THE in patients with CKD, postrenal transplant, and essential hypertension and to
      compare the ratio with controls. DESIGN/METHODS: We enrolled 44 patients (17 with
      CKD, eight postrenal transplant, 19 with essential hypertension) and 12 controls.
      We measured spot urinary 5alpha-THF, 5beta-THF, THE, free active cortisol and
      inactive cortisone by gas chromatography/mass spectrometry. We collected data on
      age, sex, cause of kidney disease, height, weight, body mass index, blood
      pressure, serum electrolytes, aldosterone, and plasma renin activity. Blood
      pressure percentiles and z-scores were calculated. The glomerular filtration rate
      was calculated using the modified Schwartz formula. RESULTS: The ratios of
      5alphaTHF+5betaTHF to THE were significantly higher in patients with CKD [mean+/
      sd score (SDS)=1.31+/-1.07] as compared with essential hypertension (mean+/
      SDS=0.59+/-0.23; P=0.02) and controls (mean+/-SDS=0.52+/-0.25; P=0.01). In the
      postrenal transplant group, the ratio was not significantly different (mean+/
      SDS=0.71+/-0.55). The urinary free cortisol to free cortisone ratios were
      significantly higher in the hypertension and CKD groups as compared with the
      controls. The 5alphaTHF+5betaTHF to THE ratio negatively correlated with the
      glomerular filtration rate and positively correlated with systolic and diastolic
      blood pressure z-scores. The correlation of the blood pressure z-scores with
      ratios was stronger in the CKD group than the essential hypertension and
      posttransplant groups. CONCLUSIONS: We have elucidated a functional deficiency of
      11beta-hydroxysteroid dehydrogenase type 2 in children with CKD and a subset of
      essential hypertension. Urinary 5alpha-THF, 5beta-THF, and THE analysis by gas
      chromatography/mass spectrometry should be a part of routine work-up of CKD and
      hypertensive patients.

PMID- 22872688
TI  - Oxytocin secretion is associated with severity of disordered eating
      psychopathology and insular cortex hypoactivation in anorexia nervosa.
AB  - CONTEXT: Animal data suggest that oxytocin is a satiety hormone. We have
      demonstrated that anorexia nervosa (anorexia), a disorder characterized by food
      restriction, low weight, and hypoleptinemia, is associated with decreased
      nocturnal oxytocin secretion. We have also reported functional magnetic resonance
      imaging (fMRI) hypoactivation in anorexia in brain regions involved in food
      motivation. The relationships between oxytocin, food-motivation neurocircuitry,
      and disordered eating psychopathology have not been investigated in humans.
      OBJECTIVE: The objective of the study was to determine whether the oxytocin
      response to feeding in anorexia differs from healthy women and to establish the
      relationship between oxytocin secretion and disordered eating psychopathology and
      food-motivation neurocircuitry. DESIGN: This was a cross-sectional study.
      SETTING: The study was conducted at a clinical research center. PARTICIPANTS:
      Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia
      (ANWR), and 13 healthy controls (HC). MEASURES: Peripheral oxytocin and leptin
      levels were measured fasting and 30, 60, and 120 min after a standardized mixed
      meal. The Eating Disorder Examination-Questionnaire was used to assess disordered
      eating psychopathology. fMRI was performed during visual processing of food and
      nonfood stimuli to measure brain activation before and after the meal. RESULTS:
      Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in
      ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area
      under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR.
      Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR.
      Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN.
      Oxytocin AUC was associated with the severity of disordered eating
      psychopathology in AN and ANWR, independent of leptin secretion, and was
      associated with between-group variance in fMRI activation in food motivation
      brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal
      cortex, and insula. CONCLUSIONS: Oxytocin may be involved in the pathophysiology
      of anorexia.

PMID- 22872689
TI  - Effect of tight glucose control with insulin on the thyroid axis of critically
      ill children and its relation with outcome.
AB  - CONTEXT: Tight glucose control (TGC) to normal-for-age fasting blood glucose
      levels reduced morbidity and mortality in surgical adult and pediatric intensive
      care unit (ICU) patients. In adults, TGC did not affect the illness-induced
      alterations in thyroid hormones. With better feeding in children than in adult
      patients, we hypothesized that TGC in pediatric ICU patients reactivates the
      thyroid axis. OBJECTIVE: The aim of this study was to assess the impact of TGC on
      the thyroid axis in pediatric ICU patients and to investigate how these changes
      affect the TGC outcome benefit. DESIGN AND PATIENTS: We conducted a preplanned
      analysis of all patients not treated with thyroid hormone, dopamine, or
      corticosteroids who were included in a randomized controlled trial on TGC
      (n=700). MAIN OUTCOME MEASURES: Serum TSH, T4, T3, and rT3 were measured upon
      admission and on ICU day 3 or the last ICU day for patients discharged earlier.
      Changes from baseline were compared for the TGC and usual care groups. The impact
      on the outcome benefit of TGC was assessed with multivariable Cox proportional
      hazard analysis, correcting for baseline risk factors. RESULTS: TGC further
      lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were
      unaltered. With TGC, the likelihood of earlier live discharge from the ICU was
      19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010
      1.407; P=0.03). This benefit was statistically explained by the further reduction
      of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a
      lower likelihood for earlier live discharge (hazard ratio per unit increase,
      0.863; 95% confidence interval, 0.806-0.927; P<0.0001). CONCLUSIONS: TGC further
      accentuated the peripheral inactivation of thyroid hormone. This effect,
      mimicking a fasting response, statistically explained part of the clinical
      outcome benefit of TGC.

PMID- 22872690
TI  - Low circulating adropin concentrations with obesity and aging correlate with risk
      factors for metabolic disease and increase after gastric bypass surgery in
      humans.
AB  - CONTEXT: Mouse studies suggest that adropin, a peptide hormone, is required for
      metabolic homeostasis and prevention of obesity-associated insulin resistance.
      Whether obesity and insulin resistance are associated with low plasma adropin
      levels in humans is not known. OBJECTIVES: Our objective was to investigate the
      hypothesis that obesity and indicators of insulin resistance are associated with
      low adropin levels and determine whether weight loss regulates adropin levels.
      DESIGN AND PARTICIPANTS: Plasma was obtained from 85 female [age 21-67 yr, body
      mass index (BMI) 19.4-71.5 kg/m2] and 45 male (age 18-70 yr, BMI 19.1-62.6 kg/m2)
      volunteers for other clinical studies. The impact of Roux-en-Y gastric bypass was
      investigated in 19 obese females (BMI 37-65 kg/m2) using samples collected at
      baseline and 1-12 months after surgery. RESULTS: Adropin levels correlate
      negatively with BMI (r=-0.335, P<0.001) and age (r=-0.263, P=0.003). Age-adjusted
      adropin levels are higher in males [4.1 ng/ml; 95% confidence interval (CI)=3.6
      4.6 ng/ml] than females (3.0 ng/ml; 95% CI=2.6-3.4 ng/ml) (P=0.001). In all
      subjects, lower age-adjusted adropin levels were observed in overweight (3.3
      ng/ml; 95% CI=2.8-3.8 ng/ml, P=0.033) and obese (2.7 ng/ml; 95% CI=2.1-3.3 ng/ml,
      P=0.001) compared with healthy-weight subjects (4.1 ng/ml; 95% CI=3.6-4.5 ng/ml).
      This effect was gender specific (weight category*gender, P<0.001) and was
      observed in males only. Aging and diagnosis with two or more metabolic syndrome
      risk factors was associated with low adropin levels, irrespective of sex. Adropin
      concentrations increased after Roux-en-Y gastric bypass, peaking 3 months after
      surgery (P<0.01). CONCLUSIONS: Although males exhibit higher adropin levels that
      are reduced by obesity, aging and markers of insulin resistance are associated
      with low plasma adropin irrespective of sex.

PMID- 22872691
TI  - Increased cellular and circulating biomarkers of oxidative stress in nascent
      metabolic syndrome.
AB  - CONTEXT: Metabolic syndrome (MetS) confers a greater risk for both cardiovascular
      disease (CVD) and diabetes. Oxidative stress (OS) could contribute to this excess
      risk. However, there are few data examining both cellular and circulating
      biomarkers of OS in MetS uncomplicated by diabetes and CVD. OBJECTIVE: The aim of
      the study was to evaluate both cellular and circulating biomarkers of OS in MetS
      uncomplicated by diabetes or CVD. DESIGN AND SETTING: At an academic medical
      center, we compared MetS (n=43) vs. control subjects (n=33). Fasting blood was
      collected for monocyte isolation and assay of OS biomarkers. MAIN OUTCOME:
      Monocyte nicotinamide adenine dinucleotide phosphate oxidase activity (p22 phox
      and p47), superoxide anion release, oxidized-low-density lipoprotein (Ox-LDL),
      nitrotyrosine, and nuclear factor erythroid 2-related factor were measured.
      RESULTS: There was significantly increased release of superoxide from the
      monocytes (basal and after activation) of MetS compared with controls adjusted
      for body mass index. Body mass index-adjusted plasma levels of Ox-LDL and
      nitrotyrosine were significantly increased in MetS. There was a linear trend
      between biomarkers of oxidative stress and increasing number of features of MetS.
      Also, there was a significant increase in nicotinamide adenine dinucleotide
      phosphate oxidase membrane expression of p22 phox and p47 phox in MetS. The major
      cellular antioxidant defense, nuclear factor erythroid 2-related factor was
      significantly decreased. There were significant correlations between homeostasis
      model assessment insulin resistance index and both Ox-LDL and nitrotyrosine and
      superoxide and Ox-LDL. CONCLUSIONS: Collectively, nascent MetS is associated with
      increased OS as evidenced by both circulating and cellular biomarkers, and this
      could contribute to the risk for both diabetes and CVD.

PMID- 22872693
TI  - Raising the bar for market authorisation of new drugs.

PMID- 22872692
TI  - Functional magnetic resonance imaging analysis of food-related brain activity in
      patients with lipodystrophy undergoing leptin replacement therapy.
AB  - CONTEXT: Lipodystrophy is a disease characterized by a paucity of adipose tissue
      and low circulating concentrations of adipocyte-derived leptin. Leptin
      replacement therapy improves eating and metabolic disorders in patients with
      lipodystrophy. OBJECTIVE: The aim of the study was to clarify the pathogenic
      mechanism of eating disorders in lipodystrophic patients and the action mechanism
      of leptin on appetite regulation. SUBJECTS AND INTERVENTIONS: We investigated
      food-related neural activity using functional magnetic resonance imaging in
      lipodystrophic patients with or without leptin replacement therapy and in healthy
      controls. We also measured the subjective feelings of appetite. RESULTS: Although
      there was little difference in the enhancement of neural activity by food stimuli
      between patients and controls under fasting, postprandial suppression of neural
      activity was insufficient in many regions of interest including amygdala, insula,
      nucleus accumbens, caudate, putamen, and globus pallidus in patients when
      compared with controls. Leptin treatment effectively suppressed postprandial
      neural activity in many of these regions of interest, whereas it showed little
      effect under fasting in patients. Consistent with these results, postprandial
      formation of satiety feeling was insufficient in patients when compared with
      controls, which was effectively reinforced by leptin treatment. CONCLUSIONS: This
      study demonstrated the insufficiency of postprandial suppression of food-related
      neural activity and formation of satiety feeling in lipodystrophic patients,
      which was effectively restored by leptin. The findings in this study emphasize
      the important pathological role of leptin in eating disorders in lipodystrophy
      and provide a clue to understanding the action mechanism of leptin in human,
      which may lead to development of novel strategies for prevention and treatment of
      obesity.

PMID- 22872694
TI  - Pharmaceutical research and development: what do we get for all that money?

PMID- 22872696
TI  - Preventing falls in older people.

PMID- 22872695
TI  - Integration of balance and strength training into daily life activity to reduce
      rate of falls in older people (the LiFE study): randomised parallel trial.
AB  - OBJECTIVES: To determine whether a lifestyle integrated approach to balance and
      strength training is effective in reducing the rate of falls in older, high risk
      people living at home. DESIGN: Three arm, randomised parallel trial; assessments
      at baseline and after six and 12 months. Randomisation done by computer generated
      random blocks, stratified by sex and fall history and concealed by an independent
      secure website. SETTING: Residents in metropolitan Sydney, Australia.
      PARTICIPANTS: Participants aged 70 years or older who had two or more falls or
      one injurious fall in past 12 months, recruited from Veteran's Affairs databases
      and general practice databases. Exclusion criteria were moderate to severe
      cognitive problems, inability to ambulate independently, neurological conditions
      that severely influenced gait and mobility, resident in a nursing home or hostel,
      or any unstable or terminal illness that would affect ability to do exercises.
      INTERVENTIONS: Three home based interventions: Lifestyle integrated Functional
      Exercise (LiFE) approach (n=107; taught principles of balance and strength
      training and integrated selected activities into everyday routines), structured
      programme (n=105; exercises for balance and lower limb strength, done three times
      a week), sham control programme (n=105; gentle exercise). LiFE and structured
      groups received five sessions with two booster visits and two phone calls;
      controls received three home visits and six phone calls. Assessments made at
      baseline and after six and 12 months. MAIN OUTCOME MEASURES: Primary measure:
      rate of falls over 12 months, collected by self report. Secondary measures:
      static and dynamic balance; ankle, knee and hip strength; balance self efficacy;
      daily living activities; participation; habitual physical activity; quality of
      life; energy expenditure; body mass index; and fat free mass. RESULTS: After 12
      months' follow-up, we recorded 172, 193, and 224 falls in the LiFE, structured
      exercise, and control groups, respectively. The overall incidence of falls in the
      LiFE programme was 1.66 per person years, compared with 1.90 in the structured
      programme and 2.28 in the control group. We saw a significant reduction of 31% in
      the rate of falls for the LiFE programme compared with controls (incidence rate
      ratio 0.69 (95% confidence interval 0.48 to 0.99)); the corresponding difference
      between the structured group and controls was non-significant (0.81 (0.56 to
      1.17)). Static balance on an eight level hierarchy scale, ankle strength,
      function, and participation were significantly better in the LiFE group than in
      controls. LiFE and structured groups had a significant and moderate improvement
      in dynamic balance, compared with controls. CONCLUSIONS: The LiFE programme
      provides an alternative to traditional exercise to consider for fall prevention.
      Functional based exercise should be a focus for interventions to protect older,
      high risk people from falling and to improve and maintain functional capacity.
      TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry
      12606000025538.

PMID- 22872697
TI  - We should not let families stop organ donation from their dead relatives.

PMID- 22872698
TI  - Exosomes and microvesicles: extracellular vesicles for genetic information
      transfer and gene therapy.
AB  - Exosomes and microvesicles are extracellular nanovesicles released by most but
      not all cells. They are specifically equipped to mediate intercellular
      communication via the transfer of genetic information, including the transfer of
      both coding and non-coding RNAs, to recipient cells. As a result, both exosomes
      and microvesicles play a fundamental biological role in the regulation of normal
      physiological as well as aberrant pathological processes, via altered gene
      regulatory networks and/or via epigenetic programming. For example, microvesicle
      mediated genetic transfer can regulate the maintenance of stem cell plasticity
      and induce beneficial cell phenotype modulation. Alternatively, such vesicles
      play a role in tumor pathogenesis and the spread of neurodegenerative diseases
      via the transfer of specific microRNAs and pathogenic proteins. Given this
      natural property for genetic information transfer, the possibility of exploiting
      these vesicles for therapeutic purposes is now being investigated. Stem cell
      derived microvesicles appear to be naturally equipped to mediate tissue
      regeneration under certain conditions, while recent evidence suggests that
      exosomes might be harnessed for the targeted delivery of human genetic therapies
      via the introduction of exogenous genetic cargoes such as siRNA. Thus,
      extracellular vesicles are emerging as potent genetic information transfer agents
      underpinning a range of biological processes and with therapeutic potential.

PMID- 22872699
TI  - High-content RNAi screening identifies the Type 1 inositol triphosphate receptor
      as a modifier of TDP-43 localization and neurotoxicity.
AB  - Cytosolic aggregation of the nuclear RNA-binding protein (RBP) TDP-43 (43 kDa TAR
      DNA-binding domain protein) is a suspected direct or indirect cause of motor
      neuron deterioration in amyotrophic lateral sclerosis (ALS). In this study, we
      implemented a high-content, genome-wide RNAi screen to identify pathways
      controlling TDP-43 nucleocytoplasmic shuttling. We identified ~60 genes whose
      silencing increased the cytosolic localization of TDP-43, including nuclear pore
      complex components and regulators of G2/M cell cycle transition. In addition, we
      identified the type 1 inositol-1,4,5-trisphosphate (IP3) receptor (ITPR1), an IP3
      gated, endoplasmic reticulum (ER)-resident Ca(2+) channel, as a strong modulator
      of TDP-43 nucleocytoplasmic shuttling. Knockdown or chemical inhibition of ITPR1
      induced TDP-43 nuclear export in immortalized cells and primary neurons and
      strongly potentiated the recruitment of TDP-43 to Ubiquilin-positive
      autophagosomes, suggesting that diminished ITPR1 function leads to autophagosomal
      clearance of TDP-43. The functional significance of the TDP-43-ITPR1 genetic
      interaction was tested in Drosophila, where mutant alleles of ITPR1 were found to
      significantly extended lifespan and mobility of flies expressing TDP-43 under a
      motor neuron driver. These combined findings implicate IP3-gated Ca(2+) as a key
      regulator of TDP-43 nucleoplasmic shuttling and proteostasis and suggest
      pharmacologic inhibition of ITPR1 as a strategy to combat TDP-43-induced
      neurodegeneration in vivo.

PMID- 22872700
TI  - Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking
      and ATF6 activation.
AB  - Although genetic variations in several genes encoding for synaptic adhesion
      proteins have been found to be associated with autism spectrum disorders, one of
      the most consistently replicated genes has been CNTNAP2, encoding for contactin
      associated protein-like 2 (CASPR2), a multidomain transmembrane protein of the
      neurexin superfamily. Using immunofluorescence confocal microscopy and
      complementary biochemical techniques, we compared wild-type CASPR2 to 12 point
      mutations identified in individuals with autism. In contrast to the wild-type
      protein, localized to the cell surface, some of the mutants show altered cellular
      disposition. In particular, CASPR2-D1129H is largely retained in the endoplasmic
      reticulum (ER) in HEK-293 cells and in hippocampal neurons. BiP/Grp78, Calnexin
      and ERp57, key ER chaperones, appear to be responsible for retention of this
      mutant and activation of one signaling pathway of the unfolded protein response
      (UPR). The presence of this mutation also lowers expression and activates
      proteosomal degradation. A frame-shift mutation that causes a form of syndromic
      epilepsy (CASPR2-1253*), results in a secreted protein with seemingly normal
      folding and oligomerization. Taken together, these data indicate that CASPR2
      D1129H has severe trafficking abnormalities and CASPR2-1253* is a secreted
      soluble protein, suggesting that the structural or signaling functions of the
      membrane tethered form are lost. Our data support a complex genetic architecture
      in which multiple distinct risk factors interact with others to shape autism risk
      and presentation.

PMID- 22872701
TI  - Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C
      disease.
AB  - Niemann-Pick type C disease (NPC) is a childhood onset neurodegenerative disorder
      arising from lipid-trafficking defects caused by mutations in the NPC1 or NPC2
      gene. Marked accumulation of autophagosomes is a prominent feature of NPC cells,
      yet a detailed understanding of the disease-associated alterations in autophagy
      and their role in pathogenesis has been lacking. Prior studies have shown that
      lipid storage in NPC disease induces autophagy. Here, we additionally show that
      the clearance of autophagosomes in NPC1 deficiency is impaired due to inhibition
      of lysosomal protease activity by stored lipids. We also demonstrate that the
      autophagic pathway is a source of stored cholesterol in the NPC lysosome, thus
      creating a positive feedback loop wherein autophagy induction exacerbates the
      disease via increased lipid storage. Inhibition of autophagy reduces cholesterol
      storage and restores normal lysosomal proteolysis in NPC1-deficient cells,
      supporting a model in which activation of the autophagic pathway promotes disease
      pathogenesis.

PMID- 22872702
TI  - ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress
      in neurons.
AB  - Mutations in several genes, including Parkin, PTEN-induced kinase 1 (Pink1) and
      DJ-1, are associated with rare inherited forms of Parkinson's disease (PD).
      Despite recent attention on the function of these genes, the interplay between DJ
      1, Pink1 and Parkin in PD pathogenesis remains unclear. In particular, whether
      these genes regulate mitochondrial control pathways in neurons is highly
      controversial. Here we report that Pink1-dependent Parkin translocation does
      occur in mouse cortical neurons in response to a variety of mitochondrial
      damaging agents. This translocation only occurs in the absence of antioxidants in
      the neuronal culturing medium, implicating a key role of reactive oxygen species
      (ROS) in this response. Consistent with these observations, ROS blockers also
      prevent Parkin recruitment in mouse embryonic fibroblasts. Loss of DJ-1, a gene
      linked to ROS management, results in increased stress-induced Parkin recruitment
      and increased mitophagy. Expression of wild-type DJ-1, but not a cysteine-106
      mutant associated with defective ROS response, rescues this accelerated Parkin
      recruitment. Interestingly, DJ-1 levels increase at mitochondria following
      oxidative damage in both fibroblasts and neurons, and this process also depends
      on Parkin and possibly Pink1. These results not only highlight the presence of a
      Parkin/Pink1-mediated pathway of mitochondrial quality control (MQC) in neurons,
      they also delineate a complex reciprocal relationship between DJ-1 and the
      Pink1/Parkin pathway of MQC.

PMID- 22872703
TI  - Effects of environmentally relevant mixtures of persistent organic pollutants on
      the developmental neurobiology in rats.
AB  - We report the developmental neuropathology for rat pups at postnatal day (PND) 37
      and PND 77 and the molecular biomarkers for PND 35, 75, and 350 after perinatal
      exposure to a reconstituted mixture of persistent organochlorine pollutants
      (POPs) based on the blood profiles of people living in the Great Lake Basin. The
      developmental neuropathology included routine histopathology evaluation,
      quantification of cell proliferation and death in the subventricular zone, linear
      morphometric measurements, and transcriptional analysis. No histopathological,
      structural, or stereological changes were observed in animals treated with the
      POPs or Aroclor 1254, on PND 37 or PND 77. While no transcriptional changes were
      found in Arcolor-treated animals, significant transcriptional changes were
      observed on PND 350 in female offspring perinatally exposed to 0.13 mg/kg of the
      POP mixture. Markers of the cholinergic system including acetylcholinesterase and
      the muscarinic receptors (subtypes M1-M5) were downregulated 2- to 6-fold. In
      addition, structural genes including neurofilaments (NFLs) and microtubule
      associated protein (MAP-2) were downregulated at least 2-fold or greater. Our
      results support that in utero and lactational exposure to the chemical mixture of
      POPs lead to developmental changes in adult rat brains.

PMID- 22872704
TI  - The handling and sampling of radical prostatectomy specimens for reporting and
      research: the Oxford approach.
AB  - This article reviews previously described methods of fresh tissue sampling from
      radical prostatectomy specimens for research and describes a method used in
      Oxford which is simple, logical and cost effective. The method utilises a
      systematic zonal approach to tissue procurement in order to meet the increasing
      requirement for research samples with detailed morphological information such as
      zone of origin, tumour stage and Gleason grade. The described method involves
      punch biopsy sampling from a 4mm thick transverse slice cut 8mm superior to the
      apex. 9 biopsies are taken from each specimen in the following zonal
      distribution: Mid anterior, right lateral, right peripheral zone lateral, right
      peripheral zone mid, left peripheral zone mid, left peripheral zone lateral, left
      lateral, left transition zone and right transition zone. The method was validated
      by successfully sampling tumour in 7 out of 8 cases (88%). In 6 of the positive
      cases, tumour was present in more than 1 punch biopsy. The mean time from receipt
      of the specimen to completion of the biopsy freezing was 23.5 minutes. Tumour
      stage, zone and Gleason grade were determined for all positive biopsies. All
      cases were reported to RCPath guidelines with no compromising of margins. A
      logical systematic method of fresh tissue sampling from radical prostatectomy
      specimens is presented, which balances the need for accurate routine
      histopathological reporting with the requirement for increasingly complex
      research samples to be taken with attention to morphological details such as zone
      and stage.

PMID- 22872705
TI  - Sanger sequencing in routine KRAS testing: a review of 1720 cases from a
      pathologist's perspective.
AB  - BACKGROUND: Sanger sequencing (SS) of PCR products is still the most frequent
      method to test colorectal cancer for KRAS mutations in routine practice. METHODS:
      An audit of SS on 1720 routine cases was carried out, taking into account age,
      gender, specimen type (resection vs biopsies), tumour site (primary vs
      metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation
      type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT)
      patients correlations between SS findings and response rate (RR), progression
      free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: The
      tests were informative in 1691 cases (98.3%). Mutations were detected in 671
      cases (39.6%). No significant differences in mutation rates were observed with
      respect to age (p=0.2), gender (p=0.2), specimen type (p=0.3) and formalin
      fixation (p=0.08). Conversely, KRAS mutant rate was higher in metastatic tissue
      (50% vs 39%, p=0.02), in samples with over 30% of neoplastic cells (43.4% vs
      26.6%, p=0.02) and in tumours tested in stage IV (p=0.05). The RR of SS KRAS WT
      patients was 26% (one complete and 12 partial responses). The disease control
      rate (objective responses plus stable disease) was 56%. Median PFS was 4.4 months
      and median OS was 10.4 months. CONCLUSIONS: Pathological criteria that make SS a
      more robust method for KRAS testing and treatment response prediction are
      neoplastic cell abundance, metastatic tissue sample and stage IV primary tumour.

PMID- 22872706
TI  - Referral centre variation in requesting JAK2 V617F mutation analysis for the
      investigation of a myeloproliferative neoplasm.

PMID- 22872707
TI  - Complications of Bioglue postsurgery for aortic dissections and aortic valve
      replacement.
AB  - AIMS: Bioglue is an adhesive used during cardiovascular surgery to improve
      hemostasis perioperatively and to strengthen and reinforce vascular anastomoses.
      It has also been used to 'seal' the false lumen in patients presenting with acute
      aortic dissections. Herein, we examine the complications of Bioglue, which may
      lead to redo sternotomy in selected patients. METHODS: A review of pathology
      records at our institution from 2002 to 2010 found 4 cases of excised aortic
      tissue and/or aortic valves with previous Bioglue use at initial operation.
      Excised tissues and valves were examined, looking for the presence of Bioglue,
      inflammatory cells (acute, chronic, macrophage and giant cells) and micro
      organisms. Patient demographics were also reviewed and recorded. RESULTS: We
      identified four cases of Bioglue use found at redo surgery, after the formation
      of pseudoaneurysm (n=3) and aortic stenosis (n=1). Mean interval to redo surgery
      was 2.28 + 0.32 years (range 2-2.6 years). Pseudoaneurysm formation was thought
      to be caused by an inflammatory reaction to the Bioglue itself in two cases,
      while one case found no such reaction. One patient with previous aortic valve
      replacement had large annular abscesses filled with necrotic debris surrounding
      the prosthesis and pannus found on the sewing cuff, comprised of Bioglue itself.
      CONCLUSIONS: The mechanisms leading to these complications include mechanical
      strain, inflammation and tissue necrosis. The judicious use of Bioglue when
      clinically indicated, and close follow-up of these patients with serial imaging,
      remain an integral part of avoiding future complications.

PMID- 22872708
TI  - Expect respect support groups: preliminary evaluation of a dating violence
      prevention program for at-risk youth.
AB  - Expect Respect support groups, a selective prevention strategy, are designed to
      prevent and reduce dating violence among at-risk middle and high school students.
      This preliminary, uncontrolled evaluation examined changes in healthy
      relationship skills and emotionally and physically abusive behaviors in
      participants' peer and dating relationships. Self-reports (N = 144) showed
      significant increases in healthy relationship skills from baseline to program
      completion, whereas levels of victimization and perpetration remained unchanged.
      A subgroup of students who reported baseline levels of victimization and
      perpetration with means at least one standard deviation above the group mean
      reported significantly less victimization and perpetration at program completion.

PMID- 22872709
TI  - Drug safety: reporting systems for the general public.

PMID- 22872711
TI  - Diagnosis and management of cellulitis.

PMID- 22872712
TI  - Heartfile: using technology to get healthcare funding to poor patients in
      Pakistan.

PMID- 22872710
TI  - Assessing the risk of venous thromboembolic events in women taking progestin-only
      contraception: a meta-analysis.
AB  - OBJECTIVES: To evaluate the risk of venous thromboembolic events associated with
      the use of progestin-only contraception and whether that risk differs with the
      mode of drug delivery (oral, intrauterine, or depot injection). DESIGN:
      Systematic review and meta-analysis of randomised controlled trials and
      observational studies. DATA SOURCES: Pubmed, Embase, Cochrane Library, and
      reference lists of relevant reviews. STUDY SELECTION: Randomised controlled
      trials and case-control, cohort, and cross sectional studies with venous
      thromboembolic outcome for progestin-only contraception reported relative to a
      non-hormone comparator group. DATA EXTRACTION: Data were extracted by two
      independent investigators, and consensus for inclusion was reached after
      assessment by additional investigators. RESULTS: Among the 2022 unique references
      identified by all searches, eight observational studies fulfilled inclusion
      criteria. A total of 147 women across all studies were diagnosed with a venous
      thromboembolic event while taking progestin-only contraception, and the summary
      measure for the adjusted relative risk of a venous thromboembolic episode for
      users versus non-users of a progestin-only contraceptive was, based on the random
      effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was
      no association between venous thromboembolic risk and progestin-only pills
      (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61
      (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of
      an injectable progestin versus non-users was 2.67 (1.29 to 5.53). CONCLUSIONS:
      Published data assessing the risk of venous thromboembolism in women prescribed
      progestin-only contraception are limited. In this meta-analysis of eight
      observational studies, the use of progestin-only contraception was not associated
      with an increased risk of venous thromboembolism compared with non-users of
      hormonal contraception. The potential association between injectable progestins
      and thrombosis requires further study.

PMID- 22872713
TI  - US health insurance firms issue $1.1bn in rebates to policy holders.

PMID- 22872714
TI  - Prime minister uses London Olympics to highlight challenge of global hunger.

PMID- 22872715
TI  - German government considers ending funding of marketing courses for doctors.

PMID- 22872716
TI  - Industry spending on continuing medical education in US falls further.

PMID- 22872717
TI  - Further care home scandals like Winterbourne are likely without action, warn
      campaigners.

PMID- 22872718
TI  - 'A Leg to Stand On' by Oliver Sacks: a unique autobiographical account of
      functional paralysis.
AB  - Oliver Sacks, the well known neurologist and writer, published his fourth book,
      'A Leg to Stand On', in 1984 following an earlier essay 'The Leg' in 1982. The
      book described his recovery after a fall in a remote region of Norway in which he
      injured his leg. Following surgery to reattach his quadriceps muscle, he
      experienced an emotional period in which his leg no longer felt a part of his
      body, and he struggled to regain his ability to walk. Sacks attributed the
      experience to a neurologically determined disorder of body-image and bodyego
      induced by peripheral injury. In the first edition of his book Sacks explicitly
      rejected the diagnosis of 'hysterical paralysis' as it was then understood,
      although he approached this diagnosis more closely in subsequent revisions. In
      this article we propose that, in the light of better understanding of functional
      neurological symptoms, Sacks' experiences deserve to be reappraised as a unique
      insight in to a genuinely experienced functional/psychogenic leg paralysis
      following injury.

PMID- 22872719
TI  - The central effects of peripheral injury.

PMID- 22872720
TI  - Functional disorders, Cartesian dualism and stigma: where does the dualism really
      lie?

PMID- 22872721
TI  - Covert checks by standardised patients of general practitioners' delivery of new
      periodic health examinations: clustered cross-sectional study from a consumer
      organisation.
AB  - OBJECTIVE: To assess if data collected by a consumer organisation are valid for a
      health service research study on physicians' performance in preventive care. To
      report first results of the analysis of physicians performance like consultation
      time and guideline adherence in history taking. DESIGN: Secondary data analysis
      of a clustered cross-sectional direct observation survey. SETTING: General
      practitioners (GPs) in Vienna, Austria, visited unannounced by mystery shoppers
      (incognito standardised patients (ISPs)). PARTICIPANTS: 21 randomly selected GPs
      were visited by two different ISPs each. 40 observation protocols were realised.
      MAIN OUTCOME MEASURES: Robustness of sampling and data collection by the consumer
      organisation. GPs consultation and waiting times, guideline adherence in history
      taking. RESULTS: The double stratified random sampling method was robust and
      representative for the private and contracted GPs mix of Vienna. The clinical
      scenarios presented by the ISPs were valid and believable, and no GP realised the
      ISPs were not genuine patients. The average consultation time was 46 min (95% CI
      37 to 54 min). Waiting times differed more than consultation times between
      private and contracted GPs. No differences between private and contracted GPs in
      terms of adherence to the evidence-based guidelines regarding history taking
      including questions regarding alcohol use were found. According to the analysis,
      20% of the GPs took a perfect history (95% CI 9% to 39%). CONCLUSIONS: The
      analysis of secondary data collected by a consumer organisation was a valid
      method for drawing conclusions about GPs preventive practice. Initial results,
      like consultation times longer than anticipated, and the moderate quality of
      history taking encourage continuing the analysis on available clinical data.

PMID- 22872722
TI  - Relation of sleep quality and sleep duration to type 2 diabetes: a population
      based cross-sectional survey.
AB  - OBJECTIVES: To investigate the association between self-reported sleep duration,
      sleep quality and the prevalence of diabetes in a contemporary sample of Chinese
      adults. DESIGN: Cross-sectional survey. SETTING: Community-based investigation in
      Xuzhou, China. PARTICIPANTS: 16 893 Chinese men and women aged 18-75 who
      fulfilled the inclusion and exclusion criteria were enrolled. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Self-reported quality and duration of sleep were
      obtained by questionnaire, and type 2 diabetes was assessed by fasting blood
      glucose. Sleep quality was categorised as good, common or poor. Sleep duration
      was measured by average hours of sleep per night, with categories of <=6 h, 6-8 h
      and >=8 h. A logistic regression model was used to evaluate the association
      between sleep duration or sleep quality and diabetes. RESULTS: Both poor quality
      of sleep and short sleep duration (<=6 h) were associated with increased
      prevalence of diabetes, with higher rates in relatively healthy Chinese people.
      Compared with the group with good quality of sleep and 6-8 h sleep duration,
      diabetes was the most prevalent in individuals with poor sleep quality and <=6 h
      sleep duration (OR 1.41, 95% CI 1.07 to 1.85) and in those with poor sleep
      quality who slept >=8 h (OR 1.39, 95% CI 0.85 to 2.26), even after adjustment for
      a large number of further possible factors. CONCLUSIONS: The results suggest that
      sleep of poor quality and short duration is associated with diabetes.

PMID- 22872723
TI  - Magnesium: the 'earth cure' of AKI?

PMID- 22872724
TI  - The effect of acceptance on health outcomes in patients with chronic kidney
      disease.
AB  - The concept of acceptance has both research and clinical significance. There may
      be two types of acceptance leading to different health outcomes. By assessing
      their level and type of acceptance, clinicians could provide patients with
      appropriate treatments to encourage 'active' acceptance, thereby leading to
      positive health outcomes.

PMID- 22872725
TI  - Detection and progression of chronic kidney disease: does the rear-view mirror
      help?

PMID- 22872726
TI  - Immunotactoid glomerulopathy: clinicopathologic and proteomic study.
AB  - BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare glomerular disease.
      Here, we report the largest clinicopathologic series of ITG and define its
      proteomic profile. METHODS: The characteristics of 16 ITG patients who were
      identified from our pathology archives are provided between 1993 and 2011. We
      also performed laser microdissection and mass spectrometry (LMD/MS) in three
      cases. RESULTS: Presentation included proteinuria (100%), nephrotic syndrome
      (69%), renal insufficiency (50%) and microhematuria (80%). Hypocomplementemia was
      present in 46% and a serum M-spike in 63%. Hematologic malignancy was present in
      38%, including chronic lymphocytic leukemia in 19%, lymphoplasmacytic lymphoma in
      13% and myeloma in 13%. The pattern of glomerular injury was
      membranoproliferative (56%), membranous (31%) or proliferative (13%)
      glomerulonephritis. The microtubular deposits were immunoglobulin light chain
      restricted in 69% and had a mean diameter of 31 nm (range 17-52). During an
      average of 48 months of follow-up for 12 patients, 50% had remission, 33% had
      persistent renal dysfunction and 17% progressed to end-stage renal disease.
      Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic
      light chains, complement factors of the classical and terminal pathway and small
      amount of serum amyloid P-component. CONCLUSIONS: Hematologic malignancy,
      particularly lymphoma, is not uncommon in ITG. ITG appears to have a better
      prognosis than other paraprotein-related renal lesions, with a half of patients
      expected to recover kidney function with immunosuppressive therapy or
      chemotherapy. The proteomic profile of ITG is consistent with deposition of
      monotypic immunoglobulins and activation of the classical and terminal pathway of
      complement.

PMID- 22872727
TI  - Pleiotropic effects of angiopoietin-2 deficiency do not protect mice against
      endotoxin-induced acute kidney injury.
AB  - BACKGROUND: In sepsis and various other inflammatory conditions, elevated
      circulating levels of angiopoietin-2 (Ang2) are detected, but the precise
      functional role of Ang2 in these conditions is not well understood. Here, we
      investigated the contribution of Ang2 to the inflammatory response and renal
      function impairment in a mouse model of endotoxaemia. METHODS: Ang2-deficient
      mice and wild-type littermates were challenged with lipopolysaccharide [LPS; 1500
      EU/g, intraperitoneal (i.p.)]. In additional experiments, wild-type C57Bl/6 mice
      were depleted of circulating neutrophils by antibody treatment (NIMPR14) prior to
      LPS challenge to study the role of neutrophils in regulating LPS-induced cytokine
      release. After 8 or 24 h of LPS challenge, the mice were sacrificed and organs
      were harvested. Quantitative reverse transcription polymerase chain reaction and
      enzyme-linked immunosorbent assay were performed for endothelial adhesion
      molecules (P-selectin, E-selectin, VCAM-1 and ICAM-1) and plasma cytokines (TNF
      alpha, IL-6, KC, MIP-2), respectively. To assess renal function, blood urea
      nitrogen levels in plasma and albumin-to-creatinine ratio in urine were measured.
      RESULTS Upon LPS challenge, expression levels of various endothelial adhesion
      molecules in Ang2-deficient mice were reduced in an organ-specific manner. In
      contrast, in these mice, plasma levels of TNF-alpha and IL-6 were significantly
      increased compared with their wild-type littermates, possibly due to decreased
      neutrophil glomerular influx. Importantly, the absence of Ang2 did not protect
      the mice from acute kidney injury (AKI) upon LPS challenge. CONCLUSIONS The
      absence of Ang2 release upon LPS challenge induces pleotropic effects with regard
      to endothelial activation and systemic inflammation, but does not protect mice
      from LPS-induced AKI.

PMID- 22872728
TI  - Exploring the relationships between patient characteristics and their dialysis
      care experience.
AB  - BACKGROUND: Previous studies have shown that it is possible for patient
      experience to be influenced by factors that are not attributable to health-care.
      Therefore, if patient experience is to be used as an accurate indicator of
      clinical performance, then it is important to understand its determinants.
      METHODS: We used data from 840 dialysis patients who completed a validated
      patient experience survey. We created a potential theoretical framework based on
      available clinical knowledge to hypothesize the relationships between 13
      demographic, socio-economic and health status factors and three outcome measures:
      global rating of the dialysis centre and the patient experience with the
      nephrologist's and nurses' care. The theoretical framework guided the selection
      of confounding variables for each determinant, which were then entered as terms
      in multivariable linear regression models. RESULTS: Patients who were of older
      age, of non-European decent, and who had a lower educational level, lower albumin
      level, with better self-rated health and who were without co-morbidities reported
      higher global ratings with the dialysis centre than their counterparts. Past
      myocardial infarction and better self-rated health were found to be determinants
      of a more positive experience while in the nephrologist's care. A more positive
      experience with nurses' care was associated with factors including older age,
      Dutch origin background, lower educational level, lower albumin levels and better
      self-rated health. CONCLUSIONS: Several characteristics of dialysis patients
      influence the way they rate and experience their care. When using the patient
      experience and ratings as indicators of clinical performance, they should be
      adjusted for such factors as identified in our study. This will facilitate a
      meaningful comparison of dialysis centres, and enable informed decision making by
      patients, insurers and policy makers.

PMID- 22872729
TI  - Escherichia coli 83972 expressing a P fimbriae oligosaccharide receptor mimic
      impairs adhesion of uropathogenic E. coli.
AB  - Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC)
      are a significant health concern, exacerbated by the rapid emergence of multidrug
      resistant strains refractory to antibiotic treatment. P fimbriae are strongly
      associated with upper urinary tract colonization due to specific binding to alpha
      D-galactopyranosyl-(1-4)-beta-D-galactopyranoside receptors in the kidneys. Thus,
      inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E.
      coli 83972 is an asymptomatic bacteriuria isolate successfully used as a
      prophylactic agent to prevent UTI in human studies. We constructed a recombinant
      E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae
      receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG
      adhesin variants. The recombinant strain, E. coli 83972::lgtCE, impaired P
      fimbriae-mediated adhesion to human erythrocytes and kidney epithelial cells.
      Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse
      UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.

PMID- 22872730
TI  - Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus
      strains in 5 children: a case series.
AB  - Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens
      from 5 of 106 (4.7%) immunocompetent children who required treatment for
      rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010.
      Four strains were related to pentavalent rotavirus vaccine, whereas one was
      related to monovalent rotavirus vaccine. The contribution of these strains to
      each patient's illness was unclear given that 2 patients had prominent
      respiratory symptoms and 2 were concurrently infected with another pathogen
      (group F adenovirus and norovirus). Continued monitoring is necessary to assess
      the role of vaccine strains and vaccine-reassortant strains in pediatric
      rotavirus infections.

PMID- 22872731
TI  - Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant
      of influenza A virus subtype H3N2 (H3N2v).
AB  - BACKGROUND: Cases of infection due to a novel swine-origin variant of influenza A
      virus subtype H3N2 (H3N2v) have recently been identified in the United States,
      primarily among children. We estimate levels of cross-reactive antibody to H3N2v
      by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV),
      with or without adjuvant, may increase seroprotection. METHODS: Antibody to H3N2v
      was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by
      microneutralization assay. Seroprevalence and seroprotection were defined as an
      HI titer of >=40, and levels were compared with those for ancestral and
      contemporary human strains. The analysis included 1116 sera collected during fall
      2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced
      antibody levels were also assessed in sera from 136 children aged <10 years and
      65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in
      sera from 182 elderly individuals aged >=65 years before and after receipt of
      2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or
      unadjuvanted subunit TIV (for 79). RESULTS: The overall prevalence of HI titers
      of >=40 against A(H3N2)v was 25%. No children aged <5 years and <20% of
      individuals aged <=14 years or >=40 years had an HI titer of >=40. Conversely,
      among individuals aged 15-39 years, half of teens and adults showed H3N2v
      seroprotection. Following TIV receipt, <15% of individuals in any vaccine group
      developed a 4-fold increase in antibody level. CONCLUSIONS: A substantial
      proportion of adolescents and young adults have cross-reactive antibody against
      emerging H3N2v, whereas children and older adults show broad susceptibility.
      Recent formulations of TIV do not substantially increase seroprotection. A
      specific vaccine would be needed if H3N2v establishes epidemic spread. CLINICAL
      TRIALS REGISTRATION: NCT01140009 and NCT01368796.

PMID- 22872732
TI  - Reevaluation of epidemiological data demonstrates that it is consistent with
      cross-immunity among human papillomavirus types.
AB  - BACKGROUND: The degree of cross-immunity between human papillomavirus (HPV) types
      is fundamental both to the epidemiological dynamics of HPV and to the impact of
      HPV vaccination. Epidemiological data on HPV infections has been repeatedly
      interpreted as inconsistent with cross-immunity. METHODS: We reevaluate the
      epidemiological data using a model to determine the odds ratios of multiple to
      single infections expected in the presence or absence of cross-immunity. We
      simulate a virtual longitudinal survey to determine the effect cross-immunity has
      on the prevalence of multiple infections. We calibrate our model to
      epidemiological data and estimate the extent of type replacement following
      vaccination against specific HPV types. RESULTS: We find that cross-immunity can
      produce odds ratios of infection comparable with epidemiological observations. We
      show that the sample sizes underlying existing surveys have been insufficient to
      identify even intense cross-immunity. We also find that the removal of HPV type
      16, type 18, and types 6 and 11 would increase the prevalence of nontargeted
      types by 50%, 29%, and 183%, respectively. CONCLUSIONS: Cross-immunity between
      HPV types is consistent with epidemiological data, contrary to previous
      interpretations. Cross-immunity may cause significant type replacement following
      vaccination, and therefore should be considered in future vaccine studies and
      epidemiological models.

PMID- 22872733
TI  - Influence of host genetics and environment on nasal carriage of staphylococcus
      aureus in danish middle-aged and elderly twins.
AB  - BACKGROUND: Nasal carriage is a major risk factor for Staphylococcus aureus
      infection. Approximately, one-quarter of adults carry S. aureus. However, the
      role of host genetics on S. aureus nasal carriage is unknown. METHODS: Nasal
      swabs were obtained from a national cohort of middle-aged and elderly Danish
      twins. Subjects colonized with S. aureus were identified by growth on selective
      plates and spa typing. A second sample was obtained from twins initially
      concordant for carriage. Twins found to again be colonized with S. aureus were
      defined as persistent carriers. RESULTS: The prevalence of S. aureus carriage
      among 617 twin pairs (monozygotic/dizygotic pairs: 112/505) was 26.3% (95%
      confidence interval [CI], 24.0%-28.9%). The concordance rate for carriage did not
      differ significantly between pairs of monozygotic (37.5%; 95% CI, 22.3%-53.8%)
      twins and same sex (24.2%; 95% CI, 15.4%-34.5%), and opposite sex (21.4%; 95% CI,
      12.0%-33.4%) dizygotic twins. Despite shared childhoods, only 1 of 617 pairs was
      concordant with respect to lineage. Although heritability increased for S. aureus
      and lineage persistency, no significant heritability was detected. CONCLUSION: In
      this study, host genetic factors exhibited only a modest influence on the S.
      aureus carrier state of middle-aged and elderly individuals.

PMID- 22872734
TI  - A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella
      zoster glycoprotein e subunit vaccine candidate in young and older adults.
AB  - BACKGROUND: An adjuvanted recombinant varicella zoster virus (VZV) subunit
      vaccine is being developed for the prevention of herpes zoster and its
      complications. METHODS: In a phase I/II, open-label, randomized, parallel-group
      study, older adults (50-70 years) received 2 doses 2 months apart of an
      adjuvanted recombinant glycoprotein E vaccine (HZ/su; n = 45), a live attenuated
      Oka strain VZV vaccine (OKA; n = 45), or HZ/su and OKA administered concomitantly
      (n = 45). To evaluate safety prior to administration in older adults, young
      adults (18-30 years) were vaccinated with 2 doses 2 months apart of HZ/su (n =
      10) or OKA (n = 10). Safety and immunogenicity were assessed up to 42 months for
      older adults immunized with HZ/su and up to 12 months for all others. RESULTS:
      Few grade 3 events and no severe adverse events were reported. Fatigue, myalgia,
      headache, and injection site pain were the most common solicited reactions for
      HZ/su and occurred more frequently than with OKA. CD4(+) T-cell and humoral
      immune responses were much higher with HZ/su than with OKA and remained elevated
      until 42 months. Addition of OKA to HZ/su did not increase immunogenicity.
      CONCLUSIONS: In this study, HZ/su adjuvanted subunit vaccine was well tolerated
      and more immunogenic than a live attenuated VZV vaccine. Clinical Trial
      registration. NCT00492648 and NCT00492648.

PMID- 22872735
TI  - Staphylococcus aureus leukotoxin GH promotes inflammation.
AB  - BACKGROUND: Staphylococcus aureus produces numerous molecules that facilitate
      survival in the host. We recently identified a novel S. aureus leukotoxin
      (leukotoxin GH [LukGH]) using proteomics, but its role in virulence remains
      unclear. Here we investigated the role of LukGH in vivo. METHODS: We tested
      cytotoxicity of LukGH toward polymorphonuclear leukocytes (PMNs) from mice,
      rabbits, monkeys, and humans. LukGH was administered to mice, rabbits, and a
      cynomolgus monkey by subcutaneous or intradermal injection to assess cytotoxicity
      or host response in vivo. The effects of LukGH in vivo were compared with those
      of Panton-Valentine leukocidin (PVL), a well-characterized S. aureus leukotoxin.
      The contribution of LukGH to S. aureus infection was tested using mouse and
      rabbit infection models. RESULTS: Susceptibility of PMNs to LukGH was similar
      between humans and cynomolgus monkeys, and was greater than that of rabbits,
      which in turn was greater than that of mice. LukGH or PVL caused skin
      inflammation in rabbits and a monkey, but deletion of neither lukGH nor lukGH and
      lukS/F-PV reduced severity of USA300 infections in rabbits or mice. Rather, some
      disease parameters (eg, rabbit abscess size) were increased following infection
      with a lukGH and lukS/F-PV deletion strain. CONCLUSIONS: Our findings indicate
      that S. aureus leukotoxins enhance the host inflammatory response and influence
      the outcome of infection.

PMID- 22872736
TI  - Prevalence and clinical impact of norovirus fecal shedding in children with
      inherited immune deficiencies.
AB  - We report the first prospective study describing the prevalence and clinical
      consequences of norovirus infection in hospitalized children with primary
      immunodeficiencies. Fecal samples from 62 children were systematically screened
      for virus. Norovirus was the most frequent pathogen (11 of 24 positive samples)
      found in both combined and humoral immunocompromised children. Norovirus shedding
      was associated with gastrointestinal symptoms and concomitant viremia in 54.5%
      and 25% of cases, respectively. Norovirus excretion was prolonged: 57.1% of fecal
      samples were still positive after a median of 9.5-months follow-up. Further large
      longitudinal studies are needed to evaluate the clinical consequences of
      norovirus shedding in patients with primary immunodeficiencies.

PMID- 22872737
TI  - Distinct phases of blood gene expression pattern through tuberculosis treatment
      reflect modulation of the humoral immune response.
AB  - BACKGROUND: Accurate assessment of treatment efficacy would facilitate clinical
      trials of new antituberculosis drugs. We hypothesized that early alterations in
      peripheral immunity could be measured by gene expression profiling in
      tuberculosis patients undergoing successful conventional combination treatment.
      METHODS: Ex vivo blood samples from 27 pulmonary tuberculosis patients were
      assayed at diagnosis and during treatment. RNA was processed and hybridized to
      Affymetrix GeneChips, to determine expression of over 47,000 transcripts.
      RESULTS: There were significant >= 2-fold changes in expression of >4000 genes
      during treatment. Rapid, large-scale changes were detected, with down-regulated
      expression of 1261 genes within the first week, including inflammatory markers
      such as complement components C1q and C2. This was followed by slower changes in
      expression of different networks of genes, including a later increase in
      expression of B-cell markers, transcription factors, and signaling molecules.
      CONCLUSIONS: The fast initial down-regulation of expression of inflammatory
      mediators coincided with rapid killing of actively dividing bacilli, whereas
      slower delayed changes occurred as drugs acted on dormant bacilli and coincided
      with lung pathology resolution. Measurement of biosignatures during clinical
      trials of new drugs could be useful predictors of rapid bactericidal or
      sterilizing drug activity, and would expedite the licensing of new treatment
      regimens.

PMID- 22872738
TI  - Usefulness of 3'-deoxy-3'-18F-fluorothymidine PET for predicting early response
      to chemoradiotherapy in head and neck cancer.
AB  - This study compared the utility of 3'-deoxy-3'-(18)F-fluorothymidine PET ((18)F
      FLT PET) with that of (18)F-FDG PET for assessment of the early locoregional
      clinical outcomes of chemoradiotherapy for head and neck squamous cell
      carcinomas. METHODS: From May 2006 to September 2010, 28 patients with head and
      neck squamous cell carcinomas underwent (18)F-FLT and (18)F-FDG PET before
      radiation therapy (RT), 4 wk after the initiation of RT, and 5 wk after
      completion of RT. PET images were evaluated qualitatively for regions of focally
      increased metabolism and were analyzed in relation to residual accumulation and
      local disease control. RESULTS: During RT, (18)F-FLT uptake decreased more
      significantly than (18)F-FDG uptake. (18)F-FLT accumulations disappeared in 34 of
      54 lesions (63%), and negative predictive value was 97%. (18)F-FDG PET during RT
      also had a high negative predictive value (100%), but only 9 lesions (16%) showed
      complete absence of accumulation. The specificity and overall accuracy of (18)F
      FLT PET were significantly higher than those of (18)F-FDG PET both during and
      after RT. In particular, high significance was attributable to the results of the
      evaluations of primary lesions. There were significant differences in 3-y local
      control between the residual-accumulation and no-accumulation groups on both
      posttreatment (18)F-FLT PET (P < 0.0001) and posttreatment (18)F-FDG PET (P =
      0.0081). CONCLUSION: (18)F-FLT PET during RT and early follow-up facilitates the
      selection of optimal further therapy and the prediction of outcomes.

PMID- 22872739
TI  - Direct quantification of left ventricular motion and thickening changes using
      rest-stress myocardial perfusion SPECT.
AB  - Changes in myocardial wall motion and thickening during myocardial perfusion
      SPECT are typically assessed separately from gated studies for the presence of
      stress-induced functional abnormalities. We sought to develop and validate a
      novel approach for automatic quantification of rest-stress myocardial motion and
      thickening changes (MTCs). METHODS: Endocardial surfaces at the end-diastolic and
      end-systolic frames for rest-stress studies were registered automatically to each
      other by matching ventricular surfaces. Myocardial MTCs were computed, and normal
      limits of change were determined as the mean and SD for each polar sample. Normal
      limits were used to quantify the MTCs for each map, and the accumulated sample
      values were used for abnormality assessments in segmental regions. A hybrid
      method was devised by combining the total perfusion deficit (TPD) and MTC for
      each vessel territory. Normal limits were obtained from 100 subjects with low
      likelihood of coronary artery disease. For validation, 623 subjects with
      correlating invasive angiography were studied. All subjects underwent a rest
      stress (99m)Tc-sestamibi exercise or adenosine test and coronary angiography
      within 3 months of myocardial perfusion SPECT. All MTC and TPD measurements were
      derived automatically. The diagnostic accuracy for detection of coronary artery
      disease for MTC plus TPD was compared with TPD alone. RESULTS: Segmental normal
      values were between -1.3 and -4.1 mm for motion change and between -30.1% and 
      9.8% for thickening change. MTC combined with TPD achieved 61% sensitivity for 3
      vessel-disease (3VD), 63% for 2-vessel-disease (2VD), and 90% for 1-vessel
      disease (1VD) detection, compared with 32% for 3VD (P < 0.0001), 53% for 2VD (P <
      0.001), and 90% for 1VD (P = 1.0) detection using the TPD-alone method. The
      specificity for the combined method was 71% for 3VD, 72% for 2VD, and 47% for 1VD
      detection versus 90% for 3VD (P < 0.0001), 80% for 2VD (P < 0.001), and 50% for
      1VD detection (P = 0.0625) for the TPD-alone method. The accuracy of 3VD
      detection by MTC plus TPD was higher (69%) than the accuracy of TPD plus change
      in ejection fraction (63%) (P < 0.004). CONCLUSION: We established normal limits
      and a novel method for computation of regional functional changes between the
      rest and poststress studies. Compared with TPD alone, the combination of TPD with
      MTC improved the sensitivity for the detection of 3VD and 2VD.

PMID- 22872740
TI  - Differential effects of predosing on tumor and tissue uptake of an 111In-labeled
      anti-TENB2 antibody-drug conjugate.
AB  - TENB2, also known as tomoregulin or transmembrane protein with epidermal growth
      factor-like and 2 follistatin-like domains, is a transmembrane proteoglycan
      overexpressed in human prostate tumors. This protein is a promising target for
      antimitotic monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADC)
      therapy. Nonlinear pharmacokinetics in normal mice suggested that antigen
      expression in normal tissues may contribute to targeted mediated disposition. We
      evaluated a predosing strategy with unconjugated antibody to block ADC uptake in
      target-expressing tissues in a mouse model while striving to preserve tumor
      uptake and efficacy. METHODS: Unconjugated, unlabeled antibody was
      preadministered to mice bearing the TENB2-expressing human prostate explant
      model, LuCaP 77, followed by a single administration of (111)In-labeled anti
      TENB2-MMAE for biodistribution and SPECT/CT studies. A tumor-growth-inhibition
      study was conducted to determine the pharmacodynamic consequences of predosing.
      RESULTS: Preadministration of anti-TENB2 at 1 mg/kg significantly increased blood
      exposure of the radiolabeled ADC and reduced intestinal, hepatic, and splenic
      uptake while not affecting tumor accretion. Similar tumor-to-heart ratios were
      measured by SPECT/CT at 24 h with and without the predose. Consistent with this,
      the preadministration of 0.75 mg/kg did not interfere with efficacy in a tumor
      growth study dosed at 0.75 mg or 2.5 mg of ADC per kilogram. CONCLUSION: Overall,
      the potential to mask peripheral, nontumor antigen uptake while preserving tumor
      uptake and efficacy could ameliorate toxicity and may significantly affect future
      dosing strategies for ADCs.

PMID- 22872741
TI  - Positron lymphography: multimodal, high-resolution, dynamic mapping and resection
      of lymph nodes after intradermal injection of 18F-FDG.
AB  - The lymphatic system plays a critical role in the maintenance of healthy tissues.
      Its function is an important indicator of the presence and extent of disease. In
      oncology, metastatic spread to local lymph nodes (LNs) is a strong predictor of
      poor outcome. Clinical methods for the visualization of LNs involve regional
      injection and tracking of (99m)Tc-sulfur colloid ((99m)Tc-SC) along with
      absorbent dyes. Intraoperatively, these techniques suffer from the requirement of
      administration of multiple contrast media ((99m)Tc-SC and isosulfan blue),
      unwieldy gamma-probes, and a short effective surgical window for dyes.
      Preclinically, imaging of transport through the lymphatics is further hindered by
      the resolution of lymphoscintigraphy and SPECT. We investigated multimodal
      imaging in animal models using intradermal administration of (18)F-FDG for
      combined diagnostic and intraoperative use. PET visualizes LNs with high
      sensitivity and resolution and low background. Cerenkov radiation (CR) from (18)F
      FDG was evaluated to optically guide surgical resection of LNs. METHODS: Imaging
      of (18)F-FDG uptake used PET and sensitive luminescent imaging equipment (for
      CR). Dynamic PET was performed in both sexes and multiple strains (NCr Nude,
      C57BL/6, and Nu/Nu) of mice. Biodistribution confirmed the uptake of (18)F-FDG
      and was compared with that of (99m)Tc-SC. Verification of uptake and the ability
      to use (18)F-FDG CR to guide nodal removal were confirmed histologically.
      RESULTS: Intradermal injection of (18)F-FDG clearly revealed lymphatic vessels
      and LNs by PET. Dynamic imaging revealed rapid and sustained labeling of these
      structures. Biodistribution of the radiotracer confirmed the active transport of
      radioglucose in the lymphatics to the local LNs and over time into the general
      circulation. (18)F-FDG also enabled visualization of LNs through CR, even before
      surgically revealing the site, and guided LN resection. CONCLUSION: Intradermal
      (18)F-FDG can enhance the preclinical investigation of the lymphatics through
      dynamic, high-resolution, and quantitative tomographic imaging. Clinically,
      combined PET/Cerenkov imaging has significant potential as a single-dose, dual
      modality tracer for diagnostics (PET/CT) and guided resection of LNs (Cerenkov
      optical).

PMID- 22872742
TI  - Role of O-(2-(18)F-fluoroethyl)-L-tyrosine PET for differentiation of local
      recurrent brain metastasis from radiation necrosis.
AB  - The aim of this study was to investigate the potential of O-(2-(18)F-fluoroethyl)
      L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis
      from radiation necrosis after radiation therapy because the use of contrast
      enhanced MRI for this issue is often difficult. METHODS: Thirty-one patients
      (mean age +/- SD, 53 +/- 11 y) with single or multiple contrast-enhancing brain
      lesions (n = 40) on MRI after radiation therapy of brain metastases were
      investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios
      (TBR(max) and TBR(mean), respectively; 20-40 min after injection) of (18)F-FET
      uptake were determined. Time-activity curves were generated, and the time to peak
      (TTP) was calculated. Furthermore, time-activity curves of each lesion were
      assigned to one of the following curve patterns: (I) constantly increasing (18)F
      FET uptake, (II) (18)F-FET uptake peaking early (TTP <= 20 min) followed by a
      plateau, and (III) (18)F-FET uptake peaking early (TTP <= 20 min) followed by a
      constant descent. The diagnostic accuracy of the TBR(max) and TBR(mean) of (18)F
      FET uptake and the curve patterns for the correct identification of recurrent
      brain metastasis were evaluated by receiver-operating-characteristic analyses or
      Fisher exact test for 2 * 2 contingency tables using subsequent histologic
      analysis (11 lesions in 11 patients) or clinical course and MRI findings (29
      lesions in 20 patients) as reference. RESULTS: Both TBR(max) and TBR(mean) were
      significantly higher in patients with recurrent metastasis (n = 19) than in
      patients with radiation necrosis (n = 21) (TBR(max), 3.2 +/- 0.9 vs. 2.3 +/- 0.5,
      P < 0.001; TBR(mean), 2.1 +/- 0.4 vs. 1.8 +/- 0.2, P < 0.001). The diagnostic
      accuracy of (18)F-FET PET for the correct identification of recurrent brain
      metastases reached 78% using TBR(max) (area under the ROC curve [AUC], 0.822 +/-
      0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P = 0.001), 83% using
      TBR(mean) (AUC, 0.851 +/- 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95;
      P < 0.001), and 92% for curve patterns II and III versus curve pattern I
      (sensitivity, 84%; specificity, 100%; P < 0.0001). The highest accuracy (93%) to
      diagnose local recurrent metastasis was obtained when both a TBR(mean) greater
      than 1.9 and curve pattern II or III were present (AUC, 0.959 +/- 0.03;
      sensitivity, 95%; specificity, 91%; P < 0.001). CONCLUSION: Our findings suggest
      that the combined evaluation of the TBR(mean) of (18)F-FET uptake and the pattern
      of the time-activity curve can differentiate local brain metastasis recurrence
      from radionecrosis with high accuracy. (18)F-FET PET may thus contribute
      significantly to the management of patients with brain metastases.

PMID- 22872743
TI  - Comparison of mAbs targeting epithelial cell adhesion molecule for the detection
      of prostate cancer lymph node metastases with multimodal contrast agents:
      quantitative small-animal PET/CT and NIRF.
AB  - The proliferation of most carcinomas is associated with an overexpression of
      epithelial cell adhesion molecule (EpCAM), a 40-kDa type I transmembrane protein
      found on epithelial cells yet absent from other cell types. The absence of EpCAM
      in normal lymphatics makes it an attractive marker for studying lymph node (LN)
      metastases of carcinomas to improve LN staging accuracy. Herein, we developed and
      quantitatively compared dual-labeled monoclonal antibodies (mAbs) of varying
      affinities against EpCAM for both noninvasive and intraoperative detection of
      metastatic LNs in prostate cancer. METHODS: A panel of hybridoma-derived anti
      EpCAM mAbs was generated and screened. Two high-affinity candidate mAbs with
      specificity for nonoverlapping epitopes on the EpCAM extracellular domain were
      chosen for further evaluation. After conjugation with DOTA for (64)Cu
      radiolabeling and IRDye 800CW as a fluorophore, dual-labeled specific or isotype
      control mAb was administered intravenously to male nu/nu mice at 10-12 wk after
      orthotopic implantation of DsRed-expressing PC3 cells. Within 18-24 h,
      noninvasive small-animal PET/CT and in vivo, in situ, and ex vivo DsRed reporter
      gene and near-infrared fluorescence (NIRF) imaging were performed to detect
      primary tumors and metastatic LNs. Using DsRed fluorescence as the true indicator
      of cancer-positive tissue, we performed receiver operating characteristic curve
      analyses of percentage injected dose per gram measured from quantitative small
      animal PET/CT and fluorescence intensity measured from semiquantitative NIRF
      imaging for each LN examined to compare mAb sensitivity and specificity. RESULTS:
      mAbs 7 and 153 generated in-house were found to have higher affinity than
      commercial mAb 9601. Accuracy, as a function of sensitivity and specificity, for
      the detection of cancer-positive LNs during in vivo small-animal PET/CT was
      highest for mAbs 7 (87.0%) and 153 (78.0%) and significantly greater (P < 0.001)
      than random chance (50.0%). Rates for mAb 9601 (60.7%) and control mAb 69 (27.0%)
      were not significantly different from chance. Similarly, mAb 7 had significant
      detection accuracy by NIRF imaging (96.0%, P < 0.001). CONCLUSION: mAbs 7 and 153
      are attractive, high-affinity candidates for further multimodal imaging agent
      optimization aimed at enhancing sensitivity and specificity for detection of
      metastatic LNs in prostate cancer. Fully quantitative NIRF imaging is needed for
      comprehensive analyses of NIRF-labeled agent accuracy for intraoperative
      guidance.

PMID- 22872744
TI  - HER2-positive tumors imaged within 1 hour using a site-specifically 11C-labeled
      Sel-tagged affibody molecule.
AB  - A rapid, reliable method for distinguishing tumors or metastases that overexpress
      human epidermal growth factor receptor 2 (HER2) from those that do not is highly
      desired for individualizing therapy and predicting prognoses. In vivo imaging
      methods are available but not yet in clinical practice; new methodologies
      improving speed, sensitivity, and specificity are required. METHODS: A HER2
      binding Affibody molecule, Z(HER2:342), was recombinantly fused with a C-terminal
      selenocysteine-containing tetrapeptide Sel-tag, allowing site-specific labeling
      with either (11)C or (68)Ga, followed by biodistribution studies with small
      animal PET. Dosimetry data for the 2 radiotracers were compared. Imaging of HER2
      expressing human tumor xenografts was performed using the (11)C-labeled Affibody
      molecule. RESULTS: Both the (11)C- and (68)Ga-labeled tracers initially cleared
      rapidly from the blood, followed by a slower decrease to 4-5 percentage injected
      dose per gram of tissue at 1 h. Final retention in the kidneys was much lower (>5
      fold) for the (11)C-labeled protein, and its overall absorbed dose was
      considerably lower. (11)C-Z(HER2:342) showed excellent tumor-targeting
      capability, with almost 10 percentage injected dose per gram of tissue in HER2
      expressing tumors within 1 h. Specificity was demonstrated by preblocking binding
      sites with excess ligand, yielding significantly reduced radiotracer uptake (P =
      0.002), comparable to uptake in tumors with low HER2 expression. CONCLUSION: To
      our knowledge, the Sel-tagging technique is the first that enables site-specific
      (11)C-radiolabeling of proteins. Here we present the finding that, in a favorable
      combination between radionuclide half-life and in vivo pharmacokinetics of the
      Affibody molecules, (11)C-labeled Sel-tagged Z(HER2:342) can successfully be used
      for rapid and repeated PET studies of HER2 expression in tumors.

PMID- 22872745
TI  - Complications and management of an implanted intraperitoneal access port system
      for intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis.
AB  - OBJECTIVE: The efficacy of intraperitoneal chemotherapy for gastric cancer with
      peritoneal metastasis has been verified by clinical trials. To perform
      intraperitoneal chemotherapy safely and effectively, the appropriate management
      of intraperitoneal access ports is essential. The aim of this study was to
      investigate the occurrence of port complications during cyclically repeated
      intraperitoneal chemotherapy. METHODS: The medical records of 131 gastric cancer
      patients with peritoneal metastases who received intraperitoneal paclitaxel
      between 2005 and 2011 were retrospectively analyzed. RESULTS: The median period
      of intraperitoneal chemotherapy using a port system was 12.9 months (range: 0.8
      61.5 months), and a total of 27 (20.6%) patients experienced port complications.
      Inflow obstruction (7.6%) and infection (6.9%) were the main complications,
      followed by reflux (3.1%), subcutaneous masses (1.5%) and fistulae (1.5%). The
      median interval between port implantation and port complication was 5.4 months
      (range: 0.3-40.9 months). Complications were controllable and chemotherapy was
      not terminated by complications. Survival was not affected by the presence or
      absence of port complications (median survival time: 22.5 vs. 17.2 months,
      respectively; P=0.65). CONCLUSIONS: Intraperitoneal chemotherapy for gastric
      cancer using a port is safe and feasible under appropriate management.

PMID- 22872746
TI  - Hypomanic episode during recurrent gastric cancer treatment: report of a rare
      case and literature review.
AB  - S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer.
      While depression and delirium are frequent in cancer patients, hypomania during
      chemotherapy is rare. We describe a rare case of hypomania during S-1 plus
      cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no
      previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric
      cancer. She showed peculiar behavior. Physical examination, urine, blood and
      imaging findings were normal. There was no gastric cancer progression. During
      psychiatric consultation, she behaved inappropriately. However, she behaved
      normally while performing daily activities. She manifested a persistently
      elevated, expansive or irritable mood, clearly different from her usual non
      depressed state, meeting hypomania diagnostic criteria. Her condition did not
      require chemotherapy discontinuation or additional medication. During the second
      and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients
      often have adjustment disorders, depression and delirium, but rarely hypomania.
      Our patient showed no significant changes in blood biochemistry and brain and
      whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be
      excluded, hypomanic symptoms did not improve during the chemotherapy rest period,
      nor was there deterioration during subsequent cycles, suggesting drug-induced
      mania to be unlikely. Possible onset mechanisms include manic defense phenomena,
      common with stressful life events. There are no reports of recurrent gastric
      cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy,
      i.e. our patient represents a rare course. Clinicians should recognize psychosis
      or mood disorders during gastric cancer treatment. Further accumulation of such
      rare cases might elucidate pathological mechanisms underlying hypomania in cancer
      patients.

PMID- 22872747
TI  - Seeking an academic pharmacy career.

PMID- 22872748
TI  - Safe use of hemodialysis for dabigatran removal before cardiac surgery.
AB  - OBJECTIVE: To describe a case in which hemodialysis was performed before cardiac
      transplantation in an attempt to reverse the effects of dabigatran and reduce the
      risk of bleeding associated with surgery. CASE SUMMARY: A 59-year-old female with
      heart failure and atrial fibrillation was admitted for orthotropic heart
      transplant. She had been stable at home with continuous milrinone therapy 0.25
      MUg/kg/min, amiodarone 200 mg twice daily, and dabigatran 150 mg twice daily for
      stroke prevention secondary to atrial fibrillation. Upon notification of organ
      availability, the patient was admitted to the hospital for transplant surgery,
      with her last dose of dabigatran taken approximately 36 hours before admission.
      Coagulation studies indicated normal activated partial thromboplastin time,
      slightly elevated international normalized ratio of 1.2, and elevated thrombin
      time (TT) of 90.6 seconds (upper limit of normal 19.9 seconds). A hemodialysis
      catheter was emergently placed and dialysis was initiated. One hour after
      initiation, TT decreased to 65.5 seconds. After 2.5 hours of dialysis, TT further
      decreased to 60.2 seconds; at that time, the patient underwent transplantation
      with no abnormal bleeding during or following surgery. DISCUSSION: Minimal data
      exist on techniques to reverse the effects of dabigatran in cases of bleeding or
      emergent surgery. This case examines the efficacy of hemodialysis to decrease
      dabigatran's effect on clotting assays prior to surgery to reduce the risk of
      bleeding. In this case, a TT of 60.2 seconds with recent dabigatran
      administration did not result in abnormal bleeding associated with cardiac
      surgery. CONCLUSIONS: To our knowledge, this case report represents the first
      published data on the effects of hemodialysis on dabigatran removal and reversal
      of anticoagulation associated with dabigatran before surgery. The routine use of
      preoperative hemodialysis in patients on dabigatran is not recommended; however,
      the potential efficacy in such circumstances is supported by the successful
      results in this case.

PMID- 22872749
TI  - Impact of enteral methadone on the ability to wean off continuously infused
      opioids in critically ill, mechanically ventilated adults: a case-control study.
AB  - BACKGROUND: Continuously infused opioids are frequently used to optimize patient
      comfort in the intensive care unit (ICU). However, concerns about rebound pain
      and opioid withdrawal may delay efforts to discontinue this therapy. OBJECTIVE:
      To measure the association between use of scheduled enteral methadone according
      to a protocol in mechanically ventilated, medical critically ill adults receiving
      prolonged continuously infused fentanyl and the time to discontinue continuously
      infused fentanyl therapy. METHODS: This case-control study included 20
      consecutive mechanically ventilated adults in a medical ICU, without a history of
      chronic opioid use, who received 72 or more hours of continuously infused
      fentanyl and were prescribed scheduled enteral methadone as part of a protocol
      medical ICU strategy to wean off continuously infused fentanyl. Patients were
      matched in a 1:2 fashion, by duration of mechanical ventilation, to 40
      consecutive preprotocol medical ICU patients meeting the same criteria but who
      were never given methadone. Duration of continuously infused fentanyl was
      compared between the 2 groups by constructing Kaplan-Meier plots and estimating
      the likelihood that methadone use was associated with a decrease in continuously
      infused fentanyl requirements over time, using a Cox proportional hazards model.
      RESULTS: The groups were well matched except the methadone patients were older (p
      = 0.04). Time (median [interquartile range]) to continuously infused fentanyl
      discontinuation was shorter in the methadone group (4.5 [3.9-5.8] vs 7.0 [4.9
      11.5] days; p = 0.002). Continuously infused fentanyl was more likely to be
      discontinued 2 days after methadone was first initiated (hazard ratio 9.1; p =
      0.0004). The proportion of patients who experienced 1 or more episodes of either
      QTc interval prolongation (p = 0.79) or unarousability (p = 0.47) was similar
      between the groups. CONCLUSIONS: Enterally administered methadone is associated
      with earlier cessation of continuously infused fentanyl in mechanically
      ventilated adults without a history of opioid dependence admitted to a medical
      ICU. Prospective, controlled studies are needed to further evaluate the safety
      and efficacy of methadone as a strategy to wean off continuously infused fentanyl
      in different ICU populations.

PMID- 22872750
TI  - Medication use and associated risk of falling in a geriatric outpatient
      population.
AB  - BACKGROUND: Studies have shown that approximately one third of community-dwelling
      people aged 65 years and older will experience a fall each year. Many studies
      indicate that use of multiple medications may put patients at an increased risk
      of falling, but few studies have been conducted to correlate the number of
      medications with the risk of falls. OBJECTIVE: To determine the medications most
      frequently used in patients aged 65 years or older who have experienced a fall
      within the past year, with particular attention to type or number of medications
      most commonly associated with multiple falls or a fall with injury. METHODS: We
      conducted a chart review in an outpatient internal medicine clinic over a 13
      month period. A total of 118 patients 65 years of age or older who were taking 4
      or more medications and had experienced at least 1 fall in the previous 12 months
      were included. Data relating to sex, age, race, diagnoses, medications, and
      number and type of falls were obtained during the chart review. The primary end
      point of the study was number and type of medications most commonly used in
      patients experiencing a fall. RESULTS: A total of 116 patients were examined for
      trends in fall risk. A logistic regression model and receiver operating
      characteristic curve demonstrated significant fall risk with the addition of
      medications, with patients experiencing a 14% increase in fall risk with the
      addition of each medication beyond a 4-medication regimen (OR 1.14; 95% CI 1.02
      to 1.27; p = 0.027). CONCLUSIONS: The addition of medications is associated with
      a significant increase in risk of falls in elderly patients, regardless of drug
      class. Further studies are needed to assess the possible increased risk of falls
      with increasing number of medications.

PMID- 22872751
TI  - Poor absorption of high-dose posaconazole in pediatric bone marrow transplant
      patients.
AB  - OBJECTIVE: To describe the use of high-dose posaconazole in 2 pediatric patients
      who received bone marrow transplant (BMT) and highlight concerns regarding
      posaconazole absorption. CASE SUMMARY: We present 2 pediatric BMT patients in
      whom prescribed high doses of posaconazole (120-300 mg/kg/day for >3 months)
      provided serum concentrations less than 1 MUg/mL. Both patients received
      posaconazole with other antifungal therapy and surgical debridement for Rhizopus
      spp. infections after allogeneic BMTs. Various alternative dosing strategies to
      potentially enhance posaconazole absorption to increase serum concentrations were
      attempted, including higher daily doses, frequent or continuous oral
      administration via feeding tube, use of enteral nutrition, and limiting use of
      acid-blocking agents. During high-dose therapy, frequent posaconazole serum
      concentration measurement and other monitoring techniques, such as continuous
      telemetry, were used. While the fungal infections resolved in both patients and
      no serious adverse effects could be attributed to high-dose posaconazole
      administration, posaconazole therapy may have contributed to nausea and vomiting
      in 1 of the patients. DISCUSSION: These 2 cases describe complex circumstances,
      with several reasons that may have affected the patients' posaconazole serum
      concentrations. Both patients received significantly higher doses than those
      recommended in the posaconazole prescribing information, but potentially serious
      adverse events were not observed since serum concentration measurements were
      rarely more than 0.5 MUg/mL. CONCLUSIONS: The safety of high-dose posaconazole
      therapy was not determined in these 2 patients. However, given that limited
      alternative therapy options are available for severely ill patients with
      suspected posaconazole malabsorption, research regarding dosing strategies should
      be considered.

PMID- 22872752
TI  - Pharmacists' recommendations to improve care transitions.
AB  - BACKGROUND: Increasingly, hospitals are implementing multifaceted programs to
      improve medication reconciliation and transitions of care, often involving
      pharmacists. OBJECTIVE: To assess pharmacists' views on their roles in hospital
      based medication reconciliation and discharge counseling and provide their
      recommendations for improving care transitions. METHODS: Eleven study pharmacists
      at 2 hospitals participated in the Pharmacist Intervention for Low Literacy in
      Cardiovascular Disease (PILL-CVD) study and completed semistructured one-on-one
      interviews, which were coded systematically in NVivo. Pharmacists provided their
      perspectives on admission and discharge medication reconciliation, in-hospital
      patient counseling, provision of simple medication adherence aids (eg, pill box,
      illustrated daily medication schedule), and telephone follow-up. RESULTS:
      Pharmacists indicated that they considered medication reconciliation, although
      time consuming, to be their most important role in improving care transitions,
      particularly through detection of errors that required correction in the
      admission medication history. They also identified patients who required
      additional counseling because of poor understanding of their medications.
      Providing adherence aids was felt to be highly valuable for patients with low
      health literacy, although less useful for patients with adequate health literacy.
      Pharmacists noted that having trained administrative staff conduct initial
      postdischarge follow-up calls to screen for issues and triage which patients
      needed pharmacist follow-up was helpful and an efficient use of resources.
      Pharmacists' recommendations for improving care transitions included clear
      communication among team members, protected time for discharge counseling,
      patient and family engagement in discharge counseling, and provision of patient
      education materials. CONCLUSIONS: Pharmacists are well positioned to participate
      in hospital-based medication reconciliation, identify patients with poor
      medication understanding or adherence, and provide tailored patient counseling to
      improve transitions of care. Additional studies are needed to confirm these
      findings in other settings and to determine the efficacy and cost-effectiveness
      of different models of pharmacist involvement.

PMID- 22872753
TI  - Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct
      signatures for nutritional stress.
AB  - Liver steatosis can be induced by fasting or high-fat diet. We investigated by
      lipidomic analysis whether such metabolic states are reflected in the lipidome of
      hepatocyte lipid droplets (LDs) from mice fed normal chow diet (FED), fasted
      (FAS), or fed a high-fat diet (HFD). LC-MS/MS at levels of lipid species profiles
      and of lipid molecular species uncovered a FAS phenotype of LD enriched in
      triacylglycerol (TG) molecular species with very long-chain (VLC)-PUFA residues
      and an HFD phenotype with less unsaturated TG species in addition to
      characteristic lipid marker species. Nutritional stress did not result in
      dramatic structural alterations in diacylglycerol (DG) and phospholipid (PL)
      classes. Moreover, molecular species of bulk TG and of DG indicated concomitant
      de novo TG synthesis and lipase-catalyzed degradation to be active in LDs. DG
      species with VLC-PUFA residues would be preferred precursors for
      phosphatidylcholine (PC) species, the others for TG molecular species. In
      addition, molecular species of PL classes fitted the hepatocyte Kennedy and
      phosphatidylethanolamine methyltransferase pathways. We demonstrate that
      lipidomic analysis of LDs enables phenotyping of nutritional stress. TG species
      are best suited for such phenotyping, whereas structural analysis of TG, DG, and
      PL molecular species provides metabolic insights.

PMID- 22872754
TI  - Protein kinase A modulates the activity of a major human isoform of ABCG1.
AB  - ABCG1 is an ABC half-transporter that exports cholesterol from cells to HDL. This
      study set out to investigate differences in posttranslational processing of two
      human ABCG1 protein isoforms, termed ABCG1(+12) and ABCG1(-12), that differ by
      the presence or absence of a 12 amino acid peptide. ABCG1(+12) is expressed in
      human cells and tissues, but not in mice. We identified two protein kinase A
      (PKA) consensus sites in ABCG1(+12), absent from ABCG1(-12). Inhibition of PKA
      with either of two structurally unrelated inhibitors resulted in a dose-dependent
      increase in cholesterol export from cells expressing ABCG1(+12), whereas ABCG1(
      12)-expressing cells were unaffected. This was associated with stabilization of
      the ABCG1(+12) protein, and ABCG1(+12)-S389 was necessary to mediate these
      effects. Mutation of this serine to aspartic acid, simulating a constitutively
      phosphorylated state, resulted in accelerated degradation of ABCG1(+12) and
      reduced cholesterol export. Engineering an equivalent PKA site into ABCG1(-12)
      rendered this isoform responsive to PKA inhibition, confirming the relevance of
      this sequence. Together, these results demonstrate an additional level of
      complexity to the posttranslational control of this human ABCG1 isoform that is
      absent from ABCG1(-12) and the murine ABCG1 homolog.

PMID- 22872755
TI  - Using gene-network landscape to dissect genotype effects of TCF7L2 genetic
      variant on diabetes and cardiovascular risk.
AB  - The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is,
      to date, the most significant genetic marker associated with Type 2 diabetes
      mellitus (T2DM) risk. Nonetheless, its functional role in disease pathology is
      poorly understood. The aim of the present study was to investigate, in vascular
      smooth muscle cells from 92 patients undergoing aortocoronary bypass surgery, the
      contribution of this SNP in T2DM using expression levels and expression
      correlation comparison approaches, which were visually represented as gene
      interaction networks. Initially, the expression levels of 41 genes (seven TCF7L2
      splice forms and 40 other T2DM relevant genes) were compared between rs7903146
      wild-type (CC) and T2DM-risk (CT + TT) genotype groups. Next, we compared the
      expression correlation patterns of these 41 genes between groups to observe if
      the relationships between genes were different. Five TCF7L2 splice forms and nine
      genes showed significant expression differences between groups. RXRalpha gene was
      pinpointed as showing the most different expression correlation pattern with
      other genes. Therefore, T2DM risk alleles appear to be influencing TCF7L2 splice
      form's expression in vascular smooth muscle cells, and RXRalpha gene is pointed
      out as a treatment target candidate for risk reduction in individuals with high
      risk of developing T2DM, especially individuals harboring TCF7L2 risk genotypes.

PMID- 22872756
TI  - Molecular characterization of the glauce mutant: a central cell-specific function
      is required for double fertilization in Arabidopsis.
AB  - Double fertilization of the egg cell and the central cell by two sperm cells,
      resulting in the formation of the embryo and the endosperm, respectively, is a
      defining characteristic of flowering plants. The Arabidopsis thaliana female
      gametophytic mutant glauce (glc) can exhibit embryo development without any
      endosperm. Here, we show that in glc mutant embryo sacs one sperm cell
      successfully fuses with the egg cell but the second sperm cell fails to fuse with
      the central cell, resulting in single fertilization. Complementation studies
      using genes from the glc deletion interval identified an unusual genomic locus
      having homology to BAHD (for BEAT, AHCT, HCBT, and DAT) acyl-transferases with
      dual transcription units and alternative splicing that could rescue the sterility
      defect of glc. Expression of these transcripts appears restricted to the central
      cell, and expression within the central cell is sufficient to restore fertility.
      We conclude that the central cell actively promotes its own fertilization by the
      sperm cell through a signaling mechanism involving products of At1g65450.
      Successful fertilization of the egg cell is not blocked in the glc mutant,
      suggesting that evolution of double fertilization in flowering plants involved
      acquisition of specific functions by the central cell to enable its role as a
      second female gamete.

PMID- 22872758
TI  - Myostatin inhibits myosatellite cell proliferation and consequently activates
      differentiation: evidence for endocrine-regulated transcript processing.
AB  - Myostatin is a potent negative regulator of muscle growth in mammals. Despite
      high structural conservation, functional conservation in nonmammalian species is
      only assumed. This is particularly true for fish due to the presence of several
      myostatin paralogs: two in most species and four in salmonids (MSTN-1a, -1b, -2a,
      and -2b). Rainbow trout are a rich source of primary myosatellite cells as
      hyperplastic muscle growth occurs even in adult fish. These cells were therefore
      used to determine myostatin's effects on proliferation whereas our earlier
      studies reported its effects on quiescent cells. As in mammals, recombinant
      myostatin suppressed proliferation with no changes in cell morphology. Expression
      of MSTN-1a was several fold higher than the other paralogs and was autoregulated
      by myostatin, which also upregulated the expression of key differentiation
      markers: Myf5, MyoD1, myogenin, and myosin light chain. Thus, myostatin
      stimulated cellular growth inhibition activates rather than represses
      differentiation. IGF-1 stimulated proliferation but had minimal and delayed
      effects on differentiation and its actions were suppressed by myostatin. However,
      IGF-1 upregulated MSTN-2a expression and the processing of its transcript, which
      is normally unprocessed. Myostatin therefore appears to partly mediate IGF
      stimulated myosatellite differentiation in rainbow trout. This also occurs in
      mammals, although the IGF-stimulated processing of MSTN-2a transcripts is highly
      unique and is indicative of subfunctionalization within the gene family. These
      studies also suggest that the myokine's actions, including its antagonistic
      relationship with IGF-1, are conserved and that the salmonid gene family is
      functionally diverging.

PMID- 22872757
TI  - Lysin motif-containing proteins LYP4 and LYP6 play dual roles in peptidoglycan
      and chitin perception in rice innate immunity.
AB  - Plant innate immunity relies on successful detection of microbe-associated
      molecular patterns (MAMPs) of invading microbes via pattern recognition receptors
      (PRRs) at the plant cell surface. Here, we report two homologous rice (Oryza
      sativa) lysin motif-containing proteins, LYP4 and LYP6, as dual functional PRRs
      sensing bacterial peptidoglycan (PGN) and fungal chitin. Live cell imaging and
      microsomal fractionation consistently revealed the plasma membrane localization
      of these proteins in rice cells. Transcription of these two genes could be
      induced rapidly upon exposure to bacterial pathogens or diverse MAMPs. Both
      proteins selectively bound PGN and chitin but not lipopolysaccharide (LPS) in
      vitro. Accordingly, silencing of either LYP specifically impaired PGN- or chitin-
      but not LPS-induced defense responses in rice, including reactive oxygen species
      generation, defense gene activation, and callose deposition, leading to
      compromised resistance against bacterial pathogen Xanthomonas oryzae and fungal
      pathogen Magnaporthe oryzae. Interestingly, pretreatment with excess PGN
      dramatically attenuated the alkalinization response of rice cells to chitin but
      not to flagellin; vice versa, pretreatment with chitin attenuated the response to
      PGN, suggesting that PGN and chitin engage overlapping perception components in
      rice. Collectively, our data support the notion that LYP4 and LYP6 are
      promiscuous PRRs for PGN and chitin in rice innate immunity.

PMID- 22872759
TI  - Enhanced insulin secretion and improved glucose tolerance in mice with homozygous
      inactivation of the Na(+)K(+)2Cl(-) co-transporter 1.
AB  - The intracellular chloride concentration ([Cl(-)](i)) in beta-cells plays an
      important role in glucose-stimulated plasma membrane depolarisation and insulin
      secretion. [Cl(-)](i) is maintained above equilibrium in beta-cells by the action
      of Cl(-) co-transporters of the solute carrier family 12 group A (Slc12a). beta
      Cells express Slc12a1 and Slc12a2, which are known as the bumetanide (BTD)
      sensitive Na(+)-dependent K(+)2Cl(-) co-transporters 2 and 1 respectively. We
      show that mice lacking functional alleles of the Slc12a2 gene exhibit better
      fasting glycaemia, increased insulin secretion in response to glucose, and
      improved glucose tolerance when compared with wild-type (WT). This phenomenon
      correlated with increased sensitivity of beta-cells to glucose in vitro and with
      increased beta-cell mass. Further, administration of low doses of BTD to mice
      deficient in Slc12a2 worsened their glucose tolerance, and low concentrations of
      BTD directly inhibited glucose-stimulated insulin secretion from beta-cells
      deficient in Slc12a2 but expressing intact Slc12a1 genes. Together, our results
      suggest for the first time that the Slc12a2 gene is not necessary for insulin
      secretion and that its absence increases beta-cell secretory capacity. Further,
      impairment of insulin secretion with BTD in vivo and in vitro in islets lacking
      Slc12a2 genes unmasks a potential new role for Slc12a1 in beta-cell physiology.

PMID- 22872760
TI  - Iodothyronine deiodinases: a functional and evolutionary perspective.
AB  - From an evolutionary perspective, deiodinases may be considered pivotal players
      in the emergence and functional diversification of both thyroidal systems (TS)
      and their iodinated messengers. To better understand the evolutionary pathway and
      the concomitant functional diversification of vertebrate deiodinases, in the
      present review we summarized the highlights of the available information
      regarding this ubiquitous enzymatic component that represents the final, common
      physiological link of TS. The information reviewed here suggests that
      deiodination of tyrosine metabolites is an ancient feature of all chordates
      studied to date and consequently, that it precedes the integration of the TS that
      characterize vertebrates. Phylogenetic analysis presented here points to D1 as
      the oldest vertebrate deiodinase and to D2 as the most recent deiodinase gene, a
      hypothesis that agrees with the notion that D2 is the most specialized and finely
      regulated member of the family and plays a key role in vertebrate neurogenesis.
      Thus, deiodinases seem to be major participants in the evolution and functional
      expansion of the complex regulatory network of TS found in vertebrates.

PMID- 22872761
TI  - Regulation of the androgen receptor by post-translational modifications.
AB  - The androgen receptor (AR) is a key molecule in prostate cancer and Kennedy's
      disease. Understanding the regulatory mechanisms of this steroid receptor is
      important in the development of potential therapies for these diseases. One layer
      of AR regulation is provided by post-translational modifications including
      phosphorylation, acetylation, sumoylation, ubiquitination and methylation. While
      these modifications have mostly been studied as individual events, it is becoming
      clear that these modifications can functionally interact with each other in a
      signalling pathway. In this review, the effects of all modifications are
      described with a focus on interplay between them and the functional consequences
      for the AR.

PMID- 22872762
TI  - Pituitary development: a complex, temporal regulated process dependent on
      specific transcriptional factors.
AB  - Pituitary organogenesis is a highly complex and tightly regulated process that
      depends on several transcription factors (TFs), such as PROP1, PIT1 (POU1F1),
      HESX1, LHX3 and LHX4. Normal pituitary development requires the temporally and
      spatially organised expression of TFs and interactions between different TFs, DNA
      and TF co-activators. Mutations in these genes result in different combinations
      of hypopituitarism that can be associated with structural alterations of the
      central nervous system, causing the congenital form of panhypopituitarism. This
      review aims to elucidate the complex process of pituitary organogenesis, to
      clarify the role of the major TFs, and to compile the lessons learned from
      functional studies of TF mutations in panhypopituitarism patients and TF
      deletions or mutations in transgenic animals.

PMID- 22872763
TI  - Expression and effect of fibroblast growth factor 9 in bovine theca cells.
AB  - Fibroblast growth factor 9 (FGF9) protein affects granulosa cell (GC) function
      but is mostly localized to theca cell (TC) and stromal cell of rat ovaries. The
      objectives of this study were to determine the 1) effects of FGF9 on TC
      steroidogenesis, gene expression, and cell proliferation; 2) mechanism of action
      of FGF9 on TCs; and 3) hormonal control of FGF9 mRNA expression in TCs. Bovine
      ovaries were collected from a local slaughterhouse and TCs were collected from
      large (8-22 mm) follicles and treated with various hormones in serum-free medium
      for 24 or 48 h. FGF9 caused a dose-dependent inhibition (P<0.05) of LH- and
      LH+IGF1-induced androstenedione and progesterone production. Also, FGF9 inhibited
      (P<0.05) LH+IGF1-induced expression of LHCGR, CYP11A1, and CYP17A1 mRNA (via real
      time RT-PCR) in TCs. FGF9 had no effect (P>0.10) on STAR mRNA abundance.
      Furthermore, FGF9 inhibited dibutyryl cAMP-induced progesterone and
      androstenedione production in LH+IGF1-treated TCs. By contrast, FGF9 increased
      (P<0.05) the number of bovine TCs. Abundance of FGF9 mRNA in GCs and TCs was
      several-fold greater (P<0.05) in small (1-5 mm) vs large follicles. Tumor
      necrosis factor alpha and WNT5A increased (P<0.05) abundance of FGF9 mRNA in TCs.
      In summary, expression of FGF9 mRNA in TCs is developmentally and hormonally
      regulated. FGF9 may act as an autocrine regulator of ovarian function in cattle
      by slowing TC differentiation via inhibiting LH+IGF1 action via decreasing
      gonadotropin receptors and the cAMP signaling cascade while stimulating
      proliferation of TCs.

PMID- 22872764
TI  - Five things to know about...celiac disease.

PMID- 22872765
TI  - Hookworm folliculitis.

PMID- 22872767
TI  - Prescription drug abuse rising among Aboriginal youths.

PMID- 22872768
TI  - Professionalism: the view from outside medicine.

PMID- 22872769
TI  - The medicine of the prophet.

PMID- 22872771
TI  - Hospital readmission rates under the microscope.

PMID- 22872770
TI  - Systemic corticosteroid monotherapy for clinically diagnosed acute
      rhinosinusitis: a randomized controlled trial.
AB  - BACKGROUND: Patients with acute rhinosinusitis are frequently encountered in
      primary care. Although corticosteroids are being increasingly used for symptom
      control, evidence supporting their use is inconclusive. We conducted a randomized
      controlled trial to examine the effectiveness of systemic corticosteroid
      monotherapy for clinically diagnosed, uncomplicated acute rhinosinusitis.
      METHODS: We conducted a block-randomized, double-blind, placebo-controlled
      clinical trial at 54 primary care practices (68 family physicians) in the
      Netherlands between Dec. 30, 2008, and Apr. 28, 2011. Adult patients with
      clinically diagnosed acute rhinosinusitis were randomly assigned to receive
      either prednisolone 30 mg/d or placebo for 7 days and asked to complete a symptom
      diary for 14 days. The primary outcome measure was the proportion of patients
      with resolution of facial pain or pressure on day 7. RESULTS: Of the 185 patients
      included in the trial (93 in the treatment group, 92 in the placebo group), 2
      withdrew from the study and 9 were excluded from the primary analysis because of
      incomplete symptom reporting. The remaining 174 patients (88 in the treatment
      group, 86 in the placebo group) were included in the intention-to-treat analysis.
      The proportions of patients with resolution of facial pain or pressure on day 7
      were 62.5% (55/88) in the prednisolone group and 55.8% (48/86) in the placebo
      group (absolute risk difference 6.7%, 95% confidence interval -7.9% to 21.2%).
      The groups were similar with regard to the decrease over time in the proportion
      of patients with total symptoms (combined symptoms of runny nose, postnasal
      discharge, nasal congestion, cough and facial pain) and health-related quality of
      life. Adverse events were mild and did not differ significantly between the
      groups. INTERPRETATION: Systemic corticosteroid monotherapy had no clinically
      relevant beneficial effects among patients with clinically diagnosed acute
      rhinosinusitis. Netherlands Trial Register registration no. 1295
      (www.trialregister.nl/trialreg/index.asp).

PMID- 22872773
TI  - Ileocecal ulceration and granulomatous ileitis as an unusual presentation of
      typhoid fever.

PMID- 22872774
TI  - Plastid proteostasis and heterologous protein accumulation in transplastomic
      plants.

PMID- 22872776
TI  - Dependence of subjective image focus on the magnitude and pattern of high order
      aberrations.
AB  - The  image formed by the eye's optics is inherently blurred by aberrations
      specific to the individual's eyes. We examined to what extent judgments of
      perceived focus depend on the total magnitude as opposed to the specific pattern
      of blur introduced by the eye's high order aberrations (HOA). An Adaptive Optics
      system was used to simultaneously correct each subject's wave aberrations and
      display natural images blurred by simulated aberrations. To isolate the effects
      of blur magnitude, images were blurred by pure symmetric defocus, and subjects
      judged the level of the defocus that subjectively appeared best focused (i.e.,
      neither too blurred nor too sharp). These settings were strongly correlated with
      the native blur magnitude. To isolate the effect of the HOA pattern, retinal
      image blur was instead maintained at a constant blur (Strehl Ratio) equal to each
      subject's natural blur, and subjects judged the best-focused image from pairs of
      images blurred by different patterns of HOA, one selected from 100 patterns, the
      other blurred by a reference pattern which included the subject's natural HOA,
      rotated HOA, or nine other HOA patterns. The percentage of images judged as best
      focused was not systematically higher when filtered with the subject's own HOA
      pattern. However, all subjects preferred their own HOA to the rotated version
      significantly more often (57% versus 45% on average across subjects). The
      representation of subjective image focus thus appears to be driven primarily by
      the overall amount of blur and only weakly by HOA blur orientation.

PMID- 22872775
TI  - Stem transcriptome reveals mechanisms to reduce the energetic cost of shade
      avoidance responses in tomato.
AB  - While the most conspicuous response to low red/far-red ratios (R:FR) of shade
      light perceived by phytochrome is the promotion of stem growth, additional, less
      obvious effects may be discovered by studying changes in the stem transcriptome.
      Here, we report rapid and reversible stem transcriptome responses to R:FR in
      tomato (Solanum lycopersicum). As expected, low R:FR promoted the expression of
      growth-related genes, including those involved in the metabolism of cell wall
      carbohydrates and in auxin responses. In addition, genes involved in flavonoid
      synthesis, isoprenoid metabolism, and photosynthesis (dark reactions) were
      overrepresented in clusters showing reduced expression in the stem of low R:FR
      treated plants. Consistent with these responses, low R:FR decreased the levels of
      flavonoids (anthocyanin, quercetin, kaempferol) and selected isoprenoid
      derivatives (chlorophyll, carotenoids) in the stem and severely reduced the
      photosynthetic capacity of this organ. However, lignin contents were unaffected.
      Low R:FR reduced the stem levels of jasmonate, which is a known inducer of
      flavonoid synthesis. The rate of stem respiration was also reduced in low R:FR
      treated plants, indicating that by downsizing the stem photosynthetic apparatus
      and the levels of photoprotective pigments under low R:FR, tomato plants reduce
      the energetic cost of shade-avoidance responses.

PMID- 22872777
TI  - Auditory transients do not affect visual sensitivity in discriminating between
      objective streaming and bouncing events.
AB  - With  few exceptions, the sound-induced bias toward bouncing characteristic of
      the stream/bounce effect has been demonstrated via subjective responses, leaving
      open the question whether perceptual factors, decisional factors, or some
      combination of the two underlie the illusion. We addressed this issue directly,
      using a novel stimulus and signal detection theory to independently characterize
      observers' sensitivity (d') and criterion (c) when discriminating between
      objective streaming and bouncing events in the presence or absence of a brief
      sound at the point of coincidence. We first confirmed that sound-induced motion
      reversals persist despite rendering the targets visually distinguishable by
      differences in texture density. Sound-induced bouncing persisted for targets
      differing by as many as nine just-noticeable-differences (JNDs).  We then
      exploited this finding in our signal detection paradigm in which observers
      discriminated between objective streaming and bouncing events. We failed to find
      any difference in sensitivity (d') between sound and no-sound conditions, but we
      did observe a significantly more liberal criterion (c) in the sound condition
      than the no-sound condition. The results suggest that the auditory-induced bias
      toward bouncing in this context is attributable to a sound-induced shift in
      criterion implicating decisional processes rather than perceptual processes
      determining responses to these displays.

PMID- 22872778
TI  - Efficacy of intraoperative radiotherapy targeted to the abdominal lymph node area
      in patients with esophageal carcinoma.
AB  - We investigated whether intraoperative radiotherapy (IORT) during curative
      surgery for esophageal carcinoma is useful or not. The cases of 117 patients
      diagnosed with thoracoabdominal esophageal carcinoma who underwent curative
      surgery between 1986 and 2007 were reviewed: 72 patients received IORT (IORT
      group) and 45 did not (non-IORT group). Upper abdominal lymphadenectomy was
      performed in 115 patients (98.5%). Seventy patients (59.8%) received chemotherapy
      and 80 patients (68.4%) received external radiotherapy. IORT encompassed the
      upper abdominal lymph node area. A single-fraction dose of 20-30 Gy was delivered
      using high-energy electrons. Median follow-up duration for patients was 7.4
      years. The 5-year overall survival rate did not significantly differ between the
      IORT and non-IORT groups. However, the 5-year abdominal control rate was
      significantly higher in the IORT group (89.2%) than in the non-IORT group (72.9%;
      P = 0.022). We next focused on a patient subgroup with a primary lesion in the
      lower thoracic or abdominal esophagus or measuring >6 cm in length since this
      subgroup is probably at high risk of upper abdominal lymph node metastasis. Of
      the 117 patients, 75 belonged to this subgroup, and among them 45 received IORT.
      Both univariate and multivariate analysis revealed the survival rate was
      significantly higher in patients who received IORT than in those who did not (P =
      0.033 univariate; 0.026 multivariate). There were no obvious perioperative
      complications solely attributed to IORT. IORT for esophageal carcinoma will
      likely be effective for patients with a primary lesion in the lower thoracic or
      abdominal esophagus, or with a long lesion.

PMID- 22872780
TI  - Antisense transcription is pervasive but rarely conserved in enteric bacteria.
AB  - Noncoding RNAs, including antisense RNAs (asRNAs) that originate from the
      complementary strand of protein-coding genes, are involved in the regulation of
      gene expression in all domains of life. Recent application of deep-sequencing
      technologies has revealed that the transcription of asRNAs occurs genome-wide in
      bacteria. Although the role of the vast majority of asRNAs remains unknown, it is
      often assumed that their presence implies important regulatory functions, similar
      to those of other noncoding RNAs. Alternatively, many antisense transcripts may
      be produced by chance transcription events from promoter-like sequences that
      result from the degenerate nature of bacterial transcription factor binding
      sites. To investigate the biological relevance of antisense transcripts, we
      compared genome-wide patterns of asRNA expression in closely related enteric
      bacteria, Escherichia coli and Salmonella enterica serovar Typhimurium, by
      performing strand-specific transcriptome sequencing. Although antisense
      transcripts are abundant in both species, less than 3% of asRNAs are expressed at
      high levels in both species, and only about 14% appear to be conserved among
      species. And unlike the promoters of protein-coding genes, asRNA promoters show
      no evidence of sequence conservation between, or even within, species. Our
      findings suggest that many or even most bacterial asRNAs are nonadaptive by
      products of the cell's transcription machinery. IMPORTANCE Application of high
      throughput methods has revealed the expression throughout bacterial genomes of
      transcripts encoded on the strand complementary to protein-coding genes. Because
      transcription is costly, it is usually assumed that these transcripts, termed
      antisense RNAs (asRNAs), serve some function; however, the role of most asRNAs is
      unclear, raising questions about their relevance in cellular processes. Because
      natural selection conserves functional elements, comparisons between related
      species provide a method for assessing functionality genome-wide. Applying such
      an approach, we assayed all transcripts in two closely related bacteria,
      Escherichia coli and Salmonella enterica serovar Typhimurium, and demonstrate
      that, although the levels of genome-wide antisense transcription are similarly
      high in both bacteria, only a small fraction of asRNAs are shared across species.
      Moreover, the promoters associated with asRNAs show no evidence of sequence
      conservation between, or even within, species. These findings indicate that
      despite the genome-wide transcription of asRNAs, many of these transcripts are
      likely nonfunctional.

PMID- 22872779
TI  - Does ionizing radiation influence Alzheimer's disease risk?
AB  - Alzheimer's disease (AD) is a human neurodegenerative disease, and its global
      prevalence is predicted to increase dramatically in the following decades. There
      is mounting evidence describing the effects of ionizing radiation (IR) on the
      brain, suggesting that exposure to IR might ultimately favor the development of
      AD. Therefore better understanding the possible connections between exposure to
      IR and AD pathogenesis is of utmost importance. In this review, recent
      developments in the research on the biological and cognitive effects of IR in the
      brain will be explored. Because AD is largely an age-related pathology, the
      effects of IR on ageing will be investigated.

PMID- 22872781
TI  - Sustained H(2) production driven by photosynthetic water splitting in a
      unicellular cyanobacterium.
AB  - The relationship between dinitrogenase-driven H(2) production and oxygenic
      photosynthesis was investigated in a unicellular cyanobacterium, Cyanothece sp.
      ATCC 51142, using a novel custom-built photobioreactor equipped with advanced
      process control. Continuously illuminated nitrogen-deprived cells evolved H(2) at
      rates up to 400 umol ? mg Chl(-1) ? h(-1) in parallel with uninterrupted
      photosynthetic O(2) production. Notably, sustained coproduction of H(2) and O(2)
      occurred over 100 h in the presence of CO(2), with both gases displaying inverse
      oscillations which eventually dampened toward stable rates of 125 and 90 umol ?
      mg Chl(-1) ? h(-1), respectively. Oscillations were not observed when CO(2) was
      omitted, and instead H(2) and O(2) evolution rates were positively correlated.
      The sustainability of the process was further supported by stable chlorophyll
      content, maintenance of baseline protein and carbohydrate levels, and an enhanced
      capacity for linear electron transport as measured by chlorophyll fluorescence
      throughout the experiment. In situ light saturation analyses of H(2) production
      displayed a strong dose dependence and lack of O(2) inhibition. Inactivation of
      photosystem II had substantial long-term effects but did not affect short-term
      H(2) production, indicating that the process is also supported by photosystem I
      activity and oxidation of endogenous glycogen. However, mass balance calculations
      suggest that carbohydrate consumption in the light may, at best, account for no
      more than 50% of the reductant required for the corresponding H(2) production
      over that period. Collectively, our results demonstrate that uninterrupted H(2)
      production in unicellular cyanobacteria can be fueled by water photolysis without
      the detrimental effects of O(2) and have important implications for sustainable
      production of biofuels. IMPORTANCE: The study provides an important insight into
      the photophysiology of light-driven H(2) production by the nitrogen-fixing
      cyanobacterium Cyanothece sp. strain ATCC 51142. This work is also of
      significance for biotechnology, supporting the feasibility of "direct
      biophotolysis." The sustainability of the process, highlighted by prolonged gas
      evolution with no clear sign of significant decay or apparent photodamage,
      provides a foundation for the future development of an effective, renewable, and
      economically efficient bio-H(2) production process.

PMID- 22872783
TI  - Training and Consultation in Evidence-Based Psychosocial Treatments in Public
      Mental Health Settings: The ACCESS Model.
AB  - We present a model of training in evidence-based psychosocial treatments (EBTs).
      The ACCESS (assess and adapt, convey basics, consult, evaluate, study outcomes,
      sustain) model integrates principles and findings from adult education and
      training literatures, research, and practical suggestions based on a community
      based clinician training program. Descriptions of the steps are provided as a
      means of guiding implementation efforts and facilitating training partnerships
      between public mental health agencies and practitioners of EBTs.

PMID- 22872784
TI  - Real-Time, Label-Free, All-Electrical Detection of Salmonella typhimurium Using
      Lead Zirconate Titanate/Gold-Coated Glass Cantilevers at any Relative Humidity.
AB  - We have examined non-insulated PZT/gold-coated glass cantilevers for real-time,
      label-free detection of Salmonella t. by partial dipping at any relative
      humidity. The PZT/gold-coated glass cantilevers were consisted of a 0.127 mm
      thick PZT layer about 0.8 mm long, 2 mm wide bonded to a 0.15 mm thick gold
      coated glass layer with a 3.0 mm long gold-coated glass tip for detection. We
      showed that by placing the water level at the nodal point, about 0.8 mm from the
      free end of the gold-glass tip, there was a 1-hr window in which the resonance
      frequency was stable despite the water level change by evaporation at 20%
      relative humidity or higher. By dipping the cantilevers to their nodal point, we
      were able to do real-time, label-free detection without background resonance
      frequency corrections at any relative humidity. The partially dipped PZT/gold
      coated glass cantilever exhibited mass detection sensitivity, Deltam/Deltaf = 
      5*10(-11)g/Hz, and a detection concentration sensitivity, 5*10(3) cells/ml in 2
      ml of liquid, which was about two orders of magnitude lower than that of a 5 MHz
      QCM. It was also about two orders of magnitude lower than the infection dosage
      and one order of magnitude lower that the detection limit of a commercial Raptor
      sensor.

PMID- 22872782
TI  - Respiratory syncytial virus fusion protein-induced toll-like receptor 4 (TLR4)
      signaling is inhibited by the TLR4 antagonists Rhodobacter sphaeroides
      lipopolysaccharide and eritoran (E5564) and requires direct interaction with MD
      2.
AB  - Respiratory syncytial virus (RSV) is a leading cause of infant mortality
      worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally
      diverse microbe-associated molecular patterns, is activated by the RSV fusion (F)
      protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner.
      TLR4 signaling by LPS also requires the presence of an additional protein, MD-2.
      Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as
      well, although this hypothesis has not been formally tested. LPS-free RSV F
      protein was found to activate NF-kappaB in HEK293T transfectants that express
      wild-type (WT) TLR4 and CD14, but only when MD-2 was coexpressed. These findings
      were confirmed by measuring F-protein-induced interleukin 1beta (IL-1beta) mRNA
      in WT versus MD-2(-/-) macrophages, where MD-2(-/-) macrophages failed to show IL
      1beta expression upon F-protein treatment, in contrast to the WT. Both
      Rhodobacter sphaeroides LPS and synthetic E5564 (eritoran), LPS antagonists that
      inhibit TLR4 signaling by binding a hydrophobic pocket in MD-2, significantly
      reduced RSV F-protein-mediated TLR4 activity in HEK293T-TLR4-CD14-MD-2
      transfectants in a dose-dependent manner, while TLR4-independent NF-kappaB
      activation by tumor necrosis factor alpha (TNF-alpha) was unaffected. In vitro
      coimmunoprecipitation studies confirmed a physical interaction between native RSV
      F protein and MD-2. Further, we demonstrated that the N-terminal domain of the F1
      segment of RSV F protein interacts with MD-2. These data provide new insights
      into the importance of MD-2 in RSV F-protein-mediated TLR4 activation. Thus,
      targeting the interaction between MD-2 and RSV F protein may potentially lead to
      novel therapeutic approaches to help control RSV-induced inflammation and
      pathology. IMPORTANCE: This study shows for the first time that the fusion (F)
      protein of respiratory syncytial virus (RSV), a major cause of bronchiolitis and
      death, particularly in infants and young children, physically interacts with the
      Toll-like receptor 4 (TLR4) coreceptor, MD-2, through its N-terminal domain. We
      show that F protein-induced TLR4 activation can be blocked by lipid A analog
      antagonists. This observation provides a strong experimental rationale for
      testing such antagonists in animal models of RSV infection for potential use in
      people.

PMID- 22872785
TI  - TNBCtype: A Subtyping Tool for Triple-Negative Breast Cancer.
AB  - MOTIVATION: Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer
      group, and identification of molecular subtypes is essential for understanding
      the biological characteristics and clinical behaviors of TNBC as well as for
      developing personalized treatments. Based on 3,247 gene expression profiles from
      21 breast cancer data sets, we discovered six TNBC subtypes from 587 TNBC samples
      with unique gene expression patterns and ontologies. Cell line models
      representing each of the TNBC subtypes also displayed different sensitivities to
      targeted therapeutic agents. Classification of TNBC into subtypes will advance
      further genomic research and clinical applications. RESULT: We developed a web
      based subtyping tool TNBCtype for candidate TNBC samples using our gene
      expression meta data and classification methods. Given a gene expression data
      matrix, this tool will display for each candidate sample the predicted subtype,
      the corresponding correlation coefficient, and the permutation P-value. We offer
      a user-friendly web interface to predict the subtypes for new TNBC samples that
      may facilitate diagnostics, biomarker selection, drug discovery, and the more
      tailored treatment of breast cancer.

PMID- 22872787
TI  - Identification of breast cancer-associated lipids in scalp hair.
AB  - A correlation between the presence of breast cancer and a change in the
      synchrotron-generated X-ray diffraction (XRD) pattern of hair has been reported
      in several publications by different groups, and on average XRD-based assays
      detect around 75% of breast cancer patients in blinded studies. To date, the
      molecular mechanisms leading to this alteration are largely unknown. We have
      determined that the alteration is likely to be due to the presence of one or more
      breast cancer-associated phospholipids. Further characterization of these lipids
      could be used to develop a novel, sensitive and specific screening test for
      breast cancer, based on hair initially, and potentially extendable to other
      biological samples.

PMID- 22872788
TI  - Radiation-Triggered NF-kappaB Activation is Responsible for the Angiogenic
      Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and
      Growth.
AB  - Tumors require blood supply to survive, grow, and metastasize. This involves the
      process of angiogenesis signaling for new blood vessel growth into a growing
      tumor mass. Understanding the mechanism of the angiogenic signaling pathway and
      neovascularization for breast cancer cell proliferation and growth would help to
      develop molecular interventions and achieve disease free survival. Our hypothesis
      is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic
      signaling pathway in the neighboring endothelial cells resulting in
      neovascularization for breast cancer cell growth. The angiogenic signaling
      pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of
      a transcriptional regulator NF-kappaB, which in turn is triggered by therapeutic
      doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were
      exposed to Cesium-137 ((137)Cs) gamma rays to a total dose of 2 Gy at a dose rate
      of 1.03 Gy/min. The results of mobility shift assay showed that radiation at
      clinical doses (2 Gy) could induce NF-kappaB DNA-binding activity. Then, we
      examined the communication of angiogenic signals from irradiated MCF-7 cells to
      vascular endothelial cells. At the protein level, the western blot showed
      induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2
      Gy. Inhibition of NF-kappaB activation attenuated VEGF and FGF-2 levels. These
      factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra
      cellular medium were both increased, after 2 Gy exposures. We also observed
      corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells
      that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro
      tube formation assays provided evidence that irradiated MCF-7 cells transmit
      signals to potentiate cultured non-irradiated endothelial cells to form tube
      networks, which is the hallmark of neovascularization. Inhibition of NF-kappaB
      activation attenuated irradiated MCF-7-induced tube network formation. The data
      provide evidence that the radiation exposure is responsible for tumor growth and
      maintenance by inducing an angiogenic signaling pathway through activation of NF
      kappaB.

PMID- 22872786
TI  - Molecular serum markers of liver fibrosis.
AB  - Fibrosis is a hallmark histologic event of chronic liver diseases and is
      characterized by the excessive accumulation and reorganization of the
      extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver
      biopsy. As this procedure has various limitations, including risk of patient
      injury and sampling error, a non-invasive serum marker for liver fibrosis is
      desirable. The increasing understanding of the pathogenesis of hepatic fibrosis
      has suggested several markers which could be useful indicators of hepatic
      fibrogenesis and fibrosis. These markers include serum markers of liver function,
      ECM synthesis, fibrolytic processes, ECM degradation and fibrogenesis related
      cytokines. Recently, neo-epitopes, which are post-translational modifications of
      proteins, have been successfully used in bone and cartilage diseases which are
      characterized by extensive ECM remodeling. Increasing numbers of studies are
      being undertaken to identify neo-epitopes generated during liver fibrosis, and
      which ultimately might be useful for diagnosing and monitoring fibrogenesis. To
      date, the metalloproteinases generated fragment of collagen I, III, IV and VI
      have been proven to be elevated in two rat models of fibrosis. This review
      summarizes the recent efforts that have been made to identify potentially
      reliable non-invasive serum markers. We used the recently proposed BIPED (Burden
      of disease, Investigative, Prognostic, Efficacy and Diagnostic) system to
      characterize potential serum markers and neo-epitope markers that have been
      identified to date.

PMID- 22872789
TI  - Human Streptococcus suis Endocarditis: Echocardiographic Features and Clinical
      Outcome.
AB  - BACKGROUND: Human Streptococcus suis endocarditis occurs infrequently and
      continues to be a serious illness with high mortality. However, knowledge of the
      echocardiographic features and clinical outcome of this disease remains unclear.
      METHODS: One hundred and fourteen patients were identified in a prospective
      study, and hospitalized at Queen Sirikit Heart Center and Srinagarind Hospital,
      Khon Kaen University. Echocardiography was routinely performed in all patients.
      RESULTS: Between January 2010 and December 2011, three cases of S. suis
      endocarditis were diagnosed. All cases were male and aged 27-53 years. The most
      common risk factor for contracting S. suis infection was eating undercooked pork.
      Three patients presented with congestive heart failure. Transthoracic
      echocardiography demonstrated large, highly mobile vegetations and severe
      valvular damage. Aortic valve involvement was documented in two patients, and
      mitral valve involvement in one. One patient presented with embolic stroke and
      one with arterial occlusion. All patients underwent urgent valve replacement with
      a good clinical outcome. CONCLUSION: The echocardiographic features of S. suis
      endocarditis show destructive, extensive valvular damage and early embolization
      with a fulminant course, needing early surgical intervention with a good clinical
      outcome.

PMID- 22872790
TI  - Clinical utility of treprostinil and its overall place in the treatment of
      pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a disease that leads to characteristic
      vascular wall remodeling and hemodynamic alterations. Consequently, this
      pulmonary vascular disease contributes to substantial morbidity and mortality in
      afflicted patients. PAH may be idiopathic in nature or associated with connective
      tissue disease, chronic liver disease, human immunodeficiency virus, congenital
      heart disease, and a growing list of other conditions. There are currently nine
      Food and Drug Administration-approved therapies for specific PAH treatment.
      Therapeutic targets include prostacyclin replacement, endothelin-1 antagonism,
      and phosphodiesterase-5 inhibition. This article focuses on the prostanoid
      treprostinil and explores its role in the management of patients with PAH.

PMID- 22872791
TI  - Relating the construction and maintenance of maternal ill-health in rural
      Indonesia.
AB  - Estimates suggest that over 350,000 deaths and more than 20 million severe
      disabilities result from the complications of pregnancy, childbirth or its
      management each year. Death and disability occur predominately among
      disadvantaged women in resource-poor settings and are largely preventable with
      adequate delivery care. This paper presents the substantive findings and policy
      implications from a programme of PhD research, of which the overarching objective
      was to assess quality of, and access to, care in obstetric emergencies. Three
      critical incident audits were conducted in two rural districts on Java,
      Indonesia: a confidential enquiry, a verbal autopsy survey, and a community-based
      review. The studies examined cases of maternal mortality and severe morbidity
      from the perspectives of local service users and health providers. A range of
      inter-related determining factors was identified. When unexpected delivery
      complications occurred, women and families were often uninformed, unprepared,
      found care unavailable, unaffordable, and many relied on traditional providers.
      Midwives in villages made important contributions by stabilising women and
      facilitating referrals but were often scarce in remote areas and lacked
      sufficient clinical competencies and payment incentives to treat the poor.
      Emergency transport was often unavailable and private transport was unreliable
      and incurred costs. In facilities, there was a reluctance to admit poorer women
      and those accepted were often admitted to ill-equipped, under-staffed wards. As a
      result, referrals between hospitals were also common. Otherwise, social health
      insurance, designed to reduce financial barriers, was particularly problematic,
      constraining quality and access within and outside facilities. Health workers and
      service users provided rich and explicit assessments of care and outcomes. These
      were used to develop a conceptual model in which quality and access are conceived
      of as social processes, observable through experience and reflective of the
      broader relationships between individuals and health systems. According to this
      model, differential quality and access can become both socially legitimate
      (imposed by structural arrangements) and socially legitimised (reciprocally
      maintained through the actions of individuals). This interpretation suggests that
      in a context of commodified care provision, adverse obstetric outcomes will occur
      and recur for disadvantaged women. Health system reform should focus on the
      unintended effects of market-based service provision to exclude those without the
      ability to pay for delivery care directly.

PMID- 22872792
TI  - Fertility Preservation Methods in Breast Cancer.
AB  - Thanks to the recent advances in reproductive medicine, more and more young women
      with breast cancer may be offered the possibility of preserving their fertility.
      Fertility can be endangered by chemotherapy, by treatment duration and by
      patient's age at diagnosis. The currently available means to preserve a young
      woman's fertility are pharmacological protection with gonadotrophin-releasing
      hormone analogues during chemotherapy, and ovarian tissue or oocyte/embryo
      freezing before treatment. New future venues, including in vitro maturation, will
      improve the feasibility and efficacy of the fertility preservation methods in
      breast cancer patients.

PMID- 22872793
TI  - Being Pregnant and Diagnosed with Breast Cancer.
AB  - Breast cancer during pregnancy (BCP) is an important subgroup within the young
      and very young breast cancer patients. It accounts for about 1% of all breast
      cancers. Due to an increased awareness, the attitude towards breast cancer during
      pregnancy has changed and, today, women with BCP are more likely to receive
      standard chemotherapy and have a term delivery instead of being advised to
      interrupt the pregnancy or undergo an early preterm delivery. This increased
      knowledge is based on small cohort studies and international collaborations such
      as the registry by the German Breast Group for BCP and the initiative of the
      European Society of Gynaecological Oncology (ESGO). Guidelines and
      recommendations such as the German guidelines by the AGO (Arbeitsgemeinschaft
      Gynakologische Onkologie, www.ago-online.org) and the National Comprehensive
      Cancer Network (NCCN) guidelines include recommendations for BCP. In general,
      surgery and chemotherapy (beyond the 13th week of gestation) can be safely
      performed during pregnancy. Chemotherapy should follow the treatment
      recommendations for breast cancer in young women. Trastuzumab, endocrine
      treatment, and radiotherapy are not indicated during pregnancy. Preterm delivery
      should be avoided as far as possible because it bears a higher risk of infant
      morbidity and mortality. The treatment of BCP should be planned within a
      multidisciplinary team including perinatologists, obstetricians and
      neonatologists.

PMID- 22872794
TI  - Pregnancy after Breast Cancer: Myths and Facts.
AB  - Most young breast cancer survivors consider reproductive issues to be of great
      importance, but many questions remain undervalued and unanswered. Overall,
      available data support the safety and feasibility of pregnancy and breastfeeding
      after breast cancer. The accuracy of the evidence is however limited by: i) the
      retrospective and frequently incomplete population-based nature of the data, ii)
      data not representing the entire population, iii) patient-related effects, iv)
      underpowered sample size, and v) lack of control for biological factors and risk
      determinants. We review the available evidence in light of these limitations
      which outline the need for prospective data collection and focused priority
      research.

PMID- 22872795
TI  - Clinical Implications of Micrometastasis Detection in Internal Mammary Nodes of
      Breast Cancer Patients.
AB  - BACKGROUND: The aim of this study was to assess the efficiency of step-serial
      sectioning (SSS) combined with hematoxylin and eosin (H&E) and
      immunohistochemical (IHC) staining in detecting micrometastasis of internal
      mammary lymph nodes (IMLNs).  PATIENTS AND METHODS: 135 IMLNs from 88 breast
      cancer patients were re-examined by SSS, combined with either H&E or IHC staining
      of the biomarkers cytokeratin-19 and epithelial membrane antigen.  RESULTS: Of
      the 135 IMLNs, 6 nodes from 5 cases displayed 1 or more micrometastases.
      Histological grade and lymphovascular invasion status were significantly
      correlated with micrometastasis in the IMLNs (p = 0.018 and 0.001, respectively).
      Of the 6 nodes positive for micrometastasis, 1 node was detected by both H&E and
      IHC staining. The remaining 5 nodes from 4 cases showed evident tumor cells only
      by IHC staining. Finally 8 of the 83 patients (9.64%) without IMLN metastasis
      showed distant metastasis, while 2 of the 5 patients (40%) with IMLN metastasis
      showed distant metastasis within 28 months of operation.  CONCLUSION: SSS
      combined with H&E and IHC staining is more efficient in detecting micrometastasis
      than classic routine single-slice H&E only.

PMID- 22872796
TI  - Evaluation of the Effects of Chitosan Hemostasis Dressings on Hemorrhage Caused
      by Breast Biopsy.
AB  - BACKGROUND: Female breast tissue has a rich vascular supply and carries a high
      risk of excessive bleeding during large-core needle biopsy. It is crucial to
      shorten bleeding time and reduce hematoma size after the procedure. Currently,
      more efficient hemostatic dressings are becoming available.  MATERIAL AND
      METHODS: The bleeding time and hematoma size after breast biopsy with use of
      either Instant Clot Pad (ICP) dressings or cotton gauze were compared.  RESULTS:
      ICP could attract a vast number of red blood cells and formed blood clots in
      about 30 s (in vitro blood clotting test). In clinical breast biopsy
      examinations, the average bleeding time with ICP was significantly reduced to
      about 2.9 min as compared to 6.4 min with cotton gauze (p < 0.005). The average
      hematoma size was also reduced with the use of ICP (0.89 cm(3)) as compared to
      cotton gauze (1.28 cm(3)). In patients with benign breast disease, ICP
      significantly reduced hematoma size.  CONCLUSION: ICP used after breast biopsy
      could shorten the bleeding time in all patients, and significantly reduce the
      hematoma size in patients with benign compared to those with malignant breast
      disease.

PMID- 22872797
TI  - Management of Patients with Granulomatous Mastitis: Analysis of 31 Cases.
AB  - BACKGROUND: Granulomatous mastitis is a benign recurrent disease. Accurate
      diagnosis is only by histopathology.  PATIENTS AND METHODS: 31 cases with
      histological diagnosis were retrospectively analyzed.  RESULTS: Mean follow-up
      was 42.4 months for recurrent and 27.8 months for non-recurrent cases. Etiology
      was tuberculosis in 1 case. 5 cases (16%) relapsed. 6 patients (19.3%) treated
      with abscess drainage healed completely, but 50% relapsed. Relapses were treated
      with excision or steroids. Steroid therapy was the initial treatment in 12 cases
      (38.7%), with 1 relapse (8.3%) which was treated in the same manner. 2 patients
      had incomplete response necessitating excision, and another 2 developed abscesses
      which were treated with steroids or excision after drainage. Surgical excision
      was preferred in 12 cases (38.7%) due to suspicion for carcinoma in 8 patients
      (25.8%) and/or low probability of poor cosmetic outcome. All healed without
      complication, and recurrence was observed in 1 case (8.3%) which was treated with
      re-excision.  CONCLUSION: Both excision and steroid therapy had low and similar
      relapse rates, but excision was superior to steroid therapy in providing strict
      diagnosis with much faster healing and fewer complications. In refractory cases,
      and when deformity is inevitable, steroid therapy should be preferred.

PMID- 22872798
TI  - Axillary Padding without Drainage after Axillary Lymphadenectomy - a Prospective
      Study of 299 Patients with Early Breast Cancer.
AB  - BACKGROUND: After lymphadenectomy for early breast cancer, seroma formation is a
      constant event requiring a suction drainage. This drainage is the strongest
      obstacle to reducing the hospital stay. Axillary padding without drainage appears
      to be a valuable option amid the various solutions for reducing the hospital
      stay.  METHODS: We conducted a comparison between 114 patients with padding and
      185 patients with drainage. Data were obtained from 2 successive prospective
      studies.  RESULTS: The mean hospital stay was 2.4 days (range 1-4) in the padding
      group and 4.2 days (range 2-9) in the drainage group (p < 0.05). There were fewer
      needle aspirations for seroma in the padding group (8.8 vs. 23%, p < 0.05). At 6
      weeks, only 28% (32/114) of the patients in the padding group reported pain
      versus 51% (94/185) in the drainage group. The mean pain intensity at 6 weeks was
      3 and 4.3 respectively (p < 0.0001).  CONCLUSION: Axillary padding without
      drainage was associated with a better post-operative course than suction drainage
      in this historical comparison, and the hospital stay was significantly shortened.
      There are only few series published on this new technique but they all indicate
      good feasibility and good tolerance. A large randomised multicentric evaluation
      is now warranted.

PMID- 22872799
TI  - Detected, yet not Diagnosed - Breast Cancer Screening with MRI Mammography in
      High-Risk Women.
AB  - BACKGROUND: MRI has been demonstrated to be the most sensitive imaging method for
      detecting breast cancer in women at high risk, allowing depiction of cancers that
      are occult on mammography, ultrasound and clinical breast examination. This high
      sensitivity is tempered by imperfect specificity due to overlap in the features
      of benign and malignant lesions.  CASE: We present the case of a young BRCA2
      mutation carrier whose breast cancer could have been diagnosed 2 years earlier;
      this is a rare case of a false-negative finding in MRI.  DISCUSSION: We discuss
      morphological, physiological and psychological reasons for underestimation of MRI
      sets, especially in young women.  CONCLUSION: We conclude that double reading in
      MR screening for breast cancer in high-risk women, as conducted for mammography
      screening, could be considered.

PMID- 22872800
TI  - Recurrent Mastitis after Core Needle Biopsy: Case Report of an Unusual
      Complication after Core Needle Biopsy of a Phyllodes Tumor.
AB  - BACKGROUND: In the routine work-up of suspect breast lesions, ultrasound
      controlled core needle biopsy (CNB) is the most common tool to acquire tissue for
      histopathologic analysis in a safe, quick and convenient way. Complications are
      generally rare. The most common complications are hematoma and infection, each
      with less than 1 in 1000 cases.  CASE REPORT: Here, we present a case of a 48
      year-old patient who underwent CNB for several lesions that were assessed as
      Breast Imaging Report and Data System (BI-RADS) IV in breast ultrasound and
      mammography. In the past, she had had 2 bilateral breast reduction surgeries and
      1 open biopsy of a fibroadenoma. Histology revealed a phyllodes tumor. Following
      this, mastitis occurred which was resistant to common conservative measurements
      such as intravenous antibiotics over months. Finally, mastectomy was performed,
      followed by adequate wound healing.  CONCLUSIONS: In the presented case, the
      prolonged course of breast infection after CNB was not as expected. If this
      occurs, conservative treatment with antibiotics can be initiated. Possible
      additional risk factors such as diabetes mellitus, steroid therapy, or
      immunosuppression should be identified. However, in case of missing recovery,
      wide surgical excision is recommended.

PMID- 22872801
TI  - Inactivation of the tick-borne encephalitis virus by RNA-cleaving compounds.
AB  - The tick-borne encephalitis virus (TBEV) is an RNA-containing enveloped virus,
      which poses a major threat to the well-being and health of humans. In this study,
      we describe an approach to the inactivation of TBEV, which involves the
      degradation of viral RNA by artificial ribonucleases (aRNases, small organic
      compounds that exhibit ribonuclease activity in vitro). We demonstrate that the
      incubation of TBEV with aRNases lead to the total inactivation of the virus as
      indicated by the plaque formation assay data, but retain the viral immunogenic
      properties, as shown by the ELISA data. We propose that a possible mechanism of
      TBEV inactivation with aRNase, which includes: i) formation of local breaks in
      the lipid membrane of the virus caused by aRNase, ii) penetration of aRNase into
      the viral capsid, iii) degradation of genomic RNA by aRNase. These data suggest
      that the proposed approach can be used in the production of killed-virus vaccine.

PMID- 22872802
TI  - Control of Campylobacter spp. and Yersinia enterocolitica by virulent
      bacteriophages.
AB  - The efficacy of the Campylobacter (C.) phages NCTC12684 (group II) and CP81
      (group III) and of the Yersinia (Y.) phage PY100 to reduce the numbers of
      Campylobacter and Y. enterocolitica in meat at 4(o)C applying different
      Multiplicities of Infection (MOIs) was analyzed. Initial experiments were carried
      out in broth at 4(o)C and 37(o)C to compare cell number reductions under chilling
      and optimized growth conditions, respectively. The results showed a 1 log(10)
      unit reduction of Campylobacter cell numbers at 37(o)C in broth. However, no
      reduction was observed in broth and meat at 4(o)C. In contrast, Y. enterocolitica
      cell numbers were reduced in broth at 4(o)C (up to 3 log(10) units after 24hr)
      and 37(o)C (5 log(10) units after 1.5hr) and also in meat at 4(o)C (2 log(10)
      units after 48hr). The highest cell number reductions were obtained at the
      highest MOIs.

PMID- 22872803
TI  - The role of regulated clinical trials in the development of bacteriophage
      therapeutics.
AB  - Antibiotic resistance is now recognized as a major, global threat to human health
      and the need for the development of novel antibacterial therapies has become
      urgent. Lytic bacteriophages (phages) targeting individual bacterial pathogens
      have therapeutic potential as an alternative or adjunct to antibiotic use.
      Bacteriophage therapy has been used for decades, but clinical trials in this
      field are rare, leaving many questions unanswered as to its effectiveness for
      many infectious diseases. As a consequence bacteriophage therapy is not used or
      accepted in most parts of the world. The increasing need for new antimicrobial
      therapies is driving the development of bacteriophage therapies for a number of
      diseases but these require the successful completion of large-scale clinical
      trials in accordance with US FDA or European EMA guidelines. Bacteriophages are
      considered as biological agents by regulatory authorities and they are managed by
      biological medicinal products guidelines for European trials and guidelines of
      the division of vaccines and related product applications in the USA.
      Bacteriophage therapy is typically an 'active' treatment requiring multiplication
      in the bacterial host and therefore the factors that govern its success are
      different from those of conventional antibiotics. From the pharmacokinetic and
      pharmacodynamic points of view, time of treatment, dosage depending on the site
      of infection and the composition of the bacteriophage formulation (single vs
      multiple strains) need careful consideration when designing clinical trials.
      Scientific evidence regarding inflammatory effects, potential for gene transfer
      and phage resistance, need to be evaluated through such trials. However purity,
      stability and sterility of preparations for human use can be addressed through
      Good Manufacturing Practises to reduce many potential safety concerns. In this
      review we discuss the potential for the development of bacteriophage therapy in
      the context of critical aspects of modern, regulated clinical trials.

PMID- 22872804
TI  - Variable ligand- and receptor-binding hot spots in key strains of influenza
      neuraminidase.
AB  - Influenza A continues to be a major public health concern due to its ability to
      cause epidemic and pandemic disease outbreaks in humans. Computational
      investigations of structural dynamics of the major influenza glycoproteins,
      especially the neuraminidase (NA) enzyme, are able to provide key insights beyond
      what is currently accessible with standard experimental techniques. In
      particular, all-atom molecular dynamics simulations reveal the varying degrees of
      flexibility for such enzymes. Here we present an analysis of the relative
      flexibility of the ligand- and receptor-binding area of three key strains of
      influenza A: highly pathogenic H5N1, the 2009 pandemic H1N1, and a human N2
      strain. Through computational solvent mapping, we investigate the various ligand-
      and receptor-binding "hot spots" that exist on the surface of NA which interacts
      with both sialic acid receptors on the host cells and antiviral drugs. This
      analysis suggests that the variable cavities found in the different strains and
      their corresponding capacities to bind ligand functional groups may play an
      important role in the ability of NA to form competent reaction encounter
      complexes with other species of interest, including antiviral drugs, sialic acid
      receptors on the host cell surface, and the hemagglutinin protein. Such
      considerations may be especially useful for the prediction of how such complexes
      form and with what binding capacity.

PMID- 22872805
TI  - 'Triglyceride effect' on the dynamics of plasma lipoproteins and its possible
      link to atherogenesis.

PMID- 22872806
TI  - Extinction risk and overfishing: reconciling conservation and fisheries
      perspectives on the status of marine fishes.
AB  - Anthropogenic disturbances are ubiquitous in the ocean, but their impacts on
      marine species are hotly debated. We evaluated marine fish statuses using
      conservation (Red List threatened or not) and fisheries (above or below reference
      points) metrics, compared their alignment, and diagnosed why discrepancies arise.
      Whereas only 13.5% of Red Listed marine fishes (n = 2952) are threatened, 40% and
      21% of populations with stock assessments (n = 166) currently are below their
      more conservative and riskier reference points, respectively. Conservation and
      fisheries metrics aligned well (70.5% to 80.7%), despite their mathematical
      disconnect. Red Listings were not biased towards exaggerating threat status, and
      egregious errors, where populations were categorized at opposite extremes of
      fisheries and conservation metrics, were rare. Our analyses suggest conservation
      and fisheries scientists will agree on the statuses of exploited marine fishes in
      most cases, leaving only the question of appropriate management responses for
      populations of mutual concern still unresolved.

PMID- 22872807
TI  - Biphoton generation in quadratic waveguide arrays: a classical optical
      simulation.
AB  - Quantum entanglement became essential in understanding the non-locality of
      quantum mechanics. In optics, this non-locality can be demonstrated on
      impressively large length scales, as photons travel with the speed of light and
      interact only weakly with their environment. Spontaneous parametric down
      conversion (SPDC) in nonlinear crystals provides an efficient source for
      entangled photon pairs, so-called biphotons. However, SPDC can also be
      implemented in nonlinear arrays of evanescently coupled waveguides which allows
      the generation and the investigation of correlated quantum walks of such
      biphotons in an integrated device. Here, we analytically and experimentally
      demonstrate that the biphoton degrees of freedom are entailed in an additional
      dimension, therefore the SPDC and the subsequent quantum random walk in one
      dimensional arrays can be simulated through classical optical beam propagation in
      a two-dimensional photonic lattice. Thereby, the output intensity images directly
      represent the biphoton correlations and exhibit a clear violation of a Bell-like
      inequality.

PMID- 22872809
TI  - Surface engineering of nanoparticles in suspension for particle based bio
      sensing.
AB  - Surface activation of nanoparticles in suspension using amino organosilane has
      been carried out via strict control of a particle surface ad-layer of water using
      a simple but efficient protocol 'Tri-phasic Reverse Emulsion' (TPRE). This
      approach produced thin and ordered layers of particle surface functional groups
      which allowed the efficient conjugation of biomolecules. When used in bio-sensing
      applications, the resultant conjugates were highly efficient in the hybrid
      capture of complementary oligonucleotides and the detection of food borne
      microorganism. TPRE overcomes a number of fundamental problems associated with
      the surface modification of particles in aqueous suspension viz. particle
      aggregation, density and organization of resultant surface functional groups by
      controlling surface condensation of the aminosilane. The approach has potential
      for application in areas as diverse as nanomedicine, to food technology and
      industrial catalysis.

PMID- 22872808
TI  - Akt signaling-associated metabolic effects of dietary gold nanoparticles in
      Drosophila.
AB  - Gold nanoparticles (AuNPs) are often used as vehicles to deliver drugs or
      biomolecules, due to their mild effect on cell survival and proliferation.
      However, little is known about their effect on cellular metabolism. Here we
      examine the in vivo effect of AuNPs on metabolism using Drosophila as a model.
      Drosophila and vertebrates possess similar basic metabolic functions, and a
      highly conserved PI3K/Akt/mTOR signaling pathway plays a central role in the
      regulation of energy metabolism in both organisms. We show that dietary AuNPs
      enter the fat body, a key metabolic tissue in Drosophila larvae. Significantly,
      larvae fed with AuNP show increased lipid levels without triggering stress
      responses. In addition, activities of the PI3K/Akt/mTOR signaling pathway and
      fatty acids synthesis are increased in these larvae. This study thus reveals a
      novel function of AuNPs in influencing animal metabolism and suggests its
      potential therapeutic applications for metabolic disorders.

PMID- 22872810
TI  - Physicochemical biology: conquered boundaries and new horizons.
AB  - In this paper, we shall consider the main evolutionary stages that occurred
      within the field of physicochemical biology during the 20th century, following
      the determination of the tertiary structure of DNA by Watson and Crick and the
      subsequent successes in the X-ray structural analysis of biopolymers. The
      authors' ideas on the pre-emptive problems and the methods used in
      physicochemical biology in the 21st century are also presented, including an
      investigation of the dynamics of biochemical processes, studies of the functions
      of unstructured proteins, as well as single-molecule investigations of enzymatic
      processes and of biopolymer tertiary structure formation.

PMID- 22872813
TI  - Contribution of the TGFB1 Gene ?to Myocardial Infarction Susceptibility.
AB  - Carriage frequencies of alleles and genotypes of theTGFB1 gene polymorphous loci 
      509C>T (rs1800469), 869T>C (rs1982073), 915G>C (rs1800471), which affect the
      level of cytokine TGF-beta1 production, were analyzed in the patients of Russian
      ethnic descent with myocardial infarction (MI) (406 cases) and in the control
      group of the same ethnic descent (198 controls). Significant association with MI
      was observed in carriage frequencies of the alleleTGFB1*-509T (p=0.046, OR =1.45,
      95% CI: 1.02-2.06), genotypes TGFB1*869T/T (p=0.0024, OR =1.75, 95% CI: 1.22
      2.51), andTGFB1*915G/G (p=0.048, OR=1.76, 95% CI: 1.05-2.97). Linkage
      disequilibrium analysis for these SNPs has shown that the associations revealed
      can be considered to be independent. A complex analysis of MI association with
      combinations of alleles/genotypes of said SNPs indicates their cumulative effect.
      An analysis of susceptibility to early-onset MI (<= 50 years old) revealed a
      positive association of the alleleTGFB1*-509T (p=0.002, OR=2.24, 95% CI: 1.35
      3.71) and genotypeTGFB1*869T/T (p=0.008, OR=1.93, 95% CI: 1.18-3.15), as well as
      their additivity. An analysis of susceptibility to recurrent MI revealed an
      association of the genotypeTGFB1*-509T/T (p=0.0078, OR=2.60, 95% CI: 1.28-5.28).
      The results obtained indicate the important role of theTGFB1gene in
      susceptibility to MI, including early-onset and recurrent MI, in Russians.

PMID- 22872812
TI  - Coagulation Factor IX for Hemophilia B Therapy.
AB  - Factor IX is a zymogen enzyme of the blood coagulation cascade. Inherited absence
      or deficit of the IX functional factor causes bleeding disorder hemophilia B,
      which requires constant protein replacement therapy. Reviewed herein are the
      current state in the manufacturing of FIX, improved variants of the recombinant
      protein for therapy, transgenic organisms for obtaining FIX, and the advances in
      the gene therapy of hemophilia B.

PMID- 22872814
TI  - Construction of a Full-Atomic Mechanistic Model of Human Apurinic/Apyrimidinic
      Endonuclease APE1 for Virtual Screening of Novel Inhibitors.
AB  - A full-atomic molecular model of human apurinic/apyrimidinic endonuclease APE1,
      an important enzyme in the DNA repair system, has been constructed. The research
      consisted of hybrid quantum mechanics/molecular mechanics modeling of the enzyme
      substrate interactions, as well as calculations of the ionization states of the
      amino acid residues of the active site of the enzyme. The choice of the APE1
      mechanism with an Asp210 residue as a proton acceptor was validated by means of a
      generalization of modeling and experimental data. Interactions were revealed in
      the active site that are of greatest significance for binding the substrate and
      potential APE1 inhibitors (potential co-drugs of interest in the chemo- and
      radiotherapy of oncological diseases).

PMID- 22872811
TI  - Telomere lengthening and other functions of telomerase.
AB  - Telomerase is an enzyme that maintains the length of the telomere. The telomere
      length specifies the number of divisions a cell can undergo before it finally
      dies (i.e. the proliferative potential of cells). For example, telomerase is
      activated in embryonic cell lines and the telomere length is maintained at a
      constant level; therefore, these cells have an unlimited fission potential. Stem
      cells are characterized by a lower telomerase activity, which enables only
      partial compensation for the shortening of telomeres. Somatic cells are usually
      characterized by the absence of telomerase activity. Telomere shortening leads to
      the attainment of the Hayflick limit, the transition of cells to a state of
      senescence. The cells subsequently enter a state of crisis, accompanied by
      massive cell death. The surviving cells become cancer cells, which are capable
      both of dividing indefinitely and maintaining telomere length (usually with the
      aid of telomerase). Telomerase is a reverse transcriptase. It consists of two
      major components: telomerase RNA (TER) and reverse transcriptase (TERT). TER is a
      non-coding RNA, and it contains the region which serves as a template for
      telomere synthesis. An increasing number of articles focussing on the alternative
      functions of telomerase components have recently started appearing. The present
      review summarizes data on the structure, biogenesis, and functions of telomerase.

PMID- 22872815
TI  - Comprehensive carrier screening and molecular diagnostic testing for recessive
      childhood diseases.
AB  - Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and
      have an established molecular basis. Although individually uncommon, Mendelian
      diseases collectively account for ~20% of infant mortality and ~18% of pediatric
      hospitalizations. Molecular diagnostic testing is currently available for only
      ~300 recessive disorders. Preconception screening, together with genetic
      counseling of carriers, has resulted in remarkable declines in the incidence of
      several severe recessive diseases including Tay-Sachs disease and cystic
      fibrosis. However, extension of preconception screening and molecular diagnostic
      testing to most recessive disease genes has hitherto been impractical. Recently,
      we reported a preconception carrier screen / molecular diagnostic test for 448
      recessive childhood diseases. The current status of this test is reviewed here.
      Currently, this reports analytical validity of the comprehensive carrier test. As
      the clinical validity and clinical utility in the contexts described is
      ascertained, this article will be updated.

PMID- 22872816
TI  - Genetic testing for long QT syndrome and the category of cardiac ion
      channelopathies.
AB  - Cardiac ion channel mutational analysis is a category of genetic testing used in
      clinical practice for determining the status of long QT syndrome, short QT
      syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada
      syndrome genes in blood, saliva, or tissue from patients and family members at
      risk for cardiac events such as syncope and sudden death. Such testing is most
      informative following careful phenotypic characterization. Individuals with ion
      channelopathies may benefit from prevention (avoidance of triggers and
      predisposing drugs) and treatment (e.g., beta blocker therapy, implantable
      cardioverter-defibrillator (ICD) placement) modalities.

PMID- 22872817
TI  - Structural and Magnetic Characterization of Superparamagnetic Iron Platinum
      Nanoparticle Contrast Agents for Magnetic Resonance Imaging.
AB  - We report the synthesis, from simple salts, and the physical characterization of
      superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as
      contrast agents in magnetic resonance imaging. The properties of these particles
      were determined by means of transmission electron microscopy (TEM),
      thermogravimetric analysis (TGA), inductively coupled plasma-optical emission
      spectroscopy (ICP-OES), superconducting quantum interference device (SQUID)
      magnetometry, and nuclear magnetic resonance (NMR) relaxivity at 4.7 Tesla. TEM
      showed that the diameters of the particles ranged from 9.3 nm to 10 nm, depending
      on the mole ratio of iron to platinum precursors, and on the concentration of
      Octadecylamine (ODA) used in their preparation. The iron to platinum
      stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly
      dependant on the initial mole ratios of iron and platinum salts, as well as on
      the concentration of ODA in the reaction. SQUID magnetometry showed that the
      SIPPs were superparamagnetic and had magnetic moments that increased with
      increasing iron content from 62 to 72 A*m(2)/kg Fe. The measured relaxivities of
      the SIPPs at 4.7 Tesla were higher than commercially available superparamagnetic
      iron oxide nanoparticles (SPIONs), suggesting that these particles may be
      superior contrast agents in T(2)-weighted magnetic resonance imaging (MRI).

PMID- 22872818
TI  - Health care utilization and medical costs for childhood asthma in Taiwan: using
      Taiwan National Health Insurance Research Database.
AB  - Asthma is an important health problem worldwide and the prevalence is increasing
      in most part of the world. The burden of this disease to governments, health-care
      systems, and patients and their families have been greater more than ever despite
      efforts advocated by Global Initiative for Asthma for total asthma controls.
      Using Taiwan National Health Insurance Research Database, in this review, the
      population-based prospective studies showed the costs and health care utilization
      of childhood asthma in Taiwan was 2 folds higher than non-asthmatic children, and
      the prescription patterns of anti-asthmatic medications among physician in
      different discipline were all far from satisfied. The appropriateness of
      combinational therapy of inhaled corticosteroids and long acting beta-agonists
      for moderate to severe childhood asthma was only 62%. In a government-sponsored
      disease management program for asthmatic patients within national health
      insurance, though the total mean costs (26.5%) and outpatient costs (26.1%)
      increased, the mean emergency department visits and hospitalization rates were
      significantly reduced by 34.4% and 51.74%, respectively, compared to the previous
      year. Therefore, in the real-world situation, asthmatic patients as well as
      medical professions who take care of asthmatic children still have much space for
      their symptoms controls and knowledge improvement to reduce the burden of asthma.
      From the experience of care and management of childhood asthma in Taiwan may
      reveal same problems of childhood asthma care in the similar cultural and
      ecological environments of Asian pacific countries, and suggest government
      sponsored program may also have significant impact aimed at improving the care of
      patients with asthma.

PMID- 22872819
TI  - Occupational asthma in Japan.
AB  - Research into occupational asthma (OA) in Japan has been led by the Japanese
      Society of Occupational and Environmental Allergy. The first report about
      allergic OA identified konjac asthma. After that, many kinds of OA have been
      reported. Cases of some types of OA, such as konjac asthma and sea squirt asthma,
      have been dramatically reduced by the efforts of medical personnel. Recently,
      with the development of new technologies, chemical antigen-induced asthma has
      increased in Japan. Due to advances in anti-asthma medication, control by medical
      treatment tends to be emphasized and the search for causative antigens seems to
      be neglected. Furthermore, we do not have a Japanese guideline for diagnosis and
      management of OA. This article discusses the current state of OA in Japan.

PMID- 22872820
TI  - House dust mite sensitization in toddlers predict persistent wheeze in children
      between eight to fourteen years old.
AB  - BACKGROUND: Identifying toddlers at increased risk of developing persistent
      wheeze provides an opportunity for risk-reducing interventions. House dust mite
      (HDM) allergen sensitization might identify this group of high-risk children.
      OBJECTIVE: We examined whether a positive skin prick test (SPT) to at least 1 of
      the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze
      at age 8 to 14 years old. METHODS: A cohort of 78 children, who had wheezing
      episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were
      enrolled. SPT results were obtained from the National University Hospital
      database. Four to 9 years later, the children, currently between 8 to 14 years
      old, were re-assessed for persistence of asthma symptoms and other atopic
      disorders via a telephone interview. A validated questionnaire on current
      wheezing and asthma, developed by the International Study of Asthma and Allergies
      in Childhood, was used. Fisher's exact test was used to evaluate the association
      between persistence of asthma and a positive SPT. RESULTS: Of the 78 children who
      participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a
      negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative
      children had persistence of asthma symptoms. There is a significant association
      between a positive SPT during the preschool years, and persistence of asthma (p =
      0.0314 [<0.05]). CONCLUSION: HDM sensitization at ages 2 to 5 years old in
      wheezing children predicts persistence of asthma after 4 to 9 years. This in turn
      may have benefits for management of asthma in this high-risk group.

PMID- 22872821
TI  - Lack of efficacy of a herbal preparation (RCM-102) for seasonal allergic
      rhinitis: a double blind, randomised, placebo-controlled trial.
AB  - BACKGROUND: A herbal preparation, known as RMIT Chinese Medicine 102 (RCM-102)
      consisting of eight herbs which demonstrates inhibition of the release of key
      inflammatory mediators associated with seasonal allergic rhinitis (SAR) was used.
      This study evaluated the efficacy and safety of RCM-102 for SAR. OBJECTIVE: This
      study evaluated the efficacy and safety of RCM-102 for SAR. METHODS: This
      randomised placebo-controlled trial involved subjects aged between 18 and 65 who
      were randomly assigned to either RCM-102 or a placebo group. After a two-week
      baseline period, all subjects took either RCM-102 or placebo capsules (two
      capsules each time, three times daily with a four hour interval) for a period of
      eight weeks. The primary end-points were the Five-Point Scale symptom scores.
      Rhinoconjunctivitis Quality of Life Questionnaire, relief medication usage,
      adverse events, kidney and liver function tests and full blood examination were
      secondary end-points. Intention-to-treat analysis was applied. RESULTS: One
      hundred and four subjects were randomised with 52 in each group. Ninety-five
      subjects (47 and 48 subjects in RCM-102 and placebo groups) completed the trial.
      Nine subjects withdrew from the study prior to the end of the second treatment
      week. At the end of the trial, there were no significant differences between the
      two groups with respect to all outcome measures. There were no liver or kidney
      function abnormalities reported. CONCLUSION: This mechanism-based RCM-102 was
      safe but not more beneficial than placebo for patients with SAR.

PMID- 22872822
TI  - Measurement of Hymenoptera venom specific IgE by the IMMULITE 3gAllergy in
      subjects with negative or positive results by ImmunoCAP.
AB  - BACKGROUND: Patients may receive negative results from a specific IgE (sIgE) test
      such as the ImmunoCAP (CAP) despite a documented history of systemic reaction to
      a Hymenoptera sting. Thus, further testing may be required using another
      serological method or venom skin prick tests to confirm allergy diagnosis and
      correct species. OBJECTIVE: To evaluate the sensitivity and the specificity of
      CAP and IMMULITE 3gAllergy (IMMULITE) for detecting sIgE to Paper wasp (WA) and
      Yellow Jacket (YJ) venoms using patient clinical history as the comparator.
      METHODS: Sera from 70 participants with a history of systemic reactions (SR) to
      WA and/or YJ stings were tested using CAP and IMMULITE. Fifty participants from
      this group had negative results on CAP. To assess specificity, sera from 71
      participants who had never experienced either a WA or YJ sting were tested using
      CAP and IMMULITE. Fifty participants from this group tested positive using CAP.
      RESULTS: In participants with a history of systemic reaction to a Hymenoptera
      sting, yet who tested negative for WA and/or YJ sIgE according to CAP, the
      positivity rate according to IMMULITE was 20-42% using 0.10 IU(A)/mL as the limit
      of detection (LoD), per the manufacturer's specification. When the LoD for CAP
      (0.35 IU(A)/mL) was applied to the IMMULITE results, positivity according to
      IMMULITE was 14-26%. Overall, sensitivity, specificity, and agreement with SR
      were greater for IMMULITE than for CAP. For YJ: sensitivity (IMMULITE:CAP),
      42.8%:28.5%; specificity, 53.5%:39.4%; agreement, 48.2%:34%. For WA, sensitivity
      (IMMULITE:CAP), 58.6%:28.5%; specificity, 49.3%:47.8%; agreement, 43.9%:38.3%.
      CONCLUSION: The IMMULITE performed well for detecting sIgE to Hymenoptera venom.

PMID- 22872823
TI  - Recent progress of elucidating the mechanisms of drug hypersensitivity.
AB  - Recent technical approaches to investigating drug hypersensitivity have provided
      a great deal of information to solve the mechanisms that remain poorly
      understood. First, immunological investigations and in silico analysis have
      revealed that a novel interaction between T cells and antigen-presenting cells,
      namely the pharmacological interaction concept, is involved in drug recognition
      and the hapten theory. Second, progress in immunology has provided a new concept
      of CD4+ T cell subsets. Th17 cells have proven to be a critical player in acute
      generalized exanthematous pustulosis. Our recent findings suggest that this
      subset might contribute to the pathogenesis of Stevens-Johnson syndrome/toxic
      epidermal necrolysis. Third, alarmins, molecules associated with innate immunity,
      are also associated with exaggeration and the persistence of severe drug
      hypersensitivity. The latest innovative techniques are providing a new landscape
      to examine drug hypersensitivity.

PMID- 22872824
TI  - An aerobiological perspective in allergy and asthma.
AB  - Allergic diseases are amongst the most common chronic disorders worldwide. Today,
      more than 300 million of the population is known to suffer from one or other
      allergic ailments affecting the socio-economic quality of life. Major causative
      agents implicated are pollen grains, fungal spores, dust mites, insect debris,
      animal epithelia, etc. Several aerobiological studies have been conducted in
      different parts of the world to ascertain aerial concentration and seasonality of
      pollen grains and fungi. Especially from clinical point of view, it is important
      to know the details about the pollen season and pollen load in the atmosphere.
      The flowering time of higher plants are events that come periodically in each
      season, but the time of blooming may differ from year to year, in different
      geographic locations. Based on differences recorded in several years of
      observations in airborne pollen, pollen calendars are drawn as an aid to allergy
      diagnosis and management. This review article emphasises on various
      aerobiological parameters of environmental pollen from different parts of the
      world with special emphasis from India. The role of aerobiology in the diagnosis
      and management of allergic diseases is reviewed briefly in this article.

PMID- 22872825
TI  - Gianotti-Crosti syndrome: case report of a pruritic acral exanthema in a child.
AB  - Gianotti-Crosti syndrome (GCS) is a sporadic dermatosis affecting mainly
      children. It is characterized by multiple, confluent, monomorphic and pruritic
      pink to red-brown papules or papulovesicles, distributed symmetrically on the
      face, extensor surfaces of the extremities and buttocks, commonly sparing the
      trunk, palms and soles. This can be preceded by a viral infection, and may be
      accompanied by fever, hepatosplenomegaly, or lymphadenopathy. Personal and family
      history of atopy appears to be a risk factor in the subsequent development of
      GCS, thus frequently diagnosed as atopic dermatitis. We report a case of a 4-year
      old boy from our institution with generalized, pruritic, papulovesicular rashes
      on the face and extremities for one month. He was diagnosed to have atopic
      dermatitis and treated as such, before presentation to our institution. As the
      signs and symptoms in GCS are similar to atopic dermatitis, we suggest that this
      diagnosis be considered when presented with a similar case.

PMID- 22872826
TI  - Chronic urticaria and use of statins.

PMID- 22872827
TI  - The value of originality and proper quotation.

PMID- 22872828
TI  - Overview of mandibular condyle fracture.
AB  - The mandibular condyle is a region that plays a key role in the opening and
      closing of the mouth, and because fracture causes functional and aesthetic
      problems such as facial asymmetry, it is very important to perform accurate
      reduction. Traditionally, there has been disagreement on how to manage fracture
      of the mandibular condyle. This review explores the misunderstanding of
      mandibular condyle fracture treatment and modern-day treatment strategies.

PMID- 22872829
TI  - Surgical management of a mandible subcondylar fracture.
AB  - Open reduction and anatomic reduction can create better function for the
      temporomandibular joint, compared with closed treatment in mandible fracture
      surgery. Therefore, the double miniplate fixation technique via mini
      retromandibular incision was used in order to make the most stable fixation when
      performing subcondylar fracture surgery. Those approaches provide good
      visualization of the subcondyle from the posterior edge of the ramus, allow the
      surgeon to work perpendicularly to the fracture, and enable direct fracture
      management. Understanding the biomechanical load in the fixation of subcondylar
      fractures is also necessary in order to optimize fixation methods. Therefore, we
      measured the biomechanical loads of four different plate fixation techniques in
      the experimental model regarding mandibular subcondylar fractures. It was found
      that the loads measured in the two-plate fixation group with one dynamic
      compression plate (DCP) and one adaption plate showed the highest deformation and
      failure loads among the four fixation groups. The loads measured in the one DCP
      plate fixation group showed higher deformation and failure loads than the loads
      measured in the two adaption plate fixation group. Therefore, we conclude that
      the selection of the high profile plate (DCP) is also important in order to
      create a stable load in the subcondylar fracture.

PMID- 22872830
TI  - Current concepts in the mandibular condyle fracture management part I: overview
      of condylar fracture.
AB  - The incidence of condylar fractures is high, but the management of fractures of
      the mandibular condyle continues to be controversial. Historically,
      maxillomandibular fixation, external fixation, and surgical splints with internal
      fixation systems were the techniques commonly used in the treatment of the
      fractured mandible. Condylar fractures can be extracapsular or intracapsular,
      undisplaced, deviated, displaced, or dislocated. Treatment depends on the age of
      the patient, the co-existence of other mandibular or maxillary fractures, whether
      the condylar fracture is unilateral or bilateral, the level and displacement of
      the fracture, the state of dentition and dental occlusion, and the surgeonnds on
      the age of the patient, the co-existence of othefrom which it is difficult to
      recover aesthetically and functionally;an appropriate treatment is required to
      reconstruct the shape and achieve the function ofthe uninjured status. To do
      this, accurate diagnosis, appropriate reduction and rigid fixation, and
      complication prevention are required. In particular, as mandibular condyle
      fracture may cause long-term complications such as malocclusion, particularly
      open bite, reduced posterior facial height, and facial asymmetry in addition to
      chronic pain and mobility limitation, great caution should be taken. Accordingly,
      the authors review a general overview of condyle fracture.

PMID- 22872831
TI  - Current Concepts in the Mandibular Condyle Fracture Management Part II: Open
      Reduction Versus Closed Reduction.
AB  - In the treatment of mandibular condyle fracture, conservative treatment using
      closed reduction or surgical treatment using open reduction can be used.
      Management of mandibular condylar fractures remains a source of ongoing
      controversy in oral and maxillofacial trauma. For each type of condylar
      fracture,the treatment method must be chosen taking into consideration the
      presence of teeth, fracture height, patient'sadaptation, patient's masticatory
      system, disturbance of occlusal function, and deviation of the mandible. In the
      past, closed reduction with concomitant active physical therapy conducted after
      intermaxillary fixation during the recovery period had been mainly used, but in
      recent years, open treatment of condylar fractures with rigid internal fixation
      has become more common. The objective of this review was to evaluate the main
      variables that determine the choice of an open or closed method for treatment of
      condylar fractures, identifying their indications, advantages, and disadvantages,
      and to appraise the current evidence regarding the effectiveness of interventions
      that are used in the management of fractures of the mandibular condyle.

PMID- 22872832
TI  - Application of virtual surgical planning with computer assisted design and
      manufacturing technology to cranio-maxillofacial surgery.
AB  - Computer aided design and manufacturing (CAD/CAM) technology today is the
      standard in manufacturing industry. The application of the CAD/CAM technology,
      together with the emerging 3D medical images based virtual surgical planning
      (VSP) technology, to craniomaxillofacial reconstruction has been gaining
      increasing attention to reconstructive surgeons. This article illustrates the
      components, system and clinical management of the VSP and CAD/CAM technology
      including: data acquisition, virtual surgical and treatment planning, individual
      implant design and fabrication, and outcome assessment. It focuses primarily on
      the technical aspects of the VSP and CAD/CAM system to improve the predictability
      of the planning and outcome.

PMID- 22872833
TI  - Comparison of the wound healing effect of cellulose and gelatin: an in vivo
      study.
AB  - BACKGROUND: Many topical hemostatics are widely applied for bleeding control.
      They can be classified into two categories according to their mechanism of action
      on the clotting cascade in a biologically active or passive manner. Passive
      hemostatics include cellulose and gelatin. We performed an experimental study to
      compare the effect of passive hemostatics in wound healing by applying them to a
      rectus abdominis muscle defect of white mice. METHODS: Surgicel is a sterile
      absorbable knitted fabric prepared by the controlled oxidation of regenerated
      cellulose. Spongostan is an absorbable hemostatic gelatin sponge. In 30 mice, a
      1*1 cm defect was created on the rectus abdominis muscle and the materials were
      applied in three ways: control group, cellulose (Surgicel) group, gelatin
      (Spongostan) group. For the histologic analysis, biopsies were performed at 3 and
      28 days. RESULTS: After 3 days, the cellulose group showed limited granulation
      formation with acute inflammatory reactions similar to the control group. At the
      28th day, moderate amounts of granulation tissue formation was observed with
      milder inflammatory reactions than the control group. In the gelatin group, after
      3 days, gelatin remnants were observed surrounded by severe inflammatory changes.
      After 28 days, the same quantity of gelatin remnants could be still observed.
      CONCLUSIONS: This study suggests that cellulose is associated with minimal
      morbidity in wound healing, while the use of gelatin shows severe adverse tissue
      reactions with delayed wound healing. Consequently, cellulose is better than
      gelatin when considering wound healing.

PMID- 22872834
TI  - Large auricular chondrocutaneous composite graft for nasal alar and columellar
      reconstruction.
AB  - BACKGROUND: Among the various methods for correcting nasal deformity, the
      composite graft is suitable for the inner and outer reconstruction of the nose in
      a single stage. In this article, we present our technique for reconstructing the
      ala and columella using the auricular chondrocutaneous composite graft. METHODS:
      From 2004 to 2011, 15 cases of alar and 2 cases of columellar reconstruction
      employing the chondrocutaneous composite graft were studied, all followed up for
      3 to 24 months (average, 13.5 months). All of the patients were reviewed
      retrospectively for the demographics, graft size, selection of the donor site and
      outcomes including morbidity and complications. RESULTS: The reasons for the
      deformity were burn scar (n=7), traumatic scar (n=4), smallpox scar (n=4), basal
      cell carcinoma defect (n=1), and scar contracture (n=1) from implant induced
      infection. In 5 cases of nostril stricture and 6 cases of alar defect and
      notching, composite grafts from the helix were used (8.9*12.5 mm). In 4 cases of
      retracted ala, grafts from the posterior surface of the concha were matched (5*15
      mm). For the reconstruction of the columella, we harvested the graft from the
      posterior scapha (9*13.5 mm). Except one case with partial necrosis and delayed
      healing due to smoking, the grafts were successful in all of the cases and there
      was no deformity of the donor site. CONCLUSIONS: An alar and columellar defect
      can be reconstructed successfully with a relatively large composite graft without
      donor site morbidity. The selection of the donor site should be individualized
      according to the 3-dimensional configuration of the defect.

PMID- 22872835
TI  - A study on the genetic inheritance of ankyloglossia based on pedigree analysis.
AB  - BACKGROUND: Ankyloglossia or tongue-tie is a congenital anomaly characterized by
      an abnormally short lingual frenum. Its prevalence in the newborn population is
      approximately 4%. Its mode of inheritance has been studied in some articles, but
      no conclusion has been established. Also, no relevant report has been published
      in Korea. This study was conducted to elucidate the genetic inheritance of
      ankyloglossia via pedigree analysis. METHODS: In this study, 149 patients with no
      other congenital anomaly who underwent frenuloplasty between March 2001 and March
      2010 were studied. Pedigrees were made via pre- or post-operative history taking,
      and patients with uncertain histories were excluded. In the patient group that
      showed a hereditary nature, the male-to-female ratio, inheritance rate, and
      pattern of inheritance were investigated. RESULTS: One hundred (67.11%) of the
      patients were male and 49 (32.89%) were female (male-female ratio=2.04:1). Ninety
      one (61.07%) patients reported no other relative with ankyloglossia, and 58
      (38.93%) patients had a relative with this disease. The inheritance rate was
      20.69% in the 58 cases with a hereditary nature. In the group with no family
      history of ankyloglossia, the male-female ratio was 3.79:1, which significantly
      differed from that of the group with a family history of ankyloglossia. X
      chromosome mediated inheritance and variation in the gene expression was revealed
      in the pedigree drawn for the groups with hereditary ankyloglossia. CONCLUSIONS:
      Ankyloglossia has a significant hereditary nature. Our data suggest X-linked
      inheritance. This study with 149 patients, the first in Korea, showed X-linked
      inheritance in patients with a sole anomaly.

PMID- 22872836
TI  - Osteoplastic Reconstruction of Post-enucleatic Microorbitalism.
AB  - BACKGROUND: Patients who have undergone enucleation during infancy due to
      retinoblastoma can develop microorbitalism due to the decreased growth
      stimulation from the eyeball and the surrounding soft tissues. Anatomically, the
      orbit consist of parts of the frontal bone superiorly, the maxilla inferiorly,
      the ethmoid bone medially, and the zygoma laterally. Considering the possibility
      of surgically expanding the orbit using tripod osteotomy, in this study we
      conducted tripod osteotomy on adult patients with microorbitalism of
      retinoblastoma. METHODS: Tripod osteotomy was conducted to expand the orbital
      volume in adult patients with microorbitalism due to enucleation in infancy for
      retinoblastoma. The orbital volume was measured using the Aquarius Workstation
      ver. 4.3.6 and the orbit width was measured with preoperative and postoperative 3
      dimensional facial bone computed tomography (CT) imaging. Preoperative and
      postoperative photographs were used to visualize the difference produced by the
      surgery. RESULTS: The orbital volume of the affected side was 10.3 cm(3) before
      and 12.5 cm(3) after the surgery, showing an average increase in volume of 2.2
      cm(3) (21.4%). The increase in the obital width was confirmed by the preoperative
      and postoperative 3-dimensional facial CT images and aesthetic improvement was
      observed by the preoperative and postoperative photographs. CONCLUSIONS: Tripod
      osteotomy, which realigns the orbital bone, zygoma, and maxilla, is used to
      correct posttraumatic malunion as well as non-traumatic congenital abnormalities
      such as that seen in facial cleft. We applied this procedure in microorbitalism
      secondary to enucleation for retinoblastoma to allow orbital expansion and
      correct asymmetry.

PMID- 22872837
TI  - Outcome analysis of cranial molding therapy in nonsynostotic plagiocephaly.
AB  - BACKGROUND: It is known that nonsynostotic plagiocephaly does not spontaneously
      improve, and the craniofacial deformities that result from it. This study was
      conducted to analyze the effectiveness of helmet therapy for the nonsynostotic
      plagiocephaly patient, and to suggest a new treatment strategy based on this
      analysis. METHODS: A total of 108 pediatric patients who had undergone helmet
      therapy after being diagnosed with nonsynostotic plagiocephaly were included in
      this study. The patients were classified according to the initiation age of the
      helmet therapy, severity, and helmet wearing time. The treatment effect was
      compared using cranial vault asymmetry (CVA) and the cranial vault asymmetry
      index (CVAI), which were obtained from diagonal measurements before and after
      therapy. RESULTS: The discrepancy of CVA and CVAI of all the patients
      significantly decreased after helmet therapy. According to the initiation time of
      helmet therapy, the treatment effect was best at 5 months old or less. The helmet
      wearing time per day was proportional to the treatment effect up to 20 hours. In
      addition, the rate of the successful treatment (final CVA <=5 mm) significantly
      decreased when the initiation age was 9.1 months or older and the treatment
      period was less than 7.83 months. CONCLUSIONS: This study showed the
      effectiveness of the helmet therapy for nonsynostotic plagiocephaly patients.
      Based on analysis of this study, helmet therapy should be started at the age of 9
      months or younger for 7.83 months or more, and the helmet wearing time should be
      more than 20 hours a day.

PMID- 22872838
TI  - Anterior cranial base reconstruction with a reverse temporalis muscle flap and
      calvarial bone graft.
AB  - BACKGROUND: Cranial base defects are challenging to reconstruct without serious
      complications. Although free tissue transfer has been used widely and
      efficiently, it still has the limitation of requiring a long operation time along
      with the burden of microanastomosis and donor site morbidity. We propose using a
      reverse temporalis muscle flap and calvarial bone graft as an alternative option
      to a free flap for anterior cranial base reconstruction. METHODS: Between April
      2009 and February 2012, cranial base reconstructions using an autologous
      calvarial split bone graft combined with a reverse temporalis muscle flap were
      performed in five patients. Medical records were retrospectively analyzed and
      postoperative computed tomography scans, magnetic resonance imaging, and
      angiography findings were examined to evaluate graft survival and flap viability.
      RESULTS: The mean follow-up period was 11.8 months and the mean operation time
      for reconstruction was 8.4+/-3.36 hours. The defects involved the anterior
      cranial base, including the orbital roof and the frontal and ethmoidal sinus. All
      reconstructions were successful. Viable flap vascularity and bone survival were
      observed. There were no serious complications except for acceptable donor site
      depressions, which were easily corrected with minor procedures. CONCLUSIONS: The
      reverse temporalis muscle flap could provide sufficient bulkiness to fill dead
      space and sufficient vascularity to endure infection. The calvarial bone graft
      provides a rigid framework, which is critical for maintaining the cranial base
      structure. Combined anterior cranial base reconstruction with a reverse
      temporalis muscle flap and calvarial bone graft could be a viable alternative to
      free tissue transfer.

PMID- 22872839
TI  - Comparison of the Multidetector-row Computed Tomographic Angiography Axial and
      Coronal Planes' Usefulness for Detecting Thoracodorsal Artery Perforators.
AB  - BACKGROUND: During the planning of a thoracodorsal artery perforator (TDAP) free
      flap, preoperative multidetector-row computed tomographic (MDCT) angiography is
      valuable for predicting the locations of perforators. However, CT-based
      perforator mapping of the thoracodorsal artery is not easy because of its small
      diameter. Thus, we evaluated 1-mm-thick MDCT images in multiple planes to search
      for reliable perforators accurately. METHODS: Between July 2010 and October 2011,
      19 consecutive patients (13 males, 6 females) who underwent MDCT prior to TDAP
      free flap operations were enrolled in this study. Patients ranged in age from 10
      to 75 years (mean, 39.3 years). MDCT images were acquired at a thickness of 1 mm
      in the axial, coronal, and sagittal planes. RESULTS: The thoracodorsal artery
      perforators were detected in all 19 cases. The reliable perforators originating
      from the descending branch were found in 14 cases, of which 6 had transverse
      branches. The former were well identified in the coronal view, and the latter in
      the axial view. The location of the most reliable perforators on MDCT images
      corresponded well with the surgical findings. CONCLUSIONS: Though MDCT has been
      widely used in performing the abdominal perforator free flap for detecting
      reliable perforating vessels, it is not popular in the TDAP free flap. The
      results of this study suggest that multiple planes of MDCT may increase the
      probability of detecting the most reliable perforators, along with decreasing the
      probability of missing available vessels.

PMID- 22872840
TI  - Reconstruction of pretibial defect using pedicled perforator flaps.
AB  - BACKGROUND: Coverage of defects of the pretibial area remains a challenge for
      surgeons. The difficulty comes from the limited mobility and availability of the
      overlying skin and soft tissue. We applied variable pedicled perforator flaps to
      overcome the disadvantages of local flaps and free flaps on the pretibial area.
      METHODS: Eight patients who had the defects in the anterior tibial area were
      enrolled. Retrospective data were obtained on patient demographics, cause, defect
      location, defect size, flap dimension, originating artery, pedicle length,
      pedicle rotation, complication, and postoperative result. The raw surface created
      following the flap elevation was covered with a split thickness skin graft.
      RESULTS: Posterior tibial artery-based perforator flaps were used in five cases
      and peroneal artery-based perforator flaps in three cases. The mean age was 54.3
      and the mean period of follow-up was 6 months. The average size of the flaps was
      63.8 cm(2), with a range of 18 to 135 cm(2). There were no major complications.
      No patients had any newly developed functional deficit of the lower leg.
      CONCLUSIONS: We suggest that pedicled perforator flaps can be an alternative
      treatment modality for covering pretibial defects as a simple, safe and versatile
      procedure.

PMID- 22872841
TI  - Lower Extremity Reconstruction Using Vastus Lateralis Myocutaneous Flap versus
      Anterolateral Thigh Fasciocutaneous Flap.
AB  - BACKGROUND: The anterolateral thigh (ALT) perforator flap has become a popular
      option for treating soft tissue defects of lower extremity reconstruction and can
      be combined with a segment of the vastus lateralis muscle. We present a
      comparison of the use of the ALT fasciocutaneous (ALT-FC) and myocutaneous flaps.
      METHODS: We retrospectively reviewed patients in whom free-tissue transfer was
      performed between 2005 and 2011 for the reconstruction of lower extremity soft
      tissue defects. Twenty-four patients were divided into two groups: reconstruction
      using an ALT-FC flap (12 cases) and reconstruction using a vastus lateralis
      myocutaneous (VL-MC) flap (12 cases). Postoperative complications, functional
      results, cosmetic results, and donor-site morbidities were studied. RESULTS:
      Complete flap survival was 100% in both groups. A flap complication was noted in
      one case (marginal dehiscence) of the ALT-FC group, and no complications were
      noted in the VL-MC group. In both groups, one case of partial skin graft loss
      occurred at the donor site, and debulking surgeries were needed for two cases.
      There were no significant differences in the mean scores for either functional or
      cosmetic outcomes in either group. CONCLUSIONS: The VL-MC flap is able to fill
      occasional dead space and has comparable survival rates to ALT-FC with minimal
      donor-site morbidity. Additionally, the VL-MC flap is easily elevated without
      myocutaneous perforator injury.

PMID- 22872842
TI  - Outcome of management of local recurrence after immediate transverse rectus
      abdominis myocutaneous flap breast reconstruction.
AB  - BACKGROUND: No consensus has been reached regarding the outcome of management of
      local recurrence after transverse rectus abdominis myocutaneous (TRAM) flap
      breast reconstruction. This study demonstrated the presentation, management, and
      outcomes of local recurrence after immediate TRAM breast reconstruction. METHODS:
      A comparison was conducted among 1,000 consecutive patients who underwent
      immediate breast reconstruction with a pedicled TRAM flap (TRAM group) and 3,183
      consecutive patients who underwent only modified radical mastectomy without
      reconstruction (MRM group) from January 2001 to December 2009. The presentation,
      treatment, and outcome including aesthetics and overall survival rate were
      analyzed. RESULTS: Local recurrences occurred in 18 (1.8%) patients (TRAM-LR
      group) who underwent TRAM breast reconstruction and 38 (1.2%) patients (MRM-LR
      group) who underwent MRM only (P=0.1712). Wide excision was indicated in almost
      all the local recurrence cases. Skin graft was required in 4 patients in the MRM
      LR group, whereas only one patient required a skin graft to preserve the mound
      shape in the TRAM-LR group. The breast mound was maintained in all 17 patients
      that survived in the TRAM-LR group even after wide excision. The overall survival
      rate was 94.4% in the TRAM-LR group and 65.8% in the MRM-LR group (P=0.276).
      CONCLUSIONS: Local recurrence after immediate TRAM flap breast reconstruction
      could be detected without delay and managed effectively by multiple modalities
      without reducing overall survival rates. Breast mound reconstruction with soft
      autologous tissue allowed for primary closure in most of the cases. In all of the
      patients who survived, the contour of their reconstructed breast remained.

PMID- 22872843
TI  - Reducing donor site morbidity when reconstructing the nipple using a composite
      nipple graft.
AB  - BACKGROUND: Numerous procedures are available for nipple reconstruction without a
      single gold standard. This study presents a method for reducing donor-site
      morbidity in nipple reconstruction using a composite nipple graft after
      transverse rectus abdominis musculocutaneous flap breast reconstruction. METHODS:
      Thirty-five patients who underwent nipple reconstruction using a composite nipple
      graft technique between July of 2001 and December of 2009 were enrolled in this
      study. To reduce the donor site morbidity, the superior or superior-medial half
      dome harvesting technique was applied preserving the lateral cutaneous branch of
      the fourth intercostal nerves. The patients were asked to complete a previously
      validated survey to rate the color and projection of both nipples, along with the
      sensation and contractility of the donor nipple; and whether, in retrospect, they
      would undergo the procedure again. To compare projection, we performed a
      retrospective chart review of all the identifiable patients who underwent nipple
      reconstruction using the modified top hat flap technique by the same surgeon and
      during the same period. RESULTS: Thirty-five patients were identified who
      underwent nipple reconstruction using a composite nipple graft. Of those, 29
      patients (82.9%) responded to the survey. Overall, we received favorable
      responses to the donor site morbidity. Projection at postoperative 6 months and 1
      year was compared with the immediate postoperative results, as well as with the
      results of nipples reconstructed using the modified top hat flap. CONCLUSIONS:
      The technique used to harvest donor tissue is important. Preserving innervation
      of the nipple while harvesting can reduce donor site morbidity.

PMID- 22872844
TI  - The etiology and treatment of the softened phallus after the radial forearm
      osteocutaneous free flap phalloplasty.
AB  - BACKGROUND: The radial forearm osteocutaneous free flap is considered to be the
      standard technique for penile construction. One year after their operation, most
      patients experience a softened phallus, so that they suffer from difficulties in
      sexual intercourse. In this report, we present our experience with phalloplasty
      by radial forearm osteocutaneous free flap, as well as an evaluation of the
      etiology and treatment of the softened phallus. METHODS: Between March 2005 and
      February 2010, 58 patients underwent phalloplasty by radial forearm
      osteocutaneous free flap. Most of their neophallus had been softened subjectively
      and among them, 12 patients who wanted correction were investigated. We performed
      repetitive fat injection, artificial dermis grafting, silicone rod insertion, and
      rib bone with cartilaginous tip graft. Physical examination, plain radiograph,
      computed tomography, bone scintigraphy, and satisfaction scores were
      investigated. RESULTS: Most of the participants' penises have been softened after
      phalloplasty, and the skin elasticity had been also decreased. On plain
      radiograph, the distal end of the bone was self-rounded; however, the bone shape
      of the neophallus had no significant interval changes or resorption. Computed
      tomography showed equivocal density of cortical bone. On bone scintigraphy, the
      bone metabolism was active at 3 months postoperatively, and remained active 9
      years postoperatively. CONCLUSIONS: The use of a rib bone with cartilaginous tip
      graft could be an option for improvement of the softened phallus. Silicon rod
      insertion is also worth considering for rigidity of the softened phallus.
      Decreased rigidity due to soft tissue atrophy could be alleviated with repeated
      fat injection and artificial dermis grafting.

PMID- 22872846
TI  - Treatment of fingertip amputation in adults by palmar pocketing of the amputated
      part.
AB  - BACKGROUND: First suggested by Brent in 1979, the pocket principle is an
      alternative method for patients for whom a microsurgical replantation is not
      feasible. We report the successful results of a modified palmar pocket method in
      adults. METHODS: Between 2004 and 2008, we treated 10 patients by
      nonmicrosurgical replantation using palmar pocketing. All patients were adults
      who sustained a complete fingertip amputation from the tip to lunula in a digits.
      In all of these patients, the amputation occurred due to a crush or avulsion-type
      injury, and a microsurgical replantation was not feasible. We used the palmar
      pocketing method following a composite graft in these patients and prepared the
      pocket in the subcutaneous layer of the ipsilateral palm. RESULTS: Of a total of
      10 cases, nine had complete survival of the replantation and one had 20% partial
      necrosis. All of the cases were managed to conserve the fingernails, which led to
      acceptable cosmetic results. CONCLUSIONS: A composite graft and palmar pocketing
      in adult cases of fingertip injury constitute a simple, reliable operation for
      digital amputation extending from the tip to the lunula. These methods had
      satisfactory results.

PMID- 22872845
TI  - Flexor tenorrhaphy using absorbable suture materials.
AB  - BACKGROUND: Nonabsorbable sutures are favorable for repairing flexor tendons.
      However, absorbable sutures have performed favorably in an animal model. METHODS:
      Two-strand sutures using the interlocking modified Kessler method with
      polydioxanone absorbable sutures 4-0 were used to repair completely ruptured
      flexor tendons in 55 fingers from 41 consecutive patients. The medical records of
      average 42 follow up weeks were analyzed retrospectively. The data analyzed using
      the chi-squared test, and Fisher's exact test was used for postoperative
      complications. The results were compared with those of other studies. RESULTS:
      Among the index, middle, ring, and little fingers were injured in 9, 17, 16, and
      13 fingers, respectively. The injury levels varied from zone 1 to 5. Of the 55
      digits in our study, there were 26 (47%) isolated flexor digitorum profundus
      (FDP) injuries and 29 (53%) combined FDP and with flexor digitorum superficialis
      injuries. Pulley repair was also conducted. Concomitant injuries of blood vessels
      and nerves were found in 17 patients (23 fingers); nerve injuries occurred in 5
      patients (10 fingers). Two patients had ruptures (3.6%), and one patient had two
      adhesions (3.6%). Using the original Strickland criteria, all the patients were
      assessed to be excellent or good. Also, fibrosis and long-term foreign body
      tissue reactions such as stitch granuloma were less likely occurred in our study.
      Compared to the Cullen's report that used nonabsorbable sutures, there was no
      significant difference in the rupture or adhesion rates. CONCLUSIONS: Therefore,
      this study suggests that appropriate absorbable core sutures can be used safely
      for flexor tendon repairs.

PMID- 22872847
TI  - A retrospective review of iatrogenic skin and soft tissue injuries.
AB  - BACKGROUND: Even though the quality of medical and surgical care has improved
      remarkably over time, iatrogenic injuries that require surgical treatment
      including injuries caused by cast and elastic bandage pressure, extravasation,
      and dopamine-induced ischemia still frequently occur. The goal of this study was
      to estimate the incidence and analyze the distribution of iatrogenic injuries
      referred to our department. METHODS: A retrospective clinical review was
      performed from April 2006 to November 2010. In total, 196 patients (116 females
      and 80 males) were referred to the plastic surgery department for the treatment
      of iatrogenic injuries. We analyzed the types and anatomic locations of
      iatrogenic complications, along with therapeutic results. RESULTS: An
      extravasation injury (65 cases, 37.4%) was the most common iatrogenic
      complication in our study sample, followed by splint-induced skin ulceration,
      dopamine-induced necrosis, prefabricated pneumatic walking brace-related wounds
      and elastic bandage-induced wounds. Among these, prefabricated pneumatic walking
      brace-related complication incidence increased the most during the 5-year study
      period. CONCLUSIONS: The awareness of the very common iatrogenic complications
      and its causes may allow physicians to reduce their occurrence and allow for
      earlier detection and referral to a plastic surgeon. We believe this is the first
      study to analyze iatrogenic complications referred to a plastic surgery
      department in a hospital unit.

PMID- 22872848
TI  - Reconstruction of a severely crushed leg with interpositional vessel grafts and
      latissimus dorsi flap.
AB  - We present a case of a near total amputation at the distal tibial level, in which
      the patient emphatically wanted to save the leg. The anterior and posterior
      tibial nerves were intact, indicating a high possibility of sensory recovery
      after revascularization. The patient had open fractures at the tibia and fibula,
      but no bone shortening was performed. The posterior tibial vessels were
      reconstructed with an interposition saphenous vein graft from the contralateral
      side and a usable anterior tibial artery graft from the undamaged ipsilateral
      distal portions. The skin and soft tissue defects were covered using a
      subatmospheric pressure system for demarcating the wound, and a latissimus dorsi
      myocutaneous free flap for definite coverage of the wound. At 6 months after
      surgery, the patient was ambulatory without requiring additional procedures.
      Replantation without bone shortening, with use of vessel grafts and temporary
      coverage of the wound with subatmospheric pressure dressings before definite
      coverage, can shorten recovery time.

PMID- 22872849
TI  - Alternative Treatment of Osteoma Using an Endoscopic Holmium-YAG Laser.
AB  - Osteoma is one of the most common tumors of the cranial vault and the facial
      skeleton. For osteoma in the facial region, endoscopic resection is widely used
      to prevent surgical scarring. Tumors in a total of 14 patients were resected
      using an endoscopic holmium-doped yttrium aluminium garnet (Ho:YAG) laser with a
      long flexible fiber. Aside from having the advantage of not leaving a scar due to
      the use of endoscopy, this procedure allowed resection at any position, was
      minimally invasive, and caused less postoperative pain. This method yielded
      excellent cosmetic results, so the endoscopic Ho:YAG laser is expected to emerge
      as a good treatment option for osteoma.

PMID- 22872850
TI  - The Surgical Release of Dupuytren's Contracture Using Multiple Transverse
      Incisions.
AB  - Dupuytren's contracture is a condition commonly encountered by hand surgeons,
      although it is rare in the Asian population. Various surgical procedures for
      Dupuytren's contracture have been reported, and the outcomes vary according to
      the treatment modalities. We report the treatment results of segmental
      fasciectomies with multiple transverse incisions for patients with Dupuytren's
      contracture. The cases of seven patients who underwent multiple segmental
      fasciectomies with multiple transverse incisions for Dupuytren's contracture from
      2006 to 2011 were reviewed retrospectively. Multiple transverse incisions to the
      severe contracture sites were performed initially, and additional incisions to
      the metacarpophalangeal (MCP) joints, and the proximal interphalangeal (PIP)
      joints were performed if necessary. Segmental fasciectomies by removing the
      fibromatous nodules or cords between the incision lines were performed and the
      wound margins were approximated. The mean range of motion of the involved MCP
      joints and PIP joints was fully recovered. During the follow-up periods, there
      was no evidence of recurrence or progression of disease. Multiple transverse
      incisions for Dupuytren's contracture are technically challenging, and require a
      high skill level of hand surgeons. However, we achieved excellent correction of
      contractures with no associated complications. Therefore, segmental fasciectomies
      with multiple transverse incisions can be a good treatment option for Dupuytren's
      contracture.

PMID- 22872851
TI  - Sebaceous carcinoma arising from the nevus sebaceous.

PMID- 22872852
TI  - Differences in blood loss according to hemostatic method in the excision of giant
      neurofibroma.

PMID- 22872853
TI  - Bilateral circular xanthelasma palpebrarum.

PMID- 22872854
TI  - Treatment of congenital divided nevus of the eyelid with excision and
      blepharoplasty.

PMID- 22872855
TI  - Desmoid tumor of the rectus abdominis muscle in a postpartum patient.

PMID- 22872857
TI  - Access to journals through peer reviewers.

PMID- 22872858
TI  - Children with enuresis.

PMID- 22872861
TI  - PNAS Plus: Refining a successful experiment.

PMID- 22872859
TI  - Five friends of methylated chromatin target of protein-arginine
      methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to
      desumoylation.
AB  - Chromatin target of Prmt1 (Chtop) is a vertebrate-specific chromatin-bound
      protein that plays an important role in transcriptional regulation. As its
      mechanism of action remains unclear, we identified Chtop-interacting proteins
      using a biotinylation-proteomics approach. Here we describe the identification
      and initial characterization of Five Friends of Methylated Chtop (5FMC). 5FMC is
      a nuclear complex that can only be recruited by Chtop when the latter is arginine
      methylated by Prmt1. It consists of the co-activator Pelp1, the Sumo-specific
      protease Senp3, Wdr18, Tex10, and Las1L. Pelp1 functions as the core of 5FMC, as
      the other components become unstable in the absence of Pelp1. We show that
      recruitment of 5FMC to Zbp-89, a zinc-finger transcription factor, affects its
      sumoylation status and transactivation potential. Collectively, our data provide
      a mechanistic link between arginine methylation and (de)sumoylation in the
      control of transcriptional activity.

PMID- 22872860
TI  - Prolonged persistence of measles virus RNA is characteristic of primary infection
      dynamics.
AB  - Measles virus (MeV) is the poster child for acute infection followed by lifelong
      immunity. However, recent work shows the presence of MeV RNA in multiple sites
      for up to 3 mo after infection in a proportion of infected children. Here, we use
      experimental infection of rhesus macaques to show that prolonged RNA presence is
      characteristic of primary infection. We found that viral RNA persisted in the
      blood, respiratory tract, or lymph nodes four to five times longer than the
      infectious virus and that the clearance of MeV RNA from blood happened in three
      phases: rapid decline coincident with clearance of infectious virus, a rebound
      phase with increases up to 10-fold, and a phase of slow decrease to undetectable
      levels. To examine the effect of individual host immune factors on MeV load
      dynamics further, we developed a mathematical model that expressed viral
      replication and elimination in terms of the strength of MeV-specific T-cell
      responses, antibody responses, target cell limitations, and immunosuppressive
      activity of regulatory T cells. Based on the model, we demonstrate that viral
      dynamics, although initially regulated by T cells, require antibody to eliminate
      viral RNA. These results have profound consequences for our view of acute viral
      infections, the development of prolonged immunity, and, potentially, viral
      evolution.

PMID- 22872862
TI  - Atp6v0a4 knockout mouse is a model of distal renal tubular acidosis with hearing
      loss, with additional extrarenal phenotype.
AB  - Autosomal recessive distal renal tubular acidosis (dRTA) is a severe disorder of
      acid-base homeostasis, often accompanied by sensorineural deafness. We and others
      have previously shown that mutations in the tissue-restricted a4 and B1 subunits
      of the H(+)-ATPase underlie this syndrome. Here, we describe an Atp6v0a4 knockout
      mouse, which lacks the a4 subunit. Using beta-galactosidase as a reporter for the
      null gene, developmental a4 expression was detected in developing bone, nose,
      eye, and skin, in addition to that expected in kidney and inner ear. By the time
      of weaning, Atp6v0a4(-/-) mice demonstrated severe metabolic acidosis,
      hypokalemia, and early nephrocalcinosis. Null mice were hypocitraturic, but
      hypercalciuria was absent. They were severely hearing-impaired, as shown by
      elevated auditory brainstem response thresholds and absent endocochlear
      potential. They died rapidly unless alkalinized. If they survived weaning with
      alkali supplementation, treatment could later be withdrawn, but -/- animals
      remained acidotic with alkaline urine. They also had an impaired sense of smell.
      Heterozygous animals were biochemically normal until acid-challenged, when they
      became more acidotic than +/+ animals. This mouse model recapitulates the loss of
      H(+)-ATPase function seen in human disease and can provide additional insights
      into dRTA and the physiology of the a4 subunit.

PMID- 22872863
TI  - Structural basis for substrate recognition by a unique Legionella
      phosphoinositide phosphatase.
AB  - Legionella pneumophila is an opportunistic intracellular pathogen that causes
      sporadic and epidemic cases of Legionnaires' disease. Emerging data suggest that
      Legionella infection involves the subversion of host phosphoinositide (PI)
      metabolism. However, how this bacterium actively manipulates PI lipids to benefit
      its infection is still an enigma. Here, we report that the L. pneumophila
      virulence factor SidF is a phosphatidylinositol polyphosphate 3-phosphatase that
      specifically hydrolyzes the D3 phosphate of PI(3,4)P(2) and PI(3,4,5)P(3). This
      activity is necessary for anchoring of PI(4)P-binding effectors to bacterial
      phagosomes. Crystal structures of SidF and its complex with its substrate
      PI(3,4)P(2) reveal striking conformational rearrangement of residues at the
      catalytic site to form a cationic pocket that specifically accommodates the D4
      phosphate group of the substrate. Thus, our findings unveil a unique Legionella
      PI phosphatase essential for the establishment of lipid identity of bacterial
      phagosomes.

PMID- 22872864
TI  - Sacrificial nanofibrous composites provide instruction without impediment and
      enable functional tissue formation.
AB  - The fibrous tissues prevalent throughout the body possess an ordered structure
      that underlies their refined and robust mechanical properties. Engineered
      replacements will require recapitulation of this exquisite architecture in three
      dimensions. Aligned nanofibrous scaffolds can dictate cell and matrix
      organization; however, their widespread application has been hindered by poor
      cell infiltration due to the tight packing of fibers during fabrication. Here, we
      develop and validate an enabling technology in which tunable composite
      nanofibrous scaffolds are produced to provide instruction without impediment.
      Composites were formed containing two distinct fiber fractions: slow-degrading
      poly(epsilon-caprolactone) and water-soluble, sacrificial poly(ethylene oxide),
      which can be selectively removed to increase pore size. Increasing the initial
      fraction of sacrificial poly(ethylene oxide) fibers enhanced cell infiltration
      and improved matrix distribution. Despite the removal of >50% of the initial
      fibers, the remaining scaffold provided sufficient instruction to align cells and
      direct the formation of a highly organized ECM across multiple length scales,
      which in turn led to pronounced increases in the tensile properties of the
      engineered constructs (nearly matching native tissue). This approach transforms
      what is an interesting surface phenomenon (cells on top of nanofibrous mats) into
      a method by which functional, 3D tissues (>1 mm thick) can be formed, both in
      vitro and in vivo. As such, this work represents a marked advance in the
      engineering of load-bearing fibrous tissues, and will find widespread
      applications in regenerative medicine.

PMID- 22872865
TI  - Keap1 degradation by autophagy for the maintenance of redox homeostasis.
AB  - The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2)
      system is essential for cytoprotection against oxidative and electrophilic
      insults. Under unstressed conditions, Keap1 serves as an adaptor for ubiquitin E3
      ligase and promotes proteasomal degradation of Nrf2, but Nrf2 is stabilized when
      Keap1 is inactivated under oxidative/electrophilic stress conditions. Autophagy
      deficient mice show aberrant accumulation of p62, a multifunctional scaffold
      protein, and develop severe liver damage. The p62 accumulation disrupts the Keap1
      Nrf2 association and provokes Nrf2 stabilization and accumulation. However,
      individual contributions of p62 and Nrf2 to the autophagy-deficiency-driven liver
      pathogenesis have not been clarified. To examine whether Nrf2 caused the liver
      injury independent of p62, we crossed liver-specific Atg7::Keap1-Alb double
      mutant mice into p62- and Nrf2-null backgrounds. Although Atg7::Keap1-Alb::p62(-/
      ) triple-mutant mice displayed defective autophagy accompanied by the robust
      accumulation of Nrf2 and severe liver injury, Atg7::Keap1-Alb::Nrf2(-/-) triple
      mutant mice did not show any signs of such hepatocellular damage. Importantly, in
      this study we noticed that Keap1 accumulated in the Atg7- or p62-deficient mouse
      livers and the Keap1 level did not change by a proteasome inhibitor, indicating
      that the Keap1 protein is constitutively degraded through the autophagy pathway.
      This finding is in clear contrast to the Nrf2 degradation through the proteasome
      pathway. We also found that treatment of cells with tert-butylhydroquinone
      accelerated the Keap1 degradation. These results thus indicate that Nrf2
      accumulation is the dominant cause to provoke the liver damage in the autophagy
      deficient mice. The autophagy pathway maintains the integrity of the Keap1-Nrf2
      system for the normal liver function by governing the Keap1 turnover.

PMID- 22872866
TI  - Laminar analysis of visually evoked activity in the primary visual cortex.
AB  - Studying the laminar pattern of neural activity is crucial for understanding the
      processing of neural signals in the cerebral cortex. We measured neural
      population activity [multiunit spike activity (MUA) and local field potential,
      LFP] in Macaque primary visual cortex (V1) in response to drifting grating
      stimuli. Sustained visually driven MUA was at an approximately constant level
      across cortical depth in V1. However, sustained, visually driven, local field
      potential power, which was concentrated in the gamma-band (20-60 Hz), was
      greatest at the cortical depth corresponding to cortico-cortical output layers 2,
      3, and 4B. gamma-band power also tends to be more sustained in the output layers.
      Overall, cortico-cortical output layers accounted for 67% of total gamma-band
      activity in V1, whereas 56% of total spikes evoked by drifting gratings were from
      layers 2, 3, and 4B. The high-resolution layer specificity of gamma-band power,
      the laminar distribution of MUA and gamma-band activity, and their dynamics imply
      that neural activity in V1 is generated by laminar-specific mechanisms. In
      particular, visual responses of MUA and gamma-band activity in cortico-cortical
      output layers 2, 3, and 4B seem to be strongly influenced by laminar-specific
      recurrent circuitry and/or feedback.

PMID- 22872867
TI  - Task-switching costs promote the evolution of division of labor and shifts in
      individuality.
AB  - From microbes to humans, the success of many organisms is achieved by dividing
      tasks among specialized group members. The evolution of such division of labor
      strategies is an important aspect of the major transitions in evolution. As such,
      identifying specific evolutionary pressures that give rise to group-level
      division of labor has become a topic of major interest among biologists. To
      overcome the challenges associated with studying this topic in natural systems,
      we use actively evolving populations of digital organisms, which provide a unique
      perspective on the de novo evolution of division of labor in an open-ended
      system. We provide experimental results that address a fundamental question
      regarding these selective pressures: Does the ability to improve group efficiency
      through the reduction of task-switching costs promote the evolution of division
      of labor? Our results demonstrate that as task-switching costs rise, groups
      increasingly evolve division of labor strategies. We analyze the mechanisms by
      which organisms coordinate their roles and discover strategies with striking
      biological parallels, including communication, spatial patterning, and task
      partitioning behaviors. In many cases, under high task-switching costs,
      individuals cease to be able to perform tasks in isolation, instead requiring the
      context of other group members. The simultaneous loss of functionality at a lower
      level and emergence of new functionality at a higher level indicates that task
      switching costs may drive both the evolution of division of labor and also the
      loss of lower-level autonomy, which are both key components of major transitions
      in evolution.

PMID- 22872868
TI  - Essential anaplerotic role for the energy-converting hydrogenase Eha in
      hydrogenotrophic methanogenesis.
AB  - Despite decades of study, electron flow and energy conservation in methanogenic
      Archaea are still not thoroughly understood. For methanogens without cytochromes,
      flavin-based electron bifurcation has been proposed as an essential energy
      conserving mechanism that couples exergonic and endergonic reactions of
      methanogenesis. However, an alternative hypothesis posits that the energy
      converting hydrogenase Eha provides a chemiosmosis-driven electron input to the
      endergonic reaction. In vivo evidence for both hypotheses is incomplete. By
      genetically eliminating all nonessential pathways of H(2) metabolism in the model
      methanogen Methanococcus maripaludis and using formate as an additional electron
      donor, we isolate electron flow for methanogenesis from flux through Eha. We find
      that Eha does not function stoichiometrically for methanogenesis, implying that
      electron bifurcation must operate in vivo. We show that Eha is nevertheless
      essential, and a substoichiometric requirement for H(2) suggests that its role is
      anaplerotic. Indeed, H(2) via Eha stimulates methanogenesis from formate when
      intermediates are not otherwise replenished. These results fit the model for
      electron bifurcation, which renders the methanogenic pathway cyclic, and as such
      requires the replenishment of intermediates. Defining a role for Eha and
      verifying electron bifurcation provide a complete model of methanogenesis where
      all necessary electron inputs are accounted for.

PMID- 22872869
TI  - An aggression-specific cell type in the anterior hypothalamus of finches.
AB  - The anterior hypothalamus (AH) is a major integrator of neural processes related
      to aggression and defense, but cell types in the AH that selectively promote
      aggression are unknown. We here show that aggression is promoted in a very
      selective and potent manner by dorsal AH neurons that produce vasoactive
      intestinal polypeptide (VIP). Fos activity in a territorial finch, the violet
      eared waxbill (Estrildidae: Uraeginthus granatina) is positively related to
      aggression in the dorsal AH, overlapping a population of VIP-producing neurons.
      VIP is known to promote territorial aggression in songbirds, and thus we used
      antisense oligonucleotides to selectively block AH VIP production in male and
      female waxbills. This manipulation virtually abolishes aggression, reducing the
      median number of displacements in a 3-min resident-intruder test from 38 in
      control subjects to 0 in antisense subjects. Notably, most antisense and control
      waxbills exhibit an agonistic response such as a threat or agonistic call within
      2 s of intrusion. Thus, antisense subjects clearly classify intruders as
      offensive, but fail to attack. Other social and anxiety-like behaviors are not
      affected and VIP cell numbers correlate positively with aggression, suggesting
      that these cells selectively titrate aggression. Additional experiments in the
      gregarious zebra finch (Estrildidae: Taeniopygia guttata) underscore this
      functional specificity. Colony-housed finches exhibit significant reductions in
      aggression (primarily nest defense) following AH VIP knockdown, but no effects
      are observed for social preferences, pair bonding, courtship, maintenance
      behaviors, or anxiety-like behaviors. To our knowledge, these findings represent
      a unique identification of an aggression-specific cell type in the brain.

PMID- 22872871
TI  - Selective measurement of anti-tTG antibodies in coeliac disease and IgA
      deficiency: an alternative pathway.
AB  - OBJECTIVE: To determine the ability of selective antibody testing to screen for
      coeliac disease in the presence of IgA deficiency and to define the sensitivity
      of a pathway using this method. METHOD: All IgA and IgG anti-tTG tests performed
      at our centre between January 2008 and December 2009, using the Immunocap 250
      analyser, were retrospectively reviewed. Positive results were correlated with
      histology. Results were used to validate our diagnostic pathway. RESULTS: 12 289
      consecutive serological tests were reviewed. IgA deficient patients gave either
      an 'error' reading or very low response on the Immunocap 250 analyser. Subsequent
      testing of this sub-group demonstrated raised IgG anti-tTG antibodies in those
      with histologically proven coeliac disease. CONCLUSIONS: Using our antibody
      screening pathway, which involves the selective use of IgG anti-tTG, sensitivity
      increased from 87% to 92% in those with IgA deficiency. Adoption of this pathway
      for coeliac screening would negate the routine screening of immunoglobulin
      levels, with resultant cost saving.

PMID- 22872870
TI  - Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of
      upper-airway specimens can misrepresent lung microbiota.
AB  - Recent work using culture-independent methods suggests that the lungs of cystic
      fibrosis (CF) patients harbor a vast array of bacteria not conventionally
      implicated in CF lung disease. However, sampling lung secretions in living
      subjects requires that expectorated specimens or collection devices pass through
      the oropharynx. Thus, contamination could confound results. Here, we compared
      culture-independent analyses of throat and sputum specimens to samples directly
      obtained from the lungs at the time of transplantation. We found that CF lungs
      with advanced disease contained relatively homogenous populations of typical CF
      pathogens. In contrast, upper-airway specimens from the same subjects contained
      higher levels of microbial diversity and organisms not typically considered CF
      pathogens. Furthermore, sputum exhibited day-to-day variation in the abundance of
      nontypical organisms, even in the absence of clinical changes. These findings
      suggest that oropharyngeal contamination could limit the accuracy of DNA-based
      measurements on upper-airway specimens. This work highlights the importance of
      sampling procedures for microbiome studies and suggests that methods that account
      for contamination are needed when DNA-based methods are used on clinical
      specimens.

PMID- 22872872
TI  - Living donor kidney paired donation  transplantation: experience as a founding 
      member center of the National Kidney  Registry.
AB  - Kidney paired donation (KPD) is a safe and effective means of transplantation for
      transplant candidates with willing but incompatible donors. We report our single
      center experience with KPD through participation in the National Kidney Registry.
      Patient demographics, transplant rates, and clinical outcomes including delayed
      graft function (DGF), rejection, and survival were analyzed. We also review
      strategies employed by our center to maximize living donor transplantation
      through KPD. We entered 44 incompatible donor/recipient pairs into KPD from
      9/2007 to 1/2011, enabling 50 transplants. Incompatibility was attributable to
      blood type (54.4%) and donor-specific sensitization (43.2%). Thirty-six
      candidates (81.8%) were transplanted after 157 d (median), enabling pre-emptive
      transplantation in eight patients. Fourteen candidates on the deceased donor
      waiting list also received transplants. More than 50% of kidneys were received
      from other transplant centers. DGF occurred in 6%; one-yr rejection rate was
      9.1%. One-yr patient and graft survival was 98.0% and 94.8%. KPD involving
      participation of multiple transplant centers can provide opportunities for
      transplantation, with potential to expand the donor pool, minimize waiting times,
      and enable pre-emptive transplantation. Our experience demonstrates promising
      short-term outcomes; however, longer follow-up is needed to assess the impact of
      KPD on the shortage of organs available for transplantation.

PMID- 22872873
TI  - Abstracts of the 2011 ASCP Annual Meeting/WASPaLM XXVI World Congress. October 20
      22, 2012. Las Vegas, Nevada, USA.

PMID- 22872874
TI  - Retraction statement: When failure feels better than success: self-salience, self
      consistency, and affect.

PMID- 22872875
TI  - Abstracts of the Ninth International Symposium on Functional Neuroreceptor
      Mapping of the Living Brain. August 9-11, 2012.

PMID- 22872876
TI  - Calibration suggestions.

PMID- 22872877
TI  - Frank Michio Yatsu, MD (1932-2012).

PMID- 22872878
TI  - Data is not 'meaningful' unless used to improve care.

PMID- 22872879
TI  - Vocational rehabilitation: how are we doing?

PMID- 22872880
TI  - Overuse, underuse, and valuable use. Asking "is this really necessary?" is always
      appropriate.

PMID- 22872881
TI  - What's at the heart of fainting?  Most fainting is not related to abnormal heart
      rhythms.

PMID- 22872882
TI  - Tales of two heart failures. Both "stiff" and "weak" types demand attention, but
      stiff hearts are trickier to treat.

PMID- 22872883
TI  - Blood clots: the good, the bad, and the deadly. Those arising from
      atherosclerosis and atrial fibrillation can be very dangerous.

PMID- 22872884
TI  - Gut microbes may affect heart disease risk.  But studies in rodents suggesting a
      link may not play out in people.

PMID- 22872885
TI  - No beef with beef if it's lean.

PMID- 22872886
TI  - Stroke risk rises in people who are depressed.

PMID- 22872887
TI  - Radiation for breast cancer linked to narrowed heart arteries.

PMID- 22872888
TI  - Ask the doctor.  I see in-store promotions for low-fat muffins almost everywhere.
      Is there such a thing as a heart-healthy muffin?

PMID- 22872889
TI  - Ask the doctor. I am 70 years old, and since I started taking testosterone to
      boost below-normal levels of that hormone, my LDL and HDL levels have dropped.
      What's the cholesterol-testosterone connection?

PMID- 22872890
TI  - Take the hassle out of taking warfarin. Less frequent testing or home monitoring
      may be options.

PMID- 22872891
TI  - Arm-to-arm variations in blood pressure may warrant attention.  A difference of
      10 or more points could signal peripheral artery disease.

PMID- 22872892
TI  - Exercise protects the heart when diabetes threatens.  Lower resting heart rate
      may mean lower risk of diabetes.

PMID- 22872893
TI  - Angina in the intestines mirrors what happens in the heart.  Clogged gut arteries
      can cause pain--and much worse.

PMID- 22872894
TI  - The wake-up-call heart attack.  Four lessons we can learn from nonfatal cardiac
      events.

PMID- 22872895
TI  - Heart attack risk soars soon after losing a loved one.

PMID- 22872896
TI  - Satisfaction with job, family, sex life, and self may help the heart.

PMID- 22872897
TI  - No more routine liver tests for statin users.

PMID- 22872898
TI  - Everyday foods are top sources of sodium.

PMID- 22872899
TI  - Hidden atrial fibrillation is a possible culprit in mystery strokes.

PMID- 22872900
TI  - Ask the doctor.  What's the current status of homocysteine as a risk factor for
      heart disease?

PMID- 22872901
TI  - Ask the doctor.  A few years ago, I switched from regular soda to diet soda--and
      lost 12 pounds.  My husband tells me diet soda is bad for me, but isn't it better
      than the sugary stuff?

PMID- 22872902
TI  - Dangers of peripheral arterial disease. Wider use of simple screening test
      encouraged, especially in women.

PMID- 22872903
TI  - Light weights as effective as heavier weights for strength training.  Lifting
      less weight more times, to the point of fatigue, is the trick, study says.

PMID- 22872904
TI  - Migraine prevention: techniques are available, but underutilized. New guidelines
      emphasize ways to reduce the number of migraine attacks.

PMID- 22872905
TI  - Breakthrough in dry version of macular degeneration.  Discovery of biological
      pathway may lead to cure for dry AMD.

PMID- 22872906
TI  - New implant coating promotes bone growth. Nanoscale film enables a better seal
      between a patient's own bone and the implant, eliminating the need for revision
      surgery.

PMID- 22872907
TI  - I've had some odd physical symptoms lately, including muscle and joint pains,
      neck discomfort, hair falling out, depression and anxiety, fatigue, and
      unexplained weight gain.  My doctor suspects a possible thyroid condition and
      wants me to take some tests.  What can I expect?

PMID- 22872908
TI  - What are the latest developments in total hip replacement--materials, techniques,
      procedures?

PMID- 22872909
TI  - Stabilization of oxygen evolution and primary electron transport reactions in
      photosystem II against heat stress with glycinebetaine and sucrose.
AB  - The protective action of co-solutes, such as sucrose and glycinebetaine, against
      the thermal inactivation of photosystem II function was studied in untreated and
      Mn-depleted photosystem II preparations. It was shown that, in addition to the
      reactions that depend on the oxygen evolving activity of the photosystem, those
      that implicate more intimately the reaction center itself are protected by high
      concentrations of osmolytes. However, the temperature required to inhibit oxygen
      evolution totally in the presence of osmolytes is lower than that required to
      eliminate reactions, such as P680 (primary electron donor in photosystem II)
      photo-oxidation and pheophytin photo reduetion, which only involve charge
      separation and primary electron transport processes. The energy storage measured
      from the thermal dissipation yield during photoacoustic experiments and the yield
      of variable fluorescence are also protected to a significant degree (up to 30%)
      at temperatures at which oxygen evolution is totally inhibited. It is suggested
      that a cyclic electron transport reaction around photosystem II may be preserved
      under these conditions and may be responsible for the energy storage measured at
      relatively high temperatures. This interpretation is also supported by
      thermoluminescence data involving the recombination between reduced electron
      acceptors and oxidized electron donors at - 30 and - 55  degrees C. The data also
      imply that a high concentration of osmolyte allows the stabilization of the
      photosystem core complex together with the oxygen-evolving complex. The
      stabilization effect is understood in terms of the minimization of protein-water
      interactions as proposed by the theory of Arakawa and Timasheff (Biophys. J., 47
      (1985) 411--414).

PMID- 22872910
TI  - Effect of extraction and re-addition of manganese on light reactions of
      photosystem- II preparations.

PMID- 22872911
TI  - In photoinhibited photosystem II particles pheophytin photoreduction remains
      unimpaired.
AB  - Oxygen-evolving photosystem II particles (DT 20) isolated from pea chloroplasts
      by digitonin-Triton X-100 fractionation were photoinhibited with 150 W. m(-2)
      white light, at 20 degrees C under three conditions: aerobic, anaerobic and
      strongly reducing (E(h) poised to approx. -250 mV with dithionite). Hill reaction
      rate (H (20) + BQ)and variable fluorescence (Fv) declined in parallel in all
      three cases with shortening half times: 30, 10 and 2.5 min, respectively. Light
      induced absorbance changes at 685 nm characteristic of reversible photo
      accumulation of reduced pheophytin (& z -2.50 mV) remained essentially unchanged.
      We conclude that the three types of photoinhibitory treatment do not impair the
      separation of charges between chlorophyll P-680 and pheophytin in the photosystem
      II reaction center.

PMID- 22872912
TI  - Hydrogen evolution by subchloroplast preparations of photosystem II from pea and
      spinach,.
AB  - Hydrogen (H,) evolution rates were measured by the gas chromatographic technique
      upon illumination of different subchloroplast preparations of higher plants
      without exogenous hydrogenase under anaerobic conditions. Subchloroplast
      preparations enriched in photosystem II (PS II) in the presence of an electron
      donor TMPD (N,N,N,W-tetramethyl-p-phenylenediamine)are shown to have higher Hz
      evolution rates (up to 30 nmol/mg Chl per h) than preparations enriched in PS I
      under the same conditions. The data on the suppression of & evolution by well
      known inhibitors of PS II (dinoseb,atrazine) prove that the Hz photoproduction is
      sensitized by PS II reaction centers.

PMID- 22872913
TI  - Epigenome enhancer profiling reveals signature for colon cancer.

PMID- 22872914
TI  - New sequencing technique produces high-resolution map of 5-hydroxymethylcytosine.

PMID- 22872915
TI  - [Effect of extraction and subsequent addition of manganese ions on photooxidation
      of chlorophyll P(680) in the photosystem II preparations].
AB  - Effect of reversible removal of Mn on the amplitude of photoinduced absorbance
      changes (DeltaA) related to photooxidation of chlorophyll P(680) in pea oxygen --
      evolving photosystem 2 (PS(2)) preparations has been studies. It is shown that
      after complete removal of Mn the amplitude of DeltaA is increased by a factor of
      7--8 and it is decreased again to the initial value upon subsequent addition of
      MnCl(2). This reactivation needs four Mn atoms per one reaction centre (RC) of
      PS(2). In the presence of 3 MUM MgCI(2) the reactivation requires two Mn atoms
      per RC of PS2. The obtained data confirm our earlier conclusion that a four
      atomic Mn centre functions in the donor side of PS(2); two of them can be
      replaced by either Mg(2+) or other divalent metals.

PMID- 22872916
TI  - Does the proliferation of human lymphoma cells depend on the mutation of EZH2 and
      consequential epigenetic modification of H3K27?

PMID- 22872917
TI  - Role of epigenetic modifications of SOX 9 in gastric carcinoma.

PMID- 22872918
TI  - Is there a decrease in Keap1 RNA expression in colorectal cancer cells, and is
      this decrease in expression due to hypermethylation?

PMID- 22872919
TI  - [Effect of quercetin on electron transfer in photosystems I and II of pea
      chloroplasts].
AB  - The effect of such flavonoid as quercetin and its oxidized from on electron
      transfer was studied in subchloroplast preparations of the Photosystem II (PS(2)
      and Photosystem I (PS(1)). Quercetin and its oxidized form are shown to inhibit
      the electron transfer in the PS(2) acceptor and donor sites, respectively. They
      also function as an electron donor or and electron acceptor in PS(1)),
      respectively

PMID- 22872920
TI  - Puzzles in practice. Idiopathic orbital inflammatory syndrome (IOIS).

PMID- 22872921
TI  - Neurology symposium. A joint RCPE and RCGP symposium held on 16 November 2011 at
      the Royal College of Physicians of Edinburgh.

PMID- 22872922
TI  - Care of the elderly symposium. A symposium held on 30 March 2012 at the Royal
      College of Physicians of Edinburgh.

PMID- 22872923
TI  - James Hamilton, the younger (1767-1839).

PMID- 22872924
TI  - Respiratory medicine symposium. A symposium held on 14 March 2012 at the Royal
      College of Physicians of Edinburgh.

PMID- 22872926
TI  - Notice of Duplicate Publication: Renal epithelial neoplasms: diagnostic
      applications of gene expression profiling.

PMID- 22872925
TI  - Struggling trainees symposium. A joint Royal College of Physicians of Edinburgh
      and Royal College of Practioners symposium held on 9 December 2011 at the RCPE.

PMID- 22872927
TI  - Comparison of bacterial identification by MALDI-TOF mass spectrometry and
      conventional diagnostic microbiology methods: agreement, speed and cost
      implications.
AB  - Identification of microbial pathogens still relies primarily on culture and
      phenotypic methods, which is labour-intensive and time-consuming. In this study,
      identification of bacteria with valid standard identification using BD Phoenix,
      API panels and other recommended procedures is compared to identification with
      matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass
      spectrometry using the MALDI Biotyper (Bruker Daltonics) in the setting of a
      routine NHS diagnostic microbiology laboratory. In total, 928 bacterial isolates
      obtained from blood (n=463), wounds and pus (n=208), respiratory tract (n=100),
      faeces (n=86) and urines (n=71) were analysed. There were 721 (77.7%) isolates
      with a MALDI Biotyper score > or =2.0, indicating secure genus and probable
      species identification; and 149 (16.1%) isolates with a score > or =1.7 and <2.0
      indicating probable genus identification. The isolates with scores of > or =2.0
      and > or =1.7 comprised 31 and 33 genera and 65 and 67 species, respectively.
      Overall, 99.4% and 99.1% of organism identifications were in agreement between
      the MALDI Biotyper and conventional identification at the genus level, and 89.3%
      and 87.8% at species level when analysing organisms with MALDI Biotyper scores >
      or =2.0 and > or =1.7, respectively. With many but not all organisms,
      identification at the genus level is sufficient; however, MALDI Biotyper
      separation of 208 staphylococci into Staphylococcus aureus and coagulase-negative
      staphylococci was always correct when scores were > or =1.7. First results were
      obtained after 5-10 min and analysis of a full 96-well target plate was completed
      in approximately 90 min. Substantial savings of between pounds 1.79 and pounds
      2.56 per isolate, depending on the cost model of acquisition of the MALDI
      Biotyper system and number of isolates tested, would be realised when all 928
      isolates were identified using the MALDI Biotyper and disk-susceptibility testing
      when compared to the cost for 618 Phoenix ID panels and 158 API panels and disk
      susceptibility tests only (i.e., not taking into account costs incurred for
      identification of the remaining 152 mixed isolates). Microbial identification by
      MALDI Biotyper offers a rare opportunity for significant cost-neutral or even
      cost-saving quality improvements in medical diagnostics.

PMID- 22872928
TI  - Dermatofibrosarcoma protuberans: dealing with slow Mohs procedures employing
      formalin-fixed, paraffin wax-embedded tissue in a busy diagnostic laboratory.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a relatively uncommon tumour that
      arises in the dermis and underlying soft tissue. Surgical removal is the
      preferred treatment, with relatively wide clearance margins of 3 cm or more. Slow
      Mohs procedures are often employed successfully to treat patients with such
      tumours. Slow Mohs procedures offer the benefit of improved cure rates and
      maximal tissue conservation. However, dealing with such tissue successfully
      presents the laboratory with a host of technical problems. This report advocates
      a set protocol to follow for slow Mohs, based on the experience acquired from
      dealing with 37 cases of DFSP over a 12-year period. The report establishes the
      benefits of slow Mohs paraffin wax-embedded tissue over frozen sections in terms
      of improved morphology, tissue preservation and immunocytochemical labelling with
      anti-CD34.

PMID- 22872929
TI  - Bmi-1 siRNA inhibited ovarian cancer cell line growth and decreased telomerase
      activity.
AB  - The knockdown of Bmi-1 could effectively suppress cancer cell proliferation and
      tumourigenicity in several cancers. This study aims to investigate whether or not
      Bmi-1 plays a causative role in the proliferation of ovarian epithelial cancer
      cells and telomerase activity. The messenger RNA (mRNA) and protein expression
      levels of Bmi-1 in the human ovarian carcinoma cell line OVCAR-3 were
      downregulated by Bmi-1 siRNA, as confirmed by real-time polymerase chain reaction
      (PCR) and Western blot. Cell viability was analysed by MTT assay, and telomerase
      activity was analysed by a modified telomeric repeat amplification protocol.
      Targeting Bmi-1 with siRNA inhibited Bmi-1 mRNA over five-fold compared with the
      control cells, and inhibited Bmi-1 protein expression over three-fold compared
      with control cells. The viability of the OVCAR-3 ovarian cancer cell line was
      reduced by Bmi-1 mRNA compared to control cells. Telomerase activity was
      decreased 22.73% (from 0.33 to 0.255) by Bmi-1 siRNA treatment compared to
      control cells. As Bmi-1 siRNA depressed telomerase activity, cell immortalisation
      may be prevented; thus, silencing Bmi-1 may be a potential therapy to manage
      ovarian cancer.

PMID- 22872930
TI  - Incomplete filling of lithium heparin tubes affects the activity of creatine
      kinase and gamma-glutamyltransferase.
AB  - This study aims to assess whether or not incomplete filling of primary lithium
      heparin tubes may influence the activity of creatine kinase (CK), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and gamma
      glutamyltransferase (GGT). Blood was drawn from 20 healthy volunteer using an
      identical sequence of tubes. First, a 6 mL, 13 x 100 mm 14 unit/mL lithium
      heparin Vacuette was filled and discharged. Then, three identical lithium heparin
      Vacuette tubes were filled, one to the nominal volume (i.e., full-draw tube),
      another with half of the nominal volume (half-draw tube) and the last with one
      third of the nominal volume (low-draw tube). The plasma was separated and tested
      for CK (non-activated by N-acetylcysteine), AST and ALT on a Beckman Coulter
      Unicel DxC 800. Tests for CK were performed with a different reagent on a Beckman
      Coulter AU5800 (activated by N-acetylcysteine). Although the concentrations of
      ASL and ALT measured on the Unicel DxC and that of CK measured on the AU5800 did
      not change significantly across the different specimens, those of CK and GGT
      measured on the Unicel DxC 800 were significantly increased in the half-draw and
      low-draw tubes. The percentage bias of CK on the Unicel DxC 800 (using Bland
      Altman plots) was 3.3% and 7.9% for the half-draw and low-draw tubes,
      respectively, whereas that of GGT was 10.3% and 16.6% for the half-draw and low
      draw tubes, respectively. These results suggest that short-draw lithium heparin
      tubes might be unsuitable for testing GGT and CK using specific combinations of
      reagents and instrumentation.

PMID- 22872931
TI  - Quantification of tumour and circulating vascular endothelial growth factor
      (VEGF) in patients with oesophagogastric cancer: a long-term follow-up study.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that
      regulates tumour angiogenesis. The prognostic significance of VEGF expression
      remains incompletely investigated for patients with oesophagogastric cancer. This
      study assesses the significance of tumour VEGF (T-VEGF) and circulating VEGF (C
      VEGF) expression in a 10-year follow-up of patients with oesophagogastric cancer.
      Patients undergoing surgical resection were prospectively recruited between
      February 1999 and August 2000. Circulating VEGF, derived both from plasma (P
      VEGF) and serum (S-VEGF), and T-VEGF were assessed using a commercial enzyme
      linked immunosorbent assay (ELISA). As platelet count may contribute to C-VEGF,
      pre-operative platelet levels were also recorded to exclude a confounding effect.
      Patients were followed up over a 10-year period using the Northern Ireland Cancer
      Registry. Sixty-one patients were recruited (men=45) with a mean age of 65.7
      years. The 10-year survival was 19.7% (n=12) with a median follow-up of 808 days
      (inter-quartile range [IQR]: 349.5-2358.5). Union for International Cancer
      Control (UICC) tumour staging was Stage I=9 (14.8%), Stage II=15 (24.6%), Stage
      III=33 (54.1%) and Stage IV=4 (6.6%). The only significant relationship between
      clinicopathological features and the study variables was for S-VEGF, which was
      elevated in patients with advanced T-stage (P = 0.05). Circulating VEGF did not
      correlate with platelet count. Although a trend towards decreased survival was
      observed for patients who had positive lymph nodes (P = 0.08) and advanced UICC
      stage (P = 0.09) on univariate analysis, only lymphovascular invasion
      significantly predicted poor prognosis in this cohort (P = 0.05). Therefore,
      ELISA quantification of circulatory or tumour VEGF does not appear to be a
      significant predictor of mortality in patients with oesophagogastric cancer.

PMID- 22872932
TI  - Mining the antibiogram: what more can it tell us?

PMID- 22872933
TI  - Hypoglycaemia due to autoimmune insulin syndrome in a 78-year-old Chinese man.

PMID- 22872934
TI  - A history of blood glucose meters and their role in self-monitoring of diabetes
      mellitus.
AB  - Self-monitoring blood glucose (SMBG) systems have the potential to play an
      important role in the management of diabetes and in the reduction of risk of
      serious secondary clinical complications. This review describes the transition
      from simple urine sugar screening tests to sophisticated meter and reagent strip
      systems to monitor blood glucose. Significant developments in design and
      technology over the past four decades are described since the first meter was
      introduced in 1970. Factors that have influenced this evolution and the
      challenges to improve analytical performance are discussed. Current issues in the
      role of SMBG from the clinical, patient and manufacturer perspectives, notably
      adherence, costs and regulations, are also considered.

PMID- 22872935
TI  - [Sharing information: between support and independence].

PMID- 22872936
TI  - [Acute and postherpetic neuralgia in the elderly: analysis of evidence for
      therapeutic options].
AB  - Initiated within the first 72 hours of the rash, the aim of antiviral drugs
      prescribing is to reduce both acute neuralgia (AN) and later complications and
      especially postherpetic neuralgia (PHN). However their analgesic as well as
      preventative effect on AN and PHN is modest. With the lack of the preventive
      vaccine in Switzerland and in the absence of more effective antiviral drugs,
      combinations with analgesic drugs are often needed in pain management. However
      medication selection and prescribed dosage in the context of old patients'
      frailty, co-morbidities and often polypharmacy must be carefully considered.
      Based on analysing the evidences from the literature, this review presents the
      therapeutic options we have at one's disposal and proposes a stepwise management
      for both AN and PHN specifically designed for aged population.

PMID- 22872937
TI  - [Spinal stenosis: diagnosis and treatment].
AB  - Spondylotic cervical myelopathy (SCM) is a radiologic entity that can match a
      clinical syndrome of varying degree of severity, and results from spinal canal
      narrowing due to physiological degeneration of the cervical spine. Clinically,
      cervical spinal canal narrowing can produce minimal symptoms such as non-specific
      neck pain, foraminal entrapment of nerve roots, or more severe, chronic
      myelopathy. SCM initially manifests by signs of posterior medullary tract
      dysfunction with subsequent pallesthesia, resulting in gait and balance
      disturbance. Spasticity due to lower motoneurone impairment and incontinence may
      appear in later stages. Once the symptoms of myelopathy occur, functional
      deterioration will take place sooner or later. Surgery can then be recommended
      and scheduled according to the severity of functional impairment and imaging.

PMID- 22872938
TI  - [Pain medication during pregnancy].
AB  - To treat pain that does not respond to non-pharmacological approaches in a
      pregnant woman represents a challenge for the primary care physician. He is often
      the first health professional to be consulted and finds himself confronted to not
      only one but two patients:the mother and the fetus. His knowledge on pain
      treatment and the practical approach that he is used to, will have to be adapted
      to this new equation. He will have to weigh the benefit for the mother against
      the risk for the fetus, while creating a true relationship with his patient.
      Although only a few drugs are considered compatible with pregnancy, the data
      available from the literature allow nowadays to better understand the nature of
      the risk when exposing the fetus to a given drug and to elaborate evidence-based
      recommendations.

PMID- 22872939
TI  - [Mindfulness-based therapeutic approaches: benefits for individuals suffering
      from pain].
AB  - Chronic diseases and their associated biopsychosocial adjustements tax the limits
      of modern conventional medicine, with the need then to turn towards new
      resources. Among these, Mindfulness-Based Stress Reduction (MBSR) is a
      therapeutic approach developed more than 30 years ago. Designed as an adjuvant to
      medical care, in particular in the case of chronic pain which is the scope of our
      article, MBSR is usually provided in group format and based on a meditative
      practice. Simple, brief and cost-limited, MBSR can potentially be offered to a
      wide variety of chronic diseases and is part of participatory medicine. After
      having presented this approach, several results from studies confirming the
      legitimacy of MBSR as a nonreligious and nonesoteric scientific approach for the
      treatment of various diseases will be reported.

PMID- 22872940
TI  - [Hypnosis and pain: current and perspective knowledge].
AB  - After further controversies, the definition of hypnosis is to be at the same time
      a modified state of consciousness and a particular intersubjective relation
      between a practitioner and his patient. In a synthetic way, we can say that
      mechanisms of hypnosis on acute pain are now well known, and its efficiency is
      particularly proved in the pain provoked by the care. On the other hand, the
      knowledge concerning the action of the hypnosis on chronic pain is much more
      complex to understand. If the hypnosis allows connoting differently pain and to
      decrease its implication in patient's life, otherWise the long-term
      reorganizations of hypnosis on chronic pain are still for the study. In practice,
      the field which his particularly in development is the analogical processes of
      the speech, because they are particularly present in pain medicine, and easy to
      use in hypnotic method.

PMID- 22872941
TI  - [Somatization, migration and culture: common assumptions and alternative
      strategies].
AB  - This article wishes to deconstruct the stereotype of the "somatizing migrant" by
      reexamining the process of somatization in a cultural perspective and by pointing
      out the factors that may jeopardize the therapeutic relationship with a migrant
      patient. It offers suggestions to broaden the clinician's perspective of his
      patient, and argues for multiple interpretations of the somatization process.

PMID- 22872942
TI  - [Are non-invasive tests going to replace liver biopsy for diagnosis of liver
      fibrosis?].
AB  - Liver fibrosis is associated with chronic liver diseases, and may evolve into
      cirrhosis that may be complicated by liver failure and portal hypertension.
      Detection and quantification of liver fibrosis is a key point in the follow-up of
      patients with chronic liver diseases. Liver biopsy is the gold standard method to
      assess and quantify fibrosis, but its invasiveness is a limiting factor in
      everyday clinical practice. Non invasive markers using either biological or
      radiological parameters have been developed and may decrease the need for liver
      biopsy in some cases. However, information is limited to fibrosis, and cut-offs
      values and diagnostic accuracies for significant fibrosis may vary according to
      the etiology of liver disease. Liver biopsy allows the assessment of intermediate
      stages of fibrosis and describes accompanying lesions.

PMID- 22872943
TI  - [Trends in the treatment of spinal osteoporic fractures: vertebroplasty and
      kyphoplasty].
AB  - Vertebral osteoporotic fracture (VOF) is a major problem of public health.
      Surgical treatments such as vertebroplasty and kyphoplasty are interesting
      adjuvant treatments for the management of osteoporosis. A consensus proposed by
      the principal contributors of this management is important. Regarding the actual
      data, we propose a vertebroplasty or a kyphoplasty for all patients suffering of
      an acute VOF. If a previous kyphosis or an important local kyphosis exists,
      secondary to the acute VOF or others, we propose a kyphoplasty. If the VOF is
      older and the conservative treatment is inefficient, we propose a vertebroplasty.
      In all cases, a specific management and treatment of osteoporosis is proposed.

PMID- 22872944
TI  - [Is the health care debate falling on deaf ears?].

PMID- 22872945
TI  - [From eternity to assisted suicide].

PMID- 22872947
TI  - [Serotonin, discovered 60 years ago].

PMID- 22872949
TI  - [Denial of reality].

PMID- 22872948
TI  - [Diesel fumes are really carcinogenic].

PMID- 22872950
TI  - ACOs need to leverage I.T. to make good on their mission.

PMID- 22872951
TI  - ACOs: data sharing, data security.

PMID- 22872952
TI  - Plain speaking? Why HIT departments need to think about health literacy.

PMID- 22872953
TI  - Physician champion. Interview by Elizabeth Gardner.

PMID- 22872954
TI  - Four evolving strategies in the emergent treatment of acute ischemic stroke.
AB  - Stroke is the leading cause of long-term disability in the United States and is
      the fourth leading cause of death, affecting nearly 800,000 patients each year.
      The physical, emotional, and financial toll stroke inflicts on patients and their
      families cannot be overstated. At the forefront of acute stroke care, emergency
      clinicians are positioned to have a major impact on the quality of care that
      stroke patients receive. This issue outlines and reviews the literature on 4
      evolving strategies reflecting developing advancements in the care of acute
      ischemic stroke and their potential to impact patients in the emergency
      department setting: (1) the expanding window for intravenous rt-PA, (2) the use
      of multimodal computed tomographic scanning in emergent diagnostic imaging, (3)
      endovascular therapies for stroke, and (4) stroke systems of care. Whether
      practicing in a tertiary care environment or in a remote emergency department,
      emergency clinicians will benefit from familiarizing themselves with these
      advancements and should consider how these new approaches might influence their
      management of patients with acute ischemic stroke.

PMID- 22872955
TI  - A year of accomplishments.

PMID- 22872956
TI  - Times are changing.

PMID- 22872957
TI  - Pain treatment creating pain.

PMID- 22872958
TI  - Increasing prevalence of anterior cruciate ligament injuries in a collegiate
      population.
AB  - OBJECTIVE: To detect a possible increasing trend in the annual prevalence of
      anterior cruciate ligament (ACL) injuries in a collegiate population and whether
      gender, sport, or year of the participant was predictive of a prior ACL injury.
      DESIGN: Retrospective case series SETTING: West Virginia University.
      PARTICIPANTS: Review of 3079 physical examination forms for prior ACL injury in
      athletes presenting for collegiate participation from 1996-2008. MAIN OUTCOME
      MEASURES: Presence or absence of ACL injury at presentation for preparticipation
      physical examination. RESULTS: There was a slight increase in the annual
      prevalence of ACL injuries over the study period. Gender and sport of the
      participant were not predictive of a prior ACL injury. CONCLUSIONS: Prevalence of
      ACL injuries increased over time in the population. Further research is needed to
      determine if this result is reflective of a growing national trend in athletes
      with a prior ACL injury presenting for collegiate participation.

PMID- 22872959
TI  - An unusual form of listerial CNS infection.
AB  - Listeria monocytogenes is a known cause of meningitis, but cerebral abscess
      formation is exceedingly rare. We describe a patient who presented with an
      unsteady gait and a small ring-enhancing lesion in the right parietal lobe.
      Pathologic evaluation demonstrated an abscess with associated microglial nodules,
      and culture revealed Listeria. In spite of the rarity of this entity,
      immunosuppression has been noted to be a predisposing factor. Our patient had
      diabetes mellitus and chronic obstructive pulmonary disease with recent
      prednisone administration, both very common ailments in the population of West
      Virginia.

PMID- 22872960
TI  - Atypical presentation of frontotemporal dementia masquerading as bipolar disorder
      and substance abuse: a case report.
AB  - This is the case of a 44-year-old man with frontotemporal lobar dementia whose
      presentation was consistent with bipolar affective disorder with psychosis in
      addition to ongoing substance abuse. Despite extended periods of sobriety and
      multiple medications to target Bipolar Disorder, his symptoms remained
      refractory. With repeated brain imaging and progression of the disease,
      frontotemporal dementia was diagnosed. The patient went on to develop amyotrophic
      lateral sclerosis (ALS), which is known to overlap the neuropathological features
      with frontotemporal lobar dementia. Respiratory compromise ultimately led to this
      patient's death, which was deemed secondary to ALS. This case demonstrates the
      need for clinicians to recognize differential diagnoses in manic and psychotic
      symptoms resistant to polypharmacy.

PMID- 22872961
TI  - Automated external defibrillators in West Virginia schools.
AB  - INTRODUCTION: Sudden death, particularly when occurring in children and
      adolescents, is a traumatic event not only for the victim's family, but for the
      entire community. It has been shown that school-based automated external
      defibrillator (AED) programs provide a high survival rate for both students and
      nonstudents who suffer sudden cardiac arrest (SCA) on school grounds. The use of
      AEDs is becoming increasingly more common in schools in the United States. In
      West Virginia middle and high schools, we analyzed the prevalence and use of
      AEDs, barriers to obtaining a device, and cases of sudden death on school
      grounds. METHODS: A mailed survey distributed to West Virginia high schools and
      middle schools collected general demographic data, AED data, and occurrences of
      sudden death on school grounds. Schools reporting a death were contacted to
      obtain details regarding the event. For schools with a device, the number of
      AEDs, length of possession, reasons for and means of obtaining the AED, personnel
      trained to operate the AED and the number of device uses were determined. For
      schools without an AED, barriers to and interest in obtaining a device were
      determined. RESULTS: Two hundred and twenty-five of 312 surveys (72%) were
      returned. One hundred and fifty-two schools (68%) currently have at least one AED
      and 73 schools (32%) do not have an AED. Public high schools had the highest
      prevalence of AEDs (76%) compared to public middle schools (62%) and private
      schools (67%). Sixty-nine percent of schools obtained their devices by donations
      or grants and 32% obtained them using school funds. Barriers to obtaining a
      device included cost (82%), lack of trained personnel (45%), unfamiliarity with
      AED (22%), and liability issues (19%). There were a total of 23 deaths on school
      premises reported by 20 schools. There was one reported occurrence of an AED
      being used to save a life. CONCLUSION: Over two thirds of West Virginia middle
      schools and high schools currently have at least one AED on their premises. An
      AED is an effective way of preventing death following sudden cardiac arrest, and
      has saved at least one life in a West Virginia school. While most schools without
      AEDs cite cost as the main deterrent, the majority of schools with a device
      received them via donation or grant. We submit that a number of sudden deaths on
      West Virginia school grounds could possibly have been averted by use of an AED.

PMID- 22872962
TI  - Hemangioma of the scrotal septum: a rare entity in infants with review of the
      literature.
AB  - Hemagiomas are most common tumors in infancy; however, scrotal septum hemangiomas
      are very rare with only 45 cases reported in the literature. We report a case of
      a 6-month-old child who presented with a scrotal mass at birth which had
      increased in size with age. A scrotal ultrasound with color doppler analysis,
      revealed a soft tissue mass with diffusely increased blood flow. Scrotal mass
      excision was performed and the pathology confirmed a capillary hemangioma.

PMID- 22872963
TI  - Smoking during pregnancy: a retrospective analysis of West Virginia adolescents.

PMID- 22872964
TI  - Business and bylaws.

PMID- 22872965
TI  - MAG's strength.

PMID- 22872966
TI  - MAG alliance offering up its support for medicine.

PMID- 22872967
TI  - MagMutual: reflecting on 30 years, and thanking MAG for its key role.

PMID- 22872968
TI  - Physicians and social media: a brave new world.

PMID- 22872969
TI  - The state of broadband in Georgia.

PMID- 22872970
TI  - Obtaining medical literature in an information-rich world.

PMID- 22872971
TI  - Georgia's plan for health IT: help you do what you do best.

PMID- 22872972
TI  - Does religion affect medical students' attitudes toward ethical dilemmas?

PMID- 22872973
TI  - When penny wise becomes pound foolish.

PMID- 22872975
TI  - Retention of physician office medical records.

PMID- 22872974
TI  - A top health technology hazard: contamination from endoscopes.

PMID- 22872977
TI  - What a country.

PMID- 22872976
TI  - Bylaws are more important than ever.

PMID- 22872978
TI  - Improved clinicopathologic assessments of acute liver damage due to trauma in
      Indian ring-necked parakeets (Psittacula krameri manillensis).
AB  - Increased activities of certain biochemical enzymes (alanine aminotransferase
      [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], alkaline
      phosphatase [ALP]) have been associated with blunt liver injury in many species.
      To evaluate changes in plasma hepatic biochemical parameters in acute avian liver
      disease caused by trauma and to compare biochemical changes with histologic
      lesions in hepatic parenchyma, 30 healthy fasted Indian ring-necked parakeets
      (Psittacula krameri manillensis) were divided into 2 groups, and traumatic liver
      injury was caused by endoscopic liver biopsy (group 1) or by liver biopsy and
      crushing injury to the hepatic parenchyma with endoscopic forceps (group 2) in
      anesthetized birds. Blood samples were collected at baseline and at 12, 24, 36,
      48, 60, 72, 84, 96, 108, and 120 hours in alternate groups to compare analyte
      values after injury with those at baseline. Results showed consistently decreased
      plasma ALP activity (excluding 1 time point) throughout the study, which was
      thought to be associated with isoflurane administration. Plasma glutamate
      dehydrogenase activity initially increased but rapidly declined thereafter and
      was attributed to acute focal hepatocellular injury. In both groups, increases in
      plasma AST, ALT, and LDH activities was most likely caused by muscle injury
      because creatine kinase activity was concurrently increased. Compared with
      baseline values, bile acid concentration and y-glutamyl transferase activity were
      not affected by liver biopsy or crush injury. Plasma sorbitol dehydrogenase
      activity was the most specific indicator of liver injury in both groups.
      Histologic changes correlated poorly with biochemical results, possibly because
      the small area of hepatic parenchyma that was damaged did not affect enzyme
      values substantially.

PMID- 22872979
TI  - Rapid and reliable sedation induced by diazepam and antagonized by flumazenil in
      zebra finches (Taeniopygia guttata).
AB  - Songbirds have emerged as attractive model systems in many areas of biological
      research. Notably, songbirds are used in studies of the neurobiological and
      neuroendocrine mechanisms that shape vocal communication, and zebra finches
      (Taeniopygia guttata) are the most commonly studied species. In these studies,
      some form of chemical restraint is often needed to facilitate procedures and to
      minimize the risk of injury during handling. To determine the minimum dose of the
      benzodiazepine diazepam that is adequate to achieve deep sedation across
      individual birds, a low dose (5 mg/kg) and a high dose (10 mg/kg) was
      administered intramuscularly to 20 zebra finches. Results showed that a 10 mg/kg
      dose of diazepam resulted in deep sedation, defined by dorsal recumbency, which
      was achieved in minutes and lasted for several hours. Sedation was induced
      without complication, because no birds displayed signs of distress during
      sedation or lethargy after recovery, and was adequate to permit minimally
      invasive surgical procedures. In addition, the duration of sedation was dose
      dependent, which provides additional information for researchers who seek to
      match the depth of sedation to their experimental requirements. Finally, complete
      recovery from the deeply sedated state was induced by a 0.3 mg/kg dose of the
      antagonist flumazenil, which enabled birds to more rapidly resume homeostatic
      behaviors to promote well-being and survival. Together, these results indicate
      that diazepam is a safe and reliable sedative for use in zebra finches and
      support specific recommendations to achieve rapid and reliable sedation and
      recovery.

PMID- 22872980
TI  - Surgical removal of a thymoma in a burrowing owl (Athene cunicularia).
AB  - A 12-year-old male burrowing owl (Athene cunicularia) was presented for
      evaluation of a mass in the right cervical region. A thymoma was diagnosed after
      surgical resection and histopathologic evaluation. Extensive adherence of the
      thymoma to the esophagus and suspected invasion into the right jugular vein
      contributed to a poor postsurgical outcome. Diagnosis and treatment of thymomas
      in avian species is similar to that in mammals. Surgical removal of noninvasive
      thymomas is usually curative. Thymomas are rarely reported in avian species and
      this is the first report in a strigiform bird.

PMID- 22872981
TI  - Hypopi of Hypodectes propus (Acari: Hypoderatidae) in two southern crowned
      pigeons (Goura scheepmakeri).
AB  - Necropsy of 2 4-year-old southern crowned pigeons (Goura scheepmakeri) that died
      from a presumed case of botulism revealed hundreds of small, cyst-like structures
      in the pectoral subcutaneous tissues. The structures were identified as
      heteromorphic deutonymphs of Hypodectes propus (Order Astigmata) of the family
      Hypoderatidae. The immobile, immature hypopi were individually encapsulated,
      mostly in adipose tissue, and evoked only a mild inflammatory infiltration of
      predominately macrophages with some heterophilic granulocytes. The infection was
      not considered a serious health problem and was interpreted as an incidental
      finding. To our knowledge, this is a new host record for H. propus.

PMID- 22872982
TI  - Successful treatment of a radioulnar synostosis in a Mississippi kite (Ictinia
      mississippiensis).
AB  - A Mississippi kite (Ictinia mississippiensis) was presented to the Wildlife
      Hospital of Louisiana, School of Veterinary Medicine, Louisiana State University,
      for an inability to fly and was subsequently diagnosed with a minimally
      displaced, closed, simple, short oblique, diaphyseal fracture of the distal third
      of the right ulna. A figure-8 bandage was initially applied to the wing to
      stabilize the fracture. Over a 5-week period, the kite developed progressive
      reduction in wing extension, and serial radiographs revealed a bridging callus at
      the ulnar fracture site, as well as development of a radioulnar synostosis. To
      restore wing function and extension, surgical excision of the bony union between
      the radius and the ulna was performed, after which a polypropylene mesh implant
      was interposed between the 2 bones. Within 2 weeks after the surgical procedure,
      the kite had recovered normal wing extension and was able to fly without
      noticeable impairment. The bird was released 2 weeks after surgery. This case
      illustrates a common complication of external coaptation used as sole means of
      managing fractures of the avian ulna, radius, or both, which results from lack of
      interosseous soft tissue in the antebrachial area. On the basis of the successful
      outcome in this case, surgical excision of the interdiaphyseal callus and
      interposition of a polypropylene mesh could be a viable option for management of
      posttraumatic radioulnar synostosis in birds of prey.

PMID- 22872983
TI  - Malignant lymphoma of T-cell origin in a Humboldt penguin (Spheniscus humboldti)
      and a pink-backed pelican (Pelecanus rufescens).
AB  - Multicentric T-cell lymphomas were diagnosed in two birds from separate
      zoological collections: one in a 27-year-old female Humboldt penguin (Spheniscus
      humboldti) and the second in an adult pink-backed pelican (Pelecanus rufescens).
      The main clinical sign in the penguin was dysphagia caused by lymphoma formation
      in the esophagus. Besides the esophageal lymphoma, neoplastic lymphoid cells were
      observed in the adrenal glands, liver, kidneys, lung, proventriculus, and
      gizzard. The pelican was found dead without a clinical history. Neoplastic
      lymphoid cells were observed in the kidneys, liver, pancreas, spleen,
      ventriculus, and small intestine. Neoplastic cells of the penguin as well as of
      the pelican were immunoreactive to CD3 antigen, suggesting the lymphomas were of
      T-cell origin. In both cases, test results were negative for Marek's disease
      virus, avian leukosis virus, and reticuloendotheliosis virus. In the pelican, a
      skin melanoma was diagnosed on the left throat pouch in addition to the
      multicentric T-cell lymphoma.

PMID- 22872984
TI  - Management of specific and excessive posturing behavior in a hyacinth macaw
      (Anodorhynchus hyacinthinus) by using applied behavior analysis.
AB  - Applied behavior analysis was used in a female hyacinth macaw (Anodorhynchus
      hyacinthinus) to reduce specific, excessive mating-type posturing that had become
      disruptive due to increased frequency, duration, and intensity. A functional
      assessment and intervention design worksheet was used to evaluate behavior
      environment relations and to develop an individualized behavior-change plan. The
      functional assessment indicated that human attention was maintaining the
      behavior. The intervention, differential reinforcement of incompatible behavior,
      was implemented to increase attention for standing upright and to remove
      attention for posturing. Within 1 month, posturing decreased to acceptable levels
      and was replaced with an upright posture. Problem behaviors that appear
      "reproductive" may be responsive to behavior management alone. Applied behavior
      analysis and a functional assessment and intervention design are ideal tools to
      address problem behavior in avian patients.

PMID- 22872985
TI  - You think you want to be a veterinarian: what you wish you had known then that
      you know now.

PMID- 22872986
TI  - Ten years of spatial disorientation in U.S. Army rotary-wing operations.
AB  - INTRODUCTION: Spatial disorientation (SD) has plagued aviation since its
      inception, contributing to numerous lost lives, destroyed or damaged aircraft,
      and a reduction in operational mission effectiveness. Military rotary-wing (RW)
      operations are not immune. The U.S. Army has retired many "legacy aircraft"
      represented in older studies, developed new training regimens for aircrew,
      continued to expand its night vision capabilities, and has prosecuted combat
      operations for some 10 yr utilizing new tactics, techniques, and procedures. For
      these reasons, it is important and relevant to re-engage the subject of SD among
      accidents within the Army's RW community. METHODS: The U.S. Army's Combat
      Readiness/Safety Center database at Fort Rucker, AL, was queried for the previous
      10 yr RW mishaps from fiscal year (FY) 2002 through FY 2011 (FY11 current through
      01 July). Accidents identified as having SD as a contributing factor were
      selected. RESULTS: From FY 2002 to FY 2011, there were 100 Class A through C
      rotary-wing flight mishaps involving SD. This represents 11% of all Class A
      through C rotary-wing flight accidents for this period. Of the 100 SD-related
      accidents, 22% involved fatalities, and 39% involved fatalities and/or injuries.
      The total number of RW SD-related accidents with fatalities represents 31% of the
      total helicopter accidents with fatalities for the 10-yr period. DISCUSSION: This
      review of accident data confirms that SD remains a substantial issue for the Army
      aviation community and reinforces the importance and relevance of SD awareness,
      research, education, and training in RW operations.

PMID- 22872987
TI  - Initial heat stress on subsequent responses to cold water immersion while wearing
      protective clothing.
AB  - INTRODUCTION: In cold water emergency situations, helicopter aircrew will enter
      the water with a raised body temperature due to wearing immersion suits.
      Prewarming has been demonstrated to accelerate core cooling during subsequent
      cold water immersion (CWI) when wearing swimsuits. For this study we hypothesized
      that wearing an immersion suit would slow the rate of cooling in subjects who
      were prewarmed compared to those kept in a normothermic state. METHODS: Two
      different groups of male subjects (age, 24.7 +/- 4.2 yr; height, 183.1 +/- 6.5
      cm; weight, 86.7 +/- 15.0 kg; body fat, 16.8 +/- 3.3%) were used to gather data
      under two conditions: prewarming by exercise (Warm-CWI) and baseline (Base-CWI)
      when wearing a dry immersion suit (2.97 Clo). In Warm-CWI, seven subjects rested
      for 20 min and then cycled on an ergometer cycle for 20 min before immersion in
      water at 5 degrees C for 140 min. In Base-CWI, six subjects were directly
      immersed in 5 degrees C water after resting. RESULTS: Tre and Tsk were
      significantly higher after Warm-CWI at start of CWI, resulting in faster core
      cooling rate, and a drop in Tre and Tsk during the first 10 min. In the long
      term, the overall core cooling did not differ between Warm-CWI (0.34 +/- 0.11
      degrees C x h(-1)) and Base-CWI (0.31 +/- 0.05 degrees C x h(-1)). DISCUSSION:
      Wearing a dry immersion suit eliminates long-term differences in core cooling
      between prewarmed subjects and those kept in a normothermic state. When entering
      cold water with a raised Tre and Tsk, different thermal responses during the
      first 10 min are expected, but this does not alter long-term core cooling.

PMID- 22872988
TI  - Influence of posture on the regulation of cerebral perfusion.
AB  - BACKGROUND: Posture has a major influence on cerebral blood flow (CBF). Unlike
      head-up tilt (HUT), less is known about how CBF is regulated during head-down
      tilt (HDT). We hypothesized that CBF would be elevated during HDT and decreased
      during HUT. METHODS: In 21 healthy young adults, while controlling for end-tidal
      Pco2, we combined concurrent measurements of middle cerebral artery velocity and
      posterior cerebral artery velocity (MCAv and PCAv, respectively), blood pressure
      (BP), and heart rate (HR). Measures were made at rest and, in a randomized order,
      during -90 degrees HDT and +900 HUT. Dynamic cerebral autoregulation was
      quantified using transfer function analysis. In a subgroup, volumetric blood flow
      recordings were obtained in the common carotid artery (CCA; N=11), internal and
      external carotid arteries (ICA; N=8 and ECA; N=6), and vertebral artery (VA;
      N=4). RESULTS: End-tidal Pco2, CCA, ICA, VA, MCAv(mean) and PCAv(mean) remained
      unchanged during -90 degrees HDT and +90 degrees HUT compared to supine. During 
      90 degrees HDT, mean BP (+22 mmHg) and cerebral vascular resistance (CVR) in both
      the MCA and PCA were elevated relative to supine, whereas HR remained unchanged.
      During +900 HUT, when compared to supine, HR increased (+18 bpm), and mean
      arterial pressure (MAP) total power and low frequency (LF) power in the MCA and
      PCA increased. In both the very low frequency (VLF) and LF ranges, coherence
      during +90 degrees HUT increased (P < 0.05 vs. supine) in both the MCA and PCA.
      In contrast, coherence was reduced during -90 degrees HDT. DISCUSSION: Despite
      marked changes in perfusion pressure with HUT or HDT, our findings indicate that
      cerebral perfusion is well maintained during acute severe changes in posture.

PMID- 22872989
TI  - Physiological responses of astronaut candidates to simulated +Gx orbital
      emergency re-entry.
AB  - INTRODUCTION: We investigated astronaut candidates' physiological and
      pathological responses to +Gx exposure during simulated emergency return from a
      running orbit to advance astronaut +Gx tolerance training and medical support in
      manned spaceflight. METHODS: There were 13 male astronaut candidates who were
      exposed to a simulated high +Gx acceleration profile in a spacecraft during an
      emergency return lasting for 230 s. The peak value was 8.5 G. Subjective feelings
      and symptoms, cardiovascular and respiratory responses, and changes in urine
      component before, during, and after +Gx exposure were investigated. RESULTS:
      Under high +Gx exposure, 15.4% of subjects exhibited arrhythmia. Heart rate (HR)
      increased significantly and four different types of HR response curves were
      distinguished. The ratio of QT to RR interval on the electrocardiograms was
      significantly increased. Arterial oxygen saturation (SaO2) declined with
      increasing G value and then returned gradually. SaO2 reached a minimum (87.7%) at
      3 G during the decline phase of the +Gx curve. Respiratory rate increased
      significantly with increasing G value, while the amplitude and area of the
      respiratory waves were significantly reduced. The overshoot appeared immediately
      after +Gx exposure. A few subjects suffered from slight injuries, including
      positive urine protein (1/13), positive urinary occult blood (1/13), and a large
      area of petechiae on the back (1/13). CONCLUSIONS: Astronaut candidates have
      relatively good tolerance to the +Gx profile during a simulation of spacecraft
      emergent ballistic re-entry. However, a few subjects exhibited adverse
      physiological responses and slight reversible pathological injuries.

PMID- 22872990
TI  - Drugs and alcohol found in civil aviation accident pilot fatalities from 2004
      2008.
AB  - INTRODUCTION: The Federal Aviation Administration (FAA) Office of Aerospace
      Medicine sets medical standards needed to protect the public and pilots from
      death or injury due to incapacitation of the pilot. As a part of this process,
      toxicology testing is performed by the FAA on almost every pilot who is fatally
      injured in an aviation accident to determine the medical condition of the pilot,
      medications used by the pilot at the time of the accident, and the extent of
      impairment, if any. METHOD: The data were extracted from the FAA toxicology
      database for all pilots who died from 2004 to 2008 in aviation accidents.
      RESULTS: The laboratory received and tested specimens from 1353 pilots who died
      in aviation accidents between 2004 and 2008; 507 of these pilots were found to be
      taking drugs and 92 had ethanol in excess of 0.04 g x dl(-1). DISCUSSION: This
      study was conducted to determine the extent of drug use in pilots who have died
      in aviation accidents from 2004 to 2008 and to determine the types of drugs most
      commonly found. A comparison of previously published reports with this study's
      report was made to determine trends in drug use by pilots who have died in
      aviation accidents over the past 20 yr. Factors were discussed that could
      influence drug trends. Diphenhydramine, an H1 antihistamine with impairing
      properties, is the most commonly found drug in pilots who died in an aviation
      accident.

PMID- 22872991
TI  - Reliability of plasma D-dimers for predicting severe neurological decompression
      sickness in scuba divers.
AB  - BACKGROUND: A low-grade process of coagulation activation in association with
      severe neurological decompression sickness (DCS) in divers has been anecdotally
      observed. We aimed to investigate whether measurement of plasma D-dimers and
      other hemostatic parameters in injured scuba divers were effective as prognostic
      biomarkers of neurological DCS, and we compared the diagnostic accuracy of a
      combination of D-dimers test and initial clinical assessment with either one
      alone. METHODS: Eligible for the study were 84 recreational divers (69 men, 46 +/
      10 yr; 15 women, 44 +/- 8 yr) referred for neurological DCS in 2007-2011 and
      treated with hyperbaric oxygen. Blood tests were collected for D-dimers,
      fibrinogen, and platelet count with a time interval less than 8 h upon admission.
      Presentation severity was rated numerically for the acute event with a validated
      scoring system and clinical outcome was assessed by a follow-up examination at 3
      mo. Indices of accuracy for D-dimers test, initial clinical score, and
      combination were estimated. RESULTS: Incomplete recovery was reported in 26% of
      patients with a definite relationship between elevated D-dimers and presence of
      sequelae after multivariate analysis. We did not find differences for other blood
      coagulation variables between outcome groups. Combination of positive D-dimers
      (cut-off value of 0.40 microg x ml(-1)) with severe initial presentation attained
      a higher diagnostic accuracy than either method alone (post-test probabilities =
      100%, 86%, and 57%, respectively). CONCLUSION: This study suggests that
      determination of plasma D-dimers, a marker of activation coagulation, improve the
      prognostication of neurological DCS affecting scuba divers when combined with
      presenting severity score.

PMID- 22872992
TI  - Flight hours and flight crew performance in commercial aviation.
AB  - OBJECTIVE: To examine the relationship between a pilot's flight hours and their
      performance. BACKGROUND: There is current debate in the aviation industry on the
      minimum hours required for first officers to gain before they can fly for an
      airline. Despite years of pilot training and licensing, there are very little
      data available to determine whether or not pilot performance varies as a function
      of total hours within an airline environment. METHOD: Flight crew performance was
      measured during 287 sectors of normal operations against a set of technical and
      nontechnical measurements. Flightcrew were grouped into a categorical variable
      which defined low and high experience groups according to industry accepted
      thresholds. RESULTS: There were no statistically significant differences between
      experience groups for First Officers or Captains against the set of technical
      measures; however, there were minor differences with regard to nontechnical
      measures as a function of crew composition. There was also a difference in
      automation use, with First Officers with less than 1500 h keeping the autopilot
      engaged until a significantly lower altitude. DISCUSSION: Despite on-going debate
      that low-hour First Officers are not as capable as their more experienced
      colleagues, we found no evidence of this in our study.

PMID- 22872993
TI  - An exercise protocol designed to control energy expenditure for long-term space
      missions.
AB  - INTRODUCTION: Astronauts experience weight loss during spaceflight. Future space
      missions require a more efficient exercise program not only to maintain work
      efficiency, but also to control increased energy expenditure (EE). When
      discussing issues concerning EE incurred through exercise, excess post-exercise
      energy expenditure (EPEE) must also be considered. The aim of this study was to
      compare the total EE, including EPEE, induced by two types of interval cycling
      protocols with the total EE of a traditional, continuous cycling protocol.
      METHODS: There were 10 healthy men, ages 20 to 31 yr, who completed 3 exercise
      sessions: sprint interval training (SIT) consisting of 7 sets of 30-s cycling at
      120% VO2max with a 15-s rest between each bout; high-intensity interval aerobic
      training (HIAT) consisting of 3 sets of 3-min cycling at 80-90% VO2max with a 2
      min active rest at 50% VO2max; and continuous aerobic training (CAT) consisting
      of 40 min of cycling at 60-65% VO2max. During each session, resting metabolic
      rate, exercise EE, and a 180-min post-exercise EE were measured. RESULTS: The
      EPEEs during the SIT, HIAT, and CAT averaged 32 +/- 19, 21 +/- 16, and 13 +/- 13
      kcal, and the total EE for an entire exercise/ rest session averaged 109 +/- 20,
      182 +/- 17, and 363 +/- 45 kcal, respectively. While the EPEE after the CAT was
      significantly less than after the SIT, the total EE with the CAT was the greatest
      of the three. DISCUSSION: The SIT and HIAT would be potential protocols to
      control energy expenditure for long space missions.

PMID- 22872994
TI  - Cerebral near-infrared spectroscopy to evaluate anti-G straining maneuvers in
      centrifuge training.
AB  - INTRODUCTION: Over the past decade, near-infrared spectroscopy (NIRS) has emerged
      as an easily manageable noninvasive method for the continuous monitoring of
      cerebral cortical oxygenation during +Gz exposure. NIRS is also used to evaluate
      pilot trainees' ability to adequately perform anti-G straining maneuvers in the
      course of centrifuge training. This study aimed to determine the general patterns
      and individual differences in NIRS recordings during +Gz exposure. METHODS: There
      were 22 healthy male cadets who participated in the study. The centrifuge
      training profiles included a gradual onset run (GOR, onset rate of 0.1 Gz x s(
      1)) and short-term repeated exposures, with Gz levels from 4 to 7 Gz at an onset
      rate of 1.0 Gz x s(-1) (rapid onset run, ROR). Cortical tissue hemoglobin
      saturation (tissue oxygenation index, TOI) and changes in the concentration of
      oxygenated hemoglobin (O2Hb) were recorded from the right forehead during the
      period of Gz exposure. RESULTS: Most of the subjects successfully performed an
      anti-G straining maneuver and maintained or increased the cerebral oxygenation
      level during Gz exposure. In four subjects, however, oxygenation decline was
      observed at levels over 4 Gz, even though their anti-G systems were functioning.
      In contrast to the O2Hb response, TOI, which reflects intracranial oxygenation
      changes, was decreased during the anti-G straining maneuver at Gz onset or during
      the countdown to a ROR exposure. CONCLUSION: Although NIRS is an effective tool
      for monitoring anti-G straining maneuver performance, it should be carefully
      evaluated in terms of intracranial oxygenation results.

PMID- 22872995
TI  - Prediction of crew health effects from air samples taken aboard the International
      Space Station.
AB  - INTRODUCTION: Spaceflight aboard the International Space Station (ISS) involves
      stays of individual crewmembers for up to 6 mo during which they are exposed to a
      complex mixture of airborne pollutants. Methods to predict specific health
      effects from exposure to a mixture of air pollutants are not well developed.
      Herein, air monitoring data from the ISS are used to demonstrate a new method to
      estimate a threshold for possible health effects from exposure to mixtures.
      METHODS: An empirical, additive approach was developed to transform monthly air
      pollutant data, which had been obtained primarily by gas chromatography-mass
      spectrometry from samples of ISS air, to threshold (T) values for 16 adverse
      health effect groups. Spacecraft maximum allowable concentrations (SMACs),
      available for most spacecraft air pollutants, were used to form target
      organ/effect groups, from which group T values were estimated. If T >1 for a
      group, then there is an unacceptable risk of the toxic effect. RESULTS: Samples
      of air taken from the ISS in 2010 revealed that all 16 toxicological groups were
      within safe limits. Highest T values were as follows: mucosal irritants (0.53 +/-
      0.44), headache (0.52 +/- 0.06), central nervous system depression (0.25 +/-
      0.06), and cardiac sensitization (0.13 +/- 0.04). DISCUSSION: The additive model
      is supported by limited inhalation data on rats in the literature. Our
      predictions of no adverse effect on crew health are useful as part of NASA's
      Lifetime Surveillance of Astronaut Health (LSAH). If one of the 16 levels had
      exceeded T=1, then standard surveillance could be supplemented to address this
      potential health risk.

PMID- 22872996
TI  - Fatigue reporting among aircrew: incidence rate and primary causes.
AB  - INTRODUCTION: In this study we describe our experience of voluntary fatigue
      reporting among pilots and cabin crew. METHOD: This was a prospective study to
      determine the crude incidence rate and primary cause of fatigue report form
      submission among cabin crew and pilots within one airline. All crew duties had
      already undergone scrutiny at the 'roster build' stage to ensure compliance with
      fatigue control measures. Reports were investigated by the airline's medical
      officer to determine the primary cause of fatigue and then allocated to one of
      five categories. The frequency and proportion of reports within each category was
      determined. RESULTS: The crude incidence rate of fatigue report submission was
      103 and 68 cases per 1000 persons per year for pilots and cabin crew,
      respectively. The primary cause for 27% of reports was attributed to the rostered
      duty pattern. Of the reports, 24% were primarily caused by roster disruption, 17%
      by problems with layover accommodation or transport, 23% by a domestic issue, and
      9% had no obvious cause or were deemed invalid. A subanalysis of the 'domestic'
      category revealed that half had a primary cause attributable to commuting to or
      from the workplace. CONCLUSION: The number and trend of reports received per
      month can be used to detect otherwise unknown fatigue hazards and identify where
      improvements can be made. Fatigue reports allow individual crewmembers to give
      vital feedback on 'whole-of-life' fatigue risks, both inside and outside the
      workplace.

PMID- 22872997
TI  - Peripheral neuropathy of the extremity after hyperbaric exposure.
AB  - BACKGROUND: Neurological deficits occurring after diving or hyperbaric exposure
      are typically due to central nervous system decompression illness (DCI). However,
      consideration of alternate diagnoses is sometimes warranted. CASE REPORT: A 47-yr
      old female hyperbaric technician developed foot drop 2 d following her last
      hyperbaric exposure. She had worked in chamber once daily at 45 fsw for 90 min.
      The breathing gas was air until the last 15 min, during which she breathed
      oxygen. Her history was complicated by a gastric bypass and weight loss totaling
      160 pounds within the preceding 9 mo. She was treated for presumed neurological
      DCI without improvement. The adherence to safe hyperbaric protocols, delayed
      presentation, ongoing medical issues, and lack of response to therapy brought the
      diagnosis into question. Extensive neurological evaluation, including nerve
      conduction studies, revealed a common peroneal mononeuropathy. We concluded that
      her neuropathy was more likely due to extreme weight loss and malnutrition than
      peripheral nervous system DCI. DISCUSSION: There are rare reports of DCI
      affecting the peripheral nerves of the extremities. A literature search revealed
      only three such cases. Two further reports describe peripheral neuropathy in the
      extremities of divers that were attributed to other causes: compression by a
      weight belt and vasculitis. However, peroneal neuropathy is one of the most
      common focal mononeuropathies of the lower extremity and has been reported in
      association with extreme weight loss and malnutrition. We attributed our diver's
      neuropathy to extreme weight loss and malnutrition rather than DCI.

PMID- 22872998
TI  - Commercial air travel after intraocular gas injection.
AB  - Passengers with intraocular gas are at risk of profound visual loss when exposed
      to reduced absolute pressure within the cabin of a typical commercial airliner.
      Information provided on the websites of the world's 10 largest airlines offer a
      considerable range of opinion as to when it might be safe to fly after gas
      injection. Physicians responsible for clearing pseassengers as 'fit to fly'
      should be aware modern retinal surgical techniques increasingly employ long
      acting gases as vitreous substitutes. The kinetics of long-acting intraocular
      gases must be considered when deciding how long after surgery it is safe to
      travel. It is standard practice to advise passengers not to fly in aircraft until
      the gas is fully resorbed. To achieve this, it may be necessary to delay travel
      for approximately 2 wk after intraocular injection of sulfur hexafluoride (SF6)
      and for 6 wk after injection of perfluoropropane (C3F8).

PMID- 22872999
TI  - You're the flight surgeon: cholera.

PMID- 22873000
TI  - You're the flight surgeon: autoimmune polyglandular syndrome type 2.

PMID- 22873001
TI  - This month in aerospace medicine history.

PMID- 22873002
TI  - Terrorism, conflict and the after effects of war.

PMID- 22873003
TI  - The Holdstock-Piachaud Prize 2011.

PMID- 22873004
TI  - Holdstock-Piachaud Prize essay. The dilemma of neutrality: to what extent can
      humanitarian assistance be combined with efforts to promote development?

PMID- 22873005
TI  - Holdstock-Piachaud Prize essay. War and the systematic devastation of women: the
      call for increased attention to traumatic gynaecological fistulae.

PMID- 22873006
TI  - Holdstock-Piachaud Prize essay. Sustainable health care, Afghan style.

PMID- 22873007
TI  - Listening to those called terrorists; the case for a public forum within the
      United Nations.

PMID- 22873008
TI  - Peace-building through health: challenges and opportunities for an American NGO
      working with Israelis and Palestinians.

PMID- 22873009
TI  - Trauma spectrum disorders: emerging research on polytrauma, recovery and
      reintegration of service members, veterans and their families.

PMID- 22873010
TI  - Mental health survey among landmine survivors in Siem Reap province, Cambodia.
AB  - Many survivors of the Khmer Rouge period in Cambodia and the subsequent war with
      Vietnam have now returned to Cambodia. In this two-stage household cluster survey
      in Siem Reap Province in Cambodia, we explored the mental health consequences on
      166 landmine injury survivors selected from 1000 household in 50 clusters and an
      oversample of all landmine survivors. We found a prevalence of anxiety of 62% for
      all respondents, 74% for depression, and 34% for post-traumatic stress disorder
      (PTSD). These prevalences were statistically significantly higher than among the
      adult population who had not been injured by landmines. These data underscore the
      importance of providing mental health care services for the people in Siem Reap
      Province in Cambodia who have been injured by landmines.

PMID- 22873011
TI  - Marijuana: modern medical chimaera.
AB  - Marijuana has been used medically since antiquity. In recent years there has been
      a resurgence of interest in medical applications of various cannabis
      preparations. These drugs have been cited in the medical literature as potential
      secondary treatment agents for severe pain, muscle spasticity, anorexia, nausea,
      sleep disturbances, and numerous other uses. This article reviews the research
      literature related to medical applications of various forms of cannabis. Benefits
      related to medical use of cannabinoids are examined and a number of potential
      risks associated with cannabis use, both medical and recreational, are
      considered. There is a clearly identified need for further research to isolate
      significant benefits from the medical application of cannabinoids and to
      establish dosage levels, appropriate delivery mechanisms and formulations, and to
      determine what role, if any, cannabinoids might play in legitimate medical
      applications. It is also imperative to determine if reported dangers pose a
      significant health risks to users.

PMID- 22873012
TI  - Differences in drinking expectancies and motives for regular education and
      special education high school students with emotional/behavioral disorders.
AB  - Alcohol expectancies and drinking motives were compared for regular education
      students (n=159) and students with emotional/behavioral disorders (EBD) receiving
      special education services (n=51). Differences existed between groups with
      respect to expected negative social consequences and emotional and physical
      outcomes associated with drinking. Across groups, drinkers reported more positive
      alcohol expectancies than non-drinkers, while non-drinkers reported more negative
      alcohol expectancies than drinkers. Differences also existed between the regular
      education and EBD students who drank with respect to coping, conformity, and
      social motives. Accounting for sample sizes differences, the relationship between
      alcohol use and negative physical effect was stronger for regular education
      students, while the relationship between alcohol use and conformity motives was
      stronger for the EBD group.

PMID- 22873013
TI  - An evaluation of immediate outcomes and fidelity of a drug abuse prevention
      program in continuation high schools: project towards no drug abuse (TND).
AB  - The present study provides an implementation fidelity, process, and immediate
      outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention
      program targeting continuation high school youth (n=1426) at risk for drug abuse.
      A total of 24 schools participated in three randomized conditions: TND Only, TND
      and motivational interviewing follow-up, and no treatment control. Fidelity was
      high: across program schools the curriculum was implemented as intended and was
      received favorably by students. Relative to controls, intervention conditions
      produced effects on hypothesized mediators, including greater gains in program
      related knowledge, greater reductions in drug use intentions, and positive
      changes in motivation. However, few generalizations to attitudes and intentions
      regarding risky sexual behavior were found. The pattern of results suggests that
      the experimental manipulations worked as intended.

PMID- 22873014
TI  - What if you caught them using? Prospective teachers' beliefs about responding to
      student substance use.
AB  - This survey research examined how prospective teachers' (N=384) beliefs about the
      nature of adolescence, their substance use, and their preparedness for dealing
      with substance use situations are linked to perceptions of how they would respond
      to students' possession or use of cigarettes, alcohol, and marijuana at school.
      Results suggested that prospective teachers are not prepared for these
      situations. Feeling prepared, perceiving that few adolescents engage in problem
      behavior, and low personal substance use were associated with more responses to
      substance use situations. Women were more likely than men to think they would
      respond to adolescent substance use yet they felt less prepared. Males who used
      alcohol, cigarettes, or marijuana recently were the least likely to perceive that
      they would respond to adolescents using substances at school.

PMID- 22873015
TI  - Starting to drink: the experiences of Australian lower secondary students with
      alcohol.
AB  - This study describes Australian year eight students' (13-14 years old)
      experiences with alcohol in terms of communication with parents, initiation into
      drinking, patterns of consumption, context of use, and harms experienced. The
      sample comprised 521 year eight students from four state government secondary
      schools in the state of Victoria. Three of the schools are in Melbourne, the
      capital of Victoria; the fourth is in a rural center. Female and rural students
      were more likely to talk to parents about alcohol, but this was not associated
      with safer drinking. Initiation into drinking was higher among rural students.
      Rural students also drank more, were more likely to drink without adult
      supervision, to drink to get drunk, and drink more than planned. Student drinkers
      experienced just over four alcohol-related harms on average in 12 months, with
      some indication of greater harm among rural students. Higher levels of drinking
      by rural students, accompanied by more risky patterns of consumption and the
      possibility of greater harm, supports prioritizing interventions in rural
      schools.

PMID- 22873016
TI  - A review of social host policies focused on underage drinking parties:
      suggestions for future research.
AB  - Underage drinking continues to be a public health concern, partially due to the
      ease in which adolescents obtain alcohol and consume it in private locations.
      States and municipalities have implemented strategies to counteract this,
      including adopting public policies called social host policies, despite limited
      evidence of effectiveness. Traditionally, these laws have held adults accountable
      for furnishing alcohol to underage drinkers. However, states and communities are
      using another policy, also called social host, to deter underage drinking parties
      where easy access to alcohol and high-risk use occurs. These innovative laws hold
      individuals who control the property accountable for underage drinking that
      occurs there, regardless of alcohol source. We conducted a critical analysis of
      social host policies focused on hosting underage drinking parties and constructed
      a conceptual model to understand their targeted factors. Future research
      recommendations are discussed.

PMID- 22873017
TI  - Order and again order.

PMID- 22873018
TI  - Anterior open bite correction using bite block: a case report.
AB  - Several etiological factors that result in dental and/or skeletal alterations
      make the open bite a type of malocclusion with several treatment alternatives.
      Corrective fixed orthodontics in conjunction with mechanical or functional
      orthopedics is a routine approach in correcting this problem. However,
      orthosurgical treatment must never be discarded for cases with skeletal
      involvement. This article describes a clinical case which, despite involving
      skeletal aspects, was treated satisfactorily using a passive bite-block appliance
      in conjunction with corrective fixed orthodontics.

PMID- 22873019
TI  - Cone beam computed tomography: third eye in diagnosis and treatment planning.
AB  - Orthodontic treatment of adult patients with complex dental problems is done in
      interdisciplinary teams where different specialists of dental medicine have to
      manage a vast quantity of data. In such complicated cases good diagnostic tools
      and easy communication are essential Computer science has an increasing impact in
      almost every aspect of the orthodontic practice, research and education. Within
      the past decade, technology termed "cone beam computed tomography" (CBCT) has
      evolved that allows 3-D visualization of the oral and maxillofacial complex from
      any plane. With the development of Cone Beam Computed Tomography, there has been
      a drastic reduction in radiation exposure to the patient, which allows its use
      for safely obtaining three dimensional images of the craniofacial structures.
      This should allow the clinician to visualize the hard and soft tissues of the
      craniofacial region from multiple perspectives, which could have far-reaching
      implications for treatment planning in orthodontics and orthognathic surgery.
      This paper shall discuss in detail the principles of the cone beam computed
      tomography and its applications in the field of orthodontics.

PMID- 22873020
TI  - A novel approach for treatment of mandibular deficiency with vertical growth
      pattern.
AB  - This case illustrates the treatment of a 10.5-year-old girl with Class II
      Division I malocclusion and mandibular deficiency combined with vertical growth
      pattern. The patient was treated by a modified R-Appliance and extraction of
      upper and lower first bicuspids. Modified R-Appliance was used for 18 months
      followed by 17 months of Posterior bite plate, after which favorable correction
      of the malocclusion was observed. The SNB angle increased by 5 degrees and the
      IMPA decreased by 11 degrees. This case demonstrates that modified R-Appliance
      can be a suitable method for treatment of mandibular deficient cases with
      verticalgrowth pattern.

PMID- 22873021
TI  - Masseter muscle bite force in first bicuspid and collapsed occlusion cases.
AB  - The masseter muscle is the primary bite force generator for chewing and
      swallowing. Masseter muscle strength was recorded on 89 subjects using
      electromyography. Subject groups were separated into 4-bicuspid extraction cases,
      collapsed occlusions, and controls. Data was averaged and analyzed. The control
      group displayed the greatest strength.

PMID- 22873022
TI  - The importance of the diagnostic setup in the orthodontic treatment plan.
AB  - The aim of this study was to address the importance of the diagnostic setup by
      examining two cases where diagnostic setups were made in order to determine the
      treatment plan. The diagnostic setup is a fundamental aid and should be used when
      there are doubts in the orthodontic planning.

PMID- 22873023
TI  - Nasolabial angle: a perception of treatment needs.
AB  - The nasolabial angle holds a very important position in the treatment planning
      process for an orthodontic case, especially in today's soft tissue paradigm. This
      study was therefore conducted to compare the mean preference scores for
      orthodontic treatment need considering the nasolabial angle among orthodontists,
      orthodontic patients and their parents.

PMID- 22873024
TI  - Root resorption after orthodontic treatment: a review.
AB  - Root resorption that occurs in permanent teeth is an unwanted process and is
      considered pathologic. Although apical root resorption occurs in individuals who
      have never experienced orthodontic tooth movement, the incidence among treated
      individuals is seen to be significantly higher. Some resorption occurs in most
      orthodontic patients, but because of repair the changes are difficult to detect
      with radiographic examination and therefore are clinically insignificant. This
      article gives a review of the various types of root resorption, the etiological
      factors, the biology and the identification of root resorption.

PMID- 22873025
TI  - Treatment of developing Class II Division 1 malocclusion with Jumper Twin Block.
AB  - The objective of this study was to determine dental and skeletal effects of the
      jumper twin block appliance in the treatment of developing Class II, Division I
      malocclusion. METHODS: 15 girls aged 9 to 11 years old with class II division 1
      and samephysical maturation status were included in the study over one year.
      Cephalometric data and study models were analyzed statistically with Paired t
      test. RESULTS: The jumper twin block had skeletal and dental effects. Stimulation
      of forward mandibular growth, backward displacement of the maxilla, significant
      increase in the anterior and posterior facial height, retroclination of the upper
      incisors, proclination of the lower incisors and significant improvement of the
      overjet and overbite had been found. CONCLUSIONS: The jumper twin block appliance
      with gradual bite advancement was effective in treatment of developing Class II
      division 1 malocclusion.

PMID- 22873026
TI  - Surgical-orthodontic treatment of Class I malocclusion with maxillary vertical
      excess--a case report.
AB  - This article describes the treatment of an adult male with vertical maxillary
      excess, excessive gingival display on smiling, a convex profile, proclined upper
      and lower incisors, and crowded lower anteriors with severe lip incompetence. The
      therapy included stages: (1) Pre surgical orthodontics- leveling and aligning of
      the maxillary and mandibular arch with closure of all extraction spaces. (2)
      Surgical phase-Lefort I osteotomy for superior maxillary impaction, 5 mm of
      anterior and 3 mm of posterior impaction ofmaxilla was done. (3) Post surgical
      orthodontics for finishing and detailing. The treatment lasted 16 months;
      improved facial esthetics significantly; and resulted in a normal occlusion,
      overjet, and overbite.

PMID- 22873027
TI  - The Carriere Distalizer: simple and efficient.

PMID- 22873028
TI  - Give and be rich.

PMID- 22873029
TI  - Who should have or not have an axillary node dissection with breast cancer?
AB  - There have been dramatic changes in the approach to the axilla in women with
      breast cancer over the last 100 years, reflecting the evolution in our
      understanding of the underlying tumor biology, reduced disease burden because of
      early detection, and advances in all breast cancer treatment modalities. The
      approach to the axilla needs to be individualized, much like the extent of
      surgery for the primary tumor. Axillary dissection remains an important
      intervention for patients with more locally advanced disease. However, in
      patients with early-stage breast cancer, in whom regional recurrence is extremely
      low, the added benefit of an ALND has yet to be confirmed.

PMID- 22873030
TI  - Intestinal stomas: indications, management, and complications.
AB  - The ability to appropriately construct and care for an ostomy is crucial to good
      colorectal surgical practice. Enterostomal therapy is critical to the successful
      management of ostomies and their complications. Although associated with
      morbidity, a well-constructed ostomy can provide our patients with a good,
      durable QoL.

PMID- 22873031
TI  - Zero surgical site infections: is it possible?

PMID- 22873032
TI  - Does simulation training improve outcomes in laparoscopic procedures?

PMID- 22873033
TI  - Hypertonic resuscitation after severe injury: is it of benefit?
AB  - There is a wealth of preclinical data suggesting potential benefit from the
      administration of hypertonic solutions after severe injury with hypovolemic
      shock, including improved tissue perfusion, improved flow through the
      microcirculation, and modulation of the inflammatory response, which may mitigate
      subsequent organ failure. However, despite these potential advantages, clinical
      trials of hypertonic resuscitation early after injury have failed to demonstrate
      significant benefit for resuscitation of hemorrhagic shock, and although there is
      no difference in overall mortality, there appears to be a trend toward earlier
      mortality among those receiving hypertonic fluids. Likewise, for TBI there are
      data suggesting that hypertonic fluids should support cerebral perfusion and
      mitigate intracranial hypertension, yet the clinical trials of early
      administration to these patients have also failed to show benefit. Further study
      is warranted in this patient population, as a longer period of hypertonicity may
      be required to show a clinical effect. Assessment of long-term neurologic outcome
      in this patient population remains the gold standard in determining benefit.

PMID- 22873034
TI  - What is the prognosis after retransplantation of the liver?
AB  - In patients with failing liver grafts, hepatic retransplantation cannot be
      abandoned for the ethical and practical reasons that have been detailed
      previously. The current recommendations involve a strategy for risk
      stratification of retransplant candidates. The long-term patient and graft
      survival outcomes after ReLT are excellent and acceptable for the low and
      intermediate groups, respectively. However, pursuing ReLT in transplant
      candidates in the high-risk category cannot be recommended. Furthermore, ReLT
      should be reserved for centers equipped to manage the difficulties of the
      endeavor because it is a technically demanding operation that requires surgical
      expertise and excellent anesthesiology and critical care support both before and
      after transplantation.

PMID- 22873035
TI  - Screening for abdominal aortic aneurysms.
AB  - Ruptured AAA ranks as the 15th leading cause of death overall in the United
      States, and the 10th leading cause of death in men older than 55 years. Early
      identification of AAA can save livesand diminish cost. Screening programs
      havebeen implemented and studied in other countries and have shown a measurable
      and significant reduction in overall rate of aneurysm-related death. Currently,
      one-time screening of a small number of ever-smoking men when they turn 65
      screening is not widely used in the United States and Medicare, at best, provides
      one-time screening of a small number of ever-smoking men when they turn 65 years
      old. Because more than 30,000 individuals in the United States die each year of
      ruptured AAA, a great deal of progress must be made to eradicate rupture from
      aneurysmal disease. A more comprehensive system of screening is required and this
      should be uniformly applied to the U.S. population. It is hoped that scoring
      systems such as the one outlined in this article, if widely adopted, can greatly
      enhance screening for aneurysmal disease and prevent the high mortality that
      stems from this serious vascular disease.

PMID- 22873036
TI  - Novel management strategies in the treatment of severe Clostridium difficile
      infection.
AB  - CDI is increasing in incidence and severity. Clinicians must have a low threshold
      to consider the diagnosis and to treat patients with the clinical syndrome and
      risk factors before laboratory confirmation of the diagnosis. In patients who
      have signs of advanced disease, escalation of care with antimicrobial strategies
      and multidisciplinary care including surgical consultation is necessary.
      Furthermore, lowering the threshold for surgery compared with traditional
      approaches likely results in improved survival. Novel surgical approaches may
      obviate total abdominal colectomy and the associated immediate and long-term
      morbidity in this often fragile patient population, thus allowing clinicians to
      embrace surgical therapy earlier in the course of severe, complicated disease.

PMID- 22873037
TI  - The genetic counselor: an important surgical ally in the optimal care of the
      cancer patient.
AB  - Genetic counselors and surgeons both have important roles in the care of patients
      with hereditary cancer predisposition syndromes. Surgeons have the initial
      responsibility to identify and refer high-risk patients. Genetic counselors'
      specialized skill sets are then used in the risk assessment and genetic
      evaluation of such patients and their at-risk family members, and this may be
      performed in multiple settings. As discussed in this article, these roles and the
      processes of genetic counseling and genetic testing may be enhanced through
      multiple surgeon and genetic counselor collaborations. Continued medical
      management of patients and families with hereditary cancer predisposition
      syndromes becomes the responsibility of patients and their multiple health care
      providers. Box 7 provides a list of resources to assist in finding a local
      genetic counselor. Because there are various opportunities for surgeons and
      genetic counselors to collaborate, the authors urge surgeons to recognize the
      importance of, identify, and work in partnership with a local genetic counselor
      because that relationship sets the stage for optimal care of the cancer patient.

PMID- 22873038
TI  - Readmission rates after abdominal surgery: can they be decreased to a minimum?

PMID- 22873039
TI  - Superiority of minimally invasive parathyroidectomy.
AB  - Because greater than 80% of spontaneous cases of primary hyperparathyroidism are
      caused by a single adenoma, BCE of the neck, which has long been the approach of
      choice, is being replaced. Focused parathyroidectomy has been made possible by
      advances in preoperative parathyroid localization and IOPTH monitoring, which
      allows confirmation of cure and confirmation of the absence of MGD without
      visualizing all 4 parathyroids. Several techniques for focused parathyroidectomy
      exist, but open MIP through an incision of 2 to 3 cm with surgeon-administered
      locoregional anesthesia seems to improve on the already high success rate and low
      morbidity associated withimproe on bilateral exploration. In addition, MIP is
      associated with numerous secondary benefits such as decreased hospital cost,
      improved patient satisfaction, decreased operative time, and same-day discharge.
      Bilateral exploration will remain the standard of care for most patients with
      multigland or syndromic disease. Most patients with sporadic PHPT are candidates
      for MIP.

PMID- 22873040
TI  - Current treatment of papillary thyroid microcarcinoma.
AB  - PTMC is being diagnosed with increasing frequency and generally has an excellent
      prognosis with less than 0.5% disease-specific mortality. Better prognostic
      stratification, especially for high-risk patients, helps to optimize surgical
      care. Older age, extrathyroidal invasion, lymph node involvement, and distant
      metastases are usually regarded as the most potent risk factors for patients with
      PTMC. Total or near-total thyroidectomy is advocated as the initial therapy for
      most primary PTMCs, whereas neck dissection is only recommended with the presence
      of cervical lymphadenopathy or T4 tumors. ATA suggests that postoperative RAI
      ablations be administrated to patients with gross extrathyroidal invasion or
      distant metastases. RAI ablation may also facilitate the use of serum Tg
      concentrations for postoperative risk assessment.

PMID- 22873041
TI  - Use of computed tomography in the emergency room to evaluate blunt
      cerebrovascular injury.
AB  - BCVI remains a potentially devastating consequence of blunt-force trauma.
      However, over the past decades significant advances have been made in
      understanding the pathophysiology, risk factors, and natural history of BCVI.
      Given the initial asymptomatic period, there is time to diagnose and treat these
      lesions before the onset of neurologic insult. This early recognition and
      intervention greatly improves morbidity and mortality directly associated with
      BCVI. Screening criteria have been identified and reviewed. All patients at risk
      of BCVI, based on mechanism of injury and risk factors, should be rapidly
      evaluated for possible injury. It is the authors' current belief that even the
      newest generation of CT scanners has not been proved to reliably diagnose BCVI.
      Until further work is done to advance the technology of CTA and prove its
      equivalence to DSA, there exists too much potential neurologic morbidity and
      mortality for one to rely on CTA alone (Table 2). Given the variable, and often
      low, reported sensitivities of CTA, the cost analysis done by Kaye and colleagues
      [23] would also recommend initial DSA as being cost-effective in avoiding the
      long-term devastating sequelae of stroke. At the time of writing the authors
      recommend that CTA be included in an algorithm to evaluate BCVI, but the current
      data are too disparate with widely variable reported sensitivities, and the risk
      of missed injury and stroke too severe, to rely on CTA as the definitive
      diagnostic or screening test for BCVI. Rather, abnormal CTA findings should be
      added to the traditional screening criteria to identify patients at risk of BCVI;
      these patients should be evaluated with DSA for definitive screening. Adding
      abnormal CTA findings to the traditionally described BCVI screening criteria
      widens the criteria substantially, allowing identification of almost all of the
      elusive 20% of patients traditionally not identified with basic screening
      criteria. In addition, given the high specificity of CTA and the decreased
      morbidity of BCVI with rapid institution of treatment, the authors recommend
      beginning a low-dose heparin drip (if there are no contraindications to
      anticoagulation) based on CTA findings while awaiting the confirmatory DSA.
      Despite advances in CTA technology in recent years, DSA currently remains the
      gold standard for the diagnosis of BCVI. All patients with standard risk factors
      for BCVI, or abnormal findings on CTA, should undergo DSA as the screening test
      of choice for BCVI.

PMID- 22873042
TI  - How important is glycemic control during coronary artery bypass?
AB  - In summary, poor perioperative glycemic control in patients undergoing CABG is
      associated with increased morbidity and mortality. Maintaining serum glucose less
      than or equal to 180 mg/dL in patients with diabetes during CABG reduces
      morbidity and mortality, lowers the incidence of wound infections, reduces
      hospital length of stay, and enhances long-term survival. In nondiabetic patients
      undergoing CABG surgery, maintaining serum glucose less than 180 mg/dL has also
      resulted in improved perioperative outcomes. More aggressive glycemic control (80
      120 mg/dL) provides no added improvement in CABG patients with less than or equal
      to 3 days of ICU care in the absence of ventilatory support or multiorgan
      failure. Although the precise value for achieving glycemic control in the
      perioperative period is the subject of much debate, the benefits of perioperative
      glycemic control with continuous insulin infusions in patients undergoing CABG is
      no longer debatable.

PMID- 22873043
TI  - Capillary leak syndrome in trauma: what is it and what are the consequences?
AB  - TICS is a complex disease that is clearly multifactorial in the traumatically
      injured patient (Fig. 2). Although systemic inflammation that occurs directly as
      a result of injury plays the most prominent role, the local tissue and organ
      injury effects of trauma not only cause local capillary leak and edema but also
      further amplify the SIRS response. High volume fluid administration and
      hypoproteinemic states further exacerbate the problem. All of this leads to organ
      dysfunction and failure, which is the third leading cause of death following
      injury. Strategies to treat TICS and attenuate its effects once it occurs by
      targeting inflammatory pathways have been wholly unsuccessful. The mainstay of
      therapy for TICS is prevention and minimization of its lethal effects. Newer
      resuscitation strategies such as hemostatic resuscitation and early goal-directed
      therapies are currently the best available strategies to combat TICS. Whether
      these result in better outcomes remains to be seen and the authors anxiously
      await the results of well-designed prospective trials.

PMID- 22873044
TI  - Morbidity and effectiveness of laparoscopic sleeve gastrectomy, adjustable
      gastric band, and gastric bypass for morbid obesity.
AB  - LSG, LAGB, and LRYGB are all safe and effective modern surgical options for the
      treatment of morbid obesity. Recent quality improvement successes in bariatric
      surgical care delivery have resulted in low mortality and morbidity after these
      procedures. All seem to result in sustained weight loss and improvement in weight
      related comorbidities, although appropriate long-term outcomes data for all
      procedure types are needed. The LRYGB seems to be associated with the most risk
      but offers the most benefit, whereas the LAGB seems to have the lowest risk and
      to be least effective. The LSG seems to be positioned between the LRYGB and LAGB
      in associated morbidity and effectiveness in short-term and medium-term studies.
      Because the LSG has only recently been performed, there are currently no data
      about its long-term effectiveness. A better understanding of the unique
      risk/benefit profile associated with each procedure type will better inform
      patient selection and has the potential to further optimize outcomes.

PMID- 22873045
TI  - Are cancer trials valid and useful for the general surgeon and surgical
      oncologist?
AB  - Cancer trials represent a rigorous and clear approach to testing whether an
      intervention or treatment will alter the outcomes of individuals with cancer in
      an experimental manner that is beyond the level of observational studies. As
      such, they remain useful and valid to the day-to-day practice of general surgeons
      and surgical oncologists. However, the shortcomings of current cancer clinical
      trials need to be recognized, especially when less than 1% of adults persons with
      cancer participate in cancer clinical trials, thus leaving the ability to
      generalize these trials to patients and their surgeons in the real-world setting
      an open question. Moving forward, physicians, payers, professional societies,
      advocates, the NCI, and other stakeholders need to develop broader cancer trials
      to benefit the millions of patients with cancer in the United States.

PMID- 22873046
TI  - The current management of pancreatic neuroendocrine tumors.
AB  - PanNETs constitute a rare and heterogeneous group of pancreatic neoplasms whose
      overall prognosis is better than the more common pancreatic adenocarcinoma.
      Although surgery is the only treatment that provides a cure, many adjuvant
      therapies have been explored with some new, exciting, targeted therapies just
      approved for PanNETs. With growing interest in this type of neoplasm, an
      increasing number of clinical trials and natural history studies should shed
      light on the best management for these patients.

PMID- 22873047
TI  - [Reactive nitrogen and oxygen species metabolism in rat heart mitochondria upon
      administration of NO donor in vivo].
AB  - Some aspects of reactive nitrogen and oxygen species (RNS and ROS) metabolism in
      rat heart mitochondria under administration of different doses of nitroglycerine
      (NG) in vivo are discussed. It is shown that NG administration results in a dose
      dependent increase in Ca2+-uptake in mitochondria, due to the dose-dependent
      inhibition of mitochondrial permeability transition pore (MPTP) in vivo and the
      activation of Ca2+-dependent mitochondrial NOS. It was shown that NOS activity
      increases in accord with the increase of Ca2+-uptake in mitochondria. The dose
      dependent activation of nitratreductase is observed. However, nitrite production
      decreases dose-dependently, according to the change of NO2-/NO3- ratio on behalf
      of NO3-, the end product of NO transformations. The relation between
      nitrosylation of mitochondrial proteins with the nitrosothiols formation and
      nitrate production also changes towards NO3-, which shows the activation of
      oxidation reactions in heart mitochondria after NG administration. Accordingly,
      dose-dependent increase in lipid peroxidation (LP) products is shown, the
      hallmark of the membrane damage in mitochondria. It is established that the cause
      of oxidative stress, besides the dose-dependent increase in ROS production
      (hydroperoxide, superoxide and hydroxyl-radical), lies in the increase of free
      iron content, derived from the oxidation of mitochondrial iron-containing
      proteins. The iron interaction with hydroperoxide following Fenton reaction as
      well as free-radical decomposition ofperoxynitrite, derived from NO3- are the
      possible cause of manifold increase in ROS as well as LP production, and RNS
      oxidation to NO3-. Thus, NO-dependent MPTP blockage, due to NO synthesis in
      mitochondria in vivo, results in the activation of both constituents of NO-cycle:
      NOS-dependent, due to Ca2+-dependent activation of mitochondrial NOS, and nitrate
      reductase-dependent, due to the increase in NO3- formation. However, increase in
      ROS production, augmented by the iron release, leads to the oxidative stress and
      the shift of RNS metabolism towards NO3- formation, in spite of the activation of
      nitrate-reductase-dependent pathway of NO-cycle. It is shown that reversible MPTP
      opening in vitro diminishes ROS production, whereas MPTP blockage by cyclosporine
      A restores the ROS formation to control level. Thus, MPTP-dependent inhibition of
      ROS overproduction both in vitro and in vivo, shows the importance of MPTP in the
      regulation of ROS and RNS metabolism in mitochondria.

PMID- 22873048
TI  - [Study of the impact of omega-3 PUFA on fatty acid composition of heart,
      respiration and swelling of mitochondria of the heart in diabetes].
AB  - We studied the influence of omega-3 polyunsaturated fatty acids (PUFAs) on
      respiration, swelling of rat heart mitochondria and changes in rat heart fatty
      acid composition in tissue homogenate in rats with streptozotocin induced
      diabetes mellitus (diabetes), which was induced by single intraperitoneal
      administration of 55 mg/kg streptozotocin. We found that application of these
      acids increased parameters of active mitochondrial respiration V3 at 63.7%,
      controlled breathing V4 at 30.7% and the rate of phosphorylation by 18.9% in
      animals with experimental diabetes. We proved their ability to reduce swelling of
      mitochondria in heart at streptozotocin induced diabetes. In addition, we
      established changes of fatty acid composition of cell membranes in hearts under
      diabetic conditions with omega-3 PUFAs influence. The obtained results allow to
      conclude that the omega-3 PUFA have a positive effect on functional parameters of
      mitochondria due to stabilization cell membranes of rat heart with diabetes.

PMID- 22873049
TI  - Expression of TNF-alpha mRNA, but not of TNF-alpha receptors mRNA, is detected in
      single murine oocyte and decreases during oocyte meiotic maturation: single-cell
      RT-PCR data.
AB  - BACKGROUND: The present study was conducted to investigate the expression of TNF
      alpha and its receptors (types I and II) in both oocytes with germinal vesicle
      and the first polar body in mice. METHODS: Oocytes with intact germinal vesicle
      were isolated from mouse ovaries and subjected to in vitro maturation to obtain
      oocytes forming the first polar body. A reverse transcription polymerase chain
      reaction (RT-PCR) was used to examine the expression of TNF-alpha and its
      receptors at mRNA level. RESULTS: mRNA TNF-alpha was expressed in single oocytes
      and its level was decreasing during transition from germinal vesicle to the first
      polar body stage. At the same time the expression of TNF-receptors was not
      observed in single oocyte. CONCLUSIONS: These data are the important link in
      understanding of the molecular mechanisms regulating oocyte maturation as well as
      follicle development.

PMID- 22873050
TI  - [Pioglitazone, an activator of PPAR-gamma, reduces the expression of kB nuclear
      factor and inhibits apoptosis in mononuclear cells of peripheral blood in vitro].
AB  - In order to examine the impact of PPAR-gamma activator on the expression of kB
      nuclear transcription factor and apoptosis, the peripheral blood mononuclear
      cells (PBMC) were incubated with pioglitazone at concentrations 10, 30 and 100
      MM. Expression of NF-kB in CD64+ cells was evaluated by flow cytometry using
      monoclonal antibodies. The development of apoptosis was evaluated using annexin V
      and propidium iodide. Activation of PPAR-y resulted in a reduction of the number
      of CD64+ cells and expression of the maximum levels of these receptors. We also
      obesrved a dose-dependent decrease of NF-kB concentration in PBMC suspension and
      in CD64+ cells. While analyzing the apoptosis, the reduction of apoptotic cells
      (reduction of AnV+PI+ cells) has been observed. The results obtained allow to
      prove that PPAR-gamma activation participates in the PBMC apoptosis regulation
      and in the expression of transcriptional factor NF-kB. Our results indicate for
      the involvement of PPAR-gamma in the regulation of NF-kB activity which plays one
      of the most significant roles in the inflammation realization, oncogenesis, and
      so on.

PMID- 22873051
TI  - Effect of tilorone and its analogues on the change of mitochondrial potential of
      rat hepatocytes.
AB  - The influence of tilorone dihydrochloride and its analogues--diphenyl derivatives
      on the changes of transmembrane potential of mitochondrial membranes of the
      isolated rat hepatocytes has been estimated. Authors have shown a significant
      increase in mitochondrial potential thirty minutes after the introduction of the
      test compounds to the cells using the fluorescent probe JC-1. These results
      indicate the rapid activation with tilorone and its analog--dihydrochloryde 4,4'
      bis-[2-(diethylamino)ethoxy]diphenyl--of the RLR signaling pathway. The final
      stage of this pathway is the cell production of IFN type I. The authors concluded
      that there is an increasing of the organelles resistance to the
      extra/intracellular damaging agents under the influence of the test compounds.

PMID- 22873052
TI  - [The influence of autologous umbilical cord blood and donor blood on cytokine
      profile of newborns with transposition of great vessels].
AB  - We investigated the serum levels ofproinflammatory and antiinflammatory cytokines
      (TNF-alpha, IL-1beta, IL-6, IL-8, IL-10) in newborns with transposition of the
      great arteries to whom during the defect correction the autologous umbilical cord
      blood and blood components were administered before the surgery and at the 1st,
      3rd, 7th day after the surgery. We found that in the group of newborns to whom
      during the operation the blood components were used, the levels ofpro
      inflammatory interleukins were high before surgery and at the Ist, 3rd and 7th
      day after it, but IL-10 was reduced. During the postoperative period, the
      newborns of this group had imbalance in the system cytokine, accompanied by
      clinical complications such as hyperthermia and pulmonary complications. Newborns
      with transposition of the great arteries who had the surgery using the autologous
      cord blood, had no significant abnormalities in serum levels cytokine before the
      surgery. The Ist day after surgery there was an increase in both proinflammatory
      and antiinflammatory cytokines. Up to 7 days the levels of interleukin gradually
      decreased. Newborns in this group had no postoperative complications, had an
      adequate immune response to the operation.

PMID- 22873053
TI  - [Normobaric hyperoxia affects osteogenesis in rats].
AB  - We studied the influence of normobaric hyperoxia on bone metabolism in 3- and 12
      month-old male Wistar rats. Maintaining young rats (3 months) during the 14-hour
      daily sessions under normobaric hyperoxia (90% O2) was accompanied by a
      significant decrease in the concentration of C-terminal propeptides of collagen
      type I (by 36%), the acid phosphatase activity (by 32%), an increased activity of
      alkaline phosphatase (by 64%), an increased concentration of pyridinoline (by
      37%) and 3-CrossLaps (by 8%), glycosaminoglycans (by 72%) in the blood serum. We
      believe that normobaric hyperoxia (90%) is accompanied by the disturbance of
      collagen synthesis. In adult rats under the same conditions for 14 sessions, the
      concentration ofglycosaminoglicans significantly increased by 60% relative to the
      control values. After 28 sessions of breathing the normobaric gas mixture
      containing 90% O 2 this parameter increased by 195%. Breathing normobaric gas
      mixture containing both 40% and 90% of O2 for 14 and 28 days decreased the acid
      phosphatase activity and the tartrat-resistant acid phosphatase activity by 18
      25%. We believe that in adult animals 90% hyperoxia does not affect the activity
      of osteoblasts, but breaks the link between glycosaminoglicans and collagen
      fibrils, decreases the activity oflysosomal enzymes which are produced by
      osteoclasts and which can inhibit osteogenesis.

PMID- 22873054
TI  - [The influence of long-term monosodium glutamate feeding on the structure of rats
      pancreas].
AB  - The influence of prolonged administration of monosodium glutamate (MSG) on
      pancreas in rats was studied. It was established that 30-days feeding by MSG in
      the doses 15 to 30 mg/kg (equivalent to 1 and 2 g/person) leads to necrotic,
      necrobiotic and degenerative changes in exocrine and endocrine cells, leukocytic
      and lymphoid infiltration, perivascular and interstitial fibrosis, edema and
      discirculatory disorders. Introduction of sodium glutamate increases the cross
      sectional area of nuclei ofexocrine and endocrine cells, indicating
      intensification of synthetic processes in the cells of the pancreas and reduces
      the cross-sectional area of exocrine pancreatic cells, which is a sign of
      stimulation of secretory processes in exocrine cells. The changes described are
      characteristic of the acute pancreatitis. It is concluded that the maximum daily
      dose of food supplements containing glutamic acid and its salts should be
      reviewed because of their adverse effects on the pancreas. It is concluded that
      the maximum dose of MSG should be reconsidered taking into account its influence
      on the pancreas.

PMID- 22873055
TI  - [Contraction properties and musculo-tendinous stiffness of the human triceps
      surae muscle and their change as a result of a long-term bed-rest].
AB  - The effect of a 120-day 5 degree head-down tilt (HDT) bed rest on the mechanical
      properties and electromechanical delay (EMD) of the human triceps surae (TS)
      muscle was studied in four (mean age 31.5+/-1.7 yr) healthy young women subjects.
      The TS mechanical properties were evaluated based on the following indicators:
      maximal voluntary contraction (MVC), maximal strength (Po; frequency 150 Hz),
      peak twitch force (Poc), time-to-peak tension (TPT), half-relaxation time (1/2
      RT) and tension development time to reach 25, 50, 75 and 90% of maximal tension.
      Force deficit (Pd) were estimated. In response to a light signal,the subject was
      supposed to make a voluntary foot flexion, with the instruction "to exert the
      fastest and greatest tension". EMD measurements were recorded from each subject
      during voluntary contraction. Surface electrodes sensed electromyographic (EMG)
      activity in the soleus muscle. A separate timer was used to determine total
      reaction time (TRT). Premotor time (PMT) was taken to be the time interval from
      the delivery of the signal to change in EMG. EMD was the time interval between
      the change in EMG and movement i.e. the time interval between EMG and the onset
      of muscle tension. After HDT Poe, MVC and Po decreased by 24.4, 36.1 and 11.5%,
      respectively, while Pd increased by 38.8%. TPT increased by 13.6%, while 1/2RT
      decreased by 19.2%. The rate of increase of voluntary contractions calculated
      according to a relative scale significantly increased, while the rate of
      development of electrically evoked contraction did not show any significant
      differences. The voluntary contraction EMD increased by 27.4%; PMT by 8.7%, and
      TRT by 13.6%. Thus, the mechanical changes suggest that weightlessness changes
      not only the peripheral processes associated with contractions but also the
      central and neural command. EMD is a simple and quick method for evaluation of
      muscle stiffness changes. Moreover, EMD can serve as an indicator of the
      functional condition of the neuromuscular system.

PMID- 22873056
TI  - [Age peculiarities of cerebral hemodynamics in visually impaired children of
      preschool and primary school age].
AB  - 149 visually impaired children (including 75 preschoolers and 74 junior pupils)
      and 159 healthy children of the first- second group of health (including 79
      preschoolers and 80 elementary school children) were examined by the method of
      REG with using fronto-mastoidal and occypito-mastoidal recordings. Cerebral
      hemodynamics in impaired children, keeping the age patterns, has features of
      reduced blood volume and blood flow velocity. These changes were accompanied by
      an increased tone of arterial and venous vessels of small caliber and peripheral
      vascular resistance, which becomes more prominent as children get older. These
      features of cerebral circulation were more pronounced in the vertebro-basilar
      area compared to the carotid area, and in right hemisphere compared with the left
      hemisphere. Age-related changes of cerebral hemodynamics are to increase the
      dicrotyc and diastolic indices and peripheral vascular resistance during the
      transition from preschool to primary school age, which is related to
      restructurization of cerebral vessels. Visually impaired children have a greater
      increase in these age indices compared with healthy children.

PMID- 22873057
TI  - [Hypoxic pulmonary hypertension: modern views on pathogenesis and options for
      rational pharmacological correction].
AB  - In the article, an analysis of the modern approaches to pharmacological
      correction of hypoxic pulmonary hypertension in conjunction with its development
      mechanisms has been performed. Promising research trends for the creation of new
      drugs in this field have also been reviewed.

PMID- 22873058
TI  - [Il'a Faddeevich Tsion--pioneer of vestibular physiology].

PMID- 22873059
TI  - [Variation of vector potential in laboratory conditions changes biological
      properties of water].
AB  - It was found that water preliminary activated with vector potential changes
      mobility of infusoria, bringing into it, the rate of sugar fermentation in yeast
      cells and a drinking attractivity of water for mice. It was also shown that water
      physical parameters changed after water activation: UV absorptions spectrum and a
      state of a silica admixture. It was supposed that water is the initial target
      when weak electromagnetic fields have an influence on biological objects.

PMID- 22873060
TI  - [The internal cavities of pike alpha-parvalbumin probably contain water].
AB  - The kinetics of hydrogen exchange of pike a-parvalbumin was investigated using
      the method of infrared spectroscopy (sensitive to the amide hydrogen atoms in the
      peptide) and radioisotope method (sensitive to all labile hydrogen atoms).
      Ultraslow exchangeable hydrogen atoms were found to be substantially less in the
      first case than in the second one. Taking into account that the internal cavities
      in the parvalbumin are formed by hydrophobic amino acid residues, devoid of
      labile hydrogen atoms, it is possible to make the most appropriate assumption,
      namely, these cavities contain water molecules, hydrogen atoms of which are
      ultraslow exchangeable.

PMID- 22873061
TI  - [Association of gold nanorods in water solutions: influence of globular
      proteins].
AB  - By absorption spectroscopy method optical properties of gold nanorods (10x38 nm)
      and their interaction with globular protein bovine hemoglobin and bovine serum
      albumin were investigated. Nanorods behavior was studied in water solution and in
      solution of 97 mM NaCl under ultrasound action during 90 min and results were
      then compared. In water solutions nanorods coagulation (aggregation) was observed
      with reduced optical density of the longitudinal plasmon band widening at
      lamda>800 nm. In NaCI solution absorption spectra evolution had complex character
      and was in some degree analogous to the result that was obtained for two
      dimensional grids of gold nanoparticles when changing the distance between them.
      By interacting with serum albumin stabilization of colloid solution and
      dissociation of nanorods aggregates were observed.

PMID- 22873062
TI  - [K-35, a fluorescent probe for albumin study: optical properties].
AB  - Fluorescent probe N-(carboxyphenyl)imide of 4-(dimethylamino)naphthalic acid, K
      35, is used as an indicator of structural changes of human serum albumin
      molecules in pathology. The probe occupies albumin binding pockets where the
      probe environment is of very high polarity; probably, the pocket(s) contains
      protein polar groups and water molecules. At the same time rather small Stokes
      shift of K-35 fluorescence spectrum shows that the polar group motion is of one
      two order of value lower than mobility of polar molecules in polar fluids. K-35
      fluorescence decay in HSA can be described as a sum of three exponentials with
      time constants close to tau1=9 ns; tau2=3.6 ns and tau3=1.0 ns. A difference
      between excitation maxima of these three decay components shows that environment
      of these three species of K-35 molecules has been different before excitation.
      Different r values are probably a consequence of non-identical structure of
      several binding sites, or a binding site(s) can have a variable conformation.

PMID- 22873063
TI  - [Spectral and functional properties of ceruloplasmin under UV irradiation].
AB  - During oxydase reaction spectral characteristics of ceruloplasmin at absorption
      of copper ions and protein part of the molecule are shown to change. It has been
      ascertained, that when irradiating ceruloplasmin by UV-light the functioning of
      intramolecular electron transport chain is broken, the degree of positive
      cooperativity (a Hill's constant) on substrate decreases. It is supposed, that
      these changes are caused by disturbance of interdomain interactions in a protein
      molecule.

PMID- 22873064
TI  - [Antiamyloid properties of fullerene C60 derivatives].
AB  - A comparative estimation of the ability of complexes of fullerene C60 with
      polyvinylpyrrolidone and fullerene C60 derivatives (the sodium salt of the
      polycarboxylic derivative of fullerene C60, sodium fullerenolate), has been
      carried out. The fullerenes destroyed amyloid fibrils of the Abeta(1-42) peptide
      of the brain and the muscle X-protein. A study of the effect of fullerenes on
      muscle actin showed that complexes of fullerene C60 with polyvinylpyrrolidone and
      sodium fullerenolate did not prevent the filament formation of actin, nor did
      they destroy its filaments in vitro. Conversely, sodium salt of the
      polycarboxylic derivative of fullerene C60 destroyed actin filaments and
      prevented their formation. It was concluded that sodium fullerenolate and
      complexes of fullerene C60 with polyvinylpyrrolidone are the most effective
      antiamyloid compounds among the fullerenes examined.

PMID- 22873065
TI  - [Model of cytosine-, thymine-containing olygodeoxyribonucleotide protonation in
      solution].
AB  - In the present study, the experimental data on the pH-induced formation of the i
      motif structure in the nucleotide sequence 5'-CCTTTCCTTTTCCTTTCC-3' (25oC, pH 3.3
      8.9) obtained by spectroscopic techniques, such as UV molecular absorption and
      circular dichroism, has been analysed using the chemometric soft modelling-based
      MCR-ALS approach and the hard modelling-based matrix method. Soft modelling using
      2 or 3 spectral species correctly reproduced spectral variations observed
      experimentally. The use of hard chemical modelling enabled us to propose the
      equilibrium model, which describes spectral changes as functions of solution
      acidity. Additionally, the intrinsic protonation constant Kin, and the
      cooperativity parameter w have been calculated from the fitting procedure of the
      circular dichroism as well as molecular absorption spectra. The results indicated
      that folding was accompanied by a cooperative process, i.e. the enhancement of
      protonated structure stability upon protonation.

PMID- 22873066
TI  - [Investigation of site-specific DNA binding with nicking endonuclease Nt.BspD6I
      at single molecule level by atomic force microscopy].
AB  - Nicking endonuclease Nt.BspD6I is a heterodimeric restriction endonuclease, one
      subunit of which exhibits specific nicking activity. It gets bound to double
      stranded DNA and makes a break (nick) in one chain at a distance of 4 nucleotides
      from the binding site. In this work, for visualization of the specific binding
      and protein landing site an atomic force microscopy was used. In five minutes
      after incubation of DNA solution with nicking endonuclease, the DNA molecules
      with associated proteins which located at the expected binding site and "shared"
      DNA strand into two segments (approximately, 1/3 and 2/3 of length) were observed
      in the images. In addition, near the binding site DNA molecule had a height
      corresponding to a single-stranded DNA molecule, which was in good agreement with
      single-stranded cleavage by nickase in the course of complex formation.

PMID- 22873067
TI  - [Effects of several inhibitors of intracellular signaling on production of
      cytokines and signal proteins in RAW 264.7 cells cultivated with low dose
      ammonium].
AB  - Effects of four inhibitors of NF-kappaB, SAPK/JNK and TLR4 signaling, namely,
      inhibitor XII, SP600125, CLI-095 and Oxpapc on a macrophage response to low dose
      ammonium were studied in RAW 264.7 cells. Low dose ammonium induced pro
      inflammatory response in cells as judged from enhanced production of TNF-alpha,
      IF-gamma, and IL-6, and by activation of signal cascades. The increase in
      production of cytokines, namely TNF, IFN, and IL-6, demonstrated that low-dose
      ammonium induced a pro-inflammatory cellular response. In addition, an activation
      of NF-kappaB and SAPK/JNK cascades, as well as enhancement of TLR4 expression was
      shown. Each of used inhibitors reduced to a variable degree the pro-inflammatory
      response of RAW 264.7 cells on chemical toxin by decreasing cytokine production.
      The inhibitor of NF-kappaB cascade, IKK Inhibitor XII, was more effective, and
      not only prevented the development of pro-inflammatory response induced by
      ammonium, but also decreased cytokine production below control values. The
      inhibitor of extra cellular domains of TLR2 and TLR4 (OxPAPC) had almost the same
      anti-inflammatory effect, and an addition of the inhibitor of JNK cascade
      (SP600125) to cell culture practically neutralized effect of ammonium ions by
      decreasing cytokine production to control level. Inhibitory analysis showed that
      activation of RAW 264.7 cells induced by chemical toxin coincide incompletely
      with intracellular signaling pathways that were early determined regarding
      macrophage's response to toxin from gram-negative bacteria. Nevertheless,
      application of the inhibitors defended RAW 264.7 from toxic effect of the low
      dose ammonium.

PMID- 22873068
TI  - [ROS induction and structural modification in human lymphocyte membrane under the
      influence of carbon nanotubes].
AB  - To assess the potential risks of using the artificial nanostructures the
      structural state of the human lymphocyte membrane and lipid peroxidation under
      the influence of multi-walled carbon nanotubes with metal impurities was studied.
      The ability of carbon nanotubes to induce the formation of reactive oxygen
      species in cells was examined. A dose-dependent increase in reactive oxygen
      species formation in lymphocytes, which was not registered in cells pre-incubated
      with N-acetylcystein, after exposure to carbon nanotubes was shown. The addition
      of iron chelator deferoxamine to carbon nanotubes has also resulted in a decrease
      of reactive oxygen species. The mechanism of the activation of lipid peroxidation
      under the influence of carbon nanotubes and a structural modification of human
      lymphocyte membranes were discussed.

PMID- 22873069
TI  - [Y-27632 induces calcium-independent glutamate release in rat brain synaptosomes
      by the mechanism which is distinct from exocytosis].
AB  - The inhibitor of Rho-kinase Y-27632 induces non-secretory exocytosis in PC12
      cells. The influence of this compound on central synapses remains uninvestigated.
      We showed that Y-27632 at the concentration 100 jtM led to spontaneous
      [14C]glutamate release in synaptosomes, which was not accompanied by plasma
      membrane depolarization. Membrane potential was registered by fluorescent dye
      DiSC3(5). Y27632 induced an increase of acridine orange fluorescence, exercising
      no influence over fluorescence of FM2-10 dye. These results suggest that Rho
      kinase inhibition decreases pH gradient of synaptic vesicles not inducing
      exocytosis. Dissipation of the gradient leads to leakage of neurotransmitters to
      cytosol pumping them out by plasma membrane transporters. Our results show the
      involvement of Rho-dependent branch of intracellular signaling in regulation of
      pH gradient in synaptic vesicles.

PMID- 22873070
TI  - [Obtaining the phage mini-antibodies and their use for detection of microbial
      cells by using an electro-acoustic sensor].
AB  - The phage mini-antibodies to bacterial cells of strain Azospirillum brasilense
      Sp245 were obtained and the possibility of using them for detection of microbial
      cells by means of a lateral field excited piezoelectric resonator was studied. It
      has been found that the frequency dependencies of the real and imaginary parts of
      the electrical impedance of the resonator loaded by the cell suspension A.
      brasilense Sp245 with the mini-antibodies, significantly differ from those of the
      resonator with the control cell suspension without mini-antibodies. The
      concentration limit of possible determination of the microbial cells in their
      interaction with the mini-antibodies is equal to 10(3) cells/ml. It has been
      ascertained that detection of A. brasilense Sp245 cells using the mini-antibodies
      is possible even in the presence of other cultures, for example, E. coli BL-Ril
      and A. brasilense Sp7 cells. Therefore, it has been shown for the first time that
      detection of microbial cells by an electro-acoustic sensor is feasible.

PMID- 22873071
TI  - [Effect of different water-soluble forms of the fullerene C60 on the metabolic
      activity and ultra-structure of cells in culture].
AB  - In view of contradictory data on the toxicity of fullerenes for live organisms we
      studied the effect of water-soluble complexes of C60 with N-polyvivyl-pirrolidone
      (C60/PVP) and gamma-cyclodextrine (C60/gamma-CD) on MA-104 cells in culture. Both
      complexes proved to be non-toxic for cultured cells in the dark in wide range of
      concentrations. Both complexes provoke changes of cellular ultra-structure which
      reflect the enhancement of metabolic activity. At the same time only the
      exposition with the complex C60/PVP leads to the essential growth of number and
      size of mitochondria. However, the effect of two studied water-soluble forms of
      C60 under intensive UV-irradiation of cells proved to be opposite: C60/PVP had a
      cyto-protective action while C60/gamma-CD caused a significant growth of photo
      toxicity. Possible reasons of the differences in the action of different forms of
      C60 on living organisms are discussed.

PMID- 22873072
TI  - [Extremal principles and goal functions of biocoenotic systems].
AB  - A review considers known in the ecology two alternative principles of maximizing
      or minimizing the diversity-entropy of biological systems, and shows the
      inadequacy of both extremal principles in application to natural biocoenotic
      assemblages. A necessary condition for the multispecific system's existence is
      not extremization any of their parameters, but optimization of the relations of
      their parameters (including those that uniquely determine the value of species
      diversity). Thus, the goal function, which tends to minimize any biocoenotic
      system in the course of succession and evolution, is a deviation from this
      optimal ratio.

PMID- 22873073
TI  - [The impact of population dynamics on Y-chromosome microsatellite Polymorphism.
      Mathematical modeling].
AB  - In this article, we use mathematical modeling to study the impact of population
      dynamics on Y-chromosome STR-polymorphism accumulation in two independently
      evolving populations, namely, on the changes in genetic distance among the
      populations. Using two definitions of the genetic distance: (deltamu)2 and ASD,
      we carry out comparative research on the genetic distance changes and show that
      in contrast to (deltamu)2, ASD is characterized by a near-linear dependence on
      time. As the populations undergo oscillations, ASD is shown to be smaller than
      that in stationary populations. The linear dependence of ASD on time is shown to
      break down in relatively scanty stationary populations.

PMID- 22873074
TI  - [On electric potential along the plant stem].
AB  - Electric potential difference along the stem of Pelargonium zonale plant has been
      measured. Three relaxation time values have been established. They correspond to
      different types of interelectrode space polarization (ion, ion-molecular,
      combined molecular-associative).

PMID- 22873075
TI  - [Mathematical modeling of ventricular disturbances following atrial
      fibrillation].
AB  - The present study presents the results of mathematical and computer modeling of
      atrial fibrillation and ventricular disturbances following atrial fibrillation.
      The model is based on the assumption, that electric impulsation arriving on the
      atrioventricular node during atrial fibrillation is sum N of independent pulse
      streams with various amplitude-frequency and phase characteristics. With this
      model it becomes possible to investigate the dependence of nonlinear dynamics of
      PP and RR intervals on amplitude-frequency and phase characteristics pulse
      streams. Results of computer experiments are compared with real physiological
      experiments on rabbits. Identification of model was carried out by means of least
      squares procedure.

PMID- 22873076
TI  - [Parameters of fibers cell respiration and desmin content in rat soleus muscle at
      early stages of gravitational unloading].
AB  - The aim of the work was to study the parameters of fibers cell respiration and
      desmin content in Wistar rat soleus muscle after 1, 3, 7 and 14 days of
      gravitational unloading. Gravitational unloading was simulated by antiorthostatic
      hindlimb suspension. The parameters of cell respiration were determined using the
      polarography, and desmin content was assessed by means of Western blotting. The
      results showed that the intensity of cell respiration is reduced after three days
      of gravitational unloading, reaches a minimum level after seven days and slightly
      increases by the fourteenth day of hindlimb unloading, as well as the content of
      desmin, which, however, to the fourteenth day returns to the control level.
      Taking into account that mitochondrial function depends on the state of
      cytoskeleton the data allow us to assume that early reduction of the intensity of
      cell respiration under unloading could be caused by degradation of the protein
      desmin that determines intracellular localization of mitochondria.

PMID- 22873077
TI  - [Heliogeophysical correlates of early biodemographic variables in the south of
      western Siberia].
AB  - In order to verify associations between solar and geomagnetic activities and
      perinatal variables the monthly distributions of population characters in
      Novosibirsk region over the period 1980-2001 were compared by stepwise
      correlation analysis with monthly averaged physical parameters at lags from 0 to
      10 months. Three indices used were as follows: the number of sunspots, solar flux
      at 10.7 cm wavelength and Ak index measured at local ionospheric station near
      Novosibirsk city. Official data on the number of single and multiple live births,
      stillbirths and infant deaths at the age under one year by the type of population
      and sex were provided by State Statistical Committee. All three physical
      parameters positively correlated with the number of single births and infant
      mortality rate and negatively with twin births in both populations, urban and
      rural, irrespective of lags. The direct association between Ak index and relative
      number of stillbirths in urban setting was mostly pronounced at a lag of 5
      months. The number of live births increased along with Ak index due to the
      enhanced proportion of female births whereas the number of stillbirths after the
      increase in solar and geomagnetic activities elevated because of male deaths.

PMID- 22873078
TI  - [Biophysical methods for biochip analysis. Use of wide field digital fluorescent
      microscopy].
AB  - This paper discusses an issue on the development of biophysical methods for
      biochip analysis. A scheme and construction of a biochip analyzer based on wide
      field digital fluorescence microscopy are described. The analyzer is designed to
      register images of biological microchips labeled with fluorescent dyes. The
      device developed is useful for high-sensitive throughput recording analyses by
      biochips after interaction of immobilized probes with fluorescently labeled
      sample molecules as well as it provides the higher rate of the analysis compared
      to laser scanning devices. With this analyzer a scope where biological microchips
      can be applied becomes wider, the development of new protocols of the analyses is
      possible and standard analyses run faster with the use of biochips, the expenses
      for the analysis performance can be reduced.

PMID- 22873079
TI  - [Invariants of the anthropometrical proportions].
AB  - In this work a general interpretation of a modulor as scales of segments
      proportions of anthropometrical modules (extremities and a body) is made. The
      objects of this study were: 1) to reason the idea of the growth modulor; 2) using
      the modern empirical data, to prove the validity of a principle of linear
      similarity for anthropometrical segments; 3) to specify the system of invariants
      for constitutional anthropometrics.

PMID- 22873080
TI  - Controversial cancer screening guidelines can help nurses start the screening
      conversation.

PMID- 22873081
TI  - Keeping up with cancer screening guidelines.

PMID- 22873082
TI  - What guidelines are used for follow-up care for cancer survivors?

PMID- 22873083
TI  - Manage malnutrition in patients with chemotherapy-induced nausea and vomiting.

PMID- 22873084
TI  - The case of the phone in the freezer.

PMID- 22873085
TI  - Tobacco kills more than 1200 Americans a day. ONS teams up with NCPF and others
      for cessation strategies.

PMID- 22873086
TI  - Is thermography or mammography a more effective breast cancer screening tool?

PMID- 22873087
TI  - New drugs help immune system fight cancer.

PMID- 22873088
TI  - What's in your ONS profile, and why does it matter?

PMID- 22873089
TI  - Nursing experience and certification pay off.

PMID- 22873090
TI  - Frequency of recurrence after surgical treatment of cervical intraepithelial
      neoplasia grade 1-3.
AB  - PURPOSE OF INVESTIGATION: The objective was to demonstrate the frequency of
      invasive cervical cancer or recurrent CIN in patients treated by a previous
      diagnosis of CIN 1-3. METHODS: We analyzed 1,397 records colpocytologic and
      medical records. Recurrence of CIN or invasive neoplasia of the cervix after
      treatment of CIN was assessed. The chi-square test was used for statistical
      analysis (significance level set at less than 0.05). RESULTS: We obtained 696 CIN
      1, 244 CIN 2, 451 CIN 3, and six squamous carcinoma. Regarding patients who
      relapsed, there were 6/690 (0.9%) patients had an initial diagnosis of CIN 1,
      8/236 (3.4%) CIN 2 and 21/430 (4.9%) CIN 3 (p < 0.0001). Comparing the frequency
      of relapse among each group, we found: CIN 1 vs CIN 2: p = 0.0073; CIN 1 vs CIN
      3: p < 0.0001; CIN 2 vs CIN 3: p = 0.38. CONCLUSION: Although the number of
      relapses when comparing CIN 2 and CIN 3 were not significant, the data suggest
      that CIN 2 has lower recurrence rates, so these patients require more
      conservative treatment if a desire of future pregnancy is expressed.

PMID- 22873091
TI  - Effect of cryotherapy and povidone-iodine preparation on eradication of DNA
      corresponding to highly oncogenic HPV in women with lesions in the uterine
      cervix.
AB  - In all 88 patients, 23-67 years of age (mean of 34.8 years) with abnormal
      cytology, lesions in the uterine cervix and presence of DNA corresponding to
      highly oncogenic HPV, two cycles of uterine cervix cryotherapy and local
      treatment with povidone-iodine resulted in eradication of the virus six months
      after detection of the virus.

PMID- 22873092
TI  - Chemotherapy-related hypersensitivity reaction in Japanese patients with
      gynecologic malignancy.
AB  - PURPOSE OF INVESTIGATION: Chemotherapy-related hypersensitivity reaction seems to
      be problematic in the safe management of chemotherapy. In this study we
      investigated chemotherapy-related hypersensitivity reaction in patients with
      gynecologic malignancy. METHODS: Between January 2009 and December 2010, we
      examined hypersensitivity reaction (> or = grade2) using the Common Terminology
      Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence, clinical
      features, management, and outcome. RESULTS: We administered over 1,057 infusions
      (24 regimens) to 205 patients. We found a total of four hypersensitivity
      reactions (> or = grade 2) cases (carboplatin: 2; nedaplatin: 1; docetaxel: 1).
      Signs and symptoms were varied. In two cases, the same regimen was rechallenged
      by using anti-allergic drugs. The docetaxel case was successful. The carboplatin
      case was not successful. CONCLUSION: Chemotherapy-related hypersensitivity
      reaction (> or = grade2) does not occur frequently. In the case of platinum,
      especially, carboplatin, re-administering after hypersensitivity reaction should
      be done carefully though platinum is a key drug in patients with gynecologic
      malignancies.

PMID- 22873093
TI  - Sentinel node biopsy in male breast carcinoma: is the "female" approach
      justified?
AB  - PURPOSE: Mastectomy with axillary lymph node dissection (ALND) represents the
      gold standard in the treatment of male breast carcinoma. Recently, data have
      emerged supporting that sentinel lymph node biopsy (SNB) may be feasible in
      selected patients. The aim of this study was to analyze the safety and prognostic
      reliability of SNB in male patients with breast carcinoma and clinically negative
      axilla. METHODS: During a 10-year period (2000-2010), 11 men with mean age 66.1
      years (range 34-84) diagnosed with breast carcinoma were retrospectively included
      to our study. All patients underwent SNB. Regardless of the SNB results,
      completion axillary clearance was conducted in all cases. RESULTS: SNB detection
      rate was 100%, while the mean number of sentinel nodes removed was 1.5 +/- 0.7
      (range 1-2). Frozen section analysis revealed a negative sentinel node in four
      out of 11 patients (36.4%). Independently of these results, all patients
      underwent completion ALND. The overall false-negative rate, defined as the
      percentage of all node-positive tumors in which the SNB was negative, was 0%.
      CONCLUSION: The current study indicates that SNB may be feasible in selected male
      individuals with breast carcinoma. The technique may reduce the morbidity related
      to dissection of the axilla; prospective multicenter trials are needed in order
      to define the exact criteria for wider application of this technique.

PMID- 22873094
TI  - Comparison of the efficacy and complications of different surgical methods for
      cervical intraepithelial neoplasia.
AB  - OBJECTIVE: The aim of this was study to offer some reference for the treatment of
      cervical intraepithelial neoplasia (CIN) by comparing complication rates and
      treatment failure rates of different surgical methods of CIN. METHODS: 1,256
      cases of CIN diagnosed by punch biopsy and pathological confirmation of
      postoperative specimens between January 2002 and June 2007 were reviewed and
      analyzed, in which 74 cases underwent the loop electrosurgical excision procedure
      (LEEP), 869 patients adopted cold knife conization (CKC), 49 patients received
      vaginal enlarged amputation of cervix, and 264 patients accepted extrafascial
      hysterectomy. The chi-square test was used to compare the rate of complication
      and treatment failure of different surgical methods. RESULTS: The rates of
      surgical complications for LEEP, CKC, vaginal enlarged amputation of the cervix
      and extrafascial hysterectomy were, respectively, 8.1% (6/74) 6.2% (54/869) 6.1%
      (3/49) and 2.3% (8/264), but this difference was not statistically significant.
      The treatment failure incidences for LEEP, CKC, vaginal enlarged amputation of
      cervix and external fascia hysterectomy were, respectively, 4.1% (3/74), 0.2%
      (2/869), 0.0% (0/49) and 0.4% (1/264). When comparing among the groups, the
      treatment failure incidence was higher in LEEP than that in CKC (p = 0.004) and
      extrafascial hysterectomy (p = 0.034); there was no statistically significant
      difference between CKC and extrafascial hysterectomy, and no significant
      difference was revealed between vaginal enlarged amputation of cervix and any
      other group. CONCLUSION: LEEP, CKC, vaginal enlarged amputation of cervix and
      extrafascial hysterectomy are all secure and effective procedures for patients
      with CIN, and patients can make their own individual choice depending on
      different conditions.

PMID- 22873095
TI  - "Low-grade positivity" of HPV viral load after atypical squamous cells of
      undetermined significance (ASC-US) cytology identifies women at low-risk for
      cervical intraepithelial neoplasia grade 2 and 3.
AB  - The correlation between high-risk HPV-DNA viral load, expressed as relative light
      units (RLU) values obtained from the Hybrid Capture 2 (HC2) test, and the
      prevalence of CIN2/CIN3 was investigated and statistically analyzed in 614 ASC-US
      consecutive cases. Cases were categorized into three groups according to RLU
      values: "low-grade positivity", "intermediate positivity" and "high-grade
      positivity", and the prevalence of CIN2/CIN3 was evaluated in the single groups
      and compared among them. CIN/CIN3 rates demonstrated a significant (p < 0.001)
      increase with a direct correlation with increasing RLU values: 4.6% (RLU from 1.0
      to 10.0), 9.1% (RLU from 11.0 to 100.0) and 32.2% (RLU > 100.0) respectively. The
      prevalence of CIN2/CIN3 between the group with RLU < 10.0 (4.6%) and the group
      with RLU > 10 (24.2%) showed statistical significance (p = 0.0002). Increasing
      hrHPV viral load significantly correlates with increasing prevalence of CIN2/CIN3
      in ASC-US cases.

PMID- 22873096
TI  - Correlation of cancer risk evaluation and early detection (CADET) scores with
      abnormal ultrasonographic ovarian findings.
AB  - OBJECTIVE: To determine the utility of a modified version of ovarian cancer
      focused cancer risk evaluation and early detection (CADET) scores as a screening
      tool for ultrasonographic ovarian findings. STUDY DESIGN: Prospective pilot
      study. MAIN OUTCOME MEASURES: CADET scores were compared with abnormal
      ultrasonographic ovarian findings of peri- and postmenopausal women who attended
      their gynecologist for a routine check-up. The women filled in the CADET
      questionnaire before seeing their gynecologists who were blinded to the CADET
      results. The women whom they referred for pelvic transvaginal ultrasonographic
      examination comprised the study group. The results of their scans were compared
      with their CADET scores. RESULTS: Of the 181 peri- and postmenopausal women who
      were candidates for this study, 154 were referred for ultrasonography, of whom 38
      (24%, Group A) had abnormal ovarian scans (30 simple cysts and 8 complex
      findings). The other 116 (76%) women had normal sonograms (Group B). Demographic
      characteristics were similar for both groups. Thirteen Group A women (34%) and 52
      Group B women (45%) had positive CADET scores (p = NS). The average group CADET
      scores were also not significantly different (0.8 +/- 1.7 for Group A and 1.7 +/-
      2.5 for Group B). CONCLUSION: CADET scores did not correlate with abnormal
      ultrasonographic ovarian findings.

PMID- 22873097
TI  - Normal serum CA125 half-life and normal serum nadir CA125 level in patients with
      ovarian cancers.
AB  - The normal serum CA125 half-life and distribution of the normal serum nadir CA125
      value in patients with epithelial ovarian carcinoma (EOC) have not been
      determined yet. Among patients with EOC, 41 patients met the inclusion criteria
      of the present study: the patients that underwent complete cytoreductive surgery
      and six cycles of platinum-containing chemotherapy, and who had no recurrent
      disease more than five years. Serum CA125 half-life (T1/2) during primary surgery
      and primary chemotherapy was calculated and serum nadir CA125 level was evaluated
      by logarithmic-transformed serum CA125. Median value of nadir CA125 was 7 U/ml
      (range 3-20 U/ml), and the mean ln (serum nadir CA125) was 1.96 +/- 0.45. Mean
      T1/2 was 10.4 days in all patients, and T1/2 value was associated with the
      preoperative serum levels of CA125. Predicted slope of CA125 regression curve was
      also influenced by the preoperative CA125 value. The present study provides
      fundamental information with regard to normal half-life time and normal nadir of
      CA125 in EOC patients.

PMID- 22873098
TI  - Expression of P-Akt, NFkappaB and their correlation with human papillomavirus
      infection in cervical carcinoma.
AB  - PURPOSE: To investigate the expression of P-Akt and NFkappaB and their
      correlation with human papillomavirus (HPV) infection in cervical carcinoma.
      MATERIAL AND METHODS: Expression of P-Akt and NFkappaB was detected by an
      immunohistochemical SP technique with HPV DNA detetion by PCR in 26 cases of
      cervical carcinoma tissues, 18 cases of cervical intraepithelial neoplasia
      tissues (CINI / n = 5, CINII / n = 3, CINIII / n = 10) and 19 cases of chronic
      cervicitis tissues. The different expressions of P-Akt and NFkappaB were compared
      in different pathological types of cervical carcinoma (cervical squamous cell
      carcinoma, cervical adenocarcinoma), different pathological grading (high,
      medium, poorly differentiated) and different clinical stage (FIGO I to IV). The
      relationships between P-Akt and NFkappaB, respectively, with HPV infection in
      cervical carcinoma were analyzed. RESULTS: The positive expression rate of P-Akt
      in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 21.05%,
      66.67%, and 92.31%, respectively. There was no obvious difference in the
      expression of P-Akt in cervical carcinoma in different pathological types or in
      pathological grading and no obvious difference in different clinical stages. The
      positive expression rate of NFkappaB in chronic cervicitis tissues, CIN and
      cervical carcinoma tissues was 10.52%, 72.22% and 96.15%, respectively; there was
      no statistically significant difference among the groups for different
      pathological types and there was no obvious difference in different pathological
      grading or different clinical stage. There was an obviously positive correlation
      between P-Akt and NFkappaB expression rate and degree of disease (r = 0.998, p <
      0.05). Cervical carcinoma and CIN cases totaled 44; the positive expression rate
      of P-Akt was 87.55% in 32 cases of positive HPV-DNA of the 44 cases, and the
      positive expression rate of P-Akt was only 16.70% in 12 cases of negative HPV-DNA
      of the 44 cases. The positive expression rate of NFkappaB was obviously higher in
      the HPV DNA positive than in the HPV-DNA negative cases. There was a
      statistically significant difference among the groups (p < 0.05). CONCLUSION: The
      positive expression rate of P-Akt and NFkappaB was closely related with cervical
      disease extent, and closely related with HPV infection in cervical carcinoma.
      This study suggests that P-Akt and NFkappaB more probably play an important role
      in the occurrence of cervical carcinoma.

PMID- 22873099
TI  - Preoperative serum leptin levels in patients with endometrial cancer and its
      correlation with prognostic variables.
AB  - PURPOSE OF INVESTIGATION: Since leptin is believed to be a key player in
      carcinogenesis, a study has been designed to investigate the relationship between
      leptin levels and endometrial cancer. METHODS: A study including 30 patients with
      endometrial cancer and 30 healthy controls was carried out between November 2008
      and July 2009 in Hacettepe University Hospital. All patients with endometrial
      cancer underwent a complete surgical staging procedure including lymphadenectomy.
      Preoperative leptin levels of endometrial cancer patients and healthy controls
      were compared. The relationships between leptin levels and stage, grade,
      histological type and lymph node status of endometrial cancer cases were
      evaluated. RESULTS: The mean serum leptin levels were 16.9 ng/ml among
      endometrial cancer cases and 19.0 ng/ml among controls (p = 0.32). Of endometrial
      cancer cases, the mean leptin level was found to be 15.8 ng/ml for Stage I and
      18.5 ng/ml for Stage II-IV disease (p = 0.34). The figure was 17.7 ng/ml for
      endometrioid and 13.2 ng/ml for non-endometrioid type of tumor (p = 0.24). The
      mean leptin levels of 16.3 ng/ml for grade 1 and 19.9 ng/ml for grade 2-3 tumors
      were observed (p = 0.07). The cases with positive and negative lymph nodes had
      leptin levels of 20.2 ng/ml and 16.1 ng/ml, respectively (p = 0.30). CONCLUSIONS:
      Serum leptin levels in endometrial cancer patients were similar to healthy
      controls. Leptin did not show any significant correlation with stage, grade,
      histological type and node metastases in endometrial cancer.

PMID- 22873100
TI  - Expression of tumor associated antigens CA 15-3 and CA 19-9 in trophoblast of the
      normal human placenta.
AB  - Mucin 1 (MUC1) is abundantly expressed by various organs, including human
      placenta and endometrium. Since glycan modifications of MUC1 are potentially
      relevant for physiological as well as pathological processes, this study was
      aimed at establishing an expression profile of two MUC1 glycoepitopes, CA 15-3
      and CA 19-9, in trophoblast throughout pregnancy. Immunohistochemical analysis of
      normal placenta demonstrated that trophoblast cells express both mucin antigens
      throughout gestation with a distinct staining pattern. The staining of villous
      trophoblast was non-uniform for both antigens, and stronger for CA 15-3. Only a
      proportion of extravillous trophoblast of the cell column, in decidual stroma or
      lining blood vessels was also stained. Whether the studied MUC 1 glycoforms can
      be linked to trophoblast cells invasion remains to be established.

PMID- 22873101
TI  - Regulation of radiosensitivity by HDAC inhibitor trichostatin A in the human
      cervical carcinoma cell line Hela.
AB  - Histone deacetylase (HDAC) inhibitors play an important role in inducing growth
      arrest, differentiation, and/or apoptosis in cancer cells. Given their ability to
      disrupt critical biological processes in cancer cells, these agents are emerging
      as potential therapeutics for cancer. Recently, it has been identified that HDAC
      inhibitors can also efficiently enhance the radiation sensitivity of cells, both
      in vitro and in vivo. In this study, we investigated whether the potent HDAC
      inhibitor, Trichostatin A, modulates the radiation sensitivity of the human
      cervical carcinoma cell line Hela under hypoxic conditions. We concluded that TSA
      could significantly inhibit the proliferation of Hela cells in a dose-and time
      dependent manner under normoxic and hypoxic conditions. Hypoxia resulted in the
      cervical carcinoma Hela cells resistant to TSA. The findings from clonogenic
      survival assays indicate that incubation with TSA for 24 hours prior to
      irradiation enhances the radiation sensitivity of Hela cells under hypoxic
      conditions. More generally, we found Hela cells under hypoxic conditions treated
      with TSA could significantly down-regulate the expressions of HIF-1alpha and VEGF
      proteins. Taken together, our results demonstrated that TSA acts as a powerful
      radiosensitizer in Hela cells under hypoxic conditions probably by down-regulated
      expression of HIF-1alpha and VEGF proteins.

PMID- 22873102
TI  - Toll-like receptor 4 signaling promotes the immunosuppressive cytokine production
      of human cervical cancer.
AB  - OBJECTIVES: To investigate the expression of TLR-4 (toll-like receptor) on human
      cervical cancer and find the biological function of the TLR-4 signal system.
      METHODS: The immunohistochemistry method was performed to study the protein
      expression and distribution of TLR-4. The viability of HeLa cells was determined
      by cell viability assay. Cell proliferation was detected by FCM, ELISA and
      Western blot were used to observe the gene and protein expression of IL-6 and TGF
      beta1 in Hela cell lines. RESULTS: TLR-4 was over-expressed in cervix cancer, and
      its activation by LPS promotes proliferation and anti-apoptosis in Hela cells in
      vitro. Moreover the cell line proliferation increased in a dose- and time
      dependent manner. The production of IL-6 and TGF-beta1 were promoted through the
      activation of the NF-kappaB signaling pathway.

PMID- 22873103
TI  - Evaluation of endometrium by transvaginal ultrasonography and Doppler in
      tamoxifen-treated women with breast cancer.
AB  - PURPOSE: The purpose of this study was to investigate the discriminative role of
      transvaginal ultrasonography and Doppler measurements on the detection of
      endometrial pathologies in tamoxifen-treated breast cancer patients. METHODS:
      Tamoxifen-treated breast cancer patients were included in this prospective study
      between February 2009 and June 2010. The subjects were assessed by gynecologic
      examination and transvaginal gray-scale and Doppler sonography. The patients
      whose endometrial thicknesses were more than 6 mm underwent
      endocervical/endometrial curettage for histopathological examination. RESULTS:
      There were 98 tamoxifen-treated patients with breast cancer enrolled in the
      study, providing 141 ultrasound evaluations. Uterine artery pulsatility index was
      significantly lower in postmenopausal than premenopausal patients (p: 0.013).
      Endocervical and endometrial curettage was performed in 52 patients. It was more
      prevalent that the endometrial strip was > or = 6 mm in women with abnormal
      endometrial histopathology (p: 0.020). However the women with abnormal
      endometrial histopathology presented lower vascular indices; the only significant
      difference was in myometrial pulsatility index (p: 0.036). CONCLUSION: The most
      evident tool for evaluating the endometrium in tamoxifen-treated breast cancer
      patients is still the transvaginal measurement of its thickness. It exists that
      Doppler ultrasonographic assessment of uterine, radial and spiral vasculature has
      no additional benefit for detection of endometrial pathology.

PMID- 22873104
TI  - Status quo and prevention of overtreatment in cervical diseases.
AB  - The objective of this paper was to review the diagnosis and treatment of cervical
      diseases. Often, due to improper judgment of interventional indications for
      cervical lesions, overtreatment to various degrees takes place, influencing
      patients' health and lives. This review analyzes the expression, causes and
      negative aspects of overtreatment of cervical lesions, and discusses the
      available therapeutic methods for cervical lesions, to remind gynecologists to
      master the interventional indications for proper treatment and avoid
      overtreatment, so as to achieve normalization and individualization in treating
      gynecologic diseases.

PMID- 22873105
TI  - Sentinel lymph node detection by intranipple injection of patent blue dye in
      breast cancer: a preliminary report of a feasibility study.
AB  - Sentinel lymph node (SLN) biopsy is a well established option for assessing
      axillary lymph node status in breast cancer. Several techniques have been applied
      so far (superficial or deeper ones). Based on anatomical features of the
      lymphatic drainage in the breast, we assessed the feasibility of an intranipple
      approach for SLN mapping. Our data support the feasibility of SLN detection by
      our technique, with a high rate of SLN identification, which could be used in
      clinical practice as an alternative to the peri-areolar approach.

PMID- 22873106
TI  - Leiomyosarcoma of the vulva.
AB  - Malignant tumors of the vulva soft tissue are uncommon. About 1-3% are sarcomas.
      They can be mistaken as benign lesions, leading to misdiagnosis and mistreatment.
      A case of a 71-year-old woman with a leiomyosarcoma of the vulva is presented.
      The surgical excision of the lesion is described and there were no additional
      malignancies or lesions found. There was no need for adjuvant therapy.

PMID- 22873107
TI  - Bilateral juvenile fibroadenosis of the breast: management with subcutaneous
      mastectomy and silicone implant placement.
AB  - Bilateral fibroadenosis is a rare, benign disorder, affecting adolescents or
      women of childbearing age. Choosing the most optimal therapy that manages both
      the physical and psychological aspects of the disease is a challenge. The goals
      of the treatment are complete resection of the lesions with optimal cosmesis.
      Options range from cryoablation, ultrasound-guided vacuum-assisted eradication
      and simple excision of the lesions to subcutaneous mastectomy with
      reconstruction. We present a case of a 25-year-old woman with 37 complex
      fibroadenomas affecting both breasts who was treated with nipple-sparing
      subcutaneous mastectomy and silicone implant reconstruction to both the surgeons'
      and patient's satisfaction.

PMID- 22873108
TI  - Primary ovarian small cell carcinoma of pulmonary type with enlarged paraaortic
      lymph node masses: a case report and review of the literature.
AB  - INTRODUCTION: Small cell carcinoma of the ovary of pulmonary type, is a rare,
      aggressive tumour with poor prognosis and its optimal management is unclear. CASE
      PRESENTATION: A 55-year-old Caucasian woman presented with abdominal discomfort
      and left lumbar pain within a three-week period. At exploratory laparotomy, a 8
      cm solid cystic mass of the left ovary was found infiltrating the sigmoid colon,
      and a bulky mass (11 x 7 x 4 cm) in the left paraaortic infrarenal region.
      Histopathological features resembling small cell carcinoma of the lungs and
      positive immunohistochemical stains provided a definite diagnosis of IIIC ovarian
      small cell carcinoma of pulmonary type. After six cycles chemotherapy with
      carboplatin and etoposide, the patient is still alive at 21 months from initial
      diagnosis. DISCUSSION: In this case, the absence of peritoneal involvement and
      the extensive paraaortic adenopathy is suggestive of a different pattern of
      spread of this rare tumour. Optimal treatment seems to be radical primary
      debulking surgery resulting in no residual disease, maximizing the effect of
      adjuvant chemotherapy for this biological aggressive tumour.

PMID- 22873109
TI  - G-CSF induces focal intense bone marrow FDG uptake mimicking multiple bone
      metastases from uterine cervical cancer: a case report and review of the
      literature.
AB  - We describe a case of FIGO Stage IB2 uterine cervical cancer which showed focal
      intense bone marrow FDG uptake mimicking bone metastases after the administration
      of G-CSF This case highlights the importance of avoiding the administration of G
      CSF prior to PET imaging.

PMID- 22873110
TI  - A huge retroperitoneal liposarcoma: case report.
AB  - BACKGROUND: Soft tissue sarcomas are rare and account for less than 1% of all
      newly diagnosed malignancies. One-third of malignant tumors arising in the
      retroperitoneum are sarcomas. Liposarcoma is the most common soft tissue sarcoma
      and retroperitoneal sarcoma. Liposarcoma accounts for at least 20% of all
      sarcomas in adults and up to 41% of all retroperitoneal sarcomas. Here we present
      the case of a huge retroperitoneal liposarcoma and a brief literature review.
      CASE REPORT: A 34-year-old woman was referred to our hospital from a local
      clinic, because of abdominal distention, pain, and palpable mass. On admission we
      found that her abdomen was markedly distended. Computed tomography showed a the
      huge left ovarian mass that occupied almost the entire abdominal cavity. The mass
      consisted mainly of fat, and calcified material. She was operated under the
      diagnosis of a huge teratoma. The tumor was located in the retroperitoneal cavity
      and it abutted the left adnexa. The retroperitoneal tumor, including the left
      adnexa was removed. The tumor measured 22 x 15 x 11 cm, and showed many
      histological and pathological findings. On the basis of the histopathological
      finding, the tumor was diagnosed as a dedifferentiated liposarcoma of the
      retroperitoneum. The patient is presently undergoing radiation therapy.
      CONCLUSION: In retroperitoneal liposarcoma, histological subtype, incomplete
      resection, contiguous organ resection, and older age are strongly associated with
      tumor-related mortality. For liposarcoma, it is necessary to customize the
      treatment strategy on a case-by-case basis.

PMID- 22873111
TI  - Long-term disease-free survival in three ovarian cancer patients with a single
      relapse.
AB  - Recurrent ovarian cancer with long-term survival is uncommon and often associated
      with poor prognosis. We report three cases of patients with advanced ovarian
      cancer who have achieved long-term disease-free survival following a single prior
      relapse. Case 1 relapsed with a localized bulky tumor and received a complete
      surgical resection and chemotherapy. Case 2 had a persistent central pelvic tumor
      after debulking surgery and second-line chemotherapy, and yet achieved excellent
      control with concurrent chemoradiation to the true pelvis. Case 3 relapsed with
      paraaortic lymph node metastasis and probable lung metastasis (subsequently
      negated by positron emission tomography) and received chemotherapy alone. These
      three patients have since remained disease-free for 13, 12, and seven years,
      respectively, since their first relapse. We conclude that select patients can
      obtain long-term disease-free survival after the first relapse by accurate
      restaging and aggressive multimodality treatment.

PMID- 22873112
TI  - Endometrioid ovarian cancer arising from an endometriotic cyst in a young
      patient.
AB  - OBJECTIVE: To present a case of a young woman with ovarian endometrioid
      adenocarcinoma arising from an endometriotic cyst and review of the literature.
      CASE REPORT: A 33-year-old woman, gravid 2, para 2 was admitted to our department
      with a 5 cm adnexal mass. Diagnostic laparoscopy was performed and pathological
      examination demonstrated an endometriotic cyst with an area of an ovarian
      endometrioid adenocarcinoma well differentiated, with no capsular invasion. One
      month after the operation the patient underwent MRI which revealed a 6 cm mass in
      the Douglas pouch. The multidisciplinary oncology council decided on exploratory
      laparotomy, which revealed no pathology. After that the multidisciplinary
      oncology council decided on adjuvant chemotherapy and the patient received four
      cycles of carboplatin/taxol. CONCLUSION: It should always be considered that even
      when there are no risk factors for malignancy occurrence, a high index of
      suspicion is necessary and will help to prevent delay in the diagnosis of this
      rare neoplasm.

PMID- 22873113
TI  - Removal of a vaginal leiomyoma presenting as tumor previa allowing vaginal birth.
AB  - Leiomyomas of the vagina are very rare tumors of the female genital tract with
      only 300 cases reported so far. A case of removal of the vaginal leiomyoma
      presenting as tumor previa in advanced pregnancy is described. Removal of the
      tumor allowed vaginal birth three weeks after surgery.

PMID- 22873114
TI  - Endometrial stromal sarcoma in a 29-year-old patient. Case report and review of
      the literature.
AB  - OBJECTIVE: Endometrial stromal sarcomas are rare tumors accounting for about 0.2%
      of all genital tract malignancies. They are considered to occur more often in
      premenopausal women. Endometrial stromal sarcomas are hormone sensitive tumors. A
      state of hyper-estrogenemia could act as a growth stimulus. Given the rarity of
      these tumors there are limited reports in the literature referring to the
      clinical management and final outcome of these cases. CASE: The patient, a 29
      year-old woman, had a surgical history of myomectomy in another hospital three
      months before her referal to our department. The histological examination of the
      removed myoma showed an endometrial stromal sarcoma. Total abdominal
      hysterectomy, with bilateral salpingo-oophorectomy, omentectomy and elective
      pelvic lymphadenectomy were then performed as a second radical surgical approach.
      CONCLUSION: Endometrial stromal sarcomas are uncommon and their differential
      diagnosis from typical submucosal uterine myomas or benign endometrial polyps
      could be difficult. The hysteroscopic features of uterine sarcomas are often
      similar to those of endometrial polyps or submucosal myomas. The histological
      examination of the specimen is necessary to exclude malignancy and establish the
      final diagnosis. Total abdominal hysterectomy, bilateral salpingo-oopherectomy
      with pelvic lymphadenectomy is the optimal treatment in cases of endometrial
      stromal sarcomas.

PMID- 22873115
TI  - Primary ovarian leiomyosarcoma.
AB  - BACKGROUND: Primary ovarian leiomyosarcoma is an extremely rare subtype of
      ovarian sarcomas. It most commonly occurs in postmenopausal women and has
      unfavorable prognosis. CASE: The patient, a 58-year-old postmenopausal woman,
      presented with a complaint of abdominal pain. Preoperative examination revealed
      an intraabdominal mass 25 x 17 x 14 cm in the right adnexa. She underwent
      bilateral salpingo-oophorectomy, total omentectomy, appendectomy and bilateral
      pelvic lymphadenectomy. The histopathology revealed leiomyosarcoma of the right
      ovary Stage Ia. She did not receive any postoperative adjuvant therapy. Follow-up
      21 months after initial surgery, showed no evidence of recurrence. CONCLUSION:
      Additional studies are needed to understand more about the nature, clinical
      behavior and treatment of this very rare tumor.

PMID- 22873116
TI  - Primary retroperitoneal mucinous cystadenoma adjacent to the kidney: report of
      two cases and review.
AB  - We report two cases of primary retroperitoneal mucinous cystadenomas mistaken as
      renal cysts and discuss the differential diagnosis and management of this tumor.

PMID- 22873117
TI  - Inhibition of nitric oxide synthase attenuates cutaneous vasodilation during warm
      moxibustion-like thermal stimulation in humans.
AB  - OBJECTIVES: This study investigated if nitric oxide (NO) and/or prostaglandin
      (PG) are responsible for cutaneous vasodilation during warm moxibustion-like
      thermal stimulation (WMTS). DESIGN: For two protocols, two microdialysis
      membranes were placed in the medial forearm skin. In the first protocol (n=8),
      the sites were randomly assigned and perfused with N(G)-nitro-l-arginine methyl
      ester hydrochloride (l-NAME), an NO synthase inhibitor or Ringer's solution
      (control site). Similarly, two microdialysis membranes were placed in the medial
      forearm skin in the second protocol (n=6). One site was perfused with ketorolac
      (Keto), the cyclo-oxygenase (COX) pathway inhibitor, and the other site was
      perfused with Ringer's solution (control site). In both protocols, cutaneous
      vasodilation was induced using WMTS with an electronic warm moxibustion treatment
      appliance. After 10 minutes of baseline recording, WMTS was applied to the
      forearm skin for 20 minutes and recovery was monitored over a period of 20
      minutes. Skin blood flow (SkBF) at each site was measured using laser-Doppler
      flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler
      flux/mean arterial blood pressure (BP). SETTINGS/LOCATION: The study was
      conducted in a laboratory at the Kansai University of Health Sciences. SUBJECTS:
      The subjects were 14 healthy male volunteers. INTERVENTIONS: WMTS was applied to
      the medial forearm skin using an electronic warm moxibustion treatment appliance.
      OUTCOME MEASURES: SkBF, skin temperature (Tsk), core body temperature (Tc), heart
      rate (HR), and BP were outcome measures. RESULTS: In the first protocol, peak CVC
      values during WMTS at the site perfused with l-NAME were significantly decreased,
      compared to those at the control site (p<0.05). In the second protocol, peak CVC
      values during WMTS did not differ between the control site and the Keto site
      (p>0.05). CONCLUSIONS: These data demonstrate that NO is involved in the
      mechanism of cutaneous vasodilation induced by WMTS. Furthermore, increases in
      CVC despite inhibition of the COX pathway suggest that PG does not contribute to
      cutaneous vasodilation during WMTS.

PMID- 22873118
TI  - Second-generation covalent TMP-tag for live cell imaging.
AB  - Chemical tags are now viable alternatives to fluorescent proteins for labeling
      proteins in living cells with organic fluorophores that have improved brightness
      and other specialized properties. Recently, we successfully rendered our TMP-tag
      covalent with a proximity-induced reaction between the protein tag and the ligand
      fluorophore label. This initial design, however, suffered from slow in vitro
      labeling kinetics and limited live cell protein labeling. Thus, here we report a
      second-generation covalent TMP-tag that has a fast labeling half-life and can
      readily label a variety of intracellular proteins in living cells. Specifically,
      we designed an acrylamide-trimethoprim-fluorophore (A-TMP-fluorophore v2.0)
      electrophile with an optimized linker for fast reaction with a cysteine (Cys)
      nucleophile engineered just outside the TMP-binding pocket of Escherichia coli
      dihydrofolate reductase (eDHFR) and developed an efficient chemical synthesis for
      routine production of a variety of A-TMP-probe v2.0 labels. We then screened a
      panel of eDHFR:Cys variants and identified eDHFR:L28C as having an 8-min half
      life for reaction with A-TMP-biotin v2.0 in vitro. Finally, we demonstrated live
      cell imaging of various cellular protein targets with A-TMP-fluorescein, A-TMP
      Dapoxyl, and A-TMP-Atto655. With its robustness, this second-generation covalent
      TMP-tag adds to the limited number of chemical tags that can be used to
      covalently label intracellular proteins efficiently in living cells. Moreover,
      the success of this second-generation design further validates proximity-induced
      reactivity and organic chemistry as tools not only for chemical tag engineering
      but also more broadly for synthetic biology.

PMID- 22873120
TI  - It's in the genes! Human genetic diversity and the response to anthrax vaccines.

PMID- 22873121
TI  - Toxicity profiles of HER2/neu peptide anticancer vaccines: the picture from
      Phase/I and II clinical trials.

PMID- 22873119
TI  - Pathogen-driven gastrointestinal cancers: Time for a change in treatment
      paradigm?
AB  - The regulation of cancerous tumor development is converged upon by multiple
      pathways and factors. Besides environmental factors, gastrointestinal (GI) tract
      cancer can be caused by chronic inflammation, which is generally induced by
      bacteria, viruses, and parasites. The role of these inducers in cancer
      development, cell differentiation and transformation, cell cycle deregulation,
      and in the expression of tumor-associated genes cannot be ignored. Although
      Helicobacter pylori activates many oncogenic pathways, particularly those in
      gastric and colorectal cancers, the role of viruses in tumor development is also
      significant. Viruses possess significant oncogenic potential to interfere with
      normal cell cycle control and genome stability, stimulating the growth of
      deregulated cells. An increasing amount of recent data also implies the
      association of GI cancers with bacterial colonization and viruses. This review
      focuses on host-cell interactions that facilitate primary mechanisms of
      tumorigenesis and provides new insights into novel GI cancer treatments.

PMID- 22873123
TI  - Cervarix(r): a bivalent vaccine against HPV types 16 and 18, with cross
      protection against other high-risk HPV types.
AB  - Cervical cancer is the third most common cancer in women worldwide and often
      affects women under 40 years of age with young families. Vaccination against HPV
      is a major advancement, as it offers primary prevention against the infectious
      agent that is the main cause of the disease. The bivalent AS04-adjuvanted
      prophylactic HPV vaccine provides high efficacy against disease associated with
      HPV 16 and 18, as well as significant cross-protection against some HPV types not
      included in the vaccine. Protection against HPV 45 may be particularly important,
      as it is relatively more common in adenocarcinoma. The vaccine's antibody
      response profile suggests a long duration of immunity. Safety data have been
      reassuring, which is not unexpected, given that the vaccine is composed of virus
      like particles, rather than being a live-virus vaccine.

PMID- 22873124
TI  - The future of plague vaccines: hopes raised by a surrogate, live-attenuated
      recombinant vaccine candidate.
AB  - Yersinia pestis (YP) is the Gram-negative etiological agent of plague against
      which no commercial vaccine exists to prophylactically prevent a potential
      outbreak due to natural or bio-warfare/terrorism-mediated causes. The US FDA only
      recently approved levofloxacin to combat this deadly pathogen. In the article
      under review, an attenuated, recombinant Salmonella typhimurium DeltaphoPQ mutant
      strain producing YP antigens F1, LcrV and F1-V (fusion protein) from either low
      copy pBR or high-copy pUC vectors (maintained by plasmid addiction rather than
      antibiotic selection pressure) were evaluated for their ability to induce a
      humoral immune response in both mice and rabbits. This study highlights the need
      for developing a well-tolerated YP vaccine that, through the oral route, can be
      readily administered and elicit both mucosal and systemic anti-plague humoral
      immunity.

PMID- 22873126
TI  - Progress and hurdles in the development of vaccines against enterotoxigenic
      Escherichia coli in humans.
AB  - Diarrhea is the second leading cause of death in children younger than 5 years.
      Enterotoxigenic Escherichia coli (ETEC) strains are the most common bacterial
      cause of diarrhea in young children living in endemic countries and children and
      adults traveling to these areas. Pathogenesis of ETEC diarrhea has been well
      studied, and the key virulence factors are bacterial colonization factor antigens
      and enterotoxins produced by ETEC strains. Colonization factor antigens mediate
      bacteria attachment to host small intestinal epithelial cells and subsequent
      colonization, whereas enterotoxins including heat-labile and heat-stable toxins
      disrupt fluid homeostasis in host epithelial cells, which leads to fluid and
      electrolyte hypersecretion and diarrhea. Vaccines stimulating host anti-adhesin
      immunity to block ETEC attachment and colonization and also antitoxin immunity to
      neutralize enterotoxicity are considered optimal for prevention of ETEC diarrhea.
      Vaccines under development have been designed to stimulate local intestinal
      immunity and are either oral vaccines or transcutaneous vaccines. A cholera
      vaccine (Dukoral(r)) does stimulate anti-heat-labile toxin immunity and is
      licensed for short-term protection of ETEC diarrhea in travelers in some
      countries. Newer experimental ETEC vaccine candidates are being developed with
      hope to provide long-lasting and more broad-based protection against ETEC. Some
      have shown promising results in safety and immunogenicity studies and are
      approaching field trials for efficacy. A key problem is the development of a
      vaccine that is both practical and inexpensive so that it can be affordable for
      use in poor countries where it is needed.

PMID- 22873125
TI  - Preventing urinary tract infection: progress toward an effective Escherichia coli
      vaccine.
AB  - Uncomplicated urinary tract infections (UTIs) are common, with nearly half of all
      women experiencing at least one UTI in their lifetime. This high frequency of
      infection results in huge annual economic costs, decreased workforce productivity
      and high patient morbidity. At least 80% of these infections are caused by
      uropathogenic Escherichia coli (UPEC). UPEC can reside side by side with
      commensal strains in the gastrointestinal tract and gain access to the bladder
      via colonization of the urethra. Antibiotics represent the current standard
      treatment for UTI; however, even after treatment, patients frequently suffer from
      recurrent infection with the same or different strains. In addition, successful
      long-term treatment has been complicated by a rise in both the number of
      antibiotic-resistant strains and the prevalence of antibiotic-resistance
      mechanisms. As a result, preventative approaches to UTI, such as vaccination,
      have been sought. This review summarizes recent advances in UPEC vaccine
      development and outlines future directions for the field.

PMID- 22873127
TI  - Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and
      challenges.
AB  - The aim of this review is to make researchers aware of the benefits of an
      efficient quality control system for prediction of a developed vaccine's
      efficacy. Two major goals should be addressed when inactivating a virus for
      vaccine purposes: first, the infectious virus should be inactivated completely in
      order to be safe, and second, the viral epitopes important for the induction of
      protective immunity should be conserved after inactivation in order to have an
      antigen of high quality. Therefore, some problems associated with the virus
      inactivation process, such as virus aggregate formation, protein crosslinking,
      protein denaturation and degradation should be addressed before testing an
      inactivated vaccine in vivo.

PMID- 22873128
TI  - Cancer vaccines: should we be targeting patients with less aggressive disease?
AB  - There is enthusiasm for using vaccines to stimulate the immune system to treat
      cancer. In this article, the authors review the evolution of vaccines evaluated
      in clinical trials, starting with Phase III trials in metastatic disease and
      progressing to trials in the adjuvant setting. Data from these trials suggest
      that cancer vaccines may be more effective in patients with lower volume disease,
      and data from the E75 peptide vaccine trials suggest that vaccines may be most
      effective in less aggressive disease.

PMID- 22873129
TI  - Liposomes containing lipid A: an effective, safe, generic adjuvant system for
      synthetic vaccines.
AB  - Liposomes containing monophosphoryl lipid A (MPLA) have previously exhibited
      considerable potency and safety in human trials with a variety of candidate
      vaccines, including vaccines to malaria, HIV-1 and several different types of
      cancer. The long history of research and development of MPLA and liposomal MPLA
      as vaccine adjuvants reveals that there are numerous opportunities for creation
      and development of generic (nonproprietary) adjuvant system formulations with
      these materials that are not only highly potent and safe, but also readily
      available as native materials or as synthetic compounds. They are easily
      manufactured as potentially inexpensive and easy to use adjuvant systems and
      might be effective even with synthetic peptides as antigens.

PMID- 22873132
TI  - Actinide chemistry in ionic liquids.
AB  - This Forum Article provides an overview of the reported studies on the actinide
      chemistry in ionic liquids (ILs) with a particular focus on several fundamental
      chemical aspects: (i) complex formation, (ii) electrochemistry, and (iii)
      extraction behavior. The majority of investigations have been dedicated to
      uranium, especially for the 6+ oxidation state (UO2(2+)), because the chemistry
      of uranium in ordinary solvents has been well investigated and uranium is the
      most abundant element in the actual nuclear fuel cycles. Other actinides such as
      thorium, neptunium, plutonium, americium, and curiumm, although less studied, are
      also of importance in fully understanding the nuclear fuel engineering process
      and the safe geological disposal of radioactive wastes.

PMID- 22873131
TI  - Development of an osmotically-driven pellet coated with acrylic copolymers
      (Eudragit(r) RS 30 D) for the sustained release of oxymatrine, a freely water
      soluble drug used to treat stress ulcers (I): in vitro and in vivo evaluation in
      rabbits.
AB  - PURPOSE: To develop an osmotically-driven pellet coated with polymeric film for
      sustained release of oxymatrine (OMT), a freely water soluble drug. METHODS:
      Pellet containing OMT and sodium chloride (NaCl), an osmotically active agent,
      were prepared by extrusion/spheronization and then coated with acrylic copolymers
      (Eudragit((r)) RS 30 D) by the fluidized bed coating process. In vitro release
      and swelling behavior studies were employed to optimize and to evaluate the
      sustained-release behavior from the osmotically-driven pellets with film coated.
      Finally, in vivo evaluation in rabbits was employed to investigate the sustained
      plasma level of OMT and its active metabolite matrine. RESULTS: It was found that
      the F3 formulation, prepared with 20% NaCl and an 8% coating level, showed a
      continuous NaCl-induced water influx into the pellets providing a gradual
      sustained release of OMT for over 12 h. Finally, we confirmed that oral OMT with
      sustained release led to a gradual sustained plasma profile of both OMT, with a
      reduction in its bioavailability, and MT with an increase in the bioavailability
      compared with that of oral OMT with immediate release. CONCLUSIONS: The
      pharmaceutical parameters obtained suggested the potential usefulness of oral OMT
      with sustained release for the treatment of stress ulcers, as well as reducing
      the risk of MT-induced side effects.

PMID- 22873133
TI  - Allyloxy and propargyloxy group migration: role of remote group participation in
      the synthesis of 5-C-nucleosides and other sugar derivatives.
AB  - In 1-deoxy-xylofuranose derivatives possessing a good leaving group at 2-C,
      participation of allyloxy and propargyloxy substituents at 5-C results in loss of
      the 2-C substituent and attack of various nucleophiles at 5-C of the oxonium
      intermediate. Such participation of a benzyloxy or crotyloxy group leads to
      dioxabicyclo[2.2.1]heptane rings.

PMID- 22873172
TI  - Brief communication: assessment and validation of nonspermicidal condoms as
      specimen collection sheaths for semen analysis and assisted conception.
AB  - The choice of nonspermicidal sheaths for specimen collection for diagnosis and/or
      fertility treatment is limited. Those that are available tend to be relatively
      expensive and as a results, offered selectively to patients. This study describes
      the evaluation of three over-the-counter nonspermicidal condoms as alternatives
      to specialized specimen collection sheaths. Sheaths were incubated with motile
      sperm for up to 2 h and the percent Grade A motility, percent progressive
      motility and progressive velocity assessed using an 'in-house' computer-assisted
      semen analysis system every 30 min. Two of the sheaths tested, Pasante Naturelle
      (PN) and the Durex Avanti Ultima were shown to be highly toxic to sperm, leading
      to immobilization of most specimens within 1 h. However the loss of sperm
      motility when sperm were incubated with the Pasante Unique (PU) condom was no
      greater than with either the control (rigid 60 ml specimen container) or the Male
      Factor Pak (MFP), a commercially available specialized semen collection sheath.
      In conclusion, the PU brand of condom could be used as a cheaper alternative to
      the specimen collection sheaths currently available. Furthermore, some brands of
      condom sold as nonspermicidal are in fact toxic to sperm and will immobilize most
      specimens within 1 h.

PMID- 22873171
TI  - The key role of insulin-like growth factor I in limbal stem cell differentiation
      and the corneal wound-healing process.
AB  - Limbal stem cells (LSC), which reside in the basal layer of the limbus, are
      thought to be responsible for corneal epithelial healing after injury. When the
      cornea is damaged, LSC start to proliferate, differentiate, and migrate to the
      site of injury. To characterize the signaling molecules ensuring communication
      between the cornea and LSC, we established a mouse model of mechanical corneal
      damage. The central cornea or limbal tissue was excised at different time
      intervals after injury, and the expression of genes in the explants was
      determined. It was observed that a number of genes for growth and differentiation
      factors were significantly upregulated in the cornea rapidly after injury. The
      ability of these factors to regulate the differentiation and proliferation of
      limbal cells was tested. It was found that the insulin-like growth factor-I (IGF
      I), which is rapidly overexpressed after injury, enhances the expression of IGF
      receptor in limbal cells and induces the differentiation of LSC into cells
      expressing the corneal cell marker, cytokeratin K12, without any effect on limbal
      cell proliferation. In contrast, the epidermal growth factor (EGF) and fibroblast
      growth factor-beta (FGF-beta), which are also produced by the damaged corneal
      epithelium, supported limbal cell proliferation without any effect on their
      differentiation. Other factors did not affect limbal cell differentiation or
      proliferation. Thus, IGF-I was identified as the main factor stimulating the
      expression of IGF receptors in limbal cells and inducing the differentiation of
      LSC into cells expressing corneal epithelial cell markers. The proliferation of
      these cells was supported by EGF and FGF.

PMID- 22873173
TI  - Metabolomic investigation of the anti-platelet aggregation activity of
      ginsenoside Rk1 reveals attenuated 12-HETE production.
AB  - Comprehensive metabolomics analysis is an effective method of measuring
      metabolite levels in the body following administration of a pharmaceutical
      compound and can allow for monitoring of the effects of the compound or
      assessment of appropriate treatment options for individual patients. In the
      present metabolomics study, samples pretreated with antiplatelet compounds were
      extracted and subjected to ultraperformance liquid chromatography/quadrupole time
      of-flight mass spectrometry. The acquired data were processed using peak
      clustering and evaluated by partial least-squares (PLS) and orthogonal
      projections to latent structures discriminant analyses (OPLS-DA). As a result,
      meaningful endogenous metabolites, namely eicosanoids and thromboxane B(2)
      (TXB(2)), were identified. TXB(2), a key element in platelet aggregation, was
      decreased upon ginsenoside Rk(1) treatment via inhibition of cyclooxygenase (COX)
      activity. One of the arachidonic acid (AA) metabolites, 12-hydroxy-5,8,10,14
      eicosatetraenoic acid (12-HETE), was decreased significantly in the ginsenoside
      Rk(1)-treated platelets compared to the AA-induced group. In the mechanism study
      of ginsenoside Rk(1), a strong linkage to intracellular calcium levels, which
      induce platelet activation, was found. Additionally, the translocation of 12-LOX
      from cytosol to membrane, which is related with the intracellular calcium levels,
      was determined. Therefore, a decreased 12-HETE level induced by ginsenoside Rk(1)
      on antiplatelet aggregation is related to 12-LOX translocation resulting from
      decreased Ca(2+) levels. This study shows that global metabolomic analysis has
      potential for use in understanding the biological behavior of antiplatelet drugs.

PMID- 22873175
TI  - Spontaneous formation of vesicles by sodium 2-dodecylnicotinate in water.
AB  - The surface activity and aggregation behavior of a synthesized nicotinic acid
      based anionic surfactant, sodium 2-dodecylnicotinate, were studied in aqueous
      solution. The self-assembly formation was investigated by use of a number of
      techniques, including surface tension and conductivity measurements, fluorescence
      spectroscopy, dynamic light scattering measurement, gel permeation
      chromatography, and microscopy. The amphiphile exhibits two breaks in the surface
      tension vs concentration plot, indicating stepwise aggregate formation and thus
      producing two values of the aggregation concentration. Stepwise aggregation of
      the amphiphile was further confirmed by steady-state fluorescence spectroscopy
      using pyrene as a probe molecule, and also the micropolarity of the aggregates
      was determined. The rigidity of the microenvironment was estimated by determining
      steady-state fluorescence anisotropy using 1,6-diphenyl-1,3,5-hexatriene as a
      fluorescence probe molecule. The average hydrodynamic radius and size
      distribution of the aggregate suggest formation of larger aggregates in aqueous
      solution. The formation of vesicles in water was established by conductivity
      measurement and a dye entrapment experiment. The entrapment of a small solute and
      the release capability have also been examined to demonstrate these bilayers form
      enclosed vesicles. Transmission electron micrographs revealed the existence of
      closed vesicles and closed tubules in aqueous solution. Therefore, for the first
      time, it has been observed that this simple single-chain nicotinic acid based
      amphiphile spontaneously assembles to vesicles in aqueous solution.

PMID- 22873174
TI  - A combination of intradermal jet-injection and electroporation overcomes in vivo
      dose restriction of DNA vaccines.
AB  - BACKGROUND: The use of optimized delivery devices has been shown to enhance the
      potency of DNA vaccines. However, further optimization of DNA vaccine delivery is
      needed for this vaccine modality to ultimately be efficacious in humans. METHODS:
      Herein we evaluated antigen expression and immunogenicity after intradermal
      delivery of different doses of DNA vaccines by needle or by the Biojector jet
      injection device, with or without the addition of electroporation (EP). RESULTS:
      Neither needle injection augmented by EP nor Biojector alone could induce higher
      magnitudes of immune responses after immunizations with a high dose of DNA. After
      division of a defined DNA dose into multiple skin sites, the humoral response was
      particularly enhanced by Biojector while cellular responses were particularly
      enhanced by EP. Furthermore, a close correlation between in vivo antigen
      expression and cell-mediated as well as humoral immune responses was observed.
      CONCLUSIONS: These results show that two optimized DNA vaccine delivery devices
      can act together to overcome dose restrictions of plasmid DNA vaccines.

PMID- 22873176
TI  - Workplace violence in a large correctional health service in New South Wales,
      Australia: a retrospective review of incident management records.
AB  - BACKGROUND: Little is known about workplace violence among correctional health
      professionals. This study aimed to describe the patterns, severity and outcomes
      of incidents of workplace violence among employees of a large correctional health
      service, and to explore the help-seeking behaviours of staff following an
      incident. METHODS: The study setting was Justice Health, a statutory health
      corporation established to provide health care to people who come into contact
      with the criminal justice system in New South Wales, Australia. We reviewed
      incident management records describing workplace violence among Justice Health
      staff. The three-year study period was 1/7/2007-30/6/2010. RESULTS: During the
      period under review, 208 incidents of workplace violence were recorded. Verbal
      abuse (71%) was more common than physical abuse (29%). The most (44%) incidents
      of workplace violence (including both verbal and physical abuse) occurred in
      adult male prisons, although the most (50%) incidents of physical abuse occurred
      in a forensic hospital. Most (90%) of the victims were nurses and two-thirds were
      females. Younger employees and males were most likely to be a victim of physical
      abuse. Preparing or dispensing medication and attempting to calm and/or restrain
      an aggressive patient were identified as 'high risk' work duties for verbal abuse
      and physical abuse, respectively. Most (93%) of the incidents of workplace
      violence were initiated by a prisoner/patient. Almost all of the incidents
      received either a medium (46%) or low (52%) Severity Assessment Code. Few victims
      of workplace violence incurred a serious physical injury - there were no
      workplace deaths during the study period. However, mental stress was common,
      especially among the victims of verbal abuse (85%). Few (6%) victims of verbal
      abuse sought help from a health professional. CONCLUSIONS: Among employees of a
      large correctional health service, verbal abuse in the workplace was
      substantially more common than physical abuse. The most incidents of workplace
      violence occurred in adult male prisons. Review of the types of adverse health
      outcomes experienced by the victims of workplace violence and the assessments of
      severity assigned to violent incidents suggests that, compared with health care
      settings in the community, correctional settings are fairly safe places in which
      to practice.

PMID- 22873177
TI  - "Neurologist's contribution to the diagnosis of sine materia respiratory
      insufficiency: case report".
AB  - BACKGROUND: Right-to-left shunt (RLS) may be the cause of marked hypoxemia, a
      respiratory insufficiency which is usually difficult to diagnose by respiratory
      physicians as it develops in the absence of an intrinsic lung disease. CASE
      PRESENTATION: We report a case of RLS in a patient with a hepatopulmonary
      syndrome caused by chronic autoimmune cholangitis. RLS was suspected clinically
      by physical examination and by standard CT imaging and MIP reconstruction of the
      pulmonary vascular bed. Repeated previous transthoracic echocardiography (TTE)
      studies did not reveal shunts or any cardiac defect. The final diagnosis was made
      by means of a minimally invasive transcranial Doppler examination with the use of
      saline agitated with 0.5 ml of patient's blood as contrast solution. CONCLUSIONS:
      Transcranial Colour-Coded Duplex Sonography (TCCS) with saline contrast medium
      injection is described to have a higher sensitivity than TTE and comparable to
      transesophageal echocardiography (TEE) in RLS diagnosis. The collaboration of
      neurologists in diagnosing respiratory insufficiency is very important as the
      examination is simple, well tolerated in comparison with the discomfort
      associated with transesophageal echocardiography, and minimally invasive in
      comparison with angiography, which is the last diagnostic procedure in this
      clinical scenario. In order to confirm RLS, TCCS with blood-saline contrast
      medium injection should be performed for the diagnosis of chronic hypoxemia for
      which causes are not detected with routine clinical examinations.

PMID- 22873178
TI  - The Rabs: a family at the root of metazoan evolution.
AB  - Eukaryotic cells are distinguished by their compartmentalization into membrane
      enclosed organelles that exchange membranes and content in a highly ordered
      manner. Central in defining membrane identity are the Rabs, a large family of
      small GTPases that localize to distinct membranes and recruit specific regulators
      of membrane traffic. Two recent papers, including one by Klopper et al. in BMC
      Biology, present phylogenomic evidence that the Rab repertoire was established
      very early in eukaryotic evolution, and correlates with interspecies variations
      in organelles.

PMID- 22873179
TI  - Euthyroid status after total thyroidectomy due to functioning lung metastases
      from a clear cell variant of papillary thyroid carcinoma.
AB  - BACKGROUND: Although functioning thyroid cancer metastases have been reported,
      they have almost never been reported for the clear cell variant of papillary
      thyroid carcinoma (PTC). Here we describe a patient with disseminated lung
      metastases of the clear cell variant of PTC who presented in the euthyroid state
      despite discontinuance of levothyroxine after total thyroidectomy. PATIENT
      FINDINGS: A 49-year-old woman underwent total thyroidectomy for the clear cell
      variant of PTC in March 2002. Levothyroxine replacement was initiated after total
      thyroidectomy, but the patient was lost to follow-up 5 years after the operation.
      She did not take any levothyroxine for 4 years. Upon presentation to our
      institution, her initial thyroid function tests were a serum thyroid-stimulating
      hormone (TSH) of 4.51 mIU/L (0.30-5.00), total triiodothyronine of 82 ng/dL (60
      181), and free thyroxine of 1.21 ng/dL (0.89-1.76). The results of workups,
      including thyroid ultrasonography, chest computed tomography (CT) scan, and
      fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT,
      revealed that she had multiple metastases in the cervical lymph nodes and both
      lungs. She received 0.9 mg of recombinant human TSH (rhTSH) for 2 consecutive
      days followed by administration of 200 mCi 131I. A therapeutic whole body scan
      after 131I administration demonstrated intense uptake in the whole lung fields,
      suggesting functioning lung metastases. SUMMARY: It is extremely rare for
      metastatic PTC, even though it is a well-differentiated thyroid carcinoma, to
      produce a sufficient amount of thyroid hormones to result in euthyroid state
      after total thyroidectomy. To our knowledge, this is the first report of
      functioning lung metastases of the clear cell variant of PTC after total
      thyroidectomy that produced enough thyroid hormone to restore a euthyroid state.
      CONCLUSION: Functioning metastases from recurred PTC, particularly of the clear
      cell variant, are very rare. When they occur, rhTSH is required to prepare these
      patients for treatment with ablative doses of radioactive iodine (131I).

PMID- 22873181
TI  - Lisa Mojer-Torres, ESQ (December 1, 1956-April 7, 2011).

PMID- 22873180
TI  - Fermented fish oil suppresses T helper 1/2 cell response in a mouse model of
      atopic dermatitis via generation of CD4+CD25+Foxp3+ T cells.
AB  - BACKGROUND: Allergic skin inflammation such as atopic dermatitis (AD), which is
      characterized by pruritus and inflammation, is regulated partly through the
      activity of regulatory T cells (Tregs). Tregs play key roles in the immune
      response by preventing or suppressing the differentiation, proliferation and
      function of various immune cells, including CD4+ T cells. Recent studies report
      that fermentation has a tremendous capacity to transform chemical structures or
      create new substances, and the omega-3 polyunsaturated fatty acids (n-3 PUFAs) in
      fish oil can reduce inflammation in allergic patients. The beneficial effects of
      natural fish oil (NFO) have been described in many diseases, but the mechanism by
      which fermented fish oil (FFO) modulates the immune system and the allergic
      response is poorly understood. In this study, we produced FFO and tested its
      ability to suppress the allergic inflammatory response and to activate
      CD4+CD25+Foxp3+ Tregs. RESULTS: The ability of FFO and NFO to modulate the immune
      system was investigated using a mouse model of AD. Administration of FFO or NFO
      in the drinking water alleviated the allergic inflammation in the skin, and FFO
      was more effective than NFO. FFO treatment did increase the expression of the
      immune-suppressive cytokines TGF-beta and IL-10. In addition, ingestion of FFO
      increased Foxp3 expression and the number of CD4+CD25+Foxp3+ Tregs compared with
      NFO. CONCLUSIONS: These results suggest that the anti-allergic effect of FFO is
      associated with enrichment of CD4+CD25+ Foxp3+ T cells at the inflamed sites and
      that FFO may be effective in treating the allergic symptoms of AD.

PMID- 22873182
TI  - Medication-assisted recovery from opioid addiction: historical and contemporary
      perspectives.
AB  - Recovery is being used as a conceptual fulcrum for the redesign of addiction
      treatment and related support services in the United States. Efforts by policy,
      research, and clinical leaders to define recovery and calls for assertive models
      of long-term recovery management raise critical questions about how
      transformation efforts of recovery-focused systems will affect the
      pharmacotherapeutic treatment of opioid addiction and the status of patients
      participating in such treatment. This article highlights recent work advocating a
      recovery-oriented approach to medication-assisted treatment.

PMID- 22873184
TI  - Reducing stigma through education to enhance Medication-Assisted Recovery.
AB  - The National Alliance for Medication Assisted Recovery has started projects to
      address the stigma that impacts medication-assisted treatment. The Certified
      Medication Assisted Treatment Advocate Program trains patients and professionals
      for advocacy in seminars and conferences. The MARS Project educates (Einstein,
      Bronx, New York) buprenorphine and methadone patients to dispel stigma and
      achieve better treatment outcomes. Beyond MARS trains patients nationwide to
      replicate the MARS Project. Stop Stigma Now will create a national public
      relations campaign to overcome ignorance and stigma. These projects have the
      potential to end stigma and elevate medication-assisted treatment to its rightful
      place as the gold standard of treatment.

PMID- 22873185
TI  - Culturally competent substance abuse treatment with transgender persons.
AB  - Transgender individuals are misunderstood and inadequately treated in many
      conventional substance abuse treatment programs. This article reviews current
      concepts regarding the definition and diversity of transgenderism and summarizes
      the existing literature on the prevalence and correlates of substance use in
      transgendered populations. Examples of culturally competent and gender-sensitive
      treatment in specialized settings are cited, with a call to extend these
      initiatives throughout the gamut of service venues that engage transgender
      individuals. Cultural competence combined with gender sensitivity should improve
      the effectiveness of substance abuse treatment for transgender individuals and
      will contribute to the goal of providing effective services in an increasingly
      diverse society.

PMID- 22873183
TI  - Maintenance medication for opiate addiction: the foundation of recovery.
AB  - Illicit use of opiates is the fastest growing substance use problem in the United
      States, and the main reason for seeking addiction treatment services for illicit
      drug use throughout the world. It is associated with significant morbidity and
      mortality related to human immunodeficiency virus, hepatitis C, and overdose.
      Treatment for opiate addiction requires long-term management. Behavioral
      interventions alone have extremely poor outcomes, with more than 80% of patients
      returning to drug use. Similarly poor results are seen with medication-assisted
      detoxification. This article provides a topical review of the three medications
      approved by the Food and Drug Administration for long-term treatment of opiate
      dependence: the opioid-agonist methadone, the partial opioid-agonist
      buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action
      and treatment outcomes are described for each medication. Results indicate that
      maintenance medication provides the best opportunity for patients to achieve
      recovery from opiate addiction. Extensive literature and systematic reviews show
      that maintenance treatment with either methadone or buprenorphine is associated
      with retention in treatment, reduction in illicit opiate use, decreased craving,
      and improved social function. Oral naltrexone is ineffective in treating opiate
      addiction, but recent studies using extended-release naltrexone injections have
      shown promise. Although no direct comparisons between extended-release naltrexone
      injections and either methadone or buprenorphine exist, indirect comparison of
      retention shows inferior outcome compared with methadone and buprenorphine.
      Further work is needed to directly compare each medication and determine
      individual factors that can assist in medication selection. Until such time,
      selection of medication should be based on informed choice following a discussion
      of outcomes, risks, and benefits of each medication.

PMID- 22873186
TI  - Barriers to drug treatment for IDU couples: the need for couple-based approaches.
AB  - This qualitative study examines the interpersonal and structural barriers to drug
      treatment program entry, retention, and outcomes experienced by injection drug
      using couples, and the program policies regarding injection drug-using couples
      seeking treatment in New York, New York. Our findings reveal a mismatch between
      the substantial need for concurrent and coordinated treatment for partnered
      injection-drug users and programmatic policies that are antithetical to such
      treatment approaches. This discrepancy can be attributed to the lack of viable
      options for couple-focused treatment approaches that fit within the current drug
      treatment system. We provide a rationale and a roadmap for the development of
      innovative approaches for couple-based drug treatment.

PMID- 22873187
TI  - A randomized clinical trial of a therapeutic community treatment for female
      inmates: outcomes at 6 and 12 months after prison release.
AB  - This random assignment study compared female offenders (n = 468) with substance
      use disorders in a prison therapeutic community program with those in a cognitive
      behavioral intervention. The study demonstrates that all women benefitted from
      gender-sensitive prison treatment, but the therapeutic community was more
      effective in reducing drug use, criminal activity, and exposure to trauma and
      increasing mental health functioning and time until reincarceration during the
      year after prison. In addition, the ability to sustain and even improve behavior
      change after the women leave prison highlights the importance of providing
      accessible community-based continuity of mental health and substance abuse
      services during reentry.

PMID- 22873188
TI  - Housing First for severely mentally ill homeless methadone patients.
AB  - The Housing First approach used by Pathways to Housing, Inc., was used to enhance
      residential independence and treatment retention of homeless, seriously mentally
      ill methadone patients. The Keeping Home project first secured scattered-site
      apartments and assertive community treatment services and then addressed
      patients' service needs. Three years post-implementation, methadone treatment
      retention for 31 Keeping Home patients versus 30 comparison participants (drawn
      from an administrative database) was 51.6% vs. 20% (p < .02);
      apartment/independent housing retention was 67.7% vs. 3% or 13% (both p's < .01).
      Although results firmly support Keeping Home, future research needs to address
      study's possible database limitations.

PMID- 22873189
TI  - Opioid maintenance treatment as a harm reduction tool for opioid-dependent
      individuals in New York City: the need to expand access to buprenorphine/naloxone
      in marginalized populations.
AB  - The aim of this pilot study was to assess the effectiveness of
      buprenorphine/naloxone (BUP/NX) among marginalized, opioid-dependent individuals
      in terms of retention in and cycling into and out of a harm-reduction program.
      This pilot study enrolled 100 participants and followed them from November 2005
      to July 2008. The overall proportion of patients retained in the program at the
      end of 3, 6, 9, and 12 months was 68%, 63%, 56%, and 42%, respectively. This
      pilot study demonstrated that BUP/NX could be successfully used to treat
      marginalized heroin users.

PMID- 22873190
TI  - Rate and predictors of employment among formerly polysubstance dependent urban
      individuals in recovery.
AB  - Employment is a key functioning index in addiction services and consistently
      emerges as a goal among individuals in recovery. Research on the employment
      status in the addiction field has focused on treatment populations or welfare
      recipients; little is known of employment rates or their predictors among
      individuals in recovery. This study seeks to fill this gap, capitalizing on a
      sample (N = 311) of urban individuals at various stages of recovery. Fewer than
      half (44.5%) of participants were employed; in logistic regressions, male gender
      and Caucasian race enhanced the odds of employment, whereas having a comorbid
      chronic physical or mental health condition decreased the odds by half.
      Implications center on the need to identify effective strategies to enhance
      employability among women and minorities and for integrated care for individuals
      with multiple chronic conditions.

PMID- 22873191
TI  - Factors associated with mental health clinicians' referrals to 12-Step groups.
AB  - As substance use and mental illness services are increasingly integrated, mental
      health professionals are presented with opportunities to refer greater numbers of
      dually diagnosed clients to 12-Step groups. This study examined the relationships
      among clinicians' 12-Step experiences, attitudes, and referral practices in 6
      mental health clinics in New York, New York. A path analysis model showed that
      greater interest in learning about 12-Step groups directly predicted 12-Step
      referral practices and that 12-Step interest was predicted by clinicians'
      perception of the helpfulness of 12-Step groups and the severity of their
      patients' problems with substance abuse. Clinicians' responses to open-ended
      questions supported this model. Didactic and experiential education for
      clinicians in substance abuse and mutual aid would likely increase patient
      referrals to 12-Step groups.

PMID- 22873192
TI  - Leveraging technology to enhance addiction treatment and recovery.
AB  - Technology such as the Internet and mobile phones offers considerable promise for
      affecting the assessment, prevention, and treatment of and recovery from
      substance use disorders. Technology may enable entirely new models of behavioral
      health care within and outside of formal systems of care. This article reviews
      the promise of technology-based therapeutic tools for affecting the quality and
      reach of addiction treatment and recovery support systems, as well as the
      empirical support to date for this approach. Potential models for implementing
      technology-based interventions targeting substance use disorders are described.
      Opportunities to optimize the effectiveness and impact of technology-based
      interventions targeting addiction and recovery, along with outstanding research
      needs, are discussed.

PMID- 22873193
TI  - President's message.

PMID- 22873194
TI  - Passion flower extract antagonizes the expression of nicotine locomotor
      sensitization in rats.
AB  - CONTEXT: Nicotine, a bioactive component of tobacco, is highly addictive.
      Numerous therapies have been developed or are currently under investigation for
      smoking cessation, and all have met with limited success and/or side effects,
      indicating the need for additional therapies. OBJECTIVE: This study examines the
      ability of a commerically-available aqueous extract of Passiflora incarnata Linn.
      (Passifloraceae) to ameliorate the signs of nicotine sensitization using a rat
      model. MATERIALS AND METHODS: Rats were administered 0.4 mg/kg nicotine or
      vehicle once a day for four consecutive days. Nicotine adminstration produces
      sensitization of locomotor activity, a phenomenon implicated in the development
      of nicotine dependence. On the fifth day, locomotor activity of the subjects was
      monitored as rats from each treatment group were administered 800 mg/kg of
      Passiflora incarnata extract (or its vehicle) followed by a challenge dose of 0.4
      mg/kg nicotine. RESULTS: When given to rats sensitized to nicotine for 4 days,
      the challenge dose of nicotine increased locomotor activity by more than 2-fold
      over activity following nicotine challenge in rats treated with vehicle during
      the sensitization phase. The difference was significant from 15-40 min after
      nicotine administration. Rats sensitized to nicotine then treated with Passiflora
      incarnata extract prior to the nicotine challenge exhibited a level of locomotor
      activity the same as the vehicle-treated controls. DISCUSSION: Passiflora
      incarnata extract did antagonize the expression of nicotine locomotor
      sensitization. CONCLUSION: Passiflora incarnata extract should be examined in
      future studies to evaluate its potential for treating nicotine addiction in
      humans.

PMID- 22873195
TI  - SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute
      myeloid leukemia.
AB  - The molecular pathogenesis underlying the primary myelofibrosis (PMF) progression
      to acute myeloid leukemia (AML) is still not well defined. The involvement of
      microRNA (miRNA) is actually helping to shed light on an important issue in the
      occurrence of myeloproliferative neoplasms (MPNs). However, the role of intronic
      miRNA, derived from the intron regions of gene transcripts, has never been
      reported in MPNs. In this study, we describe a PMF case evolved to AML with a
      t(12;18)(p13;q12) rearrangement showing the downregulation of the intronic
      miR_4319 and the overexpression of its host gene, SET binding protein (SETBP1). A
      possible molecular mechanism regulating the PMF progression to AML is discussed.

PMID- 22873196
TI  - Analyzing the spatial and temporal distribution of human brucellosis in
      Azerbaijan (1995 - 2009) using spatial and spatio-temporal statistics.
AB  - BACKGROUND: Human brucellosis represents a significant burden to public and
      veterinary health globally, including the republic of Azerbaijan. The purpose of
      this study was to examine and describe the spatial and temporal aspects of the
      epidemiology of human brucellosis in Azerbaijan from 1995 to 2009. METHODS: A
      Geographic information system (GIS) was used to identify potential changes in the
      spatial and temporal distribution of human brucellosis in Azerbaijan during the
      study period. Epidemiological information on the age, gender, date, and location
      of incident cases were obtained from disease registries housed at the Republican
      Anti-Plague station in Baku. Cumulative incidences per 100,000 populations were
      calculated at the district level for three, 5-year periods. Spatial and temporal
      cluster analyses were performed using the Local Moran's I and the Ederer-Myer
      Mantel (EMM) test. RESULTS: A total of 7,983 cases of human brucellosis were
      reported during the 15-year study period. Statistically significant spatial
      clusters were identified in each of three, five year time periods with cumulative
      incidence rates ranging from 101.1 (95% CI: 82.8, 124.3) to 203.0 (95% CI; 176.4,
      234.8). Spatial clustering was predominant in the west early in the study during
      period 1 and then in the east during periods 2 and 3. The EMM test identified a
      greater number of statistically significant temporal clusters in period 1 (1995
      to 1999). CONCLUSION: These results suggest that human brucellosis persisted
      annually in Azerbaijan across the study period. The current situation
      necessitates the development of appropriate surveillance aimed at improving
      control and mitigation strategies in order to help alleviate the current burden
      of disease on the population. Areas of concern identified as clusters by the
      spatial-temporal statistical analyses can provide a starting point for
      implementing targeted intervention efforts.

PMID- 22873197
TI  - Tools and procedures for ex vivo vein arterialization, preconditioning and tissue
      engineering: a step forward to translation to combat the consequences of vascular
      graft remodeling.
AB  - The present contribution reviews recent progress in bioengineering approaches
      used to mimic arterial hemodynamic conditions in vascular grafts and vessel
      substitutes used in vascular surgery. While implantation of vascular bypasses is
      still the primary option for cardiac and vascular surgeons to recover blood
      perfusion in cardiac and peripheral ischemic tissues, effective techniques to
      reduce the impact of post-grafting vascular remodeling are insufficient. In our
      view, the design of specific bioreactors to perform vascular conditioning with
      complex stimulation patterns will provide valuable tools for comprehensive
      molecular analysis of vessel arterialization process. In addition, this approach
      will allow the future design of refined protocols to perform pre-conditioning of
      natural vessels, reseeding of human or animalderived decellularized vascular
      grafts or, finally, derivation of fully engineered arterial-compliant
      substitutes, with a reduced remodeling impact.

PMID- 22873198
TI  - Comparison of the distribution and clonal expansion features of the T-cell
      gammadelta repertoire in myelodysplastic syndrome-RAEB and RAEB with progression
      to AML.
AB  - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic
      stem cell diseases. Approximately 30% of patients with MDS will develop acute
      myeloid leukemia (AML). Immune dysregulation may contribute to MDS initiation and
      progression. The altered expression and clonal expansion of the Vbeta repertoire
      were observed in patients with MDS. To further examine the characteristic
      features of gammadelta(+)T cells in MDS, we investigated the distribution pattern
      and clonal expansion capacity of the T-cell receptor (TCR) Vgamma and Vdelta
      repertoire in patients with refractory anemia with excess of blasts (RAEB) and
      compared the difference between groups of patients with RAEB and RAEB-AML. Thirty
      one patients with newly diagnosed MDS-RAEB were enrolled, and 9 of the 31
      patients with RAEB developed AML (RAEB-AML). The TCR Vgamma subfamily expression
      frequencies were similar in the RAEB and RAEB-AML patient groups. The number of
      the TCR Vdelta subfamilies expressed in the RAEB group was higher than that in
      the RAEB-AML group. In most cases, a significantly higher Vdelta4 subfamily
      expression frequency (63.64%, 14/22) could be detected in the RAEB group, whereas
      only 11.11% (1/9) was found in the RAEB-AML group (p=0.0079). At least one
      clonally expanded TCR Vdelta subfamily member was detected in all cases in both
      groups. Vdelta3 was the most frequent clonally expanded T cell subfamily member
      found in the RAEB and RAEB-AML group, while the most frequent clonally expanded T
      cell subfamily member in the RAEB-AML group was Vdelta8 (87.5%, 7/8), which was
      significantly higher than that in the RAEB group (42.86%, 9/21; p=0.0307). In
      conclusion, the TCR Vdelta subfamily expression pattern exhibited a marked
      restriction in patients with RAEB-AML. The lower Vdelta4 frequency and higher
      clonally expanded Vdelta8 T cell alterations were the characteristic features
      found in RAEB-AML. These results provide new data regarding the immunodeficiency
      and immune reactive characteristics of patients with RAEB and RAEB-AML.

PMID- 22873199
TI  - A new resveratrol trimer derivative from Gnetum brunonianum.
AB  - A new resveratrol trimer derivative, named as gnetubrunol A (1), together with
      five known stilbene derivatives, shegansu B (2), resveratrol (3),
      isorhapontigenin (4), gnetifolin E (5), and isorhapontigenin-11-O-beta-d
      glucopyranoside (6) were isolated from the lianas of Gnetum brunonianum Griff.
      Their structures were elucidated on the basis of spectral analysis (UV, IR, MS,
      (1)H NMR, (13)C NMR, and 2D NMR). The anti-inflammatory activities of 1, 5, and 6
      have also been assayed.

PMID- 22873200
TI  - Optimisation of polymer coating process for microencapsulating ferrous fumarate
      for salt double fortification with iodine and iron.
AB  - An extrusion-based encapsulation process has been developed for making salt grain
      sized iron premix for salt fortification. The first step of extrusion
      agglomeration process has been studied and reported previously. The focus of this
      study is on the optimisation of the colour-masking and polymer coating steps.
      Several colour-masking techniques and polymer encapsulants were investigated at
      various encapsulation levels. Salt samples prepared by blending the resulting
      iron premixes with iodised salt retained more than 90% of the original iodine and
      more than 93% of the ferrous iron after 3 months storage at 35 degrees C and 60%
      relative humidity (RH). Hydrophilic coatings such as hydroxypropyl methyl
      cellulose (HPMC) offered more protection at the 10% encapsulation level compared
      to other coating materials studied. All iron premix formulations exhibited high
      particle density, good bioavailability and acceptable organoleptic properties.
      The process using the most effective formulations and optimised operation
      parameters is ready for pilot scale testing and field studies.

PMID- 22873201
TI  - Smoking and early pregnancy thyroid hormone and anti-thyroid antibody levels in
      euthyroid mothers of the Northern Finland Birth Cohort 1986.
AB  - BACKGROUND: Smokers in the general population have lower thyrotropin (TSH) and
      higher free triiodothyronine (fT3) and free thyroxine (fT4) concentrations, but
      the results in pregnant population vary from no effect to a decrease in TSH and
      fT4 concentrations and an increase in fT3 levels. Our objective was to further
      evaluate the question of whether there is an association between smoking, before
      and during pregnancy, with maternal thyroid function during pregnancy and with
      the risk for subsequent hypothyroidism. METHODS: Our study population was a
      prospective population-based cohort (N=9362), the Northern Finland Birth Cohort
      1986, with extensive data throughout gestation. The mothers underwent serum
      sampling in early pregnancy. The samples were assayed for TSH, fT3, fT4, thyroid
      peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Abs) (n=5805).
      Mothers with thyroid dysfunction diagnosed before or during pregnancy were
      excluded, leaving 4837 euthyroid mothers. The smoking status of mothers and
      fathers were requested by questionnaires during pregnancy. Subsequent maternal
      morbidity relating to hypothyroidism 20 years after the index pregnancy was
      evaluated using national registers. RESULTS: Euthyroid mothers who smoked before,
      or continued smoking during first trimester of pregnancy, had higher serum fT3
      (p<0.001) and lower fT4 (p=0.023) concentrations than nonsmokers. Smoking in the
      second trimester was associated with higher fT3 (p<0.001) concentrations, but no
      difference in fT4 concentrations compared with nonsmokers. TG-Abs were less
      common among smoking than nonsmoking mothers (2.5% vs. 4.7%, p<0.001), but the
      prevalence of TPO-Ab was similar. Paternal smoking had no independent effect on
      maternal early pregnancy thyroid hormone or antibody concentrations. The risk of
      subsequent maternal hypothyroidism after follow-up of 20 years was similar among
      prepregnancy smokers and nonsmokers. CONCLUSIONS: In euthyroid women, smoking
      during pregnancy was associated with higher fT3 levels and lower fT4 levels;
      possibly reflecting smoking-induced changes in peripheral metabolism of thyroid
      hormones. No differences were found in TSH concentrations between smokers and
      nonsmokers. Our results differ from those of the general population, which
      usually have shown smoking-induced thyroidal stimulation. This is possibly due to
      pregnancy-induced changes in thyroid function. Decreases in fT4 levels among
      smokers might predispose to hypothyroidism or hypothyroxinemia during pregnancy.
      Despite these changes in thyroid function, smoking did not increase the woman's
      risk of subsequent hypothyroidism.

PMID- 22873202
TI  - 2-h postchallenge plasma glucose predicts cardiovascular events in patients with
      myocardial infarction without known diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: The incidence of cardiovascular events remains high in
      patients with myocardial infarction (MI) despite advances in current therapies.
      New and better methods for identifying patients at high risk of recurrent
      cardiovascular (CV) events are needed. This study aimed to analyze the predictive
      value of an oral glucose tolerance test (OGTT) in patients with acute myocardial
      infarction without known diabetes mellitus (DM). METHODS: The prospective cohort
      study consisted of 123 men and women aged between 31-80 years who had suffered a
      previous MI 3-12 months before the examinations. The exclusion criteria were
      known diabetes mellitus. Patients were followed up over 6.03 +/- 1.36 years for
      CV death, recurrent MI, stroke and unstable angina pectoris. A standard OGTT was
      performed at baseline. RESULTS: 2-h plasma glucose (HR, 1.27, 95% CI, 1.00 to
      1.62; P < 0.05) and smoking (HR, 3.56, 95% CI, 1.02 to 12.38; P < 0.05) proved to
      be independent predictors of CV events in multivariate statistical analysis after
      adjustments for age, sex, total cholesterol, and other baseline characteristics.
      CONCLUSIONS: In this study population, with previous MI and without known DM, 2-h
      PG and smoking were significant predictors of CV death, recurrent MI, stroke and
      unstable angina pectoris, independent of baseline characteristics and medical
      treatment.

PMID- 22873205
TI  - The relationship between cortical auditory evoked potential (CAEP) detection and
      estimated audibility in infants with sensorineural hearing loss.
AB  - OBJECTIVE: To determine the effectiveness of objective statistical detection in
      CAEP testing to evaluate audibility in young infants with sensorineural hearing
      loss. DESIGN: CAEP recordings to speech-based stimuli were made at three
      presentation levels (55, 65, or 75 dB SPL) when a group of hearing-impaired
      infants were either aided or unaided. Later-obtained behavioral audiograms were
      used as the gold standard against which to evaluate the accuracy of the automatic
      detection of the presence/absence of CAEP responses. STUDY SAMPLE: Participants
      were 18 infants with confirmed sensorineural hearing loss. RESULTS: Higher
      sensation levels led to a greater number of present CAEP responses being
      detected. More CAEP waveforms were detected in the aided condition than in the
      unaided condition. CONCLUSION: Our results suggest that the presence/absence of
      CAEP responses defined by the automatic statistical criterion was effective in
      showing whether increased sensation levels provided by amplification were
      sufficient to reach the cortex. This was clearly apparent from the significant
      increase in cortical detections when comparing unaided with aided testing.

PMID- 22873203
TI  - Activation of diverse signaling pathways by ex-vivo delivery of multiple
      cytokines for myocardial repair.
AB  - We tested the hypothesis that simultaneous transgenic overexpression of a select
      quartet of growth factors activates diverse signaling pathways for mobilization
      and participation of various stem/progenitor cells for cardiogenesis in the
      infarcted heart. Human insulin growth factor-1 (IGF-1), vascular endothelial
      growth factor (VEGF), stromal cell-derived factor-1 (SDF-1a), and hepatocyte
      growth factor (HGF) plasmids were synthesized and transfected into skeletal
      myoblasts (SM) from young male wild-type or transgenic rats expressing green
      fluorescent protein (GFP). Overexpression of growth factors in transfected SM
      ((Trans)SM) was confirmed by reverse transcription polymerase chain reaction,
      western blotting, and fluorescence immunostaining. Using our custom-made growth
      factor array and western blotting, multiple angiogenic and prosurvival factors
      were detected in (Trans)SM, including secreted frizzled related protein-1,2,4,5,
      matrix metalloproteinases-3 and 9, connexin-43, netrin-1, Nos-2, Wnt-3, Akt,
      MAPK42/44, Stat3, nuclear factor kappa B (NFkappaB), hypoxia-inducible factor 1
      (HIF-1alpha), and protein kinase C (PKC).   The conditioned medium (CM) from
      (Trans)SM was cytoprotective for cardiomyocytes following H(2)O(2) treatment
      [P<0.01 vs. CM from native SM ((Nat)SM)], promoted a higher transwell migration
      of human umbilical cord vein endothelial cells (223.3+/-1.8, P<0.01) and in vitro
      tube formation (47.8+/-1.9, P<0.01). Intramyocardial transplantation of 1.5*10(6)
      (Trans)SM (group-3) in a rat model of acute myocardial infarction induced
      extensive mobilization of cMet(+), ckit(+), ckit(+)/GATA(4+), CXCR4(+), CD44(+),
      CD31(+), and CD59(+) cells into the infarcted heart on day 7 and improved
      integration of (Trans)SM in the heart compared to (Nat)SM (group 2) (P<0.05).
      Extensive neomyogenesis and angiogenesis in group-3 (P<0.01 vs. group-2), with
      resultant attenuation of infarct size (P<0.01 vs. group-2) and improvement in
      global heart function (P<0.01 vs. group-2) was observed at 8 weeks. In
      conclusion, simultaneous activation of diverse signaling pathways by
      overexpression of multiple growth factors caused massive mobilization and homing
      of stem/progenitor cells from peripheral circulation, the bone marrow, and the
      heart for accelerated repair of the infarcted myocardium.

PMID- 22873206
TI  - Low density lipoprotein receptor-related protein 1 expression correlates with
      cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy
      patients.
AB  - Our hypothesis was that overexpression of certain lipoprotein receptors might be
      related to lipid accumulation in the human ischemic myocardium. Intramyocardial
      lipid overload contributes to contractile dysfunction and arrhythmias in
      cardiomyopathy. Thus, the purpose of this study was to assess the effect of
      hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in
      cardiomyocytes, as well as the potential correlation between LRP1 expression and
      neutral lipid accumulation in the left ventricle tissue from ischemic
      cardiomyopathy patients. Cell culture experiments include control and LRP1
      deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic
      conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts
      (CNT) were included. Low density lipoprotein receptor-related protein 1 (LRP1),
      very low density lipoprotein receptor (VLDLR) and low density lipoprotein
      receptor (LDLR) expression was analyzed by real time PCR and Western blotting.
      Cholesteryl ester (CE), triglyceride (TG) and free cholesterol (FC) content was
      assess by thin layer chromatography following lipid extraction. Western blotting
      experiments showed that protein levels of LRP1, VLDLR and HIF-1alpha were
      significantly upregulated in ischemic hearts. Immunohistochemistry and confocal
      microscopy analysis showed that LRP1 and HIF-1alpha were upregulated in
      cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and
      hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a
      major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes.
      Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic
      hearts. Taken together, our results suggest that LRP1 upregulation is key for
      myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1
      may be a target to prevent the deleterious effects of myocardial cholesterol
      accumulation in ischemic cardiomyopathy.

PMID- 22873207
TI  - Early functional results after hemiarthroplasty for femoral neck fracture: a
      randomized comparison between a minimal invasive and a conventional approach.
AB  - BACKGROUND: A minimal invasive approach for elective hip surgery has been
      implemented in our institution in the past. It is widely hypothesized that
      implanting artificial hips in a minimal invasive fashion decreases surgical
      trauma and is helpful in the rehabilitation process in elective hip surgery.
      Thereby geriatric patients requiring emergency hip surgery also could
      theoretically benefit from a procedure that involves less tissue trauma. METHODS:
      Sixty patients who sustained a fractured neck of femur were randomly assigned
      into two groups. In the minimal invasive arm, the so called "direct anterior
      approach" (DAA) was chosen, in the conventional arm the Watson-Jones-Approach was
      used for implantation of a bipolar hemi-arthroplasty.Primary outcome parameter
      was the mobility as measured by the four-item-Barthel index. Secondary outcome
      parameters included pain, haemoglobin-levels, complications, duration of surgery,
      administration of blood transfusion and external length of incision. Radiographs
      were evaluated. RESULTS: A statistically significant difference (p = 0,009)
      regarding the mobility as measured with the four-item Barthel index was found at
      the 5th postoperative day, favouring the DAA. Evaluation of the intensity of pain
      with a visual analogue scale (VAS) showed a statistically significant difference
      (p = 0,035) at day 16. No difference was evident in the comparison of
      radiographic results. CONCLUSIONS: Comparing two different approaches to the hip
      joint for the implantation of a bipolar hemi-arthroplasty after fractured neck of
      femur, it can be stated that mobilization status is improved for the DAA compared
      to the WJA when measured by the four-item Barthel index, there is less pain as
      measured using the VAS. There is no radiographic evidence that a minimal invasive
      technique leads to inferior implant position. LEVEL OF EVIDENCE: Level II
      therapeutic study.

PMID- 22873209
TI  - Physical-chemical and microbiological changes in Cerrado Soil under differing
      sugarcane harvest management systems.
AB  - BACKGROUND: Sugarcane cultivation plays an important role in Brazilian economy,
      and it is expanding fast, mainly due to the increasing demand for ethanol
      production. In order to understand the impact of sugarcane cultivation and
      management, we studied sugarcane under different management regimes (pre-harvest
      burn and mechanical, unburnt harvest, or green cane), next to a control treatment
      with native vegetation. The soil bacterial community structure (including an
      evaluation of the diversity of the ammonia oxidizing (amoA) and denitrifying
      (nirK) genes), greenhouse gas flow and several soil physicochemical properties
      were evaluated. RESULTS: Our results indicate that sugarcane cultivation in this
      region resulted in changes in several soil properties. Moreover, such changes are
      reflected in the soil microbiota. No significant influence of soil management on
      greenhouse gas fluxes was found. However, we did find a relationship between the
      biological changes and the dynamics of soil nutrients. In particular, the burnt
      cane and green cane treatments had distinct modifications. There were significant
      differences in the structure of the total bacterial, the ammonia oxidizing and
      the denitrifying bacterial communities, being that these groups responded
      differently to the changes in the soil. A combination of physical and chemical
      factors was correlated to the changes in the structures of the total bacterial
      communities of the soil. The changes in the structures of the functional groups
      follow a different pattern than the physicochemical variables. The latter might
      indicate a strong influence of interactions among different bacterial groups in
      the N cycle, emphasizing the importance of biological factors in the structuring
      of these communities. CONCLUSION: Sugarcane land use significantly impacted the
      structure of total selected soil bacterial communities and ammonia oxidizing and
      denitrifier gene diversities in a Cerrado field site in Central Brazil. A high
      impact of land use was observed in soil under the common burnt cane management.
      The green cane soil also presented different profiles compared to the control
      soil, but to at a lesser degree.

PMID- 22873208
TI  - Untangling the evolution of Rab G proteins: implications of a comprehensive
      genomic analysis.
AB  - BACKGROUND: Membrane-bound organelles are a defining feature of eukaryotic cells,
      and play a central role in most of their fundamental processes. The Rab G
      proteins are the single largest family of proteins that participate in the
      traffic between organelles, with 66 Rabs encoded in the human genome. Rabs direct
      the organelle-specific recruitment of vesicle tethering factors, motor proteins,
      and regulators of membrane traffic. Each organelle or vesicle class is typically
      associated with one or more Rab, with the Rabs present in a particular cell
      reflecting that cell's complement of organelles and trafficking routes. RESULTS:
      Through iterative use of hidden Markov models and tree building, we classified
      Rabs across the eukaryotic kingdom to provide the most comprehensive view of Rab
      evolution obtained to date. A strikingly large repertoire of at least 20 Rabs
      appears to have been present in the last eukaryotic common ancestor (LECA),
      consistent with the 'complexity early' view of eukaryotic evolution. We were able
      to place these Rabs into six supergroups, giving a deep view into eukaryotic
      prehistory. CONCLUSIONS: Tracing the fate of the LECA Rabs revealed extensive
      losses with many extant eukaryotes having fewer Rabs, and none having the full
      complement. We found that other Rabs have expanded and diversified, including a
      large expansion at the dawn of metazoans, which could be followed to provide an
      account of the evolutionary history of all human Rabs. Some Rab changes could be
      correlated with differences in cellular organization, and the relative lack of
      variation in other families of membrane-traffic proteins suggests that it is the
      changes in Rabs that primarily underlies the variation in organelles between
      species and cell types.

PMID- 22873210
TI  - The effect of interactive neurostimulation therapy on myofascial trigger points
      associated with mechanical neck pain: a preliminary randomized, sham-controlled
      trial.
AB  - OBJECTIVES: This trial was conducted to assess the effectiveness of interactive
      neurostimulation (INS) therapy on the treatment of pain associated with
      myofascial trigger points (MTPs) in adults with mechanical neck pain. DESIGN:
      This was a preliminary, randomized, sham-controlled trial. SETTING: The trial was
      conducted in a tertiary-care institution. SUBJECTS: The participants were 23
      adults with pain and MTPs in the neck or shoulder lasting>2 weeks. INTERVENTIONS:
      INS (active or sham) was delivered for 10 minutes in a single session over the
      MTP area in each patient. OUTCOME MEASURES: Immediately following the
      intervention, subjects were tested for pressure pain thresholds (PPTs) and 10-cm
      visual analogue scale score (VAS) for pain intensity. At the 5 day follow-up, two
      additional tests were performed: the neck disability index (NDI) and the patient
      specific functional scale (PSFS) for function. RESULTS: Improvements in function
      (PSFS) were observed in the treatment group, which were of clinical significance
      in selected subjects. These effects were statistically greater than those
      obtained in the sham group but were overall not at a level of clinical
      significance in this small population. Improvements in pain intensity (VAS) and
      neck disability (NDI) were observed in both the treatment and sham groups,
      indicating that INS had no greater benefit using these measures. There was no
      change in PPTs following either the active or sham treatment. CONCLUSIONS: INS is
      a new and emerging therapy, which may be efficacious for managing musculoskeletal
      conditions, such as myofascial pain syndrome. This study demonstrated
      improvements in function in individuals with MTPs following INS therapy, which
      may be of clinical significance in certain patients with neck or shoulder pain.
      Further large-scale clinical trials are required to confirm this effect and to
      determine if INS also reduces pain and neck disability.

PMID- 22873211
TI  - Transcriptional heterochrony in talpid mole autopods.
AB  - BACKGROUND: Talpid moles show many specializations in their adult skeleton linked
      to fossoriality, including enlarged hands when compared to the feet. Heterochrony
      in developmental mechanisms is hypothesized to account for morphological
      evolution in skeletal elements. METHODS: The temporal and spatial distribution of
      SOX9 expression, which is an early marker of chondrification, is analyzed in
      autopods of the fossorial Iberian mole Talpa occidentalis, as well as in shrew
      (Cryptotis parva) and mouse (Mus musculus) for comparison. RESULTS AND
      DISCUSSION: SOX9 expression is advanced in the forelimb compared to the hind limb
      in the talpid mole. In contrast, in the shrew and the mouse, which do not show
      fossorial specializations in their autopods, it is synchronous. We provide
      evidence that transcriptional heterochrony affects the development of talpid
      autopods, an example of developmental penetrance. We discuss our data in the
      light of earlier reported pattern heterochrony and later morphological variation
      in talpid limbs. CONCLUSION: Transcriptional heterochrony in SOX9 expression is
      found in talpid autopods, which is likely to account for pattern heterochrony in
      chondral limb development as well as size variation in adult fore- and hind
      limbs.

PMID- 22873212
TI  - Monitoring in vitro thrombus formation with novel microfluidic devices.
AB  - Cardiovascular disease is a major cause of mortality globally and is subject to
      ongoing research to improve clinical treatment. It is established that activation
      of platelets and coagulation are central to thrombosis, yet at different extents
      in the arterial and venous system. In vitro perfusion chamber technology has
      contributed significant knowledge on the function of platelets in the thrombotic
      process under shear conditions. Recent efforts to downscale this technique with a
      variety of microfluidic devices has opened new possibilities to study this
      process under precisely controlled flow conditions. Such microfluidic devices
      possess the capability to execute platelet function tests more quickly than
      current assays, while using small blood samples. Gradually becoming available to
      the clinic now, they may provide a new means to manage the treatment of
      cardiovascular diseases, although accurate validation studies still are missing.
      This review highlights the progress that has been made in monitoring aspects of
      thrombus formation using microfluidic devices.

PMID- 22873213
TI  - Targeted anti-leukemic therapy as disease-stabilizing treatment for acute myeloid
      leukemia relapse after allogeneic stem cell transplantation: Will it be possible
      to combine these strategies with retransplantation or donor lymphocyte infusions?
AB  - Allogeneic stem cell transplantation is commonly used in the treatment of high
      risk acute myeloid leukemia (AML). This intensive treatment has a high early
      transplant-related mortality, and an additional significant cause of death in
      these patients is later AML relapse. Retransplantation can be considered for a
      minority of patients, but only 10-20% of selected patients then achieve long-term
      survival. Donor lymphocyte infusion (DLI) has an antileukemic effect, but the
      effect of this treatment usually lasts for only 3-4 months. A possible strategy
      to improve the prognosis could be to combine antileukemic T-cell therapy (i.e.
      DLI) with AML-targeting therapy. Several aspects have to be considered for such
      approaches: (i) the therapy should have immunomodulatory rather than
      immunosuppressive effects; (ii) the regimen should have a low hematological
      toxicity to preserve residual normal bone marrow function; and (iii) the
      treatment should have a documented antileukemic effect. DLI elicit both graft
      versus host and graft versus leukemia effects, and could be added to
      pharmacological treatment. Epigenetic targeting should be considered in these
      patients because both demethylating agents as well as the histone deacetylase
      inhibitors have documented antileukemic effects and have a relatively low
      hematological toxicity. Other drugs to consider are thalidomide, lenalidomide,
      antiangiogenic agents, tyrosine kinase inhibitors and heat shock protein 90
      inhibitors, which all have both antileukemic and immunomodulatory effects.
      Relatively few clinical studies are available for patients with this high-risk
      disease. The designs of future clinical trials have to carefully consider the
      antileukemic and immunomodulatory effects together with the risk of especially
      hematological toxicity.

PMID- 22873214
TI  - Role of acyclic retinoid in the chemoprevention of hepatocellular carcinoma:
      basic aspects, clinical applications, and future prospects.
AB  - The poor prognosis for hepatocellular carcinoma (HCC) is associated with its high
      rate of recurrence in the cirrhotic liver. Therefore, development of effective
      strategies for preventing recurrence and secondary tumors will improve the
      clinical outcome of HCC patients. A malfunction of the retinoid X receptor-alpha
      (RXRalpha) due to phosphorylation by the Ras-MAPK signaling pathway is profoundly
      associated with liver carcinogenesis, and thus, may be a promising target for HCC
      chemoprevention. Acyclic retinoid (ACR), which inhibits Ras-MAPK activation and
      RXRalpha phosphorylation, successfully prevents HCC recurrence, thus improving
      patient survival. The fundamental concept of HCC chemoprevention by ACR is
      "clonal deletion," which is defined as the removal of latent malignant clones
      from the liver before they expand into clinically detectable HCC. "Combination
      chemoprevention" using ACR as a key drug holds great promise of a new effective
      strategy for the prevention of HCC because of its synergism. ACR is also expected
      to prevent the development of HCC in obese people, who are at an increased risk
      to HCC, because this agent significantly inhibits obesity-related liver
      tumorigenesis in the rodent model. Here, we review the detailed effects of ACR on
      preventing HCC development, especially based on the results of our basic and
      clinical research.

PMID- 22873215
TI  - Non-coding RNAs as therapeutic targets in hepatocellular cancer.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy that affects a large number
      of patients worldwide, with an increasing incidence in the United States and
      Europe. The therapies that are currently available for patients with inoperable
      HCC have limited benefits. Although molecular targeted therapies against selected
      cell signaling pathways have shown some promising results, their impact has been
      minimal. There is a need to identify and explore other targets for the
      development of novel therapeutics. Several non-protein coding RNAs (ncRNA) have
      recently been implicated in hepatocarcinogenesis and tumor progression. These
      ncRNA genes represent promising targets for cancer. However, therapeutic
      targeting of ncRNA genes has not been employed for HCC. The use of antisense
      oligonucleotides and viral vector delivery approaches have been shown to be
      feasible approaches to modulate ncRNA expression. HCC is an optimal cancer to
      evaluate novel RNA based therapeutic approaches because of the potential of
      effective delivery and uptake of therapeutic agents to the liver. In this review,
      we discuss selected ncRNA that could function as potential targets in HCC
      treatment and outline approaches to target ncRNA expression. Future challenges
      include the need to achieve site-specific targeting with acceptable safety and
      efficacy.

PMID- 22873216
TI  - Chemoprevention of hepatocarcinogenesis with dietary isoprenic derivatives:
      cellular and molecular aspects.
AB  - Bioactive food components (BFACs) represent promising candidates for liver cancer
      chemoprevention. Among them, isoprenic derivatives (carotenoids, retinoids,
      perillyl alcohol, limonene, geraniol, farnesol, geranylgeraniol and beta- ionone)
      can be highlighted. The relevance of animal models for the investigation of
      chemopreventive agents is supported by comparative functional genomic studies
      that reinforce the similarities between rodent and human hepatocarcinogenesis.
      Thus, characterization of BFACs in animal models as blocking and/or suppressing
      agents allows the establishment of the theoretical basis for the development of
      chemoprevention strategies. Dietary isoprenic derivatives actions on
      hepatocarcinogenesis may involve a block in carcinogen activation, induction of
      phase 2 enzymes and an antioxidant activity, as well as interference with
      cellular processes including cell communication, proliferation, apoptosis,
      differentiation and remodeling of preneoplastic lesions. Dietary isoprenic
      derivatives modulate molecular targets including HMG-CoA-reductase, Rho, nuclear
      receptors, c-myc, connexin 43, NF-kappaB and Nrf2. Several networks related to
      these targets are altered in early phases of hepatocarcinogenesis. This
      emphasizes the importance of such agents for the chemoprevention of
      hepatocellular carcinoma. Combinations of isoprenic derivatives or of these
      substances with other BFACs classes should be further investigated. Also,
      toxicity and bioavailability and pharmacokinetic aspects of these derivatives
      represent relevant issues in their development as chemopreventive agents. One
      major current limitation of the adoption of dietary isoprenic derivatives for
      liver cancer chemoprevention is the challenge in overcoming the initial
      preclinical phase in agent development. Dietary isoprenic derivatives that
      present liver cancer chemopreventive properties should be further explored in
      clinical trials, begining with the phase 0 approach.

PMID- 22873217
TI  - Role of NF-kappaB in hepatocarcinogenesis and its potential inhibition by dietary
      antioxidants.
AB  - In this review, the role of nuclear factor-kappaB (NF-kappaB) in
      hepatocarcinogenesis is examined. The administration of several hepatic tumor
      promoters leads to the activation of NF-kappaB in the liver of rats and mice.
      Many studies support the hypothesis that the activation of NF-kappaB in the liver
      is inhibited by antioxidants. The role of NF-kappaB in hepatocarcinogenesis has
      been examined using NF-kappaB overexpression and knockout models. The role of NF
      kappaB in liver carcinogenesis is complex; some models show that NF-kappaB
      contributes to carcinogenesis whereas others see no effect or an inhibition.
      Overall, although hepatic tumor promoting agents can activate NF-kappaB and this
      activation can be inhibited by antioxidants, the significance of this activation
      is unclear.

PMID- 22873218
TI  - Anti-tumor efficacy of a recombinant human arginase in human hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is considered as auxotrophic for arginine and BCT
      100, a new recombinant human arginase, has been synthesized for arginine
      deprivation to inhibit arginine-dependent tumor growth. The aim of the present
      study was to evaluate the effects of BCT-100 on the inhibition of in vitro cell
      proliferation of HCC cell lines and in vivo tumor growth. The molecular mechanism
      involved was also studied. The anti-tumor efficacy of BCT-100 on cell
      proliferation, cell cycle distribution and cellular apoptosis were determined in
      human hepatoma HepG2 and PLC/PRF/5 cells. Protein expression in the Wnt/beta
      catenin and Akt signaling pathways were analyzed by western blotting. Tumors were
      also established subcutaneously and BCT-100, in combination with oxaliplatin, was
      administrated i.p. to study the anti-tumor growth of the drugs. Treatment with
      BCT-100 was found to inhibit cell proliferation and enhance caspasedependent
      cellular apoptosis. Cell cycle arrest at S phase was observed. Inhibition of
      Wnt/beta-catenin and Akt signaling pathways, with a reduction in survivin and
      XIAP protein expressions, were also observed. Furthermore, combined treatment of
      BCT-100 and chemotherapy with oxaliplatin demonstrated synergistic inhibiting
      effect on tumor growth and the overall survival probability was enhanced as
      compared with BCT-100 or oxaliplatin treatment alone. These preclinical data
      demonstrate robust anti-tumor activity of BCT100 in HCC, thus providing the basis
      for its exploitation as a potential therapeutic agent in arginine-driven tumors.
      The positive effect of testing BCT100 with oxaliplatin in PLC/PRF/5 tumours also
      supports the rationale of combining BCT-100 and oxaliplatin in the clinical
      treatment of HCC.

PMID- 22873219
TI  - Cancer stem cell as a potential therapeutic target in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human cancers. HCC is a
      chemoresistant cancer and the current drug therapy has limited efficacy. As a
      result, the prognosis of HCC patients is generally poor. Recent studies have
      demonstrated that a subpopulation of cancer cells with stem cell properties,
      called cancer stem cells (CSCs), are responsible for growth and metastasis of
      cancer. CSCs characterized by several markers including CD133, CD44, CD90, OV6,
      Epithelial cell adhesion molecule (EpCAM) and CD13 have been isolated from
      different human HCC cell lines or specimens. CSCs share many of the signaling
      pathways found in normal stem cells, such as Wnt, Hedgehog, Notch and
      Transforming growth factor-beta (TGF-beta) pathways. These pathways are involved
      in self-renewal, differentiation and survival of CSCs. There is evidence of
      deregulation of these pathways in HCC CSCs. MicroRNAs also play an important role
      in regulating signaling pathways in HCC, and recent data suggested an important
      role of microRNA in CSCs of HCC. Therapeutic targeting of CSCs may provide a
      novel strategy that is more effective than the current drugs targeting the bulk
      mature cancer cells in treatment of HCC.

PMID- 22873220
TI  - Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated
      antioxidant mechanisms in a rat model of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers
      with almost > 1 million deaths reported annually worldwide, remains a devastating
      disease with no known effective cure. Hence, chemopreventive strategies come into
      play, offering an effective and safe mode of treatment, ideal to ward off
      potential cancer risks and mortality. A major predisposing condition, pertinent
      to the development and progression of HCC is oxidative stress. We previously
      reported a striking chemopreventive effect of anthocyanin-rich black currant skin
      extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis
      in rats. The current study aims to elucidate the underlying antioxidant
      mechanisms of black currant anthocyanins implicated in the previously observed
      chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE
      (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA
      challenge decreased abnormal lipid peroxidation, protein oxidation, and
      expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT)
      in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated
      the gene expression of a number of hepatic antioxidant and carcinogen detoxifying
      enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and
      uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated
      animals. Protein and mRNA expressions of nuclear factor E2-related factor 2
      (Nrf2) were substantially elevated with BCSE treatment, providing a direct
      evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway,
      which led to the upregulation of a variety of housekeeping genes. The results of
      our study provide substantial evidence that black currant bioactive anthocyanins
      exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by
      attenuating oxidative stress through activation of Nrf2 signaling pathway.

PMID- 22873221
TI  - Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention
      and therapy.
AB  - Hepatocellular carcinoma (HCC) remains one of the most lethal cancers in the
      world. Since current treatment options including surgical resection and liver
      transplantation offer limited therapeutic benefits, there exists a need to
      evaluate novel therapeutic strategies for the amelioration of HCC. Hepatic tumors
      are highly vascularized, possessing a rich network of blood vessels and
      capillaries and there exist an angiogenic component to the tumor growth observed
      in HCC. Thus, anti-angiogenic therapy has been suggested to possess tremendous
      therapeutic potential in the treatment of HCC. The process of angiogenesis
      involves multiple biochemical checkpoints and signaling steps, and thus providing
      a multitude of opportunities for therapeutic intervention. In this review, we
      highlight the role of angiogenesis and its use as a therapeutic strategy for HCC.
      The first part of the article reviews the angiogenic mechanisms with particular
      emphasis on the multitude of biochemical factors, such as receptors, enzymes and
      cytokines involved in the complex interplay of new capillary growth. Next, we
      present the pre-clinical studies which elucidate the anti-angiogenic effects of
      both dietary and non-dietary agents in animal models of HCC. Of particular
      interest is the examination of the effects of the antiangiogenic agents on the
      various angiogenic markers in the hepatic tissue of the animal challenged either
      with a hepatocarcinogen or xenografted with hepatic neoplastic cells. The review
      also highlights the clinical investigations carried out in HCC patients to
      evaluate the therapeutic potential of pharmacological agents with proven anti
      angiogenic properties. Finally, the future directions as well as the benefits and
      potential challenges involved in the use of antiangiogenic pharmacotherapy in the
      treatment of HCC are also discussed.

PMID- 22873222
TI  - Dietary phytochemicals in the chemoprevention and treatment of hepatocellular
      carcinoma: in vivo evidence, molecular targets, and clinical relevance.
AB  - Hepatocellular carcinoma (HCC), one of the most common and lethal cancers, is a
      growing menace in modern society. Until recently, the majority of detected cases
      of liver cancer have been found in the developing nations of Asia and Africa;
      however, its occurrence has significantly increased in the United States. HCC
      occurs due to several etiologies, such as alcoholism, dietary carcinogens, iron
      overload, viral hepatitis, as well as several hepatic chronic diseases. In view
      of the limited treatment options, such as surgery and transplantation, a critical
      need exists to examine alternative approaches. The use of phytochemicals obtained
      from dietary sources provides a novel and fascinating preventive and therapeutic
      approach against HCC. Dietary phytochemicals possess potent antioxidant and anti
      inflammatory properties which are extremely critical to combat the significant
      oxidative stress and inflammation implicated in liver cancer. An impressive
      number of phytochemicals have shown considerable promise as candidates for the
      prevention and treatment of HCC. In this article, we systematically review the in
      vivo pre-clinical evidence documenting the chemopreventive and therapeutic
      potential of several important dietary phytochemicals in HCC. This review
      critically examines the molecular mechanisms of the pharmacological effects of
      the aforementioned animal studies. Clinical and epidemiological studies are also
      highlighted in this review. Emerging issues such as bioavailability, dose
      optimization, targeted drug delivery, role of botanical extracts and synergy are
      also discussed. Finally, current challenges, limitations, future directions,
      innovative concepts and novel hypotheses for the use of dietary phytochemicals in
      the chemoprevention and amelioration of human HCC are presented.

PMID- 22873279
TI  - Development and external validation of a new PTA assessment scale.
AB  - BACKGROUND: Post-traumatic amnesia (PTA) is a key symptom of traumatic brain
      injury (TBI). Accurate assessment of PTA is imperative in guiding clinical
      decision making. Our aim was to develop and externally validate a short, examiner
      independent and practical PTA scale, by selecting the most discriminative items
      from existing scales and using a three-word memory test. METHODS: Mild, moderate
      and severe TBI patients and control subjects were assessed in two separate
      cohorts, one for derivation and one for validation, using a questionnaire
      comprised of items from existing PTA scales. We tested which individual items
      best discriminated between TBI patients and controls, represented by sensitivity
      and specificity. We then created our PTA scale based on these results. This new
      scale was externally evaluated for its discriminative value using Receiver
      Operating Characteristic (ROC) analysis and compared to existing PTA scales.
      RESULTS: The derivation cohort included 126 TBI patients and 31 control subjects;
      the validation cohort consisted of 132 patients and 30 controls. A set of seven
      items was eventually selected to comprise the new PTA scale: age, name of
      hospital, time, day of week, month, mode of transport and recall of three words.
      This scale demonstrated adequate discriminative values compared to existing PTA
      scales on three consecutive administrations in the validation cohort. CONCLUSION:
      We introduce a valid, practical and examiner independent PTA scale, which is
      suitable for mild TBI patients at the emergency department and yet still valuable
      for the follow-up of more severely injured TBI patients.

PMID- 22873280
TI  - Role of chronic E. coli infection in the process of bladder cancer- an
      experimental study.
AB  - BACKGROUND: Bladder cancer is a common malignancy in Egypt. A history of urinary
      tract infection can be considered as a risk factor for bladder cancer.
      Escherichia coli (E. coli) infection is responsible for 70% of urinary tract
      infection. This study aimed to evaluate the role of chronic E. coli infection
      during bladder carcinogenesis. In order to achieve this aim, we investigated the
      histopathological changes in bladder tissue and measured the level of nuclear
      factor kappa p65 (NF-kappaBp65), Bcl-2 and interleukin 6 (IL-6) in four groups
      each consisting of 25 male albino rats except of control group consisting of 20
      rats. The first group was normal control group, the second group was infected
      with E. coli, the third group was administered nitrosamine precursor, and the
      forth group was infected with E. coli and administered nitrosamine precursor.
      RESULTS: The histopathological examination revealed that E. coli infected group
      was able alone to produce some histopathological changes in bladder tissue and
      that nitrosamine precursor plus E. coli group showed highest incidences of
      urinary bladder lesions than the nitrosamine precursor group. NF-kappaBp65, Bcl-2
      and IL-6 levels were significantly higher in nitrosamine precursor plus E. coli
      group than the other groups. CONCLUSION: These findings suggested that urinary
      bladder infection by E. coli may play a major additive and synergistic role
      during bladder carcinogenesis.

PMID- 22873281
TI  - Solution processed aluminum paper for flexible electronics.
AB  - As an alternative to vacuum deposition, preparation of highly conductive papers
      with aluminum (Al) features is successfully achieved by the solution process
      consisting of Al precursor ink (AlH(3){O(C(4)H(9))(2)}) and low temperature
      stamping process performed at 110  degrees C without any serious hydroxylation
      and oxidation problems. Al features formed on several kinds of paper substrates
      (calendar, magazine, and inkjet printing paper substrates) are less than ~60 nm
      thick, and their electrical conductivities were found to be as good as thermally
      evaporated Al film or even better (<=2 Omega/?). Strong adhesion of Al features
      to paper substrates and their excellent flexibility are also experimentally
      confirmed by TEM observation and mechanical tests, such as tape and bending
      tests. The solution processed Al features on paper substrates show different
      electrical and mechanical performance depending on the paper type, and inkjet
      printing paper is found to be the best substrate with high and stable electrical
      and mechanical properties. The Al conductive papers produced by the solution
      process may be applicable in disposal paper electronics.

PMID- 22873282
TI  - Enantioselective synthesis of tetranuclear quadruple helicates.
AB  - Quadruple helical structures are assembled around a tetranuclear cubane structure
      using four chiral tridentate ligands and two ligands coordinating diagonally
      across a face. Stereoselectivity in the complex formation is observed.

PMID- 22873283
TI  - Cobalt-catalyzed ortho-arylation of aromatic imines with aryl chlorides.
AB  - An ortho-arylation reaction of aromatic imines with aryl chlorides has been
      achieved using a cobalt-N-heterocyclic carbene catalyst in combination with a
      neopentyl Grignard reagent. The reaction takes place at room temperature to
      afford biaryl products in moderate to good yields.

PMID- 22873284
TI  - Pregnancy and delivery outcomes following a pathological second trimester triple
      test screening result and a normal karyotype.
AB  - OBJECTIVE: To investigate whether obstetrical complications are increased in
      pregnancies with a normal karyotype and an abnormal triple test (TT) (>=1:380 or
      more) where all analytes were within the normal range. METHODS: A retrospective
      cohort study of women who underwent a TT and delivered in a tertiary medical
      center, was conducted. Patients were divided into a study group (pregnancies with
      abnormal TT) and a control group (normal TT). In both groups, the analyte
      concentrations were within the normal range and the karyotype was normal.
      Demographic and clinical characteristics, antenatal factors, gestational
      complications and perinatal outcomes were compared between the groups. RESULTS:
      An abnormal TT result in the presence of normal analytes and a normal karyotype,
      had no impact on obstetrical complications. A direct association between elevated
      values of hCG within the normal range (0-2.0 MoM) and pathological TT was noticed
      (OR = 2.6, p < 0.01). On the other hand, an inverse correlation between elevation
      in AFP (0-2.0 MoM) and uE3 was found (OR < 0.01, p < 0.01; OR < 0.01, p < 0.01,
      respectively). CONCLUSIONS: An abnormal TT result in the presence of normal
      analytes and a normal karyotype, had no influence on rate of obstetrical
      complications.

PMID- 22873285
TI  - Social strain and executive function across the lifespan: the dark (and light)
      sides of social engagement.
AB  - We investigated how the association between social strain and cognitive
      efficiency varies with task demands across adulthood, from latencies on simpler
      speeded tasks to tests involving executive function. Participants (N = 3280) were
      drawn from the MIDUS survey, a large, diverse national sample of adults who
      completed cognitive tests including speeded task-switching (Tun & Lachman, 2008,
      Developmental Psychology, 44, 1421). After controlling for demographic and health
      variables, we found that higher levels of reported social strain were associated
      with slower processing speed, particularly for the complex task-switching test
      relative to simpler speeded tests. Effects of strain were greatest for those with
      the lowest general cognitive ability. Moreover, those with very high levels of
      social strain but low levels of social support gave the poorest task-switching
      performance. These findings provide further evidence for the complex relationship
      between the social environment and cognition across adulthood, particularly the
      association between efficiency of executive functions and negative social
      interactions.

PMID- 22873286
TI  - Two new compounds from Senecio cannabifolius.
AB  - Chemical investigation of the water extracts from the Senecio cannabifolius Less.
      led us to find two new compounds (1 and 2), along with 12 known compounds (3-14).
      The two new compounds were determined as (E, 4R)-4-hydroxy-4,5,5-trimethyl-3-(3
      oxobut-1-enyl)cyclohex-2-enone (1) and (E)-4-((1S, 3R, 4R)-1-hydroxy-4,5,5
      trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl)but-1-en-3-o-ne (2), respectively. The
      structures of other compounds were elucidated by extensive analysis of spectral
      data and in comparison with the literature values. Compounds 1 and 2 were
      evaluated for inhibitory activity against lipopolysaccharide-induced NO
      production in RAW 264.7 macrophages, and compound 1 showed potent inhibitory
      activity with IC(50) value of 30.65 MUM.

PMID- 22873287
TI  - Asthma medication is increasingly prescribed for finnish olympic athletes--for a
      reason?
AB  - BACKGROUND: Use of asthma medication is common among athletes. In 2009, the World
      Anti-Doping Committee (WADA) and the International Olympic Committee removed the
      need to document asthma by lung function tests before the use of inhaled beta2
      agonists. METHODS: We assessed the changes in asthma medication use in Finnish
      Olympic athletes 8 years apart in 2002 (N = 446) and 2009 (N = 372). The athletes
      filled out a questionnaire on asthma symptoms, diagnosis, and medication.
      RESULTS: The use of asthma medication increased from 9.4% in 2002 to 12.6% in
      2009 (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) 1.08-2.69).
      Fixed combinations of inhaled long-acting beta2-agonists (LABAs) and inhaled
      corticosteroids (ICSs) were used three times more in 2009 vs. 2002 (OR = 3.38,
      95% CI 1.26-9.12). At the same time, no significant changes were observed in the
      occurrences of physician-diagnosed asthma (13.9% vs. 15.9%) or wheezing (10.3%
      vs. 10.2%). In 2002, all athletes on asthma medication also had a physician
      diagnosed disease, but in 2009, 11.8% of the athletes on medication were lacking
      it. CONCLUSIONS: Especially, the use of combination therapy of LABAs and ICSs is
      increasing among Finnish Olympic athletes. This trend is worrying as it is not
      based on increasing occurrence of symptoms, asthma diagnoses, or objective lung
      function measurements. More data, also from other countries, are needed to change
      recommendations or WADA rules.

PMID- 22873288
TI  - Nanoparticles-mediated drug delivery approaches for cancer targeting: a review.
AB  - Cancer has become the leading cause of death among different populations of the
      world. The treatment is limited to chemotherapy, radiation, and surgery.
      Selective targeting to the tumor cells is possible by nanoparticles-based drug
      delivery system. It maximizes the drug concentration at the desired target and
      protects the surrounding healthy tissues at the same time. To improve the
      targeting potential of the anticancer drugs, nanoparticles were optimized for the
      size and surface characteristics to enhance their circulation time and targeting
      efficiency. Passive targeting involves surface modification with polyethylene
      glycol to avoid its elimination by natural body defense mechanism. Active
      targeting involves chemical interaction with certain antigen, receptors, and
      genes which are over expressed during progression of disease. In addition, the
      article highlights recent developments in "smart"-stimulus-responsive-drug
      carriers designed to enhance the localization and efficacy of therapeutic
      payloads as compared with free drug. Enhanced targeting potential, imaging, and
      controlled release of drugs or therapeutic molecules could be possible through
      multi-functional nanocarrier. Such multi-faceted, versatile nanocarriers and drug
      delivery systems promise a substantial increase in the efficacy of diagnostic and
      therapeutic applications in pharmaceutical sciences.

PMID- 22873289
TI  - Molecular evidence for increased antitumor activity of gemcitabine in combination
      with a cyclin-dependent kinase inhibitor, P276-00 in pancreatic cancers.
AB  - BACKGROUND: P276-00 is a novel cyclin-dependent kinase inhibitor currently in
      Phase II clinical trials. Gemcitabine is a standard of care for the treatment of
      pancreatic cancer. The present study investigated the effect of the combination
      of P276-00 and gemcitabine in five pancreatic cancer cell lines. METHODS:
      Cytotoxic activity was evaluated by Propidium Iodide assay. Cell cycle and
      apoptosis was analyzed by flow cytometry. Genes and proteins known to inhibit
      apoptosis and contribute to chemoresistance were analysed using western blot
      analysis and RT-PCR. In vivo efficacy was studied in PANC-1 xenograft model.
      RESULTS: The combination of gemcitabine followed by P276-00 was found to be
      highly to weakly synergistic in various pancreatic cancer cell lines as assessed
      by the combination index. Enhancement of apoptosis in PANC-1 cells and decrease
      in the antiapoptotic protein Bcl-2 and survivin was seen. P276-00 potentiated the
      gemcitabine-induced cytotoxicity by modulation of proteins involved in
      chemoresistance to gemcitabine and cell cycle viz. antiapoptotic proteins p8 and
      cox-2, proapoptotic protein BNIP3 and cell cycle related proteins Cdk4 and cyclin
      D1. The above results could explain the novel mechanisms of action of the
      combination therapy. We also show here that gemcitabine in combination with P276
      00 is much more effective as an antitumor agent compared with either agent alone
      in the PANC-1 xenograft tumor model in SCID mice. CONCLUSIONS: The
      chemosensitzation of pancreatic tumors to gemcitabine would likely be an
      important and novel strategy for treatment of pancreatic cancer and enable the
      use of lower and safer concentrations, to pave the way for a more effective
      treatment in this devastating disease. Phase IIb clinical trials of P276-00 in
      combination with gemcitabine in pancreatic cancer patients are ongoing.

PMID- 22873290
TI  - Urothelial carcinoma of the upper urinary tract diagnosed via FGFR3 mutation
      detection in urine: a case report.
AB  - BACKGROUND: Upper urinary tract cancer is typically diagnosed with urine cytology
      and imaging techniques. These assays can be limited by sensitivity, specificity,
      or technical issues making some diagnoses difficult. CASE PRESENTATION: A 73-year
      old man presented to the clinic with a right renal pelvis filling defect that was
      detected by a CT-scan performed for unrelated reasons. Urine cytology was
      negative. Cystoscopy, retrograde pyelogram, and partial ureteroscopy were unable
      to visualize the lesion resulting in an indeterminate diagnosis. A subsequent CT
      scan confirmed the renal lesion which appeared to have become larger and was
      consistent with urothelial carcinoma. A urine based genetic assay was used to
      test for the presence of urothelial carcinoma. This assay evaluates the presence
      of mutations in fibroblast growth factor receptor 3 (FGFR3). Mutations in FGFR3
      are known to be associated with urothelial carcinoma and have a positive
      predictive value of 95% when detected in patients with no history of TCC. A
      mutation in exon 10 (Y375C) of FGFR3 was identified. Nephroureterectomy was
      performed and the subsequent pathology confirmed urothelial carcinoma. In
      addition, PCR analysis on isolated tumor tissue indicated the tumor carried the
      same FGFR3 mutation as that of the DNA isolated from urine, consistent with the
      tumor being the origin of the mutant DNA. CONCLUSION: This study indicates that
      the FGFR3 urine assay, which was originally developed to monitor bladder cancer,
      is also a useful tool for diagnosing upper urinary tract cancer in a real-life
      setting.

PMID- 22873223
TI  - Prevention of hepatocellular carcinoma: potential targets, experimental models,
      and clinical challenges.
AB  - Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver
      cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the
      limited therapeutic efficacy in advanced HCC, prevention of HCC development could
      be an effective strategy for improving patient prognosis. However, there is still
      no established therapy to meet the goal. Studies have elucidated a wide variety
      of molecular mechanisms and signaling pathways involved in HCC development.
      Genetically-engineered or chemically-treated experimental models of cirrhosis and
      HCC have been developed and shown their potential value in investigating
      molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In
      this review, we overview potential targets of prevention and currently available
      experimental models, and discuss strategies to translate the findings into
      clinical practice.

PMID- 22873291
TI  - Epidemiological association of Campylobacter jejuni groups with pathogenicity
      associated genetic markers.
AB  - BACKGROUND: Campylobacter jejuni, the most leading cause for bacterial
      gastroenteritis worldwide, shows a high genetic diversity among its isolates.
      Recently, we demonstrated the existence of six C. jejuni-groups by combining MLST
      with six genetic markers. These groups were further characterized by the
      detection of cj1321-cj1326, fucP, cj0178, cj0755/cfrA, ceuE, pldA, cstII, and
      cstIII in order (I.) to show further associations between these different genetic
      markers and MLST CCs. Moreover, different studies were able to associate several
      of these markers: a sialylated lipoologosaccharide (cstII/III(+)), the gamma
      glytamyl-transpeptidase (ggt(+)), and the absence of a certain allele of the
      enterochelin-uptake-binding-protein (ceuE(11168)(-)) with severe
      campylobacteriosis, bloody diarrhea and unpleasant outcome. Additionally more
      than half of human Campylobacter-isolates were assigned to a non-livestock clade
      associated with the absence of cj1321-cj1326. These isolates were considered as
      mere colonizers.From the combination of marker genes, the ratio of human isolates
      in a specific group, and clinical data (II.) it should be demonstrated to which
      of the previous defined groups these Campylobacter-subpopulations, associated
      with higher virulence, correspond. RESULTS: Besides the marker gene pldA, all new
      estimated genetic markers show significant differences in their distribution
      among the various MLST-based groups. Especially the genes for cj1321-cj1326,
      fucP, cj0178, cj0755/cfrA are widely associated with each other and split the
      study population into two major and seven intermediate groups substantiating the
      previous group-definition, whereas cstII and cstIII indicate at least three
      groups following an independent distribution pattern. CONCLUSIONS: Based on these
      data a group of C. jejuni-isolates characterized by the presence of ansB, dmsA,
      ggt, and the absence of cj1365c, cj1585c, cj1321-cj1326, fucP, cj0178,
      cj0755/cfrA, and cstII/III was associated with a higher prevalence in human
      campylobacteriosis, bloody diarrhea as well as hospitalization and bears
      obviously a higher virulence for humans. In contrast to that better livestock
      adapted groups characterized by the ability to utilize L-fucose and the presence
      of all of the five identified putative C. jejuni iron-uptake systems as well as
      cj1321-cj1326, cj1365c, cj1585c, and cstII and/or cstIII (sialylated
      lipoologosaccharide) is more prevalent in animal hosts and was secondary
      associated with less severe campylobacteriosis.

PMID- 22873339
TI  - Two-patch dispersal-linked compensatory-overcompensatory spatially discrete
      population models.
AB  - We study the role of asynchronous and synchronous dispersals on discrete-time two
      patch dispersal-linked population models, where the pre-dispersal local patch
      dynamics are of mixed compensatory and overcompensatory types. Single-species
      dispersal-linked models behave as single-species single-patch models whenever all
      pre-dispersal local patch dynamics are compensatory and dispersal is synchronous.
      However, the dynamics of the corresponding two-patch population model connected
      by asynchronous dispersal depends on the dispersal rates. The species goes
      extinct on at least one patch when the asynchronous dispersal rates are high,
      while it persists when the rates are low. We use numerical simulations to show
      that in both synchronous and asynchronous mixed compensatory and overcompensatory
      systems, symmetric and asymmetric dispersals can control and impede the onset of
      cyclic population oscillations via period-doubling reversal bifurcations. Also,
      we show that in mixed systems both asynchronous and synchronous dispersals are
      capable of altering the pre-dispersal local patch dynamics from overcompensatory
      to compensatory dynamics. Dispersal-linked population models with 'unstructured'
      overcompensatory pre-dispersal local dynamics connected by synchronous dispersal
      can generate multiple attractors with fractal basin boundaries. However, mixed
      compensatory and overcompensatory systems appear to exhibit single attractors and
      not coexisting (multiple) attractors.

PMID- 22873340
TI  - Parametric dependence in model epidemics. I: contact-related parameters.
AB  - One of the interesting properties of nonlinear dynamical systems is that
      arbitrarily small changes in parameter values can induce qualitative changes in
      behavior. The changes are called bifurcations, and they are typically visualized
      by plotting asymptotic dynamics against a parameter. In some cases, the resulting
      bifurcation diagram is unique: irrespective of initial conditions, the same
      dynamical sequence obtains. In other cases, initial conditions do matter, and
      there are coexisting sequences. Here we study an epidemiological model in which
      multiple bifurcation sequences yield to a single sequence in response to varying
      a second parameter. We call this simplification the emergence of unique
      parametric dependence (UPD) and discuss how it relates to the model's overall
      response to parameters. In so doing, we tie together a number of threads that
      have been developing since the mid-1980s. These include period-doubling;
      subharmonic resonance, attractor merging and subduction and the evolution of
      strange invariant sets. The present paper focuses on contact related parameters.
      A follow-up paper, to be published in this journal, will consider the effects of
      non-contact related parameters.

PMID- 22873292
TI  - Physiologic variations of serum tumor markers in gynecological malignancies
      during pregnancy: a systematic review.
AB  - BACKGROUND: Recent insights provide support for the treatment of cancer during
      pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to
      critically review studies on the physiologic variations during pregnancy, the
      most common tumor markers used in diagnosis and follow-up of gynecological
      cancers. METHODS: We conducted a systematic review of six tumor markers during
      normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell
      carcinoma antigen (cervical cancer); and CA 125, anti-Mullerian hormone, inhibin
      B and lactate dehydrogenase (ovarian cancer). RESULTS: For CA 15-3, 3.3% to 20.0%
      of all measurements were above the cut-off (maximum 56 U/mL in the third
      trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and
      10.5% of the measurements (maximum 4.3 ug/L in the third trimester). Up to 35% of
      CA 125 levels were above cut-off: levels were highest in the first trimester,
      with a maximum value up to 550 U/mL. Inhibin B, anti-Mullerian hormone and
      lactate dehydrogenase levels were not elevated in maternal serum during normal
      pregnancy. CONCLUSION: During normal pregnancy, tumor markers including CA 15.3,
      squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti
      Mullerian hormone and lactate dehydrogenase levels remain below normal cut-off
      values. Knowledge of physiological variations during pregnancy can be clinically
      important when managing gynecological cancers in pregnant patients.

PMID- 22873341
TI  - Coexistence of competing juvenile-adult structured populations.
AB  - The Leslie-Gower model is a discrete time analog of the competition Lotka
      Volterra model and is known to possess the same dynamic scenarios of that famous
      model. The Leslie-Gower model played a historically significant role in the
      history of competition theory in its application to classic laboratory
      experiments of two competing species of flour beetles (carried out by Park in the
      1940s-1960s). While these experiments generally supported what became the
      Competitive Exclusion Principle, Park observed an anomalous coexistence case.
      Recent literature has discussed Park's 'coexistence case' by means of non-Lotka
      Volterra, non-equilibrium dynamics that occur in a high dimensional model with
      life cycle stages. We study this dynamic possibility in the lowest possible
      dimension, that is to say, by means of a model involving only two species each
      with two life cycle stages. We do this by extending the Leslie-Gower model so as
      to describe the competitive interaction of two species with juvenile and adult
      classes. We give a complete account of the global dynamics of the resulting model
      and show that it allows for non-equilibrium competitive coexistence as
      competition coefficients are increased. We also show that this phenomenon occurs
      in a general class of models for competing populations structured by juvenile and
      adult life cycle stages.

PMID- 22873343
TI  - Molecular dynamics simulations on aqueous two-phase systems - Single PEG
      molecules in solution.
AB  - BACKGROUND: Molecular Dynamics (MD) simulations are a promising tool to generate
      molecular understanding of processes related to the purification of proteins.
      Polyethylene glycols (PEG) of various length are commonly used in the production
      and purification of proteins. The molecular mechanisms behind PEG driven
      precipitation, aqueous two-phase formation or the effects of PEGylation are
      however still poorly understood. RESULTS: In this paper, we ran MD simulations of
      single PEG molecules of variable length in explicitly simulated water. The
      resulting structures are in good agreement with experimentally determined 3D
      structures of PEG. The increase in surface hydrophobicity of PEG of longer chain
      length could be explained on an atomic scale. PEG-water interactions as well as
      aqueous two-phase formation in the presence of PO4 were found to be correlated to
      PEG surface hydrophobicity. CONCLUSIONS: We were able to show that the taken MD
      simulation approach is capable of generating both structural data as well as
      molecule descriptors in agreement with experimental data. Thus, we are confident
      of having a good in silico representation of PEG.

PMID- 22873342
TI  - Preliminary trial of aloe vera gruel on HIV infection.
AB  - BACKGROUND: Ten (10) young women diagnosed with human immunodeficiency virus
      (HIV) infection in the Wesley Guild Hospital Ilesa, a unit of Obafemi Awolowo
      University Teaching Hospital, Ile Ife, Osun State, Nigeria who did not meet the
      national criteria for the use of antiretroviral drugs were managed with 30-40 mL
      of aloe vera (Aloe barbadensis miller) gruel daily. METHODS: Their CD4 counts,
      general improvement, and physical well-being (including weight gain) were
      monitored over a 1-year period. The findings were compared with those of 20 age-
      matched controls who were on antiretroviral drugs. One (1) patient who reacted
      badly to antiretroviral drug switched over to aloe vera. RESULTS: The average
      weight gain among those on aloe vera was 4.7 kg compared to 4.8 kg by those on
      antiretroviral drug (p=0.916). The average rise in CD4 count among them was 153.7
      cells/MUL compared to 238.85 cells/MUL among the controls (p=0.087). There was no
      significant side effect(s) in either group except in the 1 patient who switched
      over from antiretroviral drugs to aloe vera gruel. CONCLUSIONS: These preliminary
      data suggest that consumption of aloe vera may be of help to HIV-infected
      individuals in the tropics, given its availability and inexpensiveness.

PMID- 22873344
TI  - Quantum mechanical design and structures of hexanuclear sandwich complex and its
      multidecker sandwich clusters (Li6)n([18]annulene)n+1 (n = 1-3).
AB  - By means of density functional theory, a hexanuclear sandwich complex
      [18]annulene-Li6-[18]annulene which consists of a central Li6 hexagon ring and
      large face-capping ligands, [18]annulene, is designed and investigated. The large
      interaction energy and HOMO-LUMO gap suggest that this novel charge-separated
      complex is highly stable and may be experimentally synthesized. In addition, the
      stability found in the [18]annulene-Li6-[18]annulene complex extends to
      multidecker sandwich clusters (Li6)n([18]annulene)n+1 (n = 2-3). The energy gain
      upon addition of a [18]annulene-Li6 unit to (Li6)n-1([18]annulene)n is pretty
      large (96.97-98.22 kcal/mol), indicating that even larger multideckers will also
      be very stable. Similar to ferrocene, such a hexanuclear sandwich complex could
      be considered as a versatile building block to find potential applications in
      different areas of chemistry, such as nanoscience and material science. 

PMID- 22873345
TI  - Covalently linked, water-dispersible, cyclodextrin: reduced-graphene oxide
      sheets.
AB  - Reduced-graphene oxide (rGO) sheets have been functionalized by covalently
      linking beta-cyclodextrin (beta-CD) cavities to the sheets via an amide linkage.
      The functionalized beta-CD:rGO sheets, in contrast to rGO, are dispersible over a
      wide range of pH values (2-13). Zeta potential measurements indicate that there
      is more than one factor responsible for the dispersibility. We show here that
      planar aromatic molecules adsorbed on the rGO sheet as well as nonplanar
      molecules included in the tethered beta-CD cavities have their fluorescence
      effectively quenched by the beta-CD:rGO sheets. The beta-CD:rGO sheets combine
      the hydrophobicity associated with rGO along with the hydrophobicity of the
      cyclodextrin cavities in a single water-dispersible material.

PMID- 22873346
TI  - Advances in monitoring of aspirin therapy.
AB  - The efficacy of aspirin to prevent thrombotic events in cardiovascular patients
      is well established, with >100 randomized trials having been conducted in high
      risk patients and demonstrating a reduction in vascular death of approximately
      15% and a further reduction in non-fatal vascular events of approximately 30%.
      While the benefit of aspirin is undisputed, it is also known that aspirin is
      associated with a dose-dependent increase in the risk of bleeding. It follows
      that most treatment guidelines advocate the use of the lowest aspirin dose
      effective in preventing thrombotic complications to minimize the risk of major
      bleeding. From this, a need for monitoring of aspirin therapy has emerged and
      prompted the development and investigation of numerous assays of platelet
      function. The intention behind monitoring of aspirin's antithrombotic effects is
      to maximize benefit and to personalize treatment based on individual patient
      characteristics. This article reviews the recent literature on the usefulness of
      platelet function testing in patients requiring aspirin; the variability of
      platelet reactivity in patients taking aspirin and its clinical impact; the
      potential mechanisms underlying suboptimal platelet inhibition by aspirin and
      future directions in terms of management of aspirin therapy.

PMID- 22873348
TI  - Synthesis and structural characterization of Na(x)Si136 (0 < x <= 24) single
      crystals and low-temperature transport of polycrystalline specimens.
AB  - Na(x)Si(136) clathrate-II single crystals with x = 2.9, 5.1, 8.2, and 14.7 were
      prepared by a two-step process. In the first step, Na(24)Si(136) single crystals
      were grown from the precursor Na(4)Si(4) by reaction of the vapor phase with
      spatially separated graphite in a closed volume. In the second step, the
      Na(24)Si(136) single crystals were subjected to thermal decomposition in a
      nitrogen atmosphere at 10 Torr and 405  degrees C. The Na content was controlled
      by the duration of thermal decomposition. The structural properties were
      investigated using single-crystal X-ray diffraction and compared with those of
      single-crystal Na(24)Si(136). The quality of the obtained products also allowed
      for low-temperature transport property measurements on agglomerates of crystals
      allowing for an investigation into the low-temperature electrical and thermal
      properties as a function of Na content.

PMID- 22873347
TI  - Redox instability and hemin loss of mutant sperm whale myoglobins induced by 4
      hydroxynonenal in vitro.
AB  - The effects of 4-hydroxy-2-nonenal (HNE) on redox stability of Oxy- and Deoxy-
      wild-type (WT) and recombinant sperm whale myoglobins (P88H/Q152H, L29F, H97A,
      and H64F) and hemin loss from Met-myoglobin (Mb) were investigated. HNE induced
      greater redox instability in WT and mutant Mbs compared to controls (p < 0.05).
      The extent of HNE-induced OxyMb oxidation was lesser in L29F (p < 0.05) and
      greater in H97A and P88H/Q152H than in WT (p < 0.05). H64F DeoxyMb was more redox
      stable than WT DeoxyMb in the presence of HNE (p < 0.05). HNE alkylation occurred
      exclusively on histidine residues, and histidine 48 was alkylated in all sperm
      whale myoglobins. HNE alkylation accelerated the protoporphyrin moiety loss only
      in H97A. Met- forms of WT and L29F but not Deoxy- or Oxy- forms released hemin
      during storage. Primary structure strongly influenced Mb redox stability in the
      presence of reactive secondary lipid oxidation products. 

PMID- 22873349
TI  - Effect of telmisartan on the expression of adiponectin receptors and nicotinamide
      adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic
      rats.
AB  - BACKGROUND: Diabetic cardiovascular disease is associated with decreased
      adiponectin and increased oxidative stress. This study investigated the effect of
      telmisartan on the expression of adiponectin receptor 2 (adipoR2) and
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the heart
      and the expression of adiponectin receptor 1 (adipoR1) in aorta in type 2
      diabetic rats. METHODS: Type 2 diabetes was induced by high-fat and high-sugar
      diet and intraperitoneal injection of a low dose of streptozotocin (STZ). Heart
      function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte
      chemoattractant protein-1(MCP-1) and connective tissue growth factor (CTGF)in the
      heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-kappaB) in aorta were
      analyzed in controls and diabetic rats treated with or without telmisartan
      (5mg/kg/d) by gavage for 12 weeks. RESULTS: Heart function, plasma and myocardial
      adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were
      significantly decreased in diabetic rats (P <0.05). The expression of myocardial
      p22phox, NOX4, MCP-1, and CTGF was significantly increased in diabetic rats (P
      <0.05). The expression of adipoR1 was decreased and the expression of MCP-1 and
      NF-kappaB was increased in the abdominal aorta in diabetic rats (P <0.05).
      Telmisartan treatment significantly attenuated these changes in diabetic rats (P
      <0.05). CONCLUSIONS: Our results suggest that telmisartan upregulates the
      expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously,
      it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF,
      contributing so to the improvement of heart function in diabetic rats.
      Telmisartan also induces a protective role on the vascular system by upregulating
      the expression of adipoR1 and downregulating the expression of MCP-1 and NF
      kappaB in the abdominal aorta in diabetic rats.

PMID- 22873350
TI  - Preeclampsia: a bioinformatics approach through protein-protein interaction
      networks analysis.
AB  - BACKGROUND: In this study we explored preeclampsia through a bioinformatics
      approach. We create a comprehensive genes/proteins dataset by the analysis of
      both public proteomic data and text mining of public scientific literature. From
      this dataset the associated protein-protein interaction network has been
      obtained. Several indexes of centrality have been explored for hubs detection as
      well as the enrichment statistical analysis of metabolic pathway and disease.
      RESULTS: We confirmed the well known relationship between preeclampsia and
      cardiovascular diseases but also identified statistically significant
      relationships with respect to cancer and aging. Moreover, significant metabolic
      pathways such as apoptosis, cancer and cytokine-cytokine receptor interaction
      have also been identified by enrichment analysis. We obtained FLT1, VEGFA, FN1,
      F2 and PGF genes with the highest scores by hubs analysis; however, we also found
      other genes as PDIA3, LYN, SH2B2 and NDRG1 with high scores. CONCLUSIONS: The
      applied methodology not only led to the identification of well known genes
      related to preeclampsia but also to propose new candidates poorly explored or
      completely unknown in the pathogenesis of preeclampsia, which eventually need to
      be validated experimentally. Moreover, new possible connections were detected
      between preeclampsia and other diseases that could open new areas of research.
      More must be done in this area to resolve the identification of unknown
      interactions of proteins/genes and also for a better integration of metabolic
      pathways and diseases.

PMID- 22873351
TI  - Women with gestational diabetes in Vietnam: a qualitative study to determine
      attitudes and health behaviours.
AB  - BACKGROUND: Diabetes is increasing in prevalence globally, notably amongst
      populations from low- and middle- income countries. Gestational Diabetes
      Mellitus(GDM), a precursor for type 2 diabetes, is increasing in line with this
      trend. Few studies have considered the personal and social effects of GDM on
      women living in low and middle-income countries. The aim of this study was
      determine attitudes and health behaviours of pregnant women with GDM in Vietnam.
      METHODS: This was a qualitative study using focus group methodology conducted in
      Ho Chi Minh City. Pregnant women, aged over 18 years, with GDM were eligible to
      participate. Women were purposely sampled to obtain a range of gestational ages
      and severity of disease. They were invited to attend a 1-hour focus group.
      Questions were semi structured around six themes. Focus groups were recorded,
      transcribed, translated and cross-referenced. Non-verbal and group interactions
      were recorded. Thematic analysis was performed using a theoretical framework
      approach. RESULTS: From December 2010 to February 2011, four focus groups were
      conducted involving 34 women. Median age was 31.5 years (range 23 to 44), median
      BMI 21.8 kg/m(2). Women felt confusion, anxiety and guilt about GDM. Many
      perceived their baby to be at increased risk of death. Advice to reduce dietary
      starch was confusing. Women reported being 'hungry' or 'starving' most of the
      time, unaware of appropriate food substitutions. They were concerned about
      transmission of GDM through breast milk. Several women planned not to breastfeed.
      All felt they needed more information. Current sources of information included
      friends, magazines, a health phone line or the Internet. Women felt small group
      sessions and information leaflets could benefit them. CONCLUSIONS: This study
      highlights the need for culturally appropriate clinical education and health
      promotion activities for women with GDM in Vietnam.

PMID- 22873353
TI  - Climate change, climate variability and brucellosis.
AB  - In addition to natural climate variability observed over comparable time periods,
      climate change is attributed directly or indirectly to human activity, altering
      the composition of global atmosphere. This phenomenon continues to be a
      significant and global threat for the humankind, and its impact compromises many
      aspects of the society at different levels, including health. The impact of
      climate change on zoonotic diseases has been largely ignored, particularly
      brucellosis. We here review some direct and indirect evidences of the impact of
      climate change and climate variability on brucellosis.

PMID- 22873352
TI  - Clinical presentations and diagnosis of brucellosis.
AB  - Brucellosis is a worldwide zoonosis caused by Brucella species. The disease
      remains a significant economic and public health problem particularly in the
      Mediterranean countries. Clinical manifestations of brucellosis are variable and
      often nonspecific, simulating infectious and noninfectious diseases.
      Osteoarticular involvement is the most common focal complication of brucellosis
      and morbidity. Mortality rate due to brucellosis is low, mostly secondary to
      endocarditis and central nerve involvement of disease. The diagnosis of
      brucellosis depends on the clinical presentations and laboratory tests. Detection
      of Brucella species by culture method is sometimes unsuccessful; therefore,
      serological tests are preferred. These tests are easy to perform, and results can
      be obtained within a short span of time. Several serologic tests have been
      developed for the diagnosis of human brucellosis, including the standard
      agglutination tube (SAT) test, anti-human globulin (Coombs) test, indirect
      fluorescence antibody (IFA) test, and enzyme-linked immunosorbent assay (ELISA).
      SAT is the primary test used in many clinical laboratories. IFA and ELISA are
      simple and reliable for the detection of immunoglobulin classes especially in
      complicated cases. Polymerase chain reaction (PCR) technique is highly sensitive
      and specific for the determination of Brucella spp. from peripheral blood and
      other tissues. Recent patents are especially based on molecular assays in the
      diagnosis of brucellosis. However, PCR is still expensive and may not be
      appropriate for daily practice.

PMID- 22873354
TI  - Ru(II)-catalyzed amidation of 2-arylpyridines with isocyanates via C-H
      activation.
AB  - An efficient Ru(II)-catalyzed amidation of 2-arylpyridines with isocyanates via C
      H bond activation is described.

PMID- 22873356
TI  - Effect of antenatal tocolysis on neonatal outcomes.
AB  - OBJECTIVE: Detail adverse neonatal effects in pregnancies treated with
      indomethacin (I), magnesium sulfate (M) or nifedipine (N). METHODS: Women in
      acute preterm labor with cervical dilatation 1-6 cm were randomized to receive
      one of three first-line tocolytic drugs. RESULTS: There were 317 neonates (I =
      103, M = 95, N = 119) whose mothers were treated with tocolytic therapy. There
      was no difference in gestational age at randomization (average 28.6 weeks'
      gestation) or at delivery (31.6 weeks' gestation, p = 0.551), birth weight (p =
      0.871) or ventilator days (p = 0.089) between the three groups. Neonatal
      morbidity was not different between the three groups; respiratory distress
      syndrome (p = 0.086), patent ductus arteriosus (p = 0.592), sepsis (p = 0.590),
      necrotizing enterocolitis (p = 0.770), intraventricular hemorrhage (p = 0.669)
      and periventricular leukomalacia (p = 0.124). CONCLUSIONS: There were no
      statistically significant differences between the three tocolytics as far as
      composite neonatal morbidity or mortality was concerned.

PMID- 22873355
TI  - Podosomes in migrating microglia: components and matrix degradation.
AB  - BACKGROUND: To perform their functions during development and after central
      nervous system injury, the brain's immune cells (microglia) must migrate through
      dense neuropil and extracellular matrix (ECM), but it is not known how they
      degrade the ECM. In several cancer cell lines and peripheral cells, small multi
      molecular complexes (invadopodia in cancer cells, podosomes in nontumor cells)
      can both adhere to and dissolve the ECM. Podosomes are tiny multi-molecular
      structures (0.4 to 1 MUm) with a core, rich in F-actin and its regulatory
      molecules, surrounded by a ring containing adhesion and structural proteins.
      METHODS: Using rat microglia, we performed several functional assays: live cell
      imaging for chemokinesis, degradation of the ECM component, fibronectin, and
      chemotactic invasion through MatrigelTM, a basement membrane type of ECM.
      Fluorescent markers were used with high-resolution microscopy to identify
      podosomes and their components. RESULTS: The fan-shaped lamella at the leading
      edge of migrating microglia contained a large F-actin-rich superstructure
      composed of many tiny (<1 MUm) punctae that were adjacent to the substrate, as
      expected for cell-matrix contact points. This superstructure (which we call a
      podonut) was restricted to cells with lamellae, and conversely almost every
      lamella contained a podonut. Each podonut comprised hundreds of podosomes, which
      could also be seen individually adjacent to the podonut. Microglial podosomes
      contained hallmark components of these structures previously seen in several cell
      types: the plaque protein talin in the ring, and F-actin and actin-related
      protein (Arp) 2 in the core. In microglia, podosomes were also enriched in
      phosphotyrosine residues and three tyrosine-kinase-regulated proteins: tyrosine
      kinase substrate with five Src homology 3 domains (Tks5), phosphorylated caveolin
      1, and Nox1 (nicotinamide adenine dinucleotide phosphate oxidase 1). When
      microglia expressed podonuts, they were able to degrade the ECM components,
      fibronectin, and MatrigelTM. CONCLUSION: The discovery of functional podosomes in
      microglia has broad implications, because migration of these innate immune cells
      is crucial in the developing brain, after damage, and in disease states involving
      inflammation and matrix remodeling. Based on the roles of invadosomes in
      peripheral tissues, we propose that microglia use these complex structures to
      adhere to and degrade the ECM for efficient migration.

PMID- 22873357
TI  - Assessment of the level of asthma control among adult patients in two tertiary
      care centers in Nigeria.
AB  - BACKGROUND: According to the Global Initiative for Asthma (GINA) guidelines, the
      goal of asthma management is to achieve clinical control. Uncontrolled asthma
      places a significant social and economic burden on patients. OBJECTIVE: The two
      aims of this study were to (1) assess the level of asthma control (according to
      the GINA definition of "control") among adult patients attending two tertiary
      care centers in Nigeria and (2) to determine the predictors associated with
      uncontrolled asthma. METHODS: This cross-sectional study was carried out from
      June 2009 to December 2010. The participants were all 18 years old or older with
      physician-diagnosed asthma. First, the participants completed an interviewer
      administered questionnaire, which included items that collected their socio
      demographic information and clinical data. Second, anthropometric indices were
      measured and spirometry was conducted to determine each participant's lung
      function. Finally, the researcher team members assessed each participant's
      inhaler device technique. The outcome measures were (1) uncontrolled asthma, (2)
      partly controlled asthma, and (3) controlled asthma. RESULTS: One hundred and
      twenty-four asthma patients participated in the study. Of these, 69.3% had
      uncontrolled asthma, 22.6% had partly controlled asthma, and 8.1% had controlled
      asthma. Multivariate analysis showed that uncontrolled asthma was strongly
      associated with asthma severity based on clinical features, the incorrect use of
      an inhaler device, the use of oral corticosteroids, an abnormal pulmonary
      function test, the presence of comorbidity, and the lack of adherence to inhaled
      corticosteroids (ICSs). The results also revealed that increasing age and a lack
      of tertiary education were weakly associated with asthma control. In this study,
      gender, marriage, smoking status, occupation, socioeconomic status, income, and
      the duration of the asthma were not associated with asthma control. CONCLUSION: A
      significant proportion of the sampled patients had uncontrolled asthma. To reduce
      this number, health care providers must reinforce the education of each asthma
      patient and promote the regular assessment of asthma control at every clinic
      visit, identify those with poor control, and institute the appropriate therapy
      needed to achieve clinical control.

PMID- 22873358
TI  - Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with
      patient survival and clinical response.
AB  - BACKGROUND: This study was performed to determine if a chemotherapy-induced
      apoptosis assay (MiCK) could predict the best therapy for patients with ovarian
      cancer. METHODS: A prospective, multi-institutional and blinded trial of the
      assay was conducted in 104 evaluable ovarian cancer patients treated with
      chemotherapy. The MiCK assay was performed prior to therapy, but treating
      physicians were not told of the results and selected treatment only on clinical
      criteria. Outcomes (response, time to relapse, and survival) were compared to the
      drug-induced apoptosis observed in the assay. RESULTS: Overall survival in
      primary therapy, chemotherapy naive patients with Stage III or IV disease was
      longer if patients received a chemotherapy which was best in the MiCK assay,
      compared to shorter survival in patients who received a chemotherapy that was not
      the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed
      use of the best chemotherapy in the MiCK assay was the strongest predictor of
      overall survival (p < 0.01) in stage III or IV patients. Standard therapy with
      carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK
      assay in 44% of patients. If patients received C + P and it was the best
      chemotherapy in the MiCK assay, they had longer survival than those patients
      receiving C + P when it was not the best chemotherapy in the assay (p = 0.03).
      Relapse-free interval in primary therapy patients was longer if patients received
      the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR
      + PR) were higher if physicians used an active chemotherapy based on the MiCK
      assay (p = 0.03). CONCLUSION: The MiCK assay can predict the chemotherapy
      associated with better outcomes in ovarian cancer patients. This study quantifies
      outcome benefits on which a prospective randomized trial can be developed.

PMID- 22873359
TI  - Affective modulation of the startle reflex following traumatic brain injury.
AB  - Diminished emotional recognition, expression, and responsivity are frequent
      legacies of traumatic brain injury (TBI) that can have an adverse impact on
      relationships and psychosocial recovery. However, assessment of emotion
      responsivity is often difficult because many patients lack insight into their
      altered personality. To overcome this obstacle, we used a physiological measure
      of emotion responsivity, the startle reflex, to examine how this can vary
      according to the affective valence of stimuli by comparing a TBI group with a
      matched control group. The study also examined whether weaknesses of attention
      and speed of information processing could account for differences in startle
      modulation across groups. Sixty-four TBI patients and controls completed the
      startle reflex procedure. Participants were presented with pictures that differed
      in affective valence, and measures were taken of eyeblink startle responses to an
      acoustic probe. Subjective ratings of affect and arousal for each picture were
      obtained, and TBI patients completed measures of attention and information
      processing. Results revealed that the TBI group did not show the pattern of
      startle modulation observed in the control group. Whilst pleasant pictures
      produced the usual attenuation of the startle response, startle responses to
      unpleasant pictures were significantly lower in the TBI group than in controls.
      No significant correlations emerged between startle responses and performance on
      neuropsychological measures in the TBI group. The TBI group also rated unpleasant
      pictures as significantly less arousing than did controls. The results provide
      partial support for a growing body of evidence that has proposed impaired emotion
      responsivity following TBI.

PMID- 22873360
TI  - Native intra- and inter-specific reactions may cause the paradox of pest control
      with harvesting.
AB  - We analyse a general time-discrete mathematical model of host-parasite population
      dynamics with harvesting, in which the host can be regarded as a pest. We harvest
      a portion of the host population at a moment in each year. Our model involves the
      density effect on the host population. We investigate the condition in which the
      harvesting of the host results in a paradoxical increase of its equilibrium
      population size. Our results imply that for a family of pest-enemy systems, the
      paradox of pest control could be caused essentially by the interspecific
      relationship and the intraspecific density effect.

PMID- 22873361
TI  - Mathematical modelling and experiments for the proliferation and differentiation
      of Drosophila intestinal stem cells I.
AB  - We study the proliferation and differentiation of stem cells in the Drosophila
      posterior midgut epithelium, which mainly consists of intestinal stem cells
      (ISCs); semi-differentiated cells, i.e. enteroblasts (EBs); and two types of
      fully differentiated cells, i.e. enteroendocrine cells (EEs) and enterocytes
      (ECs). The cellular system of ISCs is controlled by Wnt and Notch signalling
      pathways. In this article, we experimentally show that EBs are not capable of
      efficiently differentiating into ECs in the absence of Wnt signalling. On the
      basis of the experimental results and known facts, we propose a scheme and a
      simple ordinary differential equation (ODE) model for the proliferation and
      differentiation of ISCs. This is a first step towards understanding the universal
      mechanism for the maintenance of the cellular system of tissue stem cells
      controlled by signalling pathways.

PMID- 22873362
TI  - Global stability of pathogen-immune dynamics with absorption.
AB  - In this paper, we consider the global stability of the models which incorporate
      humoural immunity or cell-mediated immunity. We consider the effect of loss of a
      pathogen, which is called the absorption effect when it infects an uninfected
      cells. We construct Lyapunov functions for these models under some conditions of
      parameters, and prove the global stability of the interior equilibria. It is
      impossible to remove the condition of parameters for the model incorporating
      humoural immunity.

PMID- 22873363
TI  - On the optimal duration of memory of losing a conflict--a mathematical model
      approach.
AB  - In male broad-horned flour beetles, Gnatocerus cornutus, losers of conflicts
      avoid fighting at subsequent encounters. The loser effect lasts for 4 days. It is
      considered that the memory of losing remains for 4 days. The duration of the
      memory is expected to affect the fitness, and the duration, 4 days, is expected
      to be optimal. We consider the fitness of a mutant in an homogeneous population
      to obtain the optimal duration. Here we carry out simulations using an individual
      based model. The results suggest that the trade-off of getting mating chances and
      avoiding damage can cause the optimal duration of the memory, and that the decay
      in time of the female population is an important factor.

PMID- 22873364
TI  - Global stability of models of humoral immunity against multiple viral strains.
AB  - We analyse, from a mathematical point of view, the global stability of equilibria
      for models describing the interaction between infectious agents and humoral
      immunity. We consider the models that contain the variables of pathogens
      explicitly. The first model considers the situation where only a single strain
      exists. For the single strain model, the disease steady state is globally
      asymptotically stable if the basic reproductive ratio is greater than one. The
      other models consider the situations where multiple strains exist. For the multi
      strain models, the disease steady state is globally asymptotically stable. In the
      model that does not explicitly contain an immune variable, only one strain with
      the maximum basic reproductive ratio can survive at the steady state. However, in
      our models explicitly involving the immune system, multiple strains coexist at
      the steady state.

PMID- 22873365
TI  - A discrete model of avian influenza with seasonal reproduction and transmission.
AB  - In this paper, we formulate a discrete-time model with the reproductive and
      overwintering periods to assess the impact of avian influenza transmission in
      poultry. It is shown that the disease is extinct if the basic reproduction number
      is less than one and is persistent if the basic reproductive number is greater
      than one. Furthermore, the model admits a closed invariant cycle, which means
      that avian influenza fluctuates in poultry.

PMID- 22873366
TI  - Regioselective oxazolination of C70(2-) and formation of cis-1 C70 adduct with
      respect to the apical pentagon.
AB  - Oxazolination of C(70) has been achieved via the aerobic oxidation of C(70)(2-)
      in the presence of PhCN. Only one C(70) oxazoline regioisomer (1) is obtained,
      indicating that the oxazolination of C(70)(2-) occurs with an unusual
      regioselectivity. Further benzylation of 1(2-) with benzyl bromide leads to the
      formation of the first cis-1 C(70) derivative with respect to the apical pentagon
      (2), as shown by the X-ray single-crystal structure and various spectral
      characterizations. The structure of the obtained C(70) oxazoline (1) is resolved
      with H/D labeling benzylation and HMBC (heteronuclear multiple bond coherence)
      NMR on the basis of the structure of 2. The result shows that for compound 1, the
      O atom is selectively bonded to the C1, while the N atom is bonded to the C2 of
      C(70). The exhibited regioselectivity for the orientation of oxazolino group on
      C(70) is further rationalized with computational calculations, and a reaction
      mechanism for the oxazolination of C(70)(2-) is proposed.

PMID- 22873368
TI  - mTor as a potential target for the prevention and treatment of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a global health problem and responsible for up
      to 500.000 deaths annually. It usually occurs secondary to infections with
      hepatitis B or C viruses, alcohol consumption, non-alcoholic steatohepatitis or
      hereditary liver diseases. The prognosis for patients with advanced disease is
      dismal; therefore, new strategies to prevent or treat this malignancy are
      urgently needed. Over recent years, several molecular pathways have been
      identified contributing to the molecular pathogenesis of this devastating
      disease, among them the PI3K/AKT/mTOR pathway. mTOR is effectively inhibited by
      rapamycin and its derivatives such as temsirolimus and everolimus. The anti-tumor
      activity of rapamycin was identified more than 30 years ago in a screen performed
      at the National Cancer Institute, but was subsequently not developed for cancer
      treatment. In the 1990s, activation of the mTOR pathway was recognized in various
      malignancies spurring again the interest in mTOR inhibitors for anti-cancer
      treatment. In 2007, the US Food and Drug Administration approved the first mTOR
      inhibitor, temsirolimus, for the treatment of renal cell carcinoma. Currently,
      several clinical studies are underway to define the role of mTOR inhibitors for
      the treatment of hepatocellular carcinoma. The aim of this review is to outline
      the role of mTOR for hepatocarcinogenesis. We will also discuss the latest
      preclinical and clinical data of mTOR inhibitors for the prevention and treatment
      of HCC.

PMID- 22873367
TI  - The inSIGHT study: costs and effects of routine hysteroscopy prior to a first IVF
      treatment cycle. A randomised controlled trial.
AB  - BACKGROUND: In in vitro fertilization (IVF) and intracytoplasmatic sperm
      injection (ICSI) treatment a large drop is present between embryo transfer and
      occurrence of pregnancy. The implantation rate per embryo transferred is only
      30%. Studies have shown that minor intrauterine abnormalities can be found in 11
      45% of infertile women with a normal transvaginal sonography or
      hysterosalpingography. Two randomised controlled trials have indicated that
      detection and treatment of these abnormalities by office hysteroscopy after two
      failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore,
      screening of all infertile women for intracavitary pathology prior to the start
      of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such
      a policy, this study will assess the effects and costs of screening for and
      treatment of unsuspected intrauterine abnormalities by routine office
      hysteroscopy, with or without saline infusion sonography (SIS), prior to a first
      IVF/ICSI cycle. METHODS/DESIGN: Multicenter randomised controlled trial in
      asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle,
      with normal findings at transvaginal sonography. Women with recurrent
      miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not
      be included. Participants will be randomised for a routine fertility work-up with
      additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined
      intrauterine abnormalities versus the regular fertility work-up without
      additional diagnostic tests. The primary study outcome is the cumulative ongoing
      pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI
      treatment after randomisation. Secondary study outcome parameters are the
      cumulative implantation rate; cumulative miscarriage rate; patient preference and
      patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed
      according to the intention-to-treat principle, using univariate and multivariate
      logistic regression and cox regression. Cost-effectiveness analysis will be
      performed to evaluate the costs of the additional tests as routine procedure. In
      total 700 patients will be included in this study. DISCUSSION: The results of
      this study will help to clarify the significance of hysteroscopy prior to IVF
      treatment. TRIAL REGISTRATION: NCT01242852.

PMID- 22873369
TI  - The reversible opening of water channels in cytochrome c modulates the heme iron
      reduction potential.
AB  - Dynamic protein-solvent interactions are fundamental for life processes, but
      their investigation is still experimentally very demanding. Molecular dynamics
      simulations up to hundreds of nanoseconds can bring to light unexpected events
      even for extensively studied biomolecules. This paper reports a combined
      computational/experimental approach that reveals the reversible opening of two
      distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c.
      Both channels allow water access to the heme center. By means of a mixed quantum
      mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix
      method (PMM), that allows to reach long simulation times, changes in the
      reduction potential of the heme Fe(3+)/Fe(2+) couple induced by the opening of
      each cavity are calculated. Shifts of the reduction potential upon changes in the
      hydration of the heme propionates are observed. These variations are relatively
      small but significant and could therefore represent a tool developed by
      cytochrome c for the solvent driven, fine-tuning of its redox functionality.

PMID- 22873370
TI  - Four new triterpenes from the endemic relict shrub Tetraena mongolica.
AB  - A chemical investigation of the endemic relict shrub Tetraena mongolica led to
      the isolation of four new triterpenes: 11alpha,12alpha:13beta,28-diepoxyoleanane
      3beta-yl trans-caffeate (1), 3beta-hydroxy-11alpha,12alpha-epoxyoleanane-28-al
      (2), olean-11-en-28-al-3beta-yl trans-caffeate (3), and 28-acetoxy-olean-12-en
      3beta-yl trans-caffeate (4). Their structures were elucidated by extensive
      spectroscopic methods.

PMID- 22873400
TI  - HIV/AIDS-associated opportunistic protozoal diarrhea.
AB  - Human immunodeficiency virus (HIV) infection has altered both the epidemiology
      and outcome of enteric opportunistic parasitic infections. This study was done to
      determine the prevalence and species/genotypes of intestinal coccidian and
      microsporidial infections among HIV/AIDS patients with diarrhea and/or a history
      of diarrhea alternately with an asymptomatic interval, and their association with
      CD4 T cell count. This cross-sectional study was done from May 2010 to May 2011
      in Shiraz University of Medical Sciences, South of Iran. A blood sample was
      obtained from HIV-positive patients for a CD4 T cell count upon enrollment.
      Sociodemographic data and a history of diarrhea were collected by interviewing
      356 consecutive participants (273 males and 83 females). Whenever possible more
      than a fecal sample was collected from all the participants and examined for
      parasites using direct, physiological saline solution ethyl acetate, an acid-fast
      trichrome stain, nested polymerase chain reaction, and sequencing techniques for
      the detection, confirmation, and genotyping of Cryptosporidium spp., Cyclospora
      cayetanensis, Isospora belli, and intestinal microsporidia (Enterocytozoon
      bieneusi). The most common opportunistic and nonopportunistic pathogens were
      Cryptosporidium spp. (C. parvum and C. andersoni), E. bieneusi, Giardia lamblia,
      Sarcocystis spp., and Blastocystis homonis affecting 34, 8, 23, 1, and 14
      patients, respectively. C. cayetanensis, I. belli, Enterobius vermicularis, and
      Hymenolepis nana were observed in few patients. A CD4 count <200 cells/MUl was
      significantly associated with the presence of opportunistic parasites and
      diarrhea (p<0.05). Opportunistic intestinal parasites should be suspected in any
      HIV/AIDS patient with chronic diarrhea. Tropical epidemic nonopportunistic
      enteric parasitic infections among such patients should not be neglected in Iran.

PMID- 22873401
TI  - Structural/functional analysis of the human OXR1 protein: identification of exon
      8 as the anti-oxidant encoding function.
AB  - BACKGROUND: The human OXR1 gene belongs to a class of genes with conserved
      functions that protect cells from reactive oxygen species (ROS). The gene was
      found using a screen of a human cDNA library by its ability to suppress the
      spontaneous mutator phenotype of an E. coli mutH nth strain. The function of OXR1
      is unknown. The human and yeast genes are induced by oxidative stress and
      targeted to the mitochondria; the yeast gene is required for resistance to
      hydrogen peroxide. Multiple spliced isoforms are expressed in a variety of human
      tissues, including brain. RESULTS: In this report, we use a papillation assay
      that measures spontaneous mutagenesis of an E. coli mutM mutY strain, a host
      defective for oxidative DNA repair. Papillation frequencies with this strain are
      dependent upon a G->T transversion in the lacZ gene (a mutation known to occur as
      a result of oxidative damage) and are suppressed by in vivo expression of human
      OXR1. N-terminal, C-terminal and internal deletions of the OXR1 gene were
      constructed and tested for suppression of the mutagenic phenotype of the mutM
      mutY strain. We find that the TLDc domain, encoded by the final four exons of the
      OXR1 gene, is not required for papillation suppression in E. coli. Instead, we
      show that the protein segment encoded by exon 8 of OXR1 is responsible for the
      suppression of oxidative damage in E. coli. CONCLUSION: The protein segment
      encoded by OXR1 exon 8 plays an important role in the anti-oxidative function of
      the human OXR1 protein. This result suggests that the TLDc domain, found in OXR1
      exons 12-16 and common in many proteins with nuclear function, has an alternate
      (undefined) role other than oxidative repair.

PMID- 22873402
TI  - Differential effects of arousal in positive and  negative autobiographical
      memories.
AB  - Autobiographical memories are characterised by a range of emotions and emotional
      reactions. Recent research has demonstrated that differences in emotional valence
      (positive vs. negative emotion) and arousal (the degree of emotional intensity)
      differentially influence the retrieved memory narrative. Although the mnemonic
      effects of valence and arousal have both been heavily studied, it is currently
      unclear whether the effects of emotional arousal are equivalent for positive and
      negative autobiographical events. In the current study, multilevel models were
      used to examine differential effects of emotional valence and arousal on the
      richness of autobiographical memory retrieval both between and within subjects.
      Thirty-four young adults were asked to retrieve personal autobiographical
      memories associated with popular musical cues and to rate the valence, arousal
      and richness of these events. The multilevel analyses identified independent
      influences of valence and intensity upon retrieval characteristics at the within-
      and between-subject levels. In addition, the within-subject interactions between
      valence and arousal highlighted differential effects of arousal for positive and
      negative memories. These findings have important implications for future studies
      of emotion and memory, highlighting the importance of considering both valence
      and arousal when examining the role emotion plays in the richness of memory
      representation.

PMID- 22873403
TI  - Film formation of nonionic dendritic amphiphiles at the water surface.
AB  - This study focuses on the modular synthesis of a new class of nonionic dendritic
      amphiphiles and their behavior at the water-air interface. Our approach is based
      on a modular architecture consisting of two different generations of hydrophilic
      polyol dendrons connected to a two-chain hydrophobic block. Caused by different
      polarities of polyol and aliphatic groups, the molecules are surface-active and,
      by analogy to phospholipids, can form well-organized Langmuir monolayers at the
      water surface. The self-association process and phase behavior of these molecules
      with two different headgroup sizes were investigated by means of surface pressure
      and surface potential area isotherms by surface shear rheology and Brewster angle
      microscopy. With these techniques, we were able to observe marked differences in
      the phase behavior of the two molecular generations.

PMID- 22873404
TI  - Positive surface charge enhances selective cellular uptake and anticancer
      efficacy of selenium nanoparticles.
AB  - Surface charge plays a key role in cellular uptake and biological actions of
      nanomaterials. Selenium nanoparticles (SeNPs) are novel Se species with potent
      anticancer activity and low toxicity. This study constructed positively charged
      SeNPs by chitosan surface decoration to achieve selective cellular uptake and
      enhanced anticancer efficacy. The results of structure characterization revealed
      that hydroxyl groups in chitosan reacted with SeO(3)(2-) ion to form special
      chain-shaped intermediates, which could be decomposed to form crystals upon
      reduction by ascorbic acid. The initial colloids nucleated and then assembled
      into spherical SeNPs. The positive charge of the NH(3)(+) group on the outer
      surface of the nanoparticles contributed to the high stability in aqueous
      solutions. Moreover, a panel of four human cancer cell lines were found to be
      susceptible to SeNPs, with IC(50) values ranging from 22.7 to 49.3 MUM. Chitosan
      surface decoration of SeNPs significantly enhanced the selective uptake by
      endocytosis in cancer cells and thus amplified the anticancer efficacy. Treatment
      of the A375 melanoma cells with chitosan-SeNPs led to dose-dependent apoptosis,
      as evidenced by DNA fragmentation and phosphatidylserine translocation. Our
      results suggest that the use of positively charged chitosan as a surface
      decorator could be a simple and attractive approach to achieve selective uptake
      and anticancer action of nanomaterials in cancer cells.

PMID- 22873405
TI  - Physiological response of Pichia pastoris GS115 to methanol-induced high level
      production of the Hepatitis B surface antigen: catabolic adaptation, stress
      responses, and autophagic processes.
AB  - BACKGROUND: Pichia pastoris is an established eukaryotic host for the production
      of recombinant proteins. Most often, protein production is under the control of
      the strong methanol-inducible aox1 promoter. However, detailed information about
      the physiological alterations in P. pastoris accompanying the shift from growth
      on glycerol to methanol-induced protein production under industrial relevant
      conditions is missing. Here, we provide an analysis of the physiological response
      of P. pastoris GS115 to methanol-induced high-level production of the Hepatitis B
      virus surface antigen (HBsAg). High product titers and the retention of the
      protein in the endoplasmic reticulum (ER) are supposedly of major impact on the
      host physiology. For a more detailed understanding of the cellular response to
      methanol-induced HBsAg production, the time-dependent changes in the yeast
      proteome and ultrastructural cell morphology were analyzed during the production
      process. RESULTS: The shift from growth on glycerol to growth and HBsAg
      production on methanol was accompanied by a drastic change in the yeast proteome.
      In particular, enzymes from the methanol dissimilation pathway started to
      dominate the proteome while enzymes from the methanol assimilation pathway, e.g.
      the transketolase DAS1, increased only moderately. The majority of methanol was
      metabolized via the energy generating dissimilatory pathway leading to a
      corresponding increase in mitochondrial size and numbers. The methanol-metabolism
      related generation of reactive oxygen species induced a pronounced oxidative
      stress response (e.g. strong increase of the peroxiredoxin PMP20). Moreover, the
      accumulation of HBsAg in the ER resulted in the induction of the unfolded protein
      response (e.g. strong increase of the ER-resident disulfide isomerase, PDI) and
      the ER associated degradation (ERAD) pathway (e.g. increase of two cytosolic
      chaperones and members of the AAA ATPase superfamily) indicating that potential
      degradation of HBsAg could proceed via the ERAD pathway and through the
      proteasome. However, the amount of HBsAg did not show any significant decline
      during the cultivation revealing its general protection from proteolytic
      degradation. During the methanol fed-batch phase, induction of vacuolar proteases
      (e.g. strong increase of APR1) and constitutive autophagic processes were
      observed. Vacuolar enclosures were mainly found around peroxisomes and not close
      to HBsAg deposits and, thus, were most likely provoked by peroxisomal components
      damaged by reactive oxygen species generated by methanol oxidation. CONCLUSIONS:
      In the methanol fed-batch phase P. pastoris is exposed to dual stress; stress
      resulting from methanol degradation and stress resulting from the production of
      the recombinant protein leading to the induction of oxidative stress and unfolded
      protein response pathways, respectively. Finally, the modest increase of methanol
      assimilatory enzymes compared to the strong increase of methanol dissimilatory
      enzymes suggests here a potential to increase methanol incorporation into
      biomass/product through metabolic enhancement of the methanol assimilatory
      pathway.

PMID- 22873407
TI  - An efficient organocatalytic method for highly enantioselective Michael addition
      of malonates to enones catalyzed by readily accessible primary amine-thiourea.
AB  - A practical and highly enantioselective Michael addition of malonates to enones
      catalyzed by simple and readily available bifunctional primary amine-thiourea
      derived from 1,2-diaminocyclohexane is reported. The addition of weak acids and
      elevated temperature (ca. 50  degrees C) improved the efficiency of the Michael
      reaction. This approach enables the efficient synthesis of 1,5-ketoesters with
      good yields, excellent enantioselectivities (up to 99% ee), and low loading (0.5
      5 mol %) of simple chiral primary amine-thiourea catalysts, and is applicable in
      multigram scale synthesis.

PMID- 22873406
TI  - Core--strategy leading to high reversible hydrogen storage capacity for NaBH4.
AB  - Owing to its high storage capacity (10.8 mass %), sodium borohydride (NaBH(4)) is
      a promising hydrogen storage material. However, the temperature for hydrogen
      release is high (>500  degrees C), and reversibility of the release is
      unachievable under reasonable conditions. Herein, we demonstrate the potential of
      a novel strategy leading to high and stable hydrogen absorption/desorption
      cycling for NaBH(4) under mild pressure conditions (4 MPa). By an antisolvent
      precipitation method, the size of NaBH(4) particles was restricted to a few
      nanometers (<30 nm), resulting in a decrease of the melting point and an initial
      release of hydrogen at 400  degrees C. Further encapsulation of these
      nanoparticles upon reaction of nickel chloride at their surface allowed the
      synthesis of a core--shell nanostructure, NaBH(4)@Ni, and this provided a route
      for (a) the effective nanoconfinement of the melted NaBH(4) core and its
      dehydrogenation products, and (b) reversibility and fast kinetics owing to short
      diffusion lengths, the unstable nature of nickel borohydride, and possible
      modification of reaction paths. Hence at 350  degrees C, a reversible and steady
      hydrogen capacity of 5 mass % was achieved for NaBH(4)@Ni; 80% of the hydrogen
      could be desorbed or absorbed in less than 60 min, and full capacity was reached
      within 5 h. To the best of our knowledge, this is the first time that such
      performances have been achieved with NaBH(4). This demonstrates the potential of
      the strategy in leading to major advancements in the design of effective hydrogen
      storage materials from pristine borohydrides.

PMID- 22873408
TI  - BIK (NBK) is a mediator of the sensitivity of Fanconi anaemia group C
      lymphoblastoid cell lines to interstrand DNA cross-linking agents.
AB  - FA (Fanconi anaemia) is a rare hereditary disorder characterized by congenital
      malformations, progressive bone marrow failure and an extraordinary
      predisposition to develop cancer. At present, 15 genes have been related to this
      condition and mutations of them have also been found in different types of
      cancer. Bone marrow failure threatens the life of FA patients during the first
      decade of their life, but the mechanisms underlying this process are not
      completely understood. In the present study we investigate a possible imbalance
      between the expression of pro- and anti-apoptotic proteins as a cause for the
      hypersensitivity of FANCC (FA, complementation group C)-deficient cells to
      genotoxic stress. We found a BIK (Bcl-2 interacting killer) over-expression in
      lymphoblastoid cell lines derived from FA-C patients when compared with their
      phenotypically corrected counterparts. This overexpression has a transcriptional
      basis since the regulatory region of the gene shows higher activity in FANCC
      deficient cells. We demonstrate the involvement of BIK in the sensitivity of FA-C
      lymphoblasts to interstrand DNA cross-linking agents as it is induced by these
      drugs and interference of its expression in these cells preserves their viability
      and reduces apoptosis. We investigate the mechanism of BIK overexpression in
      FANCC-deficient cells by analysing the activity of many different signalling
      pathways in these cells. Finally, we provide evidence of a previously undescribed
      indirect epigenetic regulation of BIK in FA-C lymphoblasts mediated by DeltaNp73,
      an isoform of p73 lacking its transactivation domain that activates BIK through a
      proximal element in its promoter.

PMID- 22873410
TI  - Fluid management in critically ill patients: the role of extravascular lung
      water, abdominal hypertension, capillary leak, and fluid balance.
AB  - INTRODUCTION: Capillary leak in critically ill patients leads to interstitial
      edema. Fluid overload is independently associated with poor prognosis. Bedside
      measurement of intra-abdominal pressure (IAP), extravascular lung water index
      (EVLWI), fluid balance, and capillary leak index (CLI) may provide a valuable
      prognostic tool in mechanically ventilated patients. METHODS: We performed an
      observational study of 123 mechanically ventilated patients with extended
      hemodynamic monitoring, analyzing process-of-care variables for the first week of
      ICU admission. The primary outcome parameter was 28-day mortality. DeltamaxEVLWI
      indicated the maximum difference between EVLWI measurements during ICU stay.
      Patients with a DeltamaxEVLWI <-2 mL/kg were called 'responders'. CLI was defined
      as C-reactive protein (milligrams per deciliter) over albumin (grams per liter)
      ratio and conservative late fluid management (CLFM) as even-to-negative fluid
      balance on at least two consecutive days. RESULTS: CLI had a biphasic course.
      DeltamaxEVLWI was lower if CLFM was achieved and in survivors (-2.4 +/- 4.8 vs
      1.0 +/- 5.5 mL/kg, p = 0.001; -3.3 +/- 3.8 vs 2.5 +/- 5.3 mL/kg, p = 0.001,
      respectively). No CLFM achievement was associated with increased CLI and IAPmean
      on day 3 and higher risk to be nonresponder (odds ratio (OR) 2.76, p = 0.046; OR
      1.28, p = 0.011; OR 5.52, p = 0.001, respectively). Responders had more
      ventilator-free days during the first week (2.5 +/- 2.3 vs 1.5 +/- 2.3, p =
      0.023). Not achieving CLFM and being nonresponder were strong independent
      predictors of mortality (OR 9.34, p = 0.001 and OR 7.14, p = 0.001,
      respectively). CONCLUSION: There seems to be an important correlation between
      CLI, EVLWI kinetics, IAP, and fluid balance in mechanically ventilated patients,
      associated with organ dysfunction and poor prognosis. In this context, we
      introduce the global increased permeability syndrome.

PMID- 22873411
TI  - Intra-abdominal pressure measurement using the FoleyManometer does not increase
      the risk for urinary tract infection in critically ill patients.
AB  - OBJECTIVE: The aim of this study was to determine whether intra-abdominal
      pressure (IAP) monitoring using the FoleyManometer (Holtech Medical,
      Charlottenlund, Denmark) increases the risk of urinary tract infection (UTI).
      DESIGN: A retrospective database review was conducted. SETTING: The study was
      conducted in the 12-bed medical intensive care unit of ZNA Stuivenberg Hospital
      (Antwerp, Belgium), a tertiary hospital. PATIENTS: There were 5,890 patients
      admitted to the medical intensive care unit of which 1,097 patients underwent
      intrabladder pressure (IBP) monitoring as estimate for IAP. INTERVENTIONS: Crude
      and adjusted UTI rates were compared among patients undergoing IAP measurements
      with three different intrabladder methods: a modified homemade technique, a
      FoleyManometer with 35 ml reservoir, and a FoleyManometer low volume
      (FoleyManometerLV) with less than 10 ml priming volume. MEASUREMENTS AND RESULTS:
      Four consecutive time periods of 24 months were defined and compared with regard
      to IAP measurement: period 1 (2000-2001), during which IAP monitoring was not
      used routinely (which serves as a control group), was compared with period 2
      (2002-2003), using a modified homemade technique; period 3 (2004-2005),
      introducing the FoleyManometer; and finally period 4 (2006-2007), in which the
      FoleyManometerLV was introduced. The incidence of IBP measurements increased from
      1.4% in period 1 to 45.4% in period 4 (p < 0.001). At the same time, the
      Simplified Acute Physiology Score (version 2) (SAPS-II) increased significantly
      from 24.4 +/- 21.5 to 34.9 +/- 18.7 (p < 0.001) together with the percentage of
      ventilated patients from 18.6% to 40.7% (p < 0.001). In total, 1,097 patients had
      IAP measurements via the bladder. The UTI rates were adjusted for disease
      severity by multiplying each crude rate with the ratio of control versus study
      patient SAPS-II probability of mortality. Crude and adjusted UTI rates per 1,000
      catheter days (CD) were on average 16.1 and 12.8/1,000 CD, respectively, and were
      not significantly different between the four time periods. CONCLUSIONS:
      Intrabladder pressure monitoring as estimate for IAP either via a closed
      transducer technique or the closed FoleyManometer technique seems safe and does
      not alter the risk of UTI in critically ill patients.

PMID- 22873409
TI  - Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury.
AB  - BACKGROUND: Using a live imaging approach, we have previously shown that
      microglia activation after stroke is characterized by marked and long-term
      induction of the Toll-like receptor (TLR) 2 biophotonic signals. However, the
      role of TLR2 (and potentially other TLRs) beyond the acute innate immune response
      and as early neuroprotection against ischemic injury is not well understood.
      METHODS: TLR2-/- mice were subjected to transient middle cerebral artery
      occlusion followed by different reperfusion times. Analyses assessing microglial
      activation profile/innate immune response were performed using in situ
      hybridization, immunohistochemistry analysis, flow cytometry and inflammatory
      cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic
      brain injury were analyzed using a cresyl violet staining of brain sections with
      appropriate lesion size estimation. RESULTS: Here we report that TLR2 deficiency
      markedly affects post-stroke immune response resulting in delayed exacerbation of
      the ischemic injury. The temporal analysis of the microglia/macrophage activation
      profiles in TLR2-/- mice and age-matched controls revealed reduced
      microglia/macrophage activation after stroke, reduced capacity of resident
      microglia to proliferate as well as decreased levels of monocyte chemotactic
      protein-1 (MCP-1) and consequently lower levels of CD45(high)/CD11b(+) expressing
      cells as shown by flow cytometry analysis. Importantly, although acute ischemic
      lesions (24 to 72 h) were smaller in TLR2-/- mice, the observed alterations in
      innate immune response were more pronounced at later time points (at day 7) after
      initial stroke, which finally resulted in delayed exacerbation of ischemic lesion
      leading to larger chronic infarctions as compared with wild-type mice. Moreover,
      our results revealed that TLR2 deficiency is associated with significant decrease
      in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1
      (IGF-1), expressed by microglia in the areas both in and around ischemic lesion.
      CONCLUSION: Our results clearly suggest that optimal and timely microglial
      activation/innate immune response is needed to limit neuronal damage after
      stroke.

PMID- 22873412
TI  - Comparing intra-abdominal pressures in different body positions via a urinary
      catheter and nasogastric tube: a pilot study.
AB  - OBJECTIVES: Intra-abdominal pressure (IAP) is most commonly measured via the
      bladder with the patient in the supine position. In the ICU, patients are nursed
      with the head of the bed elevated at 30 degrees  (HOB30) to reduce the risk of
      ventilator-associated pneumonia. This study investigated whether gastric pressure
      at HOB30 can be used as a surrogate measure of IAP via the bladder in the supine
      position. METHODS: A prospective observational study was conducted in a single
      centre intensive care unit. A total of 20 patients were included. IAP was
      recorded simultaneously via the bladder catheter (bladder pressure, IBP) and via
      nasogastric tube (gastric pressures, IGP) in the supine and HOB30 position. Each
      patient had three sets of IAP measurements performed at least 4 h apart. RESULTS:
      In the supine position, mean IBP was 12.3 +/- 4.5 mmHg compared to IGP of 11.8 +/
      4.7 mmHg. The bias between the two groups was 0.5 and precision of 3.7 (LA, -6.8
      to 7.5 mmHg). At 30 degrees, mean IBP was 15.8 +/- 4.9 mmHg compared to IGP of
      13.1 +/- 6.1 mmHg. The bias between both groups was 2.7 with a precision of 5.5
      (LA, -8.0 to 13.5). Comparing IBP in the supine position with IGP at 30 degrees 
      showed a bias of -0.8 and precision of 5.6 (LA, -10.1 to 11.6 mmHg). CONCLUSION:
      IAP measured via a nasogastric tube was less influenced by changing the body
      position from supine to HOB30 than was bladder pressure.

PMID- 22873413
TI  - The effect of body position on compartmental intra-abdominal pressure following
      liver transplantation.
AB  - BACKGROUND: Current assumptions rely on intra-abdominal pressure (IAP) being
      uniform across the abdominal cavity. The abdominal contents are, however, a
      heterogeneous mix of solid, liquid and gas, and pressure transmission may not be
      uniform. The current study examines the upper and lower IAP following liver
      transplantation. METHODS: IAP was measured directly via intra-peritoneal
      catheters placed at the liver and outside the bladder. Compartmental pressure
      data were recorded at 10-min intervals for up to 72 h following surgery, and the
      effect of intermittent posture change on compartmental pressures was also
      studied. Pelvic intra-peritoneal pressure was compared to intra-bladder pressure
      measured via a FoleyManometer. RESULTS: A significant variation in upper and
      lower IAP of 18% was observed with a range of differences of 0 to 16 mmHg. A
      sustained difference in inter-compartmental pressure of 4 mmHg or more was
      present for 23% of the study time. Head-up positioning at 30 degrees  provided a
      protective effect on upper intra-abdominal pressure, resulting in a significant
      reduction in all patients. There was excellent agreement between intra-bladder
      and pelvic pressure. CONCLUSIONS: A clinically significant variation in inter
      compartmental pressure exists following liver transplantation, which can be
      manipulated by changes to body position. The existence of regional pressure
      differences suggests that IAP monitoring at the bladder alone may under-diagnose
      intra-abdominal hypertension and abdominal compartment syndrome in these
      patients. The upper and lower abdomen may need to be considered as separate
      entities in certain conditions.

PMID- 22873415
TI  - Moderate intra-abdominal hypertension is associated with an increased lactate
      pyruvate ratio in the rectus abdominis muscle tissue: a pilot study during
      laparoscopic surgery.
AB  - BACKGROUND: The development of intra-abdominal hypertension [IAH] in critically
      ill patients admitted to the ICU is an independent predictor of mortality. In an
      attempt to find an early, clinically relevant metabolic signal of modest IAH, we
      investigated abdominal wall metabolite concentrations in a small group of
      patients undergoing laparoscopic surgery. We hypothesized that elevated intra
      abdominal pressure [IAP] due to pneumoperitoneum leads to an increased
      lactate/pyruvate [L/P] ratio in the rectus abdominis muscle [RAM], indicating
      anaerobic metabolism. METHOD: Six patients scheduled for elective laparoscopic
      gastric fundoplication were studied. Two hours before surgery, a microdialysis
      catheter (CMA 60, CMA Small Systems AB, Solna, Sweden) was inserted into the RAM
      under local anaesthesia. Catheter placement was confirmed by ultrasound. The
      microdialysis perfusion rate was set at 0.3 MUL/min. Dialysate was collected
      hourly prior to pneumoperitoneum, during pneumoperitoneum, and for 2 h after
      pneumoperitoneum resolution. IAP was maintained at 12 to 13 mmHg during the
      surgery. The glucose, glycerol, pyruvate and lactate contents of the dialysate
      were measured. RESULTS: The median (interquartile range) L/P ratio was 10.3 (7.1
      to 15.5) mmol/L at baseline. One hour of pneumoperitoneum increased the L/P ratio
      to 16.0 (13.6 to 35.3) mmol/L (p = 0.03). The median pneumoperitoneum duration
      was 86 (77 to 111) min. The L/P ratio at 2 h post-pneumoperitoneum was not
      different from that at baseline (p = 1.0). No changes in glycerol or glucose
      levels were observed. CONCLUSIONS: IAH of 12 to 13 mmHg, even for a relatively
      short duration, is associated with metabolic changes in the abdominal wall muscle
      tissue of patients undergoing laparoscopic surgery. We suggest that tissue
      hypoperfusion occurs even during a modest increase in IAP, and intramuscular
      metabolic monitoring could therefore serve as an early warning sign of
      deteriorating tissue perfusion.

PMID- 22873414
TI  - Effects of zero reference position on bladder pressure measurements: an
      observational study.
AB  - BACKGROUND: Although the World Society for Abdominal Compartment Syndrome in its
      guidelines recommends midaxillary line (MAL) as zero reference level in intra
      abdominal pressure (IAP) measurements in aiming at standardizing the technique,
      evidence supporting this suggestion is scarce. The aim of this study is to study
      if the zero reference position influences bladder pressure measurements as
      estimate for IAP. METHODS: The IAP of 100 surgical patients was measured during
      the first 24 h of admission to the surgical intensive care unit of General
      Calixto Garcia Hospital in Havana (Cuba) following laparotomy. The period was
      January 2009 to January 2010. The IAP was measured twice with a six-hour interval
      using the transurethral technique with a priming volume of 25 ml. IAP was first
      measured with the zero reference level placed at MAL (IAPMAL), followed by a
      second measurement at the level of the symphysis pubis (SP) after 3 minutes
      (IAPSP). Correlations were made between IAP and body mass index (BMI), type of
      surgery, gender, and age. RESULTS: Mean IAPMAL was 8.5 +/- 2.8 mmHg vs. IAPSP 6.5
      +/- 2.8 mmHg (p < 0.0001). The bias between measurements was 2.0 +/- 1.5, 95%
      confidence interval of 1.4 to 3.0, upper limit of 4.9, lower limit of -0.9, and a
      percentage error of 35.1%. IAPMAL was consistently higher than IAPSP regardless
      of the type of surgery. The BMI correlated with IAP values regardless of the zero
      reference level (R2 = 0.4 and 0.3 with IAPMAL and IAPSP respectively, p <
      0.0001). CONCLUSIONS: The zero reference level has an important impact on IAP
      measurement in surgical patients after laparotomy and can potentially lead to
      over or underestimation. Further anthropometric studies are needed with regard to
      the relative MAL and SP zero reference position in relation to the theoretical
      ideal reference level at midpoint of the abdomen. Until better evidence is
      available, MAL remains the recommended zero reference position due to its best
      anatomical localization at iliac crest.

PMID- 22873416
TI  - Aiming for a negative fluid balance in patients with acute lung injury and
      increased intra-abdominal pressure: a pilot study looking at the effects of PAL
      treatment.
AB  - INTRODUCTION: Achievement of a negative fluid balance in patients with capillary
      leak is associated with improved outcome. We investigated the effects of a multi
      modal restrictive fluid strategy aiming for negative fluid balance in patients
      with acute lung injury (ALI). METHODS: In this retrospective matched case-control
      study, we included 114 mechanically ventilated (MV) patients with ALI. We
      compared outcomes between a group of 57 patients receiving PAL-treatment (PAL
      group) and a matched control group, abstracted from a historical cohort. PAL
      treatment combines high levels of positive end-expiratory pressure, small volume
      resuscitation with hyperoncotic albumin, and fluid removal with furosemide
      (Lasix(r)) or ultrafiltration. Effects on extravascular lung water index (EVLWI),
      intra-abdominal pressure (IAP), organ function, and vasopressor therapy were
      recorded during 1 week. The primary outcome parameter was 28-day mortality.
      RESULTS: At baseline, no significant intergroup differences were found, except
      for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 +/- 84.5 vs 256.5
      +/- 152.7, p = 0.001; 10.0 +/- 4.2 vs 8.0 +/- 3.7 mmHg, p = 0.013, respectively).
      After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and
      cumulative fluid balance (-4.2 +/- 5.6 vs -1.1 +/- 3.7 mL/kg, p = 0.006; -0.4 +/-
      3.6 vs 1.8 +/- 3.8 mmHg, p = 0.007; -1,451 +/- 7,761 vs 8,027 +/- 5,254 mL, p <
      0.001). Repercussions on cardiovascular and renal function were limited. PAL
      treated patients required fewer days of intensive care unit admission and days on
      MV (23.6 +/- 15 vs 37.1 +/- 19.9 days, p = 0.006; 14.6 +/- 10.7 vs 25.5 +/- 20.2
      days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034).
      CONCLUSION: PAL-treatment in patients with ALI is associated with a negative
      fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes
      without compromising organ function.

PMID- 22873417
TI  - Influence of two different levels of intra-abdominal hypertension on bacterial
      translocation in a porcine model.
AB  - BACKGROUND: The purpose of the present study was to quantify bacterial
      translocation to mesenteric lymph nodes due to different levels of intra
      abdominal hypertension (IAH; 15 vs. 30 mmHg) lasting for 24 h in a porcine model.
      METHODS: We examined 18 anesthetized and intubated pigs (52.3 +/- 4.7 kg) which
      were randomly allocated to three experimental groups (each n = 6) and studied
      over a period of 24 h. After preparation and establishing a steady state, the
      intra-abdominal pressure (IAP) was increased stepwise to 30 mmHg in six animals
      using a carbon dioxide (CO2) insufflator (IAP-30 group). In the second group, IAP
      was increased to 15 mmHg (IAP-15 group), while IAP remained unchanged in another
      six pigs (control group). Using a pulse contour cardiac output (PiCCO(r))
      monitoring system, hemodynamic parameters as well as blood gases were recorded
      periodically. Moreover, peripheral and portal vein blood samples were taken for
      microbiological examinations. Lymph nodes from the ileocecal junction were
      sampled during an intra-vital laparotomy at the end of the observational period.
      After sacrificing the animals, bowel tissue samples and corresponding mesenteric
      lymph nodes (MLN) were extracted for histopathological and microbiological
      analyses. RESULTS: Cardiac output decreased in all groups. In IAP-30 animals,
      volumetric preload indices significantly decreased, while those of IAP-15 pigs
      did not differ from those of controls. Under IAH, the mean arterial pressure
      (MAP) in the IAP-30 group declined, while MAP in the IAP-15 group was
      significantly elevated (controls unchanged). PO2 and PCO2 remained unchanged. The
      grade of ischemic damage of the intestines (histopathologically quantified using
      the Park score) increased significantly with different IAH levels. Accordingly,
      the amount of translocated bacteria in intestinal wall specimens as well as in
      MLN significantly increased with the level of IAH. Lymph node cultures confirmed
      the relation between bacterial translocation (BT) and IAP. The most often
      cultivated species were Escherichia coli, Staphylococcus, Clostridium,
      Pasteurella, and Streptococcus. Bacteremia was detected only occasionally in all
      three groups (not significantly different) showing gut-derived bacteria such as
      Proteus, Klebsiella, and E. coli spp. CONCLUSION: In this porcine model, a higher
      level of ischemic damage and more BT were observed in animals subjected to an IAP
      of 30 mmHg when compared to animals subjected to an IAP of 15 mmHg or controls.

PMID- 22873418
TI  - Intra-abdominal hypertension in patients with sellar region tumors.
AB  - BACKGROUND: Data on intra-abdominal hypertension [IAH] and secondary abdominal
      compartment syndrome [ACS] due to neurological insults are limited. METHODS: This
      was a prospective observational study conducted between January 2010 and January
      2011 in the neurological ICU [NICU]. Forty-one consecutive patients with sellar
      region tumors [SRT] were enrolled into the study. If conservative therapy was
      ineffective in patients with ACS, thoracic epidural anesthesia [EA] was
      performed. Primary endpoint was defined as the efficacy of conservative treatment
      and EA in patients with IAH and ACS; secondary endpoint, the influence of IAH and
      ACS on outcomes. RESULTS: Of the 41 patients, 13 (31.7%) had normal intra
      abdominal pressure and 28 (68.3%) developed IAH, of whom 9 (22%) had ACS (group
      II). On average, IAH developed on the second postoperative day, while ACS,
      between the third and the fifth day. Multiple organ dysfunction developed in 3
      (23.1%) patients of group I and in 23 (82%) patients of group II (p = 0.0003).
      Ileus due to gastrointestinal dysmotility was present in 6 (46.2%) patients of
      group I and in all patients of group II (p = 0.0001). Significant risk factors
      for ileus were diencephalon dysfunction (whole group - in 33 patients (80.5%);
      group I - in 6 patients (46.2%); group II - in 27 patients (96.4%), p = 0.0002)
      and sepsis (whole group - in 8 patients (19.5%); group I - no cases; group II -
      in 8 patients (28.6%), p = 0.03). Conservative treatment was effective in the
      majority of patients (78.9%) with IAH and only in 3 (33%) patients with ACS.
      Thoracic EA was performed in four patients with ACS with success. Length of stay
      in the NICU was 6.5 +/- 4.6 days in group I and 24.1 +/- 25.7 (p = 0.02) days in
      group II. Five out of nine (55.6%) patients with ACS died. None of these patients
      received EA. All patients with EA had favorable outcomes. CONCLUSION: The
      development of IAH is common after SRT surgery. If conservative treatment is
      ineffective, EA can be considered in patients with secondary ACS. Further studies
      are warranted.

PMID- 22873419
TI  - Incidence and prognosis of intra-abdominal hypertension in critically ill medical
      patients: a prospective epidemiological study.
AB  - INTRODUCTION: The aim of this study was to determine the incidence of intra
      abdominal hypertension (IAH) in patients with two or more categorized risk
      factors (CRF) for IAH, and their morbidity and mortality during their intensive
      care unit (ICU) stay. METHODS: Prospective cohort study carried out at a medical
      ICU. A total of 151 medical patients were enrolled during a period of 3 months.
      After ICU whole staff training, we conducted daily screening of the four CRF for
      IAH based on the World Society of Abdominal Compartment Syndrome (WSACS)
      guidelines (namely, diminished abdominal wall compliance, increased intraluminal
      content, increased abdominal content, and capillary leak syndrome or fluid
      resuscitation). In those patients with risk factors of at least two different
      categories (>=2 CRF), intra-abdominal pressure (IAP) was measured every 8 h
      during ICU stay. Data included demographics, main diagnosis on admission,
      severity scores, cumulative fluid balance, daily mean IAP, resolution of IAH,
      days of ICU and hospital stay, and mortality. RESULTS: Eighty-seven patients
      (57.6%) had >=2 CRF for IAH, 59 (67.8%) out of whom developed IAH. Patients with
      >=2 CRF had a significantly higher mortality rate (41.4 vs. 14.3%, p < 0.001).
      Patients with IAH had higher body mass index, severity scores, organ
      dysfunctions/failures, number of CRF for IAH, days of ICU/hospital stay and
      hospital mortality rate (45.8 vs. 32.1%, p = 0.22). Non-resolution of IAH was
      associated with a higher mortality rate (64.7 vs. 35.3%, p = 0.001). None of the
      cohort patients developed abdominal compartment syndrome. The multivariate
      analysis showed that IAH development (odds ratio (OR) 4.09; 95% confidence
      interval (CI) 0.83-20.12) was a non-independent risk factor for mortality, and
      its non-resolution (OR 13.15; 95% CI 22.13-81.92) was an independent risk factor
      for mortality. CONCLUSIONS: Critically ill medical patients admitted to ICU with
      >=2 CRF have high morbidity, mortality rate, and incidence of IAH, so IAP should
      be measured and monitored as recommended by the WSACS. Our study highlights the
      importance of implementing screening and assessment protocols for an early
      diagnosis of IAH.

PMID- 22873420
TI  - Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients
      with septic shock.
AB  - BACKGROUND: The importance of intra-abdominal pressure (IAP) and abdominal
      perfusion pressure (APP) in cirrhotic patients with septic shock is not well
      studied. We evaluated the relationship between IAP and APP and outcomes of
      cirrhotic septic patients, and assessed the ability of these measures compared to
      other common resuscitative endpoints to differentiate survivors from
      nonsurvivors. METHODS: This study was a post hoc analysis of a randomized double
      blind placebo-controlled trial in which mean arterial pressure (MAP), central
      venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic
      septic patients admitted to the intensive care unit. APP was calculated as MAP -
      IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP >= 12 mmHg, and
      abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and
      hospital mortality, need for renal replacement therapy (RRT) and ventilator- and
      vasopressor-free days. RESULTS: IAH prevalence on the first ICU day was 82%, and
      incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH
      patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005),
      required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and
      vasopressor-free days. On a multivariate logistic regression analysis, IAH was an
      independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95%
      confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78;
      95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves,
      IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01),
      Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02),
      but not MAP, differentiated survivors from nonsurvivors. CONCLUSIONS: IAH is
      highly prevalent in cirrhotic patients with septic shock and is associated with
      increased ICU morbidity and mortality.

PMID- 22873421
TI  - Intra-abdominal pressure, intra-abdominal hypertension, and pregnancy: a review.
AB  - The last several decades have seen many advances in the recognition and
      prevention of the abdominal compartment syndrome (ACS) and its precursor, intra
      abdominal hypertension (IAH). There has also been a relative explosion of
      knowledge in the critical care, trauma, and surgical populations, and the
      inception of a society dedicated to its understanding, the World Society of the
      Abdominal Compartment Syndrome (WSACS). However, there has been almost no
      recognition or appreciation of the potential presence, influence, and management
      of intra-abdominal pressure (IAP), IAH, and ACS in pregnancy. This review
      highlights the importance and relevance of IAP in the critically ill parturient,
      the current lack of normative IAP values in pregnancy today, along with a review
      of the potential relationship between IAH and maternal diseases such as
      preeclampsia-eclampsia and its potential impact on fetal development. Finally,
      current IAP measurement guidelines are questioned, as they do not take into
      account the gravid uterus and its mechanical impact on intra-vesicular pressure.

PMID- 22873422
TI  - Pediatric critical care nurses' experience with abdominal compartment syndrome.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is a syndrome associated with
      multi-system effects of elevated intra-abdominal pressure (IAP) in critically ill
      children. It has a 90-100% mortality rate if not recognized and treated promptly.
      Measuring IAP helps identify patients developing intra-abdominal hypertension
      (IAH) which allows for timely intervention before progression to ACS. IAP helps
      identify ACS and guides its medical and surgical management. IAP is often
      measured by the bedside nurse in the intensive care unit. Pediatric critical care
      nurses (PCCN) play a key role in managing critically ill patients and recognizing
      potential causes for clinical deterioration such as ACS therefore should be
      knowledgeable about this entity. OBJECTIVE: The aim of this study was to assess
      the awareness and current knowledge of ACS among PCCN. METHODS: A ten-item
      written questionnaire was distributed at a National Critical Care Conference in
      2006 and again in 2010. Participants of the conference voluntarily completed and
      immediately returned the survey. Results from the two questionnaires were
      compared. RESULTS: Sixty-two percent of 691 questionnaires were completed. The
      awareness of ACS improved from 69.3% in 2006 to 87.8% in 2010 (p < 0.001) among
      PCCN. "Years in practice" influenced awareness of ACS. Nurses working for 5-10
      and > 10 years were, respectively, 2.34 and 1.89 times more likely to be aware of
      ACS than those working for < 5 years. Hands-on experience managing a child with
      ACS by PCCN also improved from 49.1% to 67.9% (p < 0.001) but remains low. The
      number of participants who never measured IAP fell from 27.3% to 19.1% (p =
      0.101). The most common method being used to measure IAP is the bladder method.
      Knowledge of the definition of ACS remains poor with only 13.2% associating the
      definition of ACS with organ dysfunction in 2010 which was even lower than in
      2006. CONCLUSIONS: There is increasing awareness of ACS and experience in its
      management among PCCN. However, few PCCN correctly understand the definition of
      ACS. Since recognition of IAH and early intervention can reduce morbidity and
      mortality in critically ill patients, further educational efforts should be
      directed toward improving the knowledge and recognition of ACS by PCCN.

PMID- 22873423
TI  - Recognition and management of abdominal compartment syndrome among German
      anesthetists and surgeons: a national survey.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is a life threatening condition
      that may affect any critically ill patient. Little is known about the recognition
      and management of ACS in Germany. METHODS: A questionnaire was mailed to
      departments of surgery and anesthesia from German hospitals with more than 450
      beds. RESULTS: Replies (113) were received from 222 eligible hospitals (51%).
      Most respondents (95%) indicated that ACS plays a role in their clinical
      practice. Intra-abdominal pressure (IAP) is not measured at all by 26%, while it
      is routinely done by 30%. IAP is mostly (94%) assessed via the intra-vesical
      route. Of the respondents, 41% only measure IAP in patients expected to develop
      ACS; 64% states that a simpler, more standardized application of IAP measurement
      would lead to increased use in daily clinical practice. CONCLUSIONS: German
      anesthesiologists and surgeons are familiar with ACS. However, approximately one
      fourth never measures IAP, and there is considerable uncertainty regarding which
      patients are at risk as well as how often IAP should be measured in them.

PMID- 22873424
TI  - Recognition and management of abdominal compartment syndrome among German
      pediatric intensivists: results of a national survey.
AB  - INTRODUCTION: Several decades ago, the beneficial effects of goal-directed
      therapy, which include decompressive laparotomy (DL) and open abdomen procedures
      in cases of intra-abdominal hypertension (IAH) in children, were proven in the
      context of closures of abdominal wall defects and large-for-size organ
      transplantations. Different neonatologic and pediatric disease patterns are also
      known to be capable of increasing intra-abdominal pressure (IAP). Nevertheless, a
      considerable knowledge transfer regarding such risk factors has hardly taken
      place. When left undetected and untreated, IAH threatens to evolve into abdominal
      compartment syndrome (ACS), which is accompanied by a mortality rate of up to 60%
      in children. Therefore, the present study looks at the recognition and knowledge
      of IAH/ACS among German pediatric intensivists. METHODS: In June 2010, a
      questionnaire was mailed to the heads of pediatric intensive care units of 205
      German pediatric hospitals. RESULTS: The response rate was 62%. At least one case
      of IAH was reported by 36% of respondents; at least one case of ACS, by 25%.
      Compared with adolescents, younger critically ill children appeared to develop
      IAH/ACS more often. Routine measurements of IAP were said to be performed by 20%
      of respondents. Bladder pressure was used most frequently (96%) to assess IAP.
      Some respondents (17%) only measured IAP in cases of organ dysfunction and
      failure. In 2009, the year preceding this study, 21% of respondents claimed to
      have performed a DL. Surgical decompression was indicated if signs of organ
      dysfunction were present. This was also done in cases of at least grade III IAH
      (IAP > 15 mmHg) without organ impairment. CONCLUSIONS: Although awareness among
      pediatricians appears to have been increasing over the last decade, definitions
      and guidelines regarding the diagnosis and management of IAH/ACS are not applied
      uniformly. This variability could express an ever present lack of awareness and
      solid prospective data.

PMID- 22873426
TI  - Database of small molecule thermochemistry for combustion.
AB  - High-accuracy ab initio thermochemistry is presented for 219 small molecules
      relevant in combustion chemistry, including many radical, biradical, and triplet
      species. These values are critical for accurate kinetic modeling. The
      RQCISD(T)/cc-PVinfinityQZ//B3LYP/6-311++G(d,p) method was used to compute the
      electronic energies. A bond additivity correction for this method has been
      developed to remove systematic errors in the enthalpy calculations, using the
      Active Thermochemical Tables as reference values. On the basis of comparison with
      the benchmark data, the 3sigma uncertainty in the standard-state heat of
      formation is 0.9 kcal/mol, or within chemical accuracy. An uncertainty analysis
      is presented for the entropy and heat capacity. In many cases, the present values
      are the most accurate and comprehensive numbers available. The present work is
      compared to several published databases. In some cases, there are large
      discrepancies and errors in published databases; the present work helps to
      resolve these problems. 

PMID- 22873425
TI  - Should we measure intra-abdominal pressures in every intensive care patient?
AB  - Intra-abdominal pressure (IAP) is seldom measured by default in intensive care
      patients. This review summarises the current evidence on the prevalence and risk
      factors of intra-abdominal hypertension (IAH) to assist the decision-making for
      IAP monitoring.IAH occurs in 20% to 40% of intensive care patients. High body
      mass index (BMI), abdominal surgery, liver dysfunction/ascites,
      hypotension/vasoactive therapy, respiratory failure and excessive fluid balance
      are risk factors of IAH in the general ICU population. IAP monitoring is strongly
      supported in mechanically ventilated patients with severe burns, severe trauma,
      severe acute pancreatitis, liver failure or ruptured aortic aneurysms. The risk
      of developing IAH is minimal in mechanically ventilated patients with positive
      end-expiratory pressure < 10 cmH2O, PaO2/FiO2 > 300, and BMI < 30 and without
      pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding
      or laparotomy and the use of vasopressors/inotropes on admission. In these
      patients, omitting IAP measurements might be considered.In conclusions, clear
      guidelines to select the patients in whom IAP measurements should be performed
      cannot be given at present. In addition to IAP measurements in at-risk patients,
      a clinical assessment of the signs of IAH should be a part of every ICU patient's
      bedside evaluation, leading to prompt IAP monitoring in case of the slightest
      suspicion of IAH development.

PMID- 22873427
TI  - Laser acupuncture for the treatment of asthma in children: a systematic review of
      randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVES: Laser acupuncture has often been recommended as a
      treatment of asthma. The technique is noninvasive, and seems particularly
      suitable for children. However, the results from several clinical trials are
      contradictory. The objective of this review was to assess the effectiveness of
      laser acupuncture in the treatment of childhood asthma. METHODS: Literature
      searches of electronic database were conducted in The Cochrane Library, Medline,
      EMBASE, AMED, CINAHL, and two Chinese literature databases (CNKI and VIP) up to
      February 2012. Randomized controlled trials (RCTs) testing laser acupuncture for
      asthma in children were included. No language restrictions were applied. Three
      authors independently selected articles, extracted data, and assessed trial
      quality. RESULTS: Our searches identified 13 potential eligible studies, of which
      three with a total number of 176 patients met our inclusion criteria. The quality
      of included RCTs were low. One RCT with a parallel group design showed positive
      results, while two crossover RCTs generated negative results. There was variation
      in the type of patients, the interventions, and outcome measures. Because of the
      significant clinical and methodological heterogeneity, no meta-analysis was
      performed. CONCLUSIONS: The number of RCTs and their total sample sizes are
      small; and their methodological quality is low. Therefore, no compelling evidence
      exists to suggest that laser acupuncture is not an effective treatment for
      childhood asthma. Further rigorous studies are warranted.

PMID- 22873428
TI  - Adsorption of phosphonate antiscalant from reverse osmosis membrane concentrate
      onto granular ferric hydroxide.
AB  - Adsorptive removal of antiscalants offers a promising way to improve current
      reverse osmosis (RO) concentrate treatment processes and enables the reuse of the
      antiscalant in the RO desalination process. This work investigates the adsorption
      and desorption of the phosphonate antiscalant nitrilotris(methylenephosphonic
      acid) (NTMP) from RO membrane concentrate onto granular ferric hydroxide (GFH), a
      material that consists predominantly of akaganeite. The kinetics of the
      adsorption of NTMP onto GFH was predicted fairly well with two models that
      consider either combined film-pore or combined film-surface diffusion as the main
      mechanism for mass transport. It is also demonstrated that NTMP is preferentially
      adsorbed over sulfate by GFH at pH 7.85. The presence of calcium causes a
      transformation in the equilibrium adsorption isotherm from a Langmuir type to a
      Freundlich type with much higher adsorption capacities. Furthermore, calcium also
      increases the rate of adsorption substantially. GFH is reusable after
      regeneration with sodium hydroxide solution, indicating that NTMP can be
      potentially recovered from the RO concentrate. This work shows that GFH is a
      promising adsorbent for the removal and recovery of NTMP antiscalant from RO
      membrane concentrates.

PMID- 22873430
TI  - Transparency for clinical trials--the TEST Act.

PMID- 22873429
TI  - When the cost curve bent--pre-recession moderation in health care spending.

PMID- 22873431
TI  - Binding selectivity of dibenzo-18-crown-6 for alkali metal cations in aqueous
      solution: A density functional theory study using a continuum solvation model.
AB  - BACKGROUND: Dibenzo-18-crown-6 (DB18C6) exhibits the binding selectivity for
      alkali metal cations in solution phase. In this study, we investigate the main
      forces that determine the binding selectivity of DB18C6 for the metal cations in
      aqueous solution using the density functional theory (DFT) and the conductor-like
      polarizable continuum model (CPCM). RESULTS: The bond dissociation free energies
      (BDFE) of DB18C6 complexes with alkali metal cations (M+-DB18C6, M = Li, Na, K,
      Rb, and Cs) in aqueous solution are calculated at the B3LYP/6
      311++G(d,p)//B3LYP/6-31 + G(d) level using the CPCM. It is found that the
      theoretical BDFE is the largest for K+-DB18C6 and decreases as the size of the
      metal cation gets larger or smaller than that of K+, which agrees well with
      previous experimental results. CONCLUSION: The solvation energy of M+-DB18C6 in
      aqueous solution plays a key role in determining the binding selectivity of
      DB18C6. In particular, the non-electrostatic dispersion interaction between the
      solute and solvent, which depends strongly on the complex structure, is largely
      responsible for the different solvation energies of M+-DB18C6. This study shows
      that the implicit solvation model like the CPCM works reasonably well in
      predicting the binding selectivity of DB18C6 in aqueous solution.

PMID- 22873432
TI  - Cytotoxic effects of ZnO hierarchical architectures on RSC96 Schwann cells.
AB  - The alteration in intracellular Zn2+ homeostasis is attributed to the generation
      of intracellular reactive oxygen species, which subsequently results in oxidative
      damage of organelles and cell apoptosis. In this work, the neurotoxic effects of
      ZnO hierarchical architectures (nanoparticles and microspheres, the prism-like
      and flower-like structures) were evaluated through the 3-(4, 5-dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide assay using RSC96 Schwann cells as the
      model. Cell apoptosis and cell cycle were detected using flow cytometry. The
      concentration of Zn2+ in the culture media was monitored using atomic absorption
      spectrometry. The results show that ZnO nanoparticles and microspheres displayed
      significant cytotoxic effects on RSC96 Schwann cells in dose- and time-dependent
      manners, whereas no or low cytotoxic effect was observed when the cells were
      treated with the prism-like and flower-like ZnO. A remarkable cell apoptosis and
      G2/M cell cycle arrest were observed when RSC96 Schwann cells were exposed to ZnO
      nanoparticles and microspheres at a dose of 80 MUg/mL for 12 h. The time
      dependent increase of Zn2+ concentration in the culture media suggests that the
      cytotoxic effects were associated with the decomposition of ZnO hierarchical
      architecture and the subsequent release of Zn2+. These results provide new
      insights into the cytotoxic effects of complex ZnO architectures, which could be
      prominently dominated by nanoscale building blocks.

PMID- 22873433
TI  - Editorial.

PMID- 22873434
TI  - The role of host population heterogeneity in the evolution of virulence.
AB  - I examine here the effects of host heterogeneity in the growth of immune response
      on the evolution and co-evolution of virulence. The analysis is based on an
      extension of the 'nested model' by Gilchrist and Sasaki [Modeling host-parasite
      coevolution, J. Theor. Biol. 218 (2002), pp. 289-308]; the criteria for host and
      parasite evolution, in the paradigm of adaptive dynamics, for that model are
      derived in generality. Host heterogeneity is assumed to be fixed at birth
      according to a lognormal distribution or to the presence of two discrete types.
      In both cases, it is found that host heterogeneity determines a dramatic decrease
      in pathogen virulence, since pathogens will tune to the 'weakest' hosts. Finally
      we clarify how contrasting results present in the literature are due to different
      modelling assumptions.

PMID- 22873435
TI  - Evolution of unconditional dispersal in periodic environments.
AB  - Organisms modulate their fitness in heterogeneous environments by dispersing.
      Prior work shows that there is selection against 'unconditional' dispersal in
      spatially heterogeneous environments. 'Unconditional' means individuals disperse
      at a rate independent of their location. We prove that if within-patch fitness
      varies spatially and between two values temporally, then there is selection for
      unconditional dispersal: any evolutionarily stable strategy (ESS) or
      evolutionarily stable coalition (ESC) includes a dispersive phenotype. Moreover,
      at this ESS or ESC, there is at least one sink patch (i.e. geometric mean of
      fitness less than one) and no sources patches (i.e. geometric mean of fitness
      greater than one). These results coupled with simulations suggest that spatial
      temporal heterogeneity is due to abiotic forcing result in either an ESS with a
      dispersive phenotype or an ESC with sedentary and dispersive phenotypes. In
      contrast, the spatial-temporal heterogeneity due to biotic interactions can
      select for higher dispersal rates that ultimately spatially synchronize
      population dynamics.

PMID- 22873436
TI  - Under which conditions is character displacement a likely outcome of secondary
      contact?
AB  - Sympatric character displacement is one possible mechanism that prevents
      competitive exclusion. This mechanism is thought to be behind the radiation of
      Darwin's finches, where character displacement is assumed to have followed
      secondary contact of ecologically similar species. We use a model to evaluate
      under which ecological and environmental conditions this mechanism is likely.
      Using the adaptive dynamics theory, we analyse different ecological models
      embedded in the secondary contact scenario. We highlight two necessary conditions
      for character displacement in sympatry: (i) very strong premating isolation
      between the two populations, and (ii) secondary contact to occur at an
      evolutionary branching point. Character displacement is then driven by adaptation
      to interspecific competition. We determine how ecological and environmental
      parameters influence the probability of ecological divergence. Finally, we
      discuss the likelihood of sympatric character displacement under disruptive
      selection in natural populations.

PMID- 22873437
TI  - Stochasticity in the adaptive dynamics of evolution: the bare bones.
AB  - First a population model with one single type of individuals is considered.
      Individuals reproduce asexually by splitting into two, with a population-size
      dependent probability. Population extinction, growth and persistence are studied.
      Subsequently the results are extended to such a population with two competing
      morphs and are applied to a simple model, where morphs arise through mutation.
      The movement in the trait space of a monomorphic population and its possible
      branching into polymorphism are discussed. This is a first report. It purports to
      display the basic conceptual structure of a simple exact probabilistic
      formulation of adaptive dynamics.

PMID- 22873438
TI  - A simple fitness proxy for structured populations with continuous traits, with
      case studies on the evolution of haplo-diploids and genetic dimorphisms.
AB  - For structured populations in equilibrium with everybody born equal, ln(R (0)) is
      a useful fitness proxy for evolutionarily steady strategy (ESS) and most adaptive
      dynamics calculations, with R (0) the average lifetime number of offspring in the
      clonal and haploid cases, and half the average lifetime number of offspring
      fathered or mothered for Mendelian diploids. When individuals have variable birth
      states, as is, for example, the case in spatial models, R (0) is itself an
      eigenvalue, which usually cannot be expressed explicitly in the trait vectors
      under consideration. In that case, Q(Y| X):=-det (I-L(Y| X)) can often be used as
      fitness proxy, with L the next-generation matrix for a potential mutant
      characterized by the trait vector Y in the (constant) environment engendered by a
      resident characterized by X. If the trait space is connected, global
      uninvadability can be determined from it. Moreover, it can be used in all the
      usual local calculations like the determination of evolutionarily singular trait
      vectors and their local invadability and attractivity. We conclude with three
      extended case studies demonstrating the usefulness of Q: the calculation of ESSs
      under haplo-diploid genetics (I), of evolutionarily steady genetic dimorphisms
      (ESDs) with a priori proportionality of macro- and micro-gametic outputs (an
      assumption that is generally made but the fulfilment of which is a priori highly
      exceptional) (II), and of ESDs without such proportionality (III). These case
      studies should also have some interest in their own right for the spelled out
      calculation recipes and their underlying modelling methodology.

PMID- 22873439
TI  - Variability within families and the evolution of body-condition-dependent
      dispersal.
AB  - In a population where body condition varies between and within families, we
      investigate the evolution of dispersal as a function of body condition
      ('strength', e.g. body size). Strong individuals are better competitors in a
      weighted lottery. If body condition does not influence survival during dispersal,
      then there is no unique evolutionarily stable strategy. Instead, there are
      infinitely many dispersal strategies that all lead to the same non-dispersing
      weight in a patch. These strategies are all selectively neutral but determine
      wildly different relationships between body condition and disposal probability.
      This may explain why there is no consistent pattern between body condition and
      dispersal found in empirical studies. If body condition influences survival
      during dispersal, then neutrality is removed and individuals with higher survival
      probability disperse. Dispersal may be the competitively weaker individuals if
      smaller body size helps to avoid dispersal risks.

PMID- 22873440
TI  - Maternal "isolated" obesity and obstetric complications.
AB  - OBJECTIVE: To investigate pregnancy outcomes, particularly cesarean delivery
      (CD), among women with "isolated" obesity (i.e. without additional
      comorbidities). STUDY DESIGN: We conducted a retrospective population-based study
      between the years 1988-2010. The pregnancy outcomes of obese (prepregnancy BMI
      >=30 kg/m(2)) and nonobese patients were compared. Patients with chronic
      hypertension, pregestational diabetes mellitus, other preexisting chronic
      morbidities, multiple gestations, age above 40 years, grand multiparity (above 5
      deliveries), lack of prenatal care, and following fertility treatments were
      excluded from the analysis. Stratified analyses, using multiple logistic
      regression models, were performed to control for confounders. RESULTS: During the
      study period, a total of 173,628 deliveries met the inclusion criteria; 1605
      (0.9%) occurred in patients with "isolated" obesity. Higher rates of CD were
      found among patients with "isolated" obesity (30.7% vs. 12.3%; odds ration [OR] =
      3.2; p < 0.001). When controlling for possible confounders, using a multivariable
      model with CD as the outcome variable, the association between "isolated" obesity
      and CD remained significant (adjusted OR = 2.6; p < 0.001). No significant
      differences were found in the risks of perinatal complications including
      perinatal mortality, shoulder dystocia, congenital malformations, and low 5-min
      Apgar score. CONCLUSION: "Isolated" obesity, although not a risk factor for
      adverse perinatal outcomes, is an independent risk factor for CD.

PMID- 22873477
TI  - Accurate, inaccurate and omitted details in collective emotional memories: the
      case of Itzhak Rabin's assassination.
AB  - Collective memory of the assassination of the former Israeli Prime Minister,
      Itzhak Rabin, was originally examined by asking 61 Israeli students, about two
      weeks after the assassination (T1) and about 11 months later (T2) to fill out an
      open-ended questionnaire about the assassination. About 13 years later (T3) a new
      sample of 80 students also filled out the memory questionnaire. In T2 and T3 the
      participants also self-assessed various emotional and cognitive variables about
      their memories. All answers were segmented and categorised into accurate and
      inaccurate memories. Data analyses showed that the amounts of accurate memories
      decreased from T1 to T2 by 18 per cent, and from T2 to T3 by an additional 16 per
      cent, and were positively correlated in T2 with national importance and emotional
      reaction, and in T3 with self-assessed ability to remember events and amounts of
      visual representations. Content analysis of the most frequently memorised
      accurate, inaccurate and omitted memories showed that they displayed differential
      qualitative characteristics and that the most prevalent accurate narrative has
      varied over time. It appears that the collective memories of Rabin's
      assassination showed episodic features similar to those shown by eyewitnesses
      exposed to emotion-arousing events only once. The data suggest a distinction
      between episodic "collective memories" and semantic "collective knowledge".

PMID- 22873478
TI  - Associations between socioeconomic status and allostatic load: effects of
      neighborhood poverty and tests of mediating pathways.
AB  - OBJECTIVES: We examined relationships between neighborhood poverty and allostatic
      load in a low- to moderate-income multiracial urban community. We tested the
      hypothesis that neighborhood poverty is associated with allostatic load,
      controlling for household poverty. We also examined the hypotheses that this
      association was mediated by psychosocial stress and health-related behaviors.
      METHODS: We conducted multilevel analyses using cross-sectional data from a
      probability sample survey in Detroit, Michigan (n = 919) and the 2000 US Census.
      The outcome measure was allostatic load. Independent variables included
      neighborhood and household poverty, psychosocial stress, and health-related
      behaviors. Covariates included neighborhood and individual demographic
      characteristics. RESULTS: Neighborhood poverty was positively associated with
      allostatic load (P < .05), independent of household poverty and controlling for
      potential confounders. Relationships between neighborhood poverty were mediated
      by self-reported neighborhood environment stress but not by health-related
      behaviors. CONCLUSIONS: Neighborhood poverty is associated with wear and tear on
      physiological systems, and this relationship is mediated through psychosocial
      stress. These relationships are evident after accounting for household poverty
      levels. Efforts to promote health equity should focus on neighborhood poverty,
      associated stressful environmental conditions, and household poverty.

PMID- 22873480
TI  - Syndemic theory and HIV-related risk among young transgender women: the role of
      multiple, co-occurring health problems and social marginalization.
AB  - OBJECTIVES: We assessed whether multiple psychosocial factors are additive in
      their relationship to sexual risk behavior and self-reported HIV status (i.e.,
      can be characterized as a syndemic) among young transgender women and the
      relationship of indicators of social marginalization to psychosocial factors.
      METHODS: Participants (n = 151) were aged 15 to 24 years and lived in Chicago or
      Los Angeles. We collected data on psychosocial factors (low self-esteem,
      polysubstance use, victimization related to transgender identity, and intimate
      partner violence) and social marginalization indicators (history of commercial
      sex work, homelessness, and incarceration) through an interviewer-administered
      survey. RESULTS: Syndemic factors were positively and additively related to
      sexual risk behavior and self-reported HIV infection. In addition, our syndemic
      index was significantly related to 2 indicators of social marginalization: a
      history of sex work and previous incarceration. CONCLUSIONS: These findings
      provide evidence for a syndemic of co-occurring psychosocial and health problems
      in young transgender women, taking place in a context of social marginalization.

PMID- 22873481
TI  - Temporal trends in incidence and mortality rates for colorectal cancer by tumor
      location: 1975-2007.
AB  - OBJECTIVES: We evaluated changes in colorectal cancer (CRC) incidence and
      mortality by anatomic site to assess the possible impact of CRC screening.
      METHODS: Using data from 9 Surveillance, Epidemiology, and End Results cancer
      registries, we estimated trends in 1975-2007 CRC incidence and 1985-2007
      incidence-based mortality. We evaluated trends separately for proximal and distal
      CRC, overall and by stage, tumor site, and race. RESULTS: Between 1975 and 2007,
      323 237 adults in the study area were diagnosed with CRC. For most tumor and
      population subgroups, incidence rates increased between 1975 and 1985 and
      subsequently declined markedly. Declines were most rapid between 1999 and 2007
      and were greater for distal than proximal CRC. Declines in incidence were greater
      for White than Black adults and greatest for regional-stage disease. There was
      little difference in trends across subsites within the proximal and distal
      colorectum. Declines in incidence-based mortality mirrored those for incidence.
      CONCLUSIONS: Recent declines in CRC incidence and mortality are greater for
      distal than proximal CRC. Differing trends across populations may reflect
      variations in screening prevalence; distinct trends by tumor characteristics
      likely reflect differences in screening efficacy.

PMID- 22873484
TI  - Diagnostic accuracy of monoclonal antibody based serum immunoglobulin free light
      chain immunoassays in myeloma cast nephropathy.
AB  - BACKGROUND: The development of serum immunoassays for the measurement of
      immunoglobulin free light chains has led to a paradigm shift in the diagnosis,
      assessment and monitoring of patients with plasma cell dyscrasias. The impact of
      these immunoassays which employ polyclonal antibodies was most notable for those
      patients who were previously classified as non-secretory multiple myeloma.
      Recently new monoclonal antibody based assays have become available. The purpose
      of this study was to compare the diagnostic sensitivity of these new assays with
      those already in clinical practice. METHODS: Sera from 30 patients who present
      with severe acute kidney injury and multiple myeloma were identified for
      analysis. A head to head comparison of the two commercially available free light
      chains assays was then undertaken to determine if their diagnostic sensitivity
      and specificity were comparable. RESULTS: In this first assessment of the utility
      of these new assays, we found that one of 17 patients with a lambda monoclonal
      free light chain resulting in acute kidney injury were not identified and a
      further 12% of patients were wrongly classified as having levels below those
      associated with disease specific acute kidney injury. CONCLUSION: These results
      suggest that caution should be applied to the use of new free light chain assays
      in the assessment of patients with a monoclonal gammopathy.

PMID- 22873479
TI  - Socioeconomic status and adolescent mental disorders.
AB  - OBJECTIVES: Although previous research has shown that low socioeconomic status
      (SES) is associated with mental illness, it is unclear which aspects of SES are
      most important. We investigated this issue by examining associations between 5
      aspects of SES and adolescent mental disorders. METHODS: Data came from a
      national survey of US adolescents (n = 6483). Associations among absolute SES
      (parental income and education), relative SES (relative deprivation, subjective
      social status), and community level income variation (Gini coefficient) with past
      year mental disorders were examined. RESULTS: Subjective social status (mean 0,
      variance 1) was most consistently associated with mental disorder. Odds ratios
      with mood, anxiety, substance, and behavior disorders after controlling for other
      SES indicators were all statistically significant and in the range of 0.7 to 0.8.
      Associations were strongest for White adolescents. Parent education was
      associated with low risk for anxiety disorder, relative deprivation with high
      risk for mood disorder, and the other 2 indicators were associated with none of
      the disorders considered. CONCLUSIONS: Associations between SES and adolescent
      mental disorders are most directly the result of perceived social status, an
      aspect of SES that might be more amenable to interventions than objective aspects
      of SES.

PMID- 22873485
TI  - Two new euglobals from the leaves of Eucalyptus robusta.
AB  - Two new euglobals, R1 (1) and R2 (2), together with eight known euglobals (3-10)
      were isolated from the leaves of Eucalyptus robusta. Their structures were
      established by means of spectroscopic analysis and single-crystal X-ray
      diffraction. Euglobal R1 (1) represents a new skeleton of formyl-isovaleryl
      phloroglucinol-coupled beta-phellandrene.

PMID- 22873486
TI  - CCS52A2/FZR1, a cell cycle regulator, is an essential factor for shoot apical
      meristem maintenance in Arabidopsis thaliana.
AB  - BACKGROUND: Cell division and cell fate decisions regulate organ formation and
      function in plant growth and development. It is still unclear how specific
      meristematic regulatory networks operate with the cell cycle machinery to
      translate stem cell identity and maintenance into cellular behavior. In this
      study, we address these questions by analysis of a shoot apex defective mutant,
      namely xcm9. RESULTS: Phenotypic analysis of the xcm9 mutant reveals concomitant
      premature termination of floral shoots with frequent bifurcation of the shoot
      apices, stems, and flowers. Microscopic observations show irregular cell
      organization in shoot apical meristems of xcm9. Positional cloning revealed that
      xcm9 is a loss of function allele of the CCS52A2/FZR1 gene, which has previously
      been implicated in root development. Expression analysis demonstrated that
      CCS52A2 maintains a higher transcriptional expression level in actively dividing
      tissue. Genetic studies indicated that the CCS52A2 gene functions together with
      WUSCHEL (WUS) and CLAVATA3 (CLV3) in regulating the development of the shoot
      meristem, and also contributes to this regulation together with the chromatin
      remodeling pathway. In addition, fewer xcm9 cells express CYCLIN B1:1, showing
      that cell cycle progression is disrupted in the mutant. CONCLUSION: We propose
      that the CCS52A2 gene is a mediator that functions together with meristematic
      genes to regulate meristem organization, and cross-functions with chromatin
      regulators in cell cycle progression during shoot apical meristem development.

PMID- 22873487
TI  - Population-based study on the prevalence of and risk factors for human
      papillomavirus infection in Qujing of Yunnan province, Southwest China.
AB  - BACKGROUND: Human papillomavirus (HPV) infection causes cervical cancer and
      premalignant lesions of the cervix. Prevalence of HPV infection and HPV genotypes
      vary among different regions. However there is no data on the prevalence of HPV
      infection and HPV genotypes from southwest China. This study was undertaken to
      determine the prevalence of and risk factors for HR-HPV infection in Qujing of
      Yunnan province, southwest China to provide comprehensive baseline data for
      future screening strategies. METHODS: A sample of 5936 women was chosen by the
      multi-stage stratified cluster sampling method with selection probabilities
      proportional to size (PPS). An epidemiological questionnaire was conducted via a
      face-to-face interview and cervical specimens were taken for HPV DNA testing by
      Digene Hybrid Capture 2 (HC2) test. HPV Genotyping Reverse Hybridization Test was
      used for HPV genotyping. Proportions were compared by Chi-squared tests, and
      logistic regression was utilized to evaluate risk factors. RESULTS: The median
      age was 38 years and the inter-quartile range was from 31 years to 47 years.
      97.3% of the study population was Han nationality. Overall prevalence of HR-HPV
      infection was 8.3% (494/5936) and bimodal age distribution of HPV infection was
      observed. The five most prevalent HR-HPV genotypes were HPV-16(3.4%), HPV
      56(1.7%), HPV-58(1.4%), HPV-33(1.2%) and HPV-52(0.88%). Multiple HPV infections
      were identified in 50.5% (208/412) of the positive genotyping specimens.
      Multivariate logistic regression model indicated that parity (OR = 1.35, 95% CI:
      1.18-1.53, p < 0.0001) was a risk factor for HR-HPV infection, and age of 50-65
      years (OR = 0.60, 95% CI: 0.45-0.80, p = 0.0005), being married or in stable
      relationship (OR = 0.55, 95% CI: 0.31-0.96, p = 0.035) were protective factors.
      CONCLUSIONS: This study provided baseline data on HR-HPV prevalence in the
      general female population in Qujing of Yunnan province, southwest China. The
      finding of multiple HPV infections and bimodal age distribution revealed that HPV
      screening is necessary for perimenopausal women in future.

PMID- 22873488
TI  - Two-carbon metabolites, polyphenols and vitamins influence yeast chronological
      life span in winemaking conditions.
AB  - BACKGROUND: Viability in a non dividing state is referred to as chronological
      life span (CLS). Most grape juice fermentation happens when Saccharomyces
      cerevisiae yeast cells have stopped dividing; therefore, CLS is an important
      factor toward winemaking success. RESULTS: We have studied both the physical and
      chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum
      wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an
      important negative role in aging under winemaking conditions, but additional
      metabolites produced by fermentative metabolism, such as acetaldehyde and
      acetate, have also a strong impact on longevity. Grape polyphenols quercetin and
      resveratrol have negative impacts on CLS under winemaking conditions, an
      unexpected behavior for these potential anti-oxidants. We observed that quercetin
      inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol
      performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic
      acid and nicotinamide are precursors of NAD+, and their addition reduces mean
      longevity during fermentation, suggesting a metabolic unbalance negative for CLS.
      Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and
      enhances cell lysis, while amino acids increase life span. CONCLUSIONS: Wine S.
      cerevisiae strains are able to sense changes in the environmental conditions and
      adapt their longevity to them. Yeast death is influenced by the conditions
      present at the end of wine fermentation, particularly by the concentration of two
      carbon metabolites produced by the fermentative metabolism, such as ethanol,
      acetic acid and acetaldehyde, and also by the grape juice composition,
      particularly its vitamin content.

PMID- 22873490
TI  - pi-Extended thiadiazoles fused with thienopyrrole or indole moieties: synthesis,
      structures, and properties.
AB  - We report the syntheses, structures, photophysical properties, and redox
      characteristics of donor-acceptor-fused pi-systems, namely pi-extended
      thiadiazoles 1-5 fused with thienopyrrole or indole moieties. They were
      synthesized by the Stille coupling reactions followed by the PPh(3)-mediated
      reductive cyclizations as key steps. X-Ray crystallographic studies showed that
      isomeric 1b and 2b form significantly different packing from each other, and 1a
      and 4a afford supramolecular networks via multiple hydrogen bonding with water
      molecules. Thienopyrrole-fused compounds 1b and 2b displayed bathochromically
      shifted intramolecular charge-transfer (CT) bands and low oxidation potentials as
      compared to indole-fused analog 3b and showed moderate to good fluorescence
      quantum yields (Phi(f)) up to 0.73. In 3b-5b, the introduction of electron
      donating substituents in the indole moieties substantially shifts the
      intramolecular CT absorption maxima bathochromically and leads to the elevation
      of the HOMO levels. The Phi(f) values of 3-5 (0.04-0.50) were found to be
      significantly dependent on the substituents in the indole moieties. The OFET
      properties with 1b and 2b as an active layer were also disclosed.

PMID- 22873489
TI  - DEXA measures of body fat percentage and acute phase proteins among breast cancer
      survivors: a cross-sectional analysis.
AB  - BACKGROUND: C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases
      with systemic inflammation and are related to worse survival for breast cancer
      survivors. This study examines the association between percent body fat and SAA
      and CRP and the potential interaction with NSAID use and weight change. METHODS:
      Participants included 134 non-Hispanic white and Hispanic breast cancer survivors
      from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage,
      measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of
      CRP and SAA were obtained 30 months after breast cancer diagnosis. RESULTS:
      Circulating concentrations of CRP and SAA were associated with increased
      adiposity as measured by DEXA after adjustment for age at 24-months,
      race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors
      with higher body fat >=35% had significantly higher concentrations of CRP (2.01
      mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body
      fat < 35%). Women who had gained more than 5% of their body weight since breast
      cancer diagnosis had non-statistically significant higher geometric mean levels
      of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were
      non-users of NSAIDs compared to current users; the association with SAA reached
      statistical significance (Mean SAA = 7.24, 95%CI 6.13-8.56 for non-NSAID; vs.
      4.87; 95%CI 3.95-6.0 for NSAID users respectively). CONCLUSIONS: Breast cancer
      survivors with higher body fat had higher mean concentrations of CRP and SAA than
      women with lower body fat. Further assessment of NSAID use and weight control in
      reducing circulating inflammatory markers among survivors may be worthwhile to
      investigate in randomized intervention trials as higher inflammatory markers are
      associated with worse survival.

PMID- 22873492
TI  - Cutaneous adverse reactions to amoxicillin-clavulanic acid suspension in
      children: the role of sodium benzoate.
AB  - BACKGROUND: In Europe amoxicillin plus clavulanic acid is the most commonly
      prescribed antibiotic and sodium benzoate is contained in the suspension
      formulation as a preservative. OBJECTIVE: We studied the relevance of sodium
      benzoate as the culprit agent. In a group of children with a history of adverse
      reactions to amoxicillin plus clavulanic acid suspension. STUDY DESIGN: A total
      of 89 children were enrolled over a period of 3 years (2006 - 2009). Single blind
      oral provocation tests (OPTs) with amoxicillin plus clavulanic acid, sodium
      benzoate and placebo were performed. 20 children with recurrent idiopathic
      urticaria were investigated as a control group. RESULTS: according to personal
      history: 70% of reactions were late in developing while 23% of reactions were
      immediate and for 5% of the cases it was not possible to define the timing. 8
      children (8/89=9%) resulted positive to the provocation tests with amoxicillin
      plus clavulanic acid; ten children (10/89=11%) had positive results with sodium
      benzoate; 3% had a double positivity (i.e. excipient and active drug). The timing
      of reactions significantly differs between the Amoxicillin plus clavulanic acid
      and sodium benzoate groups (p=0.002). CONCLUSION: Sodium benzoate probably acts
      through a non-immunologic mechanism and care should be given to children allergic
      to sodium benzoate containing pharmaceutical formulations.

PMID- 22873491
TI  - Effect of anticholinergic use for the treatment of overactive bladder on
      cognitive function in postmenopausal women.
AB  - BACKGROUND: Overactive bladder (OAB) is a common condition affecting the elderly.
      The mainstay of treatment for OAB is medical therapy with anticholinergics.
      However, adverse events have been reported with this class of drugs, including
      cognitive changes. OBJECTIVE: The objective of this study was to investigate the
      effect of an anticholinergic medication, trospium chloride, on cognitive function
      in postmenopausal women being treated for OAB. METHODS: This was a prospective
      cohort study conducted at a urogynaecology clinic at one academic medical centre
      from January to December 2010, with 12-week follow-up after medication
      initiation. Women aged 55 years or older seeking treatment for OAB and opting for
      anticholinergic therapy were recruited. Baseline cognitive function was assessed
      via the Hopkins Verbal Learning Test-Revised Form (HVLT-R) [and its five
      subscales], the Orientation, Memory & Concentration (OMC) short form, and the
      Mini-Cog evaluation. After initiation of trospium chloride extended release,
      cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder
      function was assessed via three condition-specific quality-of-life
      questionnaires. Secondary outcomes included change in bladder symptoms,
      correlation between cognitive and bladder symptoms, and overall medication
      compliance. The main outcome measure was change in HVLT-R score at Week 4 after
      medication initiation, compared with baseline (pre-medication) score. RESULTS: Of
      50 women enrolled, 35 completed the assessment. The average age was 70.4 years
      and 77.1% had previously taken anticholinergic medication for OAB. At enrollment
      65.7% had severe overactive bladder and 71.4% had severe urge incontinence.
      Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p =
      0.037), HVLT-R Delayed Recognition subscale (p = 0.011) and HVLT-R Recognition
      Bias subscale (p = 0.01). At Week 1 the HVLT-R Learning subscale declined from
      baseline (p = 0.029). All HVLT-R scores normalized by Week 4. OMC remained stable
      throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did
      not improve until Week 4, based on questionnaire scores (p < 0.05). CONCLUSION:
      Cognitive function exhibited early changes after initiation of trospium chloride
      but normalized within 4 weeks. Cognitive changes occurred weeks prior to OAB
      symptom improvement. Surveillance for cognitive changes with anticholinergic use
      should be part of OAB management.

PMID- 22873493
TI  - Safety of cabergoline in the management of pituitary prolactin-induced symptoms
      with patients treated with atypical neuroleptics.
AB  - Atypical antipsychotic-induced hyperprolactinemia can cause important clinical
      symptoms, particularly in young women and also in men, such as impotence, loss of
      libido, gynecomastia, anovulation and galactorrhea. METHODS: Observational over
      one-year follow-up of six patients (four women and two men, mean age of 31.1
      years, range 26-37), treated with different atypical antipsychotics in an
      outpatient psychiatric device, who had clinical complications associated to high
      prolactin serum levels. All of them were treated with standard doses of
      cabergoline. RESULTS: Most patients experienced significant clinical improvement
      after treatment with standard doses of cabergoline (mean dosage 1.08 mg/week),
      maintained for a mean of 18 month. Normal prolactin levels were achieved after
      the first months of treatment with cabergoline. No side effects or worsening of
      psychotic or behavioral symptoms were observed. CONCLUSIONS: Long-term treatment
      with cabergoline seems to be safe in atypical antipsychotic-treated patients.

PMID- 22873494
TI  - Ticlopidine safety profile: a case/non-case study on the basis of the spontaneous
      ADRs reporting in Italy.
AB  - INTRODUCTON: Ticlopidine is an antiplatelet agent available from several decades.
      Its most important adverse drug reactions (ADRs) involve haematological system.
      Our aim was to evaluate the safety profile of ticlopidine in the real life, on
      the basis of spontaneous ADR reporting. MATERIALS AND METHODS: Spontaneous
      reports from 8 Italian Regions collected from 1990 to March 2007 were analysed.
      According to WHO Adverse Reaction Terminology for causality assessment only
      "certain", "probable" or "possible" ADRs were included. Association between drugs
      and any ADR was assessed by using the case/non-case methodoloy. Reporting odds
      ratio (ROR) was computed as a measure of disproportionality. RESULTS: Overall,
      478 reports concerning ticlopidine were analysed. The system organ classes with
      significant disproportionality for ticlopidine included White Cell Disorders
      (ROR=22.43, 95% CI 18.54-27.12), Red Cell Disorders (8.22; 6.03-11.18), Liver And
      Biliary System (6.67; 5.35-8.32), Platelet, Bleeding & Clotting (6.59; 5.16
      8.40). Fifteen percent of the ADRs occurred beyond the first three months of
      ticlopidine therapy. In 386 reports (80.7%), ticlopidine was the only suspected
      drug. CONCLUSION: Safety profile of ticlopidine can be considered well
      established in terms of ADRs type but their frequency and severity continue to be
      higher in its current use. Since this drug is still widely used in Italy, both
      healthcare providers and patients should be aware of its ADRs. More specifically,
      patients should be regularly monitored during the whole period of use and not
      only in the first months of treatment.

PMID- 22873496
TI  - Use of complementary medicine amongst patients on antiretroviral drugs in an HIV
      treatment centre in Lagos, Nigeria.
AB  - Traditional herbal remedies have been used to treat many ailments in Nigeria but
      the safety of herbal remedies has been the major concerns to many people
      especially when the chemical constituents of the products are not known. This
      study is therefore designed to evaluate the prevalence of use of complementary
      drugs with antiretroviral (ARV) therapy and possible treatment outcome of the
      concurrent utilization of these therapeutic agents. A descriptive cross-sectional
      survey of 354 HIV patients attending APIN clinics in LUTH using a consecutive
      sampling technique was used. There was also correlation of the data obtained from
      the patients with their clinical case notes. Results showed that only 8.2 % of
      the respondents' used herbal medicine concurrently with ARV therapy. Ninety
      percent of the participants were on a two nucleoside and one non-nucleoside based
      ARV therapy. The most common regimen (55%) was Zidovudine/lamivudine/Nevirapine
      fixed dose combination while 10% use a protease inhibitor based regimen. The
      commonly herbal drugs used ranges from Jobelyn [Sorghum bicolor plant leaves
      (13.8%)], Garlic [Allicin, gamma-glutamyl- (s)-ally-L-Cysteine] (10.3%), Ginger
      [Essential oil] (17.2%) and Aloe vera [Hydroxyanthracene derivatives expressed as
      Barbaloin] (10.3%). The major reason for the commencement of herbal medicine is
      the perception that the medicine will boost their immunity (65.5%). However,
      there was a marginal improvement though not significant (p >= 0.05) in the CD4
      counts (489.8 +/- 195.2; 419.1 +/- 236.2) and viral load (5117.8 +/- 26092.0;
      31136.7 +/- 197954.6) of HIV patients on herbal drugs compared to those who are
      not on herbal drugs. Herbal medicines have potentials to interact with ARVs and
      thus result in adverse reactions and possibly therapeutic failure. There is need
      for thorough investigation of the pharmacological action of these herbal
      medicines in HIV treatment taking into consideration their pharmacokinetic and
      toxicological profile.

PMID- 22873495
TI  - Ketamine induces toxicity in human neurons differentiated from embryonic stem
      cells via mitochondrial apoptosis pathway.
AB  - Ketamine is widely used for anesthesia in pediatric patients. Growing evidence
      indicates that ketamine causes neurotoxicity in a variety of developing animal
      models. Our understanding of anesthesia neurotoxicity in humans is currently
      limited by difficulties in obtaining neurons and performing developmental
      toxicity studies in fetal and pediatric populations. It may be possible to
      overcome these challenges by obtaining neurons from human embryonic stem cells
      (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into
      every cell type. In this study, we investigated the toxic effect of ketamine on
      neurons differentiated from hESCs. Two-week-old neurons were treated with
      different doses and durations of ketamine with or without the reactive oxygen
      species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial
      membrane potential (DeltaPsim), cytochrome c distribution within cells,
      apoptosis, and ROS production were evaluated. Here we show that ketamine induced
      ultrastructural abnormalities and dose- and time-dependently caused cell death.
      In addition, ketamine decreased DeltaPsim and increased cytochrome c release from
      mitochondria. Ketamine also increased ROS production and induced differential
      expression of oxidative stress-related genes. Specifically, abnormal
      ultrastructural and DeltaPsim changes occurred earlier than cell death in the
      ketamine-induced toxicity process. Furthermore, Trolox significantly decreased
      ROS generation and attenuated cell death caused by ketamine in a dose-dependent
      manner. In conclusion, this study illustrates that ketamine time- and dose
      dependently induces human neurotoxicity at supraclinical concentrations via ROS
      mediated mitochondrial apoptosis pathway and that these side effects can be
      prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might
      provide a promising tool for studying anesthetic-induced developmental
      neurotoxicity and prevention strategies.

PMID- 22873497
TI  - Effects of anesthetics on mitochondrial signaling and function.
AB  - Mitochondria are considered the powerhouses of the cell playing an important role
      in energy metabolism. However, they are highly vulnerable to inhibition or
      uncoupling of the energy harnessing process and run a high risk of causing
      catastrophic damage to the cell. Several anesthetics or drugs commonly given
      during anesthesia interact with mitochondria and affect their structure or impair
      respiratory chain functioning with decreased ATP production. Mitochondria, in
      fact, are a potential site of action of general and local anesthetics. The
      purpose of this review is to update present knowledge and describe the effects
      and molecular mechanisms of the action of the most used drugs of anesthesia on
      mitochondria.

PMID- 22873498
TI  - Exploratory and regulatory assessments on photosafety of new drug entities.
AB  - Drug-induced phototoxicity is elicited after exposure of the skin and/or eyes to
      topically or systemically administered pharmaceutical substances, followed by
      exposure to sunlight. This undesirable side effect is one of the impediments in
      drug discovery and development, and substantial efforts have been made to avoid
      drug-induced phototoxic reactions. To evaluate the phototoxic potential of
      compounds, effective methodologies have been developed over the past few years,
      and screening strategies have also been proposed for predicting in vivo
      phototoxic reactions. European and American regulatory agencies have published
      guidelines for predicting and avoiding drug-induced phototoxicity in an early
      phase of drug discovery. The guidelines have indicated the requirements for
      assessing the photosafety of chemicals on the basis of their photochemical
      behaviors and have recommended some phototoxic assessment tools for aiding new
      drug development. A number of phototoxic screening systems have also been
      proposed on the basis of the pathogenesis of drug-induced phototoxicity, and some
      of them have already been applied to the phototoxic evaluation of new drug
      entities in drug discovery and development. The present review aims to summarize
      the current status of research tools, screening strategy and regulations for
      evaluating the photosafety of new drug candidates and to introduce our thoughts
      on the phototoxic risk assessments of compounds.

PMID- 22873499
TI  - Update on the cardiac safety of moxifloxacin.
AB  - Cardiac safety was compared in patients receiving moxifloxacin and other
      antimicrobials in a large patient population from Phase II-IV randomized active
      controlled clinical trials. Moxifloxacin 400 mg once-daily monotherapy was
      administered orally (PO) or sequentially (intravenous/oral, IV/PO). Across 64
      trials, 21,298 patients received PO therapy (10,613 moxifloxacin, 10,685
      comparators) while 6846 received sequential IV/PO therapy (3431 moxifloxacin,
      3415 comparators). Treatment-emergent cardiac adverse event (AE) rates were
      similar for moxifloxacin and comparators in PO (6.6% vs 5.8%) and IV/PO (11.0% vs
      12.0%) trials. Treatment-emergent cardiac adverse drug reactions were rare in PO
      (moxifloxacin 3.2% vs comparators 2.4%) and IV/PO (moxifloxacin 1.4% vs
      comparators 1.5%) patients. There were five (<0.02%) treatment-emergent drug
      related deaths due to cardiac events out of 28,144 patients; one PO patient died
      treated with comparators, one patient died treated with IV/PO moxifloxacin, and
      three patients died after treatment with IV/PO comparators. Only one case of
      treatment-related non-fatal torsade de pointes occurred in the comparator arm.
      Incidence rates of cardiac AEs remained low in populations at elevated risk of
      cardiac events predisposed to QTc prolongation (i.e. community-acquired pneumonia
      patients admitted to the intensive care unit and/or mechanical ventilation,
      patients with documented prolongation of baseline QTc interval, women, and
      patients >= 65 years old). There was no evidence of unexpected cardiac events.
      After moxifloxacin treatment, an expected small prolongation in QTcB and QTcF was
      found. This analysis of numerous clinical trials shows the favorable cardiac
      safety profile of moxifloxacin, when used appropriately and according to its
      label, versus other antibiotics.

PMID- 22873500
TI  - Possibility of enhanced risk of retinal angiogenesis in athletes with pre-
      existing retinal situation abusing erythropoietin doping: a hypothesis.
AB  - Doping with erythropoietic proteins such as erythropoietin (EPO) is a serious
      issue in sport. There is little information on the possible ophthalmologic
      alterations followed by frequent EPO abuse in athletes. EPO is a potent retinal
      angiogenic factor and is capable of stimulating retinal angiogenesis and
      neovascularization in the presence of ischemia. Systemic and intravitreal EPO
      concentrations are highly correlated. A linkage between EPO doping and retinal
      proliferation is possible and further studies are warranted. Gathering and
      analyzing data on retinal findings from these athletes, either retrospectively or
      prospectively might yield preliminary information to support the safety of those
      athletes. Implications of this hypothesis cover other kinds of
      neovascularizations and angiogenesis.

PMID- 22873501
TI  - Implemented data mining and signal management systems on spontaneous reporting
      systems' databases and their availability to the scientific community - a
      systematic review.
AB  - Adverse drug reactions' spontaneous reporting systems are an important element in
      worldwide pharmacovigilance, gathering potentially useful information for post
      marketing drug safety surveillance. Data mining and signal management systems,
      providing the capability of reading and interpreting these systems' raw data
      (data that has not been subjected to processing or any other manipulation),
      improve its analysis process. In order for this analysis to be possible, both
      data mining and signal management systems and raw data should be available to
      researchers and the scientific community. The purpose of this work was to provide
      an overview of the spontaneous reporting systems databases reported in literature
      as having implemented a data mining and signal management system and the
      implementation itself, evidencing their availability to researchers. A systematic
      review was carried out, concluding that they are freely provided to researchers
      within institutions responsible for maintaining the spontaneous reporting
      systems, but not to most researchers within the scientific community.

PMID- 22873502
TI  - Hypocalcemia induced by raloxifene.
AB  - Raloxifene is an anti-resorptive agent used in postmenopausal osteoporosis. This
      is the first report of the occurrence of clinically significant hypocalcemia
      following raloxifene treatment in a patient with occult vitamin D deficiency.
      Since vitamin D deficiency is widely prevalent in the community, screening for
      vitamin D deficiency and its correction is advisable before the initiation of
      anti-resorptive therapy.

PMID- 22873503
TI  - Oxaliplatin-induced lung toxicity. Case report and review of the literature.
AB  - Rapidly developing pulmonary fibrosis associated with the use of the anti-cancer
      drug oxaliplatin has been reported mainly by Asiatic literature as isolate case
      reports. This rare but potentially fatal side effect has neither identified risk
      factors nor established treatment guideline. We report here a new clinical case
      concerning a patient with advanced gastric cancer treated with the oxaliplatin
      based FOLFOX regimen along with a review of the literature as well as a
      discussion of emerging experimental treatment mainly based on imatinib.

PMID- 22873504
TI  - Moxifloxacin-induced hypoglycemia in a non-diabetic patient.
AB  - Hypoglycemia is a rare life threatening adverse drug reaction associated with
      various fluoroquinolones like ciprofloxacin, gatifloxacin and levofloxacin.
      Moxifloxacin was considered safe in this regard. Only one case has been reported
      for moxifloxacin-induced hypoglycemia in a renal failure patient. Here, we are
      reporting the second case of hypoglycemia due to moxifloxacin without any major
      co-morbid condition.

PMID- 22873507
TI  - NIH Austerity?

PMID- 22873505
TI  - Glatiramer acetate induced hepatotoxicity.
AB  - INTRODUCTION: Glatiramer acetate (Copaxone), a polypeptide has been approved for
      treating patients with active relapsing-remitting multiple sclerosis. CASE
      PRESENTATION: We report the first case of severe acute hepatitis after commencing
      treatment for multiple sclerosis with glatiramer acetate. A 31-year-old female
      with multiple sclerosis presented with anorexia, lethargy and jaundice five weeks
      after commencing glatiramer acetate. She had never received beta-interferon
      treatment. Investigations revealed a bilirubin of 0.109 mmol/L (0.002-0.02
      mmoL/L) and prothrombin time of 21 secs (9-15 secs). Her liver function tests
      were normal before commencing glatiramer acetate. A liver biopsy performed
      approximately 6 weeks after commencement of glatiramer acetate showed
      predominantly centrilobular hepatocyte necrosis with portal-venous bridging,
      along with mild portal and interface hepatitis. The necrosis was not accompanied
      by an acute inflammatory or chronic inflammatory infiltrate. The features were
      not suggestive of autoimmune hepatitis but consistent with drug toxicity. The
      liver tests returned to normal within 2 months after cessation of glatiramer
      acetate. CONCLUSION: Physicians should be aware that glatiramer acetate can be
      associated with uncommon but yet significantly severe liver toxicity.

PMID- 22873510
TI  - A scientist and an advocate. An interview with Steven Salzberg by Kristie Nybo.

PMID- 22873512
TI  - Tearing the top off 'Top-Down' Proteomics.

PMID- 22873513
TI  - Retroviral transfection.

PMID- 22873516
TI  - Executive function and emotional focus in autobiographical memory specificity in
      older adults.
AB  - The current study examined the role of executive function in retrieval of
      specific autobiographical memories in older adults with regard to control of
      emotion during retrieval. Older and younger adults retrieved memories of specific
      events in response to emotionally positive, negative and neutral word cues.
      Contributions of inhibitory and updating elements of executive function to
      variance in autobiographical specificity were assessed to determine processes
      involved in the commonly found age-related reduction in specificity. A negative
      relationship between age and specificity was only found in retrieval to neutral
      cues. Alternative explanations of this age preservation of specificity of
      emotional recall are explored, within the context of control of emotion in the
      self-memory system and preserved emotional processing and positivity effect in
      older adults. The pattern of relationships suggests updating, rather than
      inhibition, as the source of age-related reduction in specificity, but that
      emotional processing (particularly of positively valenced memories) is not
      influenced by age-related variance in executive control. The tendency of older
      adults to focus on positive material may thus act as a buffer against detrimental
      effects of reduced executive function capacity on autobiographical retrieval,
      representing a possible target for interventions to improve specificity of
      autobiographical memory retrieval in older adults.

PMID- 22873515
TI  - Structure and function of assemblages of Bacteria and Archaea in model anaerobic
      aquifer columns: can functional instability be practically beneficial?
AB  - Biodegradable organic carbon is often added to aquifers to stimulate microbial
      reduction of oxidized contaminants. This carbon also stimulates fermenters, which
      generate important metabolites that can fuel contaminant reduction and may
      enhance dissolution of hydrophobic compounds. Therefore, understanding how
      different methods of carbon addition affect the fermentative community will
      enable design of more effective remediation strategies. Our research objective
      was to evaluate the microbial communities that developed in model aquifer columns
      in response to pulsed or continuous molasses input. Results indicated that the
      continuously fed column produced relatively low concentrations of metabolic
      intermediates and had a greater proportion of Bacteria and methanogens, as
      measured by quantitative polymerase chain reaction, near the column inlet. In
      contrast, the pulsed-fed column generated periodic high concentrations of
      metabolic intermediates, with Bacteria and methanogens distributed throughout the
      length of the column. The community structures of Bacteria and Archaea, measured
      via automated ribosomal intergenic spacer analysis, in the pulsed-fed column were
      significantly different from those in the control column (not fed). The microbial
      community composition of the continuously fed column, however, became
      increasingly similar to the control column along the column length. These results
      demonstrate that a strategy of pulsed carbon addition leads to activity that is
      associated with functional instability, in terms of the production of periodic
      pulses of fermentation products and changing carbon concentration, and may be
      advantageous for remediation by producing large quantities of beneficial
      intermediates and resulting in more homogenously distributed biomass.

PMID- 22873517
TI  - Microwave synthesis and thermal properties of polyacrylate derivatives containing
      itaconic anhydride moieties.
AB  - BACKGROUND: Microwave irradiation as an alternative heat source is now a well
      known method in synthetic chemistry. Microwave heating has emerged as a powerful
      technique to promote a variety of chemical reactions, offering reduced pollution,
      low cost and offer high yields together with simplicity in processing and
      handling. On the other hand, copolymers containing both hydrophilic and
      hydrophobic segments are drawing considerable attention because of their possible
      use in biological systems. Various copolymer compositions can produce a very
      large number of different arrangements, producing materials of varying chemical
      and physical properties. Thus, the hydrophilicity of copolymers can be modified
      by changing the amount of incorporated itaconic anhydride. RESULTS: A series of
      methyl methacrylate (MMA) and acrylamide (AA) copolymers containing itaconic
      anhydride (ITA) were synthesized by microwave irradiation employing a multimode
      reactor (Synthos 3000 Aton Paar, GmbH, 1400 W maximum magnetron) as well as
      conventional method. The thermal properties of the copolymers were evaluated by
      different techniques. Structure-thermal property correlation based on changing
      the itaconic anhydride ratio was demonstrated. Results revealed that the
      incorporation of itaconic anhydride into the polymeric backbone of all series
      affect the thermal stability of copolymers. In addition, the use of the microwave
      method offers high molecular weight copolymers which lead eventually to an
      increase in thermal stability. CONCLUSIONS: Microwave irradiation method showed
      advantages for the produced copolymers compared to that prepared by conventional
      method, where it can offer a copolymer in short time, high yield, more pure
      compounds and more thermally stable copolymers, rather than conventional method.
      Also, microwave irradiation method gives higher molecular weight due to
      prevention of the chain transfer. Moreover, as the itaconic anhydride content
      increases the thermal stability and Tg increase due to the decrease in the
      crystallinity.

PMID- 22873518
TI  - Ultrasound-indicated cerclage: Shirodkar vs. McDonald.
AB  - OBJECTIVE: To compare the efficacy of Shirodkar to McDonald cerclage in patients
      with singleton pregnancies undergoing an ultrasound-indicated cerclage. METHODS:
      Historical cohort of all patients with singleton pregnancies undergoing cerclage
      for the indication of a short cervix on ultrasound (ultrasound indicated) at one
      institution in 2005-2010. We compared outcomes based on cerclage type, Shirodkar
      or McDonald. Outcome measures were gestational age (GA) at delivery, delivery
      >=35 weeks, >=32 weeks, and PPROM. Multivariable regression analysis was
      performed to control for significant variables. RESULTS: Seventy-four patients
      with singleton pregnancies underwent an ultrasound-indicated cerclage in the
      study period (47 Shirodkar, 27 McDonald). Shirodkar was associated with later GA
      at delivery (mean GA at delivery 36.98 +/- 3.39 vs. 33.34 +/- 6.37 weeks, p =
      0.006), a higher likelihood of delivering >=35 weeks (83 vs. 55.6%, p = 0.011)
      and >=32 weeks (91.5 vs. 59.3%, p = 0.001), and a lower likelihood of preterm
      premature rupture of membrane (PPROM) (13.0 vs. 46.2%, p = 0.002). On adjusted
      analysis controlling for differing baseline characteristics, Shirodkar remained
      significantly associated with an increased incidence of delivery >=32 weeks (odds
      ratio [OR]: 5.180, 95% CI: 1.024-26.205). CONCLUSION: Compared to the McDonald
      technique, the Shirodkar technique was more effective in prolonging pregnancy in
      patients with singleton pregnancies undergoing ultrasound-indicated cerclage. A
      prospective trial is needed to compare these two techniques.

PMID- 22873519
TI  - Preface. Journal of Biological Dynamics.

PMID- 22873520
TI  - A discrete stage-structured two-species competition model with sexual and clonal
      reproduction.
AB  - In this paper, we analyse a discrete stage-structured model which is a
      generalization of the two-species competition model studied in [2]. Motivated by
      plant populations, each species is assumed to reproduce both sexually and
      clonally. We show that this model has a dynamical behaviour that is similar to
      that of the classical continuous two-dimensional Lotka-Volterra model under weak
      nonlinearities of the Beverton-Holt type. By allowing the species to have
      different competition efficiencies, we show that it is possible to obtain
      different dynamics including coexistence, bistability and competitive exclusion,
      in contrast with the model studied in [2], which exhibits only competitive
      exclusion behaviour.

PMID- 22873522
TI  - Cannibalism in discrete-time predator-prey systems.
AB  - In this study, we propose and investigate a two-stage population model with
      cannibalism. It is shown that cannibalism can destabilize and lower the magnitude
      of the interior steady state. However, it is proved that cannibalism has no
      effect on the persistence of the population. Based on this model, we study two
      systems of predator-prey interactions where the prey population is cannibalistic.
      A sufficient condition based on the nontrivial boundary steady state for which
      both populations can coexist is derived. It is found via numerical simulations
      that introduction of the predator population may either stabilize or destabilize
      the prey dynamics, depending on cannibalism coefficients and other vital
      parameters.

PMID- 22873521
TI  - Coping behaviour as an adaptation to stress: post-disturbance preening in
      colonial seabirds.
AB  - In humans, coping behaviour is an action taken to soothe oneself during or after
      a stressful or threatening situation. Some human behaviours with physiological
      functions also serve as coping behaviours, for example, comfort sucking in
      infants and comfort eating in adults. In birds, the behaviour of preening, which
      has important physiological functions, has been postulated to soothe individuals
      after stressful situations. We combine two existing modelling approaches -
      logistic regression and Darwinian dynamics - to explore theoretically how a
      behaviour with crucial physiological function might evolve into a coping
      behaviour. We apply the method to preening in colonial seabirds to investigate
      whether and how preening might be co-opted as a coping behaviour in the presence
      of predators. We conduct an in-depth study of the environmental correlates of
      preening in a large gull colony in Washington, USA, and we perform an independent
      field test for comfort preening by computing the change in frequency of preening
      in gulls that were alerted to a predator, but did not flee.

PMID- 22873523
TI  - Modeling energetic and theoretical costs of thermoregulatory strategy.
AB  - Poikilothermic ectotherms have evolved behaviours that help them maintain or
      regulate their body temperature (T (b)) around a preferred or 'set point'
      temperature (T (set)). Thermoregulatory behaviors may range from body positioning
      to optimize heat gain to shuttling among preferred microhabitats to find
      appropriate environmental temperatures. We have modelled movement patterns
      between an active and non-active shuttling behaviour within a habitat (as a
      biased random walk) to investigate the potential cost of two thermoregulatory
      strategies. Generally, small-bodied ectotherms actively thermoregulate while
      large-bodied ectotherms may passively thermoconform to their environment. We were
      interested in the potential energetic cost for a large-bodied ectotherm if it
      were forced to actively thermoregulate rather than thermoconform. We therefore
      modelled movements and the resulting and comparative energetic costs in precisely
      maintaining a T (set) for a small-bodied versus large-bodied ectotherm to study
      and evaluate the thermoregulatory strategy.

PMID- 22873524
TI  - Boundaries of sustainability in simple and elaborate models of agricultural pest
      control with a pesticide and a non-toxic refuge.
AB  - In two models of pest control using a pesticidal crop along with a non-pesticidal
      refuge to prevent the development of resistance, we numerically compute the
      bifurcations that bound the region in parameter space where control is
      sustainable indefinitely. An exact formula for one of the bifurcation surfaces in
      one of the models is also found. One model is conceptual and as simple as
      possible. The other is realistic and very detailed. Despite the great differences
      in the models, we find the same distinctive bifurcation structure. We focus on
      the parameters that determine: (i) the restriction of pest exchange between the
      crop and the refuge, which we call 'screening' the refuge, and (ii) the
      recessiveness of the resistance trait. The screened refuge technique is seen to
      work in the models up to quite high values of fitness of resistant heterozygotes,
      that is, even when resistance is not strongly recessive.

PMID- 22873526
TI  - Polyaminoquinoline iron chelators for vectorization of antiproliferative agents:
      design, synthesis, and validation.
AB  - Iron chelation in tumoral cells has been reported as potentially useful during
      antitumoral treatment. Our aim was to develop new polyaminoquinoline iron
      chelators targeting tumoral cells. For this purpose, we designed, synthesized,
      and evaluated the biological activity of a new generation of iron chelators,
      which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked
      to linear polyamine vectors. These were designed to target tumor cells expressing
      an overactive polyamine transport system (PTS). A set of Quilamines bearing
      variable polyamine chains was designed and assessed for their ability to interact
      with iron. Quilamines were also screened for their cytostatic/cytotoxic effects
      and their selective uptake by the PTS in the CHO cell line. Our results show that
      both the 8-HQ moiety and the polyamine part participate in the iron coordination.
      HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety
      and was shown to be highly taken up by the PTS and to display an efficient
      antiproliferative activity that occurred in the micromolar range. In addition,
      cytotoxicity was only observed at concentrations higher than 100 MUM. We also
      demonstrated the high complexation capacity of HQ1-44 with iron while much weaker
      complexes were formed with other cations, indicative of a high selectivity. We
      applied the density functional theory to study the binding energy and the
      electronic structure of prototypical iron(III)-Quilamine complexes. On the basis
      of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for
      iron(III) especially in the form of a 1:2 complex.

PMID- 22873525
TI  - A single proteolytic cleavage within the lower hinge of trastuzumab reduces
      immune effector function and in vivo efficacy.
AB  - INTRODUCTION: Recent studies reported that human IgG antibodies are susceptible
      to specific proteolytic cleavage in their lower hinge region, and the hinge
      cleavage results in a loss of Fc-mediated effector functions. Trastuzumab is a
      humanized IgG1 therapeutic monoclonal antibody for the treatment of HER2
      overexpressing breast cancers, and its mechanisms of action consist of inhibition
      of HER2 signaling and Fc-mediated antibody-dependent cellular cytotoxicity
      (ADCC). The objective of this study is to investigate the potential effect of
      proteinase hinge cleavage on the efficacy of trastuzumab using both a breast
      cancer cell culture method and an in vivo mouse xenograft tumor model. METHODS:
      Trastuzumab antibody was incubated with a panel of human matrix
      metalloproteinases, and proteolytic cleavage in the lower hinge region was
      detected using both western blotting and mass spectrometry. Single hinge cleaved
      trastuzumab (scIgG-T) was purified and evaluated for its ability to mediate ADCC
      and inhibition of breast cancer cell proliferation in vitro as well as anti-tumor
      efficacy in the mouse xenograft tumor model. Infiltrated immune cells were
      detected in tumor tissues by immunohistochemistry. RESULTS: scIgG-T retains HER2
      antigen binding activity and inhibits HER2-mediated downstream signaling and cell
      proliferation in vitro when compared with the intact trastuzumab. However, scIgG
      T lost Fc-mediated ADCC activity in vitro, and had significantly reduced anti
      tumor efficacy in a mouse xenograft tumor model. Immunohistochemistry showed
      reduced immune cell infiltration in tumor tissues treated with scIgG-T when
      compared with those treated with the intact trastuzumab, which is consistent with
      the decreased ADCC mediated by scIgG-T in vitro. CONCLUSION: Trastuzumab can be
      cleaved by matrix metalloproteinases within the lower hinge. scIgG-T exhibited a
      significantly reduced anti-tumor efficacy in vivo due to the weakened immune
      effector function such as ADCC. The results suggest that the lower hinge cleavage
      of trastuzumab can occur in the tumor microenvironment where matrix
      metalloproteinases often have high levels of expression and scIgG-T might
      compromise its anti-tumor efficacy in the clinic. However, further studies are
      needed to validate these hypotheses in the clinical setting.

PMID- 22873527
TI  - Therapeutics for filovirus infection: traditional approaches and progress towards
      in silico drug design.
AB  - INTRODUCTION: Ebolaviruses and marburgviruses cause severe and often lethal human
      hemorrhagic fevers. As no FDA-approved therapeutics are available for these
      infections, efforts to discover new therapeutics are important, especially
      because these pathogens are considered biothreats and emerging infectious
      diseases. All methods for discovering new therapeutics should be considered,
      including compound library screening in vitro against virus and in silico
      structure-based drug design, where possible, if sufficient biochemical and
      structural information is available. AREAS COVERED: This review covers the
      structure and function of filovirus proteins, as they have been reported to date,
      as well as some of the current antiviral screening approaches. The authors
      discuss key studies mapping small-molecule modulators that were found through
      library and in silico screens to potential sites on viral proteins or host
      proteins involved in virus trafficking and pathogenesis. A description of
      ebolavirus and marburgvirus diseases and available animal models is also
      presented. EXPERT OPINION: To discover novel therapeutics with potent efficacy
      using sophisticated computational methods, more high-resolution crystal
      structures of filovirus proteins and more details about the protein functions and
      host interaction will be required. Current compound screening efforts are finding
      active antiviral compounds, but an emphasis on discovery research to investigate
      protein structures and functions enabling in silico drug design would provide
      another avenue for finding antiviral molecules. Additionally, targeting of
      protein-protein interactions may be a future avenue for drug discovery since
      disrupting catalytic sites may not be possible for all proteins.

PMID- 22873528
TI  - The ethics of early evidence--preparing for a possible breakthrough in
      Alzheimer's disease.

PMID- 22873529
TI  - Use patents, carve-outs, and incentives--a new battle in the drug-patent wars.

PMID- 22873530
TI  - Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.
AB  - BACKGROUND: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that
      is being investigated as a targeted immunomodulator and disease-modifying therapy
      for rheumatoid arthritis. METHODS: In this phase 3, double-blind, placebo
      controlled, parallel-group, 6-month study, 611 patients were randomly assigned,
      in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib
      twice daily, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or
      placebo for 3 months followed by 10 mg of tofacitinib twice daily. The primary
      end points, assessed at month 3, were the percentage of patients with at least a
      20% improvement in the American College of Rheumatology scale (ACR 20), the
      change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
      scores (which range from 0 to 3, with higher scores indicating greater
      disability), and the percentage of patients with a Disease Activity Score for 28
      joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less
      than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more
      disease activity). RESULTS: At month 3, a higher percentage of patients in the
      tofacitinib groups than in the placebo groups met the criteria for an ACR 20
      response (59.8% in the 5-mg tofacitinib group and 65.7% in the 10-mg tofacitinib
      group vs. 26.7% in the combined placebo groups, P<0.001 for both comparisons).
      The reductions from baseline in HAQ-DI scores were greater in the 5-mg and 10-mg
      tofacitinib groups than in the placebo groups (-0.50 and -0.57 points,
      respectively, vs. -0.19 points; P<0.001). The percentage of patients with a DAS28
      4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with
      placebo (5.6% and 8.7% in the 5-mg and 10-mg tofacitinib groups, respectively,
      and 4.4% with placebo; P=0.62 and P=0.10 for the two comparisons). Serious
      infections developed in six patients who were receiving tofacitinib. Common
      adverse events were headache and upper respiratory tract infection. Tofacitinib
      treatment was associated with elevations in low-density lipoprotein cholesterol
      levels and reductions in neutrophil counts. CONCLUSIONS: In patients with active
      rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in
      signs and symptoms of rheumatoid arthritis and improvement in physical function.
      (Funded by Pfizer; ORAL Solo ClinicalTrials.gov number, NCT00814307.).

PMID- 22873532
TI  - Treatment of older patients with mantle-cell lymphoma.
AB  - BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma
      is poor. Chemoimmunotherapy results in low rates of complete remission, and most
      patients have a relapse. We investigated whether a fludarabine-containing
      induction regimen improved the complete-remission rate and whether maintenance
      therapy with rituximab prolonged remission. METHODS: We randomly assigned
      patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who
      were not eligible for high-dose therapy to six cycles of rituximab, fludarabine,
      and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21
      days. Patients who had a response underwent a second randomization to maintenance
      therapy with rituximab or interferon alfa, each given until progression. RESULTS:
      Of the 560 patients enrolled, 532 were included in the intention-to-treat
      analysis for response, and 485 in the primary analysis for response. The median
      age was 70 years. Although complete-remission rates were similar with R-FC and R
      CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent
      with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter
      with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more
      patients in the R-FC group died during the first remission (10% vs. 4%).
      Hematologic toxic effects occurred more frequently in the R-FC group than in the
      R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and
      14%, respectively). In 274 of the 316 patients who were randomly assigned to
      maintenance therapy, rituximab reduced the risk of progression or death by 45%
      (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for
      progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among
      patients who had a response to R-CHOP, maintenance therapy with rituximab
      significantly improved overall survival (4-year survival rate, 87%, vs. 63% with
      interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance
      therapy with rituximab is effective for older patients with mantle-cell lymphoma.
      (Funded by the European Commission and others; ClinicalTrials.gov number,
      NCT00209209.).

PMID- 22873531
TI  - Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.
AB  - BACKGROUND: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that
      is being investigated for the treatment of rheumatoid arthritis. METHODS: In this
      12-month, phase 3 trial, 717 patients who were receiving stable doses of
      methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of
      tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At
      month 3, patients in the placebo group who did not have a 20% reduction from
      baseline in the number of swollen and tender joints were switched in a blinded
      fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all
      patients still receiving placebo were switched to tofacitinib in a blinded
      fashion. The three primary outcome measures were a 20% improvement at month 6 in
      the American College of Rheumatology scale (ACR 20); the change from baseline to
      month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ
      DI) (which ranges from 0 to 3, with higher scores indicating greater disability);
      and the percentage of patients at month 6 who had a Disease Activity Score for 28
      joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less
      than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater
      disease activity). RESULTS: At month 6, ACR 20 response rates were higher among
      patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively)
      and among those receiving adalimumab (47.2%) than among those receiving placebo
      (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the
      HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR)
      below 2.6 at month 6 in the active-treatment groups than in the placebo group.
      Adverse events occurred more frequently with tofacitinib than with placebo, and
      pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group.
      Tofacitinib was associated with an increase in both low-density and high-density
      lipoprotein cholesterol levels and with reductions in neutrophil counts.
      CONCLUSIONS: In patients with rheumatoid arthritis receiving background
      methotrexate, tofacitinib was significantly superior to placebo and was
      numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard
      ClinicalTrials.gov number, NCT00853385.).

PMID- 22873534
TI  - Clinical practice. Diagnosis of diabetes.

PMID- 22873533
TI  - Prospective trial of a pediatric ventricular assist device.
AB  - BACKGROUND: Options for mechanical circulatory support as a bridge to heart
      transplantation in children with severe heart failure are limited. METHODS: We
      conducted a prospective, single-group trial of a ventricular assist device
      designed specifically for children as a bridge to heart transplantation. Patients
      16 years of age or younger were divided into two cohorts according to body
      surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients
      in each group. Survival in the two cohorts receiving mechanical support (with
      data censored at the time of transplantation or weaning from the device owing to
      recovery) was compared with survival in two propensity-score-matched historical
      control groups (one for each cohort) undergoing extracorporeal membrane
      oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival
      time had not been reached at 174 days, whereas in the matched ECMO group, the
      median survival was 13 days (P<0.001 by the log-rank test). For participants in
      cohort 2 and the matched ECMO group, the median survival was 144 days and 10
      days, respectively (P<0.001 by the log-rank test). Serious adverse events in
      cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients,
      respectively), infection (in 63% and 50%), and stroke (in 29% and 29%).
      CONCLUSIONS: Our trial showed that survival rates were significantly higher with
      the ventricular assist device than with ECMO. Serious adverse events, including
      infection, stroke, and bleeding, occurred in a majority of study participants.
      (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan
      Product Development; ClinicalTrials.gov number, NCT00583661.).

PMID- 22873535
TI  - Images in clinical medicine. Halitosis and sensory loss.

PMID- 22873536
TI  - Case records of the Massachusetts General Hospital. Case 24-2012. A 38-year-old
      man with abdominal pain and altered mental status.

PMID- 22873537
TI  - Kinase inhibition--a new approach to the treatment of rheumatoid arthritis.

PMID- 22873538
TI  - Pediatric ventricular assist devices--first steps for babies.

PMID- 22873540
TI  - Preclinical success against Alzheimer's disease with an old drug.

PMID- 22873542
TI  - Lenalidomide for multiple myeloma.

PMID- 22873544
TI  - Coffee drinking and mortality.

PMID- 22873545
TI  - Coffee drinking and mortality.

PMID- 22873546
TI  - Coffee drinking and mortality.

PMID- 22873548
TI  - Off-pump or on-pump coronary-artery bypass grafting.

PMID- 22873550
TI  - Whistling in the dark.

PMID- 22873552
TI  - More on chronic cyclic non-nephrogenic magnesium depletion without losses.

PMID- 22873553
TI  - Prevalence and monitoring of oligosecretory myeloma.

PMID- 22873557
TI  - Images in clinical medicine. Green teeth in neonatal sepsis.

PMID- 22873558
TI  - Ultrathin antifouling coatings with stable surface zwitterionic functionality by
      initiated chemical vapor deposition (iCVD).
AB  - Antifouling thin films of poly[N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)
      co-2-(dimethylamino)ethyl methacrylate-co-ethylene glycol dimethacrylate] (PDDE)
      were synthesized via a substrate-independent and all-dry-initiated chemical vapor
      deposition (iCVD) technique followed by a diffusion-limited vapor-phase reaction
      with 1,3-propane sultone. Coated surfaces exhibited very low absorption of
      various foulants including bovine serum albumin (BSA), humic acid (HA), and
      sodium alginate (SA), as measured with the quartz crystal microbalance with
      dissipation monitoring (QCM-D). The fouling by humic acid was dependent on the
      presence of divalent cations such as Ca(2+). Both depth profiling and angle
      resolved X-ray photoelectron spectroscopy (XPS) measurements indicated that the
      zwitterionic groups were highly concentrated in the top ~3 nm of the film. The
      contact angle measurements revealed a limited degree of surface chain
      reorganization upon contacting water. The dynamic contact angles remained
      unchanged after 100 days of storage in air, indicating the stability of the
      interface. The coating was substrate-independent, and the film was conformal on
      surface nanostructures including trenches, reverse osmosis membranes, and
      electrospun nanofiber mats.

PMID- 22873559
TI  - Corpus callosum area in amyotrophic lateral sclerosis.

PMID- 22873560
TI  - Processing and memory for emotional and neutral material in amyotrophic lateral
      sclerosis.
AB  - Several studies have reported changes in emotional memory and processing in
      people with ALS (pwALS). In this study, we sought to analyse differences in
      emotional processing and memory between pwALS and healthy controls and to
      investigate the relationship between emotional memory and self-reported
      depression. Nineteen pwALS and 19 healthy controls were assessed on measures of
      emotional processing, emotional memory, verbal memory and depression. Although
      pwALS and controls did not differ significantly on measures of emotional memory,
      a subgroup of patients performed poorly on an emotional recognition task. With
      regard to emotional processing, pwALS gave significantly stronger ratings of
      emotional valence to positive words than to negative words. Higher ratings of
      emotional words were associated with better recall in controls but not pwALS.
      Self-reported depression and emotional processing or memory variables were not
      associated in either group. In conclusion, the results from this small study
      suggest that a subgroup of pwALS may show weakened 'emotional enhancement',
      although in the current sample this may reflect general memory impairment rather
      than specific changes in emotional memory. Nonetheless, different patterns of
      processing of emotionally-salient material by pwALS may have care and management
      related implications.

PMID- 22873561
TI  - TDP-43 plasma levels are higher in amyotrophic lateral sclerosis.
AB  - Our objective was to investigate TDP-43 plasma levels in patients with
      amyotrophic lateral sclerosis (ALS). TDP-43 has been identified as a major
      component of protein inclusions in the brain of patients with ALS; mutations in
      the corresponding gene (TARDBP) have also been identified. Although increased TDP
      43 levels have been reported in the cerebrospinal fluid, plasma levels have not
      yet been assessed in patients with ALS. TDP-43 levels were quantified by sandwich
      ELISA in plasma of 219 patients and 100 controls. In addition, we sequenced exon
      6 of TARDBP, and performed longitudinal TDP-43 plasma measurements in a subset of
      patients. Results showed that TDP-43 plasma levels were significantly increased
      in patients with ALS (p=0.023) and we found a positive correlation with age in
      patients and controls. Longitudinal measurements of TDP-43 plasma levels showed
      an increase in only one patient, with stable levels in five others. Three TARDBP
      variations were identified in the ALS group (1.7%), but the association with TDP
      43 plasma levels was ambiguous. In conclusion, our data indicate that TDP-43
      plasma levels may have potential as a marker for ALS. A genotype-phenotype
      relationship could not, however, be established in this cohort.

PMID- 22873563
TI  - Amyotrophic lateral sclerosis: a hormonal condition?
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disorder in
      adults. This fatal condition, due to degeneration of upper and lower motor
      neurons in spinal and bulbar myotomes, leads to death from respiratory failure
      after median disease duration of 36 months. ALS is sporadic in more than 90% of
      cases and familial in the remaining cases.   Most studies show male predominance
      with a gender ratio of 3:2, but gender differences are age related. The phenotype
      of ALS is also different in males and females with a predominance of limb onset
      in males and bulbar onset in females. While age and site of onset impact survival
      rate, and are both related to gender, gender by itself has not clearly been shown
      to have an effect on survival. Given this complex relationship between gender and
      ALS, we developed a hypothesis about hormone involvement in ALS aetiology by
      suggesting protective effect of oestrogens and adverse effect of androgens.

PMID- 22873562
TI  - ALS untangled No. 17: "when ALS is lyme".

PMID- 22873564
TI  - Replication of association of CHRNA4 rare variants with sporadic amyotrophic
      lateral sclerosis: the Italian multicentre study.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels
      widely expressed throughout the mammalian brain, including bulbar and spinal
      motor neurons. They are involved in neuroprotection and in control of release of
      many neurotransmitters, including glutamate. Previous data raised the hypothesis
      that rare variants in the region coding the intracellular loop subunits of nAChRs
      might represent one of several genetic risk factors for SALS. The aim of present
      study was to replicate the study in an independent cohort of ALS patients. We
      analysed 718 sporadic ALS patients from five Italian ALS centres and 1300
      ethnically matched controls. We focused primarily on CHRNA4, encoding alpha4
      subunit, since most mutations were previously detected in this gene. We observed
      a significant association between CHRNA4 mutations and ALS (OR 2.91; 95% CI
      1.4080-6.0453; p = 0.0056). Most mutations detected in patients were not present
      in the dbSNP134 and in 3500 ethnically matched control chromosomes and affected
      evolutionary conserved amino acid residues. In conclusion, the present data
      confirm that CHRNA4 variants are overrepresented in SALS strengthening the
      hypothesis can they act as predisposing genetic factors for SALS.

PMID- 22873565
TI  - Economic cost of home-telemonitoring care for BiPAP-assisted ALS individuals.
AB  - Our objective was to measure direct (hospital and NHS) and indirect
      (patient/caregiver) costs of following up in-home compliance to non-invasive
      ventilation via wireless modem. We constructed a prospective controlled trial of
      40 consecutive ALS home-ventilated patients, randomly assigned according to their
      residence area to G1 (nearby hospital, office-based follow-up) and G2 (outside
      hospital area, telemetry device-based follow-up). Total NHS direct cost
      encompassed costs related to outpatients' visits (office and emergency room) and
      hospitalizations. Hospital direct costs included transportation to/from hospital,
      office visit per hour cost and equipment maintenance. Non-medical costs
      considered days of wages lost due to absenteeism. G1 included 20 patients aged 60
      +/- 10 years and G2 included 19 patients aged 62 +/- 13 years. Results showed
      that no differences were found regarding clinical/demographic characteristics at
      admission. NHS costs showed a 55% reduction in average total costs with a
      statistically significant decrease of 81% in annual costs per patient in G2.
      Hospital costs were found to be significantly higher in G2 with regard to total
      costs (64% average increase) but not annual costs (7%). No statistical difference
      was found with regard to expenses from absenteeism. In conclusion, at the cost of
      an initial financial constraint to the hospital per year (non-significant),
      telemonitoring is cost-effective, representing major cost savings to the NHS in
      the order of 700 euros/patient/year.

PMID- 22873567
TI  - Excited-state interactions in diastereomeric flurbiprofen-thymine dyads.
AB  - Excited-state interactions between (S)- or (R)-flurbiprofen ((S)- or (R)-FBP) and
      thymidine (dThd) covalently linked in dyads 1 or 2 have been investigated. In
      both dyads, the only emitting species is (1)FBP*, but with a lower fluorescence
      quantum yield (phi(F)) and a shorter fluorescence lifetime (tau(F)) than when
      free in solution. These results indicate that dynamic quenching occurs either by
      electron transfer or via exciplex formation, with FBP as the charge-donating
      species. In acetonitrile, both mechanisms are favored, while in dioxane exciplex
      formation is predominating. Isomer 1 displays lower values of phi(F) and tau(F)
      than its analogue 2, indicating that the relative spatial arrangement of the
      chromophores plays a significant role. The triplet quantum yields (phi(T)) of 1
      and 2 are significantly higher than the expectations based solely on (1)FBP*-dThd
      intersystem crossing quantum yields (phi(ISC)), with phi(T) (1) > phi(T) (2).
      This can be explained in terms of intramolecular charge recombination at the
      radical ion pairs and/or the exciplexes, which would be again dependent on
      geometrical factors. The triplet lifetimes (tau(T)) of (3)FBP*-dThd and free
      (3)FBP* are similar, indicating the lack of excited-state interactions at this
      stage. The FBP-dThd dyads could, in principle, constitute appropriate model
      systems for the elucidation of the excited-state interactions in noncovalent DNA
      ligand complexes.

PMID- 22873566
TI  - Marker-based linkage map of Andean common bean (Phaseolus vulgaris L.) and
      mapping of QTLs underlying popping ability traits.
AB  - BACKGROUND: Nuna bean is a type of ancient common bean (Phaseolus vulgaris L.)
      native to the Andean region of South America, whose seeds possess the unusual
      property of popping. The nutritional features of popped seeds make them a healthy
      low fat and high protein snack. However, flowering of nuna bean only takes place
      under short-day photoperiod conditions, which means a difficulty to extend
      production to areas where such conditions do not prevail. Therefore, breeding
      programs of adaptation traits will facilitate the diversification of the bean
      crops and the development of new varieties with enhanced healthy properties.
      Although the popping trait has been profusely studied in maize (popcorn), little
      is known about the biology and genetic basis of the popping ability in common
      bean. To obtain insights into the genetics of popping ability related traits of
      nuna bean, a comprehensive quantitative trait loci (QTL) analysis was performed
      to detect single-locus and epistatic QTLs responsible for the phenotypic variance
      observed in these traits. RESULTS: A mapping population of 185 recombinant inbred
      lines (RILs) derived from a cross between two Andean common bean genotypes was
      evaluated for three popping related traits, popping dimension index (PDI),
      expansion coefficient (EC), and percentage of unpopped seeds (PUS), in five
      different environmental conditions. The genetic map constructed included 193 loci
      across 12 linkage groups (LGs), covering a genetic distance of 822.1 cM, with an
      average of 4.3 cM per marker. Individual and multi-environment QTL analyses
      detected a total of nineteen single-locus QTLs, highlighting among them the co
      localized QTLs for the three popping ability traits placed on LGs 3, 5, 6, and 7,
      which together explained 24.9, 14.5, and 25.3% of the phenotypic variance for
      PDI, EC, and PUS, respectively. Interestingly, epistatic interactions among QTLs
      have been detected, which could have a key role in the genetic control of
      popping. CONCLUSIONS: The QTLs here reported constitute useful tools for marker
      assisted selection breeding programs aimed at improving nuna bean cultivars, as
      well as for extending our knowledge of the genetic determinants and genotype x
      environment interaction involved in the popping ability traits of this bean crop.

PMID- 22873569
TI  - Filter paper collection of Plasmodium falciparum mRNA for detecting low-density
      gametocytes.
AB  - BACKGROUND: Accurate sampling of sub-microscopic gametocytes is necessary for
      epidemiological studies to identify the infectious reservoir of Plasmodium
      falciparum. Detection of gametocyte mRNA achieves sensitive detection, but
      requires careful handling of samples. Filter papers can be used for collecting
      RNA samples, but rigorous testing of their capacity to withstand adverse storage
      conditions has not been fully explored. METHODS: Three gametocyte dilutions:
      10/MUL, 1.0/MUL and 0.1/MUL were spotted onto WhatmanTM 903 Protein Saver Cards,
      FTA Classic Cards and 3MM filter papers that were stored under frozen, cold chain
      or tropical conditions for up to 13 weeks . RNA was extracted, then detected by
      quantitative nucleic acid sequence-based amplification (QT-NASBA) and reverse
      transcriptase PCR (RT-PCR). RESULTS: Successful gametocyte detection was more
      frequently observed from the Whatman 903 Protein Saver Card compared to the
      Whatman FTA Classic Card, by both techniques (p<0.0001). When papers were stored
      at higher temperatures, a loss in sensitivity was experienced for the FTA Classic
      Card but not the 903 Protein Saver Card or Whatman 3MM filter paper. The
      sensitivity of gametocyte detection was decreased when papers were stored at high
      humidity. CONCLUSIONS: This study indicates the Whatman 903 Protein Saver Card is
      better for Pfs25 mRNA sampling compared to the Whatman FTA Classic Card, and that
      the Whatman 3MM filter paper may prove to be a satisfactory cheaper option for
      Pfs25 mRNA sampling. When appropriately dried, filter papers provide a useful
      approach to Pfs25 mRNA sampling, especially in settings where storage in RNA
      protecting buffer is not possible.

PMID- 22873568
TI  - Modeling RNA polymerase interaction in mitochondria of chordates.
AB  - BACKGROUND: In previous work, we introduced a concept, a mathematical model and
      its computer realization that describe the interaction between bacterial and
      phage type RNA polymerases, protein factors, DNA and RNA secondary structures
      during transcription, including transcription initiation and termination. The
      model accurately reproduces changes of gene transcription level observed in
      polymerase sigma-subunit knockout and heat shock experiments in plant plastids.
      The corresponding computer program and a user guide are available at
      http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of
      transcription and (partially) translation processes in the mitochondria of frog,
      rat and human. Notably, mitochondria possess only phage-type polymerases. We
      consider the entire mitochondrial genome so that our model allows RNA polymerases
      to complete more than one circle on the DNA strand. RESULTS: Our model of RNA
      polymerase interaction during transcription initiation and elongation accurately
      reproduces experimental data obtained for plastids. Moreover, it also reproduces
      evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of
      frog, human with or without the MELAS mutation, and rat with normal (euthyroid)
      or hyposecretion of thyroid hormone (hypothyroid). The transcription
      characteristics predicted by the model include: (i) the fraction of polymerases
      terminating at a protein-dependent terminator in both directions (the terminator
      polarization), (ii) the binding intensities of the regulatory protein factor
      (mTERF) with the termination site and, (iii) the transcription initiation
      intensities (initiation frequencies) of all promoters in all five conditions
      (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat
      with aberrant mtDNA methylation). Using the model, absolute levels of all gene
      transcription can be inferred from an arbitrary array of the three transcription
      characteristics, whereas, for selected genes only relative RNA concentrations
      have been experimentally determined. Conversely, these characteristics and
      absolute transcription levels can be obtained using relative RNA concentrations
      and RNA half-lives known from various experimental studies. In this case, the
      "inverse problem" is solved with multi-objective optimization. CONCLUSIONS: In
      this study, we demonstrate that our model accurately reproduces all relevant
      experimental data available for plant plastids, as well as the mitochondria of
      chordates. Using experimental data, the model is applied to estimate binding
      intensities of phage-type RNA polymerases to their promoters as well as
      predicting terminator characteristics, including polarization. In addition, one
      can predict characteristics of phage-type RNA polymerases and the transcription
      process that are difficult to measure directly, e.g., the association between the
      promoter's nucleotide composition and the intensity of polymerase binding. To
      illustrate the application of our model in functional predictions, we propose a
      possible mechanism for MELAS syndrome development in human involving a decrease
      of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we
      describe how changes in methylation patterns of the mTERF binding site and three
      promoters in hypothyroid rat correlate with changes in intensities of the mTERF
      binding and transcription initiations. Finally, we introduce an auxiliary model
      to describe the interaction between polysomal mRNA and ribonucleases.

PMID- 22873570
TI  - Preparation of silica nanospheres and porous polymer membranes with controlled
      morphologies via nanophase separation.
AB  - We successfully synthesized two different structures, silica nanospheres and
      porous polymer membranes, via nanophase separation, based on a sol-gel process.
      Silica sol, which was in situ polymerized from tetraorthosilicate, was used as a
      precursor. Subsequently, it was mixed with a polymer that was used as a matrix
      component. It was observed that nanophase separation occurred after the mixing of
      polymer with silica sol and subsequent evaporation of solvents, resulting in
      organizing various structures, from random network silica structures to silica
      spheres. In particular, silica nanospheres were produced by manipulating the
      mixing ratio of polymer to silica sol. The size of silica beads was gradually
      changed from micro- to nanoscale, depending on the polymer content. At the same
      time, porous polymer membranes were generated by removing the silica component
      with hydrofluoric acid. Furthermore, porous carbon membranes were produced using
      carbon source polymer through the carbonization process.

PMID- 22873571
TI  - Can personal qualities of medical students predict in-course examination success
      and professional behaviour? An exploratory prospective cohort study.
AB  - BACKGROUND: Over two-thirds of UK medical schools are augmenting their selection
      procedures for medical students by using the United Kingdom Clinical Aptitude
      Test (UKCAT), which employs tests of cognitive and non-cognitive personal
      qualities, but clear evidence of the tests' predictive validity is lacking. This
      study explores whether academic performance and professional behaviours that are
      important in a health professional context can be predicted by these measures,
      when taken before or very early in the medical course. METHODS: This prospective
      cohort study follows the progress of the entire student cohort who entered Hull
      York Medical School in September 2007, having taken the UKCAT cognitive tests in
      2006 and the non-cognitive tests a year later. This paper reports on the
      students' first and second academic years of study. The main outcome measures
      were regular, repeated tutor assessment of individual students' interpersonal
      skills and professional behaviour, and annual examination performance in the
      three domains of recall and application of knowledge, evaluation of data, and
      communication and practical clinical skills. The relationships between non
      cognitive test scores, cognitive test scores, tutor assessments and examination
      results were explored using the Pearson product-moment correlations for each
      group of data; the data for students obtaining the top and bottom 20% of the
      summative examination results were compared using Analysis of Variance. RESULTS:
      Personal qualities measured by non-cognitive tests showed a number of
      statistically significant relationships with ratings of behaviour made by tutors,
      with performance in each year's objective structured clinical examinations
      (OSCEs), and with themed written summative examination marks in each year.
      Cognitive ability scores were also significantly related to each year's
      examination results, but seldom to professional behaviours. The top 20% of
      examination achievers could be differentiated from the bottom 20% on both non
      cognitive and cognitive measures. CONCLUSIONS: This study shows numerous
      significant relationships between both cognitive and non-cognitive test scores,
      academic examination scores and indicators of professional behaviours in medical
      students. This suggests that measurement of non-cognitive personal qualities in
      applicants to medical school could make a useful contribution to selection and
      admission decisions. Further research is required in larger representative
      groups, and with more refined predictor measures and behavioural assessment
      methods, to establish beyond doubt the incremental validity of such measures over
      conventional cognitive assessments.

PMID- 22873572
TI  - The role of organic linkers in directing DNA self-assembly and significantly
      stabilizing DNA duplexes.
AB  - We show a simple method to control both the stability and the self-assembly
      behavior of DNA structures. By connecting two adjacent duplexes with small
      synthetic linkers, factors such as linker rigidity and DNA strand orientation can
      increase the thermal denaturation temperature of 17 base-pair duplexes by up to
      10  degrees C, and significantly increase the cooperativity of melting of the two
      duplexes. The same DNA sequence can thus be tuned to melt at vastly different
      temperatures by selecting the linker structure and DNA-to-linker connectivity. In
      addition, a small rigid m-triphenylene linker directly affects the self-assembly
      product distribution. With this linker, changes in the orientation of the linked
      strands (e.g., 5'3' vs 3'3') can lead to dramatic changes in the self-assembly
      behavior, from the formation of cyclic dimer and tetramer to higher-order
      oligomers. These variations can be readily predicted using a simple strand-end
      alignment model.

PMID- 22873573
TI  - Bioanalytical assessment of the formation of disinfection byproducts in a
      drinking water treatment plant.
AB  - Disinfection of drinking water is the most successful measure to reduce water
      borne diseases and protect health. However, disinfection byproducts (DBPs) formed
      from the reaction of disinfectants such as chlorine and monochloramine with
      organic matter may cause bladder cancer and other adverse health effects. In this
      study the formation of DBPs through a full-scale water treatment plant serving a
      metropolitan area in Australia was assessed using in vitro bioanalytical tools,
      as well as through quantification of halogen-specific adsorbable organic halogens
      (AOXs), characterization of organic matter, and analytical quantification of
      selected regulated and emerging DBPs. The water treatment train consisted of
      coagulation, sand filtration, chlorination, addition of lime and fluoride,
      storage, and chloramination. Nonspecific toxicity peaked midway through the
      treatment train after the chlorination and storage steps. The dissolved organic
      matter concentration decreased after the coagulation step and then essentially
      remained constant during the treatment train. Concentrations of AOXs increased
      upon initial chlorination and continued to increase through the plant, probably
      due to increased chlorine contact time. Most of the quantified DBPs followed a
      trend similar to that of AOXs, with maximum concentrations observed in the final
      treated water after chloramination. The mostly chlorinated and brominated DBPs
      formed during treatment also caused reactive toxicity to increase after
      chlorination. Both genotoxicity with and without metabolic activation and the
      induction of the oxidative stress response pathway showed the same pattern as the
      nonspecific toxicity, with a maximum activity midway through the treatment train.
      Although measured effects cannot be directly translated to adverse health
      outcomes, this study demonstrates the applicability of bioanalytical tools to
      investigate DBP formation in a drinking water treatment plant, despite bioassays
      and sample preparation not yet being optimized for volatile DBPs. As such, the
      bioassays are useful as monitoring tools as they provide sensitive responses even
      at low DBP levels.

PMID- 22873574
TI  - An evaluation of an intervention sequence outline in positive behaviour support
      for people with autism and severe escape-motivated challenging behaviour.
AB  - BACKGROUND: Positive behaviour support emphasises the impact of contextual
      variables to enhance participation, choice, and quality of life. This study
      evaluates a sequence for implementing changes to key contextual variables for 4
      individuals. Interventions were maintained and data collection continued over a 3
      year period. METHOD: Functional assessments were conducted with 4 individuals
      with exceptionally severe challenging behaviours. Interventions were based on the
      multi-element model of behavioural support (LaVigna & Willis, 2005a). Dependent
      variables were behavioural ratings of (1) frequency, (2) episodic severity, (3)
      episodic management difficulty, and measures of (4) mental health status, and (5)
      quality of life. The intervention sequence was low arousal environment, rapport
      building, predictability, functionally equivalent skills teaching, and
      differential reinforcement strategies. RESULTS: Substantial reductions in target
      behaviours were observed, along with incremental improvement in mental health
      scores and quality-of-life scores. CONCLUSION: The study demonstrates the
      efficacy of positive behaviour support for people with exceptionally severe
      behaviour in individually designed services.

PMID- 22873575
TI  - A component analysis of positive behaviour support plans.
AB  - BACKGROUND: Positive behaviour support (PBS) emphasises multi-component
      interventions by natural intervention agents to help people overcome challenging
      behaviours. This paper investigates which components are most effective and which
      factors might mediate effectiveness. METHOD: Sixty-one staff working with
      individuals with intellectual disability and challenging behaviours completed
      longitudinal competency-based training in PBS. Each staff participant conducted a
      functional assessment and developed and implemented a PBS plan for one
      prioritised individual. A total of 1,272 interventions were available for
      analysis. Measures of challenging behaviour were taken at baseline, after 6
      months, and at an average of 26 months follow-up. RESULTS: There was a
      significant reduction in the frequency, management difficulty, and episodic
      severity of challenging behaviour over the duration of the study. Escape was
      identified by staff as the most common function, accounting for 77% of
      challenging behaviours. The most commonly implemented components of intervention
      were setting event changes and quality-of-life-based interventions. CONCLUSION:
      Only treatment acceptability was found to be related to decreases in behavioural
      frequency. No single intervention component was found to have a greater
      association with reductions in challenging behaviour.

PMID- 22873578
TI  - Exploring uncharted territories: predicting activity cliffs in structure-activity
      landscapes.
AB  - The notion of activity cliffs is an intuitive approach to characterizing
      structural features that play a key role in modulating biological activity of a
      molecule. A variety of methods have been described to quantitatively characterize
      activity cliffs, such as SALI and SARI. However, these methods are primarily
      retrospective in nature; highlighting cliffs that are already present in the data
      set. The current study focuses on employing a pairwise characterization of a data
      set to train a model to predict whether a new molecule will exhibit an activity
      cliff with one or more members of the data set. The approach is based on
      predicting a value for pairs of objects rather than the individual objects
      themselves (and thus allows for robust models even for small structure-activity
      relationship data sets). We extracted structure-activity data for several ChEMBL
      assays and developed random forest models to predict SALI values, from pairwise
      combinations of molecular descriptors. The models exhibited reasonable RMSE's
      though, surprisingly, performance on the more significant cliffs tended to be
      better than on the lesser ones. While the models do not exhibit very high levels
      of accuracy, our results indicate that they are able to prioritize molecules in
      terms of their ability to activity cliffs, thus serving as a tool to
      prospectively identify activity cliffs.

PMID- 22873579
TI  - Folate-PEG-appended dendrimer conjugate with alpha-cyclodextrin as a novel cancer
      cell-selective siRNA delivery carrier.
AB  - We previously reported that of the various polyamidoamine (PAMAM) STARBURST
      dendrimer (generation 3, G3) (dendrimer) conjugates with cyclodextrins (CyDs),
      the dendrimer (G3) conjugate with alpha-CyD having an average degree of
      substitution of 2.4 (alpha-CDE (G3)) has the greatest potential for a novel
      carrier for siRNA in vitro and in vivo. To improve the siRNA transfer activity
      and the lack of target specificity of alpha-CDE (G3), we prepared folate
      polyethylene glycol (PEG)-appended alpha-CDEs (G3) (Fol-PalphaCs) with various
      degrees of substitution of folate (DSF) and evaluated their siRNA transfer
      activity to folate receptor (FR)-overexpressing cancer cells in vitro and in
      vivo. Of the three Fol-PalphaCs (G3, DSF 2, 4 and 7), Fol-PalphaC (G3, DSF 4) had
      the highest siRNA transfer activity in KB cells (FR-positive). Fol-PalphaC (G3,
      DSF 4) was endocytosed into KB cells through FR. No cytotoxicity of the siRNA
      complex with Fol-PalphaC (G3, DSF 4) was observed in KB cells (FR-positive) or
      A549 cells (FR-negative) up to the charge ratio of 100/1 (carrier/siRNA). In
      addition, the siRNA complex with Fol-PalphaC (G3, DSF 4) showed neither
      interferon response nor inflammatory response. Importantly, the siRNA complex
      with Fol-PalphaC (G3, DSF 4) tended to show the in vivo RNAi effects after
      intratumoral injection and intravenous injection in tumor cells-bearing mice. The
      FITC-labeled siRNA and TRITC-labeled Fol-PalphaC (G3, DSF 4) were actually
      accumulated in tumor tissues after intravenous injection in the mice. In
      conclusion, the present results suggest that Fol-PalphaC (G3, DSF 4) could
      potentially be used as a FR-overexpressing cancer cell-selective siRNA delivery
      carrier in vitro and in vivo.

PMID- 22873580
TI  - A case-control study of occupation/industry and renal cell carcinoma risk.
AB  - BACKGROUND: The role of occupation in the etiology of renal cell carcinoma (RCC)
      is unclear. Here, we investigated associations between employment in specific
      occupations and industries and RCC, and its most common histologic subtype, clear
      cell RCC (ccRCC). METHODS: Between 2002 and 2007, a population-based case-control
      study of Caucasians and African Americans (1,217 cases; 1,235 controls) was
      conducted within the Detroit and Chicago metropolitan areas to investigate risk
      factors for RCC. As part of this study, occupational histories were ascertained
      through in-person interviews. We computed odds ratios (ORs) and 95% confidence
      intervals (CIs) relating occupation and industry to RCC risk using adjusted
      unconditional logistic regression models. RESULTS: Employment in the agricultural
      crop production industry for five years or more was associated with RCC (OR = 3.3
      [95% CI = 1.0-11.5]) and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for
      trend with duration of employment = 0.0050). Similarly, RCC risk was elevated for
      employment of five years or longer in non-managerial agricultural and related
      occupations (ORRCC = 2.1 [95% CI = 1.0-4.5]; ORccRCC = 3.1 [95% CI = 1.4-6.8]).
      Employment in the dry-cleaning industry was also associated with elevated risk
      (ORRCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; ORccRCC = 3.0 [95% CI = 1.2
      7.4], P for trend = 0.031). Suggestive elevated associations were observed for
      police/public safety workers, health care workers and technicians, and employment
      in the electronics, auto repair, and cleaning/janitorial services industries;
      protective associations were suggested for many white-collar jobs including
      computer science and administrative occupations as well employment in the
      business, legislative, and education industries. CONCLUSIONS: Our findings
      provide support for an elevated risk of RCC in the agricultural and dry-cleaning
      industries and suggest that these associations may be stronger for the ccRCC
      subtype. Additional studies are needed to confirm these findings.

PMID- 22873581
TI  - Renal tumors and second primary pancreatic tumors: a relationship with clinical
      impact?
AB  - BACKGROUND: The occurrence of synchronous or metachronous renal cell carcinoma
      and pancreatic tumors has been described only in a few cases in the scientific
      literature. The study of double primary cancers is important because it might
      provide understanding of a shared genetic basis of different solid tumors and to
      detect patients at risk for secondary malignancy. METHODS: In a combined analysis
      of patient registries from University Departments of Urology and Visceral
      Surgery, 1178 patients with pancreatic tumors and 518 patients with renal cell
      carcinoma treated between 2001 and 2008 were evaluated, RESULTS: Overall 16
      patients with renal cancer and synchronous (n = 6) or metachronous (n = 10)
      primary pancreatic tumors were detected. The median survival of all patients was
      12.6 months, for the patients with synchronous resections 25.7 months and for the
      patients with metachronous resections 12.2 months, respectively. CONCLUSIONS: The
      association between these two etiologies of malignancy demands more detailed
      epidemiological and molecular investigation. Clinical outcomes would support a
      resection as a recommended clinically valid option.

PMID- 22873582
TI  - Enrichment in a stoichiometric model of two producers and one consumer.
AB  - We consider a stoichiometric population model of two producers and one consumer.
      Stoichiometry can be thought of as the tracking of food quality in addition to
      food quantity. Our model assumes a reduced rate of conversion of biomass from
      producer to consumer when food quality is low. The model is open for carbon but
      closed for nutrient. The introduction of the second producer, which competes with
      the first, leads to new equilibria, new limit cycles, and new bifurcations. The
      focus of this paper is on the bifurcations which are the result of enrichment.
      The primary parameters we vary are the growth rates of both producers. Secondary
      variable parameters are the total nutrients in the system, and the producer
      nutrient uptake rates. The possible equilibria are: no-life, one-producer,
      coexistence of both producers, the consumer coexisting with either producer, and
      the consumer coexisting with both producers. We observe limit cycles in the
      latter three coexistence combinations. Bifurcation diagrams along with
      corresponding representative time series summarize the behaviours observed for
      this model.

PMID- 22873583
TI  - On several conjectures from evolution of dispersal.
AB  - We address several conjectures raised in Cantrell et al. [Evolution of dispersal
      and ideal free distribution, Math. Biosci. Eng. 7 (2010), pp. 17-36 [ 9 ]]
      concerning the dynamics of a diffusion-advection-competition model for two
      competing species. A conditional dispersal strategy, which results in the ideal
      free distribution of a single population at equilibrium, was found in Cantrell et
      al. [ 9 ]. It was shown in [ 9 ] that this special dispersal strategy is a local
      evolutionarily stable strategy (ESS) when the random diffusion rates of the two
      species are equal, and here we show that it is a global ESS for arbitrary random
      diffusion rates. The conditions in [ 9 ] for the coexistence of two species are
      substantially improved. Finally, we show that this special dispersal strategy is
      not globally convergent stable for certain resource functions, in contrast with
      the result from [ 9 ], which roughly says that this dispersal strategy is
      globally convergent stable for any monotone resource function.

PMID- 22873584
TI  - A size-structured model of bacterial growth and reproduction.
AB  - We consider a size-structured bacterial population model in which the rate of
      cell growth is both size- and time-dependent and the average per capita
      reproduction rate is specified as a model parameter. It is shown that the model
      admits classical solutions. The population-level and distribution-level
      behaviours of these solutions are then determined in terms of the model
      parameters. The distribution-level behaviour is found to be different from that
      found in similar models of bacterial population dynamics. Rather than convergence
      to a stable size distribution, we find that size distributions repeat in cycles.
      This phenomenon is observed in similar models only under special assumptions on
      the functional form of the size-dependent growth rate factor. Our main results
      are illustrated with examples, and we also provide an introductory study of the
      bacterial growth in a chemostat within the framework of our model.

PMID- 22873585
TI  - A coupled plankton system with instantaneous and delayed predation.
AB  - We present two simple plankton population models: one has instantaneous
      predation, another has delayed predation. The models consist of two coupled
      differential equations representing the interaction between phytoplankton and
      herbivorous zooplankton with additional effect of zooplankton predation by a
      constant fish population. We study the dynamical behaviour and investigate the
      conditions to guarantee the coexistence of two species, and address the stability
      and bifurcation under different density of fish, with or without the maturation
      time delay. Analytical methods and numerical simulations are used to obtain
      information about the qualitative behaviour of the models.

PMID- 22873586
TI  - A net reproductive number for periodic matrix models.
AB  - We give a definition of a net reproductive number R (0) for periodic matrix
      models of the type used to describe the dynamics of a structured population with
      periodic parameters. The definition is based on the familiar method of studying a
      periodic map by means of its (period-length) composite. This composite has an
      additive decomposition that permits a generalization of the Cushing-Zhou
      definition of R (0) in the autonomous case. The value of R (0) determines whether
      the population goes extinct (R (0)<1) or persists (R (0)>1). We discuss the
      biological interpretation of this definition and derive formulas for R (0) for
      two cases: scalar periodic maps of arbitrary period and periodic Leslie models of
      period 2. We illustrate the use of the definition by means of several examples
      and by applications to case studies found in the literature. We also make some
      comparisons of this definition of R (0) with another definition given recently by
      Bacaer.

PMID- 22873587
TI  - Stochastic epidemic models revisited: analysis of some continuous performance
      measures.
AB  - We deal with stochastic epidemic models having a set of absorbing states. The aim
      of the paper is to study some continuous characteristics of the epidemic. In this
      sense, we first extend the classical study of the length of an outbreak by
      investigating the whole probability distribution of the extinction time via
      Laplace transforms. Moreover, we also study two almost new epidemic descriptors,
      namely, the time until a non-infected individual becomes infected and the time
      until the individual is removed from the infective group. The obtained results
      are illustrated by numerical examples including an application to a stochastic
      SIS model for head lice infections.

PMID- 22873588
TI  - Global behavior of solutions of a periodically forced Sigmoid Beverton-Holt
      model.
AB  - Our aim in this paper is to investigate the boundedness, the extreme stability,
      and the periodicity of positive solutions of the periodically forced Sigmoid
      Beverton-Holt model:   [Formula: see text]   where {a ( n )} is a positive
      periodic sequence with period p and delta>0. In the special case when delta=1,
      the above equation reduces to the well-known periodic Pielou logistic equation
      which is known to be equivalent to the periodically forced Beverton-Holt model.

PMID- 22873589
TI  - A multi-structured epidemic problem with direct and indirect transmission in
      heterogeneous environments.
AB  - In this work, we analyse a deterministic epidemic mathematical model motivated by
      the propagation of a hantavirus (Puumala hantavirus) within a bank vole
      population (Clethrionomys glareolus). The host population is split into juvenile
      and adult individuals. A heterogeneous spatial chronological age and infection
      age structure is considered, and also indirect transmission via the environment.
      Maturation rates for juvenile individuals are adult density-dependent. For the
      reaction-diffusion systems with age structures derived, we give global existence,
      uniqueness and global boundedness results. A model with transmission to humans is
      also studied here.

PMID- 22873590
TI  - Mathematical modelling and experiments for the proliferation and differentiation
      of Drosophila intestinal stem cells II.
AB  - The Drosophila posterior midgut epithelium mainly consists of intestinal stem
      cells (ISCs); semi-differentiated cells, i.e. enteroblasts (EBs); and two types
      of fully differentiated cells, i.e. enteroendocrine cells (EEs) and enterocytes
      (ECs), which are controlled by signalling pathways. In [M. Kuwamura, K. Maeda,
      and T. Adachi-Yamada, Mathematical modeling and experiments for the proliferation
      and differentiation of Drosophila intestinal stem cells I, J. Biol. Dyn. 4
      (2009), pp. 248-257], on the basis of the functions of the Wnt and Notch
      signalling pathways, we studied the regulatory mechanism for the proliferation
      and differentiation of ISCs under the assumption that the Wnt proteins are
      supplied from outside the cellular system of ISCs. In this paper, we
      experimentally show that the Wnt proteins are specifically expressed in ISCs,
      EBs, and EEs, and theoretically show that the cellular system of ISCs can be self
      maintained under the assumption that the Wnt proteins are produced in the
      cellular system of ISCs. These results provide a useful basis for determining
      whether an environmental niche is required for maintaining the cellular system of
      tissue stem cells.

PMID- 22873592
TI  - Multi-species interactions in West Nile virus infection.
AB  - In this paper, we analyse the interaction of different species of birds and
      mosquitoes on the dynamics of West Nile virus (WNV) infection. We study the
      different transmission efficiencies of the vectors and birds and the impact on
      the possible outbreaks. We show that the basic reproductive number is the
      weighted mean of the basic reproductive number of each species, weighted by the
      relative abundance of its population in the location. These results suggest a
      possible explanation of why there are no outbreaks of WNV in Mexico.

PMID- 22873593
TI  - An evolutionary model of influenza A with drift and shift.
AB  - Influenza A virus evolves through two types of evolutionary mechanisms - drift
      and shift. These two evolutionary mechanisms allow the pathogen to infect us
      repeatedly, as well as occasionally create pandemics with large morbidity and
      mortality. Here we introduce a novel model that incorporates both evolutionary
      mechanisms. This necessitates the modelling of three types of strains - seasonal
      human strains, bird-to-human transmittable H5N1 strains and evolved pandemic H5N1
      strain. We define reproduction and invasion reproduction numbers and use them to
      establish the presence of dominant and coexistence equilibria. We find that the
      amino acid substitution structure of human influenza can destabilize the human
      influenza equilibrium and sustained oscillations are possible. We find that for
      low levels of infection in domestic birds, these oscillations persist, inducing
      oscillations in the number of humans infected with the avian flu strain. The
      oscillations have a period of 365 days, similar to the one that can be observed
      in the cumulative number of human H5N1 cases reported by the World Health
      Organization (WHO). Furthermore, we establish some partial global results on the
      competition of the strains.

PMID- 22873594
TI  - Synchronous versus asynchronous oscillations for antigenically varying Plasmodium
      falciparum with host immune response.
AB  - We consider a deterministic intra-host model for Plasmodium falciparum (Pf)
      malaria infection, which accounts for antigenic variation between n clonal
      variants of PfEMP1 and the corresponding host immune response (IR). Specifically,
      the model separates the IR into two components, specific and cross-reactive,
      respectively, in order to demonstrate that the latter can be a mechanism for the
      sequential appearance of variants observed in actual Pf infections. We show that
      a strong variant-specific IR relative to the cross-reactive IR favours the
      asynchronous oscillations (sequential dominance) over the synchronous
      oscillations in a number of ways. The decay rate of asynchronous oscillations is
      smaller than that for the synchronous oscillations, allowing for the parasite to
      survive longer. With the introduction of a delay in the stimulation of the IR, we
      show that only a small delay is necessary to cause persistent asynchronous
      oscillations and that a strong variant-specific IR increases the amplitude of the
      asynchronous oscillations.

PMID- 22873595
TI  - Global dynamics of a discrete two-species Lottery-Ricker competition model.
AB  - In this article, we study the global dynamics of a discrete two-dimensional
      competition model. We give sufficient conditions on the persistence of one
      species and the existence of local asymptotically stable interior period-2 orbit
      for this system. Moreover, we show that for a certain parameter range, there
      exists a compact interior attractor that attracts all interior points except
      Lebesgue measure zero set. This result gives a weaker form of coexistence which
      is referred to as relative permanence. This new concept of coexistence combined
      with numerical simulations strongly suggests that the basin of attraction of the
      locally asymptotically stable interior period-2 orbit is an infinite union of
      connected components. This idea may apply to many other ecological models.
      Finally, we discuss the generic dynamical structure that gives relative
      permanence.

PMID- 22873596
TI  - A logistic delay differential equation model for Chagas disease with interrupted
      spraying schedules.
AB  - This work studies a mathematical model for the dynamics of Chagas disease, a
      parasitic disease that affects humans and domestic mammals throughout rural areas
      in Central and South America. It presents a modified version of the model found
      in Spagnuolo et al. [A model for Chagas disease with controlled spraying, J.
      Biol. Dyn. 5 (2011), pp. 299-317] with a delayed logistic growth term, which
      captures an overshoot, beyond the vector carrying capacity, in the total vector
      population when the blood meal supply is large. It studies the steady states of
      the system in the case of constant coefficients without spraying, and the
      analysis shows that for given-averaged parameters, the endemic equilibrium is
      stable and attracting. The numerical simulations of the model dynamics with time
      dependent coefficients are shown when interruptions in the annual insecticide
      spraying cycles are taken into account. Simulations show that when there are
      spraying schedule interruptions, spraying may become ineffective when the blood
      meal supply is large.

PMID- 22873597
TI  - Evolutionary stability of ideal free nonlocal dispersal.
AB  - We study the evolutionary stability of nonlocal dispersal strategies that can
      produce ideal free population distributions, that is, distributions where all
      individuals have equal fitness and there is no net movement of individuals at
      equilibrium. We find that the property of producing ideal free distributions is
      necessary and often sufficient for evolutionary stability. Our results extend
      those already developed for discrete diffusion models on finite patch networks to
      the case of nonlocal dispersal models based on integrodifferential equations. The
      analysis is based on the use of comparison methods and the construction of sub-
      and supersolutions.

PMID- 22873598
TI  - Analytical and numerical approaches to coexistence of strains in a two-strain SIS
      model with diffusion.
AB  - This article introduces a two-strain spatially explicit SIS epidemic model with
      space-dependent transmission parameters. We define reproduction numbers of the
      two strains, and show that the disease-free equilibrium will be globally stable
      if both reproduction numbers are below one. We also introduce the invasion
      numbers of the two strains which determine the ability of each strain to invade
      the single-strain equilibrium of the other strain. The main question that we
      address is whether the presence of spatial structure would allow the two strains
      to coexist, as the corresponding spatially homogeneous model leads to competitive
      exclusion. We show analytically that if both invasion numbers are larger than
      one, then there is a coexistence equilibrium. We devise a finite element
      numerical method to numerically confirm the stability of the coexistence
      equilibrium and investigate various competition scenarios between the strains.
      Finally, we show that the numerical scheme preserves the positive cone and
      converges of first order in the time variable and second order in the space
      variables.

PMID- 22873599
TI  - Complex behaviour in four species food-web model.
AB  - A four-dimensional food-web system consisting of a bottom prey, two middle
      predators and a generalist predator has been developed with modified functional
      response. The system is well posed and dissipative. Some results on uniform
      persistence have been developed. The dynamics of the system is found to be
      chaotic for certain choice of parameters. The coexistence of all four species is
      possible in the form of periodic orbits/strange attractors for suitably chosen
      set of parameters.

PMID- 22873600
TI  - Global analysis of an SAIS model.
AB  - This paper is concerned with global analysis of an SAIS epidemiological model in
      a population of varying size introduced by Busenberg and van den Driessche. In
      this model the population is divided into three subgroups of susceptible,
      asymptomatic and infective individuals. It has been shown that this system has no
      periodic solutions and all its trajectories tend to the equilibria of the system.
      We use the Poincare Index theorem to determine the number of the equilibria and
      their stability properties. We have shown that bistability occurs for suitable
      values of parameters and found a set of examples of all possible dynamics of the
      system.

PMID- 22873601
TI  - Optimal strategy for controlling the spread of HIV/AIDS disease: a case study of
      South Africa.
AB  - HIV/AIDS disease continues to spread alarmingly despite the huge amounts of
      resources invested in fighting it. There is a need to integrate the series of
      control measures available to ensure a consistent reduction in the incidence of
      the disease pending the discovery of its cure. We present a deterministic model
      for controlling the spread of the disease using change in sexual habits and
      antiretroviral (ARV) therapy as control measures. We formulate a fixed time
      optimal control problem subject to the model dynamics with the goal of finding
      the optimal combination of the two control measures that will minimize the cost
      of the control efforts as well as the incidence of the disease. We estimate the
      model state initial conditions and parameter values from the demographic and
      HIV/AIDS data of South Africa. We use Pontryagin's maximum principle to derive
      the optimality system and solve the system numerically. Compared with the
      practice in most resource-limited settings where ARV treatment is given only to
      patients with full-blown AIDS, our simulation results suggest that starting the
      treatment as soon as the patients progress to the pre-AIDS stage of the disease
      coupled with appreciable change in the susceptible individuals' sexual habits
      reduces both the incidence and prevalence of the disease faster. In fact, the
      results predict that the implementation of the proposed strategy would drive new
      cases of the disease towards eradication in 10 years.

PMID- 22873602
TI  - Fatal disease and demographic Allee effect: population persistence and
      extinction.
AB  - If a healthy stable host population at the disease-free equilibrium is subject to
      the Allee effect, can a small number of infected individuals with a fatal disease
      cause the host population to go extinct? That is, does the Allee effect matter at
      high densities? To answer this question, we use a susceptible-infected epidemic
      model to obtain model parameters that lead to host population persistence (with
      or without infected individuals) and to host extinction. We prove that the
      presence of an Allee effect in host demographics matters even at large population
      densities. We show that a small perturbation to the disease-free equilibrium can
      eventually lead to host population extinction. In addition, we prove that
      additional deaths due to a fatal infectious disease effectively increase the
      Allee threshold of the host population demographics.

PMID- 22873603
TI  - Extracting the time-dependent transmission rate from infection data via solution
      of an inverse ODE problem.
AB  - The transmission rate of many acute infectious diseases varies significantly in
      time, but the underlying mechanisms are usually uncertain. They may include
      seasonal changes in the environment, contact rate, immune system response, etc.
      The transmission rate has been thought difficult to measure directly. We present
      a new algorithm to compute the time-dependent transmission rate directly from
      prevalence data, which makes no assumptions about the number of susceptible or
      vital rates. The algorithm follows our complete and explicit solution of a
      mathematical inverse problem for SIR-type transmission models. We prove that
      almost any infection profile can be perfectly fitted by an SIR model with
      variable transmission rate. This clearly shows a serious danger of overfitting
      such transmission models. We illustrate the algorithm with historic UK measles
      data and our observations support the common belief that measles transmission was
      predominantly driven by school contacts.

PMID- 22873604
TI  - Propagation of Turing patterns in a plankton model.
AB  - The paper is devoted to a reaction-diffusion system of equations describing
      phytoplankton and zooplankton distributions. Linear stability analysis of the
      model is carried out. Turing and Hopf stability boundaries are found. Emergence
      of two-dimensional spatial structures is illustrated by numerical simulations.
      Travelling waves between various stationary solutions are investigated.
      Transitions between homogeneous in space stationary solutions and Turing
      structures are studied.

PMID- 22873605
TI  - Modelling and optimal control of immune response of renal transplant recipients.
AB  - We consider the increasingly important and highly complex immunological control
      problem: control of the dynamics of immunosuppression for organ transplant
      recipients. The goal in this problem is to maintain the delicate balance between
      over-suppression (where opportunistic latent viruses threaten the patient) and
      under-suppression (where rejection of the transplanted organ is probable). First,
      a mathematical model is formulated to describe the immune response to both viral
      infection and introduction of a donor kidney in a renal transplant recipient.
      Some numerical results are given to qualitatively validate and demonstrate that
      this initial model exhibits appropriate characteristics of primary infection and
      reactivation for immunosuppressed transplant recipients. In addition, we develop
      a computational framework for designing adaptive optimal treatment regimes with
      partial observations and low-frequency sampling, where the state estimates are
      obtained by solving a second deterministic optimal tracking problem. Numerical
      results are given to illustrate the feasibility of this method in obtaining
      optimal treatment regimes with a balance between under-suppression and over
      suppression of the immune system.

PMID- 22873606
TI  - A generalized cholera model and epidemic-endemic analysis.
AB  - The transmission of cholera involves both human-to-human and environment-to-human
      pathways that complicate its dynamics. In this paper, we present a new and
      unified deterministic model that incorporates a general incidence rate and a
      general formulation of the pathogen concentration to analyse the dynamics of
      cholera. Particularly, this work unifies many existing cholera models proposed by
      different authors. We conduct equilibrium analysis to carefully study the complex
      epidemic and endemic behaviour of the disease. Our results show that despite the
      incorporation of the environmental component, there exists a forward
      transcritical bifurcation at R (0)=1 for the combined human-environment
      epidemiological model under biologically reasonable conditions.

PMID- 22873607
TI  - Extinction thresholds in deterministic and stochastic epidemic models.
AB  - The basic reproduction number, R(0), one of the most well-known thresholds in
      deterministic epidemic theory, predicts a disease outbreak if R(0)>1. In
      stochastic epidemic theory, there are also thresholds that predict a major
      outbreak. In the case of a single infectious group, if R(0)>1 and i infectious
      individuals are introduced into a susceptible population, then the probability of
      a major outbreak is approximately 1-(1/R(0))( i ). With multiple infectious
      groups from which the disease could emerge, this result no longer holds.
      Stochastic thresholds for multiple groups depend on the number of individuals
      within each group, i ( j ), j=1, ..., n, and on the probability of disease
      extinction for each group, q ( j ). It follows from multitype branching processes
      that the probability of a major outbreak is approximately [Formula: see text]. In
      this investigation, we summarize some of the deterministic and stochastic
      threshold theory, illustrate how to calculate the stochastic thresholds, and
      derive some new relationships between the deterministic and stochastic
      thresholds.

PMID- 22873608
TI  - Stability and stabilization for models of chemostats with multiple limiting
      substrates.
AB  - We study chemostat models in which multiple species compete for two or more
      limiting nutrients. First, we consider the case where the nutrient flow and
      species removal rates and input nutrient concentrations are all given as positive
      constants. In that case, we use Brouwer degree theory to give conditions
      guaranteeing that the models admit globally asymptotically stable componentwise
      positive equilibrium points, from all componentwise positive initial states. Then
      we use the results to develop stabilization theory for a class of controlled
      chemostats with two or more limiting nutrients. For cases where the dilution rate
      and input nutrient concentrations can be selected as controls, we prove that many
      different componentwise positive equilibria can be made globally asymptotically
      stable. This extends the existing control results for chemostats with one
      limiting nutrient. We demonstrate our methods in simulations.

PMID- 22873609
TI  - Allelopathy of plasmid-bearing and plasmid-free organisms competing for two
      complementary resources in a chemostat.
AB  - We consider a model of competition between plasmid-bearing and plasmid-free
      organisms for two complementary nutrients in a chemostat. We assume that the
      plasmid-bearing organism produces an allelopathic agent at the cost of its
      reproductive abilities which is lethal to plasmid-free organism. Our analysis
      leads to different thresholds in terms of the model parameters acting as
      conditions under which the organisms associated with the system cannot thrive
      even in the absence of competition. Local stability of the system is obtained in
      the absence of one or both the organisms. Also, global stability of the system is
      obtained in the presence of both the organisms. Computer simulations have been
      carried out to illustrate various analytical results.

PMID- 22873610
TI  - Vancomycin-resistant enterococci colonization-infection model: parameter impacts
      and outbreak risks.
AB  - Vancomycin-resistant enterococci (VRE) infections have been linked to increased
      mortality and costs. A new model of a VRE-infested intensive care unit (ICU) is
      introduced. It incorporates critical features including the difference between
      colonization and infection, the role of special preventive care treatment cycles,
      fitness cost, and antibiotic use. Five patient stages are considered:
      susceptible, colonized with and without special preventive care, and infected
      with and without treatment. Parameter ranges are determined representing
      different ICUs and incorporated to numerically simulate the model. Basic
      reproductive number of the infection is derived and the impacts of the parameters
      are analysed. Strategies to minimize VRE infections and outbreak risk are
      explored with a focus on efficient and simultaneous control of critical
      parameters. In particular, threshold values of the level of special preventive
      care and ICU compliance rate are given to achieve desired goals under various
      constraints.

PMID- 22873611
TI  - Estimates of tuberculosis progression rate of children in China.
AB  - In this paper, a discrete mathematical model is formulated to describe
      tuberculosis (TB) progression from latent infection to active disease. The data
      of national TB epidemiology surveys in China are taken to estimate the TB
      progression rate for children aged 0-14 years. The progression rate obtained in
      this paper gives a detailed and better estimate of TB progression rate among
      children.

PMID- 22873612
TI  - The dynamics of two-species allelopathic competition with optimal harvesting.
AB  - This paper analyses a bionomic model of two competitive species in the presence
      of toxicity with different harvesting efforts. An interesting dynamics in the
      first quadrant is analysed and two saddle-node bifurcations are detected for
      different bifurcation parameters. It is noted that under certain parametric
      restrictions, the model has a unique positive equilibrium point that is globally
      asymptotically stable whenever it is locally stable. It is also noted that the
      model can have zero, one or two feasible equilibria appearing through saddle-node
      bifurcations. The non-existence of a limit cycle in the interior of the first
      quadrant is also discussed using the Poincare-Dulac criteria. The saddle-node
      bifurcations are studied using Sotomayor's theorem. Numerical simulations are
      carried out to validate the analytical findings. The conditions for the existence
      of bionomic equilibria are discussed and an optimal harvesting policy is derived
      using Pontryagin's maximum principle.

PMID- 22873613
TI  - The dispersion of age differences between partners and the asymptotic dynamics of
      the HIV epidemic.
AB  - In this paper, the effect of a change in the distribution of age differences
      between sexual partners on the dynamics of the HIV epidemic is studied. In a
      gender- and age-structured compartmental model, it is shown that if the variance
      of the distribution is small enough, an increase in this variance strongly
      increases the basic reproduction number. Moreover, if the variance is large
      enough, the mean age difference barely affects the basic reproduction number. We,
      therefore, conclude that the local stability of the disease-free equilibrium
      relies more on the variance than on the mean.

PMID- 22873614
TI  - Discrete-time host-parasitoid models with pest control.
AB  - We propose a simple discrete-time host-parasitoid model to investigate the impact
      of external input of parasitoids upon the host-parasitoid interactions. It is
      proved that the input of the external parasitoids can eventually eliminate the
      host population if it is above a threshold and it also decreases the host
      population level in the unique interior equilibrium. It can simplify the host
      parasitoid dynamics when the host population practices contest competition. We
      then consider a corresponding optimal control problem over a finite time period.
      We also derive an optimal control model using a chemical as a control for the
      hosts. Applying the forward-backward sweep method, we solve the optimal control
      problems numerically and compare the optimal host populations with the host
      populations when no control is applied. Our study concludes that applying a
      chemical to eliminate the hosts directly may be a more effective control strategy
      than using the parasitoids to indirectly suppress the hosts.

PMID- 22873615
TI  - Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a
      Pavlov reflex of the immune response?
AB  - Chronic fatigue syndrome is a protracted illness condition (lasting even years)
      appearing with strong flu symptoms and systemic defiances by the immune system.
      Here, by means of statistical mechanics techniques, we study the most widely
      accepted picture for its genesis, namely a persistent acute mononucleosis
      infection, and we show how such infection may drive the immune system towards an
      out-of-equilibrium metastable state displaying chronic activation of both humoral
      and cellular responses (a state of full inflammation without a direct 'causes
      effect' reason). By exploiting a bridge with a neural scenario, we mirror killer
      lymphocytes T(K) and B cells to neurons and helper lymphocytes [Formula: see
      text] and [Formula: see text] to synapses, hence showing that the immune system
      may experience the Pavlov conditional reflex phenomenon: if the exposition to a
      stimulus (Epstein-Barr virus antigens) lasts for too long, strong internal
      correlations among B,T(K) and T(H) may develop ultimately resulting in a
      persistent activation even though the stimulus itself is removed. These outcomes
      are corroborated by several experimental findings.

PMID- 22873616
TI  - A mathematical epidemiological model of gram-negative Bartonella bacteria: does
      differential ectoparasite load fully explain the differences in infection
      prevalence of Rattus rattus and Rattus norvegicus?
AB  - We postulate that the large difference in infection prevalence, 24% versus 5%, in
      R. norvegicus and R. rattus, respectively, between these two co-occurring host
      species may be due to differences in ectoparasite and potential vector
      infestation rates. A compartmental model, representative of an infectious system
      containing these two Rattus species and two ectoparasite vectors, was constructed
      and the coefficients of the forces of infection determined mathematically. The
      maximum difference obtained by the model in the prevalence of Bartonella in the
      two Rattus species amounts to 4.6%, compared to the observed mean difference of
      19%. Results suggest the observed higher Bartonella infection prevalence in
      Rattus norvegicus compared to Rattus rattus, cannot be explained solely by higher
      ectoparasite load. The model also highlights the need for more detailed
      biological research on Bartonella infections in Rattus and the importance of the
      flea vector in the spread of this disease.

PMID- 22873617
TI  - Predicting attenuant and resonant 2-cycles in periodically forced discrete-time
      two-species population models.
AB  - Periodic environments may either enhance or suppress a population via resonant or
      attenuant cycles. We derive signature functions for predicting the responses of
      two competing populations to 2-periodic oscillations in six model parameters. Two
      of these parameters provide a non-trivial equilibrium and two provide the
      carrying capacities of each species in the absence of the other, but the
      remaining two are arbitrary and could be intrinsic growth rates. Each signature
      function is the sign of a weighted sum of the relative strengths of the
      oscillations of the perturbed parameters. Periodic environments are favourable
      for populations when the signature function is positive and are deleterious if
      the signature function is negative. We compute the signature functions of four
      classical, discrete-time two-species populations and determine regions in
      parameter space which are either favourable or detrimental to the populations.
      The six-parameter models include the Logistic, Ricker, Beverton-Holt, and Hassell
      models.

PMID- 22873618
TI  - Mathematical study on kinetics of hematopoietic stem cells--theoretical
      conditions for successful transplantation.
AB  - Numerous haematological diseases occur due to dysfunctions during homeostasis
      processes of blood cell production. Haematopoietic stem cell transplantation
      (HSCT) is a therapeutic option for the treatment of haematological malignancy and
      congenital immunodeficiency. Today, HSCT is widely applied as an alternative
      method to bone marrow transplantation; however, HSCT can be a risky procedure
      because of potential side effects and complications after transplantations.
      Although an optimal regimen to achieve successful HSCT while maintaining quality
      of life is to be developed, even theoretical considerations such as the
      evaluations of successful engraftments and proposals of clinical management
      strategies have not been fully discussed yet.   In this paper, we construct and
      investigate mathematical models that describe the kinetics of hematopoietic stem
      cell self-renewal and granulopoiesis under the influence of growth factors.
      Moreover, we derive theoretical conditions for successful HSCT, primarily on the
      basis of the idea that the basic reproduction number R (0) represents a threshold
      condition for a population to successfully grow in a given steady-state
      environment. Successful engraftment of transplanted haematopoietic stem cells
      (HSCs) is subsequently ensured by employing a concept of dynamical systems theory
      known as 'persistence'. On the basis of the implications from the modelling
      study, we discuss how the conditions derived for a successful HSCT are used to
      link to experimental studies.

PMID- 22873619
TI  - Permanence induced by life-cycle resonances: the periodical cicada problem.
AB  - Periodical cicadas are known for their unusually long life cycle for insects and
      their prime periodicity of either 13 or 17 years. One of the explanations for the
      prime periodicity is that the prime periods are selected to prevent cicadas from
      resonating with predators with submultiple periods. This paper considers this
      hypothesis by investigating a population model for periodical predator and prey.
      The study shows that if the periods of the two periodical species are not
      coprime, then the predator cannot resist the invasion of the prey. On the other
      hand, if the periods are coprime, then the predator can resist the invasion of
      the prey. It is also shown that if the periods are not coprime, then the life
      cycle resonance can induce a permanent system, in which no cohorts are missing in
      both populations. On the other hand, if the periods are coprime, then the system
      cannot be permanent.

PMID- 22873620
TI  - alpha-Acetal, omega-alkyne poly(ethylene oxide) as a versatile building block for
      the synthesis of glycoconjugated graft-copolymers suited for targeted drug
      delivery.
AB  - alpha-Acetal, omega-alkyne poly(ethylene oxide) was synthesized as building block
      of glycoconjugated poly(epsilon-caprolactone)-graft-poly(ethylene oxide) (PCL-g
      PEO) copolymers. The alkyne group is indeed instrumental for the PEGylation of a
      poly(alpha-azido-epsilon-caprolactone-co-epsilon-caprolactone) copolymer by the
      Huisgen's 1,3 dipolar cycloaddition, i.e., a click reaction. Moreover,
      deprotection of the acetal end-group of the hydrophilic PEO grafts followed by
      reductive amination of the accordingly formed aldehyde with an aminated sugar is
      a valuable strategy of glycoconjugation of the graft copolymer, whose micelles
      are then potential. A model molecule (fluoresceinamine) was first considered in
      order to optimize the experimental conditions for the reductive amination. These
      conditions were then extended to the decoration of the graft copolymer micelles
      with mannose, which is a targeting agent of dendritic cells and macrophages. The
      bioavailability of the sugar units at the surface of micelles was investigated by
      surface plasmon resonance (SPR). The same question was addressed to nanoparticles
      stabilized by the graft copolymer. Enzyme linked lectin assay (ELLA) confirmed
      the availability of mannose at the nanoparticle surface.

PMID- 22873621
TI  - Intra- and inter-rater reliability for judgement of cough following citric acid
      inhalation.
AB  - This study investigated the inter-rater and intra-rater reliability of subjective
      judgements of cough in patients following inhalation of citric acid. Eleven
      speech-language pathologists (SLPs) currently using cough reflex testing in their
      clinical practice (experienced raters) and 34 SLPs with no experience using cough
      reflex testing (inexperienced raters) were recruited to the study. Participants
      provided a rating of strong, weak, or absent to 10 video segments of cough
      responses elicited by inhalation of nebulized citric acid. The same video
      segments presented in a different sequence were re-evaluated by the same
      clinicians following a 15-minute break. Inter-rater reliability for experienced
      raters was calculated with a Fleiss' generalized kappa of .487; intra-rater
      reliability was higher with a kappa of .700. Inexperienced raters showed similar
      reliability, with kappa values for inter-rater and intra-rater reliability of
      .363 and .618, respectively. In conclusion, SLPs demonstrate only fair-to
      moderate reliability in subjectively judging a patient's cough response to citric
      acid. Experience in making cough judgements does not improve inter-rater
      reliability significantly. Further validity and reliability research, including
      an evaluation of the effect of training on judgement reliability, would be
      beneficial for guiding clinical policies.

PMID- 22873622
TI  - Sorafenib use in hepatocellular carcinoma in Japan: early experience and impact
      on clinical practice.

PMID- 22873623
TI  - Current status of hepatocellular carcinoma treatment in Japan: transarterial
      chemoembolization.
AB  - Transarterial chemoembolization (TACE) is the gold standard of treatment for
      intermediate-stage hepatocellular carcinoma (HCC), and involves the
      administration of cytotoxic drugs, with or without lipiodol, by means of a
      catheter directly to the hepatic artery followed by the administration of
      embolizing agents such as spherical gelatin or polyvinyl alcohol particles. There
      are currently no global guidelines regarding the dose, choice or combination of
      cytotoxic agents for TACE; therefore it is difficult to compare data from
      different TACE studies. Superselective TACE with lipiodol is the primary TACE
      procedure that offers satisfactory levels of local control with a lower risk of
      complications. Approximately 40-70% of patients with HCC with tumours sized 4-5
      cm or less attained complete tumour necrosis or remained local recurrence free
      for 3 years or longer following TACE. The early identification of
      unresponsiveness to TACE is important to allow for a timely switch to alternative
      therapies. The use of novel embolizing materials in TACE such as drug-eluting
      beads and radioembolization is likely to have beneficial effects. Indeed, the
      increase in angiogenic activity following TACE emphasizes the potential of TACE
      in combination with targeted molecular therapies such as the anti-angiogenesis
      inhibitor, sorafenib.

PMID- 22873624
TI  - Current status of hepatocellular carcinoma treatment in Japan: hepatic arterial
      infusion chemotherapy.
AB  - Hepatic arterial infusion chemotherapy (HAIC) allows the long-term administration
      of cytotoxic drugs to the liver. In Japan, HAIC has traditionally been used to
      treat patients with advanced hepatocellular carcinoma (HCC) with vascular
      invasion or multiple intrahepatic lesions, or both. The most common chemotherapy
      drugs used for HAIC in Japan are 5-fluorouracil and cisplatin. Although HAIC is
      associated with a high rate of response in some studies, it is not associated
      with a survival benefit. Furthermore, HAIC is associated with complications that
      are not observed with systemic chemotherapy, including peptic ulcer, arterial
      occlusion and port infection. A molecular targeted agent, sorafenib, recently
      became the standard therapy for advanced HCC on the basis of data from two
      randomized controlled trials. For this reason, the position of HAIC in the
      treatment of advanced HCC in Japan is under discussion. Clinical trials must be
      undertaken to establish standardized protocols and regimens for HAIC, and to
      determine the efficacy of HAIC in comparison with other therapies for HCC.
      Without evidence from such trials, HAIC may not find an established role in the
      treatment of HCC, and may even fall out of use. Recent evidence suggests that
      HAIC may be useful in combination with molecular targeted therapy; this is
      currently being investigated in a number of clinical trials.

PMID- 22873625
TI  - Current status of hepatocellular carcinoma treatment in Japan: practical use of
      sorafenib (Nexavar(r)).
AB  - The efficacy of sorafenib in hepatocellular carcinoma (HCC) has been demonstrated
      in two pivotal clinical trials: the European SHARP trial and a second trial that
      recruited patients in the Asia-Pacific region. Sorafenib was approved for the
      treatment of advanced HCC in Japan based on the results of these studies. This
      article presents experiences with sorafenib in patients with HCC at three
      institutions in Japan, representing the viewpoints of a liver surgeon and a
      hepatologist at university hospitals, and a hepatologist at a community hospital.
      The three physicians discuss representative cases and current clinical practice
      at their institutions, and their recommendations for the use of sorafenib in the
      wider clinical setting. Overall, the experiences at these institutions show that
      sorafenib is most effective when administered for a long time, and the management
      of adverse events (AEs) [including dose-reduction and modification] is critical
      to achieving high levels of adherence to treatment. A team-focussed treatment
      strategy that includes patient counselling and follow-up can contribute to
      managing AEs to ensure successful continuation of sorafenib therapy. In addition,
      a proposed definition of unresponsiveness to transarterial chemoembolization and
      the implications of treatment lag on the outcomes of sorafenib therapy, as well
      as measures for the prevention and treatment of hand-foot skin reaction are
      discussed.

PMID- 22873626
TI  - Current status of hepatocellular carcinoma treatment in Japan: case study and
      discussion-voting system.
AB  - The Toward Integrated Treatment of Advanced Hepatocellular Carcinoma with Nexavar
      (TiTAN) Symposium was held in August 2010 in Tokyo, Japan, during which the
      position of sorafenib (Nexavar(r)) in the treatment of HCC in Japan (for which it
      received approval in 2009) was discussed by a panel of eight expert hepatologists
      in a session chaired by Dr Kudo. The following article focuses on the discussion
      that went on during this session, including question and answer sessions
      regarding the experiences of the 350 conference attendees in treating patients
      with HCC, as well as some of the more challenging disease management issues.
      Since 2008, when the phase III Sorafenib Hepatocellular Carcinoma Assessment
      Randomized Protocol (SHARP) trial demonstrated an increase in the median overall
      survival (OS) for patients with unresectable HCC treated with sorafenib compared
      with placebo, international and Japanese guidelines recommend sorafenib as a
      first-line option for patients with advanced HCC Child-Pugh liver function class
      A who have extrahepatic metastasis. Sorafenib is also recommended for patients
      unresponsive to transarterial chemoembolization (TACE) or hepatic arterial
      infusion chemotherapy (HAIC). Importantly, if HCC is judged to be unresponsive to
      TACE, treatment should be switched to sorafenib in a timely manner. Almost half
      of the conference attendees said that they used both the Japan Society of
      Hepatology clinical practice guidelines and the clinical practice guidelines for
      HCC when determining treatment strategies for individual HCC patients. Sorafenib
      should currently not be used as adjuvant therapy or in combination with TACE or
      HAIC until evidence from ongoing clinical trials shows that it is beneficial in
      these settings.

PMID- 22873627
TI  - Closing remarks.

PMID- 22873630
TI  - The application of bioisosteres in drug design for novel drug discovery: focusing
      on acid protease inhibitors.
AB  - INTRODUCTION: A bioisostere is a powerful concept for medicinal chemistry. It
      allows the improvement of the stability; oral absorption; membrane permeability;
      and absorption, distribution, metabolism and excretion (ADME) of drug candidate,
      while retaining their biological properties. The term 'bioisostere' is derived
      from 'isostere', whose physical and chemical properties, such as steric size,
      hydrophobicity, and electronegativity, are similar to those of a functional or
      atomic group, and is considered to possess biological properties. Here, the
      authors highlight the recent applications of bioisosteres in drug design, mainly
      based on our drug discovery studies. AREAS COVERED: This review discusses the
      application of bioisosteres for novel drug discovery with focus on the authors'
      drug discovery studies such as renin, HIV-protease, and beta-secretase
      inhibitors. The authors highlight that some bioisosteres can form the scaffolding
      for drug candidates, namely substrate transition state, amide/ester, and
      carboxylic acid bioisosteres. Moreover, the authors propose the new terms
      'electron-donor bioisostere' and 'conformational bioisostere' for drug discovery.
      EXPERT OPINION: The authors discuss the importance of bioisostere's design
      concept based on specific interaction with the corresponding biomolecule. In
      addition, some strategies for drug discovery based on the bioisostere concept are
      introduced. Many bioisosteres, which are recognized by corresponding target
      biomolecules as exhibiting similar biological properties, have been reported to
      date; most of the recently developed bioisosteres were designed by
      cheminformatics approaches. Some molecular design softwares and databases are
      introduced.

PMID- 22873631
TI  - Doping of vanadium to nanocrystalline diamond films by hot filament chemical
      vapor deposition.
AB  - Doping an impure element with a larger atomic volume into crystalline structure
      of buck crystals is normally blocked because the rigid crystalline structure
      could not tolerate a larger distortion. However, this difficulty may be weakened
      for nanocrystalline structures. Diamonds, as well as many semiconductors, have a
      difficulty in effective doping. Theoretical calculations carried out by DFT
      indicate that vanadium (V) is a dopant element for the n-type diamond
      semiconductor, and their several donor state levels are distributed between the
      conduction band and middle bandgap position in the V-doped band structure of
      diamond. Experimental investigation of doping vanadium into nanocrystalline
      diamond films (NDFs) was first attempted by hot filament chemical vapor
      deposition technique. Acetone/H2 gas mixtures and vanadium oxytripropoxide
      (VO(OCH2CH2CH3)3) solutions of acetone with V and C elemental ratios of 1:5,000,
      1:2,000, and 1:1,000 were used as carbon and vanadium sources, respectively. The
      resistivity of the V-doped NDFs decreased two orders with the increasing V/C
      ratios.

PMID- 22873632
TI  - Can vibroacoustic stimulation improve the efficiency of a tertiary care antenatal
      testing unit?
AB  - OBJECTIVE: Our primary objective was to determine whether vibroacoustic
      stimulation (VAS) decreases time to fetal reactivity in the antenatal testing
      unit (ATU) of a tertiary care center. METHODS: We performed a prospective,
      quality assurance initiative to determine whether VAS could increase the
      efficiency of our ATU. On pre-specified "VAS days," VAS was applied for 3 s, if
      the non-stress test was non-reactive in the first 10 min. Generalized estimating
      equations models were used to account for within subject correlation due to
      multiple appointments per patient. RESULTS: VAS use was associated with a 3.76
      min reduction in time to reactivity (21.79 vs 25.55, p = 0.011) and a 56%
      reduction in the need for a biophysical profile (OR: 0.44, 95% CI: 0.21-0.90).
      Overall, however, we found no significant decrease in time spent on the monitor
      or in the ATU. CONCLUSION: Compliance with a strict VAS protocol may improve the
      efficiency of increasingly busy ATUs.

PMID- 22873633
TI  - General Practitioners' responses to global climate change - lessons from clinical
      experience and the clinical method.
AB  - BACKGROUND: Climate change is a global public health problem that will require
      complex thinking if meaningful and effective solutions are to be achieved. In
      this conceptual paper we argue that GPs have much to bring to the issue of
      climate change from their wide-ranging clinical experience and from the
      principles underpinning their clinical methods. This experience and thinking
      calls forth particular contributions GPs can and should make to debate and
      action. DISCUSSION: We contend that the privileged experience and GP way of
      thinking can make valuable contributions when applied to climate change
      solutions. These include a lifetime of experience, reflection and epistemological
      application to first doing no harm, managing uncertainty, the ability to make
      necessary decisions while possessing incomplete information, an appreciation of
      complex adaptive systems, maintenance of homeostasis, vigilance for unintended
      consequences, and an appreciation of the importance of transdisciplinarity and
      interprofessionalism. SUMMARY: General practitioners have a long history of
      public health advocacy and in the case of climate change may bring a way of
      approaching complex human problems that could be applied to the dilemmas of
      climate change.

PMID- 22873634
TI  - Synthesis of homo- and heterofunctionalized glycoclusters and binding to
      Pseudomonas aeruginosa lectins PA-IL and PA-IIL.
AB  - Homo- and heterofunctionalized glycoclusters with galactose and/or fucose
      residues targeting both PA-IL and PA-IIL lectins of Pseudomonas aeruginosa were
      synthesized using "Click" chemistry and DNA chemistry. Their binding to lectins
      (separately or in a mixture) was studied using a DNA Directed Immobilization
      carbohydrate microarray. Homoglycoclusters bind selectively to their lectin while
      the heteroglycocluster binds simultaneously both lectins with a slight lower
      affinity.

PMID- 22873636
TI  - Decomposition of gamma-cyclotrimethylene trinitramine (gamma-RDX): relevance for
      shock wave initiation.
AB  - To elucidate the reactive behavior of RDX crystals at pressures and temperatures
      relevant to shock wave initiation, Raman spectroscopy and optical imaging were
      used to determine the pressure-temperature (P-T) stability and the decomposition
      of gamma-RDX, the high pressure phase of RDX. Experiments were performed on
      single crystals in a diamond anvil cell at pressures from 6 to 12 GPa and at
      temperatures up to 600 K. Evidence for the direct decomposition of gamma-RDX
      above 6 GPa, without the involvement of other phases, is provided. The upper
      limit of the P-T locus for the gamma-RDX thermal decomposition was determined. A
      refined P-T phase diagram of RDX is presented that includes the current findings
      for gamma-RDX. The static compression results are used to gain key insight into
      the shock initiation of RDX, including a determination of the RDX phase at
      decomposition and understanding the role of pressure and temperature in
      accelerating shock induced decomposition. This study has established the
      important role that gamma-RDX plays in decomposition of RDX under static and
      shock compression conditions; thus theoretical modeling of RDX decomposition at
      high pressures and temperatures needs to incorporate the gamma-phase response.

PMID- 22873635
TI  - Reinforcing outpatient medical student learning using brief computer tutorials:
      the Patient-Teacher-Tutorial sequence.
AB  - BACKGROUND: At present, what students read after an outpatient encounter is
      largely left up to them. Our objective was to evaluate the education efficacy of
      a clinical education model in which the student moves through a sequence that
      includes immediately reinforcing their learning using a specifically designed
      computer tutorial. METHODS: Prior to a 14-day Pediatric Emergency rotation,
      medical students completed pre-tests for two common pediatric topics: Oral
      Rehydration Solutions (ORS) and Fever Without Source (FWS). After encountering a
      patient with either FWS or a patient needing ORS, the student logged into a
      computer that randomly assigned them to either a) completing a relevant computer
      tutorial (e.g. FWS patient + FWS tutorial = "in sequence") or b) completing the
      non-relevant tutorial (e.g. FWS patient + ORS tutorial = "out of sequence"). At
      the end of their rotation, they were tested again on both topics. Our main
      outcome was post-test scores on a given tutorial topic, contrasted by whether
      done in- or out-of-sequence. RESULTS: Ninety-two students completed the study
      protocol with 41 in the 'in sequence' group. Pre-test scores did not differ
      significantly. Overall, doing a computer tutorial in sequence resulted in
      significantly greater post-test scores (z-score 1.1 (SD 0.70) in sequence vs.
      0.52 (1.1) out-of-sequence; 95% CI for difference +0.16, +0.93). Students spent
      longer on the tutorials when they were done in sequence (12.1 min (SD 7.3) vs.
      10.5 (6.5)) though the difference was not statistically significant (95% CI diff:
      -1.2 min, +4.5). CONCLUSIONS: Outpatient learning frameworks could be structured
      to take best advantage of the heightened learning potential created by patient
      encounters. We propose the Patient-Teacher-Tutorial sequence as a framework for
      organizing learning in outpatient clinical settings.

PMID- 22873637
TI  - Cocktail sedation containing propofol versus conventional sedation for ERCP: a
      prospective, randomized controlled study.
AB  - BACKGROUND: ERCP practically requires moderate to deep sedation controlled by a
      combination of benzodiazepine and opiod. Propofol as a sole agent may cause
      oversedation. A combination (cocktail) of infused propofol, meperidine, and
      midazolam can reduce the dosage of propofol and we hypothesized that it might
      decrease the risk of oversedation. We prospectively compare the efficacy,
      recovery time, patient satisfactory, and side effects between cocktail and
      conventional sedations in patients undergoing ERCP. METHODS: ERCP patients were
      randomized into 2 groups; the cocktail group (n = 103) and the controls (n =
      102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam
      were administered in both groups. In the cocktail group, a bolus dose of propofol
      1 mg/kg was administered and continuously infused. In the controls, 25 mg of
      meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of
      sedation. RESULTS: In the cocktail group, the average administration rate of
      propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of
      meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery
      times and patients' satisfaction scores in the cocktail and control groups were
      9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001),
      respectively. Desaturation rates in the cocktail and conventional groups were
      58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with
      temporary oxygen supplementation without the need for scope removal. CONCLUSIONS:
      Cocktail sedation containing propofol provides faster recovery time and better
      patients' satisfaction for patients undergoing ERCP. However, mild degree of
      desaturation may still develop. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01540084.

PMID- 22873638
TI  - Immune activation and CD127 expression on T lymphocyte subsets of a Chinese
      cohort of pediatric AIDS patients with different viral responses.
AB  - Immune activation and IL-7/IL7 receptor (CD127) systems are significant for CD4+
      T cell defect in AIDS patients. However, the association between immune
      activation and CD127 expression on T lymphocyte subsets in Chinese pediatric AIDS
      patients is not well studied. Here, we recruited a cohort of 194 Chinese
      pediatric AIDS patients: 135 good viral responders (GVRs) and 59 poor viral
      responders (PVRs). CD38high and HLA-DR+CD8+ T lymphocytes and CD127 expression on
      T-cell subsets were determined by flow cytometry. Viral load was detected using a
      quantitative RT-PCR assay. The results showed that pediatric AIDS patients had a
      lower memory CD4+ percentage and a higher memory CD8+ T-cell percentage. The
      percentage of naive CD4+T-cells was higher, especially in GVRs. The percentage of
      CD38high and HLA-DR+CD8+ in PVRs was higher than in GVRs and controls, being
      positively correlated with viral load and memory CD8+, but negatively correlated
      with memory CD4+ T cells. The percentage of CD127+ memory CD4+ T cells in GVRs
      was higher than in PVRs, but lower than in controls. CD127 expression was
      positively correlated with percentage of CD4+ subsets and naive CD8+ T cells, but
      negatively correlated with percentage of memory CD8+ T cells. Our study
      demonstrates that the percentages of CD38high and HLA-DR+ CD8+ T cells are good
      markers to evaluate immune activation of pediatric AIDS patients, and elevated
      immune activation has a more profound effect on memory T cells. IL- 7/CD127
      system is more important to maintain the proportion of naive T cells.

PMID- 22873640
TI  - Noninvasive surface coverage determination of chemically modified conical
      nanopores that rectify ion transport.
AB  - Surface modification will change the surface charge density (SCD) at the signal
      limiting region of nanochannel devices. By fitting the measured i-V curves in
      simulation via solving the Poisson and Nernst-Planck equations, the SCD and
      therefore the surface coverage can be noninvasively quantified. Amine terminated
      organosilanes are employed to chemically modify single conical nanopores.
      Determined by the protonation-deprotonation of the functional groups, the density
      and polarity of surface charges are adjusted by solution pH. The rectified
      current at high conductivity states is found to be proportional to the SCD near
      the nanopore orifice. This correlation allows the noninvasive determination of
      SCD and surface coverage of individual conical nanopores.

PMID- 22873639
TI  - Meningitis due to Cryptococcus neoformans: treatment with posaconazole.
AB  - BACKGROUND: Central nervous system infections caused by Cryptococcus neoformans
      remain to be opportunistic infections with high mortality in severely
      immunocompromised patients such as patients with AIDS. Amphotericin B
      deoxycholate and fluconazole remain to be the drugs of choice; however, in
      consideration of the intolerance to amphotericin B deoxycholate and the possible
      resistance to fluconazole, it is necessary to evaluate other azoles, such as
      posaconazole, that have demonstrated lower adverse events. The objective of this
      study was to describe the characteristics and clinical and microbiological
      response of the use of posaconazole in patients with CNS infections caused by C.
      neoformans. METHODS: We designed a case study that included eight patients
      diagnosed with AIDS and cryptococcal meningitis. Seven patients were treated with
      800 mg of posaconazole orally for 28 days. RESULTS: During the second week of
      treatment, a cerebrospinal fluid (CSF) culture was performed and was negative for
      the development of C. neoformans. The patients showed an improvement in signs and
      symptoms of impairment of the CNS such as reduction of cephalea, fever, visual
      disturbances such as double vision, meningism and papilledema, and improved
      alertness and environmental awareness. CONCLUSIONS: CNS fungal infections usually
      occur in immunocompromised patients. The use of systemic antifungal agents
      contributes to the development of fungal resistance. The results of this study
      suggest that posaconazole is a good alternative in the treatment of fungal CNS
      infection due to C. neoformans.

PMID- 22873641
TI  - Regulation of double-stranded RNA dependent protein kinase expression and
      attenuation of protein synthesis induced by bacterial toll-like receptors
      agonists in the absence of interferon.
AB  - Double-stranded RNA dependent protein kinase (PKR) is a host defense enzyme whose
      expression is up-regulated in response to interferons (IFNs) and during viral
      infections. Increased levels of PKR can result in its activation, which, in turn,
      inhibits global cellular protein synthesis. Despite growing evidence suggesting
      the involvement of PKR in bacterial infections, little is known about its
      expression, regulation and cellular role in nonviral infections. The aim of this
      work was to determine the expression and regulation of PKR in response to
      stimulation of human THP-1 monocytes with bacterial agonists of TLR2/4. Treatment
      of cells with Pam3CSK4 or lipopolyssacharide (LPS) resulted in an increase in PKR
      mRNA and protein levels. Robust PKR expression at later times correlated with a
      decrease in global protein synthesis. PKR was also required to regulate the
      inhibition of protein synthesis triggered by LPS in mouse splenocytes.
      Surprisingly, no increase of IFN-beta or IFN-alpha mRNA levels was detected after
      treatment of THP-1 cells with toll-like receptor (TLR) agonists. In accordance
      with this, the supernatants from LPS or Pam3CSK4-treated cells lacked the ability
      to activate the PKR and ISG56 promoters in gene reporter assays carried out in
      HEK293T cells. The expression of PKR induced by TLRs agonists was dramatically
      impaired when cells were treated in the presence of tosyl-phenylalanyl
      chloromethylketone or Mithramycin, suggesting that NF-kappaB and Sp1
      transcription factors, but not those activated by IFNs, regulate the expression
      of PKR in human monocytes.

PMID- 22873642
TI  - How much fluid resuscitation is optimal in septic shock?
AB  - Smith and Perner report an observational cohort study of 164 patients with septic
      shock. For patients still alive on day 3, higher compared with lower fluid volume
      resuscitation was associated with lower 90-day mortality. This association of a
      relationship between fluid intake and decreased mortality aligns with the
      randomized controlled trial of early goal-directed therapy and later
      observational studies. I suggest careful individualization of fluid resuscitation
      to achieve adequate mean arterial pressure (about 60 to 70 mmHg) and
      normalization of arterial lactate levels in septic shock. 

PMID- 22873644
TI  - Multicomponent NAPL source dissolution: evaluation of mass-transfer coefficients.
AB  - Mass transfer rate coefficients were quantified by employing an inverse modeling
      technique to high-resolution aqueous phase concentration data observed following
      an experimental release of a multicomponent nonaqueous phase liquid (NAPL) at a
      field site. A solute transport model (SEAM3D) was employed to simulate advective
      dispersive transport over time coupled to NAPL dissolution. Model calibration was
      demonstrated by accurately reproducing the observed breakthrough times and peak
      concentrations at multiple observation points, observed mass discharge at pumping
      wells, and the reported mass depletions for three soluble NAPL constituents.
      Vertically variable NAPL mass transfer coefficients were derived for each
      constituent using an optimized numerical solute transport model, ranging from
      0.082 to 2.0 day(-1) across all constituents. Constituent-specific coefficients
      showed a positive correlation with liquid-phase diffusion coefficients.
      Application of a time-varying mass transfer coefficient as NAPL mass depleted
      showed limited sensitivity during which over 80% of the most soluble NAPL
      constituent dissolved from the source. Long-term simulation results, calibrated
      to the experimental data and rendered in terms of mass discharge versus source
      mass depletion, exhibited multistage behavior.

PMID- 22873643
TI  - Raising the speed limit for beta-hairpin formation.
AB  - Understanding the folding of the beta-hairpin is a crucial step in studying how
      beta-rich proteins fold. We have studied CLN025, an optimized ten residue
      synthetic peptide, which adopts a compact, well-structured beta-hairpin
      conformation. Formation of the component beta-sheet and beta-turn structures of
      CLN025 was probed independently using a combination of equilibrium Fourier
      transform infrared spectroscopy and laser-induced temperature jump coupled with
      time-resolved infrared and fluorescence spectroscopies. We find that CLN025 is an
      ultrafast folder due to its small free energy barrier to folding and that it
      exceeds the predicted speed limit for beta-hairpin formation by an order of
      magnitude. We also find that the folding mechanism cannot be described by a
      simple two-state model, but rather is a heterogeneous process involving two
      independent parallel processes. Formation of stabilizing cross-strand hydrophobic
      interactions and turn alignment occur competitively, with relaxation lifetimes of
      82 +/- 10 and 124 +/- 10 ns, respectively, at the highest probed temperature. The
      ultrafast and heterogeneous folding kinetics observed for CLN025 provide evidence
      for folding on a nearly barrierless free energy landscape, and recalibrate the
      speed limit for the formation of a beta-hairpin.

PMID- 22873645
TI  - Cell-permeable gomesin peptide promotes cell death by intracellular Ca(2+)
      overload.
AB  - In recent years, the antitumoral activity of antimicrobial peptides (AMPs) has
      been the goal of many research studies. Among AMPs, gomesin (Gm) displays
      antitumor activity by unknown mechanisms. Herein, we studied the cytotoxicity of
      Gm in the Chinese hamster ovary (CHO) cell line. Furthermore, we investigated the
      temporal ordering of organelle changes and the dynamics of Ca(2+) signaling
      during Gm-induced cell death. The results indicated that Gm binds to the plasma
      membrane and rapidly translocates into the cytoplasm. Moreover, 20 MUM Gm
      increases the cytosolic Ca(2+) and induces  membrane permeabilization after 30
      min of treatment. Direct Ca(2+) measurements in CHO cells transfected with the
      genetically encoded D1-cameleon to the endoplasmic reticulum (ER) revealed that
      Gm induces ER Ca(2+) depletion, which in turn resulted in oscillatory
      mitochondrial Ca(2+) signal, as measured in cells expressing the genetically
      encoded probe to the mitochondrial matrix (mit)Pericam. This leads to
      mitochondria disruption, loss of mitochondrial membrane potential and increased
      reactive oxygen species prior to membrane permeabilization. Gm-induced membrane
      permeabilization by a Ca(2+)-dependent pathway involving Gm translocation into
      the cell, ER Ca(2+) depletion and disruption, mitochondrial Ca(2+) overload and
      oxidative stress.

PMID- 22873646
TI  - Laser-induced inactivation of Plasmodium falciparum.
AB  - BACKGROUND: Haemozoin crystals, produced by Plasmodium during its intra
      erythrocytic asexual reproduction cycle, can generate UV light via the laser
      induced, non-linear optical process of third harmonic generation (THG). In the
      current study the feasibility of using haemozoin, constitutively stored in the
      parasite's food vacuole, to kill the parasite by irradiation with a near IR laser
      was evaluated. METHODS: Cultured Plasmodium parasites at different stages of
      development were irradiated with a pulsed NIR laser and the viability of
      parasites at each stage was evaluated from their corresponding growth curves
      using the continuous culture method. Additional testing for germicidal effects of
      haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to
      Escherichia coli in suspension. Cell suspensions were then irradiated with the
      laser and small aliquots taken and spread on agar plates containing selective
      agents to determine cell viability (CFU). RESULTS: Parasites in the late
      trophozoites form as well as trophozoites in early-stage of DNA synthesis were
      found to be the most sensitive to the treatment with -4-log reduction in
      viability after six passes through the laser beam; followed by parasites in ring
      phase (-2-log reduction). A -1-log reduction in E. coli viability was obtained
      following a 60 min irradiation regimen of the bacteria in the presence of 1 MUM
      synthetic haemozoin and a -2-log reduction in the presence of 10 MUM haemozoin.
      Minimal (<= 15%) cell kill was observed in the presence of 10 MUM haemin.
      CONCLUSIONS: Laser-induced third-harmonic generation by haemozoin can be used to
      inactivate Plasmodium. This result may have clinical implications for treating
      severe malaria symptoms by irradiating the patient's blood through the skin or
      through dialysis tubing with a NIR laser.

PMID- 22873648
TI  - Abnormal conductivity behavior in porous lead telluride films.
AB  - We report the experimental observation of the novel phenomenon of the
      resistivity decrease in porous PbTe layers during the pore formation process.
      Investigations were performed on the n-PbTe films with 2.3-MUm thickness, which
      were near the point of the conductivity-type inversion at room temperature.
      Anodic electrochemical treatment for the porous layers with 41% to 52% porosity
      fabrication was performed using a KOH-based Norr electrolyte solution. For the
      porous lead telluride layers, the resistivity value at 300 K decreased 2.5 to 3
      times. For the explanation of the observed phenomenon, a physical model is
      proposed which takes into account the Pb/Te ratio change during the anodic
      treatment.

PMID- 22873647
TI  - HSULF-1 inhibits ERK and AKT signaling and decreases cell viability in vitro in
      human lung epithelial cells.
AB  - BACKGROUND: Heparan sulfate proteoglycans (HSPGs) modulate the binding and
      activation of signaling pathways of specific growth factors, such as fibroblast
      growth factor-2 (FGF-2). Human endosulfatase 1 (HSULF-1) is an enzyme that
      selectively removes 6-O sulfate groups from HS side chains and alter their level
      and pattern of sulfation and thus biological activity. It is known that HSULF-1
      is expressed at low levels in some cancer cell lines and its enhanced expression
      can inhibit cancer cell growth or induce apoptosis, but the mechanism(s) involved
      has not been identified. METHODS: HSULF-1 mRNA expression was assessed in five
      normal cells (primary human lung alveolar type 2 (hAT2) cells, adult lung
      fibroblasts (16Lu), fetal lung fibroblasts (HFL), human bronchial epithelial
      cells (HBE), and primary human lung fibroblasts (HLF)) and five lung cancer cell
      lines (A549, H292, H1975, H661, and H1703) using quantitative real time
      polymerase chain reaction (qRT-PCR). H292 and hAT2 cells over-expressing HSULF-1
      were analyzed for cell viability, apoptosis, and ERK/Akt signaling, by MTT (3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, TUNEL
      (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, and Western
      Blot, respectively. Apoptosis pathway activation was confirmed by PCR array in
      hAT2, H292, and A549 cells. RESULTS: HSULF-1 was expressed at a significantly
      lower level in epithelial cancer cell lines compared to normal cells. Infection
      with recombinant adenovirus for HSULF-1 over-expression resulted in decreased
      cell viability in H292 cells, but not in normal hAT2 cells. HSULF-1 over
      expression induced apoptosis in H292 cells, but not in hAT2 cells. In addition,
      apoptosis pathways were activated in both H292 and A549 cells, but not in hAT2
      cells. HSULF-1 over-expression reduced ERK and Akt signaling activation in H292
      cells, which further demonstrated its inhibitory effects on signaling related to
      proliferation. CONCLUSIONS: These results indicate that HSULF-1 is expressed at
      lower levels in H292 lung cancer cells than in normal human alveolar cells and
      that its over-expression reduced cell viability in H292 cells by inducing
      apoptotic pathways, at least in part by inhibiting ERK/Akt signaling. We
      hypothesize that HSULF-1 plays important roles in cancer cells and functions to
      modify cell signaling, inhibit cancer proliferation, and promote cancer cell
      death.

PMID- 22873649
TI  - Lower mortality following coronary arterial revascularization in patients taking
      statins.
AB  - OBJECTIVES: Numerous studies have suggested that statins have beneficial non
      lipid-lowering effects, including reduction of systemic inflammatory response
      following surgery. We wanted to evaluate the effect of preoperative statin
      treatment on complications and operative mortality after coronary arterial
      revascularization. DESIGN: We performed a retrospective study of 720 consecutive
      patients who underwent on-pump coronary artery bypass grafting (CABG) (n = 513)
      or off-pump (OPCAB) (n = 207) in Iceland from 2002-2006. Patients taking statins
      preoperatively (n = 529) were compared with those not taking statins (n = 191).
      Predictors of complications and operative mortality were evaluated by univariate
      and multivariate analysis. RESULTS: Cardiovascular risk profiles were similar.
      However, hypertension was more common in the statin group but EuroSCORE was
      slightly lower. Operative mortality was significantly lower in patients taking
      statins (1.7% vs. 5.8%, p < 0.001). There were no significant differences in the
      incidence of major complications. Multivariate analysis showed that preoperative
      statin treatment was an independent predictor of lower operative mortality (OR =
      0.33, p = 0.043), even after adjusting for EuroSCORE, acute operations, advanced
      age, or other medications. CONCLUSIONS: In this non- randomized study, patients
      taking statins had lower operative mortality than the controls after adjusting
      for multiple confounders. The reason for this might be linked to pleiotropic
      effects of statins.

PMID- 22873650
TI  - A stereoselective approach to beta-L-arabino nucleoside analogues: synthesis and
      cyclization of acyclic 1',2'-syn N,O-acetals.
AB  - Reported herein is a novel and versatile strategy for the stereoselective
      synthesis of unnatural beta-L-arabinofuranosyl nucleoside analogues from acyclic
      N,OTMS-acetals bearing pyrimidine and purine bases. These unusual acetals undergo
      a C1' to C4' cyclization where the OTMS of the acetal serves as the nucleophile
      to generate 2'-oxynucleosides with complete retention of configuration at the C1'
      acetal center. N,OTMS-acetals are obtained diastereoselectively from additions of
      silylated nucleobases onto acyclic polyalkoxyaldehydes in the presence of
      MgBr(2).OEt(2). The strategy reported is addressing important synthetic
      challenges by providing stereoselective access to unnatural L-nucleosides
      starting from easily accessible pools of D-sugars and, as importantly, by
      allowing the formation of the sterically challenging 1',2'-cis nucleosides. A
      wide variety of nucleoside analogues were synthesized in 7-8 steps from easily
      accessible D-xylose.

PMID- 22873652
TI  - Quality assessment of systematic reviews on short dental implants.
AB  - BACKGROUND: Critical analysis of published systematic reviews may help in
      understanding their strengths and weaknesses and identifying areas that need
      improvement. Short dental implants are becoming an important addition to the
      existing dental armamentarium. The aim of this overview is to analyze the quality
      of published systematic reviews focused on short dental implants using
      established checklists such as the assessment of multiple systematic reviews
      (AMSTAR). METHODS: A search was conducted to retrieve reviews that used a
      systematic approach in article selection focusing on short dental implants in
      humans. Based on a set of inclusion and exclusion criteria, a total of 10 reviews
      were selected. Two independent reviewers appraised the quality of the selected
      reviews using AMSTAR and the checklist proposed by Glenny et al. in 2003. Each
      article was given a total score based on the number of criteria that it
      fulfilled. RESULTS: Six reviews satisfied <=4 of the 11 AMSTAR items, and only
      two reviews satisfied nine of the 11 items. This study shows that published
      systematic reviews on short dental implants exhibit significant structural and
      methodological variability. Quality assessment using the Glenny checklist further
      confirmed the variability in the way systematic reviews were conducted and/or
      reported. A high correlation was observed between the two checklists' scores.
      CONCLUSIONS: Uniformity in the way systematic reviews are conducted and/or
      reported will increase the validity and clinical applicability of future reviews.

PMID- 22873651
TI  - Interaction between cytokine gene polymorphisms and the effect of physical
      exercise on clinical and inflammatory parameters in older women: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Aging is associated with chronic low-grade inflammatory activity with
      an elevation of cytokine levels. An association between regular physical activity
      and reduction of blood levels of anti-inflammatory cytokines is demonstrated in
      the literature pointing to an anti-inflammatory effect related to exercise.
      However, there is no consensus regarding which type of exercise and which
      parameters are the most appropriate to influence inflammatory markers. Evidence
      indicates that the single nucleotide polymorphism (SNP) can influence the
      synthesis of those cytokines affecting their production. METHODS/DESIGN: The
      design of this study is a randomized controlled trial. The aim of this study is
      to investigate the interaction between the cytokine genes SNP and the effect of
      physical activity on older women. The main outcomes are: serum levels of sTNFR-1,
      sTNFR-2, interleukin (IL)-6, IL-10, measured by the ELISA method; genotyping of
      tumor necrosis factor- (TNF)-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896)
      by the TaqMan Method (Applied Biosystems, Foster City, CA, USA); and physical
      performance assessed by Timed Up and Go and 10-Meter Walk Tests. Secondary
      outcomes include: Geriatric Depression Scale, Perceived Stress Scaleand aerobic
      capacity, assessed by the six-minute walk; and lower limb muscle strength, using
      an isokinetic dinamometer (Biodex Medical Systems, Inc., Shirley, NY,USA). Both
      exercise protocols will be performed three times a week for 10 weeks, 30 sessions
      in total. DISCUSSION: Investigating the interaction between genetic factors and
      exercise effects of both protocols of exercise on the levels of inflammatory
      cytokine levels can contribute to guide clinical practice related to treatment
      and prevention of functional changes due to chronic inflammatory activity in
      older adults. This approach could develop new perspectives on preventive and
      treatment proposals in physical therapy and in the management of the older
      patient. TRIAL REGISTRATION: (ReBEC) RBR9v9cwf.

PMID- 22873653
TI  - Change of periodontal disease status during and after pregnancy.
AB  - BACKGROUND: This study explored whether there is any change of periodontal
      disease status during and after pregnancy. We also examined whether the change is
      different between females with a history of gestational diabetes mellitus (GDM)
      and females without GDM during pregnancy. METHODS: A follow-up study was
      conducted at Woman's Hospital, Baton Rouge, Louisiana. Thirty-nine females who
      were previously enrolled in a case-control study during pregnancy were followed
      an average of 22 months postpartum. Periodontal status was assessed through
      dental examinations performed both during and after pregnancy. Clinical
      periodontal parameters included bleeding on probing (BOP), mean probing depth
      (PD), and mean clinical attachment level (CAL). Periodontitis was defined as the
      presence of >=1 sites exhibiting PD >=4 mm or CAL >=4 mm. We used generalized
      estimating equation analysis to examine the change of periodontal status.
      RESULTS: Mean number and percentage of sites with BOP decreased from 10.7 +/-
      11.6 (mean +/- SD) and 6.5% +/- 7.0% during pregnancy to 7.1 +/- 8.8 and 4.3% +/-
      5.3% at 22 months postpartum (P <0.05), respectively. Mean levels of PD and CAL
      decreased from 1.8 +/- 0.4 mm and 1.9 +/- 0.3 mm to 1.6 +/- 0.3 mm and 1.6 +/-
      0.3 mm (P <0.01), respectively. The prevalence of periodontitis decreased from
      66.7% to 33.3% (P <0.01, adjusted risk ratio = 2.1, 95% confidence interval = 1.3
      to 3.4). There was no difference in the change of periodontal status between
      females with GDM and females without GDM during pregnancy. CONCLUSIONS: Pregnancy
      may be associated with an increased risk of periodontal disease. The association
      is not different between females with GDM and females without GDM during
      pregnancy.

PMID- 22873654
TI  - Effects of estrogen deficiency and/or caffeine intake on alveolar bone loss,
      density, and healing: a study in rats.
AB  - BACKGROUND: The aim of this study is to evaluate the effects of caffeine and/or
      estrogen deficiency on ligature-induced bone loss (BL), trabecular bone area
      (TBA), and postextraction bone healing (BH). METHODS: Rats were assigned into one
      of the following groups (15 each): 1) control = non-ingestion of caffeine/sham
      surgery; 2) caffeine = ingestion of caffeine/sham surgery); 3) ovariectomized
      (OVX) = non-ingestion of caffeine/ovariectomy; or 4) caffeine/OVX = ingestion of
      caffeine/ovariectomy. The rats were under caffeine administration for 65 days
      and/or estrogen deficiency for 51 days. On day 21 after ovariectomy, one first
      mandibular molar received a ligature and the contralateral tooth was not ligated.
      The first maxillary molars were extracted 8 days before sacrifice. BL, TBA, the
      positive cells for tartrate-resistant acid phosphatase (TRAP), receptor activator
      of nuclear factor-kappaB ligand (RANKL), and osteoprotegerin (OPG) were analyzed
      in the furcation area of mandibular molars. Histometric BH and gene expression of
      bone morphogenetic protein (BMP)-2, BMP-7, osteopontin, and bone sialoprotein
      were evaluated in alveolar sockets. RESULTS: The caffeine group presented the
      greatest BL and the OVX group the highest number of TRAP-positive (TRAP(+)) cells
      around ligated teeth (P <0.05). The control group presented higher TBA and BH
      than the other groups (P <0.05). All test groups presented higher RANKL/OPG(+)
      cells than the control group around ligated/unligated teeth. The OVX and
      caffeine/OVX groups presented a greater number of TRAP(+) cells around unligated
      teeth than the control group (P <0.05). There were no differences among groups
      for gene expression (P >0.05). CONCLUSIONS: Caffeine increased BL in ligated
      teeth. Caffeine and/or estrogen deficiency decreased TBA in the unligated teeth
      and reduced BH after tooth extraction.

PMID- 22873655
TI  - Soft-tissue alterations following exposure to tooth-whitening agents.
AB  - BACKGROUND: Tooth-whitening agents are widely used, either as self-application
      products or under the supervision of a dentist. These products may be associated
      with transient gross morphologic changes in oral soft tissues. However, their
      potential effects on human keratinocytes and fibroblasts in a stratified squamous
      epithelium have yet to be elucidated. METHODS: In this study, three-dimensional
      human tissue equivalents are exposed to varying concentrations of tooth-whitening
      agents for increasing time periods. Tissue alterations are investigated in terms
      of morphology, proliferation, apoptosis, and protein expression. RESULTS: All
      whitening agents tested altered tissue morphology, induced proliferation of basal
      keratinocytes, and caused apoptosis of cells in all epithelial strata. In
      addition, whitening agents induced alterations in the expression of cytokines
      that are linked to inflammation. CONCLUSIONS: These results suggest that
      whitening agents may induce similar changes in vivo and that these products
      should be used for limited periods of time or under the supervision of a dental
      professional.

PMID- 22873656
TI  - Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter
      actinomycetemcomitans-associated periodontitis? Double-masked, randomized
      clinical trial of efficacy and safety.
AB  - BACKGROUND: It has been suggested that prescription of amoxicillin plus
      metronidazole in the context of periodontal therapy should be limited to patients
      with specific microbiologic profiles, especially those testing positive for
      Aggregatibacter actinomycetemcomitans. The main purpose of this analysis is to
      determine if patients positive for A. actinomycetemcomitans with moderate to
      advanced periodontitis benefit specifically from amoxicillin plus metronidazole
      given as an adjunct to full-mouth scaling and root planing. METHODS: This is a
      double-masked, placebo-controlled, randomized longitudinal study including 41
      participants who were positive for A. actinomycetemcomitans and 41 participants
      who were negative for A. actinomycetemcomitans. All 82 patients received full
      mouth periodontal debridement performed within 48 hours. Patients then received
      either systemic antibiotics (375 mg amoxicillin and 500 mg metronidazole, three
      times daily) or placebo for 7 days. The primary outcome variable was persistence
      of sites with a probing depth (PD) >4 mm and bleeding on probing (BOP) at the 3
      month reevaluation. Using multilevel logistic regression, the effect of the
      antibiotics was analyzed according to the following factors (interaction effect):
      A. actinomycetemcomitans-positive or -negative at baseline, sex, age, smoking,
      tooth being a molar, and interdental location. RESULTS: At reevaluation,
      participants in the test group had significantly fewer sites with a persisting PD
      >4 mm and BOP than control patients (P <0.01). Being A. actinomycetemcomitans
      positive or -negative did not change the effect of the antibiotics. Patients
      benefited from the antibiotics irrespective of sex, age, or smoking status.
      Molars benefited significantly more from the antibiotics than non-molars (P for
      interaction effect = 0.03). CONCLUSIONS: Patients who were positive for A.
      actinomycetemcomitans had no specific benefit from amoxicillin plus
      metronidazole. Sites on molars benefited significantly more from the antibiotics
      than non-molar sites.

PMID- 22873657
TI  - Ten-year results following treatment of intrabony defects with an enamel matrix
      protein derivative combined with either a natural bone mineral or a beta
      tricalcium phosphate.
AB  - BACKGROUND: The purpose of the present study is to evaluate the 10-year results
      following treatment of intrabony defects treated with an enamel matrix protein
      derivative (EMD) combined with either a natural bone mineral (NBM) or beta
      tricalcium phosphate (beta-TCP). METHODS: Twenty-two patients with advanced
      chronic periodontitis and displaying one deep intrabony defect were randomly
      treated with a combination of either EMD + NBM or EMD + beta-TCP. Clinical
      evaluations were performed at baseline and at 1 and 10 years. The following
      parameters were evaluated: plaque index, bleeding on probing, probing depth,
      gingival recession, and clinical attachment level (CAL). The primary outcome
      variable was CAL. RESULTS: The defects treated with EMD + NBM demonstrated a mean
      CAL change from 8.9 +/- 1.5 mm to 5.3 +/- 0.9 mm (P <0.001) and to 5.8 +/- 1.1 mm
      (P <0.001) at 1 and 10 years, respectively. The sites treated with EMD + beta-TCP
      showed a mean CAL change from 9.1 +/- 1.6 mm to 5.4 +/- 1.1 mm (P <0.001) at 1
      year and 6.1 +/- 1.4 mm (P <0.001) at 10 years. At 10 years two defects in the
      EMD + NBM group had lost 2 mm, whereas two other defects had lost 1 mm of the CAL
      gained at 1 year. In the EMD + beta-TCP group three defects had lost 2 mm,
      whereas two other defects had lost 1 mm of the CAL gained at 1 year. Compared
      with baseline, at 10 years, a CAL gain of >=3 mm was measured in 64% (i.e., seven
      of 11) of the defects in the EMD + NBM group and in 82% (i.e., nine of 11) of the
      defects in the EMD + beta-TCP group. No statistically significant differences
      were found between the 1- and 10-year values in either of the two groups. Between
      the treatment groups, no statistically significant differences in any of the
      investigated parameters were observed at 1 and 10 years. CONCLUSION: Within their
      limitations, the present findings indicate that the clinical improvements
      obtained with regenerative surgery using EMD + NBM or EMD + beta-TCP can be
      maintained over a period of 10 years.

PMID- 22873658
TI  - Benefits of using magnesium sulphate (MgSO4) for eclampsia management and
      maternal mortality reduction: lessons from Kano State in Northern Nigeria.
AB  - BACKGROUND: Despite clear emphasis through the Millennium Development Goals, the
      problem of high maternal mortality persists especially within low and middle
      income countries. Various studies report remarkably high maternal mortality rates
      in northern Nigeria, where maternal mortality rates exceed 1,000 deaths per
      100,000 live births and eclampsia contributes approximately 40% of maternal
      deaths. Across Nigeria, diazepam is routinely used for the management of
      eclampsia. Prior to February 2008, diazepam was widely used for the management of
      eclampsia in Kano State (within northern Nigeria) with case fatality rate being
      over 20%. While magnesium sulphate (MgSO4) is recognized as the most effective
      drug for the management of eclampsia; this study aims to compare MgSO4 therapy
      with diazepam therapy in terms of case fatality rates and costs. FINDINGS: This
      retrospective study, including 1045 patients with eclampsia and pre-eclampsia
      during the years 2008 and 2009, reports a drop in case fatality rates from 20.9%
      (95% CI: 18.7, 23.2) to 2.3% (95% CI: 1.4, 3.2) among eclampsia patients
      following the MgSO4 intervention. The study observed no significant difference in
      the cost of using MgSO4 therapy compared to diazepam therapy. CONCLUSIONS: The
      study found a remarkable reduction in case fatality rate due to eclampsia in
      those who received MgSO4 therapy with minimal increase in costs when compared to
      diazepam therapy. Concerted efforts should be focused on properly introducing
      MgSO4 into emergency obstetric protocols especially within developing countries
      to reduce maternal mortality and also impact on health system performance.

PMID- 22873659
TI  - Editorial: "Fluorescent probes: from bench to bedside".

PMID- 22873660
TI  - Ligands for fluorescence correlation spectroscopy on g protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) comprise a large protein family of
      transmembrane receptors involved in many physiological processes. They are
      engaged in various transduction processes of extracellular signals into
      intracellular responses. Due to their involvement in numerous diseases they
      represent an important pharmacological target. Fluorescence correlation
      spectroscopy (FCS) poses a very sensitive analytical technique well-suited for
      the investigation of GPCRs. It is minimally invasive and operates on a single
      molecular level. It further provides detailed pharmacological information on
      receptor kinetics and quantities of activated receptors on the cell membrane. In
      addition, FCS allows distinguishing between different receptor states based on
      different diffusion time constants. In order to be applicable for FCS, the
      molecule of interest has to be fluorescently labeled. This review focuses on the
      physical requirements for dyes intended for FCS, their influence on the binding
      characteristics of coupled ligands and strategies to generate dye labeled
      ligands, exemplified on GPCR ligands.

PMID- 22873661
TI  - Activatable fluorescent probes: a new concept in optical molecular imaging.
AB  - Activatable fluorescent probes share the unique feature of being turned on only
      under specific conditions: they are "silent" when not interacting with a specific
      target protein, microenvironment, or reactive species. Several activatable
      fluorescence probes have demonstrated their potential in cell biology study,
      disease study and diagnosis, and even in the rapidly expanding field of image
      guided surgery. In this review, we will summarize progress in the design of
      activatable probes and their application in studying cell biology or in optical
      imaging. Some of the most effective examples of activatable fluorescent probes
      will be presented and their application will be discussed.

PMID- 22873662
TI  - Recent advances in optical cancer imaging of EGF receptors.
AB  - Epidermal growth factor (EGF) receptors are commonly expressed on the cell
      membrane of cancer cells and activity of these receptors results in accelerated
      cell growth and carcinogenesis. A variety of targeted molecules have been
      developed to block ligand binding and/or inhibit the function of these receptor
      tyrosine kinases, and several have proven therapeutic benefits. Along with the
      advent of new therapeutic agents comes a need for non-invasive tools to diagnose,
      characterize, and monitor tumor responsiveness to therapy. Imaging EGF receptors
      with radionuclides has been performed for decades. However, recently this area
      has advanced considerably with the development of EGF receptor-targeted optical
      imaging probes. Herein, we review recent advances in molecular imaging of the EGF
      receptor family, focusing specifically on optical imaging. Such agents provide
      the opportunity for earlier diagnosis, improved tumor characterization, and the
      ability to measure and monitor tumor responsiveness to anti-EGF receptor
      treatment strategies.

PMID- 22873663
TI  - Recent advances in receptor-targeted fluorescent probes for in vivo cancer
      imaging.
AB  - Receptor-targeted optical imaging of cancer is emerging as an attractive strategy
      for early cancer diagnosis and surgical guidance. The success of such strategy
      depends largely upon the development of receptor-targeted fluorescent probes with
      high specificity and binding affinity to the target receptors. Recently, a host
      of such probes have been reported to target cancer-specific receptors, such as
      somatostatin receptors (SSTRs), integrin receptors, cholecystokinin-2 (CCK(2))
      receptor, gastrin-releasing peptide (GRP) receptor, endothelin A (ET(A))
      receptor, translocator protein (TSPO) receptor, epidermal growth factor (EGF)
      receptor, human epidermal growth factor receptor 2 (HER2), vascular endothelial
      growth factor (VEGF) receptor, folate receptor (FR), transferrin receptor (TFR),
      low-density lipoprotein (LDL) receptors, type I insulin-like growth factor
      receptor (IGF1R), vasoactive intestinal peptide (VIP) receptors, urokinase
      plasminogen activator (uPA) and estrogen receptor (ER). This review will describe
      the recent advances in synthetic targeting optical imaging probes and demonstrate
      their in vivo imaging potentials. Moreover, current status of near infrared (NIR)
      fluorescent dyes, targeting moieties and coupling reactions, as well as
      strategies for designing targeted probes, will also be discussed.

PMID- 22873664
TI  - Noninvasive fluorescence imaging in animal models of stroke.
AB  - Noninvasive fluorescence imaging (NFI) is a powerful tool to study physiology and
      pathophysiology in animal disease models. NFI has been successfully applied in a
      number of animal disease models including cancer, arthritis, and stroke.
      Furthermore, several applications in humans have been described. NFI is widely
      available in research laboratories because it has a number of advantages: It uses
      non-ionizing radiation and requires comparably simple, inexpensive
      instrumentation, and easy to handle. Fluorochromes can be detected with high
      sensitivity, and image acquisition time is relatively short. Furthermore, a
      plethora of fluorescent imaging agents is available including unspecific, target
      specific, and activatable imaging probes. With these probes, biological processes
      such as inflammation, cell death or enzyme activity, and many others can be
      visualized in living animals. This review offers an overview of current
      approaches in NFI of stroke pathophysiology in animal models of cerebral
      ischemia. First, the instrumentation and the different types of imaging agents
      for NFI are described. Second, a short introduction to animal models of stroke is
      provided. Third, examples for NFI in animal models of stroke are given. Finally,
      the use of NFI in human stroke is critically discussed.

PMID- 22873665
TI  - Near infrared receptor-targeted nanoprobes for early diagnosis of cancers.
AB  - The success of detecting cancer at early stages relies greatly on the sensitivity
      and specificity of in vivo molecular imaging. Optical imaging with near infrared
      (NIR) luminescent molecular nanoprobes currently attracts much attention because
      of many advantages of this imaging modality. It provides real time imaging with
      relatively inexpensive cost, produces images with high sensitivity and spatial
      resolution, and avoids exposure to ionizing irradiation. Raman
      spectroscopy/microscopy imaging with surface enhanced Raman scattering (SERS)
      nanoparticles allows scientists to detect biological events in living cells or
      organisms in real time and with high sensitivity. The photoacoustic imaging has
      emerged as a hybrid of optical and ultrasound imaging for sensitive and
      quantitative tumor detection. Given the recent advances in nanoscience and
      biomedicine, receptor-targeted NIR nanoprobes promise to improve the cancer early
      detection with relatively high sensitivity and specificity. We summarize various
      targeted NIR nanoprobes and their potential applications in cancer targeting and
      in vivo imaging and discuss the potential of multimodality imaging of NIR
      nanoprobes. With ongoing efforts to enhance their targeting ability and endow
      more functions, NIR nanoprobes hold great promise for clinical translation.

PMID- 22873666
TI  - In-vitro assessment of a new portable ballistic lithotripter with percutaneous
      and ureteroscopic models.
AB  - BACKGROUND AND PURPOSE: The EMS Swiss LithoBreaker is a new, portable,
      electrokinetic lithotripter. We compared its tip velocity and displacement
      characteristics with a handheld, pneumatic lithotripter LMA StoneBreaker.TM We
      also evaluated fragmentation efficiency using in vitro models of percutaneous and
      ureteroscopic stone fragmentation. MATERIALS AND METHODS: Displacement and
      velocity profiles were measured for 1-mm and 2-mm probes using a laser beam aimed
      at a photo detector. For the percutaneous model, 2-mm probes fragmented 10-mm
      spherical BegoStone phantoms until the fragments passed through a 4-mm mesh
      sieve. The ureteroscopic model used 1-mm probes and compared the pneumatic and
      electrokinetic devices to a 200-MUm holmium laser fiber. Cylindrical (4-mm
      diameter, 4-mm length) BegoStone phantoms were placed into silicone tubing to
      simulate the ureter; fragmented stones passed through a narrowing in the tubing.
      RESULTS: For both 1-mm and 2-mm probes, the electrokinetic device had
      significantly higher tip displacement and slower tip velocity, P<0.01. In the
      percutaneous model, the electrokinetic device needed an average of 484 impulses
      over 430 seconds to fragment one BegoStone, while the pneumatic device needed 29
      impulses over 122 seconds to fragment one stone. Both clearance times and number
      of impulses needed for percutaneous stone clearance were significantly different
      at P<0.01. Ureteroscopically, the mean clearance time was 97 seconds for the
      electrokinetic lithotripter, 145 seconds for the pneumatic lithotripter, and 304
      seconds for the laser. Comparing the pneumatic device with the electrokinetic
      device ureteroscopically, there was no significant difference in clearance time,
      P=0.55. Both the pneumatic and electrokinetic lithotripters, however,
      demonstrated decreased clearance times compared with the laser, P=0.027.
      CONCLUSIONS: The portable electrokinetic lithotripter may be better suited for
      ureteroscopy instead of percutaneous nephrolithotomy. It appears to be comparable
      to the portable pneumatic device in the ureter. Further clinical studies are
      needed to confirm these findings in vivo.

PMID- 22873669
TI  - A high-affinity gold-binding camel antibody: antibody engineering for one-pot
      functionalization of gold nanoparticles as biointerface molecules.
AB  - Antibodies, with their high affinity and specificity, are widely utilized in the
      field of protein engineering, medicinal chemistry, and nanotechnology
      applications, and our recent studies have demonstrated the recognition and
      binding of antibody for the surface on inorganic material. In this study, we
      generated a high-affinity gold-binding antibody fragment by a combination of
      peptide-grafting and phage-display techniques and showed the availability of the
      material-binding fragment for one-pot functionalization of nanoparticles as
      interface molecules. After a gold-binding peptide sequence was grafted into one
      of the complementarity determining regions of a single variable domain of a heavy
      chain camel antibody, a combinatorial library approach raised by 20 times the
      affinity of the peptide-grafted fragment. The high-affinity gold-binding fragment
      (E32) spontaneously adsorbed on gold nanoparticles, and consequently the
      nanoparticles formed a stable dispersion in a high-ionic-strength solution.
      Multivalent and bispecific antibodies constructed on the E32 platform by means of
      fusion technology functionalized gold nanoparticles in one pot, and these
      functionalized nanoparticles could be used to obtain surface plasmon resonance
      scattering images of cancer cells and to spontaneously link two different
      nanomaterials. Here, we propose the bispecific antibodies as convenient interface
      molecules in the nanosized world.

PMID- 22873667
TI  - Influence of breaching the connective sheaths of the donor nerve on its
      myelinated sensory axons and on their sprouting into the end-to-side coapted
      nerve in the rat.
AB  - The influence of breaching the connective sheaths of the donor sural nerve on
      axonal sprouting into the end-to-side coapted peroneal nerve was examined in the
      rat. In parallel, the effect of these procedures on the donor nerve was assessed.
      The sheaths of the donor nerve at the coaptation site were either left completely
      intact (group A) or they were breached by epineurial sutures (group B), an
      epineurial window (group C), or a perineurial window (group D). In group A, the
      compound action potential (CAP) of sensory axons was detected in ~10% and 40% of
      the recipient nerves at 4 and 8 weeks, respectively, which was significantly less
      frequently than in group D at both recovery periods. In addition, the number of
      myelinated axons in the recipient nerve was significantly larger in group D than
      in other groups at 4 weeks. At 8 weeks, the number of axons in group A was only
      ~15% of the axon numbers in other groups (p<0.05). Focal subepineurial
      degenerative changes in the donor nerves were only seen after 4 weeks, but not
      later. The average CAP area and the total number of myelinated axons in the donor
      nerves were not different among the experimental groups. In conclusion,
      myelinated sensory axons are able to penetrate the epiperineurium of donor nerves
      after end-to-side nerve coaption; however, their ingrowth into recipient nerves
      is significantly enhanced by breaching the epiperineurial sheets at the
      coaptation site. Breaching does not cause permanent injury to the donor nerve.

PMID- 22873668
TI  - Medical students' attitudes toward gay men.
AB  - BACKGROUND: Healthcare providers' attitudes toward sexual minorities influence
      patient comfort and outcomes. This study characterized medical student attitudes
      toward gay men, focusing on behavior, personhood, gay civil rights, and male
      toughness. METHODS: A cross-sectional web-based anonymous survey was sent to
      medical students enrolled at the University of California, Davis (N = 371) with a
      response rate of 68%. RESULTS: Few respondents expressed negative attitudes
      toward gay men or would deny them civil rights. More negative responses were seen
      with respect to aspects of intimate behavior and homosexuality as a natural form
      of sexual expression. Men and students younger than 25 years old were more likely
      to endorse negative attitudes toward behavior as well as more traditional views
      on male toughness. CONCLUSIONS: We show that an important minority of students
      express discomfort with the behavior of gay men and hold to a narrow construction
      of male identity. These findings suggest that competency training must move
      beyond conceptual discussions and address attitudes toward behaviors through new
      pedagogical approaches.

PMID- 22873670
TI  - The 8th AIMS Conference on Dynamical Systems, Differential Equations and
      Applications.

PMID- 22873671
TI  - Stability analysis of multi-compartment models for cell production systems.
AB  - We study two- and three-compartment models of a hierarchical cell production
      system with cell division regulated by the level of mature cells. We investigate
      the structure of equilibria with respect to parameters as well as local stability
      properties for the equilibria. To interpret the results we adapt the concept of
      reproduction numbers, which is well known in ecology, to stem cell population
      dynamics. In the two-compartment model, the positive equilibrium is stable
      wherever it exists. In the three-compartment model, we find that the intermediate
      stage of differentiation is responsible for the emergence of an instability
      region in the parameter plane. Moreover, we prove that this region shrinks as the
      mortality rate for mature cells increases and discuss this result.

PMID- 22873672
TI  - Passing to the limit 2D-1D in a model for metastatic growth.
AB  - We prove the convergence of a family of solutions to a two-dimensional transport
      equation with a non-local boundary condition modelling the evolution of a
      population of metastases. We show that when the data of the repartition along the
      boundary tend to a Dirac mass, then the solution of the associated problem
      converges and we derive a simple expression for the limit in terms of the
      solution of a 1D equation. This result permits us to improve the computational
      time needed to simulate the model.

PMID- 22873673
TI  - Classical solutions and steady states of an attraction-repulsion chemotaxis in
      one dimension.
AB  - We establish the existence of global classical solutions and non-trivial steady
      states of a one-dimensional attraction-repulsion chemotaxis model subject to the
      Neumann boundary conditions. The results are derived based on the method of
      energy estimates and the phase plane analysis.

PMID- 22873674
TI  - Stationary solutions to a system of size-structured populations with nonlinear
      growth rate.
AB  - We study stationary solutions to a system of size-structured population models
      with nonlinear growth rate. Several characterizations of stationary solutions are
      provided. It is shown that the steady-state problem can be converted into
      different problems such as two types of eigenvalue problems and a fixed-point
      problem. In the two-species case, we give an existence result of nonzero
      stationary solutions by using the fixed-point problem.

PMID- 22873675
TI  - Density-dependent quiescence in glioma invasion: instability in a simple reaction
      diffusion model for the migration/proliferation dichotomy.
AB  - Gliomas are very aggressive brain tumours, in which tumour cells gain the ability
      to penetrate the surrounding normal tissue. The invasion mechanisms of this type
      of tumour remain to be elucidated. Our work is motivated by the
      migration/proliferation dichotomy (go-or-grow) hypothesis, i.e. the antagonistic
      migratory and proliferating cellular behaviours in a cell population, which may
      play a central role in these tumours. In this paper, we formulate a simple go-or
      grow model to investigate the dynamics of a population of glioma cells for which
      the switch from a migratory to a proliferating phenotype (and vice versa) depends
      on the local cell density. The model consists of two reaction-diffusion equations
      describing cell migration, proliferation and a phenotypic switch. We use a
      combination of numerical and analytical techniques to characterize the
      development of spatio-temporal instabilities and travelling wave solutions
      generated by our model. We demonstrate that the density-dependent go-or-grow
      mechanism can produce complex dynamics similar to those associated with tumour
      heterogeneity and invasion.

PMID- 22873676
TI  - A mathematical model for the spread of Strepotococcus pneumoniae with
      transmission dependent on serotype.
AB  - We examine a mathematical model for the transmission of Streptococcus Pneumoniae
      amongst young children when the carriage transmission coefficient depends on the
      serotype. Carriage means pneumococcal colonization. There are two sequence types
      (STs) spreading in a population each of which can be expressed as one of two
      serotypes. We derive the differential equation model for the carriage spread and
      perform an equilibrium and global stability analysis on it. A key parameter is
      the effective reproduction number R (e). For R (e) <= 1,  there is only the
      carriage-free equilibrium (CFE) and the carriage will die out whatever be the
      starting values. For R (e) > 1, unless the effective reproduction numbers of the
      two STs are equal, in addition to the CFE there are two carriage equilibria, one
      for each ST. If the ST with the largest effective reproduction number is
      initially present, then in the long-term the carriage will tend to the
      corresponding equilibrium.

PMID- 22873677
TI  - Self-propelled micro-swimmers in a Brinkman fluid.
AB  - We prove an existence, uniqueness, and regularity result for the motion of a self
      propelled micro-swimmer in a particulate viscous medium, modelled as a Brinkman
      fluid. A suitable functional setting is introduced to solve the Brinkman system
      for the velocity field and the pressure of the fluid by variational techniques.
      The equations of motion are written by imposing a self-propulsion constraint,
      thus allowing the viscous forces and torques to be the only ones acting on the
      swimmer. From an infinite-dimensional control on the shape of the swimmer, a
      system of six ordinary differential equations for the spatial position and the
      orientation of the swimmer is obtained. This is dealt with standard techniques
      for ordinary differential equations, once the coefficients are proved to be
      measurable and bounded. The main result turns out to extend an analogous result
      previously obtained for the Stokes system.

PMID- 22873678
TI  - A mathematical model for cell cycle-specific cancer virotherapy.
AB  - Oncolytic viruses preferentially infect and replicate in cancerous cells, leading
      to elimination of tumour populations, while sparing most healthy cells. Here, we
      study the cell cycle-specific activity of viruses such as vesicular stomatitis
      virus (VSV). In spite of its capacity as a robust cytolytic agent, VSV cannot
      effectively attack certain tumour cell types during the quiescent, or resting,
      phase of the cell cycle. In an effort to understand the interplay between the
      time course of the cell cycle and the specificity of VSV, we develop a
      mathematical model for cycle-specific virus therapeutics. We incorporate the
      minimum biologically required time spent in the non-quiescent cell cycle phases
      using systems of differential equations with incorporated time delays. Through
      analysis and simulation of the model, we describe how varying the minimum cycling
      time and the parameters that govern viral dynamics affect the stability of the
      cancer-free equilibrium, which represents therapeutic success.

PMID- 22873679
TI  - Immediate in vivo target-specific cancer cell death after near infrared
      photoimmunotherapy.
AB  - BACKGROUND: Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer
      treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700)
      conjugate. In vitro cancer-specific cell death occurs during NIR light exposure
      in cells previously incubated with mAb-IR700 conjugates. However, documenting
      rapid cell death in vivo is more difficult. METHODS: A luciferase-transfected
      breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was
      produced and used for both in vitro and in vivo experiments for monitoring the
      cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up
      to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral
      MDA-MB-468luc tumors in female athymic mice, which subsequently received a
      panitumumab-IR700 conjugate in vivo. One side was used as a control, while the
      other was treated with NIR light of dose ranging from 50 to 150 J/cm2.
      Bioluminescence imaging (BLI) was performed before and after PIT. RESULTS: Dose
      dependent cell killing and regrowth was successfully monitored by the BLI signal
      in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95%
      immediately after PIT in vivo when light intensity was high (>100 J/cm2),
      however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with
      gradually increasing BLI signal. CONCLUSION: PIT induced massive cell death of
      targeted tumor cells immediately after exposure of NIR light that was
      demonstrated with BLI in vivo.

PMID- 22873680
TI  - Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive
      disorder: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Several small studies have shown beneficial effects of ondansetron, a
      serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive
      disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients
      with OCD is still unclear. Granisetron does not alter cytochrome P450 activity
      and might have a lower risk of drug interactions, a longer duration of action and
      a better tolerability profile than other 5-HT(3) receptor antagonists. OBJECTIVE:
      The objective of this study was to assess the efficacy and tolerability of
      granisetron augmentation of fluvoxamine in patients with OCD. STUDY DESIGN: This
      was a two-centre, randomized, double-blind, placebo-controlled, parallel-group
      study conducted from November 2011 to March 2012. STUDY SETTING: The study
      setting was outpatient clinics of two large referral centres. PATIENTS: Study
      participants were men and women, aged 18-60 years, who met the diagnostic
      criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) score of at least 21. INTERVENTIONS: Participants were
      randomly assigned to granisetron (Kytril((r)); SmithKline Beecham, Philadelphia,
      PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine
      for 8 weeks. MAIN OUTCOME MEASURE: Patients were assessed using the Y-BOCS at
      baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was
      the difference in the score change of Y-BOCS total score from baseline to week 8
      between the two groups. We also compared changes in the obsession and compulsion
      subscales of the Y-BOCS, and frequencies of partial response (>=25% reduction in
      Y-BOCS score), complete response (>=35% reduction in Y-BOCS score) and remission
      (Y-BOCS score <=16) between the two groups. RESULTS: Of the 42 included patients,
      39 (20 in the placebo group, 19 in the granisetron group) completed the study.
      Significant time X treatment interaction was observed for total Y-BOCS (F [2.097,
      79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and
      compulsion (F [2.050, 77.899] = 4.674, p = 0.012) subscales. By week 8, complete
      response and remission were achieved by 20 (100%) and 18 (90%) patients in the
      granisetron group and by 7 (35%) patients in the placebo group (p-value of
      Fisher's exact test <0.001, risk ratio (RR) [95% CI] = 3.857 [2.039, 7.297]).
      There was no significant difference in the tolerability between the two regimens.
      CONCLUSION: Granisetron is an efficacious adjunct for the short-term treatment of
      patients with moderate to severe OCD and is well tolerated. CLINICAL TRIAL
      REGISTRATION NUMBER: IRCT201202041556N32.

PMID- 22873681
TI  - Risk assessment in sepsis: a new prognostication rule by APACHE II score and
      serum soluble urokinase plasminogen activator receptor.
AB  - INTRODUCTION: Early risk assessment is the mainstay of management of patients
      with sepsis. APACHE II is the gold standard prognostic stratification system. A
      prediction rule that aimed to improve prognostication by APACHE II with the
      application of serum suPAR (soluble urokinase plasminogen activator receptor) is
      developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis
      including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum
      suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent
      assay; in 367 patients sequential measurements were performed. After ROC analysis
      and multivariate logistic regression analysis a prediction rule for risk was
      developed. The rule was validated in a double-blind fashion by an independent
      confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic
      shock patients, from Sweden. RESULTS: Serum suPAR remained stable within
      survivors and non-survivors for 10 days. Regression analysis showed that APACHE
      II >= 17 and suPAR >= 12 ng/ml were independently associated with unfavorable
      outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12
      ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR >= 12 ng/ml with
      mortality 17.4%; iii) APACHE II >= 17 and suPAR <12 ng/ml with mortality 37.4%;
      and iv) APACHE II >= 17 and suPAR >= 12 ng/ml with mortality 51.7%. This
      prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel
      prediction rule with four levels of risk in sepsis based on APACHE II score and
      serum suPAR is proposed. Prognostication by this rule is confirmed by an
      independent cohort.

PMID- 22873683
TI  - Neutral loss fragmentation pattern based screening for arginine-rich natural
      products in Xenorhabdus and Photorhabdus.
AB  - Although sharing a certain degree of structural uniformity, natural product
      classes exhibit variable functionalities such as different amino acid or acyl
      residues. During collision induced dissociation, some natural products exhibit a
      conserved fragmentation pattern close to the precursor ion. The observed
      fragments result from a shared set of neutral losses, creating a unique
      fragmentation pattern, which can be used as a fingerprint for members of these
      natural product classes. The culture supernatants of 69 strains of the
      entomopathogenic bacteria Photorhabdus and Xenorhabdus were analyzed by MALDI
      MS(2), and a database comprising MS(2) data from each strain was established.
      This database was scanned for concordant fragmentation patterns of different
      compounds using a customized software, focusing on relative mass differences of
      the fragment ions to their precursor ion. A novel group of related natural
      products comprising 25 different arginine-rich peptides from 16 different strains
      was identified due to its characteristic neutral loss fragmentation pattern, and
      the structures of eight compounds were elucidated. Two biosynthesis gene clusters
      encoding nonribosomal peptide synthetases were identified, emphasizing the
      possibility to identify a group of structurally and biosynthetically related
      natural products based on their neutral loss fragmentation pattern.

PMID- 22873684
TI  - Reactivity of Mount Simon sandstone and the Eau Claire shale under CO2 storage
      conditions.
AB  - The Mount Simon sandstone and Eau Claire shale formations are target storage and
      cap rock formations for the Illinois Basin-Decatur Geologic Carbon Sequestration
      Project. We reacted rock samples with brine and supercritical CO(2) at 51 
      degrees C and 19.5 MPa to access the reactivity of these formations at storage
      conditions and to address the applicability of using published kinetic and
      thermodynamic constants to predict geochemical alteration that may occur during
      storage by quantifying parameter uncertainty against experimental data.
      Incongruent dissolution of iron-rich clays and formation of secondary clays and
      amorphous silica will dominate geochemical alterations at this CO(2) storage site
      in CO(2)-rich brines. The surrogate iron-rich clay in the model required
      significant adjustments to its thermodynamic constants and inclusion of
      incongruent reaction terms to capture the change in solution composition under
      acid CO(2) conditions. This result emphasizes the need for experiments that
      constrain the conceptual geochemical model, calibrate mean parameter values, and
      quantify parameter uncertainty in reactive-transport simulations that will be
      used to estimate long-term CO(2) trapping mechanisms and changes in porosity and
      permeability.

PMID- 22873682
TI  - Weight change in control group participants in behavioural weight loss
      interventions: a systematic review and meta-regression study.
AB  - BACKGROUND: Unanticipated control group improvements have been observed in
      intervention trials targeting various health behaviours. This phenomenon has not
      been studied in the context of behavioural weight loss intervention trials. The
      purpose of this study is to conduct a systematic review and meta-regression of
      behavioural weight loss interventions to quantify control group weight change,
      and relate the size of this effect to specific trial and sample characteristics.
      METHODS: Database searches identified reports of intervention trials meeting the
      inclusion criteria. Data on control group weight change and possible explanatory
      factors were abstracted and analysed descriptively and quantitatively. RESULTS:
      85 trials were reviewed and 72 were included in the meta-regression. While there
      was no change in control group weight, control groups receiving usual care lost 1
      kg more than control groups that received no intervention, beyond measurement.
      CONCLUSIONS: There are several possible explanations why control group changes
      occur in intervention trials targeting other behaviours, but not for weight loss.
      Control group participation may prevent weight gain, although more research is
      needed to confirm this hypothesis.

PMID- 22873685
TI  - General rules for selective growth of enriched semiconducting single walled
      carbon nanotubes with water vapor as in situ etchant.
AB  - The presence of metallic nanotubes in as-grown single walled carbon nanotubes
      (SWNTs) is the major bottleneck for their applications in field-effect
      transistors. Herein, we present a method to synthesize enriched, semiconducting
      nanotube arrays on quartz substrate. It was discovered that introducing
      appropriate amounts of water could effectively remove the metallic nanotubes and
      significantly enhance the density of SWNT arrays. More importantly, we proposed
      and confirmed that the high growth selectivity originates from the etching effect
      of water and the difference in the chemical reactivities of metallic and
      semiconducting nanotubes. Three important rules were summarized for achieving a
      high selectivity in growing semiconducting nanotubes by systematically
      investigating the relationship among water concentration, carbon feeding rate,
      and the percentage of semiconducting nanotubes in the produced SWNT arrays.
      Furthermore, these three rules can be applied to the growth of random SWNT
      networks on silicon wafers.

PMID- 22873686
TI  - DNA-directed immobilization of horseradish peroxidase onto porous SiO2 optical
      transducers.
AB  - Multifunctional porous Si nanostructure is designed to optically monitor
      enzymatic activity of horseradish peroxidase. First, an oxidized PSi optical
      nanostructure, a Fabry-Perot thin film, is synthesized and is used as the optical
      transducer element. Immobilization of the enzyme onto the nanostructure is
      performed through DNA-directed immobilization. Preliminary studies demonstrate
      high enzymatic activity levels of the immobilized horseradish peroxidase, while
      maintaining its specificity. The catalytic activity of the enzymes immobilized
      within the porous nanostructure is monitored in real time by reflective
      interferometric Fourier transform spectroscopy. We show that we can easily
      regenerate the surface for consecutive biosensing analysis by mild
      dehybridization conditions.

PMID- 22873688
TI  - Identification of a promising drug candidate for the treatment of type 2 diabetes
      based on a P2Y(1) receptor agonist.
AB  - The activation by extracellular nucleotides of pancreatic P2Y receptors,
      particularly, the P2Y(1)R subtype, increases insulin secretion. Therefore, we
      developed analogues of the P2Y(1)R receptor agonist 2-MeS-ADP, as potential
      antidiabetic drugs. Analogue 3A was found to be a potent P2Y(1)R agonist (EC(50)
      = 0.038 MUM vs 0.0025 MUM for 2-MeS-ADP) showing no activity at P2Y(2/4/6)Rs.
      Analogue 3A was stable at pH 1.4 (t(1/2) = 7.3 h) and resistant to hydrolysis vs
      2-MeS-ADP by alkaline phosphatase (t(1/2) = 6 vs 4.5 h), human e-NPP1 (4% vs 16%
      hydrolysis after 20 min), and human blood serum (30% vs 50% hydrolysis after 24
      h). Intravenous administration of 3A in naive rats decreased blood glucose from
      155 mg/dL to normal values, ca. 87 mg/dL, unlike glibenclamide, leading to
      subnormal values (i.e., 63 mg/dL). Similar observations were made for
      streptozotocin (STZ)-treated and db(+)/db(-) mouse models. Furthermore, 3A
      inhibits platelet aggregation in vitro and elongates bleeding time in mice (iv
      administration of 30 mg of 3A/kg), increasing bleeding time to 16 vs 9 min for
      Prasugrel. Oral administration of 30 mg/kg 3A to rats increased tail bleeding
      volume, similar to aspirin. These findings suggest that 3A may be an effective
      treatment for type 2 diabetes by reducing both blood glucose levels and platelet
      aggregation.

PMID- 22873687
TI  - Allicin enhances host pro-inflammatory immune responses and protects against
      acute murine malaria infection.
AB  - BACKGROUND: During malaria infection, multiple pro-inflammatory mediators
      including IFN-gamma, TNF and nitric oxide (NO) play a crucial role in the
      protection against the parasites. Modulation of host immunity is an important
      strategy to improve the outcome of malaria infection. Allicin is the major
      biologically active component of garlic and shows anti-microbial activity.
      Allicin is also active against protozoan parasites including Plasmodium, which is
      thought to be mediated by inhibiting cysteine proteases. In this study, the
      immunomodulatory activities of allicin were assessed during acute malaria
      infection using a rodent malaria model Plasmodium yoelii 17XL. METHODS: To
      determine whether allicin modulates host immune responses against malaria
      infection, mice were treated with allicin after infection with P. yoelii 17XL.
      Mortality was checked daily and parasitaemia was determined every other day. Pro
      inflammatory mediators and IL-4 were quantified by ELISA, while NO level was
      determined by the Griess method. The populations of dendritic cells (DCs),
      macrophages, CD4+ T and regulatory T cells (Treg) were assessed by FACS. RESULTS:
      Allicin reduced parasitaemia and prolonged survival of the host in a dose
      dependent manner. This effect is at least partially due to improved host immune
      responses. Results showed that allicin treatment enhanced the production of pro
      inflammatory mediators such as IFN-gamma, TNF, IL-12p70 and NO. The absolute
      numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin
      treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas
      it did not cause major changes in IL-4 and the level of anti-inflammatory
      cytokine IL-10. CONCLUSIONS: Allicin could partially protect host against P.
      yoelii 17XL through enhancement of the host innate and adaptive immune responses.

PMID- 22873689
TI  - Electrical stimulation: a novel tool for tissue engineering.
AB  - New advances in tissue engineering are being made through the application of
      different types of electrical stimuli to influence cell proliferation and
      differentiation. Developments made in the last decade have allowed us to improve
      the structure and functionality of tissue-engineered products through the use of
      growth factors, hormones, drugs, physical stimuli, bioreactor use, and two
      dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices
      (with various material properties and topography). Another potential type of
      stimulus is electricity, which is important in the physiology and development of
      the majority of all human tissues. Despite its great potential, its role in
      tissue regeneration and its ability to influence cell migration, orientation,
      proliferation, and differentiation has rarely been considered in tissue
      engineering. This review highlights the importance of endogenous electrical
      stimulation, gathering the current knowledge on its natural occurrence and role
      in vivo, discussing the novel methods of delivering this stimulus and examining
      its cellular and tissue level effects, while evaluating how the technique could
      benefit the tissue engineering discipline in the future.

PMID- 22873690
TI  - Proposal for a method to estimate nutrient shock effects in bacteria.
AB  - BACKGROUND: Plating methods are still the golden standard in microbiology;
      however, some studies have shown that these techniques can underestimate the
      microbial concentrations and diversity. A nutrient shock is one of the mechanisms
      proposed to explain this phenomenon. In this study, a tentative method to assess
      nutrient shock effects was tested. FINDINGS: To estimate the extent of nutrient
      shock effects, two strains isolated from tap water (Sphingomonas capsulata and
      Methylobacterium sp.) and two culture collection strains (E. coli CECT 434 and
      Pseudomonas fluorescens ATCC 13525) were exposed both to low and high nutrient
      conditions for different times and then placed in low nutrient medium (R2A) and
      rich nutrient medium (TSA).The average improvement (A.I.) of recovery between R2A
      and TSA for the different times was calculated to more simply assess the
      difference obtained in culturability between each medium. As expected, A.I. was
      higher when cells were plated after the exposition to water than when they were
      recovered from high-nutrient medium showing the existence of a nutrient shock for
      the diverse bacteria used. S. capsulata was the species most affected by this
      phenomenon. CONCLUSIONS: This work provides a method to consistently determine
      the extent of nutrient shock effects on different microorganisms and hence
      quantify the ability of each species to deal with sudden increases in substrate
      concentration.

PMID- 22873691
TI  - A novel scale to assess resistance-exercise effort.
AB  - In this study, we examined the validity of a novel subjective scale for assessing
      resistance-exercise effort. Seventeen male bodybuilders performed five sets of 10
      repetitions at 70% of one-repetition maximum, for the bench press and squat. At
      the completion of each set, participants quantified their effort via the rating
      of perceived exertion (RPE) and novel estimated-repetitions-to-failure scales,
      and continued repetitions to volitional exhaustion to determine actual
      repetitions-to-failure. There were high correlations between estimated- and
      actual-repetitions-to-failure across sets for the bench press and squat (r >=
      0.93; P < 0.05). During sets 3, 4, and 5, estimated-repetitions-to-failure
      predicted the number of repetitions to failure for the bench press and squat, as
      indicated by smaller effect sizes for differences (ES = 0.37-0.0). The estimated
      repetitions-to-failure scale was reliable as indicated by high intraclass
      correlation coefficients (>=0.92) and narrow 95% limits of agreement (<=0.63
      repetitions) for both the bench press and squat. Despite high correlations
      between RPE and actual-repetitions-to-failure (P < 0.05), RPE at volitional
      fatigue was less than maximal for both exercises. Our results suggest that the
      estimated-repetitions-to-failure scale is valid for predicting onset of muscular
      failure, and can be used for the assessment and prescription of resistance
      exercise.

PMID- 22873693
TI  - Sanitation facilities in Kampala slums, Uganda: users' satisfaction and
      determinant factors.
AB  - Access to improved sanitation is a key preventive measure against sanitary
      related gastro-enteric diseases such as diarrhoea. We assessed the access to
      sanitation facilities and users' satisfaction in 50 randomly selected slums of
      Kampala through a cross-sectional survey conducted in 2010. A total of 1500
      household respondents were interviewed. Sixty-eight per cent of the respondents
      used shared toilets, 20% private, 11% public toilets and less than 1% reported
      using flying toilets or practising open defecation. More than half of the
      respondents (51.7%) were not satisfied with their sanitation facilities.
      Determinants for satisfaction with the facilities used included the nature and
      type of toilet facilities used, their cleanliness, and the number of families
      sharing them. The study findings showed that slum dwellers had high access to
      sanitation facilities. However, most of them were shared and majority of the
      respondents were not satisfied with their facilities, primarily due to
      cleanliness and over demand.

PMID- 22873692
TI  - Minor activities and transition state properties of the human steroid
      hydroxylases cytochromes P450c17 and P450c21, from reactions observed with
      deuterium-labeled substrates.
AB  - The steroid hydroxylases CYP17A1 (P450c17, 17-hydroxylase/17,20-lyase) and
      CYP21A2 (P450c21, 21-hydroxylase) catalyze progesterone hydroxylation at one or
      more sites within a 2 A radius. We probed their hydrogen atom abstraction
      mechanisms and regiochemical plasticity with deuterium-labeled substrates: 17
      [(2)H]-pregnenolone; 17-[(2)H]-, 16alpha-[(2)H]-, 21,21,21-[(2)H(3)]-, and 21
      [(2)H]-progesterone; and 21,21,21-[(2)H(3)]-17-hydroxyprogesterone. Product
      distribution and formation rates with recombinant human P450-oxidoreductase and
      wild-type human CYP17A1 or mutation A105L (reduced progesterone 16alpha
      hydroxylation) and wild-type human CYP21A2 or mutation V359A (substantial
      progesterone 16alpha-hydroxylation) were used to calculate intramolecular and
      intermolecular kinetic isotope effects (KIEs). The intramolecular KIEs for
      CYP17A1 and mutation A105L were 4.1 and 3.8, respectively, at H-17 and 2.9 and
      5.1, respectively, at H-16alpha. Mutation A105L 21-hydroxylates progesterone (5%
      of products), and wild-type CYP17A1 also catalyzes a trace of 21-hydroxylation,
      which increases with 16alpha-[(2)H]- and 17-[(2)H]-progesterone. The
      intramolecular KIEs with CYP21A2 mutation V359A and progesterone were 6.2 and 3.8
      at H-21 and H-16alpha, respectively. Wild-type CYP21A2 also forms a trace of
      16alpha-hydroxyprogesterone, which increased with 21,21,21-[(2)H(3)]-progesterone
      substrate. Competitive intermolecular KIEs paralleled the intramolecular KIE
      values, with (D)V values of 1.4-5.1 and (D)V/K values of 1.8-5.1 for these
      reactions. CYP17A1 and CYP21A2 mutation V359A both 16alpha-hydroxylate 16alpha
      [(2)H]-progesterone with 33-44% deuterium retention, indicating stereochemical
      inversion. We conclude that human CYP17A1 has progesterone 21-hydroxylase
      activity and human CYP21A2 has progesterone 16alpha-hydroxylase activity, both of
      which are enhanced with deuterated substrates. The transition states for C-H bond
      cleavage in these hydroxylation reactions are either significantly nonlinear
      and/or asymmetric, and C-H bond breakage is partially rate-limiting for all
      reactions.

PMID- 22873694
TI  - Impact of laparoscopic experience on the proficiency gain of urologic surgeons in
      robot-assisted surgery.
AB  - PURPOSE: The aim of our study is to assess the impact of skill in laparoscopic
      surgery on the learning of robot-assisted surgery by urologic surgeons using the
      Mimic dV-trainer (MdVT). MATERIALS AND METHODS: Twenty-three urologic surgeons
      using the MdVT were assessed. Ten of them were laparoscopic surgeons certified by
      the Japanese Society of Endourology. Each of the subjects completed four trials
      of a program consisting of four EndoWrist modules and two needle-driving modules.
      The performances of all subjects were recorded using a built-in scoring
      algorithm. RESULTS: In only one of the needle-driving tasks, Suture Sponge (that
      all subjects felt was the most difficult task), the scores of the certified
      laparoscopic surgeons became significantly better than those of the other
      subjects at the 2nd and the 3rd trials (p=0.0236 and p=0.0043 at the 2nd and 3rd
      trials, respectively). At the 4th trial there was no significant difference
      between the two groups with regard to the overall scores of any tasks.
      CONCLUSIONS: Our data indicate that familiarity with laparoscopic surgery is not
      associated with any advantage in learning the most fundamental techniques of
      robot-assisted surgery.

PMID- 22873695
TI  - Evaluating the consistency of gene sets used in the analysis of bacterial gene
      expression data.
AB  - BACKGROUND: Statistical analyses of whole genome expression data require
      functional information about genes in order to yield meaningful biological
      conclusions. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) are common sources of functionally grouped gene sets. For bacteria, the
      SEED and MicrobesOnline provide alternative, complementary sources of gene sets.
      To date, no comprehensive evaluation of the data obtained from these resources
      has been performed. RESULTS: We define a series of gene set consistency metrics
      directly related to the most common classes of statistical analyses for gene
      expression data, and then perform a comprehensive analysis of 3581 Affymetrix(r)
      gene expression arrays across 17 diverse bacteria. We find that gene sets
      obtained from GO and KEGG demonstrate lower consistency than those obtained from
      the SEED and MicrobesOnline, regardless of gene set size. CONCLUSIONS: Despite
      the widespread use of GO and KEGG gene sets in bacterial gene expression data
      analysis, the SEED and MicrobesOnline provide more consistent sets for a wide
      variety of statistical analyses. Increased use of the SEED and MicrobesOnline
      gene sets in the analysis of bacterial gene expression data may improve
      statistical power and utility of expression data.

PMID- 22873696
TI  - Identification of genetic defects underlying FVII deficiency in 10 patients
      belonging to eight unrelated families of the North provinces from Tunisia.
AB  - Inherited factor VII (FVII) deficiency is a rare disorder characterized by a
      bleeding phenotype varying from mild to severe. To date, more than 200 mutations
      have been described along the F7 gene encoding for FVII. The aim of this study
      was the identification of genetic defects underlying FVII deficiency in 10
      patients belonging to eight unrelated families of the North provinces from
      Tunisia. Mutation detection was performed by sequencing the whole F7 gene coding
      region, exon-intron boundaries and about 400 bp of the promoter region. We
      identified 5 mutations in five unrelated families; the novel p.F328Y mutation and
      the reported mutations: p.R304Q, p.M298I, IVS1aG > A and p.G-39G. For the
      remaining 5 patients we didn't identified any mutations using PCR/Sequencing
      protocol. In conclusion, this study represents the first comprehensive molecular
      series of FVII deficiency affected patients in Tunisia from the North. We will
      try in the future to continue the molecular study for Tunisian patients from
      Center and South provinces in order to have a complete idea about the FVII
      deficiency mutational profile in our country. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1288044089753085.

PMID- 22873697
TI  - Characterization of carotenoid aggregates by steady-state optical spectroscopy.
AB  - The carotenoids have low-lying triplet excited states and can self-assemble in
      some solvents to form weakly or strongly coupled aggregates. These qualities make
      carotenoid aggregates useful for studies of singlet fission, where an outstanding
      goal is the correlation of interchromophoric coupling to the dynamics and yield
      of triplet excited states from a parent singlet excited state. Three aggregates
      of zeaxanthin, two weakly coupled and one strongly coupled, are characterized by
      steady-state spectroscopic methods including temperature-dependent absorption,
      fluorescence, and resonance Raman spectroscopy. The absorption spectra for each
      type of aggregate are distinct; however, an analysis of band positions reveals
      some important shared characteristics and suggests that the strongly coupled H
      aggregate contains a subpopulation of weakly coupled constituents. Temperature
      dependent absorption spectroscopy indicates that one of the weakly coupled
      aggregates can be converted to the other upon heating. The emission spectra of
      the three aggregates have similar profiles that are overall red-shifted by more
      than 1000 cm(-1) relative to the monomer. The emission quantum yields of the
      aggregates are 5 to 30 times less than that of the monomer, with the lowest yield
      for the strongly coupled aggregate. The vibrational spectra of the chromophores
      support only slight perturbations from the structure of solvated monomers. Our
      findings support the conclusion that all three aggregates are best characterized
      as H-aggregates, in agreement with a prior theoretical study of lutein
      aggregates.

PMID- 22873698
TI  - Medical students' choices of specialty in The Gambia: the need for career
      counseling.
AB  - BACKGROUND: Understanding preferences for specialties by medical students and the
      factors driving choices assists policy makers in ensuring optimal spread of
      personnel across disciplines. METHODS: This cross-sectional survey using self
      administered structured questionnaires was conducted on consenting students of
      the first medical school in The Gambia, established in 1999. Data collection was
      in June/July 2011. Questions were on sociodemographic characteristics of
      students, their parents, factors related to career preferences and opinions about
      counseling services. Data were analysed using JMP 8.0 software. RESULTS:
      Respondents were 52.4% of 202 eligible students. Mean age was 24.1 +/- 5.0 years.
      Females constituted 54.7%. Muslims were 72.7% while Gambians formed 77.0%.
      Commonest specialties chosen by females were Obstetrics/Gynaecology, Paediatrics
      and Surgery in that order, while males preferred Internal Medicine, Surgery and
      Obstetrics/Gynaecology. Commonest factors influencing choices by females were
      'focus on urgent care' (65.5%) and 'intellectual content of specialty' (56.9%).
      For males, these were 'intellectual content of specialty' (60.4%) and 'focus on
      urgent care' / 'individual's competence' (50.0% each). More females (30.0%) than
      males (23.0%) had ever received career counseling, but all students desired it.
      CONCLUSIONS: Significant gender differences exist in specialty choices and
      factors influencing these choices amongst these students. All want career
      counseling.

PMID- 22873699
TI  - Do traumatic brain contusions increase in size after decompressive craniectomy?
AB  - Hemorrhagic contusions (HC) represent a common consequence of traumatic brain
      injury (TBI) and usually evolve during the first 12 h after trauma. The
      relationship between decompressive craniectomy (DC) and evolution of the post
      traumatic HC is still unclear. The aim of the present study was to evaluate the
      impact of DC on HC evolution. Fifty-seven patients with the evidence of at least
      one HC at admission CT scan were analyzed. Twenty-five patients (Group 1)
      underwent DC and 32 patients underwent medical therapy alone (Group 2). Fisher's
      exact test was used to compare categorical variables. Logistic regression model
      was used to assess the independent contribution of predictive factors (age, <=50
      years; treatment received, DC vs. medical; anticoagulant/antiplatelet drugs
      intake; Rotterdam CT score, 1-3 vs. 4-6) to the evolution/new appearance of an
      HC. A significant increase (>=2 cc) of any HC during the observation period was
      detected in 8 patients (14%): 4/25 patients (16%) of Group 1 and 4/32 patients
      (12.5%) of Group 2 (Fisher exact test two-sided p=0.72). Univariate and
      multivariate analyses showed that none of the analyzed factors was associated
      with increased or de novo appearance of any HC. DC does not seem to constitute a
      risk factor for the evolution of HC.

PMID- 22873700
TI  - Outcomes of a home telehealth intervention for patients with diabetes and
      hypertension.
AB  - BACKGROUND: Home telehealth programs often focus on a single disease, yet many
      patients who need monitoring have multiple conditions. This study evaluated
      secondary outcomes from a clinical trial evaluating the efficacy of home
      telehealth to improve outcomes of patients with co-morbid diabetes and
      hypertension. SUBJECTS AND METHODS: A single-center randomized controlled
      clinical trial compared two remote monitoring intensity levels (low and high) and
      usual care in patients with type 2 diabetes and hypertension being treated in
      primary care. Secondary outcomes assessed were knowledge (diabetes, hypertension,
      medications), self-efficacy, adherence (diabetes, medications), and patient
      perceptions of the intervention mode. RESULTS: Knowledge scores improved in the
      high-intensity intervention group participants, but upon further analysis, we
      found the intervention effect was not mediated by gain in knowledge. No
      significant differences were found across the groups in self-efficacy, adherence,
      or patient perceptions of the intervention mode. CONCLUSIONS: Home telehealth can
      enhance detection of key clinical symptoms that occur between regular physician
      visits. While our intervention improved glycemic and blood pressure control, the
      mechanism of the effect for this improvement was not clear.

PMID- 22873701
TI  - Therapeutic anti-methamphetamine antibody fragment-nanoparticle conjugates:
      synthesis and in vitro characterization.
AB  - Treatments specific to the medical problems caused by methamphetamine (METH)
      abuse are greatly needed. Toward this goal, we are developing new multivalent
      anti-METH antibody fragment-nanoparticle conjugates with customizable
      pharmacokinetic properties. We have designed a novel anti-METH single chain
      antibody fragment with an engineered terminal cysteine (scFv6H4Cys). Generation 3
      (G3) polyamidoamine dendrimer nanoparticles were chosen for conjugation due to
      their monodisperse properties and multiple amine functional groups. ScFv6H4Cys
      was conjugated to G3 dendrimers via a heterobifunctional PEG cross-linker that is
      reactive to a free amine on one end and a thiol group on the other. PEG modified
      dendrimers were synthesized by reacting the PEG cross-linker with dendrimers in a
      stoichiometric ratio of 11:1, which were further reacted with 3-fold molar excess
      of anti-METH scFv6H4Cys. This reaction resulted in a heterogeneous mix of G3-PEG
      scFv6H4Cys conjugates (dendribodies) with three to six scFv6H4Cys conjugated to
      each dendrimer. The dendribodies were separated from the unreacted PEG modified
      dendrimers and scFv6H4Cys using affinity chromatography. A detailed in vitro
      characterization of the PEG modified dendrimers and the dendribodies was
      performed to determine size, purity, and METH binding function. The dendribodies
      were found to have affinity for METH identical to that of the unconjugated
      scFv6H4Cys in saturation binding assays, whereas the PEG modified dendrimers had
      no affinity for METH. These data suggest that an anti-METH scFv can be
      successfully conjugated to a PEG modified dendrimer nanoparticle with no adverse
      effects on METH binding properties. This study is a critical step toward
      preclinical characterization and development of a novel nanomedicine for the
      treatment of METH abuse.

PMID- 22873702
TI  - alpha-Geminal dihydroxymethyl piperidine and pyrrolidine iminosugars: synthesis,
      conformational analysis, glycosidase inhibitory activity, and molecular docking
      studies.
AB  - The Jocic-Reeve and Corey-Link type reaction of dichloromethyllithium with
      suitably protected 5-keto-hexofuranoses followed by treatment with sodium azide
      and sodium borohydride reduction gave 5-azido-5-hydroxylmethyl substituted
      hexofuranoses 7a-c with required geminal dihydroxymethyl group. Removal of
      protecting groups and converting the C-1 anomeric carbon into free hemiacetal
      followed by intramolecular reductive aminocyclization with in situ generated C5
      amino functionality afforded corresponding 5C-dihydroxymethyl piperidine
      iminosugars 2a-c. Alternatively, removal of protecting groups in 7b and 7c and
      chopping of C1-anomeric carbon gave C2-aldehyde that on intramolecular reductive
      aminocyclization with C5-amino gave 4C-dihydroxymethyl pyrrolidine iminosugars 1b
      and 1c, respectively. On the basis of the (1)H NMR studies, the conformations of
      2a/2b were assigned as (4)C(1) and that of 2c as (1)C(4). The glycosidase
      inhibitory activities of all five iminosugars were studied with various
      glycosidase enzymes and compared with natural d-gluco-1-deoxynojirimycin (DNJ).
      All the five compounds were found to be potent inhibitors of rice alpha
      glucosidase with K(i) and IC(50) values in the nanomolar concentration range.
      Iminosugars 2b and 1b were found to be more potent inhibitors than their parent
      iminosugar. These results were substantiated by in silico molecular docking
      studies.

PMID- 22873705
TI  - Choosing to biopsy or refer suspicious melanocytic lesions in general practice.
AB  - BACKGROUND: General practitioners (GPs) are involved in the management of most
      melanocytic skin lesions in Australia. A high quality biopsy technique is a
      crucial first step in management, as it is recognized that poor techniques can
      mislead, delay, or miss a diagnosis of melanoma. There has been little published
      on the biopsy decisions and techniques of GPs. This study aims to describe the
      current management choices made by GPs for suspicious melanocytic skin lesions
      and to compare their choices with the best practice guidelines. METHODS: An
      anonymous survey of GPs presented with three clinical scenarios with increasing
      complexity of melanoma in which a referral or biopsy decision was specified.
      RESULTS: 391 mailed surveys with a 76.3% response rate. Mean biopsy experience
      was 4.14 biopsies per GP per month. The rates of choosing to refer among the
      three scenarios were 31%, 52% and 81% respectively, with referral to surgery
      being the most common choice (81%). Most biopsy techniques (55%) were chosen
      according to best practice guidelines, although non-guideline biopsy techniques
      chosen included shave (n=10), punch biopsy (n=57), wide excisions (n=65), and
      flaps (n=10). The few GPs (n=5) who identified themselves as skin specialist GPs
      were no more likely to adhere to guidelines than their colleagues. CONCLUSION: A
      majority of referrals and biopsies were chosen by GPs according to best practice
      guidelines, but concern remains for the high proportion of GPs making non
      guideline based choices. How GPs choose to biopsy or refer needs further
      training, audit, and research if Australia is to improve the outcome of melanoma
      management in general practice.

PMID- 22873706
TI  - Purification of silicon powder by the formation of thin porous layer followed
      byphoto-thermal annealing.
AB  - Porous silicon has been prepared using a vapor-etching based technique on a
      commercial silicon powder. Strong visible emission was observed in all samples.
      Obtained silicon powder with a thin porous layer at the surface was subjected to
      a photo-thermal annealing at different temperatures under oxygen atmosphere
      followed by a chemical treatment. Inductively coupled plasma atomic emission
      spectrometry results indicate that silicon purity is improved from 99.1% to
      99.994% after annealing at 900 degrees C.

PMID- 22873704
TI  - Prognostic impact of detecting viable circulating tumour cells in gastric cancer
      patients using a telomerase-specific viral agent: a prospective study.
AB  - BACKGROUND: The identification of circulating tumour cells (CTCs) in peripheral
      blood is a useful approach to estimate prognosis, monitor disease progression,
      and measure treatment effects in various malignancies. However, clinical
      relevance of CTCs is controversial. We attempted to detect viable CTCs in the
      peripheral blood of gastric cancer patients using a telomerase-specific viral
      agent. METHODS: We took a 7.5-ml blood sample from 65 treatment-negative gastric
      cancer patients before surgery and 10 healthy volunteers. We detected viable CTCs
      in the blood samples after incubating them with a telomerase-specific,
      replication-selective, oncolytic adenoviral agent carrying the green fluorescent
      protein (GFP) gene (OBP-401). GFP-positive CTCs were defined as having a diameter
      of at least 7.735 MUm; this threshold was determined by receiver operating
      characteristic curve analysis. GFP-positive cells were counted under a
      fluorescence microscope. RESULTS: There was a significant difference in overall
      survival among the patients with 0-4 and those with >=5 GFP-positive CTCs in the
      stage I-IV disease group and stage II-IV advanced disease group. The number of
      GFP-positive CTCs was not related to cancer stage. Among the pathological
      findings, the number of GFP-positive CTCs was only significantly related to
      venous invasion, although there were trends towards more GFP-positive CTCs with
      disease progression (tumour depth, lymph node metastasis, distant metastasis,
      lymphatic invasion, and histological type). CONCLUSIONS: There was a significant
      relationship between the number of GFP-positive CTCs and overall survival in the
      patients with gastric cancer. The detection of CTCs using OBP-401 may be useful
      for prognostic evaluation. TRIAL REGISTRATION: University Hospital Medical
      Information Network in Japan, UMIN000002018.

PMID- 22873707
TI  - Operational efficiency and sustainability of vector control of malaria and
      dengue: descriptive case studies from the Philippines.
AB  - BACKGROUND: Analysis is lacking on the management of vector control systems in
      disease-endemic countries with respect to the efficiency and sustainability of
      operations. METHODS: Three locations were selected, at the scale of province,
      municipality and barangay (i.e. village). Data on disease incidence, programme
      activities, and programme management were collected on-site through meetings and
      focus group discussions. RESULTS: Adaptation of disease control strategies to the
      epidemiological situation per barangay, through micro-stratification, brings
      gains in efficiency, but should be accompanied by further capacity building on
      local situational analysis for better selection and targeting of vector control
      interventions within the barangay. An integrated approach to vector control,
      aiming to improve the rational use of resources, was evident with a multi-disease
      strategy for detection and response, and by the use of combinations of vector
      control methods. Collaboration within the health sector was apparent from the
      involvement of barangay health workers, re-orientation of job descriptions and
      the creation of a disease surveillance unit. The engagement of barangay leaders
      and use of existing community structures helped mobilize local resources and
      voluntary services for vector control. In one location, local authorities and the
      community were involved in the planning, implementation and evaluation of malaria
      control, which triggered local programme ownership. CONCLUSIONS: Strategies that
      contributed to an improved efficiency and sustainability of vector control
      operations were: micro-stratification, integration of vector control within the
      health sector, a multi-disease approach, involvement of local authorities, and
      empowerment of communities. Capacity building on situational analysis and vector
      surveillance should be addressed through national policy and guidelines.

PMID- 22873708
TI  - A reproducible, high throughput method for fabricating fibrin gels.
AB  - BACKGROUND: Fibrin gels are a promising biomaterial for tissue engineering.
      However, current fabrication methods are time intensive with inherent variation.
      There is a pressing need to develop new and consistent approaches for producing
      fibrin-based hydrogels for examination. FINDINGS: We developed a high throughput
      method for creating fibrin gels using molds fabricated from polydimethylsiloxane
      (PDMS). Fibrin gels were produced by adding solutions of fibrinogen and thrombin
      to cylindrical defects in a PDMS sheet. Undisturbed gels were collected by
      removing the sheet, and fibrin gels were characterized. The characteristics of
      resulting gels were compared to published data by measuring compressive stiffness
      and osteogenic response of entrapped human mesenchymal stem cells (MSCs). Gels
      exhibited compressive moduli nearly identical to our previously reported
      fabrication method. Trends in alkaline phosphatase activity, an early marker of
      osteogenic differentiation in MSCs, were also consistent with previous data.
      CONCLUSIONS: These findings demonstrate a streamlined approach to fibrin gel
      production that drastically reduces the time required to make fibrin gels, while
      also reducing variability between gel batches. This fabrication technique
      provides a valuable tool for generating large numbers of gels in a cost-effective
      manner.

PMID- 22873709
TI  - Design, synthesis, and biological evaluation of novel transrepression-selective
      liver X receptor (LXR) ligands with 5,11-dihydro-5-methyl-11-methylene-6H
      dibenz[b,e]azepin-6-one skeleton.
AB  - To obtain novel transrepression-selective liver X receptor (LXR) ligands, we
      adopted a strategy of reducing the transactivational agonistic activity of the
      5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10,
      which exhibits LXR-mediated transrepressional and transactivational activity.
      Structural modification of 10 based on the reported X-ray crystal structure of
      the LXR ligand-binding domain led to a series of compounds, of which almost all
      exhibited transrepressional activity at 1 or 10 MUM but showed no
      transactivational activity even at 30 MUM. Among the compounds obtained, 18 and
      22 were confirmed to have LXR-dependent transrepressional activity by using
      peritoneal macrophages from wild-type and LXR-null mice. A newly developed
      fluorescence polarization assay indicated that they bind directly to LXRalpha.
      Next, further structural modification was performed with the guidance of docking
      simulations with LXRalpha, focusing on enhancing the binding of the ligands with
      LXRalpha through the introduction of substituents or heteroatom(s). Among the
      compounds synthesized, compound 48, bearing a hydroxyl group, showed potent,
      selective, and dose-dependent transrepressional activity.

PMID- 22873710
TI  - Negative consequences of using alpha = 0.05 for environmental monitoring
      decisions: a case study from a decade of Canada's Environmental Effects
      Monitoring Program.
AB  - Using the traditional alpha = 0.05 significance level for null hypothesis
      significance tests makes assumptions about relative costs of Type I vs relevant
      Type II errors and inflates their combined probabilities. We have examined the
      results of 1254 monitoring tests conducted under the Canadian Environmental
      Effects Monitoring (EEM) program from 1992 to 2003, focusing on how the choice of
      alpha affected the relative probabilities and implied costs of Type I and Type II
      errors. Using alpha = 0.05 resulted in implied relative costs of Type I vs Type
      II errors that were both inconsistent among monitoring end points and also
      inconsistent with the philosophy of the monitoring program. Using alpha = 0.05
      also resulted in combinations of Type I and II error that were 15-17% larger than
      those for "optimal" alpha levels set to minimize Type I and II errors for each
      study, and 12% of all monitoring tests would have reached opposite conclusions
      had they used these optimal alpha levels for decision-making. Thus, if the
      Canadian EEM program used study-specific optimal alpha levels, they would reduce
      the incidence of relevant errors and eliminate inconsistent implied relative
      costs of these errors. Environmental research and monitoring programs using alpha
      = 0.05 as a decision-making threshold should re-evaluate the usefulness of this
      "one-size-fits-all" approach.

PMID- 22873711
TI  - Molecular dynamics simulations of iron- and aluminum-loaded serum transferrin:
      protonation of Tyr188 is necessary to prompt metal release.
AB  - Serum transferrin (sTf) carries iron in blood serum and delivers it into cells by
      receptor-mediated endocytosis. The protein can also bind other metals, including
      aluminum. The crystal structures of the metal-free and metal-loaded protein
      indicate that the metal release process involves an opening of the protein. In
      this process, Lys206 and Lys296 lying in the proximity of each other form the
      dilysine pair or, so-called, dilysine trigger. It was suggested that the
      conformational change takes place due to variations of the protonation state of
      the dilysine trigger at the acidic endosomal pH. In 2003, Rinaldo and Field
      (Biophys. J. 85, 3485-3501) proposed that the dilysine trigger alone can not
      explain the opening and that the protonation of Tyr188 is required to prompt the
      conformational change. However, no evidence was supplied to support this
      hypothesis. Here, we present several 60 ns molecular dynamics simulations
      considering various protonation states to investigate the complexes formed by sTf
      with Fe(III) and Al(III). The calculations demonstrate that only in those systems
      where Tyr188 has been protonated does the protein undergo the conformational
      change and that the dilysine trigger alone does not lead to the opening. The
      simulations also indicate that the metal release process is a stepwise mechanism,
      where the hinge-bending motion is followed by the hinge-twisting step. Therefore,
      the study demonstrates for the first time that the protonation of Tyr188 is
      required for the release of metal from the metal loaded sTf and provides valuable
      information about the whole process.

PMID- 22873712
TI  - Bilateral osteoporotic bone marrow defects of the mandible: a case report.
AB  - Osteoporotic bone marrow defect of the jaws has been reported as a poorly
      demarcated radiolucency that affect mainly posterior mandible of middle-aged
      woman. The incidence of this condition is not exactly established and its
      pathogenesis remains unknown. An additional unusual case of osteoporotic bone
      marrow defects occurring bilaterally in the mandibular edentulous regions of a 32
      year-old white woman is presented reinforcing its diagnostic criteria and
      histopathological findings.

PMID- 22873713
TI  - Size-dependent partitioning of nano/microparticles mediated by membrane lateral
      heterogeneity.
AB  - It is important that we understand the physical, chemical, and biological
      mechanisms that govern the interaction between nanoparticles (NPs) and
      heterogeneous cellular surfaces because of the possible cytotoxicity of
      engineered nanomaterials. In this study, we investigated the lateral localization
      of nano/microparticles within a biomimetic heterogeneous membrane interface using
      cell-sized two-phase liposomes. We found that lateral heterogeneity in the
      membrane mediates the partitioning of nano/microparticles in a size-dependent
      manner: small particles with a diameter of <=200 nm were localized in an ordered
      phase, whereas large particles preferred a fluidic disordered phase. This
      partitioning behavior was verified by temperature-controlled membrane miscibility
      transition and laser-trapping of associated particles. In terms of the membrane
      elastic energy, we present a physical model that explains this localization
      preference of nano/microparticles. The calculated threshold diameter of particles
      that separates the particle-partitioning phase was 260 nm, which is in close
      agreement with our observation (200 nm). These findings may lead to a better
      understanding of the basic mechanisms that underlie the association of
      nanomaterials within a cell surface.

PMID- 22873714
TI  - The role of microperc in the treatment of symptomatic lower pole renal calculi.
AB  - BACKGROUND AND PURPOSE: The treatment of symptomatic lower pole (LP) calculi
      poses a challenge because of lower clearance rates. We present our experience
      with microperc in the treatment of LP renal calculi. PATIENTS AND METHODS: We
      retrospectively evaluated the symptomatic patients with LP renal calculi who
      underwent microperc between August 2011 and June 2012 from two referral
      hospitals. Patients were included only in cases of failure after shockwave
      lithotripsy (SWL) or retrograde intrarenal surgery (RIRS) and according to
      patient preference. The percutaneous renal access was performed using the 4.8F
      "all-seeing needle" with C-arm fluoroscopy or ultrasonographic guidance with the
      patient in the prone position. Stone disintegration was established using a 200
      MUm holmium:yttrium-aluminum-garnet laser fiber. RESULTS: A total of 21 patients
      (mean age 37.3 +/- 20.1 years) with LP stone underwent microperc. The mean body
      mass index was 28.6 +/- 6.0 kg/m(2), and the mean stone size was 17.8 +/- 5.9 (9
      29) mm. The duration of surgery and fluoroscopic screening was 62.8 +/- 25.2
      minutes and 150.5 +/- 92.8 seconds, respectively. The patients were discharged
      after a mean 37.5 +/- 14.4 hours of hospitalization time. The mean hemoglobin
      drop was 0.8 +/- 0.6 (0.1-2.3) g/dL. Conversion to miniperc was necessitated in
      one patient with loss of vision. Stone-free status was achieved in 18 (85.7%)
      patients. Clinically insignificant residual fragments were observed in only one
      (4.8%). The procedure failed in two (9.5%) patients. A total of two minor
      complications (renal colic necessitating stent insertion and urinary tract
      infection) were observed postoperatively, none severe. CONCLUSION: Microperc is a
      feasible and efficient treatment modality for symptomatic LP calculi. Our results
      provide that microperc might take a part in case of SWL and RIRS failures or as
      an alternative to percutaneous nephrolithotomy or RIRS in the management of
      symptomatic LP calculi.

PMID- 22873715
TI  - Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced
      oxidative stress and vascular dysfunction in mice.
AB  - Quercetin, a dietary antioxidant flavonoid, possesses strong anti-inflammatory
      and cytoprotective activities. The effects were investigated in an animal model
      of lipopolysaccharide (LPS)-induced endotoxaemia and vascular dysfunction in
      vivo. Male ICR mice were injected with LPS (10 mg/kg; i.p.). Quercetin (50 or 100
      mg/kg) was intragastrically administered either before or after LPS
      administration. Fifteen hours after LPS injection, mice were found in
      endotoxaemic condition, as manifested by hypotension, tachycardia, and blunted
      vascular responses to vasodilators and vasoconstrictor. The symptoms were
      accompanied by increased aortic iNOS protein expression, decreased aortic eNOS
      protein expression, marked suppression of cellular glutathione (GSH) redox
      status, enhanced aortic superoxide production, increased plasma malodialdehyde
      and protein carbonyl, and elevated urinary nitrate/nitrite. Treatment with
      quercetin either before or after LPS preserved the vascular function, as blood
      pressure, heart rate, vascular responsiveness were restored to near normal
      values, particularly when quercetin was given as a preventive regimen. The
      vascular protective effects were associated with upregulation of eNOS expression,
      reduction of oxidative stress, and maintained blood GSH redox ratio. Overall
      findings suggest the beneficial effect of quercetin on the prevention and
      restoration of a failing eNOS system and alleviation of oxidative stress and
      vascular dysfunction against endotoxin-induced shock in mice.

PMID- 22873717
TI  - Developing the evidence-base for Safe Communities: a multi-level, partly
      randomised, controlled trial.
AB  - Safe Communities, representing a global activation of the public health logic,
      may be strengthened through theoretical, methodological and empirical support. In
      the spirit of this Special Issue that aims to analyse the achievements and
      challenges inherent to Safe Communities, we offer our contribution in the form of
      a methodology of a multi-country child safety, peace and health promotion study.
      The study, situated within an African-centred initiative called Ukuphepha - an
      isiZulu word meaning demonstrating African safety - is underpinned by four
      theoretical claims that frame injury and violence prevention as a multi
      disciplinary issue to be addressed through a suite of interventions to family and
      extended social systems. The interventions, sensitive to the priorities of each
      participating country, have been informed by the literature on effective
      interventions and the authors' joint experiences of community development. The
      study is designed as a population-based, multi-level, multi-intervention partly
      randomised controlled trial, and there are potentially 24 participant communities
      representing South Africa, Mozambique, Egypt, Zambia, Uganda, Bangladesh,
      Malaysia and Australia - over three commencement phases. Whereas process
      evaluation will focus on community engagement, impact evaluation will consider
      risk and protective factors, and outcome evaluation will examine the overall
      effectiveness of the interventions. Notwithstanding the many challenges, the
      study will provide insights into the methodology and mechanisms of ecologically
      oriented interventions that locate injury and violence prevention as an activity
      arising from safety, peace and health promotion.

PMID- 22873719
TI  - Training emotional intelligence improves both emotional intelligence and
      depressive symptoms in inpatients with borderline personality disorder and
      depression.
AB  - OBJECTIVE: Borderline personality disorder (BPD) is defined as a pervasive
      pattern of instability in emotion, mood and interpersonal relationships, with a
      comorbidity between PBD and depressive disorders (DD). A key competence for
      successful management of interpersonal relationships is emotional intelligence
      (EI). Given the low EI of patients suffering from BPD, the present study aimed at
      investigating the effect on both emotional intelligence and depression of
      training emotional intelligence in patients with BPD and DD. METHODS: A total of
      30 inpatients with BPD and DD (53% females; mean age 24.20 years) took part in
      the study. Patients were randomly assigned either to the treatment or to the
      control group. Pre- and post-testing 4 weeks later involved experts' rating of
      depressive disorder and self-reported EI. The treatment group received 12
      sessions of training in components of emotional intelligence. RESULTS: Relative
      to the control group, EI increased significantly in the treatment group over
      time. Depressive symptoms decreased significantly over time in both groups,
      though improvement was greater in the treatment than the control group.
      CONCLUSION: For inpatients suffering from BPD and DD, regular skill training in
      EI can be successfully implemented and leads to improvements both in EI and
      depression. Results suggest an additive effect of EI training on both EI and
      depressive symptoms.

PMID- 22873721
TI  - Participant observation at the end-of-life: reflecting on tears.

PMID- 22873722
TI  - Biomarkers in amyotrophic lateral sclerosis: is there a neurovascular pathway?
AB  - The establishment of a link between VEGF, hypoxia and ALS pathogenesis placed
      angiogenic factors and oxidative stress at the focal point for further studies.
      Recreation of a phenotype strikingly similar to that of mutant SOD1 mouse and
      human ALS, like muscle weakness and atrophy owing to lower motor neuron
      degeneration was observed following the targeted deletion of the hypoxia response
      element (HRE) from promoter of mouse vascular endothelial growth factor (VEGF).
      The crucial link between vasculature, angiogenic molecules and motor neuron
      degeneration has thus been constantly scrutinized. In this review, we have
      proposed to correlate human, in vitro and cadaveric studies so as to find out
      whether molecules like VEGF and various others, at the interface of neurovascular
      network and oxidative stress, have a prognostic, diagnostic and therapeutic
      potential for treatment of a fatal neurodegenerative disorder namely ALS.

PMID- 22873723
TI  - Oxidative stress in post-acute ischemic stroke patients after intensive
      neurorehabilitation.
AB  - We investigated in post-acute ischemic stroke patients the influence of intensive
      neurorehabilitation on oxidative stress balance during recovery of neurological
      deficits. For this purpose, fourteen patients were included in the study within
      30 days of stroke onset. Outcome measures were the National Institutes of Health
      Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index, and the
      Katz Index. Redox balance was assessed by measuring plasma peroxidative by
      products, nitrite/nitrate metabolites (NOx), as an index of nitric oxide (NO),
      Cu/Zn Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration,
      autoantibodies against ox-LDL (OLAB) serum level and plasma antioxidant capacity.
      Assessments were made before and after neurorehabilitation. Fifteen apparently
      healthy controls were investigated to compare redox markers. Intensive
      neurorehabilitation was associated with an improvement of all the outcome
      measures (P < 0.05). Decreased values of peroxidative by-products and of NOx (P <
      0.05) were observed after neurorehabilitation in stroke patients even though
      their values were higher than in controls (P < 0.05). Changes observed before and
      after neurorehabilitation in NIHSS scores (Delta NIHSS scores) and in plasma NOx
      amount (Delta NOx) correlated positively (r=0.79; P < 0.005). No differences in
      EC-SOD activity, OLAB and serum urate concentrations were found between stroke
      patients and controls, before and after neurorehabilitation. Total plasma
      antioxidant capacity, lower in stroke patients than in controls before
      neurorehabilitation, was unchanged thereafter. Our data provide evidence of the
      effectiveness of neurorehabilitation on reducing redox unbalance in stroke
      patients and hints the role of NO as a messenger involved in post-ischemic
      neuronal plasticity influencing recovery of neurological deficits.

PMID- 22873725
TI  - Doxorubicin-induced in vivo nephrotoxicity involves oxidative stress-mediated
      multiple pro- and anti-apoptotic signaling pathways.
AB  - Doxorubicin (DOX), a prominent anticancer agent has enjoyed considerable
      popularity in the last few decades because of its usefulness in the management of
      various forms of cancers, but its organotoxic potential (cardio-, hepatoand
      nephrotoxicity) has constrained on its clinical use. This study investigated
      whether DOX has the ability to cause nephrotoxicity in vivo and if so, whether it
      is linked to oxidative stress (OS). Another important goal was to describe
      whether expression of pro- and anti-apoptotic genes in kidneys was driven by OS.
      In order to explore DOX's nephrotoxic potential, male rats (Sprague Dawley; 500
      520g; fed ad libitum) were administered i.p. with a single dose of DOX (12 mg/kg)
      on day one and sacrificed seven days later (day 8). Changes in serum chemistries
      (i.e., serum urea nitrogen, SUN, and creatinine) were determined immediately upon
      sacrifice, whereas kidney tissues were subjected to several sensitive biomarkers
      for OS, such as, lipid peroxidation, Superoxide dismutase (SOD) activity and
      chromatin fragmentation. The most important goal was to evaluate the select
      expression of Apaf-1, Caspase-3, Bad, Bax, Bcl-2, Bcl-xL, p53 and Mdm2 genes in
      order to understand the underlying link between extrinsic and intrinsic pathways
      of cell death. Data revealed that DOX-exposed animals showed significant
      nephrotoxicity as reflected in increased SUN (5.6-fold) and creatinine (2.65
      fold) levels with considerably decreased body weight. Increases in kidney injury
      markers reflected parallel elevations in lipid peroxidation (1.7-fold) and
      genomic DNA fragmentation (2.9 fold) coupled with a proportionate reduction in
      total SOD activity suggesting DOX-assaulted kidneys encountered massive OS.
      Western blot showed very striking changes: i) substantial increases in the
      expression of pro-apoptotic APAF-1, Caspase-3, Bax and Bad proteins; ii)
      Reduction in the expression of anti-apoptotic Bcl-2 and Bcl-xL genes; iii)
      considerable increase in the expression of p53 and suppression of its regulator
      Mdm2. Serum chemistry and tissue biochemistry mirrored histopathology. In
      conclusion, this study for the first time may have shown a close link between
      mitochondrial perturbations and cell death regulating genes during DOXinduced
      nephrotoxicity, and described DOX's potential to inflict kidney injury in
      addition to other organs during chemotherapy in clinical setting.

PMID- 22873726
TI  - Delayed cerebral ischemia after subarachnoid hemorrhage: from vascular spasm to
      cortical spreading depolarizations.
AB  - Non-traumatic subarachnoid hemorrhage (SAH) represents about 5 to 6% of the
      overall incidence of stroke and is associated with high morbidity and mortality.
      Despite the substantial research and clinical efforts, delayed cerebral ischemia
      (DCI) is still the major complication after SAH and represents an important
      factor for severe neurological deficits. Cerebral vasospasm (VSP) has been
      recognised for a long time as an important underlying pathophysiologic cause of
      DCI, but it is now clearer that the mechanisms underlying DCI are multifactorial.
      Among other pathomechanisms proposed, ischemia-producing cortical spreading
      depolarizations (CSDs) are likely to be involved in DCI development.
      Understanding the plethora of different pathophysiological derangements after SAH
      is very important for the development of new therapies, in order to abolish
      secondary ischemic brain injuries early-on and improve patients' outcome. In this
      review, we strive to summarise the mechanisms and therapeutic developments of
      DCI.

PMID- 22873724
TI  - Wnt1 inducible signaling pathway protein 1 (WISP1) targets PRAS40 to govern beta
      amyloid apoptotic injury of microglia.
AB  - Given the present challenges to attain effective treatment for beta-amyloid
      (Abeta) toxicity in neurodegenerative disorders such as Alzheimer's disease,
      development of novel cytoprotective pathways that can assist immune mediated
      therapies through the preservation of central nervous system microglia could
      offer significant promise. We show that the CCN4 protein, Wnt1 inducible
      signaling pathway protein 1 (WISP1), is initially up-regulated by Abeta and can
      modulate its endogenous expression for the protection of microglia during Abeta
      mediated apoptosis. WISP1 activates mTOR and phosphorylates p70S6K and 4EBP1
      through the control of the regulatory mTOR component PRAS40. Loss of PRAS40
      through gene reduction or inhibition by WISP1 is cytoprotective. WISP1 ultimately
      governs PRAS40 by sequestering PRAS40 intracellularly through post-translational
      phosphorylation and binding to protein 14-3-3. Our work identifies WISP1, mTOR
      signaling, and PRAS40 as targets for new strategies directed against Alzheimer's
      disease and related disorders.

PMID- 22873727
TI  - Deletion of endoplasmic reticulum stress-induced CHOP protects microvasculature
      post-spinal cord injury.
AB  - Trauma introduces damaging stressors that compromise protein, lipid, and nucleic
      acid integrity. Aggregates of unfolded and misfolded proteins in the endoplasmic
      reticulum (ER) triggers the ER stress response (ERSR)/unfolded protein response
      (UPR) leading to activation of three signaling pathways mediated by PERK, ATF6,
      and IRE1. Initially, the ERSR/UPR is pro-homeostatic as it globally slows
      translation while increasing translation of chaperone proteins and inducing ER
      associated degradation. If the cellular stress is not controlled, apoptosis is
      subsequently induced through several mechanisms, of which the most well-described
      is CHOP. Following spinal cord injury (SCI), mice deficient in CHOP signaling
      show increased spared white matter and enhanced locomotor recovery by 6 weeks. At
      24 hours after SCI, ATF4 and CHOP are upregulated in under perfused microvessels.
      We observed vascular protection 3 days post-SCI and a significant decrease in
      macrophage infiltration by the end of the first week. These results suggest that
      modulating ER-stress signaling in endothelial cells and macrophages may protect
      against vascular injury and attenuate inflammation post-SCI.

PMID- 22873728
TI  - Human umbilical cord mesenchymal stem cell therapy on neuromyelitis optica.
AB  - Stem cell transplantation is a promising therapy for neuromyelitis optica (NMO).
      Among stem cell varieties, human umbilical cord-derived mesenchymal stem cells
      (hUC-MSCs) possess many advantages, add a differential potential into neural
      cells, secrete a set of trophic factors and cytokines, regulate immunological
      function, and have therapeutic potential for neurological diseases. In this
      study, hUC-MSCs transplantation was used to treat five NMO patients with follow
      up for 18 months including evaluation of Expanded Disability Status Scale (EDSS)
      levels, clinical course, magnetic resonance imaging (MRI) characteristics,
      adverse events, and so on. Among the five cases, four showed therapeutic
      improvement after hUC-MSCs treatment. Both symptoms and signs improved and
      relapse frequencies were reduced. MRI characteristics also showed decreased
      volume and severity of lesions, while few adverse events occurred. The results
      suggest that hUC-MSCs transplantation appear safe and might be effective for NMO
      treatment in the near future. In addition, according to flow cytometry assay
      (FACS) results, B cells of blood were inhibited while T cells increased after
      treatment, indicating an immune-related mechanism.

PMID- 22873729
TI  - Early classification of multivariate temporal observations by extraction of
      interpretable shapelets.
AB  - BACKGROUND: Early classification of time series is beneficial for biomedical
      informatics problems such including, but not limited to, disease change
      detection. Early classification can be of tremendous help by identifying the
      onset of a disease before it has time to fully take hold. In addition, extracting
      patterns from the original time series helps domain experts to gain insights into
      the classification results. This problem has been studied recently using time
      series segments called shapelets. In this paper, we present a method, which we
      call Multivariate Shapelets Detection (MSD), that allows for early and patient
      specific classification of multivariate time series. The method extracts time
      series patterns, called multivariate shapelets, from all dimensions of the time
      series that distinctly manifest the target class locally. The time series were
      classified by searching for the earliest closest patterns. RESULTS: The proposed
      early classification method for multivariate time series has been evaluated on
      eight gene expression datasets from viral infection and drug response studies in
      humans. In our experiments, the MSD method outperformed the baseline methods,
      achieving highly accurate classification by using as little as 40%-64% of the
      time series. The obtained results provide evidence that using conventional
      classification methods on short time series is not as accurate as using the
      proposed methods specialized for early classification. CONCLUSION: For the early
      classification task, we proposed a method called Multivariate Shapelets Detection
      (MSD), which extracts patterns from all dimensions of the time series. We showed
      that the MSD method can classify the time series early by using as little as 40%
      64% of the time series' length.

PMID- 22873730
TI  - Brazilian version of the Jefferson Scale of Empathy: psychometric properties and
      factor analysis.
AB  - BACKGROUND: Empathy is a central characteristic of medical professionalism and
      has recently gained attention in medical education research. The Jefferson Scale
      of Empathy is the most commonly used measure of empathy worldwide, and to date it
      has been translated in 39 languages. This study aimed to adapt the Jefferson
      Scale of Empathy to the Brazilian culture and to test its reliability and
      validity among Brazilian medical students. METHODS: The Portuguese version of the
      Jefferson Scale of Empathy was adapted to Brazil using back-translation
      techniques. This version was pretested among 39 fifth-year medical students in
      September 2010. During the final fifth- and sixth-year Objective Structured
      Clinical Examination (October 2011), 319 students were invited to respond to the
      scale anonymously. Cronbach's alpha, exploratory factor analysis, item-total
      correlation, and gender comparisons were performed to check the reliability and
      validity of the scale. RESULTS: The student response rate was 93.7% (299
      students). Cronbach's coefficient for the scale was 0.84. A principal component
      analysis confirmed the construct validity of the scale for three main factors:
      Compassionate Care (first factor), Ability to Stand in the Patient's Shoes
      (second factor), and Perspective Taking (third factor). Gender comparisons did
      not reveal differences in the scores between female and male students.
      CONCLUSIONS: The adapted Brazilian version of the Jefferson Scale of Empathy
      proved to be a valid, reliable instrument for use in national and cross-cultural
      studies in medical education.

PMID- 22873731
TI  - Health-related behaviors in women with lifestyle-related diseases.
AB  - Lifestyle related diseases associated with physical inactivity and poor diet
      quality, represent a major health burden. This study assessed negative and
      positive health habits and health care utilization in healthy women (n = 50) and
      women with lifestyle related diseases such as polycystic ovary syndrome (PCOS) (n
      = 50), gestational diabetes mellitus (GDM) (n = 44) and type 2 diabetes (DM2) (n
      = 43). A significant difference existed across groups for negative health habits
      (P = .012) with a trend for positive health habits (P = .06) elevated in women
      with PCOS. Women with DM2 had the highest amount of health care utilization
      including doctors office visits (P < .001), overnight hospital treatments (P <
      .001) and emergency room treatments (P = .01). Health practitioners would benefit
      from both encouraging positive health habits and addressing negative health
      habits. Furthermore, self-management and emphasizing the pivotal role patients'
      have in managing their illness is important for optimizing health outcomes.
      Elevated health care utilization rates were observed in women with DM2 but there
      were no differences in positive health habits across sub-groups. Encouraging
      lifestyle modification in women with precursor diseases such as GDM and PCOS is
      vital in order to prevent progression to DM2.

PMID- 22873732
TI  - The role of body image and depression in tanning behaviors and attitudes.
AB  - In the current study, we examined correlates of tanning behaviors and attitudes.
      Undergraduates (N = 277; 53% female; average age = 19.27 years) completed
      measures of appearance orientation and appearance evaluation from the
      Multidimensional Body-Self Relations Questionnaire, the Center for
      Epidemiological Studies Depression Scale, and questions addressing tanning
      behaviors and attitudes. Women were more likely to engage in indoor tanning and
      perceived greater susceptibility to photoaging than men. Body image and
      depression were associated with tanning behaviors and attitudes. Results suggest
      that psychological factors are important motivators of both indoor and outdoor
      tanning, although each has unique correlates. Implications for reducing risky
      tanning behaviors are discussed.

PMID- 22873733
TI  - Self-control is associated with physical activity and fitness among young males.
AB  - The personality trait self-control has been associated with various adaptive
      outcomes. The objective of this cross-sectional study was to explore whether self
      control is associated with self-reported leisure time physical activity (LTPA),
      Body Mass Index (BMI), muscle-fitness and aerobic fitness among young men.
      Participants (482 male conscripts; age M = 20) completed a questionnaire and
      participated in anthropometric measurements in the DefenceNutri Study, and took
      standard aerobic fitness and muscle fitness tests as part of their military
      training. Self-control was found to have a positive association with LTPA,
      aerobic fitness, and muscle fitness, and a negative association with BMI. Self
      control predicted aerobic and muscular fitness regardless of BMI, and remained a
      significant and independent predictor of aerobic fitness (R2 (adj.) = .28, beta =
      .10, p < .05), but not muscle fitness, when LTPA and BMI were controlled for.

PMID- 22873734
TI  - Mediators of change in psychosocial interventions for cancer patients: a
      systematic review.
AB  - Careful reviews and meta-analyses have made valuable contributions to
      understanding the efficacy of psychosocial interventions for cancer patients. An
      important next step is to determine the mediators that explain the influence of
      efficacious interventions on outcomes. This systematic review summarizes tests of
      mediating variables from twenty-two projects conducted from 1989-2010. Although
      all authors provided some type of rationale for considering particular mediating
      relationships, the investigations varied widely with respect to the extent to
      which formal theoretical constructs were tested, the type and goals of the
      interventions studied, and the broad types of outcomes and potential mediators
      examined. Although there was some evidence supporting selected mediating
      relationships, with positive findings often found when mediating variables
      represented behaviors targeted by an intervention, the findings were mixed.
      Expanding the focus of research to include mechanisms in psychosocial oncology
      intervention research is necessary for providing a unified picture of how
      mediating relationships may be operating in this field.

PMID- 22873735
TI  - PEGylation of proteins in organic solution: a case study for interferon beta-1b.
AB  - Conventional protein PEGylation is carried out in aqueous solution. However, some
      hydrophobic proteins seem to be stable in organic solution. In this study, a
      novel approach of PEGylating IFN-beta-1b in an organic solution of 2-butanol (2
      BuOH) was investigated. Compared with protein PEGylation in aqueous solution, the
      overall modification yields increased more than 37%, while the yield of mono
      PEGylated products could be increased by 36%. Furthermore, the PEGylated IFN-beta
      1b, which was obtained in organic solution, demonstrated 18% more antiviral
      potency than those derived from aqueous solution. The PEGylation step could be
      directly connected to the previous protein separation step for process
      integration. Dynamic light scattering (DLS) and atomic force microscope (AFM)
      analysis revealed that IFN-beta-1b formed aggregates both in water and in 2-BuOH
      solutions. However, the aggregates were much smaller and more homogeneous in 2
      BuOH than those in aqueous solution, thereby providing larger solvent accessible
      protein surfaces, which resulted in a more productive PEGylation process. In
      addition, the results of circular dichroism (CD), fluorescence spectra, and
      peptide mapping suggested that the increased bioactivity came from the difference
      in PEGylation site distribution due to solution environment that induced
      conformational discrepancy. The results of this study show that PEGylation of IFN
      beta-1b in organic solution is a facile and efficient process, which might find
      applications for other hydrophobic proteins.

PMID- 22873736
TI  - Computation of isotopic peak center-mass distribution by Fourier transform.
AB  - We derive a new efficient algorithm for the computation of the isotopic peak
      center-mass distribution of a molecule. With the use of Fourier transform
      techniques, the algorithm accurately computes the total abundance and average
      mass of all the isotopic species with the same number of nucleons. We evaluate
      the performance of the method with 10 benchmark proteins and other molecules;
      results are compared with BRAIN, a recently reported polynomial method. The new
      algorithm is comparable to BRAIN in accuracy and superior in terms of speed and
      memory, particularly for large molecules. An implementation of the algorithm is
      available for download.

PMID- 22873737
TI  - Preoperative factors influencing success in pterygium surgery.
AB  - BACKGROUND: To identify preoperative, perioperative and postoperative risk
      factors that influence the success of pterygium surgery. METHODS: This is a
      prospective study of thirty-six patients with primary or recurrent pterygia. A
      detailed anamnesis and an ophthalmological examination were performed looking for
      the following factors: age, race, latitude and altitude of the main place of
      residence, hours of exposure to the sun, use of protective measures against UV
      radiation, classification of pterygium, width of the pterygium at limbus,
      surgical technique (conjunctival autograft plus suturing versus tissue glue),
      graft alterations (misapposition, granuloma, haemorrhage, oedema, retraction or
      necrosis), and postoperative symptoms (foreign-body sensation, pain). The
      examinations were performed 2 and 7 days and 2, 6 and 12 months after surgery. In
      addition, recurrence was defined as any growth of conjunctiva into the cornea.
      RESULTS: A logistic regression and a survival analysis have been used to perform
      data analysis. A total number of 36 patients completed a one year follow-up. A
      total of 13 patients were born and lived in Spain, and 26 came from other
      countries, mostly Latin America. A total number of 8 males (no women) presented a
      recurrence, mainly between 2 and 6 months. The hours of sun exposure through
      their life was independently related to surgical success. Pterygia of less than 5
      mm of base width showed a weak positive correlation with recurrence. None of the
      other factors considered were significantly related to recurrence. CONCLUSIONS:
      Male gender and high sun exposure are strongly and independently related to
      surgical success after the removal of pterygia.

PMID- 22873738
TI  - Angle-dependent carrier transmission in graphene p-n junctions.
AB  - Angle-dependent carrier transmission probability in graphene p-n junctions is
      investigated. Using electrostatic doping from buried gates, p-n junctions are
      formed along graphene channels that are patterned to form different angles with
      the junction. A peak in the junction resistance is observed, which becomes
      pronounced with angle. This angular dependence is observed for junctions made on
      both exfoliated and CVD-grown graphene and is consistent with the theoretically
      predicted dependence of transmission probability on incidence angle.

PMID- 22873741
TI  - Role of treatment in the appearance and selection of BCR-ABL1 kinase domain
      mutations.
AB  - BACKGROUND AND OBJECTIVE: The availability of different tyrosine kinase
      inhibitors (TKIs) with distinct anti-leukemic potency enables optimization of
      current therapeutic regimens; however, some patients lose their therapy response
      and acquire TKI resistance. In this study, we describe a single-center experience
      of monitoring BCR-ABL1 kinase domain (KD) mutations and discuss the impact of
      treatment on mutation selection. METHODS: Chronic myelogenous leukemia (CML)
      patients treated with TKIs at the Department of Internal Medicine-Hematology and
      Oncology, Masaryk University and University Hospital Brno during 2003-2011 were
      included in this study. A total number of 100 patients who did not achieve an
      optimal therapy response or who lost their therapy response were screened for the
      presence of BCR-ABL1 KD mutations, using direct sequencing. RESULTS: Our data
      show that pretreatment with non-specific non-TKI drugs prior to TKI therapy does
      not preferentially select for initial BCR-ABL1 KD mutations, in contrast to first
      line imatinib therapy, which shows a clear predominance of T315I or P-loop
      mutations compared with mutations located in other KD regions. In addition, the
      median time to detection of P-loop mutations was substantially shorter in
      patients treated with first-line imatinib than in those pretreated with non-TKI
      drugs. Furthermore, analysis of CML patients who had recurrent resistance to TKI
      therapy revealed possible therapy-driven selection of BCR-ABL1 KD mutations.
      Finally, we confirm the previously described poor prognosis of CML patients with
      mutations in the BCR-ABL1 KD, since 40.0% of our CML patients who harbored a BCR
      ABL1 KD mutation died from CML while receiving TKI treatment. Moreover, among the
      patients who are still on treatment, 27.8% have already progressed. Our data also
      confirm the unique position of the T315I mutation with respect to its strong
      resistance to currently approved TKIs. CONCLUSION: On the basis of the 'real
      life' data described in this study, it is possible that the therapy itself
      results in its failure and selects the most resistant mutations under the
      selective pressure of the applied therapy regimen in some CML patients who harbor
      BCR-ABL1 KD mutations.

PMID- 22873739
TI  - Molecular characterization of head and neck cancer: how close to personalized
      targeted therapy?
AB  - Molecular targeted therapy in head and neck squamous cell carcinoma (HNSCC)
      continues to make strides, and holds much promise. Cetuximab remains the sole US
      FDA-approved molecular targeted therapy available for HNSCC, though several new
      biologic agents targeting the epidermal growth factor receptor (EGFR) and other
      pathways are currently in the regulatory approval pipeline. While targeted
      therapies have the potential to be personalized, their current use in HNSCC is
      not personalized. This is illustrated for EGFR-targeted drugs, where EGFR as a
      molecular target has yet to be individualized for HNSCC. Future research needs to
      identify factors that correlate with response (or lack of one) and the underlying
      genotype-phenotype relationship that dictates this response. Comprehensive
      exploration of genetic and epigenetic landscapes in HNSCC is opening new
      frontiers to further enlighten and mechanistically inform newer as well as
      existing molecular targets, and to set a course for eventually translating these
      discoveries into therapies for patients. This opinion offers a snapshot of the
      evolution of molecular subtyping in HNSCC and its current clinical applicability,
      as well as new emergent paradigms with implications for controlling this disease
      in the future.

PMID- 22873743
TI  - Radiostrontium in the western North Pacific: characteristics, behavior, and the
      Fukushima impact.
AB  - The impact of the Fukushima-derived radiostrontium ((90)Sr and (89)Sr) on the
      western North Pacific Ocean has not been well established, although (90)Sr
      concentrations recorded in surface seawater offshore of the damaged Fukushima Dai
      ichi nuclear power plant were in some areas comparable to or even higher than (as
      those in December 2011 with 400 kBq m(-3)(90)Sr) the (137)Cs levels. The total
      amount of (90)Sr released to the marine environment in the form of highly
      radioactive wastewater could reach about 1 PBq. Long-term series (1960-2010) of
      (90)Sr concentration measurements in subtropical surface waters of the western
      North Pacific indicated that its concentration has been decreasing gradually with
      a half-life of 14 y. The pre-Fukushima (90)Sr levels in surface waters, including
      coastal waters near Fukushima, were estimated to be 1 Bq m(-3). To better assess
      the impact of about 4-5 orders of magnitude increased radiostrontium levels on
      the marine environment, more detail measurements in seawater and biota of the
      western North Pacific are required.

PMID- 22873740
TI  - Individualized therapy for gastroesophageal reflux disease: potential impact of
      pharmacogenetic testing based on CYP2C19.
AB  - The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton
      pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend
      on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of
      CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1),
      intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where
      *1 and X represent the wild type and the mutant allele, respectively. RMs include
      ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics
      and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups.
      Plasma PPI levels and intragastric pH values during PPI treatment are lowest in
      the RM group, intermediate in the IM group, and highest in the PM group. These
      CYP2C19-genotype-dependent differences in the pharmacokinetics and
      pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI
      treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for
      GERD. CYP2C19 pharmacogenetics should be taken into consideration for the
      personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19
      genotype testing in GERD therapy should be verified in clinical studies.

PMID- 22873744
TI  - IGRT versus non-IGRT for postoperative head-and-neck IMRT patients: dosimetric
      consequences arising from a PTV margin reduction.
AB  - BACKGROUND: To evaluate the impact of image-guided radiation therapy (IGRT)
      versus non-image-guided radiation therapy (non-IGRT) on the dose to the clinical
      target volume (CTV) and the cervical spinal cord during fractionated intensity
      modulated radiation therapy (IMRT) for head-and-neck cancer (HNC) patients.
      MATERIAL AND METHODS: For detailed investigation, 4 exemplary patients with daily
      control-CT scans (total 118 CT scans) were analyzed. For the IGRT approach a
      target point correction (TPC) derived from a rigid registration focused to the
      high-dose region was used. In the non-IGRT setting, instead of a TPC, an
      additional cohort-based safety margin was applied. The dose distributions of the
      CTV and spinal cord were calculated on each control-CT and the resulting dose
      volume histograms (DVHs) were compared with the planned ones fraction by
      fraction. The D50 and D98 values for the CTV and the D5 values of the spinal cord
      were additionally reported. RESULTS: In general, the D50 and D98 histograms show
      no remarkable difference between both strategies. Yet, our detailed analysis also
      reveals differences in individual dose coverage worth inspection. Using IGRT, the
      D5 histograms show that the spinal cord less frequently receives a higher dose
      than planned compared to the non-IGRT setting. This effect is even more
      pronounced when looking at the curve progressions of the respective DVHs.
      CONCLUSIONS: Both approaches are equally effective in maintaining CTV coverage.
      However, IGRT is beneficial in spinal cord sparing. The use of an additional
      margin in the non-IGRT approach frequently results in a higher dose to the spinal
      cord than originally planned. This implies that a margin reduction combined with
      an IGRT correction helps to maintain spinal cord dose sparing best as possible.
      Yet, a detailed analysis of the dosimetric consequences dependent on the used
      strategy is required, to detect single fractions with unacceptable dosimetric
      deviations.

PMID- 22873746
TI  - A hospital-based estimate of major causes of death among under-five children from
      a health facility in Lagos, Southwest Nigeria: possible indicators of health
      inequality.
AB  - INTRODUCTION: Current evidence on the root-causes of deaths among children
      younger than 5 years is critical to direct international efforts to improve child
      survival, focus on health promotion and achieve Millennium Development Goal 4. We
      report a hospital-based estimate for 2005-2007 of the major causes of death in
      children in this age-group in south-west Nigeria. METHODS: We used retrospective
      data from the intensive care unit of a second-tier health facility to extract the
      presenting complaints, clinical diagnosis, treatment courses, prognosis and
      outcome among children aged 6-59 months. SPSS-19 was used for data analysis.
      RESULTS: Of the 301 children (58% males, 42% females) admitted into the ICU
      within the period of study, 173 (26%) presented with complaints related to the
      gastrointestinal system, 138 (21%) with respiratory symptoms and 196 (29%) with
      complaints of fever. Overall, 708 investigations were requested for among which
      were full blood count (215, 30%) and blood slides for malaria parasite (166,
      23%). Infection ranked highest (181, 31%) in clinicians' diagnosis, followed by
      haematological health problems (109, 19%) and respiratory illnesses (101, 17%).
      There were negative correlations between outcome of the illness and patient's
      weight (r=-0.195, p=0.001) and a strong positive correlation between prognosis
      and outcome of admission (r=0.196, p=0.001). Of the 59 (20%) children that died,
      presentation of respiratory tract illnesses were significantly higher in females
      (75%) than in males (39%) (chi2=7.06; p=0.008) and diagnoses related to
      gastrointestinal pathology were significantly higher in males (18%) than in
      females (0%) (chi2=4.07; p=0.05). Majority of the deaths (21%) occurred among
      children aged 1.0 to 1.9 years old and among weight group of 5.1-15.0 kg.
      CONCLUSION: The major causes of deaths among under-five years old originate from
      respiratory, gastrointestinal and infectious diseases - diseases that were
      recognized as major causes of childhood mortality about half a century earlier.
      Realization of MDG4 - to reduce child mortality by two-thirds - is only possible
      if the government and donor agencies look beyond the health sector to find hidden
      causative factors such as education and housing and within the health sector such
      as vibrant maternal, new-born, and child health interventions.

PMID- 22873745
TI  - Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting
      mesenchymal stem cell and osteoprogenitor frequency.
AB  - Parathyroid hormone (PTH) anabolic osteoporosis therapy is intrinsically limited
      by unknown mechanisms. We previously showed that disabling the transcription
      factor Nmp4/CIZ in mice expanded this anabolic window while modestly elevating
      bone resorption. This enhanced bone formation requires a lag period to
      materialize. Wild-type (WT) and Nmp4-knockout (KO) mice exhibited equivalent PTH
      induced increases in bone at 2 weeks of treatment, but by 7 weeks, the null mice
      showed more new bone. At 3-week treatment, serum osteocalcin, a bone formation
      marker, peaked in WT mice, but continued to increase in null mice. To determine
      if 3 weeks is the time when the addition of new bone diverges and to investigate
      its cellular basis, we treated 10-week-old null and WT animals with human PTH (1
      34) (30 MUg/kg/day) or vehicle before analyzing femoral trabecular architecture
      and bone marrow (BM) and peripheral blood phenotypic cell profiles. PTH-treated
      Nmp4-KO mice gained over 2-fold more femoral trabecular bone than WT by 3 weeks.
      There was no difference between genotypes in BM cellularity or profiles of
      several blood elements. However, the KO mice exhibited a significant elevation in
      CFU-F cells, CFU-F(Alk)(Phos+) cells (osteoprogenitors), and a higher percentage
      of CFU-F(Alk)(Phos+) cells/CFU-F cells consistent with an increase in CD45
      /CD146+/CD105+/nestin+ mesenchymal stem cell frequency. Null BM exhibited a 2
      fold enhancement in CD8+ T cells known to support osteoprogenitor differentiation
      and a 1.6-fold increase in CFU-GM colonies (osteoclast progenitors). We propose
      that Nmp4/CIZ limits the PTH anabolic window by restricting the number of BM
      stem, progenitor, and blood cells that support anabolic bone remodeling.

PMID- 22873747
TI  - Non-innocent dissociation of H2O on GaP(110): implications for electrochemical
      reduction of CO2.
AB  - The structural and electronic properties of the GaP(110)/H(2)O interface have
      been investigated by first-principles density functional theory calculations. Our
      results suggest that hydride-like H atoms are present on the surface as a
      consequence of the dissociation of water in contact with the GaP surface. This
      feature opens up a new feasible reduction pathway for CO(2) where the GaP(110)
      surface is the electrochemically active entity.

PMID- 22873748
TI  - Variable blocking temperature of a porous silicon/Fe3O4 composite due to
      different interactions of the magnetic nanoparticles.
AB  - In the frame of this work, the aim was to create a superparamagnetic
      nanocomposite system with a maximized magnetic moment when magnetized by an
      external field and a blocking temperature far below room temperature. For this
      purpose, iron oxide nanoparticles of 3.8-, 5- and 8-nm size have been infiltrated
      into the pores of porous silicon. To fabricate tailored magnetic properties of
      the system, the particle size and the magnetic interactions among the particles
      play a crucial role. Different concentrations of the particles dispersed in
      hexane have been used for the infiltration to vary the blocking temperature TB,
      which indicates the transition between the superparamagnetic behavior and blocked
      state. TB is not only dependent on the particle size but also on the magnetic
      interactions between them, which can be varied by the particle-particle distance.
      Thus, a modification of the pore loading on the one hand and of the porous
      silicon morphology on the other hand results in a composite material with a
      desired blocking temperature. Because both materials, the mesoporous silicon
      matrices as well as the Fe3O4 nanoparticles, offer low toxicity, the system is a
      promising candidate for biomedical applications.

PMID- 22873749
TI  - Identification of potential opinion leaders in child health promotion in Sweden
      using network analysis.
AB  - BACKGROUND: Opinion leaders are often local individuals with high credibility who
      can influence other people. Robust effects using opinion leaders in diffusing
      innovations have been shown in several randomized controlled trials, for example
      regarding sexually transmitted infections (STI), human immunodeficiency virus
      (HIV) prevention, mammography rates and caesarean birth delivery rates. In a
      Cochrane review 2010 it was concluded that the use of opinion leaders can
      successfully promote evidence-based practice. Thus, using opinion leaders within
      the public health sector might be one means to speed up the dissemination of
      health promoting and disease preventing innovations. Social network analysis has
      been used to trace and map networks, with focus on relationships and positions,
      in widely spread arenas and topics. The purpose of this study was to use social
      network analysis in order to identify potential opinion leaders at the arena of
      child health promotion in Sweden. RESULTS: By using snowball technique a short e
      mail question was spread in up to five links, starting from seven initially
      invited persons. This inquiry resulted in a network consisting of 153
      individuals. The most often mentioned actors were researchers, public health
      officials and paediatricians, or a combination of these professions. Four single
      individuals were mentioned by five to seven other persons in the network. These
      individuals obviously possess qualities that make other professionals within the
      public health sector listen to and trust them. CONCLUSIONS: Social network
      analysis seemed to be a useful method to identify influential persons with high
      credibility, i.e. potential opinion leaders, at the arena of child health
      promotion in Sweden. If genuine opinion leaders could be identified directed
      measures can be carried out in order to spread new and relevant knowledge. This
      may facilitate for public health actors at the local, regional and national level
      to more rapidly progress innovations into everyday practice. However,
      effectiveness studies of opinion leaders in the public health sector still have
      to be performed.

PMID- 22873750
TI  - Editorial: keeping track of an expanding subject--recent trends in immunology and
      their clinical implications.

PMID- 22873751
TI  - Modulation of environmental reduplicative paramnesia by perceptual experience.
AB  - Environmental reduplicative paramnesia (ERP) is characterized by the involuntary
      attribution of a false identity to a place. ERP has rarely been examined
      experimentally; its mechanisms therefore remain speculative. Here, we describe a
      patient with extended traumatic right fronto-temporal damage and severe
      persistent ERP, in whom we were able to modulate ERP by exposing him to various
      typical landmarks of the town where he was hospitalized. When landmarks were
      ambiguous as regards location (e.g., unknown buildings), the patient erroneously
      localized himself in his hometown, which was more than two thousand kilometers
      away. In contrast, when he visited distinct landmarks of the place where he
      actually resided, his ERP was immediately corrected, and spatial orientation was
      restored. These findings indicate that ERP may be temporarily modifiable through
      perception of unequivocal topographic information. 

PMID- 22873752
TI  - Comparing apples and pears: women's perceptions of their body size and shape.
AB  - BACKGROUND: Obesity is a growing public health problem among reproductive-aged
      women, with consequences for chronic disease risk and reproductive and obstetric
      morbidities. Evidence also suggests that body shape (i.e., regional fat
      distribution) may be independently associated with risk, yet it is not known if
      women adequately perceive their shape. This study aimed to assess the validity of
      self-reported body size and shape figure drawings when compared to anthropometric
      measures among reproductive-aged women. METHODS: Self-reported body size was
      ascertained using the Stunkard nine-level figures and self-reported body shape
      using stylized pear, hourglass, rectangle, and apple figures. Anthropometry was
      performed by trained researchers. Body size and body mass index (BMI) were
      compared using Spearman's correlation coefficient. Fat distribution indicators
      were compared across body shapes for nonobese and obese women using analysis of
      variance (ANOVA) and Fisher's exact test. Percent agreement and kappa statistics
      were computed for apple and pear body shapes. RESULTS: The 131 women studied were
      primarily Caucasian (81%), aged 32 years, with a mean BMI of 27.1 kg/m(2) (range
      16.6-52.8 kg/m(2)). The correlation between body size and BMI was 0.85 (p<0.001).
      Among nonobese women, waist-to-hip ratios (WHR) were 0.75, 0.75, 0.80, and 0.82
      for pear, hourglass, rectangle, and apple, respectively (p<0.001). Comparing
      apples and pears, the percent agreement (kappa) for WHR>=0.80 was 83% (0.55).
      CONCLUSIONS: Self-reported size and shape were consistent with anthropometric
      measures commonly used to assess obesity and fat distribution, respectively. Self
      reported body shape may be a useful proxy measure in addition to body size in
      large-scale surveys.

PMID- 22873753
TI  - Implementation of a lifestyle intervention for type 2 diabetes prevention in
      Dutch primary care: opportunities for intervention delivery.
AB  - BACKGROUND: As in clinical practice resources may be limited compared to
      experimental settings, translation of evidence-based lifestyle interventions into
      daily life settings is challenging. In this study we therefore evaluated the
      implementation of the APHRODITE lifestyle intervention for the prevention of type
      2 diabetes in Dutch primary care. Based on this evaluation we discuss
      opportunities for refining intervention delivery. METHODS: A 2.5-year
      intervention was performed in 14 general practices in the Netherlands among
      individuals at high risk for type 2 diabetes (FINDRISC-score >= 13) (n = 479) and
      was compared to usual care (n = 446). Intervention consisted of individual
      lifestyle counselling by nurse practitioners (n = 24) and GPs (n = 48) and group
      consultations. Drop-out and attendance were registered during the programme.
      After the intervention, satisfaction with the programme and perceived
      implementation barriers were assessed with questionnaires. RESULTS: Drop-out was
      modest (intervention: 14.6 %; usual care: 13.2 %) and attendance at individual
      consultations was high (intervention: 80-97 %; usual care: 86-94 %). Providers
      were confident about diabetes prevention by lifestyle intervention in primary
      care. Participants were more satisfied with counselling from nurse practitioners
      than from GPs. A major part of the GPs reported low self-efficacy regarding
      dietary guidance. Lack of counselling time (60 %), participant motivation (12 %),
      and financial reimbursement (11 %) were regarded by providers as important
      barriers for intervention implementation. CONCLUSIONS: High participant
      compliance and a positive attitude of providers make primary care a suitable
      setting for diabetes prevention by lifestyle counselling. Results support a role
      for the nurse practitioner as the key player in guiding lifestyle modification.
      Further research is needed on strategies that could increase cost-effectiveness,
      such as more stringent criteria for participant inclusion, group-counselling,
      more tailor-made counselling and integration of screening and / or interventions
      for different disorders.

PMID- 22873754
TI  - Onychopharmacokinetics of terbinafine hydrochloride penetration from a novel
      topical formulation into the human nail in vitro.
AB  - This study determined the onychopharmacokinetics, nail absorption, distribution,
      and penetration of [14C]-terbinafine HCl in a new topical formulation
      into/through the human finger nail using the in vitro finite dose model. This
      study determined the penetration rate of terbinafine HCl from multiple doses of
      topical formulation applied daily for 14 days. Results showed that the total dose
      recovery (mass balance) was almost 100%. The concentration of terbinafine HCl in
      the deeper nail plate (ventral/intermediate layers) and the cotton-pad nail bed
      samples after the 14-day treatment were 613 +/- 145 and (+/-S.D.) and 27 +/- 1.2
      ug/cm3 (or 1.9 +/- 0.6 ug/cm3 daily) on average, respectively. In comparison with
      nail concentration data from the literature for other topical terbinatine
      formulations, our results show that higher amounts of terbinafine HCl reached the
      deep nail plate and/or the nail bed after a 14-day topical treatment with this
      topical formulation in vitro.

PMID- 22873755
TI  - Fraction SX of maitake mushroom favorably influences blood glucose levels and
      blood pressure in streptozotocin-induced diabetic rats.
AB  - We assessed whether fraction SX derived from maitake mushroom could play a
      beneficial role in the treatment of a laboratory model of type-1 diabetes by
      decreasing circulating glucose levels and lowering blood pressure (BP). We
      injected 50 mg/kg body weight (BW) streptozotocin (STZ) intraperitoneally (i.p.)
      into 48 male Sprague-Dawley rats (SD) to produce a laboratory model of type-1
      diabetes. SD were divided into four groups of 12 SD. A control group ate straight
      pulverized rat chow. To three treatment groups, we added into the pulverized rat
      chow: gliclazide (10 mg/kg), pioglitazone (10-30 mg/kg), or maitake SX (2.5
      g/kg). In addition to measuring BW, circulating glucose level, and BP, the
      following procedures were also carried out: insulin challenge (insulin
      sensitivity), losartan challenge (renin-angiotensin system activity), Nw-nitro-L
      arginine-methyl ester hydrochloride (LNAME) challenge (nitric oxide [NO] system
      activity), and evaluation of serum angiotensin converting enzyme (ACE) activity.
      All treatments compared with control generally decreased circulating glucose
      levels, but only the maitake SX consistently enhanced measured insulin
      sensitivity. We found that maitake SX could significantly lower systolic blood
      pressure (SBP) in diabetic SD. In general, only SD receiving maitake SX, not the
      two drugs, showed decreased activity of the renin-angiotensin system and
      increased NO system activity compared with control under the conditions examined.
      Our results suggest that maitake SX may be useful for treating perturbations in
      glucose-insulin metabolism and elevated BP in type-1 diabetes.

PMID- 22873756
TI  - The catalytic mechanism of the hotdog-fold enzyme superfamily 4-hydroxybenzoyl
      CoA thioesterase from Arthrobacter sp. strain SU.
AB  - The hotdog-fold enzyme 4-hydroxybenzoyl-coenzyme A (4-HB-CoA) thioesterase from
      Arthrobacter sp. strain AU catalyzes the hydrolysis of 4-HB-CoA to form 4
      hydroxybenzoate (4-HB) and coenzyme A (CoA) in the final step of the 4
      chlorobenzoate dehalogenation pathway. Guided by the published X-ray structures
      of the liganded enzyme (Thoden, J. B., Zhuang, Z., Dunaway-Mariano, D., and
      Holden H. M. (2003) J. Biol. Chem. 278, 43709-43716), a series of site-directed
      mutants were prepared for testing the roles of active site residues in substrate
      binding and catalysis. The mutant thioesterases were subjected to X-ray structure
      determination to confirm retention of the native fold, and in some cases, to
      reveal changes in the active site configuration. In parallel, the wild-type and
      mutant thioesterases were subjected to transient and steady-state kinetic
      analysis, and to (18)O-solvent labeling experiments. Evidence is provided that
      suggests that Glu73 functions in nucleophilic catalysis, that Gly65 and Gln58
      contribute to transition-state stabilization via hydrogen bond formation with the
      thioester moiety and that Thr77 orients the water nucleophile for attack at the 4
      hydroxybenzoyl carbon of the enzyme-anhydride intermediate. The replacement of
      Glu73 with Asp was shown to switch the function of the carboxylate residue from
      nucleophilic catalysis to base catalysis and thus, the reaction from a two-step
      process involving a covalent enzyme intermediate to a single-step hydrolysis
      reaction. The E73D/T77A double mutant regained most of the catalytic efficiency
      lost in the E73D single mutant. The results from (31)P NMR experiments indicate
      that the substrate nucleotide unit is bound to the enzyme surface. Kinetic
      analysis of site-directed mutants was carried out to determine the contributions
      made by Arg102, Arg150, Ser120, and Thr121 in binding the nucleotide unit.
      Lastly, we show by kinetic and X-ray analyses of Asp31, His64, and Glu78 site
      directed mutants that these three active site residues are important for
      productive binding of the substrate 4-hydroxybenzoyl ring.

PMID- 22873757
TI  - Abstracts of the 11th Annual UT-ORNL-KBRIN Bioinformatics Summit 2012.
      Louisville, Kentucky, USA. March 30-April 1, 2012.

PMID- 22873759
TI  - The c-Met inhibitors: a new class of drugs in the battle against advanced
      nonsmall-cell lung cancer.
AB  - Lung cancer, of which non-small-cell lung cancer (NSCLC) is the most common form,
      remains the leading cause of cancer-related mortality worldwide, with many
      patients presenting with advanced disease at initial diagnosis. In advanced NSCLC
      patients whose tumors harbor activating epidermal growth factor receptor (EGFR)
      mutations, the use of EGFR tyrosine kinase inhibitors (TKIs) as first-line
      treatment has provided an unusually large progression-free-survival (PFS)
      benefit, a significantly high response rate (RR) and decreased toxicity when
      compared with cytotoxic chemotherapy in several phase III randomized trials;
      however, resistance invariably occurs. There are multiple mechanisms defined by
      which tumor cells may become independent of EGFR such as the well-characterized
      example of mesenchymal-epithelial transition factor (MET) amplification. Upon
      initial diagnosis of NSCLC, MET gene amplification is uncommon; however, acquired
      MET amplification has been noted in up to 20% of EGFR-mutated tumors that have
      been pretreated with an EGFR TKI. In tumors containing MET gene amplification,
      stimulation of the tumor occurs via the co-receptor HER-3 resulting in activation
      of the phosphatidylinositol-3-kinase (PI3K) signaling pathway, thereby
      circumventing the effects of an EGFR TKI. Recently, the targeting of the MET
      pathway has been attempted with small molecules and with monoclonal antibodies.
      This review will explain the MET signaling pathway and biology in cancer and the
      recent clinical development and advances of MET/HGF targeting agents in the
      treatment of advanced NSCLC.

PMID- 22873758
TI  - Evaluation of the effects of botulinum toxin A injections when used to improve
      ease of care and comfort in children with cerebral palsy whom are non-ambulant: a
      double blind randomized controlled trial.
AB  - BACKGROUND: Children with cerebral palsy (CP) whom are non-ambulant are at risk
      of reduced quality of life and poor health status. Severe spasticity leads to
      discomfort and pain. Carer burden for families is significant. This study aims to
      determine whether intramuscular injections of botulinum toxin A (BoNT-A) combined
      with a regime of standard therapy has a positive effect on care and comfort for
      children with CP whom are non-ambulant (GMFCS IV/V), compared with standard
      therapy alone (cycle I), and whether repeated injections with the same regime of
      adjunctive therapy results in greater benefits compared with a single injecting
      episode (cycle II). The regime of therapy will include serial casting, splinting
      and/or provision of orthoses, as indicated, combined with four sessions of goal
      directed occupational therapy or physiotherapy. METHOD/DESIGN: This study is a
      double blind randomized controlled trial. Forty participants will be recruited.
      In cycle I, participants will be randomized to either a treatment group who will
      receive BoNT-A injections into selected upper and/or lower limb muscles, or a
      control group who will undergo sham injections. Both groups will receive
      occupational therapy and /or physiotherapy following injections. Groups will be
      assessed at baseline then compared at 4 and 16 weeks following injections or sham
      control. Parents, treating clinicians and assessors will be masked to group
      allocation. In cycle II, all participants will undergo intramuscular BoNT-A
      injections to selected upper and/or lower limb muscles, followed by therapy.The
      primary outcome measure will be change in parent ratings in identified areas of
      concern for their child's care and comfort, using the Canadian Occupational
      Performance Measure (COPM). Secondary measures will include the Care and Comfort
      Hypertonicity Scale (ease of care), the Cerebral Palsy Quality of Life
      Questionnaire (CP QoL-Child) (quality of life), the Caregiver Priorities and
      Child Health Index of Life with Disabilities Questionnaire (CPCHILD(c)) (health
      status) and the Paediatric Pain Profile (PPP) (pain). Adverse events will be
      carefully monitored by a clinician masked to group allocation. DISCUSSION: This
      paper outlines the theoretical basis, study hypotheses and outcome measures for a
      trial of BoNT-A injections and therapy for children with non-ambulant CP. TRIAL
      REGISTRATION: Australia New Zealand Clinical Trials Registry:N12609000360213.

PMID- 22873760
TI  - Lacosamide  in patients with pharmacoresistant epilepsy.
AB  - INTRODUCTION: Lacosamide is a novel antiepileptic drug licensed in the US and
      Europe as adjunctive therapy for partial-onset seizures in adults. The efficacy,
      safety, tolerability and favorable pharmacokinetic profile in the adult
      population suggest that lacosamide could be of benefit for patients with partial
      onset seizures. AREAS COVERED: This paper reviews the available evidence and most
      recent data concerning the efficacy, safety, tolerability and pharmacokinetics of
      lacosamide in adults, as well as in the pediatric population. EXPERT OPINION:
      Lacosamide is one of the newest drugs of the antiepileptic armamentarium, and it
      is expected to compete directly with compounds that are currently used for
      adjunctive therapy in adults with refractory partial epilepsy. The intravenous
      formulation may be used for replacement therapy in patients temporarily unable to
      take oral medication. An apparent lack of sedative or cognitive effects might
      render this drug preferable in patients with mental insufficiency and/or
      epileptic encephalopathy.

PMID- 22873761
TI  - Ethical aspects in tissue research: thematic analysis of ethical statements to
      the research ethics committee.
AB  - BACKGROUND: Many studies have been published about ethics committees and the
      clarifications requested about the submitted applications. In Finland, ethics
      committees require a separate statement on ethical aspects of the research in
      applications to the ethics committee. However, little is known about how
      researchers consider the ethical aspects of their own studies. METHODS: The data
      were collected from all the applications received by the official regional ethics
      committee in the Hospital District of Northern Savo during 2004-2009 (n = 688).
      These included a total of 56 studies involving research on tissue other than
      blood. The statements by the researchers about the ethics about their own
      research in these applications were analyzed by thematic content analysis under
      the following themes: recruitment, informed consent, risks and benefits,
      confidentiality and societal meaning. RESULTS: The researchers tended to describe
      recruitment and informed consent process very briefly. Usually these descriptions
      simply stated who the recruiter was and that written consent would be required.
      There was little information provided on the recruitment situation and on how the
      study recruiters would be informed. Although most of the studies were clinical,
      the possibility was hardly ever discussed that patients could fail to distinguish
      between care and research. CONCLUSION: The written guidelines, available on the
      webpages of the ethics committee, do not seem to be enough to help researchers
      achieve this goal. In addition to detailed guidelines for researchers,
      investigators need to be taught to appreciate the ethical aspects in their own
      studies.

PMID- 22873762
TI  - Reductive detriflylation of N-triflylamides with Red-Al.
AB  - Reduction of cis-N-triflylaziridines with 10 equiv of Red-Al in toluene at -40 to
      0  degrees C selectively afforded corresponding deprotected parent aziridines in
      good to high yields. N,N-Dialkyltriflylamides were also successfully cleaved
      under similar reaction conditions.

PMID- 22873763
TI  - Communicating stigma: the pro-ana paradox.
AB  - This study explores the personal experience of pro-ana bloggers, members of an
      online community for people with eating disorders. Using Erving Goffman's work on
      stigma, this study explores the motivations, benefits, and drawbacks of blogging
      about a stigmatized mental illness, as taken from the bloggers' own perceptive.
      We conducted 33 interviews with bloggers from seven different countries via
      phone, Skype, and e-mail. Participants were motivated to blog because they found
      social support, a way to cope with a stigmatized illness, and means of self
      expression. Participants described blogging as a cathartic experience and
      perceived the social support they received from other members of the pro-ana
      community as a benefit. The fear that the eating disorder will be revealed if the
      blog is exposed and the concern that the blog encourages disordered eating were
      the perceived negative consequences of maintaining such a blog. Thus, blogging
      about anorexia serves to both alleviate and trigger anxiety about living with
      this stigmatized illness. Recommendations for future research are made.

PMID- 22873764
TI  - Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal
      stem cells-mediated cardiac repair.
AB  - Mesenchymal stem cells (MSC) are effective in treating myocardial infarction (MI)
      and previous reports demonstrated that hypoxia improves MSC self-renewal and
      therapeutics. Considering that hypoxia-inducible factor-1 alpha (HIF-1alpha) is a
      master regulator of the adaptative response to hypoxia, we hypothesized that HIF
      1alpha overexpression in MSC could mimic some of the mechanisms triggered by
      hypoxia and increase their therapeutic potential without hypoxia stimulation.
      Transduction of MSC with HIF-1alpha lentivirus vectors (MSC-HIF) resulted in
      increased cell adhesion and migration, and activation of target genes coding for
      paracrine factors. When MSC-HIF were intramyocardially injected in infarcted nude
      rats, significant improvement was found (after treatment of infarcted rats with
      MSC-HIF) in terms of cardiac function, angiogenesis, cardiomyocyte proliferation,
      and reduction of fibrotic tissue with no induction of cardiac hypertrophy. This
      finding provides evidences for a crucial role of HIF-1alpha on MSC biology and
      suggests the stabilization of HIF-1alpha as a novel strategy for cellular
      therapies.

PMID- 22873766
TI  - Cation symmetry effect on the volatility of ionic liquids.
AB  - This work reports the first data for the vapor pressures at several temperatures
      of the ionic liquids, [C(N/2)C(N/2)im][NTf(2)] (N = 4, 6, 8, 10, 12) measured
      using a Knudsen effusion apparatus combined with a quartz crystal microbalance.
      The morphology and the thermodynamic parameters of vaporization derived from the
      vapor pressures, are compared with those for the 1-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide series, [C(N-1)C(1)im][NTf(2)] (N = 3 - 9, 11,
      and 13). It was found that the volatility of [C(N/2)C(N/2)im][NTf(2)] series is
      significantly higher than the asymmetric cation ILs with the same total number of
      carbons in the alkyl side chains, [C(N-1)C(1)im][NTf(2)]. The observed higher
      volatility is related with the lower enthalpy of vaporization. The symmetric
      cation, [C(N/2)C(N/2)im][NTf(2)], presents lower entropies of vaporization
      compared with the asymmetric [C(N-1)C(1)im][NTf(2)], indicating an increase of
      the absolute liquid entropy in the symmetric cation ILs, being a reflection of a
      change of the ion dynamics in the IL liquid phase. Moreover both the enthalpy and
      entropy of vaporization of the [C(N/2)C(N/2)im][NTf(2)] ILs, present a clear odd
      even effect with higher enthalpies/entropies of vaporization for the odd number
      of carbons in each alkyl chain ([C(3)C(3)im][NTf(2)] and [C(5)C(5)im][NTf(2)]).

PMID- 22873765
TI  - Ultrasonic bioreactor as a platform for studying cellular response.
AB  - The need for tissue-engineered constructs as replacement tissue continues to grow
      as the average age of the world's population increases. However, additional
      research is required before the efficient production of laboratory-created tissue
      can be realized. The multitude of parameters that affect cell growth and
      proliferation is particularly daunting considering that optimized conditions are
      likely to change as a function of growth. Thus, a generalized research platform
      is needed in order for quantitative studies to be conducted. In this article, an
      ultrasonic bioreactor is described for use in studying the response of cells to
      ultrasonic stimulation. The work is focused on chondrocytes with a long-term view
      of generating tissue-engineered articular cartilage. Aspects of ultrasound (US)
      that would negatively affect cells, including temperature and cavitation, are
      shown to be insignificant for the US protocols used and which cover a wide range
      of frequencies and pressure amplitudes. The bioreactor is shown to have a
      positive influence on several factors, including cell proliferation, viability,
      and gene expression of select chondrocytic markers. Most importantly, we show
      that a total of 138 unique proteins are differentially expressed on exposure to
      ultrasonic stimulation, using mass-spectroscopy coupled proteomic analyses. We
      anticipate that this work will serve as the basis for additional research which
      will elucidate many of the mechanisms associated with cell response to ultrasonic
      stimulation.

PMID- 22873767
TI  - Early prediction of pathological response in locally advanced rectal cancer based
      on sequential 18F-FDG PET.
AB  - BACKGROUND: The objectives of this study were to investigate the predictive value
      of sequential (18)F-FDG PET scans for pathological tumor response grade (TRG)
      after preoperative chemoradiotherapy (PCRT) in locally advanced rectal cancer
      (LARC) and the impact of partial volume effects correction (PVC). METHODS: Twenty
      eight LARC patients were included. Responders and non-responders status were
      determined in histopathology. PET indices [SUV max and mean, volume and total
      lesion glycolysis (TLG)] at baseline and their evolution after one and two weeks
      of PCRT were extracted by delineation of the PET images, with or without PVC.
      Their predictive value was investigated using Mann-Whitney-U tests and ROC
      analysis. RESULTS: Within baseline parameters, only SUVmean was correlated with
      response. No evolution after one week was predictive of the response, whereas
      after two weeks all the parameters except volume were, the best prediction being
      obtained with TLG (AUC 0.79, sensitivity 63%, specificity 92%). PVC had no
      significant impact on these results. CONCLUSION: Several PET indices at baseline
      and their evolution after two weeks of PCRT are good predictors of response in
      LARC, with or without PVC, whereas results after one week are suboptimal. Best
      predictor was TLG reduction after two weeks, although baseline SUVmean had
      smaller but similar predictive power.

PMID- 22873768
TI  - Cellular interactions on hierarchical poly(epsilon-caprolactone) nanowire
      micropatterns.
AB  - A double template method to fabricate poly(epsilon-caprolactone) (PCL)
      hierarchical patterned nanowires with highly ordered nano- and microscaled
      topography was developed in this study. The topography of PCL film with a
      patterned nanowire surface can be easily and well controlled by changing the
      template and melting time of PCL film on the templates. The surface morphology,
      water contact angle, protein adsorption, and cell growth behavior on the PCL
      films with different surface structures were well studied. The results revealed
      that the PCL nanowire arrays and the hierarchical patterned nanowires showed
      higher capability of protein adsorption and better cell growth than the PCL film
      with smooth surface. Typically, the PCL surface with hierarchical nanowire
      patterns was most favorable for cell attachment and proliferation. The present
      study was innovative at fabrication of polymer substrates with hierarchical
      architecture of nanowires inside microscaled islands to gain insight into the
      cell response to this unique topography and to develop a new method of
      constructing the bionic surface for tissue engineering applications.

PMID- 22873769
TI  - "Makes you proud to be black eh?": reflections on meaningful indigenous research
      participation.
AB  - INTRODUCTION: This article outlines the meaningful participation of eight
      Aboriginal and Torres Strait Islander community members employed as community
      researchers investigating the impact of pandemic influenza in rural and remote
      Indigenous communities in Australia. Aboriginal and Torres Strait Islander
      participation is now a requirement of health research involving Aboriginal and
      Torres Strait Islander communities. There is a growing literature on the
      different approaches to such involvement. Fundamental to this literature is an
      acknowledgement that Indigenous communities are no longer prepared to be research
      objects for external, mostly non-Indigenous researchers, and demand a role in
      decisions about what is researched and how it will be researched. In this paper,
      we describe the protracted process for site identification and recruitment and
      training of community researchers. We focus on the backgrounds of the Indigenous
      researchers and their motivations for involvement, and the strengths and
      challenges posed by Indigenous people researching in their own communities.
      Throughout the paper our concern is to document how genuine participation and the
      building of research capacity can occur. DISCUSSION: A key feature of the
      research was the employment, training and strengthening the capacity of local
      Aboriginal and Torres Strait Islander community members in the role of community
      researchers. A series of training workshops were conducted in northern Australia
      and focussed on qualitative research methods, including data collection, data
      analysis and writing. The Indigenous researchers collected the community-based
      data, and worked in partnership with experienced academic researchers in the
      analysis and compilation of community reports. Parts of those community reports,
      as well as additional information supplied by the community researchers, forms
      the basis of this article. As the demand increases for involvement of Indigenous
      community members as researchers, focus needs to be paid to what constitutes
      meaningful participation. If active participation in all aspects of the research
      process is intended, this necessitates close attention to the knowledge and
      skills required for this to occur at every stage. Building research capacity
      means not simply equipping local people to undertake research on a particular
      project, but to have the knowledge and skills to undertake research in other
      areas. CONCLUSIONS: There are considerable benefits for Indigenous people
      researching in their own communities. Most important for the community
      researchers on this project was the sense that they were doing important health
      work, not just conducting research. Given the persistent gaps between Indigenous
      and non-Indigenous health, this is perhaps one of the most important
      contributions of this type of research. Whilst research outcomes are undoubtedly
      important, in many cases the process used is of greater importance.

PMID- 22873770
TI  - Entangled nanoparticles: discovery by visualization in 4D electron microscopy.
AB  - Particle interactions are fundamental to our understanding of nanomaterials and
      biological assemblies. Here, we report on the visualization of entangled
      particles, separated by as large as 70 nm, and the discovery of channels in their
      near-fields. For silver nanoparticles, the induced field of each particle extends
      to 50-100 nm, but when particles are brought close in separation we observe
      channels as narrow as 6 nm, a width that is 2 orders of magnitude smaller than
      the incident field wavelength. The channels' directions can be controlled by the
      polarization of the incident field, particle size, and separation. For this
      direct visualization of these nanoscopic near-fields, the high spatial, temporal,
      and energy resolutions needed were hitherto not possible without the methodology
      given here. This methodology, we anticipate, paves the way for further
      fundamental studies of particle entanglement and for possible applications
      spanning materials and macromolecular assemblies.

PMID- 22873771
TI  - Target volume definition in high-risk prostate cancer patients using sentinel
      node SPECT/CT and 18 F-choline PET/CT.
AB  - BACKGROUND: To assess the influence of sentinel lymph nodes (SNs) SPECT/CT and 18
      F-choline (18 F-FCH) PET/CT in radiotherapy (RT) treatment planning for prostate
      cancer patients with a high-risk for lymph node (LN) involvement. METHODS: Twenty
      high-risk prostate cancer patients underwent a pelvic SPECT acquisition following
      a transrectal ultrasound guided injection of 99mTc-Nanocoll into the prostate. In
      all patients but one an 18 F-FCH PET/CT for RT treatment planning was performed.
      SPECT studies were coregistered with the respective abdominal CTs. Pelvic SNs
      localized on SPECT/CT and LN metastases detected by 18 F-FCH PET/CT were compared
      to standard pelvic clinical target volumes (CTV). RESULTS: A total of 104 pelvic
      SNs were identified on SPECT/CT (mean 5.2 SNs/patient; range 1-10). Twenty-seven
      SNs were located outside the standard pelvic CTV, 17 in the proximal common iliac
      and retroperitoneal regions above S1, 9 in the pararectal fat and 1 in the
      inguinal region. SPECT/CT succeeded to optimize the definition of the CTV and
      treatment plans in 6/20 patients due to the presence of pararectal SNs located
      outside the standard treatment volume. 18 F-FCH PET/CT identified abnormal tracer
      uptake in the iliac LN region in 2/19 patients. These abnormal LNs were negative
      on SPECT/CT suggesting a potential blockade of lymphatic drainage by metastatic
      LNs with a high tumour burden. CONCLUSIONS: Multimodality imaging which combines
      SPECT/CT prostate lymphoscintigraphy and 18 F-FCH PET/CT identified SNs outside
      standard pelvic CTVs or highly suspicious pelvic LNs in 40% of high-risk prostate
      cancer patients, highlighting the potential impact of this approach in RT
      treatment planning.

PMID- 22873772
TI  - Contributors to suicidality in rural communities: beyond the effects of
      depression.
AB  - BACKGROUND: Rural populations experience a higher suicide rate than urban areas
      despite their comparable prevalence of depression. This suggests the
      identification of additional contributors is necessary to improve our
      understanding of suicide risk in rural regions. Investigating the independent
      contribution of depression, and the impact of co-existing psychiatric disorders,
      to suicidal ideation and suicide attempts in a rural community sample may provide
      clarification of the role of depression in rural suicidality. METHODS: 618
      participants in the Australian Rural Mental Health Study completed the Composite
      International Diagnostic Interview, providing assessment of lifetime suicidal
      ideation and attempts, affective disorders, anxiety disorders and substance-use
      disorders. Logistic regression analyses explored the independent contribution of
      depression and additional diagnoses to suicidality. A receiver operating
      characteristic (ROC) analysis was performed to illustrate the benefit of
      assessing secondary psychiatric diagnoses when determining suicide risk. RESULTS:
      Diagnostic criteria for lifetime depressive disorder were met by 28% (174) of the
      sample; 25% (154) had a history of suicidal ideation. Overall, 41% (63) of
      participants with lifetime suicidal ideation and 34% (16) of participants with a
      lifetime suicide attempt had no history of depression. When lifetime depression
      was controlled for, suicidal ideation was predicted by younger age, being
      currently unmarried, and lifetime anxiety or post-traumatic stress disorder. In
      addition to depression, suicide attempts were predicted by lifetime anxiety and
      drug use disorders, as well as younger age; being currently married and employed
      were significant protective factors. The presence of comorbid depression and PTSD
      significantly increased the odds of reporting a suicide attempt above either of
      these conditions independently. CONCLUSIONS: While depression contributes
      significantly to suicidal ideation, and is a key risk factor for suicide
      attempts, other clinical and demographic factors played an important role in this
      rural sample. Consideration of the contribution of factors such as substance use
      and anxiety disorders to suicidal ideation and behaviours may improve our ability
      to identify individuals at risk of suicide. Acknowledging the contribution of
      these factors to rural suicide may also result in more effective approaches for
      the identification and treatment of at-risk individuals.

PMID- 22873773
TI  - Detection of human coronavirus strain HKU1 in a 2  years old girl with asthma
      exacerbation caused by acute pharyngitis.
AB  - Respiratory viral infections can trigger asthma attack which may lead to sever
      morbidity. In this report, using molecular methods, we show the chronological
      association between human coronavirus--HKU1 infection and asthma exacerbation in
      a two years and seven months old asthmatic girl who was not under treatment and
      was otherwise healthy.

PMID- 22873774
TI  - Copy number variations of the ATP-binding cassette transporter ABCC6 gene and its
      pseudogenes.
AB  - BACKGROUND: The ATP-binding cassette transporter ABCC6 gene is located on
      chromosome 16 between its two pseudogenes (ABCC6P1 and ABCC6P2). Previously, we
      have shown that ABCC6P1 is transcribed and affects ABCC6 at the transcriptional
      level. In this study we aimed to determine copy number variations of ABCC6,
      ABCC6P1 and ABCC6P2 in different populations. Moreover, we sought to study the
      transcription pattern of ABCC6 and ABCC6 pseudogenes in 39 different human
      tissues. FINDINGS: Genomic DNA from healthy individuals from five populations,
      Chinese (n = 24), Middle East (n = 20), Mexicans (n = 24), Caucasians (n = 50)
      and Africans (n = 24), were examined for copy number variations of ABCC6 and its
      pseudogenes by pyrosequencing and quantitative PCR. Copy number variation of
      ABCC6 was very rare (2/142; 1.4%). However, one or three copies of ABCC6P1 were
      relatively common (3% and 8%, respectively). Only one person had a single copy of
      ABCC6P2 while none had three copies. In Chinese, deletions or duplications of
      ABCC6P1 were more frequent than in any other population (9/24; 37.5%). The
      transcription pattern of ABCC6P2 was highly similar to ABCC6 and ABCC6P1, with
      highest transcription in liver and kidney. Interestingly, the total transcription
      level of pseudogenes, ABCC6P1 + ABCC6P2, was higher than ABCC6 in most tissues,
      including liver and kidney. CONCLUSIONS: Copy number variations of the ABCC6
      pseudogenes are quite common, especially in populations of Chinese ancestry. The
      expression pattern of ABCC6P2 in 39 human tissues was highly similar to that of
      ABCC6 and ABCC6P1 suggesting similar regulatory mechanisms for ABCC6 and its
      pseudogenes.

PMID- 22873775
TI  - Influence of cholesterol on the phase transition of lipid bilayers: a temperature
      controlled force spectroscopy study.
AB  - Cholesterol (Chol) plays the essential function of regulating the physical
      properties of the cell membrane by controlling the lipid organization and phase
      behavior and, thus, managing the membrane fluidity and its mechanical strength.
      Here, we explore the model system DPPC:Chol by means of temperature-controlled
      atomic force microscopy (AFM) imaging and AFM-based force spectroscopy (AFM-FS)
      to assess the influence of Chol on the membrane ordering and stability. We
      analyze the system in a representative range of compositions up to 50 mol % Chol
      studying the phase evolution upon temperature increase (from room temperature to
      temperatures high above the T(m) of the DPPC bilayer) and the corresponding
      (nano)mechanical stability. By this means, we correlate the mechanical behavior
      and composition with the lateral order of each phase present in the bilayers. We
      prove that low Chol contents lead to a phase-segregated system, whereas high
      contents of Chol can give a homogeneous bilayer. In both cases, Chol enhances the
      mechanical stability of the membrane, and an extraordinarily stable system is
      observed for equimolar fractions (50 mol % Chol). In addition, even when no
      thermal transition is detected by the traditional bulk analysis techniques for
      liposomes with high Chol content (40 and 50 mol %), we demonstrate that
      temperature-controlled AFM-FS is capable of identifying a thermal transition for
      the supported lipid bilayers. Finally, our results validate the AFM-FS technique
      as an ideal platform to differentiate phase coexistence and transitions in lipid
      bilayers and bridge the gap between the results obtained by traditional methods
      for bulk analysis, the theoretical predictions, and the behavior of these systems
      at the nanoscale.

PMID- 22873776
TI  - Retraction. Terminal gold-oxo complexes.

PMID- 22873777
TI  - Retraction. A palladium-oxo complex. Stabilization of this proposed catalytic
      intermediate by an encapsulating polytungstate ligand.

PMID- 22873778
TI  - DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM): a guide to its use in infants.
AB  - Infanrix hexaTM, a diphtheria, tetanus, acellular pertussis, hepatitis B,
      inactivated poliomyelitis, and Haemophilus influenzae type b (Hib) conjugate
      vaccine, is indicated for primary and booster vaccination of infants. Available
      clinical data from more than a decade of experience with the vaccine indicate
      that primary and booster vaccination with Infanrix hexaTM is a safe and useful
      option for providing protection against the common childhood diseases of
      diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B, and disease caused by
      Hib.

PMID- 22873779
TI  - Modularity as a source of new morphological variation in the mandible of hybrid
      mice.
AB  - BACKGROUND: Hybridization is often seen as a process dampening phenotypic
      differences accumulated between diverging evolutionary units. For a complex trait
      comprising several relatively independent modules, hybridization may however
      simply generate new phenotypes, by combining into a new mosaic modules inherited
      from each parental groups and parts intermediate with respect to the parental
      groups. We tested this hypothesis by studying mandible size and shape in a set of
      first and second generation hybrids resulting from inbred wild-derived laboratory
      strains documenting two subspecies of house mice, Musmusculus domesticus and
      Musmusculus musculus. Phenotypic variation of the mandible was divided into
      nested partitions of developmental, evolutionary and functional modules. RESULTS:
      The size and shape of the modules were differently influenced by hybridization.
      Some modules seemed to be the result of typical additive effects with hybrids
      intermediate between parents, some displayed a pattern expected in the case of
      monogenic dominance, whereas in other modules, hybrids were transgressive. The
      result is interpreted as the production of novel mandible morphologies. Beyond
      this modularity, modules in functional interaction tended to display significant
      covariations. CONCLUSIONS: Modularity emerges as a source of novel morphological
      variation by its simple potential to combine different parts of the parental
      phenotypes into a novel offspring mosaic of modules. This effect is partly
      counterbalanced by bone remodeling insuring an integration of the mosaic mandible
      into a functional ensemble, adding a non-genetic component to the production of
      transgressive phenotypes in hybrids.

PMID- 22873780
TI  - Tungsten toxicity, bioaccumulation, and compartmentalization into organisms
      representing two trophic levels.
AB  - Metallic tungsten has civil and military applications and was considered a green
      alternative to lead. Recent reports of contamination in drinking water and soil
      have raised scrutiny and suspended some applications. This investigation employed
      the cabbage  Brassica oleracae  and snail  Otala lactea  as models to determine
      the toxicological implications of sodium tungstate and an aged tungsten powder
      spiked soil containing monomeric and polymeric tungstates. Aged soil bioassays
      indicated cabbage growth was impaired at 436 mg of W/kg, while snail survival was
      not impacted up to 3793 mg of W/kg. In a dermal exposure, sodium tungstate was
      more toxic to the snail, with a lethal median concentration of 859 mg of W/kg.
      While the snail significantly bioaccumulated tungsten, predominately in the
      hepatopancreas, cabbage leaves bioaccumulated much higher concentrations.
      Synchrotron-based mapping indicated the highest levels of W were in the veins of
      cabbage leaves. Our results suggest snails consuming contaminated cabbage
      accumulated higher tungsten concentrations relative to the concentrations
      directly bioaccumulated from soil, indicating the importance of robust trophic
      transfer investigations. Finally, synchrotron mapping provided evidence of
      tungsten in the inner layer of the snail shell, suggesting potential use of snail
      shells as a biomonitoring tool for metal contamination.

PMID- 22873781
TI  - Cervical cancer screening in the United States, 1993-2010: characteristics of
      women who are never screened.
AB  - BACKGROUND: Regular Pap test screening has contributed to decreasing cervical
      cancer incidence and mortality over the past decades, yet half of the women
      diagnosed with cervical cancer have never had a Pap test. Our study aims to
      examine the cervical cancer screening rate, identify socioeconomic and
      demographic risk factors associated with adult women who have never had a Pap
      test, and examine the relationship of screening with use of related health
      services. METHODS: Using Behavioral Risk Factor Surveillance System data (1993
      2010), a multivariable survey logistic regression model was fitted to estimate
      odds ratios for associations between risk factors and the outcome of never
      screened. RESULTS: Between 1993 and 2010, 81.3% of respondents reported they had
      a Pap test within 3 years; 6.2% were never screened. For women who had a recent
      checkup, 5.5% were never screened. Among women who had a hysterectomy, 69.4% had
      a Pap test within 3 years. The multivariable analysis showed that age,
      race/ethnicity, education, annual household income, never married, and currently
      uninsured were significantly (p<0.001) associated with never screened.
      CONCLUSIONS: Screening programs accompanied by adequate treatment options should
      target women at high risk for never being screened, which could decrease cervical
      cancer incidence and mortality.

PMID- 22873783
TI  - Patients' views on changes in doctor-patient communication between 1982 and 2001:
      a mixed-methods study.
AB  - BACKGROUND: Doctor-patient communication has been influenced over time by factors
      such as the rise of evidence-based medicine and a growing emphasis on patient
      centred care. Despite disputes in the literature on the tension between evidence
      based medicine and patient-centered medicine, patients' views on what constitutes
      high quality of doctor-patient communication are seldom an explicit topic for
      research. The aim of this study is to examine whether analogue patients (lay
      people judging videotaped consultations) perceive shifts in the quality of doctor
      patient communication over a twenty-year period. METHODS: Analogue patients (N =
      108) assessed 189 videotaped general practice consultations from two periods
      (1982-1984 and 2000-2001). They provided ratings on three dimensions (scale 1-10)
      and gave written feedback. With a mixed-methods research design, we examined
      these assessments quantitatively (in relation to observed communication coded
      with RIAS) and qualitatively. RESULTS: 1) The quantitative analyses showed that
      biomedical communication and rapport building were positively associated with the
      quality assessments of videotaped consultations from the first period, but not
      from the second. Psychosocial communication and personal remarks were related to
      positive quality assessments of both periods; 2) the qualitative analyses showed
      that in both periods, participants provided the same balance between positive and
      negative comments. Listening, giving support, and showing respect were considered
      equally important in both periods. We identified shifts in the participants'
      observations on how GPs explained things to the patient, the division of roles
      and responsibilities, and the emphasis on problem-focused communication (first
      period) versus solution-focused communication (last period). CONCLUSION: Analogue
      patients recognize shifts in the quality of doctor-patient communication from two
      different periods, including a shift from problem-focused communication to
      solution-focused communication, and they value an egalitarian doctor-patient
      relationship. The two research methods were complementary; based on the
      quantitative analyses we found shifts in communication, which we confirmed and
      specified in our qualitative analyses.

PMID- 22873782
TI  - Arachidonic acid metabolites in pathogenic yeasts.
AB  - Although most of what is known about the biology and function of arachidonic acid
      metabolites comes from the study of mammalian biology, these compounds can also
      be produced by lower eukaryotes, including yeasts and other fungi. It is also in
      this group of organisms that the least is known about the metabolic pathways
      leading to the production of these compounds as well as the functions of these
      compounds in the biology of fungi and yeasts. This review will deal with the
      discovery of oxylipins from polyunsaturated fatty acids, and more specifically
      the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic
      acid, prostaglandin F2alpha and prostaglandin E2, in yeasts starting in the early
      1990s. This review will also focus on what is known about the metabolic pathways
      and/or proteins involved in the production of these compounds in pathogenic
      yeasts. The possible roles of these compounds in the biology, including the
      pathology, of these organisms will be discussed.

PMID- 22873784
TI  - Analysis of lipids: metal oxide laser ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      used for lipid analysis; however, one of the drawbacks of this technique is
      matrix interference peaks at low masses. Metal oxide surfaces are described here
      for direct, matrix-free analysis of small (MW < 1000 Da) lipid compounds, without
      interferences in the resulting spectra from traditional matrix background peaks.
      Spectra from lipid standards produced protonated and sodiated molecular ions.
      More complex mixtures including vegetable oil shortening and lipid extracts from
      bacterial and algal sources provided similar results. Mechanistic insight into
      the mode of ionization from surface spectroscopy, negative ion mass spectrometry,
      and stable isotope studies is also presented. The metal oxide system is compared
      to other reported matrix-free systems.

PMID- 22873785
TI  - Toward fabric-based flexible microfluidic devices: pointed surface modification
      for pH sensitive liquid transport.
AB  - Microfluidic fiber channels with switchable water transport are fabricated in
      flexible textile PET/PP materials using a preprogrammed yarn-based fabric and a
      yarn-selective surface modification method. The developed robust and scalable
      fabrication method is based on the selective functionalization of the PET yarns
      with an epoxide-containing polymer that is then followed by grafting patterns of
      different pH-sensitive polymers PAA [poly(acrylic acid) ] and P2VP [poly(2-vinyl
      pyridine)]. The selective functionalization of the fabric yields an array of
      amphiphilic channels that are constrained by hydrophobic PP boundaries. Aqueous
      solutions are transported in the amphiphilic channels by capillary forces where
      the direction of the liquid transport is defined by pH-response of the grafted
      polymers. The channels are fed with liquid through hydrophilic, pH insensitive
      PEG [polyethylene glycol] ports. The combination of the PAA and P2VP patterns in
      the amphiphilic channels is used to create pH-sensitive elements that redirect
      aqueous liquids toward PAA channels at pH > 4 and toward both PAA and P2VP
      channels at pH < 4. The system of pH-selective channels in the developed textile
      based microfluidic chip could find analytical applications and can be used for
      smart cloth.

PMID- 22873786
TI  - Coupling of methyl ketones and primary or secondary amines leading to alpha
      ketoamides.
AB  - A metal-free oxidative coupling of methyl ketones and primary or secondary amines
      to alpha-ketoamides has been developed. Four intermediates, alpha-iodoketone,
      alpha-aminoketone, iminium intermediate, and alpha-hydroxy amine have been
      identified through a series of control experiments. The atom-economic methodology
      can be scaled-up, tolerates a variety of functional groups, and is operationally
      simple.

PMID- 22873787
TI  - To tweet or to retweet? That is the question for health professionals on twitter.
AB  - Guided by the MAIN model ( Sundar, 2008 ), this study explored the effects of
      three interface cues conveying source attributes on credibility of health
      messages in Twitter: authority cue (whether a source is an expert or not),
      bandwagon cue (the number of followers that a source has-large vs. small), and
      source proximity cue (distance of messages from its original source-tweet vs.
      retweet). A significant three-way interaction effect on perceived credibility of
      health content was found, such that when a professional source with many
      followers tweets, participants tend to perceive the content to be more credible
      than when a layperson source with many followers tweets. For retweets, however,
      the exact opposite pattern was found. Results also show that for tweets, content
      credibility was significantly associated with the perceived expertise of proximal
      source, whereas for retweets, it was associated with the perceived
      trustworthiness of proximal source. Theoretical and practical implications are
      discussed.

PMID- 22873789
TI  - Everolimus  for the treatment of pancreatic neuroendocrine tumors.
AB  - INTRODUCTION: Pancreatic neuroendocrine tumors (PNET) represent the second most
      common primary malignancy of the pancreas. Until recently, therapeutic options
      for advanced PNET have been limited. AREAS COVERED: A recently published Phase
      III clinical trial demonstrated striking therapeutic activity of the mTOR
      inhibitor everolimus in advanced PNET and led to its approval for this indication
      by the FDA. This review discusses this landmark discovery in the context of
      currently available therapeutic options, pathophysiology and molecular genetics
      of PNET. EXPERT OPINION: The approval of everolimus for the treatment of PNET
      marks a major step forward in the clinical management of this disease and
      represents a notable example of the successful translation of a targeted therapy
      that was initially developed based on findings at the lab bench, into everyday
      clinical practice. These results encourage hopes that the overall therapeutic
      efficacy of such approaches can be further enhanced by the introduction of
      combinatorial regimens, simultaneously targeting more than one oncogenic
      signaling pathway, as well as by stratification of patients based on the
      individual genetic setup of their tumors.

PMID- 22873788
TI  - Incorporation of CC steps into Z-DNA: interplay between B-Z junction and Z-DNA
      helical formation.
AB  - The left-handed DNA structure, Z-DNA, is believed to play important roles in gene
      expression and regulation. Z-DNA forms sequence-specifically with a preference
      for sequences rich in pyrimidine/purine dinucleotide steps. In vivo, Z-DNA is
      generated in the presence of negative supercoiling or upon binding proteins that
      absorb the high energetic cost of the B-to-Z transition, including the creation
      of distorted junctions between B-DNA and Z-DNA. To date, the sequence preferences
      for the B-to-Z transition have primarily been studied in the context of sequence
      repeats lacking B-Z junctions. Here, we develop a method for characterizing
      sequence-specific preferences for Z-DNA formation and B-Z junction localization
      within heterogeneous DNA duplexes that is based on combining 2-aminopurine
      fluorescence measurements with a new quantitative application of circular
      dichroism spectroscopy for determining the fraction of B- versus Z-DNA. Using
      this approach, we show that at least three consecutive CC dinucleotide steps,
      traditionally thought to disfavor Z-DNA, can be incorporated within heterogeneous
      Z-DNA containing B-Z junctions upon binding to the Zalpha domain of the RNA
      adenosine deaminase protein. Our results indicate that the incorporation of CC
      steps into Z-DNA is driven by favorable sequence-specific Z-Z and B-Z stacking
      interactions as well as by sequence-specific energetics that localize the
      distorted B-Z junction at flexible sites. Together, our results expose higher
      order complexities in the Z-DNA code within heterogeneous sequences and suggest
      that Z-DNA can in principle propagate into a wider range of genomic sequence
      elements than previously thought.

PMID- 22873790
TI  - Enhanced photoluminescence of porous silicon nanoparticles coated by
      bioresorbable polymers.
AB  - A significant enhancement of the photoluminescence (PL) efficiency is observed
      for aqueous suspensions of porous silicon nanoparticles (PSiNPs) coated by
      bioresorbable polymers, i.e., polylactic-co-glycolic acid (PLGA) and polyvinyl
      alcohol (PVA). PSiNPs with average size about 100 nm prepared by mechanical
      grinding of electrochemically etched porous silicon were dispersed in water to
      prepare the stable suspension. The inner hydrophobic PLGA layer prevents the
      PSiNPs from the dissolution in water, while the outer PVA layer makes the PSiNPs
      hydrophilic. The PL quantum yield of PLGA/PVA-coated PSiNPs was found to increase
      by three times for 2 weeks of the storage in water. The observed effect is
      explained by taking into account both suppression of the dissolution of PSiNPs in
      water and a process of the passivation of nonradiative defects in PSiNPs. The
      obtained results are interesting in view of the potential applications of PSiNPs
      in bioimaging.

PMID- 22873791
TI  - Histone deacetylase inhibitor trichostatin A promotes the osteogenic
      differentiation of rat adipose-derived stem cells by altering the epigenetic
      modifications on Runx2 promoter in a BMP signaling-dependent manner.
AB  - Adult stem cells reside in many types of tissues and adult stem cell-based
      regenerative medicine holds great promise for repair of diseased tissues.
      Recently, adipose-derived stem cells (ADSCs) were found to be an appealing
      alternative to bone marrow stem cells (BMSCs) for tissue-engineered bone
      regeneration. Compared with BMSCs, ADSCs can be easily and abundantly available
      from adipose tissue. However, our previous study has discovered an important
      phenomenon that BMSCs have greater osteogenic potential than ADSCs in vitro. In
      this study, we aimed to explore its mechanism and improve the osteogenic
      potential of ADSCs for bone tissue regeneration. It has been reported that the
      epigenetic states could contribute to lineage-specific differentiation of adult
      stem cells. We observed that the epigenetic changes of BMSCs were much greater
      compared with ADSCs after a 3-day osteogenic induction. Runt-related
      transcription factor 2 (Runx2) is essential for osteoblast differentiation and
      bone formation. We found that BMSCs underwent more obvious epigenetic changes on
      the Runx2 promoter than ADSCs after osteogenic induction. These results suggest
      the epigenetic regulation involvement in Runx2 expression, and thus osteogenesis.
      We subsequently used a histone deacetylase inhibitor, trichostatin A (TSA), to
      promote the osteogenesis capacity of ADSCs. The results showed that TSA promoted
      rat ADSCs osteogenic differentiation by altering the epigenetic modifications on
      the Runx2 promoter in a bone morphogenetic protein signaling-dependent manner.

PMID- 22873793
TI  - Electron microscopic study on aerosol-assisted synthesis of aluminum
      organophosphonates using flexible colloidal PS-b-PEO templates.
AB  - A wide variety of synthetic approaches from homogeneous precursor solutions have
      so far been developed for precise structural design of materials in multiscale.
      In organic templating approaches for porous materials design, we have recently
      developed a new approach to fabricate colloidal polystyrene-block
      poly(oxyethylene) (PS-b-PEO) templated large pores that can be controlled in
      thick films of aluminum organophosphonate (AOP). In this study, we extended this
      approach using colloidal PS-b-PEO aggregates to aerosol-assisted synthesis for
      the fabrication of spherical particles. Structural variations (morphology and
      porous structure) depended on the synthetic conditions, which were mainly
      investigated by using electron microscopies (SEM and TEM). In addition to the
      insight on the colloidal PS-b-PEO templating of spherical pores in AOP spheres,
      it was found that colloidal PS-b-PEO aggregates were flexible for further design
      of pore shape that was strongly affected by external morphology. In this context,
      we proposed this method as flexible colloidal PS-b-PEO templating to fabricate
      unusual macroporous structures during morphological control from precursor
      solutions containing colloidal PS-b-PEO aggregates. The insights will be
      promising for precise construction of unique devices using porous materials
      templated by colloidal organic aggregates. In addition, we found a useful water
      adsorption-desorption behavior over the macroporous AOP bulky powders when the
      macropores were connected through large pores, which is also significant for
      future development of AOP-based porous materials.

PMID- 22873792
TI  - Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of
      oral squamous carcinoma cells.
AB  - BACKGROUND: Oral cancer is a common cancer and a major health problem in the
      Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl
      2 family has been demonstrated to be overexpressed in oral cancers and to predict
      outcome in oral cancer patients treated with definitive radiotherapy. To study
      the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells
      (OSCC), we investigated in the present study, the association of Mcl-1 isoform
      expression with radiosensitivity of OSCC, using siRNA strategy. METHODS: The time
      course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied
      by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell
      lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516
      (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L
      knockdown alone or in combination with ionizing radiation (IR) on cell
      proliferation, apoptosis & clonogenic survival, was investigated in AW8507 &
      AW13516 cells. Further the expression of Mcl-1L protein was assessed in
      radioresistant sublines generated by fractionated ionizing radiation (FIR).
      RESULTS: Three to six fold higher expression of anti-apoptotic Mcl-1L versus pro
      apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post
      irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax
      & Bak and a significant (P < 0.05) reduction in apoptosis was observed in the
      more radioresistant AW8507, AW13516 versus FBM cells, post-IR. The ratios of anti
      to pro-apoptotic proteins were high in AW8507 as compared to FBM. Treatment with
      Mcl-1L siRNA alone or in combination with IR significantly (P < 0.01) increased
      apoptosis viz. 17.3% (IR), 25.3% (siRNA) and 46.3% (IR plus siRNA) and
      upregulated pro-apoptotic Bax levels in AW8507 cells. Combination of siRNA & IR
      treatment significantly (P < 0.05) reduced cell proliferation and clonogenic
      survival of radioresistant AW8507 & AW13516 cells, suggesting a synergistic
      effect of the Mcl-1L siRNA with IR on radiosensitivity. Interestingly, during the
      development of radioresistant sublines using FIR, high expression of Mcl-1L was
      observed. CONCLUSION: Our studies suggest that Mcl-1L isoform has an important
      role in the survival and radioresistance of OSCC and may be a promising
      therapeutic target in oral cancers.

PMID- 22873794
TI  - Manadosterols A and B, sulfonated sterol dimers inhibiting the Ubc13-Uev1A
      interaction, isolated from the marine sponge Lissodendryx fibrosa.
AB  - Two new dimeric sterols, manadosterols A (1) and B (2), were isolated from the
      marine sponge Lissodendryx fibrosa collected in Indonesia. The two compounds are
      comprised of two sulfonated sterol cores connected through the respective side
      chains. Manadosterols A (1) and B (2) inhibited the Ubc13-Uev1A interaction with
      IC(50) values of 0.09 and 0.13 MUM, respectively. They are the second and third
      natural compounds showing inhibitory activities against the Ubc13-Uev1A
      interaction and are more potent than leucettamol A (IC(50), 106 MUM), the first
      such inhibitor, isolated from another marine sponge.

PMID- 22873795
TI  - Radiation induced esophageal adenocarcinoma in a woman previously treated for
      breast cancer and renal cell carcinoma.
AB  - BACKGROUND: Secondary radiation-induced cancers are rare but well-documented as
      long-term side effects of radiation in large populations of breast cancer
      survivors. Multiple neoplasms are rare. We report a case of esophageal
      adenocarcinoma in a patient treated previously for breast cancer and clear cell
      carcinoma of the kidney. CASE PRESENTATION: A 56 year-old non smoking woman, with
      no alcohol intake and no familial history of cancer; followed in the National
      Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented
      on consultation on January 2011 with dysphagia. Breast cancer was treated with
      modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and
      radiotherapy to breast, inner mammary chain and to pelvis as castration. Less
      than a year later, a renal right mass was discovered incidentally. Enlarged
      nephrectomy realized and showed renal cell carcinoma. A local and metastatic
      breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy
      and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable
      disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy
      showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No
      evidence of metastasis was noticed on computed tomography and breast disease was
      controlled. Palliative brachytherapy to esophagus was delivered. Patient
      presented dysphagia due to progressive disease 4 months later. Jejunostomy was
      proposed but the patient refused any treatment. She died on July 2011.
      CONCLUSION: We present here a multiple neoplasm in a patient with no known family
      history of cancers. Esophageal carcinoma is most likely induced by radiation.
      However the presence of a third malignancy suggests the presence of genetic
      disorders.

PMID- 22873797
TI  - Layer number and stacking sequence imaging of few-layer graphene by transmission
      electron microscopy.
AB  - A method based on dark field transmission electron microscopy is developed to
      quantitively investigate the layer number and stacking order of multilayer
      graphene, demonstrated here on multilayer crystalline graphene synthesized by
      chemical vapor deposition. Our results show that the relative intensities of
      first- and second-order diffraction spots and contrast in corresponding dark
      field images are sufficient to identify the layer number and stacking order of
      graphene with layer number up to seven (7) or more with few-nanometer spatial
      resolution.

PMID- 22873796
TI  - Medication effectiveness may not be the major reason for accepting cardiovascular
      preventive medication: a population-based survey.
AB  - BACKGROUND: Shared decision-making and patients' choice of interventions are
      areas of increasing importance, not least seen in the light of the fact that
      chronic conditions are increasing, interventions considered important for public
      health, and still non-acceptance of especially risk-reducing treatments of
      cardiovascular diseases (CVD) is prevalent. A better understanding of patients'
      medication-taking behavior is needed and may be reached by studying the reasons
      why people accept or decline medication recommendations. The aim of this paper
      was to identify factors that may influence people's decisions and reasoning for
      accepting or declining a cardiovascular preventive medication offer. METHODS:
      From a random sample of 4,000 people aged 40-59 years in a Danish population,
      1,169 participants were asked to imagine being at increased risk of
      cardiovascular disease and being offered a preventive medication. After receiving
      'complete' information about effectiveness of the medication they were asked
      whether they would accept medication. Finally, they were asked about reasons for
      the decision. RESULTS: A total of 725 (67%) of 1,082 participants accepted the
      medication offer. Even quite large effects of medication (up to 8 percentage
      points absolute risk reduction) had a smaller impact on acceptance to medication
      than personal experience with cardiovascular disease. Furthermore, increasing age
      of the participant and living with a partner were significantly associated with
      acceptance. Some 45% of the respondents accepting justified their choice as being
      for health reasons, and they were more likely to be women, live alone, have
      higher income and higher education levels. Among those who did not accept the
      medication offer, 56% indicated that they would rather prefer to change
      lifestyle. CONCLUSIONS: Medication effectiveness seems to have a moderate
      influence on people's decisions to accept preventive medication, while factors
      such as personal experience with cardiovascular disease may have an equally
      strong or stronger influence, indicating that practitioners could do well to
      carefully identify the reasons for their patients' treatment decisions.

PMID- 22873798
TI  - In vitro antiviral activity of Brazilian plants (Maytenus ilicifolia and Aniba
      rosaeodora) against bovine herpesvirus type 5 and avian metapneumovirus.
AB  - CONTEXT: Medicinal plants are well known for their use in traditional folk
      medicine as treatments for many diseases including infectious diseases.
      OBJECTIVE: Six Brazilian medicinal plant species were subjected to an antiviral
      screening bioassay to investigate and evaluate their biological activities
      against five viruses: bovine herpesvirus type 5 (BHV-5), avian metapneumovirus
      (aMPV), murine hepatitis virus type 3, porcine parvovirus and bovine respiratory
      syncytial virus. MATERIALS AND METHODS: The antiviral activity was determined by
      a titration technique that depends on the ability of plant extract dilutions (25
      or 2.5 ug/mL) to inhibit the viral induced cytopathic effect and the extracts'
      inhibition percentage (IP). RESULTS: Two medicinal plant species showed potential
      antiviral activity. The Aniba rosaeodora Ducke (Lauraceae) extract had the best
      results, with 90% inhibition of viral growth at 2.5 ug/mL when the extract was
      added during the replication period of the aMPV infection cycle. The Maytenus
      ilicifolia (Schrad.) Planch. (Celastraceae) extracts at a concentration of 2.5
      ug/mL exhibited antiviral activity during the attachment phase of BHV-5 (IP =
      100%). DISCUSSION AND CONCLUSION: The biomonitored fractionation of the active
      extracts from M. ilicifolia and A. rosaeodora could be a potential tool for
      identifying their active compounds and determining the exact mechanism of action.

PMID- 22873799
TI  - Design and development of a novel pH triggered nanoemulsified in-situ ophthalmic
      gel of fluconazole: ex-vivo transcorneal permeation, corneal toxicity and
      irritation testing.
AB  - The objective of the present research was to develop a novel pH triggered
      nanoemulsified in-situ gel (NE-ISG) for ophthalmic delivery of fluconazole (FLZ)
      to enhance the permeation and residence time of the formulation, by overcoming
      the limitations associated with protective ocular barriers. Pseudoternary phase
      diagrams were constructed using capmul MCM (oil phase), tween 80 (surfactant) and
      transcutol P (cosurfactant) to identify the NE region. Nanoemulsions (NE1-NE6) of
      FLZ were prepared by spontaneous emulsification method and evaluated for various
      pharmacotechnical characteristics. NE4 was selected as optimized NE and was
      dispersed in carbopol 934 solution to form nanoemulsified sols (NE-ISG1 to NE
      ISG5) that were expected to convert in to in-situ gels at corneal pH (7.4). The
      optimized NE-ISG was selected on the basis of gelation ability with a residence
      time up to or more than 6 h. Ex-vivo transcorneal permeation study displayed
      significantly higher (p < 0.05) permeation of FLZ from NE-ISG5 (337.67 ug/cm(2))
      and NE4 (419.30 ug/cm(2)) than the commercial eye drops (112.92 ug/cm(2)). Hen's
      egg test-Chorioallantoic membrane (HET-CAM) test with zero score indicated the
      non-irritant property of developed NE-ISG5. Corneal toxicity study revealed no
      visual signs of tissue damage. Hence it can be concluded that NE-ISG5 may offer a
      more intensive treatment of ocular fungal infections due to higher permeation,
      prolonged precorneal residence time and sustained drug release along with higher
      in-vitro efficacy, safety and greater patient compliance.

PMID- 22873800
TI  - The relationship between changes in health behaviour and initiation of lipid
      lowering and antihypertensive medications in individuals at high risk of
      ischaemic heart disease.
AB  - BACKGROUND: It has been hypothesised that health conscious individuals tend to
      take better care of themselves by greater adherence to preventive medications. We
      examined, whether long-term changes in dietary habits and physical activity were
      associated with initiation of lipid-lowering and antihypertensive medications.
      METHODS: The study population consisted of two subsamples from the population
      based cohort Inter99 study (1999-2006) in Copenhagen, Denmark: one with systolic
      blood pressure > 140 mmHg (N = 557) and one with total cholesterol > 7 mmol/L (N
      = 314). At a health examination, individuals completed a questionnaire about
      health behaviour and had their blood pressure and cholesterol measured at
      baseline and after five years. Data on medications were obtained through linkage
      to the Registry of Medical Product Statistics. RESULTS: Positive changes in
      physical activity (odds ratio =3.50; 95% CI 1.23-7.54) and in dietary habits
      (odds ratio = 2.08; 95% CI 1.03-4.21) were associated with an increased
      initiation of lipid-lowering medications. With respect to antihypertensives, no
      association was observed in terms of physical activity, but for diet, a positive
      trend in terms of initiation was observed among those with positive changes in
      dietary habits (odds ratio = 1.58; 95% CI 0.96-2.59). CONCLUSION: Generally, we
      observed health conscious behaviour in terms of increased initiation of
      preventive medications among those who reported positive changes in health
      behaviour. This study therefore suggests that more attention should be given to
      identifying individuals and groups, who are less health conscious and thereby
      less likely to engage in either preventive medications or changes in health
      behaviours.

PMID- 22873801
TI  - Recombinant human thyroid stimulating hormone-assisted radioactive iodine remnant
      ablation in thyroid cancer patients at intermediate to high risk of recurrence.
AB  - BACKGROUND: Multiple studies have demonstrated successful radioactive iodine
      remnant ablation (RRA) following preparation with recombinant human thyroid
      stimulating hormone (rhTSH). Short-term studies in relatively low-risk patients
      have also suggested that rhTSH-stimulated RRA can have an effective adjuvant
      therapy function in destroying residual microscopic thyroid cancer cells.
      However, very few of these studies have included a significant number of
      intermediate or high-risk patients. The goal of this study was to examine
      clinical outcomes after rhTSH stimulated RRA in a larger cohort of thyroid cancer
      patients at higher risk of recurrence and disease-specific mortality. METHODS: A
      retrospective chart review identified 586 thyroid cancer patients prepared for
      RRA with either a thyroid hormone withdrawal (THW) (n=321) or rhTSH preparation
      (n=265). The primary end points included both the best response to initial
      therapy and the clinical status at final follow-up. Clinical outcomes were
      compared within each of the American Thyroid Association (ATA) risk groups (low,
      intermediate, and high) and American Joint Committee on Cancer (AJCC) stages (I
      IV) based on the method of preparation for RRA (THW vs. rhTSH). RESULTS:
      Preparation with rhTSH was more likely to be associated with an excellent
      response to therapy (39.4% for rhTSH vs. 30% for TWH, p=0.03) and fewer
      additional therapies (29% for rhTSH vs. 37% for TWH, p=0.05) than THW. However,
      after a median follow-up period of 9 years, the final clinical outcomes were not
      significantly different with respect to recurrence rates (1.5% for rhTSH vs. 1.2%
      for TWH), likelihood of having persistent disease (46% for rhTSH vs. 48% for THW)
      or likelihood of having no evidence of disease (53% for rhTSH vs. 52% for TWH).
      Furthermore, clinical outcomes were similar between rhTSH and THW preparation
      across all ATA risk groups and AJCC stages. CONCLUSIONS: rhTSH preparation for
      RRA is associated with a small, but statistically significant improvement in an
      initial response to therapy and similar final clinical outcomes across a wide
      range of risk of recurrence and risk of disease-specific mortality. These data
      suggest that rhTSH preparation for RRA can be effectively used in intermediate
      and high-risk patients without known distant metastases.

PMID- 22873802
TI  - Validity of cost and utility results?

PMID- 22873803
TI  - Retrograde labeling and fine structure of olfactory receptor neurons in cat
      sharks.
AB  - Ciliated and microvillar olfactory receptor cells have been reported in many fish
      species, including teleosts and elasmobranchs. Morphological studies have
      suggested that microvillar cells are the only olfactory receptor cells in the
      elasmobranchs; however, there is no direct evidence for this hypothesis. Here we
      used a cat shark (Scyliorhinus torazame) to determine the cell type of the
      olfactory receptor cells in elasmobranchs. Retrograde labeling with a fluorescent
      dye, Dil, labeled only cells in the second layer from the surface of the
      olfactory epithelium, suggesting that ciliated cells located in the surface layer
      are not olfactory receptor cells. In addition, electron microscopic observation
      revealed that the labeled cells in the second layer have a thin dendritic knob
      extending from the cell body to the free surface of the epithelium. A part of the
      dendritic knob facing the mucous layer did not have ciliary structures. These
      results provide evidence that the aciliate cells are the only olfactory receptor
      cells in the cat shark olfactory organ.

PMID- 22873804
TI  - Evolutionary meaning of non-synchronous medusa release and spawning in the most
      advanced bivalve-inhabiting hydrozoan, Eugymnanthea japonica.
AB  - Circadial spawning times of medusa of the bivalve-inhabiting hydrozoans
      Eugymnanthea japonica Kubota and Eutima japonica Uchida are confirmed to be
      morning (possibly sunrise) for the former species and night for the latter.
      Eugymnanthea, with small, short-lived, univoltine medusae, seems to have evolved
      from a form similar to Eutima japonica, with larger, longer-lived, multivoltine
      medusae; the morning spawning of medusae in Eugymnanthea may therefore be a newly
      evolved trait. Medusa release from polyps and spawning of medusae are not
      synchronous in Eugymnanthea japonica. This non-synchrony may represent an
      evolutionarily transitional state leading to the most advanced state, synchrony
      of these two reproductive events, as in certain other ephemeral hydrozoan
      medusae.

PMID- 22873805
TI  - Comparative phylogeography of two crow species: jungle crow Corvus macrorhynchos
      and carrion crow Corvus corone.
AB  - The jungle crow Corvus macrorhynchos Wagler, 1827, and the carrion crow Corvus
      corone L., 1758, are two closely related species with similar ecological
      requirements that occupy wide distribution ranges in the Palearctic. We studied
      patterns of their genetic variation by using sequences of the mitochondrial
      cytochrome b gene. Corvus macrorhynchos demonstrates a low level of variation and
      differentiation throughout its range, except for a highly diverged population of
      Cheju Island (Korea). The haplotype network shows two haplogroups. The island
      group comprises populations of Sakhalin, Hokkaido, Honshu, and Kyushu, while the
      haplotypes of Taiwan and Ryukyu Islands proved to be closer to the mainland
      group, which also includes populations from the Primorye, Khabarovsk, Amur, and
      Magadan regions in the Russian Far East. This pattern allowed us to develop a
      phylogeographic hypothesis regarding the two modes of settling of the island
      populations. Concerning C. corone, the presence of two distinct haplogroups was
      confirmed within the range of C. c. orientalis. Both haplogroups are found within
      the same populations in Kamchatka and North Sakhalin, which implies secondary
      contacts there. Populations of C. corone are found to be rather stable in the
      western parts of its range, while in the Far East populations experienced recent
      growth, as was observed for C. macrorhynchos in general. The two species appear
      to have passed through different evolutionary scenarios.

PMID- 22873806
TI  - Altitudinal variation in age and body size in Yunnan pond frog (Pelophylax
      pleuraden).
AB  - Large-scale systematic patterns of body size are a basic concern of evolutionary
      biology. Identifying body size variation along altitudinal gradients may help us
      to understand the evolution of life history of animals. In this study, we
      investigated altitudinal variation in body size, age and growth rate in Chinese
      endemic frog, Pelophylax pleuraden. Data sampled from five populations covering
      an altitudinal span of 1413 to 1935 m in Sichuan province revealed that body size
      from five populations did not co-vary with altitudes, not following Bergmann's
      rule. Average adult SVL differed significantly among populations in males, but
      not in females. For both sexes, average adult age differed significantly among
      populations. Post-metamorphic growth rate did not co-vary with altitude, and
      females grew faster than males in all populations. When controlling the effect of
      age, body size did not differ among populations in both sexes, suggesting that
      age did not affect variation in body size among populations. For females, there
      may be other factors, such as the allocation of energy between growth and
      reproduction, that eliminated the effect of age on body size. To our minds, the
      major reason of body size variation among populations in male frogs may be
      related to individual longevity. Our findings also suggest that factors other
      than age and growth rate may contribute to size differences among populations.

PMID- 22873808
TI  - The inheritance of intrasexual dimorphism in female diving beetles (Coleoptera:
      Dytiscidae).
AB  - Many species of Dytiscus diving beetles exhibit intrasexual dimorphism, e.g., the
      elytra is smooth in some females and grooved in others. However, the expression
      of the grooves and whether they are a product of heredity or the environment
      remain unknown. One Japanese species, Dytiscus sharpi sharpi  Wehncke, 1875 ,
      also shows female dimorphism, with grooved and smooth morphs, while D. sharpi
      validus Regimbart, 1899, only has a single morph (the grooved type). A hybrid of
      the two species should therefore provide a means of sorting out how the grooves
      are inherited. We found two independent wetlands of D. sharpi sharpi in Chiba
      Prefecture, Japan. One was a place where a high proportion of grooved females
      lived, and the others had high proportions of smooth females. After five to eight
      generations of beetles from two populations with different proportions of grooved
      females were reared under aquarium conditions constituting a common garden
      design, i.e., water temperature, water depth, and presence of a plant for
      oviposition, the differences remained. We mated smooth virgin females of D.
      sharpi sharpi with males of D. sharpi validus to obtain hybrid offspring. The
      elytral traits of the hybrid females produced only grooved forms. These results
      suggested that the female dimorphism is determined by genetics, and that the
      grooved morph was dominant over the smooth one, independent of environmental
      factors. In addition, the hybrid insects did not differ from the two subspecies
      insects in larval survivorship, pupation success, or sex ratio. They also showed
      neither morphological abnormality nor reduced survival.

PMID- 22873807
TI  - Prostaglandin E2 increases both osteoblastic and osteoclastic activity in the
      scales and participates in calcium metabolism in goldfish.
AB  - Using our original in vitro assay system with goldfish scales, we examined the
      direct effect of prostaglandin E2 (PGE2) on osteoclasts and osteoblasts in
      teleosts. In this assay system, we measured the activity of alkaline phosphatase
      (ALP) and tartrate-resistant acid phosphatase (TRAP) as respective indicators of
      each activity in osteoblasts and osteoclasts. ALP activity in scales
      significantly increased following treatment at high concentration of PGE2(10-7
      and 10-6 M) over 6 hrs of incubation. At 18 hrs of incubation, ALP activity also
      significantly increased in the PGE2 (10-9 to 10-6 M)-treated scale. In the case
      of osteoclasts, TRAP activity tended to increase at 6 hrs of incubation, and then
      significantly increased at 18 hrs of incubation by PGE2 (10(-7) to 10-6 M)
      treatment. At 18 hrs of incubation, the mRNA expression of osteoclastic markers
      (TRAP and cathepsin K) and receptor activator of the NF-kappaB ligand (RANKL), an
      activating factor of osteoclasts expressed in osteoblasts, increased in PGE2
      treated-scales. Thus, PGE2 acts on osteoblasts, and then increases the
      osteoclastic activity in the scales of goldfish as it does in the bone of
      mammals. In an in vivo experiment, plasma calcium levels and scale TRAP and ALP
      activities in the PGE2-injencted goldfish increased significantly. We conclude
      that, in teleosts, PGE2 activates both osteoblasts and osteoclasts and
      participates in calcium metabolism.

PMID- 22873809
TI  - The repertoire of chemical defense genes in the coral Acropora digitifera genome.
AB  - Scleractinian corals are of fundamental ecological significance in tropical and
      sub-tropical shallow water. This ecological success is attributed to their
      ability of formation of obligate endosymbioses with dinoflagellates of the genus
      Symbiodinium. Nevertheless, approximately one-third of reef-building coral
      species are critically endangered and the remainder are under threat from the
      effects of climate change and local impacts. Molecular and cellular mechanisms
      involved in stress responses and the establishment and collapse of the symbiosis
      are therefore an urgent subject of research. Metazoans possess large numbers of
      genes that participate in response to environmental stressors, and chemical
      defense genes included P450 and other oxidases, various conjugating enzymes, ATP
      dependent efflux transporters, oxidative detoxification proteins, as well as
      transcription factors that regulate these genes. Here we searched those genes in
      recently decoded the coral Acropora digitifera genome. We found that this genome
      contains a set of chemical defense genes in numbers comparable with other
      cnidarians and metazoans and that there are some lineagespecific gene family
      expansions in the coral genome. These provide information for future research
      into molecular mechanisms involved in coral stress responses.

PMID- 22873810
TI  - Biogeographical study of plateau pikas Ochotona curzoniae (Lagomorpha,
      Ochotonidae).
AB  - We reconstructed the demographic history of the plateau pika (Ochotona curzoniae)
      on the Qinghai-Tibetan plateau by using genetic variation data obtained from
      spatially distributed populations across much of the plateau. We obtained
      sequence data, including cob (1,140 bp) and D-loop sequences (732 bp), from 144
      individuals at sites ranging from the high-altitude interior to the relatively
      low-altitude northeastern plateau, and identified 37 and 42 unique haplotypes,
      respectively. Phylogenetic analysis and haplotype networks based on the
      individual and the combined datasets of cob and D-loop sequences clustered all
      populations into four well-supported major groups, and the interaction between
      vicariance, dispersal, and habitat fragmentation resulted in the current
      geographical distribution and genetic diversity of O. curzoniae on the plateau.
      Analysis of molecular variance (AMOVA) and mismatch distribution suggested that
      the recent continuous uplifts of the plateau contributed to the radiation and
      diversification of the O. curzoniae populations occurring there.

PMID- 22873811
TI  - Taxonomic study of the Burmoniscus ocellatus complex (Crustacea, Isopoda,
      Oniscidea) in Japan shows genetic diversification in the southern Ryukyus,
      southwestern Japan.
AB  - To clarify the taxonomic status of the Burmoniscus ocellatus complex in Japan, we
      carried out morphological observations and phylogenetic analyses of specimens
      collected from Yonagunijima, Iriomotejima, Ishigakijima, and Miyakojima Islands
      of the southern Ryukyus and from Okinawajima Island of the central Ryukyus in
      southwestern Japan. Observations of the holotypes of Aphiloscia iriomotensis (
      Nunomura, 1986 ), Ap. ishigakiensis ( Nunomura, 1986 ), and Ap. yonakuniensis (
      Nunomura, 1986 ), in addition to the specimens newly collected from the five
      islands, indicated that these specimens belong to the genus Burmoniscus. Analyses
      of five morphological characters of 268 specimens collected from the five islands
      showed that the body size of Okinawajima specimens is distinctly smaller than
      those of the specimens from the southern Ryukyus. The ranges of the five
      morphological characters tended to overlap among the specimens from Yonagunijima,
      Iriomotejima, Ishigakijima and Miyakojima Islands; these morphological characters
      were congruent with those of 6. ocellatus (Verhoeff, 1928). The phylogenetic
      analyses were based on three regions of mitochondrial DNA-COI, 12S rRNA, and 16S
      rRNA-and indicated that the specimens collected from the southern Ryukyus
      constitute a monophyletic group, which is clearly distinct from the clade
      composed of the Okinawajima specimens. These results strongly suggest that Ap.
      iriomotensis, Ap. ishigakiensis, and Ap. yonakuniensis are synonymous with B.
      ocellatus, a species widely distributed in the southern Ryukyus. On the other
      hand, the species from Okinawajima Island in the central Ryukyus is considered to
      be an undescribed Burmoniscus species, which is closely related to but clearly
      distinct from S. ocellatus.

PMID- 22873812
TI  - Cryptic diversity of the eel goby, genus Taenioides (Gobiidae: Amblyopinae), in
      Japan.
AB  - The eel goby, genus Taenioides (Gobiidae: Amblyopinae), inhabits muddy bottoms of
      estuaries or shallow areas of seas in the Indo-Pacific Ocean. Among congeners, T.
      cirratus ( Blyth, 1860 ) has been thought to be distributed in Japan, but
      taxonomic confusions remain as to which scientific names are applicable to
      Japanese Taenioides species, or more fundamentally, how many Taenioides species
      are distributed in Japan, due in part to the rarity of this group in museum
      collections and the morphological similarity among species. To clarify the
      species diversity of the genus Taenioides in Japan, we conducted phylogenetic
      analysis on the basis of partial mitochondrial DNA sequences and morphological
      observation of more than 100 specimens. As a result, four distinct species were
      distinguished from each other, on the basis of both genetic divergences (2.9
      5.7%, 16S rRNA gene) and morphological differences (i.e., degree of development
      of dermal folds on the head, numbers of barbels and vertebrae). Although the
      identifications of four species need additional verifications, they were
      identified as T. anguillaris, T. snyderi, T. gracilis and T. cf. kentalleni, and
      the species name T. cirratus does not seem to be appropriate to any of four
      detected species. Museum collections indicate that the two species, which are
      distributed in the main islands of Japan, were collected frequently and treated
      as a single species. The other two were each collected only from a single
      locality of Okinawa Island in this study, of which one seems to be uncommon
      worldwide as well.

PMID- 22873814
TI  - Pleistocene climate change promoted rapid diversification of aquatic
      invertebrates in Southeast Australia.
AB  - BACKGROUND: The Pleistocene Ice Ages were the most recent geohistorical event of
      major global impact, but their consequences for most parts of the Southern
      hemisphere remain poorly known. We investigate a radiation of ten species of
      Sternopriscus, the most species-rich genus of epigean Australian diving beetles.
      These species are distinct based on genital morphology but cannot be
      distinguished readily by mtDNA and nDNA because of genotype sharing caused by
      incomplete lineage sorting. Their genetic similarity suggests a Pleistocene
      origin. RESULTS: We use a dataset of 3858 bp of mitochondrial and nuclear DNA to
      reconstruct a phylogeny of Sternopriscus using gene and species trees.
      Diversification analyses support the finding of a recent rapid speciation event
      with estimated speciation rates of up to 2.40 species per MY, which is
      considerably higher than the proposed average rate of 0.16 species per MY for
      insects. Additionally, we use ecological niche modeling and analyze data on
      habitat preferences to test for niche divergence between species of the recent
      Sternopriscus radiation. These analyses show that the species can be
      characterized by a set of ecological variables referring to habitat, climate and
      altitude. CONCLUSIONS: Our results suggest that the repeated isolation of
      populations in glacial refugia might have led to divergent ecological adaptations
      and the fixation of morphological traits supporting reproductive isolation and
      therefore may have promoted speciation. The recent Sternopriscus radiation
      fulfills many characteristics of a species flock and would be the first described
      example of an aquatic insect species flock. We argue that the species of this
      group may represent a stage in speciation past the species flock condition
      because of their mostly broad and often non-overlapping ranges and preferences
      for different habitat types.

PMID- 22873815
TI  - Identification of serum proteomic biomarkers for early porcine reproductive and
      respiratory syndrome (PRRS) infection.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the
      most significant swine diseases worldwide. Despite its relevance, serum
      biomarkers associated with early-onset viral infection, when clinical signs are
      not detectable and the disease is characterized by a weak anti-viral response and
      persistent infection, have not yet been identified. Surface-enhanced laser
      desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a
      reproducible, accurate, and simple method for the identification of biomarker
      proteins related to disease in serum. This work describes the SELDI-TOF MS
      analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR,
      asymptomatic Large White piglets at weaning. Sera with comparable and low content
      of hemoglobin (< 4.52 MUg/mL) were fractionated in 6 different fractions by anion
      exchange chromatography and protein profiles in the mass range 1-200 kDa were
      obtained with the CM10, IMAC30, and H50 surfaces. RESULTS: A total of 200
      significant peaks (p < 0.05) were identified in the initial discovery phase of
      the study and 47 of them were confirmed in the validation phase. The majority of
      peaks (42) were up-regulated in PRRSV-positive piglets, while 5 were down
      regulated. A panel of 14 discriminatory peaks identified in fraction 1 (pH = 9),
      on the surface CM10, and acquired at low focus mass provided a serum protein
      profile diagnostic pattern that enabled to discriminate between PRRSV-positive
      and -negative piglets with a sensitivity and specificity of 77% and 73%,
      respectively. CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and
      PRRSV-negative asymptomatic piglets provided a proteomic signature with large
      scale diagnostic potential for early identification of PRRSV infection in weaning
      piglets. Furthermore, SELDI-TOF protein markers represent a refined phenotype of
      PRRSV infection that might be useful for whole genome association studies.

PMID- 22873816
TI  - Endoscopic stenting for hilar cholangiocarcinoma: efficacy of unilateral and
      bilateral placement of plastic and metal stents in a retrospective review of 480
      patients.
AB  - BACKGROUND: Endoscopic biliary drainage of hilar cholangiocarcinoma is
      controversial with respect to the optimal types of stents and the extent of
      drainage. This study evaluated endoscopic palliation in patients with hilar
      cholangiocarcinoma using self-expandable metallic stents (SEMS) and plastic
      stents (PS).We also compared unilateral and bilateral stent placement according
      to the Bismuth classification. METHODS: Data on 480 patients receiving endoscopic
      biliary drainage for hilar cholangiocarcinoma between September 1995 and December
      2010 were retrospectively reviewed to evaluate the following outcome parameters:
      technical success (TS), functional success (FS), early and late complications,
      stent patency and survival. Patients were followed from stent insertion until
      death or stent occlusion. Patients were divided into 3 groups according to the
      Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type >= III).
      RESULTS: The initial stent insertion was successful in 450 (93.8%) patients. TS
      was achieved in 204 (88.3%) patients treated with PS and in 246 (98.8%) patients
      palliated with SEMS (p < 0.001). In the intention-to-treat (ITT) analysis, the FS
      in patients treated with SEMS (97.9%) was significantly higher than in patients
      treated with PS (84.8%) (p < 0.001). Late complications occurred in 115 (56.4%)
      patients treated with PS and 60 (24.4%) patients treated with SEMS (p < 0.001).
      The median duration of stent patency in weeks (w) were as follows: 20 w in
      patients palliated with PS and 27 w in patients treated with SEMS (p < 0.0001).
      In Group 2, the median duration of PS patency was 17 w and 18 w for unilateral
      and bilateral placement, respectively (p = 0.0004); the median duration of SEMS
      patency was 24 w and 29 w for unilateral and bilateral placement, respectively (p
      < 0.0001). Multivariate analysis using the Poisson regression showed that SEMS
      placement (B = 0.48; P < 0.01) and bilateral deployment (B = 0.24; P < 0.01) were
      the only independent prognostic factors associated with stent patency.
      CONCLUSIONS: SEMS insertion for the palliation of hilar cholangiocarcinoma offers
      higher technical and clinical success rates in the ITT analysis as well as lower
      complication rates and a superior cumulative stent patency when compared with PS
      placement in all Bismuth classifications. The cumulative patency of bilateral
      SEMS or PS stents was significantly higher than that of unilateral SEMS or PS
      stents, with lower occlusion rates in Bismuth II patients.

PMID- 22873818
TI  - Emissive osmium(II) complexes supported by N-heterocyclic carbene-based C^C^C
      pincer ligands and aromatic diimines.
AB  - Osmium(II) complexes containing N-heterocyclic carbene (NHC)-based pincer ligand
      1,3-bis(1-methylimidazolin-2-ylidene)phenyl anion (C(1)^C^C(1)) or 1,3-bis(3
      methylbenzimidazolin-2-ylidene)phenyl anion (C(2)^C^C(2)) and aromatic diimine
      (2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), or 4,4'-diphenyl-2,2'
      bipyridine (Ph(2)bpy)) in the form of [Os(C^C^C)(N^N)(CO)](+) have been prepared.
      Crystal structures for these complexes show that the Os-C(NHC) bonds are
      essentially single (Os-C(NHC) distances = 2.079(5)-2.103(7) A). Spectroscopic
      comparisons and time-dependent density functional theory (TD-DFT) calculations
      suggest that the lowest-energy electronic transition associated with these
      complexes (lambda(max) = 493-536 nm, epsilon(max) = (5-10) * 10(3) dm(3) mol(-1)
      cm(-1), solvent = CH(3)CN) originate from a d(pi)(Os(II)) -> pi*(N^N) metal-to
      ligand charge transfer transition, where the d(pi)(Os(II)) and pi*(N^N) levels
      contain significant contribution from the C^C^C ligands. All these complexes are
      emissive in the red-spectral region (674-731 nm) with quantum yields of 10(-4)
      10(-2) and emission lifetimes of around 1-6 MUs. Transient absorption
      spectroscopy and spectroelectrochemical measurements have also been used to probe
      the nature of the emissive excited-states. Overall, this joint experimental and
      theoretical investigation reveals that the C^C^C ligands can be used to modulate
      the photophysical properties of a [Os(N^N)] core via the formation of the hybrid
      [Os + C^C^C] frontier orbitals.

PMID- 22873817
TI  - Mass spectrometric method for determining the uronic acid epimerization in
      heparan sulfate disaccharides generated using nitrous acid.
AB  - Heparan sulfate (HS) glycosaminoglycans (GAGs) regulate a host of biological
      functions. To better understand their biological roles, it is necessary to gain
      understanding about the structure of HS, which requires identification of the
      sulfation pattern as well as the uronic acid epimerization. In order to model HS
      structure, it is necessary to quantitatively profile depolymerization products.
      To date, liquid chromatography-mass spectrometry (LC-MS) methods for profiling
      heparin lyase decomposition products have been shown. These enzymes, however,
      destroy information about uronic acid epimerization. Deaminative cleavage using
      nitrous acid (HONO) is a classic method for GAG depolymerization that retains
      uronic acid epimerization. Several chromatographic methods have been used for
      analysis of deaminative cleavage products. The chromatographic methods have the
      disadvantage that there is no direct readout on the structures producing the
      observed peaks. This report demonstrates a porous graphitized carbon (PGC)-MS
      method for the quantification of HONO generated disaccharides to obtain
      information about the sulfation pattern and uronic acid epimerization. Here, we
      demonstrate the separation and identification of uronic acid epimers as well as
      geometric sulfation isomers. The results are comparable to those expected for
      benchmark HS and heparin samples. The data demonstrate the utility of PGC-MS for
      quantification of HS nitrous acid depolymerization products for structural
      analysis of HS and heparin.

PMID- 22873819
TI  - Ondansetron and granisetron binding orientation in the 5-HT(3) receptor
      determined by unnatural amino acid mutagenesis.
AB  - The serotonin type 3 receptor (5-HT(3)R) is a ligand-gated ion channel found in
      the central and peripheral nervous systems. The 5-HT(3)R is a therapeutic target,
      and the clinically available drugs ondansetron and granisetron inhibit receptor
      activity. Their inhibitory action is through competitive binding to the native
      ligand binding site, although the binding orientation of the drugs at the
      receptor has been a matter of debate. Here we heterologously express mouse 5
      HT(3)A receptors in Xenopus oocytes and use unnatural amino acid mutagenesis to
      establish a cation-pi interaction for both ondansetron and granisetron to
      tryptophan 183 in the ligand binding pocket. This cation-pi interaction
      establishes a binding orientation for both ondansetron and granisetron within the
      binding pocket.

PMID- 22873820
TI  - Dynamic screening of a localized hole during photoemission from a metal cluster.
AB  - : Recent advances in attosecond spectroscopy techniques have fueled the
      interest in the theoretical description of electronic processes taking place in
      the subfemtosecond time scale. Here we study the coupled dynamic screening of a
      localized hole and a photoelectron emitted from a metal cluster using a semi
      classical model. Electron density dynamics in the cluster is calculated with time
      dependent density functional theory, and the motion of the photoemitted electron
      is described classically. We show that the dynamic screening of the hole by the
      cluster electrons affects the motion of the photoemitted electron. At the very
      beginning of its trajectory, the photoemitted electron interacts with the cluster
      electrons that pile up to screen the hole. Within our model, this gives rise to a
      significant reduction of the energy lost by the photoelectron. Thus, this is a
      velocity-dependent effect that should be accounted for when calculating the
      average losses suffered by photoemitted electrons in metals.

PMID- 22873821
TI  - Ulipristal acetate and its role in emergency contraception: a comment.
AB  - The use of selective progesterone modulators (SRMs) has been investigated
      extensively over the last few years. Ulipristal acetate (UPA) is an selective
      progesterone receptor modulator (SPRM) which has been in use since 2010 as an
      effective alternative emergency contraception (EC) regimen to Levonorgestrel
      (LNG). It acts by inhibiting ovulation and delaying implantation. Its
      effectiveness is active up to 120 h after sexual intercourse. UPA is safe and has
      a good tolerability profile. Health care practitioners should inform women of all
      reproductive ages that UPA is an effective alternative agent for those who are
      dissatisfied with other means of EC, and its activity of up to 120 h after sexual
      intercourse should also be highlighted.

PMID- 22873822
TI  - H3K9me-enhanced DNA hypermethylation of the p16INK4a gene: an epigenetic
      signature for spontaneous transformation of rat mesenchymal stem cells.
AB  - To explore the mechanisms underlying spontaneous transformation of mesenchymal
      stem cells (MSCs), changes in senescence-associated molecules, particularly the
      epigenetic modification of the p16(INK4a) gene, including histone H3 lysine 27/9
      methylation (H3K27/9me) and DNA methylation, were investigated in cultured adult
      rat bone marrow MSCs at different stages during the transformation process. It
      was shown that the MSCs underwent replicative senescence after 24 to 25
      population doublings, characterized by positive staining for senescence
      associated beta-galactosidase, increased expression of p16(INK4a) and p21, and
      downregulated phosphorylation of Rb. The upregulation of p16(INK4a) was
      associated with decreased expression of enhancer of the zeste homolog 2 (Ezh2),
      and reduced levels of H3K27me and DNA methylation in the p16(INK4a) gene. At week
      4 of senescence, reproliferating cells emerged among the senescent MSCs. These
      senescence-escaped MSCs lost their senescence-related markers (including
      p16(INK4a)) and became highly proliferative. In addition to H3K27me, another H3
      modification pattern, H3K9me, appeared in the p16(INK4a) gene, accompanied by an
      enhanced DNA methylation. With continued culture, the senescence-escaped MSCs did
      not show any sign of growth arrest and gained the capacity for anchorage
      independent growth. These immortalized (transformed) MSCs showed further enhanced
      DNA methylation of the p16(INK4a) gene by increased H3K9me. Ezh2 knockdown with
      shRNA eliminated H3K27me-mediated DNA methylation of the p16(INK4a) gene in
      presenescent MSCs, but had no effect on H3K9me-enhanced DNA hypermethylation in
      the cells after senescence escape. These findings identify an Ezh2- and H3K27me
      independent, but H3K9me-enhanced, DNA hypermethylation of the p16(INK4a) gene,
      which might be an epigenetic signature for MSC spontaneous transformation.

PMID- 22873823
TI  - Gastroduodeno-plasty performed by distal gastric transection.- A new technique
      for large duodenal defect closure.
AB  - INTRODUCTION: Duodenal ulcer lesions can represent a surgical challenge,
      especially if the duodenal wall is chronically inflamed, the defect exceeds a
      diameter of 3 cm and the ulceration is located in the second part of the
      duodenum. PATIENT AND METHOD: We present the case of a 70-year-old male, who
      suffered from a 3 x 4 cm duodenal defect caused by duodenal pressure necrosis due
      to a 12.5 x 5.5 x 5 cm gallstone. Additionally, this stone caused intestinal
      obstruction (Bouveret's syndrome) and bleeding with signs of shock. Besides the
      gallstone extraction, the common bile duct was drained by a T-tube and the
      duodenal defect closure was performed by a gastroduodeno-plasty and Bilroth II
      gastroenterostomy. The postoperative phase was uneventful. The reconstructed
      duodenum was endoscopically accessible and showed no pathological findings on
      follow-up. CONCLUSION: The reconstruction of a large defect (> 3 cm) of the
      second part of the duodenum is safely feasible by a gastroduodeno-plasty. The
      critical gastroduodenal anastomosis can be protected by duodenal decompression,
      achieved by placing a T-tube in the common bile duct.

PMID- 22873824
TI  - Halicloic acids A and B isolated from the marine sponge Haliclona sp. collected
      in the Philippines inhibit indoleamine 2,3-dioxygenase.
AB  - Two new merohexaprenoids, halicloic acids A (1) and B (2), have been isolated
      from the marine sponge Haliclona (Halichoclona) sp. collected in the Philippines.
      The glycolic acids 1 and 2 slowly decomposed during acquisition of NMR data to
      aldehydes 3 and 4, respectively, via an oxidative decarboxylation. Halicloic acid
      B (2) has the new rearranged "haliclane" meroterpenoid carbon skeleton. The
      halicloic acids 1 and 2 are indoleamine 2,3-dioxygenase inhibitors that are
      significantly more active than the decomposition products 3 and 4.

PMID- 22873825
TI  - The impact of benign gene expression classifier test results on the
      endocrinologist-patient decision to operate on patients with thyroid nodules with
      indeterminate fine-needle aspiration cytopathology.
AB  - BACKGROUND: Seventy-five percent of thyroid nodules with indeterminate fine
      needle aspiration (FNA) cytology are found to be benign postoperatively. A novel
      genomic test, the Afirma gene expression classifier (AGEC), has been available
      for clinical use in the United States, since late 2010. In 2010, two modest-sized
      validation studies showed that the AGEC could identify a benign gene expression
      signature in indeterminate cytology thyroid FNA samples with a negative
      predictive value >95%. The objective of this study was to evaluate how the AGEC
      impacted the joint decision of the endocrinologist and patient to operate when
      FNA cytology was indeterminate, but the AGEC reading of the nodule was benign.
      METHODS: In this cross-sectional cohort study, data were contributed
      retrospectively by 51 endocrinologists at 21 practice sites that had previously
      obtained >=3 benign AGEC readings in >=1 cm nodules with indeterminate FNA
      cytology readings. Information regarding demographic data, nodule size and
      location, decision to operate, surgery type (hemithyroidectomy [HT] or total
      thyroidectomy [TT]), and reason for recommending surgery was retrospectively
      collected. RESULTS: Compared to a 74% previous historical rate of surgery for
      cytologically indeterminate nodules, the operative rate fell to 7.6% during the
      period that AGEC were obtained in the clinical practices, a highly significant
      reduction in the decision to operate (p<0.001). The rate of surgery on
      cytologically indeterminate nodules that were benign by the AGEC reading did not
      differ from the historically reported rate of operation on cytologically benign
      nodules (p=0.41). The four primary reasons reported by the physicians for
      operating on nodules with a benign AGEC reading, in descending order: large
      nodule size (46.4%), symptomatic nodules (25.0%), rapidly growing nodules
      (10.7%), or a second suspicious or malignant nodule in the same patient (10.7%).
      These reasons are concordant with those typically given for operation on
      cytologically benign nodules. CONCLUSIONS: In a substantial group of medical
      practices, obtaining an AGEC test in patients with cytologically indeterminate
      nodules was associated with a striking reduction in the rate of diagnostic
      thyroidectomy. Approximately, one surgery was avoided for every two AGEC tests
      run on thyroid FNAs with indeterminate cytology.

PMID- 22873826
TI  - Biosynthesis of poly[(R)-3-hydroxyalkanoate] copolymers with controlled repeating
      unit compositions and physical properties.
AB  - As applications for biodegradable and biologically produced poly[(R)-3
      hydroxyalkanoates] (PHAs) grow into more specialized areas, the need to precisely
      control the repeating unit composition and consequently the physical properties
      of these polymers has become essential. A previous study reported our development
      of Escherichia coli LSBJ in order to produce PHA polymers composed of single
      repeating units ranging from 4 to 12 carbon atoms. This investigation expands the
      scope of our effort toward controlling the repeating unit composition of a
      variety of PHA copolymers. The sizes for the repeating units within the
      copolymers were modulated by feeding specific ratios of fatty acids with defined
      carbon lengths to E. coli LSBJ, which resulted in defined mole ratios for the
      repeating units. Various physical properties of the copolymers (including the
      Young's modulus, elongation to break, and glass-transition temperature) were
      shown to be strongly dependent upon the mole ratios of repeating units. This work
      demonstrates that copolymers of PHAs with repeating units from 4 to 12 carbons
      can be incorporated accurately to obtain any desired mole ratio within the PHA
      copolymers. Our methodology may thus be extended to generate tailor-made PHA
      copolymers with prescribed values for key sets of physical properties.

PMID- 22873827
TI  - Pharmacometabonomic characterization of xenobiotic and endogenous metabolic
      phenotypes that account for inter-individual variation in isoniazid-induced
      toxicological response.
AB  - An NMR-based pharmacometabonomic approach was applied to investigate inter-animal
      variation in response to isoniazid (INH; 200 and 400 mg/kg) in male Sprague
      Dawley rats, alongside complementary clinical chemistry and histopathological
      analysis. Marked inter-animal variability in central nervous system (CNS)
      toxicity was identified following administration of a high dose of INH, which
      enabled characterization of CNS responders and CNS non-responders. High
      resolution post-dose urinary 1H NMR spectra were modeled both by their xenobiotic
      and endogenous metabolic information sets, enabling simultaneous identification
      of the differential metabolic fate of INH and its associated endogenous metabolic
      consequences in CNS responders and CNS non-responders. A characteristic
      xenobiotic metabolic profile was observed for CNS responders, which revealed
      higher urinary levels of pyruvate isonicotinylhydrazone and beta-glucosyl
      isonicotinylhydrazide and lower levels of acetylisoniazid compared to CNS non
      responders. This suggested that the capacity for acetylation of INH was lower in
      CNS responders, leading to increased metabolism via conjugation with pyruvate and
      glucose. In addition, the endogenous metabolic profile of CNS responders revealed
      higher urinary levels of lactate and glucose, in comparison to CNS non
      responders. Pharmacometabonomic analysis of the pre-dose 1H NMR urinary spectra
      identified a metabolic signature that correlated with the development of INH
      induced adverse CNS effects and may represent a means of predicting adverse
      events and acetylation capacity when challenged with high dose INH. Given the
      widespread use of INH for the treatment of tuberculosis, this pharmacometabonomic
      screening approach may have translational potential for patient stratification to
      minimize adverse events.

PMID- 22873828
TI  - A systematic review of economic evaluations of cardiac rehabilitation.
AB  - BACKGROUND: Cardiac rehabilitation (CR), a multidisciplinary program consisting
      of exercise, risk factor modification and psychosocial intervention, forms an
      integral part of managing patients after myocardial infarction (MI),
      revascularization surgery and percutaneous coronary interventions, as well as
      patients with heart failure (HF). This systematic review seeks to examine the
      cost-effectiveness of CR for patients with MI or HF and inform policy makers in
      Singapore on published cost-effectiveness studies on CR. METHODS: Electronic
      databases (EMBASE, MEDLINE, NHS EED, PEDro, CINAHL) were searched from inception
      to May 2010 for published economic studies. Additional references were identified
      through searching bibliographies of included studies. Two independent reviewers
      selected eligible publications based on the inclusion/exclusion criteria. Quality
      assessment of economic evaluations was undertaken using Drummond's checklist.
      RESULTS: A total of 22 articles were selected for review. However five articles
      were further excluded because they were cost-minimization analyses, whilst one
      included patients with stroke. Of the final 16 articles, one article addressed
      both centre-based cardiac rehabilitation versus no rehabilitation, as well as
      home-based cardiac rehabilitation versus no rehabilitation. Therefore, nine
      studies compared cost-effectiveness between centre-based supervised CR and no CR;
      three studies examined that between centre- and home based CR; one between
      inpatient and outpatient CR; and four between home-based CR and no CR. These
      studies were characterized by differences in the study perspectives, economic
      study designs and time frames, as well as variability in clinical data and
      assumptions made on costs. Overall, the studies suggested that: (1) supervised
      centre-based CR was highly cost-effective and the dominant strategy when compared
      to no CR; (2) home-based CR was no different from centre-based CR; (3) no
      difference existed between inpatient and outpatient CR; and (4) home-based
      programs were generally cost-saving compared to no CR. CONCLUSIONS: Overall, all
      the studies supported the implementation of CR for MI and HF. However, comparison
      across studies highlighted wide variability of CR program design and delivery.
      Policy makers need to exercise caution when generalizing these findings to the
      Singapore context.

PMID- 22873829
TI  - High rate of remissions in chronic myelomonocytic leukemia treated with 5
      azacytidine: results of an Italian retrospective study.

PMID- 22873830
TI  - Intrathecal therapy with rituximab in central nervous system involvement of post
      transplant lymphoproliferative disorder.
AB  - Post-transplant lymphoproliferative disorder (PTLD) caused by Epstein-Barr virus
      (EBV) is a severe complication in high-risk allogeneic hematopoietic stem cell
      transplant (HSCT) recipients. Central nervous system (CNS) involvement of PTLD is
      a very rare event in patients with HSCT. As no established standard therapy in
      CNS-EBV-PTLD is available, the aim of this study was analysis of the safety and
      efficacy of intrathecal rituximab therapy in a group of eight children and
      adolescents with CNS-EBV-PTLD. Seven patients responded to therapy: all clinical
      symptoms and EBV-DNA viral load resolved after a median 2 (range: 1-7) doses of
      rituximab. However, some magnetic resonance imaging (MRI) changes in brain scan
      persisted in two patients. In all patients, except one, no adverse events of the
      therapy were observed. In conclusion, intrathecal rituximab administration seems
      to be an effective and safe method of treatment of CNS-EBV-PTLD in pediatric stem
      cell recipients. We recommend this treatment modality for further investigation.

PMID- 22873831
TI  - Rapid and simple colorimetric assay for screening angiotensin I-converting enzyme
      inhibitors.
AB  - CONTEXT: Angiotensin-converting enzyme (ACE) is one of the main regulators of
      blood pressure through its action on the renin-angiotensin system. ACE inhibitory
      peptides from natural materials inhibit ACE activity and have considerable
      importance as antihypertensive agents. OBJECTIVE: A new chromogenic reaction
      method for determining hippuric acid (HA) and angiotensin I-converting enzyme
      (ACE) inhibitor activity was developed. MATERIALS AND METHODS: This method is
      based on the reaction of HA with p-dimethylaminobenzaldehyde in the presence of
      quinoline, acetate, and acetic anhydride. The red-orange formation product in the
      reaction has a stable absorbance in the visible region and it was determined at
      478 nm. The assay conditions were optimized and by using an ACE concentration of
      12 mU/mL in enzymatic reaction, the method was applied to monitor the IC(50)
      values (the concentration of inhibitor required to inhibit 50% of the ACE
      activity) for captopril and Saurida elongata (Synodontidae) muscle protein
      hydrolyzate. RESULTS: With the proposed method, IC(50) values for captopril and
      Saurida elongata muscle protein hydrolyzate were determined as 0.0123 uM and
      0.1648 mg/mL, respectively. Those results correspond to the IC(50) values of
      0.0109 uM and 0.1820 mg/mL obtained by high-performance liquid chromatography
      (HPLC) method. DISCUSSION AND CONCLUSION: The proposed method is rapid, accurate,
      reproducible and convenient, and suitable for screening ACE inhibitor peptides
      from food materials while it does not require HA extraction from the components
      of the ACE activity assay reaction.

PMID- 22873833
TI  - Ligand recruitment and spin transitions in the solid-state photochemistry of
      Fe(III)TPPCl.
AB  - We report evidence for the formation of long-lived photoproducts following
      excitation of iron(III) tetraphenylporphyrin chloride (Fe(III)TPPCl) in a 1:1
      glass of toluene and CH(2)Cl(2) at 77 K. The formation of these photoproducts is
      dependent on solvent environment and temperature, appearing only in the presence
      of toluene. No long-lived product is observed in neat CH(2)Cl(2) solvent. A 2
      photon absorption model is proposed to account for the power-dependent
      photoproduct populations. The products are formed in a mixture of spin states of
      the central iron(III) metal atom. Metastable six-coordinate high-spin and low
      spin complexes and a five-coordinate high-spin complex of iron(III)
      tetraphenylporphyrin are assigned using structure-sensitive vibrations in the
      resonance Raman spectrum. These species appear in conjunction with resonantly
      enhanced toluene solvent vibrations, indicating that the Fe(III) compound formed
      following photoexcitation recruits a toluene ligand from the surrounding
      environment. Low-temperature transient absorption (TA) measurements are used to
      explain the dependence of product formation on excitation frequency in this
      photochemical model. The six-coordinate photoproduct is initially formed in the
      high-spin Fe(III) state, but population relaxes into both high-spin and low-spin
      state at 77 K. This is the first demonstration of coupling between the optical
      and magnetic properties of an iron-centered porphyrin molecule.

PMID- 22873832
TI  - Oxidative condensations to form benzimidazole-substituted potassium
      organotrifluoroborates.
AB  - A library of benzimidazole-substituted potassium organotrifluoroborates was
      prepared via the condensation of various potassium formyl-substituted aryl- and
      heteroaryltrifluoroborates with aromatic 1,2-diamines under oxidative conditions.
      The efficient Suzuki-Miyaura cross-coupling of products thus formed to various
      aryl and heteroaryl bromides was achieved in good yields. The method allows the
      facile preparation of benzimidazole-containing triaromatic products in two steps
      from simple potassium formyl substituted aryl- or heteroaryltrifluoroborates.

PMID- 22873834
TI  - A new controlled-release liquid delivery system based on diclofenac potassium and
      low molecular weight chitosan complex solubilized in polysorbates.
AB  - A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac
      potassium (DP) was prepared and dispersed in high concentrations of polysorbate
      20, 60 and 80 in water to form a solution which releases its components slowly.
      The formed complex was characterized using different analytical methods. The size
      of the resulted nanoparticles and the effect of tweens on size were followed
      using dynamic light scattering (DLS). The release of DP from this delivery system
      was monitored by altering the molecular weight of chitosan and the type and
      concentration of the polysorbates used. The most suitable preparation consisted
      of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the
      release was followed by the adaptation of USP II apparatus using a cellophane
      bag. This preparation offers a release of up to 24 h. 

PMID- 22873836
TI  - Quality of health news disseminated in the print media in developing countries: a
      case study in Iran.
AB  - BACKGROUND: Mass media play an important role in keeping people up-to-date with
      the latest health news. This study aims at investigating the quality of health
      news disseminated in the print media, its course of production and factors
      affecting its quality. METHODS: In the quantitative section of the study, 410
      health-related news items, published during a six-month span in the Iranian
      public press, underwent content analysis. In the qualitative section, focus group
      discussions were held with journalists, editors-in-chief and news gatekeepers.
      RESULTS: The quantitative phase showed that 18% of the news articles were not fit
      for dissemination in public. The qualitative phase illustrated that multiple
      factors at various levels affect the quality of news, namely poor knowledge,
      inadequate motivations and context-related barriers. CONCLUSIONS: The quality of
      health news reporting is not desirable. Educational interventions need to be
      carried out to raise awareness among researchers and journalists. Also, certain
      steps should be taken to increase motivations and strengthen infrastructures,
      including designing guidelines and monitoring news.

PMID- 22873837
TI  - Practical way to imidazo[4,5-b] and [4,5-c]pyridine-2-ones via cascade
      ureidation/palladium-catalyzed cyclization.
AB  - We developed an efficient one-pot tandem carbamoyl chloride amination and
      palladium-catalyzed intramolecular urea cyclization, which furnished high
      throughput access to imidazo[4,5-b]pyridine-2-one and related imidazo[4,5
      c]pyridine-2-one ring systems. Moderate to excellent yields were reported. 

PMID- 22873838
TI  - Phosph(on/in)ate-bridged vanadium(IV) dimers: synthesis and characterization.
AB  - A series of dinuclear organophosphorus-bridged complexes of the general formula
      {(LVO(MU-O(2)PRR')}(2) [L = eta(5)-cyclopentadienyltris(diethylphosphito
      kappa(1)P) cobaltate(III)] has been synthesized as a structural model for the
      industrially used vanadium phosphate oxidation catalysts. These dimeric species
      contain two vanadium centers in a VO(6) environment bridged by O-P-O units. These
      complexes have been characterized via spectral and magnetic analyses. Structural
      parameters have been analyzed through X-ray diffraction. The dimers generally
      exist in either a cis/cis-anti or retracted chair conformation in the solid
      state. The syntheses, structural, spectral, and magnetic data are presented and
      discussed here.

PMID- 22873835
TI  - Unique aspects of competitive weightlifting: performance, training and
      physiology.
AB  - Weightlifting is a dynamic strength and power sport in which two, multijoint,
      whole-body lifts are performed in competition; the snatch and clean and jerk.
      During the performance of these lifts, weightlifters have achieved some of the
      highest absolute and relative peak power outputs reported in the literature. The
      training structure of competitive weightlifters is characterized by the frequent
      use of high-intensity resistance exercise movements. Varied coaching and training
      philosophies currently exist around the world and further research is required to
      substantiate the best type of training programme for male and female
      weightlifters of various age groups. As competitive weightlifting is contested
      over eight male and seven female body weight categories, the anthropometric
      characteristics of the athletes widely ranges. The body compositions of
      weightlifters are similar to that of athletes of comparable body mass in other
      strength and power sports. However, the shorter height and limb lengths of
      weightlifters provide mechanical advantages when lifting heavy loads by reducing
      the mechanical torque and the vertical distance that the barbell must be
      displaced. Furthermore, the shorter body dimensions coincide with a greater mean
      skeletal muscle cross-sectional area that is advantageous to weightlifting
      performance. Weightlifting training induces a high metabolic cost. Although
      dietary records demonstrate that weightlifters typically meet their required
      daily energy intake, weightlifters have been shown to over consume protein and
      fat at the expense of adequate carbohydrate. The resulting macronutrient
      imbalance may not yield optimal performance gains. Cross-sectional data suggest
      that weightlifting training induces type IIX to IIA fibre-type transformation.
      Furthermore, weightlifters exhibit hypertrophy of type II fibres that is
      advantageous to weightlifting performance and maximal force production. As such,
      the isometric peak force and contractile rate of force development of
      weightlifters is ~15-20% and ~13-16% greater, respectively, than in other
      strength and power athletes. In addition, weightlifting training has been shown
      to reduce the typical sex-related difference in the expression of neuromuscular
      strength and power. However, this apparent sex-related difference appears to be
      augmented with increasing adult age demonstrating that women undergo a greater
      age-related decline in muscle shortening velocity and peak power when compared
      with men. Weightlifting training and competition has been shown to induce
      significant structural and functional adaptations of the cardiovascular system.
      The collective evidence shows that these adaptations are physiological as opposed
      to pathological. Finally, the acute exercise-induced testosterone, cortisol and
      growth hormone responses of weightlifters have similarities to that of following
      conventional strength and hypertrophy protocols involving large muscle mass
      exercises. The routine assessment of the basal testosterone : cortisol ratio may
      be beneficial when attempting to quantify the adaptive responses to weightlifting
      training. As competitive weightlifting is becoming increasingly popular around
      the world, further research addressing the physiological responses and
      adaptations of female weightlifters and younger (i.e. <=17 years of age) and
      older (i.e. >=35 years of age) weightlifters of both sexes is required.

PMID- 22873839
TI  - The impact of irritable bowel syndrome on health-related quality of life: a
      Singapore perspective.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder.
      The prevalence of IBS in Asian countries varies from 2.9% to 15.6%. IBS does not
      result in increased mortality, but is associated with psychological distress and
      disruption of work and sleep. Consequently, the evaluation of health-related
      quality of life (HRQoL) is an important outcome measure for patients with IBS
      since it provides a holistic assessment of the patient's emotional, social and
      physical function. However, some HRQoL tools can be time-consuming to apply. EQ
      5D is a brief HRQoL tool which has been validated in the Western IBS population
      but has thus far not been used in Asia. This study was conducted to determine
      whether persons with self-reported symptoms that met the Rome III criteria for
      IBS had a poorer quality of life than those without these symptoms. We also aimed
      to determine which specific aspects of quality of life were most affected and
      whether any risk factors distinguished those with and without IBS. METHODS: Self
      administered questionnaires which included the Rome III diagnostic questionnaire
      modules for IBS and the EQ-5D questionnaire were obtained from participants of a
      health symposium in Singapore on 31th October 2010. IBS was diagnosed based on
      the Rome III Criteria. The main outcome measure was the EQ-5D index score. The
      relationship between the presence of IBS and the EQ-5D index score, individual
      dimensions of EQ-5D and demographic risk factors were examined. RESULTS: 449
      completed questionnaires were analyzed. The mean EQ-5D index score for IBS was
      0.739 which was a significant reduction compared to non-IBS participants [-0.11
      (95% CI: -0.15 to -0.07), p<0.001]. Multivariate analysis showed that IBS was
      significantly associated with younger age and higher education level. Of the five
      EQ-5D dimensions, IBS sufferers were significantly affected in mobility, anxiety
      or depression, usual activity and pain. There was a "dose related" increase in
      likelihood of having IBS with increased severity of pain and anxiety or
      depression. CONCLUSION: IBS sufferers have significantly poorer quality of life.
      Assessment of HRQoL in IBS using the EQ-5D should be considered in further
      studies and routine clinical practice.

PMID- 22873840
TI  - Responsive wormlike micelles from dynamic covalent surfactants.
AB  - Dynamic covalent chemistry is a powerful tool for the construction of adaptive
      and stimulus-responsive nanosystems. Here we report on the spontaneous formation
      of dynamic covalent wormlike micelles from imine-based gemini surfactants, formed
      upon mixing aqueous solutions of two complementary non-surface-active precursors.
      Resulting from the reversibility of the dynamic covalent imine bond, the wormlike
      micelles can be switched between an isotropic solution and the assembled state,
      triggered by pH and temperature. Thermodynamic modeling of the reaction
      equilibria shows that, although mixtures of single- and double-tailed surfactants
      are formed, it is mainly the double-tailed surfactant that assembles into the
      wormlike micelles.

PMID- 22873841
TI  - High temperature in-situ observations of multi-segmented metal nanowires
      encapsulated within carbon nanotubes by in-situ filling technique.
AB  - Multi-segmented one-dimensional metal nanowires were encapsulated within carbon
      nanotubes (CNTs) through in-situ filling technique during plasma-enhanced
      chemical vapor deposition process. Transmission electron microscopy (TEM) and
      environmental TEM were employed to characterize the as-prepared sample at room
      temperature and high temperature. The selected area electron diffractions
      revealed that the Pd4Si nanowire and face-centered-cubic Co nanowire on top of
      the Pd nanowire were encapsulated within the bottom and tip parts of the
      multiwall CNT, respectively. Although the strain-induced deformation of graphite
      walls was observed, the solid-state phases of Pd4Si and Co-Pd remain even at
      above their expected melting temperatures and up to 1,550 +/- 50 degrees C.
      Finally, the encapsulated metals were melted and flowed out from the tip of the
      CNT after 2 h at the same temperature due to the increase of internal pressure of
      the CNT.

PMID- 22873930
TI  - Evaluation of the efficacy of bendiocarb in indoor residual spraying against
      pyrethroid resistant malaria vectors in Benin: results of the third campaign.
AB  - BACKGROUND: Since 2008, the National Malaria Control Program (NMCP) has been
      engaged in the implementation of indoor residual spraying (IRS) in Benin. The
      first and second round was a success with a drastic decrease of malaria
      transmission in areas under IRS. We present here the results of the third round.
      The purpose of this study was to compare the results of the third round of IRS to
      those achieved during the first two rounds. A second success of IRS will enable
      the Government of Benin to extend the strategy to other areas. METHODS: Mosquito
      collections were carried out in the department of Oueme where the homes of four
      districts were treated with bendiocarb. In these districts, more than 350 000
      inhabitants were protected by IRS. A fifth untreated district served as control.
      In the five districts, mosquito collections were organized to follow the dynamics
      of malaria transmission and possible changes in the behavior of mosquitoes.
      RESULTS: A significant reduction in human biting rate was recorded after the
      third round of IRS, specifically in Adjohoun (89.78%), Dangbo (56.8%) and
      Misserete (93.22%) where an inhabitant received less than 2 bites of An. gambiae
      per night. During this same time, the entomological inoculation rate (EIR)
      declined dramatically in all areas under intervention (74.26% reduction). We also
      noted a significant reduction in longevity, the blood feeding rate of the vectors
      and an increase in exophily induced by bendiocarb on An. gambiae and Mansonia
      spp. CONCLUSION: The present study showed, once again, the effectiveness of
      bendiocarb on anopheles populations resistant to pyrethroids. This product can be
      recommended in combination with other insecticides for the management of vector
      resistance to insecticides.

PMID- 22873932
TI  - EGF and HB-EGF enhance the proliferation of programmable cells of monocytic
      origin (PCMO) through activation of MEK/ERK signaling and improve differentiation
      of PCMO-derived hepatocyte-like cells.
AB  - BACKGROUND: Hepatocyte-like cells (NeoHepatocytes) generated from a peripheral
      blood monocyte-derived stem cell-like cell (the PCMO) are a promising alternative
      for primary hepatocytes in cell transplantation studies to cure liver diseases.
      However, to be therapeutically effective NeoHepatocytes are needed in large
      quantities. It was the aim of the present study to investigate i) whether the
      proportion of actively proliferating NeoHepatocytes can be enhanced by
      supplementing the PCMO differentiation medium (containing M-CSF, IL-3, and human
      serum) with either EGF or HB-EGF and ii) which signaling pathway underlies the
      promitotic effect. RESULTS: EGF and HB-EGF enhanced cell proliferation of PCMOs
      as demonstrated by increased expression of cycle control genes (ABL, ANAPC2,
      CDC2, CDK4, CDK6), phosphorylation of the retinoblastoma protein, and increased
      PCMO cell numbers after stimulation with EGF or HB-EGF. EGF also raised the
      number of monocytes expressing the proliferation marker Ki67. PCMOs expressed the
      EGF receptors EGFR (ERBB1) and ERBB3, and expression of both increased during
      PCMO generation. Phosphoimmunoblotting of PCMOs indicated that both EGF and HB
      EGF activated MEK-1/2 and ERK1/2 in a concentration-dependent fashion with the
      effect of EGF being more prominent. EGF treatment further decreased expression of
      p47phox and increased that of Nanog indicating enhanced dedifferentiation and
      pluripotency, respectively. Treatment with both EGF and HB-EGF resulted in
      NeoHepatocytes with improved functional parameters. CONCLUSIONS: The results
      suggested that the addition of EGF or HB-EGF to PCMO differentiation medium
      superactivates MEK/ERK signaling which then increases both PCMO proliferation,
      number, and functional differentiation of PCMO-derived NeoHepatocytes.

PMID- 22873931
TI  - The carbon starvation response of Aspergillus niger during submerged cultivation:
      insights from the transcriptome and secretome.
AB  - BACKGROUND: Filamentous fungi are confronted with changes and limitations of
      their carbon source during growth in their natural habitats and during industrial
      applications. To survive life-threatening starvation conditions, carbon from
      endogenous resources becomes mobilized to fuel maintenance and self-propagation.
      Key to understand the underlying cellular processes is the system-wide analysis
      of fungal starvation responses in a temporal and spatial resolution. The
      knowledge deduced is important for the development of optimized industrial
      production processes. RESULTS: This study describes the physiological,
      morphological and genome-wide transcriptional changes caused by prolonged carbon
      starvation during submerged batch cultivation of the filamentous fungus
      Aspergillus niger. Bioreactor cultivation supported highly reproducible growth
      conditions and monitoring of physiological parameters. Changes in hyphal growth
      and morphology were analyzed at distinct cultivation phases using automated image
      analysis. The Affymetrix GeneChip platform was used to establish genome-wide
      transcriptional profiles for three selected time points during prolonged carbon
      starvation. Compared to the exponential growth transcriptome, about 50% (7,292)
      of all genes displayed differential gene expression during at least one of the
      starvation time points. Enrichment analysis of Gene Ontology, Pfam domain and
      KEGG pathway annotations uncovered autophagy and asexual reproduction as major
      global transcriptional trends. Induced transcription of genes encoding hydrolytic
      enzymes was accompanied by increased secretion of hydrolases including
      chitinases, glucanases, proteases and phospholipases as identified by mass
      spectrometry. CONCLUSIONS: This study is the first system-wide analysis of the
      carbon starvation response in a filamentous fungus. Morphological, transcriptomic
      and secretomic analyses identified key events important for fungal survival and
      their chronology. The dataset obtained forms a comprehensive framework for
      further elucidation of the interrelation and interplay of the individual cellular
      events involved.

PMID- 22873933
TI  - Why do nursing homes close? An analysis of newspaper articles.
AB  - Using Non-numerical Unstructured Data Indexing Searching and Theorizing (NUD'IST)
      software to extract and examine keywords from text, the authors explored the
      phenomenon of nursing home closure through an analysis of 30 major-market
      newspapers over a period of 66 months (January 1, 1999 to June 1, 2005).
      Newspaper articles typically represent a careful analysis of staff impressions
      via interviews, managerial perspectives, and financial records review. There is a
      current reliance on the synthesis of information from large regulatory databases
      such as the Online Survey Certification And Reporting database, the California
      Office of Statewide Healthcare Planning and Development database, and Area
      Resource Files. Although such databases permit the construction of studies
      capable of revealing some reasons for nursing home closure, they are hampered by
      the confines of the data entered. Using our analysis of newspaper articles, the
      authors are able to add further to their understanding of nursing home closures.

PMID- 22873934
TI  - Electronic access to food and cash benefits.
AB  - The authors' purpose was to examine access to Family Independence Program and
      Food benefits in relation to customer service and an automated helpline. In
      addition, participants identified impediments and limitations to the receipt of
      services. Two hundred forty-four surveys were mailed to recipients of over-the
      counter electronic benefit transfer cards; 58 were returned. The findings
      indicate that when customers (age 21-92) received assistance navigating the
      electronic benefits transfer system from local office staff, they were able to
      obtain benefits successfully. Negative credit/debit card history and touchtone
      phones were related to difficulty using the system. The results suggest that the
      local office and the contracted service provider (automatic helpline) need to
      provide assistance that promotes greater autonomy for the customer to make
      successful transitions to benefits that are delivered electronically.

PMID- 22873935
TI  - Health and social services integration: a review of concepts and models.
AB  - Health and social services integration is particularly relevant for populations
      whose needs span physical health, mental health, housing, and disability
      services, along with others. Veterans, homeless, chronically ill, and aging are
      among those populations. This review examines recent peer-reviewed literature
      about different approaches to services integration, rationales behind those
      approaches, and successes of those approaches, including factors that make them
      succeed or fail. The focus here is on services that cross disciplinary
      boundaries; that is, those that integrate health services with social services,
      health services with mental health services, or one social service with a
      categorically different social service.

PMID- 22873936
TI  - Health of migrants with precarious status: results of an exploratory study in
      Montreal--Part B.
AB  - Increasingly, migrants with precarious status (MPS) are recognized as being
      particularly vulnerable. This exploratory study assesses whether the health of
      MPS in Montreal, Canada, is similar to that reported in the international
      literature (see Health situation of migrants with precarious status: Review of
      the literature and implications for the Canadian context--Part A, Social Work in
      Public Health, 27 (4), 330-344). The results of this study show that, as in other
      parts of the world, MPS in Canada appear to be confronted by multiple obstacles
      to health, many of which are linked to their precarious migration status and its
      impact on living conditions and access to health care. To reduce health
      inequalities, therefore, it is crucial to better understand and address the
      specific needs of this highly vulnerable population.

PMID- 22873937
TI  - Efficiency of health care system in India: an inter-state analysis using DEA
      approach.
AB  - Since independence a massive personnel and public health infrastructure has been
      created in India. However, there is no competition and hardly any choice to the
      poor patients resulting in poor quality services leading to allocative and
      technical inefficiencies. This study uses the data envelopment analysis model to
      assess and compare the efficiency of health system within various states of
      India. It shows the inadequacy of health infrastructure and manpower in the
      inefficient states where poor people are concentrated. Among the determinants of
      efficiency female literacy, poverty level, institutional delivery, and full
      immunization of children are proved to be important factors in explaining
      efficiency of health system in India.

PMID- 22873938
TI  - Do empowerment strategies facilitate knowledge and behavioral change? The impact
      of family health advocacy on health outcomes.
AB  - This study evaluates the impact of a Family Health Advocacy (FHA) intervention on
      46 African American women ages 13 to 35 living in a rural southern community. FHA
      utilizes empowerment strategies to provide education and social support to reduce
      risk factors for poor pregnancy outcomes. Use of a paired t test demonstrated a
      statistically significant difference between pretest and posttest scores in the
      acquisition of knowledge of safer sex practices, alcohol consumption, early
      prenatal care, maternal infection, and nutrition. Behavioral change was not
      realized in the areas of nutrition or behaviors that cause risk of maternal
      infection. Social workers can influence behavioral change for at-risk populations
      by addressing microlevel barriers such as education and resources and macrolevel
      barriers such as advocacy for expanded health and social services.

PMID- 22873939
TI  - Adhesion of mussel foot protein Mefp-5 to mica: an underwater superglue.
AB  - Mussels have a remarkable ability to attach their holdfast, or byssus,
      opportunistically to a variety of substrata that are wet, saline, corroded,
      and/or fouled by biofilms. Mytilus edulis foot protein-5 (Mefp-5) is one of
      several proteins in the byssal adhesive plaque of the mussel M. edulis. The high
      content of 3,4-dihydroxyphenylalanine (Dopa) (~30 mol %) and its localization
      near the plaque-substrate interface have often prompted speculation that Mefp-5
      plays a key role in adhesion. Using the surface forces apparatus, we show that on
      mica surfaces Mefp-5 achieves an adhesion energy approaching E(ad) = ~-14
      mJ/m(2). This exceeds the adhesion energy of another interfacial protein, Mefp-3,
      by a factor of 4-5 and is greater than the adhesion between highly oriented
      monolayers of biotin and streptavidin. The adhesion to mica is notable for its
      dependence on Dopa, which is most stable under reducing conditions and acidic pH.
      Mefp-5 also exhibits strong protein-protein interactions with itself as well as
      with Mefp-3 from M. edulis.

PMID- 22873941
TI  - Update 1 of: strong ionic hydrogen bonds.

PMID- 22873940
TI  - Patient anxiety and concern as predictors for the perceived quality of treatment
      and patient reported outcome (PRO) in orthopaedic surgery.
AB  - BACKGROUND: Previous studies have shown that patients' anxiety and
      dissatisfaction are predictors for increased postoperative pain and reduced
      efficacy of pain treatment. However, it remains to be shown whether patient
      anxiety and concern are predictors for the perceived quality of treatment and
      patient reported outcome (PRO).The aim of this study is to investigate whether
      there is a correlation between preoperative anxiety and concern, and the
      perceived quality of postoperative treatment and outcome. The hypothesis is that
      anxious and concerned patients are less satisfied with treatment and have a
      poorer outcome. METHODS/DESIGN: This study is designed as a prospective follow-up
      study and has the aim of investigating the correlation between patient anxiety
      and concern, patients' perceived quality of treatment and outcome. This
      correlation will be detected using five questionnaires: CMD-SQ (Common Mental
      Disorders Screening Questionnaire), EuroQol 5 Dimensions (EQ-5D), Short form 12
      (SF-12), "What is your evaluation of the patient progress in the Department of
      Orthopaedic Surgery?" (HVOK), Questionnaire for patients who have had hip surgery
      (RCS) and Oxford Hip Score (OHS) or Oxford Shoulder Score (OSS). The patients
      will complete the above mentioned questionnaires preoperatively in the outpatient
      department, and postoperatively just before discharge from the inpatient
      department, and 12 and 52 weeks after the operation. The study includes a
      reliability test of CMD-SQ regarding this specific population and tested by means
      of a Kappa. A total of 500 hip- and shoulder-patients will be included from
      October 2010 till October 2011. DISCUSSION: If a correlation between patient
      anxiety and concern, patients' perceived quality of treatment and patient
      reported outcome is found, it will be recommended to screen all hip- and shoulder
      patients for anxiety and concern preoperatively. Besides, it would be relevant to
      carry out investigations of possible interventions towards anxious and concerned
      patients. TRIAL REGISTRATION: Current Controlled Trials: NCT01205295.

PMID- 22873942
TI  - Proteomics of tear fluid in thyroid-associated orbitopathy.
AB  - BACKGROUND: Proteomics and mass spectrometry are useful tools for peptide
      screening in body fluids. In thyroid-associated orbitopathy (TAO), evidence for
      lacrimal gland involvement with altered composition of tears has been reported.
      Our objective was to detect and evaluate potential changes in the proteomic
      patterns of tear fluid in TAO. METHODS: Tear fluid was collected from 45 patients
      with TAO and 15 healthy controls. Tear proteins were analyzed using surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry, and
      peptides were identified using matrix-assisted laser desorption/ionization time
      of-flight technology. RESULTS: Peptides with molecular weights 3808 Dalton (Da,
      p=0.004), 3734 Da (p=0.034), and 3837 Da (p=0.042), respectively, were
      downregulated in patients with TAO versus controls. They were identified as
      proline-rich protein 4 (PRP4) or as its variant nasopharyngeal carcinoma
      associated PRP4. The peptide 3837 Da correlated positively with the basal
      secretory test (r=0.506, p<0.001) and negatively with the clinical activity score
      (r = -0.334, p<0.05) and age (r=-0.431, p<0.001). Also, a 12,003-Da peptide was
      downregulated (p=0.019) in patients and identified as beta2-microglobulin. This
      peptide decreased in tear fluid with increased clinical severity of TAO
      (p=0.027). In comparison, a 5815-Da peptide was upregulated (p=0.045) and
      identified as lysozyme C. When differentiating between treated and untreated
      patients with TAO, an 11,770-Da peptide (p=0.0072) that was also upregulated was
      identified as cystatin S. CONCLUSIONS: Altered regulation of proinflammatory and
      protective proteins in tears of patients with TAO was demonstrated, reflecting an
      autoimmune- and/or inflammatory-induced dysfunction of the lacrimal gland.

PMID- 22873943
TI  - Usability and preference assessment of a new prefilled insulin pen versus vial
      and syringe in people with diabetes, physicians and nurses.
AB  - OBJECTIVE: This multicenter, crossover study assessed the preference and
      usability of a new prefilled insulin pen, FlexTouch(r) (FT) versus vial and
      syringe (V&S). RESEARCH DESIGN AND METHODS: People with type 1 or type 2 diabetes
      (n = 60), and physicians (n = 30) and nurses (n = 30) with experience of diabetes
      management performed test injections with FT and V&S, and then answered written
      questions on ease of use and preference. MAIN OUTCOME MEASURES: The primary end
      point was preference for FT versus V&S. Secondary end points included perceptions
      of device handling. RESULTS: Significantly more respondents preferred using FT
      (88%) to V&S (5%; p < 0.001; the remainder chose 'no preference'), found FT (91%)
      easier to use than V&S (6%; p < 0.001; the remainder chose 'no preference') and
      would recommend FT (91%) over V&S (3%; p < 0.001; the remainder chose 'no
      preference'). FT received better ratings than V&S for ease of use, holding the
      device stable when injecting, depressing the push-button/plunger and reading the
      dose scale (all p < 0.001). Ratings for confidence in correct insulin delivery
      and controlling blood sugar were also significantly better with FT (both p <
      0.001). CONCLUSIONS: FT was preferred to V&S for insulin delivery in this
      comparative analysis. The features of FT may improve the experience of insulin
      injection compared with V&S for a wide range of people with diabetes.

PMID- 22873944
TI  - Palladium(II)-catalyzed enantio- and diastereoselective synthesis of pyrrolidine
      derivatives.
AB  - A palladium-catalyzed enantio- and diastereoselective synthesis of pyrrolidine
      derivatives is described. Initial intramolecular nucleopalladation of the
      tethered protected amine forms the pyrrolidine moiety and a quinone methide
      intermediate. A second nucleophile adds intermolecularly to afford diverse
      products in high enantio- and diastereoselectivity.

PMID- 22873945
TI  - Life course socio-economic position and quality of life in adulthood: a
      systematic review of life course models.
AB  - BACKGROUND: A relationship between current socio-economic position and subjective
      quality of life has been demonstrated, using wellbeing, life and needs
      satisfaction approaches. Less is known regarding the influence of different life
      course socio-economic trajectories on later quality of life. Several conceptual
      models have been proposed to help explain potential life course effects on
      health, including accumulation, latent, pathway and social mobility models. This
      systematic review aimed to assess whether evidence supported an overall
      relationship between life course socio-economic position and quality of life
      during adulthood and if so, whether there was support for one or more life course
      models. METHODS: A review protocol was developed detailing explicit inclusion and
      exclusion criteria, search terms, data extraction items and quality appraisal
      procedures. Literature searches were performed in 12 electronic databases during
      January 2012 and the references and citations of included articles were checked
      for additional relevant articles. Narrative synthesis was used to analyze
      extracted data and studies were categorized based on the life course model
      analyzed. RESULTS: Twelve studies met the eligibility criteria and used data from
      10 datasets and five countries. Study quality varied and heterogeneity between
      studies was high. Seven studies assessed social mobility models, five assessed
      the latent model, two assessed the pathway model and three tested the
      accumulation model. Evidence indicated an overall relationship, but mixed results
      were found for each life course model. Some evidence was found to support the
      latent model among women, but not men. Social mobility models were supported in
      some studies, but overall evidence suggested little to no effect. Few studies
      addressed accumulation and pathway effects and study heterogeneity limited
      synthesis. CONCLUSIONS: To improve potential for synthesis in this area, future
      research should aim to increase study comparability. Recommendations include
      testing all life course models within individual studies and the use of multiple
      measures of socio-economic position and quality of life. Comparable cross
      national data would be beneficial to enable investigation of between-country
      differences.

PMID- 22873946
TI  - Preparation and characterization and release properties of Eudragit RS based
      ibuprofen pellets prepared by extrusion spheronization: effect of binder type and
      concentration.
AB  - OBJECTIVE: The effects of type and concentration of binding agent on properties
      of Eudragit RS based pellets were studied. MATERIALS AND METHODS: Pellets
      containing ibuprofen (60%), Eudragit RS (30%), Avicel (10%) were prepared by
      extrusion spheronization. PVP K30, PVP K90, HPMC 6cp, HPMC K100LV or HPMC K4M
      were used as binders in concentrations of 2, 4 or 6% based on the total weight of
      formulation. The process efficiency, pellet shape, size distribution, crushing
      strength, elastic modulus and drug release were examined. The effect of curing on
      pellet properties was also investigated. RESULTS: The process of extrusion
      spheronization became difficult with increase in binder viscosity and/or
      concentration. An increase in binder viscosity and/or concentration resulted in
      reduction in the yield of pellets, wider particle size distribution and departure
      from spherical shape especially in the case of HPMC binder. The crushing strength
      and elastic modulus of pellets decreased with increase in PVPs concentration.
      However this was not the case for pellets containing HPMCs. Drug release rate
      increased as the concentration of binder increased. Pellets containing 2%w/w of
      PVP K30 showed the slowest release rate. For those pellets with brittle nature,
      curing changed the behavior of pellet under mechanical test to plastic
      deformation. Yield point and elastic modulus of all formulations decreased after
      curing. Curing decreased the drug release rate. CONCLUSION: Binder type and
      concentration significantly affected the properties of pellets. For production of
      sustained release ibuprofen Eudragit RS based pellets lower viscosity binders
      (PVP K30) with concentrations less than 4%w/w was optimum.

PMID- 22873947
TI  - Resveratrol inhibits postoperative adhesion formation in a rat uterine horn
      adhesion model.
AB  - AIM: Adhesion formation is one of the most important problems occuring after
      pelvic surgery in the majority of women. The aim of this experimental study was
      to investigate the effects of the antioxidant resveratrol (3,5,4'-o
      trihydroxystilbene) on adhesion formation in a rat uterine horn adhesion model.
      MATERIALS AND METHODS: Thirty Wistar-Albino female rats were randomly divided
      into three groups with equal numbers. In Group A, 5.9 mg/kg/day resveratrol was
      applied by the orogastric route for 10 days before and 20 days after surgery. In
      Group B, resveratrol was given only for 20 days after surgery. In the control
      group, no drug was applied before or after surgery. A uterine serosal injury was
      created using a standard technique after laparotomy in all rats. All animals were
      sacrificed 3 weeks after surgery and intrapelvic adhesions determined
      macroscopically and microscopically. RESULTS: Adhesion formation, total adhesion
      score and the severity of adhesions were all significantly lower in both
      resveratrol treatment groups than in the control group (p < 0.05). Notably, the
      severity of adhesions was much less in Group A in which the rats received
      resveratrol before and after surgical operation. CONCLUSIONS: This study suggests
      that 5 +/- 1 mg/kg/day perioperative resveratrol administration is an effective
      strategy for the prevention of postoperative peritoneal adhesion formation after
      pelvic surgery in a rat model.

PMID- 22873948
TI  - Medical student characteristics predictive of intent for rural practice.
AB  - INTRODUCTION: The shortage of physicians in rural areas of the USA has led
      medical schools to focus on recruiting and selecting students who will choose to
      work in non-urban settings. The purpose of this study was to examine the effect
      of student characteristics previously correlated to choosing rural practice (ie
      being older, being male, being raised in a rural community, having a spouse or
      significant other who was raised in a rural community, having a spouse or
      significant other whose parents live in a rural community, having parents with
      high school education or less, and graduating from a smaller college) on
      osteopathic medical students' intent to practice in a rural setting. This study
      also examined the correlation between personality type and intent for rural
      practice using the Myers Briggs Type Indicator (MBTI). Finally, this study
      examined factors that would increase interest in practicing in a rural setting,
      such as financial assistance and students' opinions about physicians who choose
      to practice in rural areas. METHODS: The study participants were students in a
      new osteopathic medical school with an enrollment of 225. Cross-sectional survey
      data were collected on background characteristics and intent for rural practice.
      Retrospective data were collected from MBTI assessments previously completed as
      part of routine career planning educational sessions. Data were analyzed using
      descriptive statistics such as frequencies, percentages and inferential
      statistics such as chi2 and logistic regression. RESULTS: A total of 141 students
      participated, a 63% response rate. Factors associated with intent to practice
      rural medicine included being raised in a rural area for more than half of one's
      life (p<0.05) and having a spouse or significant other who had lived in a rural
      area (p<0.05). Age, sex, race, and size of undergraduate college were not
      associated with intent to practice rural medicine. Students categorized as
      Extraverted based on the MBTI were more likely to have intent for rural practice
      even when other factors were controlled. Students reported that financial
      incentives and wage guarantees may increase interest in rural practice.
      CONCLUSION: The results of this study support past research showing that medical
      students with a rural background and with spouses or significant others having a
      rural background are more likely to have intent for rural practice. This study
      also found that students' personality types may be correlated with intent to
      practice in a rural area. In order to provide physicians who will serve the
      population living in rural areas of the USA, it is imperative that medical
      schools select students who are most likely to practice in a non-urban setting.
      Financial incentives are important to students, suggesting that programs such as
      loan forgiveness may be useful in recruiting students to rural practice. Medical
      students may benefit from career counseling utilizing the MBTI to facilitate an
      understanding of personality type and how it may impact their preference for
      rural practice.

PMID- 22873949
TI  - Tuning the transmittance of colloidal solution by changing the orientation of Ag
      nanoplates in ferrofluid.
AB  - Ag nanoplates and Fe(3)O(4) nanoparticle-based ferrofluids were utilized to
      fabricate a magnetic field controlled optic switch. The changing of light
      transmittance (LT) is caused by the rotation of Ag nanoplates, whose long axis
      always follows the orientation of external magnetic field to minimize the
      potential energy. The sensitivity of switching was optimized by choosing Ag
      nanoplates with appropriate size and concentration. The switching of transmission
      is proved to be fast and fully reversible. This phenomenon not only indicates an
      effective method to adjust the propagation of optical signals, but also reveals
      the possibility and great potential to develop magnetic controlled functional
      devices.

PMID- 22873950
TI  - Analysis of plant-derived miRNAs in animal small RNA datasets.
AB  - BACKGROUND: Plants contain significant quantities of small RNAs (sRNAs) derived
      from various sRNA biogenesis pathways. Many of these sRNAs play regulatory roles
      in plants. Previous analysis revealed that numerous sRNAs in corn, rice and
      soybean seeds have high sequence similarity to animal genes. However, exogenous
      RNA is considered to be unstable within the gastrointestinal tract of many
      animals, thus limiting potential for any adverse effects from consumption of
      dietary RNA. A recent paper reported that putative plant miRNAs were detected in
      animal plasma and serum, presumably acquired through ingestion, and may have a
      functional impact in the consuming organisms. RESULTS: To address the question of
      how common this phenomenon could be, we searched for plant miRNAs sequences in
      public sRNA datasets from various tissues of mammals, chicken and insects. Our
      analyses revealed that plant miRNAs were present in the animal sRNA datasets, and
      significantly miR168 was extremely over-represented. Furthermore, all or nearly
      all (>96%) miR168 sequences were monocot derived for most datasets, including
      datasets for two insects reared on dicot plants in their respective experiments.
      To investigate if plant-derived miRNAs, including miR168, could accumulate and
      move systemically in insects, we conducted insect feeding studies for three
      insects including corn rootworm, which has been shown to be responsive to plant
      produced long double-stranded RNAs. CONCLUSIONS: Our analyses suggest that the
      observed plant miRNAs in animal sRNA datasets can originate in the process of
      sequencing, and that accumulation of plant miRNAs via dietary exposure is not
      universal in animals.

PMID- 22873951
TI  - Metabolomic signatures in guinea pigs infected with epidemic-associated W-Beijing
      strains of Mycobacterium tuberculosis.
AB  - With the understanding that the laboratory propagated strain of Mycobacterium
      tuberculosis H37Rv is of modest virulence and is drug susceptible, in the present
      study, we performed a nuclear magnetic resonance-based metabolomic analysis of
      lung tissues and serum obtained from guinea pigs infected by low dose aerosol
      exposure to clinical isolates of Mycobacterium tuberculosis. High Resolution
      Magic Angle Spinning NMR coupled with multivariate statistical analysis of 159
      lung tissues obtained from multiple locations of age-matched naive and 30 and 60
      days of infected guinea pig lungs revealed a wide dispersal of metabolic
      patterns, but within these, distinct clusters of signatures could be seen that
      differentiated between naive control and infected animals. Several metabolites
      were identified that changed in concert with the progression of each infection.
      Major metabolites that could be interpreted as indicating host glutaminolysis
      were consistent with activated host immune cells encountering increasingly
      hypoxic conditions in the necrotic lung lesions. Moreover, glutathione levels
      were constantly elevated, probably in response to oxygen radical production in
      these lesions. Additional distinct signatures were also seen in infected serum,
      with altered levels of several metabolites. Multivariate statistical analysis
      clearly differentiated the infected from the uninfected sera; in addition,
      Receiver Operator Characteristic curve generated with principal component 1
      scores showed an area under the curve of 0.908. These data raise optimism that
      discrete metabolomic signatures can be defined that can predict the progression
      of the tuberculosis disease process, and form the basis of an innovative and
      rapid diagnostic process.

PMID- 22873952
TI  - Rotavirus genotypes in children in the Basque Country (North of Spain): rapid and
      intense emergence of the G12[P8] genotype.
AB  - Between July 2009 and June 2011, rotavirus was detected in 507 of 4597 episodes
      of acute gastroenteritis in children aged <3 years in Gipuzkoa (Basque Country,
      Spain), of which the G-type was determined in 458 (90.3%). During the annual
      seasonal epidemic of 2010-2011, the unusual G-type 12 was predominant, causing
      65% (145/223) of cases of rotavirus gastroenteritis. All the G12 strains were
      clustered in lineage III and were preferentially associated with P-type 8. This
      epidemic was characterized by broad geographical distribution (rural and urban)
      and, over 7 months, affected both infants and children, the most frequently
      affected being children between 4 and 24 months. Of children with rotavirus G12,
      16% required hospital admission, the admission rate in children aged <2 years
      being 20.7 cases/10 000 children. The sudden emergence and predominance of G12
      rotaviruses documented in this winter outbreak suggest that they may soon become
      a major human rotavirus genotype.

PMID- 22874003
TI  - Best-bet integrated strategies for containing drug-resistant trypanosomes in
      cattle.
AB  - BACKGROUND: African animal trypanosomosis is a major constraint to the rearing of
      productive livestock in the sub-humid Sudan-Sahel zone of West Africa where
      cotton is grown. Trypanosomosis is mainly controlled using trypanocidal drugs,
      but the effective use of drugs is threatened by the development of widespread
      resistance. This study tested integrated best-bet strategies for containment and/
      or reversal of trypanocide resistance in villages in south-east Mali where
      resistance has been reported. METHODS: Four sentinel villages each from an
      intervention area (along the road from Mali to Burkina Faso) and a control area
      (along the road from Mali to Cote d'Ivoire) were selected for the study. Tsetse
      control was based on deltamethrin-treated stationary attractive devices and
      targeted cattle spraying between March 2008 and November 2009. Trypanosome
      positive cattle were selectively treated with 3.5 mg/kg diminazene aceturate.
      Strategic helminth control using 10 mg/kg albendazole was also undertaken. During
      the intervention, tsetse densities along drainage lines, trypanosome infections
      and faecal egg counts in risk cattle (3 to 12 months of age) were monitored.
      RESULTS: Catch reductions of 66.5 % in Glossina palpalis gambiensis and 90 % in
      G. tachinoides were observed in the intervention area. Trypanosome prevalence was
      significantly (p < 0.05) lower in the intervention area (2.3 %; 1.3-3.6 %)
      compared to the control area (17.3 %; 14.8-20.1 %). Albendazole treatment
      resulted in a faecal egg count reduction of 55.6 % and reduced trypanosome
      infection risk (2.9 times lower than in the placebo group) although not
      significantly (p > 0.05). Further studies are required before confirming the
      existence of albendazole resistant strongyles in the study area. CONCLUSION:
      Integration of best-bet strategies in areas of multiple drug-resistance is
      expected to reduce trypanosome infection risk thus contributing to containment of
      trypanocidal drug resistance. Integrated best-bet strategies could therefore be
      considered a viable trypanosomosis control option especially in areas where
      multiple drug-resistance has been reported.

PMID- 22874004
TI  - Does a text messaging intervention improve knowledge, attitudes and practice
      regarding iodine deficiency and iodized salt consumption?
AB  - OBJECTIVE: To determine the effectiveness of implementation of a prevention
      programme via mobile phone text messaging in enhancing knowledge, attitudes and
      practice concerning iodine deficiency and iodized salt consumption. DESIGN: In a
      randomized controlled trial, participants were subjected to a brief tele
      educational support regarding iodine deficiency and the importance of iodized
      salt consumption. The intervention group received daily text messages via mobile
      phone for 6 weeks. Knowledge, attitude and practice scores, urinary iodine
      concentration and salt iodine content were assessed at baseline and 8 weeks after
      the intervention. SETTING: Participants were recruited from health-care centres
      in Tehran, the capital city of Iran. SUBJECTS: For the present study 205 females
      aged >=18 years were randomly assigned to the intervention (n 95) and control (n
      110) groups. RESULTS: A significant difference was found in median knowledge
      scores between the intervention and control groups at follow-up (P = 0.004).
      There was also a significant difference in median attitude scores between the
      intervention and control groups (P = 0.02). The intervention group did not differ
      significantly in median practice score, urinary iodine concentration and salt
      iodine content from the control group. CONCLUSIONS: Text messaging interventions
      are effective in improving individuals' knowledge and attitudes regarding
      preventive health-care topics.

PMID- 22874005
TI  - Structure refinement and two-center luminescence of Ca3La3(BO3)5:Ce3+ under VUV
      UV excitation.
AB  - A series of Ca(3)La(3(1-x))Ce(3x)(BO(3))(5) phosphors were prepared by a high
      temperature solid-state reaction technique. Rietveld refinement was performed
      using the powder X-ray diffraction (XRD) data, which shows occupation of Ce(3+)
      on both Ca(2+) and La(3+) sites with a preferred location on the La(3+) site over
      the Ca(2+) site. The prepared samples contain minor second phase LaBO(3) with
      contents of ~0.64-3.27 wt % from the Rietveld analysis. LaBO(3):1%Ce(3+) was
      prepared as a single phase material and its excitation and emission bands were
      determined for identifying the influence of impurity LaBO(3):Ce(3+) luminescence
      on the spectra of the Ca(3)La(3(1-x))Ce(3x)(BO(3))(5) samples. The luminescence
      properties of Ca(3)La(3(1-x))Ce(3x)(BO(3))(5) samples under vacuum ultraviolet
      (VUV) and UV excitation were investigated, which exhibited two-center
      luminescence of Ce(3+), assigned to the Ce(1)(3+) center in the La(3+) site and
      Ce(2)(3+) center in the Ca(2+) site, taking into account the spectroscopic
      properties and the Rietveld refinement results. The influences of the doping
      concentration and the excitation wavelength on the luminescence of Ce(3+) in
      Ca(3)La(3(1-x))Ce(3x)(BO(3))(5) are discussed together with the decay
      characteristics.

PMID- 22874006
TI  - Evidence of microglial activation in autism and its possible role in brain
      underconnectivity.
AB  - Evidence indicates that children with autism spectrum disorder (ASD) suffer from
      an ongoing neuroinflammatory process in different regions of the brain involving
      microglial activation. When microglia remain activated for an extended period,
      the production of mediators is sustained longer than usual and this increase in
      mediators contributes to loss of synaptic connections and neuronal cell death.
      Microglial activation can then result in a loss of connections or
      underconnectivity. Underconnectivity is reported in many studies in autism. One
      way to control neuroinflammation is to reduce or inhibit microglial activation.
      It is plausible that by reducing brain inflammation and microglial activation,
      the neurodestructive effects of chronic inflammation could be reduced and allow
      for improved developmental outcomes. Future studies that examine treatments that
      may reduce microglial activation and neuroinflammation, and ultimately help to
      mitigate symptoms in ASD, are warranted.

PMID- 22874007
TI  - Genetics of population exchange along the historical Portuguese-Spanish border.
AB  - The present analysis compares the distribution of surnames by means of spatial
      autocorrelation analysis in the Spain-Portugal border region. The Spanish
      National Institute of Statistics provides a database of surnames of residents in
      the western Spanish provinces of Zamora, Salamanca, Caceres, Badajoz and Huelva.
      The Spanish and Portuguese patterns of surname distribution were established
      according to various geographic axes. The results obtained show a low diversity
      of surnames in this region - especially in the centre - which can be explained by
      the absence of any major geographic barriers, with the exception of the mountain
      ranges between hydrographic basins, and by the presence of traditional roads that
      have existed since Roman times. The latter have resulted in a constant migratory
      flow over short-median distances, which, as can be deduced from the surnames,
      fits two north/south territorial axes running parallel to the border between
      Spain and Portugal. The distribution patterns of Portuguese and Spanish surnames
      differ with regard to their frequencies in the five provinces studied, which can
      be attributed to their respective historical, economic and social conditions. It
      is concluded that the border delimiting these two countries has affected the
      migratory flow, thereby conditioning the demographic and genetic structure of the
      western Spanish regions.

PMID- 22874008
TI  - The role of number of meals, coffee intake, salt and type of cookware on
      colorectal cancer development in the context of the Mediterranean diet.
AB  - OBJECTIVE: To investigate the association between dietary behaviours and
      colorectal cancer (CRC) in the context of the Mediterranean diet. DESIGN: Case
      control study. SETTING: All patients (cases) were recruited from Saint Savvas
      Cancer Hospital and Alexandra General Hospital in Athens, Greece. Controls were
      voluntarily selected from the general population and matched to cases by age
      group (+/-10 years) and sex. SUBJECTS: Two hundred and fifty cases with newly
      diagnosed CRC (mean age 63 (sd 12) years, 59.6 % males) and 250 controls matched
      on age and sex were studied. A standardized questionnaire assessing
      sociodemographic, clinical, lifestyle, dietary characteristics and nutritional
      behaviours was applied. Multiple logistic regression analysis was used to
      evaluate the aforementioned factors in addition to the MedDietScore (an index
      that evaluates adherence to the Mediterranean diet) on CRC development. RESULTS:
      The higher the daily number of meals, the lower the likelihood of having CRC (OR
      = 0.74, 95 % CI 0.61, 0.89); coffee drinking was associated with higher
      likelihood of having CRC (OR = 3.27, 95 % CI 1.09, 9.8); the use of non-stick
      cookware was positively associated with CRC (OR = 1.57, 95 % CI 1.02, 2.4).
      However, these associations slightly lost their significance when adherence to
      the Mediterranean diet was taken into account. Moreover, a 1/75 increase in the
      modified-MedDietScore plus the aforementioned nutritional behaviours was
      associated with 13 % lower odds (95 % CI 0.83, 0.91, P < 0.001) of having CRC.
      CONCLUSIONS: Nutritional behaviours in addition to dietary habits should be taken
      into account in detecting individuals prone to the development of CRC.

PMID- 22874009
TI  - Electrophilic adduction of ubiquitin activating enzyme E1 by N,N
      diethyldithiocarbamate inhibits ubiquitin activation and is accompanied by
      striatal injury in the rat.
AB  - Previous studies have shown ubiquitin activating enzyme E1 to be sensitive to
      adduction through both Michael addition and SN(2) chemistry in vitro. E1 presents
      a biologically important putative protein target for adduction due to its role in
      initiating ubiquitin based protein processing and the involvement of impaired
      ubiquitin protein processing in two types of familial Parkinson's disease. We
      tested whether E1 is susceptible to xenobiotic-mediated electrophilic adduction
      in vivo and explored the potential contribution of E1 adduction to
      neurodegenerative events in an animal model. N,N-Diethyldithiocarbamate (DEDC)
      was administered to rats using a protocol that produces covalent cysteine
      modifications in vivo, and brain E1 protein adducts were characterized and mapped
      using shotgun LC-MS/MS. E1 activity, global and specific protein expression, and
      protein carbonyls were used to characterize cellular responses and injury in
      whole brain and dorsal striatal samples. The data demonstrate that DEDC treatment
      produced S-(ethylaminocarbonyl) adducts on Cys234 and Cys179 residues of E1 and
      decreased the levels of activated E1 and total ubiquitinated proteins. Proteomic
      analysis of whole brain samples identified expression changes for proteins
      involved in myelin structure, antioxidant response, and catechol metabolism,
      systems often disrupted in neurodegenerative disease. Our studies also delineated
      localized injury within the striatum as indicated by decreased levels of tyrosine
      hydroxylase, elevated protein carbonyl content, increased antioxidant enzyme and
      alpha-synuclein expression, and enhanced phosphorylation of tau and tyrosine
      hydroxylase. These data are consistent with E1 having similar susceptibility to
      adduction in vivo as previously reported in vitro and support further
      investigation into environmental agent adduction of E1 as a potential
      contributing factor to neurodegenerative disease. Additionally, this study
      supports the predictive value of in vitro screens for identifying sensitive
      protein targets that can be used to guide subsequent in vivo experiments.

PMID- 22874011
TI  - Qi, acupuncture, and the fascia: a reconsideration of the fundamental principles
      of acupuncture.
AB  - Qi is a complex philosophical principle that may be applied to everything that
      exists. The qi principle, as has been commonly applied to acupuncture, is
      inconsistent with its application in other areas. This article considers the
      acupuncture concept of qi in light of recent research, particularly studies
      expanding the role of the fascia in human health. Qi is discussed in the context
      of philosophical, historical, and cross-cultural perspectives. The discussion
      includes the fascia acupuncture hypothesis, which suggests that fascial planes
      are the channels and the stimulation of the fascia results in activity of the
      tissue capable of affecting every aspect of physiology. Based on structural and
      functional parallels between the channel system and the fascia, such activity is
      hypothesized to be the qi of the channels, providing consistency to the
      application of the qi principle. Both acupuncture and "sham" acupuncture
      stimulate the fascia, perhaps contributing to the results of meta-analyses of
      clinical acupuncture research. Implications for future research and acupuncture
      education are discussed.

PMID- 22874010
TI  - The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis.
AB  - BACKGROUND: Cystic Fibrosis (CF) is a monogenic disease with complex expression
      because of the action of genetic and environmental factors. We investigated
      whether the ACE gene D/I polymorphism is associated with severity of CF. METHODS:
      A cross-sectional study was performed, from 2009 to 2011, at University of
      Campinas - UNICAMP. We analyzed 180 patients for the most frequent mutations in
      the CFTR gene, presence of the ACE gene D/I polymorphism and clinical
      characteristics of CF. RESULTS: There was an association of the D/D genotype with
      early initiation of clinical manifestations (OR: 1.519, CI: 1.074 to 2.146),
      bacterium Burkholderia cepacia colonization (OR: 3.309, CI: 1.476 to 6.256) and
      Bhalla score (BS) (p = 0.015). The association was observed in subgroups of
      patients which were defined by their CFTR mutation genotype (all patients;
      subgroup I: no mutation detected; subgroup II: one CFTR allele identified to
      mutation class I, II or III; subgroup III: both CFTR alleles identified to
      mutation class I, II and/or III). CONCLUSION: An association between the D allele
      in the ACE gene and the severity of CF was found in our study.

PMID- 22874012
TI  - Integral quantification accuracy estimation for reporter ion-based quantitative
      proteomics (iQuARI).
AB  - With the increasing popularity of comparative studies of complex proteomes,
      reporter ion-based quantification methods such as iTRAQ and TMT have become
      commonplace in biological studies. Their appeal derives from simple multiplexing
      and quantification of several samples at reasonable cost. This advantage yet
      comes with a known shortcoming: precursors of different species can interfere,
      thus reducing the quantification accuracy. Recently, two methods were brought to
      the community alleviating the amount of interference via novel experimental
      design. Before considering setting up a new workflow, tuning the system,
      optimizing identification and quantification rates, etc. one legitimately asks:
      is it really worth the effort, time and money? The question is actually not easy
      to answer since the interference is heavily sample and system dependent.
      Moreover, there was to date no method allowing the inline estimation of error
      rates for reporter quantification. We therefore introduce a method called iQuARI
      to compute false discovery rates for reporter ion based quantification
      experiments as easily as Target/Decoy FDR for identification. With it, the
      scientist can accurately estimate the amount of interference in his sample on his
      system and eventually consider removing shadows subsequently, a task for which
      reporter ion quantification might not be the solution of choice.

PMID- 22874013
TI  - Feasibility study for the detection of Trichinella spiralis in a murine model
      using mid-Fourier transform infrared spectroscopy (MID-FTIR) with attenuated
      total reflectance (ATR) and soft independent modelling of class analogies
      (SIMCA).
AB  - Fourier transform infrared (FTIR) spectroscopy with attenuated total reflectance
      (ATR) and soft independent modelling by class analogies (SIMCA) was used to
      assess the feasibility of detecting Trichinella spiralis in a murine model. The
      selected FTIR wavenumber range was 1700-900 cm(-1) and the first derivative of
      the spectra was subjected to SIMCA analysis. The SIMCA model developed for rat
      meat spiked with T. spiralis larvae was successfully apply to classify non
      infected from infected rat meat with a limit of detection of 3 larvae/10 g rat
      meat and no false positives with 99% confidence limit. To avoid false positives
      arising from the presence of other parasites, another chemometric model was
      developed to demonstrate the capacity of the model to discriminate between
      Ascaris suum, Taenia solium and T. spiralis. Results confirmed that this method
      could correctly distinguish these parasites. Additional studies are needed to
      prove the effectiveness of this technique for other types of muscle meats,
      including those relevant to human consumption.

PMID- 22874064
TI  - Increased cleavage rate of human nuclear transfer embryos after 5-aza-2'
      deoxycytidine treatment.
AB  - As an abundant source that involves fewer ethical considerations, human
      abnormally fertilized zygotes are superior to oocytes as therapeutic cloning
      recipients of nuclear transfer. However, more effective manipulation conditions
      should be developed for somatic cell nuclear transfer (SCNT) studies using human
      abnormally fertilized zygotes as recipients. The present study found that the use
      of cytochalasin B was not necessary for, and even harmful to, the enucleation of
      human zygotes. This study also decreased the DNA methylation levels in
      reconstructed embryos using a DNA methyltransferase inhibitor, 5-aza-2'
      deoxycytidine (5-aza-dC), in an attempt to correct the abnormalities in DNA
      methylation that might play an important role in the failure of embryo
      development. After 5-aza-dC treatment and nuclear transfer (NT-Aza group), 32.7%
      of reconstructed embryos developed to the 8-cell stage, which is a much higher
      percentage than that of the nuclear transfer only (NT) group (11.1%). The DNA
      methylation level in the NT-Aza group was significantly lower than that of the NT
      group, as determined by 5-methylcytosine immunodetection. Based on the present
      results, this study recommends performing the enucleation procedure without
      cytochalasin B treatment and using 5-aza-dC in the culture of reconstructed
      embryos in human SCNT studies.

PMID- 22874065
TI  - Regulation of dual oxidase expression and H2O2 production by thyroglobulin.
AB  - BACKGROUND: Thyroglobulin (Tg) is a macromolecular precursor in thyroid hormone
      synthesis to which iodine is stably bound. Tg, which is stored in the follicular
      space, is also a potent negative feedback regulator of follicular function, and
      this is achieved by suppressing mRNA levels of thyroid-specific genes such as the
      sodium/iodide symporter (Slc5a5), Tg, and thyroid peroxidase. Dual oxidase 1
      (DUOX1) and DUOX2, originally identified in the thyroid, are nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidases that are necessary to produce the H2O2
      required for thyroid hormone biosynthesis. Since follicular Tg regulates the
      expression of genes that are essential for thyroid hormone synthesis, we
      hypothesized that Tg might also regulate DUOX expression and H2O2 production.
      METHODS: Rat thyroid FRTL-5 cells were treated with Tg, and the mRNA expression
      of Duox1 and Duox2 and their corresponding maturation factors Duoxa1 and Duoxa2
      were evaluated by DNA microarray and real-time PCR. Duox2 promoter activity was
      examined by luciferase reporter gene assay. Protein levels of DUOX2 were also
      examined by Western blot analysis. Intracellular H2O2 generation was quantified
      by a fluorescent dye, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein
      diacetate, and acetyl ester (CM-H2DCFDA). RESULTS: mRNA levels of Duox2 and its
      activation factor Duoxa2 (but not Duox1 or Duoxa1) were significantly suppressed
      by Tg in a dose-dependent manner and a time-dependent fashion in rat thyroid FRTL
      5 cells. DUOX2 promoter activity was significantly suppressed by Tg in a dose
      dependent manner. Protein levels of DUOX2 and H2O2 generation in cells were also
      reduced by Tg treatment. CONCLUSIONS: We show that physiological concentrations
      of Tg suppressed the expression and function of DUOX2 in thyroid cells. These
      results suggest that Tg is a strong suppressor of the expression and the activity
      of DUOX2/DUOXA2, thereby regulating iodide organification and hormone synthesis
      in the thyroid. The evidence supports a reported model in which accumulated Tg in
      thyroid follicles plays important roles in autoregulating the function of
      individual follicles, which produces the basis of follicular heterogeneity.

PMID- 22874066
TI  - Quadricuspid aortic valve with ruptured sinus of Valsalva.
AB  - We present a case of a 24-year-old woman who was diagnosed with quadricuspid
      aortic valve with ruptured sinus of Valsalva. Quadricuspid aortic valve is a rare
      congenital cardiac anomaly. The recognition of quadricuspid aortic valve has
      clinical significance as it causes aortic valve dysfunction, and is often
      associated with other congenital cardiac abnormalities. We showed the important
      role of multimodality imaging in diagnosing a quadricuspid aortic valve
      associated with ruptured sinus of Valsalva.

PMID- 22874067
TI  - Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in
      risk stratification of critically ill febrile patients in Emergency Department
      (ED). A comparison with APACHE II score.
AB  - BACKGROUND: The aim of our study was to evaluate the prognostic value of MR
      proADM and PCT levels in febrile patients in the ED in comparison with a disease
      severity index score, the APACHE II score. We also evaluated the ability of MR
      proADM and PCT to predict hospitalization. METHODS: This was an observational,
      multicentric study. We enrolled 128 patients referred to the ED with high fever
      and a suspicion of severe infection such as sepsis, lower respiratory tract
      infections, urinary tract infections, gastrointestinal infections, soft tissue
      infections, central nervous system infections, or osteomyelitis. The APACHE II
      score was calculated for each patient. RESULTS: MR-proADM median values in
      controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001),
      while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P <
      0.0001). In all patients there was a statistically significant stepwise increase
      in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT
      levels were significantly increased in accordance with the Apache II quartiles (P
      < 0.0001 and P = 0.0012 respectively).In the respiratory infections, urinary
      infections, and sepsis-septic shock groups we found a correlation between the
      Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We
      evaluated the ability of MR-proADM and PCT to predict hospitalization in patients
      admitted to our emergency departments complaining of fever. MR-proADM alone had
      an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and
      MR-proADM instead showed an AUC of 0.79. CONCLUSIONS: The present study
      highlights the way in which MR-proADM and PCT may be helpful to the febrile
      patient's care in the ED. Our data support the prognostic role of MR-proADM and
      PCT in that setting, as demonstrated by the correlation with the APACHE II score.
      The combined use of the two biomarkers can predict a subsequent hospitalization
      of febrile patients. The rational use of these two molecules could lead to
      several advantages, such as faster diagnosis, more accurate risk stratification,
      and optimization of the treatment, with consequent benefit to the patient and
      considerably reduced costs.

PMID- 22874068
TI  - Human cytomegalovirus infection of THP-1 derived macrophages reveals strain
      specific regulation of actin dynamics.
AB  - Human cytomegalovirus (HCMV) remains latent in cells of the myeloid lineage after
      primary infection. The THP-1 monocytic cell line is conditionally permissive for
      infection and has been used primarily to study the process of HCMV reactivation
      when the cells are induced to differentiate. In the present report, we
      characterized lytic infection in THP-1 derived macrophages using two strains of
      HCMV, Towne and BAC-derived TR. Our findings indicate that these cells express
      viral genes of all three kinetic classes and produce extracellular virus, but
      that there is a delay in these processes relative to productively infected
      fibroblasts. Importantly, our studies in THP-1 derived macrophages revealed
      strain-specific differences in pp65 trafficking and actin dynamics. Based on
      these observations, our studies indicate that differentiated THP-1 cells can
      serve as a valuable model for lytic infection.

PMID- 22874069
TI  - The role of the alternative coreceptor GPR15 in SIV tropism for human cells.
AB  - Many SIV isolates can employ the orphan receptor GPR15 as coreceptor for
      efficient entry into transfected cell lines, but the role of endogenously
      expressed GPR15 in SIV cell tropism is largely unclear. Here, we show that
      several human B and T cell lines express GPR15 on the cell surface, including the
      T/B cell hybrid cell line CEMx174, and that GPR15 expression is essential for SIV
      infection of CEMx174 cells. In addition, GPR15 expression was detected on subsets
      of primary human CD4(+), CD8(+) and CD19(+) peripheral blood mononuclear cells
      (PBMCs), respectively. However, GPR15(+) PBMCs were not efficiently infected by
      HIV and SIV, including cells from individuals homozygous for the defective
      Delta32 ccr5 allele. These results suggest that GPR15 is coexpressed with CD4 on
      PBMCs but that infection of CD4(+), GPR15(+) cells is not responsible for the
      well documented ability of SIV to infect CCR5(-) blood cells.

PMID- 22874070
TI  - The statistical signature of morphosyntax: a study of Hungarian and Italian
      infant-directed speech.
AB  - Does statistical learning (Saffran, Aslin, & Newport, 1996) offer a universal
      segmentation strategy for young language learners? Previous studies on large
      corpora of English and structurally similar languages have shown that statistical
      segmentation can be an effective strategy. However, many of the world's languages
      have richer morphological systems, with sometimes several affixes attached to a
      stem (e.g. Hungarian: iskolainkban: iskola-i-nk-ban school.pl.poss1pl.inessive
      'in our schools'). In these languages, word boundaries and morpheme boundaries do
      not coincide. Does the internal structure of words affect segmentation? What word
      forms does segmentation yield in morphologically rich languages: complex word
      forms or separate stems and affixes? The present paper answers these questions by
      exploring different segmentation algorithms in infant-directed speech corpora
      from two typologically and structurally different languages, Hungarian and
      Italian. The results suggest that the morphological and syntactic type of a
      language has an impact on statistical segmentation, with different strategies
      working best in different languages. Specifically, the direction of segmentation
      seems to be sensitive to the affixation order of a language. Thus, backward
      probabilities are more effective in Hungarian, a heavily suffixing language,
      whereas forward probabilities are more informative in Italian, which has fewer
      suffixes and a large number of phrase-initial function words. The consequences of
      these findings for potential segmentation and word learning strategies are
      discussed.

PMID- 22874071
TI  - A memory advantage for untrustworthy faces.
AB  - Inferences of others' social traits from their faces can influence how we think
      and behave towards them, but little is known about how perceptions of people's
      traits may affect downstream cognitions, such as memory. Here we explored the
      relationship between targets' perceived social traits and how well they were
      remembered following a single brief perception, focusing primarily on inferences
      of trustworthiness. In Study 1, participants encoded high-consensus trustworthy
      and untrustworthy faces, showing significantly better memory for the latter
      group. Study 2 compared memory for faces rated high and low on a series of traits
      (dominance, facial maturity, likeability, and trustworthiness), and found that
      untrustworthy and unlikeable faces were remembered best, with no differences for
      the other traits. Finally, Study 3 compared information about trustworthiness
      from facial appearance and from behavioral descriptions. Untrustworthy targets
      were remembered better than trustworthy targets both from behavior and faces,
      though the effects were significantly stronger for the latter. Faces perceived as
      untrustworthy therefore appear to be remembered better than faces perceived as
      trustworthy. Consistent with ecological theories of perception, cues to
      trustworthiness from facial appearance may thus guide who is remembered and who
      is forgotten at first impression.

PMID- 22874073
TI  - Bordetella holmesii in children suspected of pertussis in Argentina.
AB  - We describe nine patients (eight aged <1 year) clinically diagnosed with
      pertussis yet laboratory-confirmed with Bordetella holmesii infections, a human
      pathogen normally isolated from blood. Most patients reported cough and cold
      symptoms. No death was reported. We report B. holmesii isolation in infants with
      respiratory symptoms in Argentina.

PMID- 22874072
TI  - Disordered follicle development.
AB  - Alterations of ovarian follicle morphology and function have been well documented
      in women with PCOS. These include increased numbers of growing preantral
      follicles, failure of follicle growth beyond the mid-antral stage, evidence of
      granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities
      include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically
      linked to ovarian hyperstimulation during ovulation induction. In addition, there
      is likely a primary theca cell defect that accounts for the majority of excess
      androgen production in this disorder. The precise mechanisms responsible for
      altered follicle function are not completely clear. However, several factors
      appear to influence normal advancement of follicle development as well as impair
      ovarian steroidogenesis. These include intra- as well as extraovarian influences
      that distort normal ovarian growth and disrupt steroid production by follicle
      cells.

PMID- 22874074
TI  - Utility of the waist-to-height ratio as an instrument to measure parental
      perception of body weight in children and its use in a population-based survey of
      children.
AB  - OBJECTIVE: To investigate which anthropometric measure of overweight status, BMI
      or waist-to-height ratio (WHtR), is most closely associated with parents'
      perception of their child's overweight status. DESIGN: The sensitivity and
      specificity of parental perception against child-specific BMI and WHtR
      definitions of overweight were tested. SETTING: Primary schools in Queensland,
      Australia. SUBJECTS: Boys and girls aged 9.00-11.99 years (n 1431). RESULTS: Of
      the 138 boys and 202 girls who were classified as overweight according to BMI,
      only 27.5 % (boys) and 22.7 % (girls) were also perceived as overweight by their
      parents. Using WHtR, 206 boys and 333 girls were classified as overweight, of
      whom only 21.9 % and 13.8 %, respectively, were perceived as overweight.
      Perception of overweight was underestimated in approximately 15 % of boys and 21
      % of girls when compared with BMI. Underestimation was higher when compared with
      WHtR: 25 % (boys) and 39 % (girls). Overweight prevalence was significantly lower
      according to perception than according to BMI or WHtR. Mother's education level
      was significantly associated with accurate perception of overweight status (P <
      0.001). CONCLUSIONS: The sensitivity of parental perception of child overweight
      was higher when BMI was used. However, emphasis needs to be placed on using WHtR
      as an actual measure of overweight because high central adiposity is associated
      with increased risk of CVD. The combined use of WHtR, body-shape images rather
      than word responses regarding perception and public health messages that educate
      parents and children about body shape and associated health risks may be the best
      combination in improving parents' perception of their child's overweight status.

PMID- 22874075
TI  - Influence of the different sodium chloride concentrations on microbiological and
      physico-chemical characteristics of mozzarella cheese.
AB  - In this work the effects of addition of different amounts of sodium chloride,
      during cheese making, on shelf life of mozzarella cheese were evaluated. The
      mozzarella cheese quality decay was assessed during storage at 9  degrees C by
      monitoring microbiological, sensory and physico-chemical changes in the product.
      Results showed that Pseudomonas spp. growth was responsible for cheese
      unacceptability, whereas the sensory quality did not limit cheese shelf life. In
      particular, the highest shelf life values were obtained for mozzarella without
      salt and with the lowest salt concentration (0.23 g NaCl), and amounted to about
      5 and 4 d, respectively. On the contrary, high salt concentrations affected
      product shelf life, probably as a consequence of progressive solubilisation of
      cheese casein, due to the phenomenon of 'salting in'.

PMID- 22874077
TI  - Catalogue of failures at Manchester hospital contributed to disabled girl's
      death.

PMID- 22874078
TI  - The index of microcirculatory resistance predicts myocardial infarction related
      to percutaneous coronary intervention.
AB  - BACKGROUND: Periprocedural myocardial infarction (MI) occurs in a significant
      proportion of patients undergoing percutaneous coronary intervention (PCI) and
      portends poor outcomes. Currently, no clinically applicable method predicts
      periprocedural MI in the cardiac catheterization laboratory before it occurs. We
      hypothesized that impaired baseline coronary microcirculatory reserve, which
      reduces the ability to tolerate ischemic insults, is a risk for periprocedural MI
      and that the index of microcirculatory resistance (IMR) measured during PCI can
      predict occurrence of periprocedural MI. METHODS AND RESULTS: Consecutive
      patients undergoing elective PCI of a single lesion in the left anterior
      descending coronary artery were recruited. A pressure-temperature sensor wire was
      used to measure IMR before PCI. Of the 50 patients studied, 10 had periprocedural
      MI. From binary logistic regression analyses of all clinical, procedural, and
      physiological parameters, univariable predictors of periprocedural MI were pre
      PCI IMR (P=0.003) and the number of stents used (P=0.039). Pre-PCI IMR was the
      only independent predictor in bivariable regression analyses performed by
      adjusting for each available covariate one at a time (all P<=0.02). Pre-PCI IMR
      >=27 U had 80.0% sensitivity and 85.0% specificity for predicting periprocedural
      MI (C statistic, 0.80; P=0.003). Pre-PCI IMR >=27 U was independently associated
      with a 23-fold risk of developing periprocedural MI (odds ratio, 22.7; 95% CI,
      3.8-133.9). CONCLUSIONS: These data suggest that the status of the coronary
      microcirculation plays a role in determining susceptibility toward periprocedural
      MI at the time of elective PCI. The IMR can predict subsequent risk of developing
      myocardial necrosis and may guide adjunctive prevention strategies.

PMID- 22874080
TI  - Size and oxygen passivation induced reversal of photoconducting behaviour in CdS
      nanorods.
AB  - The effect of oxygen adsorption and desorption on the photoconducting gain,
      spectral dependence of quantum efficiency and optical switching was studied in
      CdS nanorods with diameters of 20, 50 and 100 nm. These were found to have an
      increasing degree of crystallinity and consequently a decreasing overall density
      of defects leading to better stoichiometry being maintained. These properties,
      along with the complete depletion of electrons from the nanorod volume and oxygen
      induced passivation of defects, resulted in: (i) a large difference in
      photoconducting gain, (ii) reversal of the photoconducting behaviour on annealing
      in oxygen and a vacuum, and (iii) onset of an absorption edge in the spectral
      dependence of quantum efficiency on oxygen annealing in 20 nm diameter nanorods
      in comparison to the normal photoconducting behaviour expected from an n-type
      semiconductor observed in 50 and 100 nm diameter nanorods. Single CdS nanorod
      devices show stable I-V characteristics in dark and light conditions under a wide
      temperature range and the effect of oxygen and vacuum annealing can be clearly
      observed. The oxygen induced defect passivation observed in this study is
      important for the application of compound semiconductor nanorods in
      optoelectronic devices.

PMID- 22874079
TI  - An Australian twin study of cannabis and other illicit drug use and misuse, and
      other psychopathology.
AB  - Cannabis is the most widely used illicit drug throughout the developed world and
      there is consistent evidence of heritable influences on multiple stages of
      cannabis involvement including initiation of use and abuse/dependence. In this
      paper, we describe the methodology and preliminary results of a large-scale
      interview study of 3,824 young adult twins (born 1972-1979) and their siblings.
      Cannabis use was common with 75.2% of males and 64.7% of females reporting some
      lifetime use of cannabis while 24.5% of males and 11.8% of females reported
      meeting criteria for DSM-IV cannabis abuse or dependence. Rates of other drug use
      disorders and common psychiatric conditions were highly correlated with extent of
      cannabis involvement and there was consistent evidence of heritable influences
      across a range of cannabis phenotypes including early (<=15 years) opportunity to
      use (h 2 = 72%), early (<=16 years) onset use (h 2 = 80%), using cannabis 11+
      times lifetime (h 2 = 76%), and DSM abuse/dependence (h 2 = 72%). Early age of
      onset of cannabis use was strongly associated with increased rates of subsequent
      use of other illicit drugs and with illicit drug abuse/dependence; further
      analyses indicating that some component of this association may have been
      mediated by increasing exposure to and opportunity to use other illicit drugs.

PMID- 22874081
TI  - A 2-year-old child with coronary sinus diverticulum and Wolff-Parkinson-White
      syndrome.
AB  - A 2-year-old child having Wolff-Parkinson-White syndrome presented with recurrent
      drug-refractory tachycardia episodes. On electrophysiological analysis, a
      coronary sinus diverticulum was discovered. The accessory pathway was
      successfully eliminated by radiofrequency ablation within the diverticulum.

PMID- 22874082
TI  - Early weaning is associated with higher neuropeptide Y (NPY) and lower cocaine-
      and amphetamine-regulated transcript (CART) expressions in the paraventricular
      nucleus (PVN) in adulthood.
AB  - The interruption of lactation for a short period, without the use of
      pharmacological substances or maternal separation, causes offspring malnutrition
      and hypoleptinaemia and programmes for metabolic disorders such as higher body
      weight and adiposity, hyperphagia, hyperleptinaemia and central leptin resistance
      in adulthood. Here, in order to clarify the mechanisms underlying the phenotype
      observed in adult early-weaned (EW) rats, we studied the expression of
      neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC)
      and cocaine- and amphetamine-regulated transcript (CART) in different
      hypothalamic nuclei by immunohistochemistry and Western blot. In the EW group,
      the teats of lactating rats were blocked with a bandage to interrupt lactation
      during the last 3 d, while control pups had free access to milk throughout the
      entire lactation period. At age 180 d, EW offspring showed higher NPY staining in
      the paraventricular nucleus (PVN), as well as NPY protein content (+68 %) in
      total hypothalamus than control ones. AgRP showed no changes in staining or
      Western blot. POMC content was not affected; however, its distribution pattern
      was altered. CART-positive cells of EW offspring had lower immunoreactivity
      associated with reduced cell number in the PVN and lower protein content ( - 38
      %) in total hypothalamus. The present data indicate that precocious weaning can
      imprint the neuronal circuitry, especially in the PVN, and cause a long-term
      effect on the expression of specific orexigenic and anorexigenic neuropeptides,
      such as NPY and CART, that can be caused by leptin resistance and are coherent
      with the hyperphagia observed in these animals.

PMID- 22874083
TI  - Is there an association between the home food environment, the local food
      shopping environment and children's fruit and vegetable intake? Results from the
      Dutch INPACT study.
AB  - OBJECTIVE: To examine: (i) the association between home availability of fruit and
      vegetables and children's fruit and vegetable intake; (ii) the association
      between parental perception of the local food shopping environment and the home
      availability of fruit and vegetables; and (iii) whether the home availability of
      fruit and vegetables mediates the association between parental perception of the
      local food environment and children's fruit and vegetable consumption. DESIGN:
      Cross-sectional study. SETTING: A total of ninety-one primary schools in the
      Netherlands. SUBJECTS: In total 1501 primary caregivers completed a questionnaire
      to measure children's fruit and vegetable consumption, home availability of fruit
      and vegetables, parental perceptions of the local food shopping environment
      (price, quality and availability), the child's socio-economic status, the child's
      ethnicity and maternal height and weight. RESULTS: The home availability of fruit
      and vegetables was positively associated with children's fruit and vegetable
      intake (P,0?01 and P,0?001, respectively). Negative parental perceptions of the
      local food shopping environment were associated with less fruit available at home
      (P,0?05, P,0?01 and P,0?05 for price, quality and availability of fruit,
      respectively). No significant associations were found between parental perception
      of the local food shopping environment and children's fruit and vegetable
      consumption. We found no evidence that home availability of fruit and vegetables
      mediates the association between parental perception of the local food
      environment and children's fruit and vegetable intake. CONCLUSIONS: Interventions
      focusing on improving the home availability of fruit and vegetables may help to
      increase children's fruit and vegetable consumption. However, more data are
      required on factors influencing the home availability of fruit and vegetables.

PMID- 22874084
TI  - Risk of deterioration of cardiac function by frequent ventricular ectopy in
      patients without structural heart disease.

PMID- 22874085
TI  - Truth-telling and cancer diagnoses: physician attitudes and practices in Qatar.
AB  - There is limited information regarding physicians' attitudes toward revealing
      cancer diagnoses to patients in the Arab world. Using a questionnaire informed by
      a seminal study carried out by Oken in 1961, our research sought to determine
      present-day disclosure practices in Qatar, identify physician sociodemographic
      variables associated with truth-telling, and outline trends related to future
      practice. A sample of 131 physicians was polled. Although nearly 90% of doctors
      said they would inform cancer patients of their diagnosis, ~66% of respondents
      stated that they made exceptions to their policy, depending on patient
      characteristics. These data suggest that clinical practices are somewhat
      discordant on professed beliefs about the ethical propriety of disclosure.

PMID- 22874087
TI  - Convergent validity of the international physical activity questionnaire (IPAQ):
      meta-analysis.
AB  - OBJECTIVE: The purpose of the present study was to use a meta-analytic approach
      to examine the convergent validity of the international physical activity
      questionnaire (IPAQ). DESIGN: Systematic review by meta-analysis. SETTING: The
      relevant studies were surveyed from five electronic databases. Primary outcomes
      of interest were the product-moment correlation coefficients between IPAQ and
      other instruments. Five separate meta-analyses were performed for each physical
      activity (PA) category of IPAQ: walking, moderate PA (MPA), total moderate PA
      (TMPA), vigorous PA (VPA) and total PA (TPA). The corrected mean effect size
      (ESrho) unaffected by statistical artefacts (i.e., sampling error and
      reliability) was calculated for each PA category. Selected moderator variables
      were length of IPAQ (i.e., short and long form), reference period (i.e., last 7 d
      and usual week), mode of administration (i.e., interviewer and self-reported),
      language (i.e., English and translated) and instruments (i.e., accelerometer,
      pedometer and subjective measure). SUBJECTS: A total of 152 ESrho across five PA
      categories were retrieved from twenty-one studies. RESULTS: The results showed
      small- to medium-sized ESrho (0.27-0.49). The highest value was observed in VPA
      while the lowest value was found in MPA. The ESrho were differentiated by some of
      the moderator variables across PA categories. CONCLUSIONS: The study shows the
      overall convergent validity of IPAQ within each PA category. Some differences in
      degree of convergent validity across PA categories and moderator variables imply
      that different research conditions should be taken into account prior to deciding
      on use of the appropriate type of IPAQ.

PMID- 22874086
TI  - Membrane permeable local anesthetics modulate Na(V)1.5 mechanosensitivity.
AB  - Voltage-gated sodium selective ion channel Na(V)1.5 is expressed in the heart and
      the gastrointestinal tract, which are mechanically active organs. Na(V)1.5 is
      mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local
      anesthetic and antiarrhythmic drugs act upon Na(V)1.5 to modulate activity by
      multiple mechanisms. This study examined whether Na(V)1.5 mechanosensitivity is
      modulated by local anesthetics. Na(V)1.5 channels were expressed in HEK-293
      cells, and mechanosensitivity was tested in cell-attached and excised inside-out
      configurations. Using a novel protocol with paired voltage ladders and short
      pressure pulses, negative patch pressure (-30 mmHg) in both configurations
      produced a hyperpolarizing shift in the half-point of the voltage-dependence of
      activation (V(1/2a)) and inactivation (V(1/2i)) by about -10 mV. Lidocaine (50
      uM) inhibited the pressure-induced shift of V(1/2a) but not V(1/2i). Lidocaine
      inhibited the tonic increase in pressure-induced peak current in a use-dependence
      protocol, but it did not otherwise affect use-dependent block. The local
      anesthetic benzocaine, which does not show use-dependent block, also effectively
      blocked a pressure-induced shift in V(1/2a). Lidocaine inhibited
      mechanosensitivity in Na(V)1.5 at the local anesthetic binding site mutated
      (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect
      mechanosensitivity of F1760A Na(V)1.5 when applied from either side of the
      membrane. These data suggest that the mechanism of lidocaine inhibition of the
      pressure-induced shift in the half-point of voltage-dependence of activation is
      separate from the mechanisms of use-dependent block. Modulation of Na(V)1.5
      mechanosensitivity by the membrane permeable local anesthetics may require
      hydrophobic access and may involve membrane-protein interactions.

PMID- 22874088
TI  - Modelling pertussis transmission to evaluate the effectiveness of an adolescent
      booster in Argentina.
AB  - Due to the current epidemiological situation of pertussis, several countries have
      implemented vaccination strategies that include a booster dose for adolescents.
      Since there is still no evidence showing that the adolescent booster has a
      positive effect on the most vulnerable group represented by infants, it is
      difficult to universalize the recommendation to include such reinforcement. In
      this work we present an age-structured compartmental deterministic model that
      considers the outstanding epidemiological features of the disease in order to
      assess the impact of the booster dose at age 11 years (Tdap booster) to infants.
      To this end, we performed different parameterizations of the model that represent
      distinct possible epidemiological scenarios. The results obtained show that the
      inclusion of a single Tdap dose at age 11 years significantly reduces the
      incidence of the disease within this age group, but has a very low impact on the
      risk group (0-1 year). An effort to improve the coverage of the first dose would
      have a much greater impact on infants. These results hold in the 18 scenarios
      considered, which demonstrates the robustness of these conclusions.

PMID- 22874089
TI  - Adaptation to benzalkonium chloride and ciprofloxacin affects biofilm formation
      potential, efflux pump and haemolysin activity of Escherichia coli of dairy
      origin.
AB  - The present study investigates the effect of adaptive resistance to ciprofloxacin
      (Cip) and benzalkonium chloride (BC) on biofilm formation potential (BFP), efflux
      pump activity (EPA) and haemolysin activity of Escherichia coli isolates of dairy
      origin. All the isolates, irrespective of antimicrobial susceptibility, developed
      significant adaptive resistance (P < 0.05). All the resistant phenotypes
      (antibiotic resistant: AR; & biocide resistant: BR) were stronger biofilm former
      and post-adaptation, an insignificant change was observed in their BFP. Whereas,
      post-adaptation, non-resistant isolates (antibiotic non-resistant: ANR; biocide
      non-resistant: BNR) transformed from poor or moderate to strong biofilm formers.
      Post-adaptive percentage increase in EPA was highly significant in non-resistant
      categories (P < 0.01) and significant at P < 0.05 in BR category. Interestingly,
      post-adaptive increase in EPA in BR isolates was more than that in AR yet, the
      latter exhibited greater adaptive resistance than the former. These findings
      indicated prevalence of some other specific resistance mechanism/s responsible
      for adaptive resistance against Cip. Strain specific variations were observed for
      stability of adaptive resistance and haemolysin activity for all the categories.
      Our findings especially in reference to post-adaptation upgradation of BFP status
      of non-resistant isolates seems to be providing an insight into the process of
      conversion of non-resistant isolate into resistant ones with enhanced BFP. These
      observations emphasize the serious implications of sub-lethal residual levels of
      antimicrobials in food environments and suggest a role of food chain in emergence
      of antimicrobial resistances.

PMID- 22874090
TI  - Psychobiological correlates of improved mental health in patients with
      musculoskeletal pain after a mindfulness-based pain management program.
AB  - OBJECTIVES: Mindfulness-based pain management programs (MBPMs) aim to improve
      mental and physical health in individuals with chronic pain. In this study, we
      investigated whether improvement in mental health might require (1) reduction in
      the sensory pain experience and brain correlates of that experience, and/or (2)
      improved perceptions of the controllability of pain and corresponding brain
      activity related to cognitive control and emotional regulation. METHODS: Twenty
      eight patients with chronic pain were assessed and randomized into an
      intervention group (who attended an 8-wk MBPM) or a control group (treatment-as
      usual), before being reassessed after 8 weeks. Outcome measures included clinical
      pain, perceived control over pain, mental and physical health, and mindfulness.
      Neural activity was measured during the anticipation and experience of acute
      experimental pain, using electroencephalography with source reconstruction.
      RESULTS: Improvements were found in the MBPM group relative to the control group
      in mental health, which related to greater perceived control of pain, but not to
      reductions in clinical or experimental pain ratings. Anticipatory and pain-evoked
      event-related potentials to acute experimental pain were decreased, but sources
      of these event-related potentials were estimated to be in regions that modulate
      emotional responses rather than pain intensity. Mental health and perceived
      control outcomes correlated with reduced anticipatory deactivations of
      dorsolateral prefrontal and somatosensory cortices. DISCUSSION: Increased
      activity in cognitive control regions of the brain during pain anticipation
      related to improved mental health and perceived control over pain, but not to
      decreased pain experience. Greater perceived control may therefore result from
      improved regulation of the emotional response to pain.

PMID- 22874091
TI  - Does mobilization of the upper cervical spine affect pain sensitivity and
      autonomic nervous system function in patients with cervico-craniofacial pain?: A
      randomized-controlled trial.
AB  - OBJECTIVES: The aims were to investigate the effects of anterior-posterior upper
      cervical mobilization (APUCM) on pain modulation in craniofacial and cervical
      regions and its influence on the sympathetic nervous system. METHODS: Thirty-two
      patients with cervico-craniofacial pain of myofascial origin were randomly
      allocated into experimental or placebo groups. Each patient received 3
      treatments. Outcome measures included bilateral pressure pain thresholds assessed
      at craniofacial and cervical points preintervention, after the second
      intervention and after the final treatment. Pain intensity and sympathetic
      nervous system variables (skin conductance, breathing rate, heart rate, and skin
      temperature) were assessed before and immediately after each intervention.
      RESULTS: The pressure pain thresholds in the craniofacial and cervical regions
      significantly increased (P<0.001) and pain intensity significantly decreased
      (P<0.001) in the treatment group compared with placebo. APUCM also produced a
      sympathoexcitatory response demonstrated by a significant increase in skin
      conductance, breathing rate, and heart rate (P<0.001), but not in skin
      temperature (P=0.071), after application of the technique compared with placebo.
      DISCUSSION: This study provided preliminary evidence of a short-term hypoalgesic
      effect of APUCM on craniofacial and cervical regions of patients with cervico
      craniofacial pain of myofascial origin, suggesting that APUCM may cause an
      immediate nociceptive modulation in the trigeminocervical complex. We also
      observed a sympathoexcitatory response, which could be related to the hypoalgesic
      effect induced by the technique, but this aspect should be confirmed in future
      studies.

PMID- 22874092
TI  - Solution phase photolysis of 1,2-dithiane alone and with single-walled carbon
      nanotubes.
AB  - Photolysis of 1,2-dithiane (1) in acetonitrile with single walled carbon
      nanotubes (SWCNTs) was earlier reported to form thiol-functionalized SWCNTs via
      the butane-1,4-dithiyl diradical (2). The present study shows that 2 instead
      undergoes a facile rearrangement to thiophane-2-thiol (6). This photoreaction is
      clean, rapid, and irreversible under 313 nm irradiation. The secondary photolysis
      of 6 with SWCNTs at a shorter wavelength (254 nm) leads to 2-thiophanyl radicals
      8, which derivatize SWCNTs by covalent attachment. Pyrolysis of the resulting
      "sulfurized SWCNTs" affords a mixture of organosulfur compounds, including
      thiophene formed by dehydrogenation. An unknown additional mechanism causes high
      TGA weight loss and a large incorporation of sulfur.

PMID- 22874093
TI  - The hierarchical structure and mechanics of plant materials.
AB  - The cell walls in plants are made up of just four basic building blocks:
      cellulose (the main structural fibre of the plant kingdom) hemicellulose, lignin
      and pectin. Although the microstructure of plant cell walls varies in different
      types of plants, broadly speaking, cellulose fibres reinforce a matrix of
      hemicellulose and either pectin or lignin. The cellular structure of plants
      varies too, from the largely honeycomb-like cells of wood to the closed-cell,
      liquid-filled foam-like parenchyma cells of apples and potatoes and to composites
      of these two cellular structures, as in arborescent palm stems. The arrangement
      of the four basic building blocks in plant cell walls and the variations in
      cellular structure give rise to a remarkably wide range of mechanical properties:
      Young's modulus varies from 0.3 MPa in parenchyma to 30 GPa in the densest palm,
      while the compressive strength varies from 0.3 MPa in parenchyma to over 300 MPa
      in dense palm. The moduli and compressive strength of plant materials span this
      entire range. This study reviews the composition and microstructure of the cell
      wall as well as the cellular structure in three plant materials (wood, parenchyma
      and arborescent palm stems) to explain the wide range in mechanical properties in
      plants as well as their remarkable mechanical efficiency.

PMID- 22874094
TI  - Frequency-dependent fitness induces multistability in coevolutionary dynamics.
AB  - Evolution is simultaneously driven by a number of processes such as mutation,
      competition and random sampling. Understanding which of these processes is
      dominating the collective evolutionary dynamics in dependence on system
      properties is a fundamental aim of theoretical research. Recent works
      quantitatively studied coevolutionary dynamics of competing species with a focus
      on linearly frequency-dependent interactions, derived from a game-theoretic
      viewpoint. However, several aspects of evolutionary dynamics, e.g. limited
      resources, may induce effectively nonlinear frequency dependencies. Here we study
      the impact of nonlinear frequency dependence on evolutionary dynamics in a model
      class that covers linear frequency dependence as a special case. We focus on the
      simplest non-trivial setting of two genotypes and analyse the co-action of
      nonlinear frequency dependence with asymmetric mutation rates. We find that their
      co-action may induce novel metastable states as well as stochastic switching
      dynamics between them. Our results reveal how the different mechanisms of
      mutation, selection and genetic drift contribute to the dynamics and the
      emergence of metastable states, suggesting that multistability is a generic
      feature in systems with frequency-dependent fitness.

PMID- 22874095
TI  - Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective
      agent against UV-induced carcinogenesis.
AB  - Probiotics are live micro-organisms that when administered in adequate amounts
      confer a health benefit on the host. Cell surface molecules of these micro
      organisms are being studied in relation to their ability to interact with the
      host. The cell wall of lactobacilli possesses lipoteichoic acids (LTA) which are
      molecules with immunomodulatory properties. UV radiation (UVR) has been proposed
      as the main cause of skin cancer because of its mutagenic and immunosuppressive
      effects. Photoprotection with some nutrition interventions including probiotics
      has recently been shown. The aim of the present study was to investigate whether
      the oral administration of purified LTA from Lactobacillus rhamnosus GG can
      modulate the immune-suppressive effect of UVR and skin tumour development in
      female Crl:SKH-1-hrBR mice. For this purpose, two irradiation models were
      studied: (1) a chronic irradiation scheme consisting of daily irradiations during
      twenty consecutive days and (2) a long-term irradiation schedule, irradiating the
      animals three times per week, during 34 weeks for tumour development. The results
      showed that T-cells in the inguinal lymph node of LTA-treated mice produced
      higher levels of (1) interferon-gamma and (2) a number of total, helper and
      cytotoxic T-cells compared with non-treated mice. Moreover, a significant delay
      in tumour appearance was found in LTA-treated mice. An increased IgA+ cell number
      was found in the small intestine together with a higher number of activated
      dendritic cells in the mesenteric lymph nodes. The latter results might be
      indicative of a direct effect of LTA in the gut, affecting the cutaneous immune
      system and restoring homeostasis through the gut-skin axis.

PMID- 22874096
TI  - Food photographs in portion size estimation among adolescent Mozambican girls.
AB  - OBJECTIVE: To assess the validity of food photographs in portion size estimation
      among adolescent girls in Mozambique. The study was carried out in preparation
      for the larger ZANE study, which used the 24 h dietary recall method. DESIGN:
      Life-sized photographs of three portion sizes of two staple foods and three
      sauces were produced. Participants ate weighed portions of one staple food and
      one sauce. After the meal, they were asked to estimate the amount of food with
      the aid of the food photographs. SETTING: Zambezia Province, Mozambique.
      SUBJECTS: Ninety-nine girls aged 13-18 years. RESULTS: The mean differences
      between estimated and actual portion sizes relative to the actual portion size
      ranged from 219% to 8% for different foods. The respective mean difference for
      all foods combined was 25% (95% CI 212, 2 %). Especially larger portions of the
      staple foods were often underestimated. For the staple foods, between 62% and 64%
      of the participants were classified into the same thirds of the distribution of
      estimated and actual food consumption and for sauces, the percentages ranged from
      38% to 63%. Bland-Altman plots showed wide limits of agreement. CONCLUSIONS:
      Using life-sized food photographs among adolescent Mozambican girls resulted in a
      rather large variation in the accuracy of individuals' estimates. The ability to
      rank individuals according to their consumption was, however, satisfactory for
      most foods. There seems to be a need to further develop and test food photographs
      used in different populations in Sub-Saharan Africa to improve the accuracy of
      portion size estimates.

PMID- 22874097
TI  - Three-dimensional transthoracic echocardiographic assessment of supramitral ring
      in a young child.
AB  - Three-dimensional echocardiography is an increasingly used method to accurately
      depict congenital heart disease in children. We report the case of a 2-month-old
      girl with supramitral ring. Three-dimensional echocardiography allowed perfect
      visualisation of the fibrous shelf before surgery.

PMID- 22874098
TI  - Food insecurity and household eating patterns among vulnerable American-Indian
      families: associations with caregiver and food consumption characteristics.
AB  - OBJECTIVE: To identify factors associated with food insecurity and household
      eating patterns among American-Indian families with young children. DESIGN: Cross
      sectional survey among households with young children that were receiving
      emergency food services. We collected information on food insecurity levels,
      household eating patterns, experiences with commercial and community food sources
      and demographics, and used multivariate regression techniques to examine
      associations among these variables. SETTING: Four Southwestern American-Indian
      reservation communities. SUBJECTS: A total of 425 parents/caregivers of young
      children completed the survey. RESULTS: Twenty-nine per cent of children and 45 %
      of adults from households participating in the survey were classified as 'food
      insecure'. Larger household size was associated with increased food insecurity
      and worse eating patterns. Older respondents were more likely than younger
      respondents to have children with food insecurity (relative risk = 2.19, P <
      0.001) and less likely to have healthy foods available at home (relative risk =
      0.45, P < 0.01). Consumption of food from food banks, gas station/convenience
      stores or fast-food restaurants was not associated with food insecurity levels.
      Respondents with transportation barriers were 1.46 times more likely to be adult
      food insecure than respondents without transportation barriers (P < 0.001). High
      food costs were significantly associated with greater likelihoods of adult
      (relative risk = 1.47, P < 0.001) and child (relative risk = 1.65, P < 0.001)
      food insecurity. CONCLUSIONS: Interventions for American-Indian communities must
      address challenges such as expense and limited transportation to accessing
      healthy food. Results indicate a need for services targeted to older caregivers
      and larger households. Implications for innovative approaches to promoting
      nutrition among American-Indian communities, including mobile groceries and
      community gardening programmes, are discussed.

PMID- 22874099
TI  - A review of toxoplasmosis in humans and animals in Ethiopia.
AB  - Toxoplasmosis caused by the protozoan parasite, Toxoplasma gondii, is a worldwide
      zoonosis. In this paper published information on toxoplasmosis in humans and
      other animals in Ethiopia is reviewed. Limited data indicate that the prevalence
      of T. gondii in humans in Ethiopia is very high, up to 41% of children aged 1-5
      years were reported to be seropositive. There is little information on
      seroprevalence data in pregnant women and no data on congenital toxoplasmosis in
      children. About 1 million adults in Ethiopia are considered to be infected with
      HIV with less than one-third likely receive highly active antiviral therapy.
      Based on a conservative T. gondii seroprevalence of 50%, thousands might die of
      concurrent opportunistic infections, including toxoplasmosis. However, exact
      figures are not available, and most serological surveys are not current.
      Serological surveys indicate up to 79% of goats and sheep have T. gondii
      antibodies. However, there is no information on losses due to toxoplasmosis in
      livestock or the presence of viable T. gondii in any host in Ethiopia.

PMID- 22874100
TI  - Photochemical oxidation of CVD-grown single layer graphene.
AB  - CVD-grown single layer graphene undergoes rapid photochemical oxidation in the
      presence of ultraviolet light and oxygen. The oxidation results in a homogeneous
      decay of the graphitic material; no nanoscale line cracks or pits were observed
      with an atomic force microscope. The conductivity of the graphene film decreases
      with an increasing degree of oxidation. It is crucial to understand and enhance
      the photochemical stability of graphene for its long term use as a transparent
      conducting material.

PMID- 22874101
TI  - Biodiversity of trematodes associated with amphibians from a variety of habitats
      in Corrientes Province, Argentina.
AB  - The main goals of this study were to compare the richness of parasitic trematodes
      in amphibians with diverse habits (terrestrial, fossorial, semi-aquatic and
      arboreal), and to evaluate whether the composition of the trematode community is
      determined by ecological relationships. Specimens were collected between April
      2001 and December 2006 from a common area (30 ha) in Corrientes Province,
      Argentina. Trematodes of amphibians in this area comprised a total of 19 species,
      and were dominated by common species. Larval trematodes presented highest species
      richness, with the metacercaria of Bursotrema tetracotyloides being dominant in
      the majority (7/9, 78%) of the parasite communities. Adults of the trematode
      Catadiscus inopinatus were dominant in the majority (6/9, 67%) of amphibians. The
      amphibians Leptodactylus latinasus, Leptodactylus bufonius and Scinax nasicus
      presented a high diversity of trematodes, whereas Leptodactylus chaquensis had
      the lowest diversity even though it presented with the highest species richness.
      The patterns of similarity among amphibian species showed groups linking with
      their habitats. Leptodactilid amphibians, with a generalist diet and an active
      foraging strategy showed highest infection rates with adult trematodes. The mean
      richness of trematode species related to host's habitat preferences was higher in
      semi-aquatic amphibians. Results suggest that semi-aquatic amphibians, present in
      both aquatic and terrestrial environments, present a greater diversity of
      parasites as they have a higher rate of exposure to a wider range of prey species
      and, hence, to diverse infective states. The trematode composition is related to
      the diets and mobility of the host, and habitat. 

PMID- 22874103
TI  - The need for more and better palliative care for Muslim patients.

PMID- 22874102
TI  - Quantitative DNA methylation analysis of genes coding for kallikrein-related
      peptidases 6 and 10 as biomarkers for prostate cancer.
AB  - DNA methylation plays an important role in carcinogenesis and is being recognized
      as a promising diagnostic and prognostic biomarker for a variety of malignancies
      including Prostate cancer (PCa). The human kallikrein-related peptidases (KLKs)
      have emerged as an important family of cancer biomarkers, with KLK3, encoding for
      Prostate Specific Antigen, being most recognized. However, few studies have
      examined the epigenetic regulation of KLKs and its implications to PCa. To assess
      the biological effect of DNA methylation on KLK6 and KLK10 expression, we treated
      PC3 and 22RV1 PCa cells with a demethylating drug, 5-aza-2'deoxycytidine, and
      observed increased expression of both KLKs, establishing that DNA methylation
      plays a role in regulating gene expression. Subsequently, we have quantified KLK6
      and KLK10 DNA methylation levels in two independent cohorts of PCa patients
      operated by radical prostatectomy between 2007-2011 (Cohort I, n = 150) and 1998
      2001 (Cohort II, n = 124). In Cohort I, DNA methylation levels of both KLKs were
      significantly higher in cancerous tissue vs. normal. Further, we evaluated the
      relationship between DNA methylation and clinicopathological parameters. KLK6 DNA
      methylation was significantly associated with pathological stage only in Cohort I
      while KLK10 DNA methylation was significantly associated with pathological stage
      in both cohorts. In Cohort II, low KLK10 DNA methylation was associated with
      biochemical recurrence in univariate and multivariate analyses. A similar trend
      for KLK6 DNA methylation was observed. The results suggest that KLK6 and KLK10
      DNA methylation distinguishes organ confined from locally invasive PCa and may
      have prognostic value.

PMID- 22874104
TI  - Circadian rhythm of urinary potassium excretion in patients with CKD.
AB  - AIMS: We previously reported in patients with chronic kidney disease (CKD) that
      the circadian rhythms of blood pressure (BP) and urinary sodium excretion were
      both impaired into non-dipper pattern as renal function deteriorated. However,
      the circadian rhythm of urinary potassium excretion has not been studied in
      relation to renal dysfunction. METHODS: BP and urinary excretion rates of sodium
      (UNaV) and potassium (UKV) were evaluated for daytime and nighttime to estimate
      their circadian rhythms in 83 subjects with CKD. RESULTS: As renal function
      deteriorated, night/day ratios of UNaV and UKV were both increased. Night/day
      ratio of UKV was positively correlated with night/day ratio of UNaV (r = 0.60, p
      < 0.0001). Multiple regression analysis (R2 = 0.37, p < 0.0001) revealed that
      night/day ratio of UKV was determined independently by the night/day ratio of
      UNaV (r = -0.55, p < 0.0001), rather than renal function or night/day ratio of
      BP. CONCLUSIONS: Circadian rhythm of natriuresis was regulated by renal function
      and night/day ratio of BP. On the other hand, the circadian rhythm of urinary
      potassium excretion was primarily determined by neither renal function nor BP,
      but was correlated with that of urinary sodium excretion.

PMID- 22874106
TI  - Factors affecting response and tolerability to ferumoxytol in nondialysis chronic
      kidney disease patients.
AB  - BACKGROUND: Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report
      examines factors affecting hemoglobin response to i.v. ferumoxytol, and the
      relationship between hematologic parameters, concomitant erythropoiesis
      stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients.
      METHODS: A series of post-hoc efficacy and safety analyses were performed using
      pooled data from two identically designed Phase III studies in 608 nondialysis
      CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol
      within 5 +/- 3 days versus oral iron. RESULTS: Ferumoxytol resulted in a
      significant increase in hemoglobin in the presence and absence of ESA, and across
      a range of baseline hemoglobin, transferrin saturation, ferritin, and
      reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were
      similar across quartiles of change in hemoglobin; there were no trends suggesting
      an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin
      or faster rate of hemoglobin rise. There was no meaningful difference in the rate
      of AEs, serious AEs, and cardiovascular AEs between patients receiving or not
      receiving ESA. CONCLUSIONS: These analyses add to the knowledge of predictors of
      response and safety outcomes associated with i.v. iron therapy in nondialysis CKD
      patients.

PMID- 22874105
TI  - Apolipoprotein E and kidney function in older adults.
AB  - BACKGROUND: Previous studies suggest that the epsilon4 and epsilon2 alleles of
      apolipoprotein E (APOE) may be associated with decreased and increased risks of
      CKD, respectively, but there are limited data in older adults. We evaluated the
      associations of apolipoprotein E alleles with kidney function among older adults
      in the cardiovascular health study (CHS). METHODS: Caucasian participants had
      APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n
      = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for
      longitudinal analysis). APOE variation was evaluated as an additive model with
      number of epsilon2, epsilon3 and epsilon4 alleles. GFR was estimated using the
      CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation
      (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m2. The
      secondary outcome was rapid progression defined by annual loss of eGFR > 3
      ml/min/1.73 m2. RESULTS: Mean eGFRcreat was 72 ml/min/1.73 m2 (25% CKD). Compared
      with the epsilon3 allele, the APOE epsilon4 allele was associated with reduced
      risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval
      (CI) 0.79 (0.67 - 0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68 - 0.96)
      per allele. Results were consistent using eGFRcys. There was no association of
      the epsilon2 allele with CKD or between the apolipoprotein E gene with rapid
      progression. CONCLUSIONS: The apolipoprotein epsilon4 allele was associated with
      lower odds of CKD in elderly Caucasian individuals. Future research should
      confirm these findings in other races and explore mechanisms to explain these
      results.

PMID- 22874107
TI  - Initial use of once-monthly administration of C.E.R.A. is effective and safe in
      correcting renal anemia in non-dialysis patients: the MERCUR trial.
AB  - BACKGROUND: Continuous erythropoietin receptor activator (C.E.R.A.) is routinely
      given once every 2 weeks to correct hemoglobin (Hb) level, but monthly use is
      recommended in the maintenance phase. PATIENTS AND METHODS: In an open-label,
      single- arm, multicenter trial, 184 ESA-naive non-dialysis patients with renal
      anemia (Hb <= 10.5 g/dl) received C.E.R.A. monthly from the start of therapy. The
      trial comprised a titration phase (Months 2 - 7) and an evaluation phase (Months
      8 - 9). Mean Hb increased from 9.8 +/- 0.7 g/dl at baseline to 11.5 +/- 1.1 g/ dl
      during the evaluation phase (mean change 1.6 +/- 1.1 g/dl; 95% CI 1.4 - 1.8
      g/dl). Among patients with two Hb values available during the evaluation phase,
      18.1% (19/105) were maintained at 11.0 - 12.0 g/dl and 49.5% (52/105) at 11.0 -
      13.0 g/dl. 20 patients started dialysis and received C.E.R.A during the titration
      phase. RESULTS: Their mean Hb increased from 10.6 +/- 1.6 g/dl (last pre-dialysis
      value) to 11.3 +/- 1.6 g/dl. Nine patients (4.9%) experienced one adverse event
      with a suspected relation to C.E.R.A.; 5 were graded serious. 54 patients (29.3%)
      discontinued the study (22 for adverse events). CONCLUSION: Although no control
      arm was included, such that robust comparisons cannot be drawn, these results
      suggest that C.E.R.A. therapy can be initiated once a month in non-dialysis CKD
      patients with renal anemia without appearing to compromise the rate or degree of
      Hb correction.

PMID- 22874108
TI  - Prevalence of chronic kidney disease and its risk factors among family practice
      patients in Lithuania.
AB  - BACKGROUND: Early detection of chronic kidney disease (CKD) by the first line is
      essential. In many countries, serum creatinine measurements are reimbursed in
      home practice. In Lithuania however, until recently they were not. Therefore, the
      aim of this study was to assess the prevalence of risk factors of CKD in primary
      care patients, to evaluate the awareness of family practitioners and, finally, to
      investigate renal function parameters in patients at risk. METHODS: We reviewed
      the charts of adult patients (n = 4,082) from four home practices in Kaunas and
      identified patients at increased risk for CKD (severe arterial hypertension,
      diabetes, cardiovascular disease (CVD), other causes of kidney damage). We noted
      age and gender in all patients, and renal function measurements performed over
      the preceding 24 months in the patients at risk. In the second part, we assessed
      nephrological status (history, clinical characteristics, serum creatinine,
      dipstick urinalysis and microalbuminuria, estimated glomerular filtration rate
      (eGFR) by the abbreviated MDRD formula) for those at risk who were referred by
      their family practitioners. RESULTS: In total, 458 (11.2%) patients had risk
      factors for CKD. Severe arterial hypertension was found in 62.6% of these
      patients, diabetes in 20.9%, CVD in 6.2% and 34.5% had a history of kidney
      damage. Kidney tests had been performed by family practioner in 59% of these
      patients. Only 30.3% of these patients were referred to the nephrologist and an
      additional 20.1% came after receiving an invitation letter. eGFR < 60 ml/min/1.73
      m2 was found in 42.9% of these patients, 23.4% had microalbuminuria and 7.8%
      overt proteinuria. Optimal blood pressure control (< 130/85 mmHg) was achieved in
      a minority (10.4%). 79.7% had abnormal BMI, 39% used no ACEI/ARB, and 16% were
      smokers. Kidney dysfunction was associated with a higher prevalence of
      microalbuminuria and a lower use of ACEI/ ARB. CONCLUSIONS: Risk factors for CKD
      were present in 11% of the patients in this primary care cohort. Kidney
      dysfunction was found in almost half of the patients at risk. However, awareness
      of this problem by family practitioners was low.

PMID- 22874109
TI  - Clinical and pathological features of dense deposit disease in Chinese patients.
AB  - AIMS: Dense deposit disease (DDD) is a rare disease that has no universally
      effective treatment. Herein we explore the clinical and pathological features of
      DDD in Chinese patients and the therapeutic effect of Tripterygium wilfordii
      (TW). MATERIALS AND METHODS: Clinical and pathological data of 10 Chinese
      patients with biopsy-proved DDD were collected and analyzed retrospectively.
      RESULTS: The patients consisted of 6 males and 4 females. All of them had heavy
      proteinuria and microscopic hematuria. Gross hematuria, renal insufficiency,
      anemia, hypertension and low serum complement 3 (C3) occurred in 3, 3, 5, 6 and 8
      cases, respectively. Under light microscopy (LM), 8 cases exhibited
      membranoproliferative glomerulonephritis (MPGN). Periodic acid-Schiff (PAS) stain
      disclosed intense PAS-positive bright ribbon-like thickening of glomerular
      basement membranes (GBM). Immunofluorescence mainly showed diffuse fine granular
      and short linear deposition of C3 along the glomerular capillary wall. Under
      electron microscopy, ribbon-like electrondense intramembranous deposits were
      identified in the lamina densa of the GBM, along the tubule basement membranes
      (TBM) and wall of Bowman's capsule. Before admission, 6 cases were treated with
      prednisone, cyclophosphamide and/or cyclosporin A with no response. Proteinuria
      in 8 cases who received TW during the course decreased at different degrees.
      CONCLUSIONS: The clinical and pathological features in DDD patients were various.
      The effect of TW in patients with DDD merits further investigation.

PMID- 22874110
TI  - Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in
      hemodialysis patients: a crossover study.
AB  - BACKGROUND: Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder
      and shows a comparable effect with other phosphate binders on hyperphosphatemia
      in dialysis patients. LC also contributes to a reduced oral calcium load compared
      with calcium carbonate (CaC) treatment. However, no crossover studies which
      compare the influence on serum calcium level between treatments with LC and CaC
      in hemodialysis (HD) patients have been carried out. METHODS: After washout for 2
      weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3
      months. Thereafter, patients underwent a second 2-week washout period and were
      switched to the alternative binder for the next 3 months. Mineral and bone
      metabolism markers were measured with the changes of vitamin D doses. RESULTS:
      The serum phosphate level showed a similar decrease from baseline to 3 months in
      both groups. During the study periods, hypercalcemia was observed only in
      patients taking CaC. The dose of vitamin D analogue was increased more frequently
      in the patients of the LC group compared with LC group. The iPTH level showed a
      significant decrease in the CaC group, but not in the LC group. Serum levels of
      BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF
      23 level showed a significant decrease. CONCLUSION: LC effectively reduced the
      serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be
      increased without hypercalcemia in HD patients. LC is one of the useful phosphate
      binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

PMID- 22874111
TI  - The frequency of Fabry disease with the E66Q variant in the alpha-galactosidase A
      gene in Japanese dialysis patients: a case report and a literature review.
AB  - Fabry disease (FD) is an Xlinked disorder resulting in a deficiency in alpha
      galactosidase A (alpha-Gal) activity. FD is one of the causes of progressive
      renal dysfunction, but its diagnosis is often delayed or missed completely. We
      herein report the case of a 70-year-old male who had been receiving hemodialysis
      (HD) for 23 y who was diagnosed with FD after his participation in a screening
      program for plasma alpha-Gal activity for 892 HD patients. He had a low plasma
      alpha-Gal activity level and was demonstrated to have an E66Q mutation in exon 2
      of the alpha-Gal gene. One of his daughters had the same mutation. The proband
      died due to aspiration pneumonia before receiving enzyme replacement therapy. We
      reviewed previous studies and found E66Q mutation in 36% of Japanese FD patients
      on HD including the present case. The clinical characteristics of E66Q variant
      are also discussed.

PMID- 22874112
TI  - Drug-induced TINU syndrome and genetic characterization.
AB  - Tubulointerstitial nephritis and uveitis (TINU) syndrome is due to a
      disregulation of cell-mediated immunity and genetical predisposition due a
      particular molecular characterization. We report the case of a 50-year-old woman
      who was admitted for acute renal failure. She had recently taken flurbiprofen for
      10 d for recurrent bronchitis. A renal biopsy revealed acute tubulointerstitial
      nephritis. Prednisone was started and prognosis was favorable. Three months later
      the patient developed transitory blurred vision. The diagnosis was bilateral
      uveitis and she received topic and systemic corticosteroid therapy, with
      resolution of ocular symptoms. Recurrent episodes of uveitis experienced during
      the next 12 months were treated with same therapy. Genomic haplotype in our
      patients was HLA A*0278/2631,-B*1517/3802,- Cw*0701/1202, -DRB1*0101/1359 (DRB3*
      52), -DQA1*0102/0102, DQB1*0603/0603. TINU syndrome is characterized by
      tubulointerstitial nephritis that tends to be selflimiting, whereas uveitis tends
      to relapse. HLA-DQA1*01 and -DQB1*06 haplotypes are strongly associated with TINU
      syndrome. This is the first report of TINU syndrome induced by flubiprofen
      intake. Our case emphasizes the importance of the association between drug
      exposure and strong susceptibility to TINU syndrome giving the molecular
      characterization.

PMID- 22874113
TI  - A rare cause of childhood-onset nephrotic syndrome: lipoprotein glomerulopathy.
AB  - We report on a 12-year-old female patient with lipoprotein glomerulopathy (LPG)
      who was proven to be heterozygous for ApoE2 Kyoto (Arg25Cys). Her family members
      have the same variant but do not have obvious signs of renal function impairment.
      Six months of treatment with a statin caused significant clinical improvement in
      the lipid profile, proteinuria, and renal function. Our case suggests that
      administration of a statin is a potential therapeutic strategy for improving
      nephrotic syndrome in patients with LPG.

PMID- 22874114
TI  - From placenta to podocyte: vascular and podocyte pathophysiology in preeclampsia.
AB  - Preeclampsia is a disorder of hypertension and proteinuria that affects 6 - 8% of
      normal pregnancies. Recent research has revealed many molecular mechanisms that
      may contribute to systemic endothelial dysfunction, glomerular capillary
      endotheliosis, dysregulation of the glomerular filtration apparatus, and podocyte
      loss. An ischemic placenta elaborates soluble FMS-like tyrosine kinase 1 (sFlt
      1), a soluble receptor for vascular endothelial growth factor (VEGF). A variety
      of mediators, including nitric oxide, Angiotensin II receptor autoantibodies
      (AT1AA), and endothelin-1 may serve to maintain placental ischemia and systemic
      endothelial dysfunction. Endothelin-1 and decreased vascular endothelial growth
      factor may adversely affect overall expression and distribution of podocyte foot
      process proteins, leading to proteinuria. Podocyte derangements may lead to
      podocyte apoptosis and loss, as evidenced by the detection of live podocytes and
      podocyte products in the urine of preeclamptic women. In this review, we explore
      recent research elucidating the interactions of placenta, endothelium, and
      podocyte leading to the clinical syndrome of preeclampsia.

PMID- 22874115
TI  - Coagulopathies in orthopaedics: links to inflammation and the potential of
      individualizing treatment strategies.
AB  - Orthopaedic patients are at risk for developing pathologic imbalances of
      coagulation factors characterized by phases of both hypocoagulability and
      hypercoagulability. Complications from "hypocoagulability" include life
      threatening hemorrhage, wound hematoma, and poor wound healing. Complications due
      to "hypercoagulability" include deep venous thrombosis, pulmonary embolus, and
      disseminated intravascular coagulation. In addition, coagulation imbalance that
      favors the production of procoagulant factors may lead to excessive inflammation
      and contribute to systemic inflammatory response syndrome, acute respiratory
      distress syndrome, multiple organ dysfunction syndrome, and death. Optimally, the
      goal of individualized treatment of coagulopathies in orthopaedic patients should
      be to achieve efficient healing while avoiding the morbidities associated with
      imbalance of coagulation and inflammation. Such individualized and time-sensitive
      measures of coagulation status require rapid, accurate, qualitative, and
      quantitative assessment of the critical balance of the coagulation system.
      Commonly used coagulation tests (prothrombin time and activated partial
      thromboplastin time) are incapable of determining this balance. An alternative to
      is to perform thrombin generation assays. The greatest advantage of thrombin
      generation assays over traditional coagulation tests is their ability to detect
      hypercoagulability, the balance of procoagulant and anticoagulant factors, and
      the effect of all pharmaceutical anticoagulants. Further clinical investigations
      are warranted to develop and refine the thrombin generation assays to help
      predict clinical complications related to coagulation imbalances. In addition,
      future testing will help define the prothrombotic period allowing for appropriate
      initiation and cessation of anticoagulant pharmaceuticals. These subsequent
      studies have the potential to allow the development of a real-time coagulation
      monitoring strategy that could have paramount implications in the management of
      postoperative patients.

PMID- 22874116
TI  - (Effect) size matters!

PMID- 22874117
TI  - Comparison of the antimicrobial effect of chlorhexidine and saline for irrigating
      a contaminated open fracture model.
AB  - OBJECTIVES: The objective of this study is to compare antimicrobial effect of
      irrigation with chlorhexidine gluconate (CHG) to saline in an animal model.
      METHODS: This study used a segmental defect rat femur model contaminated with
      Staphylococcus aureus and treated 6 hours after injury with debridement and
      irrigation with 60 mL of fluid delivered at low pressure. In study groups of 10
      animals each, 3 concentrations of CHG (0.5%, 0.05%, and 0.005%) were used and a
      group irrigated with 0.05% CHG and then saline and a control group treated with
      saline only. After irrigation the wounds were closed, and the rats were
      recovered. Fourteen days later, bone and implants were harvested for separate
      microbiological analysis. RESULTS: There was no statistical difference detected
      between the subsequent presence or quantity of bacteria after irrigation, with
      aqueous CHG at a range of concentrations comparing irrigation with saline alone.
      CONCLUSIONS: This study does not support the use of CHG as an irrigant. This may
      be due to the antibacterial effect of CHG being offset by the associated host
      tissue toxicity. Host tissue damage from high irrigation pressures and cytotoxic
      solutions has been shown to allow bacteria to thrive. We believe this is due to a
      "rebound" of bacteria growth in a wound bed containing small quantities of
      necrotic tissue damaged by CHG exposure.

PMID- 22874118
TI  - Combined pelvic ring disruption and acetabular fracture: associated injury
      patterns in 40 patients.
AB  - OBJECTIVES: Combined pelvic ring disruptions and acetabular fractures are thought
      to be uncommon. Our objectives were to characterize concomitant injury patterns
      and to compare them with historically observed rates for each injury in
      isolation. DESIGN: Retrospective review comparing a study group with historical
      controls. Fracture patterns were compared with our institution's isolated injury
      patterns and with isolated injury patterns of other published series. SETTING:
      Level I academic medical center. PATIENTS: Between 1997 and 2001, 854 pelvic ring
      disruptions and 457 acetabular fractures were evaluated. Forty patients sustained
      combined injuries. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Fracture
      patterns, Injury Severity Scores, and mortality rates. RESULTS: Our series of
      combined injuries included 5% posterior wall fractures. This was significantly
      different from the 30% incidence of posterior wall fractures among isolated
      acetabular fractures at our institution (P < 0.006). No posterior column or
      posterior column with associated posterior wall fractures occurred. Fifty-three
      percent of the patients sustained anterior-posterior compression pelvic ring
      injuries, exceeding our center's 19% norm for isolated pelvic ring injuries (P <
      0.001). For combined injuries, the mean injury severity score was 27.9 and the
      overall mortality rate was 13%. Early death occurred in 19% of patients with
      combined anterior-posterior compression injuries and 6% with lateral compression
      injuries. CONCLUSIONS: Patients with combined pelvic and acetabular injuries have
      multiple system injuries and high Injury Severity Scores. Fracture patterns
      differ from those observed with isolated injuries. Posterior acetabular fractures
      are uncommon components. Anterior-posterior compression pelvic injuries seem much
      more frequent in cases of combined injuries than isolated injuries and are
      associated with high mortality rates. LEVEL OF EVIDENCE: Prognostic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22874119
TI  - Preparing for the road ahead.
AB  - The practice of orthopaedic trauma has been considered "a young person's game,"
      but there are many before you who have maintained a fulfilling, successful, and
      long-lasting career in orthopaedic trauma. The keys to longevity are avoiding
      burnout and developing a supportive team of practice partners, mentors, and other
      colleagues. It is important to develop and continually refine a series of "5-year
      plans" to make sure that you are progressing toward your goals. Develop a
      specialized niche in 1 or 2 areas that fills an open gap in your community and in
      which you can really flourish. Finally, it is critical to maintain your skills in
      a trauma-related discipline that can be built into an elective practice that
      provides referrals, fills the gaps when trauma slows, and is something that you
      enjoy.

PMID- 22874120
TI  - Does tracking of dietary behaviours differ by parental education in children
      during the transition into adolescence?
AB  - OBJECTIVE: The present study investigates the changes and tracking of dietary
      behaviours in Norwegian 11-year-olds and examines the association between
      parental education and dietary tracking over a time period of 20 months. DESIGN:
      Longitudinal data from the Norwegian HEalth In Adolescents (HEIA) cohort study
      followed up at three time points (2007-2009). SETTING: Intakes of fruits,
      vegetables and snacks were assessed by frequency and intakes of sugar-sweetened
      soft drinks and squash were assessed by frequency and amount. Tracking of dietary
      behaviours was assessed by adolescents' relative position in rank over time and
      Cohen's kappa was used to measure tracking coefficients. Multinomial logistic
      regression analyses were performed to assess the association between parental
      education and the tracking of dietary behaviours. SUBJECTS: In total, 885
      adolescents from the HEIA cohort study participated by answering Internet-based
      questionnaires at three time points. RESULTS: The results indicated that boys and
      girls maintained their relative position in rank of dietary intake over time,
      when grouped by baseline consumption. Fair to moderate tracking coefficients of
      dietary variables were observed. An inverse association was found between
      parental education and stability of soft drink and squash consumption during the
      20 months. CONCLUSIONS: The observed tracking pattern indicates the importance of
      promoting healthy dietary behaviours at an even earlier age. Furthermore,
      interventions should focus particularly on adolescents from families with low
      parental education and their consumption of sugar-sweetened beverages.

PMID- 22874121
TI  - Gene expression analysis of the liver and skeletal muscle of psyllium-treated
      mice.
AB  - Psyllium, a dietary fibre rich in soluble components, has both cholesterol- and
      TAG-lowering effects. Many studies have verified these actions using liver
      samples, whereas little information is available on the effects of psyllium
      treatment on other organs. The purpose of the present study was to evaluate the
      possible beneficial effects of psyllium. We investigated the gene expression
      profiles of both liver and skeletal muscle using DNA microarrays. C57BL/6J mice
      were fed a low-fat diet (LFD; 7 % fat), a high-fat diet (HFD; 40 % fat) or a HFD
      with psyllium (40 % fat+5 % psyllium; HFD+Psy) for 10 weeks. Body weights and
      food intake were measured weekly. After 10 weeks, the mice were killed and
      tissues were collected. Adipose tissues were weighed, and plasma total
      cholesterol and TAG blood glucose levels were measured. The expression levels of
      genes involved in glycolysis, gluconeogenesis, glucose transport and fatty acid
      metabolism were measured by DNA microarray in the liver and skeletal muscle. In
      the HFD+Psy group, plasma total cholesterol, TAG and blood glucose levels
      significantly decreased. There was a significant reduction in the relative weight
      of the epididymal and retroperitoneal fat tissue depots in mice fed the HFD+Psy.
      The expression levels of genes involved in fatty acid oxidation and lipid
      transport were significantly up-regulated in the skeletal muscle of the HFD+Psy
      group. This result suggests that psyllium stimulates lipid transport and fatty
      acid oxidation in the muscle. In conclusion, the present study demonstrates that
      psyllium can promote lipid consumption in the skeletal muscle; and this effect
      would create a slightly insufficient glucose state in the liver.

PMID- 22874122
TI  - Shunt reduction to pulmonary arteriovenous malformations using a modified covered
      stent.
AB  - Pulmonary arteriovenous malformations in patients with congenital heart disease
      have been associated with interruption of hepatic venous return to the lungs. We
      report a novel technique to improve systemic saturation using a modified covered
      stent in a patient with unilateral left pulmonary arteriovenous malformations in
      the setting of a Fontan circulation.

PMID- 22874123
TI  - Pareto evolution of gene networks: an algorithm to optimize multiple fitness
      objectives.
AB  - The computational evolution of gene networks functions like a forward genetic
      screen to generate, without preconceptions, all networks that can be assembled
      from a defined list of parts to implement a given function. Frequently networks
      are subject to multiple design criteria that cannot all be optimized
      simultaneously. To explore how these tradeoffs interact with evolution, we
      implement Pareto optimization in the context of gene network evolution. In
      response to a temporal pulse of a signal, we evolve networks whose output turns
      on slowly after the pulse begins, and shuts down rapidly when the pulse
      terminates. The best performing networks under our conditions do not fall into
      categories such as feed forward and negative feedback that also encode the input
      output relation we used for selection. Pareto evolution can more efficiently
      search the space of networks than optimization based on a single ad hoc
      combination of the design criteria.

PMID- 22874124
TI  - Mitral valve prolapse:  role of 3D echocardiography in diagnosis.
AB  - PURPOSE OF REVIEW: To review the utility and the latest developments in three
      dimensional (3D) echocardiography of mitral valve prolapse. RECENT FINDINGS:
      Although 3D echocardiography was invented in 1974, it did not gain wide clinical
      acceptance until the introduction of real-time 3D echocardiography in the first
      decade of the 21st century. Driven by improvements in probe technology and
      increases in computing power, 3D echocardiography now provides unprecedented
      images of mitral valve prolapse and its associated mitral regurgitation with no
      or minimal requirements for image post processing. SUMMARY: 3D echocardiography
      has become the echocardiographic modality of choice for establishing the
      diagnosis, describing the precise anatomy, and visualization of mitral
      regurgitant jets in mitral valve prolapse. 3D echocardiography is becoming
      indispensable in guiding surgical and percutaneous methods of mitral valve repair
      and replacement.

PMID- 22874125
TI  - Three-dimensional echocardiography to quantify mitral valve regurgitation.
AB  - PURPOSE OF REVIEW: Current three-dimensional echocardiographic technology,
      including live three-dimensional transesophageal echocardiography and single-beat
      three-dimensional color Doppler imaging, are providing valuable new insight into
      the mechanism and quantification of mitral valve regurgitation. RECENT FINDINGS:
      We discuss recent applications of three-dimensional volumetric leaflet imaging
      with emphasis on the distinction between organic and functional mitral
      regurgitation. We also discuss the added benefit of current and emerging three
      dimensional color Doppler methods for the quantification of mitral valve
      regurgitation severity. The limitations of the two-dimensional proximal
      isovelocity surface area method are discussed, along with potential solutions
      provided by three-dimensional color Doppler imaging methods. Methods to directly
      measure the regurgitant jet vena contracta area are presented, along with recent
      clinical studies comparing this method with two-dimensional Doppler and cardiac
      MRI reference standards. SUMMARY: The use of three-dimensional color Doppler
      methods has now been well validated for the accurate and reproducible
      quantification of mitral valve regurgitation severity. These newer tools are now
      clinically available and should be incorporated into the routine Doppler
      assessment of mitral valve regurgitation severity.

PMID- 22874126
TI  - Cardiac magnetic resonance for mitral regurgitation diagnosis:  when is it
      needed?
AB  - PURPOSE OF REVIEW: Mitral regurgitation is a growing public concern affecting a
      large number of individuals in the United States. Although echocardiography is
      the primary imaging modality for assessment of mitral regurgitation, it may be
      inadequate or suboptimal for a variety of reasons. In these instances, cardiac
      magnetic resonance (CMR) may be useful. RECENT FINDINGS: The diagnostic
      capabilities of CMR have increased substantially over the past 20 years due to
      hardware and software advances. Today, CMR is useful in providing clinicians with
      a number of important pieces of information in the assessment of mitral
      regurgitation. It has emerged as a robust modality to quantify mitral
      regurgitation severity. In addition, it is able to provide insights into the
      mechanism of mitral regurgitation and also to help discern the consequences of
      the regurgitant lesion on left ventricular performance. SUMMARY: CMR has a number
      of unique advantages over other imaging modalities as there are no issues of
      image quality from inadequate imaging windows or body habitus. In most instances,
      information can be obtained noninvasively, without the need for intravenous
      contrast agents or ionizing radiation.

PMID- 22874127
TI  - The aspirin controversy in primary prevention.
AB  - PURPOSE OF REVIEW: Apparently conflicting meta-analysis results have led to
      renewed debate about the role of aspirin for the primary prevention of
      cardiovascular disease. We review the results of meta-analyses comparing aspirin
      with placebo or no aspirin for the primary prevention of cardiovascular disease
      and critically evaluate whether aspirin provides a net benefit. RECENT FINDINGS:
      The results of four independently conducted meta-analyses between 2009 and 2012
      involving between 95 000 and 102 621 individuals at low risk of cardiovascular
      disease are consistent with the results of the 2002 Antithrombotic Trialists'
      Collaboration meta-analysis, which found that aspirin reduces cardiovascular
      events primarily by reducing nonfatal myocardial infarction (MI). There is no
      convincing evidence that aspirin reduces cardiovascular mortality, but estimates
      from all of the meta-analyses suggest a modest reduction in all-cause mortality.
      Aspirin reduces ischaemic stroke but increases haemorrhagic stroke and major
      bleeding. SUMMARY: The meta-analysis results consistently indicate that, in
      individuals at low risk for cardiovascular disease, aspirin reduces the risk of
      MI at the cost of an increase in major bleeding and produces a modest nominally
      significant reduction in total mortality. These results suggest that
      recommendations for primary prevention with aspirin should be individualized,
      taking into account the balance between benefits and risks and individual values
      and preferences.

PMID- 22874128
TI  - Personalizing cardiovascular disease prevention among breast cancer survivors.
AB  - PURPOSE OF REVIEW: With the advancement of breast cancer therapies, most women
      diagnosed with breast cancer in the United States are now expected to survive
      their disease, and management of competing comorbidities, particularly
      cardiovascular disease (CVD), is crucial. RECENT FINDINGS: Recent studies have
      suggested that CVD is the most common cause of death for women diagnosed with
      ductal carcinoma in situ or stage I disease and for women aged more than 80 years
      with stage II disease. Various breast cancer therapies, including targeted
      therapies, can accentuate CVD risk; referrals for cardiology opinion are not
      uncommon at the time at which treatment options are under consideration. The use
      of less cardiotoxic alternatives, such as liposomal doxorubicin, and intensity
      modulated radiation therapy should be considered when appropriate. Doppler
      myocardial imaging and cardiac MRI might allow early recognition of
      cardiotoxicity. SUMMARY: It is important to weigh both the risk of CVD and that
      of breast cancer recurrence in a breast cancer survivor. Certain interventions
      for the primary prevention of CVD, including diet, physical activity, smoking
      cessation and aspirin, can reduce breast cancer risk as well. The management of
      CVD risk factors is of increasing importance in the management of breast cancer
      survivors.

PMID- 22874129
TI  - Current world literature.

PMID- 22874131
TI  - Functional characterization of the rod visual pigment of the echidna
      (Tachyglossus aculeatus), a basal mammal.
AB  - Monotremes are the most basal egg-laying mammals comprised of two extant genera,
      which are largely nocturnal. Visual pigments, the first step in the sensory
      transduction cascade in photoreceptors of the eye, have been examined in a
      variety of vertebrates, but little work has been done to study the rhodopsin of
      monotremes. We isolated the rhodopsin gene of the nocturnal short-beaked echidna
      (Tachyglossus aculeatus) and expressed and functionally characterized the protein
      in vitro. Three mutants were also expressed and characterized: N83D, an important
      site for spectral tuning and metarhodopsin kinetics, and two sites with amino
      acids unique to the echidna (T158A and F169A). The lambda(max) of echidna
      rhodopsin (497.9 +/- 1.1 nm) did not vary significantly in either T158A (498.0 +/
      1.3 nm) or F169A (499.4 +/- 0.1 nm) but was redshifted in N83D (503.8 +/- 1.5
      nm). Unlike other mammalian rhodopsins, echidna rhodopsin did react when exposed
      to hydroxylamine, although not as fast as cone opsins. The retinal release rate
      of light-activated echidna rhodopsin, as measured by fluorescence spectroscopy,
      had a half-life of 9.5 +/- 2.6 min-1, which is significantly shorter than that of
      bovine rhodopsin. The half-life of the N83D mutant was 5.1 +/- 0.1 min-1, even
      shorter than wild type. Our results show that with respect to hydroxylamine
      sensitivity and retinal release, the wild-type echidna rhodopsin displays major
      differences to all previously characterized mammalian rhodopsins and appears more
      similar to other nonmammalian vertebrate rhodopsins such as chicken and anole.
      However, our N83D mutagenesis results suggest that this site may mediate
      adaptation in the echidna to dim light environments, possibly via increased
      stability of light-activated intermediates. This study is the first
      characterization of a rhodopsin from a most basal mammal and indicates that there
      might be more functional variation in mammalian rhodopsins than previously
      assumed.

PMID- 22874132
TI  - Ethnicity, race, and advance directives in an inpatient palliative care
      consultation service.
AB  - OBJECTIVE: Although race and ethnic background are known to be important factors
      in the completion of advance directives, there is a dearth of literature
      specifically investigating the effect of race and ethnicity on advance directive
      completion rate after palliative care consultation (PCC). METHOD: A chart review
      of all patients seen by the PCC service in an academic hospital over a 9-month
      period was performed. Data were compiled using gender, race, ethnicity, religion,
      and primary diagnosis. For this study, advance directives were defined as: "Do
      Not Resuscitate" (DNR) and/or "Do Not Intubate" (DNI). RESULTS: Of the 400
      medical records reviewed, 57% of patients were female and 71.3% documented their
      religion as Christian. The most common documented diagnosis was cancer (39.5%).
      Forty-seven percent reported their race as white. White patients completed more
      advance directives than did nonwhite patients both before (25.67% vs. 12.68%) and
      after (59.36% vs. 40.84%) PCC. There was a significantly higher proportion of
      whites who signed an advance directive after a PCC than of nonwhites (p = 0.021);
      of the 139 whites who did not have an advance directive at admission, 63 signed
      an advance directive after a PCC compared with 186/60 nonwhites (45% vs. 32%,
      respectively, p = 0.021). Further analysis revealed that African Americans
      differed from whites in the likelihood of advance directive execution rates pre
      PCC, but not post-PCC. SIGNIFICANCE OF RESULTS: This study demonstrates the
      impact of a PCC on the completion of advance directives, on both whites and
      nonwhites. The PCC Intervention significantly reduced differences between whites
      and African Americans in completing advance directives, which have been
      consistently documented in the end-of-life literature.

PMID- 22874133
TI  - Management of recurrent acute otitis media in children: systematic review of the
      effect of different interventions on otitis media recurrence, recurrence
      frequency and total recurrence time.
AB  - OBJECTIVE: To conduct a systematic review comparing the effect of three
      interventions (prophylactic antibiotics, tympanostomy tube insertion and
      adenoidectomy) on otitis media recurrence, recurrence frequency and total
      recurrence time. METHODS: Literature on recurrent otitis media was identified
      using the PubMed and Scopus search engines for the period January 1990 to March
      2011. A hand search of the reference lists of relevant articles and textbooks was
      conducted to identify additional studies. Randomised, controlled trials with a
      minimum of 40 children and follow up of at least 12 months were included.
      RESULTS: Eighteen publications were identified. Each was assessed using preset
      inclusion criteria; seven publications met these criteria. CONCLUSION:
      Prophylactic antibiotics are effective in reducing otitis media recurrence,
      recurrence frequency and total recurrence time. Tympanostomy tube insertion
      failed to reduce the prevalence of otitis media recurrence, but reduced the
      recurrence frequency and total recurrence time. Adenoidectomy reduced otitis
      media recurrence; results on otitis media recurrence frequency differed but on
      average there was a reduction; however, the two studies with relevant data on
      total recurrence time had contradictory results.

PMID- 22874134
TI  - A perspective on the evidence regarding methicillin-resistant Staphylococcus
      aureus surveillance.
AB  - Two prominent studies have been used by policy makers to prevent the enactment of
      standards of care regarding active surveillance of patients with methicillin
      resistant Staphylococcus aureus in hospital settings. In this brief review and
      perspective of those studies, we contend that both studies have serious
      limitations (i.e., the intervention group was not given optimal intervention)
      that may not have been scrutinized by many policy makers, health officials, and
      other researchers. These studies seem to have had a disproportionate impact on
      health-care policy despite their limitations. Furthermore, health-care policy and
      treatment standards need to reflect the preponderance of evidence with
      appropriate weight given to research studies based on their strengths and
      limitations. Only then can treatment standards that are effective against
      methicillin-resistant Staphylococcus aureus be adopted or refuted.

PMID- 22874135
TI  - Duty-cycled radiofrequency pulmonary vein isolation: an epic journey between
      enthusiasm and aversion.

PMID- 22874136
TI  - The landscape for epigenetic/epigenomic biomedical resources.
AB  - Recent advances in molecular biology and computational power have seen the
      biomedical sector enter a new era, with corresponding development of
      Bioinformatics as a major discipline. Generation of enormous amounts of data has
      driven the need for more advanced storage solutions and shared access through a
      range of public repositories. The number of such biomedical resources is
      increasing constantly and mining these large and diverse data sets continues to
      present real challenges. This paper attempts a general overview of currently
      available resources, together with remarks on their data mining and analysis
      capabilities. Of interest here is the recent shift in focus from genetic to
      epigenetic/epigenomic research and the emergence and extension of resource
      provision to support this both at local and global scale. Biomedical text and
      numerical data mining are both considered, the first dealing with automated
      methods for analyzing research content and information extraction, and the second
      (broadly) with pattern recognition and prediction. Any summary and selection of
      resources is inherently limited, given the spectrum available, but the aim is to
      provide a guideline for the assessment and comparison of currently available
      provision, particularly as this relates to epigenetics/epigenomics.

PMID- 22874137
TI  - Myocardial systolic and diastolic performance derived by 2-dimensional speckle
      tracking echocardiography in heart failure with normal left ventricular ejection
      fraction.
AB  - BACKGROUND: The aim of this study was to investigate the myocardial systolic and
      diastolic performance of the left ventricle (LV) in patients with heart failure
      with normal LV ejection fraction (HFNEF) through novel LV myocardial indices,
      which assess the systolic and diastolic function of the whole myocardium of the
      LV. METHODS AND RESULTS: LV myocardial systolic and diastolic performance were
      assessed as the average value of peak systolic strain and peak early-diastolic
      strain rate, respectively, in longitudinal, circumferential, and radial
      directions from all LV segments using 2-dimensional speckle-tracking
      echocardiography. We studied patients with HFNEF and a control group consisting
      of asymptomatic subjects with LV diastolic dysfunction of similar age, sex, and
      LV ejection fraction. A total of 322 patients were included (92 with HFNEF and
      230 with asymptomatic LV diastolic dysfunction). Myocardial systolic and
      diastolic LV performance were significantly lower in HFNEF (20.13+/-6.02% and
      1.14+/-0.27 s(-1)) than in patients with asymptomatic LV diastolic dysfunction
      (25.33+/-6.06% and 1.37+/-0.33 s(-1), respectively; all P<0.0001). In addition,
      patients with HFNEF with low systolic and diastolic LV myocardial performance had
      significantly higher LV filling pressures (17.1+/-6.6 and 17.6+/-6.3 versus
      12.0+/-5.1 and 11.7+/-4.7, respectively; all P<0.001) and lower cardiac output
      (4.8+/-1.0 L/min and 4.9+/-1.1 L/min versus 5.7+/-1.2 L/min and 5.8+/-1.1 L/min,
      respectively; all P<0.001) than patients with normal LV myocardial performance.
      In relation to these findings, the symptomatic status (ie, New York Heart
      Association functional class) was significantly altered in those patients with
      low systolic and diastolic LV myocardial performance. CONCLUSIONS: In patients
      with HFNEF, both systolic and diastolic LV myocardial performance are impaired,
      which is associated with increased LV filling pressures, decreased cardiac
      output, and worse New York Heart Association functional class. Therefore, the
      measurement of these myocardial parameters could be of great importance in HFNEF
      because these echocardiographic indices assess the multidirectional function of
      the whole myocardium of the LV, thereby allowing detection of an alteration of
      the global function of the LV which is associated with a worse symptomatic status
      in these patients.

PMID- 22874138
TI  - Food fortification improves the intake of all fortified nutrients, but fails to
      meet the estimated dietary requirements for vitamins A and B6, riboflavin and
      zinc, in lactating South African women.
AB  - OBJECTIVE: To investigate the impact of fortification by comparing food records
      and selected biochemical indicators of nutritional status pre- and post
      fortification. DESIGN: Mean intake from 24 h recalls (n 142) was compared with
      the Estimated Average Requirement (EAR) to determine the proportion with
      inadequate intake. In a subsample (n 34), diet and serum retinol, folate,
      ferritin and Zn were compared pre- and post-fortification for fortified nutrients
      vitamin A, thiamin, riboflavin, niacin, folic acid, Fe and Zn. SETTING: South
      Africa. SUBJECTS: Breast-feeding women (ninety-four HIV-infected, forty eight HIV
      uninfected) measured at ~6, 14, 24 weeks, and 9 and 12 months postpartum.
      RESULTS: Pre-fortification, >80 % of women did not meet the EAR for vitamins A,
      C, D, thiamin, riboflavin, niacin, B6, B12 and folate and minerals Zn, iodine and
      Ca. Dietary intake post-fortification increased for all fortified nutrients. In
      post-fortification food records, >70 % did not meet the EAR for Zn and vitamins
      A, riboflavin and B6. Serum folate and Zn increased significantly post
      fortification (P < 0.001 for both), with no change in ferritin and a reduction in
      retinol. Post-fortification marginal/deficient folate status was reduced (73.5 %
      pre v. 3.0 % post; P < 0.001), as was Zn deficiency (26.5 % pre v. 5.9 % post; P
      < 0.05). Pre- and post-fortification, >93 % were retinol replete. There was no
      change in Fe deficiency (16.7 % pre v. 19.4 % post; P = 0.728). CONCLUSIONS:
      Micronutrient intake improved with fortification, but >70 % of lactating women
      did not meet the EAR for Zn, vitamins A, riboflavin and B6. Although 100 %
      exceeded the EAR for Fe after fortification, Fe status did not improve.

PMID- 22874139
TI  - Clinical characteristics and causes of chest pain in 380 children referred to a
      paediatric cardiology unit.
AB  - BACKGROUND: Chest pain is a common presenting complaint to paediatrics,
      paediatric cardiology, and paediatric emergency departments. In this study, we
      prospectively evaluated clinical characteristics and causes of chest pain in
      children referred to our paediatric cardiology unit. METHODS: A total of 380
      children were included. Associated symptoms and past and family histories were
      evaluated. All patients underwent physical examination. The following studies
      were performed: complete blood count in all patients; fasting lipid profiles in
      overweight and obese children and children with a family history of premature
      cardiovascular disease; and electrocardiogram, chest X-ray, and echocardiogram in
      all patients. If necessary, 24-hour electrocardiogram monitoring or exercise
      stress tests were performed. Patients with a history of positive psychological
      findings were evaluated by a child psychiatrist. RESULTS: The most common causes
      of chest pain were musculoskeletal disorders (37.1%), idiopathic chest pain
      (29.2%), and miscellaneous disorders, for example precordial catch syndrome
      (15%), respectively. Only 1 of 380 (0.3%) patients had chest pain due to a
      cardiac disorder. Electrocardiograms were abnormal in 4 of 380 (1.1%) patients. A
      total of 9 of 380 patients (2.3%) had dyslipidaemia. CONCLUSIONS: Although a
      paediatric cardiology referral may provide reassurance to the primary care and
      emergency department physicians, our results show that cardiac aetiologies for
      paediatric chest pain are very rare. We think that many patients in our study
      were adequately evaluated only by careful history, and physical examination.
      Therefore, we suggest that it may not be necessary to use echocardiogram in the
      routine evaluation of children with chest pain.

PMID- 22874141
TI  - Challenges of the e-Health curricular education in bio-medical engineering and in
      medicine.
AB  - Curricular recommendations coming from highly respectable associations are highly
      useful. Nevertheless, they show fatigue in keeping the pace of any fast
      evolution, as in the ICT happens. So we do the attempt to disclose the emerging
      challenges affecting e-Health curricular education.

PMID- 22874142
TI  - Personal health records.
AB  - The paper addresses the complex interplay between patients, healthcare
      professionals, and technology in relation to the treatment of chronic patients.
      It reflects on an ongoing interdisciplinary action research project striving to
      design and implement IT support for communication and collaboration in the
      distributed heterogeneous network of chronic patients and the healthcare
      professionals that take care of them. An interactive personal health record (PHR)
      has been designed as part of the project. As such it is part of a trend to find
      ways to include patients in their own care process. This has been motivated by
      expected health benefits for the patients as well as promises to lead to reduced
      costs for a burdened healthcare system.

PMID- 22874143
TI  - Enhancing service delivering, improving quality of life, preserving independence
      through assistive technology.
AB  - In nowadays aging society, many people require assistance for activity of daily
      living. In most cases technologies have the potential to improve the quality of
      life for the older and disabled. We show how the use of a robotic platform with
      some embedded intelligence, the i-Walker, can help to improve the performance of
      the post-stroke individuals' rehabilitation.

PMID- 22874144
TI  - The future of biomedical informatics: a perspective from academia.
AB  - Academic biomedical informatics has achieved great successes through research
      contributions over several decades, now reflected in a thriving commercial
      marketplace for electronic health records and other informatics tools. That very
      success, coupled with changes in the ability of governments to support research
      at past levels, is forcing a reconsideration of the directions and emphases for
      faculty members in informatics academic units. This paper discusses those forces
      and proposes areas of emphasis that will strengthen the academic discipline as it
      evolves in the years ahead. The focus is on the role of academic informaticians
      as practitioners of informatics, as researchers, and as educators.

PMID- 22874145
TI  - Improving quality of life through eHealth - the patient perspective.
AB  - Patients have moved away from being passive recipients of care. They require
      access to their own health data, shared decision making and control over their
      care pathways. eHealth offers the tools to meet these requirements and to support
      both patients and care providers. However, opinions diverge in how far a patient
      provider partnership should be supported or full consumer autonomy be provided
      and there is still not enough evidence on how to design and implement effective
      eHealth solutions that create patient benefits. In this keynote paper different
      perspectives on the patient empowerment process, outcome measurement and eHealth
      development will be discussed as well as ongoing developments in the field of e
      citizen services be presented.

PMID- 22874147
TI  - Conceptual modeling for Prospective Health Technology Assessment.
AB  - Prospective Health Technology Assessment (ProHTA) is a new and innovative
      approach to analyze and assess new technologies, methods and procedures in health
      care. Simulation processes are used to model innovations before the cost
      intensive design and development phase. Thus effects on patient care, the health
      care system as well as health economics aspects can be estimated. To generate
      simulation models a valid information base is necessary and therefore conceptual
      modeling is most suitable. Project-specifically improved methods and
      characteristics of simulation modeling are combined in the ProHTA Conceptual
      Modeling Process and initially implemented for acute ischemic stroke treatment in
      Germany. Additionally the project aims at simulation of other diseases and health
      care systems as well. ProHTA is an interdisciplinary research project within the
      Cluster of Excellence for Medical Technology - Medical Valley European
      Metropolitan Region Nuremberg (EMN), which is funded by the German Federal
      Ministry of Education and Research (BMBF), project grant No. 01EX1013B.

PMID- 22874148
TI  - Data Definition Ontology for clinical data integration and querying.
AB  - This paper describes an approach to build a Data Definition Ontology (DDO) in the
      context of full domain ontology integration with datasets in order to share and
      query clinical heterogeneous data repositories. We have adapted an existing
      semantic web tool (D2RQ) to implement a process that automatically generates the
      DDO from a database information model, thanks to reverse engineering and schema
      mapping approaches. This study has been performed in the context of the DebugIT
      European project (Detecting and Eliminating Bacteria UsinG Information
      Technology) that aims to control and monitor the bacterial growth via a semantic
      interoperability platform (IP). The evaluation of the process is based, first, on
      the accuracy of the produced DDO for different samples of database storage and
      second, by checking the congruency between the DDO and the D2RQ database mapping
      file.

PMID- 22874149
TI  - Migration path for structured documentation systems including standardized
      medical device data.
AB  - A standardized end-to-end solution has been implemented with the aim of
      supporting the semantic integration of clinical content in institution spanning
      applications. The approach outlined is a proof-of-concept design. It has shown
      that the standards chosen are suitable to integrate device data into forms, to
      document the results consistently and finally enable semantic interoperability.
      In detail the implementation includes a standardized device interface, a
      standardized representation of data entry forms and enables the communication of
      structured data via HL7 CDA. Because the proposed method applies a combination of
      standards semantic interoperability and the possibility of a contextual
      interpretation at each stage can be ensured.

PMID- 22874150
TI  - Quality requirements for EHR archetypes.
AB  - The realisation of semantic interoperability, in which any EHR data may be
      communicated between heterogeneous systems and fully understood by computers as
      well as people on receipt, is a challenging goal. Despite the use of standardised
      generic models for the EHR and standard terminology systems, too much optionality
      and variability exists in how particular clinical entries may be represented.
      Clinical archetypes provide a means of defining how generic models should be
      shaped and bound to terminology for specific kinds of clinical data. However,
      these will only contribute to semantic interoperability if libraries of
      archetypes can be built up consistently. This requires the establishment of
      design principles, editorial and governance policies, and further research to
      develop ways for archetype authors to structure clinical data and to use
      terminology consistently. Drawing on several years of work within communities of
      practice developing archetypes and implementing systems from them, this paper
      presents quality requirements for the development of archetypes. Clinical
      engagement on a wide scale is also needed to help grow libraries of good quality
      archetypes that can be certified. Vendor and eHealth programme engagement is
      needed to validate such archetypes and achieve safe, meaningful exchange of EHR
      data between systems.

PMID- 22874151
TI  - Using archetypes for defining CDA templates.
AB  - While HL7 CDA is a widely adopted standard for the documentation of clinical
      information, the archetype approach proposed by CEN/ISO 13606 and openEHR is
      gaining recognition as a means of describing domain models and medical knowledge.
      This paper describes our efforts in combining both standards. Using archetypes as
      an alternative for defining CDA templates permit new possibilities all based on
      the formal nature of archetypes and their ability to merge into the same artifact
      medical knowledge and technical requirements for semantic interoperability of
      electronic health records. We describe the process followed for the normalization
      of existing legacy data in a hospital environment, from the importation of the
      HL7 CDA model into an archetype editor, the definition of CDA archetypes and the
      application of those archetypes to obtain normalized CDA data instances.

PMID- 22874152
TI  - Using enterprise ontology for improving emergency management in hospitals.
AB  - In a competitive world, healthcare organizations are forced to make improvements
      in order to compete and prosper. Healthcare services suffer from lack of change
      and inefficiency, which affects the delivery of sustainable services. We propose
      a method based on DEMO to find non value-added transactions that must be
      redesigned to simplify processes. This methodology was chosen as a basis for our
      solution because it provides a better understanding of the dynamics of an
      organization, has a strong and well-formed theory, and allows a good alignment
      between the enterprise design and operation. A demonstration of the method was
      accomplished in an emergency department, making it possible to find transactions
      that can be improved or automated. To evaluate the results we used interviews,
      Moody and Shanks Quality Framework, and the Four Principles from Osterle et al.,
      which shows that the method yields an adequate and clear process view and is
      reliable when it comes to improving healthcare operational processes.

PMID- 22874153
TI  - A ClaML-based interface for the import of monohierarchical classifications.
AB  - The relevance of controlled vocabularies in promoting the standardized
      representation and exchange of clinical data is no longer to be proved. As part
      of a national project we evaluated the integration of classifications and
      terminologies in metadata registries based on the standard ISO/IEC 11179
      Information technology - Metadata Registries (MDR). To overcome integration and
      maintenance tasks of monohierarchical classifications in the MDR, and to provide
      an exchange format between classifications publishers and the MDR, we implemented
      an import interface based on the Classification Markup Language (ClaML). The
      implementation transforms classifications from ClaML into a MDR conform structure
      using the Extensible Stylesheet Language Transformation (XSLT). Several XSLT
      scripts were linked and successively executed. The national obliged
      classifications ICD-10-GM and OPS could be hence imported into the MDR. Problems
      arose with different interpretations and extensions of ClaML by WHO and the
      national publisher. We therefore advocate a unique interpretation of ClaML as
      prerequisite for a general use of the ClaML import interface.

PMID- 22874154
TI  - An information artifact ontology perspective on data collections and associated
      representational artifacts.
AB  - Biomedical data collections are typically compiled on the basis of assessment
      instruments and associated terminologies and their data structure explained by
      means of data dictionaries. The Information Artifact Ontology (IAO) is an attempt
      to give a realism-based account of the essence of information entities and how
      components of such entities relate to each other and to that what they are
      information about. Changes in the taxonomy and the definitions of the IAO, most
      importantly the addition of the terms 'representational artifact' and
      'representational unit', are proposed to make the IAO a useful tool to clarify
      formally the distinctions and commonalities between data collections and
      associated artifacts that are compiled independently from each other, yet cover
      the same domain.

PMID- 22874155
TI  - Automatic generation of MedDRA terms groupings using an ontology.
AB  - In the context of PROTECT European project, we have developed an ontology of
      adverse drug reactions (OntoADR) based on the original MedDRA hierarchy and a
      query-based method to achieve automatic MedDRA terms groupings for improving
      pharmacovigilance signal detection. Those groupings were evaluated against
      standard handmade MedDRA groupings corresponding to first priority
      pharmacovigilance safety topics. Our results demonstrate that this automatic
      method allows catching most of the terms present in the reference groupings, and
      suggest that it could offer an important saving of time for the achievement of
      pharmacovigilance groupings. This paper describes the theoretical context of this
      work, the evaluation methodology, and presents the principal results.

PMID- 22874156
TI  - Formal specification of an ontology-based service for EHR interoperability.
AB  - OBJECTIVE: The objective of this paper is to describe by a Platform Independent
      Model, the formal specification of an ontology-based service for electronic
      health records interoperability. METHODS: The GCM is used as a framework for the
      service's architectural design. The formal specification of the service is an
      extension of the OMG CTS 2 specification. A review of mapping approaches is also
      provided. RESULTS: The paper describes the service' information and computation
      models, including the mapping process workflow. The platform specific
      implementation (Platform Specific Model) is provided as a set of WSDL interfaces.
      The specification includes ontology mapping algorithms and tools needed.

PMID- 22874157
TI  - Mapping SNOMED CT to ICD-10.
AB  - A collaboration between the International Health Terminology Standards
      Development Organisation (IHTSDO(r)) and the World Health Organization (WHO) has
      resulted in a priority set of cross maps from SNOMED CT(r) to ICD-10(r) to
      support the epidemiological, statistical and administrative reporting needs of
      the IHTSDO member countries, WHO Collaborating Centres, and other interested
      parties. Overseen by the Joint Advisory Group (JAG), approximately 20,000 SNOMED
      CT concepts have been mapped to ICD-10 using a stand-alone mapping tool. The
      IHTSDO Map Special Interest Group (MapSIG) developed the mapping heuristics and
      established the validation process in conjunction with the JAG. Mapping team
      personnel were selected and then required to participate in a training session
      using the heuristics and tool. Quality metrics were used to assess the training
      program. An independent validation of cross map content was conducted under the
      supervision of the American Health Information Management Association. Lessons
      learned are being incorporated into the plans to complete the mapping of the
      remaining SNOMED CT concepts to ICD-10.

PMID- 22874158
TI  - Rare diseases knowledge management: the contribution of proximity measurements in
      OntoOrpha and OMIM.
AB  - In this paper, we introduce an application of Proxima and define a new measure of
      proximity between two concepts present in an ontology. The approach is based on
      the three dimensions of a conceptualization: intention with relations between
      concepts, expression with terms denoting concepts, and extension with instances
      of concepts. This preliminary work, in the field of rare diseases, involved the
      Orphanet Ontology of Rare Diseases (OntoOrpha) and corpus of texts extracted from
      Online Inheritance in Man (OMIM). The proximity measurements are consistent with
      an appropriate representation of groups of diseases in the ontology, which are
      derived from the Orphanet classifications of rare diseases. Other semantic
      relations are explored and new perspectives in medical knowledge curation are
      proposed.

PMID- 22874159
TI  - Design of an original interface that facilitates the use of clinical practice
      guidelines of infection by physicians in primary care.
AB  - Increasing physician adherence to the clinical practice guidelines (CPG) for
      infections should improve antibiotic prescription practices. The aim of this
      study was to present the decision elements of these CPG in an original interface
      to be implemented in the website "Antibiocarte". We manually analyzed all CPG
      available for ambulatory treatment of infections. We extracted all terms related
      to the antibiotic therapy decisions and grouped them into decision or action
      variables. We then modeled the antibiotic therapy decision process and designed
      an interface according to ergonomic principles. The interface consists of five
      fixed parts: a decision table, two information zones, a zone with the reasons for
      hospitalization, and a zone with situations not concerned by the CPG. All CPG
      could be implemented according to this model. The usability of the new interface
      was evaluated by ten general practitioners using the System Usability Scale (SUS)
      and found to be satisfactory and appropriate for clinical use.

PMID- 22874160
TI  - Knowledge representation for fuzzy inference aided medical image interpretation.
AB  - Knowledge defines how an automated system transforms data into information. This
      paper suggests a representation method of medical imaging knowledge using fuzzy
      inference systems coded in XML files. The imaging knowledge incorporates features
      of the investigated objects in linguistic form and inference rules that can
      transform the linguistic data into information about a possible diagnosis. A
      fuzzy inference system is used to model the vagueness of the linguistic medical
      imaging terms. XML files are used to facilitate easy manipulation and deployment
      of the knowledge into the imaging software. Preliminary results are presented.

PMID- 22874161
TI  - MRI image artifact ontology: a proposed method for improved recognition.
AB  - Magnetic Resonance Imaging is an essential diagnostic imaging technique. The
      complexity of interpreting MRI images is often compounded by the presence of a
      wide range of artifacts which are often challenging to identify and eliminate.
      Ontology permits the construction of a knowledge database with which users can
      interact given an appropriate interface. The goal of this work is to create an
      interactive tool for the ontology of MRI artifacts that will allow a radiologist
      to compare any given MRI artifact image with those contained in the ontology.
      MATERIAL AND METHOD: Using Protege 4, we have constructed the ontology with input
      from an expert in MRI artifacts and utilizing images exemplifying such artifacts.
      The graphical user interface has been built in Java and the linkage with the
      ontology made with Owl API. RESULTS: Using the tool, users can compare imaging
      artifacts encountered in daily practice to those in the database. Once a user has
      identified the image the most similar to their own, they then have instantaneous
      access to the knowledge contained in the ontology about the artifact. Individual
      users can also submit images and have access to DICOM data.

PMID- 22874162
TI  - Ontology driven decision support systems for medical diagnosis - an interactive
      form for consultation in patients with plasma cell disease.
AB  - Multiple myeloma (MM) is a malignant disorder characterized by the monoclonal
      proliferation of B cell derived plasma cells in the bone marrow. The diagnosis
      depends on the identification of abnormal monoclonal marrow plasma cells,
      monoclonal protein in the serum or urine, evidence of end-organ damage, and a
      clinical picture consistent with MM. The distinction between MM stages-
      monoclonal gammopathy of undetermined significance or indolent myeloma-is
      critical in guiding therapy. This paper describes how to produce ontology-driven
      semiological rules base (SRB) and a consultation form to aid in the diagnosis of
      plasma cells diseases. We have extracted the MM sub-ontology from the NCI
      Thesaurus. Using Protege 3.4.2 and owl1, criteria in the literature for the
      diagnosis and staging of MM have been added to the ontology. All quantitative
      parameters have been transformed to a qualitative format. A formal description of
      MM variants and stages has been given. The obtained ontology has been checked by
      a reasoner and instantiated to obtain a SRB. The form created has been tested and
      evaluated utilizing 63 clinical medical reports. The likelihood for a disease
      being the correct diagnosis is determined by computing a ratio. The resulting
      tool is relevant for MM diagnosis and staging.

PMID- 22874163
TI  - The reproducibility of CLIF, a method for clinical quality indicator
      formalisation.
AB  - In order to be able to automatically calculate clinical quality indicators, we
      have proposed CLIF, a stepwise method for clinical quality indicator
      formalisation. Quality indicators are used for external accountability and
      hospital comparison. As clinical quality indicators are computed in a
      decentralised manner by the hospitals themselves, reproducibility of the
      formalisation method is essential to ensure the comparability of calculated
      values. Thus, we performed a case study to investigate the reproducibility of
      CLIF. Eight participants formalised the same sample quality indicator with the
      help of a web-based indicator-authoring tool that facilitates the application of
      CLIF. We analysed the results per step and concluded that the method itself leads
      to reproducible results. To further improve reproducibility, ambiguities in the
      indicator text must be clarified and trained experts are needed to encode
      clinical concepts and to specify the relations between concepts.

PMID- 22874164
TI  - Virtual medical record implementation for enhancing clinical decision support.
AB  - Development of clinical decision support systems (CDS) is a process which highly
      depends on the local databases, this resulting in low interoperability. To
      increase the interoperability of CDS a standard representation of clinical
      information is needed. The paper suggests a CDS architecture which integrates
      several HL7 standards and the new vMR (virtual Medical Record). The clinical
      information for the CDS systems (the vMR) is represented with Topic Maps
      technology. Beside the implementation of the vMR, the architecture integrates: a
      Data Manager, an interface, a decision making system (based on Egadss), a
      retrieving data module. Conclusions are issued.

PMID- 22874165
TI  - An application of symbolic dynamics for FHRV assessment.
AB  - Fetal heart rate variability is surely one of the most important parameters to
      monitor fetal wellbeing. Linear studies, widely employed to study fetal heart
      variability and its correlations with the development of the autonomous nervous
      system, have shown some limitations in highlight dynamics potentially relevant.
      During the last decades, therefore, nonlinear analysis methods have gained a
      growing interest to analyze the chaotic nature of cardiac activity. Techniques
      investigating nonlinear dynamics have been already successfully employed in
      adults, to analyze different physiological and pathological states. Concerning
      fetal monitoring, instead, a smaller number of papers is available in the
      literature; even if symbolic dynamics was recently employed to quantify fetal
      heart rate regularity, demonstrating that the use of this technique may lead to a
      better and more differentiated understanding of normal fetal physiological
      development. In this work, we applied the symbolic dynamics to analyze fetal
      heart rate variability in healthy fetuses at the end of a physiological
      pregnancy. Our results confirmed the potentiality of the technique to highlight
      differences between signals characterized by more or less variability.

PMID- 22874166
TI  - Automated versus interactive spectral analysis of heart rate variability from 24
      hour Holter recordings in heart failure patients.
AB  - Accurate spectral analysis of 24-hour heart rate variability (HRV) requires time
      consuming interactive control of the overall processing, limiting its feasibility
      in large scale clinical trials. Fully automatic procedures allow a dramatic
      reduction of analysis time but the level of accuracy loss is unknown. In this
      study we compared automatic and interactive measurements of HRV indexes in a
      sample of 246 Holter recordings from chronic heart failure patients. We measured
      the total power of HRV and the power in the very low (0.01-0.04 Hz), low (0.04
      0.15 Hz) and high (0.15-0.4 Hz) frequency bands. The comparison between the two
      methods was performed by computing the normalized difference between automatic
      and interactive measurements and estimating the bias and 95% limits of agreement.
      Automatic measurements showed a small bias (< +/-8%) compared to interactive
      measurements, while the limits of agreement were <=+/-23% in all spectral
      indexes. Our results indicate that the systematic and random difference between
      automatic and interactive measurements of spectral indexes of HRV are acceptable
      for clinical studies.

PMID- 22874167
TI  - Probabilistic graphical models for effective connectivity extraction in the brain
      using FMRI data.
AB  - In this study using Bayesian network method to learn the structure of effective
      connectivity among brain regions involved in a functional MRI. The approach is
      exploratory in the sense that it does not require a priori model as in the
      earlier approaches, such as the Structural Equation Modeling or Dynamic Causal
      Modeling, which can only affirm or refute the connectivity of a previously known
      anatomical model or a hypothesized model. The conditional probabilities that
      render the interactions among brain regions in Bayesian networks represent the
      connectivity in the complete statistical sense. This method is applicable even
      when the number of regions involved in the cognitive network is large or unknown.
      In this study, we demonstrated the present approach using synthetic data and fMRI
      data collected in attention to motion in the visual system task.

PMID- 22874168
TI  - Scale-space methods for live processing of sensor data.
AB  - A temporal scale-space is a vector space spanned by time and a scale parameter,
      and by constructing the scale-space correctly a causal structure can be imposed
      on the scale-space. This enables early warning of significant changes in sensor
      data at an early time, and on any scale. We describe a feasibility study on how
      to use these ideas for live surveillance of monitoring processes such that
      important features can be visualized and users warned about changes an early
      stage. Sensor data from motion sensors on patients with chronic obstructive
      pulmonary disease are used as the example of such system, where important pattern
      are found and visualized using significance plots.

PMID- 22874169
TI  - Segmentation of Crohn, Lymphangiectasia, Xanthoma, Lymphoid hyperplasia and
      Stenosis diseases in WCE.
AB  - Wireless capsule endoscopy (WCE) is a great breakthrough for Gastrointestinal
      (GI) Tract diagnoses which can view the entire gastrointestinal tract, especially
      the small bowel, without invasiveness and sedation. However, a tough problem
      associated with this new device is that too many images to be inspected by naked
      eyes is difficult for physicians, Thus it is essential to find an automatic and
      intelligent diagnosis method to help physicians. In this paper, a new
      segmentation algorithm for detection of Lymphangiectasia, Xanthoma, Crohn, and
      Stenosis in WCE images is proposed. This new approach mainly uses the HSV color
      space, sigmoid function and canny edge detector. We compare our method with a
      fuzzy c-mean clustering. We show that sensitivities of the sigmoid function for
      Lymphangiectasia, Lymphoid hyperplasia, severe Crohn's disease, Xanthoma and
      ulcerated Stenosis are respectively 89.32%, 91.27%, 95.45%, 87.01%, 97% and
      sensitivities of the fuzzy c-means clustering with same order are 83.91%, 86.7%,
      96.38%, 90.4%, 93.83%. Totally, the sigmoid function is more specific and
      sensitive, with same accuracy.

PMID- 22874171
TI  - Customization of biomedical terminologies.
AB  - Within the biomedical area over one hundred terminologies exist and are merged in
      the Unified Medical Language System Metathesaurus, which gives over 1 million
      concepts. When such huge terminological resources are available, the users must
      deal with them and specifically they must deal with irrelevant parts of these
      terminologies. We propose to exploit seed terms and semantic distance algorithms
      in order to customize the terminologies and to limit within them a semantically
      homogeneous space. An evaluation performed by a medical expert indicates that the
      proposed approach is relevant for the customization of terminologies and that the
      extracted terms are mostly relevant to the seeds. It also indicates that
      different algorithms provide with similar or identical results within a given
      terminology. The difference is due to the terminologies exploited. A special
      attention must be paid to the definition of optimal association between the
      semantic similarity algorithms and the thresholds specific to a given
      terminology.

PMID- 22874170
TI  - Generation of a probabilistic arterial cerebrovascular atlas derived from 700
      time-of-flight MRA datasets.
AB  - The cerebral vasculature is a complex vessel network with high variations among
      human subjects. Although the coarse structure and spatial relationships of the
      main cerebrovascular branches are well known, not much knowledge about inter
      individual vessel variability of humans at a finer level is available. The aim of
      this work is to present a probabilistic atlas of cerebral arterial vascular
      structures derived from 700 Time-of-Flight (TOF) magnetic resonance angiography
      (MRA) datasets of healthy subjects. Therefore, the cerebrovascular system was
      automatically segmented in each TOF datasets. In a following step, each TOF
      dataset and corresponding segmentation was registered to the MNI brain atlas. The
      registered datasets were then used for generation of a probabilistic
      cerebrovascular atlas. The generated atlas was evaluated with respect to three
      possible applications. The results suggest that the atlas is especially helpful
      to obtain knowledge about the cerebrovascular anatomy and its variations in terms
      of vessel occurrence probability. Furthermore, it appears useful for
      initialization of automatic cerebrovascular segmentation methods while an
      application for detection of vessel pathologies seems only feasible for large
      malformations.

PMID- 22874172
TI  - IRMA Code II: unique annotation of medical images for access and retrieval.
AB  - Content-based image retrieval (CBIR) provides novel options to access large
      repositories of medical images, in particular for storing, querying and
      reporting. This requires a revisit of nomenclatures for image classification such
      as DICOM, SNOMED, and RadLex. For instance, DICOM defines only about 20 concept
      terms for body regions, which partly overlap. This is insufficient to access the
      visual image characteristics. In 2002, the Image Retrieval in Medical
      Applications (IRMA) project proposed a mono-hierarchic, multi-axial coding scheme
      called IRMA Code. It was used in the Cross Language Evaluation Forum (ImageCLEF)
      annotation tasks. Ten years of experience have discovered several weak points. In
      this paper, we propose eight axes of three levels in hierarchy for (A) anatomy,
      (B) biological system, (C) configuration, (D) direction, (E) equipment, (F)
      finding, (G) generation, and (H) human maneuver as well as additional flags for
      age class, body side, contrast agent, ethnicity, finding certainty, gender,
      quality, and scanned film, which are captured in form of another axis (I). Using
      a tag-based notation IRMA Code II supports multiple selection coding within one
      axis, which is required for the new main categories.

PMID- 22874173
TI  - Method for mapping the French CCAM terminology to the UMLS metathesaurus.
AB  - The French coding system of surgical procedures, the Classification Commune des
      Actes Medicaux (CCAM), is used in France for DRG databases and fee for services
      payment. Mapping between CCAM and other clinical procedures terminologies by the
      means of UMLS metathesaurus is essential in order to increase semantic
      interoperability between different healthcare terminologies and between different
      case mix systems. In a previous work the CISMeF team used an automatic approach
      to map CCAM descriptors to the French part of the UMLS metathesaurus. In another
      way for the French funded research project InterSTIS, we performed a mapping
      using MetaMap based on the top level semantic structure descriptors of anatomy
      and action of CCAM translated from French to English. This paper aims to present
      this new approach and to compare the results with the previous one. The
      combination of both approaches significantly improved the coverage of the mapping
      to 68 % for both descriptors and 95 % for at least one descriptor.

PMID- 22874174
TI  - Semantic relations of binary compounds annotated with SNOMED CT.
AB  - The objective of this paper is to investigate whether a meaningful interpretation
      can be easily assigned to compound medical terms that have been assigned two
      distinct concepts taken from one of the most comprehensive, clinical healthcare
      terminologies, the (Swedish) SNOMED CT(r). A binary compound term is a union of
      two terms to construct a complex term of special meaning that is quickly conveyed
      by not using separated (multiword) terms but rather solid or closed ones (not
      separated by space or hyphen). This is a case when the vocabulary lacks a single
      code for such concept; at the same time, solid compounds is the norm for
      expressing compounds in Germanic languages, such as Swedish. It is therefore
      useful and challenging to both identify such compounds and also determine the
      semantic relation that holds between the compound's constituents. The hypothesis
      we explore is that, if there are two or more noun compounds in which the head and
      modifier of each one belong to the same semantic type respectively, then the same
      relation probably holds in each of them. The juxtaposition of the concepts'
      membership within the SNOMED CT is used for determining an approximation of the
      semantic relation between head and modifier.

PMID- 22874175
TI  - The issue of building generative terminologies for automatic medical data
      aggregation.
AB  - This work addresses the problem of medical terminologies building. Starting from
      a set of elementary knowledge, a multi-hierarchical terminology is generated
      according to formal principles that are based on explicit classificatory points
      of view. The experimentation has been carried out on kidney diseases.
      Hierarchical conceptual structures are generated starting from Conceptual Graph
      based definition of kidney disease, a hierarchy of defining types and a set of
      organizing rules. The generated hierarchy includes new potential disease concepts
      with different level of likeliness. This "ready to use" generated multi
      hierarchical terminology can be used for coding, includes new potential terms for
      the future and, due to the formalization of classificatory principles, offers
      improved opportunities of diseases instances aggregation. These features are
      looking very promising in the context of epidemiological observation tools
      (registries, long term cohort studies). They offer mean to meet two critical
      requirements: the statistical continuity in data analysis and the sustainable
      management of the underlying terminological system.

PMID- 22874176
TI  - Towards a bilingual Alzheimer's disease terminology acquisition using a parallel
      corpus.
AB  - We present in this paper a method for acquiring a bilingual terminology
      concerning the Alzheimer's disease using a parallel corpus. NLP techniques are
      used for parsing English and French texts in order to extract candidate terms.
      These terms are then matched automatically using an approach that combines two
      alignment techniques: one based on the calculation of an association score
      between two terms, and another technique based on the calculation of
      morphological similarity. This method provided good results on an Alzheimer's
      disease related corpus with a precision of 73%.

PMID- 22874177
TI  - An ontological approach to manage and harmonize document types.
AB  - Working interoperability when consuming resources of different document types
      requires a harmonized understanding of their structures and contents. But
      sometimes, a specification has not made the underlying model explicit which would
      enable a coherent understanding. This paper analyses the commonly used structures
      of different document types and proposes an ontological structure resulting in
      the so-called Document Type Ontology (DTO). This solution is based on the Generic
      Component Model (GCM) as an architectural framework and the Communication
      Standards Ontology (CSO) and Basic Formal Ontology (BFO) presented earlier.

PMID- 22874178
TI  - Patient support ICT tool for hypertension monitoring.
AB  - Detection of hypertension is traditionally a matter for the general practitioner,
      but an alternative detection scheme is home blood pressure measurement by
      patients, on patients' or doctors' decision. We designed and implemented a
      prototype software tool to provide information about hypertension, video
      instructions on correct home blood pressure measurement technique and a
      measurements diary. The system was developed using standard, software development
      methods and techniques. The program was developed for Danish-speaking patients.
      Usability (navigability, level and outcome of instructions, logical arrangement,
      level and focus of information, and program accessibility) was evaluated in a
      think-aloud test with test users performing specific, realistic tasks. The
      prototype provides written information about hypertension, written and video
      instructions on correct blood pressure measurement technique, and measurements
      diary functionality. All test users performed all tasks and rated navigability,
      level and outcome of instructions, logical arrangement, level and focus of
      information, and program accessibility high, and had positive attitudes towards
      the system. The components in the patient support tool can be used separately or
      in combination. The effects of video for home blood pressure measurement
      technique instruction remain unexplored.

PMID- 22874179
TI  - RAVEL: retrieval and visualization in ELectronic health records.
AB  - Because of the ever-increasing amount of information in patients' EHRs,
      healthcare professionals may face difficulties for making diagnoses and/or
      therapeutic decisions. Moreover, patients may misunderstand their health status.
      These medical practitioners need effective tools to locate in real time relevant
      elements within the patients' EHR and visualize them according to synthetic and
      intuitive presentation models. The RAVEL project aims at achieving this goal by
      performing a high profile industrial research and development program on the EHR
      considering the following areas: (i) semantic indexing, (ii) information
      retrieval, and (iii) data visualization. The RAVEL project is expected to
      implement a generic, loosely coupled to data sources prototype so that it can be
      transposed into different university hospitals information systems.

PMID- 22874180
TI  - Standard based multiclient medical data visualization.
AB  - An efficient interaction between a doctor and an electronic health record (EHR)
      depends also on the visual layer of an EHR. As users with various backgrounds and
      needs have different perspectives on the same data visualization methods must be
      flexible to provide the optimal interface. The ISO 13606 community is interested
      in developing requirements on a generic visualization method that can supplement
      the archetype model. Our research aims at specifying the requirements on a
      medical data visualization method based on the ISO13606 data model. XML allows a
      clear structuring and validation of the data due to the built-in standard
      features. The proposed visual medical concept allows separating the medical
      knowledge from the visualization knowledge. The research is focused defining the
      optimal XML schema for a visual medical concept to allow multiclient generic data
      presentation.

PMID- 22874181
TI  - An advanced search engine for patent analytics in medicinal chemistry.
AB  - Patent collections contain an important amount of medical-related knowledge, but
      existing tools were reported to lack of useful functionalities. We present here
      the development of TWINC, an advanced search engine dedicated to patent retrieval
      in the domain of health and life sciences. Our tool embeds two search modes: an
      ad hoc search to retrieve relevant patents given a short query and a related
      patent search to retrieve similar patents given a patent. Both search modes rely
      on tuning experiments performed during several patent retrieval competitions.
      Moreover, TWINC is enhanced with interactive modules, such as chemical query
      expansion, which is of prior importance to cope with various ways of naming
      biomedical entities. While the related patent search showed promising
      performances, the ad-hoc search resulted in fairly contrasted results.
      Nonetheless, TWINC performed well during the Chemathlon task of the PatOlympics
      competition and experts appreciated its usability.

PMID- 22874182
TI  - Classification and prioritization of biomedical literature for the comparative
      toxicogenomics database.
AB  - We present a new approach to perform biomedical documents classification and
      prioritization for the Comparative Toxicogenomics Database (CTD). This approach
      is motivated by needs such as literature curation, in particular applied to the
      human health environment domain. The unique integration of chemical,
      genes/proteins and disease data in the biomedical literature may advance the
      identification of exposure and disease biomarkers, mechanisms of chemical
      actions, and the complex aetiologies of chronic diseases. Our approach aims to
      assist biomedical researchers when searching for relevant articles for CTD. The
      task is functionally defined as a binary classification task, where selected
      articles must also be ranked by order of relevance. We design a SVM classifier,
      which combines three main feature sets: an information retrieval system (EAGLi),
      a biomedical named-entity recognizer (MeSH term extraction), a gene normalization
      (GN) service (NormaGene) and an ad-hoc keyword recognizer for diseases and
      chemicals. The evaluation of the gene identification module was done on
      BioCreativeIII test data. Disease normalization is achieved with 95% precision
      and 93% of recall. The evaluation of the classification was done on the corpus
      provided by BioCreative organizers in 2012. The approach showed promising
      performance on the test data.

PMID- 22874183
TI  - CliniQA : highly reliable clinical question answering system.
AB  - Evidence-based medicine (EBM) aims to apply the best available evidences gained
      from scientific method to clinical decision making. From the computer science
      point of view, the current bottleneck of applying EBM by a decision maker (either
      a patient or a physician) is the time-consuming manual retrieval, appraisal, and
      interpretation of scientific evidences from large volume of and rapidly
      increasing medical research reports. Patients do not have the expertise to do it.
      For physicians, study has shown that they usually have insufficient time to
      conduct the task. CliniQA tries to shift the burden of time and expertise from
      the decision maker to the computer system. Given a single clinical foreground
      question, the CliniQA will return a highly reliable answer based on existing
      medical research reports. Besides this, the CliniQA will also return the analyzed
      information from the research report to help users appraise the medical evidences
      more efficiently.

PMID- 22874184
TI  - Development and representation of health indicators with thematic maps.
AB  - Italian Local Health Care Agencies (ASLs) have the role of managing the public
      healthcare resources in their area of competence. To this end, the ASL of Pavia
      has implemented a data warehouse, which collects and integrates health data of
      more than 500,000 people since 2004. We have exploited such data repository to
      compute a variety of yearly health indicators, which have been represented on
      thematic maps of the area. Thanks to a Web-based application, the ASL decision
      makers can monitor the area with a fine-grained spatial detail, dissecting the
      epidemiological, economical and pharmaceutical factors underlying citizens'
      health and patients' care. The implemented tool is currently up-and-running and
      has been evaluated with a usability questionnaire on a small number of users.

PMID- 22874185
TI  - Efficient medical information retrieval in encrypted Electronic Health Records.
AB  - The recent development of eHealth platforms across the world, whose main
      objective is to centralize patient's healthcare information to ensure the best
      continuity of care, requires the development of advanced tools and techniques for
      supporting health professionals in retrieving relevant information in this vast
      quantity of data. However, for preserving patient's privacy, some countries
      decided to de-identify and encrypt data contained in the shared Electronic Health
      Records, which reinforces the complexity of proposing efficient medical
      information retrieval approach. In this paper, we describe an original approach
      exploiting standards metadata as well as knowledge organizing systems to overcome
      the barriers of data encryption for improving the results of medical information
      retrieval in centralized and encrypted Electronic Health Records. This is done
      through the exploitation of semantic properties provided by knowledge organizing
      systems, which enable query expansion. Furthermore, we provide an overview of the
      approach together with illustrating examples and a discussion on the advantages
      and limitations of the provided framework.

PMID- 22874186
TI  - The use of linked registries to assess long-term mortality of ICU patients.
AB  - Clinical registries are frequently used to monitor and analyze the quality of
      health care by assessing the in-hospital mortality. However, long-term mortality
      is often ignored as it is rarely recorded in such clinical registries. In this
      study linkage of a clinical registry and administrative database is used to
      assess the longterm mortality of a large ICU sample. Information about long-term
      mortality may be used to inform patients about their prognosis, to get insight in
      factors that influence long-term mortality, and to adjust admission policy to the
      ICU. This study showed that the observed mortality in the total ICU population at
      3, 6, and 12 months after ICU admission was 20.3%, 22.9%, and 26.6% respectively.
      Medical and urgent surgery patients showed a higher long-term mortality risk and
      planned surgery patients showed a lower long-term mortality risk compared to the
      other ICU patients. In this study we have focused on the general ICU population,
      though linkage of clinical and administrative databases can also be used to
      perform analyses in specific diagnostic ICU populations or for non-ICU patients.
      In this study 71.4% of the clinical records could be linked with the
      administrative database. Future studies should focus on improving linkage of
      different registries.

PMID- 22874187
TI  - Grouping the pharmacovigilance terms with a hybrid approach.
AB  - Pharmacovigilance is the activity related to the collection, analysis and
      prevention of adverse drug reactions (ADRs) induced by drugs. It leads to the
      safety survey of pharmaceutical products. The pharmacovigilance process benefits
      from the traditional statistical approaches and also from the qualitative
      information on semantic relations between close ADR terms, such as SMQs or
      hierarchical levels of MedDRA. In this work, our objective is to detect the
      semantic relatedness between the ADR MedDRA terms. To achieve this, we combine
      two approaches: semantic similarity algorithms computed within structured
      resources and terminology structuring methods applied to a raw list of the MedDRA
      terms. We compare these methods between them and study their differences and
      complementarity. The results are evaluated against the gold standard manually
      compiled within the pharmacovigilance area and also with an expert. The
      combination of the methods leads to an improved recall.

PMID- 22874188
TI  - Information extraction from SMS text related to a reminder service for
      outpatients.
AB  - This work evaluates the users' satisfaction with an SMS-based reminder system
      that is being used since about six years by an Italian healthcare organization.
      The system was implemented for reducing dropouts. This goal has been achieved, as
      dropout decreased from 8% to 4%. During these years, a number of reminded
      citizens, even not required, sent an SMS message back, with comments about the
      service, further requirements, etc. We collected some thousands of them. Their
      analysis may represent a useful feedback to the healthcare organization. We used
      conditional random fields as the information extraction method for classifying
      messages into appreciation, critique, inappropriateness, etc. The classification
      system achieved a very good overall performance (F1-measure of 94%), thus it can
      be used from here on to monitor the users' satisfaction in time.

PMID- 22874190
TI  - Linguistic analysis of large-scale medical incident reports for patient safety.
AB  - The analysis of medical incident reports is indispensable for patient safety. The
      cycles between analysis of incident reports and proposals to medical staffs are a
      key point for improving the patient safety in the hospital. Most incident reports
      are composed from freely written descriptions, but an analysis of such free
      descriptions is not sufficient in the medical field. In this study, we aim to
      accumulate and reinterpret findings using structured incident information, to
      clarify improvements that should be made to solve the root cause of the accident,
      and to ensure safe medical treatment through such improvements. We employ natural
      language processing (NLP) and network analysis to identify effective categories
      of medical incident reports. Network analysis can find various relationships that
      are not only direct but also indirect. In addition, we compare bottom-up results
      obtained by NLP with existing categories based on experts' judgment. By the
      bottom-up analysis, the class of patient managements regarding patients' fallings
      and medicines in top-down analysis is created clearly. Finally, we present new
      perspectives on ways of improving patient safety.

PMID- 22874189
TI  - Inventory of tools for Dutch clinical language processing.
AB  - Automated encoding of free-text clinical narratives using concepts from
      terminological systems is widely performed. However, the majority of natural
      language processing (NLP) tools and terminological systems involve the English
      language. As parts of the NLP process are language independent, and tools for
      various languages are available, an overview is needed to determine the
      applicability to performing NLP of Dutch medical texts. To this end an inventory
      of tools is created. A literature study and internet search were performed to
      describe available components for a Dutch NLP system, enabling to encode Dutch
      text as structured SNOMED CT output without the need to translate SNOMED CT in
      Dutch. We have found 31 papers, describing a variety of NLP frameworks and tools
      for the various NLP components for processing English and Dutch free text. Most
      of them are suitable for English free text, some of them are (also) usable for
      Dutch. To enable automated encoding of Dutch free text narratives, further
      research is needed to create a spelling checker, a negation detector, a domain
      specific abbreviation/acronym list, and a concept mapper (to map Dutch terms to
      concepts in a terminological system). Furthermore evaluation of performance for
      the Dutch 'medical' language is needed.

PMID- 22874191
TI  - Measuring lexical similarity methods for textual mapping in nursing diagnoses in
      Spanish and SNOMED-CT.
AB  - One of the current problems in the health domain is the reuse and sharing the
      clinical information between different professionals, as they are written in
      natural language using specific terminologies. To overcome this issue it is
      necessary to use a common terminology, like SNOMED-CT, allowing an information
      reuse that offers the health professionals the quickest access to quality
      information. In order to use this terminology all the other terminologies have to
      be mapped to it. One solution to perform that mapping is using a lexical
      similarity approach. In this paper we analyze the appropriateness of 15 lexical
      similarity methods for mapping a set of NANDA-I labels to a set of SMOED-CT
      descriptions in Spanish. Our aim is to establish how to choose the best algorithm
      in this domain, from the recall and the precision point of view. After running
      six different tests, we have established that the three best algorithms where
      those that maximize the recall, because they always return the best solution.

PMID- 22874192
TI  - A "meta"-perspective on "bit rot" of biomedical research data.
AB  - Research data management (RDM) is an important topic for biomedical research due
      to the issue of "bit rot". RDM aims to implement access to reliable digital data
      for local and distributed research groups. A key aspect for the understanding of
      data is the use of metadata. This understanding has been investigated on the
      basis of two use cases of the DFG project LABIMI/F: RDM for genome data and
      biomedical image data. The results show that metadata can improve research not
      only for others but also for the researcher himself. However, RDM is still far
      from integrating all biomedical data. In addition, RDM is not (yet) a valid
      approach for clinical trial data management.

PMID- 22874193
TI  - A semantic approach for digital long-term preservation of electronic health
      documents.
AB  - Long-term preservation of electronic patient health information is a key issue
      for life-long electronic health records, however, it is poorly implemented in
      healthcare institutions and little attention is given to problems like
      obsolescence of formats and EHR applications or changing regulations, which
      jeopardize reusability of information after decades of preservation. We present
      in this paper an ontology driven approach to digital preservation and related
      metadata management which seems to be superior to conventional concepts of the
      digital library world.

PMID- 22874194
TI  - Automated realtime data import for the i2b2 clinical data warehouse: introducing
      the HL7 ETL cell.
AB  - Clinical data warehouses are used to consolidate all available clinical data from
      one or multiple organizations. They represent an important source for clinical
      research, quality management and controlling. Since its introduction, the data
      warehouse i2b2 gathered a large user base in the research community. Yet, little
      work has been done on the process of importing clinical data into data warehouses
      using existing standards. In this article, we present a novel approach of
      utilizing the clinical integration server as data source, commonly available in
      most hospitals. As information is transmitted through the integration server, the
      standardized HL7 message is immediately parsed and inserted into the data
      warehouse. Evaluation of import speeds suggest feasibility of the provided
      solution for real-time processing of HL7 messages. By using the presented
      approach of standardized data import, i2b2 can be used as a plug and play data
      warehouse, without the hurdle of customized import for every clinical information
      system or electronic medical record. The provided solution is available for
      download at http://sourceforge.net/projects/histream/.

PMID- 22874195
TI  - Coupling K-nearest neighbors with logistic regression in case-based reasoning.
AB  - Case-based reasoning (CBR) systems use similarity functions to solve new problems
      with past situations. K-nearest neighbors algorithm (K-NN) have been used in CBR
      systems to define new cases status according to characteristics of past nearest
      cases. We proposed a new hybrid approach combining logistic regression (LR) with
      K-NN to optimize CBR classification. First, we analyzed the knowledge database by
      LR procedures and the Pearson residuals of the LR model were used to define
      cases' utility of the knowledge database into K-NN. Secondly, we compared the
      classification performances of LR model and K-NNs coupled or not with LR. Our
      results showed that the information provided by the residuals could be used to
      optimize the settings of K-NN and to improve CBR classification.

PMID- 22874196
TI  - Flexible solution for interoperable cloud healthcare systems.
AB  - It is extremely important for the healthcare domain to have a standardized
      communication because will improve the quality of information and in the end the
      resulting benefits will improve the quality of patients' life. The standards
      proposed to be used are: HL7 CDA and CCD. For a better access to the medical data
      a solution based on cloud computing (CC) is investigated. CC is a technology that
      supports flexibility, seamless care, and reduced costs of the medical act. To
      ensure interoperability between healthcare information systems a solution
      creating a Web Custom Control is presented. The control shows the database tables
      and fields used to configure the two standards. This control will facilitate the
      work of the medical staff and hospital administrators, because they can configure
      the local system easily and prepare it for communication with other systems. The
      resulted information will have a higher quality and will provide knowledge that
      will support better patient management and diagnosis.

PMID- 22874197
TI  - TEDIS, Pervasive Developmental Disorder' patients information system, preliminary
      results.
AB  - TEDIS, an information system dedicated to patients with Pervasive Developmental
      Disorder (PDD) was tested. Results focused on the process of behavioural changes
      among physicians and health professionals with regard to structured organized
      patient information.The experiment encouraged changes in professionals' habits
      for further documenting and systematizing patient information collection. TEDIS'
      project federated professionals for developing methods for a systematic and
      exhaustive patient data management, in a longitudinal and cross-domain
      perspective, for improving knowledge and health care management.

PMID- 22874198
TI  - Characteristics of patients at risk for adverse drug events: designing for
      patient safety and decision support.
AB  - Adverse drug events are a significant global health issue. In this paper we
      describe our research work to date in identifying the characteristics of patients
      who are at risk for adverse drug events. We conducted a focus group study with
      health professionals to identify those characteristics of patients that health
      professionals attend to if they believe a patient is at risk for an adverse drug
      event. This work is being undertaken in order to develop an electronic decision
      support system that will alert health professionals to the presence of such
      patient characteristics in order to support their clinical decision making.

PMID- 22874199
TI  - Clinical diagnosis support system based on case based fuzzy cognitive maps and
      semantic web.
AB  - Incorrect or improper diagnostic tests uses have important implications for
      health outcomes and costs. Clinical Decision Support Systems purports to optimize
      the use of diagnostic tests in clinical practice. The computerized medical
      reasoning should not only focus on existing medical knowledge but also on
      physician's previous experiences and new knowledge. Such medical knowledge is
      vague and defines uncertain relationships between facts and diagnosis, in this
      paper, Case Based Fuzzy Cognitive Maps (CBFCM) are proposed as an evolution of
      Fuzzy Cognitive Maps. They allow more complete representation of knowledge since
      case-based fuzzy rules are introduced to improve diagnosis decision. We have
      developed a framework for interacting with patient's data and formalizing
      knowledge from Guidelines in the domain of Urinary Tract Infection. The conducted
      study allowed us to test cognitive approaches for implementing Guidelines with
      Semantic Web tools. The advantage of this approach is to enable the sharing and
      reuse of knowledge from Guidelines, physicians experiences and simplify
      maintenance.

PMID- 22874200
TI  - Comparing Drools and ontology reasoning approaches for telecardiology decision
      support.
AB  - Implantable cardioverter defibrillators can generate numerous alerts.
      Automatically classifying these alerts according to their severity hinges on the
      CHA2DS2VASc score. It requires some reasoning capabilities for interpreting the
      patient's data. We compared two approaches for implementing the reasoning module.
      One is based on the Drools engine, and the other is based on semantic web
      formalisms. Both were valid approaches with correct performances. For a broader
      domain, their limitations are the number and complexity of Drools rules and the
      performances of ontology-based reasoning, which suggests using the ontology for
      automatically generating a part of the Drools rules.

PMID- 22874201
TI  - Decision support in trauma management: predicting potential cases of Ventilator
      Associated Pneumonia.
AB  - Ventilator Associated Pneumonia (VAP) is a complication of intubated trauma
      patients and a leading cause in Intensive Care Unit (ICU) mortality. Since early
      diagnosis, by specimen culture takes days to complete, an overuse of broad
      spectrum antibiotics is the usual treatment. As a result there is the risk of
      developing antibiotic resistant strains. Using an Artificial Neural Network (ANN)
      derived model to predict those at risk would result in reduced risk of resistant
      strains, a lowering of mortality rates and considerable savings in treatment
      costs. Artificial Neural Networks work well on classification problems, using
      feed-forward/back propagation methodology. Using the National Trauma Data Bank
      (V6.2) data files, Tiberius Software created the ANN models. Best models were
      identified by their Gini co-efficient, ability to predict the complication
      outcome selected, and their RMSE scores. The model ensemble for the complications
      recorded in the registry were determined, variables ranked and model accuracy
      recorded. Results show an effective model, able to predict to 85% of those likely
      to contract VAP and similar figures for those unlikely to contract VAP. This
      equates to 1 in 10 patients being missed, and 1 in 10 falsely being flagged for
      treatment. Important variables in model development are not related to
      physiological factors, but injury status and the treatment received (intubation
      and expected ICU stay more than 2 days). Application of a predictive model could
      reduce the number of false positives being treated in an ICU and identify those
      most at risk, thereby lowering treatment costs and potentially helping improve
      mortality rates.

PMID- 22874202
TI  - Knowledge-based tacrolimus therapy for kidney transplant patients.
AB  - Immunosuppressive therapy is necessary when patients with chronic kidney disease
      receive a kidney transplant. Certain immunosuppressive agents need therapeutic
      drug monitoring. The goal of this paper was to identify adaptation rules for
      Tacrolimus therapy from a clinical data set. For knowledge acquisition, patient
      data from 1995 to 2008 from the Department of Nephrology and Dialysis of the
      Vienna General Hospital were used, including patient demographics, laboratory
      parameters, time since kidney transplantation and other immuno-suppressive drugs
      administered. Tacrolimus was chosen from the available immunosuppressive drugs.
      By applying a regression tree, we create homogeneous groups of data. Models were
      generated for these groups that can predict the level of the drug concentration
      for the next ward round. A knowledge base was developed on the basis of the
      determined models, which is used within a clinical decision support system for
      Tacrolimus therapy planning, which was integrated into clinical routine.

PMID- 22874203
TI  - Proposal of diagnostic process model for computer based diagnosis.
AB  - We aim at making a diagnosis support system that can be put to practical use. We
      proposed a diagnostic process model based on simple knowledge which can be
      gleaned from textbooks. We defined clinical finding (CF) as a general concept for
      patient's symptom or findings etc., whose value is expressed by Boolean. We call
      the combination of several CFs a "CF pattern", and a set of CF patterns with
      concomitant diseases "case base". We consider diagnosis as a process of searching
      an instance from the case base whose CF pattern is concomitant with that of a
      patient. The diseases which have the same CF pattern are candidates for
      diagnosis. Then we select a CF which is present in part of the candidates and
      check whether it is present or absent in the patient in order to narrow down the
      candidates. Because the case base does not exist in reality, the probability of
      CF pattern is calculated by the product of CF occurrence rate assuming that
      occurrence of CF is independent. Therefore the knowledge required for diagnosis
      is frequency of disease under sex and age group and CF-disease relation (CF and
      its occurrence rate in the disease). By processing these two types of knowledge,
      diagnosis can be made.

PMID- 22874205
TI  - Challenges in evaluating telehealth through RCT-the problem of randomization.
AB  - Telehealth is heralded as a panacea to control burgeoning demand on healthcare
      resources and lack of streamlining in care delivery. However, evaluating the
      effectiveness of telehealth on health and care delivery outcomes through
      randomized controlled trials (RCTs) has been an issue of contention. This
      research investigates the issues that affect telehealth evaluation. The strategy
      adopted in this research involved conducting a qualitative longitudinal case
      study, in the UK. Data was collected through focus group discussions and
      interviews; and analyzed thematically. The results of this research indicate that
      there are both practical and methodological issues that affect evaluation of
      telehealth through RCT in healthcare. Addressing these issues is vital in order
      to understand how an evaluation strategy should be deployed, and whether it is
      suited to the healthcare context.

PMID- 22874206
TI  - eHealth indicators: results of an expert workshop.
AB  - eHealth indicators are needed to measure defined aspects of national eHealth
      implementations. However, until now, eHealth indicators are ambiguous or unclear.
      Therefore, an expert workshop "Towards an International Minimum Dataset for
      Monitoring National Health Information System Implementations" was organized. The
      objective was to develop ideas for a minimum eHealth indicator set. The proposed
      ideas for indicators were classified based on EUnetHTA and De-Lone & McClean, and
      classification was compared with health IT evaluation criteria classification by
      Ammenwerth & Keizer. Analysis of the workshop results emphasized the need for a
      common methodological framework for defining and classifying eHealth indicators.
      It also showed the importance of setting the indicators into context. The results
      will benefit policy makers, developers and researchers in pursuit of provision
      and use of evidence in management of eHealth systems.

PMID- 22874207
TI  - eHealth interoperability evaluation using a maturity model.
AB  - To further improve individual health and well-being, access to high quality and
      safe services, eHealth interoperability is a fundamental prerequisite. A mature
      interoperability between health systems will support health services organization
      and delivery, and improve citizens' awareness of how to prevent disease and
      preserve good health. Within this context, health institutions have to solve
      interoperability problems or prevent them to appear, and if possible avoid them
      before they occur by adapting good practices toward interoperability. This paper
      proposes an evaluation of the potential health interoperability using the MMEI
      methodology (Maturity Model for Enterprise Interoperability). It discusses how
      the MMEI model can be used to help institutions to avoid interoperability
      problems. A use case for a particular hospital is more closely examined.

PMID- 22874208
TI  - Exploring a methodology for eHealth indicator development.
AB  - Indicators provide a practical method to monitor and benchmark eHealth progress
      towards objectives set in local, national and international policies, and to
      offer evidence for eHealth management. There is no agreed methodology to develop
      and define these indicators. The purpose of this paper is to present a proposal
      for an indicator development methodology and indicator classification. This
      proposal combines expert-led top-down and community-based bottom-up approaches.
      It offers a holistic approach for developing indicators for measuring progress
      and impacts of eHealth development consisting of four phases: (1) defining the
      context for measurement, (2) defining the goal of measurement, (3) defining the
      methods for indicator selection and indicator categorization and (4) defining the
      data to be collected and analyzed to calculate the indicator. Our preliminary
      results will be used as a starting point for developing a more detailed
      description of methods for indicator development and for identifying and
      classifying eHealth indicators and on testing them in practice.

PMID- 22874209
TI  - Population-based clinical decision support: a clinical and economic evaluation.
AB  - Governments are investing in health information technologies (HIT) to improve
      care quality and reduce medical costs. However, evidence of these benefits is
      limited. We conducted a randomized trial of three clinical decision support (CDS)
      interventions in 20,180 patients: email to care managers (n=3329), reports to
      primary care administrators (n=3368), letters to patients (n=3401), and controls
      (10,082). At 7-month follow-up, the letters to patients group had greater use of
      outpatient services and higher outpatient and total medical costs; whereas, the
      other groups had no change in clinical events or medical costs. As our CDS
      interventions were associated with no change or an increase in medical costs, it
      appears that investments in HIT without consideration for organizational context
      may not be sufficient to achieve improvements in clinical and economic outcomes.

PMID- 22874210
TI  - Quality assurance and effectiveness of the medication process through tablet
      computers?
AB  - Medication errors during admission to hospitals pose a significant problem. Most
      of the severe medication errors may be related to dispensation and
      administration. The medication errors may be induced by cost savings and staff
      reduction characterizing the current health care system. The objective of this
      study is to evaluate whether implementation of tablet computers has potential to
      enhance the quality assurance and efficiency of the medication dispensing and
      administration stages. The study is based on a combination of participant
      observation, structured workshop and qualitative interviews. Data has primary
      been collected on a Danish hospital ward. The study concludes that the technology
      still needs to mature before implementation and that there is a constant need for
      redesign of the technology. However, the results also show that technology has
      the potential to improve patient safety in the dispensing and administration
      stages because of an easier control and overview of the medicine paradigm; right
      patient, right drug, right dose and right time. Additionally, the technology
      appears to have the potential to streamline work flow in the administration stage
      due to an improved barcode registration mechanism. However, the potential of a
      successful implementation depends on prior working routines in the individual
      hospital ward.

PMID- 22874211
TI  - A framework for user involvement and context in the design and development of
      safe e-Health systems.
AB  - Current approaches to health IT research and development emphasize the valuable
      role of users. However, differences amongst users, in how they are defined,
      involved and interact with health IT under conditions of varying complexity has
      received limited attention. Failure to acknowledge these differences makes
      assessments of the quality, reliability and transferability of results
      problematic. More importantly, as e-health systems are increasingly opened up to
      use by health consumers the implications of differences in the context of system
      use for patient safety require closer investigation. To support the safety of e
      Health systems, it is essential that where users are involved we can more
      accurately differentiate between types of users and their contexts of use and how
      these factors interact with usability and the risk of unintended consequences
      from such systems. This paper presents an extended three dimensional user-task
      context matrix for considering who users of healthcare applications are, their
      needs and their requirements under differing contexts of use.

PMID- 22874212
TI  - Analysis of metrics for the usability evaluation of EHR management systems.
AB  - Electronic health records are replacing conventional paper-based health records.
      For a doctor it is a working instrument, which can significantly reduce the time
      spent on paper work. Patients can benefit from accessing the electronic health
      records even though they usually do not have a medical background. Therefore,
      when specifying a graphical user interface (GUI) it is necessary to take into
      account the requirements of the different users: e.g. the functionality for the
      doctors and the presentation of data in an understandable manner for the
      patients. The study aims to review and analyze metrics used to evaluate the
      usability of user interfaces in health information systems. The scope of the
      search included the analysis of existing usability evaluating metrics that are
      applied both in healthcare and other domains, where the standard of storage and
      presentation of information are applied. We identified a set of metrics and
      evaluation methods that provide holistic evaluation facilities for graphical user
      interfaces.

PMID- 22874213
TI  - Low-Cost Rapid Usability Testing for health information systems: is it worth the
      effort?
AB  - Usability testing is a step of the usability engineering process that focuses on
      analyzing and improving user interactions with computer systems. This study was
      designed to determine if an approach known as Low-Cost Rapid Usability Testing
      can be introduced as a standard part of the system development lifecycle (SDLC)
      for health information syste ms in a cost effective manner by completing a full
      cost-benefit analysis of this testing technique. It was found that by introducing
      this technique into the system development lifecycle to allow for earlier
      detection of errors in a health information syste m it is possible for a health
      organization to achieve an estimated 36.5% to 78.5% cost savings compared to the
      impact of errors going undetected and potentially causing a technology-induced
      error. Overall it was found that Low-Cost Rapid Usability Testing can be
      implemented in a cost effective manner to develop health information systems, and
      computer systems in general, which will have a lower incidence of technology
      induced errors.

PMID- 22874214
TI  - Patient safety-oriented usability testing: a pilot study.
AB  - This paper focuses on the prevention of technology induced errors in Health
      Information Technology (HIT) applications through usability tests in which
      patient safety-oriented usability goals have been included. A case study presents
      the evaluation of a web-based medication-related Clinical Decision Support System
      (CDSS). Systematically defining beforehand usability goals according to the
      potential use errors is an objective and replicable approach to identify the
      strengths and weaknesses of an application in terms of patient safety.

PMID- 22874215
TI  - The role of simulation in clinical information systems development.
AB  - This paper describes the role of simulation involving end-users in Health
      Informatics. Simulation has long been established as a widely accepted method in
      clinical skills training. During the last decade simulation has also gained a
      place in the development and evaluation of clinical information systems.
      Simulation is especially well suited for the evaluation of human factors and
      organizational aspects in relation to application of information systems. In full
      scale simulation tests it is possible to evaluate socio-technical interaction. A
      near to real life experience can be achieved by creating high fidelity
      environments. The paper discusses how simulation may be used during the lifecycle
      of clinical information systems, and the requirements on simulation fidelity in
      various situations. We recommend that simulation should get a more prominent role
      in the design and evaluation of clinical information systems.

PMID- 22874216
TI  - Using video observation to gain insight into complex clinical work practices.
AB  - Experience shows that the precondition for development of successful health
      information-technologies (HIT) is a thorough insight into clinical work
      practices. In contemporary clinical work practices, clinical work and health
      information technology are closely integrated. Research within Virtual Centre for
      Health Informatics at Aalborg University, Denmark have during recent years
      focused on video observation to supplementing traditional ethnographical research
      methods in providing insight into complex clinical work practices. The objective
      of this paper is to argue for the potentials of the video observation method to
      inform and to improve HIT development compared to traditional ethnographic
      methods. Based on several studies conducted within the healthcare sector, we
      find, that the video observation method is superior to other ethnographical
      research methods when it comes to rapidly disclosing the complexity in clinical
      sociomaterial work practices. We also find that the video techniques used in the
      healthcare context allows us to revisit the field of observation through the
      data, to broaden our initial focus and to share data with both the clinical staff
      involved and other researchers. Hence, it provides us a more in depth insight in
      the complex clinical sociomaterial work practices than when observing by the use
      of pen and paper.

PMID- 22874217
TI  - ICU nurses' evaluations of integrated information displays on user satisfaction
      and perceived mental workload.
AB  - Consolidated information from multiple sources (patient monitors, electronic
      medical records, infusion pumps, ventilators, medication references) may improve
      nurses' work and patient safety. Objective. Two hypotheses were tested, that
      integrated information displays (a) improve nurses' satisfaction and (b) lower
      perceived mental workload. Methods. In a counter-balanced, repeated measures
      design (integrated vs. traditional display) 12 ICU nurses performed realistic
      tasks using both display types. Results. Nurses' user interaction satisfaction
      was higher with the integrated display and it received more positive comments.
      Nurses' mean perceived mental workload scores were also lower, having significant
      differences in effort and frustration dimensions. A lower mental workload may
      reduce errors and improve treatment times. Integrated information displays have
      great promise, but technological factors such as bidirectional device
      communication must be addressed if these displays are to achieve their potential
      for improving patient safety.

PMID- 22874218
TI  - Proactive authenticated notifications for health practitioners: two way human
      computer interaction through phone.
AB  - Notifications and alerts play an important role in clinical daily routine. Rising
      prevalence of clinical decision support systems and electronic health records
      also result in increasing demands on notification systems. Failure adequately to
      communicate a critical value is a potential cause of adverse events. Critical
      laboratory values and changing vital data depend on timely notifications of
      medical staff. Vital monitors and medical devices rely on acoustic signals for
      alerting which are prone to "alert fatigue" and require medical staff to be
      present within audible range. Personal computers are unsuitable to display time
      critical notification messages, since the targeted medical staff are not always
      operating or watching the computer. On the other hand, mobile phones and smart
      devices enjoy increasing popularity. Previous notification systems sending text
      messages to mobile phones depend on asynchronous confirmations. By utilizing an
      automated telephony server, we provide a method to deliver notifications quickly
      and independently of the recipients' whereabouts while allowing immediate
      feedback and confirmations. Evaluation results suggest the feasibility of the
      proposed notification system for real-time notifications.

PMID- 22874219
TI  - Small cause - big effect: improvement in interface design results in improved
      data quality - a multicenter crossover study.
AB  - In Germany the core data set for anesthesia version 3.0 was recently introduced
      for external quality assurance, which includes five surgical tracer procedures.
      We found a low rate of correctly documented tracers when compared to procedure
      data (OPS-Codes) documented separately. Examination revealed that the graphical
      user interface (GUI) contravened the dialogue principles as defined in EN ISO
      9241-110. We worked with the manufacturer to implement small improvements and
      roll out the software. A crossover study was conducted at a university hospital
      and a municipal hospital chain with five hospitals. All study sites and surgical
      tracer procedures combined, we found an improvement from 42% to 65% (p<0.001;
      N=34,610) correctly documented anesthesias. We also saw improvements for most of
      the observed surgical tracer procedures at all hospitals. Our results show the
      big effect small changes to the GUI can have on data quality. They also raise the
      question, if highly flexible and parameterized clinical documentation systems are
      suited to achieve high usability. Finding the right balance between GUIs designed
      by usability experts and the flexibility of parameterization by administrators
      will be a difficult task for the future and subject to further research.

PMID- 22874220
TI  - The use and usability of EPR systems in oncology.
AB  - This paper reports preliminary findings of a study relating to the development
      and use of electronic patient record (EPR) systems in cancer services. The
      research literature demonstrates an increasing emphasis on reporting clinical
      outcomes and the need for effective EPR systems and high quality information,
      which should ultimately influence the quality of life of patients. The study is
      interpretative and forms part a wider research programme to define and validate
      CICERO, a reference model for 'Onco-EPR' systems. Preliminary conclusions from
      the primary study site, a leading UK cancer treatment centre, confirm the
      requirement for more effective Onco-EPR system design and implementation planning
      with emphasis on the socio-technical aspects of health informatics.

PMID- 22874221
TI  - Usability evaluation of a guideline implementation system for cardiac
      rehabilitation: think aloud study.
AB  - Guidelines on cardiac rehabilitation (CR) state that a patient-tailored,
      comprehensive CR programme should be constructed for each patient based on a
      structured needs assessment procedure. We performed a usability evaluation with
      seven end-users of the MediScore CARDSS 2.0 system which implements such a
      procedure based on the Dutch guidelines. The analysis showed that users deviated
      strongly from the predefined data entry order; could not complete all subtasks
      for a complete needs assessment procedure, and needed more navigation actions
      than minimally required. We conclude that the design model of systems which
      implement guidelines requiring data entry should adapt to users' mental model
      concerning data entry to guarantee complete data collection.

PMID- 22874223
TI  - A semantic wiki for editing and sharing decision guidelines in oncology.
AB  - The Internet has totally changed the way information is published and shared in
      medicine. With web 2.0 and semantic web technologies, web applications allow now
      collaborative information editing in a way that can be reused by machines. These
      new tools could be used to in local health networks to promote the editing and
      sharing of medical knowledge between practitioners. Oncolor, a French oncology
      network, has edited 144 decision guidelines. These local guidelines rely upon
      national French guidelines and are built and updated collaboratively by medical
      experts. To improve working conditions, the need of an online collaborative tool
      has been expressed. This paper presents ONCOLOGIK, a semantic wiki approach for
      local oncology guideline editing. Semantic wikis allow online collaborative work
      and manage semantic annotations which can be reused automatically to bring new
      services. Applied to oncology guidelines, semantic technologies improve the
      guideline management and provide additional services such as targeted queries to
      external bibliographical resources.

PMID- 22874224
TI  - An engine for compliance checking of clinical guidelines.
AB  - Although, clinical guidelines are regarded as best practices for clinicians,
      clinician activities are not always compliant with guideline recommendations.
      This paper aims to improve clinician compliance with guidelines. We have
      developed an engine to automatically report three non-compliance situations: 1)
      guideline recommendations exist, and the clinician performed some activities, but
      not according to the guidelines; 2) guideline recommendations exist, but the
      clinician did nothing; 3) guideline recommendations do not exist, but the
      clinician performed some activities. In particular, we highlight effective time
      for compliance checking, as well as membership, numeric relationships, concept
      subsumption and contextualization. We deployed our engine to a clinical setting
      involving the daily care routine of diabetes patients, and generated non
      compliance reports for pilot users.

PMID- 22874225
TI  - Application of the logical elements rule method for formalization of clinical
      rules: case study of ACOVE-NLI.
AB  - The Logical Elements Rule Method (LERM) is a step-wise method for formalizing if
      then clinical rules. We applied LERM to a set of 40 clinical rules used in
      pharmacological quality assessment initiatives to assess (1) the amenability of
      the rules to formalization for decision support application (2) comparing
      adherence to rules that can and cannot be formalized, and (3) the usefulness of
      LERM as a tool for this task. Five rules could not be formalized, all due to
      unclear decision criteria. The adherence to ambiguous, non-formalizable rules was
      significantly lower than for formalizable ones (<0.001). We modified LERM with
      three additions for this task: (a) adding the sub-step of restating the rules in
      a consistent natural-language grammar before decomposing them into normal form,
      (b) creating rules to use in lieu of a controlled vocabulary, and (c) adding the
      requirement that a time frame must be defined for all medications (before
      hospitalization, current medication, new medication, or discharge medication).
      Although the clinical rules in this sample are all stated as semi-structured if
      then recommendations and are used in quality assessment initiatives, many
      ambiguities and inconsistencies in the clinical rules were identified by using
      LERM.

PMID- 22874226
TI  - Clinical guideline representation in a CDS: a human information processing
      method.
AB  - The Dutch Childhood Oncology Group (DCOG) has developed evidence-based guidelines
      for screening childhood cancer survivors for possible late complications of
      treatment. These paper-based guidelines appeared to not suit clinicians'
      information retrieval strategies; it was thus decided to communicate the
      guidelines through a Computerized Decision Support (CDS) tool. To ensure high
      usability of this tool, an analysis of clinicians' cognitive strategies in
      retrieving information from the paper-based guidelines was used as requirements
      elicitation method. An information processing model was developed through an
      analysis of think aloud protocols and used as input for the design of the CDS
      user interface. Usability analysis of the user interface showed that the
      navigational structure of the CDS tool fitted well with the clinicians' mental
      strategies employed in deciding on survivors screening protocols. Clinicians were
      more efficient and more complete in deciding on patient-tailored screening
      procedures when supported by the CDS tool than by the paper-based guideline
      booklet. The think-aloud method provided detailed insight into users' clinical
      work patterns that supported the design of a highly usable CDS system.

PMID- 22874227
TI  - Computerized clinical guidelines: current status & principles for future
      research.
AB  - Although it is widely accepted that the adoption of computerized clinical
      guidelines would improve the quality of the provided health care, their influence
      in the daily practice is limited. In this paper we provide insights on the core
      topics related to computer interpretable clinical guidelines and we present
      shortly the main approaches in the area. Then we discuss the current limitations,
      and we present three simple principles that according to our view should be
      adopted to enhance the penetration of computerized clinical guidelines in the
      health care organizations. The overall goal of this paper is not only to give
      readers a quick overview of the works in the area, but also to provide necessary
      insights for the practical understanding of the issues involved and draw
      directions for future research and development activities.

PMID- 22874228
TI  - Ontology-based computerization of acute coronary syndrome clinical guideline for
      decision support in the emergency department.
AB  - Managing cardiac diseases in an emergency department is a challenge, as it
      demands rapid decision-making in a life-threatening situation. This paper
      presents a knowledge model for clinical guideline mediated Clinical Decision
      Support System for Acute Coronary Syndrome (ACS), targeting the ED care setting.
      We take a healthcare knowledge management approach to model clinical guideline
      using a clinical guideline ontology that is used to computerize the clinical
      guideline on the management of ACS, published by the American Heart Association,
      as a first step toward developing a clinical decision support system suitable for
      emergency departments at tertiary hospitals in Saudi Arabia.

PMID- 22874229
TI  - A semiotic view on paper and mobile care data quality.
AB  - Data quality of paper health records remain problematic and little is known about
      mobile health data quality. A semiotic data quality framework is used as an
      analytical lens to identify the quality of data in care health service provision
      in resource-restricted communities. A mobile application was developed using a co
      design approach. The results of the empirical study indicate data quality
      problems on the syntactic, semantic, pragmatic and social semiotic levels. The
      social aspect of data quality is an important contributor of quality associated
      problems. It is important to consider this human involvement in the capturing and
      using of data for the value of care data to be fully utilized. With better
      quality data a better care service can be provided and ultimately resulting in
      better quality life.

PMID- 22874230
TI  - Challenges and issues of geolocation in clinical environment.
AB  - Reaching a good indoor geolocation without deploying extensive and expensive
      infrastructure is a challenge, because satellite positioning system is not
      available indoors. Geolocation could be of major use in healthcare facilities; to
      help care providers, visitors and patients to navigate, to improve movements and
      flows efficiency or to implement location-awareness systems. A system able to
      provide the location of a person in a hospital requires precision, multi-floors
      and obstacles management and should also perform in basements and outdoors. Such
      system needs also to be insensitive to environmental variations occurring in a
      hospital. These changes may be various kinds of obstacles. These can be the
      displacement of metallic objects, metallic machines, strong magnetic fields or
      simply human displacement. A system conforming to the above requirements can also
      answer various security questions, operational workflow management but also
      assist movement of people.

PMID- 22874231
TI  - Empower the patients with a dialogue-based web application.
AB  - Based on a clinical intervention study this paper adds to the significance of
      users involvement in design processes and substantiate the potential of online,
      flexible health informatics tools as useful components to accommodate
      organizational changes that short stay treatment demands. A dialogue-based web
      application was designed and implemented to accommodate patients' information and
      communication needs in short stay hospital settings. To ensure the system meet
      the patients' needs, both patients and healthcare professionals were involved in
      the design process by applying various participatory methods. Contextualization
      of the new application was also central in all phases to ensure a focus not only
      on the technology itself, but also the way it is used and in which relations and
      contexts. In evaluation of the tool, the patients' descriptions as user
      substantiate that the use of Internet applications can expand the time for
      dialogue between the individual patient and healthcare professionals. The
      patients experience being partners in an on going dialogue, and thereby are
      empowered, e.g. in managing their care even at home, as these dialogues generate
      individualized information.

PMID- 22874232
TI  - From clinical requirement to personalized wellness decision support: a data
      driven framework for computer-supported guideline refinement.
AB  - Personalized wellness decision support has gained significant attention, owing to
      the shift to a patient-centric paradigm in healthcare domains, and the consequent
      availability of a wealth of patient-related data. Despite the success of data
      driven analytics in improving practice outcome, there is a gap towards their
      deployment in guideline-based practice. In this paper we report on findings
      related to computer-supported guideline refinement, which maps a patient's
      guideline requirements to personalized recommendations that suit the patient's
      current context. In particular, we present a novel data-driven personalization
      framework, casting the mapping task as a statistical decision problem in search
      of a solution to maximize expected utility. The proposed framework is well suited
      to produce personalized recommendations based on not only clinical factors but
      contextual factors that reflect individual differences in non-clinical settings.
      We then describe its implementation within the guideline-based clinical decision
      support system and discuss opportunities and challenges looking forward.

PMID- 22874233
TI  - Interoperability design of personal health information import service.
AB  - Availability of personal health information for individual use from professional
      patient records is an important success factor for personal health information
      management (PHIM) solutions such as personal health records. In this paper we
      focus on this crucial part of personal wellbeing information management splutions
      and report the interoperability design of personal information import service.
      Key requirements as well as design factors for interfaces between PHRs and EPRs
      are discussed. Open standards, low implementation threshold and the
      acknowledgement of local market and conventions are emphasized in the design.

PMID- 22874234
TI  - Using a patient-centered approach for health and social care integration.
AB  - The drive in using health and social care resources more effectively has resulted
      in undertaking various efforts towards better coordination in order to improve
      patient-centered and personalized care for the individuals. This requires
      horizontal integration in terms of processes among health and social care
      organizations existing information systems (ISs) and personal health records
      (PHRs) in order to enable integrated patient information sharing among all the
      health and social care staff and individuals involved. Service-oriented and
      business process management (BPM) technologies are considered most appropriate
      for achieving such integration especially when is required to change existing
      processes and to integrate diverse information systems. On these grounds, a
      patient-centered approach is proposed for redesigning health and social care
      processes and for integrating diverse ISs and PHRs with the objective to meet
      holistic care goals.

PMID- 22874235
TI  - Accuracy of clinical data entry when using a computerized decision support
      system: a case study with OncoDoc2.
AB  - Some studies suggest that the implementation of health information technology
      (HIT) introduces unpredicted and unintended consequences including e
      iatrogenesis. OncoDoc2 is a guideline-based clinical decision support system
      (CDSS) applied to the management of breast cancer. The system is used by
      answering closed-ended questions in order to document patient data while
      navigating through the knowledge base until the best patient-specific recommended
      treatments are obtained. OncoDoc2 has been used by three hospitals in real
      clinical settings and for genuine patients. We analysed 394 navigations, recorded
      on a 10-month period, which correspond to 6,025 data entries. The data entry
      error rate is 4.2%, spread over 52% of incorrect navigations (N-). However, the
      overall compliance rate of clinical decisions with guidelines significantly
      increased from 72.8% (without CDSS) to 87.3% (with CDSS). Although this increase
      is lowered because of N- navigations (compliance rates are respectively 95% and
      80% for N+ and N- navigations), the benefits of HIT outweighted its disadvantages
      in our study.

PMID- 22874236
TI  - Elicitating patient patterns of physician non-compliance with breast cancer
      guidelines using formal concept analysis.
AB  - Because they provide patient-specific guideline-based recommendations, clinical
      decision support systems (CDSSs) are expected to promote the implementation of
      clinical practice guidelines (CPGs). OncoDoc2 is a CDSS applied to the management
      of breast cancer. However, despite it was routinely used during weekly
      multidisciplinary staff meetings (MSMs) at the Tenon Hospital (Paris, France),
      the compliance rate of MSMs' decisions with CPGs did not reach 100%. Formal
      Concept Analysis (FCA) has been applied to elicit formal concepts related to non
      compliance. A statistical pre-treatment of attributes has been proposed to
      leverage FCA and discriminate between compliant and non-compliant decisions.
      Among the 1,889 decisions made over a 3 year-period, 199 decisions of recommended
      re-excisions have been considered for analysis. In this sample, non-compliance
      was explained by uncommon clinical profiles and specific patient-centred clinical
      criteria.

PMID- 22874237
TI  - Evidence based electronic system to ensure quality of care in trauma patients.
AB  - Electronic patient records are important for quality health services. Aim of this
      study is to support the trauma patient care with the development of an electronic
      system. A survey was conducted in the Emergency Department (ED) of a University
      hospital to study the effectiveness of an electronic monitoring system in a group
      of trauma patients, as well as the acceptance of this electronic system by the
      health professionals of the ED. A questionnaire collected information about the
      perceptions of 50 health professionals working in the ED on various aspects of
      patient care. The 86% (Nu=43) replied that there is lack of staff working in
      their department, 44% (N=22) is satisfied with the co-operation with other
      departments and 48% (N=24) believe that they spend precious time in
      administrative work during the care. For the purpose of a more efficient patient
      monitoring there was developed an electronic trauma patient monitoring system
      which was evaluated by the above mentioned professionals. The severity, length of
      care and the health outcomes of 200 trauma patients, were investigated. Half of
      the patients (N=100) have been monitored by the electronic system and the other
      100 were monitored without the use of the system. The time between the admission
      and completion of the planned care was significantly lower in the electronic
      monitoring patient group (100+/-92 minutes) compared to the control group (149+/
      29 minutes).

PMID- 22874238
TI  - OpenEHR-based representation of guideline compliance data through the example of
      stroke clinical practice guidelines.
AB  - In light of the lack of integration between electronic health records and
      decision support, this research explores how semantic electronic health record
      technology, particularly openEHR, can be used to represent clinical practice
      guidelines (CPGs). We used the tool Visual Understanding Environment (VUE) to
      build a graphical representation of the European ischaemic stroke clinical
      management guidelines. We used openEHR archetypes to conceptually support this
      process and also to represent clinical concepts in stroke treatment compliance
      criteria. Our results show that, as an intermediate step in authoring computer
      interpretable guidelines, an openEHR-based representation of CPGs and their
      compliance criteria supports the process of identifying the relevant knowledge
      and data elements in the care process to be modelled. It further eases the
      separation of the CPGs into data and logic components and is useful as a
      communication means for guideline verification by clinicians. Additionally, we
      retrieved existing and authored new openEHR archetypes for the acute stroke
      clinical management process. We conclude that openEHR-based guideline and
      compliance data representations may be a promising first step in building future
      decision support applications that are well connected to the electronic health
      record, can be useful in locating discrepancies between different sets of
      guidelines within the same care context and provide a helpful tool for driving
      the archetype authoring and review process.

PMID- 22874239
TI  - Towards collaborative chronic care using a clinical guideline-based decision
      support system.
AB  - Few clinical guideline-based decision support systems (DSS) have been
      successfully applied in chronic disease management. This paper investigates how
      clinical guideline-based DSS can help to put innovative chronic care models into
      practice and improve the quality of chronic care. A prototype of a guideline
      based collaborative chronic care system called GC3 was developed based on a
      framework integrating guidelines into care workflow where a business process
      engine and a GELLO-based decision engine are integrated together to execute
      guidelines. We deployed the system in one of the largest hospitals in China and
      its affiliated community centers in order to manage type 2 diabetic patients.
      Pilot use of GC3 demonstrates its benefits to regional chronic care including
      evidence-based decision support, shared care content, improved clinician
      adherence to guidelines and enhanced patient self-management. This study verifies
      the feasibility and effectiveness in implementing collaborative chronic care
      across health providers using clinical guideline-based DSS.

PMID- 22874240
TI  - A standardized middleware as the core of a telemonitoring European Project.
AB  - In order to develop smart and innovative solutions which are able to realize the
      concept of care continuum, the use of a number of different multiple devices,
      based on heterogeneous technologies, is necessary. In this complex context it is
      important to study and design systems whose architecture ensure the
      interoperability between devices and service. A standardized middleware which is
      able to guarantee this important requirement within the European Project CHIRON,
      is presented in this article.

PMID- 22874241
TI  - Dicoogle Mobile: a medical imaging platform for Android.
AB  - Mobile computing technologies are increasingly becoming a valuable asset in
      healthcare information systems. The adoption of these technologies helps to
      assist in improving quality of care, increasing productivity and facilitating
      clinical decision support. They provide practitioners with ubiquitous access to
      patient records, being actually an important component in telemedicine and tele
      work environments. We have developed Dicoogle Mobile, an Android application that
      provides remote access to distributed medical imaging data through a cloud relay
      service. Besides, this application has the capability to store and index local
      imaging data, so that they can also be searched and visualized. In this paper, we
      will describe Dicoogle Mobile concept as well the architecture of the whole
      system that makes it running.

PMID- 22874242
TI  - Does telecare reduce the number of treatment days?
AB  - This paper analyzes the effect of telecare in reducing the number of days
      required for the treatment of telecare users. Statistical analysis was conducted
      on panel data about 400 individuals from 2002 to 2006 in Nishi-aizu Town,
      Fukushima Prefecture, Japan. Three estimation models were used, namely the
      Instrument Variable, Instrument Variable Panel, and system GMM (Generalized
      Method of Moments) methods, both to demonstrate causality and to ensure the
      robustness of the results. We attempted to reduce sample selection bias in this
      framework by controlling variables with bias. A negative correlation between
      outpatient days and telecare use was observed with the former two methods, while
      the system GMM proved causality for the effect of telecare in reducing the number
      of outpatient days. Telecare use reduced outpatient days in telecare users by 2.0
      days per year. This result is consistent with those of other telecare
      implementations in the US and the UK.

PMID- 22874243
TI  - Establishing end-to-end security in a nationwide network for telecooperation.
AB  - Telecooperation is used to support care for trauma patients by facilitating a
      mutual exchange of treatment and image data in use-cases such as emergency
      consultation, second-opinion, transfer, rehabilitation and out-patient
      aftertreatment. To comply with data protection legislation a two-factor
      authentication using ownership and knowledge has been implemented to assure
      personalized access rights. End-to-end security is achieved by symmetric
      encryption in combination with external trusted services which provide the
      symmetric key solely at runtime. Telecooperation partners may be chosen at
      departmental level but only individuals of that department, as a result of
      checking the organizational assignments maintained by LDAP services, are granted
      access. Data protection officers of a federal state have accepted the data
      protection means. The telecooperation platform is in routine operation and
      designed to serve for up to 800 trauma centers in Germany, organized in more than
      50 trauma networks.

PMID- 22874245
TI  - A loosely coupled framework for terminology controlled distributed EHR search for
      patient cohort identification in clinical research.
AB  - Heterogeneous data models and coding schemes for electronic health records
      present challenges for automated search across distributed data sources. This
      paper describes a loosely coupled software framework based on the terminology
      controlled approach to enable the interoperation between the search interface and
      heterogeneous data sources. Software components interoperate via common
      terminology service and abstract criteria model so as to promote component reuse
      and incremental system evolution.

PMID- 22874246
TI  - Key-linked on-line databases for clinical research.
AB  - Separating patient identification data from clinical data and/or information
      about biomaterial samples is an effective data protection measure, especially in
      clinical research employing "on-line", i.e., web-based, data capture. In this
      paper, we show that this specialised technique can be generalised into a network
      architecture of interconnected on-line databases potentially serving a variety of
      purposes. The basic idea of this approach consists of maintaining logical links,
      i.e., common record keys, between corresponding data structures in pairs of
      databases while keeping the actual key values hidden from clients. For client
      systems, simultaneous access to corresponding records is mediated by temporary
      access tokens. At the relational level, these links are represented by arbitrary
      unique record keys common to both databases. This architecture allows for
      integration of related data in different databases without replicating or
      permanently sharing this data in one place. Each participating on-line database
      can determine the degree of integration by specifying linkage keys only for those
      data structures that may be logically connected to other data. Logical links can
      de designed for specific use cases. In addition, each database controls user
      access by enforcing its own authorisation scheme. Another advantage is that
      individual database owners retain considerable leeway in adapting to changing
      local requirements without compromising the integration into the network. Beyond
      protecting individual subject identification data, this architecture permits
      splitting a cooperatively used data pool to achieve many kinds of objectives.
      Application examples could be clinical registries needing subject contact
      information for follow-up, biomaterial banks with or without genetic information,
      and automatic or assisted integration of data from electronic medical records
      into research data.

PMID- 22874247
TI  - Standardised representation of healthcare information in secondary care research:
      a Central England case study.
AB  - Interoperability and reuse of healthcare information, for patient care and
      clinical research, rely on standardised approaches in its representation. The
      medical domain is rich with terminologies and dictionaries to support the
      representation of clinical data, but these are not necessarily interoperable.
      Secondary care research has long been conducted with study-specific requirements,
      and the valuable information collected was, however, difficult to reuse and share
      due to incomplete data collection and its non-standard representation. As a way
      to resolve some of these issues, we are designing and building sustainable
      database applications that clinicians and researchers alike can use as research
      registries, with the main aim to have research-quality healthcare information for
      future research studies and trials. This paper looks at a case study of how these
      applications are being developed in Central England through the use of controlled
      vocabularies. Specialty teams are keen to improve the interoperability, sharing
      and reuse of health information within and across specialties.

PMID- 22874248
TI  - The Electronic Healthcare Record for Clinical Research (EHR4CR) information model
      and terminology.
AB  - A major barrier to repurposing routinely collected data for clinical research is
      the heterogeneity of healthcare information systems. Electronic Healthcare Record
      for Clinical Research (EHR4CR) is a European platform designed to improve the
      efficiency of conducting clinical trials. In this paper, we propose an initial
      architecture of the EHR4CR Semantic Interoperability Framework. We used a model
      driven engineering approach to build a reference HL7-based multidimensional model
      bound to a set of reference clinical terminologies acting as a global as view
      model. We then conducted an evaluation of its expressiveness for patient
      eligibility. The EHR4CR information model consists in one fact table dedicated to
      clinical statement and 4 dimensions. The EHR4CR terminology integrates reference
      terminologies used in patient care (e.g LOINC, ICD-10, SNOMED CT, etc). We used
      the Object Constraint Language (OCL) to represent patterns of eligibility
      criteria as constraints on the EHR4CR model to be further transformed in SQL
      statements executed on different clinical data warehouses.

PMID- 22874249
TI  - A DICOM architecture for clinicians and researchers.
AB  - Over the last years there has been a strong trend of publishing health data in
      anonymized format in order to make it available for research. This is also true
      for medical imaging where the DICOM standard is the predominant data format and
      network protocol. This paper proposes an extension to any DICOM networking
      infrastructure that permits sharing of medical images in an anonymized way.
      Standard DICOM software is utilized on client and server side. While offering
      researchers access to all images in anonymous format, the architecture enables
      authorized clinicians to access the same images including their original patient
      information (name, institution, etc.). Identifying parts and anonymous parts of
      the image data are stored to geologically different databases. Together with
      sophisticated network protocols, patient privacy is fully preserved.

PMID- 22874250
TI  - Ophiucus: RDF-based visualization tool for health simulation models.
AB  - Simulation modeling of population health is becoming increasingly popular for
      epidemiology research and public health policy-making. However, the acceptability
      of population health simulation models is inhibited by their complexity and the
      lack of established standards to describe these models. To address this issue, we
      propose Ophiuchus - an RDF (Resource Description Framework:
      http://www.w3.org/RDF/)-based visualization tool for generating interactive 2D
      diagrams of population health simulation models, which describe these models in
      an explicit and formal manner. We present the results of a preliminary system
      assessment and discuss current limitations of the system.

PMID- 22874251
TI  - Validation and discovery of genotype-phenotype associations in chronic diseases
      using linked data.
AB  - This study investigates federated SPARQL queries over Linked Open Data (LOD) in
      the Semantic Web to validate existing, and potentially discover new genotype
      phenotype associations from public datasets. In particular, we report our
      preliminary findings for identifying such associations for commonly occurring
      chronic diseases using the Online Mendelian Inheritance in Man (OMIM) and
      Database for SNPs (dbSNP) within the LOD knowledgebase and compare them with Gene
      Wiki for coverage and completeness. Our results indicate that Semantic Web
      technologies can play an important role for in-silico identification of novel
      disease-gene-SNP associations, although additional verification is required
      before such information can be applied and used effectively.

PMID- 22874252
TI  - A web-based tool for patients cohorts and Clinical Trials management.
AB  - Clinical Trials (CTs) play an increasingly important role in modern medicine.
      Often these types of studies, especially in the final phases, require
      collaboration between several hospitals, laboratories and institutions in
      different places or countries. The solution proposed is a template which exploits
      the principles of Networked Clinical Research and the strengths of Clinical Data
      Management Systems (CDMSs) commonly used (Electronic Data Capture (EDC),
      Electronic Medical Record (EMR) and Electronic Health Record (EHR). Therefore,
      the basic structure is a highly normalized and standardized database which is
      managed by a web platform and, only by recording the required information and
      developing web pages starting from predefined templates, it is possible to carry
      out new projects. The result is a hybrid CDMS which preserves the flexibility and
      user autonomy of EDC systems; and contemporarily, permits the creation of
      patients cohorts, as in EMR and EHR systems, in which to realize simultaneously
      different multicentric CTs in several medical fields.

PMID- 22874253
TI  - Designing and implementing a biobanking IT framework for multiple research
      scenarios.
AB  - This paper presents a biobanking IT framework, comprising a set of integrated
      biobanking information technology components. It provides adaptable and scalable
      IT support for varying biobanking scenarios, workflows and projects, while
      avoiding redundancy in data and technology. Feasibility of this approach is
      illustrated by implementations for four different biobanking projects at Erlangen
      University Hospital and with cooperating partners in Munster and Lubeck.

PMID- 22874254
TI  - Interoperability in clinical research: from metadata registries to semantically
      annotated CDISC ODM.
AB  - Planning case report forms for data capture in clinical trials is a labor
      insensitive and not formalized process. These CRFs are often neither standardized
      nor using defined data elements. Metadata registries as the NCI caDSR provide the
      capability to create forms based on common data elements. However, an exchange of
      these forms into clinical trial management systems through a standardized format
      like CDISC ODM is currently not offered. Thus, our objectives were to develop a
      mapping model between NCI forms and ODM. We analyzed 3012 NCI forms and included
      common data elements regarding their frequency and uniqueness. In this paper, we
      have created a mapping model between both formats and identified limitations in
      the conversion process: Semantic codes requested from the caDSR registry did not
      allow a proper mapping to ODM items and information like the number of module
      repetitions got lost. Summarized, it can be stated that our mapping model is
      feasible. However, mapping of semantic concepts in ODM needs to be specified more
      precisely.

PMID- 22874255
TI  - Requirements for semantic biobanks.
AB  - World-wide availability of biobank samples is a great desideratum for biomedical
      researchers. We describe the use case of biobank information retrieval that
      requires the semantic descriptions of biobank samples and of clinical
      information. In addition we sketch the foundations of an ontology for biobanks,
      as a basis on which distributed biobank indexing and retrieval systems can be
      built. We advocate that a detailed and robust representation of this kind of
      information improves and allows complex queries that will certainly arise to
      explore the full potential of biobanks.

PMID- 22874256
TI  - A semantic model for multimodal data mining in healthcare information systems.
AB  - Electronic health records (EHRs) are representative examples of
      multimodal/multisource data collections; including measurements, images and free
      texts. The diversity of such information sources and the increasing amounts of
      medical data produced by healthcare institutes annually, pose significant
      challenges in data mining. In this paper we present a novel semantic model that
      describes knowledge extracted from the lowest-level of a data mining process,
      where information is represented by multiple features i.e. measurements or
      numerical descriptors extracted from measurements, images, texts or other medical
      data, forming multidimensional feature spaces. Knowledge collected by manual
      annotation or extracted by unsupervised data mining from one or more feature
      spaces is modeled through generalized qualitative spatial semantics. This model
      enables a unified representation of knowledge across multimodal data
      repositories. It contributes to bridging the semantic gap, by enabling direct
      links between low-level features and higher-level concepts e.g. describing body
      parts, anatomies and pathological findings. The proposed model has been developed
      in web ontology language based on description logics (OWL-DL) and can be applied
      to a variety of data mining tasks in medical informatics. It utility is
      demonstrated for automatic annotation of medical data.

PMID- 22874257
TI  - Assessing the clinical uses of fuzzy detection results in the automated detection
      of CVC-related infections: a preliminary report.
AB  - Central venous catheters (CVCs) play an essential role in the care of the
      critically ill, but their use comes at the risk of infection. By using fuzzy set
      theory and logic to model clinical linguistic CVC-related infection criteria,
      clinical detection systems can detect borderline infections where not all
      infection parameters have been (fully) met, also called fuzzy results. In this
      paper we analyzed the clinical use of these results. We used a fuzzy-logic-based
      computerized infection control system for the monitoring of healthcare-associated
      infections to uncover fuzzy results and periods, after which we classified them,
      and used these classifications together with knowledge of prior CVC-related
      infection episodes in temporal association rule mining. As a result, we uncovered
      several rules which can help with the early detection of re-occurring CVC-related
      infections.

PMID- 22874259
TI  - Automatic extracting of patient-related attributes: disease, age, gender and
      race.
AB  - In the Evidence-based Medicine (EBM), PICO format is designed to easily and
      correctly search for the best available evidence. As the main element of PICO,
      the Patient/Problem (P) represents the attributes of patient in the clinical
      question and studies. In order to better understand the clinical problems,
      patient attribute identification is crucial and indispensable. Due to the
      richness of the human nature language, many issues like various term
      representations, grammar structures and abbreviations present challenges for
      automatically extracting the patient-related attributes from the unstructured
      data. In this paper, we employed the nature language processing (NLP)
      technologies to deeply analyze the linguistic characteristics of the attributes.
      Based on the NLP analysis results, we built the rule sets for different
      attributes and applied the rule-based approach to extract the patient-related
      attributes.

PMID- 22874258
TI  - Assessing the feasibility of data mining techniques for early liver cancer
      detection.
AB  - The objective of this study is to assess the feasibility of a data mining
      association analysis technique, the FP Growth algorithm, for the detection of
      associations of liver cancer, geographic location and demographic of patients.
      For the research, we are planning to use data extracted from electronic health
      record systems of three healthcare organizations in different geographic
      locations (Canada, Taiwan and Mongolia). The data are arranged into
      'transactions' which contain a set of data items focused around cancer diseases,
      geographic locations and patient demographics. This analysis produces association
      rules that indicate what combinations of demographics, geographic locations and
      patient characteristics lead to liver cancer.

PMID- 22874260
TI  - Estimating rheumatoid arthritis activity with infrared image analysis.
AB  - This work describes the development of a new diagnostic tool to assess the
      severity of rheumatoid arthritis (RA) using infrared image collection and
      analysis. Early work showed that the temperature distribution of joints of hands
      and knees of patients with RA was statistically significantly different from that
      of normal subjects. Current work identified ankles as also significant for an
      assessment of RA. Moreover, the patients were classified in three levels of RA
      severity (High, Medium, and Low) using a C5.0 decision tree classifier with
      excellent results: Sensitivity (true positive cases) of 96 % and a specificity
      (true negative cases) of 92%. Future work will automate the image analysis and
      test clinically by comparing to MR as ground truth.

PMID- 22874261
TI  - Fine-grained clinical outcome extraction and polarity classification.
AB  - Clinical outcome information is helpful for clinicians to understand the effect
      of a given intervention. Generally speaking, the outcome generated by an
      intervention has several aspects, and each aspect has different polarity. In this
      work we adopt structure learning algorithm to extract fine-grained outcome
      information and then determine the polarity of each aspect by trained classifier.
      Word and POS features are integrated by structure learning algorithm. The
      performance is evaluated on our labeled dataset. Experimental results indicate
      that although POS information can improve the performance of fine-grained outcome
      extraction it should be leveraged carefully.

PMID- 22874262
TI  - Evicase: an evidence-based case structuring approach for personalized healthcare.
AB  - The personalized medicine era stresses a growing need to combine evidence-based
      medicine with case based reasoning in order to improve the care process. To
      address this need we suggest a framework to generate multi-tiered statistical
      structures we call Evicases. Evicase integrates established medical evidence
      together with patient cases from the bedside. It then uses machine learning
      algorithms to produce statistical results and aggregators, weighted predictions,
      and appropriate recommendations. Designed as a stand-alone structure, Evicase can
      be used for a range of decision support applications including guideline
      adherence monitoring and personalized prognostic predictions.

PMID- 22874263
TI  - Reusable data in public health data-bases-problems encountered in Danish
      Children's Database.
AB  - Denmark have unique health informatics databases e.g. "The Children's Database",
      which since 2009 holds data on all Danish children from birth until 17 years of
      age. In the current set-up a number of potential sources of errors exist - both
      technical and human-which means that the data is flawed. This gives rise to
      erroneous statistics and makes the data unsuitable for research purposes. In
      order to make the data usable, it is necessary to develop new methods for
      validating the data generation process at the municipal/regional/national level.
      In the present ongoing research project, two research areas are combined: Public
      Health Informatics and Computer Science, and both ethnographic as well as system
      engineering research methods are used. The project is expected to generate new
      generic methods and knowledge about electronic data collection and transmission
      in different social contexts and by different social groups and thus to be of
      international importance, since this is sparsely documented in the Public Health
      Informatics perspective. This paper presents the preliminary results, which
      indicate that health information technology used ought to be subject for
      redesign, where a thorough insight into the work practices should be point of
      departure.

PMID- 22874264
TI  - Secondary use of clinical data in healthcare providers - an overview on research,
      regulatory and ethical requirements.
AB  - Hospital providers, physicians and researchers are interested in a cross
      institutional use of their data for clinical research. This interest has led to
      the question whether the scientific potential of the data stored in so many
      different systems can be unfolded by the establishment of a cross-institutional
      medical data warehouse. The aim of this paper is to describe the ethical and
      regulatory requirements and to develop a solution architecture considering
      technical and organisational aspects. The present paper uses a structured
      approach to collect user requirements. The requirements are discussed with legal
      experts. The work was complemented by extended literature research. An essential
      requirement is the cross-institutional merging of the data. Here, aspects of data
      protection as the informed consent, or transparency must be considered. In
      addition it is essential to protect the researchers through transparency from
      accusations on publication bias. Technical and organisational solutions in
      combination of data protection, and data security enable an operation of a
      central medical data warehouse in compliance with the law. The usage of this
      infrastructure for research can contribute to an improvement of the treatment
      quality, and patient safety if there is an appropriate transparency. This
      contributes to innovation and added value of a hospital group.

PMID- 22874265
TI  - Standardizing intensive care device data to enable secondary usages.
AB  - To represent medical device observations in a format that is consumable by
      clinical software, standards like HL7v3 and ISO/IEEE 11073 should be used
      jointly. This is demonstrated in a project with Drager Medical GmbH focusing on
      their Patient Data Management System (PDMS) in intensive care, called Integrated
      Care Manager (ICM). Patient and device data of interest should be mapped to
      suitable formats to enable data exchange and decision support. Instead of mapping
      device data to target formats bilaterally we use a generic HL7v3 Refined Message
      Information Model (RMIM) with device specific parts adapted to ISO/IEEE 11073
      DIM. The generality of the underlying model (based on Yuksel et al. [1]) allows
      the flexible inclusion of IEEE 11073 conformant device models of interest on the
      one hand and the generation of needed artifacts for secondary usages on the other
      hand, e.g. HL7 V2 messages, HL7 CDA documents like the Personal Health Monitoring
      Report (PHMR) or web services. Hence, once the medical device data are obtained
      in the RMIM format, it can quite easily be transformed into HL7-based standard
      interfaces through XSL transformations because these interfaces all have their
      building blocks from the same RIM. From there data can be accessed uniformly,
      e.g. as needed by Drager's decision support system SmartCare [2] for automated
      control and optimization of weaning from mechanical ventilation.

PMID- 22874266
TI  - Why is clinical information not reused?
AB  - Reuse of clinical information plays a key role in the vision of a health sector
      with comprehensive semantic and pragmatic interoperability. Several papers have
      dealt with the secondary reuse of information, e.g. for statistics or research,
      while the primary reuse - clinical information reused in a clinical setting - has
      received less attention. On the basis of a qualitative literature review, this
      paper creates a categorised overview of the different causes to refrain from
      reuse of clinical information in clinical settings. The categorisation
      contributes to a greater understanding of failing reuse of clinical information
      in clinical settings, and it can probably be used in designing, evaluating and
      optimising clinical information systems. Further, it is speculated that the
      categorisation can be used in the process of identifying the concepts that
      constitute the context of clinical information.

PMID- 22874268
TI  - Archetype based search in an IHE XDS environment.
AB  - To prevent information overload of physicians when accessing EHRs we introduce a
      method to extend the IHE XDS profile metadata-based search towards a content
      based search. Detailed queries are created based on predefined information needs
      mapped to ISO/EN 13606 Archetypes. They are aggregated to a metadata-based query
      to retrieve all relevant documents, which are then analyzed for the desired
      contents. The results are presented in a tabular form. The content-based search
      in IHE-XDS could be implemented efficiently and was found helpful by the
      evaluating physicians.

PMID- 22874269
TI  - Concepts for a personal health record.
AB  - Healthcare is about information. It is usually assumed that personal health
      information exists primarily for professional's use but well informed patients
      motivate better informed professionals. A longitudinal health record containing a
      patient's medical history has been the holy grail of healthcare. Personal
      Electronic Health Records (P-EHR) hold the potential to transform healthcare by
      providing a complete set of patient managed information. We present a portable P
      EHR's functionalities from the patient's perspective.

PMID- 22874270
TI  - Enhancing the many-to-many relations across IHE document sharing communities.
AB  - The Integrating Healthcare Enterprise (IHE) initiative is an ongoing project
      aiming to enable true inter-site interoperability in the health IT field. IHE is
      a work in progress and many challenges need to be overcome before the healthcare
      Institutions may share patient clinical records transparently and effortless.
      Configuring, deploying and testing an IHE document sharing community requires a
      significant effort to plan and maintain the supporting IT infrastructure. With
      the new paradigm of cloud computing is now possible to launch software devices on
      demand and paying accordantly to the usage. This paper presents a framework
      designed with purpose of expediting the creation of IHE document sharing
      communities. It provides semi-ready templates of sharing communities that will be
      customized according the community needs. The framework is a meeting point of the
      healthcare institutions, creating a favourable environment that might converge in
      new inter-institutional professional relationships and eventually the creation of
      new Affinity Domains.

PMID- 22874271
TI  - Standardized EHR interoperability - preliminary results of a German pilot project
      using the archetype methodology.
AB  - The mobility of doctors and patients asks for multilingualism of electronic
      health record (EHR) systems: Doctors might face language problems using foreign
      medical information systems; people working abroad ask for continuous care which
      requires the treating physician to consult and understand the patient's health
      record. To address these linguistic and interoperability issues a solution is
      being developed that is based on widely acclaimed standards. Medical concepts
      that are derived from ASTM CCR define an interface model (based on ISO 13606). A
      server manages the data exchange between heterogeneous systems based on the
      interface model. It provides web services (automatic) and web forms (manual) and
      performs a transformation from the legacy scheme to the common structure.
      Furthermore, the server provides rich visualization capabilities (e.g. language
      switch, custom charts etc.) which are useful for those EHR systems that don't
      provide these features.

PMID- 22874272
TI  - The FBE development project: toward flexible electronic standards-based bio
      psycho-social individual records.
AB  - Under the ARCHITRAVE programme aimed at redesigning the regional health and
      social information system, the alpha version of a new web application was
      developed using the International Classification of Functioning, Disability and
      Health (ICF) and other medical terminology systems as a basis for a flexible
      electronic standards-based bio-psycho-social record. The web application was
      developed in order to collect information according to a multiaxial assessment
      framework consistent with the model of functioning adopted by the ICF. The web
      application translates information collected in natural language into ICF and
      releases outputs at different stages of the assessment process useful in
      evaluating clinical and social outcomes, distinguishing between functioning and
      disability in the same functioning profile and planning reasonable adaptations to
      overcome disability. The alpha version works in Italian and was adapted to the
      Italian welfare system/services/policies, but an international version working in
      other languages/welfare systems can be designed. The first field trial is ongoing
      in the Friuli Venezia Giulia Region, implementing the regional Health and Social
      Action Plan 2010-2012.

PMID- 22874273
TI  - An EMR based cancer diary - utilisation and initial usability evaluation of a new
      cancer data visualization tool.
AB  - We present an EMR based approach to visualize all cancer relevant data in a so
      called cancer diary at a single glance. System log and results of a user survey
      demonstrate increasing use and good usability of the cancer diary compared to
      traditional searches for relevant information in the entire patient EMR. We
      conclude that a cancer diary, aggregating data of diagnostic staging, tumor
      conference decisions and therapeutic actions may be a valuable EMR extension for
      hospitals focusing on cancer care e.g. within comprehensive cancer centers.

PMID- 22874274
TI  - Automatic detection of inconsistencies between free text and coded data in
      Sarcoma discharge letters.
AB  - Discordance between data stored in Electronic Health Records (EHR) may have a
      harmful effect on patient care. Automatic identification of such situations is an
      important yet challenging task, especially when the discordance involves
      information stored in free text fields. Here we present a method to automatically
      detect inconsistencies between data stored in free text and related coded fields.
      Using EHR data we train an ensemble of classifiers to predict the value of coded
      fields from the free text fields. Cases in which the classifiers predict with
      high confidence a code different from the clinicians' choice are marked as
      potential inconsistencies. Experimental results over discharge letters of sarcoma
      patients, verified by a domain expert, demonstrate the validity of our method.

PMID- 22874275
TI  - Fragmentation of diabetes treatment in Austria - an indicator for the need for
      shared electronic health record systems.
AB  - Shared electronic health record (EHR) systems aim to support continuity of care
      within the joint treatment of a patient by a community of cooperating care
      providers. By analyzing the fragmentation of care of Austrian diabetes patients,
      we aim to find evidence whether there is actually a need for shared EHR systems
      in this context. Our results show that almost three quarters of the observed
      diabetes patients visit two or more different care providers during their
      diabetes-related visits. Overall, our findings strongly support the demand for
      shared EHR systems for the treatment of diabetes patients.

PMID- 22874276
TI  - Health data collecting and sharing: case studies of Czech e-health applications.
AB  - The paper shows the importance of e-health applications for electronic healthcare
      development. It describes several e-health applications for health data
      collecting and sharing that are running in the Czech Republic. These are IZIP
      system, electronic health record MUDR and K4CARE project applications. The e3
      health concept is considered as a tool for judging e-health applications in
      different healthcare settings.

PMID- 22874277
TI  - Ontology-based reusable clinical document template production system.
AB  - Clinical documents embody professional clinical knowledge. This paper shows an
      effective clinical document template (CDT) production system that uses a clinical
      description entity (CDE) model, a CDE ontology, and a knowledge management system
      called STEP that manages ontology-based clinical description entities. The
      ontology represents CDEs and their inter-relations, and the STEP system stores
      and manages CDE ontology-based information regarding CDTs. The system also
      provides Web Services interfaces for search and reasoning over clinical entities.
      The system was populated with entities and relations extracted from 35 CDTs that
      were used in admission, discharge, and progress reports, as well as those used in
      nursing and operation functions. A clinical document template editor is shown
      that uses STEP.

PMID- 22874278
TI  - The distributed use of electronic emergency-department whiteboards.
AB  - At emergency departments (EDs), electronic whiteboards are introduced to provide
      a better overview and to support clinicians in spending more time with patients.
      Often, the main difference between electronic and dry-erase whiteboards is that
      electronic whiteboards provide distributed access to whiteboard information. We
      investigate the distributed use of whiteboards at one ED by analyzing seven
      months of log data. Distributed use is far most frequent among the secretaries,
      indicating that whiteboards serve multiple uses. The physicians and nurses make
      little distributed use of the whiteboard and when they do it is to prepare for
      seeing and to document having seen a patient, rather than in patient rooms with
      the patients. Important reasons for the limited distributed use among physicians
      and nurses appear to be a frequent need and practice of visiting the physical
      information hub of the ED. The information hub features a permanent wall-mounted
      display of the electronic whiteboard and this display, rather than distributed
      access, is preferred by physicians and nurses.

PMID- 22874279
TI  - A data-driven living review for pharmacogenomic decision support in cancer
      treatment.
AB  - With drastically decreasing costs of genetic sequencing, it has become feasible
      to use individual genetic markers to optimize treatment selection in cancer
      therapy. However, it is still difficult for medical practitioners to integrate
      these new kinds of data into clinical routine, since available information is
      growing rapidly. We demonstrate how a blend of manual curation and automated data
      extraction and evidence synthesis can be used to generate a 'living review', a
      summarization of current evidence on cancer classification, corresponding genetic
      markers, genetic tests and treatment options that can be used by clinicians to
      refine treatment choices. In contrast to a classical review, this automated
      'living review' offers the opportunity of automatically updating core content
      when available data changes, making it easier to keep an overview of the best
      current evidence. We discuss some of the findings we made while creating a
      prototype of a 'living review' for colorectal cancer pharmacotherapy.

PMID- 22874280
TI  - Electronic medication ordering with integrated drug database and clinical
      decision support system.
AB  - Medication errors have been identified as one of the most important causes of
      adverse drug events. Computerized physician order-entry (CPOE) systems, coupled
      with decision support (Medication allergy checking, drug interactions, and dose
      calculations), are considered to be appropriate solutions for reducing medication
      errors and standardizing care. It is quite useful if clinical information system
      (CIS) supports order sets, which help with standardizing care, preventing
      omission errors, and expediting the ordering process. Order sets are predefined
      groups of orders pertinent to one or more specific clinical conditions or
      diagnoses. The article describes how a clinical information system can be used to
      support medication process (prescribing, ordering, dispensing, administration and
      monitoring) and offer participating medical teams real time warnings and key
      information regarding medications and patient status, thus reducing medication
      errors. Integrated electronic prescribing support system benefits for total
      parenteral nutrition (TPN) are discussed at the end.

PMID- 22874281
TI  - Isolation of patients with vancomycin resistant enterococci (VRE): efficacy of an
      electronic alert system.
AB  - This study investigates the implementation of an alert system for the isolation
      of vancomycin resistant enterococci (VRE) colonized patients. Given the risk of
      admitting a patient colonized by VRE it is necessary to implement efficient
      isolation measures. An electronic alert system integrated into a health
      information system (HIS) could help with the detection of these patients and
      their isolation in proper units. OBJECTIVES: Determine the efficacy of an
      electronic alert system in improving the rate of properly isolation of patients
      colonized with VRE. METHODS: two consecutive series of admission in adults units
      of 67 patients that were infected or colonized with VRE were compared. The time
      period of the study was six months before the implementation of the alert system
      and six months post-implementation of the system. RESULTS: The proportion of
      admission with proper isolation of the patient in correct units increased 44%
      after the alert system implementation. CONCLUSION: The implementation of an alert
      system improved the proportion of properly isolated patients with VRE.

PMID- 22874282
TI  - Knowledge-analytics synergy in Clinical Decision Support.
AB  - Clinical Decision Support (CDS) systems hold tremendous potential for improving
      patient care. Most existing systems are knowledge-based tools that rely on
      relatively simple rules. More recent approaches rely on analytics techniques to
      automatically mine EHR data to reveal meaningful insights. Here, we propose the
      Knowledge-Analytics Synergy paradigm for CDS, in which we synergistically combine
      existing relevant knowledge with analytics applied to EHR data. We propose a
      framework for implementing such a paradigm and demonstrate its principles over
      real-world clinical and genomic data of hypertensive patients.

PMID- 22874284
TI  - Indicators of data quality: revision of a guideline for networked medical
      research.
AB  - Data quality significantly impacts the reliability and validity of empirical
      medical research. Specific measures can be used to check the quality of data
      during operation of a research project like a register. Furthermore these
      indicators allow an assessment of data quality independently from the institution
      responsible for data recording. A previously developed set of 24 data quality
      indicators was compared with measures of three research projects, each
      representing a specific view on the topic. The structure of the set was
      confirmed, being able to capture most of the projects' measures under the
      headings plausibility, organization, and correctness. Solely two indicators about
      metadata could not be appropriately mapped. However, several measures not
      considered so far were added to reach a number of 51 quality indicators in a
      first draft of a revised set. Most of the new indicators refine existing ones; e.
      g. the indicator "allowed values for missings" refines the existing indicator
      "allowed values for qualitative data elements". Seven projects' measures
      contribute supplementary aspects of data quality. The draft of the revised set of
      quality indicators will now be reviewed within and beyond the group.

PMID- 22874285
TI  - Relevance of drug-drug interaction in the ICU - perceptions of intensivists and
      pharmacists.
AB  - Relevancy of potential drug-drug interactions (pDDIs) is crucial in alerting
      system design. However, the way this relevancy is perceived is not well
      understood. The main objective of this study was to gauge and identify
      differences in perceptions of intensivists and pharmacists about pDDI relevancy
      in the ICU. Interactions were defined according to the national medication
      database using a computerized algorithm. Intensivists and pharmacists filled in a
      questionnaire to score their perceptions on relevancy of encountered pDDIs types.
      We conducted a focus group session to discuss pDDIs receiving markedly different
      relevancy scores. The questionnaire addressed 53 pDDI types. Pharmacists rated 29
      pDDI types (54.7%) in the broad category "relevant" versus 16 (30.2%) for
      intensivists (p-value<0.001). The pharmacists and intensivists gave the same
      scores for 23 pDDI types (12 as relevant, and 11 as not relevant), and scored 30
      types differently. The focus group discussion resulted in a total of 36 relevant
      and 17 not relevant types. Compared to the pharmacists in this panel, the
      intensivists were less inclined to consider a pDDI type as relevant. It is
      important to tailor medication databases with information about evidence and
      severity of pDDIs to the environment in which they are used.

PMID- 22874286
TI  - Organizing data quality assessment of shifting biomedical data.
AB  - Low biomedical Data Quality (DQ) leads into poor decisions which may affect the
      care process or the result of evidence-based studies. Most of the current
      approaches for DQ leave unattended the shifting behaviour of data underlying
      concepts and its relation to DQ. There is also no agreement on a common set of DQ
      dimensions and how they interact and relate to these shifts. In this paper we
      propose an organization of biomedical DQ assessment based on these concepts,
      identifying characteristics and requirements which will facilitate future
      research. As a result, we define the Data Quality Vector compiling a unified set
      of DQ dimensions (completeness, consistency, duplicity, correctness, timeliness,
      spatial stability, contextualization, predictive value and reliability), as the
      foundations to the further development of DQ assessment algorithms and platforms.

PMID- 22874287
TI  - Quality assessment of automatically extracted data from GPs' EPR.
AB  - There are many secondary benefits to collecting routine primary care data, but we
      first need to understand some of the properties of this data. In this paper we
      describe the method used to assess the PPV and sensitivity of data extracted from
      Belgian GPs' EPR (diagnoses, drug prescriptions, referrals, and certain
      parameters), using data collected through an electronic questionnaire as a gold
      standard. We describe the results of the ResoPrim phase 2 project, which involved
      4 software systems and 43 practices (10,307 patients). This method of assessment
      could also be applied to other research networks.

PMID- 22874288
TI  - Safety of a web-based insulin titration system for patients with type 2 diabetes
      mellitus - pilot study.
AB  - The treatment of type 2 diabetes patients with insulin requires active dose
      titration to obtain optimal glycemic control. We developed a web-based decision
      support system to guide patients in performing the titration task autonomously,
      at their homes. The system is based on a clinically validated algorithm. The aim
      of this study was to test the safety of the system in a pilot implementation in
      clinical practice. Patients were blinded from the advice given by the system and
      instead received insulin dosing advice given by caregivers. At the end of the
      pilot, advice of the system were evaluated on safety by an expert panel. In this
      pilot study six patients used the web-based system at their home. In total, 48
      advice were logged in the system resulting in eighteen deviating systems dosing
      advice as compared to the advice of the caregiver. Evaluation of the eighteen
      deviating systems advice lead to the detection of one unsafe advice indicating a
      need to extend the algorithm with an additional safety decision rule.

PMID- 22874289
TI  - The role of electronic checklists - case study on MRI-safety.
AB  - Checklists can be used to improve and standardize safety critical processes and
      their communication. The introduction of potentially harmful medical technology
      and equipment has created additional requirements for the safe delivery of health
      care. We have studied the implementation of an electronic checklist to ensure the
      safety of patients scheduled for Magnetic Resonance Imaging examinations. Through
      a combination of observations and semi-structured interviews we investigated how
      health care workers in a Norwegian University hospital dealt with variations in
      checklist compliance, missing and lack of information. The checklist provided
      different functionality for the different users, ranging from a memory/attention
      support to a standardized form of communication on safety matters. However, the
      rigidity afforded by the electronic implementation, showed some serious drawbacks
      over the prior, simpler, paper-based versions.

PMID- 22874290
TI  - EHR and data protection issues in Italy.
AB  - Technological progresses and the changed way to collect, access and use data are
      at the bottom of the European Commission proposal for a "General Data Protection
      Regulation" (25 January 2012). Implications of safeguarding privacy and
      harmonization of existing rules are extremely important also for national Health
      Systems. Mobility of patients and health professionals as well as cross-border
      healthcare connected with the increasing use of Information and Communication
      Technologies in Healthcare Services are modifying traditional medical approaches
      and applications. New tools, as Electronic Health Records, provide significant
      benefits as empowering health consumers and minimizing health costs. Anyway, EHRs
      have limits: for example, they should cause risks for individuals, professionals
      and institutions in terms of personal injuries and liabilities. In this scenario,
      it's evident that technical aspects (as health standards and interoperability)
      are as important as legal and regulatory privacy issues. Presently, mandatory
      acts on the protection of individuals with regard to the processing of health e
      Data still missing at all levels. Italy is adopting binding and non-binding legal
      documents to tackle the problem. Are they enough?

PMID- 22874291
TI  - Ontology based log content extraction engine for a posteriori security control.
AB  - In a posteriori access control, users are accountable for actions they performed
      and must provide evidence, when required by some legal authorities for instance,
      to prove that these actions were legitimate. Generally, log files contain the
      needed data to achieve this goal. This logged data can be recorded in several
      formats; we consider here IHE-ATNA (Integrating the healthcare enterprise-Audit
      Trail and Node Authentication) as log format. The difficulty lies in extracting
      useful information regardless of the log format. A posteriori access control
      frameworks often include a log filtering engine that provides this extraction
      function. In this paper we define and enforce this function by building an IHE
      ATNA based ontology model, which we query using SPARQL, and show how the a
      posteriori security controls are made effective and easier based on this
      function.

PMID- 22874292
TI  - Recognition and privacy preservation of paper-based health records.
AB  - While the digitization of medical data within electronic health records has been
      introduced in some areas, massive amounts of paper-based health records are still
      produced on a daily basis. This data has to be stored for decades due to legal
      reasons but is of no benefit for research organizations, as the unstructured
      medical data in paper-based health records cannot be efficiently used for
      clinical studies. This paper presents a system for the recognition and privacy
      preservation of personal data in paper-based health records with the aim to
      provide clinical studies with medical data gained from existing paper-based
      health records.

PMID- 22874293
TI  - Towards human-centric visual access control for clinical data management.
AB  - We propose a novel human-centric, visual, and context-aware access control (AC)
      system for distributed clinical data management and health information systems.
      Human-centricity in this context means that medical staff should be able to
      configure AC rules, both in a timesaving and reliable manner. Since medical data
      often includes (meta-) information about a patient, it is essential that an AC
      system includes the patient into the AC process. To cater for the strong security
      needs in the medical domain, both the AC policy creation by medical staff as well
      as the patient-interaction feature need to be taken into account. While
      traditional AC systems offer sufficient security in theory, they lack in comfort
      and flexibility and as a result find no widespread acceptance with non tech-savvy
      users. Distributed medical institutions could enormously benefit from the
      opportunity of dynamic AC configuration at an end-user level while adhering to
      legal, ethical or other privacy requirements. Hence, this paper presents a human
      centric visual AC model for medical data, addressing usability, information
      security and patient interaction.

PMID- 22874294
TI  - Watermarking as a traceability standard.
AB  - The exponential increase in the number of electronic document exchanges in
      healthcare has considerably increased the risk of document drop-out or address
      errors. It may therefore be important to know to whom the information belongs and
      who produced it. This becomes a major concern when the document has been involved
      in processes leading to the choice of therapy and eventually in cases where
      patients seek damages for medical malpractice. Watermarking, which is the
      embedding of security elements, such as a digital signature, within a document,
      can help to ensure that a digital document is reliable. However, at the same
      time, questions arise about the validity of watermarking-based evidence. In this
      paper, beyond the technical aspects, we discuss the worldwide legal acceptability
      of watermarking and the need for its recognition as a standard according to
      technical characteristics that the CEN and ISO need to agree on.

PMID- 22874295
TI  - A statistics-based approach of contextualization for adverse drug events
      detection and prevention.
AB  - Several papers propose to take contexts into account for adverse drug events
      (ADE) detection and prevention, notably to decrease over-alerting of clinical
      decision support systems (CDSS). However, no statistical argument has been
      published till now. This works demonstrates, based on statistical analysis, that
      contextualization is necessary for ADE detection and prevention by 3 steps. A
      database of 115,447 inpatients stays from 6 hospitals, and 236 ADE detection
      rules are used. Step 1: the patients differ significantly between and within
      hospitals, regarding their medical background, their medication and several
      outcomes. Step 2: The estimated ADE rates vary between and within hospitals. Step
      3: even when comparable conditions are present, the probability of ADE occurrence
      may differ between and within hospitals. Those 3 steps demonstrate that
      contextualization is necessary, and pave the way for a statistics-based method to
      contextualize ADE prevention (CDSS) and ADE detection tools.

PMID- 22874296
TI  - Identifying types and causes of errors in mortality data in a clinical registry
      using multiple information systems.
AB  - Errors may occur in the registration of in-hospital mortality, making it less
      reliable as a quality indicator. We assessed the types of errors made in in
      hospital mortality registration in the clinical quality registry National
      Intensive Care Evaluation (NICE) by comparing its mortality data to data from a
      national insurance claims database. Subsequently, we performed site visits at
      eleven Intensive Care Units (ICUs) to investigate the number, types and causes of
      errors made in in-hospital mortality registration. A total of 255 errors were
      found in the NICE registry. Two different types of software malfunction accounted
      for almost 80% of the errors. The remaining 20% were five types of manual
      transcription errors and human failures to record outcome data. Clinical
      registries should be aware of the possible existence of errors in recorded
      outcome data and understand their causes. In order to prevent errors, we
      recommend to thoroughly verify the software that is used in the registration
      process.

PMID- 22874297
TI  - Implementation of Computerized Physician Order Entry (CPOE) with Clinical
      Decision Support (CDS) features in Riyadh Hospitals to improve quality of
      information.
AB  - In this paper, we have conducted a preliminary study of the applied Clinical
      Decision Support (CDS) features in adopted Computerized Physician Order Entry
      (CPOE) systems. The study was conducted in three hospitals in Riyadh, the capital
      city of Saudi Arabia. The results show that the adoption of CPOE with a Clinical
      Decision Support System (CDSS) is not yet mature. CPOE systems allow physicians
      to enter their medication orders electronically, but many of the applied CPOE
      systems do not contain alerts to advise physicians of potentially dangerous
      interactions caused by incorrect medications. Hospitals are advised to enhance
      the role of CDSS with the CPOE to reduce medication errors, improve patients'
      safety and increase information quality.

PMID- 22874298
TI  - Information-based sequential selection of clinical tests in risk assessment.
AB  - We present a new framework for supporting decisions in sequential clinical risk
      assessment examinations. In this framework, the decision whether to perform a
      test depends on its expected contribution to risk assessment, given results of
      previous tests, and the contribution is quantified using information theory. In
      many cases adding an additional examination clearly improves the predictive
      model. However, there are cases in which the improvement is not constant for all
      values of previous tests, and quantification of possible improvement can support
      decision on further examinations. Using this approach can prevent many expensive,
      unpleasant or risky examinations. We demonstrate the use of this method on an
      example of type 2 diabetes onset study. The results show that reducing a
      considerable percent of the blood tests does not decrease the model's prediction
      power.

PMID- 22874299
TI  - Using EHR data for monitoring and promoting patient safety: reviewing the
      evidence on trigger tools.
AB  - Trigger tools, both paper and automated, have been viewed as a promising
      technology for patient record content analysis and identification of patient
      safety adverse events. The requirements and potential barriers for implementation
      of each line of tools have been explored by means of a literature review focusing
      on two interconnected subject areas: the Institute of Healthcare Improvement's
      paper-based Global Trigger Tool, which is currently taken up by several national
      level patient safety programs, and automated trigger tools, because of their
      increased feasibility as electronic health record (EHR) adoption grows. This
      paper provides an overview of the existing evidence on the strengths and
      weaknesses of each approach, and discusses the implications of the findings from
      the perspectives of healthcare organizations' management and staff, and from the
      viewpoint of demands on EHR systems.

PMID- 22874301
TI  - Architectural approach for quality and safety aware healthcare social networks.
AB  - Quality of information and privacy and safety issues are frequently identified as
      main limitations to make most benefit from social media in healthcare. The
      objective of the paper is to contribute to the analysis of healthcare social
      networks (SN), and online healthcare social network services (SNS) by proposing a
      formal architectural analysis of healthcare SN and SNS, considering the
      complexity of both systems, but stressing on quality, safety and usability
      aspects. Quality policies are necessary to control the quality of content
      published by experts and consumers. Privacy and safety policies protect against
      inappropriate use of information and users responsibility for sharing
      information. After the policies are established and documented, a proof of
      concept online SNS supporting primary healthcare promotion is presented in the
      paper.

PMID- 22874302
TI  - Human rights monitoring in virtual community.
AB  - Holistic disability rights monitoring is essential in order to translate rights
      on paper into rights in reality for people with disabilities. At the same time,
      evidence-based knowledge produced through holistic monitoring has to be made
      accessible to a broad range of groups - researchers, representatives of
      disability community, people with disabilities, the media, policy makers, general
      public - and also has to contribute to building capacity within disability
      community around human rights issues. This article focuses on the design process
      of a complex Virtual Knowledge Network (VKN) as an operational tool to support
      mobilization and dissemination of evidence-based knowledge produced by the
      Disability Rights Promotion International Canada (DRPI-Canada) project. This tool
      is embedded in the more general framework of the project grounded in a human
      rights approach to disability and that acknowledges the importance of creating
      knowledgeable communities in order to make the disability rights monitoring
      efforts sustainable, advancing thus the decision making process in Canada in
      order to enhance the quality of life of people with disabilities.

PMID- 22874303
TI  - Impact of the social networking applications for health information management
      for patients and physicians.
AB  - Most social network users hold more than one social network account and utilize
      them in different ways depending on the digital context. For example, friendly
      chat on Facebook, professional discussion on LinkedIn, and health information
      exchange on PatientsLikeMe. Thus many web users need to manage many disparate
      profiles across many distributed online sources. Maintaining these profiles is
      cumbersome, time consuming, inefficient, and leads to lost opportunity. In this
      paper we propose a framework for multiple profile management of online social
      networks and showcase a demonstrator utilising an open source platform. The
      result of the research enables a user to create and manage an integrated profile
      and share/synchronise their profiles with their social networks. A number of use
      cases were created to capture the functional requirements and describe the
      interactions between users and the online services. An innovative application of
      this project is in public health informatics. We utilize the prototype to examine
      how the framework can benefit patients and physicians. The framework can greatly
      enhance health information management for patients and more importantly offer a
      more comprehensive personal health overview of patients to physicians.

PMID- 22874304
TI  - Mobile Social Networking Health (MSNet-Health): beyond the mHealth frontier.
AB  - The purpose of this conceptual paper is to introduce the concept of Mobile Social
      Networking Healthcare (MSNet-Health). The paper defines MSNet-Health and provides
      a working scenario of MSNet-Health. The paper suggests various potential domain
      area applications for MSNet-Health, such as diabetes, antenatal education,
      smoking cessation, weight loss, and arthritis. Challenges and future research
      areas are also discussed.

PMID- 22874305
TI  - On the support of flexible patient privacy policies in social-medical discovery.
AB  - Many new socially flavored medical services have recently emerged, utilizing the
      data openness and sharing through social channels. The adoption of such services
      by patients is still very limited, mainly due to privacy issues. Existing social
      medical discovery services support only strict patient privacy policies and are
      not flexible enough to accommodate a wider range of privacy policy definitions.
      In this paper we present the IBM Medical Information and Care System (Medics)
      privacy-aware social-medical discovery solution that provides a highly flexible
      support for both fine-grained and dynamic patient privacy policies.

PMID- 22874306
TI  - Technical requirements of a social networking platform for senior citizens.
AB  - Feeling an integrative part of a social community adds to the quality of life.
      Elderly people who find it more difficult to actively join activities are often
      threatened by isolation. Social networking can enable communication and sharing
      activities makes it easier to set up and maintain contacts. This paper describes
      the development of a social networking platform and activities like gaming and
      exergaming all of which aim to facilitate social interaction. It reports on the
      particular challenges that need to be addressed when creating a social networking
      platform specially designed to meet the needs of the elderly.

PMID- 22874307
TI  - A real-time disease surveillance architecture using social networks.
AB  - In this paper we proposed surveillance architecture to track diseases-related
      postings in social networks using Twitter. In each part of the second, the real
      time architecture tracks status updates of people as they are posted as soon as
      possible. Data mining techniques will be used synchronically to crawl, index,
      extract and classify postings. This work is a part of constructing a global real
      time framework for early monitoring diseases outbreaks in social networks.

PMID- 22874308
TI  - Experiences in the creation of an electromyography database to help hand
      amputated persons.
AB  - Currently, trans-radial amputees can only perform a few simple movements with
      prosthetic hands. This is mainly due to low control capabilities and the long
      training time that is required to learn controlling them with surface
      electromyography (sEMG). This is in contrast with recent advances in
      mechatronics, thanks to which mechanical hands have multiple degrees of freedom
      and in some cases force control. To help improve the situation, we are building
      the NinaPro (Non-Invasive Adaptive Prosthetics) database, a database of about 50
      hand and wrist movements recorded from several healthy and currently very few
      amputated persons that will help the community to test and improve sEMG-based
      natural control systems for prosthetic hands. In this paper we describe the
      experimental experiences and practical aspects related to the data acquisition.

PMID- 22874309
TI  - Exploring the community structure of a diabetes forum.
AB  - A health forum is a kind of social network where users share information for
      specific topics they create. The purpose of this study was the identification of
      the key actors and the user communities in such a network. We used the publicly
      available data from a diabetes forum to create the corresponding network and
      explore several algorithms for the detection of user communities. The degree
      centrality of the network followed the power law distribution demonstrating that
      only a few users were the key actors in the forum. It was also shown that it is
      feasible to infer the top communities from a forum using certain algorithms; the
      key actors participated in these communities. Our approach could be applied to
      other health forums and be extended to examine additional aspects.

PMID- 22874310
TI  - Leveraging social media for preventive care-A gamification system and insights.
AB  - Patient compliance is an important factor in improving health outcomes. However,
      due to deferred benefits of treatment or lifestyle recommendations, patients
      often fail to comply with their medication, therapy or simply exercise or diet
      advice given by care providers until their health conditions deteriorate. As poor
      adherence remains a significant yet inadequately addressed health issue, it is
      critical to create effective interventions as part of the solutions. Previous
      studies indicate that peer supporting and social gaming can be useful for
      improving compliance. To understand how different motivation factors affect user
      behavior through social media, a healthcare compliance website with built-in
      behavior analyses was constructed to conduct experiments. Users' health
      compliance levels can be reported to the website and shared among consenting
      social members for discussion or competition. The theoretic models for behavior
      analyses include Maslow's hierarchy of needs and psychological game theory. The
      preliminary analysis showed that people using social media for healthcare
      compliance may be motivated differently and act strategically during their social
      interactions.

PMID- 22874311
TI  - Online health information search: what struggles and empowers the users? Results
      of an online survey.
AB  - The most popular mean of searching for online health content is a general search
      engine for all domains of interest. Being general implies on one hand that the
      search engine is not tailored to the needs which are particular to the medical
      and on another hand that health domain and health-specific queries may not always
      return adequate and adapted results. The aim of our study was to identify
      difficulties and preferences in online health information search encountered by
      members of the general public. The survey in four languages was online from the
      9th of March until the 27th of April, 2011. 385 answers were collected,
      representing mostly the opinions of highly educated users, mostly from France and
      Spain. The most important characteristics of a search engine are relevance and
      trustworthiness of results. The results currently retrieved do not fulfil these
      requirements. The ideal representation of the information will be a
      categorization of the results into different groups. Medical
      dictionaries/thesauruses, suggested relevant topics, image searches and spelling
      corrections are regarded as helpful tools. There is a need to work towards better
      customized solutions which provide users with the trustworthy information of high
      quality specific to his/her case in a user-friendly environment which would
      eventually lead to making appropriate health decisions.

PMID- 22874312
TI  - Finding online health-related information: usability issues of health portals.
AB  - As Internet and computers become widespread, health portals offering online
      health-related information become more popular. The most important point for
      health portals is presenting reliable and valid information. Besides, portal
      needs to be usable to be able to serve information to users effectively. This
      study aims to determine usability issues emerging when health-related information
      is searched on a health portal. User-based usability tests are conducted and eye
      movement analyses are used in addition to traditional performance measures.
      Results revealed that users prefer systematic, simple and consistent designs
      offering interactive tools. Moreover, content and partitions needs to be shaped
      according to the medical knowledge of target users.

PMID- 22874313
TI  - How medical doctors and students should use Social Media: a review of the main
      guidelines for proposing practical recommendations.
AB  - Social Media has grown exponentially and in the last few years there has been an
      increasing use amongst medical doctors and students. There is intense debate
      about the complexities of ensuring medical professionalism in the digital age and
      especially on using open and massive online services. The objectives of this
      paper are: first, to gather the main recommendations on using Social Media
      platforms and websites by medical doctors and students, which are proposed by
      several international organizations, institutions and universities of reference
      and second, to propose a set of practical recommendations, based on the
      comparison of the statements and items of the guidelines, in order to find
      agreements and differences among them and select the most common and practical
      items stated. A Decalogue of good practices has been drawn up, pointing out the
      most important aspects that should be considered, highlighting the relevance of
      maintaining professional behavior in these environments, taking into account the
      advantages and drawbacks when using them.

PMID- 22874314
TI  - Tracking changes in search behaviour at a health web site.
AB  - Nowadays, the internet is used as a means to provide the public with official
      information on many different topics, including health related matters and care
      providers. In this work we have studied a search log from the official Swedish
      health web site 1177.se for patterns of search behaviour over time. To improve
      the analysis, we mapped the queries to UMLS semantic types and MeSH categories.
      Our analysis shows that, as expected, diseases and health care activities are the
      ones of most interest, but also a clear increased interest in geographical
      locations in the setting of health care providers. We also note a change over
      time in which kinds of diseases are of interest. Finally, we conclude that this
      type of analysis may be useful in studies of what health related topics matter to
      the public, but also for design and follow-up of public information campaigns.

PMID- 22874315
TI  - Trustworthiness and relevance in web-based clinical question answering.
AB  - Question answering systems try to give precise answers to a user's question posed
      in natural language. It is of utmost importance that the answers returned are
      relevant to the user's question. For clinical QA, the trustworthiness of answers
      is another important issue. Limiting the document collection to certified
      websites helps to improve the trustworthiness of answers. On the other hand,
      limited document collections are known to harm the relevancy of answers. We show,
      however, in a comparative evaluation, that promoting trustworthiness has no
      negative effect on the relevance of the retrieved answers in our clinical QA
      system. On the contrary, the answers found are in general more relevant.

PMID- 22874317
TI  - A culture and power perspective on the management of health information
      technology in hospitals.
AB  - The three traditionally dominating professional hospital cultures - physicians,
      nurses and management - are challenged by the increasing use of health
      information technology (HIT) in health care. A fourth group of actors, the IT
      professionals has become an exceedingly powerful player challenging the
      boundaries of the traditional hospital cultures. The hospital cultures are being
      redefined by and are redefining the technologies as well as the divisions of
      labour between the professional groups. The IT-professionals have become central
      actors in this and thereby they constitute a fourth powerful professional culture
      in the hospitals. This study draws out the phenomenon of IT-professionals as a
      fourth culture through a qualitative case study of both the IT-department and
      clinical and managerial hospital practices. The study finds evidence of how the
      IT-professionals and the IT-departments play a central part in the development of
      hospital practices constituting them as an influential culture and player in the
      hospitals. The tendency to see IT as merely infrastructure is hereby challenged
      and the conclusions demand further research into how to consider IT strategically
      in the hospitals, possibly pointing towards further user involvement in IT
      management.

PMID- 22874318
TI  - Economic impact of a nationwide interoperable e-Health system using the PENG
      evaluation tool.
AB  - OBJECTIVE: The aim of this paper is to evaluate the costs and benefits of the
      Estonian interoperable health information exchange system. In addition, a
      framework will be built for follow-up monitoring and analysis of a nationwide HIE
      system. METHODS: PENG evaluation tool was used to map and quantify the costs and
      benefits arising from type II diabetic patient management for patients, providers
      and the society. The analysis concludes with a quantification based on real costs
      and potential benefits identified by a panel of experts. RESULTS: Setting up a
      countrywide interoperable eHealth system incurs a large initial investment.
      However, if the system is working seamlessly, benefits will surpass costs within
      three years. The results show that while the society stands to benefit the most,
      the costs will be mainly borne by the healthcare providers. Therefore, new
      government policies should be devised to encourage providers to invest to ensure
      society wide benefits.

PMID- 22874319
TI  - How should we define eHealth, and does the definition matter?
AB  - There is no useful definition for eHealth; we would like to find one. This study
      will provide a contribution to clarify the discussion on eHealth as a concept to
      enhance the understanding of the range of meanings which have been ascribed to
      the term ehealth.

PMID- 22874320
TI  - Medical device software: a new challenge.
AB  - The application of software in the medical device domain has become central to
      improve diagnoses and treatments. The introduction of new regulations poses
      issues for the qualification and classification of MD software and requires
      complex procedures to make them complaint with safety requirements. The paper
      focuses on EU, Canada and US regulations, standards and guidelines and in
      particular highlights the integration of the risk management process with the
      software lifecycle.

PMID- 22874321
TI  - The intellectual property management for data sharing in a German liver cancer
      research network.
AB  - Sharing data in biomedical research networks has great potential benefits
      including efficient use of resources, avoiding duplicate experiments and
      promoting collaboration. However, concerns from data producers about difficulties
      of getting proper acknowledgement for their contributions are becoming obstacles
      for efficient and network wide data sharing in reality. Effective and convenient
      ways of intellectual property management and acknowledging contributions to the
      data producers are required. This paper analyzed the system requirements for
      intellectual property management in a German liver cancer research network and
      proposed solutions for facilitating acknowledgement of data contributors using
      informatics tools instead of pure policy level strategies.

PMID- 22874322
TI  - The nature of unintended benefits in health information systems.
AB  - Health information systems (HISs) have been shown to introduce unintended
      consequences post implementation. Much of the current research on these
      consequences has focused on the negative aspects of them. However unintended
      consequences of HIS usage can also be beneficial to various aspects of healthcare
      delivery. This paper uses several case studies of HIS implementation to develop a
      model of unintended benefits of HIS usage with three categories of benefits:
      patient, service delivery and administrative. We also discuss the implications of
      these benefits on the design and evaluation of HISs.

PMID- 22874323
TI  - Envisioning electronic health record systems as change management: the experience
      of an English hospital joining the National Programme for Information Technology.
AB  - The historical National Programme for Information Technology (NPfIT) in England
      was the most expensive (~$20billion) and ambitious politically-driven IT-based
      transformations of public services ever undertaken. Nation-wide implementation of
      integrated electronic health record (EHR) systems in hospitals was at the heart
      of the NPfIT (~$10billion). We conducted the first longitudinal, prospective, and
      sociotechnical case study implementation and adoption of national EHRs
      implementations in 12 'early adopter' hospitals across England. This paper
      reports the arrival, implementation process, and stakeholders' experiences of one
      EHR software (Millennium) at a National Health Service's (NHS) general hospital
      participating in NPfIT, hereafter called Alpha. From the outset, Alpha envisioned
      the implementation of EHR as a practice of change management to improve its
      performance. This vision attributed to the establishment of a 'design authority'
      at Alpha, including users from various capacities and levels. The 'design
      authority' was perceived a key contributor to appropriate (compared to other
      hospitals we studied) clinical engagement and bottom-up approach to deploying
      EHR. Through conducting several hundreds of group and individual workflow
      familiarization, Alpha adopted a novel approach to training staff on EHR
      software. This led to greater local configuration and high sense of ownership
      among users, which transformed work practices towards overall better performance
      of the hospital. Contrary to painful and turbulent experiences of EHR
      implementation via NPfIT route in the English hospitals, this in-depth case study
      revealed the importance of vision (change management) and insightful leadership
      in 'working out' EHR. We advocate envisioning EHRs as change management endeavors
      to enhance their complex, multi-dimensional, and sociotechnical adoption in
      healthcare settings.

PMID- 22874324
TI  - Method for modeling social care processes for national information exchange.
AB  - Finnish social services include 21 service commissions of social welfare
      including Adoption counselling, Income support, Child welfare, Services for
      immigrants and Substance abuse care. This paper describes the method used for
      process modeling in the National project for IT in Social Services in Finland
      (Tikesos). The process modeling in the project aimed to support common national
      target state processes from the perspective of national electronic archive,
      increased interoperability between systems and electronic client documents. The
      process steps and other aspects of the method are presented. The method was
      developed, used and refined during the three years of process modeling in the
      national project.

PMID- 22874325
TI  - On the attitudes of GPs toward novel features of their next EPRs.
AB  - In this paper we report the findings from a CATI-based survey that involved a
      representative sample of General Practitioners in Italy. Respondents were asked
      about their use of ICT in keeping in touch with their patients; their adoption
      and actual use of their Electronic Patient Record (EPR); and, more importantly,
      their perception of usefulness of a series of novel functionalities that could
      enrich the next generation of EPR in general practice.

PMID- 22874326
TI  - Proposal of an architecture for the national integration of Electronic Health
      Records: a semi-centralized approach.
AB  - This paper proposes a novel architecture for the national integration of
      Electronic Health Records (EHRs), the semi-centralized approach, in which
      summarized EHRs are maintained centrally at a nation-wide system with references
      to their comprehensive versions at their original locations on the various
      healthcare providers' databases. The idea is to allow the clinicians to have an
      idea of what is included inside the patient's EHRs at each healthcare provider's
      database and to have a general view of the patient's medical history, and when
      needed to retrieve the complete EHR of the patient from a remote healthcare
      providers' systems. A high level system architecture needed to integrate EHRs
      from various sources on a nation-wide basis using the proposed semi-centralized
      approach is described. Best practices and essential requirements are the central
      to the evolution of the approach taken.

PMID- 22874327
TI  - Uniforming information management in Finnish Social Welfare.
AB  - This paper describes the phases and methods used in the National project for IT
      in Social Services in Finland (Tikesos). The main goals of Tikesos were to unify
      the client information systems in social services, to develop electronic
      documentation and to produce specifications for nationally organized electronic
      archive. The method of Enterprise Architecture was largely used in the project.

PMID- 22874329
TI  - Assessment in health care education - modelling and implementation of a computer
      supported scoring process.
AB  - Research on computer supported scoring of assessments in health care education
      has mainly focused on automated scoring. Little attention has been given to how
      informatics can support the currently predominant human-based grading approach.
      This paper reports steps taken to develop a model for a computer supported
      scoring process that focuses on optimizing a task that was previously undertaken
      without computer support. The model was also implemented in the open source
      assessment platform TAO in order to study its benefits. Ability to score test
      takers anonymously, analytics on the graders reliability and a more time
      efficient process are example of observed benefits. A computer supported scoring
      will increase the quality of the assessment results.

PMID- 22874330
TI  - eHealth education of professionals in the Baltic Sea Area.
AB  - In this paper we present a study on the extent, level and content of e-Health in
      existing formal educational systems in Lithuania, Germany, Finland, Norway and
      Denmark with the objectives of identifying future educational needs within this
      area. The study was carried out as a desk-top study and took place within the
      context of the ICT for Health project. The results of the study on the one hand
      revealed a wide range of programs and courses that included e-Health, but on the
      other hand also showed that in the educations of health care professionals
      (physicians, nurses etc.) the integration of e-Health elements are often marginal
      or non-existing. Thus the study indicates that there is a need for a higher
      integration of e-Health in the education of health care professionals. We discuss
      what kind of knowledge of e-Health is needed and how it could or should be
      integrated in these educations. We argue that providing possibilities for
      applying and experimenting with e-Health system in a concrete and tangible manner
      is central in order to raise the acceptance and capabilities of health care
      professionals to use e-Health systems.

PMID- 22874331
TI  - Is it worth investing in online continuous education for healthcare staff?
AB  - Educational activities for hospital staff don't easily match with the congestive
      rhythm of healthcare personnel working life. Online learning could make it easier
      for healthcare personnel to attend courses, but there is still uncertainty about
      the feasibility of using distance learning to effectively meet education goals in
      healthcare institutions. Fondazione Salvatore Maugeri (FSM) started an online
      educational program, as pilot project, in October 2010. The present study hence
      is aimed at evaluating the impact of this initiative (in terms of extent and
      intensity of healthcare staff attendance; objective and subjective effectiveness)
      in order to take informed decisions for the future. In 15 months, 5 elearning
      courses have been provided to 2261 potential users of 14 FSM hospitals, in
      parallel with traditional education. 1099 users from all the hospital have
      intensively attended the courses (58% of nurses, 50% of therapists, 44%, of
      technicians, 25% of physicians) for a total of 27459 CME credits. Effectiveness
      in terms of knowledge gain is satisfactory and subjective evaluation is good
      (more than 95% of satisfied users). Elearning is not appropriate for all the
      educational needs and is not a panacea, but the reported results point out that
      it may be an effective and economically convenient mean to support massive
      educational interventions reaching results hardly attainable with traditional
      education. Users should be better educated about how to exploit online education
      at best.

PMID- 22874332
TI  - Nursing informatics competences still challenging nurse educators.
AB  - In recent years nursing documentation has been one of the most important
      development areas of nursing informatics (NI) in Finland. The purpose of this
      study is to describe the development of the nurse educators' competences in
      nursing documentation during a project called eNNI. The eNNI project (2008-2010)
      was a cooperative project by nurse educators and working life experts. The goal
      of the project was to implement the national documentation model and thereby
      improve operational processes at workplaces. The study includes pre- and post
      test questioning of NI applications with a web-based questionnaire (n=136). The
      data were analyzed with distribution, cross-tabulations and average tests and
      descriptive statistic multivariate method. According to the results, the ICT
      skills of the nurse educators were good at the end of the project, and they had
      good information literacy competence. On the other hand, their advanced NI skills
      left room for improvement.

PMID- 22874333
TI  - Teaching medicine with a terminology/ontology portal.
AB  - The Health Terminology/Ontology Portal (HeTOP) was developed to provide easy
      access to health terminologies and ontologie. The repository is not only
      dedicated to professionals but is also a valuable teaching tool. Currently, it
      provides access to thirty two health terminologies and ontologies available
      mainly in French or in English, but also in German, Italian, Chinese, etc. HeTOP
      can be used by both humans and computers via Web services. To integrate new
      resources into HeTOP, three steps are necessary: (1) designing a meta-model into
      which each terminology (or ontology) can be integrated, (2) developing a process
      to include terminologies into HeTOP, (3) building and integrating existing and
      new inter & intra-terminology semantic harmonization into HeTOP. Currently, 600
      unique machines use the MeSH version of HeTOP every day and restricted
      terminologies/ontologies are used for teaching purposes in several medical
      schools in France. The multilingual version of HeTOP is available (URL:
      http://hetop.eu/) and provides free access to ICD10 and FMA in ten languages.
      CONCLUSION: HeTOP is a rich tool, useful for a wide range of applications and
      users, especially in education and resource indexing but also in information
      retrieval or performing audits in terminology management.

PMID- 22874334
TI  - Criteria to assess the quality of virtual patients.
AB  - Quality assessment of virtual patients (VP) is important but still insufficiently
      standardized. We developed categories and criteria to assess the quality of
      virtual patients. These categories reflect the life cycle of a VP from the
      planning to the development, implementation and evaluation. Such elaborated
      criteria will help authors to create VPs and curriculum planners to assess the
      quality of implemented VPs and choose high quality VPs from repositories.

PMID- 22874335
TI  - New approaches to linking clinical guidelines to virtual patients.
AB  - An often reported challenge of evidence-based medicine concerns increasing use of
      clinical guidelines in practice. One of the proposed improvements is to promote
      guidelines by presenting them in conjunction with virtual patients. Three
      approaches to linking clinical guidelines to virtual patients are presented in
      this paper: (1) guidelines as a source for generating virtual patients; (2)
      guidelines hyper-flowchart as a virtual patient progress indicator; (3)
      guidelines flowchart reconstruction as a learning activity in virtual patient
      systems. The scenarios have been preliminarily evaluated using two demonstrator
      applications: Bit Pathways and CASUS. Challenges and direction for further
      development are proposed.

PMID- 22874336
TI  - Recommendation of standardized health learning contents using archetypes and
      semantic web technologies.
AB  - Linking Electronic Healthcare Records (EHR) content to educational materials has
      been considered a key international recommendation to enable clinical engagement
      and to promote patient safety. This would suggest citizens to access reliable
      information available on the web and to guide them properly. In this paper, we
      describe an approach in that direction, based on the use of dual model EHR
      standards and standardized educational contents. The recommendation method will
      be based on the semantic coverage of the learning content repository for a
      particular archetype, which will be calculated by applying semantic web
      technologies like ontologies and semantic annotations.

PMID- 22874337
TI  - SIScaR-GPU: fast simulation and visualization of intraoperative scattered
      radiation to support radiation protection training.
AB  - Scattered radiation caused by the intraoperative use of mobile image intensifier
      systems (referred to as "C-arms") is the main source of radiation exposure for
      operating room personnel and surgeons. To keep this possibly harmful exposure at
      a minimum level, a deliberate use of radiation, knowledge about distribution of
      scattered radiation and appropriate behavior pattern are indispensable. Therefore
      in several countries knowledge concerning these aspects is taught in mandatory
      courses on radiation protection. Currently this teaching is typically based on
      non-interactive didactical methods (texts, pictures and videos). Because of the
      complexity of the knowledge field this restriction might lead to an insufficient
      understanding of the facts, an inappropriate behavior and therefore to an
      avoidable radiation exposure. This paper presents a new software module, which is
      able to simulate and visualize intraoperative radiation distribution and the
      resulting dose values for the attending persons within a few seconds (less than
      30s). The developed components, which simulate the radiation transport using a
      graphics processing unit three times faster than comparable approaches, were
      integrated exemplarily in the computer based C-arm training system virtX. This
      extended training system improves the teaching through a prompt visual feedback
      on non-trivial scattered radiation facts in freely adoptable situations.

PMID- 22874338
TI  - Towards a mLearning training solution to the adoption of a CPOE system.
AB  - Computerized Physician Order Entry (CPOE) has been introduced as a solution that
      can fundamentally change the way healthcare is provided, affecting all types of
      healthcare stakeholders and improving healthcare decisions, patient outcomes,
      patient safety and efficiency. However, a relatively small proportion of
      healthcare organizations have implemented CPOE systems, due to its technological
      complexity and to its low acceptance rate by healthcare professionals who largely
      disregard the value of CPOE in efficient healthcare delivery. An online training
      facility embedded within a CPOE service may increase the likelihood of its
      adoption by healthcare professionals as it offers them guidelines on how to
      perform each task of the CPOE service. In contrast to CPOE, on the other hand,
      handheld devices and other mobile technologies have showed an increased adoption
      rate. This paper considers a CPOE service that can be accessed by authorized
      healthcare professionals through their mobile devices anytime anywhere, and
      allows embedded training content, which has been developed through a learning
      management system (LMS) to be presented to the user automatically upon request.

PMID- 22874339
TI  - Virtual patient simulation: a comparison of two approaches for capacity building
      in Sub-Saharan Africa.
AB  - BACKGROUND: given the diversity of virtual patient simulation systems, this study
      provides a comparison of two different tools, in the perspective of deploying
      them for supporting initial and continuing medical education in Sub-Saharan
      Africa. METHOD: the evaluation was based on existing documentation, analysis of
      the data models, usage of implemented of virtual patient cases, and interviews
      with the domain experts. RESULTS: despite some shared similarities in their
      contents, there are many differences between the two applications especially in
      respect to their pedagogic models, technical architecture, types of interactions,
      feedback, and the learner's performance evaluations. DISCUSSION AND CONCLUSION:
      the implementation of learning activity based on virtual patient in a given
      context should consider these differences. According to their respective
      approaches, this study suggests that MVP is more suitable for novice learners
      whereas VIPS is more suitable for experienced learners.

PMID- 22874341
TI  - An integration of Emergency Department Information and Ambulance Systems.
AB  - In this paper we propose an Emergency Department Information System that will be
      integrated with the ambulance system to improve the communication, enhance the
      quality of provided emergency services and facilitate information sharing. The
      proposed system utilizes new advanced technologies such as mobile web services
      that overcome the problems of interoperability between different systems, HL7 and
      GPS. The system is unique in that it allows ambulance officers to locate the
      nearest specialized hospital and allows access to the patient's electronic health
      record as well as providing the hospital with required information to prepare for
      the incoming patient.

PMID- 22874342
TI  - Analyzing primary care data to characterize inappropriate emergency room use.
AB  - Primary care data represents the complete biopsychosocial profile of the patient
      and has recently become available for secondary analysis in Ontario. This study
      involved extracting de-identified primary care data and analyzing it with natural
      language processing to extract UMLS codes. These codes were used to statistically
      relate inappropriate emergency room use to biopsychosocial concepts with logistic
      regression. The concepts of pain and mental health were statistically
      significant. This technique demonstrates a creative use of primary care data. It
      could be used to analyze system use in other health care settings.

PMID- 22874343
TI  - COCPIT: a tool for integrated care pathway variance analysis.
AB  - Electronic Health Record (EHR) data has the potential to track patients' journeys
      through healthcare systems. Many of those journeys are supposed to follow
      Integrated Care Pathways (ICPs) built on evidence based guidelines. An ICP for a
      particular condition sets out "what should happen", whereas the EHR records "what
      did happen". Variance analysis is the process by which the difference between
      expected and actual care is identified. By performing variance analysis over
      multiple patients, patterns of deviation from idealised care are revealed. The
      use of ICP variance analysis, however, is not as widespread as it could be in
      healthcare quality improvement processes - we argue that this is due to the
      difficulty of combining the required specialist knowledge and skills from
      different disciplines. COCPIT (Collaborative Online Care Pathway Investigation
      Tool) was developed to overcome this difficulty and provides clinicians and
      health service managers with a web-based tool for Care Pathway Variance Analysis.

PMID- 22874344
TI  - Flexible medical image management using service-oriented architecture.
AB  - Management of medical images increasingly involves the need for integration with
      a variety of information systems. To address this need, we developed Content
      Management Offering (CMO), a platform for medical image management supporting
      interoperability through compliance with standards. CMO is based on the
      principles of service-oriented architecture, implemented with emphasis on three
      areas: clarity of business process definition, consolidation of service
      configuration management, and system scalability. Owing to the flexibility of
      this platform, a small team is able to accommodate requirements of customers
      varying in scale and in business needs. We describe two deployments of CMO,
      highlighting the platform's value to customers. CMO represents a flexible
      approach to medical image management, which can be applied to a variety of
      information technology challenges in healthcare and life sciences organizations.

PMID- 22874345
TI  - Measuring health care process quality with software quality measures.
AB  - Existing quality models focus on some specific diseases, clinics or clinical
      areas. Although they contain structure, process, or output type measures, there
      is no model which measures quality of health care processes comprehensively. In
      addition, due to the not measured overall process quality, hospitals cannot
      compare quality of processes internally and externally. To bring a solution to
      above problems, a new model is developed from software quality measures. We have
      adopted the ISO/IEC 9126 software quality standard for health care processes.
      Then, JCIAS (Joint Commission International Accreditation Standards for
      Hospitals) measurable elements were added to model scope for unifying functional
      requirements. Assessment (diagnosing) process measurement results are provided in
      this paper. After the application, it was concluded that the model determines
      weak and strong aspects of the processes, gives a more detailed picture for the
      process quality, and provides quantifiable information to hospitals to compare
      their processes with multiple organizations.

PMID- 22874346
TI  - Bringing research to the point of care: Hypergenes project study.
AB  - With advance of health information IT systems and increasing volumes of disparate
      biomedical information repositories, harvesting them for research purposes is
      becoming more difficult. This is partly due to the proprietary nature of the
      current systems, but also due to diverse requirements of different research
      paradigms. On the flip side, ever larger amounts of clinical and genomic data are
      currently accumulated in research projects. Tapping into these research silos
      would not only contribute to further research, but could help convey timely
      information to clinicians at the point of care. This paper presents RIMon - a
      portal-based infrastructure for information-intensive research cycle as used in
      the Hypergenes project, which aims at building a method to dissect complex
      genetic traits using essential hypertension as a disease model. RIMon allows
      users to: (a) collect data from points of care, (b) query and retrieve collected
      data for analysis, (c) query accumulated information and knowledge to construct
      disease models based on analysis results, and (d) to eventually make the research
      results readily available to the clinicians at the point of care. This
      translational cycle is demonstrated in the Hypergenes project along with a
      potential usage scenario.

PMID- 22874347
TI  - Do worklists work? A quantitative approach to the assessment of an Electronic
      Patient Record function.
AB  - In this study, a quantitative approach was used to assess an Electronic Patient
      Record worklist function introduced to prevent radiology reports from being
      overlooked by the responsible clinicians. The function reduced the rate of
      overlooked reports, but was not able to eliminate it. Not all reports were
      identified by the automatic worklist function. Clinicians did not use the
      worklists to detect new reports. Our results suggest that this was not the result
      of insufficient user training or user errors, but rather that the worklists
      function did not comply with the way clinical work was organised and performed.
      Quantitative methods as used in this study are suggested as supplementary to the
      traditional qualitative methods.

PMID- 22874348
TI  - Log analysis to understand medical professionals' image searching behaviour.
AB  - This paper reports on the analysis of the query logs of a visual medical
      information retrieval system that provides access to radiology resources. Our
      analysis shows that, despite sharing similarities with general Web search and
      also with biomedical text search, query formulation and query modification when
      searching for visual biomedical information have unique characteristics that need
      to be taken into account in order to enhance the effectiveness of the search
      support offered by such systems. Typical information needs of medical
      professionals searching radiology resources are also identified with the goal to
      create realistic search tasks for a medical image retrieval evaluation benchmark.

PMID- 22874349
TI  - Ontology-supported clinical profiling for the evaluation of obesity and related
      comorbidities.
AB  - An ontology-supported e-knowledge base aimed to the evaluation of obesity and
      related co-morbidities is presented. The main goal of such a clinical profiling
      tool is to help determine the health status of a subject, supporting the
      knowledge transfer between medical researchers and general practitioners.

PMID- 22874350
TI  - Texture analysis software: integration with a radiological workstation.
AB  - Image analysis is the daily task of radiologists. The texture of a structure or
      imaging finding can be more difficult to describe than other parameters. Image
      processing can help the radiologist in completing this difficult task. The aim of
      this article is to explain how we have developed texture analysis software and
      integrated it into a standard radiological workstation. The texture analysis
      method has been divided into three steps: definition of primitive elements,
      counting, and statistical analysis. The software was developed in C++ and
      integrated into a Siemens workstation with a graphical user interface. The
      results of analyses may be exported in Excel format. The software allows users to
      perform texture analyses on any type of radiological image without the need for
      image transfer by simply placing a region of interest. This tool has already been
      used to assess the trabecular network of vertebra. The integration of such
      software into PACS extends the applicability of texture analysis beyond that of a
      mere research tool and facilitates its use in routine clinical practice.

PMID- 22874351
TI  - A smartphone application for preventing exercise-induced glycemic imbalances in
      type 1 diabetic patients.
AB  - Regular moderate-intensity physical activity is strongly recommended as well in
      patients with type 1 diabetes mellitus. However, the more frequent complication
      of exercise in T1DM patients is an excessive fall of glycaemia, which remains
      thus the strongest barrier to physical activity and the number of difficulties
      patients have to meet often further discourage them. Recently, a new algorithm
      has been proposed, that estimates, on a patient- and situation-specific basis,
      the amount of supplemental carbohydrates required by diabetic patients in order
      to exercise under safe blood glucose levels. The present paper discusses an
      implementation of the ECRES algorithm aimed at smartphones, and its preliminary
      evaluation from the accuracy point of view versus the original implementation, as
      well as usability. The developed mobile application replicates the original
      algorithm in a portable device that, after its preliminary experimentation, may
      be useful to make physical activity easier for diabetic patients.

PMID- 22874352
TI  - An Android-enabled mobile framework for ensuring quality of life through patient
      centric care.
AB  - The drive to achieve excellence in healthcare delivery while containing costs,
      underlies the need for a new generation of applications which facilitate the
      realization of a patient-centric care model. Under this emerging care model
      healthcare delivery can be integrated across the continuum of services, from
      prevention to follow up, and care can be coordinated across all settings. With
      care moving out into the community, health systems require real-time information
      to deliver coordinated care to patients. The integration of leading-edge
      technologies, such as mobile technology, with Personal Health Records (PHRs) can
      meet this requirement by making comprehensive and unified health information
      available to authorized users at any point of care or decision making through
      familiar environments such as Google's Android. This paper presents a framework
      that provides ubiquitous access to patients' PHRs via Android-enabled mobile
      devices. Where possible health information access and management is performed in
      a transparent way, thus enabling healthcare professionals to devote more time on
      practicing medicine and patients to manage their own health with the least
      possible intervention. This depends heavily on the context, which is collected by
      both Android-specific core system services and special purpose software agents
      with the latter being also responsible for preserving PHR data privacy.

PMID- 22874353
TI  - Model driven mobile care for patients with type 1 diabetes.
AB  - We gathered a data set from 30 patients with type 1 diabetes by giving the
      patients a mobile phone application, where they recorded blood glucose
      measurements, insulin injections, meals, and physical activity. Using these data
      as a learning data set, we describe a new approach of building a mobile feedback
      system for these patients based on periodicities, pattern recognition, and scale
      space trends. Most patients have important patterns for periodicities and trends,
      though better resolution of input variables is needed to provide useful feedback
      using pattern recognition.

PMID- 22874354
TI  - Personalized adherence activity recognition via model-driven sensor data
      assessment.
AB  - Creation of a personalized adherence feedback loop is crucial for initiating and
      sustaining health behavior change. However, self reports are not sufficient to
      measure actual adherence. Recording and recognizing personal activities in a
      ubiquitous environment has thus emerged as a promising solution. In this work, we
      present a model-driven sensor data assessment mechanism capable of identifying
      high level adherence-related activity patterns from low level signals. The
      proposed intelligent sensing algorithm can learn from a population-based training
      data set and adapt quickly to an individual's exercise patterns using the
      acquired personal data. Upon the recognition of each activity, the system can
      further provide personalized feedback such as exercise coaching, fitness
      planning, and abnormal event detection. The resulted system demonstrates the
      feasibility of a portable real-time personalized adherence feedback system that
      could be used for advanced healthcare services.

PMID- 22874355
TI  - Achieving IT-supported standardized nursing documentation through participatory
      design.
AB  - In the Capital Region of Denmark a full-scale pilot project on IT-supported
      nursing documentation is - after running for two months at one full university
      hospital - showing promising results. In this paper we discuss participatory
      design as a method to design clinical documentation templates that support
      guideline-based highly structured standard documentation in a large organization
      with many stakeholders. Applying a participatory design (PD) approach at many
      organizational levels has involved the stakeholders actively in the design
      process. Developing a set of design principles has concurrently made it possible
      to frame the discussions among the different stakeholders. Both PD and design
      principles have been instrumental in designing and implementing a set of standard
      templates that support the daily work and coordination between the nurses.

PMID- 22874356
TI  - Consistency of nurses' daily predictions of survival in the intensive care.
AB  - In the Intensive Care Unit, clinicians are continuously faced with the difficult
      task of prognosis, but their predictions of patient survival status may not
      always be consistent. Specifically very little is known about consistency of
      predictions over time. The aim of this paper is to assess the consistency of
      nurses' daily predictions of survival in terms of inter-observer variance and
      variance of observers over time. We found a low consistency of these predictions
      between observers and over time, even though changes in the patients' condition
      are considered. Our findings have implications to the process of end-of-life
      decision-making, which pertains to withholding or withdrawing intensive care
      treatment.

PMID- 22874357
TI  - Development of Pain flowsheet based on electronic nursing record system.
AB  - Pain assessment and control is the most important issue in medical fields. To
      manage patient pain effectively with high quality, we need a Pain flowsheet to
      share patient information of pain between staffs. Nurses already input more
      information into their electronic nursing record. We focus how to integrate each
      data and show appropriately without nurse's duplicated work. Finally we develop
      the Pain flowsheet based on nursing record, that includes the pattern of pain,
      influential factors, how to implement previously, what to do pain control. This
      study shows that well designed structured nursing records is an essential
      basement to advance medical process. In addition, we expect to develop more
      helpful functions through how to reorganize and combine each data.

PMID- 22874358
TI  - Electronic nursing documentation in a paediatrics hospital: impact on quality of
      care by using OpenEHR, IHE and HL7.
AB  - The acuity of illness of sick children requiring care in hospital is increasing.
      There are many more children now with disabilities and complicated long term
      illnesses. Respiratory illness is the commonest cause of morbidity in young
      children. Nurses have a pivotal role in the anticipation of and/or early
      identification of the sick child with potential or actual respiratory failure
      through the assessment and measurement of the child's pattern of breathing,
      including rate, rhythm and effort. It should also be conducted and interpreted in
      association with other clinical assessments, for example cardiovascular. Record
      keeping is an essential part of nursing care because it details the patient
      journey through the healthcare process. Good quality record keeping can improve
      the quality of patient care and for this reason nurses must seek to ensure that
      their documentation practices meet high standards. Poor standards of
      documentation were a contributory factor in the failure to detect patients who
      were clinically deteriorating. In this article we searched for evidence whether
      electronic health records has positive impact on quality of nursing care and
      present our experiences with electronic nursing documentation in the field of
      respiratory assessment of the children and young people.

PMID- 22874359
TI  - ICNP Catalogues for supporting nursing content in electronic health records.
AB  - The purpose of this study was to describe sets of nursing concepts including, for
      example, nursing diagnoses and interventions, which are knowledge-based and
      clinically relevant to support nursing practice. Health information systems using
      the International Classification for Nursing Practice (ICNP(r)) provide a
      platform for standardized nursing documentation for patients' health care,
      clinical decision support, and repositories for re-use of clinical data for
      quality evaluation, research, management decisions and policy development.
      Clinically relevant sets of ICNP concepts can facilitate implementation of health
      information systems for nursing. Descriptive analysis was used to examine the
      types of, and relationships among, existing nursing content sets. Findings
      included the need for various types of content sets, as represented in ICNP
      catalogues, for nursing documentation. Five types of ICNP Catalogues included
      Care Plans, Order Sets, Clinical Templates, Nursing Minimum Data Sets, and
      Terminology Subsets.

PMID- 22874360
TI  - INCA - Individual Nomad Clinical Assistant - supporting nurses with mobile
      devices.
AB  - INTRODUCTION: A completely structured nursing record has been deployed in the 8
      hospitals of the University hospitals of Geneva. Even with laptops, the access to
      the records restrains nurses' mobility during their bedside work. It has lead to
      a strong demand for mobile devices. PROBLEM: There are several papers showing
      that mobile computers can lead to increase time for data acquisition, increased
      errors and omissions. Thus, there are important challenges at developing these
      tools, while respecting the mobile paradigm and the needs for qualitative and
      efficient acquisition. A simple translation of user interfaces from usual
      computers is not recommended. RESULTS: After evaluating various user interfaces
      with users in real conditions, we propose a solution that eases the selection of
      patients, the navigation into the various screens, and provides a very clear list
      of tasks to achieve for nurses. CONCLUSION: The article exposes the difficulties
      to adapt an existing tool on mobile devices. Despite these difficulties, by
      organizing smartly the displayed information, we produced a tool with similar
      functionalities but better adapted to the user.

PMID- 22874362
TI  - A system-theoretical, architecture-based approach to ontology management.
AB  - Comprehensive interoperability between distributed eHealth/pHealth environments
      requires that the systems involved are based on a common architectural framework
      and share common knowledge. The paper deals with the representation of systems by
      related ontologies. Therefore, the architectural principles ruling the system
      design and the interrelations of its components also rule the design of those
      ontologies and their management as exemplified.

PMID- 22874363
TI  - Characteristics of health interventions: a systematic analysis of the Austrian
      Procedure Catalogue.
AB  - The Austrian Procedure Catalogue contains 1,500 codes for health interventions
      used for performance-oriented hospital financing in Austria. It offers a
      multiaxial taxonomy. The aim of this study is to identify characteristics of
      medical procedures. Therefore a definition analysis followed by a typological
      analysis was conducted. Search strings were generated out of code descriptions
      regarding the heart, large vessels and cardiovascular system. Their definitions
      were looked up in the Pschyrembel Clinical Dictionary and documented. Out of
      these definitions, types which represent characteristics of health interventions
      were abstracted. The three axes of the Austrian Procedure Catalogue were approved
      as well as new, relevant information identified. The results are the foundation
      of a further enhancement of the Austrian Procedure Catalogue.

PMID- 22874364
TI  - Describing the sublanguage of wound care in an adult ICU.
AB  - Comprehensive wound documentation is an important tool in evaluating and planning
      patient care. The sublanguage used in ICUs may affect negatively to the wound
      care and thus to the healing process. We made a quantitative content analysis of
      nursing documentation of cardiac surgery adult patients (n=60) who had stayed
      over four days in the ICU. The sublanguage used in nursing documentation of
      wounds and ulcers in the ICU was unstructured with many words of colloquial
      language, misspellings and abbreviations. The documentation did not cover all
      aspects of proper wound care. The information technology could be helpful for
      nurses to document right things with plain language.

PMID- 22874365
TI  - Developing a patient education method - the e-Knowledge Test with feedback.
AB  - Breast cancer and its treatment radiotherapy, have impact on woman's psychosocial
      and physical well-being causing disruption to quality of life. Because of the
      positive effects of knowledge on quality of life there is a challenge to develop
      effective education methods. Due to the growing use of internet among breast
      cancer patients the development should be focused on e-education. An e-education
      method, the e-Knowledge Test of radiotherapy with feedback for breast cancer
      patients (e-KTRT-BC) was planned and piloted. The content of it based on
      literature of breast cancer patients' knowledge needs of radiotherapy and
      structured through aspects of empowerment as a nursing intervention. The face
      validity study that was conducted via email revealed that the content of e-KTRC
      BC was easy to use and understand. The e-KTRT-BC could be used as an e-education
      method to meet the breast cancer patients' knowledge needs. Evaluating the
      empowering effect of patient e-education with feedback is important for further
      development of e-education methods.

PMID- 22874366
TI  - Representing clinical communication knowledge through database management system
      integration.
AB  - Clinical communication failures are considered the leading cause of medical
      errors [1]. The complexity of the clinical culture and the significant variance
      in training and education levels form a challenge to enhancing communication
      within the clinical team. In order to improve communication, a comprehensive
      understanding of the overall communication process in health care is required. In
      an attempt to further understand clinical communication, we conducted a thorough
      methodology literature review to identify strengths and limitations of previous
      approaches [2]. Our research proposes a new data collection method to study the
      clinical communication activities among Intensive Care Unit (ICU) clinical teams
      with a primary focus on the attending physician. In this paper, we present the
      first ICU communication instrument, and, we introduce the use of database
      management system to aid in discovering patterns and associations within our ICU
      communications data repository.

PMID- 22874367
TI  - Semantic enrichment of medical forms - semi-automated coding of ODM-elements via
      web services.
AB  - Semantic interoperability is an unsolved problem which occurs while working with
      medical forms from different information systems or institutions. Standards like
      ODM or CDA assure structural homogenization but in order to compare elements from
      different data models it is necessary to use semantic concepts and codes on an
      item level of those structures. We developed and implemented a web-based tool
      which enables a domain expert to perform semi-automated coding of ODM-files. For
      each item it is possible to inquire web services which result in unique concept
      codes without leaving the context of the document. Although it was not feasible
      to perform a totally automated coding we have implemented a dialog based method
      to perform an efficient coding of all data elements in the context of the whole
      document. The proportion of codable items was comparable to results from previous
      studies.

PMID- 22874368
TI  - Conducting requirements analyses for research using routinely collected health
      data: a model driven approach.
AB  - BACKGROUND: Medical research increasingly requires the linkage of data from
      different sources. Conducting a requirements analysis for a new application is an
      established part of software engineering, but rarely reported in the biomedical
      literature; and no generic approaches have been published as to how to link
      heterogeneous health data. METHODS: Literature review, followed by a consensus
      process to define how requirements for research, using, multiple data sources
      might be modeled. RESULTS: We have developed a requirements analysis: i-ScheDULEs
      - The first components of the modeling process are indexing and create a rich
      picture of the research study. Secondly, we developed a series of reference
      models of progressive complexity: Data flow diagrams (DFD) to define data
      requirements; unified modeling language (UML) use case diagrams to capture study
      specific and governance requirements; and finally, business process models, using
      business process modeling notation (BPMN). DISCUSSION: These requirements and
      their associated models should become part of research study protocols.

PMID- 22874369
TI  - Classification of ischaemic episodes with ST/HR diagrams.
AB  - Coronary artery disease is the developed world's premier cause of mortality and
      the most probable cause of myocardial ischaemia. More advanced diagnostic tests
      aside, in electrocardiogram (ECG) analysis it manifests itself as a ST segment
      deviation, targeted by both exercise ECG and ambulatory ECG. In ambulatory ECG,
      besides ischaemic ST segment deviation episodes there are also non-ischaemic
      heart rate related episodes which aggravate real ischaemia detection. We present
      methods to transform the features developed for the heart rate adjustment of ST
      segment depression in exercise ECG for use in ambulatory ECG. We use annotations
      provided by the Long-Term ST Database to plot the ST/HR diagrams and then
      estimate the overall and maximal slopes of the diagrams in the exercise and
      recovery phase for each ST segment deviation episode. We also estimate the angle
      at the extrema of the ST/HR diagrams. Statistical analysis shows that ischaemic
      ST segment deviation episodes have significantly steeper overall and maximal
      slopes than heart rate related episodes, which indicates the explored features'
      utility for distinguishing between the two types of episodes. This makes the
      proposed features very useful in automated ECG analysis.

PMID- 22874370
TI  - Collaborative development of knowledge-based support systems: a case study.
AB  - We investigate a user-driven collaborative knowledge engineering and interaction
      design process. The outcome is a knowledge-based support application tailored to
      physicians in the local dementia care community. The activity is organized as a
      part of a collaborative effort between different organizations to develop their
      local clinical practice. Six local practitioners used the generic decision
      support prototype system DMSS-R developed for the dementia domain during a period
      and participated in evaluations and re-design. Additional two local domain
      experts and a domain expert external to the local community modeled the content
      and design of DMSS-R by using the modeling system ACKTUS. Obstacles and success
      factors occurring when enabling the end-users to design their own tools are
      detected and interpreted using a proposed framework for improving care through
      the use of clinical guidelines. The results are discussed.

PMID- 22874371
TI  - Integration of data analysis methods in syndromic surveillance systems.
AB  - Syndromic surveillance systems perform real-time analysis of health data to
      enable early identification of potential public health threats, evaluating
      whether distributional parameters have been increased beyond a threshold. This
      paper presents the applied data analysis methods in five non-industrial
      surveillance systems. Four time series and spatial cluster analysis methods were
      found to be implemented: SMART, EWMA, CuSum and WSARE. Combined use both spatial
      and time series methods is found in the presented surveillance applications. Data
      analysis methods for syndromic surveillance are a constantly emerging field,
      while new statistical methods and algorithms are implemented into surveillance
      systems.

PMID- 22874372
TI  - Statistical disclosure limitation of health data based on Pk-anonymity.
AB  - The Act for the Protection of Personal Information in Japan considers as personal
      information any quasi-identifier that may be used to obtain information that
      identifies individuals through comparisons with datasets. Studies using health
      records are not widely conducted because of the concern regarding the safety of
      anonymized health records. To increase the safety of such records, we used the Pk
      anonymity method. In this method, attributes are probabilistically randomized and
      then reconstructions are performed on the basis of statistical information from
      perturbed data. Hence, it is expected to provide more precise statistics and more
      reliably preserve privacy than the traditional "k-anonymity" method. We
      anonymized health records, performed cross tabulation, and assessed the error
      rate using original data. This study shows that the Pk-anonymity method can be
      used to perform safety statistical disclosures with low error rates, even in
      small cases.

PMID- 22874373
TI  - Ultradian rhythms during day and night in normal and COPD subjects.
AB  - The analysis of heart rate variability (HRV) is a powerful tool in the study of
      the autonomic control of the heart. While circadian HRV rhythms have widely been
      characterized by traditional spectral measures, ultradian oscillations are not
      commonly investigated. In this study the identification of HRV ultradian rhythms
      is assigned to a quantitative measure characterizing the fractal-like behavior of
      the time series: the fractal dimension (FD). In order to assess ultradian
      regulation in Chronic Obstructive Pulmonary Disease (COPD) 24-h Holter ECG
      recordings of 52 COPD and 10 normal (healthy) subjects were analyzed. The FD was
      calculated by Higuchi's algorithm both during daytime and nighttime to highlight
      possible wake-sleep states differences. All subjects showed a similar common
      rhythm (0.06mHz) that persists with generally higher amplitude during night-time.
      A further rhythm becomes predominant in normal subjects in the day-to-night
      transition (0.15mHz), probably under the influence of the REM/non-REM ultradian
      sleep cycle. A very large difference between night and day amplitudes of this
      rhythm and of the next one (at about 0.22mHz) characterize the HRV fractal
      dimension of the Normal in respect of COPD. In conclusion, the FD could be used
      as a marker of ultradian cardiac autonomic regulation providing new insights into
      autonomic physiology of normal and COPD patients.

PMID- 22874374
TI  - A literature overview and comparison of driving impairing condition assessment
      approaches by health enabling technologies.
AB  - Due to demographic change, more elderly people have the need to preserve and
      support mobility by car despite age-related functional limitations. Since
      accidents by the elderly are primarily caused by age related limitations, and not
      by careless or irresponsible behavior, it may be beneficial to detect driving
      impairing conditions. The presented review gives an overview of technologies to
      detect driving impairing conditions like drowsiness and stress or excessive
      demand. A comparison of the approaches to detect these conditions suggests that a
      combination of approaches is the most feasible method. However, there are still
      few systems that focus on the elderly.

PMID- 22874375
TI  - CARDIO-i2b2: integrating arrhythmogenic disease data in i2b2.
AB  - The CARDIO-i2b2 project is an initiative to customize the i2b2 bioinformatics
      tool with the aim to integrate clinical and research data in order to support
      translational research in cardiology. In this work we describe the implementation
      and the customization of i2b2 to manage the data of arrhytmogenic disease
      patients collected at the Fondazione Salvatore Maugeri of Pavia in a joint
      project with the NYU Langone Medical Center (New York, USA). The i2b2 clinical
      research chart data warehouse is populated with the data obtained by the research
      database called TRIAD. The research infrastructure is extended by the development
      of new plug-ins for the i2b2 web client application able to properly select and
      export phenotypic data and to perform data analysis.

PMID- 22874376
TI  - Impact of computerized order sets on practitioner performance.
AB  - Order sets have the potential to provide evidence at the point of care and
      improve healthcare practice. In this study we reviewed the literature to assess
      the effect of computerized order sets on practitioner performance. Our search in
      PubMed and Science direct identified 442 studies of which 16 met our inclusion
      criteria. In 15 studies order sets contributed to the improvement of at least one
      performance outcome. The effect of order sets was evaluated on 34 performance
      outcomes, of which 19 were improved and the rest remained unchanged. The results
      provide evidence that the use of order sets can improve health care practice.

PMID- 22874377
TI  - IT as an enabler of sustainable use of data from innovative technical components
      for assisted living.
AB  - The authors see the major potential of systematically processing data from AAL
      technology in higher sustainability, higher technology acceptance, higher
      security, higher robustness, higher flexibility and better integration in
      existing structures and processes. This potential is currently underachieved and
      not yet systematically promoted. The authors have written a position paper on
      potential and necessity of substantial IT research enhancing Ambient Assisted
      Living (AAL) applications. This paper summarizes the most important challenges in
      the fields health care, data protection, operation and user interfaces. Research
      in medical informatics is necessary among others in the fields flexible
      authorization concept, medical information needs, algorithms to evaluate user
      profiles and visualization of aggregated data.

PMID- 22874378
TI  - IT behind a platform for Translational Cancer Research - concept and objectives.
AB  - The German Consortium for Translational Cancer Research (DKTK) and the Rhine-Main
      Translational Cancer Research Network (RM-TCRN) are designed to exploit large
      population cohorts of cancer patients for the purpose of bio-banking, clinical
      trials, and clinical cancer registration. Hence, the success of these platforms
      is heavily dependent on the close interlinking of clinical data from cancer
      patients, information from study registries, and data from bio-banking systems of
      different laboratories and scientific institutions. This article referring to the
      poster discusses the main challenges of the platforms from an information
      technology point of view, legal and data security issues, and outlines an
      integrative IT-concept concerning a decentralized, distributed search approach
      where data management and search is in compliance with existing legislative
      rules.

PMID- 22874379
TI  - Psychological evaluation of 24-hour home nursing care: application of an analytic
      hierarchy process to improve quality of life.
AB  - Twenty-four-hour home nursing care services for patients with severe diseases
      such as amyotrophic lateral sclerosis have been started in Japan. To improve the
      quality of home nursing care as well as the patients quality of life (QOL), we
      undertook a psychological evaluation of the care services. An analytic hierarchy
      process (AHP) was applied to the psychological evaluation. Forty-eight staff
      replied to our questionnaire, of which twenty-nine staff showed a consistency
      index of less than 0.1. In the first hierarchy, the intensities of importance
      were 0.436 for "quality of care", 0.351 for "staff awareness", and 0.213 for
      "economic efficiency". Most staff appeared to feel that the relationships among
      patients, their families, and staffs were the most important criteria. While many
      staff might have increased their "physical profit" and "burden", the intensities
      of importance for those criteria were low.

PMID- 22874380
TI  - A clinical research analytics toolkit for cohort study.
AB  - This paper presents a clinical informatics toolkit that can assist physicians to
      conduct cohort studies effectively and efficiently. The toolkit has three key
      features: 1) support of procedures defined in epidemiology, 2) recommendation of
      statistical methods in data analysis, and 3) automatic generation of research
      reports. On one hand, our system can help physicians control research quality by
      leveraging the integrated knowledge of epidemiology and medical statistics; on
      the other hand, it can improve productivity by reducing the complexities for
      physicians during their cohort studies.

PMID- 22874381
TI  - An encapsulated R application for the guided analysis of genomic data.
AB  - Microarrays are widely used in biomedical research. However, researchers
      conducting the biomedical assays are often not skilled to perform the necessary
      biostatistical preprocessing of the resulting data. As a result, researchers with
      different backgrounds contribute to the analysis, but often without documenting
      how the data were transformed. For a biomedical research network on liver cancer,
      we implemented a prototype that has two major aims: First, it should guide
      biomedical researchers through the analysis of microarray data by providing a
      limited amount of appropriate choices for the biostatistical procedures to be
      applied. Second, it should help to ensure data quality by documenting all
      transformations applied to the data set.

PMID- 22874382
TI  - First experiences in implementing a software-based support for patient
      recruitment at Heidelberg university hospital.
AB  - Clinical trials have often got problems in achieving their recruitment target.
      Making the recruitment process more efficient and timely is tried to achieve in
      Heidelberg by implementing a software-based system to support patient
      recruitment. The architecture implemented in Heidelberg was developed in a multi
      center research project named 'EHR-based support for patient recruitment'. The
      architecture is generic as five distinct university hospitals developed it and
      found it implementable. The same architecture is also implemented at four other
      university hospitals in Germany. The system was implemented into the existing
      system architecture and can thus be implemented by the vendor of the system. This
      makes the system available to all customers of named systems.

PMID- 22874383
TI  - Medical students and e-Health.
AB  - The term eHealth is widely used in both scientific literature and in everyday
      life. There are many activities related to eHealth both globally and in Europe.
      In Croatia, eHealth is a priority area of the eCroatia programme. There is no
      doubt that eHealth is the environment where present and prospective medical
      students will work after leaving medical schools. In order to find out what
      medical students think eHealth is and which information about eHealth reach them,
      we started this project with second year medical students in academic year
      2010/2011. At the very beginning of medical informatics course, students were
      asked to write an essay with the title "eHealth" based on their existing
      knowledge and experiences on this topic. Till now 147 written contributions were
      analyzed. We performed lexicometric analysis and correspondence analysis using
      French software Dtm-Vic for textual analysis. Very modest vocabulary and choice
      of words imply that students have little personal experience and knowledge about
      eHealth. Students who had medical secondary school education described eHealth
      differently, probably because they encounter some of eHealth applications while
      attending lectures in health care institutions.

PMID- 22874384
TI  - Multiple disciplines synergy tools for Ph.D. Students of biomedical informatics
      at Charles University in Prague.
AB  - The poster describes doctoral degree studies in biomedical informatics at Charles
      University in Prague. Particularly important in educational programmes and
      knowledge dissemination is the role of Internet. Therefore we also describe
      special activities concerned with the specific research at the First Faculty of
      Medicine of Charles University in Prague. These are selected tools for blended
      learning tools, ExaMe system and the role of the European Journal for Biomedical
      Informatics (EJBI), an official multilingual journal of EFMI, for Ph.D. student's
      cooperation and understanding the multidisciplinary field of biomedical
      informatics [1].

PMID- 22874385
TI  - Translational meta-analysis tool for temporal gene expression profiles.
AB  - Widespread use of microarray technology that led to highly complex datasets often
      is addressing similar or related biological questions. In translational medicine
      research is often based on measurements that have been obtained at different
      points in time. However, the researcher looks at them as a progression over time.
      If a biological stimulus shows an effect on a particular gene that is reversed
      over time, this would show, for instance, as a peak in the gene's temporal
      expression profile. Our program SPOT helps researchers find these patterns in
      large sets of microarray data. We created the software tool using open-source
      platforms and the Semantic Web tool Protege-OWL.

PMID- 22874386
TI  - Pluripotent stem cells in mice.
AB  - Pluripotent stem cells are able to self-renew and to differentiate into all adult
      cell types. Many studies report data describing these cells and characterize them
      in molecular terms. Gene expression data of pluripotent and non-pluripotent cells
      from mouse were assembled. Machine learning was applied to classify samples into
      pluripotent and non-pluripotent cells. To identify minimal sets of best
      biomarkers, three methods were used: information gain, random forests, and
      genetic algorithm.

PMID- 22874387
TI  - Introducing a composite index of information quality for medical web sites.
AB  - In this paper we present the MIR index, a composite index of Medical Information
      Reliability. This percentage index is intended as a simple indicator of
      Information Quality of medical online resources from the perspective of their
      potential consumers. We exemplify its application in the domain of the Non
      Conventional and Complementary Medicine (NCM/CAM) for its lack of institutional
      professional figures; yet the structure of the index makes it suitable also for
      other healthcare-related domains where guidelines for IQ assurance exist.

PMID- 22874388
TI  - Concise healthcare-associated infection reporting and benchmarking with minimal
      staff resources.
AB  - We report on intelligent information technology tools that produce fully
      automated surveillance reports of high precision for 12 intensive care units
      (ICUs) without relevant time expenditure of infection control or ICU staff. This
      is accomplished by MONI-ICU, a computerized system for automated identification
      and continuous monitoring of ICU-associated infections, which makes surveillance
      data readily accessible and presents them in easily perceptible reporting format.

PMID- 22874389
TI  - Developing an eLearning tool formalizing in YAWL the guidelines used in a
      transfusion medicine service.
AB  - The blood transfusion is a complex activity subject to a high risk of eventually
      fatal errors. The development and application of computer-based systems could
      help reducing the error rate, playing a fundamental role in the improvement of
      the quality of care. This poster presents an under development eLearning tool
      formalizing the guidelines of the transfusion process. This system, implemented
      in YAWL (Yet Another Workflow Language), will be used to train the personnel in
      order to improve the efficiency of care and to reduce errors.

PMID- 22874390
TI  - E-learning for neurological bladder management.
AB  - Regarding the impact of visceral dysfunction on quality of life, bowel and
      bladder management is a very important problem. The management of the patient
      with neurological bladder is often a source of uncertainty for both patients and
      healthcare personnel. Since the need of specialized training is growing, two CME
      e-learning courses have been developed to provide physicians and nurses
      competencies for the enhancement of the daily life of the patients. The present
      study aims at evaluating courses attendance and outcomes. Attendance data confirm
      the interest for both courses. The results document a pretty good objective and
      subjective effectiveness of the e-learning courses but low attitude to exploit he
      support of an asynchronous tutor. The analysis of test results gives some hints
      for eventual quality improvement of the courses themselves.

PMID- 22874391
TI  - Patient empowerment in the process of sickness certificates.
AB  - A national patient portal for secure communication between the patients/citizens
      and primary care (Mina vardkontakter) is available in Sweden. This system was
      used in a pilot project in the Stockholm County where patients were invited to
      prepare the visit to their physician for the discussion on the need for prolonged
      sickness leave by filling out a web based questionnaire on their current health
      status and working conditions. The opinions of the patients and their primary
      care physicians about the system were analyzed with positive feedback.

PMID- 22874392
TI  - Patient satisfaction in a context-aware hospital guidance system.
AB  - This paper presents the design of a system for a context-aware guidance service
      for hospital outpatients. Many patients have difficulties in knowing what to do
      and where to go due to the complexity of hospital-related processes and building
      structures. The intelligent hospital of the future will evolve in a smart way to
      automatically provide patients' smart mobile devices with relevant guidance
      information regarding their tasks, location, and process. In this study, we
      developed a context-aware-based hospital digital guidance system and evaluated
      ser satisfaction with respect to outpatient visits. From our pilot experiments
      with 15 outpatients, they were satisfied with the service. We believe that such a
      smart system would be a promising model for developing the intelligent hospitals
      of the future.

PMID- 22874393
TI  - A special query tool in the hospital information system to recognize patients and
      to increase patient numbers for clinical trials.
AB  - A powerful hospital information system (HIS) contains information about
      diagnostic and disease data of all patients in a hospital. In the university
      hospital in Frankfurt / Main Germany more than 80% of all wards are completely
      "paperless". But the identification of patients for clinical trials is very
      difficult. We developed a special query and reporting tool in the HIS to
      recognize patients with a specific disease and with basic inclusion and exclusion
      criteria for a specific clinical trial. With the help of this query tool it is
      possible to increase significantly the patient numbers for clinical trials in a
      short period.

PMID- 22874394
TI  - Design of a computerized provider order entry system for ordering of
      chemotherapy.
AB  - With the developments in medical information systems and the widespread
      establishment of medical information systems that include computerized order
      communication systems (OCSs), there has been an increase in the establishment of
      computerized chemotherapy order systems. In this study, we aim to design an
      improved computerized provider order entry (CPOE) system that integrates a
      chemotherapy ordering system that can issue a customized order in response to a
      provider's diverse chemotherapy prescription needs with an automated issuance of
      dosage, treatment schedule, and treatment method. We expect the newly designed
      system to be able to prevent the common errors in complex chemotherapy ordering
      systems and reduce the time required for ordering.

PMID- 22874395
TI  - Development and evaluation of an expert system for the diagnosis of child autism.
AB  - This paper presents the development of an expert system for the diagnosis of
      child autism and discusses potential benefits of its implementation in a clinical
      environment. The development of the expert system was based on a diagnostic
      algorithm supported by a developmental scale (PEDS) and a diagnostic tool of
      autism (CARS). Twelve nurses who work in pediatric hospital were asked to use the
      expert system for a session of 30 minutes and were asked to assess its
      usefulness, usability and diagnostic value. The majority of nurses agree that it
      is a useful and promising diagnostic tool for the clinical practice and for the
      identification of potential child autism cases.

PMID- 22874396
TI  - ICF machine: a web-based system for collection of ICF data.
AB  - The International Classification of Functioning, Disability and Health (ICF) is a
      WHO classification for health and health-related issues. In order to foster ICF
      application in information systems, we devised an implementation profile in ClaML
      (Classification Markup Language) that allows for representation of ICF subsets
      and we developed a web-based system for collecting ICF data based on from their
      ClaML representation. The implementation profile and the application have been
      tested on 17 subsets, which have been translated into ClaML and then submitted to
      the web application, to produce test documents.

PMID- 22874397
TI  - 'Onco alerts' to support acute oncology services.
AB  - The National Chemotherapy Advisory Group report has recommended that all
      hospitals in the UK with an Emergency Department should establish an acute
      oncology (AO) service. Acute oncology, when implemented at a clinical network
      level, presents significant challenges for informatics, including the requirement
      for 'onco alerts' - automated notification of admission of potential cancer
      patients, whose diagnosis may not be recorded on the admitting hospital's IT
      systems. In this short paper we present a case study and describe an approach to
      supporting the development of AO services with cross-organisational information
      systems.

PMID- 22874398
TI  - Promoting generic medication prescribing by order interface redesign: small
      change, large impact.
AB  - Prescription drugs are a significant component of the ever increasing health care
      costs. We describe the effects on generic medication prescribing behavior
      achieved through redesign of the order entry interface of our institutions
      ambulatory electronic health record. The redesign involved custom programming
      that automatically substituted brand medications with their generic equivalents
      and only allowed continuation with the brand medication if the clinician made an
      extra mouse click selecting "dispense as written". We conducted a before-after
      retrospective study around the time of the redesign and witnessed a net 36.9%
      percentage increase in the number of generic medications prescribed.

PMID- 22874399
TI  - Study of Iranian breast cancer registration via established online system during
      2011.
AB  - The present paper reports the results of a project aimed at providing Iran with a
      an online registry for breast cancer patients. A new ad hoc system/software has
      been developed in order to collect patients' data from the first visit to follow
      up visits, including tests and Herceptin based therapy. The system has been
      designed to address both healthcare personnel needs, but also decision makers'
      information needs. After having identified in the country the laboratories
      performing the specific tests and the pharmacies that distribute Hercepting, the
      developed software have been installed in order to build the operational network
      representing the input points for the register. In 8 months of usage the results
      are: * Total number of Patients: 2240 inhabitant * Total number of doctors have
      participated in the program: 229 persons * Number of provinces contributing to
      the project: 17 provinces out of 30.  Online registry of breast cancer is
      country's requirement because this system not only delivers services for
      laboratories, pharmacies and all physicians for their patients' follow up and
      monitoring, but also provides ability to access and analyze collected data for
      managers and experts.

PMID- 22874400
TI  - Clinical decision support for monitoring drug-drug-interactions and potassium
      increasing drug combinations: need for specific alerts.
AB  - Computer-triggered reminders alerting physicians on every potentially harmful
      drug-drug-interaction (DDI) induce alert fatigue due to frequent messages of
      limited clinical relevance. On demand DDI-checks, however, are not commonly used
      by physicians. Optimal strategies for sustained quality assurance have to
      consider patients' risk factors and focus on the most significant DDIs only. An
      approach is proposed based on the analysis of concurrent prescription of
      potassium-sparing diuretics and potassium supplements (CPPP), which are the most
      frequent DDIs classified as contraindicated. Although the frequency of monitoring
      potassium serum levels declined during prolonged periods of CPPP, the likelihood
      of observing a hyperkalaemia increased. The median treatment period of CPPP was
      3.3 days, whereas hyperkalaemia occurred after a median observation time of 4.5
      days of CPPP. Thus, computer-triggered reminders for ordering potassium serum
      levels may be indicated if monitoring has been discontinued after 48h of CPPP.

PMID- 22874401
TI  - Decision support system based semantic web for personalized patient care.
AB  - Personalized medicine may be considered an extension of traditional approaches to
      understanding and treating diseases, but with greater precision. A profile of a
      patient's genetic variation can guide the selection of drugs or treatment
      protocols that minimize harmful side effects or ensure a more successful outcome.
      In this paper we describe a decision support system designed to assist physicians
      for personalized care, and methodology for integration in the clinical workflow.
      A reasoning method for interacting heterogeneous knowledge and data is a
      necessity in the context of personalized medicine. Development of clinical
      decision support based semantic web for personalized patient care is to achieve
      its potential and improve the quality, safety and efficiency of healthcare.

PMID- 22874402
TI  - Development of an electronic nursing records system based on information models
      and clinical practice guidelines.
AB  - The purpose of this study was to test the feasibility of an electronic nursing
      records system for perinatal care that is based on information models and
      clinical practice guidelines in perinatal care. We first generated 799 nursing
      statements describing nursing assessment, diagnoses, interventions, and outcomes
      using the entities, attributes, and value sets of detailed clinical models for
      perinatal care that we developed in a previous study. We then extracted 506
      detailed recommendations from clinical practice guidelines. Finally, we created
      sets of nursing statements to be used for nursing documentation by grouping
      nursing statements based on these detailed recommendations. A prototype
      electronic nursing records system providing nurses with detailed recommendations
      for nursing practice and sets of nursing statements based on the detailed
      recommendations to guide nursing documentation was developed and evaluated.

PMID- 22874403
TI  - Formative usability evaluation of a web-based insulin self-titration system:
      preliminary results.
AB  - We developed a web-based system supporting patients in insulin self-titration and
      their caregivers in monitoring patients' self-management activities. Since
      usability flaws could cause user attrition and compromise patient safety, we
      evaluated the system's usability prior to its implementation in practice. Two
      pairs of researchers conducted cognitive walkthrough sessions and identified 81
      unique usability problems, including four with a potential impact on patient
      safety. Usability evaluations could reveal many usability problems and allow
      solving the problems while avoiding user attrition and potential adverse patient
      events.

PMID- 22874404
TI  - MInD: moving in the dark.
AB  - Visually-impaired people can develop several unhealthy behaviors, including the
      lack of physical activity or sports, due to the incomplete maturity in the
      control of their body in the space. This research focuses on the creation of an
      "exergame" - a videogame especially designed to stimulate physical exercise -
      that, through voice commands, allows the visually impaired users to practice
      physical activity and train their abilities. This tool has been developed
      starting from an existing dance-game, by generating some appropriate interfaces
      that also involve the sensory channel of sight. Our research aims to study the
      effects related to this exergame on the motor control mechanism in a blind
      children's group, aged between 8 and 13 years: it focuses also on the joint use
      of movement analysis systems and of videogames in order to stimulate the physical
      activity in these subjects.

PMID- 22874405
TI  - An example of a multi-professional process-oriented structured documentation
      bound to SNOMED CT.
AB  - Structured code-based documentation, i.e. templates which restrain the user with
      predetermined terms/phrases bound to terminologies, offers opportunities for
      advanced types of retrieval and guides the user in multiple ways; to act in
      accordance with evidence, for decision support and to achieve adequate
      documentation for the condition in question. This type of documentation is
      especially appropriate in health care processes which are nearly the same every
      time. A template for documentation of the family planning process (abortion) was
      elaborated at a Swedish hospital. It uses both structured elements and free-text
      and covers all information needed in the process. The predetermined terms and
      phrases were bound to SNOMED CT concepts. After the template has been completed,
      it forms the basis for a customary free-text note in the record. The structured
      information is also stored in its original form and can be used for different
      kinds of advanced data retrieval. The documentation is completed during the visit
      and there is no need for additional secretarial work. The implementation has
      reduced the total time used for documentation, reporting and follow up and shows
      that process-oriented structured documentation bound to SNOMED CT improves the
      documentation, supports advanced retrieval of data and reduces resource
      utilization.

PMID- 22874406
TI  - Clinicians' experiences with videoconferencing in psychiatry.
AB  - Videoconferencing may help reduce traveling and may save time and money for
      patients and the health care system. Despite the fact that studies have found
      videoconferencing as good as face-to-face interactions for certain therapies, few
      in northern Norway use this tool routinely for the assessment and treatment of
      patients. We examined clinicians' experiences with videoconferencing and their
      attitudes to using this tool for psychiatric consultations, and discussed the
      findings in light of the Technology Acceptance Model. Obstacles to use and how
      they may be overcome are discussed.

PMID- 22874407
TI  - Development and management of public health education system against emerging
      infectious diseases.
AB  - With recent spread of infectious diseases, worldwide emergency strategies against
      them have been made. As one of such efforts we planned to develop an educational
      program for public health manpower using IT, and produced 4 to 8 minute-long
      flash animations of the following subjects selected by Education Training Expert
      Committee: Self-care guideline on H1N1; Instruction for medical hospital;
      Prevention of hospital acquired infections; Method of sampling & transporting.
      Demonstrative education using an online education system was conducted targeting
      10 doctors working in a rural health center to evaluate the developed animations.
      They received good marks in the factors of credibility and accuracy, but needed
      to improve in that of interaction with educatees. Our suggestion is that we use
      the result of our study as a prototype of education contents on infectious
      diseases, and modify its contents accordingly when a specific disease breaks out.

PMID- 22874408
TI  - Pharmaceutical validation of medication orders using an OWL Ontology and Business
      Rules.
AB  - In this paper we present an application of pharmaceutical validation of
      medication based on an OWL ontology and business rules or more specifically
      clinical decision rules. This application has been developed based on a prototype
      that enables business users to author, execute and manage their Business Rules
      over OWL Ontology. This prototype is based on the Business Rule Management System
      (BRMS) IBM WebSphere ILOG JRules.

PMID- 22874409
TI  - A way to motivate Danish GPs to implement a new national service.
AB  - The Common Medicine card (CMC) is a new national service in Denmark which aim is
      to ensure better patient care and minimize medication errors. All health
      professionals as well as authorities have to use this system. CMC requires
      changing the organization of work for both physicians and clinical staff in
      General Practice (GP). Commissioning of CMC in GP requires a significant effort
      beyond the technical installation of the solution. Finding the right way to
      implement a new service in a busy GP has been the main focus of the national
      project organization MedCom. MedCom has in collaboration with the five regions in
      Denmark, established a joint plan and has created an implementation model
      contraining various initiatives including "after hours" meetings for each service
      provider of EMR (Electronic Medicine Records) in order to disseminate and support
      the new CMC service. This paper shows the status of the "after hours" meetings
      effect in dissemination of CMC from August to November 2011.

PMID- 22874410
TI  - Trend analysis and future development of Taiwan electronic medical records.
AB  - The aim of this study was to validate a specially designed electronic medical
      records (EMRs) questionnaire for use in Taiwan. Published reviews of national
      trends and EMRs characteristics from seven countries in the Americas, Oceania,
      Europe, and Asia were used to design the Google-based document. This
      questionnaire is intended for use by medical institutions, government health
      units, manufacturers, academic institutions, and the public, and may be
      administered by information officers, non-IT staff (physicians, nurses,
      policymakers, vendors), and even people. A modified Delphi method was employed to
      determine the most appropriate content for the questionnaire. In conclusion, this
      research demonstrated trend analysis of several national EMRs, and also
      identified the meaningful use of EMR and establishing governmental EMR office are
      the important directions for Taiwan EMRs.

PMID- 22874414
TI  - A second extracellular site is required for norepinephrine transport by the human
      norepinephrine transporter.
AB  - The human norepinephrine transporter (NET) is implicated in many neurological
      disorders and is a target of tricyclic antidepressants and nisoxetine (NX). We
      used molecular docking simulations to guide the identification of residues likely
      to affect substrate transport and ligand interactions at NET. Mutations to
      alanine identified a hydrophobic pocket in the extracellular cavity of NET,
      comprising residues Thr80, Phe317, and Tyr317, which was critical for efficient
      norepinephrine (NE) transport. This secondary NE substrate site (NESS-2)
      overlapped the NX binding site, comprising Tyr84, Phe317, and Tyr317, and was
      positioned ~11 A extracellular to the primary site for NE (NESS-1). Thr80 in NESS
      2 appeared to be critical in positioning NE for efficient translocation to NESS
      1. Three residues identified as being involved in gating the reverse transport of
      NE (Arg81, Gln314, and Asp473) did not affect NE affinity for NESS-1. Mutating
      residues adjacent to NESS-2 abolished NET expression (D75A and L76A) or appeared
      to affect NET folding (S419A), suggesting important roles in stabilizing NET
      structure, whereas W308A and F388A at the top of NESS-2 abolished both NE
      transport and NX binding. Our findings are consistent with a multistep model of
      substrate transport by NET, for which a second, shallow extracellular NE
      substrate site (NESS-2) is required for efficient NE transport by NET.

PMID- 22874415
TI  - Activation of alpha7 nicotinic receptors by orthosteric and allosteric agonists:
      influence on single-channel kinetics and conductance.
AB  - Nicotinic acetylcholine receptors (nAChRs) are oligomeric transmembrane proteins
      in which five subunits coassemble to form a central ion channel pore.
      Conventional agonists, such as acetylcholine (ACh), bind to an orthosteric site,
      located at subunit interfaces in the extracellular domain. More recently, it has
      been demonstrated that nAChRs can also be activated by ligands binding to an
      allosteric transmembrane site. In the case of alpha7 nAChRs, ACh causes rapid
      activation and almost complete desensitization. In contrast, allosteric agonists
      such as 4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c] quin oline-8
      sulfonamide (4BP-TQS) activate alpha7 nAChRs more slowly and cause only low
      levels of apparent desensitization. In the present study, single-channel patch
      clamp recording has been used to investigate differences in the mechanism of
      activation of alpha7 nAChRs by ACh and 4BP-TQS. The most striking difference
      between activation by ACh and 4BP-TQS is in single-channel kinetics. In
      comparison with activation by ACh, single-channel open times and burst lengths
      are substantially longer (~160-800-fold, respectively), and shut times are
      shorter (~8-fold) when activated by 4BP-TQS. In addition, coapplication of ACh
      and 4BP-TQS results in a further increase in single-channel burst lengths. Mean
      burst lengths seen when the two agonists are coapplied (3099 +/- 754 ms) are ~2.5
      fold longer than with 4BP-TQS alone and ~370-fold longer than with ACh alone.
      Intriguingly, the main single-channel conductance of alpha7 nAChRs, was
      significantly larger when activated by 4BP-TQS (100.3 +/- 2.4 pS) than when
      activated by ACh (90.0 +/- 2.7 pS), providing evidence that activation by
      allosteric and orthosteric agonists results in different alpha7 nAChRs open
      channel conformations.

PMID- 22874416
TI  - A celebration of 100 years of vitamin research but time to revitalise the
      science.

PMID- 22874417
TI  - Current world literature.

PMID- 22874419
TI  - Science and decisions: advancing toxicology to advance risk assessment.
AB  - In 2009, the National Research Council (NRC) released the latest in a series of
      advisory reports on human health risk assessment, titled Science and Decisions:
      Advancing Risk Assessment. This wide-ranging report made a number of
      recommendations related to risk assessment practice at the U.S. Environmental
      Protection Agency that could both influence and be influenced by evolving
      toxicological practice. In particular, Science and Decisions emphasized the
      scientific and operational necessity of a new approach for dose-response
      modeling; addressed the recurring challenge of defaults in risk assessment and
      the question of when research results can be used in place of defaults; and
      reinforced the value of cumulative risk assessment, which would require enhanced
      understanding of the joint influence of chemical and nonchemical stressors on
      health outcomes. The objective of this article is to summarize key messages from
      Science and Decisions, both as a stand-alone report and in comparison with
      another recent NRC report, Toxicity Testing in the 21st Century: A Vision and a
      Strategy. Although these reports have many conclusions in common and reinforce
      similar themes, there are important differences that merit careful consideration,
      such as the move away from apical endpoints in Toxicity Testing and the emphasis
      on benefit-cost analyses and related decision tools in Science and Decisions that
      would be strengthened by quantification of apical endpoints. Moving risk
      assessment forward will require toxicologists to wrestle with the implications of
      Science and Decisions from a toxicological perspective.

PMID- 22874420
TI  - Pharmacokinetics and pharmacodynamics of chlorpyrifos and 3,5,6-trichloro-2
      pyridinol in rat saliva after chlorpyrifos administration.
AB  - Sensors have been developed for noninvasive biomonitoring of the organophosphate
      pesticide chlorpyrifos (CPF), and previous studies have suggested consistent
      partitioning of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of CPF, into
      saliva after exposure to TCPy. The objective of this study was to quantitatively
      evaluate in vivo pharmacokinetics and pharmacodynamics of CPF and TCPy in saliva
      after CPF administration. Rats were coadministered CPF (0.5-5mg/kg) and
      pilocarpine (~13 mg/kg) iv. Saliva and blood were collected, and levels of CPF,
      TCPy, and cholinesterase (ChE) activity were quantified. Experimental results
      suggest that CPF is rapidly metabolized after iv administration. Formation of
      TCPy from administered CPF at the low dose (0.5 mg/kg) was slower than from
      higher CPF doses, potentially due to differences in plasma protein binding to
      CPF. CPF was measured in saliva only at the first time point sampled (0-15 min),
      indicating low partitioning and rapid metabolism. After formation, TCPy
      pharmacokinetics were very similar in blood and saliva. Saliva/blood TCPy
      concentration ratios were not affected by TCPy concentration in blood, saliva
      flow rate, or salivary pH and were consistent with previous studies. ChE activity
      in plasma demonstrated a dose-dependent decrease, and ChE activity in saliva was
      extremely variable and demonstrated no dose relationship. A physiologically based
      pharmacokinetic and pharmacodynamic model for CPF was modified and predicted the
      data reasonably well. It is envisioned that a combination of biomonitoring
      compounds like TCPy in saliva coupled with computational modeling will form an
      approach to measure pesticide exposure to susceptible human populations such as
      agricultural workers.

PMID- 22874422
TI  - Characterization of bulbospongiosus muscle reflexes activated by urethral
      distension in male rats.
AB  - The urethrogenital reflex (UGR) is used as a surrogate model of the autonomic and
      somatic nerve and muscle activity that accompanies ejaculation. The UGR is evoked
      by distension of the urethra and activation of penile afferents. The current
      study compares two methods of elevating urethral intraluminal pressure in
      spinalized, anesthetized male Sprague-Dawley rats (n = 60). The first method,
      penile extension UGR, involves extracting the penis from the foreskin, so that
      urethral pressure rises due to a natural anatomical flexure in the penis. The
      second method, penile clamping UGR, involves penile extension UGR with the
      addition of clamping of the glans penis. Groups of animals were prepared that
      either received no additional treatment, surgical shams, or received bilateral
      nerve cuts (4 nerve cut groups): either the pudendal sensory nerve branch (SbPN),
      the pelvic nerves, the hypogastric nerves, or all three nerves. Penile clamping
      UGR was characterized by multiple bursts, monitored by electromyography (EMG) of
      the bulbospongiosus muscle (BSM) accompanied by elevations in urethral pressure.
      The penile clamping UGR activity declined across multiple trials and eventually
      resulted in only a single BSM burst, indicating desensitization. In contrast, the
      penile extension UGR, without penile clamping, evoked only a single BSM EMG burst
      that showed no desensitization. Thus, the UGR is composed of two BSM patterns: an
      initial single burst, termed urethrobulbospongiosus (UBS) reflex and a subsequent
      multiple bursting pattern (termed ejaculation-like response, ELR) that was only
      induced with penile clamping urethral occlusion. Transection of the SbPN
      eliminated the ELR in the penile clamping model, but the single UBS reflex
      remained in both the clamping and extension models. Pelvic nerve (PelN)
      transection increased the threshold for inducing BSM activation with both methods
      of occlusion but actually unmasked an ELR in the penile extension method.
      Hypogastric nerve (HgN) cuts did not significantly alter any parameter.
      Transection of all three nerves eliminated BSM activation completely. In
      conclusion, penile clamping occlusion recruits penile and urethral primary
      afferent fibers that are necessary for an ELR. Urethral distension without
      significant penile afferent activation recruits urethral primary afferent fibers
      carried in either the pelvic or pudendal nerve that are necessary for the single
      burst UBS reflex.

PMID- 22874421
TI  - Adenosine A1-receptor knockout mice have a decreased blood pressure response to
      low-dose ANG II infusion.
AB  - Adenosine, acting on A(1)-receptors (A(1)-AR) in the nephron, increases sodium
      reabsorption, and also increases renal vascular resistance (RVR), via A(1)-ARs in
      the afferent arteriole. ANG II increases blood pressure and RVR, and it
      stimulates adenosine release in the kidney. We tested the hypothesis that ANG II
      infused hypertension is potentiated by A(1)-ARs' influence on Na(+) reabsorption.
      Mean arterial pressure (MAP) was measured by radiotelemetry in A(1)-AR knockout
      mice (KO) and their wild-type (WT) controls, before and during ANG II (400 ng.kg(
      1).min(-1)) infusion. Baseline MAP was not different between groups. ANG II
      increased MAP in both groups, but on day 12, MAP was lower in A(1)-AR KO mice
      (KO: 128 +/- 3 vs. 139 +/- 3 mmHg, P < 0.01). Heart rates were significantly
      different during days 11-14 of ANG II. Basal sodium excretion was not different
      (KO: 0.15 +/- 0.03 vs. WT: 0.13 +/- 0.04 mmol/day, not significant) but was
      higher in KO mice 12 days after ANG II despite a lower MAP (KO: 0.22 +/- 0.03 vs.
      WT: 0.11 +/- 0.02 mmol/day, P < 0.05). Phosphate excretion was also higher in
      A(1)-AR KO mice on day 12. Renal expression of the sodium-dependent phosphate
      transporter and the Na(+)/glucose cotransporter were lower in the KO mice during
      ANG II treatment, but the expression of the sodium hydrogen exchanger isoform 3
      was not different. These results indicate that the increase in blood pressure
      seen in A(1)-AR KO mice is lower than that seen in WT mice but was increased by
      ANG II nonetheless. The presence of A(1)-ARs during a low dose of ANG II-infusion
      limits Na(+) and phosphate excretion. This study suggests that A(1)-AR
      antagonists might be an effective antihypertensive agent during ANG II and volume
      dependent hypertension.

PMID- 22874423
TI  - CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in
      undisturbed rats.
AB  - Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the
      most studied form, we reported that CCK-58 is the only detectable endocrine
      peptide form in rats. We investigated the dark-phase rat chow intake pattern
      following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats
      were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg),
      or vehicle. Food intake pattern was assessed during the dark phase using an
      automated weighing system that allowed continuous undisturbed monitoring of
      physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1
      h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly
      effective (-49% and -44%). CCK-58 increased the latency to the first meal,
      whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8
      nmol/kg, -41%) but not after CCK-58. At this dose, CCK-8 increased the satiety
      ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When
      behavior was assessed manually, CCK-8 reduced locomotor activity (-31%), whereas
      grooming behavior was increased (+59%). CCK-58 affected neither grooming nor
      locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58
      is achieved by differential modulation of food intake microstructure and
      behavior. These data highlight the importance of studying the molecular forms of
      peptides that exist in vivo in tissue and circulation of the animal being
      studied.

PMID- 22874424
TI  - Enhanced renal Na+ reabsorption by carbohydrate in beverages during restitution
      from thermal and exercise-induced dehydration in men.
AB  - We examined whether carbohydrate in beverages accelerated fluid retention during
      recovery from thermal and exercise-induced dehydration and whether it was caused
      in part by an enhanced renal Na+ reabsorption rate due to insulin secretion.
      After dehydrating by ~2.3% body weight by exercise in a hot environment, seven
      young men underwent high-carbohydrate, low-carbohydrate, or control rehydration
      trials by drinking one of three beverages with 3.4 g glucose + 3.1 g fructose,
      1.7 g glucose + 1.6 g fructose, or 0.0 g glucose + 0.0 g fructose per deciliter,
      respectively, in a common composition of electrolyte solution: 21 meq/l [Na+], 5
      meq/l [K+], 16.5 meq/l [Cl-], 10 meq/l [citrate(-3)]. They drank the same amount
      of beverage as total body weight loss within 30 min. During the 60 min before the
      start of drinking and the following 180 min, we measured plasma volume (PV),
      plasma glucose ([Glc]p), serum insulin ([Ins]s), plasma Na+ concentrations, and
      the renal clearances of inulin, lithium, and Na+ with plasma vasopressin ([AVP]p)
      and aldosterone concentrations ([Ald]p) every 30 min. After dehydration, PV
      decreased by ~5% and plasma osmolality increased by ~6 mosmol/kg H2O in all
      trials with no significant differences among them. We found in the high
      carbohydrate trial that 1) PV increased faster than in the control trial and
      remained at the higher level than other trials for the last 60 min (P < 0.05); 2)
      accumulated urine volume was smallest after 90 min (P < 0.05); 3) the renal Na+
      reabsorption rate was greatest for the first 120 min (P < 0.05); 4) during which
      period [AVP]p and [Ald](p) were not significantly different from other trials
      (both, P > 0.9); and 5) [Glc](p) and [Ins]s were highest from 45 to 105 min (P <
      0.05) during rehydration. Thus carbohydrate in beverages enhances renal Na+
      reabsorption, and insulin is possibly involved in this enhancement.

PMID- 22874425
TI  - Excess protein O-GlcNAcylation and the progression of diabetic cardiomyopathy.
AB  - We examined the role that enzymatic protein O-GlcNAcylation plays in the
      development of diabetic cardiomyopathy in a mouse model of Type 2 diabetes
      mellitus (DM2). Mice injected with low-dose streptozotocin and fed a high-fat
      diet developed mild hyperglycemia and obesity consistent with DM2. Studies were
      performed from 1 to 6 mo after initiating the DM2 protocol. After 1 mo, DM2 mice
      showed increased body weight, impaired fasting blood glucose, and
      hyperinsulinemia. Echocardiographic evaluation revealed left ventricular
      diastolic dysfunction by 2 mo and O-GlcNAcylation of several cardiac proteins and
      of nuclear transcription factor Sp1. By 4 mo, systolic dysfunction was observed
      and sarcoplasmic reticulum Ca(2+) ATPase expression decreased by 50%. Fibrosis
      was not observed at any timepoint in DM2 mice. Levels of the rate-limiting enzyme
      of the hexosamine biosynthetic pathway, glutamine:fructose-6-phosphate
      amidotransferase (GFAT) were increased as early as 2 mo. Fatty acids, which are
      elevated in DM2 mice, can possibly be linked to excessive protein O-GlcNAcylation
      levels, as cultured cardiac myocytes in normal glucose treated with oleic acid
      showed increased O-GlcNAcylation and GFAT levels. These data indicate that the
      early onset of diastolic dysfunction followed by the loss of systolic function,
      in the absence of cardiac hypertrophy or fibrosis, is associated with increased
      cardiac protein O-GlcNAcylation and increased O-GlcNAcylation levels of key
      calcium-handling proteins. A link between excessive protein O-GlcNAcylation and
      cardiac dysfunction is further supported by results showing that reducing O
      GlcNAcylation by O-GlcNAcase overexpression improved cardiac function in the
      diabetic mouse. In addition, fatty acids play a role in stimulating excess O
      GlcNAcylation. The nature and time course of changes observed in cardiac function
      suggest that protein O-GlcNAcylation plays a mechanistic role in the triggering
      of diabetic cardiomyopathy in DM2.

PMID- 22874427
TI  - Catestatin has an unexpected effect on the intrathecal actions of PACAP
      dramatically reducing blood pressure.
AB  - This study focuses on presympathetic neurons of the rostral ventrolateral medulla
      (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are
      colocalized in RVLM neurons and are released under specific conditions to
      modulate efferent homeostatic responses. Of particular interest here are two
      peptides colocalized in catecholaminergic RVLM neurons: catestatin and pituitary
      adenylate cyclase-activating polypeptide (PACAP). Chromogranin A-derived
      catestatin is a potent endogenous noncompetitive nicotinic and adrenoreceptor
      antagonist. Catestatin impairs adenylate cyclase and phospholipase C action:
      mechanisms engaged by PACAP. Although PACAP and catestatin are likely coreleased,
      the possible effects of this are unknown. We aimed to determine whether
      catestatin affects the normal sympathoexcitatory but isotensive responses to
      intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley
      rats (n = 22) were given an intrathecal injection of catestatin at different
      times prior to intrathecal administration of PACAP-38. Arterial pressure,
      splanchnic sympathetic nerve activity, heart rate, and reflex responses to
      baroreceptor and chemoreceptor activation were recorded. The key findings of this
      study are that pretreatment with catestatin time dependently enhances the PACAP
      38 effect on mean arterial pressure and enhances sympathetic barosensitivity and
      chemosensitivity. The time-scale of the effect of catestatin on the response to
      PACAP-38 strongly suggests that catestatin is either causing changes in gene
      expression to exert its effects, or modifying intracellular mechanisms normally
      engaged by PAC(1) receptors. The ability of catestatin pretreatment to enhance
      barosensitivity and chemosensitivity after PACAP-38 injection supports the
      hypothesis that catestatin manipulates the intracellular environment within
      sympathetic neurons in a way that increases responses to PACAP.

PMID- 22874426
TI  - Intrinsic properties of the sodium sensor neurons in the rat median preoptic
      nucleus.
AB  - The essential role of the median preoptic nucleus (MnPO) in the integration of
      chemosensory information associated with the hydromineral state of the rat relies
      on the presence of a unique population of sodium (Na+) sensor neurons. Little is
      known about the intrinsic properties of these neurons; therefore, we used whole
      cell recordings in acute brain slices to determine the electrical fingerprints of
      this specific neural population of rat MnPO. The data collected from a large
      sample of neurons (115) indicated that the Na+ sensor neurons represent a
      majority of the MnPO neurons in situ (83%). These neurons displayed great
      diversity in both firing patterns induced by transient depolarizing current steps
      and rectifying properties activated by hyperpolarizing current steps. This
      diversity of electrical properties was also present in non-Na+ sensor neurons.
      Subpopulations of Na+ sensor neurons could be distinguished, however, from the
      non-Na+ sensor neurons. The firing frequency was higher in Na+ sensor neurons,
      showing irregular spike discharges, and the amplitude of the time-dependent
      rectification was weaker in the Na+ sensor neurons than in non-Na+ sensor
      neurons. The diversity among the electrical properties of the MnPO neurons
      contrasts with the relative function homogeneity (Na+ sensing). However, this
      diversity might be correlated with a variety of direct synaptic connections
      linking the MnPO to different brain areas involved in various aspects of the
      restoration and conservation of the body fluid homeostasis.

PMID- 22874428
TI  - Tubular esophageal duplication: further evidence of a possible endoscopic
      treatment.

PMID- 22874429
TI  - Assessment of the daily intake of 62 polychlorinated biphenyls from dietary
      exposure in South Korea.
AB  - The dietary intake of polychlorinated biphenyls (PCBs) was estimated using the
      sum of 62 PCB congeners (?(62)PCBs), including seven indicator PCBs and 12 dioxin
      like PCBs, in the South Korea. In this study, 200 individual food samples
      belonging to 40 different foodstuffs were investigated to estimate the
      distribution of PCB congeners in five sampling cities. PCB exposure was estimated
      using Korean dietary habits as established by the National Health and Nutrition
      Examination Survey (NHANES). The PCB concentrations in rice, the most frequently
      consumed food in Korea, was relatively low in whole food samples. The mean PCB
      levels measured in fish were the highest in this study, but each fish is consumed
      in relatively small amounts by the general population. Therefore, the daily
      dietary intake should also be considered with regard to human exposure to PCBs,
      especially with the consumption of contaminated foods. Dioxin-like PCB levels
      were also calculated using TEF values that were established in 2005. The average
      levels (pg TEQ/g) were 0.0002 for rice and 0.0098 for fish. The dioxin-like PCBs
      accounted for a relatively small percentage of the total PCBs, compared to
      previous studies. According to our research, the health risks associated with
      exposure to PCBs could be estimated using the tolerable daily intake (TDI) of the
      general population.

PMID- 22874430
TI  - Heterotaxy and isomerism.

PMID- 22874431
TI  - Quality of life from the perspective of the palliative care patient in a resource
      poor community in South Africa.
AB  - OBJECTIVE: Quality of life is an ill-defined term, as it means different things
      to different people. Quality of life has been well researched, especially with
      respect to people with cancer, but not necessarily from the perspective of the
      patient, and also, not in Third World, resource-poor countries. The objective of
      this study was to explore quality of life from the perspective of palliative care
      patients managed at a palliative care clinic serving a resource-poor community in
      Tshwane, South Africa. METHOD: An exploratory, qualitative phenomenological study
      was conducted. The target population for this study was all patients managed at a
      palliative care clinic serving a resource-poor community in Tshwane. Self-report
      data were gathered by means of in-depth interviews. The data were analyzed using
      a template analysis style as well as content analysis using open coding. Data
      analysis was done concurrently with data gathering. Data saturation was reached
      after 10 interviews (n = 10). RESULTS: Three themes arose from the data: factors
      that had a positive influence on quality of life, factors that had a negative
      influence on quality of life, and experience of quality of life. Work played the
      most important role in quality of life whereas only one participant linked
      symptom control with quality of life. Experiencing symptoms, rejection, and
      stigmatization had a negative influence on quality of life. Friends and religion
      played a significant role and added to quality of life. SIGNIFICANCE OF RESULTS:
      Life was a daily struggle for survival. Poverty was so overwhelming that quality
      of life was primarily measured in terms of the ability to buy food and other
      basic commodities.

PMID- 22874432
TI  - Progesterone and estradiol in cat placenta--biosynthesis and tissue
      concentration.
AB  - Ovarian and placental steroids are essential for the maintenance of pregnancy. In
      some mammals it is evident that the placenta is responsible for the production of
      steroids. However, in the domestic cat, steroid secretion from the placenta has
      not yet been elucidated. Our study aimed to find out whether feline placentae are
      able to produce steroids. Placentae from different pregnancy stages were analyzed
      for mRNA expression of five steroidogenic enzymes (HSD3B1, CYP11A1, CYP17A1,
      HSD17B1 and CYP19A1) and for tissue concentrations of progesterone and estradiol.
      Steroidogenic enzymes responsible for the final steps of estradiol (CYP19A1) and
      progesterone synthesis (HSD3B) were expressed at very high levels and followed
      almost the same pattern over pregnancy as the intraplacental hormones themselves.
      By contrast, the other enzymes were found in very low quantities suggesting that
      biosynthesis occurs via extra-placental steroid precursors. The plasma steroid
      profiles measured by other groups differ from the placental hormone courses
      determined by us; therefore we conclude that the feline placenta can produce
      progesterone and estradiol.

PMID- 22874433
TI  - Protein thiol oxidation and formation of S-glutathionylated cyclophilin A in
      cells exposed to chloramines and hypochlorous acid.
AB  - Neutrophil oxidants, including the myeloperoxidase products, HOCl and
      chloramines, have been linked to endothelial dysfunction in inflammatory diseases
      such as atherosclerosis. As they react preferentially with sulfur centers, thiol
      proteins are likely to be cellular targets. Our objectives were to establish
      whether there is selective protein oxidation in vascular endothelial cells
      treated with HOCl or chloramines, and to identify sensitive proteins. Cells were
      treated with HOCl, glycine chloramine and monochloramine, reversibly oxidized
      cysteines were labeled and separated by 1D or 2D SDS-PAGE, and proteins were
      characterized by mass spectrometry. Selective protein oxidation was observed,
      with chloramines and HOCl causing more changes than H(2)O(2). Cyclophilin A was
      one of the most sensitive targets, particularly with glycine chloramine.
      Cyclophilin A was also oxidized in Jurkat T cells where its identity was
      confirmed using a knockout cell line. The product was a mixed disulfide with
      glutathione, with glutathionylation at Cys-161. Glyceraldehyde-3-phosphate
      dehydrogenase, peroxiredoxins and cofilin were also highly sensitive to
      HOCl/chloramines. Cyclophilins are becoming recognized as redox regulatory
      proteins, and glutathionylation is an important mechanism for redox regulation.
      Cells lacking Cyclophilin A showed more glutathionylation of other proteins than
      wild-type cells, suggesting that cyclophilin-regulated deglutathionylation could
      contribute to redox changes in HOCl/chloramine-exposed cells.

PMID- 22874434
TI  - Characterization of rabbit aldose reductase-like protein with 3beta
      hydroxysteroid dehydrogenase activity.
AB  - In this study, we isolated the cDNA for a rabbit aldose reductase-like protein
      that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10
      and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant
      AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the
      substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In
      contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5alpha/beta
      dihydro-C19/C21/C24-steroids into the corresponding 3beta-hydroxysteroids,
      showing K(m) of 1.3-9.1 MUM and k(cat) of 1.1-7.6 min(-1). The stereospecific
      reduction was also observed in the metabolism of 5alpha- and 5beta
      dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was
      ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with
      3beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may
      function as a 3-ketoreductase, as well as a defense system against cytotoxic
      carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3
      ketoreductase activity were investigated by replacement of Phe303 and Met304 in
      AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations
      (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting
      the two residues play critical roles in recognition of the steroidal substrate.

PMID- 22874435
TI  - Risk factors for unsuccessful peripheral blood stem cell harvesting using
      granulocyte-colony stimulating factor mobilization in patients with multiple
      myeloma.
AB  - The aim of this study was to determine factors that influence unsuccessful
      peripheral blood stem cell (PBSC) harvesting in patients with multiple myeloma
      (MM). Retrospective data of 186 MM patients who received G-CSF as mobilization
      were analyzed. Patients with successful harvest were compared with those who
      failed (using 2 definitions of failure <2 and <4 CD34 cells*10(6)/mm(3)). The
      groups were compared regarding age, gender, body weight, baseline platelet count,
      receipt of radiotherapy, number of prior chemotherapy regimens, PBSC count before
      collection, processed and collected volume, collect replace, number of sessions
      and final number of PBSC collected. By multivariate analysis, a baseline platelet
      count <161,000 cells/mm(3) was associated with PBSC harvest lower than
      2*10(6)/kg, and age >58 years was related to PBSC harvest lower than 4*10(6)/kg
      CD34 cells/kg. Patients with these parameters should not receive mobilization
      protocols with G-CSF alone. Alternative protocols should be tested in this high
      risk harvest failure population.

PMID- 22874436
TI  - Study on preparation of universal plasma in Chinese Han population.
AB  - BACKGROUND: Universal plasma proves its importance in emergency situations where
      it simplifies the logistics by eliminating the need for ABO-match. There are now
      two available products of ABO-universal plasma internationally. Such product is
      not available in China yet. Besides the titers of anti-A and anti-B antibodies
      were different among ethnic populations for the same blood type, the distribution
      of blood types was also different. To improve the current status of plasma usage,
      this study was carried to explore optimal preparation procedures of universal
      plasma from Chinese Han population. METHODS: The optimal plasma ratios of A:B,
      A:AB and B:AB were evaluated by saline agglutination and the optimal ratio of
      A:B:AB was established. Three factors influencing the preparation of universal
      plasma including the proportion of plasma, reaction temperature and time were
      analyzed by an orthogonal design. RESULTS: The optimal plasma ratios between the
      two kinds of plasma were A:B=1:3, B:AB=1:3 and A:AB=1:2, respectively. Orthogonal
      design showed that the preparation of universal plasma in Chinese Han population
      could be carried by pooling plasma with the ratio of A:B:AB=6:2.5:1.5 at 22
      degrees C within 1h. CONCLUSION: We have found an optimal ratio of pooled plasma
      for the preparation of universal plasma from Chinese Han population. Our study
      might provide preliminary evidence that Chinese Han donor plasma could contribute
      to a Uniplas product being Asian populations and world-wide applicable. The
      Uniplas anti A and B titers of (below) 1:2 is even lower than currently accepted.

PMID- 22874438
TI  - Patient safety papers. Editorial.

PMID- 22874437
TI  - The efficacy of erythrocytes isolated from blood stored under blood bank
      conditions.
AB  - BACKGROUND: The RBCs storage lesion is most carefully viewed as the sum of all
      the changes in RBCs occurring during the course of storage and that limit their
      survival. MATERIALS AND METHODS: Erythrocytes were isolated from stored blood at
      regular intervals. Oxidative stress markers were analyzed to determine the
      changes during the storage. RESULTS: Antioxidant enzymes--(SOD and CAT), and SH
      showed insignificant variation whereas hemolysis, MDA and AOPP showed significant
      variations. CONCLUSION: The oxidative stress has not successfully overridden the
      protection offered by the endogenous antioxidant system. Prolonged storage may
      result in the onset of erythrocyte deterioration. This clearly indicates that the
      erythrocytes are capable of attenuating ROS with 2 weeks of storage.

PMID- 22874439
TI  - Partners in patient safety.

PMID- 22874440
TI  - The challenges of making care safer: leadership and system transformation.

PMID- 22874441
TI  - Reporting, learning and the culture of safety.
AB  - Systems that provide healthcare workers with the opportunity ot report hazards,
      hazardous situations errors, close calls and adverse events make it possible for
      an organization that receives such reports tu use these opportunities to learn
      and /or hold people accountable for their actions. When organizational learning
      is the primary goal, reporting should be confidential, voluntary and easy to
      perform and should lead to risk mitigation strategies following appropriate
      analysis; conversely, when the goal is accountability, reporting is more likely
      to be made mandatory. reporting systems do not necessarily equate to safer
      patient care and have been criticized for capturing too many mundane events but
      only a small minority of important events. reporting has been inappropriately
      equated with patients safety activity and mistakenly used for "measuring" system
      safety. However, if properly designed and supported, a reporting system can be an
      important component of an organizational strategy ot foster a safety culture.

PMID- 22874442
TI  - Productive complications: emergent ideas in team communication and patient
      safety.

PMID- 22874443
TI  - From discovery to design: the evolution of human factors in healthcare.

PMID- 22874444
TI  - Redesigning the workplace for 21st century healthcare.

PMID- 22874445
TI  - Healthcare-associated infections: new initiatives and continuing challenges.
AB  - Healthcare-associated infections are a major cause of patient morbidity and
      mortality. Fortunately for patients and the healthcare system, there is
      increasing interest in this field and the growing realization that many of these
      infections are highly preventable. We explore some of the newer and more
      promising strategies for decreasing infections, including the use of practice
      bundles, behavioural change strategies, hand hygiene auditing, public reporting
      of infection rates and antimicrobial stewardship. We also identify several areas
      where improvement is needed, including empowering patients to prevent infections,
      building safer healthcare facilities and accepting the limitations of the
      evidence supporting some infection control interventions.

PMID- 22874446
TI  - Medication reconciliation in the hospital: what, why, where, when, who and how?
AB  - Medication reconciliation arose as the solution to the well-documented patient
      safety problem of unintentionally introducing changes in patients' medication
      regimens due to incomplete or inaccurate medication information at transitions in
      care. Unfortunately, medication reconciliation has often been misperceived as a
      superficial administrative accounting task with a "pre-occupation with completing
      forms," resulting in the implementation of ineffective processes. In this
      article, the authors briefly review the evidence supporting medication
      reconciliation but focus more on key practical questions regarding the elements
      of an effective medication reconciliation process: what it should consist of,
      where and when it should occur, who should carry it out and how hospitals should
      implement it. The authors take the why of medication reconciliation to consist
      not just of the professional obligation to avoid causing harm, but also of a
      rational self-interest on the part of healthcare leaders. The authors argue that,
      rather than wasting time implementing a nominal reconciliation process, we should
      invest time and energy in a more robust and effective strategy, and they address
      specific practical questions that arise in such an effort.

PMID- 22874447
TI  - Perspectives on diagnostic failure and patient safety.

PMID- 22874448
TI  - Surgical safety checklist: improved patient safety through effective teamwork.

PMID- 22874449
TI  - Toward safer transitions: how can we reduce post-discharge adverse events?

PMID- 22874450
TI  - Safety in home care: thinking outside the hospital box.

PMID- 22874451
TI  - Is xerostomia a risk factor for cardiovascular morbidity and mortality in
      maintenance hemodialysis patients?
AB  - Xerostomia resulting mostly from hyposalivation and alkaline salivary pH is a
      frequent but often underappreciated symptom in the diseased population of
      maintenance hemodialysis (HD) patients. We reviewed also other xerostomia
      predisposing factors, its specific dental and oral clinical signs and features,
      as well as plausibly detrimental dialysis-specific pro-atherosclerotic and
      cardiovascular consequences. In view of increasing multidisciplinary importance
      of xerostomia, its general, pharmacological and emerging treatment methods were
      presented. Special attention was paid to the untoward and often neglected pro
      xerostomic effects of multiple common medications and substances; they were
      listed and described in more detail. The combined therapeutic approach of
      dentists and nephrologists may effectively alleviate xerostomia and support
      general health condition of maintenance hemodialysis patients.

PMID- 22874452
TI  - Combination therapy of ifenprodil with piroxicam may be an effective therapeutic
      intervention in cerebral stroke: a hypothesis.
AB  - Owing to the intricate and multifaceted pathology of cerebral stroke, multiple
      drug therapy had long been suggested for effective stroke treatment. Therefore,
      the development of a potential new combination of drug is necessitated which can
      bring about desirable improved neuroprotection targeting different pathways
      against ischemic stroke. In this context, we hypothesize the combination effect
      of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b
      selective NMDAR antagonist in animal model of cerebral ischemia. A few past
      studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil
      administered in singlet against cerebral ischemia in animal model, hence we
      hypothesized that by using Piroxicam and Ifenprodil in combination would provide
      additive neuroprotection than either of the agents used alone. In this article,
      we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil
      as a potent combination which may have a positive therapeutic role in treatment
      of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti
      oxidative characteristics of Piroxicam with Ifenprodil which has been proved to
      have neuroprotective, anticonvulsant and antinociceptive effects and has
      potentials for the treatment of several neuropsychiatric disorders, such as
      Parkinson's disease alcoholism and drug addiction.

PMID- 22874453
TI  - Anticancer system created by acrolein and hydroxyl radical generated in enzymatic
      oxidation of spermine and other biochemical reactions.
AB  - A hypothesis suggesting the existence of a ubiquitous physiological anticancer
      system created by two highly reactive oxidative stress inducers with anticancer
      properties, acrolein and hydroxyl radical, is reported in this communication.
      Both components can originate separately or together in several biochemical
      interactions, among them, the enzymatic oxidation of the polyamine spermine,
      which appear to be their main source. The foundations of this hypothesis
      encompass our initial search for growth-inhibitors or anticancer compounds in
      biological material leading to the isolation of spermine, a polyamine that became
      highly cytotoxic through the generation of acrolein, when enzymatically oxidized.
      Findings complemented with pertinent literature data by other workers and
      observed anticancer activities by sources capable of producing acrolein and
      hydroxyl radical. This hypothesis obvious implication: spermine enzymatic
      oxidations or other biochemical interactions that would co-generate acrolein and
      hydroxyl radical, the anticancer system components, should be tried as treatments
      for any given cancer. The biochemical generation of acrolein observed was totally
      unexpected, since this aldehyde was known; as a very toxic and highly reactive
      xenobiotic chemical produced in the pyrolysis of fats and other organic material,
      found as an atmospheric pollutant, in tobacco smoke and car emissions, and mainly
      used as a pesticide or aquatic herbicide. Numerous studies on acrolein,
      considered after our work a biological product, as well, followed. In them,
      acrolein widespread presence, its effects on diverse cellular proteins, such as,
      growth factors, and its anticancer activities, were additionally reported.
      Regarding hydroxyl radical, the second component of the proposed anticancer
      system, and another cytotoxic product in normal cell metabolism, it co-generates
      with acrolein in several biochemical interactions, occurrences suggesting that
      these products might jointly fulfill some biological role. Furthermore, hydroxyl
      radical shares with phosphoramide mustard, anticancer activities and many similar
      effects against DNA, including the production of damages resulting in mutagenesis
      and carcinogenesis, facts that led us to consider this radical, a biological
      counterpart of phosphoramide mustard. A physiological system involving acrolein
      and hydroxyl radical, consequently, will be expected to produce effects similar
      to those from acrolein and phosphoramide mustard, the main anticancer metabolites
      from the widely used drug, cyclophosphamide.

PMID- 22874454
TI  - Cochleovestibular nerve involvement in multifocal fibrosclerosis.
AB  - OBJECTIVES: To report a case of multifocal fibrosclerosis with a nine-year follow
      up, and to discuss this disease's radiological appearance and management. The
      disease is a rare systemic disorder of unknown cause characterised by fibrous
      proliferation involving multiple anatomical sites. CASE REPORT: A 50-year-old
      woman presented with histological findings characterised by similar inflammatory
      processes involving the meninges, pituitary gland, peritoneum, retroperitoneum
      and orbits, prompting a search for a common pathophysiology. A diagnosis of
      multifocal fibrosclerosis was postulated. Symptom improvement was noted after
      treatment with prednisone and azathioprine. CONCLUSION: This is the first
      documented case of involvement of the cochleovestibular nerve in a patient with
      multifocal fibrosclerosis. The rare association between fibrotic diseases and
      masses showing various clinical patterns should be kept in mind by
      otolaryngologists, and imaging performed to investigate for multifocal
      fibrosclerosis. However, diagnosis can only be confirmed with tissue biopsy and
      histopathological examination.

PMID- 22874455
TI  - Dietary patterns: a novel approach to examine the link between nutrition and
      cognitive function in older individuals.
AB  - Cognitive decline may lead to dementia whose most frequent cause is Alzheimer's
      disease (AD). Among the many potential risk factors of cognitive decline and AD,
      diet raises increasing interest. Most studies considered diet in the frame of a
      single nutrient approach with inconsistent results. A novel approach to examine
      the link between nutrition and cognitive function is the use of dietary patterns.
      The aim of the present review was to update and complete the body of knowledge
      about dietary patterns in relationship with various cognitive outcomes in the
      elderly. Two approaches can be used: a priori and a posteriori patterns. A priori
      patterns are defined by the adhesion to a pre-defined healthy diet using a score
      such as the Mediterranean diet (MeDi) score, the Healthy Eating Index, the
      Canadian Healthy Eating Index, the French National Nutrition and Health Programme
      (Programme National Nutrition Sante) Guideline Score (PNNS-GS), the Recommended
      Food Score (RFS) and Dietary Approaches to Stop Hypertension (DASH). MeDi score,
      RFS, PNNS-GS and DASH have been associated with lower risks of cognitive
      impairment, cognitive decline, and dementia or AD. Principal components analysis,
      reduced rank regression and clustering methods allow the identification of
      'healthy' patterns associated with lower risk of cognitive decline. However, some
      studies did not report any associations with cognitive outcomes and results are
      discordant especially regarding MeDi and the risk of dementia. Several
      methodological challenges should be overcome to provide a higher level of
      evidence supporting the development of nutritional policies to prevent cognitive
      decline and AD.

PMID- 22874456
TI  - New endemic West Nile virus lineage 1a in northern Italy, July 2012.
AB  - We report here the first blood donation positive for West Nile virus (WNV) by
      nucleic acid amplification testing collected in north-eastern Italy in July
      2012.Partial sequencing of the WNV RNA demonstrated identity with a WNV lineage
      1a genome identified in the same area in 2011 and divergence from the strain
      responsible for the outbreak in northern Italy in 2008-09. These data indicate
      that WNV activity in northern Italy is occurring earlier than expected and that
      different WNV strains are circulating.

PMID- 22874457
TI  - Did public health travel advice reach EURO 2012 football fans? A social network
      survey.
AB  - We posted a survey on the Union of European Football Associations (UEFA)'s EURO
      2012 Facebook profile to evaluate whether public health travel advice,
      specifically on the importance of measles vaccination,reached fans attending EURO
      2012. Responses suggested that these messages were missed by 77% of fans. Social
      networks could serve as innovative platforms to conduct surveys, enabling rapid
      access to target populations at low cost and could be of use during upcoming mass
      gatherings such as the Olympics.

PMID- 22874458
TI  - Infectious disease surveillance for the London 2012 Olympic and Paralympic Games.
AB  - The London 2012 Olympic and Paralympic Games will be one of the largest mass
      gathering events in British history. In order to minimise potential infectious
      disease threats related to the event, the Health Protection Agency (HPA) has set
      up a suite of robust and multisource surveillance systems. These include
      enhancements of already established systems (notification of infectious diseases,
      local and regional reporting,laboratory surveillance, mortality surveillance,
      international surveillance, and syndromic surveillance in primary care), as well
      as new systems created for the Games (syndromic surveillance in emergency
      departments and out-of-hours/unscheduled care,undiagnosed serious infectious
      illness surveillance).Enhanced existing and newly established surveillance
      systems will continue after the Games or will be ready for future reactivation
      should the need arise. In addition to the direct improvements to surveillance,
      the strengthening of relationships with national and international stakeholders
      will constitute a major post-Games legacy for the HPA.

PMID- 22874459
TI  - A new surveillance system for undiagnosed serious infectious illness for the
      London 2012 Olympic and Paralympic Games.
AB  - A new surveillance system was developed to detect possible new or emerging
      infections presenting as undiagnosed serious infectious illness (USII) for use
      during the London 2012 Olympic and Paralympic Games. Designated clinicians in
      sentinel adult and paediatric intensive care units (ICU/ PICUs) reported USII
      using an online reporting tool or provided a weekly nil notification. Reported
      cases were investigated for epidemiological links. A pilot study was undertaken
      for six months between January and July 2011 to evaluate the feasibility and
      acceptability of the system. In this six-month period, 5 adults and 13 children
      were reported by six participating units (3 ICUs, 3 PICUs). Of these 18 patients,
      12 were reported within four days after admission to an ICU/PICU. Nine patients
      were subsequently diagnosed and were thus excluded from the surveillance.
      Therefore, only nine cases of USII were reported. No clustering was identified.On
      the basis of the pilot study, we conclude that the system is able to detect cases
      of USII and is feasible and acceptable to users. USII surveillance has been
      extended to a total of 19 sentinel units in London and the south-east of England
      during the London 2012 Olympic and Paralympic Games.

PMID- 22874460
TI  - Is the basic reproductive number (R(0)) for measles viruses observed in recent
      outbreaks lower than in the pre-vaccination era?

PMID- 22874464
TI  - Epidemiological changes in cutaneous melanoma: retrospective study of 969 cases
      (1996-2010).
AB  - BACKGROUND: The incidence of malignant melanoma has increased over recent decades
      all over the world; however, we are not aware if this also occurs in Madrid. Our
      objective was to analyze epidemiological changes in cutaneous malignant melanomas
      diagnosed over a 15-year period. PATIENTS AND METHODS: Retrospective analysis of
      data of patients with primary cutaneous melanomas attended at Hospital Gregorio
      Maranon, Madrid, Spain, between 1996 and 2010, divided into three periods: 1996
      2000; 2001-2005; 2006-2010, was obtained. RESULTS: In total, 969 melanomas were
      histologically diagnosed. The mean age at the moment of diagnosis was 58.5 years
      old. The mean tumor thickness was 1.61 mm. The most common histological type was
      surface-spreading melanoma and the most common site was the trunk. There were
      statistically significant differences (P < .05) between the three periods of the
      study: older age at diagnoses (P < .001); larger number of head and neck
      melanomas (P < .001); more melanomas on trunk in women (P < .001); increase of
      lentigo maligna melanoma (P < .001); thinner mean tumor thickness (Breslow index)
      (P < .001); larger number of melanomas in situ (P < .001). However, thick
      melanomas (tumor thickness over 2 mm) ratio was still over 20% in all periods,
      especially in males and in those over 65 years old. CONCLUSIONS: Diagnosis of
      cutaneous melanoma in Spain is made increasingly with a thinner mean tumor
      thickness, although thick melanomas are still diagnosed in men and in individuals
      over 65 years.

PMID- 22874465
TI  - Evaluation of plant sterol intake estimated with the Northern Sweden FFQ.
AB  - OBJECTIVE: To evaluate plant sterol intake estimated with the eighty-four-item
      Northern Sweden FFQ against repeated 24 h dietary recalls (24-HDR) as the
      reference method. DESIGN: Randomly recruited participants from the Vasterbotten
      Intervention Programme (VIP) responded to an FFQ (FFQ1). Over the subsequent 12
      months, ten repeated 24-HDR were carried out. After this, a second FFQ (FFQ2) was
      completed. SETTING: Vasterbotten county, northern Sweden. SUBJECTS: Ninety-six
      men and ninety-nine women. RESULTS: The Pearson correlation coefficient for
      absolute total plant sterol intake estimated with FFQ1 and 24-HDR was 0.58 and
      0.55 for the men and women, respectively. Cross-classification of participants
      into quartiles of absolute plant sterol intake estimated with FFQ1 and 24-HDR
      showed that 90% of the men and 83% of the women were classified into the same or
      an adjacent quartile. For energy-adjusted plant sterol intake, 71% of the men and
      74% of the women were classified into the same or an adjacent quartile. The
      agreement for cross-classification of participants into quartiles between FFQ1
      and FFQ2 was good for both absolute and energy-adjusted plant sterol intake.
      CONCLUSIONS: The FFQ is able to capture absolute plant sterol intake to the same
      extent as other nutrients, and to rank individuals according to both their
      absolute and energy-adjusted plant sterol intake. The reproducibility of the FFQ
      was good, suggesting that the method is reliable. This makes it possible to use
      plant sterol data from the FFQ in large-scale studies of the association between
      plant sterol intake and disease.

PMID- 22874466
TI  - IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.
AB  - RATIONALE: A high-fat diet accompanied by hypertriglyceridemia increases an
      individual's risk for development of atherosclerosis. An early event in this
      process is monocyte recruitment through binding to vascular cell adhesion
      molecule 1 (VCAM-1) upregulated on inflamed arterial endothelium. Diets high in
      polyunsaturated fatty acids (PUFAs) may provide athero-protection by ameliorating
      this effect. OBJECTIVE: We investigated the acute regulation of VCAM-1 expression
      in human aortic endothelial cells (HAEC) in response to triglyceride-rich
      lipoproteins (TGRL) isolated from subjects after consumption of a high-fat meal.
      METHODS AND RESULTS: Postprandial TGRL isolated from 38 subjects were categorized
      as proatherogenic or antiatherogenic according to their capacity to alter the
      inflammatory response of HAEC. Proatherogenic TGRL increased expression of VCAM
      1, intercellular adhesion molecule 1 (ICAM-1), and E-selectin by ~20% compared
      with stimulation with tumor necrosis factor-alpha alone, whereas antiatherogenic
      TGRL decreased VCAM-1 expression by ~20% while still upregulating ICAM-1. The
      relative atherogenicity of TGRL positively correlated with particle density of
      TG, apolipoprotein (Apo)CIII, ApoE, and cholesterol. Omega3-PUFA mimicked the
      effect of antiatherogenic TGRL by downregulating VCAM-1 expression. TGRL exerted
      this differential regulation of VCAM-1 by reciprocally modulating expression and
      activity of the transcription factor interferon regulatory factor 1 (IRF-1) and
      expression of microRNA 126 (miR-126). Overexpression or silencing of IRF-1 or miR
      126 expression recapitulated the proatherogenic or antiatherogenic regulation of
      VCAM-1. CONCLUSIONS: In response to a high-fat meal, TGRL bias the inflammatory
      response of endothelium via transcriptional and posttranscriptional editing of
      VCAM-1. Subjects with an anti-inflammatory response to a meal produced TGRL that
      was enriched in nonesterified fatty acids, decreased IRF-1 expression, increased
      miR-126 activity, and diminished monocyte arrest.

PMID- 22874468
TI  - Living with pleasure in daily life at the end of life: recommended care strategy
      for cancer patients from the perspective of physicians and nurses.
AB  - OBJECTIVE: One of the most important goals of palliative care is achieving a good
      death. Most Japanese believe that "having some pleasure in daily life" is
      necessary at the end of life. The aim of this study was to identify, from the
      perspective of physicians and nurses, a care strategy that ensures that cancer
      patients have pleasure in daily life at the end of life. METHOD: We conducted
      semistructured interviews with experts in palliative care units. A total of 45
      participants included 22 palliative care physicians and 23 nurses. Transcripts of
      the interviews were analyzed using a content analysis method. RESULTS: Care for
      end-of-life cancer patients that ensures they have some pleasure in daily life
      was classified into five categories: "Pain assessment and pain easing" aimed to
      offer physical and psychological pain assessment and relief. "Maintenance of
      recuperative environment" aimed to offer care that arranged for assistive devices
      and equipment in the patient's room. "Support of daily life" aimed to offer care
      that eased accomplishment of daily activities. "Care that respects individuality"
      aimed to offer care that assessed sources of pleasure for the patient. "Events
      and complementary and alternative therapies" aimed to offer such care as
      aromatherapy and massage. SIGNIFICANCE OF RESULTS: The elements of care
      identified in this study are useful for all end-of-life cancer patients, even
      those who do not enter palliative care units. The next step of research is to
      test the efficacy of interventions that reflect the five identified categories of
      care for end-of life cancer patients.

PMID- 22874467
TI  - Effects of echinomycin on endothelin-2 expression and ovulation in immature rats
      primed with gonadotropins.
AB  - Echinomycin is a small-molecule inhibitor of hypoxia- inducible factor-1 DNA
      binding activity, which plays a crucial role in ovarian ovulation in mammalians.
      The present study was designed to test the hypothesis that hypoxia-inducible
      factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian
      ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin
      induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found
      to significantly decrease in the ovaries after echinomycin treatment, while HIF
      1alpha mRNA and protein expression was not obviously changed. Further analysis
      also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity
      in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the
      granulosa cells with gonadotropin and echinomycin treatments. The results of HIF
      1alpha and ET-2 expression in the granulosa cells transfected with cis-element
      oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF
      1alpha directly mediated the transcriptional activation of ET-2 during
      gonadotropin- induced superuvulation. Taken together, these results demonstrated
      that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important
      mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.

PMID- 22874469
TI  - Acid-base status and progression of chronic kidney disease.
AB  - PURPOSE OF REVIEW: Most patients with reduced glomerular filtration rate (GFR)
      have progressive GFR decline despite currently recommended kidney-protective
      interventions. Recent studies support that dietary acid reduction with Na(+)
      based alkali or food types that yield base when metabolized provides kidney
      protection that is additive to currently recommended interventions. We review
      these recent studies in light of current kidney-protective recommendations for
      chronic kidney disease (CKD). RECENT FINDINGS: Animal models of CKD show that
      metabolic acidosis and/or dietary acid induce intrakidney mechanisms that cause
      kidney injury and mediate progressive GFR decline. Translational studies in
      patients show that NaHCO(3) ameliorates kidney injury in patients with CKD and
      reduced GFR, with and without metabolic acidosis; NaHCO(3) and base-inducing food
      types each ameliorate kidney injury in patients with reduced GFR without
      metabolic acidosis; and NaHCO(3) and Na(+) citrate each slow GFR decline in CKD
      patients with reduced GFR, with and without metabolic acidosis. SUMMARY: Recently
      published studies in animals and humans suggest that acid-base-related mechanisms
      mediate nephropathy progression. These studies support that dietary acid
      reduction with Na(+)-based alkali or alkali-inducing food is an effective kidney
      protective adjunct to current strategies and support re-examination of current
      recommendations for CKD management.

PMID- 22874470
TI  - Current world literature.

PMID- 22874472
TI  - Hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a common inherited cardiovascular disease present
      in one in 500 of the general population. It is caused by more than 1400 mutations
      in 11 or more genes encoding proteins of the cardiac sarcomere. Although
      hypertrophic cardiomyopathy is the most frequent cause of sudden death in young
      people (including trained athletes), and can lead to functional disability from
      heart failure and stroke, the majority of affected individuals probably remain
      undiagnosed and many do not experience greatly reduced life expectancy or
      substantial symptoms. Clinical diagnosis is based on otherwise unexplained left
      ventricular hypertrophy identified by echocardiography or cardiovascular MRI.
      While presenting with a heterogeneous clinical profile and complex
      pathophysiology, effective treatment strategies are available, including
      implantable defibrillators to prevent sudden death, drugs and surgical myectomy
      (or, alternatively, alcohol septal ablation) for relief of outflow obstruction
      and symptoms of heart failure, and pharmacological strategies (and possibly
      radiofrequency ablation) to control atrial fibrillation and prevent embolic
      stroke. A subgroup of patients with genetic mutations but without left
      ventricular hypertrophy has emerged, with unresolved natural history. Now, after
      more than 50 years, hypertrophic cardiomyopathy has been transformed from a rare
      and largely untreatable disorder to a common genetic disease with management
      strategies that permit realistic aspirations for restored quality of life and
      advanced longevity.

PMID- 22874473
TI  - Single-stage Anterior Release and Sequential Posterior Fusion for Irreducible
      Atlantoaxial Dislocation.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To introduce the method of single
      stage anterior release and reduction with posterior fusion in irreducible
      atlantoaxial dislocation (IAAD) and to evaluate the clinical effects of this
      surgery. SUMMARY OF BACKGROUND DATA: In previous clinical studies, several
      techniques have been introduced to manage IAAD. But all these treatments have
      intrinsic disadvantages. A single-stage anterior release and reduction with
      posterior fusion can offer a new alternative which can avoid these disadvantages.
      METHODS: From January 2003 to January 2009, 22 cases of IAAD were diagnosed
      consecutively. Anterior atlantoaxial release was performed through anterior
      retropharyngeal approach, after traction reduction conducted on the monitoring of
      C-arm fluoroscopy. C1-C2 were then fixed posteriorly and fused by single stage.
      Neurological status was evaluated using the Japanese Orthopaedic Association
      scoring system. RESULTS: All patients were observed for an average of 32 months,
      ranging from 15 to 40 months. All cases achieved anatomic reduction and solid
      fusion. The Japanese Orthopaedic Association score of 12 patients with myelopathy
      improved from 8.3 to 13.9, 6 months postoperatively, and the mean improving rate
      was 87.5%. No graft or implant-related complications were observed in any patient
      during the entire follow-up period. CONCLUSIONS: The method of single-stage
      anterior release and reduction with posterior fusion is an effective method for
      management of IAAD, proving its value as a technique for achieving complete
      reduction with solid bony fusion.

PMID- 22874474
TI  - Refugia within refugia as a key to disentangle the genetic pattern of a highly
      variable species: the case of Rana temporaria Linnaeus, 1758 (Anura, Ranidae).
AB  - Two distinct lineages of Rana temporaria are known in the Palaearctic region, but
      it is uncertain whether this species persisted in one or more Pleistocene
      refugia. We resolved the phylogeographic history and genetic variability of R.
      temporaria in the Italian peninsula, a 'traditional' Pleistocene refugium, and
      related our findings to patterns described for other European populations. We
      sequenced the mitochondrial markers Cox I and cytochrome b. Phylogenetic
      reconstruction only indicated the presence of haplotypes belonging to the Western
      lineage in the Italian peninsula. Overall, the genetic variability of Italian
      populations was higher than other European populations, which shared haplotypes
      with the Alpine populations. We demonstrated subdivision into five main Italian
      sublineages, which was associated with a geographical structure of populations in
      two divergent groups. In particular, one Apennine group might have resulted from
      bottlenecks during the last interglacials ages. In contrast, Alpine populations
      were recently diverged and showed incomplete lineage sorting. Our data indicate
      that the Italian peninsula served as refugium for the Western lineage of R.
      temporaria. Dispersion towards Central Europe probably started only from the
      western slope of the Alps via a rapid leading edge expansion. The identified
      structure is partially congruent with traditional peripheral refugia identified
      for plants. This evolutionary scenario does not support any taxonomic distinction
      at the subspecific level for R. temporaria.

PMID- 22874475
TI  - The role of glia in late-life depression.
AB  - Late-life depression (LLD) has a complex and multifactoral etiology. There is
      growing interest in elucidating how glia, acting alone or as part of a glial
      neuronal network, may contribute to the pathophysiology of depression. In this
      paper, we explore results from neuroimaging studies showing gray-matter volume
      loss in key frontal and subcortical structures implicated in LLD, and present the
      few histological studies that have examined neuronal and glial densities in these
      regions. Compared to results in younger people with depression, there appear to
      be age-dependent differences in neuronal pathology but the changes in glial
      pathology may be more subtle, perhaps reflecting a longer-term compensatory
      gliosis to earlier damage. We then consider the mechanisms by which both
      astrocytes and microglia may mediate and modulate neuronal dysfunction and
      possible degeneration in depression. These include a critical role in the
      response to peripheral inflammation and central microglial activation, as well as
      a key role in glutamate metabolism. Advances in our understanding of glia are
      highlighted, including the role of microglia as "electricians" of the brain and
      astrocytes as key communicating cells, an integral part of the tripartite
      synapse. Finally, implications for clinicians are discussed, including the
      consideration of glia as biomarkers for LLD and incorporation of glia into future
      therapeutic strategies.

PMID- 22874476
TI  - Brain natriuretic peptide level in a small series of children and grown-ups with
      congenital heart defects with chronic cardiac failure.
AB  - The present study assessed the usefulness of brain natriuretic peptide in
      evaluating the cardiovascular status in children and grown-ups with congenital or
      acquired disease affected by chronic cardiac failure. Brain natriuretic peptide
      should be included in the risk stratification of children with dilated
      cardiomyopathy. In patients with congenital heart defects, it is useful to tailor
      the optimal medical strategy to individual patients.

PMID- 22874477
TI  - A rare case of spontaneous thyroid cyst haemorrhage.
AB  - BACKGROUND: We report a case of hypopharyngeal swelling secondary to a
      spontaneous thyroid cyst haemorrhage. Haemorrhage is a known complication of
      thyroid cysts, and usually presents as external swelling and localised pain. CASE
      REPORT: A 93-year-old woman developed hypopharyngeal swelling, dysphagia and
      odynophagia. A computed tomography scan was consistent with thyroid cyst
      haemorrhage. The patient was treated with needle aspiration and intravenous
      steroid injections, with full recovery at thyroid clinic review. CONCLUSION: To
      our best knowledge, there has been no previous report of a hypopharyngeal
      swelling occurring secondary to spontaneous thyroid cyst haemorrhage. Our case is
      unusual because of the risk of airway compromise at the level of the hypopharynx,
      secondary to thyroid cyst haemorrhage.

PMID- 22874478
TI  - Viral load monitoring in resource-limited settings:  a medical and public health
      priority.

PMID- 22874479
TI  - Immunoglobulin A-dominant postinfectious glomerulonephritis in a patient with
      acute HIV syndrome.

PMID- 22874480
TI  - Central nervous system HIV replication and HIV-related pachymeningitis in a
      patient on protease inhibitor monotherapy despite an undetectable plasma viral
      load.

PMID- 22874482
TI  - Assessing the impact of prevalent tuberculosis on mortality among antiretroviral
      treatment initiators:  accurate tuberculosis diagnosis is essential.

PMID- 22874484
TI  - Mediterranean diet: the whole is more than the sum of its parts.

PMID- 22874483
TI  - Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) level in hemodialysis
      patients and parameters affecting that level.
AB  - BACKGROUND: Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF
      (epidermal growth factor)-domain-containing protein 1 (SCUBE1) is a cell surface
      protein belonging to the SCUBE gene family. SCUBE1 has been shown to rise in
      parallel with platelet activation in acute ischemic events. However, there are no
      studies showing levels in the hemodialysis patient group, in which there is known
      to be an increase in platelet function impairment and activation. The purpose of
      this study was to investigate SCUBE1 levels in a hemodialysis patient group and
      the factors affecting those levels. MATERIALS AND METHODS: One hundred three
      hemodialysis patients and 21 age-matched healthy controls were included. SCUBE1
      and sCD40L levels were investigated from blood specimens collected on pre- and
      post-hemodialysis sessions. We investigated the correlation between SCUBE1 levels
      and sCD40L, patients' demographic data, parameters with hemodialysis treatment
      and routine biochemical tests. RESULT: SCUBE1 levels were significantly higher in
      the hemodialysis patient group compared with the controls (p=0.000). There was a
      significant rise in SCUBE1 levels in the post-hemodialysis session (p=0.000). We
      determined a positive correlation between SCUBE1 and sCD40L (p=0.016, r=0.215).
      Gender, blood pressure, BUN, creatinine, hematocrit and high-sensitivity C
      reactive protein (hsCRP) levels, hemodialysis membrane surface area, amount of
      ultrafiltration, blood flow rate, dialysis flow rate and carnitine use
      significantly affected SCUBE1 levels. CONCLUSION: We have shown, for the first
      time in the literature, that SCUBE1 level, a potential acute ischemia marker, is
      elevated in hemodialysis patients with no clinical ischemic event, and that
      various factors affect this elevation.

PMID- 22874485
TI  - The IDEAL study : towards personalized drug treatment of hypertension.
AB  - OBJECTIVE: To identify markers (phenotypic, genetic, or environmental) of blood
      pressure (BP) response profiles to angiotensin converting enzyme inhibitors
      (ACEIs) and diuretics. METHODS: IDEAL was a crossover (two active and two wash
      out phases), double-blind, placebo-controlled trial. Eligible patients were
      untreated hypertensive, aged 25 to 70. After two visits, patients were randomized
      to one of four sequences. The main outcome was BP differences between the active
      treatment and placebo. RESULTS: One hundred and twenty-four patients were
      randomised: mean age 53, men 65%, family history of hypertension 60%. Average BP
      fall at each visit before randomisation was about 2% of the initial level
      reflecting both a regression to the mean and a placebo effect. CONCLUSION: The
      results are expected to improve knowledge in drug's mechanisms of action and
      pathophysiology of hypertension, and to help in personalizing treatment. The
      estimation of BP responses to each drug in standardized conditions provided a
      benefit to each participant.

PMID- 22874486
TI  - [Evaluation of prescription practices for drugs charged in addition to DRG-based
      fees in Alsace].
AB  - Two studies led in parallel from May till June, 2009, were proposed in Alsace in
      order to analyze the hospital practices of prescription relative to 6 drugs
      charged in addition to the GHS: bevacizumab, gemcitabine, trastuzumab,
      etanercept, adalimumab and infliximab. The first study, led within 9 hospitals,
      allowed the collection of 343 situations of prescription. The second approach,
      based on the extraction of the PMSI data from the same hospitals, allowed the
      exploitation of 771 situations of prescription. The data collected on sites and
      from the PMSI respectively put in evidence 86.3% and 73.0% of prescriptions
      corresponding to guidelines. No unacceptable situation was revealed. The
      differences between approaches can be explained by the important proportion of
      unclassifiable situations extracted from the PMSI. These approaches bring
      complementary lightings and allow the OMEDIT of Alsace to take position in its
      missions of expertise and follow-up of therapeutic innovations.

PMID- 22874487
TI  - [Neuroenhancement in healthy subject? A French case study].
AB  - Neuroenhancement is an anglo-saxon concept concerning the use of stimulating
      psychotropic drugs by healthy subjects, outside any established medical
      indication or festive setting, to achieve an improvement of their mental
      functioning. In 2009, because of increasing requests for neuroenhancement in USA,
      the American Association of Neurology has published practical recommendations
      stating that "it is ethically permissible to prescribe medications for
      neuroenhancement" if a number of conditions is met. We present these ethical and
      psychopharmacological conditions ("the inverted U-Shape principle" in which
      cognitive performance is related to catecholamine levels and "the trade-off
      principle" to cognitive enhancement) through a clinical case of methylphenidate
      prescription in a healthy 24 years old medical student, preparing for the "examen
      classant national" (the French national ranking before postgraduate education).
      We then discuss anglo-saxon ethical context in which these recommendations have
      been proposed.

PMID- 22874488
TI  - [Psychiatric disorders associated with high-dose methadone (>100 mg/d): a
      retrospective analysis of treated patients].
AB  - BACKGROUND: Recent studies show that high-dose methadone (>100 mg/d) allow a
      better control of the consumptions of illicit opiates by treated patients.
      OBJECTIVE: The aim of this retrospective study was to analyze data of patients
      requiring high-dose methadone (>100 mg/d) as well as associated factors. METHODS:
      We retrospectively reviewed charts of treated patients with high-dose methadone
      followed in the maintenance methadone treatment center between 01/01/07 and
      01/07/10. The following variables (medical history, psychiatric comorbidities,
      associated drugs, and polyaddictions), were assessed with high-dose methadone,
      using an univariate and then a multavariate analysis. The threshold value of 130
      mg/day (median of maximal daily dose) was used to perform analysis. RESULTS:
      During the study period, 78 patients, mainly men (75.6%), with a median age of 34
      years [22-57] were included. The both groups with posology of methadone <= 130
      mg/d (n=44) versus posology of methadone >130 mg/d (n=34) were close in term of
      demographic characteristics, consumption of drugs and associated treatments.
      Plasma methadone concentrations were higher in patients with the daily doses of
      methadone superior than 130 mg/d (NS), as well as the methadone metabolite (EDDP,
      p=0.048). Among studied factors, the presence of psychiatric comorbidities was
      significantly associated with high-dose methadone (threshold 130 mg/d) [OR 4,6 IC
      95% (1.412;14.925)]. Seven patients presented with complications related to
      methadone: cardiac disorder (3), libido troubles (3) and hypofertility (1).
      CONCLUSION: Patients requiring high-dose methadone are polydrug addicts. In our
      study, patients with psychiatric comorbidities needed daily dose of methadone
      significantly more raised.

PMID- 22874489
TI  - [Could we improve notification of adverse drugs reactions in hospital? Assessment
      of 5 years of network PharmacoMIP's activities].
AB  - BACKGROUND: Spontaneous reporting of adverse drug reactions (ADR) is fundamental
      to drug safety surveillance (pharmacovigilance) and assessment of benefit/risk
      ratio. However, under-reporting remains the limit of the system. OBJECTIVE: The
      aim of this study was to assess the effect of regular visits of an Assistant in
      Clinical Research (CRA) on the improvement of ADR reporting in non-university
      hospitals. METHODS: We set up an ADR report collecting system that involved
      regular visits in non-university hospitals, We began the visits in 2006 in 2
      areas (Haute Garonne and Gers), extended to 4 other areas in 2009. We compared
      the reporting rate (number of reports/number of beds) of total ADRs reported by
      non-university hospitals in these areas before (one year) and after the start of
      CRA visits. RESULTS: A total 2831 of reports were collected by the CRA: 40% were
      "serious" including two deaths. The results suggest an increase of 100% of the
      rate of reporting of ADRs. CONCLUSION: This study shows that regular visits
      increases the number of ADRs reported by non-university hospitals. Further
      assessment of this procedure is necessary for long term evaluation of its
      effectiveness.

PMID- 22874490
TI  - [A general practitioner's one year record of adverse drug reactions].
AB  - OBJECTIVES: To systematically record and analyse every adverse drug reaction
      (ADR) observed by one general practitioner (GP) over the course of one year of
      practice. METHODS: Every ADR reported by patients, or discovered upon
      questioning, was collected and classified as either serious or non serious and as
      labelled or unlabelled. Suspected drugs were classified according to their
      pharmacological group, therapeutic class and medical specialty. RESULTS: We
      observed 163 ADRs for 7074 medical acts (2.29 per 100 consultations). Of these,
      12 were serious and labelled, 5 non serious and unlabelled (0.17 and 0.07 per
      100, respectively). Ninety drugs were involved. Of the 34 therapeutic classes
      involved analgesics accounted for 30.1% of ADRs. Of the 57 pharmacological groups
      opiates were associated with 18.5% of ADRs. Among the 18 medical specialties,
      rheumatology accounted for 33.1% of ADRs. Based on the data collected, the
      average French GP could be expected to report 9.8 ADRs per year (6.9 serious and
      2.9 unlabelled), resulting potentially in 388,502 serious ADRs reported in France
      annually, in contrast to the 759 actually declared in 2008. CONCLUSION: Under
      reporting of ADRs by GP is confirmed. Mainly analgesics and opiates are
      concerned. Serious and unlabelled AEs could be better recorded and reported by
      GPs.

PMID- 22874492
TI  - [Summarizing of medicinal alerts in Ivory Coast from 2001 till 2010].
AB  - STUDY'S AIM: This study aims a more efficient follow-up of the safety of
      medicines with human usage on the Ivory Coast territory. METHOD: The structure
      responsible for pharmacovigilance in Ivory Coast i.e. DPM listed the medicinal
      alerts from 2001 till 2010. RESULTS: It emerges 237 medicinal alerts among which
      145 stops of marketing, 55 withdrawals of lots, 33 information notes and 4
      levying of suspension of medicines. These alerts result mainly from
      pharmaceutical companies (49%) and the French Drug Agency or ANSM (ex-Afssaps)
      (43%). They mainly concern drugs of infectious target (22%) and pneumology (18%)
      and their motivations are so much industrial with mainly commercial reasons (27%)
      as of pharmacovigilance dominated by unfavorable profit/risk connections.
      CONCLUSION: These results constitute an important database for the survey of the
      medicines market in Ivory Coast and an additional motivation to accelerate the
      implementation of a real national center of pharmacovigilance.

PMID- 22874491
TI  - [Clinical pharmacy and pharmacovigilance over a period of nine years in
      hospital].
AB  - INTRODUCTION: Underreporting is the main limit in any pharmacovigilance system
      relying on spontaneous notification. Available data emphasize that pharmacists
      report few adverse drug reactions (ADRs) in France. OBJECTIVE: To report how the
      integration of pharmacists in health care units contributes to reporting of ADRs
      and to study the validity of the reports. METHOD: Over a period of nine years we
      have prospectively collected and analyzed all ADRs collected by pharmacists in a
      university hospital setting and notified to the regional center of
      pharmacovigilance. RESULTS: Over the study period 2017 notifications were sent.
      Over the past four years the annual number of reports varied between 250 and 350.
      This amount is approximately ten times the number referred by physicians during
      the year preceding the beginning of this work. Only 8.6% of the submitted
      notifications were rejected by the pharmacovigilance center for various reasons:
      no causal link between the adverse event and taking medication, problem of
      timing, lack of data... CONCLUSION: The integration of the adverse reaction
      reporting in the daily activities of the pharmacist is a mean to increase very
      significantly the number of reports (factor of increase of 9.6 to 13.4).

PMID- 22874493
TI  - [News on infantile hemangioma therapy by beta-blocker].
AB  - Hemangiomas are benign tumors most commonly encountered in infancy and early
      childhood. While most of them regress spontaneously, some require treatment due
      to a significant proliferation, which may be complicated by ulceration,
      deformation aesthetic deformation or worse impairment vital. Among the treatments
      used corticosteroids is the standard treatment but its use in high doses expose
      to potential risks. In 2008, the discovery by "chance" of the effectiveness of
      propranolol in the management of hemangioma revolutionizes the first line
      treatment. Its mechanism of action is not yet well understood and establishment
      of such treatment should be done by a hospital paediatrician in the absence of
      any contraindications. This article proposes focus on effectiveness and tolerance
      of beta-blockers used as treatment of infantile hemangiomas.

PMID- 22874494
TI  - [Persistence of several days high levels of phenytoin and neurological symptoms
      during voluntary intoxication with Di-hydan((r))].

PMID- 22874495
TI  - [Antipsychotics in young adults as an indicator of the need for psychiatric
      care].

PMID- 22874497
TI  - The use of sports references in marketing of food and beverage products in
      supermarkets.
AB  - OBJECTIVE: Food marketing has been identified as a significant driver of the
      childhood obesity epidemic. The purpose of the present study was to (i) conduct a
      content analysis of the types of sports references that appear on supermarket
      food and beverage products and (ii) assess each product's nutritional and
      marketing profile. DESIGN: This was a descriptive study. Every product featuring
      sports references on the packaging was purchased in two major supermarkets during
      2010. A content analysis was conducted and nutritional evaluations were made
      based on the Nutrient Profile Model, a validated nutrition model. Marketing data
      were obtained from The Nielsen Company. SETTING: Two major supermarkets in
      Connecticut, USA. SUBJECTS: Food and beverage products (n 102) were selected from
      two supermarkets. RESULTS: The 102 products (fifty-three foods and forty-nine
      beverages) had sports references as part of their packaging: 72.5 % featured a
      character exercising, 42.2 % were endorsed by a professional sports entity and
      34.0 % were child-targeted. The median nutrition score for food products was 36
      (1 = unhealthiest and 100 = healthiest; scores of >=63 are considered healthy
      according to this model). More than two-thirds of beverages (69.4 %) were 100 %
      sugar-sweetened. Children saw significantly more commercials for these products
      than adults. CONCLUSIONS: Companies place sports figures on food and beverage
      products that are child-targeted and unhealthy.

PMID- 22874498
TI  - Long-range PCR and next-generation sequencing of BRCA1 and BRCA2 in breast
      cancer.
AB  - Individuals and families carrying mutations in BRCA1 and BRCA2 (BRCA1/2) have a
      markedly elevated risk of developing breast and ovarian cancers. The first
      generation of BRCA1/2 mutation analysis targeted only the coding exons and has
      implicated protein-truncating mutations (indel, nonsense) in BRCA1/2
      inactivation. Recently, heritable breast cancers have also been attributed to
      other exonic mutations (missense, silent) and mutations in introns and
      untranslated regions. However, analysis of these alterations has been
      prohibitively laborious and cost intensive, and the proportion of cases carrying
      mutations in unscreened regions of BRCA1/2 and other predisposition genes is
      unknown. We have developed and validated a next-generation sequencing (NGS)
      approach for BRCA1/2 mutation analysis by applying long-range PCR and deep
      sequencing. Genomic DNA from familial breast cancer patients (N = 12) were
      screened and NGS successfully identified all 19 distinct (51 total) BRCA1 and 35
      distinct (63 total) BRCA2 sequence alterations detectable by the Sanger
      sequencing, with no false-negative or positive results. In addition, we report
      the robust detection of variants from introns and untranslated regions. These
      results illustrate that NGS can provide comprehensive genetic information more
      quickly, accurately, and at a lower cost than conventional approaches, and we
      propose NGS to be a more effective method for BRCA1/2 mutational analysis.
      Advances in NGS will play an important role in enabling molecular diagnostics and
      personalized treatment of breast and ovarian cancers.

PMID- 22874499
TI  - The relationship of California's Medicaid reimbursement system to nurse staffing
      levels.
AB  - BACKGROUND: Policy initiatives at the Federal and state level are aimed at
      increasing staffing in nursing homes. These include direct staffing standards,
      public reporting, and financial incentives. OBJECTIVE: To examine the impact of
      California's Medicaid reimbursement for nursing homes which includes incentives
      directed at staffing. RESEARCH DESIGN: Two-stage limited-information maximum
      likelihood regressions were used to model the relationship between staffing
      [registered nurses (RNs), licensed practical nurses, and certified nursing
      assistants hours per resident day] and the Medicaid payment rate, accounting for
      the specific structure of the payment system, endogeneity of payment and case
      mix, and controlling for facility and market characteristics. SAMPLE: A total of
      927 California free-standing nursing homes in 2006. MEASURES: The model included
      facility characteristics (case-mix, size, ownership, and chain affiliation),
      market competition and excess demand, labor supply and wages, unemployment, and
      female employment. The instrumental variable for Medicaid reimbursement was the
      peer group payment rate for 7 geographical market areas, and the instrumental
      variables for resident case-mix were the average county revenues for professional
      therapy establishments and the percent of county population aged 65 and over.
      RESULTS: Consistent with the rate incentives and rational expectation behavior,
      expected nursing home reimbursement rates in 2008 were associated with increased
      RN staffing levels in 2006 but had no relationship with licensed practical nurse
      and certified nursing assistant staffing. The effect was estimated at 2 minutes
      per $10 increase in rate. CONCLUSIONS: The incentives in the Medicaid system
      impacted only RN staffing suggesting the need to improve the state's rate setting
      methodology.

PMID- 22874501
TI  - Should community-based services be publicly funded or contracted out?
AB  - OBJECTIVE: The introduction of Canada's Medicare in 1966 established precedence
      for a universally accessible and equitable healthcare system. Although Canada has
      been a leader in building the foundations of socialized medicine, it has stalled
      short of fulfilling a vision promulgated by its architects of a system that
      operates on a continuum of care. The aim of this review was to examine whether
      the expansion of publicly funded services under the Canada Health Act would be an
      economically and socially viable policy option. METHOD: A literature review of
      the direct and indirect social and economic costs associated with contracting out
      community-based services in the form of outpatient rehabilitative care,
      palliative care, and home care was conducted. RESULTS: This article concludes
      that the private financing of community-based services increases healthcare costs
      in the long term through increased density and frequency of acute care
      utilization. It is associated with increased indirect costs in the form of
      caregiver burden and reduced labor market participation of informal caregivers.
      The expansion of publicly funded community-based services minimizes these direct
      health and indirect societal costs. SIGNIFICANCE OF RESULTS: The integration of
      publicly funded community-based services under the Canada Health Act would ensure
      that the principles of Medicare in the form of equity and accessibility would be
      enforced while maintaining an economically sustainable healthcare system.

PMID- 22874502
TI  - Cellular uptake pathways of lipid-modified cationic polymers in gene delivery to
      primary cells.
AB  - Hydrophobic modifications have emerged as a promising approach to improve the
      efficiency of non-viral gene delivery vectors (GDV). Functional GDVs from non
      toxic polymers have been created with this approach but the mechanism(s) behind
      lipid-mediated enhancement in transfection remains to be clarified. Using a
      linoleic acid-substituted 2 kDa polyethylenimine (PEI2LA), we aimed to define the
      cellular uptake pathways and intracellular trafficking of plasmid DNA in normal
      human foreskin fibroblast cells. Several pharmacological compounds were applied
      to selectively inhibit uptake by clathrin-mediated endocytosis (CME), caveolin
      mediated endocytosis (CvME) and macropinocytosis. We found that PEI2LA complexes
      were taken up predominantly through CME, and to a lesser extent by CvME. In
      contrast, its precursor molecule, PEI2 complexes was internalized primarily by
      CvME and macropinocytosis. The commonly used 25 kDa PEI 25 complexes utilized all
      endocytic pathways, suggesting its efficiency is derived from a different set of
      transfection pathways than PEI2LA. We further applied several endosome disruptive
      agents and found that hypertonic media enhanced the transfection of PEI2LA by 6.5
      fold. We infer that lipid substitution changes the normal uptake pathways
      significantly and transfection with hydrophobically modified GDVs may be further
      enhanced by incorporating endosome disruptive elements into vector design.

PMID- 22874500
TI  - Effectiveness of long-term acute care hospitalization in elderly patients with
      chronic critical illness.
AB  - BACKGROUND: For patients recovering from severe acute illness, admission to a
      long-term acute care hospital (LTAC) is an increasingly common alternative to
      continued management in an intensive care unit (ICU). OBJECTIVE: To examine the
      effectiveness of LTAC transfer in patients with chronic critical illness.
      RESEARCH DESIGN: Retrospective cohort study in United States hospitals from 2002
      to 2006. SUBJECTS: Medicare beneficiaries with chronic critical illness, defined
      as mechanical ventilation and at least 14 days of intensive care. MEASURES:
      Survival, costs, and hospital readmissions. We used multivariate analyses and
      instrumental variables to account for differences in patient characteristics, the
      timing of LTAC transfer, and selection bias. RESULTS: A total of 234,799 patients
      met our definition of chronic critical illness. Of these, 48,416 (20.6%) were
      transferred to an LTAC. In the instrumental variable analysis, patients
      transferred to an LTAC experienced similar survival compared with patients who
      remained in an ICU [adjusted hazard ratio=0.99; 95% confidence interval (CI),
      0.96 to 1.01; P=0.27). Total hospital-related costs in the 180 days after
      admission were lower among patients transferred to LTACs (adjusted cost
      difference=-$13,422; 95% CI, -26,662 to -223, P=0.046). This difference was
      attributable to a reduction in skilled nursing facility admissions (adjusted
      admission rate difference=-0.591; 95% CI, -0.728 to -0.454; P<0.001). Total
      Medicare payments were higher (adjusted cost difference=$15,592; 95% CI, 6343 to
      24,842; P=0.001). CONCLUSIONS: Patients with chronic critical illness transferred
      to LTACs experience similar survival compared with patients who remain in ICUs,
      incur fewer health care costs driven by a reduction in postacute care
      utilization, however, invoke higher overall Medicare payments.

PMID- 22874503
TI  - Bilateral congenital choanal atresia encountered in late adulthood.
AB  - OBJECTIVE: We describe a case of bilateral congenital choanal atresia in the
      oldest patient reported with this condition in the recent English language
      literature. METHOD: Case report and a review of the relevant English language
      literature, presenting the embryopathogenesis, diagnostic methods and treatment
      options for this condition. RESULTS: A 53-year-old woman having difficulty with
      nasal breathing, and with a continuous nasal discharge, was admitted to our
      clinic. Bilateral congenital choanal atresia was diagnosed by endoscopic
      examination and paranasal sinus computed tomography. Surgical treatment used an
      endoscopic transnasal approach. The follow-up examination a year later revealed
      adequate choanal openings bilaterally. CONCLUSION: To our knowledge, this is the
      oldest patient with bilateral congenital choanal atresia to be reported in the
      recent literature. This condition is rarely encountered in adulthood but should
      be considered as a possible differential diagnosis of persistent nasal
      obstruction.

PMID- 22874504
TI  - [Retrospective analysis of the long-term indwelling ureteral stent].
AB  - An indwelling ureteral stent is commonly used for relief of ureteral obstruction.
      However, few reports have documented the frequency of febrile urinary tract
      infection and changes in renal function in patients with long-term ureteral stent
      placement. Here we report our experience with patients who had undergone long
      term placement of ureteral stents. Between January 2005 and March 2011, we
      performed exchange of ureteral stents in 25 patients for more than one year. The
      mean serum creatinine level at the baseline, after stent placement, and 1 year
      later was 2.10, 1.24, and 1.39 mg/dl, respectively. In 14 of the patients, 39
      episodes of febrile urinary tract infection occurred. Among a total of 1,055
      stent exchanges, 39 episodes (3.7%) of stent encrustation occurred. Two patients
      in whom stents had been forgotten suffered septic shock. The serum creatinine
      level following a long placement period did not change significantly, and of the
      patients whose hydronephrosis remained after stent placement, the risk of febrile
      urinary tract infection rises. Our results suggest that ureteral stents could be
      indwelt for a fairly long period of time without major complications as long as
      they were carefully followed up and regularly exchanged.

PMID- 22874505
TI  - [The factors for continuing docetaxel-based chemotherapy for castration-resistant
      prostate cancer].
AB  - A cohort of patients with castration-resistant prostate cancer (CRPC) that were
      treated with docetaxel (DOC) were retrospectively analyzed in order to examine
      the factors for continuing DOC therapy. In total, 26 patients treated with DOC at
      our hospital from August 2007 to August 2011 were recruited into the study. The
      participants were divided into two groups ; the first comprising 13 patients who
      received short-term DOC therapy (less than 5 cycles) and the second comprising 13
      who received long-term DOC therapy (5 or more cycles). There was no significant
      difference in the indicators including age, prostate specific antigen level (at
      initial diagnosis), clinical stage and Gleason score between the groups. Patients
      with pain or poor performance status were more likely to be found in the short
      term DOC group. The Hemoglobin-level was significantly higher in the long-term
      DOC group. In contrast, alkaline phosphatase, lactate dehydrogenase and C
      reactive protein levels were significantly higher in the short-term DOC group.
      The period from the start of primary endocrine therapy to CRPC diagnosis was
      significantly longer in the long-term DOC group (p=0.0008). This latter finding
      suggests that DOC therapy can be continued for a longer time, in CRPC cases which
      have a long-term response to endocrine therapy, and may be associated with a more
      favorable survival outcome. However, to validate this suggestion, further
      investigation with a larger cohort of cases is necessary.

PMID- 22874506
TI  - [A case of micropapillary bladder carcinoma].
AB  - A case of urothelial carcinoma containing micropapillary variant in the urinary
      bladder is reported. The micropapillary bladder carcinoma isa rare variant of
      urothelial carcinoma and has an aggressive clinical course. A 45-year-old man
      complained of hematuria in October, 2009. He visited a hospital and was diagnosed
      with a bladder tumor. Transurethral resection of the bladder tumor was performed
      at the hospital. The transurethral resection demonstrated poorly differentiated
      adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital.
      Our pathologist diagnosed the case as micropapillary variant of urothelial
      carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic
      lymph nodes dissection were performed. After the operation, he received three
      courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient
      remains free of tumor recurrence and metastasis for 28 months after the
      cystectomy.

PMID- 22874507
TI  - [A case report of placenta percreta with bladder invasion].
AB  - A 33-year-old British woman who had undergone caesarean section at 31 years of
      age was admitted to our hospital at 28 weeks of gestation due to a large amount
      of genital hemorrhage induced by total placenta previa. Magnetic resonance
      imaging showed placenta percreta with bladder invasion. To control the sudden
      hemorrhage at 31 weeks of gestation, we performed an operation emergently. An
      occlusion ballon was inserted into the bilateral internal iliac arteries by
      radiologists, caesarian section followed by simple hysterectomy was performed by
      gynecologists, and then the bladder wall with placenta percreta was removed by
      urologists. Although the operation was carefully undertaken with multi-department
      cooperation, 11,550 ml of blood was lost during the 6.5-hour operation. There are
      few reports of placenta percreta with bladder invasion, about 30 cases including
      3 cases in our country have been reported around the world until now.

PMID- 22874508
TI  - [A case of vesical endometriosis that worsened during the early pregnancy
      period].
AB  - We report a case of vesical endometriosis that worsened during the early
      pregnancy period. A 37-year old woman had been under treatment for endometriosis
      (including vesical endometriosis) by a gynecologist during the past 10 years. She
      was treated for sterility 1 year ago, and became pregnant through in vitro
      fertilization. In her 8th gestational week, she complained of gross hematuria at
      our hospital. Cystoscopic findings revealed some tumors that appeared worse than
      the last findings two years ago. In order to deny malignancy, transurethral
      resection of the bladder tumor was performed in her 12th gestational week. The
      pathologic diagnosis was endometriosis. She was able to stay pregnant, and
      delivered a girl. After delivery, cystoscopic findings revealed reduction of
      tumors. In most cases pregnancy cures endometriosis ; however, in this case
      symptoms became worse during the early stage of pregnancy. The reason for this
      contrary event is discussed.

PMID- 22874509
TI  - [A case of myxofibrosarcoma of the bladder].
AB  - A 43-year-old woman presented to our hospital with the chief complaints of gross
      hematuria and dysuria. Cystoscopy and magnetic resonance imaging showed a tumor
      on the dome of the bladder and large blood clots. Computed tomography
      demonstrated no findings of distant metastasis. Following transurethral resection
      of the tumor, the tumor was histologically diagnosed as myxofibrosarcoma with
      muscular invasion, and partial cystectomy was performed in September 2009. There
      has been no evidence of recurrence or metastasis for 24 months postoperatively.
      In addition, the Japanese literature on myxofibrosarcoma of the bladder was
      reviewed and discussed.

PMID- 22874510
TI  - [A case report on a patient with inflammatory pseudotumor of the bladder].
AB  - A 43-year-old man was referred to our hospital with a bladder tumor, which was
      incidentally found by abdominal ultrasonography in a health examination.
      Cystoscopy and magnetic resonance imaging showed a 3 cm submucosal bladder tumor
      localized at the top of the bladder. We performed transurethral resection of
      bladder tumor. Histopathological features was inflammatory tumor of urinary
      bladder. No local recurrence was seen 6 months after surgery.

PMID- 22874511
TI  - [Spindle cell sarcoma of the penis: a case report].
AB  - A 75-year-old man, with a past history of radiation therapy for prostatic
      carcinoma ten years ago, was referred to our hospital with complaints of penile
      tumor. After pathological examination by core biopsy, the patient was treated by
      radical penectomy for a penile tumor. Pathological examinations demonstrated that
      the tumor was composed of pleomorphic spindle cells without any differentiation
      tendency and diagnosed as spindle cell sarcoma. Although the patient had a past
      history of radiation therapy for the prostate, the causal relation of development
      of penile sarcoma with the radiation therapy was uncertain because the main tumor
      was very near but outside of the irradiation field. The sarcoma rarely occurs in
      the penis, and this is the first report of penile spindle cell sarcoma, to our
      knowledge.

PMID- 22874512
TI  - [Y-autosome translocation associated with male infertility: a case report].
AB  - A 40-year-old man was referred to our hospital with a 12-year history of
      infertility. He was a well developed male weighing 78 kg with a height of 171 cm.
      Physical examinations revealed male habitus with normal adult pubic and axillary
      hair. The penis, epididymides, spermatic cords and prostate were normal. The
      right testis was about 15 ml in volume and left ne was approximately 12 ml,
      respectively. Repeated semen analyses showed azoospermia except for only one time
      when 4 immotile sperm were detected. The plasma levels of lactate hydrogenase,
      follicle stimulating hormone prolactin and testosterone were within normal
      limits. Chromosome analysis of peripheral lymphocytes revealed a balanced
      reciprocal translocation between the short arm of chromosome 12 and the long arm
      of the Y chromosome (46, X, t (Y ; 12) (q12 ; p13.3)). We performed
      microdissection testicular sperm extraction and retrieved 11 spermatozoa (10
      progressive motile). Seminiferous epithelium showed maturation arrest at the
      stage of spermatid. Mean Johnsen's score count was 6. The etiology and clinical
      features of this rare disease were briefly discussed.

PMID- 22874513
TI  - Thalidomide for steroid-dependent immune reconstitution inflammatory syndromes
      during AIDS.
AB  - Management of relapsing or refractory immune reconstitution inflammatory
      syndromes (IRISs) despite corticosteroid therapy is yet to be defined. We
      describe three HIV-infected patients with corticosteroid-dependent and life
      threatening paradoxical immune reconstitution inflammatory syndrome for whom
      thalidomide treatment induced rapid clinical remission and permitted complete
      corticosteroid withdrawal without clinical relapse.

PMID- 22874515
TI  - Tenofovir-associated proteinuria.
AB  - Proteinuria was observed in 27% of 153 patients taking tenofovir for more than 1
      year. Concomitant protease inhibitor therapy and cumulative tenofovir exposure
      were independently associated with proteinuria in this cohort. Proteinuria was
      reversible in 11 of 12 patients who ceased tenofovir because of proteinuria
      without altering other medications. Clinicians should be aware that tenofovir can
      cause reversible proteinuria in patients with HIV.

PMID- 22874514
TI  - Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes
      on natural killer cell and T-cell function in HIV-1-infected controllers.
AB  - OBJECTIVE: Both protective T-cell genotypes and natural killer (NK) cell
      genotypes have been associated with delayed progression to AIDS and shown to be
      co-inherited in HIV-1-infected individuals who limit viral replication in absence
      of antiretroviral therapy ('controllers'). However, a comparative analysis of the
      genotype and function of the innate and adaptive immune compartments in HIV-1
      infected controller individuals has been understudied to date. DESIGN: Here, we
      simultaneously tested NK and T-cell function in controllers to investigate the
      mechanism(s) that might account for host immune control over viral replication.
      METHODS: We measured CD8 T-cell responses against HIV-1 utilizing overlapping 15
      mer peptides spanning the HIV-1 consensus clade B Gag protein and tested NK cell
      degranulation and cytokine secretion against tumor target cells following
      interferon-alpha (IFNalpha) stimulation. RESULTS: Among a cohort of 37
      controllers, the presence of protective major histocompatibility complex class I
      human leukocyte antigen (HLA) alleles (such as HLA-B*57) was not correlated with
      HIV-specific CD8 responses. In contrast, the inheritance of a protective killer
      inhibitory receptor KIR3DL1*h/*y receptor genotype along with the corresponding
      HLA-Bw4*80I ligand was associated with significantly heightened target cell
      induced NK degranulation and cytokine secretion following IFNalpha stimulation (P
      = 0.0201, n = 13). Interestingly, we observed a significant inverse association
      between the IFNalpha stimulated NK response to K562 cells and the HIV-specific
      CD8 T-cell response to Gag among elite controllers (rho = -0.8321, P = 0.0010, n
      = 12). CONCLUSION: Together, these results suggest that heightened NK responses
      can be evidenced independently of HIV-specific T-cell responses in HIV-1-infected
      elite controllers.

PMID- 22874516
TI  - Response to antiretroviral therapy in occult hepatitis B and HIV co-infection in
      West Africa.
AB  - This study evaluated the outcome of first-line antiretroviral therapy among 35
      Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120
      patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co
      infection. Increases in CD4 cell count and BMI were similar, whereas elevations
      of hepatic transaminases were more frequent in both the occult HBV and HBsAg+
      patients. Occult HBV/HIV co-infection appears not to impact adversely on response
      to antiretroviral therapy in Ghana.

PMID- 22874517
TI  - Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir
      decreases subcutaneous adipose tissue mitochondrial DNA.
AB  - OBJECTIVE: No randomized study has prospectively followed subcutaneous adipose
      tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside
      reverse transcriptase inhibitors (tNRTIs). DESIGN: The Metabolic Effects of
      DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment
      naive male participants to start lopinavir/ritonavir (LPVr) with either
      zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP). METHODS: Regional body fat
      was assessed by dual energy x-ray absorptiometry and abdominal computed
      tomography at months 0, 3, 12, 24 and 36. In a molecular substudy, subcutaneous
      adipose tissue (SAT) biopsies were taken, with mtDNA quantified by quantitative
      PCR. Data were analyzed using repeated measures linear regression analyses.
      RESULTS: Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy,
      and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months,
      the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3
      kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the
      LPVr/NVP group [131 cm (6.86) versus 146 cm (6.33), P = 0.097]. Over 36 months,
      mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell,
      P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the
      LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111)
      copies/cell, P = 0.65, between-group difference P < 0.01 for both measurements].
      mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months. CONCLUSION:
      This is the first randomized study to prospectively demonstrate reductions in SAT
      mtDNA in patients initiating ZDV/3TC-containing antiretroviral therapy (ART) but
      not in those initiating nucleoside reverse transcriptase inhibitor-sparing ART
      containing NVP and protease inhibitor. That reductions in SAT mtDNA were also
      accompanied by lower limb fat suggests that use of ART not containing ZDV/3TC may
      help prevent development of peripheral lipoatrophy.

PMID- 22874518
TI  - Effects of aging and smoking on carotid intima-media thickness in HIV-infection.
AB  - OBJECTIVES: To investigate the effects of aging and smoking on carotid intima
      media thickness (cIMT) among patients with and without HIV. METHODS: Data from a
      community sample of HIV-infected and HIV-uninfected participants were analyzed.
      Carotid intima-media thickness was measured via carotid ultrasound and smoking
      history was obtained via patient interview. RESULTS: Data on 166 male and female
      participants with stable HIV-infection and 152 healthy HIV-uninfected
      participants were analyzed. Among the HIV-infected and HIV-uninfected
      participants, a significant association was observed between age and cIMT [r =
      0.51, P < 0.0001 (HIV), r = 0.39, P < 0.0001, (non-HIV)], and between smoking
      burden and cIMT [r = 0.42, P < 0.0001 (HIV), r = 0.24, P = 0.003 (non-HIV)]. In
      multivariate regression modeling among all participants (HIV and non-HIV), a
      significant three-way interaction was observed between age, smoking burden, and
      HIV status with respect to cIMT (P < 0.010), controlling for sex, race, and
      traditional cardiovascular disease (CVD) risk factors, such that increased cIMT
      was associated with increased smoking burden and age to a greater degree among
      HIV-infected vs. HIV-uninfected participants. Among HIV-infected participants a
      significant interaction between smoking burden and age with respect to cIMT was
      seen (P = 0.027) controlling for race, sex, CVD risk factors, immunological
      function, and antiretroviral therapy use. CONCLUSION: A significant interaction
      between HIV, age, and smoking on cIMT was observed, suggesting that HIV-infection
      modifies the relationship of age and smoking on cIMT in this population. These
      findings emphasize the need to encourage smoking cessation in this population,
      due to its deleterious effect on subclinical atherosclerosis in older HIV
      infected patients.

PMID- 22874519
TI  - Identification of HIV-1-specific regulatory T-cells using HLA class II tetramers.
AB  - Regulatory T cells (Tregs) are potent immune modulators, but their precise role
      in HIV pathogenesis remains incompletely understood. Most studies to date have
      focused on frequencies or phenotypes of 'bulk' Treg populations. However,
      although antigen-specific Tregs have been reported in other diseases, HIV-1
      epitope-specific Tregs have not been described to date. We here report the first
      identification of functional HIV-1-Gag-specific regulatory T cells using human
      leukocyte antigen class II tetramer staining in HIV-1-infected individuals.

PMID- 22874520
TI  - Reduced diastolic function and left ventricular mass in HIV-negative
      preadolescent children exposed to antiretroviral therapy in utero.
AB  - OBJECTIVE: Abnormalities in left ventricular morphology and function have been
      reported in HIV-negative infants exposed to antiretroviral therapy (ART) in utero
      that persists throughout preschool age. The objective of this study was to
      determine if these abnormalities persist, resolve, or worsen during
      preadolescence. DESIGN: Cross-sectional observation study. METHODS: Thirty HIV
      negative children born to HIV-positive women and exposed to ART in utero (mean
      age 8 +/- 2 years, 37% female, 74% African-American) and 30 HIV-negative children
      born to HIV-negative women (mean age 8 +/- 3 years, 37% female, 76% African
      American) underwent two-dimensional Doppler, tissue Doppler, and strain
      echocardiography to evaluate left ventricular systolic and diastolic function.
      RESULTS: Weight, body surface area, heart rate and blood pressure were similar
      between groups. For the ART-exposed group, left ventricular mass index was lower
      (60 +/- 9 vs. 67 +/- 12 g/m, P < 0.02) and early diastolic annular velocity was
      lower (15.0 +/- 2.2 vs. 16.3 +/- 2.5 cm/s, P < 0.03) compared to controls. Left
      ventricular systolic function did not differ between groups. Lower maternal third
      trimester CD4 count was associated with lower early diastolic annular velocity;
      other non-HIV-related variables including cocaine use and increased maternal age
      correlated with lower left ventricular mass index. CONCLUSIONS: Abnormalities in
      left ventricular systolic performance previously reported in HIV-negative infants
      and preschool aged children exposed to ART in utero were not apparent in
      preadolescent children. Left ventricular diastolic relaxation was reduced
      compared with controls suggesting residual effects of ART exposure on left
      ventricular diastolic function. Larger, longitudinal studies are necessary to
      confirm these observations.

PMID- 22874521
TI  - Polyclonal serum-free light chains elevation in HIV-infected patients.
AB  - We investigated the association between polyclonal serum-free light chains and
      prognostic biomarkers routinely used in the setting of HIV infection. For this
      purpose serum samples of 182 HIV-infected patients from the Italian Cohort of
      Antiretroviral Naive Patients foundation cohort were analysed. We found that
      polyclonal serum free light chains above the upper normal limit are strongly
      correlated in HIV-infected patients with advancing age, shorter time of
      undetectable HIV viremia, higher viral load and with lower CD4 cell count at
      sample.

PMID- 22874523
TI  - Differences in medical care usage between two mass-gathering sporting events.
AB  - BACKGROUND: Event planning for mass gatherings involves the utilization of
      methods that prospectively can predict medical resource use. However, there is
      growing recognition that historical data for a specific event can help to
      accurately forecast medical requirements. This study was designed to investigate
      the differences in medical usage rates between two popular mass-gathering sports
      events in the UK: rugby matches and horse races. METHODS: A retrospective study
      of all attendee consultations with the on-site medical teams at the Leicester
      Tigers Rugby Football Club and the Leicester Racecourse from September 2008
      through August 2009 was undertaken. Patient demographics, medical usage rates,
      level of care, as well as professional input and the effects of alcohol use were
      recorded. RESULTS: Medical usage rates were higher at the Leicester Racecourse (P
      < .01), although the demographics of the patients were similar and included 24%
      children and 16% staff. There was no difference in level of care required between
      the two venues with the majority of cases being minor, although a higher
      proportion of casualties at the Leicester Tigers event were seen by a health care
      professional compared with the Leicester Racecourse (P < .001). Alcohol was a
      contributing factor in only 5% of consultations. CONCLUSIONS: These two major
      sporting venues had similar attendance requirements for medical treatment that
      are comparable to other mass-gathering sports events. High levels of staff and
      pediatric presentations may have an impact on human resource planning for events
      on a larger scale, and the separation of treatment areas may help to minimize the
      number of unnecessary or opportunistic reviews by the on-site health care
      professionals.

PMID- 22874522
TI  - Human papillomavirus infection and increased risk of HIV acquisition. A
      systematic review and meta-analysis.
AB  - OBJECTIVES: Human papillomavirus (HPV), one of the commonest sexually transmitted
      infections, may be a cofactor in HIV acquisition. We systematically reviewed the
      evidence for an association of HPV infection with HIV acquisition in women,
      heterosexual men and men who have sex with men (MSM). DESIGN: : Systematic review
      and meta-analysis. METHODS: Studies meeting inclusion criteria in Pubmed, Embase
      and conference abstracts up to 29 July 2011 were identified. Random effects meta
      analyses were performed to calculate summary hazard ratios (HR). Publication bias
      and statistical heterogeneity were evaluated and population attributable
      fractions (PAFs) calculated. RESULTS: Eight articles were included, with
      previously unpublished data from five authors. Seven studies found an association
      between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women
      doubled with prevalent HPV infection with any genotype [HR = 2.06 (95% CI = 1.44
      2.94), I = 0%], although adjustment for confounders was often inadequate. The
      effect was similar for high-risk [HR = 1.99 (95% CI = 1.54-2.56), I = 8.4%] and
      low-risk [HR = 2.01 (95% CI = 1.27-3.20), I = 0%] HPV genotypes with weak
      evidence of publication bias (P = 0.06). Two studies in men were identified: both
      showed an association between HPV infection and HIV acquisition. Unpublished data
      from one of two studies in women indicated an association between genotypes
      targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to
      infection with any HPV genotype ranged between 21 and 37%. CONCLUSION: If further
      studies validate the association between HPV infection and HIV acquisition, HPV
      vaccines may reduce HIV incidence in high HPV prevalence populations, in addition
      to preventing cervical cancer. HIV surveillance studies during implementation of
      HPV vaccine programmes are warranted.

PMID- 22874525
TI  - Cartilage and bone markers and inflammatory cytokines are increased in synovial
      fluid in the acute phase of knee injury (hemarthrosis)--a cross-sectional
      analysis.
AB  - PURPOSE: The aim of this cross-sectional study was to investigate concentrations
      of cartilage and bone markers, and pro-inflammatory cytokines in synovial fluid
      (SF) collected at different time-points from acutely injured knees with
      hemarthrosis and to compare these with SF concentrations of knees of age and
      gender-matched healthy reference subjects. METHODS: SF was aspirated from the
      acutely injured knee of 111 individuals (mean age 27 years, span 13-64 years, 22%
      women). Concentrations of sulfated glycosaminoglycan (sGAG) were measured by
      Alcian blue precipitation whereas cartilage ARGS, bone biomarkers [osteocalcin
      (OCL), secreted protein acidic and rich in cysteine (SPARC) and osteopontin
      (OPN)] and pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8 and
      tumor necrosis factor (TNF)-alpha] were analyzed using electrochemiluminescence.
      Samples were also analyzed with regard to time between injury and aspiration
      [same day (n = 29), 1 day (n = 31), 2-3 days (n = 19), 4-7 days (n = 20) and 8-23
      days (n = 12)]. RESULTS: SF concentrations of ARGS (P < 0.001), SPARC (P <
      0.001), OPN (P < 0.001), and all cytokines (P < 0.001), but not sGAG (P = 0.06)
      or OCL (P = 0.992), were significantly higher in injured knees compared to knees
      of reference subjects. The cartilage markers sGAG and ARGS were significantly
      higher in knees aspirated later than 1 day after injury, whereas concentrations
      of SPARC and OPN and all cytokines were higher in knees aspirated the same day as
      the injury and at all time-points thereafter. CONCLUSIONS: Our results suggest
      that an acute knee injury is associated with an instant local biochemical
      response to the trauma, which may affect cartilage and bone as well as the
      inflammatory activity.

PMID- 22874524
TI  - Knee malalignment is associated with an increased risk for incident and enlarging
      bone marrow lesions in the more loaded compartments: the MOST study.
AB  - OBJECTIVE: To examine the relationship of knee malalignment with occurrence of
      incident and enlarging bone marrow lesions (BMLs) and regression of BMLs.
      METHODS: Subjects from the Multicenter Osteoarthritis Study aged 50-79 years with
      or at high risk of knee osteoarthritis were studied. Full-limb radiographs were
      taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and
      30-month magnetic resonance imaging (MRI) of knees (n = 1782) were
      semiquantitatively assessed for BMLs. Outcome was defined as a change in BML
      score in femoral/tibial condyle in medial/lateral compartments. Medial
      compartment in varus alignment and lateral compartment in valgus alignment were
      combined to form 'more loaded' compartment, while lateral compartment in valgus
      and medial compartment in varus were combined to form 'less loaded' compartment.
      Relative risk (RR) of BML score increase or decrease in relation to malalignment
      was estimated using a log linear regression model with the Poisson assumption,
      adjusting for age, gender, body mass index, physical activity scale for the
      elderly, race and clinic site. Further, results were stratified by ipsilateral
      meniscal and cartilage status at baseline. RESULTS: Baseline varus alignment was
      associated with higher risk of BML score increase from baseline to follow-up in
      the medial compartment [adjusted RRs (95%CI): 1.5 (1.2-1.9)] and valgus alignment
      in the lateral compartment [1.4 (1.0-2.1)]. Increase in BML score was more likely
      in the more loaded compartments [1.7 (1.4-2.0)] in malaligned knees. Regardless
      of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase
      was higher in the more loaded compartments of malaligned knees than those with
      neutral alignment. Decrease in BML score was less likely in the more loaded
      compartments in malaligned knees [0.8 (0.7-1.0)]. CONCLUSION: Knee malalignment
      is associated with increased risk of incident and enlarging BMLs in the more
      loaded compartments of the tibiofemoral joint.

PMID- 22874526
TI  - Can breast cancer patients use soyafoods to help reduce risk of CHD?
AB  - Over the past 20 years, the popularity of soyafoods has increased in part because
      of research suggesting that these foods convey health benefits independent of
      their nutrient content. For example, in 1999, the US Food and Drug Administration
      approved a health-claim for soyafoods and CHD based on the hypocholesterolaemic
      effects of soya protein. However, soyafoods have become controversial in recent
      years because of concerns that their uniquely rich phyto-oestrogen (isoflavone)
      content may cause untoward effects in some individuals. Most notable in this
      regard is the concern that soyafoods are contraindicated for breast cancer
      patients and women at high risk of developing this disease. Furthermore, the
      hypocholesterolaemic effects of soya protein have been challenged. However, the
      results of recently published meta-analyses indicate that soya protein directly
      lowers circulating LDL-cholesterol levels by approximately 4 %. There is also
      intriguing evidence that soyafoods reduce CHD risk independent of their effects
      on lipid levels. In regard to the breast cancer controversy, recently published
      clinical and epidemiological data do not support observations in rodents that
      soyabean isoflavones increase breast cancer risk. In postmenopausal women,
      isoflavone exposure does not adversely affect breast tissue density or breast
      cell proliferation. Furthermore, both US and Chinese prospective epidemiological
      studies show that post-diagnosis soya consumption is associated with an improved
      prognosis. Therefore, soyafoods should be considered by women as healthy foods to
      include in diets aimed at reducing the risk of CHD regardless of their breast
      cancer status.

PMID- 22874527
TI  - Opisthorchis viverrini and Haplorchis taichui: development of a multiplex PCR
      assay for their detection and differentiation using specific primers derived from
      HAT-RAPD.
AB  - Specific primers for the detection of Opisthorchis viverrini and Haplorchis
      taichui were investigated by using the HAT-RAPD PCR method. Fourteen arbitrary
      primers (Operon Technologies) were performed for the generation of polymorphic
      DNA profiles. The results showed that a 319 bp fragment generated from the OPA-04
      primer was expected to be O. viverrini-specific while a 256 bp fragment generated
      from the OPP-11 primer was considered to be H. taichui-specific. Based on each
      sequence data, two pairs of specific primers were designed and sequences of each
      primer were as follows; H. taichui; Hapt_F5'-GGCCAACGCAATCGTCATCC-3'and Hapt_R1
      5'-CTCTCGACCTCCTCTAGAAT-3' which yielded a 170 bp PCR product. For O. viverrini,
      OpV-1F: 5'-AATCGGGCTGCATATTGACCGAT-3' and OpV-1R: 5'-CGGTGTTGCTTATTTTGCAGACAA-3'
      which generated a 319 bp PCR product. These specific primers were tested for
      efficacy and specific detection for all parasites DNA samples. The results showed
      that 170 and 319 bp specific PCR products were generated as equivalent to
      positive result in H. taichui and O. viverrini, respectively by having no cross
      reaction with any parasites tested. PCR conditions are recommended at 68 degrees
      C annealing temperature and with 0.5 mM magnesium chloride (Mg Cl(2)).
      Additionally, specific primers developed in this study were effective to
      determine the presence of both parasites in fish and snail intermediate hosts,
      which the DNA of O. viverrini was artificially spiked since it is rarely found in
      northern Thailand. The H. taichui and O. viverrini-specific primers successfully
      developed in this study can be use for epidemiological monitoring, preventing
      management and control programs.

PMID- 22874528
TI  - Do cerebral white matter lesions influence the rate of progression from mild
      cognitive impairment to dementia?
AB  - BACKGROUND: Cerebral white matter lesions (WML), evident on CT and MRI brain
      scans, are histopathologically heterogeneous but associated with vascular risk
      factors and thought mainly to indicate ischemic damage. There has been
      disagreement over their clinical prognostic value in predicting conversion from
      mild cognitive impairment (MCI) to dementia. METHODS: We scrutinised and rated CT
      and MRI brain scans for degree of WML in a memory clinic cohort of 129 patients
      with at least 1 year of follow-up. We examined the relationship between WML
      severity and time until conversion to dementia for all MCI patients and for
      amnestic (aMCI) and non-amnestic (naMCI) subgroups separately. RESULTS: Five-year
      outcome data were available for 87 (67%) of the 129 patients. The proportion of
      patients converting to dementia was 25% at 1 year and 76% at 5 years. Patients
      with aMCI converted to dementia significantly earlier than those with naMCI. WML
      severity was not associated with time to conversion to dementia for either MCI
      patients in general or aMCI patients in particular. Among naMCI patients, there
      was a tendency for those with a low degree of WML to survive without dementia for
      longer than those with a high degree of WML. However, this was not statistically
      significant. CONCLUSIONS: MCI subtype is a significant independent predictor of
      conversion to dementia, with aMCI patients having higher risk than naMCI for
      conversion throughout the 5-year follow-up period. WML severity does not
      influence conversion to dementia for aMCI but might accelerate progression in
      naMCI.

PMID- 22874529
TI  - Role of ESSENCE for preschool children with neurodevelopmental disorders.
AB  - Early Symptomatic Syndromes Eliciting Neurodevelopmental Examinations (ESSENCE)
      has been proposed as a guide to the neurodevelopmental needs of the under 5s. The
      problems are their multiplicity, the presence of partial features of specific
      conditions e.g. autism spectrum disorder and attention deficit/hyperactivity
      disorder and the young age of the children. For these reasons, child development
      teams often leave families to cope with very difficult situations. This paper
      includes epilepsy and the cerebral palsies to see if providing precise diagnostic
      categories and therapeutic targets can be achieved. It includes a discussion of
      causal sequences which have yet to be applied comprehensively to the
      neurodevelopment disorders.

PMID- 22874530
TI  - Cirsoid aneurysm of the right pre-auricular region: an unusual cause of tinnitus
      managed by endovascular glue embolisation.
AB  - OBJECTIVE: We report an interesting case of a right temporal pre-auricular
      arteriovenous fistula (cirsoid aneurysm) causing intractable tinnitus
      successfully managed by transarterial n-butyl cyanoacrylate glue embolisation.
      CASE REPORT: A 52-year-old female presented with a one-year history of tinnitus
      and pulsatile swelling in the right pre-auricular region. A colour Doppler
      ultrasound test and magnetic resonance angiography revealed a high-flow scalp
      arteriovenous fistula with a feeder vessel from the distal superficial temporal
      artery, which drained into the corresponding, dilated, tortuous vein. The patient
      underwent diagnostic digital subtraction angiography. This was followed by
      transarterial embolisation of the fistula using a 50 per cent mixture of n-butyl
      cyanoacrylate glue and Lipiodol(r), with manual distal venous occlusion. A
      successful outcome was achieved with instant relief of symptoms. CONCLUSION:
      Cirsoid aneurysms of the facial region, an uncommon cause of tinnitus, can be
      effectively managed by endovascular embolisation. This treatment obviates the
      need for surgery, which is associated with an increased risk of complications
      such as scarring, deformity and bleeding.

PMID- 22874532
TI  - The physician's role in physician-assisted suicide.

PMID- 22874533
TI  - Proposal for a Breakfast Quality Index (BQI) for children and adolescents.
AB  - OBJECTIVE: To propose and apply an instrument to assess the breakfast quality of
      children and adolescents in the Mediterranean area. DESIGN: Randomized, cross
      sectional survey of breakfast consumption using a validated semi-quantitative FFQ
      administered at school by trained dietitians between Tuesday and Friday. A
      Breakfast Quality Index (BQI) score was developed, assigning a positive value to
      the consumption of cereals, fruit, vegetables, dairy products, MUFA, Ca and
      compliance with energy recommendations, and to the absence of SFA and trans-rich
      fats. Data were analysed by Student's t test and ANOVA. SETTING: Schools in
      Granada and Balearic Islands (Spain). SUBJECTS: All schoolchildren (n 4332) aged
      8-17 years at randomly selected and representative schools between 2006 and 2008,
      stratified by age and sex. RESULTS: Breakfast was not consumed by 6.5 % of
      participants. BQI score was highest for children aged 7-9 years and decreased
      with age (P = 0.001). Females scored higher in all age groups. The lowest score
      was in males aged 14-17 years and the highest in females aged 7-9 years (P =
      0.006). CONCLUSIONS: The proposed BQI appears useful to estimate the breakfast
      quality of schoolchildren and to form a basis for nutrition education.

PMID- 22874531
TI  - Metabolic reprogramming of cancer-associated fibroblasts by TGF-beta drives tumor
      growth: connecting TGF-beta signaling with "Warburg-like" cancer metabolism and L
      lactate production.
AB  - We have previously shown that a loss of stromal Cav-1 is a biomarker of poor
      prognosis in breast cancers. Mechanistically, a loss of Cav-1 induces the
      metabolic reprogramming of stromal cells, with increased autophagy/mitophagy,
      mitochondrial dysfunction and aerobic glycolysis. As a consequence, Cav-1-low
      CAFs generate nutrients (such as L-lactate) and chemical building blocks that
      fuel mitochondrial metabolism and the anabolic growth of adjacent breast cancer
      cells. It is also known that a loss of Cav-1 is associated with hyperactive TGF
      beta signaling. However, it remains unknown whether hyperactivation of the TGF
      beta signaling pathway contributes to the metabolic reprogramming of Cav-1-low
      CAFs. To address these issues, we overexpressed TGF-beta ligands and the TGF-beta
      receptor I (TGFbeta-RI) in stromal fibroblasts and breast cancer cells. Here, we
      show that the role of TGF-beta in tumorigenesis is compartment-specific, and that
      TGF-beta promotes tumorigenesis by shifting cancer-associated fibroblasts toward
      catabolic metabolism. Importantly, the tumor-promoting effects of TGF-beta are
      independent of the cell type generating TGF-beta. Thus, stromal-derived TGF-beta
      activates signaling in stromal cells in an autocrine fashion, leading to
      fibroblast activation, as judged by increased expression of myofibroblast
      markers, and metabolic reprogramming, with a shift toward catabolic metabolism
      and oxidative stress. We also show that TGF-beta-activated fibroblasts promote
      the mitochondrial activity of adjacent cancer cells, and in a xenograft model,
      enhancing the growth of breast cancer cells, independently of angiogenesis.
      Conversely, activation of the TGF-beta pathway in cancer cells does not influence
      tumor growth, but cancer cell-derived-TGF-beta ligands affect stromal cells in a
      paracrine fashion, leading to fibroblast activation and enhanced tumor growth. In
      conclusion, ligand-dependent or cell-autonomous activation of the TGF-beta
      pathway in stromal cells induces their metabolic reprogramming, with increased
      oxidative stress, autophagy/mitophagy and glycolysis, and downregulation of Cav
      1. These metabolic alterations can spread among neighboring fibroblasts and
      greatly sustain the growth of breast cancer cells. Our data provide novel
      insights into the role of the TGF-beta pathway in breast tumorigenesis, and
      establish a clear causative link between the tumor-promoting effects of TGF-beta
      signaling and the metabolic reprogramming of the tumor microenvironment.

PMID- 22874534
TI  - Cardiorespiratory fitness, alcohol intake, and metabolic syndrome incidence in
      men.
AB  - PURPOSE: The objective of this study is to prospectively examine the independent
      and joint effects of alcohol consumption and cardiorespiratory fitness on the
      incidence of metabolic syndrome (MetS) in a cohort of men. METHODS: A prospective
      examination was done of 3411 apparently healthy men at baseline, who came to the
      Cooper Clinic (Dallas, TX) for at least two preventive visits (1979-2010).
      Primary exposure variables were cardiorespiratory fitness and alcohol intake; the
      outcome measure was MetS and the components thereof. Cox proportional hazards
      models were computed to assess the relation between the exposure variables and
      the incidence of MetS while adjusting for confounders. RESULTS: For a mean follow
      up period of 9 yr (SD = 7.8), 276 men developed MetS. In multivariable analysis,
      a dose-response relationship was observed between increased levels of fitness and
      reduced MetS risk (moderate fitness: HR = 0.60; 95% confidence interval (CI),
      0.43-0.82; high fitness: HR = 0.49, 95% CI, 0.35-0.69). When examining the
      independent effects of alcohol, light drinking increased the risk for MetS by 66%
      (HR = 1.66, 95% CI, 1.11-2.48). No statistically significant interaction effect
      was observed between alcohol and fitness in relation to MetS (P = 0.32). When
      assessing the relation between each exposure and the components of MetS, higher
      fitness consistently reduced the risk of all components, whereas lower alcohol
      intake reduced the risk of elevated glucose and blood pressure and increased the
      risk for low HDL cholesterol. CONCLUSIONS: Among this cohort of men, higher
      fitness levels reduced the risk for MetS and its components. The relation between
      alcohol intake levels and metabolic risk was more complex and not reflected when
      examining MetS as a whole.

PMID- 22874535
TI  - Dietary nitrate does not enhance running performance in elite cross-country
      skiers.
AB  - PURPOSE: The objective of this study is to examine the effects of acute ingestion
      of dietary nitrate on endurance running performance in highly trained cross
      country skiers. Dietary nitrate has been shown to reduce the oxygen cost of
      submaximal exercise and improve tolerance of high-intensity exercise, but it is
      not known if this holds true for highly trained endurance athletes. METHODS: Ten
      male junior cross-country skiers (VO(2max)) ~ 70 mL.kg.min) each completed two
      trials in a randomized, double-blind design. Participants ingested potassium
      nitrate (614-mg nitrate) or a nitrate-free placebo 2.5 h before two 5-min
      submaximal tests on a treadmill at 10 km.h (~55% of VO(2max)) and 14 km.h (~75%
      of VO(2max)), followed by a 5-km running time trial on an indoor track. RESULTS:
      Plasma nitrite concentrations were higher after nitrate supplementation (325 +/-
      95 nmol.L) compared with placebo (143 +/- 59 nmol.L, P < 0.001). There was no
      significant difference in 5-km time-trial performance between nitrate (1005 +/-
      53 s) and placebo treatments (996 +/- 49 s, P = 0.12). The oxygen cost of
      submaximal running was not significantly different between placebo and nitrate
      trials at 10 km.h (both 2.84 +/- 0.34 L.min) and 14 km.h (3.89 +/- 0.39 vs. 3.77
      +/- 0.62 L.min). CONCLUSIONS: Acute ingestion of dietary nitrate may not
      represent an effective strategy for reducing the oxygen cost of submaximal
      exercise or for enhancing endurance exercise performance in highly trained cross
      country skiers.

PMID- 22874536
TI  - Resistance training reduces subclinical inflammation in obese, postmenopausal
      women.
AB  - PURPOSE: Aerobic exercise is frequently prescribed to reduce inflammatory-related
      disease (cardiovascular disease and diabetes) risk. Resistance training (RT),
      however, may be key to maximizing anti-inflammatory benefits of consistent
      exercise. We examined the influence of RT on inflammatory biomarkers in obese,
      postmenopausal women. METHODS: Twenty-three women (65.6 +/- 2.6 yr; body mass
      index, 33 kg.m) underwent 12 wk of RT (3 sets, 10 exercises, 3* per week, 8-12
      repetition maximum (RM), resistance exercise (EX), N = 11) or social interaction
      intervention (SI, stretching, knitting, health lectures, 2* per week, control
      group (CON), N = 12). Both before (BT) and after (AT) RT or SI, blood was
      collected before (PR), immediately (PO), 2 h (2H), and 24 h (24H) after a single
      resistance exercise bout (RE) in EX and at the same time points in nonexercise,
      resting CON. For all time points, blood was analyzed for IL-6, leptin, and
      lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) (LPS
      TNF) and IL-10 (LPS-IL10). PR samples were also examined for C-reactive protein,
      TNF-alpha, and adiponectin, and mRNA expression of toll-like receptor 4 (TLR4)
      and MC1R. Subcutaneous adipose tissue was extracted BT and AT and analyzed for
      mRNA expression of monocyte chemotactic protein-1, leptin, CD68, and TLR4.
      RESULTS: RT improved strength (44%) and reduced circulating C-reactive protein (
      33%), leptin (-18%) and TNF-alpha (-29%) with no change in body composition. IL-6
      decreased after SI in CON (-17%). LPS-TNF increased after SI or RT (CON +26%, EX
      +67%, respectively), whereas LPS-IL10 decreased in CON (-28%) but increased in EX
      (+20%). RT did not influence inflammatory biomarker gene expression in whole
      blood or subcutaneous adipose tissue. A single RE bout augmented LPS-TNF and LPS
      IL10 at 24H in EX, particularly AT. CONCLUSION: RT reduced markers of subclinical
      inflammation in circulation in obese, postmenopausal women in the absence of
      changes in body composition. Chronic RT also enhanced response to endotoxin
      challenge both at rest (PR) and 24 h after an acute RE bout (24H).

PMID- 22874537
TI  - Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation
      resulting in increased repression of VEGF signalling genes.
AB  - The PRH/Hhex transcription factor represses multiple genes in the VEGF signalling
      pathway (VSP) to inhibit myeloid cell survival. Protein kinase CK2 phosphorylates
      PRH and counteracts the inhibitory effect of this protein on cell survival by
      blocking the repression of VSP genes. Here we show that the BCR-ABL/Src kinase
      inhibitor dasatinib decreases PRH phosphorylation and increases PRH-dependent
      repression of Vegf and Vegfr-1. Moreover in the absence of PRH, dasatinib does
      not inhibit cell survival as effectively as in PRH expressing cells. Thus the re
      establishment of gene control by PRH is in part responsible for the therapeutic
      effects of dasatinib.

PMID- 22874538
TI  - Adherence to a healthy Nordic food index is associated with a lower incidence of
      colorectal cancer in women: the Diet, Cancer and Health cohort study.
AB  - Colorectal cancer (CRC) is a multi-factorial disease in which diet is believed to
      play a role. Little is known about the health effects of specific regional diets.
      The Nordic diet is high in fat and sugar but also includes a range of traditional
      products with anticipated health-promoting effects. The aim of this cohort study
      was to determine whether a healthy Nordic food index consisting of fish, cabbage,
      rye bread, oatmeal, apples, pears and root vegetables was related to CRC
      incidence. Data were obtained from a prospective cohort study of 57,053 Danish
      men and women aged 50-64 years, of whom 1025 developed CRC (13 years' follow-up).
      Incidence rate ratios (IRR) with 95 % CI were calculated from Cox proportional
      hazard models. Women who strongly adhered to a healthy Nordic food index had a 35
      % lower incidence of CRC than women with poor adherence (adjusted IRR, 0.65; 95 %
      CI 0.46, 0.94); a similar tendency was found for men. Women had a 9 % lower
      incidence of CRC per point adherence to the healthy Nordic food index, but no
      significant effect was found for men. A regional diet based on healthy Nordic
      food items was therefore associated with a lower incidence of CRC in women. The
      protective effect was of the same magnitude as previously found for the
      Mediterranean diet, suggesting that healthy regional diets should be promoted in
      order to ensure health; this will also preserve cultural heredity and the
      environment.

PMID- 22874539
TI  - Early enteral nutrition in critically ill patients.
AB  - Malnutrition in the critically ill patient is associated with adverse outcomes
      such as increased morbidity, infectious processes, and length of stay.
      Alterations to the gastrointestinal system during critical illness can be
      devastating. Current evidence suggests that, in the presence of a functioning
      gut, initiating early enteral nutrition therapy (within 24-48 hours of intensive
      care unit admission) results in enhanced tissue repair, preservation of immune
      competence, and conservation of the integrity of gut flora. Recommendations for
      practice include development of a national nutrition support protocol for
      widespread use in the intensive care unit.

PMID- 22874542
TI  - Communicating with the unresponsive patient: a student review.
AB  - Providing patient care for the unconscious population in the intensive care unit
      can be very challenging. Over time, some nurses may face barriers that prevent
      them from providing caring behaviors, such as communication. Review of the
      literature found the attitude of a nurse, hospital technology, and the working
      environment are barriers that prevent therapeutic nurse-patient communication
      with a patient who is unconscious or sedated and ventilated. Becoming more
      knowledgeable about how communication can help and what can be done if such
      barriers present themselves in the hospital setting is beneficial to improving
      nurses' care in the intensive care unit.

PMID- 22874543
TI  - Innovative solutions: the C.O.R.E. to sociocultural care in nursing.
AB  - Terminal weaning of patients follows a standardized medical care protocol.
      However, the evidence found for optimal terminal weaning protocols may lack
      individualization for the patient and family. As nursing students in the critical
      care unit, we have designed a conceptual model that bridges the gap between
      cultural diversity and terminal weaning. This conceptual model integrates
      comfort, organization, rituals, and environment into the process of terminal
      weaning. The model assists nurses in all specialties, particularly critical care,
      to provide culturally appropriate end-of-life care for the patient and their
      family.

PMID- 22874545
TI  - Personal reflection: death brokering for critical care nurses.
AB  - End-of-life care and the dying patient have been an area lightly covered in my
      nursing school experience. While I expected the topics to surface in more detail
      in conjunction with the critical care nursing unit, this was not the case. This
      article is a personal reflection on my experience in critical care nursing and
      the deficits involving death and dying education in both institutional and
      professional settings.

PMID- 22874546
TI  - Improving staff compliance with isolation precautions through use of an
      educational intervention and behavioral contract.
AB  - Hospital-acquired infections negatively impact patient outcomes, length of stay,
      and the economy. Health care systems must find ways to decrease the spread of
      infection and the development of infection with the use of isolation precautions
      in an acute care setting. All staff members must be aware of ways to decrease or
      prevent the spread of infection by the appropriate use of isolation precautions.
      This article describes a successful program that improved the use of isolation
      precautions among nursing personnel through the implementation of an educational
      intervention and behavioral contract.

PMID- 22874547
TI  - Performance anxiety in new graduate nurses: is it for real?
AB  - Every new nursing graduate is challenged to successfully transition from student
      to professional nurse. The stress involved in the transition can manifest as
      performance anxiety. This study was conducted to verify the presence and identify
      the level of performance anxiety in a sample of new graduate nurses. Results
      included a significant decrease in performance anxiety by the end of the 6-month
      study period.

PMID- 22874549
TI  - An evidence-based oral care protocol to decrease ventilator-associated pneumonia.
AB  - The purpose of this study was to examine the impact of 0.12% chlorhexidine rinses
      and an oral care protocol on ventilator-associated pneumonia rates. A quasi
      experimental preintervention-postintervention design was used. The sample
      included all patients admitted to critical care and on mechanical ventilation at
      any time during the study period. Data were collected 6 months before and 12
      months after intervention. Ventilator-associated pneumonia rates were reduced
      from 4.3 to 1.86 per 1000 ventilator-days during the study period, with an
      estimated cost avoidance of $700,000 to $798,000.

PMID- 22874553
TI  - ATG16L1 and pathogenesis of urinary tract infections.
AB  - Autophagy is generally considered to be antipathogenic. The autophagy gene
      ATG16L1 has a commonly occurring mutation associated with Crohn disease (CD) and
      intestinal cell abnormalities. Mice hypomorphic for ATG16L1 (ATG16L1(HM))
      recreate specific features of CD. Our recent study shows that the same
      ATG16L1(HM) mice that are susceptible to intestinal inflammatory disease are
      protected from urinary tract infections (UTI), a common and important human
      disease primarily caused by uropathogenic E. coli (UPEC). UPEC colonize the
      bladder and exhibit both luminal and intra-epithelial stages. The host responds
      by recruiting innate immune cells and shedding infected epithelial cells to clear
      infection. Despite these countermeasures, UPEC can persist within the bladder
      epithelium as membrane-enclosed quiescent intracellular reservoirs (QIRs) that
      can seed recurrent UTI. The mechanisms of persistence remain unknown. In this
      study, we show that ATG16L1 deficiency protects the host against acute UTI and
      UPEC latency. ATG16L1(HM) mice clear urinary bacterial loads more rapidly and
      thoroughly due to ATG16L1-deficient innate immune components. Furthermore,
      ATG16L1(HM) mice exhibit superficial urothelial cell-autonomous architectural
      aberrations that also result in significantly reduced QIR numbers. Our findings
      reveal a host-protective effect of ATG16L1 deficiency in vivo against a common
      pathogen.

PMID- 22874552
TI  - LAMP2A overexpression in breast tumors promotes cancer cell survival via
      chaperone-mediated autophagy.
AB  - Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the
      chaperone-mediated autophagy (CMA) pathway. LAMP2A helps in lysosomal uptake of
      modified and oxidatively damaged proteins directly into the lumen of lysosomes
      for degradation and protein turnover. Elevated expression of LAMP2A was observed
      in breast tumor tissues of all patients under investigation, suggesting a
      survival mechanism via CMA and LAMP2A. Reduced expression of the CMA substrates,
      GAPDH and PKM, was observed in most of the breast tumor tissues when compared
      with the normal adjacent tissues. Reactive oxygen species (ROS) mediated
      oxidative stress damages regulatory cellular components such as DNA, proteins
      and/or lipids. Protein carbonyl content (PCC) is widely used as a measure of
      total protein oxidation in cells. Ectopic expression of LAMP2A reduces PCC and
      thereby promotes cell survival during oxidative stress. Furthermore, inhibition
      of LAMP2A stimulates accumulation of GAPDH, AKT1 phosphorylation, generation of
      ROS, and induction of cellular apoptosis in breast cancer cells. Doxorubicin,
      which is a chemotherapeutic drug, often becomes ineffective against tumor cells
      with time due to chemotherapeutic resistance. Breast cancer cells deficient of
      LAMP2A demonstrate increased sensitivity to the drug. Thus, inhibiting CMA
      activity in breast tumor cells can be exploited as a potential therapeutic
      application in the treatment of breast cancer.

PMID- 22874554
TI  - Selective autophagy regulates T cell activation.
AB  - T cells are essential for defense of the host against invading pathogens. Antigen
      activation of the T cell receptor (TCR) is required for generation of an adaptive
      immune response. Several groups have observed that blocking autophagy augments T
      cell activation, but the molecular basis of this finding has remained elusive.
      The adaptor protein BCL10 transmits activating signals from the TCR to NFKB1
      RELA/NFkappaB, a transcription factor that is critical for T cell proliferation
      and function. We recently reported that a TCR-dependent autophagy mechanism
      selectively targets and degrades BCL10. We found that BCL10 autophagy requires
      BCL10 K63-polyubiquitination and subsequent binding to the autophagy adaptor
      SQSTM1/p62. Blocking either one of these processes inhibits BCL10 degradation.
      Protecting BCL10 from autophagic degradation, either by pharmacological or
      genetic inhibition of autophagy, results in increased activation of NFKB1-RELA.
      By demonstrating the mechanism of autophagic uptake and degradation of BCL10, our
      study has revealed a key mechanism by which selective autophagy controls T cell
      activation. Here, we discuss the implications of our findings and explore
      possible directions for future research.

PMID- 22874555
TI  - CD47 deficiency confers cell and tissue radioprotection by activation of
      autophagy.
AB  - Accidental or therapeutic exposure to ionizing radiation has severe physiological
      consequences and can result in cell death. We previously demonstrated that
      deficiency or blockade of the ubiquitously expressed receptor CD47 results in
      remarkable cell and tissue protection against ischemic and radiation stress.
      Antagonists of CD47 or its ligand THBS1/thrombospondin 1 enhance cell survival
      and preserve their proliferative capacity. However the signaling pathways that
      mediate this cell-autonomous radioprotection are unclear. We now report a marked
      increase in autophagy in irradiated T-cells and endothelial cells lacking CD47.
      Irradiated T cells lacking CD47 exhibit significant increases in formation of
      autophagosomes comprising double-membrane vesicles visualized by electron
      microscopy and numbers of MAP1LC3A/B(+) puncta. Moreover, we observed significant
      increases in BECN1, ATG5, ATG7 and a reduction in SQSTM1/p62 expression relative
      to irradiated wild-type T cells. We observed similar increases in autophagy gene
      expression in mice resulting from blockade of CD47 in combination with total body
      radiation. Pharmacological or siRNA-mediated inhibition of autophagy selectively
      sensitized CD47-deficient cells to radiation, indicating that enhanced autophagy
      is necessary for the prosurvival response to CD47 blockade. Moreover, re
      expression of CD47 in CD47-deficient T cells sensitized these cells to death by
      ionizing radiation and reversed the increase in autophagic flux associated with
      survival. This study indicates that CD47 deficiency confers cell survival through
      the activation of autophagic flux and identifies CD47 blockade as a
      pharmacological route to modulate autophagy for protecting tissue from radiation
      injury.

PMID- 22874556
TI  - Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of
      stroke.
AB  - Autophagy is an important cellular recycling mechanism through self-digestion in
      responses to cellular stress such as starvation. Studies have shown that
      autophagy is involved in maintaining the homeostasis of the neural system during
      stroke. However, molecular mechanisms underlying neuronal autophagy in ischemic
      stroke remain poorly understood. Previously, we and others have shown that immune
      related GTPase M (IRGM; termed IRGM1 in the mouse nomenclature) can regulate the
      survival of immune cells through autophagy in response to infections and
      autoimmune conditions. Here, using a permanent middle cerebral artery occlusion
      (pMCAO) mouse model, we found that IRGM1 was upregulated in the ischemic side of
      the brain, which was accompanied by a significant autophagic response. In
      contrast, neuronal autophagy was almost complete lost in Irgm1 knockout (KO) mice
      after pMCAO induction. In addition, the infarct volume in the Irgm1-KO pMCAO mice
      was significantly increased as compared to wild-type mice. Histological studies
      suggested that, at the early stage (within 24 h) of ischemia, the IRGM1-dependent
      autophagic response is associated with a protection of neurons from necrosis in
      the ischemic core but a promotion of neuronal apoptosis in the penumbra area.
      These data demonstrate a novel role of IRGM1 in regulating neuronal autophagy and
      survival during ischemic stroke.

PMID- 22874557
TI  - Autophagy on acid.
AB  - The microenvironment of solid tumors tends to be more acidic (6.5-7.0) than
      surrounding normal (7.2-7.4) tissue. Chaotic vasculature, oxygen limitation and
      major metabolic changes all contribute to the acidic microenvironment. We have
      previously proposed that low extracellular pH (pHe) plays a critical role in the
      development and progression of solid tumors. While extracellular acidosis is
      toxic to most normal cells, cancer cells can adapt and survive under this harsh
      condition. In this study, we focused on identifying survival strategies employed
      by cancer cells when challenged with an acidic pHe (6.6-6.7) either acutely or
      for many generations. While acutely acidic cells did not grow, those acclimated
      over many generations grew at the same rate as control cells. We observed that
      these cells induce autophagy in response to acidosis both acutely and
      chronically, and that this adaptation appears to be necessary for survival.
      Inhibition of autophagy in low pH cultured cells results in cell death.
      Histological analysis of tumor xenografts reveals a strong correlation of LC3
      protein expression in regions projected to be acidic. Furthermore, in vivo
      buffering experiments using sodium bicarbonate, previously shown to raise
      extracellular tumor pH, decreases LC3 protein expression in tumor xenografts.
      These data imply that autophagy can be induced by extracellular acidosis and
      appears to be chronically employed as a survival adaptation to acidic
      microenvironments.

PMID- 22874558
TI  - Stimulation of autophagy is neuroprotective in a mouse model of human tauopathy.
AB  - The most common neurodegenerative diseases are characterized by the accumulation
      of misfolded proteins. Tauopathies, which include Alzheimer disease, progressive
      supranuclear palsy, corticobasal degeneration, Pick disease and cases of
      frontotemporal dementia and parkinsonism linked to chromosome 17, are
      characterized by the accumulation of hyperphosphorylated and filamentous MAPT/tau
      protein. The pathological mechanisms involved in MAPT protein accumulation are
      not well understood, but a possible impairment of protein degradation pathways
      has been suggested. We investigated the effects of autophagy stimulation on MAPT
      pathology in a model tauopathy, the human mutant P301S MAPT transgenic mouse
      line. In the brain of the trehalose-treated mutant mice, autophagy is activated
      and a reduced number of neurons containing MAPT inclusions, as well as a
      decreased amount of insoluble MAPT, are observed. The improvement of MAPT
      pathology is associated with increased nerve cell survival. Moreover, MAPT
      inclusions colocalize with SQSTM1/p62- and LC3-positive puncta, suggesting the
      colocalization of MAPT aggregates with autophagic vacuoles. Autophagy is not
      activated in the spinal cord of the human P301S MAPT transgenic mice and neuronal
      survival, as well as MAPT pathology, is unaffected. This study supports a role
      for autophagy stimulation in the degradation of MAPT aggregates and opens new
      perspectives for the investigation of autophagy as a pathological mechanism
      involved in neurodegenerative diseases.

PMID- 22874559
TI  - CAV1/caveolin 1 enhances aerobic glycolysis in colon cancer cells via activation
      of SLC2A3/GLUT3 transcription.
AB  - Although elevated expression of CAV1/caveolin 1 is associated with the malignant
      progression of various human cancers, the molecular mechanism underlying its
      oncogenic functions is largely unknown. We found that CAV1 is frequently
      overexpressed in advanced colorectal tumors due to aberrant promoter CpG site
      hypomethylation, and its elevation is implicated in enhanced aerobic glycolysis
      of tumor cells. Depletion of elevated CAV1 downregulates glucose uptake,
      intracellular ATP level and lactate accumulation, and triggers autophagy through
      activation of AMPK-TP53/p53 signaling. CAV1 elevation increases glucose uptake
      and ATP production by stimulating transcription of the glucose transporter
      SLC2A3/GLUT3 via an HMGA1-binding site within the promoter. Collectively, our
      study suggests that elevated CAV1 expression may contribute to colorectal tumor
      progression by providing tumor cells growth and survival advantages under
      nutritional stress conditions.

PMID- 22874560
TI  - Recycling endosomes contribute to autophagosome formation.
AB  - Autophagosome formation is a complex cellular process, which requires major
      membrane rearrangements leading to the creation of a relatively large double
      membrane vesicle that directs its contents to the lysosome for degradation.
      Although various membrane compartments have been identified as sources for
      autophagosomal membranes, the molecular mechanism underlying these membrane
      trafficking steps remains elusive. To address this question we performed a
      systematic analysis testing all known Tre-2/Bub2/Cdc16 (TBC) domain-containing
      proteins for their ability to inhibit autophagosome formation by disrupting a
      specific membrane trafficking step. TBC proteins are thought to act as inhibitors
      of Rab GTPases, which regulate membrane trafficking events. Up to 11 TBC proteins
      inhibit autophagy when overexpressed and one of these, TBC1D14, acts at an early
      stage during autophagosome formation and is involved in regulating recycling
      endosomal traffic. We found that the early acting autophagy proteins ATG9 and
      ULK1 localize to transferrin receptor (TFR)-positive recycling endosomes (RE),
      which are tubulated by excess TBC1D14 leading to an inhibition of autophagosome
      formation. Finally, transferrin (TF)-containing recycling endosomal membranes can
      be incorporated into newly forming autophagosomes, although it is likely that
      most of the autophagosome membrane is subsequently acquired from other sources.

PMID- 22874561
TI  - Atg36: the Saccharomyces cerevisiae receptor for pexophagy.
AB  - Eukaryotic cells adapt their organelle composition and abundance according to
      environmental conditions. Analysis of the peroxisomal membrane protein Pex3 has
      revealed that this protein plays a crucial role in peroxisome maintenance as it
      is required for peroxisome formation, segregation and breakdown. Although its
      function in peroxisome formation and segregation was known to involve its
      recruitment to the peroxisomal membrane of factors specific for these processes,
      the role of Pex3 in peroxisome breakdown was unclear until our recent
      identification of Atg36 as a novel Saccharomyces cerevisiae Pex3-interacting
      protein. Atg36 is recruited to peroxisomes by Pex3 and is required specifically
      for pexophagy. Atg36 is distinct from Atg30, the pexophagy receptor identified in
      Pichia pastoris. Atg36 interacts with Atg11 in vivo, and to a lesser extent with
      Atg8. These latter proteins link autophagic cargo receptors to the core autophagy
      machinery. Like other autophagic cargo receptors, Atg36 is a suicide receptor and
      is broken down in the vacuole together with its cargo. Unlike other cargo
      receptors, the interaction between Atg36 and Atg8 does not seem to be direct. Our
      recent findings suggest that Atg36 is a novel pexophagy receptor that may target
      peroxisomes for degradation via a noncanonical mechanism.

PMID- 22874562
TI  - Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme
      inhibitor MLN4924 triggers protective autophagy in cancer cells.
AB  - The multiunit Cullin (CUL)-RING E3 ligase (CRL) controls diverse biological
      processes by targeting a mass of substrates for ubiquitination and degradation,
      whereas its dysfunction causes carcinogenesis. Post-translational neddylation of
      CUL, a process triggered by the NEDD8-activating enzyme E1 subunit 1 (NAE1), is
      required for CRL activation. Recently, MLN4924 was discovered via a high
      throughput screen as a specific NAE1 inhibitor and first-in-class anticancer
      drug. By blocking CUL neddylation, MLN4924 inactivates CRL and causes the
      accumulation of CRL substrates that trigger cell cycle arrest, senescence and/or
      apoptosis to suppress the growth of cancer cells in vitro and in vivo. Recently,
      we found that MLN4924 also triggers protective autophagy in response to CRL
      inactivation. MLN4924-induced autophagy is attributed partially to the inhibition
      of mechanistic target of rapamycin (also known as mammalian target of rapamycin,
      MTOR) activity by the accumulation of the MTOR inhibitory protein DEPTOR, as well
      as reactive oxygen species (ROS)-induced stress. Moreover, the blockage of
      autophagy response enhances apoptosis in MLN4924-treated cells. Together, our
      findings not only reveal autophagy as a novel cellular response to CRL
      inactivation by MLN4924, but also provide a piece of proof-of-concept evidence
      for the combination of MLN4924 with autophagy inhibitors to enhance therapeutic
      efficacy.

PMID- 22874565
TI  - DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by
      activating selective autophagy.
AB  - Metastasis is the spread of cancer cells from their primary location to other
      parts of the body. Metastatic cancer is responsible for most cancer deaths.
      Increasing evidence indicates that epithelial-mesenchymal transition (EMT), a
      crucial developmental program, contributes to control cancer invasion and
      metastasis. We recently reported that death effector domain-containing DNA
      binding protein (DEDD), a key effector molecule for cell death signaling
      receptors, attenuates EMT and acts as an endogenous suppressor of tumor growth
      and metastasis. We found that DEDD physically interacts with the class III PtdIns
      3-kinase complex containing PIK3C3 and BECN1, which controls critical aspects of
      autophagy; this interaction activates autophagy and induces the autophagy
      mediated lysosomal degradation of SNAI/Snail and TWIST, two master inducers of
      the EMT process. Further study reveals that the DEDD-PIK3C3 interaction can
      support the stability of PIK3C3 to maintain autophagic activity and promote the
      degradation of SNAI and TWIST. Our finding indicates that DEDD is a prognostic
      marker and a potential therapeutic target for the prevention and treatment of
      cancer metastasis. Moreover, regulation of the DEDD-PIK3C3 interaction may serve
      as an entry point to translate modifiers of this interaction into clinical
      endpoints.

PMID- 22874563
TI  - Targeting autophagy as a novel strategy for facilitating the therapeutic action
      of potentiators on DeltaF508 cystic fibrosis transmembrane conductance regulator.
AB  - Channel activators (potentiators) of cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR), can be used for the treatment of the small subset
      of CF patients that carry plasma membrane-resident CFTR mutants. However,
      approximately 90% of CF patients carry the misfolded DeltaF508-CFTR and are
      poorly responsive to potentiators, because DeltaF508-CFTR is intrinsically
      unstable at the plasma membrane (PM) even if rescued by pharmacological
      correctors. We have demonstrated that human and mouse CF airways are autophagy
      deficient due to functional sequestration of BECN1 and that the tissue
      transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent
      autophagy and reduce SQSTM1/p62 levels, thus favoring DeltaF508-CFTR trafficking
      to the epithelial surface. Here, we investigated whether these treatments could
      facilitate the beneficial action of potentiators on DeltaF508-CFTR homozygous
      airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134
      stabilized DeltaF508-CFTR at the plasma membrane of airway epithelial cells and
      sustained the expression of CFTR at the epithelial surface well beyond drug
      withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the
      beneficial action of potentiators in controlling inflammation in ex vivo
      DeltaF508-CFTR homozygous human nasal biopsies and in vivo in mouse DeltaF508
      CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in DeltaF508-CFTR mice
      synergized with potentiators in sustaining surface CFTR expression and
      suppressing inflammation. Cystamine pre-treatment restored DeltaF508-CFTR
      response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly
      isolated brushed nasal epithelial cells from DeltaF508-CFTR homozygous patients.
      These findings delineate a novel therapeutic strategy for the treatment of CF
      patients with the DeltaF508-CFTR mutation in which patients are first treated
      with cystamine and subsequently pulsed with CFTR potentiators.

PMID- 22874564
TI  - Activation of the macroautophagic system in scrapie-infected experimental animals
      and human genetic prion diseases.
AB  - Macroautophagy is an important process for removing misfolded and aggregated
      protein in cells, the dysfunction of which has been directly linked to an
      increasing number of neurodegenerative disorders. However, the details of
      macroautophagy in prion diseases remain obscure. Here we demonstrated that in the
      terminal stages of scrapie strain 263K-infected hamsters and human genetic prion
      diseases, the microtubule-associated protein 1 light chain 3 (LC3) was converted
      from the cytosolic form to the autophagosome-bound membrane form. Macroautophagy
      substrate sequestosome 1 (SQSTM1) and polyubiquitinated proteins were
      downregulated in the brains of sick individuals, indicating enhanced
      macroautophagic protein degradation. The levels of mechanistic target of
      rapamycin (MTOR) and phosphorylated MTOR (p-MTOR) were significantly decreased,
      which implies that this enhancement of the macroautophagic response is likely
      through the MTOR pathway which is a negative regulator for the initiation of
      macroautophagy. Dynamic assays of the autophagic system in the brains of scrapie
      experimental hamsters after inoculation showed that alterations of the autophagic
      system appeared along with the deposits of PrP(Sc) in the infected brains.
      Immunofluorescent assays revealed specific staining of autophagosomes in neurons
      that were not colocalized with deposits of PrP(Sc) in the brains of scrapie
      infected hamsters, however, autophagosome did colocalize with PrP(Sc) in a prion
      infected cell line after treatment with bafilomycin A(1). These results suggest
      that activation of macroautophagy in brains is a disease-correlative phenomenon
      in prion diseases.

PMID- 22874566
TI  - IFNG and autophagy: a critical role for the ER-stress mediator ATF6 in
      controlling bacterial infections.
AB  - IFNG/IFNgamma plays a critical role in driving innate and acquired defenses
      against infectious pathogens. The death-associated protein kinase 1 (DAPK1),
      originally identified as an activator of IFNG-induced cell death, controls
      autophagy. Previously, we have shown that transcription factor CEBPB (C/EBP-beta)
      regulates IFNG-induced expression of Dapk1 through a CRE/ATF motif in its
      enhancer. In this paper we have shown that ATF6, an ER-resident transcription
      factor regulates IFNG-induced Dapk1 expression through the CRE/ATF site, in
      association with CEBPB. IFNG-stimulated proteolytic cleavage of ATF6, and MAPK1/3
      (ERK2/1)-dependent phosphorylation of CEBPB together control the expression of
      Dapk1. Consistent with their requirement for DAPK1 expression, IFNG fails to
      induce autophagy in cells lacking either Atf6 or Cebpb. More importantly, the
      Atf6(-/-) mice are highly susceptible to lethal bacterial infections due to a
      loss of autophagy. This study reported a connection between ER stress and
      autophagy in mediating antibacterial defenses.

PMID- 22874567
TI  - Autophagy is a protective response to ethanol neurotoxicity.
AB  - Ethanol is a neuroteratogen and neurodegeneration is the most devastating
      consequence of developmental exposure to ethanol. The mechanisms underlying
      ethanol-induced neurodegeneration are complex. Ethanol exposure produces reactive
      oxygen species (ROS) which cause oxidative stress in the brain. We hypothesized
      that ethanol would activate autophagy to alleviate oxidative stress and
      neurotoxicity. Our results indicated that ethanol increased the level of the
      autophagic marker Map1lc3-II (LC3-II) and upregulated LC3 puncta in SH-SY5Y
      neuroblastoma cells. It also enhanced the levels of LC3-II and BECN1 in the
      developing brain; meanwhile, ethanol reduced SQSTM1 (p62) levels. Bafilomycin
      A(1), an inhibitor of autophagosome and lysosome fusion, increased p62 levels in
      the presence of ethanol. Bafilomycin A(1) and rapamycin potentiated ethanol
      increased LC3 lipidation, whereas wortmannin and a BECN1-specific shRNA inhibited
      ethanol-promoted LC3 lipidation. Ethanol increased mitophagy, which was also
      modulated by BECN1 shRNA and rapamycin. The evidence suggested that ethanol
      promoted autophagic flux. Activation of autophagy by rapamycin reduced ethanol
      induced ROS generation and ameliorated ethanol-induced neuronal death in vitro
      and in the developing brain, whereas inhibition of autophagy by wortmannin and
      BECN1-specific shRNA potentiated ethanol-induced ROS production and exacerbated
      ethanol neurotoxicity. Furthermore, ethanol inhibited the MTOR pathway and
      downregulation of MTOR offered neuroprotection. Taken together, the results
      suggest that autophagy activation is a neuroprotective response to alleviate
      ethanol toxicity. Ethanol modulation of autophagic activity may be mediated by
      the MTOR pathway.

PMID- 22874568
TI  - Receptor protein complexes are in control of autophagy.
AB  - In autophagic processes a variety of cargos is delivered to the degradative
      compartment of cells. Recent progress in autophagy research has provided support
      for the notion that when autophagic processes are operating in selective mode, a
      receptor protein complex will process the cargo. Here we present a concept of
      receptor protein complexes as comprising a functional tetrad of components: a
      ligand, a receptor, a scaffold and an Atg8 family protein. Our current
      understanding of each of the four components and their interaction in the context
      of cargo selection are considered in turn.

PMID- 22874577
TI  - Stress, inflammation, and aging.

PMID- 22874569
TI  - Depletion of L-arginine induces autophagy as a cytoprotective response to
      endoplasmic reticulum stress in human T lymphocytes.
AB  - L-arginine (L-Arg) deficiency results in decreased T-cell proliferation and
      impaired T-cell function. Here we have found that L-Arg depletion inhibited
      expression of different membrane antigens, including CD247 (CD3zeta), and led to
      an ER stress response, as well as cell cycle arrest at G(0)/G(1) in both human
      Jurkat and peripheral blood mitogen-activated T cells, without undergoing
      apoptosis. By genetic and biochemical approaches, we found that L-Arg depletion
      also induced autophagy. Deprivation of L-Arg induced EIF2S1 (eIF2alpha), MAPK8
      (JNK), BCL2 (Bcl-2) phosphorylation, and displacement of BECN1 (Beclin 1) binding
      to BCL2, leading to autophagosome formation. Silencing of ERN1 (IRE1alpha)
      prevented the induction of autophagy as well as MAPK8 activation, BCL2
      phosphorylation and XBP1 splicing, whereas led T lymphocytes to apoptosis under L
      Arg starvation, suggesting that the ERN1-MAPK8 pathway plays a major role in the
      activation of autophagy following L-Arg depletion. Autophagy was required for
      survival of T lymphocytes in the absence of L-Arg, and resulted in a reversible
      process. Replenishment of L-Arg made T lymphocytes to regain the normal cell
      cycle profile and proliferate, whereas autophagy was inhibited. Inhibition of
      autophagy by ERN1, BECN1 and ATG7 silencing, or by pharmacological inhibitors,
      promoted cell death of T lymphocytes incubated in the absence of L-Arg. Our data
      indicate for the first time that depletion of L-Arg in T lymphocytes leads to a
      reversible response that preserves T lymphocytes through ER stress and autophagy,
      while remaining arrested at G(0)/G(1). Our data also show that the L-Arg
      depletion-induced ER stress response could lead to apoptosis when autophagy is
      blocked.

PMID- 22874578
TI  - Independent application of the Sacco Disaster Triage Method to pediatric trauma
      patients.
AB  - INTRODUCTION: Though many mass-casualty triage methods have been proposed, few
      have been validated in an evidence-based manner. The Sacco Triage Method (STM)
      has been shown to accurately stratify adult victims of blunt and penetrating
      trauma into groups of increasing mortality risk. However, it has not been
      validated for pediatric trauma victims. PURPOSE: Evaluate the STM's performance
      in pediatric trauma victims. METHODS: Records from the United States' National
      Trauma Data Base, a registry of trauma victims developed by the American College
      of Surgeons, were extracted for the 2007-2009 reporting years. Patients <= 18
      years of age transported from a trauma scene with complete initial scene data
      were included in the analysis. Sacco triage scores were assigned to each registry
      patient, and receiver-operator curves were developed for predicting mortality,
      along with several secondary outcomes. Area under the receiver-operator curve
      (AUC) was the main outcome statistic. Sensitivity analysis was performed using a
      Sacco score without age adjustment, using blunt versus penetrating trauma, and
      using patients <12 years of age. RESULTS: There were 210,175 pediatric records,
      of which 90,037 had complete data for analysis. The STM with age adjustment
      predicted pediatric trauma mortality with an AUC of 0.933 (95% CI: 0.925-0.940).
      Without the age adjustment term, it predicted mortality with an AUC of 0.924 (95%
      CI: 0.916-0.933). The STM with age adjustment predicted blunt trauma mortality in
      72,467 patients with an AUC of 0.938 (95% CI: 0.929-0.947) and penetrating trauma
      mortality in 10,099 patients with an AUC of 0.927 (95% CI: 0.911-0.943). These
      findings did not change significantly when analysis was limited to patients <12
      years of age. The Sacco Triage Method was also predictive of some secondary
      outcomes, such as major injury and death on arrival to the emergency department.
      CONCLUSION: The Sacco Triage Method, with or without its age adjustment term, was
      a highly accurate predictor of mortality in pediatric trauma patients in this
      registry database. This triage method appears to be a valid strategy for the
      prioritization of injured children.

PMID- 22874579
TI  - Dynamic neural systems enable adaptive, flexible memories.
AB  - Almost all studies on memory formation have implicitly put forward a rather
      static view on memory. However, memories are not stable but sensitive to changes
      over time. Here we argue that memory alterations arise from the inherent
      predictive function of memory. Within this framework, we draw an analogy between
      the lateral temporal-lateral prefrontal system that supports prediction based on
      simple stimulus-response associations and propose that a similar system centring
      on the hippocampus and medial prefrontal cortex (mPFC) exists for complex
      episodic memories. We consider the hippocampus to be elementary for regularity
      detection and the mPFC for regularity storage together with response options,
      which form the basis of abstract knowledge. As such, abstract knowledge can come
      to guide behaviour in novel situations that only share partial overlap with
      episodic experiences that have given rise to the formation of abstract knowledge.
      Furthermore, we suggest that systems consolidation and sleep contribute to the
      formation of abstract knowledge, and that abstract knowledge can function as pre
      existing schemas to the encoding of novel memories. Finally, we discuss that
      reconsolidation supports the updating of memories to optimize prediction. We
      accentuate that memory formation requires dynamic interactions between brain
      regions, and that rapid formation of detailed memories depends on synaptic weight
      changes, whereas rather stable abstract knowledge is supported by cortico
      cortical rewiring. Together, we attempt explaining that apparent memory
      alterations and distortions are adaptive.

PMID- 22874580
TI  - Annotating the protein-RNA interaction sites in proteins using evolutionary
      information and protein backbone structure.
AB  - RNA-protein interactions play important roles in various biological processes.
      The precise detection of RNA-protein interaction sites is very important for
      understanding essential biological processes and annotating the function of the
      proteins. In this study, based on various features from amino acid sequence and
      structure, including evolutionary information, solvent accessible surface area
      and torsion angles (phi, psi) in the backbone structure of the polypeptide chain,
      a computational method for predicting RNA-binding sites in proteins is proposed.
      When the method is applied to predict RNA-binding sites in three datasets: RBP86
      containing 86 protein chains, RBP107 containing 107 proteins chains and RBP109
      containing 109 proteins chains, better sensitivities and specificities are
      obtained compared to previously published methods in five-fold cross-validation
      tests. In order to make further examination for the efficiency of our method, the
      RBP107 dataset is used as training set, RBP86 and RBP109 datasets are used as the
      independent test sets. In addition, as examples of our prediction, RNA-binding
      sites in a few proteins are presented. The annotated results are consistent with
      the PDB annotation. These results show that our method is useful for annotating
      RNA binding sites of novel proteins. 

PMID- 22874581
TI  - Missed opportunities: despite improvement in use of cardioprotective medications
      among patients with lower-extremity peripheral artery disease, underuse remains.
AB  - BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of
      cardiovascular events and benefit from aggressive secondary prevention; however,
      changes in the use of cardioprotective medications after incident diagnosis of
      PAD have not been well described. METHODS AND RESULTS: We used Danish nationwide
      administrative registries (2000-2007) to identify 2 groups with incident PAD: PAD
      alone (n=34 160) and PAD with history of coronary artery disease (CAD) (n=9570).
      With the use of a comparator with incident CAD alone (n=154 183), we assessed
      temporal trends and comparative use of cardioprotective medications. Relative
      differences in medication use were examined by using multivariable logistic
      regression. Use of medications improved temporally among both groups: for PAD
      alone, any antiplatelet use increased from 29% to 59% from 2000 to 2007
      (P<0.0001), whereas statin use increased 6-fold (9%-56%; P<0.0001). However, use
      of these therapies by 18 months after incident diagnosis for both PAD groups
      remained modest and lower in comparison with CAD alone (any antiplatelet, 53%
      versus 66%; statins, 40% versus 52%; angiotensin-converting enzyme inhibitors,
      20% versus 29%). Relative to CAD alone, patients with PAD alone were less likely
      to use any antiplatelet (adjusted odds ratio, 0.50; 95% confidence interval, 0.49
      0.52), statins (adjusted odds ratio, 0.50; 95% confidence interval, 0.48-0.52),
      or angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.51; 95%
      confidence interval, 0.49-0.53) by 18 months. CONCLUSIONS: Despite improvement in
      the use of cardioprotective medications over time, patients with PAD alone remain
      less likely than those with CAD alone to use these agents.

PMID- 22874582
TI  - Medical management of peripheral arterial disease: bridging the "gap"?

PMID- 22874583
TI  - Genetic amplification and the individualization of the parent-child relationship
      across adolescence.
AB  - BACKGROUND: Many psychological traits become increasingly influenced by genetic
      factors throughout development, including several that might intuitively be seen
      as purely environmental characteristics. One such trait is the parent-child
      relationship, which is associated with a variety of socially significant
      outcomes, including mental health and criminal behavior. Genetic factors have
      been shown to partially underlie some of these associations, but the changing
      role of genetic influence over time remains poorly understood. METHOD: Over 1000
      participants in a longitudinal twin study were assessed at three points across
      adolescence with a self-report measure regarding the levels of warmth and
      conflict in their relationships with their parents. These reports were analyzed
      with a biometric growth curve model to identify changes in genetic and
      environmental influences over time. RESULTS: Genetic influence on the child
      reported relationship with parent increased throughout adolescence, while the
      relationship's quality deteriorated. The increase in genetic influence resulted
      primarily from a positive association between genetic factors responsible for the
      initial relationship and those involved in change in the relationship over time.
      By contrast, environmental factors relating to change were negatively related to
      those involved in the initial relationship. CONCLUSIONS: The increasing genetic
      influence seems to be due to early genetic influences having greater freedom of
      expression over time whereas environmental circumstances were decreasingly
      important to variance in the parent-child relationship. We infer that the parent
      child relationship may become increasingly influenced by the particular
      characteristics of the child (many of which are genetically influenced),
      gradually displacing the effects of parental or societal ideas of child rearing.

PMID- 22874584
TI  - Exploring dietary patterns, obesity and sources of bias: the Vasterbotten
      Intervention Programme (VIP).
AB  - OBJECTIVE: Dietary patterns capture the overall diet and thereby provide
      information on how nutrients are consumed in combinations, and have been
      suggested to be a better method than studying single nutrients. The present study
      explored the relationship between dietary patterns at baseline and incidence of
      obesity at 10-year follow-up in women. DESIGN: A longitudinal study using
      baseline measurements from 1992-1996, including food intake, medication,
      heredity, socio-economic status, lifestyle and measured body composition, and
      follow-up data collected in 2002-2006 including measured body composition.
      SETTING: Data from the Vasterbotten Intervention Programme (VIP) in Sweden.
      SUBJECTS: A total of 6545 initially non-obese women aged 30-50 years. RESULTS:
      Among women reporting plausible energy intakes, the 'Fruit and vegetables
      cluster' predicted the highest incidence of obesity (OR = 1.76, 95 % CI 1.11,
      2.76; P = 0.015) compared with women in the other food pattern groups combined.
      When adjusting for metabolic factors and BMI at baseline, the risk for obesity in
      the 'Fruit and vegetables cluster' was attenuated to non-significance. In
      contrast, high intake of fruit per se was associated with a decreased risk of
      developing obesity (OR = 0.69, 95 % CI 0.51, 0.91; P = 0.010). CONCLUSIONS:
      Dietary pattern groups identified by cluster analysis are likely to reflect
      characteristics in addition to diet, including lifestyle, previous and current
      health status and risk factors for future disease, whereas intake of fruit per se
      was a stable indicator and less affected by baseline characteristics. These
      results underscore the need for complementary methods in understanding diet
      disease relationships.

PMID- 22874585
TI  - Direct and glia-mediated effects of GABA on development of central olfactory
      neurons.
AB  - Previously studied for its role in processing olfactory information in the
      antennal lobe, GABA also may shape development of the olfactory pathway, acting
      either through or on glial cells. Early in development, the dendrites of
      GABAergic neurons extend to the glial border that surrounds the nascent olfactory
      lobe neuropil. These neuropil glia express both GABAA and GABAB receptors, about
      half of the glia in acute cultures responded to GABA with small outward currents,
      and about a third responded with small transient increases in intracellular
      calcium. The neuronal classes that express GABA in vivo, the local interneurons
      and a subset of projection neurons, also do so in culture. Exposure to GABA in
      culture increased the size and complexity of local interneurons, but had no
      effect on glial morphology. The presence of glia alone did not affect neuronal
      morphology, but in the presence of both glia and GABA, the growth-enhancing
      effects of GABA on cultured antennal lobe neurons were eliminated. Contact
      between the glial cells and the neurons was not necessary. Operating in vivo,
      these antagonistic effects, one direct and one glia mediated, could help to
      sculpt the densely branched, tufted arbors that are characteristic of neurons
      innervating olfactory glomeruli.

PMID- 22874586
TI  - Healthcare delivery: which way do we go?

PMID- 22874587
TI  - Mini-Mental State Examination sentence writing among community-dwelling elderly
      adults in Brazil: text fluency and grammar complexity.
AB  - BACKGROUND: In normal aging, the decrease in the syntactic complexity of written
      production is usually associated with cognitive deficits. This study was aimed to
      analyze the quality of older adults' textual production indicated by verbal
      fluency (number of words) and grammatical complexity (number of ideas) in
      relation to gender, age, schooling, and cognitive status. METHODS: From a
      probabilistic sample of community-dwelling people aged 65 years and above (n =
      900), 577 were selected on basis of their responses to the Mini-Mental State
      Examination (MMSE) sentence writing, which were submitted to content analysis;
      323 were excluded as they left the item blank or performed illegible or not
      meaningful responses. Education adjusted cut-off scores for the MMSE were used to
      classify the participants as cognitively impaired or unimpaired. Total and
      subdomain MMSE scores were computed. RESULTS: 40.56% of participants whose
      answers to the MMSE sentence were excluded from the analyses had cognitive
      impairment compared to 13.86% among those whose answers were included. The
      excluded participants were older and less educated. Women and those older than 80
      years had the lowest scores in the MMSE. There was no statistically significant
      relationship between gender, age, schooling, and textual performance. There was a
      modest but significant correlation between number of words written and the scores
      in the Language subdomain. CONCLUSIONS: Results suggest the strong influence of
      schooling and age over MMSE sentence performance. Failing to write a sentence may
      suggest cognitive impairment, yet, instructions for the MMSE sentence, i.e. to
      produce a simple sentence, may limit its clinical interpretation.

PMID- 22874588
TI  - Can theory be embedded in visual interventions to promote self-management? A
      proposed model and worked example.
AB  - Nurses are increasingly involved in a range of strategies to encourage patient
      behaviours that improve self-management. If nurses are to be involved in, or
      indeed lead, the development of such interventions then processes that enhance
      the likelihood that they will lead to evidence that is both robust and usable in
      practice are required. Although behavioural interventions have been predominantly
      based on written text or the spoken word increasing numbers are now drawing on
      visual media to communicate their message, despite only a growing evidence base
      to support it. The use of such media in health interventions is likely to
      increase due to technological advances enabling easier and cheaper production,
      and an increasing social preference for visual forms of communication. However,
      the development of such media is often highly pragmatic and developed intuitively
      rather than with theory and evidence informing their content and form. Such a
      process may be at best inefficient and at worst potentially harmful. This paper
      performs two functions. Firstly, it discusses and argues why visual based
      interventions may be a powerful media for behaviour change; and secondly, it
      proposes a model, developed from the MRC Framework for the Development and
      Evaluation of Complex Interventions, to guide the creation of theory informed
      visual interventions. It employs a case study of the development of an
      intervention to motivate involvement in a lifestyle intervention among people
      with increased cardiovascular risk. In doing this we argue for a step-wise model
      which includes: (1) the identification of a theoretical basis and associated
      concepts; (2) the development of visual narrative to establish structure; (3) the
      visual rendering of narrative and concepts; and (4) the assessment of
      interpretation and impact among the intended patient group. We go on to discuss
      the theoretical and methodological limitations of the model.

PMID- 22874589
TI  - Reliability of the nursing care hour measure: a descriptive study.
AB  - BACKGROUND: The nursing care hour has become an international standard unit of
      measure in research where nurse staffing is a key variable. Until now, there have
      been no studies verifying whether nursing care hours obtained from hospital data
      sources can be collected reliably. OBJECTIVES: To examine the processes used by
      hospitals to generate nursing care hour data and to evaluate inter-rater
      reliability and guideline compliance with standards of the National Database of
      Nursing Quality Indicators((r)) (NDNQI((r))) and the National Quality Forum.
      DESIGN AND SETTING: Two-phase descriptive study of all NDNQI hospitals that
      submitted data in third quarter of 2007. METHODS: Data for phase I came from an
      online survey created by the authors to ascertain the processes used by hospitals
      to collect nursing care hours and their compliance with standardized data
      collection guidelines. In phase II, inter-rater reliability was measured using
      intra-class correlations between nursing care hours generated from clock hour
      files submitted to the study team by participants' payroll/accounting departments
      and aggregated data submitted previously. RESULTS: Phase I data were obtained
      from a total of 714 respondents. Nearly half (48%) of all sites use payroll
      records to obtain nursing care hour data and 70% use one of the standardized
      methods for converting the bi-weekly hours into months. Unit secretaries were
      reportedly included in NCH by 17.4% of respondents and only 26.2% of sites could
      accurately identify the point at which newly hired nurses should be included. The
      phase II findings (n=11) support the ability of two independent raters to obtain
      similar results when calculating total nursing care hours according to standard
      guidelines (ICC=0.76-0.99). CONCLUSIONS: Although barriers exist, this study
      found support for hospitals' abilities to collect reliable nursing care hour
      data.

PMID- 22874590
TI  - MAP optimization as a predictor of cochlear implant outcomes in children with
      narrow internal auditory canal.
AB  - OBJECTIVES: The purposes of this study were to investigate the auditory
      performance and MAP characteristics of implanted children with narrow internal
      auditory canal (IAC), and to examine the clinical usefulness of MAP optimization
      as a predictor of their cochlear implant (CI) outcomes by analyzing their
      auditory performance and habilitation methods in relation to MAP optimization.
      METHODS: Eight children with narrow IAC who had used a CI over 3 years were
      included. We retrospectively examined their auditory performance and MAPs.
      Auditory performance was measured by the Categories of Auditory Performance (CAP)
      and monosyllabic word tests before and after implantation. The relationship
      between auditory performance and MAP parameters was explored, and their
      habilitation methods were analyzed. RESULTS: Mean CAP scores improved from .25
      preoperatively to 3.5 3 years postoperatively. Mean scores for monosyllabic word
      tests improved from 0% preoperatively to 27.8% 3 years postoperatively. The
      children used MAPs with a wider pulse width than the default setting. Four
      children using optimal MAPs achieved open-set speech perception, so were trained
      in the oral approach. The other four using suboptimal MAPs because of non
      auditory stimulation achieved no open-set speech perception, so were trained in
      the total communication approach. CONCLUSIONS: MAP optimization had a predictable
      value in determining the postoperative performance of children with narrow IAC
      who received a CI. The most suitable habilitation method can be determined early
      after implantation by identifying the presence of MAP optimization.

PMID- 22874591
TI  - A preliminary study of computer assisted evaluation of congenital tracheal
      stenosis: a new tool for surgical decision-making.
AB  - OBJECTIVE: Congenital tracheal stenosis is a rare but severe condition with
      tracheal narrowing. There is no absolute correlation between luminal diameter and
      prognosis, and therapeutic decisions are difficult for intermediate cases. The
      aim of this study was to develop a dynamic model of the ventilatory consequences
      of congenital tracheal stenosis using computational fluid dynamics. METHODS: In 8
      children with congenital tracheal stenosis and 1 healthy child, 3-dimensional
      geometries of the trachea were constructed with computed tomography images and
      specialized software (ITK-SNAP). Airflow simulations were performed for each
      geometry using 2 physiologic inhalation flow rates under steady and laminar flow
      conditions. Flow velocity, static and total airway pressure, and pressure drop
      across the entire trachea were determined. RESULTS: In the patients with
      congenital tracheal stenosis, the pressure drop from the tracheal inlet to
      outlet, at flow rate 3L/min, ranged from 14 to 430Pa; the pressure drop at flow
      rate 7.3L/min ranged from 60 to 1825Pa. The pressure drop enabled a
      classification based on the severity of stenosis. The classification based on
      pressure drop was retrospectively consistent with the classification based on
      clinical data from the patients. CONCLUSIONS: Simulations with computational
      fluid dynamics may provide an objective method to evaluate the severity of the
      symptoms in patients with congenital tracheal stenosis and may help guide
      treatment.

PMID- 22874592
TI  - Comparison of differentially expressed genes involved in drought response between
      two elite rice varieties.

PMID- 22874593
TI  - A new mode of cell cycle stimulation: cyclin E and CDK2-mediated cytoplasmic
      retention of repressive E2F complexes.

PMID- 22874594
TI  - "Double hit" makes the difference.

PMID- 22874595
TI  - A critical role for TORC1 in cellular senescence.

PMID- 22874596
TI  - Timeless tunes: replicating happy endings.

PMID- 22874597
TI  - Fenugreek seed affects intestinal microbiota and immunological variables in
      piglets after weaning.
AB  - Fenugreek seed has been shown to affect the intestinal microbiota and
      immunological responses in animals. A feeding trial with male castrated piglets
      was performed over 28 d without or with the addition of 1.5 g fenugreek seeds/kg
      complete diet in ten and eleven piglets, weaned at 21 d. In the intestinal tract,
      pH, lactate and SCFA were measured as major bacterial metabolites. Immune cell
      phenotypes, phagocytic activity and lymphocyte proliferation after stimulation
      with pokeweed mitogen, concanavalin A and phytohaemagglutinin M were measured by
      flow cytometry. Health status and performance of the piglets were not affected by
      fenugreek. The pH in the caecum and colon were reduced compared with the control
      (P< 0.05). Higher concentrations of l-lactic acid were recorded in the small
      intestinal digesta (average concentrations from the duodenum, jejunum and ileum;
      P< 0.05), while the concentrations of SCFA remained unchanged except an increase
      in n-butyric acid in colon contents (P< 0.05). The piglets fed the fenugreek diet
      had higher Lactobacillus and clostridium cluster I concentrations and lower
      Escherichia, Hafnia and Shigella concentrations in the small intestine. The
      addition of fenugreek increased the relative concentration of the gammadelta T
      cell population (TCR1+CD8alpha-) in the blood with a simultaneous reduction of
      antigen-presenting cells (MHCII+CD5-) (P< 0.05). Proliferation rate and
      phagocytosis activity of monocytes were not affected by the additive. In
      conclusion, fenugreek seeds might be interesting as a feed ingredient for young
      piglets due to their effects on the intestinal microbiota and immunological
      variables. The impact on performance and animal health has to be further
      evaluated.

PMID- 22874598
TI  - Management of deeply infiltrating endometriosis involving the rectum.
AB  - BACKGROUND: Rectal endometriosis can cause debilitating symptoms. Rectal
      resection in this setting has been shown to improve symptoms; however, there
      remain some reservations about this intervention because of the risk of
      complications such as anastomotic leak and rectovaginal fistula. OBJECTIVE: The
      aim of this study is to review our experience with rectal resection in patients
      with rectal endometriosis. DATA SOURCES: Hospital records and prospectively
      maintained electronic databases of an endogynecologist and colorectal surgeon
      were reviewed. STUDY SELECTION: This is a retrospective study of consecutive
      patients who underwent rectal resection for endometriosis from 2001 to 2010.
      INTERVENTIONS: All patients underwent either disc or segmental resection of the
      rectum. MAIN OUTCOME MEASURES: Outcomes of interest were operative complications
      and recurrence requiring surgical reintervention. RESULTS: Ninety-one patients
      underwent 92 resections for endometriosis. Sixty-five (71%) were disc resections,
      25 (27%) were segmental resections, and 1 patient underwent both disc and
      segmental resections. Eighty-one (88%) procedures were completed
      laparoscopically. Patients requiring segmental resection had more extensive
      disease, and this was associated with open conversion (p <= 0.0001). Average
      duration of procedure was 209 minutes. Three patients (3%) required defunctioning
      ileostomies. Intramural endometriosis was confirmed in 96.7% of specimens.
      Complications occurred in 13 patients (15%); 4 were minor. Three patients had
      small pelvic collections treated with antibiotics, 5 patients required
      transfusion for bleeding (3 intraoperative, 2 anastomotic bleeds that settled
      conservatively), and 1 patient sustained ureteric injury that was reimplanted
      with no sequelae. None had anastomotic leak or rectovaginal fistula. Ten patients
      (11%) required reintervention for recurrent symptoms. Of these, 8 (8.8%) patients
      were found to have recurrent endometriosis. No correlation could be found between
      involved margins on pathology and need for redo surgery. LIMITATIONS: : This
      study is limited by its retrospective nature. CONCLUSIONS: Laparoscopic rectal
      resection for deeply infiltrative endometriosis is feasible and safe, and it
      provides durable symptom control with acceptable recurrence rates.

PMID- 22874599
TI  - Laparoscopic lavage for perforated diverticulitis:  a population analysis.
AB  - BACKGROUND: Laparoscopic lavage has shown promising results in nonfeculent
      perforated diverticulitis. It is an appealing strategy; it avoids the
      complications associated with resection. However, there has been some reluctance
      to widespread uptake because of the scarcity of large-scale studies. OBJECTIVE:
      This study investigated national trends in management of perforated
      diverticulitis. DESIGN: This retrospective population study used an Irish
      national database to identify patients acutely admitted with diverticulitis, as
      defined by the International Classification of Diseases. Demographics,
      procedures, comorbidities, and outcomes were obtained for the years 1995 to 2008.
      SETTINGS: The study was conducted in Ireland. PATIENTS: Patients with
      International Classification of Diseases codes corresponding to diverticulitis
      who underwent operative intervention were included. MAIN OUTCOME MEASURES: The
      primary outcome was mortality, and secondary outcomes were length of stay and
      postoperative complications. RESULTS: Two thousand four hundred fifty-five
      patients underwent surgery for diverticulitis, of whom 427 underwent laparoscopic
      lavage. Patients selected for laparoscopic lavage had lower mortality (4.0% vs
      10.4%, p < 0.001), complications (14.1% vs 25.0%, p < 0.001), and length of stay
      (10 days vs 20 days, p < 0.001) than those requiring laparotomy/resection.
      Patients older than 65 years were more likely to die (OR 4.1, p < 0.001), as were
      those with connective tissue disease (OR 7.3, p < 0.05) or chronic kidney disease
      (OR 8.0, p < 0.001). LIMITATIONS: This retrospective study is limited by the
      quality of data obtained and is subject to selection bias. Furthermore, the lack
      of disease stratification means it is not possible to identify the extent of
      peritonitis; feculent peritonitis has worse outcomes and is not likely to be
      included in the lavage group. CONCLUSIONS: The number of patients selected for
      laparoscopic lavage in perforated diverticulitis is increasing, and the outcomes
      in this study are comparable to other reports. Those patients in whom
      laparoscopic lavage alone was suitable had lower mortality and morbidity than
      those in whom resection was considered necessary.

PMID- 22874600
TI  - Long-term results after restorative proctocolectomy with ileal pouch-anal
      anastomosis at a young age.
AB  - BACKGROUND: Restorative proctocolectomy with IPAA is an optimal surgical
      treatment for patients with familial adenomatous polyposis and therapy resistant
      ulcerative colitis, few data are available on long-term results in patients who
      have undergone this operation at a young age. OBJECTIVE: The aim of this study
      was to investigate long-term functional outcome, quality of life, body image, and
      sexual function after restorative proctocolectomy with IPAA in young patients
      with familial adenomatous polyposis or ulcerative colitis. DESIGN, SETTINGS, AND
      PATIENTS: The study consisted of a retrospective review of medical records and
      questionnaire follow-up of 26 consecutive patients with familial adenomatous
      polyposis or ulcerative colitis who had undergone surgery between January 1992
      and October 2008 at the Maastricht University Medical Center, were aged 10 to 24
      years at the time of surgery, and had at least 1 year of follow-up after surgery.
      MAIN OUTCOME MEASURES: We reviewed medical records from an institutional database
      regarding surgical procedures and short- and long-term complications. At the end
      of 2009, validated questionnaires covering bowel function (Colorectal Functional
      Outcome Questionnaire), quality of life (Short Form-36 and Gastrointestinal
      Quality of Life Index), body image and cosmesis (Body Image Questionnaire), and
      sexual function (International Index of Erectile Function for men and Female
      Sexual Function Index for women) were mailed to patients. RESULTS: Median age at
      surgery was 18 years, and median follow-up was 12.5 (range, 2-18) years. Long
      term colorectal complications occurred in 23 patients (88%), and were directly
      related to the surgery in 20 patients (77%). Five patients needed pouch excision.
      The questionnaire response rate was 88%. Bowel function, quality-of-life, and
      body image and cosmesis scores were all lower in patients than in historical
      normal control populations. Men did not report impotence or retrograde
      ejaculation, but 50% of women reported sexual dysfunction. LIMITATIONS: This was
      a retrospective study in a small number of patients from a single institution
      with no comparison groups. CONCLUSIONS: Restorative proctocolectomy with IPAA can
      be performed in young patients with an acceptable functional outcome, but at the
      cost of relatively high complication rates, poor body image and cosmesis, and a
      high rate of sexual dysfunction in women. Because young patients undergoing this
      surgical procedure may experience negative long-term effects, surgeons should be
      aware of all potential consequences, inform patients as to what to expect, and
      ensure long-term follow-up to deal with long-term complications.

PMID- 22874601
TI  - Impact of chronic kidney disease on outcomes of surgical resection for primary
      colorectal cancer:  a retrospective cohort review.
AB  - BACKGROUND: Chronic kidney disease, a disease entity increasing in number, may be
      an obstacle in various aspects of treatment for malignant neoplasm, such as
      perisurgical management and implementation of chemotherapy. OBJECTIVE: The aim of
      this study was to evaluate both short- and long-term outcomes of patients with
      colorectal cancer who have chronic kidney disease. DESIGN: This study is a
      retrospective cohort study of patients. SETTINGS: This study as conducted at an
      academic tertiary hospital in Japan. PATIENTS AND INTERVENTIONS: We investigated
      1127 consecutive patients with stages 0 to III primary colorectal cancer who
      underwent curative resection in our department from January 2001 to December
      2010. Based on estimated glomerular filtration rate, patients were classified
      into stages 0 to 2 (including normal renal function, 882 patients, 78.2%), stages
      3 to 4 (226 patients, 20.1%), or stage 5 chronic kidney disease (19 patients,
      1.7%). MAIN OUTCOME MEASURES: Clinicopathological data, perioperative course,
      frequencies of postoperative complications, adjuvant chemotherapy, and recurrence
      free and overall survivals after surgery for colorectal cancer were compared
      among the 3 different chronic kidney disease stage groups. RESULTS: Patients with
      chronic kidney disease stage 5 frequently experienced diabetes mellitus and
      cardiovascular comorbidities. They were also hypoalbuminemic and anemic and more
      likely to receive blood transfusions, although estimated blood loss was smaller
      during surgery than in the other patients. Perioperative cardiovascular
      complications were more frequent in the chronic kidney disease stages 3 to 4 and
      5 groups (5.3%) than those in the stages 0 to 2 group (0.8%, p < 0.0001).
      However, the frequencies of other complications were similar. There were no
      differences in the frequency of adjuvant chemotherapy and recurrence-free
      survival among different chronic kidney disease stages; in contrast, the chronic
      kidney disease stage 5 group showed a poorer overall survival. LIMITATIONS: : The
      study is limited by its retrospective nature. CONCLUSIONS: From these data, we
      conclude that surgical resection for colorectal cancer in patients with chronic
      kidney disease can be performed with acceptable outcomes.

PMID- 22874602
TI  - Risk factors for postoperative intra-abdominal septic complications after bowel
      resection in patients with Crohn's disease.
AB  - BACKGROUND: Postoperative intra-abdominal septic complications are a serious
      concern with regard to postoperative morbidity and mortality in Crohn's disease.
      OBJECTIVE: The aim of this study was to identify the clinical variables that
      potentially impact the risk of intra-abdominal septic complications in patients
      with Crohn's disease, as well al analyze the short-term prognosis in patients
      with postoperative intra-abdominal septic complications. DESIGN: This study is a
      retrospective review with the use of hospital medical records. SETTINGS: This
      investigation was conducted at a single-institution, tertiary referral center in
      Tokyo, Japan. PATIENTS: We reviewed 550 patients that had undergone 728
      intestinal anastomoses during 633 operations for primary or recurrent Crohn's
      disease between January 2005 and December 2010. Postoperative intra-abdominal
      septic complications were defined as anastomotic leakage or intra-abdominal
      abscesses occurring within 1 month after surgery. MAIN OUTCOME MEASURE: Twenty
      four clinical variables were evaluated as potential risk factors for
      postoperative intra-abdominal septic complications. These factors were analyzed
      by use of univariate and multivariate methods. RESULTS: Postoperative intra
      abdominal septic complications occurred in 17 cases (2.7%), with no fatalities.
      Of the 17 patients, 13 had anastomotic leakage and 4 had intra-abdominal
      abscesses. In the univariate and multivariate analyses, penetrating type (p =
      0.014), operation time >180 minutes (p = 0.004), and handsewn anastomoses (p =
      0.005) were significantly independent risk factors for postoperative intra
      abdominal septic complications. Patients experiencing intra-abdominal septic
      complications had significantly higher 1-year reoperation rates (41.2%) than
      patients without intra-abdominal septic complications (2.3%, p < 0.0001).
      LIMITATIONS: This study was limited by being a retrospective review, and the
      details regarding postoperative complications other than intra-abdominal septic
      complications were not completely available. CONCLUSIONS: Penetrating type,
      operation time >180 minutes, and handsewn anastomoses significantly increased the
      risk of postoperative intra-abdominal septic complications in Crohn's disease.
      Postoperative intra-abdominal septic complications had a negative influence on
      the short-term outcome in Crohn's disease.

PMID- 22874603
TI  - Permanent end-sigmoid colostomy through the extraperitoneal route prevents
      parastomal hernia after laparoscopic abdominoperineal resection.
AB  - BACKGROUND: The prevalence of a paracolostomy hernia has been reported to be from
      10% to 50%, with serious impairment of the quality of life and sometimes life
      threatening morbidity in some cases. Most essential in avoiding the need for
      further treatment of an end-sigmoid colostomy is prevention of a parastomal
      hernia. OBJECTIVE: We examined the effects of the extraperitoneal route for stoma
      creation to prevent parastomal hernia after laparoscopic abdominoperineal
      resection for rectal neoplasms. DESIGN: This is a study of a retrospective
      cohort. SETTING AND PATIENTS: Data on a total 37 consecutive patients who
      underwent abdominoperineal resection from March 2005 to December 2010 in Kochi
      Health Sciences Center were examined retrospectively in this study. Group A
      included 22 patients whose stoma was created through the extraperitoneal route,
      and group B included 15 patients whose stoma was created through the
      transperitoneal route. MAIN OUTCOME MEASURES: The main outcome measures were the
      rate of parastomal hernia determined through CT and clinical examinations in the
      2 groups. RESULTS: In Group A, 1 case was diagnosed as having a parastomal
      hernia, whereas, in Group B, 5 cases were diagnosed by CT examination as having a
      parastomal hernia; the difference in incidence between the 2 groups was
      significant (p = 0.0305). Furthermore, median duration of the follow-up period
      between the latest CT examination and the primary operation was 722 days in group
      A, which was significantly longer than that in group B (442 days) (p = 0.001).
      LIMITATIONS: : This study was limited by its nonrandomized retrospective design.
      CONCLUSION: Group B developed parastomal hernia more frequently within a
      significantly shorter period. A permanent sigmoid colostomy created through the
      extraperitoneal route can prevent the incidence of parastomal hernia after
      laparoscopic abdominoperineal resection.

PMID- 22874604
TI  - The myth of informed consent in rectal cancer surgery:  what do patients retain?
AB  - BACKGROUND: Previous research in colorectal cancer has focused on survival,
      recurrence, and functional outcomes. Few have assessed the decisional needs of
      patients or the information patients are retaining from the informed consent
      process. OBJECTIVES: The aims of this study were to describe the decisional needs
      of adult patients with rectal cancer when deciding on the surgical treatment of
      their disease and to identify gaps in patients' recollection of the informed
      consent discussion. DESIGN: Face-to-face interviews were conducted with the use
      of a questionnaire based on the validated Ottawa Decision Support Framework Needs
      Assessment. SETTING: This study was performed at a university-based academic
      Cancer Assessment Center, in Ottawa, Ontario, Canada. PATIENTS: Adult patients
      with rectal cancer treated with low anterior resection or abdominoperineal
      resection were included. MAIN OUTCOME MEASURES: The primary outcomes measured
      were patients' knowledge and understanding of decision and their decisional
      needs. RESULTS: Thirty patients were interviewed between November 2009 and July
      2010. Eighty percent were male, with a median age of 65. None of the patients
      perceived having a choice of surgical options. When questioned about the main
      outcomes of rectal cancer surgery, 47% could not recall a preoperative discussion
      of risks to bowel function, 47% could not recall a preoperative discussion of
      risks to sexual function, and 57% could not recall a preoperative discussion of
      risks to urinary function. Patients would like information regarding functional
      outcomes, body image, and the immediate postoperative period. A minority of
      patients desire information regarding cure rate, need for a second surgery, or
      the ability of surgery to treat their symptoms. Patients would like information
      that is portable and trusted by their health care team that they can review at
      their own time. LIMITATIONS: To avoid introducing decisional conflict before
      surgery, patients were interviewed at the first postoperative visit. Preoperative
      informed consent discussions were not standardized. CONCLUSION: Despite a
      comprehensive educational oncology pathway, patients retain little of the
      informed consent discussion. This study highlights the dichotomy between the
      outcomes that surgeons and patients value most. The results of this study will
      guide future efforts to improve informed consent.

PMID- 22874605
TI  - Dynamic transperineal ultrasound in the workup of men with obstructed defecation:
      a pilot study.
AB  - BACKGROUND: Dynamic transperineal ultrasound has been used in women for the
      noninvasive investigation of functional disorders of the posterior pelvic floor,
      but its use in men has been limited by technical difficulties related to the
      consistency of the male perineum. OBJECTIVES: The aim of this study was to
      explore the efficacy of dynamic transperineal ultrasound in diagnosing posterior
      pelvic floor dysfunction in men. DESIGN: This is a study of diagnostic accuracy.
      SETTINGS: This study was performed at a public hospital. PATIENTS: Forty-six men
      with symptoms of obstructed defecation were included. INTERVENTIONS: All patients
      underwent dynamic transperineal ultrasound 1 week after standard defecography
      with manometric confirmation when rectoanal dyssynergy was observed. MAIN OUTCOME
      MEASURES: Images were obtained, and anorectal angles were measured under resting
      conditions and during maximal strain. The accuracy of the sonographic method in
      diagnosing pelvic floor alterations was assessed against defecography (reference
      method). RESULTS: : Anorectal angles measured with ultrasound and defecography
      were not significantly different under resting conditions or maximum strain.
      Sonographic and reference method findings were concordant in 41 (89.1%) of the
      cases (25 with rectoanal intussusceptions, 7 with rectorectal intussusceptions, 8
      with rectoanal dyssynergy, and 1 with rectorectal intussusception and
      dyssynergy). In 1 patient with rectoanal intussusception, dynamic transperineal
      ultrasound was nondiagnostic (low image quality probably due to dehydration of
      perineal tissues). Discordant dynamic transperineal ultrasound findings included
      normal findings in another patient with rectoanal intussusception, diagnosis of
      rectoanal intussusception in 2 men with rectorectal intussusception, and failure
      to detect dyssynergy in a second patient with rectorectal intussusception and
      dyssynergy. The sensitivity, specificity, and Cohen kappa indices for dynamic
      transperineal ultrasound were 92.6%, 90.5%, and 82% (rectoanal intussusception);
      81.8%, 100%, and 87% (rectorectal intussusception); 90%, 100%, and 93% (rectoanal
      dyssynergy). LIMITATIONS: This study was limited by its small size and by the
      absence of patients with other morphofunctional disorders associated with
      obstructed defecation. CONCLUSIONS: Dynamic transperineal ultrasound is
      potentially useful for diagnosis and follow-up of posterior pelvic floor
      dysfunction in men.

PMID- 22874606
TI  - Favorable long-term clinical outcome of uncovered D-weave stent placement as
      definitive palliative treatment for malignant colorectal obstruction.
AB  - BACKGROUND: Most self-expandable metallic stents for colorectal placement are
      uncovered because of the high migration rate of covered stents. However, the
      optimal stent design for colorectal use remains unclear. OBJECTIVE: The purpose
      of this study was to evaluate the efficacy and safety of a double-wire woven
      uncovered stent for definitive palliative treatment of malignant colorectal
      obstruction. DESIGN: This study was a prospective, single-arm, observational
      clinical study of patients enrolled between December 2005 and September 2010.
      SETTINGS: This study was conducted at a referral hospital in Japan. PATIENTS:
      Twenty-four consecutive patients with malignant colorectal obstruction were
      included in the study. INTERVENTIONS: A double-wire woven uncovered stent was
      placed by use of a standard through-the-scope endoscopic placement technique.
      MAIN OUTCOME MEASURES: Technical, initial clinical, and long-term clinical
      success were measured. Long-term clinical success was defined as sustained relief
      of obstructive symptoms without reintervention until the patient's death.
      RESULTS: The Karnofsky performance status score before stent placement was 60
      (median, interquartile range, 42.5-67.5). Twenty of 24 patients had primary
      colorectal cancer, and 4 had extracolorectal malignancies. The site of
      obstruction was the ascending colon in 10 patients, descending colon in 4
      patients, sigmoid colon in 7 patients, and rectum in 3 patients. Technical,
      initial, and long-term clinical success rates were 100%, 100%, and 83%. Median
      stent patency time was 149 days (interquartile range, 45-198 days). Median
      survival time after stent placement was 155 days (interquartile range, 68-231
      days). Four patients (17%) had negative outcomes including stent occlusion by
      tumor ingrowth (8%) and stent migration (8%). The highest Karnofsky performance
      status score after stent placement was 70 (median; interquartile range, 50-70).
      The Karnofsky performance status score improved after stent placement (p =
      0.002). LIMITATIONS: This study was limited because it was a single-arm, single
      center study, and it had a small sample size. CONCLUSIONS: Endoscopic placement
      of double-wire woven uncovered stents is effective and safe as definitive
      palliative treatment for patients with malignant colorectal obstruction.

PMID- 22874607
TI  - Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant
      combined modality therapy.
AB  - BACKGROUND: We have previously demonstrated the prognostic significance of rectal
      cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other
      cancers have reported that hypoxia influences response to neoadjuvant
      chemoradiation. OBJECTIVE: This study aimed to 1) characterize hypoxia-related
      protein expression in locally advanced rectal cancer before neoadjuvant
      chemoradiation, 2) determine the comodulation of hypoxia-related protein
      expression, and 3) evaluate the relationship between hypoxia-related protein
      expression and overall survival, time to recurrence, and tumor regression grade.
      DESIGN: Immunohistochemical analysis of 4 hypoxia-related proteins (HIF-1alpha,
      CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer
      biopsies. PATIENTS: : Eighty-five patients with locally advanced rectal cancer
      treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were
      included. MAIN OUTCOME MEASURES: The impact of hypoxia-related protein expression
      on outcome was evaluated by use of Cox proportional hazards model. Hypoxia
      related protein expression was correlated with tumor regression grade by use of
      Spearman correlation coefficients. RESULTS: Median follow-up was 54 months. CA-IX
      expression was associated with overall survival (p = 0.01). HIF-1alpha expression
      was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p =
      0.001). Hypoxia-related protein expression was not associated with time to
      recurrence or Mandard tumor regression grade. CONCLUSIONS: Elevated CA-IX
      expression may be associated with poorer overall survival in locally advanced
      rectal cancer treated by neoadjuvant chemoradiation and resection. The expression
      of the hypoxia-related proteins HIF-1alpha, VEGF, and GLUT-1 may be comodulated
      in locally advanced rectal cancer. Further studies are needed to evaluate the
      mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer
      response to neoadjuvant chemoradiation.

PMID- 22874608
TI  - Transanal endoscopic total mesorectal excision combined with single-port
      laparoscopy.
AB  - BACKGROUND: Rectal dissection using a conventional multiport laparoscopic
      approach involves risks due to technical difficulties, particularly in patients
      with a low tumor, a narrow pelvis, or obesity. OBJECTIVE: We describe a technique
      of transanal endoscopic low and middle rectal dissection with subsequent coloanal
      anastomosis via single-port laparoscopy, with the aim of reducing technical
      problems, increasing safety, and improving cosmesis after resection of rectal
      cancer. DESIGN AND SETTING: This was an observational study conducted in a large,
      tertiary care cancer center in France. PATIENTS: Consecutive patients with rectal
      adenocarcinoma requiring total mesorectal excision with a coloanal anastomosis
      were evaluated for eligibility to undergo the procedure. Patients were selected
      if they had 1 or more of the following risk factors: narrow pelvis, a voluminous
      prostate, or obesity. INTERVENTION: After an anal mucosectomy, the rectal wall
      was circumferentially transected above the external sphincter and a transanal
      trocar was introduced. The dissection of the mesorectum was completely performed
      via endoscopy up to the Douglas rectovesical pouch. A single port was inserted at
      the future site of the transient ileostomy, and a left colectomy and a
      lymphadenectomy were performed. The upper rectum dissection enabled joining the
      transanal rectal plane of dissection. Then the splenic flexure was completely
      mobilized and the specimen was extracted through the site of the future
      ileostomy. OUTCOME MEASURES: Operative time, blood loss, duration of hospital
      stay, and histopathologic variables (margins, number of harvested lymph nodes,
      grade of the mesorectal fascia dissection) were recorded, and the quality of the
      surgical plane was assessed. The Cleveland Clinic Florida (Wexner) fecal
      incontinence questionnaire was administered after ileostomy closure. RESULTS:
      Four consecutive male patients with rectal cancer in a narrow pelvis were treated
      with this new approach. No conversion (by laparotomy or multiport laparoscopy)
      was necessary. The pathologic variables were satisfactory and the Wexner scores
      indicated no severe incontinence after ileostomy closure. The postoperative
      follow-up was uneventful except for an anastomotic fistula which developed in 1
      patient and was treated without reoperation. LIMITATIONS: The study was limited
      by the small number of patients and the fact that no women and no obese patients
      were included. CONCLUSIONS: Rectal resection via the transanal approach combined
      with single-port laparoscopic assistance may be easier and safer than the
      traditional approach, especially in male patients who have a narrow pelvis. More
      data are needed in order to draw conclusions concerning oncologic results and
      before selecting the most appropriate indications for this technique.

PMID- 22874609
TI  - The effects of preoperative chemoradiotherapy on lymph node sampling in rectal
      cancer.
AB  - BACKGROUND: The current recommendation from the American Joint Committee on
      Cancer and the International Union Against Cancer is that 12 or more lymph nodes
      should be examined to appropriately stage rectal cancer. It is unclear if this
      metric is appropriate or achievable for patients who receive neoadjuvant therapy.
      OBJECTIVE: The purpose of this study was to review the effects of neoadjuvant
      chemoradiotherapy on the lymph node yield in patients with rectal cancer. DATA
      SOURCES: A comprehensive search was made of MEDLINE, PubMed, and Web of Science
      for articles published through December 2011. STUDY SELECTION: The descriptors
      rectal neoplasms, lymph nodes, lymph node yield, radiotherapy, and neoadjuvant
      therapy were used to identify articles that reported the lymph node yield with
      and without neoadjuvant chemoradiotherapy for rectal cancer. INTERVENTIONS:
      Patients received either chemoradiotherapy or no neoadjuvant treatment before
      undergoing total mesorectal excision for rectal cancer. MAIN OUTCOME MEASURES:
      The main outcome measures included the mean lymph node yield both with and
      without neoadjuvant treatment, the percentage of patients that received an
      adequate lymph node dissection, and the number of lymph nodes found to be
      positive for metastatic disease. RESULTS: A total of 7 studies were included in
      this review. They demonstrated a decrease in lymph node yield in patients who
      received neoadjuvant therapy, ranging from 7% to 53% based on the articles in
      this review. LIMITATIONS: A meta-analysis was not performed because of the
      limited complete data published on this subject. Consequently, there is
      heterogeneity in the studies that were selected for this review. CONCLUSIONS:
      Patients with rectal cancer who receive preoperative chemoradiotherapy should be
      anticipated to have a lower lymph node yield than patients who receive surgery
      alone. This calls into question if the current guideline of 12 lymph nodes is
      relevant, in particular, for those patients receiving neoadjuvant therapy.

PMID- 22874610
TI  - Immunosuppression in patients with Crohn's disease and neoplasia:  an ongoing
      clinical dilemma.

PMID- 22874611
TI  - Endoscopy-assisted minimally invasive loop ileostomy after previous restorative
      proctocolectomy.
AB  - BACKGROUND: Complications after proctocolectomy with ileal pouch-anal anastomosis
      may impair pouch function. Loop ileostomy can be performed to allow recovery of
      function before intestinal continuity is restored. To minimize operative trauma
      and to form the stoma with as little damage to the abdominal wall as possible,
      the invasiveness of the procedure should be minimized as far as possible.
      OBJECTIVE: To minimize the extent of surgical invasion, we developed a technical
      modification of loop ileostomy in which lower endoscopy is used to assist the
      procedure. PROCEDURE: The procedure requires only a single incision, which is
      made at the site of the ileostomy. While the surgeon incises the fascia and
      peritoneum, the endoscopist advances a flexible endoscope through the pouch to
      the distal part of the ileum up to approximately 40 cm above the anal verge. The
      operation lamp is switched off, allowing the surgeon to see the lighted end of
      the endoscope in a loop of the ileum near the incision. This loop is drawn out
      through the incision and the stoma is created in a standard manner. LIMITATIONS:
      Clinical factors such as the presence of adhesions or obesity limit the use of
      the procedure in certain patients. CONCLUSIONS: We believe this technique of
      endoscopic-assisted loop ileostomy is a safe method for minimizing the
      invasiveness of surgery in patients who require ileostomy after restorative
      proctocolectomy.

PMID- 22874613
TI  - Colorectal neoplasia screening before age 50? Current epidemiologic trends in the
      United States:  agency for healthcare research and quality data.

PMID- 22874614
TI  - Self-assessment quiz:  answers, critiques, and references.

PMID- 22874618
TI  - Traditional and social media coverage and charitable giving following the 2010
      earthquake in Haiti.
AB  - INTRODUCTION: Media reports on disasters may play a role in inspiring charitable
      giving to fund post-disaster recovery, but few analyses have attempted to explore
      the potential link between the intensity of media reporting and the amount of
      charitable donations made. The purposes of this study were to explore media
      coverage during the first four weeks of the 2010 earthquake in Haiti in order to
      assess changes in media-intensity, and to link this information to data on
      contributions for emergency assistance to determine the impact of media upon post
      disaster charitable giving. METHODS: Data on newspaper and newswire coverage of
      the 2010 earthquake in Haiti were gathered from the NexisLexis database, and
      traffic on Twitter and select Facebook sites was gathered from social media
      analyzers. The aggregated measure of charitable giving was gathered from the
      Center for Philanthropy at Indiana University. The intensity of media reporting
      was compared with charitable giving over time for the first month following the
      event, using regression modeling. RESULTS: Post-disaster coverage in traditional
      media and Twitter was characterized by a rapid rise in the first few days
      following the event, followed by a gradual but consistent decline over the next
      four weeks. Select Facebook sites provided more sustained coverage. Both
      traditional and new media coverage were positively correlated with donations:
      every 10% increase in Twitter messages relative to the peak percentage was
      associated with an additional US $236,540 in contributions, while each additional
      ABC News story was associated with an additional US $963,800 in contributions.
      CONCLUSIONS: While traditional and new media coverage wanes quickly after
      disaster-causing events, new and social media platforms may allow stories, and
      potentially charitable giving, to thrive for longer periods of time.

PMID- 22874619
TI  - Renin induces apoptosis in podocytes through a receptor-mediated, angiotensin II
      independent mechanism.
AB  - INTRODUCTION: Podocytes play an important role in the pathogenesis and
      progression of glomerulosclerosis. Various elements of the renin-angiotensin
      aldosterone system can induce podocyte apoptosis. However, little is known about
      the direct effects of renin on podocytes. METHODS: The authors used the mouse
      podocyte cell line to investigate the apoptotic effects mediated by the renin
      receptor. The authors used fluorescent staining and reverse-transcriptase
      polymerase chain reaction to detect renin receptor expression. Podocytes were
      incubated with renin for variable time periods. Apoptosis was evaluated by cell
      nucleus staining, and caspase-3, p38 and phospho-p38 mitogen-activated protein
      kinase (MAPK) were measured. RESULTS: The authors found that both renin receptor
      mRNA and protein were expressed in the mouse podocyte cell line. Exposure of
      podocytes to renin induced podocyte apoptosis in a time- and dose-dependent
      manner, which was accompanied by upregulation of active caspase-3 and increased
      expression of p38 MAPK. p38 MAPK phosphorylation and apoptosis were inhibited
      when the cells were pretreated with p38 MAPK inhibitor. Transfection of renin
      receptor small interfering RNA attenuated the above changes induced by renin.
      Furthermore, the effects of renin were not altered by inhibition of angiotensin
      II-mediated effects using enalaprilat or losartan. CONCLUSION: The authors
      conclude that the effects of renin are mediated through the activation of rennin
      receptor and are independent of angiotensin II generation.

PMID- 22874620
TI  - Pseudomyocardial infarction caused by expansion of colonic tube used for
      esophageal reconstruction.
AB  - Electrocardiography (ECG) is a useful tool for detecting ischemic heart disease.
      However, it has been pointed out that those ECG abnormalities resembling
      myocardial ischemia may be induced by extracardiac factors. We describe a 44-year
      old man in whom a colonic tube was used for esophageal reconstruction via the
      anterior mediastinum after esophagectomy and gastrectomy for gastrointestinal
      corrosive injury. The reconstructive tube filled with gas resulted in compression
      of the heart and caused angina-like chest pain associated with ST-segment
      elevation in lead II, III and aVF on the ECG. Coronary angiography revealed no
      stenosis of arteries. Decompression of the colonic tube by the nasogastric tube
      resulted in normalization of the ECG.

PMID- 22874621
TI  - Cytomegalovirus colitis in a human immunodeficiency virus-positive patient with a
      normal CD4 count.
AB  - Cytomegalovirus (CMV) is the most common cause of life-threatening opportunistic
      viral infection in patients with the human immunodeficiency virus (HIV) disease.
      The colon is a well-known target organ for CMV in these patients. CMV colitis is
      commonly associated with the later stages of HIV disease but rarely occurs in
      early HIV infection. In this study, an unusual case of CMV colitis in a 22-year
      old man who had a normal CD4 count but at the same time was found to be HIV
      positive with a moderately high viral load is reported.

PMID- 22874622
TI  - Effects of active smoking on airway and systemic inflammation profiles in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The markers that characterize local and systemic inflammation in
      chronic obstructive pulmonary disease (COPD) remain unclear, as do their
      correlations with smoking status and presence of disease. The aim of this study
      was to assess markers of inflammation in the peripheral blood and airways of
      current smokers without COPD, of current smokers with COPD and of ex-smokers with
      COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 +/-
      9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 +/- 15.9%), 35
      ex-smokers with COPD (mean age: 66.3 +/- 7.3 years; mean FEV1: 47.9 +/- 17.2%)
      and 20 current smokers without COPD (mean age: 49.1 +/- 6.2 years; mean FEV1:
      106.5 +/- 15.8%) were evaluated. Spirometry findings, body composition and
      serum/induced sputum concentrations of tumor necrosis factor alpha (TNF-alpha),
      interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP)
      levels, were assessed. RESULTS: Serum TNF-alpha concentration was higher in all
      current smokers than in ex-smokers with COPD. In current smokers without COPD,
      serum CRP level was lower than in ex-smokers with COPD and significantly lower
      than in current smokers with COPD. Sputum TNF-alpha concentration was higher in
      current and ex-smokers with COPD than in current smokers without COPD. Multiple
      regression analyses showed that serum TNF-alpha was associated with active
      smoking, and serum CRP and sputum TNF-alpha were associated with COPD diagnosis.
      CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients
      with COPD. Current findings also support the hypothesis that smoking and COPD
      have different effects on the regulation of airway and systemic inflammatory
      processes.

PMID- 22874623
TI  - Umbilical endometriosis.

PMID- 22874624
TI  - Performance of chromatographic systems to model soil-water sorption.
AB  - A systematic approach for evaluating the goodness of chromatographic systems to
      model the sorption of neutral organic compounds by soil from water is presented
      in this work. It is based on the examination of the three sources of error that
      determine the overall variance obtained when soil-water partition coefficients
      are correlated against chromatographic retention factors: the variance of the
      soil-water sorption data, the variance of the chromatographic data, and the
      variance attributed to the dissimilarity between the two systems. These
      contributions of variance are easily predicted through the characterization of
      the systems by the solvation parameter model. According to this method, several
      chromatographic systems besides the reference octanol-water partition system have
      been selected to test their performance in the emulation of soil-water sorption.
      The results from the experimental correlations agree with the predicted
      variances. The high-performance liquid chromatography system based on an
      immobilized artificial membrane and the micellar electrokinetic chromatography
      systems of sodium dodecylsulfate and sodium taurocholate provide the most precise
      correlation models. They have shown to predict well soil-water sorption
      coefficients of several tested herbicides. Octanol-water partitions and high
      performance liquid chromatography measurements using C18 columns are less suited
      for the estimation of soil-water partition coefficients.

PMID- 22874625
TI  - Evidence of diagnostic specificity in the neural correlates of facial affect
      processing in bipolar disorder and schizophrenia: a meta-analysis of functional
      imaging studies.
AB  - BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology
      and phenomenology but differ with regard to emotional processing. We used facial
      affect as a probe for emotional processing to determine whether there are
      diagnosis-related differences between SZ and BD in the function of the underlying
      neural circuitry. METHOD: Functional magnetic resonance imaging (fMRI) studies
      published up to 30 April 2012 investigating facial affect processing in patients
      with SZ or BD were identified through computerized and manual literature
      searches. Activation foci from 29 studies encompassing 483 healthy individuals,
      268 patients with SZ and 267 patients with BD were subjected to voxel-based
      quantitative meta-analysis using activation likelihood estimation (ALE). RESULTS:
      Compared to healthy individuals, when emotional facial stimuli were contrasted to
      neutral stimuli, patients with BD showed overactivation within the
      parahippocampus/amygdala and thalamus and reduced engagement within the
      ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed
      underactivation throughout the entire facial affect processing network and
      increased activation in visual processing regions within the cuneus. Patients
      with BD showed greater thalamic engagement compared to patients with SZ; in the
      reverse comparison, patients with SZ showed greater engagement in posterior
      associative visual cortices. CONCLUSIONS: During facial affect processing,
      patients with BD show overactivation in subcortical regions and underactivation
      in prefrontal regions of the facial affect processing network, consistent with
      the notion of reduced emotional regulation. By contrast, overactivation within
      visual processing regions coupled with reduced engagement of facial affect
      processing regions points to abnormal visual integration as the core underlying
      deficit in SZ.

PMID- 22874626
TI  - Clinical implications and validity of nursing assessments: a longitudinal measure
      of patient condition from analysis of the Electronic Medical Record.
AB  - OBJECTIVES: This study investigates risk of mortality associated with nurses'
      assessments of patients by physiological system. We hypothesise that nursing
      assessments of in-patients performed at entry correlate with in-hospital
      mortality, and those performed just before discharge correlate with postdischarge
      mortality. DESIGN: Cohort study of in-hospital and postdischarge mortality of
      patients over two 1-year periods. SETTING: An 805-bed community hospital in
      Sarasota, Florida, USA. SUBJECTS: 42 302 inpatients admitted for any reason,
      excluding obstetrics, paediatric and psychiatric patients. OUTCOME MEASURES: All
      cause mortalities and mortality OR. RESULTS: Patients whose entry nursing
      assessments, other than pain, did not meet minimum standards had significantly
      higher in-hospital mortality than patients meeting minimums; and final nursing
      assessments before discharge had large OR for postdischarge mortality. In
      hospital mortality OR were found to be: food, 7.0; neurological, 9.4;
      musculoskeletal, 6.9; safety, 5.6; psychosocial, 6.7; respiratory, 8.1; skin,
      5.2; genitourinary, 3.0; gastrointestinal, 2.3; peripheral-vascular, 3.9;
      cardiac, 2.8; and pain, 1.1. CI at 95% are within +/-20% of these values, with
      p<0.001 (except for pain). Similar results applied to postdischarge mortality.
      All results were comparable across the two 1-year periods, with 0.85 intraclass
      correlation coefficient. CONCLUSIONS: Nursing assessments are strongly correlated
      with in-hospital and postdischarge mortality. No multivariate analysis has yet
      been performed, and will be the subject of a future study, thus there may be
      confounding factors. Nonetheless, we conclude that these assessments are
      clinically meaningful and valid. Nursing assessment data, which are currently
      unused, may allow physicians to improve patient care. The mortality OR and the
      dynamic nature of nursing assessments suggest that nursing assessments are
      sensitive indicators of a patient's condition. While these conclusions must
      remain qualified, pending future multivariate analyses, nursing assessment data
      ought to be incorporated in risk-related health research, and changes in record
      keeping software are needed to make this information more accessible.

PMID- 22874627
TI  - Impact of one or two visits strategy on hypertension burden estimation in HYDY, a
      population-based cross-sectional study: implications for healthcare resource
      allocation decision making.
AB  - CONTEXT: The prevalence of hypertension in developing countries is coming closer
      to values found in developed countries. However, surveys usually rely on readings
      taken at a single visit, the option to implement the diagnosis on readings taken
      at multiple visits, being limited by costs. OBJECTIVE: To estimate more
      accurately the magnitude and extent of the resource that should be allocated to
      the prevention of hypertension. DESIGN: Population-based cross-sectional survey
      with triplicate blood pressure (BP) readings taken on two separate home-visits.
      SETTING: Rural and urban locations in three areas of Yemen (capital, inland and
      coast). PARTICIPANTS: A nationally representative sample of the Yemen population
      aged 15-69 years (5063 men and 5179 women), with an overall response rate of 92%
      in urban and 94% in rural locations. MAIN OUTCOME MEASURE: Hypertension diagnosed
      as systolic BP >=140 mm Hg and/or diastolic BP >=90 mm Hg and/or self-reported
      use of antihypertensive drugs. RESULTS: Hypertension prevalence (age-standardised
      to the WHO world population 2001) based on fulfilling the same criteria on both
      visits (11.3%; 95% Cl 10.7% to 11.9%), was 35% lower than estimation based on the
      first visit (17.3%; 16.5% to 18.0%). Advanced age, blood glucose >=7 mmol/l or
      proteinuria >=1+ at dipstick test at visit one were significant predictors of
      confirmation at visit 2. The 959 participants found to be hypertensive at visit 1
      or at visit 2 only and thus excluded from the final diagnosis had a rate of
      proteinuria (5.0%; 3.8% to 6.5%) comparable to rates of the general population
      (6.1%; 5.6% to 6.6%), and of subjects normotensive at both visits (5.6%; 5.1% to
      6.2%). Only 1.9% of Yemen population classified at high or very high
      cardiovascular (CV) risk at visit 1 moved to average, low or moderate CV risk
      categories after two visits. CONCLUSIONS: Hypertension prevalence based on
      readings obtained after two visits is 35% lower than estimation based on the
      first visit, subjects were excluded from final diagnosis belonging to low CV risk
      classes.

PMID- 22874628
TI  - The 5-minute Apgar score as a predictor of childhood cancer: a population-based
      cohort study in five million children.
AB  - OBJECTIVE: The aetiology of childhood cancer remains largely unknown but recent
      research indicates that uterine environment plays an important role. We aimed to
      examine the association between the Apgar score at 5 min after birth and the risk
      of childhood cancer. DESIGN: Nationwide population-based cohort study. SETTING:
      Nationwide register data in Denmark and Sweden. STUDY POPULATION: All live-born
      singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from
      1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of
      age. MAIN OUTCOME MEASURES: Rates and HRs for all childhood cancers and for
      specific childhood cancers. RESULTS: A total of 8087 children received a cancer
      diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9-10,
      children with a score of 0-5 had a 46% higher risk of cancer (adjusted HR 1.46,
      95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer
      risk was mostly confined to children diagnosed before 6 months of age. Children
      with an Apgar score of 0-5 had higher risks for several specific childhood
      cancers including Wilms' tumour (HR 4.33, 95% CI 2.42 to 7.73). CONCLUSIONS: A
      low 5 min Apgar score was associated with a higher risk of childhood cancers
      diagnosed shortly after birth. Our data suggest that environmental factors
      operating before or during delivery may play a role on the development of several
      specific childhood cancers.

PMID- 22874629
TI  - Implementation of a low-budget, lifestyle-improvement method in an ordinary
      primary healthcare setting: a stepwise intervention study.
AB  - OBJECTIVE: To evaluate, in an ordinary primary healthcare setting, the effects of
      a screening questionnaire and a self-administered health profile dealing with
      special reference to the involvement of motivated individuals in need of
      lifestyle changes. DESIGN: Intervention study in a naturalistic context, using a
      screening questionnaire offered to consecutive patients, followed by a self
      administered health profile and a health dialogue. SETTING: Hisingen primary
      healthcare area (130 033 inhabitants), Gothenburg, Sweden. PARTICIPANTS: Men and
      women aged between 18 and 79, visiting any of the eight public primary healthcare
      centres (PCC) during an 8-month period, were presented with a screening
      questionnaire and, were offered, a health profile, a plasma glucose (p-glucose),
      blood pressure check and a health dialogue. MAIN OUTCOME MEASURES: Motivation
      level, negative lifestyle factors in screening questionnaire and intraindividual
      changes in blood pressure, p-glucose, body mass index (BMI) and lifestyle factors
      between baseline and 1-year follow-up. RESULTS: Subjects with less favourable
      lifestyle and higher motivation chose to participate. A higher percentage of
      presumptive participants reported a less favourable lifestyle. The presumptive
      participants also indicated higher motivation. Participants showed more readiness
      to initiate lifestyle changes compared to non-participants (p<0.001). At 1-year
      follow-up significant reductions in BMI, waist circumference, waist-hip ratio
      (WHR), blood pressure and p-glucose were observed. CONCLUSIONS: The results
      indicate that the method is on target and applicable to motivated individuals
      with a 'risk profile'. A pedagogical model including a self-administered health
      profile and a health dialogue, combined with emphasising the individual's own
      resources, seems to be a feasible method for effective preventive work in primary
      healthcare.

PMID- 22874630
TI  - Case stories in general practice: a focus group study.
AB  - OBJECTIVES: To explore the interactive process of sharing case stories in small
      group activity in general practice. DESIGN: Qualitative focus group study.
      SETTING: Peer-group meetings of doctors attending specialist training or
      continuous medical education in general practice. PARTICIPANTS: Twenty female and
      30 male doctors working in general practice in Norway. RESULTS: The storyline of
      case presentations included detailed stories with emotional engagement, co
      authored by other group members. The stories initiated discussions and
      reflections concerning patients' and doctors' perspectives, medical ethics as
      well as clinical problems. The safe atmosphere allowed testing out boundaries of
      socially shared knowledge. CONCLUSIONS: Sharing case stories in small groups in
      general practice initiated interaction that facilitated meaning-making,
      reflection and peer support.

PMID- 22874631
TI  - Dyslipidaemia in HIV-1-infected patients receiving protease inhibitors after
      initial treatment with first-line-based non-nucleoside reverse transcriptase
      inhibitors: a cross-sectional study.
AB  - OBJECTIVES: Lipid abnormalities associated with antiretroviral therapy in people
      with HIV infection are more frequent with protease inhibitors (PI)-based
      regimens. Whether effects extend to patients receiving a PI subsequent to failure
      on non-nucleoside reverse-transcriptase inhibitors (NNRTI)-based regimen is still
      unknown. We investigated the effects of secondary treatment with a PI on the
      lipid profile in a group of patients with HIV infection in Cameroon. DESIGN: This
      was a cross-sectional study. SETTING: This study was carried out at the
      registered centre for HIV treatment of the Yaounde Jamot Hospital in Cameroon.
      PARTICIPANTS: Participants were consecutively recruited between November 2009 and
      January 2010. There were 138 HIV-1 patients on initial treatment with an NNRTI
      regimen and 66 HIV patients on secondary treatment with a PI for at least 12
      months. Lipid abnormalities were based on the National Cholesterol Education
      Program, Adult Treatment Panel III criteria. OUTCOME MEASURES: Levels of lipid
      parameters among patients on PI and NNRTI. RESULTS: Median (IQR) levels (mg/dl),
      NNRTI-treated versus PI-treated patients were 185 (149-225) and 189 (147-244) for
      total cholesterol, 46 (27-66) and 42 (28-82) for high-density lipoprotein (HDL)
      cholesterol, 121 (90-169) and 126.9 (71-176) for low-density lipoprotein (LDL)
      cholesterol, 134 (98-174) and 138 (111-167) for triglycerides, and 4.3 (2.9-6.2)
      and 5.1 (2.6-7.9) for total/HDL-cholesterol ratio (all p>0.32). The most frequent
      lipid abnormality in the two groups was high LDL-cholesterol (46.4% (NNRTI) vs
      54.5% (PI)). The occurrence of lipid abnormalities was similar in the two groups
      (all p>0.29). CONCLUSIONS: The use of PI does not appear to deteriorate the lipid
      profile of HIV patients above and beyond abnormalities induced by an unsuccessful
      initial treatment with NNRTI. Monitoring of lipid profile during HIV treatment
      regardless of the regimens would improve timely detection and management of
      abnormalities, to mitigate related risks.

PMID- 22874632
TI  - The impact of psychogenic stressors on oxidative stress markers and patterns of
      CYP2E1 expression in mice liver.
AB  - The increasing number of psychogenic stressors is a side effect of civilization.
      It results in the development of psychoemotional stresses and psychosomatic
      diseases. In this study we evaluated the effect of the chronic psychoemotional
      stress on the level of CYP2E1 expression in the liver of C57Bl/6 mice. Stress was
      induced by the immobilization of animals for 4h per day during 7 or 14 days.
      CYP2E1 expression level was evaluated on the 7th and 14th days of the experiment,
      respectively. We detected a twofold reduction in CYP2E1 protein expression level
      relatively to controls for both time points tested. This reduction was no longer
      significant when the effect of the stressor factor was terminated on the 14th day
      of the experiment and animals were analyzed one week later. Remarkably Cyp2e1
      mRNA expression level was constant at any time point of the experiment. We also
      documented significant changes in the expression/activity of two oxidative stress
      markers examined in the liver of treated mice. The catalase activity decreased
      fivefold while malondialdehyde transiently increased threefold. These data
      suggest that oxidative stress can be involved in the reduction of hepatic CYP2E1
      and catalase activity under the conditions of chronic emotional stress.

PMID- 22874633
TI  - Multidimensionality of the Zarit Burden Interview across the severity spectrum of
      cognitive impairment: an Asian perspective.
AB  - BACKGROUND: We aimed to examine the multidimensionality of the Zarit Burden
      Interview (ZBI) beyond the conventional dual-factor structure among caregivers of
      persons with cognitive impairment in a predominantly Chinese multiethnic Asian
      population, and ascertain how these dimensions vary across the spectrum of
      disease severity. METHODS: We studied 130 consecutive dyads of primary caregivers
      and patients attending a memory clinic over a six-month period. Caregiver burden
      was measured by the 22-item ZBI, and disease severity was staged via the Clinical
      Dementia Rating (CDR) scale. We performed principal component analysis (PCA) with
      varimax rotation to determine the factor structure of the ZBI. The magnitude of
      burden in each factor was expressed as the item to total ratio (ITR) and plotted
      against the stages of cognitive impairment. Descriptive and inferential
      statistics were applied to study the relationships between dimensions with
      disease and caregiver characteristics. RESULTS: We identified four factors:
      demands of care and social impact, control over the situation, psychological
      impact, and worry about caregiving performance. ITRs of the first three factors
      increased with severity of disease and were related to recipients' functional
      status and disease characteristics. ITR in the dimension of worry about
      performance was endorsed highest across the spectrum of disease severity,
      starting as early as the stage of mild cognitive impairment and peaking at CDR 1.
      CONCLUSION: Multidimensionality of ZBI was confirmed in our local setting. Each
      dimension of burden was unique and expressed differentially across disease
      severity. The dimension of worry about performance merits further study.

PMID- 22874634
TI  - Relative validity of a 3 d estimated food record in German toddlers.
AB  - OBJECTIVE: To determine the relative validity of a 3 d estimated food record
      (EFR) used to assess energy and nutrient intakes in toddlers, using a 3 d weighed
      food record (WDR) as the reference method. DESIGN: Parents reported the food and
      beverage intakes of their children using an EFR concurrently with a WDR over
      three consecutive days. Estimation of mean differences, Spearman correlation
      coefficients, cross-classifications and Bland-Altman plots were used to assess
      the agreement between the intakes of energy and fourteen nutrients obtained from
      the EFR and the WDR. SETTING: Data obtained from a representative sample of
      infants or toddlers in Germany. SUBJECTS: Sixty-seven toddlers aged 10-36 months
      who had completed an EFR for a 3 d recording period that corresponded to the WDR
      were included in the present analysis. RESULTS: Energy and nutrient intakes did
      not differ between the EFR and the WDR, except for linoleic acid and retinol. For
      all dietary intakes, Spearman rank correlation coefficients between the EFR and
      the WDR ranged from 0.35 to 0.80 (P <= 0.004). The proportion of participants
      correctly classified into quartiles ranged from 75 % for ascorbic acid intake to
      96 % for Fe intake, and the percentage of misclassification was 9 % or less. The
      weighed kappa values ranking the participants ranged from 0.23 for ascorbic acid
      intake to 0.59 for Fe intake. The Bland-Altman plots indicated a good agreement
      for all dietary intakes estimated from the EFR. CONCLUSIONS: Our study suggests
      that this EFR is a valid assessment instrument for estimating the energy and
      nutrient intakes among toddlers at the group level.

PMID- 22874635
TI  - Exposure to environmental enrichment prior to a cerebral cortex stab wound
      attenuates the postlesional astroglia response in rats.
AB  - Modulation of astroglial components involved in reactive postlesional responses
      in the rat cerebral cortex was analyzed following exposure to environmental
      enrichment (EE) condition prior to injury. For this purpose, changes in %
      immunoreactive (IR) area of GFAP, vimentin, EAAT1 and ezrin were evaluated in the
      perilesional zone after placing a cortical stab wound in the visual cerebral
      cortex of adult rats. GFAP-IR postlesional reactive astrocytosis in the
      perilesional cortex was significantly lower in the animal group exposed to EE
      during postnatal development. This GFAP-IR reaction seems to be associated with
      existing astroglia, because neither BrdU- nor endogenous Ki-67-labeled nuclei
      were found in the perilesional cortex analyzed. Increased ezrin-IR area in the
      visual cortex of rats exposed to EE condition suggests the formation of new
      synapses or the enhancement of astroglial involvement in the existing ones. No
      effects of EE were found on either EAAT1- or vimentin-IR area. Results suggest
      that exposure to EE conditions prior to injury attenuates the postlesional
      astroglia GFAP-response in the perilesional cortex of rats. Whether this
      attenuated postlesional astroglia GFAP-response promotes or not protective
      effects on the cortical neuropil remains to be explored in futures studies.

PMID- 22874636
TI  - Breast reconstruction in the high risk patient with systemic connective tissue
      disease: a case series.
AB  - INTRODUCTION: The presence of severe underlying connective tissue disease may
      restrict the reconstructive options offered to a woman in the event of
      mastectomy. Putative concerns about reconstructive surgery include the effects of
      connective tissue disease and immunosuppression on wound healing and donor site
      morbidity, and increased risks of deranged clotting and thrombophilia after free
      tissue transfer. There is also the possibility of an unpredictable tissue
      reaction after oncological resection surgery and adjuvant radiotherapy.
      METHODOLOGY: Here we present a review of the current sparse evidence regarding
      reconstructive breast surgery in this challenging group of patients. In addition
      we present a series of six consecutive patients with a spectrum of connective
      tissue disorders including combinations of longstanding Systemic Lupus
      Erythematosis (SLE), Rheumatoid arthritis and Raynaud's Disease who underwent
      successful post-mastectomy reconstruction with an extended autologous latissimus
      dorsi flap, along with subsequent successful correction of asymmetry and/or
      nipple reconstruction. RESULTS: There is a paucity of literature on this subject
      perhaps suggesting that surgeons are reluctant to offer reconstruction or that
      uptake is poor in this group. Complications related to radiotherapy and free
      tissue transfer in patients with severe CTD is less than may be expected. The
      most common complications experienced by our patients with CTD after extended ALD
      breast reconstruction were persistent donor site seroma, wound dehiscence and
      delayed haematoma formation, reflecting the abnormal inflammatory response and
      deranged haemostatic cascade common to connective tissue disease. However, all
      six patients made a full recovery from surgery without residual donor site
      morbidity and with an acceptable aesthetic breast reconstruction. CONCLUSION:
      Careful peri-operative management is crucial in this group of patients, but good
      outcomes are possible using a variety of reconstructive techniques. This is the
      first reported series of patients with severe connective tissue disease who have
      been managed with extended ALD breast reconstruction. The majority of
      complications relate to the donor site but the favourable outcomes demonstrate
      that the extended ALD flap remains a reliable reconstructive option for this
      group.

PMID- 22874637
TI  - Pb (II) removal from aqueous media by EDTA-modified mesoporous silica SBA-15.
AB  - An organic-inorganic hybrid mesoporous silica material was synthesized by two
      step post-grafting method of SBA-15 with 3-aminopropyltrimethoxy-silane (APTES)
      and thionyl dichloride (SOCl(2)) activated ethylenediaminetetraacetic acid (EDTA)
      in sequence and measured by means of Fourier transform infrared spectroscopy (FT
      IR), X-ray diffraction (XRD), elemental analysis (EA), transmission electron
      microscopy (TEM), nitrogen (N(2)) adsorption-desorption analysis and back
      titration. The material was found having the beneficial properties of mesoporous
      silica SBA-15 and EDTA. Adsorption potential of the material for Pb (II) removal
      from aqueous solution was investigated by varying experimental conditions such as
      pH, contact time and initial metal concentration. The removal efficiency of
      Pb(2+) was high under studied experimental conditions. The adsorption equilibrium
      could be reached within 20 min and the kinetic data were fitted well by pseudo
      second-order and intraparticle diffusion model. The adsorbent exhibited a
      favorable performance and its maximum adsorption capacity calculated by the
      Langmuir model was 273.2 mg g(-1). Recycling experiments showed the adsorbent
      could be regenerated by acid treatment without altering its properties. The
      chemical states of the elements involved in the adsorption were analyzed by X-ray
      photoelectron spectroscopy (XPS). The results demonstrated that the adsorption
      mechanism of the material involved Na Pb ion-exchange and carboxyl group
      dominated surface complexation.

PMID- 22874638
TI  - Calculation of the surface potential and surface charge density by measurement of
      the three-phase contact angle.
AB  - The silica/silicon wafer is widely used in the semiconductor industry in the
      manufacture of electronic devices, so it is essential to understand its physical
      chemistry and determine the surface potential at the silica wafer/water
      interface. However, it is difficult to measure the surface potential of a
      silica/silicon wafer directly due to its high electric resistance. In the present
      study, the three-phase contact angle (TPCA) on silica is measured as a function
      of the pH. The surface potential and surface charge density at the silica/water
      surface are calculated by a model based on the Young-Lippmann equation in
      conjunction with the Gouy-Chapman model for the electric double layer. In
      measurements of the TPCA on silica, two distinct regions were identified with a
      boundary at pH 9.5-showing a dominance of the surface ionization of silanol
      groups below pH 9.5 and a dominance of the dissolution of silica into the aqueous
      solution above pH 9.5. Since the surface chemistry changes above pH 9.5, the
      model is applied to solutions below pH 9.5 (ionization dominant) for the
      calculation of the surface potential and surface charge density at the
      silica/aqueous interface. In order to evaluate the model, a galvanic mica cell
      was made of a mica sheet and the surface potential was measured directly at the
      mica/water interface. The model results are also validated by experimental data
      from the literature, as well as the results obtained by the potentiometric
      titration method and the electro-kinetic measurements.

PMID- 22874639
TI  - Kinetics of polydopamine film deposition as a function of pH and dopamine
      concentration: insights in the polydopamine deposition mechanism.
AB  - The formation of "polydopamine" thin films becomes a popular method to confer
      multifunctionality to solid-liquid interfaces through the available catechol
      groups of such films. The mechanism of film formation is, however, not well
      elucidated, and most investigators use the protocol developed by Messersmith et
      al. (H. Lee, S.M. Dellatore, W.M. Miller, P.B. Messersmith, Science 318 (2007)
      426.) using a dopamine solution at a constant concentration of 2 g L(-1) in the
      presence of Tris(hydroxymethyl aminomethane) at pH 8.5. A particular finding of
      this initial study was that the film thickness reaches a constant value (almost
      substrate independent) of about 40 nm. Herein, we investigate the change in the
      polydopamine film thickness, morphology, surface energy and electrochemical
      properties as a function of the concentration of the dopamine solution put in the
      presence of silicon substrates. As a surprising finding, we observe a constant
      increase in the maximal film thickness with an increase in the dopamine solution
      between 0.1 and 5 g L(-1). The surface morphology is also markedly affected by
      the concentration of the dopamine solution, whereas the different components of
      the surface energy stay unaffected by the dopamine solution concentration. In
      addition, electrochemical impedance spectroscopy shows that the higher the
      initial dopamine concentration, the more rapidly compact and impermeable films
      are formed. Finally, we propose a model for the deposition of polydopamine films
      taking all our findings into account. This model relies on a rate equation taking
      into account both attractive and repulsive interactions between small
      polydopamine aggregates on the surface and in solution.

PMID- 22874640
TI  - Alternative cleavage and polyadenylation during colorectal cancer development.
AB  - PURPOSE: Alternative cleavage and polyadenylation (APA) of mRNAs is a phenomenon
      that alters 3'-untranslated region length leading to altered posttranscriptional
      regulation of gene expression. Changing APA patterns have been shown to result in
      misregulation of genes involved in carcinogenesis; therefore, we hypothesized
      that altered APA contributes to progression of colorectal cancer, and that
      measurement of APA may lead to discovery of novel biomarkers. EXPERIMENTAL
      DESIGN: We used next-generation sequencing to directly measure global patterns of
      APA changes during colorectal carcinoma progression in 15 human patient samples.
      Results were validated in a larger cohort of 50 patients, including 5
      normal/carcinoma pairs from individuals. RESULTS: We discovered numerous genes
      presenting progressive changes in APA. Genes undergoing untranslated region
      (3'UTR) shortening were enriched for functional groups such as cell-cycle and
      nucleic acid-binding and processing factors, and those undergoing 3'UTR
      lengthening or alternative 3'UTR usage were enriched for categories such as cell
      cell adhesion and extracellular matrix. We found indications that APA changes
      result from differential processing of transcripts because of increased
      expression of cleavage and polyadenylation factors. Quantitative PCR analysis in
      a larger series of human patient samples, including matched pairs, confirmed APA
      changes in DMKN, PDXK, and PPIE genes. CONCLUSIONS: Our results suggest that
      genes undergoing altered APA during human cancer progression may be useful novel
      biomarkers and potentially targeted for disease prevention and treatment. We
      propose that the strategy presented here may be broadly useful in discovery of
      novel biomarkers for other types of cancer and human disease.

PMID- 22874641
TI  - Comparison of the incorporation of orally administered DHA into plasma,
      erythrocyte and cheek cell glycerophospholipids.
AB  - Adequate intake of n-3 fatty acids plays an important role in human health. The
      analysis of various blood lipids is used as a measure of fatty acid status in
      humans. Cheek cell phospholipids (PL) have also been proposed as biological
      markers, but are rarely used in clinical studies due to limitations in sample
      quality and quantity. An improved method for the analysis of cheek cell
      glycerophospholipid fatty acids is applied in a 29 d supplementation trial with
      510 mg DHA daily. The DHA increases in cheek cell, plasma and erythrocyte
      glycerophospholipids are compared. High correlations are shown for
      glycerophospholipid DHA between cheek cells and plasma (r 0.88) and erythrocytes
      (r 0.76) before study commencement. After the daily supplementation of DHA, the
      half-maximal glycerophospholipid DHA level is reached after about 4 d in plasma,
      6 d in erythrocytes and 10 d in cheek cells. The mean DHA increase (mol%)
      relative to baseline was most prominent in plasma (186 %), followed by cheek
      cells (180 %) and erythrocytes (130 %). Considering a lag phase of about 5 d,
      cheek cells reflect short-term changes in dietary fat uptake. Based on the data
      of the present study, they can be used alternatively to plasma and erythrocyte PL
      as non-invasive n-3 fatty acid status markers.

PMID- 22874642
TI  - Interpretation of bafilomycin, pH neutralizing or protease inhibitor treatments
      in autophagic flux experiments: novel considerations.
AB  - Recent publications showed that the kinase MTOR localizes to lysosomes and its
      activation depends on amino acids inside the lysosomal lumen, implying that
      autophagic protein degradation is a positive regulator of MTOR in this setting.
      Since decreased MTOR activity results in autophagy induction, drug treatments
      that block autolysosomal degradation (a commonly used technique to estimate
      autophagic flux) may actually interfere not only with lysosomal breakdown, but
      also increase autophagosome generation through impaired MTOR signaling.

PMID- 22874643
TI  - Perceptual effects of noise reduction with respect to personal preference, speech
      intelligibility, and listening effort.
AB  - OBJECTIVES: Most modern hearing aids use noise reduction to increase listening
      comfort in noisy environments. However, it is unclear whether perceptual effects
      (e.g., intelligibility, listening effort, and preference) of noise reduction
      differ among hearing aids and among listeners. The authors compared perceptual
      scores across different hearing aid noise-reduction systems to determine (1)
      whether noise-reduction systems differ perceptually and (2) which factors
      underlie the overall preference of individual listeners. DESIGN: The authors
      recorded hearing aid noise-reduction outputs and used these signals in a
      laboratory experiment. The recording method allowed the evaluation of noise
      reduction in an isolated form, without the dominant effects of hearing aid
      frequency response and interactions with dynamic-range compression. Ten normal
      hearing subjects listened to speech in babble noise processed by noise reduction
      from four different hearing aids. The subjects performed (1) speech
      intelligibility tests, (2) listening-effort ratings, and (3) paired-comparison
      ratings with respect to noise annoyance, speech naturalness, and overall
      preference. RESULTS: Noise-reduction systems from different hearing aids differed
      in the degree to which they influenced the noise annoyance and speech naturalness
      perceived by the normal-hearing listeners. Small differences in intelligibility
      and effort scores were found among different noise-reduction systems but not
      between having noise reduction on and off. Subjects differed in whether their
      overall preference was more strongly related to noise annoyance or to speech
      naturalness. CONCLUSIONS: The authors conclude that noise annoyance and speech
      naturalness are determining factors for the overall preference of normal-hearing
      listeners for a specific noise-reduction condition, and found individual
      differences in the preferred weighting of these factors even in a homogeneous
      group of normal-hearing listeners. Subsequent experiments should include hearing
      impaired subjects to determine whether these conclusions also hold for a more
      heterogeneous group of listeners. If these results can be extrapolated to hearing
      impaired listeners, the fitting and fine-tuning of noise reduction in hearing
      aids needs considerable revision.

PMID- 22874644
TI  - A new auditory threshold estimation technique for low frequencies:  proof of
      concept.
AB  - OBJECTIVES: Presently available nonbehavioral methods to estimate auditory
      thresholds perform less well at frequencies below 1 kHz than at 1 kHz and above.
      For many uses, such as providing accurate infant hearing aid amplification for
      low-frequency vowels, an accurate nonbehavioral method to estimate low-frequency
      thresholds is needed. A novel technique was developed to estimate low-frequency
      cochlear thresholds based on the use of a previously reported waveform. It was
      determined how well the method worked by comparing the resulting thresholds to
      thresholds from onset-response compound action potentials (CAPs) and single
      auditory-nerve (AN)- fibers in cats. A long-term goal is to translate this
      technique for use in humans. DESIGN: An electrode near the cochlea records a
      combination of cochlear microphonic (CM) and neural responses. In response to low
      frequency, near threshold-level tones, the CM is almost sinusoidal whereas the
      neural responses occur preferentially at one phase of the tone. If the tone is
      presented again but with its polarity reversed, the neural response keeps the
      same shape, but shifts 1/2 cycle in time. Averaging responses to tones presented
      separately at opposite polarities overlaps and interleaves the neural responses
      and yields a waveform in which the CM is canceled and the neural response appears
      twice each tone cycle, that is, the resulting neural response is mostly at twice
      the tone frequency. The resultant waveform is referred to as "the auditory nerve
      overlapped waveform" (ANOW). In this study, ANOW level functions were measured in
      anesthetized cats from 10 to 80 dB SPL in 10 dB steps using tones between 0.3 and
      1 kHz. As a response metric, the magnitude of the ANOW component was calculated
      at twice the tone frequency (ANOW2f). The ANOW threshold was the sound level
      where the interpolated ANOW2f crossed a statistical criterion that was higher
      than 95% of the noise floor distribution. ANOW thresholds were compared with
      onset-CAP thresholds from the same recordings and single-AN-fiber thresholds from
      the same animals. RESULTS: ANOW and onset-CAP level functions were obtained for
      0.3 to 1 kHz tones, and single-AN-fiber responses from cats. Except at 1 kHz,
      typical ANOW thresholds were mostly 10 to 20 dB more sensitive than onset-CAP
      thresholds and 10 to 20 dB less sensitive than the most sensitive single-AN-fiber
      thresholds. CONCLUSIONS: ANOW provides frequency-specific estimates of cochlear
      neural thresholds over a frequency range that is important for hearing but is not
      well accessed by nonbehavioral, objective methods. Results suggest that with
      further targeted development, the ANOW low-frequency threshold estimation
      technique can be useful both clinically in humans and in basic-science animal
      experiments.

PMID- 22874645
TI  - Colchicine toxicity in end-stage renal disease patients: a case-control study.
AB  - Colchicine has been used in a number of disorders. Because colchicine is
      partially excreted from the kidney, there is a need for dose reduction in case of
      renal functional impairment. There are no data with regards to safe dosing
      schedule of colchicine in hemodialysis patients. We aimed to evaluate adverse
      effects of colchicine use in a hemodialysis cohort. We screened hemodialysis
      patients who were using colchicine for any reason. All patients were interviewed
      regarding possible toxicities of colchicine use and were examined with a special
      focus on neuromuscular system. Creatine kinase and myoglobin were used to detect
      any subclinical muscle injury or rhabdomyolysis, respectively. Twenty-two
      maintenance hemodialysis patients who were on colchicine for more than 6 months
      and 20 control hemodialysis patients not using colchicine were included in the
      study. Four of 22 patients were using 0.5 mg/day, 4 patients were using 1.5
      mg/day, and 14 patients were using 1 mg/day colchicine. Mean duration for
      colchicine use was 8.9+/-8.2 years. There was no difference between the groups in
      terms of myoneuropathic signs and symptoms and blood counts except for white
      blood cell count, which was significantly higher in patients on colchicine. Serum
      creatine kinase (56.3+/-39.5 and 52.1+/-36.1 for colchicine and control groups,
      respectively, P=0.72) and myoglobin (191.4+/-108.8 and 214.6+/-83.5 for
      colchicine and control groups, respectively, P=0.44) levels were not different
      between the groups. We conclude that in a small number of haemodialysis patients
      who were apparently tolerating colchicine, detailed assessment revealed no
      evidence of sublinical toxicity when compared with controls.

PMID- 22874646
TI  - Cognitive behavioural therapy for unusual experiences in children: a case series.
AB  - BACKGROUND: Over half of children in the general population report unusual or
      "psychotic-like" experiences (PLEs). The development of a later at-risk mental
      state is associated with persistent, distressing, PLEs, which are appraised
      negatively and hard to cope with. We have designed a novel, manualized, cognitive
      behavioural intervention for children aged 9 to 14 years, which aims to reduce
      emotional problems, improve coping and resilience, and help children manage PLEs,
      before an identifiable psychosis risk develops. We report on the feasibility,
      acceptability and clinical impact of the intervention. METHOD: Four children who
      reported PLEs and emotional problems in a community survey completed the
      intervention, and gave detailed feedback. Clinical outcomes were assessed before,
      during, and after therapy. RESULTS: Emotional problems, PLE frequency, and PLE
      impact all decreased during the intervention. Child and therapist satisfaction
      with the treatment was high. CONCLUSIONS: It is feasible, acceptable and helpful
      to offer psychological interventions to children who report emotional distress
      and PLEs, prior to the emergence of clear risk factors. Our intervention has the
      potential to increase resilience to the development of future mental health
      problems. A larger, randomized controlled evaluation is underway.

PMID- 22874647
TI  - Effects of unconjugated bilirubin on chromosomal damage in individuals with
      Gilbert's syndrome measured with the micronucleus cytome assay.
AB  - Circulating unconjugated bilirubin (UCB) has been reported to protect against
      lung and colorectal cancer. The present study aimed to explore, for the first
      time, whether mildly elevated circulating UCB, as found in Gilbert's syndrome
      (GS), is associated with changes of DNA damage. A random 76 individuals, matched
      for age and gender, were recruited from the general population and allocated into
      the GS group (UCB >= 17.1 uM; n = 38) or control group (UCB <17.1 uM; n = 38).
      Chromosomal and cytological changes were determined in lymphocytes and buccal
      cells using the cytokinesis-block micronucleus cytome assay (CBMN) and buccal
      micronucleus cytome assay (BMcyt). No significant differences were found between
      GS subjects and the control group in the CBMN and BMcyt determined endpoints.
      Subsequently, when age dependency of effects were analysed, lower formation of
      buccal micronucleated cells (by 73.3%) and buccal nuclear buds (by 70.9%) in the
      GS subgroup >= 30 years were found, compared to the GS subgroup <30 years. These
      findings suggest DNA protection in epithelial tissue of older individuals with
      GS.

PMID- 22874648
TI  - Perception of audio-visual speech synchrony in Spanish-speaking children with and
      without specific language impairment.
AB  - Speech perception involves the integration of auditory and visual articulatory
      information, and thus requires the perception of temporal synchrony between this
      information. There is evidence that children with specific language impairment
      (SLI) have difficulty with auditory speech perception but it is not known if this
      is also true for the integration of auditory and visual speech. Twenty Spanish
      speaking children with SLI, twenty typically developing age-matched Spanish
      speaking children, and twenty Spanish-speaking children matched for MLU-w
      participated in an eye-tracking study to investigate the perception of
      audiovisual speech synchrony. Results revealed that children with typical
      language development perceived an audiovisual asynchrony of 666 ms regardless of
      whether the auditory or visual speech attribute led the other one. Children with
      SLI only detected the 666 ms asynchrony when the auditory component preceded
      [corrected] the visual component. None of the groups perceived an audiovisual
      asynchrony of 366 ms. These results suggest that the difficulty of speech
      processing by children with SLI would also involve difficulties in integrating
      auditory and visual aspects of speech perception.

PMID- 22874649
TI  - Revisiting the anatomy and biomechanics of the anconeus muscle and its role in
      elbow stability.
AB  - BACKGROUND: Recent studies have designated the anconeus muscle as an option for
      use as a pedicled flap for covering soft tissue defects about the elbow, with
      reported minimal risk of morbidity. This has raised the question as to the
      importance of the anconeus muscle and as to whether this is truly an accessory
      muscle that can be sacrificed, or whether the anconeus muscle significantly
      contributes to elbow and forearm stability? This study revisits the anatomy and
      biomechanics of the anconeus muscle and aims to investigate the neuromuscular
      compartments of the anconeus muscle and to determine the changes in the muscle
      length, fibre length and moment arm over a range of elbow flexion angles for each
      compartment. METHODS: An anatomical study on 8 human cadavers (51-77 years of
      age) was done and a 2-dimensional kinematic elbow model developed to determine
      changes in the muscle length and moment arm of the muscle related to changes in
      elbow flexion angles. FINDINGS: The muscle was modelled with two possible lines
      of action, one along the posterior and another on the anterior edge of the muscle
      as they had different muscle fibre lengths (posterior: average of 32 mm,
      anterior: average of 20 mm). The anterior edge also had an aponeurosis which was
      70% of its length. From 0 to 120 degrees  elbow flexion, the length of the
      posterior and anterior edges increased with a maximum change recorded at 90
      degrees  elbow flexion (31.7+/-1.0 mm and 65.3+/-1.4 mm, respectively). The
      moment arm is 14-mm at 0 degrees  flexion, but between the posterior and anterior
      edges it decreases at different rates with increasing elbow flexion angle. Beyond
      80 degrees , the anterior edge behaves as an elbow flexor, while the posterior
      edge remains an elbow extensor. The study demonstrates that the anconeus muscle
      has two neuromuscular compartments each with distinct intramuscular innervations
      and muscle fibre lengths. INTERPRETATION: The posterior and deep aspect of the
      muscle functions as an elbow extensor decreasing in influence with increasing
      elbow flexion angle. The anterior superficial aspect which is adjacent and
      parallel to the lateral collateral ligaments, would most likely work in unison to
      provide constraint to the posterolateral stability of the elbow.

PMID- 22874650
TI  - Diagnosis and disclosure of a memory problem is associated with quality of life
      in community based older Australians with dementia.
AB  - BACKGROUND: Identification of factors associated with quality of life (QoL) in
      people having dementia will help develop strategies for maintenance and
      improvement of patient QoL. This study examined the predictors of QoL in a
      community-dwelling population aged 75 years and over, with or without dementia.
      METHODS: This was a cross-sectional study involving 169 GPs and 2,028 patients.
      Patients were interviewed to collect information on personal circumstances.
      Several instruments were administered including the WHOQOL-BREF (quality of life
      outcome measure), Geriatric Depression Scale, GPAQ (satisfaction with GP care),
      and the CAMCOG-R (cognitive function). Patients with a CAMCOG-R score < 80 were
      allocated to the dementia group. GPs provided an independent clinical judgment of
      cognitive function for each of their participating patients. RESULTS: The
      dementia group had significantly lower QoL scores in all four domains of the
      WHOQOL-BREF (all p <= 0.002). The GDS score was negatively correlated with all
      four domains in the non-dementia group and with physical, psychological, and
      environmental QoL in the dementia group (all p < 0.001). Satisfaction with GP
      communication was positively associated with psychological QoL in the dementia
      group and all domains in the non-dementia group. Participants in the dementia
      group who had been given a diagnosis of a memory problem had significantly higher
      physical (2.05, 95% CI 0.36 to 3.74) and environmental (2.18, 95% CI 0.72 to
      3.64) QoL. CONCLUSIONS: Satisfaction with GP communication is associated with a
      higher QoL in their older patients. Diagnosis and disclosure of memory problems
      is associated with better QoL in people with dementia. Clinicians should not be
      deterred from discussing a memory diagnosis and plans for the future with
      patients.

PMID- 22874651
TI  - Survey of airway management strategies and experience of non-consultant doctors
      in intensive care units in the UK.
AB  - BACKGROUND: Airway problems continue to occur in intensive care setting.
      Management strategies, staffing, and availability of equipment can all have an
      influence. METHODS: We undertook a standardized telephone survey of airway
      management strategies, staffing, and airway equipment availability in general
      intensive care units (ICUs) in the UK, before the reporting of the Fourth
      National Audit Project of the Royal College of Anaesthetists and Difficult Airway
      Society. RESULTS: All 257 UK general ICUs were contacted and 77% replied. At the
      time of the survey, 6.3% of all ICU patients were judged by respondents to have
      an increased risk of airway complications. While 38% of respondents reported
      using individualized airway management plans for patients with higher risk
      airways, only 19% of the patients identified as 'at risk' had such a plan in
      place. Action plans for the management of unanticipated tracheal tube and
      tracheostomy displacement were available in 7% and 10% of ICUs, respectively,
      although 27% of respondents reported no training in recognition and management of
      these events. Few respondents could describe the equipment available for
      emergency transtracheal access on their ICU and 13% had no training in its use.
      More than half of the respondents (56%) routinely used continuous waveform
      capnography for patients with artificial airways. A fibrescope was available to
      all ICUs: immediately in 63% and after >5 min in 14%. In 33% of ICUs, the most
      junior doctor providing out-of-hours cover had not always obtained the Royal
      College of Anaesthetists initial assessment of competency in anaesthesia. One
      third of ICU residents also had commitments outside the ICU. An additional
      anaesthetist for managing airway emergencies was available in all ICUs with 80%
      being on-site. CONCLUSIONS: There remains room for improvement in airway
      management strategies and resources in ICUs in the UK.

PMID- 22874653
TI  - A school-based supplementary food programme in rural Kenya did not reduce
      children's intake at home.
AB  - OBJECTIVE: To examine changes in energy intake along with markers of dietary
      quality (animal-source energy and protein intakes) among household members in the
      presence of supplementary school feeding in rural Kenya. DESIGN: A 2-year,
      longitudinal, randomized controlled feeding intervention study. SETTING: Kyeni
      South Division, Embu District, Kenya. SUBJECTS: A total of 182 schoolchildren and
      selected household members. RESULTS: There was no evidence that schoolchildren
      who received supplementary snacks at school experienced reduced intakes at home
      or that intakes by other family members were increased at the expense of the
      schoolchild's intake. CONCLUSIONS: This analysis highlights a number of factors
      useful in planning for supplementary feeding interventions in rural Kenya and
      similar communities.

PMID- 22874652
TI  - Characterization of three novel mechanosensitive channel activities in
      Escherichia coli.
AB  - Mechanosensitive channels sense elevated membrane tension that arises from rapid
      water influx occurring when cells move from high to low osmolarity environments
      (hypoosmotic shock). These non-specific channels in the cytoplasmic membrane
      release osmotically-active solutes and ions. The two major mechanosensitive
      channels in Escherichia coli are MscL and MscS. Deletion of both proteins
      severely compromises survival of hypoosmotic shock. However, like many bacteria,
      E. coli cells possess other MscS-type genes (kefA, ybdG, ybiO, yjeP and ynaI).
      Two homologs, MscK (kefA) and YbdG, have been characterized as mechanosensitive
      channels that play minor roles in maintaining cell integrity. Additional channel
      openings are occasionally observed in patches derived from mutants lacking MscS,
      MscK and MscL. Due to their rare occurrence, little is known about these extra
      pressure-induced currents or their genetic origins. Here we complete the
      identification of the remaining E. coli mechanosensitive channels YnaI, YbiO and
      YjeP. The latter is the major component of the previously described MscM activity
      (~300 pS), while YnaI (~100 pS) and YbiO (~1000 pS) were previously unknown.
      Expression of native YbiO is NaCl-specific and RpoS-dependent. A Delta7 strain
      was created with all seven E. coli mechanosensitive channel genes deleted. High
      level expression of YnaI, YbiO or YjeP proteins from a multicopy plasmid in the
      Delta7 strain (MJFGH) leads to substantial protection against hypoosmotic shock.
      Purified homologs exhibit high molecular masses that are consistent with
      heptameric assemblies. This work reveals novel mechanosensitive channels and
      discusses the regulation of their expression in the context of possible
      additional functions.

PMID- 22874654
TI  - History of anaesthesia:  why did professional anaesthetists appear in Britain
      first?

PMID- 22874655
TI  - Why have a history section in a modern anaesthesia journal?

PMID- 22874656
TI  - ATP derived from astrocytes modulates memory in the chick.
AB  - Memory consolidation in a discriminative bead pecking task is modulated by
      endogenous adenosine triphosphate (ATP) acting at purinergic receptors in the
      hippocampus. Consolidation, from short- to intermediate- to long-term memory
      during two distinct periods following training, was blocked by the non-selective
      P2 purinergic receptor antagonist PPADS (pyridoxal phosphate-6-azo(benzene-2,4
      disulphonic acid) tetrasodium salt hydrate and the specific P2Y1 receptor
      antagonist MRS2179. Direct injections of the ATP agonists (ATPgammaS and
      ADPbetaS) potentiated memory consolidation and the effect of ADPbetaS was blocked
      by MRS2179, suggesting an important role of ATP on memory consolidation via the
      P2Y1 receptor in the chick hippocampus. Incubation of astrocytes with ATPgammaS
      and ADPbetaS resulted in the increase of intracellular calcium ([Ca2+]i), the
      latter being blocked by MRS2179 suggesting a specific role for P2Y1 receptors in
      the calcium response. This response was prevented by blocking astrocytic
      oxidative metabolism with fluoroacetate. We argue that the source of the ATP
      acting on neuronal P2Y1 receptors is most likely to be astrocytes. Thrombin
      selectively increases [Ca2+]i in astrocytes but not in neurones. The main
      findings of the present study are: (a) astrocytic [Ca2+]i plays an important role
      in the consolidation of short-term to long-term memory; and (b) ATP released from
      chick astrocytes during learning modulates neuronal activity through astrocytic
      P2Y1 receptors.

PMID- 22874657
TI  - Global standardisation of haemoglobin A(1c) using metrological principles.

PMID- 22874658
TI  - Improved statistical power of Alzheimer clinical trials by item-response theory:
      proof of concept by application to the activities of daily living scale.
AB  - Discovery of effective treatment for Alzheimer disease (AD) depends upon the
      availability of outcome measures that exhibit good sensitivity to rates of
      longitudinal decline on global functional performance. The Alzheimer's Disease
      Cooperative Study-Activities of Daily Living inventory (ADCS-ADL) is a frequently
      used functional endpoint in clinical trials for AD that assesses patient
      functional ability on the basis of informant ratings of patient performance on a
      variety of everyday tasks. Previous research has shown that the items comprising
      the ADCS-ADL are sensitive to characteristic longitudinal trajectories in AD.
      However, standard procedures for combining information from individual items into
      an overall test score may not make full use of the information provided by
      informant responses. The current study explored an application of item-response
      theory (IRT) techniques to the calculation of test scores on the ADCS-ADL. Using
      data from 2 ADCS clinical trials on mild-to-moderate AD patients we found that
      IRT based scoring increased sensitivity to change in functional ability and
      improved prospective statistical power of the ADCS-ADL as an outcome measure in
      clinical trials.

PMID- 22874659
TI  - The APOE epsilon4 allele is associated with increased frontally mediated
      neurobehavioral symptoms in amnestic MCI.
AB  - The apolipoprotein E epsilon4 allele is a risk factor for late-onset Alzheimer
      disease (AD), and the frontal lobes may be among the regions that manifest
      effects of epsilon4 even early in the disease. We predicted that among patients
      with amnestic mild cognitive impairment (aMCI) and AD, epsilon4 would be
      associated with increased neurobehavioral symptoms when assessed using a measure
      sensitive to frontal lobe integrity. We obtained cognitive data and caregiver
      ratings on the Frontal Systems Behavior Scale (FrSBe) for aMCI patients (N=29
      epsilon4 carriers; N=29 noncarriers) and AD patients (N=47 carriers; N=42
      noncarriers). In both diagnostic groups, epsilon4 carriers had lower scores on
      tests of memory but did not differ on cognitive screening measures or tests of
      executive functioning. There were no differences in retrospective caregiver
      ratings of preillness status on the FrSBe by epsilon4 status in either diagnostic
      group. However, in the aMCI group, epsilon4 carriers had elevated current FrSBe
      Executive Dysfunction scores in comparison with noncarriers. In the AD group,
      there were no differences in current FrSBe scores by genotype group. Results
      indicate that epsilon4-related behavior change occurs in the aMCI stage but may
      not be apparent by the AD stage.

PMID- 22874660
TI  - Do defective B cells contribute to reduced Treg cells and autoimmunity in
      patients with Common Variable Immunodeficiency?

PMID- 22874661
TI  - Comparing physical exercise in groups to group cognitive behaviour therapy for
      the treatment of panic disorder in a randomized controlled trial.
AB  - BACKGROUND: Previous studies have suggested that physical exercise can reduce
      symptoms for subjects suffering from panic disorder (PD). The efficacy of this
      intervention has so far not been compared to an established psychotherapy, such
      as cognitive behaviour therapy (CBT). Assessment of controlled long-term effects
      and the clinical significance of the treatment are also lacking. AIM: To compare
      physical exercise to CBT as treatment for PD, and assess controlled long-term and
      clinically significant effects. METHOD: PD-patients were randomized to either
      three weekly sessions of physical exercise (n = 17), or one weekly session of CBT
      (n = 19). Both treatments ran for 12 weeks, were manualized and administered in
      groups. Patients were assessed twice before the start of treatment, at post
      treatment and at 6 and 12 months thereafter. Primary outcome-measures consisted
      of the Mobility Inventory (MI), the Agoraphobia Cognitions Questionnaire (ACQ)
      and the Body Sensations Questionnaire (BSQ). RESULTS: A two-way repeated measures
      MANOVA of these measures demonstrated a significant effect of time, F(16, 544) =
      7.28, p < .01, as well as a significant interaction effect, F(16, 544) = 1.71, p
      < .05, in favour of CBT. This finding was supported by the assessment of
      clinically significant changes of avoidant behaviour and of treatment-seeking one
      year later. CONCLUSION: Group CBT is more effective than group physical exercise
      as treatment of panic disorder, both immediately following treatment and at
      follow-up assessments.

PMID- 22874662
TI  - Epidemiological investigation of Renibacterium salmoninarum in three Oncorhynchus
      spp. in Michigan from 2001 to 2010.
AB  - Bacterial kidney disease (BKD) has caused mortalities and chronic infections in
      wild and farm-raised salmonids throughout the world. In the Laurentian Great
      Lakes of North America, BKD was associated with several large-scale mortality
      events of Oncorhynchus spp. throughout the 1980s and 1990s. In response to these
      mortality events, the state of Michigan implemented several enhanced biosecurity
      measures to limit the occurrence of BKD in state-operated hatcheries and gamete
      collection weirs. The objectives of this study were to assess if infection levels
      (prevalence and intensity) of Renibacterium salmoninarum, the causative agent of
      BKD, have changed in broodstock and pre-stocking fingerlings of three feral
      Oncorhynchus spp. (Chinook salmon (O. tshawytscha), coho salmon (O. kisutch), and
      steelhead (O. mykiss)) over a decade, following the implementation of the
      enhanced biosecurity measures. Between 2001 and 2010, a total of 3,530 broodstock
      salmonids collected from lakes Huron and Michigan tributaries during spawning
      runs and 4,294 propagated pre-stocking salmonid fingerlings collected from three
      state of Michigan fish hatcheries were tested for the presence of R. salmoninarum
      antigens using the enzyme-linked immunosorbent assay. Substantial declines in the
      overall prevalence of the bacterium were detected in each of the examined
      broodstocks. Most propagated pre-stocking fingerlings also exhibited substantial
      declines in R. salmoninarum prevalence. Prevalence was typically higher in
      Chinook salmon from Lake Michigan than from Lake Huron; prevalence was also
      generally higher in the Hinchenbrooke strain of coho salmon than in the Michigan
      adapted strain. For most strains and stocks examined, intensity of R.
      salmoninarum infection was found to have declined. Although there were declines
      in the potential for shedding the bacteria for both male and female Chinook and
      coho salmon, overall shedding rates were generally low (<15%) except for
      Hinchenbrooke coho salmon strain, which had shedding prevalences in excess of 50%
      at the beginning of the study. This study provides evidence that enhanced
      biosecurity measures at culture facilities and collection sites are capable of
      severely curtailing disease infection in wild populations even at the scale of
      Lake Michigan fisheries.

PMID- 22874663
TI  - Breast-feeding duration: influence on taste acceptance over the first year of
      life.
AB  - Early feeding experiences, e.g. related to milk feeding, can affect later food
      and taste preferences. However, consequences of breast-feeding on taste
      acceptance are under-investigated. The objective of the present study was to
      examine the impact of exclusive breast-feeding duration (DEB) on taste acceptance
      at 6 and 12 months in the same infants (n 122). Mothers recorded the DEB.
      Acceptance of solutions of each of the five basic tastes relative to water was
      evaluated in the laboratory at 6 and 12 months by the ingestion ratio (IR).
      Kendall correlations were calculated between the DEB and the IR. Only 16 %
      completed at least 6 months of exclusive breast-feeding; 79 % had begun
      complementary feeding by 6 months. At 6 months, infants preferred sweet, salty
      and umami solutions over water and were indifferent to sour and bitter solutions.
      The longer an infant was breast-fed, the more s/he accepted the umami solution at
      6 months. At 12 months, infants preferred sweet and salty solutions over water
      and were indifferent to sour, bitter and umami solutions. The relationship
      between the DEB and acceptance of the umami solution was not observed at 12
      months. No relationship was observed between the DEB and sweet, salty, sour and
      bitter taste acceptance at 6 or 12 months. The association between the DEB and
      umami taste acceptance at 6 months may relate to the higher glutamate content of
      human milk compared with formula milk. Beyond the acknowledged metabolic benefits
      of breast-feeding, this suggests that prolonged breast-feeding could also be
      associated with an impact on sensory preference at the beginning of complementary
      feeding.

PMID- 22874664
TI  - Balance control in multiple sclerosis: correlations of trunk sway during stance
      and gait tests with disease severity.
AB  - OBJECTIVE: To investigate which measures of trunk sway taken during stance and
      gait tasks are best correlated with Expanded Disability Status Scale (EDSS)
      scores of multiple sclerosis (MS) patients. METHODS: We studied 37 MS patients
      (mean age 43+/-10 years; 76% female; 81% relapsing-remitting MS; mean EDSS score
      2.8+/-1.1). The study protocol comprised the subjective Dizziness Handicap
      Inventory (DHI) and recorded peak-to-peak trunk sway angles and velocities during
      14 stance and gait balance tasks. 76 age- and gender-matched healthy subjects
      served as controls (HCs). RESULTS: Patients had significant more trunk sway than
      HCs (p<0.001) and EDSS scores were highly correlated with sway measures in 6 of
      14 balance tests (rho>0.4; p<0.001). Patients with normal clinical Romberg and
      tandem gait tests showed significantly more trunk sway than HCs when standing on
      one leg eyes open on foam support (p<0.001). Patients with spinal cord
      manifestation of MS (n=27) had higher trunk sway compared to patients without.
      Mean DHI score of the patients was 30+/-23.5%. DHI was highly correlated with
      trunk sway for all two-legged stance tasks in MS patients. CONCLUSIONS: Balance
      deficits in trunk sway observed in MS patients during stance and gait tasks are
      highly correlated with their EDSS and DHI scores, with stance and tandem gait
      tasks providing the highest correlations. Measures of trunk sway during stance
      balance tests demonstrate a MS-related functional deficit even in patients with
      normal clinical Romberg and tandem gait tests, and therefore have the potential
      to provide objective data of sub-clinical deficits.

PMID- 22874665
TI  - Housing data-based socioeconomic index and risk of invasive pneumococcal disease:
      an exploratory study.
AB  - We previously developed and validated an index of socioeconomic status (SES)
      termed HOUSES (housing-based index of socioeconomic status) based on real
      property data. In this study, we assessed whether HOUSES overcomes the absence of
      SES measures in medical records and is associated with risk of invasive
      pneumococcal disease (IPD) in children. We conducted a population-based case
      control study of children in Olmsted County, MN, diagnosed with IPD (1995-2005).
      Each case was age- and gender-matched to two controls. HOUSES was derived using a
      previously reported algorithm from publicly available housing attributes (the
      higher HOUSES, the higher the SES). HOUSES was available for 92.3% (n = 97) and
      maternal education level for 43% (n = 45). HOUSES was inversely associated with
      risk of IPD in unmatched analysis [odds ratio (OR) 0.22, 95% confidence interval
      (CI) 0.05-0.89, P = 0.034], whereas maternal education was not (OR 0.77, 95% CI
      0.50-1.19, P = 0.24). HOUSES may be useful for overcoming a paucity of
      conventional SES measures in commonly used datasets in epidemiological research.

PMID- 22874666
TI  - The effect of lifetime cumulative adversity on change and chronicity in
      depressive symptoms and quality of life in older adults.
AB  - BACKGROUND: Lifetime cumulative adversity (LCA) has a detrimental effect on
      mental health. However, it is less clear whether it also increases the risk for
      mental health deterioration across time, and whether it is related to a
      continuous impairment in mental health among older adults. The current study
      aimed to examine whether LCA is related to deterioration and to continuous
      vulnerability in depressive symptoms and quality of life. METHOD: Nine thousand
      one hundred fifty four older adults (mean age = 63 at Wave 1) who participated in
      the first three waves of the Survey of Health, Ageing and Retirement in Europe
      (SHARE) reported exposure to negative life events, depressive symptoms, and
      quality of life. RESULTS: Respondents with more LCA were at greater risk of high
      level of depressive symptoms and low level of quality of life. Those with more
      adversity were at greater risk of reporting an increase in depressive symptoms
      and a decrease in quality of life between waves. LCA was also related to
      continuous high level of depressive symptoms and low level of quality of life.
      The effect of LCA was stronger for depressive symptoms than for quality of life.
      CONCLUSIONS: LCA is associated with decline, as well as with continuous
      impairment, in major markers of mental health at the second half of life. The
      overall modest effects imply that resilience to LCA is widespread among older
      adults. Still, prevention and intervention programs should target old people with
      cumulative adversity, as they are in risk for deterioration and chronic
      vulnerability in important components of mental health.

PMID- 22874667
TI  - S-nitrosylation of Cdk5: potential implications in amyloid-beta-related
      neurotoxicity in Alzheimer disease.
AB  - Aberrant activation of Cdk5 has been implicated in the process of
      neurodegenerative diseases such as Alzheimer's disease (AD). We recently reported
      that S-nitrosylation of Cdk5 (forming SNO-Cdk5) at specific cysteine residues
      results in excessive activation of Cdk5, contributing to mitochondrial
      dysfunction, synaptic damage, and neuronal cell death in models of AD.
      Furthermore, SNO-Cdk5 acts as a nascent S-nitrosylase, transnitrosylating the
      mitochondrial fission protein Drp1 and enhancing excessive mitochondrial fission
      in dendritic spines. However, a molecular mechanism that leads to the formation
      of SNO-Cdk5 in neuronal cells remained obscure. Here, we demonstrate that
      neuronal nitric oxide synthase (NOS1) interacts with Cdk5 and that the close
      proximity of the two proteins facilitates the formation of SNO-Cdk5.
      Interestingly, as a negative feedback mechanism, Cdk5 phosphorylates and
      suppresses NOS1 activity. Thus, together with our previous report, these findings
      delineate an S-nitrosylation pathway wherein Cdk5/NOS1 interaction enhances SNO
      Cdk5 formation, mediating mitochondrial dysfunction and synaptic loss during the
      etiology of AD.

PMID- 22874668
TI  - Generation of a novel murine model of Abeta deposition based on the expression of
      human wild-type amyloid precursor protein gene.
AB  - Mouse models of Alzheimer disease (AD) have been generated based on Amyloid-beta
      Precursor Protein (AbetaPP) and the Presenilin (PSEN) gene mutations associated
      with familial AD (FAD). Such models have provided valuable insights into AD
      pathogenesis and represent an important research tool for the discovery of
      potential treatments. To model amyloid deposition in AD, we generated a new mouse
      line based on the presence of two copies of the genomic region encoding human
      wild-type AbetaPP as well as a mutation (L166P) in the murine Psen1. By ~6 months
      of age, these mice have begun to develop cerebral Abeta pathology with a
      significant increase in the levels of AbetaPP C-terminal fragments and Abeta42,
      as well as increase Abeta42/Abeta40 ratio. Since in the brain and other tissues
      of these mice, wild-type human AbetaPP mRNA and protein levels are comparable to
      those of endogenous AbetaPP, this model may allow studies about the role of
      AbetaPP isoforms in the pathogenesis of AD. This animal model may be suitable to
      test drugs aimed at inhibiting expression or altering splicing and processing of
      AbetaPP, without artifacts associated with the presence of mutations in AbetaPP
      or overexpression due to the use of exogenous promoters. These features of the
      new model are of critical importance in assessing the success of therapeutic
      interventions.

PMID- 22874669
TI  - Alzheimer Abeta peptide interactions with lipid membranes: fibrils, oligomers and
      polymorphic amyloid channels.
AB  - Fibrillar aggregates of misfolded amyloid proteins are involved in a variety of
      diseases such as Alzheimer disease (AD), type 2 diabetes, Parkinson, Huntington
      and prion-related diseases. In the case of AD amyloid beta (Abeta) peptides, the
      toxicity of amyloid oligomers and larger fibrillar aggregates is related to
      perturbing the biological function of the adjacent cellular membrane. We used
      atomistic molecular dynamics (MD) simulations of Abeta 9-40 fibrillar oligomers
      modeled as protofilament segments, including lipid bilayers and explicit water
      molecules, to probe the first steps in the mechanism of Abeta-membrane
      interactions. Our study identified the electrostatic interaction between charged
      peptide residues and the lipid headgroups as the principal driving force that can
      modulate the further penetration of the C-termini of amyloid fibrils or fibrillar
      oligomers into the hydrophobic region of lipid membranes. These findings advance
      our understanding of the detailed molecular mechanisms and the effects related to
      Abeta-membrane interactions, and suggest a polymorphic structural character of
      amyloid ion channels embedded in lipid bilayers. While inter-peptide hydrogen
      bonds leading to the formation of beta-strands may still play a stabilizing role
      in amyloid channel structures, these may also present a significant helical
      content in peptide regions (e.g., termini) that are subject to direct
      interactions with lipids rather than with neighboring Abeta peptides.

PMID- 22874670
TI  - Genetic variability of the gene cluster CALHM 1-3 in sporadic Creutzfeldt-Jakob
      disease.
AB  - Perturbations of calcium homeostasis have been associated with several
      neurodegenerative disorders. A common polymorphism (rs2986017) in the CALHM1
      gene, coding for a regulator of calcium homeostasis, is a genetic risk factor for
      the development of Alzheimer disease (AD). Although some authors failed to
      confirm these results, a meta-analysis has shown that this polymorphism modulates
      the age at disease onset. Furthermore, a recent association study has explored
      the genetic variability of CALHM1 gene and two adjacent paralog genes (CALHM3 and
      CALHM2) in an Asian population. Since several lines of evidence suggest that AD
      and prion diseases share pathophysiologic mechanisms, we investigated for the
      first time the genetic variability of the gene cluster formed by CALHM1 and its
      paralogs in a series of 235 sporadic Creutzfeldt-Jakob disease (sCJD) patients,
      and compared the genotypic and allelic frequencies with those presented in 329
      controls from the same ancestry. As such, this work also represents the first
      association analysis of CALHM genes in sCJD. Sequencing analysis of the complete
      coding regions of the genes demonstrated the presence of 10 single nucleotide
      polymorphisms (SNP) within the CALHM genes. We observed that rs4918016-rs2986017
      rs2986018 and rs41287502-rs41287500 polymorphic sites at CALHM1 were in linkage
      disequilibrium. We found marginal associations for sCJD risk at CALHM1
      polymorphic sites rs41287502 and rs41287500 [coding for two linked missense
      mutations (p.(Met323Ile); (Gly282Cys)], and rs2986017 [p.(Leu86Pro)].
      Interestingly, a TGG haplotype defined by the rs4918016-rs2986017-rs2986018 block
      was associated with sCJD. These findings underscore the need of future
      multinational collaborative initiatives in order to corroborate these seminal
      data.

PMID- 22874672
TI  - Dysfunction of microtubule-associated proteins of MAP2/tau family in Prion
      disease.
AB  - The aggregation of PrP (Sc)  is thought to be crucial for the neuropathology of
      prion diseases. A growing body of evidence demonstrates that the perturbation of
      the microtubule network contributes to PrP (Sc) -mediated neurodegeneration.
      Microtubules are a component of the cytoskeleton and play a central role in
      organelle transport, axonal elongation and cellular architecture in neurons. The
      polymerization, stabilization, arrangement of microtubules can be modulated by
      interactions with a series of microtubule-associated proteins (MAPs). Recent
      studies have proposed the abnormal alterations of two major microtubule
      associated proteins, tau and MAP2, in the brain tissues of naturally occurred and
      experimental human and animal prion diseases. Increased total tau protein and
      hyperphosphorylation of tau at multiple residues are observed at the terminal
      stage of prion disease. The abnormal aggregation of tau protein disturbs its
      binding ability to microtubules and affects the microtubule dynamic.
      Significantly downregulated MAP2 is detected in the brain tissues of scrapie
      infected hamsters and PrP106-126 treated cells, which corresponds well with the
      remarkably low levels of tubulin. In conclusion, dysfunction of MAP2/tau family
      leads to disruption of microtubule structure and impairment of axonal transport,
      and eventually triggers apoptosis in neurons, which becomes an essential pathway
      for prion to induce the neuropathology.

PMID- 22874671
TI  - DNA aptamers detecting generic amyloid epitopes.
AB  - Amyloids are fibrillar protein aggregates resulting from non-covalent
      autocatalytic polymerization of various structurally and functionally unrelated
      proteins. Previously we have selected DNA aptamers, which bind specifically to
      the in vitro assembled amyloid fibrils of the yeast prionogenic protein Sup35.
      Here we show that such DNA aptamers can be used to detect SDS-insoluble amyloid
      aggregates of the Sup35 protein, and of some other amyloidogenic proteins,
      including mouse PrP, formed in yeast cells. The obtained data suggest that these
      aggregates and the Sup35 amyloid fibrils assembled in vitro possess common
      conformational epitopes recognizable by aptamers. The described DNA aptamers may
      be used for detection of various amyloid aggregates in yeast and, presumably,
      other organisms.

PMID- 22874675
TI  - Radiofrequency energy delivery to the lower esophageal sphincter reduces
      esophageal acid exposure and improves GERD symptoms: a systematic review and meta
      analysis.
AB  - PURPOSE: Studies of endoscopic application of radiofrequency energy to the lower
      esophageal sphincter for gastroesophageal reflux control have produced
      conflicting reports of its effectiveness. This study aimed to conduct a meta
      analysis of randomized controlled trials and cohort studies to assess the impact
      of this treatment. METHODS: Twenty studies were included. Outcomes analyzed
      included gastroesophageal reflux disease (GERD) symptom assessment, quality of
      life, esophageal pH, and esophageal manometry. RESULTS: A total of 1441 patients
      from 18 studies were included. Radiofrequency treatment improved heartburn scores
      (P=0.001), and produced improvements in quality of life as measured by GERD
      health-related quality-of-life scale (P=0.001) and quality of life in reflux and
      dyspepsia score (P=0.001). Esophageal acid exposure decreased from a preprocedure
      Johnson-DeMeester score of 44.4 to 28.5 (P=0.007). CONCLUSIONS: Radiofrequency
      ablation of the lower esophageal sphincter produces significant improvement in
      reflux symptoms and may represent an alternative to medical treatment and
      surgical fundoplication in select patients.

PMID- 22874674
TI  - A modern approach to the treatment of most common foregut diseases.

PMID- 22874673
TI  - The P's and Q's of cellular PrP-Abeta interactions.
AB  - Prion disease research has opened up the "black-box" of neurodegeneration,
      defining a key role for protein misfolding wherein a predominantly alpha-helical
      precursor protein, PrP (C), is converted to a disease-associated, beta-sheet
      enriched isoform called PrP (Sc). In Alzheimer disease (AD) the Abeta peptide
      derived from the beta-amyloid precuror protein APP folds in beta-sheet amyloid.
      Early thoughts along the lines of overlap may have been on target, (1) but were
      eclipsed by a simultaneous (but now anachronistic) controversy over the role of
      PrP (Sc) in prion diseases. (2) (,) (3) Nonetheless, as prion diseases such as
      Creutzfeldt-Jakob Disease (CJD) are themselves rare and can include an overt
      infectious mode of transmission, and as familial prion diseases and familial AD
      involve different genes, an observer might reasonably have concluded that prion
      research could occasionally catalyze ideas in AD, but could never provide
      concrete overlaps at the mechanistic level. Surprisingly, albeit a decade or
      three down the road, several prion/AD commonalities can be found within the
      contemporary literature. One important prion/AD overlap concerns seeded spread of
      Abeta aggregates by intracerebral inoculation much like prions, (4) and, with a
      neuron-to-neuron 'spreading' also reported for pathologic forms of other
      misfolded proteins, Tau (5) (,) (6) and alpha-synuclein in the case of Parkinson
      Disease. (7) (,) (8) The concept of seeded spread has been discussed extensively
      elsewhere, sometimes under the rubric of "prionoids" (9), and lies outside the
      scope of this particular review where we will focus upon PrP (C). From this point
      the story can now be subdivided into four strands of investigation: (1)
      pathologic effects of Abeta can be mediated by binding to PrP (C), (10) (2) the
      positioning of endoproteolytic processing events of APP by pathologic (beta
      cleavage + gamma-cleavage) and non-pathologic (alpha-cleavage + gamma-cleavage)
      secretase pathways is paralleled by seemingly analogous alpha- and beta-like
      cleavage of PrP (C) (Fig. 1) (3) similar lipid raft environments for PrP (C) and
      APP processing machinery, (11) (-) (13) and perhaps in consequence, overlaps in
      repertoire of the PrP (C) and APP protein interactors ("interactomes"), (14) (,)
      (15) and (4) rare kindreds with mixed AD and prion pathologies. (16) Here we
      discuss confounds, consensus and conflict associated with parameters that apply
      to these experimental settings.

PMID- 22874676
TI  - Medium and long-term outcomes after pneumatic dilation or laparoscopic Heller
      myotomy for achalasia: a meta-analysis.
AB  - Recent randomized studies comparing outcomes after pneumatic dilation (PD) and
      laparoscopic Heller myotomy (LHM) for the treatment of achalasia are conflicting
      and limited to short-term follow-up. Our meta-analysis compared the long-term
      durability of these approaches, with the hypothesis that LHM offers superior long
      term remission compared with PD. We identified 36 studies published between 2001
      and 2011 with at least 5 years of follow-up. Those studies describing PD included
      3211 patients (mean age, 49.8 y). For PD, the mean 5-year remission rate was
      61.9% and the mean 10-year remission rate was 47.9%. Overall, 1526 patients (mean
      age, 46.3 y) were treated with LHM; 83% received a fundoplication. In contrast,
      the mean 5- and 10-year remission rates after LHM were 76.1% and 79.6%,
      respectively. Finally, the perforation rate for LHM was twice that of PD (4.8%
      vs. 2.4%; P<0.05). We conclude that despite a higher frequency of perforation,
      LHM affords greater long-term durability.

PMID- 22874677
TI  - Modern treatment of paraesophageal hernia:  preoperative evaluation and technique
      for laparoscopic repair.
AB  - This article reviews the preoperative evaluation of patients with paraesophageal
      hernia (PEH) and details the principles and components of a laparoscopic PEH
      repair. Complete hernia sac dissection and excision, adequate esophageal
      mobilization, reapproximation of the crura, and creation of an antireflux barrier
      make up the key steps in any repair and are described. Although the preferred
      operative approach to PEH has undergone significant modification, especially
      since the introduction of minimally invasive laparoscopic techniques, many
      controversies still exist. The decision of whether to use mesh to reinforce the
      crural closure remains an unresolved issue in the surgical literature, and
      further evolution in this and other areas of PEH surgery is sure to occur in the
      near future.

PMID- 22874678
TI  - Robotic applications in the treatment of diseases of the esophagus.
AB  - Minimally invasive treatment of esophageal diseases such as gastroesophageal
      reflux disease, achalasia, and esophageal cancer is associated with many of the
      benefits observed after the minimally invasive surgery for other diseases (such
      as symptomatic cholelithiasis) when compared with the open approach. Laparoscopic
      treatment of these esophageal conditions is technically complex and subject to
      several inherent limitations. Robotic surgical systems may allow surgeons to
      overcome many of these obstacles, enabling more widespread adaptation of these
      techniques.

PMID- 22874679
TI  - A critical review of minimally invasive esophagectomy.
AB  - The advent of minimally invasive esophagectomy (MIE) attempts to decrease
      postoperative complications and mortality for this high-risk procedure. This
      review examines techniques in MIE, associated outcomes, and offers a critical
      appraisal of the literature surrounding this procedure. A Pubmed search was
      conducted for "minimally invasive esophagectomy" and associated synonyms. In
      addition, we analyze the outcomes at our institution through a prospectively
      maintained database. With varied techniques and utilization of different
      endpoints it is difficult to draw concrete conclusions from the current
      literature. Overall, however, there is no strong trend toward deceased mortality
      or decreased pulmonary complications from MIE, but there is a trend toward
      decreased intraoperative blood loss and shorter intensive care unit and ward
      stays. Until future studies are completed, MIE remains a useful tool in the
      armamentarium of the esophageal surgeon, and should be used not in exclusion of
      other approaches should patient or tumor factors dictate otherwise.

PMID- 22874680
TI  - Single-incision appendectomy is comparable to conventional laparoscopic
      appendectomy: a systematic review and pooled analysis.
AB  - PURPOSE: Acute appendicitis remains the common gastrointestinal emergency in
      adults. Single-incision laparoscopic appendectomy (SILA) has been proposed as the
      next evolution in minimally invasive surgery. SILA is postulated to reduce
      postoperative pain and enhance cosmesis, while effectively removing an inflamed
      appendix. However, the efficacy and benefits of SILA compared with conventional
      laparoscopic appendectomy (CLA) remain to be determined. Our objectives were to
      systematically review the literature comparing SILA with CLA for acute
      appendicitis and perform a pooled analysis on the efficacy of SILA. METHODS:
      Published English-language manuscripts were considered for review inclusion. A
      comprehensive search of electronic databases (eg, MEDLINE, EMBASE, SCOPUS, BIOSIS
      Previews, and the Cochrane Library) using broad search terms was completed. All
      comparative studies were included if they incorporated adult patients undergoing
      appendectomy for acute appendicitis by SILA. The primary outcomes of interest
      were operative time and length of hospital stay. RESULTS: From a total of 366
      articles, 34 articles were identified. A total of 9 comparative studies were
      included for pooled analysis. There was no significant difference in operative
      time, length of stay, pain scores, and conversion or complication rates between
      SILA and CLA for acute appendicitis. CONCLUSIONS: This systematic review and
      pooled analysis demonstrates that SILA is comparable to CLA for acute
      appendicitis in adults. However, this review identifies the need for randomized
      controlled trials to clarify the efficacy of SILA compared with CLA.

PMID- 22874681
TI  - Assessment of the clinical usefulness of imaging modalities in identifying
      postoperative upper gastrointestinal tract leaks requiring reoperation.
AB  - PURPOSE: To assess the usefulness of imaging modalities in the diagnosis and
      determination of whether postoperative upper gastrointestinal tract leak (UGITL)
      requires operative intervention. METHODS: : Patients with suspected UGITL who
      underwent reoperation <= 30 days after the primary operation with intraoperative
      confirmation of leaks were identified. Data of those patients who had undergone
      computerized tomography (CT) or upper gastrointestinal contrast study (UGIS)
      before reoperation were reviewed. The usefulness and impact of imaging studies
      obtained before reoperation were evaluated. RESULTS: Thirty patients with
      confirmed UGITL were identified, 24 of whom had undergone imaging studies before
      reoperation. Fourteen CTs (63.7%) and 4 UGIS (67%) were positive or highly
      indicative of UGITL. The interval between the primary operation and the
      reoperation and the morbidity rates after the reoperation were similar between
      patients with and those without imaging studies before the reoperation (5.6 +/-
      4.8 vs. 6.8 +/- 4.2 d, P=0.55; 91.6% vs. 100%, P=0.29, respectively). False
      negative imaging results caused postponement of reoperation by >= 24 hours in 4
      patients whose outcome was similar to those with true-positive results.
      CONCLUSIONS: CTs and UGIS are supportive tools when deciding whether to reoperate
      for postoperative UGITL. However, a negative imaging study for UGITL does not
      exclude it definitively, and therefore should not replace clinical evaluations.

PMID- 22874682
TI  - Rectus abdominus fascial sheath usage for crural reinforcement during surgical
      management of GERD: preliminary report of a prospective randomized clinical
      trial.
AB  - PURPOSE: Many materials are currently being used to reinforce the crural repair.
      Perforation, intensive fibrosis, and price are limiting the usage of these
      materials. Our purpose was to seek an alternative, cheap, always available, and
      inert material to use for cruroplasty reinforcement. METHODS: Twenty-four
      patients participated and were randomly divided into 2 groups (graft+laparoscopic
      Nissen fundoplication and laparoscopic Nissen fundoplication alone) with 12
      patients in each group. Total operation time, postoperative dysphagia rate,
      dysphagia improvement time, postoperative pain, recurrence, and incisional hernia
      rate were compared. RESULTS: There was no difference in terms of study parameters
      between both groups except for the mean operation time. CONCLUSIONS: Autograft
      hiatoplasty seems to be a good alternative for crural reinforcement. It provides
      safe reinforcement, has the same dysphagia rates as meshless hiatoplasty, and
      avoids potential complications of redo surgery by minimizing extensive fibrosis.
      Furthermore, the rectus abdominus sheath is always available and inexpensive.

PMID- 22874683
TI  - the outcome of single-incision laparoscopic right colectomy for colon carcinoma
      in the elderly.
AB  - PURPOSE: Surgeons are increasingly being faced with the problem of treating
      elderly colon cancer patients. The purpose of this study was to elucidate the
      feasibility of single-incision laparoscopic surgery for these patients. METHODS:
      Among 34 right colon cancer patients treated with single-incision laparoscopic
      surgery procedure between August 2010 and September 2011, 9 (26.5%) were aged 80
      or over. The results of treatment in this elderly group were compared
      retrospectively with those in 10 younger colon cancer patients (age, 59 to 67 y;
      control group, 29.5%). RESULTS: The sex distribution, body mass index, and the
      tumor location were similar between the groups. The elderly had a higher
      incidence of preoperative risk factors (77.7% vs. 40.0%; P=0.17). However,
      operative time and estimated blood loss were similar and postoperative
      complications had not occurred in both groups. CONCLUSIONS: We believe that
      single-incision laparoscopic colectomy can be carried out safely in elderly
      patients with colon cancer.

PMID- 22874684
TI  - Indocyanine green reinjection technique for use in fluorescent angiography
      concomitant with cholangiography during laparoscopic cholecystectomy.
AB  - BACKGROUND: For safe laparoscopic cholecystectomy, surgeons must possess detailed
      knowledge of the anatomy of the bile duct and arterial system as seen through a
      laparoscope. STUDY DESIGN: We developed an indocyanine green (ICG) reinjection
      technique for use in fluorescent angiography. Here, we evaluated the efficacy of
      the ICG reinjection technique in fluorescent angiography in discriminating the
      arterial system with the concomitant use of fluorescent cholangiography. RESULTS:
      Twenty-eight patients were enrolled in the study. All patients underwent
      laparoscopic cholecystectomy without complication. After reinjection of ICG
      during surgery, fluorescence of the cystic artery was visualized in 25 patients
      (89%). CONCLUSIONS: Fluorescent angiography using this ICG reinjection technique
      might enhance the safety of laparoscopic cholecystectomy.

PMID- 22874685
TI  - A randomized trial comparing the use of endobiliary stent and T-tube for biliary
      decompression after laparoscopic common bile duct exploration.
AB  - PURPOSE: To compare the use of a biliary stent with T-tube for biliary
      decompression after laparoscopic common bile duct (CBD) exploration. METHODS:
      Between September 2004 and March 2008, 60 patients undergoing laparoscopic CBD
      exploration for CBD stones were randomized to choledochotomy closure over either
      a biliary stent or a T-tube after CBD clearance. Patients at high risk for
      surgery and unremitting cholangitis requiring preoperative endoscopic biliary
      drainage were excluded. RESULTS: There were 29 and 31 patients in the T-tube and
      stenting groups, respectively. The 2 groups were comparable with respect to their
      demographic profile and disease characteristics. Patients in the stent group had
      a significantly shorter operative time and postoperative stay with an earlier
      return to normal activity (P<0.0001). CONCLUSIONS: Choledochotomy closure over a
      stent results in a shorter postoperative stay and an earlier return to normal
      activity compared with closure over a T-tube without any increase in morbidity.

PMID- 22874686
TI  - Transanal single-port access microsurgery (TSPAM).
AB  - Transanal single-port access microsurgery (TSPAM) is an emerging and feasible
      minimally invasive method for the transanal excision of large sessile adenomas
      and early-stage carcinomas of the rectum. Here we present our TSPAM experience on
      rectal adenomas (high-grade rectal adenomas in 5 cases and carcinoma in situ in 1
      case). TSPAM is an innovative method that can be an affordable and disseminated
      alternative to transanal endoscopic microsurgery for the local excision of the
      rectal lesions.

PMID- 22874687
TI  - Single-incision laparoscopic versus conventional laparoscopic ventral hernia
      repair: a comparison of short-term surgical results.
AB  - AIM: To demonstrate the feasibility of single-port incisional hernia repair,
      quantify incision size, and compare results of patients operated by standard
      laparoscopy (SL) with those operated by the single-port technique
      [laparoendoscopic single-site surgery (LESS)]. METHODS: Prospective data
      collected on patients operated from March 2008 to June 2010. Indication for
      surgery was incisional hernia >3 cm. There were no selection criteria for the
      enrollment of patients or the operative technique used. RESULTS: Thirty-four
      patients were operated (18 women and 16 men): 15 with LESS and 19 with SL. There
      was no difference for age, body mass index, ASA scores, or number of previous
      surgical procedures. LESS patients had slightly larger (82 +/- 54 vs. 64 +/- 34
      mm) and more numerous hernias: 3 (1 to 7) versus 1 (1 to 3). Adhesion grades,
      severity scores, and operating times (78.2 SD +/- 31.2 vs. 73.5 SD +/- 25.4 min,
      P=0.76) did not differ between the groups. The mean fascia incision size in LESS
      was digitally measured as 12.93 +/- 2.01 mm. The hospital stay was a median of 1
      day in both groups. There was 1 conversion in the SL group. The median follow-up
      time was 26 months (range, 25 to 31 mo) for LESS and 34 months (range, 31 to 42
      mo) for SL. COMPLICATIONS: There were 2 seromas and 1 hematoma in the LESS group.
      In the SL group, there were 2 small-bowel injuries and 2 seromas. There were no
      recurrences in the SL group, 1 in LESS, and no port-site hernia so far.
      CONCLUSIONS: LESS incisional hernia repair through 1 minimal fascia incision is
      feasible. Early results do not indicate a longer operation time, higher
      complication, or higher recurrence rates.

PMID- 22874688
TI  - The role of diagnostic laparoscopy in detecting minimal peritoneal metastatic
      deposits in patients with pancreatic cancer scheduled for curative resection.
AB  - BACKGROUND: Pancreatic cancer (PC) is an aggressive disease usually diagnosed at
      an advanced stage. Modern computed tomography can define the subgroup of operable
      patients. However, minimal peritoneal deposits can be undetected even by modern
      computed tomography protocols. AIM: To diagnose those patients who are not
      operable because of a peritoneal spread using diagnostic laparoscopy (DL), thus
      avoiding unnecessary laparotomies. METHODS: A retrospective study was conducted
      on 52 consecutive patients with PC scheduled for curative pancreatic surgery.
      RESULTS: Out of 52 patients who underwent DL, peritoneal spread was diagnosed in
      5 patients and these patients were denied surgery. Laparoscopy did not detect 2
      other patients with peritoneal spread. CONCLUSIONS: Although the added value of
      DL in patients with PC is small (around 10% in our series), considering the
      minimal morbidity and costs attributed to this procedure, we believe that it
      should be adopted as a routine approach.

PMID- 22874689
TI  - Single-port laparoscopic cholecystectomy in patients of advanced age: why not?
AB  - OBJECTIVE: To compare the perioperative outcome of elderly patients undergoing
      either single-port cholecystectomy (SPC) or standard multiport laparoscopic
      cholecystectomy (SMLC). PATIENTS AND METHODS: Patients older than 50 years who
      underwent SPC using the reusable X-Cone were compared with age-matched, sex
      matched, and body mass index-matched patients after SMLC, and postoperative
      outcome was analyzed. RESULTS: Of 97 patients who underwent SPC during July 2009
      and August 2011, 33 patients (34%) were older than 50 years. Baseline
      characteristics were comparable for either group, as was the operative time (min)
      (SPC: 82.7 +/- 25.1 vs. SMLC: 83.9 +/- 22.1; P=0.85), postoperative hospital stay
      (d) (SPC: 3.7 +/- 1.6 vs. SMLC: 3.9 +/- 1.5; P=0.61), and postoperative
      complication rate [SPC: 4 of 33 patients (12.1%) vs. SMLC: 3 of 33 patients
      (9.1%); P=1.0]. CONCLUSIONS: Our study suggests that older age might not be
      predictive of an inferior outcome after SPC, compared with patients who were
      treated with the "golden standard."

PMID- 22874690
TI  - Outcomes of open versus laparoscopic procedure for synchronous radical resection
      of liver metastatic colorectal cancer:  a comparative study.
AB  - BACKGROUND: The laparoscopic resection of colorectal cancer (CRC) along with
      synchronous liver metastases has been attempted and reported in multiple single
      series. In this study, we aimed to examine the feasibility, procedural safety,
      and oncological integrity of 1-stage totally laparoscopic procedure for the
      radical resection of liver metastatic CRC in a head-to-head comparison with the 1
      stage open procedure simultaneously. METHODS: The patients who underwent
      selective 1-stage concomitant resection of CRC and synchronous liver metastases
      between January 2004 and December 2008 (laparoscopy group, n=13) were
      retrospectively enrolled in the study. Patients receiving open 1-stage resection
      (laparotomy group) were retrospectively included at the ratio of 1:1 (n=13 out of
      71), matching the laparoscopy group in sex, age, body mass index, site and stage
      of primary tumor, location and size of liver metastases, and adjuvant therapies.
      RESULTS: All the thirteen 1-stage laparoscopic procedures were successfully
      completed, without conversion to open procedure or additional incision. The
      operative duration of laparoscopic procedure was shorter than that of open
      procedure (313 +/- 44 vs. 350 +/- 46 min, P<0.05). The volume of blood loss was
      comparable between the 2 groups (259 +/- 111 vs. 273 +/- 95 mL, P>0.05). Patients
      undergoing laparoscopic procedure resumed off-bed activities, bowel movement, and
      oral intake earlier than those undergoing open procedure, and also had a shorter
      hospitalization stay (8.5 +/- 1.9 vs. 11.2 +/- 1.8 d, P<0.05). Only 1 clinically
      significant adverse event occurred in a patient who developed bile leak after the
      laparoscopic resection. The 1-, 3-, and 5-year survival rates were comparable
      between the 2 groups (P>0.05). CONCLUSIONS: One-stage synchronous laparoscopic
      resection of liver metastatic CRC is a feasible, effective, and safe modality in
      specifically indicated patients, both accelerating postoperative recovery and
      shortening hospitalization time.

PMID- 22874691
TI  - Lobe-specific unidirectional stapling strategy in video-assisted thoracic surgery
      lobectomy.
AB  - PURPOSE: To evaluate the feasibility of the lobe-specific unidirectional stapling
      strategy (LSUS) strategy in video-assisted thoracic surgery (VATS) lobectomy.
      METHODS: A retrospective analysis was conducted on 123 patients, who underwent
      VATS lobectomy using LSUS. The vein, artery, and bronchus of each lobe were
      stapled through a lobe-specific port. The posteroinferior port, in the eighth
      intercostal space on the posterior axillary line, was the stapler port in upper
      or middle lobectomies. The anteroinferior port, in the sixth intercostal space on
      the anterior axillary line, was used for each lower lobectomy. RESULTS: VATS
      lobectomy was completed in 116 (94%) patients and LSUS was successful for every
      lobectomy in these patients. There were no adverse events related to stapling.
      Fifteen patients experienced postoperative complications. The operative mortality
      rate was 1.7%. The mean pain score on the first postoperative day was 3.2 out of
      10. CONCLUSIONS: LSUS is feasible and safe for all type of VATS lobectomy.

PMID- 22874692
TI  - The comparative effects of transdermal and intramuscular diclofenac on
      postlaparoscopic surgery pain.
AB  - PURPOSE: Postlaparoscopic surgery pain management can reduce the discharge and
      recovery time. Thus conventional nonsteroidal anti-inflammatory drugs and opioids
      have been used for this purpose. The aim of this trial was to compare the
      analgesic and opioid-sparing efficacy of diclofenac sodium intramuscular (IM)
      with diclofenac transdermal patch in the management of postlaparoscopy pain.
      METHODS: Patients were randomized to receive IM diclofenac 75 mg (n=30) 15
      minutes before anesthesia or transdermal diclofenac (n=30) 3 hours before
      laparoscopic surgery. Transdermal or IM diclofenac were reapplied 12 hours later.
      All patients were administered tramadol intravenously before surgery.
      Postoperative pain management was maintained with tramadol using a patient
      controlled analgesia device. Postoperative visual analogue pain scores (VAS, 0 to
      10 cm) and adverse reactions were recorded over a 24-hour period. If VAS values
      were >4, 25 mg tramadol was given intravenously as a rescue analgesic. RESULTS:
      In both groups, VAS scores were higher in the first 4 hours. There were no
      significant differences in postoperative pain between the 2 groups. The
      postoperative tramadol consumption, and rescue analgesic needs of the patients
      between both groups were not statistically significant. Injection pain was
      observed in the IM diclofenac group, but for both groups no skin reactions were
      observed at the application sites of the drugs. CONCLUSIONS: Diclofenac
      transdermal patch provided pain relief for postoperative laparoscopic surgery as
      effectively as IM diclofenac and can be used.

PMID- 22874693
TI  - Mechanical analysis of the formation of forceps and scope for single-port
      laparoscopic surgery.
AB  - BACKGROUND: The aim of this study is to demonstrate a shaft formation of forceps
      and scope which provides higher degree of freedom of motion for single-port
      laparoscopic surgery (SPLS). The key to smoothly performing SPLS lies in
      understanding the formation in which the shaft conflict is minimized. However,
      there have been no reported studies on conflict reduction in SPLS from a shaft
      formation perspective. METHODS: When performing SPLS, 3 instruments are passed
      into a narrow space, only 2 patterns of shaft formation can be obtained: a
      formation in which the 3 instruments rotate clockwise or counterclockwise
      (rotation formation) or a formation in which 1 instrument passes between the
      other 2 (cross formation). So motion spaces of the instruments in rotation
      formation compared with that in cross formation were tested using engineering
      methods. The range of the forceps' motion was assumed to be the space covered by
      the forceps till collision occurred between the moving forceps and either the
      other fixed forceps or the fixed scope. Examination of the range of movement of
      the scope was conducted in the same manner. The motion space with the area on the
      x-y horizontal is evaluated, as viewed from the peritoneal umbilicus port entry
      area. RESULTS: The motion area of each instrument in rotation formation is 1.9 to
      2.6 times wider than that in cross formation. CONCLUSIONS: Rotation formation
      provides high degree of freedom of motion for SPLS.

PMID- 22874694
TI  - A minimally invasive approach to laparoscopic surgery for large adnexal cysts
      with a multichannel port using a wound retractor.
AB  - This study explored and evaluated the feasibility and safety of laparoscopy with
      a multichannel port using a wound retractor for large adnexal masses. Seven
      patients scheduled to undergo single-port or 2-port laparoscopy for large adnexal
      cysts were enrolled. The cystic mass surface was exposed by inserting the wound
      retractor through the umbilical port, and cystic fluid was aspirated using a
      suction-irrigation system after puncture with an Ochsner trocar. Then,
      laparoscopic adnexal surgery was performed in the usual manner. The mean maximal
      diameter of cysts, mean operation time, and mean postoperative hospital stay were
      17.8 +/- 5.4 cm, 81.3 +/- 28.2 minutes, and 4.4 +/- 2.0 days, respectively. Use
      of multichannel ports for large adnexal cystic masses seems safe and does not
      require additional cost. The procedure is also cosmetically effective and highly
      appreciated by patients, because it results in minimal abdominal scarring.

PMID- 22874695
TI  - Laparoscopic technique for hernia reduction and mesenteric defect closure in
      patients with internal hernia as a postoperative complication of laparoscopic
      Roux-en-Y gastric bypass.
AB  - Internal hernia is a relatively common complication of laparoscopic Roux-en-Y
      gastric bypass. Laparoscopic treatment may be a challenge for nonbariatric
      surgeons if small-bowel obstruction is present. The aim of this paper is to
      present a systematic laparoscopic technique for hernia reduction and mesenteric
      defect closure in patients with small-bowel obstruction due to an internal hernia
      as a postoperative complication of laparoscopic Roux-en-Y gastric bypass. From
      February 2007 to May 2011, this technique was used in 41 consecutive patients.
      One case was converted to an open approach due to extensive bowel necrosis. There
      were no complications related to the technique but 2 patients suffered pulmonary
      aspiration during anesthesia. After the internal hernia repair patients reported
      no further abdominal symptoms. Treatment of small-bowel obstruction due to an
      internal hernia should be attempted by laparoscopy except in the setting of bowel
      necrosis. The technique presented in this article represents a safe and effective
      option for the management of this complication.

PMID- 22874696
TI  - Application of marionette technique for 3-port laparoscopic liver resection.
AB  - BACKGROUND: Laparoscopic liver resection has become a feasible and safe procedure
      for liver tumor, but it requires experienced surgeons in the case of
      hepatobiliary and laparoscopic surgeries. More minimally invasive laparoscopic
      techniques of liver surgery are developed. We here report our experience of using
      a marionette technique for 3-port laparoscopic liver resection. METHODS: Between
      June 2009 and December 2010, 7 patients underwent 3-port laparoscopic liver
      resection with the use of marionette technique. Five patients had hepatocellular
      carcinoma. Two patients with prior abdominal operations for colon cancer had
      colorectal liver metastasis. The procedure of marionette technique was performed
      as below: after insertion of the 3 trocars, a 2-0 nylon straight needle line was
      inserted through the abdominal wall, and using the needle holder, it was allowed
      to traverse the liver edge twice. Then, the straight needle line was forced out
      of the abdominal wall and clamped using mosquito for traction. Another straight
      needle line was similarly created at the opposite side of the liver edge.
      RESULTS: None of the patients had to be converted to open surgery. The mean
      operative time was 96.7 +/- 63.2 minutes (range, 45 to 195 min), and the mean
      volume of blood loss was 45.6 +/- 27.9 mL (range, 30 to 100 mL). The mean pain
      score recorded on the visual analog scale was 2.7 +/- 0.8. The mean hospital stay
      was 5.6 +/- 1.7 days (range, 4 to 9 d). Currently, all the 7 patients are alive,
      and the tumors have not recurred (Supplementary Digital Content video 1
      http://links.lww.com/SLE/A67). CONCLUSIONS: Our experience demonstrated that the
      simple marionette technique procedure could help surgeons ease laparoscopic liver
      resection and achieve better postoperative results.

PMID- 22874697
TI  - Single-incision versus conventional laparoscopic cholecystectomy: a systematic
      review of available data.
AB  - To evaluate the feasibility and limitation of single-incision laparoscopic
      cholecystectomy (SILC), we performed a systematic literature search and 11
      studies were included. SILC was successfully performed in 91.9% participants and
      conventional instruments were used mostly. Although longer operative time was
      required for this novel procedure than the conventional laparoscopic
      cholecystectomy, mean difference was 18.54 minutes (P=0.0001) and a learning
      curve was noted. There was no significant discrepancy in overall complications
      and severe complications (P=0.51 and 0.82, respectively). No difference in the
      length of hospital stay between the 2 groups was detected (P=0.09). No consensus
      has reached on the postoperative pain score between the 2 techniques. SILC with
      conventional instruments was a feasible and safe approach. It may be offered as
      an alternative for cholecystectomy in carefully selected patients.

PMID- 22874698
TI  - Robotic transaxillary central neck dissection:  video description of the
      technique.
AB  - Although various groups have described their experiences with robotic
      transaxillary thyroidectomy, to our knowledge, robotic central neck dissection
      has not been described in the North American literature. We here demonstrate the
      technique of robotic central neck dissection at the time of transaxillary total
      thyroidectomy. The procedure was performed under general anesthesia through a 6
      cm right axillary incision. The robotic camera and 2 working robotic arms were
      used for the procedure.

PMID- 22874699
TI  - Laparoscopic transhiatal resection for Siewert type II adenocarcinoma of the
      esophagogastric junction: operative technique and initial results.
AB  - Laparoscopic distal gastrectomy has gained wide acceptance, and laparoscopic
      total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG) are now also
      performed for gastric cancer. We extended these techniques to treat Siewert type
      II adenocarcinoma of the esophagogastric junction (AEG). Ten patients with
      clinical T1 AEG type II underwent laparoscopic transhiatal (LTH) resection
      combined with LTG reconstructed by Roux-en-Y (LTH+LTG: n=2) or LPG reconstructed
      by jejunal interposition (LTH+LPG: n=8). Intracorporeal esophagojejunostomy was
      performed using a circular stapler, of which the anvil head was introduced
      transabdominally or transorally. The median operation time was 243 minutes, and
      blood loss was 25.5 g. There were no intraoperative complications or conversion
      to open surgery. No anastomotic leak was observed, but 1 diaphragmatic herniation
      to the left thoracic cavity occurred postoperatively. The median length of the
      proximal margin was 14.5 mm. This operation is technically feasible and can be
      safely performed after adequate experience of LTG or LPG, though
      esophagojejunostomy in the mediastinum is technically demanding.

PMID- 22874700
TI  - Two-layer laparoscopic repair of intraperitoneal bladder rupture in blunt
      abdominal trauma: a case report with literature review.
AB  - Bladder injuries are usually reported after blunt trauma to lower abdomen. The
      pelvic fracture is associated in >80% of the cases. All intraperitoneal bladder
      tear are managed surgically with open exploration and repair. In stable patients,
      with no other intra-abdominal injury, laparoscopy acts both as a diagnostic and
      therapeutic tool. It results in faster recovery, early discharge from the
      hospital with good cosmetic outcome. We describe a similar case of
      intraperitoneal bladder rupture managed laparoscopically replicating the open
      technique of double-layer repair.

PMID- 22874701
TI  - Laparoscopic transperitoneal partial nephrectomy for renal hydatid cyst:  a case
      report.
AB  - A 29-year-old female patient with an isolated hydatid cyst in the lower pole of
      the left kidney presented with a history of weight loss and cloudy, foul-smelling
      urine. Laparoscopic partial nephrectomy was performed, at which the cyst was
      removed en bloc. On the fifth postoperative day, she was discharged without any
      complication. Nine months postoperatively, a computed tomography scan revealed no
      recurrence of hydatidosis.

PMID- 22874702
TI  - Isolated laparoscopic caudate lobe resection.
AB  - The local anatomy of the caudate lobe of the liver, between the hepatic hilum and
      the inferior vena cava, presents a surgical challenge when an isolated resection
      is attempted. The video of the laparoscopic technique is presented in a 20-year
      old woman with a 60 * 40 mm lesion.

PMID- 22874703
TI  - Single-incision laparoscopy-assisted subtotal gastrectomy for intractable gastric
      ulcer: a case report.
AB  - PURPOSE: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic
      results and may be associated with decreased postoperative pain and accelerated
      recovery. Although there have been reports of cholecystectomy and appendectomy
      using SILS, there have been few reports of gastric resection with intracorporeal
      reconstruction of the digestive tract using SILS. The first single-incision
      laparoscopic gastrectomy with intracorporeal reconstruction is reported. METHODS:
      Preliminary experience with single-incision laparoscopic gastrectomy with
      intracorporeal reconstruction for a patient with an intractable gastric ulcer is
      reported. RESULTS: Single-incision laparoscopy-assisted subtotal gastrectomy and
      Roux-en-Y reconstruction were performed. Operative time for gastrectomy and
      paraduodenal hernioplasty was 412 minutes, and blood loss was 90 g. No
      intraoperative or postoperative complications developed. CONCLUSIONS: Single
      incision laparoscopy-assisted gastrectomy for intractable gastric ulcer is
      technically feasible. Intracorporeal reconstruction of the digestive tract was
      performed safely using a linear endoscopic stapler. This surgical approach is a
      further advance toward scarless surgery of the stomach.

PMID- 22874704
TI  - Single-port laparoscopic distal gastrectomy with D1+beta lymph node dissection
      for gastric cancers: report of 2 cases.
AB  - The use of single-port laparoscopic surgery for treating various diseases has
      increased rapidly. This approach can offer better cosmetic results and less
      incisional pain. We report the cases of single-port laparoscopic distal
      gastrectomy with D1+beta lymph node dissection for 2 patients with gastric
      cancers.

PMID- 22874705
TI  - Single-port laparoscopic adhesiolysis for torsion ileus.
AB  - Single-incisional laparoscopic surgery (SILS) has emerged as an attempt to
      further enhance the cosmetic benefits and reduce the morbidity of minimally
      invasive surgery. We present an approach of SILS adhesiolysis to adhesive
      strangulated ileus. A 70-year-old female patient, who had undergone laparoscopic
      low anterior resection 6 years before, underwent SILS adhesiolysis to a midline
      surgical incision wound adhesion site. The surgery was performed with only a 2.5
      cm left-side transrectus incision using the SILS port. Laparoscopy revealed
      intestinal torsion and congestion with adhesion of the ileum to the previous
      surgical incision wound. SILS adhesiolysis was successfully carried out. The
      patient was discharged 4 days after surgery. SILS adhesiolysis is a feasible and
      efficient procedure in certain cases.

PMID- 22874706
TI  - A retained foreign body mimicking colon cancer.
AB  - Retained foreign bodies can be a challenging diagnosis due to the wide array of
      presentations and greatly varied range of time to detection. Here we report a
      case of a retained surgical sponge detected 5 years postoperatively after an
      extensive workup for colon cancer. This case demonstrates the novel finding of a
      retained surgical sponge appearing as colon cancer and serves as a reminder that
      symptoms that cannot be explained by a standard workup, in any patient who has
      undergone previous surgery, must have retained surgical instruments as a
      differential diagnosis.

PMID- 22874707
TI  - Complications of mesh repair in hiatal surgery:  about 3 cases and review of the
      literature.
AB  - Primary repair of large hiatal hernia is associated with high recurrence rate.
      The use of prosthetic mesh to reinforce the cure seems to lead to less
      recurrence. Unfortunately, this procedure is still controversial in regard of the
      possible complications that may occur. We report here 3 cases of complications
      related to mesh placement in hiatal hernia surgery: an esophageal perforation, an
      intragastric migration, and a fundic erosion. When a patient complains of
      epigastric pain or dysphagia with no peritoneal signs, in the postoperative
      course of mesh placement, an upper endoscopy should be achieved to rule out those
      complications. The patient must be informed about the mesh placement and he must
      notify the endoscopist in case of an upper gastrointestinal endoscopy.

PMID- 22874708
TI  - Endoscopic submucosal dissection combined with endoscopic injection sclerotherapy
      for early gastric cancer on gastric fundal varices.
AB  - Currently, there is little report of treatment strategy for early gastric cancer
      (EGC) on gastric fundal varices (GFVs), because controlling GFVs was more
      challenging than controlling gastric cardiac varices associated with esophageal
      varices. We first report effective endoscopic treatment of EGC on GFVs of a 77
      year-old man with Child-B cirrhosis. Endoscopic ultrasound and multidetector-row
      computed tomography studies revealed intramucosal EGC on variceal components,
      supplied from posterior gastric vein and drained to subphrenic vein without
      gastrorenal shunt. With informed consent, we performed endoscopic submucosal
      dissection (ESD) after eradication of GFVs by endoscopic injection sclerotherapy
      (EIS). Histologic assessment revealed curability of ESD and inflammation and
      fibrosis around EIS site. Thereafter, no recurrence and complication had
      occurred. To avoid life-threatening bleeding from GFVs, we achieved complete
      resection by ESD under direct visualization of submucosa after eradication of
      GFVs by EIS based on the examination of hemodynamics and local relationship
      between EGC and GFVs.

PMID- 22874709
TI  - Unique presentation of Meckel diverticulum in the form of cocoon managed
      successfully by laparoscopic surgery.
AB  - We report a case of complicated Meckel diverticulum presenting with subacute
      intestinal obstruction in a 21-year-old man managed successfully by laparoscopic
      surgery. Despite a diagnostic laparoscopy and laparotomy performed elsewhere in
      the past, main pathology was missed. Diagnostic laparoscopy in our center
      revealed a fusiform mass arising from terminal ileum, which was treated by
      laparoscopic-assisted resection and end-to-end ileo-ileal anastomosis. Gross and
      microscopic examination revealed an encapsulated localized cocoon containing 40
      cm of ileum entangled around an inflamed Meckel diverticulum. His intestinal
      obstruction and hematochezia got relieved.

PMID- 22874710
TI  - Retrograde submucosal tunneling technique for management of complete esophageal
      obstruction.
AB  - Complete esophageal obstruction is a challenging problem that is not amendable to
      standard dilation techniques. Multiple endoscopic techniques as well as radical
      surgical procedures have been developed with the goal of restoring a patent
      esophageal lumen. In patients with complete esophageal obstruction, an antegrade
      retrograde technique has been described, but this generally depends on the
      ability to transilluminate across the stricture. Successful transillumination
      allows for safe direct puncture across the stricture, followed by dilation. In
      long-segment strictures (greater than 2-3 cm), transillumination may not be
      possible. We report a case of a 63 year-old woman who developed a complete
      esophageal obstruction from radiation therapy (RT) for hypopharyngeal squamous
      cell carcinoma. She did have enteral access via a percutaneous endoscopic
      gastrostomy (PEG) tube which had been placed prior to beginning RT. A combined
      antegrade (through the mouth) and retrograde (through PEG site) approach was
      done, but transillumination across the stricture failed. Fluoroscopy demonstrated
      a 4 cm long stricture. The creation of a submucosal tunnel from the retrograde
      direction decreased the stricture length to 15 mm and transillumination was
      achieved. This allowed safe puncture of the stricture, placement of a guidewire,
      then successful dilation. The patient can now tolerate soft foods and maintain
      her weight. Submucosal tunneling can be used to achieve transillumination for the
      combined antegrade-retrograde approach to complete esophageal obstruction.

PMID- 22874711
TI  - EUS-guided rendezvous drainage for pancreatic duct obstruction from stenosis of
      pancreatojejunal anastomosis after pancreatoduodenostomy.
AB  - A 79-year-old man underwent pancreatoduodenectomy with Imanaga reconstruction for
      an ampullary adenocarcinoma in 2003. After that, he experienced recurrent
      pancreatitis with a suspicious stenotic pancreatojejunal anastomosis. Although
      endoscopic drainage through the pancreatojejunal anastomosis was attempted, the
      stenotic anastomosis could not be located endoscopically. Therefore,
      endosonography-guided rendezvous drainage through the anastomosis was performed,
      and endoscopic pancreatic stent placement was successfully completed. Thereafter,
      the patient did not experience any further attacks of pancreatitis.
      Endosonography-guided rendezvous drainage is a feasible treatment option for
      recurrent pancreatitis due to stenosis of pancreatojejunal anastomosis.

PMID- 22874712
TI  - Implantation at sternocleidomastoid and chest wall after endoscopic thyroid
      carcinoma surgery.
AB  - Endoscopic thyroidectomy has been widely accepted by surgeons and patients for
      less postoperative pain, faster postoperative recovery, and excellent cosmetic
      effect. However, there still existed some limitations. Here, we reported a woman
      who suffered local implantation metastasis at sternocleidomastoid and chest wall
      after endoscopic thyroid carcinoma surgery. Although the implantation after
      endoscopic surgery is uncommon, this case reminds us to use endoscopic surgery
      for thyroid diseases with caution, especially for thyroid cancer. Following
      strict endoscopic surgery indications, comprehensive preoperative evaluation,
      meticulous intraoperative surgical handling, and effective protective measures,
      the incidence of locoregional implantation or recurrence might be dramatically
      reduced.

PMID- 22874713
TI  - Treatment option in patient presenting with small bowel obstruction from
      phytobezoar at the jejunojejunal anastomosis after Roux-en-Y gastric bypass.
AB  - Bezoar is a rare cause of small bowel obstruction after Roux-en-Y gastric bypass
      (RYGB). We report the case of a 34-year-old man who developed small bowel
      obstruction secondary to a phytobezoar at the jejunojejunal anastomosis, 51/2
      years after the patient underwent RYGB for morbid obesity. The phytobezoar
      developed in the background of recurring abdominal pain. Imaging studies
      suggested complete obstruction of the alimentary limb. Laparoscopic exploration
      demonstrated complete obstruction of the alimentary and biliopancreatic limb.
      Patient had successful treatment with laparoscopic enterototomy. Six months after
      the laparoscopic removal of phytobezoar, patient remained asymptomatic.
      Phytobezoar formation must be considered in the differential diagnosis when
      postgastric bypass patients present late with obstructive symptoms. We believe
      that this is the first report of a phytobezoar obstructing at the jejunojejunal
      anastomosis after RYGB.

PMID- 22874714
TI  - Laparoscopic resection of an epidermoid cyst within an intrapancreatic accessory
      spleen:  a case report and review article.
AB  - CASE REPORT: We report a case of an epidermoid cyst within an intrapancreatic
      accessory spleen that was treated by laparoscopic excision. A 39-year-old man
      with no abdominal symptoms was incidentally found to have a cystic pancreatic
      lesion on computed tomography scan undertaken for suspected deep vein thrombosis.
      Further computed tomography and magnetic resonance imaging confirmed similar
      findings and the laparoscopic resection of the distal pancreas and spleen was
      undertaken as malignancy could not be excluded. Microscopic analysis revealed a
      well-circumscribed epidermoid cyst within a thin splenic rim in the tail of the
      pancreas. DISCUSSION: Such histologic diagnoses are extremely rare, and this is
      the 26th case report to our knowledge in English language journals. These lesions
      should be treated surgically to exclude malignancy. This is the first case
      reported in the United Kingdom and the first to be excised by pure laparoscopic
      means, which we believe provides effective and successful surgical management.

PMID- 22874715
TI  - Physical activity patterns in the French 18-74-year-old population: French
      Nutrition and Health Survey (Etude Nationale Nutrition Sante, ENNS) 2006-2007.
AB  - OBJECTIVE: To describe detailed physical activity and sedentary behaviour in
      French adults across physical activity categories. DESIGN: The French Nutrition
      and Health Survey (Etude Nationale Nutrition Sante, ENNS), conducted in 2006
      2007, was a national cross-sectional survey based on three-stage random sampling.
      The International Physical Activity Questionnaire (IPAQ) was used to classify
      participants into three physical activity categories. Time spent in a sitting
      position and time spent in front of a screen were used as markers of sedentary
      behaviour. SETTING: France. SUBJECTS: Adults (n 2971) aged 18 to 74 years were
      included. RESULTS: Overall, 29.5 % of men and 23.6 % of women were classified
      into the high-IPAQ category, while 36.1 % of men and 37.5 % of women were in the
      low-IPAQ category. For each intensity level of physical activity (vigorous
      intensity, moderate intensity or walking), the number of active days per week
      decreased from the high- to the low-IPAQ category and daily duration of physical
      activity was longer in the high-IPAQ category than in the other two categories; 6
      % of adults declared neither vigorous nor moderate nor walking activities.
      CONCLUSIONS: For most adults in the low-IPAQ category, an increasing number of
      active days per week would be sufficient to attain the moderate-IPAQ category.
      This should be taken into account in public health initiatives aimed at promoting
      physical activity.

PMID- 22874716
TI  - TSPO-specific ligand vinpocetine exerts a neuroprotective effect by suppressing
      microglial inflammation.
AB  - Vinpocetine has long been used for cerebrovascular disorders and cognitive
      impairment. Based on the evidence that the translocator protein (TSPO, 18 kDa)
      was expressed in activated microglia, while Vinpocetine was able to bind TSPO, we
      explored the role of Vinpocetine on microglia treated with lipopolysaccharide
      (LPS) and oxygen-glucose deprivation (OGD) in vitro. Our results show that both
      LPS and OGD induced the up-regulation of TSPO expression on BV-2 microglia by RT
      PCR, western blot and immunocytochemistry. Vinpocetine inhibited the production
      of nitrite oxide and inflammatory factors such as interleukin-1beta (IL-1beta),
      IL-6 and tumour necrosis factor-alpha (TNF-alpha) in BV-2 microglia, in which
      cells were treated with LPS or exposed to OGD, regardless of the time Vinpocetine
      was added. Next, we measured cell death-related molecules Akt, Junk and p38 as
      well as inflammation-related molecules nuclear factor-kappaB (NF-kappaB) and
      activator protein-1 (AP-1). Vinpocetine did not change cell death-related
      molecules, but inhibited the expression of NF-kappaB and AP-1 in LPS-stimulated
      microglia, indicating that Vinpocetine has an anti-inflammatory effect by partly
      targeting NF-kappaB/AP-1. Next, conditioned medium from Vinpocetine-treated
      microglia protected from primary neurons. As compared with in vitro, the
      administration of Vinpocetine in hypoxic mice also inhibited inflammatory
      molecules, indicating that Vinpocetine as a unique anti-inflammatory agent may be
      beneficial for the treatment of neuroinflammatory diseases.

PMID- 22874717
TI  - The forum has spoken.

PMID- 22874718
TI  - Health and Social Care Bill: health and wellbeing boards.

PMID- 22874719
TI  - Older people and laxative use: comparison between community and long-term care
      settings.
AB  - Constipation is a common problem affecting many older people's quality of life.
      The aim of the study was to describe and compare the frequency of use of laxative
      medication in Irish adults, aged 65 years and older, from the community and a
      long-term care setting. Participants (n=207) were part of the Irish ELDERMET
      project. The project aims to find out how diet and lifestyle influence, and are
      influenced by, the bacteria in the gut, and how this knowledge can be used to
      promote health in older Irish people. It has recruited over 450 people, aged 65
      and older, and will use the information gathered from the extensive proforma to
      develop recommendations, as well as functional foods/functional food ingredients
      specifically designed to promote and support health in older populations. Data
      were collected between June 2008 and April 2010 using a survey questionnaire. A
      quantitative descriptive correlational design was used. Analysis was conducted
      using PASW Statistics 18.0. Participants in long-term care received a greater
      number of both laxatives and prescribed medications than community-dwelling
      participants. Increased polypharmacy was also seen in participants taking
      laxatives, with participants in long-term care significantly (p<0.001) more
      likely to take multiple laxatives. Nurses are in a key position to develop
      proactive approaches to the prevention and treatment of constipation.

PMID- 22874721
TI  - A tormented death: end-of-life  care for people with dementia.
AB  - District nurses are often faced with difficulties when patients with dementia
      lack the capacity to express how they feel and the family has to make end-of-life
      decisions for the sufferer. Although 25% of palliative care is concerned with
      controlling physical symptoms, health professionals are sometimes faced with
      challenges when one comorbidity masks another. The GP-patient relationship is
      central to improving overall care for these vulnerable patients and there is a
      continual need for a workforce to be trained and empowered to provide care with
      precision. This article discusses the importance of correct diagnosis during end
      of-life care and makes recommendations on how this can be achieved.

PMID- 22874722
TI  - Staff motivation to prevent venous thromboembolism.

PMID- 22874723
TI  - Childhood obesity: nurses' role  in addressing the epidemic.
AB  - Obesity is a significant long-term health problem that is common among children
      and adolescents in Western countries. Being overweight or obese (extremely
      overweight) can contribute to type 2 diabetes in childhood and increase the risk
      of cardiovascular disease in adulthood. Primary prevention of obesity prevents
      the development of serious secondary complications in adulthood. Nurses can help
      parents and children by providing nutritional advice and, through weight
      management programmes, offer strategies for decreasing caloric intake and
      increasing physical activity. Nurses' actions should always take a whole-family
      approach because it is challenging for obese children to alter their dietary or
      physical habits if not supported by their families. Nurses should work with all
      members of the multidisciplinary team in addressing childhood obesity as it is a
      major health issue with long-term mobidities.

PMID- 22874724
TI  - Tuberculosis care: Olympics 1948 vs 2012.
AB  - Tuberculosis (TB) is a multi-faceted illness associated with a long and
      fascinating history. Although much has changed in the diagnosis, treatment and
      prevention of TB over the past six decades, many of the challenges remain
      remarkably similar. In developing solutions to these challenges, key stakeholders
      and politicians would do well to learn from some of the more effective strategies
      from the pre-chemotherapy era. Despite working with insufficient resources,
      nurses have historically contributed significantly to the work of the
      multidisciplinary teams in delivering care to patients and families, as well as
      in implementing national TB control and prevention programmes. The current
      resurgence of TB in the UK makes it imperative to achieve consistently and
      appropriately-funded TB services across the country. Whether NHS commissioners
      and politicians will engage with nurses and others in the reconfigured NHS to
      achieve this, however, remains to be seen.

PMID- 22874725
TI  - Safeguarding children: the benefits of a peer-review process.
AB  - Nurses in hospitals and in the community are increasingly taking a leading role
      in safeguarding children. NHS London established a Safeguarding Improvement Team
      (SIT) in 2009. The SIT project was designed as a one-off activity to raise
      performance related to safeguarding children in London. This article presents a
      peer-review process that was established by NHS London and implemented across the
      31 PCTs across London. This article presents the peer-review process methodology
      and a summary of the findings from the SIT visits. Feedback was requested from
      participants about participants' perceptions of the peer-review process
      immediately after the SIT visits and again, several months after the completion
      of all SIT visits. Findings show that the peer-review process was of value, both
      organisationally and professionally, and the process itself led to identification
      of good practice as well as gaps in existing practices. The non-threatening
      nature of the peer-review process was particularly valued, as was the feedback
      offered by the review teams.

PMID- 22874726
TI  - Recovery: a time  to listen to the patient.

PMID- 22874728
TI  - Fit to practice? The NMC surveys registrants for suggestions.

PMID- 22874729
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 2: learning
      from a text book.

PMID- 22874727
TI  - Expert review of cardiopulmonary resuscitation (CPR) in hospital.

PMID- 22874730
TI  - Keep calm and carry on:  a look at nurse resilience.

PMID- 22874731
TI  - Back pain in Portuguese schoolchildren: prevalence and risk factors.
AB  - BACKGROUND: Regarding children aged <= 10 years, only a few international studies
      were conducted to determine the prevalence of and risk factors for back pain.
      Although other studies on the older Portuguese children point to prevalence
      between 17% and 39%, none exists for this specific age-group. Thus, the aim of
      this study was conducted to establish the prevalence of and risk factors for back
      pain in schoolchildren aged 7-10 years. METHODS: A cross-sectional survey among
      637 children was conducted. A self-rating questionnaire was used to verify
      prevalence and duration of back pain, life habits, school absence, medical
      treatments or limitation of activities. For posture assessment, photographic
      records with a bio-photogrammetric analysis were used to obtain data about head,
      acromion and pelvic alignment, horizontal alignment of the scapulae, vertical
      alignment of the trunk and vertical body alignment. RESULTS: Postural problems
      were found in 25.4% of the children, especially in the 8- and 9-year-old groups.
      Back pain occurs in 12.7% with the highest values among the 7- and 10-year-old
      children. The probability of back pain increased 7 times when the children
      presented a history of school absences, 4.3 times when they experienced sleeping
      difficulties, 4.4 times when school furniture was uncomfortable, 4.7 times if the
      children perceived an occurrence of parental back pain and 2.5 times when
      children presented incorrect posture. CONCLUSIONS: The combination of school
      absences, parental pain, sleeping difficulties, inappropriate school furniture
      and postural deviations at the sagittal and frontal planes seem to prove the
      multifactorial aetiology of back pain.

PMID- 22874732
TI  - Effects of the 2010 World Cup football tournament on emergency department assault
      attendances in England.
AB  - We explore the impact of the 2010 World Cup, held in South Africa, on levels of
      assault attendances to 15 emergency departments in England. The majority (70.1%)
      of assault attendees during the 2010 World Cup was male and aged 18-34 years
      (52.5%). Assault attendances increased by 37.5% on the days that England played
      (P 001). Preparation for major sporting events in non-host countries should
      include violence prevention activity. Emergency department data can be used to
      identify violence associated with such events and thus inform both the targeting
      of prevention efforts and assessments of their effectiveness.

PMID- 22874733
TI  - Gender inequalities in the association between demands of family and domestic
      life and health in Spanish workers.
AB  - BACKGROUND: The aim of this study is to analyse gender inequalities in the
      relationship between family demands and health in working and cohabiting
      population. METHODS: A total of 9108 men and women aged 25 to 64 years who were
      employed and cohabiting were selected from the 2006 National Health Survey of
      Spain. Outcome variables were self-perceived health status, mental health, daily
      sleeping hours and leisure time sedentarism. Explanatory variables were household
      size, living with children <15 years, living with adults between 65 and 74 years,
      living with adults >74 years and having a hired person for housework.
      Multivariate logistic regression models were fitted, stratified by gender and
      social class and adjusted for age. RESULTS: Household size was related to poor
      self-perceived health status, poor mental health and leisure time sedentarism in
      both men and women manual workers. Moreover, it was also related to sleeping 6 h
      or less a day amog manual worker women. Having a hired person for housework was
      protective for self-perceived health status in both men and women. CONCLUSION:
      Family demands are mainly related to manual workers' health, among both men and
      women. Whereas the association between family demands and poor health status
      among women could be explained by their greater housework and caregiver demands
      compared with men, among men, given their role as the main breadwinner in the
      home, it could be due to financial problems. The relationship between family
      demands and health should be studied in a combined framework of gender and social
      class.

PMID- 22874734
TI  - Electronic screen use and mental well-being of 10-12-year-old children.
AB  - BACKGROUND: Today's children spend a great deal of time viewing electronic screen
      material, but the consequences of such behaviors, if any, are unknown. This study
      sought to identify (i) the magnitude of total daily electronic screen time and
      (ii) the relations between electronic screen use and mental well-being
      indicators, in a sample of 10-12-year-old children. METHODS: We analysed cross
      sectional, population-based data of 10-12-year-old children from the 2007 Youth
      in Iceland school survey (n = 10,829, response rate: 81.7%, boys: 50.5%).
      Logistic regression models with odds ratios and 95% confidence intervals were
      conducted to assess the odds of each selected mental well-being indicator,
      depending on the number of daily hours spent on each electronic screen-based
      activity. All analyses were conducted separately for boys and girls and adjusted
      for family structure. RESULTS: The prevalence of self-reported screen use of 4
      hours per day or more ranges from 2.8% to 6.6% among boys and from 1.0% to 3.8%
      among girls. All five screen-based activities were significantly associated with
      all seven well-being indicators (P < 0.001) with symptoms being more common with
      increased time spent on screen use. CONCLUSIONS: This study is the first of its
      kind to demonstrate a dose-response relationship between electronic screen use
      and mental well-being in 10-12-year-old children. Further research is needed to
      assess the validity and potential implications of these findings.

PMID- 22874735
TI  - Does life course socio-economic position influence chronic disabling pain in
      older adults? A general population study.
AB  - BACKGROUND: Chronic pain is the leading cause of disability in developed
      countries. Prevalence is linked with socio-economic position (SEP), but little is
      known about the influence of SEP on disabling pain over the life course. We have
      investigated the influence of different life course trajectories of SEP on
      disabling pain ('pain interference') in postal surveys of adults aged >=50 years
      sampled from the general population of adults registered with three UK general
      practices. METHODS: Current pain interference was measured using the dichotomized
      36-item Short-Form (SF-36) health survey. Three recalled SEP measures (age left
      school, longest job and current/most recent job) were dichotomized into low SEP
      (left school at or before minimum school leaving age; reported routine or manual
      occupations) and high SEP, from which eight life course SEP trajectories were
      constructed. Associations of (i) eight SEP trajectories and (ii) three individual
      SEP measures adjusted for each other, with pain interference, adjusted for
      potential confounders, were calculated using logistic regression. RESULTS: A
      total of 2533 individuals provided data on all three SEP measures. A consistently
      low life course SEP trajectory was significantly associated with current pain
      interference compared with a high trajectory [odds ratio (OR) = 2.76, 95%
      confidence interval (CI): 2.19-3.47], even after adjustment for age and gender.
      Further adjustment reduced the association but it remained significant (OR =
      2.04; 95% CI: 1.55-2.68). In the model with individual measures, low age left
      school (OR = 1.45; 95% CI: 1.15-1.82) and manual longest job (OR = 1.47; 95% CI:
      1.13-1.91) were independently associated with pain interference. CONCLUSIONS: Our
      results highlight the potential for reducing chronic disabling pain in later life
      by addressing inequalities in both childhood education and adult occupational
      opportunities.

PMID- 22874736
TI  - Mammography use for breast cancer screening in Portugal: results from the
      2005/2006 National Health Survey.
AB  - BACKGROUND: Understanding the patterns of mammography use is essential to promote
      the participation in breast cancer screening. OBJECTIVES: To describe the
      patterns of screening mammography use in Portugal. METHODS: As part of the fourth
      National Health Survey (2005/2006), 3045 women were evaluated in face-to-face
      interviews. The previous use of mammography for screening was classified as never
      or ever, and the latter was further grouped according to the time elapsed since
      the latest mammography. Having undergone the latest mammography >2 years before
      was considered underuse. We assessed the determinants of never having been
      screened by mammography and, among those who had been tested, the determinants of
      mammography underuse, through age- and education-adjusted odds ratios (ORs), with
      95% confidence intervals (95% CIs). RESULTS: Among women aged 45-49 and 50-69
      years, 86.3% and 88.0%, respectively, underwent a screening mammography before,
      and most of them were tested in the previous 2 years. The lowest risk of never
      having been screened was in Norte (OR = 0.41, 95% CI: 0.21-0.80) and the highest
      in Acores (OR = 4.04, 95% CI: 2.37-6.92), in comparison with Centro (the region
      with organized screening for a longer time). Participants with <4 years of formal
      education were more likely to have never been screened than the more educated (OR
      = 4.27, 95% CI: 1.67-10.89). Women with private health insurance (OR = 0.16, 95%
      CI: 0.04-0.65), as well as those who had undergone cervical cytology screening
      before (OR = 0.50, 95% CI: 0.30-0.85), had a lower risk of underuse. CONCLUSIONS:
      This study provides useful information to improve the allocation of resources to
      breast cancer screening.

PMID- 22874737
TI  - Two decades of inequalities in smoking prevalence, initiation and cessation in a
      southern European region: 1986-2007.
AB  - BACKGROUND: The smoking epidemic is still progressing in southern Europe. We
      aimed to analyse the magnitude and trend of social inequalities in smoking
      prevalence, initiation and cessation in the Basque Country, a southern European
      region, from 1986 to 2007, determining the patterns by sex and age. METHODS: This
      was a cross-sectional time trend study on the population aged >24 years using the
      Basque Country Health Surveys of 1986, 1992, 1997, 2002 and 2007. Age-adjusted
      prevalence of current and ever smoking and cessation were calculated, as were
      relative index of inequality and population-attributable risk by occupational
      social class and educational level. Relative risk of starting smoking was
      estimated using Cox proportional hazard regression models. Calculations were
      performed separately by sex and for two age groups (25-44 years and >44 years).
      RESULTS: Men and young women in the Basque Country have evolved towards the last
      stage of the epidemic, with an increasing concentration of smoking in
      disadvantaged groups, by educational level, especially among the youngest
      population. In older women, smoking continues rising, especially among higher
      socio-economic groups, though differences between groups are diminishing. The
      role of initiation and cessation inequalities as determinants of smoking
      inequalities differed considerably by age and sex. CONCLUSION: Inequalities in
      smoking prevalence widened from 1986 to 2007 in the Basque Country, especially
      among the youngest population. The changing pattern of these inequalities and the
      different roles of initiation and cessation dynamics need to be taken into
      account to improve the results of tobacco control policies and their effect on
      smoking inequalities.

PMID- 22874738
TI  - Factors associated with delayed tuberculosis diagnosis in China.
AB  - BACKGROUND: Delays in the diagnosis of tuberculosis reflect a lack of access to
      care, and contribute to ongoing tuberculosis transmission in the community. The
      objective of this study was to evaluate the delay in tuberculosis testing and the
      associated risk factors in Shanghai, Shandong and Sichuan provinces in China.
      METHODS: A prospective cohort study of 765 culture-positive pulmonary
      tuberculosis patients registered between December 2006 and December 2008. The
      delay between the onset of symptoms and tuberculosis diagnosis testing and
      patient information were recorded in a questionnaire and analysed. RESULTS: The
      median delay was 36 days and was significantly shorter in patients from Shanghai
      compared with other places (30 vs. 42 days, P < 0.001). Multivariate analysis
      revealed that cough in Shanghai patients, lowest income level, being married and
      presenting expectoration in Shandong and Sichuan patients, were associated with a
      delay in the diagnosis testing of tuberculosis of >30 days. The only factor
      associated with a delay of >90 days was, in Shandong and Sichuan provinces only,
      female gender. The presence of other pulmonary symptoms like haemoptysis and loss
      of weight, fever and chills could shorten these delays. CONCLUSION: Efforts to
      shorten delays in the diagnosis of tuberculosis must target vulnerable
      populations. The non-specific symptom of cough is a risk factor associated with
      longer delays. Training for healthcare workers in areas with a high incidence of
      tuberculosis, where a delayed diagnosis in coughers may enhance tuberculosis
      transmission in the community, is of paramount importance.

PMID- 22874740
TI  - Rotational thromboelastometry analysis and management of life-threatening
      haemorrhage in isolated craniofacial injury.
AB  - Massive haemorrhage from facial fractures is rare but the associated mortality
      rate is high. Here, we describe a case in which thromboelastometry [rotational
      thromboelastometry (ROTEM)]-guided administration of prothrombin complex
      concentrate and fibrinogen concentrate was effective in correcting coagulopathy
      in a 68-year-old man with serious craniofacial trauma and massive haemorrhage.
      The patient, a cyclist who collided with a car, was transferred to the emergency
      department of our hospital with signs of shock and significant bleeding from
      multiple fractures and soft tissue injuries to the face. Blood gas analysis and
      standard laboratory tests revealed the presence of anaemia and acidosis, and our
      massive haemorrhage protocol was initiated. E-FAST and total-body computed
      tomography scans excluded the possibility of bleeding from other sites. All
      efforts were directed towards stopping bleeding from craniofacial lesions, but
      the surgeon experienced difficulty in maintaining haemostasis. ROTEM analysis
      revealed severe coagulopathy and was indispensable in guiding transfusion: 2 g
      tranexamic acid, followed by 1000 IU prothrombin complex concentrate, 5 g
      fibrinogen and 2 U platelet concentrate. Two hours later, ROTEM analysis showed
      that coagulopathy had been corrected, and haemostasis was confirmed by cessation
      of bleeding. This report highlights the potential for using ROTEM to guide
      treatment with fibrinogen and prothrombin complex concentrates in the presence of
      profuse multifocal bleeding and severe coagulopathy.

PMID- 22874741
TI  - Letter to the Editor regarding 'effect of rivaroxaban, in contrast to heparin, is
      similar in neonatal and adult plasma'.

PMID- 22874742
TI  - Prophylactic administration of fibrinogen concentrate in a pregnant woman with
      congenital hypofibrinogenemia and a positive obstetric history of severe bleeding
      in previous cesarean section.

PMID- 22874743
TI  - Anaphylaxis with tissue plasminogen activator:  case report and literature
      review.

PMID- 22874744
TI  - Glycosylation influences the stability of human plasminogen activator inhibitor
      1.

PMID- 22874745
TI  - Discard tube for coagulation testing:  the debate continues.

PMID- 22874746
TI  - Intercommunity effects on microbiome and GpSGHV density regulation in tsetse
      flies.
AB  - Tsetse flies have a highly regulated and defined microbial fauna made of 3
      bacterial symbionts (obligate Wigglesworthia glossinidia, commensal Sodalis
      glossinidius and parasitic Wolbachia pipientis) in addition to a DNA virus
      (Glossina pallidipes Salivary gland Hypertrophy Virus, GpSGHV). It has been
      possible to rear flies in the absence of either Wigglesworthia or in totally
      aposymbiotic state by dietary supplementation of tsetse's bloodmeal. In the
      absence of Wigglesworthia, tsetse females are sterile, and adult progeny are
      immune compromised. The functional contributions for Sodalist are less known,
      while Wolbachia cause reproductive manupulations known as cytoplasmic
      incompatibility (CI). High GpSGHV virus titers result in reduced fecundity and
      lifespan, and have compromised efforts to colonize flies in the insectary for
      large rearing purposes. Here we investigated the within community effects on the
      density regulation of the individual microbiome partners in tsetse lines with
      different symbiotic compositions. We show that absence of Wigglesworthia results
      in loss of Sodalis in subsequent generations possibly due to nutritional
      dependancies between the symbiotic partners. While an initial decrease in
      Wolbachia and GpSGHV levels are also noted in the absence of Wigglesworthia,
      these infections eventually reach homeostatic levels indicating adaptations to
      the new host immune environment or nutritional ecology. Absence of all bacterial
      symbionts also results in an initial reduction of viral titers, which recover in
      the second generation. Our findings suggest that in addition to the host immune
      system, interdependencies between symbiotic partners result in a highly tuned
      density regulation for tsetse's microbiome.

PMID- 22874747
TI  - Coming out of the starting blocks: extended lag time rearranges genetic diversity
      in introduced marine fishes of Hawai'i.
AB  - Biological invasions with known histories are rare, especially in the sea, and
      empirical studies of the genetic consequences are even rarer. Fifty-five years
      ago, the state of Hawai'i began a remarkable, if unintentional, 'experiment' with
      the introduction of three reef fishes, Lutjanus fulvus, Cephalopholis argus and
      Lutjanus kasmira. All have since expanded from the initial introduction of 2204
      to 3163 individuals; however, historical records show that initially L. fulvus
      remained scarce, C. argus had modest population expansion and L. kasmira
      experienced rapid population growth. The consequences of differential population
      growth rates are apparent in F-statistics: Hawaiian L. fulvus demonstrate strong
      and significant haplotype frequency shifts from the founder location (F(ST) =
      0.449), C. argus shows low but significant differentiation (F(ST) = 0.066) and L.
      kasmira is nearly identical to the founder location (F(ST) = 0.008). All three
      species had higher mtDNA diversity in the introduced range, which can be
      explained by multiple sources for L. fulvus and L. kasmira, but not for C. argus.
      We conclude that lag time before population expansion, in conjunction with
      genetic drift, has defined the genetic architecture of these three species in the
      introduced range.

PMID- 22874748
TI  - Innovative problem solving by wild spotted hyenas.
AB  - Innovative animals are those able to solve novel problems or invent novel
      solutions to existing problems. Despite the important ecological and evolutionary
      consequences of innovation, we still know very little about the traits that vary
      among individuals within a species to make them more or less innovative. Here we
      examine innovative problem solving by spotted hyenas (Crocuta crocuta) in their
      natural habitat, and demonstrate for the first time in a non-human animal that
      those individuals exhibiting a greater diversity of initial exploratory
      behaviours are more successful problem solvers. Additionally, as in earlier work,
      we found that neophobia was a critical inhibitor of problem-solving success.
      Interestingly, although juveniles and adults were equally successful in solving
      the problem, juveniles were significantly more diverse in their initial
      exploratory behaviours, more persistent and less neophobic than were adults. We
      found no significant effects of social rank or sex on success, the diversity of
      initial exploratory behaviours, behavioural persistence or neophobia. Our results
      suggest that the diversity of initial exploratory behaviours, akin to some
      measures of human creativity, is an important, but largely overlooked,
      determinant of problem-solving success in non-human animals.

PMID- 22874749
TI  - Visual accommodation and active pursuit of prey underwater in a plunge-diving
      bird: the Australasian gannet.
AB  - Australasian gannets (Morus serrator), like many other seabird species, locate
      pelagic prey from the air and perform rapid plunge dives for their capture. Prey
      are captured underwater either in the momentum (M) phase of the dive while
      descending through the water column, or the wing flapping (WF) phase while
      moving, using the wings for propulsion. Detection of prey from the air is clearly
      visually guided, but it remains unknown whether plunge diving birds also use
      vision in the underwater phase of the dive. Here we address the question of
      whether gannets are capable of visually accommodating in the transition from
      aerial to aquatic vision, and analyse underwater video footage for evidence that
      gannets use vision in the aquatic phases of hunting. Photokeratometry and
      infrared video photorefraction revealed that, immediately upon submergence of the
      head, gannet eyes accommodate and overcome the loss of greater than 45 D
      (dioptres) of corneal refractive power which occurs in the transition between air
      and water. Analyses of underwater video showed the highest prey capture rates
      during WF phase when gannets actively pursue individual fish, a behaviour that
      very likely involves visual guidance, following the transition after the plunge
      dive's M phase. This is to our knowledge the first demonstration of the capacity
      for visual accommodation underwater in a plunge diving bird while capturing
      submerged prey detected from the air.

PMID- 22874750
TI  - Precise RNAi-mediated silencing of metabolically active proteins in the defence
      secretions of juvenile leaf beetles.
AB  - Allomones are widely used by insects to impede predation. Frequently these
      chemical stimuli are released from specialized glands. The larvae of Chrysomelina
      leaf beetles produce allomones in gland reservoirs into which the required
      precursors and also the enzymes are secreted from attached gland cells. Hence,
      the reservoirs can be considered as closed bio-reactors for producing defensive
      secretions. We used RNA interference (RNAi) to analyse in vivo functions of
      proteins in biosynthetic pathways occurring in insect secretions. After a salicyl
      alcohol oxidase was silenced in juveniles of the poplar leaf beetles, Chrysomela
      populi, the precursor salicyl alcohol increased to 98 per cent, while salicyl
      aldehyde was reduced to 2 per cent within 5 days. By analogy, we have silenced a
      novel protein annotated as a member of the juvenile hormone-binding protein
      superfamily in the juvenile defensive glands of the related mustard leaf beetle,
      Phaedon cochleariae. The protein is associated with the cyclization of 8
      oxogeranial to iridoids (methylcyclopentanoid monoterpenes) in the larval
      exudates made clear by the accumulation of the acylic precursor 5 days after RNAi
      triggering. A similar cyclization reaction produces the secologanin part of
      indole alkaloids in plants.

PMID- 22874751
TI  - Offspring fitness varies with parental extra-pair status in song sparrows,
      Melospiza melodia.
AB  - Numerous studies have tested for indirect selection on female extra-pair
      reproduction (EPR) by quantifying whether extra-pair young (EPY) are fitter than
      their within-pair young (WPY) maternal half-siblings. In contrast, the hypothesis
      that offspring of EPY and WPY (rather than the EPY and WPY themselves) differ in
      fitness has not been tested, even though inter-generational effects of parental
      extra-pair status on offspring fitness could alter the magnitude and direction of
      indirect selection on EPR. We tested whether offspring of EPY song sparrows,
      Melospiza melodia, were more likely to recruit or produce hatched or recruited
      offspring over their lifetimes than offspring of WPY. Hatchlings with one or two
      EPY parents were more likely to recruit and produce hatched offspring than
      hatchlings with two WPY parents. Furthermore, these relationships differed
      between maternal versus paternal extra-pair status. Hatchlings with EPY fathers
      were more likely to recruit and produce offspring than hatchlings with WPY
      fathers. In contrast, hatchlings with EPY mothers were as likely to recruit as
      hatchlings with WPY mothers and tended to be less likely to produce recruited
      offspring. Depending on the causal genetic and environmental mechanisms, such
      conflicting inter-generational relationships between parental extra-pair status
      and offspring fitness could substantially influence the evolutionary dynamics of
      EPR.

PMID- 22874752
TI  - Life histories and the evolution of cooperative breeding in mammals.
AB  - While the evolution of cooperative breeding systems (where non-breeding helpers
      participate in rearing young produced by dominant females) has been restricted to
      lineages with socially monogamous mating systems where coefficients of
      relatedness between group members are usually high, not all monogamous lineages
      have produced species with cooperative breeding systems, suggesting that other
      factors constrain the evolution of cooperative breeding. Previous studies have
      suggested that life-history parameters, including longevity, may constrain the
      evolution of cooperative breeding. Here, we show that transitions to cooperative
      breeding across the mammalian phylogeny have been restricted to lineages where
      females produce multiple offspring per birth. We find no support for effects of
      longevity or of other life-history parameters. We suggest that the evolution of
      cooperative breeding has been restricted to monogamous lineages where helpers
      have the potential to increase the reproductive output of breeders.

PMID- 22874753
TI  - Grey parrots use inferential reasoning based on acoustic cues alone.
AB  - Our ability to make logical inferences is considered as one of the cornerstones
      of human intelligence, fuelling investigations of reasoning abilities in non
      human animals. Yet, the evidence to date is equivocal, with apes as the prime
      candidates to possess these skills. For instance, in a two-choice task, apes can
      identify the location of hidden food if it is indicated by a rattling noise
      caused by the shaking of a baited container. More importantly, they also use the
      absence of noise during the shaking of the empty container to infer that this
      container is not baited. However, since the inaugural report of apes solving this
      task, to the best of our knowledge, no comparable evidence could be found in any
      other tested species such as monkeys and dogs. Here, we report the first
      successful and instantaneous solution of the shaking task through logical
      inference by a non-ape species, the African grey parrot. Surprisingly, the
      performance of the birds was sensitive to the shaking movement: they were
      successful with containers shaken horizontally, but not with vertical shaking
      resembling parrot head-bobbing. Thus, grey parrots seem to possess ape-like cross
      modal reasoning skills, but their reliance on these abilities is influenced by
      low-level interferences.

PMID- 22874754
TI  - The island-mainland species turnover relationship.
AB  - Many oceanic islands are notable for their high endemism, suggesting that islands
      may promote unique assembly processes. However, mainland assemblages sometimes
      harbour comparable levels of endemism, suggesting that island biotas may not be
      as unique as is often assumed. Here, we test the uniqueness of island biotic
      assembly by comparing the rate of species turnover among islands and the
      mainland, after accounting for distance decay and environmental gradients. We
      modelled species turnover as a function of geographical and environmental
      distance for mainland (M-M) communities of Anolis lizards and Terrarana frogs,
      two clades that have diversified extensively on Caribbean islands and the
      mainland Neotropics. We compared mainland-island (M-I) and island-island (I-I)
      species turnover with predictions of the M-M model. If island assembly is not
      unique, then the M-M model should successfully predict M-I and I-I turnover,
      given geographical and environmental distance. We found that M-I turnover and, to
      a lesser extent, I-I turnover were significantly higher than predicted for both
      clades. Thus, in the first quantitative comparison of mainland-island species
      turnover, we confirm the long-held but untested assumption that island
      assemblages accumulate biodiversity differently than their mainland counterparts.

PMID- 22874755
TI  - Food security and climate change: on the potential to adapt global crop
      production by active selection to rising atmospheric carbon dioxide.
AB  - Agricultural production is under increasing pressure by global anthropogenic
      changes, including rising population, diversion of cereals to biofuels, increased
      protein demands and climatic extremes. Because of the immediate and dynamic
      nature of these changes, adaptation measures are urgently needed to ensure both
      the stability and continued increase of the global food supply. Although
      potential adaption options often consider regional or sectoral variations of
      existing risk management (e.g. earlier planting dates, choice of crop), there may
      be a global-centric strategy for increasing productivity. In spite of the
      recognition that atmospheric carbon dioxide (CO(2)) is an essential plant
      resource that has increased globally by approximately 25 per cent since 1959,
      efforts to increase the biological conversion of atmospheric CO(2) to stimulate
      seed yield through crop selection is not generally recognized as an effective
      adaptation measure. In this review, we challenge that viewpoint through an
      assessment of existing studies on CO(2) and intraspecific variability to
      illustrate the potential biological basis for differential plant response among
      crop lines and demonstrate that while technical hurdles remain, active selection
      and breeding for CO(2) responsiveness among cereal varieties may provide one of
      the simplest and direct strategies for increasing global yields and maintaining
      food security with anthropogenic change.

PMID- 22874756
TI  - Underwater locomotion in a terrestrial beetle: combination of surface de-wetting
      and capillary forces.
AB  - For the first time, we report the remarkable ability of the terrestrial leaf
      beetle Gastrophysa viridula to walk on solid substrates under water. These
      beetles have adhesive setae on their feet that produce a secretory fluid having a
      crucial role in adhesion on land. In air, adhesion is produced by capillary
      forces between the fluid-covered setae and the substrate. In general, capillary
      forces do not contribute to adhesion under water. However, our observations
      showed that these beetles may use air bubbles trapped between their adhesive
      setae to walk on flooded, inclined substrata or even under water. Beetle adhesion
      to hydrophilic surfaces under water was lower than that in air, whereas adhesion
      to hydrophobic surfaces under water was comparable to that in air. Oil-covered
      hairy pads had a pinning effect, retaining the air bubbles on their feet. Bubbles
      in contact with the hydrophobic substrate de-wetted the substrate and produced
      capillary adhesion. Additional capillary forces are generated by the pad's liquid
      bridges between the foot and the substrate. Inspired by this idea, we designed an
      artificial silicone polymer structure with underwater adhesive properties.

PMID- 22874757
TI  - Diagnosis of Kyasanur forest disease by nested RT-PCR, real-time RT-PCR and IgM
      capture ELISA.
AB  - Kyasanur forest disease (KFD) is a zoonotic viral disease caused by infection by
      a Flavivirus, a member of the family Flaviviridae. KFD is a public health concern
      in the Karnataka State in southern India. Available conventional diagnostic tests
      such as virus isolation and serological tests, such as haemagglutination
      inhibition and complement fixation tests are time consuming. This study reports
      the development of a nested RT-PCR [nRT-PCR] and a TaqMan-based real-time RT-PCR
      and IgM antibodies capture ELISA [MAC-ELISA] for rapid and accurate diagnosis of
      suspected KFD cases. The nRT-PCR and the TaqMan-based real-time RT-PCR assays
      were developed using gene sequences of the NS-5/non-coding region. Both the
      assays detected KFD viral RNA in acute phase human serum samples and can provide
      early diagnosis of infection. Real-time RT-PCR was found to be more sensitive
      than nRT-PCR, which could detect 38 copies of KFDV RNA. MAC-ELISA was developed
      for the detection of recent infections. Although real-time RT-PCR and nRT-PCR
      require expensive reagents, expensive equipment and trained personnel, the
      developed MAC-ELISA can be used easily in the affected areas. These tests add to
      the existing diagnosis arsenal against haemorrhagic viruses that are prevalent in
      India. These assays will also help to extend our knowledge of the pathology of
      KFD virus and its associated clinical features, by measuring the viral titre
      during infection and at the time of seroconversion. Information, which is not
      available currently because of the lack of appropriate diagnostic methods. In
      addition, early laboratory diagnosis of KFDV infection will help in the
      application of appropriate control measures and management of KFD cases.

PMID- 22874758
TI  - Reaction specificities of the epsilon-ionone-forming lycopene cyclase from rice
      (Oryza sativa) elucidated in vitro.
AB  - Lycopene cyclases responsible for the formation of epsilon-ionone rings (LCYe)
      mark a plant-specific bifurcation of carotenogenesis. We investigated purified
      rice LCYe (OsLCYe) in a liposome-based biphasic assay system. OsLCYe depends on
      reduced flavin cofactors stabilizing a transient state formed during the non
      redox cyclization reaction. In contrast to OsLCYb, OsLCYe produces predominantly
      monocyclic products and monocyclic carotene intermediates are not suitable
      substrates. Determination of the OsLCYe reaction specificities and the combined
      use of OsLCYb allow the characterization of the reaction sequence leading to
      heterocyclic carotenoids. It was also found that 5-cis-lycopene, which was
      thought to be decisive for epsilon-cyclization, was not involved in the reaction,
      with OsLCYe acting as an exclusion filter for this naturally occurring isomer.

PMID- 22874759
TI  - Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats.
AB  - Proteinuria is considered to play an essential role in the progression of
      tubulointerstitial damage, which causes end-stage renal disease. Fatty acid
      binding albumins are filtered through glomeruli and reabsorbed into proximal
      tubular epithelial cells (PTECs). However, the role of fatty acid metabolism
      associated with albuminuria in the development of tubulointerstitial damage
      remains unclear. Thus, the present study was designed to determine the changes of
      fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome,
      Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited
      hypoalbuminemia were treated with a single injection of puromycin aminonucleoside
      (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and
      caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the
      enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA
      dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in
      PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated
      receptor (PPAR)-gamma coactivator (PGC)-1alpha and estrogen-related receptor
      (ERR)alpha also significantly decreased, without changes in the expression of
      PPAR-alpha. In NARs, PAN treatment induced proteinuria but not albuminuria and
      did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of
      MCAD, PGC-1alpha, or ERRalpha did not change in the kidney cortex of PAN-treated
      NARs, but the expression of CYP4A significantly decreased. These results indicate
      that massive albuminuria causes tubular damage and lipid accumulation with the
      reduction of MCAD, CYP4A, PGC-1alpha, and ERRalpha in PTECs.

PMID- 22874760
TI  - Role of A1 receptors in renal sympathetic neurotransmission in the mouse kidney.
AB  - A(1) receptors may participate in renal sympathetic neurotransmission by
      enhancing the postjunctional effects of norepinephrine. The purpose of this study
      was to test this concept using A(1) receptor knockout (A(1)AR-/-) mice. In
      isolated kidneys from nontransgenic mice perfused with Tyrode's solution at a
      constant rate, renal sympathetic nerve stimulation (RSNS) increased (P < 0.0001)
      renal venous perfusate levels of inosine (adenosine metabolite) from 23.9 +/- 3.7
      to 32.7 +/- 5.1, 68.2 +/- 12.4, and 94.0 +/- 14.3 ng/ml at 3, 5, and 7 Hz,
      respectively (n = 28), suggesting frequency-dependent production of adenosine.
      Conversely, RSNS decreased (P < 0.0001) renal venous perfusate levels of 5'-AMP
      (adenosine precursor) from 1.4 +/- 0.3 to 1.1 +/- 0.3, 0.80 +/- 0.2, and 0.6 +/-
      0.2 ng/ml at 3, 5, and 7 Hz, respectively (n = 28), suggesting frequency
      dependent increased metabolism of 5'-AMP. In kidneys from nontransgenic mice,
      blockade of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine
      attenuated (P = 0.0130) vasoconstrictor responses to RSNS at 3, 5, and 7 Hz
      [control (n = 29): 22 +/- 4, 34 +/- 6, 42 +/- 6 mmHg, respectively; 1,3-dipropyl
      8-p-sulfophenylxanthine-treated (n = 11): 6 +/- 1, 12 +/- 3, 15 +/- 3 mmHg,
      respectively]. In A(1)AR-/- kidneys (n = 10), vasoconstrictor responses to RSNS
      at 3, 5, and 7 Hz were 7 +/- 3, 20 +/- 5, and 36 +/- 9 mmHg, respectively. In
      kidneys from wild-type littermates (n = 9), responses were 27 +/- 9, 58 +/- 14,
      and 59 +/- 11 mmHg, respectively (effect of genotype: P = 0.0363). In kidneys
      from nontransgenic mice, 2-chloro-N(6)-cyclopentyladenosine (CCPA; highly
      selective A(1) receptor agonist) increased renal vasoconstriction induced by
      norepinephrine (P = 0.0008; n = 28). In kidneys from A(1)AR-/- the response to
      norepinephrine was attenuated and the ability of CCPA to enhance responses to
      norepinephrine was abolished. In conclusion, adenosine formed during RSNS
      enhances the postjunctional effects of released norepinephrine by activating A(1)
      receptors.

PMID- 22874761
TI  - Impact of the cystic fibrosis mutation F508del-CFTR on renal cyst formation and
      growth.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis
      transmembrane conductance regulator (CFTR), the protein product of the gene
      defective in cystic fibrosis (CF), plays a crucial role in fluid accumulation,
      which promotes cyst swelling. Several studies have identified individuals
      afflicted by both ADPKD and CF. Two studies suggested that CF mutations might
      attenuate the severity of ADPKD, whereas a third found no evidence of a
      protective effect. In this study, we investigated the impact of the commonest CF
      mutation F508del-CFTR on the formation and growth of renal cysts. As a model
      system, we used Madin-Darby canine kidney (MDCK) epithelial cells engineered to
      express wild-type and F508del human CFTR. We grew MDCK cysts in collagen gels in
      the presence of the cAMP agonist forskolin and measured transepithelial
      resistance and Cl(-) secretion with the Ussing chamber technique and assayed cell
      proliferation using nonpolarized MDCK cells. When compared with untransfected
      MDCK cells, cells expressing wild-type CFTR generated substantial numbers of
      large cysts, which grew markedly over time. By contrast, MDCK cells expressing
      F508del-CFTR formed very few tiny cysts that failed to enlarge. Interestingly,
      treatment of F508del-CFTR cysts with the CFTR corrector VRT-325 and the CFTR
      corrector-potentiator VRT-532 increased the number, but not size, of F508del-CFTR
      cysts, possibly because VRT-325 inhibited strongly cell proliferation. Based on
      its effects on transepithelial resistance, Cl(-) secretion, and cell
      proliferation, we conclude that the F508del-CFTR mutation disrupts cyst formation
      and growth by perturbing strongly fluid accumulation within the cyst lumen
      without compromising epithelial integrity.

PMID- 22874762
TI  - In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/beta
      catenin activation.
AB  - The present study investigates the differential effect of two vitamin D receptor
      agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells
      calcification in vitro. Human vascular smooth muscle cells were incubated in a
      high phosphate (HP) medium alone or supplemented with either calcitriol 10(-8)M
      (HP + CTR) or paricalcitol 3.10(-8) M (HP + PC). HP medium induced calcification,
      which was associated with the upregulation of mRNA expression of osteogenic
      factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and
      osteocalcin. In these cells, activation of Wnt/beta-catenin signaling was
      evidenced by the translocation of beta-catenin into the nucleus and the increase
      in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican.
      Addition of calcitriol to HP medium (HP + CTR) further increased calcification
      and also enhanced the expression of osteogenic factors together with a
      significant elevation of nuclear beta-catenin levels and the expression of cyclin
      D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not
      only reduced calcification but also downregulated the expression of BMP2 and
      other osteoblastic phenotype markers as well as the levels of nuclear beta
      catenin and the expression of its target genes. The role of Wnt/beta-catenin on
      phosphate- and calcitriol-induced calcification was further demonstrated by the
      inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1),
      a specific natural antagonist of the Wnt/beta-catenin signaling pathway. In
      conclusion, the differential effect of calcitriol and paricalcitol on vascular
      calcification appears to be mediated by a distinct regulation of the BMP and
      Wnt/beta-catenin signaling pathways.

PMID- 22874764
TI  - Comparison of neural targets for neuromodulation of bladder micturition reflex in
      the rat.
AB  - Spinal nerve (SN) stimulation inhibits the bladder rhythmic contraction (BRC) in
      anesthetized rats. This preparation was used to study the effects of electrical
      stimulation of the tibial nerve (TN) and the dorsal nerve of the clitoris (DNC)
      on BRC. Stimulation of the TN and DNC for 10 min produced a frequency- and
      intensity-dependent attenuation of the frequency of bladder contractions. As
      observed with the SN, 10-Hz stimulation of either TN or DNC produced the greatest
      degree of inhibition, with lower or higher frequencies being either less
      efficacious or inactive. In contrast to the prolonged inhibition produced by SN
      stimulation, both TN and DNC stimulation produced "short" lasting inhibition of
      bladder contractions and the maximal inhibition occurred during stimulation. TN
      stimulation was effective over only a narrow range of current intensities [3-4 *
      motor threshold current for inducing a toe twitch (T(mot))] and only at a
      frequency of 10 Hz. Stimulation of TN at 10 Hz, 3 * T(mot) inhibited BRC to 23%
      of control. Ten-hertz DNC stimulation at 2 * T(EAS), the threshold current for
      evoking a reflex anal sphincter contraction, decreased the frequency of
      contractions to 4% of control. Although compared with the respective threshold
      current the BRC response was more sensitive to DNC compared with TN stimulation,
      the absolute current required to reduce BRC using DNC stimulation appeared to be
      higher. Comparing the effects of TN and DNC stimulation to our previous results
      with SN stimulation, SN stimulation produces the largest duration and efficacy of
      bladder inhibition.

PMID- 22874763
TI  - Activated CD47 regulates multiple vascular and stress responses: implications for
      acute kidney injury and its management.
AB  - Ischemia-reperfusion injury (IRI) remains a significant source of early and
      delayed renal transplant failure. Therapeutic interventions have yet to resolve
      this ongoing clinical challenge although the reasons for this remain unclear. The
      cell surface receptor CD47 is widely expressed on vascular cells and in tissues.
      It has one known soluble ligand, the stress-released matricellular protein
      thrombospondin-1 (TSP1). The TSP1-CD47 ligand receptor axis controls a number of
      important cellular processes, inhibiting survival factors such as nitric oxide,
      cGMP, cAMP, and VEGF, while activating injurious pathways such as production of
      reactive oxygen species. A role of CD47 in renal IRI was recently revealed by the
      finding that the TSP1-CD47 axis is induced in renal tubular epithelial cells
      (RTEC) under hypoxia and following IRI. The absence of CD47 in knockout mice
      increases survival, mitigates RTEC damage, and prevents subsequent kidney
      failure. Conversely, therapeutic blockade of TSP1-CD47 signaling provides these
      same advantages to wild-type animals. Together, these findings suggest an
      important role for CD47 in renal IRI as a proximate promoter of injury and as a
      novel therapeutic target.

PMID- 22874765
TI  - Hyperglycemia induces Toll like receptor 4 expression and activity in mouse
      mesangial cells: relevance to diabetic nephropathy.
AB  - Diabetes is a proinflammatory state. The pattern recognition receptors, Toll-like
      receptors (TLRs), are increased in diabetic patients and have been suggested to
      play a role in diabetic nephropathy (DN). Progression of DN involves altered
      mesangial cell (MC) function with an expansion of the mesangial matrix. There is
      a paucity of data examining the role of TLR and its expression in MC. We
      hypothesize the expression of TLRs in the mesangium might be an important factor
      contributing to mesangium expansion and nephropathy. Thus we evaluated the effect
      of high glucose on TLR2 and TLR4 expression in mouse mesangial cells (MMC) in
      vitro. Exposure of MMC to 25 mM glucose for 24 h resulted in increased TLR4 mRNA
      and cell surface receptor expression compared with 5.5 mM glucose (P < 0.05).
      Interestingly, we were not able to detect expression of TLR2 in MMC. Furthermore,
      expression of a TLR4 downstream signaling cascade including myeloid
      differentiation factor 88 (MyD88), interferon regulatory factor 3 (IRF3), and
      Toll interleukin receptor domain containing adaptor inducing interferon-beta
      (TRIF)-related adaptor molecule (TRAM) were significantly increased in cells
      exposed to 25 mM glucose (P < 0.05). There was also a significant increase in NF
      kappaB activation along with increased secretion of inflammatory cytokines IL-6
      and monocyte chemotactic protein-1. Levels of transforming growth factor-beta
      were also significantly increased in the presence of 25 mM glucose (P < 0.05).
      Collectively, these data suggest that hyperglycemia activates TLR4 expression and
      activity in MC and could contribute to DN.

PMID- 22874766
TI  - Production of fermented chestnut purees by lactic acid bacteria.
AB  - The objective of this study was to develop a new chestnut-based puree, in order
      to seasonally adjust the offer and use the surplus of undersized production,
      providing, at the same time, a response to the growing demand for healthy and
      environmentally friendly products. Broken dried chestnuts have been employed to
      prepare purees to be fermented with six different strains of Lactobacillus (Lb.)
      rhamnosus and Lactobacillus casei. The fermented purees were characterized by a
      technological and sensorial point of view, while the employed strains were tested
      for their probiotic potential. Conventional in vitro tests have indicated the six
      lactobacilli strains as promising probiotic candidates; moreover, being the
      strains able to grow and to survive in chestnut puree at a population level
      higher than 8 log10 CFU/mL along 40 days of storage at 4  degrees C, the bases
      for the production of a new food, lactose-free and with reduced fat content, have
      been laid.

PMID- 22874767
TI  - Antimicrobial susceptibilities of Listeria monocytogenes strains isolated from
      food and food processing environment in Poland.
AB  - A total of 471 Listeria monocytogenes isolates from different types of food and
      food-related sources in Poland during 2004-2010 were examined. This number
      includes 200 isolates from fish, 144 from fresh and frozen vegetables, 43 ready
      to-eat products (deli foods, cold cuts), 13 from dairy products, 16 from raw
      meats, 15 from confectionery products and 40 directly from processing plants. All
      isolates were subjected to serotyping and lineage assays using PCR, and
      antimicrobial susceptibility using E-test and a broth microdilution method. Of
      all isolates, 256 (54.4%), 120 (25.5%), 59 (12.5%), 36 (7.6%) were identified as
      serotypes 1/2a (or 3a), 1/2c (or 3c), 1/2b (or 3b or 7), and 4b (or 4d or 4e),
      respectively. A direct correlation between the most common serotypes and three L.
      monocytogenes lineages was also observed. All L. monocytogenes isolates belonged
      to lineages I (20.2%) and II (79.8%). All strains were sensitive to ampicillin,
      amoxicillin, gentamicin, erythromycin, trimethoprim, rifampicin, vancomycin,
      chloramphenicol and sulfamethoxazol. Two of the L. monocytogenes strains (0.42%)
      showed phenotypic resistance. One strain was resistant to tetracycline and
      minocycline due to the presence of tet(M). It did not carry gene int, which may
      indicate that the tet(M) gene in this strain was not integrated in the transposon
      Tn916-Tn1545 family. The resistance of the second strain to ciprofloxacin and
      norfloxacin was attributed to active efflux associated with overexpression of
      gene lde. Our data indicate the low prevalence of antimicrobial resistance among
      L. monocytogenes isolates from food and food-related sources in Poland.

PMID- 22874768
TI  - Rescue screens with secreted proteins reveal compensatory potential of receptor
      tyrosine kinases in driving cancer growth.
AB  - The overall power of kinase inhibitors is substantially overshadowed by the
      acquisition of drug resistance. To address this issue, we systematically assessed
      the potential of secreted proteins to induce resistance to kinase inhibitors. To
      this end, we developed a high-throughput platform for screening a cDNA library
      encoding 3,432 secreted proteins in cellular assays. Using cancer cells
      originally dependent on either MET, FGFR2, or FGFR3, we observed a bypass of
      dependence through ligand-mediated activation of alternative receptor tyrosine
      kinases (RTK). Our findings indicate a broad and versatile potential for RTKs
      from the HER and FGFR families as well as MET to compensate for loss of each
      other. We further provide evidence that combined inhibition of simultaneously
      active RTKs can lead to an added anticancer effect.

PMID- 22874769
TI  - Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic
      mitochondria pathway.
AB  - Adjuvant use of safe compounds with anti-tumour properties has been proposed to
      improve cancer chemotherapy outcome. We aimed to investigate the effects of fish
      oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5
      fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal
      adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax+/+) and
      LS174T (Bax-/-) cells were co-treated for 24-72 h with 1 MUm-5-FU, 1 MUm-OX or 10
      MUm-IRI and/or FOE dilution corresponding to 24 MUm-EPA and 20.5 MUm-DHA.
      Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell
      viability, apoptosis and nuclear morphological changes were evaluated by
      cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'
      diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was
      used to evaluate mitochondrial dysfunction, and protein expression involved in
      mitochondrial apoptosis was determined by Western blot. In contrast to SOE, co
      treatment with FOE enhanced significantly the pro-apoptotic and cytotoxic effects
      of 5-FU, OX or IRI in HT-29 but not in LS174T cells (two-way ANOVA, P <0.01).
      These results were confirmed by the formation of apoptotic bodies in HT-29 cells.
      A significant increase in mitochondrial membrane depolarisation was observed
      after the combination of 5-FU or IRI with FOE in HT-29 but not in LS174T cells (P
      <0.05). Co-administration of FOE with the standard agents, 5-FU, OX and IRI,
      could be a good alternative to increase the efficacy of chemotherapeutic
      protocols through a Bax-dependent mitochondrial pathway.

PMID- 22874770
TI  - Exploring service users' perceptions of cognitive behavioural therapy for
      psychosis: a user led study.
AB  - BACKGROUND AND AIMS: This study explored individuals' subjective experiences of
      Cognitive Behavioural Therapy for psychosis (CBTp) with the aim of identifying
      coherent themes consistent across individual accounts and any potential barriers
      to CBTp effectiveness. METHOD: Semi-structured interviews were conducted with
      nine individuals with experience of CBTp. A qualitative Interpretive
      Phenomenological Analysis was used to analyze the data collected to identify
      common themes. RESULTS: Five super-ordinate themes emerged from our analyses: CBT
      as a process of person-centred engagement; CBT as an active process of structured
      learning; CBT helping to improve personal understanding; CBT is hard work;
      Recovery and outcomes of CBT for psychosis. CONCLUSIONS: The theoretical and
      clinical implications are discussed.

PMID- 22874771
TI  - Adjuvant interferon alfa in malignant melanoma: an interdisciplinary and
      multinational expert review.
AB  - Interferon alfa (IFNalpha) and pegylated IFNalpha2b (PegIFNalpha2b) are the only
      agents currently approved for the adjuvant treatment of resected melanoma at high
      risk of recurrence. Meta-analyses showed statistically significant disease-free
      survival (DFS) and overall survival (OS) benefits versus controls but did not
      clarify optimal dose/duration. We review data from all recent clinical trials to
      provide the latest information on dose, duration, and potential predictive
      factors of treatment success. Recent data largely confirm DFS and OS benefits but
      optimal dose/duration is not clarified. The data suggest greater responses in
      patients with stage III micro-metastatic versus macro-metastatic disease, and
      ulceration may also predict greater sensitivity to therapy, although further
      investigation is needed. Presently, IFNalpha and PegIFNalpha2b remain valid
      adjuvant therapies following resection of high-risk melanoma; the most
      appropriate treatment regimen should be determined on an individual patient basis
      according to patient lifestyle and approach, potential for toxicity, and the
      available clinical evidence.

PMID- 22874772
TI  - Caregiving burden and out-of-home mobility of cognitively impaired care
      recipients based on GPS tracking.
AB  - BACKGROUND: Out-of-home mobility refers to the realization of trips outside the
      home, by foot or by other means of transportation. Although out-of-home mobility
      is important for the well-being of older people with cognitive impairment, its
      importance for their caregivers is not clear. This study aims to clarify the
      relationship between caregiving burden and out-of-home mobility of care
      recipients using Global Positioning Systems (GPS) technology. METHODS: Seventy
      six dyads (care-recipients and caregivers) were recruited from a psychogeriatric
      center, where they underwent cognitive assessment, followed by psychosocial
      interviews at home. Care-recipients received GPS tracking kits to carry for a
      period of four weeks, whenever they left home. Mobility data and diagnostic and
      psychosocial data were examined in relation to caregiver burden. RESULTS: The
      strongest predictors of burden were care-recipients' lower cognitive status and
      more time spent walking out-of-home. An interaction was found between cognitive
      status and time spent walking in relation to caregiver burden. The relationship
      between walking and burden was stronger among caregivers of care-recipients with
      dementia than caregivers of care-recipients with no cognitive impairment or mild
      cognitive impairment. Care-recipients' behavioral and emotional states were also
      positively related to caregiver burden. CONCLUSIONS: The findings stress the
      importance of maintaining older persons' out-of-home mobility during cognitive
      decline.

PMID- 22874773
TI  - Human metapneumovirus infection among family members.
AB  - The transmission of human metapneumovirus (hMPV) among family members is not well
      understood. We identified 15 families in which multiple members were diagnosed
      with hMPV infection by real-time PCR in 2008 and 2010. Index patients ranged in
      age from 2 years to 11 years (median 5 years), and all 15 index cases were
      children who attended primary school, kindergarten, or nursery school. Contact
      patients ranged in age from 2 months to 46 years (median 6 years). Excluding five
      adult cases, contact patients were significantly younger than index patients (P =
      0.0389). Of the 12 contact children, seven (58%) were infants who were taken care
      of at home. The serial interval between the onset of symptoms in an index patient
      and the onset of symptoms in a contact patient was estimated to be 5 days. These
      results suggest that the control of school-based outbreaks is important for
      preventing hMPV infection in infants.

PMID- 22874774
TI  - NMC recognises failings.

PMID- 22874775
TI  - Diabetes dilemma: errors and alerts in insulin therapy.

PMID- 22874776
TI  - Chronic obstructive pulmonary disease: nature-nurture interactions.
AB  - A person's health status is rarely constant, it is usually subject to continual
      change as a person moves from health to illness and usually back to health again;
      the health-illness continuum illustrates this dynamism. This highlights the
      person's various states of health and illness (ranging from extremely good health
      to clinically defined mild, moderate and severe illness) and their fluctuations
      throughout the life span, until ultimately leading to the pathology associated
      with the person's death. Maintenance of a stable homeostatic environment within
      the body to support the stability of this continuum depends on a complex series
      of ultimately intracellular chemical reactions. These reactions are activated by
      environmental factors that cause the expression of genes associated with healthy
      phenotypes as well as illness susceptibility genes associated with homeostatic
      imbalances. Obviously, the body aims to support intracellular and extracellular
      environments allied with health; however, the complexity of these nature-nurture
      interactions results in illness throughout an individual's life span. This paper
      will discuss the nature-nurture interactions of chronic obstructive pulmonary
      disease.

PMID- 22874777
TI  - Cardiac rehabilitation: an effective secondary prevention intervention.
AB  - A combination of quantitative and qualitative research was used to determine the
      effectiveness of a cardiac rehabilitation (CR) programme in a cohort of patients
      referred to the service at a London hospital. Quantitative data analysis provided
      evidence of effectiveness of participation in CR in reduced hospital readmission
      rates and use of recognised pharmacological management strategies. Self-reported
      physical activity levels and quality of life (QOL) in individuals who
      participated in the cardiac rehabilitation programme were qualitatively measured
      with questionnaires. Results provided evidence of benefit in continued
      participation in exercise. However, there was no evidence of benefit to QOL
      status post participation at 1 year. A p-value of 0.001 provided significant
      statistical evidence supporting the hypothesis of benefit in continued
      participation in exercise in participants following attendance at a cardiac
      rehabilitation programme. QOL status; a statistically significant p-value of
      0.001 rejected the hypothesis (H1) of benefit. This would imply that
      participation CR programmes does not appear to provide sustained benefits in QOL.
      A number of moderating variables were suggested as explaining the finding such as
      homogeneity of respondents, age, mood bias and the timeframe of 1 year between
      participation in rehabilitation and self-reporting. CR appears to be an effective
      but time-limited intervention in relation to improvements in QOL. Collaborative
      working partnerships between specialist interventions, such as CR with chronic
      disease management strategies may provide greater sustainability of benefits
      gained from participation in cardiac rehabilitation programmes.

PMID- 22874778
TI  - Patient stoma care:  educational theory in practice.
AB  - Patients undergoing stoma formation encounter many challenges including
      psychosocial issues, relationship concerns and fear of leakage. Leakage,
      inappropriate product usage and poor patient adaptation post stoma formation has
      cost implications for the NHS. Developing good, practical stoma care skills has
      been identified as improving patient outcomes, promoting the provision of quality
      care and improving efficiency within the NHS. However, a thorough literature
      search indicated that there is little research available on patient stoma care
      education. This is considered surprising by Metcalf (1999), O'Connor (2005) and
      the author of this article. This article considers and adapts generic educational
      theory to make it pertinent to patient stoma care education in order to bridge
      the gap between theory and practice.

PMID- 22874780
TI  - Nurse-led ward rounds: a valuable contribution to acute stroke care.
AB  - Stroke is a devastating condition. The Royal College of Physicians (2008)
      highlights that integrated stroke care can improve patient care. Nurses are an
      integral part of the multidisciplinary team, providing 24/7 stroke care from
      planning and implementing care to the evaluation of the patient's condition. To
      improve the way nurses manage stroke patients in an acute setting, a nurse-led
      ward round was initiated to look at essential nursing care. The Imperial College
      Healthcare Trust stroke senior nursing team, consisting of a clinical nurse
      specialist, a ward manager, and a charge nurse, have organised a weekly stroke
      nurse-led ward round. The team takes rounds to each stroke patient in the ward to
      examine and evaluate the essentials of nursing care (e.g. oral care, skin
      integrity, continence, bowel and bladder management), and current stroke outcome
      measures. During the rounds, the team address nursing issues, make appropriate
      nursing goals, and discuss their plans with the nurses and other members of the
      team. A nurse-led ward round has addressed nursing issues in a timely proactive
      fashion. The initiative has been successful in improving clinical communication
      between nurses and patient involvement in their care planning. It has also
      empowered nurses to make decisions within their professional arena, and its
      contribution has had an impact on patient care and safety through early detection
      and prevention of stroke complications.

PMID- 22874779
TI  - Knowledge of immunosuppressive drugs used in kidney transplants.
AB  - AIM: A key role of renal nurses is the correct and safe administration of
      immunosuppressive drug therapy (ImmRx) to kidney transplant recipients. The
      authors sought to examine the knowledge and competency of ImmRx in kidney
      transplant patients and whether an annual kidney transplant nurse education
      programme had any beneficial effects. METHODS: The study population was comprised
      of 63.2% (n=50/79) of all nurses from renal wards (ward A (n=17/35), ward B
      (n=21/32)) and 12 nurses from a high-dependency urology ward (ward C (n=12)).
      Kidney transplant patients usually receive inpatient care in wards A, B or C only
      as these wards specialise in urology and renal care. Each nurse completed a 35
      question test that covered ImmRx in areas of indication, identification,
      interaction, pharmcokinetics/pharmacodynamics, therapeutic drug monitoring,
      administration and adverse effects. A minimum score of 70% was required to pass
      the test. RESULTS: Only 46% of participants passed the test. The proportion of
      nurses who passed was not significantly different with respect to years of
      nursing experience, professional rank, postgraduate nursing qualifications or
      ward location. Unexpectedly, a greater proportion of nurses who did not attend
      the education programme passed the test (63.6%; n=14/22) than those who did
      attend it (32.1%; n=9/28]; p=0.03). Notably, 24% (n=12/50), 4% (n=2/50) and 4%
      (n=2/50) were unable to correctly answer any of the identification, interaction
      and therapeutic drug monitoring questions. CONCLUSION: These findings suggest
      that the nurses' understanding and knowledge of ImmRx is insufficient and they
      need to update their knowledge on ImmRx continually.

PMID- 22874781
TI  - Over-the-counter medicines:  their place in self-care.
AB  - Over the last 20 years, there has been a shift in Western countries' healthcare
      policy to empower patients to exercise self-care by taking greater control in
      managing their own health, especially in cases where their conditions are deemed
      minor and self-limiting. In the UK, this has been facilitated by the Department
      of Health in making more medicines available to the public without the need for a
      prescription. This article highlights how policy is affecting practice, what
      attitudes the public and health professionals have toward greater medicine
      availability, and considers their place in patient management.

PMID- 22874783
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 3: learning
      from experience.

PMID- 22874782
TI  - Sexually transmitted infections in men who have sex with men.
AB  - For the first time in 10 years, there has been a fall in the number of diagnoses
      of sexually transmitted infections (STIs) in England; new diagnoses fell by 1%.
      Infection rates continue to grow among gay men and other men who have sex with
      men. Men who have sex with men are at more risk of developing an STI than other
      men in the population. This article considers the overall trends and diagnoses of
      STIs in England. A focus in particular on men who have sex with men is provided
      with an emphasis on lymphogranuloma venereum. Data is presented in order to
      provide the nurse with an overview of trends and the burden of STIs on this group
      of people; STIs are still on the increase in men who have sex with men. This
      article makes recommendations for action and emphasises the important role of the
      nurse in making men who have sex with men a priority for targeted HIV and STI
      prevention and health promotion work.

PMID- 22874784
TI  - Student mentoring:  supporting first years.

PMID- 22874785
TI  - Performance, risk and patient safety in health and social care.

PMID- 22874786
TI  - The RCN commission on  education: what does it mean?

PMID- 22874787
TI  - Finding your voice as a student nurse.

PMID- 22874788
TI  - Compassionate leadership.

PMID- 22874789
TI  - Why are UK nurses so well respected in other countries?

PMID- 22874790
TI  - Effect of acute and fractionated irradiation on hippocampal neurogenesis.
AB  - Ionizing radiation has become an inevitable health concern emanating from natural
      sources like space travel and from artificial sources like medical therapies. In
      general, exposure to ionizing radiation such as gamma-rays is one of the methods
      currently used to stress specific model systems. In this study, we elucidated the
      long-term effect of acute and fractionated irradiation on DCX-positive cells in
      hippocampal neurogenesis. Groups of two-month-old C57BL/6 female mice were
      exposed to whole-body irradiation at acute dose (5 Gy) or fractional doses (1 Gy
      * 5 times and 0.5 Gy * 10 times). Six months after exposure to gamma-irradiation,
      the hippocampus was analyzed. Doublecortin (DCX) immunohistochemistry was used to
      measure changes of neurogenesis in the subgranular zone (SGZ) of the hippocampal
      dentate gyrus (DG). The number of DCX-positive cells was significantly decreased
      in all acute and fractionally irradiation groups. The long-term changes in DCX
      positive cells triggered by radiation exposure showed a very different pattern to
      the short-term changes which tended to return to the control level in previous
      studies. Furthermore, the number of DCX-positive cells was relatively lower in
      the acute irradiation group than the fractional irradiation groups (approximately
      3.6-fold), suggesting the biological change on hippocampal neurogenesis was more
      susceptible to being damaged by acute than fractional irradiation. These results
      suggest that the exposure to  gamma-irradiation as a long-term effect can trigger
      biological responses resulting in the inhibition of hippocampal neurogenesis.

PMID- 22874791
TI  - Demethylzeylasteral exhibits strong inhibition towards UDP
      glucuronosyltransferase (UGT) 1A6 and 2B7.
AB  - Inhibition of UDP-glucuronosyltransferase (UGT) isoforms can result in severe
      clinical results, including clinical drug-drug interactions (DDI) and metabolic
      disorders of endogenous substances. The present study aims to investigate the
      inhibition of demethylzeylasteral (an important active component isolated from
      Tripterygium wilfordii Hook F.) towards three important UGT isoforms UGT1A6,
      UGT1A9 and UGT2B7. The results showed that 100 MUM of demethylzeylasteral
      exhibited strong inhibition towards UGT1A6 and UGT2B7, with negligible influence
      towards UGT1A9. Furthermore, Dixon and Lineweaver-Burk plots showed the
      inhibition of UGT1A6 and UGT2B7 by demethylzeylasteral was best fit to
      competitive inhibition, and the inhibition kinetic parameters (Ki) were
      calculated to be 0.6 MUM and 17.3 MUM for UGT1A6 and UGT2B7, respectively. This
      kind of inhibitory effect need much attention when demethylzeylasteral and
      demethylzeyasteral-containing herbs (e.g., Tripterygium wilfordii Hook F.) were
      co-administered with the drugs mainly undergoing UGT1A6, UGT2B7-catalyzed
      metabolism. However, when extrapolating the in vivo clinical results using our
      present in vitro data, many complex factors might affect final results, including
      the contribution of UGT1A6 and UGT2B7 to the metabolism of compounds, and the
      herbal or patients' factors affecting the in vivo concentration of
      demethylzeylasteral.

PMID- 22874792
TI  - Preservation of Bacillus firmus strain 37 and optimization of cyclodextrin
      biosynthesis by cells immobilized on loofa sponge.
AB  - The preservation of Bacillus firmus strain 37 cells by lyophilization was
      evaluated and response surface methodology (RSM) was used to optimize the beta
      cyclodextrin (beta-CD) production by cells immobilized on loofa sponge.
      Interactions were studied with the variables temperature, pH and dextrin
      concentration using a central composite design (CCD). Immobilization time
      influence on beta-CD production was also investigated. B. firmus strain 37 cells
      remained viable after one year of storage, showing that the lyophilization is a
      suitable method for preservation of the microorganism. From the three-dimensional
      diagrams and contour plots, the best conditions for beta-CD production were
      determined: temperature 60  degrees C, pH 8, and 18% dextrin. Considering that
      the amount of dextrin was high, a new assay was carried out, in which dextrin
      concentrations of 10, 15, and 18% were tested and the temperature of 60  degrees
      C and pH 8 were maintained. The results achieved showed very small differences
      and therefore, for economic reasons, the use of 10% dextrin is suggested.
      Increasing the immobilization time of cells immobilized on synthetic sponge the
      beta-CD production decreased and did not change for cells immobilized on loofa
      sponge. The results of this research are important for microorganism preservation
      and essential in the optimization of the biosynthesis of CD.

PMID- 22874793
TI  - Computerized modeling of adenosine triphosphate, adenosine triarsenate and
      adenosine trivanadate.
AB  - Computerized molecular models of adenosine triphosphate, adenosine tri-arsenate
      and adenosine trivanadate have been generated using the molecular mechanics
      technique. The analysis of structural parameters indicated that, at least
      theoretically, adenosine triarsenate is a realistic candidate for replacement of
      adenosine triphosphate in biochemical pathways. On the contrary, the structural
      arrangement of the inorganic segment of adenosine trivanadate does not seem to be
      capable of withstanding a swift hydrolytical splitting in aqueous milieu. It was
      shown that the universal force field as implemented in Gaussian software packages
      is an appropriate tool for the optimization of less-common bioactive
      compositions.

PMID- 22874794
TI  - Fabrication and characteristics of ZnO/OAD-InN/PbPc hybrid solar cells prepared
      by oblique-angle deposition.
AB  - In this work, lead phthalocyanine (PbPc) and ZnO/InN inorganic semiconductor
      films prepared by oblique-angle deposition (OAD) were layered to form
      heterojunction organic/inorganic hybrid photovoltaic solar cells. Among the
      available organic materials, phthalocyanines, particularly the non-planar ones
      such as PbPc, are notable for their absorption in the visible and near infrared
      regions. The organic/inorganic hybrid solar cells fabricated on ZnO/OAD-InN/PbPc
      showed short-circuit current density (J(SC)), open-circuit voltage (V(OC)), and
      power conversion efficiencies (eta) of 1.2 mA/cm2, 0.6 V and 0.144%,
      respectively.

PMID- 22874795
TI  - Patients' evaluation of hospital foodservice quality in Italy: what do patients
      really value?
AB  - OBJECTIVE: Patients often do not eat/drink enough during hospitalization. To
      enable patients to meet their energy and nutritional requirements, food and
      catering service quality and staff support are therefore important. We assessed
      patients' satisfaction with hospital food and investigated aspects influencing
      it. DESIGN: We conducted a cross-sectional study collecting patients' preferences
      using a slightly modified version of the Acute Care Hospital Foodservice Patient
      Satisfaction Questionnaire (ACHFPSQ). Factor analysis was carried out to reduce
      the number of food-quality and staff-issue variables. Univariate and multivariate
      ordinal categorical regression models were used to assess the association between
      food quality, staff issues, patients' characteristics, hospital recovery aspects
      and overall foodservice satisfaction (OS). SETTING: A university hospital in
      Florence, Italy, in the period November-December 2009. SUBJECTS: Hospital
      patients aged 18+ years (n 927). RESULTS: Of the 1288 questionnaires distributed,
      927 were returned completely or partially filled in by patients and 603 were
      considered eligible for analysis. Four factors (explained variance 64.3 %,
      Cronbach's alpha alpha(C) = 0.856), i.e. food quality (FQ; alpha(C) = 0.74), meal
      service quality (MSQ; alpha(C) = 0.73), hunger and quantity (HQ; alpha(C) = 0.74)
      and staff/service issues (SI; alpha(C) = 0.65), were extracted from seventeen
      items. Items investigating staff/service issues were the most positively rated
      while certain items investigating food quality were the least positively rated.
      After ordinal multiple regression analysis, OS was only significantly associated
      with the four factors: FQ, MSQ, HQ and SI (OR = 17.2, 6.16, 3.09 and 1.75,
      respectively, P < 0.001), and gender (OR = 1.53, P = 0.024). CONCLUSIONS: The
      most positively scored aspects of foodservice concerned staff/service, whereas
      food quality was considered less positive. The aspects that most influenced
      patients' satisfaction were those related to food quality.

PMID- 22874796
TI  - The implications of acute rejection and reduced allograft function on health care
      expenditures in contemporary US kidney transplantation.
AB  - BACKGROUND: The economic ramifications of acute rejection (AR) are not well
      characterized in a contemporary population of kidney transplant recipients.
      METHODS: Data for Medicare-insured transplant recipients in 2000 to 2007
      (n=45,250) were drawn from the United States Renal Data System. AR events were
      ascertained from the Organ Procurement and Transplantation Network reports
      covering months 0 to 12 (yr1), 13 to 24 (yr2), and 25 to 36 (yr3) after
      transplantation. AR was subclassified as antibody (Ab)-treated AR or other
      management (non-Ab-treated AR). The marginal cost impact of AR events during and
      before a period of interest was quantified by multivariate linear regression
      including covariates for recipient, donor, and transplant factors. RESULTS: Among
      recipients of standard criteria donor allografts, both Ab-treated AR events (yr1,
      $22,407; yr 2, $18,803; yr3, $13,909) and non-Ab-treated AR events (yr1, $14,122;
      yr2, $7852; yr3, $8234) were associated with significant increases in the cost of
      care. Patterns were similar among recipients of living donor and expanded
      criteria donor transplants. After weighting by population frequency, AR accounted
      for 2.3% to 3.8% of total costs incurred during 1 year of posttransplantation
      care. Subanalysis of recipients with yr1 estimated glomerular filtration rate
      (eGFR) information demonstrated markedly stronger cost variation across eGFR
      levels. For example, among those with non-Ab-treated AR, adjusted total yr2 costs
      were $22,747 with eGFR of 60 mL/min/1.73 m or higher but $43,881 with eGFR of 30
      mL/min/1.73 m or lower. CONCLUSIONS: AR is a significant contributor to
      individual posttransplantation costs. However, because of its low frequency, AR
      accounts for a small proportion of posttransplantation costs in the population.
      Healthcare costs in patients with AR are markedly higher among those with reduced
      compared with preserved allograft function.

PMID- 22874797
TI  - Proteomics in hypertension.
AB  - Proteomics, the study of the proteins making up the proteome, has emerged in
      recent years as an important tool in several different fields of medical research
      for early disease detection, for assessment of response to treatment and for
      unravelling underlying pathophysiological mechanisms. Although the majority of
      patients with hypertension are treated in a similar manner, the causes underlying
      the condition are diverse, and often poorly understood. Genetic studies have
      implicated several different candidate genes, but it may be that examination of
      the 'downstream' products of genes, the proteins, will help to improve
      understanding of the link between the environmental and genetic effects that
      contribute towards development of hypertension. Proteomic studies can be
      performed quickly and reliably on several different sample types including plasma
      and urine, requiring minimal pre-test preparation. In this review, we will
      compare the different analytical platforms and technical issues involved in
      proteomic analysis. We will discuss existing studies of proteomics in
      hypertension, as well as related conditions such as renal disease, pre-eclampsia
      and coronary artery disease. We will also explore potential future applications
      of proteomics-based research, which may ultimately lead to improved population
      screening, monitoring of therapy and early detection of target organ damage.

PMID- 22874804
TI  - Analysis of glutathione S-transferase genes polymorphisms and the risk of
      schizophrenia in a sample of Iranian population.
AB  - Glutathione S-transferases (GSTs) are major intracellular antioxidants, which,
      impaired in their function, are involved in the progress of schizophrenia (SCZ).
      The aim of this case-control study was to investigate the association between the
      polymorphism of glutathione S-transferases M1 (GSTM1), T1 (GSTT1), the
      glutathione S-transferase P1 gene (GSTP1) and SCZ. We isolated genomic DNA from
      peripheral blood of 93 individuals with SCZ and 99 healthy control subjects'
      genotypes analyzing them for GSTM1, GSTT1 and GSTP1 using polymerase chain
      reaction. The analysis of the gene-gene interaction between GSTs indicated that
      the magnitude of the association was greater for the combined AG/GSTT1 & GSTM1
      genotypes (OR = 2.51; 95% CI: 1.13-5.63, P = 0.02). The AG and combined AG + GG
      genotypes of GSTP1 increased the risk of SCZ (OR = 1.83; 95% CI: 0.94-3.75 and OR
      = 1.71; 95% CI: 0.92-3.19, respectively). The genotypes of GSTT/NULL, NULL/GSTM
      and NULL/NULL increased the risk of SCZ (OR = 2.05; 95% CI: 0.9-4.74; OR = 2.0;
      95% CI: 1.68-2.31; and OR = 1.8; 95% CI: 0.57-2.46, respectively). The present
      study supports previous data that suggest that impairment in the function of GSTs
      genes may increase the risk of SCZ.

PMID- 22874798
TI  - Mechanosensitive Ca(2+) permeant cation channels in human prostate tumor cells.
AB  - The acquisition of cell motility plays a critical role in the spread of prostate
      cancer (PC), therefore, identifying a sensitive step that regulates PC cell
      migration should provide a promising target to block PC metastasis. Here, we
      report that a mechanosensitive Ca(2+)-permeable cation channel (MscCa) is
      expressed in the highly migratory/invasive human PC cell line, PC-3 and that
      inhibition of MscCa by Gd(3+) or GsMTx-4 blocks PC-3 cell migration and
      associated elevations in [Ca(2+)](i). Genetic suppression or overexpression of
      specific members of the canonical transient receptor potential Ca(2+) channel
      family (TRPC1 and TRPC3) also inhibit PC-3 cell migration, but they do so by
      mechanisms other that altering MscCa activity. Although LNCaP cells are
      nonmigratory, they also express relatively large MscCa currents, indicating that
      MscCa expression alone cannot confer motility on PC cells. MscCa in both cell
      lines show similar conductance and ion selectivity and both are functionally
      coupled via Ca(2+) influx to a small Ca(2+)-activated K(+) channel. However,
      MscCa in PC-3 and LNCaP cell patches show markedly different gating dynamics-
      while PC-3 cells typically express a sustained, non-inactivating MscCa current,
      LNCaP cells express a mechanically-fragile, rapidly inactivating MscCa current.
      Moreover, mechanical forces applied to the patch, can induce an irreversible
      transition from the transient to the sustained MscCa gating mode. Given that
      cancer cells experience increasing compressive and shear forces within a growing
      tumor, a similar shift in channel gating in situ would have significant effects
      on Ca(2+) signaling that may play a role in tumor progression.

PMID- 22874805
TI  - The power of poop: probiotics and fecal microbial transplant.

PMID- 22874806
TI  - Mycobacterium avium Subspecies paratuberculosis in Crohn's disease: the puzzle
      continues.

PMID- 22874808
TI  - Duloxetine-induced lymphocytic colitis.

PMID- 22874807
TI  - The association of primary hyperparathyroidism with pancreatitis.
AB  - The association between primary hyperparathyroidism (PHPT) and acute or chronic
      pancreatitis is controversial. For this reason, we conducted a review of the
      literature over the past 30 years to explore the relationship between these 2
      disorders. Ten retrospective studies each with >50 patients diagnosed with PHPT
      were identified. With the notable exception of 2 studies, the rate of
      pancreatitis among patients with PHPT was higher than that reported in general
      among hospitalized patients without PHPT. A higher serum calcium level may
      contribute to pancreatitis in these cases, along with additional genetic or
      environmental insults. Hypercalcemia may predispose the pancreatic acinar cell to
      abnormal, sustained calcium levels, lead to premature pancreatic protease
      activation, and pancreatitis. Although there was only short-term follow-up, most
      reports cited that definitive treatment of PHPT by parathyroidectomy led to the
      resolution of pancreatitis attacks. The published cohorts of patients with PHPT
      and pancreatitis are subject to bias, because serum calcium screening was not
      universally performed among all control nonpancreatitis patients to evaluate for
      PHPT. However, the pooled clinical and experimental data suggest an association
      between PHPT and pancreatitis and implicate hypercalcemia. For clinicians, it is
      important to recognize pancreatitis in patients with PHPT and, conversely, to
      consider PHPT by checking serum calcium levels in patients, who present with an
      unexplained pancreatitis.

PMID- 22874809
TI  - WGO training center updates. WGO is pleased to bring you periodic updates on the
      14 training centers & the wonderful work they are accomplishing.

PMID- 22874819
TI  - Pitfall Intention Explanation Task with Clue Questions (Pitfall task): assessment
      of comprehending other people's behavioral intentions in Alzheimer's disease.
AB  - BACKGROUND: In Alzheimer's disease (AD) patients, deficits in contextual
      understanding and intentions/beliefs of other people (theory of mind; ToM) cause
      communication problems between patients and caregivers. To evaluate deficits of
      contextual understanding/ToM, we developed the Pitfall Intention Explanation Task
      with Clue Questions (Pitfall task). METHODS: We recruited 26 healthy older adults
      in clinical dementia rating (CDR) 0, and 62 outpatients: 12 with amnestic mild
      cognitive impairment (aMCI) in CDR 0.5; 36 mild AD in CDR 1; and 14 moderate AD
      in CDR 2. The Pitfall task consists of a single-frame cartoon that shows a
      character's intention and seven serial questions that provide clues for
      contextual understanding/ToM. RESULTS: The total score (0-7) was decreased with
      progression of AD (CDR 0, 5.4 +/- 2.6; CDR 0.5, 3.7 +/- 2.7; CDR 1, 1.9 +/- 3.1;
      CDR 2, 0.0 +/- 0.0; respectively). In CDR 0, two-third of the participants
      responded correctly without clue questions. In CDR 0.5, one-third of the
      participants responded correctly without clue questions, and half of them
      understood with the help of the clue questions. In CDR 1, one-fourth of the
      participants responded correctly without clue questions, and the clue questions
      did not increase the correct response. In CDR 2, none responded correctly.
      Additionally, the Pitfall task provided the chance for patients' families to
      observe patients' responses. CONCLUSION: Contextual understanding/ToM, a kind of
      social cognition, was impaired with progression of AD. The Pitfall task evaluates
      the function quickly with low burden for memory function, and may provide helpful
      clues for caregivers to achieve good communication with AD patients.

PMID- 22874820
TI  - Epigenetics in asthma and COPD.
AB  - Epigenetic mechanisms are likely to play a role in many complex diseases, the
      extent of which we only beginning to understand. COPD and asthma are two
      respiratory diseases subject to strong environmental influences depending on
      underlying genetic susceptibility. Epigenetic mechanisms such as DNA methylation,
      histone modification and microRNA may be involved in these processes by
      modulating environmental effects to influence disease development. Given their
      demonstrated modifiable nature, epigenetic mechanisms may open new possibilities
      for therapeutic intervention. Here we give an overview of recent developments in
      the field of respiratory epigenetics in relation to asthma and COPD in the
      context of our current understanding of mechanisms leading to such diseases.

PMID- 22874821
TI  - Nrf2-keap1 system versus NF-kappaB: the good and the evil in chronic kidney
      disease?
AB  - Inflammation and oxidative stress are two major components involved in the
      atherogenic process generated by the innate immune response to lipoprotein
      peroxidation, which is accelerated in patients with chronic kidney disease (CKD).
      Whereas the redox-sensitive transcription factor nuclear factor-kappaB (NF
      kappaB) plays an important role in the coordinated expression of inflammatory
      genes, the nuclear factor E2-related factor 2 (Nrf2) is the transcription factor
      that is responsible for both constitutive and inducible expression of antioxidant
      response element (ARE)-regulated genes. Thus, Nrf2 can regulate antioxidant and
      anti-inflammatory cellular responses of this system, playing an important
      protective role on the development of the uremic phenotype. This review describes
      the Nrf2 system and its possible role in CKD patients.

PMID- 22874822
TI  - Left ventricular dysfunction is associated with cerebral grey matter injury: an
      in-vivo brain MRI segmentation study.
AB  - BACKGROUND AND PURPOSE: Patients with heart failure often experience cognitive
      deficits. The relationship between systolic function and cerebral gray matter
      injury is unclear. METHODS: An automated program SIENAX (v2.2) was used to
      extract brain volume and for segmentation of grey and white matter in subjects
      with low left ventricular ejection fraction (< 50%) and normal ejection fraction
      (>= 50%). T1-weighted spin-echo axial sequences were used for analysis. RESULTS:
      14 cases with low left ventricular ejection fraction and 14 age-matched controls
      were evaluated. A modest correlation between grey matter volume and low left
      ventricular ejection fraction was demonstrated (r=0.51, p=0.06), not seen with
      white matter volumes. The mean grey matter volume was 507.4+/-166.3 ml in the low
      left ventricular ejection fraction group and 541.3+/-167.2 ml in the control
      group (p=0.57). CONCLUSION: Low left ventricular ejection fraction may lead to
      cerebral grey matter injury. Larger studies including multi-modal MRI and
      neuropsychological assessments are warranted to explore potential mechanisms.

PMID- 22874823
TI  - The effect of relatedness on the response of Adalia bipunctata L. to oviposition
      deterring cues.
AB  - Larvae of aphidophagous ladybirds leave a cue in their tracks that deters
      oviposition. The influence of relatedness on this behaviour is for the first time
      explored in this paper. Two-spot ladybird females (Adalia bipunctata L.) under
      different conditions (young and naive, young and experienced, and old and naive)
      were exposed either to (i) clean filter paper, (ii) filter paper contaminated
      with unrelated larval tracks or (iii) filter paper contaminated with related
      larval tracks from their offspring. Oviposition time was recorded during nine
      hours. Oviposition was inhibited by larval tracks, and was more so by related
      than unrelated ones. Experienced females showed the same behaviour but with lower
      intensity. With old females, response was not significant with any type of larval
      tracks. This is the first report of the effect of relatedness on a ladybird's
      response to larval tracks.

PMID- 22874824
TI  - The hierarchy of evidence:  is wound care generalisable?

PMID- 22874825
TI  - A review of medical-grade  honey in wound care.
AB  - In the current healthcare environment, clinicians are increasingly under pressure
      to use wound care products that are cost effective. This includes products that
      can be used in a variety of wounds to achieve different outcomes, depending on
      the wound-bed requirements. Medical-grade honey has emerged as a product that can
      achieve a variety of outcomes within the wound and is safe and easy to use. This
      article reviews the use of a medical-grade honey, with a view to including it on
      the wound care formulary in both primary and secondary care. It featured in a
      poster presentation at the Wounds UK conference at Harrogate in 2011.

PMID- 22874826
TI  - A curriculum to ensure  nursing staff competency.
AB  - Nurses and healthcare assistants (HCAs) involved in tissue viability are expected
      to be competent, but there is little agreement over how to define competence or
      the expertise required by people filling different roles. Most training in
      England is provided in house by tissue viability nurses or interested non
      specialists; England is lagging behind Scotland and Wales in terms of learning
      materials and other resources. Staff members at a strategic health authority were
      surveyed so a consensus could be reached over a basic curriculum for tissue
      viability and the competence expected of nurses and HCAs at different levels of
      seniority. Respondents agreed that five topics should be covered by both nurses
      and HCAs: wound healing; leg ulceration; pressure ulceration; diabetic foot; and
      skin care. Levels of expertise and competence would depend on seniority. The
      curriculum provides a checklist that local tissue viability nurses can use as a
      basis for training colleagues. Trusts and educational providers should set a
      curriculum for tissue viability and standards of competence.

PMID- 22874827
TI  - Hard-to-heal venous-lymphatic  leg ulcers: a special case.
AB  - In the treatment of this 56-year-old male, the aim was to attend to his multiple
      pathologies, reducing his venous-lymphatic oedema on both legs, closing the
      extended ulcers and improving his quality of life. The patient received treatment
      in a community-based wound healing clinic. After various local therapies were not
      successful, the wounds were cleansed with saline and covered with a biocellulose
      dressing (BWD) and polyhexanide (PHMB), after which a short-stretch bandage
      system was applied. Compression was then switched to a tubular compression
      system. At day 0, both lower legs had significant oedema and circumferential
      venous-lymphatic ulcers, and the left leg showed signs of inflammation. However,
      at day 8, inflammation, oedema and ulcer area had reduced. After 2 months, the
      ulcers were almost closed and the oedema had reduced to a level where the tubular
      compression system could be applied. Treatment using BWD and compression and good
      adherence to this regimen led to ulcer closure. This improved the patients'
      quality of life significantly.

PMID- 22874828
TI  - NPWT and moist wound dressings in the treatment of the diabetic foot.
AB  - OBJECTIVES: To compare the use of negative pressure wound therapy (NPWT) and
      conventional wound dressings in the treatment of diabetic foot wounds. This
      article reviews research that compares the two treatments on partial foot
      amputations, foot ulcers, infected wounds and dehisced post-surgical wounds.
      METHODS: A systematic literature search was carried out using CINAHL, MEDLINE and
      the Cochrane Library to locate and critique key studies comparing NPWT and
      conventional wound dressings to determine their quality. FINDINGS: NPWT was found
      to be more effective in treating diabetic foot wounds compared with conventional
      wound dressings. NPWT was quicker at forming granulation tissue, achieving wound
      closure, removing infection from foot ulcer beds and decreasing wound dimensions.
      Data also showed greater incidence of amputations in those patients treated with
      moist wound dressings. IMPLICATIONS: Findings suggest that NPWT could be used as
      a primary treatment for diabetic foot wounds. Factors such as cost effectiveness
      and patient acceptability may have an impact on this treatment and will need to
      be investigated in implementing NPWT into practice.

PMID- 22874829
TI  - Effectiveness of association splitting in reducing unwanted intrusive thoughts in
      a nonclinical sample.
AB  - BACKGROUND: Association Splitting (AS) is a novel cognitive technique, which has
      shown some promise for the reduction of obsessive thoughts in patients with
      obsessive-compulsive disorder (OCD). Its effect on unwanted intrusive thoughts
      (UITs) in the general population is yet unknown. METHOD: Our experimental study
      tested the effect of AS in 49 participants who reported UITs as a regular
      problem. Participants were randomly allocated either to an AS versus waitlist
      control (WL) condition. The White Bear Suppression Inventory (WBSI) was used for
      measuring changes over time. RESULTS: Significant group differences were found
      across time. Relative to WL, AS exerted a positive effect on the reduction of
      UITs yielding a large effect size. According to self-report AS exerted a positive
      effect 6 days after the participants had initiated the exercises. All subjects in
      the AS condition judged the technique as effective. CONCLUSION: Results suggest
      that AS could be a suitable intervention to help people with a potential
      vulnerability to a clinical problem to control their UITs.

PMID- 22874830
TI  - Pine terpenoid defences in the mountain pine beetle epidemic and in other conifer
      pest interactions: specialized enemies are eating holes into a diverse, dynamic
      and durable defence system.

PMID- 22874831
TI  - Interactive effects of water supply and defoliation on photosynthesis, plant
      water status and growth of Eucalyptus globulus Labill.
AB  - Increased climatic variability, including extended periods of drought stress, may
      compromise on the health of forest ecosystems. The effects of defoliating pests
      on plantations may also impact on forest productivity. Interactions between
      climate signals and pest activity are poorly understood. In this study, we
      examined the combined effects of reduced water availability and defoliation on
      maximum photosynthetic rate (A(sat)), stomatal conductance (g(s)), plant water
      status and growth of Eucalyptus globulus Labill. Field-grown plants were
      subjected to two water-availability regimes, rain-fed (W-) and irrigated (W+). In
      the summer of the second year of growth, leaves from 75% of crown length removed
      from trees in both watering treatments and physiological responses within the
      canopies were examined. We hypothesized that defoliation would result in improved
      plant water status providing a mechanistic insight into leaf- and canopy-scale
      gas-exchange responses. Defoliated trees in the W+ treatment exhibited higher
      A(sat) and g(s) compared with non-defoliated trees, but these responses were not
      observed in the W- treatment. In contrast, at the whole-plant scale, maximum
      rates of transpiration (E(max)) and canopy conductance (G(Cmax)) and soil-to-leaf
      hydraulic conductance (K(P)) increased in both treatments following defoliation.
      As a result, plant water status was unaffected by defoliation and trees in the
      defoliated treatments exhibited homeostasis in this respect. Whole-plant soil-to
      leaf hydraulic conductance was strongly correlated with leaf scale g(s) and
      A(sat) following the defoliation, providing a mechanistic insight into
      compensatory up-regulation of photosynthesis. Above-ground height and diameter
      growth were unaffected by defoliation in both water availability treatments,
      suggesting that plants use a range of responses to compensate for the impacts of
      defoliation.

PMID- 22874832
TI  - Development and growth of primordial shoots in Norway spruce buds before visible
      bud burst in relation to time and temperature in the field.
AB  - The timing of bud development in ecodormancy is critical for trees in boreal and
      temperate regions with seasonally alternating climates. The development of
      vegetative buds and the growth of primordial shoots (the primordial shoot ratio)
      in Norway spruce were followed by the naked eye and at stereo and light
      microscopic levels in fresh-cut and fixed buds obtained by regular field
      samplings during the spring of 2007, 2008 and 2009. Buds were collected from 15
      randomly selected trees (all 16 years old in 2007) of one southern Finnish half
      sib family. The air temperature was recorded hourly throughout the observation
      period. In 2008 and 2009, initial events in the buds, seen as accumulation of
      lipid droplets in the cortex area, started in mid-March and were depleted in late
      April, simultaneously with the early development of vascular tissue and
      primordial needles. In mid-April 2007, however, the development of the buds was
      at least 10 days ahead as a result of warm spells in March and early April.
      Variation in the timing of different developmental phases within and among the
      sample trees was negligible. There was no clear one-to-one correspondence between
      the externally visible and the internal development of the buds. The dependence
      of the primordial shoot ratio on different types of temperature sum was studied
      by means of regression analysis. High coefficients of determination (R(2) ~ 95%)
      were attained with several combinations of the starting time (beginning of the
      year/vernal equinox), the threshold value (from -3 to +5  degrees C), and the
      time step (hour/day) used in the temperature summation, i.e., the prediction
      power of the primordial shoot ratio models turned out to be high, but the
      parameter estimate values were not unambiguous. According to our results,
      temperature sums describe the growth of the primordial shoot inside the bud
      before bud burst. Thus, the results provide a realistic interpretation for the
      present phenological models of bud development that are based on temperature sums
      and external observations of bud burst only, and they also provide new tools for
      improving the models.

PMID- 22874833
TI  - Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin
      binding protein-dependent reduction of beta-catenin.
AB  - Sucrose nonfermenting 1 (Snf1)-related kinase (SNRK) is a serine/threonine kinase
      with sequence similarity to AMP-activated protein kinase (AMPK); however, its
      function is not well characterized. We conducted a gene array to determine which
      genes are regulated by SNRK. The array demonstrated that SNRK overexpression
      increased the levels of genes involved in cell proliferation, including calcyclin
      binding protein (CacyBP), a member of the ubiquitin ligase complex that targets
      nonphosphorylated beta-catenin for degradation. We confirmed that SNRK increased
      CacyBP mRNA and protein, and decreased beta-catenin protein in HCT116 and RKO
      colon cancer cells. Furthermore, SNRK inhibited colon cancer cell proliferation,
      and CacyBP down-regulation reversed the SNRK-mediated decrease in proliferation
      and beta-catenin. SNRK overexpression also decreased beta-catenin nuclear
      localization and target gene transcription, and beta-catenin down-regulation
      reversed the effects of SNRK knockdown on proliferation. SNRK transcript levels
      were reduced in human colon tumors compared to normal tissue by 35.82%, and
      stable knockdown of SNRK increased colon cancer cell tumorigenicity. Our results
      demonstrate that SNRK is down-regulated in colon cancer and inhibits colon cancer
      cell proliferation through CacyBP up-regulation and beta-catenin degradation,
      resulting in reduced proliferation signaling. These findings reveal a novel
      function for SNRK in the regulation of colon cancer cell proliferation and beta
      catenin signaling.

PMID- 22874834
TI  - Uncovering genes required for neuronal morphology by morphology-based gene trap
      screening with a revertible retrovirus vector.
AB  - The molecular mechanisms of neuronal morphology and synaptic vesicle transport
      have been largely elusive, and only a few of the molecules involved in these
      processes have been identified. Here, we developed a novel morphology-based gene
      trap method, which is theoretically applicable to all cell lines, to easily and
      rapidly identify the responsible genes. Using this method, we selected several
      gene-trapped clones of rat pheochromocytoma PC12 cells, which displayed abnormal
      morphology and distribution of synaptic vesicle-like microvesicles (SLMVs). We
      identified several genes responsible for the phenotypes and analyzed three genes
      in more detail. The first gene was BTB/POZ domain-containing protein 9 (Btbd9),
      which is associated with restless legs syndrome. The second gene was cytokine
      receptor-like factor 3 (Crlf3), whose involvement in the nervous system remains
      unknown. The third gene was single-stranded DNA-binding protein 3 (Ssbp3), a gene
      known to regulate head morphogenesis. These results suggest that Btbd9, Crlf3,
      and Ssbp3 regulate neuronal morphology and the biogenesis/transport of synaptic
      vesicles. Because our novel morphology-based gene trap method is generally
      applicable, this method is promising for uncovering novel genes involved in the
      function of interest in any cell lines.

PMID- 22874835
TI  - Current tobacco use among middle and high school students--United States, 2011.
AB  - Tobacco use continues to be the leading preventable cause of death and disease in
      the United States, with nearly 443,000 deaths occurring annually because of
      cigarette smoking and exposure to secondhand smoke. Moreover, nearly 90% of adult
      smokers begin smoking by age 18 years. To assess current tobacco use among
      youths, CDC analyzed data from the 2011 National Youth Tobacco Survey (NYTS).
      This report describes the results of that analysis, which indicated that, in
      2011, the prevalence of current tobacco use among middle school and high school
      students was 7.1% and 23.2%, respectively, and the prevalence of current
      cigarette use was 4.3%, and 15.8%, respectively. During 2000-2011, among middle
      school students, a linear downward trend was observed in the prevalence of
      current tobacco use (14.9% to 7.1%), current combustible tobacco use (14.0% to
      6.3%), and current cigarette use (10.7% to 4.3%). For high school students, a
      linear downward trend also was observed in these measures (current tobacco use
      [34.4% to 23.2%], current combustible tobacco use [33.1% to 21.0%], and current
      cigarette use [27.9% to 15.8%]). Interventions that are proven to prevent and
      reduce tobacco use among youths include media campaigns, limiting advertisements
      and other promotions, increasing the price of tobacco products, and reducing the
      availability of tobacco products for purchase by youths. These interventions
      should continue to be implemented as part of national comprehensive tobacco
      control programs and should be coordinated with Food and Drug Administration
      (FDA) regulations restricting the sale, distribution, and marketing of cigarettes
      and smokeless tobacco products to youths.

PMID- 22874836
TI  - Interim guidance for clinicians considering the use of preexposure prophylaxis
      for the prevention of HIV infection in heterosexually active adults.
AB  - In the United States, an estimated 48,100 new human immunodeficiency virus (HIV)
      infections occurred in 2009. Of these, 27% were in heterosexual men and women who
      did not inject drugs, and 64% were in men who have sex with men (MSM), including
      3% in MSM who inject drugs. In January 2011, following publication of evidence of
      safety and efficacy of daily oral tenofovir disoproxil fumarate 300 mg
      (TDF)/emtricitabine 200 mg (FTC) (Truvada, Gilead Sciences) as antiretroviral
      preexposure prophylaxis (PrEP) to reduce the risk for HIV acquisition among MSM
      in the iPrEx trial, CDC issued interim guidance to make available information and
      important initial cautions on the use of PrEP in this population. Those
      recommendations remain valid for MSM, including MSM who also have sex with women.
      Since January 2011, data from studies of PrEP among heterosexual men and women
      have become available, and on July 16, 2012, the Food and Drug Administration
      (FDA) approved a label indication for reduction of risk for sexual acquisition of
      HIV infection among adults, including both heterosexuals and MSM. This interim
      guidance includes consideration of the new information and addresses pregnancy
      and safety issues for heterosexually active adults at very high risk for sexual
      HIV acquisition that were not discussed in the previous interim guidance for the
      use of PrEP in MSM.

PMID- 22874837
TI  - Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral
      cephalosporins no longer a recommended treatment for gonococcal infections.
AB  - Gonorrhea is a major cause of serious reproductive complications in women and can
      facilitate human immunodeficiency virus (HIV) transmission. Effective treatment
      is a cornerstone of U.S. gonorrhea control efforts, but treatment of gonorrhea
      has been complicated by the ability of Neisseria gonorrhoeae to develop
      antimicrobial resistance. This report, using data from CDC's Gonococcal Isolate
      Surveillance Project (GISP), describes laboratory evidence of declining cefixime
      susceptibility among urethral N. gonorrhoeae isolates collected in the United
      States during 2006-2011 and updates CDC's current recommendations for treatment
      of gonorrhea. Based on GISP data, CDC recommends combination therapy with
      ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single
      dose or doxycycline 100 mg orally twice daily for 7 days as the most reliably
      effective treatment for uncomplicated gonorrhea. CDC no longer recommends
      cefixime at any dose as a first-line regimen for treatment of gonococcal
      infections. If cefixime is used as an alternative agent, then the patient should
      return in 1 week for a test-of-cure at the site of infection.

PMID- 22874838
TI  - Vital signs: walking among adults--United States, 2005 and 2010.
AB  - BACKGROUND: Physical activity has numerous health benefits, including improving
      weight management. The 2008 Physical Activity Guidelines for Americans recommend
      >=150 minutes/week of moderate-intensity aerobic physical activity (e.g., brisk
      walking) for substantial health benefits. Walking is the most commonly reported
      physical activity by U.S. adults. METHODS: CDC used data from the 2005 and 2010
      National Health Interview Surveys to assess changes in prevalence of walking
      (defined as walking for transportation or leisure in at least one bout of 10
      minutes or more in the preceding 7 days) by sex, age group, race/ethnicity,
      education, body mass index category, walking assistance status, region, and
      physician-diagnosed chronic disease. CDC also assessed the association between
      walking and meeting the aerobic physical activity guideline. RESULTS: Overall,
      walking prevalence increased significantly from 55.7% in 2005 to 62.0% in 2010.
      Significantly higher walking prevalence was observed in most demographic and
      health characteristic categories examined. In 2010, the adjusted odds ratio of
      meeting the aerobic physical activity guideline among walkers, compared with non
      walkers, was 2.95 (95% confidence interval = 2.73-3.19). CONCLUSIONS AND
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: To sustain increases in the prevalence
      of walking, communities can implement evidence-based strategies such as creating
      or enhancing access to places for physical activity, or using design and land use
      policies and practices that emphasize mixed-use communities and pedestrian
      friendly streets. The impact of these strategies on both walking and physical
      activity should be monitored systematically at the national, state, and local
      levels. Public health efforts to promote walking as a way to meet physical
      activity guidelines can help improve the health of U.S. residents.

PMID- 22874839
TI  - The effects of conformation on the noncovalent bonding interactions in a bistable
      donor-acceptor [3]catenane.
AB  - A switchable donor-acceptor bistable [3]catenane, composed of a crown ether
      containing a pair of alternating pi-electron rich tetrathiafulvalene and 1,5
      dioxynaphthalene units, encircled by two pi-electron deficient cyclobis(paraquat
      p-phenylene) rings, has been synthesised and the redox-activated switching it
      undergoes investigated.

PMID- 22874840
TI  - Safety of blood group A2-to-O liver transplantation: an analysis of the United
      Network of Organ Sharing database.
AB  - BACKGROUND: ABO-incompatible organ transplantation typically induces hyperacute
      rejection. A2-to-O liver transplantations have been successful. This study
      compared overall and graft survival in O recipients of A2 and O grafts based on
      Organ Procurement and Transplantation Network data. METHODS: Scientific Registry
      of Transplant Recipients data were used. The first A2-to-O liver transplantation
      was entered on March 11, 1990; all previous transplantations were excluded.
      Between March 11, 1990, and September 3, 2010, 43,335 O recipients underwent
      transplanation, of whom 358 received A2 grafts. RESULTS: There were no
      significant differences in age, sex, and race between the groups. Recipients of
      A2 grafts versus O grafts were significantly more likely to be hospitalized at
      transplantation (45% vs. 38%, P<=0.05) and to have a higher mean (SD) model for
      end-stage liver disease score (24 [11] vs. 22 [10], P<=0.05). 10% of A2
      recipients and 9% of O recipients underwent retransplantation. No significant
      differences existed in rejection during the transplantation admission and at 12
      months: 7% versus 6% and 20% versus 22% for A2 recipients and O recipients,
      respectively; and there were no significant differences in contributing factors
      to graft failure or cause of death. At 5 years, overall survival of A2 and O
      graft recipients was 77% and 74%, respectively (log rank=0.71). At 5 years, graft
      survival was 66% in both groups (log rank=0.52). Donor blood group was
      insignificant on Cox regression for overall and graft survival. CONCLUSIONS:
      Using Organ Procurement and Transplantation Network/Scientific Registry of
      Transplant Recipients data, we present the largest series of A2-to-O liver
      transplantations and conclude this mismatch option to be safe with similar
      overall and graft survival. This opens possibilities to further meet the demands
      of a shrinking organ supply, especially with regard to expanding living-donor
      options.

PMID- 22874841
TI  - Variability in estimated glomerular filtration rate is an independent risk factor
      for death among patients with stage 3 chronic kidney disease.
AB  - Associations between variability of glomerular filtration rate (GFR), death, and
      cardiovascular events have not been reported among patients with chronic kidney
      disease (CKD). In order to evaluate this, we retrospectively analyzed the risk of
      death and de novo heart failure as a function of variability in estimated GFR
      among a cohort of 3361 patients with stage 3 CKD. At baseline, patients with
      greater variability were younger, more likely to have diabetes, hypertension, and
      other comorbid conditions, and were more likely to have proteinuria and higher
      estimated GFR. In multivariate-adjusted Cox proportional hazard models over a
      median follow-up of 3.9 years, the risk of death associated with the highest
      relative to the lowest quartile of variability was 1.40 (95% confidence interval
      1.05-1.87); there was no association with new-onset heart failure. The mortality
      association was independent of serum albumin, proteinuria, baseline estimated
      GFR, and the slope of the estimated GFR. Thus, variability in estimated GFR
      predicts death among patients with stage 3 CKD independent of previously reported
      risk factors. The prognostic utility of complementing existing risk
      stratification metrics with dynamic changes in GFR among patients with CKD
      warrants investigation.

PMID- 22874842
TI  - A reproducible mouse model of chronic allograft nephropathy with vasculopathy.
AB  - Although short-term outcomes in kidney transplantation have improved
      dramatically, long-term survival remains a major challenge. A key component of
      long-term, chronic allograft injury in solid organ transplants is
      arteriosclerosis characterized by vascular neointimal hyperplasia and
      inflammation. Establishing a model of this disorder would provide a unique tool
      not only to identify mechanisms of disease but also to test potential
      therapeutics for late graft injury. To this end, we utilized a mouse orthotopic
      renal transplant model in which C57BL/6J (H-2b) recipients were given either a
      kidney allograft from a completely mismatched Balb/cJ mouse (H-2d) or an isograft
      from a littermate. A unilateral nephrectomy was performed at the time of
      transplant followed by a contralateral nephrectomy on post-transplant day 7.
      Recipients were treated with daily cyclosporine subcutaneously for 14 days and
      then studied 8 and 12 weeks post transplantation. Renal function was
      significantly worse in allograft compared with isograft recipients. Moreover, the
      allografts had significantly more advanced tubulointerstitial fibrosis and
      profound vascular disease characterized by perivascular leukocytic infiltration
      and neointimal hyperplasia affecting the intrarenal blood vessels. Thus, we
      describe a feasible and reproducible murine model of intrarenal transplant
      arteriosclerosis that is useful to study allograft vasculopathy.

PMID- 22874843
TI  - Sodium challenge does not support an acute gastrointestinal-renal natriuretic
      signaling axis in humans.
AB  - A gastrointestinal-renal natriuretic signaling axis has been proposed to regulate
      sodium excretion in response to acute sodium ingestion. Such an axis is thought
      to be regulated by a gastrointestinal sodium sensor coupled to the
      activation/release of a natriuretic signal and could have important clinical and
      scientific implications. Here we systematically tested for this putative axis and
      the potential involvement of the gastrointestinal-derived natriuretic prohormones
      prouroguanylin and proguanylin in 15 healthy volunteers. There was no difference
      in sodium excretion following equivalent oral or intravenous sodium loads during
      either high- or low-sodium diets. Furthermore, serum concentrations of
      prouroguanylin and proguanylin did not increase, did not differ following oral or
      intravenous sodium, and did not correlate with sodium excretion. Thus, our
      results do not support an acute gastrointestinal-renal natriuretic axis or a
      central role for prouroguanylin or proguanylin in humans. If such an axis does
      exist, it is not characterized by a significant difference in the pattern of
      sodium excretion following either an oral or intravenous sodium load.

PMID- 22874844
TI  - Nonthyroidal illness syndrome: is it far away from Crohn's disease?
AB  - GOALS: This study was designed to investigate the clinical features of
      nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn's
      disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical
      outcomes of NTIS patients, and to inspect the correlation of clinical variables
      and NTIS, and their ability of differentiating NTIS from euthyroid patients.
      BACKGROUND: NTIS has been described for more than 30 years. However, only few
      studies focused on the relationship between NTIS and CD. The incidence,
      underlying pathogenesis, clinical outcomes, and correlation with other
      inflammatory disease severity and nutritional variables of NTIS in CD have not
      been completely established. METHODS: Prospectively, 44 CD patients were
      enrolled. Medical records and various laboratory values (including thyroidal,
      nutritional, and inflammatory variables) were collected in all participants.
      RESULTS: The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and
      Chronic Health Evaluation II score, and Crohn's Disease Activity Index score in
      NTIS group were statistically different from those in euthyroid group. A
      decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were
      observed in NTIS group. Duration of hospitalization was significantly longer for
      NTIS patients than euthyroid patients. Albumin was confirmed as a protective
      factor of NTIS in CD. Receiver operating characteristic curve analysis
      demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as
      optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%,
      respectively. CONCLUSIONS: NTIS was a common complication in CD. NTIS patients
      showed worse nutrition status and clinical outcome, and more critical disease
      activity and severity compared with euthyroid patients. A hypodeiodination
      condition and a potential thyroid-hormone-binding dysfunction may play a role in
      the etiology of NTIS in CD. Albumin was a meaningful protective and
      distinguishing marker of NTIS in CD.

PMID- 22874850
TI  - A phase III, randomized controlled study to assess the safety and immunogenicity
      of a semi-synthetic diphtheria, tetanus and whole-cell pertussis vaccine in
      Indian infants.
AB  - BACKGROUND: Reactions to DTwP vaccine are well known and are a matter of great
      concern, much for the development of next generation combination vaccines. To
      avoid such reactions which occur from foreign compounds, WHO suggested
      manufacture of DTwP vaccine using semi-synthetic medium. The phase III trial
      reported here was conducted to assess the immunogenicity, tolerability and safety
      of a new DTwP vaccine manufactured using semi-synthetic medium for both tetanus
      and diphtheria toxoids in comparison with the routinely manufactured DTwP
      vaccine. METHODS: In all, 331 infants aged 6-8 weeks were enrolled, out of which
      308 completed the study. The vaccination was done at 6-10-14 weeks following
      EPI/WHO recommended immunization schedule. Blood samples were collected prior to
      the administration of first dose and one month after the third dose. RESULTS:
      Postvaccination, geometric mean titres for each component did not differ
      significantly amongst the two study groups. Though, the immunogenicity results
      were comparable between the two vaccines, the incidence of adverse events was
      comparatively low in semi-synthetic vaccine as against the routine vaccine group
      for all the three doses. CONCLUSIONS: The semi-synthetic DTwP vaccine was
      immunogenic and showed a significant lower incidence of local adverse events in
      comparison to the routine vaccine. This vaccine is now being used in the routine
      vaccination programme both as a triple antigen (DTwP alone) as well as a
      combination with Hepatitis B and/or Haemophilus influenzae type b vaccine.

PMID- 22874851
TI  - Disability among US Army Veterans vaccinated against anthrax.
AB  - CONTEXT: To protect troops against the use of anthrax as a biological weapon, the
      US Department of Defense began an anthrax vaccination program in 1998. 14 years
      after the inception of the vaccination program, there is no evidence suggesting
      vaccination against anthrax carries long-term health risks for Active Duty
      Soldiers. OBJECTIVE: To investigate the association between Anthrax Vaccine
      Adsorbed (AVA) received while on Active Duty and subsequent disability determined
      by the Veterans Benefits Administration. DESIGN, SETTING AND PARTICIPANTS: Case
      control study nested in the cohort of all Active Duty personnel known to have
      separated from the US Army between December 1, 1997 and December 31, 2005. Cases
      were >=10% disabled, determined either by the Army prior to separation (N=5846)
      or by the Veterans Benefits Administration (VBA) after separation (N=148,934).
      Controls (N=937,705) separated from the Army without disability, and were not
      receiving pensions from the VBA as of April 2007. Data were from the Total Army
      Injury and Health Outcomes Database and the VBA Compensation and Pension and
      Benefits database. MAIN OUTCOMES: Disability status (yes/no); for primary
      disability, percent disabled (>=10%, 20%, >20%) and type of disability. RESULTS:
      Vaccination against anthrax was four times more likely among disabled Veterans
      with hostile fire pay records (HFP, a surrogate for deployment). Vaccinated
      Soldiers with HFP had lower odds of disability separation from the Army 0.89
      (0.80, 0.98); there was no association between vaccine and receiving Army
      disability benefits among those without HFP (OR=1.05, CI: 0.96, 1.14).
      Vaccination was negatively associated with receiving VA disability benefits for
      those with HFP (OR=0.66, CI: 0.65, 0.67), but there was little or no association
      between vaccine and receipt of VA disability benefits for those without HFP
      (OR=0.95, CI: 0.93, 0.97). CONCLUSIONS: Risk of disability separation from the
      Army and receipt of disability compensation from the VA were not increased in
      association with prior exposure to AVA. This study provides evidence that
      vaccination against anthrax is not associated with long term disability.

PMID- 22874845
TI  - The dynamics of protein-protein interactions between domains of MscL at the
      cytoplasmic-lipid interface.
AB  - The bacterial mechanosensitive channel of large conductance, MscL, is one of the
      best characterized mechanosensitive channels serving as a paradigm for how
      proteins can sense and transduce mechanical forces. The physiological role of
      MscL is that of an emergency release valve that opens a large pore upon a sudden
      drop in the osmolarity of the environment. A crystal structure of a closed state
      of MscL shows it as a homopentamer, with each subunit consisting of two
      transmembrane domains (TM). There is consensus that the TM helices move in an
      iris like manner tilting in the plane of the membrane while gating. An N-terminal
      amphipathic helix that lies along the cytoplasmic membrane (S1), and the portion
      of TM2 near the cytoplasmic interface (TM2(ci)), are relatively close in the
      crystal structure, yet predicted to be dynamic upon gating. Here we determine how
      these two regions interact in the channel complex, and study how these
      interactions change as the channel opens. We have screened 143 double-cysteine
      mutants of E. coli MscL for their efficiency in disulfide bridging and generated
      a map of protein-protein interactions between these two regions. Interesting
      candidates have been further studied by patch clamp and show differences in
      channel activity under different redox potentials; the results suggest a model
      for the dynamics of these two domains during MscL gating.

PMID- 22874852
TI  - The pediatric vaccine stockpiling problem.
AB  - The U.S. has experienced many major interruptions of its pediatric vaccine
      production in the past decade. The Centers for Disease Control and Prevention
      (CDC) copes with these shortages by building a national stockpile of pediatric
      vaccines, which it makes accessible to the public in the event of a shortage. The
      management of this stockpile is difficult due to limited production capacity and
      long and unpredictable production interruptions. In this paper, we address
      policies for managing the stockpile. We provide sufficient conditions for the
      optimal policy to be a modified state-dependent base-stock policy, with the base
      stock level decreasing in the pipeline inventory. Since the optimal policy is in
      general difficult to evaluate, we derive bounds on the optimal decision in each
      period. We develop an efficient policy that performs on average within 1% of
      optimality in simulations. We show that stocking the same supply of vaccine of
      every type can be over-conservative in some cases, and inadequate in others by
      large factors. We also quantify the substantial reduction in inventory level that
      can be achieved when there are multiple suppliers in the market.

PMID- 22874853
TI  - Influence of parent graphite particle size on the electrochemistry of thermally
      reduced graphene oxide.
AB  - Electrochemical applications of graphene are of very high importance. For
      electrochemistry, bulk quantities of materials are needed. The most common
      preparation of bulk quantities of graphene materials is based on oxidation of
      graphite to graphite oxide and subsequent thermal exfoliation of graphite oxide
      to thermally reduced graphene oxide (TR-GO). It is important to investigate to
      which extent a reaction condition, that is, composition of the oxidation mixture
      and size of graphite materials, influences the properties of the resulting
      materials. We characterised six graphite materials with a range of particle sizes
      (0.05, 11, 20, 32, 35 and 41 MUm) and the TR-GO products prepared from them by
      use of scanning electron microscopy, Raman spectroscopy and X-ray photoelectron
      spectroscopy. Cyclic voltammetric performance of the TR-GO samples was compared
      using ferro/ferricyanide and ascorbic acid. We observed no correlation between
      size of initial graphite and properties of the resultant TR-GO such as density of
      surface defects, amount of oxygen-containing groups, or rate of heterogeneous
      electron transfer (HET). A positive correspondence between HET rate and high
      defect density as well as low amounts of oxygen functionalities was noted. Our
      findings will have profound influence upon practical fabrication of graphene for
      applications in sensing and energy storage devices.

PMID- 22874854
TI  - Granule cell dispersion is associated with memory impairment in right mesial
      temporal lobe epilepsy.
AB  - PURPOSE: We analyzed the association of granule cell dispersion (GCD) with memory
      performance, clinical data and surgical outcome in a series of patients with
      mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS). METHOD:
      Hippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and
      27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD
      groups and thirteen controls were studied. Quantitative neuropathological
      evaluation was performed using hippocampal sections stained with NeuN. Patients'
      neuropsychological measures, clinical data, type of MTS and surgical outcome were
      reviewed. RESULTS: GCD occurred in 28 (51.9%) patients. No correlation between
      GCD and MTS pattern, clinical data or surgical outcome was found. The presence of
      GCD was correlated with worse visuospatial memory performance in right MTLE, but
      not with memory performance in left MTLE. CONCLUSION: GCD may be related to
      memory impairment in right MTLE-MTS patients. However, the role of GCD in memory
      function is not precisely defined.

PMID- 22874855
TI  - The absence of regulation: cause for concern.

PMID- 22874856
TI  - Erectile dysfunction:  a new plague.
AB  - Erectile dysfunction has the potential to affect all men, of all ages and of all
      ethnicities, it does not discriminate. It has the power to emasculate men,
      impacting on their daily lives.

PMID- 22874857
TI  - Lymphoedema treatment in palliative care: a case study.
AB  - This article will focus on the evidence to support the treatment of a palliative
      patient who was diagnosed with cancer-related secondary lymphoedema. A case study
      approach has been adopted, which focuses on the anatomy and physiology  of
      lymphoedema and how this is treated through an analysis of the treatment
      regimens. To establish the effectiveness of these treatment regimes, the use of
      objective and subjective tools will also be analysed to ascertain their
      importance within care. The findings of this case study and the supporting
      evidence indicate a positive correlation between the use of lymphoedema treatment
      methods in both limb volume reduction and quality-of-life outcomes. However,
      robust evidence is  required to expand the importance of each treatment used in
      the area of lymphoedema management.

PMID- 22874858
TI  - Reconstruction for breast  cancer in a nutshell.
AB  - Breast cancer is a disease many will experience. Depending on the size of the
      cancer, the size of the host breast, and whether it is multi-focal, a mastectomy
      may be recommended as part of the treatment. If this is the case, an immediate
      breast reconstruction may be offered. This article will describe the three main
      types of breast reconstruction and discuss pertinent issues regarding this,
      including complications, surgery to the other (contraleteral) breast and
      potential psychological implications of this surgery.

PMID- 22874859
TI  - Does nurses' vulnerability  affect their ability to care?
AB  - Recent reports from the Department of Health (2008), the Parliamentary and Health
      Service Ombudsman (2011) and the Commission on Dignity in Care for Older People
      (2012) have been highly critical regarding the care that some patients have
      experienced. They have highlighted that fundamental aspects of care are missing
      resulting in a lack of high quality individualised nursing care, which is in
      contrast with holistic nursing philosophy. We have to ask ourselves what is
      happening within nursing, as many enter the profession owing to a desire to 'make
      a difference'. Drawing on focus group data exploring perceptions of caring for
      residents with dementia in a care home setting, the authors found that nurses and
      healthcare assistants experience a mutual vulnerability with patients. This paper
      explores whether this mutual vulnerability could lead to nurses focusing on the
      clinical aspects of their role to the detriment of the compassionate, caring
      components of nursing.

PMID- 22874860
TI  - Work-based learning  in health and social care.
AB  - This article examines some of the issues encountered in helping to develop and
      facilitate work-based learning (WBL) in clinical areas from the author's
      perspective of APEL/WBL co-ordinator. The advantages of work-based learning to
      both organisations and practitioners are discussed, together with possible
      drawbacks. The article concludes by identifying the positive aspects, including
      that of practice development, but suggests caution in attempting to use work
      based learning in all circumstances.

PMID- 22874861
TI  - Nursing students' views of clinical competence assessment.
AB  - This paper reports on some outcomes of a research study evaluating a new
      assessment framework of clinical competence used in undergraduate nursing
      programmes in the Mid West Region of Ireland. First, this paper presents both the
      strengths and weaknesses of the present model, as articulated by student nurses.
      Second, it generates a broader critical debate around the concept of competency
      assessment. The model of competence in question was developed by the Irish
      Nursing Board then elaborated on by the University of Limerick in partnership
      with local health service providers in 2002. Methodology involved a triangulated
      approach, comprising a series of focus group interviews with students (n=13) and
      preceptors (n=16) followed by a survey of students (n=232) and preceptors
      (n=837). Findings from the student focus groups are reported here. Themes
      identified using Burnard's (1991) framework for analysis are preparation for
      competency assessment, competency documentation, supporting assessment in
      practice, organisational and resource factors and the competency assessment
      structure and process. Results from this research have implications for
      refinement and revision of the present competency assessment framework, for
      student and staff preparation and for collaboration between stakeholders.

PMID- 22874862
TI  - Medication administration practices among children's nurses: a survey.
AB  - AIM AND OBJECTIVES: The overall aim of this study was to investigate the
      medication administration practices of children's nurses. The specific objective
      was to identify practices that may improve the medication administration process,
      where necessary. DESIGN: Using a non-experimental survey design, a 'Medication
      Administration Practices Survey' was developed for use in this study. The survey
      was designed to include questions based on medication administration practices
      and not solely on medication errors. Ethical approval was obtained from the local
      research ethics committee where data were collected. All clinical staff working
      in all areas in a children's hospital were included. RESULTS: Interruptions in
      the medication process, a heavy workload and fatigue were some of the findings
      that emerged from this study. Inadequate knowledge and skills and a failure to
      comply with hospital policy were also identified. CONCLUSION: A lack of adherence
      to hospital policy and the frequency of interruptions in the medication
      administration process are important practices that require change as indicated
      by this study. Several recommendations are made, directed toward preventing or
      reducing medication errors and supporting children's nurses in providing best
      practice.

PMID- 22874863
TI  - Opening ceremonies celebrate nurses.
AB  - The opening ceremonies of what many consider the greatest show on earth took
      place on Friday 27 July and hundreds of nurses took part. Many were chosen for a
      special sequence dedicated to NHS workers. Others, however, were chosen to
      interact with audience members as a result of some of the same attributes that
      make nurses uniquely qualified to deliver patient care. Kath Lynch, a clinical
      lead nurse at the Royal Free Travel Health Centre, was one of the selected few
      and was even honoured for her enthusiasm with four real Olympic medals.

PMID- 22874864
TI  - Nurses contribute  to world-class care in Athletes' Village.

PMID- 22874865
TI  - Health Foundation report calls for a better model of patient interaction.

PMID- 22874866
TI  - Looking for a hero: nurses' caring efforts to be rewarded.
AB  - Professor Alan Glasper discusses the new NHS Heroes scheme, which is designed to
      recognise the efforts of local staff, such as nurses, whose expertise and passion
      for care helps maintain and nurture the spirit of the NHS.

PMID- 22874867
TI  - Professors of nursing: academic equity or professional enigma?

PMID- 22874868
TI  - Safeguarding patients  as a student nurse.
AB  - Emma Louise Botten is a second-year nursing student at King's College London and
      a regular contributor to the BJN Student Column. In this issue, Emma emphasises
      the importance of your role as a student nurse in safeguarding your patients. She
      provides an overview of resources available to student nurses and some practical
      tips she has gathered from her own experience.

PMID- 22874869
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 5: patient
      education.

PMID- 22874870
TI  - A look at the health of nurses: 'get on your bike?'.

PMID- 22874871
TI  - Synthesis and biological evaluation of unprecedented ring-expanded nucleosides
      (RENs) containing the imidazo[4,5-d][1,2,6]oxadiazepine ring system.
AB  - A small collection of ring-expanded nucleosides (RENs), containing the
      unprecedented bis-alkylated imidazo[4,5-d][1,2,6]oxadiazepine heterocyclic ring
      system, has been synthesized through a new general approach. Results of
      preliminary cytotoxicity tests on breast (MCF-7) and lung (A549) cancer cell
      lines are also reported.

PMID- 22874873
TI  - Lead in drinking water and human blood lead levels in the United States.
AB  - Lead is a pervasive environmental contaminant. The adverse health effects of lead
      exposure in children and adults are well documented, and no safe blood lead
      threshold in children has been identified. Lead can be ingested from various
      sources, including lead paint and house dust contaminated by lead paint, as well
      as soil, drinking water, and food. The concentration of lead, total amount of
      lead consumed, and duration of lead exposure influence the severity of health
      effects. Because lead accumulates in the body, all sources of lead should be
      controlled or eliminated to prevent childhood lead poisoning. Beginning in the
      1970s, lead concentrations in air, tap water, food, dust, and soil began to be
      substantially reduced, resulting in significantly reduced blood lead levels
      (BLLs) in children throughout the United States. However, children are still
      being exposed to lead, and many of these children live in housing built before
      the 1978 ban on lead-based residential paint. These homes might contain lead
      paint hazards, as well as drinking water service lines made from lead, lead
      solder, or plumbing materials that contain lead. Adequate corrosion control
      reduces the leaching of lead plumbing components or solder into drinking water.
      The majority of public water utilities are in compliance with the Safe Drinking
      Water Act Lead and Copper Rule (LCR) of 1991. However, some children are still
      exposed to lead in drinking water. EPA is reviewing LCR, and additional changes
      to the rule are expected that will further protect public health. Childhood lead
      poisoning prevention programs should be made aware of the results of local public
      water system lead monitoring measurement under LCR and consider drinking water as
      a potential cause of increased BLLs, especially when other sources of lead
      exposure are not identified.

PMID- 22874874
TI  - Palliative care and hematologic oncology: the promise of collaboration.
AB  - Palliative medicine provides active evaluation and treatment of the physical,
      psychosocial and spiritual needs of patients and families with serious illnesses,
      regardless of curability or stage of illness. The hematologic malignancies
      comprise diverse clinical presentations, evolutions, treatment strategies and
      clinical and quality of life outcomes with dual potential for rapid clinical
      decline and ultimate improvement. While recent medical advances have led to cure,
      remission or long-term disease control for patients with hematologic malignancy,
      many still portend poor prognoses and all are associated with significant symptom
      and quality of life burden for patients and families. The gravity of a diagnosis
      of a hematologic malignancy also weighs heavily on the medical team, who
      typically develop close and long-term relationships with their patients.
      Palliative care teams provide an additional layer of support to patients, family
      caregivers, and the primary medical team through close attention to symptoms and
      emotional, practical, and spiritual needs. Barriers to routine palliative care co
      management in hematologic malignancies include persistent health professional
      confusion about the role of palliative care and its distinction from hospice;
      inadequate availability of palliative care provider capacity; and widespread lack
      of physician training in communicating about achievable goals of care with
      patients, family caregivers, and colleagues. We herein review the evidence of
      need for palliative care services in hematologic malignancy patients in the
      context of a growing body of evidence demonstrating the beneficial outcomes of
      such care when provided simultaneously with curative or life-prolonging
      treatment.

PMID- 22874875
TI  - Traditional nurse instruction versus 2 session nurse instruction plus DVD for
      teaching ostomy care: a multisite randomized controlled trial.
AB  - PURPOSE: This randomized controlled trial compared 2 methods of ostomy care
      instruction to determine their effect on patients' knowledge, skills, and
      confidence related to postoperative ostomy care. SUBJECTS AND SETTING: Eighty
      eight adults with newly created ostomies were randomly assigned to 1 of 2 groups.
      Of the 88 enrolled patients, 68 completed the study: 10 patients were discharged
      from the hospital prior to completion of the study interventions; 10 others were
      withdrawn because they no longer met study inclusion criteria. The remaining
      subjects, who were equally split between men and women, ranged in age from 23 to
      84 years. There were 23 colostomy and 45 ileostomy patients in our sample. The
      study setting was 2 acute care hospitals within a large tertiary health care
      system in the midwestern United States. METHODS: We used a posttest-only
      experimental design to compare 2 methods of postoperative ostomy education.
      Traditional education comprised 3 WOC nurse-led instruction sessions and the
      experimental intervention comprised 2 nurse-led instruction sessions plus DVD
      instruction that could be accessed in between nurse-led sessions. All patients
      received one-on-one instruction from certified WOC nurse at their bedside.
      Patients completed a written test of ostomy knowledge, a self-care skills
      demonstration, and a Visual Analog Scale rating their confidence with ostomy self
      care. RESULTS: There were no significant differences between the 2 teaching
      methods or type of ostomy with regard to knowledge of ostomy care (F3,64 5 1.308,
      P 5 0.28), ostomy care skills (F3,64 5 0.163, P 5 0.92), or confidence in
      performing ostomy self-care (F3,64 5 0.629, P 5 0.59). Differences between the
      study groups' self-reported learning style, education level, age, room type, and
      gender also did not significantly impact their knowledge, skills, or confidence.
      CONCLUSION: When teaching first-time ostomy patients postoperative self-care, a
      Nurse Instruction plus DVD method is as effective as Nurse Instruction alone.

PMID- 22874876
TI  - Incidence of pediatric diarrhea and public-private preferences for treatment in
      rural Myanmar: a randomized cluster survey.
AB  - The incidence of pediatric diarrhea in countries neighboring Myanmar is high
      (>9%). No national data exist in Myanmar, however hospital treatment data
      indicate that diarrhea is a major cause of morbidity. OBJECTIVE: This study seeks
      to determine diarrhea incidence among children in rural Myanmar and document
      health-seeking behavior and treatment costs. METHODS: We surveyed 2033 caregivers
      in households with under-five children, in 104 randomly selected villages in
      rural Myanmar. FINDINGS: The incidence of diarrhea in the 2 weeks prior to the
      survey was 4.9%. Home treatment was common (50.6%); among those who consulted a
      professional 35.6% went to government clinics, 28.8% to private clinics and 28.0%
      to a community health worker. The cost of treatment was highest ($15) at
      government clinics and lowest ($1.3) for self-treatment at home. CONCLUSION:
      Pediatric diarrhea is an important cause of morbidity in rural Myanmar. Self
      treatment and treatment by private providers is common.

PMID- 22874877
TI  - Role and potential for therapeutic targeting of MYB in leukemia.
AB  - The Myb protein was first identified as an oncogene that causes leukemia in
      chickens. Since then, it has been widely associated with different types of
      cancers and studied in detail in myeloid leukemias. However, despite these
      studies, its role in the induction, pathogenesis and maintenance of AML, and
      other blood disorders, is still not well understood. Recent efforts to uncover
      its plethora of transcriptional targets have provided key insights into
      understanding its mechanism of action. This review evaluates our current
      knowledge of the role of Myb in leukemia, with a particular focus on AML, from
      the vast literature spanning three decades, highlighting key studies that have
      influenced our understanding. We discuss recent insights into its role in
      leukemogenesis and how these could be exploited for the therapeutic targeting of
      Myb, its associated co-regulators or its target genes, in order to improve
      outcomes in the treatment of a wide range of hematopoietic malignancies.

PMID- 22874879
TI  - Development of an Aeromonas hydrophila recombinant extracellular protease
      vaccine.
AB  - Aeromonas hydrophila (Ah) exists widely in the aquatic environment and infects a
      variety of animals. Extracellular protease (EPR) is an important protective
      antigen that induces a specific antibody response to resist Ah infection. In this
      study, two genes encoding extracellular protease epr2 and epr3 were linked within
      the expression vector pET32a to construct a recombinant pET-epr2-3 plasmid. The
      immunogenicity of the fusion protein epr2-3 was investigated as a subunit vaccine
      in ICR mice. The recombinant epr2-3 protein induced the production of high
      antibody titers. The survival rate against homogenous Ah J-1 challenge was
      significantly higher in the epr2-3 vaccinated group (>=80%) compared with the
      inactivated Ah vaccinated group and the challenge control group (P < 0.01), thus
      indicating that the recombinant epr2-3 protein provided significant protection
      against Ah infection. Therefore, the recombinant epr2-3 is a promising candidate
      for development as a vaccine against Ah infections.

PMID- 22874880
TI  - The test-retest reliability of 10 meters maximal walking speed in older people
      living in a residential care unit.
AB  - BACKGROUND AND PURPOSE: It is very important to analyze and estimate physical
      limitations in older people to prevent falls and further physical decline.
      Walking speed can be used as an outcome measure for evaluating a physical
      exercise program, but to do so, relative and absolute reliability need to be
      established. No studies have evaluated the reliability of maximal walking speed
      in an aged population with different medical diagnoses. Therefore, the aim of
      this study was to investigate the reliability of walking speed through test
      retest in older people living in a residential care unit. METHODS: A sample of
      older people living in a residential care unit was invited to participate in the
      study. Maximal walking speed was measured for a distance of 10 m with an
      acceleration and deceleration phase of 2 m each. Data were collected twice for
      each individual within a 1-week interval. RESULTS: Thirty-one subjects
      participated on both test occasions. The mean age was 89 years (74-100 years); 25
      women and 6 men participated. The test-retest analysis showed an intraclass
      correlation coefficient (1,1) of 0.86 between the 2 tests. The mean value of the
      first occasion was 0.97 m/s (SD = 0.30 m/s), and the mean value of the second
      occasion was 0.95 m/s (SD = 0.29 m/s). The mean difference was -0.03 m/s (SD =
      0.16 m/s), and the 95% limits of agreement for the mean difference were -0.33 to
      0.27. DISCUSSION AND CONCLUSION: A maximum walking speed test in institution
      dwelling older people aged 65 years and older, with several different diagnoses,
      shows high reliability. The method is easy to perform in a clinical setting at a
      minimal cost and can be recommended for use in this group before and after a
      training period. However, the variance of -0.33 to +0.27 m/s needs to be
      considered when evaluating the effect of a training period.

PMID- 22874881
TI  - The intricate paramagnetic state of [Os(Q)2(bpy)]+, Q = 4,6-di-tert-butyl-o
      iminobenzoquinone.
AB  - The combination of two highly non-innocent ligands with a third-row transition
      metal produces the title complex ion which was crystallised as
      [Os(Q)(2)(bpy)](ClO(4)).C(6)H(6) (Q = 4,6-di-tert-butyl-o-iminobenzoquinones, bpy
      = 2,2'-bipyridine) and could be structurally characterised to exhibit a tris
      chelate situation at the metal with trans-positioned N and cis-positioned O donor
      atoms. The metrical ligand parameters are in agreement with two partially reduced
      ligands. A 3-spin interaction (Q(-))Os(III)(Q(-)) can rationalise the observed S
      = 1/2 situation with ligand-centred resulting spin. Ligand-based spin is
      confirmed by DFT (calculated spin populations Q: 1.113; Os: -0.113; bpy: 0.001)
      and is also apparent from the EPR signal (g(1) 1.981, g(2) 1.955, g(3) 1.803,
      Deltag 0.178, <g> 1.915) which is influenced by the high spin-orbit coupling
      constant of the osmium centre. The susceptibility measurements reveal
      antiferromagnetic behaviour. A one-electron oxidation and two one-electron
      reductions could be monitored spectroelectrochemically (UV-VIS-NIR) and analysed
      by TD-DFT, in comparison with the results from the ruthenium analogue. The
      analysis reflects the strong orbital mixing between the metal and the two Q
      ligand MOs.

PMID- 22874878
TI  - Minor clone provides a reservoir for relapse in multiple myeloma.
AB  - Recent studies have provided direct evidence for genetic variegation in subclones
      for various cancer types. However, little is known about subclonal evolutionary
      processes according to treatment and subsequent relapse in multiple myeloma (MM).
      This issue was addressed in a cohort of 24 MM patients treated either with
      conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is
      a highly heterogeneous disease associated with a large number of chromosomal
      abnormalities, a subset of secondary genetic events that seem to reflect
      progression, 1q21 gain, NF-kappaB-activating mutations, RB1 and TP53 deletions,
      was examined. By using high-resolution single-nucleotide polymorphism arrays,
      subclones were identified with nonlinear complex evolutionary histories. Such
      reordering of the spectrum of genetic lesions, identified in a third of MM
      patients during therapy, is likely to reflect the selection of genetically
      distinct subclones, not initially competitive against the dominant population but
      which survived chemotherapy, thrived and acquired new anomalies. In addition, the
      emergence of minor subclones at relapse appeared to be significantly associated
      with bortezomib treatment. These data support the idea that new strategies for
      future clinical trials in MM should combine targeted therapy and subpopulations'
      control to eradicate all myeloma subclones in order to obtain long-term
      remission.

PMID- 22874882
TI  - Arsenic exposure and tobacco consumption: Biomarkers and risk assessment.
AB  - Arsenic is measurable in tobacco and cigarette mainstream smoke (MSS). Whether
      arsenic has an independent role in diseases associated with tobacco consumption
      is not known. Epidemiology and biomonitoring data and probabilistic risk
      assessment (PRA) methods were used to investigate this potential association.
      Analysis of data from the National Health and Nutrition Examination Survey
      (NHANES) showed that urine arsenic concentrations in tobacco consumers were not
      different or were lower than levels in non-consumers of tobacco. Additionally,
      urine arsenic levels from NHANES tobacco consumers were five-times or more lower
      than levels reported in epidemiology studies to be associated with adverse health
      effects. Results of PRA indicated that mean non-cancer hazard estimates and mean
      incremental lifetime cancer risk estimates were within accepted ranges. Taken
      together, these results suggest that arsenic may not be independently associated
      with tobacco consumption or diseases related to tobacco consumption.

PMID- 22874883
TI  - Adaptive thresholding algorithm based on SAR images and wind data to segment oil
      spills along the northwest coast of the Iberian Peninsula.
AB  - Satellite Synthetic Aperture Radar (SAR) has been established as a useful tool
      for detecting hydrocarbon spillage on the ocean's surface. Several surveillance
      applications have been developed based on this technology. Environmental
      variables such as wind speed should be taken into account for better SAR image
      segmentation. This paper presents an adaptive thresholding algorithm for
      detecting oil spills based on SAR data and a wind field estimation as well as its
      implementation as a part of a functional prototype. The algorithm was adapted to
      an important shipping route off the Galician coast (northwest Iberian Peninsula)
      and was developed on the basis of confirmed oil spills. Image testing revealed
      99.93% pixel labelling accuracy. By taking advantage of multi-core processor
      architecture, the prototype was optimized to get a nearly 30% improvement in
      processing time.

PMID- 22874884
TI  - End-of-life care in the treatment of advanced heart failure in the elderly.
AB  - Heart failure presents its own unique challenges to the clinician who desires to
      make excellent and humane care near the end of life a tangible reality. Accurate
      prediction of mortality in the individual patient is complicated by both the
      frequent occurrence of sudden death, both with and without devices, and the
      frequently chronic course that is punctuated by recurrent and more prominent
      acute episodes. A significant literature demonstrates that healthcare providers
      continue to have difficulty communicating effectively with terminally ill
      patients and their caregivers regarding end-of-life care preferences, and it is
      clear from the prognostic uncertainty of advanced heart failure that this kind of
      communication, and discussions regarding palliative care, need to occur earlier
      rather than later. This article discusses various means of providing palliative
      care, and specific issues regarding device therapy, cardiopulmonary
      resuscitation, and palliative sedation, with concurrent discussion of the ethical
      ramifications and pitfalls of each. A recent scientific statement from the
      American Heart Association begins to address some of the methodological issues
      involved in the care of patients with advanced heart failure. Above all,
      clinicians who wish to provide the highest quality of care to the dying patient
      need to confront the existential reality of death in themselves, their loved
      ones, and their patients so as to best serve those remanded to their care.

PMID- 22874885
TI  - Statin loading before percutaneous coronary intervention to reduce periprocedural
      myocardial infarction.
AB  - Periprocedural myocardial infarction (PMI) is a common complication associated
      with percutaneous coronary intervention (PCI), occurring in approximately 15% to
      20% of patients undergoing the procedure. The established diagnostic criteria for
      PMI is an increase in cardiac biomarkers, specifically creatine kinase-MB levels
      > 3 times the upper limit of normal. As PMI has been associated with an increased
      risk of mortality after PCI, investigative efforts have been directed at
      therapies that can potentially decrease PMI. One such therapy is the use of
      hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) administered as a
      loading dose before PCI. Multiple small, randomized, controlled trials have
      demonstrated significant reductions in the incidence of PMI with statin loading
      before PCI. The risk reduction was seen in patients with stable and unstable
      coronary artery disease, as well in statin-naive patients or those on chronic
      statin therapy. Potential mechanisms for the rapid benefits of statin loading
      include: anti-inflammatory effects, reversal of endothelial dysfunction, decrease
      in oxidative stress, and inhibition of the thrombotic system. None of the current
      studies were of sufficient power or duration to detect benefits on mortality,
      though a recent meta-analysis did demonstrate a reduction in major adverse
      cardiovascular events. In addition to long-term effects, several additional
      questions remain with regard to statin loading, such as statin type, dose, and
      optimal timing of administration. However, given the current evidence of benefit
      and the low risk of adverse events, it can be recommended that all patients
      undergoing PCI be considered for statin loading before the procedure.

PMID- 22874886
TI  - Multifocal CNS demyelination after octreotide treatment for metastatic
      meningioma.

PMID- 22874887
TI  - Rosai-Dorfman disease presenting as cervical radiculopathy.

PMID- 22874888
TI  - Primary intraventricular-trigonal choriocarcinoma.

PMID- 22874889
TI  - Outcome associations of carotid-femoral pulse wave velocity vary with different
      measurement methods.
AB  - BACKGROUND: The impact of various methods of travel distance estimation on the
      prognostic value of pulse wave velocity (PWV) and on the adequacy of cut-offs has
      never been addressed within a single population of hypertensive patients.
      METHODS: Four carotid-femoral PWVs were calculated from four different travel
      distances (Direct, Real, Subtracted, and Estimated) divided by the same travel
      time in 426 hypertensives (mean age 51.2 +/- 13.8 years, mean systolic blood
      pressure 155.6 +/- 21.1 mm Hg). The incidence of death from any cause and major
      cardiovascular events was studied. PWV predictive accuracies were determined
      using C-index analysis. Hazard ratios (HRs) associated with specific values of
      PWV were determined with Cox model analyses using cubic splines. RESULTS: Mean
      PWV ranged from 8.3 +/- 2.3 m/s for the Subtracted one to 11.6 +/- 3.0 m/s for
      the Direct one (P < 0.001). When included as continuous variables in a Cox model,
      the four PWVs were significantly associated with outcome (all P < 0.001), and had
      similar C-index (0.608-0.617). In multivariable analysis, the HR calculated for a
      Direct PWV of 12 m/s was neutral (HR = 1.02). In contrast, the same analysis
      provided HR ranging from 1.79 to 2.90 with the other PWVs. CONCLUSIONS: Different
      travel distances markedly impact PWV values and prognostic cut-offs. PWV cut-offs
      should consequently be ascertained jointly with the method of measurement used.
      There is an urgent need for standardization of PWV assessment before implementing
      this parameter in the routine management of hypertensives.

PMID- 22874890
TI  - Association of renal resistive index with target organ damage in essential
      hypertension.
AB  - BACKGROUND: The renal resistive index (RI) measured using Doppler ultrasonography
      has been used as a diagnostic tool in the daily work-up of kidney diseases. A
      better understanding of its relationship with preclinical organ damage may help
      in determining overall cardiovascular risk in hypertensive patients. METHODS: We
      evaluated the association between RI and the presence and degree of target organ
      damage (TOD) in 288 (130 male) essential hypertensive patients. RI, carotid
      intima-media thickness (IMT), and left ventricular (LV) mass index were assessed
      by ultrasound scan. Albuminuria was measured as the albumin-to-creatinine ratio
      (ACR) in three consecutive first morning urine samples. RESULTS: In univariate
      analysis, patients with TOD showed significantly higher RI as compared with those
      without TOD (presence vs. absence of carotid wall thickening, LV hypertrophy, and
      albuminuria, P < 0.01, respectively). The severity of each TOD increased
      progressively from the lower to the upper RI tertile. Multiple logistic
      regression analysis found that each standard deviation increase in RI gave a 47%
      higher odds of having LV hypertrophy, and a 70% higher odds of having albuminuria
      (P < 0.05, respectively). The occurrence of at least two signs of TOD also
      significantly increased in parallel with elevation of RI (odds ratio (OR): 1.89
      for 1 s.d. increase, P < 0.01). CONCLUSIONS: These results suggest that increased
      RI may be a marker of subclinical TOD in patients with essential hypertension.

PMID- 22874891
TI  - Measurement of central aortic pulse pressure: noninvasive brachial cuff-based
      estimation by a transfer function vs. a novel pulse wave analysis method.
AB  - BACKGROUND: The prognostic value of central aortic pulse pressure (PP-C) may have
      been underestimated due to its measurement inaccuracy. We aimed to investigate
      the accuracy of noninvasive brachial cuff-based estimation of PP-C by a
      generalized transfer function (GTF) or a novel pulse wave analysis (PWA) approach
      to directly estimate PP-C. METHODS: Invasive high-fidelity right brachial and
      central aortic pressure tracings, and left brachial pulse volume plethysmography
      (PVP) waveforms from an oscillometric blood pressure (BP) monitor were all
      digitized simultaneously in 40 patients during cardiac catheterization. An aortic
      to-brachial GTF and a PWA multivariate prediction model using the PVP waveforms
      calibrated to brachial cuff systolic BP (SBP) and diastolic BP(DBP) were
      constructed. Accuracy of the two methods was examined in another 100 patients
      against invasively measured PP-C. RESULTS: The error of cuff PP in estimating PP
      C was 1.8 +/- 12.4 mm Hg. Application of the GTF on noninvasively calibrated PVP
      waveforms produced reconstructed aortic pressure waves and PP-C estimates with
      errors of -3.4 +/- 11.6 mm Hg (PP-C = reconstructed aortic SBP - aortic DBP) and 
      2.3 +/- 11.4 mm Hg (PP-C = reconstructed aortic SBP - cuff DBP), respectively.
      The observed systematic errors were proportional to the magnitudes of PP-C. In
      contrast, the error of the PWA prediction model was 3.0 +/- 7.1 mm Hg without
      obvious proportional systematic error. CONCLUSIONS: Large random and systematic
      errors are introduced into the PP-C estimates when PP-C is calculated as the
      difference between the estimated central SBP and central or cuff DBP. The
      accuracy can be improved substantially with the novel PWA approach.

PMID- 22874893
TI  - The reliability of detecting digital dermatitis in the milking parlour.
AB  - Digital dermatitis (DD) is currently the most problematic infectious skin disease
      in dairy cattle associated with lameness. Reducing the disease prevalence through
      early detection and treatment is an essential management tool. The traditional
      detection method involves lifting and inspecting the feet in a cattle crush, but
      this is a time intensive and costly practice and impractical for regular
      detection of individual cases or monitoring herd prevalence. This study aimed to
      establish the accuracy of detecting and classifying DD lesions in traditional
      (pit) milking parlours compared with a borescope, and a gold standard lifted foot
      inspection. With the exception of one lesion, parlour screening was as accurate
      as the lifted foot inspection in determining the presence of 86 DD lesions on 160
      hind feet (99% agreement; kappa 0.99; sensitivity 1.00; specificity 0.99).
      Describing lesions by colour, depth or stage of lesion in the parlour or using
      the borescope reached substantial agreement with the gold standard. The stage of
      lesion was closely linked to colour and depth descriptors. There was greater
      agreement when categorising more advanced stages of disease progression.
      Borescope and parlour inspections led to both over and under recording of actual
      size, particularly in smaller lesions. Screening cows in traditional milking
      parlours for the presence of DD was found to be an accurate and practical means
      of detecting lesions. This method should be considered for on farm use to
      evaluate DD prevention and treatment strategies.

PMID- 22874894
TI  - Distribution of terrestrial gamma radiation dose rate in the eastern coastal area
      of Odisha, India.
AB  - Terrestrial gamma radiation is one of the important radiation exposures on the
      earth's surface that results from the three primordial radionuclides (226)Ra,
      (232)Th and (40)K. The elemental concentration of these elements in the earth's
      crust could result in the anomalous variation of the terrestrial gamma radiation
      in the environment. The geology of the local area plays an important role in
      distribution of these radioactive elements. Environmental terrestrial gamma
      radiation dose rates were measured around the eastern coastal area of Odisha with
      the objective of establishing baseline data on the background radiation level.
      The values of the terrestrial gamma radiation dose rate vary significantly at
      different locations in the study area. The values of the terrestrial gamma dose
      rate ranged from 77 to 1651 nGy h(-1), with an average of 230 nGy h(-1). During
      the measurement of the terrestrial gamma dose rate, sand and soil samples were
      also collected for the assessment of natural radionuclides. The activities of
      (226)Ra, (232)Th and (40)K from these samples were measured using a gamma-ray
      spectrometry with a NaI(Tl) detector. Activity concentrations of (226)Ra, (232)Th
      and (40)K ranged from 15.6 to 69 Bq kg(-1) with an average of 46.7 Bq kg(-1),
      from 28.9 to 973 Bq kg(-1) with an average of 250 Bq kg(-1) and from 139 to 952
      Bq kg(-1) with an average of 429, respectively. The detailed significance of
      these studies has been discussed from the radiation protection point of view.

PMID- 22874895
TI  - Characterisation of neutron fields at Cernavoda NPP.
AB  - Near a nuclear reactor or a fuel container, mixed neutron/gamma fields are very
      common, necessitating routine neutron dosimetry. Accurate neutron dosimetry is
      complicated by the fact that the neutron effective dose is strongly dependent on
      the neutron energy and the direction distribution of the neutron fluence. Neutron
      field characterisation is indispensable if one wants to obtain a reliable
      estimate for the neutron dose. A measurement campaign at CANDU nuclear power
      plant located in Cernavoda, Romania, was set up to characterise the neutron
      fields in four different locations and to investigate the behaviour of different
      neutron personal dosemeters. This investigation intends to assist in choosing a
      suitable neutron dosimetry system at this nuclear power plant.

PMID- 22874896
TI  - Thoron and radon measurements in Romanian schools.
AB  - A new thoron/radon survey was started in the north-western part of Romania,
      covering three counties, using discriminative detectors (RADUET). All detectors
      were deployed throughout 3 months, covering the spring period. The measured radon
      and thoron concentration ranged from 31 to 414 Bq m(-3) and from below the
      detection limit to 235 Bq m(-3), respectively. In this survey, 35 schools were
      submitted to investigation; 21 of the schools included in this study presented
      radon concentrations higher than 100 Bq m(-3), the reference level recommended by
      the World Health Organization in 2009. The seasonal effective dose calculated
      from these exposures, overlapping all three counties, ranged between 0.32 and
      0.54 mSv.

PMID- 22874897
TI  - Canadian population risk of radon induced lung cancer: a re-assessment based on
      the recent cross-Canada radon survey.
AB  - Exposure to indoor radon has been determined to be the second leading cause of
      lung cancer after tobacco smoking. Canadian population risk of radon induced lung
      cancer was assessed in 2005 with the radon distribution characteristics
      determined from a radon survey carried out in the late 1970s in 19 cities. In
      that survey, a grab sampling method was used to measure radon levels. The
      observed radon concentration in 14,000 Canadian homes surveyed followed a log
      normal distribution with a geometric mean (GM) of 11.2 Bq m(-3) and a geometric
      standard deviation (GSD) of 3.9. Based on the information from that survey, it
      was estimated that ~10 % of lung cancers in Canada resulted from indoor radon
      exposure. To gain a better understanding of radon concentrations in homes across
      the country, a national residential radon survey was launched in April 2009. In
      the recent survey, long-term (3 month or longer) indoor radon measurements were
      made in roughly 14 000 homes in 121 health regions across Canada. The observed
      radon concentrations follow, as expected, a log-normal distribution with a GM of
      41.9 Bq m(-3) and a GSD of 2.8. Based on the more accurate radon distribution
      characteristics obtained from the recent cross-Canada radon survey, a re
      assessment of Canadian population risk for radon induced lung cancer was
      undertaken. The theoretical estimates show that 16 % of lung cancer deaths among
      Canadians are attributable to indoor radon exposure. These results strongly
      suggest the ongoing need for the Canadian National Radon Program. In particular,
      there is a need for a focus on education and awareness by all levels of
      government, and in partnership with key stakeholders, to encourage Canadians to
      take action to reduce the risk from indoor radon exposure.

PMID- 22874898
TI  - Assessment of effective absorbed dose of (111)In-DTPA-Buserelin in human on the
      basis of biodistribution rat data.
AB  - In this study, the effective absorbed dose to human organs was estimated,
      following intra vascular administration of (111)In-DTPA-Buserelin using
      biodistribution data from rats. Rats were sacrificed at exact time intervals of
      0.25, 0.5, 1, 2, 4 and 24 h post injections. The Medical Internal Radiation Dose
      formulation was applied to extrapolate from rats to humans and to project the
      absorbed radiation dose for various human organs. From rat data, it was estimated
      that a 185-MBq injection of (111)In-DTPA-Buserelin into the human might result in
      an estimated absorbed dose of 24.27 mGy to the total body and the highest
      effective absorbed dose was in kidneys, 28.39 mSv. The promising results of this
      study emphasises the importance of absorbed doses in humans estimated from data
      on rats.

PMID- 22874900
TI  - Encapsulation controlled single molecule magnetism in tetrathiafulvalene-capped
      cyanide-bridged cubes.
AB  - New TTF-based (TTF = tetrathiafulvalene) ligands, L1 and L2 (L1 = alpha-(4'
      methyl-4,5-ethylenedithiotetrathiafulvalene-5'-thio)-alpha'-[tris-2,2,2-(1
      pyrazolyl)ethoxy]-p-xylene and L2 = alpha-(4'-methyl-4,5
      dimethylthiotetrathiafulvalene-5'-thio)-alpha'-[tris-2,2,2-(1-pyrazolyl)ethoxy]-p
      xylene), possessing tris-pyrazolyl coordination sites, were synthesized. The
      reactions of Ni(BF(4))(2).6H(2)O with the TTF-ligands (L1 and L2), n
      Bu(4)N[Fe(CN)(3)(tp or pztp)] (tp = hydrotris(pyrazol-1-yl)borate and pztp =
      tetrakis(pyrazol-1-yl)borate) in the presence of additional counter ions afforded
      two cyanide-bridged octanuclear complexes:
      [Fe(III)(4)Ni(II)(4)(CN)(12)(pztp)(4)(L1)(4)](BF(4))(4) (1) and
      [Fe(III)(4)Ni(II)(4)(CN)(12)(pztp)(4)(L2)(4)](PF(6))(4) (2). Using a similar
      procedure to that employed in the synthesis of complex 2, with the addition of
      sodium tetraphenylborate, yielded a two-electron-reduced compound,
      Na[Fe(III)(2)Fe(II)(2)Ni(II)(4)(CN)(12)(tp)(4)(L2)(4)](BF(4))(3) (3), in which a
      sodium ion was encapsulated by the cube. The host-guest complex 3 showed enhanced
      redox behaviour and while magnetic susceptibility measurements revealed
      ferromagnetic interactions to be operative in all three complexes, the cation
      encapsulation behaviour of 3 led it to exhibit single molecule magnet-type
      properties.

PMID- 22874899
TI  - Altered generation of induced regulatory T cells in the FVB.mdr1a-/- mouse model
      of colitis.
AB  - The FVB.mdr1a(-/-) mouse, lacking the small molecule pump P-glycoprotein (P-gp),
      is a commonly used model for the study of spontaneous T cell-mediated colitis. In
      addition, MDR1 polymorphisms and P-gp deficiency in humans have been linked to
      the development of ulcerative colitis. We now demonstrate that mice with P-gp
      deficiency have decreased levels of Foxp3(+) regulatory T cells (Tregs) in the
      intestinal lamina propria. This decrease is not due to either increased Treg
      apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become
      Foxp3(+)IL-17(+) cells. Instead, P-gp deficiency appears to restrict the
      development of induced Treg cells (iTregs), as fewer Foxp3(+) iTregs developed
      from naive FVB.mdr1a(-/-) T cells both upon transforming growth factor-beta (TGF
      beta) treatment in vitro and after adoptive transfer into FVB.rag2(-/-)
      recipients. Rather, in vitro TGF-beta treatment results in a IL-17(+)CD4(+) T
      cell. This failure of iTregs to develop explains the decrease in Foxp3(+) Tregs
      in the FVB.mdr1a(-/-) intestine, representing a need to investigate this novel
      disease mechanism in human inflammatory bowel disease patients with MDR1
      polymorphisms.

PMID- 22874907
TI  - Newborn screening of congenital cytomegalovirus infection using saliva can be
      influenced by breast feeding.

PMID- 22874909
TI  - Insights from the Israeli occupational health system.

PMID- 22874912
TI  - Epidermal and cortical roles of NFP and DMI3 in coordinating early steps of
      nodulation in Medicago truncatula.
AB  - Legumes have evolved the capacity to form a root nodule symbiosis with soil
      bacteria called rhizobia. The establishment of this symbiosis involves specific
      developmental events occurring both in the root epidermis (notably bacterial
      entry) and at a distance in the underlying root cortical cells (notably cell
      divisions leading to nodule organogenesis). The processes of bacterial entry and
      nodule organogenesis are tightly linked and both depend on rhizobial production
      of lipo-chitooligosaccharide molecules called Nod factors. However, how these
      events are coordinated remains poorly understood. Here, we have addressed the
      roles of two key symbiotic genes of Medicago truncatula, the lysin motif (LysM)
      domain-receptor like kinase gene NFP and the calcium- and calmodulin-dependent
      protein kinase gene DMI3, in the control of both nodule organogenesis and
      bacterial entry. By complementing mutant plants with corresponding genes
      expressed either in the epidermis or in the cortex, we have shown that epidermal
      DMI3, but not NFP, is sufficient for infection thread formation in root hairs.
      Epidermal NFP is sufficient to induce cortical cell divisions leading to nodule
      primordia formation, whereas DMI3 is required in both cell layers for these
      processes. Our results therefore suggest that a signal, produced in the epidermis
      under the control of NFP and DMI3, is responsible for activating DMI3 in the
      cortex to trigger nodule organogenesis. We integrate these data to propose a new
      model for epidermal/cortical crosstalk during early steps of nodulation.

PMID- 22874913
TI  - Drosophila CORL is required for Smad2-mediated activation of Ecdysone Receptor
      expression in the mushroom body.
AB  - CORL proteins (FUSSEL/SKOR proteins in humans) are related to Sno/Ski oncogenes
      but their developmental roles are unknown. We have cloned Drosophila CORL and
      show that its expression is restricted to distinct subsets of cells in the
      central nervous system. We generated a deletion of CORL and noted that homozygous
      individuals rarely survive to adulthood. Df(4)dCORL adult escapers display
      mushroom body (MB) defects and Df(4)dCORL larvae are lacking Ecdysone Receptor
      (EcR-B1) expression in MB neurons. This is phenocopied in CORL-RNAi and Smad2
      RNAi clones in wild-type larvae. Furthermore, constitutively active Baboon (type
      I receptor upstream of Smad2) cannot stimulate EcR-B1 MB expression in Df(4)dCORL
      larvae, which demonstrates a formal requirement for CORL in Smad2 signaling.
      Studies of mouse Corl1 (Skor1) revealed that it binds specifically to Smad3.
      Overall, the data suggest that CORL facilitates Smad2 activity upstream of EcR-B1
      in the MB. The conservation of neural expression and strong sequence homology of
      all CORL proteins suggests that this is a new family of Smad co-factors.

PMID- 22874914
TI  - BMP-dependent serosa and amnion specification in the scuttle fly Megaselia
      abdita.
AB  - Bone morphogenetic protein (BMP) signaling is an essential factor in dorsoventral
      patterning of animal embryos but how BMP signaling evolved with fundamental
      changes in dorsoventral tissue differentiation is unclear. Flies experienced an
      evolutionary reduction of extra-embryonic tissue types from two (amniotic and
      serosal tissue) to one (amnionserosal tissue). BMP-dependent amnioserosa
      specification has been studied in Drosophila melanogaster. However, the
      mechanisms of serosal and amniotic tissue specification in less diverged flies
      remain unknown. To better understand potential evolutionary links between BMP
      signaling and extra-embryonic tissue specification, we examined the activity
      profile and function of BMP signaling in serosa and amnion patterning of the
      scuttle fly Megaselia abdita (Phoridae) and compared the BMP activity profiles
      between M. abdita and D. melanogaster. In blastoderm embryos of both species, BMP
      activity peaked at the dorsal midline. However, at the beginning of gastrulation,
      peak BMP activity in M. abdita shifted towards prospective amnion tissue. This
      transition correlated with the first signs of amnion differentiation laterally
      adjacent to the serosa anlage. Marker-assisted analysis of six BMP signaling
      components (dpp, gbb, scw, tkv, sax, sog) by RNA interference revealed that both
      serosa and amnion specification of M. abdita are dependent on BMP activity.
      Conversely, BMP gain-of-function experiments caused sharpened expression
      boundaries of extra-embryonic target genes indicative of positive feedback. We
      propose that changes in the BMP activity profile at the beginning of gastrulation
      might have contributed to the reduction of extra-embryonic tissue types during
      the radiation of cyclorrhaphan flies.

PMID- 22874915
TI  - Formation and specification of a Drosophila dopaminergic precursor cell.
AB  - Dopaminergic neurons play important roles in animal behavior, including
      motivation, reward and locomotion. The Drosophila dopaminergic H-cell interneuron
      is an attractive system for studying the genetics of neural development because
      analysis is focused on a single neuronal cell type. Here we provide a mechanistic
      understanding of how MP3, the precursor to the H-cell, forms and acquires its
      identity. We show that the gooseberry/gooseberry-neuro (gsb/gsb-n) transcription
      factor genes act to specify MP3 cell fate. It is proposed that single-minded
      commits neuroectodermal cells to a midline fate, followed by a series of
      signaling events that result in the formation of a single gsb(+)/gsb-n(+) MP3
      cell per segment. The wingless signaling pathway establishes a midline anterior
      domain by activating expression of the forkhead transcription factors sloppy
      paired 1 and sloppy paired 2. This is followed by hedgehog signaling that
      activates gsb/gsb-n expression in a subgroup of anterior cells. Finally, Notch
      signaling results in the selection of a single MP3, with the remaining cells
      becoming midline glia. In MP3, gsb/gsb-n direct H-cell development, in large part
      by activating expression of the lethal of scute and tailup H-cell regulatory
      genes. Thus, a series of signaling and transcriptional events result in the
      specification of a unique dopaminergic precursor cell. Additional genetic
      experiments indicate that the molecular mechanisms that govern MP3/H-cell
      development might also direct the development of non-midline dopaminergic
      neurons.

PMID- 22874916
TI  - Atonal and EGFR signalling orchestrate rok- and Drak-dependent adherens junction
      remodelling during ommatidia morphogenesis.
AB  - Morphogenesis of epithelial tissues relies on the interplay between cell
      division, differentiation and regulated changes in cell shape, intercalation and
      sorting. These processes are often studied individually in relatively simple
      epithelia that lack the complexity found during organogenesis when these
      processes might all coexist simultaneously. To address this issue, we are making
      use of the developing fly retinal neuroepithelium. Retinal morphogenesis relies
      on a coordinated sequence of interdependent morphogenetic events that includes
      apical cell constriction, localized alignment of groups of cells and ommatidia
      morphogenesis coupled to neurogenesis. Here, we use live imaging to document the
      sequence of adherens junction (AJ) remodelling events required to generate the
      fly ommatidium. In this context, we demonstrate that the kinases Rok and Drak
      function redundantly during Myosin II-dependent cell constriction, subsequent
      multicellular alignment and AJ remodelling. In addition, we show that early
      multicellular patterning characterized by cell alignment is promoted by the
      conserved transcription factor Atonal (Ato). Further ommatidium patterning
      requires the epidermal growth factor receptor (EGFR) signalling pathway, which
      transcriptionally governs rok- and Drak-dependent AJ remodelling while also
      promoting neurogenesis. In conclusion, our work reveals an important role for
      Drak in regulating AJ remodelling during retinal morphogenesis. It also sheds new
      light on the interplay between Ato, EGFR-dependent transcription and AJ
      remodelling in a system in which neurogenesis is coupled with cell shape changes
      and regulated steps of cell intercalation.

PMID- 22874918
TI  - p57kip2 regulates glial fate decision in adult neural stem cells.
AB  - Our recent studies revealed p57kip2 as an intrinsic regulator of late gliogenesis
      and demonstrated that in oligodendroglial precursor cells p57kip2 inhibition
      leads to accelerated maturation. Adult neural stem cells have been described as a
      source of glial progenitors; however, the underlying mechanisms of cell fate
      specification are still poorly understood. Here, we have investigated whether
      p57kip2 can influence early events of glial determination and differentiation. We
      found that Sox2/GFAP double-positive cells express p57kip2 in stem cell niches of
      the adult brain. Short-hairpin RNA-mediated suppression of p57kip2 in cultured
      adult neural stem cells was found to strongly reduce astroglial characteristics,
      while oligodendroglial precursor features were increased. Importantly, this anti
      astrogenic effect of p57kip2 suppression dominated the bone morphogenetic protein
      mediated promotion of astroglial differentiation. Moreover, we observed that in
      p57kip2 knockdown cells, the BMP antagonist chordin was induced. Finally, when
      p57kip2-suppressed stem cells were transplanted into the adult spinal cord, fewer
      GFAP-positive cells were generated and oligodendroglial markers were induced when
      compared with control cells, demonstrating an effect of in vivo relevance.

PMID- 22874917
TI  - Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without
      causing uniform migration defects.
AB  - Neuronal precursors, generated throughout life in the subventricular zone,
      migrate through the rostral migratory stream to the olfactory bulb where they
      differentiate into interneurons. We found that the PI3K-Akt-mTorc1 pathway is
      selectively inactivated in migrating neuroblasts in the subventricular zone and
      rostral migratory stream, and activated when these cells reach the olfactory
      bulb. Postnatal deletion of Pten caused aberrant activation of the PI3K-Akt
      mTorc1 pathway and an enlarged subventricular zone and rostral migratory stream.
      This expansion was caused by premature termination of migration and
      differentiation of neuroblasts and was rescued by inhibition of mTorc1. This
      phenotype is reminiscent of lamination defects caused by Pten deletion in
      developing brain that were previously described as defective migration. However,
      live imaging in acute slices showed that Pten deletion did not cause a uniform
      defect in the mechanics of directional neuroblast migration. Instead, a
      subpopulation of Pten-null neuroblasts showed minimal movement and altered
      morphology associated with differentiation, whereas the remainder showed
      unimpeded directional migration towards the olfactory bulb. Therefore, migration
      defects of Pten-null neurons might be secondary to ectopic differentiation.

PMID- 22874920
TI  - Spatiotemporal manipulation of retinoic acid activity in zebrafish hindbrain
      development via photo-isomerization.
AB  - All-trans retinoic acid (RA) is a key player in many developmental pathways. Most
      methods used to study its effects in development involve continuous all-trans RA
      activation by incubation in a solution of all-trans RA or by implanting all-trans
      RA-soaked beads at desired locations in the embryo. Here we show that the UV
      driven photo-isomerization of 13-cis RA to the trans-isomer (and vice versa) can
      be used to non-invasively and quantitatively control the concentration of all
      trans RA in a developing embryo in time and space. This facilitates the global or
      local perturbation of developmental pathways with a pulse of all-trans RA of
      known concentration or its inactivation by UV illumination. In zebrafish embryos
      in which endogenous synthesis of all-trans RA is impaired, incubation for as
      little as 5 minutes in 1 nM all-trans RA (a pulse) or 5 nM 13-cis RA followed by
      1-minute UV illumination is sufficient to rescue the development of the hindbrain
      if performed no later than bud stage. However, if subsequent to this all-trans RA
      pulse the embryo is illuminated (no later than bud stage) for 1 minute with UV
      light (to isomerize, i.e. deactivate, all-trans RA), the rescue of hindbrain
      development is impaired. This suggests that all-trans RA is sequestered in
      embryos that have been transiently exposed to it. Using 13-cis RA isomerization
      with UV light, we further show that local illumination at bud stage of the head
      region (but not the tail) is sufficient to rescue hindbrain formation in embryos
      whose all-trans RA synthetic pathway has been impaired.

PMID- 22874919
TI  - A Sox9/Fgf feed-forward loop maintains pancreatic organ identity.
AB  - All mature pancreatic cell types arise from organ-specific multipotent progenitor
      cells. Although previous studies have identified cell-intrinsic and -extrinsic
      cues for progenitor cell expansion, it is unclear how these cues are integrated
      within the niche of the developing organ. Here, we present genetic evidence in
      mice that the transcription factor Sox9 forms the centerpiece of a gene
      regulatory network that is crucial for proper organ growth and maintenance of
      organ identity. We show that pancreatic progenitor-specific ablation of Sox9
      during early pancreas development causes pancreas-to-liver cell fate conversion.
      Sox9 deficiency results in cell-autonomous loss of the fibroblast growth factor
      receptor (Fgfr) 2b, which is required for transducing mesenchymal Fgf10 signals.
      Likewise, Fgf10 is required to maintain expression of Sox9 and Fgfr2 in
      epithelial progenitors, showing that Sox9, Fgfr2 and Fgf10 form a feed-forward
      expression loop in the early pancreatic organ niche. Mirroring Sox9 deficiency,
      perturbation of Fgfr signaling in pancreatic explants or genetic inactivation of
      Fgf10 also result in hepatic cell fate conversion. Combined with previous
      findings that Fgfr2b or Fgf10 are necessary for pancreatic progenitor cell
      proliferation, our results demonstrate that organ fate commitment and progenitor
      cell expansion are coordinately controlled by the activity of a Sox9/Fgf10/Fgfr2b
      feed-forward loop in the pancreatic niche. This self-promoting Sox9/Fgf10/Fgfr2b
      loop may regulate cell identity and organ size in a broad spectrum of
      developmental and regenerative contexts.

PMID- 22874921
TI  - Convergent repression of Foxp2 3'UTR by miR-9 and miR-132 in embryonic mouse
      neocortex: implications for radial migration of neurons.
AB  - MicroRNAs (miRNAs) are rapidly emerging as a new layer of regulation of mammalian
      brain development. However, most of the miRNA target genes remain unidentified.
      Here, we explore gene expression profiling upon miRNA depletion and in vivo
      target validation as a strategy to identify novel miRNA targets in embryonic
      mouse neocortex. By this means, we find that Foxp2, a transcription factor
      associated with speech and language development and evolution, is a novel miRNA
      target. In particular, we find that miR-9 and miR-132 are able to repress ectopic
      expression of Foxp2 protein by targeting its 3' untranslated region (3'UTR) in
      vivo. Interestingly, ectopic expression of Foxp2 in cortical projection neurons
      (a scenario that mimics the absence of miRNA-mediated silencing of Foxp2
      expression) delays neurite outgrowth in vitro and impairs their radial migration
      in embryonic mouse neocortex in vivo. Our results uncover a new layer of control
      of Foxp2 expression that may be required for proper neuronal maturation.

PMID- 22874922
TI  - Novel non-canonical TGF-beta signaling networks: emerging roles in airway smooth
      muscle phenotype and function.
AB  - The airway smooth muscle (ASM) plays an important role in the pathophysiology of
      asthma and chronic obstructive pulmonary disease (COPD). ASM cells express a wide
      range of receptors involved in contraction, growth, matrix protein production and
      the secretion of cytokines and chemokines. Transforming growth factor beta (TGF
      beta) is one of the major players in determining the structural and functional
      abnormalities of the ASM in asthma and COPD. It is increasingly evident that TGF
      beta functions as a master switch, controlling a network of intracellular and
      autocrine signaling loops that effect ASM phenotype and function. In this review,
      the various elements that participate in non-canonical TGF-beta signaling,
      including MAPK, PI3K, WNT/beta-catenin, and Ca(2+), are discussed, focusing on
      their effect on ASM phenotype and function. In addition, new aspects of ASM
      biology and their possible association with non-canonical TGF-beta signaling will
      be discussed.

PMID- 22874923
TI  - Seroepidemiological study of caprine toxoplasmosis in East and West Shewa Zones,
      Oromia Regional State, Central Ethiopia.
AB  - Toxoplasmosis is a global zoonosis caused by Toxoplasma gondii, an intracellular
      apicomplexan parasite. The objectives of this study were to estimate the animal
      and flock level seroprevalence and risk factors associated with toxoplasmosis in
      goats of Central Ethiopia. In Ethiopia, goats are economically important animals
      used for meat and milk production. The study was cross-sectional and 927 blood
      samples from 187 goat flocks were collected to examine T. gondii specific IgG
      antibodies by enzyme linked immunosorbent assay (ELISA). A questionnaire was used
      to collect data on the potential risk factors. The study revealed flock and
      animal level seroprevalence of 58.3% (109/187; 95% confidence interval [CI]:
      51.16, 65.42) and 19.7% (183/927; 95% CI: 17.17, 22.31), respectively. The
      likelihood of acquiring T. gondii infection was higher in semi-intensively
      managed goats (Odds ratio [OR]=2.48, 95% confidence interval [CI]: 1.14, 5.37;
      P=0.022) than in extensively managed goats, in females than in males (OR=1.84,
      95% CI: 1.16, 2.92; P=0.010), in adults than in young animals (OR=2.00, 95% CI:
      1.21, 3.28; P=0.006), in small than in large flocks (OR=2.03, 95% CI: 1.03, 3.98;
      P=0.040), in goats kept under sedentary (OR=2.81, 95% CI: 1.41, 5.59; P=0.003)
      and agropastoral farming system (OR=3.62, 95% CI: 1.83, 7.18; P<0.001) than
      pastoral farming system and in goats allowed to drink water from the tap than
      those drinking from river and stagnant water bodies (OR=9.25, 95% CI: 3.04,
      28.15; P<0.001). Our study indicates that exposure of goats to oocysts of T.
      gondii is widespread. We recommend further studies to determine the genotype of
      the parasite, public health and economic impacts of toxoplasmosis and the role of
      raw goat meat and milk as a source of infection for consumers.

PMID- 22874924
TI  - Anaemia in the sow: a cohort study to assess factors with an impact on
      haemoglobin concentration, and the influence of haemoglobin concentration on the
      reproductive performance.
AB  - The aim of this study was to conduct a descriptive study of haemoglobin
      concentration found on high-prolificacy sows, to study the relationship between
      the concentration of haemoglobin and body reserves, and to determine whether
      anaemia is a risk factor for reproductive performance. A cohort of 308 sows from
      seven farms was followed from the last third of gestation to the confirmation of
      the following gestation. Haemoglobin concentration was assessed at four stages of
      the reproductive cycle: seven and four weeks before farrowing, a few days and
      three weeks after farrowing. Backfat thickness (BFT) was measured at parturition.
      The results were analysed using linear mixed-effect models. The mean haemoglobin
      concentration was 108.4 g/l. The mean modellised haemoglobin concentration of
      parity 1 sows with a BFT of 16 mm, sampled seven weeks before farrowing, was 118
      g/l. Haemoglobin concentration of sows of parity 6 or higher was 8.0 g/l lower
      than those of parity 1 sows (95% confidence interval -11.0 to -5.1). Haemoglobin
      concentration is lower in sows with a lower BFT, whatever parity rank. There is
      no evidence of a relation between haemoglobin concentration and the number of
      total born, stillborn or number of piglets alive at three weeks and the next
      breeding performance.

PMID- 22874925
TI  - In vivo antioxidant activity of total flavonoids from indocalamus leaves in aging
      mice caused by D-galactose.
AB  - OBJECTIVE: The aim of this thesis is to explore antioxidant activity of total
      flavonoids extracted from indocalamus leaves. METHOD: Aging mice model was
      established by D-galactose induction. Three groups of mice were treated with
      total flavonoids extracted from indocalamus leaves at doses of 20, 40 and 80
      mg/kg d bw respectively. The antioxidant status in the aging mice was measured by
      determining the activities of superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px), catalase (CAT) and total anti-oxidant capability (T-AOC) in the serum
      and liver and malondialdehyde (MDA) content in the serum, liver and brain.
      RESULTS: Compared with control group, extracts of indocalamus leaves
      significantly enhanced activities of SOD, GSH-Px, CAT in the serum and liver, and
      decreased MDA content in the serum, liver and brain at the tested doses.
      CONCLUSION: Total flavonoids extracted from indocalamus leaves demonstrated the
      potent antioxidant activity.

PMID- 22874926
TI  - Take a look.

PMID- 22874927
TI  - Who calls the shots?

PMID- 22874928
TI  - Arab liberals must stay in the game.

PMID- 22874940
TI  - Mars rover sizes up the field.

PMID- 22874941
TI  - Stem-cell pioneer banks on future therapies.

PMID- 22874942
TI  - Britain's big bet on graphene.

PMID- 22874943
TI  - Heatwaves blamed on global warming.

PMID- 22874945
TI  - Extreme mechanics: Buckling down.

PMID- 22874944
TI  - Physics prize dwarfs all others.

PMID- 22874946
TI  - Cancer research: Open ambition.

PMID- 22874947
TI  - Science journalism: Let's talk about sex.

PMID- 22874951
TI  - Romania: Misconduct rule is not retroactive.

PMID- 22874952
TI  - Science for the masses: Time for a Higgs metaphor upgrade.

PMID- 22874953
TI  - Alzheimer's: Put patients and researchers in touch.

PMID- 22874954
TI  - Performance enhancement: To embrace doping in sport is absurd.

PMID- 22874955
TI  - Publishing: Alarming shift away from sharing results.

PMID- 22874956
TI  - Astrobiology: Frontier or fiction.

PMID- 22874957
TI  - Palaeoanthropology: Facing up to complexity.

PMID- 22874958
TI  - Optics: Gain and loss mixed in the same cauldron.

PMID- 22874960
TI  - Atmospheric chemistry: The X factor.

PMID- 22874961
TI  - Structural biology: Dynamic binding.

PMID- 22874962
TI  - Parity-time synthetic photonic lattices.
AB  - The development of new artificial structures and materials is today one of the
      major research challenges in optics. In most studies so far, the design of such
      structures has been based on the judicious manipulation of their refractive index
      properties. Recently, the prospect of simultaneously using gain and loss was
      suggested as a new way of achieving optical behaviour that is at present
      unattainable with standard arrangements. What facilitated these quests is the
      recently developed notion of 'parity-time symmetry' in optical systems, which
      allows a controlled interplay between gain and loss. Here we report the
      experimental observation of light transport in large-scale temporal lattices that
      are parity-time symmetric. In addition, we demonstrate that periodic structures
      respecting this symmetry can act as unidirectional invisible media when operated
      near their exceptional points. Our experimental results represent a step in the
      application of concepts from parity-time symmetry to a new generation of
      multifunctional optical devices and networks.

PMID- 22874963
TI  - Quantum teleportation and entanglement distribution over 100-kilometre free-space
      channels.
AB  - Transferring an unknown quantum state over arbitrary distances is essential for
      large-scale quantum communication and distributed quantum networks. It can be
      achieved with the help of long-distance quantum teleportation and entanglement
      distribution. The latter is also important for fundamental tests of the laws of
      quantum mechanics. Although quantum teleportation and entanglement distribution
      over moderate distances have been realized using optical fibre links, the huge
      photon loss and decoherence in fibres necessitate the use of quantum repeaters
      for larger distances. However, the practical realization of quantum repeaters
      remains experimentally challenging. Free-space channels, first used for quantum
      key distribution, offer a more promising approach because photon loss and
      decoherence are almost negligible in the atmosphere. Furthermore, by using
      satellites, ultra-long-distance quantum communication and tests of quantum
      foundations could be achieved on a global scale. Previous experiments have
      achieved free-space distribution of entangled photon pairs over distances of 600
      metres (ref. 14) and 13 kilometres (ref. 15), and transfer of triggered single
      photons over a 144-kilometre one-link free-space channel. Most recently,
      following a modified scheme, free-space quantum teleportation over 16 kilometres
      was demonstrated with a single pair of entangled photons. Here we report quantum
      teleportation of independent qubits over a 97-kilometre one-link free-space
      channel with multi-photon entanglement. An average fidelity of 80.4 +/- 0.9 per
      cent is achieved for six distinct states. Furthermore, we demonstrate
      entanglement distribution over a two-link channel, in which the entangled photons
      are separated by 101.8 kilometres. Violation of the Clauser-Horne-Shimony-Holt
      inequality is observed without the locality loophole. Besides being of
      fundamental interest, our results represent an important step towards a global
      quantum network. Moreover, the high-frequency and high-accuracy acquiring,
      pointing and tracking technique developed in our experiment can be directly used
      for future satellite-based quantum communication and large-scale tests of quantum
      foundations.

PMID- 22874964
TI  - A new atmospherically relevant oxidant of sulphur dioxide.
AB  - Atmospheric oxidation is a key phenomenon that connects atmospheric chemistry
      with globally challenging environmental issues, such as climate change,
      stratospheric ozone loss, acidification of soils and water, and health effects of
      air quality. Ozone, the hydroxyl radical and the nitrate radical are generally
      considered to be the dominant oxidants that initiate the removal of trace gases,
      including pollutants, from the atmosphere. Here we present atmospheric
      observations from a boreal forest region in Finland, supported by laboratory
      experiments and theoretical considerations, that allow us to identify another
      compound, probably a stabilized Criegee intermediate (a carbonyl oxide with two
      free-radical sites) or its derivative, which has a significant capacity to
      oxidize sulphur dioxide and potentially other trace gases. This compound probably
      enhances the reactivity of the atmosphere, particularly with regard to the
      production of sulphuric acid, and consequently atmospheric aerosol formation. Our
      findings suggest that this new atmospherically relevant oxidation route is
      important relative to oxidation by the hydroxyl radical, at least at moderate
      concentrations of that radical. We also find that the oxidation chemistry of this
      compound seems to be tightly linked to the presence of alkenes of biogenic
      origin.

PMID- 22874965
TI  - Water balance of global aquifers revealed by groundwater footprint.
AB  - Groundwater is a life-sustaining resource that supplies water to billions of
      people, plays a central part in irrigated agriculture and influences the health
      of many ecosystems. Most assessments of global water resources have focused on
      surface water, but unsustainable depletion of groundwater has recently been
      documented on both regional and global scales. It remains unclear how the rate of
      global groundwater depletion compares to the rate of natural renewal and the
      supply needed to support ecosystems. Here we define the groundwater footprint
      (the area required to sustain groundwater use and groundwater-dependent ecosystem
      services) and show that humans are overexploiting groundwater in many large
      aquifers that are critical to agriculture, especially in Asia and North America.
      We estimate that the size of the global groundwater footprint is currently about
      3.5 times the actual area of aquifers and that about 1.7 billion people live in
      areas where groundwater resources and/or groundwater-dependent ecosystems are
      under threat. That said, 80 per cent of aquifers have a groundwater footprint
      that is less than their area, meaning that the net global value is driven by a
      few heavily overexploited aquifers. The groundwater footprint is the first tool
      suitable for consistently evaluating the use, renewal and ecosystem requirements
      of groundwater at an aquifer scale. It can be combined with the water footprint
      and virtual water calculations, and be used to assess the potential for
      increasing agricultural yields with renewable groundwaterref. The method could be
      modified to evaluate other resources with renewal rates that are slow and
      spatially heterogeneous, such as fisheries, forestry or soil.

PMID- 22874966
TI  - New fossils from Koobi Fora in northern Kenya confirm taxonomic diversity in
      early Homo.
AB  - Since its discovery in 1972 (ref. 1), the cranium KNM-ER 1470 has been at the
      centre of the debate over the number of species of early Homo present in the
      early Pleistocene epoch of eastern Africa. KNM-ER 1470 stands out among other
      specimens attributed to early Homo because of its larger size, and its flat and
      subnasally orthognathic face with anteriorly placed maxillary zygomatic roots.
      This singular morphology and the incomplete preservation of the fossil have led
      to different views as to whether KNM-ER 1470 can be accommodated within a single
      species of early Homo that is highly variable because of sexual, geographical and
      temporal factors, or whether it provides evidence of species diversity marked by
      differences in cranial size and facial or masticatory adaptation. Here we report
      on three newly discovered fossils, aged between 1.78 and 1.95 million years (Myr)
      old, that clarify the anatomy and taxonomic status of KNM-ER 1470. KNM-ER 62000,
      a well-preserved face of a late juvenile hominin, closely resembles KNM-ER 1470
      but is notably smaller. It preserves previously unknown morphology, including
      moderately sized, mesiodistally long postcanine teeth. The nearly complete
      mandible KNM-ER 60000 and mandibular fragment KNM-ER 62003 have a dental arcade
      that is short anteroposteriorly and flat across the front, with small incisors;
      these features are consistent with the arcade morphology of KNM-ER 1470 and KNM
      ER 62000. The new fossils confirm the presence of two contemporary species of
      early Homo, in addition to Homo erectus, in the early Pleistocene of eastern
      Africa.

PMID- 22874968
TI  - Fabrication of micro free-flow electrophoresis chip by photocurable monomer
      binding microfabrication technique for continuous separation of proteins and
      their numerical simulation.
AB  - In this study, a simple, fast, and reliable method to fabricate a micro free-flow
      electrophoresis (MUFFE) device on glass is presented. The two-dimensional depth
      channel in the chip was easily achieved by using a photocurable monomer (NOA 81)
      that served as the bonding material. In such a geometrical structure (two
      dimensional depth channel), the effect of fluid behavior on the separation
      efficiency of micro free-flow zone electrophoresis (MUFFZE) was simulated. The
      results of numerical simulation indicate that the pressure at the inlets may play
      an important role in the separation performance. Under the optimum separation
      conditions, four FITC-labeled amino acids were well separated, indicating the
      validity of the performance of the chip. Since the chip was fabricated by organic
      polymer bonding, it was easily recyclable through a simple re-fabrication
      process. The reproducibility of results from these recycling re-fabrication chips
      was investigated. The RSD of the resolution between FITC-L-glycine and FITC-L
      phenylalanine was 5.3%. Furthermore, three FITC-labeled proteins were
      successfully separated with the resolution of 2.2 and 5.46, respectively, by
      using the coating of neutral liposome.

PMID- 22874970
TI  - GOx signaling triggered by aptamer-based ATP detection.
AB  - Aptamer based ATP binding leads to the release of the co-factor FAD, which acts
      as a trigger to 'turn-on' the activity of apo-GOx and thus generates a measurable
      response.

PMID- 22874972
TI  - Evaluation of preference for voice prosthesis.

PMID- 22874973
TI  - Bipolar magnetic semiconductors: a new class of spintronics materials.
AB  - Electrical control of spin polarization is very desirable in spintronics, since
      electric fields can be easily applied locally, in contrast to magnetic fields.
      Here, we propose a new concept of bipolar magnetic semiconductors (BMS) in which
      completely spin-polarized currents with reversible spin polarization can be
      created and controlled simply by applying a gate voltage. This is a result of the
      unique electronic structure of BMS, where the valence and conduction bands
      possess opposite spin polarization when approaching the Fermi level. BMS is thus
      expected to have potential for various applications. Our band structure and spin
      polarized electronic transport calculations on semi-hydrogenated single-walled
      carbon nanotubes confirm the existence of BMS materials and demonstrate the
      electrical control of spin-polarization in them.

PMID- 22874974
TI  - Significant effect of spin flip on the oxygen atom transfer reaction from
      (oxo)manganese(V) corroles to thioanisole: insights from density functional
      calculations.
AB  - The electronic and structural features of (oxo)manganese(V) corroles and their
      catalyzed oxygen atom transfers to thioanisole in different spin states have been
      investigated by the B3LYP functional calculations. Calculations show that these
      corrole-based oxidants and their complexes with thioanisole generally have the
      singlet ground state, and their triplet forms are also accessible in
      consideration of the spin-orbit coupling interaction. Due to strong d-pi
      conjugation interactions between Mn and the corrole ring arising from the pi
      electron donation of the corrole moiety, the five-coordinated Mn approximately
      has the stable 18-electron configuration. The predicted free energy barriers for
      the singlet oxygen atom transfer reactions are generally larger than 22 kcal mol(
      1), while the spin flip in reaction may remarkably increase the reactivity. In
      particular, the bromination on beta-pyrrole carbon atoms of the meso-substituted
      (oxo)manganese(V) corrole strikingly enhances the spin-orbit coupling interaction
      and results in the dramatic increase of reactivity. The multiple spin changes are
      predicted to be involved in the low-energy reaction pathway. The present results
      show good agreement with the experimental observation and provide a detailed
      picture for the oxygen atom transfer reaction induced by the (oxo)manganese(V)
      corroles.

PMID- 22874975
TI  - Childhood obstructive sleep apnea syndrome: an interdisciplinary approach: a
      prospective epidemiological study of 4,318 five-and-a-half-year-old children.
AB  - Population-representative data on sleep disorders in children is scarce.
      BACKGROUND AND OBJECTIVE: The aim of this epidemiological study was to determine
      the prevalence of various sleep-related breathing disorders (SRBD) and any
      correlations with occlusion and jaw abnormalities in preschool children.
      MATERIALS AND METHODS: The study material consisted of 4,318 children (5.5 years
      old) whose parents completed the Pediatric Sleep Questionnaire (PSQ); 60 out of
      140 children (6.3 +/- 0.78 years old) with a positive questionnaire score (>
      0.33) were examined by an orthodontist and ENT specialist. From this cohort, 15
      children who presented a dental occlusion and jaw abnormality but no indication
      for surgical reduction of adenotonsillar tissue underwent polysomnography in a
      sleep laboratory. RESULTS: According to the PSQ, 3.3% of the 5.5-year-olds showed
      evidence of a SRBD. Boys were affected significantly more frequently. Lack of
      concentration, hyperactivity, morning fatigue, mouth breathing, loud snoring, and
      breathing interruptions were indicators of SRBD. The SRBD children more
      frequently presented with jaw abnormalities such as mandibular retrognathia,
      lateral cross-bite, and increased overjet. The SRBD cohort showed a higher rate
      of orofacial dysfunctions. Adenotonsillar hyperplasia still played a significant
      role in the development of SRBD. CONCLUSION: In contrast to previous reports in
      the literature, the frequency of SRBD in our group of 5- to 6-year-olds was lower
      (3%). Boys with adenotonsillar hyperplasia and/or mandibular retrognathia,
      lateral cross bite, and an enlarged overjet require special attention.

PMID- 22874976
TI  - fMRI: a tree with fuzzy roots.

PMID- 22874977
TI  - The author file: Oliver Brustle.

PMID- 22874978
TI  - Points of view: Managing deep data in genome browsers.

PMID- 22874979
TI  - Model organisms: Drosophila's outdoor schedule.

PMID- 22874980
TI  - Cell biology: Refined siRNA screens.

PMID- 22874981
TI  - Synthetic biology: Understudies of DNA and RNA.

PMID- 22874982
TI  - Molecular biology: Capturing sequences for bioprospecting.

PMID- 22874991
TI  - Nanobiotechnology: Controlling biology by radio.

PMID- 22874992
TI  - Improving gene-editing nucleases.

PMID- 22874993
TI  - Sequencing: Probing epigenetic cross-talk.

PMID- 22874998
TI  - PPARgamma isoforms differentially regulate metabolic networks to mediate mouse
      prostatic epithelial differentiation.
AB  - Recent observations indicate prostatic diseases are comorbidities of systemic
      metabolic dysfunction. These discoveries revealed fundamental questions regarding
      the nature of prostate metabolism. We previously showed that prostate-specific
      ablation of PPARgamma in mice resulted in tumorigenesis and active autophagy.
      Here, we demonstrate control of overlapping and distinct aspects of prostate
      epithelial metabolism by ectopic expression of individual PPARgamma isoforms in
      PPARgamma knockout prostate epithelial cells. Expression and activation of either
      PPARgamma 1 or 2 reduced de novo lipogenesis and oxidative stress and mediated a
      switch from glucose to fatty acid oxidation through regulation of genes including
      Pdk4, Fabp4, Lpl, Acot1 and Cd36. Differential effects of PPARgamma isoforms
      included decreased basal cell differentiation, Scd1 expression and triglyceride
      fatty acid desaturation and increased tumorigenicity by PPARgamma1. In contrast,
      PPARgamma2 expression significantly increased basal cell differentiation, Scd1
      expression and AR expression and responsiveness. Finally, in confirmation of in
      vitro data, a PPARgamma agonist versus high-fat diet (HFD) regimen in vivo
      confirmed that PPARgamma agonization increased prostatic differentiation markers,
      whereas HFD downregulated PPARgamma-regulated genes and decreased prostate
      differentiation. These data provide a rationale for pursuing a fundamental
      metabolic understanding of changes to glucose and fatty acid metabolism in benign
      and malignant prostatic diseases associated with systemic metabolic stress.

PMID- 22874999
TI  - Anti-apoptotic gene Bcl2 is required for stapes development and hearing.
AB  - In this paper we describe novel and specific roles for the apoptotic regulators
      Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim
      is pro-apoptotic. Characterization of the auditory systems of mice deficient for
      these molecules revealed that Bcl2-/- mice suffered severe hearing loss. This was
      conductive in nature and did not affect sensory cells of the inner ear, with
      cochlear hair cells and neurons present and functional. Bcl2-/- mice were found
      to have a malformed, often monocrural, porous stapes (the small stirrup-shaped
      bone of the middle ear), but a normally shaped malleus and incus. The deformed
      stapes was discontinuous with the incus and sometimes fused to the temporal
      bones. The defect was completely rescued in Bcl2-/-Bim-/- mice and partially
      rescued in Bcl2-/-Bim+/- mice, which displayed high-frequency hearing loss and
      thickening of the stapes anterior crus. The Bcl2-/- defect arose in utero before
      or during the cartilage stage of stapes development. These results implicate Bcl2
      and Bim in regulating survival of second pharyngeal arch or neural crest cells
      that give rise to the stapes during embryonic development.

PMID- 22875000
TI  - Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and
      functional recovery after spinal cord injury.
AB  - The role of T lymphocytes in central nervous system (CNS) injuries is
      controversial, with inconsistent results reported concerning the effects of T
      lymphocyte transfer on spinal cord injury (SCI). Here, we demonstrate that a
      specific T-lymphocyte subset enhances functional recovery after contusion SCI in
      mice. Intraperitoneal adoptive transfer of type 1 helper T (Th1)-conditioned
      cells 4 days after SCI promoted recovery of locomotor activity and tactile
      sensation and concomitantly induced regrowth of corticospinal tract and
      serotonergic fibers. However, neither type 2 helper T (Th2)- nor IL-17-producing
      helper T (Th17)-conditioned cells had such effects. Activation of microglia and
      macrophages were observed in the spinal cords of Th1-transfered mice after SCI.
      Specifically, M2 subtype of microglia/macrophages was upregulated after Th1 cell
      transfer. Neutralization of interleukin 10 secreted by Th1-conditioned cells
      significantly attenuated the beneficial effects by Th1-conditioned lymphocytes
      after SCI. We also found that Th1-conditioned lymphocytes secreted significantly
      higher levels of neurotrophic factor, neurotrophin 3 (NT-3), than Th2- or Th17
      conditioned cells. Thus, adoptive transfer of pro-inflammatory Th1-conditioned
      cells has neuroprotective effects after SCI, with prospective implications in
      immunomodulatory treatment of CNS injury.

PMID- 22875001
TI  - Rapid engraftment of human ALL in NOD/SCID mice involves deficient apoptosis
      signaling.
AB  - Previously, we found that rapid leukemia engraftment (short time to leukemia,
      TTL(short)) in the NOD/SCID/huALL (non-obese diabetic/severe combined immuno
      deficiency/human acute lymphoblastic leukemia) xenograft model is indicative of
      early patient relapse. As earlier intact apoptosis sensitivity was predictive for
      good prognosis in patients, we investigated the importance of apoptosis signaling
      on NOD/SCID/huALL engraftment. Intact apoptosome function as reflected by
      cytochrome c-related activation of caspase-3 (CRAC-positivity) was strongly
      associated with prolonged NOD/SCID engraftment (long time to leukemia, TTL(long))
      of primary leukemia cells, good treatment response and superior patient survival.
      Conversely, deficient apoptosome function (CRAC-negativity) was associated with
      rapid engraftment (TTL(short)) and early relapse. Moreover, an intact apoptosis
      signaling was associated with high transcript and protein levels of the pro
      apoptotic death-associated protein kinase1 (DAPK1). Our data strongly emphasize
      the impact of intrinsic apoptosis sensitivity of ALL cells on the engraftment
      phenotype in the NOD/SCID/huALL model, and most importantly also on patient
      outcome.

PMID- 22875002
TI  - Cre transgene results in global attenuation of the cAMP/PKA pathway.
AB  - Use of the cre transgene in in vivo mouse models to delete a specific 'floxed'
      allele is a well-accepted method for studying the effects of spatially or
      temporarily regulated genes. During the course of our investigation into the
      effect of cyclic adenosine 3',5'-monophosphate-dependent protein kinase A (PKA)
      expression on cell death, we found that cre expression either in cultured cell
      lines or in transgenic mice results in global changes in PKA target
      phosphorylation. This consequently alters gene expression profile and changes in
      cytokine secretion such as IL-6. These effects are dependent on its recombinase
      activity and can be attributed to the upregulation of specific inhibitors of PKA
      (PKI). These results may explain the cytotoxicity often associated with cre
      expression in many transgenic animals and may also explain many of the phenotypes
      observed in the context of Cre-mediated gene deletion. Our results may therefore
      influence the interpretation of data generated using the conventional cre
      transgenic system.

PMID- 22875003
TI  - Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes
      resistance mediated by Mcl-1, Bfl-1, or Bcl-B.
AB  - The novel anticancer drug ABT-737 is a Bcl-2 Homology 3 (BH3)-mimetic that
      induces apoptosis by inhibiting pro-survival Bcl-2 proteins. ABT-737 binds with
      equal affinity to Bcl-2, Bcl-xL and Bcl-w in vitro and is expected to overrule
      apoptosis resistance mediated by these Bcl-2 proteins in equal measure. We have
      profiled ABT-737 specificity for all six pro-survival Bcl-2 proteins, in p53 wild
      type or p53-mutant human T-leukemic cells. Bcl-B was untargeted, like Bfl-1 and
      Mcl-1, in accord with their low affinity for ABT-737 in vitro. However, Bcl-2
      proved a better ABT-737 target than Bcl-xL and Bcl-w. This was reflected in
      differential apoptosis-sensitivity to ABT-737 alone, or combined with etoposide.
      ABT-737 was not equally effective in displacing BH3-only proteins or Bax from Bcl
      2, as compared with Bcl-xL or Bcl-w, offering an explanation for the differential
      ABT-737 sensitivity of tumor cells overexpressing these proteins. Inducible
      expression demonstrated that BH3-only proteins Noxa, but not Bim, Puma or
      truncated Bid could overrule ABT-737 resistance conferred by Bcl-B, Bfl-1 or Mcl
      1. These data identify Bcl-B, Bfl-1 and Mcl-1, but also Bcl-xL and Bcl-w as
      potential mediators of ABT-737 resistance and indicate that target proteins can
      be differentially sensitive to BH3-mimetics, depending on the pro-apoptotic Bcl-2
      proteins they are complexed with.

PMID- 22875005
TI  - Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic
      relocalization of eEF1A by the HIV-1 Nef protein.

PMID- 22875004
TI  - Bax inhibitor-1 is a novel IP3 receptor-interacting and -sensitizing protein.

PMID- 22875006
TI  - MS-275 sensitizes osteosarcoma cells to Fas ligand-induced cell death by
      increasing the localization of Fas in membrane lipid rafts.
AB  - Fas expression is inversely correlated with the metastatic potential of
      osteosarcoma (OS) cells to the lungs. Fas+ cells are rapidly eliminated when they
      enter the lungs via their interaction with constitutive Fas ligand (FasL) on the
      lung epithelium, whereas Fas- OS cells escape this FasL-induced apoptosis and
      survive in the lung microenvironment. Upregulation of Fas expression in
      established OS lung metastases results in tumor regression. Here, we demonstrate
      that treatment of Fas- OS cells with the histone deacetylase inhibitor MS-275
      results in the upregulation of Fas mRNA and sensitizes these cells to FasL
      induced apoptosis. However, flow cytometry analysis revealed that Fas cell
      surface protein expression was not significantly increased. Rather, we observed
      increased levels of Fas within the membrane lipid rafts, as demonstrated by an
      increase in Fas expression in detergent-insoluble lipid raft fractions and
      colocalization with GM1+ lipid rafts. We had previously shown that MS-275
      treatment inhibited expression of the anti-apoptotic cellular FLICE-inhibitory
      protein (c-FLIP). Here, we demonstrated that transfection of cells with short
      hairpin RNA to c-FLIP also resulted in the localization of Fas to lipid rafts.
      Overall, our studies indicate that MS-275 sensitizes OS cells to FasL by
      upregulating the expression of Fas in membrane lipid rafts, which correlates with
      the c-FLIP-dependent distribution of Fas to lipid rafts.

PMID- 22875007
TI  - Dream content in RBD: effect of clonazepam.

PMID- 22875008
TI  - Does subjective sleep affect cognitive function in healthy elderly subjects? The
      Proof cohort.
AB  - OBJECTIVE: Some epidemiological data are available on the association between
      sleep duration and sleep quality, sleep complaints, and the aging related
      cognitive impairment in the elderly. In this study we examined a large sample of
      healthy elderly subjects to assess the relationship between sleep quality,
      subjective cognitive complaints, and neuropsychological performance. METHODS: A
      total of 272 elderly subjects (mean age 74.8 +/- 1.1 years) were recruited from a
      population-based cross-sectional study on aging and cardiovascular morbidity. All
      subjects filled in self-assessment questionnaires evaluating cognitive function,
      anxiety, depression, sleep-related parameters, and the Pittsburgh Sleep Quality
      Index (PSQI). Ambulatory polygraphy and extensive neuropsychological tests were
      also performed. Based on the total PSQI score, subjects were classified as good
      sleepers (GS, PSQI<5, n=116) and poor sleepers (PS, PSQI>=5, n=156). RESULTS:
      Poor sleep did not affect the subjective cognitive function score, subjective
      cognitive impairment being mainly related to anxiety, depression, and sleep
      medication intake. No significant differences were seen between GS and PS in any
      of the objective cognitive function tests except for the Trail Making Test A (TMA
      A), processing speed being longer in the PS group (p<0.001). Neither the presence
      of sleep-related breathing disorders nor gender affected cognitive performance.
      CONCLUSIONS: Our results suggest that in healthy elderly subjects, subjective
      sleep quality and duration did not significantly affect subjective and objective
      cognitive performances, except the attention level, for that the interference of
      sleep medication should be considered.

PMID- 22875009
TI  - Solution structure of S-DNA formed by covalent base pairing involving a disulfide
      bond.
AB  - Here, we present the solution structure of a DNA duplex containing a disulfide
      base pair (S-DNA). The unnatural nucleoside "S" possessing a thiophenyl group as
      base was incorporated into a self-complementary singled-stranded oligonucleotide.
      Crosslinking of the disulfide base pair was analyzed by non-denaturing
      polyacrylamide gel electrophoresis. Under oxidizing conditions a high molecular
      weight band as 18 mer, corresponding to the double-stranded molecule (5'
      GCGASTCGC: 3'-CGCTSAGCG), was found, whereas single-stranded self-complementary 9
      mer oligonucleotide GCGASTCGC was detected in the presence of a reducing agent.
      These results suggest that the oligonucleotide is covalently linked by disulfide
      bonding under oxidizing conditions, which can be reversibly reduced to two thiol
      groups under reducing conditions. CD spectrum of S-DNA (CGASTCG) under oxidizing
      conditions suggested that the duplex had a right-handed double-stranded structure
      similar to that of natural DNA (B-form, CGATCG). NMR studies confirmed that this
      CGASTCG resembled natural B-DNA and that the two phenyl rings derived from the
      disulfide base pairing intercalated into the duplex. However, these two phenyl
      rings were not positioned in the same plane as the other base pairs.
      Specifically, NOEs suggest that although CGASTCG adopts a structure similar to B
      type DNA, the S-DNA duplex is bent at the point of disulfide base pairing to face
      the major groove.

PMID- 22875010
TI  - Antibiotics as first-line therapy for acute appendicitis: evidence for a change
      in clinical practice.

PMID- 22875011
TI  - Lab-on-a-Chip device with laser-patterned polymer electrodes for high voltage
      application and contactless conductivity detection.
AB  - A laser-patterned microchip electrophoresis device with integrated polymer
      electrodes for DC high voltages and AC capacitively-coupled contactless
      conductivity detection was developed. Electrophoresis separations comparable to
      devices with metal electrodes were obtained, at approximately 20 times lower
      cost.

PMID- 22875012
TI  - The genetics and neuropathology of neurodegenerative disorders: perspectives and
      implications for research and clinical practice.

PMID- 22875013
TI  - Measurement of teicoplanin by liquid chromatography-tandem mass spectrometry:
      development of a novel method.
AB  - BACKGROUND: Teicoplanin is an antibiotic used for the treatment of endocarditis,
      osteomyelitis, septic arthritis and methicillin-resistant Staphylococcus aureus.
      Teicoplanin is emerging as a suitable alternative antibiotic to vancomycin, where
      their trough serum levels are monitored by immunoassay routinely. This is the
      first report detailing the development of a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for measuring teicoplanin in patients' serum.
      METHODS: An AcquityTM UPLC (ultra-pressure liquid chromatography) tandem mass
      spectrometer was used to measure teicoplanin concentrations in samples from
      patients, quality assurance schemes and quality control preparations. Ristocetin
      was successfully implemented as a suitable internal standard. Ion suppression,
      linearity, stability, matrix effects, recovery, imprecision, lower limits of
      quantification and detection, interference and method comparison against
      immunoassay were all assessed. RESULTS: Teicoplanin and ristocetin had elution
      times of 1.39 and 1.24 min, respectively. Ion suppression was shown to be
      negligible, and linear calibration curves (0-200 MUg/mL) were consistently
      reproduced to have r(2) values >0.99. Postextraction stability was achieved up to
      20 h, while matrix effects were minimal coupled with sample recovery of >93%. The
      lower limit of quantification was 1 MUg/mL, and 0.2 MUg/mL was the lower limit of
      detection. Interference with other antibiotics was dependent on the combination
      of drugs present in patients' serum. A method comparison between immunoassay and
      LC-MS/MS suggested a negative bias for tandem mass spectrometry. CONCLUSIONS:
      This novel method of teicoplanin determination by LC-MS/MS is proven to be a
      robust protocol that is consistent and reproducible. Clinicians searching for
      alternatives in therapeutic drug monitoring may have an additional option that is
      potentially more accurate and specific.

PMID- 22875014
TI  - Evaluation of haemolysis in emergency department samples requesting high
      sensitivity troponin T measurement.

PMID- 22875015
TI  - Contingency, employment intentions, and retention of vulnerable low-wage workers:
      an examination of nursing assistants in nursing homes.
AB  - PURPOSE OF THE STUDY: While theories of job turnover generally assume a strong
      correlation between job satisfaction, intention, and retention, such models may
      be limited in explaining turnover of low-wage health care workers. Low-wage
      workers likely have a lower ability to act on their employment intentions or
      plans due to a lack of resources that serve to cushion higher wage workers. In
      this study, we examine the relationship between job satisfaction, intention, and
      retention of nursing assistants in nursing homes and the role that "contingency
      factors" play in employment intentions and retention. We conceptualize
      "contingency factors" as resource-related constraints (e.g., being a single
      mother) that likely influence employment trajectories of individuals but can be
      independent of job satisfaction or intent. DESIGN AND METHODS: We use survey data
      from 315 nursing assistants in 18 nursing homes in a U.S. southern state to model
      employment intentions and retention. RESULTS: We find that job satisfaction and
      other perceived job characteristics (e.g., workload and perceived quality of
      care) are significant predictors of an individual's intent to stay in their job,
      the occupation of nursing assistant, and the field of long-term care. However, we
      find that job satisfaction and employment intentions are not significant
      predictors of retention. Instead, "contingency factors" such as being a primary
      breadwinner and individual characteristics (e.g., tenure and past health care
      experience) appear to be stronger factors in the retention of nursing assistants.
      IMPLICATIONS: Our findings have implications for understanding turnover among low
      wage health care workers and the use of proxies such as employment intentions in
      measuring turnover.

PMID- 22875016
TI  - The role of violated caregiver preferences in psychological well-being when older
      mothers need assistance.
AB  - PURPOSE: Theory and research suggest that congruence between individuals'
      preferences for future care and the patterns of care received will affect well
      being. In this article, we explore whether older mothers' psychological well
      being was affected by the children they preferred as future caregivers and
      provide assistance at a later point when the mothers experience illness or
      injury. DESIGN AND METHODS: In this article, we use a combination of quantitative
      and qualitative data collected from 234 older mothers at two points 7 years
      apart, beginning when the mothers were 65-75 years of age. RESULTS: Multivariate
      analyses demonstrated that mothers who received assistance from children whom the
      mothers did not identify as their preferred future caregivers reported higher
      depressive symptoms at the second wave; receiving care from children identified
      as preferred caregivers did not affect well-being. Qualitative data suggested
      that these patterns occurred because the "alternate" caregivers did not possess
      the socioemotional attributes of preferred children. IMPLICATIONS: These findings
      contribute to a growing body of research demonstrating the consequences of
      violated preferences, particularly when individuals are in need of support in
      later life.

PMID- 22875017
TI  - Tumour suppressors: At the SHARP end of metastasis.

PMID- 22875018
TI  - Genomics: Viral vista.

PMID- 22875019
TI  - Metastasis: No sympathy?

PMID- 22875021
TI  - Glioblastoma: Transforming fusions induce aneuploidy.

PMID- 22875020
TI  - MicroRNAs: Lines of communication.

PMID- 22875023
TI  - Hedgehog signaling is a novel therapeutic target in tamoxifen-resistant breast
      cancer aberrantly activated by PI3K/AKT pathway.
AB  - Endocrine resistance is a major challenge in the management of estrogen receptor
      (ER)-positive breast cancers. Although multiple mechanisms leading to endocrine
      resistance have been proposed, the poor outcome of patients developing resistance
      to endocrine therapy warrants additional studies. Here we show that noncanonical
      Hedgehog (Hh) signaling is an alternative growth promoting mechanism that is
      activated in tamoxifen-resistant tumors. Importantly, phosphoinositide 3-kinase
      inhibitor/protein kinase B (PI3K/AKT) pathway plays a key role in regulating Hh
      signaling by protecting key components of this pathway from proteasomal
      degradation. The levels of Hh-signaling molecules SMO and GLI1 and the targets
      were significantly elevated in tamoxifen-resistant MCF-7 cells and T47D cells.
      Serial passage of the resistant cells in mice resulted in aggressive tumors that
      metastasized to distant organs with concurrent increases in Hh marker expression
      and epithelial mesenchymal transition. RNAi-mediated depletion of SMO or GLI1 in
      the resistant cells resulted in reduced proliferation, clonogenic survival and
      delayed G(1)-S transition. Notably, treatment of resistant cells with PI3K
      inhibitors decreased SMO and GLI1 protein levels and activity that was rescued
      upon blocking GSK3beta and proteasomal degradation. Furthermore, treatment of
      tamoxifen-resistant xenografts with anti-Hh compound GDC-0449 blocked tumor
      growth in mice. Importantly, high GLI1 expression correlated inversely with
      disease-free and overall survival in a cohort of 315 patients with breast cancer.
      In summary, our results describe a signaling event linking PI3K/AKT pathway with
      Hh signaling that promotes tamoxifen resistance. Targeting Hh pathway alone or in
      combination with PI3K/AKT pathway could therefore be a novel therapeutic option
      in treating endocrine-resistant breast cancer.

PMID- 22875024
TI  - Functional genomics identifies drivers of medulloblastoma dissemination.
AB  - Medulloblastomas are malignant brain tumors that arise in the cerebellum in
      children and disseminate via the cerebrospinal fluid to the leptomeningeal spaces
      of the brain and spinal cord. Challenged by the poor prognosis for patients with
      metastatic dissemination, pediatric oncologists have developed aggressive
      treatment protocols, combining surgery, craniospinal radiation, and high-dose
      chemotherapy, that often cause disabling neurotoxic effects in long-term
      survivors. Insights into the genetic control of medulloblastoma dissemination
      have come from transposon insertion mutagenesis studies. Mobilizing the Sleeping
      Beauty transposon in cerebellar neural progenitor cells caused widespread
      dissemination of typically nonmetastatic medulloblastomas in Patched(+/-) mice,
      in which Shh signaling is hyperactive. Candidate metastasis genes were identified
      by sequencing the insertion sites and then mapping these sequences back to the
      mouse genome. To determine whether genes located at transposon insertion sites
      directly caused medulloblastomas to disseminate, we overexpressed candidate genes
      in Nestin(+) neural progenitors in the cerebella of mice by retroviral transfer
      in combination with Shh. We show here that ectopic expression of Eras, Lhx1,
      Ccrk, and Akt shifted the in vivo growth characteristics of Shh-induced
      medulloblastomas from a localized pattern to a disseminated pattern in which
      tumor cells seeded the leptomeningeal spaces of the brain and spinal cord.

PMID- 22875025
TI  - Soluble CD200 is critical to engraft chronic lymphocytic leukemia cells in
      immunocompromised mice.
AB  - CD200 is a transmembrane molecule with an important immunoregulatory role that is
      overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we
      characterized a previously unknown soluble form of this molecule in human plasma
      termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL
      as compared with healthy controls, and there was a significant correlation with
      CLL disease stage. Infusion of sCD200(hi) CLL plasma into severely
      immunocompromised NOD.SCIDgamma(c)(null) (NSG) mice enhanced the engraftment of
      CLL splenocytes as compared with mice receiving sCD200(lo) normal plasma. CLL
      cells were detected in both the spleen and peritoneal cavity of animals for up to
      75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma
      depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3
      monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL
      engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating
      engrafted CLL cells when administered 21 days after engraftment. Taken together,
      our findings point to sCD200 as a novel prognostic marker and therapeutic target
      for CLL. Furthermore, the humanized mouse model described here may prove valuable
      to preclinically assess new treatment regimens for CLL.

PMID- 22875026
TI  - FLT-PET is superior to FDG-PET for very early response prediction in NPM-ALK
      positive lymphoma treated with targeted therapy.
AB  - The prognosis of relapsed or refractory aggressive lymphoma is poor. The huge
      variety of currently evolving targeted treatment approaches would benefit from
      tools for early prediction of response or resistance. We used various ALK
      positive anaplastic large cell lymphoma (ALCL) cell lines to evaluate two
      inhibitors, the HSP90 inhibitor NVP-AUY922, and the mTOR inhibitor everolimus,
      both of which have shown to interfere with ALK-dependent oncogenic signal
      transduction. Their therapeutic effect was determined in vitro by MTT assay,
      [(18)F]fluorodeoxyglucose (FDG)- and [(18)F]fluorothymidine (FLT)-uptake, and by
      biochemical analysis of ALK-induced signaling. Micro-FDG- and FLT-positron
      emission tomography (PET) imaging studies in immunodeficient mice bearing ALCL
      xenotransplants were carried out with the cell lines SUDHL-1 and Karpas299 to
      assess early treatment response to NVP-AUY922 or everolimus in vivo. SUDHL-1
      cells showed sensitivity to both inhibitors in vitro. Importantly, we detected a
      significant reduction of FLT-uptake in SUDHL-1 bearing animals using both
      inhibitors compared with baseline as early as 5 days after initiation of targeted
      therapy. Immunostaining showed a decrease in Ki-67 and an increase in cleaved
      caspase-3 staining. In contrast, FDG-uptake did not significantly decrease at
      early time points. Karpas299 xenotransplants, which are resistant to NVP-AUY922
      and sensitive to everolimus treatment, showed an increase of mean FLT-uptake on
      day 2 after administration of NVP-AUY299, but a significant reduction in FLT
      uptake upon everolimus treatment. In conclusion, we show that FLT-PET but not FDG
      PET is able to predict response to treatment with specific inhibitors very early
      in the course of treatment and thus enables early prediction of treatment
      efficacy.

PMID- 22875028
TI  - Preventing and managing heel pressure ulceration: an overview.
AB  - Heel pressure ulcers are the second most common site for pressure ulceration;
      although their assessment and treatment can be complex, and they often require
      additional consideration over and above core principles of pressure ulcer
      prevention and management. Recent international pressure ulcer prevention and
      treatment guidelines developed jointly in Europe and the USA have provided
      greater clarity by achieving international consensus on how to care for patients
      at risk of heel pressure ulceration, and also on the management of such patients
      if a pressure ulcer develops. Health professionals should embrace these
      guidelines and embed them in their everyday clinical practice and within local
      guidance and protocols to ensure that patients are provided with evidence-based
      care supported by international collaboration and agreement.

PMID- 22875027
TI  - Individuals with non-specific low back pain in an active episode demonstrate
      temporally altered torque responses and direction-specific enhanced muscle
      activity following unexpected balance perturbations.
AB  - Individuals with a history of non-specific low back pain (LBP) while in a
      quiescent pain period demonstrate altered automatic postural responses (APRs)
      characterized by reduced trunk torque contributions and increased co-activation
      of trunk musculature. However, it is unknown whether these changes preceded or
      resulted from pain. To further delineate the relationship between cyclic pain
      recurrence and APRs, we quantified postural responses following multi-directional
      support surface translations, in individuals with non-specific LBP, following an
      active pain episode. Sixteen subjects with and 16 without LBP stood on two force
      plates that were translated unexpectedly in 12 directions. Net joint torques of
      the ankles, knees (sagittal only), hips, and trunk, in the frontal and sagittal
      planes, were quantified and the activation of 12 muscles of the lower limb
      unilaterally and the dorsal and ventral trunk, bilaterally, were recorded using
      surface electromyography (EMG). Peaks and latencies to peak joint torques, rates
      of torque development (slopes), and integrated EMGs characterizing baseline and
      active muscle contributions were analyzed for group by perturbation direction
      (torques) and group by perturbation by epoch interaction (EMG) effects. In
      general, the LBP cohort demonstrated APRs that were of similar torque magnitude
      and rate but peaked earlier compared to individuals without LBP. Individuals with
      LBP also demonstrated increased muscle activity following perturbation directions
      in which the muscle was acting as a prime mover and reduced muscle activity in
      opposing directions, proximally and distally, with some proximal asymmetries.
      These altered postural responses may reflect increased muscle spindle
      sensitivity. Given that these motor alterations are demonstrated proximally and
      distally, they likely reflect the influence of central nervous system processing
      in this cohort.

PMID- 22875029
TI  - Case study: treating an infected wound of unknown aetiology.
AB  - There are occasions when patients present with wounds where the aetiology is
      unknown. Planning care for these patients is dependent on the wound assessment
      and treating the clinical symptoms for example infection. Wound infection is
      often regarded as a challenging problem for clinicians and a considerable
      financial burden for the NHS (Patel, 2009). From a patient perspective, wound
      infection presents with unpleasant symptoms such as increased exudate, pain,
      swelling and malodour (Barrett et al, 2010). The introduction of antibiotics in
      the late 1940s and 1950s had a huge impact on the control of bacterial
      infections, however recently due to bacterial resistance, topical antimicrobials
      such as honey are starting to regain their appeal in the treatment of wound
      infection (Van der Weyden, 2003; Moffatt, 2006). The aim of this case study is to
      demonstrate how a honey dressing was used to treat an infected wound of unknown
      aetiology.

PMID- 22875030
TI  - Interview: Claire Stephens.

PMID- 22875032
TI  - Introducing Woundcare4Heroes.

PMID- 22875033
TI  - Managing exudate associated  with venous leg ulceration.
AB  - This review highlights the challenges associated with highly exuding venous leg
      ulcers for both the patient and the clinician. The main focus of the author's
      article is the management of heavy exudate levels, and key to this is the
      assessment process, which is discussed. The wide range of products and treatments
      available for managing high exudate levels are also explored. Despite these
      options, patients continue to suffer distress and the indignities of soiling of
      clothes, social embarrassment and reduced quality of life. The definition and
      composition of exudate is given, with particular emphasis on the damaging effects
      of chronic wound exudate. Reasons for high exudate and the priority of treating
      the underlying cause are discussed. Common themes examined are the assessment
      process, treating the underlying aetiology, the use of dressings and skin care.
      Complications of poor exudate management include a negative effect on the
      patient's quality of life, wound bed and periwound damage, increased risk of
      infection, increased costs to the health service and a delay in healing (Vowden
      and Vowden, 2003). Primary research and reviews are summarised, evaluating their
      significance to the various themes explored.

PMID- 22875034
TI  - Ionic-liquid-based MS probes for the chemo-enzymatic synthesis of
      oligosaccharides.
AB  - A new N-benzenesulfonyl-based ionic-liquid mass spectroscopy label (I-Tag2) for
      covalent attachment to substrates has been prepared. I-Tag2 was used to monitor
      oligosaccharide elongation and serve as a purification handle. Starting from
      chemically synthesized I-Tag2-labelled N-acetyl glucosamine (GlcNAc) 1, I-Tag2
      LacNAc (Galbeta(1-4)GlcNAc) 2 and I-Tag2-Lewis(X) (Galbeta(1-4)[Fucalpha(1
      3)]GlcNAc) 3, which are oligosaccharides of biological relevance, were
      enzymatically prepared. The apparent kinetic parameters for the enzyme catalysed
      transformations with beta-1,4-galactosyltransferase (beta-1,4-GalT) and
      fucosyltransferase VI (FucT VI) were measured by LC-MS demonstrating the
      applicability and versatility of the new I-Tags in enzymatic transformations with
      glycosyltransferases.

PMID- 22875035
TI  - Design and properties of functional nanotubes from the self-assembly of cyclic
      peptide templates.
AB  - beta-Sheet forming self assembling cyclic peptides offer a versatile scaffold for
      the construction and control of hydrogen-bonded nanotube assemblies. These
      structures have major advantages over other nanoscale tubular structures,
      including sub-nanometer control over the internal diameter, and the ability to
      control internal and external chemical functionality. This Tutorial Review
      presents an overview of nanotubes derived from this class of cyclic peptides. The
      design rationale for functional nanotubes based on cyclic peptide ring size and
      chemical functionality is discussed. Additionally, we highlight the recent
      expansion of the nanotube toolbox through conjugation of (macro)molecules to the
      cyclic peptides. These provide additional functionality and control nanotube
      dimensions that could potentially prove beneficial in future applications.

PMID- 22875038
TI  - Anatomical evaluation of the rectus femoris tendon and its related structures.
AB  - PURPOSE: The purpose of this study was to evaluate the anatomical structure of
      the quadriceps tendon in detail for use as an anterior cruciate ligament (ACL)
      graft tendon. MATERIALS AND METHODS: Sixteen cadaveric knees with an average age
      of 78.8 were used. After careful dissection of skin and fascia, the muscle
      structure of each quadriceps was evaluated. In particular, the rectus femoris
      (RF) tendon was measured at its widest and narrowest width, the distance between
      widest or narrowest point and the proximal end of the patella, and the length.
      RESULTS: The quadriceps tendon consisted of three layers. At the surface layer,
      the RF tendon existed mostly independently. The middle layer consisted of the
      vastus lateralis (VL) and medialis (VM) tendons. The deep layer consisted of the
      vastus intermedius (VI) tendon. The VL and VI tendons overlapped and were firmly
      connected, constituting the strength and size of the quadriceps. The narrowest
      width of the RF was 15.3 mm, and the narrowest point existed 4.8 mm proximal to
      the upper end of the patella. The average length of the RF was 27.3 cm.
      CONCLUSION: If the RF tendon only is used as an ACL graft, surgeons should be
      cautious of the fact that the narrowest point of the RF tendon is located close
      to the patella. The entire quadriceps tendon is big enough to be used as an ACL
      graft. However, since the direction of the VL and VI tendons is different, the
      suitability of the quadriceps tendon as an ACL graft is questionable.

PMID- 22875037
TI  - Outcome prediction using clinical scores and biomarkers in patients with presumed
      severe infection in the emergency department.
AB  - BACKGROUND: Severe infections play an important role in the emergency department
      (ED) and early risk stratification is essential. We compared the prognostic value
      of APACHE II, SOFA, and MEDS scores, and the biomarkers C-reactive protein (CRP),
      procalcitonin (PCT), and interleukin 6 (IL-6). METHODS: We performed a
      prospective observational study. Patients aged 18 years or older with a severe
      infection, from whom blood cultures were taken, were included. RESULTS: Two
      hundred and eleven patients were included. The 30-day mortality rate was 8.5%.
      All scores and biomarkers showed significant area under the curve (AUC) values of
      receiver operating characteristic curve analysis for death within 30 days: 0.801
      for APACHE II, 0.785 for MEDS, 0.708 for SOFA, 0.693 for CRP, 0.651 for PCT, and
      0.716 for IL-6. For treatment in an ICU and need for mechanical ventilation,
      these parameters had significant AUC values, too. For renal replacement therapy,
      only APACHE II, SOFA, and PCT showed significant AUC values. According to the
      trend observed, the AUC values were highest for the APACHE II score. CONCLUSIONS:
      All investigated parameters have a predictive value in patients with an infection
      in the ED. According to the trend observed, the APACHE II score seems to have the
      best discriminative power. Use of the APACHE II score already at the time of
      admission to the ED may be useful for stratifying patients at risk for ICU
      treatment, thereby using the same score in the ED and the ICU.

PMID- 22875039
TI  - Development of a novel class of B-Raf(V600E)-selective inhibitors through virtual
      screening and hierarchical hit optimization.
AB  - Oncogenic mutations in critical nodes of cellular signaling pathways have been
      associated with tumorigenesis and progression. The B-Raf protein kinase, a key
      hub in the canonical MAPK signaling cascade, is mutated in a broad range of human
      cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E)
      mutant exhibits elevated kinase activity and results in constitutive activation
      of the MAPK pathway, thus making it a promising drug target for cancer therapy.
      Herein, we describe the development of novel B-Raf(V600E) selective inhibitors
      via multi-step virtual screening and hierarchical hit optimization. Nine hit
      compounds with low micromolar IC(50) values were identified as B-Raf(V600E)
      inhibitors through virtual screening. Subsequent scaffold-based analogue
      searching and medicinal chemistry efforts significantly improved both the
      inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q
      possess nanomolar IC(50) values with selectivity for B-Raf(V600E)in vitro and
      exclusive cytotoxicity against B-Raf(V600E) harboring cancer cells.

PMID- 22875041
TI  - Oxacalix[3]arene-supported supertetrahedron.
AB  - The initial use of oxacalix[3]arene in manganese chemistry affords an unusual
      [Mn(10)] supertetrahedron with an even more unusual oxidation state distribution.

PMID- 22875040
TI  - Concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese
      medications: a population-based cohort study.
AB  - PURPOSE: We examined the extent of concurrent use of antiplatelets,
      anticoagulants, or digoxin with Chinese medications (CMs) and identified its
      associated factors. METHODS: A retrospective cohort study was conducted using one
      million random samples from the Longitudinal Health Insurance Database 2005 in
      Taiwan. High-risk Western medications (HRWMs) focused on in this study were
      antiplatelets (aspirin, clopidogrel, dipyridamole, ticlopidine), anticoagulants
      (heparin, warfarin), and digoxin. Concurrent use was described as having an
      overlapping use period of HRWM with CMs any time in 2005. Baseline demographics,
      comorbidities, and health service utilizations between patients with and without
      concurrent HRWM-CM use were compared. Logistic regression analyses were performed
      to identify factors associated with incident concurrent use. RESULTS: Of the
      70,698 eligible HRWM users, 13.2 % used CMs concurrently for an average duration
      of 26.7 +/- 43 days. The incidence of concurrent HRWM-CM use, which excluded
      prior CM use within 6 months preceding the first CM use, was 6.3 %. Warfarin or
      ticlopidine users were more likely to be prescribed with CMs than were the other
      HRWM users. Factors associated with an increasing incidence of concurrent HRWM-CM
      use included female sex, age 45-54 years, middle monthly income, higher number of
      outpatient visits or distinct prescribed medications, and a previous diagnosis of
      heart diseases, stroke, or hypertension. In contrast, age >= 65 years and higher
      medical expenditure were associated with a lower incidence of concurrent use.
      CONCLUSIONS: In the Taiwanese population, approximately one in eight HRWM users
      were concomitantly prescribed CMs. Whether such concurrent use is associated with
      adverse clinical outcomes warrants further investigations.

PMID- 22875042
TI  - Statistical modeling of crystalline silica exposure by trade in the construction
      industry using a database compiled from the literature.
AB  - A quantitative determinants-of-exposure analysis of respirable crystalline silica
      (RCS) levels in the construction industry was performed using a database compiled
      from an extensive literature review. Statistical models were developed to predict
      work-shift exposure levels by trade. Monte Carlo simulation was used to recreate
      exposures derived from summarized measurements which were combined with single
      measurements for analysis. Modeling was performed using Tobit models within a
      multimodel inference framework, with year, sampling duration, type of
      environment, project purpose, project type, sampling strategy and use of exposure
      controls as potential predictors. 1346 RCS measurements were included in the
      analysis, of which 318 were non-detects and 228 were simulated from summary
      statistics. The model containing all the variables explained 22% of total
      variability. Apart from trade, sampling duration, year and strategy were the most
      influential predictors of RCS levels. The use of exposure controls was associated
      with an average decrease of 19% in exposure levels compared to none, and
      increased concentrations were found for industrial, demolition and renovation
      projects. Predicted geometric means for year 1999 were the highest for drilling
      rig operators (0.238 mg m(-3)) and tunnel construction workers (0.224 mg m(-3)),
      while the estimated exceedance fraction of the ACGIH TLV by trade ranged from 47%
      to 91%. The predicted geometric means in this study indicated important
      overexposure compared to the TLV. However, the low proportion of variability
      explained by the models suggests that the construction trade is only a moderate
      predictor of work-shift exposure levels. The impact of the different tasks
      performed during a work shift should also be assessed to provide better
      management and control of RCS exposure levels on construction sites.

PMID- 22875043
TI  - TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source
      for dendritic cell-like antigen-presenting cells.
AB  - We previously reported a method to generate dendritic cell (DC)-like antigen
      presenting cells (APC) from human induced pluripotent stem (iPS) cells. However,
      the method is relatively complicated and laborious. In the current study, we
      attempted to establish a method through which we could obtain a large number of
      functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+)
      myeloid cells with genes associated with proliferative or anti-senescence
      effects, enabling the cells to propagate for more than 4 months in a macrophage
      colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity
      to differentiate into functional APC. We named these iPS cell-derived
      proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In
      addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease
      aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided
      recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC
      expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART
      1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors,
      resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines.
      TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an
      unlimited source of APC for vaccination therapy. If administered into allogeneic
      patients, ML-DC with appropriate genetic modifications may survive long enough to
      stimulate antigen-specific CTL and, after that, be completely eliminated. Based
      on the present study, we propose an APC-producing system that is simple, safe and
      applicable to all patients irrespective of their HLA types.

PMID- 22875044
TI  - Nanocomposites and macroscopic materials: assembly of chemically modified
      graphene sheets.
AB  - Self-assembly of chemically modified graphenes (CMGs), including graphene oxide
      (GO), reduced graphene oxide (RGO) and their derivatives, has emerged as one of
      the most appealing strategies to develop unprecedented graphene-based functional
      materials. With the assistance of various non-covalent forces such as hydrogen
      bonding, ionic, amphiphilic and pi-pi interactions, CMGs decorated with multiple
      functional groups are favorable for assembly with different organic and inorganic
      components which can result in hierarchical composites possessing unique
      structures and functions. In this review, we will summarize the state-of-the-art
      self-assembly strategies that have been established to construct CMG based
      nanomaterials, including nanoparticles, nanospheres, nanofibers, nanorods,
      nanosheets, and macroscopic thin films, fibers and porous networks. The driving
      forces involved in the self-assembly process will be elucidated in the context.
      Further, we will also highlight several representative examples of applications
      regarding the self-assembled CMG based materials.

PMID- 22875046
TI  - A ratiometric fluorescence sensor for caffeine.
AB  - The dye disodium 3,4:3',4'-bibenzo[b]thiophene-2,2'-disulfonate can be used as a
      molecular probe for the fluorimetric detection of caffeine in aqueous solution.
      The fluorescence response is attributed to non-covalent interactions of caffeine
      with the dye in the ground state and in the excited state. The bimodal
      interaction allows performing ratiometric measurements with very good selectivity
      over structurally related analytes. The dye was also used to develop a simple
      test strip for the visual differentiation of normal and decaffeinated coffee with
      a standard UV lamp.

PMID- 22875047
TI  - Usefulness of additional fetal magnetic resonance imaging in the prenatal
      diagnosis of congenital abnormalities.
AB  - OBJECTIVE: Our aim was to compare the value of fetal magnetic resonance imaging
      (MRI) with detailed ultrasound in the prenatal diagnosis of congenital
      abnormalities. MATERIALS AND METHODS: This retrospective study reviewed the
      medical records of pregnant women and their neonates who, after ultrasound, were
      suspected to have congenital abnormalities. They then underwent a detailed
      ultrasound examination and a fetal MRI in our institutions. Fetal MRI was
      performed in 81 cases. Each prenatal presumptive diagnosis, based on detailed
      ultrasound examination and fetal MRI, was compared with the postnatal confirmed
      diagnosis. In 58 cases, the data collected were confirmed by the postnatal
      diagnosis. RESULTS: Supplemental information from fetal MRI was useful in 17 of
      the 22 cases involving the central nervous system (CNS), two of two cases
      involving the thorax, nine of nine cases involving the genitourinary system, two
      of eight cases involving the gastrointestinal system, and ten of ten cases
      involving complex malformations. Fetal MRI did not provide significantly useful
      information or facilitate a more accurate diagnosis except for CNS abnormalities.
      CONCLUSION: Fetal MRI was not superior to an ultrasound examination in the
      prenatal detection of congenital abnormalities. A detailed ultrasound examination
      performed by experienced obstetricians had satisfactory accuracy in the diagnosis
      of fetal abnormalities compared with fetal MRI. Fetal MRI might be useful in
      appropriate cases in Korea. Greater effort is required to increase the ultrasound
      knowledge and skill of competent obstetricians.

PMID- 22875048
TI  - Early embryonic morphology sonographically assessed and its correlation with yolk
      sac in missed abortion.
AB  - PURPOSE: To provide additional information about embryo morphology sonographic
      assessment and its correlation with yolk sac. METHODS: A systematic study in 200
      consecutive cases of missed abortion <10 weeks diagnosed by transvaginal
      ultrasound. RESULTS: In 104 gestations of embryos with morphological
      abnormalities, 88 (84.6 %) were at least 1 week smaller than expected for
      gestational age and 16 (15.4 %) were the expected size. From 32 normal
      morphologic embryos, 7 (21.9 %) were at least 1 week smaller than expected for
      gestational age, and 25 (78.1 %) were the expected size (p < 0.005). Normal
      morphologic embryos are linked more frequently with normal yolk sac (62.5 %).
      Findings in anembryonic gestations (GD1) included an absent yolk sac (46.9 %) and
      a cystic yolk sac (25 %). Likewise, findings in GD2-3 embryos included more
      frequently a cystic yolk sac (42.9 %) and an absent yolk sac (32.5 %). GD4
      embryos are associated with an echogenic yolk sac (40 %), a relatively small
      hypoplastic- (40 %) and a relatively large-cystic- (20 %). In DI embryos, yolk
      sac appears cystic (62.5 %) or echogenic (37.5 %). CONCLUSIONS: Our study proves
      the correlation between morphology of conceptuses and yolk sac appearance in
      cases of missed abortion.

PMID- 22875049
TI  - First-trimester serum folate levels and subsequent risk of abortion and preterm
      birth among Japanese women with singleton pregnancies.
AB  - OBJECTIVES: To determine whether a low serum folate level during the first
      trimester predicts subsequent late abortion, preterm birth, or fetal growth
      restriction (FGR). STUDY DESIGN: A prospective cohort study involving 5,075 women
      whose serum folate levels were measured during the first trimester. The
      participants were informed of their serum folate levels. RESULTS: The pregnancy
      duration, birthweight, rate of late abortion/preterm birth, and the rate of FGR
      did not differ significantly among the four groups classified according to folate
      status. The mean serum folate levels did not differ among quartiles classified
      according to the gestational week at the time of delivery. Nineteen of the 20
      women with folate deficiency gave birth at term to infants with a birthweight of
      3.132 +/- 321 g; only one infant had FGR. CONCLUSION: Low serum folate levels
      during the first trimester were not associated with the risk of late abortion,
      preterm birth, or FGR.

PMID- 22875050
TI  - Usefulness of Finasteride to induce ovulation in a non responder hyperandrogenic
      woman: birth of a healthy male infant.

PMID- 22875051
TI  - The superomedial bare area of the costal scapula surface: a possible cause of
      snapping scapula syndrome.
AB  - PURPOSE: Scapulothoracic bursitis is a painful condition of the scapulothoracic
      articulation, which may be caused by various pathological anatomical
      associations. We have arthroscopically observed a constant bare area of bone on
      the costal scapula surface in patients with scapulothoracic bursitis,
      contradictory to traditional anatomical reports of scapular muscle relations. We
      undertook a cadaveric study to further define this anatomical feature. METHODS:
      Twelve cadaveric shoulders were dissected. The costal surface of the scapula was
      systematically examined for the presence of a superomedial bare area in each
      shoulder by three independent clinicians, with dimensions measured using digital
      calipers. RESULTS: In all shoulders, there was a clearly defined bare area of
      bone on the superomedial aspect of the costal surface of the scapula between the
      serratus anterior insertion and subscapularis origin. The bare area was typically
      crescenteric in shape, with variable length (mean 22.3 +/- 6.0 mm) and width
      (10.8 +/- 2.8 mm). The bare area length (p = 0.043) and width (p = 0.033) were
      significantly greater in female shoulders compared to male shoulders.
      CONCLUSIONS: We have established the presence of the superomedial bare area of
      the costal scapula surface. With an absence of overlying subscapularis muscle,
      this bare area carries the potential for scapulothoracic impingement, and should
      be considered as a possible aetiological factor in all patients presenting with
      scapulothoracic bursitis.

PMID- 22875053
TI  - [Importance of Strahlentherapie und Onkologie for Swiss radiation oncology].

PMID- 22875052
TI  - Cellular and molecular properties of (90)Y-labeled cetuximab in combination with
      radiotherapy on human tumor cells in vitro.
AB  - PURPOSE: Anti-EGFR antibody cetuximab (C225) is used in combination with
      radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We
      investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene
      triamine-pentaacetic acid (CHX-A"-DTPA) and radiolabeling with (90)Yttrium affect
      the molecular and cellular function of cetuximab and improve its combined effect
      with external-beam irradiation (EBI). METHODS: The following cell lines were
      used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO),
      and human skin fibroblast HSF7. Binding affinity and kinetics, specificity,
      retention, and the combination of (90)Y-cetuximab with EBI were evaluated.
      RESULTS: Control cetuximab and CHX-A"-DTPA-cetuximab blocked the proliferation
      activity of UT5 cells. In combination with EBI, CHX-A"-DTPA-cetuximab increased
      the radiosensitivity of UT5 to a similar degree as control cetuximab did. In
      contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was
      affected by either of the antibodies. Binding [(90)Y]Y-CHX-A"-DTPA-cetuximab
      ((90)Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum
      binding at 24 h. Retention of (90)Y-cetuximab was similar in both HNSCC cell
      lines; 24 h after treatment, approximately 90% of bound activity remained in the
      cell layer. Competition assays, using cell membranes in the absence of an
      internalized fraction of cetuximab, showed that the cetuximab affinity is not
      lost as a result of conjugation with CHX-A"-DTPA. Cetuximab and CHX-A"-DTPA
      cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an
      effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the
      inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by
      cetuximab were not affected by DTPA conjugation. (90)Y-cetuximab in combination
      with EBI resulted in a pronounced inhibition of colony formation of HNSCC cells.
      CONCLUSIONS: Conjugation of CHX-A"-DTPA to cetuximab does not alter the cellular
      and biological function of cetuximab. (90)Y-labeling of cetuximab in combination
      with EBI may improve radiotherapy outcome.

PMID- 22875054
TI  - Rhodium acetate/base-catalyzed N-silylation of indole derivatives with
      hydrosilanes.
AB  - In the presence of Rh(2)(OAc)(4) (OAc = acetate) and TBA(2)WO(4) (TBA = tetra-n
      butylammonium), the N-silylation of indole derivatives with hydrosilanes
      efficiently proceeded to give the corresponding N-silylated indoles in high
      yields. Pyrrole and carbazole were also N-silylated with the combined catalysts.

PMID- 22875055
TI  - Two new palladium(II) complexes: synthesis, characterization and their
      interaction with HeLa cells.
AB  - Two complexes [Pd(L(1))(en)](2).4H(2)O (1), [Pd(L(2))(en)].2H(2)O (2), (L(1) =
      pyridine-2,3-dicarboxylic acid, L(2) = pyrazine-2,3-dicarboxylic acid, and en =
      ethylenediamine) have been synthesized and characterized using IR, (1)H NMR and
      element analysis. X-ray analyses of complexes 1 and 2 revealed that 1 belongs to
      the triclinic system with space group P1(2), and 2 belongs to the monoclinic
      system with space group P2(1)/n. The binding of the complexes with HC-DNA (HeLa
      cells DNA, which was extracted by ourselves) were measured by fluorescence
      spectrum and viscometry. Gel electrophoresis assay demonstrates the ability of
      the complexes to cleave the extracted HC-DNA. The complexes exhibit a higher
      cytotoxicity against tumor cells as against normal cells in vitro. Further more,
      apoptotic tests indicate that the complexes have an apoptotic effect on HeLa
      cells.

PMID- 22875056
TI  - The feasibility and efficacy of endovascular treatment for very small or tiny
      ruptured paraclinoid aneurysms.
AB  - INTRODUCTION: The aim of this study was to evaluate the feasibility of
      endovascular treatment (EVT) for ruptured very small (<=5 mm) or tiny (<=3 mm)
      paraclinoid aneurysms of the internal carotid artery (ICA). METHODS: From
      November 2009 to April 2012, 32 ruptured paraclinoid aneurysms (very small, 23;
      tiny, 9) in 31 patients received EVT. Angiographic follow-up determined occlusion
      rates which were classified as total/near-total (95-100 %), subtotal (80-95 %),
      and partial (<80 %) occlusions. Follow-up data were retrospectively analyzed and
      categorized using the Modified Rankin Scale (mRS). RESULTS: Based on our
      paraclinoid aneurysm classification, 25 % (8) were classified as type I, 46.9 %
      (15) as type II, and 28.1 % (9) as type III. EVT was technically successful in
      96.8 % (31), with coiling only in 12.5 % (4), balloon remolding coiling in 6.3 %
      (2), and stent-assisted coiling in 78.1 % (25). Total/near-total occlusion was
      immediately achieved in 34.4 % (11), subtotal occlusion in 37.5 % (12), and
      partial occlusion in 28.1 % (9). Follow-up angiography (mean, 9.9 +/- 6.4 months)
      revealed total/near-total occlusion in 50 % (16) aneurysms, subtotal in 31.3 %
      (10), and partial occlusion in 18.8 % (6). At the end of clinical follow-up
      (mean, 14.8 +/- 9.5 months), it revealed an mRS grade 0 in 38.7 % (12) of
      patients, grade 1 in 25.8 % (8), grade 2 in 22.6 % (7), grade 3 in 6.5 % (2),
      grade 4 in 3.2 % (1), and grade 5 in 3.2 % (1). CONCLUSION: EVT is feasible and
      effective for ruptured very small or tiny paraclinoid aneurysms of the ICA.

PMID- 22875057
TI  - Novel approach to biscarbazole alkaloids via Ullmann coupling--synthesis of
      murrastifoline-A and bismurrayafoline-A.
AB  - Unprecedented Ullmann couplings of murrayafoline-A with either 6-bromo- or 4
      bromocarbazole derivatives provide highly efficient synthetic routes to the
      biscarbazole alkaloids murrastifoline-A (6 steps, 66% overall yield) and
      bismurrayafoline-A (6 steps, 28% overall yield).

PMID- 22875059
TI  - [Primum non nocere : how deep can we allow general anaesthesia to be?].

PMID- 22875058
TI  - [Anesthesia in endourological and robot-assisted interventions].
AB  - The improved drug therapy leads to increasingly older patients with complex
      comorbidities in the discipline of operative urology. Today, improved technical
      equipment provides new operational capabilities in the field of urology. The
      prone and lithotomy position during surgery leads to physiological changes that
      affect anesthesia management. The surgical risk of procedures such as
      transurethral surgery of the prostate or bladder is being altered by laser
      surgery and other new technologies. Although the incidence of transurethral
      resection (TUR) syndrome has been reduced in recent years, the intrusion of
      irrigation fluid still has to be considered during anesthesia. Robot-assisted
      surgery has successfully completed the experimental stage and is widely used so
      that new targets have to be challenged. Ureterorenoscopy is performed with
      flexible, small caliber ureteroscopes which even allow treatment of renal calculi
      under analgosedation within short time periods. Percutaneous nephrostomy and
      litholapaxy are still frequently performed in the prone position. With respect to
      the risks arising from patient positioning, supine or lateral positioning should
      be considered in individual cases. A good communication between the surgeon and
      anesthetist allows deviation from daily routine procedures if special indications
      require a modified approach. In conclusion, a profound knowledge of the (patho
      )physiology of general anesthesia and endourological diseases enables
      anesthetists to provide a prospective type anesthesia, which should prevent the
      occurrence of life-threatening incidents.

PMID- 22875060
TI  - [Modified rapid sequence induction for Caesarian sections : case series on the
      use of rocuronium and sugammadex].
AB  - BACKGROUND: Aspiration is a feared complication of anesthesia and is accompanied
      by increased morbidity and mortality. Rapid sequence induction (RSI) describes
      the preferred procedure to perform endotracheal placement of the tubus in
      emergency cases of patients with an increased risk of aspiration of gastric
      contents. For more than 50 years RSI has consisted of the application of
      suxamethonium for neuromuscular blockade because of its fast onset and ultra
      short duration. Due to the serious side effects of suxamethonium attempts were
      made to find better alternative neuromuscular blocking drugs, e.g. rocuronium, to
      perform RSI. MATERIALS AND METHODS: In this small clinical series RSI was
      performed for general anesthesia of ten pregnant women for Caesarean sections
      using 1.0 mg/kgBW rocuronium for induction and maintaining deep relaxation until
      the end of surgery. For rapid reversal of the neuromuscular blockade to a train
      of-four (TOF) ratio of 0.9, the u-cyclodextrin sugammadex was administered at the
      end of surgery. Major and minor side effects, such as cardiac dysrhythmia,
      anaphylactic reactions, hoarseness and postoperative nausea and vomiting were
      documented. CONCLUSIONS: The combination of rocuronium and sugammadex for RSI
      combines rapid onset and rapid reversal of neuromuscular blockades with avoidance
      of serious side effects and very comfortable conditions for intubation in all
      cases. Minor side effects such as hoarseness, throat discomfort (in up to 30%)
      and myalgia (10%) for up to 48 h were documented.

PMID- 22875061
TI  - [Dual antiplatelet therapy and operative medicine : open questions despite
      guidelines?].

PMID- 22875062
TI  - Simultaneous analysis of the expression of 14 genes with individual prognostic
      value in myelodysplastic syndrome patients at diagnosis: WT1 detection in
      peripheral blood adversely affects survival.
AB  - Several studies have evaluated the prognostic value of the individual expression
      of certain genes in patients with myelodysplastic syndromes (MDS). However, none
      of them includes their simultaneous analysis by quantitative polymerase chain
      reaction (PCR). We evaluated relative expression levels of 14 molecular markers
      in 193 peripheral blood samples from untreated MDS patients using real-time PCR.
      Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the
      only markers showing in univariate analysis a poor prognostic value for all
      treatment-free (TFS), progression-free (PFS), and overall survival (OS). In
      multivariate analysis, molecular parameters associated with a shorter TFS were:
      WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p =
      0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were
      associated with a shorter PFS when multivariate analysis was carried out by
      including only molecular markers. Molecular values with an independent value in
      OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and
      undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with
      adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable
      molecular expression profile. In summary, detectable WT1 expression levels, and
      low TET2 and low IER3 expression in peripheral blood showed a strong association
      with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only
      molecular marker displaying an independent prognostic value in both OS and TFS.

PMID- 22875063
TI  - Renal failure secondary to leukemic infiltration of kidneys in CLL--a case report
      and review of literature.

PMID- 22875065
TI  - Role of steroids in reducing postoperative edema in rhinoplasty: a meta-analytic
      study.
AB  - The study aimed at verifying the use of steroids to decrease postoperative edema
      after rhinoplasty. The study included published articles yielded by the Medline
      database search concerning role of steroids in rhinoplasty. The search was
      limited to articles published in English in the last three decades. The search
      was done on 1/2/2012. For the 15 relevant articles, we applied our inclusion and
      exclusion criteria and only four articles were included. The data collected from
      each article were statistically analyzed utilizing meta-analytic Review manager
      (RevMan 5.1) software (Version: 5.1.0.0). Perioperative steroid use significantly
      reduces postoperative edema of the upper and lower eyelids on the first and third
      days postoperative, with no significant effect after third day. The results
      indicated that steroids should be given for patients undergoing rhinoplasty for
      decreasing periorbital edema postoperatively especially in the first 3 days,
      however, it has little effect after the third day.

PMID- 22875064
TI  - Laryngeal pacing in minipigs: in vivo test of a new minimal invasive
      transcricoidal electrode insertion method for functional electrical stimulation
      of the PCA.
AB  - Functional electrical stimulation (FES) of the posterior cricoarytenoid muscle
      (PCA) to restore respiratory function of the larynx may become an option for the
      treatment of bilateral recurrent laryngeal nerve paralysis (RLNP) in the near
      future. The feasibility of this has been shown in several animal trials and in a
      human pilot study. The common open surgical inferolateral approach for electrode
      insertion into the PCA for FES has a risk of damaging the recurrent laryngeal
      nerve (RLN) and may result in postoperative swelling and scaring of the larynx.
      Therefore, a minimal invasive electrode insertion technique is needed. A new
      miniaturized bipolar spiral tip electrode and a new electrical stimulatable
      insertion needle were tested in a short-term trial for an endoscopically guided
      and functionally controlled transcricoidal electrode insertion in eight Gottingen
      minipigs with bilateral normal RLN function. The feasibility of this technique
      was evaluated and the achieved positions of the electrodes in the PCA were
      analyzed using intraoperative stimulation threshold data and 3D-CT
      reconstructions. In seven cases it was possible to place two well-performing
      electrodes into the PCA. They were positioned one on either side. In one animal
      no functioning electrode position could be achieved because the PCA was missed.
      Thresholds of the electrode tips varied between 0.2 and 2.5 mA (mean 0.71 mA). In
      any case maximal glottal opening could be reached before adductors were co
      activated. The majority of electrodes were placed into the central lower part of
      the PCA with no apparent correlation between threshold and electrode position.
      Surgical trauma might be further reduced by using endoscopy via a laryngeal mask
      avoiding the temporary tracheostomy used in this trial. If the implanted
      electrodes remain stable in long-term tests, we suggest that this method could
      soon be transferred into human application.

PMID- 22875066
TI  - Sialoendoscopy and combined approach for the management of salivary gland stones.
AB  - The introduction of minimally invasive surgical procedures has significantly
      reduced the rate of major salivary gland removal due to sialolithiasis. The aim
      of this study is to assess the effectiveness of sialoendoscopy, rate of salivary
      fistula or natural ostium stenosis in parotid sialolithiasis treatment. The
      endpoint was to analyse the efficiency of a combined transcutaneous and
      endoscopic approach in the removal of refractory and impacted stones in most
      difficult cases. STUDY DESIGN: prospective study, tertiary university centre,
      between XII 2008 and XI 2011, 185 sialendoscopies (SE) were performed in 162
      patients. Within the group of 29 patients with parotid sialolithiasis endoscopy
      was the definite treatment in 15 cases (53 %), in 9 cases lithotripsy (ESWL) was
      necessary and in 5 patients who failed SE and lithotripsy, a combined approach
      was performed. This approach comprised both SE and open surgery. We observed no
      salivary fistula formation after the incision of the duct. Stenosis of the
      natural ostium thanks to the insertion of stent was observed only in one case.
      Sialoendoscopy is the method of choice with a high rate of success and gland
      preservation in small and medium stones. The combined transcutaneous and
      endoscopic approach is indicated for large stones, for complications after and
      contraindications in using minimally invasive procedures. Short and medium term
      follow up shows that surgery can be performed with a high rate of success.

PMID- 22875067
TI  - Central blood pressure: a powerful predictor of the development of hypertension.
AB  - We examined whether the central aortic systolic blood pressure, a marker of the
      function of the systemic arterial tree, might be a more powerful predictor of the
      development of hypertension than the brachial-ankle pulse wave velocity, a marker
      of the stiffness of the large- to middle-sized arteries, independent of the
      conventional risk factors for the development of hypertension. In 1268 Japanese
      men without hypertension (43+/-8 years old), the relationships between three
      variables (the second peak of the radial pressure waveform (SP2), brachial-ankle
      pulse wave velocity and conventional risk factors measured at the first
      examination) with the presence of hypertension at the second examination (after 3
      years' follow-up) were examined. Hypertension was detected at the second
      examination in 154 men. The best cutoff points of the brachial-ankle pulse wave
      velocity and SP2, for predicting the development of hypertension, were 12.7 m/s
      and 109 mm Hg, respectively. The results of a logistic regression analysis
      confirmed that an SP2 of >=109 mm Hg (odds ratio=8.493, P<0.001) was a more
      powerful predictor of the development of hypertension than a brachial-ankle pulse
      wave velocity of >=12.7 m/s, independent of the conventional risk factors. The
      net reclassification index of SP2 (at the best cutoff point) to brachial-ankle
      pulse wave velocity was 0.211 (P<0.001), indicating that SP2 is a better
      predictor of the development of hypertension than brachial-ankle pulse wave
      velocity. In middle-aged Japanese men without hypertension, SP2 may be a more
      powerful predictor of the development of hypertension than the assessment of
      stiffness in large to middle-sized arteries independent of the conventional risk
      factors.

PMID- 22875068
TI  - Cardiopulmonary exercise testing and its relation to oxidative stress in patients
      with hypertension.
AB  - An increase in reactive oxygen species has been implicated in the pathologies of
      hypertension. This study was designed to evaluate antioxidant activity in
      hypertensive patients and to assess the relationship between oxidative stress and
      exercise tolerance in hypertensive patients with mild left ventricular diastolic
      dysfunction (LVDD). A total of 42 patients, aged 51+/-9 years, with a long
      history of hypertension and mild LVDD (mitral flow velocities-E/A <1,
      deceleration time of E >220 ms, and preserved ejection fraction-EF >50%), and 30
      controls without cardiovascular disease, aged 50+/-7 years, underwent
      cardiopulmonary exercise testing (CPET). Peak oxygen uptake (peak VO(2)), oxygen
      pulse (VO(2)/heart rate (HR)) and ventilatory anaerobic threshold (VAT) were
      obtained during CPET. Antioxidant activity of superoxide dismutase (SOD) and
      glutathione peroxidase in the blood was measured before and after exercise.
      Reduced peak VO(2) (1715+/-426 vs. 2083+/-465 ml min(-1), P<0.001), VO(2)/HR
      (12.0+/-2.8 vs. 14.6+/-3.3 ml per beat, P<0.001) and percentage of peak VO(2) at
      VAT (55.5+/-15.8% vs. 64.5+/-14.7%, P=0.007) were observed in hypertensive
      patients, compared with controls. Antioxidant protection was significantly
      attenuated in hypertensive patients, compared with controls, before (945 vs.
      1006, P=0.012) and after exercise (954 vs. 1051, P<0.001). The level of SOD
      before and after exercise was significantly associated with LVDD in hypertensive
      patients (P=0.012 and 0.02, respectively). In addition, the degree of LVDD before
      exercise (E/A) influenced the degree of exercise capability (peak VO(2))
      (P=0.016). Asymptomatic hypertensive patients with mild LVDD had reduced
      cardiopulmonary capacity, accurately identified by CPET. The redox state in
      hypertensive patients was significantly related to LVDD and exercise tolerance.
      Attenuated antioxidant protection was associated with long-term hypertension.

PMID- 22875069
TI  - Hypertension and C-reactive protein.

PMID- 22875070
TI  - Comparison of 12-lipoxygenase expression in vascular smooth muscle cells from old
      normotensive Wistar-Kyoto rats with spontaneously hypertensive rats.
AB  - Vascular aging and essential hypertension cause similar structural and molecular
      modifications in the vasculature. The 12-lipoxygenase (LO) pathway of arachidonic
      acid metabolism is linked to cell growth and the pathology of hypertension. Thus,
      elevated expression of 12-LO has been observed in vascular smooth muscle cells
      (VSMCs) from spontaneously hypertensive rats (SHR). In the present study, we
      investigated the differences in 12-LO expression and activity between VSMCs from
      old normotensive Wistar-Kyoto rats (old WKY, 90-week old) and SHR (13-week old).
      The protein and mRNA expression of basal or angiotensin II (Ang II)-induced 12-LO
      in old WKY VSMCs were higher than those in SHR VSMCs. The degradation rate of 12
      LO mRNA in old WKY VSMCs was slower than that in SHR VSMCs. However, basal or Ang
      II-induced 12-LO mRNAs in both old WKY and SHR VSMCs decayed more rapidly than
      that in young WKY (13-week old) VSMCs. Higher expression of 12-LO in old WKY
      VSMCs than in SHR VSMCs was correlated with the expression level of Ang II
      subtype 1 receptor (AT(1)R). The reduced levels of nitric oxide (NO) in old WKY
      and SHR VSMCs compared with young WKY VSMCs were similar, and there was no
      significant difference in NO production between old WKY and SHR VSMCs transfected
      with 12-LO siRNA. In addition, in contrast to the proliferation of SHR VSMCs, the
      proliferation of old WKY VSMCs was not dependent on 12-LO activation. These
      results suggest that the potential role of 12-LO in normotensive aging
      vasculature may be different from that in SHR vasculature.

PMID- 22875071
TI  - Automated oscillometric measurement of the ankle-brachial index in patients with
      coronary artery disease.
AB  - Automated oscillometric ankle-brachial index (ABI) devices were designed to
      measure ABI in a primary-care setting to increase the peripheral artery disease
      (PAD) detection rate. However, ABI measurements obtained with an automated
      oscillometric device may differ from those obtained using a standard ultrasound
      Doppler method in the general population. The purpose of this study was to
      compare PAD detection by the Doppler method and the automated WatchBP Office ABI
      system in a high-risk population with coronary artery disease (CAD). Eighty
      consecutive patients with confirmed CAD were included. ABI was measured by
      automated oscillometry followed by conventional Doppler evaluation. PAD was
      defined as an ABI<=0.9. Each lower extremity was analyzed separately. The Doppler
      method detected an ABI<=0.9 in 56 lower extremities, whereas the automated method
      detected an ABI<=0.9 in 28 lower extremities (P<0.0001). A Bland-Altman plot
      showed poor agreement between the two methods. The mean ABI values obtained by
      the automated and Doppler methods were significantly different (1.11+/-0.20 vs.
      0.95+/-0.24; P<0.00001). The sensitivity of the automated ABI device in detecting
      an ABI<=0.9 was 46.3% and the specificity was 98.0%. The positive and negative
      predictive values for diagnosing an ABI<=0.9 using the automated oscillometric
      method were 92.8% and 76.9%, respectively. In conclusion, the automated WatchBP
      Office ABI system should be used with caution for PAD detection and screening in
      patients with CAD, and this system should not replace the Doppler method in
      populations at high risk of cardiovascular disease.

PMID- 22875072
TI  - Heteroaromatic donors in donor-acceptor-donor based fluorophores facilitate zinc
      ion sensing and cell imaging.
AB  - The excited state intra molecular charge transfer (ICT) property of fluorophores
      has been extensively used for the design of fluorescent chemosensors. Herein, we
      report the synthesis and properties of three donor-pi-acceptor-pi-donor (D-pi-A
      pi-D) based molecular probes BP, BT and BA. Two heteroaromatic rings, pyrrole
      (BP), and thiophene (BT) and a non-heteroaromatic ring N-alkoxy aniline (BA) were
      selected as donor moieties which were linked to a bipyridine binding site through
      a vinylic linkage. The heteroaromatic systems BP and BT perform selective and
      ratiometric emission signalling for zinc ions whereas the non-heteroaromatic
      probe BA does not. The advantages of the D-pi-A-pi-D design strategy in the
      design of ICT based probes for the selective fluorescent ratiometric signalling
      of zinc ions in biological media is discussed. Further, the use of BP, BT and BA
      for imaging Zn(2+) ions from MCF-7 cell lines is demonstrated.

PMID- 22875076
TI  - Estimation of age from human sternum: an autopsy study on a sample from South
      India.
AB  - Age estimation is one of the main parameters in the evaluation of skeletal
      remains in forensic anthropology casework. The present investigation is an
      attempt to study the fusion of manubrium and xiphoid process with mesosternum in
      118 sterna (67 males and 51 females) of known age obtained during autopsy in
      South Indian population. The male samples were aged between 25 and 74 years and
      the females between 20 and 80 years. The fusion is studied to derive standards
      for the estimation of age from sternum. The results indicate that, with advancing
      age, the proportion of sternum with fusion of manubrio-mesosternal and mesosterno
      xiphisternal junctions increases in males and females. A larger proportion of
      sterna showed fusion of mesosterno-xiphisternal junction than manubrio
      mesosternal junction in different age groups. Fusion of manubrio-mesosternal and
      mesosterno-xiphisternal junctions was proportionately commoner in males than
      females. None of the sterna aged below 30 years showed fusion of mesosterno
      xiphisternal junction. Nonfusion of mesosterno-xiphisternal junction was reported
      till the age of 48 years in males and 46 years in females. Manubrio-mesosternal
      junction was observed to be very variable with regard to fusion status as the
      joint remained unfused even in the elderly ages. Based on the variability of the
      fusion of manubrio-mesosternal and mesosterno-xiphisternal junctions observed in
      the study, it can be concluded that the sternum alone is not reliable for
      estimation of age in South Indian population.

PMID- 22875077
TI  - Is informal caregiving independently associated with poor health? A population
      based study.
AB  - BACKGROUND: Providing informal care has been linked with poor health but has not
      previously been studied across a whole population. We aimed to study the
      association between informal care provision and self-reported poor health.
      METHOD: We used data from the UK 2001 Census. The relationship between informal
      caregiving and poor health was modelled using logistic regression, adjusting for
      age, sex, marital status, ethnicity, economic activity and educational
      attainment. RESULTS: We included 44,465,833 individuals free from permanent
      sickness or disability. 5,451,902 (12.3%) participants reported providing
      informal care to another person. There was an association between provision of
      informal caregiving and self-reported poor health; OR 1.100, 95% CI 1.096 to
      1.103. This association remained after adjustment for age, sex, ethnic group,
      marital status, economic activity and educational attainment. The association
      also increased with the amount of care provided (hours per week). CONCLUSIONS:
      Around one in eight of the UK population reports that he or she is an informal
      caregiver. This activity is associated with poor health, particularly in those
      providing over 20 h care per week.

PMID- 22875078
TI  - What types of interventions generate inequalities? Evidence from systematic
      reviews.
AB  - BACKGROUND: Some effective public health interventions may increase inequalities
      by disproportionately benefiting less disadvantaged groups ('intervention
      generated inequalities' or IGIs). There is a need to understand which types of
      interventions are likely to produce IGIs, and which can reduce inequalities.
      METHODS: We conducted a rapid overview of systematic reviews to identify evidence
      on IGIs by socioeconomic status. We included any review of non-healthcare
      interventions in high-income countries presenting data on differential
      intervention effects on any health status or health behaviour outcome. Results
      were synthesised narratively. RESULTS: The following intervention types show some
      evidence of increasing inequalities (IGIs) between socioeconomic status groups:
      media campaigns; and workplace smoking bans. However, for many intervention
      types, data on potential IGIs are lacking. By contrast, the following show some
      evidence of reducing health inequalities: structural workplace interventions;
      provision of resources; and fiscal interventions, such as tobacco pricing.
      CONCLUSION: Our findings are consistent with the idea that 'downstream'
      preventive interventions are more likely to increase health inequalities than
      'upstream' interventions. More consistent reporting of differential intervention
      effectiveness is required to help build the evidence base on IGIs.

PMID- 22875079
TI  - 5-Iodo-1,2,3-triazolium-based multidentate halogen-bond donors as activating
      reagents.
AB  - Bi- and tridentate polycationic halogen bond donors based on 5-iodo-1,2,3
      triazolium groups have been synthesized by 1,3-dipolar cycloaddition reactions.
      These halogen-based Lewis acids have been evaluated as activators in a halide
      abstraction benchmark reaction.

PMID- 22875080
TI  - Phase I trial of pomalidomide given for patients with advanced solid tumors.
AB  - PURPOSE: To determine the safety, the maximal tolerated dose, and to assess for
      any clinical activity of pomalidomide given to patients with advanced solid
      tumors. PATIENTS AND METHODS: Patients with incurable solid tumors were enrolled.
      Two different dosing schedules were explored. In Cohort A patients were given
      pomalidomide once daily for 21 days followed by a 7 day rest. For Cohort B
      additional patients were recruited to receive pomalidomide given once daily for
      28 consecutive days. Dose-limiting toxicity was defined as >=grade 3 non
      hematological toxicity that occurs during cycle 1 and that does not resolve to
      <=grade 1 by day 35. Subjects must have received optimal symptomatic treatment
      for >=grade 3 nausea, vomiting, or diarrhea to be considered a DLT. Grade 4
      transaminitis was considered to be a DLT while grade 3 transaminitis must be
      present >7 days to be a DLT. Grade 3 febrile neutropenia was considered a DLT.
      Grade 4 neutropenia, without a fever, was a DLT if the neutropenia did not
      improve to <=grade 1 by day 35 of cycle one. Platelet count <=25,000/mm(3) must
      improve to >=75,000/mm(3) by day 35 of cycle one in order not to be considered a
      DLT. If a patient did not complete one cycle of therapy, for reasons other than a
      DLT, a replacement subject was added to the same cohort level. RESULTS: A total
      of 40 patients were enrolled. In Cohort A, three patients received pomalidomide
      at 5 mg daily without any significant toxicity. Two patients in the 10 mg cohort
      experienced dose-limiting toxicities of two episodes of grade 3 dyspnea and one
      grade 4 neutropenia. Six patients were then enrolled at the 7 mg daily of
      pomalidomide, and no dose-limiting events were observed. In Cohort B, 29 patients
      were enrolled and the maximal tolerated dose was 4 mg once daily. Stable disease
      in a variety of tumors was observed. CONCLUSIONS: Pomalidomide was well tolerated
      and the recommended phase II dosing schedules are 7 mg daily given for 21 days
      followed by a 7-day rest or pomalidomide 4 mg given on an uninterrupted daily
      schedule.

PMID- 22875081
TI  - Quality of life in pediatric epilepsy: a validated questionnaire for side effects
      of AEDs.

PMID- 22875082
TI  - Development and validation of the Pediatric Epilepsy Side Effects Questionnaire.
AB  - OBJECTIVE: To develop and validate a measure of antiepileptic drug (AED) side
      effects in children with a variety of seizure types, treatments, and therapy
      durations. METHODS: Content for an initial 44-item measure was developed using
      the previously published Hague Scale and expert opinion from recognized pediatric
      epileptologists (n = 12) and caregivers of children with epilepsy (n = 21). The
      measure was completed by caregivers during routine clinic visits. Demographic and
      medical data were collected through chart reviews. Factor analysis was conducted
      and internal consistency, test-retest reliability, and construct validity were
      assessed. RESULTS: Questionnaires were analyzed from 495 children with epilepsy
      (M(age) = 10.1 years; range 2-21 years; 42% female; 14% African American; 32% new
      onset vs 68% chronic epilepsy). The final questionnaire, the Pediatric Epilepsy
      Side Effects Questionnaire (PESQ), is a 19-item measure with 5 subscales (i.e.,
      cognitive, motor, behavioral, general neurological, and weight) that accounts for
      99% of the variance. Internal consistency coefficients and test-retest
      reliabilities ranged from 0.72 to 0.93 and 0.74 to 0.97, respectively. Construct
      validity was demonstrated by increasing side effects as the number of drugs
      increased. Participants on valproic acid had significantly higher scores on the
      Weight Scale compared to those on carbamazepine. CONCLUSIONS: The PESQ is a
      reliable and valid measure of AED side effects in children across the epilepsy
      spectrum that can be used in both clinical and research settings.

PMID- 22875083
TI  - Neural anomaly and reorganization in speakers who stutter: a short-term
      intervention study.
AB  - OBJECTIVES: The aim of the current study was to differentiate between neural
      activity that represents neural anomalies that are responsible for persistent
      developmental stuttering (PDS) from the activity that is a result of compensating
      for stuttering. This was done by investigating alterations to the intrinsic
      functional architecture of speech-language processes of patients with PDS before
      and after a short-term intervention. METHODS: The resting-state functional
      connectivity (RSFC) and cortical thickness were examined before and after the
      intervention. The structural data were used to validate the functional results.
      Fifteen stuttering patients who received intervention (PDS+), 13 stuttering
      patients who did not receive intervention (PDS-), and 13 fluent controls
      participated. RESULTS: Before the intervention, both groups of PDS patients
      showed significant RSFC and cortical thickness reductions in the left pars
      opercularis (PO) and RSFC increases in the cerebellum, as compared to fluent
      controls. The intervention was effective in reducing stuttering in PDS+ patients
      and lowering their RSFC in the cerebellum to the level of fluent controls. The
      intervention effect was specific to the PDS+ group (it was not evident in the PDS
      group). The intervention did not change RSFC and cortical thickness in the left
      PO, which remained at its preintervention level. CONCLUSIONS: The results suggest
      that the left PO is a locus where the intrinsic functional architecture of speech
      language processes is altered in PDS patients, suggesting an etiologic role of
      this region in PDS. The cerebellum showed intervention-induced neural
      reorganization, suggesting a compensatory response when stuttering occurs.

PMID- 22875084
TI  - Stroke symptoms signal worse outcomes in patients with end-stage renal disease.

PMID- 22875085
TI  - Pregnancy-related hemangioblastoma progression and complications in von Hippel
      Lindau disease.
AB  - OBJECTIVE: We studied the reciprocal effect of pregnancy and von Hippel-Lindau
      (VHL) disease by analyzing the influence of pregnancy on VHL disease-related
      lesions and VHL disease on pregnancy outcome. METHODS: Medical charts and imaging
      reports from the VHL disease expertise centers in the Netherlands were used to
      retrospectively assess lesion progression score before and after pregnancy and to
      obtain data on pregnancy outcome and VHL disease-related lesions. The Friedman
      test was used for analysis (p <= 0.05). Twenty-nine patients were studied (48
      pregnancies, 49 newborns). RESULTS: The progression score of cerebellar
      hemangioblastomas significantly changed between the single MRI scan before and
      the 2 scans after pregnancy (p = 0.049) (n = 12). Fetal mortality rate was 2% (n
      = 1) caused by maternal pheochromocytoma. Maternal VHL disease-related
      complications occurred in 17% (n = 8) of all pregnancies. In 4 patients, a life
      threatening situation emerged: hydrocephalus due to cerebellar hemangioblastoma
      (n = 2) and pheochromocytoma (n = 2). CONCLUSIONS: Pregnancy in patients with VHL
      disease induces cerebellar hemangioblastoma progression and causes a high VHL
      disease-related pregnancy complication rate. We recommend intensified
      surveillance of patients with VHL disease, especially of cerebellar
      hemangioblastomas during preconception care and pregnancy.

PMID- 22875086
TI  - C9ORF72 repeat expansion in clinical and neuropathologic frontotemporal dementia
      cohorts.
AB  - OBJECTIVE: To determine the frequency of a hexanucleotide repeat expansion in
      C9ORF72, a gene of unknown function implicated in frontotemporal dementia (FTD)
      and amyotrophic lateral sclerosis (ALS), in Australian FTD patient cohorts and to
      examine the clinical and neuropathologic phenotypes associated with this
      expansion. METHODS: We examined a clinically ascertained FTD cohort (n = 89) and
      a neuropathologically ascertained cohort of frontotemporal lobar degeneration
      cases with TDP-43 pathology (FTLD-TDP) (n = 22) for the C9ORF72 hexanucleotide
      repeat expansion using a repeat primed PCR assay. All expansion-positive patients
      were genotyped for rs3849942, a surrogate marker for the chromosome 9p21 risk
      haplotype previously associated with FTD and ALS. RESULTS: The C9ORF72 repeat
      expansion was detected in 10% of patients in the clinically diagnosed cohort,
      rising to 29% in those with a positive family history of early-onset dementia or
      ALS. The prevalence of psychotic features was significantly higher in expansion
      positive cases (56% vs 14%). In the pathology cohort, 41% of TDP-43-positive
      cases harbored the repeat expansion, and all exhibited type B pathology. One of
      the 17 expansion-positive probands was homozygous for the "nonrisk" G allele of
      rs3849942. CONCLUSIONS: The C9ORF72 repeat expansion is a relatively common cause
      of FTD in Australian populations, and is especially common in those with FTD-ALS,
      psychotic features, and a strong family history. Detection of a repeat expansion
      on the 9p21 putative "nonrisk" haplotype suggests that not all mutation carriers
      are necessarily descended from a common founder and indicates that the expansion
      may have occurred on multiple haplotype backgrounds.

PMID- 22875088
TI  - Resting-state MRI: a peek through the keyhole on therapy for stuttering.

PMID- 22875087
TI  - Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features.
AB  - OBJECTIVE: To describe the phenotype of patients with C9FTD/ALS (C9ORF72)
      hexanucleotide repeat expansion. METHODS: A total of 648 patients with
      frontotemporal dementia (FTD)-related clinical diagnoses and Alzheimer disease
      (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats
      (C9+). Clinical and neuroimaging data were compared between C9+ (15 behavioral
      variant FTD [bvFTD], 11 FTD-motor neuron disease [MND], 5 amyotrophic lateral
      sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS). RESULTS:
      All C9+ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first
      evaluation, C9+ bvFTD patients had more delusions and greater impairment of
      working memory, but milder eating dysregulation compared to bvFTD noncarriers.
      C9+FTD-MND patients had a trend for longer survival and had an earlier age at
      onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more
      thalamic atrophy in FTD and FTD-MND carriers than in noncarriers. CONCLUSIONS:
      Patients with the C9ORF72 hexanucleotide repeat expansion develop bvFTD, ALS, or
      FTD-MND with similar clinical and imaging features to sporadic cases. Other FTD
      spectrum diagnoses and AD dementia appear rare or absent among C9+ individuals.
      Longer survival in C9+ FTD-MND suggests slower disease progression and thalamic
      atrophy represents a novel and unexpected feature.

PMID- 22875089
TI  - Long-term learning of stroke knowledge among children in a high-risk community.
AB  - OBJECTIVES: To evaluate the effect of Hip Hop Stroke, a school-based multimedia
      musical stroke literacy intervention that targets children aged 8-12 in high-risk
      minority communities, on the long-term learning of stroke knowledge. METHODS: We
      enrolled a cohort of 104 fifth and sixth grade children from 2 schools in Central
      Harlem into a single course of Hip Hop Stroke (3 1-hour classroom sessions,
      delivered over 3 consecutive days). Tests evaluating knowledge of stroke symptoms
      and behavioral intent to call 911 using hypothetical stroke scenarios were
      conducted at baseline, immediately after the intervention, and 15 months after
      the initial and only intervention. A composite score was created from 5
      traditional stroke symptoms plus a distracter (chest pain). Data were analyzed
      using SAS version 9.2. RESULTS: A total of 104 students completed both pretests
      (PTs) and immediate posttests (IPs), and 85 students completed all 3 tests,
      including a 15-month delayed posttest (DP) (81.7% retention rate). At pretest,
      55.8% correctly identified calling 911. The baseline composite score was 3.24 (SD
      1.45). At IP, stroke knowledge increased significantly across all items: calling
      911 (85.6%, p < 0.001) and composite score (5.30, p < 0.0001). At 15 months,
      stroke knowledge increased significantly from PT for all measures except sudden
      headache with a composite score of 4.73 (p < 0.0001, PT vs DP). CONCLUSION: Three
      hours of Hip Hop Stroke significantly improved knowledge of stroke symptoms and
      behavioral intent to call 911 of fifth and sixth grade children living in a high
      stroke risk neighborhood. This learning persisted for up to 15 months
      postintervention.

PMID- 22875090
TI  - Prevalence and significance of stroke symptoms among patients receiving
      maintenance dialysis.
AB  - OBJECTIVE: The purpose of this cross-sectional study was to determine the
      prevalence and potential significance of stroke symptoms among end-stage renal
      disease (ESRD) patients without a prior diagnosis of stroke or TIA. METHODS: We
      enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and
      functional status, basic and instrumental activities of daily living (ADL, IADL),
      were ascertained by validated questionnaires. Cognitive function was assessed
      with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs
      below norms for age and education in 2 domains. IADL impairment was defined as
      needing assistance in at least 1 of 7 IADLs. RESULTS: Among the 126 participants
      without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke
      symptoms. After adjustment for age, sex, race, education, language, diabetes, and
      cardiovascular disease, participants with stroke symptoms had lower scores on
      tests of attention, psychomotor speed, and executive function, and more
      pronounced dependence in IADLs and ADLs (p <= 0.01 for all). After adjustment for
      age, sex, race, education, language, diabetes, and cardiovascular disease,
      participants with stroke symptoms had a higher likelihood of cognitive impairment
      (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03-5.92) and IADL
      impairment (OR 3.86, 95% CI 1.60-9.28). CONCLUSIONS: Stroke symptoms are common
      among patients with ESRD and strongly associated with impairments in cognition
      and functional status. These findings suggest that clinically significant stroke
      events may go undiagnosed in this high-risk population.

PMID- 22875091
TI  - PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and
      infantile convulsions.
AB  - OBJECTIVE: To describe the phenotypes and penetrance of paroxysmal kinesigenic
      dyskinesia (PKD), a movement disorder characterized by attacks of involuntary
      movements occurring after sudden movements, infantile convulsion and
      choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions
      (BFIC), caused by PRRT2 mutations. METHODS: We performed clinical and genetic
      studies in 3 large families with ICCA, 2 smaller families with PKD, and 4
      individuals with sporadic PKD. Migraine was also present in several individuals.
      RESULTS: We detected 3 different PRRT2 heterozygous mutations: the recurrent
      p.Arg217Profs*8 mutation, previously reported, was identified in 2 families with
      ICCA, 2 families with PKD, and one individual with sporadic PKD; one novel
      missense mutation (p.Ser275Phe) was detected in the remaining family with ICCA;
      and one novel truncating mutation (p.Arg217*) was found in one individual with
      sporadic PKD. In the 2 remaining individuals with sporadic PKD, PRRT2 mutations
      were not detected. Importantly, PRRT2 mutations did not cosegregate with febrile
      convulsions or with migraine. The estimated penetrance of PRRT2 mutations was
      61%, if only the PKD phenotype was considered; however, if infantile convulsions
      were also taken into account, the penetrance was nearly complete. Considering our
      findings and those reported in literature, 23 PRRT2 mutations explain ~56% of the
      families analyzed. CONCLUSIONS: PRRT2 mutations are the major cause of PKD or
      ICCA, but they do not seem to be involved in the etiology of febrile convulsions
      and migraine. The identification of PRRT2 as a major gene for the PKD-ICCA-BFIC
      spectrum allows better disease classification, molecular confirmation of the
      clinical diagnosis, and genetic testing and counseling.

PMID- 22875092
TI  - Learning standardized sign-outs: handoff help just in time!

PMID- 22875093
TI  - Microbleeds do not affect rate of cognitive decline in Alzheimer disease.
AB  - OBJECTIVE: To investigate the relationship between brain microbleeds (MBs) and
      the rate of cognitive decline in Alzheimer disease (AD). METHODS: In this cohort
      study, we studied 221 patients with AD with available baseline MRI scans (1.0 or
      1.5 T) and at least 2 Mini-Mental State Examinations (MMSE) scores obtained more
      than 1 year apart from our memory clinic. Mean +/- SD follow-up time was 3 +/- 1
      years, and patients had a median of 4 MMSE scores (range 2-17). We used linear
      mixed models with sex and age as covariates to investigate whether MBs influenced
      the rate of cognitive decline. RESULTS: Mean age was 68 +/- 9 years, 109 (49%)
      patients were female, and the baseline MMSE score was 22 +/- 4. There were 39
      patients (18%) with MBs (median 2, range 1-27) and 182 without. Linear mixed
      models showed that overall patients declined 2 MMSE points per year. We found no
      association of the presence of MBs with baseline MMSE or change in MMSE.
      Adjustment for atrophy, white matter hyperintensities, lacunes, and vascular risk
      factors did not change the results nor did stratification for MB location, APOE
      epsilon4 carriership, or age at onset (<=65 years vs >65 years). Repeating the
      analyses with number of MBs as predictor rendered similar results. CONCLUSION:
      MBs did not influence the rate of cognitive decline in patients with AD. The
      formerly reported increased risk of mortality in patients with MBs seems not to
      be attributable to a steeper rate of decline per se but might be due to vascular
      events, including (hemorrhagic) stroke.

PMID- 22875094
TI  - FTD/ALS families are no longer orphaned: the C9ORF72 story.

PMID- 22875095
TI  - Standardized sign-out improves completeness and perceived accuracy of inpatient
      neurology handoffs.
AB  - OBJECTIVES: As residency programs adjust to new duty hour restrictions, the use
      of cross-coverage systems requiring handoffs will rise. Handoffs are vulnerable
      to communication failures when unstructured. Accordingly, we implemented a
      standardized sign-out process on our inpatient neurology services and assessed
      its effect on completeness and perceived accuracy of handoffs. METHODS: Residents
      spent the first half of their rotations utilizing unstructured sign-out. They
      transitioned to a structured sign-out system (using the situation-background
      assessment-recommendation format) during the second half of their rotations. We
      analyzed survey responses before and after implementation to evaluate for an
      effect. RESULTS: Residents utilizing structured sign-out were significantly more
      likely to share test results with patients/families prior to shift changes (p =
      0.037), update our electronic service list (p = 0.045), and feel all important
      data were being transmitted (p = 0.041). Overall satisfaction (scale 1-10)
      increased from 6.2 +/- 1.6 to 7.4 +/- 1.3 (p = 0.002). CONCLUSIONS: Our findings
      demonstrate that standardized sign-out improves the completeness and perceived
      accuracy of handoffs. Such improvement has the potential to improve patient
      safety and quality of care.

PMID- 22875097
TI  - Acute hydrocephalus due to impaired CSF resorption in Toscana virus
      meningoencephalitis.

PMID- 22875096
TI  - Chronic active varicella zoster virus infection.

PMID- 22875098
TI  - Paired associate learning in children with neurofibromatosis type 1: implications
      for clinical trials.
AB  - Studies investigating behavior in mice with a heterozygous null mutation of the
      NF1 gene (Nf1 (+/-)) have provided critical insights into the molecular and
      cellular mechanisms underlying cognitive impairments associated with
      neurofibromatosis type 1 (NF1). Hyperactivation of the Ras-MAPK signaling
      cascade, which results in increased GABA-mediated inhibition and significantly
      reduced long-term potentiation, has been proposed as a core mechanism underlying
      Nf1 (+/-) mice deficits in visuospatial learning and attention. This assertion
      has been reinforced by preclinical trials that reveal that these impairments can
      be rescued both at a cognitive and cellular level. We attempted to demonstrate a
      phenotypic parallel between Nf1 (+/-) mice and children with NF1 using a well
      validated measure of visuospatial learning. Children with NF1 (n = 71) and
      healthy controls (n = 29) were assessed on a computerized paired associate
      learning task. Interrelationships between visuospatial learning and other
      cognitive abilities that may influence performance, such as intelligence,
      attention and visuospatial function, were explored. Children with NF1 displayed
      significant impairments in visuospatial learning, with reduced initial retention
      and poorer learning across repeated trials. Importantly, we demonstrated that
      visuospatial learning was inferior in NF1 even after accounting for group
      differences in intelligence, sustained attention and visuospatial abilities. We
      have thus identified impaired visuospatial learning as a core phenotypic feature
      in children with NF1. These findings imply that hippocampal-based learning
      networks are dysfunctional in children with NF1 and provide validation for a
      primary outcome measure for clinical trials aiming to correct aberrant Ras
      signaling.

PMID- 22875099
TI  - Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the
      search of biomarkers in multiple sclerosis.
AB  - Inflammatory serum parameters are intensely investigated in the search of
      biomarkers for disease activity and treatment response in multiple sclerosis
      (MS). A reason for contradictory results might be the timing of blood collection
      for analyzing serum concentrations of inflammatory parameters which are subject
      to diurnal changes. We included 34 untreated patients with relapsing-remitting MS
      and 34 age- and sex-matched healthy controls. 12 MS patients showed acute disease
      activity in corresponding MRI scans. Blood samples were obtained at 7.00, 11.00
      am, 2.30, 6.00 and 9.30 pm within 1 day. We determined serum levels of cortisol
      and inflammatory markers including soluble tumor necrosis factor-beta (sTNF
      beta), soluble TNF-Receptor-1 (sTNF-R1) and -2 (sTNF-2), soluble vascular
      adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1
      (sICAM-1) by ELISA. We observed significantly higher serum levels of sTNF-R1 (p <
      0.001) and sTNF-R2 (p < 0.001) in the morning and a significant decline of sICAM
      1 (p < 0.005) and sVCAM-1 (p < 0.001) in the afternoon in both, MS patients and
      healthy controls. Comparison of diurnal serum levels between MS patients with
      active versus with non-active disease revealed significantly higher serum levels
      of sVCAM-1 (p < 0.05) around noon and in the early afternoon in MS patients with
      active disease. A significant decline of sICAM-1 (p < 0.05) in the afternoon was
      seen in MS patients with active and non-active disease. Our data indicate that
      increased awareness of potential diurnal serum concentration changes of
      biomarkers can eliminate one major cause of biased data as they occur in most of
      the investigated immunological parameters.

PMID- 22875101
TI  - Dendritic phosphoramidite ligands for Rh-catalyzed [2+2+2] cycloaddition
      reactions: unprecedented enhancement of enantiodiscrimination.
AB  - Phosphorus dendrimers containing terminal phosphoramidite ligands have been found
      to be highly effective and recoverable catalysts for the rhodium(I) catalyzed
      [2+2+2] cycloaddition reactions. A strong positive dendritic effect is observed
      both in the activity and enantiodiscrimination leading to axially chiral biaryl
      compounds.

PMID- 22875100
TI  - Metals, trace elements, polychlorinated biphenyls, organochlorine pesticides, and
      brominated flame retardants in tissues of Barrow's goldeneyes (Bucephala
      islandica) wintering in the St. Lawrence marine ecosystem, eastern Canada.
AB  - The eastern North American population of Barrow's goldeneyes winters in the St.
      Lawrence Estuary and Gulf of St. Lawrence where the sediments and food web are
      known to be contaminated with inorganic and organic compounds. Therefore, there
      is a potential for contamination of this population, which is designated of
      Special Concern by the Committee on the Status of Endangered Wildlife in Canada.
      Specimens were collected during three consecutive winters (2005-2007) in three
      regions (Manicouagan, Charlevoix, and Chaleur Bay) and analysed for metals, trace
      elements, polychlorinated biphenyls (PCBs), organochlorine pesticides, and
      brominated flame retardants (BFRs). Liver mercury levels were greater in the St.
      Lawrence Estuary (4.4 mg/kg in Manicouagan, 3.8 mg/kg in Charlevoix) than in
      Chaleur (2.4 mg/kg), whereas selenium showed the opposite pattern (7.3 mg/kg in
      Manicouagan, 7.0 mg/kg in Charlevoix, and 36.9 mg/kg in Chaleur). Liver PCB
      levels were greater in specimens from Manicouagan (236 ng/g) than in those from
      the two other regions (72 ng/g in Charlevoix, 35 ng/g in Chaleur). DDT was
      greater in Chaleur (66 ng/g) versus 10 ng/g in Manicouagan and 16 ng/g in
      Charlevoix. BFRs were not compared among regions because of smaller sample sizes,
      but mean total concentration was low (4.02 ng/g). Overall, although significant
      differences were found across regions, levels of all contaminants measured are
      generally low and not of toxicological concern for this population.

PMID- 22875102
TI  - CCR5 antagonism impacts vaccination response and immune profile in HIV-1
      infection.
AB  - Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target
      a host cell surface molecule, and successful HIV-1 entry blockade by this C-C
      chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We
      hypothesized that MVC intensification impacts immunization responses, T-cell
      phenotype, function and delayed type hypersensitivity (DTH) in HIV-1(+) subjects.
      A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to
      suppressive antiretroviral therapy in HIV-1(+) persons was performed. Subjects
      received DTH tests, intramuscular tetanus, meningococcal and oral cholera
      immunizations. Antibody titers, T-cell function and phenotype were assessed. Of
      157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced
      meningococcal neo-immunization, blunted cholera response and expedited
      lymphoproliferation to tetanus boost, without affecting recall humoral response.
      Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function
      improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the
      percentage of late-stage and major histocompatibility complex (MHC) class II
      expressing CD4 T-cells increased. Activated CD4(+) CD38(+) human leukocyte
      antigen (HLA)-DR(+) T-cells declined, and costimulation shifted to coinhibition.
      DTH was unchanged. Maraviroc intensification, through antagonism of the cell
      surface molecule CCR5, favorably influences immune profiles of HIV-1(+) patients,
      supporting its immunomodulatory use in HIV-1 infection and potentially in other
      immunologically relevant settings.

PMID- 22875103
TI  - Quantification of intracellular polyhydroxyalkanoates by virtue of personalized
      flow cytometry protocol.
AB  - Polyhydroxyalkanoates (PHAs) are natural polyesters produced by microbes, a
      potential alternative to synthetic plastics. Various methods ranging from
      gravimetry to spectrophotometry are routinely used for qualitative analysis of
      extracted PHA. There is a great need for accurate quantification of intracellular
      PHA during bioprocess. Hence, the present study aims to improvise the existing
      Nile red-based flow cytometry protocol. It was achieved using respective cells in
      a non-PHA accumulating state as gating control to minimize non-specific staining.
      The optimal Nile red concentration required for PHA staining is 5 * 10(3) pg mL(
      1), which is ~10(3)-fold less than that of earlier reports. Further, it was
      inferred that flow-based quantification was more accurate than the gravimetric
      method. The intracellular PHA content was highest in Pseudomonas sp. MNNG-S
      (52.06 %) among the Pseudomonas strains tested by the flow-based method. Both
      gravimetric and flow-based cell cycle analyses revealed that DNA synthesis (S
      phase) and PHA production (log phase) are synchronous at 24-48 h of culture. This
      study supports flow-based PHA quantification for real time online measurement of
      intracellular PHA for bioreactor monitoring, control and optimization enduing
      industrial applications.

PMID- 22875104
TI  - Ser-substituted mutations of Cys residues in Bacillus thuringiensis Vip3Aa7 exert
      a negative effect on its insecticidal activity.
AB  - Vegetative insecticidal proteins (VIPs), which were produced by Bacillus
      thuringiensis during its vegetative growth stage, display a broad insecticidal
      spectrum to Lepidoptera larvae. Sequence alignment of the Vip3A-type indicates
      that three cysteine residues were conserved in Vip3A-type proteins. To determine
      whether these conserved cysteine residues contributed to the insecticidal
      activity, the three residues were respectively substituted with serine in the
      Vip3Aa7 protein by site-directed mutagenesis. Bioassays using the third instar
      larvae of Plutella xylostella showed that the toxicity of C401S and C507S mutants
      were completely abolished. To find out the inactivity reason of mutants, three
      mutants and the wild-type Vip3Aa7 were treated with trypsin. The results
      indicated that the C507S mutant was rapidly cleaved and resulted in decrease of
      the 62 kDa toxic core fragment. These results indicated that the replacement of
      the Cys(507) with a Ser(507) caused decrease in C507S resistance against trypsin
      degradation. It is suggesting a possible association between insecticidal
      activity and trypsin sensitivity of Vip3A proteins. This study serves a guideline
      for the study of Vip3A protein structure and active mechanism.

PMID- 22875105
TI  - Where does the author belong?

PMID- 22875106
TI  - The doctor as an administrator  of legislative rules.

PMID- 22875111
TI  - [Theme: Spinal cord injuries].

PMID- 22875113
TI  - [Thiazides is still well-founded treatment].

PMID- 22875115
TI  - [The sick mother].

PMID- 22875116
TI  - [False grounds for dismissal].

PMID- 22875118
TI  - [Is early ultrasonography good for everyone?].

PMID- 22875119
TI  - [Do physicians have appropriately distributed work time?].

PMID- 22875120
TI  - [Hearing impaired among the hearing].

PMID- 22875121
TI  - [Possible delayed effects in dental personnel from mercury exposure].

PMID- 22875122
TI  - [Organization of emergency medicine--it is urgent!].

PMID- 22875123
TI  - Are the Norwegian guidelines  for ultrasound in prenatal diagnosis followed?
AB  - BACKGROUND: The Norwegian Biotechnology Act distinguishes between ultrasound as
      part of routine antenatal care and fetal diagnostic ultrasound. The Act is
      criticised for being unclear and difficult to comply with in clinical practice.
      The purpose of this study was to investigate whether doctors complied with the
      guidelines in the Biotechnology Act when they considered the case histories of
      women who wanted early ultrasound with fetal diagnosis. MATERIAL AND METHOD: We
      asked gynaecologists in private practice, experts in fetal medicine and lawyers
      and consultants in the Department of Biotechnology and Health Law at the
      Norwegian Directorate of Health to evaluate six hypothetical cases of women who
      wanted early ultrasound. RESULTS: We received responses from 64 of 139 (49 %) of
      private gynaecologists, 22 of 27 (81 %) of doctors at fetal medicine centres and
      5 of 12 (42 %) respondents at the Directorate of Health. Only 29 of 86 (34 %) of
      the doctors responded that they strictly comply with the age criterion of 38
      years. 33 of 64 /52 %) of private gynaecologists would measure nuchal
      translucency themselves, and 43 of 64 (67 %) have referred patients for fetal
      diagnosis on the indication of "anxiety". 16 of 22 (73 %) of doctors at fetal
      medicine centres were of the view that anxiety is an indication for fetal
      diagnostics. All respondents at the Directorate of Health responded that this is
      not correct according to the guidelines. INTERPRETATION: The majority of doctors
      did not strictly comply with the guidelines when they evaluated the case
      histories, and the guidelines were interpreted differently by doctors and
      respondents at the Directorate of Health.

PMID- 22875124
TI  - Hospitalisations due  to exacerbation of asthma and COPD.
AB  - BACKGROUND: Patients with exacerbation of asthma and COPD often need instant
      treatment, and acute hospitalisation may be necessary. The aim of the study was
      to determine what sort of contact patients had with doctors, and what sort of
      treatment they received immediately prior to hospitalisation due to exacerbation.
      MATERIAL AND METHOD: A questionnaire was distributed to patients aged over 18 who
      were hospitalised because of asthma or COPD exacerbation in Helgeland Hospital
      and the University Hospital of North Norway, Tromso, between January 2010 and
      January 2011. The patients answered questions on the duration of the
      exacerbation, their contact with doctors and their medical treatment prior to
      hospitalisation. RESULTS: Data received from 100 of the 122 patients were
      analysed. The median duration of illness prior to the first contact with a doctor
      was four days. 52 of the patients had contacted their primary doctor first, 40
      contacted A&E first, while eight contacted the hospital directly. The first
      contact with a doctor resulted in the hospitalisation of 56 patients: 21 (40 %)
      of those who contacted their primary doctor and 26 (70 %) of those who contacted
      A&E. 41 patients were hospitalised without being clinically examined by the
      admitting doctor the same day, 32 after a telephone consultation with their
      primary doctor or an A&E doctor. Patients aged over 70 were more frequently
      admitted without a clinical examination, as were patients who had been
      hospitalised previously. INTERPRETATION: Patients with asthma or COPD
      exacerbation are often hospitalised directly after a telephone consultation with
      their primary doctor or an A&E doctor.

PMID- 22875125
TI  - [Juvenile myoclonic epilepsy].
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME) is a generalised epilepsy with
      seizure onset in youth. The aim of this review is to present updated knowledge
      about the etiology, diagnosis and treatment of JME. MATERIAL AND METHOD: The
      review is based on a judicious selection of original English language articles,
      meta-analyses, and reviews found in PubMed, and the authors' own experience with
      the patient group. RESULTS: Seizure onset occurs in adolescence. All have
      myoclonias, about 90 % have generalized tonic-clonic seizures, and one third have
      absences. Myoclonic jerks are frequently the debut symptom, while tonic-clonic
      seizures appear later on. Patients are particularly susceptible to seizures
      shortly after waking. It is important to ask specifically about myoclonias as
      most patients do not report jerks spontaneously. The electroencephalograms of 44
      81 % of the patients show discharges of 4-6 Hz polyspike waves. Focal EEG
      abnormalities may be seen in about 30 %. When patients are treated with valproate
      and seizure-precipitating factors are avoided, especially sleep deprivation,
      about 80 % become seizure-free. Lamotrigine and levetiracetam are alternative
      therapies for women of childbearing age. Attempts to taper off the medication
      after several years of seizure freedom entail a high risk of seizure relapse.
      INTERPRETATION: As there may be features of focal epilepsy in the seizure
      semiology and/or the EEGs, it may be difficult to diagnose JME. Thus, many
      patients are misdiagnosed as having a focal epilepsy and are given antiepileptic
      drugs that may aggravate the tendency to seizures.

PMID- 22875126
TI  - [Epilepsy surgery--assessment and patient selection].
AB  - BACKGROUND: Considerable progress in diagnostic imaging and video EEG monitoring
      has improved the possibilities of localising the epileptogenic zone of the brain
      in patients with epilepsy. Despite the fact that epilepsy surgery can therefore
      be offered to more patients today than previously, relatively few patients are
      referred for an assessment for surgery. The aim of this review is to provide a
      brief account of the patient selection procedures and the investigations prior to
      epilepsy surgery. METHOD: The review is based on a literature search in PubMed
      and the personal experiences of the authors in this field. RESULTS: If the
      epilepsy does not respond to any kind of pharmacological treatment, and
      idiopathic generalised epilepsy and pseudoresistance have been ruled out, the
      patient should be evaluated for surgery. The evaluation is multidisciplinary, and
      the aim is to localise the epileptogenic zone, which can be identified by both
      structural and functional abnormalities. It must be determined before the
      operation whether the zone can be removed without leaving severe neurological or
      cognitive impairment. The best results after epilepsy surgery are seen in
      patients with a morphological substrate, particularly temporal lobe epilepsy
      associated with hippocampal sclerosis. INTERPRETATION: Epilepsy surgery plays an
      ever more important role in the treatment of patients with drug resistant
      seizures. Doctors who treat epileptic patients should refer candidates for
      surgery at an early stage of the disease.

PMID- 22875127
TI  - [Quetiapine and the potential for abuse].
AB  - Quetiapine is an atypical antipsychotic licensed for the treatment  of
      schizophrenia and bipolar disorder and as an adjunctive for patients  with
      unipolar depression. Case reports suggest a potential for drug  abuse, especially
      among individuals with prior or current abuse  of other substances.

PMID- 22875128
TI  - [A man in his fifties with fever, cough and anuria].

PMID- 22875129
TI  - [Serious illness--tough treatment].

PMID- 22875130
TI  - [Young man with severe back pain].

PMID- 22875131
TI  - [When should bisphosphonate treatment be discontinued?].

PMID- 22875132
TI  - [The difficult word inform].

PMID- 22875133
TI  - [Benefits when children are ill--more trouble than support?].

PMID- 22875135
TI  - Isolation of an aerobic sulfur oxidizer from the SUP05/Arctic96BD-19 clade.
AB  - Bacteria from the uncultured SUP05/Arctic96BD-19 clade of gamma proteobacterial
      sulfur oxidizers (GSOs) have the genetic potential to oxidize reduced sulfur and
      fix carbon in the tissues of clams and mussels, in oxygen minimum zones and
      throughout the deep ocean (>200 m). Here, we report isolation of the first
      cultured representative from this GSO clade. Closely related cultures were
      obtained from surface waters in Puget Sound and from the deep chlorophyll maximum
      in the North Pacific gyre. Pure cultures grow aerobically on natural seawater
      media, oxidize sulfur, and reach higher final cell densities when glucose and
      thiosulfate are added to the media. This suggests that aerobic sulfur oxidation
      enhances organic carbon utilization in the oceans. The first isolate from the
      SUP05/Arctic96BD-19 clade was given the provisional taxonomic assignment
      'Candidatus: Thioglobus singularis', alluding to the clade's known role in sulfur
      oxidation and the isolate's planktonic lifestyle.

PMID- 22875136
TI  - Assessment of retinal layers and visual rehabilitation after epiretinal membrane
      removal.
AB  - BACKGROUND: To evaluate the changes in visual acuity, metamorphopsia, and
      thickness of retinal layers after epiretinal membrane (ERM) removal and to
      investigate factors associated with visual function. METHODS: This prospective
      study included 52 eyes of 52 patients who underwent surgery for idiopathic ERM.
      Changes in visual acuity, metamorphopsia score (M-score) using M-chart, and
      parafoveal thickness of each retinal layer were evaluated preoperatively and at 2
      month and 6-month postoperative follow-up visits. Factors associated with visual
      acuity and M-score were investigated. RESULTS: Although continuous improvement in
      visual acuity and decrease in the thickness of parafoveal retinal layers
      following ERM removal was observed, relatively slow improvement in M-score was
      noted with values of 0.32 +/- 0.27, 0.44 +/- 0.46, and 0.23 +/- 0.23,
      respectively at the defined time points. A preoperative increase in the thickness
      of parafoveal retina was mainly caused by increased thickness of inner retinal
      layers. Preoperative thickness of inner nuclear layer (INL) were closely
      associated with preoperative, postoperative visual acuity, and preoperative M
      score (p = 0.001, 0.012, and 0.027, respectively). CONCLUSIONS: Compared with the
      postoperative improvement in visual acuity, the postoperative improvement in
      metamorphopsia was a rather slow process. Parafoveal INL thickness was found to
      be a significant structural factor for visual acuity and metamorphopsia in ERM.

PMID- 22875137
TI  - A hexanuclear gadolinium-organic octahedron as a sensitive MRI contrast agent for
      selectively imaging glucosamine in aqueous media.
AB  - A hexanuclear gadolinium octahedral nanocage was self-assembled as an efficient
      multimeric magnetic resonance probe for selectively responding glucosamine. The
      rigid facial bridging ligands provided additional enhancements for the proton
      relativity around gadolinium ions, ensuring the application of MRI in vivo.

PMID- 22875138
TI  - The relationship between pediatric nonalcoholic fatty liver disease and
      cardiovascular risk factors and increased risk of atherosclerosis in obese
      children.
AB  - To investigate the relationship between nonalcoholic fatty liver disease and
      cardiovascular risk factors and increased risk of atherosclerosis in obese
      children. The study included 80 consecutive obese children who were stratified
      into group 1 [ultrasonographically diagnosed with NAFLD (n = 50)] and group 2
      [not diagnosed with NAFLD (n = 30)]. The control group included 30 healthy
      children. The groups were compared in terms of clinical cardiovascular risk
      factors and carotid intimal medial thickness (CIMT) (as a marker of
      atherosclerosis) measured using B-mode ultrasound. Mean body mass index (BMI) and
      blood pressure (BP), as well as the frequency of dyslipidemia, metabolic syndrome
      (MetS), and insulin resistance (IR), were similar in groups 1 and 2. Mean BMI and
      triglyceride (TG) levels, and the frequency of IR and MetS, increased
      significantly as the grade of steatosis increased. Mean CIMT in group 1 was
      significantly greater than that in the control group (P < 0.01). There was a
      positive correlation between CIMT and age, BP, and BMI in groups 1 and 2. In
      addition, CIMT was correlated with TG, low high-density lipoprotein (HDL)
      cholesterol, MetS, and IR only in group 1. Linear regression analysis between
      CIMT and age, BP, BMI, TG level, HDL cholesterol level, IR, MetS, and grade of
      steatosis yielded a significant difference only for grade of steatosis.
      Cardiovascular risk factors are more impressive and CIMT was significantly higher
      in group 1 than in group 2 and the control group, indicating that they are
      associated with greater risk of atherosclerosis and future adverse cardiovascular
      events.

PMID- 22875139
TI  - Isolated total anomalous systemic venous drainage in an adult: case report.
AB  - Total anomalous systemic venous drainage is a rare form of congenital heart
      disease. All the systemic venous flow from the body (i.e., from the superior vena
      cava, inferior vena cava, and coronary sinus) drains abnormally into the left
      atrium. This condition requires the presence of a left-to-right shunt (atrial
      septal defect, patent ductus arteriosus, or ventricular septal defect) to allow
      the systemic venous return to reach the pulmonary circulation. This disorder may
      be associated with heterotaxy syndromes. This report describes a patient with
      unique total anomalous systemic venous drainage that was successfully corrected
      surgically. 

PMID- 22875140
TI  - Effect of ventriculotomy on right-ventricular remodeling in hypoplastic left
      heart syndrome: a histopathological and echocardiography correlation study.
AB  - The objective of this study was to compare histopathological changes in
      hypoplastic left heart syndrome right ventricles (RV) of patients undergoing Sano
      and modified Blalock-Taussig (MBT) shunt and correlate them with
      echocardiographic findings. Myocardial tissue samples were obtained from hearts
      with Sano or MBT shunts after transplantation or at autopsy. Histologic sections
      were reviewed manually and by automated digital image analysis. Velocity vector
      imaging was performed on echocardiogram images obtained before transplant or
      death. All of these parameters were compared between the Sano and MBT shunt
      cohorts. A total of 14 specimens (7 Sano and 7 MBT shunt) were studied. Median
      age at transplant/death of Sano and MBT shunt cohorts was 11 (range 2-41) and 8
      months (range 2-200), respectively. All Sano specimens had a scar at
      ventriculotomy site, and the mean scar area was 6.2 +/- 3.3 cm(2). Compared with
      remote RV free wall, myocardium bordering the scar showed increased fibrosis (34
      +/- 16 % vs. 28 +/- 14 %, p = 0.04) and thinning (0.8 +/- 0.9 vs. 5.3 +/- 0.8 mm;
      p < 0.001), which did not regress with time. The Sano ventriculotomy site showed
      significantly decreased velocity, strain, and strain rate compared with the
      corresponding contralateral segment. No focal scarring or regional hypokinesia
      was seen in the MBT shunt cohort. This is the first study to demonstrate
      histopathological features of ventriculotomy-associated RV myocardial scarring
      and myocardial thinning. The scarred ventriculotomy site showed decreased
      segmental myocardial deformation after Norwood with Sano shunt.

PMID- 22875141
TI  - Effecting change in primary care management of respiratory  conditions: a global
      scoping exercise and literature review of  educational interventions to inform
      the IPCRG's E-Quality  initiative.
AB  - This discussion paper describes a scoping exercise and literature review
      commissioned by the International Primary Care Respiratory Group  (IPCRG) to
      inform their E-Quality programme which seeks to support small-scale educational
      projects to improve respiratory management  in primary care. Our narrative review
      synthesises information from three sources: publications concerning the global
      context and health  systems development; a literature search of Medline, CINAHL
      and Cochrane databases; and a series of eight interviews conducted with  members
      of the IPCRG faculty. Educational interventions sit within complex healthcare,
      economic, and policy contexts. It is essential that any  development project
      considers the local circumstances in terms of economic resources, political
      circumstances, organisation and administrative  capacities, as well as the
      specific quality issue to be addressed. There is limited evidence (in terms of
      changed clinician behaviour and/or  improved health outcomes) regarding the
      merits of different educational and quality improvement approaches. Features of
      educational  interventions that were most likely to show some evidence of
      effectiveness included being carefully designed, multifaceted, engaged health 
      professionals in their learning, provided ongoing support, were sensitive to
      local circumstances, and delivered in combination with other quality  improvement
      strategies. To be effective, educational interventions must consider the complex
      healthcare systems within which they operate.  The criteria for the IPCRG E
      Quality awards thus require applicants not only to describe their proposed
      educational initiative but also to consider  the practical and local barriers to
      successful implementation, and to propose a robust evaluation in terms of changed
      clinician behaviour or  improved health outcomes.

PMID- 22875142
TI  - Strategies for living with the risk of anaphylaxis in  adolescence: qualitative
      study of young people and their  parents.
AB  - BACKGROUND: Adolescents with anaphylaxis are at increased risk of fatal outcomes.
      Gaps in their knowledge of day-to-day and  emergency management have been
      identified. There are also gaps in services available to support adolescents at
      risk of anaphylaxis. AIMS: To explore the experiences and healthcare needs of
      adolescents living with the risk of anaphylaxis; to understand the perspectives 
      of their parents; and to look at how care might be improved. METHODS: A
      qualitative study was undertaken using in-depth interviews with adolescents with
      a recent history of severe allergic reactions  and with their parents. RESULTS:
      Twenty-six adolescents at risk of anaphylaxis living in Scotland and their
      parents (n=28) were recruited. Most anaphylactic reactions  reported by
      participants appeared to result from accidents, misinformation, or inexperience.
      For many, management involved finding a balance  between taking their allergies
      seriously whilst not allowing these concerns to dominate their lives. Risks were
      often difficult to judge, with  reactions sometimes taking place even after
      careful checking of meal ingredients. Most admitted taking some risks with trace
      labelled foods.  Appropriate healthcare support for adolescents in learning to
      manage the risk of anaphylaxis independently and advice and support for their 
      parents was inconsistently provided. CONCLUSIONS: Adolescents tend to see their
      risk management strategies as 'good enough', but these strategies were often
      inconsistent with  clinical best practice and, in some cases, had not prevented
      reactions. Building on adolescents' existing skills and knowledge and the use of 
      Internet and associated social media resources may help to support more effective
      self-management among adolescents.

PMID- 22875143
TI  - Continuity, but at what cost? The impact of telemonitoring  COPD on continuities
      of care: a qualitative study.
AB  - BACKGROUND: Continuity of care is widely regarded as an important marker of
      quality in the management of patients with long-term  conditions. New services
      that integrate telemonitoring into care pathways have potential to change aspects
      of continuity in both positive  and negative ways. AIMS: A telemonitoring service
      for patients with chronic obstructive pulmonary disease (COPD) was introduced in
      Lothian, Scotland, in  2009. A qualitative study, nested within the TELESCOT COPD
      randomised control trial, was undertaken to explore the views of patients  and
      professionals on telemonitoring. The perceived impact of telemonitoring on
      continuity of care was investigated as part of the  research. METHODS: Semi
      structured interviews were undertaken with 38 patients (47% male, mean age 67.5
      years). A maximum variation sample  in relation to age, sex, socio-economic
      background, disease severity, and compliance with telemonitoring was recruited.
      Thirty-two  stakeholders (healthcare professionals and managers) were
      interviewed. Transcribed coded data were analysed thematically using the 
      framework approach. Interpretation was supported by multidisciplinary discussion.
      RESULTS: Patients and healthcare professionals considered that relationship-based
      continuity of care was important in the delivery of  telemonitoring services.
      Managers placed emphasis on improved continuity of clinical management as a means
      of reducing healthcare costs.  However, professionals described many operational
      challenges arising from the 'bolting-on' of telemonitoring provision to existing
      usual care  provision which, they considered, resulted in the proliferation of
      additional managerial discontinuities. CONCLUSIONS: Managers and healthcare
      professionals face major challenges in meeting demands for both relationship
      continuity and continuity  of clinical management in the development of
      telemonitoring services.

PMID- 22875144
TI  - Prevalence of common chronic respiratory diseases in drug  misusers: a cohort
      study.
AB  - BACKGROUND: A randomised controlled trial of substance misuse indicated that many
      patients who use methadone have respiratory symptoms and/or are prescribed
      respiratory medications. There is little research in this area. AIMS: To
      determine the prevalence of respiratory disease and prescriptions among drug
      misusers. METHODS: This historical cohort study of drug misusers and matched
      controls analysed routinely collected primary care data. The prevalence of common
      chronic respiratory diseases, class and number of respiratory medications were
      examined. RESULTS: The cohort of 18,570 patients (9,285 per group) was mostly
      male (64%, n=11,890) and aged 31-59 years (76%, n=14,060). After adjusting for
      age, gender, deprivation and smoking status, the results showed that more drug
      misusers than controls had a diagnosis of asthma or chronic obstructive pulmonary
      disease (17.1% vs. 10.9%; adjusted odds ratio (OR) 1.61, 95% confidence interval
      (CI) 1.46 to 1.77, and 2.4% vs. 0.8%; OR 1.86, 95% CI 1.42 to 2.44, respectively)
      and were prescribed more chronic respiratory medications: short-acting beta(2)
      agonists (16.4% vs. 7.9%; OR 2.00, 95% CI 1.80 to 2.22), long-acting beta(2)
      agonists (1% vs. 0.4%; OR 1.93, 95% CI 1.29 to 2.89), and inhaled corticosteroids
      (10.6% vs. 7.6%; OR 1.49, 95% CI 1.33 to 1.67). All differences were
      statistically significant (p<0.001). CONCLUSIONS: Drug misusers have a
      significantly higher prevalence of respiratory diseases and respiratory
      prescriptions than matched controls. Further work is needed to determine the
      reasons for this.

PMID- 22875145
TI  - Identifiability and inference of non-parametric rates-across-sites models on
      large-scale phylogenies.
AB  - Mutation rate variation across loci is well known to cause difficulties, notably
      identifiability issues, in the reconstruction of evolutionary trees from
      molecular sequences. Here we introduce a new approach for estimating general
      rates-across-sites models. Our results imply, in particular, that large
      phylogenies are typically identifiable under rate variation. We also derive
      sequence-length requirements for high-probability reconstruction. Our main
      contribution is a novel algorithm that clusters sites according to their mutation
      rate. Following this site clustering step, standard reconstruction techniques can
      be used to recover the phylogeny. Our results rely on a basic insight: that, for
      large trees, certain site statistics experience concentration-of-measure
      phenomena. 

PMID- 22875146
TI  - A commentary on 'TECTA mutations in Japanese with mid-frequency hearing loss
      affected by Zona Pellucida domain protein secretion'.

PMID- 22875148
TI  - Coordination of a chiral tin(II) cation bearing a bis(oxazoline) ligand with
      tetrahydrofuran derivatives.
AB  - The reaction of SnCl(2) with the lithio derivative of a bis(oxazoline) ligand
      precursor afforded the enantiomeric chlorostannylene whose chloride ion can be
      substituted by several neutral or anionic Lewis donors. Abstraction of the
      chloride ion from the chlorostannylene with silver salts gave the corresponding
      tetrahydrofuran (THF) complexes of a chiral tin(ii) cation in 1,2-dimethoxyethane
      (DME) containing THF. That is, the reaction with silver hexafluoroantimonate
      (AgSbF(6)) afforded the THF complex without interaction with the counteranion. In
      contrast, reaction with silver triflate (AgOTf) gave the THF complex whose tin
      center had a pseudo-trigonal bipyramidal structure with two nitrogen atoms of a
      bidentate ligand and a lone pair at the equatorial positions and one of the
      oxygen atoms of triflate and an oxygen atom of THF at the apical positions in the
      solid state. Use of 3-methyltetrahydrofuran (3-MeTHF) instead of THF afforded the
      3-MeTHF complexes, where the R-enantiomer of 3-MeTHF predominantly coordinates to
      the tin center. The previously reported germanium(II) analogue of the tin(II)
      cation indicated a similar enantioselectivity for the coordination of 3-MeTHF on
      the germanium center.

PMID- 22875147
TI  - Role of rare variants in undetermined multiple adenomatous polyposis and early
      onset colorectal cancer.
AB  - Some 15-20% of multiple adenomatous polyposis have no genetic explanation and 20
      30% of colorectal cancer (CRC) cases are thought to be due to inherited
      multifactorial causes. Accumulation of deleterious effects of low-frequency
      dominant and independently acting variants may be a partial explanation for such
      patients. The aim of this study was to type a selection of rare and low-frequency
      variants (<5%) to elucidate their role in CRC susceptibility. A total of 1181
      subjects were included (866 controls; 315 cases). Cases comprised UK (n=184) and
      French (n=131) patients with MAP (n=187) or early-onset CRC (n=128). Seventy
      variants in 17 genes were examined in cases and controls. The effect of the
      variant effect on protein function was investigated in silico. Out of the 70
      variants typed, 36 (51%) were tested for association. Twenty-one variants were
      rare (minor allele frequency (MAF) <1%). Four rare variants were found to have a
      significantly higher MAF in cases (EXO1-12, MLH1-1, CTNNB1-1 and BRCA2-37,
      P<0.05) than in controls. Pooling all rare variants with a MAF <0.5% showed an
      excess risk in cases (odds ratio=3.2; 95% confidence interval=1.1-9.5; P=0.04).
      Rare variants are important risk factors in CRC and, as such, should be
      systematically assayed alongside common variation in the search for the genetic
      basis of complex diseases.

PMID- 22875149
TI  - Warming and the dependence of limber pine (Pinus flexilis) establishment on
      summer soil moisture within and above its current elevation range.
AB  - Continued changes in climate are projected to alter the geographic distributions
      of plant species, in part by affecting where individuals can establish from seed.
      We tested the hypothesis that warming promotes uphill redistribution of subalpine
      tree populations by reducing cold limitation at high elevation and enhancing
      drought stress at low elevation. We seeded limber pine (Pinus flexilis) into
      plots with combinations of infrared heating and water addition treatments, at
      sites positioned in lower subalpine forest, the treeline ecotone, and alpine
      tundra. In 2010, first-year seedlings were assessed for physiological performance
      and survival over the snow-free growing season. Seedlings emerged in midsummer,
      about 5-8 weeks after snowmelt. Low temperature was not observed to limit
      seedling photosynthesis or respiration between emergence and October, and thus
      experimental warming did not appear to reduce cold limitation at high elevation.
      Instead, gas exchange and water potential from all sites indicated a prevailing
      effect of summer moisture stress on photosynthesis and carbon balance. Infrared
      heaters raised soil growing degree days (base 5  degrees C, p < 0.001) and August
      September mean soil temperature (p < 0.001). Despite marked differences in
      vegetation cover and meteorological conditions across sites, volumetric soil
      moisture content (theta) at 5-10 cm below 0.16 and 0.08 m(3) m(-3) consistently
      corresponded with moderate and severe indications of drought stress in midday
      stem water potential, stomatal conductance, photosynthesis, and respiration.
      Seedling survival was greater in watered plots than in heated plots (p = 0.01),
      and negatively related to soil growing degree days and duration of exposure to
      theta < 0.08 m(3) m(-3) in a stepwise linear regression model (p < 0.0001). We
      concluded that seasonal moisture stress and high soil surface temperature imposed
      a strong limitation to limber pine seedling establishment across a broad
      elevation gradient, including at treeline, and that these limitations are likely
      to be enhanced by further climate warming.

PMID- 22875150
TI  - Number and frequency of physiotherapy services for motor vehicle-induced
      whiplash: interrogating motor accident insurance data 2006-2009.
AB  - OBJECTIVE: Whilst prognostic factors for recovery from whiplash associated
      disorders have been documented, factors related to high physiotherapy use are not
      well recognized. This study profiles predictors for high use of physiotherapy
      services from a large dataset from an Australian state insurer for motor vehicle
      accidents. METHOD: A dataset of Motor Accident Commission claims in South
      Australia for whiplash associated disorders (2006-2009) was interrogated.
      RESULTS: The median number of physiotherapy services per claimant was 15 (range:
      1-194). The typical high user of physiotherapy was female, aged 25-59 years,
      living in a high socio-economic area, with legal representation, who delayed
      obtaining physiotherapy for at least 28 days after the accident. The largest mean
      number of days between treatments (5.4 days) in the first 5 treatments related to
      the lowest subsequent use of physiotherapy services. CONCLUSION: This represents
      the first review of physio-therapy service use based on an insurance dataset. A
      range of factors were related to high use of physiotherapy services. It is hoped
      that identifying the mean number and spread of physiotherapy interventions for
      whiplash associated disorders, and the profile of high users of physiotherapy
      will help gauge the success of strategies to maximize the efficacy of
      physiotherapy management of whiplash associated disorders.

PMID- 22875151
TI  - Assessment of health-related quality of life in patients with myasthenia gravis
      in Belgrade (Serbia).
AB  - The aim of this study was to assess factors that might influence the health
      related quality of life (HRQoL) in patients with myasthenia gravis (MG). A cross
      sectional study was performed including 230 consecutive patients with MG.
      Severity of the disease was estimated according to the MGFA classification and
      QMG score. HRQoL was assessed by the SF-36 questionnaire. Depressive and anxiety
      symptoms were assessed using the Hamilton rating scales for depression and
      anxiety, respectively. Social support was measured by the Multidimensional Scale
      of Perceived Social Support (MSPSS), and acceptance of the disease by the
      Acceptance of Illness Scale. The significant demographic predictors of worse
      HRQoL in MG patients were older age (p = 0.025) and lower education (p = 0.012).
      Among clinical features, significant independent contributing factors of worse
      HRQoL were more severe form of the disease according to MGFA (p = 0.001) and
      higher QMG score (p = 0.001). Finally, psychosocial predictors of worse quality
      of life were lower MSPSS score (p = 0.001), poor acceptance of the disease (p =
      0.001), as well as higher levels of anxiety and depression (p = 0.001). Our study
      revealed that the HRQoL in patients with MG is similarly reduced in its
      psychological and physical aspects. These results may have a practical
      implication pointing out that different aspects of psychosocial support should be
      added to the regular therapeutic protocols.

PMID- 22875152
TI  - Postfixation detergent treatment liberates the membrane modelling protein
      Pex11beta from peroxisomal membranes.
AB  - Pex11 proteins are involved in membrane remodelling processes of peroxisomes, and
      are key components of peroxisomal division and proliferation. In mammals, three
      Pex11 isoforms, Pex11alpha, Pex11beta, and Pex11gamma exist. Here we demonstrate
      that Pex11beta, but not Pex11alpha or Pex11gamma, is almost exclusively extracted
      from peroxisomal membranes of paraformaldehyde-fixed cells by permeabilisation
      with the non-ionic detergent Triton X-100. This results in diminished detection
      of Myc-Pex11beta in immunofluorescence preparations and appearance of the protein
      in the Triton X-100 extract. To our knowledge, Pex11beta is the first peroxisomal
      membrane protein showing such a peculiar behaviour. Loss of Pex11beta can be
      avoided by permeabilisation with digitonin, the addition of glutaraldehyde to the
      fixative, or the expression of a Pex11 fusion protein with a larger protein tag
      (e.g. YFP). Our observations further point to different functions and biochemical
      properties of the Pex11 isoforms within the peroxisomal membrane and during
      peroxisome proliferation.

PMID- 22875157
TI  - Capacity of peroxyl radical scavenging and inhibition of lipid peroxidation by
      beta-carotene, lycopene, and commercial tomato juice.
AB  - Carotenoids have received much attention as natural antioxidants. The role and
      action of carotenoids as singlet oxygen quenchers have been well demonstrated.
      The radical scavenging is another function of carotenoids as antioxidants, but
      the method to assess the radical scavenging capacity has not been established and
      previous studies have given inconsistent results. Carotenoids have strong
      absorptions in the visible light region and, unlike phenolic antioxidants, they
      do not have a reactive hydrogen to donate to radicals, which make it difficult to
      use conventional probes for the assessment of their radical scavenging capacity.
      In the present study, a method for the assessment of peroxyl radical scavenging
      capacity by carotenoids was re-examined and applied for beta-carotene, lycopene,
      and commercial tomato juice. The capacity for scavenging peroxyl radicals was
      assessed from the effect of alpha-tocopherol on the bleaching of carotenoids
      being tested. Total content of carotenoids was also assessed from the rate of
      bleaching under constant flux of peroxyl radicals. The peroxyl radical scavenging
      capacity of beta-carotene and lycopene exhibited was about one-tenth of that
      observed for alpha-tocopherol, and the efficacy of lipid peroxidation inhibition
      was much smaller.

PMID- 22875159
TI  - A relic from the past?

PMID- 22875158
TI  - Apparent diffusion coefficient obtained by magnetic resonance imaging as a
      prognostic marker in glioblastomas: correlation with MGMT promoter methylation
      status.
AB  - OBJECTIVE: To evaluate whether apparent diffusion coefficient (ADC) values can
      predict the status of MGMT of glioblastoma multiforme (GBM) and correlate with
      overall survival (OS) and progression-free survival (PFS). METHODS: This
      retrospective study included 47 patients with pathologically proven glioblastoma.
      All of them underwent MR DWI study before surgery (mean time 1 week) and the
      status of methylguanine-DNA-methyltransferase (MGMT) promoter methylation was
      searched for. Minimum apparent diffusion coefficient (ADC) values were evaluated.
      OS and PSF parameters were calculated, and Student's t-test, Kaplan-Meier curves,
      linear and Cox regression were performed. RESULTS: Twenty-five patients showed
      positive methylation of the MGMT promoter. Patients showing MGMT promoter
      methylation had higher minimum ADC values, and they survived longer than those
      without MGMT promoter methylation. The median ADCmin value of 0.80 represents the
      cutoff value able to distinguish between methylated and un-methylated patients.
      Patients showing minimum ADC values higher than 0.80 survived longer than
      patients with minimum ADC values lower than 0.80. A linear correlation between
      minimum ADC values vs. the OS and PFS was observed. CONCLUSIONS: Minimum ADC
      values in glioblastoma multiforme could be used as a preoperative parameter to
      estimate the status of MGMT promoter methylation and the survival of patients.

PMID- 22875160
TI  - Self-management for people with long-term neurological conditions.
AB  - Although English government policy has encouraged the implementation of self
      management programmes in services for people with long-term conditions, the
      evidence for their efficacy has been limited. People with long-term neurological
      conditions use community-based health services including community nursing, and
      have particular needs in regards to self-management. This article provides an
      overview of the evidence for the effectiveness of self-management interventions
      for people with long-term neurological conditions, in particular those with
      stroke, Parkinson's disease and multiple sclerosis. The current need for better
      interventions is highlighted, particularly the importance of providing condition
      specific information and deliverance of interventions in a group setting to
      improve self-management outcomes. In response to weaknesses of previous self
      management interventions for this population, an innovative Hertfordshire
      Neurological Service self-management programme is discussed, and the implications
      for future research are described.

PMID- 22875161
TI  - Subcutaneous injections: preventing needlestick injuries in the community.
AB  - Community nurses provide care to patients in a variety of settings, for example
      health centres, community hospitals, patients' homes, residential and nursing
      homes. Administering subcutaneous injections to patients in the community is an
      everyday activity for many nurses in clinical practice. Many problems related to
      being 'sharps safe' are common to both community nurses and hospital staff. The
      majority of subcutaneous injections administered in the community are for
      patients with diabetes. Reducing needlestick injuries after the administration of
      subcutaneous injections in the community remains paramount to all NHS staff. This
      article provides information on what national standards to employ when
      administrating subcutaneous injections and what safety practices should be
      undertaken for good sharps management. Staff administering subcutaneous
      injections in the community need to ensure that they are updated on the latest
      developments in safety needle devices in order to prevent needlestick injuries
      and provide safe, effective and individualised care for their patients.

PMID- 22875162
TI  - Considerations for managing stoma complications in the community.
AB  - Complications related to stoma surgery can occur immediately post surgery or
      following discharge from hospital, and will either resolve spontaneously or
      become a difficult management problem for both the stoma patient and healthcare
      practitioner. In the early stages of rehabilitation, the patient with a stoma
      relies heavily on the expertise of the healthcare practitioner to assist them in
      returning to the lifestyle they once enjoyed. Literature acknowledges that
      adjustment to life with a stoma depends largely on whether complications
      following the creation of a stoma are persistent (Bekkers et al, 1996; Taylor,
      1999; Cottam and Richards, 2006). Evidence demonstrates that prolonged unresolved
      stoma problems hinder adaptation and adjustment to the stoma (Bekkers et al,
      1996; Williams et al, 2010), therefore, it is important for the healthcare
      practitioner to be well informed and  skilled regarding common stoma problems.
      This article aims to highlight common stoma complications and offer guidance on
      evidence-based management of such problems to inform healthcare practitioners
      working in the community setting.

PMID- 22875163
TI  - Maximising psychiatric nurses'  contribution to interdisciplinary working.
AB  - Internationally, the deinstitutionalization of psychiatric care has resulted in
      expanded roles for mental health nurses within a community interdisciplinary team
      setting. This presents an opportunity for mental health nurses to improve service
      delivery. This opportunity also results in a more empowered nursing team. This
      article identifies change issues within one community psychiatric nursing team
      and the team's contribution to an improved service delivery where service users
      can avail of same day assessment for crisis referrals, a reduction in waiting
      times for assessment and co-ordinated delivery of care with an identified key
      worker utilizing a recovery model philosophy.

PMID- 22875164
TI  - ENRICH: a new innovation to facilitate dementia research in care homes.

PMID- 22875165
TI  - Chemotherapy in the community:  the importance of patient assessment.
AB  - The use of chemotherapy has expanded considerably in the UK in recent years, with
      an increase of around 60% in the amount of chemotherapy delivered over a four
      year period (National Chemotherapy Advisory Group (NCAG), 2009). This has led to
      an increased demand for the delivery of chemotherapy, putting pressure on
      existing cancer services. Combined with the current political agenda which aims
      to improve the convenience and experience of health for patients' this has
      prompted the reorganisation of chemotherapy services, with a movement away from
      the delivery of chemotherapy in dedicated cancer centres to community-based
      models of care. This article discusses the implications of these changes for
      community nurses with regard to their role in the assessment of patients
      receiving chemotherapy.

PMID- 22875166
TI  - Making a difference through QELCA:  a time to engage community nurses.

PMID- 22875167
TI  - Measuring and demonstrating district nursing's clinical effectiveness.

PMID- 22875168
TI  - Further legal protection needed for nurses who report poor practice?
AB  - There are persistent calls from Government, health regulators and even the
      Parliamentary health select committee for health professionals to report poor
      practice. The Government argues that district nurses who blow the whistle on
      substandard care will be protected by changes to the NHS Constitution for
      England. However, a recent decision of the Court of Appeal shows that
      whistleblowers who are subject to bullying and recriminations from colleagues are
      not protected by the law and cannot claim compensation. In this article Richard
      Griffith and Cassam Tengnah review the law protecting whistleblowers, and
      discusses ways in which district nurses who have concerns can safely report poor
      practice.

PMID- 22875169
TI  - Weight in old age.

PMID- 22875170
TI  - Differences in histopathological evaluation of standard lymph node dissections
      result in differences in nodal count but not in survival.
AB  - OBJECTIVE: To analyse whether the reported differences in nodal yield at pelvic
      lymph node dissection (PLND) for bladder cancer, between two hospitals, are
      reflected in the survival rates. PATIENTS AND METHODS: We assessed follow-up data
      of all 174 patients (mean age: 62.7, median follow-up: 3 years) who underwent
      PLND between 1 January 2007 and 31 December 2009 at two different hospitals. PLND
      was performed according to a standardized template by the same urologists for
      comparable bladder cancer patients. Mean number of reported lymph nodes was 16 at
      hospital A versus 28 at hospital B. We compared the overall survival (OS),
      disease-specific survival (DSS) and recurrence-free survival (RFS) between both
      cohorts and performed a multivariate analysis. RESULTS: The cumulative
      probability for 2-year OS, DSS and RFS for hospital A are 61, 64 and 54 %, versus
      58, 58 and 53 % for hospital B, respectively. Kaplan-Meier survival curves did
      not reveal statistically significant differences between both groups (OS: p log
      rank = 0.75, DSS: p log-rank = 0.56, and RFS: p log-rank = 0.80). Also after
      adjustment for pT stage and neoadjuvant chemotherapy, survival was not
      significantly different between hospital A and hospital B. CONCLUSION: Despite
      differences in lymph node yield in PLND specimens, this study reveals no
      significant differences in survival outcomes between both hospitals. Standardized
      histopathological methods should be agreed upon by pathologists before
      integrating nodal yield and subsequent lymph node density as indicators of the
      quality of surgery and as prognostic factors.

PMID- 22875171
TI  - Myocardial fibrosis and quality of life in patients with non-ischemic
      cardiomyopathy: a cardiovascular magnetic resonance imaging study.
AB  - Myocardial fibrosis (MF) is a common pathophysiologic endpoint in non-ischemic
      cardiomyopathy and may be identified by late gadolinium enhancement (LGE) MRI.
      While associated with future cardiovascular events in hypertrophic cardiomyopathy
      (HCM) and dilated cardiomyopathy (DCM) the influence of MF on interim quality of
      life (QOL) has not been explored. In this study we investigate for associations
      between MF and validated indices of QOL in patients with HCM and DCM. Ninety
      eight patients with known cardiomyopathy (n = 56-HCM/n = 42-DCM) underwent LGE
      MRI in addition to standardized testing for QOL using the disease-specific
      Minnesota Living With Heart Failure (MLWHF) and the generic SF-12 questionnaires.
      LGE-MRI images were blindly analyzed for the presence and volume of MF using
      validated techniques. All analyses were stratified according to cardiomyopathy
      sub-type. The mean age of the population was 56.8 +/- 12.9 years. MF was
      identified in 82 % of patients with HCM and 74 % of patients with DCM with
      respective mean MF burdens of 20.0 and 13.7 % of the left ventricular mass (p =
      0.008). QOL scores for those with HCM or DCM, as assessed by both MLWHF and SF
      12, were not significantly different between those with versus those without MF,
      and showed no association with MF burden by quantitative signal analysis. In this
      study we identified no association between QOL and MF burden by LGE-MRI in
      patients with HCM or DCM. Therefore, the severity of underlying myocardial tissue
      disease, a recognized substrate for ventricular arrhythmia, cannot and should not
      be inferred from the patient's symptom status or QOL.

PMID- 22875172
TI  - Assessment of a transcatheter heart valve prosthesis with multidetector computed
      tomography: in vitro and in vivo imaging characteristics.
AB  - Multidetector-row computed tomography (MDCT) image quality (IQ) of the commonly
      implanted Sapien prosthesis was assessed both in vitro and in vivo. The
      prosthesis was imaged in an in vitro model with a 256-slice CT system under
      pulsatile conditions using three protocols (1) retrospectively ECG-gating at 120
      kV/600 mAs and (2) 140 kV/406 mAs, and (3) prospective triggering at 120 kV/210
      mAs (10 acquisitions per protocol). After reconstruction in three perpendicular
      planes, IQ of the supra-,peri-,sub-,and intraprosthetic as well as leaflet
      regions was scored on a four-point scale (1 = non-diagnostic, 2 = moderate, 3 =
      good and 4 = excellent) by two observers. IQ was also assessed for twenty-one
      post-operative scans. The in vitro scans of the two retrospective protocols and
      twenty-one in vivo scans were analyzed during systole and diastole. The
      prospectively triggered scans were analyzed during diastole. Except for the valve
      leaflets in 5 systolic reconstructions, the in vitro scores were moderate to
      excellent. In vivo, 7 systolic and 3 diastolic reconstructions of the valve
      leaflets were non-diagnostic as well as 3 peri-prosthetic regions in diastole.
      All other scores were moderate to excellent. The Sapien prosthesis surrounded by
      a radiopaque stainless steel stent can be visualized with MDCT with moderate to
      good IQ, except for the valve leaflet region that has generally non-diagnostic or
      moderate IQ.

PMID- 22875174
TI  - Highly enantioselective Friedel-Crafts alkylation of indoles and pyrrole with
      beta,gamma-unsaturated alpha-ketoesters catalyzed by heteroarylidene-tethered
      bis(oxazoline) copper complexes.
AB  - The simple and cheap chiral catalyst, heteroarylidene-tethered Ph-bis(oxazoline)
      Cu(OTf)(2), can efficiently catalyze the asymmetric F-C alkylation of indoles and
      pyrrole with beta,gamma-unsaturated alpha-ketoesters. The 3-indolyl adducts were
      obtained in up to >99% ee. Moreover, the 2-pyrrolyl adducts were achieved in up
      to 92% ee for the first time.

PMID- 22875173
TI  - The influence of employment social support for risk and prognosis in nonspecific
      back pain: a systematic review and critical synthesis.
AB  - PURPOSE: To examine the influence of employment social support type (e.g. co
      worker, supervisor, general support) on risk of occurrence of low back pain, and
      prognosis (e.g. recovery, return to work status) for those who have low back
      pain. METHODS: Systematic search of seven databases (MEDLINE, Embase, PsychINFO,
      CINAHL, IBSS, AMED and BNI) for prospective or case-control studies reporting
      findings on employment social support in populations with nonspecific back pain.
      Data extraction and quality assessment were carried out on included studies. A
      systematic critical synthesis was carried out on extracted data. RESULTS: Thirty
      two articles were included that describe 46 findings on the effect of employment
      social support on risk of and prognosis of back pain. Findings show that there is
      no effect of co-worker, supervisor or general work support on risk of new onset
      back pain. Weak effects of employment support were found for recovery and return
      to work outcomes; greater levels of co-worker support and general work support
      were found to be associated with less time to recovery or return to work.
      CONCLUSIONS: The evidence suggests that the association between employment
      support and prognosis may be subject to influence from wider concepts related to
      the employment context. This review discusses these wider issues and offers
      directions for future research.

PMID- 22875175
TI  - 5,5'-Azoxytetrazolates--a new nitrogen-rich dianion and its comparison to 5,5'
      azotetrazolate.
AB  - A modification of the synthesis of sodium 5,5'-azotetrazolate pentahydrate,
      described by Thiele in 1898, yields the unknown and unexpected corresponding 5N
      oxido derivative sodium 5,5'-azoxybistetrazolate pentahydrate (Na(2)zTO.5H(2)O,
      1). Purification was achieved by recrystallization based on the better solubility
      of Na(2)zTO.5H(2)O in water. Different nitrogen-rich salts, such as the
      diammonium (3), the dihydroxylammonium (4), the bis-diaminoguanidinium (5), the
      bis-triaminoguanidinium (6) and the diaminouronium salt (7), have been prepared
      using metathesis reactions starting from barium 5,5'-azoxybistetrazolate
      pentahydrate (2) and ammonium, hydroxylammonium, diaminoguanidinium or
      diaminouronium sulfate and triaminoguanidinium chloride, respectively. The
      nitrogen rich azoxy-derivatives 3-7 were characterized using NMR, IR and Raman
      spectroscopy, mass spectrometry and elemental analysis. Additionally the solid
      state structures of 3, 4, 5 and 7 were determined by single crystal X-ray
      diffraction. The heats of formation of 3 and 4 and their corresponding azo
      tetrazolate derivatives were calculated by the atomization method based on CBS-4M
      enthalpies. With these values and the crystal densities, several detonation
      parameters such as the detonation velocity, detonation pressure and specific
      impulse were calculated (EXPLO5) and compared. The sensitivities towards shock
      (BAM drophammer), friction (BAM friction tester) and electrostatic discharge of
      the described compounds were determined.

PMID- 22875176
TI  - Comparative mapping in watermelon [Citrullus lanatus (Thunb.) Matsum. et Nakai].
AB  - The first single-nucleotide polymorphism (SNP) maps for watermelon [Citrullus
      lanatus (Thunb.) Matsum. et Nakai] were constructed and compared. Three
      populations were developed from crosses between two elite cultivars, Klondike
      Black Seeded * New Hampshire Midget (KBS * NHM), an elite cultivar and wild egusi
      accession, Strain II * PI 560023 (SII * Egusi) and an elite cultivar and a wild
      citron accession, ZWRM50 * PI 244019 (ZWRM * Citroides). The SII * Egusi and ZWRM
      * Citroides F(2) populations consisted of 187 and 182 individuals respectively
      while the KBS * NHM recombinant inbred line (RIL) population consisted of 164
      lines. The length of the genetic maps were 1,438, 1,514 and 1,144 cM with average
      marker distances of 3.8, 4.2, and 3.4 cM for the KBS * NHM, SII * Egusi and ZWRM
      * Citroides populations, respectively. Shared markers were used to align the
      three maps so that the linkage groups (LGs) represented the 11 chromosomes of the
      species. Marker segregation distortion were observed in all three populations,
      but was highest (12.7 %) in the ZWRM * Citroides population, where Citroides
      alleles were favored. The three maps were used to construct a consensus map
      containing 378 SNP markers with an average distance of 5.1 cM between markers.
      Phenotypic data was collected for fruit weight (FWT), fruit length (FL), fruit
      width (FWD), fruit shape index (FSI), rind thickness (RTH) and Brix (BRX) and
      analyzed for quantitative trait loci (QTL) associated with these traits. A total
      of 40 QTL were identified in the three populations, including major QTL for fruit
      size and shape that were stable across genetic backgrounds and environments. The
      present study reports the first SNP maps for Citrullus and the first map
      constructed using two elite parents. We also report the first stable QTL
      associated with fruit size and shape in Citrullus lanatus. These maps, QTL and
      SNPs should be useful for the watermelon community and represent a significant
      step towards the potential use of molecular tools in watermelon breeding.

PMID- 22875177
TI  - A single nucleotide polymorphism at the Vrn-D1 promoter region in common wheat is
      associated with vernalization response.
AB  - Facultative wheat varieties adapt to a particular environment. But the molecular
      basis for the facultative growth habit is not clear relative to winter and spring
      growth habit. Two sets of wheat varieties were chosen for this study. Set 1
      comprised ten spring accessions and Set 2 comprised ten facultative accessions.
      All accessions had been tested by the previously described allele-specific
      markers and shown having the same allelic composition of vrn-A1 vrn-B1 Vrn-D1 and
      vrn-B3. Here we examined whether differences in growth habit might be associated
      with as yet unidentified sequence variation at Vrn-D1 locus. A region including
      the intron 1 deletion, the entire reading frame from a cDNA template and a part
      of promoter region of the dominant Vrn-D1 gene in each of the accessions was
      sequenced, and a single nucleotide polymorphism was found between facultative
      accessions and spring accessions in the CArG-box at the promoter region. The
      novel allele in facultative accessions was designated as Vrn-D1b. The
      investigation of an F(2) population segregating for Vrn-D1b and Vrn-D1a
      (previously, Vrn-D1) in the greenhouse under long days without vernalization
      showed that the plants with Vrn-D1b homozygous allele headed 32 days later and
      had about three more leaves than the plants with Vrn-D1a homozygous allele. As
      Vrn-D1b has the same deletion in intron 1 as Vrn-D1a, and, in addition, a single
      nucleotide mutation at promoter region, and is associated with facultative growth
      habit, we suggest that the promoter mutation may modify the basal activity level
      of an allele of VRN1 that is already active (due to the loss of segments in
      intron 1). Our finding further supports that both the promoter and intron 1
      regulatory affect vernalization response and work independently.

PMID- 22875179
TI  - An NHS fit for purpose?
AB  - When I first started looking after older people, the average patient was 30 or 40
      years older than I was. Almost 30 years later, the average patient is still 30-40
      years older than I am. Have I discovered the fountain of eternal youth? No, but
      perhaps I should ask my patients where it is.

PMID- 22875178
TI  - Optofluidic device for label-free cell classification from whole blood.
AB  - We demonstrated a unique optofluidic lab-on-a-chip device that can measure
      optically encoded forward scattering signals. From the design of the spatial
      pattern, we can measure the position and velocity of each cell in the flow and
      generate a 2-D cell distribution plot over the cross section of the channel.
      Moreover, we have demonstrated that the cell distribution is highly sensitive to
      its size and stiffness. The latter is an important biomarker for cell
      classification and our method offers a simple and unequivocal method to classify
      cells by their size and stiffness. We have proved the concept using live and
      fixed HeLa cells. Due to the stiffness and size difference of neutrophils
      compared to other types of white blood cells, we have demonstrated detection of
      neutrophils from other blood cells. Finally, we have performed the test using 5
      MUL of human blood. In a greatly simplified blood preparation process, skipping
      the usual steps of anticoagulation, centrifuge, antibody labelling or staining,
      filtering, etc., we have demonstrated that our device and detection principle can
      count neutrophils in whole human blood. Our system is compact, inexpensive and
      simple to fabricate and operate, having a commodity laser diode and a Si PIN
      photoreceiver as the main pieces of hardware. Although the results are still
      preliminary, the studies indicate that this optofluidic device holds promise to
      be a point-of-care and home care device to measure neutrophil concentration,
      which is the key indicator of the immune functions for cancer patients undergoing
      chemotherapy.

PMID- 22875180
TI  - Recognising and managing  allergic disease in the community.
AB  - Allergic disease and its symptoms, whether seasonal or perennial, can have a
      significant impact on individuals' quality of life. Asthma, allergic rhinitis,
      eczema, urticaria and food allergy are among the common allergies that nurses may
      encounter in the community. This article discusses the causes of allergic
      disease, the importance of considering allergen avoidance, and the alternative
      treatment options available.

PMID- 22875181
TI  - Breaking the silence:  helping men with erectile dysfunction.
AB  - Erectile dysfunction is a condition that is often under-reported. This article
      provides the community nurse with a brief overview of erectile dysfunction in the
      context of sexual health and its importance to wellbeing. The article outlines
      issues concerning epidemiology, the possible causes of erectile dysfunction and
      the impact the condition can have on the man's quality of life. Often men with
      erectile dysfunction report being stigmatised, feeling shame and experiencing
      guilt. The role of the community nurse in assessing, making a diagnosis and
      helping the man with the condition is described. The article emphasises the fact
      that in order to offer care effectively and competently the community nurse must
      be up to date and knowledgeable concerning the condition.

PMID- 22875182
TI  - Resting Doppler ankle brachial pressure index measurement: a literature review.
AB  - Peripheral vascular disease (PVD) is under-diagnosed in primary and acute
      settings. The use of Doppler ankle brachial pressure index (ABPI) is effective in
      diagnosing PVD , aid in determining aetiology of leg ulcers and is cost efficient
      in reducing the effects of atherosclerosis and cardiovascular events. The aim of
      this literature review was to review practitioners' experience in using Doppler
      ABPI, different skills used to measure ABPI and to examine practitioners'
      confidence in ABPI. The findings identified variation in method for Doppler
      measurement: including position of the artery, arm measurement, resting period
      and type of equipment for measuring blood pressure, variations in practitioners'
      training and experience have demonstrated variability in ABPI results. Although
      limited in number, the studies have demonstrated knowledge gap, and the need for
      training among health professionals.

PMID- 22875184
TI  - A necessary change: the transfer of care from hospital to community.
AB  - While there is ample evidence for the benefits of diverting resources from
      hospital delivery out to the community in terms of improved patient safety, very
      little is known about the impact on a healthcare provider's efficiency and output
      (Ovretveit, 2009).

PMID- 22875185
TI  - Mentoring community-based trainee assistant practitioners: a case study.
AB  - The healthcare workforce is changing, and the introduction of assistant
      practitioner roles in the community presents exciting opportunities for the
      unregistered workforce. Healthcare assistants wishing to become assistant
      practitioners are undertaking foundation degrees. During this period of study,
      they require support and supervision from a mentor to perform competencies;
      however, mentors are often poorly prepared for this role. This small-scale
      qualitative exploratory study sought to gain trainee assistant practitioner
      (TAP), mentor and management perspective on the level of support needed. Findings
      indicate that TAPs struggle for recognition and student/learner status; there was
      an assumption that mentors would be adequately equipped to mentor TAPs, and poor
      mentor preparation was linked to negative student experiences. This article
      considers the key factors, time and commitment, required to support TAP learners
      in the workplace. Further, it questions who is best placed to mentor TAPs.
      Recommendations include an increased level of preparation for mentors, a joint
      induction programme for TAPs and mentors, a raised profile of the  assistant
      practitioner role within the wider healthcare team, recognition of the TAP as a
      learner, and allocated time for quality mentorship.

PMID- 22875186
TI  - Inside the mind of a relative  at the end of life.
AB  - Health professionals often encounter relatives who have different wishes to those
      of the dying patient. There are relatives who perceive themselves as the
      appointed mouthpiece for the dying patient, answering questions intended for the
      patient, while others request that professionals do not break any bad news to the
      patient. However, if we are going to follow closely the ideology of palliative
      care, where we care for both the patient and their relatives' needs, it is
      important that we try to understand the reasons relatives may act in this way.

PMID- 22875187
TI  - Changes and sticking points in adult safeguarding: a discussion.
AB  - The care and treatment of vulnerable adults was the subject of regular public and
      media concern in 2011. This article discusses the potential impact of these
      concerns on community nursing practice and reflects on the ways in which such
      concerns may be discussed in professional development activities. It alerts
      nurses to the importance of considering the effects on patients and carers of
      exposure to negative findings from inquiries and inspections. It identifies ways
      in which professional development opportunities can be used to update general
      skills in safeguarding practice. These are likely to be of growing importance to
      the work of community nurses in the context of an ageing society and occasional
      potential conflicts between patients and carers. Keeping abreast of legal
      frameworks will be required of nurses if they are to advise and to advocate for
      their patients.

PMID- 22875188
TI  - Self-management: preparing for the impact of the 'Nicholson challenge'.
AB  - In May, 19 members of the newly formed Expert Patients Programme Community
      Interest Company (EPP CIC) Advisory Panel met to discuss, 'What impact is the
      'Nicholson challenge' having on self-management and patient-centred care?' The
      panel was made up of experts in self-management and care pathway design or
      implementation, key opinion formers in the health community, and other partners
      who enable access to self-management.

PMID- 22875189
TI  - Changes to criminal records checks used to safeguard vulnerable patients.
AB  - The Protection of Freedoms Act 2012 is introducing changes to the Criminal
      Records Bureau (CRB) checks carried out on those people who work with vulnerable
      groups. The new law is the coalition Government's response to the criticism of
      the Safeguarding Vulnerable Group Act 2006. It will merge the CRB and Independent
      Safeguarding Authority into a new Disclosure and Barring Service and will enhance
      the rights of applicants to challenge the CRB's right to disclose non-conviction
      information as part of an enhanced criminal records check. In the first of two
      articles on the Protection of Freedoms Act 2012, Richard Griffith and Cassam
      Tengnah discuss the current framework for disclosing criminal records and the
      impact of the changes on district nurses applying for new posts.

PMID- 22875190
TI  - QNI celebrates 125 years.
AB  - The Queen's Nursing Institute was founded in 1887 with the grant of L70000 by
      Queen Victoria from the Women's Jubilee Fund. Originally called the 'Queen
      Victoria's Jubilee Institute for Nurses', it was set up with the objective of
      providing the 'training, support, maintenance and supply' of nurses for the sick
      poor.

PMID- 22875192
TI  - An interrupted PET coupled TBET process for the design of a specific receptor for
      Hg2+ and its intracellular detection in MCF7 cells.
AB  - A new coumarin-rhodamine conjugate constitutes a unique example of the
      interrupted PET coupled TBET response for developing an imaging reagent for
      determining the intracellular distribution of Hg(2+) in MCF7 cells exposed to
      [Hg(2+)] as low as 2 ppb.

PMID- 22875191
TI  - Relatively high serum vitamin D levels do not impair the antibody response to
      encapsulated bacteria.
AB  - Vitamin D skews the immune system towards a more tolerogenic state. Therefore, a
      relatively high vitamin D status, i.e., within the normal physiological range,
      might result in a lower antibody response to infection and vaccination. We
      hypothesized, however, that vitamin D is primarily important in establishing
      immune homeostasis, implying that a relatively high vitamin D status would not
      hamper an adequate antibody response against pathogens. Our results show that the
      vitamin D status did not differ between responders and hypo-responders in
      patients infected with Streptococcus pneumoniae, as well as patients vaccinated
      against S. pneumoniae, Neisseria meningitidis type C (MenC), and/or Haemophilus
      influenzae type b (Hib). Furthermore, specific IgG titers were not associated
      with the vitamin D status in patients vaccinated against S. pneumoniae and MenC,
      while there was a weak inverse association in Hib-vaccinated patients. These data
      indicate that a relatively high vitamin D status does not seem to hamper an
      adequate antibody response upon infection or vaccination, suggesting that vitamin
      D, in this setting, is not immunosuppressive.

PMID- 22875193
TI  - Unusual nitro-coordination of europium(III) and terbium(III) with pyridinyl
      ligands.
AB  - A new ligand family based on picoline, bipyridine and terpyridine containing a
      nitro moiety has been synthesized and its coordination and sensitization ability
      for lanthanide ions has been studied. Three new complexes were characterized by X
      ray single crystal diffraction and all three show uncommon coordination of the
      nitro moiety to the lanthanide ion. 5cTb, a terpyridine-nitro derivative with
      Tb(NO(3))(3), crystallizes in the orthorhombic space group Pbca with a =
      15.125(3), b = 13.776(3), c = 18.716(4) A, and V = 3899.8(13) A(3) and is
      isostructural with its Eu(III) analog (5cEu) with cell parameters a = 15.1341(4),
      b = 13.7070(4), c = 18.8277(5) A. 6Eu, a tripodal amine with a nitro-derivatized
      pyridine with Eu(CF(3)SO(3))(3), crystallizes in the triclinic space group P1
      with a = 11.067(2), b = 11.633(2), c = 12.772(3) A, alpha = 110.94(3), beta =
      97.49(3), gamma = 91.42(3) degrees  and V = 1518.1(5) A(3). Finally, ligand 5a, a
      bipyridine-nitro derivative, crystallizes in the orthorhombic space group P2(1)/n
      with a = 3.7128(3), b = 11.7806(8), c = 19.9856(14) A, beta = 92.925(2) degrees 
      and V = 873.01(11) A(3). All four ligands show sensitization of Eu(III) and
      Tb(III) luminescence.

PMID- 22875194
TI  - Impact reduction during running: efficiency of simple acute interventions in
      recreational runners.
AB  - Running-related stress fractures have been associated with the overall impact
      intensity, which has recently been described through the loading rate (LR). Our
      purpose was to evaluate the effects of four acute interventions with specific
      focus on LR: wearing racing shoes (RACE), increasing step frequency by 10 %
      (FREQ), adopting a midfoot strike pattern (MIDFOOT) and combining these three
      interventions (COMBI). Nine rearfoot-strike subjects performed five 5-min trials
      during which running kinetics, kinematics and spring-mass behavior were measured
      for ten consecutive steps on an instrumented treadmill. Electromyographic
      activity of gastrocnemius lateralis, tibialis anterior, biceps femoris and vastus
      lateralis muscles was quantified over different phases of the stride cycle. LR
      was significantly and similarly reduced in MIDFOOT (37.4 +/- 7.20 BW s(-1), -56.9
      +/- 50.0 %) and COMBI (36.8 +/- 7.15 BW s(-1), -55.6 +/- 29.2 %) conditions
      compared to NORM (56.3 +/- 11.5 BW s(-1), both P < 0.001). RACE (51.1 +/- 9.81 BW
      s(-1)) and FREQ (52.7 +/- 11.0 BW s(-1)) conditions had no significant effects on
      LR. Running with a midfoot strike pattern resulted in a significant increase in
      gastrocnemius lateralis pre-activation (208 +/- 97.4 %, P < 0.05) and in a
      significant decrease in tibialis anterior EMG activity (56.2 +/- 15.5 %, P <
      0.05) averaged over the entire stride cycle. The acute attenuation of foot-ground
      impact seems to be mostly related to the use of a midfoot strike pattern and to a
      higher pre-activation of the gastrocnemius lateralis. Further studies are needed
      to test these results in prolonged running exercises and in the long term.

PMID- 22875195
TI  - Cancer outcomes and all-cause mortality in adults allocated to metformin:
      systematic review and collaborative meta-analysis of randomised clinical trials.
AB  - AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer
      risk by approximately one-third. We examined cancer outcomes and all-cause
      mortality in published randomised controlled trials (RCTs). METHODS: RCTs
      comparing metformin with active glucose-lowering therapy or placebo/usual care,
      with minimum 500 participants and 1-year follow-up, were identified by systematic
      review. Data on cancer incidence and all-cause mortality were obtained from
      publications or by contacting investigators. For two trials, cancer incidence
      data were not available; cancer mortality was used as a surrogate. Summary RRs,
      95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects
      meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described
      14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers
      during 51,681 person-years. RRs for all-cause mortality were available from 13
      RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes
      in people randomised to metformin compared with any comparator were 1.02 (95% CI
      0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of
      active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of
      placebo/usual care comparator trials. The summary RR for all-cause mortality was
      0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta
      analysis of currently available RCT data does not support the hypothesis that
      metformin lowers cancer risk by one-third. Eligible trials also showed no
      significant effect of metformin on all-cause mortality. However, limitations
      include heterogeneous comparator types, absent cancer data from two trials, and
      short follow-up, especially for mortality.

PMID- 22875197
TI  - Considerations in determination of residual moisture in lyophilized demineralized
      bone matrix: the role of residual moisture analyzers.
AB  - The objective of this study is to determine whether a residual moisture analyzer
      (RMA) can be an acceptable instrument for measuring the residual moisture in
      lyophilized demineralized bone matrix (DBM). Instruments from two different
      manufacturers with differing configurations and controls were compared: the Ohaus
      MB45 and Arizona Instrument MAX4000XL. The effects of various factors such as
      test temperature, drying profile, end point criteria, lift compensation, chamber
      configuration, and rehydration on residual moisture (RM) are examined. The
      performance of the RMAs is based on their ability to reproduce RM results
      obtained by the current standard gravimetric method. RMAs provide reliable,
      accurate and reproducible results in a number of industries that rely on the
      determination of RM. We hypothesize that RMAs are suitable for measuring RM in
      DBM and provide validation study data with optimized settings for these two
      instruments. Potentially, such studies will provide justification for allowance
      of this methodology as an acceptable alternative to the current gravimetric
      method allowed by American Association of Tissue Banks Standards.

PMID- 22875198
TI  - Development of a decellularised dermis.
AB  - The purpose of this investigation was to develop a decellularised human dermis
      suitable for allografting. Samples of human skin were obtained from deceased
      donors and taken through a series of steps to remove all cellular material. The
      steps were: chemical removal of the epidermis, disinfection, lysing of cells in
      hypotonic buffer, a detergent treatment and a nuclease buffer to remove residual
      nuclear material. Histological preparations of the decellularised dermis produced
      were then investigated. In addition residual DNA content, structural strength,
      collagen denaturation, cytotoxicity and in vivo tissue reactivity following
      implantation in a murine model were examined. For all donors tested there was no
      change in morphology as viewed by light microscopy. Mean DNA removal was
      evaluated at 92.1%. There were no significant changes in structural strength or
      evidence of collagen degradation. The tissue did not appear to be cytotoxic or
      elicit an immune response when implanted in the mouse model. A decellularised
      tissue has been developed that would appear to be suitable for a range of
      surgical procedures.

PMID- 22875196
TI  - Does the gut microbiota have a role in type 1 diabetes? Early evidence from
      humans and animal models of the disease.
AB  - Despite years of appreciating the potential role of environment to influence the
      pathogenesis of type 1 diabetes, specific agents or mechanisms serving in such a
      capacity remain ill defined. This is exceedingly disappointing as the
      identification of factors capable of modulating the disease, either as triggers
      or regulators of the autoimmune response underlying type 1 diabetes, would not
      only provide clues as to why the disorder develops but, in addition, afford
      opportunities for improved biomarkers of disease activity and the potential to
      design novel therapeutics capable of disease abatement. Recent improvements in
      sequencing technologies, combined with increasing appreciation of the role of
      innate and mucosal immunity in human disease, have stirred strong interest in
      what is commonly referred to as the 'gut microbiota'. The gut (or intestinal)
      microbiota is an exceedingly complex microenvironment that is intimately linked
      with the immune system, including the regulation of immune responses. After
      evaluating evidence supporting a role for environment in type 1 diabetes, this
      review will convey current notions for contributions of the gut microbiota to
      human health and disease, including information gleaned from studies of humans
      and animal models for this autoimmune disorder.

PMID- 22875199
TI  - Jorge Morales Pedraza: The use of the ionization technique for tissue
      sterilisation: the International Atomic Energy Agency (IAEA) experience.

PMID- 22875200
TI  - Sporicidal efficacy of genipin: a potential theoretical alternative for
      biomaterial and tissue graft sterilization.
AB  - Terminal sterilization of musculoskeletal allografts by gamma radiation minimizes
      the risk of disease transmission but impairs allograft mechanical properties.
      Commonly employed crosslinking agents can sterilize tissues without affecting
      mechanical properties adversely; however, these agents are toxic. Genipin is
      reported to be a benign crosslinking agent that strengthens mechanical properties
      of tissues; however, the antimicrobial capacity of genipin is largely unknown.
      The present study's aims were: (1) to assess the sporicidal potential of genipin,
      (2) to improve antimicrobial capacity by changing chemical and physical treatment
      conditions. To establish genipin's sterilization potential Bacillus subtilis var.
      niger spore strips were treated with 0-10% genipin in PBS or in 1:1 DMSO:PBS up
      to 72 h at room temperature (RT). Sterilizing doses and concentrations of genipin
      were used to treat B. pumilus and Geobacillus stearothermophilus spores to assess
      broader spectrum sporicidal activity of genipin. Scanning electron microscopy
      (SEM) was performed to evaluate gross morphological changes after genipin
      treatment. Optimal sterilization conditions were determined by evaluating the
      effects of temperature (RT-50  degrees C), DMSO:PBS ratio (0:100-100:0), and
      treatment duration (24-72 h) on B. subtilis. Genipin penetration of full
      thickness bovine patellar tendon and cortical bone specimens was observed to
      assess the feasibility of the agent for treating grafts. Initial studies showed
      that after 72 h of treatment at RT with 0.63-10% genipin/DMSO:PBS B. subtilis
      spore strips were sterilized; 0.63% genipin/PBS did not sterilize spore strips at
      72 h at RT. Genipin doses and concentrations that sterilized B. subtilis spore
      strips sterilized B. pumilus and G. stearothermophilus spore strips. SEM revealed
      no gross morphological differences between untreated and treated spores.
      Treatment optimization resulted in sterilization within 24 h with 100% PBS, and
      DMSO facilitated sporicidal activity. Genipin penetrated full thickness patellar
      tendon specimens and 3.72 +/- 0.58 mm in cortical bone specimens. Genipin
      sterilizes B. subtilis, B. pumilus, and G. stearothermophilus spore strips. It
      penetrates soft and hard tissues at doses previously shown to be non-toxic and to
      improve mechanical strength in collagen-rich soft tissues. Further studies are
      indicated to assess genipin's effects on the mechanical properties of genipin
      sterilized grafts, the ability of genipin to eradicate infectious species other
      than spores, and to assess whether sterilant activity persists after penetrating
      tissues and biomaterials.

PMID- 22875201
TI  - Transformations in oxides induced by high-energy ball-milling.
AB  - This paper, by no means exhaustive, focuses on high-energy ball-milling of
      oxides, on their mechanically induced changes and on the consequences of such
      changes on their physical and chemical properties. High-energy ball-milling
      offers a fortunate combination of technical simplicity and of complexity both of
      physical mechanisms which act during milling and of mechanosynthesized materials.
      Its basic interest, which stems from the large diversity of routes it offers to
      prepare oxides either directly or indirectly, is illustrated with various
      families of oxides. The direct path is to be favoured when as-milled oxides are
      of interest per se because of their nanocrystalline characteristics, their
      defects or their modified structures which result from mechanically driven phase
      transformations. The indirect path consists of a sequence of steps starting with
      mechanically activated oxides which may be subsequently just annealed or
      submitted to a combination of thermal treatments, with the possible occurrence of
      various chemical reactions, to prepare the sought-after materials with potential
      gains in processing temperatures and times. High energy ball-milling of oxides is
      more and more currently used to activate powders and to prepare nano-oxides at
      moderate temperatures. The interest of an activation step is well illustrated by
      the broad development of doped titania powders, synthesized by heat treatment of
      pre-ground reactants, for photocatalytic applications or to develop antibacterial
      materials. Another important class of applications of high-energy ball-milling is
      the formation of composites. It is exemplified here with the case of oxide
      dispersed strengthened alloys whose properties are considerably improved by a
      dispersion of ultra-stable nanosized oxides whose formation mechanisms were
      recently described. The basic understanding of the mechanisms by which oxides or
      oxide mixtures evolve by high-energy ball-milling appears to be less advanced
      than it is for metallic materials essentially because of the overall complexity
      of the oxide structures, of their surfaces, of their defects and of their
      mechanical behavior.

PMID- 22875202
TI  - Continuous flow multi-stage microfluidic reactors via hydrodynamic microparticle
      railing.
AB  - "Multi-stage" fluidic reactions are integral to diverse biochemical assays;
      however, such processes typically require laborious and time-intensive fluidic
      mixing procedures in which distinct reagents and/or washes must be loaded
      sequentially and separately (i.e., one-at-a-time). Microfluidic processors that
      enable multi-stage fluidic reactions with suspended microparticles (e.g.,
      microbeads and cells) to be performed autonomously could greatly extend the
      efficacy of lab-on-a-chip technologies. Here we present a single-layer
      microfluidic reactor that utilizes a microfluidic railing methodology to
      passively transport suspended microbeads and cells into distinct, adjacent
      laminar flow streams for rapid fluidic mixing and assaying. Four distinct
      molecular synthesis processes (i.e., consisting of 48 discrete fluidic mixing
      stages in total) were accomplished on polystyrene microbead substrates (15 MUm in
      diameter) in parallel, without the need for external observation or regulation
      during device operation. Experimental results also revealed successful railing of
      suspended bovine aortic endothelial cells (approximately 13 to 17 MUm in
      diameter). The presented railing system provides an effective continuous flow
      methodology to achieve bead-based and cell-based microfluidic reactors for
      applications including point-of-care (POC) molecular diagnostics, pharmacological
      screening, and quantitative cell biology.

PMID- 22875203
TI  - A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a
      more precise definition of scalp health.
AB  - Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the
      pathophysiological understanding is still incomplete but suggests a role of
      Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal
      responses. The objective of this report is to review published literature from in
      vivo studies of D/SD populations to provide a more complete description of
      overall scalp health. New biomolecular capabilities establish a depth of
      pathophysiological understanding not previously achievable with traditional means
      of investigation. Biomarkers representing inflammation, hyper-proliferation and
      barrier function are all perturbed by the D/SD condition and robustly respond to
      therapeutic resolution. These biomarkers can be sampled noninvasively, enabling
      their use in routine clinical evaluations as either surrogate endpoints or
      complementary ones to classical signs/symptoms to broaden the etiological
      learning.

PMID- 22875204
TI  - External manual reduction of paediatric idiopathic ileocolic intussusception with
      US assistance: a new, standardised, effective and safe manoeuvre.
AB  - BACKGROUND: The ultimate goal in the management of paediatric ileocolic
      intussusception is to achieve non-operative reduction and therefore patient cure.
      The standard non-surgical treatment consists of enema (air or liquid media).
      OBJECTIVE: The purpose of this study is to present external manual reduction for
      paediatric ileocolic intussusception. We present a new manoeuvre that is
      standardised, simple, safe and effective for the radiologist in the non-surgical
      management of this pathology. MATERIALS AND METHODS: External manual reduction is
      performed under sedation. Execution of the manoeuvre is detailed and illustrated.
      The procedure was carried out 15 times in 13 paediatric patients with idiopathic
      ileocolic intussusception. RESULTS: Complete reduction exclusively by external
      manual reduction was accomplished on 12 occasions (80%). In the remaining three
      procedures, partial reduction to the cecum was obtained. Subsequent enema
      achieved complete reduction in two. Overall non-surgical reduction rate was 93%.
      CONCLUSION: External manual reduction is a radiation-free, safe and effective
      procedure. In case of incomplete reduction, it facilitates enema performance.
      External manual reduction incorporates and additional initial step in the non
      surgical reduction of intussusception and should be considered a first-line
      procedure.

PMID- 22875205
TI  - Safety of routine early MRI in preterm infants.
AB  - BACKGROUND: Cerebral MRI performed on preterm infants at term-equivalent 30
      weeks' gestational age (GA) is increasingly performed as part of standard
      clinical care. OBJECTIVE: We evaluated safety of these early MRI procedures.
      MATERIALS AND METHODS: We retrospectively collected data on patient safety of
      preterm infants who underwent early MRI scans. Data were collected at fixed times
      before and after the MRI scan. MRI procedures were carried out according to a
      comprehensive guideline. RESULTS: A total of 52 infants underwent an MRI scan at
      30 weeks' GA. Although no serious adverse events occurred and vital parameters
      remained stable during the procedure, minor adverse events were encountered in 26
      infants (50%). The MRI was terminated in three infants (5.8%) because of
      respiratory instability. Increased respiratory support within 24 h after the MRI
      was necessary for 12 infants (23.1%) and was significantly associated with GA,
      birth weight and the mode of respiratory support. Hypothermia (core temperature <
      36 degrees C) occurred in nine infants (17.3%). Temperature dropped significantly
      after the MRI scan. CONCLUSION: Minor adverse events after MRI procedures at 30
      weeks GA were common and should not be underestimated. A dedicated and
      comprehensive guideline for MRI procedures in preterm infants is essential.

PMID- 22875206
TI  - Left ventricle volume measured by cardiac CT in an infant with a small left
      ventricle: a new and accurate method in determining uni- or biventricular repair.
AB  - Left ventricle volume is a factor in determining the type of surgical treatment
      in patients with a hypoplastic left ventricle. The volume of the hypoplastic left
      ventricle can be measured by echocardiography and cardiac MRI. In an infant with
      congenital heart disease and a small left ventricle, cardiac CT was used for this
      measurement and biventricular repair was performed. The left ventricular end
      diastolic volume index showed a gradual increase from 23.2 to 47.9 ml/m(2) 4
      months after the biventricular repair, and the postoperative outcome was
      excellent. Cardiac CT provided an accurate volume of the hypoplastic left
      ventricle in this infant with congenital heart disease; that volume was used to
      determine the type of surgical repair.

PMID- 22875208
TI  - An unspoken need.

PMID- 22875207
TI  - External manual reduction of paediatric idiopathic ileocolic intussusception with
      ultrasound assistance.

PMID- 22875209
TI  - Health impact of smoking and smoking  cessation strategies: current evidence.
AB  - Smoking continues to be the main preventable cause of death in the UK. Tobacco
      consumption causes a wide range of diseases and other adverse effects, including
      multiple types of cancer, chronic obstructive pulmonary disease, cardiovascular
      disease, pregnancy complications, cataracts and osteoporosis. The Government's
      vision to 'make every contact count' emphasises community nurses' responsibility
      and key potential to promote healthier living and behaviour. This article reviews
      the latest evidence on supporting smokers in practice and argues that nurses
      working in the community are ideally placed to record smoking status, give
      advice, encouragement and support, refer people to local smoking cessation
      services and offer pharmacological treatment.

PMID- 22875210
TI  - Faecal incontinence in the elderly: issues and interventions in the home.
AB  - This paper discusses current evidence-based guidelines for the management of
      faecal incontinence in the elderly. The key aspects of maintaining dignity,
      quality of life and self-esteem are addressed within a presentation of good
      assessment, prevention, management and treatment principles. Particular focus is
      given to the added problems that faecal incontinence may bring to the elderly
      person suffering with this debilitating, and often embarrassing condition. The
      increased risk to skin integrity is discussed, with reference to available
      guidance to help nurses manage the risk of skin breakdown associated with
      persistent faecal incontinence.

PMID- 22875211
TI  - Communicating with dying patients:  a time to listen more than talk.
AB  - Effective communication is central to showing empathy at the end of someone's
      life, yet it is also perhaps the most difficult skill to get right. As a result,
      communication is one of the aspects of care that patients most often complain
      about (Healthcare Commission, 2007). It is widely accepted that effective
      communication is resource and time-intensive, although the benefits tend to
      outweigh these perceived drawbacks. More importantly, poor communication can have
      an impact on patients' decision-making in preparation for death.

PMID- 22875212
TI  - The role of psychological factors  in inflammatory bowel disease.
AB  - Evidence-based practice is one of the cornerstones of contemporary community
      nursing, and conflicting research evidence can therefore have serious
      implications for nurses' decision-making. A debate about the role of
      psychological factors in inflammatory bowel disease (IBD) has been going for over
      80 years without reaching consensus and is cause for concern among clinicians.
      This article discusses the barriers to reaching consensus in the debate about the
      role of psychological factors in IBD, and why reaching a consensus to this debate
      is important for practitioners supporting IBD patients in the community. The aim
      is to raise awareness among community nurses when making sense of the
      contradictory evidence. The absence of clear and consistent research or
      guidelines can make it difficult to carry out evidence-based practice, and
      patient-centred care based on individual assessment of every person presenting
      with symptoms of IBD becomes even more important.

PMID- 22875213
TI  - Practice development: implementing  a change of practice as a team.
AB  - Practice development (PD), as a framework for multiprofessional working, has
      immense potential, specifically within change management and the clinical
      governance agenda. It has been acknowledged as a vehicle for 'continuous
      improvement'. This article discusses PD through collaborative working using the
      example of a case study on change of practice in falls reduction within a
      localised community setting. The process is underpinned by a PD framework and
      facilitated by leaders of PD within a university setting. The article identifies
      that PD frameworks are conducive to developing leadership and management roles
      within a democratic process. The article discusses the potential for
      multiprofessional PD within the locality and further afield.

PMID- 22875214
TI  - The 'Silver Book' on elderly care in  hospitals and community settings.
AB  - The number of people aged 85 and over is set to increase by two-thirds in the
      next 20 years, making it imperative that appropriate structures are in place and
      guidance is available for clinicians in every setting on best practice in caring
      for older people over the first 24 hours of an urgent care episode. This article
      discusses the launch of the Silver Book, which recommends ways in which emergency
      admissions can be reduced and the experience of those admitted improved.

PMID- 22875215
TI  - Nursing's finest hour: part 2 Queen's Nurses in the First World War.

PMID- 22875216
TI  - Optimising productivity, quality and efficiency in community nursing.
AB  - By 2014 the NHS is expected to make L21 billion in efficiency savings and
      increase productivity by 6% per annum, while maintaining or improving the quality
      of care. Given that the cost of the 1.7 million strong workforce represents 60%
      of the NHS budget, changes are likely. This context of innovation and cost
      effectiveness has resulted in an ever greater emphasis to fully engage and
      support community nursing.

PMID- 22875217
TI  - Protection of Freedoms Act 2012:  safeguarding vulnerable groups.
AB  - In last month's article on changes to the law protecting vulnerable adults from
      harm by health and social care professionals, Richard Griffith and Cassam Tengnah
      discussed changes to be made to Criminal Records Bureau checks. This month's
      article discusses the changes to the vetting and barring scheme to be introduced
      under the Protection of Freedoms Act 2012, which mean that people currently
      working in regulated activities with vulnerable groups, such as district nurses,
      will no longer need to register and be monitored by the independent safeguarding
      authority or its replacement, the Disclosure and Barring Service.

PMID- 22875218
TI  - Loneliness in old age.

PMID- 22875219
TI  - Is family functioning and communication associated with health-related quality of
      life for Chinese- and Korean-American breast cancer survivors?
AB  - PURPOSE: This study aims to investigate direct and indirect pathways of family
      flexibility, social support, and family communication on health-related quality
      of life (HRQOL) for Chinese- and Korean-American breast cancer survivors (BCS).
      METHODS: A total of 157 Chinese (n = 86)- and Korean-American (n = 71) BCS were
      recruited from the California Cancer Surveillance Program and area hospitals in
      Los Angeles County. The present study was guided by the Resiliency Model of
      Family Stress, Adjustment, and Adaptation. RESULTS: Structural equation modeling
      demonstrated that (1) family communication was directly associated with HRQOL for
      both groups; (2) family flexibility was indirectly associated with HRQOL through
      family communication for Korean-Americans only; (3) social support mediated the
      relationship between family flexibility and family communication for Chinese
      Americans only; and (4) acculturation was directly related to social support for
      both groups. Multigroup analysis demonstrated that the structural paths were
      equivalent between Chinese- and Korean-American BCS, although statistical
      differences in baseline parameters were noted. CONCLUSIONS: Our findings suggest
      that family communication impacts HRQOL among Asian-American BCS. Our results
      show that while there are commonalities in family characteristics among Asian
      Americans, specific ethnic variations also exist. Therefore, specific cultural
      and familial contexts should be assessed to better inform interventions to
      enhance family communication strategies and improve HRQOL.

PMID- 22875222
TI  - Relationship quality and levels of depression and anxiety in a large population
      based survey.
AB  - PURPOSE: There is substantial literature suggesting that the mental health
      benefits of marriage (compared to being single) are greater for those in 'good
      quality' relationships in comparison to those in 'poor-quality' relationships.
      However, little of this research utilises large population-based surveys. Large
      surveys in psychiatric epidemiology have focused almost exclusively on the
      association between marital status and mental health. The current study explores
      some of the reasons for this gap in the literature, and adopts a large,
      representative community-based sample to investigate whether associations between
      relationship status and levels of depression and anxiety are moderated by
      relationship quality. METHODS: Participants were from Wave 3 of the PATH Survey,
      a longitudinal community survey assessing the health and well-being of residents
      of the Canberra region, Australia (n = 3,820). Relationship quality was measured
      using the 7 item dyadic adjustment scale (DAS-7), and levels of depression and
      anxiety were measured using the Goldberg scales. RESULTS: Both cross-sectional
      and prospective analyses showed that associations between relationship status and
      mental health were moderated by relationship quality for both men and women, such
      that only good-quality relationships bestowed mental health benefits over
      remaining single. For women, being in a poor-quality relationship was associated
      with greater levels of anxiety than being single. CONCLUSIONS: Epidemiological
      studies need to measure relationship quality to qualify the effect of
      relationship status on mental health.

PMID- 22875223
TI  - Prognostic significance of lymph node ratio in patients undergoing
      abdominoperineal resection of rectum.
AB  - BACKGROUND: Lymph node ratio (LNR) has been shown to be an independent prognostic
      factor in stage III colorectal cancer. Abdominoperineal resection (APR) of rectum
      is historically associated with poorer oncological outcomes compared to other
      colorectal resections, and significance of LNR in this group of patients has not
      been studied. OBJECTIVE: Our aim was to determine impact of LNR on oncological
      outcomes in a series of patients with rectal cancers undergoing APR. PATIENTS AND
      METHODS: A series of patients who had undergone APR and had lymph node metastasis
      were identified from a prospectively maintained clinical, histopathological and
      radiological database. LNR was calculated, and Cox regression was used to
      determine the impact of factors affecting local recurrence, distal metastases and
      overall survival. RESULTS: Fifty-eight (42 males) patients were identified to
      have rectal cancer with lymph node involvement. LNR was an independent predictor
      of distal metastasis and overall survival at cutoff levels of 0.17, 0.41 and
      0.69. CONCLUSION: Lymph node ratio is an independent predictor of survival
      outcomes in patients with stage III tumours undergoing APR. LNR may help improve
      stratification of this group of patients.

PMID- 22875224
TI  - Treatment options for postoperatively infected abdominal wall wounds healing by
      secondary intention.
AB  - PURPOSE: We present our current clinical approach for the treatment of
      postoperatively infected wounds of the abdominal wall healing by secondary
      intention that may help in the design of a randomized controlled trial to develop
      a standardized wound treatment pathway. METHODS: Patients with postoperatively
      infected abdominal wounds treated with either Advanced Wound Care (AWC) dressings
      or vacuum-assisted closure (VAC) therapy were enrolled in the study. Follow-up
      was carried out prospectively for wound healing and incidence of incisional
      hernia at the earliest 3 years after surgery. RESULTS: Sixty-two patients were
      included and wounds were initially treated antiseptically for 5.19 +/- 2.91 days.
      Prior to VAC therapy, AWC dressings were applied for 8.75 +/- 2.93 days to reduce
      reinfection. Greater wound size (>12 * 6 * 6cm) and extensive secretion (>200
      ml/day) argued for the VAC system. Overall incidence of incisional hernia was
      20.4%, with 18.4% occurring in AWC-treated patients and 27.3% in VAC-treated
      patients. Based on these results, a wound treatment pathway was established in
      our department. CONCLUSION: The established wound treatment pathway has helped to
      increase both workflow efficacy and outcome in the treatment of abdominal wounds.
      Wound size, amount of secretion, and status of infection were the parameters we
      used for the determination of appropriate treatment. The observational data
      gathered during the initiation of our pathway lay the basis for future randomized
      controlled trials that will determine the most appropriate treatment options in
      the setting of a standardized wound treatment pathway.

PMID- 22875225
TI  - Alternative markers of hyperglycemia and risk of diabetes.
AB  - OBJECTIVE: Fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are
      of interest for monitoring short-term glycemic control in patients with diabetes;
      however, their associations with diabetes risk are uncharacterized. RESEARCH
      DESIGN AND METHODS: We used Cox proportional hazards models to examine the
      associations of fructosamine, glycated albumin, and 1,5-AG with incident diabetes
      in 1,299 participants, from the Atherosclerosis Risk in Communities (ARIC) Study
      (2005-2006), who had no history of diagnosed diabetes at baseline. Incident
      diabetes was self-reported during annual telephone calls. RESULTS: There were 119
      new cases of diabetes during a median follow-up of 3.3 years. When compared with
      the lowest quartile, the fourth quartiles of fructosamine and glycated albumin
      were significantly associated with diabetes risk (hazard ratio [HR] 3.99 [95% CI
      1.93-8.28] and 5.22 [2.49-10.94], respectively). The fourth quartile of 1,5-AG
      was associated with a significantly lower diabetes risk (0.27 [0.14-0.55]).
      Associations were attenuated but still significant after adjustment for
      hemoglobin A(1c) (A1C) or fasting glucose. CONCLUSIONS: Fructosamine, glycated
      albumin, and 1,5-AG were associated with the subsequent development of diabetes
      independently of baseline A1C and fasting glucose. Our results suggest these
      alternative biomarkers may be useful in identifying persons at risk for diabetes.

PMID- 22875226
TI  - Progression of vascular calcification is increased with statin use in the
      Veterans Affairs Diabetes Trial (VADT).
AB  - OBJECTIVE: To determine the effect of statin use on progression of vascular
      calcification in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS: Progression
      of coronary artery calcification (CAC) and abdominal aortic artery calcification
      (AAC) was assessed according to the frequency of statin use in 197 participants
      with T2DM. RESULTS: After adjustment for baseline CAC and other confounders,
      progression of CAC was significantly higher in more frequent statin users than in
      less frequent users (mean +/- SE, 8.2 +/- 0.5 mm(3) vs. 4.2 +/- 1.1 mm(3); P <
      0.01). AAC progression was in general not significantly increased with more
      frequent statin use; in a subgroup of participants initially not receiving
      statins, however, progression of both CAC and AAC was significantly increased in
      frequent statin users. CONCLUSIONS: More frequent statin use is associated with
      accelerated CAC in T2DM patients with advanced atherosclerosis.

PMID- 22875227
TI  - A learner-centered diabetes management curriculum: reducing resident errors on an
      inpatient diabetes pathway.
AB  - OBJECTIVE: Diabetes errors, particularly insulin administration errors, can lead
      to complications and death in the pediatric inpatient setting. Despite a lecture
      format curriculum on diabetes management at our children's hospital, resident
      diabetes-related errors persisted. We hypothesized that a multifaceted, learner
      centered diabetes curriculum would help reduce pathway errors. RESEARCH DESIGN
      AND METHODS: The 8-week curricular intervention consisted of 1) an online
      tutorial addressing residents' baseline diabetes management knowledge, 2) an
      interactive diabetes pathway discussion, 3) a learner-initiated diabetes question
      and answer session, and 4) a case presentation featuring embedded pathway errors
      for residents to recognize, resolve, and prevent. Errors in the 9 months before
      the intervention, as identified through an incident reporting system, were
      compared with those in the 10 months afterward, with errors classified as
      relating to insulin, communication, intravenous fluids, nutrition, and discharge
      delay. RESULTS: Before the curricular intervention, resident errors occurred in
      28 patients (19.4% of 144 diabetes admissions) over 9 months. After the
      intervention, resident errors occurred in 11 patients (6.6% of 166 diabetes
      admissions) over 10 months, representing a statistically significant (P = 0.0007)
      decrease in patients with errors from before intervention to after intervention.
      Throughout the study, the errors were distributed into the categories as follows:
      insulin, 43.8%; communication, 39.6%; intravenous fluids, 14.6%; nutrition, 0%;
      and discharge delay, 2.1%. CONCLUSIONS: An interactive learner-centered diabetes
      curriculum for pediatric residents can be effective in reducing inpatient
      diabetes errors in a tertiary children's hospital. This educational model
      promoting proactive learning has implications for decreasing errors across other
      medical disciplines.

PMID- 22875228
TI  - Traditional risk factors alone could not explain the excess mortality in patients
      with diabetes: a national cohort study of older Spanish adults.
AB  - OBJECTIVE: Individuals with diabetes have an excess mortality compared with
      people without diabetes. This study used a national cohort of older Spanish
      adults to identify possible factors explaining the relation between diabetes and
      excess mortality. RESEARCH DESIGN AND METHODS: A cohort of 4,008 people >=60
      years of age was selected in 2000-2001 and followed prospectively until 2008. At
      baseline, data were collected on diabetes and major risk factors for mortality:
      social network, diet, physical activity and other lifestyle factors, obesity,
      hypertension, dyslipidemia, and previous cardiovascular disease and cancer.
      Analyses were conducted with Cox regression with progressive adjustment for
      mortality risk factors. RESULTS: In the study cohort, 667 people had diabetes. A
      total of 972 deaths occurred during follow-up. The hazard ratio (HR) and 95% CI
      for mortality in diabetic versus nondiabetic subjects, adjusted for age, marital
      status, education level, social class, medical consultation, and treatment with
      statins, angiotensin II antagonists, or aspirin, was 1.40 (1.11-1.76) in men and
      1.70 (1.37-2.10) in women. Adjustment for additional risk factors produced little
      change in the HR. After adjustment for all risk factors, including cardiovascular
      disease and cancer, the mortality HR in diabetic versus nondiabetic individuals
      was 1.43 (1.12-1.82) in men and 1.67 (1.34-2.08) in women. The inclusion of
      lifestyles and diseases occurring during follow-up also produced little change in
      the relation between diabetes and mortality. CONCLUSIONS: The excess risk of
      mortality in diabetic versus nondiabetic individuals cannot be explained by
      mortality risk factors or by the presence of cardiovascular disease or cancer.

PMID- 22875229
TI  - Sudden cardiac death after myocardial infarction in type 2 diabetic patients with
      no residual myocardial ischemia.
AB  - OBJECTIVE: Diabetes mellitus (DM) is a well-established risk factor for coronary
      artery disease. Nonetheless, it remains unclear whether DM contributes to sudden
      cardiac death in patients who survive myocardial infarction (MI). The objective
      of this study was to compare the incidence of sudden cardiac death post-MI in
      diabetic and nondiabetic patients with no residual myocardial ischemia. RESEARCH
      DESIGN AND METHODS: A total of 610 consecutive post-MI patients referred to a
      cardiac rehabilitation program with negative exercise stress test were studied.
      RESULTS: Of these, 236 patients had DM at baseline. Over a mean follow-up of 5
      years, 67 patients with DM (28.4%) and 76 of 374 patients without DM (20.2%) had
      died with a hazard ratio (HR) of 1.74 (95% CI: 1.28-2.56; P < 0.001). Patients
      with DM also had a higher incidence of cardiac death (1.84 [1.16-3.21]; P =
      0.01), principally due to a higher incidence of sudden cardiac death (2.14 [1.22
      4.23]; P < 0.001). Multiple Cox regression analysis revealed that only DM
      (adjusted HR: 1.9 [95% CI: 1.04-3.40]; P = 0.04), left ventricular ejection
      fraction (LVEF) <=30% (3.6 [1.46-8.75]; P < 0.01), and New York Heart Association
      functional class >II (4.2 [1.87-9.45]; P < 0.01) were independent predictors for
      sudden cardiac death. Among patients with DM, the 5-year sudden cardiac death
      rate did not differ significantly among those with LVEF <=30%, LVEF 31-50%, or
      LVEF >50% (8.8 vs. 7.8 vs. 6.8%, respectively; P = 0.83). CONCLUSIONS: Post-MI
      patients with DM, even in the absence of residual myocardial ischemia clinically,
      were at higher risk of sudden cardiac death than their non-DM counterparts.

PMID- 22875230
TI  - The use of an automated, portable glucose control system for overnight glucose
      control in adolescents and young adults with type 1 diabetes.
AB  - OBJECTIVE: A key milestone in progress towards providing an efficacious and safe
      closed-loop artificial pancreas system for outpatient use is the development of
      fully automated, portable devices with fault detection capabilities to ensure
      patient safety. The ability to remotely monitor the operation of the closed-loop
      system would facilitate future physician-supervised home studies. RESEARCH DESIGN
      AND METHODS: This study was designed to investigate the efficacy and safety of a
      fully automated, portable, closed-loop system. The Medtronic Portable Glucose
      Control System (PGCS) consists of two subcutaneous glucose sensors, a control
      algorithm based on proportional-integral-derivative with insulin feedback
      operating from a BlackBerry Storm smartphone platform, Bluetooth radiofrequency
      translator, and an off-the-shelf Medtronic Paradigm Veo insulin pump.
      Participants with type 1 diabetes using insulin pump therapy underwent two
      consecutive nights of in-clinic, overnight, closed-loop control after a baseline
      open-loop assessment. RESULTS: Eight participants attended for 16 overnight
      studies. The PGCS maintained mean overnight plasma glucose levels of 6.4 +/- 1.7
      mmol/L (115 +/- 31 mg/dL). The proportion of time with venous plasma glucose
      <3.9, between 3.9 and 8 (70 and 144 mg/dL), and >8 mmol/L was 7, 78, and 15%,
      respectively. The proportion of time the sensor glucose values were maintained
      between 3.9 and 8 mmol/L was greater for closed-loop than open-loop (84.5 vs.
      46.7%; P < 0.0001), and time spent <3.3 mmol/L was also reduced (0.9 vs. 3%; P <
      0.0001). CONCLUSIONS: These results suggest that the PGCS, an automated closed
      loop device, is safe and effective in achieving overnight glucose control in
      patients with type 1 diabetes.

PMID- 22875231
TI  - The effect of walking on postprandial glycemic excursion in patients with type 1
      diabetes and healthy people.
AB  - OBJECTIVE: Physical activity (PA), even at low intensity, promotes health and
      improves hyperglycemia. However, the effect of low-intensity PA captured with
      accelerometery on glucose variability in healthy individuals and patients with
      type 1 diabetes has not been examined. Quantifying the effects of PA on glycemic
      variability would improve artificial endocrine pancreas (AEP) algorithms.
      RESEARCH DESIGN AND METHODS: We studied 12 healthy control subjects (five males,
      37.7 +/- 13.7 years of age) and 12 patients with type 1 diabetes (five males,
      37.4 +/- 14.2 years of age) for 88 h. Participants performed PA approximating a
      threefold increase over their basal metabolic rate. PA was captured using a PA
      monitoring system, and interstitial fluid glucose concentrations were captured
      with continuous glucose monitors. In random order, one meal per day was followed
      by inactivity, and the other meals were followed by walking. Glucose and PA data
      for a total of 216 meals were analyzed from 30 min prior to meal ingestion to 270
      min postmeal. RESULTS: In healthy subjects, the incremental glucose area under
      the curve was 4.5 mmol/L/270 min for meals followed by walking, whereas it was
      9.6 mmol/L/270 min (P = 0.022) for meals followed by inactivity. The
      corresponding glucose excursions for those with type 1 diabetes were 7.5
      mmol/L/270 min and 18.4 mmol/L/270 min, respectively (P < 0.001). CONCLUSIONS:
      Walking significantly impacts postprandial glucose excursions in healthy
      populations and in those with type 1 diabetes. AEP algorithms incorporating PA
      may enhance tight glycemic control end points.

PMID- 22875232
TI  - Estimation of expected life-years saved from successful prevention of end-stage
      renal disease in elderly patients with diabetes: a nationwide study from Taiwan.
AB  - OBJECTIVE: Because of the increasing incidence and prevalence of diabetes as a
      leading cause of end-stage renal disease (ESRD) in the aging population, we
      estimated the expected life-years (LYs) saved from successful prevention of ESRD
      in elderly patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted a
      population-based cohort study using the National Health Insurance Research
      Database. We identified all incidences of ESRD in the individuals >65 years of
      age who were receiving maintenance hemodialysis (N = 24,243) from the registry
      files of catastrophic illnesses in Taiwan from 1 July 1997 to 31 December 2005.
      We then retrospectively searched the database to determine whether there had been
      a diagnosis of diabetes in these cases. After the exclusion of individuals with
      malignancy (n = 3,423), we extrapolated the survival rates through the end of
      2006 using the Monte Carlo method. Using the data of preventable ESRD cases due
      to diabetes and expected years of life lost (EYLL) in each age stratum, we
      further estimated the expected LYs saved from successful prevention of ESRD in
      elderly patients with diabetes. RESULTS: The estimated average EYLL was 10.6-5.8
      and 12.3-7.3 years for diabetic males and females, respectively, aged 65-79
      years. In total, 5,430.1 LYs and 10,177 LYs could be saved by the successful
      prevention of ESRD in male and female elderly patients with diabetes,
      respectively, in a single year. CONCLUSIONS: The LYs saved by successful
      prevention of ESRD in elderly patients with diabetes in a single year are
      substantial and deserve special attention, especially in elderly females.

PMID- 22875233
TI  - beta-cell mass and turnover in humans: effects of obesity and aging.
AB  - OBJECTIVE: We sought to establish beta-cell mass, beta-cell apoptosis, and beta
      cell replication in humans in response to obesity and advanced age. RESEARCH
      DESIGN AND METHODS: We examined human autopsy pancreas from 167 nondiabetic
      individuals 20-102 years of age. The effect of obesity on beta-cell mass was
      examined in 53 lean and 61 obese subjects, and the effect of aging was examined
      in 106 lean subjects. RESULTS: beta-Cell mass is increased by ~50% with obesity
      (from 0.8 to 1.2 g). With advanced aging, the exocrine pancreas undergoes atrophy
      but beta-cell mass is remarkably preserved. There is minimal beta-cell
      replication or apoptosis in lean humans throughout life with no detectable
      changes with obesity or advanced age. CONCLUSIONS: beta-Cell mass in human
      obesity increases by ~50% by an increase in beta-cell number, the source of which
      is unknown. beta-Cell mass is well preserved in humans with advanced aging.

PMID- 22875234
TI  - Factors associated with never being screened for colorectal cancer.
AB  - Colorectal cancer (CRC) screening is underused in the United States, and non
      adherence with screening recommendations is high in some populations. This study
      describes the characteristics of people who have never been screened for CRC. In
      addition, we use the health belief model to examine the constructs associated
      with screening behavior. We used data from the 2010 Behavioral Risk Factor
      Surveillance System (BRFSS) to create three study outcomes: people who have been
      screened for CRC and are up-to-date with current recommendations, people who have
      been screened but are not up-to-date, and people who have never been screened. We
      used multivariate logistic regression modeling to calculate predicted marginal
      estimates examining the associations between the screening outcomes and
      demographic and Health Belief Model (HBM) characteristics. Overall 29% of
      respondents had never been screened for CRC. In the adjusted model, 36.6% of US
      adults age 50-59 years and 29.1% of US men reported never being screened for CRC.
      More Asian/Native Hawaiian/Pacific Islander, non-Hispanics (38.2%) reported never
      being screened than members of other racial and ethnic groups. Nearly 37% of
      people with less than a high school diploma reported never being screened. We
      found statistically significant differences among screening outcomes for all
      demographics and HBM constructs except could not see a doctor because of costs in
      the last 12 months, where approximately 29% reported no CRC screening. New
      interventions should focus on those subpopulations that have never been screened
      for CRC.

PMID- 22875235
TI  - Unheard voices: a qualitative exploration of fathers' access of child safety
      information.
AB  - To gain an understanding about fathers' perspectives and practices related to
      accessing information on childhood safety. Qualitative interviews were carried
      out with 32 fathers of children aged 2-7 years in British Columbia, Canada.
      Interview questions investigated whether fathers accessed information on child
      safety issues, the type of information they searched for, and the resources they
      used. Transcripts were examined using thematic content analysis. Fathers reported
      varied processes for searching for information and emphasized a need for
      credible, synthesized information. The internet was the source of child safety
      information fathers mentioned most frequently. Published information, resources
      from community organizations including general, educational and health
      organizations and access to personal connections were also seen as important.
      Fathers' involvement in childcare is growing and they play a significant role in
      ensuring children's safety. Increasing fathers' knowledge on safety related
      practices can contribute to a reduction in childhood injuries. The results of
      this study provide an in-depth exploration of fathers' perspectives and practices
      that can inform the design of materials and dissemination strategies to help
      increase and optimize access to safety information.

PMID- 22875236
TI  - Mobile voice health monitoring using a wearable accelerometer sensor and a
      smartphone platform.
AB  - Many common voice disorders are chronic or recurring conditions that are likely
      to result from faulty and/or abusive patterns of vocal behavior, referred to
      generically as vocal hyperfunction. An ongoing goal in clinical voice assessment
      is the development and use of noninvasively derived measures to quantify and
      track the daily status of vocal hyperfunction so that the diagnosis and treatment
      of such behaviorally based voice disorders can be improved. This paper reports on
      the development of a new, versatile, and cost-effective clinical tool for mobile
      voice monitoring that acquires the high-bandwidth signal from an accelerometer
      sensor placed on the neck skin above the collarbone. Using a smartphone as the
      data acquisition platform, the prototype device provides a user-friendly
      interface for voice use monitoring, daily sensor calibration, and periodic alert
      capabilities. Pilot data are reported from three vocally normal speakers and
      three subjects with voice disorders to demonstrate the potential of the device to
      yield standard measures of fundamental frequency and sound pressure level and
      model-based glottal airflow properties. The smartphone-based platform enables
      future clinical studies for the identification of the best set of measures for
      differentiating between normal and hyperfunctional patterns of voice use.

PMID- 22875237
TI  - A wireless portable system with microsensors for monitoring respiratory diseases.
AB  - A wireless portable monitoring system for respiratory diseases using microsensors
      is proposed. The monitoring system consists of two sensor nodes integrating with
      Bluetooth transmitters that measure user's respiratory airflow, blood oxygen
      saturation, and body posture. The utility of micro-hot-film flow sensor makes the
      monitor can acquire comprehensive respiration parameters which are useful for
      diagnoses of obstructive sleep apnea, chronic obstructive pulmonary disease, and
      asthma. The system can serve as both sleep recorder and spirometer. Additionally,
      a mobile phone or a PC connected to the Internet serving as a monitoring and
      transfer terminal makes telemedicine achievable. Several experiments were
      conducted to verify the feasibility and effectiveness of the proposed system for
      monitoring and diagnosing OSA, COPD, and asthma.

PMID- 22875238
TI  - Robust human activity and sensor location corecognition via sparse signal
      representation.
AB  - Human activity recognition with wearable body sensors receives lots of attentions
      in both research and industrial communities due to the significant role in
      ubiquitous and mobile health monitoring. One of the most concerned issues related
      to this wearable technology is that the sensor signals significantly depends on
      where the sensors are worn on the human body. Existing research work either
      extracts location information from the activity signals or takes advantage of the
      sensor location information as  a priori information to achieve better activity
      recognition performance. In this paper, we present a sparse signal-based approach
      to corecognize human activity and sensor location in a single framework.
      Therefore, the wearable sensor is not necessarily constrained to fixed body
      position and the deployment is much easier although the recognition difficulty
      becomes much more challenging. To validate the effectiveness of our approach, we
      run a pilot study in the lab, which includes 14 human activities and seven on
      body locations to recognize. The experimental results show that our approach
      achieves an 87.72% classification accuracy (the mean of precision and recall),
      which outperforms classical classification methods.

PMID- 22875239
TI  - A real-time automated point-process method for the detection and correction of
      erroneous and ectopic heartbeats.
AB  - The presence of recurring arrhythmic events (also known as cardiac dysrhythmia or
      irregular heartbeats), as well as erroneous beat detection due to low signal
      quality, significantly affects estimation of both time and frequency domain
      indices of heart rate variability (HRV). A reliable, real-time classification and
      correction of ECG-derived heartbeats is a necessary prerequisite for an accurate
      online monitoring of HRV and cardiovascular control. We have developed a novel
      point-process-based method for real-time R-R interval error detection and
      correction. Given an R-wave event, we assume that the length of the next R-R
      interval follows a physiologically motivated, time-varying inverse Gaussian
      probability distribution. We then devise an instantaneous automated detection and
      correction procedure for erroneous and arrhythmic beats by using the information
      on the probability of occurrence of the observed beat provided by the model. We
      test our algorithm over two datasets from the PhysioNet archive. The Fantasia
      normal rhythm database is artificially corrupted with known erroneous beats to
      test both the detection procedure and correction procedure. The benchmark MIT-BIH
      Arrhythmia database is further considered to test the detection procedure of real
      arrhythmic events and compare it with results from previously published
      algorithms. Our automated algorithm represents an improvement over previous
      procedures, with best specificity for the detection of correct beats, as well as
      highest sensitivity to missed and extra beats, artificially misplaced beats, and
      for real arrhythmic events. A near-optimal heartbeat classification and
      correction, together with the ability to adapt to time-varying changes of
      heartbeat dynamics in an online fashion, may provide a solid base for building a
      more reliable real-time HRV monitoring device.

PMID- 22875240
TI  - Time-frequency analysis of the endocavitarian signal in paroxysmal atrial
      fibrillation.
AB  - We apply the time-frequency analysis to the endocavitarian signal of patients
      suffering from paroxysmal atrial fibrillation. The time-frequency spectrum
      reveals the components of the endocavitarian signal. These components are located
      in the regions of the time-frequency domain that differ for in-rhythm and in
      atrial fibrillation signals. By using experimental data, we perform a statistical
      study of these regions, and we obtain their average value. The difference in the
      shape of these regions is caused by the re-entry circuits that characterize
      atrial fibrillation. We propose a propagation model for atrial fibrillation based
      on the re-entry circuits, which explains the shape of the time-frequency
      spectrum.

PMID- 22875241
TI  - Encapsulation and release of aqueous components from sonochemically produced
      protein microspheres.
AB  - Aqueous solutions of salts or dyes have been contained in sonochemically produced
      lysozyme microspheres by encapsulating an inverse emulsion in tetradecane.
      Release can be triggered by chemically disrupting crosslinking in the protein
      shell or by mechanical disruption using high intensity ultrasound.

PMID- 22875243
TI  - Patient specific prostate segmentation in 3-d magnetic resonance images.
AB  - Accurate localization of the prostate and its surrounding tissue is essential in
      the treatment of prostate cancer. This paper presents a novel approach to fully
      automatically segment the prostate, including its seminal vesicles, within a few
      minutes of a magnetic resonance (MR) scan acquired without an endorectal coil.
      Such MR images are important in external beam radiation therapy, where using an
      endorectal coil is highly undesirable. The segmentation is obtained using a
      deformable model that is trained on-the-fly so that it is specific to the
      patient's scan. This case specific deformable model consists of a patient
      specific initialized triangulated surface and image feature model that are
      trained during its initialization. The image feature model is used to deform the
      initialized surface by template matching image features (via normalized cross
      correlation) to the features of the scan. The resulting deformations are
      regularized over the surface via well established simple surface smoothing
      algorithms, which is then made anatomically valid via an optimized shape model.
      Mean and median Dice's similarity coefficients (DSCs) of 0.85 and 0.87 were
      achieved when segmenting 3T MR clinical scans of 50 patients. The median DSC
      result was equal to the inter-rater DSC and had a mean absolute surface error of
      1.85 mm. The approach is showed to perform well near the apex and seminal
      vesicles of the prostate.

PMID- 22875242
TI  - Therapeutic strategies for harnessing human eosinophils in allergic inflammation,
      hypereosinophilic disorders, and cancer.
AB  - The eosinophil is a multifunctional granulocyte best known for providing host
      defense against parasites. Paradoxically, eosinophils are also implicated in the
      pathogenesis of allergic inflammation, asthma, and hypereosinophilic syndromes.
      Emerging evidence also supports the potential for harnessing the cytotoxic power
      of eosinophils and redirecting it to kill solid tumors. Central to eosinophil
      physiology is interleukin-5 (IL-5) and its receptor (IL-5R) which is composed of
      a ligand-specific alpha chain (IL-5Ralpha) and the common beta chain (betac).
      Eosinophil activation can lead to their degranulation, resulting in rapid release
      of an arsenal of tissue-destructive proinflammatory mediators and cytotoxic
      proteins that can be both beneficial and detrimental to the host. This review
      discusses eosinophil immunobiology and therapeutic strategies for targeting of IL
      5 and IL-5R, as well as the potential for harnessing eosinophil cytotoxicity as a
      tumoricide.

PMID- 22875245
TI  - 3-D adaptive nonlinear complex-diffusion despeckling filter.
AB  - This work aims to improve the process of speckle noise reduction while preserving
      edges and other relevant features through filter expansion from 2-D to 3-D.
      Despeckling is very important for data visual inspection and as a preprocessing
      step for other algorithms, as they are usually notably influenced by speckle
      noise. To that intent, a 3-D approach is proposed for the adaptive complex
      diffusion filter. This 3-D iterative filter was applied to spectral-domain
      optical coherence tomography medical imaging volumes of the human retina and a
      quantitative evaluation of the results was performed to allow a demonstration of
      the better performance of the 3-D over the 2-D filtering and to choose the best
      total diffusion time. In addition, we propose a fast graphical processing unit
      parallel implementation so that the filter can be used in a clinical setting.

PMID- 22875244
TI  - Penalized likelihood PET image reconstruction using patch-based edge-preserving
      regularization.
AB  - Iterative image reconstruction for positron emission tomography (PET) can improve
      image quality by using spatial regularization that penalizes image intensity
      difference between neighboring pixels. The most commonly used quadratic penalty
      often oversmoothes edges and fine features in reconstructed images. Nonquadratic
      penalties can preserve edges but often introduce piece-wise constant blocky
      artifacts and the results are also sensitive to the hyper-parameter that controls
      the shape of the penalty function. This paper presents a patch-based
      regularization for iterative image reconstruction that uses neighborhood patches
      instead of individual pixels in computing the nonquadratic penalty. The new
      regularization is more robust than the conventional pixel-based regularization in
      differentiating sharp edges from random fluctuations due to noise. An
      optimization transfer algorithm is developed for the penalized maximum likelihood
      estimation. Each iteration of the algorithm can be implemented in three simple
      steps: an EM-like image update, an image smoothing and a pixel-by-pixel image
      fusion. Computer simulations show that the proposed patch-based regularization
      can achieve higher contrast recovery for small objects without increasing
      background variation compared with the quadratic regularization. The
      reconstruction is also more robust to the hyper-parameter than conventional pixel
      based nonquadratic regularizations. The proposed regularization method has been
      applied to real 3-D PET data.

PMID- 22875247
TI  - Multiscale distance matrix for fast plant leaf recognition.
AB  - In this brief, we propose a novel contour-based shape descriptor, called the
      multiscale distance matrix, to capture the shape geometry while being invariant
      to translation, rotation, scaling, and bilateral symmetry. The descriptor is
      further combined with a dimensionality reduction to improve its discriminative
      power. The proposed method avoids the time-consuming pointwise matching
      encountered in most of the previously used shape recognition algorithms. It is
      therefore fast and suitable for real-time applications. We applied the proposed
      method to the task of plan leaf recognition with experiments on two data sets,
      the Swedish Leaf data set and the ICL Leaf data set. The experimental results
      clearly demonstrate the effectiveness and efficiency of the proposed descriptor.

PMID- 22875248
TI  - Optimizing the error diffusion filter for blue noise halftoning with multiscale
      error diffusion.
AB  - A good halftoning output should bear a blue noise characteristic contributed by
      isotropically-distributed isolated dots. Multiscale error diffusion (MED)
      algorithms try to achieve this by exploiting radially symmetric and noncausal
      error diffusion filters to guarantee spatial homogeneity. In this brief, an
      optimized diffusion filter is suggested to make the diffusion close to isotropic.
      When it is used with MED, the resulting output has a nearly ideal blue noise
      characteristic.

PMID- 22875246
TI  - Rapamycin inhibits both motility through down-regulation of p-STAT3 (S727) by
      disrupting the mTORC2 assembly and peritoneal dissemination in sarcomatoid
      cholangiocarcinoma.
AB  - Cholangiocarcinoma (CC) is a malignant epithelium neoplasm that originates from
      the bile epithelium and for which there are few therapeutic strategies. The mTOR
      pathway involved in many cellular processes was reported to be up-regulated in
      various cancers. We investigated the activation of the AKT/mTOR pathway in CC
      cell lines with different degrees of dedifferentiation and found that rapamycin
      could suppress the motility and the peritoneal dissemination of sarcomatoid SCK
      cells. Inhibition of the mTOR pathway with rapamycin decreased significantly the
      number of tumor nodules and prolonged the survival rates of nude mice inoculated
      with sarcomatoid CC cells. Prolonged treatments with rapamycin were found to
      disrupt the mTORC2 assembly and to reduce the phosphorylation of STAT3 at Ser
      727. Rapamycin decreased both mRNA and protein levels of MMP2 and Twist1, which
      are regulated by STAT3 and associated with cancer metastasis. The overexpression
      of STAT3 S727A lacking the phosphorylation site resulted in significantly less
      sensitivity to rapamycin than the overexpression of STAT3 WT. Taken together, our
      results suggest that rapamycin could suppress the motility of sarcomatoid CC by
      down-regulating p-STAT3 (S727) through the impairment of mTORC2 assembly.

PMID- 22875249
TI  - On preserving original variables in Bayesian PCA with application to image
      analysis.
AB  - Principal component analysis (PCA) computes a succinct data representation by
      converting the data to a few new variables while retaining maximum variation.
      However, the new variables are difficult to interpret, because each one is
      combined with all of the original input variables and has obscure semantics.
      Under the umbrella of Bayesian data analysis, this paper presents a new prior to
      explicitly regularize combinations of input variables. In particular, the prior
      penalizes pair-wise products of the coefficients of PCA and encourages a sparse
      model. Compared to the commonly used l1regularizer, the proposed prior encourages
      the sparsity pattern in the resultant coefficients to be consistent with the
      intrinsic groups in the original input variables. Moreover, the proposed prior
      can be explained as recovering a robust estimation of the covariance matrix for
      PCA. The proposed model is suited for analyzing visual data, where it encourages
      the output variables to correspond to meaningful parts in the data. We
      demonstrate the characteristics and effectiveness of the proposed technique
      through experiments on both synthetic and real data.

PMID- 22875250
TI  - Integrating graph partitioning and matching for trajectory analysis in video
      surveillance.
AB  - In order to track moving objects in long range against occlusion, interruption,
      and background clutter, this paper proposes a unified approach for global
      trajectory analysis. Instead of the traditional frame-by-frame tracking, our
      method recovers target trajectories based on a short sequence of video frames,
      e.g., 15 frames. We initially calculate a foreground map at each frame obtained
      from a state-of-the-art background model. An attribute graph is then extracted
      from the foreground map, where the graph vertices are image primitives
      represented by the composite features. With this graph representation, we pose
      trajectory analysis as a joint task of spatial graph partitioning and temporal
      graph matching. The task can be formulated by maximizing a posteriori under the
      Bayesian framework, in which we integrate the spatio-temporal contexts and the
      appearance models. The probabilistic inference is achieved by a data-driven
      Markov chain Monte Carlo algorithm. Given a period of observed frames, the
      algorithm simulates an ergodic and aperiodic Markov chain, and it visits a
      sequence of solution states in the joint space of spatial graph partitioning and
      temporal graph matching. In the experiments, our method is tested on several
      challenging videos from the public datasets of visual surveillance, and it
      outperforms the state-of-the-art methods.

PMID- 22875251
TI  - A wearable sensor module with a neural-network-based activity classification
      algorithm for daily energy expenditure estimation.
AB  - This paper presents a wearable module and neural-network-based activity
      classification algorithm for energy expenditure estimation. The purpose of our
      design is first to categorize physical activities with similar intensity levels,
      and then to construct energy expenditure regression (EER) models using neural
      networks in order to optimize the estimation performance. The classification of
      physical activities for EER model construction is based on the acceleration and
      ECG signal data collected by wearable sensor modules developed by our research
      lab. The proposed algorithm consists of procedures for data collection, data
      preprocessing, activity classification, feature selection, and construction of
      EER models using neural networks. In order to reduce the computational load and
      achieve satisfactory estimation performance, we employed sequential forward and
      backward search strategies for feature selection. Two representative neural
      networks, a radial basis function network (RBFN) and a generalized regression
      neural network (GRNN), were employed as EER models for performance comparisons.
      Our experimental results have successfully validated the effectiveness of our
      wearable sensor module and its neural-network-based activity classification
      algorithm for energy expenditure estimation. In addition, our results demonstrate
      the superior performance of GRNN as compared to RBFN.

PMID- 22875252
TI  - Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.
AB  - Given the poor prognosis of esophageal cancer and the invasiveness of combined
      modality treatment, improved prognostic scoring systems are needed. We developed
      a fuzzy logic-based system to improve the predictive performance of a risk score
      based on the serum concentrations of C-reactive protein (CRP) and albumin in a
      cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and
      multivariate survival analyses were employed to validate the independent
      prognostic value of the fuzzy risk score. To further compare the predictive
      performance of the fuzzy risk score with other prognostic scoring systems, time
      dependent receiver operating characteristic curve (ROC) analysis was used.
      Application of fuzzy logic to the serum values of CRP and albumin increased
      predictive performance for 1-year overall survival (AUC=0.773) compared with that
      of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where
      the AUC denotes the area under curve. This fuzzy logic-based approach also
      performed consistently better than the Glasgow Prognostic Score (GPS)
      (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers
      can more accurately predict the outcome for patients with esophageal cancer. 

PMID- 22875253
TI  - Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes
      from pandemic H1N1 virus.
AB  - Both H9N2 avian influenza and 2009 pandemic H1N1 viruses (pH1N1) are able to
      infect humans and swine, which has raised concerns that novel reassortant H9
      viruses with pH1N1 genes might be generated in these hosts by reassortment.
      Although previous studies have demonstrated that reassortant H9 viruses with
      pH1N1 genes show increased virulence in mice and transmissibility in ferrets, the
      virulence and transmissibility of reassortant H9 viruses in natural hosts such as
      chickens and swine remain unknown. This study generated two reassortant H9
      viruses (H9N2/CA09 and H9N1/CA09) in the background of the pH1N1
      A/California/04/2009 (CA09) virus by replacing either both the haemagglutinin
      (HA) and neuraminidase (NA) genes or only the HA gene with the respective genes
      from the A/quail/Hong Kong/G1/1997 (H9N2) virus and evaluated their replication,
      pathogenicity and transmission in chickens and pigs compared with the parental
      viruses. Chickens that were infected with the parental H9N2 and reassortant H9
      viruses seroconverted. The parental H9N2 and reassortant H9N2/CA09 viruses were
      transmitted to sentinel chickens, but H9N1/CA09 virus was not. The parental H9N2
      replicated poorly and was not transmitted in pigs, whereas both H9N2/CA09 and
      H9N1/CA09 viruses replicated and were transmitted efficiently in pigs, similar to
      the pH1N1 virus. These results demonstrated that reassortant H9 viruses with
      pH1N1 genes show enhanced replication and transmissibility in pigs compared with
      the parental H9N2 virus, indicating that they may pose a threat for humans if
      such reassortants arise in swine.

PMID- 22875254
TI  - Identification and complete genome characterization of a novel picornavirus in
      turkey (Meleagris gallopavo).
AB  - Members of the family Picornaviridae are important pathogens of humans and
      animals, although compared with the thousands of known bird species (>10 000),
      only a few (n = 11) picornaviruses have been identified from avian sources. This
      study reports the metagenomic detection and complete genome characterization of a
      novel turkey picornavirus from faecal samples collected from eight turkey farms
      in Hungary. Using RT-PCR, both healthy (two of three) and affected (seven of
      eight) commercial turkeys with enteric and/or stunting syndrome were shown to be
      shedding viruses in seven (88 %) of the eight farms. The viral genome sequence
      (turkey/M176/2011/HUN; GenBank accession no. JQ691613) shows a high degree of
      amino acid sequence identity (96 %) to the partial P3 genome region of a
      picornavirus reported recently in turkey and chickens from the USA and probably
      belongs to the same species. In the P1 and P2 regions, turkey/M176/2011/HUN is
      related most closely to, but distinct from, the kobuviruses and turdivirus 1.
      Complete genome analysis revealed the presence of characteristic picornaviral
      amino acid motifs, a potential type II-like 5' UTR internal ribosome entry site
      (first identified among avian-origin picornaviruses) and a conserved, 48 nt long
      'barbell-like' structure found at the 3' UTR of turkey/M176/2011/HUN and members
      of the picornavirus genera Avihepatovirus and Kobuvirus. The general presence of
      turkey picornavirus - a novel picornavirus species - in faecal samples from
      healthy and affected turkeys in Hungary and in the USA suggests the worldwide
      occurrence and endemic circulation of this virus in turkey farms. Further studies
      are needed to investigate the aetiological role and pathogenic potential of this
      picornavirus in food animals.

PMID- 22875255
TI  - Modulation of foot-and-mouth disease virus pH threshold for uncoating correlates
      with differential sensitivity to inhibition of cellular Rab GTPases and decreases
      infectivity in vivo.
AB  - The role of cellular Rab GTPases that govern traffic between different endosome
      populations was analysed on foot-and-mouth disease virus (FMDV) infection.
      Changes of viral receptor specificity did not alter Rab5 requirement for
      infection. However, a correlation between uncoating pH and requirement of Rab5
      for infection was observed. A mutant FMDV with less acidic uncoating pH threshold
      was less sensitive to inhibition of Rab5, whereas another mutant with more acidic
      requirements was more sensitive to inhibition of Rab5. On the contrary, opposed
      correlations between uncoating pH and dependence of Rab function were observed
      upon expression of dominant-negative forms of Rab7 or 11. Modulation of uncoating
      pH also reduced FMDV virulence in suckling mice. These results are consistent
      with FMDV uncoating inside early endosomes and indicate that displacements from
      optimum pH for uncoating reduce viral fitness in vivo.

PMID- 22875257
TI  - First isolation of an Entomobirnavirus from free-living insects.
AB  - Drosophila X virus (DXV), the prototype Entomobirnavirus, is a well-studied RNA
      virus model. Its origin is unknown, and so is that of the only other
      entomobirnavirus, Espirito Santo virus (ESV). We isolated an entomobirnavirus
      tentatively named Culex Y virus (CYV) from hibernating Culex pipiens complex
      mosquitoes in Germany. CYV was detected in three pools consisting of 11
      mosquitoes each. Full-genome sequencing and phylogenetic analyses suggested that
      CYV and ESV define one sister species to DXV within the genus Entomobirnavirus.
      In contrast to the laboratory-derived ESV, the ORF5 initiation codon AUG was
      mutated to (1927)GUG in all three wild-type CYV isolates. Also in contrast to
      ESV, replication of CYV was not dependent on other viruses in insect cell
      culture. CYV could provide a wild-type counterpart in research fields relying on
      DXV and other cell culture-adapted strains.

PMID- 22875256
TI  - Viral mitochondria-localized inhibitor of apoptosis (UL37 exon 1 protein) does
      not protect human neural precursor cells from human cytomegalovirus-induced cell
      death.
AB  - Congenital human cytomegalovirus (HCMV) infection can cause severe brain
      abnormalities. Apoptotic HCMV-infected brain cells have been detected in a
      congenitally infected infant. In biologically relevant human neural precursor
      cells (hNPCs), cultured in physiological oxygen tensions, HCMV infection (m.o.i.
      of 1 or 3) induced cell death within 3 days post-infection (p.i.) and increased
      thereafter. Surprisingly, its known anti-apoptotic genes, including the potent
      UL37 exon 1 protein (pUL37x1) or viral mitochondria-localized inhibitor of
      apoptosis (vMIA), which protects infected human fibroblasts (HFFs) from apoptosis
      and from caspase-independent, mitochondrial serine protease-mediated cell death,
      were expressed by 2 days p.i. Consistent with this finding, an HCMV UL37x1
      mutant, BADsubstitutionUL37x1 (BADsubUL37x1) induced cell death in hNPCs (m.o.i.
      = 1) to level which were indistinguishable from parental virus (BADwild-type)
      infected hNPCs. Surprisingly, although BADsubUL37x1 is growth defective in
      permissive HFFs, it produced infectious progeny in hNPCs with similar kinetics
      and to levels comparable to BADwild-type-infected hNPCs (m.o.i. = 1). While
      delayed at a lower multiplicity (m.o.i. = 0.3), the BADsubUL37x1 mutant reached
      similar levels to revertant within 12 days, in contrast to its phenotype in HFFs.
      The inability of pUL37x1/vMIA to protect hNPCs from HCMV-induced cell death did
      not result from impaired trafficking as pUL37x1/vMIA trafficked efficiently to
      mitochondria in transfected hNPCs and in HCMV-infected hNPCs. These results
      establish that pUL37x1/vMIA, although protective in permissive HFFs, does not
      protect HCMV-infected hNPCs from cell death under physiologically relevant oxygen
      tensions. They further suggest that pUL37x1/vMIA is not essential for HCMV growth
      in hNPCs and has different cell type-specific roles.

PMID- 22875258
TI  - Configurable 3D-Printed millifluidic and microfluidic 'lab on a chip'
      reactionware devices.
AB  - We utilise 3D design and 3D printing techniques to fabricate a number of
      miniaturised fluidic 'reactionware' devices for chemical syntheses in just a few
      hours, using inexpensive materials producing reliable and robust reactors. Both
      two and three inlet reactors could be assembled, as well as one-inlet devices
      with reactant 'silos' allowing the introduction of reactants during the
      fabrication process of the device. To demonstrate the utility and versatility of
      these devices organic (reductive amination and alkylation reactions), inorganic
      (large polyoxometalate synthesis) and materials (gold nanoparticle synthesis)
      processes were efficiently carried out in the printed devices.

PMID- 22875259
TI  - A voice-input voice-output communication aid for people with severe speech
      impairment.
AB  - A new form of augmentative and alternative communication (AAC) device for people
      with severe speech impairment-the voice-input voice-output communication aid
      (VIVOCA)-is described. The VIVOCA recognizes the disordered speech of the user
      and builds messages, which are converted into synthetic speech. System
      development was carried out employing user-centered design and development
      methods, which identified and refined key requirements for the device. A novel
      methodology for building small vocabulary, speaker-dependent automatic speech
      recognizers with reduced amounts of training data, was applied. Experiments
      showed that this method is successful in generating good recognition performance
      (mean accuracy 96%) on highly disordered speech, even when recognition perplexity
      is increased. The selected message-building technique traded off various factors
      including speed of message construction and range of available message outputs.
      The VIVOCA was evaluated in a field trial by individuals with moderate to severe
      dysarthria and confirmed that they can make use of the device to produce
      intelligible speech output from disordered speech input. The trial highlighted
      some issues which limit the performance and usability of the device when applied
      in real usage situations, with mean recognition accuracy of 67% in these
      circumstances. These limitations will be addressed in future work.

PMID- 22875260
TI  - Sensor-enabled RFID system for monitoring arm activity: reliability and validity.
AB  - After stroke, capacity to complete tasks in the treatment setting with the more
      affected arm is an unreliable index of actual use of that extremity in daily
      life. Available objective methods for monitoring real-world arm use rely on
      placing movement sensors on patients. These methods provide information on amount
      but not type of arm activity, e.g., functional versus nonfunctional movement.
      This paper presents an approach that places sensors on patients and household
      objects, overcoming this limitation. An accelerometer and the transmitter
      component of a radio-frequency proximity sensor are attached to objects; the
      receiver component is attached to the arm of interest. The receiver triggers an
      on-board radio-frequency identification tag to signal proximity when that arm is
      within 23 cm of an instrumented object. In benchmark testing, this system
      detected perfectly which arm was used to move the target object on 200 trials. In
      a laboratory study with 35 undergraduates, increasing the amount of time target
      objects were moved with the arm of interest resulted in a corresponding increase
      in system output   . Moreover, measurement error was low (   <= 2.5%). The
      results support this system's reliability and validity in individuals with
      unimpaired movement; testing is now warranted in stroke patients.

PMID- 22875261
TI  - Decoding dexterous finger movements in a neural prosthesis model approaching real
      world conditions.
AB  - Dexterous finger movements can be decoded from neuronal action potentials
      acquired from a nonhuman primate using a chronically implanted Utah Electrode
      Array. We have developed an algorithm that can, after training, detect and
      classify individual and combined finger movements without any a priori knowledge
      of the data, task, or behavior. The algorithm is based on changes in the firing
      rates of individual neurons that are tuned for one or more finger movement types.
      Nine different movement types, which consisted of individual flexions, individual
      extensions, and combined flexions of the thumb, index finger, and middle finger,
      were decoded. The algorithm performed reliably on data recorded continuously
      during movement tasks, including a no-movement state, with an overall average
      sensitivity and specificity that were both   > 92%. These results demonstrate a
      viable algorithm for decoding dexterous finger movements under conditions similar
      to those required for a real-world neural prosthetic application.

PMID- 22875262
TI  - Enhancing membrane protein subcellular localization prediction by parallel fusion
      of multi-view features.
AB  - Membrane proteins are encoded by ~ 30% in the genome and function importantly in
      the living organisms. Previous studies have revealed that membrane proteins'
      structures and functions show obvious cell organelle-specific properties. Hence,
      it is highly desired to predict membrane protein's subcellular location from the
      primary sequence considering the extreme difficulties of membrane protein wet-lab
      studies. Although many models have been developed for predicting protein
      subcellular locations, only a few are specific to membrane proteins. Existing
      prediction approaches were constructed based on statistical machine learning
      algorithms with serial combination of multi-view features, i.e., different
      feature vectors are simply serially combined to form a super feature vector.
      However, such simple combination of features will simultaneously increase the
      information redundancy that could, in turn, deteriorate the final prediction
      accuracy. That's why it was often found that prediction success rates in the
      serial super space were even lower than those in a single-view space. The purpose
      of this paper is investigation of a proper method for fusing multiple multi-view
      protein sequential features for subcellular location predictions. Instead of
      serial strategy, we propose a novel parallel framework for fusing multiple
      membrane protein multi-view attributes that will represent protein samples in
      complex spaces. We also proposed generalized principle component analysis (GPCA)
      for feature reduction purpose in the complex geometry. All the experimental
      results through different machine learning algorithms on benchmark membrane
      protein subcellular localization datasets demonstrate that the newly proposed
      parallel strategy outperforms the traditional serial approach. We also
      demonstrate the efficacy of the parallel strategy on a soluble protein
      subcellular localization dataset indicating the parallel technique is flexible to
      suite for other computational biology problems. The software and datasets are
      available at: http://www.csbio.sjtu.edu.cn/bioinf/mpsp.

PMID- 22875263
TI  - Extending myeloma survival:  targeting the seed and the soil.

PMID- 22875264
TI  - Helping the clinician help me: towards listening in cancer care.
AB  - Despite global support for the ideal of shared decision making, its enactment
      remains difficult in practice. The UK charity, Macmillan Cancer Support,
      attempted to incorporate the principles of shared decision making within a
      programme of distress management in Scotland. Distress management begins by
      completing the Distress Thermometer (DT). Although the DT is a screening tool,
      its function in this programme was extended to facilitate collaborative
      communication within a consultation. The aim of this grounded theory was to
      analyse the patient experience of the process. Nineteen people underwent semi
      structured interviews focused on their experience of distress management.
      Participants were a mixed-cancer cohort aged 40-79 years. Findings were discussed
      in a structured manner with a further 14 service users and carers, and 19
      clinical specialists in cancer. Constant comparison of all data revealed that the
      process of positive distress management could best be explained by reference to
      the core category: 'helping the clinician help me'. The emergence of this core
      category is detailed by situating its development within the iterative nature of
      the grounded theory method.

PMID- 22875265
TI  - Management of patients  with actinic keratoses.
AB  - Actinic keratoses (AKs) are precancerous skin lesions that develop on sun-exposed
      sites, such as the head, neck, hands and lower legs. Clinically, they present as
      red scaly patches and distribution can range from isolated lesions to extensive
      disease. This article considers the incidence and aetiology of AKs. The focus of
      discussion is on relevance to practice, outlining current treatment options and
      clarifying the support and guidance patients require in order to manage their
      condition effectively. Overall, the article aims to raise awareness of the
      condition so that health professionals caring for patients at risk of AK are
      better equipped to recognise the problem and identify when patients require
      treatment or referral to a specialist department.

PMID- 22875266
TI  - Momentum in cancer care: making the most of it.

PMID- 22875268
TI  - Technology: welcoming patient  information to the 21st century.

PMID- 22875267
TI  - Rehabilitation of patients following major head and neck cancer surgery.
AB  - Cancer rehabilitation is accepted as an essential part of patient care, aiming to
      maximise the patient's quality of life. Patients who have received major surgery
      for head and neck cancer face many challenges and require a tailored
      rehabilitation programme. This review collate the evidence specific to head and
      neck cancer patients and divides the programme into five areas: functional,
      medical, aesthetic, psychological and social. This provides an overall framework
      in which to consider these unique rehabilitation requirements.

PMID- 22875269
TI  - Implementing enhanced recovery  in gynaecology oncology.
AB  - Enhanced recovery involves the adoption of a selected number of evidence-based
      interventions used together and implemented in a 'fast track' care pathway during
      preoperative management, surgery itself and throughout the immediate
      postoperative period. Aimed at promoting effective patient recovery after
      surgery, this has been shown to improve the patient experience and facilitate
      early patient discharge following major surgery in some clinical areas
      (Department of Health, 2010). Applied to the clinical management and nursing care
      of women affected by gynaecological malignancies in one London tertiary referral
      centre hospital, enhanced recovery has been seen to improve patient experience
      and shorten the length of overall hospital stay. Implementation requires careful
      planning, appointment of key practitioners and commitment of the
      multidisciplinary team to realise successful outcomes. The authors' experience
      suggests that challenges are associated with changing practice and that while
      careful planning is essential, successes are to be gained, which significantly
      benefit patients, staff and the NHS Trust. In sharing this experience of
      implementing enhanced recovery, the authors hope to encourage others to consider
      application of this innovative strategy.

PMID- 22875272
TI  - Impact of a dithienyl unit on photostability of N,C-chelating boron compounds.
AB  - A dithienyl unit in a N,C-chelate monoboryl compound has been found to completely
      stabilize a N,C-chelate boryl chromophore toward photoisomerization. N,C-chelate
      diboryl compounds that contain a dithienyl unit display a similar high stability
      toward photoisomerization. This greatly enhanced photostability is attributed to
      the pi    ->    pi* transition and luminescence involving the dithienyl unit that
      competes effectively with photoisomerization of the boryl chromophore.

PMID- 22875273
TI  - A guide to entering  NHS management.

PMID- 22875274
TI  - Managing heparin infusions.

PMID- 22875275
TI  - Assessment of the patient with neutropenic sepsis.

PMID- 22875276
TI  - Life after allogeneic bone marrow transplant.

PMID- 22875277
TI  - alpha-Ketoglutarate-related inhibitors of HIF prolyl hydroxylases are substrates
      of renal organic anion transporters 1 (OAT1) and 4 (OAT4).
AB  - 2-Oxoglutarate or alpha-ketoglutarate (alphaKG) is a substrate of HIF prolyl
      hydroxylases 1-3 that decrease cellular levels of the hypoxia-inducible factor
      1alpha (HIF-1alpha) in the presence of oxygen. alphaKG analogs are applied to
      stabilize HIF-1alpha even in the presence of oxygen and thus provide a novel
      therapeutic option in treating kidney diseases. In the kidneys, the organic anion
      transporters 1 and 3 (OAT1 and OAT3, respectively) in cooperation with the sodium
      dependent dicarboxylate transporter 3 (NaDC3) and the OAT4 might be responsible
      for the uptake of alphaKG analogs into and the efflux out of the tubular cells.
      Using the radiolabelled substrates p-aminohippurate (PAH, OAT1), estrone-3
      sulfate (ES; OAT3, OAT4), and succinate (NaDC3), N-oxalylglycine (NOG),
      dimethyloxalyl glycine (DMOG), 2,4-diethylpyridine dicarboxylate (2,4-DPD), and
      pyridine-2,4-dicarboxylic acid (PDCA) were tested in cis-inhibition and trans
      stimulation experiments. None of these alphaKG analogs interacted with NaDC3. 2,4
      DPD and PDCA inhibited ES uptake by OAT3 moderately. NOG, 2,4-DPD and PDCA, but
      not DMOG, inhibited PAH uptake by OAT1 significantly. trans-Stimulation
      experiments and experiments demonstrating stabilization of HIF-1alpha revealed
      that NOG and PDCA, but not 2,4-DPD, are translocated by OAT1. All compounds trans
      stimulated ES uptake by OAT4, but only PDCA stabilized HIF-1alpha. The data
      suggest that OAT1 is involved in the uptake of NOG and PDCA across the
      basolateral membrane of proximal tubule cells, whereas OAT4 may release these
      compounds into the primary urine.

PMID- 22875278
TI  - The role of chemosensitive afferent nerves and TRP ion channels in the
      pathomechanism of headaches.
AB  - The involvement of trigeminovascular afferent nerves in the pathomechanism of
      primary headaches is well established, but a pivotal role of a particular class
      of primary sensory neurons has not been advocated. This review focuses on the
      evidence that supports the critical involvement of transient receptor potential
      (TRP) channels in the pathophysiology of primary headaches, in particular,
      migraine. Transient receptor potential vanilloid 1 and transient receptor
      potential ankyrin 1 receptors sensitive to vanilloids and other irritants are
      localized on chemosensitive afferent nerves, and they are involved in meningeal
      nociceptive and vascular responses involving neurogenic dural vasodilatation and
      plasma extravasation. The concept of the trigeminal nocisensor complex is put
      forward which involves the trigeminal chemosensitive afferent fibers/neurons
      equipped with specific nocisensor molecules, the elements of the meningeal
      microcirculatory system, and the dural mast cells. It is suggested that the
      activation level of this complex may explain some of the specific features of
      migraine headache. Pharmacological modulation of TRP channel function may offer a
      novel approach to the management of head pain, in particular, migraine.

PMID- 22875279
TI  - Occult hepatitis B infection in the immigrant population of Sicily, Italy.
AB  - In Italy, about 7 % of the resident population is represented by immigrants
      originating from geographic regions at high endemicity for hepatitis B virus
      infection. This study aims to assess the prevalence of occult HBV infection (OBI)
      including the identification of HBV-genotypes in a population of immigrants
      serologically negative for hepatitis B surface antigen (HBsAg). Between May 2006
      and May 2010, 339 immigrants were tested for markers of HBV, hepatitis C virus
      (HCV) and human immunodeficiency virus (HIV) infections. HBV-DNA was tested by
      using nested-PCR assays on three different genetic region. HBV-DNA was detected
      in plasma samples of 11/339 (3.2 %) patients. Most of them had no serological
      markers of HBV infection, 3/58 (5.2 %) were anti-HBc-alone, and 4/13 (30.8 %)
      were anti-HIV positive. HIV positivity was the only factor independently
      associated with the higher probability of observing OBI (OR = 16.5, p < 0.001).
      No HCV co-infected patients were found. Genotype D was detected in 9/11 (81.8 %)
      OBI cases, while the remaining two (18.2 %) were classified as genotype E.
      Although OBI was found at lower rate than expected among immigrants from highly
      endemic countries, anti-HBc alone positivity was confirmed as a sentinel marker
      of occult HBV infection. Nevertheless, a marked heterogeneity of HBV markers was
      found among HBV-DNA positive subjects. Our finding evidenced the predominance of
      HBV-genotype D viral strains among OBI cases, also in those from geographical
      areas where overt HBV infections are mainly sustained by viral genotypes other
      than D. 

PMID- 22875280
TI  - Leveraging family values to decrease unhealthy alcohol use in aging Latino day
      laborers.
AB  - In one Los Angeles study, 20 % of day laborers reported excessive drinking. Older
      adults are more sensitive to alcohol's effects, yet heavy drinking persists among
      Latinos until they are in their 60s. No interventions to reduce heavy drinking
      exist for aging day laborers. We recruited 14 day laborers aged 50 and older in
      Los Angeles. We identified their unhealthy alcohol use behaviors and
      comorbidities and conducted semi-structured interviews to understand their
      perceptions of unhealthy alcohol use. We found social disadvantages and
      conditions exacerbated by alcohol use, like depression. Participants were
      concerned with dying and premature aging, and reported that family could
      influence behavior change. An intervention should consider (1) integrating family
      values and (2) increasing knowledge about alcohol use and comorbidities. Further
      studies are needed to explore family influence on aging Latino day laborers.

PMID- 22875281
TI  - VAS2870 is a pan-NADPH oxidase inhibitor.

PMID- 22875282
TI  - Lectin microarrays differentiate carcinoma cells from reactive mesothelial cells
      in pleural effusions.
AB  - The aim of this study was to evaluate the diagnostic utility of lectin
      microarrays in pleural effusions of patients with lung cancer. A lectin
      microarray, LTL, PSA, LCA, UEA-1, AAL, MAL-I, MAL-II, SNA, WGA, ECL, DSA, STL,
      SWGA, HPA, ConA, GNA, HHL, BPL, EEL, Jacalin, WFA, ACL, MPL, DBA, SBA, was used
      to determine the glycoprotein profile of cells in pleural effusions from patients
      with lung cancer (54 cases), and with benign lung disease (54 cases). The A549
      cell line, used as an experimental control, was positive for AAL, MAL-I, WGA,
      STL, Jacalin and ACL binding. Adenocarcinoma cells in pleural effusions were
      positive for ECL, DSA, AAL, MAL-I, WGA, STL, Jacalin, and ACL binding. AAL, WGA,
      and ACL positive binding was the most common, found in 54, 48, and 38 samples,
      respectively. ECL and DSA binding was positive in only 4 samples. In comparison,
      reactive mesothelial cells displayed positive binding for all markers in the
      microarray panel. SNA and AAL positive binding was detected in the majority of
      samples; 50/54 and 48/54 samples, respectively. Positive binding of DBA, MAL-II
      and EEL was present in only 2, 4 and 4 samples, respectively. SNA binding had the
      highest sensitivity (92.6 %), specificity (100 %), and accuracy (96.3 %). SNA may
      be used as a biomarker to distinguish reactive mesothelial cells from
      adenocarcinoma cells. The lectin microarrays proved able to distinguish carcinoma
      cells from reactive mesothelial cells in pleural effusions.

PMID- 22875283
TI  - Effect of titanium dioxide nanoparticles on gamma-ray treatment of phenol in
      different matrices: implications in toxicity toward Daphnia magna.
AB  - Gamma-ray treatment of phenol was studied in terms of both chemical degradation
      and toxicological change. About 90% of phenol (5.0 * 10(-4) M) in ultrapure water
      (UW) was eliminated by gamma-irradiation at a dose of 10 kGy, but acute toxicity
      was dramatically increased, particularly for dose of 1 kGy, due to the formation
      of more toxic by-products such as hydroquinone, benzoquinone, resorcinol and
      catechol. The addition of TiO(2) nanoparticles had little effect on the removal
      of phenol in UW, but substantially enhanced the mineralization of phenol compared
      with gamma-irradiation alone. Additionally, degradation of phenol by gamma
      irradiation was inhibited in a wastewater effluent (WE) matrix, likely due to the
      presence of dissolved organic carbon (22.06 mg L(-1)). Furthermore, lower
      concentrations of toxic by-products were generated both in WE and in the presence
      of TiO(2) nanoparticles, resulting in reduction of toxicity increase by gamma
      irradiation. Meanwhile, the toxicity of gamma-ray treated phenol in WE was well
      estimated with simple summation of individual toxicity of phenol and by-products
      (R (2) = 0.9678).

PMID- 22875284
TI  - Stress-response protein expression and DAF-16 translocation were induced in
      tributyltin-exposed Caenorhabditis elegans.
AB  - Exposure to tributyltin (TBT) with graded sublethal doses (0, 1, 10, 50 and 200
      nM) resulted in the release of reactive oxygen species (ROS) and DNA damage in
      the nematode Caenorhabditis elegans. After the worms carrying transgenic
      reporters were exposed to TBT, the expressions of superoxide dismutase (SOD-3),
      glutathione S-transferase (GST-4) and heat shock proteins (HSP-4, HSP-16.2 and
      HSP-70) were semi-quantified after exposure. The results indicated that TBT
      caused dose-dependent induction of SOD-3, GST-4, HSP-4 and HSP-70. Furthermore,
      TBT exposure also induced DAF-16 translocation from cytoplasm to nucleus. The
      results implicated that C. elegans might be a potential animal model for TBT
      level monitoring and toxicity assessment.

PMID- 22875285
TI  - Investigation of fluoroquinolones, sulfonamides and macrolides in long-term
      wastewater irrigation soil in Tianjin, China.
AB  - Fluoroquinolones, sulfonamides and macrolides were analyzed in soil samples
      collected from suburban areas in Tianjin, China. Fluoroquinolones were the
      predominant class of antibiotics. The mean total concentration of
      fluoroquinolones (33.56 MUg/kg) was 30-fold higher than one of macrolides, which
      were the second dominant class antibiotics. Sulfonamides showed the lowest level
      in soil. The spatial distribution of fluoroquinolones showed wastewater
      irrigation was a potential source of antibiotics. The individual antibiotics
      levels were all below the trigger value (100 MUg/kg) set by the Steering
      Committee of Veterinary International Committee, indicating the low risk for
      organisms in the agricultural soils of Tianjin.

PMID- 22875286
TI  - Residues of organochlorine pesticides in water and suspended particulate matter
      from Xiangshan Bay, East China Sea.
AB  - Residual levels, distribution and possible sources of organochlorine pesticides
      (OCPs) in nine water column and suspended particulate matter (SPM) samples
      collected from Xiangshan Bay, East China Sea were investigated. Total OCPs
      concentrations in water column and SPM ranges from 2.88 to 34.72 ng/L and 2.47 to
      29.94 ng/L, respectively, which exceed the US Environmental Protection Agency
      regulatory limits. Moreover, low ratio of alpha-HCH/gamma-HCH and high ratios
      beta- and gamma-HCH suggested the cocktail input pattern of fresh and weathered
      HCHs. Meanwhile, low ratio of (DDE + DDD)/DDT and high ratios p,p'- and o,p'-DDT
      reflected a "dicofol type DDT pollution" pattern.

PMID- 22875287
TI  - Regenerable hydrogen storage in lithium amidoborane.
AB  - Regenerable hydrogen storage of lithium amidoborane is firstly achieved through
      the routes of direct thermal dehydrogenation and subsequent chemical
      hydrogenation of its dehydrogenated products by treatment with hydrazine in
      liquid ammonia.

PMID- 22875288
TI  - Cocaine-induced vasculitis: clinical and immunological spectrum.
AB  - Levamisole-contaminated cocaine has recently been recognized in North America and
      Europe, and its use is associated with a variety of clinical and autoimmune
      abnormalities. The clinical characteristic seems to be the presence of a painful
      purpuric skin rash that predominantly affects the ear lobes and cheeks, often
      accompanied by systemic manifestations including fever, malaise, arthralgias,
      myalgias, and laboratory abnormalities, for example leukopenia, neutropenia,
      positive ANA, ANCA, and phospholipid antibodies. Most of these manifestations can
      be seen with the use of either drug, especially levamisole. There is no specific
      therapy, and discontinuation of its use is followed by improvement. Prednisone
      and immunosuppressive therapy may be needed at times. Further use of the drug is
      characterized by recurrence of most of the complaints.

PMID- 22875289
TI  - A retrospective analysis of germline competence in rat embryonic stem cell lines.
AB  - The factors responsible for conferring germline competence in embryonic stem (ES)
      cell lines remain unidentified. In the present study, rat ES cell lines (n = 17)
      were established with 3i medium (SU5402, PD0325901, CHIR99021), 2i medium
      (PD0325901, CHIR99021) or 2iF medium (PD0325901, CHIR99021, forskolin), and their
      potential for germline transmission to the G1 generation was examined. Rat
      strains were divided into an albino group (F344, Wistar or CAG/Venus transgenic
      rats with the Wistar background) or a colored coat group (Brown-Norway, Dark
      Agouti, or BLK rats selected from >F3 generations of Wistar * Dark-Agouti rats
      based on their black coat color). Successful germline transmission was observed
      in 57 % (4/7), 40 % (2/5) and 100 % (5/5) of the ES cells established with 3i, 2i
      and 2iF media, respectively. ES cell lines from the homozygous CAG/Venus
      transgenic rats were established in all three media, but only the lines
      established with the 2iF medium were germline-competent. Neither coat-color
      (albino: 64 %, 7/11; colored: 67 %, 4/6) nor gender of the ES cell lines (XX: 67
      %, 2/3; XY: 64 %, 9/14) were likely to affect germline transmission.

PMID- 22875290
TI  - RWRMDA: predicting novel human microRNA-disease associations.
AB  - Recently, more and more research has shown that microRNAs (miRNAs) play critical
      roles in the development and progression of various diseases, but it is not easy
      to predict potential human miRNA-disease associations from the vast amount of
      biological data. Computational methods for predicting potential disease-miRNA
      associations have gained a lot of attention based on their feasibility, guidance
      and effectiveness. Differing from traditional local network similarity measures,
      we adopted global network similarity measures and developed Random Walk with
      Restart for MiRNA-Disease Association (RWRMDA) to infer potential miRNA-disease
      interactions by implementing random walk on the miRNA-miRNA functional similarity
      network. We tested RWRMDA on 1616 known miRNA-disease associations based on leave
      one-out cross-validation, and achieved an area under the ROC curve of 86.17%,
      which significantly improves previous methods. The method was also applied to
      three cancers for accuracy evaluation. As a result, 98% (Breast cancer), 74%
      (Colon cancer), and 88% (Lung cancer) of top 50 predicted miRNAs are confirmed by
      published experiments. These results suggest that RWRMDA will represent an
      important bioinformatics resource in biomedical research of both miRNAs and
      diseases.

PMID- 22875291
TI  - What makes a good nurse?

PMID- 22875292
TI  - Advances in stoma care  and specialist nursing.

PMID- 22875293
TI  - Blood glucose monitoring:  an overview.
AB  - Glucose monitoring is done to obtain information on blood glucose levels to
      ensure a therapeutic regimen; the aim is to maintain consistent glucose levels
      and avoid hypoglycaemia and hyperglycaemia. Self-management is central to
      diabetes control. Diabetes is individual, so self-monitoring of blood glucose
      (SMBG) targets and frequency of testing must be decided to meet each patient's
      needs. Nurses have key roles in education and advocacy. They can educate patients
      on what affects glucose levels, why they need to carry out SMBG, and how to
      interpret and act on the results. Nurses also match glucose monitoring meters to
      patients' needs by considering ease of use, technical features and lifestyle.
      Access to testing supplies is sometimes restricted through blanket policies and
      nurses have an advocacy role here in challenging inappropriate restrictions.

PMID- 22875294
TI  - In pursuit of excellence in diabetes care: trends in insulin delivery.
AB  - Diabetes mellitus has been estimated to affect 2.9 million people in the UK.
      Large-scale clinical trials conclusively demonstrate that elevated blood glucose
      levels are associated with an increased risk of micro- and macrovascular
      complications. The high rates of morbidity and mortality associated with this
      condition demonstrate how important effective glycaemic control is. Subcutaneous
      insulin injection continues to be the mainstay of therapy for all people with
      type 1 diabetes mellitus and the majority of individuals with type 2 diabetes
      mellitus. However, there are a number of barriers to insulin therapy. For
      example, conventional insulin delivery is arguably time consuming. Furthermore,
      it has been associated with common errors, such as inaccurate dosing and
      administration (National Patient Safety Agency, 2010). Insulin pen devices have
      various advantages over conventional delivery. Their ease of use and
      incorporation into busy lifestyles may improve diabetes control with much less
      effort, while maintaining adherence and quality of life. Research in insulin
      delivery shows there is a prospect of needle-free delivery in the near future.
      Despite such progress, the role of the healthcare professionals in involving,
      assessing, supporting and educating people having insulin therapy, including the
      attainment of the agreed blood glucose levels, cannot be overestimated.

PMID- 22875295
TI  - iCare advanced blood  glucose monitoring system.
AB  - Health professionals working in the field of diabetes have a wide choice of blood
      glucose meters to offer patients, with different meters offering different
      options for monitoring and recording blood glucose results. Self-monitoring of
      blood glucose levels can be helpful to people with diabetes in helping to
      maintain day-to-day control, adjusting insulin doses, detecting hypoglycaemia,
      assessing control during intercurrent illness and helping to provide information
      that can be used in the prevention of long-term complications. The newly released
      iCare Advanced Blood Glucose monitoring System is an easy-to-teach and use blood
      glucose meter using the latest technology to provide people with diabetes with
      easy and comfortable testing, producing accurate blood glucose test results in
      just 6 seconds using a small blood sample of only 0.7ul. In the current NHS
      climate, the iCare Advanced blood Glucose meter offers patients and health
      professionals the latest technology alongside cost savings by providing a test
      strip that is low cost but does not compromise on quality.

PMID- 22875296
TI  - PROMs: a novel approach  to arthritis self-management.
AB  - Despite our knowledge of many effective education techniques, there is little
      evidence that clinicians have incorporated them into their daily practices. One
      of the reasons for the underutilization of patient education may be that
      physicians are expecting the specialist nurses to provide this service, whereas
      the nurses lack any formal protocol for patient education in standard clinical
      practice. Self-management programmes are now acknowledged as a key element of
      quality care. A high priority for research is the development and diffusion of
      patient education strategies that are tailored to address patient needs and
      applicable for the standard day to day practice. This paper describes the
      rationale and design of the 'Joint Fitness Program' which is a new patient-based
      educational programme integrating patient-reported outcome measures (PROMs) and
      self-management for people with inflammatory arthritis. This education programme,
      which illustrates how theory can explicitly be translated into practice,
      addresses PROMs as an objective tool to assess the educational needs of patients
      with arthritis and uses the PROMs to design an education programme and not just
      evaluate the disease activity.

PMID- 22875297
TI  - Regulation of cosmetic nursing:  the BACN's standpoint.

PMID- 22875299
TI  - Preceptorship: an essential component of qualification.

PMID- 22875298
TI  - Physical activity and learning disability.
AB  - The inclusion of people with learning disabilities in sporting activities
      promotes a number of positive outcomes. These may include opportunities for
      social inclusion, the creation of positive role models for other people with
      learning disabilities, the opportunity to present people with learning
      disabilities in valued social roles to a global community, sharing of common
      interests and experiences, and social and competitive rewards. There is also the
      potential for positive physical and mental health outcomes. Current data suggests
      that people with learning disabilities are physically less active than the rest
      of the population, more likely to lead sedentary lifestyles and more prone to
      obesity and associated health conditions. However, there are a number of ways in
      which nurses may support both individuals and their carers to engage with and
      promote programmes of physical activity. These may include the design of
      individual activity plans incorporated within health action planning aligned with
      suitable rewards systems. Action might also be taken in terms of health promotion
      advice and information to carers and those providing facilities for physical
      activity.

PMID- 22875300
TI  - Enhancing the role of the school  nurse in contemporary society.

PMID- 22875301
TI  - The scale of errors in prescribing medication in general practice.

PMID- 22875302
TI  - Professional development: from staff nurse to nurse consultant. Part 12: series
      summary.

PMID- 22875303
TI  - Critical care: the eight vital  signs of patient monitoring.
AB  - Nurses have traditionally relied on five vital signs to assess their patients:
      temperature, pulse, blood pressure, respiratory rate and oxygen saturation.
      However, as patients hospitalised today are sicker than in the past, these vital
      signs may not be adequate to identify those who are clinically deteriorating.
      This paper describes clinical issues to consider when measuring vital signs as
      well as proposing additional assessments of pain, level of consciousness and
      urine output, as part of routine patient assessment.

PMID- 22875304
TI  - International Nurses Day: did you pause and reflect?

PMID- 22875305
TI  - Sleep and violence.
AB  - OPINION STATEMENT: Treatment of violent behaviors in sleep depends on the
      underlying condition and a correct identification of the causative disorder is
      mandatory. After eliminating possible precipitating factors, pharmacological
      treatment is often required to control violent sleep behaviors. Although no drugs
      are specifically approved for the treatment of parasomnias and placebo-controlled
      trials are lacking in these patient populations, clonazepam is considered the
      drug of choice in the management of both Non-REM and REM parasomnias.
      Benzodiazepines may cause unwanted side effects especially in older individuals
      and tolerance is sometime observed. Melatonin and pramipexole may represent
      alternative options in REM sleep behavior disorder. Hypnosis therapy may be
      considered in arousal disorders when pharmacological treatment is contraindicated
      or ineffective. Management of nocturnal frontal lobe epilepsy include a first
      step pharmacological approach with antiepileptic drugs (eg, carbamazepine,
      oxcarbazepine or other drugs effective on partial seizures), but surgical options
      may be considered in drug refractory patients. The published evidence for the
      efficacy of various treatments relies mostly upon case series or case reports.

PMID- 22875306
TI  - Vascular diseases of the spinal cord: a review.
AB  - OPINION STATEMENT: * In acute spinal cord ischemia syndrome (ASCIS), treatment
      recommendations are derived from data of cerebral ischemic stroke,
      atherosclerotic vascular disease and acute spinal cord injury. Besides acute
      management, secondary prevention is of major importance. Pathologies affecting
      the aorta as well as underlying cerebrovascular conditions should be treated
      whenever possible.* ASCIS may occur after aortic surgery, less often after
      thoracic endovascular aortic repair (TEVAR). Protocols are proposed.* Acute
      spinal cord hemorrhage can be treated surgically and/or pharmacologically.*
      Symptomatic treatment in patients with a spinal cord lesion is of major
      importance. Depending on level and extension of the lesion, there is a risk for
      systemic and neurological complications, which may be life-threatening.* Each
      spinal vascular malformation is a unique lesion that needs an individualized
      treatment algorithm. In case of a symptomatic vascular malformation, endovascular
      intervention is the primary treatment option.* Spinal dural Arteriovenous fistula
      (AVF) may be treated endovascularly or surgically. If preoperative localization
      of the fistula is possible, surgery is feasible with a low complication rate. In
      comparison, endovascular approaches are less invasive.* Spinal AVM are rather
      treated endovascularly than surgically or in a stepwise multidisciplinary
      approach.* Symptomatic and exophytic spinal cavernous angiomas should be treated
      surgically. Deep spinal cavernous angiomas that are asymptomatic or only show
      mild symptoms can be observed.

PMID- 22875307
TI  - Increase of epidermal growth factor receptor expression in progression of GERD,
      Barrett, and adenocarcinoma of esophagus.
AB  - INTRODUCTION: Gastroesophageal reflux disease (GERD) is a pathology with a wide
      range of clinical and endoscopic manifestations. Epidermal growth factor receptor
      (EGFR), found in the epithelium of the digestive tract, plays an important role
      in epithelial repair and shows increased expression in different neoplasms,
      including esophageal tumors. OBJECTIVES: The purpose of this study was to
      evaluate EGFR expression using immunohistochemistry in esophageal biopsies
      obtained from patients with GERD, Barrett's esophagus, and adenocarcinoma of the
      esophagus. METHODS: EGFR expression was immunohistochemically determined in
      biopsies from 194 patients with symptoms suggestive of GERD or adenocarcinoma of
      the esophagus, seen at two Brazilian university hospitals between January 2003
      and December 2008. Based on histopathological analysis, patients were divided
      into three groups: GERD, Barrett's esophagus and adenocarcinoma of the esophagus.
      EGFR expression was considered positive when staining was detected in the
      membrane. RESULTS: Mean age was 55.25 years (range 30-90). Patients with GERD (n
      = 127) accounted for 65.5% of the sample, compared with 12.4% (n = 24) of
      patients with Barrett's esophagus and 22.2% (n = 43) of patients with esophageal
      adenocarcinoma. Immunohistochemical analysis was positive for EGFR in 19.1% of
      the patients (37/194), divided as follows: 8.7% (11/127) in the GERD group, 25%
      (6/24) in the Barrett's esophagus group, and 46.5% (20/43) in the esophageal
      adenocarcinoma group. Statistical analysis revealed significant differences
      between the three groups (p = 0.0001). CONCLUSIONS: GERD patients showed lower
      levels of EGFR expression than patients with Barrett's esophagus or patients with
      adenocarcinoma of the esophagus, suggesting a direct relationship between EGFR
      expression and disease progression.

PMID- 22875308
TI  - Hepatic arteriovenous fistulae: role of interventional radiology.
AB  - INTRODUCTION: Hepatic arterial venous fistulae are abnormal communications
      between the hepatic artery and portal or hepatic vein and commonly occur either
      secondary to iatrogenic causes like liver biopsy, transhepatic biliary drainage,
      transhepatic cholangiogram and surgery, or following mechanical insult like blunt
      or penetrating trauma. Congenital fistulae are rare. Treatment is warranted as an
      emergency management or in the development of portal hypertension/heart failure
      in chronic cases. Both surgical and endovascular occlusion of the fistula can be
      attempted with the latter carrying low intra and post-procedure morbidity.
      Endovascular treatment has thus currently emerged as a minimally invasive
      reliable treatment option in such individuals. METHODS AND RESULTS: We describe a
      short series consisting of four cases of acquired hepatic arterioportal/venous
      fistulae, which were referred to interventional radiology for endovascular
      management over the last 2 years. Three patients had arterio-portal communication
      and one patient had communication between the hepatic artery and middle hepatic
      vein. Successful embolization through the transarterial route was achieved in all
      four patients. A brief discussion of these cases is presented along with a
      relevant review of literature. CONCLUSIONS: Endovascular techniques currently
      form less invasive and first line treatment options in arterioportal/venous
      fistulae, surgery being reserved only for unsuccessful embolizations/complex
      fistulae.

PMID- 22875309
TI  - Improved detection of incident dysplasia by probe-based confocal laser
      endomicroscopy in a Barrett's esophagus surveillance program.
AB  - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is a new technique
      allowing in vivo detection of neoplastic tissue using a standard endoscope. AIMS:
      Our aim was to compare the incident dysplasia detection rate of biopsies obtained
      by high-definition white light endoscopy (HD-WLE) or by pCLE in a cohort of
      patients with Barrett's esophagus (BE) participating in a surveillance program.
      METHODS: Fifty of 100 patients underwent pCLE in addition to HD-WLE. Four
      quadrant biopsy specimens according to the Seattle biopsy protocol were obtained
      in all patients to ensure standard-of-care. Diagnosis of dysplasia/neoplasia was
      made by a blinded gastrointestinal pathologist. RESULTS: Incident high-grade
      dysplasia (HGD) and low-grade dysplasia (LGD) were diagnosed in 3/100 and in
      16/100 cases. In the HD-WLE group, areas suspicious for neoplasia were not
      observed and dysplasia was diagnosed in 5/50 (10%) patients (one with HGD). In
      the pCLE group, areas suspicious for neoplasia were observed by pCLE in 21/50
      (42%) patients; dysplasia was confirmed in 14 cases (28%) (two with HGD). The
      dysplasia detection rate was significantly higher in the pCLE group than in the
      HD-WLE group (P = 0.04). The sensitivity, specificity, positive and negative
      predictive values of pCLE for dysplasia were 100, 83, 67, and 100%, respectively.
      CONCLUSIONS: Incident dysplasia can be more frequently detected by pCLE than by
      HD-WLE in BE. The higher dysplasia detection rate provided by pCLE could improve
      the efficacy of BE surveillance programs.

PMID- 22875310
TI  - Interpretation of probe-based confocal laser endomicroscopy of indeterminate
      biliary strictures: is there any interobserver agreement?
AB  - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) has enabled in vivo
      histopathology by obtaining high resolution images of the mucosal layers of the
      gastrointestinal tract. For indeterminate bile duct strictures, biopsy, cytologic
      brushing and needle aspiration have low levels of diagnostic accuracy. AIM: The
      objective of this multi-center pilot study was to assess the interobserver
      agreement in interpretation of pCLE imaging. METHODS: Twenty-five de-identified
      pCLE video clips of indeterminate biliary strictures were sent to 6 observers at
      5 institutions. Miami Classification was used to standardize image
      interpretation. Seven variables were assessed for interobserver agreement using
      the Fleiss kappa statistic which included: presence of thick (>20 MUm) or thin
      (<20 MUm) dark or white bands, dark clumps, epithelium including glandular
      structures, interstitial fluorescein leakage, ease of interpretation, and final
      diagnosis. Based on operator experience, observers were categorized into 3
      categories of experience (Category 1: 0-10; Category 2: 11-20; Category 3: >21
      cases). RESULTS: Upon stratification, Category 1 interobserver agreement ranged
      from "Poor" to "Fair" (kappa = 0.277, kappa = -0.079, kappa = -0.025, kappa = 
      0.066, kappa = 0.128, kappa = 0.088), and for the final diagnosis variable, the
      agreement was slight (kappa = 0.033). Category 2 and 3 interobserver agreement
      ranged from "Poor" to "Fair" (kappa = 0.211, kappa = 0.181, kappa = 0.347, kappa
      = 0.238, kappa = -0.050, kappa = 0.092), and for the final diagnosis variable,
      the agreement was slight (kappa = 0.195). CONCLUSION: The overall interobserver
      agreement for pCLE image interpretation in indeterminate biliary strictures
      ranges from poor to fair. Interpretation criteria as well as training require
      further standardization toward improving inter-rater reliability.

PMID- 22875311
TI  - Advancing the next generation of health risk assessment.
AB  - BACKGROUND: Over the past 20 years, knowledge of the genome and its function has
      increased dramatically, but risk assessment methodologies using such knowledge
      have not advanced accordingly. OBJECTIVE: This commentary describes a
      collaborative effort among several federal and state agencies to advance the next
      generation of risk assessment. The objective of the NexGen program is to begin to
      incorporate recent progress in molecular and systems biology into risk assessment
      practice. The ultimate success of this program will be based on the incorporation
      of new practices that facilitate faster, cheaper, and/or more accurate
      assessments of public health risks. METHODS: We are developing prototype risk
      assessments that compare the results of traditional, data-rich risk assessments
      with insights gained from new types of molecular and systems biology data. In
      this manner, new approaches can be validated, traditional approaches improved,
      and the value of different types of new scientific information better understood.
      DISCUSSION AND CONCLUSIONS: We anticipate that these new approaches will have a
      variety of applications, such as assessment of new and existing chemicals in
      commerce and the design of chemical products and processes that reduce or
      eliminate the use or generation of hazardous substances. Additionally, results of
      the effort are likely to spur further research and test methods development. Full
      implementation of new approaches is likely to take 10-20 years.

PMID- 22875312
TI  - A rare case report of simultaneous presentation of myopathy, Addison's disease,
      primary hypoparathyroidism, and Fanconi syndrome in a child diagnosed with Kearns
      Sayre syndrome.
AB  - Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined
      as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age
      20 years, and one of the following: cardiac conduction defects, cerebellar
      syndrome, or cerebrospinal fluid protein above 100 mg/dl. KSS may affect many
      organ systems causing endocrinopathies, encephalomyopathy, sensorineural hearing
      loss, and renal tubulopathy. Clinical presentation at diagnosis is quite
      heterogeneous and, usually, few organs are affected with progression to
      generalized disease early in adulthood. We present the case of a boy with KSS
      presenting at the age of 5 years with myopathy, Addison's disease, primary
      hypoparathyroidism, and Fanconi syndrome. The proper replacement treatment along
      with the administration of mitochondrial metabolism-improving agents had a brief
      ameliorating effect, but gradual severe multisystemic deterioration was
      inevitable over the next 5 years. CONCLUSION: This report highlights the fact
      that in case of simultaneous presentation of polyendocrinopathies and renal
      disease early in childhood, KSS should be considered.

PMID- 22875313
TI  - Influence of obesity on nocturnal oxygen saturation in young children.
AB  - Obesity is increasing worldwide and it is accompanied by major health effects. In
      adults and school-aged children, obesity is associated with decreased respiratory
      function, which may lead to disturbed sleeping and subsequently difficulties in
      concentration and behavioural disorders. The evidence for the association between
      obesity and decreased respiratory function in younger children is scarce. To
      explore the association between body weight and nocturnal respiratory function in
      young children, 1 to 3 years old, nocturnal pulse oximetry was performed at home.
      Children with tonsillar hypertrophy were excluded. Percentage of time with oxygen
      saturation (SpO(2)) <95 % was measured and its association with body mass index
      (BMI) for age z scores was analysed. Pulse oximetric data of 51 children,
      including 18 children with a BMI for age above +2 standard deviations, were
      obtained for this study. Linear regression analysis, correction for gender and
      parental smoking, showed a positive association between the natural logarithm of
      SpO(2) <95 % and BMI for age z score [regression coefficient (beta) 0.19, 95 %
      confidence interval 0.00-0.39]. CONCLUSION: In young children, higher body weight
      is associated with a decrease in nocturnal oxygen saturation.

PMID- 22875314
TI  - Care delivery and outcomes among Belgian children and adolescents with type 1
      diabetes.
AB  - We aimed to investigate care processes and outcomes among children and
      adolescents with type 1 diabetes treated in hospital-based multidisciplinary
      paediatric diabetes centres. Our retrospective cross-sectional study among 12
      Belgian centres included data from 974 patients with type 1 diabetes, aged 0-18
      years. Questionnaires were used to collect data on demographic and clinical
      characteristics, as well as process of care completion and outcomes of care in
      2008. Most patients lived with both biological or adoption parents (77 %) and had
      at least one parent of Belgian origin (78 %). Nearly all patients (>=95 %)
      underwent determination of HbA(1c) and BMI. Screening for retinopathy (55 %) and
      microalbuminuria (73 %) was less frequent, but rates increased with age and
      diabetes duration. Median HbA(1c) was 61 mmol/mol (7.7 %) [interquartile range 54
      68 mmol/mol (7.1-8.4 %)] and increased with age and insulin dose. HbA(1c) was
      higher among patients on insulin pump therapy. Median HbA(1c) significantly
      differed between centres [from 56 mmol/mol (7.3 %) to 66 mmol/mol (8.2 %)].
      Incidence of severe hypoglycaemia was 30 per 100 patient-years. Admissions for
      ketoacidosis had a rate of 3.2 per 100 patient-years. Patients not living with
      both biological or adoption parents had higher HbA(1c) and more admissions for
      ketoacidosis. Parents' country of origin was not associated with processes and
      outcomes of care. CONCLUSION: Outcomes of care ranked well compared to other
      European countries, while complication screening rates were intermediate. The
      observed centre variation in HbA(1c) remained unexplained. Outcomes were
      associated with family structure, highlighting the continuing need for strategies
      to cope with this emerging challenge.

PMID- 22875315
TI  - Popliteal artery entrapment presenting as acute limb ischemia: treatment with
      intra-arterial thrombolysis. Case report and review of the literature.
AB  - Popliteal artery entrapment syndrome (PAES) is a relatively rare condition, which
      occurs predominantly in active young adults who lack atherogenic risk factors. It
      has been rarely reported in patients under the age of 18 years. The most common
      presentation in the early stages is intermittent claudication; however, in the
      later stages of undiagnosed PAES, acute ischemia can occur as a result of
      complete arterial occlusion or embolism. We present a 14-year-old boy, who
      presented with acute limb ischemia which was managed with a multidisciplinary
      approach.

PMID- 22875316
TI  - The medical humanities and the perils of curricular integration.
AB  - The advent of integration as a feature of contemporary medical curricula can be
      seen as an advantage for the medical humanities in that it provides a clear
      implementation strategy for the inclusion of medical humanities content and/or
      perspectives, while also making its relevance to medical education more apparent.
      This paper discusses an example of integration of humanities content into a
      graduate medical course, raises questions about the desirability of an
      exclusively integrated approach, and argues for the value of retaining a discrete
      and coherent disciplinary presence for the medical humanities in medical
      curricula.

PMID- 22875317
TI  - Hospital prescribing:  it's all about the culture.

PMID- 22875318
TI  - Medical handovers:  an improvement opportunity.

PMID- 22875320
TI  - Electrophysiology and ablation of arrhythmias.
AB  - Major advances in diagnosis and treatment of arrhythmias have created the
      subspecialty of cardiac electrophysiology. This article reviews supraventricular
      and ventricular arrhythmias and outlines the indications and process of
      electrophysiological testing, arrhythmia mechanism and their treatment by
      catheter ablation.

PMID- 22875321
TI  - Heart disease in pregnancy.
AB  - In women with cardiac disease physiological changes in the cardiovascular system
      associated with pregnancy may precipitate decompensation. Heart disease is the
      commonest cause of maternal death. Close multidisciplinary working is important
      to ensure the best care possible for pregnant women with heart disease.

PMID- 22875322
TI  - Stress echocardiography vs nuclear stress imaging in clinical cardiology.
AB  - Stress echocardiography and nuclear stress imaging are important non-invasive
      tools in clinical cardiology. This review discusses the uses, strengths and
      limitations of these imaging modalities and looks at whether stress
      echocardiography can actually replace nuclear stress imaging.

PMID- 22875324
TI  - Managing pancreatoduodenal trauma.
AB  - Pancreatoduodenal injuries are an uncommon but important source of morbidity and
      mortality in the trauma patient. They require a multidisciplinary approach, with
      a pancreatic surgeon involved at the earliest opportunity. The investigation and
      management of these injuries are discussed along with the role of operative
      intervention.

PMID- 22875323
TI  - Depression in Parkinson's disease: diagnosis and management.
AB  - Parkinson's disease has a high prevalence of psychiatric comorbidity including
      depression. This review highlights the epidemiology, aetiology and diagnosis of
      depression in patients with Parkinson's disease. Recommendations are made on
      treatment and a closer partnership between neurology and psychiatry.

PMID- 22875325
TI  - Structured airway intervention improves safety of endotracheal intubation in an
      intensive care unit.
AB  - Each year the Royal College of Anaesthetists undertakes a national audit project
      of procedures and practices within the specialty that have the potential to be
      associated with significant morbidity and mortality. The fourth National Audit
      Project (NAP4), endorsed by the Difficult Airway Society, audited advanced airway
      management and its complications in general theatres, labour wards, critical care
      units and emergency departments. The NAP4 data allowed the authors to benchmark
      their own practice against national standards. Using the recommendations in NAP4
      they developed a quality improvement intervention to improve airway assessment
      and tracheal intubation procedures. The authors used a multidisciplinary team
      approach to training, improving resources and adopting new working practices,
      which resulted in improved endotracheal intubation technique, and embedded new
      practice and a new departmental training programme.

PMID- 22875326
TI  - Trainee doctors with learning difficulties: recognizing need and providing
      support.
AB  - Specific learning difficulties affect medical students and trainee doctors. These
      conditions impact on processing and learning skills, and are associated with
      positive attributes. Having an awareness of these is key for successful and
      effective medical educators.

PMID- 22875327
TI  - The retreat from Moscow: a medical catastrophe.

PMID- 22875328
TI  - Three cases of misdiagnosed skeletal lytic lesions: the mimicry of tuberculosis.

PMID- 22875330
TI  - Protect yourself as well as your property.

PMID- 22875329
TI  - Dignity and geriatrics.

PMID- 22875332
TI  - Ketamine for analgesia.

PMID- 22875333
TI  - Accelerated simulation study of space charge effects in quadrupole ion traps
      using GPU techniques.
AB  - Space charge effects play important roles in the performance of various types of
      mass analyzers. Simulation of space charge effects is often limited by the
      computation capability. In this study, we evaluate the method of using graphics
      processing unit (GPU) to accelerate ion trajectory simulation. Simulation using
      GPU has been compared with multi-core central processing unit (CPU), and an
      acceleration of about 390 times have been obtained using a single computer for
      simulation of up to 10(5) ions in quadrupole ion traps. Characteristics of
      trapped ions can be investigated at detailed levels within a reasonable
      simulation time. Space charge effects on the trapping capacities of linear and 3D
      ion traps, ion cloud shapes, ion motion frequency shift, mass spectrum peak
      coalescence effects between two ion clouds of close m/z are studied with the ion
      trajectory simulation using GPU.

PMID- 22875334
TI  - Ambient mass spectrometry imaging: a comparison of desorption ionization by sonic
      spray and electrospray.
AB  - Easy ambient sonic spray ionization (EASI) and desorption electrospray ionization
      (DESI) were used for imaging of a number of samples, including sections of rat
      brain and imprints of plant material on porous Teflon. A novel approach termed
      Displaced Dual-mode Imaging was utilized for the direct comparison of the two
      methods: Images were recorded with the individual rows alternating between EASI
      and DESI, yielding a separate image for each technique recorded under perfectly
      similar conditions on the same sample. EASI works reliably for imaging of all
      samples, but the choice of spray solvent and flow rate is more critical in tissue
      imaging with EASI than with DESI. The overall sensitivity of EASI is, in general,
      slightly lower than that of DESI, and the representation of the dynamic range is
      different in images of the two techniques for some samples. However, for abundant
      compounds, EASI works well, resulting in images of similar quality as DESI. EASI
      can thus be used in imaging experiments where the application of high voltage is
      impractical or undesirable. The present study is in its nature also a comparison
      of the characteristics of the two techniques, showing results also applicable for
      non-imaging work, with regards to sensitivity and experimental conditions.

PMID- 22875335
TI  - Monitoring therapy with MEK inhibitor U0126 in a novel Wilms tumor model in Wt1
      knockout Igf2 transgenic mice using 18F-FDG PET with dual-contrast enhanced CT
      and MRI: early metabolic response without inhibition of tumor growth.
AB  - PURPOSE: The understanding of the role of genetic alterations in Wilms tumor
      development could be greatly advanced using a genetically engineered mouse models
      that can replicate the development and progression of this disease in human
      patients and can be monitored using non-invasive structural and molecular imaging
      optimized for renal tumors. PROCEDURES: Repetitive dual-contrast computed
      tomography (CT; intravenous and intraperitoneal contrast), T2-weighted magnetic
      resonance imaging (MRI), and delayed 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F
      FDG) positron emission tomography (PET) were utilized for characterization of
      Igf2 biallelic expression/Wt1 knockout mouse model of Wilms tumor. For CT
      imaging, Ioversol 678 mg/ml in 200 MUl was administered i.p. followed by 100 MUl
      injected intravenously at 20 and 15 min prior to imaging, respectively. Static
      PET imaging studies were acquired at 1, 2, and 3 h after i.v. administration of
      (18)F-FDG (400 MUCi). Coronal and sagittal T1-weighted images (TE/TR 8.5/620 ms)
      were acquired before and immediately after i.v. injection of 0.4 ml/kg
      gadopentetate dimeglumine followed by T2-weighted images (TE/TR 60/300 ms). Tumor
      tissue samples were characterized by histopathology and immunohistochemistry for
      Glut1, FASN, Ki67, and CD34. In addition, six Wt1-Igf2 mice were treated with a
      mitogen-activated protein kinase (MEK) inhibitor U0126 (50 MUmol/kg i.p.) every 4
      days for 6 weeks. (18)F-FDG PET/CT imaging was repeated at different days after
      initiation of therapy with U0126. The percent change of initial tumor volume and
      SUV was compared to non-treated historic control animals. RESULTS: Overall, the
      best tumor-to-adjacent kidney contrast as well as soft tissue contrast for other
      abdominal organs was achieved using T2-weighted MRI. Delayed (18)F-FDG PET (3-h
      post (18)F-FDG administration) and dual-contrast CT (intravenous and
      intraperitoneal contrast) provided a more accurate anatomic and metabolic
      characterization of Wilms tumors in Wt1-Igf2 mice during early development and
      progression of renal tumors. Over the 8-month period, 46 Wt1-Igf2 mice and 8
      littermate control mice were studied. Renal tumors were identified in 54.3 % of
      Wt1-Igf2 mice between post-natal 50-100 days. In 35.6 % of Wt1-Igf2 mice, tumors
      were localized in the right kidney; in 24 %, in the left kidney, while 40.4 % of
      Wt1-Igf2 mice had bilateral kidney tumors. Metastatic lesions were identified in
      15.4 % of Wt1-Igf2 mice. Increased levels of Glut1 and IGF1R expression, high
      Ki67 labeling index, and a dense network of CD34+ microvessels in renal tumors
      was consistent with increased (18)F-FDG accumulation. Treatment with a MEK 1/2
      inhibitor U0126 did not cause the inhibition of tumor growth as compared to
      untreated animals. However, after the first three to four doses (~2 weeks of
      treatment), a decrease in (18)F-FDG SUV was observed, as compared to pre
      treatment levels (p < 0.05, paired Student t test), which constitutes a metabolic
      response. Six weeks later, despite continuing therapy, the (18)F-FDG SUV
      increased again to previous levels. CONCLUSIONS: The optimized dual contrast
      PET/CT imaging with early post i.v. and i.p. contrast CT and 3 h delayed PET
      imaging after (18)F-FDG administration provides a sensitive and reliable method
      for detecting early tumor lesions in this endogenous mouse model of Wilms tumor
      and for monitoring their growth in response to targeted therapies. Therapy with
      MEK inhibitor U0126 produces only a transient inhibition of tumor glycolytic
      activity but does not inhibit tumor growth, which is due to continuing IGF2
      induced signaling from IGF1R through the PI3K-AKT-mTOR pathway.

PMID- 22875336
TI  - Measuring the nursing workload per shift in the ICU.
AB  - PURPOSE: In the intensive care unit (ICU) different strategies and workload
      measurement tools exist to indicate the number of nurses needed. The gathered
      information is always focused on manpower needed per 24 h. However, a day
      consists of several shifts, which may be unequal in nursing workload. The aim of
      this study was to evaluate if differences in nursing workload between consecutive
      shifts can be identified by a nursing workload measurement tool. METHODS: The
      nursing activities score (NAS) was registered per patient for every shift during
      a 4-week period in a prospective, observational research project in the surgical
      pediatric ICU (SICU-PICU) and medical ICU (MICU) of an academic hospital.
      RESULTS: The NAS was influenced by the patient characteristics and the type of
      shift. Furthermore, the scores were lower during night shifts, in weekends and in
      MICU patients. Overall, the mean NAS per nurse per shift was 85.5 %, and the NAS
      per 24 h was 54.7 %. CONCLUSION: This study has shown that the nursing workload
      can be measured per working shift. In the ICU, the NAS differentiates the nursing
      workload between shifts, patients and units.

PMID- 22875337
TI  - The continuing imperative to measure workload in ICU: impact on patient safety
      and staff well-being.

PMID- 22875339
TI  - Blunted renal dopaminergic system in a mouse model of diet-induced obesity.
AB  - Obesity has reached epidemic proportions in the Western world and is implicated
      in the pathophysiology of essential hypertension. The aim of the present study
      was to evaluate sodium handling, blood pressure and renal dopaminergic system
      activity in a mouse model of obesity induced by exposure to a hypercaloric diet.
      From six to 18 weeks of age, animals were fed with a control diet or a high-fat
      high-simple-carbohydrate (HFHSC) diet. Renal function, blood pressure and urinary
      and plasmatic catecholamines and biochemical parameters were evaluated in both
      groups. In parallel, the effects of high sodium intake (HS, 1.0% NaCl, 3 days) on
      natriuresis, urinary catecholamine excretion and aromatic l-amino acid
      decarboxylase (AADC) activity were evaluated in control and obese mice. Mice
      exposed to the HFHSC diet presented obesity, hyperglycemia, glucose intolerance,
      insulin resistance, hyperinsulinemia and increased blood pressure. This was
      accompanied, in obese mice, by decreases in urinary excretion of dopamine and
      metabolites as well as reduced AADC activity in renal tissues. During HS intake,
      absolute urinary dopamine excretion increased in control, but not in obese mice.
      This was accompanied in obese mice by a natriuretic resistance on day 1 of the HS
      diet. In addition, obese mice presented increased urinary and plasmatic
      noradrenaline levels, as well as an increased heart rate when compared with
      control mice. In conclusion, in this model of diet-induced obesity
      hyperinsulinemia, insulin resistance and increased sympathetic tone are
      associated with blunted renal dopaminergic activity. It is suggested that this
      may contribute to compromised sodium excretion and increased blood pressure in
      obesity.

PMID- 22875340
TI  - Resveratrol promotes neurotrophic factor release from astroglia.
AB  - Neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF)
      and brain-derived neurotrophic factor (BDNF) are considered to contribute to the
      development, maintenance and survival of neurons, glia and oligodendrocytes.
      Astroglia are a major source of various neurotrophic factors. Thus, enhancement
      of astroglia-mediated neurotrophic factor release might hold promising potential
      for neurological diseases. Resveratrol, a natural non-flavonoid polyphenol found
      in grapes and red wine, has been recognized to be beneficial for health. Here,
      rat primary astroglia-enriched cultures were used to investigate the effects of
      resveratrol-mediated neurotrophic factor release and the related mechanisms. The
      cultures were treated with 25-100 MUmmol/L resveratrol for 12-48 h. Results
      showed resveratrol increased BDNF and GDNF production in the culture medium. In
      addition, the production of BDNF in the supernatant of cultures was increased
      five-fold over control cultures 24 h after resveratrol treatment and then
      remained high 36 h later. Meanwhile, the production of GDNF was initially
      increased by up to four-fold 24 h after resveratrol treatment and continued to
      increase to six-fold at 36 h and remained at a high level till 48 h. Western blot
      analysis of BDNF and GDNF protein in astroglia at different time points after
      resveratrol treatment indicated similar increases. Furthermore, resveratrol
      significantly induced the phosphorylation of extracellular signal-regulated
      kinase 1/2 (ERK1/2) and cAMP responsive element-binding protein (CREB) in
      astroglia. Overall, resveratrol is effective in promoting astroglia-derived
      neurotrophic factor release, and this effect is mediated, at least in part, by
      the activation of ERK1/2 and CREB.

PMID- 22875338
TI  - Elevated preoperative serum asymmetrical dimethylarginine (ADMA) is associated
      with poor outcomes after pediatric cardiac surgery.
AB  - PURPOSE: Asymmetrical dimethylarginine (ADMA), an endogenous competitive
      inhibitor of nitric oxide synthase, is elevated in vascular pathologies such as
      hypertension and chronic kidney disease. Children undergoing cardiac surgery are
      at high risk of poor hemodynamic and renal outcomes secondary to cardiopulmonary
      bypass (CPB). This study tested the hypothesis that elevated preoperative ADMA
      levels are associated with overall worse clinical outcomes after pediatric CPB.
      METHODS: This was a prospective, observational study of 100 patients aged from 2
      weeks to 18 years who underwent cardiac surgery involving CPB. Serum ADMA levels
      were obtained preoperatively and on postoperative days zero through four.
      Clinical outcomes measured included acute kidney injury (AKI) by pRIFLE criteria,
      low cardiac output syndrome (LCOS), length of mechanical ventilation, hospital
      and ICU length of stay, unplanned reoperation, and mortality. RESULTS: The 29
      patients with an elevated preoperative ADMA were more likely to have prolonged
      mechanical ventilation, increased ICU and hospital length of stay, unplanned
      reoperation, and LCOS than those with a normal preoperative level. ADMA levels
      inversely correlated with estimated glomerular filtration rate (eGFR), but did
      not differ between patients with and without AKI after CPB. Preoperative ADMA
      levels correlated with hospital length of stay (r(s) = 0.289), ICU length of stay
      (r(s) = 0.308), and length of mechanical ventilation (r(s) = 0.402); [all p <
      0.05]. ADMA levels before surgery had good predictive power for prolonged
      mechanical ventilation (AUC-ROC 0.809; 95 % CI 0.704, 0.914; p < 0.001).
      CONCLUSIONS: Patients with elevated ADMA before surgery were more likely to have
      prolonged mechanical ventilation, develop LCOS, require an extended length of
      stay, and require reoperation. ADMA levels inversely correlated with eGFR, but
      did not predict AKI. Preoperative serum ADMA appears to identify pediatric
      cardiac surgery patients at risk of poor postoperative outcomes following CPB.

PMID- 22875341
TI  - Prenatal and early postnatal exposure to high-saturated-fat diet represses Wnt
      signaling and myogenic genes in offspring rats.
AB  - The prenatal and early postnatal period is a key developmental window for
      nutrition status, and high-fat exposure in this period has been shown to be
      associated with type 2 diabetes, obesity and other features of metabolic
      disorders later in life. The present study was designed to investigate the
      underlying molecular mechanisms and role of relative genes involved in this
      process. We investigated the impact of prenatal and early postnatal exposure to a
      high-saturated-fat diet on the regulation of the Wnt signaling pathway and
      myogenic genes in skeletal muscle of rat offspring as well as the serum and
      muscle physiological outcomes. Timed-pregnant Sprague-Dawley rats were fed either
      a control (C, 16% kcal fat) or high-saturated-fat diet (HF, 45% kcal fat)
      throughout gestation and lactation. After weaning, female offspring were fed a
      control diet to generate two offspring groups: control diet-fed offspring of
      control diet-fed dams (C/C) and control diet-fed offspring of HF diet-fed dams
      (HF/C). The serum glucose of the HF/C offspring (5.58 +/- 0.26 mmol/L) was
      significantly higher than that of C/C offspring (4.97 +/- 0.28 mmol/L), and the
      Homeostasis Model Assessment-Insulin Resistance of HF/C offspring (2.00 +/- 0.11)
      was also significantly higher when compared with C/C (1.84 +/- 0.09).
      Furthermore, HF/C offspring presented excessive intramuscular fat accumulation
      (1.8-fold, P < 0.05) and decreased muscle glycogen (1.3-fold, P < 0.05), as well
      as impairment of muscle development at the age of 12 weeks. Meanwhile, we
      observed the repression of Wnt/beta-catenin signaling and myogenic genes in HF/C
      offspring. The present study indicates that prenatal and early postnatal exposure
      to a high-saturated-fat diet suppresses the development of skeletal muscle and
      myogenic genes via Wnt/beta-catenin signaling, and the inappropriate muscle
      development could potentially contribute to the predisposition of offspring to
      develop metabolic-syndrome-like phenotype in adulthood.

PMID- 22875342
TI  - Norisoboldine, an alkaloid compound isolated from Radix Linderae, inhibits
      synovial angiogenesis in adjuvant-induced arthritis rats by moderating Notch1
      pathway-related endothelial tip cell phenotype.
AB  - Synovial angiogenesis is well recognized as participating in the pathogenesis of
      rheumatoid arthritis (RA) and has been regarded as a potential target for RA
      therapy. Previously, we have shown that norisoboldine (NOR) can protect joints
      from destruction in mice with collagen II-induced arthritis (CIA). Here, we
      investigate the effect of NOR on synovial angiogenesis in adjuvant-induced
      arthritis (AA) rats, and clarify the mechanisms in vitro. NOR, administered
      orally, significantly reduced the number of blood vessels and expression of
      growth factors in the synovium of AA rats. In vitro, it markedly prevented the
      migration and sprouting of endothelial cells. Notably, the endothelial tip cell
      phenotype, which is essential for the migration of endothelial cells and
      subsequent angiogenesis, was significantly inhibited by NOR. This inhibitory
      effect was attenuated by pretreatment with N-{N-[2-(3,5-difluorophenyl) acetyl]
      (S)-alanyl}-(S)-phenylglycine tert-butyl ester, a Notch1 inhibitor, suggesting
      that the action of NOR was related to the Notch1 pathway. A molecular docking
      study further confirmed that NOR was able to promote Notch1 activation by binding
      the Notch1 transcription complex. In conclusion, NOR was able to prevent synovial
      angiogenesis in AA rats, which is a putatively new mechanism responsible for its
      anti-rheumatoid effect. The anti-angiogenesis action of NOR was likely achieved
      by moderating the Notch1 pathway-related endothelial tip cell phenotype with a
      potential action target of the Notch1 transcription complex.

PMID- 22875343
TI  - Raf/MEK/ERK signaling inhibition enhances the ability of dequalinium to induce
      apoptosis in the human leukemic cell line K562.
AB  - Delocalized lipophilic cations, such as dequalinium (DQA), selectively accumulate
      in mitochondria and display anticancer activity in cells from different
      malignancies. Previous studies in K562 human leukemic cells indicate that DQA
      causes cell damage as a consequence of an early disturbance in the mitochondrial
      function, inducing oxidative stress. These cells turned out to be resistant to
      apoptosis and died by necrosis when treated with high DQA concentrations (20
      MUmol/L) for long time periods (48 h). Resistance of K562 cells to DQA-induced
      apoptosis could be eliminated by inhibition of the kinase activity of the Bcr-Abl
      protein with imatinib. In this paper, we have studied the effect of DQA on the
      Raf/MEK/ERK1/2 and PI3K/Akt signal transduction pathways in K562 cells. Our data
      suggest a DQA downregulatory activity on both ERK1/2 and PI3K protein kinase
      activity supporting an interaction between both proteins. Moreover, inhibition of
      ERK1/2 with U0126 enhanced the ability of DQA to potentiate imatinib-induced
      apoptosis, suggesting a role of the Raf/MEK/ERK pathway and the Bcr-Abl tyrosine
      kinase in the K562 cell survival. This study contributes to a better
      understanding of the action mechanism of DQA on K562 cells and encourages the
      study of DQA in combination with other agents for improving the efficacy of
      targeted therapies and overcoming resistance to chemotherapeutic agents.

PMID- 22875344
TI  - Role of chymase in diabetic nephropathy.
AB  - Chymase is an alternative pathway for angiotensin-converting enzyme in
      angiotensin II (Ang II) formation, and its expression is increased in human
      diabetic kidneys and in human mesangial cells (MCs) stimulated with high glucose.
      In addition, chymase activates transforming growth factor (TGF-beta1) via an Ang
      II-independent pathway. The aim of this study was to evaluate the role of chymase
      on TGF-beta1 activation in diabetic rats and in rat MCs (RMCs) stimulated with
      high glucose (HG). Diabetes was induced in male Wistar rats by streptozotocin (60
      mg/kg, intravenous). After 30 (D30) or 60 (D60) days, chymase activity and the
      expression of profibrotic markers were evaluated. RMCs were stimulated with HG in
      the presence or absence of 50 MUmol/L chymostatin, a chymase inhibitor, or 100
      nmol/L of losartan, an Ang II antagonist. Chymase activity and expression
      increased in D60 kidneys, with increased expression of fibronectin, type I and
      III collagen, TGF-beta1 and Smad 3 and with no change in Smad 7 expression. RMCs
      exposed to HG presented increases in chymase activity and expression, together
      with upregulation in fibrosis markers and in the TGF-beta1 signaling pathway. All
      these effects were reversed by chymostatin and by losartan, but type 1
      angiotensin II receptor blockade did not interfere with the Smad 3 and 7 pathway.
      Similar to HG-stimulated RMCs, control RMCs treated with chymase responded with
      increased expression of TGF-beta1, Smad 3 and fibrosis markers. These effects
      were reversed by chymostatin but not by losartan. The results indicate an
      important role for chymase in inducing fibrosis through TGF-beta1 activation,
      parallel with Ang II effects.

PMID- 22875346
TI  - 'The student nurse of today  is the staff nurse of tomorrow'.

PMID- 22875345
TI  - Supramolecular hydrogel of kanamycin selectively sequesters 16S rRNA.
AB  - As the first example of hydrogelator derived from aminoglycoside antibiotics, the
      hydrogel of kanamycin indicates that the hydrogel of aminoglycosides preserve the
      specific interaction with their macromolecular targets (e.g., 16S rRNA), thus
      illustrating a simple approach to explore and identify possible biological
      targets of supramolecular nanofibers/hydrogels.

PMID- 22875347
TI  - Carers Week: unpaid, but as professional as they come.

PMID- 22875348
TI  - Management of occupational  blood exposures: a 4-year review.
AB  - In the healthcare setting, occupational blood exposure (OBE) is a well recognised
      hazard. Following exposure, prompt and correct management is required to prevent
      infection and minimise adverse psychological impact. The aim of the study was to
      ascertain whether or not documentation of the management and follow up of OBEs
      was appropriate and in line with best practice. Of the 134 cases reviewed, 65% of
      staff who reported an OBE attended for management on the day of the injury. The
      instrument type was documented in 95% of cases, and degree of injury in 91%.
      However, the provision of first aid was adequately documented for only 36% of
      exposure cases and the provision of adequate information and advice was
      documented for just 33%. Only approximately half of 23% of healthcare workers
      requiring follow up completed this within the recommended time frame. This study
      identified deficits in documentation, communication and follow up. However, this
      will likely improve with the recommendations outlined in this article.

PMID- 22875349
TI  - Washing and changing uniforms:  is guidance being adhered to?
AB  - To allay public apprehension regarding the risk of nurses' uniforms transmitting
      healthcare-associated infections (HCAI), national and local guidelines have been
      issued to control use, laundry and storage. This paper aims to measure the
      knowledge of registered nurses (RNs) and healthcare assistants (HCAs) working
      within a rural NHS foundation Trust and their adherence to the local infection
      prevention and control (IPC) standard regarding uniforms through a Trust-wide
      audit. Stratified random sampling selected 597 nursing staff and 399 responded
      (67%) by completing a short questionnaire based on the local standard. Responses
      were coded and transferred to SPSS (v. 17) for analysis. The audit found that
      nursing staff generally adhere to the guidelines, changing their uniforms daily
      and immediately upon accidental soiling, and wearing plastic aprons where
      indicated. At home, staff normally machine-wash and then iron their uniforms at
      the hottest setting. Nevertheless, few observe the local direction to place their
      newly-laundered uniforms in protective covers. This paper recommends a re-audit
      to compare compliance rates with baseline figures and further research into the
      reasons why compliance is lacking to sanction interventions for improvement, such
      as providing relevant staff education and re-introducing appropriate changing
      facilities.

PMID- 22875350
TI  - Catheter-associated urinary  tract infections in women.

PMID- 22875351
TI  - Climbing the walls: prison mental health and community engagement.
AB  - Until recently, treatment for mental health conditions has focused on medical and
      psychological therapy. The role and significance of social and community
      interventions and initiatives in fostering recovery, resilience and a sense of
      'flourishing' is now being recognised. This paper seeks to explore how these
      principles, which are usually community-based, can be successfully applied within
      a prison setting, and how such interventions may have a positive effect on the
      mental health of prisoners through successfully engaging them with the
      communities they are set to return to after release while still in custody.

PMID- 22875352
TI  - Disclosing HIV status to HIV positive children before adolescence.
AB  - This literature review aims to explore the importance of disclosing HIV status to
      HIV positive children before they reach adolescence. Since the use of paediatric
      highly active antiretroviral therapy, many HIV positive children are now
      surviving into adulthood. This faces parents and healthcare workers with the
      difficult process of disclosing HIV status to children. A review of the
      literature has revealed discussions of the following themes: barriers to HIV
      disclosure before adolescence; disclosure as a process, rather than a one-off
      event; and the benefits of and need for HIV disclosure before adolescence.
      Parental beliefs and anxieties were found to be the main barrier to HIV
      disclosure and this needs to be addressed through education and governmental
      policies (Department of Health (DH), 2007). HIV disclosure before adolescence is
      vital, as a lack of communication about HIV creates confusion and mistrust, harms
      psychosocial development, compromises the child's right to autonomy and increases
      the risk of uknowingly transmitting the disease.

PMID- 22875353
TI  - The use of complementary  and alternative medicine by nurses.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use is common among
      patients attending the department of the authors of this article. With expanding
      roles of nurses in various clinics, the nurses are often asked for their advice
      on CAM use by their patients. CAM education is not part of the nursing curriculum
      in various parts of the world. The aim of this study was to establish the use of
      CAM by nurses along with their knowledge base and attitudes towards it. METHODS:
      A questionnaire-based study based on the published literature was used among
      qualified nurses. The data were collected and analysed using SPSS for Windows.
      RESULTS: The response rate was 86% (531/621; females were 91% and the mean age
      was 32 years (range 20-63). Eighty percent of the responders admitted to use of
      CAM and 41% were using CAM at the time. The most commonly mentioned CAM were
      massage, cod liver oil and cranberry juice. CAM was mostly used for relaxation,
      joint pain and urinary tract infection. Only five nurses believed CAM was not
      effective and 74% would recommend CAM use to others. Ninety-three percent of
      nurses did not have any formal education on CAM. Most nurses would consider some
      education on CAM to enable them to counsel their patients. CONCLUSIONS: The use
      of CAM is high among nurses. As patients are increasingly relying on nurses for
      advice on its use, it is important for nurses to be educated about CAM in order
      to guide their patients.

PMID- 22875356
TI  - Final-year student nurses' perceptions of role transition.
AB  - Role transition can be both challenging and exciting. This study presents the
      findings of phase one of a two-part study conducted by Deasy et al (2011), which
      explored final-year student nurses' (n=116) perceptions and expectations of role
      transition. The students were registered on four-year BSc nursing programmes at
      an Irish university. Data was analyzed using SPSS (version 16). A response rate
      of 84% was achieved. Over half of respondents said they were adequately prepared
      for the post of registered nurse. Respondents generally perceived themselves to
      be competent across a range of domains: managing workloads; prioritizing care
      delivery; interpersonal skills; time management skills; ethical decision making;
      and providing health information and education. In contrast, not all were
      confident about their knowledge and many expected the transition to be
      problematic. Most expected to be supported and to receive constructive feedback.
      Recommendations include nurturing supportive work environments to reduce stress
      and increase confidence.

PMID- 22875355
TI  - Safety Express: a strategic  health authority's approach.
AB  - The Safety Express programme is a national workstream within the Quality,
      Innovation, Productivity and Prevention (QIPP) programme that is designed to
      improve health outcomes and quality care, as well as reduce costs associated with
      the following four patient harms: pressure ulcers, falls, urinary tract
      infections in patients with catheters and venous thromboembolism (VTE). NHS
      London developed a pilot project to implement Safety Express across London. This
      paper presents case studies of the outcomes of the Safety Express pilot in three
      locations in London. Findings from the pilot showed that the proportion of
      patients who were harm-free from pressure ulcers, falls, urinary infections (in
      patients with a catheter) and new VTE compares favourably with the national
      average, with an overall decrease in all four.

PMID- 22875357
TI  - Is poor care cause for concern  in nurse education?

PMID- 22875358
TI  - National Diabetes  Inpatient Audit: implications.

PMID- 22875359
TI  - NMC 'lacks clear vision of role':  CHRE publishes interim report.

PMID- 22875360
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 1: the
      difference between the two.

PMID- 22875361
TI  - Setting the pace for change: a strengthened commitment.

PMID- 22875362
TI  - TOFwave: reproducibility in biomarker discovery from time-of-flight mass
      spectrometry data.
AB  - Many are the sources of variability that can affect reproducibility of disease
      biomarkers from time-of-flight (TOF) Mass Spectrometry (MS) data. Here we present
      TOFwave, a complete software pipeline for TOF-MS biomarker identification, that
      limits the impact of parameter tuning along the whole chain of preprocessing and
      model selection modules. Peak profiles are obtained by a preprocessing based on
      Continuous Wavelet Transform (CWT), coupled with a machine learning protocol
      aimed at avoiding selection bias effects. Only two parameters (minimum peak width
      and a signal to noise cutoff) have to be explicitly set. The TOFwave pipeline is
      built on top of the mlpy Python package. Examples on Matrix-Assisted Laser
      Desorption and Ionization (MALDI) TOF datasets are presented. Software prototype,
      datasets and details to replicate results in this paper can be found at
      http://mlpy.sf.net/tofwave/.

PMID- 22875363
TI  - From bad to worse: a note on human trafficking.

PMID- 22875365
TI  - An introduction to patient decision aids.
AB  - Patient decision aids are a means of helping people make informed choices about
      healthcare that take into account their personal values and preferences. Decision
      aids are a part of a shared decision-making process, encouraging active
      participation by patients in healthcare decisions.(1,2) Decision aids are
      relevant in many common healthcare decisions. They have been developed to make it
      easier for patients and healthcare professionals to discuss treatment options.
      Here, we give an overview of the rationale for the use of patient decision aids,
      what they contain, the evidence of their efficacy and examples of their current
      and potential uses.

PMID- 22875364
TI  - One SNP in the 3'-UTR of HMGB1 gene affects the binding of target bta-miR-223 and
      is involved in mastitis in dairy cattle.
AB  - High-mobility group box protein 1 (HMGB1) gene has a universal sentinel function
      for nucleic acid-mediated innate immune responses and acts as a pathogenic
      mediator in the inflammatory disease. In an effort to identify the functional
      single-nucleotide polymorphism (SNP) in the 3'-untranslated region (UTR) of the
      bovine HMGB1 gene that affects the binding to its target microRNA, first, the
      expression of HMGB1 mRNA in different genotypes and its candidate bta-miR-223 was
      investigated. Quantitative real-time polymerase chain reaction results showed
      that the relative expression of HMGB1 mRNA in cows with the genotype GG is
      significantly higher than those in cows with the genotype AA (P < 0.05). The
      expression of bta-miR-223 was significantly upregulated by 1.95-fold (P < 0.05)
      in the bovine mastitis-infected mammary gland tissues compared with that in the
      healthy tissues. Subsequently, luciferase assay indicated that the HMGB1
      expression was directly targeted by bta-miR-223 in human embryo kidney 293 T (HEK
      293T) cells. One novel SNP (g. +2776 A > G) in the HMGB1 3'-UTR, altering the
      binding of HMGB1 and bta-miR-223, was found to be associated with somatic count
      scores in cows. Taken together, the g. +2776 A > G-GG was an advantageous
      genotype which can be used as a candidate functional marker for mastitis
      resistance breeding program.

PMID- 22875366
TI  - Management of chronic Achilles tendinopathy.
AB  - Tendons transmit force between muscles and bones and, when stretched, store
      elastic energy that contributes to movement.(1) The tendinous portion of the
      gastrocnemius and soleus muscles merge to form the Achilles tendon, which is the
      largest and strongest in the body, but one of the most frequently injured.(2,3)
      Conservative management options for chronic Achilles tendinopathy include
      eccentric (lengthening) exercises, extracorporeal shockwave therapy (ESWT),
      topical nitroglycerin, low level laser therapy, orthoses, splints or injections
      (e.g. corticosteroids, hyperosmolar dextrose, polidocanol, platelet-rich plasma),
      while a minority of patients require surgery (using open, percutaneous or
      endoscopic methods).(4-8) Here we assess the management options for patients with
      chronic Achilles tendinopathy (lasting over 6 weeks).

PMID- 22875367
TI  - Risk of herbicide mixtures as a key parameter to explain phytoplankton
      fluctuation in a great lake: the case of Lake Geneva, Switzerland.
AB  - Mixture risk assessment predictions have rarely been confronted with biological
      changes observed in the environment. In this study, long-term monitoring of a
      European great lake, Lake Geneva, provides the opportunity to assess to what
      extent the predicted toxicity of herbicide mixtures explains the changes in the
      composition of the phytoplankton community next to other classical limnology
      parameters such as nutrients. To reach this goal, the gradient of the mixture
      toxicity of 14 herbicides regularly detected in the lake was calculated using
      concentration addition and response addition models. A temporal gradient of
      toxicity was observed which decreased from 2004 to 2009. Redundancy analysis and
      partial redundancy analysis showed that this gradient explains a significant
      portion of the variation in phytoplankton community composition with and without
      having removed the effect of all other co-variables. Moreover, species that are
      significantly influenced, positively or negatively, by the decrease of toxicity
      in the lake over time are highlighted. It can be concluded that the herbicide
      mixture toxicity is one of the key parameters to explain phytoplankton changes in
      Lake Geneva.

PMID- 22875368
TI  - In vitro to in vivo extrapolation and species response comparisons for drug
      induced liver injury (DILI) using DILIsymTM: a mechanistic, mathematical model of
      DILI.
AB  - Drug-induced liver injury (DILI) is not only a major concern for all patients
      requiring drug therapy, but also for the pharmaceutical industry. Many new in
      vitro assays and pre-clinical animal models are being developed to help screen
      compounds for the potential to cause DILI. This study demonstrates that
      mechanistic, mathematical modeling offers a method for interpreting and
      extrapolating results. The DILIsymTM model (version 1A), a mathematical
      representation of DILI, was combined with in vitro data for the model
      hepatotoxicant methapyrilene (MP) to carry out an in vitro to in vivo
      extrapolation. In addition, simulations comparing DILI responses across species
      illustrated how modeling can aid in selecting the most appropriate pre-clinical
      species for safety testing results relevant to humans. The parameter inputs used
      to predict DILI for MP were restricted to in vitro inputs solely related to ADME
      (absorption, distribution, metabolism, elimination) processes. MP toxicity was
      correctly predicted to occur in rats, but was not apparent in the simulations for
      humans and mice (consistent with literature). When the hepatotoxicity of MP and
      acetaminophen (APAP) was compared across rats, mice, and humans at an equivalent
      dose, the species most susceptible to APAP was not susceptible to MP, and vice
      versa. Furthermore, consideration of variability in simulated population samples
      (SimPopsTM) provided confidence in the predictions and allowed examination of the
      biological parameters most predictive of outcome. Differences in model
      sensitivity to the parameters were related to species differences, but the
      severity of DILI for each drug/species combination was also an important factor.

PMID- 22875369
TI  - Incidence and risk factors for medial tibial stress syndrome and tibial stress
      fracture in high school runners.
AB  - PURPOSE: Medial tibial stress syndrome (MTSS) and tibial stress fracture (SF) are
      common lower leg disorders in runners. A prospective study was done to identify
      the incidence of MTSS and SF in high school runners and to determine risk
      factors. METHODS: A total of 230 runners participating in high school running
      teams were evaluated. All runners aged 15 years as first grade of high school
      were involved in the study. They were followed up for 3 years. The measured items
      included height, weight, body mass index (BMI), range of hip and ankle motion,
      straight leg raising (SLR), intercondylar and intermalleolar interval, Q-angle,
      navicular drop test, hip abductor strength and physical conditioning. Each runner
      was followed for 3 years to report occurrence of MTSS and SF. RESULTS: A total
      number of 102 MTSS (0.29 athlete exposures) and 21 SF (0.06 athlete exposures)
      were identified. In females, BMI significantly increased the risk of MTSS after
      adjustment for the other variables in this study (adjusted odds ratio, 0.51; 95 %
      confidence interval, 0.31-0.86). Increased internal rotation of the hip
      significantly increased the risk of MTSS (adjusted odds ratio, 0.91; 95 %
      confidence interval, 0.85-0.99). In males, limited SLR also significantly
      increased the risk of SF with adjustment for the other variables in this study
      (adjusted odds ratio, 1.38; 95 % confidence interval, 1.04-1.83). CONCLUSION: A
      significant relationship was found between BMI, internal hip rotation angle and
      MTSS in females, and between limited SLR and SF in males. LEVEL OF EVIDENCE:
      Prospective cohort study, Level II.

PMID- 22875370
TI  - Variations in ankle registration using two different anatomic landmarks: a
      radiographic study.
AB  - PURPOSE: To quantify the average deviation in tibial mechanical axis registration
      when registering the ankle centre using (a) the extreme medial and lateral points
      and (b) the most distal points, of the respective malleoli, and to identify
      whether body mass index (BMI) had any significant effect on mechanical axis
      registration error. METHODS: The preoperative standing hip-knee-ankle radiographs
      of 40 patients who underwent navigated TKR at our institution were reviewed. The
      divergence from the anatomic ankle centre in degrees and millimetres was compared
      when using the Extremes Midpoint and the Distal Midpoint techniques. RESULTS: No
      significant divergence was measured with either the Extremes Midpoint (0.2
      degrees  lateral, SD = 0.5 degrees ; 1.1 mm lateral, SD = 2.6 mm) or the Distal
      Midpoint (0.2 degrees  lateral, SD = 0.6 degrees ; 1.7 mm lateral, SD = 2.3 mm)
      techniques. BMI had no significant effect on these differences. CONCLUSIONS: Both
      the Extremes Midpoint and the Distal Midpoint techniques offer accurate
      registration of the ankle centre. BMI does not seem to affect the registration of
      the ankle centre with either technique. The findings of this study will help knee
      surgeons when choosing an ankle registration technique. These results may also
      lead to more accurate knee replacement navigation systems.

PMID- 22875371
TI  - Nutrition for wound healing.
AB  - The importance of the role of nutrition in wound healing is an area that has been
      widely explored over the last decade. It is well recognised that both
      macronutrients (protein, fat and carbohydrate) and micronutrients (vitamins,
      minerals and trace elements) play important parts in the healing of both chronic
      wounds and acute injuries. The term 'wound' encompasses many different situations
      from leg ulcers to laparostomy wounds. This article provides an overview of the
      role of different nutrients in the healing of wounds and guidance to nurses on
      first-line assessments, which can be used to ensure the patient is receiving
      adequate nutrition for successful wound healing. It will focus on commonly seen
      wounds in primary and secondary care but will not cover specialist wound
      management, such as laparostomy sites and burns, as these must always be cared
      for by experienced and specialist multidisciplinary teams.

PMID- 22875372
TI  - PHMB: an effective antimicrobial  in wound bioburden management.
AB  - The effective management of bacterial bioburden is an essential element of wound
      care. Recent years have seen the increased use of topical antimicrobial dressings
      to control colonisation and infection, yet there is concern that some may inhibit
      wound healing and may have systemic sequelae (World Union of Wound Healing
      Societies (WUWHS), 2008). This article focuses on the safety and effectiveness of
      PHMB, an antimicrobial compound that is relatively underused in the UK, and
      argues that it is an effective option for the management of bacterial
      colonisation and infection.

PMID- 22875373
TI  - Superabsorbent dressings  for copiously exuding wounds.
AB  - Exudate control is important in the management of both acute and chronic wounds.
      A new category of absorbent dressings that contain superabsorbent particles
      promises high absorbency. The aim of this multicentre, prospective, non
      comparative observational study was to evaluate the clinical efficacy and
      absorbent capacity of a superabsorbent dressing. Fifteen inpatients and
      outpatients with highly exuding wounds were included. Most patients (n=8) (53%)
      had chronic wounds; 20% (n=3) had ulcerating tumours. The superabsorbent dressing
      was used as a primary or a secondary dressing. Assessment was on day 0 (start),
      day 3 and day 7 (end of study). The study looked at wound bed and periwound skin
      condition, exudate production, pain upon dressing removal, reason for dressing
      removal, and frequency of dressing changes. A clinical visual scoring tool was
      used, together with digital photographs, which were assessed by the same
      experienced clinician. All 15 patients completed the study, during which no
      adverse events were noted. At day 7, maceration had reduced from 46.7% (n=7) at
      day 0 to 6.7% (n=1). After only 3 days, dressing change frequency was reduced
      from once daily to twice weekly in 80% (n=12) of patients. The superabsorbent
      dressing seems to reduce complications associated with exudate production,
      stimulate wound healing and increase patient comfort; it may also save time and
      costs for caregivers.

PMID- 22875374
TI  - Prevention of bilateral amputation  in a non-concordant patient.
AB  - As chronic wounds, venous leg ulcers (VLUs) are costly and impact significantly
      on a patient's quality of life. This case study focuses on the key considerations
      for wound management of bilateral venous leg ulcers in a 45-year-old mother who
      had undergone multiple admissions with sepsis secondary to the ulcers and whose
      life was considered at risk. The primary concern was to stabilise the patient,
      and then to determine the aetiology of the leg ulcers and develop a treatment
      plan. Kerraboot (Crawford Healthcare) was chosen to dress the wound initially as
      it is relatively quick and easy to apply while being atraumatic, manages exudate
      and facilitates autolytic debridement (Harvey, 2006). After 12 days debridement
      was complete and granulation tissue was observed to the skin surface level. At
      this time, the patient's condition had stabilised and the wound aetiology could
      then be determined. The ulcers were confirmed as venous and were subsequently
      managed with compression bandaging. They continued to heal, reducing in size by
      60% after a further 3 months. By agreeing a highly individualised wound treatment
      plan with the patient that was tailored to both her needs and those of the wound,
      and by continually reviewing and revising this plan, bilateral amputation was
      avoided in this previously non-concordant patient.

PMID- 22875375
TI  - RCTs best for evidence on wound care: fact or fiction?

PMID- 22875376
TI  - Pressure ulcer incidence among high-risk inpatients in Nigeria.
AB  - This main aim of this study was to determine the incidence of pressure ulcers
      among inpatients in selected hospitals in South West Nigeria. It also aimed to
      determine the body parts most susceptible to pressure ulcers. The study used a
      questionnaire completed by health workers in five hospitals, and 318 patients
      took part. Statistical methods used included descriptive statistics and non
      parametric inferential statistics. Within the 12-week follow-up period, 44
      patients developed nosocomial pressure ulcer(s). Inpatients with spinal cord
      injury (50%), orthopaedic (38.6%) and head injury (11.4%) related diagnoses were
      the most prone to developing pressure ulcers. The commonest areas where pressure
      ulcers developed were the sacrum, heel, greater trochanter and lateral and medial
      malleoli. The median time for the skin to develop an ulcer was 25 days after
      admission. There was a significant association between diagnosis and the number
      of days taken to develop pressure ulcers (c2=3.76, p=0.05). This study concluded
      that: the incidence rate was 13.84%; spinal cord injury was the clinical
      condition most likely to be associated with pressure ulcer development; and
      pressure ulcers occurred most frequently on the sacrum.

PMID- 22875377
TI  - Intersection of outcomes, ethics, and economics in critical care.

PMID- 22875378
TI  - The burdens of survivorship: an approach to thinking about long-term outcomes
      after critical illness.
AB  - Internationally accepted approaches to the study of functioning and disability
      can inform critical care practitioners and scholars in their study of functional
      limitations, disability, and quality of life after critical illness and intensive
      care. Therefore this article provides an introduction to the World Health
      Organization's International Classification of Functioning, Disability and Health
      (ICF). The Institute of Medicine has also recommended this approach for the study
      of disability. This conceptual framework divides potential problems as follows:
      problems in body structure and tissue, limitations in activity (i.e., functional
      limitations as assessed in standardized environments), and restrictions in
      participation (i.e., the inability to fulfill a social role). The ICF draws
      attention to effect modifiers that can prevent problems at one level from
      progressing (or conversely can hasten their progression) to profound decrements
      in a patient's quality of life. It is particularly relevant for studies of long
      term outcomes after critical illness and post-intensive care syndrome (PICS).
      This article provides a discussion of the ICF specific to the intensive care unit
      and the disablement process, with particular attention to new opportunities for
      intervention and their implications for cost and quality of life.

PMID- 22875379
TI  - Medical and economic implications of physical disability of survivorship.
AB  - Interventions developed in the last decade have led to impressive rates of
      survival from extreme critical illness. However, surviving an episode of critical
      illness is just the beginning. Discharge from the intensive care unit (ICU) is
      often the start of a long and challenging rehabilitation, mood disorders,
      cognitive impairment, financial hardship, and caregiver burden, burnout, and
      psychological distress. It has become increasingly apparent that the majority of
      patients who survive an episode of critical illness will have some degree of
      compromised physical function secondary to ICU Acquired Weakness (ICUAW) and a
      constellation of other physical disabilities. The spectrum of muscle, nerve, and
      brain dysfunction may be permanent and can significantly change the disposition
      for those who were previously independent. Furthermore, it may impose a
      substantial health care cost burden and compromise the reserve of even the most
      resilient family members. Important limitations in the current literature relate
      to our poor understanding of how to risk stratify, how to systematically educate
      and inform our patients and family caregivers about physical morbidity and
      complex patient care in the community, and how to develop, test, and implement
      rehabilitation programs tailored to individual need.

PMID- 22875380
TI  - Medical and economic implications of cognitive and psychiatric disability of
      survivorship.
AB  - Current research indicates that the majority of survivors of critical illness
      develop post-intensive care syndrome (PICS), which includes new or worsening
      cognitive or psychiatric disorders that persist for months to years after
      critical illness. These cognitive impairments and psychiatric disorders are
      profound and long-lasting, adversely affecting survivors' daily functioning,
      ability to return to work, and quality of life, as well as altering the lives of
      their family members. The medical effects of cognitive and psychiatric disability
      after critical illness translate directly into a large economic burden. A large
      and growing body of intensive care unit (ICU) survivors with cognitive and
      psychiatric morbidities presents challenges for research and identification of
      best practices and interventions, both during and after the ICU, including
      rehabilitation to prevent or remediate long-term neurological outcomes.

PMID- 22875381
TI  - Medical and economic implications of prolonged mechanical ventilation and
      expedited post-acute care.
AB  - This article describes the increasingly common phenomenon of prolonged mechanical
      ventilation in the context of the transition between the acute care hospital and
      post-acute care. Prolonged mechanical ventilation or chronic critical illness is
      associated with hospital mortality in the range of 20 to 40%, with median
      hospital length of stay ranging from 14 to 60 days. Fewer than 10% of patients
      are discharged home, and most hospital survivors require institutionalized post
      acute care in the form of long-term acute care, skilled nursing facilities, or
      inpatient rehabilitation. Acute hospital readmission is common. Because of
      prolonged functional disabilities and multiple underlying comorbid conditions,
      overall 1 year mortality for prolonged mechanical ventilation patients ranges
      from 50 to 60%. Survivors experience significant functional limitations. The
      prolonged institutional care and poor long-term outcomes of these patients bring
      into question the cost-effectiveness of prolonged mechanical ventilation after
      acute illness, especially for patients with poor long-term prognoses. New
      measures to facilitate assessments of long-term prognosis and improve
      communication with surrogate decision makers may reduce the amount of ineffective
      care for some patients requiring prolonged mechanical ventilation.

PMID- 22875382
TI  - Economics at the end of life: hospital and ICU perspectives.
AB  - Not all feasible care is desirable care. At the end of life, aggressive
      interventions may not only be futile but also inappropriate because they may
      impair the quality of the remaining life for both the patient and the caregiver.
      Although it is challenging to identify patients with a poor prognosis, certain
      terminal conditions among the elderly, such as end-stage dementia, heart failure,
      and metastatic cancer, demand a more measured use of aggressive care. Frank
      discussions with patients and family about their desires in the context of the
      prognosis, as well as symptom support, can yield both economic savings and better
      quality of life.

PMID- 22875383
TI  - System-level quality improvement initiatives: lessons from Keystone and other
      large-scale projects.
AB  - Health care systems around the world are seeking system-level interventions to
      improve the quality and safety of care because of increasing awareness that many
      patients do not receive recommended therapies or suffer preventable
      complications. This has also been motivated by a drive to deliver health care
      more cost-effectively, and to be more accountable to payers and other
      stakeholders. The Keystone Project in Michigan is one example of a large-scale
      system-level initiative that successfully changed the "culture of safety" in the
      intensive care units of participating hospitals and led to improvements in both
      process outcomes and clinical outcomes. This article discusses factors that
      contributed to the success of the Keystone Project and also considers its
      economic implications. There are also recommendations for the design and
      evaluation of future system-level quality improvement programs.

PMID- 22875384
TI  - Quality improvement in end-of-life critical care.
AB  - Patients, clinicians and policy makers are increasingly interested in measuring
      and improving the quality of health care at the end of life. The intensive care
      unit (ICU) is characterized by high mortality and frequent use of life-sustaining
      treatments, making critical care a natural target for these efforts. Indeed,
      multiple local and regional quality improvement efforts now specifically target
      the dying experience for ICU patients, patients at risk for ICU admission, and
      their families. These activities either target ICU caregivers through educational
      programs and quality incentives, or target patients and their families directly
      through palliative care and efforts to improve decisions around the end of life.
      Although these initiatives hold great promise, they also face inherent challenges
      it is difficult to measure the quality of end-of-life care, we lack practical
      targets for affecting quality, and uncertain political climates can often
      preclude serious discussions about end-of-life care. Moreover, these programs may
      lead to unintended consequences, potentially negatively impacting the very care
      they seek to improve. Future innovations surrounding how we measure the quality
      of end-of-life care and paradigm shifts in the way we think about ICU quality may
      help us to fully realize the goal of improving the dying process for ICU
      patients.

PMID- 22875385
TI  - The ethical and economic impact of defaults.
AB  - Medical care offered to the critically ill often occurs by default, unfolding
      automatically unless concerted effort is made to do otherwise. In their scope,
      defaults include traditional approaches to treatment and decision making, as well
      as policies deliberately set to promote specific health outcomes. Defaults are
      ethically sound to the extent that they foster patient well-being and autonomy.
      Unfortunately in practice, some defaults lead to ineffective, unwanted, and
      expensive care. This article reviews the ethical and economic impact of defaults,
      paying special attention to their influence on the practice of cardiopulmonary
      resuscitation and admission to the intensive care unit.

PMID- 22875386
TI  - Shaping end-of-life care: behavioral economics and advance directives.
AB  - A central but unmet challenge in health care delivery is to increase the
      probability that the care patients receive near the end of their life is
      consistent with their goals, values, and preferences. Providing patient-centered
      care at the end of life is challenging. In their final days, nearly a third of
      older Americans need critical decisions made regarding the use or nonuse of life
      sustaining interventions, but the patients themselves cannot participate in those
      decisions. Although this observation highlights the promise of advance directives
      (ADs), to date ADs have not delivered on this promise. This article provides a
      new framework, based in behavioral economic theory, that may explain the current
      failures of ADs and point to potential solutions. Specifically, it discusses how
      five well-described cognitive biases that pervade human decision making
      (affective forecasting errors, optimism bias, present-biased preferences,
      focusing effects, and default options) may account for deficiencies in the
      uptake, efficacy, and patient-centeredness of ADs. The text suggests potential
      solutions in need of evaluation, discusses metrics for assessing these
      interventions' benefits, and considers alternatives to the approaches advocated.

PMID- 22875387
TI  - Intensivist time allocation: economic and ethical issues surrounding how
      intensivists use their time.
AB  - Intensivists' time is a fundamentally constrained resource. Many factors can put
      intensivists under conditions in which demands for their time outstrip the amount
      of time available. The importance of intensivist time strain is increasing both
      because demand for intensivists exceeds supply and because the roles that
      intensivists are being asked to take on are constantly expanding. There is strong
      evidence that time strain affects the decisions that intensivists make; evidence
      about whether it impacts patient outcomes is mixed. In deciding how to allocate
      their time, intensivists face many challenges. This article highlights two of
      these challenges: (1) How should intensivists approach two common scheduling
      related issues (24/7 intensive care unit coverage and long blocks of service time
      that promote continuity but sacrifice weekends off) and balance these issues with
      the very real workforce concern of accelerated professional burnout? (2) What are
      the hidden financial impacts of intensivist participation in quality improvement
      programs, given current reimbursement systems?

PMID- 22875388
TI  - Cost-effective critical care: cost containment and rationing.
AB  - Rationing occurs whenever the demand for a good or service exceeds its supply.
      Therefore rationing is an inevitable occurrence in medicine and in critical care
      where the potential demand for effective medical care will exceed supply.
      Although there are many strategies to allocate medical resources one that is
      often considered is based on cost-effectiveness. Cost-effectiveness analysis
      attempts to estimate the value of individual medical treatments in terms of
      dollars and outcomes. Allocation of medical treatments based on cost
      effectiveness analysis requires valid estimates of both the costs and the
      effectiveness of treatments as well as some overarching body with the authority
      to enforce allocation based on these analyses. Limitations of allocation based on
      cost-effectiveness analysis in critical care include difficulties in estimating
      marginal costs of critical care treatments, limited evidence for any treatments
      with efficacy, and the ethical principle of rescuing identifiable lives in
      imminent risk of death. The prospect of a pandemic influenza-like infection has
      stimulated a lot of interest in hypothetical rationing strategies for the
      intensive care unit, none of which has been tested in actual pandemic scenarios.
      Given the burden of critical illness and the wide variation in resources a global
      approach to rationing is untenable. The article concludes with a vision of the
      future of allocation in critical care.

PMID- 22875389
TI  - The physician as rationer: uncertainty about the physician's role obligations.
AB  - Although the need to ration health care is increasingly accepted, the need for
      bedside physicians to participate in it is not. There are three common
      perspectives on physicians' roles in rationing: one is that bedside physicians
      should advocate fully for their patients and eschew rationing; another is that
      some rationing is permissible but should be imposed from outside the patient
      physician relationship; the third is that bedside physicians should
      simultaneously advocate for their individual patients and make bedside rationing
      decisions that incorporate societal interests. The first two conceptualizations
      are at odds with empirical evidence that physicians do ration at the bedside and
      the idea that doing so may be a necessary part of efforts to control costs,
      whereas the third raises difficult ethical questions about the extent of
      physicians' obligations to advocate maximally for their individual patients.

PMID- 22875390
TI  - The brave new world revealed: wrestling with reality, rationing, and rationality.
AB  - When Dr. Joseph Lynch, editor of Seminars in Respiratory and Critical Care
      Medicine, invited us to organize and edit this topic we-and our contributors-were
      initially baffled about how we could marry outcomes, ethics, and economics. His
      perspective as an elder-statesman, who has observed the evolution of critical
      care medicine over 4 decades, provided perspective as to how these three areas
      are intimately related and that their synthesis is essential if the US medical
      system is to best serve our populace as resources become increasingly limited.

PMID- 22875391
TI  - Health-related quality of life of long-term survivors of intensive care: changes
      after intensive care treatment. Experience of an Austrian intensive care unit.
AB  - OBJECTIVE: The aim of the study was to determine if health-related quality of
      life of long-term survivors changes 24 months after intensive care treatment
      compared to the quality of life before admission. METHODS: From 281 patients
      treated at the ICU in 2001, 132 survivors were contacted by phone on average 24
      months after discharge. Fernandez questionnaire was used to assess preadmission
      quality of life prospectively and postdischarge quality of life, retrospectively.
      In addition, age, sex, admission diagnosis, ICU length of stay, presence of organ
      failure, and necessity of mechanical ventilation were determined. RESULTS: In the
      101 ICU survivors who responded to the questionnaire, the total score of quality
      of life did not change significantly over time (5.48 +/- 5.3 before admission vs.
      5.6 +/- 5.8 at follow-up; p = 0.9). Similarly, the performance of normal daily
      activities did not alter (3.0 +/- 3.5 vs. 3.39 +/- 3.6; p = 0,3). In contrast,
      the ability to perform basic physiological activities worsened significantly
      (0.39 +/- 0.76 vs. 0.76 +/- 1.52; p = 0.037), whereas the emotional state
      improved significantly after intensive care treatment (2.08 +/- 1.78 vs. 1.46 +/-
      1.56, p = 0.003). In a stepwise multiple regression analysis the total score of
      quality of life before admission was the only variable which influenced the
      quality of life 2 years after ICU-stay. CONCLUSIONS: In the interviewed
      population the total score of health-related quality of life did not change after
      intensive care treatment. Surprisingly, emotional state improved significantly
      although physical performance decreased. Quality of life after ICU discharge was
      predominantly influenced by preadmission quality of life. However, these results
      are not reflective of all ICU survivors.

PMID- 22875392
TI  - Sleep apnea and pregnancy. An association worthy of study.

PMID- 22875393
TI  - Molecular and functional characterization of macrophage migration inhibitory
      factor (MIF) homolog of human from lymphatic filarial parasite Wuchereria
      bancrofti.
AB  - The ability of nematode parasites to survive in a highly complex immune system
      involves diverse strategies including production of a variety of host immune
      modulators. Various parasite-associated surface antigens or excretory and
      secretory products may possibly play a role in the host-parasite interactions and
      successful survival of parasite in their respective host. One among these
      molecules is a human cytokine homolog, macrophage migration inhibitory factor-1
      (MIF-1) in various parasites. We identified a homolog of this cytokine from human
      lymphatic filarial parasite, Wuchereria bancrofti, expression cloned and
      investigated its molecular characteristics and catalytic properties. We also
      assessed the humoral reactivity of the recombinant MIF-1 of W. bancrofti (rWb-MIF
      1) against sera belonging to different categories of individuals viz.
      microfilaremic, chronic patients, endemic normal, and non-endemic normal. Our
      results showed that the complete coding sequence of W. bancrofti is 1,078 bp,
      comprising two introns and three exons: first and second introns being 577 and
      153 bp long, while the three exons I, II, and III being 108, 173, and 67 bp long,
      respectively. The rWb-MIF-1 was overexpressed in a salt-inducible host,
      Escherichia coli GJ 1158, and its functional activity was determined by
      dopachrome tautomerase and insulin reduction assays. The results of both the
      assays showed that the purified protein is functionally active and hence folded
      appropriately. The rWb-MIF-1 protein did not show elevation of specific IgG4
      antibodies in microfilaremic cases, a hallmark in case of lymphatic filariasis,
      while it showed IgE reactivity in some of these cases (five out of ten).

PMID- 22875394
TI  - Patterns in avian malaria at founder and source populations of an endemic New
      Zealand passerine.
AB  - Significant progress in our understanding of disease transmission in the wild can
      be made by examining variation in host-parasite-vector interactions after founder
      events of the host. This study is the first to document patterns in avian
      malaria, Plasmodium spp., infecting an endemic New Zealand passerine, Anthornis
      melanura, at multiple-host subpopulations simultaneously. We assess the Beaudoin
      hypothesis of bimodal seasonality and use AIC model selection to determine host
      factors associated with disease prevalence. We had the rare opportunity to test
      the enemy release hypothesis (ERH) after a recent colonisation event of the
      bellbird host. Four Plasmodium species were found to infect bellbirds. Temporal
      patterns of three exotic parasite lineages, including GRW06 Plasmodium (Huffia)
      elongatum, SYAT05 Plasmodium (Novyella) vaughani and a Plasmodium (Haemamoeba)
      relictum, were sporadic with low prevalence year round. The fourth species was an
      endemic parasite, an unresolved Plasmodium (Novyella) sp. here called ANME01,
      which exhibited a strong winter peak at the source subpopulations possibly
      indicating greater immune stressors at the densely populated source site. At the
      colonies, we observed bimodal seasonality in the prevalence of ANME01 with autumn
      and spring peaks. These infection peaks were male-biased, and the amplitude of
      sex bias was more pronounced at the newer colony perhaps due to increased
      seasonal competition resulting from territory instability. We observed a decrease
      in parasite species diversity and increase in body condition from source to
      founder sites, but statistical differences in the direct relationship between
      body condition and malaria prevalence between source and colony were weak and
      significant only during winter. Though our data did not strongly support the ERH,
      we highlight the benefits of 'conspecific release' associated with decreased
      population density and food competition. Our findings contribute to the
      identification of ecological and environmental drivers of variability in malaria
      transmission, which is valuable for predicting the consequences of both natural
      range expansions, as well as host re-introductions resulting from intensive
      conservation practices.

PMID- 22875395
TI  - Anti-leishmanial and toxicity activities of some selected Iranian medicinal
      plants.
AB  - Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania.
      Cutaneous leishmaniasis is the most common form of leishmaniasis in Iran. As
      there is not any vaccine for leishmaniasis, treatment is important to prevent the
      spreading of parasites. There is, therefore, a need to develop newer drugs from
      different sources. The aim of this study was to assess anti-leishmanial activity
      of the ethanolic extracts of 17 different medicinal plants against Leishmania
      major promastigotes and macrophage cell line J774. The selection of the hereby
      studied 17 plants was based on the existing information on their local
      ethnobotanic history. Plants were dried, powdered, and macerated in a
      hydroalcoholic solution. Resulting extracts have been assessed for in vitro anti
      leishmanial and brine shrimp toxicity activities. Four plants, Caesalpinia
      gilliesii, Satureia hortensis, Carum copticum heirm, and Thymus migricus,
      displayed high anti-leishmanial activity (IC50, 9.76 +/- 1.27, 15.625 +/- 3.76,
      15.625 +/- 5.46, and 31.25 +/- 15.44 MUM, respectively) and were toxic against
      the J774 macrophage cell line at higher concentrations than those needed to
      inhibit the parasite cell growth (IC50, 45.13 +/- 3.17, 100.44 +/- 17.48, 43.76
      +/- 0.78, and 39.67 +/- 3.29 MUM, respectively). Glucantime as positive control
      inhibited the growth of L. major promastigotes with IC50 = 254 MUg/ml on
      promastigotes (1 * 10(6)/100 MU/well) of a log phase culture, without affecting
      the growth of J774 macrophages. These data revealed that C. gilliesii, S.
      hortensis, C. copticum heirm, and T. migricus extracts contain active compounds,
      which could serve as alternative agents in the control of cutaneous
      leishmaniasis. The activity of these herbs against L. major promastigotes and
      macrophage cell line J774 was reported for the first time in our study.

PMID- 22875396
TI  - Management of the patient with neutropenic sepsis.

PMID- 22875397
TI  - How to survive as a medical registrar.

PMID- 22875398
TI  - Using infection specialists.

PMID- 22875399
TI  - Carotid blowout.

PMID- 22875400
TI  - Microbial D-xylonate production.
AB  - D-Xylonic acid is a versatile platform chemical with reported applications as
      complexing agent or chelator, in dispersal of concrete, and as a precursor for
      compounds such as co-polyamides, polyesters, hydrogels and 1,2,4-butanetriol.
      With increasing glucose prices, D-xylonic acid may provide a cheap, non-food
      derived alternative for gluconic acid, which is widely used (about 80 kton/year)
      in pharmaceuticals, food products, solvents, adhesives, dyes, paints and
      polishes. Large-scale production has not been developed, reflecting the current
      limited market for D-xylonate. D-Xylonic acid occurs naturally, being formed in
      the first step of oxidative metabolism of D-xylose by some archaea and bacteria
      via the action of D-xylose or D-glucose dehydrogenases. High extracellular
      concentrations of D-xylonate have been reported for various bacteria, in
      particular Gluconobacter oxydans and Pseudomonas putida. High yields of D
      xylonate from D-xylose make G. oxydans an attractive choice for biotechnical
      production. G. oxydans is able to produce D-xylonate directly from plant biomass
      hydrolysates, but rates and yields are reduced because of sensitivity to
      hydrolysate inhibitors. Recently, D-xylonate has been produced by the genetically
      modified bacterium Escherichia coli and yeast Saccharomyces cerevisiae and
      Kluyveromyces lactis. Expression of NAD(+)-dependent D-xylose dehydrogenase of
      Caulobacter crescentus in either E. coli or in a robust, hydrolysate-tolerant,
      industrial Saccharomyces cerevisiae strain has resulted in D-xylonate titres,
      which are comparable to those seen with G. oxydans, at a volumetric rate
      approximately 30% of that observed with G. oxydans. With further development,
      genetically modified microbes may soon provide an alternative for production of D
      xylonate at industrial scale.

PMID- 22875401
TI  - Review of the specific effects of microwave radiation on bacterial cells.
AB  - The aim of the present review was to evaluate the literature suggesting that
      consideration be given to the existence of specific microwave (MW) effects on
      prokaryotic microorganisms; that is, effects on organisms that cannot be
      explained by virtue of temperature increases alone. This review considered a
      range of the reported effects on cellular components; including membranes,
      proteins, enzyme activity as well as cell death. It is concluded that the
      attribution of such effects to non-thermal mechanisms is not justified due to
      poor control protocols and because of the possibility that an unmeasurable
      thermal force, relating to instantaneous temperature (T (i)) that occurs during
      MW processing, has not been taken into account. However, due to this lack of
      control over T (i), it also follows that it cannot be concluded that these
      effects are not 'non-thermal'. Due to this ambiguity, it is proposed that
      internal 'micro'-thermal effects may occur that are specific to MW radiation,
      given its inherent unusual energy deposition patterning.

PMID- 22875403
TI  - From biomass wastes to large-area, high-quality, N-doped graphene: catalyst-free
      carbonization of chitosan coatings on arbitrary substrates.
AB  - Chitosan is a N-containing biopolymer that can form high-quality films on glass,
      quartz, metals and other hydrophilic surfaces. Pyrolysis of chitosan films under
      argon at 800  degrees C and under inert atmosphere gives rise to high-quality
      single layer N-doped graphene films (over 99% transmittance) as evidenced by XPS,
      Raman spectroscopy, and TEM imaging.

PMID- 22875402
TI  - Therapeutic application of injectable thermosensitive hydrogel in preventing
      local breast cancer recurrence and improving incision wound healing in a mouse
      model.
AB  - Many drug delivery systems (DDSs) have been investigated for local targeting of
      malignant disease with the intention of increasing anti-tumor activity and
      minimizing systemic toxicity. An injectable thermosensitive hydrogel was applied
      to prevent locoregional recurrence of 4T1 breast cancer in a mouse model. The
      presented hydrogel, which is based on poly(ethyleneglycol)-poly(epsilon
      caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), flows freely at normal
      temperature, forms a gel within seconds in situ at body temperature, and
      eventually releases the drug in a consistent and sustained fashion as it
      gradually biodegrades. Locoregional recurrence after primary tumor removal was
      significantly inhibited in mice treated with the paclitaxel (PTX)-loaded PECE
      hydrogel subcutaneously (9.1%) administered, compared with the blank hydrogel
      (80.0%), systemic (77.8%) and locally (75.0%) administered PTX, and the control
      group (100%) (P < 0.01). In addition, tensile strength measurements of the
      surgical incisions showed that the PECE hydrogel accelerates wound healing at
      postoperative day 7 (P < 0.05), and days 4 and 14 (P > 0.05), in agreement with
      histopathological examinations. This novel DDSs represents a promising approach
      for local adjuvant therapy in malignant disease.

PMID- 22875404
TI  - Kinetics and thermodynamics of 1-anilino-8-naphthalene sulfonate interactions
      with Urinary Trypsin Inhibitor.
AB  - The interactions between Urinary Trypsin Inhibitor (UTI) and 1-anilino-8
      naphthalene sulfonate (ANS) were investigated by fluorescence spectra, isothermal
      titration calorimetry and molecular modeling. The results revealed the presence
      of four specific binding sites for ANS on UTI, with interactions driven mainly by
      electrostatic forces. The four specific binding sites indicated the involvement
      of four hydrophobic patches on UTI. Experimental data also confirmed the presence
      of a further five nonspecific binding sites that interacted mainly by the
      formation of salt bridges between the sulfonates of ANS and positive residues on
      the surface of UTI.

PMID- 22875405
TI  - Midurethral sling incision: indications and outcomes.
AB  - INTRODUCTION AND HYPOTHESIS: Controversy continues over the effectiveness of
      sling incision, which is the most common operative approach to treating
      complications following suburethral sling insertion. This retrospective analysis
      assessed the indications for sling incision and patient outcomes regarding
      resolution of complications and stress urinary incontinence. METHODS: A review
      was conducted of the medical records of women who underwent sling incision
      between 2003 and 2010. Data such as surgical indications, ultrasound findings and
      medical outcomes were extracted from 198 records, and descriptive and inferential
      statistical methods of analysis were used. RESULTS: In the 198 patients eligible
      for study inclusion, the primary reasons for sling incision were overactive
      bladder (68 %), voiding dysfunction (61 %), and recurrent urinary tract
      infections (53 %). Additional complications included dyspareunia (18 %), chronic
      pelvic pain (17 %), and sling exposure (15 %). Sling incision led to immediate
      postoperative cure of voiding dysfunction in 97 % of patients. Cure rates for
      overactive bladder and dyspareunia were 60 % and 94 % respectively. Chronic
      pelvic pain was resolved in 82 % of cases and all cases of sling exposure were
      cured. Eighty-five (61 %) of the 140 patients who were continent before sling
      incision developed recurrent stress urinary incontinence (SUI) postoperatively.
      CONCLUSIONS: These findings indicate that sling incision can be highly successful
      in improving voiding dysfunction and dyspareunia, and moderately successful in
      curing overactive bladder and chronic pain. However, SUI may recur in more than
      60 % of the patients undergoing sling incision. Consequently, patients being
      considered for a sling incision procedure should be informed about this possible
      complication.

PMID- 22875406
TI  - Groin abscess due to a forgotten midurethral sling connector.
AB  - Midurethral slings (MUS) have been used for female stress urinary incontinence
      throughout the past decade on a worldwide scale. Although this minimally invasive
      treatment has high success rates, formation of groin abscesses, as well as
      vaginal and urethral erosions, can occur after the procedure. We report a patient
      presenting with groin abscess and sinus tract formation after a transobturator
      tape procedure. The patient exhibited a swollen sinus tract, which drained the
      abscess at the site of the tape entry to the obturator foramen within her inner
      left groin. She was referred to our department after unsuccessful medical and
      surgical treatments. Surgical exploration revealed a forgotten MUS connector
      located between the mesh and hook within the skin incision. To the best of our
      knowledge, this is the first report of such a case.

PMID- 22875407
TI  - Association between alcohol consumption in healthy midlife and telomere length in
      older men. The Helsinki Businessmen Study.
AB  - There are scarce data of alcohol consumption and telomere length, an indicator of
      biological age. In 1974, detailed alcohol consumption was available for a
      socioeconomically homogenous cohort of middle-aged men (The Helsinki Businessmen
      Study). Their alcohol use, divided into 5 groups (zero, 1-98, 99-196, 197-490,
      >490 g/week) has been repeatedly assessed until old age. In 2002/2003, leukocyte
      telomere length (LTL) and the proportion of short telomeres (less than 5
      kilobases) were measured in a random subcohort of 499 men (mean age 76 years)
      using the Southern blot. Age-adjusted mean LTL in the 5 midlife alcohol
      consumption groups were 8.33, 8.24, 8.12, 8.13, and 7.87 kilobases, respectively
      (P < 0.001). The respective proportions (%) for short telomeres were 11.24,
      11.52, 11.89, 12.08, and 13.47 (P = 0.004). The differences remained after
      further adjustments (ever smoking, body mass index, cholesterol, perceived
      fitness) for LTL (P = 0.03) and tended to remain for proportion of short
      telomeres (P = 0.07). Neither LTL, nor proportion of short telomeres, were
      associated with contemporary alcohol consumption groups in old age. Even minor
      alcohol consumption in midlife was significantly associated with shorter telomere
      length in old age. The differences represent an up to 10 year gap in biological
      age between zero and highest consumption.

PMID- 22875408
TI  - Eicosapentaenoic acid suppresses adverse effects of C-reactive protein
      overexpression on pressure overload-induced cardiac remodeling.
AB  - Serum C-reactive protein (CRP) elevation is associated with poor clinical outcome
      in patients with heart failure (HF). We previously reported that CRP exacerbates
      the development of pressure overload-induced cardiac remodeling through an
      enhanced inflammatory response and oxidative stress. In the present study, we
      examined the effect of eicosapentaenoic acid (EPA), a suppressor of inflammatory
      response and oxidative stress, on pressure overload-induced cardiac remodeling.
      Transverse aortic constriction (TAC) was performed on transgenic mice
      overexpressing CRP (CRPtg) and nontransgenic littermates (TAC/CON). CRPtg with
      TAC operation were randomly assigned to be fed a standard diet (TAC/CRPtg) or an
      EPA-enriched diet (7 % of total energy) (TAC/CRPtg/EPA). Myocardial mRNA level of
      transforming growth factor-beta1, proinflammatory cytokines, and oxidative stress
      markers were increased in TAC/CRPtg in comparison with TAC/CON 1 and 4 weeks
      after the operation. These parameters were significantly suppressed in
      TAC/CRPtg/EPA compared with TAC/CRPtg. In addition, after 4 weeks of EPA
      treatment, as compared with TAC/CRPtg, TAC/CRPtg/EPA mice demonstrated reduced
      heart and lung weights, increased left ventricular fractional shortening, and
      decreased left ventricular end-diastolic pressure, together with decreased
      cardiac hypertrophy, fibrosis, and improved cardiac function. In conclusion, the
      anti-inflammatory and antioxidative properties of EPA may make it an effective
      therapeutic strategy for adverse cardiac remodeling associated with CRP
      overexpression.

PMID- 22875409
TI  - Effects of the left ventricular assist device on the compliance and
      distensibility of the carotid artery.
AB  - We investigated the impact of continuous-flow left ventricular assist devices
      (LVAD) on the carotid elastic properties. Carotid artery parameters (diameter
      distensibility (DD), cross-sectional distensibility (CSD), diameter compliance
      (DC), cross-sectional compliance (CSC), and incremental elastic modulus (IEM))
      were measured in a cross-sectional study using a standard ultrasound with a 10
      MHz linear array probe. Measurements (mean +/- SEM) were made in separate groups
      at various clinical time points: prior to LVAD surgery (baseline; 13 male/3
      female; age 48 +/- 3 years), 1 week following LVAD placement (acute; 12 male/2
      female; age 47 +/- 3 years), approximately 24 weeks following LVAD surgery
      (chronic; 13 male/2 female; age 52 +/- 3 years), and in a group of healthy
      subjects (controls; 9 male/1 female; age 51 +/- 4 years). Distensibility
      properties were lower (P < 0.05) in the acute (DD 2.3 % +/- 0.4 %; CSD 4.7 % +/-
      0.8 %) and chronic (DD 2.2 % +/- 0.4 %; CSD 4.5 +/- 0.9 %) compared with the
      baseline (DD 5.9 % +/- 0.7 %; CSD 12.2 % +/- 1.5 %) and control (DD 5.8 % +/- 0.6
      %; CSD 11.9 % +/- 1.3 %) groups. Compliance properties were lower (P < 0.05) in
      the chronic (DC 4.4 +/- 0.7 mm/mmHg * 10(-3); CSC 1.2 +/- 0.2 mmHg(-1) * 10(-3))
      compared with acute (DC 9.0 +/- 1.6 mm/mmHg * 10(-3); CSC 2.6 +/- 0.4 mmHg(-1) *
      10(-3)) and baseline (DC 11.1 +/- 1.1 mm/mmHg * 10(-3); CSC 3.3 +/- 0.4 mmHg(-1)
      * 10(-3)) groups. The compliance properties in the control (DC 8.3 +/- 0.8
      mm/mmHg * 10(-3); CSC 2.4 +/- 0.2 mmHg(-1) * 10(-3)) group were not different
      from any of the patient groups. The IEM was higher (P < 0.05) in the chronic
      (6908 +/- 1269 mmHg) compared with acute (2739 +/- 412 mmHg), baseline (1849 +/-
      177 mmHg), and control (2349 +/- 241 mmHg) groups. Chronic continuous-flow LVAD
      support is associated with lower carotid artery compliance and distensibility,
      which may place further strain on the left ventricle.

PMID- 22875410
TI  - Local and global effects of motivation on cognitive control.
AB  - Motivation has been found to enhance cognitive control, but the mechanisms by
      which this occurs are still poorly understood. Cued motivational incentives
      (e.g., monetary rewards) can modulate cognitive processing locally-that is, on a
      trial-by-trial basis (incentive cue effect). Recently, motivational incentives
      have also been found to produce more global and tonic changes in performance, as
      evidenced by performance benefits on nonincentive trials occurring within
      incentive blocks (incentive context effect). In two experiments involving
      incentivized cued task switching, we provide systematic evidence that the two
      effects are dissociable. Through behavioral, diffusion-modeling, and individual
      differences analyses, we found dissociations between local and global
      motivational effects that were linked to specific properties of the incentive
      signals (i.e., timing), while also ruling out alternative interpretations (e.g.,
      practice and speed-accuracy trade-off effects). These results provide important
      clues regarding the neural mechanisms by which motivation exerts both global and
      local influences on cognitive control.

PMID- 22875411
TI  - Splenic artery embolization: a single center experience on the safety, efficacy,
      and clinical outcomes.
AB  - PURPOSE: We aimed to assess the safety, efficacy, and clinical outcomes of
      splenic artery embolization (SAE). MATERIALS AND METHODS: A total of 50 patients
      (male:female, 33:17; mean age, 49 years) who underwent 50 SAEs between 1998 and
      2011 were retrospectively studied. The procedure indications included aneurysm or
      pseudoaneurysm (n=15), gastric variceal hemorrhage (n=15), preoperative reduction
      of surgical blood loss (n=9), or other (n=11). In total, 22 procedures were
      elective, and 28 procedures were urgent or emergent. The embolic agents included
      coils (n=50), gelatin sponges (n=15), and particles (n=4). The measured outcomes
      were the technical success of the procedure, efficacy, side effects, and the 30
      day morbidity and mortality rates. RESULTS: All embolizations were technically
      successful. The procedure efficacy was 90%; five patients (10%) had a recurrent
      hemorrhage requiring a secondary intervention. Side effects included hydrothorax
      (n=26, 52%), thrombocytosis (n=16, 32%), thrombocytopenia (n=13, 26%), and
      postembolization syndrome (n=11, 22%). Splenic infarcts occurred in 13 patients
      (26%). The overall and procedure-specific 30-day morbidity rates were 38% (19/50)
      and 14% (splenoportal thrombosis, 3/50; encapsulated bacterial infection, 1/50;
      splenic abscess, 1/50; femoral hematoma requiring surgery, 1/50; hydrothorax
      requiring drainage, 1/50). The overall and procedure-specific 30-day mortality
      rates were 8% (4/50) and 0%. The multivariate analysis showed that advanced
      patient age (P = 0.037), postprocedure thrombocytopenia (P = 0.008),
      postprocedure hydrothorax (P = 0.009), and the need for a secondary intervention
      (P = 0.004) predicted the 30-day morbidity, while renal insufficiency (P <
      0.0001), preprocedure hemodynamic instability (P = 0.044), and preprocedure
      leukocytosis (P < 0.0001) were prognostic factors for the 30-day mortality.
      CONCLUSION: SAE was performed with high technical success and efficacy, but the
      outcomes showed nontrivial morbidity rates. Elderly patients with
      thrombocytopenia and hydrothorax after SAE, and patients who require secondary
      interventions, should be monitored for complications.

PMID- 22875412
TI  - Extended heart failure clinic follow-up in low-risk patients: a randomized
      clinical trial (NorthStar).
AB  - BACKGROUND: Outpatient follow-up in specialized heart failure clinics (HFCs) is
      recommended by current guidelines and implemented in most European countries, but
      the optimal duration of HFC programmes has not been established. Nor is it known
      whether all or only high-risk patients, e.g. identified by NT-proBNP, might
      benefit from an extended HFC follow-up. METHODS AND RESULTS: In a multi-centre
      setting, we randomly assigned 921 clinically stable systolic heart failure (HF)
      outpatients on optimal medical therapy to undergo either an extended follow-up in
      the HFC (n = 461) or referral back to their general practitioner (GP) (n = 460).
      The primary composite endpoint was death or a cardiovascular admission. Secondary
      endpoints included mortality, an HF admission, quality of life, number of days
      admitted, and number of admissions. The median age of the patients was 69 years;
      23% were females; the median left ventricular ejection fraction was 0.30; and the
      median NT-proBNP was 801 pg/mL; 89% were in NYHA class I-II. The median follow-up
      was 2.5 years. Time-to-event did not differ between groups (HFC vs. GP) (HR:
      1.17, 95% CI: 0.95-1.45, P = 0.149). The two groups did not differ with respect
      to any of the secondary endpoints at the follow-up (P> 0.05 for all). In high
      risk patients identified by NT-proBNP >=1000 pg/mL, no benefit from HFC follow-up
      was found (P = 0.721). CONCLUSION: Irrespective of the level of NT-proBNP stable
      HF patients on optimal medical therapy do not benefit from long-term follow-up in
      a specialized HFC in a publicly funded universal access healthcare system. Heart
      failure patients on optimal medical therapy with mild or moderate symptoms are
      safely managed by their personal GP. TRIAL REGISTRATION: www.Centerwatch.com:
      173491 (NorthStar).

PMID- 22875413
TI  - A systematic review of the effect of low-level laser therapy in the management of
      breast cancer-related lymphedema.
AB  - PURPOSE: The purpose of this study was to review the effect of low-level laser
      therapy (LLLT) in the management of breast cancer-related lymphedema (BCRL).
      METHODS: A systematic review of seven databases for clinical trials for LLLT in
      the management of BCRL published between 1990 and 2011 was performed. RESULTS: A
      total of eight studies on 230 patients were found. The methodological qualities
      of the selected studies were assessed with the Physiotherapy Evidence Database
      scale, and the studies were categorized according to Sackett's levels of
      evidence. Five studies were graded at evidence level II. Two studies were graded
      at evidence level III, and the remaining study was graded at evidence level V.
      CONCLUSIONS: There is moderate to strong evidence for the effectiveness of LLLT
      for the management of BCRL from five small studies of acceptable methodological
      quality. A dose of 1-2 J/cm(2) per point applied to several points covering the
      fibrotic area can reduce limb volume following BCRL. Further well-designed, large
      scale studies are required to determine more precisely how effective LLLT may be
      in BCRL.

PMID- 22875414
TI  - Ovarian cancer surgery: health and coping during the perioperative period.
AB  - PURPOSE: The study objective was to survey general health and coping in women
      undergoing ovarian cancer surgery, and subsequently to develop and test a
      supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on
      the suspicion of ovarian cancer participated in a follow-up questionnaire study
      in which the Short Form-36 Questionnaire was used to survey general health twice
      during the perioperative period and the Life Orientation Questionnaire (SOC) was
      used once to define the postoperative coping capacity. An evidence-based,
      preoperative supportive care programme was subsequently developed and tested.
      This consisted of lean methodology applied to clinical pathways, preoperative
      optimisation, and psychosocial care and support. RESULTS: From 294 women
      allocated to three study groups, a total of 546 Short Form-36 questionnaires and
      253 SOC questionnaires were available for analysis. The overall response rate was
      86 %. The presence of ascites, a pelvic mass, and a Risk of Malignancy Index >200
      proved to be appropriate clinical markers for intensified preoperative care.
      Concerning physical health, levels were low throughout the perioperative period;
      the majority however stayed within standard levels. Concerning mental health,
      levels were below standard during the entire period, but did improve with time,
      also in women in whom the potential cancer diagnosis was refuted. The
      preoperative differences between these groups leveled out postoperatively in
      terms of physical health. At the end of the perioperative period, the coping
      capacity was close to normal. CONCLUSIONS: A need for supportive care during the
      perioperative period was identified. This should be adjusted to the nature of the
      disease and the extent of the treatment. Participation in a preoperative
      supportive programme supported physical health during the perioperative period;
      however, further support of mental health seemed required.

PMID- 22875415
TI  - High incidence of bloodstream infection detected by surveillance blood cultures
      in hematology patients on corticosteroid therapy.
AB  - PURPOSE: The aim of our study was to evaluate the frequency of "occult"
      bacteremia/fungemia as well as the diversity of pathogens involved in hematology
      patients treated with corticosteroids. METHODS: Daily surveillance blood cultures
      were taken from patients treated with corticosteroids as part of their intensive
      chemotherapy or during graft-versus-host disease following hematopoietic stem
      cell transplantation during a 3-year period (2006-2009). We reviewed the
      frequency of occult bacteremia/fungemia as well as the pathogens involved.
      RESULTS: During the 3-year period, 3,821 bottles were cultured from 215 patients
      and 4.9 % of the bottles tested were positive. Surveillance blood cultures
      revealed bloodstream infection in 24 % of the patients (definite bloodstream
      infection in 16 %). Seventy-five percent of patients were still afebrile when
      microorganisms were detected. The main risk group was acute lymphocytic leukemia
      patients undergoing remission induction chemotherapy. The pathogens cultured most
      frequently were coagulase-negative staphylococci, enterococci, Escherichia coli,
      and Pseudomonas aeruginosa. CONCLUSIONS: A high incidence of occult bacteremia
      was detected by surveillance blood cultures. Further studies are needed to
      evaluate if a strategy based on surveillance blood cultures can reduce mortality
      related to bloodstream infections.

PMID- 22875416
TI  - Taste and smell function in pediatric blood and marrow transplant patients.
AB  - BACKGROUND: The intensive conditioning regimens of a pediatric blood and marrow
      transplant (BMT) can limit voluntary intake leading to a risk of malnutrition.
      Poor dietary intake is likely multi-factorial with a change in taste and smell
      function potentially being one contributing factor limiting intake, though this
      is not well studied. This research aimed to assess the taste and smell function
      of a cohort of pediatric BMT patients. METHODS: A total of ten pediatric BMT
      patients (8-15 years) were recruited to this study. Smell function was assessed
      using a three-choice 16-item odour identification test. Taste function was
      assessed using five concentrations of sweet, sour, salty and bitter tastants. All
      tests were completed at admission to transplant and monthly until taste and smell
      function had normalised. RESULTS: At the 1-month post-transplant assessment, one
      third of participants displayed some evidence of taste dysfunction and one third
      smell dysfunction, but there was no evidence of dysfunction in any patient at the
      2-month assessment. CONCLUSION: Contrary to reports of long-term loss of taste
      and smell function in adults, dysfunction early in transplant was found to be
      transient and be resolved within 2 months post-transplant in children. Further
      research is required to determine the causes of poor dietary intake in this
      population.

PMID- 22875417
TI  - International Conference on Chemistry and the Environment in Zurich.

PMID- 22875419
TI  - Influence of pH and ozone dose on the content and structure of haloacetic acid
      precursors in groundwater.
AB  - This study investigated the effects of pH (6-10) and ozone dose [0.4-3.0 mg
      O(3)/mg dissolved organic carbon (DOC)] on the content and structure of
      haloacetic acid (HAA) precursors in groundwater rich in natural organic matter
      (NOM; DOC 9.85 +/- 0.18 mg/L) during drinking water treatment. The raw water was
      ozonated in a 2 L glass column. NOM fractionation was carried out using XAD
      resins. HAA formation potential (HAAFP) was determined according to standard EPA
      Method 552. NOM characterization revealed it is mostly hydrophobic (65 % fulvic
      and 14 % humic acids). Hydrophobic NOM significantly influences HAA formation, as
      confirmed by the high HAAFP (309 +/- 15 MUg/L). Ozonation at pH 6-10 led to
      changes in NOM structure, i.e. complete humic acid oxidation, and increased the
      hydrophilic NOM fraction content (65-90 % achieved using 3.0 mg O(3)/mg DOC). The
      highest degree of NOM oxidation and HAA precursor removal was achieved at pH 10
      (up to 68 % HAAFP). Ozonation pH influenced the distribution of HAA precursor
      content, as increasing the pH from 6 to 10 increased the reactivity of the
      hydrophilic fraction, with the HAAFP increasing from 19.1 +/- 6.0 MUg/mg DOC in
      raw water to 152 +/- 8 MUg/mg DOC in ozonated water. The degree of HAA precursor
      removal depends on the dominant oxidation mechanism, which is related to the
      applied ozone dose and the pH of the oxidation process. Ozonation at pH 10
      favours the mechanism of radical NOM oxidation and was the most effective for
      HAAFP reduction, with the efficacy of the process improving with increasing ozone
      dose.

PMID- 22875418
TI  - Transformation and biodegradation of 1,2,3-trichloropropane (TCP).
AB  - PURPOSE: 1,2,3-Trichloropropane (TCP) is a persistent groundwater pollutant and a
      suspected human carcinogen. It is also is an industrial chemical waste that has
      been formed in large amounts during epichlorohydrin manufacture. In view of the
      spread of TCP via groundwater and its toxicity, there is a need for cheap and
      efficient technologies for the cleanup of TCP-contaminated sites. In situ or on
      site bioremediation of TCP is an option if biodegradation can be achieved and
      stimulated. This paper presents an overview of methods for the remediation of TCP
      contaminated water with an emphasis on the possibilities of biodegradation.
      CONCLUSIONS: Although TCP is a xenobiotic chlorinated compound of high chemical
      stability, a number of abiotic and biotic conversions have been demonstrated,
      including abiotic oxidative conversion in the presence of a strong oxidant and
      reductive conversion by zero-valent zinc. Biotransformations that have been
      observed include reductive dechlorination, monooxygenase-mediated cometabolism,
      and enzymatic hydrolysis. No natural organisms are known that can use TCP as a
      carbon source for growth under aerobic conditions, but anaerobically TCP may
      serve as electron acceptor. The application of biodegradation is hindered by low
      degradation rates and incomplete mineralization. Protein engineering and genetic
      modification can be used to obtain microorganisms with enhanced TCP degradation
      potential.

PMID- 22875420
TI  - Sorption of tetracyclines onto natural soils: data analysis and prediction.
AB  - Residues of tetracyclines reach soils as a result of animal waste application.
      Sorption is a key process in transport, fate, and effects of contaminants in the
      environment. In this work, we have attempted to predict the sorption of four
      widely used tetracyclines (oxytetracycline, tetracycline, chlortetracycline, and
      doxycycline) from soil physicochemical properties. Batch sorption experiments
      were performed on 15 natural soils with a broad range of physicochemical
      properties, and the data were fitted to several isotherm models. Multivariate
      analysis methods were conducted to identify the main factors affecting the
      sorption distribution coefficients (K (d)) of the tetracyclines at two aqueous
      concentration levels (100 and 400 MUg L(-1)). All four tetracycline sorption
      isotherms in alkaline and acidic soils were well described by the Freundlich and
      Langmuir equation, respectively. At intermediate soil pH (from 5.3 to 7),
      oxytetracycline and tetracycline exhibited Freundlich behavior, whereas
      chlortetracycline and doxycycline followed a Langmuir model. Two partial least
      squares (PLS) models were developed. The first one uses five soil descriptors as
      input variables; the second uses, pH, cation exchange capacity (CEC), and log K
      (d,OTC). Both models satisfactorily predicted distribution coefficients within a
      factor of 1.5. Sorption of tetracyclines in soil is governed by several factors,
      in the following order of importance: solution speciation, CEC (dominant at
      acidic-neutral soil pH), transition metal content, and texture. The PLS models
      indicated that tetracycline sorption can be predicted using a minimal set of soil
      descriptors including oxytetracycline sorption data.

PMID- 22875421
TI  - Geographical distribution of non-PBDE-brominated flame retardants in mussels from
      Asian coastal waters.
AB  - Hexabromocyclododecanes (HBCDs), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE),
      and decabromodiphenyl ethane (DBDPE) used as alternatives for polybrominated
      diphenyl ethers (PBDEs) are also persistent in the environment as PBDEs. Limited
      information on these non-PBDE brominated flame retardants (BFRs) is available; in
      particular, there are only few publications on environmental pollution by these
      contaminants in the coastal waters of Asia. In this regard, we investigated the
      contamination status of HBCDs, BTBPE, and DBDPE in the coastal waters of Asia
      using mussels as a bioindicator. Concentrations of HBCDs, BTBPE, and DBDPE were
      determined in green (Perna viridis) and blue mussels (Mytilus edulis) collected
      from the coastal areas in Cambodia, China (mainland), SAR China (Hong Kong),
      India, Indonesia, Japan, Malaysia, the Philippines, and Vietnam on 2003-2008.
      BTBPE and DBDPE were analyzed using GC-MS, whereas HBCDs were determined by LC
      MS/MS. HBCDs, BTBPE, and DBDPE were found in mussels at levels ranging from <0.01
      to 1,400, <0.1 to 13, and <0.3 to 22 ng/g lipid wt, respectively. Among the three
      HBCD diastereoisomers, alpha-HBCD was the dominant isomer followed by gamma- and
      beta-HBCDs. Concentrations of HBCDs and DBDPE in mussels from Japan and Korea
      were higher compared to those from the other Asian countries, indicating
      extensive usage of these non-PBDE BFRs in Japan and Korea. Higher levels of HBCDs
      and DBDPE than PBDEs were detected in some mussel samples from Japan. The results
      suggest that environmental pollution by non-PBDE BFRs, especially HBCDs in Japan,
      is ubiquitous. This study provides baseline information on the contamination
      status of these non-PBDE BFRs in the coastal waters of Asia.

PMID- 22875422
TI  - Characterization and lead(II), cadmium(II), nickel(II) biosorption of dried
      marine brown macro algae Cystoseira barbata.
AB  - PURPOSE: The objectives of this research are to identify the functional groups
      and determine corresponding pK (a) values of the acidic sites on dried brown
      algae Cystoseira barbata using FTIR and potentiometric titrations, and to
      investigate the biosorption ability of biomass towards divalent nickel, cadmium,
      and lead ions. Adsorption was studied as a function of solution pH and contact
      time, and experimental data were evaluated by the Langmuir isotherm model.
      METHODS: CaCl(2) pretreatment was applied to the sorbent for enhancing the metal
      uptake capacity. The effect of solution pH on biosorption equilibrium was
      investigated in the pH range of 1.5-5.0. Individual as well as competitive
      adsorption capacity of the sorbent were studied for metal cations and mixtures.
      RESULTS: The retention of the tested metal ions was mostly influenced from pH in
      the range of 1.5-2.5, then stayed almost constant up to 5.0, while Ni(II) uptake
      showed the highest variation with pH. Potentiometric titrations were performed to
      find the number of strong and weak acidic groups and their acidity constants. The
      density of strong and weak acidic functional groups in the biomass were found to
      be 0.9 and 2.26 mmol/g, respectively. The FTIR spectra of the sorbent samples
      indicated various functionalities on the biomass surface including carboxyl,
      hydroxyl, and amino and sulphonate groups which are responsible for the binding
      of metal ions. CONCLUSIONS: The capacity of the biomass for single metal ions
      (around 1 mmol/g) was increased to 1.3 mmol/g in competitive adsorption, Pb(II)
      showing the highest Langmuir intensity constant. Considering its extremely high
      abundance and low cost, C. barbata may be potentially important in metal ion
      removal from contaminated water and industrial effluents.

PMID- 22875423
TI  - Dynamics of phosphorus forms in the bottom sediments and their interstitial water
      for the Prut River (Moldova).
AB  - Phosphorus concentration in rivers results from both external inputs and internal
      loading from the bottom sediments. Seasonal, spatial, and multi-annual dynamics
      of phosphorus forms in bottom sediments and their interstitial water for the
      river Prut (Moldova) were evaluated. In order to determine content of total
      phosphorus in the bottom sediments, fresh (wet) samples were subjected to
      persulfate oxidation. The content of inorganic phosphorus was determined after
      acidic oxidation of samples. The amount of organic phosphorus was obtained by
      subtracting inorganic phosphorus from the amount of total phosphorus. Content of
      phosphorus forms in interstitial water was determined after centrifugation of
      fresh (wet) sediments. In general, the shape of dynamics of the amounts of
      inorganic phosphorus in sediments was close during years 2009, 2010, and 2011,
      with registered higher contents of this form on the middle course of the river.
      The spatial dynamics of organic phosphorus is less homogeneous along the Prut
      River. During 2009, higher amounts of organic phosphorus were recorded on the
      middle sector. During the spring of year 2010, the content of organic phosphorus
      in sediments was practically not changed along the river. The ratio of
      inorganic/organic phosphorus in bottom sediments was similar during the
      researched years, with the predominance of the inorganic phosphorus being
      recorded. Also, the increasing tendency of the percentage of organic phosphorus
      from spring to summer was identified. Generally, appropriate spatial and seasonal
      dynamics of phosphorus forms in bottom sediments and their interstitial water
      were recorded, although sometimes with some differences.

PMID- 22875424
TI  - An integrated approach to identify the origin of PM10 exceedances.
AB  - PURPOSE: This study was aimed to the development of an integrated approach for
      the characterization of particulate matter (PM) pollution events in the South of
      Italy. METHODS: PM(10) and PM(2.5) daily samples were collected from June to
      November 2008 at an urban background site located in Bari (Puglia Region, South
      of Italy). Meteorological data, particle size distributions and atmospheric
      dispersion conditions were also monitored in order to provide information
      concerning the different features of PM sources. RESULTS: The collected data
      allowed suggesting four indicators to characterize different PM(10) exceedances.
      PM(2.5)/PM(10) ratio, natural radioactivity, aerosol maps and back-trajectory
      analysis and particle distributions were considered in order to evaluate the
      contribution of local anthropogenic sources and to determine the different
      origins of intrusive air mass coming from long-range transport, such as African
      dust outbreaks and aerosol particles from Central and Eastern Europe. The
      obtained results were confirmed by applying principal component analysis to the
      number particle concentration dataset and by the chemical characterization of the
      samples (PM(10) and PM(2.5)). CONCLUSIONS: The integrated approach for PM study
      suggested in this paper can be useful to support the air quality managers for the
      development of cost-effective control strategies and the application of more
      suitable risk management approaches.

PMID- 22875425
TI  - GC-MS analyses and chemometric processing to discriminate the local and long
      distance sources of PAHs associated to atmospheric PM2.5.
AB  - PURPOSE: This study presents a procedure to differentiate the local and remote
      sources of particulate-bound polycyclic aromatic hydrocarbons (PAHs). METHODS:
      Data were collected during an extended PM(2.5) sampling campaign (2009-2010)
      carried out for 1 year in Venice-Mestre, Italy, at three stations with different
      emissive scenarios: urban, industrial, and semirural background. Diagnostic
      ratios and factor analysis were initially applied to point out the most probable
      sources. In a second step, the areal distribution of the identified sources was
      studied by applying the discriminant analysis on factor scores. Third, samples
      collected in days with similar atmospheric circulation patterns were grouped
      using a cluster analysis on wind data. Local contributions to PM(2.5) and PAHs
      were then assessed by interpreting cluster results with chemical data. RESULTS:
      Results evidenced that significantly lower levels of PM(2.5) and PAHs were found
      when faster winds changed air masses, whereas in presence of scarce ventilation,
      locally emitted pollutants were trapped and concentrations increased. This way,
      an estimation of pollutant loads due to local sources can be derived from data
      collected in days with similar wind patterns. Long-range contributions were
      detected by a cluster analysis on the air mass back-trajectories. Results
      revealed that PM(2.5) concentrations were relatively high when air masses had
      passed over the Po Valley. However, external sources do not significantly
      contribute to the PAHs load. CONCLUSIONS: The proposed procedure can be applied
      to other environments with minor modifications, and the obtained information can
      be useful to design local and national air pollution control strategies.

PMID- 22875426
TI  - Bullying in childhood and religious/spiritual status in adulthood among internal
      medicine outpatients.
AB  - BACKGROUND: Bullying in childhood is ubiquitous and associated with a number of
      identified negative outcomes in both childhood and adulthood. However, the
      relationship between being bullied in childhood and religious/spiritual status in
      adulthood has never been explored. METHOD: Using a cross-sectional sample of 324
      consecutive internal medicine outpatients and a survey methodology, we examined
      relationships between 'When you were growing up, were you ever a victim of
      bullying?' and (1) self-perceived extent of religiosity/spirituality and (2)
      religiosity/spirituality as assessed by scores on the Functional Assessment of
      Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp-12). RESULTS: While
      bullying status in childhood was not related to either the self-perceived extent
      of religiosity or spirituality, it did evidence negative statistically
      significant relationships with seven of 12 FACIT-Sp-12 scales, as well as the
      overall composite score. CONCLUSIONS: According to these data, bullying in
      childhood is associated with lower religious/spiritual well-being in adulthood;
      however, this study was not designed to examine a causal relationship.

PMID- 22875427
TI  - Metal on metal implants: where are we now and what should happen next?

PMID- 22875428
TI  - Perioperative management of adults with diabetes: why do we need guidance?

PMID- 22875430
TI  - Hair loss in hospital medicine:  a practical guide.
AB  - Alopecia may indicate underlying systemic disease and is associated with
      significant impairment of quality of life. A thorough history and examination,
      including specialist techniques, can give vital clues to the aetiology. This
      article provides an overview of the common and important hair loss disorders for
      the busy clinician.

PMID- 22875431
TI  - Diagnosis, epidemiology and treatment of inflammatory neuropathies.
AB  - This article reviews the main diagnostic, epidemiological and therapeutic issues
      relating to the three main inflammatory neuropathies: Guillain-Barre syndrome,
      chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor
      neuropathy. The current knowledge base and recent developments are described.

PMID- 22875432
TI  - Meticillin-resistant  Staphylococcus aureus pneumonia.
AB  - Meticillin-resistant Staphylococcus aureus causes an evolving clinical
      presentation of pneumonia. Health-care-acquired infection differs from community
      associated disease, with important implications for treatment. Current
      antibiotics are less than ideal, and broader management strategies are crucial to
      prevent complacency.

PMID- 22875433
TI  - Medical revalidation:  a route to excellence?
AB  - All doctors who hold a licence to practise will need to revalidate every 5 years.
      The process includes the consideration of defined items of supporting information
      at five annual appraisals. These essentials must support professional development
      and the achievement of excellence in patient care.

PMID- 22875434
TI  - Leading change in health-care quality with the Institute for Healthcare
      Improvement Open School.
AB  - The Institute for Healthcare Improvement Open School for Health Professions is an
      international organization that provides the next generation of health-care
      leaders with the skills to lead improvement in health care. This article
      discusses how doctors can get involved and implement change at their hospital.

PMID- 22875435
TI  - Medical students' views and understanding of a career in academic medicine.
AB  - Academic medicine is crucial to the advancement of health care with
      responsibilities in research, teaching and clinical practice. There have been
      problems recently recruiting for academic posts. This article illustrates medical
      students' views and understanding of a career in academic medicine.

PMID- 22875436
TI  - The cutting edge of medicine 50 years ago.

PMID- 22875438
TI  - HIV dementia: a diagnosis to keep in mind.

PMID- 22875439
TI  - gamma-Hydroxybutyrate toxicity mimicking basilar artery stroke.

PMID- 22875440
TI  - Multidisciplinary team working.

PMID- 22875441
TI  - Planning ahead for your retirement.

PMID- 22875443
TI  - Facemask ventilation before neuromuscular blockade?

PMID- 22875444
TI  - Extreme tortuosity of the iliac artery.

PMID- 22875445
TI  - Unusual malignant ureteral obstruction and management.

PMID- 22875446
TI  - Stress-induced myocardial ischemia is associated with early post-stress left
      ventricular mechanical dyssynchrony as assessed by phase analysis of 201Tl gated
      SPECT myocardial perfusion imaging.
AB  - PURPOSE: In (201)Tl SPECT myocardial perfusion imaging (MPI) data are acquired
      shortly after the stress injection to assess early post-stress left ventricle
      (LV) function. The purpose of this study was to use (201)Tl SPECT MPI to
      investigate whether stress-induced myocardial ischemia is associated with LV
      mechanical dyssynchrony. METHODS: Enrolled in the study were 75 patients who were
      referred for dipyridamole stress and rest (201)Tl gated SPECT MPI. The early post
      stress scan was started 5 min after injection, and followed by the rest scan 4 h
      later. The patients were divided into three groups: ischemia group (N = 25,
      summed stress score, SSS, >=5, summed rest score, SRS, <5), infarct group (N =
      16, SSS >=5, SRS >=5) and normal group (N = 34, SSS <5, SRS <5). LV dyssynchrony
      parameters were calculated by phase analysis, and compared between the stress and
      rest images. RESULTS: In the ischemia group, LV dyssynchrony was significantly
      larger during stress than during rest. On the contrary, LV dyssynchrony during
      stress was significantly smaller than during rest in the normal and infarct
      groups. LV dyssynchrony during rest was significantly larger in the infarct group
      than in the normal and ischemia groups. There were no significant differences in
      LV dyssynchrony during rest between the normal and ischemia groups. CONCLUSION:
      Stress-induced myocardial ischemia caused dyssynchronous contraction in the
      ischemic region, leading to a deterioration in LV synchrony. Normal myocardium
      had more synchronous contraction during stress. The different dyssynchrony
      pattern between ischemic and normal myocardium early post-stress may aid the
      diagnosis of coronary artery disease using (201)Tl gated SPECT MPI.

PMID- 22875447
TI  - Metal-filled carbon nanotube based optical nanoantennas: bubbling, reshaping, and
      in situ characterization.
AB  - Controlled fabrication of metal nanospheres on nanotube tips for optical antennas
      is investigated experimentally. Resembling soap bubble blowing using a straw, the
      fabrication process is based on nanofluidic mass delivery at the attogram scale
      using metal-filled carbon nanotubes (m@CNTs). Two methods have been investigated
      including electron-beam-induced bubbling (EBIB) and electromigration-based
      bubbling (EMBB). EBIB involves the bombardment of an m@CNT with a high energy
      electron beam of a transmission electron microscope (TEM), with which the
      encapsulated metal is melted and flowed out from the nanotube, generating a
      metallic particle on a nanotube tip. In the case where the encapsulated materials
      inside the CNT have a higher melting point than what the beam energy can reach,
      EMBB is an optional process to apply. Experiments show that, under a low bias
      (2.0-2.5 V), nanoparticles can be formed on the nanotube tips. The final shape
      and crystallinity of the nanoparticles are determined by the cooling rate.
      Instant cooling occurs with a relatively large heat sink and causes the instant
      shaping of the solid deposit, which is typically similar to the shape of the
      molten state. With a smaller heat sink as a probe, it is possible to keep the
      deposit in a molten state. Instant cooling by separating the deposit from the
      probe can result in a perfect sphere. Surface and volume plasmons characterized
      with electron energy loss spectroscopy (EELS) prove that resonance occurs between
      a pair of as-fabricated spheres on the tip structures. Such spheres on pillars
      can serve as nano-optical antennas and will enable devices such as scanning near
      field optical microscope (SNOM) probes, scanning anodes for field emitters, and
      single molecule detectors, which can find applications in bio-sensing, molecular
      detection, and high-resolution optical microscopy.

PMID- 22875449
TI  - Communicating with our external and internal environments.

PMID- 22875450
TI  - Optimizing cholinergic tone through lynx modulators of nicotinic receptors:
      implications for plasticity and nicotine addiction.
AB  - The cholinergic system underlies both adaptive (learning and memory) and
      nonadaptive (addiction and dependency) behavioral changes through its ability to
      shape and regulate plasticity. Protein modulators such as lynx family members can
      fine tune the activity of the cholinergic system and contribute to the graded
      response of the cholinergic system, stabilizing neural circuitry through direct
      interaction with nicotinic receptors. Release of this molecular brake can unmask
      cholinergic-dependent mechanisms in the brain. Lynx proteins have the potential
      to provide top-down control over plasticity mechanisms, including addictive
      propensity. If this is indeed the case, then, what regulates the regulator?
      Transcriptional changes of lynx genes in response to pharmacological,
      physiological, and pathological alterations are explored in this review.

PMID- 22875451
TI  - Odorant receptors in the formation of the olfactory bulb circuitry.
AB  - In mammals, smell is mediated by odorant receptors expressed by sensory neurons
      in the nose. These specialized receptors are found both on olfactory sensory
      neurons' cilia and axon terminals. Although the primary function of ciliary
      odorant receptors is to detect odorants, their axonal role remains unclear but is
      thought to involve axon guidance. This review discusses findings that show axonal
      odorant receptors are indeed functional and capable of modulating neural
      connectivity.

PMID- 22875452
TI  - An inside view: VEGF receptor trafficking and signaling.
AB  - Vascular endothelial growth factors (VEGF) and their receptors play a central
      role in the development of cardiovascular system and in vasculature-related
      processes in the adult organism. Given the critical role of this signaling
      cascade, intricate control systems have evolved to regulate its function. A new
      layer of  added complexity has been the demonstration of the importance of
      endocytosis and intracellular trafficking of VEGF receptors in the regulation of
      VEGF signaling. In this review, we consider an evolving link between VEGF
      receptor endocytosis, trafficking, and signaling and their biological function.

PMID- 22875453
TI  - Endocytic receptors in the renal proximal tubule.
AB  - Protein reabsorption is a predominant feature of the renal proximal tubule.
      Animal studies show that the ability to rescue plasma proteins relies on the
      endocytic receptors megalin and cubilin. Recently, studies of patients with
      syndromes caused by dysfunctional receptors have supported the importance of
      these for protein clearance of human ultrafiltrate. This review focuses on the
      molecular biology and physiology of the receptors and their involvement in renal
      pathological conditions.

PMID- 22875455
TI  - Phosphodiesterases and cyclic GMP regulation in heart muscle.
AB  - The cyclic nucleotide cGMP and its corresponding activated kinase cGK-1 serve as
      a counterbalance to acute and chronic myocardial stress. cGMP hydrolysis by
      several members of the phosphodiesterase (PDE) superfamily, PDE1, PDE2, and PDE5,
      regulate this signaling in the heart. This review details new insights regarding
      how these PDEs modulate cGMP and cGK-1 to influence heart function and chronic
      stress responses, and how their inhibition may provide potential therapeutic
      benefits.

PMID- 22875454
TI  - The barrier within: endothelial transport of hormones.
AB  - Hormones are involved in a plethora of processes including development and
      growth, metabolism, mood, and immune responses. These essential functions are
      dependent on the ability of the hormone to access its target tissue. In the case
      of endocrine hormones that are transported through the blood, this often means
      that the endothelium must be crossed. Many studies have shown that the
      concentrations of hormones and nutrients in blood can be very different from
      those surrounding the cells on the tissue side of the blood vessel endothelium,
      suggesting that transport across this barrier can be rate limiting for hormone
      action. This transport can be regulated by altering the surface area of the blood
      vessel available for diffusion through to the underlying tissue or by the
      permeability of the endothelium. Many hormones are known to directly or
      indirectly affect the endothelial barrier, thus affecting their own distribution
      to their target tissues. Dysfunction of the endothelial barrier is found in many
      diseases, particularly those associated with the metabolic syndrome. The
      interrelatedness of hormones may help to explain why the cluster of diseases in
      the metabolic syndrome occur together so frequently and suggests that treating
      the endothelium may ameliorate defects in more than one disease. Here, we review
      the structure and function of the endothelium, its contribution to the function
      of hormones, and its involvement in disease.

PMID- 22875456
TI  - The combinatorial nature of osmosensing in fishes.
AB  - Organisms exposed to altered salinity must be able to perceive osmolality change
      because metabolism has evolved to function optimally at specific intracellular
      ionic strength and composition. Such osmosensing comprises a complex
      physiological process involving many elements at organismal and cellular levels
      of organization. Input from numerous osmosensors is integrated to encode
      magnitude, direction, and ionic basis of osmolality change. This combinatorial
      nature of osmosensing is discussed with emphasis on fishes.

PMID- 22875457
TI  - FGF23: instability may affect accuracy and interpretation.

PMID- 22875458
TI  - Lack of predictive value of FGF23 levels on pulse wave velocity.

PMID- 22875460
TI  - Recurrent bilateral metatarsal "stress-and-insufficiency" fractures in a levodopa
      treated young woman with Parkinson's disease.
AB  - Levodopa treatment of Parkinson's disease is very effective, but many types of
      adverse events can complicate the disease course, especially dyskinesias. As
      reported by Lee et al. (Calcif Tissue Int 86:132-41, 2010), levodopa intake is
      associated with increased homocysteinemia that is known to be linked to poorer
      bone quality and, consequently, osteoporotic fractures. Herein, we report the
      case of a young woman who suffered recurrent metatarsal fractures in the context
      of levodopa-treated early-onset Parkinson's disease.

PMID- 22875459
TI  - Bone metabolism in anorexia nervosa: molecular pathways and current treatment
      modalities.
AB  - Eating disorders are associated with a multitude of metabolic abnormalities which
      are known to adversely affect bone metabolism and structure. We aimed to
      comprehensively review the literature on the effects of eating disorders,
      particularly anorexia nervosa (AN), on bone metabolism, bone mineral density
      (BMD), and fracture incidence. Furthermore, we aimed to highlight the risk
      factors and potential management strategies for patients with eating disorders
      and low BMD. We searched the MEDLINE/OVID (1950-July 2011) and EMBASE (1980-July
      2011) databases, focussing on in vitro and in vivo studies of the effects of
      eating disorders on bone metabolism, bone mineral density, and fracture
      incidence. Low levels of estrogen, testosterone, dehydroepiandrosterone, insulin
      like growth factor-1 (IGF-1), and leptin, and high levels of cortisol, ghrelin,
      and peptide YY (PYY) are thought to contribute to the 'uncoupling' of bone
      turnover in patients with active AN, leading to increased bone resorption in
      comparison to bone formation. Over time, this results in a high prevalence and
      profound degree of site-specific BMD loss in women with AN, thereby increasing
      fracture risk. Weight recovery and increasing BMI positively correlate with
      levels of IGF-1 and leptin, normalisation in the levels of cortisol, as well as
      markers of bone formation and resorption in both adolescent and adult patients
      with AN. The only treatments which have shown promise in reversing the BMD loss
      associated with AN include: physiologic dose transdermal and oral estrogen,
      recombinant human IGF-1 alone or in combination with the oral contraceptive pill,
      and bisphosphonate therapy.

PMID- 22875461
TI  - Delayed primary anastomosis for management of long-gap esophageal atresia: a meta
      analysis of complications and long-term outcome.
AB  - PURPOSE: Management of newborns with long-gap esophageal atresia (LGEA) remains a
      challenge for pediatric surgeons. Since spontaneous growth of the esophageal
      segments occurs without mechanical stretching, initial gastrostomy followed by
      delayed primary anastomosis (DPA) comprises treatment in most LGEA patients. This
      meta-analysis aimed to investigate the complications and long-term outcome in
      patients with LGEA managed by DPA. METHODS: A systematic literature search was
      conducted for relevant articles published between 1981 and 2011, and a meta
      analysis of complications and long-term outcome was performed. RESULTS: Forty
      four articles presented data on 451 newborns with LGEA managed by DPA. Most
      common variants were pure LGEA (194/451) and LGEA with tracheoesophageal fistula
      (257/451). Initial gap lengths ranged from 1.9 to 7.0 cm. At the time of DPA,
      performed at a mean of 11.9 weeks (range 0.5-54.0), the gap had decreased to 0.5
      3.0 cm. Mean follow-up was 5.5 years (range 0.5-27.0). Frequent complications
      were anastomotic leaks/strictures, gastroesophageal reflux (GER), esophagitis and
      dysphagia. Relative risk for strictures was significantly higher in patients who
      previously had a leak (p < 0.0001) or GER (p < 0.0001). Patients with GER also
      had a significantly higher risk for esophagitis (p = 0.0283) and dysphagia (p =
      0.0174). The majority of patients could eat without swallowing difficulties at
      follow-up. CONCLUSION: DPA provides good long-term functional results. However,
      the high incidence of GER and associated strictures requires early intervention
      to prevent feeding problems.

PMID- 22875462
TI  - Pulmonary artery size as an indication for thoracoscopic repair of congenital
      diaphragmatic hernia in neonates.
AB  - PURPOSE: We reviewed 24 consecutive cases of prenatally or immediately
      postnatally diagnosed left-sided congenital diaphragmatic hernia (CDH) to
      evaluate pulmonary artery (PA) size as an indication for thoracoscopic repair
      (TR). METHODS: CDH repair is planned once echocardiography confirms improvement
      in pulmonary hypertension. TR is chosen if cardiopulmonary status is stable more
      than 10 min in the decubitus position in the neonatal intensive care unit (NICU)
      under conventional mechanical or high frequency oscillatory ventilation (HFOV)
      with/without nitric oxide (NO) and the patient appears likely to tolerate manual
      ventilation during transfer to the operating room. Otherwise open repair (OR) is
      performed in NICU. Proximal right PA (RPA) and left PA (LPA) diameters measured
      at birth were assessed with respect to the type of repair. RESULTS: 10/24 had TR
      and 14/24 had OR. TR cases had significantly larger RPA/LPA diameters (3.52 +/-
      0.23 vs. 3.10 +/- 0.56 mm, p < 0.05 for RPA; 3.04 +/- 0.26 vs. 2.48 +/- 0.37, p <
      0.01 for LPA), and significantly less requirement for HFOV (70 vs. 100 %, p <
      0.05) and NO (20 vs. 86 %, p < 0.01). Four TR required conversion to OR for
      technical reasons (n = 3) and cardiopulmonary instability (n = 1). CONCLUSIONS:
      TR can be considered when RPA/LPA diameters are larger than 3.0/2.5 mm,
      respectively, and cardiopulmonary status is stable without NO.

PMID- 22875463
TI  - Laparoscopic inguinal hernia repair in premature babies weighing 3 kg or less.
AB  - PURPOSE: This retrospective study aims to evaluate the feasibility, safety and
      complication rate of laparoscopic inguinal hernia repair for small babies
      weighing 3 kg or less. METHODS: A retrospective analysis was performed on the
      surgical charts of 67 infants (47 boys and 20 girls) weighing 3 kg or less who
      underwent laparoscopic hernia repair in a 3-year period. A regular 5-mm scope was
      used for visualization, and 2 or 3-mm instruments were used for the closure of
      the inner inguinal ring using 3/0 non-absorbable suture. The median weight at
      surgery was 2,600 g (range 1,450-3,000 g). All except three were premature.
      RESULTS: Of the 67 infants, 15 (22.3 %) presented with an irreducible hernia. In
      three cases of irreducible hernias, we also performed a transumbilical
      appendectomy at the end of the hernia repair. Minor problems related with
      anesthesia were noted in four cases. Hernia recurrence was observed in three
      patients (4.4 %). No cases of testicular atrophy occurred. In 10 boys, we
      observed 12 cases of high testes, only 4 testes requiring subsequent orchiopexy.
      CONCLUSIONS: Laparoscopic inguinal hernia repair for babies weighing 3 kg or less
      is feasible, safe and perhaps even less technically demanding than open inguinal
      herniotomy.

PMID- 22875464
TI  - Not worth the fuss after all? cross-sectional and prospective data on violent
      video game influences on aggression, visuospatial cognition and mathematics
      ability in a sample of youth.
AB  - The United States Supreme Court's recent decision relating to violent video games
      revealed divisions within the scientific community about the potential for
      negative effects of such games as well as the need for more, higher quality
      research. Scholars also have debated the potential for violent games to have
      positive effects such as on visuospatial cognition or math ability. The current
      study sought to extend previous literature by using well-validated clinical
      outcome measures for relevant constructs, which have generally been lacking in
      past research. Cross-section data on aggression, visuospatial cognition, and math
      achievement were available for a sample of 333 (51.7 % female) mostly Hispanic
      youth (mean age = 12.76). Prospective 1-year data on aggression and school GPA
      were available for 143 (46.2 % female) of those youth. Results from both sets of
      analysis revealed that exposure to violent game had neither short-term nor long
      term predictive influences on either positive or negative outcomes. A
      developmental analysis of the cross-sectional data revealed that results did not
      differ across age categories of older children, preadolescents or adolescents.
      Analysis of effect sizes largely ruled out Type II error as a possible
      explanation for null results. Suggestions for new directions in the field of
      video game research are proffered.

PMID- 22875465
TI  - Bioaccumulation of metals (Cd, Cu, Zn) by the marine bivalves M.
      galloprovincialis, P. radiata, V. verrucosa and C. chione in Mediterranean
      coastal microenvironments: association with metal bioavailability.
AB  - The concentrations of Cd, Cu and Zn in both the whole soft tissue and separate
      organs (gills, mantle, muscle and digestive gland) of wild bivalves (Mytilus
      galloprovincialis, Pinctada radiata, Venus verrucosa and Callista chione) from
      three different coastal microenvironments of Greece were monitored from 2003 to
      2004. In parallel, by employing appropriate analytical protocols for metal
      partitioning, the labile fraction of the metals was determined in the dissolved
      phase, suspended particulate matter and sediments. Differences in the metal
      levels were detected both among the study areas as well as among the bivalves
      examined. Significant bioaccumulation was demonstrated regarding Zn in M.
      galloprovincialis specimens from the highly industrialized Gulf of Elefsis and Cd
      in P. radiata and V. verrucosa from the Maliakos Gulf, which is influenced by
      extended agricultural activity occurring at the neighbouring area and a river
      outflow. Data of the metal levels in the various environmental phases were
      correlated with their concentrations in bivalves' tissues. The clear
      relationships obtained in many cases among the labile metal concentrations and
      the bioaccumulated concentrations in bivalves point out that the labile fraction
      of a metal is the most bioavailable. The lack of positive correlation for C.
      chione confirms the occurrence of effective mechanisms of internal regulation of
      metal concentrations.

PMID- 22875466
TI  - In situ generated "lanthanum(III) nitrate alkoxide" as a highly active and nearly
      neutral transesterification catalyst.
AB  - In situ generated lanthanum(III) nitrate alkoxide is a highly active and nearly
      neutral transesterification catalyst, which can promote non-epimerized
      transesterification of alpha-substituted chiral carboxylic esters under reflux
      conditions.

PMID- 22875467
TI  - Cytolytic peptide fragments of Cyt1Aa from Bacillus thuringiensis subsp.
      israelensis.
AB  - Cyt1Aa is the major and most active component of the parasporal crystal of the
      Gram-positive soil entomopathogenic bacterium Bacillus thuringiensis subsp.
      israelensis. The Cyt1Aa protoxin exhibits some hemolytic and cytolytic activity.
      However, highly active 22-25 kDa toxins are obtained after proteolysis of Cyt1Aa
      from both the N- and the C-termini. As shown in this study, preliminary binding
      of the protoxin to polylamellary liposomes or partial denaturation of Cyt1Aa and
      further processing by several exogenous proteases yielded short 4.9-11.5 kDa
      cytolytic peptide fragments of Cyt1Aa. The shortest 51 amino acid peptide was
      obtained after pre-incubation of Cyt1Aa with SDS and proteolysis with proteinase
      K. This peptide was purified, identified as the Ile87-Asp137 fragment of Cyt1Aa
      and was shown to exhibit more than 30 % hemolysis of rabbit erythrocytes.

PMID- 22875469
TI  - Early-diastolic left ventricular lengthening implies pulmonary hypertension
      induced right ventricular decompensation.
AB  - AIMS: In chronic pulmonary hypertension (PH), right ventricular (RV) failure is
      associated with shortening of the RV free wall (RVFW) beyond pulmonary valve
      closure, temporarily paralleled by pronounced lengthening of the left ventricular
      free wall (LVFW). We hypothesized that this early-diastolic LVFW lengthening is
      caused by altered RVFW myofibre function and may therefore serve as a non
      invasive measure of PH-induced RV (dys)function. METHODS AND RESULTS: In 22
      idiopathic pulmonary arterial hypertension (IPAH) patients, five chronic thrombo
      embolic PH (CTEPH) patients, and six healthy subjects, ventricular volumes and
      circumferential strains were obtained using magnetic resonance imaging. RV
      ejection fraction (RVEF) and stroke volume index (RVSVI) were smaller in IPAH and
      CTEPH patients than in normals (RVEF: 32 +/- 12 and 23 +/- 19 vs. 59 +/- 14%,
      respectively, both P < 0.01; RVSVI: 32 +/- 9 and 23 +/- 9 vs. 47 +/- 6 mL/m(2),
      both P < 0.001). LV early-diastolic strain index (LVEDSI), defined as LVFW strain
      in the period between LVFW and RVFW peak shortening normalized for total systolic
      LVFW shortening, was larger in IPAH and CTEPH patients (0.52 +/- 0.33 and 0.55 +/
      0.40, both P < 0.01) than in normals (-0.03 +/- 0.03). LVEDSI correlated
      negatively with RVEF (R = -0.74, P < 0.0001) and RVSVI (R = -0.69, P < 0.0001).
      Three multi-scale computer simulations of PH (all with mean pulmonary artery
      pressure = 55 mmHg) with complete, incomplete, and no structural adaptation of
      ventricular walls to local myofibre load showed that LVEDSI increased with
      deficiency of cardiac adaptation to PH (0.01, 0.52, and 0.84, respectively).
      CONCLUSION: Early-diastolic LV lengthening reflects inadequate structural
      adaptation of the RVFW to increased myofibre load and is therefore a useful, non
      invasive, and easily obtainable predictor of PH-induced RV dysfunction.

PMID- 22875468
TI  - SOCS1 gene transfer accelerates the transition to heart failure through the
      inhibition of the gp130/JAK/STAT pathway.
AB  - AIMS: The suppressors of cytokine signalling (SOCS) are identified inhibitors of
      cytokine and growth factor signalling that act via the Janus kinase (JAK) signal
      transducers and activators of transcription (STAT) pathways. Aberrant JAK/STAT
      signalling promotes progression from hypertrophy to heart failure. Little
      information is available concerning the role of SOCS in the transition from
      hypertrophy to heart failure. To this aim, we investigated the effects of SOCS1
      overexpression obtained by in vivo adeno-associated gene transfer using an
      aortopulmonary cross-clamping technique in a chronic pressure-overload cardiac
      rat model. METHODS AND RESULTS: Rats were randomized into four groups: sham
      operated (n = 18), aortic banding (AB) (n = 18), AB + viral vector encoding for
      haemoagglutinin (AB + HA, n = 16), and AB + viral vector encoding for SOCS1 (AB +
      SOCS1, n = 18). Echocardiographic and haemodynamic measurements were performed 15
      weeks after banding. While SOCS3 was upregulated during the hypertrophic phase,
      SOCS1 transcript levels increased significantly between 15 and 20 weeks.
      Remodelling was markedly worse in AB + SOCS1, showed larger left ventricular
      internal dimensions (+16%), higher end-diastolic pressures (+57%) and wall stress
      (+45%), and reduced fractional shortening (-32%) compared with AB + HA; apoptotic
      rate was increased three-fold and the gp130 pathway was inhibited. Ex vivo
      experiments showed that mechanical stretch upregulated SOCS1 expression, which
      was in turn attenuated by tumour necrosis factor-alpha (TNF-alpha) inhibition.
      CONCLUSION: Enhanced SOCS1 myocardial signalling is associated with accelerated
      transition from hypertrophy to failure in an established model of pressure
      overload. SOCS1 may represent an attractive target for the prevention of heart
      failure progression.

PMID- 22875470
TI  - Resilience among urban American Indian adolescents: exploration into the role of
      culture, self-esteem, subjective well-being, and social support.
AB  - The effects of enculturation, self-esteem, subjective well-being, and social
      support on resilience among urban American Indian (AI) adolescents from a South
      Central region of the U.S. were explored. Of the 196 participants, 114 (58.2%)
      were female and 82 (41.8%) were male (ages 14-18 years). Thirty-three percent of
      the variance in resilience was accounted for by enculturation, self-esteem, and
      social support, while 34% of the variance in resilience was contributed by
      enculturation, subjective well-being, and social support. However, social support
      from friends remained the strongest predictor.

PMID- 22875471
TI  - The power of protection: a population-based comparison of Native and non-Native
      youth suicide attempters.
AB  - This study provides actionable information about intervening with American
      Indian/Alaska Native (AI/AN) youth to prevent suicide. Statewide school survey
      data were used to model the impact of risk and protective factors on self
      reported suicide attempts (both AI/AN and non-AI/AN). The cumulative risk and
      protective model worked similarly for both groups. AI/AN youth had a higher
      threshold of risk before making a suicide attempt. Protective factors buffered
      the impact of risk, particularly for the higher risk youth.

PMID- 22875472
TI  - Does a culturally sensitive smoking prevention program reduce smoking intentions
      among Aboriginal children? A pilot study.
AB  - The aim of the study was to determine if a culturally sensitive smoking
      prevention program would have short-term impacts on smoking intentions among
      Aboriginal children. Two schools with high Aboriginal enrollment were selected
      for the study. A grade 4 classroom in one school was randomly assigned to receive
      the culturally sensitive smoking prevention program. A grade 4 classroom in the
      second school received a standard smoking prevention program delivered in this
      jurisdiction. Children in each classroom were tested pre- and post-intervention
      to measure attitude changes about smoking. There was a significant reduction in
      intentions to smoke among Aboriginal children who received the culturally
      sensitive smoking prevention program. The small overall sample size precluded a
      direct comparison of the efficacy of the culturally sensitive and standard
      programs. The present findings suggest a smoking prevention program that has been
      culturally adapted for Aboriginal children may reduce future smoking intentions
      among Aboriginal grade 4 students. Further research is needed to determine the
      extent to which school smoking prevention programs adapted to respect the long
      standing use of tobacco in Aboriginal cultural traditions may be more effective
      than standard programs in reaching Aboriginal youth.

PMID- 22875473
TI  - Inhibition of hepatocellular carcinoma by PegIFNalpha-2a in patients with chronic
      hepatitis C: a nationwide multicenter cooperative study.
AB  - BACKGROUND: We investigated whether the administration of maintenance doses of
      interferon prevented hepatocellular carcinoma (HCC) in patients with chronic
      hepatitis C. METHODS: Study 1: A multicenter, retrospective, cooperative study
      was carried out to determine whether long-term administration of low-dose
      peginterferon alpha-2a (PegIFNalpha-2a) prevented HCC development in patients
      with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a
      history of HCC were enrolled and treated with 90 MUg PegIFNalpha-2a administered
      weekly or bi-weekly for at least 1 year. Study 2: HCC developed in 16 of 99
      additional patients without PegIFNalpha-2a treatment during 3.8 years of
      observation. A propensity-matched control study was then carried out to compare
      the incidence of HCC between the 59 patients who received low-dose PegIFNalpha-2a
      (PegIFNalpha-2a group) and 59 patients who did not receive PegIFNalpha-2a
      treatment (control group), matched for sex, age, platelet count, and total
      bilirubin levels. RESULTS: Study 1: HCC developed in 49 patients. The risk of HCC
      was lower in patients with undetectable hepatitis C virus RNA, <=40 IU/L alanine
      aminotransferase (ALT), or <=10 ng/L alpha-fetoprotein (AFP) 24 weeks after the
      start of therapy. Study 2: The incidence of HCC was significantly lower in the
      PegIFNalpha-2a group than in the control group. CONCLUSIONS: Low-dose and long
      term maintenance administration of PegIFNalpha-2a decreased the incidence of HCC
      in patients with normalized ALT and AFP levels at 24 weeks compared with patients
      without normal ALT and AFP levels.

PMID- 22875475
TI  - Modeling of graphene nanoribbon devices.
AB  - Recent advances in graphene nanoribbon (GNR) electronic devices provide a
      concrete context for developing simulation methods, comparing theories to
      experiments, and using simulations to explore device physics. We present a review
      on modeling of graphene nanoribbon devices, with an emphasis on electronic and
      magnetoresistive devices. Device modeling is reviewed in a synergistic
      perspective with GNR material properties, device characteristics, and circuit
      requirements. Similarity with and difference to carbon nanotube devices are
      discussed. Device modeling and simulation results are compared to experimental
      data, which underlines the importance of theory-experiment collaborations in this
      field. Importance of the GNR edges, which have a negative impact on the carrier
      mobility due to edge roughness but offer new possibilities of spintronic devices
      and edge doping, is emphasized. Advanced device modeling of GNRs needs to have
      the capability to describe GNR device physics, including three-dimensional
      electrostatics, quantum and atomistic scale effects, elastic and inelastic
      scattering processes, electron-electron interaction, edge chemistry, magnetic
      field modulation, and spintronic and thermoelectric device phenomena.

PMID- 22875474
TI  - NSAID enteropathy: could probiotics prevent it?
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used
      drugs in the world; nevertheless, about 50-70% of patients on long-term NSAIDs
      develop small intestine injury, namely NSAID enteropathy, sometimes with serious
      outcomes. No medications with proven efficacy are yet available to prevent NSAID
      enteropathy. A series of therapeutic strategies targeting the different
      mechanisms involved in small bowel injury have been investigated, but without
      definitive results. Intestinal bacteria and their degradation products are
      essential for the development of NSAID-induced small bowel lesions, because "germ
      free" animals were found to be resistant to indomethacin injuries. Therefore, it
      has been suggested that modulating the intestinal flora, for example by using
      probiotics, could protect against NSAID enteropathy. In this work, we reviewed
      the main therapeutic strategies for NSAID enteropathy, in particular analyzing
      the available studies relating to the eventual protective role of probiotics. We
      found that results are not all concordant; nevertheless, the more recent studies
      provide better understanding about pathogenetic mechanisms involved in small
      intestinal injury and the role of probiotics, and show encouraging results.
      Larger and well-designed studies should be performed to evaluate the actual role
      of probiotics in NSAID enteropathy, the eventual differences among probiotic
      strains, dose-responses, and optimal duration of therapy.

PMID- 22875476
TI  - Oncology imaging in the abdomen and pelvis: where cancer hides.
AB  - As the incidence of cancer continues to increase, imaging will play an ever more
      important role in the detection, diagnosis, staging, surveillance, and
      therapeutic monitoring of cancer. Diagnostic errors in the initial discovery of
      cancer or at follow-up assessments can lead to missed opportunities for curative
      treatments or altering or reinitiating therapies, as well as adversely impact
      clinical trials. Radiologists must have an understanding of cancer biology,
      treatments, and imaging appearance of therapeutic effects and be mindful that
      metastatic disease can involve virtually any organ system. Knowledge of patient
      history and tumor biology allows for optimizing imaging protocols. The majority
      of cancer imaging utilizes computed tomography, where contrast enhancement
      characteristics of lesions can be exploited and detection of subtle lesions can
      involve manipulation of window width and level settings, multiplanar
      reconstruction, and maximum intensity projections. For magnetic resonance
      imaging, diffusion-weighted imaging can render lesions more conspicuous, improve
      characterization, and help assess therapeutic response. Positron emission
      tomography with (18)F-labeled fluorodeoxyglucose and sodium fluoride are
      invaluable in detecting occult existing and new cancerous lesions, characterizing
      indeterminate lesions, and assessing treatment effects. The most common anatomic
      "hiding places" for cancer include metastases to solid organs, such as the
      kidneys and pancreas, gastrointestinal tract, peritoneum and retroperitoneum,
      neural axis, muscular body wall, and bones. Consistent work habits, employment of
      appropriate technologies, and particular attention to the above anatomic areas
      can enhance detection, staging, and reassessments of these complex and often
      stealthy diseases, ensuring the radiologists' integral role in the cancer care
      team.

PMID- 22875477
TI  - Kinetic effects on the interactions of Rh(III) with humic acids as determined
      using size-exclusion chromatography (SEC).
AB  - The anthropogenic inputs of Rh in the environment-together with other platinum
      group elements-have increased considerably during the last 20-30 years. However,
      thermodynamics and kinetics on the interaction of Rh with natural organic and
      inorganic ligands are still poorly characterized. Here, we report the time
      dependent speciation of rhodium chlorides spiked to model freshwater with and
      without the presence of humic substances. Rhodium species were determined using
      size-exclusion chromatography-inductively coupled plasma mass spectrometry (SEC
      ICP-MS). Results indicate that organic matter can effectively bind rhodium, but
      the extremely slow reaction kinetics of Rh plays a significant role on its
      speciation in natural waters. Accordingly, formation of Rh-organic complexes from
      spiked rhodium chlorides required around 15 days to reach equilibrium; this
      should be taken into account in those laboratory experiments where the biological
      interactions of Rh, using spiked samples, are studied. Regarding Rh inorganic
      speciation in freshwater, the available thermodynamic constants predict the
      dominance of the neutral trihydroxo and negatively charged tetrahydroxo rhodium
      complexes over typical pHs (6-8); our results, however, indicate only the
      presence of negatively charged hydroxocomplexes at pH 7. Reexamination of the Rh
      stability constants suggest that these hydroxylated rhodium complexes may also
      dominate its inorganic speciation in seawater.

PMID- 22875478
TI  - Thyroid function testing.

PMID- 22875479
TI  - Hyperglycaemia in inpatients with type 2  diabetes mellitus.

PMID- 22875480
TI  - Nanowear of salivary films vs. substratum wettability.
AB  - The pellicle serves as a multifunctional protective layer, providing, e.g.,
      lubrication and remineralization and also acting as a diffusion barrier. In
      addition, since the formation of the pellicle precedes the adhesion of micro
      organisms, it is also important as a conditioning film. We present a novel
      approach to study the influence of the water wettability of solid surfaces on the
      strength of adsorbed salivary films. It is based on studying the wear resistance
      of the films with an atomic force microscope operated in the friction force
      spectroscopy mode. This methodology provides the strength of the films in terms
      of the forces needed for breaking and removing them. Our results indicate that
      these forces are highly dependent on the water wettability of the underlying
      substrata, decreasing with increasing hydrophobicity. Thus, this study provides
      valuable information for the design of materials exposed in the oral cavity,
      i.e., materials that will minimize plaque formation and be easy to clean.

PMID- 22875482
TI  - Adsorption of fibronectin, fibrinogen, and albumin on TiO2: time-resolved
      kinetics, structural changes, and competition study.
AB  - An understanding of protein adsorption process is crucial for designing
      biomaterial surfaces. In this work, with the use of a quartz-crystal microbalance
      with dissipation monitoring, we researched the following: (a) the kinetics of
      adsorption on TiO(2) surfaces of three extensively described proteins that are
      relevant for metallic implant integration [i.e., albumin (BSA), fibrinogen (Fbg),
      and fibronectin (Fn)]; and (b) the competition of those proteins for adsorbing on
      TiO(2) in a two-step experiment consisted of sequentially exposing the surfaces
      to different monoprotein solutions. Each protein showed a different process of
      adsorption and properties of the adlayer-calculated using the Voigt model. The
      competition experiments showed that BSA displaced larger proteins such as Fn and
      Fbg when BSA was introduced as the second protein in the system, whereas the
      larger proteins laid on top of BSA forming an adsorbed protein bi-layer when
      those were introduced secondly in the system.

PMID- 22875481
TI  - Inhibition of calcineurin in the prefrontal cortex induced depressive-like
      behavior through mTOR signaling pathway.
AB  - RATIONAL: Although it has been recognized that inhibition of calcineurin induced
      depressive-like behavior, the underlying neural mediators have not yet been
      identified. Mammalian target of rapamycin (mTOR), a serine/threonine protein
      kinase that regulates protein synthesis in synapses, has been demonstrated to be
      involved in the rapid antidepressant effects of ketamine. OBJECTIVE: To
      investigate a potential role of mTOR signaling pathway which interferes with
      depressive-like behavior induced by calcineurin blockade and to determine the
      neurobiological mechanisms underlying mood-related disorders. METHODS:
      Calcineurin inhibitor cyclosporine A (CsA) and tacrolimus (FK506) were
      microinjected into the medial prefrontal cortex (mPFC) in rats, and the
      depressive-like behavior was measured in sucrose preference test and forced swim
      test. Additionally, mTOR activity was tested by the levels of phosphorylation of
      p70s6 kinase (p70s6k) and 40S ribosomal protein S6 (rps6). RESULTS: Chronic
      microinjection of CsA or FK506 into mPFC increased depressive-like behaviors and
      decreased mTOR activity, but acute CsA or FK506 had no effects on both behavioral
      phenotype and mTOR activity. Furthermore, activation of mTOR by NMDA reversed the
      depressive-like behavior induced by chronic CsA or FK506 administration.
      Moreover, inhibition of mTOR by rapamycin reversed the antidepressant effects of
      ketamine. Finally, traditional antidepressant venlafaxine prevented the
      depressive-like performance induced by chronic CsA or FK506 treatment.
      CONCLUSION: These findings indicate that calcineurin-inhibition-induced
      depressive-like behavior is mediated by blockade of the mTOR signaling pathway
      and raise the possibility that stimulation of specific brain mTOR may be
      sufficient to decrease risk of affective disorders in patients treated with
      calcineurin inhibitor.

PMID- 22875483
TI  - Identification of a novel ANKK1 and other dopaminergic (DRD2 and DBH) gene
      variants in migraine susceptibility.
AB  - The dopaminergic system plays an important role in migraine and its clinical
      subtypes. Hypersensitization of dopamine receptor type 2 (DRD2) in migraine led
      to successful administration of receptor antagonists in antimigraine therapy.
      Ankyrin repeats and kinase domain containing 1 (ANKK1) gene in DRD2 loci is
      linked to comorbid neurological disorders. Dopamine beta hydroxylase (DBH) is
      responsible for maintaining dopamine-to-norepinephrine ratio implicated in
      migraine pathophysiology. Therefore, we aimed to look for association of
      functional variants in ANKK1 (rs1800497), DRD2 (rs6275 and rs1799732) and DBH
      (rs7239728 and rs1611115) genes with migraine susceptibility. The present study
      was carried out in two dependent cohorts (n primary = 208, n secondary = 127, n
      controls = 200). The results of the cohorts were pooled by meta-analysis using
      Fisher's and Mantel-Haenszel test. Benjamini-Hochberg false discovery rate test
      was used to correct for multiple comparisons. Computer algorithm-based TANGO,
      WALTZ and LIMBO predictions were used to evaluate the effect of missense
      polymorphism (rs1800497). For ANKK1 polymorphism, variant genotype and allele
      showed significant associations with migraine risk. A significant protective
      effect of variant DRD2 rs6275 polymorphism was noticed. DBH rs7239728 imparted
      significant risk at genotypic, allelic and carrier analyses. We identified a risk
      haplotype in DRD2 loci. Two genotype interactions between ANKK1rs1800497 and
      DBHrs72393728 polymorphisms showed significant risks. The variant gene product of
      ANKK1 rs1800497 was predicted with decreased aggregation of ANKK1 protein. In
      conclusion, we identified novel genetic variants, haplotype and gene interactions
      in dopaminergic pathway as potential risk factors for migraine susceptibility.

PMID- 22875484
TI  - Fatigue performance of angle-stable tibial nail interlocking screws.
AB  - PURPOSE: Tibial nail interlocking screw failure often occurs during delayed
      fracture consolidation or at early weight bearing of nailed unstable fractures,
      in general when high implant stress could not be reduced by other means. Is there
      a biomechanical improvement in long-term performance of angle stable locking
      screws compared to conventional locking screws for distal locking of
      intramedullary tibial nails? METHODS: Surrogate bones of human tibiae were cut in
      the distal third and distal locking of the 10 mm intramedullary tibial nail was
      performed with either two angle stable locking screws or two conventional locking
      screws in the mediolateral plane. Six specimens per group were mechanically
      tested under quasi-static and cyclic axial loading with constantly increasing
      force. RESULTS: Angle stable locking screw constructs exhibited significantly
      higher stiffness values (7,809 N/mm +/- 647, mean +/- SD) than conventional
      locking screw constructs (6,614 N/mm +/- 859, p = 0.025). Angle stable locking
      screw constructs provided a longer fatigue life, expressed in a significantly
      higher number of cycles to failure (187,200 +/- 18,100) compared to conventional
      locking screw constructs (128,700 +/- 7,000, p = 0.004). CONCLUSION: Fatigue
      performance of locking screws can be ameliorated by the use of angle stable
      locking screws, being especially important if the nail acts as load carrier and
      an improved stability during fracture healing is needed.

PMID- 22875485
TI  - Deep cavitand vesicles--multicompartmental hosts.
AB  - The synthesis and characterization of vesicles assembled from deep cavitands in
      water is reported. These vesicles act as hosts for three different types of
      guests: the cavitands bind small guest molecules, the bilayer attracts larger
      hydrophobic guests and the inner aqueous compartment contains hydrophilic
      molecules.

PMID- 22875486
TI  - Can parathyroid hormone be used as a biomarker for heart failure?
AB  - Secondary hyperparathyroidism in heart failure is a consequence of renin
      angiotensin-aldosterone activation, chronic hyperaldosteronism, and loop diuretic
      usage, resulting in calcium excretion. The result is an inflammatory state with
      adverse effects on myocardial remodeling and systemic complications. Recent
      literature has suggested that elevated parathyroid hormone predicts adverse
      outcomes in patients with heart failure independent of serum calcium and
      phosphate, vitamin D deficiency, and renal insufficiency. Parathyroid hormone has
      been correlated with elevated brain natriuretic peptide levels, an established
      biomarker of heart failure severity. There are several limitations to the
      utilization of parathyroid hormone as a biomarker for heart failure, and further
      prospective studies need to be conducted to assess the value of multiple
      parathyroid hormone measurements over time and elucidate the role of parathyroid
      hormone in diastolic dysfunction. Pending further validation, there is promise
      for parathyroid hormone as a complementary biomarker in heart failure.

PMID- 22875487
TI  - Efficacy of biologic therapy in patients with chronic pouchitis.

PMID- 22875488
TI  - Letter to the Editor concerning "Gene expression analysis in chronic
      postradiation proctopathy" by Traub et al. (Int J Colorectal Dis 27:879-884,
      2012).

PMID- 22875490
TI  - [Early prenatal genetic diagnosis of oculocutaneous albinism type I in seven
      families].
AB  - OBJECTIVE: To evaluate the feasibility of genetic analysis of tyrosinase gene
      (TYR) in oculocutaneous albinism type I (OCA1). Mutation analysis and prenatal
      genetic diagnosis of TYR gene for seven pedigrees with OCA1 were performed.
      METHODS: PCR was used to amplify the exons, exon-intron boundaries and promoter
      of the TYR gene in the probands and/or their parents. The products were further
      analyzed by direct sequencing. Prenatal genetic diagnoses were performed by
      chorionic villus sampling after the genotypes of the probands or their parents
      were determined. RESULTS: Compound heterozygous mutations were detected in all
      pedigrees, which included 9 mutations, namely R76Q, c.232insGGG, R116X, R278X,
      R299H, c.929-930insC, IVS2-11delTT, Q399X and W400L. Among these, R76Q and Q399X
      were identified for the first time. Seven families have requested prenatal
      diagnoses. One fetus was detected with double mutations of TYR gene, and the
      parents have decided to have therapeutic abortion. Two fetuses did not carry the
      mutations identified in the probands, whilst other four fetuses were carriers of
      heterozygous mutations. Six families decided to carry on with the pregnancies.
      And the neonates did not show any symptoms of OCA after birth. CONCLUSION: Direct
      sequencing of the TYR gene is helpful for genetic counseling, prenatal diagnosis
      and carriers screening of OCA1.

PMID- 22875491
TI  - [Characterization of two Chinese families with aminoglycoside-induced and
      nonsyndromic hearing loss both carrying a mitochondrial 12S rRNA 1494C>T
      mutation].
AB  - OBJECTIVE: To evaluate the effect of mitochondrial DNA(mtDNA) secondary
      mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and
      to study the molecular pathogenic mechanism of maternally transmitted
      aminoglycoside-induced and nonsyndromic hearing loss. METHODS: Two Chinese Han
      pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic
      hearing loss were collected. The two probands and their family members underwent
      clinical, genetic and molecular evaluations including audiological examinations
      and mutational analysis of mitochondrial genome and GJB2 gene. RESULTS: Clinical
      evaluation revealed wide range of severity, age-at-onset and audiometric
      configuration of hearing impairment in matrilineal relatives in both families,
      for which the penetrance of hearing loss was respectively 42.9% and 28.6% when
      aminoglycoside-induced deafness was included. When the effect of aminoglycosides
      was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence
      analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation,
      in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian
      haplogroups C4a1a and B4b1c, respectively. CONCLUSION: Mitochondrial 12S rRNA
      1494C>T mutation probably underlie the deafness in both families. Lack of
      significant mutation in the GJB2 gene ruled out involvement of GJB2 in the
      phenotypic expression. However, aminoglycosides and other nuclear modifier genes
      may still modify the phenotype of the 1494C>T mutation in these families. The
      B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic
      hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to
      have occurred sporadically through evolution.

PMID- 22875492
TI  - [Analysis of GJB2 gene and mitochondrial DNA A1555G mutations in 16 families with
      non-syndromic hearing loss].
AB  - OBJECTIVE: To screen for genetic mutations in families featuring non-syndromic
      hearing loss. METHODS: Sixteen families with non-syndromic hearing loss were
      interviewed to identify medical histories by a questionnaire. Audiological and
      neurological examinations were conducted for all families. Coding regions of GJB2
      and 12S rRNA genes were amplified and sequenced. RESULTS: Of the 17 patients with
      sensorineural hearing loss, 3 were homozygous mutation for GJB2 235 delC, 1 was
      235 delC heterozygous mutation, 1 was 235 delC+299_300 delAT compound
      heterozygous mutation, and 6 were 79G>A+341G>A heterozygosis in cis mutation. No
      1555A>G mutation of mitochondrial DNA (mtDNA) was found in the 16 families.
      CONCLUSION: The incidence of mtDNA 12S rRNA 1555A>G mutation in Jiangsu province
      may be lower than the average across China. Mutations of GJB2 genes may account
      for as much as 64.7% of non-syndromic hearing loss in this study. Screening for
      such mutations and genetic counseling may play an important role in the
      prevention of hereditary hearing loss.

PMID- 22875493
TI  - [Spectral karyotyping of seven prenatally detected marker chromosomes and complex
      chromosome aberrations].
AB  - OBJECTIVE: To perform spectral karyotyping (SKY), fluorescence in situ
      hybridization (FISH) and conventional karyotyping on prenatally detected marker
      chromosomes and complex chromosomal aberrations. METHODS: Five marker chromosomes
      and 2 complex chromosome aberrations diagnosed by G banding were collected. SKY
      was performed to verify the composition of marker chromosomes. FISH was used to
      confirm the diagnosis when necessary. In certain cases, C or N banding technique
      was employed to verify the composition of chromosomes. Results of ultrasonography
      and pregnancy outcome were reviewed. RESULTS: Among the 5 marker chromosomes, 2
      were large and 3 were medium in size, 4 were de novo and one was inherited from
      the father. By SKY analysis, 2 marker chromosomes have originated from non
      acrocentric chromosomes (4 and 9), whilst the other two have originated from
      acrocentric chromosomes (21 and 22). The remainder was derived from X chromosome.
      The SKY results were confirmed by FISH in 3 cases. Four cases have chosen to
      terminate the pregnancy after genetic counseling. A fetus with inherited paternal
      marker chromosome was delivered at term, and showed normal development during the
      first year of life. As for the other 2 cases with complex chromosome aberrations,
      by SKY examination, one had duplication in chromosome 8 and the other had
      chromosome rearrangements derived from translocation between chromosomes 2 and 6.
      In the latter case the fetus was delivered at term but showed developmental
      retardation at 6 months. CONCLUSION: SKY in combination with FISH can facilitate
      identification of the origins of marker chromosomes as well as complex
      chromosomal aberrations. With combined information from ultrasonography, SKY and
      FISH, effective counseling may be offered to the patients.

PMID- 22875494
TI  - [Establishment of an internal control for directed differentiation using
      pluripotent stem cell lines derived from heterozygotic twins].
AB  - OBJECTIVE: To reprogram amniotic fluid cells into pluripotent stem cells in order
      to create an optimal internal control model for directed cell differentiation.
      METHODS: Human amniotic fluid-derived cells (hAFDCs) from heterozygotic twin
      fetuses were induced by retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4.
      In vivo pluripotency, differentiation capacity and karyotype of hAFDCs induced
      pluripotent stem cells (hAFDCs-iPSCs) were determined. RESULTS: hAFDC-iPSCs
      derived from heterozygotic twins have maintained self renewal, with expression of
      high pluripotency marker gene detected at both mRNA and protein levels. The cells
      have maintained their differentiation capacity both in vitro and vivo, and showed
      normal karyotypes after long-term culturing in vitro. CONCLUSION: hAFDCs-iPSCs
      derived from heterozygotic twins have good consistency in terms of genetic
      background, and can provide a good internal control for directed differentiation
      of iPSCs, and may be used an ideal source for autologous cell replacement therapy
      in the later life of the fetus.

PMID- 22875495
TI  - [Molecular genetics and clinical features of nine patients with inherited
      coagulation factor VII deficiency].
AB  - OBJECTIVE: To investigate potential mutations and clinical features of 9
      unrelated patients with inherited coagulation factor VII (FVII) deficiency.
      METHODS: Clinical diagnosis was validated by assaying of coagulation parameters
      including prothrombin time, activated partial thromboplastin time, FVII activity
      and specific antigens. All exons, exon-intron boundaries, and 5' and 3'
      untranslated regions of F7 genes were amplified with PCR. Potential mutations
      were detected by direct sequencing of purified PCR products. Suspected mutations
      were confirmed by sequencing of the opposite strand. RESULTS: All probands have
      featured prolonged prothrombin time, with FVII activity ranging between 2.0% to
      6.0%. The titers of FVII antigen were significantly reduced in 7 probands. Eight
      mutations, including 6 missense mutations, 1 deletion and 1 insertion, were
      identified, among which 3 (Gln100Leu, Ser269Pro and g.11520_11521insT) were not
      described previously. Six mutations have located in the protease domain. All
      mutations were inherited, and consanguineous marriages were reported in 5
      families. Mutations g.27_28delCT, Cys329Gly, Arg304Trp and His348Gln have been
      identified in unrelated families. There was a lack of correlation between the
      mutations and their clinical features. Two individuals with homozygous His348Gln
      mutations and 1 individual with homozygous Arg304Trp mutation were only mildly
      affected or asymptomatic. Two patients, who have respectively carried homozygous
      and heterozygous deletions of g.27_28delCT, were moderately affected and
      asymptomatic. In 4 patients carrying double heterozygous mutations, 1 (Ser269Pro
      and Cys329Gly) was asymptomatic, 2 (Arg304Trp and Cys329Gly, Arg277Cys and
      g.11520_11521insT, respectively) had a mild bleeding tendency, whilst 1
      (Gln100Leu and His348Gln) has a moderate bleeding diathesis. CONCLUSION: There
      seem to be hotspots of F7 gene mutations in ethnic Han Chinese populations. And
      there is a lack of correlation between particular types of mutations and clinical
      phenotypes.

PMID- 22875496
TI  - [Molecular and cytogenetic characterization of six 46, XX males due to
      translocations between the short arms of X and Y chromosomes].
AB  - OBJECTIVE: To characterize molecular and cytogenetic abnormalities in six 46, XX
      males, and to investigate the clinical manifestations and underlying mechanisms
      in such patients. METHODS: Clinical data of six XX male patients were collected.
      Karyotyping, multiple polymerase chain reaction (PCR) and fluorescence in situ
      hybridization (FISH) were utilized to detect and locate the sex determining
      region (SRY) gene. RESULTS: PCR and FISH showed that all patients were SRY
      positive XX males. All patients have their SRY gene located at the tip of
      derivative X chromosomes, which have resulted from translocation between short
      arms of X and Y chromosomes. High resolution karyotyping at 550-750 band level
      has revealed that the translocation breakpoints were at Xp22.33 and Yp11.2 in
      three patients. In the remaining patients, the breakpoints were either at Xp22.32
      and Yp11.31 or Xp22.31 and Yp11.2. The breakpoints at Xp22.32, Xp22.31 and
      Yp11.31 were rarely reported. Genotype-phenotype correlation analysis indicated
      that the clinical manifestations were age-specific. Four adult patients have come
      to clinical attention due to infertility, with typical features including
      azoospermia and testis dysgenesis, whereas poorly developed secondary sexual
      characteristics and short stature were main complaints of adolescence patients,
      and short stature was the sole symptom in a child patient. CONCLUSION: Combined
      karyotyping, PCR and FISH are important for the analysis of XX males.
      Particularly, high resolution karyotyping is valuable for the refinement of
      chromosome breakpoints and detailed analysis of genotype-phenotype correlation.

PMID- 22875497
TI  - [Association between gene polymorphisms and myocardial infarction in Han Chinese
      of Yunnan province].
AB  - OBJECTIVE: To determine frequencies of genetic polymorphisms of coagulation
      factor VII (FVII), coagulation factor FXII (FXII), fibrinogen (FBG) and 9p21 in
      ethnic Han Chinese from Yunnan province, and to assess the association between
      such polymorphisms and onset of myocardial infarction (MI). METHODS: One hundred
      and forty-two patients with MI and 192 healthy controls were analyzed. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      pyrosequencing were used to determine the genotypes of FVII, FXII, FBG and 9p21.
      RESULTS: No significant difference was found in the frequencies of R353Q, 5'F7,
      C46T, -148C/T, rs1333049 and rs4977574 loci between the two groups (P> 0.05).
      However, the frequencies of AA of -455G/A, T and TT of rs1333040, T and TT of
      rs10116277 and G and GG of rs2383207 were significantly higher in MI group
      compared with the controls (P< 0.05), whilst the frequencies of CT of rs1333040
      and GT of rs10116277 were significantly lower in MI group compared with the
      controls (P<0.05). CONCLUSION: Polymorphisms of FVII, FXII, -148C/T of FBG and
      rs1333049 of 9p21 were not associated with myocardial infarction. Polymorphisms
      of -455G/A of FBG and rs1333040, rs10116277 and rs2383207 of 9p21 may be
      associated with MI in ethnic Han Chinese from Yunnan province.

PMID- 22875498
TI  - [Prevalence of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fujian
      Han population].
AB  - OBJECTIVE: To investigate the frequency of CYP2C19 polymorphisms involved in
      clopidogrel metabolism in Fujian Han population. METHODS: Frequencies of CYP2C19*
      2, CYP2C19*3 and CYP2C19*17 in 1001 unrelated Fujian Han volunteers were
      determined with polymerase chain reaction-restriction fragment length
      polymorphism and direct sequencing method. RESULTS: The frequencies of CYP2C19*2,
      *3 and *17 were 32.4%, 5.8% and 0.4%, respectively. According to genotyping
      results, intermediate metabolizers (CYP2C19 *1/*2 or *1/*3) and poor metabolizers
      (CYP2C19 *2/*2 and *2/*3) respectively accounted for 47.95% and 13.99% of all
      subjects. Above frequencies were similar to those of Japan, Korea, Singapore,
      Malaysia, Thailand and Chinese Dai, Mongolian,Li and Hui ethnics (P>0.05), but
      were significantly different from those of Chinese Kazakh and Uygur ethnics, and
      people from Iran, Russia, Italy, Poland, Norway, Canada native Indians, Bolivia,
      Egypt or Tanzania (P<0.05). CONCLUSION: Ethnic/regional diversity exist with
      regard to the prevalence of CYP2C19 polymorphisms. No significant difference were
      found between Fujian Han Chinese and Dai, Mongolian, Li and Hui from China or
      other populations from East and Southeast Asia, but higher frequencies of
      intermediate metabolizers and poor metabolizers compared with populations of
      Kazakh and Uygur in China, and people from Europe, South America and Africa.

PMID- 22875499
TI  - [Functions of carboxyl-terminus of Hsc70 interacting protein and its role in
      neurodegenerative disease].
AB  - Neurodegenerative diseases are a group of chronic progressive neuronal damage
      disorders. The cause is unclear, most of them share a same pathological hallmark
      with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70
      interacting protein (CHIP) is a dual functional molecule, which has a N terminal
      tetratrico peptide repeat (TPR) domain that interacts with Hsc/Hsp70 complex and
      Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U
      box ubiquitin ligase domain that binds to the 26S subunit of the proteasome
      involved in protein degradation via ubiqutin-proteasome system. CHIP protein
      mediates interactions between the chaperone system and the ubiquitin-proteasome
      system, and plays an important role in maintaining the protein homeostasis in
      cells. This article reviews the molecular characteristics and physiological
      functions of CHIP, and its role in cellular metabolism and discusses the
      relationship between CHIP dysfunction and neurodegenerative diseases.

PMID- 22875500
TI  - [Applications and prospect of multiple displacement amplification in
      preimplantation genetic diagnosis].
AB  - Multiple displacement amplification (MDA) is a new technology for whole genome
      amplification (WGA), which can generate large amount of high-quality DNA and
      features high amplification efficiency and fidelity. MDA combined with
      conventional PCR techniques has been successfully applied for preimplantation
      genetic diagnosis, which has broaden latter's clinical applications.

PMID- 22875501
TI  - [Significance of detecting free DNA from maternal plasma for the diagnosis of
      fetal chromosomal aneuploidies].
AB  - OBJECTIVE: To determine the feasibility and accuracy of detecting numerical
      chromosomal abnormalities by high-flux sequencing analysis of free fetal DNA from
      maternal plasma. METHODS: High-flux sequencing was applied to analyze fetal
      chromosome sequence copy numbers in 153 pregnant women. Fetal karyotyping was
      also carried out on amniocentesis samples. RESULTS: Six cases were detected with
      fetal chromosomal abnormalities by high-flux sequencing analysis, among which
      five were confirmed by karyotyping to be chromosomal aneuploidies (47,XYY; 45,X;
      47,XY,+18; 47,XY,+21 and 47,XY,+13), 1 case was confirmed to be structural
      rearrangement, i.e., 46,XY,der(13;21)(q10;q10),+21. Furthermore, 3 chromosomal
      polymorphisms (one 46,XY,21p+ and two 46,XY,Yqh-) were identified. The two
      methods yielded similar results on fetal chromosome copy number detection.
      CONCLUSION: High-flux sequencing analysis of free DNA derived from maternal
      plasma is efficient for detecting fetal chromosomal aneuploidies, and is non
      invasive, highly sensitive and specific. It therefore has a broad application in
      antenatal diagnosis.

PMID- 22875502
TI  - [Array-based comparative genomic hybridization detection of copy number
      variations in a fetus with hypoplastic left-heart syndrome].
AB  - OBJECTIVE: To detect the copy number variations (CNVs) of a fetus with
      hypoplastic left-heart syndrome, and to assess the value of array-based
      comparative genomic hybridization (array-CGH) for molecular cytogenetic
      diagnosis. METHODS: The whole genome of a fetus with normal karyotype by G
      banding was scanned and analyzed by array-CGH, and the CNVs was confirmed by
      multiplex ligation-dependent probe amplification (MLPA). RESULTS: Two
      submicroscopic CNVs [del(11)(q24.1-ter)(121951443-134449216, -12.50
      Mb),dup(15)(q26.3)(96889082-100215359, -3.33 Mb)] were identified and mapped by
      array-CGH. MLPA test confirmed both CNVs. CONCLUSION: Del (11) (q24.1-ter) may
      contribute to hypoplastic left-heart syndrome of the fetus. For its high
      resolution and high-accuracy, array-CGH has provided a powerful tool for
      detection of genomic imbalance.

PMID- 22875503
TI  - [Diagnosis of Down's syndrome using short tandem repeat loci D21S11, D21S1440 and
      Penta D].
AB  - OBJECTIVE: To investigate the feasibility of genetic diagnosis of Down's syndrome
      (DS) using short tandem repeat (STR), and to develop a rapid and accurate method
      for diagnosing DS. METHODS: Quantitative fluorescence polymerase chain reaction
      (QF-PCR) was used to amplify STR loci D21S11, D21S1440 and Penta D of 719
      samples. Three hundred and eighty-nine samples were peripheral blood, 282 were
      amniotic fluid, 48 were chorionic villous samples. The products were analyzed
      using eleterophoresis to detect DS. RESULTS: Among 652 samples with a normal
      karyotype, 635 showed 2 bands with a 1:1 ratio or a single band. The remaining 17
      samples showed 3 bands, and were regarded as false positive results. For 67 DS
      samples, 53 showed 3 bands/peaks with a 1:1:1 ratio and 14 showed 2 bands/peaks
      with a 2:1 ratio. The sensitivity and specificity of STR loci D21S11, D21S1440
      and Penta D were 76.12% and 98.62%, 71.64% and 98.93%, 89.55% and 99.85%,
      respectively. The overall sensitivity and specificity of 3 STR loci were 100%
      (67/67) and 97.39% (635/652), respectively. CONCLUSION: Compared with
      conventional method, author's method is simpler, more stable and rapid, and can
      be used for large-scale prenatal screening of DS.

PMID- 22875504
TI  - [Detection of ED1 gene mutations in six pedigrees with hypohidrotic ectodermal
      dysplasia].
AB  - OBJECTIVE: To identify potential mutations of ED1 gene in six pedigrees with
      hypohidrotic ectodermal dysplasia (HED), and to provide genetic counseling and
      prenatal diagnosis. METHODS: Eight coding exons of ED1 gene of patients with
      clinically diagnosed HED and their relatives were amplified by polymerase chain
      reaction (PCR). The products were further analyzed by direct sequencing. RESULTS:
      Various mutations of ED1 gene were detected, which included R153C, A349T, G299S,
      A349T and X392Q. Heterozygous double peaks at the same position were found in
      female carriers. Deletion of exon 9 was detected in one pedigree. R153C, X392Q
      and deletion of exon 9 were first identified in ethnic Han Chinese. CONCLUSION:
      The identified mutations of ED1 gene may be responsible for the disease. Genetic
      counseling, prenatal diagnosis and carrier screening are now available for these
      families.

PMID- 22875505
TI  - [Clinical investigation of a Chinese family with hypotrichosis simplex of the
      scalp and mutational analysis of CDSN gene].
AB  - OBJECTIVE: To analyze clinical symptoms and disease-causing mutations of
      corneodesmosin (CDSN) gene in a Chinese family affected with hypotrichosis
      simplex of the scalp and to establish a method for prenatal diagnosis. METHODS:
      Family survey and clinical examinations were carried out to determine the
      inheritance pattern. Three patients and 7 unaffected relatives from the family,
      in addition with 100 unrelated healthy controls were recruited. Genomic DNA from
      peripheral blood leukocytes was extracted. Five pairs of primers were designed
      based on the CDSN gene sequence. Exons and flanking regions of the CDSN gene were
      amplified using polymerase chain reaction (PCR). Potential mutations were
      analyzed through direct sequencing and comparison by BLAST. RESULTS: The type of
      alopecia of the family was diagnosed as hypotrichosis simplex of the scalp with
      an autosomal dominant inheritance pattern. A nonsense mutation (C717G) in cDNA
      sequence of the CDSN gene was identified in all three patients of the family,
      which resulted in a premature stop codon (Y239X). The same mutation was not found
      among healthy members of the family and 100 healthy controls. CONCLUSION: A
      Chinese family was diagnosed with hypotrichosis simplex of the scalp, which was
      caused by a novel nonsense mutation (Y239X) in the CDSN gene.

PMID- 22875506
TI  - [Spinal muscular atrophy mimicking myotonic dystrophy: a case report and
      clinical, pathological and genetic analysis].
AB  - OBJECTIVE: To investigate a patient featuring a complex neuromuscular disease
      phenotype. METHODS: A comprehensive analysis integrating clinical investigation,
      electrophysiological testing, pathological analysis and mutation screening was
      carried out. RESULTS: The patient has presented clinical and pathological
      manifestations mimicking Duchenne muscular dystrophy. However, genetic analysis
      has identified no deletion in 21 exons of Dystrophin gene, no pathologic
      expansion of CTG repeats in DMPK gene or CCTG repeats in ZFN9 gene. Instead, a
      homozygous deletion of exons 7 and 8 in SMN gene was discovered. CONCLUSION: A
      rare case of spinal muscular atrophy (SMA) was verified by genetic diagnosis. SMA
      is a group of neuromuscular disorders with great phenotypic heterogeneity and
      sometimes cannot be diagnosed by clinical manifestations, electrophysiological
      and pathological changes alone. Genetic diagnosis has become indispensable for
      accurate diagnosis for patients suspected to have the disease.

PMID- 22875507
TI  - [Association study of NOS1 gene polymorphisms and schizophrenia].
AB  - OBJECTIVE: To assess the association between nitric oxide synthase 1 (NOS1) gene
      polymorphisms and schizophrenia. METHODS: Twenty eight tag single nucleotide
      polymorphisms (SNPs) of NOS1 in 382 schizophrenic patients and 448 healthy
      individuals sampled from Chinese Han population were analyzed by a Illumina
      GoldenGate Genotyping Assay. RESULTS: One SNP (rs1520811) was found to be
      associated with schizophrenia, which however becomes negative after Bonferroni
      correction (P>0.05). Further analysis has failed to identify any association
      between particular haplotypes and the disease. CONCLUSION: Our results did not
      support a significant association between NOS1 gene polymorphisms and
      schizophrenia.

PMID- 22875508
TI  - [Association between parental MTHFR gene polymorphism 677C/T and nonsyndromic
      cleft lip and palate in offspring].
AB  - OBJECTIVE: To explore the association between parental genetic polymorphism of
      methylenetetrahydrofolate reductase (MTHFR) 677C/T and occurrence of nonsyndromic
      cleft lip with or without cleft palate (NSCL/P) in offspring in Shandong
      Province. METHODS: MTHFR genotypes were determined by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). Parents of 89 NSCL/P
      patients treated at Qilu Hospital from August, 2006 to August, 2008 and those of
      64 healthy children were recruited in this case-control study. RESULTS:
      Frequencies of T and C alleles in mothers of patients and healthy children were
      65.73% and 46.09%, and 34.27% and 53.91%, respectively (Chi-square=13.663,
      P<0.01). Offspring whose mothers had T alleles were 2.243 times more likely to
      develop NSCL/P (95%CI: 1.408-3.572). Frequencies of T and C alleles in fathers of
      patients and healthy children were 62.92% and 55.47%, and 37.08% and 44.53%,
      respectively (Chi-square=2.222, P>0.05). The chance for parents of the patient
      and control groups to bear an affected fetus carrying homozygous mutations were
      43% and 29%, respectively (P>0.05). CONCLUSION: In Shandong Province, maternal
      genotype for the MTHFR 677C/T polymorphism has a significant impact on the
      occurrence of NSCL/P in their offspring, whilst paternal genotype for this
      polymorphism may not be a risk factor for NSCL/P in their offspring.

PMID- 22875509
TI  - [The value of 5-HTT gene polymorphism for the assessment and prediction of male
      adolescence violence].
AB  - OBJECTIVE: To establish an adolescent violence crime prediction model, and to
      assess the value of serotonin transporter (5-HTT) gene polymorphism for the
      assessment and prediction of violent crime. METHODS: Investigative tools were
      used to analyze the difference in personality dimensions, social support, coping
      styles, aggressiveness, impulsivity, and family condition scale between 223
      adolescents with violence behavior and 148 adolescents without violence behavior.
      The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was
      compared between the two groups. The role of 5-HTT gene polymorphism on
      adolescent personality, impulsion and aggression scale also was also analyzed.
      Stepwise logistic regression was used to establish a predictive model for
      adolescent violent crime. RESULTS: Significant difference was found between the
      violence group and the control group on multiple dimensions of psychology and
      environment scales. However, no statistical difference was found with regard to
      the 5-HTT genotypes and alleles between adolescents with violent behaviors and
      normal controls. The rate of prediction accuracy was not significantly improved
      when 5-HTT gene polymorphism was taken into the model. CONCLUSION: The violent
      crime of adolescents was closely related with social and environmental factors.
      No association was found between 5-HTT polymorphisms and adolescent violence
      criminal behavior.

PMID- 22875510
TI  - [Association between leptin gene promoter methylation and type 2 diabetes
      mellitus].
AB  - OBJECTIVE: To assess the association between leptin gene promoter methylation and
      serum leptin concentrations in patients with impaired glucose regulation (IGR)
      and type 2 diabetes mellitus (T2DM). METHODS: Methylation status of leptin gene
      promoter was determined with methylation-specific polymerase chain reaction.
      Serum leptin concentrations were determined using enzyme-linked immunosorbent
      assay. RESULTS: Among three groups of individuals with different levels of
      glucose, the methylation rates of leptin gene in IGR and T2DM groups were 43.6 %
      and 31.5 %, respectively, which were significantly lower than that of healthy
      subjects (59.2%; Chi-square=22.499 and 5.109, respectively, P<0.05). A lower
      methylation rate was also observed in T2DM group compared with IGR group (Chi
      square=3.962, P<0.05). Leptin levels in both T2DM and IGR groups were elevated
      compared with normoglycemic subjects, but only T2DM group was significantly
      higher (q=6.81, P<0.01). Linear regression analysis indicated that serum leptin
      concentrations has increased along with declining of DNA methylation rate (r=
      0.95, P<0.01). CONCLUSION: Lower levels of leptin gene promoter DNA methylation
      and serum leptin concentrations are associated with the development of diabetes.
      Measurement of the methylation status of leptin gene promoter and expression can
      facilitate early intervention of the disease.

PMID- 22875511
TI  - [Impact of proton pump inhibitor omeprazole on the antiplatelet effect of
      clopidogrel in individuals with various CYP2C19*2 genotypes].
AB  - OBJECTIVE: To investigate the impact of omeprazole on platelet response to
      clopidogrel and the effect of polymorphisms of CYP2C19 on the antiplatelet effect
      of clopidogrel. METHODS: Platelet aggregation (PA) was assessed before 300 mg
      aspirin plus 300 mg loading dose of clopidogrel and after 300 mg aspirin plus 75
      mg maintenance dose of clopidogrel 7 days later in 414 patients with acute
      coronary syndrome who have undergone percutaneous coronary intervention (PCI).
      Thereafter, gastric mucosal protective drugs were given (omeprazolem 20 mg, n=224
      or cimetidine 800 mg, n=190). Fourteen days later, PA was measured again.
      Genotypes of CYP2C19*2 were analyzed with polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: After taken aspirin and
      clopidogrel, PA has decreased significantly in both groups. Compared with
      cimetidine, omeprazole had no significant impact on PA on 7 and 21 days post PCI.
      Compared with homozygotes or heterozygotes for the wild-type CYP2C19*2, patients
      with CYP2C19*2 AA genotype had significantly higher PA on 7 and 21 days post PCI
      (P<0.05). CONCLUSION: No attenuating effect on platelet response to clopidogrel
      has been observed for Omeprazole. The variant of CYP2C19*2 AA genotype is
      significantly associated with attenuated response to clopidogrel.

PMID- 22875512
TI  - [A Bw12 blood type caused by 278C>T mutation of ABO gene].
AB  - OBJECTIVE: To determine the serotype and genotype of a sample with ABO blood
      group discrepancies. METHODS: Serotype was determined with serological method.
      Sequence specific primer polymerase chain reaction (SSP-PCR) was carried out
      based on the serotype. Sequences of exons 6 and 7 of ABO gene was analyzed by
      sequence-based testing (SBT). RESULTS: Completely agglutinated A antigen, half
      agglutinated B antigen and weak agglutinated anti-B antibody were detected in
      both erythrocytes and serum, which suggested presence of a ABw serotype. An
      A/Bw12 genotype was revealed by B subgroup detection. Sequences of exons 6 and 7
      were 278CT, 297GA and 467CT, 526CG, 657CT, 703GA, 796CA, 803GC, 930GA,
      respectively. The genotype fit with A102/B101 except for a nt278 C>T mutation.
      Blood group antigen gene mutation database (BGMUT) search has confirmed the
      mutant allele to be Bw12. CONCLUSION: An A102/Bw12 genotype has been found in the
      Chinese population.

PMID- 22875513
TI  - [Detection and preliminary study of a family carrying a  CCR5Delta32 deletional
      mutation].
AB  - OBJECTIVE: To investigate the frequencies of chemokine (C-C motif) receptor 5
      gene (CCR5)Delta32 deletional mutation of in Han and Dai populations from Yunnan
      province. Immortalized cell lines were derived from a family carrying the
      CCR5Delta32 mutation. METHODS: Blood samples of 346 Han and 355 Dai individuals
      were collected for genotyping. The coding regions of CCR5 gene were amplified
      with PCR followed by agarose gel electrophoresis. Suspected mutations were
      verified with DNA sequencing. Immortalized cell lines were constructed by using
      Epstain Barr virus and cyclosporine A. The difference between the cell lines and
      original blood samples was verified with PCR. RESULTS: One ethnic Han individual
      was confirmed to be heterozygous for a deletional mutation by sequencing, which
      has led to discovery of a family with CCR5Delta32. Nine immortalized cell lines
      were established from this family, and no difference between the cell lines and
      original blood samples was detected by PCR. CONCLUSION: Together with previous
      reports, this study has indicated a significant difference in CCR5Delta32 among
      different ethnic groups in China. Established immortalized cell lines can also
      provide material for future research.

PMID- 22875515
TI  - Acute renal failure caused by severe coagulopathy induced by the interaction
      between warfarin potassium and levofloxacin: a case report.

PMID- 22875516
TI  - Protecting children and young people: the responsibilities of all doctors.

PMID- 22875517
TI  - The iPad in portable imaging:  radiology on the move.

PMID- 22875519
TI  - Clostridium histolyticum collagenase in the treatment of Dupuytren's contracture.
AB  - Dupuytren's disease is a common, costly and recurrent health issue. This review
      compares Clostridium histolyticum collagenase with current operative treatments.
      Collagenase management is an effective non-surgical alternative associated with
      lower risks of serious adverse events, but higher incidence of non-serious
      adverse events.

PMID- 22875520
TI  - Paraoesophageal hernia: an overview.
AB  - Paraoesophageal hernias are a rare but clinically important type of hiatus
      hernia. Gastric volvulus and perforation may ensue. Investigation and management
      is determined by patient presentation.  This review summarizes current research
      regarding paraoesophageal hernias.

PMID- 22875521
TI  - Posterior tibial tendon dysfunction:  a silent but disabling condition.
AB  - Posterior tibial tendon dysfunction is common and a major cause of flat foot (pes
      planus) and functional impairment in adults. It is frequently undiagnosed and
      therefore inappropriately managed. This review raises awareness of posterior
      tibial tendon dysfunction with the intention of improving patient management.

PMID- 22875522
TI  - Communication in early pregnancy ultrasound: avoiding misunderstandings.
AB  - Pregnant women in the UK are usually offered at least two ultrasound scans during
      their pregnancy. While these almost certainly cause no physical harm to the baby,
      communicating the findings to the parents, whether there is a problem or not,
      carries real potential for confusion, worry and perhaps unnecessary intervention.

PMID- 22875523
TI  - Diabetic gastroparesis: pathophysiology, evaluation and management.
AB  - As the incidence of diabetes mellitus inexorably rises, the burden of its
      complications is becoming increasingly problematic. Among the most bothersome,
      but often under-recognized, inadequately investigated and poorly managed, is
      diabetic gastroparesis.

PMID- 22875524
TI  - Echocardiography and  the non-cardiac anaesthetist.
AB  - Echocardiography is destined to revolutionize perioperative and intensive care
      medicine, as it has already in cardiac anaesthesia. This article reviews the
      evidence underlining why now is the time for general anaesthetists to get
      involved in this rapidly evolving field.

PMID- 22875525
TI  - Sir Leonard Rogers: pioneer in tropical diseases.

PMID- 22875526
TI  - A multidisciplinary team approach to weaning from prolonged mechanical
      ventilation.
AB  - OBJECTIVE: To establish whether multidisciplinary team-led strategies to maintain
      continuity across the weaning process result in an increase in the proportion of
      patients surviving prolonged mechanical ventilation and reduce the length of time
      patients are ventilated. DESIGN: A quality improvement programme was conceived
      and implemented for patients receiving mechanical ventilation for >21 days.
      SETTING: University teaching hospital general intensive care unit. INTERVENTIONS:
      The introduction of long-term weaning plans. MEASUREMENTS AND MAIN RESULTS:
      Intensive care unit survival odds ratio and 95% confidence interval. 0.181 (0.06
      0.49) P<0.01 and hospital survival odds ratio and 95% confidence interval 0.2
      (0.08-0.61) P<0.01, Duration of mechanical ventilation (median 95@ confidence
      interval ) 53 days (32-37) vs 43 days (39-44) P=0.03. CONCLUSION: Long-term
      weaning plans led by a multidisciplinary, team were associated with a reduction
      in intensive care unit and hospital mortality, and duration of mechanical
      ventilation in patients ventilated for >= 21 days. Strategies to maintain
      continuity in this patient parent group are likely fundamental to improving
      outcome.

PMID- 22875527
TI  - Chorea and seizures in iatrogenic hypocalcaemia caused by accidental
      parathyroidectomy.

PMID- 22875528
TI  - N-methyl-D-aspartate receptor  antibody-mediated encephalitis.

PMID- 22875529
TI  - Spontaneous steinstrasse  from multiple ureteric calculi.

PMID- 22875530
TI  - Using property to build your investments.

PMID- 22875532
TI  - Should videolaryngoscopes be used  in difficult airways?

PMID- 22875534
TI  - Acromegaly.

PMID- 22875536
TI  - PcarnBase: development of a transcriptomic database for the brain coral Platygyra
      carnosus.
AB  - The aims of this study were to sequence the transcriptome and organize the
      sequence data into a searchable database for the brain coral Platygyra carnosus,
      a structure-forming dominant species along the coast of southern China. We
      collected healthy and tumorous coral tissues from two locations, extracted RNA
      from each tissue sample, pooled the RNA from all tissue samples, generated a cDNA
      library from the pooled samples, and conducted paired-end sequencing of the cDNA
      library using the Illumina platform to produce 59.6 M clean sequences with a read
      length of 90 bp. De novo assembly of the sequence data resulted in 162,468
      unigenes with an average length of 606 bp (range, 201 to 23,923 bp). This is the
      largest transcriptome dataset for a species of coral whose genome has not been
      sequenced. A BLASTx search against the NCBI protein database showed that 55,355
      of the unigenes matched at least a sequence with an E-value of < 0.00001; 59 % of
      the matched sequences are from Metazoa, 13 % are from Alveolata to which the
      symbiont Symbiodinium belongs, and 7 % are from bacteria. A database (PcarnBase)
      was constructed to provide easy access to the unigenes with attributes such as
      NCBI protein annotation, GO annotation, and KEGG pathway. It will facilitate
      functional genomic studies of P. carnosus, such as biomarker discovery for
      bleaching, tumor formation, and disease development at the gene or protein level,
      involvement of coral symbiotic algae in the host coral's stress responses, and
      genetic basis of stress resistance.

PMID- 22875535
TI  - Organic cation transporters OCT1 and OCT2 determine the accumulation of
      lamivudine in CD4 cells of HIV-infected patients.
AB  - PURPOSE: Identifying factors that determine concentrations of antiretroviral
      drugs in CD4 cells are important for improving therapeutic efficacy. Experimental
      models indicate that the nucleoside reverse transcriptase inhibitor lamivudine is
      transported by the organic cation transporters 1 and 2 (OCT1 and OCT2,
      respectively). Here, we tested whether OCT1 and OCT2 contribute to the uptake of
      lamivudine into native CD4 cells of human immunodeficiency virus (HIV)-infected
      individuals. METHODS: CD4 cells obtained by non-activated cell sorting from 35
      individuals with HIV-1 infection were incubated with lamivudine (10 MUM, 30 min),
      and intracellular concentrations of lamivudine and its active metabolite
      lamivudine triphosphate were determined by liquid chromatography tandem mass
      spectrometry. The expression of OCT1 and OCT2 mRNA was measured by quantitative
      real-time polymerase chain reaction (PCR). A model of OCT2-transfected CD4 cells
      was established for mechanistic investigations. RESULTS: Intracellular
      concentrations of lamivudine and its active metabolite lamivudine triphosphate
      showed strong linear correlations with each other and with the CD4 mRNA
      expression of OCT1 and OCT2 (r > 0.80). Coincubation with protease inhibitors
      (ritonavir, nelfinavir) that inhibit OCT1 and OCT2 yielded decreased
      intracellular concentrations of lamivudine and lamivudine triphosphate.
      Incubation of CD4 cells from healthy donors transfected with an OCT2 expression
      vector yielded increased concentrations of lamivudine and lamivudine
      triphosphate. CONCLUSION: Our studies indicate a role of OCT1 and OCT2 for the
      cellular accumulation of lamivudine in HIV-infected individuals.

PMID- 22875537
TI  - Application of MALDI-TOF mass spectrometry for the detection of enterotoxins
      produced by pathogenic strains of the Bacillus cereus group.
AB  - Enterotoxins produced by different species of the Bacillus cereus group, such as
      cytotoxin K1 (CytK1) and non-haemolytic enterotoxin (NHE), have been associated
      with diarrhoeal food poisoning incidents. Detection of CytK1 is not possible with
      commercial assays while NHE is recognised by an immunological kit (TECRA) that
      does not specifically target this protein because it is based on polyclonal
      antibodies. It is evident that the lack of suitable tools for the study of
      enterotoxins hampers the possibilities for accurate hazard identification and
      characterisation in microbial food safety risk assessment. We applied matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI
      TOF/MS) for the detection of CytK1 and NHE produced by pathogenic strains of the
      B. cereus group using protein digests from 1D gel electrophoresis. Secretion of
      CytK1 and two of the three components of NHE was confirmed in supernatants of
      different B. cereus cultures. For each protein, we introduce biomarkers that
      could be used for the screening of food poisoning or food/environmental isolates
      that can secrete enterotoxins. For example, tryptic peptides of 2,310.2 and
      1,192.5 Da (calculated mass) can be indicators for CytK1 and NheA, respectively,
      although a simultaneous detection of other enterotoxin-specific peptides is
      recommended to assure the presence of a toxin in an unknown sample. Comparison of
      MALDI-TOF/MS with the TECRA kit showed that our methodological strategy performed
      well and it had the competitive advantage of specifically detecting NheA.
      Therefore, MALDI-TOF/MS can be successfully incorporated into risk assessment
      procedures in order to determine the involvement of strains of the B. cereus
      group in foodborne outbreaks, including the recently described cytK1 producing
      species, Bacillus cytotoxicus.

PMID- 22875538
TI  - In vitro dose-response effects of poly(amidoamine) dendrimers [amino-terminated
      and surface-modified with N-(2-hydroxydodecyl) groups] and quantitative
      determination by a liquid chromatography-hybrid quadrupole/time-of-flight mass
      spectrometry based method.
AB  - This article presents a dose-response study of the effects of two types of third
      generation (G3) and fourth-generation poly(amidoamine) (PAMAM) dendrimers on two
      cell lines (RTG-2 and H4IIE) by in vitro cytotoxicity assays with 3-(4,5
      dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red uptake
      (NRU), and lactate dehydrogenase (LDH) assays. We particularly investigated the
      potential cytotoxic effect of positive surface charge, which a cationic amino
      terminated PAMAM dendrimer can display, on the marked ability of PAMAM dendrimers
      to cross the cell membrane compared with PAMAM dendrimers functionalized with
      chains of N-(2-hydroxydodecyl). Quantification of dose-response effects was
      performed by use of mass spectrometry analysis. The analytical method using
      liquid chromatography-hybrid quadrupole/time-of-flight mass spectrometry that we
      developed allowed characterization of defective dendrimers instead of "ideal
      structures." Identification was based on accurate mass measurement, assignment of
      elemental composition, and the fully resolved (13)C/(12)C isotopic clusters of
      the multiply charged ions of PAMAM dendrimers. Validation of the liquid
      chromatography-mass spectrometry method made possible reliable and reproducible
      quantification of the extracellular and intracellular concentration of dendrimers
      at a micromolar level (limits of detection from 0.14 to 1.34 MUM and from 0.43 to
      1.82 MUM in standard and culture medium, respectively). A higher cytotoxicity was
      found with the H4IIE cell line for surface-modified PAMAM dendrimers. The LDH
      assay was significantly more sensitive than the MTT and NRU assays, with half
      maximal inhibitory concentrations (IC(50)) of 12.96 and 38.31 MUg mL(-1) for
      surface-modified G3 and G4 dendrimers, respectively. No cytotoxic effects, in
      terms of IC(50), of amino-terminated PAMAM dendrimers were observed on both H4IIE
      and RTG-2 cells when the concentration was below 500 MUg mL(-1) for G3 and G4
      dendrimers.

PMID- 22875539
TI  - Role of molecular mimicry and polyclonal cell activation in the induction of
      pathogenic beta2-glycoprotein I-directed immune response in Balb/c mice upon
      hyperimmunization with tetanus toxoid.
AB  - It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer
      of sera beta2-glycoprotein I (beta2GPI)-specific antibodies (Abs) in Balb/c mice.
      The concentrations of such induced anti-beta2GPI Abs as well as their pathogenic
      potential are strongly influenced by the context of TTd application. beta2GPI
      specific immune response is established as a part of TTd-specific immune response
      by molecular mimicry mechanism due to structural homology between TTd and
      beta2GPI. This finding is supported by the following facts: (1) cross-reactive
      Abs that recognize both TTd and beta2GPI epitopes are present in Balb/c mice
      sera; (2) anti-TTd Abs secretion in splenic cultures is induced after beta2GPI
      stimulation and vice versa. However, analyses of (1) IL-10 production following
      in vitro stimulation of immunized Balb/c mice splenocytes by TTd, beta2GPI or
      glutaraldehyde-treated beta2GPI and (2) specific impact of ConA and agonists of
      TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply
      that these two branches of the TTd-induced immune response do not use identical
      cell populations and are regulated in a different way. Results presented in this
      paper describe that structural homology between foreign and self-antigens could
      focus mounted autoreactive immune response toward specific self-structure, but
      the context of antigen application, including a history of previous immune
      stimulations and adjuvants applied together with the antigen, are the main
      factors which determine the outcome of the induced immune response.

PMID- 22875540
TI  - Can volunteers collect data that are comparable to professional scientists? A
      study of variables used in monitoring the outcomes of ecosystem rehabilitation.
AB  - Having volunteers collect data can be a cost-effective strategy to complement or
      replace those collected by scientists. The quality of these data is essential
      where field-collected data are used to monitor progress against predetermined
      standards because they provide decision makers with confidence that choices they
      make will not cause more harm than good. The integrity of volunteer-collected
      data is often doubted. In this study, we made estimates of seven vegetation
      attributes and a composite measure of six of those seven, to simulate benchmark
      values. These attributes are routinely recorded as part of rehabilitation
      projects in Australia and elsewhere in the world. The degree of agreement in data
      collected by volunteers was compared with those recorded by professional
      scientists. Combined results showed that scientists collected data that was in
      closer agreement with benchmarks than those of volunteers, but when data
      collected by individuals were analyzed, some volunteers collected data that were
      in similar or closer agreement, than scientists. Both groups' estimates were in
      closer agreement for particular attributes than others, suggesting that some
      attributes are more difficult to estimate than others, or that some are more
      subjective than others. There are a number of ways in which higher degrees of
      agreement could be achieved and introducing these will no doubt result in better,
      more effective programs, to monitor rehabilitation activities. Alternatively,
      less subjective measures should be sought when developing monitoring protocols.
      Quality assurance should be part of developing monitoring methods and explicitly
      budgeted for in project planning to prevent misleading declarations of
      rehabilitation success.

PMID- 22875541
TI  - Improving front-end flow in an urban academic medical center emergency
      department: the emergency department discharge facilitator team.
AB  - Length of stay (LOS) is an important determinant of patient satisfaction and
      overall emergency department (ED) operational efficiency. In an effort to reduce
      length of stay for low-acuity "treated and released" patients, our department
      created a discharge facilitator team (DFT) composed of an attending physician,
      physician assistant, and registered nurse. The DFT identified patients who could
      be rapidly treated and released in the low-acuity treatment Adult Urgent Care
      Center (AUCC) and provided them rapid treatment and discharge. To assess the
      efficacy of the DFT, linear regression was used to compare AUCC LOS at times the
      team was and was not active. Patients seen by the DFT had a LOS that was 35 %
      shorter than other AUCC patients. There was a 28-min reduction in AUCC LOS during
      periods where the DFT was active (95% CI 22 to 33 min). We conclude that the
      establishment of a DFT was associated with a significant reduction in LOS for all
      low-acuity patients. Other academic medical centers may consider implementing a
      similar program in order to reduce LOS and improve ED throughput for low acuity
      patients.

PMID- 22875542
TI  - Analysis of the gene expression profile of curcumin-treated kidney on endotoxin
      induced renal inflammation.
AB  - Acute or chronic kidney inflammation is closely related to the progress of kidney
      diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma
      longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The
      present study aimed to investigate the effects and explore the protective
      mechanism of curcumin on lipopolysaccharide (LPS)-induced kidney inflammation in
      mice using gene chip and pathological technology. Nine SPF Kunming mice (aged 6-8
      weeks, weighing 20-25 g) were divided into three groups. Saline and LPS were
      injected intraperitoneally in a normal control group and a model group,
      respectively. Mice in the treatment group were first injected with curcumin (5
      mg/kg) for 3 days before being injected with LPS (5 mg/kg). Kidney tissues were
      harvested at 6 h after treatment. Parts of kidney were fixed with 10 %
      formaldehyde for HE, Periodic acid-Schiff staining, and immunohistochemistry.
      Affymetrix gene chips (mouse 430 chip) were used to detect the renal gene
      expression profile, and the results were analyzed using bioinformatics methods.
      The renal gene expression profile showed that there are 148 Affy IDs (up-down
      group) whose levels of gene expression were increased after LPS stimulation and
      decreased by curcumin treatment and that there are 133 Affy IDs (down-up group)
      exhibiting the opposite trend. In the differentially expressed genes of the up
      down group, 21 Gene Ontology (GO) genes were selected by screening function (P <=
      0.01). In the biological processes, most of the genes were found to be related to
      the genes of regulation of macrophage activation and macrophage activation
      associated genes. In the cellular localization, there were four functional GO
      genes (P <= 0.01); in the molecular structure, there were seven functional GO
      genes (P <= 0.01). In the down-up group, there were functional GO genes (P <=
      0.01) and one functional GO gene (P <= 0.01) in the biological process and the
      cellular localization, respectively. Macrophage infiltration could be observed as
      early as 6 h after LPS stimulation. Pretreatment with 5 mg/kg of curcumin
      significantly decreased the macrophage infiltration. At 6 h after LPS injection,
      significant decreased expression of M6PRBP-1 and NEDD-4 was observed in renal
      tissue. On the other hand, pretreatment with curcumin significantly increased
      renal M6PRBP-1 and NEDD-4 expression. In this study, we also found the signaling
      pathway and the possible target gene of the protective effects of curcumin on
      endotoxin-induced renal inflammation. The kidney gene expression profile in the
      inflammatory state was clarified by using gene chip technology. Furthermore, we
      confirmed that curcumin treatment can change the gene expression profile.

PMID- 22875544
TI  - A vital field.

PMID- 22875543
TI  - Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro
      and in vivo.
AB  - Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti
      cancer properties; however, the anti-inflammatory effects of OA on
      lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been
      studied. Here, we first investigated the possible anti-inflammatory effects of OA
      against pro-inflammatory responses in human umbilical vein endothelial cells
      (HUVECs) induced by LPS and the associated signaling pathways. We found that OA
      inhibited LPS-induced barrier disruption, expression of cell adhesion molecules
      (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also
      suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose
      induced leukocyte migration in vivo. Further studies revealed that OA suppressed
      the production of tumor necrosis factor-alpha and activation of nuclear factor
      kappaB by LPS. Collectively, these results suggest that OA has anti-inflammatory
      effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion
      and migration of leukocytes, thereby endorsing its usefulness as a therapeutic
      agent for vascular inflammatory diseases.

PMID- 22875545
TI  - Mindfulness-based cognitive therapy: benefits in reducing depression following a
      traumatic brain injury.
AB  - CONTEXT: Current therapies for traumatic brain injury (TBI) include
      pharmacotherapy, psychotherapy, and cognitive rehabilitation. Unfortunately,
      psychological and emotional issues regularly go untreated in individuals with TBI
      even after they receive treatment for physical, behavioral, and cognitive issues.
      Mindfulness-based cognitive therapy (MBCT) may offer new rehabilitation
      opportunities for individuals with TBI. OBJECTIVE: To demonstrate the efficacy of
      MBCT in the treatment of clinically diagnosed depression in a TBI population.
      DESIGN: The research team measured depression, pain frequency and intensity,
      energy levels, health status, and function preintervention and postintervention.
      SETTING: The research team conducted the study at the Ottawa Hospital
      Rehabilitation Centre, Ontario, Canada. PARTICIPANTS: The research team recruited
      23 participants from two sources: (1) the brain injury program at the hospital
      and (2) the local head-injury association. Twenty participants completed the
      study. INTERVENTION: The intervention was 8 weeks in length, with a 90-minute
      MBCT session once a week. The research team based the specific content of the
      study's intervention on a combination of Kabat-Zinn's manualized mindfulness
      based stress reduction program and Segal and colleague's manual for MBCT. OUTCOME
      MEASURES: The research team determined statistical significance using paired t
      tests for continuous outcomes and the McNemar chi-square test for dichotomous
      categorical outcomes. They also calculated effect sizes for all depression
      measures. RESULTS: Postintervention, the study found that MBCT significantly
      reduced (P < .050) depression symptoms on all scales compared to baseline. The
      study demonstrated medium to large effect sizes for each depression measure.
      Participants indicated reduced pain intensity (P = .033) and increased energy
      levels (P = .004). No significant changes occurred in anxiety symptoms, pain
      frequency, and level of functioning postintervention. CONCLUSION: MBCT was
      efficacious in reducing depression in the TBI population, providing ample
      rationale for further research with more robust designs. This study marks an
      important step toward the development and provision of MBCT on a wider scale to
      support the rehabilitation efforts of people who have depression symptoms
      following TBI.

PMID- 22875546
TI  - Spirituality, environmental consciousness, and health awareness and use of
      complementary and alternative medicine.
AB  - CONTEXT: Complementary and alternative medicine (CAM) refers to a wide range of
      disease-treating and preventive therapies that are not considered traditional or
      conventional by biomedical standards. Research suggests that CAM use is
      increasing. Understanding lifestyle differences based on level of CAM use may be
      important knowledge for health-care providers. OBJECTIVES: To understand the
      relationship between level of CAM use (high, medium, or low) and three lifestyle
      factors-spirituality (ie, a sense of fulfillment from being spiritual),
      environmental consciousness (ie, a concern for the environment), and health
      awareness (ie, monitoring the nutritional value of food). DESIGN: Participants
      completed the Perspectives on the Use in Communities of CAM questionnaire
      (Robinson et al, 2007), which measures levels of spirituality, environmental
      consciousness, and health awareness among CAM users. Participants also rated
      their frequency of CAM use across a wide array of CAM practices. The authors
      calculated total CAM use by summing the frequency of use of 28 CAM therapies, and
      they grouped individuals into three categories of usage: low (n = 42), medium (n
      = 108), and high (n = 40). They then examined the relationships between the use
      categories and the three lifestyle categories. SETTING: The study occurred at a
      midsized Midwestern university, the University of South Dakota. PARTICIPANTS:
      Participants included 131 female and 59 male college students (young adults).
      OUTCOME MEASURES: The authors performed a multivariate analysis of variance
      (MANOVA) with three dependent variables: spirituality, environmental
      consciousness, and health awareness. The independent variable was level of CAM
      use. RESULTS: MANOVAs indicated significant main effects, suggesting changes in
      lifestyle practices based on level of CAM use, Wilks' Lambda criterion: F(6, 368)
      = 5.54, P < .001, R2 = .16. Follow-up results and planned pairwise comparisons
      suggest that level of CAM use affected all three lifestyle practices. Moreover,
      unexpected results demonstrated that as the level of CAM use increased from
      medium to high, health awareness also increased. All post-hoc tests used
      Bonferroni corrected alpha levels. CONCLUSION: The results suggest that as CAM
      use increases, positive lifestyle factors increase. These findings highlight the
      importance of CAM use as a method of increasing overall health as well as
      improving practitioners' understanding of and ability to assist patients in
      increasing overall well-being through nontraditional or nonconventional means.

PMID- 22875547
TI  - Step climbing capacity in patients with pulmonary hypertension.
AB  - BACKGROUND: Patients with pulmonary hypertension (PH) typically have exercise
      intolerance and limitation in climbing steps. OBJECTIVES: To explore the exercise
      physiology of step climbing in PH patients, on a laboratory-based step test.
      METHODS: We built a step oximetry system from an 'aerobics' step equipped with
      pressure sensors and pulse oximeter linked to a computer. Subjects mounted and
      dismounted from the step until their maximal exercise capacity or 200 steps was
      achieved. Step-count, SpO(2) and heart rate were monitored throughout exercise
      and recovery. We derived indices of exercise performance, desaturation and heart
      rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level
      were measured. Lung function tests and hemodynamic parameters were extracted from
      the medical record. RESULTS: Eighty-six subjects [52 pulmonary arterial
      hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were
      recruited. Exercise performance (climbing time, height gained, velocity, energy
      expenditure, work-rate and climbing index) on the step test was significantly
      worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was
      a good correlation between exercise performance on the step and 6-min walking
      distance-climb index (r = -0.77, p < 0.0001). The saturation deviation (mean of
      SpO(2) values <95 %) on the step test correlated with diffusion capacity of the
      lung (rho = -0.49, p = 0.001). No correlations were found between the step test
      indices and other lung function tests, hemodynamic parameters or NT-proBNP
      levels. CONCLUSIONS: Patients with PAH/CTEPH have significant limitation in step
      climbing ability that correlates with functional class and 6-min walking
      distance. This is a significant impediment to their daily activities.

PMID- 22875548
TI  - Parental control over mate choice to prevent marriages with out-group members: a
      study among mestizos, Mixtecs, and Blacks in Mexico.
AB  - The present research examined how a preference for influencing the mate choice of
      one's offspring is associated with opposition to out-group mating among parents
      from three ethnic groups in the Mexican state of Oaxaca: mestizos (people of
      mixed descent, n = 103), indigenous Mixtecs (n = 65), and blacks (n = 35). Nearly
      all of the men in this study were farmworkers or fishermen. Overall, the level of
      preferred parental influence on mate choice was higher than in Western
      populations, but lower than in Asian populations. Only among the Mixtecs were
      fathers more in favor of parental influence on the mate choice of children than
      mothers were. As predicted, opposition to out-group mating was an important
      predictor of preferred parental influence on mate choice, more so among fathers
      than among mothers, especially in the mestizo group-the group with the highest
      status. In addition, women, and especially mestizo women, expressed more
      opposition to out-group mating than men did.

PMID- 22875549
TI  - Baroreflex sensitivity estimation by the sequence method with delayed signals.
AB  - OBJECTIVE: To evaluate a modified sequence method with delayed time series for
      baroreflex sensitivity (BRS) estimation during supine position and orthostatism
      in healthy human beings. METHODS: Nineteen clinically healthy volunteers (12 men,
      age 28.4 +/- 6.2 years old) were included. Blood pressure recordings were
      obtained during supine position and orthostatism (15 min each) with a Finometer.
      Systolic blood pressure (SBP) and inter beat intervals (IBI) measured from all
      heartbeats were used to estimate BRS in both positive and negative sequences,
      with SBP delayed between 0 and 5 heartbeats. BRS estimations were compared by
      ANOVA, p < 0.05 was considered significant. Optimal recording time based on fixed
      BRS error estimation was calculated for each time series. RESULTS: BRS estimation
      was similar between positive and negative sequences in all conditions (BRS = 12.0
      +/- 2.0 ms/mmHg in supine position, delay 0). BRS with no delay was similar to
      BRS with delays between 1 and 5 heartbeats. Compared to supine position, BRS was
      smaller in orthostatism in all delays (BRS = 8.0 +/- 2.0 ms/mmHg with delay 0).
      The shortest optimal recording time with delayed time series was similar in
      supine position and orthostatism (4.3 +/- 1.7 vs. 3.74 +/- 0.07 min,
      respectively). Estimation error was linearly correlated to IBI, regardless of the
      delay. CONCLUSION: BRS estimation with sequence method improves with delayed time
      series, during supine position and orthostatism. Reduced BRS estimation error and
      recording time from this method could benefit studies with large populations or
      patients with low tolerance to orthostatism.

PMID- 22875550
TI  - Central hyperthermia, brain hyperthermia and low hypothalamus temperature.
AB  - INTRODUCTION, PATIENTS AND METHODS: We measured brain temperature in a case of
      central hyperthermia. RESULTS: Brain temperature was increased except for
      hypothalamus that was colder. CONCLUSION: We suppose that central hyperthermia is
      driven by cold hypothalamus.

PMID- 22875552
TI  - Adherence to the Mediterranean diet pattern has declined in Spanish adults.
AB  - This work examined the Spanish population's degree of accordance with the
      Mediterranean diet (MD). This was a cross-sectional study conducted in 2008-2010
      among 11,742 individuals representative of the Spanish population aged >= 18 y.
      Habitual food consumption was assessed with a computerized diet history.
      Accordance of food consumption with the MD was assessed with the MD Adherence
      Screener (MEDAS) score using the cutoffs >= 9 to define strict accordance and >=
      7 (mid-range value) for modest accordance. Accordance of nutrient intake with the
      MD was defined as >= 4.5 points (mid-range value) on the high-unsaturated fat
      OmniHeart diet score. The diet of 12% (95% CI: 11.3-12.7%) of the Spanish
      population reached MEDAS-based strict accordance with the MD and 46% (95% CI:
      44.7-47.7) attained modest accordance. Moreover, 39.0% (95%: 37.8-40.1%) of the
      population achieved OnmiHeart-based MD accordance. Factor analysis identified 2
      main dietary patterns. The first one was called "Westernized" and was rich in red
      and processed meat, French fries, refined cereals, and sweetened beverages and
      poor in fresh fruit; the second pattern was named "Mediterranean" and was rich in
      olive oil and plant-based foods. Regardless of how it was defined, MD accordance
      was less frequent and the Westernized pattern was more frequent among the
      younger, the less educated, current smokers, and those less physically active and
      more sedentary. In conclusion, the Spanish population is drifting away from the
      MD to adopt a less healthy diet, typical of Western countries. The departure from
      the MD mostly affects the socially disadvantaged and clusters with other
      unhealthy lifestyles, which may have synergistic undesirable effects on health.

PMID- 22875553
TI  - Introduction of beta-carotene-rich orange sweet potato in rural Uganda resulted
      in increased vitamin A intakes among children and women and improved vitamin A
      status among children.
AB  - Vitamin A deficiency (VAD) persists in Uganda and the consumption of beta
      carotene-rich orange sweet potato (OSP) may help to alleviate it. Two large
      scale, 2-y intervention programs were implemented among Ugandan farmer households
      to promote the production and consumption of OSP. The programs differed in their
      inputs during year 2, with one being more intensive (IP) and the other being
      reduced (RP). A randomized, controlled effectiveness study compared the impact of
      the IP and RP with a control on OSP and vitamin A intakes among children aged 6
      35 mo (n = 265) and 3-5 y (n = 578), and women (n = 573), and IP compared with
      control on vitamin A status of 3- to 5-y-old children (n = 891) and women (n =
      939) with serum retinol <1.05 MUmol/L at baseline. The net OSP intake increased
      in both the IP and RP groups (P < 0.01), accounting for 44-60% of vitamin A
      intake at follow-up. The prevalence of inadequate vitamin A intake was reduced in
      the IP and RP groups compared with controls among children 6-35 mo of age (>30
      percentage points) and women (>25 percentage points) (P < 0.01), with no
      differences between the IP and RP groups of children (P = 0.75) or women (P =
      0.17). There was a 9.5 percentage point reduction in prevalence of serum retinol
      <1.05 MUmol/L for children with complete data on confounding factors (n = 396; P
      < 0.05). At follow-up, vitamin A intake from OSP was positively associated with
      vitamin A status (P < 0.05). Introduction of OSP to Ugandan farming households
      increased vitamin A intakes among children and women and was associated with
      improved vitamin A status among children.

PMID- 22875554
TI  - DICOM relay over the cloud.
AB  - PURPOSE: Healthcare institutions worldwide have adopted picture archiving and
      communication system (PACS) for enterprise access to images, relying on Digital
      Imaging Communication in Medicine (DICOM) standards for data exchange. However,
      communication over a wider domain of independent medical institutions is not well
      standardized. A DICOM-compliant bridge was developed for extending and sharing
      DICOM services across healthcare institutions without requiring complex network
      setups or dedicated communication channels. METHODS: A set of DICOM routers
      interconnected through a public cloud infrastructure was implemented to support
      medical image exchange among institutions. Despite the advantages of cloud
      computing, new challenges were encountered regarding data privacy, particularly
      when medical data are transmitted over different domains. To address this issue,
      a solution was introduced by creating a ciphered data channel between the
      entities sharing DICOM services. RESULTS: Two main DICOM services were
      implemented in the bridge: Storage and Query/Retrieve. The performance measures
      demonstrated it is quite simple to exchange information and processes between
      several institutions. The solution can be integrated with any currently installed
      PACS-DICOM infrastructure. This method works transparently with well-known cloud
      service providers. CONCLUSIONS: Cloud computing was introduced to augment
      enterprise PACS by providing standard medical imaging services across different
      institutions, offering communication privacy and enabling creation of wider PACS
      scenarios with suitable technical solutions.

PMID- 22875555
TI  - Advanced care nurse practitioners can safely provide sole resident cover for
      level three patients: impact on outcomes, cost and work patterns in a cardiac
      surgery programme.
AB  - OBJECTIVES: There are significant pressures on resident medical rotas on
      intensive care. We have evaluated the safety and feasibility of nurse
      practitioners (NPs) delivering first-line care on an intensive care unit with all
      doctors becoming non-resident. Previously, resident doctors on a 1:8 full-shift
      rota supported by NPs delivered first-line care to patients after cardiac
      surgery. Subsequently, junior doctors changed to a 1:5 non-resident rota and NPs
      onto a 1:7 full-shift rota provided first-line care. METHODS: A single centre
      before-and-after service evaluation on cardiac intensive care. KEY MEASURES FOR
      IMPROVEMENT: mortality rates, surgical trainee attendance in theatre and cost
      before and after the change. After-hour calls by NPs to doctors and subsequent
      actions were also audited after the change. RESULTS: The overall mortality rates
      in the 12 months before the change were 2.8 and 2.2% in the 12 months after (P =
      0.43). The median [range] logistic EuroSCORE was 5.3 [0.9-84] before and 5.0 [0.9
      85] after the change (P = 0.16). After accounting for the risk profile, the odds
      ratio for death after the change relative to before was 0.83, 95% confidence
      interval 0.41-1.69. Before the change, a surgical trainee attended theatre 467 of
      702 (68%) cases. This increased to 539 of 677 (80%) cases after the change (P <
      0.001). The annual cost of staffing the junior doctor and NP programme before the
      change was L933 344 and L764 691 after. In the year after the change, 192 after
      hour calls were made to doctors. In 57% of cases telephone advice sufficed and
      doctors attended in 43%. CONCLUSIONS: With adequate training and appropriate
      support, resident NPs can provide a safe, sustainable alternative to traditional
      staffing models of cardiac intensive care. Training opportunities for junior
      surgeons increased and costs were reduced.

PMID- 22875556
TI  - Frozen elephant trunk surgery: evolving grafts and techniques.

PMID- 22875557
TI  - An effectiveness study comparing acupuncture, physiotherapy, and their
      combination in poststroke rehabilitation: a multicentered, randomized, controlled
      clinical trial.
AB  - CONTEXT: Stroke is a leading cause of death and disability worldwide, being the
      third leading cause of death in the United States and the second and third most
      common causes of death in Chinese cities and rural areas, respectively.
      Evaluation of different rehabilitative modalities appears necessary to optimize
      treatment. OBJECTIVES: To compare acupuncture and physiotherapy for effectiveness
      and reliability in treating hemiplegic patients after stroke. DESIGN: The
      research team designed a multicentered, three-arm, randomized controlled trial.
      Power calculations revealed a targeted sample size of 310 participants. SETTING:
      The study took place at seven in-patient hospitals in China. PARTICIPANTS: The
      research team screened a total of 310 patients. Of that number, 274 completed the
      study, 15 did not meet the inclusion/exclusion criteria, and 21 dropped out.
      Adverse events were rare (less than 1%), mild, and temporary. INTERVENTION: The
      research team randomly divided participants into three groups that all received
      conventional care as needed-including psychological counseling, standard nursing
      care, and daily medical evaluation plus (1) acupuncture, (2) physiotherapy, or
      (3) acupuncture plus physiotherapy. The participants received treatments once a
      day, 6 days a week for 4 weeks. OUTCOME MEASURES: The research team evaluated all
      patients at baseline, after 2 weeks, and after 4 weeks using the Fugl-Meyer
      Assessment of Physical Performance (FMA), a modified Barthel Index (BI), and the
      Neurologic Defect Scale (NDS). RESULTS: No significant differences existed
      between the three groups at baseline. Compared to baseline, participants in all
      groups improved their FMA, BI, and NDS scores by the end of week 2 (P<=.05) and
      further improved by the end of week 4 (P<=.05) The study found no statistically
      significant differences in outcomes between the three groups after treatment
      (P>.05). CONCLUSION: Acupuncture plus conventional care was similar in
      effectiveness to physiotherapy treatment plus conventional care for poststroke
      rehabilitation. The study found no synergistic effects for the combination of
      acupuncture and physiotherapy in addition to conventional care; that combination
      of treatments was no more effective than either treatment by itself. The
      effectiveness and lack of adverse events associated with acupuncture in this
      study suggest that it may represent an additional treatment option for stroke
      patients.

PMID- 22875558
TI  - Tai chi exercise for patients with heart disease: a systematic review of
      controlled clinical trials.
AB  - CONTEXT: To summarize and evaluate the available evidence from controlled
      clinical trials of tai chi (TC) exercise for patients with heart disease. SEARCH
      METHODS: Fourteen databases were searched up to November 2010 with the terms tai
      chi, taichi, tai ji, taiji, taijichuan, cardiac, heart, coronary, myocardial, and
      atrial fibrillation in the title, abstract, or key words. No language
      restrictions were imposed. The quality and validity of randomized clinical trials
      (RCTs) were evaluated using the Jadad Scale. The strength of the evidence for all
      included studies was evaluated using the Oxford Centre for Evidence-based
      Medicine Levels of Evidence. RESULTS: Nine studies including 5 RCTs and 4
      nonrandomized controlled clinical trials met the inclusion criteria. Three
      studies examined the effectiveness of TC exercise for patients with chronic heart
      failure (CHF), and 6 studies examined the effectiveness of TC exercise among
      patients with coronary heart disease (CHD). Overall, these studies demonstrated
      favorable effects of TC exercise for the patients with heart disease.
      CONCLUSIONS: The existing evidence suggests that TC exercise is a good option for
      heart patients with very limited exercise tolerance and can be an adjunct to
      rehabilitation programs for patients with CHD or CHF.

PMID- 22875559
TI  - Patients' experiences and perceptions of integrative care for back and neck pain.
AB  - CONTEXT: Conventional guidelines in Sweden recommend primary care management for
      back and neck pain, yet these two conditions are the most common ones for which
      patients use complementary therapies. Despite the recent growth of integrative
      medicine (IM) in different clinical, academic, and societal contexts, few studies
      have defined and investigated comprehensive models of integrative care as
      compared to conventional management, especially using randomized clinical trials.
      OBJECTIVE: The study explores patients' experiences and perceptions when
      receiving conventional or integrative care in the management of back and neck
      pain. DESIGN: The research team conducted this study within a larger
      interventional study. In that study--a pragmatic randomized clinical pilot trial-
      the team developed a model for integrative medicine that combines complementary
      therapies that have an emerging evidence base and conventional treatments for
      patients with nonspecific back and neck pain. The research team implemented the
      model and compared the results for integrative care to results for conventional
      primary care. The current qualitative study included 11 focus-group discussions:
      conventional care (n= 5) and integrative care (n=6). SETTING: The research team
      implemented the interventional study in south suburban Stockholm, an area with
      higher unemployment, lower incomes, and receipt of more welfare support and
      sickness benefits compared to the average levels in Stockholm. PARTICIPANTS: The
      participants in the focus-group discussions were volunteers drawn from the larger
      randomized clinical trial. OUTCOME MEASURES: The research team transcribed all
      discussions from the focus groups verbatim and used latent content analysis to
      evaluate the data. RESULTS: Receiving diagnostic support and excluding pathology
      were strong reasons for participants to seek conventional care. Participants
      reported that they found conventional management to be reductionistic, with a
      focus on disease, and a lack of accessibility, time, and guidance. In contrast,
      participants reported that integrative care was holistic, whole-person management
      and facilitated increased treatment response, support, empowerment, and self-help
      strategies. Participants, however, perceived integrative care to be challenging
      because of additional treatment costs with complementary therapies and
      collaborative shortcomings between integrative and conventional practitioners
      generally. CONCLUSION: Integrative care represents a combination of valuable
      conventional medical diagnosis with empowering self-help strategies for some
      patients with nonspecific back and neck pain in Swedish primary care. Future
      studies should also investigate experiences and perceptions in the longer term
      from the perspective of patients, caregivers, and health systems.

PMID- 22875560
TI  - Yoga and exercise for symptoms of depression and anxiety in people with
      poststroke disability: a randomized, controlled pilot trial.
AB  - CONTEXT: Mood disorders are prevalent in people after stroke, and a disorder's
      onset can exacerbate stroke-related disabilities. While evidence supports the
      mental-health benefits of participation in exercise and yoga, it is unknown
      whether such benefits extend to a population with poststroke hemiparesis.
      OBJECTIVE: The study investigated whether supplementing exercise with
      participation in a yoga program would provide further improvements in self
      reported symptoms of depression and anxiety in a chronic poststroke population,
      and it also assessed trial feasibility for future studies. DESIGN: The research
      team designed a randomized, controlled pilot trial that included an exercise-only
      group (EX, control) and a yoga-and-exercise group (YEX, intervention). SETTING:
      The study took place at the Centre for Physical Activity in Ageing an exercise
      rehabilitation and activity center at the Royal Adelaide Hospital in South
      Australia. PARTICIPANTS: The participants included 14 individuals with chronic
      poststroke hemiparesis: eight in the intervention group and six in the control
      group. INTERVENTIONS: The YEX group participated in a 6-week standardized program
      that included yoga in weekly group sessions and home practice in addition to
      exercise in a weekly group class. The EX group participated only in the group
      exercise class weekly for 6 weeks. OUTCOME MEASURES: The research team assessed
      self-reported symptoms of depression using the Geriatric Depression Scale (GDS15)
      and symptoms of anxiety and negative affect using the State Trait Anxiety
      Inventory (STAI). The team based the feasibility evaluation on recruitment
      outcomes, retention of participants, participants' compliance with the
      intervention program, and the safety of the intervention. RESULTS: Changes in
      depression and state and trait anxiety did not significantly differ between
      intervention groups (GDS15 P=.749, STAI-Y1, P=.595, STAI-Y2, P=.407). Comparison
      of individuals' case results indicated clinically relevant improvements in both
      groups, although members of the intervention group had greater improvements.
      Participants reported no adverse events, and the study experienced high retention
      of participants and high compliance in the yoga program. CONCLUSIONS: This pilot
      study provides preliminary data on the effects of yoga combined with exercise to
      influence mood poststroke. It is a feasible, safe, and acceptable intervention,
      and the field requires additional investigations with a larger sample size.

PMID- 22875561
TI  - Effectiveness of acupuncture in treatment of facial spasm: a meta-analysis.
AB  - CONTEXT: Facial spasm is one of the common facial diseases, especially in the
      aged. It is mostly characterized by initially progressive, involuntary,
      irregular, recurrent, clonic, or tonic movements of muscles innervated by the
      facial nerve on one side. Acupuncture is a low-risk treatment with purported
      claims of effectiveness for facial spasm. OBJECTIVE: To assess the efficacy of
      acupuncture in facial spasm comprehensively. DESIGN: The research team conducted
      a systematic review and meta-analysis of all randomized clinical trials (RCTs)
      that examined the effectiveness of acupuncture for facial spasm. OUTCOME
      MEASURE(S): The research team categorized results from each of the reviewed
      studies in two ways: (1) the number of participants who showed a positive
      response to therapy (total effectiveness rate) and (2) the number of participants
      who made a full recovery (clinical cure rate). RESULTS: The research team
      reviewed a total of 13 studies involving 1262 participants with facial spasm.
      Researchers in China had conducted all studies, and most studies were poor in
      methodological quality. All studies reported that acupuncture was superior to
      other treatments, including carbamazepine, mecobalamin, and massage, and the meta
      analysis on these low-quality studies yielded similar results. CONCLUSION:
      Present trials evaluating the efficacy of acupuncture in treatment of facial
      spasm are mostly poor in methodological quality. These studies showed that
      acupuncture was superior to other treatments for facial spasm; however, in its
      meta-analysis, the research team could not draw an affirmative conclusion as to
      the benefits of acupuncture due to the poor methodological quality and localized
      population of the included trials. The field needs large international, well
      conducted RCTs.

PMID- 22875562
TI  - Stanislaw R. Burzynski, MD, PhD: novel cancer research and the fight to prove its
      worth.

PMID- 22875563
TI  - Making sense of mobile health data: an open architecture to improve individual-
      and population-level health.
AB  - Mobile phones and devices, with their constant presence, data connectivity, and
      multiple intrinsic sensors, can support around-the-clock chronic disease
      prevention and management that is integrated with daily life. These mobile health
      (mHealth) devices can produce tremendous amounts of location-rich, real-time,
      high-frequency data. Unfortunately, these data are often full of bias, noise,
      variability, and gaps. Robust tools and techniques have not yet been developed to
      make mHealth data more meaningful to patients and clinicians. To be most useful,
      health data should be sharable across multiple mHealth applications and connected
      to electronic health records. The lack of data sharing and dearth of tools and
      techniques for making sense of health data are critical bottlenecks limiting the
      impact of mHealth to improve health outcomes. We describe Open mHealth, a
      nonprofit organization that is building an open software architecture to address
      these data sharing and "sense-making" bottlenecks. Our architecture consists of
      open source software modules with well-defined interfaces using a minimal set of
      common metadata. An initial set of modules, called InfoVis, has been developed
      for data analysis and visualization. A second set of modules, our Personal
      Evidence Architecture, will support scientific inferences from mHealth data.
      These Personal Evidence Architecture modules will include standardized, validated
      clinical measures to support novel evaluation methods, such as n-of-1 studies.
      All of Open mHealth's modules are designed to be reusable across multiple
      applications, disease conditions, and user populations to maximize impact and
      flexibility. We are also building an open community of developers and health
      innovators, modeled after the open approach taken in the initial growth of the
      Internet, to foster meaningful cross-disciplinary collaboration around new tools
      and techniques. An open mHealth community and architecture will catalyze
      increased mHealth efficiency, effectiveness, and innovation.

PMID- 22875564
TI  - 2-D gel-based proteomic approaches to antibiotic drug discovery.
AB  - The global analysis of changes in the protein composition of bacterial cells in
      response to treatment with antibiotic agents grants insights into the
      physiological response of cells to inhibition of vital cellular functions. This
      unit gives an overview of how global proteomic studies can impact antibacterial
      drug discovery by identifying or validating compound mechanism of action and by
      increasing the confidence in the value of genes with unknown function as
      potential new targets. It describes the design and function of a reference
      compendium of proteomic responses to inhibition of vital cellular functions
      through antibacterial agents or genetic down-regulation of potential target
      genes. An overview of the workflow for two-dimensional gel electrophoresis-based
      experiments is also presented.

PMID- 22875565
TI  - Production and discovery of novel recombinant adeno-associated viral vectors.
AB  - In this unit, we describe the detailed procedure for a three-plasmid transfection
      method for rAAV production, and discuss its advantages, limitations, and
      troubleshooting techniques. We further discuss the rAAV purification process
      using CsCl gradients, as well as subsequent quality control methods using SDS
      PAGE and real-time PCR to assess vector purity, packaging efficiency, and viral
      titer. Finally, we elaborate on a PCR-based strategy that can be used to discover
      novel AAV capsid sequences from primate tissue, which can be used to develop
      newer-generation rAAVs with a greater diversity of tissue tropism for clinical
      gene therapy.

PMID- 22875566
TI  - Gene transfer in the lung using recombinant adeno-associated virus.
AB  - Adeno-associated virus (AAV) is a small replication-deficient DNA virus belonging
      to the Parvovirinae family. It has a single-stranded ~4.7-kb genome. Recombinant
      AAV (rAAV) is created by replacing the viral rep and cap genes with the transgene
      of interest along with promoter and polyadenylation sequences. The short viral
      inverted terminal repeats must remain intact for replication and packaging in
      production, as well as vector genome processing and persistence in the
      transduction process. The AAV capsid (serotype) determines the tissue tropism of
      the rAAV vector. In this unit we will discuss serotype selection for lung
      targeting along with the factors effecting efficient delivery of rAAV vectors to
      the murine lung. Detailed procedures for lung delivery (intranasal, orotracheal,
      and surgical tracheal injection), sample collection, and post-mortem tissue
      processing will be described.

PMID- 22875567
TI  - Detection, isolation, and identification of Vibrio cholerae from the environment.
AB  - Recent molecular advances in microbiology have greatly improved the detection of
      bacterial pathogens in the environment. These improvements and a downward trend
      in the cost of molecular detection methods have contributed to increased
      frequency of detection of pathogenic microorganisms where traditional culture
      based detection methods have failed. Culture methods also have been greatly
      improved, and the confluence of the two suites of methods provides a powerful
      tool for detection, isolation, and characterization of pathogens. While molecular
      detection provides data on the presence and type of pathogens, culturing methods
      allow a researcher to preserve the organism of interest for "-omics" studies,
      such as genomic, metabolomic, secretomic, and transcriptomic analysis, which are
      rapidly becoming more affordable. This has yielded a clearer understanding of the
      ecology and epidemiology of microorganisms that cause disease. In this unit, we
      present commonly accepted methods for isolation, detection, and characterization
      of V. cholerae, providing more extensive knowledge of the ecology and
      epidemiology of this organism. This unit has been fully revised and updated from
      the earlier version with the latest knowledge and additional information not
      previously included.

PMID- 22875568
TI  - Isolation and classification of Bdellovibrio and like organisms.
AB  - Bdellovibrio and like organisms (BALOs) are obligate predators of Gram-negative
      bacteria. BALOs are isolated as plaques growing at the expense of their prey and
      are cultivated as two-member cultures. The growth cycle is composed of an
      extracellular attack phase and an intraperiplasmic elongation and replication
      phase. However, there are methods for obtaining host-independent (HI) mutants
      that grow without prey on rich media. BALOs are commonly found in the environment
      but generally constitute small populations; therefore, their isolation may
      require enrichment steps. Contamination by other bacteria during isolation
      necessitates efficient separation between the smaller BALO cells from the
      majority of larger bacteria. BALOs can also be directly detected and quantified
      in environmental samples using specific PCR. Synchronous cultures of both wild
      type and HI derivatives can be obtained to study the different growth phases.
      These can be further separated by centrifugation. Classification is based on 16S
      rDNA analysis. Protocols relevant to these aspects of BALO detection, isolation,
      growth, classification, and quantitation are presented in this unit.

PMID- 22875570
TI  - [Quo vadis rheumatology: Closed conference of the executive board and advisory
      committee of the German Society for Rheumatology 2011].

PMID- 22875571
TI  - [Intracellular signaling transduction pathways. Potential targets in the
      treatment of rheumatic diseases].
AB  - Even though biologics, frequently combined with conventional DMARD therapy,
      represent a significant advance in the treatment of rheumatic diseases, they have
      disadvantages such as high costs of production and parenteral administration.
      Therefore, oral small-molecule drugs are a potential alternative. Major targets
      for such small-molecule therapeutics are intracellular signaling molecules. This
      article will briefly discuss potential intracellular targets for therapeutics in
      the field of rheumatic diseases. How therapeutic signaling inhibitors will be
      used in clinical practice will depend on a number of factors: their overall
      effectiveness, their effectiveness in patients who did not or insufficiently
      respond to conventional DMARD therapy and/or treatment with biologics, their
      effectiveness when combined with other therapeutics, their side effects, and
      their cost-benefit ratio.The English full-text version of this article is
      available at SpringerLink (under "Supplemental").

PMID- 22875572
TI  - [Management of nonspecific low back pain. The new national guidelines 2011].
AB  - Low back pain is a frequent health problem and causes substantial costs. Between
      2007 and 2010 a panel of interdisciplinary experts in Germany developed evidence
      based national guidelines for the management of nonspecific low back pain. These
      guidelines cover diagnosis (red flags and yellow flags), treatment
      recommendations and health care algorithms. In acute nonspecific low back pain
      diagnostic imaging is not indicated and should be avoided. Education and patient
      information, maintenance of routine daily physical activities and pain therapy as
      needed are the cornerstones of acute nonspecific low back pain therapy. In order
      to prevent the development of chronic back pain in patients with acute
      nonspecific back pain, the early identification of parameters predictive of a
      high risk of chronicity (yellow flags)   is of particular importance even in
      primary care.

PMID- 22875575
TI  - Role of 18F-FDG PET-CT for evaluating the response to reduced-intensity
      conditioning allogeneic transplant in heavily pre-treated patients with chronic
      lymphocytic leukemia: preliminary results in nine patients.
AB  - OBJECTIVE: The aim of our preliminary study was to evaluate the potential role of
      18F-FDG PET-CT in monitoring response to reduced-intensity conditioning (RIC)
      transplant in a small series of chronic lymphocytic leukemia (CLL) patients and
      to compare the results with those obtained by standard criteria. METHODS: We
      retrospectively analyzed 9 consecutive refractory/relapsed CLL patients, who
      underwent RIC transplant from March 2004 until May 2009. PET-CT was planned at 6
      8 months after transplant to assess response and at a mean of 6 months during
      follow-up. The mean long-term follow-up period was 38 months (range 12-74 months,
      median 29 months). RESULTS: The first PET-CT showed abnormal 18F-FDG uptake in
      five patients, while by standard criteria eight patients showed persistent
      disease. At the end of follow-up (mean 38 months), all four patients with
      previously negative scan were still PET negative and in complete remission by
      standard criteria. All five patients with previously positive scan were still PET
      positive: one patient died for disease progression and four are alive with
      disease. CONCLUSIONS: Our preliminary data, although in a small series of CLL
      patients, suggest that the metabolic findings revealed at first PET-CT after
      transplant seem to predict the patient outcome and to assess the metabolic
      disease status earlier than clinical evaluation by standard criteria. PET-CT
      performed during follow-up may be useful to early detect disease progression.

PMID- 22875576
TI  - Efficacy of 99mTc-sestamibi SPECT/CT for minimally invasive parathyroidectomy:
      comparative study with 99mTc-sestamibi scintigraphy, SPECT, US and CT.
AB  - PURPOSE: We evaluated the efficacy of (99m)Tc-sestamibi SPECT/CT for planning
      minimally invasive parathyroidectomy (MIP), comparing with dual phase (99m)Tc
      sestamibi scintigraphy, (99m)Tc-sestamibi SPECT and conventional imaging (US and
      CT). METHODS: Thirty-one patients (M:F = 10:21, range 35-78 years old) who showed
      high serum parathyroid hormone (intact PTH) level were included. (99m)Tc
      sestamibi scintigraphy was performed 15 and 150 min after injection of (99m)Tc
      sestamibi (555 MBq), and (99m)Tc-sestamibi SPECT/CT was obtained just after the
      delayed scan. Comparison study between imaging modalities was done by patient
      based and lesion location-based analysis. The location of the lesion was
      confirmed by the operative finding. An operation was performed in 24 patients.
      Seven patients had normal (99m)Tc-sestamibi SPECT/CT, and followed for more than
      6 months after SPECT/CT. RESULTS: Among 24 patients, parathyroid adenoma was
      detected in 19 patients and the other 5 had parathyroid hyperplasia (total 35
      lesions). (99m)Tc-sestamibi scintigraphy detected abnormal uptake in 15 patients
      with 24 lesions. Conventional imaging identified abnormal findings in 17 patients
      with 27 lesions. SPECT detected abnormal findings in 18 patients with 27 lesions.
      SPECT/CT identified abnormal findings in 24 patients with 35 lesions. SPECT/CT
      demonstrated 100 % sensitivity in a patient-based analysis. SPECT/CT exhibited
      significantly better sensitivity than (99m)Tc-sestamibi scintigraphy, SPECT and
      conventional imaging (p < 0.05). All lesion location was correctly identified to
      perform MIP. The final clinical diagnosis of 7 normal SPECT/CT patients was
      secondary hyperparathyroidism on 6 months follow-up. CONCLUSIONS: We correctly
      identified the precise location of parathyroid adenomas or hyperplasia by (99m)Tc
      sestamibi SPECT/CT which was helpful to perform MIP.

PMID- 22875577
TI  - Diagnostic performance of planar scintigraphy using 99mTc-MIBI in patients with
      secondary hyperparathyroidism: a meta-analysis.
AB  - OBJECTIVE: Parathyroid scintigraphy using (99m)Tc-MIBI is not currently
      considered a valuable diagnostic tool for the localization of involved glands in
      patients with secondary hyperparathyroidism (SHPT). However, published data about
      its diagnostic accuracy are discordant and a meta-analysis about this topic is
      still lacking. The aim of our study is to meta-analyze the published data about
      the diagnostic performance of (99m)Tc-MIBI parathyroid scintigraphy in patients
      with SHPT. METHODS: A comprehensive computer literature search of studies
      published in PubMed/MEDLINE, Scopus and Embase databases through September 2011
      and regarding the diagnostic accuracy of (99m)Tc-MIBI parathyroid scintigraphy in
      patients with SHPT was carried out. Only articles in English language in which at
      least 10 patients with SHPT underwent planar (99m)Tc-MIBI parathyroid
      scintigraphy were selected. Pooled sensitivity, pooled specificity and area under
      the ROC curve on a per lesion-based analysis were calculated to measure the
      diagnostic accuracy of (99m)Tc-MIBI parathyroid scintigraphy in SHPT patients.
      RESULTS: Twenty-four studies comprising 471 patients were included in this meta
      analysis. The pooled sensitivity and specificity of (99m)Tc-MIBI parathyroid
      scintigraphy in detecting hyperplastic glands in SHPT patients were 58 % [95 %
      confidence interval (95 % CI) 52-65 %] and 93 % (95 % CI 85-100 %), respectively,
      on a per lesion-based analysis. Area under ROC curve was 0.75. CONCLUSIONS: In
      patients with SHPT and diffuse or nodular hyperplasia, planar parathyroid
      scintigraphy using (99m)Tc-MIBI has demonstrated an inadequate diagnostic
      accuracy. Therefore, it should not be considered as a first-line diagnostic
      imaging method in the pre-surgical detection of hyperplastic parathyroid glands.

PMID- 22875578
TI  - Variability of tail length in hybrids of the Japanese macaque (Macaca fuscata)
      and the Taiwanese macaque (Macaca cyclopis).
AB  - In primates, tail length is subject to wide variation, and the tail may even be
      absent. Tail length varies greatly between each species group of the genus
      Macaca, which is explained by climatic factors and/or phylogeographic history.
      Here, tail length variability was studied in hybrids of the Japanese (M. fuscata)
      and Taiwanese (Macaca cyclopis) macaque, with various degrees of hybridization
      being evaluated through autosomal allele typing. Relative tail length (percent of
      crown-rump length) correlated well with the number of caudal vertebrae. Length
      profiles of caudal vertebrae of hybrids and parent species revealed a common
      pattern: the length of several proximal-most vertebrae do not differ greatly;
      then from the third or fourth vertebra, the length rapidly increases and peaks at
      around the fifth to seventh vertebra; then the length plateaus for several
      vertebrae and finally shows a gentle decrease. As the number of caudal vertebrae
      and relative tail length increase, peak vertebral length and lengths of proximal
      vertebrae also increase, except that of the first vertebra, which only shows a
      slight increase. Peak vertebral length and the number of caudal vertebrae
      explained 92 % of the variance in the relative tail length of hybrids. Relative
      tail length correlated considerably well with the degree of hybridization, with
      no significant deviation from the regression line being observed. Thus, neither
      significant heterosis nor hybrid depression occurred.

PMID- 22875579
TI  - The posterior surgical correction of congenital kyphosis and kyphoscoliosis: 23
      cases with minimum 2 years follow-up.
AB  - PURPOSE: The purpose of this study is to review our operative experience of
      congenital kyphosis or kyphoscoliosis undergoing either pedicle subtraction
      osteotomy (PSO) or posterior vertebral column resection (pVCR) according to
      certain criteria we have established. METHODS: From December 2003 to 2009, 23
      consecutive patients of congenital kyphosis or kyphoscoliosis were treated by
      means of PSO or pVCR procedure in a single institution. The average preoperative
      kyphosis angle was 74.3o. The C7 plumb line was 12.6 mm posterior to the
      posterior-superior corner of S1 on average, showing negative imbalance. In the 11
      cases who had accompanied scoliosis, the average preoperative scoliosis angle was
      42.6o. The average Oswestry Deficiency Index (ODI) for back pain was 14.6 before
      surgery. Eleven patients had compromise of neurological functions. RESULTS: After
      PSO or pVCR procedure, the average kyphosis angle decreased to 20.0o, and the
      accompanied scoliosis also decreased to 15.8o. The average follow-up time after
      surgery was 34.3 months. At the last follow-up, the average kyphosis corrective
      rate was 73.7 %, and the average scoliosis corrective rate was 61.7 %. The
      negative imbalance improved, with the C7 plumb line being 1.5 mm posterior to the
      posterior-superior corner of S1 on average. After surgery, the average ODI for
      back pain had 40.6 % improvement, and most patients who had neurological symptoms
      before surgery had varying degrees of relief. The total satisfactory rate to
      corrective surgery was 91.3 %. No permanent neurological damage was observed.
      CONCLUSIONS: If selected appropriately, both PSO and pVCR procedures can achieve
      compatible and satisfactory correction results in the surgical treatment of
      congenital kyphosis or kyphoscoliosis.

PMID- 22875580
TI  - Demographic predictors of HIV serostatus among HIV counseling and testing clients
      in rural Nigeria.
AB  - Nnewi is a rural Nigerian town with a human immunodeficiency virus (HIV)
      counseling and testing center which tests about 120 clients/d. The objective of
      this study is to determine the factors predicting positive HIV status at Nnewi.
      Review of records was done with age, gender, marital status, and occupation as
      variables. Logistic regression analysis was used to identify factors linked to a
      positive HIV test. Overall HIV prevalence was 31.14%. Drivers and married clients
      had a high risk of being HIV+ (odds ratio [OR], 3.59; 95% confidence interval
      [CI], 2.17-5.96 and OR, 2.78; 95% CI, 2.42-3.19). Housewives were 2 times more
      likely to be positive (OR, 2.11; 95% CI, 1.35-3.29). After adjustment, females
      had 22% higher risk (OR, 1.22; 95% CI, 1.03-1.45) with the highest chance found
      in married females (OR, 6.70; 95% CI, 4.45-10.09). The study succeeded in panning
      out an unexpected risk group: married women. Drivers have been known to be a risk
      group. Preventive methods must be tailored to and acceptable by each risk group.

PMID- 22875581
TI  - Factors associated with reduced antituberculous serum drug concentrations in
      patients with HIV-TB coinfection.
AB  - We describe correlates of reduced antituberculous serum drug concentrations
      (SDCs) in HIV-infected patients receiving treatment for active tuberculosis (TB).
      Cross-sectional analysis of individuals diagnosed with HIV and active TB in
      Northern Alberta, Canada, was performed. Of the 30 HIV-TB cases, 27 underwent
      measurement of SDCs. Rates of low SDCs were 9 of 26 (34%) for isoniazid (INH) and
      16 of 25 (64%) for rifamycins. Increased weight and elevated body mass index
      (BMI) correlated with low SDCs for rifampin (P < .05) and increased weight also
      correlated with reduced SDCs for INH (P < .05). This suggests that conventional
      antituberculous dosing may be too low and consideration should be given to
      increase the maximum initial weight-based doses in HIV-infected patients.

PMID- 22875582
TI  - HIV risk assessment and risk reduction strategies in the context of prevailing
      gender norms in rural areas of Cabo Delgado, Mozambique.
AB  - Since minimal information exists on how individuals work within existing social
      norms to reduce HIV risk, this study explored the specific factors influencing
      men and women to reduce their HIV risk in the face of prevailing gender norms in
      rural villages of Cabo Delgado, Mozambique. Qualitative data were gathered from
      160 participants through 29 in-depth interviews to explore gender norms, HIV risk
      determinants, and risk reduction responses. Results were analyzed using
      adaptations of grounded theory and constant comparative analysis. Men and women
      who actively take measures to decrease their risk of HIV infection associate a
      partner's acceptance of condom use and an HIV test as confirmation of emotional
      intimacy in the relationship. Other factors influencing risk reduction efforts
      include various levels of influence from family or peers, prior experience,
      relationship dynamics, and a reflection of broader personal outcomes.

PMID- 22875583
TI  - Cavitary pulmonary metastases of pancreas cancer.

PMID- 22875584
TI  - Percutaneous removal of a fully expanded SMART stent from the pulmonary artery
      using various adjunctive techniques.
AB  - A 36-year-old man with an implanted arteriovenous shunt for hemodialysis was
      referred for shunt malfunction. Venography of the right upper extremity showed
      occlusion of the subclavian vein, and a SMART stent was deployed. The fully
      expanded stent immediately migrated centrally into the left pulmonary artery. As
      initial efforts to pass a snare over the stent failed, we intentionally passed a
      microguidewire through stent interstices, snared the end of the microguidewire to
      create a loop, and pulled the stent/microguidewire/snare combination back into
      the right ventricle where it separated from the loop because of stent mesh
      destruction. As the stent remained in the right ventricle, we advanced a 0.035
      in. guidewire into the stent lumen, passed an angioplasty balloon over the
      guidewire, inflated the balloon in the stent, and performed pull-back into the
      right distal external iliac artery. The stent was then surgically removed via a
      right inguinal incision without eliciting any complications. Although retrieval
      of the stent malpositioned in the pulmonary artery was difficult, we retrieved it
      safely by applying various adjunctive techniques.

PMID- 22875585
TI  - Changes in CT density of solitary capillary hemangioma of the lung upon varying
      patient position.
AB  - Solitary capillary hemangioma of the lung (SCHL) is a rare benign tumor that is
      difficult to differentiate from other nodular lesions, including lung cancer, on
      CT. We report a case of 58-year-old man with an SCHL of the left lower lung. A
      nodular lesion 7 mm in size varied in CT appearance when the position of the
      patient was changed: it was part solid and part ground-glass opacity (mixed GGO)
      in the supine position, but pure GGO (nonsolid) in the prone position. However,
      the possibility of a malignancy could not be completely excluded because the
      density of the lesion had increased slightly over the past five years, so the
      patient underwent surgical resection. The histological diagnosis was SCHL.
      Therefore, changes in the CT density of a nodule upon changing patient position
      may indicate an SCHL.

PMID- 22875586
TI  - The sternalis muscle: radiologic findings on MDCT.
AB  - PURPOSE: The purpose of this study was to characterize and determine the
      prevalence of the sternalis muscle using 64-row multidetector computed tomography
      (MDCT). MATERIALS AND METHODS: We retrospectively reviewed MDCT chest scans that
      were performed in a hospital during the course of a month. The study population
      consisted of 948 consecutive patients (511 males and 467 females). On the MDCT
      scans the sternalis muscle was defined as the longitudinal muscle lying on and
      superficial to the pectoralis major muscle. RESULTS: The prevalence of the
      sternalis muscle was 10.5 %. The muscle was present more frequently in females
      (13.0 %) compared to males (8.4 %) (P = 0.02). In the majority of patients, the
      muscle was located longitudinally in the parasternal position; however, in two
      patients it was positioned across the sternum. One hundred twenty were flat
      types, while the remaining five had oblique shapes. The muscle mean height, width
      and depth were 77.9 +/- 25.1, 19.4 +/- 12.2 and 2.8 +/- 1.3 mm, respectively. The
      muscle was wider in males compared to females (P < 0.001). CONCLUSION: Using
      MDCT, its prevalence was shown to be 10.5 %. This variant muscle can be
      differentiated from other pathological structures using its specific
      characteristic appearance.

PMID- 22875587
TI  - Advances in management of premature ventricular contractions.
AB  - Premature ventricular complexes (PVCs) are a common occurrence in clinical
      practice. The clinical presentation may range from asymptomatic to left
      ventricular (LV) dysfunction with congestive heart failure. The decision to
      suppress PVCs is largely based on the presence of symptoms, interference with
      other therapy (e.g., cardiac resynchronization therapy), or suspicion of PVC
      mediated cardiomyopathy. Catheter ablation has emerged as a safe and effective
      option for the treatment of frequent PVCs. Careful attention to PVC
      characteristics on surface electrocardiogram has proven useful for the initial
      localization of the ectopic focus, which may then serve as a guide to procedural
      planning. The point of interest is often identified with activation mapping, and
      the ablation site can be further defined with pace mapping techniques. Clinical
      experience with PVC ablation has been successful in >=80 % of cases, and the
      literature reports multiple cases of marked improvement in LV function after
      eradicating the culprit ectopic focus in patients with PVC-mediated
      cardiomyopathy.

PMID- 22875588
TI  - Vitamin D deficiency in postmenopausal, healthy women predicts increased
      cardiovascular events: a 16-year follow-up study.
AB  - OBJECTIVE: To investigate the relationship between vitamin D status in healthy
      women and cardiovascular outcome. DESIGN AND METHODS: Between 1990 and 1993, 2016
      healthy, recently postmenopausal women were enrolled in the Danish Osteoporosis
      Prevention Study. Serum levels of 25-hydroxyvitamin D (25(OH)D, nmol/l) were
      measured at baseline. Participants were followed for 16 years. The primary end
      point was a combination of death, heart failure, myocardial infarction (MI) and
      stroke. Vitamin D deficiency was defined as serum 25(OH)D<50 nmol/l. The primary
      end point was adjusted for other risk factors of adverse cardiovascular events
      (age, smoking, blood pressure, hip-waist ratio, education and family history of
      MI). RESULTS: At baseline, mean age was 50 years and BMI 25. Women with vitamin D
      deficiency (n=788) had more cardiovascular risk factors than vitamin D-replete
      women (n=1225). Compared with vitamin D-replete women, women with low 25(OH)D
      levels had significantly higher BMI and triglycerides, lower HDL and hip-waist
      ratio and less education. More were smokers among the vitamin D deficient (47 vs
      38%). A primary end point was experienced by 118 (15%) with vitamin D deficiency
      and by 125 (10%) of the vitamin D replete. Hazard ratio (HR) was 1.49 (95%
      confidence interval: 1.16-1.92; P=0.002) in the vitamin D deficient. Adjusted HR
      was 1.32 (1.02-1.71; P=0.03). In total, 135 women died; of these, 65 (8%) were of
      the vitamin D deficient and 70 (6%) in the vitamin D-replete group; unadjusted HR
      was 1.44 (1.02-2.01; P=0.04) for vitamin D deficiency. CONCLUSION: Healthy women
      with vitamin D deficiency have increased risk of adverse cardiovascular outcome.

PMID- 22875589
TI  - The art of medicine.

PMID- 22875590
TI  - Effect of Traumeel S on pain and discomfort in radiation-induced oral mucositis:
      a preliminary observational study.
AB  - CONTEXT: Painful oral mucositis is an almost inevitable side effect of
      radiotherapy of head and neck tumors that simultaneous chemotherapy intensifies
      and that is notoriously difficult to treat. In a previous study, chemotherapy
      induced stomatitis in children undergoing bone marrow transplantation responded
      well to the homeopathic complex remedy Traumeel S. OBJECTIVE: To evaluate the
      efficacy of Traumeel S in the management of radiation-induced oral mucositis in
      patients with head and neck tumors. DESIGN: The research team designed a
      nonrandomized, prospective, observational study with matched pairs. SETTING: The
      research team performed the study in a tertiary cancer-care center at the
      Institute of Radiotherapy and Special Oncology, Medical School Hanover, Germany.
      PARTICIPANTS: The participants were 20 patients who were receiving radiotherapy
      or radiochemotherapy for head and neck tumors. INTERVENTION: Five times per day
      during the observational period, participants self-administered daily mouth
      rinses with either sage tea (Salvia officinalis, control group) or Traumeel S
      solution (intervention group). OUTCOME MEASURES: Two independent physicians
      determined the grade of oral mucositis at least once per week, and the research
      team derived the degree of oral pain from diaries that participants kept.
      RESULTS: Both groups were comparable in terms of tumor and treatment
      characteristics. The research team could not confirm any appreciable specific
      effect of Traumeel S on the primary endpoints; the limited reduction in pain for
      the intervention group compared to the control group was not significant, and the
      more frequent analgesia in the Traumeel S group most likely explained that
      reduction. Among the secondary endpoints, loss of taste and swallowing difficulty
      responded to Traumeel S to some extent. CONCLUSIONS: Traumeel S may have some
      potential in the treatment of radiation-induced oral mucositis, but its possible
      effects need confirmation by further studies. This article discusses some
      methodological requirements.

PMID- 22875591
TI  - New perspectives on complementary and alternative medicine: an overview and
      alternative therapy.
AB  - Since 1990, tremendous progress in the medical sciences has precipitated
      significant improvements in health care. However, with the aging of populations
      worldwide, more people suffer from noncommunicable disease (NCD), incurable
      diseases, and/or poor health. The World Health Organization estimated that of the
      57 million global deaths in 2008, 36 million were due to NCDs. These pose a
      considerable challenge to clinicians worldwide, particularly in developed
      nations. Complementary and alternative medicine (CAM) provides an array of
      treatment modalities for health promotion. CAM therapy can be divided into two
      major strategies; namely, herb-based CAM therapy and non-herb based CAM therapy.
      In the current commentary, we suggest a new understanding of CAM therapy and
      propose a new classification for CAM therapy as well as alternative therapies.
      With such information, CAM can be better utilized to benefit to populations
      worldwide.

PMID- 22875592
TI  - A large cross-sectional, descriptive study of self-reports after biofield therapy
      in Japan: demography, symptomology, and circumstances of treatment
      administration.
AB  - BACKGROUND: Practitioners apply biofield therapy in diverse situations; however,
      most previously published reports investigated its efficacy in a clinical setting
      with a few expert practitioners administering it. OBJECTIVE: The study intended
      to determine the factors associated with self-reported symptom change after a
      single session of Okada Purifying Therapy (OPT), a form of biofield therapy, in
      various settings and to analyze its optimal therapeutic environments. DESIGN:
      This cross-sectional study used simple questionnaires. The research team trained
      100 instructors of OPT to act as investigators for the study. The team recorded
      the initial lecture to those instructors on video, and the instructors used it to
      train other certified OPT practitioners in 222 locations. All investigators were
      volunteers. SETTINGS: The OPT sessions took place in various environments,
      including at MOA International Corporation's affiliated institutes, with or
      without clinics; at investigators' homes; and at participants' homes.
      PARTICIPANTS: The study involved 44 587 participants in total; all were Japanese,
      aged 16 or older, and suffering from physical pain, palpitation/dizziness, or
      anxiety/depression. INTERVENTION: The intervention involved one session of OPT
      lasting 30 minutes or longer administered by the volunteer practitioners. OUTCOME
      MEASURES: The research team evaluated the severity of symptoms before and after
      the intervention. The team examined (1) the self-reported change in each category
      of symptoms as measured after a session and (2) the adjusted odds ratio of the
      variables related to the outcomes. RESULTS: Of the analyzed participants, 69.7%,
      67.5%, and 71.2% reported an improvement in the severity of physical pain,
      palpitation/dizziness, and anxiety/depression, respectively. Those rates,
      however, varied based on the participant's gender, the duration or location of
      the intervention, and the reason for participation. The improvement rate was
      consistently highest among female participants whose reason for participation
      involved a hope that OPT would relieve their symptoms or promote their health and
      who had received the therapy for more than 30 minutes in settings other than
      their own homes. This finding occurred regardless of the recipient's knowledge of
      the therapy or past experience of the intervention. The participant's gender, the
      duration of the intervention, and its location were also significant factors for
      marked improvements (a decrease in symptoms of 2 or 3 levels) in self-reported
      symptoms. In evaluating safety, the research team found that the exacerbation
      rates of reported symptoms were 2.5%, 1.1%, and 0.7% for physical pain,
      palpitation/dizziness, and anxiety/depression, respectively. None of those who
      expressed exacerbation of symptoms needed emergency medical treatment. No factor
      was associated consistently with the exacerbation. CONCLUSION: After a single
      session of biofield therapy, the participants' responses varied according to
      their gender, the duration and location of the intervention, and the reasons for
      participation.

PMID- 22875593
TI  - Immunomodulatory properties of subcellular fractions of a G+ bacterium, Bacillus
      firmus.
AB  - Mucosal immunization with non-living antigens usually requires the use of an
      adjuvant. The adjuvant activity of Bacillus firmus in the mucosal immunization of
      mice was described by our laboratory previously. In the present study,
      subcellular localization of B. firmus activities was followed. After mechanical
      disintegration, subcellular components of bacterium were fractionated by
      differential centrifugation and salting out. Bacterial cell walls, cytoplasmic
      membrane fraction, soluble cytoplasmic proteins, and ribosomal fractions were
      isolated. Their effect on the mouse immune system was studied. Lymphocyte
      proliferation and immunoglobulin formation in vitro were stimulated by bacterial
      cell wall (BCW), cytoplasmic membrane (CMF), and ribosomal fractions. BCW and CMF
      increased antibody formation after intratracheal immunization of mice with
      influenza A and B viruses, and increased protection against subsequent infection
      with influenza virus. The BCW fraction even induced intersubtypic cross
      protection: Mice immunized with A/California/7/04 (H3N2) + BCW were resistant to
      the infection by the highly pathogenic A/PR/8/34 (H1N1) virus.

PMID- 22875594
TI  - Abaxial growth and steric constraints guide leaf folding and shape in Acer
      pseudoplatanus.
AB  - PREMISE OF THE STUDY: How leaf shape is regulated is a long-standing question in
      botany. For diverse groups of dicotyledon species, lamina folding along the veins
      and geometry of the space available for the primordia can explain the palmate
      leaf morphology. Dubbed the kirigami theory, this hypothesis of fold-dependent
      leaf shape regulation has remained largely theoretical. Using Acer
      pseudoplatanus, we investigated the mechanisms behind the two key processes of
      kirigami leaf development. METHODS: Cytological examination and quantitative
      analyses were used to examine the course of the vein-dependent lamina folding.
      Surgical ablation and tissue culturing were employed to test the effects of
      physical constraints on primordia growth. The final morphology of leaves growing
      without steric constraints were predicted mathematically. KEY RESULTS: The
      cytological examination showed that the lamina's abaxial side along the veins
      grows substantially more than the adaxial side. The abaxial hypergrowth along the
      veins and the lamina extension correlated with the lamina folding. When a
      primordium was released from the physical constraints imposed by the other
      primordia, it rapidly grew into the newly available space, while maintaining the
      curvature inward. The morphology of such a leaf was predicted to lack symmetry in
      the lobe shapes. CONCLUSIONS: The enhanced growth on the abaxial side of the
      lamina along the veins is likely to drive lamina folding. The surgical ablation
      provided clear support for the space-filling nature of leaf growth; thus, steric
      constraints play a role in determination of the shapes of folded leaves and
      probably also of the final leaf morphology.

PMID- 22875595
TI  - Proof of principle: supramarginal resection of cerebral metastases in eloquent
      brain areas.
AB  - BACKGROUND: Cerebral metastases are not sharply delimitatable; therefore,
      microsurgical circumferential stripping of intracerebral metastases is often
      insufficient for preventing local tumor recurrence. Supramarginal resection
      significantly improves local tumor control but was suggested not to be suitable
      for metastases in eloquent brain areas. Therefore, we retrospectively analyzed a
      series of patients with cerebral metastases situated in eloquent areas for newly
      occurring neurologic deficits after supramarginal resection performed as awake
      surgery. METHODS: A retrospective analysis was performed for all patients who
      underwent supramarginal resection for a cerebral metastasis performed as awake
      surgery between June 2011 and April 2012. All metastases were localized in
      eloquent brain areas. Pre- and postsurgical neurologic status was documented as
      well as data regarding the primary cancer and histopathologic data. Postoperative
      MRI within 72 h was scheduled routinely to verify complete resection. RESULTS: A
      total of 19 patients underwent awake surgery for a cerebral metastasis in
      eloquent brain areas. Surgery was well tolerated in all patients. Neurologic
      symptoms improved in five patients after surgery. In three patients, neurologic
      deficits existing before surgery worsened. The postoperative median National
      Institute of Health Stroke Scale (NIHSS) score did not differ from the
      preoperative value. CONCLUSIONS: Awake surgery is a feasible tool for metastases
      in eloquent areas, minimizing postoperative neurologic deficits and morbidity.
      Therefore, eloquently situated metastases may also be eligible for supramarginal
      resection. Further studies are needed in order to analyze the benefit of this
      method in achieving better tumor control.

PMID- 22875596
TI  - Association study of CRP gene and ischemic stroke in a Chinese Han population.
AB  - High-sensitivity C-reactive protein (hsCRP) was reported as a strong, independent
      predictor of future myocardial infarction and stroke. It is of importance to
      illustrate the conformance of CRP genetic variation, increment of plasma hsCRP
      and cerebral events. A case-control study including 548 patients with acute
      ischemic stroke and 993 age-matched controls from community-based population was
      conducted and four tagging SNPs (tagSNPs) were genotyped. Multiple logistic
      regression was applied to evaluate the association of CRP gene and stroke hsCRP
      elevation with adjustment for covariates. The results indicated that rs3093059
      and rs3091244 presented statistical associations with ischemic stroke. Odds
      ratios (ORs) (95 % confidence interval [CI]) of additive model, dominant model
      and minor allele at rs3093059 were 0.697 (0.528-0.921), 0.671 (0.487-0.923) and
      0.811 (0.666-0.988), and ORs (95 % CI) of dominant model at rs3091244 was 0.728
      (0.536-0.988), after adjusting for covariates. But there were no significant
      differences of genotype or allele frequencies of the four SNPs observed between
      hypertension (HT) and normal blood pressure (NBP) groups. Further analyses
      indicated the genetic variations of rs876537 and rs3093059 were positively
      associated with increased square root transformed hsCRP and hsCRP elevation (>=3
      mg/l) in ischemic stroke patients, and rs876537 and rs3091244 were associated
      with hsCRP elevation in controls as well. Our finding suggests that the CRP
      genetic polymorphisms were associated with decreased risk of ischemic stroke and
      elevated plasma hsCRP and further replication study and functional research would
      be warranted.

PMID- 22875597
TI  - Targeting early deaths following pancreaticoduodenectomy to improve survival.
AB  - INTRODUCTION: There is increasing focus on disease-specific outcomes. This study
      was undertaken to analyze early mortality after pancreaticoduodenectomy as part
      of a strategy to improve long-term outcome. METHODS: One thousand thirty-one
      patients who underwent pancreaticoduodenectomy from 1992 to 2010 were studied.
      Median data are reported. RESULTS: Fifty-eight (5.6%) patients died within 90
      days after pancreaticoduodenectomy. All patients had at least one significant
      comorbidity, commonly cardiorespiratory in nature (76%). Sixty percent of
      patients had depressed serum albumin levels, and 43% were jaundiced. The American
      Society of Anesthesiologists class was: 17% class II, 72% class III, and 10%
      class IV. Seventy-four percent had malignant disease. Twenty-two percent of
      patients underwent a major vascular resection at the time of
      pancreaticoduodenectomy. Causes of death were vascular/bleeding related (26%),
      cardiorespiratory causes (17%), multiorgan failure (12%), leak/perforation (10%),
      cancer progression (9%), infection (7%), or indeterminate (19%). CONCLUSIONS:
      Death within 90 days after pancreaticoduodenectomy is uncommon, occurs in
      relatively older deconditioned patients, and is generally not causally related to
      underlying malignancy. Early death is generally associated with vascular or
      bleeding complications. Strategies to minimize early death should focus on
      careful patient selection and prompt recognition and management of herald
      bleeding or vascular thrombosis, as it can often result in perioperative death
      following pancreaticoduodenectomy.

PMID- 22875598
TI  - Solitary cavernous hemangioma of the small intestine as the cause of long
      standing iron deficiency anemia.

PMID- 22875599
TI  - Challenges and current methods for attenuation correction in PET/MR.
AB  - Quantitative PET imaging requires an attenuation map to correct for attenuation.
      In stand-alone PET or PET/CT, the attenuation map is usually derived from a
      transmission scan or CT image, respectively. In PET/MR, these methods will most
      likely not be used. Therefore, attenuation correction has long been regarded as
      one of the major challenges in the development of PET/MR. In the past few years,
      much progress has been made in this field. In this review, the challenges faced
      in attenuation correction for PET/MR are discussed. Different methods have been
      proposed to overcome these challenges. An overview of the MR-based (template
      based and voxel-based), transmission-based and emission-based methods and the
      results that have been obtained is provided. Although several methods show
      promising results, no single method fulfils all of the requirements for the ideal
      attenuation correction method for PET/MR. Therefore, more work is still necessary
      in this field. To allow implementation in routine clinical practice, extensive
      evaluation of the proposed methods is necessary to demonstrate robustness and
      automation.

PMID- 22875600
TI  - Cooperative role of antibodies against heat-labile toxin and the EtpA Adhesin in
      preventing toxin delivery and intestinal colonization by enterotoxigenic
      Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrheal
      disease in developing countries, where it is responsible for hundreds of
      thousands of deaths each year. Vaccine development for ETEC has been hindered by
      the heterogeneity of known molecular targets and the lack of broad-based
      sustained protection afforded by existing vaccine strategies. In an effort to
      explore the potential role of novel antigens in ETEC vaccines, we examined the
      ability of antibodies directed against the ETEC heat-labile toxin (LT) and the
      recently described EtpA adhesin to prevent intestinal colonization in vivo and
      toxin delivery to epithelial cells in vitro. We demonstrate that EtpA is required
      for the optimal delivery of LT and that antibodies against this adhesin play at
      least an additive role in preventing delivery of LT to target intestinal cells
      when combined with antibodies against either the A or B subunits of the toxin.
      Moreover, vaccination with a combination of LT and EtpA significantly impaired
      intestinal colonization. Together, these results suggest that the incorporation
      of recently identified molecules such as EtpA could be used to enhance current
      approaches to ETEC vaccine development.

PMID- 22875601
TI  - Treatment with the interleukin-17A-blocking antibody secukinumab does not
      interfere with the efficacy of influenza and meningococcal vaccinations in
      healthy subjects: results of an open-label, parallel-group, randomized single
      center study.
AB  - Our objective was to evaluate the efficacy of influenza and meningococcal
      vaccinations in healthy subjects exposed to the anti-interleukin-17A (IL-17A)
      monoclonal antibody (MAb) secukinumab. We used an open-label, parallel-group,
      randomized single-center study of 50 healthy subjects. Subjects received a single
      150-mg dose of secukinumab or no treatment, followed by vaccination with
      inactivated trivalent subunit influenza virus and conjugate group C meningococcal
      vaccine (Agrippal and Menjugate, respectively) 2 weeks later. Primary efficacy
      variables were responses of >=4-fold increases in antibody titer
      (hemagglutination inhibition [HI; for influenza virus] and serum bactericidal
      assay [SBA; for Neisseria meningitides]) for meningococcus and influenza (at
      least two out of three serotypes), both at 4 weeks postvaccination. All subjects
      randomized to secukinumab (n = 25) or the control (n = 25) completed the study.
      Antibody responses to vaccinations measured at 4 weeks were comparable in both
      groups, with >=4-fold increased responses following influenza virus vaccination
      of 20/25 (80%) for both groups and following meningococcal vaccination of 19/25
      (76%) for the secukinumab group and 18/25 (72%) for the control group.
      Differences between groups were 0% (90% confidence intervals [CI], 19 and 19%)
      and 4% (90% CI, 16 and 24%) for influenza virus and meningococcal vaccines,
      respectively. Antibody responses were comparable between the 2 groups at
      different time points. Headache was the most frequently reported adverse effect.
      No deaths or serious adverse events were reported. Blockade of IL-17A by
      secukinumab does not appear to interfere with efficacy of influenza and
      meningococcal vaccinations, as assessed by the achievement of protective antibody
      levels. A protective (>=4-fold) immune response to both vaccinations at 4 weeks
      was achieved in 80 and 76% of subjects exposed to secukinumab and the control,
      respectively.

PMID- 22875602
TI  - Relapse of systemic juvenile idiopathic arthritis after influenza vaccination in
      a patient receiving tocilizumab.
AB  - We report the case of a patient with systemic juvenile idiopathic arthritis (s
      JIA) receiving tocilizumab (TCZ) who experienced relapses of s-JIA after
      receiving influenza vaccination. Systemic symptoms of s-JIA might be masked
      during TCZ therapy. Careful observation with the monitoring of serum interleukin
      (IL)-18 and IL-6 levels may be useful.

PMID- 22875603
TI  - Interlaboratory standardization of the sandwich enzyme-linked immunosorbent assay
      designed for MATS, a rapid, reproducible method for estimating the strain
      coverage of investigational vaccines.
AB  - The meningococcal antigen typing system (MATS) sandwich enzyme-linked
      immunosorbent assay (ELISA) was designed to measure the immunologic cross
      reactivity and quantity of antigens in target strains of a pathogen. It was first
      used to measure the factor H-binding protein (fHbp), neisserial adhesin A (NadA),
      and neisserial heparin-binding antigen (NHBA) content of serogroup B
      meningococcal (MenB) isolates relative to a reference strain, or "relative
      potency" (RP). With the PorA genotype, the RPs were then used to assess strain
      coverage by 4CMenB, a multicomponent MenB vaccine. In preliminary studies, MATS
      accurately predicted killing in the serum bactericidal assay using human
      complement, an accepted correlate of protection for meningococcal vaccines. A
      study across seven laboratories assessed the reproducibility of RPs for fHbp,
      NadA, and NHBA and established qualification parameters for new laboratories. RPs
      were determined in replicate for 17 MenB reference strains at laboratories A to
      G. The reproducibility of RPs among laboratories and against consensus values
      across laboratories was evaluated using a mixed-model analysis of variance.
      Interlaboratory agreement was very good; the Pearson correlation coefficients,
      coefficients of accuracy, and concordance correlation coefficients exceeded 99%.
      The summary measures of reproducibility, expressed as between-laboratory
      coefficients of variation, were 7.85% (fHbp), 16.51% (NadA), and 12.60% (NHBA).
      The overall within-laboratory measures of variation adjusted for strain and
      laboratory were 19.8% (fHbp), 28.8% (NHBA), and 38.3% (NadA). The MATS ELISA was
      successfully transferred to six laboratories, and a further laboratory was
      successfully qualified.

PMID- 22875604
TI  - Serum IgM antibodies contribute to high levels of opsonophagocytic activities in
      toddlers immunized with a single dose of the 9-valent pneumococcal conjugate
      vaccine.
AB  - In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG
      antibody concentrations to pneumococcal capsular polysaccharides (PPSs) are
      usually determined, along with the opsonophagocytic activity (OPA) of
      antipneumococcal antibodies. We aimed to determine the role of both IgG and IgM
      in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM
      antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were
      measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1
      month after a single PCV9 dose. The OPA for the same serotypes was measured by
      multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations
      and MOPA were measured to PPS of serotypes 6A, 14, and 19F in sera collected 12
      months after vaccination. The detected MOPA titers were high in comparison to the
      IgG concentrations 1 month after immunization. The IgM concentrations were higher
      than IgG concentrations for serotypes 6A and 14 (P < 0.001) and as high as IgG
      for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations
      with MOPA (r = 0.35 to 0.65) was stronger compared to that of the IgG antibodies
      (r = 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera
      only slightly decreased the OPA activity against serotype 14. At 12 months after
      immunization, 50 to 100% of serum samples still showed detectable MOPA activity
      against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to
      OPA 1 month after a single PCV9 vaccination in toddlers and that functionally
      active IgM and IgG antibodies persist for at least a year.

PMID- 22875606
TI  - Electrospun emodin polyvinylpyrrolidone blended nanofibrous membrane: a novel
      medicated biomaterial for drug delivery and accelerated wound healing.
AB  - In this work, blended nanofibrous membranes were prepared by an electrospinning
      technique with polyvinylpyrrolidone (PVP) K90 as the filament-forming polymer,
      and emodin, an extract of polygonum cuspidate known as a medicinal plant, as the
      treatment drug. Detailed analysis of the blended nanofibrous membrane by scanning
      electron microscopy, Differential scanning calorimetry and X-ray diffraction
      revealed that emodin was well distributed in the ultrafine fibers in the form of
      amorphous nanosolid dispersions. Results from attenuated total reflectance
      Fourier transform infrared spectra suggested that the main interactions between
      PVP and emodin might be mediated through hydrogen bonding. In vitro dissolution
      tests proved that the blended nanofibrous membrane produced more desired release
      kinetics of the entrapped drug (emodin) as compared to the pure drug.
      Furthermore, wound healing test and histological evaluation revealed that the
      emodin loaded nanofibrous membrane to be more effective as a healing accelerator
      thereby proving potential strategies to develop composite drug delivery system as
      well as promising materials for future therapeutic biomedical applications.

PMID- 22875605
TI  - The influence of plasma technology coupled to chemical grafting on the cell
      growth compliance of 3D hydroxyapatite scaffolds.
AB  - The development of advanced materials with biomimetic features in order to elicit
      desired biological responses and to guarantee tissue biocompatibility is recently
      gaining attention for tissue engineering applications. Bioceramics, such as
      hydroxyapatite-based biomaterials are now used in a number of different
      applications throughout the body, covering all areas of the skeleton, due to
      their biological and chemical similarity to the inorganic phases of bones. When
      bioactive sintered hydroxyapatite (HA) is desired, biomolecular modification of
      these materials is needed. In the present work, we investigated the influence of
      plasma surface modification coupled to chemical grafting on the cell growth
      compliance of HA 3D scaffolds.

PMID- 22875607
TI  - Preparation and characterization of mesoporous bioactive glass/polycaprolactone
      nanofibrous matrix for bone tissues engineering.
AB  - A polycaprolactone (PCL) nanofibrous composite matrix having mesoporous bioactive
      glass nanoparticles (MBG) was fabricated using the electrospinning method, and
      the microstructural, physical and biological properties of the composite matrix
      were characterized. The fiber diameters of PCL, 5 % MBG/PCL (5 M-PCL) and 10 %
      MBG/PCL (10 M-PCL) were 575 +/- 162 nm, 312 +/- 134 nm and 321 +/- 144 nm,
      respectively. The bioactivity of the composite matrix was evaluated by soaking
      the matrix in 1.5* simulated body fluid; the MBG/PCL matrix showed a better
      biomineralization capability than did the PCL matrix. The biological performance
      of the PCL and the MBG/PCL were evaluated using an in vitro culture of MG63
      osteoblast-like cells. We found that the cell attachment and proliferation rates
      were significantly higher on the 10 M-PCL than on the PCL. Moreover, the
      expression of several genes, including ANX-V, type I collagen and OCN, ALP
      activity, the deposition of calcium, and the BSP protein, were also significantly
      higher on 10 M-PCL than PCL. These results indicated that MBG/PCL has the ability
      to support cell attachment, growth, and differentiation and can also yield high
      bioactivity. Therefore, MBG/PCL could be potentially applied in bone implants.

PMID- 22875608
TI  - Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from
      protopanaxadiol during ginsenoside biosynthesis in Panax ginseng.
AB  - Ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs,
      and the root of this plant contains pharmacologically active components, called
      ginsenosides. Ginsenosides, a class of tetracyclic triterpene saponins, are
      synthesized from dammarenediol-II after hydroxylation by cytochrome P450 (CYP)
      and then glycosylation by a glycosyltransferase. Protopanaxadiol synthase, which
      is a CYP enzyme (CYP716A47) that catalyzes the hydroxylation of dammarenediol-II
      at the C-12 position to yield protopanaxadiol, was recently characterized. Here,
      we isolated two additional CYP716A subfamily genes (CYP716A52v2 and CYP716A53v2)
      and determined that the gene product of CYP716A53v2 is a protopanaxadiol 6
      hydroxylase that catalyzes the formation of protopanaxatriol from protopanaxadiol
      during ginsenoside biosynthesis in P. ginseng. Both CYP716A47 and CYP716A53v2
      mRNAs accumulated ubiquitously in all organs of ginseng plants. In contrast,
      CYP716A52v2 mRNA accumulated only in the rhizome. Methyl jasmonate (MeJA)
      treatment resulted in the obvious accumulation of CYP716A47 mRNA in adventitious
      roots. However, neither CYP716A52v2 nor CYP716A53v2 mRNA was affected by MeJA
      treatment during the entire culture period. The ectopic expression of CYP716A53v2
      in recombinant WAT21 yeast resulted in protopanaxatriol production after
      protopanaxadiol was added to the culture medium. In vitro enzymatic activity
      assays revealed that CYP716A53v2 catalyzed the oxidation of protopanaxadiol to
      produce protopanaxatriol. The chemical structures of the protopanaxatriol
      products were confirmed using liquid chromatography-atmospheric pressure chemical
      ionization mass spectrometry (LC/APCIMS). Our results indicate that the gene
      product of CYP716A53v2 is a protopanaxadiol 6-hydroxylase that produces
      protopanaxatriol from protopanaxadiol, which is an important step in the
      formation of dammarane-type triterpene aglycones in ginseng saponin biosynthesis.

PMID- 22875609
TI  - Identification of IAA transport inhibitors including compounds affecting cellular
      PIN trafficking by two chemical screening approaches using maize coleoptile
      systems.
AB  - The monocot coleoptile tip region has been generally supposed to be the source of
      IAA to supply IAA to basal parts by the polar IAA transport system, which results
      in gravi- and phototropic curvature of coleoptiles. Based on this IAA transport
      system and gravitropism of maize coleoptiles, we have developed two screening
      methods to identify small molecules from a large chemical library that inhibit
      IAA transport. The methods detect molecules that affect (i) gravitropic curvature
      of coleoptiles; and (ii) the amount of IAA transported from the tip. From 10,000
      chemicals, eight compounds were identified and categorized into two groups. Four
      chemicals in group A decreased IAA transport from the tip, and increased
      endogenous IAA levels in the tip. The structures of two compounds resembled that
      of 1-N-naphthylphthalamic acid (NPA), but those of the other two differed from
      structures of known IAA transport inhibitors. Four chemicals in group B strongly
      inhibited IAA transport from the tip, but IAA levels at the tip were only
      slightly affected. At higher concentrations, group B compounds inhibited
      germination of Arabidopsis, similarly to brefeldin A (BFA). Analysis of the
      cellular distribution of PIN2-green fluorescent protein (GFP) and PIN1-GFP in
      Arabidopsis revealed that one of the four chemicals in group B induced
      internalization of PIN1 and PIN2 proteins into vesicles smaller than BFA bodies,
      suggesting that this compound affects cellular vesicle trafficking systems
      related to PIN trafficking. The eight chemicals identified here will be a useful
      tool for understanding the mechanisms of IAA transport in plants.

PMID- 22875610
TI  - ADME of antibody-maytansinoid conjugates.
AB  - The concept of treating cancer with antibody-drug conjugates (ADCs) has gained
      momentum with the favorable activity and safety of trastuzumab emtansine (T-DM1),
      SAR3419, and lorvotuzumab mertansine (IMGN901). All three ADCs utilize
      maytansinoid cell-killing agents which target tubulin and suppress microtubule
      dynamics. Each ADC utilizes a different optimized chemical linker to attach the
      maytansinoid to the antibody. Characterizing the absorption, distribution,
      metabolism, and excretion (ADME) of these ADCs in preclinical animal models is
      important to understanding their efficacy and safety profiles. The ADME
      properties of these ADCs in rodents were inferred from studies with radio-labeled
      ADCs prepared with nonbinding antibodies since T-DM1, SAR3419, IMGN901 all lack
      cross-reactivity with rodent antigens. For studies exploring tumor localization
      and activation in tumor-bearing mice, tritium-labeled T-DM1, SAR3419, and IMGN901
      were utilized. The chemical nature of the linker was found to have a significant
      impact on the ADME properties of these ADCs-particularly on the plasma
      pharmacokinetics and observed catabolites in tumor and liver tissues. Despite
      these differences, T-DM1, SAR3419, and IMGN901 were all found to facilitate
      efficient deliveries of active maytansinoid catabolites to the tumor tissue in
      mouse xenograft models. In addition, all three ADCs were effectively detoxified
      during hepatobiliary elimination in rodents.

PMID- 22875611
TI  - The N676D and G697R mutations in the kinase domain of FLT3 confer resistance to
      the inhibitor AC220.

PMID- 22875612
TI  - A common ancestor more than 10,000 years old for patients with R854Q-related type
      2N von Willebrand's disease in Italy.
AB  - The impaired capacity of von Willebrand factor to carry factor VIII is identified
      as type 2N von Willebrand's disease. R854Q is the most common type 2N mutation,
      and almost the only one identified in Italy. This aim of this study was to
      ascertain whether R854Q mutations in a cohort of Italian patients with type 2N
      von Willebrand's disease originated from a single event or recurrent events.
      Thirteen unrelated Italian families were investigated, analyzing the von
      Willebrand factor gene haplotype associated with the R854Q mutation. A common
      haplotype emerged in all the families, extending from single nucleotide
      polymorphisms rs2166902 to rs216293 over 48.2 kb and including five intragenic
      markers. This haplotype is infrequent in the healthy Italian population (17%
      versus 100%, P<0.0001) and each genetic marker within the said haplotype is
      similarly rare. These data strongly suggest a founder effect, with a single R854Q
      mutation event being the cause of the type 2N von Willebrand's disease in our
      cohort of patients. Using DMLE+ software and the mathematical model of Bengtsson
      and Thomson, it was estimated that the R854Q mutation occurred from 10,000 to
      40,000 years ago, which is consistent with the short dimension of the haplotype
      shared by our patients. Together with the fact that the R854Q mutation seems to
      be limited to Caucasian populations, these findings suggest that a single
      mutational event took place after human populations moved from Africa towards
      Europe.

PMID- 22875613
TI  - Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11
      myeloproliferative syndrome.
AB  - The 8p11 myeloproliferative syndrome is a rare, aggressive myeloproliferative
      neoplasm characterized by constitutively active FGFR1 fusion proteins that arise
      from specific chromosomal translocations and which drive aberrant proliferation.
      Although FGFR1 inhibitors have shown in vitro activity against FGFR1 fusions,
      none are in use clinically and there is a need to assess additional compounds as
      potential therapy. Here we use cell lines and primary cells to investigate
      ponatinib (AP24534). Ponatinib-treated Ba/F3 cells transformed by ZMYM2-FGFR1 and
      BCR-FGFR1 and the FGFR1OP2-FGFR1 positive KG1A cell line showed reduced
      proliferation and decreased survival when compared to control cells. Inhibition
      induced apoptosis and reduced phosphorylation of the FGFR1 fusion proteins and
      substrates. Ponatinib-treated cells from 8p11 myeloproliferative syndrome
      patients (n=5) showed reduced colony growth compared to controls. In one
      evaluable patient, ponatinib specifically reduced numbers of FGFR1-fusion gene
      positive colonies. Ponatinib, therefore, shows considerable promise for the
      treatment of patients with 8p11 myeloproliferative syndrome.

PMID- 22875614
TI  - Clonal patterns of X-chromosome inactivation in peripheral blood cells of female
      patients with chronic idiopathic neutropenia.

PMID- 22875615
TI  - Parameters detected by geriatric and quality of life assessment in 195 older
      patients with myelodysplastic syndromes and acute myeloid leukemia are highly
      predictive for outcome.
AB  - Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of
      treatment allocation in older patients as options range from best supportive
      care, non-intensive treatment (e.g. hypomethylating agents) to intensive
      chemotherapy/hematopoietic cell transplantation. Novel metrics for non-disease
      variables are urgently needed to help define the best treatment for each older
      patient. We investigated the feasibility and prognostic value of
      geriatric/quality of life assessments aside from established disease-specific
      variables in 195 patients aged 60 years or over with myelodysplastic
      syndromes/acute myeloid leukemia. These patients were grouped according to
      treatment intensity and assessed. Assessment consisted of eight instruments
      evaluating activities of daily living, depression, mental functioning, mobility,
      comorbidities, Karnofsky Index and quality of life. Patients with a median age of
      71 years (range 60-87 years) with myelodysplastic syndromes (n=63) or acute
      myeloid leukemia (n=132) were treated either with best supportive care (n=47),
      hypomethylating agents (n=73) or intensive chemotherapy/hematopoietic cell
      transplantation (n=75). After selection of variables, pathological activities of
      daily living and quality of life/fatigue remained highly predictive for overall
      survival in the entire patient group beyond disease-related risk factors adverse
      cytogenetics and blast count of 20% or over. In 107 patients treated non
      intensively activities of daily living of less than 100 (hazard ratio, HR 2.94),
      Karnofsky Index below 80 (HR 2.34) and quality of life/'fatigue' of 50 or over
      (HR 1.77) were significant prognosticators. Summation of adverse features
      revealed a high risk of death (HR 9.36). In-depth evaluation of older patients
      prior to individual treatment allocation is feasible and provides additional
      information to standard assessment. Patients aged 60 years or over with newly
      diagnosed myelodysplastic syndromes/acute myeloid leukemia and impairments in
      activities of daily living, Karnofsky Index below 80%, quality of life/'fatigue'
      of 50 or over, are likely to have poor outcomes.

PMID- 22875616
TI  - Transfusion independence and survival in patients with acute myeloid leukemia
      treated with 5-azacytidine.

PMID- 22875617
TI  - Has the time for first-line treatment with second generation tyrosine kinase
      inhibitors in patients with chronic myelogenous leukemia already come? Systematic
      review and meta-analysis.
AB  - Second generation tyrosine kinase inhibitors have recently been introduced as
      first-line treatment for chronic phase chronic myelogenous leukemia. We aimed to
      evaluate the efficacy and safety of 2(nd) generation tyrosine kinase inhibitors
      versus imatinib as first-line treatment for these patients. We carried out a
      systematic review and meta-analysis of randomized controlled trials comparing
      2(nd) generation tyrosine kinase inhibitors to imatinib as first-line treatment
      in chronic phase chronic myelogenous leukemia patients. Outcomes assessed were:
      complete cytogenetic response and major molecular response at 12, 18 and 24
      months, all-cause mortality and progression to accelerated phase/blastic crisis
      at 12, 18 and 24 months, and chronic myelogenous leukemia related mortality and
      toxicity at last follow up. Relative risks were estimated and pooled using a
      fixed effect model. Our search yielded four trials including 2,120 patients. At
      12 months, treatment with 2(nd) generation tyrosine kinase inhibitors
      significantly improved both complete cytogenetic response and major molecular
      response (relative risk 1.16, 95% CI: 1.09-1.23, and 1.68, 95% CI: 1.48-1.91,
      respectively). While major molecular response was improved at all time points,
      complete cytogenetic response improved at 18 months but not at 24 months.
      Importantly, rate of progression to accelerated phase/blastic crisis was
      significantly lower with the newer tyrosine kinase inhibitors throughout all time
      points. Second generation tyrosine kinase inhibitors improved chronic myelogenous
      leukemia related mortality without a statistically significant difference in all
      cause mortality at 12, 18 and 24 months. We conclude that 2(nd) generation
      tyrosine kinase inhibitors can be added safely to the first-line treatment
      armamentarium of chronic phase chronic myelogenous leukemia patients. Although an
      advantage is suggested by surrogate parameters, longer follow up is necessary to
      see if this translates into superior overall survival.

PMID- 22875618
TI  - beta Thalassemia major due to acquired uniparental disomy in a previously healthy
      adolescent.

PMID- 22875619
TI  - MHC class II/ESO tetramer-based generation of in vitro primed anti-tumor T-helper
      lines for adoptive cell therapy of cancer.
AB  - Generation of tumor-antigen specific CD4(+) T-helper (T(H)) lines through in
      vitro priming is of interest for adoptive cell therapy of cancer, but the
      development of this approach has been limited by the lack of appropriate tools to
      identify and isolate low frequency tumor antigen-specific CD4(+) T cells. Here,
      we have used recently developed MHC class II/peptide tetramers incorporating an
      immunodominant peptide from NY-ESO-1 (ESO), a tumor antigen frequently expressed
      in different human solid and hematologic cancers, to implement an in vitro
      priming platform allowing the generation of ESO-specific T(H) lines. We isolated
      phenotypically defined CD4(+) T-cell subpopulations from circulating lymphocytes
      of DR52b(+) healthy donors by flow cytometry cell sorting and stimulated them in
      vitro with peptide ESO(119-143), autologous APC and IL-2. We assessed the
      frequency of ESO-specific cells in the cultures by staining with DR52b/ESO(119
      143) tetramers (ESO-tetramers) and TCR repertoire of ESO-tetramer(+) cells by co
      staining with TCR variable beta chain (BV) specific antibodies. We isolated ESO
      tetramer(+) cells by flow cytometry cell sorting and expanded them with PHA, APC
      and IL-2 to generate ESO-specific T(H) lines. We characterized the lines for
      antigen recognition, by stimulation with ESO peptide or recombinant protein,
      cytokine production, by intracellular staining using specific antibodies, and
      alloreactivity, by stimulation with allo-APC. Using this approach, we could
      consistently generate ESO-tetramer(+) T(H) lines from conventional CD4(+)CD25(-)
      naive and central memory populations, but not from effector memory populations or
      CD4(+)CD25(+) Treg. In vitro primed T(H) lines recognized ESO with affinities
      comparable to ESO-tetramer(+) cells from patients immunized with an ESO vaccine
      and used a similar TCR repertoire. In this study, using MHC class II/ESO
      tetramers, we have implemented an in vitro priming platform allowing the
      generation of ESO-monospecific polyclonal T(H) lines from non-immune individuals.
      This is an approach that is of potential interest for adoptive cell therapy of
      patients bearing ESO-expressing cancers.

PMID- 22875620
TI  - Mutations inDNMT3A and loss of RKIP are independent events in acute monocytic
      leukemia.

PMID- 22875621
TI  - Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta
      analysis of data from individual patients in six randomized trials.
AB  - Treatment with melphalan-prednisone-thalidomide improves the outcome of patients
      with multiple myeloma and is now considered a standard of care for patients not
      eligible for transplantation. However, this treatment is a major source of
      morbidity. A meta-analysis of data from individual patients (n=1680) in six
      randomized trials was performed, comparing the effects of melphalan-prednisone
      thalidomide versus melphalan-prednisone. The main objective was to estimate the
      risk of serious adverse events and their impact on outcome. The primary endpoints
      were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic
      toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6
      months of treatment in both treatment groups. The cumulative incidence of grade 3
      4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group
      than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05
      1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus
      17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were
      significantly increased in patients with poor Performance Status. Occurrence of
      grade 3-4 non-hematologic toxicities had a negative impact on both progression
      free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI
      1.03-1.47). Besides toxicities, progression-free and overall survival were also
      negatively affected by advanced International Staging System stage, high
      creatinine levels and poor Performance Status. Age had a negative impact on
      survival as well. Although melphalan-prednisone-thalidomide improved outcome, it
      increased toxicities, especially non-hematologic ones. Serious non-hematologic
      toxicities, older age, poor Performance Status, and high creatinine levels
      negatively affected survival.

PMID- 22875622
TI  - Association between imatinib transporters and metabolizing enzymes genotype and
      response in newly diagnosed chronic myeloid leukemia patients receiving imatinib
      therapy.
AB  - Imatinib has so far been the first-choice treatment in chronic myeloid leukemia
      with excellent results. However, only a proportion of patients achieve major
      molecular response - hence the need to find biological predictors of outcome to
      select the optimal therapeutic strategy now that more potent inhibitors are
      available. We investigated a panel of 20 polymorphisms in seven genes,
      potentially associated with the pharmacogenetics of imatinib, in a subset of 189
      patients with newly diagnosed chronic myeloid leukemia enrolled in the TOPS
      trial. The analysis included polymorphisms in the transporters hOCT1, MDR1,
      ABCG2, OCTN1, and OATP1A2, and in the metabolizing genes CYP3A4 and CYP3A5. In
      the overall population, the OCTN1 C allele (rs1050152), a simple combination of
      polymorphisms in the hOCT1 gene and another combination in the genes involved in
      imatinib uptake were significantly associated with major molecular response. The
      combination of polymorphisms in imatinib uptake was also significantly associated
      with complete molecular response. Analyses restricted to Caucasians highlighted
      the significant association of MDR1 CC (rs60023214) genotype with complete
      molecular response. We demonstrate the usefulness of a pharmacogenetic approach
      for stratifying patients with chronic myeloid leukemia according to their
      likelihood of achieving a major or complete molecular response to imatinib. This
      represents an attractive opportunity for therapy optimization, worth testing in
      clinical trials.

PMID- 22875623
TI  - TCL1A and ATM are co-expressed in chronic lymphocytic leukemia cells without
      deletion of 11q.
AB  - Chronic lymphocytic leukemia is characterized by the accumulation of B cells that
      are resistant to apoptosis. This resistance is induced by pro-survival stimuli
      from the microenvironment. TCL1 and ATM are central to the pathogenesis of the
      disease and associated with more aggressive disease. Their protein products have
      recently been shown to physically interact in leukemic cells and to impact on NF
      kappaB signaling, which is a key regulator of apoptosis. In the present study we
      show that TCL1 and ATM are significantly co-expressed and up-regulated in
      malignant cells compared to non-malignant B cells, and that expression of TCL1 is
      partially deregulated by aberrant DNA-methylation. In addition, complex external
      stimuli induce essentially similar TCL1 and ATM time-course kinetics. In line
      with a coordinative regulation of NF-kappaB signaling by TCL1, its knockdown
      induced apoptosis in primary leukemia cells. These findings suggest that both
      genes functionally cooperate to modulate similar apoptosis-related cellular
      pathways.

PMID- 22875624
TI  - ETV6 deletion is a common additional abnormality in patients with myelodysplastic
      syndromes or acute myeloid leukemia and monosomy 7.

PMID- 22875625
TI  - Pre-morbid human T-lymphotropic virus type I proviral load, rather than
      percentage of abnormal lymphocytes, is associated with an increased risk of
      aggressive adult T-cell leukemia/lymphoma.
AB  - Out of 153 newly referred human T-lymphotropic virus type I infected patients, 42
      (27%) had 5% or more abnormal lymphocytes, consistent with the diagnosis of
      smoldering adult T-cell leukemia/lymphoma. The abnormal lymphocyte percentage was
      higher in patients with human T-lymphotropic virus type I associated inflammatory
      disease compared with asymptomatic carriers (P=0.006). Over 4.5 years median
      follow up, 4 patients, all with 10 or more human T-lymphotropic virus type I DNA
      copies/100 peripheral blood mononuclear cells at presentation, but only one with
      5% or more abnormal lymphocytes at presentation, developed adult T-cell
      leukemia/lymphoma. Thus, high pre-morbid human T-lymphotropic virus type I
      proviral load, rather than fulfilment of the classification criteria for
      smoldering adult T-cell leukemia/lymphoma, was associated with an increased risk
      of developing aggressive adult T-cell leukemia/lymphoma.

PMID- 22875627
TI  - IKZF1 deletion is an independent predictor of outcome in pediatric acute
      lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.
AB  - IKZF1 gene deletions have been associated with a poor outcome in pediatric
      precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance
      of IKZF1 deletions for patients treated on Berlin-Frankfurt-Munster Study Group
      trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia
      samples by Multiplex Ligation-dependent Probe Amplification. Patients whose
      leukemic cells bore IKZF1 deletions had a lower 5-year event-free survival
      (0.69+/-0.05 vs. 0.85+/-0.01; P<0.0001) compared to those without, mainly due to
      a higher cumulative incidence of relapses (0.21+/-0.04 vs. 0.10+/-0.01; P=0.001).
      Although IKZF1 deletions were significantly associated with the P2RY8-CRLF2
      rearrangement, their prognostic value was found to be independent from this
      association. Thus, IKZF1 deletion is an independent predictor of treatment
      outcome and a strong candidate marker for integration in future treatment
      stratification strategies on ALL-BFM protocols. Clinicaltrials.gov identifier:
      NCT00430118.

PMID- 22875626
TI  - Toward optimizing the use of deferasirox: potential benefits of combined use with
      deferoxamine.
AB  - Patients with beta-thalassemia require iron chelation therapy to protect against
      progressive iron overload and non-transferrin-bound iron. Some patients fail to
      respond adequately to deferoxamine and deferasirox monotherapy while others have
      side effects which limit their use of these drugs. Since combining deferiprone
      and deferoxamine has an additive effect, placing all patients into net negative
      iron balance, we investigated the possibility that combining deferasirox and
      deferoxamine would lead to similar results. We conducted 34-day metabolic iron
      balance studies in six patients in whom the relative effectiveness of deferasirox
      (30 mg/kg/day) and deferoxamine (40 mg/kg/day) was compared, alone and in
      combination. Patients consumed fixed low-iron diets; daily urinary and stool iron
      excretion were determined by atomic absorption. Red blood cell transfusions were
      given prior to each drug treatment to minimize the effects of ineffective
      erythropoiesis. Serial safety measures, hematologic parameters, serum
      chemistries, ferritin levels and urinalyses were determined. All patients were in
      negative iron balance when treated with deferoxamine alone while four of six
      patients remained in positive balance when deferasirox monotherapy was evaluated.
      Daily use of both drugs had a synergistic effect in two patients and an additive
      effect in three others. Five of six patients would be in negative iron balance if
      they used the combination of drugs just 3 days a week. No significant or drug
      related changes were observed in the blood work-ups or urinalyses performed. We
      conclude that supplementing the daily use of deferasirox with 2 - 3 days of
      deferoxamine therapy would place all patients into net negative iron balance
      thereby providing a convenient way to tailor chelation therapy to the individual
      needs of each patient.

PMID- 22875628
TI  - Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements.
AB  - JAK2 fusion genes are rare but recurrent abnormalities associated with diverse,
      clinically heterogeneous hematologic malignancies. Here we assess the JAK1/2
      inhibitor ruxolitinib as therapy for patients with JAK2-rearrangement associated
      myeloproliferative neoplasms (MPN). Ruxolitinib-treated Ba/F3 cells transformed
      to IL3 independence by ETV6-JAK2 showed reduced proliferation and survival
      (IC(50) = 370 nM) compared with KG1A or Ba/F3 cells transformed by BCR-ABL1,
      SPBN1-FLT3 and ZMYM2-FGFR1 (IC(50) > 10 MUM for all). Inhibition was associated
      with reduced phosphorylation of ETV6-JAK2, ERK, STAT5 and AKT. Primary cell
      growth from 2 patients with JAK2 rearrangement and one patient with JAK2
      amplification was assessed in methylcellulose assays. Reduced colony growth was
      seen for all patients in ruxolitinib-treated cultures compared with healthy
      controls (n=7). Fluorescence in situ hybridization showed reduced growth of JAK2
      rearrangement positive colonies compared to JAK2-rearrangement negative colonies.
      Our data, therefore, provide evidence that ruxolitinib is a promising therapy for
      treatment of patients with JAK2 fusion genes.

PMID- 22875629
TI  - A novel validated enzyme-linked immunosorbent assay to quantify soluble
      hemojuvelin in mouse serum.
AB  - Hemojuvelin is a critical regulator of hepcidin expression and can be cleaved by
      proteases to form soluble hemojuvelin. Soluble hemojuvelin has been recently
      identified in human serum but the presence and quantity of soluble hemojuvelin in
      mouse serum is unknown. We developed a two-site enzyme-linked immunosorbent assay
      using a monoclonal anti-hemojuvelin as the capture antibody and a biotinylated
      polyclonal anti-hemojuvelin as the detection antibody to quantify the levels of
      soluble hemojuvelin in mouse serum. We validated this assay using cell
      conditioned media and serum from Hemojuvelin-null and Bone morphogenetic protein
      6-null mice. We also used this validated assay to measure serum soluble
      hemojuvelin concentrations in mice receiving an acute low iron or high iron
      treatment. This two-site enzyme-linked immunosorbent assay was highly specific
      for mouse hemojuvelin, with a lower limit of detection at 13.2-26.8 ng/mL of
      soluble hemojuvelin in mouse serum. The median serum soluble hemojuvelin
      concentration in wild-type C57BL/6J mice was 57.9 +/- 22 ng/mL, which is 4- to 20
      fold less than that reported in healthy human volunteers. After acute low iron
      diet treatment in these mice, serum soluble hemojuvelin levels were increased and
      correlated with lowered serum iron levels and decreased hepatic hepcidin
      expression. An acute high iron diet in wild-type mice or chronically iron
      overloaded Bone morphogenetic protein 6-null mice did not significantly lower
      serum soluble hemojuvelin concentrations. Here we report reliable quantitation of
      mouse serum soluble hemojuvelin using a novel and validated enzyme-linked
      immunosorbent assay. This assay may provide a useful tool to elucidate the source
      and physiological role of serum soluble hemojuvelin in hepcidin regulation and
      iron metabolism using well-established mouse models of iron-related disorders.

PMID- 22875630
TI  - Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195
      conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced
      myeloid malignancies.
AB  - We conducted a phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal
      antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with
      relapsed, refractory myeloid leukemias. Twenty-eight patients received the
      construct intravenously at four dose levels (12, 18, 28 and 40 mg/m(2) per
      course) in a "3+3" study design. The dose-limiting toxicity was infusion-related
      allergic reaction including hypoxia and hypotension. The 28 mg/m(2) total dose
      was considered the maximally tolerated dose. Four patients developed a reduction
      in peripheral blood blasts of at least 50%. Three patients treated with the 10,
      12 and 28 mg/m(2) doses showed a 38-50% reduction in bone marrow blasts. There
      was normalization of platelets in one patient treated with 40 mg/m(2).
      Pharmacokinetic analysis demonstrated that the highest blood levels achieved were
      200-300 ng/mL which cleared with a half-life of ~20 hours. Antigenicity was low
      with one patient at the 12 mg/m(2) dose and one patient at the 18 mg/m(2) dose
      (2/23, <10%) developing antibodies to the recombinant gelonin component after 28
      days. We concluded that HUM-195/rGel can be safely administered in a multi-dose
      cycle to patients with advanced myeloid malignancies and warrants further
      investigation.

PMID- 22875631
TI  - The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1
      independent, autophagy through p38 MAPK pathway.
AB  - Zinc protoporphyrin IX (ZnPPIX), a heme oxygenase-1 enzyme inhibitor, has been
      reported to induce apoptosis and to have antitumor properties. Here, we report
      that ZnPPIX triggers autophagy and causes defective autophagy flux in HeLa cells.
      Autophagosome formation was independent of Beclin 1, indicating non-canonical
      autophagy activity in ZnPPIX-treated cells. Furthermore, western blot results
      indicated that p38 MAPK (mitogen-activated protein kinase) was phosphorylated in
      treated cells. Consistently, SB203580 (a p38 inhibitor) obviously inhibited the
      accumulation of autophagosomes. Our results indicated that p38 MAPK may be a key
      regulator for non-canonical Beclin1-independent autophagy.

PMID- 22875633
TI  - [HIFU in salvage treatment of patients with prostate cancer after primary
      external radiation therapy--status 2012].
AB  - BACKGROUND: Patients with (local) recurrence of prostate cancer after radiation
      therapy face the question of the appropriate diagnostic and possible therapeutic
      options. Many patients in this setting receive palliative androgen deprivation
      therapy alone, with arguable impact on overall cancer survival. In the case of an
      isolated local recurrence, salvage prostatectomy represents a potentially
      curative therapeutic option, albeit with a high complication rate. Alternatively,
      these patients can be offered a local treatment with salvage HIFU therapy.
      MATERIAL AND METHODS: Salvage HIFU therapy is based on the thermal ablation of
      tissue through high-intensity focused ultrasound. In addition, the formation of
      microbubbles (cavitation) and their implosion lead to an enhancement of tissue
      ablation. RESULTS: The results of 6 monocentric studies (2004-2011) with an
      overall number of 408 patients (22-167 patients) are presented and critically
      reviewed. The median follow-up was 18.71 months (7.4-39). The 3-year progression
      free survival (PFS) varied from 25% (D'Amico high risk) to 53% (D'Amico low
      risk), the 5-year overall survival was 90%. The rate of urinary incontinence
      varied between 7 and 60% in all grades (grade III urinary incontinence 0-9.5%).
      In 22 cases surgical incontinence treatment was performed. 53 patients developed
      a urethral stricture or stenosis leading to surgical treatment. Urethral-rectal
      fistulae were seen in 0-7%. CONCLUSIONS: The current data on salvage HIFU can be
      evaluated as insufficient. The main criticisms can be seen in the lack of
      randomization, the monocentric and retrospective analyses of the data, the
      heterogeneous stratification of risk groups as well as inadequate definition of
      postinterventional treatment failure. The studies indicate that salvage HIFU
      therapy leads to a mid-term overall survival with complication rates that are
      comparable to those of other local salvage therapies. Randomized multicentric
      studies are needed to further validate the results of salvage HIFU therapy.

PMID- 22875632
TI  - [Osteoporosis in men receiving androgen deprivation therapy for non-metastatic
      prostate cancer].
AB  - Osteoporosis is defined as a continuous loss of bone mineral density accompanied
      by an increased fracture risk in females and males. A fall of estrogen
      concentrations at the menopause and the consecutive rapid bone loss are an
      established pathogenic mechanism in female osteoporosis. Males do not have a
      menopause equivalent during which significant amounts of bone are lost. Several
      diseases, therapeutic strategies and nutritional deficiencies may also result in
      bone loss and reduced bone mineral density. Prostate cancer is the most common
      visceral malignancy in men. Suppression of endogenous androgen production as a
      therapeutic tool is commonly used in patients with non-metastatic prostate cancer
      and is associated with significant bone loss and an increased fracture risk.
      Androgen deprivation therapy is prescribed both for men with locally advanced or
      high-risk non-metastatic prostate cancer. Osteoclast inhibition with any of
      several bisphosphonates improves bone mineral density and reduces fracture risk.
      Denosumab (a monoclonal antibody against RANK ligand) and toremifene (a selective
      estrogen receptor modulator) recently have been shown to be effective to reduce
      vertebral fractures in patients with non-metastatic prostate cancer receiving
      androgen-deprivation therapy. This overview focuses on cancer-treatment-induced
      bone loss in patients with non-metastatic prostate cancer.

PMID- 22875634
TI  - Live three-dimensional transthoracic echocardiography of giant aorto-right
      ventricular tunnel.

PMID- 22875635
TI  - Long-term decrease in immediate early gene expression after electroconvulsive
      seizures.
AB  - Electroconvulsive therapy (ECT) is a well-established psychiatric treatment for
      severe depression. Despite its clinical utility, post-ECT memory deficits are a
      common side effect. Neuronal plasticity and memory consolidation are intimately
      related to the expression of immediate early genes (IEG), such as Egr1, Fos and
      Arc. Changes in IEG activation have been postulated to underlie long-term
      neuronal adaptations following electroconvulsive seizures (ECS), an animal model
      of ECT. To test this hypothesis, we used real-time PCR to examine the effect of
      acute and chronic ECS (8 sessions, one every other day) on the long-term (>24 h)
      expression of IEG Egr1, Fos and Arc in the hippocampus, a brain region implicated
      both in the pathophysiology of depression as well as in memory function. We
      observed a transient increase in Egr1 and Fos expression immediately after ECS,
      followed by a long-term decrease of IEG levels after both acute and chronic ECS.
      A separate group of animals, submitted to the same chronic ECS protocol and then
      subjected to open field or passive avoidance tasks, confirmed robust memory
      deficits 2 weeks after the last chronic ECS. The possible role of IEG
      downregulation on long-term learning deficits observed following ECS are
      discussed.

PMID- 22875636
TI  - Does structural neuroimaging reveal a disturbance of iron metabolism in
      Parkinson's disease? Implications from MRI and TCS studies.
AB  - A central role of iron in the pathogenesis of Parkinson's disease (PD) has been
      discussed for many years. Numerous studies using magnetic resonance imaging and
      transcranial sonography have been performed to detect alterations in tissue iron
      content of the substantia nigra. This manuscript reviews the findings of this
      still controversial issue and indicates that specific abnormalities that are
      suggested to be related to a disturbance of iron homeostasis may play an early
      role in the pathogenesis of PD.

PMID- 22875639
TI  - Development and validation of a spectrofluorimetric method for the determination
      of erlotinib in spiked human plasma.
AB  - A rapid and sensitive spectrofluorimetric method was developed and validated for
      the determination of erlotinib (ETB), a potent anticancer drug, in spiked human
      plasma without any derivatization. The described method was validated and the
      analytical parameters of linearity, accuracy, precision (intra- and inter-day),
      limit of detection (LOD), and limit of quantification (LOQ) were evaluated. The
      relation between the fluorescence intensity and concentration was found to be
      linear (r(2) 0.9998) over the range 125 to 1000 ng/mL with the detection limit of
      15 ng/mL. A simple liquid-liquid extraction method was followed in order to
      extract the drug from spiked plasma. The mean absolute recoveries of ETB were
      85.59 % (+/-0.57), 86.91 % (+/-1.77) and 89.31 % (+/-3.01) at spiked plasma ETB
      concentration of 5000, 3750 and 2500 ng/mL, respectively. The spectrofluorimetric
      method presented here is a rapid, simple, specific, and reproducible method and
      can be used to characterize the plasma pharmacokinetics of ETB.

PMID- 22875640
TI  - Clinicopathological study of non-palpable familial breast cancer detected by
      screening mammography and diagnosed as DCIS.
AB  - BACKGROUND: Recent widespread use of screening mammography has led to increased
      detection rates of non-palpable breast cancer. This study aimed to evaluate the
      clinicopathological features of non-palpable ductal carcinomas in situ of the
      breast that were detected by screening mammography of patients with a family
      history of breast cancer. METHODS: We selected 6 Japanese patients diagnosed with
      non-palpable breast cancer with self-reported family history of breast cancer.
      Mutations in BRCA1 and BRCA2 were evaluated with germ line genetic testing and
      immunohistochemistry (IHC) using resected specimens. Pathological features, such
      as estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2, were also evaluated. RESULTS: The patients (ages 41-67 years; mean
      53.5) had 7 tumors with one patient having synchronous bilateral breast cancer.
      Breast cancer was suspected from the microcalcification in 5 tumors and the
      distortion in 2 tumors by mammography and diagnosed by biopsy. Breast-conserving
      surgery was performed in 2 patients and mastectomy was performed in 4 patients.
      Genetic testing revealed BRCA2 gene germ line mutation in three patients. IHC of
      BRCA was consistent with BRCA2 mutation status. CONCLUSIONS: The family history
      of breast cancer patients may lead one to suspect familial breast cancer and
      screening mammography is useful for the early detection of these cancers. IHC of
      BRCA showed staining results that were consistent with BRCA genetic testing,
      suggesting that it has the potential to be a useful tool in clinical practice.

PMID- 22875641
TI  - One-step nucleic acid amplification assay (OSNA) for sentinel lymph node biopsy.
AB  - The one-step nucleic acid amplification assay (OSNA) has been developed for the
      intraoperative rapid detection of sentinel lymph node metastasis. Pooled analysis
      of recent studies comparing OSNA with pathology indicated that OSNA is as
      accurate as pathology (96.3 % concordance rate) and is useful for making the
      decision to omit axillary dissection for OSNA-negative patients (97.4 % negative
      predictive value). The advantage of OSNA over pathology is that the former allows
      the semiquantitative evaluation of total tumor volume in the node when a whole
      node is examined. OSNA is expected to be a powerful tool for the estimation of
      risk of non-sentinel lymph node metastasis and also patient prognosis, though
      further studies about this issue with larger numbers of patients is needed. 

PMID- 22875638
TI  - AML1-ETO driven acute leukemia: insights into pathogenesis and potential
      therapeutic approaches.
AB  - The AML1-ETO fusion transcription factor is generated by the t(8;21)
      translocation, which is present in approximately 4%-12% of adult and 12%-30% of
      pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of
      AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the
      absence of secondary events. In this review, we discuss the pathogenetic insights
      that have been gained from identifying the various events that can cooperate with
      AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies
      for t(8;21) positive AML that involve targeting the fusion protein itself, the
      proteins that bind to it, or the genes that it regulates. Recently published
      studies suggest that a targeted therapy for t(8;21) positive AML is feasible and
      may be coming sometime soon.

PMID- 22875642
TI  - A novel taspine derivative, HMQ1611, suppresses adhesion, migration and invasion
      of ZR-75-30 human breast cancer cells.
AB  - BACKGROUND: Taspine was screened for the first time from Radix et Rhizoma
      leonticis (Hong Mao Qi in Chinese) using cell membrane chromatography in our
      laboratory. Its anticancer and antiangiogenic properties were demonstrated, and
      it could serve as a lead compound in anticancer agent development. Here, we
      investigated the role of one of the derivatives, HMQ1611, with increased activity
      and solubility, on the regulation of breast cancer cell ZR-75-30 adhesion,
      migration and invasion. METHODS: The effect of HMQ1611 on adhesion, invasion and
      migration of human breast cancer cells ZR-75-30 was examined. The migration and
      invasive potential of ZR-75-30 cells were examined by wound-healing assays and
      matrigel invasion chamber assays. The adhesion to type IV collagen and laminin
      were evaluated by MTT assay. The expression and proteinase activity of two matrix
      metalloproteinases (MMPs), matrix metalloproteinases 2 (MMP-2) and matrix
      metalloproteinases 9 (MMP-9), were analyzed by Western blot analysis and gelatin
      zymography, respectively. RESULTS: HMQ1611 effectively inhibited ZR-75-30 cell
      invasion and significantly suppressed adhesion to type IV collagen and laminin
      coated substrate in a dose-dependent manner. Western blot and gelatin zymography
      analysis showed that HMQ1611 significantly inhibited the expression and secretion
      of MMP-2 and MMP-9 in ZR-75-30 cells. Additionally, treatment of ZR-75-30 cells
      with HMQ1611 downregulated the expression of MMP-2 and MMP-9. CONCLUSIONS:
      HMQ1611 had potential to suppress the adhesion, migration and invasion of ZR-75
      30 cancer cells, and it could serve as a potential novel therapeutic candidate
      for the treatment of metastatic breast cancer.

PMID- 22875643
TI  - Is a "Merkel" just like a melanoma? The pathologic analysis of Merkel cell
      carcinoma specimens.

PMID- 22875644
TI  - Is restaging with chest and abdominal CT scan after neoadjuvant chemoradiotherapy
      for locally advanced rectal cancer necessary?
AB  - BACKGROUND: There is no evidence regarding restaging of patients with locally
      advanced rectal cancer after a long course of neoadjuvant radiotherapy with or
      without chemotherapy. This study evaluated the value of restaging with chest and
      abdominal computed tomographic (CT) scan after radiotherapy. METHODS: Between
      January 2000 and December 2010, all newly diagnosed patients in our tertiary
      referral hospital, who underwent a long course of radiotherapy for locally
      advanced rectal cancer, were analyzed. Patients were only included if they had
      chest and abdominal imaging before and after radiotherapy treatment. RESULTS: A
      total of 153 patients who met the inclusion criteria and were treated with
      curative intent were included. A change in treatment strategy due to new findings
      on the CT scan after radiotherapy was observed in 18 (12%) of 153 patients.
      Twelve patients (8%) were spared rectal surgery due to progressive metastatic
      disease. CONCLUSIONS: Restaging with a chest and abdominal CT scan after
      radiotherapy for locally advanced rectal cancer is advisable because additional
      findings may alter the treatment strategy.

PMID- 22875645
TI  - Minimally invasive inguinal lymph node dissection (MILND) for melanoma:
      experience from two academic centers.
AB  - BACKGROUND AND AIM: Regional lymph nodes are the most frequent site of spread of
      metastatic melanoma. Operative intervention remains the only potential for cure,
      but the reported morbidity rate associated with inguinal lymphadenectomy is
      approximately 50%. Minimally invasive lymph node dissection (MILND) is an
      alternative approach to traditional, open inguinal lymph node dissection (OILND).
      The aim of this study is to evaluate our early experience with MILND and compare
      this with our OILND experience. METHODS: We conducted a prospective study of 13
      MILND cases performed for melanoma from 2010 to 2012 at two tertiary academic
      centers. We compared our outcomes with retrospective data collected on 28 OILND
      cases performed at the same institutions, by the same surgeons, between 2002 and
      2011. Patient characteristics, operative outcomes, and 30-day morbidity were
      evaluated. RESULTS: Patient characteristics were similar in the two cohorts with
      no statistically significant differences in patient age, gender, body mass index,
      or smoking status. MILND required longer operative time (245 vs 138 min,
      p=0.0003). The wound dehiscence rate (0 vs 14%, p=0.07), hospital readmission
      rate (7 vs 21%, p=0.25), and hospital length of stay (1 vs 2 days, p=0.01) were
      all lower in the MILND group. The lymph node count was significantly higher (11
      vs 8, p=0.03) for MILND compared with OILND. CONCLUSIONS: MILND for melanoma is a
      novel alternative to OILND, and our preliminary data suggest that MILND provides
      an equivalent lymphadenectomy while minimizing the severity of postoperative
      complications. Further research will need to be conducted to determine if the
      oncologic outcomes are similar.

PMID- 22875646
TI  - Papillary thyroid carcinoma in pregnancy: a variant of the disease?
AB  - BACKGROUND: There are conflicting reports in the literature regarding the
      prognostic influence of pregnancy on patients with papillary thyroid carcinoma
      (PTC), and there is no literature on specific microRNA (miRNA) profiles of PTC in
      the context of pregnancy. We aim to examine clinically if pregnancy is an adverse
      factor in PTC, and if pregnancy-associated PTC are biologically different from
      those in nonpregnant women in terms of their miRNA profiles. METHODS: Women
      diagnosed with PTC during or soon after pregnancy were recruited into the
      pregnancy group. Age-matched nonpregnant females were recruited into the
      nonpregnancy group. MiRNA microarray was performed on PTC tissue of pregnant
      patients (10), nonpregnant patients (10), and normal thyroids (5). There were 6
      differentially expressed miRNAs from the microarray comparisons validated with RT
      PCR. RESULTS: There were 24 patients in the clinical pregnancy group and 30 in
      the nonpregnancy group. Tumors from the pregnancy group were significantly larger
      and showed more regional lymph node metastases. The microarray data showed a
      total of 27 miRNAs that were potential differentiators of PTC tissue samples from
      pregnant and nonpregnant patients. Of the 6 selected for validation, no
      significant difference in expression was found. CONCLUSIONS: Our clinical data
      suggests that PTC during pregnancy may be more locoregionally aggressive.
      However, no difference in survival or recurrence is demonstrated. The miRNA
      profiles of the pregnancy-associated PTC have not been shown to be different to
      the nonpregnancy counterparts. This likely suggests that the differences seen
      clinically are related to patient factors rather than the disease itself.

PMID- 22875647
TI  - Treating patients with colon cancer liver metastasis: a nationwide analysis of
      therapeutic decision making.
AB  - BACKGROUND: Criteria for resectability of colon cancer liver metastases (CLM) are
      evolving, yet little is known about how physicians choose a therapeutic strategy
      for potentially resectable CLM. METHODS: Physicians completed a national Web
      based survey that consisted of varied CLM conjoint tasks. Respondents chose among
      three treatment strategies: immediate liver resection (LR), preoperative
      chemotherapy followed by surgery (C -> LR), or palliative chemotherapy (PC). Data
      were analyzed by multinomial logistic regression, yielding odds ratios (OR).
      RESULTS: Of 219 respondents, 79 % practiced at academic centers and 63 % were in
      practice >=10 years. Median number of cases evaluated was four per month.
      Surgical training varied: 51 % surgical oncology, 44 % hepato-pancreato
      biliary/transplantation, 5 % no fellowship. Although each factor affected the
      choice of CLM therapy, the relative effect differed. Hilar lymph node disease
      predicted a strong aversion to LR with surgeons more likely to choose C -> LR (OR
      8.92) or PC (OR 49.9). Solitary lung metastasis also deterred choice of LR, with
      respondents favoring C -> LR (OR 4.43) or PC (OR 6.97). After controlling for
      clinical factors, surgeons with more years in practice were more likely to choose
      PC over C -> LR (OR 1.94) (P = 0.005). Surgical oncology-trained surgeons were
      more likely than hepatobiliary/transplant-trained surgeons to choose C -> LR (OR
      2.53) or PC (OR 4.15) (P < 0.001). CONCLUSIONS: This is the first nationwide
      study to define the relative impact of key clinical factors on choice of therapy
      for CLM. Although clinical factors influence choice of therapy, surgical
      subspeciality and physician experience are also important determinants of care.

PMID- 22875648
TI  - Fear of cancer recurrence after curative pancreatectomy: a cross-sectional study
      in survivors of pancreatic and periampullary tumors.
AB  - BACKGROUND: Fear of disease recurrence is well documented among cancer survivors,
      but its significance among patients treated for solid pancreatic and
      periampullary neoplasms is unknown despite the known risk of recurrence
      associated with these tumors. We hypothesized that fear of cancer recurrence
      (FCR) represents a common source of psychosocial distress in this population and
      sought to characterize subgroups for whom FCR might represent a target for
      intervention to improve quality of life. METHODS: We conducted a cross-sectional
      study of FCR in patients who were disease-free after potentially curative
      pancreatectomy for ductal or periampullary adenocarcinoma or pancreatic
      neuroendocrine tumor. We assessed seven discrete dimensions of FCR using the Fear
      of Recurrence Inventory and evaluated quality of life and psychosocial distress
      using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire and
      the Hospital Anxiety and Depression Scale. RESULTS: Of 354 eligible patients, 240
      (68 %) participated in the study a median of 48 months after potentially curative
      pancreatectomy. An FCR severity score indicative of frequent fearful thoughts,
      emotional disturbance and functional impairment was identified in 37, 28, and 35
      % of patients with pancreatic adenocarcinoma, nonpancreatic periampullary
      adenocarcinoma, and pancreatic neuroendocrine tumor, respectively. Anxiety (P <
      0.001) and low quality of life (P = 0.028) were independently associated with a
      clinically significant level of FCR, but histopathologic diagnosis and
      clinicopathologic markers of prognosis were not. CONCLUSIONS: FCR represents a
      significant concern for one-third of patients after curative surgery for a
      pancreatic or periampullary tumor, regardless of their actual likelihood of
      recurrence or disease-related death.

PMID- 22875649
TI  - Effect of ASCO/CAP guidelines for determining ER status on molecular subtype.
AB  - BACKGROUND: Determination of estrogen receptor (ER), progesterone receptor (PR),
      and human epidermal growth factor receptor 2 (HER2) status is standard for
      predicting prognosis and determining treatment options for patients with breast
      cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of
      American Pathologists (CAP) issued guidelines that tumors with >=1% positively
      staining cells should be considered ER positive. Here, we determined how this
      cutoff relates to molecular subtype. METHODS: Clinicopathological characteristics
      were compared between ER-negative, ER-positive, and low-ER-staining (1-10%)
      tumors using chi-square analysis with P<0.05 defining statistical significance.
      Gene expression data were generated for 26 low-ER-staining tumors, and their
      intrinsic subtype determined. Immunohistochemistry (IHC)-defined surrogate
      subtypes, using the threshold of positivity defined by ASCO/CAP guidelines, were
      compared with molecular subtypes. RESULTS: Low-ER-staining tumors were
      clinicopathologically more similar to ER-negative than to ER-positive tumors; 88%
      of low-staining tumors were basal like or HER2 enriched. Only those tumors
      expressing 10% ER-positive cells were classified as luminal A subtype.
      CONCLUSIONS: Under ASCO/CAP guidelines, tumors with 1-10% ER staining would be
      classified as ER positive, yet most are basal like or HER2 enriched and have
      pathological features similar to ER-negative tumors. Clinical trials seeking to
      treat tumors of ER-negative basal-like and/or HER2-enriched subtypes should thus
      not preclude enrollment based solely on results of ER immunohistochemistry. As ER
      status is a critical element in the choice of treatments for patients with breast
      cancer, it is imperative that the most effective method for classifying tumors be
      developed.

PMID- 22875650
TI  - Sorafenib for non-selected patient population with advanced hepatocellular
      carcinoma: efficacy and safety data according to liver function.
AB  - OBJECTIVE: Sorafenib is the standard treatment of patients with advanced
      hepatocellular carcinoma, regardless of the liver functional reserve. We present
      a single institutional series of Child-Pugh A and Child-Pugh B patients treated
      with sorafenib with the aim to establish the efficacy and safety of sorafenib in
      patients of daily clinical conditions and to compare these results between Child
      Pugh A and Child-Pugh B patients. MATERIALS AND METHODS: A total of 51 patients
      were treated with sorafenib 400 mg/12 h until disease progression or unacceptable
      toxicity. RESULTS: The median progression-free survival and overall survival for
      the overall population were 3.5 and 8.2 months, respectively, with a 1-year
      survival rate of 27 %. Overall survival was significantly longer for patients
      Child-Pugh A compared with those with Child-Pugh B liver function (8.7 vs. 4.7
      months, respectively). The most common adverse events were fatigue (62.7 %),
      diarrhea (58 %), hypertension (31.3 %), and hand-foot syndrome (31.3 %), and in
      most cases grade 1 or 2 according to the NCI-CTC 3.0. Grade 4 liver-related
      events occurred mainly in Child-Pugh B patients with decompensated cirrhosis at
      the time of sorafenib initiation (54.5 % of that group). DISCUSSION: The benefit
      of sorafenib in Child-Pugh B patients, if exist, may be limited by frequent liver
      related events, especially in decompensated patients, and then, toxicity and
      impact in quality of life should be carefully monitored.

PMID- 22875651
TI  - Health related quality of life in Mexican women with systemic lupus
      erythematosus: a descriptive study using SF-36 and LupusQoL(C).
AB  - The LupusQoL(c) questionnaire is a disease-specific health related quality of
      life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The
      Short Form-36 (SF-36) is a generic instrument that captures the physical,
      psychological, and social impact. We conducted a descriptive study of women aged
      >= 18 years attending our Lupus Clinic. HRQOL was assessed by applying the
      LupusQoL(c) and SF-36. Lupus activity was measured using the Mexican Systemic
      Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using
      the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed
      using descriptive statistics, the chi-square test and Pearson's product moment
      correlation coefficient. A total of 127 patients were included with a mean age of
      40.5 +/- 12.6 years. The mean disease duration was 8.2 +/- 5.6 years, the mean
      disease activity score was 2.4 +/- 3.0, and the mean SDI score 0.77 +/- 1.06. The
      mean SF-36 score was 58.1 +/- 21.1 and the mean LupusQoL(c) score was 69 +/-
      22.7. The correlation between global scores of the SF-36 and LupusQoL(c) was rho
      = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36
      and the LupusQoL(c) was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively.
      The correlation between the SDI and the SF-36 and the LupusQoL(c) was -0.28 (p =
      0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL(c) and
      SF-36 were useful instruments in assessing HRQOL in Mexican lupus female
      patients. The usefulness of the LupusQoL(c) should be evaluated in lupus patients
      with moderate to severe disease activity.

PMID- 22875652
TI  - A pilot study of office-based spirometry in patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: Although pulmonary involvement is common in systemic lupus
      erythematosus (SLE), its effects on healthy lifestyle physical activity and its
      association with fatigue have not been well characterized. The goals of this
      study were to describe pulmonary function measured by office-based spirometry in
      patients with SLE and to compare spirometry with physical activity and systemic
      fatigue. METHODS: During an office visit, 49 patients with SLE completed
      spirometry assessing: a) forced expiratory volume in 1 s (FEV(1), a measure of
      airway patency and responsiveness); b) forced vital capacity (FVC, a measure of
      lung volume); and c) maximum voluntary ventilation (MVV, a measure of volume of
      air moved during rapid breathing) which has been hypothesized to be decreased in
      SLE due to muscle fatigue. Patients also performed a 2-min corridor walking test
      and completed self-reported questionnaires measuring weekly physical activity and
      systemic fatigue. RESULTS: Mean age was 45 years, 45 (92%) were women, mean
      SLEDAI and SLICC scores were 2.8 and 1.0, respectively. Some 24 patients had a
      smoking history, and 15 had a history of SLE-related pleuritis, which was not
      active at enrollment. FEV(1) and FVC were 96% of predicted, but MVV was only 55%
      of predicted. The distance walked during the corridor test was similar to that of
      patients with other chronic diseases; however, self-reported physical activity
      was less than recommended by national guidelines. There were no associations
      between spirometry values and history of pleuritis, other pulmonary diagnoses, or
      smoking (p > .10 for all comparisons), however, better FEV(1) (p = .04) and
      better FVC (p = .04) were associated with more self-reported activity and better
      FEV(1) (p = .03) was associated with longer distance walked during the corridor
      test. Most patients reported marked systemic fatigue; however, there were no
      associations between spirometry values and fatigue scores (p > .10 for all
      comparisons). CONCLUSIONS: MVV was markedly diminished, which supports the
      hypothesis that SLE may be associated with respiratory muscle fatigue during
      rapid breathing. MVV was not associated with mild-to-moderate patient-directed
      physical activity; however, lower FEV(1) and FVC were associated with less self
      reported and performance-based physical activity.

PMID- 22875653
TI  - Semaphorin 3A - a marker for disease activity and a potential putative disease
      modifying treatment in systemic lupus erythematosus.
AB  - Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune
      responses and have a demonstrated effect on the course of collagen-induced
      arthritis. Sema3A was also found to be involved in other immune-mediated
      diseases, e.g. psoriasis and allergic rhinitis. In this review we concentrated on
      the involvement of sema3A and NP-1 in the pathogenesis of systemic lupus
      erythematosus (SLE) and on the specific effect of sema3A on the auto-reactive
      properties of B cells in SLE patients. We demonstrated the expression of sema3A
      in renal biopsies from lupus glomerulonephritis patients. This expression was
      found to be inversely correlated with proteinuria and kidney function tests.
      Sema3A serum levels in SLE patients were found to be significantly lower than in
      RA patients (disease control) and lower yet than in normal individuals. Altered
      serum sema3A levels were found to be in inverse correlation with SLE disease
      activity, mainly with renal damage and the presence of anti-cardiolipin
      antibodies. The expression of both sema3A and NP-1 on B cells from SLE patients
      was significantly different in comparison with normal healthy individuals.
      Finally, we demonstrated that when sema3A was co-cultured with CpG-ODN-stimulated
      memory B cells of SLE patients, their TLR-9 expression was significantly reduced
      by almost 50% (p = 0.001). These findings, along with the observation of sema3A
      being reduced in SLE patients in correlation with disease severity and
      autoimmunity, and memory B cells being beneficially responsive to sema3A, suggest
      this regulatory molecule may be considered as a potential therapy for SLE. Such
      focused therapies will help in achieving the maintenance of self-tolerance and
      alter pro-inflammatory status in lupus.

PMID- 22875654
TI  - Contortrostatin, a homodimeric disintegrin isolated from snake venom inhibits
      herpes simplex virus entry and cell fusion.
AB  - BACKGROUND: Herpes simplex virus (HSV) causes significant health problems from
      periodical skin and corneal lesions to encephalitis. HSV entry provides a unique
      opportunity for therapeutic intervention. In this study, we evaluated
      contortrostatin (CN), an Arg-Gly-Asp motif containing disintegrin isolated from
      snake venom, as a novel therapeutic agent with ability to block HSV entry and
      related membrane fusion. METHODS: In vitro efficacy of CN against HSV was
      determined using an HSV type-1 (HSV-1) entry assay based on the measurement of
      beta-galactosidase reporter activity originating from the genome of a recombinant
      strain of HSV-1(KOS) gL86. HSV-1 glycoprotein-mediated cell-to-cell fusion was
      used to study the effect of CN on polykaryocyte formation. Primary as well as
      transformed cell lines were used for this study. RESULTS: Pre-treatment of
      Chinese hamster ovary (CHO-K1) cells expressing HSV-1 glycoprotein D receptors
      and primary cultures of human corneal fibroblasts (CF) with CN resulted in the
      inhibition of entry, cell-to-cell fusion, and polykaryocyte formation.
      Interestingly, a more pronounced anti-HSV-1 effect was observed in naturally
      susceptible CF than CHO-K1 cells. CONCLUSIONS: CN, a novel venom-derived peptide,
      exhibits the ability to block two key steps, entry and cell-to-cell fusion, in
      HSV infection. Showing strong promise for development as an anti-HSV agent, it
      also demonstrates better prophylactic efficacy in primary cells.

PMID- 22875655
TI  - Intrauterine growth restriction decreases endochondral ossification and bone
      strength in female rats.
AB  - Intrauterine growth restriction (IUGR) modifications to postnatal skeletal growth
      may increase adult fracture, especially in females who have greater risk of
      osteoporosis. Little is known about the effect of IUGR on the patterns of
      postnatal endochondral ossification and bone development. Here for the first time
      we reveal bone formation, mineralization, and strength in IUGR female rats during
      early postnatal life and adulthood. Endochondral ossification rate of the
      hypertrophic zone (HZ) and hypertrophic cell length (HCL) at distal femur and
      proximal tibia, and primary ossification center (POC) of the whole femur and
      tibia were quantified at birth to day 21. Bone area (BA), bone mineral content
      (BMC), and bone density by dual-energy X-ray absorptiometry and bone strength
      determined from three-point bending were measured at days 21 and 120. IUGR femur
      and tibia HZ, HCL, and POC were significantly diminished at birth to day 21. IUGR
      decreased BA and BMC as well as femur/tibia diameter, length, stiffness, and peak
      load values at days 21 and 120. Our findings demonstrate a negative long-term
      effect of IUGR on bone size, mineral content, and strength in weanling and adult
      female rats. We speculate that IUGR decreases endochondral ossification
      responsiveness, and in turn, postnatal linear skeletal growth, mineralization,
      and strength in female rats.

PMID- 22875656
TI  - Assessing cardiovascular disease risk among young women with a history of
      delivering a low-birth-weight infant.
AB  - OBJECTIVE: To assess the prevalence and risk factors of cardiovascular disease
      (CVD) among younger women by pregnancy history. METHODS: Cross-sectional study
      using 1999 to 2006 National Health and Nutrition Examination Survey including
      women aged 20 to 64 years who had delivered at least one infant (n = 4820). Women
      self-reported pregnancy history and a clinician diagnosed CVD; CVD risk factors
      included hypertension (mean systolic blood pressure [BP] >=140 mm Hg or mean
      diastolic BP >=90 mm Hg, or currently treated), high cholesterol (total
      cholesterol >=240 mg/dL or currently treated), diabetes (self-report or
      hemoglobin A1c >=6.5), and smoking (self-report or cotinine-verified).
      Multivariable logistic regression was used to assess the association between
      pregnancy history and CVD. RESULTS: Of the women we studied, 4.6% had CVD; 3.1%
      had delivered a term low-birth-weight infant (TLBWI). Women with a history of
      TLBWI had an adjusted odds ratio (AOR) of 2.07 (95% confidence intervals [CI]
      1.08 to 3.99) for CVD compared with women without a history of LBWI. Adjustment
      for hypertension and high cholesterol mildly attenuated the association (AOR
      1.85, 95% CI 0.89 to 3.83). Among women without CVD (n = 4555), 23.1% with a
      history of TLBWI had two risk factors compared with 14.0% of those without a
      history of LBWI (p = 0.0016). CONCLUSION: Women with a history of TLBWI should be
      informed of a possible increased risk of CVD and encouraged to receive screenings
      as recommended.

PMID- 22875657
TI  - Association of maternal vitamin D and placenta growth factor with the diagnosis
      of early onset severe preeclampsia.
AB  - OBJECTIVE: Decreased maternal 25-hydroxyvitamin D (25-OH-D) and placenta growth
      factor (PlGF) have both been associated with the diagnosis of early onset severe
      preeclampsia (EOSPE). This investigation aimed to define the association of these
      biomarkers with EOSPE. STUDY DESIGN: Patients with EOSPE (n = 40) and healthy
      controls (n = 40) were recruited and information on demographics, outcomes, and
      plasma was collected at diagnosis of EOSPE or gestational age-matched controls.
      25-OH-D was assessed by radioimmunoassay and reported in nanogram per milliliter.
      PlGF was assessed by enzyme-linked immunosorbent assay and reported in picogram
      per milliliter. Kruskal-Wallis test was used to compare biomarkers between
      groups. Multivariable logistic regression was used to determine associations
      between 25-OH-D or PlGF and the diagnosis of EOSPE. RESULTS: In EOSPE, both 25-OH
      D and PlGF were decreased significantly compared with controls. After controlling
      for age, race, body mass index, and gestational age at sample collection, both 25
      OH-D (adjusted odds ratio 0.14 [0.05, 0.36]) and PlGF (adjusted odds ratio 0.03
      [0.01, 0.24] were significantly associated with diagnosis of ESOPE (p < 0.001 for
      both markers). CONCLUSION: PlGF and 25-OH-D are both associated with the
      diagnosis of EOSPE. These biomarkers may be helpful in development of novel rapid
      diagnostic tests for preeclampsia.

PMID- 22875658
TI  - The effect of phototherapy on fecal calprotectin levels.
AB  - OBJECTIVE: Fetal calprotectin levels increase in the early stages of necrotizing
      enterocolitis. Although the effects of several factors on fetal calprotectin have
      been studied, the effect of phototherapy is not known. In this study, we analyzed
      the effect of phototherapy on fetal calprotectin levels. METHODS: Ninety breast
      fed newborns (46 male, 44 female) who were hospitalized for indirect
      hyperbilirubinemia and treated with phototherapy were included to the study.
      Forty-two of them were term and 44 of them were preterm. Newborns treated with
      phototherapy (n = 53) constituted the phototherapy group (29 preterm, 24 term)
      and 37 newborns who did not receive phototherapy (19 preterm, 18 term)
      constituted the control group. Fecal samples were collected 24 hours after
      phototherapy had been started. Fecal samples (100 mg) were weighed with sensitive
      scales and preserved at -80 degrees C after buffering with a special solution.
      All samples were studied at the same time with a fecal calprotectin kit by using
      enzyme-linked immunosorbent assay. RESULTS: There were no statistically
      significant difference between fecal calprotectin levels of term and preterm
      babies who received phototherapy and babies who did not receive phototherapy.
      CONCLUSION: There was no effect of 24-hour phototherapy on fecal calprotectin
      levels in preterm and term newborns.

PMID- 22875659
TI  - Kidney injury molecule-1 as a promising biomarker for acute kidney injury in
      premature babies.
AB  - OBJECTIVE: To evaluate the role of urinary kidney injury molecule-1 (uKIM-1) in
      early determination of renal injury in premature infants with respiratory
      distress syndrome (RDS). STUDY DESIGN: Forty-eight premature babies hospitalized
      in the neonatal intensive care unit were included in the study and divided into
      three groups: group I, healthy premature infants; group II, preterm infants with
      RDS without acute kidney injury (AKI); group III, preterm infants with RDS and
      AKI. uKIM-1 and creatinine along with serum creatinine levels were measured with
      enzyme-linked immunosorbent assay on days 1, 3, and 7 of life. RESULTS: On day 1,
      uKIM-1 levels in babies with RDS and AKI were higher than the other two groups.
      In this group, a significant increase in uKIM-1 levels were detected on day 3 (p
      = 0.015). The sensitivity and specificity of uKIM-1 were calculated as 73.3% and
      76.9%, respectively, along with the increase of 0.5 ng per milligram of
      creatinine of uKIM-1 in day 3, when compared with values on day 1. Elevated uKIM
      1 on day 7 was found to increase the risk of death by 7.3 times. CONCLUSION:
      Serial uKIM-1 measurements can be used as a noninvasive indicator of kidney
      injury and uKIM-1 can be an ideal biomarker in premature infants.

PMID- 22875660
TI  - What about the Misgav-Ladach surgical technique in patients with previous
      cesarean sections?
AB  - OBJECTIVE: The Misgav-Ladach technique is recommended worldwide to perform
      cesarean sections but there is no consensus about the appropriate technique to
      use in patients with previous cesarean sections. This study evaluated the
      feasibility of the Misgav-Ladach technique in patients with previous cesarean
      sections. STUDY DESIGN: This prospective cohort study included all women
      undergoing cesarean section after 36 weeks of gestation over a 5-month period,
      with the Misgav-Ladach technique as first choice, whatever the previous number of
      cesarean sections. RESULTS: Among the 204 patients included, the Misgav-Ladach
      technique was successful in 100%, 80%, and 65.6% of patients with no, one, and
      multiple previous cesarean sections, respectively. When successful, the Misgav
      Ladach technique was associated with a shorter incision to birth interval in
      patients with no previous cesarean section compared with patients with one or
      multiple previous cesarean sections. Anterior rectus aponeurosis fibrosis and
      severe peritoneal adherences were the two main reasons explaining the Misgav
      Ladach technique failure. CONCLUSION: The Misgav-Ladach technique is possible in
      over three-fourths of patients with previous cesarean sections with a slight
      increase in incision to birth interval compared with patients without previous
      cesarean section. Further studies comparing the Misgav-Ladach and the
      Pfannenstiel techniques in women with previous cesarean should be done.

PMID- 22875661
TI  - Skin closure of pfannenstiel incision with dermabond, staples, or suture during
      cesarean delivery: experience of a single attending.
AB  - OBJECTIVE: We aimed to compare the rates of wound separation (WS) and surgical
      site infection (SSI) after cesarean delivery (CD) by a single surgeon.
      Pfannenstiel skin incision (PSI) was closed with Dermabond, staples, or suture.
      STUDY DESIGN: Retrospectively all women having CD via PSI were identified. WS and
      SSI rates with Dermabond were compared with other two techniques. RESULTS: Of 239
      CDs performed, 88% (n = 211) were available for postpartum evaluation. The PSI
      was closed with Dermabond in 85 (40%), staples in 76 (36%), and suture in 50
      (24%). Overall WS rate was 7%; with Dermabond, it was 5% versus 13% with staple
      (p = 0.090) and 2% with suture (p = 0.651). Post hoc calculation suggests a
      randomization of 4325 women is needed to determine if Dermabond has one-third
      less wound complication than suture. CONCLUSION: For the PSI closure, Dermabond
      may be a useful alternative skin closure device, though a randomized trial is
      warranted.

PMID- 22875662
TI  - Cerclage pessary for preventing preterm birth in women with a singleton pregnancy
      and a short cervix at 20 to 24 weeks: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of cerclage pessary in the prevention
      of preterm birth in asymptomatic Chinese women with a short cervix at 20 to 24
      weeks. METHODS: Low-risk women carrying singleton pregnancies were screened with
      transvaginal ultrasound, and those with a cervical length <25 mm at 20 to 24
      weeks were recruited into a randomized controlled trial, comparing the
      prophylactic use of cerclage pessary with expectant management. The analysis was
      by intent-to-treat. The primary outcome measure was preterm delivery before 34
      weeks. RESULTS: Among 4438 screened women, 203 women (4.6%) met the inclusion
      criteria and 108 (58%) consented for the study. A total of 53 and 55 women were
      allocated to pessary and control groups, respectively. There was no difference in
      background demographics, including the mean cervical length (19.6 mm versus 20.5
      mm) and the mean gestational age at randomization (both 21.9 weeks). Delivery
      before 34 weeks occurred in 9.4% and 5.5% (p = 0.46) in the pessary and the
      control groups, respectively. No differences in major side effects were noted
      between the groups. CONCLUSION: In our population, <5% had a cervical length of
      less than 25 mm at 20 to 24 weeks' gestation. The prophylactic use of cerclage
      pessary did not reduce the rate of preterm delivery before 34 weeks.

PMID- 22875664
TI  - Measuring the angle of the subpubic arch using three-dimensional transperineal
      ultrasound scan: intraoperator repeatability and interoperator reproducibility.
AB  - OBJECTIVE: A method of measuring the subpubic arch angle using three-dimensional
      transperineal ultrasound scan (3DTUS) was developed, and the intraoperator
      repeatability and interoperator reproducibility were investigated. STUDY DESIGN:
      Using 3DTUS, volume data sets were obtained from the nine nulliparous pregnant
      women by three operators (A, B, and C) in each of the three study sessions. With
      volume reconstruction, a plane along the inferior edges of bilateral inferior
      pubic rami was obtained on the axial section. The angle made between the
      innermost points of both inferior pubic rami at the level of urethra and the
      inferoposterior point of symphysis pubis was measured as the subpubic arch angle.
      The intraoperator repeatability of the experienced operator (A) and the
      interoperator reproducibility between A, B, and C were assessed by the
      repeatability coefficient and the interoperator intraclass correlation (ICC),
      respectively. RESULTS: A total of 27 women were examined. The intraoperator
      repeatability was 4.73 degrees. The overall interoperator ICC was 0.860, and
      increased from 0.794 in the first session to 0.945 in the third session.
      CONCLUSION: With 3DTUS, it is feasible to measure subpubic arch angle with
      satisfactory intraoperator repeatability and interoperator reproducibility. This
      easy-to-learn technique extends the possibilities of future pelvimetry research
      using 3DTUS.

PMID- 22875663
TI  - Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a
      preterm labor tocolytic.
AB  - OBJECTIVE: To characterize the pharmacokinetics and pharmacogenetics of
      nifedipine in pregnancy. STUDY DESIGN: Pregnant women receiving oral nifedipine
      underwent steady-state pharmacokinetic testing over one dosing interval. DNA was
      obtained and genotyped for cytochrome P450 (CYP) 3A5 and CYP3A4*1B. Nifedipine
      and oxidized nifedipine concentrations were measured in plasma, and
      pharmacokinetic parameters were compared between those women who expressed a
      CYP3A5*1 allele and those who expressed only variant CYP3A5 alleles (*3,*6, or
      *7). RESULTS: Fourteen women had complete data to analyze. Four women (29%)
      expressed variant CYP3A5; three of these women were also CYP3A4*1B allele
      carriers. The mean half-life of nifedipine was 1.68 +/- 1.56 hours. The area
      under the curve from 0 to 6 hours for the women receiving nifedipine every 6
      hours was 207 +/- 138 ug.h /L. Oral clearance was different between high
      expressers and low expressers (232.0 +/- 37.8 ug/mL versus 85.6 +/- 45.0 ug/mL,
      respectively; p = 0.007). CONCLUSION: CYP3A5 genotype influences the oral
      clearance of nifedipine in pregnant women.

PMID- 22875665
TI  - Porphyromonas gingivalis LPS stimulation downregulates DNMT1, DNMT3a, and JMJD3
      gene expression levels in human HaCaT keratinocytes.
AB  - OBJECTIVE: The role of epigenetic regulation in inflammatory diseases such as
      periodontitis is poorly known. The aim of this study was to assess whether
      Porphyromonas gingivalis lipopolysaccharide (LPS) can modulate gene expression
      levels of the some enzymes that promote epigenetic events in cultures of the
      human keratinocytes and gingival fibroblasts. In addition, the same enzymes were
      evaluated in gingival samples from healthy and periodontitis-affected
      individuals. MATERIALS AND METHODS: Primary gingival fibroblast and keratinocyte
      (HaCaT) cultures were treated with medium containing P. gingivalis LPS or P.
      gingivalis LPS vehicle for 24 h. After this period, cell viability was assessed
      by MTT test and total RNA extracted to evaluate gene expression levels of the
      following enzymes by qRT-PCR: DNA methyltransferase 1 (DNMT1), DNA
      methyltransferase 3a (DNMT3a), histone demethylases Jumonji domain containing 3
      (JMJD3) and ubiquitously transcribed tetratricopeptide repeat, X chromosome
      (UTX). To evaluate gene expression in healthy and periodontitis-affected
      individuals, total RNA was extracted from biopsies of gingival tissue from
      healthy and periodontitis sites, and gene expression of DNMT1, DNAMT3a, JMJD3,
      and UTX was evaluated by qRT-PCR. RESULTS: No significant differences were found
      in the gene expression analysis between healthy and periodontitis-affected
      gingival samples. The results showed that LPS downregulated DNMT1 (p < 0.05),
      DNMT3a (p < 0.05), and JMJD3 (p < 0.01) gene expression in HaCaT cells, but no
      modulation was observed in gingival fibroblasts. CONCLUSION: P. gingivalis LPS
      exposure to human HaCaT keratinocytes downregulates gene expression of the
      enzymes that promote epigenetic events. CLINICAL RELEVANCE: The advance knowledge
      about epigenetic modifications caused by periodontopathogens may to possibly led
      to the development of new periodontal therapies.

PMID- 22875666
TI  - Radioprotection to small intestine of the mice against ionizing radiation by
      semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1.
AB  - Ionizing irradiation induces severe damage to the intestinal crypt cells which
      are responsible for renovation and maintenance of the intestinal cellular
      architecture. Therefore, protection of intestinal cells and tissue against lethal
      irradiation using a semiquinone glucoside derivative (SQGD) isolated from
      radioresistant bacterium Bacillus sp. INM-1 is the prime focus of the present
      investigation. BALB/c mice were administered by SQGD (50 mg/kg.b.wt. i.p.) 2 h
      before whole body irradiation (10 Gy), and histological analysis of the jejunum
      section was carried out and compared to the irradiated mice. Significant (p <
      0.0001) increase in villus length, number of cells per villus, crypts numbers per
      villus section, total cells counts and mitotic cell counts per crypt and low
      goblet cells per villus section, and low apoptotic index per crypt section were
      observed in the irradiated mice pre-treated by SQGD at 48-168 h. Significant
      induction in NF-kbeta at 24 h and Bcl-2/Bax ratio was observed in irradiated mice
      pre-treated by SQGD compared to only irradiated animals. SQGD pre-treatment
      before irradiation was found instrumental to reverse the radiation-induced
      degenerative changes by replenishment of the damaged cells by enhancing mitotic,
      proliferating, pro-survival, and apoptosis inhibitory activities probably through
      modulation of cell cycle arrest in G(1)/S phase in the intestinal cellular
      milieu.

PMID- 22875668
TI  - The biology of Echinoparyphium (Trematoda, Echinostomatidae).
AB  - Echinoparyphium species are common, widely distributed intestinal parasites
      causing disease in animals worldwide. Intermediate hosts include snails,
      bivalves, and fish, whereas the definitive hosts are mainly birds and mammals.
      This review examines the significant literature on Echinoparyphium. Descriptive
      studies, life cycle, experimental and manipulative studies, and biochemical and
      molecular studies are presented. The influence of environmental factors, and
      toxic pollutants, are reviewed as well as studies on the pathology of
      Echinoparyphium.

PMID- 22875667
TI  - Mechano growth factor (MGF) promotes proliferation and inhibits differentiation
      of porcine satellite cells (PSCs) by down-regulation of key myogenic
      transcriptional factors.
AB  - Porcine satellite cells represent an ideal model system for studying the cellular
      and molecular basis regulating myogenic stem cell proliferation and
      differentiation and for exploring the experimental conditions for myoblast
      transplantation. Here, we investigated the effects of mechano growth factor
      (MGF), a spliced variant of the IGF-1 gene, on porcine satellite cells. We show
      that MGF potently stimulated proliferation while inhibited differentiation of
      porcine satellite cells. MGF-treatment acutely down-regulates the expression of
      myogenic determination factor (MyoD) and the cyclin-dependent kinase inhibitor
      p21. MGF-treatment also markedly reduced the overall expression of cyclin B1 and
      key factors of the myogenic regulatory and myocyte enhancer families, including
      Myogenein and MEF2A. Taken together, the gene expression data from MGF-treated
      porcine satellite cells are in favor of a molecular model in which MGF inhibits
      porcine satellite cell differentiation by down-regulating either the activity or
      expression of MyoD, which, in turn, suppresses the expression of key genes
      required for cell cycle progression and differentiation, such as p21, Myogenin,
      and MEF2. Overall, our findings are in support of the previous suggestion that
      MGF may be used in vivo and in vitro to promote proliferation of myogenic stem
      cells to prevent and treat age-related muscle degenerative diseases.

PMID- 22875669
TI  - Axenic cultivation and comparative phospholipase A2 activity of Giardia
      duodenalis in a serum-free medium.
AB  - Mammalian serum is essential for the growth of Giardia duodenalis cultivated
      under axenic conditions. Unfortunately, some factors present in bovine serum used
      as supplement in the culture medium may inhibit protozoal growth and activity.
      TYI-33-PACSR is a TYI medium supplemented with a serum replacement (PACSR) made
      up of Earle's amino acid solution, Diamond's vitamin-tween 80 mixtures and LCR (a
      lipid-cholesterol - rich mixture). PACSR was previously used in the culture media
      for axenic cultivation of Entamoeba histolytica and Trichomonas vaginalis. The
      main objective of this work was to demonstrate that TYI-33-PACSR is useful for
      axenic cultivation of G. duodenalis. Additionally, the activity of phospholipase
      A(2) (PLA A(2)) in the sub-cellular vesicular fraction (P30) of G. duodenalis
      grown in TYI-S-33 and TYI-33-PACSR was compared. All strains of Giardia grown in
      TYI-33-PACSR reached relative cellular densities of 91 to 95% compared to
      controls growing in serum-supplemented TYI-S-33 medium. Additionally, PLA A(2)
      activity was similar in the P30 sub-cellular fraction obtained from trophozoites
      growing in TYI-S-33 and TYI-33-PACSR. Thus, TYI-33-PACSR could be useful in
      analyzing the biological properties of G. duodenalis in the absence of serum.

PMID- 22875670
TI  - Menzbieria chalcographi, a new neogregarine pathogen of the great spruce bark
      beetle, Dendroctonus micans (Kugelann) (Curculionidae, Scolytinae).
AB  - This study concerns a new neogregarine parasitic in the great spruce bark beetle
      Dendroctonus micans (Kugelann) (Curculionidae, Scolytinae). The rate of infection
      was high, reaching 27.3%. There was no difference in the rate of infection of
      male and female beetles. The life-cycle stages of the pathogen were described by
      light and electron microscopy. Each gametocyst of the neogregarine included 8-16
      actinocephalid oocysts measuring 11.19 +/- 0.42 * 4.99 +/- 0.25 MUm. The
      described pathogen has the typical characteristics of members of the genus
      Menzbieria within the order Neogregarinida and it was identified as Menzbieria
      chalcographi. This is the first record of an infection of D. micans by M.
      chalcographi. Possibly, this pathogen could be useful for the biological control
      of this destructive bark beetle.

PMID- 22875671
TI  - Occurrence of blood parasites and intensity of infection in Prunella modularis in
      the montane and subalpine zone in the Slovak Carpathians.
AB  - The objective of this study was to obtain primary information on the occurrence
      of blood parasites and intensity of infection in the Dunnock Prunella modularis
      in the montane region of Slovakia. Altogether 109 birds were examined during the
      years 2006-2010. The occurrence of Haemoproteus sp., Leucocytozoon fringillinarum
      and Trypanosoma sp. was documented. Blood parasite prevalences of 45% by
      microscopic examination and 55% by PCR diagnostics were found. The prevalence of
      Leucocytozoon sp. was found to be dependent on host sex with males showing a
      significantly higher intensity of infection with Leucocytozoon. Adult birds
      showed significantly higher infection prevalence than subadults. The prevalences
      of both Leucocytozoon sp. and Haemoproteus sp. were significantly dependent on
      bird age. The intensity of infection with Haemoproteus and Leucocytozoon was
      positively correlated and higher intensity of infection was confirmed in adult
      birds then in subadults birds. The prevalence of blood parasites in our samples
      was significantly higher in comparison to most other studies from different
      countries of Europe conducted at lower altitudes, indicating that the montane
      zone is especially favourable for the transmission of Leucocytozoon and
      Haemoproteus species.

PMID- 22875672
TI  - Status of lipid peroxidation and antioxidant enzymes in goats naturally infected
      with Babesia ovis.
AB  - This study aimed to assess lipid peroxidation and antioxidant enzymes in goats
      naturally infected with Babesia ovis. Red blood cell count (RBC), hemoglobin (Hb)
      concentration, packed cell volume (PCV), malondialdehyde (MDA) concentration,
      erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase
      (CAT) activities and total antioxidant capacity (TAC) were determined in 15 goats
      naturally infected with B. ovis as well as same number of healthy goats. The
      parasitological diagnosis was confirmed using polymerase chain reaction (PCR)
      analysis by amplifying a partial 18S rRNA gene sequence of B. ovis. Percentage of
      parasitemia varied from 0.01 to 1%. The activities of erythrocyte GSH-Px, SOD,
      CAT and TAC were significantly lower (p<0.05) in the infected goats than in
      healthy ones. MDA concentration in erythrocytes of infected goats was
      significantly higher in infected goats than in healthy ones (p<0.05). Severity of
      parasitemia showed a positive correlation with the MDA and negative correlation
      with PCV, SOD, CAT, GSH-Px and TAC. Also, MDA was negatively correlated with PCV,
      SOD, CAT, GSH-Px and TAC. The results of this study suggested that oxidative
      damage to RBCs may contribute to the pathogenesis of anemia in caprine
      babesiosis.

PMID- 22875673
TI  - Ultrastructure of the vitellarium in the digeneans Phyllodistomum angulatum
      (Plagiorchiida, Gorgoderidae) and Azygia lucii (Strigeida, Azygiidae).
AB  - Fine structural features of the vitellarium of two digeneans, Phyllodistomum
      angulatum and Azygia lucii, are documented and compared with those of other
      digenean species. The cytodifferentiation of immature vitelline cells
      (vitellocytes) assumes the production and subsequent accumulation in their
      cytoplasm of several inclusions. Mature vitelline cells of P. angulatum are
      characterized by the presence of vitelline clusters (~2.7 MUm in diameter, with
      ~100 vitelline globules of ~0.35 MUm in diameter) and osmiophobic, saturated
      lipid droplets (~2-3 MUm in diameter), and in A. lucii vitelline clusters of the
      same diameter include much fewer vitelline globules (~50 globules of ~0.5 MUm in
      diameter), osmiophilic lipid droplets and alpha-glycogen. In both P. angulatum
      and A. lucii, interstitial cells are also present within the vitellarium. Two
      types of contact sites (septate and tight junctions) between adjoining
      interstitial cells also occur in both digenean species. Judging from the present
      and previous ultrastructural studies, it is suggested that there are three
      potential discriminatory characters of the digenean vitellarium (the number of
      different types of cell components within the vitellarium, the presence and type
      of junctional complexes between these cells, and the isolation of the vitellarium
      from the surrounding tissue) which may prove useful for a better understanding of
      the biology and evolutionary history of the different digenean groups.

PMID- 22875674
TI  - A review of the Lepocreadiidae (Digenea, Lepocreadioidea) from fishes of the
      waters around New Caledonia.
AB  - The lepocreadiid fauna of New Caledonia is reported and discussed and a new
      species and several new host and locality records presented. Hypoporus plataxi
      sp. nov. from Platax teira is described and distinguished from its only congener
      by its terminal genitalia, the structure of the anterior part of the alimentary
      system and other morphological features. New host and locality records and a
      description are given of Lepotrema cf. clavatum Ozaki, 1932 in Sufflamen
      fraenatum. New host and locality records are given of Lobatocreadium exiguum
      (Manter, 1963) in Pseudobalistes fuscus, which is also reported in the known
      hosts Abalistes filamentosus and Sufflamen fraenatum. New host and locality
      records are given of Opisthogonoporus amadai Yamaguti, 1937 in Branchiostegus
      wardi. A new host record is made for Holorchis plectorhynchi Durio et Manter,
      1968 in Diagramma pictum. New records in New Caledonian waters are of Bulbocirrus
      aulostomiYamaguti, 1965 in Aulostomus chinensis, Echeneidocoelium indicum Simha
      et Pershad, 1964 in Echeneis naucrates, Lepidapedoides kalikali Yamaguti, 1970 in
      Pristipomoides auricilla, Neomultitestis aspidogastriformis Bray et Cribb, 2003
      in Platax teira, Opechona bacillaris (Molin, 1859) in Rastrelliger kanagurta,
      Prodistomum keyam Bray et Cribb, 1996 in Monodactylus argenteus and
      Pseudopisthogonoporus vitellosus (Pritchard, 1963) in Naso brevirostris and N.
      annulatus. New metrical data are presented for Holorchis castex Bray et Justine,
      2007 in Diagramma pictum, Hypocreadium patellareYamaguti, 1938 in Sufflamen
      fraenatum, Intusatrium robustum Durio et Manter, 1968 in Bodianus loxozonus and
      B. perditio and Lepidapedoides angustus Bray, Cribb et Barker, 1996 in
      Epinephelus chlorostigma, E. fasciatus, E. maculatus and E. retouti. Literature
      records are included and the fauna in general discussed.

PMID- 22875675
TI  - Radix spp.: Identification of trematode intermediate hosts in the Czech Republic.
AB  - Lymnaeid snails of the genus Radix serve as intermediate hosts of some
      schistosomes and fasciolids. In Europe, delineation of species within the genus
      Radix is unresolved and, therefore, spectrum of snail hosts susceptible to
      trematode infections is under discussion. We used and compared three criteria for
      species delineation using snails collected at 43 localities. (a) Sequence
      analysis of ITS-2 rDNA disclosed that the collected snails belong to four species
      - R. auricularia (Linnaeus, 1758), R. peregra (Muller, 1774), R. lagotis
      (Schrank, 1803) and R. labiata (Rossmaessler, 1835) (criteria and names are based
      on the work of Bargues et al. 2001). Occurrence of R. peregra in the Czech
      Republic was confirmed by molecular data for the first time. (b) Characterization
      of reproductive system disclosed differences in location, size and shape of bursa
      copulatrix and its ductus. Unfortunately, some R. labiata specimens shared
      morphological features of reproductive organs with R. lagotis. (c) Statistical
      analysis of shell morphology proved that significant differences exist among
      particular species. One prediction model showed that correct classification of
      species may be achieved in 82-84% of cases. However, identification of individual
      snails in the field (without knowledge of respective snail population and use of
      statistical tools) still remains a complicated issue due to overlaps of shell
      characteristics. Concerning the role in trematode transmission, R. lagotis, R.
      labiata and R. peregra are susceptible to Trichobilharzia regenti. Also,
      successful experimental infections of R. lagotis and R. labiata by Fascioloides
      magna were accomplished.

PMID- 22875676
TI  - New genetic lineages, host associations and circulation pathways of Neorickettsia
      endosymbionts of digeneans.
AB  - Neorickettsia is a genus of intracellular bacteria endosymbiotic in digeneans
      that may also invade cells of vertebrates and are known to cause diseases of
      wildlife and humans. Herein, we report results of screening for Neorickettsia of
      an extensive collection of DNA extracts from adult and larval digeneans obtained
      from various vertebrates and mollusks in the United States. Seven isolates of
      Neorickettsia were detected by PCR and sequenced targeting a 527 bp long region
      of 16S rRNA. Sequence comparison and phylogenetic analysis demonstrated that four
      isolates matched published sequences of Neorickettsia risticii. Three other
      isolates, provisionally named "catfish agents 1 and 2" (obtained from Megalogonia
      ictaluri and Phyllodistomum lacustri, both parasitic in catfishes) and
      Neorickettsia sp. (obtained from cercariae of Diplostomum sp.), differed from
      previously known genotypes of Neorickettsia and are likely candidates for new
      species. All 7 isolates of Neorickettsia were obtained from digenean species and
      genera that were not previously reported as hosts of these bacteria. Members of
      four digenean families (Dicrocoeliidae, Heronimidae, Macroderoididae and
      Gorgoderidae) are reported as hosts of Neorickettsia for the first time. Our
      study reveals several new pathways of Neorickettsia circulation in nature. We
      have found for the first time a Neorickettsia from a digenean (dicrocoeliid
      Conspicuum icteridorum) with an entirely terrestrial life cycle. We found N.
      risticii in digeneans (Alloglossidium corti and Heronimus mollis) with entirely
      aquatic life cycles. Previously, this Neorickettsia species was known only from
      digeneans with aquatic/terrestrial life cycles. Our results suggest that our
      current knowledge of the diversity, host associations and circulation of
      neorickettsiae is far from satisfactory.

PMID- 22875677
TI  - Molecular identification of Diphyllobothrium latum and a brief review of
      diphyllobothriosis in China.
AB  - Two tapeworm specimens collected in northeast China in 2009 and 2011 were
      identified as Diphyllobothrium latum based on morphological criteria. Molecular
      methods were used to confirm their identity and analyze genetic variations
      compared with published data for this species. Species identity was confirmed by
      molecular characterization of the 18S rDNA partial sequence, complete sequences
      of internal transcribed spacers (ITSs) and 5.8S rDNA, and partial sequences of
      mitochondrial cytochrome c oxidase subunit 1 (cox1) and mitochondrial NADH
      dehydrogenase subunit 5 (nad5). PCR amplification and sequence analysis of 18S
      rDNA (1472 bp), ITS regions (1218 bp), cox1 (885 bp), and nad5 (1028 bp) revealed
      that these four sequences showed more than 99% identity to reference sequences
      for D. latum, confirming that this species is D. latum. To date, a total of 12
      diphyllobothriosis cases have been documented in China. This study represents the
      first molecular characterization of D. latum in China, providing molecular
      evidence of human diphyllobothriosis in China.

PMID- 22875678
TI  - SEM evidence for existence of an apical disc on the scolex of Clestobothrium
      crassiceps (Rudolphi, 1819): comparative results of various fixation techniques.
AB  - The scolex of the bothriocephalidean cestode Clestobothrium crassiceps was
      studied by means of scanning electron microscopy (SEM). The comparative results
      of various fixation procedures and techniques are presented. The scolex of C.
      crassiceps is oval to globular and exhibits two deep bothria which appear in the
      form of two lobes separated by a longitudinal groove. At the apex of the scolex,
      resembling a beret, an apical disc is present (oval, flattened and with a sinuous
      edge). Our results are compared with those previously reported in other species
      of Clestobothrium. This study represents the first report which highlights the
      presence of an apical disc in the scolex of C. crassiceps. It describes the
      effects of different procedures applied to our material during preparation and a
      comparative analysis results obtained using these various methods.

PMID- 22875679
TI  - Morphological and molecular characterisation of the entomoparasitic nematode
      Hammerschmidtiella diesingi (Nematoda, Oxyurida, Thelastomatidae).
AB  - A population of Hammerschmidtiella diesingi was detected in specimens of
      Periplaneta americana collected in Cordoba city (Argentina) was studied.
      Nematodes were characterized based on morphological, morphometric and genetic (D2
      D3 expansion segment) analyses. New data are provided, especially on particular
      morphological characters that were a matter of controversy in previous studies.
      H. diesingi is reported in Argentina for the first time.

PMID- 22875680
TI  - A new species of Aspiculuris Schulz, 1924 (Nematoda, Heteroxynematidae) from the
      gray-sided vole, Clethrionomys rufocanus (Rodentia, Cricetidae), from Tianjin,
      China.
AB  - Aspiculuris tianjinensis sp. nov. recovered from the intestine of Clethrionomys
      rufocanus from Tianjin, China is described and illustrated using light microscopy
      and scanning electron microscopy. The new species differs from congeners in the
      shape of the cervical alae, and the number and arrangement of caudal papillae.

PMID- 22875681
TI  - Morphological and molecular characterization of Raphidascaris (Ichthyascaris)
      lophii (Wu, 1949) (Nematoda, Anisakidae) from marine fishes from China, with a
      key to the species of the subgenus Ichthyascaris.
AB  - The little known ascaridoid nematode Raphidascaris (Ichthyascaris) lophii (Wu,
      1949) is redescribed and illustrated based on newly collected specimens from the
      five different marine fishes: Lophius litulon (Jordan) (Lophiiformes: Lophiidae),
      Lophiomus setigerus (Vahl) (Lophiiformes: Lophiidae), Antennarius hispidus (Bloch
      et Schneider) (Lophiiformes: Antennaridae), Zeus faber Linnaeus (Zeiformes:
      Zeidae) and Ostichthys japonicus (Cuvier) (Beryciformes: Holocentridae) from the
      East and South China Sea. This species differs from all congeners in the subgenus
      Ichthyascaris by the length of the ventricular appendix (0.52-0.98 mm long), the
      number and arrangement of caudal papillae (26-32 pairs of precloacal, 3-4 pairs
      of paracloacal and 8-11 pairs of postcloacal) and the length of the spicules
      (0.49-0.88 mm long, representing 3.08-4.70% of body length). In addition,
      nematodes collected from these five different fishes have been characterized
      using molecular methods by sequencing and analysing the internal transcribed
      spacer (ITS) of ribosomal DNA. No variation in size and nucleotide polymorphisms
      is detected within the target sequence among all samples analysed. These data
      contribute to facilitate an accurate diagnosis of this poorly known nematode. An
      identification key to the species of the subgenus Ichthyascaris is also provided.

PMID- 22875682
TI  - A new species of Colobomatus (Copepoda, Phylichthyidae) parasitic on Mullus
      argentinae (Perciformes, Mullidae) from South American Atlantic coast.
AB  - A new species of Colobomatus Hesse, 1873 is described from pores of the cephalic
      sensory system and nostrils of Argentine goatfish, Mullus argentinae Hubbs et
      Marini, 1933 (Perciformes: Mullidae), living along the southwestern Atlantic
      coast. The fish were collected at different latitudes, stretching from the State
      of Rio de Janeiro in the north, through Santa Catarina, Rio Grande do Sul
      (Brazil) to of Mar del Plata (Argentina) in the south. The prevalence of the
      infection ranged from 42% through 84%. The new species look alike to two other
      species, parasites of mullids (C. steenstrupi and C. mulli) particularly in the
      body shape and the number, shape, and ornamentation of cephalic, thoracic, and
      genital processes. The new species, however, can be readily distinguished by
      having the central cephalic process shorter than lateral ones, the later being
      bilobed at tip forked, and a relatively larger abdomen. Furthermore, C.
      steenstrupi possesses relatively wider trunk processes with rounded tips, a short
      abdominal dorsal process, and attains a larger size (up to 3.6 mm). C. mulli also
      differs by having all body processes with forked tips, and relatively shorter
      sixth thoracic somite and abdominal segments 1-3. This is the third record of a
      species of Colobomatus in South American Atlantic waters.

PMID- 22875683
TI  - Ornithodoros quilinensis sp. nov. (Acari, Argasidae), a new tick species from the
      Chacoan region in Argentina.
AB  - Ornithodoros quilinensis sp. nov. (Acari: Argasidae) is described from larvae
      collected on the small rodents Graomys centralis (Cricetidae: Sigmodontinae) in
      Argentina. The diagnostic characters for this new species are a combination of
      small size (520-540 MUm), a dorsal plate oval in shape with a length of
      approximately 200 MUm, 14 pairs of dorsal setae, hypostome short and narrower at
      the base (length from Ph(1) to apex 133 MUm (120-141)) with dental formula 2/2
      and apex blunt, and the capsule of the Haller's organ irregular in shape and
      without reticulations. The analysis of the 16S rDNA sequences available for the
      genus Ornithodoros indicate that, phylogenetically, O. quilinensis represents an
      independent lineage only related to a Bolivian tick species of the genus
      Ornithodoros yet not formally described.

PMID- 22875684
TI  - Accomplishing structural change: identifying intermediate indicators of success.
AB  - Coalitions are routinely employed across the United States as a method of
      mobilizing communities to improve local conditions that impact on citizens' well
      being. Success in achieving specific objectives for environmental or structural
      community change may not quickly translate into improved population outcomes in
      the community, posing a dilemma for coalitions that pursue changes that focus on
      altering community conditions. Considerable effort by communities to plan for and
      pursue structural change objectives, without evidence of logical and appropriate
      intermediate markers of success could lead to wasted effort. Yet, the current
      literature provides little guidance on how coalitions might select intermediate
      indicators of achievement to judge their progress and the utility of their
      effort. The current paper explores the strengths and weaknesses of various
      indicators of intermediate success in creating structural changes among a sample
      of 13 coalitions organized to prevent exposure to HIV among high-risk adolescents
      in their local communities.

PMID- 22875685
TI  - Advances in bridging research and practice: introduction to the second special
      issue on the interactive system framework for dissemination and implementation.
AB  - The need for new ways to bridge the gap between research and practice is clear;
      the use of evidence-based prevention programs and implementation with fidelity in
      practice are strikingly limited. The Interactive Systems Framework for
      Dissemination and Implementation (ISF) was created to help bridge research and
      practice by specifying the systems and processes required to support
      dissemination and implementation of evidence-based programs, processes,
      practices, and policies. The ISF identifies three key systems necessary for this
      process which include the Synthesis and Translation System, the Support System,
      and the Delivery System. The ISF was featured in a special issue of the American
      Journal of Community Psychology in 2008. This special issue extends that work by
      including both researchers who have applied an ISF lens to aspects of their
      current work and researchers who have proactively applied the ISF in a process
      that goes across the various systems of the ISF, i.e., Synthesis and Translation,
      Support, and Delivery. Content areas include: children's mental health, teen
      pregnancy prevention, HIV prevention, violence prevention, heart disease and
      stroke prevention, breast cancer prevention, and substance abuse prevention. In
      this introductory article, we provide a brief description of the history of the
      ISF and a summary of the articles in the special issue.

PMID- 22875686
TI  - The impact of participatory research on urban teens: an experimental evaluation.
AB  - Although there is much practice of community-based participatory research in
      economically-developing countries and increasingly in North America, there has
      been little systematic assessment of empowerment effects. Youth-led participatory
      research holds particular promise for fostering positive development and civic
      participation among economically disadvantaged urban youth. The present
      investigation uses a clustered-randomized, within-school experimental design to
      test the effects of youth-led participatory research on the psychological
      empowerment of 401 students attending urban public schools. We find that
      attending a participatory research elective class during the school day was
      associated with increases in sociopolitical skills, motivation to influence their
      schools and communities, and participatory behavior. We found no significant
      effects for perceived control at school. The implications for participatory
      research and related youth development interventions are discussed.

PMID- 22875687
TI  - Backbone resonance assignments of the micro-RNA precursor binding region of human
      TRBP.
AB  - TAR-RNA binding protein (TRBP) is a multidomain human protein involved in micro
      RNA (miRNA) biogenesis. TRBP is a component of both the Dicer complex, which
      processes precursor miRNAs, and the RNA-induced silencing complex-loading
      complex. In addition, TRBP is implicated in the human immunodeficiency virus
      replication cycle and interferon-protein kinase R activity. TRBP contains 3
      double-stranded RNA binding domains the first two of which have been shown to
      interact with miRNA precursors. Here we present the backbone resonance
      assignments and secondary structure of residues 19-228 of human TRBP2. 

PMID- 22875688
TI  - Management of knee deformities in children with arthrogryposis.
AB  - Arthrogryposis includes heterogeneous disorders, characterized by congenital
      contractures of multiple joints. Knee involvement is very common (38-90 % of
      patients with amyoplasia) ranging from soft-tissue contractures (in flexion or
      hyperextension) to subluxation and dislocation. Flexion contractures are more
      common and disabling and show significant resistance to treatment and rate of
      recurrence. Surgical procedures vary with severity of contracture and patient age
      and include soft-tissue release, femoral shortening-extension osteotomy, gradual
      correction with Ilizarov, and femoral anterior epiphysiodesis. The presence of
      pterygium greatly complicates treatment, given the high rate of complications
      reported. Hyperextension deformities (recurvatum, anterior subluxation, and
      dislocation) have better prognosis for walking ability. Surgical options include
      percutaneous (or mini-open) quadriceps tenotomy, open quadricepsplasty, and
      femoral shortening osteotomy with limited arthrotomy. Knee dislocations usually
      require surgery and should be reduced early.

PMID- 22875689
TI  - [Age, sex and diagnostic distribution of patients in  ophthalmological medical
      practice in Germany].
AB  - OBJECTIVE: The ophthalmological patient care in Germany has changed over the past
      decades due to demographic and diagnostic facility change and the shift from
      inpatient to outpatient care. METHOD: In the fourth quarter of 2010 a survey was
      conducted including almost 10 % of the patients of 96 ophthalmologists. The
      results for age, sex, main and secondary diagnosis and the main reason for the
      examination were examined and compared with those of surveys from 1966 and 1997.
      RESULTS: 15125 patients (median per doctor: 149, range: 45-376) were included in
      the survey. 58 % were women. The proportion of women was elevated in all decades
      compared to men, apart from the first age decade. The proportion of older
      patients (70 +) increased (1997: 25.3 %; 2010: 40.8 %) although the age
      distribution in Germany appears to be rather constant (1997: 11.9 %; 2010: 15.3
      %). The proportion of examinations due to glaucoma, diabetes and vitreoretinal
      diseases increased by almost 60 % compared to 1997. CONCLUSION: Compared to the
      results of 1997, we observed a marked change from simple to differentiated cases
      in ophthalmological medical practice in Germany. The early diagnosis and therapy
      have to be guaranteed in the future taking into account the limited resources.

PMID- 22875690
TI  - [Polymicrobial brain abscess in hereditary haemorrhagic telangiectasia  (Osler's
      disease)].
AB  - HISTORY AND ADMISSION FINDINGS: A 38-year-old woman who suffered from migraine
      was admitted because of severe, worsening headache for 24 hours (dissimilar to
      the previous migraine attacks), with impaired vision and weakness of the right
      arm. Mild hemiparesis and expressive aphasia indicated an intracranial tumor.
      INVESTIGATIONS: Cranial computed tomography revealed a focal lesion with a
      diameter of 2.5 cm in the left frontoparietal lobe, with signs of intracranial
      hypertension, indicating cerebral metastasis or an abscess. Magnetic resonance
      imaging confirmed the diagnosis of a brain abscess. TREATMENT AND COURSE: An
      urgent craniotomy was performed and the abscess was evacuated. An empirical
      antibiotic combination with chloramphenicole and metronidazole (switched to
      cefotaxime because of thrombocytopenia) was initiated. Cultivation of pus
      revealed Streptococcus constellatus, Aggregatibacter aphrophilus and
      Fusobacterium spp. Within the first two weeks of treatment progession of the
      abscess was noted, therefore a second craniotomy with debridement was performed.
      An elective CT-angio scan revealed several arteriovenous malformations in the
      caudal segments of both lungs which were embolized without complications. Only
      retrospectively, cutaneous teleangiectasias were recognized. At present, the
      patient and her direct relatives are submitted to genetical screening for Osler's
      disease. CONCLUSION: In patients with brain abscesses of unknown origin and with
      a history of repeated epistaxis and/or gastrointestinal bleeding, Osler's disease
      (hereditary hemorrhagic telangiectasia) should be considered and pulmonary
      arteriovenous malformations excluded. Physicians should search for cutaneous or
      mucous teleangiectasias. Family screening and long-term follow-up according to
      international guidelines is recommended.

PMID- 22875691
TI  - [75-year-old woman with symptoms of the eye].

PMID- 22875692
TI  - [Radionuclide therapy for the treatment of skeletal metastases of urological
      malignancies: a forgotten therapy?].
AB  - Many patients suffering from urological or non-urological malignancies develop
      bone metastases. One symptom often found is severe skeletal pain which
      siginificantly lowers the quality of life. Further symptoms are pathological
      fractures, spinal cord compression and hypercalcemia. The systemic
      radiopharmaceutical therapy represents an important systemic treatment option, in
      addition to chemotherapy, hormone therapy, external beam radiation,
      bisphosphonates and analgesics. The radionuclide therapy is rarely used and often
      used in a later phase of disease, mainly known for the bone pain palliation. This
      review article should help remind physicians to use this interesting therapy. It
      focuses on the common radionuclides Strontium-89-chloride, Samarium-153-EDTMP
      (ethylene-diamine-tetra-methylene-phosphonate) and Rhenium-186-HEDP
      (hydroxyethylidene-diphosphonate), their physical characteristics and
      differences, contraindications of the therapy like spinal cord compression and
      side effects. Additionally, potential tumoricidal activity and improvement of
      survival are discussed when using the radionuclides repetitively or in
      combination. The European and German guidelines are included. Furthermore, the
      combination of radionuclides and bisphosphonates or chemotherapy are briefly
      discussed, based on available clinical studies. Additionally, alpharadin (radium
      223 chloride) is discussed, an experimental radiopharmaceutical under clinical
      evaluation, which emits alpha-radiation. In phase III clinical trials, it was
      shown to significantly increase the median overall survival in patients with bone
      metastases from advanced prostate cancer.

PMID- 22875693
TI  - [Early asymptomatic GIST of the stomach].

PMID- 22875694
TI  - [Cardiac two-pore-domain potassium channels (K2P):  Physiology, pharmacology, and
      therapeutic potential].
AB  - Uncontrolled electrical activity caused by ion channel dysfunction produces
      arrhythmia in the heart. Despite recent advances in pharmaceutical research and
      development, effective and safe pharmacological management of cardiac arrhythmia
      still remains an unmet medical need. The emerging family of two-pore-domain
      potassium (K2P) channels stabilizes the resting membrane potential and
      facilitates action potential repolarization. In the heart, genetic inactivation
      or inhibition of two-pore-domain K + (K2P) currents by class III antiarrhythmic
      drugs results in action potential prolongation. In particular, human K2P3.1
      channels are selectively expressed in the atria and represent targets for the
      pharmacological management of atrial fibrillation. Furthermore, stretch-sensitive
      K2P2.1 channels are implicated in mechanoelectrical feedback and
      arrhythmogenesis. The current knowledge on function, regulation, and cardiac
      significance of K2P channels is summarized in this work, and potential
      therapeutic implications are highlighted.

PMID- 22875695
TI  - [New data for transcatheter aortic valve implantation (TAVI)].

PMID- 22875696
TI  - [Diabetic alert dogs: A good nose for hypoglycemia].

PMID- 22875697
TI  - Graphene oxide used as a carrier for adriamycin can reverse drug resistance in
      breast cancer cells.
AB  - This study evaluates the reversal effects of graphene oxide (GO) used as a
      carrier for adriamycin (ADR) in cancer drug resistance, and provides a
      preliminary investigation into the reversal mechanism. ADR was loaded onto the GO
      surface (ADR-GO) by physical mixing and drug loading content was found to be
      high, up to 93.6%. In vitro releases of ADR from ADR-GO were studied using a
      dialysis method, and they exhibited a significant pH-sensitive property. Cell
      experiments showed that GO significantly enhanced the accumulation of ADR in MCF
      7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher
      cytotoxicity than free ADR, suggesting that ADR-GO could effectively reverse ADR
      resistance of MCF-7/ADR, with the reversal index reaching 8.35. Microscopy
      studies found that GO could effectively carry drug molecules into cells in both
      endocytosis-dependent and independent manners. In conclusion, use of GO as a
      carrier for chemotherapeutic agents is favorable for the treatment of drug
      resistant cancers.

PMID- 22875698
TI  - Low-dose imatinib in the treatment of severe systemic sclerosis: a case series of
      six Chinese patients and literature review.
AB  - Systemic sclerosis (SSc) is a progressive fibrotic disorder with no legitimate
      effective treatment. Several clinical trials had investigated imatinib mesylate
      with a target dose of 400~600 mg/day on SSc, and the efficacy is controversial
      with a generally poor tolerability. We herein reported six female Chinese
      patients with SSc administered with low-dose imatinib (200 mg/day) for a median
      of 23 months (10~30 months). Patients displayed a decreased modified Rodman skin
      scores (mRSS) by a mean of 6.29 points after 6 months of treatment. Three
      patients who completed 2 years of treatment achieved a reduction of mRSS by 8,
      18, and 30.5 points, respectively. Pulmonary function was improved or stabilized
      in two patients with interstitial lung disease. Severe gastrointestinal
      involvement in one patient was attenuated in terms of discontinuation of total
      parenteral nutrition and restoration of the serum albumin level. Imatinib was
      well-tolerated in general, although there were two severe adverse events: a bone
      fracture and a cerebral hemorrhage in two individuals. Both the adverse events
      were probably not directly related to imatinib and were recovered uneventfully.
      Our limited data, along with the review of the literature, suggested that low
      dose imatinib might be effective and better tolerated in severe SSc that deserves
      further study.

PMID- 22875699
TI  - Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto
      disease-including some interesting cases.
AB  - Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited disease characterized by
      tender regional lymphadenopathy with fever. KFD remains a poorly defined disease,
      and no clear diagnostic criteria are available. Here, we assess the clinical,
      laboratory, and histopathologic findings of KFD cases and report two unusual
      cases. Forty KFD patients that underwent lymph node (LN) biopsy and diagnosed by
      immunohistochemical staining, from January 2003 to November 2010, were enrolled
      in this retrospective study. The patients had a mean age of 29.3 years, and 29
      (72.5 %) were women. Affected LNs were mainly located unilaterally in the
      cervical area. Mean LN size was 15.3 mm. Twenty-eight (70 %) patients had LN
      tenderness, and 25 (62.5 %) patients had fever. Leukopenia was observed in 18 of
      35 evaluable patients. C-reactive protein and erythrocyte sedimentation rate were
      elevated in most patients. Anti-nuclear antibody was positive in four of 19
      evaluable patients, but all had been diagnosed with concurrent systemic lupus
      erythematosus. Histologically, the 40 cases were classified into three types,
      that is, as proliferative (37.5 %), necrotizing (55.0 %), or xanthomatous (7.5
      %). Interesting cases: Case 1 was a 35-year-old female with KFD and uveitis,
      retinal vasculitis, and superior sagittal sinus thrombosis. Case 2 was a 47-year
      old male with KFD and bone marrow involvement and presented with severe
      bicytopenia. Although KFD is an uncommon self-limited benign disorder, it must be
      included in the differential diagnosis of lymphadenopathy with fever and
      cytopenia. It is important that the clinical features of KFD be understood to
      reach a correct diagnosis.

PMID- 22875700
TI  - The effect of neutralizing antibodies on the sustainable efficacy of biologic
      therapies: what's in it for African and Middle Eastern rheumatologists.
AB  - Over the last decade, biologic therapeutic proteins have advanced the treatment
      of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as
      infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol,
      the receptor construct etanercept, and abatacept, an anticluster of
      differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and
      ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab
      pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key
      regulator of inflammation. Left untreated, progression of rheumatic diseases due
      to inflammation can lead to irreversible joint damage and serious disability. One
      limitation for the use of therapeutic antibodies is immunogenicity, the induction
      of antibodies by the adaptive immune system in response to foreign substances.
      The development of antidrug antibodies (ADAs) has a varying impact on the
      clinical efficacy of biologic agents for the treatment of RA and AS, depending on
      whether the ADAs are neutralizing or non-neutralizing. Studies have indicated
      that neutralizing ADAs are associated with a reduced efficacy, decreased drug
      survival, increased instances of dose escalation, and adverse events. Comparison
      studies of anti-TNF biologics have demonstrated that each drug has a different
      sustained efficacy profile depending on immunogenicity. The purpose of this
      review is to provide rheumatologists with information regarding the effect of
      neutralizing antibodies on the sustainable efficacy of anti-TNF biologic
      therapies. This information will be of value to practicing rheumatologists in
      Africa and the Middle East who should take into account the potential for changes
      in the efficacy and safety of biologic therapies and closely monitor patients
      under their care.

PMID- 22875701
TI  - Drug compliance in patients with systemic scleroderma.
AB  - Although drug compliance is a crucial component of treatment effectiveness in
      chronic diseases, it has never been evaluated in patients with systemic
      scleroderma. Therefore, the aim of this descriptive study was to determine the
      drug compliance rate in systemic scleroderma patients and to identify risk
      factors for noncompliance in these patients. A cross-sectional observational
      study was conducted. All patients with systemic scleroderma (n = 41) who visited
      a rheumatic center and signed an informed consent form were included. Data were
      obtained during structured interviews with patients and from medical records. The
      Compliance Questionnaire Rheumatology (CQR) was used to determine patient
      compliance. The relationships between compliance rate and demographic and
      clinical characteristics were examined. The mean CQR score was 75 %. Based on a
      dichotomous rating, only 42 % of the patients achieved a satisfactory compliance
      rate (>=80 %). No relationships between various demographic and clinical
      characteristics and CQR score expressed as continuous or dichotomous variables
      were found. This study represents the first evaluation of drug compliance in
      patients with systemic scleroderma. Many noncompliant patients were identified,
      but no common risk factors for noncompliance were discovered. The reasons for
      noncompliance seem to depend on the personal features of the patients.

PMID- 22875702
TI  - Fibromyalgia and hysterectomy: the impact on health status and health care costs.
AB  - Women account for over 80 % of the fibromyalgia syndrome (FMS) population. Some
      researchers have noted that a large percentage of women with FMS have had
      hysterectomies. The purpose of this study was to examine the relationship between
      FMS and hysterectomies, and to examine the impact of having a hysterectomy on
      health status and health care costs. A sample of 573 American women, who were
      members of a health maintenance organization with a confirmed diagnosis of FMS,
      reported whether they had a hysterectomy. Participants completed the Quality of
      Well-Being Scale and their annual health care costs were calculated based on
      their medical records. Almost half of the sample (48.3 %) reported having had a
      hysterectomy, with 90.7 % reporting having had the surgery before their FMS
      diagnosis. Those who had a hysterectomy had significantly lower general health
      status and incurred higher health care costs than the women with FMS who did not
      have a hysterectomy. The percentage of women with FMS who had a hysterectomy was
      considerably higher than that found in the general population. In this study,
      having a hysterectomy and a diagnosis of FMS was related to poorer health status
      and higher health care costs.

PMID- 22875703
TI  - A vaccine directed to B cells and produced by cell-free protein synthesis
      generates potent antilymphoma immunity.
AB  - Clinical studies of idiotype (Id) vaccination in patients with lymphoma have
      established a correlation between the induced anti-Id antibody responses and
      favorable clinical outcomes. To streamline the production of an Id vaccine, we
      engineered a small diabody (Db) molecule containing both a B-cell-targeting
      moiety (anti-CD19) and a lymphoma Id. This molecule (alphaCD19-Id) was designed
      to penetrate lymph nodes and bind to noncognate B cells to form an antigen
      presentation array. Indeed, the alphaCD19-Id molecule accumulated on B cells in
      vivo after s.c. administration. These noncognate B cells, decorated with the
      diabody, could then stimulate the more rare Id-specific B cells. Peptide epitopes
      present in the diabody linker augmented the response by activating CD4(+) helper
      T cells. Consequently, the alphaCD19-Id molecule induced a robust Id-specific
      antibody response and protected animals from tumor challenge. Such diabodies are
      produced in a cell-free protein expression system within hours of amplification
      of the specific Ig genes from the B-cell tumor. This customized product can now
      be available to vaccinate patients before they receive other, potentially
      immunosuppressive, therapies.

PMID- 22875704
TI  - Complement factor H genotypes impact risk of age-related macular degeneration by
      interaction with oxidized phospholipids.
AB  - The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH)
      has been identified by genome-wide association studies as being significantly
      associated with age-related macular degeneration (AMD). However, the precise
      mechanism by which this CFH variant impacts the risk of AMD remains largely
      unknown. Oxidative stress plays an important role in many aging diseases,
      including cardiovascular disease and AMD. A large amount of oxidized
      phospholipids (oxPLs) are generated in the eye because of sunlight exposure and
      high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages
      and strongly activate downstream inflammatory cascades. We hypothesize that CFH
      may impact the risk of AMD by modulating oxidative stress. Here we demonstrate
      that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170
      genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory
      effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In
      addition, plasma from non-AMD subjects with the protective genotype has a lower
      level of systemic oxidative stress measured by oxPLs per apolipoprotein B
      (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes
      involved in macrophage infiltration, inflammation, and neovascularization in the
      eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal
      injection of oxPLs induces choroidal neovascularization in mice. In addition, we
      show that the CFH risk allele confers higher complement activation and cell lysis
      activity. Together, these findings suggest that CFH influences AMD risk by
      modulating oxidative stress, inflammation, and abnormal angiogenesis.

PMID- 22875705
TI  - Location of natural oil seep and chemical fingerprinting suggest alternative
      explanation for deep sea coral observations.

PMID- 22875706
TI  - CT322, a VEGFR-2 antagonist, demonstrates anti-glioma efficacy in orthotopic
      brain tumor model as a single agent or in combination with temozolomide and
      radiation therapy.
AB  - Glioblastomas are among the most aggressive human cancers, and prognosis remains
      poor despite presently available therapies. Angiogenesis is a hallmark of
      glioblastoma, and the resultant vascularity is associated with poor prognosis.
      The proteins that mediate angiogenesis, including vascular endothelial growth
      factor (VEGF) signaling proteins, have emerged as attractive targets for
      therapeutic development. Since VEGF receptor-2 (VEGFR-2) is thought to be the
      primary receptor mediating angiogenesis, direct inhibition of this receptor may
      produce an ideal therapeutic effect. In this context, we tested the therapeutic
      effect of CT322, a selective inhibitor of VEGFR-2. Using an intracranial murine
      xenograft model (U87-EGFRvIII-luciferase), we demonstrate that CT322 inhibited
      glioblastoma growth in vivo and prolonged survival. Of note, the anti-neoplastic
      effect of CT322 is augmented by the incorporation of temozolomide or temozolomide
      with radiation therapy. Immunohistochemical analysis of CT322 treated tumors
      revealed decreased CD31 staining, suggesting that the tumoricidal effect is
      mediated by inhibition of angiogenesis. These pre-clinical results provide the
      foundation to further understand long term response and tumor escape mechanisms
      to anti-angiogenic treatments on EGFR over-expressing glioblastomas.

PMID- 22875707
TI  - Conditional survival of high-grade glioma in Los Angeles County during the year
      1990-2000.
AB  - Survival probabilities for high-grade glioma are estimated at the time of
      diagnosis and provide limited information following treatment. This study
      determined dynamic indices to predict post-diagnosis survival for high-grade
      glioma patients. Survival information for 2,743 patients with high-grade glioma,
      diagnosed in Los Angeles County during the years 1990-2000, were used to estimate
      conditional survival probabilities with 95 % confidence intervals, for patients
      still alive at 1, 2, 3, 4, or 5 years after diagnosis. The conditional
      probabilities of surviving one additional year increase as the post-diagnosis
      survival time increases (from 43 +/- 2 % conditional on surviving 1 year after
      diagnosis to 91 +/- 2 % conditional on surviving 5 years after diagnosis).
      Patients diagnosed with WHO grade III gliomas have higher conditional survival
      probabilities than those diagnosed WHO grade IV gliomas. However, as the years
      after diagnosis increase, the differences in the conditional probabilities
      between the two groups are attenuated. At the time of diagnosis, age and tumor
      histology (WHO grade), tumor site, primary treatment, time of treatment start
      after diagnosis, as well as whether the patient was treated at a teaching
      hospital were significantly associated with overall survival. By 4 years post
      diagnosis however, with the exception of age, variables associated with survival
      at baseline were no longer significantly associated with survival. Conditional
      survival probabilities provide clinically relevant information for understanding
      the prognosis for patients with high-grade gliomas.

PMID- 22875708
TI  - Presentation, management, and outcome of elderly patients with newly-diagnosed
      anaplastic astrocytoma.
AB  - Few studies have assessed the presentation, management, and outcome of anaplastic
      astrocytoma (AA) in elderly patients in the temozolomide era. We retrospectively
      reviewed 42 consecutive patients aged >65 years with newly-diagnosed AA who
      underwent surgical resection or biopsy between 2003 and 2008. Median age and KPS
      score were 73 years (range, 66-88) and 80 (range, 50-90), respectively. Thirty
      two patients (76 %) presented with focal deficits. Twenty patients (48 %)
      experienced seizures before surgery. Tumor enhanced diffusely in 24 patients (57
      %) and sparsely in 18 patients (43 %). Biopsy (79 %) was more common than
      resection. Post-operatively, new persistent neurological deficits and hemorrhage
      were seen in two (4.8 %) and three (7.1 %) patients, respectively. Complete
      follow-up data regarding adjuvant treatment was available in 31 patients. Sixteen
      patients (52 %) received temozolomide and radiation therapy (RT), while nine
      patients (29 %) received RT alone. Chemotherapy-related grade 3/4 hematologic
      complication rate was 17.6 %. Median overall survival (OS) was 6.5 months (12
      months with resection; 3.5 months with biopsy). Resection (P = 0.007, risk ratio
      = 0.21) and sparse enhancement (P = 0.007, risk ratio = 0.13) were associated
      with longer OS in multivariate analysis. Similarly, chemoradiation was associated
      with longer survival compared to RT alone (OS: P = 0.01, progression-free
      survival (PFS): P = 0.02) after adjusting for age, KPS, enhancement, and surgery.
      Resection was associated with longer survival among elderly patients with AA,
      although this could reflect selection bias. Similarly, adding chemotherapy to RT
      was associated with prolonged survival but carried important complication risks.
      In appropriately selected AA patients, aggressive treatments with radical
      resection and chemoradiation may be appropriate even in this age group.

PMID- 22875709
TI  - Phase I study of arsenic trioxide and temozolomide in combination with radiation
      therapy in patients with malignant gliomas.
AB  - To evaluate the toxicity and maximum tolerated dose (MTD) of arsenic trioxide
      (ATO) in combination with temozolomide (TMZ) and radiation therapy (RT) in
      malignant gliomas. A 3 + 3 dose escalation study was performed in patients with
      newly diagnosed glioblastoma, anaplastic astrocytoma (AA), and anaplastic
      oligoastrocytoma (AOA). All patients received RT 59-61 Gy in 28-33 fractions, TMZ
      for 42 days, and ATO 1-2 h prior to RT for 5 days during the first week, then
      twice weekly until completing RT. Dose levels (DL) were: (1) TMZ 60 mg/m(2)/ATO
      0.2 mg/kg; (2) TMZ 75 mg/m(2)/ATO 0.2 mg/kg; (3) TMZ 75 mg/m(2)/ATO 0.25 mg/kg.
      Dose-limiting toxicity (DLT) was defined as grade 3 non-hematologic toxicity or
      grade 4 toxicity of any type from enrollment until 3 weeks after finishing RT. 17
      patients (13 glioblastoma, 4 AA/AOA) were accrued. Median age was 52 (range 25
      80). Median KPS was 90 %. DLT's occurred at DL 2 (grade 4 transaminase elevation)
      and DL 3 (grade 4 neutropenia and grade 3 QTc prolongation). The MTD of TMZ 75
      mg/m(2)/ATO 0.2 mg/kg was safe and well tolerated. A phase II study evaluating
      the efficacy of this combination is underway.

PMID- 22875711
TI  - The challenges of eating a healthy and sustainable diet.

PMID- 22875710
TI  - Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand
      KM-233.
AB  - Glioblastoma multiforme (GBM) is the most common and devastating form of primary
      central nervous system malignancy. The prognosis for patients diagnosed with GBM
      is poor, having a median survival rate of 12-15 months. Despite modern advances
      in the development of antineoplastic agents, the efficacy of newer anti-cancer
      agents in the treatment of GBM is yet to be determined. Thus, there remains a
      significant unmet need for new therapeutic strategies against GBM. A promising
      chemotherapeutic intervention has emerged from studies of cannabinoid receptor
      agonists wherein tetrahydrocannabinol has been the most extensively studied. The
      novel cannabinoid ligand KM-233 was developed as a lead platform for future
      optimization of biopharmaceutical properties of classical based cannabinoid
      ligands. Treatment of U87MG human GBM cells with KM-233 caused a time dependent
      change in the phosphorylation profiles of MEK, ERK1/2, Akt, BAD, STAT3, and
      p70S6K. Almost complete mitochondrial depolarization was observed 6 h post
      treatment followed by a rapid increase in cleaved caspase 3 and significant
      cytoskeletal contractions. Treatment with KM-233 also resulted in a
      redistribution of the Golgi-endoplasmic reticulum structures. Dose escalation
      studies in the orthotopic model using U87MG cells revealed an 80 % reduction in
      tumor size after 12 mg/kg daily dosing for 20 days. The evaluation of KM-233
      against primary tumor tissue in the side flank model revealed a significant
      decrease in the rate of tumor growth. These findings indicate that structural
      refinement of KM-233 to improve its biopharmaceutical properties may lead to a
      novel and efficacious treatment for GBM.

PMID- 22875712
TI  - Weight loss produced by gastric bypass surgery: more gut feelings hit the brain.

PMID- 22875713
TI  - Prospective cohort studies of vitamin B-6 intake and colorectal cancer incidence:
      modification by time?
AB  - BACKGROUND: The relation between vitamin B-6 intake and colorectal cancer risk
      remains uncertain. OBJECTIVE: We prospectively evaluated whether a higher vitamin
      B-6 intake in the remote past is more strongly associated with a lower risk of
      colorectal cancer than is an intake in the recent past in the Nurses' Health
      Study and the Health Professionals Follow-Up Study. DESIGN: We assessed vitamin B
      6 intake every 4 y by using validated food-frequency questionnaires and followed
      86,440 women and 44,410 men for <=28 y. Cox proportional hazards regression was
      used to estimate multivariable RRs and 95% CIs. RESULTS: The total vitamin B-6
      intake was significantly associated with an ~20-30% lower risk of colorectal
      cancer in age-adjusted results, but this association became attenuated and
      nonsignificant after additional adjustment for nondietary and dietary factors.
      When the highest to lowest quintiles of cumulative total vitamin B-6 intake were
      compared, RRs (95% CIs) for colorectal cancer were 0.99 (0.80, 1.24; P-trend =
      0.55) for women and 0.95 (0.73, 1.23; P-trend = 0.75) for men. For the same
      comparison, RRs were 0.92 (0.73, 1.16) for total vitamin B-6 intake 0-4 y before
      diagnosis, 0.99 (0.78, 1.26) for intake 4-8 y before diagnosis, 0.92 (0.71, 1.21)
      for intake 8-12 y before diagnosis, and 0.93 (0.69, 1.26) for intake 12-16 y
      before diagnosis in women. Corresponding RRs for men were 0.86 (0.63, 1.17), 0.96
      (0.70, 1.32), 0.90 (0.63, 1.29), and 1.16 (0.75, 1.79). Results did not differ by
      cancer subsite, source of vitamin B-6 (food or supplement), alcohol consumption,
      or folate intake. CONCLUSION: Our data do not support a strong role of adulthood
      vitamin B-6 intake in colorectal carcinogenesis in these US health professionals.

PMID- 22875715
TI  - Men and women with bisexual identities show bisexual patterns of sexual
      attraction to male and female "swimsuit models".
AB  - Do self-identified bisexual men and women actually show bisexual patterns of
      sexual attraction and interest? To answer this question, I studied bisexual men's
      and women's sexual attraction to photographed male and female "swimsuit models"
      that varied in attractiveness. Participants (663 college students and gay pride
      attendees, including 14 self-identified bisexual men and 17 self-identified
      bisexual women) rated their degree of sexual attraction to 34 male and 34 female
      swimsuit models. Participants' viewing times to models were unobtrusively
      assessed. Results showed that bisexual men and women showed bisexual patterns of
      attraction and viewing times to photo models, which strongly distinguished them
      from same-sex heterosexual and homosexual participants. In contrast to other
      groups, which showed evidence of greater male than female category specificity,
      bisexual men and women did not differ in category specificity. Results suggest
      that there are subsets of men and women who display truly bisexual patterns of
      sexual attraction and interest.

PMID- 22875714
TI  - Mediastinal lymph nodes: ignore? sample? dissect? The role of mediastinal node
      dissection in the surgical management of primary lung cancer.
AB  - The role of mediastinal lymph node dissection (MLND) during the resection of non
      small-cell lung cancer is still unclear although most surgeons agree that a
      minimum of hilar and mediastinal nodes must be examined for appropriate
      pathological staging. Current surgical practices vary from visual inspection of
      the mediastinum with biopsy of only abnormal looking nodes to systematic
      mediastinal node sampling which is to the biopsy of lymph nodes from multiple
      levels whether they appear abnormal or not to MLND which involves the systematic
      removal of all lymph node bearing tissue from multiple sites unilaterally or
      bilaterally within the mediastinum. This review article looks at the evidence and
      arguments in favour of lymphadenectomy, including improved pathological staging,
      better locoregional control, and ultimately longer disease-free survival and
      those against which are longer operating time, increased operative morbidity, and
      lack of evidence for survival benefit.

PMID- 22875716
TI  - Actor-partner effects of demographic and relationship factors associated with HIV
      risk within gay male couples.
AB  - Recent research has investigated the association of relationship factors and
      dynamics with sexual behaviors and HIV risk among gay male couples. However, few
      studies with gay male couples have used the Actor-Partner Interdependence Model
      framework to examine whether factors influence an individual and his partner's
      sexual risk behaviors. None of these studies analyzed whether relationship
      factors had influenced the sexual risk behaviors of both partners within the
      couple. Our cross-sectional study used dyadic data from 142 gay male couples to
      assess actor-partner effects of relationship commitment, trust, and investment in
      one's sexual agreement for HIV risk. Multilevel modeling was used to examine
      which actor-partner effects of these factors were predictive of individuals and
      their partners having had UAI within and outside the relationship. Results
      indicated that participants' likelihood of having had UAI within and outside of
      the relationship significantly decreased with: (1) actor effects of value in and
      commitment to a sexual agreement, and quality of alternatives to the relationship
      and (2) partner effects of participant's age, dependability of trust, quality of
      alternatives to the relationship, and investment of relationship commitment. No
      significant actor-partner effects were detected for having had UAI within the
      relationship. Our findings suggest that future HIV prevention strategies should
      take into account how relationship factors influence an individual and his main
      partners' sexual risk behaviors and in turn, the couple's risk for HIV. However,
      more research is needed to examine how actor-partner effects of relationship
      factors influence a variety of sexual risk behaviors within gay male couples. 

PMID- 22875717
TI  - Heterosexual daters' sexual initiation behaviors: use of the theory of planned
      behavior.
AB  - The current study investigated sexual initiations within the framework of the
      Theory of Planned Behavior (TPB) (Ajzen, 1991; Ajzen & Madden, 1986). Male and
      female daters in heterosexual dating relationships completed an online survey
      that assessed their sexual relationship with their partner and the TPB components
      (perceptions of social norms, attitudes, perceived behavioral control, and
      intentions). The TPB was supported for both men and women in that, as predicted,
      the more an individual perceived that important others would approve of them
      initiating sexual activities with their partner, the more positive their
      evaluations were of the outcomes of initiating, and the more confident they were
      in their ability to initiate, the stronger were their initiation intentions. In
      turn, stronger sexual initiation intentions were associated with more frequent
      initiation behaviors. Compared to women, men initiated more frequently, had
      stronger sexual initiation intentions, and perceived more positive social norms
      regarding initiation; men and women did not differ in their attitudes toward
      sexual initiation or in their perceived behavioral control. Both men and women
      who reported initiating more frequently and perceived their partner as initiating
      more frequently reported greater sexual satisfaction. These results are discussed
      in terms of the utility of the TPB for understanding sexual initiations and the
      role of the traditional sexual script in initiation-related cognitions and
      behavior.

PMID- 22875718
TI  - Predictors of sexual assertiveness: the role of sexual desire, arousal,
      attitudes, and partner abuse.
AB  - This study was conducted to test interpersonal, attitudinal, and sexual
      predictors of sexual assertiveness in a Spanish sample of 1,619 men and 1,755
      women aged 18-87 years. Participants completed measures of sexual assertiveness,
      solitary and dyadic sexual desire, sexual arousal, erectile function, sexual
      attitudes, and frequency of partner abuse. In men, higher sexual assertiveness
      was predicted by less non-physical abuse, more positive attitudes toward sexual
      fantasies and erotophilia, higher dyadic desire, and higher sexual arousal. In
      women, higher sexual assertiveness was predicted by less non-physical abuse, less
      solitary sexual desire and higher dyadic sexual desire, arousal, erotophilia, and
      positive attitudes towards sexual fantasies. Results were discussed in the light
      of prevention and educational programs that include training in sexual
      assertiveness skills. 

PMID- 22875719
TI  - Long-term prognostic value of exercise technetium-99m tetrofosmin myocardial
      perfusion single-photon emission computed tomography.
AB  - BACKGROUND: Exercise (99m)Tc-tetrofosmin single-photon emission computed
      tomography (SPECT) is a useful tool for short- and medium-term risk
      stratifications. Currently, the long-term prognostic application of this
      technique has not been evaluated. METHODS AND RESULTS: Exercise (99m)Tc
      tetrofosmin was performed in 655 consecutive patients. Ten patients who underwent
      revascularization <60 days after nuclear testing were excluded from the analysis.
      The present data are based on 638 patients with complete follow-up. An abnormal
      SPECT study was defined as the presence of fixed and/or reversible perfusion
      defects. End points were cardiac death, nonfatal infarction, and late coronary
      revascularization. A total of 344 (54%) patients had an abnormal SPECT study.
      Perfusion defects included fixed defects alone in 186 patients (29%) and
      reversible defects in 158 (25%) patients. During a mean follow-up of 11.0 +/- 3.3
      years, 174 (27%) patients died (all-cause mortality). Nonfatal myocardial
      infarction occurred in 76 (12%) patients, and late coronary revascularization was
      performed in 194 (30%) patients. Univariable and multivariable Cox proportional
      hazard regression analyses showed that exercise (99m)Tc-tetrofosmin SPECT
      provided prognostic information incremental to clinical data and exercise test
      data. Patients with a normal SPECT had a relatively favorable long-term
      prognosis, in contrast to patients with an abnormal study who had a significantly
      increased risk of cardiac events. The SPECT parameters abnormal scan, reversible
      defect, and summed rest score were strong predictors of long-term outcome.
      CONCLUSION: Exercise (99m)Tc-tetrofosmin myocardial perfusion SPECT has an
      incremental long-term prognostic value over clinical and stress test parameters
      for the prediction of major adverse cardiac events.

PMID- 22875720
TI  - Artificial vortex pinning arrays in superconducting films deposited on highly
      ordered anodic alumina templates.
AB  - A simple procedure is described for creating periodic vortex pinning centers in
      thin superconducting NbN films. We report on three different strategies which
      involve the use of highly ordered alumina templates. In this approach, NbN thin
      films are deposited either on the porous face of the template made of a
      triangular array of nanoholes or on the triangular array of bumps formed by the
      barrier layer or even on the top of perpendicularly oriented ferromagnetic
      nanowire arrays obtained by electrochemical deposition, thus forming
      superconductor-ferromagnet hybrids. In all cases, the ordered template allows NbN
      films to form a periodic pinning array during its growth. The interpore (or inter
      bump) distance ranged between 50 and 100 nm and adjustable pore (or wire)
      diameter was varied between 30 and 60 nm. Numerous matching effects have been
      observed up to 2.5 T and are maintained at low temperature. These fields are
      considerably higher than those typical for periodic pinning arrays made by
      lithographic techniques, which reflects the benefits of nanostructuring
      superconductors by using self-organized growth to enhance vortex pinning in a
      large field and temperature range.

PMID- 22875721
TI  - Effect of narrative reports about vaccine adverse events and bias-awareness
      disclaimers on vaccine decisions: a simulation of an online patient social
      network.
AB  - BACKGROUND: As the number of individuals who search for health information in
      interactive online environments is increasing, patient networks deserve more
      scientific attention. OBJECTIVE: To quantitatively examine if and how reading
      statistical and/or narrative information as typically displayed in patient
      networks (e.g., patientslikeme.com) affects decisions for pharmaceuticals.
      Previous work suggests that narrative information (e.g., about vaccine adverse
      events, VAE) affects risk perceptions and intentions. The authors compare the
      effect of narrative and statistical information about VAE on vaccination
      decisions and examine if a disclaimer reduces the narrative bias as well as if
      low numeracy leads to increased use of the narratives. METHOD AND DESIGN: In an
      online experiment, 458 participants were randomly assigned to a 3 (relative
      frequency of vaccine adverse events in 1, 7, or 17 of 20 cases) * 3 (type of
      information: narratives, summary statistics, or both) * 2 (bias awareness v.
      control disclaimer) between-subjects design. Measurements. Perceived risk,
      vaccination intention, and subjective numeracy. RESULTS: A higher relative
      frequency of cases reporting VAE decreased the intention to get vaccinated. This
      relation was mediated by increased risk perception. The type of information
      moderated the contents' impact: Summary statistics had the smallest impact,
      whereas narrative information was more influential, and the presence of both
      types of information had the greatest impact on risk perception. Individuals who
      received the bias-awareness disclaimer were less influenced by the patient
      network. Highly numerate individuals were generally more sensitive to the
      provided information independent of its format. CONCLUSIONS: Patient networks can
      influence vaccination decisions by delivering risk-related information.
      Disclaimers may help to reduce the influence if desired.

PMID- 22875722
TI  - Prediction of health preference values from CD4 counts in individuals with HIV.
AB  - BACKGROUND: A common measure of health benefit in technology assessments is the
      quality-adjusted life year, which incorporates health preference or utility
      scores. OBJECTIVE: To build and test a predictive model using CD4 counts to
      derive health preference scores. DESIGN: Predictive modeling. Setting. Ontario
      HIV Treatment Network Cohort Study. Measurement. The relationship between HUI3
      derived health preference score and HIV health status measured by CD4 count was
      examined by a regression model. Additional independent variables considered
      included age, time since HIV diagnosis, AIDS-defining condition, sex, and
      education level. A polynomial regression model was fit to predict health
      preference scores. The final model was established using automated backwards
      stepwise variable elimination using the Akaike information criterion. Tenfold
      cross-validation was used to assess the model. RESULTS: Data from 841
      participants were available. Mean age and time since diagnosis were 46.78 and
      11.03 years, respectively. CD4 counts ranged from 2 to 995 cells per mm(3) with
      267 (31.75%) individuals having less than 350 cells per mm(3). Mean HUI3 utility
      score was 0.72 and ranged from -0.25 to 1. The final model retained squared terms
      for CD4 counts, age, and time since HIV diagnosis and eliminated history of AIDS
      defining condition and the nonsquared time since HIV diagnosis. Prediction error
      was assessed in 14 subgroups using the validation set. Two subgroups had mean
      prediction errors greater than 0.02. Limitations. All statistical models are
      limited by the data used to develop and test the model. The model estimates
      health utility scores primarily through CD4 counts. Therefore, the model may be
      inappropriate if noninfectious diseases are a significant factor. CONCLUSIONS:
      Results provide a model for predicting health preference values from CD4 counts.

PMID- 22875724
TI  - Chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) quantify split solid
      objects.
AB  - Recent research suggests that gorillas' and orangutans' object representations
      survive cohesion violations (e.g., a split of a solid object into two halves),
      but that their processing of quantities may be affected by them. We assessed
      chimpanzees' (Pan troglodytes) and bonobos' (Pan paniscus) reactions to various
      fission events in the same series of action tasks modelled after infant studies
      previously run on gorillas and orangutans (Cacchione and Call in Cognition
      116:193-203, 2010b). Results showed that all four non-human great ape species
      managed to quantify split objects but that their performance varied as a function
      of the non-cohesiveness produced in the splitting event. Spatial ambiguity and
      shape invariance had the greatest impact on apes' ability to represent and
      quantify objects. Further, we observed species differences with gorillas
      performing lower than other species. Finally, we detected a substantial age
      effect, with ape infants below 6 years of age being outperformed by both
      juvenile/adolescent and adult apes.

PMID- 22875725
TI  - Experimental evidence for action imitation in killer whales (Orcinus orca).
AB  - Comparative experimental studies of imitative learning have focused mainly on
      primates and birds. However, cetaceans are promising candidates to display
      imitative learning as they have evolved in socioecological settings that have
      selected for large brains, complex sociality, and coordinated predatory tactics.
      Here we tested imitative learning in killer whales, Orcinus orca. We used a 'do
      as-other-does' paradigm in which 3 subjects witnessed a conspecific
      demonstrator's performance that included 15 familiar and 4 novel behaviours. The
      three subjects (1) learned the copy command signal 'Do that' very quickly, that
      is, 20 trials on average; (2) copied 100 % of the demonstrator's familiar and
      novel actions; (3) achieved full matches in the first attempt for 8-13 familiar
      behaviours (out of 15) and for the 2 novel behaviours (out of 2) in one subject;
      and (4) took no longer than 8 trials to accurately copy any familiar behaviour,
      and no longer than 16 trials to copy any novel behaviour. This study provides
      experimental evidence for body imitation, including production imitation, in
      killer whales that is comparable to that observed in dolphins tested under
      similar conditions. These findings suggest that imitative learning may underpin
      some of the group-specific traditions reported in killer whales in the field.

PMID- 22875727
TI  - The works of Dirk Durrer (1918-1984).

PMID- 22875726
TI  - Childhood epilepsy and autism spectrum disorders: psychiatric problems,
      phenotypic expression, and anticonvulsants.
AB  - Epilepsy and autism spectrum disorders (ASDs) frequently co-occur during
      childhood, however, the characteristics of psychiatric or behavioural problems in
      these children remains largely unknown. This article contributes to these
      discussions by reporting on the prevalence and presentation of psychiatric or
      behavioural problems in children with epilepsy and ASDs, as well as on the use of
      anticonvulsants in these children. The current evidence suggests that children
      with epilepsy and ASDs may present with a distinct clinical profile, with a
      greater number of developmental difficulties, and a more severe expression of the
      ASD phenotype that can not solely be accounted for by level of intellectual
      functioning. Positive effects of anticonvulsants on behavioural symptoms
      associated with ASDs were also reported, though pharmacoresistance and a lack of
      clear treatment guidelines may contribute to an elevated risk of adverse side
      effects. In relation to clinical presentation and management there is a need for
      careful consideration of potential interaction effects between disorder specific
      factors (e.g., age of seizure onset/ASD diagnosis), cognitive characteristics
      (e.g., intellectual functioning, memory), and psychosocial variables (e.g.,
      coping strategies). Ultimately however, many conclusions are tentative and this
      review highlights the need for more empirically validated research on children
      with epilepsy and ASDs.

PMID- 22875728
TI  - [Sleep research in Germany].

PMID- 22875729
TI  - [The German centre for lung research - translational research for the prevention,
      diagnosis and treatment of respiratory diseases].
AB  - Respiratory diseases are one of the most important causes of mortality with
      tremendous costs for health care systems, not only in Germany, but worldwide. Up
      to now treatment options for most of these chronic diseases are limited. The
      German Ministry for Research and Education (BMBF) - following the example of the
      US National Institute of Health have supported the foundation of a German Centre
      for Lung Research (DZL) to speed up the development of preventive, diagnostic and
      therapeutic measures. Not only universities, but also non-university based
      research institutes are part of the DZL. To allow the translation from basic
      research experience into clinical practice to improve patient care, basic
      research orientated approaches will be combined with disease and patient focused
      approaches. The DZL is one of six German Centres for Health Care Research
      (neurological diseases, diabetes, cardiovascular diseases, infectious diseases,
      cancer, and lung diseases) for the optimisation of translational processes to
      overcome the burden of major diseases.

PMID- 22875730
TI  - The burden of pneumococcal pneumonia - experience of the German competence
      network CAPNETZ.
AB  - BACKGROUND: Pneumococcal pneumonia is still an important cause of mortality. The
      objective of this study was to compare frequency, clinical presentation, outcome
      and vaccination status of patients with pneumococcal community-acquired pneumonia
      (CAP) to CAP due to other or no detected pathogen based on data of the German
      Network for community-acquired pneumonia (CAPNETZ). METHODS: Demographic,
      clinical and diagnostic data were recorded using standardized web-based data
      acquisition. Standardized microbiological sampling and work-up were conducted in
      each patient. RESULTS: 7400 patients with CAP from twelve clinical centers
      throughout Germany were included. In 2259 patients (32 %) a pathogen was
      identified, Streptococcus pneumonia being the most frequent (n = 676, 30 % of all
      patients with identified pathogens). Compared to those with non-pneumococcal
      pneumonia, patients with pneumococcal pneumonia were more frequently admitted to
      hospital (80 % vs. 66 %, p < 0.001), had higher CURB score values on admission,
      had more frequently pleural effusion (19 % vs. 14 %, p = 0.001) and needed more
      frequently oxygen insufflation (58 % vs. 44 %, p < 0.001). There was no relevant
      difference in overall mortality. CONCLUSIONS: Pneumococcal pneumonia was
      associated with a more severe clinical course demanding more medical resources as
      compared to non-pneumococcal pneumonia.

PMID- 22875731
TI  - [Obstructive sleep apnea and stroke].
AB  - More than half of the patients hospitalised with stroke suffer from sleep
      disordered breathing and 5 - 10 % of patients with newly diagnosed obstructive
      sleep apnea (OSA) have a history of stroke. Epidemiological studies have shown
      that untreated OSA is an independent risk factor for stroke. Various
      pathophysiological mechanisms may contribute to the development of stroke in
      these patients (i. e., OSA-associated arterial hypertension, atherosclerosis,
      atrial fibrillation, paradoxical embolism through a patent foramen ovale and
      disturbed cerebrovascular reactivity). Co-existent OSA has a negative impact on
      both the recovery of neurological functions and the survival of patients with
      stroke. On the other hand, CPAP therapy has beneficial effects on the incidence
      and recurrence of stroke in OSA and also on the clinical outcome of those
      patients who are victims of stroke.

PMID- 22875733
TI  - [The new GOLD document].

PMID- 22875734
TI  - [Do advers health effects of chrysotile and amphibole asbestos differ?].
AB  - Due to the current query whether the predominantly used chrysotile (white)
      asbestos comprises health risks we performed a literature search including in
      vitro and animal experiments as well as epidemiological studies.As shown by
      epidemiological studies chrysotile causes less pleural fibrosis and mesotheliomas
      when compared with other asbestos types. However, its otherwise inflammatory,
      toxic, carcinogenic, and fibrosis-inducing effects correspond to those of other
      occupationally relevant asbestos types. This is based on clinical, animal as well
      as on in-vitro findings. This means that denying a causal relationship, e. g. in
      a case with lung fibrosis (= asbestosis) or lung cancer with an asbestos load of
      25 fiber-years in the absence of identification of a significant concentration of
      asbestos fibers or asbestos bodies in the lung (see so-called "hit and run"
      phenomenon), contradicts the medical-scientific knowledge.

PMID- 22875735
TI  - Characterization of soil bacterial communities in rhizospheric and
      nonrhizospheric soil of Panax ginseng.
AB  - A culture-independent approach was used to evaluate the bacterial community in
      rhizospheric and nonrhizospheric soil in which Panax ginseng had grown for 3
      years. For each sample, soil was randomly collected from multiple sampling points
      and mixed thoroughly before genomic DNA extraction. Universal primers 27f and
      1492r were used to amplify 16S rRNA genes. Clone libraries were constructed using
      the amplified 16S rRNA genes, and 192 white clones were chosen for further
      sequencing. After digestion with restriction endonuclease, 44 operational
      taxonomic units (OTUs) were generated for rhizospheric and 21 OTUs for
      nonrhizospheric soils, and the clones of each OTU were sequenced. Blast analysis
      showed that bacillus, acidobacteria, and proteobacteria were the dominant
      populations in rhizospheric soil, and proteobacteria were dominant in
      nonrhizospheric soil. Phylogenetic results showed that bacillus and acidobacteria
      were clustered into the group of uncultured bacteria in rhizospheric soil;
      however, proteobacteria were the unique dominant in nonrhizospheric soil.

PMID- 22875736
TI  - Impact of intracoronary cell therapy on left ventricular function in the setting
      of acute myocardial infarction: a meta-analysis of randomised controlled clinical
      trials.
AB  - CONTEXT: Numerous randomized controlled studies assessing intracoronary bone
      marrow cell therapy (BMC) after acute myocardial infarction (AMI) have been
      performed. OBJECTIVE: To systematically review the effect of autologous BMC
      therapy on left ventricular function by performing an up to date meta-analysis of
      randomized controlled trials (RCTs) including long-term follow-up. DATA SOURCES:
      Trials were indentified through a literature search from 1980 to June 2012 of the
      Pubmed, Embase, Cochrane database, and the Current Controlled Trials Register.
      STUDY SELECTION: Randomized clinical trials comparing intracoronary BMC infusion
      to control as treatment for AMI. DATA EXTRACTION: The primary endpoint was the
      change in left ventricular ejection fraction (LVEF) from baseline to follow-up.
      Secondary endpoints were changes in left ventricular end diastolic volume
      (LVEDV), left ventricular end systolic volume (LVESV), infarct size and clinical
      outcomes. RESULTS: Improvement of LVEF in patients receiving intracoronary BMC
      was significantly better within 6 months (23 studies, 2.23% (95% confidence
      interval (CI) 1.00 to 3.47); p<0.001). At 12 months of follow-up, this effect
      sustained with 3.91% more LVEF improvement (11 studies, (95% CI 2.56 to 5.27),
      p<0.001). At long-term follow-up, we found a trend for better LVEF improvement in
      favor of cell therapy (7 studies, 1.90% (95% CI -0.43 to 4.23); p=0.11). There
      was no clear effect in infarct size or LVEDV. However, we found a significant
      reduction in LVESV at 6 months (-4.81 ml (95% CI -7.86 to -1.76); p<0.001 and at
      12 months (-9.41 ml (95% CI -13.64 to -5.17); p<0.001). Moreover, there was a
      statistically significant decrease in recurrent AMI (Relative Risk (RR) 0.44 (95%
      CI 0.24 to 0.79); p=0.007), and readmission for heart failure, unstable angina or
      chest pain (RR 0.59 (95% CI 0.35 to 0.98); p=0.04) in favour of cell therapy.
      CONCLUSION: Intracoronary BMC treatment leads to a moderate improvement of LVEF
      and reduction of LVESV at 6 months that sustained at 12 months follow-up, without
      a clear significant effect on LVEDV, or infarct size. Furthermore, we found that
      intracoronary cell therapy is significantly associated with a reduction in
      recurrent AMI and readmission for heart failure, unstable angina or chest pain.

PMID- 22875737
TI  - Peripartum cocaine use and postpartum myocardial infarction.

PMID- 22875738
TI  - Sexual problems in elderly male and female patients with heart failure.
AB  - OBJECTIVES: To investigate perceived sexual problems in a large group of younger
      and older patients with heart failure (HF), with and without a partner, focusing
      on a broad range of perceived sexual problems, and compare this with a sample of
      healthy community-dwelling elderly people. DESIGN: Cross-sectional study.
      SETTING: 17 HF clinics and general practices in The Netherlands. PARTICIPANTS:
      438 patients with HF and 459 healthy community-dwelling elderly people. MAIN
      OUTCOME MEASURES: Differences in sexual functioning, related factors and
      perceived causes of sexual problems between patients with HF and healthy
      community controls. RESULTS: In total, 59% of HF patients reported sexual
      problems, mostly problems with erectile function. HF patients with a partner
      (67%) and younger patients (65%) reported significantly more sexual problems than
      healthy community controls (58%, p=0.011 and 53%, p=0.011, respectively).
      Multivariate analyses show that sexual problems in HF patients with a partner
      were more common in men (OR 2.73, 95% CI 1.572 to 4.753) and in those with a
      prescription of beta-blockers (OR 2.00, 95% CI 1.10 to 3.586). In younger
      patients, sexual problems were independently associated with male gender (OR
      3.21, 95% CI 2.099 to 4.908) and having a partner (OR 2.00, 95% CI 1.283 to
      3.110). HF patients mainly attribute their sexual problems to symptoms of HF.
      CONCLUSION: Sexual problems are common in patients with HF, particularly in
      younger patients and those with a partner. As patients attribute their sexual
      problems mostly to HF symptoms, adequate treatment and education of HF patients
      is needed.

PMID- 22875739
TI  - Drug-induced valvular heart disease.
AB  - Drug-induced valvular heart disease (DIVHD) was first described in the 1960s.
      Initially, associations with ergot derivatives used for migraine prevention, or
      with anorectic drugs, were described. Drugs used for the treatment of Parkinson's
      disease and endocrine diseases, like hyperprolactinemia, may also induce VHD.
      More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and
      benfluorexhave been found to be associated with DIVHD. Although some of these
      drugs were withdrawn from the market, several cases of patients requiring valve
      surgery even years after the cessation of therapy have been reported. DIVHD is
      not infrequent, may be severe, and has been described in association with several
      drugs. Even after drug cessation, long-term implications of this type of VHD may
      persist. The present review underlines the need for a careful evaluation of the
      associated clinical and echocardiographic risk factors to allow early recognition
      so as not to delay appropriate management.

PMID- 22875740
TI  - Asymmetric flow field-flow fractionation of superferrimagnetic iron oxide
      multicore nanoparticles.
AB  - Magnetic nanoparticles are very useful for various medical applications where
      each application requires particles with specific magnetic properties. In this
      paper we describe the modification of the magnetic properties of magnetic
      multicore nanoparticles (MCNPs) by size dependent fractionation. This
      classification was carried out by means of asymmetric flow field-flow
      fractionation (AF4). A clear increase of the particle size with increasing
      elution time was confirmed by multi-angle laser light scattering coupled to the
      AF4 system, dynamic light scattering and Brownian diameters determined by
      magnetorelaxometry. In this way 16 fractions of particles with different
      hydrodynamic diameters, ranging between around 100 and 500 nm, were obtained. A
      high reproducibility of the method was confirmed by the comparison of the mean
      diameters of fractions of several fractionation runs under identical conditions.
      The hysteresis curves were measured by vibrating sample magnetometry. Starting
      from a coercivity of 1.41 kA m(-1) for the original MCNPs the coercivity of the
      particles in the different fractions varied from 0.41 to 3.83 kA m(-1). In our
      paper it is shown for the first time that fractions obtained from a broad size
      distributed MCNP fluid classified by AF4 show a strong correlation between
      hydrodynamic diameter and magnetic properties. Thus we state that AF4 is a
      suitable technology for reproducible size dependent classification of magnetic
      multicore nanoparticles suspended as ferrofluids.

PMID- 22875741
TI  - Tardive dyskinesia after short-term treatment with oral metoclopramide in an
      adolescent.
AB  - CASE: The objective of this case report is to report the development of tardive
      dyskinesia in an African-American adolescent male after short-term treatment with
      metoclopramide 10 mg orally three times daily secondary to delayed gastric
      emptying. The patient developed symptoms of tardive dyskinesia after 2 days of
      therapy with metoclopramide. Metoclopramide was discontinued and diphenhydramine
      50 mg was initially administered intravenously followed with 25 mg orally every 4
      hours as needed. While there are case reports of drug-induced tardive dyskinesia
      after intravenous administration of metoclopramide, this is to our knowledge the
      first report of tardive dyskinesia after short-term treatment with oral
      metoclopramide in an adolescent. CONCLUSION: Awareness of the risk of development
      of this adverse effect even with short-term treatment with metoclopramide and in
      younger patients is important.

PMID- 22875742
TI  - Fusobacterium nucleatum infection mimicking metastatic cancer.
AB  - A 48-year-old man presented with fevers, chills, weight loss, multiple liver
      masses, and several superficial and deep venous thromboses in lower extremities.
      Cancer work up was negative. A liver biopsy grew Fusobacterium nucleatum. To our
      knowledge, F. nucleatum infection presenting with multiple liver masses and
      Trousseau-like syndrome has not been reported earlier.

PMID- 22875743
TI  - Primary empty sella (PES): a review of 175 cases.
AB  - The term primary empty sella (PES) makes reference to the herniation of the
      subarachnoid space within the sella turcica in patients with no history of
      pituitary tumor, surgery or radiotherapy. To retrospectively assess clinical
      features, radiological findings and the biochemical endocrine function from the
      records of 175 patients with a diagnosis of PES. One hundred seventy-five
      patients (150 females) were studied. The mean age at diagnosis was 48.2 +/- 14
      year. Most diagnoses were made by magnetic resonance imaging (n = 172). In most
      patients, the pituitary function was assessed by basal pituitary hormones
      measurements. Pituitary scans were ordered for different reasons: headache (33.1
      %), endocrine disorders (30.6 %), neurological symptoms (12.5 %), visual
      disturbances (8.75 %), abnormalities on sella turcica radiograph (8.75 %) and
      others (6.25 %). Multiple pregnancies were observed in 58.3 % of women;
      headaches, obesity, and hypertension were found in 59.4, 49.5, and 27.3 % of the
      studied population, respectively. Mild hyperprolactinemia (<50 ng/ml) was present
      in 11.6 % of women and 17.3 % of men. Twenty-eight percent of our patients had
      some degree of hypopituitarism. In the male population, hypopituitarism
      represented 64 % of cases, whereas it accounted for 22 % of all females. PES
      seems to be more commonly found in middle-aged women, with a history of multiple
      pregnancies. In most patients, PES was discovered as an incidental finding on
      imaging studies, while in almost a quarter of patients PES was found during the
      diagnostic evaluation of anterior pituitary deficiency, which was more common in
      men.

PMID- 22875745
TI  - Lapatinib, trastuzumab or the combination added to preoperative chemotherapy for
      breast cancer: a meta-analysis of randomized evidence.
AB  - We compared the efficacy and safety of the addition of lapatinib versus
      trastuzumab or their combination to neoadjuvant chemotherapy in HER2-positive
      breast cancer. Potentially eligible trials were located through PubMed and
      Cochrane Library searches and abstracts of major international conferences. The
      endpoints that we assessed were pathologic complete response (pCR) rate, and
      toxicity. Pooled risk ratios (RR) were estimated for each endpoint with fixed or
      random effects models, depending on between studies heterogeneity. Six trials
      were identified with 1,494 eligible patients. The probability to achieve pCR was
      higher for the trastuzumab plus chemotherapy arm versus lapatinib plus
      chemotherapy (RR 1.25, 95 % confidence interval [CI] 1.08-1.43; p = 0.003) (6
      trials; 1,494 patients). Probability to pCR was significantly higher in the group
      receiving lapatinib and trastuzumab than in the group with trastuzumab alone (RR
      1.39, 95 % CI 1.20-1.63; p < 0.001) (4 trials; 779 patients). Grade III-IV
      diarrhea and dermatologic toxicities were statistically more frequent in patients
      receiving lapatinib. No differences were observed regarding cardiac adverse
      events among patients receiving trastuzumab, lapatinib, or their combination.
      These data supports the superiority of a dual-HER2 inhibition for the treatment
      of HER2-positive breast cancer in the neoadjuvant setting. The direct comparison
      of trastuzumab and lapatinib showed that lapatinib is inferior in terms of pCR
      and associated with a higher risk for toxicity.

PMID- 22875744
TI  - Cross-platform pathway-based analysis identifies markers of response to the PARP
      inhibitor olaparib.
AB  - Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. PARP
      inhibitors can act as chemosensitizers, or operate on the principle of synthetic
      lethality when used as single agent. Clinical trials have shown drugs in this
      class to be promising for BRCA mutation carriers. We postulated that inability to
      demonstrate response in non-BRCA carriers in which BRCA is inactivated by other
      mechanisms or with deficiency in homologous recombination for DNA repair is due
      to lack of molecular markers that define a responding subpopulation. We
      identified candidate markers for this purpose for olaparib (AstraZeneca) by
      measuring inhibitory effects of nine concentrations of olaparib in 22 breast
      cancer cell lines and identifying features in transcriptional and genome copy
      number profiles that were significantly correlated with response. We emphasized
      in this discovery process genes involved in DNA repair. We found that the cell
      lines that were sensitive to olaparib had a significant lower copy number of
      BRCA1 compared to the resistant cell lines (p value 0.012). In addition, we
      discovered seven genes from DNA repair pathways whose transcriptional levels were
      associated with response. These included five genes (BRCA1, MRE11A, NBS1, TDG,
      and XPA) whose transcript levels were associated with resistance and two genes
      (CHEK2 and MK2) whose transcript levels were associated with sensitivity. We
      developed an algorithm to predict response using the seven-gene transcription
      levels and applied it to 1,846 invasive breast cancer samples from 8 U133A/plus 2
      (Affymetrix) data sets and found that 8-21 % of patients would be predicted to be
      responsive to olaparib. A similar response frequency was predicted in 536 samples
      analyzed on an Agilent platform. Importantly, tumors predicted to respond were
      enriched in basal subtype tumors. Our studies support clinical evaluation of the
      utility of our seven-gene signature as a predictor of response to olaparib.

PMID- 22875746
TI  - Study of stillbirth and major congenital anomaly among newborns in the high-level
      natural radiation areas of Kerala, India.
AB  - Monitoring newborns for adverse outcomes like stillbirth and major congenital
      anomalies (MCA) is being carried out in government hospitals since 1995 in and
      around high-level natural radiation areas, a narrow strip of land on the
      southwest coast of Kerala, India. Natural deposits of monazite sand containing
      thorium and its daughter products account for elevated levels of natural
      radiation. Among 141,540 newborns [140,558 deliveries: 139,589 singleton, 957
      twins (6.81 0/00), 11 triplets (0.078 0/00), and one quadruplet] screened, 615
      (4.35 0/00) were stillbirth and MCA were seen in 1,370 (9.68 0/00) newborns.
      Clubfoot (404, 2.85 0/00) was the most frequent MCA followed by hypospadias (152,
      2.10 0/00 among male newborns), congenital heart disease (168, 1.19 0/00), cleft
      lip/palate (149, 1.05 0/00), Down syndrome (104, 0.73 0/00), and neural tube
      defects (72, 0.51 0/00). Newborns with MCA among stillbirths were about 20-fold
      higher at 190.24 0/00 (117/615) compared to 8.89 0/00 (1,253/140,925) among live
      births (P < .001). Logistic regression was carried out to compare stillbirth,
      overall, and specific MCA among newborns from areas with dose levels of <=1.5,
      1.51-3.0, 3.01-6.0 and >6 mGy/year after controlling for maternal age at birth,
      gravida, consanguinity, ethnicity, and gender of the baby. Clubfoot showed higher
      prevalence of 3.26 0/00 at dose level of 1.51-3.0 mGy/year compared to 2.33 0/00
      at <=1.5 mGy/year (OR = 1.39; 95 % CI, 1.12-1.72), without indication of any
      clear dose-response. Prevalences of stillbirth, overall MCA, and other specific
      MCA were similar across different dose levels and were relatively lower than that
      reported elsewhere in India, probably due to better literacy, health awareness,
      and practices in the study population.

PMID- 22875747
TI  - An assessment of risk factors for the complexity of coronary artery disease using
      the SYNTAX score.
AB  - In 2005, the SYNTAX score was reported as "an angiographic tool grading the
      complexity of coronary artery disease". We investigated risk factors for the
      complexity of coronary artery disease (CAD) using SYNTAX scores in patients with
      new-onset CAD. The subjects were 359 consecutive cases that underwent de novo
      percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery
      without previous PCI history. Acute myocardial infarction was excluded. The
      SYNTAX scores were obtained from coronary angiographies performed before PCI. On
      multivariate linear regression analysis of risk factors for the SYNTAX scores,
      aging, being a male and having diabetes mellitus were identified as significant
      independent risk factors (age: multiple regression coefficient 0.27, p = 0.001;
      male: 4.91, p = 0.004; diabetes: 4.53, p = 0.001). Other coronary risk factors
      such as hypertension, hypercholesterolemia, smoking and reduced renal function
      were not identified as significant independent risk factors. In patients
      undergoing PCI, aging, being a male and having diabetes mellitus are considered
      to be independent risk factors for the complexity of CAD. Therefore, when
      patients with CAD have these factors, we expect the CAD of the patient to be more
      complex and that it will be necessary to provide more careful medical care.

PMID- 22875748
TI  - Percutaneous coronary intervention through unintentional sheath placement in the
      inferior epigastric artery.
AB  - A 64 year old female underwent percutaneous coronary intervention (PCI) with
      stent placement through the femoral approach. On femoral angiography after the
      PCI, the arterial sheath insertion site was found to be in the inferior
      epigastric artery and not in the common femoral artery. We used an Angioseal
      vascular closure device for management and there were no access site
      complications.

PMID- 22875750
TI  - Perineal powder use and risk of endometrial cancer in postmenopausal women.
AB  - BACKGROUND: Most known endometrial cancer risk factors involve genetics or
      exposure to unopposed estrogens; less is known about risk due to environmental
      exposures. While several studies have found an increased risk of ovarian cancer
      associated with perineal powder use, only two studies have addressed perineal
      powder use and endometrial cancer risk. METHODS: We used Cox proportional hazards
      regression to examine the association between perineal powder use and endometrial
      cancer risk using the Women's Health Initiative Observational Study Research
      Materials obtained from the National Heart, Lung, and Blood Institute Biological
      Specimen and Data Repository Coordinating Center. RESULTS: Of the 48,526 women in
      our primary analysis, 25,181 (52 %) reported ever use of perineal powder. During
      364,134 person-years of follow-up, 447 participants were diagnosed with
      endometrial cancer. Ever use of perineal powder was not associated with increased
      risk of endometrial cancer (multivariable-adjusted hazard ratio, 1.06; 95 %
      confidence interval, 0.87-1.28). External use of powder on the genitals and/or on
      sanitary napkins was also not significantly associated with risk of endometrial
      cancer. However, use of powder on a diaphragm for twenty or more years was
      associated with a threefold increase in risk of endometrial cancer compared to
      women who never used perineal powder (multivariable-adjusted hazard ratio, 3.06;
      95 % CI, 2.00-4.70). CONCLUSIONS: Any duration of external use of perineal powder
      was not associated with increased risk of endometrial cancer; however, long-term
      use of powder on a diaphragm may increase the risk of endometrial cancer.

PMID- 22875749
TI  - OsWRKY30 is activated by MAP kinases to confer drought tolerance in rice.
AB  - Both the WRKY transcription factor (TF) and MAP kinases have been shown to
      regulate gene expression in response to biotic and abiotic stresses in plants.
      Several reports have shown that WRKY TFs may function downstream of MAPK
      cascades. Here, we have shown that OsWRKY30 interacted with OsMPK3, OsMPK4,
      OsMPK7, OsMPK14, OsMPK20-4, and OsMPK20-5, and could be phosphorylated by OsMPK3,
      OsMPK7, and OsMPK14. Overexpression of OsWRKY30 in rice dramatically increased
      drought tolerance. Overexpression of OsWRKY30AA, in which all SP (serine residue
      followed by proline residue) sites were replaced by AP (A, alanine), resulted in
      no improvement in drought tolerance. In addition, the function of transcriptional
      activation of OsWRKY30 was impaired after SP was replaced by AP. These results
      proved that the phosphorylation of OsWRKY30 by MAPKs was crucial in order for
      OsWRKY30 to perform its biological function.

PMID- 22875751
TI  - Understanding the properties of common dietary supplements: clinical implications
      for healthcare practitioners.
AB  - BACKGROUND: Dietary supplement usage in the United States continues to increase.
      This article explores the background of dietary supplements and their
      regulations, discusses trends in usage patterns highlighting the properties of 10
      popular dietary supplements, addresses safety concerns and drug-nutrient
      interactions, and discusses the role of the healthcare professional in assessing
      and recommending usage of dietary supplements. METHODS: The authors reviewed the
      literature on dietary supplementation. Government websites were used to obtain
      background and regulatory information. Evidence-based databases were used to
      summarize popular dietary supplements in terms of their common uses, mechanisms
      of action, and clinical implications. The related literature was reviewed to
      discuss important factors for the healthcare professional to consider as well as
      the role of the healthcare professional in integrating dietary supplement use
      within patient care. CONCLUSION: Healthcare professionals need to be prepared to
      evaluate dietary supplement usage and make appropriate recommendations for an
      individualized plan of care. CLINICAL IMPLICATIONS: As the popularity of dietary
      supplements continues to grow, healthcare professionals will need to communicate
      with patients about their usage; educate themselves on their potential benefits,
      interactions, and contraindications; evaluate the literature; make
      recommendations; and document appropriately in a comprehensive and integrated
      plan of care.

PMID- 22875752
TI  - Perioperative nutrition support in cancer patients.
AB  - Malnutrition and weight loss negatively affect outcomes in surgical cancer
      patients. Decades of research have sought to identify the most appropriate use of
      nutrition support in these patients. National and international guidelines help
      to direct clinicians' use of nutrition support in surgical patients, but a number
      of specific issues concerning the use of nutrition support continue to evolve.
      This review focuses on 5 key issues related to perioperative nutrition support in
      cancer patients: (1) Which perioperative cancer patients should receive nutrition
      support? (2) How can the nutrition status and requirements of these patients be
      optimally assessed? (3) What is the optimal route of administration (parenteral
      nutrition vs enteral nutrition) and composition of nutrition support in this
      setting? (4) When should feedings be initiated? (5) What is the role of glycemic
      control in these patients?

PMID- 22875753
TI  - The "case-chaos study" as an adjunct or alternative to conventional case-control
      study methodology.
AB  - Case-control studies are important in infectious disease epidemiology for rapidly
      identifying and controlling risks, but challenges, including the need for speed,
      can place practical restrictions on control selection and recruitment. The biased
      comparisons that result can hamper or, worse, mislead investigators. Following a
      2009 outbreak of Shiga-like toxin-producing Escherichia coli O157 infection
      associated with a petting farm in southeast England, it was hypothesized that
      case behavior alone could be used to identify risks. Case-patients' exposures
      were randomized on a case-by-case basis, and the resulting permuted data were
      compared with the actual events preceding illness by conditional logistic
      regression analysis. There was good agreement between the risks identified by
      using our new method and the risks elicited in the original outbreak case-control
      studies. This was also the case in analysis of 2 further historical outbreaks.
      These initial findings suggest that the technique, which we have called the "case
      chaos" technique, appeared to be useful in this setting. Analysis of simulated
      data supports this view. Circumventing the need for traditional control data has
      the potential to reduce outbreak investigation lead times, leading to earlier
      interventions and reduced morbidity and mortality. However, further validation is
      necessary, coupled with an awareness of limitations of the method.

PMID- 22875754
TI  - Intake of fruits and vegetables and risk of pancreatic cancer in a pooled
      analysis of 14 cohort studies.
AB  - Fruit and vegetable intake may protect against pancreatic cancer, since fruits
      and vegetables are rich in potentially cancer-preventive nutrients. Most case
      control studies have found inverse associations between fruit and vegetable
      intake and pancreatic cancer risk, although bias due to reporting error cannot be
      ruled out. In most prospective studies, inverse associations have been weaker and
      imprecise because of small numbers of cases. The authors examined fruit and
      vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14
      prospective studies from North America, Europe, and Australia (study periods
      between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were
      estimated separately for the 14 studies using the Cox proportional hazards model
      and were then pooled using a random-effects model. Of 862,584 men and women
      followed for 7-20 years, 2,212 developed pancreatic cancer. The pooled
      multivariate relative risks of pancreatic cancer per 100-g/day increase in intake
      were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and
      vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99,
      1.06) for total vegetables. Associations were similar for men and women
      separately and across studies. These results suggest that fruit and vegetable
      intake during adulthood is not associated with a reduced pancreatic cancer risk.

PMID- 22875755
TI  - Interpreting incremental value of markers added to risk prediction models.
AB  - The discrimination of a risk prediction model measures that model's ability to
      distinguish between subjects with and without events. The area under the receiver
      operating characteristic curve (AUC) is a popular measure of discrimination.
      However, the AUC has recently been criticized for its insensitivity in model
      comparisons in which the baseline model has performed well. Thus, 2 other
      measures have been proposed to capture improvement in discrimination for nested
      models: the integrated discrimination improvement and the continuous net
      reclassification improvement. In the present study, the authors use mathematical
      relations and numerical simulations to quantify the improvement in discrimination
      offered by candidate markers of different strengths as measured by their effect
      sizes. They demonstrate that the increase in the AUC depends on the strength of
      the baseline model, which is true to a lesser degree for the integrated
      discrimination improvement. On the other hand, the continuous net
      reclassification improvement depends only on the effect size of the candidate
      variable and its correlation with other predictors. These measures are
      illustrated using the Framingham model for incident atrial fibrillation. The
      authors conclude that the increase in the AUC, integrated discrimination
      improvement, and net reclassification improvement offer complementary information
      and thus recommend reporting all 3 alongside measures characterizing the
      performance of the final model.

PMID- 22875756
TI  - Further insight into the incremental value of new markers: the interpretation of
      performance measures and the importance of clinical context.
AB  - In this issue of the Journal, Pencina and et al. (Am J Epidemiol. 2012;176(6):492
      494) examine the operating characteristics of measures of incremental value.
      Their goal is to provide benchmarks for the measures that can help identify the
      most promising markers among multiple candidates. They consider a setting in
      which new predictors are conditionally independent of established predictors. In
      the present article, the authors consider more general settings. Their results
      indicate that some of the conclusions made by Pencina et al. are limited to the
      specific scenarios the authors considered. For example, Pencina et al. observed
      that continuous net reclassification improvement was invariant to the strength of
      the baseline model, but the authors of the present study show this invariance
      does not hold generally. Further, they disagree with the suggestion that such
      invariance would be desirable for a measure of incremental value. They also do
      not see evidence to support the claim that the measures provide complementary
      information. In addition, they show that correlation with baseline predictors can
      lead to much bigger gains in performance than the conditional independence
      scenario studied by Pencina et al. Finally, the authors note that the motivation
      of providing benchmarks actually reinforces previous observations that the
      problem with these measures is they do not have useful clinical interpretations.
      If they did, researchers could use the measures directly and benchmarks would not
      be needed.

PMID- 22875757
TI  - Pencina et al. respond to "The incremental value of new markers" and "Clinically
      relevant measures? A note of caution".

PMID- 22875758
TI  - Clinical utility in evaluation of risk models.

PMID- 22875759
TI  - Clinically relevant measures of fit? A note of caution.
AB  - Risk reclassification methods have become popular in the medical literature as a
      means of comparing risk prediction models. In this issue of the Journal, Pencina
      et al. (Am J Epidemiol. 2012;176(6):492-494) present further results for
      continuous measures of model discrimination and describe their characteristics in
      nested models with normally distributed variables. Measures include the change in
      the area under the receiver operating characteristic curve, the integrated
      discrimination improvement, and the continuous net reclassification improvement.
      Although theoretically interesting, these continuous measures may not be the most
      appropriate to assess clinical utility. The continuous net reclassification
      improvement, in particular, is a measure of effect rather than model improvement
      and can sometimes exhibit erratic behavior, as illustrated in 2 examples. Caution
      is needed before using this as a measure of improvement. Further, the test of the
      continuous net reclassification improvement and that for the integrated
      discrimination improvement are similar to the likelihood ratio test in nested
      models and may be overinterpreted. Reclassification in risk strata, while
      requiring thresholds, may be more relevant clinically with its ability to examine
      potential changes in treatment decisions.

PMID- 22875760
TI  - Childhood osteomyelitis: imaging characteristics.
AB  - BACKGROUND: The purpose of this review is to illustrate the imaging findings of
      childhood osteomyelitis. The diagnosis of childhood osteomyelitis can be
      challenging. Clinical presentation and laboratory results can differ and are
      relatively unreliable. To date, its role in the assessment of treatment efficacy
      is not yet clear. METHODS: This review article provides an overview of the
      different imaging modalities and imaging characteristics of childhood
      osteomyelitis. Levels of evidence for different modalities are presented.
      RESULTS: Paediatric radiology plays a pivotal role in the diagnosis of childhood
      osteomyelitis and can also be used to guide therapy and intervention. CONCLUSION:
      Although imaging is essential in the diagnostic process, cooperation between the
      physician and radiologist remains the cornerstone in accurately diagnosing
      childhood osteomyelitis. MAIN MESSAGES: * Imaging plays a pivotal role in the
      diagnosis of childhood osteomyelitis. * Cooperation between the clinician and
      radiologist is a very important aspect of making the diagnosis. * The initial
      imaging modality in childhood osteomyelitis is conventional imaging. * Normal
      conventional imaging does not exclude osteomyelitis.

PMID- 22875761
TI  - Woodstock 2012: a homage to Chris Wood.

PMID- 22875762
TI  - Evolution of high duty cycle echolocation in bats.
AB  - Duty cycle describes the relative 'on time' of a periodic signal. In bats, we
      argue that high duty cycle (HDC) echolocation was selected for and evolved from
      low duty cycle (LDC) echolocation because increasing call duty cycle enhanced the
      ability of echolocating bats to detect, lock onto and track fluttering insects.
      Most echolocators (most bats and all birds and odontocete cetaceans) use LDC
      echolocation, separating pulse and echo in time to avoid forward masking. They
      emit short duration, broadband, downward frequency modulated (FM) signals
      separated by relatively long periods of silence. In contrast, bats using HDC
      echolocation emit long duration, narrowband calls dominated by a single constant
      frequency (CF) separated by relatively short periods of silence. HDC bats
      separate pulse and echo in frequency by exploiting information contained in
      Doppler-shifted echoes arising from their movements relative to background
      objects and their prey. HDC echolocators are particularly sensitive to amplitude
      and frequency glints generated by the wings of fluttering insects. We hypothesize
      that narrowband/CF calls produced at high duty cycle, and combined with
      neurobiological specializations for processing Doppler-shifted echoes, were
      essential to the evolution of HDC echolocation because they allowed bats to
      detect, lock onto and track fluttering targets. This advantage was especially
      important in habitats with dense vegetation that produce overlapping, time
      smeared echoes (i.e. background acoustic clutter). We make four specific,
      testable predictions arising from this hypothesis.

PMID- 22875763
TI  - Determining rates of epithelial solute transport by optical measurement of
      fluorochrome concentration gradients in the unstirred layer.
AB  - We describe a method for calculating rates of fluorochrome transport from
      unstirred layer (USL) concentration gradients measured using confocal microscopy.
      Isolated Malpighian tubules or guts of Drosophila melanogaster were secured to
      depression slides and bathed in saline containing a fluorescent compound. By
      measuring the concentration gradient of fluorescent organic anions (fluorescein,
      Texas Red) or the P-glycoprotein substrate daunorubicin in the USL adjacent to
      the epithelium we were able to calculate the transepithelial flux of the
      fluorochrome using Fick's equation. Dose-response curves for fluorescein and
      Texas Red based on USL concentration gradients near the surface of the Malpighian
      tubule were comparable to those based on collection and analysis of secreted
      fluid droplets. Rates of Texas Red and daunorubicin secretion were also
      calculated for the gut of second instar D. melanogaster larvae, a tissue that is
      too small for measurement of transport rates by other in vitro techniques such as
      cannulation and perfusion. Our results suggest that measurement of USL
      concentration gradients by confocal microscopy may be applicable to any
      fluorescent indicator of rapidly transported compounds.

PMID- 22875764
TI  - Bilateral coordination and the motor basis of female preference for sexual
      signals in canary song.
AB  - The preference of female songbirds for particular traits in the songs of courting
      males has received considerable attention, but the relationship of preferred
      traits to male quality is poorly understood. Female domestic canaries (Serinus
      canaria, Linnaeus) preferentially solicit copulation with males that sing special
      high repetition rate, wide-band, multi-note syllables, called 'sexy' or A
      syllables. Syllables are separated by minibreaths but each note is produced by
      pulsatile expiration, allowing high repetition rates and long duration phrases.
      The wide bandwidth is achieved by including two notes produced sequentially on
      opposite sides of the syrinx, in which the left and right sides are specialized
      for low or high frequencies, respectively. The emphasis of low frequencies is
      facilitated by a positive relationship between syllable repetition rate and the
      bandwidth of the fundamental frequency of notes sung by the left syrinx, such
      that bandwidth increases with increasing syllable repetition rate. The temporal
      offset between notes prevents cheating by unilaterally singing a note on the left
      side with a low fundamental frequency and prominent higher harmonics. The
      syringeal and respiratory motor patterns by which sexy syllables are produced
      support the hypothesis that these syllables provide a sensitive vocal-auditory
      indicator of a male's performance limit for the rapid, precisely coordinated
      interhemispheric switching, which is essential for many sensory and motor
      processes involving specialized contributions from each cerebral hemisphere.

PMID- 22875765
TI  - A model based on oscillatory threshold and build-up of a developmental substance
      explains gating of adult emergence in Drosophila melanogaster.
AB  - Adult emergence (eclosion) of fruit flies Drosophila melanogaster under constant
      laboratory conditions follows a circadian pattern with bouts of eclosion
      recurring at approximately 24 h intervals. Under periodic light:dark (LD) cycles,
      adults emerge only during a specific time of the day followed by little or no
      emergence for the rest of the day. This phenomenon is therefore equated to a gate
      of emergence that, when open, allows adults to emerge and when closed, no
      emergence takes place. In this study, we attempt to understand the mechanism
      underlying adult emergence rhythm in D. melanogaster using a model based on
      interplay between developmental and circadian clock systems. The model is
      composed of an oscillatory threshold of a substance that builds up during pre
      adult development. Computer simulations based on this model enabled us to make
      specific predictions about the 'gate width' of the adult emergence rhythm under
      conditions of fast/slow pre-adult development and short/long circadian periods,
      which we subsequently tested empirically. The main predictions from the
      simulations are: (1) flies with faster development have greater gate width and
      vice versa, and (2) flies with faster circadian clocks have shorter gate width
      and vice versa. To empirically validate these predictions, we carried out
      experiments on D. melanogaster populations known to have fast/slow pre-adult
      development, short/long circadian periods and narrow/wide gate width.
      Additionally, we manipulated the rate of pre-adult development of the above flies
      by increasing/decreasing ambient temperature to further examine the influence of
      developmental rates on gate width of adult emergence rhythm by a complementary
      approach. The results show that gate width is greatly influenced by the duration
      of pre-adult development and the length of circadian cycles. This suggests that
      the adult emergence rhythm of D. melanogaster may be based on mechanisms
      involving oscillatory threshold and build-up of a developmental substance.

PMID- 22875766
TI  - Serotonin-induced brain glycogenolysis in rainbow trout (Oncorhynchus mykiss).
AB  - In this study, we evaluated the serotonin-mediated control of cerebral glycogen
      levels in the rainbow trout, Oncorhynchus mykiss. Intracerebroventricular
      (i.c.v.) administration of serotonin (5-HT) to normoglycemic trout (time and dose
      response) decreased glycogen levels in the brain and increased brain glycogen
      phosphorylase activity (time response). In hypoglycemic fish (that had been
      fasted for 5 and 10 days), there was a time-dependent decrease in brain glycogen
      levels; under these conditions, i.c.v. administration of 5-HT also reduced the
      brain glycogen content in fish that had been fasted for 5 days. In fish with
      local cerebral hypoglycemia (induced by 2-DG administration), the glycogen levels
      decreased and, as above, i.c.v. administration of 5-HT also lowered the glycogen
      content. In hyperglycemic fish, 5-HT did not affect glycogen levels.
      Administration of receptor agonists 5-HT1A (8-OH-DPAT), 5-HT1B (anpirtoline and
      CP93129) or 5-HT2 (alpha-m-5-HT) decreased the brain glycogen levels. This effect
      was antagonized by the administration of receptor antagonists 5-HT1A (WAY100135
      and NAN190), 5-HT1B (NAS181) and 5-HT2B/C (SB206553). Administration of the
      receptor agonists (+/-)-DOI (5-HT2A/2C), m-CPP (5-HT2B/2C), BW723C86 (5-HT2B) and
      WAY 161503 (5-HT2C) led to decreases in the levels of brain glycogen. We found
      that 5-HT is involved in the modulation of brain glycogen homeostasis in the
      rainbow trout, causing a glycogenolytic effect when fish are in a normoglycemic
      or hypoglycemic state, but not when they are in a hyperglycemic state. 5-HT1A, 5
      HT1B, 5HT2B and 5-HT2C-like receptors appeared to be involved in the
      glycogenolytic action of 5-HT, although the effect mediated by 5-HT1A or 5-HT1B
      was apparently stronger.

PMID- 22875767
TI  - Forelimb muscle activity during equine locomotion.
AB  - Few quantitative data exist to describe the activity of the distal muscles of the
      equine forelimb during locomotion, and there is an incomplete understanding of
      the functional roles of the majority of the forelimb muscles. Based on morphology
      alone it would appear that the larger proximal muscles perform the majority of
      work in the forelimb, whereas the smaller distal muscles fulfil supplementary
      roles such as stabilizing the joints and positioning the limb for impact with the
      ground. We measured the timing and amplitude of the electromyographic activity of
      the intrinsic muscles of the forelimb in relation to the phase of gait (stance
      versus swing) and the torque demand placed on each joint during walking, trotting
      and cantering. We found that all forelimb muscles, except the extensor carpi
      radialis (ECR), were activated just prior to hoof-strike and deactivated during
      stance. Only the ECR was activated during swing. The amplitudes of muscle
      activation typically increased as gait speed increased. However, the amplitudes
      of muscle activation were not proportional to the net joint torques, indicating
      that passive structures may also contribute significantly to torque generation.
      Our results suggest that the smaller distal muscles help to stabilize the
      forelimb in early stance, in preparation for the passive structures (tendons and
      ligaments) to be stretched. The distal forelimb muscles remain active throughout
      stance only during canter, when the net torques acting about the distal forelimb
      joints are highest. The larger proximal muscles activate in a complex
      coordination to position and stabilize the shoulder and elbow joints during
      ground contact.

PMID- 22875768
TI  - Underwater hearing in the loggerhead turtle (Caretta caretta): a comparison of
      behavioral and auditory evoked potential audiograms.
AB  - The purpose of this study was to compare underwater behavioral and auditory
      evoked potential (AEP) audiograms in a single captive adult loggerhead sea turtle
      (Caretta caretta). The behavioral audiogram was collected using a go/no-go
      response procedure and a modified staircase method of threshold determination.
      AEP thresholds were measured using subdermal electrodes placed beneath the
      frontoparietal scale, dorsal to the midbrain. Both methods showed the loggerhead
      sea turtle to have low frequency hearing with best sensitivity between 100 and
      400 Hz. AEP testing yielded thresholds from 100 to 1131 Hz with best sensitivity
      at 200 and 400 Hz (110 dB re. 1 MUPa). Behavioral testing using 2 s tonal stimuli
      yielded underwater thresholds from 50 to 800 Hz with best sensitivity at 100 Hz
      (98 dB re. 1 MUPa). Behavioral thresholds averaged 8 dB lower than AEP thresholds
      from 100 to 400 Hz and 5 dB higher at 800 Hz. The results suggest that AEP
      testing can be a good alternative to measuring a behavioral audiogram with wild
      or untrained marine turtles and when time is a crucial factor.

PMID- 22875769
TI  - Locomotory activity and feeding strategy of the hadal munnopsid isopod Rectisura
      cf. herculea (Crustacea: Asellota) in the Japan Trench.
AB  - Benthic fauna in the hadal zone (6500-11,000 m) rely on maintaining sufficient
      locomotory activity to exploit a low, patchy and uniquely distributed food supply
      while exposed to high pressure, low temperatures and responding to predator-prey
      interactions. Very little is currently known about the locomotory capabilities of
      hadal fauna. In situ video footage of the isopod Rectisura cf. herculea (Birstein
      1957) (Asellota, Munnopsidae) was obtained from 6945 and 7703 m deep in the Japan
      Trench (NW Pacific Ocean). Measurements of locomotion revealed routine walking
      speeds of 0.19 +/- 0.04 BL s(-1) (mean +/- s.d.), increasing to 0.33 +/- 0.04 BL
      s(-1) if naturally perturbed by larger organisms. When immediately threatened by
      the presence of predators (decapod crustaceans), the isopods are capable of
      eliciting backward escape jumps and burst swimming escape responses of 2.6 +/-
      1.5 BL s(-1) and 4.63 +/- 0.9 BL s(-1), respectively. These data suggest no
      significant reduction in locomotory capability despite the extreme depths in
      which they inhabit. These observations also revealed the isopod to be a bait
      attending and aggregative species and suggest that it may not be obligatorily
      selecting infaunal food sources as previously thought.

PMID- 22875770
TI  - New model for gain control of signal intensity to object distance in echolocating
      bats.
AB  - Echolocating bats emit ultrasonic calls and listen for the returning echoes to
      orient and localize prey in darkness. The emitted source level, SL (estimated
      signal intensity 10 cm from the mouth), is adjusted dynamically from call to call
      in response to sensory feedback as bats approach objects. A logarithmic
      relationship of SL=20 log(10)(x), i.e. 6 dB output reduction per halving of
      distance, x, has been proposed as a model for the relationship between emitted
      intensity and object distance, not only for bats but also for echolocating
      toothed whales. This logarithmic model suggests that the approaching echolocator
      maintains a constant intensity impinging upon the object, but it also implies
      ever-increasing source levels with distance, a physical and biological
      impossibility. We developed a new model for intensity compensation with an
      exponential rise to the maximum source level: SL=SL(max)-ae(-)(bx). In addition
      to providing a method for estimating maximum output, the new model also offers a
      tool for estimating a minimum detection distance where intensity compensation
      starts. We tested the new exponential model against the 'conventional'
      logarithmic model on data from five bat species. The new model performed better
      in 77% of the trials and as good as the conventional model in the rest (23%). We
      found much steeper rates of compensation when fitting the model to individual
      rather than pooled data, with slopes often steeper than -20 dB per halving of
      distance. This emphasizes the importance of analyzing individual events. The
      results are discussed in light of habitat constraints and the interaction between
      bats and their eared prey.

PMID- 22875771
TI  - Leg adjustments during running across visible and camouflaged incidental changes
      in ground level.
AB  - During running in a natural environment, humans must routinely negotiate varied
      and unpredictable changes in ground level. To prevent a fall, changes in ground
      level, especially those that are invisible, require a quick response of the
      movement system within a short time. For 11 subjects we investigated two
      consecutive contacts during running across visible (drop of 0, 5 and 10 cm) and
      camouflaged (drop of 0 and 10 cm) changes in ground level. For both situations,
      we found significant variances in their leg parameters and ground reaction forces
      (GRFs) during the perturbed second contact but also one step ahead, in the
      unperturbed first contact. At visible first contact, humans linearly adapt their
      GRF to lower and smooth their centre of mass. During the camouflaged situation,
      the GRF also decreased, but it seems that the runners anticipate a drop of
      approximately 5-10 cm. The GRF increased with drop height during the visible
      perturbed second contact. At the camouflaged second contact, GRFs differed
      noticeably from the observed reaction when crossing a similar visible drop,
      whereas the contact time decreased and the initial impact peak increased. This
      increased impact can be interpreted as a purely mechanical contribution to cope
      with the event. Furthermore, we observed an increased angle of attack and leg
      length with drop height for both situations. This is in accordance with results
      observed in birds running over a track with an unexpected drop, and suggests that
      adaptations in swing leg retraction form part of the strategy for running across
      uneven ground.

PMID- 22875772
TI  - The effect of surface water and wetting on gecko adhesion.
AB  - Despite profound interest in the mechanics and performance of the gecko adhesive
      system, relatively few studies have focused on performance under conditions that
      are ecologically relevant to the natural habitats of geckos. Because geckos are
      likely to encounter surfaces that are wet, we used shear force adhesion
      measurements to examine the effect of surface water and toe pad wetting on the
      whole-animal performance of a tropical-dwelling gecko (Gekko gecko). To test the
      effect of surface wetting, we measured the shear adhesive force of geckos on
      three substrate conditions: dry glass, glass misted with water droplets and glass
      fully submerged in water. We also investigated the effect of wetting on the
      adhesive toe pad by soaking the toe pads prior to testing. Finally, we tested for
      repeatability of the adhesive system in each wetting condition by measuring shear
      adhesion after each step a gecko made under treatment conditions. Wetted toe pads
      had significantly lower shear adhesive force in all treatments (0.86 +/- 0.09 N)
      than the control (17.96 +/- 3.42 N), as did full immersion in water (0.44 +/-
      0.03 N). Treatments with droplets of water distributed across the surface were
      more variable and did not differ from treatments where the surface was dry (4.72
      +/- 1.59 N misted glass; 9.76 +/- 2.81 N dry glass), except after the gecko took
      multiple steps. These findings suggest that surface water and the wetting of a
      gecko's adhesive toe pads may have significant consequences for the ecology and
      behavior of geckos living in tropical environments.

PMID- 22875773
TI  - Hepatic confinement of newly produced erythrocytes caused by low-temperature
      exposure in Xenopus laevis.
AB  - Diminished erythrocyte count and erythropoiesis have been reported during
      hypothermia in some ectothermic animals. In this study, the African clawed frog,
      Xenopus laevis, was used to investigate the cause of hypothermia-induced anemia.
      We developed a new model of hypothermia at 5 degrees C and monitored blood cell
      count and erythropoiesis on several days. Erythrocyte count declined by 30% on
      the first day following cold exposure (5 degrees C) and mRNA expression of
      hemeoxygenase-1 was enhanced 10-fold; accumulation of iron as a result of heme
      degradation was observed in the liver. One day after low-temperature exposure,
      erythropoietin mRNA expression was elevated in the liver and lung compared with
      that at normal temperature (22 degrees C) by qRT-PCR analysis. Examination of
      liver sections (i.e. the erythropoietic organ) showed an increase in o
      dianisidine-positive erythrocytes in the hepatic sinusoid 5 days after the onset
      of low-temperature exposure compared with normal liver. Peripheral erythrocyte
      count remained low, indicating that newly produced erythrocytes did not migrate
      from the liver to the circulation during hypothermia. In conclusion, this study
      reveals hypothermic anemia as being associated with hepatic erythrocyte
      destruction; prolonged anemia during low-temperature exposure is concomitant with
      newly produced erythrocytes being confined to the liver and may lead to new
      insights into vertebrate hematopoiesis.

PMID- 22875774
TI  - Glycogen, not dehydration or lipids, limits winter survival of side-blotched
      lizards (Uta stansburiana).
AB  - Climate change is causing winters to become milder (less cold and shorter).
      Recent studies of overwintering ectotherms have suggested that warmer winters
      increase metabolism and decrease winter survival and subsequent fecundity.
      Energetic constraints (insufficient energy stores) have been hypothesized as the
      cause of winter mortality but have not been tested explicitly. Thus, alternative
      sources of mortality, such as winter dehydration, cannot be ruled out. By
      employing an experimental design that compared the energetics and water content
      of lizards that died naturally during laboratory winter with those that survived
      up to the same point but were then sacrificed, we attempt to distinguish among
      multiple possible causes of mortality. We test the hypothesis that mortality is
      caused by insufficient energy stores in the liver, abdominal fat bodies, tail or
      carcass or through excessive water loss. We found that lizards that died
      naturally had marginally greater mass loss, lower water content, and less liver
      glycogen remaining than living animals sampled at the same time. Periodically
      moistening air during winter reduced water loss, but this did not affect
      survival, calling into question dehydration as a cause of death. Rather, our
      results implicate energy limitations in the form of liver glycogen, but not
      lipids, as the primary cause of mortality in overwintering lizards. When viewed
      through a lens of changing climates, our results suggest that if milder winters
      increase the metabolic rate of overwintering ectotherms, individuals may
      experience greater energetic demands. Increased energy use during winter may
      subsequently limit individual survival and possibly even impact population
      persistence.

PMID- 22875775
TI  - Plagiarism.

PMID- 22875776
TI  - Eight-vessel disease mimicking takotsubo cardiomyopathy.

PMID- 22875777
TI  - A lung cancer masquerader.

PMID- 22875778
TI  - Bites in Australian snake handlers--Australian snakebite project (ASP-15).
AB  - BACKGROUND: Snakebites in snake handlers are an important clinical problem that
      may differ to bites in the general population. AIM: To investigate the
      epidemiology and clinical presentation of bites in snake handlers. DESIGN:
      Prospective observational study. METHODS: Bites in snake handlers recruited as
      part of the Australian Snakebite Project (ASP) from 2004 to 2011 were included in
      the study. Data were extracted from the ASP database, which included demographic
      and clinical information, laboratory tests and antivenom treatment. RESULTS: From
      1089 snake bites recruited to ASP, there were 106 (9.7%) bites in snake handlers.
      The median age was 40 years (range: 16-81 years) and 104 (98%) were males. The
      commonest circumstances of the bites were handling snakes (47), catching snakes
      (22), feeding snakes (18) and cleaning cages (11). Bites were to the upper limb
      in 103 cases. Bites were most commonly by Red-bellied black snakes (20), Brown
      snakes (17), Taipan (15), Tiger snakes (14) and Death adders (14). Envenoming
      occurred in 77 patients: venom-induced consumption coagulopathy in 45 patients
      (58%), neurotoxicity in 10 (13%) and myotoxicity in 13 (17%). Systemic
      hypersensitivity reactions (SHSRs) to venom occurred in eight, satisfying
      clinical criteria for anaphylaxis in five, of which three were hypotensive.
      Antivenom was administered in 60 envenomed patients. SHSRs to antivenom occurred
      in 15 (25%; 95% CI:15-38%), including 2 (3%:1-13%) with severe (hypotensive)
      reactions. CONCLUSION: Bites in snake handlers remain a common, important problem
      involving a broad range of snakes. Neurotoxicity and myotoxicity are relatively
      common, consistent with the snakes involved. Venom anaphylaxis occured, despite
      previously being a poorly recognized problem in snake handlers. The incidence of
      SHSRs to antivenoms, including anaphylaxis, was not higher than that observed in
      non-snake handlers.

PMID- 22875779
TI  - Adult Kawasaki disease.

PMID- 22875780
TI  - The effect of treating institution on outcomes in head and neck cancer.
AB  - OBJECTIVE: Factors leading patients with head and neck cancer (HNCA) to seek
      radiation or chemoradiation in an academic center versus the community are
      incompletely understood, as are the effects of site of treatment on treatment
      completion and survival. STUDY DESIGN: Historical cohort study. SETTING: Tertiary
      academic center, community practices. METHODS: A historical cohort study was
      completed of patients with mucosal HNCA identified by International
      Classification of Disease, Ninth Revision (ICD-9) codes receiving consultation at
      the authors' institution from 2003 to 2008. Patients who received primary and
      adjuvant radiation at an academic center or in the community were included. The
      authors compared treatment completion rates and performed univariate and
      multivariate analyses of treatment outcomes. RESULTS: Of 388 patients, 210
      completed treatment at an academic center and 145 at a community center (33
      excluded, location unknown). Patients with HNCA undergoing radiation at an
      academic site had more advanced disease (P = .024) and were more likely to
      receive concurrent chemotherapy. Academic hospitals had a higher percentage of
      noncurrent smokers, higher median income, and higher percentage of oropharyngeal
      tumors. There was no significant difference in the rate of planned treatment
      completion between community and academic centers (93.7% vs 94.7%, P > .81) or
      rate of treatment breaks (22.4% vs 28.4%, P > .28). On Kaplan-Meier analysis, the
      5-year survival rate was 53.2% (95% confidence interval [CI], 45.3%-61.1%) for
      academic centers and 32.8% (95% CI, 22.0%-43.6%) for community hospitals (P <
      .001). CONCLUSION: In this cohort, although treatment completion and treatment
      breaks were similar between academic and community centers, survival rates were
      higher in patients treated in an academic setting.

PMID- 22875781
TI  - Ferritin as an independent mortality predictor in patients with pancreas cancer.
      Results of a pilot study.
AB  - Prognosis of patients with pancreas cancer is very poor. The aim of the study was
      to test the significance of laboratory parameters in the prognosis of patients
      with pancreas cancer. The studied group included 57 patients (31 men, 26 women,
      mean age 65 +/- 9 years). Blood was collected at the time of diagnosis of
      pancreas cancer and basic laboratory parameters, including nutritional and
      inflammatory markers and tumour markers were measured. Patients were followed up
      until death (median survival 147 days). Ferritin, iron, albumin, prealbumin,
      cholinesterase, haemoglobin, C-reactive protein, alkaline phosphatase and
      carcinoembryonic antigen were significant for patients' prognosis in univariate
      analysis while CA 19-9, bilirubin, liver, pancreas and kidney tests and lipids
      were not. Multivariate Cox regression demonstrated ferritin, iron and albumin as
      independent mortality predictors (RR (95%CI), per standard deviation: ferritin
      1.497(1.215-2.241), p = 0.002; albumin, 0.716(0.521-0.977), p = 0.035; iron,
      0.678(0.504-0.915), p = 0.010). Iron correlated significantly with albumin (r =
      0.397, p = 0.002) but neither iron nor albumin correlated with ferritin. Patients
      who survived 100 days had significantly lower ferritin (median 239 MUg/l vs. non
      survivors 435 MUg/l, p = 0.014), significantly higher albumin but the difference
      in serum iron was not quite significant. ROC analysis for ferritin revealed AUC
      for 100 days survival of 0.710, p = 0.007 (and 0.725, p = 0.004 for 200 days
      survival). AUC for albumin for 100 days survival was not significant (p = 0.073).
      This study points out ferritin as an independent mortality predictor in patients
      with pancreas cancer. High serum levels of ferritin at the time of diagnosis of
      pancreas cancer indicate bad prognosis of the patient.

PMID- 22875782
TI  - Does HE4 have a role as biomarker in the recurrence of ovarian cancer?
AB  - Human epididymis protein 4 (HE4) was recently approved by the Food and Drug
      Administration to monitor recurrence or progressive disease in epithelial ovarian
      cancer in conjunction with CA125. This is the first prospective controlled study
      in literature evaluating the sensitivity and specificity of HE4 and CA125 in
      detecting recurrent ovarian cancer. Serum samples were obtained 24 h before
      surgery from 34 patients with suspicious recurrent ovarian cancer and from 34
      patients with benign adnexal pathology, operated from November 2010 to November
      2011 at University Campus Bio-Medico of Rome. The CA125 normal value is
      considered less than 35 U/mL. Two HE4 cut-off are considered: less than 70 pmol/L
      and less than 150 pmol/L. The specificity analysis was performed using the
      parametric t test to compare the CA125 series and the Mann-Whitney test for the
      HE4 series. The level of statistical significance is set at p < 0.05. The CA125
      sensitivity and specificity in detecting recurrent ovarian cancer is 35.29 and
      58.82 %, respectively. The HE4 sensitivity is 73.53 and 26.47 %, for 70 pmol/L
      and 150 pmol/L cut-off, respectively. The HE4 specificity is 100 %. Combining
      CA125 and HE4 at cut-off of 70 pmol/L, the sensitivity to detect recurrent
      ovarian cancer is 76.47 % with a specificity of 100 %. The combination of CA125
      and HE4 at cut-off of 70 pmol/L improves the overall sensitivity and specificity
      of CA125 alone, suggesting a useful application of HE4 in strategies for
      surveillance of ovarian cancer recurrence.

PMID- 22875783
TI  - Effects of microvascular density on primary pulmonary non-Hodgkin's lymphoma
      (PPL).
AB  - This study aims to analyze 30 cases of primary pulmonary lymphoma (PPL) including
      treatment as well as follow-up information during the past 10 years and to
      investigate the correlation between microvessel density (MVD) and survival in
      patients with PPL. We reviewed all patients from October 2000 to October 2010.
      Patient demographics such as survival, recurrence, time to follow-up, and
      treatment mode were recorded. We also assessed MVD in the pretreated pulmonary
      lymphoma tissues of 30 previously untreated patients using alpha-CD34
      immunohistochemical staining. The median age of the 30 patients was 46.9 years.
      With a median follow-up of 4.3 years (range, 2 to 10 years), the 5-year overall
      survival (OS) rate was 57 % and progression-free survival (PFS) was 44 %. High
      MVD, elevated serum lactate dehydrogenase (LDH), and B symptoms was significantly
      correlated with clinical features and shorter PFS (P(MVD) = 0.021, P(LDH) =
      0.023, and P(B symptoms) = 0.005) and OS (P(MVD) = 0.028, P(LDH) = 0.032, and P(B
      symptoms) = 0.001). Application of surgical treatment improved the PFS (P =
      0.024) and OS(P = 0.028) of patients with stage IE disease (patients who were
      nodal negative). The patient's stage predicted the outcome and guides the use of
      treatments. Patients with high MVD measured in the microenvironment had worse
      PFS/OS than those with low MVD expression. Patients who had B symptoms or
      elevated serum LDH had poor prognosis. Patients with lymph node involvement
      (stage IIE or greater) had poor prognosis.

PMID- 22875784
TI  - P2X7 receptor activation induces inflammatory responses in salivary gland
      epithelium.
AB  - Inflammation of the salivary gland is a well-documented aspect of salivary gland
      dysfunction that occurs in Sjogren's syndrome (SS), an autoimmune disease, and in
      gamma-radiation-induced injury during treatment of head and neck cancers.
      Extracellular nucleotides have gained recognition as key modulators of
      inflammation through activation of cell surface ionotropic and metabotropic
      receptors, although the contribution of extracellular nucleotides to salivary
      gland inflammation is not well understood. In vitro studies using submandibular
      gland (SMG) cell aggregates isolated from wild-type C57BL/6 mice indicate that
      treatment with ATP or the high affinity P2X7R agonist 3'-O-(4-benzoyl)benzoyl-ATP
      (BzATP) induces membrane blebbing and enhances caspase activity, responses that
      were absent in SMG cell aggregates isolated from mice lacking the P2X7R (P2X7R(-/
      )). Additional studies with SMG cell aggregates indicate that activation of the
      P2X7R with ATP or BzATP stimulates the cleavage and release of alpha-fodrin, a
      cytoskeletal protein thought to act as an autoantigen in the development of SS.
      In vivo administration of BzATP to ligated SMG excretory ducts enhances immune
      cell infiltration into the gland and initiates apoptosis of salivary epithelial
      cells in wild-type, but not P2X7R(-/-), mice. These findings indicate that
      activation of the P2X7R contributes to salivary gland inflammation in vivo,
      suggesting that the P2X7R may represent a novel target for the treatment of
      salivary gland dysfunction.

PMID- 22875786
TI  - SDF-1alpha (CXCL12) regulation of lateral mobility contributes to activation of
      LFA-1 adhesion.
AB  - Regulation of integrin activity enables leukocytes to circulate freely, avoiding
      inappropriate adhesion while maintaining the ability to adhere quickly at sites
      of infection or inflammation. This regulation involves at least two components:
      affinity for ligand and affinity-independent avidity effects such as lateral
      mobility. Using lymphocyte function associated antigen-1 (LFA-1) as a model, we
      investigated the role of integrin release from cytoskeletal motion constraints in
      response to the chemokine stromal cell-derived factor-1 (SDF-1alpha) in this
      process. All experiments were done in primary T cells to avoid nonphysiological
      activation processes often seen with the use of cell lines. We found that SDF
      1alpha releases LFA-1 from cytoskeletal constraints as effectively as does
      cytochalasin D. The resultant increased diffusion is correlated with a robust
      increase in LFA-1-mediated adhesion under physiological shear stress. We further
      investigated the role of the highly conserved GFFKR sequence in the LFA-1
      cytoplasmic domain. We report that the GFFKR sequence is both necessary and
      sufficient for regulation of the SDF-1alpha-triggered proadhesive release from
      cytoskeleton interactions. While this does not address the role of transient SDF
      1alpha-induced conformational changes in the activation process, these results
      strongly suggest that any model of chemokine-induced LFA-1 activation must take
      into account chemokine-induced integrin lateral mobility. In addition, these
      results have ramifications for models of differential binding of LFA-1 to surface
      bound vs. soluble intercellular adhesion molecule-1.

PMID- 22875785
TI  - Angiotensin II stimulates superoxide production in the thick ascending limb by
      activating NOX4.
AB  - Angiotensin II (ANG II) stimulates production of superoxide (O(2)(-)) by NADPH
      oxidase (NOX) in medullary thick ascending limbs (TALs). There are three isoforms
      of the catalytic subunit (NOX1, 2, and 4) known to be expressed in the kidney. We
      hypothesized that NOX2 mediates ANG II-induced O(2)(-) production by TALs. To
      test this, we measured NOX1, 2, and 4 mRNA and protein by RT-PCR and Western blot
      in TAL suspensions from rats and found three catalytic subunits expressed in the
      TAL. We measured O(2)(-) production using a lucigenin-based assay. To assess the
      contribution of NOX2, we measured ANG II-induced O(2)(-) production in wild-type
      and NOX2 knockout mice (KO). ANG II increased O(2)(-) production by 346 relative
      light units (RLU)/mg protein in the wild-type mice (n = 9; P < 0.0007 vs.
      control). In the knockout mice, ANG II increased O(2)(-) production by 290 RLU/mg
      protein (n = 9; P < 0.007 vs. control). This suggests that NOX2 does not
      contribute to ANG II-induced O(2)(-) production (P < 0.6 WT vs. KO). To test
      whether NOX4 mediates the effect of ANG II, we selectively decreased NOX4
      expression in rats using an adenovirus that expresses NOX4 short hairpin (sh)RNA.
      Six to seven days after in vivo transduction of the kidney outer medulla, NOX4
      mRNA was reduced by 77%, while NOX1 and NOX2 mRNA was unaffected. In control
      TALs, ANG II stimulated O(2)(-) production by 96%. In TALs transduced with NOX4
      shRNA, ANG II-stimulated O(2)(-) production was not significantly different from
      the baseline. We concluded that NOX4 is the main catalytic isoform of NADPH
      oxidase that contributes to ANG II-stimulated O(2)(-) production by TALs.

PMID- 22875787
TI  - Regulation of the blood-testis barrier by coxsackievirus and adenovirus receptor.
AB  - The blood-testis barrier (BTB) divides the seminiferous epithelium into the basal
      and the adluminal compartment. It restricts paracellular diffusion of molecules
      between Sertoli cells, confers cell polarity, and creates a unique
      microenvironment in the adluminal compartment for spermatid development. However,
      it undergoes restructuring during the epithelial cycle so that preleptotene
      spermatocytes differentiated from type B spermatogonia residing in the basal
      compartment can traverse the BTB at stage VIII of the cycle, while the
      immunological barrier is maintained. Herein, coxsackievirus and adenovirus
      receptor (CAR), a tight junction (TJ) integral membrane protein in the testis and
      multiple epithelia and endothelia, was found to act as a regulatory protein at
      the BTB, besides serving as a structural adhesion protein. RNAi-mediated
      knockdown of CAR in a Sertoli cell epithelium with an established TJ-permeability
      barrier that mimicked the BTB in vivo resulted in a disruption of the TJ barrier
      and an increase in endocytosis of the TJ-protein occludin. Furthermore, such an
      enhancement in occludin endocytosis was accompanied by a downregulation of Thr
      phosphorylation in occludin and an increase in the association of endocytosed
      occludin with early endosome antigen-1. These findings were confirmed by
      overexpressing CAR in Sertoli cells, which was found to "tighten" the Sertoli
      cell TJ barrier, promoting BTB function. These findings support the emerging
      concept that CAR is not only a structural protein, it is involved in conferring
      the phosphorylation status of other adhesion proteins at the BTB (e.g., occludin)
      possibly mediated via its structural interactions with nonreceptor protein
      kinases, thereby modulating endocytic vesicle-mediated protein trafficking.

PMID- 22875788
TI  - Objective outcomes of extra-esophageal symptoms following laparoscopic total
      fundoplication by means of combined multichannel intraluminal impedance pH-metry
      before and after surgery.
AB  - Identifying and treating patients with extra-esophageal symptoms is a challenge.
      When the patient is unable to control his symptoms with pharmacological therapy
      alone, anti-reflux surgery may be indicated. This study aims to evaluate the
      outcomes of total fundoplication in the resolution of extra-esophageal
      manifestations and verify changes in 24-h MII-pH monitoring before and after
      surgery. From October 2005 to October 2010, patients who reported respiratory
      symptoms, possibly related to GERD, have been sent to our Institute. All patients
      were practiced ambulatory 24-h MII-pH before and after surgery. Thirty-five
      patients selected for the antireflux surgery have undergone all the same surgical
      procedures. Data were collected prospectively at 6 and 12 months after
      laparoscopic fundoplication. After laparoscopic fundoplication, the total
      percentage of exposure time with esophageal pH < 4, and both in upright and
      supine position was very low. A statistically significant difference (p < 0.05)
      was found in the number of detected refluxes at MII and detected refluxes at MII
      15-cm segment in pre and post-operative period. Symptom relief was obtained in
      all patients. Laparoscopic fundoplication is a safe and effective procedure to
      protect from refractory GERD and extra-esophageal symptoms, when evaluated with a
      thorough pre-operative selection.

PMID- 22875789
TI  - Motivated independence? Implicit party identity predicts political judgments
      among self-proclaimed Independents.
AB  - Reporting an Independent political identity does not guarantee the absence of
      partisanship. Independents demonstrated considerable variability in relative
      identification with Republicans versus Democrats as measured by an Implicit
      Association Test (IAT; M = 0.10, SD = 0.47). To test whether this variation
      predicted political judgment, participants read a newspaper article describing
      two competing welfare (Study 1) or special education (Study 2) policies. The
      authors manipulated which policy was proposed by which party. Among self
      proclaimed Independents, those who were implicitly Democratic preferred the
      liberal welfare plan, and those who were implicitly Republican preferred the
      conservative welfare plan. Regardless of the policy details, these implicit
      partisans preferred the policy proposed by "their" party, and this effect
      occurred more strongly for implicit than explicit plan preference. The authors
      suggest that implicitly partisan Independents may consciously override some
      partisan influence when making explicit political judgments, and Independents may
      identify as such to appear objective even when they are not.

PMID- 22875790
TI  - Second-look arthroscopic assessment of arthroscopic single-bundle posterior
      cruciate ligament reconstruction: comparison of mixed graft versus achilles
      tendon allograft.
AB  - BACKGROUND: Although controversy continues over the choice of graft tissue,
      including autografts, allografts, and synthetic ligaments, for posterior cruciate
      ligament (PCL) reconstruction, the use of a mixed graft consisting of a hamstring
      (semitendinosus and gracilis) autograft plus tibialis anterior allograft tendon
      has not been studied in detail. HYPOTHESIS: Outcomes of PCL reconstructions
      performed with a mixed graft would be superior to those using solely an Achilles
      tendon allograft in terms of functional knee scores, posterior stability, and the
      graft appearance. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      Fifty-eight patients who underwent isolated single-bundle PCL reconstruction
      using an arthroscopic trans-septal portal with remnant preservation technique
      were evaluated. They were divided into group A (mixed tendon; n = 30) and group B
      (Achilles tendon; n = 28). Knee function was evaluated using the Lysholm knee
      score, Tegner activity score, and the International Knee Documentation Committee
      (IKDC) grading scale. Anteroposterior stability was measured using the Telos
      stress view. Twenty patients (66.7%) from group A and 21 patients (75.0%) from
      group B underwent hardware removal and a second-look arthroscopic examination.
      RESULTS: The Lysholm knee scores in groups A and B increased from a respective
      average of 43 and 50 preoperatively to 90 and 88 at follow-up. The IKDC grade and
      Tegner activity scores were also significantly improved in both groups. Stability
      was improved in both groups, with an average posterior laxity of 3.0 mm (group A)
      and 3.3 mm (group B) at follow-up (P > .05). However, there were 4 intraoperative
      complications in group B: 2 bone fractures and 2 graft pullouts during precyclic
      tensioning. Second-look arthroscopy revealed a partial tear in 8 cases (40%) from
      group A and 15 cases (71.4%) from group B (P = .03). All of the partial tears
      were located in the femoral aperture area. Complete synovial coverage was
      demonstrated in 10 patients (50%) from group A and 5 patients (23.8%) from group
      B (P = .04). However, clinical outcomes and stability were not affected by the
      arthroscopic graft appearance. CONCLUSION: Satisfactory results were obtained for
      groups A and B in patients who underwent reconstruction for isolated PCL injury.
      However, 4 intraoperative complications (14.3%) were encountered with use of the
      Achilles tendon allograft (group B), with a relative higher rate of partial tear
      and less synovialization in the femoral aperture area.

PMID- 22875791
TI  - Electromyography and nerve conduction velocity for the evaluation of the
      infraspinatus muscle and the suprascapular nerve in professional beach volleyball
      players.
AB  - BACKGROUND: Beach volleyball is an overhead sport with a high prevalence of
      infraspinatus muscle atrophy of the hitting shoulder. HYPOTHESIS: Infraspinatus
      muscle atrophy seems to be caused by a repetitive traction injury of the
      suprascapular nerve. Early pathological findings might be assessed with surface
      electromyography (EMG) and nerve conduction velocity (NCV) measurements. STUDY
      DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Fully competitive
      professional beach volleyball players were assessed with a structured interview,
      shoulder examination, strength measurements (external rotation and elevation),
      and neurophysiological examination (surface EMG and NCV of the infraspinatus and
      supraspinatus muscles and the suprascapular nerve, respectively) during the Beach
      Volleyball Grand Slam tournament 2010 in Klagenfurt, Austria. RESULTS: Thirty
      five men with an average age of 28 years were examined. Visible infraspinatus
      atrophy was found in 12 players (34%), of which 8 (23%) had slight atrophy and 4
      (11%) had severe atrophy. External rotation (90%; P < .006) and elevation
      strength (93%; P = .03) were significantly lower in the hitting shoulder.
      Electromyography revealed a higher activation pattern in the infraspinatus muscle
      of the hitting arm in players with no or slight atrophy (P = .001) but a
      significantly lower activation pattern in players with severe atrophy (P = .013).
      Nerve conduction velocity measurements showed a significant higher latency and
      lower amplitude in the hitting shoulder of the total study group and the subgroup
      with infraspinatus atrophy. CONCLUSION: Professional beach volleyball players
      have a high frequency of infraspinatus atrophy (34%) and significantly reduced
      shoulder strength of the hitting shoulder. These findings are not associated with
      demographic factors. Electromyography and NCV measurements suggest a
      suprascapular nerve involvement caused by repetitive strain injuries of the
      nerve. External rotation strength measurements and NCV measurements can detect a
      side-to-side difference early, while EMG may show compensation mechanisms for
      progressive damaging of the suprascapular nerve and, as a result, loss of
      infraspinatus muscle strength.

PMID- 22875792
TI  - Arthroscopic accessibility of the talus quantified by computed tomography
      simulation.
AB  - BACKGROUND: Anterior ankle arthroscopy is the preferred surgical approach for the
      treatment of osteochondral defects of the talus (OCDs). However, the ankle is a
      congruent joint with limited surgical access. PURPOSE: The dual purpose of this
      study was (1) to quantify the anterior arthroscopic reach (defined as the
      proportion of the talar dome articular surface located anterior to the anterior
      distal tibial rim) with the ankle in full plantar flexion and (2) to identify
      predictive factors of the arthroscopic reach. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Computed tomography scans were obtained of 59 ankles
      (57 patients aged 33 +/- 11 years) in full plantar flexion in a nonmetallic 3
      dimensional footplate. The arthroscopic reach of both the medial and lateral
      talar domes was assessed on sagittal reconstructions using a custom-made software
      routine. Intraobserver and interobserver reliability were calculated by
      intraclass correlation coefficients (ICCs). Various predictive factors of the
      arthroscopic reach were analyzed by multivariate linear regression analysis.
      RESULTS: The arthroscopic reach was 48.2% +/- 6.7% (range, 26.7%-60.7%) of the
      medial talar dome and 47.8% +/- 6.5% (range, 31.2%-65.1%) of the lateral talar
      dome (P = .62). The intraobserver and interobserver reliability of both
      measurements were excellent (ICC, .99). The clinical plantarflexion angle was a
      statistically significant predictive factor of both the medial and lateral
      arthroscopic reaches (ie, increased plantar flexion corresponded to increased
      area of access), while joint laxity, gender, and age were not predictive.
      CONCLUSION: Almost half of the talar dome is accessible anterior to the anterior
      distal tibial rim. The plantarflexion angle is an independent predictive factor
      of the arthroscopic reach both medially and laterally. CLINICAL RELEVANCE: These
      results may facilitate preoperative planning of the surgical approach for OCDs.

PMID- 22875793
TI  - Medical forensic examination of detained immigrants: is the Istanbul Protocol
      followed?
AB  - INTRODUCTION: Maltreatment and torture during custody is still an important
      problem in many countries. Both national and international regulations and the
      Istanbul Protocol are of great importance in terms of elimination of maltreatment
      and torture. In this study, we evaluated whether examinations for custody of
      immigrants were performed in accordance with the Istanbul Protocol. METHOD: We
      retrospectively evaluated reports of forensic examinations for custody of 100
      immigrants in Van-Caldiran Government Hospital in 2009. Data about nationality,
      age, gender, examination date, referring department, examination findings and
      departments to which the reports were submitted were collected. RESULTS: Fifty
      percent of the immigrants were Iranian and they were aged between 11 and 62
      years. Ninety-nine immigrants were men and one was woman. Data about history of
      arrest were missing in forensic reports about all immigrants. Data about signs of
      trauma were present only for seven immigrants. Ninety-three immigrants were
      reported to have no signs of trauma. None of the immigrants underwent psychiatric
      examination. All forensic reports were found to be submitted to the police
      personally. Whether the immigrants were examined before or after the custody was
      not clear in the reports. CONCLUSION: Evaluation of the data showed that none of
      the forensic examinations were performed in accordance with the Istanbul
      Protocol. It can be recommended that the protocol should be incorporated into the
      curricula for undergraduate, graduate and in-service training programmes in order
      to improve relevant forensic practices.

PMID- 22875794
TI  - Evaluating the performance of whole genome amplification for use in low template
      DNA typing.
AB  - We report on the performance of two whole genome amplification methods,
      GenomiPhiTM amplification and modified-improved primer extension preamplification
      (mIPEP), when analysing low template DNA samples. Template as low as 10 pg
      treated with mIPEP generated more than 1 ng of DNA that could be used in STR
      typing. Initial templates of 100-10 pg, when treated with mIPEP, generated an
      increase in alleles compared with control samples. Partial profiles using the
      AmpFlSTR((r)) IdentifilerTM Kit were produced from this suboptimal DNA template,
      with 70% of the possible alleles (21.7 +/- 2.1 in 32 alleles) recorded, using the
      mIPEP amplified products with an initial template of 100 pg. Allelic imbalance
      decreased with samples treated with whole genome amplification method (WGA)
      compared with those without this initial treatment. Further methods for
      improvement were also analysed including altering the condition of electrokinetic
      injection, and the successful DNA typing rate was increased to about 80%. This
      report illustrates the potential use and limitations of WGA for low template
      samples.

PMID- 22875795
TI  - Homicide-suicide events in Southwestern Croatia, 1986-2009.
AB  - The aim of this study was to investigate the occurrence and characteristics of
      homicide-suicide events in Southwestern Croatia from 1986-2009 relying on autopsy
      reports of the Department of Forensic Medicine and Criminalistics, Rijeka and
      police records. A total of 17 cases involving 19 victims were identified. The
      perpetrators were most often men (82%), living in a spousal relationship with the
      victim. In 76.5% cases, suicide was committed immediately after homicide, and the
      same mean (most often an illegal firearm) was used for both. After examining the
      belongings of those involved in homicide-suicides, two factors differentiated our
      study from others, i.e. more victims and perpetrators were from the lower
      socioeconomic class and explosives were used in two homicide-suicide (12%) cases.
      The greater frequency of explosive used in homicide-suicide events may be a
      result of factors associated with the recent war fought in Croatia. These data
      prove the influence of sociological, historical and also political factors on the
      characteristics of a rare event such as homicide-suicide.

PMID- 22875796
TI  - USPIO-enhanced MR angiography of arteriovenous fistulas in patients with renal
      failure.
AB  - PURPOSE: To determine the feasibility of using ferumoxytol-enhanced magnetic
      resonance (MR) angiography to depict the vasculature of hemodialysis fistulas and
      improve image quality compared with nonenhanced time-of-flight (TOF) MR
      angiography. MATERIALS AND METHODS: The study was institutional review board
      approved and was in compliance with HIPAA regulations. All participants provided
      written informed consent. TOF and first-pass ferumoxytol-enhanced MR angiography
      were performed in 10 patients with upper extremity autogenous fistulas.
      Ferumoxytol was administered as a bolus solution containing 430 MUmol of
      elemental iron. A qualitative comparison was performed on maximum intensity
      projection images. Lumen depiction was evaluated by using a five-point scale. The
      uniformity of intraluminal signal intensity was measured as the ratio between the
      mean signal intensity of the entirety of the imaged fistula and its standard
      deviation. The contrast-to-noise ratio (CNR) between intraluminal signal and
      adjacent tissue was evaluated as a function of image acquisition time. Lumen
      depiction scores, luminal signal heterogeneity, and CNR efficiency were compared
      between TOF and ferumoxytol-enhanced MR angiography by using a Wilcoxon-Mann
      Whitney test. RESULTS: Flow artifacts were greatly reduced by the use of
      ferumoxytol-enhanced MR angiography. Ferumoxytol-enhanced MR angiography had
      significantly better performance than TOF MR angiography as measured with the
      following: lumen depiction scores in all segments (mean, 4.7+/-0.1 [standard
      error of the mean]; vs 3.0+/-0.3 for arterial inflow, 4.1+/-0.3 vs 1.9+/-0.3 for
      arterial outflow, 3.7+/-0.3 vs 1.8+/-0.2 for anastomosis, and 4.5+/-0.2 vs 2.1+/
      0.2 for venous outflow; P<.001), intraluminal signal homogeneity (0.3+/-0.02 vs
      0.4+/-0.06, P=.005), and CNR efficiency in the venous outflow (5.1+/-0.6 vs 2.5+/
      0.4, P=.01). CONCLUSION: This study demonstrates the feasibility of using
      ferumoxytol-enhanced MR angiography in imaging hemodialysis fistulas with
      consistently superior image quality compared with nonenhanced TOF MR angiography.

PMID- 22875797
TI  - Hippocampal calcification prevalence at CT: a retrospective review.
AB  - PURPOSE: To determine the prevalence of intrahippocampal calcification at brain
      computed tomography (CT), evaluate any association with calcification involving
      the intracranial arteries or lentiform nuclei, and assess the clinical importance
      of intrahippocampal calcification. MATERIALS AND METHODS: Study approval was
      obtained by the Southern Health Human Research Ethics Committee, which waived the
      requirement for informed consent because of the retrospective nature of the
      study. The presence of intrahippocampal calcification was assessed by four
      readers through retrospective review of 300 randomly selected nonenhanced brain
      CT scans. In addition, the presence of calcification involving the intracranial
      arteries and lentiform nuclei was assessed, and the clinical histories were
      reviewed in those patients with intrahippocampal calcifications and a matched
      control cohort without intrahippocampal calcification. Differences in proportion
      of patients with intrahippocampal calcifications across different age groups were
      assessed by using chi2 analysis. Interrater agreement and intrarater agreement
      were assessed by using kappa analysis. RESULTS: Intrahippocampal calcification
      was demonstrated in 47 (15.7%) of 300 patients, and 47 (21.7%) of 217 patients
      older than 50 years of age. Its prevalence increased with age (P=.008). All
      patients with intrahippocampal calcification and the control cohort demonstrated
      calcification involving the intracranial arteries. Eleven (23.4%) of 47 patients
      with intrahippocampal calcification had calcification within the lentiform nuclei
      compared with 14 (29.8%) of 47 in the control cohort (P=.67). The anatomic
      distribution of intrahippocampal calcification was similar to that described in
      vascular fibrosis and calcification. CONCLUSION: The prevalence of
      intrahippocampal calcification appears to increase with age and is a relatively
      common finding in patients older than 50 years. It has a similar anatomic
      distribution to microscopic vascular fibrosis and calcification and likely
      reflects its latter stages.

PMID- 22875798
TI  - Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986
      2005.
AB  - PURPOSE: To examine the incidence of clinically important cataracts in relation
      to lens radiation doses between 0 and approximately 3 Gy to address risks at
      relatively low brief doses. MATERIALS AND METHODS: Informed consent was obtained,
      and human subjects procedures were approved by the ethical committee at the
      Radiation Effects Research Foundation. Cataract surgery incidence was documented
      for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for
      cataract, such as smoking, hypertension, and corticosteroid use, were not
      confounders of the radiation effect on the basis of Cox regression analysis.
      Radiation dose-response analyses were performed for cataract surgery incidence by
      using Poisson regression analysis, adjusting for demographic variables and
      diabetes mellitus, and results were expressed as the excess relative risk (ERR)
      and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies
      [ERR] or adds to [EAR] the risk in the unexposed group). RESULTS: Of 6066 atomic
      bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The
      estimated threshold dose was 0.50 Gy (95% confidence interval [CI]: 0.10 Gy, 0.95
      Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A
      linear-quadratic test for upward curvature did not show a significant quadratic
      effect for either the ERR or EAR model. The linear ERR model for a 70-year-old
      individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53)
      [corrected] excess risk at 1 Gy. The ERR was highest for those who were young at
      exposure. CONCLUSION: These data indicate a radiation effect for vision-impairing
      cataracts at doses less than 1 Gy. The evidence suggests that dose standards for
      protection of the eye from brief radiation exposures should be 0.5 Gy or less.

PMID- 22875799
TI  - Coronary CT angiography versus conventional cardiac angiography for therapeutic
      decision making in patients with high likelihood of coronary artery disease.
AB  - PURPOSE: To assess the efficacy of coronary computed tomographic (CT) angiography
      for therapeutic decision making in patients with high likelihood of coronary
      artery disease (CAD)-specifically the ability of coronary CT angiography to help
      differentiate patients without and patients with a need for revascularization and
      determine the appropriate revascularization procedure. MATERIALS AND METHODS: The
      study protocol was approved by institutional review board, with written informed
      consent from all patients. The study was conducted in compliance with HIPAA. One
      hundred eighty-five consecutive symptomatic patients (121 men; mean age, 59.4
      years+/-9.7) with a positive single photon emission computed tomography (SPECT)
      myocardial perfusion study underwent coronary CT angiography and conventional
      cardiac angiography (hereafter, cardiac catheterization). The management strategy
      (conservative treatment vs revascularization) and revascularization procedure
      (percutaneous coronary intervention [PCI] vs coronary artery bypass graft surgery
      [CABG]) were prospectively selected on the basis of a combination of coronary CT
      angiography and SPECT. In addition, the authors calculated the accuracy,
      sensitivity, specificity, and negative and positive predictive values of coronary
      CT angiography in the detection of obstructive CAD and the selection of a
      revascularization strategy. Cardiac catheterization was used as the standard of
      reference. RESULTS: Of the 185 patients, 113 (61%) did not undergo
      revascularization and 42 (23%) were free of CAD. In 178 patients (96%), the same
      therapeutic strategy (conservative treatment vs revascularization) was chosen on
      the basis of coronary CT angiography and catheterization. All patients in need of
      revascularization were identified with coronary CT angiography. When
      revascularization was indicated, the same procedure (PCI vs CABG) was chosen in
      66 of 72 patients (92%). CONCLUSION: In patients with high likelihood of CAD, the
      performance of coronary CT angiography in the differentiation of patients without
      and patients with a need for revascularization and the selection of a
      revascularization strategy was similar to that of cardiac catheterization;
      accordingly, coronary CT angiography has the potential to limit the number of
      patients without obstructive CAD who undergo cardiac catheterization and to
      inform decision making regarding revascularization.

PMID- 22875801
TI  - Novel humanized and highly efficient bispecific antibodies mediate killing of
      prostate stem cell antigen-expressing tumor cells by CD8+ and CD4+ T cells.
AB  - Prostate cancer is the most common noncutaneous malignancy in men. The prostate
      stem cell Ag (PSCA) is a promising target for immunotherapy of advanced disease.
      Based on a novel mAb directed to PSCA, we established and compared a series of
      murine and humanized anti-CD3-anti-PSCA single-chain bispecific Abs. Their
      capability to redirect T cells for killing of tumor cells was analyzed. During
      these studies, we identified a novel bispecific humanized Ab that efficiently
      retargets T cells to tumor cells in a strictly Ag-dependent manner and at
      femtomolar concentrations. T cell activation, cytokine release, and lysis of
      target cells depend on a cross-linkage of redirected T cells with tumor cells,
      whereas binding of the anti-CD3 domain alone does not lead to an activation or
      cytokine release. Interestingly, both CD8+ and CD4+ T cells are activated in
      parallel and can efficiently mediate the lysis of tumor cells. However, the onset
      of killing via CD4+ T cells is delayed. Furthermore, redirecting T cells via the
      novel humanized bispecific Abs results in a delay of tumor growth in xenografted
      nude mice.

PMID- 22875800
TI  - Expansion of effector memory regulatory T cells represents a novel prognostic
      factor in lower risk myelodysplastic syndrome.
AB  - Myelodysplastic syndromes are premalignant diseases characterized by cytopenias,
      myeloid dysplasia, immune dysregulation with association to autoimmunity, and
      variable risk for acute myeloid leukemia transformation. Studies of FOXP3(+)
      regulatory T cells (Tregs) indicate that the number and/or activation state may
      influence cancer progression in these patients. Focusing on patients with a lower
      risk for leukemia transformation, 18 (34.6%) of 52 patients studied displayed an
      altered Treg compartment compared with age-matched controls. Delineation of
      unique Treg subsets revealed that an increase in the absolute number of
      CD4(+)FOXP3(+)CD25(+)CD127(low)CD45RA(-)CD27(-) Tregs (effector memory Tregs
      [Treg(EM)]) was significantly associated with anemia (p = 0.046), reduced
      hemoglobin (p = 0.038), and blast counts >=5% (p = 0.006). In healthy donors,
      this Treg(EM) population constitutes only 2% of all Tregs (one to six Tregs per
      microliter) in peripheral blood but, when isolated, exhibit greater suppressive
      activity in vitro. With a median follow-up of 3.1 y (range 2.7-4.9 y) from sample
      acquisition, increased numbers of Treg(EM) cells proved to have independent
      prognostic importance in survival estimates, suggesting that enumeration of this
      Treg subset may be a more reliable indicator of immunological escape than
      FOXP3(+) T cells as a whole. Based on multivariate analyses, Treg(EM) impacted
      survival independently from myeloblast characteristics, cytopenias, karyotype,
      and comorbidities. Based on these findings, Treg(EM) cell expansion may be
      synonymous with human Treg activation and indicate microenvironmental changes
      conducive to transformation in myelodysplastic syndromes.

PMID- 22875802
TI  - Globosides but not isoglobosides can impact the development of invariant NKT
      cells and their interaction with dendritic cells.
AB  - Recognition of endogenous lipid Ag(s) on CD1d is required for the development of
      invariant NKT (iNKT) cells. Isoglobotrihexosylceramide (iGb3) has been implicated
      as this endogenous selecting ligand and recently suggested to control
      overstimulation and deletion of iNKT cells in alpha-galactosidase A-deficient
      (alphaGalA(-/-)) mice (human Fabry disease), which accumulate isoglobosides and
      globosides. However, the presence and function of iGb3 in murine thymus remained
      controversial. In this study, we generate a globotrihexosylceramide (Gb3)
      synthase-deficient (Gb3S(-/-)) mouse and show that in thymi of alphaGalA(-/
      )/Gb3S(-/-) double-knockout mice, which store isoglobosides but no globosides,
      minute amounts of iGb3 can be detected by HPLC. Furthermore, we demonstrate that
      iGb3 deficiency does not only fail to impact selection of iNKT cells, in terms of
      frequency and absolute numbers, but also does not alter the distribution of the
      TCR CDR 3 of iNKT cells. Analyzing multiple gene-targeted mouse strains, we
      demonstrate that globoside, rather than iGb3, storage is the major cause for
      reduced iNKT cell frequencies and defective Ag presentation in alphaGalA(-/-)
      mice. Finally, we show that correction of globoside storage in alphaGalA(-/-)
      mice by crossing them with Gb3S(-/-) normalizes iNKT cell frequencies and
      dendritic cell (DC) function. We conclude that, although detectable in murine
      thymus in alphaGalA(-/-)/Gb3S(-/-) mice, iGb3 does not influence either the
      development of iNKT cells or their interaction with peripheral DCs. Moreover, in
      alphaGalA(-/-) mice, it is the Gb3 storage that is responsible for the decreased
      iNKT cell numbers and impeded Ag presentation on DCs.

PMID- 22875803
TI  - Host factor transcriptional regulation contributes to preferential expression of
      HIV type 1 in IL-4-producing CD4 T cells.
AB  - HIV type 1 (HIV-1) replicates preferentially in IL-4-producing CD4 T cells for
      unclear reasons. We show increased HIV-1 expression is irrespective of viral
      tropism for chemokine receptors as previously suggested, but rather transcription
      of the HIV-1 long terminal repeat (LTR) is increased in IL-4-producing CD4 T
      cells. Increased expression of HIV-1 message is also confirmed in IL-4-producing
      CD4 T cells from HIV-1-infected individuals ex vivo. In exploring a
      transcriptional mechanism, we identify a novel c-maf (required for IL-4
      expression) transcription factor binding site just upstream of the dual NF
      kappaB/NFAT binding sites in the proximal HIV-1 LTR. We demonstrate that c-maf
      binds this site in vivo and synergistically augments HIV-1 transcription in
      cooperation with NFAT2 and NF-kappaB p65, but not NFAT1 or NF-kappaB p50.
      Conversely, small interfering RNA inhibition of c-maf reduces HIV-1 transcription
      in IL-4-producing T cells. Thus, c-maf increases HIV-1 expression in IL-4
      producing CD4 T cells by binding the proximal HIV-1 LTR and augmenting HIV-1
      transcription in partnership with NFAT2 and NF-kappaB p65 specifically. This has
      important implications for selective targeting of transcription factors during
      HIV-1 infection because, over the course of HIV-1 progression/AIDS, IL-4
      producing T cells frequently predominate and substantially contribute to disease
      pathology.

PMID- 22875804
TI  - Enhanced Tim3 activity improves survival after influenza infection.
AB  - Influenza is a major cause of morbidity and mortality in the United States.
      Studies have shown that excessive T cell activity can mediate pneumonitis in the
      setting of influenza infection, and data from the 2009 H1N1 pandemic indicate
      that critical illness and respiratory failure postinfection were associated with
      greater infiltration of the lungs with CD8+ T cells. T cell Ig and mucin domain 3
      (Tim3) is a negative regulator of Th1/Tc1-type immune responses. Activation of
      Tim3 on effector T cells has been shown to downregulate proliferation, cell
      mediated cytotoxicity, and IFN-gamma production, as well as induce apoptosis. In
      this article, we demonstrate that deletion of the terminal cytoplasmic domain of
      the Tim3 gene potentiates its ability to downregulate Tc1 inflammation, and that
      this enhanced Tim3 activity is associated with decreased phosphorylation of the
      TCR-CD3zeta-chain. We then show that mice with this Tim3 mutation infected with
      influenza are protected from morbidity and mortality without impairment in viral
      clearance or functional heterotypic immunity. This protection is associated with
      decreased CD8+ T cell proliferation and decreased production of inflammatory
      cytokines, including IFN-gamma. Furthermore, the Tim3 mutation was protective
      against mortality in a CD8+ T cell-specific model of pneumonitis. These data
      suggest that Tim3 could be targeted to prevent immunopathology during influenza
      infection and demonstrate a potentially novel signaling mechanism used by Tim3 to
      downregulate the Tc1 response.

PMID- 22875805
TI  - Cutting edge: generation of memory precursors and functional memory CD8+ T cells
      depends on T cell factor-1 and lymphoid enhancer-binding factor-1.
AB  - T cell factor (TCF)-1 and lymphoid enhancer-binding factor (LEF)-1 transcription
      factors have redundant roles in promoting thymocyte maturation. TCF-1 has been
      recently shown to critically regulate memory CD8+ T cell differentiation and
      persistence. The complete spectra of regulatory roles for TCF-1 and LEF-1 in CD8+
      T cell responses are yet unknown. We conditionally targeted LEF-1, and by
      combination with germline deletion of TCF-1, we found that loss of both factors
      completely abrogated the generation of KLR G1(lo)IL-7Ralpha+ memory precursors in
      effector CD8+ T cell populations in response to Listeria monocytogenes infection.
      Whereas CD8+ effectors deficient for TCF-1 and LEF-1 retained the capacity to
      express IFN-gamma, granzyme B, and perforin, they were defective in TNF-alpha
      production. In the memory phase, the Ag-specific CD8+ T cells lacking TCF-1 and
      LEF-1 exhibited an effector phenotype and were severely impaired in secondary
      expansion upon rechallenge. Thus, TCF-1 and LEF-1 cooperatively regulate
      generation of memory precursors and protective memory CD8+ T cells.

PMID- 22875806
TI  - Successful treatment of Strongyloides stercoralis hyperinfection in a case of
      systemic lupus erythematosus - review of the literature regarding various
      treatment schedules.
AB  - Strongyloides stercoralis hyperinfection poses a great challenge to physicians in
      the tropics due to their non-specific symptoms and signs. Early identification
      and initiation of treatment improves mortality rates. Reports of Strongyloides
      infection in Hansens disease, systemic lupus erythematosus (SLE), organ
      transplant recipients and malnourished individuals have been reported in the
      published literature. The outcomes were variable, which may be attributed to a
      lack of treatment protocol. Treatment has been individualized and reports
      available are based on individual case reports and small case series. We report a
      successfully treated case of hyperinfection in SLE and discuss the various
      treatment options available.

PMID- 22875807
TI  - The cause of endomyocardial fibrosis in Uganda.
AB  - The cause of endomyocardial fibrosis in Uganda remains unknown in spite of
      studies dating back to 1948. Herbal decoctions have been used by traditional
      healers for countless generations to treat many complaints, especially fever. We
      present evidence - ethnic, geographical, tribal, pathological and distribution by
      age - that the toxic herbal decoctions taken as medicines in Uganda can cause
      endomyocardial fibrosis.

PMID- 22875808
TI  - MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social
      amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs.
AB  - The RNA interference machinery has served as a guardian of eukaryotic genomes
      since the divergence from prokaryotes. Although the basic components have a
      shared origin, silencing pathways directed by small RNAs have evolved in diverse
      directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein
      coding genes and play vital roles in plants and animals, but less is known about
      their functions in other organisms. Here, we report, for the first time, deep
      sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA
      from growing single-cell amoebae as well as from two multicellular developmental
      stages was sequenced. Computational analyses combined with experimental data
      reveal the expression of miRNAs, several of them exhibiting distinct expression
      patterns during development. To our knowledge, this is the first report of miRNAs
      in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors
      generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is
      dependent on the Dicer-like protein DrnB, further supporting the presence of
      miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin
      structures originating from an intron as well as from a class of repetitive
      elements. We believe that these repetitive elements are sources for newly evolved
      miRNAs.

PMID- 22875810
TI  - Photosynthetic thermotolerance of woody savanna species in China is correlated
      with leaf life span.
AB  - BACKGROUND AND AIMS: Photosynthetic thermotolerance (PT) is important for plant
      survival in tropical and sub-tropical savannas. However, little is known about
      thermotolerance of tropical and sub-tropical wild plants and its association with
      leaf phenology and persistence. Longer-lived leaves of savanna plants may
      experience a higher risk of heat stress. Foliar Ca is related to cell integrity
      of leaves under stresses. In this study it is hypothesized that (1) species with
      leaf flushing in the hot-dry season have greater PT than those with leaf flushing
      in the rainy season; and (2) PT correlates positively with leaf life span, leaf
      mass per unit area (LMA) and foliar Ca concentration ([Ca]) across woody savanna
      species. METHODS: The temperature-dependent increase in minimum fluorescence was
      measured to assess PT, together with leaf dynamics, LMA and [Ca] for a total of
      24 woody species differing in leaf flushing time in a valley-type savanna in
      south-west China. KEY RESULTS: The PT of the woody savanna species with leaf
      flushing in the hot-dry season was greater than that of those with leaf flushing
      in the rainy season. Thermotolerance was positively associated with leaf life
      span and [Ca] for all species irrespective of the time of flushing. The
      associations of PT with leaf life span and [Ca] were evolutionarily correlated.
      Thermotolerance was, however, independent of LMA. CONCLUSIONS: Chinese savanna
      woody species are adapted to hot-dry habitats. However, the current maximum leaf
      temperature during extreme heat stress (44.3  degrees C) is close to the critical
      temperature of photosystem II (45.2  degrees C); future global warming may
      increase the risk of heat damage to the photosynthetic apparatus of Chinese
      savanna species.

PMID- 22875811
TI  - The cost of myrmecophytism: insights from allometry of stem secondary growth.
AB  - BACKGROUND AND AIMS: Plant defence traits against herbivores incur production
      costs that are usually difficult to measure. However, estimating these costs is a
      prerequisite for characterizing the plant defence strategy as a whole.
      Myrmecophytes are plants that provide symbiotic ants with specialized nesting
      cavities, called domatia, in exchange for protection against herbivores. In the
      particular case of stem domatia, production of extra wood seems to be the only
      associated cost, making this indirect defence trait a particularly suitable model
      for estimating the cost of defence. METHODS: Measurements were made of growth
      pattern and cumulative production cost of domatia over secondary growth in the
      myrmecophyte Leonardoxa africana subsp. africana, whose internodes display both a
      solid basal segment and a hollow distal part (the domatium), thus allowing paired
      comparison of investment in wood. KEY RESULTS: Previous studies showed that
      'overconstruction' of the hollow part of internodes during primary growth is
      needed for mechanical support. In this study, it is shown that the relationship
      between the woody cross-sectional area of the solid and hollow parts of
      internodes is negatively allometric at the beginning of secondary growth and
      nearly isometric later on. Thus, in hollow stems, the first phase of slow
      secondary growth compensates for the 'overconstruction' of the ring of wood
      during primary growth. Moreover, the cumulative production cost of a domatium
      (estimated as the additional volume of wood required for a hollow stem compared
      with a solid one) is very high at the beginning of secondary growth and then
      quickly tends to zero. CONCLUSIONS: Making domatia incurs high costs early in
      ontogeny, costs that are then amortized later in development of stems and of
      individual plants. Characterizing ontogenetic variation of the net cost of this
      peculiar defence mechanism will help us build more accurate theoretical models of
      resource allocation in myrmecophytes.

PMID- 22875809
TI  - Biogenesis of telomerase ribonucleoproteins.
AB  - Telomerase adds simple-sequence repeats to the ends of linear chromosomes to
      counteract the loss of end sequence inherent in conventional DNA replication.
      Catalytic activity for repeat synthesis results from the cooperation of the
      telomerase reverse transcriptase protein (TERT) and the template-containing
      telomerase RNA (TER). TERs vary widely in sequence and structure but share a set
      of motifs required for TERT binding and catalytic activity. Species-specific TER
      motifs play essential roles in RNP biogenesis, stability, trafficking, and
      regulation. Remarkably, the biogenesis pathways that generate mature TER differ
      across eukaryotes. Furthermore, the cellular processes that direct the assembly
      of a biologically functional telomerase holoenzyme and its engagement with
      telomeres are evolutionarily varied and regulated. This review highlights the
      diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere
      recruitment among ciliates, yeasts, and vertebrates and suggests common themes in
      these pathways and their regulation.

PMID- 22875812
TI  - The impact of dehydration rate on the production and cellular location of
      reactive oxygen species in an aquatic moss.
AB  - BACKGROUND AND AIMS: The aquatic moss Fontinalis antipyretica requires a slow
      rate of dehydration to survive a desiccation event. The present work examined
      whether differences in the dehydration rate resulted in corresponding differences
      in the production of reactive oxygen species (ROS) and therefore in the amount of
      cell damage. METHODS: Intracellular ROS production by the aquatic moss was
      assessed with confocal laser microscopy and the ROS-specific chemical probe 2,7
      dichlorodihydrofluorescein diacetate. The production of hydrogen peroxide was
      also quantified and its cellular location was assessed. KEY RESULTS: The
      rehydration of slowly dried cells was associated with lower ROS production,
      thereby reducing the amount of cellular damage and increasing cell survival. A
      high oxygen consumption burst accompanied the initial stages of rehydration,
      perhaps due to the burst of ROS production. CONCLUSIONS: A slow dehydration rate
      may induce cell protection mechanisms that serve to limit ROS production and
      reduce the oxidative burst, decreasing the number of damaged and dead cells due
      upon rehydration.

PMID- 22875813
TI  - Up and down: stamen movements in Ruta graveolens (Rutaceae) enhance both
      outcrossing and delayed selfing.
AB  - BACKGROUND AND AIMS: Stamen movements directly determine pollen fates and mating
      patterns by altering positions of female and male organs. However, the
      implications of such movements in terms of pollination are not well understood.
      Recently, complex patterns of stamen movements have been identified in Loasaceae,
      Parnassiaceae, Rutaceae and Tropaeolaceae. In this study the stamen movements in
      Ruta graveolens (Rutaceae) and their impact on pollination are determined.
      METHODS: Pollination effects of stamen movements were studied in Ruta graveolens,
      in which one-by-one uplifting and falling back is followed by simultaneous
      movement of all stamens in some flowers. Using 30 flowers, one stamen was
      manipulated either to be immobilized or to be allowed to move freely towards the
      centre of the flower but be prevented from falling back. Pollen loads on stigmas
      and ovule fertilization in flowers with or without simultaneous stamen movement
      were determined. RESULTS: Pollen removal decreased dramatically (P < 0.001) when
      the stamen was stopped from uplifting because its anther was seldom contacted by
      pollinators. When a stamen stayed at the flower's centre, pollen removal of the
      next freely moved anther decreased significantly (P < 0.005) because of fewer
      touches by pollinators and quick leaving of pollinators that were discouraged by
      the empty anther. Simultaneous stamen movement occurred only in flowers with low
      pollen load on the stigma and the remaining pollen in anthers dropped onto stigma
      surfaces after stamens moved to the flower's centre. CONCLUSIONS: In R.
      graveolens pollen removal is promoted through one-by-one movement of the stamen,
      which presents pollen in doses to pollinators by successive uplifting of the
      stamen and avoids interference of two consecutively dehisced anthers by falling
      back of the former stamen before the next one moves into the flower's centre.
      Simultaneous stamen movement at the end of anthesis probably reflects an
      adaptation for late-acting self-pollination.

PMID- 22875814
TI  - Plasticity of stomatal distribution pattern and stem tracheid dimensions in
      Podocarpus lambertii: an ecological study.
AB  - BACKGROUND AND AIMS: Leaf and wood plasticity are key elements in the survival of
      widely distributed plant species. Little is known, however, about variation in
      stomatal distribution in the leaf epidermis and its correlation with the
      dimensions of conducting cells in wood. This study aimed at testing the
      hypothesis that Podocarpus lambertii, a conifer tree, possesses a well-defined
      pattern of stomatal distribution, and that this pattern can vary together with
      the dimensions of stem tracheids as a possible strategy to survive in
      climatically different sites. METHODS: Leaves and wood were sampled from trees
      growing in a cold, wet site in south-eastern Brazil and in a warm, dry site in
      north-eastern Brazil. Stomata were thoroughly mapped in leaves from each study
      site to determine a spatial sampling strategy. Stomatal density, stomatal index
      and guard cell length were then sampled in three regions of the leaf: near the
      midrib, near the leaf margin and in between the two. This sampling strategy was
      used to test for a pattern and its possible variation between study sites. Wood
      and stomata data were analysed together via principal component analysis. KEY
      RESULTS: The following distribution pattern was found in the south-eastern
      leaves: the stomatal index was up to 25 % higher in the central leaf region,
      between the midrib and the leaf margin, than in the adjacent regions. The inverse
      pattern was found in the north-eastern leaves, in which the stomatal index was 10
      % higher near the midrib and the leaf margin. This change in pattern was
      accompanied by smaller tracheid lumen diameter and length. CONCLUSIONS:
      Podocarpus lambertii individuals in sites with higher temperature and lower water
      availability jointly regulate stomatal distribution in leaves and tracheid
      dimensions in wood. The observed stomatal distribution pattern and variation
      appear to be closely related to the placement of conducting tissue in the
      mesophyll.

PMID- 22875815
TI  - Using flow cytometry to estimate pollen DNA content: improved methodology and
      applications.
AB  - BACKGROUND AND AIMS: Flow cytometry has been used to measure nuclear DNA content
      in pollen, mostly to understand pollen development and detect unreduced gametes.
      Published data have not always met the high-quality standards required for some
      applications, in part due to difficulties inherent in the extraction of nuclei.
      Here we describe a simple and relatively novel method for extracting pollen
      nuclei, involving the bursting of pollen through a nylon mesh, compare it with
      other methods and demonstrate its broad applicability and utility. METHODS: The
      method was tested across 80 species, 64 genera and 33 families, and the data were
      evaluated using established criteria for estimating genome size and analysing
      cell cycle. Filter bursting was directly compared with chopping in five species,
      yields were compared with published values for sonicated samples, and the method
      was applied by comparing genome size estimates for leaf and pollen nuclei in six
      species. KEY RESULTS: Data quality met generally applied standards for estimating
      genome size in 81 % of species and the higher best practice standards for cell
      cycle analysis in 51 %. In 41 % of species we met the most stringent criterion of
      screening 10 000 pollen grains per sample. In direct comparison with two chopping
      techniques, our method produced better quality histograms with consistently
      higher nuclei yields, and yields were higher than previously published results
      for sonication. In three binucleate and three trinucleate species we found that
      pollen-based genome size estimates differed from leaf tissue estimates by 1.5 %
      or less when 1C pollen nuclei were used, while estimates from 2C generative
      nuclei differed from leaf estimates by up to 2.5 %. CONCLUSIONS: The high success
      rate, ease of use and wide applicability of the filter bursting method show that
      this method can facilitate the use of pollen for estimating genome size and
      dramatically improve unreduced pollen production estimation with flow cytometry.

PMID- 22875816
TI  - The origin of the sporophyte shoot in land plants: a bryological perspective.
AB  - BACKGROUND: Land plants (embryophytes) are monophyletic and encompass four major
      clades: liverworts, mosses, hornworts and polysporangiophytes. The liverworts are
      resolved as the earliest divergent lineage and the mosses as sister to a crown
      clade formed by the hornworts and polysporangiophytes (lycophytes, monilophytes
      and seed plants). Alternative topologies resolving the hornworts as sister to
      mosses plus polysporangiophytes are less well supported. Sporophyte development
      in liverworts depends only on embryonic formative cell divisions. A transient
      basal meristem contributes part of the sporophyte in mosses. The sporophyte body
      in hornworts and polysporangiophytes develops predominantly by post-embryonic
      meristematic activity. SCOPE: This paper explores the origin of the sporophyte
      shoot in terms of changes in embryo organization. Pressure towards amplification
      of the sporangium-associated photosynthetic apparatus was a major driver of
      sporophyte evolution. Starting from a putative ancestral condition in which a
      transient basal meristem produced a sporangium-supporting seta, we postulate that
      in the hornwort-polysporangiophyte lineage the basal meristem acquired
      indeterminate meristematic activity and ectopically expressed the sporangium
      morphogenetic programme. The resulting sporophyte body plan remained
      substantially unaltered in hornworts, whereas in polysporangiophytes the
      persistent meristem shifted from a mid-embryo to a superficial position and was
      converted into an ancestral shoot apical meristem with the evolution of
      sequential vegetative and reproductive growth. CONCLUSIONS: The sporophyte shoot
      is interpreted as a sterilized sporangial axis interpolated between the embryo
      and the fertile sporangium. With reference to the putatively ancestral condition
      found in mosses, the sporophyte body plans in hornworts and polysporangiophytes
      are viewed as the product of opposite heterochronic events, i.e. an anticipation
      and a delay, respectively, in the development of the sporangium. In either case
      the result was a pedomorphic sporophyte permanently retaining juvenile
      characters.

PMID- 22875817
TI  - Temperature, stress and spontaneous mutation in Caenorhabditis briggsae and
      Caenorhabditis elegans.
AB  - Mutation rate often increases with environmental temperature, but establishing
      causality is complicated. Asymmetry between physiological stress and deviation
      from the optimal temperature means that temperature and stress are often
      confounded. We allowed mutations to accumulate in two species of Caenorhabditis
      for approximately 100 generations at 18 degrees C and for approximately 165
      generations at 26 degrees C; 26 degrees C is stressful for Caenorhabditis elegans
      but not for Caenorhabditis briggsae. We report mutation rates at a set of
      microsatellite loci and estimates of the per-generation decay of fitness
      (DeltaM(w)), the genomic mutation rate for fitness (U) and the average effect of
      a new mutation (E[a]), assayed at both temperatures. In C. elegans, the
      microsatellite mutation rate is significantly greater at 26 degrees C than at 18
      degrees C whereas in C. briggsae there is only a slight, non-significant increase
      in mutation rate at 26 degrees C, consistent with stress-dependent mutation in C.
      elegans. The fitness data from both species qualitatively reinforce the
      microsatellite results. The fitness results of C. elegans are potentially
      complicated by selection but also suggest temperature-dependent mutation; the
      difference between the two species suggests that physiological stress plays a
      significant role in the mutational process.

PMID- 22875818
TI  - Daphnia magna shows reduced infection upon secondary exposure to a pathogen.
AB  - Previous pathogen exposure is an important predictor of the probability of
      becoming infected. This is deeply understood for vertebrate hosts, and
      increasingly so for invertebrate hosts. Here, we test if an initial pathogen
      exposure changes the infection outcome to a secondary pathogen exposure in the
      natural host-pathogen system Daphnia magna and Pasteuria ramosa. Hosts were
      initially exposed to an infective pathogen strain, a non-infective pathogen
      strain or a control. The same hosts underwent a second exposure, this time to an
      infective pathogen strain, either immediately after the initial encounter or 48 h
      later. We observed that an initial encounter with a pathogen always conferred
      protection against infection compared with controls.

PMID- 22875819
TI  - Intralocus sexual conflict over human height.
AB  - Intralocus sexual conflict (IASC) occurs when a trait under selection in one sex
      constrains the other sex from achieving its sex-specific fitness optimum.
      Selection pressures on body size often differ between the sexes across many
      species, including humans: among men individuals of average height enjoy the
      highest reproductive success, while shorter women have the highest reproductive
      success. Given its high heritability, IASC over human height is likely. Using
      data from sibling pairs from the Wisconsin Longitudinal Study, we present
      evidence for IASC over height: in shorter sibling pairs (relatively) more
      reproductive success (number of children) was obtained through the sister than
      through the brother of the sibling pair. By contrast, in average height sibling
      pairs most reproductive success was obtained through the brother relative to the
      sister. In conclusion, we show that IASC over a heritable, sexually dimorphic
      physical trait (human height) affects Darwinian fitness in a contemporary human
      population.

PMID- 22875820
TI  - Pattern recognition: combining informatics and genetics to re-evaluate conduction
      disease.

PMID- 22875821
TI  - Aortic stenosis and the right heart at risk: is transcatheter aortic valve
      implantation the better option?

PMID- 22875822
TI  - Remote ischaemic preconditioning in coronary artery bypass surgery: a meta
      analysis.
AB  - AIM: Randomised trials exploring remote ischaemic preconditioning (RIPC) in
      patients undergoing coronary artery bypass graft (CABG) surgery have yielded
      conflicting data regarding potential cardiovascular and renal protection, and are
      individually flawed by small sample size. METHODS: Three investigators
      independently searched the MEDLINE, EMBASE and Cochrane databases to identify
      randomised trials testing RIPC in patients undergoing CABG. RESULTS: Nine studies
      with 704 patients were included. Standardised mean difference of troponin I and T
      release showed a significant decrease (-0.36 (95% CI -0.62 to -0.09)). This
      difference held true after excluding the trials with cross-clamp fibrillation,
      the study with off-pump CABG and studies using a flurane as anaesthetic agent (
      0.41 (95% CI -0.69 to -0.12), -0.38 (95% CI -0.70 to -0.07) and -0.37 (95% CI 
      0.63 to -0.12), respectively). A similar trend was also obtained for patients
      with multivessel disease (-0.41 (95% CI -0.73 to -0.08)). The trials evaluating
      postoperative creatinine reported a non-significant reduction (0.02 (95% CI -0.09
      to 0.13)). Moreover, the length of in-hospital stay was not influenced by the
      kind of treatment (weighted mean difference 0.27 (95% CI -0.24 to 0.79)).
      CONCLUSION: RIPC reduced the release of troponin in patients undergoing CABG.
      Larger randomised trials are needed to clarify the presence of a causal
      relationship between RIPC-induced troponin release and clinical adverse events.

PMID- 22875823
TI  - The multifaceted cardiac sodium channel and its clinical implications.

PMID- 22875824
TI  - Retraction: Notice of unreliable findings.

PMID- 22875825
TI  - Treating the leading killer.
AB  - Injection of a growth factor in a self-assembling nanofiber scaffold has the
      potential to create a suitable microenvironment and recruit endogenous cells for
      cardiac repair (Lin et al., this issue).

PMID- 22875826
TI  - The outsiders: emerging roles of ectonucleotidases in inflammation.
AB  - Research on the biological roles of ectonucleoidases has revealed that CD73, an
      ecto-5 nucleotidase, plays a special role in the extracellular conversion of
      adenosine monophosphate to adenosine--specifically, as a checkpoint that
      determines whether the extracellular environment is proinflammatory
      (characterized by adenosine 5'-triphosphate-mediated responses) or anti
      inflammatory (adenosine-mediated responses). Inactivating or inhibiting CD73
      attenuates the extracellular formation of adenosine, exacerbating the severity of
      various inflammatory diseases. In this issue of Science Translational Medicine,
      Flogel and colleagues showed that CD73 can be pharmacologically exploited to
      convert an inactive adenosine precursor to an active, anti-inflammatory adenosine
      analog. In addition to attenuating inflammation associated with collagen-induced
      arthritis in a mouse model, this prodrug approach was site-selective, because the
      metabolic conversion relies on CD73, which is up-regulated in the inflammatory
      locus (the joint).

PMID- 22875827
TI  - A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from
      Nipah virus challenge.
AB  - In the 1990s, Hendra virus and Nipah virus (NiV), two closely related and
      previously unrecognized paramyxoviruses that cause severe disease and death in
      humans and a variety of animals, were discovered in Australia and Malaysia,
      respectively. Outbreaks of disease have occurred nearly every year since NiV was
      first discovered, with case fatality ranging from 10 to 100%. In the African
      green monkey (AGM), NiV causes a severe lethal respiratory and/or neurological
      disease that essentially mirrors fatal human disease. Thus, the AGM represents a
      reliable disease model for vaccine and therapeutic efficacy testing. We show that
      vaccination of AGMs with a recombinant subunit vaccine based on the henipavirus
      attachment G glycoprotein affords complete protection against subsequent NiV
      infection with no evidence of clinical disease, virus replication, or pathology
      observed in any challenged subjects. Success of the recombinant subunit vaccine
      in nonhuman primates provides crucial data in supporting its further preclinical
      development for potential human use.

PMID- 22875828
TI  - Selective activation of adenosine A2A receptors on immune cells by a CD73
      dependent prodrug suppresses joint inflammation in experimental rheumatoid
      arthritis.
AB  - Adenosine A(2A) receptor (A(2A)R) agonists are both highly effective anti
      inflammatory agents and potent vasodilators. To separate these two activities, we
      have synthesized phosphorylated A(2A)R agonists (prodrugs) that require the
      presence of ecto-5'-nucleotidase (CD73) to become activated. In the model of
      collagen-induced arthritis, 2-(cyclohexylethylthio)adenosine 5'-monophosphate
      (chet-AMP), but not 2-(cyclohexylethylthio)adenosine (chet-adenosine), potently
      reduced inflammation as assessed by fluorine-19 ((19)F) magnetic resonance
      imaging and by histology. The prodrug effect was blunted by inhibition of CD73
      and A(2A)R. The selectivity of drug action is due to profound up-regulation of
      CD73 and adenosine A(2A)R expression in neutrophils and inflammatory monocytes as
      found in recovered cells from the synovial fluid of arthritic mice. Plasma chet
      adenosine was in the subnanomolar range when chet-AMP was applied, whereas
      concentrations required for vasodilation were about 100 times higher. Thus, chet
      AMP is a potent immunosuppressant with negligible vasodilatory activity. These
      data suggest that phosphorylated A(2A)R agonists may serve as a promising new
      group of drugs for targeted immunotherapy of inflammation.

PMID- 22875829
TI  - Instructive nanofiber scaffolds with VEGF create a microenvironment for
      arteriogenesis and cardiac repair.
AB  - Angiogenic therapy is a promising approach for tissue repair and regeneration.
      However, recent clinical trials with protein delivery or gene therapy to promote
      angiogenesis have failed to provide therapeutic effects. A key factor for
      achieving effective revascularization is the durability of the microvasculature
      and the formation of new arterial vessels. Accordingly, we carried out
      experiments to test whether intramyocardial injection of self-assembling peptide
      nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could
      create an intramyocardial microenvironment with prolonged VEGF release to improve
      post-infarct neovascularization in rats. Our data showed that when injected with
      NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the
      side effects of systemic edema and proteinuria were significantly reduced to the
      same level as that of control. NF/VEGF injection significantly improved
      angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial
      infarction. NF/VEGF injection not only allowed controlled local delivery but also
      transformed the injected site into a favorable microenvironment that recruited
      endogenous myofibroblasts and helped achieve effective revascularization. The
      engineered vascular niche further attracted a new population of cardiomyocyte
      like cells to home to the injected sites, suggesting cardiomyocyte regeneration.
      Follow-up studies in pigs also revealed healing benefits consistent with
      observations in rats. In summary, this study demonstrates a new strategy for
      cardiovascular repair with potential for future clinical translation.

PMID- 22875831
TI  - Caseous calcification of the mitral valve complicated by embolization, mitral
      regurgitation, and pericardial constriction.

PMID- 22875830
TI  - A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in
      rodents without producing dependence.
AB  - Buprenorphine, a synthetic opioid that acts at both MU and kappa opioid
      receptors, can decrease cocaine use in individuals with opioid addiction.
      However, the potent agonist action of buprenorphine at MU opioid receptors raises
      its potential for creating opioid dependence in non-opioid-dependent cocaine
      abusers. Here, we tested the hypothesis that a combination of buprenorphine and
      naltrexone (a potent MU opioid antagonist with weaker delta and kappa antagonist
      properties) could block compulsive cocaine self-administration without producing
      opioid dependence. The effects of buprenorphine and various doses of naltrexone
      on cocaine self-administration were assessed in rats that self-administered
      cocaine under conditions of either short access (noncompulsive cocaine seeking)
      or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly
      decreased cocaine self-administration. Although this buprenorphine-alone effect
      was blocked in a dose-dependent manner by naltrexone in both the short-access and
      the extended-access groups, the combination of the lowest dose of naltrexone with
      buprenorphine blocked cocaine self-administration in the extended-access group
      but not in the short-access group. Rats given this low dose of naltrexone with
      buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in
      rats treated with buprenorphine alone, and naltrexone at this dose did not block
      kappa agonist-induced analgesia. The results suggest that the combination of
      buprenorphine and naltrexone at an appropriate dosage decreases compulsive
      cocaine self-administration with minimal liability to produce opioid dependence
      and may be useful as a treatment for cocaine addiction.

PMID- 22875832
TI  - The experience of emotional distress among women with scleroderma.
AB  - Emotional distress is common among patients with chronic medical illnesses, but
      the nature of the distress is not well understood. Our objective was to
      understand patients' experiences of emotional distress by conducting in-depth
      interviews using the McGill Illness Narrative Interview with women affected by
      scleroderma (N = 16). We sought to determine how participants described their
      distress, what they believed caused it, and how they coped. We analyzed interview
      transcripts using thematic analysis. Many participants described distress
      associated with scleroderma, but the term depression was reserved for
      extraordinary, severe experiences. Instead, participants preferred more normal
      mood descriptors and often viewed their distress in keeping with the definition
      of "demoralization." Participants listed concrete symptoms and experiences that
      caused distress, and some added that stress could exacerbate scleroderma.
      Participants dealt with distress by not dwelling on their circumstances and
      working to maintain autonomy. Most preferred to not rely on psychologists and
      support groups.

PMID- 22875833
TI  - Gender bias undermines evidence on gender and health.

PMID- 22875834
TI  - Influence of new late effects on quality of life over time in Hodgkin lymphoma
      Survivors: a longitudinal survey study.
AB  - BACKGROUND: Long-term Hodgkin lymphoma (HL) survivors are known to have
      diminished quality of life (QoL). However, limited data are available on temporal
      changes in QoL and factors associated with the changes. METHODS: In 2010, we
      conducted a follow-up questionnaire study on 273 HL survivors who participated in
      a 2003 questionnaire study on late effects after HL. The questionnaire items were
      limited to new late complications and reassessment of QoL and fatigue level,
      using the Short Form 36 (SF-36) and the Functional Assessment of Chronic Illness
      Therapy-Fatigue instruments, respectively. We compared the results from the 2003
      and the 2010 questionnaires, and QoL score changes between survivors with and
      without new late complications during the 7-year period. RESULTS: There was a
      significant decline in the SF-36 Physical Component Summary score (median change,
      -1.8; P<0.0001) over the time period. The decline was significantly greater among
      survivors with a new cardiac (P=0.005) or pulmonary (P<0.0001) complication,
      compared with those without any new complications. The survivors reporting new
      cardiac complications also experienced significantly greater worsening of fatigue
      scores (P=0.004). CONCLUSION: The significant association between the development
      of new cardiopulmonary complications and decline in QoL and energy level of HL
      survivors provides further support for current efforts to reduce treatment to
      limit late effects.

PMID- 22875835
TI  - Reply to FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line
      treatment for patients with metastatic colorectal cancer-subgroup analysis of
      patients with KRAS-mutated tumours in the randomised German AIO study KRK-0306.

PMID- 22875836
TI  - Maternal and fetal outcomes of taxane chemotherapy in breast and ovarian cancer
      during pregnancy: case series and review of the literature.
AB  - BACKGROUND: The purpose of this study was to evaluate the use of taxane
      chemotherapy during pregnancy and compare maternal and neonatal outcomes with
      those in women who did not receive taxanes during pregnancy, and review current
      existing data. STUDY DESIGN: This is a retrospective cohort study in which women
      were identified from the Cancer and Pregnancy Registry at Robert Wood Johnson
      Medical Center. A retrospective chart analysis and an independent t-test were
      carried out comparing patient outcomes. A literature search in Ovid, Medline and
      PubMed was then carried out using the terms 'breast or ovarian cancer',
      'pregnancy', 'paclitaxel', 'docetaxel', 'taxanes' and 'chemotherapy'. RESULTS:
      Twelve of 129 women with breast cancer were exposed to taxanes during pregnancy.
      Three of nine women with ovarian cancer received taxane-based treatment during
      pregnancy. Birth weight, gestational age at delivery, rate of growth restriction,
      congenital anomalies and incidence of maternal and neonatal neutropenia were not
      statistically different between the two groups. CONCLUSIONS: Taxane-based
      chemotherapy does not appear to increase the risk of fetal or maternal
      complications when compared with conventional chemotherapy in the small cohort of
      women in our Registry.

PMID- 22875837
TI  - Whole-exome sequencing identifies mutations in the nucleoside transporter gene
      SLC29A3 in dysosteosclerosis, a form of osteopetrosis.
AB  - Dysosteosclerosis (DSS) is the form of osteopetrosis distinguished by the
      presence of skin findings such as red-violet macular atrophy, platyspondyly and
      metaphyseal osteosclerosis with relative radiolucency of widened diaphyses. At
      the histopathological level, there is a paucity of osteoclasts when the disease
      presents. In two patients with DSS, we identified homozygous or compound
      heterozygous missense mutations in SLC29A3 by whole-exome sequencing. This gene
      encodes a nucleoside transporter, mutations in which cause histiocytosis
      lymphadenopathy plus syndrome, a group of conditions with little or no skeletal
      involvement. This transporter is essential for lysosomal function in mice. We
      demonstrate the expression of Slc29a3 in mouse osteoclasts in vivo. In monocytes
      from patients with DSS, we observed reduced osteoclast differentiation and
      function (demineralization of calcium surface). Our report highlights the
      pleomorphic consequences of dysfunction of this nucleoside transporter, and
      importantly suggests a new mechanism for the control of osteoclast
      differentiation and function.

PMID- 22875838
TI  - Genetic-epigenetic interaction modulates MU-opioid receptor regulation.
AB  - Genetic and epigenetic mechanisms play important roles in protein expression,
      although at different levels. Genetic variations can alter CpG sites and thus
      influence the epigenetic regulation of mRNA expression, providing an increasingly
      recognized mechanism of functional consequences of genetic polymorphisms. One of
      those genetic effects is the association of reduced MU-opioid receptor expression
      with the functional genetic variant N40D (OPRM1 118A>G, rs1799971) that causes an
      amino acid exchange in the extracellular terminal of the MU-opioid receptor. We
      report that the nucleotide exchange at gene position +118 introduces a new CpG
      methylation site into the OPRM1 DNA at position +117. This leads to an enhanced
      methylation of the OPRM1 DNA at this site and downstream. This epigenetic
      mechanism impedes MU-opioid receptor upregulation in brain tissue of Caucasian
      chronic opiate addicts, assessed postmortem. While in wild-type subjects, a
      reduced signalling efficiency associated with chronic heroin exposure was
      compensated by an increased receptor density, this upregulation was absent in
      carriers of the 118G receptor variant due to a diminished OPRM1 mRNA
      transcription. Thus, the OPRM1 118A>G SNP variant not only reduces u-opioid
      receptor signalling efficiency, but, by a genetic-epigenetic interaction, reduces
      opioid receptor expression and therefore, depletes the opioid system of a
      compensatory reaction to chronic exposure. This demonstrates that a change in the
      genotype can cause a change in the epigenotype with major functional
      consequences.

PMID- 22875839
TI  - Unprotected fellatio between female sex workers and their clients in Sydney,
      Australia.
AB  - OBJECTIVES: To assess the frequency and predictors of inconsistent condom use for
      fellatio at work by female sex workers (FSW) in Sydney and the prevalence of
      pharyngeal gonorrhoea and other sexually transmitted infections in these women.
      METHODS: Cross-sectional study including all FSW attending the Sydney Sexual
      Health Centre for sexually transmitted infection screening between May 2009 and
      January 2011 and reporting fellatio at work. Univariate and multivariate
      regression was used to identify predictors of inconsistent condom use for
      fellatio. RESULTS: Of 1540 FSW who offered fellatio at work, 372 (25%) reported
      inconsistent condom use for this fellatio. In multivariate analysis, speaking
      Mandarin or Cantonese rather than English (adjusted OR (AOR) 2.03, 95% CI 1.44 to
      2.86), reporting inconsistent condom use for vaginal sex at work (AOR 10.82, 95%
      CI 6.13 to 19.09), reporting no vaginal sex at work (AOR 7.48, 95% CI 2.42 to
      23.12) and being a new client to the clinic (AOR 2.10, 95% CI 1.56 to 2.83) were
      associated with inconsistent condom use for fellatio. Thai-speaking women were
      less likely to report unprotected fellatio (AOR 0.36, 95% CI 0.23 to 0.57). 17
      women were diagnosed with pharyngeal gonorrhoea (AOR 1.1%, 95% CI 0.6% to 1.7%).
      CONCLUSIONS: Condom use for fellatio by Sydney FSW varies by work location and
      language spoken. Health promotion targeting these at-risk women is warranted.
      Women working in brothels masquerading as massage parlours were particularly
      likely to report inconsistent condom use for fellatio. Local government
      reluctance to approve brothels may be contributing to this problem.

PMID- 22875840
TI  - National audit of antidote stocking in acute hospitals in the UK.
AB  - BACKGROUND: Inadequate stocking of essential antidotes in hospitals for the
      treatment of poisoned patients has been reported worldwide. Joint National
      Poisons Information Service (NPIS)/College of Emergency Medicine (CEM) guidelines
      for antidote stocking in UK emergency departments and acute hospitals were
      published in 2008. AIM: To determine the impact of these guidelines by surveying
      the availability of antidotes in acute hospitals in the UK. METHODS: A two-page
      questionnaire consisting of antidote stocking information was distributed in 2010
      to the Chief Pharmacist in all acute hospitals in the UK. The availability of 28
      antidotes in the NPIS/CEM antidote guidelines as well as that of Intralipid was
      surveyed. RESULTS: Surveys were completed for 196 of the 224 (87.5%) hospitals.
      Over 90% of hospitals had acetylcysteine, activated charcoal, dantrolene,
      desferrioxamine, naloxone, flumazenil and vitamin K available within the
      recommended time period. Pralidoxime was reported to be held in only 33% of
      hospitals, though pralidoxime is supplied by the Department of Health to 95
      hospitals in the UK that act as holding centres. Cyproheptadine and viper venom
      antiserum were held in around 50% of acute hospitals. For the treatment of
      cyanide and toxic alcohol poisoning, more than one antidote is available. For
      cyanide poisoning, most hospitals held at least one antidote (usually dicobalt
      edetate) but 9 (5%) held none of the four antidotes. For toxic alcohol and glycol
      poisoning, most hospitals held ethanol for intravenous use but not fomepizole and
      30 (15%) did not stock any antidote for toxic alcohol poisoning. CONCLUSION:
      Stocking of less commonly used antidotes is inconsistent. This is likely to
      result in delayed access to treatment and worse patient outcomes.

PMID- 22875842
TI  - Moesin-deficient mice reveal a non-redundant role for moesin in lymphocyte
      homeostasis.
AB  - Moesin is a member of the ezrin-radixin-moesin (ERM) family of cytoskeletal
      proteins. These proteins organize membrane domains by interacting with plasma
      membrane proteins and the actin cytoskeleton. Because of their high sequence
      similarity, ERM proteins are usually thought to be functionally redundant.
      Lymphocytes express two ERM proteins, ezrin and moesin. Whether each ERM plays a
      specialized role in lymphocytes, particularly in vivo, remains unknown. Here, we
      show that moesin has a crucial, non-redundant role in lymphocyte homeostasis.
      Moesin-deficient mice exhibited decreases in both T and B cells in the peripheral
      blood and lymph nodes, but not in the spleen. This phenotype was recapitulated in
      bone marrow (BM) chimeras with a hematopoietic moesin deficiency. Although the T
      and B cells apparently developed without major defects in the moesin-deficient
      mice, T cell egress from the thymus and immature B cell egress from the BM were
      impaired. In the periphery, both T and B cells showed delayed egress from
      lymphoid organs. We showed that moesin is the primary phosphorylated ERM subject
      to dynamic regulation during cell shape changes and migration. Our findings
      identify a previously unknown, non-redundant function of moesin in lymphocyte
      homeostasis in regulating lymphocyte egress from lymphoid organs.

PMID- 22875843
TI  - SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated
      activation of basophils.
AB  - Basophils have been reported to play a critical role in allergic inflammation by
      secreting IL-4 in response to IL-3 or high-affinity IgE receptor (FcepsilonRI)
      cross-linking. However, the signaling pathways downstream of FcepsilonRI and the
      IL-3 receptor in basophils have yet to be determined. In the present study, we
      used mice deficient in SLP-76 (Src homology 2 domain-containing leukocyte
      phosphoprotein of 76kDa) to demonstrate critical functions of this adaptor
      molecule in transducing FcepsilonRI- and IL-3 receptor-mediated signals that
      induce basophil activation. Although SLP-76 was dispensable for in vivo
      differentiation, as well as IL-3-induced in vitro proliferation of basophils, IL
      4 production induced by both stimuli was completely ablated by SLP-76 deficiency.
      Biochemical analyses revealed that IL-3-induced phosphorylation of phospholipase
      C (PLC) gamma2 and Akt, but not STAT5, was severely reduced in SLP-76-deficient
      basophils, whereas FcepsilonRI cross-linking phosphorylation of PLCgamma2, but
      not Akt, was abrogated by SLP-76 deficiency, suggesting important differences in
      the requirement of SLP-76 for Akt activation between FcepsilonRI- and IL-3
      receptor-mediated signaling pathways in basophils. Because IL-3-induced IL-4
      production was sensitive to calcineurin inhibitors and an intracellular calcium
      chelator, in addition to PI3K inhibitors, SLP-76 appears to regulate FcepsilonRI-
      and IL-3 receptor-induced IL-4 production via mediating PLCgamma2 activation in
      basophils. Taken together, these findings indicate that SLP-76 is an essential
      signaling component for basophil activation downstream of both FcepsilonRI and
      the IL-3 receptor.

PMID- 22875844
TI  - Risk recognition and sensation seeking in revictimization and posttraumatic
      stress disorder.
AB  - Impaired risk recognition has been suggested to be associated with the risk for
      revictimization and the development of posttraumatic stress disorder (PTSD).
      Moreover, risk behavior has been linked to high sensation seeking, which may also
      increase the probability of revictimization. A newly designed behavioral
      experiment with five audiotaped risk scenarios was used to investigate risk
      recognition in revictimized, single-victimized, and nontraumatized individuals
      with and without PTSD. Moreover, the potential role of sensation seeking in
      revictimization, and PTSD as well as its relation to risk recognition was
      explored. Revictimized, single-victimized, and nontraumatized individuals did not
      differ with regard to general risk recognition. However, delayed risk recognition
      was found for the revictimized group when arousal ratings were considered. No
      differences in sensation seeking were found between the three groups; only the
      nontraumatized group showed lower boredom susceptibility relative to the
      revictimized group. Delayed risk recognition was associated with high sensation
      seeking. Furthermore, PTSD symptoms significantly predicted exit levels of risk
      scenarios. Findings are discussed against the background of previous research.

PMID- 22875845
TI  - 17beta-estradiol protects 7-day old rats from acute brain injury and reduces the
      number of apoptotic cells.
AB  - OBJECTIVE: To test a possible neuroprotective activity of 17beta-estradiol in the
      neonatal rat brain exposed to hypoxic-ischemia (controlled hypoxia after
      unilateral carotid artery ligation). METHODS: Seven-day-old Wistar rats underwent
      ligation of the left common carotid artery followed by 80 minutes hypoxia in 8%
      oxygen inducing an ipsilateral brain damage. Seven days later (d14), brains were
      analyzed quantitatively using a macroscopic and microscopic score for structural
      damage, hemisphere volumes were calculated, and immunohistochemistry for cleaved
      caspase-3 (marker for apoptotic cells) was performed. Animals from the study
      group (n = 19) received 17beta-estradiol (0.05 ug/g body weight
      intraperitoneally) before (-64, -40, and -16 hours) and after (+3 hours) the
      hypoxia (hour 0: start of the hypoxia) and the control group (n = 21) received
      mock treatment. RESULTS: Of the 21 pups, 13 in the NaCl group had macroscopically
      a severe brain damage and 7 of 19 animals in the study group encountered only
      discrete to mild lesions. Microscopic brain damage in the study group was
      significantly lower (score 1.5 +/- 0.7 vs 2.8 +/- 0.8, P < .05). The determined
      volumes of the affected hemisphere were significantly lower in the NaCl group
      than in the treatment group. The numbers of apoptotic cells in both hemispheres
      was equal in the estradiol group, but in the control group, there were
      significantly more apoptotic cells in the affected hemisphere (control group:
      ipsilateral: 1435 +/- 653 vs contralateral: 143 +/- 57 cells, P < .05).
      DISCUSSION: 17beta-Estradiol protects newborn rat brains from hypoxic-ischemic
      injury, in terms of both microscopic cell injury and apoptosis.

PMID- 22875846
TI  - 2-methoxyestradiol in the pathophysiology of endometriosis: focus on angiogenesis
      and therapeutic potential.
AB  - Endometriosis is a common condition among women of childbearing potential in
      which ectopic endometrial tissue is found outside the uterine cavity.
      Neoangiogenesis plays a major role in the development of endometriotic implants.
      Some evidence suggests that a disorder in the balance of proangiogenic and
      antiangiogenic factors that favors the former is induced by local hypoxia and is
      mediated by the hypoxia-inducible factor-vascular endothelium growth factor
      pathway could partially explain the development of this condition in some women.
      2-methoxyestradiol is a biologically active metabolite of estradiol having
      antiangiogenic action. Changes in estradiol homeostasis have been locally
      observed in endometriosis. In this review, we summarize current knowledge of
      endometriosis pathophysiology, in particular, the balance between local 2
      methoxyestradiol production and angiogenesis, which could promote the development
      of endometriotic lesions. 2-Methoxyestradiol emerges as a promising new candidate
      for the treatment of endometriosis.

PMID- 22875847
TI  - Slit2 overexpression results in increased microvessel density and lesion size in
      mice with induced endometriosis.
AB  - We recently reported that Slit/Roundabout (ROBO) 1 pathway may be a constituent
      biomarker for recurrence of endometriosis, likely through promoting angiogenesis.
      In this study, we sought to determine as whether Slit2 overexpression can
      facilitate angiogenesis, increase lesion size, and induce hyperalgesia in mice
      with induced endometriosis. We used 30 Slit2 transgenic (S) and 29 wild-type (W)
      mice and cross-transplanted endometrial fragments from S to W (group SW) and vice
      versa (group WS), and also within the S and W (groups SS and WW, respectively),
      into the peritoneal cavity, inducing endometriosis. We also performed a sham
      surgery within both S and W mice (groups Sm and Wm, respectively). The size of
      the ectopic implants, microvessel density (MVD) and immunoreactivity to ROBO1,
      and vascular endothelial cell growth factor (VEGF) in ectopic and eutopic
      endometrium, along with hotplate and tail-flick tests in all mice, were then
      evaluated. We found that the induction of endometriosis resulted in generalized
      hyperalgesia, which was unaffected by Slit2 overexpression. Slit2 overexpression
      did increase the lesion size significantly and correlated positively with the MVD
      in ectopic and eutopic endometrium. Slit2 expression levels appear to correlate
      with the MVD, but not with VEGF immunoreactivity, in ectopic endometrium.
      Consequently, we conclude that Slit2 may play an important role in angiogenesis
      in endometriosis. The increased angiogenesis, as measured by MVD, but not VEGF
      immunoreactivity, likely resulted in increased lesion size in induced
      endometriosis. Thus, SLIT2/ROBO1 pathway may be a potential therapeutic target
      for treating endometriosis.

PMID- 22875848
TI  - Expression of the GTP-binding protein Galphas in human myometrial cells is
      regulated by ubiquitination and protein degradation: involvement of proteasomal
      inhibition by trichostatin A.
AB  - In this study, we show that myometrial transcriptional complexes consisting of
      Sp1, Sp3, histone deacetylase (HDAC)1/2, RbAp48, and mSin3A are recruited to 4
      out of the 6 Sp1-4 sites within the Galphas promoter. Moreover disruption in the
      binding of these complexes via mithramycin administration results in a
      substantial decrease in expression of Galphas proteins in myometrial cell
      cultures. In many instances, these transcriptional regulatory complexes repress
      expression of genes having a high CG content within their promoter region. This
      repression can be attenuated by inhibition of HDAC activity by the class I/II
      HDAC inhibitor trichostatin A (TSA) resulting in increased gene transcription.
      However, although a substantial increase in Galphas protein levels was observed
      upon administration of TSA to primary cultures of human myometrial cells, this
      was not preceded by an increase in messenger RNA (mRNA) and thus an elevation in
      gene transcription. Importantly the increase in Galphas protein levels occurred
      via ubiquitination and inhibition of proteasomal activity, indicating that this
      pathway is also involved in regulating Galphas protein expression during
      pregnancy and parturition.

PMID- 22875849
TI  - Sulfamethoxazole enhances the antimycobacterial activity of rifampicin.
AB  - OBJECTIVES: To investigate the effect of trimethoprim/sulfamethoxazole on the
      survival of Mycobacterium tuberculosis and trimethoprim and sulfamethoxazole
      individually and combined with the first-line tuberculosis drugs (isoniazid,
      rifampicin and ethambutol). METHODS: M. tuberculosis strains were exposed to
      either trimethoprim/sulfamethoxazole combination or sulfamethoxazole and
      trimethoprim alone at various concentrations. The strains were also exposed to
      sulfamethoxazole in combination with existing antibiotics to assess the combined
      effect on the growth of M. tuberculosis in the BACTEC 460TB system. The effect of
      the drugs was compared with vehicle-treated controls. Drug interactions were
      interpreted using quotient values obtained from the growth index of cultures
      treated with a single drug or the combination. RESULTS: Trimethoprim showed a
      negligible effect on the growth of M. tuberculosis while sulfamethoxazole
      inhibited 80% of the growth of M. tuberculosis at 4.75 mg/L. There was no
      synergistic activity between sulfamethoxazole and trimethoprim, although an
      additive effect was observed. A statistically significant synergistic effect was
      observed between sulfamethoxazole and rifampicin. Sulfamethoxazole also had an
      additive effect with ethambutol, but there was no interaction with isoniazid.
      CONCLUSIONS: Sulfamethoxazole is the main active compound against M. tuberculosis
      in the combination trimethoprim/sulfamethoxazole and has a synergistic effect
      with rifampicin. These findings suggest that sulfamethoxazole has potential in
      the multidrug regimen against M. tuberculosis.

PMID- 22875850
TI  - Activity of delafloxacin against methicillin-resistant Staphylococcus aureus:
      resistance selection and characterization.
AB  - OBJECTIVES: To determine the potential for delafloxacin to select for resistant
      mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates
      with existing mutations in the quinolone resistance determining region (QRDR).
      METHODS: Susceptibility testing by broth microdilution was performed on 30 MRSA
      clinical isolates. For four of these isolates, the presence or absence of
      mutations in the QRDR was characterized. Resistance selection was performed on
      these four isolates by spreading cells on drug-containing agar plates followed by
      incubation for 48 h. Resistance frequencies and mutant prevention concentrations
      (MPCs) were calculated for each; PCR amplification and sequencing were performed
      using standard methods to characterize mutations in the QRDR. Growth rate
      analysis was performed and relative fitness was determined. RESULTS: Delafloxacin
      demonstrated potent in vitro activity against this set of MRSA isolates, with
      MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L,
      respectively. Spontaneous delafloxacin resistance frequencies for the MRSA
      strains were 2 * 10(-9) to <9.5 * 10(-11). Delafloxacin MPCs were one to four
      times the MIC for any isolate, lower than those of comparator quinolones. Some
      delafloxacin-selected mutants showed a fitness cost when co-cultured with the
      parent strain. CONCLUSIONS: Delafloxacin demonstrates excellent antibacterial
      potency and exhibits a low probability for the selection of resistant mutants in
      MRSA. Although mutants can be selected at low frequencies in vitro from quinolone
      resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can
      be observed. Consequently delafloxacin warrants further investigation for the
      potential treatment of drug-resistant MRSA infections.

PMID- 22875851
TI  - Techniques of bronchial sleeve resection.
AB  - A bronchial sleeve resection can be considered for lesions arising from a lobar
      bronchus so as to preclude a standard lobectomy, yet without enough distal
      involvement as to warrant a pneumonectomy. Limited bronchial resection allows
      maximal conservation of pulmonary function in patients with benign or malignant
      disease, without compromising oncologic outcome. This article defines the
      indications and preoperative management of candidate patients and discusses key
      anesthetic considerations and surgical techniques for this complex airway
      reconstruction. The essential component of a successful operation is a tension
      free bronchial anastomosis. Open communication and careful discussion of airway
      management between anesthesiologist and surgeon will help ensure a good outcome.

PMID- 22875852
TI  - Biosynthesis of the polymannose lipopolysaccharide O-antigens from Escherichia
      coli serotypes O8 and O9a requires a unique combination of single- and multiple
      active site mannosyltransferases.
AB  - The Escherichia coli O9a and O8 O-antigen serotypes represent model systems for
      the ABC transporter-dependent synthesis of bacterial polysaccharides. The O9a and
      O8 antigens are linear mannose homopolymers containing conserved reducing termini
      (the primer-adaptor), a serotype-specific repeat unit domain, and a terminator.
      Synthesis of these glycans occurs on the polyisoprenoid lipid-linked primer,
      undecaprenol pyrophosphoryl-GlcpNAc, by two conserved mannosyltransferases, WbdC
      and WbdB, and a serotype-specific mannosyltransferase, WbdA. The glycan structure
      and pattern of conservation in the O9a and O8 mannosyltransferases are not
      consistent with the existing model of O9a biosynthesis. Here we establish a
      revised pathway using a combination of in vivo (mutant complementation)
      experiments and in vitro strategies with purified enzymes and synthetic
      acceptors. WbdC and WbdB synthesize the adaptor region, where they transfer one
      and two alpha-(1->3)-linked mannose residues, respectively. The WbdA enzymes are
      solely responsible for forming the repeat unit domains of these O-antigens.
      WbdA(O9a) has two predicted active sites and polymerizes a tetrasaccharide repeat
      unit containing two alpha-(1->3)- and two alpha-(1->2)-linked mannopyranose
      residues. In contrast, WbdA(O8) polymerizes trisaccharide repeat units containing
      single alpha-(1->3)-, alpha-(1->2)-, and beta-(1->2)-mannopyranoses. These
      studies illustrate assembly systems exploiting several mannosyltransferases with
      flexible active sites, arranged in single- and multiple-domain formats.

PMID- 22875853
TI  - Transcriptional network analysis identifies BACH1 as a master regulator of breast
      cancer bone metastasis.
AB  - The application of functional genomic analysis of breast cancer metastasis has
      led to the identification of a growing number of organ-specific metastasis genes,
      which often function in concert to facilitate different steps of the metastatic
      cascade. However, the gene regulatory network that controls the expression of
      these metastasis genes remains largely unknown. Here, we demonstrate a
      computational approach for the deconvolution of transcriptional networks to
      discover master regulators of breast cancer bone metastasis. Several known
      regulators of breast cancer bone metastasis such as Smad4 and HIF1 were
      identified in our analysis. Experimental validation of the networks revealed
      BACH1, a basic leucine zipper transcription factor, as the common regulator of
      several functional metastasis genes, including MMP1 and CXCR4. Ectopic expression
      of BACH1 enhanced the malignance of breast cancer cells, and conversely, BACH1
      knockdown significantly reduced bone metastasis. The expression of BACH1 and its
      target genes was linked to the higher risk of breast cancer recurrence in
      patients. This study established BACH1 as the master regulator of breast cancer
      bone metastasis and provided a paradigm to identify molecular determinants in
      complex pathological processes.

PMID- 22875854
TI  - Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant
      negative effects, and low density lipoprotein receptor (LDLR) degradation.
AB  - The proprotein convertase PCSK9 is a major target in the treatment of
      hypercholesterolemia because of its ability bind the LDL receptor (LDLR) and
      enhance its degradation in endosomes/lysosomes. In the endoplasmic reticulum, the
      zymogen pro-PCSK9 is first autocatalytically cleaved at its internal Gln(152)?,
      resulting in a secreted enzymatically inactive complex of PCSK9 with its
      inhibitory prosegment (prosegment.PCSK9), which is the active form of PCSK9 on
      the LDLR. We mutagenized the P1 cleavage site Gln(152) into all other residues
      except Cys and analyzed the expression and secretion of the resulting mutants.
      The data demonstrated the following. 1) The only P1 residues recognized by PCSK9
      are Gln > Met > Ala > Ser > Thr ~ Asn, revealing an unsuspected specificity. 2)
      All other mutations led to the formation of an unprocessed zymogen that acted as
      a dominant negative retaining the native protein in the endoplasmic reticulum.
      Analysis of a large panoply of known natural and artificial point mutants
      revealed that this general dominant negative observation applies to all PCSK9
      mutations that result in the inability of the protein to exit the endoplasmic
      reticulum. Such a tight quality control property of the endoplasmic reticulum may
      lead to the development of specific PCSK9 small molecule inhibitors that block
      its autocatalytic processing. Finally, inspired by the most active gain-of
      function mutant, D374Y, we evaluated the LDLR degradation activity of 18 Asp(374)
      variants of PCSK9. All Asp(374) mutations resulted in similar gain-of-function
      activity on the LDLR except that D374E was as active as native PCSK9, D374G was
      relatively less active, and D374N and D374P were completely inactive.

PMID- 22875855
TI  - Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced
      gene 2 (GPR183).
AB  - Oxysterols are oxygenated cholesterol derivates that are emerging as a
      physiologically important group of molecules. Although they regulate a range of
      cellular processes, only few oxysterol-binding effector proteins have been
      identified, and the knowledge of their binding mode is limited. Recently, the
      family of G protein-coupled seven transmembrane-spanning receptors (7TM
      receptors) was added to this group. Specifically, the Epstein-Barr virus-induced
      gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most
      potently by 7alpha,25-dihydroxycholesterol (7alpha,25-OHC). Nothing is known
      about the binding mode, however. Using mutational analysis, we identify here four
      key residues for 7alpha,25-OHC binding: Arg-87 in TM-II (position II:20/2.60),
      Tyr-112 and Tyr-116 (positions III:09/3.33 and III:13/3.37) in TM-III, and Tyr
      260 in TM-VI (position VI:16/6.51). Substituting these residues with Ala and/or
      Phe results in a severe decrease in agonist binding and receptor activation.
      Docking simulations suggest that Tyr-116 interacts with the 3beta-OH group in the
      agonist, Tyr-260 with the 7alpha-OH group, and Arg-87, either directly or
      indirectly, with the 25-OH group, although nearby residues likely also
      contribute. In addition, Tyr-112 is involved in 7alpha,25-OHC binding but via
      hydrophobic interactions. Finally, we show that II:20/2.60 constitutes an
      important residue for ligand binding in receptors carrying a positively charged
      residue at this position. This group is dominated by lipid- and nucleotide
      activated receptors, here exemplified by the CysLTs, P2Y12, and P2Y14. In
      conclusion, we present the first molecular characterization of oxysterol binding
      to a 7TM receptor and identify position II:20/2.60 as a generally important
      residue for ligand binding in certain 7TM receptors.

PMID- 22875856
TI  - Endoplasmic reticulum stress pathway required for immune homeostasis is neurally
      controlled by arrestin-1.
AB  - In response to pathogen infection, the host innate immune system activates
      microbial killing pathways and cellular stress pathways that need to be balanced
      because insufficient or excessive immune responses have deleterious consequences.
      Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the
      nervous system of Caenorhabditis elegans control immune homeostasis. To
      investigate further how GPCR signaling controls immune homeostasis at the
      organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor
      protein in C. elegans. The results indicate that ARR-1 is required for GPCR
      signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded
      protein response and a p38 mitogen-activated protein kinase signaling pathway
      required for innate immunity. ARR-1 activity also controlled immunity through ADF
      chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore,
      we found that although ARR-1 played a key role in the control of immunity by AFD
      thermosensory neurons, it did not control longevity through these cells. However,
      ARR-1 partially controlled longevity through ADF neurons.

PMID- 22875858
TI  - Critical period of experience-driven axon retraction in the pharmacologically
      inhibited visual cortex.
AB  - Monocular deprivation (MD) during the critical period reduces the visual cortical
      response to the deprived eye and causes the geniculocortical axons serving the
      deprived eye to retract. When MD is combined with a pharmacological inhibition of
      the visual cortex, the cortical neurons weaken their response to an open eye and
      the input axons serving the open eye retract. To determine whether the 2 types of
      ocular dominance (OD) plasticity reflect an experience-driven modification of
      neural circuits sharing the same developmental time course, we analyzed the OD
      plasticity in an inhibited visual cortex using cats at different ages. MD did not
      affect the OD distribution in the inhibited cortex of adults, confirming that the
      OD plasticity in the inhibited cortex represents a developmental plasticity. In
      developing animals, the OD plasticity in the inhibited cortex was observed at the
      late phase of the critical period (P40-46) but not at the early phase (P22-26).
      We found a retraction of input axons serving an open eye at the late phase,
      whereas those at the early phase were comparable to the axons of normal animals.
      Therefore, the maturation of visual circuits might include an experience-driven
      rearrangement of thalamocortical projections during the late phase of
      development. 

PMID- 22875857
TI  - Functional significance of atypical cortical organization in spina bifida
      myelomeningocele: relations of cortical thickness and gyrification with IQ and
      fine motor dexterity.
AB  - The cortex in spina bifida myelomeningocele (SBM) is atypically organized, but it
      is not known how specific features of atypical cortical organization promote or
      disrupt cognitive and motor function. Relations of deviant cortical thickness and
      gyrification with IQ and fine motor dexterity were investigated in 64 individuals
      with SBM and 26 typically developing (TD) individuals, aged 8-28 years. Cortical
      thickness and 3D local gyrification index (LGI) were quantified from 33 cortical
      regions per hemisphere using FreeSurfer. Results replicated previous findings,
      showing regions of higher and lower cortical thickness and LGI in SBM relative to
      the TD comparison individuals. Cortical thickness and LGI were negatively
      associated in most cortical regions, though less consistently in the TD group.
      Whereas cortical thickness and LGI tended to be negatively associated with IQ and
      fine motor outcomes in regions that were thicker or more gyrified in SBM,
      associations tended to be positive in regions that were thinner or less gyrified
      in SBM. The more deviant the levels of cortical thickness and LGI-whether higher
      or lower relative to the TD group-the more impaired the IQ and fine motor
      outcomes, suggesting that these cortical atypicalities in SBM are functionally
      maladaptive, rather than adaptive. 

PMID- 22875859
TI  - Category-specific neural oscillations predict recall organization during memory
      search.
AB  - Retrieved-context models of human memory propose that as material is studied,
      retrieval cues are constructed that allow one to target particular aspects of
      past experience. We examined the neural predictions of these models by using
      electrocorticographic/depth recordings and scalp electroencephalography (EEG) to
      characterize category-specific oscillatory activity, while participants studied
      and recalled items from distinct, neurally discriminable categories. During
      study, these category-specific patterns predict whether a studied item will be
      recalled. In the scalp EEG experiment, category-specific activity during study
      also predicts whether a given item will be recalled adjacent to other same
      category items, consistent with the proposal that a category-specific retrieval
      cue is used to guide memory search. Retrieved-context models suggest that
      integrative neural circuitry is involved in the construction and maintenance of
      the retrieval cue. Consistent with this hypothesis, we observe category-specific
      patterns that rise in strength as multiple same-category items are studied
      sequentially, and find that individual differences in this category-specific
      neural integration during study predict the degree to which a participant will
      use category information to organize memory search. Finally, we track the
      deployment of this retrieval cue during memory search: Category-specific patterns
      are stronger when participants organize their responses according to the category
      of the studied material. 

PMID- 22875860
TI  - Theta signal as the neural signature of social exclusion.
AB  - The feeling of being excluded from a social interaction triggers social pain, a
      sensation as intense as actual physical pain. Little is known about the
      neurophysiological underpinnings of social pain. We addressed this issue using
      intracranial electroencephalography in 15 patients performing a ball game where
      inclusion and exclusion blocks were alternated. Time-frequency analyses showed an
      increase in power of theta-band oscillations during exclusion in the anterior
      insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC),
      and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast
      response to exclusion but the signal rapidly faded out. Activity in the sACC
      gradually increased and remained significant thereafter. This suggests that the
      AI may signal social pain by detecting emotional distress caused by the
      exclusion, whereas the sACC may be linked to the learning aspects of social pain.
      Theta activity in the FFA was time-locked to the observation of a player poised
      to exclude the participant, suggesting that the FFA encodes the social value of
      faces. Taken together, our findings suggest that theta activity represents the
      neural signature of social pain. The time course of this signal varies across
      regions important for processing emotional features linked to social information.

PMID- 22875861
TI  - The development of hub architecture in the human functional brain network.
AB  - Functional hubs are brain regions that play a crucial role in facilitating
      communication among parallel, distributed brain networks. The developmental
      emergence and stability of hubs, however, is not well understood. The current
      study used measures of network topology drawn from graph theory to investigate
      the development of functional hubs in 99 participants, 10-20 years of age. We
      found that hub architecture was evident in late childhood and was stable from
      adolescence to early adulthood. Connectivity between hub and non-hub ("spoke")
      regions, however, changed with development. From childhood to adolescence, the
      strength of connections between frontal hubs and cortical and subcortical spoke
      regions increased. From adolescence to adulthood, hub-spoke connections with
      frontal hubs were stable, whereas connectivity between cerebellar hubs and
      cortical spoke regions increased. Our findings suggest that a developmentally
      stable functional hub architecture provides the foundation of information flow in
      the brain, whereas connections between hubs and spokes continue to develop,
      possibly supporting mature cognitive function. 

PMID- 22875862
TI  - Dendritic morphology of pyramidal neurons in the chimpanzee neocortex: regional
      specializations and comparison to humans.
AB  - The primate cerebral cortex is characterized by regional variation in the
      structure of pyramidal neurons, with more complex dendritic arbors and greater
      spine density observed in prefrontal compared with sensory and motor cortices.
      Although there are several investigations in humans and other primates, virtually
      nothing is known about regional variation in the morphology of pyramidal neurons
      in the cerebral cortex of great apes, humans' closest living relatives. The
      current study uses the rapid Golgi stain to quantify the dendritic structure of
      layer III pyramidal neurons in 4 areas of the chimpanzee cerebral cortex: Primary
      somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and
      prefrontal (area 10) cortex. Consistent with previous studies in humans and
      macaque monkeys, pyramidal neurons in the prefrontal cortex of chimpanzees
      exhibit greater dendritic complexity than those in other cortical regions,
      suggesting that prefrontal cortical evolution in primates is characterized by
      increased potential for integrative connectivity. Compared with chimpanzees, the
      pyramidal neurons of humans had significantly longer and more branched dendritic
      arbors in all cortical regions. 

PMID- 22875864
TI  - Orbitofrontal cortex and olfactory bulb volume predict distinct aspects of
      olfactory performance in healthy subjects.
AB  - While recent studies suggest an important role of higher order olfactory brain
      areas for basic olfactory performance, the extent to which cortical and
      peripheral neural markers account for separate portions of the variability in
      olfactory perceptual acuity is still unclear. We addressed this question by
      correlating voxel-based morphometry data from 90 healthy adults with olfactory
      performance measures. Supplementing this approach with region of interest (ROI)
      analyses of functionally defined olfactory cortical regions and olfactory bulb
      volume, we sought to disentangle the relative contribution of central and
      peripheral areas to behavioral variability. Whole-brain analyses revealed a
      significant positive correlation of gray matter volume and olfactory function
      scores in the right orbital sulcus. This effect was confirmed by the ROI
      analyses, which further indicated a significant association of the olfactory
      score with olfactory bulb volume. Moreover, a functional dissociation was
      observed, with central and peripheral mechanisms explaining different aspects of
      the observed behavioral variance in the olfactory subscores. In line with
      previous clinical studies, these data thus suggest an important role of regional
      gray matter volume in the right orbitofrontal cortex and olfactory bulb volume
      for olfactory performance in healthy individuals. 

PMID- 22875863
TI  - Modeling ketamine effects on synaptic plasticity during the mismatch negativity.
AB  - This paper presents a model-based investigation of mechanisms underlying the
      reduction of mismatch negativity (MMN) amplitudes under the NMDA-receptor
      antagonist ketamine. We applied dynamic causal modeling and Bayesian model
      selection to data from a recent ketamine study of the roving MMN paradigm, using
      a cross-over, double-blind, placebo-controlled design. Our modeling was guided by
      a predictive coding framework that unifies contemporary "adaptation" and "model
      adjustment" MMN theories. Comparing a series of dynamic causal models that
      allowed for different expressions of neuronal adaptation and synaptic plasticity,
      we obtained 3 major results: 1) We replicated previous results that both
      adaptation and short-term plasticity are necessary to explain MMN generation per
      se; 2) we found significant ketamine effects on synaptic plasticity, but not
      adaptation, and a selective ketamine effect on the forward connection from left
      primary auditory cortex to superior temporal gyrus; 3) this model-based estimate
      of ketamine effects on synaptic plasticity correlated significantly with ratings
      of ketamine-induced impairments in cognition and control. Our modeling approach
      thus suggests a concrete mechanism for ketamine effects on MMN that correlates
      with drug-induced psychopathology. More generally, this demonstrates the
      potential of modeling for inferring on synaptic physiology, and its
      pharmacological modulation, from electroencephalography data. 

PMID- 22875865
TI  - Rethinking the role of the middle longitudinal fascicle in language and auditory
      pathways.
AB  - The middle longitudinal fascicle (MdLF) was originally described in the monkey
      brain as a pathway that interconnects the superior temporal and angular gyri.
      Only recently have diffusion tensor imaging studies provided some evidence of its
      existence in humans, with a connectivity pattern similar to that in monkeys and a
      potential role in the language system. In this study, we combine high-angular
      resolution fiber tractography and fiber microdissection techniques to determine
      the trajectory, cortical connectivity, and a quantitative analysis of the MdLF.
      Here, we analyze diffusion spectrum imaging (DSI) studies in 6 subjects (subject
      specific approach) and in a template of 90 DSI studies (NTU-90 Atlas). Our
      tractography and microdissection results show that the human MdLF differs
      significantly from the monkey. Indeed, the human MdLF interconnects the superior
      temporal gyrus with the superior parietal lobule and parietooccipital region, and
      has only minor connections with the angular gyrus. On the basis of the roles of
      these interconnected cortical regions, we hypothesize that, rather than a
      language-related tract, the MdLF may contribute to the dorsal "where" pathway of
      the auditory system. 

PMID- 22875866
TI  - Feature-based attention affects direction-selective fMRI adaptation in hMT+.
AB  - Functional magnetic resonance adaptation has been successfully used to reveal
      direction-selective responses in the human motion complex (hMT+). Here, we aimed
      at further investigating direction-selective as well as position-selective
      responses of hMT+ by looking at how these responses are affected by feature-based
      attention. We varied motion direction and position of 2 consecutive random-dot
      stimuli. Participants had to either attend to the direction or the position of
      the stimuli in separate runs. We show that direction selectivity in hMT+ as
      measured by functional magnetic resonance imaging (fMRI) adaptation was strongly
      influenced by task set. Attending to the motion direction of the stimuli lead to
      stronger direction-selective fMRI adaptation than attending to their position.
      Position selectivity, on the other hand, was largely unaffected by attentional
      focus. Interestingly, the change in the direction-selective adaptation profile
      across tasks could not be explained by inheritance from earlier areas. The
      response pattern in the early retinotopic cortex was stable across conditions. In
      conclusion, our results provide further evidence for the flexible coding of
      direction information in hMT+ depending on task demands. 

PMID- 22875867
TI  - A sharp cadherin-6 gene expression boundary in the developing mouse cortical
      plate demarcates the future functional areal border.
AB  - The mammalian cerebral cortex can be tangentially subdivided into tens of
      functional areas with distinct cyto-architectures and neural circuitries;
      however, it remains elusive how these areal borders are genetically elaborated
      during development. Here we establish original bacterial artificial chromosome
      transgenic mouse lines that specifically recapitulate cadherin-6 (Cdh6) mRNA
      expression profiles in the layer IV of the somatosensory cortex and by detailing
      their cortical development, we show that a sharp Cdh6 gene expression boundary is
      formed at a mediolateral coordinate along the cortical layer IV as early as the
      postnatal day 5 (P5). By further applying mouse genetics that allows rigid cell
      fate tracing with CreERT2 expression, it is demonstrated that the Cdh6 gene
      expression boundary set at around P4 eventually demarcates the areal border
      between the somatosensory barrel and limb field at P20. In the P6 cortical cell
      pellet culture system, neurons with Cdh6 expression preferentially form
      aggregates in a manner dependent on Ca(2+) and electroporation-based Cdh6
      overexpression limited to the postnatal stages perturbs area-specific cell
      organization in the barrel field. These results suggest that Cdh6 expression in
      the nascent cortical plate may serve solidification of the protomap for cortical
      functional areas. 

PMID- 22875868
TI  - Independence of early speech processing from word meaning.
AB  - We combined magnetoencephalography (MEG) with magnetic resonance imaging and
      electrocorticography to separate in anatomy and latency 2 fundamental stages
      underlying speech comprehension. The first acoustic-phonetic stage is selective
      for words relative to control stimuli individually matched on acoustic
      properties. It begins ~60 ms after stimulus onset and is localized to middle
      superior temporal cortex. It was replicated in another experiment, but is
      strongly dissociated from the response to tones in the same subjects. Within the
      same task, semantic priming of the same words by a related picture modulates
      cortical processing in a broader network, but this does not begin until ~217 ms.
      The earlier onset of acoustic-phonetic processing compared with lexico-semantic
      modulation was significant in each individual subject. The MEG source estimates
      were confirmed with intracranial local field potential and high gamma power
      responses acquired in 2 additional subjects performing the same task. These
      recordings further identified sites within superior temporal cortex that
      responded only to the acoustic-phonetic contrast at short latencies, or the
      lexico-semantic at long. The independence of the early acoustic-phonetic response
      from semantic context suggests a limited role for lexical feedback in early
      speech perception. 

PMID- 22875869
TI  - CD4+ CD25+High Foxp3+ regulatory T cells, B lymphocytes, and T lymphocytes in
      patients with acute ITP in Assiut Children Hospital.
AB  - We aimed to examine the levels of lymphocyte subsets and regulatory T cells in
      patients with newly diagnosed immune thrombocytopenia (ITP) and their correlation
      with the course of ITP. The study included 40 pediatric patients with acute ITP
      and 30 controls. Lymphocytes and regulatory T cells were analyzed by flow
      cytometry. The percentages of CD19(+) and CD8(+) cells were significantly
      increased while that of CD4(+) cells and CD4(+)/CD8(+) ratio were significantly
      decreased. The percentages of CD4(+)CD25(+High) and CD4(+)CD25(+High) forkhead
      box protein 3 (Foxp3(+)) cells and the expression of Foxp3(+) in
      CD4(+)CD25(+High) cells were significantly decreased in patients. Age, platelet
      count, and mean platelet volume (MPV) in patients with brief duration of
      thrombocytopenia were significantly decreased than in those with prolonged
      duration. The percentages of CD8(+), CD4(+)CD25(+High), and CD4(+)CD25(+High)
      Foxp3(+) were significantly increased in patients with brief duration. Age,
      platelet count and MPV, and CD8+ cells had prognostic significance.
      CD4(+)CD25(+High) Foxp(+) T cells may be a helpful prognostic marker in children
      with acute ITP. 

PMID- 22875876
TI  - Hepatitis B and C virus infection among 1.2 million persons with access to care:
      factors associated with testing and infection prevalence.
AB  - BACKGROUND: Little is known about viral hepatitis testing and infection
      prevalence among persons in private healthcare organizations (HCOs) in the United
      States. METHODS: To determine the frequency of and characteristics associated
      with viral hepatitis testing and infection prevalence among adults with access to
      care, we conducted an observational cohort study among 1.25 million adults from 4
      US HCOs and included persons with >=1 clinical encounter during 2006-2008 and
      >=12 months of continuous follow-up before 2009. We compared the number of
      infections identified with the number expected based on adjusted data from the
      National Health and Nutrition Examination Survey (NHANES). RESULTS: Of 866,886
      persons without a previous hepatitis B virus (HBV) diagnosis, 18.8% were tested
      for HBV infection, of whom 1.4% tested positive; among 865,659 without a previous
      hepatitis C virus (HCV) diagnosis, 12.7% were tested, of whom 5.5% tested
      positive. Less than half of those with >=2 abnormal alanine aminotransferase
      (ALT) levels were subsequently tested for HBV or HCV. When tested, Asians
      (adjusted odds ratio [aOR] 6.33 relative to whites) were most likely HBV
      infected, whereas those aged 50-59 years were most likely HCV infected (aOR 6.04,
      relative to age <30 years). Based on estimates from NHANES, nearly one-half of
      HCV and one-fifth of HBV infections in this population were not identified.
      CONCLUSIONS: Even in this population with access to care and lengthy follow-up,
      only a fraction of expected viral hepatitis infections were identified. Abnormal
      ALT levels often but not consistently triggered testing. These findings have
      implications for the identification and care of 4-5 million US residents with HBV
      and HCV infection.

PMID- 22875877
TI  - Headaches that kill: a retrospective study of incidence, etiology and clinical
      features in cases of sudden death.
AB  - OBJECTIVE: The study objective was to analyze cases of sudden death that
      presented to the National Deptartment of Clinical Neurosciences, Ireland, over a
      10-year period (1997-2006) where headache was the presenting symptom. BACKGROUND:
      Headache is a common yet challenging presentation in clinical neurology. In the
      vast majority of cases, the cause is trivial and reversible-however, in a few
      patients it may be indicative of a more sinister intracranial process.
      Recognizing associated "red flag" features and identifying possible life
      threatening causes are crucial in ensuring prompt and appropriate intervention.
      DESIGN/METHODS: A retrospective study/database of all autopsy cases presenting to
      the Neuropathology Department in Beaumont Hospital, Dublin, was carried out for
      the period 1997-2006. Cases were selected with headache as the presenting
      clinical feature. Traumatic head injuries or known central nervous system (CNS)
      disorders were excluded. Autopsy and medical reports were reviewed to identify
      associated red flag features at initial presentation according to the
      International Classification of Headache Diseases, second edition (ICHD-II)
      criteria. RESULTS: Fifty-five autopsy cases out of a total of 499 complying with
      selection criteria were reviewed. Over the 10-year-study period, the number of
      cases of fatal headaches over time were negatively correlated. The most commonly
      associated red flag symptoms included age over 50: loss of consciousness and
      collapse, and worst/thunderclap character of headache. Cause of death at autopsy
      comprised vascular events 60.4% (N = 29), primary brain tumours/cysts 16.7% (N =
      8) and meningitis 6.25% (N = 3). Aneurysms accounted for the majority of vascular
      cases 22.9% (N = 11), with loss of consciousness, occipital headache, neck pain
      and a focal neurological deficit seen more commonly in this subset of cases.
      CONCLUSIONS: Sudden-onset headache is a common and often alarming presentation.
      The majority of cases are of a benign nature; however, a small proportion may be
      indicative of a catastrophic etiology. Documenting "red flags" on initial
      presentation is crucial to acutely identify and treat those at highest risk. The
      results demonstrate an improving trend among clinicians in recognizing and
      initiating appropriate interventions in these patients, and highlights particular
      red flag features common in cases of fatal headaches.

PMID- 22875878
TI  - Chronic headaches and insomnia: working toward a biobehavioral model.
AB  - BACKGROUND: Sleep disturbances are consistently associated with chronic
      headaches, yet the mechanisms underlying this relationship remain unclear. One
      potential barrier to generating new hypotheses is the lack of synthesis between
      models of headache and models of sleep. The goal of this paper is to present a
      perspective on the chronification of migraine and tension-type headaches based
      upon conceptual models used in sleep research. METHODS: We provide a critical
      review of the literature on sleep and headache, highlighting the limitations in
      sleep methodology. Models of sleep physiology and insomnia are discussed, along
      with the potential implications for the chronification of migraine and tension
      type headache. In addition, we propose a biobehavioral model that describes the
      interaction between behaviors related to coping with headache, the impact of
      these behaviors on insomnia and sleep physiology and the downstream propensity
      for future headache attacks. CONCLUSIONS: We hope that this perspective will
      stimulate interdisciplinary activity toward uncovering the pathway for more
      effective interventions for chronic headache patients.

PMID- 22875879
TI  - Migraine, weight gain and the risk of becoming overweight and obese: a
      prospective cohort study.
AB  - BACKGROUND: Some cross-sectional studies have suggested an association between
      migraine and increased body weight. However, prospective data on the association
      are lacking. METHODS: We conducted a prospective cohort study among 19,162
      participants in the Women's Health Study who had a body mass index (BMI) of 18.5-
      <25 kg/m(2) at baseline. Migraine was self-reported by standardized
      questionnaires. Main outcome measures were incident overweight (BMI >= 25
      kg/m(2)), incident obesity (BMI >= 30 kg/m(2)) and mean weight change. Age- and
      multivariable-adjusted hazard ratios (HRs) were calculated for the association
      between migraine and incident overweight and obesity. Differences in weight
      change were evaluated by analysis of covariance (ANCOVA). RESULTS: A total of
      3,483 (18.2%) women reported any migraine history. After 12.9 years of follow-up,
      7916 incident overweight and 730 incident obesity cases occurred. Migraineurs had
      multivariable-adjusted HRs (95% confidence interval) of 1.11 (1.05-1.17) for
      becoming overweight and 1.00 (0.83-1.19) for becoming obese. These associations
      remained stable after censoring for chronic diseases and were similar according
      to migraine aura status. Multivariable-adjusted mean weight change from baseline
      to the end of study was +4.7 kg for migraineurs and +4.4 kg for women without
      migraine (p = 0.02). CONCLUSION: Results of this large prospective study of
      middle-aged women do not indicate a consistent association between migraine and
      incident overweight, obesity or relevant weight gain.

PMID- 22875880
TI  - The analysis of allodynia in patients with idiopathic intracranial hypertension.
AB  - OBJECTIVES: Allodynia is frequently associated with migraine and other primary
      headaches. Our aim was to investigate the presence of allodynia and related
      features in idiopathic intracranial hypertension (IIH), which is a disabling
      secondary headache disorder. METHODS: We included 46 IIH patients and analyzed
      their clinical and laboratory findings retrospectively. Allodynia was assessed
      using the validated 12-item allodynia symptom checklist (ASC-12), in addition to
      examining pressure (with von Frey filaments) and brush allodynia. RESULTS:
      Allodynia was detected in 23 (50%) of IIH patients with ASC-12 and/or
      instrumental testing. The most commonly reported location was unilateral V1
      distribution. The allodynic symptom profile was similar but milder when compared
      to 143 migraineurs with ASC-12. Only the aggravation of headache with physical
      activity emerged as a significant variable associated with allodynia in IIH.
      Among allodynic patients, only eight had previous migraine diagnosis. After onset
      of IIH, 20 patients reported migraine-like headache, while only three reported
      non-migrainous headache. In contrast, 13 of 23 non-allodynic IIH patients had non
      migrainous headache features (p = 0.0045). CONCLUSION: Half of the IIH patients
      reported allodynia, and these allodynic patients had mostly migraine-like
      headache profiles. Our study suggested that IIH may trigger some common
      mechanisms with migraine in pain pathways causing allodynia.

PMID- 22875881
TI  - Seven years practicing neurology and headache medicine in Myanmar (Burma)--an
      experience with a surprise.

PMID- 22875882
TI  - The immune theory of psychiatric diseases: a key role for activated microglia and
      circulating monocytes.
AB  - This review describes a key role for mononuclear phagocytes in the pathogenesis
      of major psychiatric disorders. There is accumulating evidence for activation of
      microglia (histopathology and PET scans) and circulating monocytes (enhanced gene
      expression of immune genes, an overproduction of monocyte/macrophage-related
      cytokines) in patients with bipolar disorder, major depressive disorder, and
      schizophrenia. These data are strengthened by observations in animal models, such
      as the MIA models, the chronic stress models, and the NOD mouse model. In these
      animal models of depressive-, anxiety-, and schizophrenia-like behavior, similar
      activations of microglia and circulating monocytes can be found. These animal
      models also make in-depth pathogenic studies possible and show that microglia
      activation impacts neuronal development and function in brain areas congruent
      with the altered depressive and schizophrenia-like behaviors.

PMID- 22875883
TI  - Ultrasmall superparamagnetic particles of iron oxide in patients with acute
      myocardial infarction: early clinical experience.
AB  - BACKGROUND: Inflammation following acute myocardial infarction (MI) has
      detrimental effects on reperfusion, myocardial remodelling, and ventricular
      function. Magnetic resonance imaging using ultrasmall superparamagnetic particles
      of iron oxide can detect cellular inflammation in tissues, and we therefore
      explored their role in acute MI in humans. METHODS AND RESULTS: Sixteen patients
      with acute ST-segment elevation MI were recruited to undergo 3 sequential
      magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours
      following no infusion (controls; n=6) or intravenous infusion of ultrasmall
      superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted
      multigradient-echo sequences were acquired and R2* values were calculated for
      specific regions of interest. In the control group, R2* values remained constant
      in all tissues across all scans with excellent repeatability (bias of -0.208 s(
      1), coefficient of repeatability of 26.96 s(-1); intraclass coefficient 0.989).
      Consistent with uptake by the reticuloendothelial system, R2* value increased in
      the liver (84+/-49.5 to 319+/-70.0 s(-1); P<0.001) but was unchanged in skeletal
      muscle (54+/-8.4 to 67.0+/-9.5 s(-1); P>0.05) 24 hours after administration of
      ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct,
      R2* value increased from 41.0+/-12.0 s(-1) (baseline) to 155+/-45.0 s(-1)
      (P<0.001) and 124+/-35.0 s(-1) (P<0.05) at 24 and 48 hours, respectively. A
      similar but lower magnitude response was seen in the remote myocardium, where it
      increased from 39+/-3.2 s(-1) (baseline) to 80+/-14.9 s(-1) (P<0.001) and 67.0+/
      15.7 s(-1) (P<0.05) at 24 and 48 hours, respectively. CONCLUSIONS: Following
      acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs
      with the infarcted and remote myocardium. This technique holds major promise as a
      potential method for assessing cellular myocardial inflammation and left
      ventricular remodelling, which may have a range of applications in patients with
      MI and other inflammatory cardiac conditions.

PMID- 22875884
TI  - Prognostic value of right ventricular longitudinal peak systolic strain in
      patients with pulmonary hypertension.
AB  - BACKGROUND: Right ventricular (RV) function is an important prognostic marker in
      patients with pulmonary hypertension. The present evaluation assessed the
      prognostic value of RV longitudinal peak systolic strain (LPSS) in patients with
      pulmonary hypertension. METHODS AND RESULTS: A total of 150 patients with
      pulmonary hypertension of different etiologies (mean age, 59+/-15 years; 37.3%
      male) were evaluated. RV fractional area change and tricuspid annular plane
      systolic excursion index were evaluated with 2-dimensional echocardiography. RV
      LPSS was assessed with speckle-tracking echocardiography. The patient population
      was categorized according to a RV LPSS value of -19%. Among several clinical and
      echocardiographic parameters, the significant determinants of all-cause mortality
      were evaluated. There were no significant differences in age, sex, pulmonary
      hypertension cause and left ventricular ejection fraction between patients with
      RV LPSS <-19% and patients with RV LPSS >=-19%. However, patients with RV LPSS >=
      19% had significantly worse New York Heart Association functional class (2.7+/
      0.6 versus 2.3+/-0.8; P=0.003) and lower tricuspid annular plane systolic
      excursion (16+/-4 mm versus 18+/-3 mm; P<0.001) than their counterparts. During a
      median follow-up of 2.6 years, 37 patients died. RV LPSS was a significant
      determinant of all-cause mortality (HR, 3.40; 95% CI, 1.19-9.72; P=0.02).
      CONCLUSIONS: In patients with pulmonary hypertension, RV LPSS is significantly
      associated with all-cause mortality. RV LPSS may be a valuable parameter for risk
      stratification of these patients. Future studies are needed to confirm these
      results in the pulmonary hypertension subgroups.

PMID- 22875885
TI  - Development of rapid serotype-specific PCR assays for eight serotypes of
      Streptococcus suis.
AB  - Streptococcus suis is an emerging zoonotic pathogen causing severe infections in
      pigs and humans. Thirty-three serotypes of S. suis have been identified using
      serum agglutination. The capsular polysaccharides synthesis (cps) locus is
      usually conserved among different strains of the same serotype. The cps loci of
      15 serotypes have been sequenced, while the loci of the other serotypes remain
      unknown. In the present study, two to six serotype-specific genes of each of
      eight serotypes, i.e., serotypes 3, 4, 5, 8, 10, 19, 23, and 25, were identified
      using cross-hybridization with 93 nucleic acid probes specific to genes in the
      cps locus, and serotype-specific PCR assays for rapid and sensitive detection of
      the eight serotypes were then developed. The PCR typing results of the 148
      serologically typeable isolates were completely consistent with agglutination
      results. Furthermore, some autoagglutinating, acapsular, and multiagglutinating
      strains which could not be differentiated by traditional serum agglutination
      assays were positive in the PCR assays. Use of the PCR assays with clinical
      tonsillar specimens showed that the assays are sensitive and able to identify
      samples with autoagglutinating isolates. To our knowledge, this is the first
      study to identify the serotype-specific genes of the eight Streptococcus suis
      serotypes and develop rapid and sensitive PCR assays for the eight serotypes
      which can be identified only by serum agglutination.

PMID- 22875886
TI  - Enrichment of multilocus sequence typing clade 1 with oral Candida albicans
      isolates in patients with untreated periodontitis.
AB  - This study investigated the prevalence and cell density of Candida species in
      periodontal pockets, healthy subgingival sites, and oral rinse samples of
      patients with untreated periodontitis. Twenty-one periodontitis patients
      underwent sampling at two periodontitis sites, and 19/21 of these patients
      underwent sampling at one periodontally healthy site. Both paper point and
      curette sampling techniques were employed. The periodontitis patients and 50
      healthy subjects were also sampled by oral rinse. Candida isolates were recovered
      on CHROMagar Candida medium, and representative isolates were identified. Candida
      spp. were recovered from 10/21 (46.7%) periodontitis patients and from 16/50
      (32%) healthy subjects. C. albicans predominated in both groups and was recovered
      from all Candida-positive subjects. Candida-positive periodontitis patients
      yielded Candida from periodontal pockets with average densities of 3,528 and
      3,910 CFU/sample from curette and paper point samples, respectively, and 1,536
      CFU/ml from oral rinse samples. The majority (18/19) of the healthy sites sampled
      from periodontitis patients were Candida negative. The 16 Candida-positive
      healthy subjects yielded an average of 279 CFU/ml from oral rinse samples. C.
      albicans isolates were investigated by multilocus sequence typing (MLST) to
      determine if specific clonal groups were associated with periodontitis. MLST
      analysis of 31 C. albicans isolates from periodontitis patients yielded 19
      sequence types (STs), 13 of which were novel. Eleven STs belonged to MLST clade
      1. In contrast, 16 C. albicans isolates from separate healthy subjects belonged
      to 16 STs, with 4 isolates belonging to clade 1. The distributions of STs between
      both groups were significantly different (P = 0.04) and indicated an enrichment
      of C. albicans isolates in periodontal pockets, which warrants a larger study.

PMID- 22875887
TI  - Microbiological applications of high-resolution melting analysis.
AB  - High-resolution melting (HRM) analysis uses real-time PCR instrumentation to
      interrogate DNA sequence variation and is a low-cost, single-step, closed-tube
      method. Here we describe HRM technology and provide examples of varied clinical
      microbiological applications to highlight the strengths and limitations of HRM
      analysis.

PMID- 22875888
TI  - Identification of blood culture isolates directly from positive blood cultures by
      use of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry and a commercial extraction system: analysis of performance, cost,
      and turnaround time.
AB  - Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass
      spectrometry represents a revolution in the rapid identification of bacterial and
      fungal pathogens in the clinical microbiology laboratory. Recently, MALDI-TOF has
      been applied directly to positive blood culture bottles for the rapid
      identification of pathogens, leading to reductions in turnaround time and
      potentially beneficial patient impacts. The development of a commercially
      available extraction kit (Bruker Sepsityper) for use with the Bruker MALDI
      BioTyper has facilitated the processing required for identification of pathogens
      directly from positive from blood cultures. We report the results of an
      evaluation of the accuracy, cost, and turnaround time of this method for 61
      positive monomicrobial and 2 polymicrobial cultures representing 26 species. The
      Bruker MALDI BioTyper with the Sepsityper gave a valid (score, >1.7)
      identification for 85.2% of positive blood cultures with no misidentifications.
      The mean reduction in turnaround time to identification was 34.3 h (P < 0.0001)
      in the ideal situation where MALDI-TOF was used for all blood cultures and 26.5 h
      in a more practical setting where conventional identification or identification
      from subcultures was required for isolates that could not be directly identified
      by MALDI-TOF. Implementation of a MALDI-TOF-based identification system for
      direct identification of pathogens from blood cultures is expected to be
      associated with a marginal increase in operating costs for most laboratories.
      However, the use of MALDI-TOF for direct identification is accurate and should
      result in reduced turnaround time to identification.

PMID- 22875889
TI  - Species identification and antifungal susceptibility testing of Candida
      bloodstream isolates from population-based surveillance studies in two U.S.
      cities from 2008 to 2011.
AB  - Between 2008 and 2011, population-based candidemia surveillance was conducted in
      Atlanta, GA, and Baltimore, MD. Surveillance had been previously performed in
      Atlanta in 1992 to 1993 and in Baltimore in 1998 to 2000, making this the first
      population-based candidemia surveillance conducted over multiple time points in
      the United States. From 2,675 identified cases of candidemia in the current
      surveillance, 2,329 Candida isolates were collected. Candida albicans no longer
      comprised the majority of isolates but remained the most frequently isolated
      species (38%), followed by Candida glabrata (29%), Candida parapsilosis (17%),
      and Candida tropicalis (10%). The species distribution has changed over time; in
      both Atlanta and Baltimore the proportion of C. albicans isolates decreased, and
      the proportion of C. glabrata isolates increased, while the proportion of C.
      parapsilosis isolates increased in Baltimore only. There were 98 multispecies
      episodes, with C. albicans and C. glabrata the most frequently encountered
      combination. The new species-specific CLSI Candida MIC breakpoints were applied
      to these data. With the exception of C. glabrata (11.9% resistant), resistance to
      fluconazole was very low (2.3% of isolates for C. albicans, 6.2% for C.
      tropicalis, and 4.1% for C. parapsilosis). There was no change in the proportion
      of fluconazole resistance between surveillance periods. Overall echinocandin
      resistance was low (1% of isolates) but was higher for C. glabrata isolates,
      ranging from 2.1% isolates resistant to caspofungin in Baltimore to 3.1% isolates
      resistant to anidulafungin in Atlanta. Given the increase at both sites and the
      higher echinocandin resistance, C. glabrata should be closely monitored in future
      surveillance.

PMID- 22875890
TI  - Buruli ulcer disease in travelers and differentiation of Mycobacterium ulcerans
      strains from northern Australia.
AB  - Buruli ulcer (BU) is a necrotizing infection of skin and soft tissue caused by
      Mycobacterium ulcerans. In Australia, most cases of BU are linked to temperate,
      coastal Victoria and tropical, northern Queensland, and strains from these
      regions are distinguishable by variable-number tandem repeat (VNTR) typing. We
      present an epidemiological investigation of five patients found to have been
      infected during interstate travel and describe two nucleotide polymorphisms that
      differentiate M. ulcerans strains from northern Australia.

PMID- 22875891
TI  - Microsatellite genotyping clarified conspicuous accumulation of Candida
      parapsilosis at a cardiothoracic surgery intensive care unit.
AB  - Candida parapsilosis has become a significant cause of invasive fungal infections
      in seriously ill patients. Nosocomial outbreaks through direct and indirect
      contact have been described. The aim of this study was the molecular
      characterization of what appeared to be an ongoing C. parapsilosis outbreak at
      the cardiothoracic intensive care unit of the University Hospital of Vienna
      between January 2007 and December 2008. Using two different molecular typing
      methods-automated repetitive sequence-based PCR (DiversiLab; bioMerieux) and
      microsatellite genotyping-we investigated the genetic relationship of 99 C.
      parapsilosis isolates. Eighty-three isolates originated from the cardiothoracic
      intensive care unit, while 16 isolates were random control isolates from other
      intensive care units and a different Austrian hospital. The 99 C. parapsilosis
      isolates analyzed by repetitive-element PCR all showed identical genotypes,
      suggesting an ongoing outbreak. In contrast, microsatellite genotyping showed a
      total of 56 different genotypes. Two major genotypes were observed in 10 and 15
      isolates, respectively, whereas another 13 genotypes were observed in 2 to 4
      isolates each. Forty-one genotypes were observed only once. Closely related
      genotypes that differed in only a single microsatellite marker were grouped into
      clonal complexes. When it comes to C. parapsilosis, microsatellite genotyping is
      a more discriminative method than repetitive-element PCR genotyping to
      investigate outbreaks.

PMID- 22875892
TI  - Type-specific identification of anogenital herpes simplex virus infections by use
      of a commercially available nucleic acid amplification test.
AB  - Herpes infections are among the most common sexually transmitted infections
      (STI), but diagnostic methods for genital herpes have not kept pace with the
      movement toward molecular testing. Here, we describe an FDA-approved molecular
      assay that identifies and types herpes simplex virus (HSV) infections for use in
      routine clinical settings. Paired samples from anogenital lesions were tested
      using the BD ProbeTec HSV Q(x) (HSVQ(x)) system, HSV culture and, a laboratory
      developed PCR assay. Family planning, obstetrics/gynecology (OB/GYN), or sexually
      transmitted disease (STD) clinics in the United States served as recruitment
      sites. Sensitivity and specificity estimates, head-to-head comparisons, measures
      of agreement, and latent-class analyses were performed to provide robust
      estimates of performance. A total of 508 participants (174 men and 334 women)
      with anogenital lesions were included; 260 HSV-2 and 73 HSV-1 infections were
      identified. No differences in test performance based on gender, clinic type,
      location of the lesion, or type of lesion were observed. The sensitivity of HSV-2
      detection ranged from 98.4 to 100% depending on the analytical approach, while
      the specificity ranged from 80.6%, compared to the less sensitive culture method,
      to 97.0%, compared to PCR. For HSV-1, the sensitivity and specificity ranges were
      96.7 to 100% and 95.1 to 99.4%, respectively. This assay may improve our ability
      to accurately diagnose anogenital lesions due to herpes infection.

PMID- 22875893
TI  - Comparison of the GenMark Diagnostics eSensor respiratory viral panel to real
      time PCR for detection of respiratory viruses in children.
AB  - A novel eSensor respiratory viral panel (eSensor RVP) multiplexed nucleic acid
      amplification test (GenMark Diagnostics, Inc., Carlsbad, CA) was compared to
      laboratory-developed real-time PCR assays for the detection of various
      respiratory viruses. A total of 250 frozen archived pediatric respiratory
      specimens previously characterized as either negative or positive for one or more
      viruses by real-time PCR were examined using the eSensor RVP. Overall agreement
      between the eSensor RVP and corresponding real-time PCR assays for shared
      analytes was 99.2% (kappa = 0.96 [95% confidence interval {CI}, 0.94 to 0.98]).
      The combined positive percent agreement was 95.4% (95% CI, 92.5 to 97.3); the
      negative percent agreement was 99.7% (95% CI, 99.4 to 99.8). The mean real-time
      PCR threshold cycle (C(T)) value for specimens with discordant results was 39.73
      (95% CI, 38.03 to 41.43). Detection of coinfections and correct identification of
      influenza A virus subtypes were comparable between methods. Of note, the eSensor
      RVP rhinovirus assay was found to be more sensitive and specific than the
      corresponding rhinovirus real-time PCR. In contrast, the eSensor RVP adenovirus
      B, C, and E assays demonstrated some cross-reactivity when tested against known
      adenovirus serotypes representing groups A through F. The eSensor RVP is robust
      and relatively easy to perform, it involves a unique biosensor technology for
      target detection, and its multiplexed design allows for efficient and
      simultaneous interrogation of a single specimen for multiple viruses. Potential
      drawbacks include a slower turnaround time and the need to manipulate amplified
      product during the protocol, increasing the possibility of contamination.

PMID- 22875894
TI  - Nearly constant shedding of diverse enteric viruses by two healthy infants.
AB  - Stool samples from two healthy infant siblings collected at about weekly
      intervals during their first year of life were analyzed by PCR for 15 different
      enteric viral genera. Adenovirus, Aichi virus, Anellovirus, Astrovirus,
      Bocavirus, Enterovirus, Parechovirus, Picobirnavirus, and Rotavirus were
      detected. Not detected were Coronavirus, Cardiovirus, Cosavirus, Salivirus,
      Sapovirus, and Norovirus. Long-term virus shedding, lasting from one to 12
      months, was observed for adenoviruses, anelloviruses, bocaviruses, enteroviruses,
      parechoviruses, and picobirnaviruses. Repeated administration of oral poliovirus
      vaccine resulted in progressively shorter periods of poliovirus detection. Four
      nonpolio enterovirus genotypes were also detected. An average of 1.8 distinct
      human viruses were found per time point. Ninety-two percent (66/72) of the fecal
      samples tested contained one to five different human viruses. Two British
      siblings in the mid-1980s showed nearly constant fecal viral shedding. Our
      results demonstrate that frequent enteric infections with diverse viruses occur
      during early childhood in the absence of severe clinical symptoms.

PMID- 22875895
TI  - Rapid and easy identification of capsular serotypes of Streptococcus pneumoniae
      by use of fragment analysis by automated fluorescence-based capillary
      electrophoresis.
AB  - The purpose of this study was to develop a high-throughput method for the
      identification of pneumococcal capsular types. Multiplex PCR combined with
      fragment analysis and automated fluorescent capillary electrophoresis (FAF-mPCR)
      was utilized. FAF-mPCR was composed of only 3 PCRs for the specific detection of
      serotypes 1, 2, 3, 4, 5, 6A/6B, 6C, 7F/7A, 7C/(7B/40), 8, 9V/9A, 9N/9L, 10A,
      10F/(10C/33C), 11A/11D/11F, 12F/(12A/44/46), 13, 14, 15A/15F, 15B/15C, 16F, 17F,
      18/(18A/18B/18C/18F), 19A, 19F, 20, 21, 22F/22A, 23A, 23B, 23F, 24/(24A/24B/24F),
      31, 33F/(33A/37), 34, 35A/(35C/42), 35B, 35F/47F, 38/25F, and 39. In order to
      evaluate the assay, all invasive pneumococcal isolates (n = 394) characterized at
      Hospital Sant Joan de Deu, Barcelona, Spain, from July 2010 to July 2011 were
      included in this study. The Wallace coefficient was used to evaluate the overall
      agreement between two typing methods (Quellung reaction versus FAF-mPCR). A high
      concordance with Quellung was found: 97.2% (383/394) of samples. The Wallace
      coefficient was 0.981 (range, 0.965 to 0.997). Only 11 results were discordant
      with the Quellung reaction. However, latex reaction and Quellung results of the
      second reference laboratory agreed with FAF-mPCR for 9 of these 11 strains (82%).
      Therefore, we considered that only 2 of 394 strains (0.5%) were not properly
      characterized by the new assay. The automation of the process allowed the typing
      of 30 isolates in a few hours with a lower cost than that of the Quellung
      reaction. These results indicate that FAF-mPCR is a good method to determine the
      capsular serotype of Streptococcus pneumoniae.

PMID- 22875896
TI  - Clonal distribution of common pneumococcal serotypes not included in the 7-valent
      conjugate vaccine (PCV7): marked differences between two ethnic populations in
      southern Israel.
AB  - This study aimed to compare the clonal distribution of common pneumococcal
      strains not included in the 7-valent pneumococcal conjugate vaccine (PCV7) that
      were isolated from cases of acute otitis media (AOM) and invasive pneumococcal
      disease (IPD) in two distinct ethnic populations in southern Israel during the
      decade (1999 to 2008) preceding PCV7 implementation. Isolates recovered from
      Jewish and Bedouin children <5 years old were characterized by antibiotic
      resistance and molecular epidemiology using pulsed-field gel electrophoresis and
      multilocus sequence typing. Of 5,236 AOM and 425 IPD isolates, 43% and 57% were
      from Jewish and Bedouin children, respectively. PCV7 accounted for 54% and 45% of
      the AOM and IPD episodes, respectively. Eleven major non-PCV7 serotypes (1, 3, 5,
      6A, 7F, 12F, 15B/C, 19A, 21, 33F, and 35B) constituted 31% and 42% of the AOM and
      IPD episodes, respectively. The clonal distributions of the 11 non-PCV7 serotypes
      and their antibiotic susceptibilities were significantly different among the two
      ethnic populations in both the AOM and IPD groups. About half of the AOM and IPD
      cases resulted from non-PCV7 pneumococci, even before PCV7 implementation. The
      significant differences between the two ethnic populations suggest that lifestyle
      and microenvironment are major determinants in the clonal distribution of disease
      causing pneumococci. Post-PCV7 surveillance is important in understanding non
      PCV7 clonal expansion in the two distinct populations.

PMID- 22875897
TI  - A PCR-based intergenic spacer region-capillary gel electrophoresis typing method
      for identification and subtyping of Nocardia species.
AB  - While 16S rRNA sequence-based identification of Nocardia species has become the
      gold standard, it is not without its limitations. We evaluated a novel approach
      encompassing the amplification of the Nocardia 16S-23S rRNA intergenic spacer
      (IGS) region followed by fragment analysis by capillary gel electrophoresis (CGE)
      of the amplified product for species identification of Nocardia. One hundred
      forty-five Nocardia isolates (19 species) and four non-Nocardia aerobic
      actinomycetes were studied. Reproducibility testing was performed in a subset
      (21%) of isolates. Ninety-five different electropherograms were identified, with
      heterogeneity within species being a general observation. Among common Nocardia
      species (e.g., Nocardia cyriacigeorgica, N. nova, N. farcinica), 2 or 3 dominant
      electropherogram subgroups were typical. While only a minority (8/19; 42%) of the
      different Nocardia species contained isolates displaying unique fragment sizes
      that were predictive of a particular species, virtually all isolates (142/145;
      98%) could be assigned to the correct species using IGS-CGE typing based on the
      number and size of amplified fragments. The median number of fragments for each
      isolate was 2 (range, 1 to 5) with only a minority (17%) having a single fragment
      detected. The majority (93%) of amplified fragments were between 408 and 461 bp.
      The technique was also non-operator dependent, highly reproducible, and quicker
      and less expensive than 16S sequencing. In summary, PCR-based IGS-CGE typing is
      relatively simple, accurate, reproducible, and cost-effective and offers a
      potential alternative to 16S rRNA sequencing for identifying and subtyping
      Nocardia isolates.

PMID- 22875898
TI  - Visual detection of rpoB mutations in rifampin-resistant Mycobacterium
      tuberculosis strains by use of an asymmetrically split peroxidase DNAzyme.
AB  - Multidrug-resistant Mycobacterium tuberculosis is resistant to two first-line
      antituberculosis drugs, isoniazid and rifampin, resulting in the relapse of
      tuberculosis. M. tuberculosis grows very slowly, and thus traditional examination
      methods take time to test its drug resistance and cannot meet clinical needs. The
      use of a DNA probe makes it possible to test rifampin resistance.  We developed
      an asymmetrical split-assembly DNA peroxidase assay to detect drug-resistant
      mutation of rifampin-resistant M. tuberculosis in the rpoB gene rapidly and
      visibly. A new strategy was also designed to eliminate the adverse effects caused
      by the complicated secondary structure of the target DNA and to improve the
      efficiency of the probes. This detection system consists of five group
      detections, covers rifampin-resistant determination region of the rpoB gene, and
      tests 40 kinds of mutations, including the most common mutations at codons 531
      and 526. Every group detection or individual mutant allele detection can
      distinguish corresponding mutant DNA sequences from the wild-type DNA sequences.

PMID- 22875900
TI  - Transcorneal alternating current stimulation induces EEG "aftereffects" only in
      rats with an intact visual system but not after severe optic nerve damage.
AB  - Noninvasive alternating current stimulation can induce vision restoration in
      patients with chronic optic nerve damage and results in electroencephalogram
      (EEG) aftereffects. To better understand the mechanisms of action, we studied
      such EEG "aftereffects" of transcorneal alternating current stimulation (tACS) at
      the chronic posttraumatic state in rats. EEG baseline was recorded from visual
      cortex under ketamine/xylazine narcosis of healthy rats and rats with chronic
      severe optic nerve crush. One week later, both groups were again anesthetized and
      stimulated transcorneally twice for 12 min each time. tACS-induced changes were
      compared with baseline EEG. Over the course of 65 min narcosis baseline EEG
      revealed a shift from a dominant delta power to theta. This shift was
      significantly delayed in lesioned animals compared with healthy controls. tACS
      applied during the late narcosis stage in normal rats led to significantly
      increased theta power with a parallel shift of the dominating peak to higher
      frequency which outlasted the stimulation period by 15 min (aftereffects). EEG in
      lesioned rats was not significantly changed. In rodents, tACS can induce
      neuroplasticity as shown by EEG aftereffects that outlast the stimulation period.
      But this requires a minimal level of brain activation because aftereffects are
      not seen when tACS is applied during deep anesthesia and not when applied to
      animals after severe optic nerve damage. We conclude that tACS is only effective
      to induce cortical plasticity when the the retina can be excited.

PMID- 22875899
TI  - Head direction cell activity in the anterodorsal thalamus requires intact
      supragenual nuclei.
AB  - Neural activity in several limbic areas varies as a function of the animal's head
      direction (HD) in the horizontal plane. Lesions of the vestibular periphery
      abolish this HD cell signal, suggesting an essential role for vestibular
      afference in HD signal generation. The organization of brain stem pathways
      conveying vestibular information to the HD circuit is poorly understood; however,
      recent anatomical work has identified the supragenual nucleus (SGN) as a putative
      relay. To test this hypothesis, we made lesions of the SGN in rats and screened
      for HD cells in the anterodorsal thalamus. In animals with complete bilateral
      lesions, the overall number of HD cells was significantly reduced relative to
      control animals. In animals with unilateral lesions of the SGN, directional
      activity was present, but the preferred firing directions of these cells were
      unstable and less influenced by the rotation of an environmental landmark. In
      addition, we found that preferred directions displayed large directional shifts
      when animals foraged for food in a darkened environment and when they were
      navigating from a familiar environment to a novel one, suggesting that the SGN
      plays a critical role in projecting essential self-motion (idiothetic)
      information to the HD cell circuit.

PMID- 22875901
TI  - Pontine MU-opioid receptors mediate bradypnea caused by intravenous remifentanil
      infusions at clinically relevant concentrations in dogs.
AB  - Life-threatening side effects such as profound bradypnea or apnea and variable
      upper airway obstruction limit the use of opioids for analgesia. It is yet
      unclear which sites containing MU-opioid receptors (MUORs) within the intact in
      vivo mammalian respiratory control network are responsible. The purpose of this
      study was 1) to define the pontine region in which MUOR agonists produce
      bradypnea and 2) to determine whether antagonism of those MUORs reverses
      bradypnea produced by intravenous remifentanil (remi; 0.1-1.0 MUg.kg(-1).min(
      1)). The effects of microinjections of agonist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]
      enkephalin (DAMGO; 100 MUM) and antagonist naloxone (NAL; 100 MUM) into the
      dorsal rostral pons on the phrenic neurogram were studied in a decerebrate,
      vagotomized, ventilated, paralyzed canine preparation during hyperoxia. A 1-mm
      grid pattern of microinjections was used. The DAMGO-sensitive region extended
      from 5 to 7 mm lateral of midline and from 0 to 2 mm caudal of the inferior
      colliculus at a depth of 3-4 mm. During remi-induced bradypnea (~72% reduction in
      fictive breathing rate) NAL microinjections (~500 nl each) within the region
      defined by the DAMGO protocol were able to reverse bradypnea by 47% (SD 48.0%)
      per microinjection, with 13 of 84 microinjections producing complete reversal.
      Histological examination of fluorescent microsphere injections shows that the
      sensitive region corresponds to the parabrachial/Kolliker-Fuse complex.

PMID- 22875902
TI  - Dissociated mean and functional connectivity BOLD signals in visual cortex during
      eyes closed and fixation.
AB  - We investigated the effects of resting state type on blood oxygen level-dependent
      (BOLD) signal and functional connectivity in two paradigms: participants either
      alternated between fixation and eyes closed or maintained fixation or eyes closed
      throughout each scan. The BOLD signal and functional connectivity of lower and
      higher tiers of the visual cortical hierarchy were found to be differentially
      modulated during eyes closed versus fixation. Fixation was associated with
      greater mean BOLD signals in primary visual cortex and lower mean BOLD signals in
      extrastriate visual areas than periods of eyes closed. In addition, analysis of
      thalamocortical functional connectivity during scans in which participants
      maintained fixation showed synchronized BOLD fluctuations between those thalamic
      nuclei whose mean BOLD signal was systematically modulated during alternating
      epochs of eyes closed and fixation, primary visual cortex and the attention
      network, while during eyes closed negatively correlated fluctuations were seen
      between the same thalamic nuclei and extrastriate visual areas. Finally, in all
      visual areas the amplitude of spontaneous BOLD fluctuations was greater during
      eyes closed than during fixation. The dissociation between early and late tiers
      of visual cortex, which characterizes both mean and functionally connected
      components of the BOLD signal, may depend on the reorganization of
      thalamocortical networks. Since dissociated changes in local blood flow also
      characterize transitions between different stages of sleep and wakefulness (Braun
      AR, Balkin TJ, Wesenten NJ, Gwadry F, Carson RE, Varga M, Baldwin P, Belenky G,
      Herscovitch P. Science 279: 91-95, 1998), our results suggest that dissociated
      endogenous neural activity in primary and extrastriate cortex may represent a
      general aspect of brain function.

PMID- 22875903
TI  - Periodontal disease is significantly higher in non-smoking treatment-naive
      rheumatoid arthritis patients: results from a case-control study.
AB  - OBJECTIVE: To find the strength of association between periodontal disease (PD)
      and rheumatoid arthritis (RA) in non-smoking, disease modifying antirheumatic
      drug (DMARD)-naive RA patients in a case-control design. METHODS: Patients of RA
      (DMARD-naive, non-smokers) satisfying the American college of Rheumatology 1987
      criteria and healthy controls were included. PD was defined as present if the
      mean pocket depth (MPD) is >=3 mm. Demographic data and disease specific
      variables were recorded for RA patients and healthy controls. Titres of
      immunoglobulin M-rheumatoid factor (IgM-RF) and anticitrullinated peptide
      antibodies (ACPAs) were measured using ELISA. RESULTS: Patients with RA (n=91)
      had a 4.28 (CI 2.35 to 7.38) higher odds of PD (64.8% vs 28%, p<0.001) compared
      with healthy controls (n=93). The MPD was 3.61+/-1.22 mm in cases and 2.46+/-0.74
      mm in controls (p<0.001). IgM-RF titres (110.56+/-95.81 vs 66.53+/-70.29; p=0.02)
      and ACPA titres (753.05+/-1088.27 vs 145.15+/-613.16, p=0.001) were significantly
      higher in RA patients with PD than those without PD. The MPD positively
      correlated with titres of ACPAs in RA patients (r=0.24; p=0.02). CONCLUSIONS: PD
      is more frequent and severe in non-smoking DMARD-naive RA patients compared with
      healthy controls. PD in RA is associated with high titres of ACPAs.

PMID- 22875904
TI  - Asthma in Swedish children conceived by in vitro fertilisation.
AB  - OBJECTIVES: To investigate a proposed association between in vitro fertilisation
      (IVF) and child asthma. DESIGN: The risk for asthma after IVF was estimated as
      ORs using Mantel-Haenszel analysis. SETTING: The Swedish Medical Birth Register.
      PATIENTS: Of the 2 628 728 children born in 1982-2007 and surviving the perinatal
      period, 31 918 were conceived by IVF. Presence of asthma was defined as at least
      five prescriptions of antiasthmatic drugs during the period 1 July 2005-31
      December 2009 according to the Swedish Prescribed Drug Register (115 767
      children, 2323 of whom were born after IVF). RESULTS: A significantly increased
      risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28,
      95% CI 1.23 to 1.34), increasing the absolute risk from 4.4% to 5.6%. The risk
      increase for asthma was the same in boys and girls, in singletons and twins, and
      after caesarean section and vaginal delivery. The risk was higher for preterm
      than term singletons. For children with a low Apgar score, respiratory diagnoses,
      mechanical ventilation, continuous positive airway pressure or neonatal sepsis,
      the effect of IVF on asthma risk was low and statistically non-significant.
      Adjustment for length of involuntary childlessness eliminated the effect, and
      removal of infants whose mothers had used antiasthmatics in early pregnancy
      reduced the risk. CONCLUSIONS: This study verifies an association between IVF and
      asthma in children. This can be partly explained by neonatal morbidity and by
      maternal asthma acting as mediators, but the main risk factor is parental
      subfertility. The mechanism for this is unclear.

PMID- 22875905
TI  - Varicella postexposure prophylaxis in children with cancer: urgent need for a
      randomised controlled trial.

PMID- 22875906
TI  - Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead
      spermatozoa during epididymal transit in bovine.
AB  - Previously, we showed that epididymal sperm binding protein 1 (ELSPBP1)
      characterizes spermatozoa already dead before ejaculation in bovine. In this
      study, we investigated the presence of ELSPBP1 in bull genital tract as well as
      its acquisition by spermatozoa during epididymal transit. As assessed by real
      time RT-PCR, ELSPBP1 was highly expressed in the caput and the corpus epididymis
      but was present in lower expression levels in the testis and the cauda
      epididymis. Immunohistochemistry revealed the same expression pattern. However,
      Western blot on tissue homogenates showed some discrepancies, as ELSPBP1 was
      found in a comparable concentration all along the epididymis. This difference was
      due to the presence of ELSPBP1 in the epididymal fluid. In both caput and cauda
      epididymal fluid, ELSPBP1 was associated with the epididymosomes, small
      membranous vesicles secreted by epithelial cells of the epididymis and implicated
      in the transfer of proteins to spermatozoa. As assessed by immunocytometry,
      ELSPBP1 was found on a subset of dead spermatozoa in caput epididymis but was
      found on all dead spermatozoa in cauda epididymis. To assess ELSPBP1 acquisition
      by spermatozoa, caput epididymal spermatozoa were incubated with cauda
      epididymosomes under various conditions. ELSPBP1 detection by immunocytometry
      assay revealed that only spermatozoa already dead before incubation were
      receptive to ELSPBP1 transfer by epididymosomes. This receptivity was enhanced by
      the presence of zinc in the incubation medium. This specificity for a sperm
      subpopulation suggests that an underlying mechanism is involved and that ELSPBP1
      could be a tag for the recognition of dead spermatozoa during epididymal transit.

PMID- 22875907
TI  - DBA-lectin reactivity defines mouse uterine natural killer cell subsets with
      biased gene expression.
AB  - Endometrial decidualization, a process essential for blastocyst implantation in
      species with hemochorial placentation, is accompanied by an enormous but
      transient influx of natural killer (NK) cells. Mouse uterine NK (uNK) cell
      subsets have been defined by diameter and cytoplasmic granule number, reflecting
      stage of maturity, and by histochemical reactivity with Periodic Acid Schiff
      (PAS) reagent with or without co-reactivity with Dolichos biflorus agglutinin
      (DBA) lectin. We asked whether DBA- and DBA+ mouse uNK cells were equivalent
      using quantitative RT-PCR analyses of flow-separated, midpregnancy (Gestation Day
      [gd] 10) cells and immunohistochemistry. CD3E (CD3)-IL2RB (CD122)+DBA cells were
      identified as the dominant Ifng transcript source. Skewed IFNG production by uNK
      cell subsets was confirmed by analysis of uNK cells from eYFP-tagged IFNG
      reporter mice. In contrast, CD3E-IL2RB+DBA+ uNK cells expressed genes compatible
      with significantly greater potential for IL22 synthesis, angiogenesis, and
      participation in regulation mediated by the renin-angiotensin system (RAS). CD3E
      IL2RB+DBA+ cells were further divided into VEGFA+ and VEGFA- subsets. CD3E
      IL2RB+DBA+ uNK cells but not CD3E-IL2RB+DBA- uNK cells arose from circulating,
      bone marrow-derived progenitor cells by gd6. These findings indicate the
      heterogeneous nature of mouse uNK cells and suggest that studies using only DBA+
      uNK cells will give biased data that does not fully represent the uNK cell
      population.

PMID- 22875909
TI  - Impact of local endothelial challenge with cytomegalovirus or glycoprotein B on
      vasodilation in intact pressurized arteries from nonpregnant and pregnant mice.
AB  - Cytomegalovirus (CMV) infections are associated with vascular diseases in the
      human population. We have previously shown vascular dysfunction in systemic and
      uterine arteries dissected from nonpregnant (NP) mouse CMV (mCMV)-infected mice
      that was further impaired during late pregnancy (LP). CMV attachment alone
      through glycoprotein B (GB) can generate signals that impact vascular tone
      regulation. However, the contribution of direct virus interactions with
      endothelium to the vascular dysfunction we previously observed after in vivo mCMV
      infection is not known. We used a pressure myograph system to infuse GB or whole
      intact mCMV inside arteries dissected from uninfected mice and assessed
      vasodilation to methacholine infused inside pressurized arteries rather than
      applied abluminally. These results were compared to those observed after
      methacholine infusion into untreated arteries dissected from mCMV-infected mice.
      In mesenteric arteries, vasodilation to infused methacholine did not differ among
      treatments in NP or LP groups in contrast to previously published studies.
      However, increased vasoconstrictor activity was unmasked after blocking
      thromboxane receptors or prostaglandin production. Vasodilation in uterine
      arteries from uninfected NP mice to infused methacholine was increased by both GB
      and whole intact mCMV pretreatment. Untreated uterine arteries from mCMV-infected
      NP mice showed even greater vasodilation. There was no effect of GB or whole
      intact mCMV pretreatment in uterine arteries from uninfected LP mice, whereas
      vasodilation to infused methacholine was reduced in untreated uterine arteries
      from mCMV-infected LP mice. CMV exerts direct effects on vascular function which
      should be considered during viral reactivation leading to viremia and during GB
      based vaccine administration.

PMID- 22875908
TI  - Prenatal exposure to low doses of bisphenol A increases pituitary proliferation
      and gonadotroph number in female mice offspring at birth.
AB  - The pituitary gland is composed of hormone-producing cells essential for
      homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback
      in the adult and can have altered hormonal secretion from exposure to the
      endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in
      food and beverage containers, leading to widespread human exposure. Although
      prenatal exposure to BPA can impact reproductive function in the adult, the
      effects of BPA on the developing pituitary are unknown. We hypothesized that
      prenatal exposure to low doses of BPA impacts gonadotroph cell number or
      parameters of hormone synthesis. To test this, pregnant mice were administered
      0.5 MUg/kg/day of BPA, 50 MUg/kg/day of BPA, or vehicle beginning on Embryonic
      Day 10.5. At parturition, pituitaries from female offspring exposed in utero to
      either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels
      and immunohistochemistry. Coincidently, gonadotroph number also increased in
      treated females. However, we observed a dichotomy between mRNA levels of Lhb and
      Fshb. Female mice exposed to 0.5 MUg/kg/day BPA had increased mRNA levels of
      gonadotropins and the gonadotropin-receptor hormone (GNRH) receptor (Gnrhr),
      which mediates GNRH regulation of gonadotropin production and release. In
      contrast, mice treated with 50 MUg/kg/day of BPA had decreased gonadotropin mRNA
      levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph
      differentiation. No other pituitary hormones were altered on the day of birth in
      response to in utero BPA exposure, and male pituitaries showed no change in the
      parameters tested. Collectively, these results show that prenatal exposure to BPA
      affects pituitary gonadotroph development in females.

PMID- 22875910
TI  - Elite athletes travelling to international destinations >5 time zone differences
      from their home country have a 2-3-fold increased risk of illness.
AB  - BACKGROUND: Illness accounts for a significant proportion of consultations with a
      team physician travelling with elite athletes. OBJECTIVE: To determine if
      international travel increases the incidence of illness in rugby union players
      participating in a 16-week tournament. SETTING: 2010 Super 14 Rugby Union
      tournament. PARTICIPANTS: 259 elite rugby players from eight teams were followed
      daily over the 16-week competition period (22 676 player-days). ASSESSMENT: Team
      physicians completed a logbook detailing the daily squad size and illness in any
      player (system affected, final diagnosis, type and onset of symptoms,
      training/match days lost and suspected cause) with 100% compliance. Time periods
      during the tournament were divided as follows: located and playing in the home
      country before travelling (baseline), located and playing abroad in countries >5
      h time zone difference (travel) and located back in the home country following
      international travel (return). MAIN OUTCOME MEASUREMENT: Incidence of illness
      (illness per 1000 player-days) during baseline, travel and return. RESULTS: The
      overall incidence of illness in the cohort was 20.7 (95% CI 18.5 to 23.1). For
      all teams, the incidence of illness according to location and travelling was
      significantly higher in the time period following international travel (32.6; 95%
      CI 19.6 to 53.5) compared with the baseline (15.4; 95% CI 8.7 to 27.0) or after
      returning to their home country (10.6; 95% CI 6.1 to 18.2). CONCLUSIONS: There is
      a higher incidence of illness in athletes following international travel to a
      foreign country that is >5 h time difference and this returns to baseline on
      return to the home country.

PMID- 22875911
TI  - Minimal residual disease monitoring by quantitative RT-PCR in core binding factor
      AML allows risk stratification and predicts relapse: results of the United
      Kingdom MRC AML-15 trial.
AB  - The clinical value of serial minimal residual disease (MRD) monitoring in core
      binding factor (CBF) acute myeloid leukemia (AML) by quantitative RT-PCR was
      prospectively assessed in 278 patients [163 with t(8;21) and 115 with inv(16)]
      entered in the United Kingdom MRC AML 15 trial. CBF transcripts were normalized
      to 10(5) ABL copies. At remission, after course 1 induction chemotherapy, a > 3
      log reduction in RUNX1-RUNX1T1 transcripts in BM in t(8;21) patients and a > 10
      CBFB-MYH11 copy number in peripheral blood (PB) in inv(16) patients were the most
      useful prognostic variables for relapse risk on multivariate analysis. MRD levels
      after consolidation (course 3) were also informative. During follow-up, cut-off
      MRD thresholds in BM and PB associated with a 100% relapse rate were identified:
      for t(8;21) patients BM > 500 copies, PB > 100 copies; for inv(16) patients, BM >
      50 copies and PB > 10 copies. Rising MRD levels on serial monitoring accurately
      predicted hematologic relapse. During follow-up, PB sampling was equally
      informative as BM for MRD detection. We conclude that MRD monitoring by
      quantitative RT-PCR at specific time points in CBF AML allows identification of
      patients at high risk of relapse and could now be incorporated in clinical trials
      to evaluate the role of risk directed/preemptive therapy.

PMID- 22875912
TI  - Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells that depend
      on host factors in the tissue microenvironment for survival and proliferation. In
      vitro, CLL cells rapidly undergo apoptosis unless microenvironmental factors are
      provided that support their survival. Signaling pathways activated in the
      microenvironment in vivo include the B-cell receptor (BCR) and NF-kappaB
      pathways. Thus, CLL is a disease "addicted to the host" and is dependent on
      pathways that promote normal B-cell development, expansion, and survival; this is
      particularly true in the case of the BCR signaling cascade. Small-molecule
      inhibitors of kinases that are essential for BCR signal transduction abrogate the
      stimulating effects of the microenvironment on CLL cells. The orally administered
      tyrosine kinase inhibitors fostamatinib and ibrutinib and the
      phosphatidylinositol 3-kinase inhibitor GS-1101 have induced impressive responses
      in relapsed and refractory CLL patients, mostly with moderate side effects.
      Reductions in lymphadenopathy and splenomegaly are seen within weeks and are
      frequently accompanied by a transient rise in absolute lymphocyte count that is
      asymptomatic and probably the result of changes in CLL cell trafficking. This
      review discusses the biologic basis for kinase inhibitors as targeted therapy of
      CLL and summarizes the exciting early clinical experience with these agents.

PMID- 22875914
TI  - Unraveling acetylcholine impact on human cortical plasticity.

PMID- 22875913
TI  - T-cell independent, B-cell receptor-mediated induction of telomerase activity
      differs among IGHV mutation-based subgroups of chronic lymphocytic leukemia
      patients.
AB  - Although B-cell chronic lymphocytic leukemia (B-CLL) clones with unmutated IGHV
      genes (U-CLL) exhibit greater telomerase activity than those with mutated IGHV
      genes (M-CLL), the extent to which B-cell receptor (BCR) triggering contributes
      to telomerase up-regulation is not known. Therefore, we studied the effect of BCR
      stimulation on modulating telomerase activity. The multivalent BCR ligand,
      dextran conjugated anti-MU mAb HB57 (HB57-dex), increased telomerase activity and
      promoted cell survival and proliferation preferentially in U-CLL cases, whereas
      the PI3K/Akt inhibitor LY294002 blocked HB57-dex induced telomerase activation.
      Although both U-CLL and M-CLL clones exhibited similar membrane proximal
      signaling responses to HB57-dex, telomerase activity and cell proliferation, when
      inducible in M-CLL, differed. B-CLL cells stimulated using bivalent F(ab')(2) 
      goat anti-MU antibody (goat anti-MU) exhibited higher membrane proximal response
      in U-CLL than M-CLL cells, whereas telomerase activity, cell survival, and
      proliferation were induced to lower levels than those induced by HB57-dex. In
      normal B lymphocytes, HB57-dex induced less protein phosphorylation but more cell
      proliferation and survival than goat anti-MU. Although both anti-BCR stimuli
      induced comparable telomerase activity, normal CD5(+) B cells preferentially
      exhibited higher hTERT positivity than their CD5(-) counterparts. These findings
      provide an understanding of how BCR-mediated signals impact telomerase modulation
      in IGHV mutation-based subgroups of B-CLL and normal B cells.

PMID- 22875915
TI  - Supraspinal peroxynitrite modulates pain signaling by suppressing the endogenous
      opioid pathway.
AB  - Peroxynitrite (PN, ONOO(-)) is a potent oxidant and nitrating agent that
      contributes to pain through peripheral and spinal mechanisms, but its supraspinal
      role is unknown. We present evidence here that PN in the rostral ventromedial
      medulla (RVM) is essential for descending nociceptive modulation in rats during
      inflammatory and neuropathic pain through PN-mediated suppression of opioid
      signaling. Carrageenan-induced thermal hyperalgesia was associated with increased
      3-nitrotyrosine (NT), a PN biomarker, in the RVM. Furthermore, intra-RVM
      microinjections of the PN decomposition catalyst Fe(III)-5,10,15,20-tetrakis(N
      methyl-pyridinium-4-yl)porphyrin (FeTMPyP(5+)) dose-dependently reversed this
      thermal hyperalgesia. These effects of FeTMPyP(5+) were abrogated by intra-RVM
      naloxone, implicating potential interplay between PN and opioids. In support, we
      identified NT colocalization with the endogenous opioid enkephalin (ENK) in the
      RVM during thermal hyperalgesia, suggesting potential in situ interactions. To
      address the functional significance of such interactions, we exposed methionine
      enkephalin (MENK) to PN and identified the major metabolite, 3-nitrotyrosine
      methionine-sulfoxide (NSO)-MENK, using liquid chromatography-mass spectrometry.
      Next, we isolated, purified, and tested NSO-MENK for opioid receptor binding
      affinity and analgesic effects. Compared to MENK, this NSO-MENK metabolite lacked
      appreciable binding affinity for delta, MU, and kappa opioid receptors.
      Intrathecal injection of NSO-MENK in rats did not evoke antinociception,
      suggesting that PN-mediated chemical modifications of ENK suppress opioid
      signaling. When extended to chronic pain, intra-RVM FeTMPyP(5+) produced naloxone
      sensitive reversal of mechanical allodynia in rats following chronic constriction
      injury of the sciatic nerve. Collectively, our data reveal the central role of PN
      in RVM descending facilitation during inflammatory and neuropathic pain
      potentially through anti-opioid activity.

PMID- 22875916
TI  - Reactive astrocytes overexpress TSPO and are detected by TSPO positron emission
      tomography imaging.
AB  - Astrocytes and microglia become reactive under most brain pathological
      conditions, making this neuroinflammation process a surrogate marker of neuronal
      dysfunction. Neuroinflammation is associated with increased levels of
      translocator protein 18 kDa (TSPO) and binding sites for TSPO ligands. Positron
      emission tomography (PET) imaging of TSPO is thus commonly used to monitor
      neuroinflammation in preclinical and clinical studies. It is widely considered
      that TSPO PET signal reveals reactive microglia, although a few studies suggested
      a potential contribution of reactive astrocytes. Because astrocytes and microglia
      play very different roles, it is crucial to determine whether reactive astrocytes
      can also overexpress TSPO and yield to a detectable TSPO PET signal in vivo. We
      used a model of selective astrocyte activation through lentiviral gene transfer
      of the cytokine ciliary neurotrophic factor (CNTF) into the rat striatum, in the
      absence of neurodegeneration. CNTF induced an extensive activation of astrocytes,
      which overexpressed GFAP and become hypertrophic, whereas microglia displayed
      minimal increase in reactive markers. Two TSPO radioligands, [(18)F]DPA-714 [N,N
      diethyl-2-(2-(4-(2-[(18)F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5
      a]pyrimidin-3-yl)acetamide] and [(11)C]SSR180575 (7-chloro-N,N-dimethyl-5
      [(11)C]methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide),
      showed a significant binding in the lenti-CNTF-injected striatum that was
      saturated and displaced by PK11195 [N-methyl-N-(1-methylpropyl)-1-(2
      chlorophenyl)-isoquinoline-3-carboxamide]. The volume of radioligand binding
      matched the GFAP immunopositive volume. TSPO mRNA levels were significantly
      increased, and TSPO protein was overexpressed by CNTF-activated astrocytes. We
      show that reactive astrocytes overexpress TSPO, yielding to a significant and
      selective binding of TSPO radioligands. Therefore, caution must be used when
      interpreting TSPO PET imaging in animals or patients because reactive astrocytes
      can contribute to the signal in addition to reactive microglia.

PMID- 22875917
TI  - Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn
      injury.
AB  - Marked hypersensitivity to heat and mechanical (pressure) stimuli develop after a
      burn injury, but the neural mechanisms underlying these effects are poorly
      understood. In this study, we establish a new mouse model of focal second-degree
      burn injury to investigate the molecular and cellular basis for burn injury
      induced pain. This model features robust injury-induced behavioral effects and
      tissue-specific altered cytokine profile, but absence of glial activation in
      spinal dorsal horn. Three voltage-gated sodium channels, Na(v)1.7, Na(v)1.8, and
      Na(v)1.9, are preferentially expressed in peripheral somatosensory neurons of the
      dorsal root ganglia (DRGs) and have been implicated in injury-induced neuronal
      hyperexcitability. Using knock-out mice, we provide evidence that Na(v)1.7
      selectively contributes to burn-induced hypersensitivity to heat, but not
      mechanical, stimuli. After burn model injury, wild-type mice display increased
      sensitivity to heat stimuli, and a normally non-noxious warm stimulus induces
      activity-dependent Fos expression in spinal dorsal horn neurons. Strikingly, both
      effects are absent in Na(v)1.7 conditional knock-out (cKO) mice. Furthermore,
      burn injury increases density and shifts activation of tetrodotoxin-sensitive
      currents in a hyperpolarized direction, both pro-excitatory properties, in DRG
      neurons from wild-type but not Na(v)1.7 cKO mice. We propose that, in sensory
      neurons damaged by burn injury to the hindpaw, Na(v)1.7 currents contribute to
      the hyperexcitability of sensory neurons, their communication with postsynaptic
      spinal pain pathways, and behavioral thresholds to heat stimuli. Our results
      offer insights into the molecular and cellular mechanisms of modality-specific
      pain signaling, and suggest Na(v)1.7-blocking drugs may be effective in burn
      patients.

PMID- 22875918
TI  - Chronic-pain-associated astrocytic reaction in the spinal cord dorsal horn of
      human immunodeficiency virus-infected patients.
AB  - Studies with animal models have suggested that reaction of glia, including
      microglia and astrocytes, critically contributes to the development and
      maintenance of chronic pain. However, the involvement of glial reaction in human
      chronic pain is unclear. We performed analyses to compare the glial reaction
      profiles in the spinal dorsal horn (SDH) from three cohorts of sex- and age
      matched human postmortem tissues: (1) HIV-negative patients, (2) HIV-positive
      patients without chronic pain, and (3) HIV patients with chronic pain. Our
      results indicate that the expression levels of CD11b and Iba1, commonly used for
      labeling microglial cells, did not differ in the three patient groups. However,
      GFAP and S100beta, often used for labeling astrocytes, were specifically
      upregulated in the SDH of the "pain-positive" HIV patients but not in the "pain
      negative" HIV patients. In addition, proinflammatory cytokines, TNFalpha and IL
      1beta, were specifically increased in the SDH of pain-positive HIV patients.
      Furthermore, proteins in the MAPK signaling pathway, including pERK, pCREB and c
      Fos, were also upregulated in the SDH of pain-positive HIV patients. Our findings
      suggest that reaction of astrocytes in the SDH may play a role during the
      maintenance phase of HIV-associated chronic pain.

PMID- 22875919
TI  - Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the
      astrocytic compartment.
AB  - Delineation of key molecules that act epigenetically to transduce diverse
      stressors into established patterns of disease would facilitate the advent of
      preventive and disease-modifying therapeutics for a host of neurological
      disorders. Herein, we demonstrate that selective overexpression of the stress
      protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice
      results in subcortical oxidative stress and mitochondrial damage/autophagy;
      diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with
      attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine
      hydroxylase and alpha-synuclein expression with downregulation of the targeting
      miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia;
      reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and
      altered hippocampal cytoarchitectonics; impaired neurovascular coupling;
      attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1
      neurophenotype bears resemblances to human schizophrenia and other
      neurodevelopmental conditions and implicates glial HO-1 as a prime transducer of
      inimical (endogenous and environmental) influences on the development of
      monoaminergic circuitry. Containment of the glial HO-1 response to noxious
      stimuli at strategic points of the life cycle may afford novel opportunities for
      the effective management of human neurodevelopmental and neurodegenerative
      conditions.

PMID- 22875920
TI  - Organization of cerebral projections to identified cerebellar zones in the
      posterior cerebellum of the rat.
AB  - The cerebrocerebellar connection makes use of two of the largest fiber tracts in
      the mammalian brain, i.e., the cerebral and medial cerebellar peduncles.
      Neuroanatomical approaches aimed to elucidate the organization of this important
      connection have been hindered by its multisynaptic nature, the complex
      organization of its components, and the dependency of conventional tracers on
      precisely placed injections. To overcome these problems, we used rabies virus
      (RV) as a retrograde transneuronal tracer. RV was injected simultaneously with
      cholera toxin beta subunit (CTb) into selected areas of the cerebellar cortex of
      18 male Wistar rats. A survival time of 48-50 h resulted in first- and second
      order labeling of RV in combination with first-order labeling of CTb. The
      distribution of CTb-labeled neurons in the inferior olive established the zonal
      identity of the injection site. In this way, it was possible to examine the
      cortical distribution of neurons from which disynaptic cerebrocerebellar
      projections to specific cerebellar loci originate. The results show that this
      distribution covaries with the identity of the injected cerebellar lobule. More
      subtle changes were present when different zones of the same lobule were
      injected. The C1 zone of lobule VIII receives a more prominent projection from
      the somatosensory cortex compared with the C2/D zones. The laterally positioned D
      zones receive information from more rostral regions of the cerebral cortex. The
      vermis of lobule VII receives a prominent input from the retrosplenial and
      orbitofrontal cortices. Different injection sites also result in differences in
      laterality of the connections.

PMID- 22875921
TI  - How preparation changes the need for top-down control of the basal ganglia when
      inhibiting premature actions.
AB  - Goal-oriented signals from the prefrontal cortex gate the selection of
      appropriate actions in the basal ganglia. Key nodes within this fronto-basal
      ganglia action regulation network are increasingly engaged when one anticipates
      the need to inhibit and override planned actions. Here, we ask how the advance
      preparation of action plans modulates the need for fronto-subcortical control
      when a planned action needs to be withdrawn. Functional magnetic resonance
      imaging data were collected while human participants performed a stop task with
      cues indicating the likelihood of a stop signal being sounded. Mathematical
      modeling of go trial responses suggested that participants attained a more
      cautious response strategy when the probability of a stop signal increased.
      Effective connectivity analysis indicated that, even in the absence of stop
      signals, the proactive engagement of the full control network is tailored to the
      likelihood of stop trial occurrence. Importantly, during actual stop trials, the
      strength of fronto-subcortical projections was stronger when stopping had to be
      engaged reactively compared with when it was proactively prepared in advance.
      These findings suggest that fronto-basal ganglia control is strongest in an
      unpredictable environment, where the prefrontal cortex plays an important role in
      the optimization of reactive control. Importantly, these results further indicate
      that the advance preparation of action plans reduces the need for reactive fronto
      basal ganglia communication to gate voluntary actions.

PMID- 22875922
TI  - An essential role for histone deacetylase 4 in synaptic plasticity and memory
      formation.
AB  - Histone deacetylases (HDACs), a family of enzymes involved in epigenetic
      regulation, have been implicated in the control of synaptic plasticity, as well
      as learning and memory. Previous work has demonstrated administration of
      pharmacological HDAC inhibitors, primarily those targeted to class I HDACs,
      enhance learning and memory as well as long-term potentiation. However, a
      detailed understanding of the role of class II HDACs in these processes remains
      elusive. Here, we show that selective loss of Hdac4 in brain results in
      impairments in hippocampal-dependent learning and memory and long-term synaptic
      plasticity. In contrast, loss of Hdac5 does not impact learning and memory
      demonstrating unique roles in brain for individual class II HDACs. These findings
      suggest that HDAC4 is a crucial positive regulator of learning and memory, both
      behaviorally and at the cellular level, and that inhibition of Hdac4 activity may
      have unexpected detrimental effects to these processes.

PMID- 22875923
TI  - Normal midbrain dopaminergic neuron development and function in miR-133b mutant
      mice.
AB  - Midbrain dopaminergic (mDA) neurons control movement and emotion, and their
      degeneration leads to motor and cognitive defects in Parkinson's disease (PD).
      miR-133b is a conserved microRNA that is thought to regulate mDA neuron
      differentiation by targeting Pitx3, a transcription factor required for
      appropriate development of mDA substantia nigra neurons. Moreover, miR-133b has
      been found to be depleted in the midbrain of PD patients. However, the function
      of miR-133b in the intact midbrain has not been determined. Here we show that miR
      133b null mice have normal numbers of mDA neurons during development and aging.
      Dopamine levels are unchanged in the striatum, while expression of dopaminergic
      genes, including Pitx3, is also unaffected. Finally, motor coordination and both
      spontaneous and psychostimulant-induced locomotion are unaltered in miR-133b null
      mice, suggesting that miR-133b does not play a significant role in mDA neuron
      development and maintenance in vivo.

PMID- 22875924
TI  - Afferents from vocal motor and respiratory effectors are recruited during vocal
      production in juvenile songbirds.
AB  - Learned behaviors require coordination of diverse sensory inputs with
      motivational and motor systems. Although mechanisms underlying vocal learning in
      songbirds have focused primarily on auditory inputs, it is likely that sensory
      inputs from vocal effectors also provide essential feedback. We investigated the
      role of somatosensory and respiratory inputs from vocal effectors of juvenile
      zebra finches (Taeniopygia guttata) during the stage of sensorimotor integration
      when they are learning to imitate a previously memorized tutor song. We report
      that song production induced expression of the immediate early gene product Fos
      in trigeminal regions that receive hypoglossal afferents from the tongue and
      syrinx (the main vocal organ). Furthermore, unilateral lesion of hypoglossal
      afferents greatly diminished singing-induced Fos expression on the side
      ipsilateral to the lesion, but not on the intact control side. In addition,
      unilateral lesion of the vagus reduced Fos expression in the ipsilateral nucleus
      of the solitary tract in singing birds. Lesion of the hypoglossal nerve to the
      syrinx greatly disrupted vocal behavior, whereas lesion of the hypoglossal nerve
      to the tongue exerted no obvious disruption and lesions of the vagus caused some
      alterations to song behavior. These results provide the first functional evidence
      that somatosensory and respiratory feedback from peripheral effectors is
      activated during vocal production and conveyed to brainstem regions. Such
      feedback is likely to play an important role in vocal learning during
      sensorimotor integration in juvenile birds and in maintaining stereotyped vocal
      behavior in adults.

PMID- 22875925
TI  - Persistent spatial information in the frontal eye field during object-based short
      term memory.
AB  - Spatial attention is known to gate entry into visual short-term memory, and some
      evidence suggests that spatial signals may also play a role in binding features
      or protecting object representations during memory maintenance. To examine the
      persistence of spatial signals during object short-term memory, the activity of
      neurons in the frontal eye field (FEF) of macaque monkeys was recorded during an
      object-based delayed match-to-sample task. In this task, monkeys were trained to
      remember an object image over a brief delay, regardless of the locations of the
      sample or target presentation. FEF neurons exhibited visual, delay, and target
      period activity, including selectivity for sample location and target location.
      Delay period activity represented the sample location throughout the delay,
      despite the irrelevance of spatial information for successful task completion.
      Furthermore, neurons continued to encode sample position in a variant of the task
      in which the matching stimulus never appeared in their response field, confirming
      that FEF maintains sample location independent of subsequent behavioral
      relevance. FEF neurons also exhibited target-position-dependent anticipatory
      activity immediately before target onset, suggesting that monkeys predicted
      target position within blocks. These results show that FEF neurons maintain
      spatial information during short-term memory, even when that information is
      irrelevant for task performance.

PMID- 22875926
TI  - Hippocampal-prefrontal cortical circuit mediates inhibitory response control in
      the rat.
AB  - We investigated the interdependent function of the ventral hippocampus (vHC) and
      ventral prefrontal cortex (vPFC) in visuospatial attention and inhibitory control
      using a disconnection lesion approach. Rats were trained, and several aspects of
      their cognitive performance tested on the 5-choice reaction time task. The
      animals were prepared with unilateral lesions of both the vPFC and vHC, either in
      the same hemisphere ("ipsilateral") or in opposite hemispheres ("disconnection").
      The disconnection lesion led to both impulsive and compulsive behavior. This
      deficit is reminiscent of the effects of either bilateral vPFC or bilateral vHC
      lesions on the same task and is thought to reflect the bihemispheric disruption
      of the hippocampal-prefrontal circuit. With ipsilateral lesions, behavioral
      deficits were transient or absent altogether, suggesting that the intact
      hemisphere was able to exert near normal levels of behavioral control. These
      behavioral effects were observed in the absence of any changes to visual
      attention, speed of response, or general motivation. This study provides evidence
      that optimal inhibitory control of behavior draws upon the functional interaction
      between the vHC and vPFC.

PMID- 22875927
TI  - A gradient in endogenous rhythmicity and oscillatory drive matches recruitment
      order in an axial motor pool.
AB  - The rhythmic firing behavior of spinal motoneurons is a function of their
      electrical properties and synaptic inputs. However, the relative contribution of
      endogenous versus network-based rhythmogenic mechanisms to locomotion is unclear.
      To address this issue, we have recorded from identified motoneurons and compared
      their current-evoked firing patterns to network-driven ones in the larval
      zebrafish (Danio rerio). Zebrafish axial motoneurons are recruited
      topographically from the bottom of the spinal cord up. Here, we have explored
      differences in the morphology of axial motoneurons, their electrical properties,
      and their synaptic drive, to reveal how they match the topographic pattern of
      recruitment. More ventrally located "secondary" motoneurons generate bursts of
      action potentials in response to constant current steps, demonstrating a strong
      inherent rhythmogenesis. The membrane potential oscillations underlying bursting
      behavior occur in the normal frequency range of swimming. In contrast, more
      dorsal secondaries chatter in response to current, while the most dorsally
      distributed "primary" motoneurons all fire tonically. We find that systematic
      variations in excitability and endogenous rhythmicity are inversely related to
      the level of oscillatory synaptic drive within the entire axial motor pool.
      Specifically, bursting cells exhibit the least amount of drive, while tonic cells
      exhibit the most. Our data suggest that increases in swimming frequency are
      accomplished by the recruitment of axial motoneurons that progressively rely on
      instructive synaptic drive to shape their oscillatory activity appropriately.
      Thus, within the zebrafish spinal cord, there are differences in the relative
      contribution of endogenous versus network-based rhythms to locomotion and these
      vary predictably according to order of recruitment.

PMID- 22875928
TI  - Fezf2 regulates multilineage neuronal differentiation through activating basic
      helix-loop-helix and homeodomain genes in the zebrafish ventral forebrain.
AB  - Transcription factors of the achaete-scute and atonal bHLH proneural gene family
      play important roles in neuronal differentiation. They are also involved in
      neuronal subtype specification through collaboration with homeodomain (HD)
      transcription factors. However, concerted regulation of these genes and in turn
      progenitor fate toward distinct lineages within the developing vertebrate brain
      is not well understood. Fezf2 is an evolutionarily conserved zinc finger protein
      important for monoaminergic neuronal development in zebrafish. Here, we show that
      Fezf2 is also critical for GABAergic neuronal fate and investigate how a single
      transcription factor regulates the identity of multiple neuronal lineages in the
      developing ventral forebrain. First, our genetic analyses reveal the requirement
      of the achaete-scute-like genes ascl1a and 1b in serotonergic and GABAergic
      neuron development, but they are dispensable for the specification of
      dopaminergic neurons, which is dependent on the atonal-like gene neurog1. Second,
      the expression of fezf2, ascl1a/1b, and neurog1 demarcates distinct progenitor
      subpopulations, where fezf2 is required for activating but not maintaining the
      expression of bHLH genes. Third, Fezf2 is required to activate HD genes otpb and
      dlx2, which are involved in dopaminergic and GABAergic neuronal development,
      respectively. Finally, we uncover that Fezf2 is sufficient to increase
      dopaminergic neuronal numbers but not serotonergic or GABAergic lineages.
      Together, these findings reveal new mechanisms by which multilineage
      differentiation is coordinately regulated by a single transcription factor in the
      vertebrate ventral forebrain.

PMID- 22875929
TI  - Early development of electrical excitability in the mouse enteric nervous system.
AB  - Neural activity is integral to the development of the enteric nervous system
      (ENS). A subpopulation of neural crest-derived cells expresses pan-neuronal
      markers at early stages of ENS development (at E10.5 in the mouse). However, the
      electrical activity of these cells has not been previously characterized, and it
      is not known whether all cells expressing neuronal markers are capable of firing
      action potentials (APs). In this study, we examined the activity of "neuron"-like
      cells (expressing pan-neuronal markers or with neuronal morphology) in the gut of
      E11.5 and E12.5 mice using whole-cell patch-clamp electrophysiology and compared
      them to the activity of neonatal and adult enteric neurons. Around 30-40% of
      neuron-like cells at E11.5 and E12.5 fired APs, some of which were very similar
      to those of adult enteric neurons. All APs were sensitive to tetrodotoxin (TTX),
      indicating that they were driven by voltage-gated Na+ currents. Expression of
      mRNA encoding several voltage-gated Na+ channels by the E11.5 gut was detected
      using RT-PCR. The density of voltage-gated Na+ currents increased from E11.5 to
      neonates. Immature active responses, mediated in part by TTX- and lidocaine
      insensitive channels, were observed in most cells at E11.5 and E12.5, but not in
      P0/P1 or adult neurons. However, some cells expressing neuronal markers at E11.5
      or E12.5 did not exhibit an active response to depolarization. Spontaneous
      depolarizations resembling excitatory postsynaptic potentials were observed at
      E12.5. The ENS is one of the earliest parts of the developing nervous system to
      exhibit mature forms of electrical activity.

PMID- 22875930
TI  - Effect of locomotor training in completely spinalized cats previously submitted
      to a spinal hemisection.
AB  - After a spinal hemisection in cats, locomotor plasticity occurring at the spinal
      level can be revealed by performing, several weeks later, a complete
      spinalization below the first hemisection. Using this paradigm, we recently
      demonstrated that the hemisection induces durable changes in the symmetry of
      locomotor kinematics that persist after spinalization. Can this asymmetry be
      changed again in the spinal state by interventions such as treadmill locomotor
      training started within a few days after the spinalization? We performed, in 9
      adult cats, a spinal hemisection at thoracic level 10 and then a complete
      spinalization at T13, 3 weeks later. Cats were not treadmill trained during the
      hemispinal period. After spinalization, 5 of 9 cats were not trained and served
      as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week
      for 3 weeks. Using detailed kinematic analyses, we showed that, without training,
      the asymmetrical state of locomotion induced by the hemisection was retained
      durably after the subsequent spinalization. By contrast, training cats after
      spinalization induced a reversal of the left/right asymmetries, suggesting that
      new plastic changes occurred within the spinal cord through locomotor training.
      Moreover, training was shown to improve the kinematic parameters and the
      performance of the hindlimb on the previously hemisected side. These results
      indicate that spinal locomotor circuits, previously modified by past experience
      such as required for adaptation to the hemisection, can remarkably respond to
      subsequent locomotor training and improve bilateral locomotor kinematics, clearly
      showing the benefits of locomotor training in the spinal state.

PMID- 22875932
TI  - Voltage-sensitive dye imaging reveals dynamic spatiotemporal properties of
      cortical activity after spontaneous muscle twitches in the newborn rat.
AB  - Spontaneous activity in the developing brain contributes to its maturation, but
      how this activity is coordinated between distinct cortical regions and whether it
      might reflect developing sensory circuits is not well understood. Here, we
      address this question by imaging the spread and synchronization of cortical
      activity using voltage-sensitive dyes (VSDs) in the developing rat in vivo. In
      postnatal day 4-6 rats (n = 10), we collected spontaneous changes in VSD signal
      that reflect underlying membrane potential changes over a large craniotomy (50
      mm2) that encompassed both the sensory and motor cortices of both hemispheres.
      Bursts of depolarization that occurred approximately once every 12 s were
      preceded by spontaneous twitches of the hindlimbs and/or tail. The close
      association with peripheral movements suggests that these bursts may represent a
      slow component of spindle bursts, a prominent form of activity in the developing
      somatosensory cortex. Twitch-associated cortical activity was synchronized
      between subregions of somatosensory cortex, which reflected the synchronized
      twitching of the limbs and tail. This activity also spread asymmetrically, toward
      the midline of the brain. We found that the spatial and temporal structure of
      such spontaneous cortical bursts closely matched that of sensory-evoked activity
      elicited via direct stimulation of the periphery. These data suggest that
      spontaneous cortical activity provides a recurring template of functional
      cortical circuits within the developing cortex and could contribute to the
      maturation of integrative connections between sensory and motor cortices.

PMID- 22875931
TI  - Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor
      protein in neurodegeneration.
AB  - The importance of ubiquitin E3 ligases in neurodegeneration is being increasingly
      recognized. The crucial role of NEDD4-1 in neural development is well
      appreciated; however, its role in neurodegeneration remains unexplored. Herein,
      we report increased NEDD4-1 expression in the degenerated tissues of several
      major neurodegenerative diseases. Moreover, its expression is upregulated in
      cultured neurons in response to various neurotoxins, including zinc and hydrogen
      superoxide, via transcriptional activation likely mediated by the reactive oxygen
      species (ROS)-responsive FOXM1B. Reduced protein levels of the insulin-like
      growth factor receptor (IGF-1Rbeta) were observed as a consequence of upregulated
      NEDD4-1 via the ubiquitin-proteasome system. Overexpression of a familial mutant
      form of superoxide dismutase 1 (SOD1) (G93A) in neuroblastoma cells resulted in a
      similar reduction of IGF-1Rbeta protein. This inverse correlation between NEDD4-1
      and IGF-1Rbeta was also observed in the cortex and spinal cords of mutant (G93A)
      SOD1 transgenic mice at a presymptomatic age, which was similarly induced by in
      vivo-administered zinc in wild-type C57BL/6 mice. Furthermore, histochemistry
      reveals markedly increased NEDD4-1 immunoreactivity in the
      degenerating/degenerated motor neurons in the lumbar anterior horn of the spinal
      cord, suggesting a direct causative role for NEDD4-1 in neurodegeneration.
      Indeed, downregulation of NEDD4-1 by shRNA or overexpression of a catalytically
      inactive form rescued neurons from zinc-induced cell death. Similarly, neurons
      with a NEDD4-1 haplotype are more resistant to apoptosis, largely due to
      expression of higher levels of IGF-1Rbeta.Together, our work identifies a novel
      molecular mechanism for ROS-upregulated NEDD4-1 and the subsequently reduced IGF
      1Rbeta signaling in neurodegeneration.

PMID- 22875933
TI  - Increase in sodium conductance decreases firing rate and gain in model neurons.
AB  - We studied the effects of increased sodium conductance on firing rate and gain in
      two populations of conductance-based, single-compartment model neurons. The first
      population consisted of 1000 model neurons with differing values of seven voltage
      dependent conductances. In many of these models, increasing the sodium
      conductance threefold unexpectedly reduced the firing rate and divisively scaled
      the gain at high input current. In the second population, consisting of 1000
      simplified model neurons, we found that enhanced sodium conductance changed the
      frequency-current (FI) curve in two computationally distinct ways, depending on
      the firing rate. In these models, increased sodium conductance produced a
      subtractive shift in the FI curve at low firing rates because the additional
      sodium conductance allowed the neuron to respond more strongly to equivalent
      input current. In contrast, at high input current, the increase in sodium
      conductance resulted in a divisive change in the gain because the increased
      conductance produced a proportionally larger activation of the delayed rectifier
      potassium conductance. The control and sodium-enhanced FI curves intersect at a
      point that delimits two regions in which the same biophysical manipulation
      produces two fundamentally different changes to the model neuron's computational
      properties. This suggests a potentially difficult problem for homeostatic
      regulation of intrinsic excitability.

PMID- 22875934
TI  - What and where information in the caudate tail guides saccades to visual objects.
AB  - We understand the world by making saccadic eye movements to various objects.
      However, it is unclear how a saccade can be aimed at a particular object, because
      two kinds of visual information, what the object is and where it is, are
      processed separately in the dorsal and ventral visual cortical pathways. Here, we
      provide evidence suggesting that a basal ganglia circuit through the tail of the
      monkey caudate nucleus (CDt) guides such object-directed saccades. First, many
      CDt neurons responded to visual objects depending on where and what the objects
      were. Second, electrical stimulation in the CDt induced saccades whose directions
      matched the preferred directions of neurons at the stimulation site. Third, many
      CDt neurons increased their activity before saccades directed to the preferred
      objects and directions of the neurons in a free-viewing condition. Our results
      suggest that CDt neurons receive both "what" and "where" information and guide
      saccades to visual objects.

PMID- 22875935
TI  - Neuronal activity during a cued strategy task: comparison of dorsolateral,
      orbital, and polar prefrontal cortex.
AB  - We compared neuronal activity in the dorsolateral (PFdl), orbital (PFo), and
      polar (PFp) prefrontal cortex as monkeys performed three tasks. In two tasks, a
      cue instructed one of two strategies: stay with the previous response or shift to
      the alternative. Visual stimuli served as cues in one of these tasks; in the
      other, fluid rewards did so. In the third task, visuospatial cues instructed each
      response. A delay period followed each cue. As reported previously, PFdl encoded
      strategies (stay or shift) and responses (left or right) during the cue and delay
      periods, while PFo encoded strategies and PFp encoded neither strategies nor
      responses; during the feedback period, all three areas encoded responses, but not
      strategies. Four novel findings emerged from the present analysis. (1) The
      strategy encoded by PFdl and PFo cells during the cue and delay periods was
      modality specific. (2) The response encoded by PFdl cells was task and modality
      specific during the cue period, but during the delay and feedback periods it
      became task and modality general. (3) Although some PFdl and PFo cells responded
      to or anticipated rewards, we could rule out reward effects for most strategy-
      and response-related activity. (4) Immediately before feedback, only PFp signaled
      responses that were correct according to the cued strategy; after feedback, only
      PFo signaled the response that had been made, whether correct or incorrect. These
      signals support a role in generating responses by PFdl, assigning outcomes to
      choices by PFo, and assigning outcomes to cognitive processes by PFp.

PMID- 22875936
TI  - Role of dopamine tone in the pursuit of brain stimulation reward.
AB  - Dopaminergic neurons contribute to intracranial self-stimulation (ICSS) and other
      reward-seeking behaviors, but it is not yet known where dopaminergic neurons
      intervene in the neural circuitry underlying reward pursuit or which
      psychological processes are involved. In rats working for electrical stimulation
      of the medial forebrain bundle, we assessed the effect of GBR-12909 (1-[2-[bis(4
      fluorophenyl)-methoxy]ethyl]-4-[3- phenylpropyl]piperazine), a specific blocker
      of the dopamine transporter. Operant performance was measured as a function of
      the strength and cost of electrical stimulation. GBR-12909 increased the
      opportunity cost most subjects were willing to pay for a reward of a given
      intensity. However, this effect was smaller than that produced by a regimen of
      cocaine administration that drove similar increases in nucleus accumbens (NAc)
      dopamine levels in unstimulated rats. Delivery of rewarding stimulation to drug
      treated rats caused an additional increase in dopamine concentration in the NAc
      shell in cocaine-treated, but not GBR-12909-treated, rats. These behavioral and
      neurochemical differences may reflect blockade of the norepinephrine transporter
      by cocaine but not by GBR-12909. Whereas the effect of psychomotor stimulants on
      ICSS has long been attributed to dopaminergic action at early stages of the
      reward pathway, the results reported here imply that increased dopamine tone
      boosts reward pursuit by acting at or beyond the output of the circuitry that
      temporally and spatially summates the output of the directly stimulated neurons
      underlying ICSS. The observed enhancement of reward seeking could be attributable
      to a decrease in the value of competing behaviors, a decrease in subjective
      effort costs, or an increase in reward-system gain.

PMID- 22875937
TI  - Stress modulates the engagement of multiple memory systems in classification
      learning.
AB  - Learning and memory are supported by anatomically and functionally distinct
      systems. Recent research suggests that stress may alter the contributions of
      multiple memory systems to learning, yet the underlying mechanism in the human
      brain remains completely unknown. Using event-related functional magnetic
      resonance imaging, we asked in the present experiment whether stress may modulate
      the engagement of hippocampus-based "declarative" and striatum-based "procedural"
      memory systems during classification learning in humans and what brain mechanisms
      are involved in this effect. We found that stress reduced declarative knowledge
      about the learning task and changed the used learning strategy from a single-cue
      based declarative strategy to a multicue-based procedural strategy, whereas
      learning performance per se remained unaffected by stress. Neuroimaging revealed
      that hippocampal activity correlated positively with task performance in the
      control condition, whereas striatal activity correlated with performance in the
      stress condition. After stress, hippocampal activity was reduced and even
      negatively correlated with learning performance. These findings show for the
      first time that stress alters the engagement of multiple memory systems in the
      human brain. Stress impaired the hippocampus-dependent system and allowed the
      striatum to control behavior. The shift toward "procedural" learning after stress
      appears to rescue task performance, whereas attempts to engage the "declarative"
      system disrupt performance.

PMID- 22875938
TI  - Activation of Aurora-A is essential for neuronal migration via modulation of
      microtubule organization.
AB  - Neuronal migration is a critical feature to ensure proper location and wiring of
      neurons during cortical development. Postmitotic neurons migrate from the
      ventricular zone into the cortical plate to establish neuronal lamina in an
      "inside-out" gradient of maturation. Here, we report that the mitotic kinase
      Aurora-A is critical for the regulation of microtubule organization during
      neuronal migration via an Aurora-A-NDEL1 pathway in the mouse. Suppression of
      Aurora-A activity by inhibitors or siRNA resulted in severe impairment of
      neuronal migration of granular neurons. In addition, in utero injection of the
      Aurora-A kinase-dead mutant provoked defective migration of cortical neurons.
      Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule
      modulation in migrating neurons. Interestingly, suppression of CDK5 by an
      inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora
      A, which led to defective neuronal migration. We found that CDK5RAP2 is a key
      molecule that mediates functional interaction and is essential for centrosomal
      targeting of Aurora-A. Our observations demonstrated novel and surprising cross
      talk between Aurora-A and CDK5 during neuronal migration.

PMID- 22875940
TI  - Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid
      identity of a small region within the GluN1 amino terminal domain.
AB  - Anti-NMDA receptor (NMDAR) encephalitis is a newly identified autoimmune disorder
      that targets NMDARs, causing severe neurological symptoms including
      hallucinations, psychosis, and seizures, and may result in death (Dalmau et al.,
      2008). However, the exact epitope to which these antibodies bind is unknown. A
      clearly defined antigenic region could provide more precise testing, allow for
      comparison of immunogenicity between patients to explore potential clinically
      relevant variations, elucidate the functional effects of antibodies, and make
      patients' antibodies a more effective tool with which to study NMDAR function.
      Here, we use human CSF to explore the antigenic region of the NMDAR. We created a
      series of mutants within the amino terminal domain of GluN1 that change patient
      antibody binding in transfected cells in stereotyped ways. These mutants
      demonstrate that the N368/G369 region of GluN1 is crucial for the creation of
      immunoreactivity. Mass spectrometry experiments show that N368 is glycosylated in
      transfected cells and rat brain regions; however, this glycosylation is not
      directly required for epitope formation. Mutations of residues N368/G369 change
      the closed time of the receptor in single channel recordings; more frequent
      channel openings correlates with the degree of antibody staining, and acute
      antibody exposure prolongs open time of the receptor. The staining pattern of
      mutant receptors is similar across subgroups of patients, indicating consistent
      immunogenicity, although we have identified one region that has a variable role
      in epitope formation. These findings provide tools for detailed comparison of
      antibodies across patients and suggest an interaction between antibody binding
      and channel function.

PMID- 22875939
TI  - Enhanced NMDA receptor-dependent thalamic excitation and network oscillations in
      stargazer mice.
AB  - Disturbances in corticothalamic circuitry can lead to absence epilepsy. The
      reticular thalamic nucleus (RTN) plays a pivotal role in that it receives
      excitation from cortex and thalamus and, when strongly activated, can generate
      excessive inhibitory output and epileptic thalamocortical oscillations that
      depend on postinhibitory rebound. Stargazer (stg) mice have prominent absence
      seizures resulting from a mutant form of the AMPAR auxiliary protein stargazin.
      Reduced AMPAR excitation in RTN has been demonstrated previously in stg, yet the
      mechanisms leading from RTN hypoexcitation to epilepsy are unknown and unexpected
      because thalamic epileptiform oscillatory activity requires AMPARs. We
      demonstrate hyperexcitability in stg thalamic slices and further characterize the
      various excitatory inputs to RTN using electrical stimulation and laser scanning
      photostimulation. Patch-clamp recordings of spontaneous and evoked EPSCs in RTN
      neurons demonstrate reduced amplitude and increased duration of the AMPAR
      component with an increased amplitude NMDAR component. Short 200 Hz stimulus
      trains evoked a gradual approximately threefold increase in NMDAR EPSCs compared
      with single stimuli in wild-type (WT), indicating progressive NMDAR recruitment,
      whereas in stg cells, NMDAR responses were nearly maximal with single stimuli.
      Array tomography revealed lower synaptic, but higher perisynaptic, AMPAR density
      in stg RTN. Increasing NMDAR activity via reduced [Mg2+]o in WT phenocopied the
      thalamic hyperexcitability observed in stg, whereas changing [Mg2+]o had no
      effect on stg slices. These findings suggest that, in stg, a trafficking defect
      in synaptic AMPARs in RTN cells leads to a compensatory increase in synaptic
      NMDARs and enhanced thalamic excitability.

PMID- 22875941
TI  - Formation of Golgi-derived active zone precursor vesicles.
AB  - Vesicular trafficking of presynaptic and postsynaptic components is emerging as a
      general cellular mechanism for the delivery of scaffold proteins, ion channels,
      and receptors to nascent and mature synapses. However, the molecular mechanisms
      leading to the selection of cargos and their differential transport to
      subneuronal compartments are not well understood, in part because of the mixing
      of cargos at the plasma membrane and/or within endosomal compartments. In the
      present study, we have explored the cellular mechanisms of active zone precursor
      vesicle assembly at the Golgi in dissociated hippocampal neurons of Rattus
      norvegicus. Our studies show that Piccolo, Bassoon, and ELKS2/CAST exit the trans
      Golgi network on a common vesicle that requires Piccolo and Bassoon for its
      proper assembly. In contrast, Munc13 and synaptic vesicle proteins use distinct
      sets of Golgi-derived transport vesicles, while RIM1alpha associates with
      vesicular membranes in a post-Golgi compartment. Furthermore, Piccolo and Bassoon
      are necessary for ELKS2/CAST to leave the Golgi in association with vesicles, and
      a core domain of Bassoon is sufficient to facilitate formation of these vesicles.
      While these findings support emerging principles regarding active zone
      differentiation, the cellular and molecular analyses reported here also indicate
      that the Piccolo-Bassoon transport vesicles leaving the Golgi may undergo further
      changes in protein composition before arriving at synaptic sites.

PMID- 22875942
TI  - Methylene blue modulates huntingtin aggregation intermediates and is protective
      in Huntington's disease models.
AB  - Huntington's disease (HD) is a devastating neurodegenerative disorder with no
      disease-modifying treatments available. The disease is caused by expansion of a
      CAG trinucleotide repeat and manifests with progressive motor abnormalities,
      psychiatric symptoms, and cognitive decline. Expression of an expanded
      polyglutamine repeat within the Huntingtin (Htt) protein impacts numerous
      cellular processes, including protein folding and clearance. A hallmark of the
      disease is the progressive formation of inclusions that represent the culmination
      of a complex aggregation process. Methylene blue (MB), has been shown to modulate
      aggregation of amyloidogenic disease proteins. We investigated whether MB could
      impact mutant Htt-mediated aggregation and neurotoxicity. MB inhibited
      recombinant protein aggregation in vitro, even when added to preformed oligomers
      and fibrils. MB also decreased oligomer number and size and decreased
      accumulation of insoluble mutant Htt in cells. In functional assays, MB increased
      survival of primary cortical neurons transduced with mutant Htt, reduced
      neurodegeneration and aggregation in a Drosophila melanogaster model of HD, and
      reduced disease phenotypes in R6/2 HD modeled mice. Furthermore, MB treatment
      also promoted an increase in levels of BDNF RNA and protein in vivo. Thus, MB,
      which is well tolerated and used in humans, has therapeutic potential for HD.

PMID- 22875943
TI  - Long-range parallel processing and local recurrent activity in the visual cortex
      of the mouse.
AB  - The transfer of visual information from the primary visual cortex (V1) to higher
      order visual cortices is an essential step in visual processing. However, the
      dynamics of activation of visual cortices is poorly understood. In mice, several
      extrastriate areas surrounding V1 have been described. Using voltage-sensitive
      dye imaging in vivo, we determined the spatiotemporal dynamics of the activity
      evoked in the visual cortex by simple stimuli. Independently of precise areal
      boundaries, we found that V1 activation is rapidly followed by the depolarization
      of three functional groups of higher order visual areas organized
      retinotopically. After this sequential activation, all four regions were
      simultaneously active for most of the response. Concomitantly with the parallel
      processing of the visual input, the activity initiated retinotopically and
      propagated quickly and isotropically within each region. The size of this
      activation by local recurrent activity, which extended beyond the initial
      retinotopic response, was dependent on the intensity of the stimulus. Moreover
      the difference in the spatiotemporal dynamic of the response to dark and bright
      stimuli suggested the dominance in the mouse of the ON pathway. Our results
      suggest that the cortex integrates visual information simultaneously through
      across-area parallel and within-area serial processing.

PMID- 22875944
TI  - Tonic inhibition enhances fidelity of sensory information transmission in the
      cerebellar cortex.
AB  - Tonic inhibition is a key regulator of neuronal excitability and network function
      in the brain, but its role in sensory information processing remains poorly
      understood. The cerebellum is a favorable model system for addressing this
      question as granule cells, which form the input layer of the cerebellar cortex,
      permit high-resolution patch-clamp recordings in vivo, and are the only neurons
      in the cerebellar cortex that express the alpha6delta-containing GABA(A)
      receptors mediating tonic inhibition. We investigated how tonic inhibition
      regulates sensory information transmission in the rat cerebellum by using a
      combination of intracellular recordings from granule cells and molecular layer
      interneurons in vivo, selective pharmacology, and in vitro dynamic clamp
      experiments. We show that blocking tonic inhibition significantly increases the
      spontaneous firing rate of granule cells while only moderately increasing sensory
      evoked spike output. In contrast, enhancing tonic inhibition reduces the spike
      probability in response to sensory stimulation with minimal effect on the
      spontaneous spike rate. Both manipulations result in a reduction in the signal-to
      noise ratio of sensory transmission in granule cells and of parallel fiber
      synaptic input to downstream molecular layer interneurons. These results suggest
      that under basal conditions the level of tonic inhibition in vivo enhances the
      fidelity of sensory information transmission through the input layer of the
      cerebellar cortex.

PMID- 22875946
TI  - Risk assessment of fragility fractures: summary of NICE guidance.

PMID- 22875945
TI  - Rabconnectin3alpha promotes stable activity of the H+ pump on synaptic vesicles
      in hair cells.
AB  - Acidification of synaptic vesicles relies on the vacuolar-type ATPase (V-ATPase)
      and provides the electrochemical driving force for neurotransmitter exchange. The
      regulatory mechanisms that ensure assembly of the V-ATPase holoenzyme on synaptic
      vesicles are unknown. Rabconnectin3alpha (Rbc3alpha) is a potential candidate for
      regulation of V-ATPase activity because of its association with synaptic vesicles
      and its requirement for acidification of intracellular compartments. Here, we
      provide the first evidence for a role of Rbc3alpha in synaptic vesicle
      acidification and neurotransmission. In this study, we characterized mutant
      alleles of rbc3alpha isolated from a large-scale screen for zebrafish with
      auditory/vestibular defects. We show that Rbc3alpha is localized to basal regions
      of hair cells in which synaptic vesicles are present. To determine whether
      Rbc3alpha regulates V-ATPase activity, we examined the acidification of synaptic
      vesicles and localization of the V-ATPase in hair cells. In contrast to wild-type
      hair cells, we observed that synaptic vesicles had elevated pH, and a cytosolic
      subunit of the V-ATPase was no longer enriched in synaptic regions of mutant hair
      cells. As a consequence of defective acidification of synaptic vesicles, afferent
      neurons in rbc3alpha mutants had reduced firing rates and reduced accuracy of
      phase-locked action potentials in response to mechanical stimulation of hair
      cells. Collectively, our data suggest that Rbc3alpha modulates synaptic
      transmission in hair cells by promoting V-ATPase activity in synaptic vesicles.

PMID- 22875948
TI  - Promoting health equity.

PMID- 22875947
TI  - Effectiveness of rotavirus vaccination in prevention of hospital admissions for
      rotavirus gastroenteritis among young children in Belgium: case-control study.
AB  - OBJECTIVE: To evaluate the effectiveness of rotavirus vaccination among young
      children in Belgium. DESIGN: Prospective case-control study. SETTING: Random
      sample of 39 Belgian hospitals, February 2008 to June 2010. PARTICIPANTS: 215
      children admitted to hospital with rotavirus gastroenteritis confirmed by
      polymerase chain reaction and 276 age and hospital matched controls. All children
      were of an eligible age to have received rotavirus vaccination (that is, born
      after 1 October 2006 and aged >= 14 weeks). MAIN OUTCOME MEASURE: Vaccination
      status of children admitted to hospital with rotavirus gastroenteritis and
      matched controls. RESULTS: 99 children (48%) admitted with rotavirus
      gastroenteritis and 244 (91%) controls had received at least one dose of any
      rotavirus vaccine (P<0.001). The monovalent rotavirus vaccine accounted for 92%
      (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome,
      the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was
      90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children
      aged 3-11 months, and 90% (76% to 96%) in those aged >= 12 months. The G2P[4]
      genotype accounted for 52% of cases confirmed by polymerase chain reaction with
      eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against
      G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by
      polymerase chain reaction with eligible matched controls, there was reported co
      infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness
      against co-infected cases was 86% (52% to 96%). Effectiveness of at least one
      dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to
      95%). CONCLUSIONS: Rotavirus vaccination is effective for the prevention of
      admission to hospital for rotavirus gastroenteritis among young children in
      Belgium, despite the high prevalence of G2P[4] and viral co-infection.

PMID- 22875949
TI  - Diagnosis and management of lower limb peripheral arterial disease: summary of
      NICE guidance.

PMID- 22875952
TI  - What is good medicine?

PMID- 22875950
TI  - Migraine and cognitive decline among women: prospective cohort study.
AB  - OBJECTIVE: To evaluate the association between migraine and cognitive decline
      among women. DESIGN: Prospective cohort study. SETTING: Women's Health Study,
      United States. PARTICIPANTS: 6349 women aged 65 or older enrolled in the Women's
      Health Study who provided information about migraine status at baseline and
      participated in cognitive testing during follow-up. Participants were classified
      into four groups: no history of migraine, migraine with aura, migraine without
      aura, and past history of migraine (reports of migraine history but no migraine
      in the year prior to baseline). MAIN OUTCOME MEASURES: Cognitive testing was
      carried out at two year intervals up to three times using the telephone interview
      for cognitive status, immediate and delayed recall trials of the east Boston
      memory test, delayed recall trial of the telephone interview for cognitive status
      10 word list, and a category fluency test. All tests were combined into a global
      cognitive score, and tests assessing verbal memory were combined to create a
      verbal memory score. RESULTS: Of the 6349 women, 853 (13.4%) reported any
      migraine; of these, 195 (22.9%) reported migraine with aura, 248 (29.1%) migraine
      without aura, and 410 (48.1%) a past history of migraine. Compared with women
      with no history of migraine, those who experienced migraine with or without aura
      or had a past history of migraine did not have significantly different rates of
      cognitive decline in any of the cognitive scores: values for the rate of change
      of the global cognitive score between baseline and the last observation ranged
      from -0.01 (SE 0.04) for past history of migraine to 0.08 (SE 0.04) for migraine
      with aura when compared with women without any history of migraine. Women who
      experienced migraine were also not at increased risk of substantial cognitive
      decline (worst 10% of the distribution of decline). When compared with women
      without a history of migraine, the relative risks for the global score ranged
      from 0.77 (95% confidence interval 0.46 to 1.28) for women with migraine without
      aura to 1.17 (0.84 to 1.63) for women with a past history of migraine.
      CONCLUSION: In this prospective cohort of women, migraine status was not
      associated with faster rates of cognitive decline.

PMID- 22875951
TI  - Management of lower urinary tract dysfunction in neurological disease: summary of
      NICE guidance.

PMID- 22875953
TI  - Ensuring open access for publicly funded research.

PMID- 22875954
TI  - Rotavirus vaccination programmes.

PMID- 22875955
TI  - A national early warning score for acutely ill patients.

PMID- 22875956
TI  - A jab in the dark.

PMID- 22875959
TI  - Why are the media so soft on Circle?

PMID- 22875960
TI  - Profit is not a dirty word.

PMID- 22875961
TI  - Expression of LH receptor in nonpregnant mouse endometrium: LH induction of 3beta
      HSD and de novo synthesis of progesterone.
AB  - In mouse uterus, at the late diestrus stage LH binding sites have previously been
      described. The aim of our study was to confirm the existence of LH receptor (Lhr
      (Lhcgr)) mRNA and its protein in mouse endometrium. Endometrium at all stages of
      the estrous cycle contained Lhr mRNA, essentially identical to that found in
      mouse ovary. Endometrium also contained a 72  kDa immunoreactive receptor protein
      that bound to mouse anti-LHR antibody in western blot. Both receptor mRNA and
      protein were maximally expressed in the endometrium at metestrus and LH caused a
      significant increase in their expression levels. Endometrium also contained 3beta
      hydroxy steroid dehydrogenase (3beta-hsd) mRNA and 3beta-HSD protein. LH addition
      elevated their expression and activity as evident from increased conversion of
      labeled pregnenolone to progesterone (P(4)) and de novo P(4) synthesis. LH
      induced endometrial P(4) synthesis is mediated through expression of
      steroidogenic acute regulatory (Star) gene. Results demonstrated that LH-induced
      P(4) synthesis in endometrium is possibly mediated through the cAMP pathway.
      Involvement of a MAPK pathway was also evident. Gonadotropin-stimulated
      endometrial P(4) synthesis was markedly attenuated by an antagonist of MEK1/2,
      PD98059. LH-stimulated MEK1/2-dependent phosphorylation of ERK1/2 in a
      concentration- and time-dependant manner in cultured endometrial tissues.
      Moreover, involvement of cAMP in LH-stimulated activation of ERK1/2 was also
      evident. It is therefore possible that the major signaling pathways regulating
      endometrial steroidogenesis in mouse, including the adenylate cyclase and MAP
      kinase pathways, converge at a point distal to activation of protein kinase A and
      ERK1/2.

PMID- 22875962
TI  - Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and
      pituitary of rats associated with resistance to leptin acute anorectic action.
AB  - Leptin has been shown to regulate the hypothalamus-pituitary-thyroid axis, acting
      primarily through the STAT3 pathway triggered through the binding of leptin to
      the long-chain isoform of the leptin receptor, ObRb. We previously demonstrated
      that although hyperthyroid rats presented leptin effects on TSH secretion, those
      effects were abolished in hypothyroid rats. We addressed the hypothesis that
      changes in the STAT3 pathway might explain the lack of TSH response to leptin in
      hypothyroidism by evaluating the protein content of components of leptin
      signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid
      (0.03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5
      MUg/100 g body weight /5 days) rats. Hypothyroid rats exhibited decreased ObRb
      and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the
      pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3
      (P<0.05). Except for a modest decrease in pituitary STAT3, no other alterations
      were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the
      hypothyroid rats did not exhibit a reduction in food ingestion after a single
      injection of leptin (0.5 mg/kg body weight). Therefore, hypothyroidism decreased
      ObRb-STAT3 signalling in the hypothalamus and pituitary gland, which likely
      contributes to the loss of leptin action on food intake and TSH secretion, as
      previously observed in hypothyroid rats.

PMID- 22875963
TI  - HIV-1 neutralizing antibodies display dual recognition of the primary and
      coreceptor binding sites and preferential binding to fully cleaved envelope
      glycoproteins.
AB  - The gp120 CD4 binding site (CD4bs) and coreceptor binding site (CoRbs) are two
      functionally conserved elements of the HIV-1 envelope glycoproteins (Env). We
      previously defined the presence of CD4bs-neutralizing antibodies in the serum of
      an HIV-1-infected individual and subsequently isolated the CD4bs-specific
      monoclonal antibodies (MAbs) VRC01 and VRC03 from the memory B cell population.
      Since this donor's serum also appeared to contain neutralizing antibodies to the
      CoRbs, we employed a differential fluorescence-activated cell sorter (FACS)-based
      sorting strategy using an Env trimer possessing a CoRbs knockout mutation (I420R)
      to isolate specific B cells. The MAb VRC06 was recovered from these cells, and
      its genetic sequence allowed us to identify a clonal relative termed VRC06b,
      which was isolated from a prior cell sort using a resurfaced core gp120 probe and
      its cognate CD4bs knockout mutant. VRC06 and VRC06b neutralized 22% and 44% of
      viruses tested, respectively. Epitope mapping studies revealed that the two MAbs
      were sensitive to mutations in both the gp120 CoRbs and the CD4bs and could cross
      block binding of both CD4bs and CoRbs MAbs to gp120. Fine mapping indicated
      contacts within the gp120 bridging sheet and the base of the third major variable
      region (V3), which are elements of the CoRbs. Cell surface binding assays
      demonstrated preferential recognition of fully cleaved Env trimers over uncleaved
      trimers. Thus, VRC06 and VRC06b are Env trimer precursor cleavage-sensitive
      neutralizing MAbs that bind to a region of gp120 that overlaps both the primary
      and the secondary HIV-1 receptor binding sites.

PMID- 22875964
TI  - Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus
      nucleocapsid protein.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne virus of
      the Bunyaviridae family that is responsible for a fatal human disease for which
      preventative or therapeutic measures do not exist. We solved the crystal
      structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential
      therapeutic target, at a resolution of 2.1 A. N comprises a large globular domain
      composed of both N- and C-terminal sequences, likely involved in RNA binding, and
      a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its
      apex. Alignment of our structure with that of the recently reported N protein
      from strain YL04057 shows a close correspondence of all folds but significant
      transposition of the arm through a rotation of 180 degrees and a translation of
      40 A. These observations suggest a structural flexibility that may provide the
      basis for switching between alternative N protein conformations during important
      functions such as RNA binding and oligomerization. Our structure reveals surfaces
      likely involved in RNA binding and oligomerization, and functionally critical
      residues within these domains were identified using a minigenome system able to
      recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the
      polypeptide chain at the exposed DEVD motif; however, the cleaved N protein
      remains an intact unit, likely due to the intimate association of N- and C
      terminal fragments in the globular domain. Structural alignment with existing N
      proteins reveals that the closest CCHFV relative is not another bunyavirus but
      the arenavirus Lassa virus instead, suggesting that current segmented negative
      strand RNA virus taxonomy may need revision.

PMID- 22875965
TI  - The pre-NH(2)-terminal domain of the herpes simplex virus 1 DNA polymerase
      catalytic subunit is required for efficient viral replication.
AB  - The catalytic subunit of herpes simplex virus 1 DNA polymerase (HSV-1 Pol) has
      been extensively studied; however, its full complement of functional domains has
      yet to be characterized. A crystal structure has revealed a previously
      uncharacterized pre-NH(2)-terminal domain (residues 1 to 140) within HSV-1 Pol.
      Due to the conservation of the pre-NH(2)-terminal domain within the herpesvirus
      Pol family and its location in the crystal structure, we hypothesized that this
      domain provides an important function during viral replication in the infected
      cell distinct from 5'-3' polymerase activity. We identified three pre-NH(2)
      terminal Pol mutants that exhibited 5'-3' polymerase activity indistinguishable
      from that of wild-type Pol in vitro: deletion mutants PolDeltaN43 and PolDeltaN52
      that lack the extreme N-terminal 42 and 51 residues, respectively, and mutant
      PolA(6), in which a conserved motif at residues 44 to 49 was replaced with
      alanines. We constructed the corresponding pol mutant viruses and found that the
      polDeltaN43 mutant displayed replication kinetics similar to those of wild-type
      virus, while polDeltaN52 and polA(6) mutant virus infection resulted in an 8-fold
      defect in viral yield compared to that achieved with wild type and their
      respective rescued derivative viruses. Additionally, both polDeltaN52 and polA(6)
      viruses exhibited defects in viral DNA synthesis that correlated with the
      observed reduction in viral yield. These results strongly indicate that the
      conserved motif within the pre-NH(2)-terminal domain is important for viral DNA
      synthesis and production of infectious virus and indicate a functional role for
      this domain.

PMID- 22875966
TI  - Visualizing production of beta interferon by astrocytes and microglia in brain of
      La Crosse virus-infected mice.
AB  - Beta interferon (IFN-beta) is a major component of innate immunity in mammals,
      but information on the in vivo source of this cytokine after pathogen infection
      is still scarce. To identify the cell types responsible for IFN-beta production
      during viral encephalitis, we used reporter mice that express firefly luciferase
      under the control of the IFN-beta promoter and stained organ sections with
      luciferase-specific antibodies. Numerous luciferase-positive cells were detected
      in regions of La Crosse virus (LACV)-infected mouse brains that contained many
      infected cells. Double-staining experiments with cell-type-specific markers
      revealed that similar numbers of astrocytes and microglia of infected brains were
      luciferase positive, whereas virus-infected neurons rarely contained detectable
      levels of luciferase. Interestingly, if a mutant LACV unable of synthesizing the
      IFN-antagonistic factor NSs was used for challenge, the vast majority of the IFN
      beta-producing cells in infected brains were astrocytes rather than microglia.
      Similar conclusions were reached in a second series of experiments in which
      conditional reporter mice expressing the luciferase reporter gene solely in
      defined cell types were infected with wild-type or mutant LACV. Collectively, our
      data suggest that glial cells rather than infected neurons represent the major
      source of IFN-beta in LACV-infected mouse brains. They further indicate that IFN
      beta synthesis in astrocytes and microglia is differentially affected by the
      viral IFN antagonist, presumably due to differences in LACV susceptibility of
      these two cell types.

PMID- 22875967
TI  - Herpes simplex virus 1 ubiquitin ligase ICP0 interacts with PML isoform I and
      induces its SUMO-independent degradation.
AB  - Herpes simplex virus 1 (HSV-1) immediate-early protein ICP0 localizes to cellular
      structures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10
      and disrupts their integrity by inducing the degradation of PML. There are six
      PML isoforms with different C-terminal regions in ND10, of which PML isoform I
      (PML.I) is the most abundant. Depletion of all PML isoforms increases the plaque
      formation efficiency of ICP0-null mutant HSV-1, and reconstitution of expression
      of PML.I and PML.II partially reverses this improved replication. ICP0 also
      induces widespread degradation of SUMO-conjugated proteins during HSV-1
      infection, and this activity is linked to its ability to counteract cellular
      intrinsic antiviral resistance. All PML isoforms are highly SUMO modified, and
      all such modified forms are sensitive to ICP0-mediated degradation. However, in
      contrast to the situation with the other isoforms, ICP0 also targets PML.I that
      is not modified by SUMO, and PML in general is degraded more rapidly than the
      bulk of other SUMO-modified proteins. We report here that ICP0 interacts with
      PML.I in both yeast two-hybrid and coimmunoprecipitation assays. This interaction
      is dependent on PML.I isoform-specific sequences and the N-terminal half of ICP0
      and is required for SUMO-modification-independent degradation of PML.I by ICP0.
      Degradation of the other PML isoforms by ICP0 was less efficient in cells
      specifically depleted of PML.I. Therefore, ICP0 has two distinct mechanisms of
      targeting PML: one dependent on SUMO modification and the other via SUMO
      independent interaction with PML.I. We conclude that the ICP0-PML.I interaction
      reflects a countermeasure to PML-related antiviral restriction.

PMID- 22875968
TI  - A quantitative measurement of antiviral activity of anti-human immunodeficiency
      virus type 1 drugs against simian immunodeficiency virus infection: dose-response
      curve slope strongly influences class-specific inhibitory potential.
AB  - Simian immunodeficiency virus (SIV) infection in macaques is so far the best
      animal model for human immunodeficiency virus type 1 (HIV-1) studies, but
      suppressing viral replication in infected animals remains challenging. Using a
      novel single-round infectivity assay, we quantitated the antiviral activities of
      antiretroviral drugs against SIV. Our results emphasize the importance of the
      dose-response curve slope in determining the inhibitory potential of
      antiretroviral drugs and provide useful information for regimen selection in
      treating SIV-infected animals in models of therapy and virus eradication.

PMID- 22875969
TI  - Acute cytomegalovirus infection is associated with increased frequencies of
      activated and apoptosis-vulnerable T cells in HIV-1-infected infants.
AB  - Cytomegalovirus (CMV) coinfection is associated with infant HIV-1 disease
      progression and mortality. In a cohort of Kenyan HIV-infected infants, the
      frequencies of activated (CD38(+) HLA-DR(+)) and apoptosis-vulnerable (CD95(+)
      Bcl-2(-)) CD4(+) and CD8(+) T cells increased substantially during acute CMV
      infection. The frequency of activated CD4(+) T cells was strongly associated with
      both concurrent CMV coinfection (P = 0.001) and HIV-1 viral load (P = 0.05). The
      frequency of apoptosis-vulnerable cells was also associated with CMV coinfection
      in the CD4 (P = 0.02) and CD8 (P < 0.001) T cell subsets. Similar observations
      were made in HIV-exposed uninfected infants. CMV-induced increases in T cell
      activation and apoptosis may contribute to the rapid disease progression in
      coinfected infants.

PMID- 22875970
TI  - Second-site mutations selected in transcriptional regulatory sequences compensate
      for engineered mutations in the vesicular stomatitis virus nucleocapsid protein.
AB  - The active template for RNA synthesis for vesicular stomatitis virus (VSV) and
      other negative-strand viruses is the RNA genome in association with the
      nucleocapsid (N) protein. The N protein molecules sequester the genomic RNA and
      are linked together by a network of noncovalent interactions. We previously
      demonstrated that mutations predicted to weaken interactions between adjacent N
      protein molecules altered the levels of RNA synthesis directed from subgenomic
      ribonucleoprotein (RNP) templates. To determine if these mutations affect virus
      replication, recombinant viruses containing single-amino-acid substitutions in
      the N protein were recovered. Four mutations altered transcription and genome
      replication levels, perturbed viral protein synthesis, and inhibited virus
      replication. Selective pressure for improved virus replication was applied by
      eight sequential passages. After five passages, virus replication improved and
      RNA synthesis recovered concomitantly with the restoration of the protein molar
      ratios to near-wild-type levels. Genome sequences were compared before and after
      passage to determine whether compensatory mutations were selected and to
      potentially identify interactions between N protein molecules or between the RNP
      template and the viral polymerase. Improved virus replication correlated with the
      selection of additional mutations located in cis-acting transcriptional
      regulatory sequences at the gene junctions of the genome rather than in coding
      sequences, with one exception. The engineered N gene mutations perturbed mRNA and
      protein expression levels, but the selection of modified transcriptional
      regulatory sequences with passage facilitated the restoration of wild-type
      protein expression by modulating transcription levels, reflecting the
      adaptability and versatility of gene regulation by transcriptional control.

PMID- 22875971
TI  - Filamentous influenza virus enters cells via macropinocytosis.
AB  - Influenza virus is pleiomorphic, producing both spherical (100-nm-diameter) and
      filamentous (100-nm by 20-MUm) virions. While the spherical virions are known to
      enter host cells through exploitation of clathrin-mediated endocytosis, the entry
      pathway for filamentous virions has not been determined, though the existence of
      an alternative, non-clathrin-, non-caveolin-mediated entry pathway for influenza
      virus has been known for many years. In this study, we confirm recent results
      showing that influenza virus utilizes macropinocytosis as an alternate entry
      pathway. Furthermore, we find that filamentous influenza viruses use
      macropinocytosis as the primary entry mechanism. Virions enter cells as intact
      filaments within macropinosomes and are trafficked to the acidic late-endosomal
      compartment. Low pH triggers a conformational change in the M2 ion channel
      protein, altering membrane curvature and leading to a fragmentation of the
      filamentous virions. This fragmentation may enable more-efficient fusion between
      the viral and endosomal membranes.

PMID- 22875972
TI  - Vaccinia virus virion membrane biogenesis protein A11 associates with viral
      membranes in a manner that requires the expression of another membrane biogenesis
      protein, A6.
AB  - A group of vaccinia virus (VACV) proteins, including A11, L2, and A6, are
      required for biogenesis of the primary envelope of VACV, specifically, for the
      acquisition of viral membrane precursors. However, the interconnection among
      these proteins is unknown and, with the exception of L2, the connection of these
      proteins with membranes is also unknown. In this study, prompted by the findings
      that A6 coprecipitated A11 and that the cellular distribution of A11 was
      dramatically altered by repression of A6 expression, we studied the localization
      of A11 in cells by using immunofluorescence and cell fractionation analysis. A11
      was found to associate with membranes and colocalize with virion membrane
      proteins in viral replication factories during normal VACV replication. A11
      partitioned almost equally between the detergent and aqueous phases upon Triton X
      114 phase separation, demonstrating an intrinsic affinity with lipids. However,
      in the absence of infection or VACV late protein synthesis, A11 did not associate
      with cellular membranes. Furthermore, when A6 expression was repressed, A11 did
      not colocalize with any viral membrane proteins or associate with membranes. In
      contrast, when virion envelope formation was blocked at a later step by
      repression of A14 expression or by rifampin treatment, A11 colocalized with
      virion membrane proteins in the factories. Altogether, our data showed that A11
      associates with viral membranes during VACV replication, and this association
      requires A6 expression. This study provides a physical connection between A11 and
      viral membranes and suggests that A6 regulates A11 membrane association.

PMID- 22875973
TI  - Role of interferon regulatory factor 7 in T cell responses during acute
      lymphocytic choriomeningitis virus infection.
AB  - Type I interferons (IFNs), predominantly IFN-alpha and -beta, play critical roles
      in both innate and adaptive immune responses against viral infections. Interferon
      regulatory factor 7 (IRF7), a key innate immune molecule in the type I IFN
      signaling pathway, is essential for the type I IFN response to many viruses,
      including lymphocytic choriomeningitis virus (LCMV). Here, we show that although
      IRF7 knockout (KO) mice failed to control the replication of LCMV in the early
      stages of infection, they were capable of clearing LCMV infection. Despite the
      lack of type I IFN production, IRF7 KO mice generated normal CD4(+) T cell
      responses, and the expansion of naive CD8(+) T cells into primary CD8(+) T cells
      specific for LCMV GP(33-41) was relatively normal. In contrast, the expansion of
      the LCMV NP(396)-specific CD8(+) T cells was severely impaired in IRF7 KO mice.
      We demonstrated that this defective CD8(+) T cell response is due neither to an
      impaired antigen-presenting system nor to any intrinsic role of IRF7 in CD8(+) T
      cells. The lack of a type I IFN response in IRF7 KO mice did not affect the
      formation of memory CD8(+) T cells. Thus, the present study provides new insight
      into the impact of the innate immune system on viral pathogenesis and
      demonstrates the critical contribution of innate immunity in controlling virus
      replication in the early stages of infection, which may shape the quality of
      CD8(+) T cell responses.

PMID- 22875974
TI  - Arenavirus infection induces discrete cytosolic structures for RNA replication.
AB  - Arenaviruses are responsible for acute hemorrhagic fevers with high mortality and
      pose significant threats to public health and biodefense. These enveloped
      negative-sense RNA viruses replicate in the cell cytoplasm and express four
      proteins. To better understand how these proteins insinuate themselves into
      cellular processes to orchestrate productive viral replication, we have
      identified and characterized novel cytosolic structures involved in arenavirus
      replication and transcription. In cells infected with the nonpathogenic Tacaribe
      virus or the attenuated Candid#1 strain of Junin virus, we find that newly
      synthesized viral RNAs localize to cytosolic puncta containing the nucleoprotein
      (N) of the virus. Density gradient centrifugation studies reveal that these
      replication-transcription complexes (RTCs) are associated with cellular membranes
      and contain full-length genomic- and antigenomic-sense RNAs. Viral mRNAs
      segregate at a higher buoyant density and are likewise scant in immunopurified
      RTCs, consistent with their translation on bulk cellular ribosomes. In addition,
      confocal microscopy analysis reveals that RTCs contain the lipid
      phosphatidylinositol-4-phosphate and proteins involved in cellular mRNA
      metabolism, including the large and small ribosomal subunit proteins L10a and S6,
      the stress granule protein G3BP1, and a subset of translation initiation factors.
      Elucidating the structure and function of RTCs will enhance our understanding of
      virus-cell interactions that promote arenavirus replication and mitigate against
      host cell immunity. This knowledge may lead to novel intervention strategies to
      limit viral virulence and pathogenesis.

PMID- 22875975
TI  - Herpes simplex virus 1 DNA is in unstable nucleosomes throughout the lytic
      infection cycle, and the instability of the nucleosomes is independent of DNA
      replication.
AB  - Herpes simplex virus 1 (HSV-1) DNA is chromatinized during latency and
      consequently regularly digested by micrococcal nuclease (MCN) to nucleosome-size
      fragments. In contrast, MCN digests HSV-1 DNA in lytically infected cells to
      mostly heterogeneous sizes. Yet HSV-1 DNA coimmunoprecipitates with histones
      during lytic infections. We have shown that at 5 h postinfection, most nuclear
      HSV-1 DNA is in particularly unstable nucleoprotein complexes and consequently is
      more accessible to MCN than DNA in cellular chromatin. HSV-1 DNA was
      quantitatively recovered at this time in complexes with the biophysical
      properties of mono- to polynucleosomes following a modified MCN digestion
      developed to detect potential unstable intermediates. We proposed that most HSV-1
      DNA is in unstable nucleosome-like complexes during lytic infections.
      Physiologically, nucleosome assembly typically associates with DNA replication,
      although DNA replication transiently disrupts nucleosomes. It therefore remained
      unclear whether the instability of the HSV-1 nucleoprotein complexes was related
      to the ongoing viral DNA replication. Here we tested whether HSV-1 DNA is in
      unstable nucleosome-like complexes before, during, or after the peak of viral DNA
      replication or when HSV-1 DNA replication is inhibited. HSV-1 DNA was
      quantitatively recovered in complexes fractionating as mono- to polynucleosomes
      from nuclei harvested at 2, 5, 7, or 9 h after infection, even if viral DNA
      replication was inhibited. Therefore, most HSV-1 DNA is in unstable nucleosome
      like complexes throughout the lytic replication cycle, and the instability of
      these complexes is surprisingly independent of HSV-1 DNA replication. The
      specific accessibility of nuclear HSV-1 DNA, however, varied at different times
      after infection.

PMID- 22875976
TI  - Defective HIV-1 particle assembly in AP-3-deficient cells derived from patients
      with Hermansky-Pudlak syndrome type 2.
AB  - Adaptor protein complex 3 (AP-3) is a heterotetramer that is involved in signal
      mediated protein sorting to endosomal-lysosomal organelles. AP-3 deficiency in
      humans, induced by mutations in the AP3B1 gene, which encodes the beta3A subunit
      of the AP-3 complex, results in Hermansky-Pudlak syndrome 2 (HPS2), which is a
      rare genetic disorder with defective lysosome-related organelles. In a previous
      study, we identified the AP-3 complex as an important contributor to HIV-1
      assembly and release. We hypothesized that cells from patients affected by HPS2
      should demonstrate abnormalities of HIV-1 assembly. Here we report that HIV-1
      particle assembly and release are indeed diminished in HPS2 fibroblast cultures.
      Transient or stable expression of the full-length wild-type beta3A subunit in
      HPS2 fibroblasts restored the impaired virus assembly and release. In contrast,
      virus-like particle release mediated by MA-deficient Gag mutants lacking the AP-3
      binding site was not altered in HPS2 cells, indicating that the MA domain serves
      as the major viral determinant required for the recruitment of the AP-3 complex.
      AP-3 deficiency decreased HIV-1 Gag localization at the plasma membrane and late
      endosomes and increased the accumulation of HIV-1 Gag at an intermediate step
      between early and late endosomes. Blockage of the clathrin-mediated endocytic
      pathway in HPS2 cells did not reverse the inhibited virus assembly and release
      imposed by the AP-3 deficiency. These results demonstrate that the intact and
      stable AP-3 complex is required for HIV-1 assembly and release, and the
      involvement of the AP-3 complex in late stages of the HIV-1 replication cycle is
      independent of clathrin-mediated endocytosis.

PMID- 22875978
TI  - Licenced to transplant: UK overkill on EU Organ Directive provides golden
      opportunity for research.
AB  - Progress in transplantation outcomes depends on continuing research into both
      donor and recipient factors that may enhance graft and patient survival. A system
      of licencing for transplantation research, introduced by the Human Tissue Act
      2004, which separates it from the transplantation process (then exempt from
      licencing), has damaged this vital activity by a combination of inflexible
      interpretation of the 2004 Act and fear of criminal liability on the part of
      researchers. Now, following the European Union (EU) Directive (2010) on standards
      of quality and safety of human organs intended for transplantation, new UK
      Regulations have been drafted, which are intended to implement it. These
      Regulations impose a compulsory licencing system, similar to that for research,
      on the whole transplantation process. This goes beyond what is required by the
      Directive and may even have an inhibitory effect similar to that already seen in
      research. Initial draft Regulations went further, imposing criminal sanctions for
      breaches. However, following a public consultation process, the Department of
      Health (DH) has recently stated that, as a result of the overwhelming view of
      respondents that the proposed licencing system was unnecessary, all sanctions
      under the final Regulations are now decriminalised, with the sole exception of
      operating without a licence. While this does not eliminate the negative effect of
      licencing, it does suggest an awareness of the DH that excessive regulation
      unnecessarily harms the transplantation process. An opportunity thus arises for
      the Human Tissue Authority (the regulatory body for both the new licences and
      research licences under the 2004 Act) to end the current illogical and harmful
      separation of transplantation and transplantation research by ensuring that all
      centres licenced for organ donation, retrieval and transplantation are also fully
      licenced for related research.

PMID- 22875977
TI  - RNase L triggers autophagy in response to viral infections.
AB  - Autophagy is a programmed homeostatic response to diverse types of cellular
      stress that disposes of long-lived proteins, organelles, and invading microbes
      within double-membraned structures called autophagosomes. The 2',5'
      oligoadenylate/RNase L system is a virus-activated host RNase pathway that
      disposes of or processes viral and cellular single-stranded RNAs. Here we report
      that activation of RNase L during viral infections induces autophagy.
      Accordingly, infections with encephalomyocarditis virus or vesicular stomatitis
      virus led to higher levels of autophagy in wild-type mouse embryonic fibroblasts
      (MEF) than in RNase L-null MEF. Similarly, direct activation of RNase L with a
      2',5'-oligoadenylate resulted in p62(SQSTM1) degradation, LC3BI/LC3BII
      conversion, and appearance of autophagosomes. To determine the effect of RNase L
      mediated autophagy on viral replication, we compared viral yields in wild-type
      and RNase L-null MEF in the absence or presence of either chemical inhibitors of
      autophagy (bafilomycin A1 or 3-methyladenine) or small interfering RNA (siRNA)
      against ATG5 or beclin-1. At a low multiplicity of infection, induction of
      autophagy by RNase L during the initial cycle of virus growth contributed to the
      suppression of virus replication. However, in subsequent rounds of infection,
      autophagy promoted viral replication, reducing the antiviral effect of RNase L.
      Our results indicate a novel function of RNase L as an inducer of autophagy that
      affects viral yields.

PMID- 22875980
TI  - On the wrongness of killing.

PMID- 22875981
TI  - Supporting positive experiences and sustained participation in clinical trials:
      looking beyond information provision.
AB  - Recruitment processes for clinical trials are governed by guidelines and
      regulatory systems intended to ensure participation is informed and voluntary.
      Although the guidelines and systems provide some protection to potential
      participants, current recruitment processes often result in limited understanding
      and experiences of inadequate decision support. Many trials also have high drop
      out rates among participants, which are ethically troubling because they can be
      indicative of poor experiences and they limit the usefulness of the knowledge the
      trials were designed to generate. Drawing on recent social-psychological and
      philosophical-ethical research on trial recruitment and patient participation in
      treatment decision-making, this paper identifies possibilities for improving
      communicative support for both initial decisions and ongoing participation in
      clinical trials. It highlights the potential of a shift in thinking about
      'voluntariness', underpinned by relational understandings of autonomy, to
      encourage more nuanced judgements about the ethics of communication between trial
      staff and (potential) participants. The paper suggests that the idea of
      responsively enabling people to consider invitations or requests to participate
      in particular trials could serve as a general guide to communication. This might
      help ensure decisions about trial participation are meaningfully informed and
      voluntary, and that relationships between trial staff and participants contribute
      to positive experiences of trial participation and ultimately to the generation
      of the robust knowledge.

PMID- 22875983
TI  - Autoinhibition of the formin Cappuccino in the absence of canonical
      autoinhibitory domains.
AB  - Formins are a conserved family of proteins known to enhance actin polymerization.
      Most formins are regulated by an intramolecular interaction. The Drosophila
      formin, Cappuccino (Capu), was believed to be an exception. Capu does not contain
      conserved autoinhibitory domains and can be regulated by a second protein, Spire.
      We report here that Capu is, in fact, autoinhibited. The N-terminal half of Capu
      (Capu-NT) potently inhibits nucleation and binding to the barbed end of
      elongating filaments by the C-terminal half of Capu (Capu-CT). Hydrodynamic
      analysis indicates that Capu-NT is a dimer, similar to the N-termini of other
      formins. These data, combined with those from circular dichroism, suggest,
      however, that it is structurally distinct from previously described formin
      inhibitory domains. Finally, we find that Capu-NT binds to a site within Capu-CT
      that overlaps with the Spire-binding site, the Capu-tail. We propose models for
      the interaction between Spire and Capu in light of the fact that Capu can be
      regulated by autoinhibition.

PMID- 22875984
TI  - Multisite phosphorylation of oxysterol-binding protein regulates sterol binding
      and activation of sphingomyelin synthesis.
AB  - The endoplasmic reticulum (ER)-Golgi sterol transfer activity of oxysterol
      binding protein (OSBP) regulates sphingomyelin (SM) synthesis, as well as post
      Golgi cholesterol efflux pathways. The phosphorylation and ER-Golgi localization
      of OSBP are correlated, suggesting this modification regulates the directionality
      and/or specificity of transfer activity. In this paper, we report that
      phosphorylation on two serine-rich motifs, S381-S391 (site 1) and S192, S195,
      S200 (site 2), specifically controls OSBP activity at the ER. A phosphomimetic of
      the SM/cholesterol-sensitive phosphorylation site 1 (OSBP-S5E) had increased in
      vitro cholesterol and 25-hydroxycholesterol-binding capacity, and cholesterol
      extraction from liposomes, but reduced transfer activity. Phosphatidylinositol 4
      phosphate (PI(4)P) and cholesterol competed for a common binding site on OSBP;
      however, direct binding of PI(4)P was not affected by site 1 phosphorylation.
      Individual site 1 and site 2 phosphomutants supported oxysterol activation of SM
      synthesis in OSBP-deficient CHO cells. However, a double site1/2 mutant (OSBP
      S381A/S3D) was deficient in this activity and was constitutively colocalized with
      vesicle-associated membrane protein-associated protein A (VAP-A) in a collapsed
      ER network. This study identifies phosphorylation regulation of sterol and VAP-A
      binding by OSBP in the ER, and PI(4)P as an alternate ligand that could be
      exchanged for sterol in the Golgi apparatus.

PMID- 22875986
TI  - Combined computational and experimental analysis reveals mitogen-activated
      protein kinase-mediated feedback phosphorylation as a mechanism for signaling
      specificity.
AB  - Different environmental stimuli often use the same set of signaling proteins to
      achieve very different physiological outcomes. The mating and invasive growth
      pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade
      that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7
      activation of the MAP kinase Fus3, invasive growth requires activation of the
      alternate MAP kinase Kss1. To determine how MAP kinase specificity is achieved,
      we used a series of mathematical models to quantitatively characterize pheromone
      stimulated kinase activation. In accordance with the computational analysis, MAP
      kinase feedback phosphorylation of Ste7 results in diminished activation of Kss1,
      but not Fus3. These findings reveal how feedback phosphorylation of a common
      pathway component can limit the activity of a competing MAP kinase through
      feedback phosphorylation of a common activator, and thereby promote signal
      fidelity.

PMID- 22875985
TI  - Quiescent fibroblasts are protected from proteasome inhibition-mediated toxicity.
AB  - Proteasome inhibition is used as a treatment strategy for multiple types of
      cancers. Although proteasome inhibition can induce apoptotic cell death in
      actively proliferating cells, it is less effective in quiescent cells. In this
      study, we used primary human fibroblasts as a model system to explore the link
      between the proliferative state of a cell and proteasome inhibition-mediated cell
      death. We found that proliferating and quiescent fibroblasts have strikingly
      different responses to MG132, a proteasome inhibitor; proliferating cells rapidly
      apoptosed, whereas quiescent cells maintained viability. Moreover, MG132
      treatment of proliferating fibroblasts led to increased superoxide anion levels,
      juxtanuclear accumulation of ubiquitin- and p62/SQSTM1-positive protein
      aggregates, and apoptotic cell death, whereas MG132-treated quiescent cells
      displayed fewer juxtanuclear protein aggregates, less apoptosis, and higher
      levels of mitochondrial superoxide dismutase. In both cell states, reducing
      reactive oxygen species with N-acetylcysteine lessened protein aggregation and
      decreased apoptosis, suggesting that protein aggregation promotes apoptosis. In
      contrast, increasing cellular superoxide levels with 2-methoxyestradiol treatment
      or inhibition of autophagy/lysosomal pathways with bafilomycin A1 sensitized
      serum-starved quiescent cells to MG132-induced apoptosis. Thus, antioxidant
      defenses and the autophagy/lysosomal pathway protect serum-starved quiescent
      fibroblasts from proteasome inhibition-induced cytotoxicity.

PMID- 22875987
TI  - Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling
      cellular distribution of Like-Sm proteins.
AB  - Processing bodies (P-bodies) are dynamic cytoplasmic structures involved in mRNA
      degradation, but the mechanism that governs their formation is poorly understood.
      In this paper, we address a role of Like-Sm (LSm) proteins in formation of P
      bodies and provide evidence that depletion of nuclear LSm8 increases the number
      of P-bodies, while LSm8 overexpression leads to P-body loss. We show that LSm8
      knockdown causes relocalization of LSm4 and LSm6 proteins to the cytoplasm and
      suggest that LSm8 controls nuclear accumulation of all LSm2-7 proteins. We
      propose a model in which redistribution of LSm2-7 to the cytoplasm creates new
      binding sites for other P-body components and nucleates new, microscopically
      visible structures. The model is supported by prolonged residence of two P-body
      proteins, DDX6 and Ago2, in P-bodies after LSm8 depletion, which indicates
      stronger interactions between these proteins and P-bodies. Finally, an increased
      number of P-bodies has negligible effects on microRNA-mediated translation
      repression and nonsense mediated decay, further supporting the view that the
      function of proteins localized in P-bodies is independent of visible P-bodies.

PMID- 22875988
TI  - Coiled-coil networking shapes cell molecular machinery.
AB  - The highly abundant alpha-helical coiled-coil motif not only mediates crucial
      protein-protein interactions in the cell but is also an attractive scaffold in
      synthetic biology and material science and a potential target for disease
      intervention. Therefore a systematic understanding of the coiled-coil
      interactions (CCIs) at the organismal level would help unravel the full spectrum
      of the biological function of this interaction motif and facilitate its
      application in therapeutics. We report the first identified genome-wide CCI
      network in Saccharomyces cerevisiae, which consists of 3495 pair-wise
      interactions among 598 predicted coiled-coil regions. Computational analysis
      revealed that the CCI network is specifically and functionally organized and
      extensively involved in the organization of cell machinery. We further show that
      CCIs play a critical role in the assembly of the kinetochore, and disruption of
      the CCI network leads to defects in kinetochore assembly and cell division. The
      CCI network identified in this study is a valuable resource for systematic
      characterization of coiled coils in the shaping and regulation of a host of
      cellular machineries and provides a basis for the utilization of coiled coils as
      domain-based probes for network perturbation and pharmacological applications.

PMID- 22875990
TI  - Delineation of glutamate pathways and secretory responses in pancreatic islets
      with beta-cell-specific abrogation of the glutamate dehydrogenase.
AB  - In pancreatic beta-cells, glutamate dehydrogenase (GDH) modulates insulin
      secretion, although its function regarding specific secretagogues is unclear.
      This study investigated the role of GDH using a beta-cell-specific GDH knockout
      mouse model, called betaGlud1(-/-). The absence of GDH in islets isolated from
      betaGlud1(-/-) mice resulted in abrogation of insulin release evoked by glutamine
      combined with 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid or l-leucine.
      Reintroduction of GDH in betaGlud1(-/-) islets fully restored the secretory
      response. Regarding glucose stimulation, insulin secretion in islets isolated
      from betaGlud1(-/-) mice exhibited half of the response measured in control
      islets. The amplifying pathway, tested at stimulatory glucose concentrations in
      the presence of KCl and diazoxide, was markedly inhibited in betaGlud1(-/-)
      islets. On glucose stimulation, net synthesis of glutamate from alpha
      ketoglutarate was impaired in GDH-deficient islets. Accordingly, glucose-induced
      elevation of glutamate levels observed in control islets was absent in betaGlud1(
      /-) islets. Parallel biochemical pathways, namely alanine and aspartate
      aminotransferases, could not compensate for the lack of GDH. However, the
      secretory response to glucose was fully restored by the provision of cellular
      glutamate when betaGlud1(-/-) islets were exposed to dimethyl glutamate. This
      shows that permissive levels of glutamate are required for the full development
      of glucose-stimulated insulin secretion and that GDH plays an indispensable role
      in this process.

PMID- 22875989
TI  - PTEN, a widely known negative regulator of insulin/PI3K signaling, positively
      regulates neuronal insulin resistance.
AB  - Lipid and protein tyrosine phosphatase, phosphatase and tension homologue (PTEN),
      is a widely known negative regulator of insulin/phosphoinositide 3-kinase
      signaling. Down-regulation of PTEN is thus widely documented to ameliorate
      insulin resistance in peripheral tissues such as skeletal muscle and adipose.
      However, not much is known about its exact role in neuronal insulin signaling and
      insulin resistance. Moreover, alterations of PTEN in neuronal systems have led to
      discovery of several unexpected outcomes, including in the neurodegenerative
      disorder Alzheimer's disease (AD), which is increasingly being recognized as a
      brain-specific form of diabetes. In addition, contrary to expectations, its
      neuron-specific deletion in mice resulted in development of diet-sensitive
      obesity. The present study shows that PTEN, paradoxically, positively regulates
      neuronal insulin signaling and glucose uptake. Its down-regulation exacerbates
      neuronal insulin resistance. The positive role of PTEN in neuronal insulin
      signaling is likely due to its protein phosphatase actions, which prevents the
      activation of focal adhesion kinase (FAK) and extracellular signal-regulated
      kinase (ERK), the kinases critically involved in neuronal energy impairment and
      neurodegeneration. Results suggest that PTEN acting through FAK, the direct
      protein substrate of PTEN, prevents ERK activation. Our findings provide an
      explanation for unexpected outcomes reported earlier with PTEN alterations in
      neuronal systems and also suggest a novel molecular pathway linking neuronal
      insulin resistance and AD, the two pathophysiological states demonstrated to be
      closely linked.

PMID- 22875991
TI  - Translation suppression promotes stress granule formation and cell survival in
      response to cold shock.
AB  - Cells respond to different types of stress by inhibition of protein synthesis and
      subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain
      stalled translation preinitiation complexes. Global translation is regulated
      through the translation initiation factor eukaryotic initiation factor 2alpha
      (eIF2alpha) and the mTOR pathway. Here we identify cold shock as a novel trigger
      of SG assembly in yeast and mammals. Whereas cold shock-induced SGs take hours to
      form, they dissolve within minutes when cells are returned to optimal growth
      temperatures. Cold shock causes eIF2alpha phosphorylation through the kinase PERK
      in mammalian cells, yet this pathway is not alone responsible for translation
      arrest and SG formation. In addition, cold shock leads to reduced mitochondrial
      function, energy depletion, concomitant activation of AMP-activated protein
      kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological
      inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular
      survival in a translation-dependent manner. Our results demonstrate that cells
      actively suppress protein synthesis by parallel pathways, which induce SG
      formation and ensure cellular survival during hypothermia.

PMID- 22875992
TI  - Physical association of the WC-1 photoreceptor and the histone acetyltransferase
      NGF-1 is required for blue light signal transduction in Neurospora crassa.
AB  - In Neurospora crassa and other filamentous fungi, light-dependent-specific
      phenomena are regulated by transcription factors WC-1 and WC-2. In addition to
      its transcriptional activity, WC-1 is able to directly sense light stimuli
      through a LOV sensor domain. Its location in the nucleus and heterodimerization
      with WC-2, together with the presence of a zinc-finger DNA-binding domain and an
      environmental sensor domain, all resemble the functional evolutionary
      architecture adopted by vertebrate nuclear receptors (NRs). Here we describe a
      scenario in which WC-1 represents a functional orthologue of NRs and acts through
      association with the chromatin-modifying coactivator NGF-1, which encodes a
      homologue of the yeast Gcn5p acetyltransferase. To support this view, we show a
      direct association between WC-1 and NGF-1 that depends on a WC-1 region
      containing a conserved functional LXXLL motif, a signature previously described
      as being an exclusive feature of NR/coactivator interaction. Our data suggest
      that a WC-1/NGF-1 complex is preassembled in the dark on light-inducible
      promoters and that, after exposure to light stimulation, NGF-1-associated HAT
      activity leads to histone H3 acetylation and transcriptional activation. Finally,
      we provide evidence for a NGF-1-independent acetylated form of WC-1. Overall our
      data indicate that Neurospora and higher eukaryotes share a common mechanism for
      the signal transduction of environmental stimuli.

PMID- 22875993
TI  - Alternative splicing results in RET isoforms with distinct trafficking
      properties.
AB  - RET encodes a receptor tyrosine kinase that is essential for spermatogenesis,
      development of the sensory, sympathetic, parasympathetic, and enteric nervous
      systems and the kidneys, as well as for maintenance of adult midbrain
      dopaminergic neurons. RET is alternatively spliced to encode multiple isoforms
      that differ in their C-terminal amino acids. The RET9 and RET51 isoforms display
      unique levels of autophosphorylation and have differential interactions with
      adaptor proteins. They induce distinct gene expression patterns, promote
      different levels of cell differentiation and transformation, and play unique
      roles in development. Here we present a comprehensive study of the subcellular
      localization and trafficking of RET isoforms. We show that immature RET9
      accumulates intracellularly in the Golgi, whereas RET51 is efficiently matured
      and present in relatively higher amounts on the plasma membrane. RET51 is
      internalized faster after ligand binding and undergoes recycling back to the
      plasma membrane. This differential trafficking of RET isoforms produces a more
      rapid and longer duration of signaling through the extracellular-signal regulated
      kinase/mitogen-activated protein kinase pathway downstream of RET51 relative to
      RET9. Together these differences in trafficking properties contribute to some of
      the functional differences previously observed between RET9 and RET51 and
      establish the important role of intracellular trafficking in modulating and
      maintaining RET signaling.

PMID- 22875995
TI  - Synthesis, catalytic activity, and leaching studies of a heterogeneous Pd
      catalyst including an immobilized bis(oxazoline) ligand.
AB  - The synthesis and characterization of a novel catalytic system including
      Pd(OAc)(2) attached to a bis(oxazoline) (=BOX) ligand that is covalently bonded
      to 3-mercaptopropyl-functionalized silica gel is presented. The catalyst was
      tested for Suzuki-Miyaura reactions of different aryl halides with phenylboronic
      acid. The heterogeneity of the catalytic system was investigated using different
      approaches, indicating that there is virtually no Pd leaching into the reaction
      solution under the applied reaction conditions. Furthermore, our results show
      that the catalytic system can be reused multiple times without significant loss
      of stability or structure.

PMID- 22875996
TI  - In situ XPS study of methanol reforming on PdGa near-surface intermetallic
      phases.
AB  - In situ X-ray photoelectron spectroscopy and low-energy ion scattering were used
      to study the preparation, (thermo)chemical and catalytic properties of 1:1 PdGa
      intermetallic near-surface phases. Deposition of several multilayers of Ga metal
      and subsequent annealing to 503-523 K led to the formation of a multi-layered 1:1
      PdGa near-surface state without desorption of excess Ga to the gas phase. In
      general, the composition of the PdGa model system is much more variable than that
      of its PdZn counterpart, which results in gradual changes of the near-surface
      composition with increasing annealing or reaction temperature.In contrast to near
      surface PdZn, in methanol steam reforming, no temperature region with pronounced
      CO(2) selectivity was observed, which is due to the inability of purely
      intermetallic PdGa to efficiently activate water. This allows to pinpoint the
      water-activating role of the intermetallic/support interface and/or of the oxide
      support in the related supported Pd(x)Ga/Ga(2)O(3) systems, which exhibit high
      CO(2) selectivity in a broad temperature range. In contrast, corresponding
      experiments starting on the purely bimetallic model surface in oxidative methanol
      reforming yielded high CO(2) selectivity already at low temperatures (~460 K),
      which is due to efficient O(2) activation on PdGa. In situ detected partial and
      reversible oxidative Ga segregation on intermetallic PdGa is associated with
      total oxidation of intermediate C(1) oxygenates to CO(2).

PMID- 22875994
TI  - Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse
      mammary epithelial cells.
AB  - Epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression
      and metastasis, requiring cooperation of the epidermal growth factor/Ras with the
      transforming growth factor-beta (TGF-beta) signaling pathway in a multistep
      process. The molecular mechanisms by which Ras signaling contributes to EMT,
      however, remain elusive to a large extent. We therefore examined the
      transcriptional repressor Ets2-repressor factor (ERF)-a bona fide Ras
      extracellular signal-regulated kinase/mitogen-activated protein kinase effector
      for its ability to interfere with TGF-beta-induced EMT in mammary epithelial
      cells (EpH4) expressing oncogenic Ras (EpRas). ERF-overexpressing EpRas cells
      failed to undergo TGF-beta-induced EMT, formed three-dimensional tubular
      structures in collagen gels, and retained expression of epithelial markers.
      Transcriptome analysis indicated that TGF-beta signaling through Smads was mostly
      unaffected, and ERF suppressed the TGF-beta-induced EMT via Semaphorin-7a
      repression. Forced expression of Semaphorin-7a in ERF-overexpressing EpRas cells
      reestablished their ability to undergo EMT. In contrast, inhibition of Semaphorin
      7a in the parental EpRas cells inhibited their ability to undergo TGF-beta
      induced EMT. Our data suggest that oncogenic Ras may play an additional role in
      EMT via the ERF, regulating Semaphorin-7a and providing a new interconnection
      between the Ras- and the TGF-beta-signaling pathways.

PMID- 22875997
TI  - Career Guidance and Counseling for University Students in China.
AB  - In recent years, various forms of career guidance and career counseling have
      become more prominent and better serviced in most universities throughout the
      world. Such services are obviously to the benefit of the students themselves and
      for society. After an initially slow start, researchers and practitioners in
      China have now begun to focus on the localization of guidance and counselling
      theory and strategies in order to match more exactly actual employment situations
      in different regions of the country. This should result in a service that meets
      students' needs more effectively. Using mainly core literature examining the
      context of career guidance and counseling in China from 2001 to the present, this
      paper elaborates on the current situation and summarizes the progress that has
      been made. The authors detail the content, implementation, problems that exist,
      and ways of improving projects of this kind in Chinese universities. Conclusions
      and suggestions for further research on career guidance and counseling are
      provided.

PMID- 22875998
TI  - Sense of Place and Health in Hamilton, Ontario: A Case Study.
AB  - The concept of sense of place has received considerable attention by social
      scientists in recent years. Research has indicated that a person's sense of place
      is influenced by a number of factors including the built environment, socio
      economic status (SES), well-being and health. Relatively few studies have
      examined sense of place at the neighbourhood level, particularly among
      communities exhibiting different levels of SES. This article investigates sense
      of place among three neighbourhood groups in Hamilton, Ontario representing areas
      of low, mixed and high SES. It analyses data from a 16-point sense of place scale
      derived from the Hamilton Household Quality of Life Survey carried out in 2010
      2011 among 1,002 respondents. The paper found that sense of place was highest
      among residents of the high SES neighbourhood group as well as among home owners,
      people residing in single-detached homes, retired residents and those living in
      their neighbourhood for more than 10 years. From a health perspective, the paper
      found that a strong association existed between sense of place and self-perceived
      mental health across the three neighbourhood groups. Furthermore, by way of
      regression modeling, the paper examined the factors influencing health-related
      sense of place. Among the sample of respondents, a strong connection was found
      between housing, particularly home ownership, and high levels of health-related
      sense of place.

PMID- 22875999
TI  - Socio-Cultural Dispositions and Wellbeing of the Women Left Behind: A Case of
      Migrant Households in Nepal.
AB  - The concept of wellbeing is gaining popularity in the study of quality of life
      and cultural significance of living. The paper aims to contribute to our
      understanding of objective and subjective wellbeing by exploring the perceptions
      of women left behind by out-migrating husbands on their quality of life in a
      transnational social field. The paper uses both qualitative and quantitative
      research methods. Its primary focus is on the life stories of the four women left
      behind by their migrant husbands, complementing by quantitative data obtained
      from a survey among 277 households. Taking an example from Nepal's eastern terai,
      the paper shows that additional income from remittances has increased the
      objective wellbeing of the women left behind, but it may not have increased their
      subjective wellbeing. Hence, it is concluded that improved objective wellbeing of
      a woman does not necessarily translate into her (improved) subjective wellbeing.
      The subjective experiences are rather complex, multi-faceted and context specific
      depending on the family situation, socio-cultural disposition and prior economic
      situation of the actors involved.

PMID- 22876000
TI  - Measurements of the strong-interaction widths of the kaonic (3)He and (4)He 2p
      levels.
AB  - The kaonic (3)He and (4)He X-rays emitted in the [Formula: see text] transitions
      were measured in the SIDDHARTA experiment. The widths of the kaonic (3)He and
      (4)He 2p states were determined to be [Formula: see text], and [Formula: see
      text], respectively. Both results are consistent with the theoretical
      predictions. The width of kaonic (4)He is much smaller than the value of
      [Formula: see text] determined by the experiments performed in the 70's and 80's,
      while the width of kaonic (3)He was determined for the first time.

PMID- 22876001
TI  - Enriching our archives....

PMID- 22876002
TI  - Endodontics - Current and future.

PMID- 22876003
TI  - Research methodology in dentistry: Part II - The relevance of statistics in
      research.
AB  - The lifeline of original research depends on adept statistical analysis. However,
      there have been reports of statistical misconduct in studies that could arise
      from the inadequate understanding of the fundamental of statistics. There have
      been several reports on this across medical and dental literature. This article
      aims at encouraging the reader to approach statistics from its logic rather than
      its theoretical perspective. The article also provides information on statistical
      misuse in the Journal of Conservative Dentistry between the years 2008 and 2011.

PMID- 22876004
TI  - Effect of five commercial mouth rinses on the microhardness of a nanofilled resin
      composite restorative material: An in vitro study.
AB  - AIM AND OBJECTIVES: This in vitro study was designed to comparatively evaluate
      the effect of five commercial mouth rinses on the micro hardness of a nanofilled
      resin based restorative material. MATERIALS AND METHODS: Fifty specimens of resin
      composite material (Filtek Z350XT, 3M ESPE, St.Paul, MN USA) were prepared and
      immersed in artificial saliva for 24 h. The base line micro hardness of specimens
      was recorded using Vicker's micro hardness tester (MMT - X7 Matsuzawa, Japan).
      The specimens were randomly distributed into five groups, each containing 10
      specimens (n=10) as follows - Group I Listerine (alcohol based), Group II
      Periogard (alcohol based), Group III Colgate plax (alcohol based), Group IV C-
      prev (alcohol free), Group V Hiora(alcohol free). The specimens were immersed in
      20 ml of mouth rinses and incubated for 24 h at 37 degrees C. The post immersion
      micro hardness values of the specimens were recorded and the data was tabulated
      for statistical analysis. Kruskal-Wallis test was used for inter group comparison
      followed by pair wise comparison of groups using Mann-Whitney U test. The level
      of significance was set at P=0.05. RESULTS: Significant reduction in the mean VHN
      (Vicker's micro hardness number) was observed in all the groups after exposure to
      the tested mouth rinses (P<0.01) and the reduction in mean VHN values were as
      follows: Group I 12.09, Group II 3.42, Group II 1.51, Group IV 1.03, Group V
      0.57. Inter group comparison showed statistically significant reduction in micro
      hardness in Groups I and II compared to all other groups with P<0.001. There was
      no significant difference between Groups III, IV and V. CONCLUSION: All the mouth
      rinses showed a reduction in the microhardness of nanofilled resin composite
      material with listerine (Group I) containing maximum amount of alcohol, showing
      highest reduction in micro hardness value.

PMID- 22876005
TI  - Detection of residual obturation material after root canal retreatment with three
      different techniques using a dental operating microscope and a stereomicroscope:
      An in vitro comparative evaluation.
AB  - AIM: The study was designed to compare the efficiency of three different methods
      used for retreatment using a dental operating microscope (DOM) and a
      stereomicroscope and to evaluate and compare the two methods for detection of
      residual obturation material after retreatment. BACKGROUND: The DOM can play an
      important role in the successful retreatment by detecting the remaining
      obturation material. MATERIALS AND METHODS: Thirty extracted maxillary central
      incisors were collected and obturated after biomechanical preparation. The
      samples were divided into three groups depending on the method of retreatment:
      Group I, H-files; Group II, ProTaper Universal retreatment files; and Group III:
      H-files + Gates-Glidden drills, with 10 samples in each group. After retreatment,
      the samples were observed under a DOM for detection of residual obturation
      material. Later, the teeth were cleared and observed under a stereomicroscope for
      detecting the remaining filling material. The results were subjected to the
      Spearman's rank order test and other statistical analysis. RESULTS: The maximum
      cleanliness of the root canal walls was seen in Group I while Group II showed the
      least. The difference between the mean scores obtained with a DOM and a
      stereomicroscope was statistically significant (P = 0.05). CONCLUSION: None of
      the techniques could completely remove the obturation material. The root canal
      cleanliness is best achieved when retreatment is performed under a DOM.

PMID- 22876006
TI  - An in vitro evaluation of fracture strength of endodontically treated teeth with
      simulated flared root canals restored with different post and core systems.
AB  - PURPOSE: The objective of this study is to evaluate the fracture strength and
      mode of failure of endodontically treated teeth with flared canals restored with
      two fiber reinforced systems (glass fiber and quartz fiber) and one base metal
      cast post and core system. MATERIALS AND METHODS: Forty five anterior teeth were
      decoronated at cemento-enamel junction and were endodontically treated. Post
      space was prepared and randomly divided into three groups according to post
      system. Specimens were loaded at 45 degrees  in a universal testing machine at a
      cross head speed of 0.5 mm/min until failure. The mode of failure was classified
      as repairable or non-repairable. RESULTS: Teeth restored with cast posts have
      fracture strength twice that of teeth restored with fiber posts. Fiber-reinforced
      posts failed at a certain compressive force but they were repairable unlike the
      non-repairable fracture seen with cast posts. CONCLUSION: The results of this
      study showed that, fracture strength and mode of failure in anterior teeth with
      flared canals varied according to the type of post used to support a crown.

PMID- 22876007
TI  - Effect of surface treatment on micro shear bond strength of two indirect
      composites.
AB  - AIM: To determine the effect of surface treatment on micro shear bond strength of
      two indirect composites. MATERIALS AND METHODS: Blocks of 2 * 7 * 20 mm
      dimensions were made from two kinds of resin composites, Gradia and Signum plus.
      Samples were subjected to secondary curing to complete polymerization. They were
      divided into five groups: control without any preparation, second group
      sandblasted with aluminum oxide, third, fourth and fifth groups were lased under
      a beam of 0.5, 1 and 2 W respectively. Panavia resin cement was placed on the
      composite blocks using tygon tubes and cured and micro shear bond strength was
      measured. One sample of each group was observed under electronic microscope. Data
      was analyzed by two-way ANOVA and Tukey's multiple comparison tests. RESULTS: For
      Gradia composite, the sandblasted group showed highest strength (25.7+/-2.9 MPa)
      followed by the laser beam of 1 W group (with 23.6+/- 2.8 MPa). In Signum
      composite, the laser beam of 1 W (21.4+/-4.2 MPa) showed the highest strength
      followed by the sandblasted group (with 19.4+/-3.2 MPa). CONCLUSION: Surface
      treatments using sandblast and laser beam of 1W power along with silane are two
      effective methods to increase the bond strength of composites.

PMID- 22876008
TI  - Comparative evaluation of traditional and self-priming hydrophilic resin.
AB  - BACKGROUND: The purpose of this study was to compare the microleakage of
      traditional composite (Charisma/Gluma Comfort Bond) and self-priming resin
      (Embrace Wetbond). MATERIALS AND METHODS: Standardized Class V cavities partly in
      enamel and cementum were prepared in 20 extracted human premolars. Teeth were
      divided into two groups. Group 1 was restored with Charisma/Gluma Comfort Bond
      and Group 2 with Embrace Wetbond. The specimens were stored in distilled water at
      room temperature for 24 h and then subjected to 200 thermocycles at 5 degrees C
      and 55 degrees C with a 1 min dwell time. After thermocycling teeth were immersed
      in a 0.2% solution of methylene blue dye for 24 h. Teeth were sectioned
      vertically approximately midway through the facial and lingual surfaces using a
      diamond saw blade. Microleakage was evaluated at enamel and cementum surfaces
      using 10 * stereomicroscope. The statistical analysis was performed using
      Wilcoxon signed-rank test. RESULTS: Wetbond showed less microleakage at occlusal
      and gingival margins as compared with Charisma/Gluma Comfort Bond and the results
      were statistically significant (P < 0.05). CONCLUSION: Class V cavities restored
      with Embrace Wetbond with fewer steps and fewer materials offers greater
      protection against microleakage at the tooth restorative interface.

PMID- 22876009
TI  - Evaluation of Vickers hardness and depth of cure of six composite resins photo
      activated with different polymerization modes.
AB  - AIM: The current in vitro study evaluated Vickers hardness (VK) and depth of cure
      (hardness ratio) of six resin composites, polymerized with a light-emitting diode
      (LED) curing unit by different polymerization modes: Standard 20 s, Standard 40
      s, Soft-start 40 s. MATERIALS AND METHODS: SIX RESIN COMPOSITES WERE SELECTED FOR
      THE PRESENT STUDY: three microhybrid (Esthet.X HD, Amaris, Filtek Silorane), two
      nanohybrid (Grandio, Ceram.X mono) and one nanofilled (Filtek Supreme XT). The VK
      of the surface was determined with a microhardness tester using a Vickers diamond
      indenter and a 200 g load applied for 15 seconds. The mean VK and hardness ratio
      of the specimens were calculated using the formula: hardness ratio = VK of bottom
      surface / VK of top surface. RESULTS: For all the materials tested and with all
      the polymerization modes, hardness ratio was higher than the minimum value
      indicated in literature in order to consider the bottom surface as adequately
      cured (0.80). Curing time did not affect hardness ratio values for Filtek
      Silorane, Grandio and Filtek Supreme XT. CONCLUSION: The effectiveness of cure at
      the top and bottom surface was not affected by Soft-start polymerization mode.

PMID- 22876010
TI  - Micro-tensile bond strength of adhesives to pulp chamber dentin after irrigation
      with Ethylenediaminetetraacetic acid.
AB  - AIM: The aim of this study was to evaluate the influence of different
      concentrations of Ethylenediaminetetraacetic acid (EDTA) solution on adhesion,
      that is, the bond strength of the different adhesive systems, to the pulp chamber
      dentin. MATERIALS AND METHODS: Recently extracted, sound, human, third molars
      were cut horizontally to expose the pulp horn. The roof of the pulp chamber and
      pulp tissue was removed. The teeth were then divided into five main groups. The
      teeth in each group were treated as follows: group 1, irrigated with saline;
      group 2, with 5% EDTA for 5 minutes; group 3, with 15% EDTA for 5 minutes; group
      4, with 17% EDTA for 5 minutes and group 5, with 19% EDTA for 5 minutes. Treated
      specimens were dried and divided into 2 subgroups for adhesives; bonded with a
      total-etching adhesive (Adper Scotchbond Multi-purpose - ASB) or a one bottle of
      self-etch adhesive system (Clearfil S3 Bond - CS3). After the bonding procedure
      and composite restoration, teeth were sectioned and dentin sticks were obtained
      from each group for micro tensile testing (n = 10). Micro tensile testing was
      performed and scanning electron microscope (SEM) photographs were taken for each
      irrigated group. RESULTS: In the ASB group, saline showed statistically higher
      bond strength values at the different concentrations of EDTA, while the micro
      tensile bond strengths of the different concentrations of EDTA were not
      statistically different. In the CS3 group, saline and 5% EDTA showed
      statistically higher bond strength values than 17% and 19% EDTA, while the micro
      tensile bond strengths of 15% EDTA compared to saline and 5% EDTA and 15% EDTA
      compared to 17% EDTA and 19% EDTA, were not statistically different. CONCLUSION:
      This study showed that EDTA irrigation can affect the bond strength of adhesive
      systems on pulp chamber lateral walls. Clinically, low EDTA concentrations can be
      recommended if self-etch adhesives have been selected.

PMID- 22876011
TI  - Evaluation of antimicrobial efficacy of Aloe vera and its effectiveness in
      decontaminating gutta percha cones.
AB  - AIM: The aim of this study was to evaluate the antimicrobial efficacy of Aloe
      vera and to determine its effectiveness in decontaminating gutta percha cones.
      MATERIALS AND METHODS: A concentrated extract of Aloe vera was used to check for
      the antimicrobial efficacy using the agar well diffusion method. Presence of
      zones' of diffusion was identified against three common GP contaminants namely,
      E.coli, E.faecalis and Staph. aureus. New GP Cones, freshly taken out of the
      packet were then decontaminated for 1minute using Aloe vera gel and then placed
      in thioglycolate broth to check for the presence of turbidity. RESULTS: The zones
      of inhibition on the agar plate were measured as 24mm,21mm and 24mm respectively.
      The broth remained clear even after 48 hours of incubation. CONCLUSION: We
      conclude that Aloe vera is indeed effective as a GP decontaminant and it holds a
      promising future as a medium for storage of GP cones.

PMID- 22876012
TI  - In vitro comparative study of sealing ability of Diadent BioAggregate and other
      root-end filling materials.
AB  - AIM: This in vitro study evaluated and compared sealing ability of Diadent
      BioAggregate (DBA) as a new root-end filling material (REFM) versus amalgam,
      intermediate restorative material (IRM) and white mineral trioxide aggregate
      (WMTA). MATERIALS AND METHODS: Crowns of sixty extracted human maxillary incisors
      were sectioned at the cemento-enamel junction (CEJ). All the roots were
      instrumented and obturated with gutta-percha and resin sealer. Obturated roots
      were divided randomly into 2 control groups and 4 experimental groups of 10
      samples each. In the negative control group (group I), roots were kept without
      any further preparation. In the positive and experimental groups roots, were
      apically resected and root-end cavities were prepared and filled with: (a) gutta
      percha (group 2-positive control group); (b) amalgam (group 3); (c) IRM (group
      4); (d) WMTA (group 5); (e) DBA (group 6). Apical leakage was assessed using dye
      penetration technique. Data were submitted to statistical analysis by the one-way
      analysis of variance (ANOVA) and Tukey's test. RESULTS: Significant difference of
      sealing ability was found among 4 tested groups. DBA followed by MTA showed the
      highest sealing ability. CONCLUSIONS: DBA with its high sealing ability can be
      considered a possible alternative to MTA.

PMID- 22876013
TI  - A self-designed instrument to evaluate cavosurface angle for class I amalgam
      cavity preparation: A learning aid.
AB  - Fighting the controversies, amalgam, as a posterior restorative material has
      survived till date. The fate of amalgam restoration is determined by geometry of
      the cavity preparation and cavosurface angle is one integral part of the cavity,
      which decides the marginal characteristics of the restoration and health of the
      tooth. Low edge strength of amalgam highlights the importance of cavosurface
      angle. However, at the same time conservation of the tooth also should be
      considered. This article presents a self-designed instrument to evaluate and
      obtain a cavosurface angle close to 110 degrees . The design of the instrument
      also helps in evaluating parameters, such as depth of the cavity, undercut angle,
      and allows finishing of the buccal or lingual walls.

PMID- 22876014
TI  - The effect of different sealer placement techniques on sealing Ability: An in
      vitro study.
AB  - AIM: The aim of this in vitro study was to evaluate the sealing ability of an
      endodontic sealer following different techniques of its placement. MATERIALS AND
      METHODS: A total of 119 permanent human anterior teeth were prepared by using
      manual Protaper((r)) and randomly divided into three equal groups of 33 teeth
      each. The teeth were obturated with the cold lateral condensation technique and
      AH26 sealer which was placed by using the following: G1: rotary lentulo spiral;
      G2: manual lentulo spiral; and G3: master gutta-percha coating. The remaining 20
      teeth served as positive and negative controls. The samples were immersed in the
      methylene blue solution for 3 days and longitudinally sectioned for dye
      penetration assessment and analyzed using a stereomicroscope. RESULTS: There was
      no statistically significant difference (P = 0.305) among the three groups.
      However, the rotary lentulo spiral technique and the master gutta-percha coating
      technique showed the highest (4.5 mm) and the lowest (3.8 mm) microleakage
      values, respectively. CONCLUSION: Different techniques of sealer placement used
      in this study provided a comparable seal. However, the master gutta-percha
      coating technique might be preferable because of its ease of use.

PMID- 22876015
TI  - An in vitro comparison of penetration depth of two root canal sealers: An SEM
      study.
AB  - AIM: The aim of this study was to examine in vitro penetration depth of two resin
      based sealers (AH plus and Resino Seal) and Zinc Oxide Eugenol sealer into the
      dentinal tubules after removing smear layer by passive ultrasonic irrigation.
      MATERIALS AND METHODS: Thirty freshly extracted maxillary central incisors were
      used. The teeth were decoronated, working length established and prepared upto
      size 40 file. Each root was subjected to passive ultrasonic irrigation with 2.5%
      sodium hypochlorite. Three different sealers and gutta-percha were used for
      obturation. Roots were sectioned using hard tissue microtome. These sections were
      gold sputtered and examined under scanning electron microscope. RESULTS:
      Statistical analyses of the data were performed using Kruskal-Wallis and Mann
      Whitney tests. Statistically significant difference was found between AH Plus
      sealer and Resino Seal sealer and Zinc Oxide Eugenol sealer. CONCLUSION: The
      results showed that AH Plus had maximum penetration depth into dentinal tubules.

PMID- 22876016
TI  - The effect of various surface contaminants on the microleakage of two different
      generation bonding agents: A stereomicroscopic study.
AB  - AIM: The aim of this in vitro study was to evaluate the microleakage of two
      different generation bonding agents in the presence of various surface
      contaminants. MATERIALS AND METHODS: Class V cavities were prepared on 150
      extracted human permanent molars. The samples were randomly divided into two main
      groups of 75 teeth each. Group I: Fifth generation bonding system (Single Bond,
      3M). Group II: Seventh generation bonding system (iBond, Kulzer). Subgroups were
      formed according to exposure to different surface contaminants (saliva, blood,
      caries disclosing agent and haemostatic agent). Cavities were restored with
      hybrid composite (Z-100, 3M) and evaluated for microleakage. The scores were
      subjected to 't' test and analysis of variance (ANOVA) test. RESULTS: Single Bond
      and iBond did not provide complete resistance to microleakage when there was no
      contamination. Microleakage was minimum in the no contamination subgroup and
      maximum with the haemostatic agent subgroup for both the groups. CONCLUSION:
      Single bond showed lesser micro leakage in contaminated conditions.

PMID- 22876017
TI  - Effect of saliva and blood contamination on the bond strength of self-etching
      adhesive system- An in vitro study.
AB  - AIM: The aims of this study were to determine the effect of saliva and blood
      contamination on the shear bond strength of self-etching adhesive to enamel and
      dentin; and, to compare the difference in bond strength due to contamination
      beforeand after application of the self-etch adhesive. MATERIALS AND METHODS: 40
      human mandibular molars were wet ground on both buccal and lingual surfaces to
      prepare flat superficial enamel and dentin surfaces. They were randomly divided
      into two groups (n = 40) based on the substrate (enamel and dentin). Each group
      was further divided into five subgroups (n = 8) based on the type of
      contamination it was subjected to, and the step in the bonding sequence when the
      contamination occurred (before or after adhesive application). Fresh saliva and
      fresh human blood were applied either before or after the application of Xeno
      III((r)) self-etching adhesive system (SES). Composite resin was applied as
      inverted, truncated cured cones that were subjected to shear bond strength test.
      STATISTICAL ANALYSIS: One-way analysis of variance (ANOVA) and Tukey's Honestly
      Significant Difference (HSD) test were used. RESULTS: Statistically significant
      reduction in the bond strength was shown after both saliva and blood
      contamination before and after Xeno III((r)) application (P< 0.05). Bond strength
      is significantly reduced after contamination with blood as compared to saliva.
      CONCLUSIONS: When self-etching adhesive systems are used, saliva and blood
      contamination significantly decrease the bond strength of the adhesive to enamel
      and dentin of the tooth.

PMID- 22876018
TI  - Evaluation of the sealing ability of resin cement used as a root canal sealer: An
      in vitro study.
AB  - AIM: This study was designed to evaluate the apical seal of root canals obturated
      with resin cement as a root canal sealer and compare with that of the glass
      ionomer and zinc oxide eugenol sealers using a cold lateral condensation gutta
      percha technique. BACKGROUND: Successful root canal treatment requires three
      dimensional obturation of the root canal system with nonirritating biomaterials.
      None of the available materials are capable of providing a fluid tight seal.
      MATERIALS AND METHODS: The prepared teeth were randomly divided into three groups
      of 15 each to be obturated using three different sealers. Group I: zinc oxide
      eugenol (Tubliseal), Group II: Glass ionomer (Ketac Endo), and Group III: resin
      cement (C & B Superbond). All the specimens were stored in 100% relative humidity
      at 37 degrees  for 24 h. The specimens were placed in 2% methylene blue dye for
      48 h and sectioned. The dye penetration was evaluated under a stereomicroscope.
      RESULTS: The "Kruskal" Wallis test was carried out to test the equality of mean.
      All the specimens showed dye leakage, and there was a statistically significant
      difference (P < 0.0001) among the groups. The specimens in Group III showed a
      minimal leakage and the specimens in Group I showed a maximum leakage.
      CONCLUSION: Resin cement sealed the root canals significantly better when
      compared with zinc oxide eugenol and glass ionomer sealers.

PMID- 22876019
TI  - An in vitro evaluation of shear bond strength of silorane and bis-GMA resin-based
      composite using different curing units.
AB  - AIM: To evaluate shear bond strength of silorane and bis-GMA based composite
      resins using self-etch and total-etch adhesive systems, and compare the effect of
      Quartz-tungten-halogen (QTH) and Light emitting diode (LED) on the shear bond
      strength of the experimental materials. MATERIALS AND METHODS: Flat dentin
      surfaces were exposed on intact extracted molars and composite resin was built 2
      mm in diameter. Teeth were divided randomly into four groups. Groups 1 and 2 were
      restored with P90 system adhesive and Filtek P90 and cured with QTH and LED units
      respectively. Groups 3 and 4 were restored with total etch adhesive and Filtek
      Z100 and cured with QTH and LED units respectively. Specimens were subjected to
      shear bond strength testing using Instrom Universal testing machine. RESULTS:
      Data was subjected to one-way analysis of variance. Total-etch groups gave
      significantly higher shear bond strength values than the self-etch groups. No
      significant difference in shear bond strength was found between Groups 3 and 4,
      while Group 1 showed significantly higher values than Group 2. CONCLUSION: Type
      of light curing unit is not a significant factor affecting shear bond strength
      for bis-GMA RBCs using total-etch technique; while for curing silorane resin
      based composite (RBCs), conventional halogen curing units showed better results.

PMID- 22876020
TI  - Effect of alcoholic and non-alcoholic beverages on color stability and surface
      roughness of resin composites: An in vitro study.
AB  - BACKGROUND: Consumption of certain beverages may affect the esthetic and physical
      properties of the resin composite, thereby undermining the quality of
      restorations. AIM: To analyze the effect of three beverages (Whiskey, Coca-Cola,
      and Nimbooz) on color stability and surface roughness of two different types of
      resin composites at various time intervals in vitro. MATERIALS AND METHODS: A
      methacrylate-based nanofilled composite and a silorane-based microhybrid
      composite were used. Each material was randomly divided into four equal subgroups
      of 10 samples each according to the beverages used (Whiskey, Coca-Cola, Nimbooz,
      and Distilled water). The samples were immersed in each beverage for 10 minutes
      each day for 56 days. Color change and surface roughness measurements were noted
      at the baseline - the seventh, fourteenth, twenty-eighth, and fifty-sixth day.
      STATISTICAL ANALYSIS USED: RANOVA and Bonferroni tests were used to find the
      difference in color change and surface roughness in the two resin composites when
      immersed in different beverages. The Pearson Correlation test was carried out to
      test if any correlation existed between color change and surface roughness.
      RESULTS: Silorane-based resin composites were more stable in different beverages
      over time. CONCLUSION: The effect of interaction of different resin composites,
      various beverages, and time depended on a multitude of factors.

PMID- 22876021
TI  - Evaluation of effect of three different dental unit waterline antimicrobials on
      the shear bond strength to dentin - An ex vivo study.
AB  - BACKGROUND: In restorative treatment dental unit water is used while irrigating
      the cavity and also in the use of composite restorations to flush away the
      etchant to place bonding agent. These antimicrobials may influence the bond
      strength of the dentine bonding agent to the dentine. AIM AND OBJECTIVE: To
      evaluate the effect of three different dental units waterline antimicrobials on
      the shear bond strength of dentin. MATERIALS AND METHODS: Sixty freshly extracted
      human teeth were taken and the occlusal surfaces were sectioned to obtain a flat
      dentin surface. Then the teeth were randomized into 4 groups depending on the
      antimicrobial used: Group 1(Distilled water), Group 2 (Alpron), Group 3
      (CitriSil), and Group 4 (Chlorhexidine). The dentine surface was prepared for
      bonding and composite resin was placed in two increments of 2 mm each. The
      specimens were stored in distilled water, thermo cycled after 7 days shear test
      was performed by using the universal testing machine. RESULT: No significant
      difference between Group 1 and Group 2 with regard to shear bond strength. There
      was a significant difference in the SBS of Group 1 and Group 3 and Group 4. The
      SBS of group 2 was higher than Group 3 and Group 4 and the difference was
      statistically significant. CONCLUSION: Citrisil and Chlorhexidine groups showed
      affected bond strength whereas Alpron did not vary with bond strength.

PMID- 22876022
TI  - Comparative evaluation of the antimicrobial activity of natural extracts of
      Morinda citrifolia, papain and aloe vera (all in gel formulation), 2%
      chlorhexidine gel and calcium hydroxide, against Enterococcus faecalis: An in
      vitro study.
AB  - AIM: A comparative evaluation of the antimicrobial activity of natural extracts
      of Morinda citrifolia, papain, and aloe vera (all in gel formulations), 2%
      chlorhexidine gel and calcium hydroxide, against Enterococcus faecalis-an in
      vitro study. MATERIALS AND METHODS: The antimicrobial efficacy was assessed in
      vitro using dentin shavings collected at 2 depths of 200 and 400 MUm. The total
      colony forming units at the end of 1, 3, and 5 days were assessed. RESULTS: The
      overall percentage inhibition of bacterial growth (200 and 400 MUm depth) was
      100% with chlorhexidine gel. This was followed by M. citrifolia gel (86.02%),
      which showed better antimicrobial efficacy as compared with aloe vera gel
      (78.9%), papain gel (67.3%), and calcium hydroxide (64.3%). There was no
      statistical difference between data at 200 and 400 MUm depth. CONCLUSION:
      Chlorhexidine gel showed the maximum antimicrobial activity against E. faecalis,
      whereas calcium hydroxide showed the least. Among the natural intracanal
      medicaments, M. citrifolia gel consistently exhibited good inhibition up to the
      5(th) day followed by aloe vera gel and papain gel.

PMID- 22876023
TI  - Root resection under the surgical field employed for extraction of impacted tooth
      and management of external resorption.
AB  - This case report illustrates determination of prognosis and immediate resection
      carried out, before completing the endodontic therapy, during the surgery
      employed for managing a nonperiodontal problem. This case showed external
      pressure resorption in the distobuccal root of maxillary second molar caused by
      the impingement of impacted third molar. Extraction of third molar was decided
      when healing was not seen, despite initiating endodontic therapy in second molar.
      Following elevation of flap and extraction of third molar, the poor prognosis due
      to severe bone loss around the resorbed root was evident. But due to strategic
      value of second molar, it was found beneficial to employ resection. Therefore,
      immediate resection was carried out in the same surgical field before the
      completion of endodontic therapy. This prevented the need for another surgical
      entry with its associated trauma to carry out resection separately later.
      Resection followed by the completion of endodontic therapy and full crown
      assisted in salvaging the remaining functional portion of the tooth and prevented
      the occurrence of distal extension with its potential drawbacks.

PMID- 22876024
TI  - Caries-risk assessment with a chairside optical spectroscopic sensor.

PMID- 22876025
TI  - Authors' reply.

PMID- 22876026
TI  - Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles
      in pathogenesis of metabolic syndrome.
AB  - Although new research technologies are constantly used to look either for genes
      or biomarkers in the prediction of metabolic syndrome (MS), the pathogenesis and
      pathophysiology of this complex disease remains a major challenge. Interestingly,
      Cheng et al recently investigated possible pathways underlying MS by high
      throughput metabolite profiling in two large and well characterized community
      based cohorts. The authors explored by liquid chromatography and mass
      spectrometry the plasma concentrations of 45 distinct metabolites and examined
      their relation to cardiometabolic risk, and observed that metabolic risk factors
      such as obesity, insulin resistance (IR), high blood pressure, and dyslipidemia
      were associated with several metabolites, including branched-chain amino acids,
      other hydrophobic amino acids, tryptophan breakdown products, and nucleotide
      metabolites. In addition, the authors found a significant association of IR
      traits with glutamine, glutamate and the glutamine-to-glutamate ratio. These data
      provide new insight into the pathogenesis of MS-associated phenotypes and
      introduce a crucial role of glutamine-cycling pathway as prominently involved in
      the development of metabolic risk. We consider that the hypothesis about the role
      of abnormal glutamate metabolism in the pathogenesis of the MS is certainly
      challenging and suggests the critical role of the liver in the global metabolic
      modulation as glutamate metabolism is linked with aminotransferase reactions. We
      discuss here the critical role of the "liver metabolism" in the pathogenesis of
      the MS and IR, and postulate that before fatty liver develops, abnormal levels of
      liver enzymes, such as alanine and aspartate aminotransferases might reflect high
      levels of hepatic transamination of amino acids in the liver.

PMID- 22876027
TI  - Diagnostic and therapeutic implications of the association between ferritin level
      and severity of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), defined by excessive liver fat
      deposition related to the metabolic syndrome, is a leading cause of progressive
      liver disease, for which accurate non-invasive staging systems and effective
      treatments are still lacking. Evidence has shown that increased ferritin levels
      are associated with the metabolic insulin resistance syndrome, and higher hepatic
      iron and fat content. Hyperferritinemia and iron stores have been associated with
      the severity of liver damage in NAFLD, and iron depletion reduced insulin
      resistance and liver enzymes. Recently, Kowdley et al demonstrated in a
      multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical
      research network database with central re-evaluation of liver histology and iron
      staining that the increased serum ferritin level is an independent predictor of
      liver damage in patients with NAFLD, and is useful to identify NAFLD patients at
      risk of non-alcoholic steatohepatitis and advanced fibrosis. These data indicate
      that incorporation of serum ferritin level may improve the performance of
      noninvasive scoring of liver damage in patients with NAFLD, and that iron
      depletion still represents an attractive therapeutic target to prevent the
      progression of liver damage in these patients.

PMID- 22876028
TI  - Tight glycemic control using an artificial endocrine pancreas may play an
      important role in preventing infection after pancreatic resection.
AB  - It is well known that perioperative hyperglycemia is the main cause of infectious
      complications after surgery. To improve perioperative glycemic control, we wish
      to highlight and comment on an interesting paper published recently by the Annals
      of Surgery entitled: "Early postoperative hyperglycemia is associated with
      postoperative complications after pancreatoduodenectomy (PD)" by Eshuis et al.
      The authors concluded that early postoperative glucose levels more than 140 mg/dL
      was significantly associated with complications after PD. Since we recommend that
      perioperative tight glycemic control (TGC) is an effective method to prevent
      postoperative complications including surgical site infection after distal,
      proximal, and total pancreatic resection, we support strongly this conclusion
      drawn in this article. However, if early postoperative glucose control in
      patients undergoing PD was administrated by conventional method such as sliding
      scale approach as described in this article, it is difficult to maintain TGC.
      Therefore, we introduce a novel perioperative glycemic control using an
      artificial endocrine pancreas against pancreatogenic diabetes after pancreatic
      resection including PD.

PMID- 22876029
TI  - Crucial steps in the natural history of inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's
      disease (CD), are chronic, progressive and disabling disorders. Over the last few
      decades, new therapeutic approaches have been introduced which have led not only
      to a reduction in the mortality rate but also offered the possibility of a
      favorable modification in the natural history of IBD. The identification of
      clinical, genetic and serological prognostic factors has permitted a better
      stratification of the disease, thus allowing the opportunity to indicate the most
      appropriate therapy. Early treatment with immunosuppressive drugs and biologics
      has offered the opportunity to change, at least in the short term, the course of
      the disease by reducing, in a subset of patients with IBD, hospitalization and
      the need for surgery. In this review, the crucial steps in the natural history of
      both UC and CD will be discussed, as well as the factors that may change their
      clinical course. The methodological requirements for high quality studies on the
      course and prognosis of IBD, the true impact of environmental and dietary factors
      on the clinical course of IBD, the clinical, serological and genetic predictors
      of the IBD course (in particular, which of these are relevant and appropriate for
      use in clinical practice), the impact of the various forms of medical treatment
      on the IBD complication rate, the role of surgery for IBD in the biologic era,
      the true magnitude of risk of colorectal cancer associated with IBD, as well as
      the mortality rate related to IBD will be stressed; all topics that are
      extensively discussed in separate reviews included in this issue of World Journal
      of Gastroenterology.

PMID- 22876030
TI  - Methodology for high-quality studies on course and prognosis of inflammatory
      bowel disease.
AB  - Inflammatory bowel diseases (IBDs) are characterized by a chronic course with an
      alternation of relapses and remissions. Questions about prognosis are important
      for the patient who wants to know how the disease will affect his/her life and
      also for clinicians to make management decisions. Correct selection of the
      patients is the basis for good methodological studies on the course of IBD. A
      great proportion of data on the course of IBD is derived from a limited number of
      cohort studies. Studies help to define the endpoints for clinical trials and to
      identify subsets of patients in whom the prognosis of the disease can be
      stratified according to clinical features. Specific scientific requirements for
      high-quality studies on prognosis are the following: use of inception cohort,
      description of referral patterns, completeness of follow-up, objective outcome
      criteria, blind outcome assessment, adjustment for extraneous prognostic factors
      and statistical issues. We analyzed each of these requirements in studies on
      IBDs. To date, prospective and population-based cohort studies are the standard
      for an unbiased assessment of prognosis. A better knowledge of the course of
      disease of chronic disorders ideally requires: (1) data from population-based
      studies, to avoid selection bias from referral centers in which patients with a
      more severe disease are usually treated; (2) inclusion of patients seen at the
      onset of the disease excluding misdiagnosed cases; and (3) follow-up from the
      onset of the disease to the end without dropouts.

PMID- 22876031
TI  - Clinical, serological and genetic predictors of inflammatory bowel disease
      course.
AB  - Patients with extensive or complicated Crohn's disease (CD) at diagnosis should
      be treated straightaway with immunosuppressive therapy according to the most
      recent guidelines. In patients with localized and uncomplicated CD at diagnosis,
      early use of immunosuppressive therapy is debated for preventing disease
      progression and limiting the disabling clinical impact. In this context, there is
      a need for predictors of benign or unfavourable subsequent clinical course, in
      order to avoid over-treating with risky drugs those patients who would have
      experienced spontaneous mid-term asymptomatic disease without progression towards
      irreversible intestinal lesions. At diagnosis, an age below 40 years, the
      presence of perianal lesions and the need for treating the first flare with
      steroids have been consistently associated with an unfavourable subsequent 5-year
      or 10-year clinical course. The positive predictive value of unfavourable course
      in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population
      based and referral centre cohorts. Consequently, the use of these predictors can
      be integrated into the elements that influence individual decisions. In the CD
      postoperative context, keeping smoking and history of prior resection are the
      strongest predictors of disease symptomatic recurrence. However, these clinical
      predictors alone are not as reliable as severity of early postoperative
      endoscopic recurrence in clinical practice. In ulcerative colitis (UC), extensive
      colitis at diagnosis is associated with unfavourable clinical course in the first
      5 to 10 years of the disease, and also with long-term colectomy and colorectal
      inflammation-associated colorectal cancer. In patients with extensive UC at
      diagnosis, a rapid step-up strategy aiming to achieve sustained deep remission
      should therefore be considered. At the moment, no reliable serological or genetic
      predictor of inflammatory bowel disease clinical course has been identified.

PMID- 22876032
TI  - Impact of environmental and dietary factors on the course of inflammatory bowel
      disease.
AB  - Besides their possible effects on the development of inflammatory bowel disease
      (IBD), some environmental factors can modulate the clinical course of both
      ulcerative colitis (UC) and Crohn's disease (CD). This review is mainly devoted
      to describing the current knowledge of the impact of some of these factors on the
      outcome of IBD, with special emphasis on smoking and diet. Although the impact of
      smoking on the susceptibility to develop CD and UC is firmly established, its
      influence on the clinical course of both diseases is still debatable. In CD,
      active smoking is a risk factor for postoperative recurrence. Beyond this
      clinical setting, smoking cessation seems to be advantageous in those CD patients
      who were smokers at disease diagnosis, while smoking resumption may be of benefit
      in ex-smokers with resistant UC. The role of dietary habits on the development of
      IBD is far from being well established. Also, food intolerances are very
      frequent, but usually inconsistent among IBD patients, and therefore no general
      dietary recommendations can be made in these patients. In general, IBD patients
      should eat a diet as varied as possible. Regarding the possible therapeutic role
      of some dietary components in IBD, lessons should be drawn from the investigation
      of the primary therapeutic effect of enteral nutrition in CD. Low-fat diets seem
      to be particularly useful. Also, some lipid sources, such as olive oil, medium
      chain triglycerides, and perhaps omega-3 fatty acids, might have a therapeutic
      effect. Fermentable fiber may have a role in preventing relapses in inactive UC.

PMID- 22876033
TI  - Impact of medical therapies on inflammatory bowel disease complication rate.
AB  - Crohn's disease and ulcerative colitis are progressive diseases associated with a
      high risk of complications over time including strictures, fistulae, perianal
      complications, surgery, and colorectal cancer. Changing the natural history and
      avoiding evolution to a disabling disease should be the main goal of treatment.
      In recent studies, mucosal healing has been associated with longer-term remission
      and fewer complications. Conventional therapies with immunosuppressive drugs are
      able to induce mucosal healing in a minority of cases but their impact on disease
      progression appears modest. Higher rates of mucosal healing can be achieved with
      anti-tumor necrosis factor therapies that reduce the risk of relapse, surgery and
      hospitalization, and are associated with perianal fistulae closure. These drugs
      might be able to change the natural history of the disease mainly when introduced
      early in the course of the disease. Treatment strategy in inflammatory bowel
      diseases should thus be tailored according to the risk that each patient could
      develop disabling disease.

PMID- 22876034
TI  - Surgery for Crohn's disease in the era of biologicals: a reduced need or delayed
      verdict?
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the
      entire gastrointestinal tract. Ultimately, up to 70% of all patients will need
      surgery, despite optimized medical therapy. Moreover, about half of the patients
      will need redo-surgery because of disease recurrence. The introduction of anti
      tumor necrosis factor (TNF) drugs (Infliximab in 1998) revolutionized the
      treatment of CD. Different randomized trials assessed the efficacy of anti-TNF
      treatment not only to induce, but also to maintain, steroid-free remission.
      Furthermore, these agents can rapidly lead to mucosal healing. This aspect is
      important, as it is a major predictor for long-term disease control. Subgroup
      analyses of responding patients seemed to suggest a reduction in the need for
      surgery at median-term follow up (1-3 years). However if one looks at population
      surveys, one does not observe any decline in the need for surgery since the
      introduction of Infliximab in 1998. The short follow-up term and the exclusion of
      patients with imminent surgical need in the randomized trials could bias the
      results. Only 60% of patients respond to induction of anti-TNF therapy, moreover,
      some patients will actually develop resistance to biologicals. Many patients are
      diagnosed when stenosing disease has already occurred, obviating the need for
      biological therapy. In a further attempt to change the actual course of the
      disease, top down strategies have been progressively implemented. Whether this
      will indeed obviate surgery for a substantial group of patients remains unclear.
      For the time being, surgery will still play a pivotal role in the treatment of
      CD.

PMID- 22876035
TI  - Role of surgery in severe ulcerative colitis in the era of medical rescue
      therapy.
AB  - Despite the growing use of medical salvage therapy, colectomy has remained a
      cornerstone in managing acute severe ulcerative colitis (ASC) both in children
      and in adults. Colectomy should be regarded as a life saving procedure in ASC,
      and must be seriously considered in any steroid-refractory patient. However,
      colectomy is not a cure for the disease but rather the substitution of a large
      problem with smaller problems, including fecal incontinence, pouchitis, irritable
      pouch syndrome, cuffitis, anastomotic ulcer and stenosis, missed or de-novo
      Crohn's disease and, in young females, reduced fecundity. This notion has led to
      the widespread practice of offering medical salvage therapy before colectomy in
      most patients without surgical abdomen or toxic megacolon. Medical salvage
      therapies which have proved effective in the clinical trial setting include
      cyclosporine, tacrolimus and infliximab, which seem equally effective in the
      short term. Validated predictive rules can identify a subset of patients who will
      eventually fail corticosteroid therapy after only 3-5 d of steroid therapy with
      an accuracy of 85%-95%. This accuracy is sufficiently high for initiating medical
      therapy, but usually not colectomy, early in the admission without delaying
      colectomy if required. This approach has reduced the colectomy rate in ASC from
      30%-70% in the past to 10%-20% nowadays, and the mortality rate from over 70% in
      the 1930s to about 1%. In general, restorative proctocolectomy (ileoanal pouch or
      ileal pouch-anal anastomosis), especially the J-pouch, is preferred over straight
      pull-through (ileo-anal) or ileo-rectal anastomosis, which may still be
      considered in young females concerned about infertility. Colectomy in the acute
      severe colitis setting, is usually performed in three steps due to the severity
      of the inflammation, concurrent steroid treatment and the generally reduced
      clinical condition. The first surgical step involves colectomy and constructing
      an ileal stoma, the second - constructing the pouch and the third - closing the
      stoma. This review focuses on the role of surgical treatment in ulcerative
      colitis in the era of medical rescue therapy.

PMID- 22876036
TI  - Colorectal cancer in inflammatory bowel disease: what is the real magnitude of
      the risk?
AB  - The association between inflammatory bowel disease (IBD) and colorectal cancer
      (CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in
      IBD. IBD-associated CRC (IBD-CRC) affects patients at a younger age than sporadic
      CRC. The prognosis for sporadic CRC and IBD-CRC is similar, with a 5-year
      survival of approximately 50%. Identifying at risk patients and implementing
      appropriate surveillance for these patients is central to managing the CRC risk
      in IBD. The increased risk of colorectal cancer in association with IBD is
      thought to be due to genetic and acquired factors. The link between inflammation
      and cancer is well recognised but the molecular biology, immune pathobiology and
      genetics of IBD-CRC are areas of much ongoing research. This review examines the
      literature relating to IBD-CRC, focusing on the incidence of IBD-CRC and
      examining potential risk factors including age at diagnosis, gender, duration and
      extent of colitis, severity of inflammation, family history of sporadic CRC and
      co-existent primary sclerosing cholangitis (PSC). Confirmed risk factors for IBD
      CRC are duration, severity and extent of colitis, the presence of co-existent PSC
      and a family history of CRC. There is insufficient evidence currently to support
      an increased frequency of surveillance for patients diagnosed with IBD at a
      younger age. Evidence-based guidelines advise surveillance colonoscopy for
      patients with colitis 8 to 10 years after diagnosis, with the interval for
      further surveillance guided by risk factors (extent of disease, family history of
      CRC, post-inflammatory polyps, concomitant PSC, personal history of colonic
      dysplasia, colonic strictures). There is a move away from using random colonic
      biopsies towards targeted biopsies aimed at abnormal areas identified by newer
      colonoscopic techniques (narrow band imaging, chromoendoscopy, confocal
      microendoscopy).

PMID- 22876037
TI  - Mutual regulation between microRNA-373 and methyl-CpG-binding domain protein 2 in
      hilar cholangiocarcinoma.
AB  - AIM: To investigate the reciprocal modulation between microRNA (miRNA) and DNA
      methylation via exploring the correlation between miR-373 and methyl-CpG-binding
      domain protein (MBD)2. METHODS: MiR-373 expression was examined using the TaqMan
      miRNA assay. Methylation of miR-373 was investigated using methylation-specific
      polymerase chain reaction, and recruitment of methyl binding proteins was studied
      using the chromatin immunoprecipitation assay. Mutation analysis was conducted
      using the QuikChangeTM Site-Directed Mutagenesis kit. The activity of miR-373
      gene promoter constructs and targeting at MBD2-three prime untranslated region
      (3'UTR) by miR-373 were evaluated by a dual-luciferase reporter gene assay.
      RESULTS: In hilar cholangiocarcinoma, miR-373 decreased and was closely
      associated with poor cell differentiation, advanced clinical stage, and shorter
      survival. The promoter-associated CpG island of miR-373 gene was hypermethylated
      and inhibited expression of miR-373. MBD2 was up-regulated and enriched at the
      promoter-associated CpG island of miR-373. Methylation-mediated suppression of
      miR-373 required MBD2 enrichment at the promoter-associated CpG island, and miR
      373 negatively regulated MBD2 expression through targeting the 3'UTR. CONCLUSION:
      MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2
      activity through a feedback loop of CpG island methylation.

PMID- 22876038
TI  - Moro orange juice prevents fatty liver in mice.
AB  - AIM: To establish if the juice of Moro, an anthocyanin-rich orange, may improve
      liver damage in mice with diet-induced obesity. METHODS: Eight-week-old mice were
      fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk.
      Liver morphology, gene expression of lipid transcription factors, and metabolic
      enzymes were assessed. RESULTS: Mice fed HFD displayed increased body weight,
      insulin resistance and dyslipidemia. Moro juice administration limited body
      weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and
      total cholesterol. Mice fed HFD showed liver steatosis associated with
      ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the
      expression of peroxisome proliferator-activated receptor-alpha and its target
      gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice
      consumption suppressed the expression of liver X receptor-alpha and its target
      gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase
      1 activity. CONCLUSION: Moro juice counteracts liver steatogenesis in mice with
      diet-induced obesity and thus may represent a promising dietary option for the
      prevention of fatty liver.

PMID- 22876039
TI  - A totally mini-invasive approach for colorectal laparoscopic surgery.
AB  - AIM: To study the short-term outcome of patients treated with laparoscopic right
      colectomy and how intracorporeal anastomosis has improved the outcome. METHODS:
      We retrospectively examined all patients affected by colorectal cancer who
      underwent a laparoscopic right colectomy between January 2006 and December 2010
      in our department. Our evaluation criteria were: diagnosis of colorectal
      carcinoma at presurgical biopsy, elective surgery, and the same surgeon. We
      excluded: emergency surgery, conversions from laparotomic colectomy, and other
      surgeons. The endpoints we examined were: surgical time, number of lymph nodes
      removed, length of stay (removal of nasogastric tube, bowel movements, gas
      evacuation, solid and liquid feeding, hospitalization), and major complications.
      Seventy-two patients were divided into two groups: intracorporeal anastomosis (39
      patients) and extracorporeal anastomosis (33 patients). RESULTS: Significant
      differences were observed between intracorporeal vs extracorporeal anastomosis,
      respectively, for surgical times (186.8 min vs 184.1 min, P < 0.001), time to
      resumption of gas evacuation (3 d vs 3.5 d, P < 0.001), days until resumption of
      bowel movements (3.8 d vs 4.9 d, P < 0.001), days until resumption of liquid diet
      (3.5 d vs 4.5 d, P < 0.001), days until resuming a solid diet (4.6 d vs 5.7 d, P
      < 0.001), and total hospitalization duration (7.4 d vs 8.5 d, P < 0.001). In the
      intracorporeal group, on average, 19 positive lymph nodes were removed; in the
      extracorporeal group, on average, 14 were removed P < 0.001). Thus,
      intracorporeal anastomosis for right laparoscopic colectomy improved patient
      outcome by providing faster recovery of nutrition, faster recovery of intestinal
      function, and shorter hospitalization than extracorporeal anastomosis.
      CONCLUSION: Short-term outcomes favor intracorporeal anastomosis, confirming that
      a less traumatic surgical approach improves patient outcome.

PMID- 22876040
TI  - A novel animal model for in vivo study of liver cancer metastasis.
AB  - AIM: To establish an animal model with human hepatocyte-repopulated liver for the
      study of liver cancer metastasis. METHODS: Cell transplantation into mouse livers
      was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells
      (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing
      urokinase-type plasminogen activator (uPA) driven by the albumin
      enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse
      line (uPA/SCID mice). Host mice were divided into two groups (A and B). Group A
      mice were transplanted with h-GCCs alone, and group B mice were transplanted with
      h-GCCs and h-hepatocytes together. The replacement index (RI), which is the ratio
      of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a
      histological section, was estimated by measuring h-AFP and h-albumin
      concentrations in sera, respectively, as well as by immunohistochemical analyses
      of h-AFP and human cytokeratin 18 in histological sections. RESULTS: The h-GCCs
      successfully engrafted, repopulated, and colonized the livers of mice in group A
      (RI = 22.0% +/- 2.6%). These mice had moderately differentiated
      adenocarcinomatous lesions with disrupted glandular structures, which is a
      characteristics feature of gastric cancers. The serum h-AFP level reached 211.0
      +/- 142.2 g/mL (range, 7.1-324.2 g/mL). In group B mice, the h-GCCs and h
      hepatocytes independently engrafted, repopulated the host liver, and developed
      colonies (RI = 12.0% +/- 6.8% and 66.0% +/- 12.3%, respectively). h-GCC colonies
      also showed typical adenocarcinomatous glandular structures around the h
      hepatocyte-colonies. These mice survived for the full 56 day-study and did not
      exhibit any metastasis of h-GCCs in the extrahepatic regions during the
      observational period. The mice with an h-hepatocyte-repopulated liver possessed
      metastasized h-GCCs and therefore could be a useful humanized liver animal model
      for studying liver cancer metastasis in vivo. CONCLUSION: A novel animal model of
      human liver cancer metastasis was established using the uPA/SCID mouse line. This
      model could be useful for in vivo testing of anti-cancer drugs and for studying
      the mechanisms of human liver cancer metastasis.

PMID- 22876041
TI  - Endoscopic ultrasound-guided fine needle aspiration in the differentiation of
      type 1 and type 2 autoimmune pancreatitis.
AB  - AIM: To investigate the usefulness of endoscopic ultra-sound-guided fine needle
      aspiration (EUS-FNA) in the differentiation of autoimmune pancreatitis (AIP).
      METHODS: We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA
      and met the Asian diagnostic criteria. On 47 EUS-FNA specimens, we evaluated the
      presence of adequate material and characteristic features of lymphoplasmacytic
      sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP)
      mentioned in the International Consensus Diagnostic Criteria and examined if
      these findings make a contribution to the differential diagnosis of type 1 and
      type 2 AIP. A disposable 22-gauge needle was used for EUS-FNA. RESULTS: Adequate
      specimens including pancreatic tissue for differentiating AIP from cancer were
      obtained from 43 of 47 patients who underwent EUS-FNA. EUS-FNA was performed from
      the pancreatic head in 21 cases, which is known to be technically difficult when
      performed by core biopsy; there was no significant difference in the results
      compared with pancreatic body-tail. Nine of 47 patients met level 1 findings of
      LPSP and 5 patients met level 2 findings of LPSP. No one met level 1 findings of
      IDCP, but 3 patients met level 2 findings of IDCP. Of 10 seronegative cases, 2
      cases were diagnosed with "definitive type 1 AIP", and 3 cases were diagnosed
      with "probable type 2 AIP" when considering both the level 2 histological
      findings and response to steroids. CONCLUSION: EUS-FNA is useful in the
      differentiation of type 1 and type 2 AIP, particularly in seronegative cases.

PMID- 22876042
TI  - Non-invasive determination of hepatic steatosis by acoustic structure
      quantification from ultrasound echo amplitude.
AB  - AIM: To use leptin-deficient (ob/ob) mice with demonstrated differences in
      steatosis levels to test a new diagnostic method using the acoustical structure
      quantification (ASQ) mode and the associated analytical parameter, "focal
      disturbance ratio" (FD-ratio). METHODS: Nine ob/ob mice, at 5, 8, and 12 wk of
      age (n = 3 in each age group), were used as models for hepatic steatosis. Echo
      signals obtained from ultrasonography in the mice were analyzed by ASQ, which
      uses a statistical analysis of echo amplitude to estimate inhomogeneity in the
      diagnostic region. FD-ratio, as calculated from this analysis, was the focus of
      the present study. FD-ratio and fat droplet areas and sizes were compared between
      age groups. RESULTS: No fibrosis or inflammation was observed in any of the
      groups. The fat droplet area significantly (P < 0.01) increased with age from
      1.25% +/- 0.28% at 5 wk to 31.07% +/- 0.48% at 8 wk to 51.69% +/- 3.19% at 12 wk.
      The median fat droplet size also significantly (P < 0.01) increased with age,
      from 1.33 (0.55-10.52) MUm at 5 wk, 2.82 (0.61-44.13) MUm at 8 wk and 6.34 (0.66
      81.83) MUm at 12 wk. The mean FD-ratio was 0.42 +/- 0.11 at 5 wk, 0.11 +/- 0.05
      at 8 wk, and 0.03 +/- 0.02 at 12 wk. The FD-ratio was significantly lower at 12
      wk than at 5 wk and 8 wk (P < 0.01). A significant negative correlation was
      observed between the FD-ratio and either the fat droplet area (r = -0.7211, P =
      0.0017) or fat droplet size (r = -0.9811, P = 0.0052). CONCLUSION: This tool for
      statistical analysis of signals from ultrasonography using the FD-ratio can be
      used to accurately quantify fat in vivo in an animal model of hepatic steatosis,
      and may serve as a quantitative biomarker of hepatic steatosis.

PMID- 22876043
TI  - Differential roles of EPS8 in carcinogenesis: loss of protein expression in a
      subset of colorectal carcinoma and adenoma.
AB  - AIM: To analyze the epidermal growth factor receptor pathway substrate 8 (EPS8)
      expression status and role in colorectal carcinogenesis given that EPS8 has a
      conserved actin barbed-end capping function that is required for proper
      maturation in intestinal cells. METHODS: We studied 8 colon cancer cell lines and
      58 colorectal tumors (19 adenomas and 39 carcinomas). We performed expression
      microarray analysis of colon cancer cell lines followed by loss of heterozygosity
      (LOH) analysis and immunohistochemistry for EPS8 expression in colon tumors.
      Subsequently, we performed mutation analysis by direct sequencing and methylation
      analysis by bisulfite sequencing and methylation-specific polymerase chain
      reaction assays. RESULTS: Expression microarray analysis of colon cancer cell
      lines showed overexpression of EPS8 transcript in all lines but RKO. Genome wide
      loss of heterozygosity (LOH) analysis of colon tumors, showed considerable LOH at
      the EPS8 gene locus. Immunohistochemically, EPS8 was constitutively expressed in
      normal colonic mucosa with a dot-like supranuclear localization with accentuation
      at the luminal surface supporting its proposed role in epithelial maturation.
      Nineteen colon tumors (4 adenoma, 15 carcinoma) out of 51 (37%) showed strikingly
      tumor specific EPS8 protein loss. Of the remaining tumors, 5/51 (2 adenoma, and 3
      carcinoma, 10%) showed marked overexpression, while 27/51 tumors (53%) showed
      retained expression. Mutation analysis revealed a missense mutation (c.794C>T,
      p.R265C) in exon 8 in RKO. The EPS8 promoter was also methylated in RKO, but
      there was no significant methylation in other cell lines or carcinoma specimens.
      CONCLUSION: The loss of EPS8 expression in colorectal adenomas and carcinomas
      suggests that down regulation of this gene contributes to the development of a
      subset of colorectal cancers, a finding which could have applications in
      diagnosis and treatment.

PMID- 22876044
TI  - Choice of approach for hepatectomy for hepatocellular carcinoma located in the
      caudate lobe: isolated or combined lobectomy?
AB  - AIM: To investigate the significance of the surgical approaches in the prognosis
      of hepatocellular carcinoma (HCC) located in the caudate lobe with a multivariate
      regression analysis using a Cox proportional hazard model. METHODS: Thirty-six
      patients with HCC underwent caudate lobectomy at a single tertiary referral
      center between January 1995 and June 2010. In this series, left-sided, right
      sided and bilateral approaches were used. The outcomes of patients who underwent
      isolated caudate lobectomy or caudate lobectomy combined with an additional
      partial hepatectomy were compared. The survival curves of the isolated and
      combined resection groups were generated by the Kaplan-Meier method and compared
      by a log-rank test. RESULTS: Sixteen (44.4%) of 36 patients underwent isolated
      total or partial caudate lobectomy whereas 20 (55.6%) received a total or partial
      caudate lobectomy combined with an additional partial hepatectomy. The median
      diameter of the tumor was 6.7 cm (range, 2.1-15.8 cm). Patients who underwent an
      isolated caudate lobectomy had significantly longer operative time (240 min vs
      170 min), longer length of hospital stay (18 d vs 13 d) and more blood loss (780
      mL vs 270 mL) than patients who underwent a combined caudate lobectomy (P <
      0.05). There were no perioperative deaths in both groups of patients. The
      complication rate was higher in the patients who underwent an isolated caudate
      lobectomy than in those who underwent combined caudate lobectomy (31.3% vs 10.0%,
      P < 0.05). The 1-, 3- and 5-year disease-free survival rates for the isolated
      caudate lobectomy and the combined caudate lobectomy groups were 54.5%, 6.5% and
      0% and 85.8%, 37.6% and 0%, respectively (P < 0.05). The corresponding overall
      survival rates were 73.8%, 18.5% and 0% and 93.1%, 43.6% and 6.7% (P < 0.05).
      CONCLUSION: The caudate lobectomy combined with an additional partial hepatectomy
      is preferred because this approach is technically less demanding and offers an
      adequate surgical margin.

PMID- 22876045
TI  - Normal carcinoembryonic antigen indicates benefit from perioperative chemotherapy
      to gastric carcinoma patients.
AB  - AIM: To evaluate pretreatment serum carcinoembryonic antigen (CEA) as a predictor
      of survival for patients with locally advanced gastric cancer receiving
      perioperative chemotherapy. METHODS: We retrospectively studied a cohort of 228
      gastric cancer patients who underwent D2 gastrectomy combined with chemotherapy
      at the Sun Yat-sen University Cancer Center between January 2005 and December
      2009. Among them, 168 patients received 6-12 cycles of oxaliplatin-based adjuvant
      (post-operative) chemotherapy, while 60 received perioperative chemotherapy (2
      cycles of FOLFOX6 or XELOX before surgery and 4-10 cycles after surgery). Serum
      CEA was measured using an enzyme immunoassay. The follow-up lasted until December
      2010. RESULTS: In the group that had elevated serum CEA, the difference in
      survival time between patients receiving perioperative chemotherapy and those
      receiving adjuvant chemotherapy had no statistical significance (P > 0.05).
      However, in the group that had normal serum CEA, patients receiving perioperative
      chemotherapy had a longer survival time. In multivariate analysis, T staging and
      lymph node metastatic rate were independent prognostic factors for the patients.
      Perioperative chemotherapy improved the overall survival of patients who had a
      normal pretreatment CEA level (P = 0.070). CONCLUSION: Normal pretreatment serum
      CEA is a predictor of survival for patients receiving perioperative chemotherapy.

PMID- 22876046
TI  - Thrombosis of celiacomesenteric trunk: report of a case.
AB  - Here we present the case of a 79-year-old woman who complained of acute abdominal
      pain, vomiting and diarrhoea. Laboratory exams demonstrated a severe metabolic
      imbalance. Abdominal X-rays showed bowel overdistension and pneumatosis of the
      stomach wall. Abdominal tomography revealed infarction of the stomach, duodenum
      and small bowel due to thrombosis of the celiacomesenteric trunk. Exploratory
      laparotomy revealed ischemia of the liver, spleen infarction and necrosis of the
      gastro-intestinal tube (from the stomach up to the first third of the transverse
      colon). No further surgical procedures were performed. The patient died the
      following day. To our knowledge, this is the first reported case about severe
      gastro-intestinal ischemia due to thrombosis of the celiacomesenteric trunk, a
      rare anatomic variation of the gastrointestinal vascularisation.

PMID- 22876047
TI  - Opioid/naloxone prolonged release combinations for opioid induced constipation.
AB  - I read with great interest the recent article by Chen et al in a recent issue of
      your esteemed journal. The article is highly thought provoking. One emerging
      therapeutic alternative for opioid induced constipation is the emergence of
      opioid/naloxone prolonged release combinations. For instance, naloxone when
      administered in a 1:2 ratio with oxycodone reverses the inhibitory effect of
      oxycodone on the gastrointestinal tract. The advantage of oxycodone/naloxone
      prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent
      to that of oxycodone prolonged release (OXC), it significantly decreases the
      "Bowel Function Index" thereby ameliorating symptoms of opioid induced
      constipation to a large extent. Schutter et al in a recent study have reported a
      decrease in the bowel function index from 38.2 to 15.1. Similarly, Lowenstein et
      al in another recent study have reported that following a month of therapy,
      complete spontaneous bowel movements per week is increased from one in OXC
      therapy to three in OXN therapy.

PMID- 22876049
TI  - Portable document format file showing the surface models of cadaver whole body.
AB  - In the Visible Korean project, 642 three-dimensional (3D) surface models have
      been built from the sectioned images of a male cadaver. It was recently
      discovered that popular PDF file enables users to approach the numerous surface
      models conveniently on Adobe Reader. Purpose of this study was to present a PDF
      file including systematized surface models of human body as the beneficial
      contents. To achieve the purpose, fitting software packages were employed in
      accordance with the procedures. Two-dimensional (2D) surface models including the
      original sectioned images were embedded into the 3D surface models. The surface
      models were categorized into systems and then groups. The adjusted surface models
      were inserted to a PDF file, where relevant multimedia data were added. The
      finalized PDF file containing comprehensive data of a whole body could be
      explored in varying manners. The PDF file, downloadable freely from the homepage
      (http://anatomy.co.kr), is expected to be used as a satisfactory self-learning
      tool of anatomy. Raw data of the surface models can be extracted from the PDF
      file and employed for various simulations for clinical practice. The technique to
      organize the surface models will be applied to manufacture of other PDF files
      containing various multimedia contents.

PMID- 22876048
TI  - Korean clinical practice guidelines: otitis media in children.
AB  - Acute otitis media (AOM) and otitis media with effusion (OME) are common
      infections in children, and their diagnosis and treatment have significant
      impacts on the health of children and the costs of providing national medical
      care. In 2009, the Korean Otologic Society organized a committee composed of
      experts in the field of otolaryngology, pediatrics, and family medicine to
      develop Korean clinical practice guidelines (CPG) for otitis media in children
      with the goal of meeting regional medical and social needs in Korea. For this
      purpose, the committee adapted existing guidelines. A comprehensive literature
      review was carried out primarily from 2004 to 2009 using medical search engines
      including data from Korea. A draft was written after a national questionnaire
      survey and several public audits, and it was editorially supervised by senior
      advisors before publication of the final report. These evidence-based guidelines
      for the management of otitis media in children provide recommendations to primary
      practitioners for the diagnosis and treatment of children younger than 15 yr old
      with uncomplicated AOM and OME. The guidelines include recommendations regarding
      diagnosis, treatment options, prevention and parent education, medical records,
      referral, and complementary/alternative medicine for treating pediatric otitis
      media.

PMID- 22876050
TI  - Isolation and characterization of chorionic mesenchymal stromal cells from human
      full term placenta.
AB  - This study focused on the characterization of mesenchymal stromal cells (MSCs)
      from the chorion of human full term placenta from 15 donors. Chorionic MSCs
      revealed homologous fibroblast-like morphology and expressed CD73, CD29, CD105,
      and CD90. The hematopoietic stem cell markers including HLA DR, CD11b, CD34,
      CD79a, and CD45 were not expressed. The growth kinetics of their serial passage
      was steady at the later passages (passage 10). The multilineage capability of
      chorionic MSCs was demonstrated by successful adipogenic, osteogenic and
      chondrogenic differentiation and associated gene expression. Chorionic MSCs
      expressed genes associated with undifferentiated cells (NANOG, OCT4, REX1) and
      cardiogenic or neurogenic markers such as SOX2, FGF4, NES, MAP2, and NF. TERT was
      negative in all the samples. These findings suggest that chorionic MSCs
      undifferentiated stem cells and less likely to be transformed into cancer cells.
      A low HLA DR expression suggests that chorionic MSCs may serve as a great source
      of stem cells for transplantation because of their immune-privileged status and
      their immunosuppressive effect. Based on these unique properties, it is concluded
      that chorionic MSCs are pluripotent stem cells that are probably less
      differentiated than BM-MSCs, and they have considerable potential for use in cell
      based therapies.

PMID- 22876051
TI  - Factors related to prehospital time delay in acute ST-segment elevation
      myocardial infarction.
AB  - Despite recent successful efforts to shorten the door-to-balloon time in patients
      with acute ST-segment elevation myocardial infarction (STEMI), prehospital delay
      remains unaffected. Nonetheless, the factors associated with prehospital delay
      have not been clearly identified in Korea. We retrospectively evaluated 423
      patients with STEMI. The mean symptom onset-to-door time was 255 +/- 285 (median:
      150) min. The patients were analyzed in two groups according to symptom onset-to
      door time (short delay group: <= 180 min vs long delay group: > 180 min).
      Inhospital mortality was significantly higher in long delay group (6.9% vs 2.8%;
      P = 0.048). Among sociodemographic and clinical variables, diabetes, low
      educational level, triage via other hospital, use of private transport and night
      time onset were more prevalent in long delay group (21% vs 30%; P = 0.038, 47% vs
      59%; P = 0.013, 72% vs 82%; P = 0.027, 25% vs 41%; P < 0.001 and 33% vs 48%; P =
      0.002, respectively). In multivariate analysis, low educational level (1.66 [1.08
      2.56]; P = 0.021), symptom onset during night time (1.97 [1.27-3.04]; P = 0.002),
      triage via other hospital (1.83 [1.58-5.10]; P = 0.001) and private transport
      were significantly associated with prehospital delay (3.02 [1.81-5.06]; P <
      0.001). In conclusion, prehospital delay is more frequent in patients with low
      educational level, symptom onset during night time, triage via other hospitals,
      and private transport, and is associated with higher inhospital mortality.

PMID- 22876052
TI  - Abdominal aortic calcification is associated with diastolic dysfunction,
      mortality, and nonfatal cardiovascular events in maintenance hemodialysis
      patients.
AB  - This study evaluated the significance of aortic calcification index (ACI), an
      estimate of abdominal aortic calcification by plain abdominal computed tomography
      (CT), in terms of left ventricular (LV) diastolic dysfunction, mortality, and
      nonfatal cardiovascular (CV) events in chronic hemodialysis patients.
      Hemodialysis patients who took both an abdominal CT and echocardiography were
      divided into a low-ACI group (n = 64) and a high-ACI group (n = 64). The high-ACI
      group was significantly older, had a longer dialysis vintage and higher
      comorbidity indices, and more patients had a previous history of CV disease than
      the low-ACI group. The ACI was negatively correlated with LV end-diastolic volume
      or LV stroke volume, and was positively correlated with the ratio of peak early
      transmitral flow velocity to peak early diastolic mitral annular velocity (E/E'
      ratio), a marker of LV diastolic function. The E/E' ratio was independently
      associated with the ACI. The event-free survival rates for mortality and nonfatal
      CV events were significantly lower in the high-ACI group compared with those in
      the low-ACI group, and the ACI was an independent predictor for all-cause deaths
      and nonfatal CV events. In conclusion, ACI is significantly associated with
      diastolic dysfunction and predicts all-cause mortality and nonfatal CV events in
      hemodialysis patients.

PMID- 22876053
TI  - Direct medical costs for patients with type 2 diabetes and related complications:
      a prospective cohort study based on the Korean National Diabetes Program.
AB  - We analyzed the direct medical costs for Korean patients with type 2 diabetes
      according to the type of complications and the number of microvascular
      complications. We analyzed costs for type 2 diabetes and associated complications
      in 3,125 patients. These data were obtained from the Korean National Diabetes
      Program (KNDP), a large, ongoing, prospective cohort study that began in 2005.
      The cost data were prospectively collected, using an electronic database, for the
      KNDP cohort at six hospitals. The costs were analyzed according to complications
      for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no
      vascular complications; 1,883 had microvascular complications only; 51 had
      macrovascular complications only; and 273 had both complications. The annual
      direct medical costs for a patient with only macrovascular, only microvascular,
      or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0
      times higher than the medical costs of patients without complications. Annual
      direct medical costs per patient increased with the number of microvascular
      complications in patients without macrovascular complications. The economic costs
      for type 2 diabetes are attributable largely to the management of microvascular
      and macrovascular complications. Proper management of diabetes and prevention of
      related complications are important for reducing medical costs.

PMID- 22876054
TI  - Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma:
      clinical manifestation and prognostic outcome.
AB  - The study aimed to identify the clinical characteristics of coexisting chronic
      lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to
      evaluate the influence on prognosis. A total of 1,357 patients who underwent
      thyroid surgery for PTC were included. The clinicopathological characteristics
      were identified. Patients who underwent total thyroidectomy (n = 597) were
      studied to evaluate the influence of coexistent CLT on prognosis. Among the total
      1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence
      of females was higher than in the control group without CLT (P < 0.001). Mean
      tumor size and mean age in the patients with CLT were smaller than without CLT (P
      = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with
      CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597
      patients, disease-free survival rate in the patients with CLT was significantly
      higher than without CLT (P = 0.042). However, the multivariate analysis did not
      reveal a negative association between CLT coexistence and recurrence. Patients
      with CLT display a greater female preponderance, smaller size, younger and lower
      extrathyroidal extension. CLT is not a significant independent negative
      predictive factor for recurrence, although presence of CLT indicates a reduced
      risk of recurrence.

PMID- 22876055
TI  - Preoperative predictive factors for parathyroid carcinoma in patients with
      primary hyperparathyroidism.
AB  - This study was conducted to review the clinical characteristics of parathyroid
      carcinoma (PC) and to evaluate potential preoperative predictive factors for PC
      in patients with primary hyperparathyroidism (PHPT). We performed a retrospective
      review of electronic medical records of 194 patients with pathologically
      confirmed PHPT in affiliated teaching hospitals of Seoul National University from
      January 2000 to March 2011. Adenoma was diagnosed in 171 patients, hyperplasia in
      12, and carcinoma in 11. Several biochemical measurements were higher in patients
      with PC than in patients with benign disease, including serum total calcium (P <
      0.001), intact parathyroid hormone (P = 0.003), and alkaline phosphatase (ALP) (P
      < 0.001). Tumors were larger in PC than in benign disease (P < 0.001).
      Multivariate analysis revealed that serum ALP level (P < 0.001) and tumor size
      were associated with PC (P = 0.03). Tumor size and serum ALP level were evaluated
      as preoperative predictive factors for PC using ROC analyses: a tumor size of 3.0
      cm (sensitivity 90.9%, specificity 92.1%) and serum ALP level of 285 IU/L (83.3%,
      97.0%) had predictive value for the diagnosis of PC in patients with PHPT. In
      conclusion, elevated serum ALP and a large parathyroid mass at the time of
      diagnosis can be helpful to predict PC in patients with PHPT.

PMID- 22876056
TI  - Mycobacterial pulmonary infections in patients with idiopathic pulmonary
      fibrosis.
AB  - Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for
      developing tuberculosis (TB). However, no studies have been reported regarding
      the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We
      reviewed 795 patients with IPF from five university hospitals who were diagnosed
      by histological or radio-clinical criteria. In the 795 patients with IPF,
      pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in
      35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than
      that found in the general population. TB was more common in patients treated with
      immunosuppressants than in those who did not receive immunosuppressants (2.6% vs
      1.4%, P = 0.12). Among the IPF patients who had mycobacterial
      infections,immunosuppressant users developed TB or NTMLD within 1 yr after
      treatment with immunosuppressants,while those occurred later than 2 yr after
      diagnosis of IPF in the subjects that did not receive immunosuppressants. Among
      51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up.
      Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD
      is relatively common in patients with IPF in Korea and may be fatal in some
      groups. Careful evaluation of TB and NTMLD is necessary not only for
      immunosuppressant users, but also for nonusers with IPF.

PMID- 22876057
TI  - Comorbidities of chronic obstructive pulmonary disease in Koreans: a population
      based study.
AB  - Chronic obstructive pulmonary disease (COPD) includes pulmonary components with
      increased comorbidity rates, as well as being a systemic disease. Comorbidities
      may frequently occur in COPD patients over 40 yr old. We report the comorbidities
      of patients with COPD, diagnosed by spirometry, in a population-based
      epidemiologic survey in Korea. Data were derived from the fourth Korean Health
      and Nutrition Examination Survey in 2008, a stratified multistage clustered
      probability design survey of a sample representing the entire population of
      Korea. Results of spirometry and various health-related questionnaires were
      analyzed in 2,177 subjects aged >= 40 yr. The prevalence of COPD (FEV(1)/FVC <
      0.7) in subjects >= 40 yr of age was 14.1%. Multivariate analysis showed that
      underweight (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.05-8.98),
      coronary heart disease (OR, 0.43; 95% CI, 0.20-0.93) and dyslipidemia (OR, 0.61;
      95% CI, 0.45-0.82) were significantly associated with COPD, whereas allergic
      rhinitis, anemia, arthritis, chronic renal failure, depression, diabetes
      mellitus, hypertension, gastrointestinal ulcer, and osteoporosis were not.
      Underweight might be more prevalent but coronary heart disease and dyslipidemia
      are less prevalent in Koreans with than without COPD in population setting.

PMID- 22876058
TI  - Minor criteria of Infectious Disease Society Of America/American Thoracic Society
      for severe community-acquired pneumonia can predict delayed treatment response.
AB  - The purpose of this study was to investigate the clinical aspects of patients
      satisfying the Infectious Disease Society of America/American Thoracic Society
      (IDSA/ATS) minor severity criteria, focusing on their treatment response to
      empirical antibiotics. In total, 381 community-acquired pneumonia (CAP) patients
      who did not require mechanical ventilation or vasopressors at admission were
      enrolled, and 50 (13.1%) satisfied the minor severity criteria (i.e. , minor
      severe CAP [minor-SCAP]). The rates of new complication events and clinical
      treatment failure were significantly higher in the minor-SCAP group than in the
      control group (30.0% vs 2.1%, P < 0.001, and 42.0% vs 10.6%, P < 0.001,
      respectively), and the time to reach clinical stability was longer in the minor
      SCAP group (8 days vs 3 days, P < 0.001). In a multivariate model, minor severity
      criteria (>= 3) were significantly associated with treatment failure (odds ratio,
      2.838; 95% confidence interval, 1.216 to 6.626), and for predicting treatment
      failure the value of the area under the receiver operating characteristic curve
      for minor criteria was 0.731, similar to other established scoring methods. The
      IDSA/ATS minor severity criteria can predict delayed treatment response and
      clinical treatment failure.

PMID- 22876059
TI  - Incidence of bronchopulmonary dysplasia in Korea.
AB  - A nationwide survey was conducted to determine the incidence of bronchopulmonary
      dysplasia (BPD) in Korea and the intercenter differences in survival and BPD
      rates among preterm infants. Questionnaires were sent to all registered neonatal
      intensive care units (NICUs). The questionnaires inquired about the survival and
      BPD rates of very low birth weight (VLBW, < 1,500 g) infants who had been
      admitted to each NICU from 2007 to 2008. BPD was defined as requiring oxygen at
      36 weeks' postmenstrual age. Almost all level III NICUs replied. During the study
      period, 3,841 VLBW infants were born in the NICUs that responded to the survey.
      The survival rate was 81% and the BPD rate was 18%. Combined outcome of BPD or
      death rate was 37%. The BPD rate and combined outcome of BPD or death rate varied
      considerably from 5% to 50% and 11% to 73%, respectively across the centers.
      There was no significant correlation between the survival rate and the BPD rate
      across the centers. In conclusion, the incidence of BPD among VLBW infants in
      Korea during the study period was 18%, and a considerable intercenter difference
      in BPD rates was noted.

PMID- 22876060
TI  - Prevalence and seroprevalence of low-risk human papillomavirus in Korean women.
AB  - Little is known about the prevalence and seroprevalence of low-risk human
      papillomavirus (HPV) and the risk factors for HPV infection in Korean women. We
      determined the prevalence of low-risk HPV among 902 women aged 20-59 yr and the
      seroprevalence of low-risk HPV subtypes 6 and 11 among 1,094 women aged 9-59 yr
      in the general population. Genital low-risk HPV DNA was assessed by liquid
      hybridization and polymerase chain reaction. Antibody titers against HPV 6 and 11
      were measured by a multiplexed competitive luminex technique. The prevalence of
      genital low-risk HPV was 4.9%. It reached its highest peak of 10.3% at 20-29 yr
      of age and a second peak of 3.2% at 50-59 yr of age. The seroprevalence of HPV 6
      or 11 was 9.4%. It reached its highest peak of 12.7% at 25-29 yr of age and a
      second peak of 12.3% at 50-59 yr of age. In multivariable analysis, the number of
      lifetime sexual partners and past history of sexually transmitted diseases were
      associated with the seroprevalence but not prevalence of HPV. It is suggested
      that younger women should receive prophylactic HPV vaccination before they become
      sexually active and exposed to HPV in their 20s. This study provides baseline
      data for developing HPV vaccination programs and monitoring vaccine efficacy in
      Korea.

PMID- 22876061
TI  - Relationship between complex regional pain syndrome and working life: a Korean
      study.
AB  - Complex regional pain syndrome affects the quality of life of the patient. The
      aim of this study was to investigate the epidemiological features of this
      syndrome and evaluate its effect on the patient's working life. We demonstrated
      that the disease has a male preponderance and is 3 times more likely to affect
      the lower extremities. In this study, 11 participants (20%) retained their
      employment, whereas 44 (80%) became unemployed. Mean age and pain score were
      lower in the employment group than in the unemployment group (29.1 +/- 16.8 yr vs
      40.1 +/- 12.6 yr, P = 0.021, and 4.5 +/- 2.9 vs 7.0 +/- 2.0, P = 0.002,
      respectively). Subjects diagnosed within 8 months (P = 0.044), those who had
      achieved higher levels of education (P = 0.028), and those working in white
      collar jobs (P = 0.011) had higher employment-retention rates. Therefore,
      patients must manage their jobs (lower physical demand and decrease the number of
      working hours) if they are to improve their occupational life. To achieve
      satisfactory outcomes and a high employment-retention rate, clinicians must be
      aware of the importance of an early diagnosis (within 8 months), appropriate
      treatment, and a reduction in the patient's pain score.

PMID- 22876062
TI  - Influences on formation of tetanus antibody after simultaneous injection of
      tetanus immunoglobulin with tetanus vaccine.
AB  - The goal of this study was to determine how much the formation of tetanus
      antibody is influenced after a single injection of tetanus vaccine (Td) and the
      simultaneous injection of tetanus vaccine with tetanus immunoglobulin (TIG). All
      of the healthy adult volunteers were divided into two groups: group 1 (Td only)
      and group 2 (Td plus TIG). Two hundred thirty seven volunteers were enrolled.
      When the baseline antibody titer, gender and age were adjusted, the geometric
      mean titers (GMTs) of the tetanus antibody (group 1 vs group 2) was 0.8438 IU/mL
      vs 0.5684 IU/mL at 4 weeks (P = 0.002), 0.4074 IU/mL vs 0.3217 IU/mL at 6 months
      (P = 0.072) and 0.3398 IU/mL vs 0.2761 IU/mL at 12 months (P = 0.140) after
      injection, respectively. The formation of tetanus antibody after tetanus
      vaccination is not influenced by TIG at the late period and in adults below the
      age of 50 yr, but there are significant differences between the two groups at the
      early period of 4 weeks after vaccination and for the patients over 60 yr.

PMID- 22876063
TI  - Risk factors for occurrence and 30-day mortality for carbapenem-resistant
      Acinetobacter baumannii bacteremia in an intensive care unit.
AB  - To assess the risk factors for carbapenem-resistant Acinetobacter baumannii
      (CRAB) bacteremia and for 30-day mortality in patients with CRAB bacteremia in
      the intensive care unit (ICU), we conducted a retrospective study in the ICU at
      Severance Hospital in Korea from January 2008 to December 2009. Patients who
      acquired CRAB bacteremia in the ICU were enrolled as the case group and patients
      whose specimens of blood culture, sputum/endotracheal aspirate and urine revealed
      no AB were enrolled as controls. The case group comprised 106 patients and 205
      patients were included as controls. Risk factors independently associated with
      CRAB bacteremia included prior chemotherapy or radiotherapy treatment (Odds ratio
      [OR], 3.6; P = 0.003), recent central venous catheter insertion (OR, 5.7; P <
      0.001) or abdominal drainage insertion (OR, 21.9; P = 0.004), the number of
      antibiotics treated with (OR, 1.3; P = 0.016), and respiratory failure in the ICU
      (OR, 2.5; P = 0.035). The 30-day mortality was 79.8%. Renal failure during ICU
      stay was independently associated with 30-day mortality (OR, 3.7; P = 0.047). It
      is important to minimize invasive procedures, and to restrict excessive use of
      antibiotics, especially in immunocompromised patients, in order to prevent the
      development of CRAB bacteremia. Greater concern for CRAB bacteremia patients is
      needed when renal failure develops during ICU stay.

PMID- 22876064
TI  - Mosaic ring chromosome 6 in an infant with significant patent ductus arteriosus
      and multiple congenital anomalies.
AB  - The clinical features of ring chromosome 6 include central nervous system
      anomalies, growth retardation, facial dysmorphism and other congenital anomalies.
      Ring chromosome 6 occurs rarely and manifests as various phenotypes. We report
      the case of mosaic ring chromosome 6 by conventional karyotyping in a 7-day-old
      male infant diagnosed with a large patent ductus arteriosus (PDA) with hypoplasia
      of aortic valve and aortic arch. These have not been previously reported with
      ring chromosome 6. He recovered from heart failure symptoms after ligation of the
      PDA. He showed infantile failure to thrive and delayed milestone in a follow-up
      evaluation. To the best of our knowledge, this is the first report of a Korean
      individual with ring chromosome 6 and hemodynamically significant PDA.

PMID- 22876065
TI  - Rupture of right hepatic duct into hydatid cyst.
AB  - Echinococcal disease can develop anywhere in the human body. The liver represents
      its most frequent location. Hepatic hydatid cysts may rupture into the biliary
      tract, thorax, peritoneum, viscera, digestive tract or skin. We report a rare
      case with rupture of the right hepatic duct into a hydatid cyst in a woman with
      known hydatid disease and choledocholithiasis. The increased intra-luminal
      pressure in the biliary tree caused the rupture into the adjacent hydatid cyst.
      The creation of the fistula between the right hepatic duct and the hydatid cyst
      decompressed the biliary tree, decreased the bilirubin levels and offered a
      temporary resolution of the obstructive jaundice. Rupture of a hydatid cyst into
      the biliary tree usually leads to biliary colic, cholangitis and jaundice.
      However, in case of obstructive jaundice due to choledocholithiasis, it is
      possible that the cyst may rupture by other way around while offering the patient
      a temporary relief from his symptoms.

PMID- 22876066
TI  - A case of elderly-onset Crescentic Henoch-Schonlein purpura nephritis with
      hypocomplementemia and positive MPO-ANCA.
AB  - Henoch-Schonlein purpura (HSP) is common in childhood and often self-limiting.
      There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr
      old man was transferred to our hospital with a 1-month history of oliguria,
      abdominal pain, edema and palpable purpura in the legs. Three months ago, he was
      admitted to another hospital with jaundice, and consequently diagnosed with early
      common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics
      were administrated because of leakage in the suture from the surgery. However, he
      showed progressive renal failure with edema and purpura in the legs. Laboratory
      investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141
      mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40
      and C(3) below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as
      well as mesangial and extracapillary Ig A deposition. We started steroid therapy
      and hemodialysis, but he progressed to end-stage renal failure and he has been
      under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can
      be crescentic glomerulonephritis rapidly progressed to end stage renal failure.

PMID- 22876067
TI  - The first Korean case of lysinuric protein intolerance: presented with short
      stature and increased somnolence.
AB  - Lysinuric protein intolerance (LPI) is a rare inherited metabolic disease, caused
      by defective transport of dibasic amino acids. Failure to thrive,
      hepatosplenomegaly, hematological abnormalities, and hyperammonemic crisis are
      major clinical features. However, there has been no reported Korean patient with
      LPI as of yet. We recently encountered a 3.7-yr-old Korean girl with LPI and the
      diagnosis was confirmed by amino acid analyses and the SLC7A7 gene analysis. Her
      initial chief complaint was short stature below the 3rd percentile and increased
      somnolence for several months. Hepatosplenomegaly was noted, as were anemia,
      leukopenia, elevated levels of ferritin and lactate dehydrogenase, and
      hyperammonemia. Lysine, arginine, and ornithine levels were low in plasma and
      high in urine. The patient was a homozygote with a splicing site mutation of
      IVS4+1G > A in the SLC7A7. With the implementation of a low protein diet, sodium
      benzoate, citrulline and L-carnitine supplementation, anemia, hyperferritinemia,
      and hyperammonemia were improved, and normal growth velocity was observed.

PMID- 22876068
TI  - Bromocriptine for control of hyperthermia in a patient with mixed autonomic
      hyperactivity after neurosurgery: a case report.
AB  - Mixed autonomic hyperactivity disorder (MAHD) among patients with acquired brain
      injury can be rare. A delayed diagnosis of MAHD might exacerbate the clinical
      outcome and increase healthcare expenses with unnecessary testing. However, MAHD
      is still an underrecognized and evolving disease entity. A 25-yr-old woman was
      admitted the clinic due to craniopharyngioma. After an extensive tumor resection,
      she complained of sustained fever, papillary contraction, hiccup, lacrimation,
      and sighing. An extensive evaluation of the sustained fever was conducted.
      Finally, the cause for MAHD was suspected, and the patient was successfully
      treated with bromocriptine for a month.

PMID- 22876069
TI  - Clinical factors associated with hepatitis A virus seropositivity in HIV-infected
      adults living in a country with an epidemiologic shift for hepatitis A virus
      infection.
AB  - The number of HIV-infected individuals susceptible to Hepatitis A virus (HAV)
      infection is increasing in Korea; however, it has proven difficult to devise a
      vaccination policy therefore because limited seroepidemiologic data exists for
      them. Accordingly, anti-HAV IgG was measured in 188 HIV-infected adults between
      July 2008 and July 2010. The nadir CD4+ T lymphocyte counts were not different
      between the HAV-positive and -negative groups (197 +/- 138 vs 202 +/- 129, P =
      0.821). The only factor independently associated with seropositive status was age
      under 40 yr old (OR 0.017, P < 0.001). Our findings suggest that HAV vaccination
      in HIV-infected adults should be targeted at persons under the age of 40 yr.

PMID- 22876070
TI  - Treatment of idiopathic clubfoot by ponseti technique of manipulation and serial
      plaster casting and its critical evaluation.
AB  - BACKGROUND: Clubfoot has from long been an unsolved clinical challenge for the
      orthopedic surgeons. It is one of the commonest congenital deformities in
      children. More than 100,000 babies are born worldwide each year with congenital
      clubfoot. Around 80% of the cases occur in developing nations. METHODS: Fifty
      three feet [mean Pirani score (total) 5.6] in 40 children were treated by the
      Ponseti method from June 2006 to December 2010. A prospective follow-up for a
      mean duration of 19.5 months (range 6-30 months) was undertaken. Evaluation of
      the deformity by Pirani score and goniometry was performed, before and after the
      treatment and the results were assessed through Wilcoxon signed rank test.
      RESULTS: The average number of casts applied before full correction was 4.9. The
      duration of casts for more than 85% feet was <7 weeks. 94.3% patients needed
      tenotomy before full correction. There was a significant difference in the pre
      treatment and the post-treatment Pirani score and goniometry values. CONCLUSION:
      Ponseti method of manipulation and plaster casting is very effective in
      correcting clubfoot deformity. It is especially important in developing countries
      and well-trained physicians and health personnel can manage the cases effectively
      by manipulation and cast application.

PMID- 22876071
TI  - Pelvic organ prolapse in jimma university specialized hospital, southwest
      ethiopia.
AB  - BACKGROUND: Pelvic organ prolapse is the down ward descent of female organs
      including the bladder, small and large bowel resulting in protrusion of the
      vagina, uterus or both. It is a disorder exclusive to women and one of the most
      common indications for gynecologic surgery. METHODS: This hospital based
      retrospective descriptive study was conducted to assess the magnitude of pelvic
      organ prolapse and risk factors for it. All cases of pelvic organ prolapse
      admitted and treated in Jimma University Specialized Hospital from July 1, 2008
      to June 30, 2011 were included. The collected data were analyzed using SPSS
      computer software version 16.0. Chi-square test was used and was considered to be
      significant when p<0.05. RESULTS: Pelvic organ prolapse accounted for 40.7% of
      major gynecologic operations. Mean age of patients was 42.43 +/- 10.4 years and
      there was a significant association between prolapse and age of patients (p
      <0.05). Mean parity of patients was 6.5+/- 2.64 with a significant association
      between prolapse and parity (p < 0.05). Majority of them (80.6%) lived in rural
      area and there was a significant association between prolapse and residence area.
      Farmers accounted for 68.2% of the patients and there was a significant
      association between prolapse and occupation (p < 0.05). Risk factors identified
      were chronic cough (20.9%), constipation (30.2%) with some having more than one
      risk factor while none was identified in 59.7%. CONCLUSION: Prolapse is common
      among rural, farmer, parous and older women where most of them delivered at home
      with prolonged labor. Age, parity and occupation were associated with the stage
      of prolapse. Awareness creation on risk factors of pelvic organ prolapse and use
      of contraception to reduce parity is recommended. Health institution delivery
      should be advocated to minimize the rate of home deliveries and hence of
      prolonged labor.

PMID- 22876072
TI  - Paracheck-pf(r) Test Versus Microscopy in the Diagnosis of Falciparum Malaria in
      Arbaminch Zuria Woreda of South Ethiopia.
AB  - BACKGROUND: Malaria is a major cause of morbidity and mortality in Ethiopia.
      Rapid diagnostic tests such as Paracheck Pf are the major tools for falciparum
      malaria diagnosis as an alternative to microscopy in peripheral health
      facilities. The objective of this study was to evaluate the sensitivity and
      specificity of Paracheck Pf against microscopy for diagnosis of P.falciparum
      infection and observe the persistence of the antigen for an elongated period.
      METHODS: Cross sectional study was undertaken in Arbaminch Zuria at Shele health
      center from October 2008 to January 2009. Paracheck-Pf versus microscopy
      comparison was done in conjunction with an artemisinin-based combination therapy
      efficacy monitoring for a period of 28 days. Standard microscopic procedures were
      done by experienced laboratory technicians and paracheck-Pf was performed in
      accordance with the manufacturer's instruction. RESULTS: out of 1293 examined
      blood films, 400(31%) were found to be malaria positive. Considering microscopy
      as the gold standard, paracheck-pf showed sensitivity of 94.1 %( 95%CI: 89.9
      98.3%) and specificity of 80.0% (95%CI: 67.6-92.4%). The positive and negative
      predictive values were 93.3 %( 95%CI: 88.8-97.8%) and 82.1% (95%CI: 70-94.1%),
      respectively. Comparing microscopy results 98.7 % (79/80), 60% (48/80), 48.1%
      (37/77), and 44.6 %( 33/74) were also found to be positive by paracheck-pf at
      days7, 14, 21, and 28, respectively. CONCLUSION: Paracheck Pf(r) has a comparable
      diagnostic performance in detecting P. falciparum infections through the
      persistence of frequent false positivity is a limitation. Thus, this diagnostic
      test is not appropriate for monitoring of treatment effect.

PMID- 22876073
TI  - Parents' perception, students' and teachers' attitude towards school sex
      education.
AB  - BACKGROUND: Sex education is described as education about human sexual anatomy,
      sexual reproduction, sexual intercourse, reproductive health, emotional
      relations, reproductive rights and responsibilities, abstinence, contraception,
      family planning, body image, sexual orientation, sexual pleasure, values,
      decision making, communication, dating, relationships, sexually transmitted
      infections (STIs) and how to avoid them, and birth control methods. This study
      was conducted to explore perception of parents about school sex education and
      assess the attitude of teachers and students towards school sex education.
      METHODS: A cross-sectional quantitative and qualitative study was conducted on
      randomly selected 386 students, total census of 94 teachers and 10 parents in
      Merawi Town from March 13-27, 2011. Data were collected using self-administered
      structured questionnaire and in-depth interview guideline. Multiple linear
      regression analysis was performed using total score to determine the effect of
      the independent variables on the outcome variable and thematic analysis was used
      to analyze the qualitative data. RESULTS: All study participants have favourable
      attitude towards the importance of school sex education. They also agreed that
      the content of school sex education should include abstinence-only and abstinence
      plus based on mental maturity of the students. That means at early age (Primary
      school) the content of school sex education should be abstinence-only and at
      later age (secondary school) the content of school sex education should be added
      abstinence-plus. The students and the teachers said that the minimum and maximum
      introduction time for school sex education is 5 year and 25 year with mean of
      10.97(SD+/-4.3) and 12.36(SD+/-3.7) respectively. Teacher teaching experiences
      and field of studies have supportive idea about the starting of school sex
      education. Watching romantic movies, reading romantic materials and listening
      romantic radio programs appear to have a contribution on the predictor of
      students' attitude towards the starting time of school sex education. CONCLUSION:
      All study participants have a need to start sex education at school. All study
      participants said that at early age (Primary school) the content of school sex
      education is abstinence-only and at later age (secondary school) is added
      abstinence-plus. School Sex education should be under considers the need of
      students, teachers and parents.

PMID- 22876074
TI  - Relationship between rewards and nurses' work motivation in addis ababa
      hospitals.
AB  - BACKGROUND: Nurses constitute the largest human resource element and have a great
      impact on quality of care and patient outcomes in health care organizations. The
      objective of this study was to examine the relationship between rewards and nurse
      motivation on public hospitals administrated by Addis Ababa health bureau.
      METHODS: A cross-sectional survey was conducted from June to December 2010 in 5
      public hospitals in Addis Ababa. Among 794 nurses, 259 were selected as sample.
      Data was collected using self-administered questionnaire. After the data was
      collected, it was analysed using SPSS version 16.0 statistical software. The
      results were analysed in terms of descriptive statistics followed by inferential
      statistics on the variables. RESULTS: A total of 230 questionnaires were returned
      from 259 questionnaires distributed to respondents. Results of the study revealed
      that nurses are not motivated and there is a statistical significant relationship
      between rewards and the nurse work motivation and a payment is the most important
      and more influential variable. Furthermore, there is significant difference in
      nurse work motivation based on age, educational qualification and work experience
      while there is no significant difference in nurse work motivation based on
      gender. CONCLUSION: The study shows that nurses are less motivated by rewards
      they received while rewards have significant and positive contribution for nurse
      motivation. Therefore, both hospital administrators' and Addis Ababa health
      bureau should revise the existing nurse motivation strategy.

PMID- 22876075
TI  - Comparative influence of self-efficacy, social support and perceived barriers on
      low physical activity development in patients with type 2 diabetes, hypertension
      or stroke.
AB  - BACKGROUND: Type 2 Diabetes, hypertension and stroke are strongly linked, and
      patients with any of these disorders are usually advised to be physically active
      based on existing evidence. However, different psychosocial constructs are found
      in separate settings to influence the physical activity levels of these different
      groups of patients. Hence, there is a need to establish the most important of the
      constructs to influence low physical activity in these groups of patients from
      Nigeria. METHODS: This cross-sectional study included 509 participants aged 35-80
      years from randomly selected health facilities in South-western Nigeria. Physical
      activity level, self-efficacy, social support and perceived barriers of the
      participants were assessed using the International Physical Activity
      Questionnaire, Exercise Self-Efficacy Scale, Medical Outcomes Social Support
      Scale and Exercise Benefits and Barrier Scale, respectively. RESULTS: The odds of
      having low physical activity was highest in those with low social support for
      Type 2 Diabetes (OR=3.95, 95% CI=3.13-5.24), stroke (OR=2.72, 95% CI=1.98-3.91)
      and mixed disorders (OR=1.59, 95% CI=1.19-3.15) while high perceived barriers was
      associated with the highest odds (OR=1.79, 95% CI=1.23-2.87) for low physical
      activity in hypertensive participants. CONCLUSIONS: Low social support had the
      highest influence in establishing low physical activity in patients with Type 2
      Diabetes, stroke and those with mixed disorders and the amount of influence was
      highest in those with Type 2 Diabetes. Psychosocial constructs should be
      considered by giving priority to social support when prescribing physical
      activity especially for patients with Type 2 Diabetes, stroke and those with
      mixed disorders.

PMID- 22876076
TI  - Urinary bacterial profile and antibiotic susceptibility pattern among pregnant
      women in north west ethiopia.
AB  - BACKGROUND: Urinary tract infection in pregnancy is associated with significant
      morbidity for both the mother and the baby. The aim of this study was to
      determine the bacterial profile and antibiotic resistance pattern of the urinary
      pathogens isolated from pregnant women at Felege Hiwot Referral Hospital
      Bahirdar, Ethiopia. METHODS: A total of 367 pregnant women with and without
      symptoms of urinary tract infection were enrolled as a study subject from October
      2010 to January 2011. Organisms were identified from mid-stream clean catch urine
      samples and antibiotic susceptibility was performed using bacteriological
      standard tests. Data were collected using structured questionnaires and were
      processed and analyzed using SPSS for Windows version 16. RESULTS: Out of 367
      pregnant women, 37 were symptomatic and the rest 330 asymptomatic.
      Bacteriological screening of urine samples revealed growth of bacteria in 8.5%
      (7/37) and 18.9% (28/330) for symptomatic and asymptomatic pregnant women
      respectively with overall prevalence of 9.5%. The most common isolates detected
      were E.coli (45.7%) followed by coagulase negative Staphylococcus (17.1%) and
      S.aureus (8.6%). Gram-negative bacteria showed resistance rates in the range of
      56.5% -82.6 % against trimethoprim/sulfamethoxazole, tetracycline, amoxicillin &
      ampicillin. Gram positive isolates showed resistant rate ranging from 50-100%
      against tetracycline, trimethoprim-sulphamethoxazole, amoxicillin and penicillin
      G. Both Gram positive and gram negative bacteria showed high sensitivity against
      Nitrofurantoin with a rate of 82.3% and 87%, respectively. All isolated Gram
      positive bacterial uropathogens were sensitive for Amoxicillin-clauvlanic acid.
      CONCLUSIONS: The isolation of bacterial pathogens both from symptomatic and
      asymptomatic pregnant women that are resistance to the commonly prescribed drug
      calls for an early screening of all pregnant women to urinary tract infection.

PMID- 22876077
TI  - Screening of primary school children for refractive error in South-South Nigeria.
AB  - BACKGROUND: Vision screening study in primary school children has not been done
      in Bayelsa State, South-South Nigeria. This study was therefore conducted to
      screen primary school children for refractive error in Bayelsa State and use the
      data to plan for an effective school Eye Health Program. METHODS: A cross
      sectional study on screening for refractive error in school children was carried
      out in Yenagoa Local Government Area of Bayelsa State in June 2009. A multistage
      sampling technique was used to select the study population (pupils aged 5-15
      years). Visual acuity for each eye was assessed by an Ophthalmic nurse and
      Optometrist outside the classroom, at 6 meters distance. Those with visual acuity
      of 6/9 or less were presented with a pinhole and the test repeated. Improvement
      of visual acuity with pinhole was considered refractive error. Funduscopy was
      done inside a poorly lit classroom. Data was analyzed with EPI INFO version 6.
      RESULTS: A total of 1,242 (658 females and 584 males) Pupils were examined. About
      97.7% of eyes had normal vision of 6/6 while 49 out of 56 eyes, with visual
      acuity of 6/9 or less, improved with pinhole. Twenty seven pupils had refractive
      error, giving a prevalence of 2.2%. Refractive error involved both eyes in 22
      pupils (81.5%) with the 8-10 years age range having the highest proportion
      (40.7%) of cases followed by 11-13 years age range (37.0%). CONCLUSION: The
      prevalence of refractive error in school children in Bayelsa State, South-South
      Nigeria was low.

PMID- 22876079
TI  - Do we know and apply the principles of academic authorship?

PMID- 22876078
TI  - A situational analysis of antimicrobial drug resistance in Africa: are we losing
      the battle?
AB  - BACKGROUND: The first arrival of a sizable shipment of penicillin at the North
      African Theatre of Operations for USA military use in 1943 was a landmark that
      turned a new chapter of antibiotic use in Africa. Over the past decade the
      expansion of resources and the technological advances have meant that much larger
      quantities of drugs are available in developing countries than ever before. As a
      result, many more individuals are receiving necessary treatment or therapy than
      just ten years ago. This very welcome event is accompanied by the terrible irony
      that increases in drug availability and use can promote drug resistance and
      render the same life-saving drugs ineffective. METHODS: The study focused on
      bacterial pathogens. One hundred and three relevant literatures were identified
      from the PubMed online database. The coverage included research articles
      concerning antimicrobial resistance involving subjects of an African country.
      RESULTS: Resistant bacteria are on a war path and evidently have acquired an edge
      over us. Our actions are evidently fuelling the resistance. The indiscriminate
      use of antibiotics in humans and livestock, wrong and substandard prescriptions
      by unqualified 'medical personnel' together with poor diagnosis or lack of it are
      all adding fuel to the already fired train of resistant microbes. CONCLUSION: To
      win the war and turn tables as we did with the discovery of penicillin and other
      antimicrobials in the 1940s, then we must all act now. Antimicrobial stewardship
      programs-Education, training of laboratory personnel and investment in laboratory
      infrastructure development are desirable in these situations.

PMID- 22876080
TI  - Development of 2D Microdisplay Using an Integrated Microresonating Waveguide
      Scanning System.
AB  - Our research team has developed a 2D micro image display device that can
      potentially overcome the size reduction limits while maintaining the high-image
      resolution and field of view obtained by mirror-based display systems. The basic
      design of the optical scanner includes a microfabricated SU-8 cantilever
      waveguide that is electromechanically deflected by a piezoelectric actuator. From
      the distal tip of the cantilever waveguide, a light beam is emitted and the
      direction of propagation is displaced along two orthogonal directions. The
      waveforms for the actuator and the LED light modulation are generated and
      controlled using a field programmable gate array. Our recent study is an update
      to the previously-reported mechanical scanner, replacing the hand-built PZT
      scanner and fiber waveguide with a microfabricated system incorporating aerosol
      deposited PZT thin film and a polymeric SU-8 wave guide. In this article, we
      report on the design and fabrication of a prototype miniaturized 2D scanner,
      discuss optical and mechanical the modeling of the system's properties and
      present the experimental results.

PMID- 22876081
TI  - Managing visits from pharmaceutical sales representatives.

PMID- 22876082
TI  - Bar-code rule for medical devices may be imminent.

PMID- 22876083
TI  - New drugs/drug news.

PMID- 22876084
TI  - Pharmaceutical approval update.

PMID- 22876085
TI  - Fidaxomicin (Dificid), a Novel Oral Macrocyclic Antibacterial Agent For the
      Treatment of Clostridium difficile-Associated Diarrhea in Adults.

PMID- 22876086
TI  - Evaluation of an adult insulin infusion protocol at an academic medical center.
AB  - OBJECTIVE: Acknowledging evidence of possible detrimental effects of tightly
      controlled blood glucose levels, the American Association of Clinical
      Endocrinologists and the American Diabetes Association published a consensus
      statement recommending less strict control for most diabetic patients. As a
      result of these recommendations, our academic center at Creighton University
      Medical Center revised its adult insulin infusion protocol to target blood
      glucose levels ranging from 120 to 180 mg/dL for regular (standard) glycemic
      control and 80 to 120 mg/dL for tight control; previous targets had ranged from
      80 to 180 mg/dL and 70 to 110 mg/dL, respectively. The primary objective was to
      evaluate the time that blood glucose values were within the target range for
      patients receiving the new protocol, compared with patients receiving the
      previous protocol. METHODS: Our study was designed to evaluate the effectiveness
      and safety of the revised protocol. Using a retrospective chart review, we
      collected data for 4 months from patients on the old insulin protocol (May to
      August 2009) and for 4 months from patients on the new protocol (September to
      December 2009). Secondary endpoints included the number of hypoglycemic episodes
      (blood glucose below 70 mg/dL) and severe hypoglycemic episodes (blood glucose 40
      mg/dL or lower) experienced by patients receiving the new insulin protocol
      compared with those receiving the former protocol. RESULTS: Patient
      characteristics were similar at baseline. Blood glucose values stayed within the
      target range for a significantly shorter time with the new protocol than with the
      former protocol (44.6% vs. 56.8%, respectively; P < 0.001), probably because of
      the narrower target range in the revised protocol. No statistically significant
      differences in hypoglycemia were observed after the protocol was changed.
      Hypoglycemia occurred in 31% of the former-protocol patients compared with 18% of
      the revised-protocol patients. Severe hypoglycemia was experienced by 2.1% of
      patients on the old protocol and by 3.1% of patients on the new protocol. Rates
      of severe hypoglycemia were low (2.6%) with the original protocol. CONCLUSION:
      Patients' blood glucose levels were within the target range for a shorter time
      with the new protocol. Fewer episodes of hypoglycemia were recorded with the new
      protocol, but rates of severe hypoglycemia were similar with both protocols.

PMID- 22876087
TI  - Drug use evaluation of moxifloxacin (avelox) using a hand-held electronic device
      at a canadian teaching hospital.
AB  - BACKGROUND: The use of moxifloxacin (Avelox) has increased at Vancouver General
      Hospital since its introduction onto the formulary in 2002. It is unclear,
      however, whether the use of the drug is optimal according to its indication. Hand
      held electronic devices, such as personal digital assistants (PDAs), are novel
      tools that can be used during routine patient care to collect data for drug use
      evaluation (DUE) reviews. OBJECTIVE: We hypothesized that moxifloxacin was over
      utilized and that opportunities existed to optimize its use. This study was
      designed to characterize moxifloxacin use in concordance with evidence-based
      assessment criteria. The feasibility of using a PDA device as a data-collection
      tool was also evaluated. DESIGN: An observational DUE was conducted over a 4-week
      period (from February 17 to March 16, 2007) at Vancouver General Hospital, a 955
      bed tertiary care hospital. Inpatients who received at least one dose of
      moxifloxacin were enrolled. Evidence-based assessment criteria were developed to
      evaluate the appropriateness of moxifloxacin use, and a PDA database was
      developed for data collection. The primary endpoint was the proportion of
      moxifloxacin use for approved first-line indications. RESULTS: A total of 132
      patients were included. Eighty-nine patients (67%) received moxifloxacin for
      first-line indications, including community-acquired pneumonia (57%) and acute
      exacerbation of chronic bronchitis (10%). Forty-three patients (33%) had
      alternative indications, primarily hospital-acquired pneumonia (25%). In 129
      evaluable patients, approximately half (51%) of the clinical outcomes were
      successful; 37% were indeterminate; and 12% were failures. General medicine and
      respiratory service clinicians prescribed moxifloxacin more appropriately
      compared with surgical service personnel. Most of the pharmacists supported the
      use of PDAs as DUE data-collection tools. CONCLUSION: Overall, moxifloxacin
      utilization at Vancouver General Hospital was appropriate according to evidence
      based assessment criteria. Additional opportunities to improve its use exist
      through health care staff education. PDAs are ideal data-collection tools for
      DUEs, as they can be conveniently used during routine patient care.

PMID- 22876088
TI  - FDA Considers a New Paradigm For Over-the-Counter Medications: More Power-but
      More Burdens-for Pharmacists and Pharmacies.

PMID- 22876089
TI  - 2012 american college of cardiology, 61st annual scientific session & expo.

PMID- 22876090
TI  - Actively caring for the safety of patients: overcoming bystander apathy.

PMID- 22876091
TI  - FDA to reassess policies on unsolicited requests for off-label information:
      differentiating 'scientific exchange' from 'promotion' is complicated.

PMID- 22876093
TI  - Pharmaceutical approval update.

PMID- 22876092
TI  - New drugs/drug news.

PMID- 22876094
TI  - Part d changes for 2013 will put pressure on p&t committees: drug utilization
      reviews and medication therapy management programs under the gun.

PMID- 22876095
TI  - Policies and procedures: enhancing pharmacy practice and limiting risk.

PMID- 22876097
TI  - 47th European Association for the Study of the Liver (EASL)/The International
      Liver Conference.

PMID- 22876098
TI  - American academy of dermatology.

PMID- 22876099
TI  - Physical environments that promote safe medication use.
AB  - The physical design of an organization's workspace can enhance or diminish
      patient safety.

PMID- 22876101
TI  - New drugs/drug news.

PMID- 22876100
TI  - FDA's new authority on drug shortages.
AB  - Drug companies may be required to report shortages sooner, but the FDA
      legislation still lacks power.

PMID- 22876102
TI  - Pharmaceutical approval update.
AB  - Tazarotene (Fabior Foam) for acne; estradiol valerate and estradiol
      valerate/dienogest (Natazia) for heavy menstrual bleeding; and taliglucerase alfa
      (Elelyso) for Gaucher's disease.

PMID- 22876103
TI  - Fospropofol disodium (lusedra) injection for anesthesia-care sedation: a clinical
      review.
AB  - Fospropofol disodium (Lusedra) for anesthesia sedation.

PMID- 22876096
TI  - Management of urinary incontinence.

PMID- 22876104
TI  - Hydrocodone rescheduling amendment and pipeline products on the horizon.
AB  - A controversial bill to change the classification of the opioid hydrocodone from
      Schedule II to Schedule II might help decrease the incidence of drug abuse
      through stricter regulation of Schedule II products, or, as some groups claim, it
      might hinder access for patients with legitimate prescriptions.

PMID- 22876105
TI  - Therapy for stable angina in women.
AB  - Mortality rates for cardiovascular disease are higher in women than in men, but
      studies of women have been conducted less frequently. Current pharmacological and
      nonpharmacological treatment options for women with stable angina are reviewed.

PMID- 22876106
TI  - Hydroxyprogesterone caproate injection (makena) one year later: to compound or
      not to compound that is the question.
AB  - Preterm births have increased by 27% over the last decade in the U.S. The main
      ingredient in Makena, 17P, is less expensive at compounding pharmacies, but this
      method is not FDA-approved. The authors discuss the quality, safety, and use of
      Makena and compounded 17P; the potential for liability; cost considerations; and
      recommended restrictions for the product's use.

PMID- 22876107
TI  - A review of abuse-deterrent opioids for chronic nonmalignant pain.
AB  - Chronic nonmalignant pain, which affects millions of people, is the most common
      reason patients seek medical care. Both current and potential opioid analgesics
      are discussed, along with new technologies used to prevent abuse.

PMID- 22876108
TI  - Parenting Young Children (PARYC): Validation of a Self-Report Parenting Measure.
AB  - The measurement of parenting behaviors is important to the field of psychology
      and the goal of remediating problematic parenting as a means of reducing child
      problem behaviors. The Parenting Young Children (PARYC) is a self-report measure
      designed to address parenting behaviors relevant for the caregivers of young
      children, and was assessed in sample of 579 high risk families. The measure
      assesses the frequency of several parenting behaviors, the perception of the
      parenting behaviors as problematic, and the degree to which the caregiver would
      like to make changes in specific parenting skills. An examination of the validity
      of the parenting behavior items revealed three parenting scales: (1) Supporting
      Positive Behavior (2) Setting Limits, and (3) Proactive Parenting. Confirmatory
      factor analysis results corroborate the findings of the exploratory factor
      analysis, supporting the measurement structure of these parenting scales. Tests
      of convergent validity indicate the PARYC scale is a suitable measure of
      parenting behaviors. In addition, the self-perception of parenting behaviors as
      problematic predicted concurrent levels of service utilization while controlling
      for simultaneous child behavior problems.

PMID- 22876109
TI  - Molecular approach in the study of Alstrom syndrome: analysis of ten Spanish
      families.
AB  - PURPOSE: To describe the clinical and genetic findings in 11 Spanish patients
      with confirmed (n=5) or suspected (n=6) Alstrom syndrome (AS). METHODS: Patients
      underwent clinical evaluation, and were screened for variations in Alstrom
      syndrome 1 gene (ALMS1) using a genotyping microarray from Asper Ophthalmics and
      by direct sequencing of coding exons 8, 10, and 16 of ALMS1. Furthermore, we
      analyzed the presence of the A229T variant of retinitis pigmentosa GTPase
      regulator-interacting protein 1-like gene (RPGRIP1L) with direct sequencing of
      coding exon 6. RESULTS: A great phenotypic variability was observed in our
      patients. Four mutations in ALMS1-two novel nonsense mutations in one family
      (p.Y1715X and p.S616X), one previously described mutation in homozygous state in
      another family (p.V3597Efs*4), and a likely pathogenic missense variation
      p.P1822L in a third family-were identified with direct sequencing. All patients
      were homozygous for 229A allele of RPGRIP1L, with the exception of a p.A229T
      heterozygous patient. CONCLUSIONS: Our findings expand the spectrum of ALMS1
      mutations causing Alstrom syndrome. The phenotypic differences between patients
      could be attributed to interactions with other genes inherited independently from
      the ALMS1 gene or with environmental factors. A clear understanding of the
      phenotypic spectrum in AS will be important to unravel the molecular mechanisms
      underlying this syndrome.

PMID- 22876110
TI  - Complement factor H and interleukin gene polymorphisms in patients with non
      infectious intermediate and posterior uveitis.
AB  - OBJECTIVE: To investigate the associations of complement factor H (CFH),
      KIAA1109, and interleukin-27 (IL-27) gene polymorphisms in patients with non
      infectious intermediate and posterior uveitis. METHODS: The study cohort
      consisted of a total of 95 Chinese non-infectious uveitis patients, including 38
      patients with intermediate uveitis (IU), 38 patients with Vogt-Koyanagi-Harada
      disease (VKH), and 19 patients with Behcet's disease and 308 healthy controls.
      The genotypes of CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were
      determined using TaqMan single nucleotide polymorphism genotyping assays.
      RESULTS: The frequency of carriers of G allele for CFH-rs800292 was significantly
      higher in patients with non-infectious intermediate and posterior uveitis than in
      controls (GG/AG versus AA; p=0.02). No significant association was found between
      uveitis and both KIAA1109-rs4505848 and IL27-rs4788084. In stratified analysis by
      gender, the frequency of carriers with G allele for KIAA1109-rs4505848 was
      significantly higher in male uveitis patients than in male controls (GG/AG versus
      AA; p=0.034). There was no significant difference in allelic and genotypic
      frequencies for CFH-rs800292 and IL27-rs4788084 in either male or female groups.
      In addition, higher frequency of KIAA1109-rs4505848 G allele was found in
      Behcet's disease patients compared with controls and IU patients (p=0.01 and
      p=0.003, respectively). CONCLUSIONS: Our results demonstrated that CFH-rs800292
      and KIAA1109-rs4505848 are associated with non-infectious intermediate and
      posterior uveitis. Moreover, gender susceptibility for uveitis might be involved
      in the KIAA1109 gene and the KIAA1109-rs4505848 polymorphism might be associated
      with the development of Behcet's disease.

PMID- 22876111
TI  - A nonsense mutation of CRYGC associated with autosomal dominant congenital
      nuclear cataracts and microcornea in a Chinese pedigree.
AB  - PURPOSE: To report the identification of a nonsense mutation in gammaC-crystallin
      (CRYGC) associated with autosomal dominant congenital nuclear cataracts and
      microcornea in a Chinese family. METHODS: We investigated four generations of a
      Chinese family six of whose members were affected by nuclear cataracts and
      microcornea. The genomic DNA was extracted from peripheral blood leukocytes. All
      reported nuclear cataract-related candidate genes were screened for causative
      mutations by direct DNA sequencing. The effects of amino acid changes on the
      structure and function of proteins were predicted by bioinformatics analysis.
      RESULTS: All affected individuals in this family exhibited nuclear cataracts and
      microcornea. Direct sequencing of the candidate gene cluster showed a c.471G>A
      transition in exon 3 of CRYGC, which co-segregated according to family members
      with cataracts, and was not observed in 100 normal controls. This single
      nucleotide change was predicted to introduce a translation stop codon at
      tryptophan 157 (W157X). Bioinformatics analysis showed that the mutation was
      predicted to affect the function and secondary structure of the CRYGC protein.
      CONCLUSIONS: This study identified a disease-causing mutation c.471G>A in CRYGC
      in a Chinese family with cataracts, expanding the mutation spectrum of CRYGC
      causing congenital cataracts.

PMID- 22876112
TI  - Smad7 siRNA inhibit expression of extracellular matrix in trabecular meshwork
      cells treated with TGF-beta2.
AB  - PURPOSE: Extracellular matrix (ECM) deposits lead to elevated resistance of
      aqueous humor outflow which play an important role in the development of primary
      open angle glaucoma (POAG). The TGF-beta2 (transforming growth factor beta)/Smad
      (signaling mathers against decapentaplegic) pathway is known to regulate the ECM
      deposits. In this study, we determined the effect of Smad7 siRNA transfection in
      inhibiting the expression of ECM components. METHODS: Plasmid containing Smad7
      siRNA was used to transfect cultured human trabecular meshwork cells (HTM).
      Protein expression of Smad7, fibronectin, and laminin was determined using
      western blot. RESULTS: Downregulation of Smad7 interrupts the effects of TGF
      beta2 on the expression of several ECM components. Smad7 siRNA can partially
      decrease the expression of Smad7, fibronectin, and laminin. CONCLUSIONS: Smad7
      plays an important role in regulating the ECM protein in the aqueous outflow
      pathway.

PMID- 22876113
TI  - USH1G with unique retinal findings caused by a novel truncating mutation
      identified by genome-wide linkage analysis.
AB  - PURPOSE: Usher syndrome (USH) is an autosomal recessive disorder divided into
      three distinct clinical subtypes based on the severity of the hearing loss,
      manifestation of vestibular dysfunction, and the age of onset of retinitis
      pigmentosa and visual symptoms. To date, mutations in seven different genes have
      been reported to cause USH type 1 (USH1), the most severe form. Patients
      diagnosed with USH1 are known to be ideal candidates to benefit from cochlear
      implantation. METHODS: Genome-wide linkage analysis using Affymetrix GeneChip
      Human Mapping 10K arrays were performed in three cochlear implanted Saudi
      siblings born from a consanguineous marriage, clinically diagnosed with USH1 by
      comprehensive clinical, audiological, and ophthalmological examinations. From the
      linkage results, the USH1G gene was screened for mutations by direct sequencing
      of the coding exons. RESULTS: We report the identification of a novel p.S243X
      truncating mutation in USH1G that segregated with the disease phenotype and was
      not present in 300 ethnically matched normal controls. We also report on the
      novel retinal findings and the outcome of cochlear implantation in the affected
      individuals. CONCLUSIONS: In addition to reporting a novel truncating mutation,
      this report expands the retinal phenotype in USH1G and presents the first report
      of successful cochlear implants in this disease.

PMID- 22876114
TI  - Caspase-14: a novel caspase in the retina with a potential role in diabetic
      retinopathy.
AB  - PURPOSE: The purpose of this study was to evaluate caspase-14 expression in the
      retina under normal and diabetic conditions, and to determine whether caspase-14
      contributes to retinal microvascular cell death under high glucose conditions.
      METHODS: Quantitative real-time polymerase chain reaction and western blot
      analysis were used to evaluate caspase-14 expression in retinal cells, including
      pericytes (PCs), endothelial cells (ECs), astrocytes (ACs), choroidal ECs, and
      retinal pigment epithelium (RPE) cells. We also determined caspase-14 expression
      in the retinas of human subjects with or without diabetic retinopathy (DR) and in
      experimental diabetic mice. Retinal ECs and PCs were infected with adenoviruses
      expressing human caspase-14 or green fluorescent protein. Caspase-14 expression
      was also assessed in retinal vascular cells cultured under high glucose
      conditions. The number of apoptotic cells was determined with terminal
      deoxynucleotidyl transferase dUTP nick end labeling staining and confirmed by
      determining the levels of cleaved poly (ADP-ribose) polymerase-1 and caspase-3.
      RESULTS: Our experiments demonstrated that retinal ECs, PCs, ACs, choroidal ECs,
      and RPE cells expressed caspase-14, and DR was associated with upregulation
      and/or activation of caspase-14 particularly in retinal vasculature. High glucose
      induced marked elevation of the caspase-14 level in retinal vascular cells. There
      was a significant increase in the apoptosis rate and the levels of cleaved poly
      (ADP-ribose) polymerase-1 and caspase-3 in retinal ECs and PCs overexpressing
      caspase-14. CONCLUSIONS: Our findings indicate that caspase-14 might play a
      significant role in the pathogenesis of DR by accelerating retinal PC and EC
      death. Further investigations are required to elaborate the underlying
      mechanisms.

PMID- 22876116
TI  - Identification of a novel FBN1 gene mutation in a large Pakistani family with
      Marfan syndrome.
AB  - PURPOSE: To describe a novel mutation in the fibrillin-1 (FBN1) gene in a large
      Pakistani family with autosomal dominant Marfan syndrome (MFS). METHODS: Blood
      samples were collected of 11 family members affected with Marfan syndrome, and
      DNA was isolated by phenol-extraction. The coding exons of FBN1 were analyzed by
      polymerase chain reaction (PCR) and direct sequencing. One hundred-thirty
      controls were screened for a mutation in the FBN1 gene that was identified in
      this family by restriction fragment length polymorphism (RFLP) analysis. RESULTS:
      A novel heterozygous missense mutation c.2368T>A; p.Cys790Ser was observed in
      exon 19. This mutation substitutes a highly conserved cysteine residue by serine
      in a calcium binding epidermal growth factor-like domain (cbEGF) of FBN1. This
      mutation was present in all affected members and absent from unaffected
      individuals of the family in addition to 130 healthy Pakistani controls.
      Interestingly all affected family members presented with ectopia lentis, myopia
      and glaucoma, but lacked the cardinal cardiovascular features of MFS.
      CONCLUSIONS: This is a first report of a mutation in FBN1 in MFS patients of
      Pakistani origin. The identification of a FBN1 mutation in this family confirms
      the diagnosis of MFS patients and expands the worldwide spectrum of FBN1
      mutations.

PMID- 22876115
TI  - A novel cytarabine crystalline lipid prodrug: hexadecyloxypropyl cytarabine 3',5'
      cyclic monophosphate for proliferative vitreoretinopathy.
AB  - PURPOSE: The objectives of this study were to synthesize and characterize two
      types of cytarabine (Ara-C) lipid produgs and evaluate the prodrugs for sustained
      intraocular delivery after administration by intravitreal injection. METHODS:
      Hexadecyloxypropyl cytarabine 5'-monophosphate (HDP-P-Ara-C) and
      hexadecyloxypropyl cytarabine 3',5'-cyclic monophosphate (HDP-cP-Ara-C) were
      synthesized starting from cytarabine (1-beta-D-arabinofuranosylcytosine). Their
      vitreal clearance profile was simulated using a custom dissolution chamber, in
      vitro cytotoxicity was evaluated using cell proliferation assays, and in vivo
      ocular properties in rat and rabbit eyes were assessed using biomicroscopy,
      indirect ophthalmoscopy, tonometry, electroretinography, and histology. RESULTS:
      HDP-P-Ara-C was cleared from the dissolution chamber (flow rate 2 uL/min) within
      7 days. In contrast, HDP-cP-Ara-C, a much more insoluble prodrug, was still
      detectable 36 days after the dissolution process was started. HDP-P-Ara-C had a
      50% cytotoxicity concentration of 52+/-2.6 MUM in human retinal pigment
      epithelium (ARPE-19) and 32+/-2.2 uM in a rat Muller cell line, rMC-1. The 50%
      cytotoxicity concentration values for HDP-cP-Ara-C in ARPE-19 and rMC-1 cells
      were 50 uM and 25 uM, respectively. HDP-P-Ara-C was not detectable 2 weeks after
      the highest intravitreal dose (228 ug/rat eye) was injected, and no ocular
      toxicity was found. With HDP-cP-Ara-C, the drug depot was visible for 26 weeks
      following a single intravitreal injection (800 ug/rabbit eye). For both
      compounds, the electroretinogram, intraocular pressure, and other toxicity
      studies were negative except for the highest dose of HDP-cP-Ara-C (800 ug/eye),
      which had focal toxicity from the direct touch of the retina and decreased dark
      adapted a-waves and decreased flicker electroretinogram amplitudes (generalized
      estimating equations, p=0.039 and 0.01). CONCLUSIONS: The cyclic monophosphate
      prodrug, HDP-cP-Ara-C, was found to have physiochemical properties better suited
      for sustained delivery of cytarabine to posterior segments of the eye. These
      properties included limited aqueous solubility, in vitro antiproliferative
      activity, and good tolerability after injection into rabbit eyes.

PMID- 22876117
TI  - Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 are strongly expressed in the
      epithelium of human granular and lattice type I corneal dystrophies.
AB  - PURPOSE: To determine the extracellular matrix proteins involved in the formation
      of human granular and lattice type I corneal stromal dystrophies, the expression
      patterns of fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were compared in
      human corneal stromal dystrophy samples. METHODS: Ten cases of granular
      dystrophy, 7 cases of lattice dystrophy, and 6 normal corneal buttons collected
      during corneal transplantation were examined for their expression patterns of
      fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 by immunohistochemistry.
      RESULTS: Highly elevated fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were
      observed in the epithelial layer of both granular and lattice type I dystrophies.
      Fibrillin-2, tenascin-C, and matrilin-4 in the granular dystrophy and all
      antibodies in the lattice dystrophy showed statistically significant staining in
      the corneal stroma (p<0.05). Interestingly, fibrillin-2, matrilin-2, and matrilin
      4 stained significantly in amyloid plaques of lattice type 1 dystrophy.
      CONCLUSIONS: Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 may be markers
      of the pathogenesis of either granular or lattice type I corneal dystrophy, as
      revealed by immunohistochemical analysis. Each molecule seems to be involved in
      the regeneration and reorganization of the corneal matrix in granular and lattice
      type I dystrophies.

PMID- 22876118
TI  - CYP1A1 protein activity is associated with allelic variation in pterygium tissues
      and cells.
AB  - BACKGROUND: A thymine/cytosine point mutation in the MSP I restriction site of
      cytochrome P450 1A1 (CYP1A1) has been linked to susceptibility to smoking-related
      cancers and is reported to result in increased enzyme activity. Therefore, we
      sought to determine whether allelic variation of CYP1A1 is associated with
      protein expression and protein activity in pterygium. METHODS: We collected 150
      pterygium samples and 50 normal conjunctiva samples, which served as controls.
      DNA samples were extracted from blood cells and then subjected to real-time
      ploymerase chain reaction (PCR) to determine CYP1A1 genotype. CYP1A1 protein
      expression was determined by immunohistochemical staining with a monoclonal
      antibody for CYP1A1. Pterygium epithelial cells (PECs), cultured in a serum-free
      culture medium, real-time PCR, western blot and enzyme-linked immunosorbent assay
      (ELISA) were used to understand the effect of CYP1A1 allelic variation in protein
      expression and activity. RESULTS: Forty-eight (33.3%) pterygium specimens tested
      positive for CYP1A1 protein expression. CYP1A1 protein expression was
      significantly greater in the pterygium group than in the control group
      (p<0.0001). In addition, CYP1A1 protein expression was associated with allelic
      variation. CYP1A1 protein expression was significantly greater in the m2/m2 group
      than in the m1/m1and m1/m2 groups (p=0.006). In the cell model, CYP1A1 protein
      expression and b[a]P 7,8-diol 9,10-epoxide (BPDE)-like DNA adducts increased in
      CYP1A1 m2/m2 (genotype T/T) PEC cells as compared with m1/m2 (genotype C/T) and
      m1/m1 (genotype C/C) cells. CONCLUSIONS: CYP1A1 expression in pterygium
      correlates with allelic variation and can be used as an independent risk marker.

PMID- 22876119
TI  - A novel MYOC heterozygous mutation identified in a Chinese Uygur pedigree with
      primary open-angle glaucoma.
AB  - PURPOSE: To characterize the clinical features of a Chinese Uygur pedigree with
      primary open-angle glaucoma (POAG) and to identify mutations in two candidate
      genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and
      human dioxin-inducible cytochrome P450 (CYP1B1). METHODS: Twenty one members from
      a Chinese Uygur family of four generations were included in the study. All
      participants underwent complete ophthalmologic examinations. Five were diagnosed
      as POAG, four as glaucoma suspects, and the rest were asymptomatic. Molecular
      genetic analysis was performed on all subjects included in the study. All exons
      of CYP1B1 and MYOC were amplified by polymerase chain reaction (PCR), sequenced
      and compared with a reference database. The variations detected were evaluated in
      available family members as well as 102 normal controls. Possible changes in
      structure and function of the protein induced by amino acid variance were
      predicted by bioinformatics analysis. RESULTS: Elevated intraocular pressure and
      late-stage glaucomatous cupping of the optic disc were found in five patients of
      this family. A novel heterozygous missense mutation c.1151 A>G in exon 3 of MYOC
      was found in all five patients diagnosed as POAG and four glaucoma suspects, but
      not in the rest of the family members and 102 normal controls. This mutation
      caused an amino acid substitution of aspartic acid to glycine at position 384 (p.
      D384G) of the MYOC protein. This substitution may cause structural and functional
      changes of the protein based on bioinformatics analysis. No mutations were found
      in CYP1B1. CONCLUSIONS: Our study suggests that the novel mutation D384G of MYOC
      is likely responsible for the pathogenesis of POAG in this pedigree.

PMID- 22876120
TI  - The tear film characteristics of spontaneous subconjunctival hemorrhage patients
      detected by Schirmer test I and tear interferometry.
AB  - PURPOSE: To evaluate the tear film characteristics of spontaneous subconjunctival
      hemorrhage patients by Schirmer test I and tear interferometry. METHODS: Forty
      six spontaneous subconjunctival hemorrhage patients and 46 controls were enrolled
      in the study. Schirmer test I and tear interferometry were performed in all 92
      subjects. The results obtained were compared between the two groups. RESULTS: The
      Schirmer test I value of the spontaneous subconjunctival hemorrhage patients was
      6.93 (4.72) mm, and that of the controls was 14.70 (3.70) mm. A statistical
      difference was found between the two groups (independent samples t test, t=-8.79,
      p<0.001). The mean rank of the tear interferometry patterns of the spontaneous
      subconjunctival hemorrhage patients was 50.07, and that of the controls was
      42.93. No statistical difference was found between the two groups (Mann-Whitney U
      test, Z=-1.85, p=0.064). CONCLUSIONS: For the spontaneous subconjunctival
      hemorrhage patients, the Schirmer test I value was lower than that of the
      controls, whereas the tear interferometry patterns were comparable to that of the
      controls.

PMID- 22876121
TI  - Mitochondrial genetic background in Ghanaian patients with primary open-angle
      glaucoma.
AB  - PURPOSE: Prevalence rates for primary open-angle glaucoma (POAG) are
      significantly higher in Africans than in European or Asians. It has been reported
      recently that mitochondrial DNA (mtDNA) lineages of African origin, excluding L2,
      conferred susceptibility to POAG in Saudi Arabia. This prompted us to test the
      role of mtDNA haplogroups in the incidence of POAG in the Ghanaian population who
      has a high frequency of L2 lineages. METHODS: DNA was extracted from two
      independent cohorts of clinically diagnosed POAG patients (n=373) and healthy
      controls (n=451). All patients and controls were from Accra and Tema (the
      southern region of Ghana). The hypervariable region-I (HVS-I) and coding regions
      comprising mtDNA haplogroup diagnostic polymorphisms were polymerase chain
      reaction (PCR) amplified and sequenced in all patients and controls and the
      haplotypes obtained were assorted into haplogroups and their frequencies compared
      between cohorts. RESULTS: No statistically significant differences were found in
      mtDNA haplogroup frequencies between POAG patients and matched controls in this
      cohort for the various mtDNA haplogroups tested. CONCLUSIONS: In this Ghanaian
      cohort, mtDNA haplogroups do not seem to confer susceptibility to POAG.

PMID- 22876122
TI  - Lack of association of SNP rs4236601 near CAV1 and CAV2 with POAG in a Saudi
      cohort.
AB  - PURPOSE: To determine the role of the recently discovered primary open angle
      glaucoma (POAG) single nucleotide polymorphism (SNP) rs4236601 near the caveolin
      1 (CAV1) and CAV2 among patients and controls from Saudi Arabia. METHODS: A
      cohort of 220 POAG patients and 405 control subjects from Saudi Arabia were
      genotyped for a SNP (rs4236601;g.2891 G>A) in the chromosome 7q31 locus near CAV1
      and CAV2 using a standard polymerase chain reaction (PCR) and sequencing method.
      RESULTS: The minor allele frequency (MAF) of rs4236601 was 0.3 in controls and
      0.31 in POAG patients. We detected no statistical difference when we compared the
      allele frequencies between POAG patients and control subjects (p=0.699).
      Similarly, we detected no statistical difference in the frequency of the three
      possible rs4236601 genotypes between patients and controls. The p-values were
      0.928 and 0.683 for heterozygous genotype (G/A) and homozygous mutant genotype
      (A/A), respectively. We found no statistically significant difference among
      patients with any of the three possible genotypes and various clinical indices
      important for glaucoma. Among patients with homozygous (A/A), the mean IOP was
      higher (21.4) compared to patients with G/G wildtype (20.4) and to patients with
      G/A genotype (18.5). However, this apparent difference did not reach the
      statistical significance threshold (p=0.062). CONCLUSIONS: We were unable to
      detect this association in our POAG-patients from Saudi Arabia, suggesting that
      this risk factor may not have a strong effect in all populations. A founder
      effect may play a role in certain populations where the link was established.

PMID- 22876123
TI  - Curcumin suppresses ovalbumin-induced allergic conjunctivitis.
AB  - PURPOSE: Allergic conjunctivitis (AC) from an allergen-driven T helper 2 (Th2)
      response is characterized by conjunctival eosinophilic infiltration. Because
      curcumin has shown anti-allergic activity in an asthma and contact dermatitis
      laboratory models, we examined whether administration of curcumin could affect
      the severity of AC and modify the immune response to ovalbumin (OVA) allergen in
      an experimental AC model. METHODS: Mice were challenged with two doses of topical
      OVA via the conjunctival sac after systemic sensitization with OVA in aluminum
      hydroxide (ALUM). Curcumin was administered 1 h before OVA challenge. Several
      indicators for allergy such as serum immunoglubulin E (IgE) antibodies
      production, eosinophil infiltration into the conjunctiva and Th2 cytokine
      production were evaluated in mice with or without curcumin treatment. RESULTS:
      Mice challenged with OVA via the conjunctival sac following systemic
      sensitization with OVA in ALUM had severe AC. Curcumin administration markedly
      suppressed IgE-mediated and eosinophil-dependent conjunctival inflammation. In
      addition, mice administered curcumin had less interleukin-4 (IL-4) and
      interleukin-5 (IL-5) (Th2 type cytokine) production in conjunctiva, spleen, and
      cervical lymph nodes than mice in the non-curcumin-administered group. OVA
      challenge resulted in activation of the production of inducible nitric oxide
      (iNOS), and curcumin treatment inhibited iNOS production in the conjunctiva.
      CONCLUSIONS: We believe our findings are the first to demonstrate that curcumin
      treatment suppresses allergic conjunctival inflammation in an experimental AC
      model.

PMID- 22876124
TI  - Synthesis of thiolated chitosan and preparation nanoparticles with sodium
      alginate for ocular drug delivery.
AB  - PURPOSE: The goal of the present study was to synthesize mucoadhesive polymer -
      thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate
      nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular
      drug delivery. METHODS: A new method for preparing TCS was developed, and the
      characteristics were determined using Fourier transform infrared spectroscopy and
      the degree of thiol immobilized was measured by Ellman's reagent. Human corneal
      epithelium (HCE) cells were incubated with different concentrations of TCS for 48
      h to determine the cell viabilities. CS/TCS-SA NPs were prepared and optimized by
      a modified ionic gelation method. The particle sizes, zeta potentials, Scanning
      electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo
      studies of the two types of NP were compared. RESULTS: The new method enabled a
      high degree of thiol substitution of TCS, up to 1,411.01+/-4.02 MUmol/g. In vitro
      cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs,
      TCS-SA NPs were more stable, with higher mucoadhesive properties and could
      deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo.
      CONCLUSIONS: TCS-SA NPs have better delivery capability, suggesting they have
      good potential for ocular drug delivery applications.

PMID- 22876125
TI  - Wnt3a promotes epithelial-mesenchymal transition, migration, and proliferation of
      lens epithelial cells.
AB  - PURPOSE: Posterior capsular opacification (PCO) is caused mainly by the
      epithelial-mesenchymal transition (EMT), proliferation, and migration of human
      lens epithelial (HLE) cells. wingless (Wnt) signaling has been implicated in the
      fibrotic process by inducing EMT and increasing the proliferation of epithelial
      cells. This study investigated the role of Wnt3a in PCO formation. METHODS: Wnt3a
      was overexpressed in the HLE B-3 cell line by transfected Wnt3a-pcDNA3 plasmid.
      The expressions of Wnt/beta-catenin signaling component proteins, including beta
      catenin, E-cadherin, fibronectin, c-Myc, and cyclin D1, were detected by western
      blot analysis and immunocytofluorescence to confirm the efficiency of
      transfection efficiency and analyze the effects of overexpression. HLE migration
      ability was evaluated by transwell migration and wound healing assays, whereas
      HLE proliferation was analyzed by MTT [3-(4,5-dimethylthiazol-2-yl) -2,5
      diphenyltetrazolium bromide] assay and flow cytometry. RESULTS: Overexpression of
      Wnt3a resulted in upregulated expression of beta-catenin, c-Myc, and cyclin D1.
      Expression of the lens epithelial marker E-cadherin was down-regulated in Wnt3a
      overexpressing HLE B-3 cells, whereas that of the mesenchymal marker fibronectin
      was upregulated. In addition, the morphology of HLE B-3 cells changed from the
      classic spindle shape to an irregular form. Overexpression of Wnt3a could enhance
      the ability of migration as determined by transwell migration and wound healing
      assays as well as promoted the proliferation of HLE B-3 cells by MTT assay and
      flow cytometry analysis. CONCLUSIONS: Wnt3a can induce EMT, migration, and
      proliferation of HLE cells and may be a valuable therapeutic target for the
      prevention and treatment of PCO.

PMID- 22876126
TI  - Erythropoietin levels in aqueous humor of patients with glaucoma.
AB  - PURPOSE: To compare the aqueous concentration of erythropoietin (EPO) in eyes
      with primary open-angle (POAG), pseudoexfoliative (PXFG), and neovascular (NVG)
      glaucoma with age-matched eyes with cataracts, and to correlate its concentration
      with other factors including age, gender, intraocular pressure (IOP), type of
      glaucoma, and severity of glaucoma. METHODS: In this prospective non-randomized
      comparative study, a total of 26 eyes with cataracts (control group) and 92
      glaucomatous eyes (POAG, 40 eyes; PXFG, 26 eyes; NVG, 26 eyes) were enrolled.
      Aqueous samples (0.1 to 0.2 ml) were obtained during phacoemulsification,
      trabeculectomy, phacotrabeculectomy, or Ahmed valve glaucoma implants. The
      aqueous concentration of EPO was measured using an enzyme-linked immunosorbent
      assay. RESULTS: The mean+/-SEM aqueous level of EPO was statistically
      significantly higher in eyes with glaucoma (56.7+/-9.3 mIU/ml) compared to the
      control group (0.8+/-0.51 mIU/ml; p<0.001). Eyes with NVG had the highest aqueous
      level of EPO. Aqueous EPO concentrations remained considerably elevated even in
      eyes with controlled IOP in all three types of glaucoma. Eyes with PXFG displayed
      the greatest change in aqueous EPO concentration proportionate to the IOP level.
      In simple regression analysis, IOP, mean deviation, and the type of glaucoma were
      the factors that had a statistically significantly positive correlation with the
      aqueous level of EPO (p=0.011 and <0.001, respectively). Only the type of
      glaucoma remained statistically significant in the multiple regression analysis
      (adjusted R(2)=0.278). CONCLUSIONS: Compared to the control group, the aqueous
      humor EPO concentration is increased in eyes with POAG, PXFG, and NVG, both with
      and without controlled IOP. The aqueous level of EPO was more proportionate to
      the level of IOP in eyes with PXFG compared to eyes with POAG and NVG.

PMID- 22876127
TI  - Association between cataract and genetic polymorphisms of GSTM1, GSTT1, and GSTO2
      with respect of work place.
AB  - PURPOSE: To investigate whether genetic polymorphisms of glutathione S
      transferases (GSTM1, GSTT1, and GSTO2) in relation to the work place contribute
      to the development of cataract. METHODS: The present case-control study consisted
      of 186 patients (108 females, 78 males) with cataract and 195 gender-matched
      healthy controls (111 females, 84 males) were randomly selected from unrelated
      volunteers in the same clinic. The GSTM1, GSTT1, and GSTO2 genotypes were
      determined using polymerase chain reaction (PCR) based methods. RESULTS: The null
      genotype of GSTM1 increased the risk of cataract (OR=1.51, 95%CI: 1.01-2.26,
      p=0.045). The prevalence of GSTT1 and GSTO2 genotypes was similar between cases
      and controls. There was significant difference between cases and controls for
      work place (chi(2)=4.16, df=1, p=0.041). Genetic polymorphisms (GSTM1, GSTO2) and
      work place that were significant by p<0.3 in the univariate analysis were
      included in the analysis for investigating the additive effects of the genotypes
      and work place on risk of cataract. Statistical analysis showed that the risk of
      cataract increased as a function of number of putative high risk factors
      (chi(2)=8.001, p=0.005). CONCLUSIONS: This finding suggests that the
      polymorphisms of GSTM1 and GSTO2 and also work place may act additively for
      developing cataract.

PMID- 22876128
TI  - Proteomic similarities in steroid responsiveness in normal and glaucomatous
      trabecular meshwork cells.
AB  - PURPOSE: Glucocorticoids (GCs) are common anti-inflammatory agents that can cause
      ocular hypertension and secondary glaucoma as a consequence of impaired aqueous
      humor outflow through the trabecular meshwork (TM). Mechanisms of GC-signaling
      are complex and poorly understood. To better understand GC-signaling in the eye,
      we tested the hypothesis that common mechanisms of steroid responsiveness exist
      in TM cells from normal and glaucomatous donors. METHODS: Four primary cultures
      of human TM cells from normal and glaucomatous donors were treated with or
      without dexamethasone (Dex) for 10 days, then cellular proteins were extracted,
      identified and quantified by liquid chromatography tandem mass spectrometry (LC
      MS/MS) iTRAQ (isobaric tags for relative and absolute quantitation) technology.
      RESULTS: A total of 718 proteins were quantified. Dex-treatment significantly
      altered the abundance of 40 proteins in >=3 cell samples, 37 of which have not
      previously been associated with GC-signaling in TM cells. Most steroid responsive
      proteins were changed in all four TM cells analyzed, both normal and
      glaucomatous. GC-induced proteomic changes support remodeling of the
      extracellular matrix, disorganization of the cytoskeleton/cell-cell interactions,
      and mitochondrial dysfunction. Such physiologic consequences appear common to
      those induced in TM cells by transforming growth factor-beta(2), another putative
      contributor to ocular hypertension and glaucoma pathology. CONCLUSIONS: The
      results expand the repertoire of TM proteins involved in GC-signaling,
      demonstrate common consequences of GC-signaling in normal and glaucomatous TM
      cells, and reveal similarities in proteomic changes induced by steroids and
      TGFbeta(2) in normal and glaucomatous TM cells. Finally, the data contributes to
      a TM quantitative proteomic database.

PMID- 22876129
TI  - TGFBI gene mutations in a Korean population with corneal dystrophy.
AB  - PURPOSE: To investigate the clinical and genetic features of Korean patients with
      corneal dystrophies associated with mutations in the human transforming growth
      factor-beta-induced (TGFBI) gene. METHODS: In this study, 387 subjects (71
      families and 89 individuals - 268 patients having TGFBI corneal dystrophies and
      119 normal relatives) were assessed. All subjects underwent a complete
      ophthalmologic evaluation, including biomicroscopic inspection and dilated fundus
      examination. As a control, 100 individuals without corneal disease were selected
      from the general population. The polymerase chain reaction (PCR) and direct
      sequencing were used to screen for mutations in TGFBI. RESULTS: All subjects
      recruited exhibited a range of corneal dystrophies, including Thiel-Behnke
      corneal dystrophy (TBCD, R555Q; 6 families and 4 individuals), granular corneal
      dystrophy type 2 (GCD2, R124H; 61 families and 80 individuals), lattice corneal
      dystrophy (LCD; 4 families and 5 individuals; 7 with type 1 [R124C], and 2 with a
      variant [L527R, P542R]). The disease showed an autosomal dominant inheritance
      pattern in all families. CONCLUSIONS: R124H in GCD2 was the most common mutation.
      GCD1 and Reis-Bucklers corneal dystrophy were not found. In the GCD2 patients
      there were a large number of laser refractive surgery-induced corneal opacities.
      A spontaneous R124H mutation was confirmed in an already mutated allele that
      resulted in a change from a heterozygous into a homozygous form. Also, a novel
      mutation, P527R, was identified in LCD.

PMID- 22876130
TI  - Genetic analysis of an Indian family with members affected with Waardenburg
      syndrome and Duchenne muscular dystrophy.
AB  - PURPOSE: Waardenburg syndrome (WS) is characterized by sensorineural hearing loss
      and pigmentation defects of the eye, skin, and hair. It is caused by mutations in
      one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated
      transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3),
      SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10).
      Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by
      mutations in the DMD gene. The purpose of this study was to identify the genetic
      causes of WS and DMD in an Indian family with two patients: one affected with WS
      and DMD, and another one affected with only WS. METHODS: Blood samples were
      collected from individuals for genomic DNA isolation. To determine the linkage of
      this family to the eight known WS loci, microsatellite markers were selected from
      the candidate regions and used to genotype the family. Exon-specific intronic
      primers for EDN3 were used to amplify and sequence DNA samples from affected
      individuals to detect mutations. A mutation in DMD was identified by multiplex
      PCR and multiplex ligation-dependent probe amplification method using exon
      specific probes. RESULTS: Pedigree analysis suggested segregation of WS as an
      autosomal recessive trait in the family. Haplotype analysis suggested linkage of
      the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense
      mutation p.T98M in EDN3. A deletion mutation was identified in DMD. CONCLUSIONS:
      This study reports a novel missense mutation in EDN3 and a deletion mutation in
      DMD in the same Indian family. The present study will be helpful in genetic
      diagnosis of this family and increases the mutation spectrum of EDN3.

PMID- 22876131
TI  - Involvement of Smac, p53, and caspase pathways in induction of apoptosis by
      gossypol in human retinoblastoma cells.
AB  - PURPOSE: Retinoblastoma is a malignant tumor of the retina usually occurring in
      young children. To date, the conventional treatments for retinoblastoma have been
      enucleation, cryotherapy, external beam radiotherapy, or chemotherapy. Most of
      these treatments, however, have possible side effects, including blindness,
      infections, fever, gastrointestinal toxicity, and neurotoxicity. More effective
      treatments are therefore imperative. Gossypol has been reported as a potential
      inhibitor of cell proliferation in various types of cancers, such as prostate
      cancer, breast cancer, leukemia, and lung cancer. This study investigates the
      possible antiproliferative effect of gossypol on retinoblastoma. METHODS: Human
      retinoblastoma cells were cultured with various concentrations of gossypol and
      checked for cell viability with a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Nuclear condensation caused by cell
      apoptosis was detected by staining retinoblastoma cells with 4',6-diamidino-2
      phenylindole (DAPI), counting those with condensed nuclei, and determining the
      percentage of apoptotic cells. In addition, the stages of apoptosis and phases in
      cell cycles were examined with flow cytometry. The possible signal transduction
      pathways involved were examined with a protein array assay and western blot
      analysis. RESULTS: After incubation, the cell survival rate was significantly
      lower after treatment with 5, 10, and 20 uM of gossypol. The maximum antisurvival
      effect of gossypol was observed at 20 uM, and the number of apoptotic cells was
      higher in the preparations cultured with 10 and 20 uM of gossypol. The results in
      flow cytometry indicated that at concentrations of 10 and 20 uM, gossypol
      increased the proportion of early- and late-apoptotic retinoblastoma cells and
      induced cell arrest of retinoblastoma cells at the same concentrations. This
      antiproliferative effect was later confirmed by upregulating the expression of
      death receptor 5 (DR5), caspase 8, caspase 9, caspase 3, cytochrome C, tumor
      protein 53 (p53), and second mitochondria-derived activator of caspases (Smac) in
      the signal transduction pathways. CONCLUSIONS: We concluded that gossypol has an
      antiproliferative effect on retinoblastoma cells.

PMID- 22876132
TI  - Application of a high-throughput genotyping method for loci exclusion in non
      consanguineous Australian pedigrees with autosomal recessive retinitis
      pigmentosa.
AB  - PURPOSE: Retinitis pigmentosa (RP) is the most common form of inherited
      blindness, caused by progressive degeneration of photoreceptor cells in the
      retina, and affects approximately 1 in 3,000 people. Over the past decade,
      significant progress has been made in gene therapy for RP and related diseases,
      making genetic characterization increasingly important. Recently, high-throughput
      technologies have provided an option for reasonably fast, cost-effective genetic
      characterization of autosomal recessive RP (arRP). The current study used a
      single nucleotide polymorphism (SNP) genotyping method to exclude up to 28
      possible disease-causing genes in 31 non-consanguineous Australian families
      affected by arRP. METHODS: DNA samples were collected from 59 individuals
      affected with arRP and 74 unaffected family members from 31 Australian families.
      Five to six SNPs were genotyped for 28 genes known to cause arRP or the related
      disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to
      exclude possible causative genes from each of the 31 families. Bidirectional
      sequencing was used to identify disease-causing mutations in prioritized genes
      that were not excluded with cosegregation analyses. RESULTS: Two families were
      excluded from analysis due to identification of false paternity. An average of
      28.9% of genes were excluded per family when only one affected individual was
      available, in contrast to an average of 71.4% or 89.8% of genes when either two,
      or three or more affected individuals were analyzed, respectively. A
      statistically significant relationship between the proportion of genes excluded
      and the number of affected individuals analyzed was identified using a
      multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in
      identification of the likely disease-causing gene as CRB1 in one family (c.2548
      G>A) and USH2A in two families (c.2276 G>T). CONCLUSIONS: This study has shown
      that SNP genotyping cosegregation analysis can be successfully used to refine and
      expedite the genetic characterization of arRP in a non-consanguineous population;
      however, this method is effective only when DNA samples are available from more
      than one affected individual.

PMID- 22876133
TI  - ATRA enhances the bystander effect of suicide gene therapy driven by the specific
      promoter LEP 503 in human lens epithelial cells.
AB  - PURPOSE: To establish a novel, targeted lentivirus-mediated LEP503-HSV-tk/GCV
      suicide gene therapy system combined with all trans-retinoic acid (ATRA) for the
      inhibition of human lens epithelial cell (HLEC) proliferation and treatment of
      posterior capsular opacification (PCO) after cataract surgery; to estimate the
      enhancement of the bystander effect by ATRA; and to explore the role of
      Connexin43 (Cx43) mediated gap junctional intercellular communication (GJIC) in
      the bystander effect of the HSV-K/GCV system. METHODS: A Lenti-LEP503-HSV-tk-EGFP
      vector was generated by cloning the lens-specific promoter LEP503 (lens specific
      promoter 503) from genomic DNA of HLECs by PCR. The vector was then inserted into
      the promoter-less vector from lentivirus-based (CMV)-HSV-tk-EGFP. The
      expressional specificity of the LEP503 promoter was assessed by investigating the
      expression of EGFP (enhanced green fluorescent protein) and HSV-tk (herpes
      simplex virus thymidine kinase) mRNA, both driven by Lenti-LEP503-HSV-tk-EGFP
      vector, by fluorescence microscopy, RT-PCR, flow cytometry, and western blot
      assays in HLECs, human adult retinal pigment epithelium cells (RPECs), human
      adult skin fibroblast cells (ASFCs), and Hela cells. Morphological changes were
      observed by fluorescence microscopy and cell viability was determined using the
      Cell Counting kit-8 Cell Proliferation (CCK-8) and MTT (3-(4,5-Dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) assays after Lenti-LEP503-HSV-tk/GCV system
      combined with ATRA treatment on HLECs. Flow cytometry, DNA fragmentation, and
      western blot assays were employed to analyze the mechanisms of bystander effects.
      RESULTS: The promoter LEP503-mediated HSV-tk was specifically expressed in HLECs,
      and ATRA dose-dependently strengthened the bystander effect following LEP503
      mediated HSV-tk/GCV gene therapy against lens cells by upregulating the
      expression of the gap junction protein Cx43. CONCLUSIONS: The Lenti-LEP503-HSV
      tk/GCV suicide gene therapy system, combined with ATRA as an adjuvant, may be a
      feasible supplementary method for PCO treatment that targets residual lens cells.

PMID- 22876134
TI  - Deciphering the potential efficacy of acetyl-L-carnitine (ALCAR) in maintaining
      connexin-mediated lenticular homeostasis.
AB  - PURPOSE: To determine the putative role of acetyl-L-carnitine (ALCAR) in
      maintaining normal intercellular communication in the lens through connexin.
      METHODS: In the present study, Wistar rat pups were divided into 3 groups of
      eight each. On postpartum day ten, Group I rat pups received an intraperitoneal
      injection (50 ul) of 0.89% saline. Rats in Groups II and III received a
      subcutaneous injection (50 ul) of sodium selenite (19 umol/kg bodyweight); Group
      III rat pups also received an intraperitoneal injection of ALCAR (200 mg/kg
      bodyweight) once daily on postpartum days 9-14. Both eyes of each pup were
      examined from day 16 up to postpartum day 30. Alterations in the mean activity of
      the channel pumps, calcium-ATPase and sodium/potassium-ATPase, were determined.
      The expression of genes encoding key lenticular gap junctions (connexin 46 and
      connexin 50) and a channel pump (plasma membrane Ca(2+)-ATPase [PMCA1]) was
      evaluated by reverse transcription-PCR. Immunoblot analysis was also performed to
      confirm the differential expression of key lenticular connexin proteins. In
      addition, bioinformatics analysis was performed to determine the interacting
      residues of the connexin proteins with ALCAR. RESULTS: Significantly lower mean
      activities of Ca(2+)-ATPase and Na(+)/K(+) -ATPase were observed in the lenses of
      Group II rats than those in Group I rat lenses. However, the observed mean
      activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase in Group III rat lenses were
      significantly higher than those in Group II rat lenses. The mean mRNA transcript
      levels of the connexin 46 and connexin 50 genes were significantly lower, while
      the mean levels of PMCA1 gene transcripts were significantly higher, in Group II
      rat lenses than in Group I rat lenses. Immunoblot analysis also confirmed the
      altered expression of connexin proteins in lysates of whole lenses of Group II
      rats. However, the expression of connexin 46 and connexin 50 proteins in lenses
      from group III rats was essentially similar to that noted in lenses from normal
      (Group I) rats. Hydrogen bond-interaction between ALCAR and amino acid residues
      at the functional domain regions of connexin 46 and connexin 50 proteins was also
      demonstrated through bioinformatics tools. CONCLUSIONS: The results suggest that
      ALCAR plays a key role in maintaining lenticular homeostasis by promoting gap
      junctional intercellular communication.

PMID- 22876135
TI  - Stem cells isolated from the human stromal limbus possess immunosuppressant
      properties.
AB  - PURPOSE: Mesenchymal stromal stem cells (MSC) are non-hemopoietic cells with the
      capacity to self-renewal and to differentiate into various cell lineages of
      mesenchymal origin. More recently, the immune regulatory potential of MSC has
      been focused on. Furthermore, mesenchymal stem cells obtained from diverse
      tissues possess immunomodulatory properties and inhibit proinflammatory immune
      reactions. The aim of this study was to determine the immunosuppressive
      characteristics of mesenchymal stem cells isolated from human limbal (L-MSC)
      tissue. METHODS: L-MSC were enzymatically obtained from cadaveric sclero-corneal
      rims and expanded in vitro. The cells were characterized by flow cytometry using
      specific antibodies to mesenchymal stem cells markers. Clonogenic and tissue
      transdifferentiation in vitro assays were performed. The effect of L-MSC soluble
      factors on T cell proliferation was determined by flow cytometry. Cytokines such
      as transforming growth factor-b1 (TGF-beta1) and Interleukin-10 (IL-10) on
      supernatants from L-MSC were identified by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Herein, we described that L-MSC cells in vitro-expanded were
      positive for the expression of vimentin, CD29, CD34, CD39, CD73 and CD105
      mesenchymal stem cells markers; meanwhile, this cell population was negative to
      CD45 and HLA-DR hemopoietic markers as well as to cytokeratin expression.
      Clonogenic assays showed that these cells were able to form colonies. In
      addition, this L-MSC population had the ability to transdifferentiate into
      neurons and chondrocytes and to form tubular networks on matrigel in the presence
      of vascular endothelial growth factor (VEGF). These results indicated that these
      cells were stem cells. Additionally, soluble factors secreted by L-MSC were
      capable of mediating the suppression of T-cell receptor (TCR)-engagement
      lymphocyte proliferation. In an attempt to identify the possible
      immunosuppressive factors secreted by L-MSC, TGFbeta1 and IL-10 cytokines were
      determined in the L-MSC supernatants by ELISA; interestingly, TGFbeta1 was
      constitutively secreted by this cell population; in contrast, IL-10 was not
      detectable. Moreover, TGFbetaRII neutralizing antibodies were able to revert the
      TCR-engagement lymphocyte proliferation inhibition mediated by L-MSC. Thus,
      TGFbeta1 secreted by L-MSC was able to suppress T cell proliferation.
      CONCLUSIONS: Taken together these results, explain in part the immunosuppressive
      features of this cell population obtained from the human limbus. All these
      characteristics make this cell population an excellent source to be used in the
      regenerative medicine.

PMID- 22876136
TI  - p38 mitogen-activated protein kinase-induced nuclear factor kappa-light-chain
      enhancer of activated B cell activity is required for neuroprotection in retinal
      ischemia/reperfusion injury.
AB  - PURPOSE: In our previous study, nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB) played a neuroprotective role in retinal
      ischemia/reperfusion (I/R) injury in rats. However, the mechanism of NF-kappaB
      neuroprotection is still unclear. We hypothesize that p38 mitogen-activated
      protein kinase (MAPK) is expressed and NF-kappaB activity induced by p38 MAPK
      plays a neuroprotective role through antiapoptotic genes (B-cell lymphoma [Bcl]-2
      and Bcl-XL) in retinal cells in retinal I/R injury. METHODS: Retinal ischemia was
      induced by elevating intraocular pressure in rats. After retinal I/R, the p38
      MAPK, NF-kappaB p65, Bcl-2, and Bcl-XL mRNA levels were measured with real-time
      polymerase chain reaction. NF-kappaB p65 activity was assessed with NF-kappaB
      enzyme-linked immunosorbent assay in retinal I/R injury and after application of
      the p38 MAPK inhibitor (SB203580). Furthermore, SB203580 and NF-kappaB p65 short
      interfering RNA (siRNA) were used in retinal I/R injury to examine the effects on
      Bcl-2 and Bcl-XL levels and nucleosome release in the retina and cell survival in
      the ganglion cell layer. RESULTS: The mRNA levels of NF-kappaB p65 and p38 MAPK
      reached a peak at 6 h after retinal I/R and then decreased gradually. The mRNA
      levels of Bcl-2 and Bcl-XL significantly increased at 2, 4, and 6 h, peaked at 8
      h, and decreased gradually, but remained at a higher level compared with the
      normal control, which was accompanied by an increase in NF-kappaB p65 in nuclear
      extracts. After application of SB203580, the increase in the NF-kappaB p65 levels
      in the nucleus induced with I/R was completely abolished, and the mRNA expression
      of Bcl-2 and Bcl-XL decreased significantly compared with the I/R controls. In
      addition, NF-kappaB p65 siRNA inhibited Bcl-2 and Bcl-XL expression. Inhibition
      of the p38 MAPK-NF-kappaB pathway (using SB203580 or NF-kappaB p65 siRNA)
      increased retinal nucleosome release and decreased the number of ganglion cells.
      CONCLUSIONS: These findings provide evidence of crosstalk between p38 MAPK and NF
      kappaB p65 and demonstrate a possible neuroprotective role for the p38 MAPK-NF
      kappaB pathway through Bcl-2 and Bcl-XL in retinal I/R injury in rats.

PMID- 22876138
TI  - A novel mutation in GJA3 associated with congenital Coppock-like cataract in a
      large Chinese family.
AB  - PURPOSE: To identify the potential pathogenic mutation over five generations of a
      Chinese family with congenital Coppock-like cataracts (CCL). METHODS: We
      investigated five generations of a Chinese family affected with CCL. The family
      resides in a relatively isolated region of northern China. Peripheral blood
      samples were collected from all of the family members, and genomic DNA was then
      extracted from the blood samples. A genome-wide linkage scan was performed using
      about 400 microsatellite markers. Two-point LOD (linkage odd disequilibrium)
      scores (Z) were calculated using the LINKAGE programs (ver. 5.1). Cyrillic
      software processed the resulting haplotypes. Mutation detection was performed in
      the candidate gene by direct sequencing. RESULTS: The maximum LOD score was
      obtained at marker D13S175 (lod score [Z(max)]=5.90; recombination fraction
      [theta]=0.0). Haplotype analysis traced the disease gene to a 6.99-cM interval
      bounded by D13S1316 and D13S1275 on chromosome 13q12.11. Direct sequencing of the
      candidate gene GJA3 (gap junction protein alpha-3) revealed a c.427G>A transition
      in exon 2 of GJA3 that co-segregated with the cataract in the family members and
      was not observed in 100 control patients. This single-nucleotide change resulted
      in the substitution of a highly conserved glycine by arginine (G143R).
      CONCLUSIONS: The present study identified a novel mutation in GJA3 that causes
      CCL. As the first report to relate p.G143R mutation in GJA3, it expands the
      mutation spectrum of GJA3. Our report is the first in identification of the
      mutation of GJA3 in the cytoplasmic-loop domain. This mutation is associated with
      multiple members of a five-generation family with congenital CCL.

PMID- 22876137
TI  - Significant association between insertion/deletion polymorphism of the
      angiotensin-convertig enzyme gene and ankylosing spondylitis.
AB  - PURPOSE: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease
      that characteristically affects the sacroiliac joints and the spine. Also iritis
      and uveitis can be serious complications of AS that can damage the eye and impair
      vision. The exact pathogenesis of AS remains poorly understood but genetic
      factors play a key role in its development. Human leukocyte antigen B27 (HLA-B27)
      is the major genetic susceptibility marker in AS. To our knowledge, angiotensin
      converting enzyme (ACE) gene I/D polymorphisms have not yet been investigated in
      AS patients in Turkish population.This study was conducted in Turkish patients
      with AS to determine the frequency of I/D polymorphism genotypes of angiotensin
      converting enzyme gene. METHODS: Genomic DNA obtained from 262 persons (122
      patients with ankylosing spondylitis and 140 healthy controls) was used in the
      study. ACE I/D polymorphism genotypes were determined by using polymerase chain
      reaction with specific primers. RESULTS: There was statistically significant
      difference between the groups with respect to genotype distribution (p<0.001).
      When we examine ACE genotype frequencies according to the clinical
      characteristics there was a statistically significant association between DD
      genotype and ocular involvement (p=0.04) also sacroiliac joint involvement
      (p=0.03). CONCLUSIONS: As a result of our study, angiotensin converting enzyme
      gene I/D polymorphism DD genotype could be a genetic marker in ankylosing
      spondylitis in a Turkish study population.

PMID- 22876139
TI  - Screening of candidate genes for primary open angle glaucoma.
AB  - PURPOSE: Primary open-angle glaucoma (POAG) is one of the leading causes of
      irreversible blindness in the world. To make progress in understanding POAG, it
      is necessary to identify more POAG-causing genes. METHODS: Using haplotype
      analysis, we found that mutational region is located on chromosome 2 in two
      families. Furthermore, we screened 11 candidate genes on chromosome 2 by protein
      protein interaction (PPI) analysis, including mutS homolog 6 (MSH6), mutS homolog
      2 (MSH2), v-rel reticuloendotheliosis viral oncogene homolog (REL), endothelial
      PAS domain protein 1 (EPAS1), vaccinia related kinase 2 (VRK2), F-box protein 11
      (FBXO11), EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1),
      reticulon 4 (RTN4), RAB1A, member RAS oncogene family (RAB1A), ARP2 actin-related
      protein 2 homolog (ACTR2), and calmodulin 2 (phosphorylase kinase, delta; CALM2).
      These 11 genes are all predicted to be related to trabecular meshwork changes and
      progressive loss of retinal ganglion cells in POAG patients. RESULTS: According
      to our study, FBXO11 and VRK2 may interact with tumor protein p53 to regulate
      mitochondrial membrane permeability, mitochondrial membrane organization, and
      apoptosis. MSH2 is responsible for repairing DNA mismatches and RTN4 is for
      neuronal regeneration. Therefore, they are supposed to play a negative role in
      cellular process in POAG. CALM2 may be involved in retinal ganglion cell death
      and oxidative damage to cell communication. CONCLUSIONS: The results demonstrate
      that the genes above may be associated with pathogenesis of POAG.

PMID- 22876140
TI  - Inhibition of p38 mitogen-activated protein kinase phosphorylation decrease tert
      butyl hydroperoxide-induced apoptosis in human trabecular meshwork cells.
AB  - PURPOSE: Oxidative stress induced trabecular meshwork cells death is believed to
      be involved in the pathogenesis and progression of primary open-angle glaucoma
      (POAG). However, the intrinsic mechanism is yet to be clarified. This study is to
      investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in tert
      butyl hydroperoxide (tBHP)-induced apoptosis of human trabecular meshwork (iHTM)
      cells. METHODS: The human trabecular meshwork cells were treated with tBHP for 1
      or 2 h with or without pretreatment of SB203580, an inhibitor of MAP kinase
      homologs. Cell viability was analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5
      diphenyl-2h-tetrazolium bromide assay. Reactive oxygen species (ROS) levels were
      determined using dihydrodichlorofluorescein staining, and the chymotrypsin-like
      protease activities were measured using the Suc-LLVY-aminoluciferin substrate.
      Cell apoptosis was analyzed by Hoechst 33258 staining and annexin V-PI labeling.
      The protein level of phospho-p38 was measured using western blot analysis.
      RESULTS: The intracellular ROS increased more than 50 fold and more than 100 fold
      after tBHP exposure for 1 h and 2 h, respectively (p<0.05). However, there was no
      difference in ROS levels between SB203580(-) and SB203580(+) cells (p>0.05). In 1
      h tBHP treatment group, the cell viability was significantly improved in
      SB203580(+) cells (81.08%+/-1.93%) compared to the SB203580(-) cells (69.35%+/
      1.52%), the chymotrypsin-like proteasome inactivation decreased in SB203580(+)
      cells (60.94%+/-0.55%) compared to the SB203580(-) cells (70.59%+/-0.88%), and
      apoptosis was impoved in SB203580(+) cells (12.75%+/-1.91%) compared to the
      SB203580(-) (28.23%+/-3.23%) (p<0.05). In 2 h tBHP treatment group, cell
      viability improved in SB203580(+) cells (76.72%+/-2.11%) compared to SB203580(-)
      cells (57.88%+/-2.20%), chymotrypsin-like proteasome inactivation was improved in
      SB203580(+) cells (62.99%+/-0.41%) compared to SB203580(-) cells (74.93%+/
      0.54%), and apoptosis was improved in SB203580(+) cells (20.40%+/-3.44%) compared
      to SB203580(-) cells (39.20%+/-5.91%) (p<0.05). Phosphorylation of p38MAPK was
      significantly increased after tBHP exposure in SB203580 (-) cells and decreased
      sharply in SB203580(+) cells than that of control group (p<0.05). While there was
      no difference on the original form of p38MAPK among SB203580(-) and SB203580(+)
      cells after tBHP exposure and control group (p>0.05). CONCLUSIONS: Activation of
      p38MAPK plays an important role in tBHP-induced apoptosis of iHTM cells. Further
      study on the mechanisms of p38MAPK in human TM cell apoptosis may help to
      illuminate the pathogenesis of POAG.

PMID- 22876141
TI  - Amniotic membrane traps and induces apoptosis of inflammatory cells in ocular
      surface chemical burn.
AB  - PURPOSE: Severe chemical burns can cause necrosis of ocular surface tissues
      following the infiltration of inflammatory cells. It has been shown that amniotic
      membrane transplantation (AMT) is an effective treatment for severe chemical
      burns, but the phenotypes of cells that infiltrate the amniotic membrane and the
      clinical significance of these cellular infiltrations have not previously been
      reported. The present work studies the inflammation cell traps and apoptosis
      inducing roles of the amniotic membrane after AMT in patients with acute chemical
      burns. METHODS: A total of 30 patients with acute alkaline burns were classified
      as having either moderate or severe burns. In all participants, AMT was performed
      within one week of his/her injury. After 7-9 days, the transplanted amniotic
      membranes were removed. Histopathological and immunohistochemical techniques were
      used for the examination and detection of infiltrating cells, and tests for the
      expression of CD (cluster of differentiation)15, CD68, CD3, CD20, CD57, CD31,
      CD147, and CD95 (Fas) were performed. A TUNEL (TdT-mediated dUTP nick end
      labeling) assay was used to confirm apoptosis of the infiltrating cells. Three
      patients with herpes simplex-induced keratitis who had undergone AMT to treat
      persistent epithelium defects were used as a control group. Amniotic membrane
      before transplantation was used as another control. RESULTS: After amniotic
      membrane transplantation, the number of infiltrating cells in patients with
      severe burns was significantly higher than in patients with moderate burns or in
      control patients (p<0.05). Among the severe burns patients, CD15 and CD68 were
      widely expressed in the infiltrating cells, and CD3, CD20, and CD57 were only
      found in a small number of cells. Occasionally, CD31-positive cells were found in
      the amniotic membranes. More cells that were CD147, Fas, and TUNEL positive were
      found in patients with severe burns than in patients with moderate burns or in
      control patients. CONCLUSIONS: Neutrophils and macrophages were the main cells
      that had infiltrated into the amniotic membrane during the acute phase of healing
      from a chemical burns. AMT can trap different inflammatory cells and induce
      apoptosis of inflammatory cells in acute ocular chemical burns.

PMID- 22876143
TI  - Psychosocial aspects of cancer need integration into the treatment trajectory-but
      how?

PMID- 22876142
TI  - A practical approach to optic nerve crush in the mouse.
AB  - Our goal is to provide an instructional resource to help others wishing to use
      the optic nerve crush (ONC) as an experimental procedure. The process is
      described beginning with the anesthesia, followed by positioning of the mouse,
      the surgery itself, and post-surgical care. We analyzed the effect of ONC on
      retinal blood flow, using optical coherence tomography doppler. This procedure
      produces a consistent loss of cells in the ganglion cell layer, using whole
      mounts of retina stained with TO-PRO-3. An instructional video is presented that
      demonstrates a simple surgical approach to effectively crush the optic nerve of
      the mouse.

PMID- 22876144
TI  - Is breast cancer staging obsolete?

PMID- 22876145
TI  - Outcomes of women with early-stage breast cancer receiving adjuvant trastuzumab.
AB  - INTRODUCTION: Large randomized trials assessing the benefit of adjuvant
      trastuzumab in early-stage breast cancer positive for the human epidermal growth
      factor receptor 2 (her2) have demonstrated a significant improvement in survival.
      The objective of the present study was to describe the outcomes of women who
      received adjuvant trastuzumab for her2-positive breast cancer in British Columbia
      since publicly funded population-based use was initiated in July 2005. METHODS:
      Women from British Columbia, newly diagnosed with stage i-iii breast cancer
      between July 2004 and December 2006, who were positive for her2 overexpression by
      immunohistochemistry (3+) or amplification by fluorescence in situ hybridization
      (ratio >= 2.0) were included in the study. Data were collected from the
      prospectively assembled BC Cancer Agency Outcomes Unit, with cases linked to the
      provincial pharmacy data repository to determine the proportion of women who
      received adjuvant trastuzumab. RESULTS: Our retrospective study identified 703
      her2-positive patients, of whom 480 (68%) received trastuzumab. In patients
      receiving trastuzumab, the 2-year relapse-free survival was 96.1% [95% confidence
      interval (CI): 93.6% to 97.7%] and the overall survival was 99.3% (95% CI: 97.9%
      to 99.8%). Among node-negative and -positive patients, the 2-year relapse-free
      survival was 97.8% and 94.8% respectively (p = 0.09) for the trastuzumab-treated
      group and 90.9% and 77.3% (p = 0.01) for the group not receiving trastuzumab (n =
      223). Site of first distant metastasis was the central nervous system in 19.5% of
      the entire cohort and in 37.5% of patients treated with trastuzumab. DISCUSSION:
      This population-based analysis of adjuvant trastuzumab use among Canadian women
      demonstrates highly favorable outcomes at the 2-year follow-up.

PMID- 22876146
TI  - Hypertension management in patients with renal cell cancer treated with anti
      angiogenic agents.
AB  - Inhibitors of the vascular endothelial growth factor (vegf-is) signalling pathway
      have fundamentally changed the treatment of metastatic renal cell carcinoma
      (mrcc). Hypertension is one of the most common side effects of vegf-is and has
      been reported with almost every vegf-i used for treatment to date. The exact
      mechanism of vegf-i-induced hypertension appears complex and multifactorial, and
      it remains to be fully explained. No randomized clinical trials are available to
      guide the management of hypertension during vegf-i treatment in mrcc patients.
      The guiding principles suggested here summarize the consensus of opinions on the
      diagnosis and management of vegf-i-induced hypertension during treatment of mrcc
      obtained from an expert working group composed of 4 Canadian medical oncologists
      and 5 Canadian hypertension specialists. The Canadian Hypertension Education
      Program guidelines, available literature, and expert opinion were used to develop
      the guiding principles.

PMID- 22876147
TI  - Psychosocial care for cancer: a framework to guide practice, and actionable
      recommendations for Ontario.
AB  - OBJECTIVES: We set out to create a psychosocial oncology care framework and a set
      of relevant recommendations that can be used to improve the quality of
      comprehensive cancer care for Ontario patients and their families.meet the
      psychosocial health care needs of cancer patients and their families at both the
      provider and system levels. DATA SOURCES AND METHODS: The adapte process and the
      practice guideline development cycle were used to adapt the 10 recommendations
      from the 2008 U.S. Institute of Medicine standard Cancer Care for the Whole
      Patient: Meeting Psychosocial Health Needs into the psychosocial oncology care
      framework. In addition, the evidence contained in the original document was used,
      in combination with the expertise of the working group, to create a set of
      actionable recommendations. Refinement after formal external review was
      conducted. DATA EXTRACTION AND SYNTHESIS: The new framework consists of 8
      defining domains. Of those 8 domains, 7 were adapted from recommendations in the
      source document; 1 new domain, to raise awareness about the need for psychosocial
      support of cancer patients and their families, was added. To ensure high-quality
      psychosocial care and services, 31 actionable recommendations were created. The
      document was submitted to an external review process. More than 70% of
      practitioners rated the quality of the advice document as high and reported that
      they would recommend its use. CONCLUSIONS: This advice document advocates for a
      multidisciplinary approach to cancer care in response to the distress experienced
      by cancer patients and their families. The recommendations will be useful in
      future to measure performance, quality of practice, and access to psychosocial
      services.

PMID- 22876148
TI  - Liver transplantation for symptomatic liver metastases of neuroendocrine tumours.
AB  - Numerous reports have demonstrated that liver transplantation for neuroendocrine
      tumour metastasis is feasible. However, perioperative risks and long-term
      recurrences remain significant concerns. When liver transplantation is combined
      with extensive intestinal or pancreatic resection, the risk is particularly
      high.We report our institutional experience of liver transplantations performed
      for liver metastases secondary to neuroendocrine tumours, and in combination with
      a review of the literature, we propose a set of selection criteria. The key
      points include unresectable hepatic metastases of neuroendocrine origin, absence
      of extrahepatic metastases, symptomatic disease that is refractory to medical
      therapy, a Ki-67 level less than 2%, previous resection of the primary disease,
      and previous therapy for metastatic neuroendocrine tumour.In our experience, the
      patient in the first case had, post-transplantation, rapid disease progression
      because of an unidentified primary, and patient in the second case had primary
      non-function of the liver graft, requiring urgent re-transplantation. More
      recently, two liver transplantations were successfully performed. The indications
      were, in the first case, refractory hormonal secretion and, in the other,
      secondary biliary cirrhosis attributable to hepatic artery therapy with tumour in
      situ. Subclinical and stable recurrent disease has been detected by scintigraphy
      in the mesentery and lumbar spine in the former patient. A mesenteric recurrence
      developed in the latter patient 2 years post transplantation and was subsequently
      completely resected. At 4 and 5 years post transplantation, both patients are
      symptom-free.Recurrence after transplantation remains a significant concern, even
      with careful patient selection, but recurrences may remain indolent. If
      recurrences are progressive, they may still be amenable to additional medical or
      surgical therapy. A national or international consensus between oncologists and
      transplant specialists regarding the indications for liver transplantation is
      vital, because future progress will depend on careful patient selection and
      prospective study.

PMID- 22876149
TI  - Conditional survival in Canada: adjusting patient prognosis over time.

PMID- 22876150
TI  - Tobacco and health: with or without pictures, nothing redeems smoking.

PMID- 22876151
TI  - Multidisciplinary management of cancer patients: chasing a shadow or real value?
      An overview of the literature.
AB  - PURPOSE: Multidisciplinary cancer conferences (mccs) are designed to optimize
      patient outcomes. It appears intuitive that mccs are essential to clinical
      decision-making and patient management; however, it is unclear whether that
      belief is supported by evidence. Our objectives were to assess the currently
      published literature addressing the impact of mccs on clinical decision-making
      and patient outcomes. METHODS: Ovid medline was searched from 1950 to June 2010
      using these keywords: "multidisciplinary/interdisciplinary/clinical
      meeting$/conference$/round$/team$," "decision making,"
      "neoplasms$/cancer$/oncology/tumo(u)r conference$/board$/meeting$,"
      "multidisciplinary/interdisciplinary cancer conference$/meeting$." All trials,
      guidelines, metaanalyses, reviews, and prospective and retrospective studies were
      included. RESULTS: The keywords retrieved 595 abstracts, and 30 manuscripts were
      obtained. Most of the studies assessed the impact of mccs on clinical decision
      making rather than on patient outcomes. CONCLUSIONS: Available evidence supports
      the belief that mccs significantly influence clinical decision-making and
      treatment recommendations. In contrast, scant evidence suggests that mccs improve
      patient outcomes. Unfortunately, the current literature is substantially
      heterogeneous and therefore does not allow for firm conclusions.

PMID- 22876152
TI  - Use and delivery of granulocyte colony-stimulating factor in breast cancer
      patients receiving neoadjuvant or adjuvant chemotherapy-single-centre experience.
AB  - BACKGROUND: Use of granulocyte colony-stimulating factor (g-csf) as primary
      prophylaxis against chemotherapy-induced neutropenia has significant cost
      implications. We examined use of g-csf for early-stage breast cancer patients at
      our centre. The study also examined the pattern of nurse-led patient teaching
      with respect to drug self-administration. METHODS: Patients who received g-csf
      between November 2009 and October 2010 were identified from pharmacy records.
      After consent had been obtained, electronic charts were examined to extract data
      on chemotherapy and use of g-csf. Patients were contacted by telephone to obtain
      information on the utilization of home-care nursing visits for g-csf
      administration. RESULTS: The study analyzed 36 patients. Median age was 58 years
      (range: 31-78 years). Of the 36 patients, 30 (83%) had received adjuvant
      treatment, and 6 (17%), neoadjuvant treatment. Most patients (71%) received 10
      days (range: 7-10 days) of filgrastim. Of the 36 patients, 29 (81%) received g
      csf as primary prophylaxis. In 90% of those patients, primary prophylaxis
      commenced with the taxane component of treatment. Of the 36 patients, 7 (19%)
      received g-csf after neutropenia, including 2 who had febrile neutropenia. In 96%
      of the patients, injections were received at home with the help of a nurse; those
      patients were subsequently taught self-injection techniques. The median number of
      nursing visits was 2 (range: 1-3 visits). Most patients were satisfied with the
      home care and g-csf teaching they received. CONCLUSIONS: Most of the g-csf used
      in breast cancer treatment during the study period was given for primary
      prophylaxis. A major reason for the decision to use g-csf appears to have been
      physician-perceived risk of febrile neutropenia. Delivery of g-csf by home-care
      nurses was well received by patients.

PMID- 22876154
TI  - Effects of radiation and total androgen blockade on serum hemoglobin,
      testosterone, and erythropoietin in patients with localized prostate cancer.
AB  - OBJECTIVE: The objective of the present study was to evaluate the incidence, time
      of onset, and extent of hemoglobin, testosterone, and erythropoietin changes in
      patients with localized prostate cancer receiving either radiation alone or
      radiation combined with total androgen blockade (tab). METHODS: The study
      enrolled 35 patients (median age: 69 years) with clinically localized prostate
      cancer who received 3-dimensional conformal radiation with or without tab.
      Patients were generally treated with radiation alone (group 1), radiation plus
      short-term (<=6 months) tab (group 2), or radiation plus long-term (>=2 years)
      tab (group 3). Serum hemoglobin, testosterone, and erythropoietin in these
      patients were prospectively evaluated. RESULTS: The mean baseline serum
      hemoglobin for group 1 (n = 20), group 2 (n = 6), and group 3 (n = 9) was 149
      g/L, 153 g/L, and 143 g/L respectively. We observed no significant decline in
      serum hemoglobin, testosterone, or erythropoietin among patients treated with
      radiotherapy alone. A significant drop in serum testosterone was noted in the
      group 2 and 3 patients within 1 month (p < 0.001), reaching a plateau at
      approximately 6 months. That change was followed by a significant decline (p <
      0.001) in serum hemoglobin at 3-6 months (137 g/L in group 2 and 129 g/L in group
      3). We observed a small but statistically significant increase in serum
      erythropoietin (p < 0.001) of 8 U/L in group 2 and 4 U/L in group 3 after 6
      months of tab. No immediate recovery in serum hemoglobin, testosterone, or
      erythropoietin was observed upon completion of tab. CONCLUSIONS: Although
      conformal radiotherapy alone for localized prostate cancer had no effect on serum
      hemoglobin, testosterone, or erythropoietin, tab led to a significant decline in
      testosterone, which was followed by decline in hemoglobin that was not a result
      of a deficiency of erythropoietin.

PMID- 22876155
TI  - Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell
      lung cancer.
AB  - PURPOSE: Outcomes after treatment with accelerated hypofractionated radiotherapy
      in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were
      determined. METHODS: Our single-institution retrospective review looked at
      medically inoperable patients with T1-2N0M0 nsclc treated with accelerated
      hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients
      were staged mainly by computed tomography imaging of chest and abdomen, bone
      scan, and computed tomography/magnetic resonance imaging of brain. Positron
      emission tomography (pet) staging was performed in 6 patients. Medical charts
      were reviewed to determine demographics, radiotherapy details, sites of failure,
      toxicity (as defined by the Common Terminology Criteria for Adverse Events,
      version 3.0) and vital status. The cumulative incidence of local and distant
      failure was calculated. Overall (os) and cause-specific (css) survival were
      estimated by the Kaplan-Meier method. RESULT: In the 60 patients treated during
      the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in
      20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions
      (n = 4). All patients were treated once daily. The median follow-up was 27 months
      (range: 4-94 months). The os rates at 2 and 5 years were 61% [95% confidence
      interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css
      rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%)
      respectively. The cumulative incidence of local failure was 20% at 5 years. The
      cumulative incidence of distant failure was 28% at 5 years. No patients
      experienced grade 3 or greater pneumonitis or esophagitis. CONCLUSIONS:
      Accelerated hypofractionated regimens are well tolerated and provide good local
      control in medically inoperable patients with stage i nsclc. Such regimens may be
      a reasonable treatment alternative when stereotactic body radiation therapy is
      not feasible.

PMID- 22876153
TI  - Management of a suspicious adnexal mass: a clinical practice guideline.
AB  - QUESTIONS: What is the optimal strategy for preoperative identification of the
      adnexal mass suspicious for ovarian cancer? What is the most appropriate surgical
      procedure for a woman who presents with an adnexal mass suspicious for
      malignancy? PERSPECTIVES: In Canada in 2010, 2600 new cases of ovarian cancer
      were estimated to have been diagnosed, and of those patients, 1750 were estimated
      to have died, making ovarian cancer the 7th most prevalent form of cancer and the
      5th leading cause of cancer death in Canadian women. Women with ovarian cancer
      typically have subtle, nonspecific symptoms such as abdominal pain, bloating,
      changes in bowel frequency, and urinary or pelvic symptoms, making early
      detection difficult. Thus, most ovarian cancer cases are diagnosed at an advanced
      stage, when the cancer has spread outside the pelvis. Because of late diagnosis,
      the 5-year relative survival ratio for ovarian cancer in Canada is only 40%.
      Unfortunately, because of the low positive predictive value of potential
      screening tests (cancer antigen 125 and ultrasonography), there is currently no
      screening strategy for ovarian cancer. The purpose of this document is to
      identify evidence that would inform optimal recommended protocols for the
      identification and surgical management of adnexal masses suspicious for
      malignancy. OUTCOMES: Outcomes of interest for the identification question
      included sensitivity and specificity. Outcomes of interest for the surgical
      question included optimal surgery, overall survival, progression-free or disease
      free survival, reduction in the number of surgeries, morbidity, adverse events,
      and quality of life. METHODOLOGY: After a systematic review, a practice guideline
      containing clinical recommendations relevant to patients in Ontario was drafted.
      The practice guideline was reviewed and approved by the Gynecology Disease Site
      Group and the Report Approval Panel of the Program in Evidence-based Care.
      External review by Ontario practitioners was obtained through a survey, the
      results of which were incorporated into the practice guideline. PRACTICE
      GUIDELINE: These recommendations apply to adult women presenting with a
      suspicious adnexal mass, either symptomatic or asymptomatic.  IDENTIFICATION OF
      AN ADNEXAL MASS SUSPICIOUS FOR OVARIAN CANCER: Sonography (particularly 3
      dimensional sonography), magnetic resonance imaging (mri), and computed
      tomography (ct) imaging are each recommended for differentiating malignant from
      benign ovarian masses. However, the working group offers the following further
      recommendations, based on their expert consensus opinion and a consideration of
      availability, access, and harm: Where technically feasible, transvaginal
      sonography should be the modality of first choice in patients with a suspicious
      isolated ovarian mass.To help clarify malignant potential in patients in whom
      ultrasonography may be unreliable, mri is the most appropriate test.In cases in
      which extra-ovarian disease is suspected or needs to be ruled out, ct is the most
      useful technique.Evaluation of an adnexal mass by Doppler technology alone is not
      recommended. Doppler technology should be combined with a morphology
      assessment.Ultrasonography-based morphology scoring systems can be used to
      differentiate benign from malignant adnexal masses. These scoring systems are
      based on specific ultrasound parameters, each with several scores base on
      determined features. All evaluated scoring systems were found to have an
      acceptable level of sensitivity and specificity; the choice of scoring system may
      therefore be made based on clinician preference.As a standalone modality, serum
      cancer antigen 125 is not recommended for distinguishing between benign and
      malignant adnexal masses.Frozen sections for the intraoperative diagnosis of a
      suspicious adnexal mass is recommended in settings in which availability and
      patient preference allow.  SURGICAL PROCEDURES FOR AN ADNEXAL MASS SUSPICIOUS FOR
      MALIGNANCY: To improve survival, comprehensive surgical staging with
      lymphadenectomy is recommended for the surgical management of patients with early
      stage ovarian cancer. Laparoscopy is a reasonable alternative to laparotomy,
      provided that appropriate surgery and staging can be done. The choice between
      laparoscopy and laparotomy should be based on patient and clinician preference.
      Discussion with a gynecologic oncologist is recommended. Fertility-preserving
      surgery is an acceptable alternative to more extensive surgery in patients with
      low-malignant-potential tumours and those with well-differentiated surgical stage
      i ovarian cancer. Discussion with a gynecologic oncologist is recommended.

PMID- 22876156
TI  - Excision of the primary tumour in patients with metastatic breast cancer: a
      clinical dilemma.
AB  - BACKGROUND: Approximately 10% of new breast cancer patients will present with
      overt synchronous metastatic disease. The optimal local management of those
      patients is controversial. Several series suggest that removal of the primary
      tumour is associated with a survival benefit, but the retrospective nature of
      those studies raises considerable methodologic challenges. We evaluated our
      clinical experience with the management of such patients and, more specifically,
      the impact of surgery in patients with synchronous metastasis. METHODS: We
      reviewed patients with primary breast cancer and concurrent distant metastases
      seen at our centre between 2005 and 2007. Demographic and treatment data were
      collected. Study endpoints included overall survival and symptomatic local
      progression rates. RESULTS: The 111 patients identified had a median follow-up of
      40 months (range: 0.6-71 months). We allocated the patients to one ot two groups:
      a nonsurgical group (those who did not have breast surgery, n = 63) and a
      surgical group (those who did have surgery, n = 48, 29 of whom had surgery before
      the metastatic diagnosis). When compared with patients in the nonsurgical group,
      patients in the surgical group were less likely to present with T4 tumours (23%
      vs. 35%), N3 nodal disease (8% vs. 19%), and visceral metastasis (67% vs. 73%).
      Patients in the surgical group experienced longer overall survival (49 months vs.
      33 months, p = 0.01) and lower rates of symptomatic local progression (14% vs.
      44%, p < 0.001). CONCLUSIONS: In our study, improved overall survival and
      symptomatic local control were demonstrated in the surgically treated patients;
      however, this group had less aggressive disease at presentation. The optimal
      local management of patients with metastatic breast cancer remains unknown. An
      ongoing phase iii trial, E2108, has been designed to assess the effect of breast
      surgery in metastatic patients responding to first-line systemic therapy. If
      excision of the primary tumour is associated with a survival benefit, then the
      preselected subgroup of patients who have responded to initial systemic therapy
      is the desired population in which to put this hypothesis to the test.

PMID- 22876157
TI  - Optimal prophylactic and definitive therapy for bicalutamide-induced
      gynecomastia: results of a meta-analysis.
AB  - OBJECTIVE: Bicalutamide is approved as an adjuvant to primary treatments (radical
      prostatectomy or radiotherapy) or as monotherapy in men with locally advanced,
      nonmetastatic prostate cancer (pca). However, this treatment induces gynecomastia
      in most patients, which often results in treatment discontinuation. Optimal
      therapy for these breast events is not known so far. We undertook a meta-analysis
      to assess the efficacy of various treatment options for bicalutamide-induced
      gynecomastia. METHODS: The medline, cancerlit, and Cochrane library databases
      were searched and the Google search engine was used to identify prospective and
      retrospective controlled studies published in English from January 2000 to
      December 2010 comparing prophylactic or curative treatment options with a control
      group (no treatment) for pca patients who developed bicalutamide-induced
      gynecomastia. Radiotherapy-induced cardiotoxicity was also evaluated. RESULTS:
      The search identified nine controlled trials with a total patient population of
      1573. Pooled results from prophylactic trials showed a significant reduction of
      gynecomastia in pca patients treated with prophylactic tamoxifen 20 mg daily
      (odds ratio: 0.06; 95% confidence interval: 0.05 to 0.09; p = 0.09), and pooled
      results from treatment trials showed a significant response of gynecomastia to
      definitive radiotherapy (odds ratio: 0.06; 95% confidence interval: 0.01 to 0.24;
      p < 0.0001). Aromatase inhibitors and weekly tamoxifen were not found to be
      effective as prophylactic and curative options. For the radiotherapy, skin-to
      heart distance was found to be an important risk factor for cardiotoxicity (p =
      0.006). A funnel plot of the meta-analysis showed significant heterogeneity
      (Egger test p < 0.00001) because of low sample size. CONCLUSIONS: Our meta
      analysis suggests using prophylactic tamoxifen 20 mg daily as the first-line
      preventive measure and radiotherapy as the first-line treatment option for
      bicalutamide-induced gynecomastia. Aromatase inhibitors and weekly tamoxifen are
      not recommended.

PMID- 22876158
TI  - Long-term remission after autologous stem-cell transplantation for relapsed
      histiocytic sarcoma.
AB  - Histiocytic sarcoma is diagnosed according to established criteria. However,
      treatment is controversial: although lymphoma chemotherapy regimens are often
      used, their impact on the natural history of the disease is unclear. Here, we
      report a disease-free survival of 2 years after autologous stem-cell
      transplantation in a patient with relapsed histiocytic sarcoma.

PMID- 22876159
TI  - Right atrial metastasis of uterine leiomyosarcoma causing obstructive shock.
AB  - Uterine leiomyosarcomas are rare tumours, and secondary cardiac metastases are
      even rarer. We present the case of a 56-year-old ethnic Chinese woman who was
      being treated with adjuvant pelvic radiation for uterine leiomyosarcoma when she
      presented with signs of right heart failure and shock. She was rapidly diagnosed
      with a solid mass attached to the tricuspid valve. Subsequent surgical resection
      revealed leiomyosarcoma metastasis. Metastases of uterine leiomyosarcoma to the
      heart are extremely rare, but clinicians should be aware of this phenomenon.
      Surgical resection, when feasible, can be associated with longer survival.

PMID- 22876160
TI  - Does neurologic deterioration help to differentiate between pseudoprogression and
      true disease progression in newly diagnosed glioblastoma multiforme?
AB  - Enlarging or new lesions frequently appear on magnetic resonance imaging (mri)
      after concurrent administration of radiation therapy and temozolomide in
      glioblastoma multiforme (gbm) patients. However, in nearly half such cases, the
      observed radiologic changes are not due to true disease progression, but instead
      are a result of a post-radiation inflammatory state called "pseudoprogression."
      Retrospective studies have reported that neurologic deterioration at the time of
      the post-chemoradiotherapy mri is found more commonly in patients with true
      disease progression. We report a gbm patient with both radiologic progression on
      the post-chemoradiotherapy mri and concomitant neurologic deterioration, and we
      caution against incorporating clinical deterioration into the management schema
      of patients with possible pseudoprogression.

PMID- 22876161
TI  - Occult cause of paraneoplastic acanthosis nigricans in a patient with known
      breast dcis: case and review.
AB  - Paraneoplastic acanthosis nigricans (pan) is an infrequently encountered
      cutaneous manifestation of internal malignancy. Here, we describe a case of pan
      in the setting of a known breast ductal carcinoma in situ, which, to our
      knowledge, had not been described in association with pan. As a result, thorough
      investigation was undertaken to search for another concurrent neoplasm that would
      better explain the development of pan. In so doing, we identified a coexisting
      metastatic cholangiocarcinoma. We thus conclude that when pan is observed in an
      uncommon association with a known malignancy, further investigation should be
      undertaken to explore whether a more likely occult culprit exists.

PMID- 22876162
TI  - Saponins isolated from Asparagus induce apoptosis in human hepatoma cell line
      HepG2 through a mitochondrial-mediated pathway.
AB  - OBJECTIVE: Many scientific studies have shown that Asparagus officinalis has an
      antitumour effect and enhances human immunity, but the active components and the
      antitumour mechanisms are unclear. We investigated the effects of saponins
      isolated from Asparagus on proliferation and apoptosis in the human hepatoma cell
      line HepG2. METHODS: HepG2 cells were treated with varying concentrations of
      Asparagus saponins at various times. Using mtt and flow cytometry assays, we
      evaluated the effects of Asparagus saponins on the growth and apoptosis of HepG2
      cells. Transmission electron microscopy was used to observe the morphology of
      cell apoptosis. Confocal laser scanning microscopy was used to analyze
      intracellular calcium ion concentration, mitochondrial permeability transition
      pore (mptp), and mitochondrial membrane potential (mmp). Spectrophotometry was
      applied to quantify the activity of caspase-9 and caspase-3. Flow cytometry was
      used to investigate the levels of reactive oxygen species (ros) and pH, and the
      expressions of Bcl2, Bax, CytC, and caspase-3, in HepG2 cells. RESULTS: Asparagus
      saponins inhibited the growth of HepG2 cells in a dose-dependent manner. The
      median inhibitory concentration (IC(50)) was 101.15 mg/L at 72 hours. The
      apoptosis morphology at 72 hours of treatment was obvious, showing cell
      protuberance, concentrated cytoplasm, and apoptotic bodies. The apoptotic rates
      at 72 hours were 30.9%, 51.7%, and 62.1% (for saponin concentrations of 50 mg/L,
      100 mg/L, 200 mg/L). Treatment with Asparagus saponins for 24 hours increased the
      intracellular level of ros and Ca(2+), lowered the pH, activated intracellular
      mptp, and decreased mmp in a dose-dependent manner. Treatment also increased the
      activity of caspase-9 and caspase-3, downregulated the expression of Bcl2,
      upregulated the expression of Bax, and induced release of CytC and activation of
      caspase-3. CONCLUSIONS: Asparagus saponins induce apoptosis in HepG2 cells
      through a mitochondrial-mediated and caspase-dependent pathway, suggesting that
      they may be a potent agent for the treatment of hepatocellular carcinoma.

PMID- 22876163
TI  - Oxidative dna damage of lymphocytes in peripheral blood and ascites in cancer
      patients.
AB  - BACKGROUND: Patients with malignant ascites (ma) usually experience poor quality
      of life, and treatment of this symptom remains a challenge. Oxidative stress,
      which can cause oxidative damage to dna, plays a pivotal role in carcinogenesis;
      however, the relationship between oxidative stress and dna damage to tumour
      associated lymphocytes (tals) in ma is unclear. METHODS: We measured the total
      antioxidant capacity (tac) of plasma and ma supernatant in 31 cancer patients
      with ma, and we used a comet assay to assess dna damage to both peripheral blood
      mononuclear cells (pbmcs) and tals. Measurements in age- and sex-matched healthy
      volunteers were used as controls. RESULTS: The tac of plasma was remarkably lower
      in cancer patients (9.73 +/- 1.96 U/mL) than in healthy control subjects (11.31
      +/- 1.50 U/mL, p < 0.001). The tac of ma supernatant (6.34 +/- 1.57 U/mL) was
      significantly lower than that of plasma in cancer patients (7.42 +/- 1.36 U/mL, p
      < 0.001). The comet percentage of pbmcs was higher in cancer patients (17.26% +/-
      6.04%) than in healthy control subjects (9.44% +/- 4.47%, p < 0.01). In cancer
      patients, the comet percentage of tals (36.14% +/- 17.85%) was significantly
      higher than that of pbmcs (17.26% +/- 6.04%, p < 0.001). In cancer patients with
      ma, negative correlations were observed between plasma tac and dna damage to
      pbmcs (r = -0.505, p = 0.004) and between the tac of ma supernatant and the comet
      percentage of tals (r = -0.588, p = 0.001). CONCLUSIONS: Results indicate the
      presence of significant oxidative damage to the dna of lymphocytes in peripheral
      blood and ascites from patients with ma, being especially higher in the cells
      from ascites. The lower tac of ma supernatant may be related to a higher degree
      of dna damage to tals. The present study suggests that an oxidant-antioxidant
      imbalance may be one of the mechanisms leading to the dna damage detected in
      peripheral blood and local tals in patients with ma, which may provide a novel
      approach to the treatment of ma.

PMID- 22876164
TI  - Expression of lysophosphatidic acid receptors and local invasiveness and
      metastasis in Chinese pancreatic cancers.
AB  - BACKGROUND AND OBJECTIVES: The present study evaluated the potential role of
      lysophosphatidic acid receptors (lpars) in processes leading to local
      invasiveness and metastasis in Chinese pancreatic carcinoma. METHODS: Real-time
      reverse-transcriptase polymerase chain reaction and Western blot analysis were
      used to detect expression of lpars in tumour and adjacent non-tumour tissues from
      patients with surgically resected pancreatic carcinoma. Surgical specimens from
      50 patients were examined for relative expression of each receptor's messenger
      rna (mrna) and protein. Findings were analyzed for correlations with tumour size,
      pathologic classification, clinical stage, and infiltration of capsule and
      lymphonodi. RESULTS: Increased levels of mrna of lpars (lpar1 ~ lpar3 < lpar2)
      were found in the pancreatic cancer tissues examined. Low levels of transcripts
      for lpar1, lpar2, and lpar3 receptors were detectable in adjacent non-tumour
      tissues. The difference in lpar1 protein expression between tumour and adjacent
      non-tumour tissues does not seem significant, but the signals of lpar2 expression
      in pancreatic cancer tumour tissues were significantly amplified compared with
      those in adjacent non-tumour tissues. Tumour and adjacent non-tumour tissues both
      weakly expressed lpar3 protein with no statistical difference. However,
      expression of lpar1, lpar2, and lpar3 showed an obvious correlation with
      infiltration of capsule cells, surrounding lymphonodi, and specific
      histopathologic features. CONCLUSIONS: Lysophosphatidic acid receptor is a
      promising indicator for pancreatic cancer, and our findings suggested that lpar2
      might be a potential target for clinical treatment of pancreatic cancer.

PMID- 22876165
TI  - Combined performance of physical examination, mammography, and ultrasonography
      for breast cancer screening among Chinese women: a follow-up study.
AB  - OBJECTIVE: We aimed to determine which combination of physical examination (pe),
      mammography (mam), and ultrasonography (us) would optimize breast cancer
      detection in China. METHODS: We conducted a trial of screening with pe, mam, and
      us among Chinese women 25 years of age and older. All initial screenings using
      the three modalities were completed within 30 days of each other, and subjects
      were followed approximately 1 year later. The performances of the three screening
      methods used alone, in parallel, or in series were compared. Data were analyzed
      using exact confidence intervals (cis) and the McNemar test. RESULTS: Between
      March 2009 and July 2011, 3028 eligible women completed all study examinations.
      At a mean follow-up of 1.3 years, 33 breast cancers were identified in the study
      population. Mammography detected 28 cancers; us, 24 cancers; and pe, 22 cancers.
      During the follow-up period, 2 false-negative cases occurred clinically. The
      highest sensitivity for breast cancer screening (93.9%) was achieved by
      paralleling mam with us, but came at the cost of a higher recall rate (12.15%).
      Using us alone at the first stage, followed by mam when indicated, offered high
      specificity (99.4%) and the lowest recall rate (1.82%), which were not reached at
      the expense of sensitivity (84.8%). Used in series, us and mam achieved a
      sensitivity similar to that for the same modalities used in parallel (McNemar p >
      0.05). CONCLUSIONS: Taking limited health resources into consideration, the
      strategy of screening with us alone at the first stage, followed by mam when
      indicated, may optimize breast cancer detection in most regions of China.

PMID- 22876166
TI  - Asymmetric Methods for the Synthesis of Flavanones, Chromanones, and
      Azaflavanones.
AB  - Flavanones, chromanones, and related structures are privileged natural products
      that display a wide variety of biological activities. Although flavanoids are
      abundant in nature, there are a limited number of available general and efficient
      synthetic methods for accessing molecules of this class in a stereoselective
      manner. Their structurally simple architectures belie the difficulties involved
      in installation and maintenance of the stereogenic configuration at the C2
      position, which can be sensitive and can undergo epimerization under mildly
      acidic, basic, and thermal reaction conditions. This review presents the methods
      currently used to access these related structures. The synthetic methods include
      manipulation of the flavone/flavanone core, carbon-carbon bond formation, and
      carbon-heteroatom bond formation.

PMID- 22876167
TI  - Interplay between the localization and kinetics of phosphorylation in flagellar
      pole development of the bacterium Caulobacter crescentus.
AB  - Bacterial cells maintain sophisticated levels of intracellular organization that
      allow for signal amplification, response to stimuli, cell division, and many
      other critical processes. The mechanisms underlying localization and their
      contribution to fitness have been difficult to uncover, due to the often
      challenging task of creating mutants with systematically perturbed localization
      but normal enzymatic activity, and the lack of quantitative models through which
      to interpret subtle phenotypic changes. Focusing on the model bacterium
      Caulobacter crescentus, which generates two different types of daughter cells
      from an underlying asymmetric distribution of protein phosphorylation, we use
      mathematical modeling to investigate the contribution of the localization of
      histidine kinases to the establishment of cellular asymmetry and subsequent
      developmental outcomes. We use existing mutant phenotypes and fluorescence data
      to parameterize a reaction-diffusion model of the kinases PleC and DivJ and their
      cognate response regulator DivK. We then present a systematic computational
      analysis of the effects of changes in protein localization and abundance to
      determine whether PleC localization is required for correct developmental timing
      in Caulobacter. Our model predicts the developmental phenotypes of several
      localization mutants, and suggests that a novel strain with co-localization of
      PleC and DivJ could provide quantitative insight into the signaling threshold
      required for flagellar pole development. Our analysis indicates that normal
      development can be maintained through a wide range of localization phenotypes,
      and that developmental defects due to changes in PleC localization can be rescued
      by increased PleC expression. We also show that the system is remarkably robust
      to perturbation of the kinetic parameters, and while the localization of either
      PleC or DivJ is required for asymmetric development, the delocalization of one of
      these two components does not prevent flagellar pole development. We further find
      that allosteric regulation of PleC observed in vitro does not affect the
      predicted in vivo developmental phenotypes. Taken together, our model suggests
      that cells can tolerate perturbations to localization phenotypes, whose
      evolutionary origins may be connected with reducing protein expression or with
      decoupling pre- and post-division phenotypes.

PMID- 22876168
TI  - Mutation induced extinction in finite populations: lethal mutagenesis and lethal
      isolation.
AB  - Reproduction is inherently risky, in part because genomic replication can
      introduce new mutations that are usually deleterious toward fitness. This risk is
      especially severe for organisms whose genomes replicate "semi-conservatively,"
      e.g. viruses and bacteria, where no master copy of the genome is preserved.
      Lethal mutagenesis refers to extinction of populations due to an unbearably high
      mutation rate (U), and is important both theoretically and clinically, where
      drugs can extinguish pathogens by increasing their mutation rate. Previous
      theoretical models of lethal mutagenesis assume infinite population size (N).
      However, in addition to high U, small N can accelerate extinction by
      strengthening genetic drift and relaxing selection. Here, we examine how the time
      until extinction depends jointly on N and U. We first analytically compute the
      mean time until extinction (tau) in a simplistic model where all mutations are
      either lethal or neutral. The solution motivates the definition of two distinct
      regimes: a survival phase and an extinction phase, which differ dramatically in
      both how tau scales with N and in the coefficient of variation in time until
      extinction. Next, we perform stochastic population-genetics simulations on a
      realistic fitness landscape that both (i) features an epistatic distribution of
      fitness effects that agrees with experimental data on viruses and (ii) is based
      on the biophysics of protein folding. More specifically, we assume that mutations
      inflict fitness penalties proportional to the extent that they unfold proteins.
      We find that decreasing N can cause phase transition-like behavior from survival
      to extinction, which motivates the concept of "lethal isolation." Furthermore, we
      find that lethal mutagenesis and lethal isolation interact synergistically, which
      may have clinical implications for treating infections. Broadly, we conclude that
      stably folded proteins are only possible in ecological settings that support
      sufficiently large populations.

PMID- 22876169
TI  - Molecular constraints on synaptic tagging and maintenance of long-term
      potentiation: a predictive model.
AB  - Protein synthesis-dependent, late long-term potentiation (LTP) and depression
      (LTD) at glutamatergic hippocampal synapses are well characterized examples of
      long-term synaptic plasticity. Persistent increased activity of protein kinase M
      zeta (PKMzeta) is thought essential for maintaining LTP. Additional spatial and
      temporal features that govern LTP and LTD induction are embodied in the synaptic
      tagging and capture (STC) and cross capture hypotheses. Only synapses that have
      been "tagged" by a stimulus sufficient for LTP and learning can "capture"
      PKMzeta. A model was developed to simulate the dynamics of key molecules required
      for LTP and LTD. The model concisely represents relationships between tagging,
      capture, LTD, and LTP maintenance. The model successfully simulated LTP
      maintained by persistent synaptic PKMzeta, STC, LTD, and cross capture, and makes
      testable predictions concerning the dynamics of PKMzeta. The maintenance of LTP,
      and consequently of at least some forms of long-term memory, is predicted to
      require continual positive feedback in which PKMzeta enhances its own synthesis
      only at potentiated synapses. This feedback underlies bistability in the activity
      of PKMzeta. Second, cross capture requires the induction of LTD to induce
      dendritic PKMzeta synthesis, although this may require tagging of a nearby
      synapse for LTP. The model also simulates the effects of PKMzeta inhibition, and
      makes additional predictions for the dynamics of CaM kinases. Experiments testing
      the above predictions would significantly advance the understanding of memory
      maintenance.

PMID- 22876170
TI  - Alternative protein-protein interfaces are frequent exceptions.
AB  - The intricate molecular details of protein-protein interactions (PPIs) are
      crucial for function. Therefore, measuring the same interacting protein pair
      again, we expect the same result. This work measured the similarity in the
      molecular details of interaction for the same and for homologous protein pairs
      between different experiments. All scores analyzed suggested that different
      experiments often find exceptions in the interfaces of similar PPIs: up to 22% of
      all comparisons revealed some differences even for sequence-identical pairs of
      proteins. The corresponding number for pairs of close homologs reached 68%.
      Conversely, the interfaces differed entirely for 12-29% of all comparisons. All
      these estimates were calculated after redundancy reduction. The magnitude of
      interface differences ranged from subtle to the extreme, as illustrated by a few
      examples. An extreme case was a change of the interacting domains between two
      observations of the same biological interaction. One reason for different
      interfaces was the number of copies of an interaction in the same complex: the
      probability of observing alternative binding modes increases with the number of
      copies. Even after removing the special cases with alternative hetero-interfaces
      to the same homomer, a substantial variability remained. Our results strongly
      support the surprising notion that there are many alternative solutions to make
      the intricate molecular details of PPIs crucial for function.

PMID- 22876171
TI  - Inferring dynamic signatures of microbes in complex host ecosystems.
AB  - The human gut microbiota comprise a complex and dynamic ecosystem that profoundly
      affects host development and physiology. Standard approaches for analyzing time
      series data of the microbiota involve computation of measures of ecological
      community diversity at each time-point, or measures of dissimilarity between
      pairs of time-points. Although these approaches, which treat data as static
      snapshots of microbial communities, can identify shifts in overall community
      structure, they fail to capture the dynamic properties of individual members of
      the microbiota and their contributions to the underlying time-varying behavior of
      host ecosystems. To address the limitations of current methods, we present a
      computational framework that uses continuous-time dynamical models coupled with
      Bayesian dimensionality adaptation methods to identify time-dependent signatures
      of individual microbial taxa within a host as well as across multiple hosts. We
      apply our framework to a publicly available dataset of 16S rRNA gene sequences
      from stool samples collected over ten months from multiple human subjects, each
      of whom received repeated courses of oral antibiotics. Using new diversity
      measures enabled by our framework, we discover groups of both phylogenetically
      close and distant bacterial taxa that exhibit consensus responses to antibiotic
      exposure across multiple human subjects. These consensus responses reveal a
      timeline for equilibration of sub-communities of micro-organisms with distinct
      physiologies, yielding insights into the successive changes that occur in
      microbial populations in the human gut after antibiotic treatments. Additionally,
      our framework leverages microbial signatures shared among human subjects to
      automatically design optimal experiments to interrogate dynamic properties of the
      microbiota in new studies. Overall, our approach provides a powerful, general
      purpose framework for understanding the dynamic behaviors of complex microbial
      ecosystems, which we believe will prove instrumental for future studies in this
      field.

PMID- 22876172
TI  - The role of local backrub motions in evolved and designed mutations.
AB  - Amino acid substitutions in protein structures often require subtle backbone
      adjustments that are difficult to model in atomic detail. An improved ability to
      predict realistic backbone changes in response to engineered mutations would be
      of great utility for the blossoming field of rational protein design. One model
      that has recently grown in acceptance is the backrub motion, a low-energy
      dipeptide rotation with single-peptide counter-rotations, that is coupled to
      dynamic two-state sidechain rotamer jumps, as evidenced by alternate
      conformations in very high-resolution crystal structures. It has been speculated
      that backrubs may facilitate sequence changes equally well as rotamer changes.
      However, backrub-induced shifts and experimental uncertainty are of similar
      magnitude for backbone atoms in even high-resolution structures, so comparison of
      wildtype-vs.-mutant crystal structure pairs is not sufficient to directly link
      backrubs to mutations. In this study, we use two alternative approaches that
      bypass this limitation. First, we use a quality-filtered structure database to
      aggregate many examples for precisely defined motifs with single amino acid
      differences, and find that the effectively amplified backbone differences closely
      resemble backrubs. Second, we directly apply a provably-accurate, backrub-enabled
      protein design algorithm to idealized versions of these motifs, and discover that
      the lowest-energy computed models match the average-coordinate experimental
      structures. These results support the hypothesis that backrubs participate in
      natural protein evolution and validate their continued use for design of
      synthetic proteins.

PMID- 22876173
TI  - Phagocyte responses to protozoan infection and how Toxoplasma gondii meets the
      challenge.

PMID- 22876174
TI  - Routine use of microbial whole genome sequencing in diagnostic and public health
      microbiology.

PMID- 22876175
TI  - Identification of MrtAB, an ABC transporter specifically required for Yersinia
      pseudotuberculosis to colonize the mesenteric lymph nodes.
AB  - A highly conserved virulence plasmid encoding a type III secretion system is
      shared by the three Yersinia species most pathogenic for mammals. Although
      factors encoded on this plasmid enhance the ability of Yersinia to thrive in
      their mammalian hosts, the loss of this virulence plasmid does not eliminate
      growth or survival in host organs. Most notably, yields of viable plasmid
      deficient Yersinia pseudotuberculosis (Yptb) are indistinguishable from wild-type
      Yptb within mesenteric lymph nodes. To identify chromosomal virulence factors
      that allow for plasmid-independent survival during systemic infection of mice, we
      generated transposon insertions in plasmid-deficient Yptb, and screened a library
      having over 20,000 sequence-identified insertions. Among the previously
      uncharacterized loci, insertions in mrtAB, an operon encoding an ABC family
      transporter, had the most profound phenotype in a plasmid-deficient background.
      The absence of MrtAB, however, had no effect on growth in the liver and spleen of
      a wild type strain having an intact virulence plasmid, but caused a severe defect
      in colonization of the mesenteric lymph nodes. Although this result is consistent
      with lack of expression of the type III secretion system by Wt Yptb in the
      mesenteric lymph nodes, a reporter for YopE indicated that expression of the
      system was robust. We demonstrate that the ATPase activity of MrtB is required
      for growth in mice, indicating that transport activity is required for virulence.
      Indeed, MrtAB appears to function as an efflux pump, as the ATPase activity
      enhances resistance to ethidium bromide while increasing sensitivity to
      pyocyanin, consistent with export across the inner membrane.

PMID- 22876176
TI  - Structural and biochemical basis for development of influenza virus inhibitors
      targeting the PA endonuclease.
AB  - Emerging influenza viruses are a serious threat to human health because of their
      pandemic potential. A promising target for the development of novel anti
      influenza therapeutics is the PA protein, whose endonuclease activity is
      essential for viral replication. Translation of viral mRNAs by the host ribosome
      requires mRNA capping for recognition and binding, and the necessary mRNA caps
      are cleaved or "snatched" from host pre-mRNAs by the PA endonuclease. The
      structure-based development of inhibitors that target PA endonuclease is now
      possible with the recent crystal structure of the PA catalytic domain. In this
      study, we sought to understand the molecular mechanism of inhibition by several
      compounds that are known or predicted to block endonuclease-dependent polymerase
      activity. Using an in vitro endonuclease activity assay, we show that these
      compounds block the enzymatic activity of the isolated PA endonuclease domain.
      Using X-ray crystallography, we show how these inhibitors coordinate the two
      metal endonuclease active site and engage the active site residues. Two
      structures also reveal an induced-fit mode of inhibitor binding. The structures
      allow a molecular understanding of the structure-activity relationship of several
      known influenza inhibitors and the mechanism of drug resistance by a PA mutation.
      Taken together, our data reveal new strategies for structure-based design and
      optimization of PA endonuclease inhibitors.

PMID- 22876177
TI  - Structural analysis of specific metal chelating inhibitor binding to the
      endonuclease domain of influenza pH1N1 (2009) polymerase.
AB  - It is generally recognised that novel antiviral drugs, less prone to resistance,
      would be a desirable alternative to current drug options in order to be able to
      treat potentially serious influenza infections. The viral polymerase, which
      performs transcription and replication of the RNA genome, is an attractive target
      for antiviral drugs since potent polymerase inhibitors could directly stop viral
      replication at an early stage. Recent structural studies on functional domains of
      the heterotrimeric polymerase, which comprises subunits PA, PB1 and PB2, open the
      way to a structure based approach to optimise inhibitors of viral replication. In
      particular, the unique cap-snatching mechanism of viral transcription can be
      inhibited by targeting either the PB2 cap-binding or PA endonuclease domains.
      Here we describe high resolution X-ray co-crystal structures of the 2009 pandemic
      H1N1 (pH1N1) PA endonuclease domain with a series of specific inhibitors,
      including four diketo compounds and a green tea catechin, all of which chelate
      the two critical manganese ions in the active site of the enzyme. Comparison of
      the binding mode of the different compounds and that of a mononucleotide
      phosphate highlights, firstly, how different substituent groups on the basic
      metal binding scaffold can be orientated to bind in distinct sub-pockets within
      the active site cavity, and secondly, the plasticity of certain structural
      elements of the active site cavity, which result in induced fit binding. These
      results will be important in optimising the design of more potent inhibitors
      targeting the cap-snatching endonuclease activity of influenza virus polymerase.

PMID- 22876178
TI  - AsrR is an oxidative stress sensing regulator modulating Enterococcus faecium
      opportunistic traits, antimicrobial resistance, and pathogenicity.
AB  - Oxidative stress serves as an important host/environmental signal that triggers a
      wide range of responses in microorganisms. Here, we identified an oxidative
      stress sensor and response regulator in the important multidrug-resistant
      nosocomial pathogen Enterococcus faecium belonging to the MarR family and called
      AsrR (antibiotic and stress response regulator). The AsrR regulator used cysteine
      oxidation to sense the hydrogen peroxide which results in its dissociation to
      promoter DNA. Transcriptome analysis showed that the AsrR regulon was composed of
      181 genes, including representing functionally diverse groups involved in
      pathogenesis, antibiotic and antimicrobial peptide resistance, oxidative stress,
      and adaptive responses. Consistent with the upregulated expression of the pbp5
      gene, encoding a low-affinity penicillin-binding protein, the asrR null mutant
      was found to be more resistant to beta-lactam antibiotics. Deletion of asrR
      markedly decreased the bactericidal activity of ampicillin and vancomycin, which
      are both commonly used to treat infections due to enterococci, and also led to
      over-expression of two major adhesins, acm and ecbA, which resulted in enhanced
      in vitro adhesion to human intestinal cells. Additional pathogenic traits were
      also reinforced in the asrR null mutant including greater capacity than the
      parental strain to form biofilm in vitro and greater persistance in Galleria
      mellonella colonization and mouse systemic infection models. Despite
      overexpression of oxidative stress-response genes, deletion of asrR was
      associated with a decreased oxidative stress resistance in vitro, which
      correlated with a reduced resistance to phagocytic killing by murine macrophages.
      Interestingly, both strains showed similar amounts of intracellular reactive
      oxygen species. Finally, we observed a mutator phenotype and enhanced DNA
      transfer frequencies in the asrR deleted strain. These data indicate that AsrR
      plays a major role in antimicrobial resistance and adaptation for survival within
      the host, thereby contributes importantly to the opportunistic traits of E.
      faecium.

PMID- 22876179
TI  - Small protease sensitive oligomers of PrPSc in distinct human prions determine
      conversion rate of PrP(C).
AB  - The mammalian prions replicate by converting cellular prion protein (PrP(C)) into
      pathogenic conformational isoform (PrP(Sc)). Variations in prions, which cause
      different disease phenotypes, are referred to as strains. The mechanism of high
      fidelity replication of prion strains in the absence of nucleic acid remains
      unsolved. We investigated the impact of different conformational characteristics
      of PrP(Sc) on conversion of PrP(C) in vitro using PrP(Sc) seeds from the most
      frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD). The
      conversion potency of a broad spectrum of distinct sCJD prions was governed by
      the level, conformation, and stability of small oligomers of the protease
      sensitive (s) PrP(Sc). The smallest most potent prions present in sCJD brains
      were composed only of~20 monomers of PrP(Sc). The tight correlation between
      conversion potency of small oligomers of human sPrP(Sc) observed in vitro and
      duration of the disease suggests that sPrP(Sc) conformers are an important
      determinant of prion strain characteristics that control the progression rate of
      the disease.

PMID- 22876180
TI  - Natural transformation facilitates transfer of transposons, integrons and gene
      cassettes between bacterial species.
AB  - We have investigated to what extent natural transformation acting on free DNA
      substrates can facilitate transfer of mobile elements including transposons,
      integrons and/or gene cassettes between bacterial species. Naturally
      transformable cells of Acinetobacter baylyi were exposed to DNA from integron
      carrying strains of the genera Acinetobacter, Citrobacter, Enterobacter,
      Escherichia, Pseudomonas, and Salmonella to determine the nature and frequency of
      transfer. Exposure to the various DNA sources resulted in acquisition of
      antibiotic resistance traits as well as entire integrons and transposons, over a
      24 h exposure period. DNA incorporation was not solely dependent on integrase
      functions or the genetic relatedness between species. DNA sequence analyses
      revealed that several mechanisms facilitated stable integration in the recipient
      genome depending on the nature of the donor DNA; homologous or heterologous
      recombination and various types of transposition (Tn21-like and IS26-like). Both
      donor strains and transformed isolates were extensively characterized by
      antimicrobial susceptibility testing, integron- and cassette-specific PCRs, DNA
      sequencing, pulsed field gel electrophoreses (PFGE), Southern blot
      hybridizations, and by re-transformation assays. Two transformant strains were
      also genome-sequenced. Our data demonstrate that natural transformation
      facilitates interspecies transfer of genetic elements, suggesting that the
      transient presence of DNA in the cytoplasm may be sufficient for genomic
      integration to occur. Our study provides a plausible explanation for why sequence
      conserved transposons, IS elements and integrons can be found disseminated among
      bacterial species. Moreover, natural transformation of integron harboring
      populations of competent bacteria revealed that interspecies exchange of gene
      cassettes can be highly efficient, and independent on genetic relatedness between
      donor and recipient. In conclusion, natural transformation provides a much
      broader capacity for horizontal acquisitions of genetic elements and hence,
      resistance traits from divergent species than previously assumed.

PMID- 22876181
TI  - CPAF: a Chlamydial protease in search of an authentic substrate.
AB  - Bacteria in the genus Chlamydia are major human pathogens that cause an
      intracellular infection. A chlamydial protease, CPAF, has been proposed as an
      important virulence factor that cleaves or degrades at least 16 host proteins,
      thereby altering multiple cellular processes. We examined 11 published CPAF
      substrates and found that there was no detectable proteolysis when CPAF activity
      was inhibited during cell processing. We show that the reported proteolysis of
      these putative CPAF substrates was due to enzymatic activity in cell lysates
      rather than in intact cells. Nevertheless, Chlamydia-infected cells displayed
      Chlamydia-host interactions, such as Golgi reorganization, apoptosis resistance,
      and host cytoskeletal remodeling, that have been attributed to CPAF-dependent
      proteolysis of host proteins. Our findings suggest that other mechanisms may be
      responsible for these Chlamydia-host interactions, and raise concerns about all
      published CPAF substrates and the proposed roles of CPAF in chlamydial
      pathogenesis.

PMID- 22876182
TI  - Bap, a biofilm matrix protein of Staphylococcus aureus prevents cellular
      internalization through binding to GP96 host receptor.
AB  - The biofilm matrix, composed of exopolysaccharides, proteins, nucleic acids and
      lipids, plays a well-known role as a defence structure, protecting bacteria from
      the host immune system and antimicrobial therapy. However, little is known about
      its responsibility in the interaction of biofilm cells with host tissues.
      Staphylococcus aureus, a leading cause of biofilm-associated chronic infections,
      is able to develop a biofilm built on a proteinaceous Bap-mediated matrix. Here,
      we used the Bap protein as a model to investigate the role that components of the
      biofilm matrix play in the interaction of S. aureus with host cells. The results
      show that Bap promotes the adhesion but prevents the entry of S. aureus into
      epithelial cells. A broad analysis of potential interaction partners for Bap
      using ligand overlayer immunoblotting, immunoprecipitation with purified Bap and
      pull down with intact bacteria, identified a direct binding between Bap and
      Gp96/GRP94/Hsp90 protein. The interaction of Bap with Gp96 provokes a significant
      reduction in the capacity of S. aureus to invade epithelial cells by interfering
      with the fibronectin binding protein invasion pathway. Consistent with these
      results, Bap deficient bacteria displayed an enhanced capacity to invade mammary
      gland epithelial cells in a lactating mice mastitis model. Our observations begin
      to elucidate the mechanisms by which components of the biofilm matrix can
      facilitate the colonization of host tissues and the establishment of persistent
      infections.

PMID- 22876183
TI  - High virulence of Wolbachia after host switching: when autophagy hurts.
AB  - Wolbachia are widespread endosymbionts found in a large variety of arthropods.
      While these bacteria are generally transmitted vertically and exhibit weak
      virulence in their native hosts, a growing number of studies suggests that
      horizontal transfers of Wolbachia to new host species also occur frequently in
      nature. In transfer situations, virulence variations can be predicted since hosts
      and symbionts are not adapted to each other. Here, we describe a situation where
      a Wolbachia strain (wVulC) becomes a pathogen when transfected from its native
      terrestrial isopod host species (Armadillidium vulgare) to another species
      (Porcellio d. dilatatus). Such transfer of wVulC kills all recipient animals
      within 75 days. Before death, animals suffer symptoms such as growth slowdown and
      nervous system disorders. Neither those symptoms nor mortalities were observed
      after injection of wVulC into its native host A. vulgare. Analyses of wVulC's
      densities in main organs including Central Nervous System (CNS) of both naturally
      infected A. vulgare and transfected P. d. dilatatus and A. vulgare individuals
      revealed a similar pattern of host colonization suggesting an overall similar
      resistance of both host species towards this bacterium. However, for only P. d.
      dilatatus, we observed drastic accumulations of autophagic vesicles and vacuoles
      in the nerve cells and adipocytes of the CNS from individuals infected by wVulC.
      The symptoms and mortalities could therefore be explained by this huge autophagic
      response against wVulC in P. d. dilatatus cells that is not triggered in A.
      vulgare. Our results show that Wolbachia (wVulC) can lead to a pathogenic
      interaction when transferred horizontally into species that are phylogenetically
      close to their native hosts. This change in virulence likely results from the
      autophagic response of the host, strongly altering its tolerance to the symbiont
      and turning it into a deadly pathogen.

PMID- 22876184
TI  - IL-10 suppression of NK/DC crosstalk leads to poor priming of MCMV-specific CD4 T
      cells and prolonged MCMV persistence.
AB  - IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity
      to infection by exerting suppressive effects on different cell types. Herpes
      viruses induce IL-10 to modulate the virus-host balance towards their own
      benefit, resulting in prolonged virus persistence. To define the cellular and
      molecular players involved in IL-10 modulation of herpes virus-specific immunity,
      we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10
      specifically curtails the MCMV-specific CD4 T cell response by suppressing the
      bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In
      absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T
      cells and we defined the pro-inflammatory cytokines IL-12, IFN-gamma and TNF
      alpha as well as NK cell activating receptors NKG2D and NCR-1 to regulate this
      bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV
      specific CD4 T cells in Il10(-/-) mice led to faster control of lytic viral
      replication, but this came at the expense of TNF-alpha mediated immunopathology.
      Taken together, our data show that early induction of IL-10 during MCMV infection
      critically regulates the strength of the innate-adaptive immune cell crosstalk,
      thereby impacting beneficially on the ensuing virus-host balance for both the
      virus and the host.

PMID- 22876185
TI  - The Ebola virus glycoprotein contributes to but is not sufficient for virulence
      in vivo.
AB  - Among the Ebola viruses most species cause severe hemorrhagic fever in humans;
      however, Reston ebolavirus (REBOV) has not been associated with human disease
      despite numerous documented infections. While the molecular basis for this
      difference remains unclear, in vitro evidence has suggested a role for the
      glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence
      for such a role in the context of virus infection has been notably lacking. In
      order to assess the role of GP in EBOV virulence, we have developed a novel
      reverse genetics system for REBOV, which we report here. Together with a
      previously published full-length clone for Zaire ebolavirus (ZEBOV), this
      provides a unique possibility to directly investigate the role of an entire
      filovirus protein in pathogenesis. To this end we have generated recombinant
      ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the
      glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and
      rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated
      with kinetics similar to their parent virus in tissue culture, indicating that
      the exchange of GP in these chimeric viruses is well tolerated. However, in a
      mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and
      prolonged time to death when compared to rZEBOV, confirming that GP does indeed
      contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP
      did not show any signs of virulence, and was in fact slightly attenuated compared
      to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal
      phenotype or exacerbate disease in this model. Thus, while these findings provide
      direct evidence that GP contributes to filovirus virulence in vivo, they also
      clearly indicate that other factors are needed for the acquisition of full
      virulence.

PMID- 22876186
TI  - A Candida biofilm-induced pathway for matrix glucan delivery: implications for
      drug resistance.
AB  - Extracellular polysaccharides are key constituents of the biofilm matrix of many
      microorganisms. One critical carbohydrate component of Candida albicans biofilms,
      beta-1,3 glucan, has been linked to biofilm protection from antifungal agents. In
      this study, we identify three glucan modification enzymes that function to
      deliver glucan from the cell to the extracellular matrix. These enzymes include
      two predicted glucan transferases and an exo-glucanase, encoded by BGL2, PHR1,
      and XOG1, respectively. We show that the enzymes are crucial for both delivery of
      beta-1,3 glucan to the biofilm matrix and for accumulation of mature matrix
      biomass. The enzymes do not appear to impact cell wall glucan content of biofilm
      cells, nor are they necessary for filamentation or biofilm formation. We
      demonstrate that mutants lacking these genes exhibit enhanced susceptibility to
      the commonly used antifungal, fluconazole, during biofilm growth only.
      Transcriptional analysis and biofilm phenotypes of strains with multiple
      mutations suggest that these enzymes act in a complementary fashion to distribute
      matrix downstream of the primary beta-1,3 glucan synthase encoded by FKS1.
      Furthermore, our observations suggest that this matrix delivery pathway works
      independently from the C. albicans ZAP1 matrix formation regulatory pathway.
      These glucan modification enzymes appear to play a biofilm-specific role in
      mediating the delivery and organization of mature biofilm matrix. We propose that
      the discovery of inhibitors for these enzymes would provide promising anti
      biofilm therapeutics.

PMID- 22876187
TI  - Structural bases of coronavirus attachment to host aminopeptidase N and its
      inhibition by neutralizing antibodies.
AB  - The coronaviruses (CoVs) are enveloped viruses of animals and humans associated
      mostly with enteric and respiratory diseases, such as the severe acute
      respiratory syndrome and 10-20% of all common colds. A subset of CoVs uses the
      cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell
      entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates
      the attachment of the virus particles to APN and subsequent cell entry, which can
      be blocked by neutralizing antibodies. Here we describe the crystal structures of
      the receptor-binding domains (RBDs) of two closely related CoV strains,
      transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in
      complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody.
      The data provide detailed information on the architecture of the dimeric pAPN
      ectodomain and its interaction with the CoV S. We show that a protruding receptor
      binding edge in the S determines virus-binding specificity for recessed glycan
      containing surfaces in the membrane-distal region of the pAPN ectodomain.
      Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests
      that the conformation of the S receptor-binding region determines cell entry
      receptor specificity. Moreover, the receptor-binding edge is a major antigenic
      determinant in the TGEV envelope S that is targeted by neutralizing antibodies.
      Our results provide a compelling view on CoV cell entry and immune
      neutralization, and may aid the design of antivirals or CoV vaccines. APN is also
      considered a target for cancer therapy and its structure, reported here, could
      facilitate the development of anti-cancer drugs.

PMID- 22876188
TI  - Exon level transcriptomic profiling of HIV-1-infected CD4(+) T cells reveals
      virus-induced genes and host environment favorable for viral replication.
AB  - HIV-1 is extremely specialized since, even amongst CD4(+) T lymphocytes (its
      major natural reservoir in peripheral blood), the virus productively infects only
      a small proportion of cells under an activated state. As the percentage of HIV-1
      infected cells is very low, most studies have so far failed to capture the
      precise transcriptomic profile at the whole-genome scale of cells highly
      susceptible to virus infection. Using Affymetrix Exon array technology and a
      reporter virus allowing the magnetic isolation of HIV-1-infected cells, we
      describe the host cell factors most favorable for virus establishment and
      replication along with an overview of virus-induced changes in host gene
      expression occurring exclusively in target cells productively infected with HIV
      1. We also establish that within a population of activated CD4(+) T cells, HIV-1
      has no detectable effect on the transcriptome of uninfected bystander cells at
      early time points following infection. The data gathered in this study provides
      unique insights into the biology of HIV-1-infected CD4(+) T cells and identifies
      genes thought to play a determinant role in the interplay between the virus and
      its host. Furthermore, it provides the first catalogue of alternative splicing
      events found in primary human CD4(+) T cells productively infected with HIV-1.

PMID- 22876189
TI  - The metabochip, a custom genotyping array for genetic studies of metabolic,
      cardiovascular, and anthropometric traits.
AB  - Genome-wide association studies have identified hundreds of loci for type 2
      diabetes, coronary artery disease and myocardial infarction, as well as for
      related traits such as body mass index, glucose and insulin levels, lipid levels,
      and blood pressure. These studies also have pointed to thousands of loci with
      promising but not yet compelling association evidence. To establish association
      at additional loci and to characterize the genome-wide significant loci by fine
      mapping, we designed the "Metabochip," a custom genotyping array that assays
      nearly 200,000 SNP markers. Here, we describe the Metabochip and its component
      SNP sets, evaluate its performance in capturing variation across the allele
      frequency spectrum, describe solutions to methodological challenges commonly
      encountered in its analysis, and evaluate its performance as a platform for
      genotype imputation. The metabochip achieves dramatic cost efficiencies compared
      to designing single-trait follow-up reagents, and provides the opportunity to
      compare results across a range of related traits. The metabochip and similar
      custom genotyping arrays offer a powerful and cost-effective approach to follow
      up large-scale genotyping and sequencing studies and advance our understanding of
      the genetic basis of complex human diseases and traits.

PMID- 22876191
TI  - Inheritance beyond plain heritability: variance-controlling genes in Arabidopsis
      thaliana.
AB  - The phenotypic effect of a gene is normally described by the mean-difference
      between alternative genotypes. A gene may, however, also influence the phenotype
      by causing a difference in variance between genotypes. Here, we reanalyze a
      publicly available Arabidopsis thaliana dataset [1] and show that genetic
      variance heterogeneity appears to be as common as normal additive effects on a
      genomewide scale. The study also develops theory to estimate the contributions of
      variance differences between genotypes to the phenotypic variance, and this is
      used to show that individual loci can explain more than 20% of the phenotypic
      variance. Two well-studied systems, cellular control of molybdenum level by the
      ion-transporter MOT1 and flowering-time regulation by the FRI-FLC expression
      network, and a novel association for Leaf serration are used to illustrate the
      contribution of major individual loci, expression pathways, and gene-by
      environment interactions to the genetic variance heterogeneity.

PMID- 22876190
TI  - A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B
      ubiquitylation to regulate transcript elongation in fission yeast.
AB  - Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved
      patterns of histone modification. Whereas histone modifications have established
      roles in transcription initiation, their functions during elongation are not
      understood. Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in
      coordinating co-transcriptional histone modification by promoting site-specific
      methylation of histone H3. H2Bub1 also regulates gene expression through an
      unidentified, methylation-independent mechanism. Here we reveal bidirectional
      communication between H2Bub1 and Cdk9, the ortholog of metazoan positive
      transcription elongation factor b (P-TEFb), in the fission yeast
      Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that
      lowering Cdk9 activity or preventing phosphorylation of its substrate, the
      transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely,
      mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease
      Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined
      with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies
      morphologic and growth defects due to H2Bub1 loss, suggesting independent,
      partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly,
      mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity
      requirement in vivo, and cdk9 mutations suppress cell-morphology defects in
      H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation
      also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of
      transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5
      phosphorylation indicates positive feedback, mutual suppression by cdk9 and
      H2Bub1-pathway mutations suggests antagonistic functions that must be kept in
      balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to
      deranged gene expression and aberrant cell morphologies, revealing a novel
      function of a conserved, co-transcriptional histone modification.

PMID- 22876192
TI  - Epigenetic remodeling of meiotic crossover frequency in Arabidopsis thaliana DNA
      methyltransferase mutants.
AB  - Meiosis is a specialized eukaryotic cell division that generates haploid gametes
      required for sexual reproduction. During meiosis, homologous chromosomes pair and
      undergo reciprocal genetic exchange, termed crossover (CO). Meiotic CO frequency
      varies along the physical length of chromosomes and is determined by hierarchical
      mechanisms, including epigenetic organization, for example methylation of the DNA
      and histones. Here we investigate the role of DNA methylation in determining
      patterns of CO frequency along Arabidopsis thaliana chromosomes. In A. thaliana
      the pericentromeric regions are repetitive, densely DNA methylated, and
      suppressed for both RNA polymerase-II transcription and CO frequency. DNA
      hypomethylated methyltransferase1 (met1) mutants show transcriptional
      reactivation of repetitive sequences in the pericentromeres, which we demonstrate
      is coupled to extensive remodeling of CO frequency. We observe elevated
      centromere-proximal COs in met1, coincident with pericentromeric decreases and
      distal increases. Importantly, total numbers of CO events are similar between
      wild type and met1, suggesting a role for interference and homeostasis in CO
      remodeling. To understand recombination distributions at a finer scale we
      generated CO frequency maps close to the telomere of chromosome 3 in wild type
      and demonstrate an elevated recombination topology in met1. Using a pollen-typing
      strategy we have identified an intergenic nucleosome-free CO hotspot 3a, and we
      demonstrate that it undergoes increased recombination activity in met1. We
      hypothesize that modulation of 3a activity is caused by CO remodeling driven by
      elevated centromeric COs. These data demonstrate how regional epigenetic
      organization can pattern recombination frequency along eukaryotic chromosomes.

PMID- 22876193
TI  - Variation of BMP3 contributes to dog breed skull diversity.
AB  - Since the beginnings of domestication, the craniofacial architecture of the
      domestic dog has morphed and radiated to human whims. By beginning to define the
      genetic underpinnings of breed skull shapes, we can elucidate mechanisms of
      morphological diversification while presenting a framework for understanding
      human cephalic disorders. Using intrabreed association mapping with museum
      specimen measurements, we show that skull shape is regulated by at least five
      quantitative trait loci (QTLs). Our detailed analysis using whole-genome
      sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish
      show that Bmp3 function in cranial development is ancient. Our study reveals the
      causal variant for a canine QTL contributing to a major morphologic trait.

PMID- 22876194
TI  - A luminal glycoprotein drives dose-dependent diameter expansion of the Drosophila
      melanogaster hindgut tube.
AB  - An important step in epithelial organ development is size maturation of the organ
      lumen to attain correct dimensions. Here we show that the regulated expression of
      Tenectin (Tnc) is critical to shape the Drosophila melanogaster hindgut tube. Tnc
      is a secreted protein that fills the embryonic hindgut lumen during tube diameter
      expansion. Inside the lumen, Tnc contributes to detectable O-Glycans and forms a
      dense striated matrix. Loss of tnc causes a narrow hindgut tube, while Tnc over
      expression drives tube dilation in a dose-dependent manner. Cellular analyses
      show that luminal accumulation of Tnc causes an increase in inner and outer tube
      diameter, and cell flattening within the tube wall, similar to the effects of a
      hydrostatic pressure in other systems. When Tnc expression is induced only in
      cells at one side of the tube wall, Tnc fills the lumen and equally affects all
      cells at the lumen perimeter, arguing that Tnc acts non-cell-autonomously.
      Moreover, when Tnc expression is directed to a segment of a tube, its luminal
      accumulation is restricted to this segment and affects the surrounding cells to
      promote a corresponding local diameter expansion. These findings suggest that
      deposition of Tnc into the lumen might contribute to expansion of the lumen
      volume, and thereby to stretching of the tube wall. Consistent with such an idea,
      ectopic expression of Tnc in different developing epithelial tubes is sufficient
      to cause dilation, while epidermal Tnc expression has no effect on morphology.
      Together, the results show that epithelial tube diameter can be modelled by
      regulating the levels and pattern of expression of a single luminal glycoprotein.

PMID- 22876195
TI  - Human developmental enhancers conserved between deuterostomes and protostomes.
AB  - The identification of homologies, whether morphological, molecular, or genetic,
      is fundamental to our understanding of common biological principles. Homologies
      bridging the great divide between deuterostomes and protostomes have served as
      the basis for current models of animal evolution and development. It is now
      appreciated that these two clades share a common developmental toolkit consisting
      of conserved transcription factors and signaling pathways. These patterning genes
      sometimes show common expression patterns and genetic interactions, suggesting
      the existence of similar or even conserved regulatory apparatus. However,
      previous studies have found no regulatory sequence conserved between
      deuterostomes and protostomes. Here we describe the first such enhancers, which
      we call bilaterian conserved regulatory elements (Bicores). Bicores show
      conservation of sequence and gene synteny. Sequence conservation of Bicores
      reflects conserved patterns of transcription factor binding sites. We predict
      that Bicores act as response elements to signaling pathways, and we show that
      Bicores are developmental enhancers that drive expression of transcriptional
      repressors in the vertebrate central nervous system. Although the small number of
      identified Bicores suggests extensive rewiring of cis-regulation between the
      protostome and deuterostome clades, additional Bicores may be revealed as our
      understanding of cis-regulatory logic and sample of bilaterian genomes continue
      to grow.

PMID- 22876196
TI  - Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in
      Drosophila and mammals.
AB  - Feeding behavior is one of the most essential activities in animals, which is
      tightly regulated by neuroendocrine factors. Drosophila melanogaster short
      neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY)
      regulate food intake. Understanding the molecular mechanism of sNPF and NPY
      signaling is critical to elucidate feeding regulation. Here, we found that
      minibrain (mnb) and the mammalian ortholog Dyrk1a, target genes of sNPF and NPY
      signaling, [corrected] regulate food intake in Drosophila melanogaster and mice.
      In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and
      NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway.
      Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which
      potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake.
      Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY
      expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a
      transgenic mice exhibited decreased FOXO acetylation and increased NPY expression
      in the hypothalamus, and [corrected] increased food intake. Our findings
      demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary
      conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.

PMID- 22876197
TI  - Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes
      that determine bone strength.
AB  - Osteoporosis is a common polygenic disease and global healthcare priority but its
      genetic basis remains largely unknown. We report a high-throughput multi
      parameter phenotype screen to identify functionally significant skeletal
      phenotypes in mice generated by the Wellcome Trust Sanger Institute Mouse
      Genetics Project and discover novel genes that may be involved in the
      pathogenesis of osteoporosis. The integrated use of primary phenotype data with
      quantitative x-ray microradiography, micro-computed tomography, statistical
      approaches and biomechanical testing in 100 unselected knockout mouse strains
      identified nine new genetic determinants of bone mass and strength. These nine
      new genes include five whose deletion results in low bone mass and four whose
      deletion results in high bone mass. None of the nine genes have been implicated
      previously in skeletal disorders and detailed analysis of the biomechanical
      consequences of their deletion revealed a novel functional classification of bone
      structure and strength. The organ-specific and disease-focused strategy described
      in this study can be applied to any biological system or tractable polygenic
      disease, thus providing a general basis to define gene function in a system
      specific manner. Application of the approach to diseases affecting other
      physiological systems will help to realize the full potential of the
      International Mouse Phenotyping Consortium.

PMID- 22876198
TI  - CDK9 and H2B monoubiquitination: a well-choreographed dance.

PMID- 22876199
TI  - UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph polarize F-actin during embryonic
      morphogenesis by regulating the WAVE/SCAR actin nucleation complex.
AB  - Many cells in a developing embryo, including neurons and their axons and growth
      cones, must integrate multiple guidance cues to undergo directed growth and
      migration. The UNC-6/netrin, SLT-1/slit, and VAB-2/Ephrin guidance cues, and
      their receptors, UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph, are known to be major
      regulators of cellular growth and migration. One important area of research is
      identifying the molecules that interpret this guidance information downstream of
      the guidance receptors to reorganize the actin cytoskeleton. However, how
      guidance cues regulate the actin cytoskeleton is not well understood. We report
      here that UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph differentially regulate the
      abundance and subcellular localization of the WAVE/SCAR actin nucleation complex
      and its activator, Rac1/CED-10, in the Caenorhabditis elegans embryonic
      epidermis. Loss of any of these three pathways results in embryos that fail
      embryonic morphogenesis. Similar defects in epidermal enclosure have been
      observed when CED-10/Rac1 or the WAVE/SCAR actin nucleation complex are missing
      during embryonic development in C. elegans. Genetic and molecular experiments
      demonstrate that in fact, these three axonal guidance proteins differentially
      regulate the levels and membrane enrichment of the WAVE/SCAR complex and its
      activator, Rac1/CED-10, in the epidermis. Live imaging of filamentous actin (F
      actin) in embryos developing in the absence of individual guidance receptors
      shows that high levels of F-actin are not essential for polarized cell
      migrations, but that properly polarized distribution of F-actin is essential.
      These results suggest that proper membrane recruitment and activation of CED
      10/Rac1 and of WAVE/SCAR by signals at the plasma membrane result in polarized F
      actin that permits directed movements and suggest how multiple guidance cues can
      result in distinct changes in actin nucleation during morphogenesis.

PMID- 22876200
TI  - The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1
      adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.
AB  - The Caenorhabditis elegans left and right AWC olfactory neurons communicate to
      establish stochastic asymmetric identities, AWC(ON) and AWC(OFF), by inhibiting a
      calcium-mediated signaling pathway in the future AWC(ON) cell. NSY-4/claudin-like
      protein and NSY-5/innexin gap junction protein are the two parallel signals that
      antagonize the calcium signaling pathway to induce the AWC(ON) fate. However, it
      is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy
      5 in the AWC(ON) cell. Here we identify a microRNA, mir-71, that represses the
      TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the
      AWC(ON) identity. Similar to tir-1 loss-of-function mutants, overexpression of
      mir-71 generates two AWC(ON) neurons. tir-1 expression is downregulated through
      its 3' UTR in AWC(ON), in which mir-71 is expressed at a higher level than in
      AWC(OFF). In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC
      through the mir-71 complementary site in the tir-1 3' UTR. Our genetic studies
      suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWC(ON)
      identity in a cell autonomous manner. Furthermore, the stability of mature mir-71
      is dependent on nsy-4 and nsy-5. Together, these results provide insight into the
      mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish
      stochastic asymmetric AWC differentiation.

PMID- 22876201
TI  - Multiple roles and interactions of Tbx4 and Tbx5 in development of the
      respiratory system.
AB  - Normal development of the respiratory system is essential for survival and is
      regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are
      expressed throughout the mesenchyme of the developing lung and trachea; and,
      although multiple genes are known to be required in the epithelium, only Fgfs
      have been well studied in the mesenchyme. In this study, we investigated the
      roles of Tbx4 and Tbx5 in lung and trachea development using conditional mutant
      alleles and two different Cre recombinase transgenic lines. Loss of Tbx5 leads to
      a unilateral loss of lung bud specification and absence of tracheal specification
      in organ culture. Mutants deficient in Tbx4 and Tbx5 show severely reduced lung
      branching at mid-gestation. Concordant with this defect, the expression of
      mesenchymal markers Wnt2 and Fgf10, as well as Fgf10 target genes Bmp4 and Spry2,
      in the epithelium is downregulated. Lung branching undergoes arrest ex vivo when
      Tbx4 and Tbx5 are both completely lacking. Lung-specific Tbx4 heterozygous;Tbx5
      conditional null mice die soon after birth due to respiratory distress. These
      pups have small lungs and show severe disruptions in tracheal/bronchial cartilage
      rings. Sox9, a master regulator of cartilage formation, is expressed in the
      trachea; but mesenchymal cells fail to condense and consequently do not develop
      cartilage normally at birth. Tbx4;Tbx5 double heterozygous mutants show decreased
      lung branching and fewer tracheal cartilage rings, suggesting a genetic
      interaction. Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the
      process of lung growth and branching but not during tracheal/bronchial cartilage
      development.

PMID- 22876202
TI  - Population genomics of the facultatively mutualistic bacteria Sinorhizobium
      meliloti and S. medicae.
AB  - The symbiosis between rhizobial bacteria and legume plants has served as a model
      for investigating the genetics of nitrogen fixation and the evolution of
      facultative mutualism. We used deep sequence coverage (>100*) to characterize
      genomic diversity at the nucleotide level among 12 Sinorhizobium medicae and 32
      S. meliloti strains. Although these species are closely related and share host
      plants, based on the ratio of shared polymorphisms to fixed differences we found
      that horizontal gene transfer (HGT) between these species was confined almost
      exclusively to plasmid genes. Three multi-genic regions that show the strongest
      evidence of HGT harbor genes directly involved in establishing or maintaining the
      mutualism with host plants. In both species, nucleotide diversity is 1.5-2.5
      times greater on the plasmids than chromosomes. Interestingly, nucleotide
      diversity in S. meliloti but not S. medicae is highly structured along the
      chromosome - with mean diversity (theta(pi)) on one half of the chromosome five
      times greater than mean diversity on the other half. Based on the ratio of
      plasmid to chromosome diversity, this appears to be due to severely reduced
      diversity on the chromosome half with less diversity, which is consistent with
      extensive hitchhiking along with a selective sweep. Frequency-spectrum based
      tests identified 82 genes with a signature of adaptive evolution in one species
      or another but none of the genes were identified in both species. Based upon
      available functional information, several genes identified as targets of
      selection are likely to alter the symbiosis with the host plant, making them
      attractive targets for further functional characterization.

PMID- 22876204
TI  - Healthcare renewal.

PMID- 22876205
TI  - Biologics clinical trials, research, and FDA actions.

PMID- 22876203
TI  - Comparative analysis of the genomes of two field isolates of the rice blast
      fungus Magnaporthe oryzae.
AB  - Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases
      of rice worldwide. The fungal pathogen is notorious for its ability to overcome
      host resistance. To better understand its genetic variation in nature, we
      sequenced the genomes of two field isolates, Y34 and P131. In comparison with the
      previously sequenced laboratory strain 70-15, both field isolates had a similar
      genome size but slightly more genes. Sequences from the field isolates were used
      to improve genome assembly and gene prediction of 70-15. Although the overall
      genome structure is similar, a number of gene families that are likely involved
      in plant-fungal interactions are expanded in the field isolates. Genome-wide
      analysis on asynonymous to synonymous nucleotide substitution rates revealed that
      many infection-related genes underwent diversifying selection. The field isolates
      also have hundreds of isolate-specific genes and a number of isolate-specific
      gene duplication events. Functional characterization of randomly selected isolate
      specific genes revealed that they play diverse roles, some of which affect
      virulence. Furthermore, each genome contains thousands of loci of transposon-like
      elements, but less than 30% of them are conserved among different isolates,
      suggesting active transposition events in M. oryzae. A total of approximately 200
      genes were disrupted in these three strains by transposable elements.
      Interestingly, transposon-like elements tend to be associated with isolate
      specific or duplicated sequences. Overall, our results indicate that gain or loss
      of unique genes, DNA duplication, gene family expansion, and frequent
      translocation of transposon-like elements are important factors in genome
      variation of the rice blast fungus.

PMID- 22876206
TI  - The accelerated approval debate: faster FDA drug approvals may mean less efficacy
      data.

PMID- 22876207
TI  - Part 1: Distribution models for biologics and other specialty pharmaceutical
      products: In this first of a two-part series, we examine the distribution
      landscape for specialty pharmaceuticals. A manufacturer's strategy for the flow
      of product to patient has important implications for payers and for the success
      of a new biologic therapy.

PMID- 22876209
TI  - New care delivery models: where do biologics fit?

PMID- 22876208
TI  - Biologics and the Principles of Health Insurance: What is the purpose of health
      insurance? This review of basic insurance concepts provides a context for
      discussions about coverage of biologics.

PMID- 22876210
TI  - Next Generation Sequencing: The Next Iteration of Personalized Medicine: Next
      generation sequencing, along with expanding databases like The Cancer Genome
      Atlas, has the potential to aid rational drug discovery and streamline clinical
      trials.

PMID- 22876211
TI  - Medical Process Patents Declared Invalid: The Prometheus case restricts patent
      protection and the growth of personalized medicine.

PMID- 22876212
TI  - FDA Readies New Guidance and User Fee Program for Biosimilars: Drug
      interchangeability and user fees are contentious issues the FDA must resolve. Is
      the FDA up to the task?

PMID- 22876213
TI  - Vanderbilt pioneers bedside genetics.

PMID- 22876214
TI  - Demand for specialty drugs increasing.

PMID- 22876215
TI  - Access to Care for Methadone Maintenance Patients in the United States.
AB  - This policy commentary addresses a significant access to care issue that faces
      methadone maintenance patients seeking residential treatment in the United
      States. Methadone maintenance therapy (MMT) has demonstrated strong efficacy in
      the outpatient treatment of opiate dependence. However, many opiate dependent
      patients are also in need of more intensive interventions, such as residential
      care. Many publically-funded residential treatment programs explicitly decline to
      admit MMT patients, contending that methadone raises both clinical and
      administrative problems in treatment. Although advocates within the field believe
      that this issue is a violation of the American's with Disabilities Act (ADA) in
      the United States, no lawsuits have been brought forth, and there is no legal
      precedent or public policy to inform the debate. The present paper provides an
      overview of this problem and discusses factors that may contribute to the
      problem, including an abstinence-oriented philosophy and treatment program
      operational concerns. The paper also draws parallels between methadone and other
      medical conditions and analyzes the problem in the context of disabilities
      encompassed in the ADA. Finally, recommendations on strategies for increasing
      access to residential care for MMT patients are provided.

PMID- 22876216
TI  - Efficacy of Duloxetine in Patients with Chronic Pain Conditions.
AB  - The primary objective of this study is to review the efficacy of duloxetine in
      treating chronic pain using the Initiative on Methods, Measurement, and Pain
      Assessment in Clinical Trials (IMMPACT) recommendations for clinical significance
      across chronic pain states. These include pain intensity, patient ratings of
      overall improvement, physical functioning, and mental functioning. This review
      comprised the side-by-side analyses of 12 double-blind, placebo-controlled trials
      of duloxetine in patients with chronic pain (diabetic peripheral neuropathic
      pain, fibromyalgia, chronic pain due to osteoarthritis, and chronic low back
      pain). Patients received duloxetine (60 to 120 mg/day) or placebo. Average pain
      reduction was assessed over 3 months as the primary efficacy outcome. Other
      measures used were physical function and Patient Global Impression of
      Improvement. In 10 of the 12 studies, statistically significant greater pain
      reduction was observed for duloxetine- compared with placebo-treated patients.
      The response rates based on average pain reduction, improvement of physical
      function, and global impression were comparable across all 4 chronic pain states.
      Compared with patients on placebo, significantly more patients treated with
      duloxetine reported a moderately important pain reduction (>=30% reduction) in 9
      of the 12 studies, a minimally important improvement in physical function in 8 of
      the 12 studies, and a moderately important to substantial improvement in Patient
      Global Impression of Improvement rating in 11 of the 12 studies. The analyses
      reported here show that duloxetine is efficacious in treating chronic pain as
      demonstrated by significant improvement in pain intensity, physical functioning,
      and patient ratings of overall improvement.

PMID- 22876218
TI  - Pore formation by human stefin B in its native and oligomeric states and the
      consequent amyloid induced toxicity.
AB  - It is well documented that amyloid forming peptides and proteins interact with
      membranes and that this correlates with cytotoxicity. To introduce the theme we
      give a brief description of some amyloidogenic proteins and note their
      similarities with pore forming toxins (PFTs) and cell penetrating peptides. Human
      stefin B, a member of the family of cystatins, is an amyloidogenic protein in
      vitro. This review describes our studies of the interaction of stefin B oligomers
      and prefibrillar aggregates with model membranes leading to pore formation. We
      have studied the interaction between human stefin B and artificial membranes of
      various compositions. We also have prepared distinct sizes and morphologies of
      stefin B prefibrillar states and assessed their toxicity. Furthermore, we have
      measured electrical currents through pores formed by stefin B prefibrillar
      oligomers in a planar lipid bilayer setup. We finally discuss the possible
      functional and pathological significance of such pores formed by human stefin B.

PMID- 22876220
TI  - On the influence of emotion on conflict processing.

PMID- 22876219
TI  - Neural differentiation of transplanted neural stem cells in a rat model of
      striatal lacunar infarction: light and electron microscopic observations.
AB  - The increased risk and prevalence of lacunar stroke and Parkinson's disease (PD)
      makes the search for better experimental models an important requirement for
      translational research. In this study we assess ischemic damage of the
      nigrostriatal pathway in a model of lacunar stroke evoked by damaging the
      perforating arteries in the territory of the substantia nigra (SN) of the rat
      after stereotaxic administration of endothelin-1 (ET-1), a potent vasoconstrictor
      peptide. We hypothesized that transplantation of neural stem cells (NSCs) with
      the capacity of differentiating into diverse cell types such as neurons and glia,
      but with limited proliferation potential, would constitute an alternative and/or
      adjuvant therapy for lacunar stroke. These cells showed neuritogenic activity in
      vitro and a high potential for neural differentiation. Light and electron
      microscopy immunocytochemistry was used to characterize GFP-positive neurons
      derived from the transplants. 48 h after ET-1 injection, we characterized an area
      of selective degeneration of dopaminergic neurons within the nigrostriatal
      pathway characterized with tissue necrosis and glial scar formation, with
      subsequent behavioral signs of Parkinsonism. Light microscopy showed that grafted
      cells within the striatal infarction zone differentiated with a high yield into
      mature glial cells (GFAP-positive) and neuron types present in the normal
      striatum. Electron microscopy revealed that NSCs-derived neurons integrated into
      the host circuitry establishing synaptic contacts, mostly of the asymmetric type.
      Astrocytes were closely associated with normal small-sized blood vessels in the
      area of infarct, suggesting a possible role in the regulation of the blood brain
      barrier and angiogenesis. Our results encourage the use of NSCs as a cell
      replacement therapy for the treatment of human vascular Parkinsonism.

PMID- 22876217
TI  - Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying
      alcohol and nicotine addictions.
AB  - Addictive drugs can activate systems involved in normal reward-related learning,
      creating long-lasting memories of the drug's reinforcing effects and the
      environmental cues surrounding the experience. These memories significantly
      contribute to the maintenance of compulsive drug use as well as cue-induced
      relapse which can occur even after long periods of abstinence. Synaptic
      plasticity is thought to be a prominent molecular mechanism underlying drug
      induced learning and memories. Ethanol and nicotine are both widely abused drugs
      that share a common molecular target in the brain, the neuronal nicotinic
      acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that
      are vastly distributed throughout the brain and play a key role in synaptic
      neurotransmission. In this review, we will delineate the role of nAChRs in the
      development of ethanol and nicotine addiction. We will characterize both ethanol
      and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in
      several key brain areas that are important for addiction. Finally, we will
      discuss some of the behavioral outcomes of drug-induced synaptic plasticity in
      animal models. An understanding of the molecular and cellular changes that occur
      following administration of ethanol and nicotine will lead to better therapeutic
      strategies.

PMID- 22876221
TI  - The trade-offs of emotional reactivity for youths' social information processing
      in the context of maternal depression.
AB  - Although research demonstrates that emotional experiences can influence cognitive
      processing, little is known about individual differences in this association,
      particularly in youth. The present study examined how the emotional backdrop of
      the caregiving environment, as reflected in exposure to maternal depression and
      anxiety, was linked to biases in youths' cognitive processing of mother-referent
      information. Further, we investigated whether this association differed according
      to variation in youths' emotional reactivity to stress. Youth (50 boys, 46 girls;
      M age = 12.36, SD = 1.05) completed a behavioral task assessing cognitive bias.
      Semi-structured interviews were administered to assess (a) youths' emotional
      reactivity to naturally occurring stressors, and (b) maternal depression and
      anxiety. Hierarchical multiple regression analyses revealed that emotional
      reactivity to interpersonal stressors moderated the linkage between maternal
      depression and cognitive bias such that maternal depression predicted a greater
      negative bias in youth exhibiting high and average, but not low, levels of
      emotional reactivity. At low levels of maternal depression, youth with heightened
      interpersonal emotional reactivity showed a greater positive cognitive bias. This
      pattern of effects was specific to interpersonal (but not non-interpersonal)
      emotional reactivity and to maternal depression (but not anxiety). These findings
      illuminate one personal characteristic of youth that moderates emotion-cognition
      linkages, and reveal that emotional reactivity both enhances and impairs youths'
      cognitive processing as a function of socialization context.

PMID- 22876223
TI  - Attention and awareness each influence amygdala activity for dynamic bodily
      expressions-a short review.
AB  - The amygdala (AMG) has long been viewed as the gateway to sensory processing of
      emotions and is also known to play an important role at the interface between
      cognition and emotion. However, the debate continues on whether AMG activation is
      independent of attentional demands. Recently, researchers started exploring AMG
      functions using dynamic stimuli rather than the traditional pictures of facial
      expressions. Our present goal is to review some recent studies using dynamic
      stimuli to investigate AMG activation and discuss the impact of different viewing
      conditions, including oddball detection, explicit or implicit recognition,
      variable cognitive task load, and non-conscious perception. In the second part,
      we sketch a dynamic dual route perspective of affective perception and discuss
      the implications for AMG activity. We sketch a dynamic dual route perspective of
      affective perception. We argue that this allows for multiple AMG involvement in
      separate networks and at different times in the processing streams. Attention has
      a different impact on these separate but interacting networks. Route I is engaged
      in early emotion processing, is partly supported by AMG activity, and is possibly
      independent of attention, whereas activity related to late emotion processing is
      influenced by attention. Route II is a cortical-based network that underlies body
      recognition and action representation. The end result of route I and II is
      reflexive and voluntary behavior, respectively. We conclude that using dynamic
      emotion stimuli and a dynamic dual route model of affective perception can
      provide new insights into the varieties of AMG activation.

PMID- 22876222
TI  - Hypotheses relating to the function of the claustrum.
AB  - This paper present a new hypothesis as to the function of the claustrum. Our
      basic premise is that the claustrum functions as a detector and integrator of
      synchrony in the axonal trains in its afferent inputs. In the first place an
      unexpected stimulus sets up a processed signal to the sensory cortex that
      initiates a focus of synchronized gamma oscillations therein. This focus may then
      interact with a general alerting signal conveyed from the reticular formation via
      cholinergic mechanisms, and with other salient activations set up by the stimulus
      in other sensory pathways that are relayed to the cortex. This activity is
      relayed from the cortex to the claustrum, which then processes these several
      inputs by means of multiple competitive intraclaustral synchronized oscillations
      at different frequencies. Finally it modulates the synchronized outputs that the
      claustrum distributes to most cortical and many subcortical structures, including
      the motor cortex. In this way, during multicenter perceptual and cognitive
      operations, reverberating claustro-cortical loops potentiate weak intracortical
      synchronizations by means of connected strong intraclaustral synchronizations.
      These may also occur without a salient stimulus. By this mechanism, the claustrum
      may play a strong role in the control of interactive processes in different parts
      of the brain, and in the control of voluntary behavior. These may include the
      neural correlates of consciousness. We also consider the role of GABAergic
      mechanisms and deafferentation plasticity.

PMID- 22876224
TI  - Octopaminergic modulation of contrast sensitivity.
AB  - Sensory systems adapt to prolonged stimulation by decreasing their response to
      continuous stimuli. Whereas visual motion adaptation has traditionally been
      studied in immobilized animals, recent work indicates that the animal's
      behavioral state influences the response properties of higher-order motion vision
      sensitive neurons. During insect flight octopamine is released, and
      pharmacological octopaminergic activation can induce a fictive locomotor state.
      In the insect optic ganglia, lobula plate tangential cells (LPTCs) spatially pool
      input from local elementary motion detectors (EMDs) that correlate luminosity
      changes from two spatially discrete inputs after delaying the signal from one.
      The LPTC velocity optimum thereby depends on the spatial separation of the inputs
      and on the EMD's delay properties. Recently it was shown that behavioral activity
      increases the LPTC velocity optimum, with modeling suggesting this to originate
      in the EMD's temporal delay filters. However, behavior induces an additional post
      EMD effect: the LPTC membrane conductance increases in flying flies. To
      physiologically investigate the degree to which activity causes presynaptic and
      postsynaptic effects, we conducted intracellular recordings of Eristalis
      horizontal system (HS) neurons. We constructed contrast response functions before
      and after adaptation at different temporal frequencies, with and without the
      octopamine receptor agonist chlordimeform (CDM). We extracted three motion
      adaptation components, where two are likely to be generated presynaptically of
      the LPTCs, and one within them. We found that CDM affected the early, EMD
      associated contrast gain reduction, temporal frequency dependently. However, a
      CDM-induced change of the HS membrane conductance disappeared during and after
      visual stimulation. This suggests that physical activity mainly affects motion
      adaptation presynaptically of LPTCs, whereas post-EMD effects have a minimal
      effect.

PMID- 22876226
TI  - Neural computations underlying social risk sensitivity.
AB  - Under standard models of expected utility, preferences over stochastic events are
      assumed to be independent of the source of uncertainty. Thus, in decision-making,
      an agent should exhibit consistent preferences, regardless of whether the
      uncertainty derives from the unpredictability of a random process or the
      unpredictability of a social partner. However, when a social partner is the
      source of uncertainty, social preferences can influence decisions over and above
      pure risk attitudes (RA). Here, we compared risk-related hemodynamic activity and
      individual preferences for two sets of options that differ only in the social or
      non-social nature of the risk. Risk preferences in social and non-social contexts
      were systematically related to neural activity during decision and outcome phases
      of each choice. Individuals who were more risk averse in the social context
      exhibited decreased risk-related activity in the amygdala during non-social
      decisions, while individuals who were more risk averse in the non-social context
      exhibited the opposite pattern. Differential risk preferences were similarly
      associated with hemodynamic activity in ventral striatum at the outcome of these
      decisions. These findings suggest that social preferences, including aversion to
      betrayal or exploitation by social partners, may be associated with variability
      in the response of these subcortical regions to social risk.

PMID- 22876228
TI  - Predicting "When" Using the Motor System's Beta-Band Oscillations.

PMID- 22876227
TI  - Beyond the blank slate: routes to learning new coordination patterns depend on
      the intrinsic dynamics of the learner-experimental evidence and theoretical
      model.
AB  - Using an approach that combines experimental studies of bimanual movements to
      visual stimuli and theoretical modeling, the present paper develops a dynamical
      account of sensorimotor learning, that is, how new skills are acquired and old
      ones modified. A significant aspect of our approach is the focus on the
      individual learner as the basic unit of analysis, in particular the
      quantification of predispositions and capabilities that the individual learner
      brings to the learning environment. Such predispositions constitute the learner's
      behavioral repertoire, captured here theoretically as a dynamical landscape
      ("intrinsic dynamics"). The learning process is demonstrated to not only lead to
      a relatively permanent improvement of performance in the required task-the usual
      outcome-but also to alter the individual's entire repertoire. Changes in the
      dynamical landscape due to learning are shown to result from two basic mechanisms
      or "routes": bifurcation and shift. Which mechanism is selected depends the
      initial individual repertoire before new learning begins. Both bifurcation and
      shift mechanisms are accommodated by a dynamical model, a relatively
      straightforward development of the well-established HKB model of movement
      coordination. Model simulations show that although environmental or task demands
      may be met equally well using either mechanism, the bifurcation route results in
      greater stabilization of the to-be-learned behavior. Thus, stability not (or not
      only) error is demonstrated to be the basis of selection, both of a new pattern
      of behavior and the path (smooth shift versus abrupt qualitative change) that
      learning takes. In line with these results, recent neurophysiological evidence
      indicates that stability is a relevant feature around which brain activity is
      organized while an individual performs a coordination task. Finally, we explore
      the consequences of the dynamical approach to learning for theories of biological
      change.

PMID- 22876229
TI  - Task-dependent neural bases of perceiving emotionally expressive targets.
AB  - SOCIAL COGNITION IS FUNDAMENTALLY INTERPERSONAL: individuals' behavior and
      dispositions critically affect their interaction partners' information
      processing. However, cognitive neuroscience studies, partially because of
      methodological constraints, have remained largely "perceiver-centric": focusing
      on the abilities, motivations, and goals of social perceivers while largely
      ignoring interpersonal effects. Here, we address this knowledge gap by examining
      the neural bases of perceiving emotionally expressive and inexpressive social
      "targets." Sixteen perceivers were scanned using fMRI while they watched targets
      discussing emotional autobiographical events. Perceivers continuously rated each
      target's emotional state or eye-gaze direction. The effects of targets' emotional
      expressivity on perceiver's brain activity depended on task set: when perceivers
      explicitly attended to targets' emotions, expressivity predicted activity in
      neural structures-including medial prefrontal and posterior cingulate cortex
      associated with drawing inferences about mental states. When perceivers instead
      attended to targets' eye-gaze, target expressivity predicted activity in regions
      including somatosensory cortex, fusiform gyrus, and motor cortex-associated with
      monitoring sensorimotor states and biological motion. These findings suggest that
      expressive targets affect information processing in manner that depends on
      perceivers' goals. More broadly, these data provide an early step toward
      understanding the neural bases of interpersonal social cognition.

PMID- 22876230
TI  - The elusive nature of white matter damage in anatomo-clinical correlations.

PMID- 22876225
TI  - Context, emotion, and the strategic pursuit of goals: interactions among multiple
      brain systems controlling motivated behavior.
AB  - Motivated behavior exhibits properties that change with experience and partially
      dissociate among a number of brain structures. Here, we review evidence from
      rodent experiments demonstrating that multiple brain systems acquire information
      in parallel and either cooperate or compete for behavioral control. We propose a
      conceptual model of systems interaction wherein a ventral emotional memory
      network involving ventral striatum (VS), amygdala, ventral hippocampus, and
      ventromedial prefrontal cortex triages behavioral responding to stimuli according
      to their associated affective outcomes. This system engages autonomic and
      postural responding (avoiding, ignoring, approaching) in accordance with
      associated stimulus valence (negative, neutral, positive), but does not engage
      particular operant responses. Rather, this emotional system suppresses or
      invigorates actions that are selected through competition between goal-directed
      control involving dorsomedial striatum (DMS) and habitual control involving
      dorsolateral striatum (DLS). The hippocampus provides contextual specificity to
      the emotional system, and provides an information rich input to the goal-directed
      system for navigation and discriminations involving ambiguous contexts, complex
      sensory configurations, or temporal ordering. The rapid acquisition and high
      capacity for episodic associations in the emotional system may unburden the more
      complex goal-directed system and reduce interference in the habit system from
      processing contingencies of neutral stimuli. Interactions among these systems
      likely involve inhibitory mechanisms and neuromodulation in the striatum to form
      a dominant response strategy. Innate traits, training methods, and task demands
      contribute to the nature of these interactions, which can include incidental
      learning in non-dominant systems. Addition of these features to reinforcement
      learning models of decision-making may better align theoretical predictions with
      behavioral and neural correlates in animals.

PMID- 22876231
TI  - Nicotine exposure during adolescence alters the rules for prefrontal cortical
      synaptic plasticity during adulthood.
AB  - The majority of adolescents report to have smoked a cigarette at least once.
      Adolescence is a critical period of brain development during which maturation of
      areas involved in cognitive functioning, such as the medial prefrontal cortex
      (mPFC), is still ongoing. Tobacco smoking during this age may compromise the
      normal course of prefrontal development and lead to cognitive impairments in
      later life. In addition, adolescent smokers suffer from attention deficits, which
      progress with the years of smoking. Recent studies in rodents reveal the
      molecular changes induced by adolescent nicotine exposure that alter the
      functioning of synapses in the PFC and underlie the lasting effects on cognitive
      function. In particular, the expression and function of metabotropic glutamate
      receptors (mGluRs) are changed and this has an impact on short- and long-term
      plasticity of glutamatergic synapses in the PFC and ultimately on the attention
      performance. Here, we review and discuss these recent findings.

PMID- 22876233
TI  - The Role of Astrocytes in Metabolism and Neurotoxicity of the Pyrrolizidine
      Alkaloid Monocrotaline, the Main Toxin of Crotalaria retusa.
AB  - The metabolic interactions and signaling between neurons and glial cells are
      necessary for the development and maintenance of brain functions and structures
      and for neuroprotection, which includes protection from chemical attack.
      Astrocytes are essential for cerebral detoxification and present an efficient and
      specific cytochrome P450 enzymatic system. Whilst Crotalaria (Fabaceae,
      Leguminosae) plants are used in popular medicine, they are considered toxic and
      can cause damage to livestock and human health problems. Studies in animals have
      shown cases of poisoning by plants from the genus Crotalaria, which induced
      damage to the central nervous system. This finding has been attributed to the
      toxic effects of the pyrrolizidine alkaloid (PA) monocrotaline (MCT). The
      involvement of P450 enzymatic systems in MCT hepatic and pulmonary metabolism and
      toxicity has been elucidated, but little is known about the pathways implicated
      in the bioactivation of these systems and the direct contribution of these
      systems to brain toxicity. This review will present the main toxicological
      aspects of the Crotalaria genus that are established in the literature and recent
      findings describing the mechanisms involved in the neurotoxic effects of MCT,
      which was extracted from Crotalaria retusa, and its interaction with neurons in
      isolated astrocytes.

PMID- 22876232
TI  - The KCNE Tango - How KCNE1 Interacts with Kv7.1.
AB  - The classical tango is a dance characterized by a 2/4 or 4/4 rhythm in which the
      partners dance in a coordinated way, allowing dynamic contact. There is a
      surprising similarity between the tango and how KCNE beta-subunits "dance" to the
      fast rhythm of the cell with their partners from the Kv channel family. The five
      KCNE beta-subunits interact with several members of the Kv channels, thereby
      modifying channel gating via the interaction of their single transmembrane
      spanning segment, the extracellular amino terminus, and/or the intracellular
      carboxy terminus with the Kv alpha-subunit. Best studied is the molecular basis
      of interactions between KCNE1 and Kv7.1, which, together, supposedly form the
      native cardiac I(Ks) channel. Here we review the current knowledge about
      functional and molecular interactions of KCNE1 with Kv7.1 and try to summarize
      and interpret the tango of the KCNEs.

PMID- 22876234
TI  - Aldo-Keto Reductases 1B in Endocrinology and Metabolism.
AB  - The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many
      research because of its role in diabetic complications. The starting point of
      these alterations is the massive entry of glucose in polyol pathway where it is
      converted into sorbitol by this enzyme. However, the issue of AR function in non
      diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and
      Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making
      functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b
      members share at least 65% protein identity and the general ability to reduce
      many redundant substrates such as aldehydes provided from lipid peroxidation,
      steroids and their by-products, and xenobiotics in vitro. Based on these
      properties, AKR1B/Akr1b are generally considered as detoxifying enzymes.
      Considering that divergences should be more informative than similarities to help
      understanding their physiological functions, we chose to review specific
      hallmarks of each human/mouse isoforms by focusing on tissue distribution and
      specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous
      expression, AR-like proteins exhibit tissue-specific patterns of expression. We
      focused on three organs where certain isoforms are enriched, the adrenal gland,
      enterohepatic, and adipose tissues and tried to connect recent enzymatic and
      regulation data with endocrine and metabolic functions of these organs. We
      presented recent mouse models showing unsuspected physiological functions in the
      regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond
      the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these
      recent reports provide growing evidences that they are able to modify or generate
      signal molecules. This conceptually shifts this class of enzymes from unenviable
      status of scavenger to upper class of messengers.

PMID- 22876235
TI  - Dynamic coding of signed quantities in cortical feedback circuits.
AB  - In the early sensory and motor areas of the cortex, individual neurons transmit
      information about specific sensory features via a peaked response. This concept
      has been crystallized as "labeled lines," to denote that axons communicate the
      specific properties of their sensory or motor parent cell. Such cells also can be
      characterized as being polarized, that is, as representing a signed quantity that
      is either positive or negative. We show in a model simulation that there are two
      important consequences when learning receptive fields using such signed codings
      in circuits that subtract different inputs. The first is that, in feedback
      circuits using labeled lines, such arithmetic operations need to be distributed
      across multiple distinct pathways. The second consequence is that such pathways
      must be necessarily dynamic, i.e., that synapses can grow and retract when
      forming receptive fields. The model monitors the breaking and growing of new
      circuit connections when their synapses need to change polarities and predicts
      that the rate of such changes should be inversely correlated with the progress of
      receptive field formation.

PMID- 22876236
TI  - Diagnosing medication non-adherence in a patient with myocardial infarction.
AB  - BACKGROUND: Medication non-adherence continues to be a major challenge facing the
      healthcare system. A case is presented of a 48-year-old man with myocardial
      infarction who was found to be non-adherent to multiple medications. Conceptual
      models are reviewed along with current approaches for assessment and treatment of
      medication non-adherence. DESIGN: Case report and literature review. DISCUSSION:
      A theoretical model for medication non-adherence built on the Theory of Planned
      Behavior is presented. Empirical evidence is reviewed for determinants of non
      adherent behavior such as health beliefs and self-efficacy. Current methods to
      assess medication non-adherence, including self-report, pill count, biological
      drug levels, pharmacy refill, and electronic bottles are summarized along with
      their limitations. Finally, an individualized approach for assessment is
      described using the case presented and the conceptual framework outlined above.
      Follow-up for the patient and potential interventions to improve medication
      adherence are discussed. CONCLUSION: Despite the challenges, a conceptual
      framework for medication non-adherence can guide assessment and treatment.
      Further research for innovative and effective methods to detect and treat
      medication non-adherence is urgently needed to aid clinicians in treating this
      pervasive behavioral problem.

PMID- 22876237
TI  - Using text messages to bridge the intention-behavior gap? A pilot study on the
      use of text message reminders to increase objectively assessed physical activity
      in daily life.
AB  - Sedentarism is a serious health concern in industrialized countries throughout
      the world. We examined whether a text message-based intervention, targeted at
      increasing daily levels of physical activity, would be more effective than a
      standard psychoeducational intervention and a control condition. Sixty-three
      individuals (43 women) with a mean age of 23.7 years participated in the study.
      They were randomly assigned to a psychoeducational standard intervention; an
      augmented intervention with additional short text messages sent to the mobile
      phones to remind participants of their action plans, and a control condition.
      Objectively assessed physical activity and self-efficacy were assessed pre- and
      post-intervention. Participants in the control condition showed a significant
      decline in physical activity from pre-assessment to post-assessment, whereas
      participants in both intervention arms exhibited a slight increase. Moreover, the
      augmented intervention resulted in a marginally significant increase in self
      efficacy, whereas the standard intervention resulted in a significant decrease.
      The findings suggest that short text messages reminding individuals of their
      action plans are not more effective than an intervention without text messages,
      although there seems to be a beneficial effect on self-efficacy, which might
      facilitate behavior change in the long-term. Challenging aspects of the research
      design (e.g., reactivity of the assessment protocol) are discussed and
      suggestions for future research are highlighted.

PMID- 22876238
TI  - The role of head and neck squamous cell carcinoma cancer stem cells in
      tumorigenesis, metastasis, and treatment failure.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide. Despite advances in diagnostic and therapeutic methods, survival of
      HNSCC remains unchanged over the last 30 years with treatment failure and
      metastases being the strongest indicators of poor outcome. Cancer stem cells
      (CSC) have been identified in multiple other solid tumors, including breast,
      prostate, and pancreatic carcinoma. Recently, a subpopulation of tumor cells has
      been identified in HNSCC based on the overexpression of the cellular marker CD44
      and increased activity of aldehyde dehydrogenase. These cells have been
      designated CSC based on their stem cell-like properties: self-renewal,
      tumorigenesis, and the ability to recapitulate a heterogeneous tumor. Recent work
      looking at the role of HNSCC CSC in tumorigenesis has shown that CSC have a
      greater capacity for tumor growth, increased motility, and invasive
      characteristics; in vivo experiments confirm greater metastatic potential in CSC
      compared to non-CSC. Clinically, CSC enrichment has been shown to be enhanced in
      recurrent disease, treatment failure, and metastasis. CSC represent a novel
      target of study given their slow growth and innate mechanisms conferring
      treatment resistance. Further understanding of their unique phenotype may reveal
      potential molecular targets to improve therapeutic and survival outcomes in
      patients with HNSCC.

PMID- 22876239
TI  - When should we expect microbial phenotypic traits to predict microbial
      abundances?
AB  - Species' phenotypic traits may predict their relative abundances. Intuitively,
      this is because locally abundant species have traits making them well-adapted to
      local abiotic and biotic conditions, while locally rare species are not as well
      adapted. But this intuition may not be valid. If competing species vary in how
      well-adapted they are to local conditions, why doesn't the best-adapted species
      simply exclude the others entirely? But conversely, if species exhibit niche
      differences that allow them to coexist, then by definition there is no single
      best adapted species. Rather, demographic rates depend on species' relative
      abundances, so that phenotypic traits conferring high adaptedness do not
      necessarily confer high abundance. I illustrate these points using a simple
      theoretical model incorporating adjustable levels of "adaptedness" and "niche
      differences." Even very small niche differences can weaken or even reverse the
      expected correlation between adaptive traits and abundance. Conversely, adaptive
      traits confer high abundance when niche differences are very strong. Future work
      should be directed toward understanding the link between phenotypic traits and
      frequency-dependence of demographic rates.

PMID- 22876240
TI  - Origin, diversity, and maturation of human antiviral antibodies analyzed by high
      throughput sequencing.
AB  - Our understanding of how antibodies are generated and function could help develop
      effective vaccines and antibody-based therapeutics against viruses such as HIV-1,
      SARS coronavirus (SARS CoV), and Hendra and Nipah viruses (henipaviruses).
      Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed
      in patients, elicitation of such bnAbs remains a major challenge when compared to
      other viral targets. We previously hypothesized that HIV-1 could have evolved a
      strategy to evade the immune system due to absent or very weak binding of
      germline antibodies to the conserved epitopes that may not be sufficient to
      initiate and/or maintain an effective immune response. To further explore our
      hypothesis, we used the 454 sequence analysis of a large naive library of human
      IgM antibodies which had been used for selecting antibodies against SARS CoV
      receptor-binding domain (RBD), and soluble G proteins (sG) of henipaviruses. We
      found that the human IgM repertoires from the 454 sequencing have diverse
      germline usages, recombination patterns, junction diversity, and a lower extent
      of somatic mutation. In this study, we identified antibody maturation
      intermediates that are related to bnAbs against the HIV-1 and other viruses as
      observed in normal individuals, and compared their genetic diversity and somatic
      mutation level along with available structural and functional data. Further
      computational analysis will provide framework for understanding the underlying
      genetic and molecular determinants related to maturation pathways of antiviral
      bnAbs that could be useful for applying novel approaches to the design of
      effective vaccine immunogens and antibody-based therapeutics.

PMID- 22876241
TI  - Viral tropism.

PMID- 22876242
TI  - Intervention of PKC-theta as an immunosuppressive regimen.
AB  - PKC-theta is selectively enriched in T cells and specifically translocates to
      immunological synapse where it mediates critical T cell receptor signals required
      for T cell activation, differentiation, and survival. T cells deficient in PKC
      theta are defective in their ability to differentiate into inflammatory effector
      cells that mediate actual immune responses whereas, their differentiation into
      regulatory T cells (Treg) that inhibits the inflammatory T cells is enhanced.
      Therefore, the manipulation of PKC-theta activity can shift the ratio between
      inflammatory effector T cells and inhibitory Tregs, to control T cell-mediated
      immune responses that are responsible for autoimmunity and allograft rejection.
      Indeed, PKC-theta-deficient mice are resistant to the development of several Th2
      and Th17-dependent autoimmune diseases and are defective in mounting alloimmune
      responses required for rejection of transplanted allografts and graft-versus-host
      disease. Selective inhibition of PKC-theta is therefore considered as a potential
      treatment for prevention of autoimmune diseases and allograft rejection.

PMID- 22876244
TI  - Effect of Arthritic Synovial Fluids on the Expression of Immunomodulatory Factors
      by Mesenchymal Stem Cells: An Explorative in vitro Study.
AB  - BACKGROUND: In diseased joints, the catabolic environment results in progressive
      joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by
      secreting anti-inflammatory factors. To exert these effects, MSCs need to be
      triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a
      treatment for diseased joints, we studied the effect of synovial fluid (SF) from
      donors with different joint diseases and donors without joint pathology on the
      immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of
      diseased joints influences the immunomodulatory effects of MSCs. MATERIALS AND
      METHODS: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six
      rheumatoid arthritis (RA) donors and three donors without joint pathology were
      used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3
      dioxygenase (IDO) were analyzed. l-kynurenine concentration in conditioned medium
      (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs.
      Furthermore, the effect of CM with SF on proliferation of activated lymphocytes
      was analyzed. RESULTS: Addition of SF significantly up-regulated the mRNA
      expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher
      expression of IDO than SF(control), although no difference in IDO activity of the
      MSCs could be shown with a l-kynurenine assay. Medium conditioned by MSCs with
      SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than
      medium conditioned by MSCs without SF or with SF(control). DISCUSSION: SF can
      influence the expression of genes involved in immunomodulation by MSCs and the
      effect on lymphocyte proliferation. We found indications for disease-specific
      differences between SFs but the variation between donors, even within one disease
      group was high. These data warrant further research to examine the potential
      application of MSC therapy in arthritic joints.

PMID- 22876243
TI  - Pharmacological targeting of phosphoinositide lipid kinases and phosphatases in
      the immune system: success, disappointment, and new opportunities.
AB  - The predominant expression of the gamma and delta isoforms of PI3K in cells of
      hematopoietic lineage prompted speculation that inhibitors of these isoforms
      could offer opportunities for selective targeting of PI3K in the immune system in
      a range of immune-related pathologies. While there has been some success in
      developing PI3Kdelta inhibitors, progress in developing selective inhibitors of
      PI3Kgamma has been rather disappointing. This has prompted the search for
      alternative targets with which to modulate PI3K signaling specifically in the
      immune system. One such target is the SH2 domain-containing inositol-5
      phosphatase-1 (SHIP-1) which de-phosphorylates PI(3,4,5)P(3) at the D5 position
      of the inositol ring to create PI(3,4)P(2). In this article, we first describe
      the current state of PI3K isoform-selective inhibitor development. We then focus
      on the structure of SHIP-1 and its function in the immune system. Finally, we
      consider the current state of development of small molecule compounds that
      potently and selectively modulate SHIP activity and which offer novel
      opportunities to manipulate PI3K mediated signaling in the immune system.

PMID- 22876245
TI  - APECED: is this a model for failure of T cell and B cell tolerance?
AB  - In APECED, the key abnormality is in the T cell defect that may lead to tissue
      destruction chiefly in endocrine organs. Besides, APECED is characterized by high
      titer antibodies against a wide variety of cytokines that could partly be
      responsible for the clinical symptoms during APECED, mainly chronic mucocutaneous
      candidiasis, and linked to antibodies against Th17 cells effector molecules, IL
      17 and IL-22. On the other hand, the same antibodies, together with antibodies
      against type I interferons may prevent the patients from other immunological
      diseases, such as psoriasis and systemic lupus erythematous. The same effector
      Th17 cells, present in the lymphocytic infiltrate of target organs of APECED,
      could be responsible for the tissue destruction. Here again, the antibodies
      against the corresponding effector molecules, anti-IL-17 and anti-IL-22 could be
      protective. The occurrence of several effector mechanisms (CD4(+) Th17 cell and
      CD8(+) CTL and the effector cytokines IL-17 and IL-22), and simultaneous
      existence of regulatory mechanisms (CD4(+) Treg and antibodies neutralizing the
      effect of the effector cytokines) may explain the polymorphism of APECED. Almost
      all the patients develop the characteristic manifestations of the complex, but
      temporal course and severity of the symptoms vary considerably, even among
      siblings. The autoantibody profile does not correlate with the clinical picture.
      One could speculate that a secondary homeostatic balance between the harmful
      effector mechanisms, and the favorable regulatory mechanisms, finally define both
      the extent and severity of the clinical condition in the AIRE defective
      individuals. The proposed hypothesis that in APECED, in addition to strong tissue
      destructive mechanisms, a controlling regulatory mechanism does exist, allow us
      to conclude that APECED could be treated, and even cured, with immunological
      manipulation.

PMID- 22876246
TI  - Dendritic cells a double-edge sword in autoimmune responses.
AB  - Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in
      regulating innate and adaptive immune responses. In autoimmunity, DC act as a
      double-edged sword since on one hand they initiate adaptive self-reactive
      responses and on the other they play a pivotal role in promoting and maintaining
      tolerance. Thus, DC are the most important cells in either triggering self
      specific responses or in negatively regulating auto-reactive responses. The
      latter function is mediated by DC in the steady-state or specialized subsets of
      DC, named tolerogenic DC. Clinical and experimental evidence indicate that
      prolonged presentation of self-antigens by DC is crucial for the development of
      destructive autoimmune diseases, and defects in tolerogenic DC functions
      contribute to eradication of self-tolerance. In recent years, DC have emerged as
      therapeutic targets for limiting their immunogenicity against self-antigens,
      while tolerogenic DC have been conceived as therapeutic tools to restore
      tolerance. The purpose of this review is to give a general overview of the
      current knowledge on the pathogenic role of DC in patients affected by autoimmune
      diseases. In addition, the protective role of tolerogenic DC will be addressed.
      The currently applied strategies to block immune activation or to exploit the
      tolerogenic potential of DC will be discussed.

PMID- 22876247
TI  - The Mechanism of Action of Antimicrobial Peptides: Lipid Vesicles vs. Bacteria.

PMID- 22876249
TI  - Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling and firm
      adhesion.
AB  - Very Late Antigen-4 (CD49d/CD29, alpha4 beta1) and Lymphocyte Function-associated
      Antigen-1 (CD11a/CD18, alphaL beta2) integrins are representatives of a large
      family of adhesion receptors widely expressed on immune cells. They participate
      in cell recruitment to sites of inflammation, as well as multiple immune cell
      interactions. A unique feature of integrins is that integrin-dependent cell
      adhesion can be rapidly and reversibly modulated in response to cell signaling,
      because of a series of conformational changes within the molecule, which include
      changes in the affinity of the ligand binding pocket, molecular extension
      (unbending) and others. Here, we provide a concise comparative analysis of the
      conformational regulation of the two integrins with specific attention to the
      physiological differences between these molecules. We focus on recent data
      obtained using a novel technology, based on small fluorescent ligand-mimicking
      probes for the detection of integrin conformation in real-time on live cells at
      natural receptor abundance.

PMID- 22876248
TI  - Novel identified receptors on mast cells.
AB  - Mast cells (MC) are major participants in the allergic reaction. In addition they
      possess immunomodulatory roles in the innate and adaptive immune reactions. Their
      functions are modulated through a number of activating and inhibitory receptors
      expressed on their surface. This review deals with some of the most recently
      described receptors, their expression patterns, ligand(s), signal transduction
      mechanisms, possible cross-talk with other receptors and, last but not least,
      regulatory functions that the MC can perform based on their receptor expression
      in health or in disease. Where the receptor role on MC is still not clear,
      evidences from other hematopoietic cells expressing them is provided as a
      possible insight for their function on MC. Suggested strategies to modulate these
      receptors' activity for the purpose of therapeutic intervention are also
      discussed.

PMID- 22876250
TI  - Phosphonate analogs of 2-oxoglutarate perturb metabolism and gene expression in
      illuminated Arabidopsis leaves.
AB  - Although the role of the 2-oxoglutarate dehydrogenase complex (2-OGDHC) has
      previously been demonstrated in plant heterotrophic tissues its role in
      photosynthetically active tissues remains poorly understood. By using a
      combination of metabolite and transcript profiles we here investigated the
      function of 2-OGDHC in leaves of Arabidopsis thaliana via use of specific
      phosphonate inhibitors of the enzyme. Incubation of leaf disks with the
      inhibitors revealed that they produced the anticipated effects on the in situ
      enzyme activity. In vitro experiments revealed that succinyl phosphonate (SP) and
      a carboxy ethyl ester of SP are slow-binding inhibitors of the 2-OGDHC. Our
      results indicate that the reduced respiration rates are associated with changes
      in the regulation of metabolic and signaling pathways leading to an imbalance in
      carbon-nitrogen metabolism and cell homeostasis. The inducible alteration of
      primary metabolism was associated with altered expression of genes belonging to
      networks of amino acids, plant respiration, and sugar metabolism. In addition, by
      using isothermal titration calorimetry we excluded the possibility that the
      changes in gene expression resulted from an effect on 2-oxoglutarate (2OG)
      binding to the carbon/ATP sensing protein PII. We also demonstrated that the 2OG
      degradation by the 2-oxoglutarate dehydrogenase strongly influences the
      distribution of intermediates of the tricarboxylic acid (TCA) cycle and the GABA
      shunt. Our results indicate that the TCA cycle activity is clearly working in a
      non-cyclic manner upon 2-OGDHC inhibition during the light period.

PMID- 22876251
TI  - ER Import Sites and Their Relationship to ER Exit Sites: A New Model for
      Bidirectional ER-Golgi Transport in Higher Plants.
AB  - Per definition, ER exit sites are COPII vesiculation events at the surface of the
      ER and in higher plants are only visualizable in the electron microscope through
      cryofixation techniques. Fluorescent COPII labeling moves with Golgi stacks and
      locates to the interface between the ER and the Golgi. In contrast, the domain of
      the ER where retrograde COPI vesicles fuse, i.e., ER import sites (ERIS), has
      remained unclear. To identify ERIS we have employed ER-located SNAREs and
      tethering factors. We screened several SNAREs (SYP81, the SYP7 family, and USE1)
      to find a SNARE whose overexpression did not disrupt ER-Golgi traffic and which
      gave rise to discrete fluorescent punctae when expressed with an XFP tag. Only
      the Qc-SNARE SYP72 fulfilled these criteria. When coexpressed with SYP72-YFP,
      both the type I-membrane protein RFP-p24delta5 and the luminal marker CFP-HDEL
      whose ER localization are due to an efficient COPI-mediated recycling, form
      nodules along the tubular ER network. SYP72-YFP colocalizes with these nodules
      which are not seen when RFP-p24delta5 or CFP-HDEL is expressed alone or when
      SYP72-YFP is coexpressed with a mutant form of RFP-p24delta5 that cannot exit the
      ER. SYP72-YFP does not colocalize with Golgi markers, except when the Golgi
      stacks are immobilized through actin depolymerization. Endogenous SYP7 SNAREs,
      also colocalize with immobilized COPII/Golgi. In contrast, XFP-tagged versions of
      plant homologs to TIP20 of the Dsl1 COPI-tethering factor complex, and the COPII
      tethering factor p115 colocalize perfectly with Golgi stacks irrespective of the
      motile status. These data suggest that COPI vesicle fusion with the ER is
      restricted to periods when Golgi stacks are stationary, but that when moving both
      COPII and COPI vesicles are tethered and collect in the ER-Golgi interface. Thus,
      the Golgi stack and an associated domain of the ER thereby constitute a mobile
      secretory and recycling unit: a unique feature in eukaryotic cells.

PMID- 22876252
TI  - Phylogenetic analysis of k(+) transporters in bryophytes, lycophytes, and
      flowering plants indicates a specialization of vascular plants.
AB  - As heritage from early evolution, potassium (K(+)) is absolutely necessary for
      all living cells. It plays significant roles as stabilizer in metabolism and is
      important for enzyme activation, stabilization of protein synthesis, and
      neutralization of negative charges on cellular molecules as proteins and nucleic
      acids. Land plants even enlarged this spectrum of K(+) utilization after having
      gone ashore, despite the fact that K(+) is far less available in their new
      oligotrophic habitats than in sea water. Inevitably, plant cells had to improve
      and to develop unique transport systems for K(+) accumulation and distribution.
      In the past two decades a manifold of K(+) transporters from flowering plants has
      been identified at the molecular level. The recently published genome of the fern
      ally Selaginella moellendorffii now helps in providing a better understanding on
      the molecular changes involved in the colonization of land and the development of
      the vasculature and the seeds. In this article we present an inventory of K(+)
      transporters of this lycophyte and pigeonhole them together with their relatives
      from the moss Physcomitrella patens, the monocotyledon Oryza sativa, and two
      dicotyledonous species, the herbaceous plant Arabidopsis thaliana, and the tree
      Populus trichocarpa. Interestingly, the transition of green plants from an
      aqueous to a dry environment coincides with a dramatic reduction in the diversity
      of voltage-gated potassium channels followed by a diversification on the basis of
      one surviving K(+) channel class. The first appearance of K(+) release (K(out))
      channels in S. moellendorffii that were shown in Arabidopsis to be involved in
      xylem loading and guard cell closure coincides with the specialization of
      vascular plants and may indicate an important adaptive step.

PMID- 22876253
TI  - Systems biology of gibberellin induced plant cell growth.

PMID- 22876254
TI  - Screening the banana biodiversity for drought tolerance: can an in vitro growth
      model and proteomics be used as a tool to discover tolerant varieties and
      understand homeostasis.
AB  - There is a great need for research aimed at understanding drought tolerance,
      screening for drought tolerant varieties and breeding crops with an improved
      water use efficiency. Bananas and plantains are a major staple food and export
      product with a worldwide production of over 135 million tonnes per year. Water
      however is the most limiting abiotic factor in banana production. A screening of
      the Musa biodiversity has not yet been performed. We at KU Leuven host the Musa
      International Germplasm collection with over 1200 accessions. To screen the Musa
      biodiversity for drought tolerant varieties, we developed a screening test for in
      vitro plants. Five varieties representing different genomic constitutions in
      banana (AAAh, AAA, AAB, AABp, and ABB) were selected and subjected to a mild
      osmotic stress. The ABB variety showed the smallest stress induced growth
      reduction. To get an insight into the acclimation and the accomplishment of
      homeostasis, the leaf proteome of this variety was characterized via 2D DIGE.
      After extraction of the leaf proteome of six control and six stressed plants,
      2600 spots could be distinguished. A PCA analysis indicates that control and
      stressed plants can blindly be classified based on their proteome. One hundred
      and twelve proteins were significantly more abundant in the stressed plants and
      18 proteins were significantly more abundant in control plants (FDR alpha 0.05).
      Twenty four differential proteins could be identified. The proteome analysis
      clearly shows that there is a new balance in the stressed plants and that the
      respiration, metabolism of ROS and several dehydrogenases involved in NAD/NADH
      homeostasis play an important role.

PMID- 22876255
TI  - Protein phosphorylation in plant immunity: insights into the regulation of
      pattern recognition receptor-mediated signaling.
AB  - Plants are continuously challenged by pathogens including viruses, bacteria, and
      fungi. The plant immune system recognizes invading pathogens and responds by
      activating an immune response. These responses occur rapidly and often involve
      post-translational modifications (PTMs) within the proteome. Protein
      phosphorylation is a common and intensively studied form of these PTMs and
      regulates many plant processes including plant growth, development, and immunity.
      Most well-characterized pattern recognition receptors (PRRs), including
      Xanthomonas resistance 21, flagellin sensitive 2, and elongation factor-Tu
      receptor, possess intrinsic protein kinase activity and regulate downstream
      signaling through phosphorylation events. Here, we focus on the phosphorylation
      events of plant PRRs that play important roles in the immune response. We also
      discuss the role of phosphorylation in regulating mitogen-associated protein
      kinase cascades and transcription factors in plant immune signaling.

PMID- 22876257
TI  - Effects of Perinuclear Chromosome Tethers in the Telomeric URA3/5FOA System
      Reflect Changes to Gene Silencing and not Nucleotide Metabolism.
AB  - Telomeres are repetitive DNA sequences that protect the ends of linear
      chromosomes. Telomeres also recruit histone deacetylase complexes that can then
      spread along chromosome arms and repress the expression of subtelomeric genes in
      a process known as telomere position effect (TPE). In the budding yeast
      Saccharomyces cerevisiae, association of telomeres with the nuclear envelope is
      thought to promote TPE by increasing the local concentration of histone
      deacetylase complexes at chromosome ends. Importantly, our understanding of TPE
      stems primarily from studies that employed marker genes inserted within yeast
      subtelomeres. In particular, the prototrophic marker URA3 is commonly used to
      assay TPE by negative selection on media supplemented with 5-fluoro-orotic acid
      (5FOA). Recent findings suggested that decreased growth on 5FOA-containing media
      may not always indicate increased expression of a telomeric URA3 reporter, but
      can rather reflect an increase in ribonucleotide reductase (RNR) function and
      nucleotide metabolism. Thus, we set out to test if the 5FOA sensitivity of
      subtelomeric URA3-harboring cells in which we deleted various factors implicated
      in perinuclear telomere tethering reflects changes to TPE and/or RNR. We report
      that RNR inhibition restores 5FOA resistance to cells lacking RNR regulatory
      factors but not any of the major telomere tethering and silencing factors,
      including Sir2, cohibin, Mps3, Heh1, and Esc1. In addition, we find that the
      disruption of tethering pathways in which these factors participate increases the
      level of URA3 transcripts originating from the telomeric reporter gene and
      abrogates silencing of subtelomeric HIS3 reporter genes without altering RNR gene
      expression. Thus, increased 5FOA sensitivity of telomeric URA3-harboring cells
      deficient in telomere tethers reflects the dysregulation of TPE but not RNR. This
      is key to understanding relationships between telomere positioning, chromatin
      silencing, and lifespan.

PMID- 22876256
TI  - Plasticity of plasma membrane compartmentalization during plant immune responses.
AB  - Plasma membranes require high levels of plasticity to modulate the perception and
      transduction of extracellular and intracellular signals. Dynamic lateral assembly
      of protein complexes combined with an independent compositional lipid patterning
      in both membrane leaflets provide cells the opportunity to decorate this
      interface with specific proteins in an organized but dynamic manner. Such ability
      to dynamically reorganize the protein content of the plasma membrane is essential
      for the regulation of processes such as polarity of transport, development, and
      microbial infection. While the plant cell wall represents the first physical and
      mostly unspecific barrier for invading microbes, the plasma membrane is at the
      forefront of microbial recognition and initiation of defense responses.
      Accumulating evidence indicating dynamic compartmentalization of plasma membranes
      in response to environmental cues has increased the interest in the compositional
      heterogeneity of this bilayer. Here, we elucidate the recruitment of specific
      proteins into defined membrane structures that ensure functional
      compartmentalization of the bilayer during infection processes.

PMID- 22876259
TI  - Mr. Harper and Child Psychiatry-I wanna get Political, Political.

PMID- 22876258
TI  - The neurobiology of sensing respiratory gases for the control of animal behavior.
AB  - Aerobic metabolism is fundamental for almost all animal life. Cellular
      consumption of oxygen (O(2)) and production of carbon dioxide (CO(2)) signal
      metabolic states and physiological stresses. These respiratory gases are also
      detected as environmental cues that can signal external food quality and the
      presence of prey, predators and mates. In both contexts, animal nervous systems
      are endowed with mechanisms for sensing O(2)/CO(2) to trigger appropriate
      behaviors and maintain homeostasis of internal O(2)/CO(2). Although different
      animal species show different behavioral responses to O(2)/CO(2), some underlying
      molecular mechanisms and pathways that function in the detection of respiratory
      gases are fundamentally similar and evolutionarily conserved. Studies of
      Caenorhabditis elegans and Drosophila melanogaster have identified roles for
      cyclic nucleotide signaling and the hypoxia inducible factor (HIF)
      transcriptional pathway in mediating behavioral responses to respiratory gases.
      Understanding how simple invertebrate nervous systems detect respiratory gases to
      control behavior might reveal general principles common to nematodes, insects and
      vertebrates that function in the molecular sensing of respiratory gases and the
      neural control of animal behaviors.

PMID- 22876260
TI  - Commentary on: "Review of the Pharmacotherapy of Irritability of Autism": A
      Skeptic's View on Second Generation Antipsychotics in Autism.

PMID- 22876261
TI  - [Not Available].
AB  - Dans cet article, nous abordons la question de l'acces a la pornographie sur
      Internet par les adolescents. Nous declinons plusieurs facettes de ces
      rencontres: la rencontre "fortuite", quand les adolescents sont confrontes a des
      images intempestives, des publicites ou spams avec des contenus pornographiques;
      la rencontre "spectatrice", quand les adolescents cherchent activement des videos
      ou photos mettant en scene la sexualite; et enfin la rencontre "actrice", quand
      les adolescents se mettent en scene eux-memes, seuls ou a plusieurs, de facon
      pornographique sur le Net. A partir d'exemple, nous reflechissons aux enjeux de
      ces rencontres virtuelles precoces de la sexualite adulte par rapport au
      developpement adolescent et a la representation de leur propre sexualite en
      construction.

PMID- 22876262
TI  - Multiple health-risk behaviour and psychological distress in adolescence.
AB  - OBJECTIVE: To examine the prevalence and correlates of psychological distress in
      a school-based sample of Canadian adolescents. METHOD: Self-reported data of
      demographics, weight status, physical activity, screen-time, diet, substance use,
      and psychological distress were derived from a representative sample of 2935
      students in grades 9 to 12 (M(age) = 15.9 years) from the 2009 Ontario Student
      Drug Use and Health Survey. RESULTS: Overall prevalence of psychological distress
      was 35.1%. Significant associations were shown between psychological distress and
      the following: being female, tobacco use, not meeting physical activity and
      screen-time recommendations, and inadequate consumption of breakfast and
      vegetables. CONCLUSIONS: These findings highlight the need for targeting greater
      physical health promotion for adolescents at risk of mental health problems.

PMID- 22876263
TI  - The effects of gender on adolescent suicide in ontario, Canada.
AB  - OBJECTIVE: Identify patterns of suicide amongst male and female adolescents aged
      11-18 years in Ontario. METHOD: All 370 adolescent suicides in Ontario between
      January 2000 and November 2006 were analyzed. Previous attempts, history of
      psychiatric treatment, location committed and method of suicide were assessed.
      Data was analyzed using 2-tailed t-tests and chi-square without Yates'
      correction. RESULTS: Male adolescent suicide was twice as common as female
      suicide. Males were more likely to use violent methods (p=0.0352) and females
      were more likely to have a history of a previous suicide attempt (p=0.0001).
      CONCLUSIONS: While most of the data agree with previous studies in adult
      populations, the ratio of male to female suicides was much lower in our
      adolescent population.

PMID- 22876264
TI  - Spirituality and Religion in Youth Suicide Attempters' Trajectories of Mental
      Health Service Utilization: The Year before a Suicide Attempt.
AB  - OBJECTIVE: Youth suicide attempters are high-risk for suicide. Many have
      untreated mental disorders and are not receiving services. It is crucial to
      understand potential influences associated with service use.
      Spirituality/religion are one influence in youths' mental health service
      trajectories. This study explored youths' experiences of spirituality/religion as
      it relates to their help-seeking the year before their suicide attempt. METHOD:
      Fifteen youth (aged 14-18) who made a suicide attempt(s) one to two years prior
      were consecutively recruited through the Depressive Disorders Program of a
      psychiatric hospital and interviewed using a mixed-methods design, including an
      adapted psychological autopsy method. RESULTS: THREE THEMES EMERGED: religious
      community members acted as a bridge, step, or provider to mental health services;
      religious/spiritual discourses were encountered within services; and many youths
      reported changes in spirituality/religious beliefs the year before their suicide
      attempt. CONCLUSIONS: Spirituality/religion can have a role in these youths'
      service trajectories. How this confers protection or challenges needs to be
      clarified. Our findings can inform policies supporting training religious leaders
      about suicide intervention to foster coordination with mental health services,
      and service-providers in judiciously approaching spiritual/religious themes in
      suicide prevention.

PMID- 22876265
TI  - Mental health problems in children with prader-willi syndrome.
AB  - BACKGROUND: Prader-Willi Syndrome (PWS) is a genetically determined
      neurodevelopmental disorder, which occurs in approximately one in 22000 births.
      AIMS: This study aimed to investigate psychiatric characteristics of children
      diagnosed with PWS compared with an age-, gender- and IQ-matched control group.
      The parents of children with PWS were assessed for psychological distress in
      comparison to the parents of the control group. Methodological limitations
      identified in previous studies were addressed in the present study. METHODS:
      Psychiatric problems were evaluated in a sample of children with genetically
      confirmed PWS and an age- and IQ-matched control group using the Child Behaviour
      Checklist 6-18. Parental psychological distress for both groups was evaluated
      with the Brief Symptom Inventory. RESULTS: Children with PWS had more severe
      somatic, social, and thought problems, and were more withdrawn-depressed in
      comparison to controls. Borderline difficulties were detected for the affective,
      somatic, and attention deficit-hyperactivity CBCL DSM-orientated subscales in the
      PWS group. Parents of PWS children, in comparison to controls, had more
      somatization, phobic anxiety, obsessive-compulsive, and anxiety problems.
      CONCLUSIONS: PWS represents a complex psychological disorder with multiple areas
      of disturbances.

PMID- 22876266
TI  - Effectiveness of Day Treatment for Disruptive Behaviour Disorders: What is the
      Long-term Clinical Outcome for Children?
AB  - OBJECTIVE: The present study investigates the clinical long-term outcomes (21/2
      to 4 years post-discharge) of children aged 12 and under with a primary diagnosis
      of a Disruptive Behaviour Disorder (DBD) who attended a short-term day treatment
      program using best-practice treatment strategies. This study compared children's
      admission, discharge, and follow-up test scores on standardized measures of
      behaviour and functioning, as rated by parents. METHOD: Measures of clinical
      symptoms in the children and parent report of stress were used. To test for
      treatment effects across time, two repeated-measures ANOVAs were calculated.
      RESULTS: There was significant treatment change across time points on measures of
      social problems, externalizing symptoms, levels of aggression, intensity of
      problems, and symptoms of ADHD. CONCLUSIONS: Children with DBD who attended a
      short-term day treatment program using best-practice treatment strategies showed
      significant improvement in their behaviour at home. These improvements were
      relatively long lasting. The current study lends support to the effectiveness of
      day treatment and the idea that severe DBD can be treated using multi-modal,
      intensive, and evidence-based treatment techniques resulting in long-term change.

PMID- 22876267
TI  - Trichotillomania, bipolar disorder and white matter hyperintensities in a six
      year old girl.
AB  - A six-year-old girl was referred to our child psychiatry outpatient clinic by the
      Pediatric Neurology Unit with a diagnosis of Attention-Deficit/Hyperactivity
      Disorder (ADHD) and trichotillomania. She had neither eyebrows nor eyelashes. The
      clinical picture was of irritability, frequent tantrums, and aggressive
      behaviour. During the following year she presented several brief episodes of
      intense mood changes, which typically started with night-time onset
      trichotillomania and sleep disturbance. The episodes lasted no longer than five
      days and recurred within one or two months. A diagnosis of pediatric bipolar
      disorder (BD) was made after the first months of clinical follow-up. An MRI
      showed focal white matter hyperintensities (WMH) in T2.

PMID- 22876268
TI  - Commentary on: Trichotillomania, Bipolar Disorder and White Matter
      Hyperintensities in a Six-Year Old Girl.

PMID- 22876269
TI  - [Not Available].

PMID- 22876270
TI  - A review of executive function deficits and pharmacological management in
      children and adolescents.
AB  - OBJECTIVE: To review both the functions and dysfunction of the executive system
      (ES) focusing on the extent of executive function (EF) deficits in most
      psychiatric disorders in children and adolescents and the possibility of such
      deficits acting as markers for pharmacological management. METHOD: A LITERATURE
      REVIEW WAS CONDUCTED USING MEDLINE, PSYCHINFO, CINAHL, PSYCHARTICLES AND PUBMED
      WITH THE FOLLOWING KEYWORDS: executive function or dysfunction, pediatric or
      children or adolescents, psychopharmacology, psychotropic medications, attention
      deficit hyperactivity disorder (ADHD), depression, obsessive compulsive disorder,
      anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders
      (ASD), fetal alcohol spectrum disorders (FASD). Due to the limited amount of
      specific information obtained for some childhood disorders, the search was
      broadened to include relevant adult literature where information was
      extrapolated. RESULTS: Abundant literature was found on the nature of the ES and
      the executive dysfunctions in most psychiatric disorders in children and
      adolescents, but not so much on the use of medication. EF deficits were found to
      be more consistent in disorders such as ADHD, ASD and FASD than in the other
      disorders but were not specific enough for use as clinical markers for those
      disorders. For children with ADHD and ASD there was adequate information on the
      use of psychotropic medications and impact on some EF domains but information on
      the impact of medication on EF in the other disorders in children and adolescents
      was fairly limited. Medications acting on the dopaminergic system also showed
      positive effects on EF deficits and are commonly used in the treatment of EF
      disorders such as ADHD, ASD and FASD. CONCLUSION: Existing literature indicates
      that EF deficits underlie most psychiatric disorders in children and adolescents.
      However, there are so many executive functions linked to so many activities and
      circuits in the brain that it is hard to quantify them in a particular disorder
      for use as specific markers for that disorder. The ES uses dopamine as its main
      neurotransmitter and this has implications for clinical management. Dopamine
      agonists (e.g. stimulants) and antagonists (e.g. neuroleptics) are medications
      that have direct impact on the ES and are commonly used to treat EF disorders in
      children and adolescents while serotonergic medications e.g. selective serotonin
      reuptake inhibitors (SSRIs) have not been very successful in treating such
      disorders. Identifying EF deficits early could be useful in guiding management
      including the use of medication in those disorders.

PMID- 22876271
TI  - Tricyclic Pyrazoles. Part 5. Novel 1,4-Dihydroindeno[1,2-c]pyrazole CB2 Ligands
      Using Molecular Hybridization Based on Scaffold Hopping.
AB  - In search of new selective CB2 ligands, the synthesis and preliminary biological
      evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazole hybrids of the highly potent
      prototypicals 5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-N-fenchyl-1H
      pyrazole-3-carboxamide 1 and 1-(2,4-dichlorophenyl)-6-methyl-N-(piperidin-1-yl)
      1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide 2 are detailed.We postulated that
      the introduction of those pharmacophoric elements essential for activity of 1 in
      the tricyclic core of 2 might provide CB2 ligands with further improved receptor
      selectivity and biological activity. Among the compounds, 6-chloro-7-methyl-1
      (2,4-dichlorophenyl)-N-fenchyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide
      (22) exhibited low two digit nanomolar affinity for the cannabinoid CB2R and
      maintained a high level of CB2-selectivity.

PMID- 22876272
TI  - Treatment of schistosomiasis in African infants and preschool-aged children:
      downward extension and biometric optimization of the current praziquantel dose
      pole.
AB  - To facilitate administration of praziquantel (PZQ) to African infants and
      preschool-aged children using a dose pole, the performance of two downwardly
      extended versions (the first created in 2010 using biometric data from Uganda
      alone and the second version created here using data from 36 countries) was
      assessed against height/weight data from a total of 166 210 preschool-aged
      children (<=6 year olds) from 36 African countries. New and optimized thresholds
      for PZQ tablet administration at one tablet (600 mg), 3/4 and 1/2 tablet
      divisions are suggested here. Both dose poles investigated estimated an
      acceptable PZQ dosage (30-60 mg/Kg) for more than 95% of children. Extension and
      optimization of the current PZQ dose pole, followed by theoretical validation
      using biometric data from preschool-aged children (0-6 years of age, 60-110 cm in
      height) from 36 African countries will help future mass drug administration
      campaigns incorporate younger children. This newly optimized dose pole with
      single 600 mg (height: 99-110 cm), 3/4 (height: 83-99 cm) and 1/2 (height: 66-83
      cm) tablet divisions, also reduces drug waste and facilitates inclusion of
      preschool-aged children. Our findings also have bearings on the use of other dose
      poles for treatment of young children. 

PMID- 22876273
TI  - Analysis of complete nucleotide sequences of 12 Gossypium chloroplast genomes:
      origin and evolution of allotetraploids.
AB  - BACKGROUND: Cotton (Gossypium spp.) is a model system for the analysis of
      polyploidization. Although ascertaining the donor species of allotetraploid
      cotton has been intensively studied, sequence comparison of Gossypium chloroplast
      genomes is still of interest to understand the mechanisms underlining the
      evolution of Gossypium allotetraploids, while it is generally accepted that the
      parents were A- and D-genome containing species. Here we performed a comparative
      analysis of 13 Gossypium chloroplast genomes, twelve of which are presented here
      for the first time. METHODOLOGY/PRINCIPAL FINDINGS: The size of 12 chloroplast
      genomes under study varied from 159,959 bp to 160,433 bp. The chromosomes were
      highly similar having >98% sequence identity. They encoded the same set of 112
      unique genes which occurred in a uniform order with only slightly different
      boundary junctions. Divergence due to indels as well as substitutions was
      examined separately for genome, coding and noncoding sequences. The genome
      divergence was estimated as 0.374% to 0.583% between allotetraploid species and A
      genome, and 0.159% to 0.454% within allotetraploids. Forty protein-coding genes
      were completely identical at the protein level, and 20 intergenic sequences were
      completely conserved. The 9 allotetraploids shared 5 insertions and 9 deletions
      in whole genome, and 7-bp substitutions in protein-coding genes. The phylogenetic
      tree confirmed a close relationship between allotetraploids and the ancestor of A
      genome, and the allotetraploids were divided into four separate groups.
      Progenitor allotetraploid cotton originated 0.43-0.68 million years ago (MYA).
      CONCLUSION: Despite high degree of conservation between the Gossypium chloroplast
      genomes, sequence variations among species could still be detected. Gossypium
      chloroplast genomes preferred for 5-bp indels and 1-3-bp indels are mainly
      attributed to the SSR polymorphisms. This study supports that the common ancestor
      of diploid A-genome species in Gossypium is the maternal source of extant
      allotetraploid species and allotetraploids have a monophyletic origin. G.
      hirsutum AD1 lineages have experienced more sequence variations than other
      allotetraploids in intergenic regions. The available complete nucleotide
      sequences of 12 Gossypium chloroplast genomes should facilitate studies to
      uncover the molecular mechanisms of compartmental co-evolution and speciation of
      Gossypium allotetraploids.

PMID- 22876274
TI  - Dissecting and circumventing the requirement for RAM in CSL-dependent Notch
      signaling.
AB  - The Notch signaling pathway is an intercellular communication network vital to
      metazoan development. Notch activation leads to the nuclear localization of the
      intracellular portion (NICD) of the Notch receptor. Once in the nucleus, NICD
      binds the transcription factor CSL through a bivalent interaction involving the
      high-affinity RAM region and the lower affinity ANK domain, converting CSL from a
      transcriptionally-repressed to an active state. This interaction is believed to
      directly displace co-repressor proteins from CSL and recruit co-activator
      proteins. Here we investigate the consequences of this bivalent organization in
      converting CSL from the repressed to active form. One proposed function of RAM is
      to promote the weak ANK:CSL interaction; thus, fusion of CSL-ANK should bypass
      this function of RAM. We find that a CSL-ANK fusion protein is transcriptionally
      active in reporter assays, but that the addition of RAM in trans further
      increases transcriptional activity, suggesting another role of RAM in activation.
      A single F235L point substitution, which disrupts co-repressor binding to CSL,
      renders the CSL-ANK fusion fully active and refractory to further stimulation by
      RAM in trans. These results suggest that in the context of a mammalian CSL-ANK
      fusion protein, the main role of RAM is to displace co-repressor proteins from
      CSL.

PMID- 22876275
TI  - Host modulators of H1N1 cytopathogenicity.
AB  - Influenza A virus infects 5-20% of the population annually, resulting in ~35,000
      deaths and significant morbidity. Current treatments include vaccines and drugs
      that target viral proteins. However, both of these approaches have limitations,
      as vaccines require yearly development and the rapid evolution of viral proteins
      gives rise to drug resistance. In consequence additional intervention strategies,
      that target host factors required for the viral life cycle, are under
      investigation. Here we employed arrayed whole-genome siRNA screening strategies
      to identify cell-autonomous molecular components that are subverted to support
      H1N1 influenza A virus infection of human bronchial epithelial cells. Integration
      across relevant public data sets exposed druggable gene products required for
      epithelial cell infection or required for viral proteins to deflect host cell
      suicide checkpoint activation. Pharmacological inhibition of representative
      targets, RGGT and CHEK1, resulted in significant protection against infection of
      human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of
      RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The
      observations reported here thus contribute to an expanding body of studies
      directed at decoding vulnerabilities in the command and control networks
      specified by influenza virulence factors.

PMID- 22876276
TI  - Assessing numerical dependence in gene expression summaries with the jackknife
      expression difference.
AB  - Statistical methods to test for differential expression traditionally assume that
      each gene's expression summaries are independent across arrays. When certain
      preprocessing methods are used to obtain those summaries, this assumption is not
      necessarily true. In general, the erroneous assumption of dependence results in a
      loss of statistical power. We introduce a diagnostic measure of numerical
      dependence for gene expression summaries from any preprocessing method and
      discuss the relative performance of several common preprocessing methods with
      respect to this measure. Some common preprocessing methods introduce non-trivial
      levels of numerical dependence. The issue of (between-array) dependence has
      received little if any attention in the literature, and researchers working with
      gene expression data should not take such properties for granted, or they risk
      unnecessarily losing statistical power.

PMID- 22876277
TI  - 6-Arylpyrido[2,3-d]pyrimidines as novel ATP-competitive inhibitors of bacterial D
      alanine:D-alanine ligase.
AB  - BACKGROUND: ATP-dependent D-alanine:D-alanine ligase (Ddl) is a part of
      biochemical machinery involved in peptidoglycan biosynthesis, as it catalyzes the
      formation of the terminal D-ala-D-ala dipeptide of the peptidoglycan precursor
      UDPMurNAc-pentapeptide. Inhibition of Ddl prevents bacterial growth, which makes
      this enzyme an attractive and viable target in the urgent search of novel
      effective antimicrobial drugs. To address the problem of a relentless increase in
      resistance to known antimicrobial agents we focused our attention to discovery of
      novel ATP-competitive inhibitors of Ddl. METHODOLOGY/PRINCIPAL FINDINGS:
      Encouraged by recent successful attempts to find selective ATP-competitive
      inhibitors of bacterial enzymes we designed, synthesized and evaluated a library
      of 6-arylpyrido[2,3-d]pyrimidine-based compounds as inhibitors of Escherichia
      coli DdlB. Inhibitor binding to the target enzyme was subsequently confirmed by
      surface plasmon resonance and studied with isothermal titration calorimetry.
      Since kinetic analysis indicated that 6-arylpyrido[2,3-d]pyrimidines compete with
      the enzyme substrate ATP, inhibitor binding to the ATP-binding site was
      additionally studied with docking. Some of these inhibitors were found to possess
      antibacterial activity against membrane-compromised and efflux pump-deficient
      strains of E. coli. CONCLUSIONS/SIGNIFICANCE: We discovered new ATP-competitive
      inhibitors of DdlB, which may serve as a starting point for development of more
      potent inhibitors of DdlB that could include both, an ATP-competitive and D-Ala
      competitive moiety.

PMID- 22876278
TI  - Integrating local and global error statistics for multi-scale RBF network
      training: an assessment on remote sensing data.
AB  - BACKGROUND: This study discusses the theoretical underpinnings of a novel multi
      scale radial basis function (MSRBF) neural network along with its application to
      classification and regression tasks in remote sensing. The novelty of the
      proposed MSRBF network relies on the integration of both local and global error
      statistics in the node selection process. METHODOLOGY AND PRINCIPAL FINDINGS: The
      method was tested on a binary classification task, detection of impervious
      surfaces using a Landsat satellite image, and a regression problem, simulation of
      waveform LiDAR data. In the classification scenario, results indicate that the
      MSRBF is superior to existing radial basis function and back propagation neural
      networks in terms of obtained classification accuracy and training-testing
      consistency, especially for smaller datasets. The latter is especially important
      as reference data acquisition is always an issue in remote sensing applications.
      In the regression case, MSRBF provided improved accuracy and consistency when
      contrasted with a multi kernel RBF network. CONCLUSION AND SIGNIFICANCE: Results
      highlight the potential of a novel training methodology that is not restricted to
      a specific algorithmic type, therefore significantly advancing machine learning
      algorithms for classification and regression tasks. The MSRBF is expected to find
      numerous applications within and outside the remote sensing field.

PMID- 22876279
TI  - Ubiquitin-associated (UBA) domain in human Fas associated factor 1 inhibits tumor
      formation by promoting Hsp70 degradation.
AB  - Human Fas associated factor 1 (hFAF1) is a pro-apoptotic scaffolding protein
      containing ubiquitin-associating (UBA), ubiquitin like 1 and 2 (UBL1, UBL2), and
      ubiquitin regulatory X (UBX) domains. hFAF1 interacts with polyubiquitinated
      proteins via its N-terminal UBA domain and with valosin containing protein (VCP)
      via its C-terminal UBX domain. Overexpression of hFAF1 or its N-terminal UBA
      domain significantly increases cell death by increasing the degradation of
      polyubiquitinated proteins. In this study, we investigated whether hFAF1, whose
      expression level is reduced in cervical cancer, plays a role in tumor formation.
      We found that HeLa cells overexpressing full-length hFAF1 or the hFAF1 UBA domain
      alone, significantly suppressed the anchorage independent tumor growth in soft
      agar colony formation, increased cell death, and activated JNK and caspase 3.
      Employing UBA-specific tandem immunoprecipitation, we identified moieties
      specifically interacting with UBA domain of hFAF1, and found that
      polyubiquitinated Hsp70s are recruited to UBA domain. We also demonstrated that
      hFAF1 overexpression promotes Hsp70 degradation via the proteasome. We further
      found that mutating the UBA domain (I41N), as well as knocking down hFAF1 with
      specific RNAi, abolishs its ability to increase the proteasomal degradation of
      Hsp70. These findings suggest that hFAF1 inhibits tumor formation by increasing
      the degradation of Hsp70 mediated via its UBA domain.

PMID- 22876280
TI  - Estimating niche width using stable isotopes in the face of habitat variability:
      a modelling case study in the marine environment.
AB  - Distributions of stable isotopes have been used to infer an organism's trophic
      niche width, the 'isotopic niche', and examine resource partitioning. Spatial
      variation in the isotopic composition of prey may however confound the
      interpretation of isotopic signatures especially when foragers exploit resources
      across numerous locations. In this study the isotopic compositions from marine
      assemblages are modelled to determine the role of variation in the signature of
      prey items and the effect of dietary breadth and foraging strategies on predator
      signatures. Outputs from the models reveal that isotopic niche widths can be
      greater for populations of dietary specialists rather than for generalists, which
      contravenes what is generally accepted in the literature. When a range of
      different mixing models are applied to determine if the conversion from delta to
      p-space can be used to improve model accuracy, predator signature variation is
      increased rather than model precision. Furthermore the mixing models applied
      failed to correctly identify dietary specialists and/or to accurately estimate
      diet contributions that may identify resource partitioning. The results presented
      illustrate the need to collect sufficiently large sample sizes, in excess of what
      is collected under most current studies, across the complete distribution of a
      species and its prey, before attempts to use stable isotopes to make inferences
      about niche width can be made.

PMID- 22876281
TI  - Electrophysiological correlates of binocular stereo depth without binocular
      disparities.
AB  - A small region of background presented to only one eye in an otherwise binocular
      display may, under certain conditions, be resolved in the visual system by
      interpreting the region as a small gap between two similar objects placed at
      different depths, with the gap hidden in one eye by parallax. This has been
      called monocular gap stereopsis. We investigated the electrophysiological
      correlate of this type of stereopsis by means of sum potential recordings in 12
      observers, comparing VEP's for this stimulus ("Gillam Stereo", Author BG has
      strong reservations about this term) with those for similar stimuli containing
      disparity based depth and with no depth (flat). In addition we included several
      control stimuli. The results show a pronounced early negative potential at a
      latency of around 170 ms (N170) for all stimuli containing non- identical
      elements, be they a difference caused by binocular disparity or by completely
      unmatched monocular contours. A second negative potential with latency around 270
      ms (N270), on the other hand, is present only with stimuli leading to fusion and
      the perception of depth. This second component is similar for disparity-based
      stereopsis and monocular gap, or "Gillam Stereo" although slightly more
      pronounced for the former. We conjecture that the first component is related to
      the detection of differences between the images of the two eyes that may then
      either be fused, leading to stereopsis and the corresponding second potential, or
      else to inhibition and rivalry without a later trace in the VEP. The finding that
      that "Gillam Stereo" leads to cortical responses at the same short latencies as
      disparity based stereopsis indicates that it may partly rely on quite early
      cortical mechanisms.

PMID- 22876282
TI  - Spottier targets are less attractive to tabanid flies: on the tabanid-repellency
      of spotty fur patterns.
AB  - During blood-sucking, female members of the family Tabanidae transmit pathogens
      of serious diseases and annoy their host animals so strongly that they cannot
      graze, thus the health of the hosts is drastically reduced. Consequently, a
      tabanid-resistant coat with appropriate brightness, colour and pattern is
      advantageous for the host. Spotty coats are widespread among mammals, especially
      in cattle (Bos primigenius). In field experiments we studied the influence of the
      size and number of spots on the attractiveness of test surfaces to tabanids that
      are attracted to linearly polarized light. We measured the reflection
      polarization characteristics of living cattle, spotty cattle coats and the used
      test surfaces. We show here that the smaller and the more numerous the spots, the
      less attractive the target (host) is to tabanids. We demonstrate that the
      attractiveness of spotty patterns to tabanids is also reduced if the target
      exhibits spottiness only in the angle of polarization pattern, while being
      homogeneous grey with a constant high degree of polarization. Tabanid flies
      respond strongly to linearly polarized light, and we show that bright and dark
      parts of cattle coats reflect light with different degrees and angles of
      polarization that in combination with dark spots on a bright coat surface disrupt
      the attractiveness to tabanids. This could be one of the possible evolutionary
      benefits that explains why spotty coat patterns are so widespread in mammals,
      especially in ungulates, many species of which are tabanid hosts.

PMID- 22876283
TI  - How to design a targeted agricultural subsidy system: efficiency or equity?
AB  - In this paper we appraise current agricultural subsidy policy in the EU. Several
      sources of its inefficiency are identified: it is inefficient for supporting
      farmers' incomes or guaranteeing food security, and irrational transfer payments
      decoupled from actual performance that may be negative for environmental
      protection, social cohesion, etc. Based on a simplified economic model, we prove
      that there is "reverse redistribution" in the current tax-subsidy system, which
      cannot be avoided. To find a possible way to distribute subsidies more
      efficiently and equitably, several alternative subsidy systems (the pure loan,
      the harvest tax and the income contingent loan) are presented and examined.

PMID- 22876284
TI  - Construction of a genetic linkage map and genetic analysis of domestication
      related traits in mungbean (Vigna radiata).
AB  - The genetic differences between mungbean and its presumed wild ancestor were
      analyzed for domestication related traits by QTL mapping. A genetic linkage map
      of mungbean was constructed using 430 SSR and EST-SSR markers from mungbean and
      its related species, and all these markers were mapped onto 11 linkage groups
      spanning a total of 727.6 cM. The present mungbean map is the first map where the
      number of linkage groups coincided with the haploid chromosome number of
      mungbean. In total 105 QTLs and genes for 38 domestication related traits were
      identified. Compared with the situation in other Vigna crops, many linkage groups
      have played an important role in the domestication of mungbean. In particular the
      QTLs with high contribution were distributed on seven out of 11 linkage groups.
      In addition, a large number of QTLs with small contribution were found. The
      accumulation of many mutations with large and/or small contribution has
      contributed to the differentiation between wild and cultivated mungbean. The
      useful QTLs for seed size, pod dehiscence and pod maturity that have not been
      found in other Asian Vigna species were identified in mungbean, and these QTLs
      may play the important role as new gene resources for other Asian Vigna species.
      The results provide the foundation that will be useful for improvement of
      mungbean and related legumes.

PMID- 22876285
TI  - Changes in the Staphylococcus aureus transcriptome during early adaptation to the
      lung.
AB  - Staphylococcus aureus is a common inhabitant of the human nasopharynx. It is also
      a cause of life-threatening illness, producing a potent array of virulence
      factors that enable survival in normally sterile sites. The transformation of S.
      aureus from commensal to pathogen is poorly understood. We analyzed S. aureus
      gene expression during adaptation to the lung using a mouse model of S. aureus
      pneumonia. Bacteria were isolated by bronchoalveolar lavage after residence in
      vivo for up to 6 hours. S. aureus in vivo RNA transcription was compared by
      microarray to that of shake flask grown stationary phase and early exponential
      phase cells. Compared to in vitro conditions, the in vivo transcriptome was
      dramatically altered within 30 minutes. Expression of central metabolic pathways
      changed significantly in response to the lung environment. Gluconeogenesis (fbs,
      pckA) was down regulated, as was TCA cycle and fermentation pathway gene
      expression. Genes associated with amino acid synthesis, RNA translation and
      nitrate respiration were upregulated, indicative of a highly active metabolic
      state during the first 6 hours in the lung. Virulence factors regulated by agr
      were down regulated in vivo and in early exponential phase compared to stationary
      phase cells. Over time in vivo, expression of ahpCF, involved in H(2)O(2)
      scavenging, and uspA, which encodes a universal stress regulator, increased.
      Transcription of leukotoxic alpha and beta-type phenol-soluble modulins psmalpha1
      4 and psmbeta1-2 increased 13 and 8-fold respectively; hld mRNA, encoding delta
      hemolysin, was increased 9-fold. These were the only toxins to be significantly
      upregulated in vivo. These data provide the first complete survey of the S.
      aureus transcriptome response to the mammalian airway. The results present
      intriguing contrasts with previous work in other in vitro and in vivo models and
      provide novel insights into the adaptive and temporal response of S. aureus early
      in the pathogenesis of pneumonia.

PMID- 22876286
TI  - Reactive oxygen species regulate protrusion efficiency by controlling actin
      dynamics.
AB  - Productive protrusions allowing motile cells to sense and migrate toward a
      chemotactic gradient of reactive oxygen species (ROS) require a tight control of
      the actin cytoskeleton. However, the mechanisms of how ROS affect cell protrusion
      and actin dynamics are not well elucidated yet. We show here that ROS induce the
      formation of a persistent protrusion. In migrating epithelial cells, protrusion
      of the leading edge requires the precise regulation of the lamellipodium and
      lamella F-actin networks. Using fluorescent speckle microscopy, we showed that,
      upon ROS stimulation, the F-actin retrograde flow is enhanced in the
      lamellipodium. This event coincides with an increase of cofilin activity, free
      barbed ends formation, Arp2/3 recruitment, and ERK activity at the cell edge. In
      addition, we observed an acceleration of the F-actin flow in the lamella of ROS
      stimulated cells, which correlates with an enhancement of the cell contractility.
      Thus, this study demonstrates that ROS modulate both the lamellipodium and the
      lamella networks to control protrusion efficiency.

PMID- 22876287
TI  - Molecular characterization of pathogenic members of the genus Fonsecaea using
      multilocus analysis.
AB  - Members of the fungal genus Fonsecaea causing human chromoblastomycosis show
      substantial geographic structuring. Genetic identity of clinical and
      environmental strains suggests transmission from plant debris, while the
      evolutionary processes that have led to spatially separated populations have
      remained unexplained. Sequences of ITS, BT2, ACT1, Cdc42, Lac and HmgA were
      analyzed, either by direct sequencing or by cloning. Thirty-seven clinical and
      environmental Fonsecaea strains from Central and South America, Asia, Africa and
      Europe were sequenced and possible recombination events were calculated.
      Phylogenetic trees of Cdc42, Lac and HmgA were statistically supported, but ITS,
      BT2 and ACT1 trees were not. The Standardized Index of Association (I(A) (S)) did
      not detect recombination (I(A) (S) = 0.4778), neither did the Phi-test for
      separate genes. In Fonsecaea nubica non-synonymous mutations causing functional
      changes were observed in Lac gene, even though no selection pressures were
      detected with the neutrality test (Tajima D test, p>0.05). Genetic
      differentiation of populations for each gene showed separation of American,
      African and Asian populations. Strains of clinical vs. environmental origin
      showed genetic distances that were comparable or lower than found in geographic
      differentiation. In conclusion, here we demonstrated clonality of sibling species
      using multilocus data, geographic structuring of populations, and a low
      functional and structural selective constraint during evolution of the genus
      Fonsecaea.

PMID- 22876288
TI  - MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast
      cancer cells via targeting FAK expression.
AB  - Focal adhesion kinase (FAK) is an important mediator of extracellular matrix
      integrin signaling, cell motility, cell proliferation and cell survival.
      Increased FAK expression is observed in a variety of solid human tumors and
      increased FAK expression and activity frequently correlate with metastatic
      disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK
      expression. miR-7 expression is decreased in malignant versus normal breast
      tissue and its expression correlates inversely with metastasis in human breast
      cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and
      decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels
      of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively
      correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression
      of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer
      proliferation, anchorage independent growth, three-dimensional growth in
      Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100
      mammary epithelial cell line promoted cell proliferation and anchorage
      independent growth. Rescue of FAK expression reversed miR-7 suppression of
      migration and invasion. miR-7 also inhibited primary breast tumor development,
      local invasion and metastatic colonization of breast cancer xenografts. Thus, miR
      7 expression is decreased in metastatic breast cancer, correlates with the level
      of epithelial differentiation of the tumor and inhibits metastatic progression.

PMID- 22876289
TI  - Isolation and characterization of functional tripartite group II introns using a
      Tn5-based genetic screen.
AB  - BACKGROUND: Group II introns are RNA enzymes that splice themselves from pre-mRNA
      transcripts. Most bacterial group II introns harbour an open reading frame (ORF),
      coding for a protein with reverse transcriptase, maturase and occasionally DNA
      binding and endonuclease activities. Some ORF-containing group II introns were
      shown to be mobile retroelements that invade new DNA target sites. From an
      evolutionary perspective, group II introns are hypothesized to be the ancestors
      of the spliceosome-dependent nuclear introns and the small nuclear RNAs (snRNAs-
      U1, U2, U4, U5 and U6) that are important functional elements of the spliceosome
      machinery. The ability of some group II introns fragmented in two or three pieces
      to assemble and undergo splicing in trans supports the theory that spliceosomal
      snRNAs evolved from portions of group II introns. METHODOLOGY/PRINCIPAL FINDINGS:
      We used a transposon-based genetic screen to explore the ability of the Ll.LtrB
      group II intron from the Gram-positive bacterium Lactococcus lactis to be
      fragmented into three pieces in vivo. Trans-splicing tripartite variants of
      Ll.LtrB were selected using a highly efficient and sensitive trans
      splicing/conjugation screen. We report that numerous fragmentation sites located
      throughout Ll.LtrB support tripartite trans-splicing, showing that this intron is
      remarkably tolerant to fragmentation. CONCLUSIONS/SIGNIFICANCE: This work unveils
      the great versatility of group II intron fragments to assemble and accurately
      trans-splice their flanking exons in vivo. The selected introns represent the
      first evidence of functional tripartite group II introns in bacteria and provide
      experimental support for the proposed evolutionary relationship between group II
      introns and snRNAs.

PMID- 22876291
TI  - The effect of urbanization on ant abundance and diversity: a temporal examination
      of factors affecting biodiversity.
AB  - Numerous studies have examined the effect of urbanization on species richness and
      most studies implicate urbanization as the major cause of biodiversity loss.
      However, no study has identified an explicit connection between urbanization and
      biodiversity loss as the impact of urbanization is typically inferred indirectly
      by comparing species diversity along urban-rural gradients at a single time
      point. A different approach is to focus on the temporal rather than the spatial
      aspect and perform "before and after" studies where species diversity is
      cataloged over time in the same sites. The current study examined changes in ant
      abundance and diversity associated with the conversion of natural habitats into
      urban habitats. Ant abundance and diversity were tracked in forested sites that
      became urbanized through construction and were examined at 3 time points -
      before, during, and after construction. On average, 4.3 +/- 1.2 unique species
      were detected in undisturbed plots prior to construction. Ant diversity decreased
      to 0.7 +/- 0.8 species in plots undergoing construction and 1.5 +/- 1.1 species
      in plots 1 year after construction was completed. With regard to species
      richness, urbanization resulted in the permanent loss of 17 of the 20 species
      initially present in the study plots. Recovery was slow and only 3 species were
      present right after construction was completed and 4 species were present 1 year
      after construction was completed. The second objective examined ant fauna
      recovery in developed residential lots based on time since construction,
      neighboring habitat quality, pesticide inputs, and the presence of invasive ants.
      Ant diversity was positively correlated with factors that promoted ecological
      recovery and negatively correlated with factors that promoted ecological
      degradation. Taken together, these results address a critical gap in our
      knowledge by characterizing the short- and long-term the effects of urbanization
      on the loss of ant biodiversity.

PMID- 22876290
TI  - Calcineurin regulates homologous desensitization of natriuretic peptide receptor
      A and inhibits ANP-induced testosterone production in MA-10 cells.
AB  - Receptor desensitization is a ubiquitous regulatory mechanism that defines the
      activatable pool of receptors, and thus, the ability of cells to respond to
      environmental stimuli. In recent years, the molecular mechanisms controlling the
      desensitization of a variety of receptors have been established. However, little
      is known about the molecular mechanisms that underlie desensitization of
      natriuretic peptide receptors, including natriuretic peptide receptor-A (NPR-A).
      Here we report that calcineurin (protein phosphatase 2B, PP2B, PPP3C) regulates
      homologous desensitization of NPR-A in murine Leydig tumor (MA-10) cells. We
      demonstrate that both pharmacological inhibition of calcineurin activity and
      siRNA-mediated suppression of calcineurin expression potentiate atrial
      natriuretic peptide (ANP)-induced cGMP synthesis. Treatment of MA-10 cells with
      inhibitors of other phosphoprotein phosphatases had little or no effect on ANP
      induced cGMP accumulation. In addition, overexpression of calcineurin blunts ANP
      induced cGMP synthesis. We also present data indicating that the inhibition of
      calcineurin potentiates ANP-induced testosterone production. To better understand
      the contribution of calcineurin in the regulation of NPR-A activity, we examined
      the kinetics of ANP-induced cGMP signals. We observed transient ANP-induced cGMP
      signals, even in the presence of phosphodiesterase inhibitors. Inhibition of both
      calcineurin and phosphodiesterase dramatically slowed the decay in the response.
      These observations are consistent with a model in which calcineurin mediated
      dephosphorylation and desensitization of NPR-A is associated with significant
      inhibition of cGMP synthesis. PDE activity hydrolyzes cGMP, thus lowering
      intracellular cGMP toward the basal level. Taken together, these data suggest
      that calcineurin plays a previously unrecognized role in the desensitization of
      NPR-A and, thereby, inhibits ANP-mediated increases in testosterone production.

PMID- 22876293
TI  - Anaemia, haemoglobin level and cause-specific mortality in people with and
      without diabetes.
AB  - BACKGROUND: Both anaemia and cardiovascular disease (CVD) are common in people
      with diabetes. While individually both characteristics are known to raise
      mortality risk, their combined influence has yet to be quantified. In this
      pooling project, we examined the combined impact of baseline haemoglobin levels
      and existing CVD on all-cause and CVD mortality in people with diabetes. We draw
      comparison of these effects with those apparent in diabetes-free individuals.
      METHODS/PRINCIPAL FINDINGS: A combined analyses of 7 UK population-based cohorts
      resulted in 26,480 study members. There were 946 participants with physician
      diagnosed diabetes, 2227 with anaemia [haemoglobin<13 g/dl (men) or <12 (women)],
      2592 with existing CVD (stroke, ischaemic heart disease), and 21,396 with none of
      the conditions. Across diabetes and anaemia subgroups, and using diabetes-free,
      non-anaemic participants as the referent group, the adjusted hazard ratios (HR)
      were 1.46 (95% CI: 1.30-1.63) for anaemia, 1.67 (1.45-1.92) for diabetes, and
      2.10 (1.55-2.85) for diabetes and anaemia combined. Across combined diabetes,
      anaemia and CVD subgroups, and compared with non-anaemic, diabetes-free and CVD
      free participants, HR (95% CI) for all-cause mortality were 1.49 (1.32-1.69)
      anaemia, 1.60 (1.46-1.76) for existing CVD, and 1.66 (1.39-1.97) for diabetes
      alone. Equivalents were 2.13 (1.48-3.07) for anaemia and diabetes, 2.68 (2.14
      3.36) for diabetes and existing CVD, and 3.25 (1.88-5.62) for the three combined.
      Patterns were similar for CVD mortality. CONCLUSIONS/SIGNIFICANCE: Individually,
      anaemia and CVD confer similar mortality risks in people with diabetes, and are
      excessively fatal in combination. Screening for anaemia would identify vulnerable
      diabetic patients whose outcomes can potentially be improved.

PMID- 22876294
TI  - An induced pocket for the binding of potent fusion inhibitor CL-385319 with H5N1
      influenza virus hemagglutinin.
AB  - The influenza glycoprotein hemagglutinin (HA) plays crucial roles in the early
      stage of virus infection, including receptor binding and membrane fusion.
      Therefore, HA is a potential target for developing anti-influenza drugs.
      Recently, we characterized a novel inhibitor of highly pathogenic H5N1 influenza
      virus, CL-385319, which specifically inhibits HA-mediated viral entry. Studies
      presented here identified the critical binding residues for CL-385319, which
      clustered in the stem region of the HA trimer by site-directed mutagenesis.
      Extensive computational simulations, including molecular docking, molecular
      dynamics simulations, molecular mechanics generalized Born surface area (MM_GBSA)
      calculations, charge density and Laplacian calculations, have been carried out to
      uncover the detailed molecular mechanism that underlies the binding of CL-385319
      to H5N1 influenza virus HA. It was found that the recognition and binding of CL
      385319 to HA proceeds by a process of "induced fit" whereby the binding pocket is
      formed during their interaction. Occupation of this pocket by CL-385319
      stabilizes the neutral pH structure of hemagglutinin, thus inhibiting the
      conformational rearrangements required for membrane fusion. This "induced fit"
      pocket may be a target for structure-based design of more potent influenza fusion
      inhibitors.

PMID- 22876295
TI  - A new estimation of global soil greenhouse gas fluxes using a simple data
      oriented model.
AB  - Soil greenhouse gas fluxes (particularly CO(2), CH(4), and N(2)O) play important
      roles in climate change. However, despite the importance of these soil greenhouse
      gases, the number of reports on global soil greenhouse gas fluxes is limited.
      Here, new estimates are presented for global soil CO(2) emission (total soil
      respiration), CH(4) uptake, and N(2)O emission fluxes, using a simple data
      oriented model. The estimated global fluxes for CO(2) emission, CH(4) uptake, and
      N(2)O emission were 78 Pg C yr(-1) (Monte Carlo 95% confidence interval, 64-95 Pg
      C yr(-1)), 18 Tg C yr(-1) (11-23 Tg C yr(-1)), and 4.4 Tg N yr(-1) (1.4-11.1 Tg N
      yr(-1)), respectively. Tropical regions were the largest contributor of all of
      the gases, particularly the CO(2) and N(2)O fluxes. The soil CO(2) and N(2)O
      fluxes had more pronounced seasonal patterns than the soil CH(4) flux. The
      collected estimates, including both the previous and the present estimates,
      demonstrate that the means of the best estimates from each study were 79 Pg C yr(
      1) (291 Pg CO(2) yr(-1); coefficient of variation, CV = 13%, N = 6) for CO(2), 21
      Tg C yr(-1) (29 Tg CH(4) yr(-1); CV = 24%, N = 24) for CH(4), and 7.8 Tg N yr(-1)
      (12.2 Tg N(2)O yr(-1); CV = 38%, N = 11) for N(2)O. For N(2)O, the mean of the
      estimates that was calculated by excluding the earliest two estimates was 6.6 Tg
      N yr(-1) (10.4 Tg N(2)O yr(-1); CV = 22%, N = 9). The reported estimates vary and
      have large degrees of uncertainty but their overall magnitudes are in general
      agreement. To further minimize the uncertainty of soil greenhouse gas flux
      estimates, it is necessary to build global databases and identify key processes
      in describing global soil greenhouse gas fluxes.

PMID- 22876296
TI  - Effectiveness and cost-effectiveness of antidepressants in primary care: a
      multiple treatment comparison meta-analysis and cost-effectiveness model.
AB  - OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time
      horizon of pharmacological first line treatment in primary care for patients with
      moderate to severe depression. DESIGN: A multiple treatment comparison meta
      analysis was employed to determine the relative efficacy in terms of remission of
      10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine
      mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine). The estimated
      remission rates were then applied in a decision-analytic model in order to
      estimate costs and quality of life with different treatments at one year. DATA
      SOURCES: Meta-analyses of remission rates from randomised controlled trials, and
      cost and quality-of-life data from published sources. RESULTS: The most
      favourable pharmacological treatment in terms of remission was escitalopram with
      an 8- to 12-week probability of remission of 0.47. Despite a high acquisition
      cost, this clinical effectiveness translated into escitalopram being both more
      effective and having a lower total cost than all other comparators from a
      societal perspective. From a healthcare perspective, the cost per QALY of
      escitalopram was ?3732 compared with venlafaxine. CONCLUSION: Of the investigated
      antidepressants, escitalopram has the highest probability of remission and is the
      most effective and cost-effective pharmacological treatment in a primary care
      setting, when evaluated over a one year time-horizon. Small differences in
      remission rates may be important when assessing costs and cost-effectiveness of
      antidepressants.

PMID- 22876292
TI  - Hypothesis-based analysis of gene-gene interactions and risk of myocardial
      infarction.
AB  - The genetic loci that have been found by genome-wide association studies to
      modulate risk of coronary heart disease explain only a fraction of its total
      variance, and gene-gene interactions have been proposed as a potential source of
      the remaining heritability. Given the potentially large testing burden, we sought
      to enrich our search space with real interactions by analyzing variants that may
      be more likely to interact on the basis of two distinct hypotheses: a biological
      hypothesis, under which MI risk is modulated by interactions between variants
      that are known to be relevant for its risk factors; and a statistical hypothesis,
      under which interacting variants individually show weak marginal association with
      MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction
      (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP
      interaction testing using a logistic regression framework. Despite having
      reasonable power to detect interaction effects of plausible magnitudes, we
      observed no statistically significant evidence of interaction under these
      hypotheses, and no clear consistency between the top results in our discovery
      sample and those in a large validation sample of 1,766 cases of coronary heart
      disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our
      results do not support the existence of strong interaction effects as a common
      risk factor for MI. Within the scope of the hypotheses we have explored, this
      study places a modest upper limit on the magnitude that epistatic risk effects
      are likely to have at the population level (odds ratio for MI risk 1.3-2.0,
      depending on allele frequency and interaction model).

PMID- 22876297
TI  - Aromatase inhibition attenuates desflurane-induced preconditioning against acute
      myocardial infarction in male mouse heart in vivo.
AB  - The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size
      following experimental ischemia/reperfusion injury in the mouse heart. We
      hypothesized that endogenous estrogens play a role as mediators of desflurane
      induced preconditioning against myocardial infarction. In this study, we tested
      the hypothesis that desflurane effects local estrogen synthesis by modulating
      enzyme aromatase expression and activity in the mouse heart. Aromatase
      metabolizes testosterone to 17beta- estradiol (E2) and thereby significantly
      contributes to local estrogen synthesis. We tested aromatase effects in acute
      myocardial infarction model in male mice. The animals were randomized and
      subjected to four groups which were pre-treated with the selective aromatase
      inhibitor anastrozole (A group) and DES alone (DES group) or in combination
      (A+DES group) for 15 minutes prior to surgical intervention whereas the control
      group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes
      ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced
      preconditioning and increased infarct size compared to DES alone (37.94 +/- 15.5%
      vs. 17.1 +/- 3.62%) without affecting area at risk and systemic hemodynamic
      parameters following ischemia/reperfusion. Protein localization studies revealed
      that aromatase was abundant in the murine cardiovascular system with the highest
      expression levels in endothelial and smooth muscle cells. Desflurane application
      at pharmacological concentrations efficiently upregulated aromatase expression in
      vivo and in vitro. We conclude that desflurane efficiently regulates aromatase
      expression and activity which might lead to increased local estrogen synthesis
      and thus preserve cellular integrity and reduce cardiac damage in an acute
      myocardial infarction model.

PMID- 22876298
TI  - SCN5A mutations in Brugada syndrome are associated with increased cardiac
      dimensions and reduced contractility.
AB  - BACKGROUND: The cardiac sodium channel (Na(v)1.5) controls cardiac excitability.
      Accordingly, SCN5A mutations that result in loss-of-function of Na(v)1.5 are
      associated with various inherited arrhythmia syndromes that revolve around
      reduced cardiac excitability, most notably Brugada syndrome (BrS). Experimental
      studies have indicated that Na(v)1.5 interacts with the cytoskeleton and may also
      be involved in maintaining structural integrity of the heart. We aimed to
      determine whether clinical evidence may be obtained that Na(v)1.5 is involved in
      maintaining cardiac structural integrity. METHODS: Using cardiac magnetic
      resonance (CMR) imaging, we compared right ventricular (RV) and left ventricular
      (LV) dimensions and ejection fractions between 40 BrS patients with SCN5A
      mutations (SCN5a-mut-positive) and 98 BrS patients without SCN5A mutations (SCN5a
      mut-negative). We also studied 18 age/sex-matched healthy volunteers. RESULTS:
      SCN5a-mut-positive patients had significantly larger end-diastolic and end
      systolic RV and LV volumes, and lower LV ejection fractions, than SCN5a-mut
      negative patients or volunteers. CONCLUSIONS: Loss-of-function SCN5A mutations
      are associated with dilatation and impairment in contractile function of both
      ventricles that can be detected by CMR analysis.

PMID- 22876299
TI  - Incidence of pleural recurrence after computed tomography-guided needle biopsy in
      stage I lung cancer.
AB  - OBJECTIVE: A risk of tumor seeding after percutaneous needle biopsy has been
      reported in various organs, including the lung. This study retrospectively
      evaluated the proportion of ipsilateral pleural recurrence after computed
      tomography-guided needle biopsy (CTNB) in p-stage I lung cancer patients.
      METHODS: Of the 321 patients diagnosed with p-stage I lung cancer, 124 underwent
      CTNB before surgery, while 197 underwent non-CTNB procedures, including
      bronchoscopic biopsy in 188 patients and thoracoscopic wedge resection in 9.
      These patients were retrospectively analyzed. RESULTS: While the tumor size was
      significantly larger in the non-CTNB group (25 +/- 9 mm) in comparison to the
      CTNB group (19 +/- 9 mm) (p<0.001), percentage of pleural, vascular, or lymphatic
      invasions were comparable between the two groups. Eight patients developed
      ipsilateral pleural recurrences, one (1%) in the CTNB group, and 7 (4%) in the
      non-CTNB group. Of these, 3 patients developed pleural recurrence only at first,
      1 (1%) in the CTNB group, and 2 (1%) in the non-CTNB group. The differences in
      the proportions of these pleural recurrences between the 2 groups were not
      significant. Subgroup analyses by baseline characteristics such as tumor size, pT
      stage, or microscopic pleural invasion, showed that proportions of pleural
      recurrences in CTNB group were not high compared with non-CTNB group in each
      subgroup. Analysis of progression-free survival showed that recurrences in CTNB
      were not high compared with non-CTNB. CONCLUSIONS: The pleural recurrence was not
      significantly increased after CTNB in p-stage I lung cancer patients in this
      particular study.

PMID- 22876300
TI  - 13C NMR reveals no evidence of n-pi* interactions in proteins.
AB  - An n = pi* interaction between neighboring carbonyl groups has been postulated to
      stabilize protein structures. Such an interaction would affect the (13)C chemical
      shielding of the carbonyl groups, whose paramagnetic component is dominated by n
      = pi* and pi = pi* excitations. Model compound calculations indicate that both
      the interaction energetics and the chemical shielding of the carbonyl group are
      instead dominated by a classical dipole-dipole interaction. A set of high
      resolution protein structures with associated carbonyl (13)C chemical shift
      assignments verifies this correlation and provides no evidence for an inter
      carbonyl n = pi* interaction.

PMID- 22876301
TI  - Identification of novel deregulated RNA metabolism-related genes in non-small
      cell lung cancer.
AB  - Lung cancer is a leading cause of cancer death worldwide. Several alterations in
      RNA metabolism have been found in lung cancer cells; this suggests that RNA
      metabolism-related molecules are involved in the development of this pathology.
      In this study, we searched for RNA metabolism-related genes that exhibit
      different expression levels between normal and tumor lung tissues. We identified
      eight genes differentially expressed in lung adenocarcinoma microarray datasets.
      Of these, seven were up-regulated whereas one was down-regulated. Interestingly,
      most of these genes had not previously been associated with lung cancer. These
      genes play diverse roles in mRNA metabolism: three are associated with the
      spliceosome (ASCL3L1, SNRPB and SNRPE), whereas others participate in RNA-related
      processes such as translation (MARS and MRPL3), mRNA stability (PCBPC1), mRNA
      transport (RAE), or mRNA editing (ADAR2, also known as ADARB1). Moreover, we
      found a high incidence of loss of heterozygosity at chromosome 21q22.3, where the
      ADAR2 locus is located, in NSCLC cell lines and primary tissues, suggesting that
      the downregulation of ADAR2 in lung cancer is associated with specific genetic
      losses. Finally, in a series of adenocarcinoma patients, the expression of five
      of the deregulated genes (ADAR2, MARS, RAE, SNRPB and SNRPE) correlated with
      prognosis. Taken together, these results support the hypothesis that changes in
      RNA metabolism are involved in the pathogenesis of lung cancer, and identify new
      potential targets for the treatment of this disease.

PMID- 22876302
TI  - Mountain building triggered late cretaceous North American megaherbivore dinosaur
      radiation.
AB  - Prior studies of Mesozoic biodiversity document a diversity peak for dinosaur
      species in the Campanian stage of the Late Cretaceous, yet have failed to provide
      explicit causal mechanisms. We provide evidence that a marked increase in North
      American dinosaur biodiversity can be attributed to dynamic orogenic episodes
      within the Western Interior Basin (WIB). Detailed fossil occurrences document an
      association between the shift from Sevier-style, latitudinally arrayed basins to
      smaller Laramide-style, longitudinally arrayed basins and a well substantiated
      decreased geographic range/increased taxonomic diversity of megaherbivorous
      dinosaur species. Dispersal-vicariance analysis demonstrates that the nearly
      identical biogeographic histories of the megaherbivorous dinosaur clades
      Ceratopsidae and Hadrosauridae are attributable to rapid diversification events
      within restricted basins and that isolation events are contemporaneous with known
      tectonic activity in the region. SymmeTREE analysis indicates that
      megaherbivorous dinosaur clades exhibited significant variation in
      diversification rates throughout the Late Cretaceous. Phylogenetic divergence
      estimates of fossil clades offer a new lower boundary on Laramide surficial
      deformation that precedes estimates based on sedimentological data alone.

PMID- 22876303
TI  - Forced expression of miR-143 represses ERK5/c-Myc and p68/p72 signaling in
      concert with miR-145 in gut tumors of Apc(Min) mice.
AB  - Recently, miR-143 and miR-145 have been shown to belong to a subset of microRNAs
      whose expression is controlled by a complex of a tumor suppressor p53 and DEAD
      box RNA helicase subunits p68/p72. While accumulating studies have acknowledged
      that both miRNAs function as tumor suppressors and are similarly regulated,
      evidence of their coordinated action against tumorigenesis has been poorly
      presented. Herein, we establish transgenic mice that express miR-143 under the
      control of the CAG regulatory unit. When crossbred with Apc(Min/+) mice, the
      development of tumors in the small intestines is significantly attenuated. In the
      transgenic small intestine tumors, the endogenous miR-145 is also enhanced and
      the expression of c-Myc and p68/p72, both of which have been reported to be
      pivotal for gut tumor development, is suppressed, corresponding to the
      downregulation of ERK5. We demonstrate that the combination of miR-143 and miR
      145 inhibits the expression of c-Myc in human colon cancer cells, whereas miR-145
      retards that of p72. Moreover, we show the possibilities that miR-145 modulates
      p72 expression through its 3' untranslated region and that c-Myc downregulation
      is involved in both p68 suppression and miR-145 induction. These findings suggest
      that forced expression of miR-143, probably interacting with endogenous miR-145,
      inhibits ERK5/c-Myc and p68/p72/beta-catenin signaling and hampers small
      intestine tumor development in Apc(Min/+) mice. This unique cascade, in turn, may
      prevent overproduction of a subset of tumor suppressive miRNAs by repressing
      their own modulators, p68/p72.

PMID- 22876304
TI  - Effectiveness of family meetings for family caregivers on delaying time to
      nursing home placement of dementia patients: a randomized trial.
AB  - BACKGROUND: Interventions relieving the burden of caregiving may postpone or
      prevent patient institutionalization. The objective of this study was to
      determine whether a family meetings intervention was superior to usual care in
      postponing nursing home placement of patients with dementia. METHODS: A
      randomized multicenter trial was conducted among 192 patients with a clinical
      diagnosis of dementia living at home at enrolment and their primary family
      caregiver. Dyads of caregivers and patients were randomized to the family
      meetings intervention (n = 96) or usual care (n = 96) condition. The intervention
      consisted of two individual sessions with the primary caregiver and four family
      counseling sessions that included family members and friends. The primary outcome
      measure was the time until institutionalization of the patient. Intention-to
      treat as well as per protocol analyses were performed. Survival analyses were
      carried out to evaluate the effectiveness of the intervention. RESULTS: During 18
      months follow-up 23 of 96 relatives with dementia of caregivers in the
      intervention group and 18 of 96 relatives with dementia of caregivers in the
      usual care group were institutionalized. No significant difference between the
      intervention and the usual care group was found in time until
      institutionalization (adjusted hazard ratio (HR) 1.46, 95% confidence interval
      (CI) 0.78 to 2.74). The per-protocol analysis revealed no significant effect
      either (adjusted HR 0.57, 95% CI 0.21 to 1.57), although the number of placements
      among the adherers was relatively low (9.4%). A subgroup effect was found for
      patients' age, with a significantly higher risk of institutionalization for
      'younger' patients in the intervention group compared with the usual care group
      (adjusted HR = 4.94, 95% CI 1.10 to 22.13). CONCLUSION: This family meetings
      intervention for primary caregivers of patients with dementia did not postpone
      patient institutionalization more than usual care. TRIAL REGISTRATION: CONTROLLED
      TRIALS.COM ISRCTN90163486.

PMID- 22876305
TI  - Antitumor activity of emodin against pancreatic cancer depends on its dual role:
      promotion of apoptosis and suppression of angiogenesis.
AB  - BACKGROUND: Emodin has been showed to induce apoptosis of pancreatic cancer cells
      and inhibit tumor growth in our previous studies. This study was designed to
      investigate whether emodin could inhibit the angiogenesis of pancreatic cancer
      tissues and its mechanism. METHODOLOGY/PRINCIPAL FINDING: In accordance with our
      previous study, emodin inhibited pancreatic cancer cell growth, induced
      apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner
      cells in vitro and in vivo by inhibiting the activity of NF-kappaB. Here, for the
      first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and
      in implanted pancreatic cancer tissues, decreased the expression of angiogenesis
      associated factors (NF-kappaB and its regulated factors VEGF, MMP-2, MMP-9, and
      eNOS), and reduced eNOS phosphorylation, as evidenced by both
      immunohistochemistry and western blot analysis of implanted tumors. In addition,
      we found that emodin had no effect on VEGFR expression in vivo.
      CONCLUSIONS/SIGNIFICANCE: Our results suggested that emodin has potential anti
      tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis
      and suppression of angiogenesis, probably through regulating the expression of NF
      kappaB and NF-kappaB-regulated angiogenesis-associated factors.

PMID- 22876306
TI  - Specialized motor-driven dusp1 expression in the song systems of multiple
      lineages of vocal learning birds.
AB  - Mechanisms for the evolution of convergent behavioral traits are largely unknown.
      Vocal learning is one such trait that evolved multiple times and is necessary in
      humans for the acquisition of spoken language. Among birds, vocal learning is
      evolved in songbirds, parrots, and hummingbirds. Each time similar forebrain song
      nuclei specialized for vocal learning and production have evolved. This finding
      led to the hypothesis that the behavioral and neuroanatomical convergences for
      vocal learning could be associated with molecular convergence. We previously
      found that the neural activity-induced gene dual specificity phosphatase 1
      (dusp1) was up-regulated in non-vocal circuits, specifically in sensory-input
      neurons of the thalamus and telencephalon; however, dusp1 was not up-regulated in
      higher order sensory neurons or motor circuits. Here we show that song motor
      nuclei are an exception to this pattern. The song nuclei of species from all
      known vocal learning avian lineages showed motor-driven up-regulation of dusp1
      expression induced by singing. There was no detectable motor-driven dusp1
      expression throughout the rest of the forebrain after non-vocal motor
      performance. This pattern contrasts with expression of the commonly studied
      activity-induced gene egr1, which shows motor-driven expression in song nuclei
      induced by singing, but also motor-driven expression in adjacent brain regions
      after non-vocal motor behaviors. In the vocal non-learning avian species, we
      found no detectable vocalizing-driven dusp1 expression in the forebrain. These
      findings suggest that independent evolutions of neural systems for vocal learning
      were accompanied by selection for specialized motor-driven expression of the
      dusp1 gene in those circuits. This specialized expression of dusp1 could
      potentially lead to differential regulation of dusp1-modulated molecular cascades
      in vocal learning circuits.

PMID- 22876307
TI  - Astrocyte inositol triphosphate receptor type 2 and cytosolic phospholipase A2
      alpha regulate arteriole responses in mouse neocortical brain slices.
AB  - Functional hyperemia of the cerebral vascular system matches regional blood flow
      to the metabolic demands of the brain. One current model of neurovascular control
      holds that glutamate released by neurons activates group I metabotropic glutamate
      receptors (mGluRs) on astrocytes, resulting in the production of diffusible
      messengers that act to regulate smooth muscle cells surrounding cerebral
      arterioles. The acute mouse brain slice is an experimental system in which
      changes in arteriole diameter can precisely measured with light microscopy.
      Stimulation of the brain slice triggers specific cellular responses that can be
      correlated to changes in arteriole diameter. Here we used inositol trisphosphate
      receptor type 2 (IP(3)R2) and cytosolic phospholipase A(2) alpha (cPLA(2)alpha)
      deficient mice to determine if astrocyte mGluR activation coupled to IP(3)R2
      mediated Ca(2+) release and subsequent cPLA(2)alpha activation is required for
      arteriole regulation. We measured changes in astrocyte cytosolic free Ca(2+) and
      arteriole diameters in response to mGluR agonist or electrical field stimulation
      in acute neocortical mouse brain slices maintained in 95% or 20% O(2). Astrocyte
      Ca(2+) and arteriole responses to mGluR activation were absent in IP(3)R2(-/-)
      slices. Astrocyte Ca(2+) responses to mGluR activation were unchanged by deletion
      of cPLA(2)alpha but arteriole responses to either mGluR agonist or electrical
      stimulation were ablated. The valence of changes in arteriole diameter
      (dilation/constriction) was dependent upon both stimulus and O(2) concentration.
      Neuron-derived NO and activation of the group I mGluRs are required for responses
      to electrical stimulation. These findings indicate that an
      mGluR/IP(3)R2/cPLA(2)alpha signaling cascade in astrocytes is required to
      transduce neuronal glutamate release into arteriole responses.

PMID- 22876308
TI  - Nras overexpression results in granulocytosis, T-cell expansion and early
      lethality in mice.
AB  - NRAS is a proto-oncogene involved in numerous myeloid malignancies. Here, we
      report on a mouse line bearing a single retroviral long terminal repeat inserted
      into Nras. This genetic modification resulted in an increased level of wild type
      Nras mRNA giving the possibility of studying the function and activation of wild
      type NRAS. Flow cytometry was used to show a variable but significant increase of
      immature myeloid cells in spleen and thymus, and of T-cells in the spleen. At an
      age of one week, homozygous mice began to retard compared to their wild type and
      heterozygous littermates. Two weeks after birth, animals started to progressively
      lose weight and die before weaning. Heterozygous mice showed a moderate increase
      of T-cells and granulocytes but survived to adulthood and were fertile. In
      homozygous and heterozygous mice Gfi1 and Gcsf mRNA levels were upregulated,
      possibly explaining the increment in immature myeloid cells detected in these
      mice. The short latency period indicates that Nras overexpression alone is
      sufficient to cause dose-dependent granulocytosis and T-cell expansion.

PMID- 22876309
TI  - Coagulation changes during presyncope and recovery.
AB  - Orthostatic stress activates the coagulation system. The extent of coagulation
      activation with full orthostatic load leading to presyncope is unknown. We
      examined in 7 healthy males whether presyncope, using a combination of head up
      tilt (HUT) and lower body negative pressure (LBNP), leads to coagulation changes
      as well as in the return to baseline during recovery. Coagulation responses
      (whole blood thrombelastometry, whole blood platelet aggregation, endogenous
      thrombin potential, markers of endothelial activation and thrombin generation),
      blood cell counts and plasma mass density (for volume changes) were measured
      before, during, and 20 min after the orthostatic stress. Maximum orthostatic load
      led to a 25% plasma volume loss. Blood cell counts, prothrombin levels, thrombin
      peak, endogenous thrombin potential, and tissue factor pathway inhibitor levels
      increased during the protocol, commensurable with hemoconcentration. The markers
      of endothelial activation (tissue factor, tissue plasminogen activator), and
      thrombin generation (F1+2, prothrombin fragments 1 and 2, and TAT, thrombin
      antithrombin complex) increased to an extent far beyond the hemoconcentration
      effect. During recovery, the markers of endothelial activation returned to
      initial supine values, but F1+2 and TAT remained elevated, suggestive of
      increased coagulability. Our findings of increased coagulability at 20 min of
      recovery from presyncope may have greater clinical significance than short-term
      procoagulant changes observed during standing. While our experiments were
      conducted in healthy subjects, the observed hypercoagulability during graded
      orthostatic challenge, at presyncope and in recovery may be an important risk
      factor particularly for patients already at high risk for thromboembolic events
      (e.g. those with coronary heart disease, atherosclerosis or hypertensives).

PMID- 22876310
TI  - HIV-1 subtype F1 epidemiological networks among Italian heterosexual males are
      associated with introduction events from South America.
AB  - About 40% of the Italian HIV-1 epidemic due to non-B variants is sustained by F1
      clade, which circulates at high prevalence in South America and Eastern Europe.
      Aim of this study was to define clade F1 origin, population dynamics and
      epidemiological networks through phylogenetic approaches. We analyzed pol
      sequences of 343 patients carrying F1 subtype stored in the ARCA database from
      1998 to 2009. Citizenship of patients was as follows: 72.6% Italians, 9.3% South
      Americans and 7.3% Rumanians. Heterosexuals, Homo-bisexuals, Intravenous Drug
      Users accounted for 58.1%, 24.0% and 8.8% of patients, respectively. Phylogenetic
      analysis indicated that 70% of sequences clustered in 27 transmission networks.
      Two distinct groups were identified; the first clade, encompassing 56 sequences,
      included all Rumanian patients. The second group involved the remaining clusters
      and included 10 South American Homo-bisexuals in 9 distinct clusters.
      Heterosexual modality of infection was significantly associated with the
      probability to be detected in transmission networks. Heterosexuals were prevalent
      either among Italians (67.2%) or Rumanians (50%); by contrast, Homo-bisexuals
      accounted for 71.4% of South Americans. Among patients with resistant strains the
      proportion of clustering sequences was 57.1%, involving 14 clusters (51.8%).
      Resistance in clusters tended to be higher in South Americans (28.6%) compared to
      Italian (17.7%) and Rumanian patients (14.3%). A striking proportion of
      epidemiological networks could be identified in heterosexuals carrying F1 subtype
      residing in Italy. Italian Heterosexual males predominated within epidemiological
      clusters while foreign patients were mainly Heterosexual Rumanians, both males
      and females, and South American Homo-bisexuals. Tree topology suggested that F1
      variant from South America gave rise to the Italian F1 epidemic through multiple
      introduction events. The contact tracing also revealed an unexpected burden of
      resistance in epidemiological clusters underlying the need of public
      interventions to limit the spread of non-B subtypes and transmitted drug
      resistance.

PMID- 22876311
TI  - Coalescent method in conjunction with niche modeling reveals cryptic diversity
      among centipedes in the Western Ghats of South India.
AB  - BACKGROUND: There has been growing interest in integrative taxonomy that uses
      data from multiple disciplines for species delimitation. Typically, in such
      studies, monophyly is taken as a proxy for taxonomic distinctiveness and these
      units are treated as potential species. However, monophyly could arise due to
      stochastic processes. Thus here, we have employed a recently developed tool based
      on coalescent approach to ascertain the taxonomic distinctiveness of various
      monophyletic units. Subsequently, the species status of these taxonomic units was
      further tested using corroborative evidence from morphology and ecology. This
      inter-disciplinary approach was implemented on endemic centipedes of the genus
      Digitipes (Attems 1930) from the Western Ghats (WG) biodiversity hotspot of
      India. The species of the genus Digitipes are morphologically conserved, despite
      their ancient late Cretaceous origin. PRINCIPAL FINDINGS: Our coalescent analysis
      based on mitochondrial dataset indicated the presence of nine putative species.
      The integrative approach, which includes nuclear, morphology, and climate
      datasets supported distinctiveness of eight putative species, of which three
      represent described species and five were new species. Among the five new
      species, three were morphologically cryptic species, emphasizing the
      effectiveness of this approach in discovering cryptic diversity in less explored
      areas of the tropics like the WG. In addition, species pairs showed variable
      divergence along the molecular, morphological and climate axes. CONCLUSIONS: A
      multidisciplinary approach illustrated here is successful in discovering cryptic
      diversity with an indication that the current estimates of invertebrate species
      richness for the WG might have been underestimated. Additionally, the importance
      of measuring multiple secondary properties of species while defining species
      boundaries was highlighted given variable divergence of each species pair across
      the disciplines.

PMID- 22876312
TI  - Attributable causes of esophageal cancer incidence and mortality in China.
AB  - BACKGROUND: To estimate the contribution of tobacco smoking, alcohol drinking,
      low vegetable intake and low fruit intake to esophageal cancer mortality and
      incidence in China. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the proportion
      of esophageal cancer attributable to four known modifiable risk factors
      [population attributable fraction (PAF)]. Exposure data was taken from meta
      analyses and large-scale national surveys of representative samples of the
      Chinese population. Data on relative risks were also from meta-analyses and large
      scale prospective studies. Esophageal cancer mortality and incidence came from
      the 3(rd) national death cause survey and population-based cancer registries in
      China. We estimated that 87,065 esophageal cancer deaths (men 67,686; women:
      19,379) and 108,206 cases (men: 83,968, women: 24,238) were attributable to
      tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake in
      China in 2005. About 17.9% of esophageal cancer deaths among men and 1.9% among
      women were attributable to tobacco smoking. About 15.2% of esophageal cancer
      deaths in men and 1.3% in women were caused by alcohol drinking. Low vegetable
      intake was responsible for 4.3% esophageal cancer deaths in men and 4.1% in
      women. The fraction of esophageal cancer deaths attributable to low fruit intake
      was 27.1% in men and 28.0% in women. Overall, 46% of esophageal cancers (51% in
      men and 33% in women) were attributable to these four modifiable risk factors.
      CONCLUSIONS/SIGNIFICANCE: Tobacco smoking, alcohol drinking, low vegetable intake
      and low fruit intake were responsible for 46% of esophageal cancer mortality and
      incidence in China in 2005. These findings provide useful data for developing
      guidelines for esophageal cancer prevention and control in China.

PMID- 22876313
TI  - Acute doxorubicin insult in the mouse ovary is cell- and follicle-type dependent.
AB  - Primary ovarian insufficiency (POI) is one of the many unintended consequences of
      chemotherapy faced by the growing number of female cancer survivors. While
      ovarian repercussions of chemotherapy have long been recognized, the acute insult
      phase and primary sites of damage are not well-studied, hampering efforts to
      design effective intervention therapies to protect the ovary. Utilizing
      doxorubicin (DXR) as a model chemotherapy agent, we defined the acute timeline
      for drug accumulation, induced DNA damage, and subsequent cellular and follicular
      demise in the mouse ovary. DXR accumulated first in the core ovarian stroma
      cells, then redistributed outwards into the cortex and follicles in a time
      dependent manner, without further increase in total ovarian drug levels after
      four hours post-injection. Consistent with early drug accumulation and intimate
      interactions with the blood supply, stroma cell-enriched populations exhibited an
      earlier DNA damage response (measurable at 2 hours) than granulosa cells
      (measurable at 4 hours), as quantified by the comet assay. Granulosa cell
      enriched populations were more sensitive however, responding with greater levels
      of DNA damage. The oocyte DNA damage response was delayed, and not measurable
      above background until 10-12 hours post-DXR injection. By 8 hours post-DXR
      injection and prior to the oocyte DNA damage response, the number of primary,
      secondary, and antral follicles exhibiting TUNEL (terminal deoxynucleotidyl
      transferase dUTP nick end labeling)-positive granulosa cells plateaued,
      indicating late-stage apoptosis and suggesting damage to the oocytes is
      subsequent to somatic cell failure. Primordial follicles accumulate significant
      DXR by 4 hours post-injection, but do not exhibit TUNEL-positive granulosa cells
      until 48 hours post-injection, indicating delayed demise. Taken together, the
      data suggest effective intervention therapies designed to protect the ovary from
      chemotherapy accumulation and induced insult in the ovary must act almost
      immediately to prevent acute insult as significant damage was seen in stroma
      cells within the first two hours.

PMID- 22876314
TI  - Silencing relaxin-3 in nucleus incertus of adult rodents: a viral vector-based
      approach to investigate neuropeptide function.
AB  - Relaxin-3, the most recently identified member of the relaxin peptide family, is
      produced by GABAergic projection neurons in the nucleus incertus (NI), in the
      pontine periventricular gray. Previous studies suggest relaxin-3 is a modulator
      of stress responses, metabolism, arousal and behavioural activation. Knockout
      mice and peptide infusions in vivo have significantly contributed to
      understanding the function of this conserved neuropeptide. Yet, a definitive role
      remains elusive due to discrepancies between models and a propensity to
      investigate pharmacological effects over endogenous function. To investigate the
      endogenous function of relaxin-3, we generated a recombinant adeno-associated
      viral (rAAV) vector expressing microRNA against relaxin-3 and validated its use
      to knock down relaxin-3 in adult rats. Bilateral stereotaxic infusion of rAAV1/2
      EmGFP miR499 into the NI resulted in significant reductions in relaxin-3
      expression as demonstrated by ablation of relaxin-3-like immunoreactivity at 3, 6
      and 9 weeks and by qRT-PCR at 12 weeks. Neuronal health was unaffected as
      transduced neurons in all groups retained expression of NeuN and stained for
      Nissl bodies. Importantly, qRT-PCR confirmed that relaxin-3 receptor expression
      levels were not altered to compensate for reduced relaxin-3. Behavioural
      experiments confirmed no detrimental effects on general health or well-being and
      therefore several behavioural modalities previously associated with relaxin-3
      function were investigated. The validation of this viral vector-based model
      provides a valuable alternative to existing in vivo approaches and promotes a
      shift towards more physiologically relevant investigations of endogenous
      neuropeptide function.

PMID- 22876316
TI  - Searching for sharp drops in the incidence of pandemic A/H1N1 influenza by single
      year of age.
AB  - BACKGROUND: During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality
      sparing was observed among the elderly population; it was hypothesized that this
      age group benefited from immunity to pH1N1 due to cross-reactive antibodies
      generated from prior infection with antigenically similar influenza viruses.
      Evidence from serologic studies and genetic similarities between pH1N1 and
      historical influenza viruses suggest that the incidence of pH1N1 cases should
      drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957,
      namely those at least 52-53 years old in 2009, but the precise range of ages
      affected has not been delineated. METHODS AND FINDINGS: To test for any age
      associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed
      pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of
      age, sex (when available), and hospitalization status. Using single year of age
      population denominators, we generated smoothed curves of the weighted risk ratio
      of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined
      as a significantly negative second derivative. Analyses stratified by
      hospitalization status and sex were used to test alternative explanations for
      observed discontinuities. We found that the risk of laboratory-confirmed
      infection with pH1N1 declines with age, but that there was a statistically
      significant leveling off or increase in risk from about 45 to 50 years of age,
      after which a sharp drop in risk occurs until the late fifties. This trend was
      more pronounced in hospitalized cases and in women and was independent of the
      choice in smoothing parameters. The age range at which the decline in risk
      accelerates corresponds to the cohort born between 1951-1959 (hospitalized) and
      1953-1960 (not hospitalized). CONCLUSIONS: The reduced incidence of pH1N1 disease
      in older individuals shows a detailed age-specific pattern consistent with
      protection conferred by exposure to influenza A/H1N1 viruses circulating before
      1957.

PMID- 22876317
TI  - The importance of GLUT3 for de novo lipogenesis in hypoxia-induced lipid loading
      of human macrophages.
AB  - Atherosclerotic lesions are characterized by lipid-loaded macrophages (foam
      cells) and hypoxic regions. Although it is well established that foam cells are
      produced by uptake of cholesterol from oxidized LDL, we previously showed that
      hypoxia also promotes foam cell formation even in the absence of exogenous
      lipids. The hypoxia-induced lipid accumulation results from increased
      triglyceride biosynthesis but the exact mechanism is unknown. Our aim was to
      investigate the importance of glucose in promoting hypoxia-induced de novo lipid
      synthesis in human macrophages. In the absence of exogenous lipids, extracellular
      glucose promoted the accumulation of Oil Red O-stained lipid droplets in human
      monocyte-derived macrophages in a concentration-dependent manner. Lipid droplet
      accumulation was higher in macrophages exposed to hypoxia at all assessed
      concentrations of glucose. Importantly, triglyceride synthesis from glucose was
      increased in hypoxic macrophages. GLUT3 was highly expressed in macrophage-rich
      and hypoxic regions of human carotid atherosclerotic plaques and in macrophages
      isolated from these plaques. In human monocyte-derived macrophages, hypoxia
      increased expression of both GLUT3 mRNA and protein, and knockdown of GLUT3 with
      siRNA significantly reduced both glucose uptake and lipid droplet accumulation.
      In conclusion, we have shown that hypoxia-induced increases in glucose uptake
      through GLUT3 are important for lipid synthesis in macrophages, and may
      contribute to foam cell formation in hypoxic regions of atherosclerotic lesions.

PMID- 22876318
TI  - Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key
      endocannabinoid and fatty acid receptors.
AB  - Enteroendocrine cells have a critical role in regulation of appetite and energy
      balance. I-cells are a subtype of enteroendocrine cells localized in duodenum
      that release cholecystokinin in response to ingested fat and amino-acids. Despite
      their potentially pivotal role in nutrient sensing and feeding behaviour, native
      I-cells have previously been difficult to isolate and study. Here we describe a
      robust protocol for the isolation and characterization of native duodenal I-cells
      and additionally, using semi-quantitative RT-PCR we determined that mouse
      duodenal I-cells contain mRNA transcripts encoding key fatty acid and
      endocannabinoid receptors including the long chain fatty acid receptors
      GPR40/FFAR1, GPR120/O3FAR1; short chain fatty acid receptors GPR41/FFAR3 and
      GPR43/FFAR2; the oleoylethanolamide receptor GPR119 and the classic
      endocannabinoid receptor CB1. These data suggest that I-cells sense a wide range
      of gut lumen nutrients and also have the capacity to respond to signals of fatty
      acid derivatives or endocannabinoid peptides.

PMID- 22876319
TI  - Ancient DNA analyses reveal contrasting phylogeographic patterns amongst kiwi
      (Apteryx spp.) and a recently extinct lineage of spotted kiwi.
AB  - The little spotted kiwi (Apteryx owenii) is a flightless ratite formerly found
      throughout New Zealand but now greatly reduced in distribution. Previous
      phylogeographic studies of the related brown kiwi (A. mantelli, A. rowi and A.
      australis), with which little spotted kiwi was once sympatric, revealed extremely
      high levels of genetic structuring, with mitochondrial DNA haplotypes often
      restricted to populations. We surveyed genetic variation throughout the present
      and pre-human range of little spotted kiwi by obtaining mitochondrial DNA
      sequences from contemporary and ancient samples. Little spotted kiwi and great
      spotted kiwi (A. haastii) formed a monophyletic clade sister to brown kiwi.
      Ancient samples of little spotted kiwi from the northern North Island, where it
      is now extinct, formed a lineage that was distinct from remaining little spotted
      kiwi and great spotted kiwi lineages, potentially indicating unrecognized
      taxonomic diversity. Overall, little spotted kiwi exhibited much lower levels of
      genetic diversity and structuring than brown kiwi, particularly through the South
      Island. Our results also indicate that little spotted kiwi (or at least hybrids
      involving this species) survived on the South Island mainland until more recently
      than previously thought.

PMID- 22876315
TI  - Rates of decline in Alzheimer disease decrease with age.
AB  - Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the
      effects of age on rates of clinical decline and brain atrophy in AD have been
      largely unexplored. Here, we examined longitudinal rates of change as a function
      of baseline age for measures of clinical decline and structural MRI-based
      regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and
      cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The
      effect of age was modeled using mixed effects linear regression. There was
      pronounced reduction in rates of clinical decline and atrophy with age for AD and
      MCI individuals, whereas HCs showed increased rates of clinical decline and
      atrophy with age. This resulted in convergence in rates of change for HCs and
      patients with advancing age for several measures. Baseline cerebrospinal fluid
      densities of AD-relevant proteins, Abeta(1-42), tau, and phospho-tau(181p)
      (ptau), showed a similar pattern of convergence with advanced age across cohorts,
      particularly for ptau. In contrast, baseline clinical measures did not differ by
      age, indicating uniformity of clinical severity at baseline. These results imply
      that the phenotypic expression of AD is relatively mild in individuals older than
      approximately 85 years, and this may affect the ability to distinguish AD from
      normal aging in the very old. Our findings show that inclusion of older
      individuals in clinical trials will substantially reduce the power to detect
      disease-modifying therapeutic effects, leading to dramatic increases in required
      clinical trial sample sizes with age of study sample.

PMID- 22876320
TI  - Identification and analysis of cation channel homologues in human pathogenic
      fungi.
AB  - Fungi are major causes of human, animal and plant disease. Human fungal
      infections can be fatal, but there are limited options for therapy, and
      resistance to commonly used anti-fungal drugs is widespread. The genomes of many
      fungi have recently been sequenced, allowing identification of proteins that may
      become targets for novel therapies. We examined the genomes of human fungal
      pathogens for genes encoding homologues of cation channels, which are prominent
      drug targets. Many of the fungal genomes examined contain genes encoding
      homologues of potassium (K(+)), calcium (Ca(2+)) and transient receptor potential
      (Trp) channels, but not sodium (Na(+)) channels or ligand-gated channels. Some
      fungal genomes contain multiple genes encoding homologues of K(+) and Trp channel
      subunits, and genes encoding novel homologues of voltage-gated K(v) channel
      subunits are found in Cryptococcus spp. Only a single gene encoding a homologue
      of a plasma membrane Ca(2+) channel was identified in the genome of each
      pathogenic fungus examined. These homologues are similar to the Cch1 Ca(2+)
      channel of Saccharomyces cerevisiae. The genomes of Aspergillus spp. and
      Cryptococcus spp., but not those of S. cerevisiae or the other pathogenic fungi
      examined, also encode homologues of the mitochondrial Ca(2+) uniporter (MCU). In
      contrast to humans, which express many K(+), Ca(2+) and Trp channels, the genomes
      of pathogenic fungi encode only very small numbers of K(+), Ca(2+) and Trp
      channel homologues. Furthermore, the sequences of fungal K(+), Ca(2+), Trp and
      MCU channels differ from those of human channels in regions that suggest
      differences in regulation and susceptibility to drugs.

PMID- 22876321
TI  - Impact of toxigenic Clostridium difficile colonization and infection among
      hospitalized adults at a district hospital in southern Taiwan.
AB  - BACKGROUND: The impact of toxigenic Clostridium difficile colonization (tCDC) in
      hospitalized patients is not clear. AIM: To study the significance of tCDC in
      hospitalized patients. METHODS: A prospective study in the medical wards of a
      regional hospital was performed from January to June 2011. Fecal samples
      collected from patients at the time of admission were tested for tcdB by real
      time polymerase chain reaction (PCR) and cultured for C. difficile. The patients
      were followed up weekly or when they developed diarrhea during hospitalization.
      If C. difficile was isolated, tcdA and tcdB would be tested by multiplex PCR. The
      primary outcome was the development of C. difficile-associated diarrhea (CDAD).
      FINDINGS: Of 168 patients enrolled, females predominated (87, 51.8%), and the
      mean patient age was 75.4 years old. Approximately 70% of the patients were
      nursing home residents, and one third had a recent hospitalization within the
      prior three months. Twenty-eight (16.7%) patients had tCDC, including 16 (9.5%)
      patients with tCDC at the time of admission and 12 (7.2%) with tCDC during the
      follow-up period. With regard to the medications taken during hospitalization,
      the patients were more likely to have tCDC if they had received more than one
      class of antibiotics than if they had received monotherapy (odds ratio [OR] 6.67,
      95% confidence interval [CI] 1.41-31.56, P = 0.01), particularly if they received
      a glycopeptide in combination with a cephalosporin or penicillin or a
      cephalosporin and a carbapenem. More patients with tCDC developed CDAD than those
      without tCDC (17.9%, 5/28 vs. 1.4%, 2/140, P = 0.002). Overall 7 (4.2%) of the
      168 patients developed CDAD, and crude mortality rate of those with and without
      tCDC was similar (21.4%, 6/28 vs. 19.4%, 27/140, P = 0.79). CONCLUSION: Recent
      use of glycopeptides and beta-lactam antibiotics is associated with toxigenic C.
      difficile colonization, which is a risk factor for developing C. difficile
      associated diarrhea.

PMID- 22876323
TI  - Local tertiary structure probing of ribonucleoprotein particles by nuclease
      fusion proteins.
AB  - Analyses of the conformational dynamics of the numerous cellular
      ribonucleoprotein particles (RNP) significantly contribute to the understanding
      of their modes of action. Here, we tested whether ribonuclease fusion proteins
      incorporated into RNPs can be used as molecular probes to characterize the local
      RNA environment of these proteins. Fusion proteins of micrococcal nuclease
      (MNase) with ribosomal proteins were expressed in S. cerevisae to produce in vivo
      recombinant ribosomes which have a ribonuclease tethered to specific sites.
      Activation of the MNase activity by addition of calcium led to specific rRNA
      cleavage events in proximity to the ribosomal binding sites of the fusion
      proteins. The dimensions of the RNP environment which could be probed by this
      approach varied with the size of the linker sequence between MNase and the fused
      protein. Advantages and disadvantages of the use of MNase fusion proteins for
      local tertiary structure probing of RNPs as well as alternative applications for
      this type of approach in RNP research are discussed.

PMID- 22876322
TI  - Genetic variants in ER cofactor genes and endometrial cancer risk.
AB  - Given that the transcriptional regulatory activity of estrogen receptor (ER) is
      modulated by its biochemical cofactors, genetic variation within the ER cofactor
      genes may alter cellular response to estrogen exposure and consequently modify
      the risk for endometrial cancer. We genotyped 685 tagging SNPs within 60 ER
      cofactor genes in 564 endometrial cancer cases and 1,510 controls from Sweden,
      and tested their associations with the risk of endometrial cancer. We
      investigated the associations of individual SNPs by using a trend test as well as
      multiple SNPs within a gene or gene complex by using multi-variant association
      analysis. No significant association was observed for any individual SNPs or
      genes, but a marginal association of the cumulative genetic variation of the
      NCOA2 complex as a whole (NCOA2, CARM1, CREBBP, PRMT1 and EP300) with endometrial
      cancer risk was observed (P(adjusted) = 0.033). However, the association failed
      to be replicated in an independent European dataset of 1265 cases and 5190
      controls (P = 0.71). The results indicate that common genetic variants within ER
      cofactor genes are unlikely to play a significant role in endometrial cancer risk
      in European population.

PMID- 22876324
TI  - Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces
      cerevisiae.
AB  - As a key intracellular metabolite, acetyl-coenzyme A (acetyl-CoA) plays a major
      role in various metabolic pathways that link anabolism and catabolism. In the
      yeast Saccharomyces cerevisiae, acetyl-CoA involving metabolism is
      compartmentalized, and may vary with the nutrient supply of a cell. Membranes
      separating intracellular compartments are impermeable to acetyl-CoA and no direct
      transport between the compartments occurs. Thus, without carnitine supply the
      glyoxylate shunt is the sole possible route for transferring acetyl-CoA from the
      cytosol or the peroxisomes into the mitochondria. Here, we investigate the
      physiological profiling of different deletion mutants of ACS1, ACS2, CIT2 and
      MLS1 individually or in combination under alternative carbon sources, and study
      how various mutations alter carbon distribution. Based on our results a detailed
      model of carbon distribution about cytosolic and peroxisomal acetyl-CoA
      metabolism in yeast is suggested. This will be useful to further develop yeast as
      a cell factory for the biosynthesis of acetyl-CoA-derived products.

PMID- 22876325
TI  - Functional characterization of 8-oxoguanine DNA glycosylase of Trypanosoma cruzi.
AB  - The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair
      by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair
      with adenine, and the excision of this damaged base by Ogg1 enables the insertion
      of a guanine and prevents DNA mutation. In this report, we identified and
      characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1), the
      causative agent of Chagas disease. Like most living organisms, T. cruzi is
      susceptible to oxidative stress, hence DNA repair is essential for its survival
      and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG
      DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae
      strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of
      the yeast mutant ogg1(-/-) (CD138) to wild type levels. We also demonstrate that
      the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide
      (H(2)O(2)). Analysis of DNA lesions using quantitative PCR suggests that the
      increased susceptibility to H(2)O(2) of TcOGG1-overexpressor could be a
      consequence of uncoupled BER in abasic sites and/or strand breaks generated after
      TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER
      enzymes. This hypothesis is supported by the observation that TcOGG1
      overexpressors have reduced levels of 8-oxoG both in the nucleus and in the
      parasite mitochondrion. The localization of TcOgg1 was examined in parasite
      transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both
      organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1
      ortholog that participates in nuclear and mitochondrial BER.

PMID- 22876326
TI  - Isoform-specific dominant-negative effects associated with hERG1 G628S mutation
      in long QT syndrome.
AB  - BACKGROUND: Mutations in the human ether-a-go-go-related gene 1 (hERG1) cause
      type 2 long QT syndrome (LQT2). The hERG1 gene encodes a K(+) channel with
      properties similar to the rapidly activating delayed rectifying K(+) current in
      the heart. Several hERG1 isoforms with unique structural and functional
      properties have been identified. To date, the pathogenic mechanisms of LQT2
      mutations have been predominantly described in the context of the hERG1a isoform.
      In the present study, we investigated the functional consequences of the LQT2
      mutation G628S in the hERG1b and hERG1a(USO) isoforms. METHODS: A double-stable,
      mammalian expression system was developed to characterize isoform-specific
      dominant-negative effects of G628S-containing channels when co-expressed at
      equivalent levels with wild-type hERG1a. Western blot and co-immunoprecipitation
      studies were performed to study the trafficking and co-assembly of wild-type and
      mutant hERG1 isoforms. Patch-clamp electrophysiology was performed to
      characterize hERG1 channel function and the isoform-specific dominant-negative
      effects associated with the G628S mutation. CONCLUSIONS: The non-functional
      hERG1a-G628S and hERG1b-G628S channels co-assembled with wild-type hERG1a and
      dominantly suppressed hERG1 current. In contrast, G628S-induced dominant-negative
      effects were absent in the context of the hERG1a(USO) isoform. hERG1a(USO)-G628S
      channels did not appreciably associate with hERG1a and did not significantly
      suppress hERG1 current when co-expressed at equivalent ratios or at ratios that
      approximate those found in cardiac tissue. These results suggest that the
      dominant-negative effects of LQT2 mutations may primarily occur in the context of
      the hERG1a and hERG1b isoforms.

PMID- 22876327
TI  - In situ optical mapping of voltage and calcium in the heart.
AB  - Electroanatomic mapping the interrelation of intracardiac electrical activation
      with anatomic locations has become an important tool for clinical assessment of
      complex arrhythmias. Optical mapping of cardiac electrophysiology combines high
      spatiotemporal resolution of anatomy and physiological function with fast and
      simultaneous data acquisition. If applied to the clinical setting, this could
      improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia
      interventions. The aim of this study was to explore this utility in vivo using a
      rat model. To this aim, we present a single-camera imaging and multiple light
      emitting-diode illumination system that reduces economic and technical
      implementation hurdles to cardiac optical mapping. Combined with a red-shifted
      calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use
      in blood-perfused tissue, we demonstrate the feasibility of in vivo multi
      parametric imaging of the mammalian heart. Our approach combines recording of
      electrophysiologically-relevant parameters with observation of structural
      substrates and is adaptable, in principle, to trans-catheter percutaneous
      approaches.

PMID- 22876328
TI  - Differences in time until dispersal between cryptic species of a marine nematode
      species complex.
AB  - Co-occurrence of closely related species may be achieved in environments with
      fluctuating dynamics, where competitively inferior species can avoid competition
      through dispersal. Here we present an experiment in which we compared active
      dispersal abilities (time until first dispersal, number and gender of dispersive
      adults, and nematode densities at time of dispersal) in Litoditis marina, a
      common bacterivorous nematode species complex comprising four often co-occurring
      cryptic species, Pm I, II, III, and IV, as a function of salinity and food
      distribution. The experiment was conducted in microcosms consisting of an
      inoculation plate, connection tube, and dispersal plate. Results show species
      specific dispersal abilities with Pm I dispersing almost one week later than Pm
      III. The number of dispersive adults at time of first dispersal was species
      specific, with one dispersive female in Pm I and Pm III and a higher, gender
      balanced, number in Pm II and Pm IV. Food distribution affected dispersal: in
      absence of food in the inoculation plate, all species dispersed after ca four
      days. When food was available Pm I dispersed later, and at the same time and
      densities irrespective of food conditions in the dispersal plate (food vs no
      food), suggesting density-dependent dispersal. Pm III dispersed faster and at a
      lower population density. Salinity affected dispersal, with slower dispersal at
      higher salinity. These results suggest that active dispersal in Litoditis marina
      is common, density-dependent, and with species, gender- and environment-specific
      dispersal abilities. These differences can lead to differential responses under
      suboptimal conditions and may help to explain temporary coexistence at local
      scales.

PMID- 22876329
TI  - SpecNet: a spatial network algorithm that generates a wide range of specific
      structures.
AB  - Network measures are used to predict the behavior of different systems. To be
      able to investigate how various structures behave and interact we need a wide
      range of theoretical networks to explore. Both spatial and non-spatial methods
      exist for generating networks but they are limited in the ability of producing
      wide range of network structures. We extend an earlier version of a spatial
      spectral network algorithm to generate a large variety of networks across almost
      all the theoretical spectra of the following network measures: average clustering
      coefficient, degree assortativity, fragmentation index, and mean degree. We
      compare this extended spatial spectral network-generating algorithm with a non
      spatial algorithm regarding their ability to create networks with different
      structures and network measures. The spatial spectral network-generating
      algorithm can generate networks over a much broader scale than the non-spatial
      and other known network algorithms. To exemplify the ability to regenerate real
      networks, we regenerate networks with structures similar to two real Swedish
      swine transport networks. Results show that the spatial algorithm is an
      appropriate model with correlation coefficients at 0.99. This novel algorithm can
      even create negative assortativity and managed to achieve assortativity values
      that spans over almost the entire theoretical range.

PMID- 22876330
TI  - Hypoxia-induced alternative splicing in endothelial cells.
AB  - BACKGROUND: Adaptation to low oxygen by changing gene expression is vitally
      important for cell survival and tissue development. The sprouting of new blood
      vessels, initiated from endothelial cells, restores the oxygen supply of ischemic
      tissues. In contrast to the transcriptional response induced by hypoxia, which is
      mainly mediated by members of the HIF family, there are only few studies
      investigating alternative splicing events. Therefore, we performed an exon array
      for the genome-wide analysis of hypoxia-related changes of alternative splicing
      in endothelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Human umbilical vein
      endothelial cells (HUVECs) were incubated under hypoxic conditions (1% O(2)) for
      48 h. Genome-wide transcript and exon expression levels were assessed using the
      Affymetrix GeneChip Human Exon 1.0 ST Array. We found altered expression of 294
      genes after hypoxia treatment. Upregulated genes are highly enriched in glucose
      metabolism and angiogenesis related processes, whereas downregulated genes are
      mainly connected to cell cycle and DNA repair. Thus, gene expression patterns
      recapitulate known adaptations to low oxygen supply. Alternative splicing events,
      until now not related to hypoxia, are shown for nine genes: six which are
      implicated in angiogenesis-mediated cytoskeleton remodeling (cask, itsn1, larp6,
      sptan1, tpm1 and robo1); one, which is involved in the synthesis of membrane
      anchors (pign) and two universal regulators of gene expression (cugbp1 and max).
      CONCLUSIONS/SIGNIFICANCE: For the first time, this study investigates changes in
      splicing in the physiological response to hypoxia on a genome-wide scale. Nine
      alternative splicing events, until now not related to hypoxia, are reported,
      considerably expanding the information on splicing changes due to low oxygen
      supply. Therefore, this study provides further knowledge on hypoxia induced gene
      expression changes and presents new starting points to study the hypoxia
      adaptation of endothelial cells.

PMID- 22876331
TI  - Climate and weather impact timing of emergence of bats.
AB  - Interest in forecasting impacts of climate change have heightened attention in
      recent decades to how animals respond to variation in climate and weather
      patterns. One difficulty in determining animal response to climate variation is
      lack of long-term datasets that record animal behaviors over decadal scales. We
      used radar observations from the national NEXRAD network of Doppler weather
      radars to measure how group behavior in a colonially-roosting bat species
      responded to annual variation in climate and daily variation in weather over the
      past 11 years. Brazilian free-tailed bats (Tadarida brasiliensis) form dense
      aggregations in cave roosts in Texas. These bats emerge from caves daily to
      forage at high altitudes, which makes them detectable with Doppler weather
      radars. Timing of emergence in bats is often viewed as an adaptive trade-off
      between emerging early and risking predation or increased competition and
      emerging late which restricts foraging opportunities. We used timing of emergence
      from five maternity colonies of Brazilian free-tailed bats in south-central Texas
      during the peak lactation period (15 June-15 July) to determine whether emergence
      behavior was associated with summer drought conditions and daily temperatures.
      Bats emerged significantly earlier during years with extreme drought conditions
      than during moist years. Bats emerged later on days with high surface
      temperatures in both dry and moist years, but there was no relationship between
      surface temperatures and timing of emergence in summers with normal moisture
      levels. We conclude that emergence behavior is a flexible animal response to
      climate and weather conditions and may be a useful indicator for monitoring
      animal response to long-term shifts in climate.

PMID- 22876332
TI  - Gastrointestinal cancers and the cooperative groups-2011.
AB  - There have been extensive changes in the operation of the U.S. cooperative group
      structure over the past 5 to 10 years that have major implications for the
      functioning of the clinical trial system. They relate to the formation of disease
      specific steering committees and task forces, the findings and implementation of
      the Operational Efficiency Working Group (OEWG), and the overall restructuring of
      the cooperative groups themselves. I will discuss these topics separately. Many
      of the changes resulted from three reports issued by the Clinical Trials Working
      Group (http://ccct.cancer.gov/about/reports#clinical_trials), the Translational
      Research Working Group (http://ccct.cancer.gov/about/reports#clinical_trials),
      and the Institute of Medicine (http://www.iom.edu/Reports/2010/A-National-Cancer
      Clinical-Trials-System-for-the-21st-Century-Reinvigorating-the-NCI
      Cooperative.aspx).

PMID- 22876333
TI  - S-1 plus intravenous and intraperitoneal Paclitaxel for gastric cancer with
      peritoneal metastasis.
AB  - Peritoneal metastasis is the most frequent and life-threatening type of
      metastasis in patients with advanced gastric cancer. Despite recent advances in
      chemotherapeutic agents, any treatment, if administered only via the intravenous
      (IV) route, cannot satisfactorily control peritoneal metastasis in gastric
      cancer. Although intraperitoneal (IP) chemotherapy has been proposed as a
      treatment option, the clinical efficacy of IP chemotherapy for peritoneal lesions
      has not been examined in gastrointestinal cancer. One hundred patients with
      gastric cancer received combination chemotherapy of S-1 plus IV (50 mg/m(2)) and
      IP (20 mg/m(2)) paclitaxel (PTX) via a subcutaneously implanted peritoneal access
      port. S-1 was administered at 80 mg/m(2) per day for 14 consecutive days,
      followed by 7 days' rest. Radical gastrectomy was performed in a salvage setting
      when macroscopic curative resection was made feasible by the downstaging achieved
      by the combined chemotherapy. The median survival time (MST) of the patient
      sample was 23.6 months, with a 1-year survival of 80%. Combination chemotherapy
      of S-1 plus IV and IP PTX is well tolerated and very effective in patients with
      gastric cancer and peritoneal metastasis. Systemic chemotherapy combined with
      repeated IP administration of paclitaxel is a promising strategy for peritoneal
      carcinomatosis in gastrointestinal cancer.

PMID- 22876334
TI  - What's New in Transarterial Therapies for Hepatocellular Carcinoma?
AB  - Transarterial therapies play an important role in the treatment of hepatocellular
      carcinoma, both in a palliative setting and as an adjunct to surgery. These
      therapies exploit the dual blood supply of the liver to selectively target tumors
      via the hepatic artery, while sparing nontumorous liver. Currently available
      therapies include transarterial embolization; chemoembolization, with or without
      drug-eluting beads; and radioembolization. Transarterial techniques are also
      being used in the development of novel therapies. This article provides an
      outline of the technical and clinical applications of intraarterial therapies in
      the treatment of HCC and highlights pertinent future directions.

PMID- 22876336
TI  - Advances in CT Imaging of GI Malignancies.
AB  - There have been multiple advances in multidetector CT over the past decades which
      have directly improved the quality of oncologic imaging. Not only has the most
      recent generation of CT scanners allowed markedly improved spatial and temporal
      resolutions, but modern imaging protocols have been refined and are now
      specifically tailored to the patient's known malignancy. Moreover, the last few
      years have also seen the widespread use of 3-D imaging (including volume
      rendering and maximum intensity projection imaging), which has also markedly
      improved the quality of CT diagnosis. This article discusses the state-of-the-art
      advances in the imaging of pancreatic, hepatic, and small bowel malignancies,
      each of which illustrates the strengths of modern MDCT in oncologic diagnosis and
      staging.

PMID- 22876337
TI  - Near-infrared laser-assisted indocyanine green imaging for optimizing the design
      of the anterolateral thigh flap.
AB  - OBJECTIVE: The anterolateral thigh flap is a versatile flap that can be used in a
      free or pedicled fashion. Because of the large amount of potential soft tissue,
      low donor site morbidity, and long pedicle lengths, many researchers consider it
      to be the perfect free flap. However, dissection of this and other perforator
      flaps can become an arduous experience with learning curves to overcome. Near
      infrared laser angiography using indocyanine green provides a useful adjunctive
      tool to more predictably assess direct perforator perfusion zones. Laser-assisted
      angiography with SPY-Q analysis gives live localization of the flap's dominant
      perforator perfusion zones while quantifying the relative tissue perfusion for
      immediate skin paddle design. METHODS: Fifteen patients with head and neck cancer
      defects were reconstructed with a free anterolateral thigh flap using laser
      assisted near-infrared indocyanine green perforator mapping. The mid-point of a
      line between the anterior superior iliac spine and the patella was determined and
      the laser was centered over this. Indocyanine green (12.5 mg) was injected
      intravenously and fluorescence patterns were recorded. Optimal perforators were
      chosen using real-time imaging and SPY-Q analysis software. The anterolateral
      thigh skin paddle was centered over perforators based on best relative perfusion
      values. The hand-held Doppler was not used to identify perforators. All flaps
      were elevated in standard fashion. Patient demographics, defect characteristics,
      reconstructive techniques, and clinical outcomes were assessed. RESULTS: All 15
      free flaps were raised with the assistance of laser-assisted angiography.
      Cutaneous Doppler did not aid in the design of the skin paddle. There was only 1
      flap loss due to venous congestion. All donor defects were closed primarily
      without the need for a skin graft. CONCLUSIONS: Laser-assisted indocyanine green
      angiography using SPY-Q analysis software provides robust, intraoperative,
      objective data to optimize anterolateral thigh skin paddle design while
      potentially minimizing patient morbidity. Future studies will be needed to
      further evaluate the use of this new technology.

PMID- 22876338
TI  - Symmetrical peripheral gangrene.

PMID- 22876339
TI  - Communication activity in a social network: relation between long-term
      correlations and inter-event clustering.
AB  - Human communication in social networks is dominated by emergent statistical laws
      such as non-trivial correlations and temporal clustering. Recently, we found long
      term correlations in the user's activity in social communities. Here, we extend
      this work to study the collective behavior of the whole community with the goal
      of understanding the origin of clustering and long-term persistence. At the
      individual level, we find that the correlations in activity are a byproduct of
      the clustering expressed in the power-law distribution of inter-event times of
      single users, i.e. short periods of many events are separated by long periods of
      no events. On the contrary, the activity of the whole community presents long
      term correlations that are a true emergent property of the system, i.e. they are
      not related to the distribution of inter-event times. This result suggests the
      existence of collective behavior, possibly arising from nontrivial communication
      patterns through the embedding social network.

PMID- 22876340
TI  - Linear magnetoresistance in n-type silicon due to doping density fluctuations.
AB  - We report the observation of a large linear magnetoresistance in the ohmic regime
      in commonplace commercial n-type silicon wafer with a P dopant density of (1.4+/
      0.1) *10(15) cm(-3), and report measurements of it in the temperature range 30
      200 K. It arises from the deformation of current paths, which causes a part of
      the Hall field to be detected at the voltage probes. In short, wide samples we
      found linear magnetoresistance as large as 4707% in an 8 tesla field at 35 K.
      Sample geometry effects like these are commonplace in commercial Hall sensors.
      However, we found that the effect persisted in long, thin samples where the
      macroscopic current flow should be uniform between the voltage probes: we
      observed a magnetoresistance of 445% under the same conditions as above. We
      interpret this result as arising due to spatial fluctuations in the donor
      density, in the spirit of the Herring model.

PMID- 22876342
TI  - Generalized cell morphological parameters based on interferometric phase
      microscopy and their application to cell life cycle characterization.
AB  - We present analysis tools which are formulated using wide-field interferometric
      phase microscopy measurements, and show their ability to uniquely quantify the
      life cycle of live cancer cells. These parameters are based directly on the
      optical path delay profile of the sample and do not necessitate decoupling the
      refractive index and the thickness in the cell interferometric phase profile, and
      thus can be calculated using a single-frame acquisition. To demonstrate the use
      of these parameters, we have constructed a wide-field interferometric phase
      microscopy setup and closely traced the full lifecycle of HeLa cancer cells.
      These initial results show the potential of the parameters to distinguish between
      the different phases of the cell lifecycle, as well others biological phenomena.

PMID- 22876341
TI  - Mechanisms for redox actions of nicotine and glutathione in cell culture,
      relevant to periodontitis.
AB  - The oxidative effect of nicotine was investigated using androgen biomarkers of
      redox status and wound healing in fibroblasts; using the antioxidant glutathione
      for confirmation of responses. Cultures of human gingival (HGF) and periosteal
      fibroblasts (HPF) were incubated with substrates 14C-testosterone/14C-4
      androstenedione in the presence or absence of serial concentrations of nicotine
      (N(100-500)), glutathione (G(1-5)) and their combinations, in medium. At 24 h the
      medium was solvent extracted for metabolites, separated by TLC and quantified
      using radioisotope scanning. Nicotine caused significant inhibition in yields of
      the physiologically active metabolite 5alpha-dihydrotestosterone (DHT) in HGF and
      HPF, overcome to varying degrees by the anti-oxidant glutathione (n = 6; p<0.01,
      one way ANOVA); this is suggestive of moderation of an oxidative mechanism
      induced by nicotine. Down-regulation of 5alpha-reductase activity by nicotine
      resulting in reduced yields of DHT was overcome by glutathione. Overcoming
      oxidative stress in a redox environment is applicable to treatment outcome.

PMID- 22876343
TI  - Motion correction of in vivo three-dimensional optical coherence tomography of
      human skin using a fiducial marker.
AB  - This paper presents a novel method based on a fiducial marker for correction of
      motion artifacts in 3D, in vivo, optical coherence tomography (OCT) scans of
      human skin and skin scars. The efficacy of this method was compared against a
      standard cross-correlation intensity-based registration method. With a fiducial
      marker adhered to the skin, OCT scans were acquired using two imaging protocols:
      direct imaging from air into tissue; and imaging through ultrasound gel into
      tissue, which minimized the refractive index mismatch at the tissue surface. The
      registration methods were assessed with data from both imaging protocols and
      showed reduced distortion of skin features due to motion. The fiducial-based
      method was found to be more accurate and robust, with an average RMS error below
      20 um and success rate above 90%. In contrast, the intensity-based method had an
      average RMS error ranging from 36 to 45 um, and a success rate from 50% to 86%.
      The intensity-based algorithm was found to be particularly confounded by
      corrugations in the skin. By contrast, tissue features did not affect the
      fiducial-based method, as the motion correction was based on delineation of the
      flat fiducial marker. The average computation time for the fiducial-based
      algorithm was approximately 21 times less than for the intensity-based algorithm.

PMID- 22876344
TI  - Spectral discrimination between normal and leukemic human sera using delayed
      luminescence.
AB  - In this work, photoinduced delayed luminescence (DL) was used to distinguish
      serum samples of patients with acute lymphoblastic leukemia from those of healthy
      volunteers. DL decay kinetics of human serum samples was measured using a
      homebuilt ultraweak luminescence detection system. It was found a significant
      difference in the weight distribution of the decay rate between normal and
      leukemic serum samples. A comparison of the DL kinetics parameters including the
      initial intensity, the peak decay rate, and the peak weight value was used in
      making discrimination between normal and leukemic human sera. Results in this
      work contribute to the development of a novel optical method for the early
      diagnosis of leukemia.

PMID- 22876345
TI  - Light scattering from edematous human corneal grafts' microstructure:
      experimental study and electromagnetic modelization.
AB  - Along with the lens, the cornea is the only transparent tissue in the human body.
      However, the development of an edema involves structural disturbances increasing
      light scattering and leading to the opacification of the cornea. Several
      mechanisms of transparency loss have been studied in the literature, but the
      whole phenomenon is complex and the part played by each scatterer is still
      unclear. We propose here to study human corneal grafts combining microscopic OCT
      imagery with far-field measurement of the scattered light in the reflected half
      space. We introduce afterwards numerical calculations based on electromagnetic
      equations solved with first order approximation to link the observed microscopic
      scale structural modifications with the intensity level of the scattered light,
      and to try and quantify the relationship between them.

PMID- 22876346
TI  - Limitations to adaptive optics image quality in rodent eyes.
AB  - Adaptive optics (AO) retinal image quality of rodent eyes is inferior to that of
      human eyes, despite the promise of greater numerical aperture. This paradox
      challenges several assumptions commonly made in AO imaging, assumptions which may
      be invalidated by the very high power and dioptric thickness of the rodent
      retina. We used optical modeling to compare the performance of rat and human eyes
      under conditions that tested the validity of these assumptions. Results showed
      that AO image quality in the human eye is robust to positioning errors of the AO
      corrector and to differences in imaging depth and wavelength compared to the
      wavefront beacon. In contrast, image quality in the rat eye declines sharply with
      each of these manipulations, especially when imaging off-axis. However, some
      latitude does exist to offset these manipulations against each other to produce
      good image quality.

PMID- 22876347
TI  - Auto-fluorescence lifetime and light reflectance spectroscopy for breast cancer
      diagnosis: potential tools for intraoperative margin detection.
AB  - This study investigates the use of two spectroscopic techniques, auto
      fluorescence lifetime measurement (AFLM) and light reflectance spectroscopy
      (LRS), for detecting invasive ductal carcinoma (IDC) in human ex vivo breast
      specimens. AFLM used excitation at 447 nm with multiple emission wavelengths
      (532, 562, 632, and 644 nm), at which auto-fluorescence lifetimes and their
      weight factors were analyzed using a double exponent model. LRS measured
      reflectance spectra in the range of 500-840 nm and analyzed the spectral slopes
      empirically at several distinct spectral regions. Our preliminary results based
      on 93 measured locations (i.e., 34 IDC, 31 benign fibrous, 28 adipose) from 6
      specimens show significant differences in 5 AFLM-derived parameters and 9 LRS
      based spectral slopes between benign and malignant breast samples. Multinomial
      logistic regression with a 10-fold cross validation approach was implemented with
      selected features to classify IDC from benign fibrous and adipose tissues for the
      two techniques independently as well as for the combined dual-modality approach.
      The accuracy for classifying IDC was found to be 96.4 +/- 0.8%, 92.3 +/- 0.8% and
      96 +/- 1.3% for LRS, AFLM, and dual-modality, respectively.

PMID- 22876348
TI  - Structured oblique illumination microscopy for enhanced resolution imaging of non
      fluorescent, coherently scattering samples.
AB  - Many biological structures of interest are beyond the diffraction limit of
      conventional microscopes and their visualization requires application of super
      resolution techniques. Such techniques have found remarkable success in
      surpassing the diffraction limit to achieve sub-diffraction limited resolution;
      however, they are predominantly limited to fluorescent samples. Here, we
      introduce a non-fluorescent analogue to structured illumination microscopy,
      termed structured oblique illumination microscopy (SOIM), where we use
      simultaneous oblique illuminations of the sample to multiplex high spatial
      frequency content into the frequency support of the system. We introduce a
      theoretical framework describing how to demodulate this multiplexed information
      to reconstruct an image with a spatial-frequency support exceeding that of the
      system's classical diffraction limit. This approach allows enhanced-resolution
      imaging of non-fluorescent samples. Experimental confirmation of the approach is
      obtained in a reflection test target with moderate numerical aperture.

PMID- 22876349
TI  - Dual-channel spectrally encoded endoscopic probe.
AB  - High quality imaging through sub-millimeter endoscopic probes provides clinicians
      with valuable diagnostics capabilities in hard to reach locations within the
      body. Spectrally encoded endoscopy (SEE) has been shown promising for such task;
      however, challenging probe fabrication and high speckle noise had prevented its
      testing in in vivo studies. Here we demonstrate a novel miniature SEE probe which
      incorporates some of the recent progress in spectrally encoded technology into a
      compact and robust endoscopic system. A high-quality miniature diffraction
      grating was fabricated using automated femtosecond laser cutting from a large
      bulk grating. Using one spectrally encoded channel for imaging and a separate
      channel for incoherent illumination, the new system has large depth of field,
      negligible back reflections and well controlled speckle noise which depends on
      the core diameter of the illumination fiber. Moreover, by using a larger imaging
      channel, higher groove density grating, shorter wavelength and broader spectrum,
      the new endoscopic system now allow significant improvements in almost all
      imaging parameter compared to previous systems, through an ultra-miniature
      endoscopic probe.

PMID- 22876350
TI  - Strain estimation in phase-sensitive optical coherence elastography.
AB  - We present a theoretical framework for strain estimation in optical coherence
      elastography (OCE), based on a statistical analysis of displacement measurements
      obtained from a mechanically loaded sample. We define strain sensitivity, signal
      to-noise ratio and dynamic range, and derive estimates of strain using three
      methods: finite difference, ordinary least squares and weighted least squares,
      the latter implemented for the first time in OCE. We compare theoretical
      predictions with experimental results and demonstrate a ~12 dB improvement in
      strain sensitivity using weighted least squares compared to finite difference
      strain estimation and a ~4 dB improvement over ordinary least squares strain
      estimation. We present strain images (i.e., elastograms) of tissue-mimicking
      phantoms and excised porcine airway, demonstrating in each case clear contrast
      based on the sample's elasticity.

PMID- 22876351
TI  - Dual-mode laparoscopic fluorescence image-guided surgery using a single camera.
AB  - Iatrogenic nerve damage is a leading cause of morbidity associated with many
      common surgical procedures. Complications arising from these injuries may result
      in loss of function and/or sensation, muscle atrophy, and chronic neuropathy.
      Fluorescence image-guided surgery offers a potential solution for avoiding
      intraoperative nerve damage by highlighting nerves that are otherwise difficult
      to visualize. In this work we present the development of a single camera, dual
      mode laparoscope that provides near simultaneous display of white-light and
      fluorescence images of nerves. The capability of the instrumentation is
      demonstrated through imaging several types of in situ rat nerves via a nerve
      specific contrast agent. Full color white light and high brightness fluorescence
      images and video of nerves as small as 100 um in diameter are presented.

PMID- 22876352
TI  - Trapping and rotating microparticles and bacteria with moire-based optical
      propelling beams.
AB  - We propose and demonstrate trapping and rotation of microparticles and biological
      samples with a moire-based rotating optical tweezers. We show that polystyrene
      beads, as well as Escherichia coli cells, can be rotated with ease, while the
      speed and direction of rotation are fully controllable by a computer, obviating
      mechanical movement or phase-sensitive interference. Furthermore, we demonstrate
      experimentally the generation of white-light propelling beams and arrays, and
      discuss the possibility of optical tweezing and particle micro-manipulation based
      on incoherent white-light rotating patterns.

PMID- 22876353
TI  - 3D resolved mapping of optical aberrations in thick tissues.
AB  - We demonstrate a simple method for mapping optical aberrations with 3D resolution
      within thick samples. The method relies on the local measurement of the variation
      in image quality with externally applied aberrations. We discuss the accuracy of
      the method as a function of the signal strength and of the aberration amplitude
      and we derive the achievable resolution for the resulting measurements. We then
      report on measured 3D aberration maps in human skin biopsies and mouse brain
      slices. From these data, we analyse the consequences of tissue structure and
      refractive index distribution on aberrations and imaging depth in normal and
      cleared tissue samples. The aberration maps allow the estimation of the typical
      aplanetism region size over which aberrations can be uniformly corrected. This
      method and data pave the way towards efficient correction strategies for tissue
      imaging applications.

PMID- 22876354
TI  - Multispectral nanoparticle contrast agents for true-color spectroscopic optical
      coherence tomography.
AB  - We have recently developed a novel dual window scheme for processing
      spectroscopic OCT images to provide spatially resolved true color imaging of
      chromophores in scattering samples. Here we apply this method to measure the
      extinction spectra of plasmonic nanoparticles at various concentrations for
      potential in vivo applications. We experimentally demonstrate sub-nanomolar
      sensitivity in the measurement of nanoparticle concentrations, and show that
      colorimetric imaging with multiple species of nanoparticles produces enhanced
      contrast for spectroscopic OCT in both tissue phantom and cell studies.

PMID- 22876355
TI  - Nondestructive volumetric imaging of tissue microstructure with benchtop x-ray
      phase-contrast tomography and critical point drying.
AB  - The in vitro investigation of many optically opaque biological microstructures
      requires 3D analysis at high resolution over a large field of view. We
      demonstrate a new nondestructive volumetric imaging technique that eliminates the
      structural and computational limitations of conventional 2D optical microscopy by
      combining x-ray phase-contrast tomography with critical point drying sample
      preparation. We experimentally demonstrate the enhancement of small features
      afforded by phase-contrast imaging and show the contrast improvement afforded by
      the drying of a hydrated specimen. We further demonstrate the biological
      application of this technique by imaging the microstructure of the accommodative
      apparatus in a primate eye using a benchtop phase-contrast tomography system.

PMID- 22876356
TI  - Measurement of the oxidation state of mitochondrial cytochrome c from the
      neocortex of the mammalian brain.
AB  - Diffuse optical remission spectra from the mammalian neocortex at visible
      wavelengths contain spectral features originating from the mitochondria. A new
      algorithm is presented, based on analytically relating the first differential of
      the attenuation spectrum to the first differential of the chromophore spectra,
      that can separate and calculate the oxidation state of cytochrome c as well as
      the absolute concentration and saturation of hemoglobin. The algorithm is
      validated in phantoms and then tested on the neocortex of the rat during an
      anoxic challenge. Implementation of the algorithm will provide detailed
      information of mitochondrial oxygenation and mitochondrial function in
      physiological studies of the mammalian brain.

PMID- 22876357
TI  - Flexible transbronchial optical frequency domain imaging smart needle for biopsy
      guidance.
AB  - Transbronchial needle aspiration (TBNA) is a procedure routinely performed to
      diagnose peripheral pulmonary lesions. However, TBNA is associated with a low
      diagnostic yield due to inappropriate needle placement. We have developed a
      flexible transbronchial optical frequency domain imaging (TB-OFDI) catheter that
      functions as a "smart needle" to confirm the needle placement within the target
      lesion prior to biopsy. The TB-OFDI smart needle consists of a flexible and
      removable OFDI catheter (430 um dia.) that operates within a standard 21-gauge
      TBNA needle. The OFDI imaging core is based on an angle polished ball lens design
      with a working distance of 160 um from the catheter sheath and a spot size of 25
      um. To demonstrate the potential of the TB-OFDI smart needle for transbronchial
      imaging, an inflated excised swine lung was imaged through a standard
      bronchoscope. Cross-sectional and longitudinal OFDI results reveal the detailed
      network of alveoli in the lung parenchyma suggesting that the TB-OFDI smart
      needle may be a useful tool for guiding biopsy acquisition to increase the
      diagnostic yield.

PMID- 22876358
TI  - Focal switching of photochromic fluorescent proteins enables multiphoton
      microscopy with superior image contrast.
AB  - Probing biological structures and functions deep inside live organisms with light
      is highly desirable. Among the current optical imaging modalities, multiphoton
      fluorescence microscopy exhibits the best contrast for imaging scattering samples
      by employing a spatially confined nonlinear excitation. However, as the incident
      laser power drops exponentially with imaging depth into the sample due to the
      scattering loss, the out-of-focus background eventually overwhelms the in-focus
      signal, which defines a fundamental imaging-depth limit. Herein we significantly
      improve the image contrast for deep scattering samples by harnessing reversibly
      switchable fluorescent proteins (RSFPs) which can be cycled between bright and
      dark states upon light illumination. Two distinct techniques, multiphoton
      deactivation and imaging (MPDI) and multiphoton activation and imaging (MPAI),
      are demonstrated on tissue phantoms labeled with Dronpa protein. Such a focal
      switch approach can generate pseudo background-free images. Conceptually
      different from wave-based approaches that try to reduce light scattering in
      turbid samples, our work represents a molecule-based strategy that focused on
      imaging probes.

PMID- 22876359
TI  - MUTYH-associated polyposis (MAP), the syndrome implicating base excision repair
      in inherited predisposition to colorectal tumors.
AB  - In 2002, Al-Tassan and co-workers described for the first time a recessive form
      of inherited polyposis associated with germline mutations of MUTYH, a gene
      encoding a base excision repair (BER) protein that counteracts the DNA damage
      induced by the oxidative stress. MUTYH-associated polyposis (MAP) is now a well
      defined cancer susceptibility syndrome, showing peculiar molecular features that
      characterize disease progression. However, some aspects of MAP, including
      diagnostic criteria, genotype-phenotype correlations, pathogenicity of variants,
      as well as relationships between BER and other DNA repair pathways, are still
      poorly understood. A deeper knowledge of the MUTYH expression pattern is likely
      to refine our understanding of the protein role and, finally, to improve
      guidances for identifying and handling MAP patients.

PMID- 22876360
TI  - Targeting myelogenous leukemia stem cells: role of the circulation.
AB  - Unlike stem cells from solid tumors, the stem cells which initiate myelogenous
      leukemias arise in marrow, an organ with a unique circulation which allows ready
      access of leukemia cells, including leukemia stem cells (LSCs), to the
      vasculature. This poses unique problems in the targeting of LSCs since these
      cells are found circulating in the majority of leukemia cases at diagnosis and
      are usually not detectable during remission states. Because most cases of
      leukemia relapse, it is suggested that LSCs remain quiescent in the marrow until
      they eventually proliferate and circulate again. This indicates that effective
      targeting of LSCs must occur not only in peripheral circulation but in the micro
      circulation of the marrow. Targeting such interactions may overcome cell adhesion
      mediated treatment resistance, other multi-drug resistance mechanisms, and
      opportunities for clonal evolution in the marrow environment. Targeting selectins
      and integrins, signal transduction mediators, and chemokine/cytokine networks in
      the marrow micro-circulation may aid in abrogating leukemia-initiating stem cells
      which contribute to disease relapse. LSCs possess surface antigen profiles and
      signal transduction activation profiles which may allow differential targeting as
      compared with normal hematopoietic stem cells.

PMID- 22876362
TI  - Relapsing polychondritis on PET/CT.
AB  - Relapsing polychondritis is a rare multisystemic disease, which is characterized
      by recurrent inflammation of the cartilaginous structures. We report a case of a
      37-year-old man with progressive respiratory distress. Chest Computed tomography
      (CT) demonstrated increased attenuation and smooth thickening of airway walls.
      Positron emission tomography/CT scan identified the multisystemic cartilaginous
      abnormalities that were recognized by an increased fluorine-18 deoxyglucose
      uptake on nasal cartilages, laryngeal cartilages, tracheobronchial tree, and rib
      cartilages. Positron emission tomography/CT is a useful tool to diagnose
      relapsing polychondritis, as the condition shows multisystemic cartilaginous
      abnormalities that can be identified by an increased fluorine-18 deoxyglucose
      uptake.

PMID- 22876361
TI  - Endoplasmic reticulum involvement in yeast cell death.
AB  - Yeast cells undergo programed cell death (PCD) with characteristic markers
      associated with apoptosis in mammalian cells including chromatin breakage,
      nuclear fragmentation, reactive oxygen species generation, and metacaspase
      activation. Though significant research has focused on mitochondrial involvement
      in this phenomenon, more recent work with both Saccharomyces cerevisiae and
      Schizosaccharomyces pombe has also implicated the endoplasmic reticulum (ER) in
      yeast PCD. This minireview provides an overview of ER stress-associated cell
      death (ER-SAD) in yeast. It begins with a description of ER structure and
      function in yeast before moving to a discussion of ER-SAD in both mammalian and
      yeast cells. Three examples of yeast cell death associated with the ER will be
      highlighted here including inositol starvation, lipid toxicity, and the
      inhibition of N-glycosylation. It closes by suggesting ways to further examine
      the involvement of the ER in yeast cell death.

PMID- 22876363
TI  - ANAC 2012 Public Policy Agenda.

PMID- 22876364
TI  - An inflammatory proposal for hepatocarcinogenesis.

PMID- 22876365
TI  - When activated oncogene meets immunity: a fight to prevent liver tumor
      initiation.

PMID- 22876366
TI  - Activated hepatic stellate cells: negative regulators of hepatocyte proliferation
      in liver diseases.

PMID- 22876367
TI  - The promise and pitfalls of population health.

PMID- 22876368
TI  - Bad forms.

PMID- 22876369
TI  - Joining EHR forces.

PMID- 22876392
TI  - Ditzels.

PMID- 22876393
TI  - Comparison of oral status in an adult population 35-75 year of age in the county
      of Dalarna, Sweden in 1983 and 2008.
AB  - The aim was to study the prevalence and distribution of number of teeth, number
      of intact and decayed teeth and prevalence and distribution of removable dentures
      and periodontal disease over 25 years 1983-2008. Two cross-sectional studies
      (EpiWux) were performed in the County of Dalarna, Sweden in 1983 and 2008. In the
      1983 study a random sample of 1012 individuals were invited to participate in
      this epidemiological and clinical study and 1440 individuals in 2008. A total
      number of 1695 individuals, stratified into geographical areas (rural and urban
      areas), in the age groups 35, 50, 65 and 75 answered a questionnaire and were
      also clinically and radiographically examined.The number of edentulous
      individuals decreased from 15% in 1983 to 3% in 2008. Number of teeth increased
      from 22.7 in 1983 to 24.2 in 2008 and decayed surfaces per tooth showed a three
      time reduction over this period of time. As a consequence of better oral status
      the prevalence of complete removable dentures in both jaws decreased from 15% in
      1983 to 2% in 2008. Individuals with moderate periodontitis decreased from 45% in
      1983 to 16% in 2008. CONCLUSION: Covering a period of 25 years the present study
      can report dramatic improvements in all aspects of dental status that were
      investigated.This is encouraging for dental care professionals, but will not
      necessarily lead to less demand for dental care in the future as the population
      is aging with a substantial increase in number of teeth.

PMID- 22876394
TI  - A dental phobia treatment within the Swedish National Health Insurance.
AB  - Severe dental fear/phobia (DF) is a problem for both dental care providers and
      for patients who often suffer from impaired oral health and from social and
      emotional distress.The aim of this paper was to present the Swedish model for DF
      treatment within the National Health Insurance System, and to describe the dental
      phobia treatment and its outcome at The Dental Fear Research and Treatment Clinic
      (DFRTC) in Gothenburg. A literature review was made of relevant policy documents
      on dental phobia treatment from the National Health Insurance System and for
      Vastra Gotaland region on published outcome studies from DFRTC. The treatment
      manual of DFRTC was also used. In Sweden, adult patients with severe DF are able
      to undergo behavioral treatment within the National Health Insurance System if
      the patient and caregivers fulfil defined criteria that must be approved for each
      individual case. At DFRTC dental phobia behavioral treatment is given by
      psychologists and dentists in an integrated model. The goal is to refer patients
      for general dental care outside the DFRTC after completing treatment. The DF
      treatment at DFRTC has shown positive effects on dental fear, attendance and
      acceptance of dental treatment for 80% of patients. Follow-up after 2 and 10
      years confirmed these results and showed improved oral health. In addition,
      positive psychosomatic and psychosocial side-effects were reported, and benefits
      also for society were evident in terms of reduced sick-leave. In conlusion, in
      Sweden a model has been developed within the National Health Insurance System
      helping individuals with DF. Behavioral treatment conducted at DFRTC has proven
      successful in helping patients cope with dental care, leading to regular
      attendance and better oral health.

PMID- 22876395
TI  - Dentists' views on fearful patients. Problems and promises.
AB  - A large number of patients treated in the general dental health service in
      Western countries report dental fear to some degree. Dentists' views of treating
      these fearful patients are not well described in the literature.Therefore, the
      aims of the study were to explore dentists' attitudes towards, experience of, and
      feelings about treating fearful patients. The sample consisted of 1293 members of
      the Association of Public Health Dentists in Sweden who were asked to respond to
      a web survey concerning dental fear. The response rate was 69% (n = 889).The
      majority of the responding dentists stated that dental fear is a problem in
      routine dental care,treating patients with dental fear is a positive challenge
      and they felt they were making a contribution.They also reported that treating
      patients with dental fear is associated with hard work, poor revenues, and little
      appreciation by employers. Female dentists reported a greater proportion of
      patients with dental fear and greater self-efficacy regarding the treatment of
      these patients, compared with their male colleagues. Dentists trained in other EU
      countries reported stress more often and less perceived contribution when
      treating fearful patients, compared with colleagues trained in Sweden.
      CONCLUSION: Dentists' views of treating fearful patients are mainly positive;
      however, it is problematic that dentists feel stress and that dentists who treat
      many fearful patients feel their employers do not appreciate their efforts.

PMID- 22876396
TI  - Rinsing with alcohol-free or alcohol-based chlorhexidine solutions after
      periodontal surgery. A double-blind, randomized, cross-over, pilot study.
AB  - The aim of this randomized, double-blind, cross-over pilot study was to evaluate
      the effect on plaque formation and patient experience of rinsing after
      periodontal surgery using chlorhexidine solution with or without alcohol. Twenty
      patients refrained from tooth brushing after surgery and used two mouth
      rinses.Ten patients used alcohol-based (AB) 0.1% and another ten used alcohol
      free (AF) 0.12% chlorhexidine (CHX). Sutures were removed after 2 weeks and teeth
      were cleaned; thereafter, the two groups shifted solution. Plaque at operated
      teeth was recorded at 2 and 4 weeks (Quigley-Hein Index). Patient experience was
      assessed with a visual analogue scale (0-10). Mean (SD) plaque indices at 2 and 4
      weeks were 1.0 (0.8) and 1.1 (1.0) for AB CHX and 1.1 (0.7) and 0.8 (0.7) for AF
      CHX, respectively (no significant differences between solutions). At 2 weeks,
      between-group differences in taste experience of the solutions differed non
      significantly: 6.1 (2.8) for AB and 6.0 (2.3) for AF. At 4 weeks, values were 4.6
      (2.5) for AB and 6.9 (3.3) for AF-patients tended to prefer AF (p = 0.050). Taste
      change over the study period was equal for both groups: -37 (3.3) for AB and 3.4
      (2.3) for AF at 2 weeks and slightly higher at 4 weeks 4.9 (2.8) and 4.5 (2.5)
      for AB and AF, respectively. Smarting was low in both groups: 2.2 (3.2) and 1.3
      (2.2) for AB and 1.0 (1.5) and 1.9 (2.0) for AF at 2 and 4 weeks, respectively.
      To conclude, alcohol-free and alcohol-based chlorhexidine showed the same plaque
      inhibitory effect in periodontal patients after periodontal surgery. Both rinses
      were well tolerated by the patients.

PMID- 22876397
TI  - Homocystinuria and oral health. A report of 14 cases.
AB  - The aim of this study was to explore the oral health in Swedish individuals with
      the diagnosis of homozygote cystathionine beta synthase-deficient homocystinuria
      (HC), a rare disorder of amino acid metabolism affecting connective tissue, in
      which the phenotypic abnormalities include dislocation of the optic lens,
      skeletal abnormalities, thromboembolic events, and sometimes mental retardation.
      Further aims were to evaluate the oral findings against previous oral
      observations in a medical case report, such as high narrow palate, mandibular
      prognathia, crowding and early eruption of teeth. Every hospital in Sweden was
      contacted, with the inquiry of patients with diagnosis of HC,which resulted in 14
      individuals participating in oral clinical examination. The oral findings
      evaluated against previous medical case reports showed to be partly in accordance
      with previous observations. Dental health showed to be compromised in a majority
      of cases. Together with the fact that methionine restriction (low-protein diet)
      is involved in the treatment of the condition and might result in a diet high in
      sugars, this points out the role of regular dental checkups and preventive oral
      care for individuals suffering from HC. In addition, short dental roots were a
      finding not previously reported in the literature. All the studied cases had
      central maxillary incisors with short roots, when compared to reference values
      used.

PMID- 22876398
TI  - Going for gold this summer.

PMID- 22876399
TI  - Government denies that more people are waiting too long.

PMID- 22876400
TI  - Changes to emergency care provision may lead to creation of 'super' units.

PMID- 22876402
TI  - A new strategy for patients with dementia.
AB  - There are 800,000 people with dementia in the UK, of whom about 82,000 live in
      Scotland. The general population is ageing, and because the risk of developing
      dementia increases with age, the number of people with dementia in Scotland is
      expected to double over the next 25 years (Alzheimer Scotland 2011). A sharp
      increase in the number of people with dementia who present to emergency
      departments (EDs) and acute care settings. Up to one in four of all general
      hospital beds in the UK are occupied by people aged over 65 years who have
      dementia (Alzheimer's Society 2009), yet their specific needs are often poorly
      understood by healthcare staff (Alzheimer's Society 2009, Mental Welfare
      Commission 2010). This article describes the development of an online resource
      for ED staff in Scotland, and of the associated infrastructure, to improve the
      care experience for people with dementia, their families and carers.

PMID- 22876403
TI  - Massive blood transfusion for trauma patients.
AB  - Transfusion of large amounts of blood products is a complex and changing
      practice. British and American military experience of the process in Afghanistan
      and Iraq, and the findings of the international CRASH 2 study (Shakur et al
      2010), have led to changes in practice (Moor et al 2009). The procedure has
      evolved into a targeted therapy involving a selection of blood products and
      drugs. This article explores the practice of massive transfusion adopted by the
      British military in Afghanistan, including the drugs used, and describes the
      training given to staff in a controlled environment.

PMID- 22876404
TI  - Emergency management of hyperemesis gravidarum.
AB  - Most pregnant women experience morning sickness during the first 20 weeks of
      pregnancy. Often, the symptoms are mild, but recurring, nausea and vomiting; but
      the condition can also lead to dehydration, weight loss, electrolyte imbalance
      and blood volume depletion, and many women with more severe forms of the
      condition present to emergency departments. This article describes the presenting
      symptoms, causes of hyperemesis gravidarum, the associated clinical signs and
      complications, and the most common treatments offered.

PMID- 22876405
TI  - Role of advanced paediatric nurse practitioners.
AB  - Children's attendance at emergency departments (EDs) is increasing every year,
      yet many children present with minor, self-limiting illnesses that could be
      managed at home. In light of Williams et al (2009) suggestion that healthcare
      professionals should improve the care available to patients at point of contact
      rather than try to change their health-seeking behaviours, this article describes
      how Tameside and Glossop Primary Care Trust has developed an advanced paediatric
      nurse practitioner (APNP) service in the ED to improve the care of children, and
      to reduce the number of admissions. The APNPs treat children in the ED then
      divert them to more appropriate services where support is given to the families
      to care for their children at home. The role contributes to meeting ED clinical
      quality indicators, frees up medical staff to deal with more seriously ill
      patients, and makes financial savings for the trust.

PMID- 22876406
TI  - Managing risk in your dental practice.

PMID- 22876407
TI  - Practice housekeeping: things to do even if you are not selling your practice.

PMID- 22876408
TI  - Fracastoro and the prognosis of applicants with HIV.
AB  - OBJECTIVES: Discuss the relevance of the study "Trends in mortality of insurance
      applicants with HIV infection" by highlighting the key elements for underwriting
      HIV-positive life insurance applicants. METHODS: Discussion on the basis of a
      comparison of HIV with syphilis, as presented by Giralmo Fracastoro; and by
      comparing HIV prevalence in applicants and the background population. RESULTS: As
      with syphilis, adherence to therapy is a key element; different from syphilis is
      the importance of co-morbidity. The prevalence in life insurance applicants
      remains stab, while the prevalence in the population increases. CONCLUSIONS: The
      self selection of applicants with co-morbidity is the major reason for the
      continuing high relative mortality of HIV-positive applicants.

PMID- 22876409
TI  - Death master file--RIP.

PMID- 22876410
TI  - Trends in mortality of insurance applicants with HIV infection.
AB  - OBJECTIVE: Provide a brief review of HIV history and determine the relative
      mortality of life insurance applicants who are HIV positive and how that has
      changed over time with advances in treatment. METHOD: By use of the Social
      Security Death Master File and multivariate analysis, mortality of those HIV
      positive relative to those HIV negative was determined for life insurance
      applicants from 1991 to 2009. RESULTS: Relative mortality varied by type of
      testing (blood, urine or oral fluid) and by age, ranging from 320% at the oldest
      ages to over 1300% at the youngest ages for applicants with blood testing.
      Surprisingly, there was little change in relative risk among HIV-positive
      applicants over this period. CONCLUSION: Relative risk for life insurance
      applicants who are HIV positive remains high despite advances in therapy.

PMID- 22876411
TI  - Urine protein/creatinine ratio as a mortality risk predictor in non-diabetics
      with normal renal function.
AB  - OBJECTIVE: Determine the relative mortality in apparently healthy adults with
      various levels of urinary protein measured by urine protein/creatinine (p/c)
      ratio. METHOD: By use of the Social Security Death Master File, mortality in 2010
      was determined for 7.5 million life insurance applicants age 20 to 89 providing
      urine samples between 1992 and 2006. Relative mortality by Cox regression for
      bands of p/c ratios was determined using age and sex as covariates and with an
      age split at 60 after excluding those with hematuria (> 3 red cells/hpf),
      diabetes, evidence of blood sugar elevation, or eGFR < 60 mL/min. RESULTS: After
      the exclusions noted above, relative mortality increased to 160% beginning at a
      p/c ratio of 0.11 mg/mg and rose steadily above that value regardless of sex and
      age. Most of this risk was not explained by a history of hypertension or elevated
      systolic blood pressure. Albumin testing identified roughly a third of urine
      samples with elevated p/c ratios as not containing albumin; those cases appeared
      to be associated with much lower risk as long as the p/c ratio was < or = 1.0
      mg/mg. CONCLUSION: Low levels of proteinuria identified as urine
      protein/creatinine ratios of 0.11 mg/mg or higher (much lower than the usual
      lower cut-off value of 0.21) are associated with substantial excess mortality
      risk, even after excluding diabetics and those with reduced kidney function or
      hematuria.

PMID- 22876412
TI  - White matter hyperintensities: age appropriate or risk indicator?
AB  - White matter hypertensity (WMH) is a term frequently seen in the MRI reports of
      insurance applicants. Its significance is often uncertain. There are different
      patterns and extent of WMH of variable clinical significance can be identified.
      Pathological correlates are varied with most pointing toward WMH as a reflection
      of small vessel ischemic burden. The predominant clinical associations are with
      stroke, cognitive impairment, dementia, general disability and death. This review
      examines the relationship of white matter hyperintensities to client morbidity,
      disability and mortality from an insurance medicine perspective.

PMID- 22876413
TI  - Health insurer policies toward risk-stratified colorectal cancer screening: a
      survey of health plan medical directors.
AB  - OBJECTIVES: We sought to determine whether health insurance coverage of
      colorectal cancer (CRC) screening varied based on risk. BACKGROUND: Population
      wide screening guidelines for cancer often incorporate risk information, with
      modified screening recommendations for those at higher risk due to family history
      or other factors. METHODS: In a nationwide Internet- and mail-based survey of
      health insurance plan medical directors, respondents were asked about their
      organization's policies towards coverage of CRC screening for persons at average
      and higher risk of CRC. Additional questions asked about whether the insurer had
      a definition of increased risk, and coverage of genetic testing for familial CRC
      syndromes. RESULTS: Survey invitations were sent to 1158 medical directors; 133
      (11%) completed the survey. All plans covered screening for average and high-risk
      persons. The onset of screening was earlier and intervals were more frequent for
      higher risk compared to average risk persons, with most respondents stating
      coverage was determined by "physician discretion." While 75% had a definition of
      high risk, only 55% covered genetic testing. CONCLUSIONS: Most insurers offer
      enhanced coverage of CRC screening, most commonly following the discretion of the
      physician. Whether this coverage results in earlier, more frequent, or more
      complete screening of higher risk persons remains uncertain.

PMID- 22876414
TI  - Sinus bradycardia: normal phenomenon or risk factor? Evaluation based on recent
      evidence.
AB  - Although sinus bradycardia is a common abnormality seen in medical reports, the
      proper evaluation of sinus bradycardia is poorly understood by physicians. Recent
      data from heart rate epidemiologic and cohort studies has emerged regarding the
      risk stratification of sinus bradycardia, which may help insurers better
      underwrite this abnormality. In this review, an operational age-related heart
      rate reference based on recent advances is provided along with a suggested
      approach to the risk stratification and assessment of prognosis for inappropriate
      sinus bradycardia.

PMID- 22876415
TI  - A copper for your thoughts.

PMID- 22876416
TI  - "Flat line" in a limb lead.
AB  - A life insurance applicant's electrocardiogram shows a flat line in one of the
      standard leads and new Q waves in the inferior leads. The clinical and risk
      assessment implications are reviewed.

PMID- 22876417
TI  - Abnormal head CT imaging in Iraq.

PMID- 22876418
TI  - Breaking up the NHS is devastating for its staff.

PMID- 22876419
TI  - Lansley imposes pension reforms despite calls for more consultation.

PMID- 22876420
TI  - Chief nurse defends PFI debts of trust taken over by administrators.

PMID- 22876421
TI  - Staff transferring to local councils fear threat to terms and conditions.

PMID- 22876422
TI  - NICE recommends a four-hour response to suspected blood clots.

PMID- 22876423
TI  - Regulator urged to cut number of fitness to practise referrals.

PMID- 22876424
TI  - A place to unwind.
AB  - The final article in our leadership series reveals how a learning disability
      forensic trust made spirituality a core element of a leadership programme for
      ward managers.

PMID- 22876425
TI  - In a tight spin.
AB  - A major report on the impact of the financial crisis on nurses and nursing in
      Europe has highlighted job losses and deep salary cuts in the worst-affected
      areas. Nurses in northern and Scandinavian countries are generally faring better
      than nurses in the south and east.

PMID- 22876426
TI  - 'These people left their handprints on my heart'.

PMID- 22876427
TI  - Management of hemiplegic shoulder pain following stroke.
AB  - Shoulder pain is a common problem following stroke. Patients may present with
      varying degrees of paralysis (hemiplegia), which commonly affects the arm. As a
      consequence, the stability of the shoulder may be compromised with subsequent
      risk of damage to soft tissue structures. Patients with more severe paralysis of
      the arm are increasingly likely to develop shoulder pain. The underlying causes
      of shoulder pain, and the sources of this pain, have been the subject of debate
      and research for many years. There is recent evidence to suggest that damage to
      soft tissues can occur during post-stroke care in hospital. An evidence-based,
      multidisciplinary approach should be used to prevent damage to the shoulder and
      enable management of any complications that arise.

PMID- 22876428
TI  - Introduction to the life sciences series and homeostasis.
AB  - The aim of this series is to examine the life sciences in the context of clinical
      nursing practice and explore the basic structure and function of the human body.
      The series will examine different aspects of anatomy and physiology, assisting
      the reader to make essential links between theory and practice. This article
      introduces the series, describes some basic anatomical terms and outlines the
      concept of homeostasis and feedback systems.

PMID- 22876429
TI  - Mentoring students in medicines management.
AB  - Medicines management is an important part of the nurse's role. It covers elements
      such as cost-effectiveness, patient advice, infection control, optimising
      benefits from medicines, emerging technological developments, and drug
      administration and storage. The aim of this article is to enable mentors to
      support pre-registration nursing students to develop specific proficiencies in
      medicines management. The focus will be on applying pharmacological knowledge to
      practice, communicating patient information and avoiding medicine administration
      errors.

PMID- 22876430
TI  - Sexual health.

PMID- 22876431
TI  - Caring about a better outcome.

PMID- 22876432
TI  - Keep compassion alive.

PMID- 22876433
TI  - Development and evaluation of a traditional Chinese medicine syndrome
      questionnaire for measuring sub-optimal health status in China.
AB  - OBJECTIVE: Sub-optimal health status (SHS), in which a person's mind and body
      exists in a low-quality state of being between disease and health, has become a
      public health problem that cannot be ignored in China. SHS measurement presents a
      challenge to the academic fields. We developed and evaluated a questionnaire from
      the perspective of traditional Chinese medicine (TCM) that embodies the features
      of TCM syndrome diagnosis for measuring SHS in China. METHODS: The construction
      of the theoretical framework of the questionnaire was based on a literature
      review, an expert questionnaire survey and group interviews. The subscales and
      questionnaire items were screened through a pilot study using statistical means
      and qualitative analysis. Reliability tests that were used included test-retest
      reliability, Cronbach's a coefficient, split-half reliability; validity tests
      included content validity, criterion validity, discrimination validity and
      construct validity. RESULTS: The final questionnaire, the SHSQ-50, included 50
      five-class quantifiable items that encompassed nine subscales: liver stagnation
      syndrome, liver-Qi deficiency syndrome, spleen-Qi deficiency syndrome, liver-fire
      syndrome, heart-fire syndrome, stomach-fire syndrome, heart-Qi deficiency
      syndrome, lung-Qi deficiency syndrome and dampness syndrome. Questionnaires were
      completed by 268 of the 288 SHS subjects (93.0%) and by 86 of the 94 healthy
      subjects (91.5%). The Cronbach a coefficients, split-half coefficients and
      stability coefficients ranged from 0.70 to 0.95, 0.67 to 0.87 and 0.88 to 0.98,
      respectively, for the overall scores and subscales. The Wilcoxon rank test showed
      statistically significant differences in the subscales and overall scores between
      the SHS group and the healthy group (P < 0.01). Twelve factors with an eigenvalue
      greater than one were extracted by factor analysis and merged into nine factors,
      for which the cumulative contribution rate was 63.63%. The nine factors were
      corresponded to the overall structure of the questionnaire. CONCLUSION: The SHSQ
      50 is a reliable and valid instrument for measuring TCM syndrome diagnosis of SHS
      in China.

PMID- 22876434
TI  - Meta-analysis of Chinese medicines for prevention and treatment of radiation
      esophagitis.
AB  - OBJECTIVE: To systematically assess the clinical effectiveness of Chinese
      medicines for prevention and treatment of radiation esophagitis by meta-analysis.
      METHODS: The articles were mainly retrieved from the "CHKD (China Hospital
      Knowledge Database) periodical full text databank", the "China periodical full
      text databank", the "CHKD doctor's and Master's degree student full text
      databank", and the "China doctor's degree student thesis databank", and they were
      selected according to the literature selection standard. The effects of Chinese
      medicines and Western medicines on radiation esophagitis were compared by meta
      analysis. RESULTS: Based on 13 articles, we found that the effectiveness of
      Chinese medicines for prevention and treatment of radiation esophagitis was
      superior to Western medicines, with no obvious side effects. Meta-analysis showed
      that the total odds ratio was 0.426 and the 95% confidence interval was 0.368,
      0.493. CONCLUSION: Chinese medicines are superior to Western medicines in
      preventing and treating radiation esophagitis. However, some methodological
      problems in the literature may have affected the authenticity of the results.
      Therefore, more rigorous, multi-central, randomized controlled trials with a
      large sample size should be designed to obtain a more reliable conclusion.

PMID- 22876435
TI  - Designing and implementing multicenter clinical randomized controlled trials on
      moxibustion with large samples.
AB  - Implementing clinical trials with large multicenter samples is an important way
      to scientifically evaluate and demonstrate the curative effect of moxibustion. At
      present, clinical trials on moxibustion with large multicenter samples are
      prospering in China. It is necessary for research units to have good research
      professionals and technical platforms as well as a highly standardized and
      scientifically feasible methodology of research. Taking tasks in the ongoing
      national 973 project and in the sci-tech support program of the "11th 5-year
      plan", for example, this research captures the characteristics of moxibustion,
      carries out deep analysis and introduces specific methods and the important
      significance of clinical research tasks on moxibustion in designing multicenter
      plans, implementing experiments, supervising quality and strengthening
      compliance.

PMID- 22876436
TI  - Duration of viral shedding of influenza A (H1N1) virus infection treated with
      oseltamivir and/or traditional Chinese medicine in China: a retrospective
      analysis.
AB  - OBJECTIVE: H1N1 was a new and potentially serious infectious disease, in human,
      the severity of influenza can vary from mild to severe, thus to find an effective
      and safety way to control the influenza pandemic is of crucial importance. This
      retrospective study describes the duration of viral shedding in H1N1 patients
      that were hospitalized and treated in China. METHODS: Clinical data were
      collected from May to July, 2009 in China for 963 patients with influenza A
      (H1N1) virus infection. Patients were treated based on the guidelines issued by
      the Chinese Ministry of Health. The primary outcome was duration of viral
      shedding and statistical comparisons were performed. RESULTS: In the patients
      with body temperature greater than 38.0 degrees C, there were no differences in
      virus shedding duration among the patients taking oseltamivir within two days,
      patients undergoing Traditional Chinese Medicine (TCM) therapy or those receiving
      no drug therapy. In patients with body temperature > or =38.1 degrees C, TCM
      therapy reduced the viral shedding duration (P < 0.05, vs. oseltamivir therapy).
      Furthermore, taking oseltamivir two days after onset of symptoms might prolong
      the virus shedding duration (P < 0.05, vs. taking oseltamivir less than 2 days of
      onset). CONCLUSION: TCM therapy is effective for reducing the length of virus
      shedding in patients with body temperature > or =38.0 degrees C. Oseltamivir used
      for reducing virus shedding duration should be taken within two days of onset.

PMID- 22876437
TI  - A traditional Chinese herbal medicine compound preparation versus interventional
      therapy after resection of small hepatocellular carcinoma: 22-year follow-up.
AB  - OBJECTIVE: To compare the long-term effectiveness of compound
      Ruanjianhugan(RJH)tablets and interventional therapy (IT) in patients after
      resection of small hepatocellular carcinoma (HCC). in 399 patients after
      resection of small HCC who were admitted between January 1987 and December 2008
      in the Department of Hepatobiliary Surgery and Center of Minimally Invasive
      Surgery, First Affiliated Hospital of Guangxi Medical University. Four groups
      were based on different therapy modes: a TCM-only (TCMO) group, a TCM combined
      with interventional therapy (TCM-IT) group, an interventional therapy-only (ITO)
      group, and a simple operation (SO) group. Prognostic factors were correlated with
      overall survival (OS) and OS rates were calculated with the Kaplan-Meier method,
      and multivariate analyses for factors affecting survival were evaluated by the
      Cox proportional hazard model. RESULTS: The median OS was 151.20 months in the
      TCM-IT group, 43.87 months in the ITO group, and 20.77 months in the SO group.
      All survival rates of the TCMO group were higher than those of the other three
      groups (>50%). The 5-, 10-, and 15-year OS in the TCMO and ITO patients were
      83.94%, 45.50%, and 71.22% and 33.34%, 55.58%, and 9.26%, respectively (risk
      ratio, 0.209; 95% confidence interval, 0.126-0.347; P = 0.000). Multivariate
      analysis revealed that the independent risk factors were therapy mode (P =
      0.000), sex (P = 0.005), family history (P = 0.011), TNM classification of
      malignant tumor staging (P = 0.000), medical care-seeking behavior (P = 0.021),
      and maximum diameter (P = 0.030). CONCLUSION: Long-term oral use of compound RJH
      tablets may improve OS for small HCC after resection compared with IT.

PMID- 22876438
TI  - A clinical study of weining granules in the treatment of gastric precancerous
      lesions.
AB  - OBJECTIVE: To investigate the clinical effects of Weining granules on gastric
      precancerous lesions (GPLs). METHODS: 120 patients with GPLs were randomly
      assigned in a 1:1 ratio to receive Weining granules (trial group) or the
      comparator Weifuchun tablets (control group) for 6 months. Outcomes were compared
      between the two groups including: overall response; gastroscopically-determined
      response; pathologically-confirmed response; eradication of Helicobacter pylori
      (HP); microvessel density (MVD) in the gastric mucosa; expression of vascular
      endothelial growth factor (VEGF); interleukin 2 (IL-2); interleukin 6 (IL-6); T
      lymphocyte subsets; immunoglobulins; symptom scores; quality of life (QOL); and
      adverse reactions. RESULTS: Patients in the trial group had a significantly
      higher (P < 0.05) overall response rate (81.7%) as compared with those in the
      control group (63.3%). Relative to treatment with Weifuchun tablets treatment
      with Weining granules resulted in a significant improvement (P < 0.05) in the
      scores for gastric pain, distension and stuffiness in the hypochondrium, and
      anorexia. As compared with the tablets the granules were associated with a
      significantly higher overall gastroscopically-determined response rate (78.3%; P
      < 0.05). Pathological examination of tissue samples indicated that 61.7% of
      patients receiving the granules were cured with an overall response rate of
      75.5%; these rates were significantly higher than in the control group (P <
      0.05). In comparison with patients receiving the tablets, those given the
      granules were significantly more likely to have their HP eradicated (75.0% vs.
      51.4%; P < 0.05). Improvements in MVD, VEGF, CD4+, CD4+/ CD8+, IL-2, IL-6 and IgG
      were significantly greater with the Weining Granules than with the Weifuchun
      tablets (P < 0.05 or P < 0.01). After follow-up of 1 year, 17.5% of patients in
      the trial group relapsed as compared with 39.5% in the control group (P < 0.05).
      Relative to the control group, the trial group showed significantly greater
      improvements in physical, psychological and social relationships, and in
      environmental domains (P < 0.05 or P < 0.01). No significant adverse reactions
      were observed during treatment. CONCLUSION: The Weining granules appear to be
      effective in improving the gastric precancerous state and the main symptoms, in
      inhibiting angiogenesis, enhancing immune function and QOL, and in reducing 1
      year relapses. In addition, this preparation seems to be associated with a low
      risk of adverse events, making it a safe and efficacious option for the treatment
      of GPLs.

PMID- 22876439
TI  - Mortality and recurrence of vascular disease among stroke patients treated with
      combined TCM therapy.
AB  - OBJECTIVE: To confirm the long-term outcomes of stroke patients and determine
      predicting factors for death, recurrence of vascular events and poor outcome
      (either recurrence or death) after the use of combined TCM therapy. METHODS: This
      was a retrospective hospital-based cohort study and was performed in the First
      Affiliated Hospital of Tianjin University of Traditional Chinese Medicine in
      Tianjin. All subjects with stroke consecutively admitted to an inpatient ward of
      the Acupuncture Department from January 1, 2008, to December 31, 2008 were
      retrospectively followed through one year. The main outcomes were either a
      recurrence of vascular events, mortality or both. Risk factors were recorded from
      medical records. Multivariate regression models were used to analyze predictors.
      The following independent variables were used: age, gender, hypertension,
      ischemic heart disease, atrial fibrillation, diabetes mellitus, carotid arterial
      lesions and history of stroke. RESULTS: Four-hundred and five patients were
      included. The 1-year mortality rate was 11.11%. 23.70% of the patients had a
      recurrent vascular event, and 30.86% suffered a poor outcome. Multiple logistic
      regression analysis found that previous stroke, and advanced age were predictors
      of death within one year, Recurrence of vascular events was associated with
      carotid arterial lesions, history of diabetes and previous stroke. Long-term poor
      outcome was predicted by advanced age, history of diabetes, and previous stroke.
      CONCLUSION: Age, previous stroke, carotid arterial lesions and diabetes history
      seem to have different impacts on the three outcomes within one year. Our
      findings provide important data for planning future hospital register studies of
      stroke patients in TCM hospitals.

PMID- 22876440
TI  - Prognostic factors for community-acquired pneumonia in middle-aged and elderly
      patients treated with integrated medicine.
AB  - OBJECTIVE: To identify prognostic factors in middle-aged and elderly patients
      with community-acquired pneumonia (CAP) who underwent integrated interventions
      involving traditional Chinese medicine (TCM) and modern medicine. METHODS:
      Patients aged > or =45 years and diagnosed with CAP were divided into a middle
      aged cohort (45-59 years) and an elderly cohort (> or =60 years), and clinical
      data comprising 75 predictor variables in seven classes were collected. After
      replacing missing data, calibrating multicenter differences and classifYing
      quantitative data, univariate and multivariate analysis were performed. RESULTS:
      On multivariate analysis, eight independent risk factors--respiration rate, C
      reactive protein (CRP), cost of hospitalization, anemia, gasping, confusion,
      moist rales and pneumonia severity index (PSI)--were correlated with the outcome
      "not cured" in the elderly cohort. Nine factors--neutrophil percentage (Neu%),
      blood urea nitrogen (BUN), time to clinical stability, appetite, anemia,
      confusion, being retired or unemployed, Gram-negative bacterial infection and
      educational level were correlated with not cured in the middle-aged cohort.
      CONCLUSION: Independent predictive risk factors correlated with adverse outcomes
      in elderly patients were higher respiration rate, CRP > or = four times the mean
      or median for the patient's center, cost of hospitalization >11,323 RMB and PSI
      >11, plus anemia, gasping, confusion and moist rales; those in middle-aged
      patients were higher Neu%, BUN > or = mean or median, loss of appetite, anemia,
      confusion, being retired or unemployed and lower educational level. Gram-negative
      bacterial infection and time to clinical stability >9 days were protective
      factors.

PMID- 22876441
TI  - The infrared radiation spectrum of acupoint taiyuan (LU 9) in asthma patients.
AB  - OBJECTIVE: To analyze the distinctive pathological characteristics in the
      spectrums of spontaneous infrared radiation at the Taiyuan (LU 9) acupoint in
      patients with asthma. METHODS: A highly sensitive infrared spectrum detecting
      device was used to detect the spectrums of spontaneous infrared radiation at
      Taiyuan (LU 9) in 37 asthma patients and 34 healthy volunteers. RESULTS: Asthma
      patients had significantly lower infrared intensity than that of the healthy
      volunteers (P>0.01). Asthma patients had significantly lower overall infrared
      radiation intensity at the left Taiyuan (LU 9) than that of healthy volunteers (P
      > 0.05), but there was no significant difference between healthy volunteers and
      asthma patients at the right Taiyuan (LU 9) (P > 0.05). The infrared radiation
      intensity of 17 wavelength spots at the left Taiyuan (LU 9) and 4 wavelength
      spots at the right Taiyuan (LU 9) in asthma patients were significantly lower
      than those of healthy volunteers (P > 0.05). At 2 microm, the infrared radiation
      intensity of asthma patients was significantly stronger than that of healthy
      volunteers (P > 0.05). At 19 wavelength spots in the healthy volunteers and at 4
      wave-length spots in the asthma patients, the left Taiyuan (LU 9) showed a
      significantly stronger intensity than that of the right Taiyuan (LU 9) (P >
      0.05S). By Pearson's chi2 test, healthy volunteers had more wavelength spots that
      were significantly different between the left and right Taiyuan (LU 9) than the
      asthma patients (P > 0.01). CONCLUSION: Changes in the infrared spectrum at the
      Taiyuan (LU 9) acupoint in asthma patients may reflect distinct pathological
      changes. Certain acupuncture points may be related to specific organs.

PMID- 22876442
TI  - Protective effects of modified linggui zhugan decoction combined with short-term
      very low calorie diets on cardiovascular risk factors in obese patients with
      impaired glucose tolerance.
AB  - OBJECTIVE: To observe the protective effects of modified Linggui Zhugan decoction
      combined with short-term very low calorie diets (VLCDs) on cardiovascular risk
      factors in obese patients with impaired glucose tolerance (IGT). METHODS: Eighty
      five obese patients with IGT of spleen hypofunction and dampness accumulation
      type were randomly divided into treated group (n=45)and control group (n=40). The
      treated group was given Linggui Zhugan decoction combined short-term VLCDs. The
      control group was given basic weight-reduction treatment. The total course was 6
      months. Changes of fasting plasma glucose (FPG), 2-hour postprandial blood
      glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), lipid
      metabolism, blood pressure, body mass index (BMI) and waist circumference (WC)
      were observed, and the outcomes were reviewed after the treatment. RESULTS:
      Compared with the control group, the levels of FPG, 2 hPG, HbA1c, FINS, HOMA-IR
      decreased significantly (P < 0.05), and the indexes of total cholesterol (TC),
      triglyceride (TG), low-density lipoprotein (LDL), systolic blood pressure (SBP),
      diastolic blood pressure (DBP), BMI and WC were improved significantly (P < 0.05)
      in the treated group. The transformation rate of normal glucose tolerance (NGT)
      was higher in treatment group than control group (P < 0.01). No severe adverse
      reaction was found in the therapeutic course. CONCLUSION: The modified Linggui
      Zhugan decoction combined with short-term VLCDs has good protective effects on
      cardiovascular risk factors as a treatment intervention for IGT with obesity, as
      it could improve glycometabolism, significantly decrease the levels of blood
      pressure, blood lipids, BMI, WC and effectively cut-off and reverse the
      development of diabetes mellitus.

PMID- 22876443
TI  - Influence of acupuncture on cognitive function and markers of oxidative DNA
      damage in patients with vascular dementia.
AB  - OBJECTIVE: To test the influence of acupuncture on cognitive function and a
      marker of oxidative DNA damage in patients with vascular dementia (VD). METHODS:
      Sixteen VD patients were evaluated before and after acupuncture, using the
      Folstein mini-mental state examination-revised (MMSE-R) to assess cognitive
      function, and the ADL-R scale to assess independence in activities of daily
      living (ADL). Life quality was evaluated using the DEMQOL (Dementia quality of
      life questionnaire) questionnaire, and syndromes and expression of vascular
      dementia were evaluated with the Scale for the differentiation of syndromes of
      vascular dementia (SDSVD). In addition, the urine concentration of 8-hydroxy-2'
      deoxyguanosine (8-OHdG)--a marker of oxidative damage--was quantified with enzyme
      linked immunosorbent assay. RESULTS: The MMSE-R and DEMQOL scores were higher
      after acupuncture than before (P < 0.05), while there were no obvious differences
      in the ADL-R or SDSVD scores (P > 0.05). The 8-OHdG content in urine
      significantly decreased after acupuncture (P < 0.05). CONCLUSION: Acupuncture
      reduces the levels of 8-OHdG and improves cognitive function and quality of life
      in VD patients, suggesting that acupuncture is beneficial at least in part by
      preventing oxidative damage.

PMID- 22876444
TI  - The effects of Chinese yam-epimedium mixture on respiratory function and quality
      of life in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To examine the clinical effects of a mixture of Chinese Yam and
      epimedium in patients with stable moderate or severe chronic obstructive
      pulmonary disease (COPD). METHODS: Forty-nine patients with COPD were randomly
      allocated to a group whose usual treatment was supplemented with oral Chinese yam
      epimedium mixture, or a control group given placebo. For each patient, body mass
      index, airflow obstruction, dyspnea, and exercise capacity were measured and
      converted into the BODE index before treatment and at one and three months after
      initiation of treatment. Participants also completed the St. George's respiratory
      questionnaire (SGRQ) at the same intervals. RESULTS: After one month,
      improvements were seen in the BODE index and SGRQ of participants taking Chinese
      yam-epimedium mixture compared to controls. There were statistically significant
      differences in the SGRQ: three of its components and the total SGRQ scores were
      significantly decreased (P < 0.05), respiratory symptom scores had improved (P <
      0.01), and the dyspnea component of the BODE index had significantly decreased (P
      < 0.05). Similar improvements were observed after three months of treatment, but
      exercise tolerance had also improved: the six-minute walking distance had
      significantly increased (P < 0.05) in the treatment group when compared with
      controls. CONCLUSION: Chinese yam-epimedium mixture can significantly improve
      dyspnea, exercise capacity, and the quality of life of patients with stable
      moderate or severe COPD.

PMID- 22876445
TI  - Research on fuzi based on animal thermotropism behavior to discover if it has
      fewer "hot" characteristics without Ganjiang.
AB  - OBJECTIVE: To investigate whether fuzi (Radix Aconiti Praeparata) has fewer "hot"
      characteristics when administered without Ganjiang (Rhizoma Zingiberis). METHODS:
      Differences in the thermotropism behaviors of mice treated either with fuzi
      (Radix Aconiti Praeparata), Ganjiang (Rhizoma Zingiberis) or the combination of
      the two given intragastrically were investigated using the Animal Thermotropism
      Behavior Surveillance System. The water intake volume, oxygen consumption volume,
      adenosine triphosphatase (ATPase) activity, total antioxidant capacity (T-AOC)
      and total superoxide dismutase (T-SOD) activity were determined during the
      investigation. RESULTS: When fuzi and ganjiang were administered together, the
      rate at which mice remained on a warm plate ("remaining rate") and the times and
      distances of their movement were all significantly reduced (P < 0.05). Compared
      with the Normal group, the reduction was 55.1%, 48.3% and 44.8%, while compared
      with the Fuzi group, the reduction was 57.6%, 34.3% and 36.0%, indicating that
      "cold" tropism was significantly increased. Compared with the normal and fuzi
      groups, the ATPase activity and the respiratory oxygen consumption volume of the
      fuzi + ganjiang group were significantly increased (P < 0.05), suggesting an
      improvement in energy metabolism and showing a "hot" characteristic when Fuzi and
      Ganjiang are present together. Additionally, the T-AOC and T-SOD activity were
      significantly enhanced (P < 0.05). CONCLUSION: The behavior of mice tending
      toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having
      fewer characteristics consistent with a "hot" nature when not used with Ganjiang,
      the functional mechanism of which may be a change in the ATPase activity in liver
      tissue.

PMID- 22876446
TI  - Functional mechanism of pingchuanning decoction on adjustment of Clara cell
      secretory protein in airway remodeling of asthmatic rats.
AB  - OBJECTIVE: To study the functional mechanism of pingchuanning decoction in
      treatment of airway remodeling in asthmatic rats. METHODS: Eighty healthy Wistar
      male rats were randomized into eight groups (n=10 rats each): Normal group,
      asthma model group, dexamethasone group, guilong kechuanning group, xiaoqinglong
      decoction group, and pingchuanning decoction low-, middle-, and high-dose groups.
      The rats of all but the normal group were made into asthma models through
      intraperitoneal injection and aerosol inhalation of ovalbumin. All treatments
      were administered at the first stimulation of asthma onset (third week of
      modeling), and the rats were killed after stimulating asthma attacks for 4 weeks.
      The general conditions of rats and pathomorphological changes of the lung tissues
      were observed. The expression of nerve growth factor (NGF) of the lung tissues
      was measured with immunohistochemical methods, and the content of clara cell
      secretory protein (CCSP) mRNA was determined with RT-PCR. RESULTS: Compared with
      the normal group, the contents of NGF and CCSP mRNA in the lung tissues of the
      model group were significantly changed (P < 0.01). Compared with the model group,
      the indices of pingchuanning decoction and other treatment groups were improved
      to some extent (P < 0.05 or P < 0.01). CONCLUSIONS: Pathological changes of
      airway inflammation and remodeling were present in these rat asthma models.
      Pingchuanning decoction had an intervention effect on these experimental models.
      Its functional mechanism may be related to multiple factors, including
      alleviation of airway inflammation, relief of bronchial smooth muscle spasm, and
      inhibition of airway remodeling.

PMID- 22876447
TI  - Inhibition of hypoxia and serum deprivation-induced apoptosis by salvianolic acid
      in rat mesenchymal stem cells.
AB  - OBJECTIVE: To investigate the influence and mechanism of salvianolic acid B
      (SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells
      (BMSCs) induced by hypoxia and serum deprivation (hypoxia/SD). METHODS: SalB
      concentration of 0.1, 1, 10 or 100 mg/L (drug groups) were investigated for their
      ability to inhibit apoptosis in rat BMSCs. BMSCs in both the apoptosis model and
      drug groups were cultured under hypoxic conditions for 6 h, after which cell
      apoptosis and change in mitochondrial membrane potential (MMP) were detected
      using flow cytometry. Activation of caspase-3 was detected using western blot
      analysis. RESULTS: Hypoxia/SD induced apoptosis in rat BMSCs. The early apoptosis
      rate was lower in the drug groups compared to the apoptosis model group (P <
      0.05). SalB was found to inhibit the reduction in MMP and decrease the activation
      of caspase-3. CONCLUSION: 0.1, 1 and 10 mg/L of SalB inhibits activation of
      caspase-3 and early apoptosis of rat BMSCs induced by hypoxia/SD and could
      therefore enhance the survival rate of grafted stem cells.

PMID- 22876448
TI  - The effects of kangxianling on renal fibrosis as assessed with a customized gene
      chip.
AB  - OBJECTIVE: To determine the mechanisms by which kangxianling (KXL) treats renal
      interstitial fibrosis using a customized gene chip. METHODS: Twelve out of 18
      specific pathogen-free sprague dawley (SPF SD) rats underwent a unilateral
      ureteral occlusion. These rats were then randomly assigned into either the model
      unilateral ureteral obstruction (UUO) or kangxianling (KXL) group. The other six
      rats were assigned to the sham-operated group. The UUO and sham-operated groups
      were given normal saline via intragastric administration, whereas the KXL group
      was given KXL via intragastric administration. All rats were sacrificed for renal
      tissue collection (i.e., left nephridial tissue), and the detection of genetic
      changes with the customized chip. RESULTS: Compared to the sham-operated group,
      transforming growth factor-beta (TGF-beta), Smad2, and Smad3 genes were
      significantly up-regulated in the UUO group, with >1.5-fold rise (P < 0.01). The
      Smad7 gene was significantly reduced in the UUO versus sham-operated group, with
      a down-regulation of >1.5-fold (P < 0.01). In the KXL group, TGF-beta1, Smad2,
      and Smad3 genes were significantly reduced compared to the UUO group, with a down
      regulation of >1.5-fold (P < 0.01), whereas the Smad7 gene was significantly
      increased compared to the UUO group, with an up-regulation of > 1.5-fold (P <
      0.01). CONCLUSION: It was found that KXL can significantly reduce the gene levels
      of TGF-beta1, Smad2, and Smad3. Immunohistochemistry findings also revealed
      significantly lower TGF-beta1/Smads-mediated gene transcription activity. These
      findings suggest that KXL may negatively regulate the TGF-beta1/Smads signal
      pathway to inhibit the occurrence of renal fibrosis.

PMID- 22876449
TI  - Inflammatory responses of the rat lungs in cold-dryness syndrome in the northwest
      of China.
AB  - OBJECTIVE: To examine changes in body weight and the lung inflammation factors
      interleukin-1beta (IL-1beta), interleukin-8 (IL-8), IL-10 and tumor necrosis
      factor-alpha (TNF-alpha) in a rat model of cold-dryness syndrome in Northwest
      (Xinjiang) China to provide a reference for treating chronic obstructive
      pulmonary disease (COPD) with local peculiarities. METHODS: The rat COPD model
      was established by intratracheal instillation of porcine pancreatic elastase
      (PPE) in combination with cigarette smoking (CS). The rat model of cold-dryness
      syndrome of COPD in the northwest of China was set up by intratracheal
      instillation of PPE in combination with CS and environmental cold-dryness stress.
      The level of IL-1beta, IL-8, IL-10 and TNF-alpha in bronchoalveolar lavage fluid
      (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The data were
      analyzed using the software SPSS 11.5. RESULTS: (1) Body weight was less in the
      two model groups than that of control group (P < 0.01), PPE plus CS cold-dryness
      group was less than that of PPE plus CS group (P < 0.01). (2) IL-1beta in BALF
      significantly increased in PPE plus CS and cold-dryness group than that of
      control group (P < 0.01). (3) IL-8 and TNF-alpha in BALF significantly increased
      in PPE plus CS and cold-dryness group and PPE plus CS group than that of control
      group (P < 0.01). CONCLUSION: Body weight in COPD model rats was reduced compared
      with controls. Cold-dryness may aggravate such a condition lung inflammation in
      the model was mainly manifested by an increase in IL-1beta, IL-8 and TNF-alpha
      levels, with no change in IL-10 levels. Cold-dryness may aggravate lung
      inflammation of COPD.

PMID- 22876450
TI  - Influences of electro-acupuncture at related jing-well points in rats with
      vascular dementia.
AB  - OBJECTIVE: To observe the effects of electro-acupuncture (EA) at related Jing
      well Points (HT 9, PC 9, KI 1 and LU 11) in rats with vascular dementia (VD) and
      discuss the relative mechanism. METHODS: A randomized controlled animal
      experiment was designed. A total of 104 rats were involved in the present study
      and divided randomly into 4 groups: sham-operation group, model group, Jing-well
      Points group, and medication group. The VD model was established according to the
      modified 4-vessel occlusion (4-VO) method. VD rats in the Jing-well Points group
      were treated by EA at the related Jing-well Points (HT 9, PC 9, KI 1 and LU 11)
      while those in the medication group were treated with nimotop. The step-down
      avoidance test was performed before and after treatment in all rats. Latency and
      error frequency indexed memory function were recorded. Nitric oxide (NO) levels
      and superoxide dismutase (SOD) activity in both cerebral tissue and serum were
      detected after the treatment course. RESULTS: A total of 42 rats were included in
      the final analysis. Compared with the model group, the latency in the Jing-well
      Points group was significantly prolonged (P < 0.01) and the error frequency was
      significantly decreased (P < 0.05) after therapy; the decrease in NO levels in
      both brain tissue and serum was significant (P < 0.05 and P < 0.01,
      respectively); and the increase in SOD activity was also significant (P < 0.01).
      There was no significant difference in latency, error frequency, NO levels and
      SOD activity between the Jing-well Points group and medication group. CONCLUSION:
      EA at related Jing-well Points can remarkably improve memory impairment in VD
      rats. Moreover, decreasing the overproduction of NO and strengthening the ability
      of eliminating free radicals may provide therapeutic potential for the treatment
      of VD.

PMID- 22876451
TI  - Effects of hydroxy safflower yellow-A on tumor capillary angiogenesis in
      transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice.
AB  - OBJECTIVE: To study the effects of hydroxy safflower yellow A (HSYA) on tumor
      capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823
      tumors in nude mice. METHODS: BGC-823 cells were injected subcutaneously into the
      right anterior armpit of nude mice to establish an animal model of transplanted
      tumors. After 24 h, 18 nude mice injected with tumor cells were randomized into
      model, control, and HSYA 0.028 g/L groups, with six mice in each group.
      Transplanted tumors were excised on day 20. Tumor inhibition ratios were
      calculated for the transplanted tumors. Pathological changes and capillary
      angiogenesis in the tumors were observed by light microscopy. RESULTS: Tumors in
      the model group grew more quickly than those in the control and HSYA groups, with
      inhibition ratios of 48% and 30%, respectively. The microvessel count in the HSYA
      group was lower than in the model group (P < 0.01), and microvessel density was
      also lower in the HSYA group (P < 0.05). Pathological changes were more obvious
      in tumors in the model group compared to the HSYA group. CONCLUSION: HSYA
      inhibits the growth of transplanted BGC-823 tumors, and its effects on tumor
      capillary angiogenesis may represent one of the mechanisms responsible for this
      antineoplastic effect.

PMID- 22876452
TI  - Experimental research into using bone-strengthening pill to treat ischemic
      necrosis of femoral head.
AB  - OBJECTIVE: To study the use of a bone-strengthening pill to treat ischemic
      necrosis of the femoral head. METHODS: A model of castration in rats with
      osteoporosis and a model of ischemic necrosis in the bilateral femoral heads of
      young rats were used to detect bone density, bone formation measurements, lipid
      deposition in the femoral head, the distribution of capillaries in the femoral
      head and other relevant biochemical indices. RESULTS: In model rats, bone
      strengthening pills were able to increase the bone density, the unit volume of
      bony trabeculae, the width of bony trabeculae, and the unit volume of the bony
      cortex. They could also enhance the mineral apposition rate in the femoral head
      and the seam width of osteoid deposition. Furthermore, there was a reduction in
      lipid deposition in the femoral head, and enriched distribution of arteries in
      the femoral head. Bone-related biochemical detections showed an increase in
      alkaline phosphatase staining and a decrease in tartaric acidic phosphatase
      staining. CONCLUSION: The results show that bone-strengthening pills can
      obviously promote bony growth, cause an increase in bone density, restore blood
      circulation, inhibit the occurrence and development of bony necrosis, and
      accelerate the repair of necrotic bones, with no toxic side-effects.

PMID- 22876453
TI  - Effects of cold-damp and hot-damp environment on VEGF and IL-1 expression in
      joint cartilage cells in adjuvant arthritis in rats.
AB  - OBJECTIVE: To study the effects of environmental factors on the degree of injury
      and expression of vascular endothelial growth factor (VEGF) and interleukin-1 (IL
      1) in cartilage cells of the joint in a rat model of adjuvant arthritis (AA).
      METHODS: SD rats aged 10 months were randomly divided into 4 groups that varied
      by temperature and humidity housing conditions and induction of AA: a control
      group, a model group, a cold-damp group, and a hot-damp group. All groups except
      the control group were induced with AA. After 4 w, VEGF and IL-1 expression in
      cartilage cells of ankle joints of hind limbs were observed. RESULTS: Mean area,
      optical density, and numbers of VEGF- and IL-1-positive cells in the model group,
      the cold-damp group, and the hot-damp group were significantly higher than that
      of the control group (all P < 0.05). Optical density and positive cell numbers in
      the cold-damp group and the hot-damp group were significantly higher than that of
      the model group (all P < 0.05). Optical density and positive cell numbers in the
      hot-damp group were significantly higher than that of the cold-damp group. Bone
      in the hot-damp and cold-damp groups was severely injured. CONCLUSION:
      Environmental factors such as high humidity combined with either high or low
      temperature increase the severity of damage and expression of VEGF and IL-1 in
      cartilage cells of joints in rats induced with AA.

PMID- 22876454
TI  - Actions of four organic acids in radix isatidis on endotoxin-neutralization
      investigated by kinetic turbidimetric assay.
AB  - OBJECTIVE: To investigate anti-endotoxin action of four OAs reacted with
      endotoxin by the LAL assay with KTA. METHODS: Using a incubating kinetic tube
      reader and kinetic turbidimetric assay (KTA), the concentration-response time
      curve of endotoxin reacted with limulus amebocyte lysate (LAL) at 37 degrees C
      were obtained and the action of four organic acids (OAs) on it were investigated.
      The four OAs were benzoic acid, salicylic acid, syringic acid and 2-amino-benzoic
      acid from Radix isatidis. Meanwhile, the temperature variation caused by
      endotoxin with the four OAs was studied by the rabbit pyrogen test (RPT).
      RESULTS: It was showed that a low concentration (1 mg/mL) of the four OAs had a
      little effect of anti-endotoxin, and when the concentrations of the four OAs were
      30 mg/mL, the endotoxin was neutralized completely. The relationships between the
      concentrations of endotoxin and the OAs were all linear with correlation
      coefficients of greater than 0.9995, indicating that the four OAs all had strong
      anti-endotoxin action, while syringic acid had the strongest action among the
      four OAs with IC50 of 12.84 mg/mL. CONCLUSION: The investigations of KTA agreed
      well with the results obtained by means of RPT.

PMID- 22876455
TI  - Effects of Wenxiao II decoction on the expression of MCP-1 and VCAM-1 in
      atherosclerotic rabbits.
AB  - OBJECTIVE: To observe the effects of different doses of wenxiao II decoction on
      the expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell
      adhesion molecule-1 (VCAM-1) in an experimental model of atherosclerosis in
      rabbits and to explore the mechanism by which it alleviates atherosclerosis.
      METHODS: Sixty 3-4 month-old New Zealand rabbits of both sexes were randomly
      divided into six groups: simvastain; model; blank; and high-dose, mid-dose, and
      low-dose wenxiao II decoction groups. Except for those in the blank group, all
      rabbits were fed a high-cholesterol diet. Carotid atherosclerosis was established
      by balloon-induced injury to the endothelium of the carotid artery in conjunction
      with consumption of a high-cholesterol diet. After 8 weeks, all rabbits were
      killed to evaluate the expression of MCP-1 and VCAM-1 by immunohistochemical
      staining. RESULTS: Expressions of MCP-1 and VCAM-1 were significantly decreased
      in all groups except the blank group compared with the model group (P < 0.05).
      When compared with the simvastain group only variation of MCP-1 expression in low
      dose group was not appreciable, and the differences were indistinct (P < 0.05).
      When comparing among wenxiao II decoction groups, MCP-1 expression in the mid-
      and high-dose groups was significantly lower than that seen in the low-dose group
      (P< 0.01), but there were no differences among three dosage groups with respect
      to VCAM-1 expression (P > 0.05). CONCLUSION: These data suggested that high, mid,
      and low doses of Wenxiao II Decoction can inhibit the expression of MCP-1 and
      VCAM-1, which may prevent the formation of or stabilize atherosclerotic plaques.
      There may be a direct relationship between the dosage of wenxiao II decoction and
      its therapeutic efficacy.

PMID- 22876456
TI  - Effect of yishen huayu fang on kidney tissue E-cadherin expression in unilateral
      ureter ligation in rats.
AB  - OBJECTIVE: To observe E-calcium sticky protein (E-cadherin) expression in kidney
      tissues in a rat model of unilateral ureter ligation and the effect of Yishen
      Huayu Fang (formula of tonifying the kidney and dissolving accumulated blood
      stasis) on the expression. METHODS: A total of 150 clean grade male rats were
      randomly divided into a control group, model group, low-dose Yishen Huayu Fang
      group (low-dose group), high-dose Yishen Huayu Fang group (high-dose group), and
      Lotensin group. A renal fibrosis model was established with unilateral ureteral
      obstruction (UUO). Pathological changes of rat renal tissue were observed with
      light microscopy on days 3, 7, 14, 21, and 28 after UUO. Changes in kidney tissue
      E-cadherin expression were observed with immunohistochemistry. RESULTS: Three
      days after modeling, kidney edema appeared followed by gradual inflammatory cell
      infiltration, and part of the small tubules disappeared while the renal cortex
      thinned. Meanwhile, the E-cadherin expression level dropped, which was negatively
      correlated with the obstruction time. After intervention, E-cadherin expression
      was increased in all treatment groups (P < 0.01 or P < 0.05), while there were no
      significant differences between the high-dose and Lotensin groups. CONCLUSION:
      Yishen Huayu Fang delays the renal fibrosis process by promoting E-cadherin
      expression in renal tissues and reducing extracellular matrix deposition.

PMID- 22876457
TI  - Relationship between urinary nephrin and urinary albumin changes in diabetic rats
      and effects of yiqiyangyinhuayutongluo recipe.
AB  - OBJECTIVE: To investigate the dynamic changes of urinary nephrin, and the
      relationship between it and urinary albumin excretion rate (UAER) in a diabetic
      rat model, as well the effects of yiqiyangyinhuayutongluo recipe. METHODS:
      Diabetic model was induced by high fat diet combined with low-dose Streptozotocin
      (STZ) in rats. Normal group (NG), model group (MG), and yiqiyangyinhuayutongluo
      recipe treated group (YHTG) were set. Gastrointestinal Yiqiyangyi-nhuayutongluo
      recipe was administered once daily for 32 w. At the end of the 2nd w (2 w), 8 w,
      16 w, and 32 w, fasting blood glucose (FBG), UAER and 24h urinary nephrin (U
      nephrin) were detected. RESULTS: Compared with NG, FBG in MG increased notably (P
      < 0.05). Compared with MG, FBG of YHTG (P < 0.05) since 16 w. U-nephrin and UAER
      in MG increased significantly from 2 w, peaked at 16 w, lessened in different
      degree at 32 w, but were still higher than NG. The correlation analysis showed
      that there was a significant positive correlation between U-nephrin and UAER at
      different time, the correlation coefficient as r > 0.9, and P < 0.05. Compared
      with MG, U-nephrin and UAER in YHTG decreased markedly (P < 0.05) except for U
      nephrin at 8 w. CONCLUSIONS: U-nephrin and UAER in diabetic rat model have a
      positive linear correlation. Yiqiyangyinhuayutongluo recipe can reduce UAER
      markedly, and preventing the lose of nephrin in urine maybe one of the
      mechanisms.

PMID- 22876458
TI  - Effects of ningdong granule on DA, DRD2, and HVA in a rat model of Tourette's
      syndrome.
AB  - OBJECTIVE: Ningdong granule is a traditional Chinese medicine preparation for the
      treatment of Tourette's syndrome. METHODS: Sixty-four rats were randomly assigned
      to a control group and three experimental groups, respectively. Rat models of
      Tourette's syndrome were established via intraperitoneal injection of apomorphine
      (Apo). The rats in the experimental groups were subsequently intragastrically
      injected with haloperidol at 10 mg/kg (haloperidol group), ningdong granule at
      370 mg/kg (NDG group), and normal saline (0.9%) at 10 mL/kg (Apo group),
      respectively. Rat behaviors were observed and recorded on a daily basis. After 12
      w, all rats were sacrificed, and sera and striatal tissues were harvested.
      Homovanillic acid levels in sera, as well as dopamine and dopamine D2 receptor
      mRNA expression in the striatum, were measured to determine possible mechanisms
      of Ningdong granule on the dopamine system in a rat model ofTourette's syndrome.
      RESULTS: Following intervention, stereotype actions of the Tourette's syndrome
      rats were significantly inhibited in the haloperidol and NDG groups, respectively
      (P < 0.01). Homovanillic levels were significantly greater in the haloperidol and
      NDG groups, respectively (P < 0.05). In addition, dopamine levels were
      significantly less in the NDG group (P < 0.01), and DRD2 mRNA expression was
      significantly reduced in the haloperidol and NDG groups, respectively (P < 0.05).
      CONCLUSION: Results demonstrated that Ning-dong granule effectively inhibited
      stereotype actions and Tourette's syndrome symptoms by promoting dopamine
      metabolism, reducing dopamine levels in the striatum, increasing homovanillic
      acid content in sera, and reducing mRNA expression of DRD2 in the striatum.

PMID- 22876459
TI  - Potential advantages of a combination of chinese medicine and bone marrow
      mesenchymal stem cell transplantation for removing blood stasis and stimulating
      neogenesis during ischemic stroke treatment.
AB  - Combined treatment of ischemic stroke with Chinese medicine and exogenous bone
      marrow mesenchymal stem cell (BMSC) transplantation may improve the removal of
      blood stasis and stimulation of neogenesis. Chinese medicines that remove blood
      stasis not only promote blood circulation but also calm the endopathic wind,
      remove heat, resolve phlegm, remove toxic substances and strengthen body
      resistance. The medicinal targeting effect of Chinese medicine can promote the
      homing of BMSCs, and the synergistic therapeutic effects of drugs can contribute
      to BMSC differentiation. As such, exogenous BMSC transplantation has potential
      advantages for neogenesis. Chinese medicines and exogenous BMSCs provide
      complementary functions for the removal of blood stasis and tion of Chinese
      medicine and transplantation of exogenous BMSCs may be particularly suited to
      ischemic stroke treatment.

PMID- 22876460
TI  - Understanding the viscera-related theory that the lung and large intestine are
      exterior-interiorly related.
AB  - Pairing of the viscera and bowels is an important theory, which provides guidance
      to traditional Chinese medicine (TCM) clinical practice. Investigating this
      theory has been the focus of research on the basic theory of TCM. Recently,
      researchers have performed many studies on the theory that the lung and large
      intestine are exterior-interiorly related, which is a different point of view to
      that of previous literature, recent clinical studies and experimental studies,
      and these recent studies have enforced the theoretical connotation of the
      statement. However, there are problems in some of these studies including recent
      clinical studies and experimental studies. In the current article, literature on
      the viscera-related theory of the lung and large intestine are exterior
      interiorly related is reviewed from physiological, pathological, and clinical
      views, and some opinions on the current research status are discussed.

PMID- 22876461
TI  - [Pregnancy with reservations].

PMID- 22876462
TI  - [All records were broken. Impressions the 10th German Down syndrome sports
      festival in Frankfurt].

PMID- 22876463
TI  - [Which deliveries should be selected for quality evaluation of out of clinic
      births].

PMID- 22876464
TI  - [Erythema infectiosum - (not) a harmless (childhood) illness?].

PMID- 22876465
TI  - [Parent group in neonatology. Responsibilities and outcomes].

PMID- 22876466
TI  - ["Everything is only about my brother - and what will become of us?"
      Psychological status of healthy siblings of children with cancer].

PMID- 22876467
TI  - [Soccer as a good thing: 15-year-old Jonas organizes a soccer tournament despite
      progressive muscular dystrophy].

PMID- 22876468
TI  - [Specialty nursing personnel as a scarce commodity in Germany].

PMID- 22876469
TI  - [Presentation of the first pediatric hospice seal in Germany: Balthasar pediatric
      and youth hospice in Olpe is evaluated by Rhineland TUV].

PMID- 22876470
TI  - [How the food industry is turning children into junkfood junkies and is the cause
      of malnutrition - foodwatch report and market check of 1,500 products for
      children introduced this year]].

PMID- 22876471
TI  - [Vitamins in toothpaste to control malnutrition symptoms? Scientists study the
      effectiveness of vitamin B 12 fortified toothpaste].

PMID- 22876472
TI  - [Social justice: what help is available?].

PMID- 22876473
TI  - [Masked strabismus - what is hidden in back of it? "Phoria", does it exist at
      all?].

PMID- 22876474
TI  - [Nature disappears from children's books: buildings increasingly replace forests
      and animals].

PMID- 22876476
TI  - Treatment of bleach pulp mill effluent by MF-MBR.
AB  - The types of treatment most commonly used by pulp mills are biological treatments
      in combination with sedimentation or coagulation/flocculation as pretreatment.
      The main issues faced by these types of treatment are low efficiency in the
      removal of organic matter and the loss of aggregate value for the recovered
      fiber. Therefore, this study aims to evaluate the use of microfiltration (MF)
      combined with a membrane bioreactor (MBR) for the treatment of bleach pulp mill
      effluents. The results showed that the use of the MF-MBR system was an excellent
      alternative for the treatment of bleach pulp mill effluents with an average COD
      removal of 95%. The microfiltration allowed the recovery of fibers, which can be
      returned to the production process without losing economic value, and produced a
      better quality effluent for further treatment in the MBR. The MBR presented high
      efficiency removal of organic matter.

PMID- 22876477
TI  - Carbamazepine degradation by photolysis and titanium dioxide photocatalysis.
AB  - We investigated the degradation of carbamazepine by photolysis/ultraviolet (UV)-C
      only and titanium dioxide photocatalysis. The degradation of carbamazepine by UV
      only and titanium-dioxide-only (adsorption) reactions were inefficient, however,
      complete degradation of carbamazepine was observed by titanium dioxide
      photocatalysis within 30 min. The rate of degradation increased as initial
      carbamazepine concentration decreased, and the removal kinetics fit well with the
      Langmuir-Hinshelwood model. The addition of methanol, a radical scavenger,
      decreased carbamazepine removal, suggesting that the hydroxide radical played an
      important role during carbamazepine degradation. The addition of oxygen during
      titanium dioxide photocatalysis accelerated hydroxide radical production, thus
      improving mineralization activity. The photocatalytic degradation was more
      efficient at a higher pH, whereas the removal of carbamazepine and acridine (a
      major intermediate) were more efficient under aerobic conditions. The
      mineralization of carbamazepine during photocatalysis produced various ionic by
      products such as ammonium and nitrate by way of nitrogen dioxide.

PMID- 22876479
TI  - Effects of nano-copper(II) oxide and nanomagnesium oxide particles on activated
      sludge.
AB  - Effects of nano-copper(II) oxide (nano-CuO) and nanomagnesium oxide (nano-MgO)
      particles on activated sludge endogenous respiration (aerobic digestion),
      biochemical oxygen demand (BOD) biodegradation, and nitrification were
      investigated through respiration rate measurement. For comparison, the effects of
      Cu(II) and Mg(II) ions on activated sludge were also studied. Results indicated
      that soluble Cu(II) has half maximum inhibitory concentration (IC50) values of
      19, 5.5, 53, and 117 mg Cu/L for endogenous respiration, BOD biodegradation,
      ammonium oxidation, and nitrite oxidation, respectively. However, nano-CuO only
      inhibited BOD biodegradation at 240 mg Cu/L or more, and its associated toxicity
      was primarily caused by soluble Cu(II). In contrast, soluble Mg(II) was not toxic
      to activated sludge in the experimental concentration range, but nano-MgO
      inhibited BOD biodegradation and nitrification with IC50 values of 70 and 143 mg
      Mg/L, respectively. Further study indicated that the toxicity of nano-MgO
      resulted primarily from increased pH following MgO hydrolysis.

PMID- 22876478
TI  - Adsorption of microcystin-LR from water with iron oxide nanoparticles.
AB  - Adsorption of microcystin-LR (MC-LR) from water using iron oxide (alpha-Fe2O3)
      nanoparticles was investigated in this study. Adsorption of MC-LR adsorption was
      well-described by a pseudo second order kinetics model and Freundlich and
      Langmuir isotherm equations at 15 to 35 degrees C. Thermodynamic analysis showed
      that the Gibbs free energy was negative, whereas standard enthalpy and entropy
      changes were positive at this temperature range. These findings suggest that the
      adsorption of MC-LR on iron oxide nanoparticles was spontaneous and endothermic.
      The effects of initial pH, inorganic cations, and competing compounds with
      carboxyl groups on absorption of MC-LR were also evaluated. Typically, adsorption
      efficiency decreased with increasing pH from 2 to 11. Sodium ions did not appear
      to significantly affect MC-LR adsorption, whereas calcium ions slightly enhanced
      the MC-LR adsorption capacity of the iron oxide nanoparticles. Moreover, the
      inhibiting effect of competing organic compounds was increased with increasing
      numbers of carboxyl groups, as follows: citric acid (3)>oxalic acid (2)>benzoic
      acid (1).

PMID- 22876480
TI  - Comparative mesophilic and thermophilic anaerobic digestion of palm oil mill
      effluent using upflow anaerobic sludge blanket.
AB  - The effects of organic loading rate and operating temperature on the microbial
      diversity and performances of upflow anaerobic sludge blanket (UASB) reactors
      treating palm oil mill effluent (POME) were investigated. The following two UASB
      reactors were run in parallel for comparison: (1) under a mesophilic condition
      (37 degrees C) and (2) under a mesophilic condition in transition to a
      thermophilic condition (57 degrees C). A polymerase chain reaction (PCR)-based
      denaturing gradient gel electrophoresis (DGGE) analysis showed that the microbial
      population profiles significantly changed with the organic loading rate (OLR) and
      the temperature transition from the mesophilic to the thermophilic condition.
      Significant biomass washout was observed for the mesophilic UASB when operating
      at a high organic loading rate (OLR) of 9.5 g chemical oxygen demand (COD)/L.d.
      In contrast, the thermophilic UASB can be operated at this OLR and at a
      temperature of 57 degrees C with satisfactory COD removal and biogas production.
      The PCR-based DGGE analysis suggested that the thermophilic temperature of 57
      degrees C was suitable for a number of hydrolytic, acidogenic, and acetogenic
      bacteria.

PMID- 22876481
TI  - Analysis of organic nitrogen removal in municipal wastewater by reverse osmosis.
AB  - The results of a pilot study that was conducted to determine the total nitrogen
      removal by the reverse osmosis process are presented. The organic nitrogen
      removal rates are compared with removals observed from three full-scale reverse
      osmosis facilities and four pilot studies. The results of this analysis suggest
      that organic nitrogen removal is variable and that reverse osmosis may not
      consistently produce total nitrogen levels less than 1.0 mg/L without additional
      treatment. Three hypotheses to explain the variability in organic nitrogen
      removal in the different data sets are presented.

PMID- 22876482
TI  - Effect of pH and coexisting anions on removal of phosphate from aqueous solutions
      by inorganic-based mesostructures.
AB  - This study investigated the effect of pH and the presence of coexisting
      (competitive) anions on the removal of phosphate by titanium mesostructures
      synthesized using do- or hexadecyltrimethylammonium bromide. To address these
      research objectives, experiments were conducted (1) under controlled initial pH
      values (2 to 10); and (2) through injection of nitrate, fluoride, chloride, or
      sulfate anions into a phosphate solution. Based on the experimental results, an
      initial of pH of 2 was found to be optimal for use of titanium mesostructures.
      The presence of fluoride anions in solution significantly decreased the removal
      efficiency of phosphate removal (3.56% at 3.95 mg/g). However, the addition of
      nitrate, chloride, and sulfate anions did not affect phosphate removal.

PMID- 22876484
TI  - Wage scale upward.

PMID- 22876483
TI  - Sorption media for stormwater treatment--a laboratory evaluation of five low-cost
      media for their ability to remove metals and phosphorus from artificial
      stormwater.
AB  - Five sorption materials were studied with a focus on polishing pretreated
      stormwater: crushed limestone, shell-sand, zeolite, and two granulates of
      olivine. These materials are commercially available at comparatively low cost and
      have been subjected to a minimum of modification from their natural states. The
      sorbents were tested for phosphorus, arsenic, cadmium, chromium, copper, nickel,
      lead, and zinc at concentration and conditions relevant for typical stormwater.
      The materials were tested for sorption capacity and kinetics. Desorption was
      tested under neutral and alkaline conditions and in the presence of chloride. For
      most sorbent/sorbate combinations, significant sorption occurred within the first
      minutes of contact between sorbent and sorbate. Treatment to the low microgram
      per liter range could be achieved by contact times of less than 1 hour. The study
      indicated that sorption filters can be designed for long life expectancy at
      comparatively low cost by applying the materials tested.

PMID- 22876485
TI  - The hybrid challenge. Planning for imaging-enabled operating rooms.

PMID- 22876486
TI  - Open for business. Retail influences and impacts on health care.

PMID- 22876487
TI  - Start your engines. Generator reliability is key to maintaining power during
      crises.

PMID- 22876488
TI  - The role of ES in choosing interior materials.

PMID- 22876489
TI  - Building code consensus. Health care's place in the ICC development process.

PMID- 22876490
TI  - A strategy for pathogens. How ES can help drive infection prevention efforts.

PMID- 22876491
TI  - The art of conversation.
AB  - The chair, board and staff are essential contributors to meaningful meeting
      dialogue.

PMID- 22876492
TI  - 10 facts about population health.
AB  - Population health is emerging as the foundation of more coordinated care. Here's
      what trustees need to know.

PMID- 22876493
TI  - Performance-driven giving.
AB  - Holding leaders accountable for service excellence can boost charitable
      donations.

PMID- 22876494
TI  - Assessing the 'fit': using competencies to select new board members.

PMID- 22876495
TI  - The mental health crisis.
AB  - As public funding drops and need soars, hospitals are working with other
      providers to find solutions to this problem.

PMID- 22876496
TI  - A plan for smarter spending.
AB  - Four key questions can help the board drive truly effective capital planning for
      medical technology.

PMID- 22876497
TI  - The DuPont way.
AB  - A major manufacturer's safety system has the potential to reduce patient harm.

PMID- 22876498
TI  - Building a lasting impression.
AB  - Organizational culture and values can impact every aspect of hospital operations.

PMID- 22876500
TI  - Turn questions into invitations.

PMID- 22876499
TI  - 38% growth in IT operating budgets since 2007.
AB  - Hospitals are beefing up their IT operating budgets.

PMID- 22876501
TI  - Metrics initiative to boost mental health care.

PMID- 22876502
TI  - The value of dissent.

PMID- 22876503
TI  - Triangulating data to improve care.
AB  - This article explores how Heart of England NHS Foundation Trust has increased its
      capacity to provide credible data to show how care is delivered. The trust
      developed its own evaluation methods using the triangulation process, which
      measures the same outcomes through different methods or sources and compares the
      results to see if they offer the same or similar conclusions. See also case study
      on page 20.

PMID- 22876504
TI  - Triangulating data to improve care: case study.
AB  - The implementation of neonatal nursing indicators focusing on standards of record
      keeping and the core neonatal nursing activities initially failed to bring good
      results. The decision to take an action-planning approach, a cyclical method of
      identifying problems and seeking ways to resolve them, gave staff 'ownership' of
      the process and resulted in rapid progress. The challenge now is to sustain and
      continue improvements in care. This article can be read in conjunction with the
      feature on page 14.

PMID- 22876505
TI  - Developing the RCN Executive Nurse Network.
AB  - The Royal College of Nursing (RCN) has been reviewing how it engages with senior
      nurses across the UK. As part of a new approach to engagement, it was decided to
      establish a UK-wide network for nurses at executive level across all sectors of
      care provision. In this article, the author, who was appointed RCN Executive
      Nurse Network manager in November 2011, explains who the network is for, what it
      offers, how it will work and how it will be developed over the coming year.

PMID- 22876506
TI  - Nursing in the world's war zones.
AB  - This article describes the difficult decisions faced by healthcare workers
      providing treatment in conflict areas to civilians as well as combatants. While
      endeavouring to provide the best possible care including, where practicable,
      follow-up treatment, they daily face the risk of kidnap, attack, takeover of
      hospital facilities, the seizure of drugs and medical equipment, as well as
      having to negotiate checkpoints. Care is provided in conflict zones by charities
      and military medical facilities.

PMID- 22876507
TI  - Redesigning the response to patients with trauma.
AB  - In 2008, a multidisciplinary team of nurses, doctors, clerical staff, a social
      worker and paramedic at Westmead Hospital, Sydney, New South Wales, began a
      project to redesign the composition and practice of the hospital's trauma team.
      This article describes the process involved and explains why staff collaboration,
      the involvement of stakeholders and the sponsorship of the hospital executive
      team were crucial to the success of the project. These principles can be
      transferred to other hospitals.

PMID- 22876508
TI  - Alpha Omega Alpha Honor Medical Society: 1902-2012--celebrating 110 years.

PMID- 22876509
TI  - Anton Chekhov in medical school--and after.

PMID- 22876510
TI  - The heart of Oz. L. Frank Baum's cardiac disease.

PMID- 22876511
TI  - From Auschwitz with love.

PMID- 22876512
TI  - The children of physicians.

PMID- 22876513
TI  - Needlepoint.

PMID- 22876514
TI  - Past, present, and future.

PMID- 22876515
TI  - Standing on the shoulders of giants--Isaac Newton? Bernard of Chartres? Priscian!

PMID- 22876516
TI  - Re: Mentoring and coaching in medicine.

PMID- 22876517
TI  - ICD-10 delay--it's not all bad.

PMID- 22876518
TI  - The closed formulary makes a comeback.

PMID- 22876519
TI  - Case studies that flunk every plausibility test known to mankind.

PMID- 22876520
TI  - The advantage of progress-based incentives.

PMID- 22876521
TI  - Is home infusion ready for prime time?

PMID- 22876522
TI  - Hemoglobin A1c outcomes and health care resource use in type 2 diabetes mellitus
      patients treated with combination oral antidiabetic drugs through step therapy
      and loose-dose and fixed-dose combinations.
AB  - PURPOSE: To compare outcomes of type 2 diabetes mellitus (T2DM) patients
      initiating therapy with FDC vs. those with loose-dose combination (LDC) or step
      therapy (ST) in a managed care population. DESIGN: A retrospective claims
      database analysis. METHODOLOGY: Treatment-naive T2DM patients who were
      continuously enrolled in a health plan during 2006-2009 were studied. Eligible
      patients were assigned to FDC, LDC, or ST cohorts. Glycated hemoglobin goal
      attainment (HbA1c < 7%) was assessed using the American Diabetes Association
      (ADA) treatment guidelines. Health care resources use and costs, including
      inpatient, emergency room (ER), and ambulatoryvisits, were measured during the 12
      months after therapy initiation. All-cause and diabetes-related use and costs
      were assessed. PRINCIPAL FINDINGS: 21,048 patients met study criteria (FDC n =
      8,416, ST n = 8,407, LDC n = 4,225), and 1,926 of these patients had HbA1c
      results. FDC patients had lower rates of post-index all-cause inpatient stays and
      ER visits compared with the other cohorts. FDC patients had lower average counts
      of diabetes-related ambulatory visits (2.7) compared with ST (3.7; p < 0.001) and
      LDC (3.2; p < 0.001) and significantly lower average post-index all-cause and
      diabetes-related costs compared with the other cohorts, with average all-cause
      costs for FDC, ST, and LDC of $8,445, $10,515, and $9,688, respectively, and
      diabe-tes-related costs of $1,641, $2,099, and $1,900, respectively. FDC patients
      had higher rates of achieving HbA1c goal (61%) compared to ST (48%; p < 0.001) or
      LDC (52%; p = 0.015). Differences in outcomes remained following multivariate
      analyses. CONCLUSION: Treatment with FDC was associated with lower health care
      resources use and costs and better likelihood of HbA1c goal attainment.

PMID- 22876523
TI  - Tufts offers its workers short commute to care.

PMID- 22876524
TI  - Left-ventricular-assist device allows remote monitoring using Internet.

PMID- 22876525
TI  - Of mind and matter: psychological dimensions in obesity.
AB  - Obesity is a physiological energy imbalance, a chronic disorder that results from
      an increase in caloric intake and/or a decrease in caloric expenditure. Other
      than the accumulation of excess adipose tissue, there are no signs or symptoms
      characteristic of all obese people. Obesity rates have increased exponentially
      worldwide in the past thirty years for reasons that we do not entirely
      understand. Multiple environmental, genetic, neuro-endocrinological, and
      psychosocial factors contribute to the development of obesity. Though there are
      many different, and even controversial, frameworks for obesity, most researchers
      acknowledge that it can lead to serious medical and psychological morbidity. This
      paper focuses on psychological dimensions in the study of obesity: the intricate
      human "minded brain" that promotes self-regulation, motivation, and self
      efficacy; the complexities involved in considering obesity a psychiatric
      disorder, with the possibility of a so-called "obese personality"; the role of
      stigma, prejudice, and discrimination; and psychiatric symptomatology among the
      obese.

PMID- 22876526
TI  - Pleasure seeking and the aspect of longing for an object in perversion. A
      neuropsychoanalytical perspective.
AB  - In modern psychiatric classifications the term paraphilia has replaced the term
      perversion by changing the scope of the definitions from avoided procreation to
      failures of relationship-aspects of sexuality. Contemporary psychoanalysts also
      seem less interested in pleasure seeking aspects, which were so important within
      original Freudian thought, and instead concentrate interpretation on hostility
      and the history of the representation of objects. This paper discusses the
      connection between distinct object representations in perversions and attachment
      theory and neurobiological representations. It will discuss the observation that
      the neglect of pleasure seeking in perversion often results in a failure to
      recognise the addiction-like aspects of perversion, which seem to be particularly
      relevant to modern psychiatric and psychological thinking. The SEEKING-system
      (Panksepp, 1998) is used to conceptualise a neurobiological basis for pleasure
      seeking. This SEEKING-system may be "hijacked" by rewards in different forms of
      addiction as well as in sexual obsessions. The polarity between "drive
      representation" and "object representation," as created by Freud (1933, 1940a),
      may correspond to the polarity identified in contemporary thinking between the
      addictive or compulsive characteristics of sexual gratification (drive
      representation) and the influence of early object representation on the later
      ability to integrate instinctual wishes into relationships (object
      representation).

PMID- 22876527
TI  - The psychodynamics of transference--a virtual reality model.
AB  - OBJECTIVE: Virtual reality is not only being utilized increasingly as an
      enhancement for diagnosis and treatment of psychiatric illness, but it also can
      be used to model theories, generate hypotheses, and provide a new context for
      teaching psychodynamic therapy. Here we describe the use of an online virtual
      world--Second Life--as a heuristic tool for understanding and teaching a key
      psychoanalytic concept, transference. METHODS: Using an extended vignette to
      illustrate the results of the modeling process, we explore teaching the
      vicissitudes of object relationships by means of analogs in virtual reality.
      RESULTS: Simple reframing operations demonstrate how traditional dynamic theories
      of psychiatric treatment can be brought to life in simulations using modern
      computer technology. CONCLUSIONS: Virtual worlds offer a helpful analogy in
      teaching complex psychoanalytic concepts, such as transference.

PMID- 22876528
TI  - Three cases of dissociative identity disorder and co-occurring borderline
      personality disorder treated with dynamic deconstructive psychotherapy.
AB  - Dissociative Identity Disorder (DID) is an under-researched entity and there are
      no clinical trials employing manual-based therapies and validated outcome
      measures. There is evidence that borderline personality disorder (BPD) commonly
      co-occurs with DID and can worsen its course. The authors report three cases of
      DID with co-occurring BPD that we successfully treated with a manual-based
      treatment, Dynamic Deconstructive Psychotherapy (DDP). Each of the three clients
      achieved a 34% to 79% reduction in their Dissociative Experiences Scale scores
      within 12 months of initiating therapy. Dynamic Deconstructive Psychotherapy was
      developed for treatment refractory BPD and differs in some respects from expert
      consensus treatment of DID. It may be a promising modality for DID complicated by
      co-occurring BPD.

PMID- 22876529
TI  - Psychodynamic therapy for depression in women with infants and young children.
AB  - BACKGROUND: It has long been known that the rate of depression is high among
      women with infants and young children. In recent research a psychodynamic therapy
      group was found to be beneficial for a self-selected, postnatal subgroup of women
      who were of middle socio-economic status (SES), educated and who met DSM-IV
      criteria for clinical or subclinical depression. The current study sought to
      replicate these findings with individual psychodynamic therapy and to compare
      outcomes for three psychodynamic treatment conditions: individual, group, and
      combined individual and group. METHOD: Patients began and left treatment from
      each of the three psychodynamic therapy conditions on a self-determined basis.
      Pre- and postintervention DSM-IV Global Assessment of Functioning (GAF) were
      obtained by reliable blind raters. A ten-variable, self-administered
      postintervention outcome questionnaire provided further data. RESULTS: Women (n =
      58) in all three therapeutic conditions showed statistically significant
      improvement in their pre-to-post GAF and large treatment effects. On the
      questionnaire, they indicated that they were affected positively by all three
      conditions. Statistically significant differences among treatment conditions
      favored the individual treatment. CONCLUSIONS: Psychodynamic therapy appears well
      suited for the population of women in this study, especially when administered on
      an individual basis. The model employed here emphasized receiving and developing
      empathic emotional attunement, insight into one's relationships and early
      experiences, and a process for expressing feelings and resolving problems.
      Compared to group and combination therapies, the individual treatment may afford
      the greatest opportunity for receiving and developing these features and, thus,
      the best outcomes.

PMID- 22876530
TI  - Growth failure in children with cystic fibrosis.
AB  - Poor linear growth and inadequate weight gain are very common problems in cystic
      fibrosis (CF) children. The most important factors involved in growth failure are
      undernutrition or malnutrition, chronic inflammation, lung disease, and
      corticosteroid treatment. Nutritional support and pharmacological therapy with
      recombinant human growth hormone are essential for a good management of children
      with CF, although these children are shorter and lighter than healthy children,
      and despite the catch-up growth observed after diagnosis, deficit in
      length/height and weight continues to be seen until adulthood. Early diagnosis is
      essential to ensure better nutritional status and growth, potentially associated
      with better respiratory function and prognosis. The aims of this review are try
      to explain etiology and pathogenetic mechanisms of growth failure in CF children
      and clarify their role in the disease morbidity and in clinical outcome,
      especially in relation to progressive decline of pulmonary function.

PMID- 22876531
TI  - Approach to the management of slipped capital femoral epiphysis and primary
      hyperparathyroidism.
AB  - CONTEXT: Worldwide, only nine cases of revealing slipped capital femoral
      epiphysis (SCFE) associated with primary hyperparathyroidism (PHP) have been
      reported. CASE ILLUSTRATION: This study included adolescent subjects with the
      described association, the clinical course, and exhibiting the leading
      pathogeneses. METHODS: Here, we reviewed all known cases and developed an
      effective approach to the management of SCFE and PHP. RESULTS: In cases of
      emergency, SCFE fixation is primarily done regardless of any preexistent
      hypercalcemia due to PHP and followed by parathyroidectomy as soon as possible.
      In cases of mild and moderate hypercalcemia, whether SCFE fixation is followed by
      parathyroidectomy and vice versa or resolved during a single operating session
      depends on manifest side effects due to hyercalcemia. Patients with severe
      hypercalcema should undergo urgent parathyroidectomy, followed by immediate
      orthopedic surgery, even as a simultaneous procedure. This is to avoid onset of
      hypercalcemic side effects or worsening of preexisting side manifestations
      resulting from hypercalcemia. CONCLUSION: Our report demonstrates that SCFE
      presenting with hypercalcemia, with signs of low bone density, or in atypical age
      deserves further workup for secondary causes. In addition, the newly developed
      systematic approach toward achieving an effective, efficient management should
      help to improve the patients' long-term outcome.

PMID- 22876532
TI  - Thyroid developmental anomalies among first-degree relatives of children with
      thyroid dysgenesis and congenital hypothyroidism.
AB  - BACKGROUND: Thyroid dysgenesis (TD) is usually sporadic. In approximately 2%-8%
      of TD cases, familial TD has been identified. AIMS: The aim of this study is to
      define the prevalence of thyroid developmental anomalies in first-degree
      relatives of children with TD-caused congenital hypothyroidism (CH). METHODS: The
      investigation included 102 relatives of 33 children with CH and TD (study group)
      and 27 relatives of 12 normal children (comparative group). All the individuals
      were subjected to thyroid ultrasound and serum thyroid stimulating hormone (TSH)
      and free T4 (FT4) determinations. Statistical analysis was based on Fisher's
      exact test. RESULTS: TD-caused familial CH was noted in 2 of 33 (6%) children
      with CH. Asymptomatic thyroid developmental anomaly was seen in 1 of 102 (1%)
      relatives - left thyroid lobe hypoplasia in the mother of a girl with CH and
      thyroid severe hypoplasia. Familial prevalence of asymptomatic TD in the study
      group was observed in 1 of 32 families (3.13%). None of the comparative group
      members demonstrated any thyroid developmental anomalies. CONCLUSIONS: The
      prevalence rate of thyroid developmental anomalies in the study group is slightly
      higher than in the comparative group. These disturbances are asymptomatic.

PMID- 22876533
TI  - TSHR is the main causative locus in autosomal recessively inherited thyroid
      dysgenesis.
AB  - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and
      results in mental retardation if untreated. Eighty-five percent of CH cases are
      due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2%
      of thyroid dysgenesis is familial, indicating the involvement of genetic factors
      in the aetiology of the disease. In this study, we aimed to investigate the
      Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital
      hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report
      the results of the second part (n=105) of our large cohort (n=244), representing
      the largest such cohort in the literature, and interpret the overall results of
      the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400
      unaffected control subjects were included in the study. In familial cases, first,
      we performed potential linkage analysis of four known genes causing CHNG (TSHR,
      PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the
      presence of mutations in these genes by direct sequencing. In addition, in silico
      analyses of the predicted structural effects of TSHR mutations were performed and
      related to the mutation specific disease phenotype. We detected eight new TSHR
      mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the
      biallelic TSHR mutations detected in familial cases were present in the cohort of
      50 sporadic cases. Genotype/phenotype relationships were established between TSHR
      mutations and resulting clinical presentations. Here we conclude that TSHR
      mutations are the main detectable cause of autosomal recessively inherited
      thyroid dysgenesis. We also outline a new genetic testing strategy for the
      investigation of suspected autosomal recessive non-goitrous CH.

PMID- 22876534
TI  - When to operate on ovarian cysts in children?
AB  - BACKGROUND: Ovarian cysts are rare conditions in the pediatric age group. They
      are characterized by different clinical presentations and by the need to
      establish adequate type and timing of treatment in order to prevent
      complications, such as ovarian necrosis after torsion and infertility. The
      diagnostic approach should differentiate benign occasional findings, such as
      follicular cysts, from neoplastic lesions, and functional cysts which can occur
      either isolated or in the context of McCune-Albright syndrome. Our aim was to
      review all the patients affected by ovarian pathologies seen in our department in
      the past 5 years, in order to establish a protocol for the correct management of
      these conditions. METHODS: In the past 5 years we studied 133 patients diagnosed
      with ovarian lesion. We subdivided the patients into three groups according to
      age: group A (age <6 months: 66 cases); group B (pre-pubertal patients, age 7
      months to 10 years: 10 cases); and group C (pubertal patients, age 11-14 years:
      57 cases). We collected historical and clinical data and assigned specific cut
      off values in order to perform statistical analysis (Fisher's exact test)
      comparing the three groups. RESULTS: Ultrasound examination proved to be
      indispensable in the early detection of ovarian lesions and for identifying the
      correct treatment. Cyst size, and moreover appearance with ultrasound, were
      important considerations when selecting the most appropriate therapeutic
      approach. The larger lesions were found in group B, giving symptoms that required
      hospitalization (pelvic pain, nausea and vomiting) and leading to increased
      incidence of postoperative complications. Laparoscopic surgery appeared to be
      safe and effective for the treatment of ovarian pathologies. CONCLUSION: The
      management of ovarian lesions in children must be based on a minimally invasive
      approach, based on the patient's age and ultrasound findings. Treatment should be
      conservative, with ovariectomy undertaken only when essential. In adolescents,
      only cysts larger than 6 cm that do not resolve with estro-progestinic therapy
      within 6 months should be surgically approached; in infants, any signs of cyst
      complications must be addressed surgically.

PMID- 22876535
TI  - Partial anomalous pulmonary venous return is common in Turner syndrome.
AB  - BACKGROUND: Cardiovascular disease affects >50% of Turner syndrome (TS) patients.
      With newer imaging modalities, this prevalence increases and the spectrum of
      recognized anomalies broadens. OBJECTIVE: To determine the prevalence and
      hemodynamic significance of partial anomalous pulmonary venous return (PAPVR) in
      adolescents and young adults with TS using transthoracic echocardiogram (TTE) and
      cardiac magnetic resonance (CMR), and to study the association with phenotype.
      METHODS: The records of 39 young TS patients who had received TTE and CMR were
      reviewed. RESULTS: PAPVR was diagnosed in seven (18%) patients; six were newly
      diagnosed by CMR after normal TTE. In one subject, PAPVR was associated with
      right ventricular enlargement and a pulmonic blood flow (Qp) to systemic blood
      flow (Qs) ratio of 1.9:1.0, necessitating surgical repair. In other subjects with
      and without PAPVR, Qp:Qs and the right ventricle to left ventricle end-diastolic
      volume ratio were statistically different. Other clinical features were not
      predictive of PAPVR. CONCLUSIONS: The prevalence of PAPVR is high in TS, and it
      may be hemodynamically significant. Diagnosis by TTE can be difficult.
      Appropriate screening and management are indicated.

PMID- 22876536
TI  - Uterine development in patients with Turner syndrome: relation to hormone
      replacement therapy and karyotype.
AB  - Our study aimed to assess uterine development in Turner syndrome patients and its
      relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound
      was used to assess uterine size and shape, and ovarian volume in 40 Turner
      syndrome patients. Information on hormone replacement therapy was collected from
      patients' notes. Among the 40 patients studied, 57.5% started estrogen therapy
      and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5%
      had fully mature uterus and 17.5% had transitional uterus. Uterine volume was
      associated with age (p < 0.001), height (p = 0.002), weight (p = 0.001), years of
      estrogen use (p < 0.001), estrogen dose (p = 0.016), current estrogen use ( p
      =0.001) and Tanner breast stage ( p <0.001). Uterine volume was not affected by
      the type of estrogen used ( p =0.40) and karyotype ( p =0.40). Patients with
      Turner syndrome treated with estrogen (of adequate dose and duration) may attain
      a normal, mature uterine size and configuration, even at a late start of hormone
      replacement therapy and regardless of karyotype.

PMID- 22876537
TI  - Ovarian and uterine ultrasonography and relation to puberty in healthy girls
      between 6 and 16 years in the Turkish population: a cross-sectional study.
AB  - AIM: To investigate uterine and ovarian ultrasonography in healthy girls and
      establish reliable cut-off limits in the Turkish population. METHODS: The study
      was performed on 90 girls between 6 and 16 years of age with bone age, hormonal
      evaluation and pelvic ultrasounds. Total uterine length (TUL), anteroposterior
      diameters of corpus (COAP), anteroposterior diameters of cervix (CEAP),
      fundus/cervix ratio (F/C), uterine volume (UV), ovarian volume (OV) and
      morphology were obtained. The data were stratified according to various pubertal
      stages and ages. RESULTS: Age-related increases of pelvic organs were noted after
      10-10.9 years. Significant correlation was detectable between age and OV, TUL and
      UV in pubertal girls, but age only correlated with OV in prepubertal girls. A cut
      off value of 4 cm for TUL, 2.57 cm(3) for UV and 1.58 cm(3) for OV were the best
      discrimination values for entering puberty. CONCLUSION: The data herein may be
      useful in screening cases around puberty when continuous changes take place.

PMID- 22876538
TI  - Assessment of gonadal function in boys and adolescents at the diagnosis of
      neoplastic disease.
AB  - OBJECTIVE: We assessed the gonadal function in boys with a newly diagnosed
      neoplastic disease prior to chemotherapy. Eighty-four boys (48 prepubertal and 36
      pubertal) were evaluated, including 50 with acute lymphoblastic leukemia (ALL) or
      non-Hodgkin lymphoma (NHL), 10 with Hodgkin lymphoma (HL), and 24 with solid
      tumors. The control group consisted of 24 healthy prepubertal and 24 pubertal
      boys. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      inhibin B, and testosterone were determined, and testicular volumes were
      measured. RESULTS: Patients in prepuberty and early puberty (Tanner stages 1-3)
      diagnosed with ALL/NHL or solid tumor presented normal serum reproductive hormone
      levels, whereas in ALL/NHL patients in Tanner stages 4-5, the mean values of
      inhibin B were significantly lower (45.18 +/- 33.85 vs. 153.57 +/- 71.44 ng/L, p
      = 0.0027). In patients with HL in Tanner stages 4-5, a statistically significant
      lower mean inhibin B level (100.44 +/- 67.45 versus 153.57 +/-71.44 ng/L, p =
      0.0027), higher mean FSH level (6.3 +/- 3.6 versus 4.6 +/- 2.2 mIU/mL, p = 0.05),
      and higher mean LH level (5.9 +/- 4.0 versus 3.6 +/- 1.8 mIU/mL, p = 0.05) were
      observed. No statistically significant differences were noted in assessed
      hormones in patients with solid tumors, independently of Tanner stage.
      CONCLUSION: Our analysis indicates that adolescents with ALL/NHL and HL prior to
      treatment, exhibit reduced levels of inhibin B, which indirectly suggests the
      possibility of spermatogenesis dysfunction.

PMID- 22876539
TI  - Environmental and genetic factors influence age at menarche in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: We hypothesized that body mass index (BMI) and DNA variants would
      predict age at menarche in polycystic ovarian syndrome (PCOS). SUBJECTS: Subjects
      aged 18-45 years with PCOS defined by the National Institutes of Health criteria
      (n=522) and controls with regular menstrual cycles and no hyperandrogenism
      (n=472) were studied. METHODS: Age at menarche was compared between PCOS cases
      and controls and examined as a function of multiple parameters. RESULTS: There
      was a strong inverse relationship between BMI and age at menarche in PCOS (r=
      0.32, p=5 x lO(-11)). The chromosome 6 rs7759938-T variant was associated with
      earlier age at menarche in women with PCOS (12.60 +/- 0.09 vs. 13.41 +/- 0.23
      years; genotype TT vs. CC; p = 0.006). Age at menarche was predicted by PCOS
      status (beta = 0.512, p < 0.001), reported weight group at 10-14 years (beta = 
      0.432, p < 0.001), current BMI (beta = -0.0202, p = 0.01), and genotype (beta =
      0.169, p = 0.02). CONCLUSIONS: Age at menarche in women with PCOS is influenced
      by BMI and genetic variants near LIN28B.

PMID- 22876541
TI  - Non-invasive measurement of adrenal response after standardized exercise tests in
      prepubertal children.
AB  - OBJECTIVE: To determine the feasibility of non-invasive evaluation of adrenal
      response in healthy prepubertal children by standardized exercise tests. METHODS:
      On separate occasions, healthy prepubertal children performed a submaximal
      cycling test, a maximal cycling test, and a 20-m shuttle-run test. Salivary
      cortisol levels were determined before exercise, and 1 and 15 min after exercise.
      RESULTS: Immediately after cessation of the cycling and shuttle-run tests,
      salivary cortisol levels remained unchanged or decreased. Fifteen minutes after
      the shuttle-run test, salivary cortisol levels increased significantly. This
      increase in salivary cortisol levels was not observed 15 min after the cessation
      of the cycling tests. CONCLUSION: The results of this study demonstrate a
      different response in salivary cortisol levels after standardized cycling and
      running tests in prepubertal children. The increase in salivary cortisol levels
      found after a short standardized running test suggests that this may be a
      practical non-invasive method for evaluating adrenal response in healthy
      prepubertal children.

PMID- 22876540
TI  - Vitamin D status in children with Hashimoto thyroiditis.
AB  - OBJECTIVE: To investigate vitamin D status in children with Hashimoto
      thyroiditis. SUBJECTS AND METHODS: The study group consisted of 78 children
      recently diagnosed as Hashimoto thyroiditis and 74 subjects as the control group.
      Parameters of calcium metabolism, thyroid function tests, and 25-hydroxyvitamin D
      [25(OH)D] levels were measured. RESULTS: Vitamin D deficiency rate was
      significantly higher in the Hashimoto group compared with the control subjects
      (73.1% vs. 17.6%, p < 0.0001). In the Hashimoto group, mean 25(OH)D levels were
      significantly lower compared with the control group (31.2 +/- 11.5 versus 57.9 +/
      19.7 nmol/L, p < 0.001) and was inversely correlated with the anti-thyroid
      peroxidase (anti-TPO) levels (r = -0.30, p = 0.007). CONCLUSION: The higher
      vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group
      together with the inverse correlation between vitamin D and anti-TPO suggest that
      vitamin D deficiency may have a role in the autoimmune process in Hashimoto
      thyroiditis in children.

PMID- 22876542
TI  - Bone metabolism biomarkers, body weight, and bone age in healthy Brazilian male
      adolescents.
AB  - Eighty-seven male volunteers were grouped according to bone age (BA): 10-12 years
      (n=25), 13-15 years (n=36), and 16-18 years (n=26), and the following were
      recorded for each: weight (kg), height (m), BMI (kg/m(2)), calcium intake from
      three 24-h food recalls (mg/day), puberty evaluation by Tanner stages, bone
      biomarker (BB) evaluation, serum osteocalcin (OC), bone alkaline phosphatase
      (BAP), carboxyterminal telopeptide (S-CTx), and bone mineral density (BMD)
      evaluations by dual-energy X-ray absorptiometry (g x cm(2)) in the lumbar spine,
      proximal femur, and the whole body. BBs showed similar behaviors, and very high
      median values were observed for individuals aged 13-15 years (BAP = 155.50 IU/L,
      OC = 41.63 ng/mL, S-CT x =2.09 ng/mL). Lower median BB values were observed with
      advancing BA between 16 and 18 years (BA P =79.80 IU/L, O C =27.80 ng/mL, S-CT x
      =1.65 ng/mL). Stepwise multiple regression analysis showed body weight associated
      with BA as independent variables with greater determination power for S-CTx (r(2)
      = 0.40) and OC (r(2)=0.21). For BAP, stepwise analysis showed body weight and
      whole-body BMD (r(2) = 0.34). All predictive models showed significance ( p <
      0.01). A high turnover for both bone formation and resorption biomarkers,
      particularly from 13 to 15 years of BA, were observed along with very low values
      in the 16-18 age range. Weight and BA were significant in determining predictive
      equations of OC and of S-CTx, whereas for BAP, weight and BMD of full body were
      selected.

PMID- 22876543
TI  - Safety and efficacy of a 1-year treatment with zoledronic acid compared with
      pamidronate in children with osteogenesis imperfecta.
AB  - Pamidronate (PAM) infusion is the standard treatment in children with
      osteogenesis imperfecta (OI). Zoledronic acid (ZOL) is a bisphosphonate with
      higher potency and faster intravenous infusion, but its efficacy and safety has
      not been established for OI patients. We report an open-label, prospective, and
      randomized clinical analysis to study the safety and efficacy of ZOL compared
      with PAM in 23 children with OI. They were selected to receive PAM (PAM group), 1
      mg/kg/day, over 2 days or ZOL (ZOL group), 0.025-0.05 mg/kg/day, over 2 days
      every 3-4 months according to their ages, during a 1-year follow-up. They were
      observed for clinical and biochemical parameters, side effects, bone mineral
      density (BMD), and fracture rate. After treatment, the PAM and ZOL groups average
      lumbar spine (LS) BMD increased by 51.8% (p = 0.053) and 67.6% (p = 0.003),
      respectively. Parallel improvement was seen in LS Z-score in the PAM and ZOL
      groups, with scores of -5.3 to -3.8 (p = 0.032) and -4.8 to -2.3 (p = 0.007),
      respectively. LS Z-score for the ZOL group at the end of treatment was higher
      compared with the PAM group but only a borderline significance (p = 0.053). The
      total alkaline phosphatase (AP) in the ZOL group significantly decreased from
      baseline at third and fourth infusion (p = 0.032). Mild side effects were similar
      in both groups, but no severe clinical symptoms were reported. In conclusion, the
      present study shows that the use of ZOL in the dosage and period studied was safe
      and efficient to promote a clinical and densitometric improvement, similarly to
      PAM. Further studies are needed to establish optimal dosing and long-term safety.

PMID- 22876544
TI  - Evaluation and comparison of safety, convenience and cost of administering
      intravenous pamidronate infusions to children in the home and ambulatory care
      settings.
AB  - The use of bisphosphonates in children to treat low bone mineral density has
      increased. Safety and efficacy of pamidronate has been previously demonstrated.
      However, little research has been done on pamidronate infusion in the home health
      setting for patients with metabolic bone disease. Data were collected via a
      survey to assess satisfaction and convenience of infusions. Adverse events were
      measured by collecting calcium levels before and after infusions. Infusion costs
      were estimated from the standard orders from one home health agency and our
      infusion center. We found no difference in the rates of hypocalcemia between the
      two groups. The survey results showed high satisfaction for both groups, with
      higher scores in the home health group for convenience and stress. Home health
      infusions showed lower cost and less absenteeism from school and work. Home
      health-based pamidronate infusion appears to be safe, less expensive, and is
      associated with high patient satisfaction.

PMID- 22876545
TI  - Clinical profile and etiologies of children with central diabetes insipidus: a
      single-center experience from Turkey.
AB  - AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal,
      and radiological characteristics of children with central diabetes insipidus
      (DI). METHODS: Case records of 34 children (22 boys and 12 girls) with documented
      central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz
      Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was
      6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior
      pituitary function assessment and magnetic resonance imaging of pituitary at
      diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS: The
      etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%)
      patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of
      craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients,
      germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1
      patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and
      autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone
      deficiencies were documented in 18 (53%) patients. Organic central DI group had a
      greater prevalence of anterior pituitary hormone deficiency when compared with
      the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of
      patients with organic etiology were significantly lower than the idiopathic group
      (155 and 178, cm respectively; p = 0.021). CONCLUSIONS: Etiological diagnosis is
      possible in a significant proportion (70.6%) of children with central DI.
      Findings of this study suggest that accompanying anterior pituitary hormone
      deficiencies and short stature may be considered as indicators of organic
      etiology.

PMID- 22876546
TI  - Audiologic evaluation in pediatric patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: The aim of this study was to perform audiological evaluation of
      children with type 1 diabetes mellitus (DM). METHODS: One hundred DM patients
      (200 ears) were included in the study. Pure-tone audiometry at frequencies of
      0.25, 0.5, 1, 2, 4, and 8 kHz; immittance measures including tympanometry and
      acoustic reflex testing; transient evoked otoacoustic emission (TEOAE); and
      auditory brainstem response (ABR) testing were performed in the patients. The
      results were statistically compared with metabolic control of DM, positive and
      negative autoantibodies, duration of DM, and present concomitant Hashimoto and
      celiac diseases. RESULTS: The proportion with a result of 'fail' for the TEOAE
      test in the DM patients was not statistically significant among all groups (p >
      0.05). The autoantibodies, blood glucose level, and present concomitant Hashimoto
      and celiac diseases were not associated with prolonged ABR latencies. However,
      ABR peripheral transmission time (wave I) was significantly delayed with the
      increasing duration of DM (p < 0.05). CONCLUSION: Pediatric patients with type 1
      DM do not frequently present with cochleovestibular symptoms, but show higher
      audiometric thresholds and the absence of or reduction in TEOAE amplitudes. In
      ABR testing, the increase in the peripheral transmission time (wave I) is more
      suggestive of retrocochlear alterations in pediatric cases of type 1 DM compared
      with conventional audiometric tests (e.g., pure-tone audiometry and OAEs), which
      may indicate possible initial auditory neuropathy. Further longitudinal
      investigations on a wide range of control and pediatric subjects with DM will be
      necessary to confirm the present data and to detect initial auditory neuropathy.

PMID- 22876548
TI  - Evaluation of neutrophil gelatinase-associated lipocalin in normoalbuminuric
      normotensive type 1 diabetic adolescents.
AB  - AIMS: The aims of this study were to determine neutrophil gelatinase-associated
      lipocalin (NGAL) levels in normoalbuminuric and normotensive adolescents with
      type 1 diabetes and to assess the relationship between NGAL and clinical and
      laboratory variables. METHODS: Forty-six adolescents with type 1 diabetes [male/
      female (M/F) ratio, 24/22; median age, 14.5 years; range, 12.2-16 years; diabetes
      duration, 4.8 years; range, 2.6-6.7 years; hemoglobin A1c (HbA1c), 7.9%; range,
      7.2%-9.2%] and 21 healthy controls (M/F, 7/14; median age, 14.8 years; range,
      13.6-15.5 years) were compared regarding clinical, laboratory, and ambulatory
      blood pressure monitoring variables. RESULTS: Median blood and urine glucose,
      HbA1c, urine NGAL/creatinine ratio [13.2 (range, 8.3-43.1) vs. 4.8 (range, 2.9
      20.2), p = 0.015], and daytime systolic and diastolic blood pressure (BP)
      standard deviation score and BP loads were found higher in diabetic adolescents.
      Urine NGAL levels were found to be correlated with albumin/creatinine ratio (r =
      0.452, p = 0.002), whereas plasma NGAL levels were correlated with nighttime
      systolic BP load (r = 0.309, p = 0.037). Patients with high-normal albuminuria
      (n=6) had higher urine NGAL levels [48.7 ng/mL (range, 27.9-149.1 ng/mL) vs. 14.3
      ng/mL (range, 3.5-41 ng/mL), p = 0.014] and urine NGAL/creatinine ratio [39.3
      ng/mg (range, 21.1-126.3 ng/mg) vs. 11.8 ng/mg (range, 6.3-40.9 ng/mg), p = 0.03]
      compared with those of controls and higher urine NGAL levels compared with that
      of diabetic adolescents with low-normal albuminuria [n=40, 11.2 ng/mL (range, 6
      23.4 ng/mL), p = 0.004]. CONCLUSIONS: Normoalbuminuric and normotensive
      adolescents with type 1 diabetes have elevated urinary NGAL values, which might
      indicate kidney injury.

PMID- 22876547
TI  - An after-school dance and lifestyle education program reduces risk factors for
      heart disease and diabetes in elementary school children.
AB  - BACKGROUND: Forty-three percent of New York City's (NYC) school-age children are
      overweight or obese, placing them at risk for heart disease and type 2 diabetes
      mellitus (T2DM). OBJECTIVE: The objective of this study was to determine if an
      intensive after-school dance and lifestyle education program would reduce risk
      factors for heart disease, T2DM, and improve lifestyle choices. SUBJECTS: Subject
      include 64 fourth- and fifth-grade students at an elementary school in NYC.
      METHODS: Students received freestyle dance and lifestyle classes for 16 weeks and
      were evaluated for changes in body composition, endurance, biochemical
      measurements, and lifestyle choices. RESULTS: Significant improvements in BMI
      percentiles were found among children in the overweight and obese categories as
      well as in endurance and biochemical measurements that reflect heart disease and
      diabetes risk. Improvement was also reported in lifestyle choices. CONCLUSION: An
      intensive after-school dance and lifestyle education program can reduce risk
      factors for heart disease and T2DM and improve lifestyle choices among elementary
      school children.

PMID- 22876549
TI  - The association of serum lipocalin-2 levels with metabolic and clinical
      parameters in obese children: a pilot study.
AB  - OBJECTIVE: We aimed to evaluate the association between serum lipocalin-2 level
      and clinical and metabolic parameters in obese children. METHODS: The study
      included obese children with a body mass index (BMI) >95th percentile who
      presented to Kecioren Teaching and Research Hospital with the complaint of weight
      gain and healthy children with a BMI <85th percentile. The height and weight of
      the patients were measured for compartment of anthropometric data. Fasting blood
      glucose, insulin, lipid profile, and serum lipocalin-2 level were measured to
      evaluate the laboratory parameters. RESULTS: The study included 33 obese and 34
      healthy nonobese children. Comparison of data on the obese subjects with those of
      the healthy subjects shows differences in BMI, BMI-SDS, triglyceride, insulin,
      and homeostasis model assessment index-insulin resistance levels between the two
      groups were statistically significant (p < 0.05), whereas serum lipocalin-2 was
      not statistically significant (p >0.05). There was no statistically significant
      difference in serum lipocalin-2 levels when obese and control groups were
      reclassified as prepubertal and pubertal ( p >0.05). CONCLUSIONS: In this study,
      we did not find any relationships among serum lipocalin-2 level, anthropometric
      parameters, or metabolic parameters. According to the results of this study, we
      do not suggest routine investigation of serum lipocalin-2 level in obese subjects
      for risk stratification of the obesity-related complications.

PMID- 22876550
TI  - Metabolic disorders in vertically HIV-infected children: future adults at risk
      for cardiovascular disease.
AB  - BACKGROUND: Despite metabolic disorders in HIV-infected children being widely
      described, there is still a lack of agreed criteria for diagnoses and management.
      Numerous studies are coming from other settings and results are heterogeneous
      when assessing several analytical and clinical parameters. OBJECTIVES: To
      describe the prevalence of metabolic disorders and associated risk factors in the
      Spanish National cohort of HIV-infected pediatric patients (CoRISpe). METHODS:
      This was a cross-sectional study following all vertically HIV-infected children
      and adolescents in three referral centers included in the CoRISpe. Metabolic data
      (fasting lipids, glucose and insulin levels and thyroid hormone levels) were
      collected. Fat distribution was clinically assessed by expert clinicians.
      RESULTS: We included 157 patients [median age 13 years, interquartile range (IQR)
      10-16]. Median duration of antiretroviral therapy was 10.2 years (IQR 5.0-13.0).
      Almost 20% of patients had insulin resistance and this was associated with
      hepatitis C co-infection, current use of stavudine (d4T) and
      hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia were found in
      23.9% and 24.8% of patients and were associated with current use of protease
      inhibitors (p = 0.042 and p = 0.022, respectively). Abnormal fat distribution was
      observed in 63 patients (40.5%): lipoatrophy in 32 (20.4%), lipohypertrophy in
      eight (5.1%) and a mixed pattern in 23 patients (14.6%), and it was significantly
      associated with previous exposure to stavudine (p < 0.001). CONCLUSIONS:
      Metabolic disorders are a significant problem in our HIV-infected pediatric
      population. We need to encourage the development of global strategies and the
      creation of consensus guidelines that can decrease the cardiovascular risk in
      this population.

PMID- 22876551
TI  - Ghrelin and growth hormone secretagogue receptor (GHSR) genes are not commonly
      involved in growth or weight abnormalities in an Israeli pediatric population.
AB  - CONTEXT AND OBJECTIVE: Ghrelin and its receptor, growth hormone secretagogue
      receptor (GHSR), have key roles in appetite control and growth regulation. To
      date, only few mutations of GHSR have been identified in children with obesity
      and short stature. We hypothesized that mutations in ghrelin or GHSR will result
      in disrupted growth and weight regulation in children. DESIGN: A total of 98
      subjects (38 females and 60 males) were enrolled with failure to thrive (FIT)
      (n=9), GH deficiency (GHD) (n=44), idiopathic short stature (ISS) (n=22) or
      obesity (n=23). The coding exons of both ghrelin and GHSR genes were screened for
      mutations by sequencing. RESULTS: Seven different sequence changes were
      identified in GHSR, two of them novel and five described previously. One
      previously described sequence change (p.L72M) in the ghrelin gene was identified
      in five patients; however, the same variant was identified at a higher rate in
      controls. A high rate of sequence changes was shown in ghrelin and its receptor,
      GHSR, in our population, but none of these changes affected the coding region of
      the protein. CONCLUSIONS: Despite the major role of ghrelin in growth and
      appetite regulation, our results indicate that mutations in ghrelin and GHSR do
      not explain short stature and weight regulation disorders in children in our
      population.

PMID- 22876552
TI  - Splenogonadal fusion and sex reversal.
AB  - Splenogonadal fusion is a rare congenital malformation where an abnormal union
      occurs between the spleen and gonad or mesonephric derivatives. Although it
      occurs in females it is much less prevalent than in males (male:female ratio,
      16:1), but this may partly be because of the inaccessibility of the female gonads
      leading to under-diagnosis. To our knowledge this is the first case of
      splenogonadal fusion associated with sex reversal reported in the literature.

PMID- 22876553
TI  - The earlier described mutation (c.307c > T [p.R103X]) in the SRD5A2 gene causing
      a 46,XY female phenotype.
AB  - Deletions and mutations in the 5-alpha-reductase type 2 (SRD5A2) gene have been
      identified in 46,XY disorders of sexual differentiation (DSD). The clinical
      spectrum is heterogeneous, varying from a normal female external genital
      appearance to clitoromegaly and isolated micropenis or microphallus associated
      with hypospadias of various degrees. We describe a 46,XY DSD patient with a
      homozygous c.307C>T (p.R103X) mutation in the SRD5A2 gene. The case presented
      with a normal female external genital phenotype.

PMID- 22876554
TI  - Sertoli cell tumor and intratubular germ cell neoplasia located in separate
      gonads in an adolescent patient with complete androgen insensitivity: a case
      report and review of literature.
AB  - Complete androgen insensitivity syndrome (AIS) is an X-linked disorder of sex
      development. Surgical management entails timely gonadectomy given the risk of
      malignant transformation. Our patient presented at age 15 years with primary
      amenorrhea. Initial laboratory testing showed elevated testosterone, luteinizing
      hormone, anti-Mullerian hormone levels, and 46,XY karyotype. Imaging studies
      showed no uterus, ovaries, and identified two candidate gonads. She underwent
      bilateral gonadectomy. Pathology reports revealed Sertoli cell and intratubular
      germ cell tumors located in separate gonads. Our case is the first report of the
      youngest patient with AIS with bilateral gonadal tumors derived from different
      histological origins. We also review literature for reports of AIS patients with
      gonadal tumors. Currently, there is no consensus for the timing of gonadectomy in
      AIS patients. However, given the varying potential for malignant transformation
      of gonads in AIS patients with different phenotypes, development of a
      standardized treatment guideline is indicated.

PMID- 22876555
TI  - Seizure due to somatostatin analog discontinuation in a case diagnosed as
      congenital hyperinsulinism novel mutation.
AB  - The most common reason for refractory hypoglycemia in newborns is congenital
      hyperinsulinism. We report a girl with congenital hyperinsulinism due to novel
      homozygous mutation (c.2041-25 G>A; aberrant splicing mutation) in the ABCC8 gene
      encoding SUR1 and during somatostatin analog (octreotide) discontinuation
      developed by nonhypoglycemic seizures. The newborn (birth weight of 3,750 g) was
      referred to our clinic because of hypoglycemic seizures at 4 h postnatal. On
      admission, blood glucose was 24 mg/dL and intravenous glucose infusion was
      started. The patient's insulin level was 27 mIU/mL during the hypoglycemic
      period. Phenobarbital (5 mg/ kg/day) was added because of short-acting
      generalized clonic seizures. Although the patient received high doses of
      diazoxide, esidrex, and octreotide approximately for 2 months, hypoglycemic
      episodes continued. Then the patient had near-total pancreatectomy, and pathology
      confirmed a diffuse form of congenital hyperinsulinism. There was homozygous
      mutation in the ABCC8 gene encoding SUR1, which confirmed the diagnosis of
      autosomal recessive congenital hyperinsulinism. During octreotide
      discontinuation, the patient developed non-hypoglycemic seizures, which were
      controlled by restarting the previous doses. In the light of in vitro and in vivo
      studies on antiepileptic effects of somatostatin, we believe that seizures in our
      case have developed secondary octreotide discontinuity.

PMID- 22876556
TI  - Simultaneous onset and similar course of type 1 diabetes mellitus in monozygotic
      twins (a 4-year follow-up).
AB  - We report a rare case of monozygotic (MZ) twins who developed simultaneous onset
      of type 1 diabetes mellitus (T1DM). Laboratory finding showed similar values of
      blood sugar, pH, glycosylated hemoglobin, and C-peptide. Urinary sugar and
      ketones were detected in both. Endocrine and immunological assessment showed
      similar results. No evidence (clinical or serological) of recent viral or
      bacterial infection was found. In the 4 years of follow-up, the twins also showed
      a similar course of disease. Concordance rates for T1DM are high in MZ twins;
      nevertheless, a simultaneous onset and a similar course of disease are unusual,
      as well as the HLA allelic variants of our patients. This extraordinary
      concordance in a pair of MZ twins could be the consequence of a greater
      environmental similarity or the role of genetic factors other than HLA genes in
      our twins.

PMID- 22876557
TI  - 17beta-hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous
      7 base pair deletion in 17betaHSD3 gene.
AB  - 17-beta-Hydroxysteroid dehydrogenase type 3 (17betaHSD-3) converts delta4
      androstenedione (A) to testosterone (T) in the testes. This enzyme plays a key
      role in androgen synthesis and it is essential for normal fetal development of
      male genitalia. 17betaHSD-3 deficiency is a rare cause of 46,XY disorders of
      sexual development. Here, we report a 16-year-old 46,XY patient with 17betaHSD-3
      deficiency raised as a female and significantly virilized in puberty. A
      homozygous 7 base pair deletion on exon 10 was determined in HSD17B3 gene (c.777
      783del_GATAACC). Our patient had one of the very rare mutations, which was
      previously unencountered in Turkish patients with 17betaHSD type 3, and she is
      the second reported case with this deletion.

PMID- 22876558
TI  - Clinical and image-guided chorioretinal findings in long-chain 3-hydroxyacyl
      coenzyme A dehydrogenase deficiency.
AB  - The purpose of this study is to report clinical, optical coherence tomography
      (OCT), and fluorescein angiogram/indocyanine green angiography (FA/ICG) findings
      in patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) enzyme
      deficiency in two siblings. A 13-year-old girl and her 14-year-old brother
      presented with progressive decrease in central vision. Clinically, there were
      blond-looking fundi, diffuse retinal pigment epithelial (RPE) disruption/atrophy
      in the macula and peripheral retina with choriocapillaris atrophy in both of
      them. OCT showed RPE irregularity and diffuse disruption of the RPE layer. FA/ICG
      imaging demonstrated transmitted choroidal fluorescence secondary to diffuse RPE
      atrophy with no evidence of leakage. Electroretinogram and electrooculogram
      findings were suggestive of primary abnormality of pigment epithelium. The boy
      died of cardiac/respiratory illness, whereas his sister is alive at the last
      follow-up. Abnormal chorioretinal findings in LCHAD patients should be carefully
      followed. Regular follow-up is recommended to monitor the ocular and systemic
      status.

PMID- 22876559
TI  - Influence of HLA DQ 2/8 genotypes in predisposing type 1 diabetes in siblings of
      a Saudi family with paternally inherited chromosomal translocations.
AB  - Type 1 diabetes is one of the most widely studied complex genetic disorders and
      the genes in human leukocyte antigen (HLA) locus are reported to account
      approximately 40%-50% of familial aggregation of type 1 diabetes. Genetic markers
      are helpful in assessing the risk of type 1 diabetes in the general population as
      well as in close relatives of a patient with type 1 diabetes. The major genetic
      determinants of this disease are polymorphisms of class II HLA genes encoding DQ
      and DR. The major susceptibility genes for type 1 diabetes are in the HLA region,
      and over 90% of patients carry genotypes DR4, DQ8 and/or DR3, DQ2. Absence of the
      above alleles makes type 1 diabetes very unlikely, especially if the subject
      carries protective genotypes such as DR2 and/or DQ6. In this brief report of a
      consanguineous Saudi family, four offsprings inherited one or both of balanced
      reciprocal translocations from their father. Two offsprings, one with a
      translocation and the other without, developed type 1 diabetes during early
      childhood. Both these diabetic children were found to have HLA genotype DQ 2/8,
      whereas the father and the youngest daughter, both carrying two sets of balanced
      translocations as well as the protective HLA genotype DQ6, were free of diabetes
      during several years of observation. This underscores the influence of HLA
      genotype DQ 2/8 in the susceptibility and DQ6 in the protective effect on type 1
      diabetes even in individuals with gross chromosomal abnormalities.

PMID- 22876560
TI  - An unusual association between growth hormone deficiency and a middle cranial
      fossa arachnoid cyst.
AB  - Middle cranial fossa arachnoid cysts (MFACs) are frequently asymptomatic. Here,
      we report the case of a 10-year-old boy with growth hormone deficiency (GHD) and
      an MFAC. His linear growth had followed the -2.5 SD line. On physical
      examination, his height was 120.8 cm (-2.6 SD), and the level of insulin-like
      growth factor 1 was low (87 ng/mL). GH provocative tests revealed GHD and brain
      magnetic resonance imaging (MRI) revealed an MFAC. We started treatment with GH
      replacement therapy (0.175 mg/kg/week). At the age of 12 years and 9 months,
      there were no interval changes in the features of the MFAC on the brain MRI. As
      his height was 145.5 cm (-1.7 SD) at the age of 13 years and 4 months, the
      therapy seems to be successful without sequelae. GH replacement therapy is
      suggested to be safe and effective to treat patients with GHD associated with
      arachnoid cysts.

PMID- 22876561
TI  - Type 2 diabetes mellitus in a young girl: ominous presentation and atypical
      course.
AB  - OBJECTIVE: To report a 7-year-old young girl who was found unresponsive and found
      to be in severe diabetic ketoacidosis (DKA). Presence of obesity, acanthosis
      nigricans, and strong family history of type 2 diabetes mellitus (T2DM) along
      with negative pancreatic autoimmune antibody evaluation suggested T2DM as the
      culprit. METHODS: We present clinical findings, laboratory test results, and
      imaging reports as well as follow-up on this unique presentation of T2DM.
      RESULTS: A 7-year-old girl was found unresponsive at home. Initial evaluation
      demonstrated severe DKA and diminished neurologic status. CT-scan of the head did
      not demonstrate cerebral edema. Her neurologic status deteriorated dramatically
      on four separate occasions requiring reintubation twice. She was transitioned to
      intensive insulin management, requiring up to 2 units/kg/day insulin. Her insulin
      sensitivity improved dramatically prior to discharge. Now 18 months from
      diagnosis, she remains on basal insulin and metformin. CONCLUSIONS: New-onset
      T2DM is an increasing event in youth. Reports suggest that these youth may
      acutely deteriorate as opposed to the typical longer duration of onset in youth
      with new-onset type 1 diabetes mellitus. Attention to effective screening of
      those at risk and increasing public awareness of T2DM in youth is important and
      may reduce the risk of such dreadful presentations as described in the current
      report. The balance between insulin deficiency and insulin resistance is variable
      at different phases of the condition. This highlights the need for study of the
      natural history of T2DM in youth.

PMID- 22876562
TI  - Marked increase of final height by long-term aromatase inhibition in a boy with
      idiopathic short stature.
AB  - Growth hormone (GH) is the most frequently used treatment in children with
      idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an
      experimental state, and both final height (FH) and long-term efficacy data in ISS
      have not been published. We present a 14.5-year-old boy with ISS and a height of
      142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age
      (BA) of 13.5-14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154
      cm (SDS -3.77)-158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was
      169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15
      cm. No permanent side effects of the medication have been observed. Both a
      transient occurrence and a spontaneous recovery of decreased bone mineral
      apparent density were seen, verified by dual-energy X-ray absorptiometry. Spinal
      magnetic resonance imaging revealed no vertebral abnormalities. All therapy might
      be an effective and low-cost alternative to the use of GH. Further controlled
      trials should prove efficacy and safety of long-term AI therapy in boys with ISS.

PMID- 22876563
TI  - A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase
      domain of the insulin receptor gene complicated by medullary sponge kidney.
AB  - Rabson-Mendenhall syndrome (RMS) is a genetic disorder characterized by severe
      insulin resistance and somatic characteristics. Recombinant insulin-like growth
      factor 1 (r-IGF-1) is used to treat RMS, as the IGF-1 and insulin receptors share
      homology. However, the effect of r-IGF-1 varies in patients and it is difficult
      to manage metabolic status appropriately in r-IGF-1 resistant cases. We report a
      Japanese boy with RMS who showed resistance to r-IGF-1 therapy and a novel
      mutation in the insulin receptor in the tyrosine kinase domain. Mutations in this
      region disturb tyrosine kinase catalytic activity in IGF-1 receptors as a result
      of dominant negative effects. We consider this mutation to be the cause of
      resistance to r-IGF-1. The patient also exhibited radiographical features of
      medullary sponge kidney and had severe nephrocalcinosis and hypokalemia,
      indicating Bartter syndrome. However, analysis revealed no mutations in the
      responsible genes and the etiology of the renal abnormalities therefore remains
      unknown.

PMID- 22876565
TI  - Septo-optic dysplasia and hemophagocytic lymphohistiocytosis in an infant.
AB  - Macrophage activation in hemophagocytic lymphohistiocytosis (HLH) leads to severe
      inflammation resulting in cytopenias and multi-organ dysfunction. Septo-optic
      dysplasia (SOD) is an as-yet unaffiliated disorder that manifests with optic,
      hepatic, endocrine and/or constitutional defects. We detail the first reported
      occurrence of both HLH and SOD in one patient. This two-month old patient
      presented with acute hepatitis, direct hyperbilirubinemia, anemia and
      thrombocytopenia. Treatment followed standard of care practices for SOD and HLH.
      The patient subsequently underwent an allogeneic bone marrow transplant within
      eight months of diagnosis and remained in full remission at day +90. We suggest
      considering a diagnosis of HLH in patients with SOD who present with severe liver
      failure refractory to standard therapy.

PMID- 22876564
TI  - Persistent hyperinsulinemic hypoglycemia of infancy.
AB  - Congenital hyperinsulinism (CHI) is the most frequent cause of severe, persistent
      hypoglycemia in infancy and childhood. We report a case of CHI with diffuse
      pancreatic abnormality diagnosed preoperatively using the 68Ga octreotide (DOTA
      NOC) positron emission tomography scan. Genetic analysis revealed homozygous
      ABCC8 splicing mutation. Subtotal (95%) pancreatectomy was done, and the infant
      remained euglycemic and was discharged on breast feeds. The patient is
      continuously followed up and is asymptomatic until 9 months.

PMID- 22876566
TI  - Primary familial hypomagnesemia syndrome: a new approach in treatment.
AB  - Primary familial hypomagnesemia is a rare genetically determined disorder
      characterized by a selective defect in magnesium (Mg) absorption. Mutations of
      the transient receptor potential melastatin 6 (TRPM6) gene, which codes for
      TRPM6, the basic channel for intestinal Mg absorption and a new member of the
      transient receptor potential (TRP) family of cation channels, result in primary
      hypomagnesemia. Here we present a 14-year-old Turkish girl whose first symptoms
      manifested as neonatal tetany at 17 days old. During her follow-up, she was
      mainly taking high-dose oral Mg therapy. However, intravenous Mg and calcium (Ca)
      therapies were given during symptomatic attacks. When her requirements for Ca and
      Mg were increased during the pubertal growth period, which overlapped with
      increased loss of Mg during the summer, oral Ca and active vitamin D (calcitriol,
      Rocaltrol) were added. Calcitriol is needed because hypomagnesemia results in
      decreased production and resistance to the actions of active vitamin D, which
      leads to the disturbance of intracellular signal transmission. Although high-dose
      oral Mg is reported as a sufficient therapy in most of the patients with primary
      familial hypomagnesemia, addition of active vitamin D to the usual oral Mg and Ca
      therapy seems very useful, as in this patient.

PMID- 22876567
TI  - A case of congenital hypothyroidism in PHACE syndrome.
AB  - Although hemangiomas, benign tumors of vascular origin, are very common among
      children and represent the most frequent benign tumor at that age, their
      association with other malformations constitutes a rare neurocutaneous disorder
      called PHACE syndrome. This condition is characterized by posterior fossa
      anomalies, hemangioma of the face, arterial alterations, cardiac defects, and eye
      anomalies (as represented by the acronym PHACE); sternum defects,
      endocrinopathies, and thyreopathies may be present as well. In this report, we
      describe a case of congenital hypothyroidism due to an empty thyroid site, as
      demonstrated by ultrasound, in an Italian child.

PMID- 22876568
TI  - Is vitamin D deficiency a feature of pediatric celiac disease?
AB  - BACKGROUND: Celiac disease (CD) is an autoimmune enteropathy characterized by
      villus atrophy and malabsorption of essential nutrients. Vitamin D deficiency has
      been described in autoimmune diseases, but its status in prepubertal children
      with CD has not been adequately studied. OBJECTIVE: To determine the vitamin D
      status of prepubertal children with CD. STUDY DESIGN: A retrospective study of
      prepubertal children aged 3-12 years with CD (n=24) who were compared to
      prepubertal, non-CD children of the same age (n=50). Children were included in
      the study if they had a diagnosis of CD by intestinal biopsy, and were not on a
      gluten-free diet (GFD). Patients were excluded if they had diseases of calcium or
      vitamin D metabolism, or were receiving calcium or vitamin D supplementation or
      had other autoimmune diseases. All subjects had their serum 25-hydroxyvitamin D
      [25(OH)D] level measured. RESULTS: There was no difference in 25(OH)D level
      between the CD and non-CD children (27.58 +/- 9.91 versus 26.20 +/- 10.45, p =
      0.59). However, when the patients were subdivided into obese and non-obese
      groups, the non-obese CD patients had a significantly higher 25(OH)D level than
      the obese normal children (28.39 +/- 10.26 versus 21.58 +/- 5.67, p = 0.009). In
      contrast, there was no difference in 25(OH)D level between non-obese CD patients
      and non-obese normal children (28.39 +/- 10.26 versus 30.64 +/-12.08, p = 0.52).
      The season of 25(OH)D measurement was not a significant confounder (p =0.7).
      CONCLUSIONS: Our data showed no difference in 25(OH) D levels between normal
      children and those with CD when adjusted for body mass index.

PMID- 22876569
TI  - Authors' reply to "The appropriate use of sensitive tests of hypothalamic
      pituitary-adrenal axis suppression".

PMID- 22876570
TI  - Diagnosis of non-alcoholic fatty liver disease in obese children.

PMID- 22876571
TI  - Microduplication 22q11.2: a description of the clinical, developmental and
      behavioral characteristics during childhood.
AB  - Microduplication 22q11.2 is a recently discovered genomic disorder. So far,
      targeted research on the cognitive and behavioral characteristics of individuals
      with this microduplication is limited. Therefore, 11 Flemish children (3-13 years
      old) with a microduplication 22q 1.2 were investigated in order to describe their
      clinical, developmental and behavioral characteristics. We measured their general
      intelligence, visual-motor capacities, attention, behavioral problems and
      characteristics of autism. In addition, there was an interview with the parents
      on developmental history and we reviewed available information from other
      specialists. The results show that the cognitive and behavioral phenotype of the
      children with microduplication 22q.11.2 is very wide and heterogeneous. Some of
      the children have a cognitively nearly normal development whereas others are more
      severely affected. All children had some degree of developmental delay and some
      of them have an intellectual disability. The most common clinical features
      include congenital malformations such as heart defects and cleft lip, feeding
      problems, hearing impairment and facial dysmorphism. The most common non-medical
      problems are learning difficulties, motor impairment, attention deficits, social
      problems and behavioral problems. There is no correlation between the size of the
      duplication and the phenotype.

PMID- 22876572
TI  - Thiamine-responsive megaloblastic anemia syndrome: a novel mutation.
AB  - The thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal
      recessive disorder characterized by diabetes mellitus, megaloblastic anemia and
      sensorineural hearing loss due to mutations in SLC 19A2 that encodes a thiamine
      transporter protein. The disease can manifest at any time between infancy and
      adolescence, and not all cardinal findings are present initially. The anemia
      typically improves significantly with pharmacological doses of thiamine. Variable
      improvement in diabetes is also noted. However, the hearing loss is apparently
      irreversible, although a delay in the onset of deafness may be possible. We
      present a 2-year old girl with non-autoimmune diabetes mellitus and anemia in
      whom we found a novelc.95T>A (leu32X) mutation in the SLC19A2 gene in this
      study.Our patient with this new mutation did not suffer from hearing loss.

PMID- 22876573
TI  - X-linked Aarskog syndrome: report on a novel FGD1 gene mutation. Executive
      dysfunction as part of the behavioural phenotype.
AB  - Aarskog-Scott syndrome [OMIM 100050] is a predominantly X-linked disorder that is
      phenotypically characterized by short stature, craniofacial dysmorphisms,
      brachydactyly and urogenital abnormalities. The level of intelligence shows a
      great variability and no specific behavioural phenotype has been described so
      far. In about 20 percent ofAarskog families, a mutation in the FGD1 gene located
      in Xp11.21 can be identified. In the present study, four affected males from the
      fourth generation of a large Dutch family (published in 1983 by Van de Vooren et
      al. (41)) are described. A novel FGD1 missense mutation (R402W) at position 1204
      (1204C>T) was demonstrated. In the patients, the level of intelligence varied
      between normal and severely disabled. Their behavioural profile showed, among
      others, elements of attention deficit hyperactivity disorder, primarily reflected
      by impaired executive attentional processes that may be sensitive to systematic
      training.

PMID- 22876574
TI  - Warburg micro syndrome in two children from a highly inbred Turkish family.
AB  - Warburg Micro syndrome (WMS) was first reported by Warburg in 1993. The cardinal
      features are microcephaly, microphthalmia, congenital cataract and intellectual
      disability. We report on two children from a highly inbred family with
      microcephaly, congenital cataract, optic atrophy, hypotonia and severe
      psychomotor retardation. This phenotype is similar to other reported rare
      entities and especially to the family reported by Warburg. Four other children in
      the same family may also have been affected. In this report, the symptoms and
      features of our cases are compared with the Warburg Micro syndrome patients in
      literature.

PMID- 22876575
TI  - A report of three patients with MMP2 associated hereditary osteolysis.
AB  - Osteolysis syndromes are rare hereditary disorders characterized by destruction
      and resorption of affected bones. The current study adds three new patients from
      two unrelated consanguineous families with a severe form of inherited osteolysis.
      Clinical examination, radiological, biochemical, ultrastructural and molecular
      studies were conducted. Clinical and radiological studies suggested the diagnosis
      of Torg-Winchester syndrome. The three affected patients were homozygous for
      novel MMP2 gene mutations which confirmed the diagnosis. Our patients are the
      first to be reported from Egypt thus, supporting the pan ethnic nature of the
      disease.

PMID- 22876576
TI  - A new family with autosomal dominant porencephaly with a novel Col4A1 mutation.
      Are arachnoid cysts related to Col4A1 mutations?
AB  - Porencephaly is an extensively encountered condition in pediatric neurology
      practice and leads to serious morbidity with its complications. Important
      etiological factors are trauma, hemorrhage, infection and thrombophilic factors
      that may cause destruction in the developing brain. Col4A1 mutations were also
      shown in familial porencephaly cases. We describe two siblings with porencephaly,
      hemiparesis, epilepsy, atrophic kidney in one of the siblings and asymptomatic
      mothers with an arachnoid cyst. We performed Col4A1 gene mutation screening and
      detected a novel mutation in mother and both of the children. This family has
      some features previously undescribed in patients with mutations of Col4A1 gene
      like atrophic kidney in one sibling and arachnoid cyst in the mother. We discuss
      here the possible relationship between these abnormalities and the mutation.

PMID- 22876577
TI  - Phenotypic features of pure 9p deletion in a male infant include cryptorchidism,
      congenital heart defects and postaxial polydactyly.
AB  - We report a 2 1/2-year-old male infant with a karyotype of 46,XY,del(9)(p22) and
      the phenotypic features of craniofacial dysmorphisms, hypotonia, psychomotor
      developmental delay, mental retardation, ventricular septal defect, atrial septal
      defect, cryptorchidism and postaxial polydactyly of the fingers. A rudimentary
      poorly developed extra digit in the ulnar side of the fifth finger was observed
      in each hand. The present case adds to the literature of postaxial hexadactyly of
      the fingers in chromosome 9p deletion syndrome. We suggest that 9pter-p22 may
      contain genetic loci associated with human postaxial polydactyly.

PMID- 22876578
TI  - Partial monosomy 9p (9p22.2-->pter) and partial trisomy 18q (18q21.32-->qter) in
      a female infant with anorectal malformations.
AB  - We report a female infant with a karyotype of
      46,XX,der(9)t(9;18)(p22.2;q21.32)pat and the phenotypic features of craniofacial
      dysmorphisms, developmental delay, hypotonia, horizontal nystagmus, strabismus,
      congenital heart defects, clubfoot, and anorectal malformations with an anterior
      ectopic anus and a stenosed anal opening. Array comparative genomic hybridization
      revealed a 16.93-Mb deletion at 9p24.3-p22.2 encompassing the FREM1 gene and a
      20.43-Mb duplication at 18q21.32-q23 encompassing the PIGN gene. We speculate
      that dual genome imbalances in FREMI at 9p22.3 and in PIGN at 18q21.3 are most
      likely responsible for the abnormal development of anorectum in this patient.

PMID- 22876579
TI  - Tertiary trisomy of 10p15.pter and 14pter.ql3 due to maternal translocation
      t(10;14)(p15;q13).
AB  - Double partial trisomy resulting from 3:1 segregation of the respective
      chromosomal segments of the chromosomes involved in a balanced translocation in
      meiosis is rarely reported in the literature. We present here a first patient
      with multiple congenital malformations associated with double partial trisomy of
      10pter-p15 and 14pter-q13 resulting from 3:1 segregation of maternal balanced
      translocation t(10;14)(p15;q13). Proximal partial trisomy of chromosome 14 and
      subterminal trisomy of the short arm of the chromosome 10 are rare. The present
      case is the first case with double partial trisomy of these segments resulting
      from 3:1 segregation of a maternal balanced translocation.

PMID- 22876580
TI  - Pure distal 9p deletion in a female infant with cerebral palsy.
AB  - We report cytogenetic and molecular characterization of a 15.63-Mb pure distal
      deletion of chromosome 9p (9p22.3-->pter) in a l 1/2-year-old female infant with
      cerebral palsy and diffuse cerebral dysfunction. The deletion is of paternal
      origin and encompasses the genes of ANKRDS15, DOCK8, FOXD4 and VLDLR. We discuss
      the genotype-phenotype correlation in this case with neurological dysfunction and
      a distal 9p deletion of paternal origin.

PMID- 22876581
TI  - Pure distal 11q deletion without additional genomic imbalances in a female infant
      with Jacobsen syndrome and a de novo unbalanced reciprocal translocation.
AB  - We report a neonate with pure deletion of distal 11q (11q23.3-->qter) and
      Jacobsen syndrome. The patient had growth restriction, petechiae,
      thrombocytopenia, dilation of renal pelvis, congenital heart defects, and
      seizures. Array comparative genomic hybridization revealed a 15.8-Mb deletion
      from 11q23.3 to 11q25 without genomic imbalances in other chromosomes.
      Cytogenetic analysis revealed a karyotype of 46,XX,der(7)(7pter-
      >7q32),der(11)(11pter--> 11q23.3::7q32-->7qter). The parental karyotypes were
      normal. This is the first report of pure distal 11q deletion without additional
      genomic imbalances in a patient with Jacobsen syndrome and a de novo unbalanced
      reciprocal translocation.

PMID- 22876582
TI  - A short rib polydactyly syndrome overlapping both lethal and nonlethal types.
AB  - Short rib polydactyly syndrome (SRPS) type II is a rare, autosomal recessively
      inherited, lethal skeletal dysplasia characterized by polydactyly, short limbs,
      short and horizontal ribs, a short ovoid tibia and major organ anomalies. We
      report a patient with a fetus with SRPS type II that presented at the 19th week
      of pregnancy for amniocentesis because of maternal age. During ultrasound pre
      axial synpolydacytly, a short and ovoid tibia, nuchal edema, vertebral
      irregularities, hypoplastic thorax with short ribs and talipes were detected. All
      of the extremities were under the 5th percentile. Thorax-abdomen ratio was 0,56.
      The family was counselled for a diagnosis of lethal SRPS. After termination of
      pregnancy, radiological and histopathological examination allowed us to reach the
      diagnosis ofMajewski syndrome (SRPS type II). SRPSs are a continuous spectrum of
      both lethal and nonlethal forms. Prenatal diagnosis and termination depending on
      ultrasound findings should be done very precociously considering different
      phenotypic expressions, even in families previously affected by a lethal SRPS.

PMID- 22876583
TI  - Double partial trisomy of 6p23-pter and 9pter-q21.2 in a neonate resulting from
      4:2 meiotic segregation of a maternal complex t(6;7;9)(p23;p15;q21.2)
      translocation.
AB  - We report, a newborn presenting multiple congenital abnormalities with karyotype;
      47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2-->
      pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal
      daughter were carriers of a complex chromosomal rearrangement with karyotypes;
      46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case
      the extra derivative chromosome was the result of a 4:2 segregation of the
      chromosomes involved in translocation during oogenesis. Double partial trisomy in
      newborns resulting from 4:2 segregation is a rare event, and double partial
      trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to
      date.

PMID- 22876584
TI  - Does higher NORs expression affect the developmental stages of Down syndrome
      infants?
AB  - BACKGROUND: The nucleolar organizer regions (NORs) are localized at the secondary
      constriction of the five pairs of acrocentric chromosomes (13, 14, 15, 21 and 22)
      in human. MATERIALS AND METHODS: To evaluate whether increasing AgNOR protein
      synthesis effects or not the development of babies/children, 25 Down syndrome
      patients were included in this study. Firstly, the Ankara Development Screening
      Inventory (AGTE) test was performed. Then the buccal epithelial cells of patients
      were taken via a sterile toothpick on clean glass slides and spreaded and AgNOR
      staining technique was applied to the slides of each individual. Mean NOR
      area/Total nucleus area (NORa/TNa) were evaluated for each nucleus using a
      special computer program. RESULTS: The mean NORa/TNa was found to be 3.8+/-1.16.
      According to these data, a significant correlation was not evident between the
      NORa/TNa and developmental stages (p>0.05). CONCLUSIONS: There is no correlation
      between extra energy spending for NOR protein synthesis and developmental
      deficiency.

PMID- 22876585
TI  - A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash
      syndrome.
AB  - Denys-Drash syndrome (DDS) is a rare disorder characterized by glomerulopathy,
      genital abnormalities and predisposition to Wilms' tumor. It is associated with
      constitutional Wilms'tumor suppressor 1 (WT1) gene mutations, in which the
      majority being missense mutations in the zinc-finger region. Here, we present a
      newborn with DDS, associated with a novel heterozygous missense mutation,
      p.Asp396His, on exon 9 of WT1.

PMID- 22876586
TI  - A 7q11.23 microduplication patient with cerebral palsy and facial dysmorphism.
AB  - We report an 11year-old female with 7q11.23 microduplication detected by an array
      CGH test performed because of her atypical facial appearance while being followed
      up with diagnoses of epilepsy and cerebral palsy at the pediatric neurology
      department since she was 3 months old. We emphasize that the facial phenotype by
      itself should arise suspicion of the 7q11.23 duplication.

PMID- 22876587
TI  - Bartsocas-Papas syndrome with variable expressivity in an Egyptian family.
AB  - Bartsocas-Papas syndrome (BPS) is an autosomal recessively inherited sublethal
      popliteal pterygium condition characterized by intrauterine or neonatal death,
      severe popliteal webbing, oligosyndactyly, ankyloblepharon, orofacial clefts,
      intraoral filiform bands and genital anomalies. Internal organ involvement has
      seldom been identified. We report on a 3 years old female patient of healthy
      first cousin parents with BPS. She presented with orofacial clefting, severe
      popliteal webs, club feet, oligosyndactyly of the toes, hypogenitalism and normal
      hands and internal organs. Ankyloblepharon and filiform bands between the
      alveolar ridges were evident at birth. Pedigree analysis revealed a more severely
      affected female sib, who died a few minutes after birth with additional
      manifestations including near complete lip fusion without oral cleft, complete
      syndactyly in both hands and an omphalocele. Linkage was excluded to the IRF6
      gene; a candidate gene implicated in the Van der Woude and popliteal pterygium
      syndromes, with overlapping features with BPS. To our knowledge, this is the 5th
      surviving patient with this syndrome in the literature. In this report, we also
      discuss the proposed pathogenetic mechanisms for BPS and compare our patients
      with similarly described cases as well as overlapping spectrum of other popliteal
      pterygium syndromes. Our findings provide further evidence of intrafamilial
      clinical heterogeneity in families with BPS.

PMID- 22876588
TI  - A new clinical presentation associated with pontine clefting, hyperpigmentation
      and short stature in addition to craniofacial, cardiac and developmental
      anomalies.
AB  - We report on a 13-year-old girl who was the first child of nonconsanguineous
      parents, and who suffered from short stature accompanied with mental retardation,
      generalized hyperpigmentation of the skin and craniofacial findings. Her
      cardiological examination revealed atrial septal defect, mitral valve prolapsus
      and atrial septal aneurysm. Brain scans revealed dilatation of the third and
      lateral ventricles and a pontine cleft. Growth hormone (GH) deficiency was
      observed during the evaluation of GH/IGF-I axis. All the laboratory tests
      performed including metabolic screening, conventional karyotype and
      oligonucleotide array were normal. Mutation analysis of the C2ORF3 7 gene
      revealed no mutation. The clinical signs seen in this patient likely represent a
      new dysmorphological syndrome which has not been previously described.

PMID- 22876589
TI  - Structural chromosomal abnormalities in patients with mental retardation and/or
      multiple congenital anomalies: a new series of 24 patients.
AB  - Chromosomal abnormalities are a major cause of mental retardation and/or multiple
      congenital anomalies (MCA/MR). Screening for these chromosomal imbalances has
      mainly been done by standard karyotyping. The objective of this study was to
      report standard chromosome analysis and FISH screening of a series of 24 patients
      with MCA/MR. Structural chromosomal abnormalities were detected in 24 alterations
      and included 5 deletions, 2 duplications, 6 unbalanced translocations, 3
      inversions, 2 insertions, 3 derivative chromosomes, 2 marker chromosomes and 1
      isochromosome. We confirm that a high percentage of MCA/MR cases hitherto
      considered idiopathic is caused by chromosomal imbalances. We conclude that
      patients with MCA/MR should be routinely karyotyped.

PMID- 22876590
TI  - Molecular cytogenetic characterization of a case of primary amenorrhea with
      intrachromosomal triplication of the X chromosome q arm.
AB  - This is a unique case of intrachromosomal triplication of the X chromosome q arm
      detected with cytogenetic and spectral karyotyping in a 21-year-old woman with
      primary amenorrhea, who had been referred because of primary hypergonadotropic
      hypogonadism and Mullerian hypoplasia. Intrachromosomal triplications are rare
      rearrangements resulting in partial tetrasomy. Since 1993, at least 34 cases of
      intrachromosomal triplications involving 9 different chromosomes have been
      reported. The vast majority of the reported triplications are on the 15th
      chromosome, arised de novo and had middle inverted repetitions. In this report
      the genotype-fenotype correlation in a case of primary amenorrhea associated with
      triplication of the X chromosome q arm and the possible mechanisms of this
      rearrangement are discussed. Further the clinical usability of SKY analysis as a
      molecular cytogenetic tool in searching for genomic instability arising from
      cytogenetic rearrangements is highlighted.

PMID- 22876591
TI  - A cardio-facio-cutaneous syndrome case with tight Achilles tendons.
AB  - Cardio-facio-cutaneous syndrome (CFCS) is a multiple congenital anomaly disorder
      characterized by craniofacial features, cardiac defects, ectodermal anomalies and
      neurocognitive delay. Clinical findings of patients with CFCS show similarities
      to those of patients with Costello Syndrome (CS). CFCS and CS are caused by
      mutations in genes encoding proteins of the RAS-MAPK signaling pathway.
      Musculoskeletal findings including tight Achilles tendons and contractures of
      elbows, shoulders or hips have been reported in CS patients. However, limited
      extension of joints were observed in some patients with CFCS. According to the
      literature, no tight Achilles tendons have been reported in CFCS patients so far.
      In this case report, we present a male CFCS patient with tight Achilles tendons
      with a de-novo heterozygote N581D mutation in the BRAF gene detected by DNA
      sequence analysis.

PMID- 22876592
TI  - Pure duplication 21q21.2-->qter due to a rea(21) in a Down syndrome girl. Remarks
      on nomenclature.
AB  - We report on an 8-year-old girl with a typical Down syndrome phenotype and a
      46,XX,rea(21)(qter-->p12::q21.2-->qter).ish rea(21)(qter-->pl2::q21.2-->qter)(LSI
      21++,AML1++) karyotype; the mother had normal chromosomes but the father was
      unavailable. The great resemblance of the patient's rearranged chromosome to the
      rec(21)dup(q) from a parental pericentric inversion suggests that it would be
      better depicted as a recombinant-like chromosome. Altogether, 13 recombinant-like
      chromosomes of de novo or unknown (parents not karyotyped) origin have been
      described. Although these rearranged chromosomes should formally be described as
      derivatives because no parental inversion is identified, we underlie that the
      unofficial term recombinant-like would be more appropriate because no "multiple
      aberrations within a single chromosome" (as required by the ISCN) have been
      proved, not to mention that the term derivative usually designates abnormal
      chromosomes resulting from a translocation between non homologous chromosomes.
      Accordingly, we prefer to identify such rearrangements of a single chromosome
      precisely with the more neutral and sanctioned term rea (expanding its use to
      designate a rearranged chromosome) coupled with the lengthy description of the
      abnormal chromosome. We assume that the rea(21) chromosomes result from
      illegitimate recombination between non allelic homologous LCRs located in both
      the short and long arms.

PMID- 22876593
TI  - Emanuel syndrome due to unusual segregation of paternal origin.
AB  - Emanuel syndrome is an inherited chromosomal abnormality resulting from 3:1
      meiotic segregation from parental balanced translocation carrier
      t(11;22)(q23;q11), mostly of maternal origin. It is characterized by mental
      retardation, microcephaly, preauricular tag or sinus, ear anomalies, cleft or
      high arched palate, micrognathia, congenital heart diseases, kidney
      abnormalities, structural brain anomalies and genital anomalies in male. Here in,
      we describe a female patient with supernumerary der(22) syndrome (Emanuel
      syndrome) due to balanced translocation carrier father t(11;22) (q23;q11). She
      was mentally and physically disabled and had most of the craniofacial dysmorphism
      of this syndrome. Our patient had cleft palate, maldeveloped corpus callosum and
      hind brain with normal internal organs. Additionally, arachnodactyly,
      hyperextensibility of hand joints, abnormal deep palmar and finger creases, extra
      finger creases and bilateral talipus were evident and not previously described
      with this syndrome. Cytogenetic analysis and FISH documented that the patient had
      both translocation chromosomes plus an additional copy of der(22) with
      karyotyping: 47,XX,t(11; 22)(q23;q11),+der(22)t(11;22)(q23;q11). We postulated
      that this rare chromosomal complement can arise from; 2:2 segregation in the
      first meiotic division of the balanced translocation father followed by non
      disjunction at meiosis II in the balanced spermatocyte.

PMID- 22876594
TI  - A de novo supernumerary marker chromosome derived from chromosome 9p (9p13.1-
      >p23) associated with attention deficit and hyperactivity disorder.

PMID- 22876595
TI  - Phenotypic features associated with mosaic tetrasomy 9p in a 20-year-old female
      patient include autism spectrum disorder.

PMID- 22876596
TI  - High resolution microarray analysis in a patient with speech delay without cat
      like cry.

PMID- 22876597
TI  - Prostatitis: prevalence, health impact and quality improvement strategies.
AB  - Since its identification as a discrete entity, prostatitis has been a crippling
      and dreadful disease for the males and from then till date it is well recognized
      that it has continuously eluded the urologists and the practitioners and the
      patients were generally avoided. But the newer advent in research has changed the
      concept of the medical management of prostatitis that had been in stagnation for
      the past many years. The traditional myths related to the disease were continued
      to be unlighted with improved understanding of the distribution, cause and
      measures for the management of this disease. From herbal treatment used by the
      ethnic communities historically to today's modern treatment modules of
      antimicrobial and anti-inflammatory agents, though not very successful, but has
      embarked a light of hope in both practitioners and patients for the effective
      management of this condition, which has negatively affected the normal as well as
      intimate life of the sufferers. With newer and more widely accepted
      classification of the disease the practitioners and patients diagnosed with
      prostatitis now can hope for a better improvement and management of the disease.
      The present study tries to encompass the important and useful work reported by
      several workers and progress in the effective management of this awful condition.

PMID- 22876598
TI  - Solubility enhancement of simvastatin: a review.
AB  - Fairly soluble drugs in gastrointestinal (GI) media exhibit complete oral
      absorption, and thus good bioavailability. About 40% of drugs are not soluble in
      water in practice and therefore are slowly absorbed, which results in
      insufficient and uneven bioavailability and GI toxicity. Thus, most exigent phase
      of drug development practice particularly for oral dosage forms is the
      enhancement of drug solubility and thereby its oral bioavailability. Solubility,
      an important factor to achieve desired plasma level of drug for pharmacological
      response, is the phenomenon of dissolution of solid in liquid phase resulting in
      a homogenous system. This review describes various traditional and novel
      methodologies proposed for solubility enhancement of simvastatin, and ultimately
      improvement in its bioavailability. For simvastatin, solubility is a crucial rate
      limiting factor to achieve its desired level in systemic circulation for
      pharmacological response. Thus, problematic solubility of simvastatin is a main
      challenge for dosage form developing researchers. Various procedures, illustrated
      in this review, have been successfully employed to improve the simvastatin
      solubility for its bioavailability enhancement; however, successful improvement
      essentially depends on the assortment of technique. Among all the solubility
      enhancement techniques, solid dispersion method, in terms of ease and efficiency
      is most promising and routinely employed technique to resolve the solubility
      problems of simvastatin.

PMID- 22876599
TI  - High-performance liquid chromatographic determination of alpha-tocopherol in
      inclusion complexes with cyclodextrins.
AB  - A new high performance liquid chromatography (HPLC)-based method is proposed for
      the determination of vitamin E, free and in inclusion complexes with natural beta
      cyclodextrin and its 2-hydroxy derivative. The method has been validated on the
      basis of the following parameters: specificity, selectivity, linearity,
      precision, range and recovery.

PMID- 22876600
TI  - Quantitative analysis of norfloxacin by 1H NMR and HPLC.
AB  - 1H NMR and developed previously HPLC methods were applied to quantitative
      determination of norfloxacin in veterinary solution form for pigeon. Changes in
      concentration can lead to significant changes in the 1H chemical shifts of non
      exchangeable aromatic protons as a result of extensive self-association
      phenomena. This chemical shift variation of protons was analyzed and applied in
      the quantitative determination of norfloxacin. The method is simple, rapid,
      precise and accurate, and can be used for quality control of this drug.

PMID- 22876601
TI  - Sensitive determination of proteins by its quenching effect on fluorescence of
      new terbium(III) complex.
AB  - It is found that in hexamethylenetetramine (HMTA-HCl) buffer pH = 7.8, proteins
      can quench the fluorescence intensity of new terbium(III) complex with 6-[(1
      hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carbonyl)-amino]
      hexanoic acid (L). Based on this, a sensitive fluorimetric method for the
      determination of proteins is proposed. Under optimum conditions, the I0/I is in
      proportion to the concentration of protein in the range of 0.1-40.0 microg/mL for
      bovine serum albumin (BSA), 0.1-70.0 microg/mL for human serum albumin (HSA) and
      0.1-40.0 microg/mL for immunoglobulin G (IgG). Their detection limits (S/N = 3)
      are 0.03 microg/mL. The interaction mechanism for the luminescence quenching is
      also studied.

PMID- 22876602
TI  - Determination of Se(IV), Cd(II) and Pb(II) ions in homeopathic drugs by inversion
      voltammetry method.
AB  - The conditions for identification and quantification of Se(IV), Cd(II) and Pb(II)
      ions in homeopathic drugs by inversion voltammetry method with the use of EAGRAPH
      software were established. The studies proved that the method was of high
      sensitivity in established conditions. The detection limits were 0.66 microg/mL,
      0.08 microg/mL and 0.12 microg/mL for Se(IV), Pb(II) and Cd(II) ions,
      respectively. This method was characterized by repeatability of measurements, a
      wide range of linearity and satisfactory percent recovery.

PMID- 22876603
TI  - Biochemical activities of acetone extracts of Hyssopus angustifolius.
AB  - Antioxidant and antihemolytic activities of acetone extracts of Hyssopus
      angustifolius flowers, leaf and stems were investigated employing different in
      vitro and ex vivo assay systems. IC50, for 1,1-diphenyl-2-picryl hydrazyl (DPPH)
      radical-scavenging activity were 239.4 +/- 8.4 microg/mL for flowers, 357.8 +/-
      11.1 microg/mL for stems and 182.5 +/- 7.5 microg/mL for leaf. All extracts
      showed moderate nitric oxide scavenging activity. The leaf extract exhibited
      better hydrogen peroxide scavenging and Fe2+ chelating activity than the others
      (IC50 were 261.0 +/- 6.2 microg/mL for hydrogen peroxide and 534.0 +/- 9.9
      microg/mL for Fe3+ chelating activity). The extracts exhibited good antioxidant
      activity in linoleic acid peroxidation system and weak reducing power ability.
      The leaf extract showed better antihemolytic activity than the flower and stem
      (IC50 = 65.7 +/- 1.8 microg/mL).

PMID- 22876604
TI  - Synthesis of 2-oxoquinoline-3-carboxamide of ampicillin and amoxicillin as
      inhibitors of penicillin binding protein 1A of pseudomonas aeruginosa.
AB  - A series of ampicillin and amoxicillin derivatives were prepared by N-acylation
      with N1-substituted 1, 2-dihydro-2-oxoquinoline carboxylic acids by Schotten
      Baumann procedure and evaluated as inhibitors of Pseudomonas aeruginosa using
      molecular docking study. Most of the derivatives showed remarkableactivity
      against Gram positive and Gram negative bacteria in vitro.

PMID- 22876605
TI  - Synthesis and antimicrobial screening of N-[2-(2/4-substituted phenyl)-1-(5/6
      substituted 1H- benzimidazol-2-yl)vinyl]benzamides.
AB  - A series of (benzamidostyryl)benzimidazole derivatives were synthesized by
      hydrolyzing 2-phenyl-4-(substituted)benzylidene-5-oxazolones, the azlactone
      precursors in an acidic medium and treating the product with substituted o
      phenylenediamine (OPDA) in situ. The structures of the synthesized compounds were
      confirmed by spectral and elemental analyses. All synthesized compounds were
      screened for their in vito antimicrobial activities against some identifiable
      strains. Thereby, it was found that only nitro substituted benzimidazoles
      exhibited good to moderate antibacterial activity, while other derivatives were
      devoid of any antimicrobial effect.

PMID- 22876606
TI  - Synthesis and characterization of (E)-N'-(substituted
      benzylidene)isonicotinohydrazide derivatives as potent antimicrobial and hydrogen
      peroxide scavenging agents.
AB  - A series of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives were
      synthesized by coupling isoniazid with differently substituted aldehydes and
      benzophenones in the presence of absolute ethanol along with catalytic amount of
      glacial acetic acid. The structure of all the synthesized compounds were
      confirmed and characterized by using various spectral technique like IR, 1H NMR,
      13C NMR and mass spectroscopy. All the synthesized compounds were evaluated for
      their antimicrobial activity in terms of zone of inhibition, minimum inhibitory
      concentration, minimum bactericidal concentration and minimum fungicidal
      concentration in camparison to the standard drugs. The results revealed that all
      synthesized compounds had shown potent to mild biological activity. Among the
      synthesized derivatives, (E)-N'-(3,4-dimethoxybenzylidene)isonicotinohydrazide
      2e, (E)-N'-(3,4,5-trimethoxybenzylidene)isonicotinohydrazide 2f and (E)-N'-(4
      hydroxy-3-methoxybenzylidene)isonicotinohydrazide 2g were found to be the most
      effective antimicrobial compounds, whereas compounds 2g and 2k were the most
      potent antioxidants with significant hydrogen peroxide scavenging activity.

PMID- 22876607
TI  - Antitumor and antimicrobial activities of some hetero aromatic benzofurans
      derived from naturally occurring visnagin.
AB  - Bromination of visnaginone (1) yielded the dibromo derivative (2), which upon
      methylation with methyl iodide gave 1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl)
      ethanone (3). Compound (3) reacted with dimethylformamide dimethylacetal to give
      (4). The reaction of (3) with aromatic aldehydes namely (vanillin, benzaldehyde
      and 3-anisaldehyde) in ammonium acetate, malononitrile and/or butyric
      cyanoanhydride gave the 2-amino substituted nicotinonitriles (5a-c) and the 2
      hydroxyl substituted nicotinonitriles (7a-c), respectively, while in piperidine
      gave (E)-1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl)-3-(substituted)prop-2-en-l
      one (11a-c). (5a) was hydrolyzed with sulfuric acid on cold to give the nicotinic
      acid derivative (6a). When compound (3) reacted with hydrazines and aromatic
      amines, it gave the Schiff bases (8a,b) and (10a,b), respectively. (8b) reacted
      with thioglycolic acid to give the thiazolidin-4-one (9b). When (11a-c) reacted
      with thiourea, it gave the pyrimidine derivatives (12a-c). (11a,b) also reacted
      with butyric cyanoanhydride and hydroxylamine hydrochloride to give (13a,b) and
      (15a,b), respectively. When the carboxylate (13a) was treated with 2,4
      dinitroaniline, it gave the carboxamide (14a). Compounds (11b,c) reacted with
      hydrazine derivatives (hydrazine hydrate and phenylhydrazine) yielding the
      substituted pyrazole derivatives (16b,c) and (17b,c), respectively. All the
      structures of the synthesized compounds were elucidated by elemental analyses and
      spectral data. The newly synthesized benzofuran compounds showed a strong to
      moderate cytotoxicity against liver HEPG2 cancer cell line compared to 5
      fluorouracil and doxorubicin (the anticancer agents). Compounds (2, 6a, 13a, 14a,
      16c and 17b) were the most active compounds in descending order. The synthesized
      compounds were also tested for their antimicrobial activity. Compound (10b)
      showed the highest activity against all the tested strains followed by 6, 10a,
      5a, 8b and 7a in descending order.

PMID- 22876608
TI  - Antimicrobial activity of new synthesized [(oxadiazolyl)methyl]phenytoin
      derivatives.
AB  - A number of substituted phenytoin derivatives in addition to their sugar
      hydrazones were newly synthesized. Furthermore, the corresponding derived 1,3,4
      oxadiazole and their thioglycoside as well as their acyclic analogs were
      prepared. The antimicrobial activity of the prepared compounds was evaluated
      against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Aspergillus
      niger and Candida albicans. The dithiohydrazone as well as oxadiazole thiole
      derivatives, sugar hydrazones and acyclic nucleoside analogs were the highly
      active compounds.

PMID- 22876609
TI  - Anticancer activity of new (tetrazol-5-yl)methylindole derivatives and their
      acyclic c-nucleoside analogs.
AB  - New (tetrazol-5-yl)methylindole derivatives were synthesized from 2-phenylindole.
      Furthermore, the sugar acetyl hydrazones of the tetrazole derivatives as well as
      their derived acyclic C-nucleoside analogs were prepared. The synthesized
      compounds were studied for their anticancer activity against human liver
      carcinoma cell line (HepG2) and the results showed that arylidine substituted
      tetrazole derivatives 7c and 7d were the most active.

PMID- 22876610
TI  - Synthesis, characterization and antibacterial activity of mixed ligand
      dioxouranium complexes of 8-hydroxyquinoline and some amino acids.
AB  - Mixed ligand complexes of dioxouranium(VI) of the type [UO2(Q)(L)-2H2O] have been
      synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O-
      donor amino acids (HL) such as L-lysine, L-aspartic acid and L-cysteine as
      secondary ligands. The metal complexes have been characterized on the basis of
      elemental analysis, electrical conductance, room temperature magnetic
      susceptibility measurements, spectral and thermal studies. The electrical
      conductance studies of the complexes in DMF in 10(-3) M concentration indicate
      their non-electrolytic nature. Room temperature magnetic susceptibility
      measurements revealed diamagnetic nature of the complexes. Electronic absorption
      spectra of the complexes show intra-ligand and charge transfer transitions,
      respectively. Bonding of the metal ion through N- and O- donor atoms of the
      ligands is revealed by IR studies and the chemical environment of the protons is
      also confirmed by NMR studies. The thermal analysis data of the complexes
      indicate the presence of coordinated water molecules. The agar cup and tube
      dilution methods have been used to study the antibacterial activity of the
      complexes against the pathogenic bacteria S. aureus, C. diphtherinae, S. typhi
      and E. coli.

PMID- 22876612
TI  - Phenolic acids in the flowers and leaves of Grindelia robusta Nutt. and Grindelia
      squarrosa Dun. (Asteraceae).
AB  - 2D-TLC and RP-HPLC methods were applied to qualitatively determinate free
      phenolic acids and those liberated by acid and alkaline hydrolysis in the flowers
      and leaves of G. robusta and G. squarrosa. The presence of eleven phenolic acids,
      namely: caffeic, chlorogenic, p-coumaric, p-hydroxybenzoic, ferulic, gallic,
      protocatechuic, vanillic salicylic, p-hydroxyphenylacetic and ellagic acids was
      determined. Quantitative estimate of phenolic acids, expressed as caffeic acid,
      has been analyzed by the method described in the Polish Pharmacopoeia VIII. The
      content of phenolic acids in G. robusta reached 7.33 mg/g and 6.23 mg/g for
      flowers and leaves, respectively. The flowers and leaves of G. squarrosa were
      characterized by similar level of phenolic acids, namely 6.81 mg/g and 6.59 mg/g,
      respectively.

PMID- 22876611
TI  - Antioxidant, antihemolytic and nephroprotective activity of aqueous extract of
      Diospyros lotus seeds.
AB  - This study was conducted to quantitatively evaluate the antioxidant,
      antihemolytic and nephroprotective effects of Diospyros lotus seeds extract in
      experimental in vitro and in vivo models. Antioxidant potential of Diospvyos
      lotus seeds extract was examined by employing seven in vito models i.e., DPPH,
      nitric oxide and hydrogen peroxide radicals scavenging activity, iron ion
      chelating, reducing power and lipid peroxidation through linoleic acid.
      Antihemolytic activity of extract was examined against hydrogen peroxide-induced
      erythrocytes hemolysis. Also, nephroprotective effect of extract against
      gentamicin (GM)-induced renal injury was evaluated. Renal injury was achieved by
      injecting 100 mg/kg, intraperitoneally (i.p.) of GM in normal saline. Extracts
      were administrated i.p. in doses 200 and 400 mg/kg. Blood samples were examined
      for serum creatinine and blood urea nitrogen after 10 consecutive days of
      treatment. Results show that extract showed different level of antioxidant and
      antihemolytic activity in the studied models. Also, results show that GM-induced
      nephrotoxic animal model was successfully constructed. Extract attenuated the
      gentamicin-induced increase in level of serum creatinine and blood urea nitrogen.
      The present study shows that the extract offered significant biological action
      compared with standard compound.

PMID- 22876613
TI  - Acute and chronic hypoglycemic activity of Sida tiagii fruits in N5
      streptozotocin diabetic rats.
AB  - Herbal prescriptions have been recognized as potentially valid by the scientific
      medical establishment, and their use has been increasing. Sida tiagii Bhandari
      (Sida pakistanica; family-Malvaceae), a native species of the Indian and Pakistan
      desert area, popularly known as "Kharenti" in India; is used as a folk medicine.
      In the present study, various fruit extracts of Sida tiagii were investigated for
      it's hypoglycemic and antioxidant potential in neonatal streptozotocin-induced
      (type 2) diabetic rats. Grinded fruits were extracted with 90% ethanol and
      partitioned with n-hexane (n-hexane extract; HS) and ethyl acetate (Ethyl Acetate
      Extract; EAS) successively. The residual ethanol fraction (residual ethanol
      extract; RES) was dried on water bath separately. All three extracts were
      administered orally at a dose of 200 mg/kg and 500 mg/kg. Blood glucose level,
      cholesterol, GSH (glutathione), elevated thiobarbituric acid-reactive substances
      (TBARS), glycated hemoglobin and liver glycogen contents were measured after 19
      days treatment. The residual ethanol extract of Sida tiagii fruits significantly
      improve glycemic parameter and showed antioxidant activity in diabetic rats. The
      results of the present study indicated that the active fraction of Sida tiagii
      (i.e., RES) is suitable for development of a promising phytomedicine for the
      treatment of diabetes mellitus.

PMID- 22876614
TI  - Platelet aggregation and anti-inflammatory effects of garden pea, Desi chickpea
      and Kabuli chickpea.
AB  - Inflammation is the natural body defense mechanism for the removal of injurious
      agents, necrosed cells and tissues from the body. This study was aimed to
      evaluate the anti-inflammatory and platelet aggregation effects of three
      medicinal plants of Pakistan. Methanolic extract of garden pea inhibited
      arachidonic acid (AA)-induced platelet aggregation (IC50 = 35 microg/mL) and
      platelet activating factor (PAF)-induced platelet aggregation (IC50 = 38
      microg/mL) in a dose dependent fashion. Methanolic extract of Desi chickpea
      inhibited arachidonic acid (AA) induced platelet aggregation (IC50 value = AA =
      46 microg/mL) in dose dependent fashion while was found not active against PAF
      induced platelet aggregation. Methanolic extract of Kabuli chickpea was found not
      active against both arachidonic acid (AA)-induced platelet aggregation and PAF
      induced platelet aggregation. The best potential to inhibit in vitro COX-2
      activity showed garden pea (Pisum sativum: the synthesis of PGE2 reduced by 92%
      in comparison with untreated control wells) followed by Desi chickpea (Cicer
      arietinum var; 87% inhibition) and Kabuli chickpea extracts (Cicer arietinum var:
      65% inhibition). All extracts were tested at concentration 20 microg/mL. in COX-2
      assay. The results indicate that if the same were happening in vito, Garden pea,
      Desi chickpea and Kabuli chickpea could be useful as natural antithrombotic anti
      inflammatory materials.

PMID- 22876615
TI  - Development and characterization of self emulsifying drug delivery system of a
      poorly water soluble drug using natural oil.
AB  - Objective of present study involves preparation and evaluation of self
      emulsifying drug delivery system (SEDDS) of ibuprofen using peanut oil. SEDDS
      were composed of varying concentrations of peanut oil (solvent), tween 80
      (surfactant) and span 20 (co-surfactant). Influence of concentration of
      surfactant/co-surfactant and globule size on dissolution rate was investigated.
      Dissolution rate was studied in phosphate buffer pH 6.8 using dissolution
      apparatus II. The dissolution rate of self emulsifying capsule was found to be
      significantly faster than that from conventional tablet. The optimized SEDDS
      released approximately above 85% of ibuprofen within 30 min, while conventional
      ibuprofen tablet could released only 36% in 30 min. Therefore, these SEDDS could
      be a better alternative to conventional drug delivery system of ibuprofen.

PMID- 22876616
TI  - Effect of hydroxypropyl-beta-cyclodextrin on the solubility, stability and in
      vitro release of ciprofloxacin for ocular drug delivery.
AB  - Eye drops in the form of an aqueous solution with a lower viscosity are preferred
      for local administrations in ophthalmology. In ophthalmic formulations,
      cyclodextrins (CDs) are frequently used in recent years in order to increase
      water solubility, stability and bioavailability of an active substance and
      decrease an irritation to the eye. The scope of the present study was to
      investigate the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the
      solubility, stability and in vitro release of ciprofloxacin (CIP). According to
      the phase solubility studies, A(L) type solubility curve was obtained. HPCD
      improved the solubility of CIP 3 times at pH 5.5 and 2 times at pH 7.4. The two
      month stability studies indicated that CIP was more stable at pH 5.5 than at pH
      7.4 and the stability of CIP was significantly increased by HPCD. The stability
      constant of the HPCD:CIP complex was increased further by a-ddition of 0.1% (w/v)
      polymer (HPMC and PVP) to the aqueous medium including HPCD. Stability constant
      of solutions prepared in an ultrasonic water bath was higher than solutions
      prepared by heating in an autoclave. The results indicated that the CIP:HPCD
      complex increased in vitro release of CIP and the addition of polymer promoted
      this increase even more.

PMID- 22876617
TI  - Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization
      of sustained release mucoadhesive matrix tablets of domperidone.
AB  - The objective of this study was to extend the GI residence time of the dosage
      form and to control the release of domperidone using directly compressible
      sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite
      design (CCD) was employed to study the influence of independent variables like
      gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2)
      on dependent variable like mucoadhesive strength, tensile strength, release
      exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and
      rel(18 h) (release after 18 h). Tablets were prepared by direct compression
      technology and evaluated for tablet parametric test (drug assay, diameter,
      thickness, hardness and tensile strength), mucoadhesive strength (using texture
      analyzer) and in vitro drug release studies. The tensile strength and
      mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/-
      0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9),
      respectively. The release kinetics follows first order and Hixson Crowell
      equation indicating drug release following combination of diffusion and erosion.
      The n varies between 0.834 and 1.273, indicating release mechanism shifts from
      non fickian (anomalous release) to super case II, which depict that drug follows
      multiple drug release mechanism. The t50 time was found to increase from 5 +/-
      0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with
      increasing concentration of both polymers concluding with release controlling
      potential of polymers. The accelerated stability studies were performed on
      optimized formulation as per ICH guideline and the result showed that there was
      no significant change in tensile strength, mucoadhesive strength and drug assay.

PMID- 22876618
TI  - Development and optimization of formulation for treatment of copper deficiency in
      human organism.
AB  - The aim of this study was to design and optimize a new tablet formulation for
      treatment of copper deficiency in human organism by using an experimental design.
      The new no-veneered tablets, prepared by a wet granulation technique, are
      containg active substance, a copper(II) complex with polysaccharide pullulan. The
      binder concentration, the disintegrant concentration and the resistance to
      crushing were used as independent variables in the formulation, while in vitro
      measured drug release characteristics of the tablets was response variable in a
      full factorial design 2(3) modeling. A cubic model for data fitted was used to
      examine the obtained results. They showed that the resistance to crushing has the
      most significant effect on copper(II) complex release from the formulation, while
      the disintegrant concentration has smaller influence on dissolution profile of
      copper(II) complex and the binder concentration had minor impact in this study.
      Lower value of resistance to crushing has influence on better dissolution
      profile. Furthermore, physical characteristics of the tablets were evaluated,
      viz., drug content, hardness, thickness, friability, disintegration time, mass
      variation, particle size and size distribution.

PMID- 22876619
TI  - Preparation and statistical optimization of alginate based stomach specific
      floating microcapsules of simvastatin.
AB  - The present study involves preparation and characterization of floating
      microcapsules with simvastatin as model drug for prolongation of gastric
      residence time. The main objective is to improve solubility of simvastatin beta
      CD complex (1:2) by co-precipitation method and then to deliver the same in
      sustained release dosage form. Sustained-release simvastatin microcapsules were
      prepared by the ionic gelation technique, using carbopol 941 as swellable
      floating polymer. A 3(3) full factorial design was used to study the effect of
      polymer concentration, drug complex and sodium alginate by plotting main effect
      plot and 3D surface plots. The formed microcapsules were subjected to various
      evaluation tests such as drug encapsulation efficiency, in vitro drug release and
      surface morphology by scanning electron microscopy. Powdered X-ray diffractometry
      and FTIR were used to investigate the complexation of simvastatin in the
      microcapsules. As the carbopol 941 is self swellable polymer, immediate floating
      was observed. The in vitro release studies and floating behavior were performed
      in HCI buffer of pH 1.2. The release profile and dissolution kinetic showed that
      drug release from the microcapsules follows zero order kinetics. It was concluded
      from the present investigation that porous carbopol 941 microcapsules are
      promising sustained release system as well as stomach specific carriers for
      delivery of simvastatin.

PMID- 22876620
TI  - 3D-QSAR studies of some tetrasubstituted pyrazoles as COX-II inhibitors.
AB  - Pharmacophore mapping studies were undertaken for a series of molecules belonging
      to tetrasubstituted pyrazoles as canine COX-II inhibitors. A six point
      pharmacophore with 3 hydrogen bond acceptors (A), one hydrophobic group (H) and
      two aromatic rings (R) as pharmacophoric feature was developed. The
      pharmacophoric hypothesis yielded a statistically significant 3D-QSAR model, with
      a correlation coefficient of r2 = 0.958. The developed pharmacophore model was
      externally validated by predicting the activity of test set molecules. The
      squared predictive correlation coefficient of 0.852 was observed between
      experimental and predicted activity values of test set molecules. The geometry
      and features of pharmacophore model describe the key structure-activity
      relationship of COX-II inhibitors, can predict their activities, and can thus be
      used to design novel inhibitors.

PMID- 22876621
TI  - Determinants of NSAID choice in rheumatoid arthritis--a drug utilization study.
AB  - Long term nonsteroidal anti-inflammatory drug (NSAID) medication is associated
      with gastrointestinal (GI) adverse events. This paper aimed to depict main
      determinants of NSAID drug choice (GI safe/traditional NSAIDs) in a rheumatoid
      arthritis (RA) patient sample (n=143). According to our logistic regression
      model, current/prior GI adverse events in the anamnesis was the only significant
      determinant of GI safer NSAID use (OR 3.1, p = 0.01). There was significant
      difference regarding most NSAIDs between the RA study sample and the total
      Hungarian population, suggesting that chronic administration could also influence
      the NSAID choice. GI safe NSAIDs were much preferred in the RA study sample than
      in the total population. In conclusion, the NSAID medication of the observed 143
      patients was considered to be reasonable regarding both cardiovascular and GI
      safety.

PMID- 22876622
TI  - Legislative and non-legislative regulations concerning Rx drug advertisement in
      the European Union and the United States--comparative analysis.
AB  - Drug advertising is one of the most popular forms of communication between
      pharmaceutical companies and prospect drug purchasers. In the face of strong
      competition on the pharmaceutical market on the one hand, and patient's high
      susceptibility to various forms of advertising on the other, drug producers try
      to reach as wide group of recipients as possible. However, proper medicine use
      requires not only doctor's wide knowledge and experience, but also patient's
      awareness of necessity of rational drug usage. Advertising activities related to
      this group of medicines are covered by rigorous law regulations, with taking into
      account above-mentioned issues, and other specific features of drugs available
      with prescription. The aim of this article is to present legislative and non
      legislative regulations concerning Rx drugs, taking into consideration law
      regulations that are in force in the European Union and the United States. Ethic
      codes implemented by drug producers associations were also used.

PMID- 22876624
TI  - [Non-clostridial anaerobic bacteria can cause acute pyelonephritis (an
      experimental trial)].
AB  - Acute obstructive pyelonephritis (PN) caused by Peptococcus niger (Pn), E. coli
      and mixed infection (Pn + E. coli) was modeled in rabbits. Morphologic
      examination showed that in animals with peptococcal infection renal lesions were
      identical to those in escherichial PN. Hemorrhagic infarctions and vasculitis
      develop in animals with mixed infection. These morphological findings were
      confirmed bacteriologically. The experimental trial confirms the role of Pn in
      development of acute obstructive PN in animals.

PMID- 22876623
TI  - [Choice of antibacterial drugs in urinary infection].
AB  - A rise in efficacy of the treatment of acute infection affecting the lower
      urinary tract (LUTI) and prolongation of recurrence-free interval in chronic LUTI
      can be achieved only by an optimal antibacterial treatment. The study was made of
      987 community-acquired strains of uropathogens from the patients living in 20
      cities of the Russian Federation, Belarus and Kazakhstan (of them, 903 strains
      were from Russia). Enterobacteriaceae comprised 83.5%. E. coli infection of LUTI
      was found in 63.5% patients. The incidence of this infection was about the same
      both in uncomplicated and complicated cases (64.6 and 62.1%, respectively). Most
      active oral drugs against E.coli were phosphomycin (98.4%), furasidin (95.7%),
      nitrofurantoin (94.1%) and oralcefalosporins of the third generation (ceftibuten
      and cefixim). As to Enterobacteriaceae, only phosphomycin had activity against
      these bacteria above 90%, i.e. 91.5%. Furasidin and nitrofurantoin activity was
      86.3 and 76.8%, respectively. From parenteral drugs, most active against E. coli
      were carbapenems (ertapenem, meropenem, imipenem. Strains resistant to them were
      not isolated. High in vitro activity was demonstrated also by
      cefoperason/sulbactam (97.4%), piperacillin/tasobactam (95.7%), cefalosporins of
      the third/fourth generation and amikacin (98.9%). Carbapenems were also highly
      active against Enterobacteroaceae. Empiric treatment of uncomplicated urinary
      infection should be performed with medicines which are not used for other
      indications.

PMID- 22876625
TI  - [X-ray phase analysis of stag-horn concrements in citizens of south Russia].
AB  - It is known that recurrent nephroliths form in about half of the operated
      patients within 5 years after operation while 60% of all recurrences occur 3
      years after removal of the primary concrement. To prevent recurrent nephroliths,
      it is important not only to detect metabolic disturbances but also to investigate
      chemical composition of uroliths. Mineral composition of 112 stag-horn
      concrements from patients living in the south of Russia was studied with x-ray
      phase analysis which showed that 62.9% concrements had mixed composition.
      Compared to patients with primary stag-horn nephrolithiasis, patients with
      recurrent one more often had calcium-phosphate and calcium-oxalate concrements
      than urate concrements. Chemical composition of the concrements depended on
      features of the relief of the region where the patients live. Newly established
      mineral characteristics of stag-horn concrements in the citizens of south Russia
      should be taken into consideration both in surgical treatment and follow-up of
      such patients.

PMID- 22876626
TI  - [Effects of low-frequency magnetic field on urolith solubility in vitro].
AB  - A 27% increase in solubility of urolith substance was observed in water
      pretreated with alternating magnetic field (22 Hz, 25 mT) for 60 min compared to
      untreated water. Changed density of distilled water without concrement in
      response to the impact of alternating magnetic field does not influence
      qualitatively on solubility of urolith substance in the urolith placement in the
      pretreated water. Shift in wave length of maximums in spectra of solution
      absorption evidences for more intensive solution of organic components of
      uroliths in water pretreated with alternating magnetic field than in untreated
      water.

PMID- 22876627
TI  - [Use of isolated intestinal segments in surgical treatment of radiation-induced
      lesions of the urinary tract].
AB  - Fifteen females with various radiation-induced lesions of the urinary tract
      (urinary fistulas alone or in combination with uni- or bilateral ureteral
      strictures) received surgical treatment using isolated intestinal segments. The
      above surgical intervention reestablished natural urination in 9 patients. They
      were relieved from continuous urine leakage into the vagina and/or from
      nephrostomas. Heterotopic urine derivation was performed in 6 patients. Thus,
      restoration of natural urination in most patients with postradiation lesions can
      be performed only in usage of isolated intestinal segments. In some cases
      heterotopic urine derivation is indicated.

PMID- 22876628
TI  - [Estimation of the risk and prevention of postoperative esophagogastroduodenal
      hemorrhage in elderly urological patients].
AB  - Open transvesical adenomectomy was made in 853 old males with prostatic adenoma
      in Samara Hospital for Veterans from 1995 to 2010. The age of the patients ranged
      from 60 to 89 years, of them 389 (45.6%) were from 60 to 75 years of age, 464
      (54.4%) - 75 to 89 years. Elective simultaneous operations were conducted in 104
      (12.2%) of the above patients. It is shown that early postoperative
      esophagogastroduodenal hemorrhage after adenomectomy occurs in 7% old patients.
      Endoscopic parietal pH-metry is "a gold standard" in selective sensitive
      diagnosis of acid-dependent conditions in presenile and senile patients with
      prostatic adenoma. The proposed method of prediction of the risk of early
      postoperative esophagogastroduodenal hemorrhage provides realization of the
      principle of a differential approach to effective prevention of the hemorrhage in
      old patients with prostatic adenoma. Complex preoperative preparation using
      adequate antisecretory therapy in old patients with prostatic adenoma with the
      risk of early postoperative esophagogastroduodenal hemorrhage decreases
      hemorrhage rate from 7 to 0.4%. Prevention of early postoperative
      esophagogastroduodenal hemorrhage in old patients with prostatic adenoma should
      become as obligatory as prevention of cardiovascular, thromboembolic, pulmonary
      and pyoseptic complications.

PMID- 22876629
TI  - [Preoperative correction of antihypertensive treatment in urological inpatients
      comorbid with arterial hypertension].
AB  - We studied preoperative correction of antihypertensive treatment in patients with
      urogenital diseases. The results of the study showed necessity of arterial
      pressure normalization in such patients especially before extracorporeal
      lithotripsy. Choice of hypotensive drugs after nephrectomy is specified.

PMID- 22876630
TI  - [Pilot experience in using adjustable suburethral sling in the treatment of
      anatomic stress urinary incontinence in females].
AB  - Adjustable suburethral prolen sling (Agency for Medical Innovations) was set up
      during surgery via transobturatory approach in 21 females with stress urinary
      incontinence (SUI). Mean age of the patients was 58.5 years (32-76 years). Only 3
      (14%) women failed to retain urine on postoperative day 1, the other 18 of 21
      (86%) women no longer showed SUI. Obstructive urination was observed in 4 of 21
      (19%) patients, residual urine was present in 3 of these 4 patients (120, 170 and
      220 ml). Correction of the sling position was made in early postoperative period
      in 7 (33.3%) patients. Under local anesthesia of the paraurethral channels with
      0.5% novocain solution, the sling was displaced in the direction from the urethra
      to obturatory opening in 3 women with residuary SUI, from the urethra to the
      vagina - in 4 women. After regulation of the sling position all the patients
      retained urine and had no residual urine after urination. Thus, the suburethral
      prolen sling the position of which can be adjusted in early postoperative period
      is an effective method of treating females with anatomic SUI.

PMID- 22876631
TI  - [The role of human papilloma virus in development of chronic urethritis and
      vulvodynia in females: perspectives of immunomodulating therapy].
AB  - The article is devoted to combined affection of the lower urinary tracts and
      genitalia in women with human papilloma virus (HPV) infection which manifests
      with persistent recurrent urethritis, pelvic pain syndrome. The colposcopic and
      urethrocystoscopic features, disturbed microcirculation of urethral and vaginal
      mucosa in virus infection promoting recurrences and persistence of HPV are
      discussed. Immunomodulators (inosin pranobex-groprinosin) are recommended for
      more effective treatment.

PMID- 22876632
TI  - [Treatment of chronic prostatitis in prophylaxis of prostatic adenoma].
AB  - The results of a retrospective study of efficacy of prostamol uno in a standard
      single dose of 320 mg/day in prevention of chronic prostatitis recurrences and
      prostatic adenoma used for 5 years as an adjuvant to standard therapy of chronic
      prostatitis exacerbations were compared with those of standard course
      antibacterial and anti-inflammatory treatment alone. The analysis demonstrated
      that prostamol uno (Serenoa repens extract) in a dose 320 mg/day improves both
      subjective symptoms (data of IPSS, QoL scale) and objective ones (the absence of
      the disease progression and adverse effects, enhancement of the erectile
      function). Prostamol uno is effective for prevention of both recurrences of
      chronic prostatitis exacerbations and development of prostatic adenoma.

PMID- 22876633
TI  - [Prostagut forte treatment of patients with prostatic adenoma with comorbid
      chronic prostatitis].
AB  - The study consisting of four visits included 69 patients with prostatic adenoma
      and concomitant chronic prostatitis. The patients received either monotherapy
      with an alpha adrenoblocker or combined treatment including phytodrug prostagut
      forte. The results of the study showed that the above combined treatment produces
      more pronounced and persistent improvement of urodynamic indices, leads to
      reduction of leukocyte count in the urine and prostatic secretion, upgrades
      quality of life. The absence of side effects allows recommendation of prostagut
      forte for treatment of presenile and senile patients with prostatic adenoma and
      associated pathology.

PMID- 22876634
TI  - [Diagnosis and treatment of chronic urogenital trichomoniasis in males].
AB  - The article presents the results of laboratory, clinical and device diagnosis of
      chronic urogenital trichomoniasis. Case reports show efficacy of this disease
      treatment with combined drug safocid.

PMID- 22876635
TI  - [Treatment of patients of local colorectal cancer with involvement of the urinary
      organs: participation of the urologist].
AB  - We treated 314 patients with local colorectal cancer (LCRC). Of them, 189 (60.2%)
      were males, 125 (39.8%)--females, age from 31 to 79 years (mean age 59.6 +/- 5.7
      years). Combined surgery with resection of the affected urinary system components
      en bloc was made in 277 (88.2%) patients. Palliative urological care for
      obstructive lesions of the urinary system was delivered to 37 (11.8%) patients.
      Surgical intervention was performed by a surgical team consisting of
      coloproctologists and urologist. Treatment of most of the patients was
      multimodal. As a result, it became clear that involvement of the urinary system
      in tumor process in LCRC patients must not entail rejection of combined surgery.
      Subtotal resection of the urinary bladder affected by a tumor in LCRC patients is
      functionally valid and oncologically radical. Efficacy of this intervention is
      confirmed by a satisfactory social adaptation--18 (51.4%) of 35 followed up
      patients resumed their jobs. Resection of different parts of the urinary system
      has insignificant impact on postoperative lethality. Palliative urological care
      in urinary obstruction in LCRC patients improves quality of life and efficacy of
      conventional treatment. Treatment of such severe patients should be conducted
      with participation of the urologist who decides on optimal methods of urinary
      derivation, performs surgical reconstruction and follow-up of the patients after
      the operation.

PMID- 22876636
TI  - [Prostatic cancer in males living in the Khabarovsk, Komsomolsk-on-Amur and
      Khabarovsk region].
AB  - In 2004-2008 the Khabarovsk Region was considered as a territory of an increased
      risk for prostate cancer with the incidence rate of 22.2 +/- 1.6 per 100000
      males. The epidemiologic situation in Khabarovsk city corresponded to an average
      incidence rate registered in the Khabarovsk Region (20.5 +/- 2.3 per 100000 males
      in 2004-2008). A prostate cancer incidence rate in Komsomolsk-on-Amur city was
      1.9 times higher than in Khabarovsk city. An impact of an occupational factor on
      the risk of prostate cancer in males working in Komsomolsk-on-Amur industry was
      found.

PMID- 22876637
TI  - [Pilot experience of percutaneous nephrolithotripsy in dorsal positioning of the
      patient].
AB  - Percutaneous nephrolithotripsy (PNLT) is widely used in surgical treatment of
      nephrolithiasis. The patient's body position in this operation is, as a rule,
      prone. However, this position is often uncomfortable or even impossible for
      patients with obesity, bone diseases and deformations which sometimes occur in
      pulmonary, cardiovascular and other diseases. The aim of our study was to see how
      dorsal positioning of the patient during PNLT influences the results of this
      surgery. A total of 109 patients after PNLT for concrements of the upper urinary
      tract entered the study. They were divided into two groups: operated in the
      dorsal position (n = 46, 42.2% - the study group) and operated in the standard
      prone position (n = 63, 57.8%--the control group). The patients were matched by
      gender, age, size and location of the concrements, surgical procedure. Residual
      concrements were detected in 9(19.5%) patients of the study group, 7 of them were
      reoperated (PNLT, ureterolithotripsy, extracorporeal lithotripsy) while in the
      control group residual concrements were in 10 (14.9%) patients, 7 of them (10.4%)
      were reoperated. Thus, complete concrements evacuation from the upper urinary
      tract was achieved in 80.5 and 85.1%, respectively. Mean duration of the
      operation was 66.4 and 72.6 min, respectively; mean bed occupancy was 9.3 and 9.1
      day, respectively. Complications in both groups consisted for the most part of
      postoperative hematuria and exacerbation ofpyelonephritis. No injuries of the
      adjacent organs were registered. Thus, PNLT in dorsal position is an effective
      and safe treatment of nephrolithiasis, especially in patients with obesity, bone
      lesions and severe concomitant diseases.

PMID- 22876638
TI  - [Transurethral resection in physiological salt solution].
AB  - The analysis is given of the technique, tolerance, clinical efficacy, safety,
      results of transurethral resection in physiological salt solution (TRPSS)
      performed in 788 patients from August, 2005 to November, 2010 for different
      diseases of the lower urinary tract and prostatic gland. TRPSS made it possible
      to operate patients whom transurethral resection was contraindicated, for
      example, those with a pacemaker, to reduce a complications rate, for instance,
      the obturator nerve reflex. Irrigation with isotonic salt solution prevents
      dilution hyponatriemia and TUR-syndrome thus increasing safe time of the
      resection for maximal removal of the tissue.

PMID- 22876639
TI  - [A contact electroimpulse impact on the ureteral and bladder wall of mature dogs:
      a 1-year results of a morphological prospective study].
AB  - The aim of the study was investigation of morphological changes in the urinary
      bladder and ureteral wall of dogs in response to contact electroimpulse impact
      (CEII); to develop recommendations for utilization of contact electroimpulse
      lithotripsy in humans. Effects of single-impulse CEII on the bladder and ureteral
      mucosa produced by an electroimpulse lithotripter were studied in 23 mature
      mongrel dogs. The morphological material was studied immediately after the
      impact, 1, 6, 14 days and 1, 3, 6 and 12 months after it. The 0.1-0.7 J
      electroimpulse impact resulted in fragmentary epithelial necrosis and aceptic
      inflammation within a muscular layer. An enhanced to 0.8 J impact caused local
      damage to all layers of the wall including adventitium while a 0.9-1 J impact
      caused ureteral perforation in 3 cases. Duration of morphological rehabilitation
      depended on the impact power and was optimal for 0.1-0.5 J impulses with complete
      mucosal repair to day 14 and complete morphological rehabilitation to month 6
      after the procedure. In power 0.6-1 J mucosal recovery increased to 1 month while
      complete formation of the connective tissue finished after 1 year. None cases of
      development of ureteral strictures after CEII was observed in follow-up for 1
      year.

PMID- 22876640
TI  - [Preputial reconstruction in surgical correction of distal hypospadia in
      children].
AB  - Treatment for distal hypospadia was conducted in 148 children aged from 11 months
      to 14 years admitted to the urological department of the Syktyvkar Central
      Children's Hospital in 1998-2010. Operation MAGPI was made in 12 (8.8%) children,
      TIP--in 87 (61.8%), Mathieu--in 15 (11.0%), displacing urethroplasty--in 25
      (18.4%). Preputial reconstruction was performed in 29 (21%) children: in 21 in
      displacing urethroplasty and in 8 in conduction of TIP operation. The number of
      complications in displacing urethroplasty and TIP is less than in MAGPI and
      Mathieu operations. Significantly less number of complications was seen only in
      comparison of TIP with MAGPI. Operations with preputial reconstruction had no
      such complications as urethral fistula, meatostenosis and separation of the glans
      penis. Two cases of partial preputial separation after the operation were
      observed. Thus, preputial reconstruction can be conducted in most children with
      distal hypospadia, the risk of postoperative complications being the same.

PMID- 22876641
TI  - [Conservative hemostasis after injury of the iliac vein during non-standard
      ureteroscopy].

PMID- 22876642
TI  - [Biometric ranging of the corpses destroyed at the site of a catastrophe in terms
      of gender, longitudinal and circumferencial dimensions, and the degree of
      subcutaneous fat distribution].
AB  - The quantitative criteria for biometric ranging of destroyed corpses in terms of
      anatomical localization, gender, longitudinal length, trunk circumference, and
      the folds of subcutaneous fat are proposed. The wealth of anthropometric
      materials obtained in the studies of various Caucasoid populations was used to
      calculate the normative tables for biometric ranging of the decomposed corpses.
      The proposed technology excludes the subjective assessments for the purpose of
      such classification at the sites of catastrophes. Moreover, it promotes the
      accumulation of the variety of valuable information, such as the size of the
      collar, headwear, and footwear, clothing size and height, and portrait features,
      that can be used for victim identification.

PMID- 22876643
TI  - [Studies of dentition abnormalities in children of the Republic of Armenia for
      the purpose of personality identification].
AB  - This paper reports the results of investigations carried out to elucidate the
      frequency and the structure of various forms of abnormalities of dentition among
      the children of the preschool and school age in the Republic of Armenia. These
      data may be of help for the forensic medical personality identification
      especially for the expertise of unrecognized corpses. Moreover, these data
      provide an indirect picture of the prevalence of abnormalities of dentition among
      the adult population of the country. Specifically they may sometimes be used to
      identify the ethnic and/or racial background of a person.

PMID- 22876644
TI  - [On the stability of the irritant dibenz-[b,f]-[1,4]-oxazepine (substance CR)].
AB  - The objective of the present study was to determine the duration and conditions
      of persistence of the irritant dibenz-[b,f]-[1,4]-oxazepine (substance CR) on the
      environmental objects. The quantitative analysis of the substance on cotton
      fabric specimens was carried out using the approved method of high performance
      liquid chromatography (HPLC) with UV detection at different time periods and
      envirobmental conditions. It was shown that the main factor determining the
      lifetime of dibenz-[b,f]-[1,4]-oxazepine on the cotton fabric is the ambient
      conditions. By way of example, the "open" and "closed", storage of such specimens
      during 300 days resulted in the decrease of the amount of substance CR to 22.5
      and 79% of the initial level respectively. By the end experiment (day 600) these
      values lowered to 3 and 52.5% respectively. Taken together, the results of the
      study indicate that dibenz-[b,f]-[1,4]-oxazepine can be described as a substance
      resistant to environmental impacts. It is comparable in terms of stability with
      such known irritants as capsicum oleoresin and pelargonic acid morpholide.

PMID- 22876645
TI  - [Forensic medical assessment of the mechanisms of development of gunshot lesions
      caused by elastic destructive agents].
AB  - This paper reports the results of analysis of the data obtained in experimental
      studies and practical expert assessments of body injuries inflicted by rubber
      balls for traumatic weapons. The causes accounting for the polymorphism of such
      injuries and the mechanisms of their development were elucidated by means of
      damage simulation taking into consideration the physical and dynamic properties
      of elastic ball-type destructive agents and the morphological structure of
      different anatomical regions of the human body. The results of the study may be
      of interest for differential diagnostics of gunshot lesions caused by elastic
      destructive agents.

PMID- 22876646
TI  - [Classification of bone injuries inflicted by the teeth of the carnivorous
      animals].
AB  - The morphological characteristics of a variety of bone injuries inflicted by the
      teeth of the carnivorous animals are presented. The results of their analysis
      provided a basis for the morphological classification of such traumas taking into
      consideration the current views of the mechanisms underlying the process of their
      formation.

PMID- 22876647
TI  - [Age-related changes in the nervous apparatus of the blood vessels in the brain
      and spinal cord].
AB  - This work was designed to study changes in the nervous apparatus of the blood
      vessels in the brain and spinal cord with a view to developing methods for the
      determination of the biological age in man. Pial and intramedullary vascular
      systems of the brain and spinal cord were examined in different periods of
      postnatal ontogenesis (between the age of 1 and 90 years) using histological,
      fluorescent-histochemical, and immunohistochemical methods as well as by ink
      injections into the blood vessels, scanning and transmission electron microscopy.
      The data obtained on the age-related rearrangement of the nervous apparatus of
      the arterial vessels in the brain and spinal cord have not only theoretical
      significance but can also be used for the solution of practical problems
      encountered in the practical work of forensic medical experts.

PMID- 22876648
TI  - [The method for expert assessment as a tool for the improvement of the
      methodological basis of the activities of a bureau of forensic medical
      expertise].
AB  - An important aspect of the problem of iatrogenic poisoning is the lack of
      comprehensive relevant information. Many experts employed at the bureaus of
      forensic medical expertise believe that this problem can be resolved only based
      on a multifaceted approach. The results of questionnaire studies and cause-and
      effect analysis allowed the following recommendations to be proposed for
      addressing the problem under consideration: making a minimal list of equipments
      necessary to maintain activities of forensic medical departments, updating the
      list of toxic substances to be studied in the laboratories of bureaus of forensic
      medical expertise, modification of the reporting form No 42 to be filled by such
      bureaus. The optimal approach is thought to be the equipment of all bureaus in
      compliance with the universal requirements, introduction of standard methods and
      technologies for the analysis of the materials included in the list of toxic
      substances to be determined.

PMID- 22876649
TI  - [Chemical toxicological identification of esfenvalerate].
AB  - The optimal conditions for the isolation of esfenvalerate from the biological
      specimens have been determined. It was shown that this compound can be separated
      from the endogenous component of a biological material by means of liquid-liquid
      extraction and chromatography on a L 40/100 mcm silica gel column. The
      identification and quantitative analysis of esfenvalerate extracted from
      cadaveric liver and blood can be accomplished with the use of thin layer
      chromatography, UV and IR spectrophotometry as well as chromatomass spectrometry.

PMID- 22876650
TI  - [Forensic medical expertise of delayed consequences of traffic accidents included
      in article 6.11 of the Medical Criteria].
AB  - The medical documentation pertaining to 767 victims of traffic accidents was
      revised. These subjects were classified in the acute post-traumatic period as
      experiencing serious harm to health in terms of the qualifying sign "substantial
      persistent loss of at least of one third of general working ability" (SPLGWA)
      based on the results of primary examination. It was shown that in the course of
      therapeutic and rehabilitative treatment of the subjects with bone fractures
      listed in articles 6.11.1, 6.11.2, 6.11.4 to 6.11.10 of the Medical Criteria most
      of the patients have their compromised functions repaired up to complete recovery
      of the working ability. According to the repeated evaluation the substantial
      (35%) loss of the working ability persisted only in 25.8% of the victims. 56.7%
      of the victims were estimated to have lost 10-30% of their working ability;
      SPLGWA was absent in 17.5% of the examined subjects.

PMID- 22876651
TI  - [Histomorphological features of gunshot injuries to the calvarian bone in
      nephrogenic osteopathy].
AB  - This histological study of calvarian bones with the injuries inflicted by a shot
      from an Osa traumatic non-lethal pistol revealed nephrogenic osteopathy in the
      preceding period. The pathologically altered bone tissue was damaged by a
      relatively mild tangential traumatic impact. It is concluded that the possibility
      of such pathological changes should be taken into consideration in the forensic
      medical expertise of any trauma including gunshot injuries.

PMID- 22876652
TI  - [Atypical location of an organ as a cause of medical errors].

PMID- 22876653
TI  - [The theory of postmortem rigidity: the history and an original concept].
AB  - The original theory of postmortem rigidity has been developed and substantiated
      based on the concept of postmortem muscular contracture. It is postulated that
      the unrestricted growth of Ca2+ concentration in myoplasm of contractile cells
      during the immediate postmortal period brings the actin-myosine complex to the
      force generation state without subsequent relaxation.

PMID- 22876654
TI  - [The current potential of forensic medical expertise of a local radiation
      injury].
AB  - The present review concerns radiation injury, a most challenging problem facing
      modern forensic medical expertise. It is shown that its successful solution
      requires the combined application of all currently available relevant methods
      including radio- and biodosimetry, forensic histological examination, etc.

PMID- 22876655
TI  - [The scoring and rating system for the estimation of the teaching efficiency in
      forensic medicine].
AB  - The authors developed a system of criteria for the evaluation of the results of
      education of forensic medical students based on the scoring and rating scale. The
      major requirements for the organization of academic activities are considered. It
      is emphasized that the compliance with these requirements is an indispensable
      prerequisite for the introduction of the above system in the training routine at
      the Department of Forensic Medicine.

PMID- 22876656
TI  - [Vladimir Ivanovich Shtol'ts].

PMID- 22876657
TI  - [Laparoscopic adrenalectomy for isolated metastasis of adrenal glands].
AB  - OBJECTIVES: The treatment of adrenal metastases using laparoscopic surgery still
      remains a matter of considerable controversy. The aim of this study is to present
      our experience of laparoscopic adrenalectomy for isolated adrenal metastasis.
      METHODS: From June 2004 to June 2011, 5 adults (4 males/1 female) with isolated
      metastases to the adrenal glands underwent laparoscopic adrenalectomy. These
      patients included 3 cases of lung carcinoma, a case of hepatocellular carcinoma,
      and a case of renal cell carcinoma. The median patient age was 69 (range 61 to
      72), and the median tumor size was 3.5 cm (range 2.5 to 7.0). RESULTS:
      Laparoscopic adrenalectomies were performed without any complications using
      transperitoneal and retroperitoneal approaches. The median operative time was 142
      minutes (range 126 to 174), and the estimated blood loss was 38 ml (range 25 to
      158). The resection margins were free in all cases. A patient with lung cancer
      has been treated with adjuvant chemotherapy, otherwise, 4 patients have not.
      Regarding the oncological outcome, 3 of 5 patients were alive without any
      recurrence at a median follow-up of 14 months. About the rest two cases, one was
      alive with lung metastasis occurred at 15 months later, the other was died of the
      cancer at 14 months later. CONCLUSIONS: Laparoscopic adrenalectomy for isolated
      adrenal metastasis is thought to be feasible. However, the indication of the
      surgery must be determined depending on tumor size, cancer characteristics, risk
      factors and so on. Additionally, the operative procedures such as approaches must
      be discussed sufficiently.

PMID- 22876658
TI  - [Validation of 2009 TNM classification based on a prognostic analysis of 350
      patients treated for renal cell carcinoma].
AB  - PURPOSE: To validate 2009 TNM classification (7th edition) of renal cell
      carcinoma (RCC), we reevaluated our RCC database depends on 6th and 7th TNM
      staging and analyzed a prognostic divergence between subgroups. METHODS: A study
      population of 350 patients with RCC was retrospectively reviewed based on the TNM
      classification both 6th and 7th editions. Cause-specific survival (CSS) in each
      group was estimated using Kaplan-Meier method. RESULTS: Applying the new TNM
      system, 336 patients were divided into pT1a 131, pT1b 105, pT2a 31, pT2b 13, pT3
      a 38, pT3b 3, pT3c 0, pT4 14. Previously pT3b-staged 11 cases with renal vein
      involvement without vena caval extension were included into pT3a. Due to the
      positive direct invasion into the adrenal gland, previously pT3-staged six
      patients were changed to pT4. Kaplan-Meier curves revealed no significant
      differences in CSS between each a/b subgroups from pT1 to pT3. Particularly, no
      significant statistical value was recognized between pT2a and pT2b subgroups.
      Patients with direct adrenal invasion tended to show a less favorable prognosis
      than those with invasion beyond Gerota. CONCLUSIONS: (1) pT2 subdivision does not
      affect prognostic value. (2) Population imbalance is enhanced due to the pT 3
      reclassification. (3) Direct adrenal invasion is compatible with pT4 category.

PMID- 22876659
TI  - [Rehabilitation for intravaginal ejaculatory dysfunction with using a
      masturbation aid].
AB  - OBJECTIVES: Recently the incidence of intravaginal ejaculatory dysfunction is
      increasing among infertile couples in Japan. Some unusual ways of masturbation
      and psychogenic issues were reported to cause this disorder. Patients, who had
      done masturbation in an unusual way for long time since their adolescence, were
      difficult to gain normal intravaginal ejaculation by the behavior therapy which
      was used for erectile dysfunction. We, therefore, used a masturbation aid (TENGA)
      for rehabilitation of ejaculation to overcome this condition. PATIENTS AND
      METHODS: From January, 2010 through March, 2011, a total of 16 patients with
      intravaginal ejaculatory dysfunction underwent rehabilitation of ejaculation
      using TENGA. Patients' satisfaction and achievement of intravaginal ejaculation
      were evaluated by the questionnaire. RESULTS: Twelve patients (75%) could
      ejaculate in the masturbation aid (TENGA). Five patients (31%) succeeded to
      ejaculate in the partner's vagina after rehabilitation. CONCLUSIONS: A
      masturbation aid (TENGA) was a useful tool to correct the way of masturbation and
      achieve normal intravaginal ejaculation. This masturbation aid can be one of the
      effective options for the treatment of intravaginal ejaculatory dysfunction.

PMID- 22876660
TI  - [The current clinical status of kidney cancers in patients with the VHL disease
      in Japan: a nationwide epidemiological survey].
AB  - PURPOSE: To understand the current clinical features of kidney cancers in
      patients with von Hippel-Lindau (VHL) disease in Japan. SUBJECT AND RESULT: We
      performed a nationwide epidemiological survey of patients with VHL disease using
      the epidemiology program for incurable disease by the Ministry of Health, Labour
      and Welfare. The content of the survey included age of onset of VHL disease, sex,
      residential area, treatment modalities, kidney function, ECOG performance status,
      and prognosis. Here, we report the results of kidney cancer. The incidence rate
      of kidney cancer in VHL disease in Japan is 50.3% (206/409). Males and females
      are equally affected. The mean age of onset is 37.8 + 0.92 years. The median age
      of onset is 35 years. The ages of onset are distributed between 15 and 75 years.
      The mostly affected age of onset is between 20 and 50 years. The incidence rate
      of patients with metastasis is 11.1% (23/206). The most common site for
      metastasis is the lung (60%, 14/23). Due to multiple numbers of tumors at initial
      diagnosis and the metachronous development of tumors, patients received treatment
      on multiple occasions (mean 1.6 times), including partial nephrectomy (46%),
      total nephrectomy (31%) or radiofrequency ablation (14%) up to 6 times. The
      multiple treatments resulted in deterioration of the kidney function, causing
      chronic dialyses in 7 cases (3%). The ECOG performance status was scored as more
      than 1 in 42% of patients. The ten-year survival rate in VHL patients with kidney
      cancer was 94%, which is relatively high compared with that survival rates in
      sporadic kidney cancers. CONCLUSION: The current study indicates that the age of
      onset of kidney cancers in VHL disease is relatively young, and kidney cancers
      have features of metachronous development. The clinical features of kidney cancer
      developed in VHL disease among Japanese population are very similar with those in
      European countries. Multiple treatments result in deterioration of the kidney
      function.

PMID- 22876661
TI  - [Clinical status of Von Hippel-Lindau disease associated pheochromocytoma in
      Japan: a national epidemiologic survey].
AB  - PURPOSE: To understand the current clinical status of pheochromocytoma (Pheo) in
      patients with von Hippel-Lindau disease (VHL) in Japan. PATIENTS AND METHODS: We
      picked up and summarized Pheos from a nationwide epidemiologic survey for VHL
      disease based on the epidemiologic study program for incurable disease by the
      Japanese Ministry of Health, Labour and Welfare. The details of the survey
      included age of onset, sex, living area, treatment modalities, functional status
      of the adrenal gland after surgical treatment, and patient outcome. RESULTS: The
      incidence rate of Pheo in VHL disease in Japan was 15.1% (62/409). Males and
      females were equally affected. The mean and median ages of onset were 29.7 and
      31.5 years, respectively. The age of onset was distributed between 10 and 75
      years and presented two large peaks between 15-20 and 35-40 years. Twenty-six
      (41.9%) bilateral cases, 8 (12.9%) paragangliomas, and 4 (6.4%) malignant cases
      were found. Forty-one (65%) patients underwent surgical resection once and 13
      (9%) underwent 2 or 3 times surgeries whereas six (10%) nonfunctional cases were
      surveyed without surgical treatment. Fourteen of 26 bilateral Pheos (56%)
      received steroid replacement therapy following surgery. Four cases died from
      metastases of malignant Pheos and one from a severe infection during steroid
      replacement therapy. None of the patients died of cardiovascular complication due
      to Pheo crisis. CONCLUSION: It is concluded that Pheos in VHL disease developed
      from a relatively young age and was associated with 15% of all patients,
      including a small ratio of malignant cases. More than 40% of cases suffered
      bilateral adrenal tumors. The clinical features in Japan appear to be similar to
      those in the Western countries according to the current survey.

PMID- 22876662
TI  - [Renal tuberculosis in an isthmus of a horseshoe kidney after bacillus Calmette
      Guerin therapy for bladder cancer].
AB  - A 63-year-old man with a horse shoe kidney was evaluated after an episode of
      asymptomatic gross hematuria. Cystoscopy revealed bladder tumor near the right
      ureteral orifice, and transurethral resection demonstrated high grade pT1
      urothelial carcinoma. The patient was started on intravesical BCG instillation
      therapy at a dose of 81 mg weekly for 8 weeks without fever. 6 months later after
      the final BCG treatment, CT examination demonstrated a renal hypovascular tumor
      in an isthmus of a horseshoe kidney. We couldn't deny malignant tumor and
      tumorectomy was performed. Histological examination revealed epithelioid cell
      granulomas and no organisms were identified by Ziehl-Neelsen or Grocott-Gomori
      stains for acid-fast bacilli and fungi. We reported a rare case of renal
      tuberculosis in an isthmus of a horseshoe kidney after BCG therapy for bladder
      cancer that was considered due to vesicoureteral reflux.

PMID- 22876663
TI  - [A case of mesothelial cyst at the inguinal region].
AB  - A 54-year-old man presented with the left inguinal swelling. The operation was
      performed with diagnosis of the hydrocele of spermatic cord. A tumor was 3.0 cm x
      2.5 cm in size, cystic with yellowish serous fluid. After the operation, this
      tumor is diagnosed as mesothelial cyst through the histopathologic examination.
      This is a rare case, however it is worth to consider that there is a possibility
      to be a mesothelial cyst when the tumor has been found at the inguinal region.

PMID- 22876664
TI  - [A case of true ureteral diverticulum on functional solitary kidney].
AB  - A 13-year-old girl presented with an occult blood in urine. CT revealed right
      rudimentary kidney and left hydronephrosis. Renogram demonstrated right poor
      renal function pattern and left obstructive pattern. She underwent left
      pyeloplasty. Histologic examination revealed the true ureteral diverticulum. True
      ureteral diverticulum is a rare congenital anomaly and synonymous with blind
      ending bifid ureter. This is a sixth case in the Japanese literature.

PMID- 22876665
TI  - [Solitary fibrous tumor of the adrenal gland with renal cell carcinoma and
      angiomyolipoma at the same time; a case report].
AB  - Solitary fibrous tumor (SFT) is a neoplasm of pleura and its occurrence in the
      retroperitoneal space is rare. We report a case of SFT of the adrenal gland
      associated with ipsilateral renal cell carcinoma (RCC) and angiomyolipoma (AML).
      A 48-year-old woman was referred to our hospital for a left renal AML. Computed
      tomography (CT) in our hospital showed a left adrenal mass (25 x 20 mm). Because
      the adrenal tumor was nonfunctioning, she was followed at outpatient clinic. Four
      years later, CT showed an increase in the left adrenal tumor size (42 x 30 mm)
      and a left RCC. Left adrenectomy and partial nephrectomy for RCC and AML were
      simultaneously performed. Histological examination revealed adrenal SFT and clear
      cell carcinoma and AML of the kidney. We present a brief review on histological
      characteristics of retroperitoneal SFT and its occurrence in the adrenal grand
      region.

PMID- 22876666
TI  - [Long survival in patient with invasive renal pelvic carcinoma treated with
      frequentative resection of pulmonary metastasis and chemotherapy: a case report].
AB  - A 51-year-old man was referred to our hospital for treatment of left renal pelvic
      tumor diagnosed with computed tomography (CT) on health screening.
      Retroperitoneoscopy-assisted radical left nephroureterectomy was performed under
      a diagnosis of left renal pelvic carcinoma. Histopathological examination showed
      urothelial carcinoma (UC), Grade 2 > > Grade 3, pT3. Subsequently to the radical
      operation, pulmonary metastasis appeared four times. But the patient with free of
      recurrence survives 6 years later, treated with chemotherapy and resection of
      pulmonary metastasis. Although the patient with high grade invasive renal pelvic
      carcinoma usually has a poor prognosis, it seems to be a possibility that if the
      lesion is resectable, resection of pulmonary metastasis carries a good prognosis.

PMID- 22876667
TI  - [Response of isozyme and stress indexes of Coptis chinensis to UV-B radiation].
AB  - OBJECTIVE: To study the physiological mechanism of anti-stress of Coptic
      chinensis and provide theoretical basis for its cultivation and promoting its
      quality. METHODS: Different degrees of the range of time and intensity of UV-B
      radiation were set in the experiment. Used the technique of polyacrylamide
      gelatin vertical board electrophoresis (PAGE) to analyse the isozyme and related
      stress index. RESULTS: The isoenzymic bands of SOD1 (Rf = 0.125), SOD2 (Rf =
      0.312), CAT1 (Rf = 0.428), POD3 (Rf = 0.290), POD4 (Rf = 0.636) were induced by
      UV-B radiation after 3 hours, with the increase of the time of UV-B radiation,
      those isoenzymic bands was going to vanish or became unclear. Moreover,
      isoenzymic bands of CAT1 (Rf = 0.428), POD3 (Rf = 0.290) disappeared in advance
      under heavy intensity of UV-B radiation. Furthermore, the contents of MDA,
      soluble sugar, proline were higher dramatically than those of control group under
      UV-B radiation. However, excluding the increases of proline in UL group, the
      content of MDA, soluble sugar, proline of other groups commenced to decrease
      slowly and isoenzymic bands of soluble protein increase after 7 hours of UV-B
      radiation. CONCLUSION: The increase of the expression of antioxidase isozyme,
      accumulation of soluble sugar, soluble protein and other antioxidase matter is
      induced by the short-time UV-B radiation, which can protect Coptis chinensis from
      being harmed by UV-B radiation. However, regulation system of Coptis chinensis
      are broken, metabolism is disordered, the bands of antioxidase isozyme vanish or
      weaken, the bands of soluble protein are increased and widened, these phenomenon
      is caused by 7 hours of UV-B radiation.

PMID- 22876668
TI  - [Photosynthetic characteristics of Drynaria fortunei and its relation to
      environmental factors].
AB  - OBJECTIVE: To have a better utilization of diurnal photosynthetic variation of
      Drynaria fortunei in three light environments and provide theoretical basis for
      its artificial cultivation. METHODS: Diurnal photosynthetic variation of Drynaria
      fortunei were determinated by portable photosynthesis analysis system (Li-6400),
      and correlation between physiological and environmental factors was further
      analysed. RESULTS: The diurnal net photosynthetic rate (NPR) exhibited a single
      peak curve, with the peak value of NPR occurring at 15:30. The mean diurnal Pn of
      D. fortunei in three environments followed a tread of tree epiphytes > shine >
      shade. WUE had significantly positive correlation with NPR. Air temperature (Ta),
      ambient CO2 concentration (Ca) and relative humidity (RH) were the main
      environmental factors for NPR of D. fortunei. CONCLUSION: The optimum cultivation
      condition of D. fortunei is 32 degrees C, RH around 40%, and appropriate shade is
      recommended.

PMID- 22876669
TI  - [Study on germination characteristic of seed of Dendranthema indicum].
AB  - OBJECTIVE: To find out the optimum condition for the germination of seed of
      Dendranthema indicum by studying the effects of pretreatment,phytohormone and
      temperature on it, and offer the basis for its standardized culture. METHODS: The
      seed purity, weight per 1000 seeds, seed moisture content and seed viability were
      determined. The germination of D. indicum seed was tested under following
      conditions: pretreatment (acid, base, warm water, boiling water), phytohormone
      (IBA, 6-BA, NAA) and treatments under different temperature (10, 20, 25, 30
      degrees C). RESULTS: The seed purity was 99.4%; The weight per 1000 seeds was
      0.2941 g; The seed moisture content was 4.39%; The seed viability was 85.3%; The
      tests of pretreatment couldnt increase the germination of D. indicum seed;
      Phytohormone had limited effect on the germination of the seed; Temperature
      condition showed significant effects on the germination. CONCLUSION: The optimum
      condition for the germination of the seed of D. indicum is 25 degrees C on filter
      paper.

PMID- 22876670
TI  - [Analysis of liposoluble constituents in Holotrichia diomphalia by GC-MS and
      investigation their anti-inflammatory and analgesic activities].
AB  - OBJECTIVE: To analysis liposoluble constituents of Holotrichia diomphalia by GC
      MS and measure their anti-inflammatory and analgesic activities. METHODS: The
      composition of liposoluble constituents were determined by GC-MS. The
      dimethylbenzene-induced mice inflammatory models were established. The pain
      models were obtained by hot plate and acetic acid in mice. RESULTS: Twenty-two
      components were identified from the petroleum ether extract of Holotrichia
      diomphalia. The major components were oleic acid, palmitic acid and palmitoleic
      acid. The petroleum ether extract was able to significantly inhibit the mice ear
      edema induced by dimethyl-benzene. The pain in mice caused by acetic acid and hot
      plate were evidently suppressed by the petroleum ether extract. CONCLUSION: The
      petroleum ether extract of Holotrichia diomphalia has obvious anti-inflammation
      and analgesic effects.

PMID- 22876671
TI  - [Compare the composition and content of Arnebiae radix and the stem residues].
AB  - OBJECTIVE: To compare the composition and content of Arnebiae Radix and the stem
      residues. METHODS: TLC and HPLC were used to identify Arnebia, ultraviolet
      visible spectrophotometry was used to determine the content of hydroxy
      naphthoquinone total pigment in Arnebia, HPLC was used to determine the total
      content of /3-P'-dimethyl acrylamide Aka Ning and shikonin. RESULTS: The number
      of spots of Arnebia Radix was consistent with that of the stem residues in 10
      batches of medicinal materials, the former was larger and deeper in color. Their
      features of fingerprint are the same,at the same retention time,the peak area of
      radix was larger; The average content of hydroxy naphthoquinone total pigment was
      3.631% in the radix, and 1.516% in the stem. The total content of beta-beta'
      dimethyl acrylamide Aka Ning and shikonin in the radix and the stem were
      respectively 0.89% and 0.309%. CONCLUSION: The ingredients in the radix and the
      stem residues are the same, but the contents of root of the total pigment content
      of hydroxyl-naphthoquinone, beta-beta'-dimethyl acrylamide Aka Ning and shikonin
      are twice higher than those of the stem residues.

PMID- 22876672
TI  - [Determination of six heavy metal elements in Zanthoxylum nitidum in twelve
      habitats of guangxi by ICP-AES].
AB  - OBJECTIVE: To determine the contents of six heavy metal elements in traditional
      Chinese medicine of Zanthoxylum nitidum in twelve habitats by ICP-AES. METHODS:
      Nitric acid- perchloric acid mixed acid digested system was used to completely
      decomposed the organic compounds effectually. The As, Cr, Hg, Ni, Cd and Pb were
      determined by the absorption spectroscopy under set up working conditions.
      RESULTS: An efficient, simple and accurate method was established. The recoveries
      were 90.82%-101.21% and RSDs were within 3.0%. CONCLUSION: The contents of six
      heavy metal elements are different in Zanthoxylum nitidum from different
      habitats. As, Cr and Hg were not detected. The content of Pb which from eleven
      habitats is consistent with the standards of medicine and export except from
      Nanning habitats, meanwhile the content of Cd all exceeds those standards.

PMID- 22876673
TI  - [New processing procedure for Croton tiglium with study on comparison of Croton
      tiglium and processed product].
AB  - OBJECTIVE: To build a new processing procedure for Croton tiglium, providing a
      more simple, efficient and safe way of processing. METHODS: Used the contents of
      isoguanosine and toxic protein in Croton tiglium as the indexes to investigate
      the effect of different temperature, thickness and baked time on processing for
      Croton tiglium. After established all factors and levels, processed a batch of
      Croton tiglium under optimum processing conditions and compared it with raw
      Croton tiglium in the test of acute toxicity and gastrointestinal propulsive
      motility. RESULTS: The parameters of optimum processing were as follows:the
      temperature was set at 180 degrees C, the thickness of placement was 3 cm and
      baked time was 90 min. The LD50 value of raw Croton tiglium and the processed
      Croton tiglium was 888 mg/kg and 2139 mg/kg respectively. CONCLUSION: The
      processing procedure is simple, affordable, safe and efficient, deserved to
      promote for application.

PMID- 22876674
TI  - [Study on HPCE fingerprint of Eucommiae Cortex].
AB  - OBJECTIVE: To establish the analytical method for the fingerprint of Eucommiae
      Cortex by HPCE and compare the fingerprints of Eucommiae Cortex and its processed
      products. METHODS: Based on the mode of high performance capillary
      electrophoresis, 60 mmol/L sodium borate-20 mmol/L sodium dihydrogen phosphate
      10% methanol (pH 10.0) was used as buffer solution. The separation voltage was 20
      kV and the detection wavelength was set at 210 nm. Pinoresinol diglucoside was
      used as a reference standard, the chromatographic fingerprint were determined.
      The data were analyzed by fuzzy cluster and fingerprint similarity evaluation
      softwarewas used to compare the similarity of samples. RESULTS: HPCE fingerprints
      with 10 common peaks of Eucommiae Cortex were established preliminarily. It was
      discovered that a small number of samples differed from others. Regarding to the
      fingerprints of Eucommiae Cortex and its processed products, there were obvious
      differences in the relative areas of common peaks. CONCLUSION: The method is
      reliable, accurate and can be used for quality control of Eucommiae Cortex.

PMID- 22876675
TI  - [Study on HPLC fingerprint of Herba Lysimachiae].
AB  - OBJECTIVE: To establish the chromatographic fingerprint for Herba Lysimachiae by
      RP-HPLC. METHODS: The sample solutions were prepared by extracting material with
      boiling water,followed by extracting with BuOH from the aqueous extract and
      analyzed by RP-HPLC with a Phenomenex C18 column (4.6 mm x 150 mm, 5 microm),
      gradiently eluted with A (acetonitrile containing 0.5% of acetic acid)-B (water
      containing 0.5% of acetic acid) at 30 degrees C, and monitored with UV detector
      at 255 nm. The flow rate was 1.0 mL/min, and sample volume injected was 20
      microL. The chromatograms of different batches of Herba Lysimachiae were compared
      by the software of Similarity Evaluation System for Chromatographic Fingerprint
      of TCM (Version 2004A). RESULTS: HPLC Fingerprint of Herba Lysimachiae was
      established with Rutin as the reference compound. 13 common peaks were selected
      as the fingerprint peaks of Herba Lysimachiae. CONCLUSION: The established HPLC
      fingerprint of Herba Lysimachiae has desirable precision, reproducibility, and
      can be applied to routine quality control of Herba Lysimachiae.

PMID- 22876676
TI  - [Identification characters of leaf morphological and venation pattern of
      Baphicacanthus cusia with its confused herb Clerodendrum cyrtophyllum].
AB  - OBJECTIVE: To study the identification characters of Baphicacanthus cusia and its
      confused herb Clerodendrum cyrtophyllum and establish an identification method.
      METHODS: LMVP (leaf morphological-venation pattern for identification Chinese
      herbs) and QAERM (quantitatively analyze and evaluate reliability for the method
      of identification Chinese herbs) were applied for the study. RESULTS: The main
      differences of the leaf were as follows: Baphicacanthus cusia: leaf base
      attenuate, dry leaves deep dull blue green, spindle spots, no or small glandular
      scales somewhere, the limit between midrib and petiole was not clear, below
      undermost secondary vein some tertiary veins issue from midrib; Clerodendrum
      cyrtophyllum: leaf base not attenuate; dry leaves yellow green, green, green
      yellow, yellow brown, no spindle spots, densely covered by glandular scales,the
      limit between midrib and petiole was clear, below undermost secondary vein none
      tertiary veins issue from midrib. With the mentioned six groups of key
      differences, the both plants could be successfully identified from each other.
      The accuracy of identification results (AC) was from 98.5% to 99.2%, the
      repeatability of identification results: agreement rate for observation (ARO) was
      97.7% and Kappa value was 0.95. CONCLUSION: The established method is simple,
      rapid, economic and reliable.

PMID- 22876677
TI  - [Chemical constituents from the fruits of Kadsura marmorata].
AB  - OBJECTIVE: To study the chemical constituents from the fruits of Kadsura
      marmorata. METHODS: The chemical constituents were isolated and purified by
      chromatography on silica gel, Sephadex LH-20 column and HPLC. RESULTS: 9
      compounds were isolated and identified as 4,5-dihydroxy-3-methoxybiphenyl (I),
      eriobofuran (II), 3beta, 16beta-dihydroxy urs-2-ene (III), 2alpha, 3beta, 6beta,
      23-tetrahydroxy urs-12,18-dien-28-oic acid (IV), 2alpha,3beta,23-trihydroxy urs
      12-en-28-oic acid (V), rutin (VI), 2-ethylhexanoic acid (VII), 2-monolaurin
      (VIII), glyceryl monoricinoleate (IX) on the basis of NMR and EI-MS spectroscopic
      analysis. CONCLUSION: All these compounds are isolated from this genus for the
      first time.

PMID- 22876678
TI  - [Chemical constituents from the fruits of Areca catechu].
AB  - OBJECTIVE: To investigate the chemical constituents of the fruits of Areca
      catechu. METHODS: The chemical constituents were isolated by silica gel, RP-18
      and Sephadex LH-20 column chromatographies. Their structures were determined by
      chemical and spectroscopic methods. RESULTS: Thirteen compounds were isolated
      from the 95% ethanol extract of the fruits of Areca catechu. Their structures
      were identified as isorhamnetin (1), quercetin (2), liquiritigenin (3), 5,7,4'
      trihydroxy-3',5'-dimethoxyflavanone (4), (+)-catechin (5), resveratrol (6),
      ferulic acid (7), vanillic acid (8), 5,8-epidioxiergosta-6,22-dien-3beta-ol (9),
      stigmasta-4-en-3-one (10), beta-sitosterol (11), cycloartenol (12), and de-O
      methyllasiodiplodin (13), respectively. CONCLUSION: Compounds 2-4,6,7,9,10, 12,13
      are isolated from this plant for the first time.

PMID- 22876679
TI  - [Study on the chemical constituent from the dichloromethane extract. of the pine
      needles of Cedrus deodara].
AB  - OBJECTIVE: To study the chemical constituents of the dichloromethane extracted
      from pine needles of Cedrus deodara. METHODS: Compounds were isolated and
      purified from the dichloromethane extract of pine needles by chromatography on
      silica gel and Sephadex LH-20. Their structures were identified on the basis of
      spectroscopic analysis and physicochemical property. RESULTS: Nine compounds were
      isolated and purified. Their structures were identified as stigmasterol (1),
      oleanolic acid (2), parahydroxybenzaldehyde (3), beta-sitosterol (4),
      syringaresinol (5), daucosterol (6), p-hydroxybenzoic acid (7), gallicin (8) and
      gallic acid (9). CONCLUSION: Compounds 1-3, 5 -9 are isolated from pine needles
      of this genus for the first time.

PMID- 22876680
TI  - A new cytotoxic dinaphthofuran-7,12-dione derivatives from the seeds of Impatiens
      balsamina.
AB  - OBJECTIVE: To study the chemical constituents of seeds of Impatiens balsamina.
      METHODS: The chemical constituents of the plant were isolated and purified by
      column chromatography and their structures were elucidated on the basis of
      physicochemical properties and spectral date. RESULTS: A new dinaphthofuran-7,12
      dione derivative, named balsaminone C(1), with another two known dinaphthofuran
      7,12-dione derivatives, balsaminone A (2), balsaminone B (3) were isolated.
      CONCLUSION: Compound 1 is a new compound. These compounds exhibit cytotoxicity
      against cancer cell lines A549, Bel-7402 and Hela. Compound 1 is worth to be
      further studied as potential anticancer agent.

PMID- 22876681
TI  - [Study on the effects of different compatibility of guizhi decoction on component
      of volatile oil from Cinnamomum cassia by GC-MS].
AB  - OBJECTIVE: To study the changes of volatile oil from different compatibility of
      Guizhi decoction and explore their connection. METHODS: The volatile oil of
      Cinnamomum cassia and different compatibility of Guizhi decoction extracted by
      steam distillation were analyzed by GC-MS. RESULTS: The main components of
      volatile oil in Cinnamomum cassia were found in different compatibility of Guizhi
      decoction and they accounted the most amount of total volatile oil,but the
      contents of the main components were decreased, there were more components
      existed in different compatibility of Guizhi decoction than those in Cinnamomum
      cassia, the new components came from Zingiber officinale mostly. CONCLUSION: GC
      MS can be used to reflect the changes of volatile oil from different
      compatibility of Guizhi decoction, and the result will provide some evidence for
      the research of regular pattern of compatibility in Guizhi decoction.

PMID- 22876682
TI  - [GC-MS analysis of chemical constituents of essential oil from Callicarpa
      kwangtungensis and their antimicrobial activity].
AB  - OBJECTIVE: To analyze the chemical constituents of the essential oil from
      Callicarpa kwangtungensis and investigate their antimicrobial activity in vitro.
      METHODS: The essential oil of Callicarpa kwangtungensis were extracted by steam
      distillaton. The chemical constituents were separated and analyzed by GC-MS.
      Their relative percentages were calculated with peak area normalization method.
      RESULTS: 38 compounds were identified, accounting for 76.01% of the peak area of
      the total ion-current chromatogram. The essential oil had different antimicrobial
      activities. CONCLUSION: The main constituent of the essential oil is terpenoids
      (59.25%), and showing different activities against Staphylococcus aureus,
      Escherichia coli and Candida albicans.

PMID- 22876683
TI  - [Effects of total flavonoids in Drynaria fortunei on osteoblasts differentiation
      and the expression of ERK1/2 and p38 MAPK after treatment by high glucose in
      vitro].
AB  - OBJECTIVE: To observe the effects of Total Flavonoids in Drynaria fortunei (TFDF)
      on osteoblasts differentiation activity after treatment by high glucose and
      observe the effects on p38MAPK and ERK1/2 signaling protein in osteoblasts.
      METHODS: Primary osteoblasts of newborn SD rats was extracted and cultured and
      its biological characteristics was observed. MTT method was used to observe
      osteoblasts' cytotoxicity,and to choose a suitable concentration of TFDF in the
      culture medium. pNPP,ELISA,Alizarin dyeing were used to test ALP,Type I
      collagen,osteocalcin and mineralization of osteoblasts after treatment by
      different concentration of glucose respectively and after treatment by TFDF and
      high glucose. Western-blot was used to detect p38MAPK and ERK1/2 protein
      phosphorylation after treatment by TFDF and high glucose. RESULTS: Primary
      osteoblasts of newborn SD rats could be used well in this experiment. According
      to the toxicity of TFDF on OB, 25, 50, 100 mg/L of TFDF were selected for the
      experimental concentration gradient. ALP, Type I collagen,osteocalcin and
      mineralization of osteoblasts after treatment with glucose (25, 50 mmol/L) were
      less than those of control group respectively. TFDF could increase ALP, Type I
      collagen, osteocalcin activity and mineralization of osteoblasts in a dose
      dependent manner after treatment by high glucose (25 mmol/L). TFDF(50 mg/L) could
      increase protein phosphorylation of p38MAPK and ERK1/2 of osteoblasts after
      treatment by high glucose (25 mmol/L). CONCLUSION: High glucose can decrease
      differentiation and mineralization of osteoblasts. TFDF can increase
      differentiation and mineralization of osteoblasts in a dose-dependent manner
      after treatment by high glucose. The role of TFDF in the promotion of osteoblasts
      differentiation is related to protein phosphorylation of p38MAPK and ERK1/2.

PMID- 22876684
TI  - [Study on the pharmacokinetics of ginkgolide B for injection in rats].
AB  - OBJECTIVE: To study the pharmacokinetics of ginkgolide B for injection in rats.
      METHODS: The serum concentration of ginkgolide B was determined by LC-MS and
      calculate its parameter of pharmacokinetics via DAS2.0 software. RESULTS: After
      intravenous of 0.75, 3.75 and 14.0 mg/kg ginkgolide B, parameters of
      pharmacokinetics of ginkgolide B were: Tmax were all (0.083 +/- 0) h, Cmax were
      (422.312 +/- 14.203), (1608.467 +/- 226.677), (1987.036 +/- 237.202) microg/L,
      AUC0-1 were (533.833 +/- 114.943), (1786.029 +/- 137.066), (1943.44 +/- 415.892)
      microg x h/L. CONCLUSION: Ginkgolide B has three compartment model in rats.

PMID- 22876685
TI  - [Experimental study of extract from Prunella vulgaris inducing B, T lymphoma cell
      apoptosis].
AB  - OBJECTIVE: To investigate the effects of extract from Prunella vulgaris on
      proliferation of human B lymphoma cell line Raji cells anf T lymphoma cell line
      Jurkat cells and discuss the mechanism. METHODS: Used different concentrations of
      extract from Prunella vulgaris to treat Raji and Jurkat cells and collected cells
      after 48 h respectively, the proliferation inhibition rate, the DNA Ladder and
      the apoptosis rate of Raji and Jurkat cells were examined by MTT assay, agarose
      gel electrophoresis and flow cytometry respectively; Western blot was used to
      detect the change of BCL-2, BAX protein. RESULTS: Different concentrations of the
      extract from Prunella vulgaris could inhibit the proliferation of both Raji and
      Jurkat cells remarkably (P < 0.01), the IC50 of Raji cells, 18.01 +/- 0.92
      microg/mL, was lower than that of Jurkat, the difference was significant
      statistically (P < 0.05); Apoptosis related DNA Ladder appeared after treated
      Raji and Jurkat cells with the extract from Prunella vulgaris; Compared with the
      control group, with the increase of the concentration of the extract from
      Prunella vulgaris, the early cell apoptosis rate of Raji and Jurkat were all
      increased,the early cell apoptosis rate of the extract from Prunella vulgaris of
      15, 20 and 25 microg/mL treated Raji and Jurkat cells were (9.46 +/- 0.25)%,
      (21.68 +/- 0.46)%, (35.03 +/- 0.35)% and (4.06 +/- 0.14)%, (13.59 +/- 0.23)%,
      (22.92 +/- 0.20)% respectively. With the same concentration, the early apoptosis
      rate of Raji cells was higher than that of Jurkat cells significantly (P < 0.01);
      Compared with the control group, with the in- crease of the concentration of the
      extract from Prunella vulgaris, the expression of BCL-2 protein was down
      regulated and BAX up-regulated, With the same concentration, the decline degree
      of BCL-2 protein expression and the increase degree of BAX protein expression in
      Raji cells was more remarkable than that in Jurkat cells, the difference was
      significant (P < 0.05). CONCLUSION: The extract from Prunella vulgaris can
      inhibit the proliferation of lymphoma cells and the inhibition is realized by
      inducing apoptosis, the mechanism of inducing cell apoptosis with extract from
      Prunella vulgaris is probably related with the BAX and BCL-2 protein expression,
      the inhibition effect on Raji cells is greater than that of Jurkat cells.

PMID- 22876686
TI  - [Study on anti-proliferation activity and the mechanisms of alkaloid monomers
      from Gelsemium elegans on HepG2 cell in vitro].
AB  - OBJECTIVE: To investigate the effects of alkaloid monomers from Gelsemium elegans
      on proliferation of HepG2 cell in vitro and the possible mechanism. METHODS: MTT
      assay was used to measure the inhibitory of three alkaloid monomers on HepG2 cell
      in vitro. The most effective fraction was chosen to test whether the effect was
      in time-and dose-dependent manner. The morphological changes were observed by the
      light microscope and the cell cycle alteration through the flow cytometric assay.
      The activity of Caspase-3, Caspase-8 and Caspase-9 were detected by a Caspases
      colorimetric assay kit. RESULTS: The results showed that koumine, Gelsemine and
      Gelsenicine could significantly inhibit the proliferation of HepG2 cell and
      Gelsenicine, the most effective fraction, was clearly in dose- and time-dependent
      manners, while exhibited low cytotoxicity to the Vero cell. The cell treated with
      Gelsenicine for 48 h showed distinctive morphological changes. The cells treated
      with 200 and 400 microg/mL shrinked and fell off from the bottom. At the same
      time, the cells were arrested at S phase and the apoptosis increased apparently.
      The activity of Caspase-3, Caspase-8 and Caspase-9 was increased in a dose
      dependent manner. CONCLUSION: Three alkaloid monomers from Gelsemium elegans,
      especially Gelsenicine, could inhibit proliferation of HepG2 cell obviously. The
      mechanism may be related to cell cycle arrest and activation of Caspase-3,
      Caspase 8 and Caspase-9.

PMID- 22876687
TI  - [Effects of resveratrol on apoptosis and ROS production in Hepa 1-6
      hepatocarcinoma cells].
AB  - OBJECTIVE: To observe the effects of resveratrol on apoptosis and ROS production
      in murine hepatocarcinoma Hepa 1-6 cells in vitro. METHODS: Hepa 1-6 cells were
      treated with different dose of resveratrol (20 micromol/L, 40 micromol/L, 80
      micromol/L). Cell proliferation was detected with MTT assay at 24 h, 48 h and 72
      h. Hoechst 33258 staining was used to visualize apoptotic morphology. Cell
      apoptosis was detected by flow cytometry analysis. Activated caspase-3 was
      detected by western blot. Intracellular ROS production was observed by 2',7'
      dichlorofluorescin diacetate (DCF-DA) staining. RESULTS: Compared with the
      control, upon treatment with 20-80 micromol/L resveratrol for 24 h, 48 h or 72 h,
      the proliferation of Hepa 1-6 cells was significantly inhibited in a time-dose
      dependent manner. 20-80 micromol/L resveratrol also induced apoptosis and
      apoptotic morphology change in Hepa 1-6 cells accompanied with caspase-3
      activation and ROS generation. CONCLUSION: Resveratrol could inhibit cell
      proliferation, induce apoptosis in murine hepatocarcinoma Hepa 1-6 cells, and the
      mechanism may associated with caspase-3 activation and ROS production.

PMID- 22876688
TI  - [Research on the preparative method of Arctigenin].
AB  - OBJECTIVE: To research on the preparation of Arctigenin in vitro. METHODS: Took
      enzyme concentration, time course and substrate concentration as investigation
      factors, used Box-Behnken design-response surface methodology to optimize the
      enzyme hydrolysis path of Arctigenin. RESULTS: The best operational path for
      Arctigenin was as follows: the temperature was 50 degrees C, pH was 4.8, enzyme
      concentration was 0.44 U/mL, time course was 46.81 min, substrate concentration
      was 0.29 mg/mL, the conversion rate was 90.94%. CONCLUSION: This research can be
      regarded as a referencein preparing Arctigenin in vitro.

PMID- 22876689
TI  - [Extraction technology optimization and quality analysis of volatile oil in
      Rhizoma Curcumae].
AB  - OBJECTIVE: To investigate the effect of technologies and conditions on volatile
      oil yield extracted from Rhizoma Curcumae. METHODS: Water Extraction coupling
      Rectification (WER) and Steam Distillation (SD) technologies were applied to
      extract the volatile oils based on orthogonal table L9 (3(3)) to find out
      optimized condition. RESULTS: Variance and range analysis of orthogonal
      experiment results showed that the best conditions of WER and SD were as follows:
      ultrasound 0 h, extract 12 h with 8 (or 12 fold water for SD) fold water amount.
      Paired T test on the yields of the oils indicated that the oil yields prepared by
      WER and SD were significantly different. GC-MS analysis characterized 12 common
      compounds,which occupied 97.19% (SD) and 92.25% (WER) of the ones identified,
      respectively. Moreover, the relative percentage of the common constituents were
      almost the same. CONCLUSION: Ultrasound is not good for extracting volatile oil
      from Rhizoma Curcumae. WER could not only increase the oil yield of Rhizoma
      Curcumae, but also keep the quality of the oils accord with that extracted by SD.

PMID- 22876690
TI  - [Study on the extraction technology and hypoglycemic activity of lectin from
      Trichosanthes kirilowi].
AB  - OBJECTIVE: To extract lectins from Trichosanthes kirilowi and study their
      hypoglycemic activity. METHODS: The optimal extraction process included the
      following parameters were conformed by optimization analysis,lectins extracted
      from Trichosanthes kirilowi was achieved by ammonium sulfate precipitation; The
      agglutinate activity was determined by using the agglutination test with 5% human
      blood cells. Human hepatocarcinoma cell HepG2 and the alloxan-induced diabetic
      mice model were used to assess hypoglycemic activity of Lectin in Trichosanthes
      kirilowi. RESULTS: The agglutination indexes of lectins extraction buffer were
      32; The cell and mice tests indicated that the lectins exhibited hypoglycemic
      activity in the 70% saturation. CONCLUSION: The optimum extraction technology is
      as follows: extraction with PBS, the material-water ratio is 1:30, the extraction
      time is 24 h, while the concentration of sodium chloride is 0 mol/L and pH is
      7.2. Precipitate lectins by ammonium sulfate in the 70% saturation, centrifugal
      speed is 10 000 tracted from Trichosanthes kirilowi exposes proper hypoglycemic
      activity.

PMID- 22876691
TI  - [Optimization for supercritical CO2 extraction with response surface methodology
      of Prunus armeniaca oil].
AB  - OBJECTIVE: To optimize the extraction conditions of Prunus armeniaca oil by
      Supercritical CO2 extraction and identify its components by GC-MS. METHODS:
      Optimized of SFE-CO extraction by response surface methodology and used GC-MS to
      analysis Prunus armeniaca oil compounds. RESULTS: Established the model of an
      equation for the extraction rate of Prunus armeniaca oil by supercritical CO2
      extraction, and the optimal parameters for the supercritical CO2 extraction
      determined by the equation were: the extraction pressure was 27 MPa, temperature
      was 39 degrees C, the extraction rate of Prunus armeniaca oil was 44.5%. 16 main
      compounds of Prunus armeniaca oil extracted by supercritical CO2 were identified
      by GC-MS, unsaturated fatty acids were 92.6%. CONCLUSION: This process is simple,
      and can be used for the extraction of Prunus armeniaca oil.

PMID- 22876693
TI  - The future of medicine in Tennessee: is it the road to utopia or the road to
      serfdom?

PMID- 22876692
TI  - [Effects of "attenuation and synergia" for Bushenhuoxue Granules on Parkinson's
      patients].
AB  - OBJECTIVE: To study the effects of "Attenuation and Synergia" for Bushenhuoxue
      Granules (BSHXG) on Parkinson's patients. METHODS: 120 patients were enrolled and
      divided into two groups randomly, the control group were treated with placebo and
      treatment group with BSHXG, both groups based on Madopar treatment. Double
      blinded clinical trial was adopted in treatment period. Follow-up period for 6
      months. Usage of Madopar and score of treatment complications were adopted to
      measure related motor complications before and after treatment. RESULTS: Usage of
      Madopar and score of treatment complications in treatment group were decreased (P
      < 0.05). No adverse effects were found in this trial. CONCLUSION: BSHXG can
      decrease the side-effects of Madopar and put off the development of PD. The
      effects of "Attenuation and Synergia" of BSHXG becomes clear with time.

PMID- 22876694
TI  - The times, they are a-changin'.

PMID- 22876695
TI  - Dr. Robinson: still "practicing" medicine--and preparing TMA for the future.

PMID- 22876696
TI  - Health care 2020: where are we headed?

PMID- 22876697
TI  - A PCP's dystopian view of 2025.

PMID- 22876698
TI  - Future trending: the employed physician.

PMID- 22876699
TI  - The future of medicine?

PMID- 22876700
TI  - Predicting population health drivers in 2020: can we change direction?

PMID- 22876702
TI  - Coping with medical malpractice stress, Part I.

PMID- 22876701
TI  - The next 10 years of ehealth.

PMID- 22876703
TI  - Hiding in plain sight: H1N1 influenza presenting with respiratory failure and
      normal chest radiography.
AB  - Sepsis and respiratory failure are uncommon complications of infection with H1N1
      influenza. In the majority of cases of H1N1-associated sepsis and respiratory
      failure found in the literature, evidence of pneumonia or the acute respiratory
      distress syndrome was seen on chest radiography. This case report describes the
      clinical characteristics of a patient who presented with septic shock and multi
      system organ failure due to H1N1 influenza, but had normal chest radiography.
      Beyond describing a unique presentation of H1N1-related sepsis, this report
      highlights the need for clinicians to maintain a high index of suspicion for
      infection with H1N1 influenza in patients with sepsis and respiratory distress.

PMID- 22876704
TI  - Metaplastic breast cancer: a presentation of two cases and a review of the
      literature.
AB  - Metaplastic breast cancer has been difficult to diagnose and classify for a
      number of reasons. Its rarity prevents any important conclusions to be made, such
      as factors determining prognosis, immunohistochemistry patterns and successful
      treatment regimens. Here a number of studies of metaplastic breast cancer are
      discussed, along with the presentation of two cases.

PMID- 22876705
TI  - The non-compliant patient.

PMID- 22876706
TI  - Abdominal pain after the repair of an aortoiliac aneurysm.

PMID- 22876707
TI  - [A few months history of anemia and hypogastric colic pain].

PMID- 22876708
TI  - [Ismar Isidor Boas: myth and legend of gastroenterology].

PMID- 22876709
TI  - [Celiac disease and risk of colorectal neoplasia].
AB  - BACKGROUND: Although small bowel and esophagus neoplasia are recognized to occur
      more frequently in patients with celiac disease, the association with colorectal
      cancer is still controversial. OBJECTIVE: To determine the risk of colorectal
      neoplasia among patients with celiac disease. METHODS: A case-control study was
      conducted using the gastroenterology and endoscopy unit electronic data base.
      Patients with celiac disease and colonoscopy were regarded as cases and those
      without celiac disease and colonoscopy as controls. Patients were matched for
      age, sex, colonoscopy purpose and family history of colorectal cancer. The main
      outcome was the risk of colorectal polyps, adenomas, advanced lesions and cancer.
      The risk was expressed as odds ratio (OR) with the respective 95% confidence
      intervals (95% CI). RESULTS: Out of 178 celiac disease patients, 44 were included
      as cases. Eighty-eight non-celiac patients were included as controls. In cases,
      the presence of polyps, adenomas and advanced colonic lesions was 20%, 16% and
      4.5%, respectively. In controls, it was 15%, 9% and3.4%, respectively. The risk
      of polyps, adenomas and advanced colonic lesions was similar in both groups: OR
      1.48 (95% CI 0.59-3.73), OR 1.89 (95% CI 0.66-5.42) and OR 1.34 (95% CI 0.26
      7.05). No colorectal cancer was identified. CONCLUSION: The risk of colorectal
      neoplasia within this cohort of patients with celiac disease was similar to the
      control population.

PMID- 22876710
TI  - [Prevalence of serrated adenomas of the colon and association with synchronic and
      metachronic neoplastic lesions].
AB  - OBJECTIVE: To determine the prevalence of serrated adenomas (SA), the frequency
      of high grade dysplasia (HGD) and adenocarcinoma in these polyps, and the
      association with synchronic (SNL) and metachronic neoplastic lesions (MNL).
      METHODS: Reports from patients undergoing colonoscopy and polypectomy from
      January 2003 to April 2010, were obtained from our electronic database. SA were
      reanalyzed by two pathologists and classified on the basis of Snover's diagnostic
      criteria. The prevalence of these polyps and the clinical and endoscopic features
      were determined. SNL were defined by adenomas, cancer or advanced neoplastic
      lesions (ANL) (> 1 cm, HGD and/or >75% of villous component) in the same
      colonoscopy. MNL were identified in patients who underwent surveillance
      colonoscopies. An univariate and multivariate analysis was performed, looking for
      independent predictors of HGD/ cancer, SNL and MNL in patients with SA. RESULTS:
      The prevalence of SA was 0.87%. The mean age was 60 years old and 50.5% of
      patients were women. Most of the polyps were sessile (67%), small (63%) and
      located in ceco-ascending colon (47%). We found HGD in 4.4% ofSA and no
      adenocarcinoma. SNL was found in 31% ofpatients: 46% adenomas, 40.5% ANL and
      13.5% adenocarcinoma. MNL was found in 29% of patients: 25% SA, 31% adenomas, 44%
      ANL and 0% adenocarcinoma. Age over 60 years old was significantly associated
      with MNL [Odds ratio 3.7 (95% confidence interval 1.16-11.8)] and polyp's size
      higher than 1 cm with sessile SA histology [Odds ratio 8 (95% confidence interval
      1.28-49.4)]. CONCLUSION: The prevalence of SA was low. We found an association
      with neoplastic lesions. Therefore, it is important to establish specific
      guidelines for the management of these polyps.

PMID- 22876711
TI  - [Variation of intestinal fermentative profile after sequential therapy with
      rifaximin/probiotics].
AB  - INTRODUCTION: There is evidence suggesting that intestinal microbiota plays a
      role in the development of irritable bowel syndrome. Its activity can be
      indirectly assessed using the lactulose breath test. Antibiotics like rifaximin
      or probiotics can be used as therapeutic options for patients with irritable
      bowel syndrome. Our purpose was to evaluate the efficacy of a sequential
      treatment with rifaximin and probiotics in these patients. MATERIAL AND METHODS:
      We prospectively evaluated patients with diagnosis of irritable bowel syndrome
      according to Rome III criteria. Included patients had to fill in a questionnaire
      in order to assess their symptoms severity. A lactulose breath test was also
      performed in each case and a curve with the results of hydrogen concentration and
      time was elaborated. Then, the area under the curve was calculated After initial
      evaluation, patients received a seven-day treatment with rifaximin, followed by a
      ten-day course of probiotics. Thirty days after completion of treatment a new
      lactulose breath test along with a questionnaire were performed. RESULTS: We
      included 15 patients and 93% experienced a significant improvement of their
      symptoms as well as a significant reduction of the lactulose breath test values.
      CONCLUSION: Sequential treatment with rifaximin/probiotics seems to be effective
      for symptom and fermentative profile improvement in irritable bowel syndrome
      patients.

PMID- 22876712
TI  - Validation of the number connection test for identifying patients with minimal
      hepatic encephalopathy.
AB  - OBJECTIVES: Hepatic encephalopathy is a serious neuropsychiatric complication in
      advanced liver disease. The affected patients exhibit alterations in psychomotor
      and intellectual functions. The aims of this study were to identif the set
      ofnormal values for the number connection tests (NCT-A and NCT-B) in a population
      of volunteers without liver disease, to compare the values from this reference
      population with those from patients with cirrhosis without hepatic
      encephalopathy. MATERIALS AND METHODS: This study was performed in two referral
      hospitals in an urban setting from the city of La Plata. We evaluated the Number
      Connection Tests in 112 healthy subjects and 30 patients with cirrhosis without
      manifestations of hepatic encephalopathy. Time for performing the tests was
      measured in seconds. Results were compared according to age, gender, level of
      education and fine motor skills in both groups. RESULTS: Mean age in the control
      group was 45.3years; 56 (50%) were women. Mean age in the cirrhotic group was
      54.5 years; 8 (27%) were women. In the control group, the mean time for
      completing NCT-A and NCT-B was 60 s +/- 36s and 140 s +/- 60 s, respectively. In
      the cirrhotic group, the mean time for completing NCT-A and NCT-B was 114 s +/-
      64 y 232 s +/- 87 s, respectively (P = 0.00001 for both tests). 56.6% of
      cirrhotic patients took more than 2 SD to perform the NCT-A and 53.3%, more than
      2 SD to perform the NCT-B. CONCLUSION: We have obtained reference values for NCT
      A and NCT-B completing times in our healthy population. Cirrhotic patients
      without overt hepatic encephalopathy took double time than controls to complete
      NCT-A and NCT-B and over half of our patients would have minimal hepatic
      encephalopathy.

PMID- 22876713
TI  - [Liver diseases in rheumatoid and psoriatic arthritis].
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence, risk factors and
      features of liver diseases (LD) in rheumatoid and psoriatic arthritis. PATIENTS
      AND METHODS: From July 2007 to January 2010, 118 non-selected patients were
      consecutively examined. The assessment consisted of a medical record, biochemical
      studies and abdominal ultrasounds. The diagnosis of fatty liver disease was based
      on the ultrasound drug induced liver injury (DILI) was evaluated by the Maria
      Victorino system criteria. Liver biopsy associated with chronic administration of
      methotrexate was performed using the histological classification of Kleiner et
      al. For the statistical analysis chi square test with Yates correction, Student's
      t test or Mann-Whitney test were applied when appropriate. In the multivariate
      analysis a binary logistic regression was used. The threshold of significance was
      P < 0.05. RESULTS: LD was diagnosed in 47 patients (39.8%). The most frequent LD
      was fatty liver disease in 35 patients (29.7%), followed by DILI in 15 (12.7%),
      associated with non-steroidal anti-inflammatory drugs (NSAID). In the
      multivariate analysis, obesity was the only independent risk factor associated
      with fatty liver disease [Odds ratio (OR) 6.4 (confidence interval (CI) 95%: 2.5
      16.1; P = 0.000)] and fatty liver disease was the only risk factor associated
      with DILI [OR 7.7 (CI 95%: 2.0-30.0; P = 0.003)]. CONCLUSIONS: In our series,
      there was a high prevalence of LD, being fatty liver disease associated with
      obesity the most frequent finding. The second frequent disease was DILI, being
      fatty liver disease its main risk factor. The presence of obesity and the use of
      NSAIDs, especially in patients with steatosis, arise from our results as two
      conditions that require special care in handling this particular population.

PMID- 22876714
TI  - [Knowledge about viral hepatitis in a sample of Brazilian students from Vale do
      Araguaia, Legal Amazonia].
AB  - Viral and non-viral hepatitis are of great concern among developing nations
      because of their pathogenicity and virulence, and also their wide spreading by
      contaminated blood, food or water. The objective of this work was to evaluate the
      knowledge about hepatitis of academic students from three life/health sciences
      courses and also students from the last year of high school To measure the
      students' knowledge on hepatitis an instrument containing 22 questions was
      applied. Surprinsingly, it was verified that 41.9% of students had poor knowledge
      of viral hepatitis. Among the high school students, 31.8% ignored that viral
      hepatitis are infectious and transmissible diseases. Considering hepatitis
      symptomatology, just 18% of high school students declared knowledge of the
      symptons, but none of those cited the ictericia. Among the academic students,
      75.9% of nursing students had adequate knowledge of hepatitis, followed by
      pharmacy (51.3%), and biology students (18.2%). Nursing students had also higher
      scores of right answers regarding viral hepatitis and chronic disease. On
      contrary, biology and high school students had poor knowledge of that matter (37%
      and 44.5%, respectively). Less than 15% of nursing and pharmacy students did not
      know that viral hepatitis are sexually transmissible, whereas 78.6% of the 3rd
      year and 52.4% of the 4th year biology course ignored the sexual transmission of
      viral hepatitis. Still considering the same question, 54.5% of the high school
      students also ignored that viral hepatitis are sexually transmitted diseases.
      Important conclusions can be drawn from this study, since the higher hepatitis
      knowledge scores were found among nursing students, followed by pharmacy
      academics. However, biology students, which will serve as high school teachers,
      had poor and insufficient knowledge on hepatitis. This finding could explain the
      same poor disease knowledge among high school pupils.

PMID- 22876715
TI  - [Gastrinoma has an infrequent prevalence in pediatric age: a case report].
AB  - The authors present the clinical, laboratory and radiological findings suggestive
      ofgastrinoma in a patient 1 year and 9 months old. Laboratory tests obtained
      after fasting revealed elevated serum gastrin, supporting the suspected diagnosis
      of gastrinoma. In the endoscopy an elevated lesion with central depression was
      observed. The immunohistochemical examination revealed the benign nature of the
      tumor and the hyperplasia of argentaffin cells. Gastrinoma is a rare disease that
      predominantly affects young adults, but it must be considered in the pediatric
      group when clinical and laboratorial features of this disease are observed.

PMID- 22876716
TI  - Primary gastric rhabdomyosarcoma. Case report.
AB  - Rhabdomyosarcomas are rare and malignant tumors. There have been reported two
      histological types of gastric rhabdomyosarcomas, the pleomorphic and embryonal
      cell types. We report the case of a 53-year-old male with endoscopic diagnosis of
      a Bormann type III ulcer which revealed a gastric primary rhabdomyosarcoma.
      Ultrasound showed two liver lesions, two hepatic pedicle lymph nodes and a huge
      primary gastric tumor. CT scan revealed a primary gastric tumor. The patient is
      submitted to a distal gastrectomy with a Billroth II reconstruction and a
      resection of the distal liver metastases at segment IV The patient was discharged
      uneventfully on the eighth postoperative day. The gold standard for a final
      diagnoses is the immuno-histochemical staining of the endoscopic biopsy. There is
      very little information on the results of chemotherapy and the surgical treatment
      is the best choice.

PMID- 22876717
TI  - [Non biological artificial devices: what do they mean and what is their role
      today?].
AB  - Chronic liver diseases affect 10% of the world population. Five million people
      per year have acute liver failure in occidental countries. Since more than 30
      years now, orthotopic liver transplantation has been the treatment of choice for
      selected patients with these diseases, but the lack of enough organs to satisfy
      the increasing need oftransplantations as well as the elevated mortality of the
      operation in patients in critical condition, has led to search for additional
      therapies. Within the last years several therapies aiming to support liver
      function have developed in order to serve as a bridge to liver transplantation or
      as replace therapy allowing regeneration of the injured live. Biological and non
      biological devices providing liver support have been developed. The aim of this
      review is to analyze the technical aspects and the potential indications of the
      artificial non biological systems of liver support. In order to provide an
      adequate extracorporeal liver replacement, more complex and advanced techniques
      are needed, combining diffusion facilitated hemodialysis with adsorption and/or
      pheresis. Among these therapies, the more developed techniques are Single Pass
      Albumin Dialysis (SPAD), Molecular Adsorption Recirculating System (MARS) and the
      recently developed extracorporeal liver support combining albumin pheresis and
      fractioned adsorption (Prometheus).

PMID- 22876718
TI  - [Gastrointestinal Kaposi's sarcoma].

PMID- 22876719
TI  - [Low prevalence of inflammatory bowel disease in Peru].

PMID- 22876721
TI  - Immune responses to resistance exercise.
AB  - Resistance exercise induces changes in leukocyte redistribution, phenotypical
      surface expression and leukocyte functionality. Several factors have been shown
      to alter the temporal pattern and/or magnitude of response including manipulation
      of acute program variables, the aging process, and nutritional supplementation.
      Rest period length and load can modify the temporal pattern and/or magnitude of
      leukocytosis post exercise. Aging diminishes both the duration and magnitude of
      the post exercise leukocytosis and reduces leukocyte functionality. The few
      studies that assessed the effects of nutritional supplements (e.g., carbohydrate,
      whey protein, caffeine) peri-resistance exercise showed minimal effects on
      leukocyte responses. Sex differences exist in the timing and magnitude of
      leukocyte infiltration into skeletal muscle. The immune response to resistance
      exercise is only a small part of the recovery paradigm. A better understanding of
      how acute program variables and other factors such as aging, sex and nutritional
      supplementation affect the immune response to resistance exercise is important in
      the context of improving recovery, performance and health.

PMID- 22876722
TI  - Leucocytes, cytokines and satellite cells: what role do they play in muscle
      damage and regeneration following eccentric exercise?
AB  - Exercise-induced muscle damage is an important topic in exercise physiology.
      However several aspects of our understanding of how muscles respond to highly
      stressful exercise remain unclear In the first section of this review we address
      the evidence that exercise can cause muscle damage and inflammation in otherwise
      healthy human skeletal muscles. We approach this concept by comparing changes in
      muscle function (i.e., the force-generating capacity) with the degree of
      leucocyte accumulation in muscle following exercise. In the second section, we
      explore the cytokine response to 'muscle-damaging exercise', primarily eccentric
      exercise. We review the evidence for the notion that the degree of muscle damage
      is related to the magnitude of the cytokine response. In the third and final
      section, we look at the satellite cell response to a single bout of eccentric
      exercise, as well as the role of the cyclooxygenase enzymes (COX1 and 2). In
      summary, we propose that muscle damage as evaluated by changes in muscle function
      is related to leucocyte accumulation in the exercised muscles. 'Extreme' exercise
      protocols, encompassing unaccustomed maximal eccentric exercise across a large
      range of motion, generally inflict severe muscle damage, inflammation and
      prolonged recovery (> 1 week). By contrast, exercise resembling regular athletic
      training (resistance exercise and downhill running) typically causes mild muscle
      damage (myofibrillar disruptions) and full recovery normally occurs within a few
      days. Large variation in individual responses to a given exercise should, however
      be expected. The link between cytokine and satellite cell responses and exercise
      induced muscle damage is not so clear The systemic cytokine response may be
      linked more closely to the metabolic demands of exercise rather than muscle
      damage. With the exception of IL-6, the sources of systemic cytokines following
      exercise remain unclear The satellite cell response to severe muscle damage is
      related to regeneration, whereas the biological significance of satellite cell
      proliferation after mild damage or non-damaging exercise remains uncertain. The
      COX enzymes regulate satellite cell activity, as demonstrated in animal models;
      however the roles of the COX enzymes in human skeletal muscle need further
      investigation. We suggest using the term 'muscle damage' with care. Comparisons
      between studies and individuals must consider changes in and recovery of muscle
      force-generating capacity.

PMID- 22876723
TI  - Effects of moderate and high intensity exercise on T1/T2 balance.
AB  - Type 1 (TI) and Type 2 (T2) lymphocytes promote cell-mediated immunity and
      humoral immunity respectively. Evidence accumulated over the past two decades has
      demonstrated diverse responses of T1 and T2 cells to acute exercise or long-term
      training at moderate and high intensities. This brief review highlights the
      current findings from animal and human experimental models on the relationship
      between the T1 and T2 cell counts and the cytokines these cells produce, in
      response to moderate and high intensity exercise. The potential of using the
      T1/T2 balance as an indicator of immune function changes in response to exercise
      is discussed.

PMID- 22876724
TI  - IL-17, neutrophil activation and muscle damage following endurance exercise.
AB  - The T-cell subset Th17 is induced partly by interleukin (IL)-6 and activated by
      IL-23, and produces a proinflammatory cytokine IL-17. Since IL-6 increases
      dramatically following long-lasting endurance exercise, this response may also
      stimulate the induction of IL-17 and IL-23 after exercise. The aim of this study
      was to clarify the dynamics of IL-17 in association with endurance exercise
      induced muscle damage and inflammatory responses. Fourteen male triathletes
      participated in a duathlon race consisting of 5 km of running, 40 km of cycling
      and 5 km of running. Venous blood and urine samples were collected before,
      immediately after 1.5 h and 3 h after the race. Plasma and urine were analyzed
      using enzyme-linked immunosorbent assays (ELISA). Haematological and biochemical
      variables such as neutrophil activation marker (myeloperoxidase: MPO), muscle
      damage marker (myoglobin: Mb) and soluble receptor activator of nuclear factor
      (NF)-KB ligand (sRANKL) were also determined to estimate the biological and
      pathological significance. Plasma concentrations oflL-6 (+26.0x), MPO (+3.2x) and
      Mb (+4.9x) increased significantly immediately after the race and IL-17 and IL-23
      tended to increase. Furthermore, plasma concentrations of IL-12p40 and sRANKL
      increased significantly after the race. The measured parameters related to Thl 7
      cytokines in the urinary output were closely correlated with each other and
      muscle damage marker. These findings suggest that IL-17 induced by IL-6 and
      activated by IL-23 or other IL-17 producing-cells and IL-23 might promote
      neutrophil activation and muscle damage following prolonged endurance exercise.

PMID- 22876725
TI  - A soy-based supplement alters energy metabolism but not the exercise-induced
      stress response.
AB  - OBJECTIVE: To determine the changes in endurance capacity as well as in
      metabolic, hormonal and inflammatory markers induced by endurance training
      combined with a soy,protein based supplement. DESIGN: Randomized controlled study
      consisting of moderate endurance training without (GO) or with (G1) a soy protein
      based supplement. SUBJECTS: Two groups of 15 subjects (10 males and 5 females in
      each group): healthy sports students aged 23.6 +/- 1.9 years. MEASUREMENTS: Body
      composition (body mass (BM), body density (BD) by air displacement) and physical
      fitness (determined by treadmill ergometry) were measured at baseline and after 6
      weeks of the intervention; changes in circulating metabolic and hormonal
      parameters (glucose, lactate, urea, uric acid, ammonia, cortisol, insulin, IGF
      1), and exercise-induced stress and inflammatory markers (CK, LDH, myoglobin, hs
      CRP, IL-6, IL-10, blood cell counts) were determined after the intervention
      period in afield test (11.5 km running on hilly ground). RESULTS: 30 participants
      completed the 6-week study; 28 students were able to perform the field test. No
      significant changes in BM and BD were noted after intervention with only slight
      increases in running performance and maximum aerobic capacity in the total group
      (2%, p=0.016). Subjects in the G1 group showed significant improvements in
      running velocity and lower lactate values following the intervention (-12%,
      p=0,003). In addition, the G1 group showed significantly lower differences in the
      exercise-induced increase of metabolic parameters (triglycerides, uric acid) and
      insulin in the post-exercise recovery period. CONCLUSIONS: Our data suggest that
      moderate endurance training in combination with a soy-based protein supplement
      improves aerobic energy supply and metabolic function in healthy sports students,
      even without changes in body composition and without changes in the exercise
      induced stress and inflammatory reaction.

PMID- 22876726
TI  - Immune cell inflammatory cytokine responses differ between central and systemic
      compartments in response to acute exercise in mice.
AB  - BACKGROUND: Exhaustive exercise induces apoptosis and oxidative stress in
      systemic organs and tissues and is associated with increased levels of pro
      inflammatory cytokines. The effects of acute exercise on cytokine expression and
      apoptosis of immune cells in the central nervous system (CNS) have not been well
      characterized. PURPOSE: We investigated the effects of a single bout of strenuous
      exercise on the expression of TNF-alpha, IL-6, and IL-beta, as well as the
      apoptotic status of cells in the hippocampus of healthy mice. To compare central
      vs. systemic differences, cytokine expression in the intestinal lymphocytes of a
      subset of mice were also assessed. METHODS: Female C57BL/6 mice were divided into
      three groups: sedentary controls (NOTREAD) (n = 22), treadmill exercise with
      immediate sacrifice (TREAD-Imm) (n = 21), or treadmill exercise with sacrifice
      after 2 hours (TREAD-2h). TNF-alpha, IL-6, and IL-1beta expression in the
      hippocampus and intestinal lymphocytes were measured by Western blot analysis.
      Percentages of hippocampal cells undergoing apoptosis (Annexin+) or necrosis
      (Propidium Iodide+) were determined through flow cytometry. Plasma levels of 8
      isoprostane and corticosterone were measured using commercially available EIA
      kits. RESULTS: Acute treadmill exercise led to significant decreases in TNF-alpha
      (p<0.05) and increases in IL-6 (p<0.05) expression in the hippocampus of healthy
      mice. No effects of acute exercise on the apoptotic status of hippocampal cells
      were observed. In intestinal lymphocytes, the exercise bout led to significant
      increases in TNF-alpha (p<0.05), IL-6 (p<0.05), and IL-1beta (p<0.05). Acute
      exercise was associated with a significant increase in both plasma 8-isoprostane
      (p<0.05) and corticosterone (p<0.05) levels. CONCLUSION: Acute exercise
      differentially affects the pattern ofpro-inflammatory cytokine expression in the
      hippocampus compared to intestinal lymphocytes and, further, does not induce
      apoptosis in hippocampal cells.

PMID- 22876727
TI  - Exercise, physical activity and breast cancer: the role of tumor-associated
      macrophages.
AB  - Regular exercise and physical activity provide many health benefits and are
      encouraged by medical professionals for the primary prevention of and adjuvant
      treatment of breast cancer Current consensus in the discipline of exercise
      oncology is that both regular physical activity and exercise training exert some
      protective effect against breast cancer risk, and may reduce morbidity in some
      advanced cases. While there is growing interest in the role of exercise and
      physical activity in breast cancer prevention, it is currently unclear how
      exercise may modulate tumor behavior. The tumor microenvironment is populated by
      stromal cells such as fibroblasts and adipocytes, as well as macrophages. Termed
      tumor-associated macrophages (TAMs), these immune cells are highly plastic and
      respond to different signals from the cancer microenvironment, causing them to
      either display tumor-promoting or tumor-suppressing phenotypes. Because of such
      plasticity, there has been considerable interest by immunologists to develop
      immunotherapies based on skewing the behavior of TAMs to become cancer
      suppressive. Previous studies have indirectly shown the ability of exercise
      training to induce an anti-tumor effect of macrophages, although the studies did
      not address this in the tumor microenvironment. Nevertheless, this opens up the
      possibility that regular exercise training may exert a protective innate immune
      effect against breast cancer, potentially by inducing a cancer-suppressing
      phenotype of TAMs. This review will describe potential mechanisms through which
      exercise may modulate the behavior of TAMs.

PMID- 22876728
TI  - Impact of endotoxin exposure after exhausting exercise on the immune system in
      solid organ transplant recipients.
AB  - Subsequent to prolonged exhausting exercise a transient immunosuppression is
      often observed in athletes. This so-called "open window" results in a reduced
      resistance of the athletes to viral and bacterial infections after an exhaustive
      exercise bout. Concerning the effect of bacterial endotoxin contact after
      exhausting exercise in transplant recipients, who are innately immunosuppressed
      by their medication, no data exists at present. After performing 81 km cycling,
      including ascending more than 1800 m in altitude, peripheral blood from 10 male
      kidney transplant recipients and from 10 healthy controls matched for age and
      gender was obtained. Simulating contact of the athletes with a pathogen post
      exercise, the blood samples were incubated with Lipopolysaccharides (LPS).
      Thereafter microarray analysis was performed. Microarray analysis revealed a
      markedly oppositional pattern of gene expression in transplant recipients
      compared with their controls after LPS incubation. Especially immune response
      genes were significantly over-represented in controls immediately after the
      exhaustive exercise bout with LPS stimulation, whereas numerous apoptotic genes
      were over-represented in transplant recipients. Merging our previous data with
      these recent findings it should be discussed if transplant recipients need to
      reduce their immunosuppressive medication before performing exhaustive exercise.

PMID- 22876729
TI  - Ecological assessments of activities of daily living and personal experiences
      with Mobus, an assistive technology for cognition: a pilot study in
      schizophrenia.
AB  - Mobus is a cognitive orthotic designed for people with difficulties managing
      Activities of Daily Living (ADL), as encountered in schizophrenia. It provides a
      schedule manager as well as the possibility to report occurrences of symptomatic
      experiences. Receiving this information by Internet, caregivers can assist the
      patient rehabilitation process. Our aim was to explore the use and satisfaction
      of Mobus by people with schizophrenia. Nine outpatients tested Mobus for 6 weeks.
      Indicators of cognitive functioning and autonomy were measured with the CAmbridge
      Neuropsychological Tests Automated Battery (CANTAB) and the Independant Living
      Skills Scale (ILSS). On average, 42.6% of the planned ADL were validated and more
      than 1 symptom per week were reported. Mainly because of technical breakdown,
      more than 50% of the outpatients evaluated the Mobus satisfaction below 1.7/5,
      nevertheless 3 participants appreciated it greatly. Some enhancements were found
      on subscales of CANTAB and ILSS and some participants reported that they acquired
      planning skills by using Mobus. To ensure ease of use, refinements are needed
      from rehabilitation and technical approaches, especially to personalize the
      device. Discussions on ethical and methodological issues lead to an improved
      version of Mobus that will be tested with a larger sample size.

PMID- 22876730
TI  - Wheelchair components and pulmonary function in children with cerebral palsy.
AB  - OBJECTIVE: This study investigates the effects of four individual wheelchair
      components (upper extremity supports, lateral trunk supports, anterior pelvic
      belt, and 30 degree posterior seat tilt), on pulmonary function in prepubertal
      children with cerebral palsy (CP). METHODS: Participants who range in age from 5
      10 years were evaluated using four wheelchair components in six configurations
      (conditions 1-6) using a planar seating simulator. The Respironics Non Invasive
      Cardiac Output monitor (NICO) and MasterScreen Impulse Oscillometry System (IOS)
      measured pulmonary function parameters. Repeated measures ANOVA was used to
      analyze effect of wheelchair conditions on total airway resistance (R(AW)).
      RESULTS: Eight participants completed the protocol. R(AW) and minute ventilation
      (MV) varied with wheelchair condition. Lowest R(AW) was seen with two upper
      extremity supports or two lateral trunk supports. Differences were not
      significant (p = 0.253). CONCLUSIONS: The NICO and IOS, independent of
      participant effort, measured R(AW) and MV, which varied by wheelchair seating
      condition. More research is needed with a larger sample to determine seating
      components' impact on pulmonary function. These methods objectively measured
      pulmonary function of young children with CP in wheelchairs and could facilitate
      further research into benefits of wheelchair postural support components.

PMID- 22876731
TI  - Wheeled mobility device transportation safety in fixed route and demand
      responsive public transit vehicles within the United States.
AB  - An overview of the current status of wheelchair transportation safety in fixed
      route and demand-responsive, non-rail, public transportation vehicles within the
      US is presented. A description of each mode of transportation is provided,
      followed by a discussion of the primary issues affecting safety, accessibility,
      and usability. Technologies such as lifts, ramps, securement systems, and
      occupant restraint systems, along with regulations and voluntary industry
      standards have been implemented with the intent of improving safety and
      accessibility for individuals who travel while seated in their wheeled mobility
      device (e.g., wheelchair or scooter). However, across both fixed route and demand
      responsive transit systems a myriad of factors such as nonuse and misuse of
      safety systems, oversized wheeled mobility devices, vehicle space constraints,
      and inadequate vehicle operator training may place wheeled mobility device (WhMD)
      users at risk of injury even under non-impact driving conditions. Since WhMD
      related incidents also often occur during the boarding and alighting process, the
      frequency of these events, along with factors associated with these events are
      described for each transit mode. Recommendations for improving WhMD
      transportation are discussed given the current state of

PMID- 22876732
TI  - Effects of cross slopes and varying surface characteristics on the mobility of
      manual wheelchair users.
AB  - Surface characteristics of a cross slope can impact the ease with which a manual
      wheelchair (MWC) user propels across a surface. The purpose of this research was
      two-fold. Phase I of this research surveyed MWC users to identify cross slope
      scenarios that they reported to be more difficult to traverse compared to other
      common driving obstacles. Our survey results showed that, overall, cross slopes
      were harder to propel across than narrow and manual doors, and cross-slopes in
      inclement weather conditions were equal or more difficult than gravel and rough
      surfaces. Cross slopes with severe angles and those with compound angles (slope
      with cross-slope) were the most difficult to traverse. Phase II focused on
      identifying the responses (e.g., avoid, explore alternative, experience a sense
      of insecurity, no effect) people had when viewing pictures of various cross
      slopes scenarios (e.g., narrow space, compound angles, extreme weather) that
      wheelchair users encounter. These results showed that people reported that they
      would avoid or feel insecure on some cross-sloped surfaces, like the weather,
      that are not within our control, others, like compound angle and curb-cuts on
      slopes, that can be addressed in the construction of pathways or sidewalks.

PMID- 22876733
TI  - User evaluation of two electronic mobility aids for persons who are visually
      impaired: a quasi-experimental study using a standardized mobility course.
AB  - This study was conducted to enhance insight into the functionality, usability,
      and efficacy of two systematically selected Electronic Mobility Aids (EMA) aimed
      at obstacle detection and orientation. Eight persons who are visually impaired
      participated in a user evaluation of the UltraCane and the Miniguide. The
      participants' mobility performance was observed while completing a standardized
      indoor mobility course with their regular mobility aid, then with each EMA, and
      assessed in terms of speed, Percentage Preferred Walking Speed (PPWS), type and
      number of mobility incidents made. Interviews were administered to ascertain
      users' satisfaction with the functionality, effectiveness and specific features
      of the assistive devices. Walking speed and PPWS declined when using an EMA
      compared to the long cane. The mean total number of previously defined mobility
      incidents decreased significantly and also the type of mobility incidents
      changed. Generally, participants were quite satisfied with the use of the EMA,
      and detailed advantageous as well as disadvantageous aspects concerning
      functionality and certain features of both devices. The UltraCane and the
      Miniguide have proven to be effective on an indoor mobility course. Individual
      users' characteristics and preferences appear to be critical for their appraisal
      of the devices.

PMID- 22876734
TI  - A musical composition assistant for the people with severe physical and visual
      disabilities.
AB  - Current musical composition software on the commercial market is well-functioned
      for most users. However, there remains no program suitable for people with severe
      disabilities. In this paper a musical composition assistant is designed for
      individuals that require assistance using a musical composition tool, with
      special consideration for the people with physical and visual disabilities. In
      the single-switch mode a musical composition assistant first initiates a cursor,
      which moves across the top of each row (referred to as row scanning) for pitch,
      beat, octave, and halftone selection. To select a note option, the users have to
      press the mini switch connected to the left key when the cursor is over the row
      containing the desired entry. In the double-switch mode, the users can control
      two mini switches connected to the left and right key, with the right key to
      select and the left key to verify. The additional tools; scanning keyboard and
      scanning mouse were provided for some users with severe disabilities to write
      lyrics and share their composition ideas with others. After a 90-day experiment,
      10 participants carried out the composition learning task with 110 notes/hr
      composing speed.

PMID- 22876735
TI  - RESNA's position on wheelchairs used as seats in motor vehicles.
AB  - This position paper is based on the premise that those who ride seated in
      wheelchairs are entitled to equivalent occupant safety when they are traveling in
      motor vehicles. The document summarizes research and best practice for safety and
      selection of crashworthy wheelchairs with the requisite features required by the
      WC19 safety standard when it is necessary for individuals to use a wheelchair as
      a seat in a motor vehicle. Recommendations are based on data from accident and
      injury databases, prior research and a synopsis of the design, testing,
      performance and labeling requirements of ANSI and ISO voluntary industry
      standards for wheelchair transportation safety. This paper is intended for an
      audience of consumers, rehabilitation and health care professionals,
      manufacturers of wheelchairs and wheelchair transportation equipment and those
      who make reimbursement and public policy decisions.

PMID- 22876736
TI  - Porphyrin-lipid stabilized gold nanoparticles for surface enhanced Raman
      scattering based imaging.
AB  - A porphyrin-phospholipid conjugate with quenched fluorescence was utilized to
      serve as both the Raman dye and a stabilizing, biocompatible surface coating
      agent on gold nanoparticles. Through simple synthesis and validation with
      spectroscopy and confocal microscopy, we show that this porphyrin-lipid
      stabilized AuNP is a novel SERS probe capable of cellular imaging. To date, this
      is the first use of porphyrin as a Raman reporter molecule for SERS based
      imaging.

PMID- 22876737
TI  - Electrostatic-spray ionization mass spectrometry.
AB  - An electrostatic-spray ionization (ESTASI) method has been used for mass
      spectrometry (MS) analysis of samples deposited in or on an insulating substrate.
      The ionization is induced by a capacitive coupling between an electrode and the
      sample. In practice, a metallic electrode is placed close to but not in direct
      contact with the sample. Upon application of a high voltage pulse to the
      electrode, an electrostatic charging of the sample occurs leading to a bipolar
      spray pulse. When the voltage is positive, the bipolar spray pulse consists first
      of cations and then of anions. This method has been applied to a wide range of
      geometries to emit ions from samples in a silica capillary, in a disposable pipet
      tip, in a polymer microchannel, or from samples deposited as droplets on a
      polymer plate. Fractions from capillary electrophoresis were collected on a
      polymer plate for ESTASI MS analysis.

PMID- 22876738
TI  - In Iranian female and male adolescents, romantic love is related to hypomania and
      low depressive symptoms, but also to higher state anxiety.
AB  - BACKGROUND: Experiencing romantic love is important in individual development.
      Little is known about romantic love among adolescents in non-Western countries.
      The aim of the present study was to explore romantic love among Iranian male and
      female adolescents. METHOD: A total of 201 adolescents (mean age: 17.73 years)
      took part in the study; of these, 81 indicated they were experiencing romantic
      love at the time of survey, and 120 indicated they were not in love. Participants
      answered questionnaires related to affective states (hypomania, depressive
      symptoms, state and trait anxiety) and exercise, and completed a sleep log for
      seven consecutive nights. RESULTS: Compared to controls, participants in love
      displayed favourable hypomania scores, fewer depressive symptoms and increased
      concentration during the day. However, participants in love also had higher state
      anxiety scores. Moreover, hypomanic-like stages increased with duration of
      relationship in female, but not in male participants. CONCLUSIONS: The pattern of
      results suggests a favourable association between being currently in love and
      emotional and cognitive processes. Sleep, however, seemed unrelated to this
      specific state.

PMID- 22876739
TI  - Testing a service integration model: results from the HIV/AIDS initiative,
      ConnectHIV.
AB  - Staff of 20 AIDS Service Organizations (ASOs), grantees of the initiative
      ConnectHIV in the United States, developed a theoretical model of five categories
      of factors - external, community, organizational, staff, and client - that lead
      to effective service integration (SI) and took part in a self-assessment related
      to the model. The model was tested empirically using GEE analysis to assess the
      effect of ASO SI scores on client outcomes from participation in HIV/AIDS
      interventions involving case management with persons living with HIV/AIDS.
      Results showed that clients served by ASOs with more effective SI were more
      knowledgeable of HIV disease, healthier (higher CD4, lower viral load) and
      perceived themselves as healthier than clients in ASOs with less effective SI. In
      addition, clients at ASOs with more effective SI more often showed stronger gains
      in CD4 count over their time in the HIV/AIDS intervention than those at ASOs with
      less effective SI. Further research is needed on models and measurement of SI in
      order to effectively investigate the impact of HIV SI on client health outcomes.

PMID- 22876740
TI  - Evidence of the relative age effect in football in Australia.
AB  - The birth date distributions of elite male and female footballers in Australia,
      from junior youth (age 14 and upwards) to senior (professional) players, were
      examined. A statistically significant relative age effect was found among junior
      male players, reducing in effect with increasing age. An inter-year relative age
      effect that became apparent among the players at national level in the Under-17
      and Under-20 age groups, due to the timing of the respective World Cups for those
      age groups, was also identified. It is conjectured that this might lead to
      players born in certain years having a curtailed pathway in the elite game,
      leading to drop-out among this very elite group. In the case of women elite
      players, no significant relative age effect was found among youth players,
      possibly due to less fierce competition for places, although a significant effect
      was found to exist at senior elite level.

PMID- 22876741
TI  - Safety monitoring of herb-drug interactions: a component of pharmacovigilance.
AB  - Adverse drug reactions, including those resulting from interactions between
      herbal medicines and conventional drugs, are a public health problem worldwide.
      The need for pharmacovigilance for herb-drug interactions (HDIs) is essential for
      the identification and assessment of risks of using herbal products (questionable
      safety, efficacy and quality), which are not always tested with rigor, or often
      not subject to approval by regulatory agencies. Spontaneous and active
      surveillance conducted by national pharmacovigilance centres permits a rapid
      detection of potentially harmful combinations of products. The incidence and
      prevalence of HDIs are difficult to predict because of the underreporting of
      adverse effects. It is important for health professionals, consumers, regulatory
      authorities and suppliers of herbal medicines to be aware of the possible adverse
      effects and drug interactions caused when herbal medicines are co-administered
      with conventional drugs. National pharmacovigilance centres continue to play a
      significant role in increasing awareness of drug safety, in this case with HDIs.
      The authors' objective for this paper is to provide awareness among policy makers
      responsible for the design of appropriate pharmacovigilance practices and
      therefore to highlight the importance of pharmacovigilance in the safety
      monitoring of HDIs.

PMID- 22876742
TI  - Role of melatonin in mood disorders and the antidepressant effects of
      agomelatine.
AB  - INTRODUCTION: Disturbances of circadian rhythms and sleep play an important role
      in various types of mood disorders like major depressive disorder (MDD), bipolar
      depressive disorder (BPD) and seasonal affective disorder (SAD). Malfunctioning
      of the SCN-pineal-melatonin link has been suggested as the main cause for these
      disorders. As a rhythm-regulating factor and as a hormone involved in the
      regulation of sleep, melatonin is essential for the control of mood and behavior.
      AREAS COVERED: Melatonin's involvement in various mood disorders is reviewed
      based on studies undertaken in patients with MDD, BPD and SAD. The chemistry and
      metabolism of the newly introduced antidepressant, agomelatine, a MT1/MT2
      melatonin receptor agonist and 5-HT2c antagonist in brain areas involved in mood
      regulation are also discussed. Its clinical role in mood regulation,
      agomelatine's efficacy, safety and tolerability are also reviewed. EXPERT
      OPINION: Agomelatine, a melatonergic antidepressant with a rapid onset of action,
      has been shown effective in various types of mood disorders (e.g., MDD, BPD,
      SAD). Some studies find it superior to other common antidepressants (SSRIs,
      SNRIs) that are in clinical use today. Agomelatine's efficacy, good tolerability
      and safety profile suggest that it may become a preferred antidepressant in the
      near future.

PMID- 22876743
TI  - Coltsfoot as a potential cause of deep vein thrombosis and pulmonary embolism in
      a patient also consuming kava and blue vervain.
AB  - OBJECTIVE: To report a case of deep vein thrombosis (DVT) with symptomatic
      pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or
      blue vervain. CASE SUMMARY: A 27-year-old white male presented with leg pain and
      swelling, tachycardia, and pleuritic chest pain. He had no significant medical
      history. A medication history revealed extensive herbal medication use including:
      coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily
      flowers, wild dagga flowers, Diviners Three Burning Blend(r) (comprised of salvia
      divinorum, blue lily, and wild dagga), kava-kava, St. John's Wort, blue vervain,
      and Dreamer's Blend(r) (comprised of Calea zacatechichi, vervain, Entada rheedii,
      wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound
      and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable
      work-up was negative. The patient was treated with enoxaparin and warfarin and
      was discharged home. DISCUSSION: While no distinct agent can be identified as a
      sole cause of this venous thromboembolic event, coltsfoot could potentially
      affect coagulation through its effect on vascular endothelial cells as they
      regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and
      coagulation, particularly in the pulmonary vasculature. Kava and vervain have
      estrogenic properties. CONCLUSIONS: Of the medications consumed by this self
      proclaimed "herbalist," coltsfoot is a potential cause of venous thromboembolic
      disease (VTE).

PMID- 22876744
TI  - A time-dependent density functional study of a non-aromatic [1.1.1.1.1]
      pentaphyrin and its lutetium complex.
AB  - The molecular structures and absorption electronic spectra of two novel
      phototoxic pentapyrrolic expanded porphyrins (a isopentaphyrin derivative and its
      lutetium complex) have been studied at the density functional level and its time
      dependent extension (TDDFT). The geometries were optimized with three different
      exchange-correlation functionals (PBE0, B3LYP, and omegaB97XD) and the SV(P)
      basis set plus the pseudopotential method for the complex. With respect to the
      porphyrin, the structure of [1.1.1.1.1]-pentaphyrin and its lutetium complex are
      predicted much distorted due to the lack of conjugation. The lowest excitation
      energy band (experimental at 814 nm) for the free-base isopentaphyrin is well
      predicted by the omegaB97XD at 772 nm. The possible photodynamic reaction
      mechanisms (types I and II) were studied through the calculation of the electron
      affinity and ionization potentials in solvent, using the COSMO model.

PMID- 22876745
TI  - miRNA-146a expression positively regulates tumor necrosis factor-alpha-induced
      interleukin-8 production in mesenchymal stem cells and differentiated lung
      epithelial-like cells.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSC) can be differentiated into
      lung epithelial-like cells (MSC-EC) in vitro. The response of BM-MSC and MSC-EC
      to stimuli may vary because of their character and differentiation. We aimed to
      investigate the factors that may influence in vitro differentiation of BM-MSC to
      MSC-EC. We determined the response of BM-MSC, MSC-EC, bronchial epithelial cells,
      and alveolar epithelial cells to tumor necrosis factor (TNF)-alpha stimulation.
      We also investigated the changes in micro(mi)RNA-146a, miRNA-155, and TNF
      receptor 1 (TNFR1) expression after stimulation. Our results demonstrate that the
      addition of transforming growth factor-beta(1) and extracellular matrix collagen
      are required to facilitate such differentiation. After 3 weeks of culture, the
      morphological appearance and expression of airway epithelial markers, cytokeratin
      and Clara cell secretory protein, in MSC-EC were characteristics of lung
      epithelial cells. In response to TNF-alpha stimulation, the maximal interleukin
      (IL)-8 production by BM-MSC at the 24-h time point was 4.8 times greater compared
      with MSC-EC. TNF-alpha induced a significant increase in the expression of miRNA
      146a in BM-MSC as compared with MSC-EC. miRNA-155 expression remained unchanged
      after stimulation. TNFR1 mRNA also significantly increased in BM-MSC after TNF
      alpha stimulation. This was not observed in MSC-EC. Transfection with miRNA-146a
      mimics resulted in a significant increase of miRNA-146a expression and IL-8
      production in both types of cells. In contrast, miRNA-146a inhibitors reduced
      miRNA-146a expression and IL-8 production. Overexpression of miRNA-146a, which
      positively regulates TNF-alpha-induced IL-8 release, may enhance the inflammatory
      response in both BM-MSC and MSC-EC. The expression of miRNA-146a and the response
      to stimuli may be modulated through mature differentiation of BM-MSC.

PMID- 22876746
TI  - Serological diagnosis of autoimmune bullous skin diseases: prospective comparison
      of the BIOCHIP mosaic-based indirect immunofluorescence technique with the
      conventional multi-step single test strategy.
AB  - BACKGROUND: Various antigen-specific immunoassays are available for the
      serological diagnosis of autoimmune bullous diseases. However, a spectrum of
      different tissue-based and monovalent antigen-specific assays is required to
      establish the diagnosis. BIOCHIP mosaics consisting of different antigen
      substrates allow polyvalent immunofluorescence (IF) tests and provide antibody
      profiles in a single incubation. METHODS: Slides for indirect IF were prepared,
      containing BIOCHIPS with the following test substrates in each reaction field:
      monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A
      as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293
      cells. This BIOCHIP mosaic was probed using a large panel of sera from patients
      with pemphigus vulgaris (PV, n=65), pemphigus foliaceus (PF, n=50), bullous
      pemphigoid (BP, n=42), and non-inflammatory skin diseases (n=97) as well as from
      healthy blood donors (n=100). Furthermore, to evaluate the usability in routine
      diagnostics, 454 consecutive sera from patients with suspected immunobullous
      disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic
      and b) a panel of single antibody assays as commonly used by specialized centers.
      RESULTS: Using the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein
      3-, and NC16A-specific substrates were 90%, 98.5% and 100%, respectively. BP230
      was recognized by 54% of the BP sera. Specificities ranged from 98.2% to 100% for
      all substrates. In the prospective study, a high agreement was found between the
      results obtained by the BIOCHIP mosaic and the single test panel for the
      diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen's kappa
      between 0.88 and 0.97). CONCLUSIONS: The BIOCHIP mosaic contains sensitive and
      specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its
      diagnostic accuracy is comparable with the conventional multi-step approach. The
      highly standardized and practical BIOCHIP mosaic will facilitate the serological
      diagnosis of autoimmune blistering diseases.

PMID- 22876747
TI  - A non-invasive clinical application of wave intensity analysis based on ultrahigh
      temporal resolution phase-contrast cardiovascular magnetic resonance.
AB  - BACKGROUND: Wave intensity analysis, traditionally derived from pressure and
      velocity data, can be formulated using velocity and area. Flow-velocity and area
      can both be derived from high-resolution phase-contrast cardiovascular magnetic
      resonance (PC-CMR). In this study, very high temporal resolution PC-CMR data is
      processed using an integrated and semi-automatic technique to derive wave
      intensity. METHODS: Wave intensity was derived in terms of area and velocity
      changes. These data were directly derived from PC-CMR using a breath-hold spiral
      sequence accelerated with sensitivity encoding (SENSE). Image processing was
      integrated in a plug-in for the DICOM viewer OsiriX, including calculations of
      wave speed and wave intensity. Ascending and descending aortic data from 15
      healthy volunteers (30 +/- 6 years) data were used to test the method for
      feasibility, and intra- and inter-observer variability. Ascending aortic data
      were also compared with results from 15 patients with coronary heart disease (61
      +/- 13 years) to assess the clinical usefulness of the method. RESULTS: Rapid
      image acquisition (11 s breath-hold) and image processing was feasible in all
      volunteers. Wave speed was physiological (5.8 +/- 1.3 m/s ascending aorta, 5.0 +/
      0.7 m/s descending aorta) and the wave intensity pattern was consistent with
      traditionally formulated wave intensity. Wave speed, peak forward compression
      wave in early systole and peak forward expansion wave in late systole at both
      locations exhibited overall good intra- and inter-observer variability. Patients
      with coronary heart disease had higher wave speed (p <0.0001), and lower forward
      compression wave (p <0.0001) and forward expansion wave (p <0.0005) peaks. This
      difference is likely related to the older age of the patients' cohort, indicating
      stiffer aortas, as well as compromised ventricular function due to their
      underlying condition. CONCLUSION: A non-invasive, semi-automated and reproducible
      method for performing wave intensity analysis is presented. Its application is
      facilitated by the use of a very high temporal resolution spiral sequence. A
      formulation of wave intensity based on area change has also been proposed,
      involving no assumptions about the cross-sectional shape of the vessel.

PMID- 22876748
TI  - Doxycycline-mediated effects on persistent symptoms and systemic cytokine
      responses post-neuroborreliosis: a randomized, prospective, cross-over study.
AB  - BACKGROUND: Persistent symptoms after treatment of neuroborreliosis (NB) are well
      documented, although the causative mechanisms are mainly unknown. The effect of
      repeated antibiotic treatment has not been studied in detail. The aim of this
      study was to determine whether: (1) persistent symptoms improve with doxycycline
      treatment; (2) doxycycline has an influence on systemic cytokine responses, and;
      (3) improvement of symptoms could be due to doxycycline-mediated
      immunomodulation. METHODS/DESIGN: 15 NB patients with persistent symptoms >=6
      months post-treatment were double-blindly randomized to receive 200 mg of
      doxycycline or a placebo for three weeks. After a six-week wash-out period, a
      cross-over with a three-week course of a placebo or doxycycline was conducted.
      The primary outcome measures were improvement of persistent symptoms assessed by
      neurological examinations, a symptom severity score and estimation of the quality
      of life. The secondary outcome measure was changes in systemic cytokine
      responses. RESULTS: All 15 patients finished the study. No doxycycline-mediated
      improvement of post-treatment symptoms or quality of life was observed. Nor could
      any doxycycline-mediated changes in systemic cytokine responses be detected. The
      study was completed without any serious adverse events. DISCUSSION: No
      doxycycline-mediated improvement of post-treatment symptoms or quality of life
      was observed. Nor could any doxycycline-mediated changes in systemic cytokine
      responses be detected. The study was completed without any serious adverse
      events. To conclude, in this pilot study, doxycycline-treatment did not lead to
      any improvement of either the persistent symptoms or quality of life in post-NB
      patients. Accordingly, doxycycline does not seem to be the optimal treatment of
      diverse persistent symptoms post-NB. However, the results need to be confirmed in
      larger studies. TRIAL REGISTRATION: NCT01205464 (clinicaltrials.gov).

PMID- 22876749
TI  - Relationship between blood lipid profiles and pancreatic islet beta cell function
      in Chinese men and women with normal glucose tolerance: a cross-sectional study.
AB  - BACKGROUND: Dyslipidemia is present in people with diabetes as well as subjects
      with normal glucose tolerance (NGT). The purpose of this study was to investigate
      the relationship between lipid profiles and beta cell function in Chinese
      individuals with NGT but without history of diabetes or prediabetes. METHODS: A
      total of 893 men and 1454 women aged 18-76 years living in Sichuan, China, who
      were not being treated with lipid-lowering drugs were enrolled in this study.
      Insulin sensitivity (IR) was evaluated using the homeostasis model assessment -IR
      (HOMA-IR), beta-cell function was calculated by the following equation:
      DeltaI30/DeltaG30/ HOMA-IR (DeltaI30/DeltaG30: the ratio of incremental glucose
      and insulin 30 min after glucose intake). Multivariate linear regression analyses
      were performed to estimate the relationship between blood lipid and beta cell
      function as standardized coefficients (beta). RESULTS: beta cell function
      decreased in men and women with increasing age. We found inverse relationships
      between beta cell function and total cholesterol (TC) in men and women (beta = 
      0.157 and -0.113, respectively, both p < 0.001), low-density lipoprotein
      cholesterol (LDL-C; beta = -0.130 and -0.068, respectively, both p < 0.001),
      TC/high-density lipoprotein-cholesterol (HDL-C) ratio (beta = -0.084, p < 0.01
      and -0.096, p < 0.001), and triglycerides (TG) (women only; beta = -0.053, p <
      0.05). However, beta cell function was not associated with HDL-C in men or women
      (beta = -0.034 and 0.000, respectively, both p > 0.05) or the TG/HDL-C ratio
      (beta = -0.035 and -0.013, respectively, both p > 0.05). beta cell function was
      significantly worse in males than in females in all age groups, except in
      subjects aged > 70 years. CONCLUSIONS: Dyslipidemia is associated with
      dysfunction of pancreatic beta cells in subjects with NGT and this is
      particularly evident in people with elevated TC and LDL-C levels, especially
      males. TRIAL REGISTRATION NUMBER: #TR-CCH-Chi CTR-CCH-00000361.

PMID- 22876750
TI  - Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology.
AB  - A qualitative review of the epidemiological literature on the herbicide 2,4
      dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order
      to compare the exposure of the general population, bystanders and occupational
      groups, their urinary levels were also reviewed. In the general population, 2,4-D
      exposure is at or near the level of detection (LOD). Among individuals with
      indirect exposure, i.e. bystanders, the urinary 2,4-D levels were also very low
      except in individuals with opportunity for direct contact with the herbicide.
      Occupational exposure, where exposure was highest, was positively correlated with
      behaviors related to the mixing, loading and applying process and use of personal
      protection. Information from biomonitoring studies increases our understanding of
      the validity of the exposure estimates used in epidemiology studies. The 2,4-D
      epidemiology literature after 2001 is broad and includes studies of cancer,
      reproductive toxicity, genotoxicity, and neurotoxicity. In general, a few
      publications have reported statistically significant associations. However, most
      lack precision and the results are not replicated in other independent studies.
      In the context of biomonitoring, the epidemiology data give no convincing or
      consistent evidence for any chronic adverse effect of 2,4-D in humans.

PMID- 22876752
TI  - A computerized physician order entry set designed to improve safety of
      intravenous haloperidol utilization: a retrospective study in agitated
      hospitalized patients.
AB  - BACKGROUND: Intravenous haloperidol can increase the risk for corrected QT (QTc)
      interval prolongation, torsades de pointes (TdP) and sudden death. OBJECTIVE: The
      purpose of this study was to examine the effects of implementation of a
      computerized physician order entry (CPOE) set on adherence to monitoring
      parameters, maximum and cumulative doses, and identification or mitigation of
      risk factors for QTc prolongation in patients prescribed intravenous haloperidol.
      METHODS: A retrospective cohort study of medically ill hospitalized inpatients
      prescribed intravenous haloperidol was conducted. Data were collected for two
      distinct 1-year time periods: the pre-CPOE set period (30 June 2007 through 30
      June 2008) and the post-CPOE set period (1 January 2009 through 1 January 2010).
      The CPOE set was implemented on 1 October 2008. RESULTS: A total of 151 subjects
      were included; 84 subjects were in the pre-CPOE set group and 67 subjects were in
      the post-CPOE set group. Following CPOE set implementation, subjects in the post
      CPOE group, compared with the pre-CPOE group, were more likely to receive a 24
      hour cumulative dose of intravenous haloperidol <2 mg (Fisher's exact test; p <
      0.048), have a baseline ECG (Fisher's exact test; p = 0.045), have a follow-up
      ECG within 24 hours of intravenous haloperidol administration (Fisher's exact
      test; p = 0.009) and have a magnesium value assessed at the time of intravenous
      haloperidol administration (Fisher's exact test; p = 0.004). CONCLUSION: This
      study reports on the successful implementation of a CPOE set designed to improve
      the safety of intravenous haloperidol administration in medically ill patients.

PMID- 22876751
TI  - Mitigating an undesirable immune response of inherent susceptibility to cutaneous
      leishmaniosis in a mouse model: the role of the pathoantigenic HISA70 DNA
      vaccine.
AB  - Leishmania major is the major cause of cutaneous leishmaniosis (CL) outside of
      the Americas. In the present study we have cloned six Leishmania genes (H2A, H2B,
      H3, H4, A2 and HSP70) into the eukaryotic expression vector pCMVbeta-m2a,
      resulting in pCMV-HISA70m2A, which encodes all six pathoantigenic proteins as a
      single polyprotein. This expression plasmid has been evaluated as a novel vaccine
      candidate in the BALB/c mouse model of CL. The DNA vaccine shifted the immune
      response normally induced by L. major infection away from a Th2-specific pathway
      to one of basal susceptibility. Immunization with pCMV-HISA70m2A dramatically
      reduced footpad lesions and lymph node parasite burdens relative to infected
      control mice. Complete absence of visceral parasite burden was observed in all 12
      immunized animals but not in any of the 24 control mice. Moreover, vaccinated
      mice produced large amounts of IFN-gamma, IL-17 and NO at 7 weeks post-infection
      (pi), and they showed lower arginase activity at the site of infection, lower IL
      4 production and a weaker humoral immune response than infected control mice.
      Taken together, these results demonstrate the ability of the HISA70 vaccine to
      shift the murine immune response to L. major infection away from an undesirable,
      Th2-specific pathway to a less susceptible-like pathway involving Th1 and Th17
      cytokine profiles.

PMID- 22876753
TI  - Improvement of hip abductor muscle weakness after lumbar decompressive surgery.
AB  - INTRODUCTION: Degenerative lumbar spinal disorder is common in Japan, and the L5
      nerve root is commonly involved in this disorder. The symptoms of L5
      radiculopathy are irradiating lateral leg pain, and numbness and weakness of
      tibialis anterior and the hip abductor muscle. There has been only one report on
      the results of surgery for hip abductor muscle weakness caused by degenerative
      lumbar spinal disorder. PATIENTS AND METHODS: In this study, we analyzed the
      strength of the hip abductor muscle before and after decompressive surgery in 26
      cases and the relationship between the lumbar disc herniation (LDH) and lumbar
      spinal canal stenosis (LSCS) groups. RESULTS: Of the total 26 cases, muscle
      strength improved in 23 cases (88%), with complete recovery in 17 cases (65%). In
      the LDH group, the improvement rate was 92%. In the LSCS group, the improvement
      rate was 68%. Although the improvement rate for the LDH group was higher than
      that for the LSCS group, the difference was not significant (P = 0.054).
      DISCUSSION: Decompressive surgery may be an effective method to improve hip
      abductor muscle weakness in degenerative lumbar spinal disorder.

PMID- 22876754
TI  - Therapeutic potential of TDT 067 (terbinafine in Transfersome): a carrier-based
      dosage form of terbinafine for onychomycosis.
AB  - INTRODUCTION: Current topical treatments for onychomycosis are unsatisfactory.
      New topical agents that offer efficacy without the potential adverse effects of
      oral antifungal therapy would benefit patients with this condition and encourage
      a greater treatment rate. AREAS COVERED: Currently available topical therapies
      are reviewed, and new approaches for enhancing delivery of the established
      antifungal terbinafine through the nail are summarized. We focus on the use of
      ultra-deformable lipid vesicles to facilitate delivery of terbinafine to the nail
      and surrounding tissue. TDT 067 (terbinafine in Transfersome) is the only such
      therapy in development for onychomycosis, and we review published preclinical and
      clinical studies on this formulation. EXPERT OPINION: TDT 067 offers the use of
      new technology to deliver an established antifungal, terbinafine. Preclinical
      data suggest that the Transfersome accelerates entry of terbinafine released from
      TDT 067 into fungi and potentiates its antifungal effects, resulting in enhanced
      activity, compared with conventional terbinafine. This translated into high rates
      of mycological cure and evidence of clinical effect in a study of TDT 067
      administered twice daily for 12 weeks in patients with onychomycosis. An ongoing
      Phase-III trial involving more than 700 patients treated for 48 weeks is
      investigating the efficacy and safety of TDT 067.

PMID- 22876755
TI  - The effect of rowing to exhaustion on frontal plane angular changes in the lumbar
      spine of elite rowers.
AB  - Lumbar spine injury is common in rowers and examination of spinal kinematics may
      improve the understanding of this injury's prevalence. This study aimed to
      examine the range of frontal plane angular displacement (AD) in the lumbar spine
      at L3 during ergometer rowing and to investigate the effect of exhaustion on
      lumbar kinematics. Twelve elite male rowers completed an incremental test on a
      concept 2 ergometer. Lumbar AD at L3 was measured continually throughout the
      rowing trial using a Spectrotilt Inclinometer and blood lactate was sampled at 3
      minute intervals. AD of between 4.7 degrees  and 8.8 degrees  was recorded at L3.
      There was a significant increase in AD between the first and last stage of the
      test (mean increase = 4.1 +/- 1.94 degrees , 95% Confidence Interval [CI], 2.9 to
      5.3 degrees , t = 7.36, P = 0.000014). Incremental rise in AD was associated with
      an incremental rise in blood lactate but regression confirmed that only stroke
      rate was a significant predictor for increasing angle. Thus there is a
      statistically significant increase in frontal plane AD at L3 over the course of
      an incremental exercise test although it cannot be confirmed if this is as a
      result of exhaustion. The values of AD confirm that there is motion in the
      frontal plane in ergometer rowing.

PMID- 22876756
TI  - Current challenges in female veterans' health.
AB  - Abstract   Women in the U.S. military are technically barred from serving in
      combat specialties, positions, or units; however, since Operation Desert Storm,
      women have served in forward positions in greater numbers. This increased
      involvement in combat zones has resulted in exposures to trauma, injury, and a
      myriad of environmental hazards associated with modern war. Some of these hazards
      present new health risks specifically relevant to women who have been deployed to
      or recently returned from Iraq or Afghanistan or both. To address this evolving
      public health concern, the Society for Women's Health Research (SWHR) convened a
      1-day interdisciplinary scientific conference, with speakers and attendees from
      civilian, military, and veteran settings. The purpose of the conference was to
      reveal the state-of-the-science on the health of the female veteran and to focus
      attention on recent advances in biomedical research related to female veterans'
      health. The following topics were discussed: mental health (posttraumatic stress
      disorder [PTSD] and depression), urogenital health, musculoskeletal health, and
      traumatic brain injury (TBI).

PMID- 22876757
TI  - Ultrasound elastography is not superior to grayscale ultrasound in predicting
      malignancy in thyroid nodules.
AB  - BACKGROUND: Several studies have evaluated the ability of ultrasound elastography
      (USE) to diagnose malignant nodules. However, these studies had important
      limiting factors, selection bias and small sample size. The aims of the present
      study were to prospectively assess, in a large group of patients, the diagnostic
      power of USE for detecting malignancy in thyroid nodules, and to compare this
      technique with B-mode grayscale ultrasonography (BUS) and power Doppler
      ultrasonography (PD). METHOD: There were 194 patients with 237 thyroid nodules
      who were examined using BUS, PD, and USE. USE scores were classified according to
      the elasticity: score 1 as high, score 2 as intermediate, and score 3 as low
      (i.e., a high degree of stiffness). Fine-needle aspiration cytology (FNAC) was
      performed in all nodules at least two different times. Nodules having two benign
      FNAC readings that did not change the diameter during a 6-month follow-up period
      were classified as benign. Patients having thyroid nodules with indeterminate,
      suspicious, or malignant cytology had total or hemithyroidectomy to remove the
      nodule and treat the malignancy. RESULTS: Fifty eight (25%) nodules in 45 (23%)
      patients were found to be malignant. USE had a limited sensitivity and a positive
      predictive value in detecting malignant thyroid nodules and was not superior to
      BUS. USE had almost the same specificity and a negative predictive value as BUS.
      A power Doppler type-3 pattern was not of sufficient sensitivity to detect
      malignancies in thyroid nodules. CONCLUSIONS: In contrast to earlier reports,
      this current study noted a lower sensitivity and specificity of USE for the
      diagnosis of malignancy in thyroid nodules than previously reported.

PMID- 22876758
TI  - The packaging of different cargo into enveloped viral nanoparticles.
AB  - Viral nanoparticles used for biomedical applications must be able to discriminate
      between tumor or virus-infected host cells and healthy host cells. In addition,
      viral nanoparticles must have the flexibility to incorporate a wide range of
      cargo, from inorganic metals to mRNAs to small molecules. Alphaviruses are a
      family of enveloped viruses for which some species are intrinsically capable of
      systemic tumor targeting. Alphavirus virus-like particles, or viral
      nanoparticles, can be generated from in vitro self-assembled core-like particles
      using nonviral nucleic acid. In this work, we expand on the types of cargo that
      can be incorporated into alphavirus core-like particles and the molecular
      requirements for packaging this cargo. We demonstrate that different core-like
      particle templates can be further enveloped to form viral nanoparticles that are
      capable of cell entry. We propose that alphaviruses can be selectively modified
      to create viral nanoparticles for biomedical applications and basic research.

PMID- 22876759
TI  - Application of Heisenberg's S matrix program to the angular scattering of the H +
      D2(v(i) = 0, j(i) = 0) -> HD(v(f) = 3, j(f) = 0) + D reaction: piecewise S matrix
      elements using linear, quadratic, step-function, and top-hat parametrizations.
AB  - A previous paper by Shan and Connor (Phys. Chem. Chem. Phys. 2011, 13, 8392)
      reported the surprising result that four simple parametrized S matrices can
      reproduce the forward-angle glory scattering of the H + D(2)(v(i)=0,j(i)=0) ->
      HD(v(f)=3,j(f)=0) + D reaction, whose differential cross section (DCS) had been
      computed in a state-of-the-art scattering calculation for a state-of-the-art
      potential energy surface. Here, v and j are vibrational and rotational quantum
      numbers, respectively, and the translational energy is 1.81 eV. This paper asks
      the question: Can we replace the analytic functions (of class C(omega)) used by
      Shan-Connor with simpler mathematical functions and still reproduce the forward
      angle glory scattering? We first construct S matrix elements (of class C(0))
      using a quadratic phase and a piecewise-continuous pre-exponential factor
      consisting of three pieces. Two of the pieces are constants, with one taking the
      value N (a real normalization constant) at small values of the total angular
      momentum number, J; the other piece has the value 0 at large J. These two pieces
      are joined at intermediate values of J by either a straight line, giving rise to
      the linear parametrization (denoted param L), or a quadratic curve, which defines
      the quadratic parametrization (param Q). We find that both param L and param Q
      can reproduce the glory scattering for center-of-mass reactive scattering angles,
      theta(R) ? 30 degrees . Second, we use a piecewise-discontinuous pre-exponential
      factor and a quadratic phase, giving rise to a step-function parametrization
      (param SF) and a top-hat parametrization (param TH). We find that both param SF
      and param TH can reproduce the forward-angle scattering, even though these class
      C(-1) parametrizations are usually considered too simplistic to be useful for
      calculations of DCSs. We find that an ultrasimplistic param THz, which is param
      TH with a phase of zero, can also reproduce the glory scattering at forward
      angles. The S matrix elements for param THz are real and consist of five nonzero
      equal values, given by S(J) = 0.02266, for the window, J = 21(1)25. Param THz is
      sufficiently simple that we can derive closed forms for the partial wave
      scattering amplitude, f(theta(R)), and the near-side (N) and far-side (F)
      subamplitudes. We show that window representations of f(theta(R)) provide
      important insights into the range of J values that contribute to the reaction
      dynamics. Other theoretical techniques used are NF theory for the analysis of
      DCSs and full and NF local angular momentum theory, in both cases including up to
      three resummations of f(theta(R)) before making the NF decomposition. Finally, we
      investigate the accuracy of various semiclassical glory theories for the DCS of
      param L. By varying one phase parameter for param L, we show that the uniform
      semiclassical approximation is accurate from theta(R) = 0 degrees  to close to
      theta(R) = 180 degrees . Our approach is an example of a "weak" form of
      Heisenberg's S matrix program, which does not use a potential energy surface(s);
      rather it focuses on the properties of the S matrix. Our method is easy to apply
      to DCSs from experimental measurements or from computer simulations.

PMID- 22876760
TI  - Characterization of a protein conjugate using an asymmetrical-flow field-flow
      fractionation and a size-exclusion chromatography with multi-detection system.
AB  - In this study we present detailed characterization of a protein-PEG conjugate
      using two separation techniques, that is, asymmetrical-flow field-flow
      fractionation (AF4) and size-exclusion chromatography (SEC), which were online
      coupled to a series of successively connected detectors: an ultraviolet, a
      multiangle light-scattering, a quasi-elastic light-scattering, and a refractive
      index detector (UV-MALS(QELS)-RI). Matrix-assisted laser-desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) was used as a complementary
      characterization technique. The results of AF4 as well as SEC on two columns
      connected in series, with both separation techniques coupled to a multidetection
      system, indicate the uniform molar mass and chemical composition of the
      conjugate, that is, the molar ratio of protein to PEG is 1/1, the presence of
      minute amounts of residual unreacted protein and the aggregates with the same
      chemical composition as that of the conjugate. Since the portion of aggregated
      species is smaller in the acetate buffer solution containing 5% sorbitol than in
      the acetate buffer solution with 200-mM sodium chloride, the former buffer
      solution is more suitable for conjugate storage. The separation using only one
      SEC column results in poorly resolved peaks of the PEGylated protein conjugate
      and the aggregates, whereas MALDI-TOF MS analysis reveal the presence of the
      residual protein, but not the aggregates.

PMID- 22876761
TI  - Preparation of Au/CeO2 exhibiting strong surface plasmon resonance effective for
      selective or chemoselective oxidation of alcohols to aldehydes or ketones in
      aqueous suspensions under irradiation by green light.
AB  - Au/CeO(2) samples with various Au contents were prepared by the multistep (MS)
      photodeposition method. Their properties including Au particle size, particle
      dispersion, and photoabsorption were investigated and compared with properties of
      samples prepared by using the single-step (SS) photodeposition method. The MS-
      and SS-Au/CeO(2) samples were used for selective oxidation of benzyl alcohols to
      corresponding benzaldehydes in aqueous suspensions under irradiation by visible
      light from a green LED, and the correlations between reaction rates and physical
      properties of the MS- and SS-Au/CeO(2) samples were investigated. Difference in
      the two photodeposition methods was reflected in the average size and number of
      Au nanoparticles, for example, 92 nm and 1.3 * 10(12) (g-Au/CeO(2))(-1) for MS
      photodeposition and 59 nm and 4.8 * 10(12) (g-Au/CeO(2))(-1) for SS
      photodeposition in the case of 1.0 wt % Au samples. Fixation of larger Au
      particles resulted in strong photoabsorption of the MS-Au/CeO(2) samples at
      around 550 nm due to the surface plasmon resonance, and the Kubelka-Munk function
      of the photoabsorption linearly increased with increase in Au content up to 2.0
      wt %, in contrast to the photoabsorption of SS-Au/CeO(2) samples, which was weak
      and was saturated even at around 0.5 wt %. Due to the strong photoabsorption, the
      MS-Au/CeO(2) samples exhibited reaction rates approximately twice larger than
      those of SS-Au/CeO(2) samples with the same Au contents, and apparent quantum
      efficiency of MS-Au/CeO(2) reached 4.9% at 0.4 mW cm(-2). Linear correlations
      were observed between reaction rates (r) and surface area of Au nanoparticles (S)
      in both MS- and SS-Au/CeO(2) samples, though the two slopes of r versus S plots
      were different, suggesting that oxidation of benzyl alcohol occurred on the Au
      surface and that S was one of the important factors controlling the reaction
      rate. Photocatalytic oxidation of benzyl alcohol having an amino group revealed
      that the Au/CeO(2) photocatalyst exhibited high chemoselectivity toward the
      hydroxyl group of alcohol, i.e, the Au/CeO(2) photocatalyst almost quantitatively
      converted aminobenzyl alcohol to aminobenzaldehyde with 99% yield.

PMID- 22876762
TI  - Lapatinib  and renal cell carcinoma.
AB  - INTRODUCTION: Major progress in treatment of renal cell carcinoma (RCC) has
      occurred in the past decade. AREAS COVERED: This review reports the background on
      the potential implication of the EGF/EGFR pathway in RCC, the different data on
      EGFR positivity in RCC and results from prospective Phase II and III trials on
      lapatinib in RCC, along with other EGF/EGFR inhibitors. EXPERT OPINION: Despite
      important progress and the real revolution of the past decade in treatment of
      RCC, treatment still remains palliative most of the time. To improve treatment,
      it is necessary to understand whether a specific population could be selected on
      a molecular feature of the tumor. Until there is better knowledge of the biology,
      further development of drugs such as lapatinib cannot be supported.

PMID- 22876763
TI  - pH and redox dual responsive nanoparticle for nuclear targeted drug delivery.
AB  - To mimic the clinic dosing pattern, initially administering high loading dose and
      then low maintenance dose, we designed a novel poly(2-(pyridin-2
      yldisulfanyl)ethyl acrylate) (PDS) based nanoparticle delivery system. Side chain
      functional PDS was synthesized by free radical polymerization. Polyethylene
      glycol and cyclo(Arg-Gly-Asp-d-Phe-Cys) (cRGD) peptide was conjugated to PDS
      through thiol-disulfide exchange reaction to achieve RPDSG polymer. RPDSG/DOX,
      RPDSG nanoparticle loaded with doxorubicin, was fabricated by cosolvent dialysis
      method. The size of the nanoparticles was 50.13 +/- 0.5 nm in PBS. The RPDSG/DOX
      nanoparticle is stable in physiological condition while quickly releasing
      doxorubicin with the trigger of acidic pH and redox potential. Furthermore, it
      shows a two-phase release kinetics, providing both loading dose and maintenance
      dose for cancer therapy. The conjugation of RGD peptide enhanced the cellular
      uptake and nuclear localization of the RPDSG/DOX nanoparticles. RPDSG/DOX
      exhibits IC(50) close to that of free doxorubicin for HCT-116 colon cancer cells.
      Due to the synergetic effect of RGD targeting effect and its two-phase release
      kinetics, RPDSG/DOX nanoparticles display significantly higher anticancer
      efficacy than that of free DOX at concentrations higher than 5 MUM. These results
      suggest that RPDSG/DOX could be a promising nanotherapeutic for tumor-targeted
      chemotherapy.

PMID- 22876764
TI  - Highly flexible method for the fabrication of photonic crystal slabs based on the
      selective formation of porous silicon.
AB  - A novel fabrication method of Si photonic slabs based on the selective formation
      of porous silicon is reported. Free-standing square lattices of cylindrical air
      holes embedded in a Si matrix can be achieved by proton beam irradiation followed
      by electrochemical etching of Si wafers. The photonic band structures of these
      slabs show several gaps for the two symmetry directions for reflection through
      the z-plane. The flexibility of the fabrication method for tuning the frequency
      range of the gaps over the near- and mid-infrared ranges is demonstrated. This
      tunability can be achieved by simply adjusting the main parameters in the
      fabrication process such as the proton beam line spacing, proton fluence, or
      anodization current density. Thus, the reported method opens a promising route
      towards the fabrication of Si-based photonic slabs, with high flexibility and
      compatible with the current microelectronics industry.

PMID- 22876765
TI  - Ice-phobic surfaces that are wet.
AB  - Ice formation on surfaces and structures produces damage and inefficiencies that
      negatively impact all manners of activities. Not surprisingly, for a long time,
      an unmet challenge has been to design materials capable of minimizing or even
      eliminating the formation of ice on the surface of the material. In recent years,
      there were significant efforts to develop such ice-phobic surfaces by building on
      the advances made with superhydrophobic materials since these, by definition,
      tend to repel water. However, a robust response includes the ability to deter the
      formation of ice when a substrate colder than the freezing temperature is exposed
      either to impacting water droplets or water vapor (i.e., frost formation). In the
      latter case, superhydrophobic surfaces in high humidity conditions were shown to
      allow significant ice accumulation. Consequently, a new design idea was needed.
      In this issue of ACS Nano, it is shown how a liquid-infiltrated porous solid,
      where the liquid strongly wets and is retained within the material, has many of
      the properties desired for an ice-phobic substrate. The composite material
      exhibits low contact angle hysteresis so only small forces are needed to provoke
      droplets to slide off of a cold substrate. This new slippery surface shows many
      characteristics required for ice-phobicity, and a method is demonstrated for
      applying this kind of material as a coating on aluminum. Ice may have met its
      match.

PMID- 22876766
TI  - Language and ageing - exploring propositional density in written language -
      stability over time.
AB  - This study investigated the stability of propositional density (PD) in written
      texts, as this aspect of language shows promise as an indicator and as a
      predictor of language decline with ageing. This descriptive longitudinal study
      analysed written texts obtained from the Australian Longitudinal Study of Women's
      Health in which participants were invited to respond to an open-ended question
      about their health. The 635 texts used for this study were taken from 127 middle
      aged women who responded to this question on each of the five surveys conducted
      at 3-year intervals over a 16-year period. The study made use of an automated PD
      rater (CPIDR-3) for the analysis. PD was found to be a stable measure over time
      when comparing the grouped data, but there was between- and within-subject
      variation over time. Further research is needed to explore the valid use of this
      measure in research into language and ageing.

PMID- 22876767
TI  - Segmental and positional effects on children's coda production: comparing
      evidence from perceptual judgments and acoustic analysis.
AB  - Children's early productions are highly variable. Findings from children's early
      productions of grammatical morphemes indicate that some of the variability is
      systematically related to segmental and phonological factors. Here, we extend
      these findings by assessing 2-year-olds' production of non-morphemic codas using
      both listener decisions and acoustic analyses. Results showed that utterance
      position and coda manner influence perception, in that more stop codas were
      perceived utterance-finally compared to utterance-medially but fricative codas
      were perceived equally across utterance positions. Acoustic analyses showed some
      convergence to listeners' perception in that there were more cues associated with
      stops utterance-finally compared to utterance-medially. However, there was some
      divergence between the two methods in that acoustic cues to coda segments were
      also present in the majority of cases where a coda was not perceived. These
      findings provide insight into both the nature of children's emerging phonological
      representations and the effectiveness of coda transcription across segment types.

PMID- 22876768
TI  - Proposal for classifying the severity of speech disorder using a fuzzy model in
      accordance with the implicational model of feature complexity.
AB  - The objective of this study is to create a new proposal for classifying the
      severity of speech disorders using a fuzzy model in accordance with a linguistic
      model that represents the speech acquisition of Brazilian Portuguese. The fuzzy
      linguistic model was run in the MATLAB software fuzzy toolbox from a set of fuzzy
      rules, and it encompassed three input variables: path routing, level of
      complexity and phoneme acquisition. The output was the Speech Disorder Severity
      Index, and it used the following fuzzy subsets: severe, moderate severe, mild
      moderate and mild. The proposal was used for 204 children with speech disorders
      who were monolingual speakers of Brazilian Portuguese. The fuzzy linguistic model
      provided the Speech Disorder Severity Index for all of the evaluated phonological
      systems in a fast and practical manner. It was then possible to classify the
      systems according to the severity of the speech disorder as severe, moderate
      severe, mild moderate and mild; the speech disorders could also be differentiated
      according to the severity index.

PMID- 22876769
TI  - Is weak oral language associated with poor spelling in school-age children with
      specific language impairment, dyslexia or both?
AB  - The purpose of this study was to test the hypothesis that word reading accuracy,
      not oral language, is associated with spelling performance in school-age
      children. We compared fourth grade spelling accuracy in children with specific
      language impairment (SLI), dyslexia or both (SLI/dyslexia) to their typically
      developing grade-matched peers. Results of the study revealed that children with
      SLI performed similarly to their typically developing peers on a single-word
      spelling task. Alternatively, those with dyslexia and SLI/dyslexia evidenced poor
      spelling accuracy. Errors made by both those with dyslexia and SLI/dyslexia were
      characterized by numerous phonologic, orthographic and semantic errors.
      Cumulative results support the hypothesis that word reading accuracy, not oral
      language, is associated with spelling performance in typically developing school
      age children and their peers with SLI and dyslexia. Findings are provided as
      further support for the notion that SLI and dyslexia are distinct, yet co-morbid,
      developmental disorders.

PMID- 22876770
TI  - Relationship between kinematics, F2 slope and speech intelligibility in
      dysarthria due to cerebral palsy.
AB  - A multimodal approach combining acoustics, intelligibility ratings,
      articulography and surface electromyography was used to examine the
      characteristics of dysarthria due to cerebral palsy (CP). CV syllables were
      studied by obtaining the slope of F2 transition during the diphthong, tongue-jaw
      kinematics during the release of the onset consonant, and the related submental
      muscle activities and relating these measures to speech intelligibility. The
      results show that larger reductions of F2 slope are correlated with lower
      intelligibility in CP-related dysarthria. Among the three speakers with CP, the
      speaker with the lowest F2 slope and intelligibility showed smallest tongue
      release movement and largest jaw opening movement. The other two speakers with CP
      were comparable in the amplitude and velocity of tongue movements, but one
      speaker had abnormally prolonged jaw movement. The tongue-jaw coordination
      pattern found in the speakers with CP could be either compensatory or subject to
      an incompletely developed oromotor control system.

PMID- 22876771
TI  - Vitamin A and vaccination.

PMID- 22876772
TI  - SARS-CoV regulates immune function-related gene expression in human monocytic
      cells.
AB  - Severe acute respiratory syndrome (SARS) is characterized by acute respiratory
      distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are
      the key players in the pathogenesis of SARS. In this study, we compared the
      transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells
      against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted
      from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after
      infection, and the gene expression was profiled in oligonucleotide-based
      microarrays. Analysis of immune-related gene expression profiles showed that at
      24 h after SARS-CoV infection: (1) IFN-alpha/beta-inducible and
      cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related
      genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor
      related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon
      related, and fibrosis-related genes were differentially regulated. These results
      elucidate that SARS-CoV infection regulates immune-related genes in
      monocytes/macrophages, which may be important to the pathogenesis of SARS.

PMID- 22876773
TI  - Hemokinin-1 as an adjuvant molecule enhancing humoral and memory responses to
      HBsAg DNA vaccination.
AB  - Incorporation of molecular adjuvants into DNA vaccines is often used to improve
      the induction of immune responses, but few approaches aim to specifically
      activate B cells for an enhanced humoral response only. Hemokinin-1 (HK-1) is a
      factor that activates B cells for proliferation, survival, differentiation into
      plasma cells, and Ab production. Therefore, we investigated if it may be used as
      a molecular adjuvant for DNA vaccines to elicit strong humoral and memory
      responses. The HK-1 coding sequence was sub-cloned as single or triple copies in
      frame downstream of S2 HBsAg in the proVAX/S2 construct. Compared to mice
      immunized with proVAX/S2 or proVAX/S2-HK-1, proVAX/S2-3HK-1 induced a higher
      level of IgG production, a higher percentage of differentiated antibody-secreting
      plasma cells, and a higher level of T-cell proliferation. Furthermore, a higher
      proportion of B cells had the B220(+)CD27(+) phenotype in these groups, and
      specific antigen re-challenge induced a higher level of total IgG production 60 d
      after the last immunization, suggesting that the use of HK-1 as an adjuvant
      promoted immunological memory. Taken together, these results suggest that using
      HK-1 as an adjuvant molecule could enhance the immunogenicity of HBsAg DNA
      vaccines, and result in stronger humoral and memory responses. Therefore, HK-1
      may lead to the development of a novel humoral-biased molecular adjuvant for an
      HBsAg DNA vaccine against hepatitis B infection.

PMID- 22876775
TI  - Lymphangioma circumscriptum in the scrotum: a case report.
AB  - INTRODUCTION: Lymphangioma circumscriptum is a rare benign skin disorder
      involving hamartomatous lymphatic malformation of deep dermal and subcutaneous
      lymphatic channels. It is a therapeutic challenge for the dermatologist when it
      occurs at common sites such as axilla, shoulder, groin and buttocks and a
      diagnostic challenge for the surgeon when it occurs at rare sites such as the
      scrotum. Surgical treatment is the most commonly used method to treat scrotal
      lymphangioma circumscriptum but there are high rates of recurrence. CASE
      PRESENTATION: We report the case of a 30-year-old Pakistani man who presented
      with scrotal swelling which was clinically misinterpreted as an infectious
      disorder. Later on re-resection of deeper tissue was performed to prevent
      recurrence. He is still being followed-up on a regular basis. CONCLUSION:
      Awareness of the occurrence of lymphangioma circumscriptum in the scrotum in
      adult men without prior disease is mandatory to avoid missing the diagnosis and
      to ensure proper treatment.

PMID- 22876776
TI  - The effect of core decompression on local expression of BMP-2, PPAR-gamma and
      bone regeneration in the steroid-induced femoral head osteonecrosis.
AB  - BACKGROUND: To investigate the efficacy of the sole core decompression surgery
      for the treatment of steroid-induced femoral head osteonecrosis. METHODS: The
      model was established by administration of steroids in combination with horse
      serum. The rabbits with bilateral femoral head osteonecrosis were randomly
      selected to do the one side of core decompression. The other side was used as the
      sham. Quantitative RT-PCR and western blot techniques were used to measure the
      local expression of BMP-2 and PPAR-gamma. Bone tissues from control and operation
      groups were histologically analyzed by H&E staining. The comparisons of the local
      expression of BMP-2 and PPAR-gamma and the bone regeneration were further
      analyzed between different groups at each time point. RESULTS: The expression of
      BMP-2 in the osteonecrosis femoral head with or without decompression was
      significantly lower than that in normal animals. BMP-2 expression both showed the
      decreasing trend with the increased post-operation time. No significant
      difference of BMP-2 expression occurred between femoral head osteonecrosis with
      and without decompression. The PPAR-gamma expression in the femoral head
      osteonecrosis with and without core decompression both was significantly higher
      than that in control. Its expression pattern showed a significantly increased
      trend with increased the post-operation time. However, there was no significant
      difference of PPAR-gamma expression between the femoral head osteonecrosis with
      and without decompression at each time point. Histopathological analysis revealed
      that new trabecular bone and a large number of osteoblasts were observed in the
      steroid-induced femoral head osteonecrosis with lateral decompression at 8 weeks
      after surgery, but there still existed trabecular bone fractures and bone
      necrosis. CONCLUSIONS: Although decompression takes partial effect in promoting
      bone regeneration in the early treatment of femoral head osteonecrosis, such an
      effect does not significantly improve or reverse the pathological changes of
      femoral head necrosis. Thus, the long-term effect of core decompression in the
      treatment of steroid-induced femoral head osteonecrosis is not satisfactory.

PMID- 22876774
TI  - 25(OH)D3 and cardiovascular risk factors in female nonhuman primates.
AB  - OBJECTIVE: To determine if interindividual differences in plasma concentrations
      of 25-hydroxyvitamin D(3) (25(OH)D(3)) have pathophysiologic significance, we
      evaluated a cohort of female monkeys, seeking to identify associations with
      clinically relevant cardiovascular risk factors, including age, abdominal obesity
      (waist circumference), and high-density lipoprotein cholesterol (HDL-C). METHODS:
      One hundred fifty-five female vervet monkeys (Chlorocebus aethiops sabaeus) aged
      3-25 years consumed a typical western diet for 7-8 weeks that provided a woman's
      equivalent of approximately 1000 IU/day of vitamin D(3). Measurements of vitamin
      D(3) and HDL-C concentrations, as well as waist circumference, were obtained.
      RESULTS: Among young monkeys (aged 3-5 years), compared to older monkeys (aged 16
      25 years), the mean plasma 25(OH)D(3) concentrations were 82.3+/-3.2 ng/mL and
      58.6+/-2.9 ng/mL (p<0.0001), respectively. Plasma 25(OH)D(3) concentrations had a
      range of 19.6-142.0 ng/mL (mean+/-standard error [SE] 66.4+/-1.7 ng/mL).
      25(OH)D(3) concentrations were inversely associated with age (p<0.0001) and waist
      circumference (p=0.016) and were positively correlated with HDL-C (p=0.01).
      However, when statistically controlling for age, none of these relationships
      remained significant. CONCLUSIONS: Higher plasma concentrations of 25(OH)D(3)
      were associated with more favorable cardiovascular risk factors, with inverse
      associations observed between 25(OH)D(3) and abdominal obesity, HDL-C, and age.
      These associations were no longer significant when controlling for age.

PMID- 22876777
TI  - High prevalence of Arginine to Glutamine substitution at 98, 141 and 162
      positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among
      Indians.
AB  - BACKGROUND: Troponin I (TNNI3) is the inhibitory subunit of the thin filament
      regulatory complex Troponin, which confers calcium-sensitivity to striated muscle
      actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in
      hypertrophic cardiomyopathy patients (HCM). However, the frequencies of mutations
      and associated clinical presentation have not been established in cardiomyopathy
      patients of Indian origin, hence we have undertaken this study. METHODS: We have
      sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in
      101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls,
      inhabited in the same geographical region of southern India. RESULTS: Our study
      revealed a total of 16 mutations. Interestingly, we have observed Arginine to
      Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM
      patients with family history of sudden cardiac death. The novel R98Q was observed
      in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q
      mutation was observed in two familial cases of severe asymmetric septal
      hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean
      septal thickness of 29 mm, and have also consists of allelic heterogeneity by
      means of having one more synonymous (E179E) mutation at g.4797: G -> A: in the
      same exon 7, which replaces a very frequent codon (GAG: 85%) with a rare codon
      (GAA: 14%). Screening for R162Q mutation in all the available family members
      revealed its presence in 9 individuals, including 7 with allelic heterogeneity
      (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs,
      (g.2653; G -> A and g.4003 C -> T) exclusively in HCM, and in silico analysis of
      these SNPs have predicted to cause defect in recognition/binding sites for
      proteins responsible for proper splicing. CONCLUSION: Our study has provided
      valuable information regarding the prevalence of TNNI3 mutations in Indian HCM
      patients and its risk assessment, these will help in genetic counseling and to
      adopt appropriate treatment strategies.

PMID- 22876779
TI  - Prevention of venous thromboembolism with new oral anticoagulants versus standard
      pharmacological treatment in acute medically ill patients: a systematic review
      and meta-analysis.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a common and potentially avoidable
      cause of morbidity and mortality in patients hospitalized for acute medical
      illness. OBJECTIVE: Our objective was to conduct a systematic review of studies
      that assessed the efficacy and safety of new oral anticoagulant (OAC) drugs
      versus standard pharmacological drugs and/or placebo in prevention of VTE in
      acute medically ill patients. METHODS: PubMed.org and ClinicalTrials.gov
      databases were searched to identify studies that evaluated the efficacy and
      safety of a new OAC versus the standard pharmacological treatment and/or placebo
      in the prevention of VTE in medically ill patients. Relative risks (RR), weighted
      means and 95% CIs were calculated. Statistical heterogeneity was evaluated using
      Chi2 and I2 statistics. Two studies were included in the meta-analysis. The
      primary outcome in both studies was the composite of VTE-related death,
      symptomatic non-fatal pulmonary embolism (PE), symptomatic deep venous thrombosis
      (DVT) and asymptomatic proximal DVT. Both studies compared a factor (F)Xa
      inhibitor with enoxaparin in standard short-term thromboprophylaxis followed by a
      period where the FXa inhibitor was compared with placebo as prolonged
      thromboprophylaxis in medically ill patients. The primary major safety outcome in
      both studies was a composite of treatment-related major bleeding and clinically
      relevant non-major bleeding. A total of 14 629 patients were randomized. RESULTS:
      Compared with subjects treated with enoxaparin followed by placebo, the RR of the
      primary outcome during the prolonged treatment period was 0.79 (95% CI 0.66,
      0.94), the RR for the primary outcome during the first short-term treatment
      period was 1.03 (95% CI 0.81, 1.31). For major bleeding during the prolonged
      treatment period, the RR was 2.69 (95% CI 1.65, 4.39) for patients treated with
      an FXa inhibitor compared with enoxaparin/placebo. For major bleeding during the
      shorter treatment period, the RR was 2.01 (95% CI 1.10, 3.65) in favour of
      enoxaparin. CONCLUSION: In acute medically ill patients, prolonged
      thromboprophylaxis with an oral FXa inhibitor is more protective than regular
      short-term treatment with enoxaparin. However, treatment with FXa inhibitors is
      significantly associated with major bleeding, both in long- and short-term
      treatment compared with enoxaparin.

PMID- 22876780
TI  - Mechanical work and physiological responses to simulated cross country mountain
      bike racing.
AB  - The purpose was to assess the mechanical work and physiological responses to
      cross country mountain bike racing. Participants (n = 7) cycled on a cross
      country track at race speed whilst VO2, power, cadence, speed, and geographical
      position were recorded. Mean power during the designated start section (68.5 +/-
      5.5 s) was 481 +/- 122 W, incurring an O2 deficit of 1.58 +/- 0.67 L - min(-1)
      highlighting a significant initial anaerobic (32.4 +/- 10.2%) contribution.
      Complete lap data produced mean (243 +/- 12 W) and normalised (279 +/- 15 W)
      power outputs with 13.3 +/- 6.1 and 20.7 +/- 8.3% of time spent in high force
      high velocity and high force-low velocity, respectively. This equated to,
      physiological measures for %VO(2max) (77 +/- 5%) and % HR(max) (93 +/- 2%).
      Terrain (uphill vs downhill) significantly (P < 0.05) influenced power output
      (70.9 +/- 7.5 vs. 41.0 +/- 9.2% W(max)),the distribution of low velocity force
      production, VO2 (80 +/- 1.7 vs. 72 +/- 3.7%) and cadence (76 + 2 vs. 55 +/- 4
      rpm) but not heart rate (93.8 +/- 2.3 vs. 91.3 +/- 0.6% HR(max)) and led to a
      significant difference between anaerobic contribution and terrain (uphill, 6.4 +/
      3.0 vs. downhill, 3.2 +/- 1.8%, respectively) but not aerobic energy
      contribution. Both power and cadence were highly variable through all sections
      resulting in one power surge every 32 s and a supra-maximal effort every 106 s.
      The results show that cross country mountain bike racing consists of
      predominantly low velocity pedalling with a large high force component and when
      combined with a high oscillating work rate, necessitates high aerobic energy
      provision, with intermittent anaerobic contribution. Additional physical stress
      during downhill sections affords less recovery emphasised by physiological
      variables remaining high throughout.

PMID- 22876781
TI  - Translational effects on electronic and nuclear ring currents.
AB  - In previous works, it was predicted that electronic and nuclear ring currents in
      degenerate excited states of atomic and molecular systems persist after the end
      of driven circularly polarized atto- or femtosecond laser pulses on relatively
      long time scales, often on pico- or nanosecond time scales, before spontaneous
      emission occurs. Although this conclusion is true in the center of mass frame, it
      is not true in the laboratory frame, where the translation has to be considered.
      In this theoretical work, the analytic formulas for the ring current densities,
      electric ring currents, mean ring current radii, and induced magnetic fields at
      the ring center, depending on the translational wavepacket widths, are derived.
      It shows that the ring currents and the corresponding induced magnetic fields in
      the laboratory frame persist on shorter timecales due to spreading of
      translational wavepackets. The electronic ring currents in 2p(+/-) orbitals of
      the hydrogen-like systems decay on the femtosecond time scale, but the
      corresponding nuclear ring currents with giant induced magnetic fields (for
      example up to 0.54 MT for (7)Li(2+)) and very small mean ring current radii on
      the femtometer scale decay on the very short, zeptosecond time scale, according
      to the Heisenberg uncertainty principle. The theory is also applied to ring
      currents in many-electron atoms and ions as well as to nuclear ring currents in
      pseudorotating molecules. For example, in the first triply degenerate
      pseudorotational states |v(1)l(+/-1)> of the tetrahedral molecule OsH(4), the
      ring currents of the heavy central nucleus Os decay on the attosecond time scale.

PMID- 22876782
TI  - Scanning electrochemical microscopy monitoring in microcantilever platforms.
AB  - The deflection of cantilever systems may be performed by an indirect
      electrochemical method that consists of measuring the local cantilever activity
      and deflection in a feedback generation-collection configuration of the SECM.
      This is illustrated during the electrochemically assisted adsorption of Br onto a
      gold-coated cantilever, either in its pristine state or previously coated with a
      thin organic barrier. It is further extended to the adsorption of an antibody in
      a heterogeneous immunoassay at an allergen-coated microcantilever platform. In
      both reactions, the cantilever deflection is qualitatively detected from the SECM
      tip current measurement and a quantitative estimate is obtained through modeling.
      This electroanalytical strategy provides an alternative approach to standard
      optical detection. It can overcome some limitations of the optical method by
      allowing electrochemical characterization of nonconductive cantilevers and
      appropriate use for closed systems.

PMID- 22876783
TI  - The role of the C8 proton of ATP in the catalysis of shikimate kinase and
      adenylate kinase.
AB  - BACKGROUND: It has been demonstrated that the adenyl moiety of ATP plays a direct
      role in the regulation of ATP binding and/or phosphoryl transfer within a range
      of kinase and synthetase enzymes. The role of the C8-H of ATP in the binding
      and/or phosphoryl transfer on the enzyme activity of a number of kinase and
      synthetase enzymes has been elucidated. The intrinsic catalysis rate mediated by
      each kinase enzyme is complex, yielding apparent KM values ranging from less than
      0.4 MUM to more than 1 mM for ATP in the various kinases. Using a combination of
      ATP deuterated at the C8 position (C8D-ATP) as a molecular probe with site
      directed mutagenesis (SDM) of conserved amino acid residues in shikimate kinase
      and adenylate kinase active sites, we have elucidated a mechanism by which the
      ATP C8-H is induced to be labile in the broader kinase family. We have
      demonstrated the direct role of the C8-H in the rate of ATP consumption, and the
      direct role played by conserved Thr residues interacting with the C8-H. The
      mechanism by which the vast range in KM might be achieved is also suggested by
      these findings. RESULTS: We have demonstrated the mechanism by which the enzyme
      activities of Group 2 kinases, shikimate kinase (SK) and adenylate kinase 1
      (AK1), are controlled by the C8-H of ATP. Mutations of the conserved threonine
      residues associated with the labile C8-H cause the enzymes to lose their
      saturation kinetics over the concentration range tested. The relationship between
      the role C8-H of ATP in the reaction mechanism and the ATP concentration as they
      influence the saturation kinetics of the enzyme activity is also shown. The SDM
      clearly identified the amino acid residues involved in both the catalysis and
      regulation of phosphoryl transfer in SK and AK1 as mediated by C8H-ATP.
      CONCLUSIONS: The data outlined serves to demonstrate the "push" mechanism
      associated with the control of the saturation kinetics of Group 2 kinases
      mediated by ATP C8-H. It is therefore conceivable that kinase enzymes achieve the
      observed 2,500-fold variation in KM through a combination of the various
      conserved "push" and "pull" mechanisms associated with the release of C8-H, the
      proton transfer cascades unique to the class of kinase in question and the
      resultant/concomitant creation of a pentavalent species from the gamma-phosphate
      group of ATP. Also demonstrated is the interplay between the role of the C8-H of
      ATP and the ATP concentration in the observed enzyme activity. The lability of
      the C8-H mediated by active site residues co-ordinated to the purine ring of ATP
      therefore plays a significant role in explaining the broad KM range associated
      with kinase steady state enzyme activities.

PMID- 22876784
TI  - Toxicokinetics of methyleugenol in F344 rats and B6C3F1 mice.
AB  - 1. Methyleugenol (MEG) has been used as a flavouring agent in food, as a
      fragrance in cosmetic products, and as an insect attractant. MEG was carcinogenic
      in both rats and mice following gavage administration. In this study we
      investigated plasma toxicokinetics of MEG in F344 rats and B6C3F1 mice of both
      sexes following single gavage (37, 75, or 150 mg/kg) and intravenous (IV) (37
      mg/kg) administration. 2. Following IV administration, MEG was rapidly
      distributed and cleared from the systemic circulation in both species and sexes.
      Absorption of MEG was rapid following gavage administration with secondary peaks
      in the plasma MEG concentration-versus-time profiles. C(max) and AUC(T) increased
      and the clearance decreased greater than proportional to the dose in rats and
      mice of both sexes. In general, rats had higher internal exposure to MEG than
      mice. 3. The results for AUC(T) and clearance suggest that perhaps the metabolism
      of MEG is saturated at higher doses tested in this study. Absolute
      bioavailability following gavage administration of 37 mg/kg was low in both rats
      (~4%) and mice (7-9%) of both sexes indicating extensive first-pass metabolism.
      There was no sex difference in plasma toxicokinetics of MEG following gavage
      administration both in rats and mice.

PMID- 22876785
TI  - Hybridizing energy conversion and storage in a mechanical-to-electrochemical
      process for self-charging power cell.
AB  - Energy generation and energy storage are two distinct processes that are usually
      accomplished using two separated units designed on the basis of different
      physical principles, such as piezoelectric nanogenerator and Li-ion battery; the
      former converts mechanical energy into electricity, and the latter stores
      electric energy as chemical energy. Here, we introduce a fundamental mechanism
      that directly hybridizes the two processes into one, in which the mechanical
      energy is directly converted and simultaneously stored as chemical energy without
      going through the intermediate step of first converting into electricity. By
      replacing the polyethylene (PE) separator as for conventional Li battery with a
      piezoelectric poly(vinylidene fluoride) (PVDF) film, the piezoelectric potential
      from the PVDF film as created by mechanical straining acts as a charge pump to
      drive Li ions to migrate from the cathode to the anode accompanying charging
      reactions at electrodes. This new approach can be applied to fabricating a self
      charging power cell (SCPC) for sustainable driving micro/nanosystems and personal
      electronics.

PMID- 22876786
TI  - Detecting phylogenetic signals in eukaryotic whole genome sequences.
AB  - Whole genome sequences are a rich source of molecular data, with a potential for
      the discovery of novel evolutionary information. Yet, many parts of these
      sequences are not known to be under evolutionary pressure and, thus, are not
      conserved. Furthermore, a good model for whole genome evolution does not exist.
      Consequently, it is not a priori clear if a meaningful phylogenetic signal exists
      and can be extracted from the sequences as a whole. Indeed, very few phylogenies
      were reconstructed based on these sequences. Prior to this work, only two
      reconstruction methods were applied to large eukaryotic genomes: the K(r) method
      (Haubold et al., 2009), which was applied to genomes of rather small diversity
      (Drosophila species), and the feature frequency profile method (Sims et al.,
      2009a), which was applied to genomes of moderate diversity (mammals). We
      investigate the whole genome-based phylogenetic reconstruction question with
      respect to a much wider taxonomic sample. We apply K(r), FFP, and an alternative
      alignment-free method, the average common subsequence (ACS) (Ulitsky et al.,
      2006), to 24 multicellular eukaryotes (vertebrates, invertebrates, and plants).
      We also apply ACS to the proteome sequences of these 24 taxa. We compare the
      resulting trees to a standard reference, the National Center for Biotechnology
      Information (NCBI) taxonomy tree. Trees produced by ACS(AA), based on proteomes,
      are in complete agreement with the NCBI tree. For the genome-based
      reconstruction, ACS(DNA) produces trees whose agreement with the NCBI tree is
      excellent to very good for divergence times up to 800 million years ago, medium
      at 1 billion years ago, and poor at 1.6 billion years ago. We conclude that whole
      genomes do carry a clear phylogenetic signal, yet this signal "saturates" with
      longer divergence times. Furthermore, from the few existing methods, ACS is best
      capable of detecting this signal.

PMID- 22876787
TI  - Supervised protein family classification and new family construction.
AB  - The goal of protein family classification is to group proteins into families so
      that proteins within the same family have common function or are related by
      ancestry. While supervised classification algorithms are available for this
      purpose, most of these approaches focus on assigning unclassified proteins to
      known families but do not allow for progressive construction of new families from
      proteins that cannot be assigned. Although unsupervised clustering algorithms are
      also available, they do not make use of information from known families. By
      computing similarities between proteins based on pairwise sequence comparisons,
      we develop supervised classification algorithms that achieve improved accuracy
      over previous approaches while allowing for construction of new families. We show
      that our algorithm has higher accuracy rate and lower mis-classification rate
      when compared to algorithms that are based on the use of multiple sequence
      alignments and hidden Markov models, and our algorithm performs well even on
      families with very few proteins and on families with low sequence similarity. A
      software program implementing the algorithm (SClassify) is available online
      (http://faculty.cse.tamu.edu/shsze/sclassify).

PMID- 22876788
TI  - Using noise for model-testing.
AB  - For realistic models in molecular biology, you need to consider the noise in the
      cellular and intracellular environments. In this article, we present a novel
      approach for testing the validity of nonlinear models representing a biological
      system affected by noise. Our approach is based on results by Kushner and
      Oksendal and uses computational techniques that rely on efficient solvers. By
      providing analytically upper bounds for the exit probability of solution
      trajectories of a system from a particular set in the phase space, we can compare
      measurement data with this prediction and try to invalidate models with certain
      parameter values or noise properties. Thus, our approach complements the usual
      methods that are based on deterministic models. It is particularly useful in the
      field of reverse engineering in systems biology, when one seeks to determine
      model parameters and noise properties as we show in the Results section, where we
      applied the approach to examples of increasing complexity and to the Hog1
      signalling pathway.

PMID- 22876789
TI  - Recovering independent associations in genetics: a comparison.
AB  - In genetics, it is often of interest to discover single nucleotide polymorphisms
      (SNPs) that are directly related to a disease, rather than just being associated
      with it. Few methods exist, however, for addressing this so-called "true sparsity
      recovery" issue. In a thorough simulation study, we show that for moderate or low
      correlation between predictors, lasso-based methods perform well at true sparsity
      recovery, despite not being specifically designed for this purpose. For large
      correlations, however, more specialized methods are needed. Stability selection
      and direct effect testing perform well in all situations, including when the
      correlation is large.

PMID- 22876790
TI  - Fabrication of porous silicon by metal-assisted etching using highly ordered gold
      nanoparticle arrays.
AB  - A simple method for the fabrication of porous silicon (Si) by metal-assisted
      etching was developed using gold nanoparticles as catalytic sites. The etching
      masks were prepared by spin-coating of colloidal gold nanoparticles onto Si. An
      appropriate functionalization of the gold nanoparticle surface prior to the
      deposition step enabled the formation of quasi-hexagonally ordered arrays by self
      assembly which were translated into an array of pores by subsequent etching in HF
      solution containing H2O2. The quality of the pattern transfer depended on the
      chosen preparation conditions for the gold nanoparticle etching mask. The
      influence of the Si surface properties was investigated by using either
      hydrophilic or hydrophobic Si substrates resulting from piranha solution or HF
      treatment, respectively. The polymer-coated gold nanoparticles had to be
      thermally treated in order to provide a direct contact at the metal/Si interface
      which is required for the following metal-assisted etching. Plasma treatment as
      well as flame annealing was successfully applied. The best results were obtained
      for Si substrates which were flame annealed in order to remove the polymer matrix
      - independent of the substrate surface properties prior to spin-coating
      (hydrophilic or hydrophobic). The presented method opens up new resources for the
      fabrication of porous silicon by metal-assisted etching. Here, a vast variety of
      metal nanoparticles accessible by well-established wet-chemical synthesis can be
      employed for the fabrication of the etching masks.

PMID- 22876791
TI  - Protective effect of the Japanese traditional medicine juzentaihoto on
      myelosuppression induced by the anticancer drug TS-1 and identification of a
      potential biomarker of this effect.
AB  - BACKGROUND: TS-1 is an oral anticancer drug containing a 5-fluorouracil
      derivative (Tegafur) that is widely used in Japan for the treatment of cancer,
      especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be
      discontinued because of leukopenia. If it were possible to predict the
      development of bone marrow suppression before the white blood cell (WBC) count
      had actually decreased, treatment could be improved by strict dosage control
      and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto
      (JTT), a traditional Japanese medicine (Kampo), has been reported to activate
      hematopoiesis and reduce the side effects associated with chemotherapy and
      radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating
      myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that
      reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression
      using a proteomics approach. METHODS: Ten mg/kg of TS-1 was administered to
      Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and
      ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma
      samples were analyzed using surface-enhanced laser desorption/ionization time-of
      flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI
      profiling was identified using a combination of cation exchange spin column
      purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. RESULTS: After
      administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio
      were observed at days 5 and 3, respectively. JTT treatment improved WBC count on
      day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three
      protein peaks that had increased on day 3 after treatment with TS-1 but remained
      unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was
      further investigated and identified as a specific C-terminal fragment of albumin.
      CONCLUSION: This study indicates that bone marrow suppression by treatment with
      TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment
      of albumin was identified as a candidate biomarker for predicting TS-1-induced
      myelosuppression. However, the sensitivity and specificity of the biomarker
      candidate must be validated in future clinical studies.

PMID- 22876792
TI  - Full incorporation of StratticeTM Reconstructive Tissue Matrix in a reinforced
      hiatal hernia repair: a case report.
AB  - INTRODUCTION: A non-cross-linked porcine acellular dermal matrix was used to
      reinforce an esophageal hiatal hernia repair. A second surgery was required 11
      months later to repair a slipped Nissen; this allowed for examination of the
      hiatal hernia repair and showed the graft to be well vascularized and fully
      incorporated. CASE PRESENTATION: A 71-year-old Caucasian woman presented with
      substernal burning and significant dysphagia. An upper gastrointestinal series
      revealed a type III complex paraesophageal hiatal hernia. She underwent
      laparoscopic surgery to repair a hiatal hernia that was reinforced with a
      xenograft (StratticeTM Reconstructive Tissue Matrix, LifeCell, Branchburg, NJ,
      USA) along with a Nissen fundoplication. A second surgery was required to repair
      a slipped Nissen; this allowed for examination of the hiatal repair and graft
      incorporation 11 months after the initial surgery. CONCLUSION: In this case, a
      porcine acellular dermal matrix was an effective tool to reinforce the crural
      hiatal hernia repair. The placement of the mesh and method of fixation are
      believed to be crucial to the success of the graft. It was found to be well
      vascularized 11 months after the original placement with no signs of erosion,
      stricture, or infection. Further studies and long-term follow-up are required to
      support the findings of this case report.

PMID- 22876793
TI  - Parametric dependence in model epidemics. II: Non-contact rate-related
      parameters.
AB  - In a previous paper, we discussed the bifurcation structure of SEIR equations
      subject to seasonality. There, the focus was on parameters that affect
      transmission: the mean contact rate, beta(0), and the magnitude of seasonality,
      epsilon(B). Using numerical continuation and brute force simulation, we
      characterized a global pattern of parametric dependence in terms of subharmonic
      resonances and period-doublings of the annual cycle. In the present paper, we
      extend this analysis and consider the effects of varying non-contact-related
      parameters: periods of latency, infection and immunity, and rates of mortality
      and reproduction, which, following the usual practice, are assumed to be equal.
      The emergence of several new forms of dynamical complexity notwithstanding, the
      pattern previously reported is preserved. More precisely, the principal effect of
      varying non-contact related parameters is to displace bifurcation curves in the
      beta(0)-epsilon(B) parameter plane and to expand or contract the regions of
      resonance and period-doubling they delimit. Implications of this observation with
      respect to modeling real-world epidemics are considered.

PMID- 22876794
TI  - The ideal free distribution as an evolutionarily stable strategy.
AB  - We examine the evolutionary stability of strategies for dispersal in
      heterogeneous patchy environments or for switching between discrete states (e.g.
      defended and undefended) in the context of models for population dynamics or
      species interactions in either continuous or discrete time. There have been a
      number of theoretical studies that support the view that in spatially
      heterogeneous but temporally constant environments there will be selection
      against unconditional, i.e. random, dispersal, but there may be selection for
      certain types of dispersal that are conditional in the sense that dispersal rates
      depend on environmental factors. A particular type of dispersal strategy that has
      been shown to be evolutionarily stable in some settings is balanced dispersal, in
      which the equilibrium densities of organisms on each patch are the same whether
      there is dispersal or not. Balanced dispersal leads to a population distribution
      that is ideal free in the sense that at equilibrium all individuals have the same
      fitness and there is no net movement of individuals between patches or states. We
      find that under rather general assumptions about the underlying population
      dynamics or species interactions, only such ideal free strategies can be
      evolutionarily stable. Under somewhat more restrictive assumptions (but still in
      considerable generality), we show that ideal free strategies are indeed
      evolutionarily stable. Our main mathematical approach is invasibility analysis
      using methods from the theory of ordinary differential equations and nonnegative
      matrices. Our analysis unifies and extends previous results on the evolutionary
      stability of dispersal or state-switching strategies.

PMID- 22876795
TI  - Periodicity, persistence, and collapse in host-parasitoid systems with egg
      limitation.
AB  - There is an emerging consensus that parasitoids are limited by the number of eggs
      which they can lay as well as the amount of time they can search for their hosts.
      Since egg limitation tends to destabilize host-parasitoid dynamics, successful
      control of insect pests by parasitoids requires additional stabilizing mechanisms
      such as heterogeneity in the distribution of parasitoid attacks and host density
      dependence. To better understand how egg limitation, search limitation,
      heterogeneity in parasitoid attacks, and host density-dependence influence host
      parasitoid dynamics, discrete time models accounting for these factors are
      analyzed. When parasitoids are purely egg-limited, a complete anaylsis of the
      host-parasitoid dynamics are possible. The analysis implies that the parasitoid
      can invade the host system only if the parasitoid's intrinsic fitness exceeds the
      host's intrinsic fitness. When the parasitoid can invade, there is a critical
      threshold, CV*>1, of the coefficient of variation (CV) of the distribution of
      parasitoid attacks that determines that outcome of the invasion. If parasitoid
      attacks sufficiently aggregated (i.e., CV>CV*), then the host and parasitoid
      coexist. Typically (in a topological sense), this coexistence is shown to occur
      about a periodic attractor or a stable equilibrium. If the parasitoid attacks are
      sufficiently random (i.e. CV<CV*), then the parasitoid drives the host to
      extinction. When parasitoids are weakly search-limited as well as egg-limited,
      coexistence about a global attractor occurs even if CV<CV*. However, numerical
      simulations suggest that the nature of this attractor depends critically on
      whether CV<1 or CV>1. When CV<1, the parasitoid exhibits highly oscillatory
      dynamics. Alternatively, when parasitoid attacks are sufficiently aggregated but
      not overly aggregated (i.e. CV>1 but close to 1), the host and parasitoid coexist
      about a stable equilibrium with low host densities. The implications of these
      results for classical biological control are discussed.

PMID- 22876797
TI  - Steric effects compete with aryne distortion to control regioselectivities of
      nucleophilic additions to 3-silylarynes.
AB  - We report an experimental and computational study of 3-silylarynes. The addition
      of nucleophiles yield ortho-substituted products as a result of aryne distortion,
      but meta-substituted products form predominately when the nucleophile is large.
      Computations correctly predict the preferred site of attack observed in both
      nucleophilic addition and cycloaddition experiments. Nucleophilic additions to 3
      tert-butylbenzyne, which is not significantly distorted, give meta-substituted
      products.

PMID- 22876798
TI  - ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds
      with potential adverse reactions.
AB  - The article presents a Web-based platform for collecting and storing
      toxicological structural alerts from literature and for virtual screening of
      chemical libraries to flag potentially toxic chemicals and compounds that can
      cause adverse side effects. An alert is uniquely identified by a SMARTS template,
      a toxicological endpoint, and a publication where the alert was described.
      Additionally, the system allows storing complementary information such as name,
      comments, and mechanism of action, as well as other data. Most importantly, the
      platform can be easily used for fast virtual screening of large chemical
      datasets, focused libraries, or newly designed compounds against the
      toxicological alerts, providing a detailed profile of the chemicals grouped by
      structural alerts and endpoints. Such a facility can be used for decision making
      regarding whether a compound should be tested experimentally, validated with
      available QSAR models, or eliminated from consideration altogether. The alert
      based screening can also be helpful for an easier interpretation of more complex
      QSAR models. The system is publicly accessible and tightly integrated with the
      Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open
      and expandable: any registered OCHEM user can introduce new alerts, browse, edit
      alerts introduced by other users, and virtually screen his/her data sets against
      all or selected alerts. The user sets being passed through the structural alerts
      can be used at OCHEM for other typical tasks: exporting in a wide variety of
      formats, development of QSAR models, additional filtering by other criteria, etc.
      The database already contains almost 600 structural alerts for such endpoints as
      mutagenicity, carcinogenicity, skin sensitization, compounds that undergo
      metabolic activation, and compounds that form reactive metabolites and, thus, can
      cause adverse reactions. The ToxAlerts platform is accessible on the Web at
      http://ochem.eu/alerts, and it is constantly growing.

PMID- 22876799
TI  - Early preterm delivery due to placenta previa is an independent risk factor for a
      subsequent spontaneous preterm birth.
AB  - BACKGROUND: To determine whether patients with placenta previa who delivered
      preterm have an increased risk for recurrent spontaneous preterm birth. METHODS:
      This retrospective population based cohort study included patients who delivered
      after a primary cesarean section (n = 9983). The rate of placenta previa, its
      recurrence, and the risk for recurrent preterm birth were determined. RESULTS:
      Patients who had a placenta previa at the primary CS pregnancy had an increased
      risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm
      birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and
      these patients had a higher rate of recurrent preterm delivery than the rest of
      the study population (p < .001). Among patients with placenta previa in the
      primary CS pregnancy, those who delivered preterm had a higher rate of recurrent
      spontaneous preterm birth regardless of the location of their placenta in the
      subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients
      with who had a primary cesarean section, patients who had placenta previa and
      delivered preterm had an independent increased risk for recurrent preterm birth
      [OR of 3.6 (95% CI 1.5-8.5)]. CONCLUSIONS: Women with placenta previa, who
      deliver preterm, especially before 34 weeks of gestation, are at increased risk
      for recurrent spontaneous preterm birth regardless to the site of placental
      implantation in the subsequent pregnancy. Thus, strict follow up by high risk
      pregnancies specialist is recommended.

PMID- 22876800
TI  - Health of women after wartime deployments: correlates of risk for selected
      medical conditions among females after initial and repeat deployments to
      Afghanistan and Iraq, active component, U.S. Armed Forces.
AB  - Women account for approximately 10 percent of all U.S. military deployers to
      Afghanistan and Iraq. This analysis estimates the percentages of female deployers
      (n=154,548) who were affected by selected illnesses and injuries after first
      through third deployments to Iraq/Afghanistan in relation to age group, service
      branch, military occupation, marital status, pre-deployment medical history,
      "dwell time" prior to 2nd and 3rd deployments, and length of deployment. Of these
      factors, diagnosis of a condition before deployment was by far the strongest
      predictor of diagnosis of the condition after deployment. Durations of dwell
      times before repeat deployments were not strong predictors of post-deployment
      diagnoses of any of the conditions considered. For several conditions (e.g.,
      PTSD, disorders of joints, peripheral enthesopathies, infertility), the
      percentages of deployers diagnosed with the conditions sharply increased with
      deployment length. Post-deployment morbidity moderately increased with increasing
      numbers of deployments in the case of some conditions (e.g., PTSD, migraine,
      musculoskeletal disorders), but not others. The findings suggest that limiting
      wartime deployments to nine months may have broad beneficial effects on the post
      deployment health of female service members. However, limiting the number of
      wartime deployments and lengthening "dwell times" before repeat deployments would
      likely not have strong and broad beneficial effects on the health of female
      veterans. Further research to mitigate the effects of heavy loads and repetitive
      stresses on the musculoskeletal systems of combat deployed females is indicated.

PMID- 22876801
TI  - Acute pelvic inflammatory disease, active component, U.S. Armed Forces, 2002
      2011.
AB  - Pelvic inflammatory disease (PID) refers to a group of inflammatory disorders of
      the female upper genital tract caused by the spread from the lower genital tract
      of Chlamydia trachomatis and other organisms. PID can cause chronic pelvic pain,
      fallopian tube damage, infertility and ectopic pregnancy. Between January 2002
      and December 2011, 16,817 female service members met the surveillance case
      definition for acute PID. Incidence rates were stable at approximately 8 per
      1,000 person-years overall and 11 per 1,000 person-years among known high-risk
      sub-populations (i.e., women 17-24 years old, in the Army, and of black, non
      Hispanic race/ethnicity). Twenty-six women were diagnosed with PID within 10 days
      after medical evacuation from Iraq/Afghanistan. The proportion of servicewomen
      diagnosed with infertility subsequent to an incident diagnosis of acute PID
      increased during the period. Rates of PID are higher in the Army than the other
      Services. This may reflect differences in Service policies for chlamydia
      screening of new accessions.

PMID- 22876802
TI  - Ectopic pregnancy, active component, U.S. Armed Forces, 2002-2011.
AB  - Ectopic pregnancy (EP) is a rare adverse outcome in which a fertilized egg
      implants and develops outside of the uterus. Life-threatening cases of EP among
      deployed U.S. service members have been described. During 2002- 2011, among
      active component females younger than 49, 1,245 EPs were diagnosed and treated as
      indicated by diagnostic and procedure codes recorded in electronic medical
      records. Annual numbers of EPs ranged from 91 to 151. During the period EP
      affected 0.64 percent of all pregnancies, with higher proportions among
      servicewomen in their 30s and of black, non-Hispanic race/ ethnicity. As compared
      with civilians, service members had the same percentage of pregnancies that were
      ectopic but had lower proportions of EPs that were treated medically (with
      methotrexate) rather than surgically.

PMID- 22876803
TI  - Iron deficiency anemia, active component, U.S. Armed Forces, 2002-2011.
AB  - Iron deficiency anemia (IDA) is the most common cause of anemia in the United
      States, and it particularly affects women of child-bearing age and black, non
      Hispanic race/ethnicity. During the surveillance period there were 10,157
      incident  ("new") cases of IDA among active component service members; the
      overall incidence rate was 7.1 per 10,000 person-years. The annual incidence
      rates increased in both males and females during the period. Rates of IDA were
      higher among service members  who were female, in the youngest (<20 years) and
      oldest age groups (40+ years), and of black, non-Hispanic race/ethnicity. Most
      (85.3%) incident cases had no additional encounters for IDA one year or more
      after their incident encounter. The most common  diagnoses associated with IDA
      during the one year before or after the incidence dates of IDA were
      "gastrointestinal hemorrhage" (12.4%) in males and "disorders of menstruation and
      other abnormal bleeding from the female genital tract" (15.2%) in females. 
      Because IDA can adversely affect physical work capacity and cognitive
      functioning, health care providers should be alert to IDA among service members,
      particularly servicewomen, before intensive training activities and deployment.

PMID- 22876804
TI  - Historical snapshot: Dr. Mary E. Walker, Civil War surgeon, Medal of Honor
      recipient.

PMID- 22876805
TI  - Surveillance snapshot: Traumatic amputations among female service members, active
      and reserve components, U.S. Armed Forces, 2000-2011.

PMID- 22876806
TI  - Protective effect of grapefruit juice on the teratogenic and genotoxic damage
      induced by cadmium in mice.
AB  - In the present study, we injected pregnant mice at Day 7 of gestation with
      cadmium chloride (CC) (1.5 mg/kg) intraperitoneally and determined its effect on
      the frequency of fetal malformations at Day 17 of pregnancy. On the same day, we
      also determined the level of micronucleated polychromatic erythrocytes (MNPEs)
      and of micronucleated normochromatic erythrocytes (MNNEs) in blood cells of both
      the mothers and their fetuses. A significant increase in the number of
      malformations was found, mainly exencephaly, micrognathia, ablephary,
      microphthalmia, and clubfoot, as well as a significant increase in the amount of
      MNPEs and MNNEs. In addition, pregnant mice were administered grapefruit juice
      (GJ) orally from Days 0 to 17 of the experiment (from 200 to 800 MUL/g) to
      evaluate the potential of the juice in preventing the damage induced by CC. We
      found a dose-dependent decrease in the number of visceral and skeletal
      malformations, as well as in the number of MNPEs and MNNEs, in both the mothers
      and their fetuses. Furthermore, we determined the level of DNA oxidation by
      measuring levels of the adduct 8-hydroxy-2'-deoxyguanosine, and we found a
      significant increase in such level induced by CC; in contrast, there was a
      significant decrease when we added GJ. Therefore, the observed teratogenic and
      genotoxic protection can probably be related with the antioxidant potential of
      GJ.

PMID- 22876807
TI  - Coupling SIMD and SIMT architectures to boost performance of a phylogeny-aware
      alignment kernel.
AB  - BACKGROUND: Aligning short DNA reads to a reference sequence alignment is a
      prerequisite for detecting their biological origin and analyzing them in a
      phylogenetic context. With the PaPaRa tool we introduced a dedicated dynamic
      programming algorithm for simultaneously aligning short reads to reference
      alignments and corresponding evolutionary reference trees. The algorithm aligns
      short reads to phylogenetic profiles that correspond to the branches of such a
      reference tree. The algorithm needs to perform an immense number of pairwise
      alignments. Therefore, we explore vector intrinsics and GPUs to accelerate the
      PaPaRa alignment kernel. RESULTS: We optimized and parallelized PaPaRa on CPUs
      and GPUs. Via SSE 4.1 SIMD (Single Instruction, Multiple Data) intrinsics for x86
      SIMD architectures and multi-threading, we obtained a 9-fold acceleration on a
      single core as well as linear speedups with respect to the number of cores. The
      peak CPU performance amounts to 18.1 GCUPS (Giga Cell Updates per Second) using
      all four physical cores on an Intel i7 2600 CPU running at 3.4 GHz. The average
      CPU performance (averaged over all test runs) is 12.33 GCUPS. We also used OpenCL
      to execute PaPaRa on a GPU SIMT (Single Instruction, Multiple Threads)
      architecture. A NVIDIA GeForce 560 GPU delivered peak and average performance of
      22.1 and 18.4 GCUPS respectively. Finally, we combined the SIMD and SIMT
      implementations into a hybrid CPU-GPU system that achieved an accumulated peak
      performance of 33.8 GCUPS. CONCLUSIONS: This accelerated version of PaPaRa
      (available at http://www.exelixis-lab.org/software.html) provides a significant
      performance improvement that allows for analyzing larger datasets in less time.
      We observe that state-of-the-art SIMD and SIMT architectures deliver comparable
      performance for this dynamic programming kernel when the "competing programmer
      approach" is deployed. Finally, we show that overall performance can be
      substantially increased by designing a hybrid CPU-GPU system with appropriate
      load distribution mechanisms.

PMID- 22876808
TI  - Liposomes a vesicular nanocarrier: potential advancements in cancer chemotherapy.
AB  - The indispensable obligation behind the successful therapy of a disease is to
      deliver the effective drug/bioactive concentration with sustained release manner
      at the diseased organs without any exposure to the healthy tissues. Novel drug
      delivery systems increase the concentration and persistence of drug at the
      vicinity of the target site and thereby minimize the undesired side effects of
      the drug to the normal tissues of body. With advances in nanotechnology, several
      new drug delivery approaches have become available that may fulfil the
      requirement of safe and effective drug therapy. Among these techniques, vesicular
      drug-delivery systems, particularly liposomes, are under rigorous research for
      their applicability to deliver FDA-approved and newer drugs. Liposomes have been
      widely investigated as one of the most widely used nanocarriers in cancer therapy
      and have shown their potential in spatial and temporal release of bioactive
      agents for the effective treatment of various life-threatening diseases,
      including cancer. Various targeted and triggered-release approaches of bioactive
      substances using liposomes further improve the applicability of liposomes in
      cancer therapeutics. Thus, keeping these points in view, the present review has
      been focussed on application of liposomes for development of liposome technology
      and its novel applications for effective cancer therapy.

PMID- 22876809
TI  - Targeted breast cancer nanotherapeutics: options and opportunities with estrogen
      receptors.
AB  - Breast cancer is a multifarious and heterogeneous disease. Identification of
      molecular alterations of surface/intracellular proteins particularly involved in
      proliferation and growth of breast cancer cells provides opportunities for the
      development of new targets for therapy. Several ligands that are routinely
      employed in targeted delivery to breast cancer cells have been found to be
      immunogenic. Therefore, endogenous bioligands may serve as a better option, which
      may be bio-competent and non-immunogenic, including estrogens. Membrane
      associated estrogen binding sites are highly over-expressed in cancers of
      endocrine origin, such as breast. The selective high density of these receptor
      portals can be utilized for targeted breast cancer therapy. Numerous estrogen
      chemotherapeutic agent conjugates have been successfully utilized for targeted
      drug/DNA delivery. Recently, nanocarrier(s) anchored with estrogens as site
      directing ligands for the delivery of bioactive(s) have been exhaustively
      investigated for breast cancer therapy. This review presents a detail account of
      how estrogens, anti-estrogens, and their derivatives can be used for site
      specific delivery of bioactive(s) to breast cancer cells. The sequential
      emergence of various estrogen-anticancer drug conjugates is highlighted.
      Additionally, carrier systems that utilize estrogens/anti-estrogens as ligands
      for purpose-specific site-selective novel drug delivery platforms have been
      reviewed and revisited in terms of their realistic clinical applications in
      breast cancer treatment.

PMID- 22876810
TI  - Comments on "Accurate thermochemistry of hydrocarbon radicals via an extended
      generalized bond separation reaction scheme".

PMID- 22876811
TI  - Cervical spinal cord bullet fragment removal using a minimally invasive surgical
      approach: a case report.
AB  - INTRODUCTION: We present a case of penetrating gunshot injury to the high
      cervical spinal cord and describe a minimally invasive approach used for removal
      of the bullet fragment. We present this report to demonstrate technical
      feasibility of a minimally invasive approach to projectile removal. CASE
      PRESENTATION: An 18-year-old African-American man presented to our hospital with
      a penetrating gunshot injury to the high-cervical spine. The bullet lodged in the
      spinal cord at the C1 level and rendered our patient quadriplegic and dependent
      on a ventilator. For personal and forensic reasons, our patient and his family
      requested removal of the bullet fragment almost one year following the injury.
      Given the significant comorbidity associated with quadriplegia and ventilator
      dependency, a minimally invasive approach was used to limit the peri-operative
      complication risk and expedite recovery. Using a minimally invasive expandable
      retractor system and the aid of a microscope, the posterior arch of C1 was
      removed, the dura was opened, and the bullet fragment was successfully removed
      from the spinal cord. CONCLUSIONS: Here we describe a minimally invasive
      procedure demonstrating the technical feasibility of removing an intramedullary
      foreign object from the high-cervical spine. We do not suggest that the
      availability of minimally invasive procedures should lower the threshold or
      expand the indications for the removal of bullet fragments in the spinal canal.
      Rather, our objective is to expand the indications for minimally invasive
      procedures in an effort to reduce the morbidity and mortality associated with
      spinal procedures. In addition, this report may help to highlight the feasibility
      of this approach.

PMID- 22876812
TI  - Transgene therapy for rat anti-Thy1.1 glomerulonephritis via mesangial cell
      vector with a polyethylenimine/decorin nanocomplex.
AB  - Polyethylenimine (PEI), a cationic polymer, is one of the most efficient non
      viral vectors for transgene therapy. Decorin (DCN), a leucine-rich proteoglycan
      secreted by glomerular mesangial cells (MC), is a promising anti-fibrotic agent
      for the treatment of glomerulonephritis. In this study, we used PEI-DCN
      nanocomplexes with different N/P ratios to transfect MC in vitro and deliver the
      MC vector with PEI-DCN expressing into rat anti-Thy1.1 nephritis kidney tissue
      via injection into the left renal artery in vivo. The PEI-plasmid DNA complex at
      N/P 20 had the highest level of transfection efficiency and the lowest level of
      cytotoxicity in cultured MC. Following injection, the ex vivo gene was
      transferred successfully into the glomeruli of the rat anti-Thy1.1 nephritis
      model by the MC vector with the PEI-DCN complex. The exogenous MC with DCN
      expression was located mainly in the mesangium and the glomerular capillary. Over
      expression of DCN in diseased glomeruli could result in the inhibition of
      collagen IV deposition and MC proliferation. The pathological changes of rat
      nephritis were alleviated following injection of the vector. These findings
      demonstrate that the DCN gene delivered by the PEI-DNA nanocomplex with the MC
      vector is a promising therapeutic method for the treatment of glomerulonephritis.

PMID- 22876813
TI  - An exploration of the role of pharmacists within general practice clinics: the
      protocol for the pharmacists in practice study (PIPS).
AB  - BACKGROUND: Medication-related problems are a serious concern in Australian
      primary care. Pharmacist interventions have been shown to be effective in
      identifying and resolving these problems. Collaborative general practitioner
      pharmacist services currently available in Australia are limited and underused.
      Limitations include geographical isolation of pharmacists and lack of
      communication and access to patient information. Co-location of pharmacists
      within the general practice clinics is a possible solution. There have been no
      studies in the Australian setting exploring the role of pharmacists within
      general practice clinics.The aim of this study is to develop and test a
      multifaceted practice pharmacist role in primary care practices to improve the
      quality use of medicines by patients and clinic staff. METHODS/DESIGN: This is a
      multi-centre, prospective intervention study with a pre-post design and a
      qualitative component. A practice pharmacist will be located in each of two
      clinics and provide short and long patient consultations, drug information
      services and quality assurance activities. Patients receiving long consultation
      with a pharmacist will be followed up at 3 and 6 months. Based on sample size
      calculations, at least 50 patients will be recruited for long patient
      consultations across both sites. Outcome measures include the number, type and
      severity of medication-related problems identified and resolved; medication
      adherence; and patient satisfaction. Brief structured interviews will be
      conducted with patients participating in the study to evaluate their experiences
      with the service. Staff collaboration and satisfaction with the service will be
      assessed. DISCUSSION: This intervention has the potential to optimise medication
      use in primary care clinics leading to better health outcomes. This study will
      provide data about the effectiveness of the proposed model for pharmacist
      involvement in Australian general practice clinics, that will be useful to guide
      further research and development in this area. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry: ACTRN12612000742875.

PMID- 22876815
TI  - Fluorinated alcohols as promoters for the metal-free direct substitution reaction
      of allylic alcohols with nitrogenated, silylated, and carbon nucleophiles.
AB  - The direct allylic substitution reaction using allylic alcohols in 1,1,1,3,3,3
      hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) as reaction media
      is described. The developed procedure is simple, works under mild conditions (rt,
      50 and 70  degrees C), and proves to be very general, since different
      nitrogenated nucleophiles and carbon nucleophiles can be used achieving high
      yields, especially when HFIP is employed as solvent and aromatic allylic alcohols
      are the substrates. Thus, sulfonamides, carbamates, carboxamides, and amines can
      be successfully employed as nitrogen-based nucleophiles. Likewise, silylated
      nucleophiles such as trimethylsilylazide, allyltrimethylsilane, trimethylsilane,
      and trimethylsilylphenylacetylene give the corresponding allylic substitution
      products in high yields. Good results for the Friedel-Crafts adducts are also
      achieved with aromatic compounds (phenol, anisole, indole, and anilines) as
      nucleophiles. Particularly interesting are the results obtained with electron
      rich anilines, which can behave as nitrogenated or carbon nucleophiles depending
      on their electronic properties and the solvent employed. In addition, 1,3
      dicarbonyl compounds (acetylacetone and Meldrum's acid) are also successfully
      employed as soft carbon nucleophiles. Studies for mechanism elucidation are also
      reported, pointing toward the existence of carbocationic intermediates and two
      working reaction pathways for the obtention of the allylic substitution product.

PMID- 22876814
TI  - Different metastatic pattern according to the KRAS mutational status and site
      specific discordance of KRAS status in patients with colorectal cancer.
AB  - BACKGROUND: We evaluated the association between a KRAS mutational status and
      various clinicopathologic features including the metastatic pattern in patients
      with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of
      the KRAS status between primary tumor sites and paired metastatic organs were
      also analyzed. METHODS: The KRAS mutational status in codons 12, 13, and 61 from
      formalin-fixed sections of both primary tumors and related metastases was
      determined by sequencing analysis. One hundred forty-three Korean patients with
      MRCRC with available tissues (resection or biopsy) from both primary tumors and
      related metastatic sites were consecutively enrolled. RESULTS: The KRAS mutation
      rate was 52.4% (75/143) when considering both the primary and metastatic sites.
      When the relationship between the KRAS status and initial metastatic sites at the
      time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the
      initial metastatic site in patients with the KRAS mutation than in patients
      without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs.
      70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025)
      were less frequent as the initial metastatic organ in patients with the KRAS
      mutation than in patients without the KRAS mutation. The discordance rate of KRAS
      mutational status between primary and paired metastatic sites other than the lung
      was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate
      was significantly higher in matched lung metastases [32.4% (12/37)] than in other
      matched metastatic organs (P = 0.005). CONCLUSIONS: Organs initially involved by
      distant metastasis were different according to the KRAS mutational status in
      MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at
      metastatic sites other than the lung was generally high compared with primary
      tumor sites; however, lung metastasis had a high rate of KRAS discordance
      (32.4%).

PMID- 22876816
TI  - Detection of low-abundance protein phosphorylation by selective 18O labeling and
      mass spectrometry.
AB  - Reversible phosphorylation regulates the majority of intracellular networking and
      pathways. The study of this widely explored post-translational modification is
      usually challenged by low stoichiometric levels of modification. Many approaches
      have been developed to overcome this problem and to achieve rigorous
      characterization of protein phosphorylation. We describe a method for enhanced
      detection of low-abundance protein phosphorylation that uses selective
      introduction of (18)O label into phosphorylation sites with H(2)(18)O and mass
      spectrometric detection. The method was applied to introduce (18)O label into
      bacterially expressed Aurora A kinase phosphorylation sites and resulted in the
      representation of phosphorylated peptides as doublets or triplets according to
      the number of phosphate groups. A total of 28 phosphopeptides were observed by
      this method.

PMID- 22876817
TI  - New therapies in the treatment of melanoma.
AB  - INTRODUCTION: Therapies targeting immune checkpoints (CTLA-4) and the MAP kinase
      signaling pathway (RAS/RAF/MEK/ERK) have transformed the treatment of advanced
      melanoma in the past year. Agents aimed at other therapeutic targets of interest
      are being actively evaluated in the clinic. AREAS COVERED: Areas of active
      therapeutic interest in melanoma include immunotherapy, molecularly targeted
      therapy and chemotherapy; combinations of these modalities are now under
      systematic exploration. EXPERT OPINION: The evaluation of patients with melanoma
      now includes the molecular profiling of tumor mutations in the BRAF, as well as c
      Kit, NRAS and other genes that have been discovered to be drivers of different
      subsets of the disease. The analysis of the host immunological response to
      melanoma is equally important, as a basis for the development of immunotherapies
      that have been of value to melanoma patients in the adjuvant arena, as well as
      for therapy of metastatic disease. The understanding of these two facets of the
      disease will provide a more rational basis for the delivery of individualized
      therapy for the disease both in its advanced setting, and in the adjuvant arena,
      in the future.

PMID- 22876818
TI  - A three-stage discrete-time population model: continuous versus seasonal
      reproduction.
AB  - We consider a three-stage discrete-time population model with density-dependent
      survivorship and time-dependent reproduction. We provide stability analysis for
      two types of birth mechanisms: continuous and seasonal. We show that when birth
      is continuous there exists a unique globally stable interior equilibrium provided
      that the inherent net reproductive number is greater than unity. If it is less
      than unity, then extinction is the population's fate. We then analyze the case
      when birth is a function of period two and show that the unique two-cycle is
      globally attracting when the inherent net reproductive number is greater than
      unity, while if it is less than unity the population goes to extinction. The two
      birth types are then compared. It is shown that for low birth rates the adult
      average number over a one-year period is always higher when reproduction is
      continuous. Numerical simulations suggest that this remains true for high birth
      rates. Thus periodic birth rates of period two are deleterious for the three
      stage population model. This is different from the results obtained for a two
      stage model discussed by Ackleh and Jang (J. Diff. Equ. Appl., 13, 261-274,
      2007), where it was shown that for low birth rates seasonal breeding results in
      higher adult averages.

PMID- 22876819
TI  - A monotone approximation for a size-structured population model with a
      generalized environment.
AB  - We study a nonlinear size-structured population model with an environment general
      enough to include hierarchy. We also remove the standard requirement that
      individuals have nonnegative growth rates, which allows the modeling of
      populations in which individuals may experience a reduction in size. To show
      existence and uniqueness of the solution to the model, we establish a comparison
      principle and construct monotone sequences. A fully discretized numerical scheme
      based on these monotone sequences is presented and utilized to provide some
      numerical examples.

PMID- 22876820
TI  - Effect of pathogen-resistant vectors on the transmission dynamics of a vector
      borne disease.
AB  - A model is introduced for the transmission dynamics of a vector-borne disease
      with two vector strains, one wild and one pathogen-resistant; resistance comes at
      the cost of reduced reproductive fitness. The model, which assumes that vector
      reproduction can lead to the transmission or loss of resistance (reversion), is
      analyzed in a particular case with specified forms for the birth and force of
      infection functions. The vector component can have, in the absence of disease, a
      coexistence equilibrium where both strains survive. In the case where reversion
      is possible, this coexistence equilibrium is globally asymptotically stable when
      it exists. This equilibrium is still present in the full vector-host system,
      leading to a reduction of the associated reproduction number, thereby making
      elimination of the disease more feasible. When reversion is not possible, there
      can exist an additional equilibrium with only resistant vectors.

PMID- 22876821
TI  - Multiple mixed-type attractors in a competition model.
AB  - We show that a discrete-time, two-species competition model with Ricker
      (exponential) nonlinearities can exhibit multiple mixed-type attractors. By this
      is meant dynamic scenarios in which there are simultaneously present both
      coexistence attractors (in which both species are present) and exclusion
      attractors (in which one species is absent). Recent studies have investigated the
      inclusion of life-cycle stages in competition models as a casual mechanism for
      the existence of these kinds of multiple attractors. In this paper we investigate
      the role of nonlinearities in competition models without life-cycle stages.

PMID- 22876822
TI  - A sharp threshold for disease persistence in host metapopulations.
AB  - A sharp threshold is established that separates disease persistence from the
      extinction of small disease outbreaks in an S->E->I->R->S type metapopulation
      model. The travel rates between patches depend on disease prevalence. The
      threshold is formulated in terms of a basic replacement ratio (disease
      reproduction number), R(0), and, equivalently, in terms of the spectral bound of
      a transmission and travel matrix. Since frequency-dependent (standard) incidence
      is assumed, the threshold results do not require knowledge of a disease-free
      equilibrium. As a trade-off, for R(0)>1, only uniform weak disease persistence is
      shown in general, while uniform strong persistence is proved for the special case
      of constant recruitment of susceptibles into the patch populations. For R(0)<1,
      Lyapunov's direct stability method shows that small disease outbreaks do not
      spread much and eventually die out.

PMID- 22876823
TI  - Rabies in raccoons: optimal control for a discrete time model on a spatial grid.
AB  - An epidemic model for rabies in raccoons is formulated with discrete time and
      spatial features. The goal is to analyze the strategies for optimal distribution
      of vaccine baits to minimize the spread of the disease and the cost of
      implementing the control. Discrete optimal control techniques are used to derive
      the optimality system, which is then solved numerically to illustrate various
      scenarios.

PMID- 22876824
TI  - SIS epidemic attractors in periodic environments.
AB  - The demographic dynamics are known to drive the disease dynamics in constant
      environments. In periodic environments, we prove that the demographic dynamics do
      not always drive the disease dynamics. We exhibit a chaotic attractor in an SIS
      epidemic model, where the demograhic dynamics are asymptotically cyclic.
      Periodically forced SIS epidemic models are known to exhibit multiple attractors.
      We prove that the basins of attraction of these coexisting attractors have
      infinitely many components.

PMID- 22876825
TI  - Optimal control applied to native-invasive population dynamics.
AB  - This article presents a model for population interactions between an invasive and
      a native species, where the effect of disturbance in the system (such as
      flooding) is modeled as a control variable in the growth terms. The motivating
      example is cottonwood-salt cedar competition, with flooding being detrimental at
      low and high levels and being advantageous at medium levels, which led us to
      consider quadratic growth functions of the control. An objective functional is
      formulated to maximize the native species while minimizing the cost of
      implementing the control. A new existence result for an optimal control with
      these quadratic growth functions is given. Numerical results are examined for
      various parameter values. The results provide suggestions for managing the
      disturbance regime when invasive species are present.

PMID- 22876826
TI  - Numerical integration of population models satisfying conservation laws: NSFD
      methods.
AB  - Population models arising in ecology, epidemiology and mathematical biology may
      involve a conservation law, i.e. the total population is constant. In addition to
      these cases, other situations may occur for which the total population,
      asymptotically in time, approach a constant value. Since it is rarely the
      situation that the equations of motion can be analytically solved to obtain exact
      solutions, it follows that numerical techniques are needed to provide solutions.
      However, numerical procedures are only valid if they can reproduce fundamental
      properties of the differential equations modeling the phenomena of interest. We
      show that for population models, involving a dynamical conservation law the use
      of nonstandard finite difference (NSFD) methods allows the construction of
      discretization schemes such that they are dynamically consistent (DC) with the
      original differential equations. The paper will briefly discuss the NSFD
      methodology, the concept of DC, and illustrate their application to specific
      problems for population models.

PMID- 22876827
TI  - Dynamic reduction with applications to mathematical biology and other areas.
AB  - In a difference or differential equation one is usually interested in finding
      solutions having certain properties, either intrinsic properties (e.g. bounded,
      periodic, almost periodic) or extrinsic properties (e.g. stable, asymptotically
      stable, globally asymptotically stable). In certain instances it may happen that
      the dependence of these equations on the state variable is such that one may (1)
      alter that dependency by replacing part of the state variable by a function from
      a class having some of the above properties and (2) solve the 'reduced' equation
      for a solution having the remaining properties and lying in the same class. This
      then sets up a mapping Tau of the class into itself, thus reducing the original
      problem to one of finding a fixed point of the mapping. The procedure is applied
      to obtain a globally asymptotically stable periodic solution for a system of
      difference equations modeling the interaction of wild and genetically altered
      mosquitoes in an environment yielding periodic parameters. It is also shown that
      certain coupled periodic systems of difference equations may be completely
      decoupled so that the mapping Tau is established by solving a set of scalar
      equations. Periodic difference equations of extended Ricker type and also
      rational difference equations with a finite number of delays are also considered
      by reducing them to equations without delays but with a larger period. Conditions
      are given guaranteeing the existence and global asymptotic stability of periodic
      solutions.

PMID- 22876828
TI  - Lattice expansion in seamless bilayer graphene constrictions at high bias.
AB  - Our understanding of sp(2) carbon nanostructures is still emerging and is
      important for the development of high performance all carbon devices. For
      example, in terms of the structural behavior of graphene or bilayer graphene at
      high bias, little to nothing is known. To this end, we investigated bilayer
      graphene constrictions with closed edges (seamless) at high bias using in situ
      atomic resolution transmission electron microscopy. We directly observe a highly
      localized anomalously large lattice expansion inside the constriction. Both the
      current density and lattice expansion increase as the bilayer graphene
      constriction narrows. As the constriction width decreases below 10 nm, shortly
      before failure, the current density rises to 4 * 10(9) A cm(-2) and the
      constriction exhibits a lattice expansion with a uniaxial component showing an
      expansion approaching 5% and an isotropic component showing an expansion
      exceeding 1%. The origin of the lattice expansion is hard to fully ascribe to
      thermal expansion. Impact ionization is a process in which charge carriers
      transfer from bonding states to antibonding states, thus weakening bonds. The
      altered character of C-C bonds by impact ionization could explain the anomalously
      large lattice expansion we observe in seamless bilayer graphene constrictions.
      Moreover, impact ionization might also contribute to the observed anisotropy in
      the lattice expansion, although strain is probably the predominant factor.

PMID- 22876830
TI  - Binding of islet amyloid polypeptide to supported lipid bilayers and amyloid
      aggregation at the membranes.
AB  - Amyloid deposition of human islet amyloid polypeptide (hIAPP) in the islets of
      Langerhans is closely associated with the pathogenesis of type II diabetes
      mellitus. Despite substantial evidence linking amyloidogenic hIAPP to loss of
      beta-cell mass and decreased pancreatic function, the molecular mechanism of
      hIAPP cytotoxicity is poorly understood. We here investigated the binding of
      hIAPP and nonamyloidogenic rat IAPP to substrate-supported planar bilayers and
      examined the membrane-mediated amyloid aggregation. The membrane binding of IAPP
      in soluble and fibrillar states was characterized using quartz crystal
      microbalance with dissipation monitoring, revealing significant differences in
      the binding abilities among different species and conformational states of IAPP.
      Patterned model membranes composed of polymerized and fluid lipid bilayer domains
      were used to microscopically observe the amyloid aggregation of hIAPP in its
      membrane-bound state. The results have important implications for lipid-mediated
      aggregation following the penetration of hIAPP into fluid membranes. Using the
      fluorescence recovery after photobleaching method, we show that the processes of
      membrane binding and subsequent amyloid aggregation are accompanied by
      substantial changes in membrane fluidity and morphology. Additionally, we show
      that the fibrillar hIAPP has a potential ability to perturb the membrane
      structure in experiments of the fibril-mediated aggregation of lipid vesicles.
      The results obtained in this study using model membranes reveal that membrane
      bound hIAPP species display a pronounced membrane perturbation ability and
      suggest the potential involvement of the oligomeic forms of hAPP in membrane
      dysfunction.

PMID- 22876831
TI  - Unmediated by DNA electron transfer in redox-labeled DNA duplexes end-tethered to
      gold electrodes.
AB  - Electron transfer (ET) between gold electrodes and redox-labeled DNA duplexes,
      immobilized onto the electrodes through the alkanethiol linker at the 3'-end and
      having internal either methylene blue (MB) or anthraquinone (AQ) redox labels,
      was shown to depend on the redox label charge and the way the redox label is
      linked to DNA. For loosely packed DNA monolayers, the conjugation of the
      positively charged MB to DNA through the long and flexible alkane linker provided
      ET whose kinetics was formally governed by the diffusion of the redox label to
      the negatively charged electrode surface. For the uncharged AQ label no ET signal
      was detected. The conjugation of AQ to DNA through the short and more conductive
      acetylene linker did not provide the anticipated DNA-mediated ET to the AQ
      moiety: ET appeared to be low-efficient if any in the studied system, for which
      no intercalation of AQ within the DNA duplex occurred. The ET communication
      between the electrode and AQ, built in DNA through the acetylene linker, was
      achieved only when Ru(NH(3))(6)(3+) molecules were electrostatically attached to
      the DNA duplex, thus forming the electronic wire. These results are of particular
      importance both for the fundamental understanding of the interfacial behavior of
      the redox labeled DNA on electrodes and for the design of biosensors exploiting a
      variation of ET properties of DNA in the course of hybridization.

PMID- 22876832
TI  - I can play all night: examining the relationship between perceived tolerance and
      drinking game alcohol consumption.
AB  - The present study examined the impact of perceived tolerance to alcohol on
      maximum alcohol consumption while playing drinking games. Participants were
      student drinkers (N=3,546) from two west coast universities. Among these
      students, 69.2% (n=2,290) reported playing a drinking game in the past month.
      Analyses demonstrated game players had higher perceived tolerances, and consumed
      more alcohol than non-game players. A regression model revealed that higher
      levels of perceived tolerance were related to increased maximal alcohol
      consumption while playing drinking games. Study limitations and implications for
      future research are discussed.

PMID- 22876833
TI  - The failure of protein cancer biomarkers to reach the clinic: why, and what can
      be done to address the problem?
AB  - There is a plethora of published cancer biomarkers but the reality is that very
      few, if any, new circulating cancer biomarkers have entered the clinic in the
      last 30 years. I here try to explain this apparent oxymoron by classifying
      circulating cancer biomarkers into three categories: fraudulent reports (rare);
      true discoveries of biomarkers, that then fail to meet the demands of the clinic;
      and false discoveries, which represent artifactual biomarkers. I further provide
      examples of combinations of some known cancer biomarkers that can perform well in
      niche clinical applications, despite individually being not useful.

PMID- 22876834
TI  - GSA-PCA: gene set generation by principal component analysis of the Laplacian
      matrix of a metabolic network.
AB  - BACKGROUND: Gene Set Analysis (GSA) has proven to be a useful approach to
      microarray analysis. However, most of the method development for GSA has focused
      on the statistical tests to be used rather than on the generation of sets that
      will be tested. Existing methods of set generation are often overly simplistic.
      The creation of sets from individual pathways (in isolation) is a poor reflection
      of the complexity of the underlying metabolic network. We have developed a novel
      approach to set generation via the use of Principal Component Analysis of the
      Laplacian matrix of a metabolic network. We have analysed a relatively simple
      data set to show the difference in results between our method and the current
      state-of-the-art pathway-based sets. RESULTS: The sets generated with this method
      are semi-exhaustive and capture much of the topological complexity of the
      metabolic network. The semi-exhaustive nature of this method has also allowed us
      to design a hypergeometric enrichment test to determine which genes are likely
      responsible for set significance. We show that our method finds significant
      aspects of biology that would be missed (i.e. false negatives) and addresses the
      false positive rates found with the use of simple pathway-based sets.
      CONCLUSIONS: The set generation step for GSA is often neglected but is a crucial
      part of the analysis as it defines the full context for the analysis. As such,
      set generation methods should be robust and yield as complete a representation of
      the extant biological knowledge as possible. The method reported here achieves
      this goal and is demonstrably superior to previous set analysis methods.

PMID- 22876835
TI  - Transdermal buprenorphine for postoperative pain control in gynecological
      surgery: a prospective randomized study.
AB  - OBJECTIVE: Although numerous methods are available for postoperative pain (POP)
      management, new approaches are constantly being investigated. This feasibility
      study assessed the buprenorphine transdermal therapeutic system (Bup-TTS) for the
      treatment of POP after gynecological open surgery. RESEARCH DESIGN AND METHODS:
      Forty-five patients were prospectively randomized to different Bup-TTS dosages
      (17.5, 35, or 52.5 MUg/h). Patients were blinded with regard to patch dose. MAIN
      OUTCOME MEASURES: Efficacy was evaluated in terms of rescue boluses (intravenous
      morphine 2 mg in the first six postoperative hours, intravenous ketorolac 30 mg
      thereafter) required to achieve a static and dynamic Numerical Rating Scale (sNRS
      and dNRS) score <=4. Side effects were evaluated from patch application (12 hours
      before surgery) until the 72nd postoperative hour. Patient satisfaction regarding
      POP management was assessed via anonymous questionnaire. RESULTS: All Bup-TTS
      groups required additional postoperative analgesia, particularly in the first
      postoperative hour. No between-group differences in sNRS/dNRS values were
      recorded at emergence from anesthesia. A significant inverse correlation occurred
      between Bup-TTS dosage and use of morphine (p = 0.04), ketorolac (p = 0.04) or
      both rescues (p = 0.02). Postoperative nausea/vomiting occurred in 3.1% of
      assessments, with no between-group differences and a significant correlation with
      morphine amount (p = 0.01). No serious side effects occurred. Despite no between
      group difference, patient satisfaction was inversely correlated with the number
      of rescue doses (p < 0.001). Study limitations include the small sample size, the
      absence of a control group treated with a more conventional technique for POP
      relief, the focus on selected patients at low perioperative risk and the presence
      of slightly different types of open surgery (hysterectomy vs myomectomy only).
      CONCLUSION: Bup-TTS efficacy was directly proportional to its dosage, although
      additional analgesia was required, particularly in the first postoperative hour.
      Moreover, the consumption of morphine and ketorolac was inversely correlated to
      the Bup-TTS dosage. Increasing Bup-TTS doses were not associated with an
      increased incidence of side effects. Bup-TTS appears a safe and feasible approach
      for moderate POP management; further larger studies are warranted.

PMID- 22876836
TI  - Neurology: Letter to the editor. Re: Sun P, Kohrman M, Liu J et al. Outcomes of
      resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA
      related tuberous sclerosis complex: a national claims database analysis. Curr Med
      Res Opin 2012;28:657-63.

PMID- 22876837
TI  - 2011 Annual Report of the American Psychological Association.

PMID- 22876838
TI  - Genetic and bioinformatic analyses of the expression and function of PI3K
      regulatory subunit PIK3R3 in an Asian patient gastric cancer library.
AB  - BACKGROUND: While there is strong evidence for phosphatidylinositol 3-kinase
      (PI3K) involvement in cancer development, there is limited information about the
      role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K
      regulatory subunit p55gamma, is over-expressed in glioblastoma and ovarian
      cancers, but its expression in gastric cancer (GC) is not known. We thus used
      genetic and bioinformatic approaches to examine PIK3R3 expression and function in
      GC, the second leading cause of cancer mortality world-wide and highly prevalent
      among Asians. METHODS: Primary GC and matched non-neoplastic mucosa tissue
      specimens from a unique Asian patient gastric cancer library were comprehensively
      profiled with platforms that measured genome-wide mRNA expression, DNA copy
      number variation, and DNA methylation status. Function of PIK3R3 was predicted by
      IPA pathway analysis of co-regulated genes with PIK3R3, and further investigated
      by siRNA knockdown studies. Cell proliferation was estimated by crystal violet
      dye elution and BrdU incorporation assay. Cell cycle distribution was analysed by
      FACS. RESULTS: PIK3R3 was significantly up-regulated in GC specimens (n = 126, p
      < 0.05), and 9.5 to 15% tumors showed more than 2 fold increase compare to the
      paired mucosa tissues. IPA pathway analysis showed that PIK3R3 promoted cellular
      growth and proliferation. Knockdown of PIK3R3 decreased the growth of GC cells,
      induced G0/G1 cell cycle arrest, decreased retinoblastoma protein (Rb)
      phosphorylation, cyclin D1, and PCNA expression. CONCLUSION: Using a combination
      of genetic, bioinformatic, and molecular biological approaches, we showed that
      PIK3R3 was up-regulated in GC and promoted cell cycle progression and
      proliferation; and thus may be a potential new therapeutic target for GC.

PMID- 22876839
TI  - The association between nurse staffing and hospital outcomes in injured patients.
AB  - BACKGROUND: The enormous fiscal pressures facing trauma centers may lead trauma
      centers to reduce nurse staffing and to make increased use of less expensive and
      less skilled personnel. The impact of nurse staffing and skill mix on trauma
      outcomes has not been previously reported. The goal of this study was to examine
      whether nurse staffing levels and nursing skill mix are associated with trauma
      patient outcomes. METHODS: We used data from the Healthcare Cost and Utilization
      Project Nationwide Inpatient Sample to perform a cross-sectional study of 70,142
      patients admitted to 77 Level I and Level II centers. Logistic regression models
      were used to examine the association between nurse staffing measures and (1)
      mortality, (2) healthcare associated infections (HAI), and (3) failure-to-rescue.
      We controlled for patient risk factors (age, gender, injury severity, mechanism
      of injury, comorbidities) and hospital structural characteristics (trauma center
      status - Level I versus Level II, hospital size, ownership, teaching status,
      technology level, and geographic region). RESULTS: A 1% increase in the ratio of
      licensed practical nurse (LPN) to total nursing time was associated with a 4%
      increase in the odds of mortality (adj OR 1.04; 95% CI: 1.02-1.06; p = 0.001) and
      a 6% increase in the odds of sepsis (adj OR 1.06: 1.03-1.10; p < 0.001).
      Hospitals in the highest quartile of LPN staffing had 3 excess deaths (95% CI:
      1.2, 5.1) and 5 more episodes of sepsis (95% CI: 2.3, 7.6) per 1000 patients
      compared to hospitals in the lower quartile of LPN staffing. CONCLUSIONS: Higher
      hospital LPN staffing levels are independently associated with slightly higher
      rates of mortality and sepsis in trauma patients admitted to Level I or Level II
      trauma centers.

PMID- 22876841
TI  - How flocculation can explain coexistence in the chemostat.
AB  - We study a chemostat model in which two microbial species grow on a single
      resource. We show that species coexistence is possible when the species which
      would normally win the exclusive competition aggregates in flocs. Our
      mathematical analysis exploits the fact that flocculation is fast compared to
      biological growth, a common hypothesis in floc models. A numerical study shows
      the validity of this approach in a large parameter range. We indicate how our
      model yields a mechanistic justification for the so-called density-dependent
      growth.

PMID- 22876840
TI  - MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion
      through targeting HOXA5.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play
      important roles in the pathogenesis of human diseases by negatively regulating
      gene expression. Although miR-196a has been implicated in several other cancers,
      its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present
      study was to examine the expression pattern of miR-196a in NSCLC and its clinical
      significance, as well as its biological role in tumor progression. METHODS:
      Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines
      by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The
      effect of DNA methylation on miR-196a expression was investigated by 5-aza-2
      deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on
      proliferation was evaluated by MTT and colony formation assays, and cell
      migration and invasion were evaluated by transwell assays. Analysis of target
      protein expression was determined by western blotting. Luciferase reporter
      plasmids were constructed to confirm the action of miR-196a on downstream target
      genes, including HOXA5. Differences between the results were tested for
      significance using Student's t-test (two-tailed). RESULTS: miR-196a was highly
      expressed both in NSCLC samples and cell lines compared with their corresponding
      normal counterparts, and the expression of miR-196a may be affected by DNA
      demethylation. Higher expression of miR-196a in NSCLC tissues was associated with
      a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In
      vitro functional assays demonstrated that modulation of miR-196a expression
      affected NSCLC cell proliferation, migration and invasion. Our analysis showed
      that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein
      levels, and luciferase assays confirmed that miR-196a directly bound to the
      3'untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using
      RNAi was shown to promote NSCLC cell proliferation, migration and invasion.
      Finally, we observed an inverse correlation between HOXA5 and miR-196a expression
      in NSCLC tissues. CONCLUSIONS: Our findings indicate that miR-196a is
      significantly up-regulated in NSCLC tissues, and regulates NSCLC cell
      proliferation, migration and invasion, partially via the down-regulation of
      HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC
      intervention.

PMID- 22876842
TI  - Plankton-toxin interaction with a variable input nutrient.
AB  - A simple model of phytoplankton-zooplankton interaction with a periodic input
      nutrient is presented. The model is then used to study a nutrient-plankton
      interaction with a toxic substance that inhibits the growth rate of plankton
      populations. The effects of the toxin upon the existence, magnitude, and
      stability of the periodic solutions are discussed. Numerical simulations are also
      provided to illustrate analytical results and to compare more complicated
      dynamical behaviour.

PMID- 22876843
TI  - Spatial synchrony through density-independent versus density-dependent dispersal.
AB  - Many theoretical studies support the notion that strong dispersal fosters spatial
      synchrony. Nonetheless, the effect of conditional vs. unconditional dispersal has
      remained a matter of controversy. We scrutinize recent findings on a
      desynchronizing effect of negative density-dependent dispersal based on spatially
      explicit simulation models. Keeping net emigration rates equivalent, we compared
      density-independent and density-dependent dispersal for different types of
      intraspecific density regulation, ranging from under-compensation to over
      compensation. In general, density-independent dispersal possessed a slightly
      higher synchronizing potential but this effect was very small and sensitive
      compared to the influence of the type of local density regulation. Notably,
      consistent outcomes for the comparison of conditional dispersal strategies
      strongly relied on the control of equivalent emigration rates. We conclude that
      the strength of dispersal is more important for spatial synchrony than its
      density dependence. Most important is the mode of intraspecific density
      regulation.

PMID- 22876844
TI  - Predation may defeat spatial spread of infection.
AB  - A model of a phytoplankton-zooplankton prey-predator system with viral infection
      of phytoplankton is investigated. Virus particles (V) are taken into account by
      an explicit equation. Phytoplankton is split into a susceptible (S) and an
      infected (I) class. A lytic infection is considered, thus, infected phytoplankton
      cells stop reproducing as soon as the infection starts and die at an increased
      mortality rate. Zooplankton (Z) is grazing on both susceptible and infected
      phytoplankton following a Holling-type II functional response. After the local
      dynamics of the V-S-I-Z system is analysed, numerical solutions of a stochastic
      reaction-diffusion model of the four species are presented. These show a spatial
      competition between zooplankton and viruses, although these two species are not
      explicitly coupled by the model equations.

PMID- 22876845
TI  - The importance of census times in discrete-time growth-dispersal models.
AB  - Dispersal has been the focus of spatial ecology for a few decades. What should be
      a proper theoretical framework for understanding and modelling of dispersal
      processes remains a controversial issue though. Integrodifference equations (IDE)
      model the spatial dynamics of a population with distinct growth and dispersal
      stages in their life cycle. Depending on the stage observed, the equations take
      on different forms, only one of which is usually studied in the literature. Here
      we reveal that while these different forms are mathematically equivalent, the
      biological conclusions drawn from the different forms may differ considerably. We
      provide a summary of similarities and differences and point out the greatest
      potential caveats when applying IDE.

PMID- 22876846
TI  - An impulsive delayed SEIRS epidemic model with saturation incidence.
AB  - A delayed SEIRS epidemic model with pulse vaccination and saturation incidence
      rate is investigated. Using Krasnoselskii's fixed-point theorem, we obtain the
      existence of infection-free periodic solution of the impulsive delayed epidemic
      system. We define some new threshold values R(1), R(2) and R(3). Further, using
      the comparison theorem, we obtain the explicit formulae of R(1) and R(2). Under
      the condition R(1) < 1, the infection-free periodic solution is globally
      attractive, and that R(2) > 1 implies that the disease is permanent. Theoretical
      results show that the disease will be extinct if the vaccination rate is larger
      than theta* and the disease is uniformly persistent if the vaccination rate is
      less than theta(*). Our results indicate that a long latent period of the disease
      or a large pulse vaccination rate will lead to eradication of the disease.
      Moreover, we prove that the disease will be permanent as R(3) > 1.

PMID- 22876848
TI  - Hydrogen bonding in pyridine N-oxide/acid systems: proton transfer and fine
      details revealed by FTIR, NMR, and X-ray diffraction.
AB  - The H-bonded complexes of pyridine N-oxide (PyO) with H(2)O, acetic, cyanoacetic,
      propiolic, tribromoacetic, trichloroacetic, trifluoroacetic, hydrochloric, and
      methanesulfonic acids have been studied by FTIR and NMR spectroscopy, X-ray
      diffraction, and quantum chemical DFT calculations. Correlations between
      vibrational frequencies of the NO stretching and PyO ring modes and geometric
      parameters of the H-bond have been established. FTIR experiments show and DFT
      calculations confirm that definite discontinuity is present in the vicinity of
      the midpoint in the proton transfer pathway. The established correlations
      significantly aid in the understanding of fine effects such as the isotope
      (deuteration) effect, crystal-to-solution transition, or criticality of aqueous
      solutions induced by ionic pairs. Geometric isotope effect in the ionic H-bond
      aggregate of PyO.H(D)Cl was found to be extraordinary large. Measured FTIR,
      CP/MAS, and high-resolution (13)C NMR spectra indicate that H-bond in the PyO.HCl
      complex in polar solvent can potentially be more ionic than in the crystal.
      Vibrational modes of ionic pairs originating via proton transfer in H-bond
      complexes can provide new information concerning the interionic interaction and
      its role in the phase separation and mezo-structuring processes. The results are
      compared to the relevant data for PyO.HCl complex in argon matrix.

PMID- 22876849
TI  - Low 25OH vitamin D2 levels found in untreated Alzheimer's patients, compared to
      acetylcholinesterase-inhibitor treated and controls.
AB  - Following contradictory reports, the aim of this study was to apply our highly
      specific novel assay to delineate the relationship between vitamin D forms and
      Alzheimer's disease. The study incorporated patients, both untreated and treated
      with acetylcholinesterase inhibitors, along with controls. Patients were grouped
      as A: untreated (n=26) and B: treated with donepezil, rivastigmine or galantamine
      (n=44). The study included a control Group (C, n=35) with no cognitive
      impairment. Cognitive function was assessed using the MMSE. Levels of vitamin D
      forms were measured using liquid chromatography-mass spectrometry (LC-MS/MS) and
      calcium measurements were conducted using inductively coupled plasma-mass
      spectrometry (ICP-MS). In the cohort studied, no relationship was observed
      between MMSE score, calcium and any form of vitamin D. The indisputable finding
      is that the level of 25hydroxyvitamin D2 (25OHD2) (3.165 +/- 6.352 nmol/L, p <
      0.001) was significantly lower in the untreated Group (A) compared to the control
      and treated groups (7.932 +/- 9.196 and 12.138 +/- 15.682 nmol/L, respectively).
      In contrast, the levels of the primary forms, vitamin D2 and total vitamin D were
      the highest for the untreated group. Vitamin D levels, assessed as 25OHD are
      significantly lower in patients suffering from Alzheimer's disease arising from
      extremely low levels of 25OHD2 along with low levels of 25OHD3. Treatment with
      acetylcholinesterase inhibitors reverses this deficit. Further research is
      warranted to delineate the mode of action of acetylcholinesterase inhibitors with
      respect to normalising 25OHD2 levels. These observations resulted in the
      hypothesis that along with the common functions of vitamin D, different forms
      have distinct roles in health and disease.

PMID- 22876850
TI  - Nanoscale strainability of graphene by laser shock-induced three-dimensional
      shaping.
AB  - Graphene has many promising physical properties. It has been discovered that
      local strain in a graphene sheet can alter its conducting properties and
      transport gaps. It is of great importance to develop scalable strain engineering
      techniques to control the local strains in graphene and understand the limit of
      the strains. Here, we present a scalable manufacturing process to generate three
      dimensional (3D) nanostructures and thus induce local strains in the graphene
      sheet. This process utilizes laser-induced shock pressure to generate 3D tunable
      straining in the graphene sheet. The size dependent straining limit of the
      graphene and the critical breaking pressure are both studied. It is found that
      the graphene film can be formed to a circular mold (~50 nm in diameter) with an
      aspect ratio of 0.25 and strain of 12%, and the critical breaking pressure is
      1.77 GPa. These values were found to be decreasing with the increase of mold
      size. The local straining and breaking of graphene film are verified by Raman
      spectra. Large scale processing of the graphene sheet into nanoscale patterns is
      presented. The process could be scaled up to roll-to-roll process by changing
      laser beam size and scanning speed. The presented laser shock straining approach
      is a fast, tunable, and low-cost technique to realize strain engineering of
      graphene for its applications in nanoelectrical devices.

PMID- 22876851
TI  - Evidence of nonelectrochemical shift reaction on a CO-tolerant high-entropy state
      Pt-Ru anode catalyst for reliable and efficient residential fuel cell systems.
AB  - A randomly mixed monodispersed nanosized Pt-Ru catalyst, an ultimate catalyst for
      CO oxidation reaction, was prepared by the rapid quenching method. The mechanism
      of CO oxidation reaction on the Pt-Ru anode catalyst was elucidated by
      investigating the relation between the rate of CO oxidation reaction and the
      current density. The rate of CO oxidation reaction increased with an increase in
      unoccupied sites kinetically formed by hydrogen oxidation reaction, and the rate
      was independent of anode potential. Results of extended X-ray absorption fine
      structure spectroscopy showed the combination of N(Pt-Ru)/(N(Pt-Ru) + N(Pt-Pt)) ?
      M(Ru)/(M(Pt) + M(Ru)) and N(Ru-Pt)/(N(Ru-Pt) + N(Ru-Ru)) ? M(Pt)/(M(Ru) + M(Pt)),
      where N(Pt-Ru)(N(Ru-Pt)), N(Pt-Pt)(N(Ru-Ru)), M(Pt), and M(Ru) are the
      coordination numbers from Pt(Ru) to Ru(Pt) and Pt (Ru) to Pt (Ru) and the molar
      ratios of Pt and Ru, respectively. This indicates that Pt and Ru were mixed with
      a completely random distribution. A high-entropy state of dispersion of Pt and Ru
      could be maintained by rapid quenching from a high temperature. It is concluded
      that a nonelectrochemical shift reaction on a randomly mixed Pt-Ru catalyst is
      important to enhance the efficiency of residential fuel cell systems under
      operation conditions.

PMID- 22876853
TI  - Conjugate addition vs Heck reaction: a theoretical study on competitive coupling
      catalyzed by isoelectronic metal (Pd(II) and Rh(I)).
AB  - Density functional theory studies have been carried out to investigate the
      mechanism of the Pd(II)(bpy)- and Rh(I)(bpy)-catalyzed conjugate additions and
      their competitive Heck reactions involving alpha,beta-unsaturated carbonyl
      compounds. The critical steps of the mechanism are insertion and termination. The
      insertion step favors 1,2-addition of the vinyl-coordinated species to generate a
      stable C-bound enolate intermediate, which then may isomerize to either an oxa-pi
      allyl species or an O-bound enolate. The termination step involves a competition
      between beta-hydride elimination, leading to a Heck reaction product, and
      protonolysis reaction that gives a conjugate addition product. These two pathways
      are competitive in the Pd(II)-catalyzed reaction, while a preference for
      protonolysis has been found in the Rh(I)-catalyzed reaction. The calculations are
      in good agreement with the experimental observations. The potential energy
      surface and the rate-determining step of the beta-hydride elimination are similar
      for both Pd(II)- and Rh(I)-catalyzed processes. The rate-determining steps of the
      Pd(II)- and Rh(I)-catalyzed protonolysis are different. Introduction of an N- or
      P-ligand significantly stabilizes the protonolysis transition state via the O
      bound enolate or oxa-pi-allyl complex intermediate, resulting in a reduced free
      energy of activation. However, the barrier of the beta-hydride elimination is
      less sensitive to ligands. For the Rh(I)-catalyzed reaction, protonolysis is
      calculated to be more favorable than the beta-hydride elimination for all
      investigated N and P ligands due to the significant ligand stabilization to the
      protonolysis transition state. For the Pd(II)-catalyzed reaction, the complex
      with monodentate pyridine ligands prefers the Heck-type product through beta
      hydride elimination, while the complex with bidentate N and P ligands favors the
      protonolysis. The theoretical finding suggests the possibility to control the
      selectivity between the conjugate addition and the Heck reaction by using proper
      ligands.

PMID- 22876854
TI  - The role of heat shock protein 90 in modulating ischemia-reperfusion injury in
      the kidney.
AB  - INTRODUCTION: Kidney transplantation is the gold standard treatment for end-stage
      renal disease. Ischemia-reperfusion injury (IRI) is an unavoidable consequence of
      the transplantation procedure and is responsible for delayed graft function and
      poorer long-term outcomes. AREAS COVERED: Pharmacological induction of heat shock
      protein (Hsp) expression is an emerging pre-conditioning strategy aimed at
      reducing IRI following renal transplantation. Hsp90 inhibition up-regulates
      protective Hsps (especially Hsp70) and potentially down-regulates NF-kappaB by
      disruption of the IkappaB kinase (IKK) complex. However, the clinical application
      of Hsp90 inhibitors is currently limited by their toxicity profile and the exact
      mechanism of protection conferred is unknown. Toll-like receptor 4 (TLR4) is a
      further regulator of NF-kappaB and recent studies suggest TLR4 plays a dominant
      role in mediating kidney damage following IRI. The full interaction of Hsps with
      TLRs is yet to be delineated and whether TLR4 signalling can be targeted by Hsp90
      inhibition in IRI remains uncertain. EXPERT OPINION: Pharmacological pre
      conditioning by Hsp90 inhibition involves direct treatment to the kidney donor
      and/or organ, which aims to reduce injury prior to the onset of ischemia. The
      major challenges going forward are to establish the exact mechanism of protection
      offered by these drugs and the investgiation of less toxic analogues that could
      be safely translated into human studies.

PMID- 22876855
TI  - Facing a new frontier: safety in cyberspace and challenges for nursing.

PMID- 22876852
TI  - Comparative host protein interactions with HTLV-1 p30 and HTLV-2 p28: insights
      into difference in pathobiology of human retroviruses.
AB  - BACKGROUND: Human T lymphotropic virus type-1 (HTLV-1) and type 2 (HTLV-2) are
      closely related human retroviruses, but have unique disease associations. HTLV-1
      is the causative agent of an aggressive T-cell leukemia known as adult T-cell
      leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), and other inflammatory diseases. HTLV-2 infection has not been clearly
      associated with any disease condition. Although both viruses can transform T
      cells in vitro, the HTLV-1 provirus is mainly detected in CD4+ T cells whereas
      HTLV-2 is mainly detected in CD8+ T cells of infected individuals. HTLV-1 and
      HTLV-2 encode accessory proteins p30 and p28, respectively, which share partial
      amino acid homology and are required for viral persistence in vivo. The goal of
      this study was to identify host proteins interacting with p30 and p28 in order to
      understand their role in pathogenesis. RESULTS: Affinity-tag purification coupled
      with mass spectrometric (MS) analyses revealed 42 and 22 potential interacting
      cellular partners of p30 and p28, respectively. Of these, only three cellular
      proteins, protein arginine methyltransferase 5 (PRMT5), hnRNP K and 60 S
      ribosomal protein L8 were detected in both p30 and p28 fractions. To validate the
      proteomic results, four interacting proteins were selected for further analyses
      using immunoblot assays. In full agreement with the MS analysis two cellular
      proteins REGgamma and NEAF-interacting protein 30 (NIP30) selectively interacted
      with p30 and not with p28; heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1)
      bound to p28 and not to p30; and PRMT5 interacted with both p30 and p28. Further
      studies demonstrated that reduced levels of PRMT5 resulted in decreased HTLV-2
      viral gene expression whereas the viral gene expression of HTLV-1 was unchanged.
      CONCLUSION: The comparisons of p30 and p28 host protein interaction proteome
      showed striking differences with some degree of overlap. PRMT5, one of the host
      proteins that interacted with both p30 and p28 differentially affected HTLV-1 and
      HTLV-2 viral gene expression suggesting that PRMT5 is involved at different
      stages of HTLV-1 and HTLV-2 biology. These findings suggest that distinct host
      protein interaction profiles of p30 and p28 could, in part, be responsible for
      differences in HTLV-1 and HTLV-2 pathobiology. This study provides new avenues of
      investigation into mechanisms of viral infection, tropism and persistence.

PMID- 22876860
TI  - Structure of a specialized acyl carrier protein essential for lipid A
      biosynthesis with very long-chain fatty acids in open and closed conformations.
AB  - The solution nuclear magnetic resonance (NMR) structures and backbone (15)N
      dynamics of the specialized acyl carrier protein (ACP), RpAcpXL, from
      Rhodopseudomonas palustris, in both the apo form and holo form modified by
      covalent attachment of 4'-phosphopantetheine at S37, are virtually identical,
      monomeric, and correspond to the closed conformation. The structures have an
      extra alpha-helix compared to the archetypical ACP from Escherichia coli, which
      has four helices, resulting in a larger opening to the hydrophobic cavity.
      Chemical shift differences between apo- and holo-RpAcpXL indicated some
      differences in the hinge region between alpha2 and alpha3 and in the hydrophobic
      cavity environment, but corresponding changes in nuclear Overhauser effect cross
      peak patterns were not detected. In contrast to the NMR structures, apo-RpAcpXL
      was observed in an open conformation in crystals that diffracted to 2.0 A
      resolution, which resulted from movement of alpha3. On the basis of the crystal
      structure, the predicted biological assembly is a homodimer. Although the
      possible biological significance of dimerization is unknown, there is potential
      that the resulting large shared hydrophobic cavity could accommodate the very
      long-chain fatty acid (28-30 carbons) that this specialized ACP is known to
      synthesize and transfer to lipid A. These structures are the first
      representatives of the AcpXL family and the first to indicate that dimerization
      may be important for the function of these specialized ACPs.

PMID- 22876861
TI  - Development of an in vitro drug screening assay using Schistosoma haematobium
      schistosomula.
AB  - BACKGROUND: The development of novel antischistosomal drugs is crucial, as
      currently no vaccine and only a single drug is available for the treatment of
      schistosomiasis. Fast and accurate in vitro assays are urgently needed to
      identify new drug candidates and research efforts should include Schistosoma
      haematobium. The aim of the present study was to develop a S. haematobium drug
      sensitivity assay based on newly transformed schistosomula (NTS). METHODS: We
      first undertook comparative studies on the cercarial emergence rhythms of the
      intermediate host snails Biomphalaria glabrata (S. mansoni) and Bulinus truncatus
      (S. haematobium). Two transformation methods as well as three purification
      methods were studied on S. haematobium cercariae in order to produce a large
      number of viable and clean NTS. Known antischistosomal drugs were tested in the
      established NTS assay in vitro. Drug effects were evaluated either
      microscopically or fluorometrically, using a resazurin based viability marker.
      Microscopically obtained IC50 values were compared with results obtained for S.
      mansoni. RESULTS: A circadian rhythm existed in both snail species. Infected B.
      truncatus snails shed less cercariae than B. glabrata during the testing period.
      The highest transformation rate (69%) of S. haematobium cercariae into NTS was
      obtained with the vortex transformation (mechanical input) and the highest
      purification factor was observed using Percoll(r). The fluorimetric readout based
      on resazurin was very precise in detecting dead or/and severely damaged
      schistosomula. CONCLUSIONS: With the use of viability markers such as resazurin,
      drug screening assays using S. haematobium NTS can be efficiently performed.
      However, drugs acting on the morphology and motility of S. haematobium NTS, such
      as metrifonate are missed. Drug sensitivity assays with NTS of both species, S.
      haematobium and S. mansoni, showed very similar results using known
      antischistosomal drugs. The S. mansoni NTS assay might be more suitable as
      primary screen in drug discovery efforts, which ultimately aim for a broad
      spectrum antischistosomal drug as a larger number of S. mansoni NTS can be
      generated.

PMID- 22876863
TI  - Unusual occurrence of amyotrophic lateral sclerosis in myasthenia gravis.

PMID- 22876862
TI  - Biomarkers of oxidative stress in fetal and neonatal diseases.
AB  - Oxidative stress (OS) is strongly involved in the pathogenesis of many fetal and
      newborn diseases. A low efficient antioxidant systems in preterm babies are not
      able to counteract the harmful effects of free radicals (FRs), leading to "FRs
      related disease" of newborns promoting cellular, tissue and organ damages. The
      dangerous effects of FRs are linked to their property of being very unstable
      molecules and their ability to react with lipids, proteins, polysaccharides,
      nucleic acids, causing functional alterations within the cell, until cell death.
      OS is difficult to be measured in vivo, because FRs have a very short half-life.
      Actually, measurements of lipid peroxidation reach high specificity and
      sensitivity with the discovery of stable compounds, isoprostanes. Recent studies
      evaluating the damaging effects of FRs in the perinatal period, have observed a
      direct relation between the degree of OS and the severity of oxidative damage in
      the course of pregnancy and in perinatal period, with an interesting predictive
      role of OS biomarkers for diseases resulting from oxidative injury. The
      validation of a biomarker profile for early identification of newborns at high
      risk of OS, will pave the way to new clinical preventative or therapeutic
      approaches to reduce the prevalence of neonatal disability.

PMID- 22876864
TI  - Sequencing the genome of Marssonina brunnea reveals fungus-poplar co-evolution.
AB  - BACKGROUND: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf
      spot that devastates poplar plantations by defoliating susceptible trees before
      normal fall leaf drop. RESULTS: We sequence the genome of M. brunnea with a size
      of 52 Mb assembled into 89 scaffolds, representing the first sequenced
      Dermateaceae genome. By inoculating this fungus onto a poplar hybrid clone, we
      investigate how M. brunnea interacts and co-evolves with its host to colonize
      poplar leaves. While a handful of virulence genes in M. brunnea, mostly from the
      LysM family, are detected to up-regulate during infection, the poplar down
      regulates its resistance genes, such as nucleotide binding site domains and
      leucine rich repeats, in response to infection. From 10,027 predicted proteins of
      M. brunnea in a comparison with those from poplar, we identify four poplar
      transferases that stimulate the host to resist M. brunnea. These transferas
      encoding genes may have driven the co-evolution of M. brunnea and Populus during
      the process of infection and anti-infection. CONCLUSIONS: Our results from the
      draft sequence of the M. brunnea genome provide evidence for genome-genome
      interactions that play an important role in poplar-pathogen co-evolution. This
      knowledge could help to design effective strategies for controlling Marssonina
      leaf spot in poplar.

PMID- 22876865
TI  - The D/I polymorphism in the angiotensin-converting enzyme gene and chronic
      obstructive pulmonary disease risk: a meta-analysis.
AB  - BACKGROUND: The deletion/insertion (D/I) polymorphism in the angiotensin
      converting enzyme (ACE) gene has been implicated in susceptibility of chronic
      obstruction pulmonary disease (COPD), but a number of studies have reported
      inconclusive results. The aim of this study is to investigate the relationship
      between the D/I polymorphism in the ACE gene and COPD risk by meta-analysis.
      METHOD: We searched Pubmed database, Embase database, CNKI database and Wanfang
      database, covering all studies until October 10, 2011. Statistical analysis was
      performed by using the software Revman4.2 and STATA 10.0. RESULTS: A total of 710
      COPD cases and 862 controls in 10 case-control studies were included in this
      study. The results suggested that the DD homozygote carriers did not have an
      increased or decreased risk of COPD when compared with the heterozygote DI and II
      homozygote carriers. However, in the subgroup analysis by race, significant
      increased risks were found in Asian DD homozygote carriers (OR = 2.6 and 95% CI =
      1.47-4.57 for DD vs. DI+II) but not in Caucasian DD homozygote carriers (OR =
      0.91, 95%CI = 0.69-1.22, P = 0.54 for DD vs. DI+II). CONCLUSIONS: This meta
      analysis suggested that the ACE gene is a COPD susceptible gene in Asian
      populations. Future studies are needed to validate our conclusions..

PMID- 22876866
TI  - Atomistic boron-doped graphene field-effect transistors: a route toward unipolar
      characteristics.
AB  - We report fully quantum simulations of realistic models of boron-doped graphene
      based field-effect transistors, including atomistic details based on DFT
      calculations. We show that the self-consistent solution of the three-dimensional
      (3D) Poisson and Schrodinger equations with a representation in terms of a tight
      binding Hamiltonian manages to accurately reproduce the DFT results for an
      isolated boron-doped graphene nanoribbon. Using a 3D Poisson/Schrodinger solver
      within the non-equilibrium Green's function (NEGF) formalism, self-consistent
      calculations of the gate-screened scattering potentials induced by the boron
      impurities have been performed, allowing the theoretical exploration of the
      tunability of transistor characteristics. The boron-doped graphene transistors
      are found to approach unipolar behavior as the boron concentration is increased
      and, by tuning the density of chemical dopants, the electron-hole transport
      asymmetry can be finely adjusted. Correspondingly, the onset of a mobility gap in
      the device is observed. Although the computed asymmetries are not sufficient to
      warrant proper device operation, our results represent an initial step in the
      direction of improved transfer characteristics and, in particular, the developed
      simulation strategy is a powerful new tool for modeling doped graphene
      nanostructures.

PMID- 22876867
TI  - Nation-scale adoption of new medicines by doctors: an application of the Bass
      diffusion model.
AB  - BACKGROUND: The adoption of new medicines is influenced by a complex set of
      social processes that have been widely examined in terms of individual
      prescribers' information-seeking and decision-making behaviour. However,
      quantitative, population-wide analyses of how long it takes for new healthcare
      practices to become part of mainstream practice are rare. METHODS: We applied a
      Bass diffusion model to monthly prescription volumes of 103 often-prescribed
      drugs in Australia (monthly time series data totalling 803 million prescriptions
      between 1992 and 2010), to determine the distribution of adoption rates. Our aim
      was to test the utility of applying the Bass diffusion model to national-scale
      prescribing volumes. RESULTS: The Bass diffusion model was fitted to the adoption
      of a broad cross-section of drugs using national monthly prescription volumes
      from Australia (median R2 = 0.97, interquartile range 0.95 to 0.99). The median
      time to adoption was 8.2 years (IQR 4.9 to 12.1). The model distinguished two
      classes of prescribing patterns - those where adoption appeared to be driven
      mostly by external forces (19 drugs) and those driven mostly by social contagion
      (84 drugs). Those driven more prominently by internal forces were found to have
      shorter adoption times (p = 0.02 in a non-parametric analysis of variance by
      ranks). CONCLUSION: The Bass diffusion model may be used to retrospectively
      represent the patterns of adoption exhibited in prescription volumes in
      Australia, and distinguishes between adoption driven primarily by external forces
      such as regulation, or internal forces such as social contagion. The eight-year
      delay between the introduction of a new medicine and the adoption of the
      prescribing practice suggests the presence of system inertia in Australian
      prescribing practices.

PMID- 22876868
TI  - Differential equations models for interacting wild and transgenic mosquito
      populations.
AB  - We formulate and study continuous-time models, based on systems of ordinary
      differential equations, for interacting wild and transgenic mosquito populations.
      We assume that the mosquito mating rate is either constant, proportional to total
      mosquito population size, or has a Holling-II-type functional form. The focus is
      on the model with the Holling-II-type functional mating rate that incorporates
      Allee effects, in order to account for mating difficulty when the size of the
      total mosquito populations is small. We investigate the existence and stability
      of both boundary and positive equilibria. We show that the Holling-II-type model
      is the more realistic and, by means of numerical simulations, that it exhibits
      richer dynamics.

PMID- 22876869
TI  - A mathematical model for the dynamics of malaria in mosquitoes feeding on a
      heterogeneous host population.
AB  - We describe and develop a difference equation model for the dynamics of malaria
      in a mosquito population feeding on, infecting and getting infected from a
      heterogeneous population of hosts. Using the force of infection from different
      classes of humans to mosquitoes as parameters, we evaluate a number of
      entomological parameters, indicating malaria transmission levels, which can be
      compared to field data. By assigning different types of vector control
      interventions to different classes of humans and by evaluating the corresponding
      levels of malaria transmission, we can compare the effectiveness of these
      interventions. We show a numerical example of the effects of increasing coverage
      of insecticide-treated bed nets in a human population where the predominant
      malaria vector is Anopheles gambiae.

PMID- 22876870
TI  - Dynamics of a mechanistically derived stoichiometric producer-grazer model.
AB  - One of the simplest predator-prey models that tracks the quantity and the quality
      of prey is the one proposed by [I. Loladze, Y. Kuang, and J.J. Elser,
      Stoichiometry in producer-grazer systems: Linking energy flow with element
      cycling, Bull. Math. Biol. 62 (2000) pp. 1137-1162.] (LKE model). In it, the
      ratio of two essential chemical elements, carbon to phosphorus, C:P, represents
      prey quality. However, that model does not explicitly track P neither in the prey
      nor in the media that supports the prey. Here, we extend the LKE model by
      mechanistically deriving and accounting for P in both the prey and the media.
      Bifurcation diagrams and simulations show that our model behaves similarly to the
      LKE model. However, in the intermediate range of the carrying capacity,
      especially near the homoclinic bifurcation point for the carrying capacity,
      quantitative behaviour of our model is different. We analyze positive invariant
      region and stability of boundary steady states. We show that as the uptake rate
      of P by producer becomes infinite, LKE models become the limiting case of our
      model. Furthermore, our model can be readily extended to multiple producers and
      consumers.

PMID- 22876871
TI  - Evolution of specialization in resource utilization in structured
      metapopulations.
AB  - We study the evolution of resource utilization in a structured discrete-time
      metapopulation model with an infinite number of patches, prone to local
      catastrophes. The consumer faces a trade-off in the abilities to consume two
      resources available in different amounts in each patch. We analyse how the
      evolution of specialization in the utilization of the resources is affected by
      different ecological factors: migration, local growth, local catastrophes, forms
      of the trade-off and distribution of the resources in the patches. Our modelling
      approach offers a natural way to include more than two patch types into the
      models. This has not been usually possible in the previous spatially
      heterogeneous models focusing on the evolution of specialization.

PMID- 22876872
TI  - Dynamical analysis of a multi-strain model of HIV in the presence of anti
      retroviral drugs.
AB  - One major drawback associated with the use of anti-retroviral drugs in curtailing
      HIV spread in a population is the emergence and transmission of HIV strains that
      are resistant to these drugs. This paper presents a deterministic HIV treatment
      model, which incorporates a wild (drug sensitive) and a drug-resistant strain,
      for gaining insights into the dynamical features of the two strains, and
      determining effective ways to control HIV spread under this situation. Rigorous
      qualitative analysis of the model reveals that it has a globally asymptotically
      stable disease-free equilibrium whenever a certain epidemiological threshold (R t
      0) is less than unity and that the disease will persist in the population when
      this threshold exceeds unity. Further, for the case where R t 0 > 1, it is shown
      that the model can have two co-existing endemic equilibria, and competitive
      exclusion phenomenon occurs whenever the associated reproduction number of the
      resistant strain (R t r) is greater than that of the wild strain (R t w). Unlike
      in the treatment model, it is shown that the model without treatment can have a
      family of infinitely many endemic equilibria when its associated epidemiological
      threshold (R(0)) exceeds unity. For the case when [Formula in text], it is shown
      that the widespread use of treatment against the wild strain can lead to its
      elimination from the community if the associated reduction in infectiousness of
      infected individuals (treated for the wild strain) does not exceed a certain
      threshold value (in this case, the use of treatment is expected to make R t w < R
      t r.

PMID- 22876873
TI  - Campus drinking: an epidemiological model.
AB  - The drinking behaviours of college students have posed significant public health
      concerns for several generations. However, the dynamics of campus drinking have
      not been analysed using mathematical models. An epidemiological model capturing
      the dynamics of campus drinking is used to study how the 'disease' of drinking is
      spread on campus. The model suggests that the reproductive numbers are not
      sufficient to predict whether drinking behaviour will persist on campus and that
      the pattern of recruiting new members plays a significant role in the reduction
      of campus alcohol problems. In particular, campus alcohol abuse may be reduced by
      minimizing the ability of problem drinkers to directly recruit non-drinkers.

PMID- 22876874
TI  - Role of invariant water molecules and water-mediated ionic interactions in D
      xylose isomerase from Streptomyces rubiginosus.
AB  - The enzyme, D-xylose isomerase (D-xylose keto-isomerase; EC 5.3.1.5) is a soluble
      enzyme that catalyzes the conversion of the aldo-sugar D-xylose to the keto-sugar
      D-xylulose. A total of 27 subunits of D-xylose isomerase from Streptomyces
      rubiginosus were analyzed in order to identify the invariant water molecules and
      their water-mediated ionic interactions. A total of 70 water molecules were found
      to be invariant. The structural and/or functional roles of these water molecules
      have been discussed. These invariant water molecules and their ionic interactions
      may be involved in maintaining the structural stability of the enzyme D-xylose
      isomerase. Fifty-eight of the 70 invariant water molecules (83%) have at least
      one interaction with the main chain polar atom.

PMID- 22876875
TI  - Graphene enhanced electron transfer at aptamer modified electrode and its
      application in biosensing.
AB  - Graphene (GN), a two-dimensional and one-atom thick carbon sheet, is showing
      exciting applications because of its unique morphology and properties. In this
      work, a new electrochemical biosensing platform by taking advantage of the
      ultrahigh electron transfer ability of GN and its unique GN/ssDNA interaction was
      reported. Adenosine triphosphate binding aptamer (ABA) immobilized on Au
      electrode could strongly adsorb GN due to the strong pi-pi interaction and
      resulted in a large decrease of the charge transfer resistance (R(ct)) of the
      electrode. However, the binding reaction between ABA and its target adenosine
      triphosphate (ATP) inhibited the adsorption of GN, and R(ct) could not be
      decreased. On the basis of this, we developed a new GN-based biosensing platform
      for the detection of small molecule ATP. The experimental results confirmed that
      the electrochemical aptasensor we developed possessed a good sensitivity and high
      selectivity for ATP. The detection range for ATP was from 15 * 10(-9) to 4 * 10(
      3) M. The method here was label-free and sensitive and did not require
      sophisticated fabrication. Furthermore, we can generalize this strategy to detect
      Hg(2+) using a thymine (T)-rich, mercury-specific oligonucleotide. Therefore, we
      expected that this method may offer a promising approach for designing high
      performance electrochemical aptasensors for the sensitive and selective detection
      of a spectrum of targets.

PMID- 22876876
TI  - Effect of KRAS codon13 mutations in patients with advanced colorectal cancer
      (advanced CRC) under oxaliplatin containing chemotherapy. Results from a
      translational study of the AIO colorectal study group.
AB  - BACKGROUND: To evaluate the value of KRAS codon 13 mutations in patients with
      advanced colorectal cancer (advanced CRC) treated with oxaliplatin and
      fluoropyrimidines. METHODS: Tumor specimens from 201 patients with advanced CRC
      from a randomized, phase III trial comparing oxaliplatin/5-FU vs.
      oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations.
      Mutation data were correlated to response data (Overall response rate, ORR),
      progression-free survival (PFS) and overall survival (OS). RESULTS: 201 patients
      were analysed for KRAS mutation (61.2% males; mean age 64.2 +/- 8.6 years). KRAS
      mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon
      13). The ORR in codon 13 patients compared to codon 12 and wild type patients was
      significantly lower (p = 0.008). There was a tendency for a better overall
      survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all
      patients was not different in the three KRAS genetic groups (p = 0.72). However,
      we found a marked difference in PFS between patients with codon 12 and 13 mutant
      tumors treated with infusional 5-FU versus capecitabine based regimens.
      CONCLUSIONS: Our data suggest that the type of KRAS mutation may be of clinical
      relevance under oxaliplatin combination chemotherapies without the addition of
      monoclonal antibodies in particular when overall response rates are important.
      TRIAL REGISTRATION NUMBER: 2002-04-017.

PMID- 22876877
TI  - Writing on superhydrophobic nanopost arrays: topographic design for bottom-up
      assembly.
AB  - A well-known property of superhydrophobic surfaces, such as an array of
      hydrophobic nanoposts, is to allow only limited surface contact of a liquid to
      the tips of the nanoposts. Herein we demonstrate that material deposition from
      solution, whether solid precipitation, surface adsorption or colloidal adhesion
      in static system, or dynamic "writing", can be limited to these specific areas of
      the surface when in this nonwetting state. As an example of solid precipitation,
      we show that nucleation of CaCO(3) results in the growth of small, uniform,
      amorphous deposits (which can merge and recrystallize) instead of disordered,
      large crystals due to the abundance of identical, small heterogeneous nucleation
      sites. The growth of amorphous CaCO(3) can be used to trap molecules from
      solution, as a potential application for controlled drug release. To demonstrate
      the localized surface adsorption, we show that chemical functionalization of the
      post tips can make them "sticky" for specific attachment of species (such as
      colloidal particles) from solution. The electrostatic charge and relative size
      ratio of the particle/post diameters control the attachment of particles to the
      post tips with great specificity. Dynamic conditions have also been shown for
      writing using droplets translated across the nonwetting surface at controlled
      speeds during deposition. These methods offer unprecedented control over the
      heterogeneous nucleation and localized growth of crystals from solution and avoid
      nonspecific adsorption. There is selective control of colloidal or molecular
      attachment to the nanopost tips, whereby the contact area, time of contact, and
      tip surface chemistry for reaction are all independently tunable parameters.

PMID- 22876878
TI  - Environmental effects shape the maternal transfer of carotenoids and vitamin E to
      the yolk.
AB  - INTRODUCTION: Maternal effects occur when the phenotype of the offspring is
      influenced by the phenotype of the mother, which in turn depends on her heritable
      state as well as on influences from the current and past environmental
      conditions. All of these pathways may, therefore, form significant sources of
      variation in maternal effects. Here, we focused on the maternal transfer of
      carotenoids and vitamin E to the egg yolk, using canaries as a model species.
      Maternal yolk carotenoids and vitamin E are known to generate significant
      phenotypic variation in offspring, representing examples of maternal effects. We
      studied the intra-individual consistency in deposition patterns across two years
      and the mother-daughter resemblance across two generations in order to estimate
      the level of heritable variation. The effects of the current environmental
      conditions were studied via a food supplementation experiment, while the
      consequences of past environmental conditions were estimated on the basis of the
      early growth trajectories. RESULTS: There was a significant effect of the current
      environmental conditions on the yolk carotenoid and vitamin E deposition, but
      this effect varied between antioxidant components. The deposition of yolk
      carotenoids and vitamin E were linked to the process of yolk formation. Past
      environmental conditions did not contribute to the variation in yolk carotenoid
      and vitamin E levels nor did we find significant heritable variation.
      CONCLUSIONS: The transfer of carotenoids or vitamin E may be an example where
      current environmental variation is largely passed from the mother to the
      offspring, despite the numerous intermediate physiological steps that are
      involved. Differences in the effect of the environmental conditions as
      experienced by the mother during laying may be due to differences in availability
      as well as physiological processes such as competitive exclusion or selective
      absorption.

PMID- 22876879
TI  - Search for a small chromophore with efficient singlet fission: biradicaloid
      heterocycles.
AB  - Of the five small biradicaloid heterocycles whose S(1), S(2), T(1), and T(2)
      adiabatic excitation energies were examined by the CASPT2/ANO-L-VTZP method, two
      have been found to meet the state energy criterion for efficient singlet fission
      and are recommended to the attention of synthetic chemists and photophysicists.

PMID- 22876880
TI  - Stretch effects induced by molecular strain on weakening sigma-bonds: molecular
      design of long-lived diradicals (biradicals).
AB  - Stretch effects induced by two types of molecular strain were examined by quantum
      chemical calculations at the B3LYP/6-31G(d), B3LYP/cc-PVDZ, CCSD/6-31G(d), and
      CASPT2/ANO-RCC-VTZP level of theory, to design persistent multiradicals such as
      localized diradicals and oxyallyls. The cooperative molecular strain (Type-1)
      induced by the spiro[5.5]undecane and bicyclo[2.1.0]cyclopentane structures was
      found to significantly destabilize in energy the ring-closed compounds of the
      diradicals, leading to small energy differences between the diradicals and the
      sigma-bonded compounds. Another stretch effect (Type-2) induced by macrocyclic
      systems was also found to energetically destabilize the corresponding ring-closed
      structures of the 1,3-diradicals. The computational studies predict that the two
      types of stretch effects are quite effective in lowering the energy barriers of
      the bond-breaking reaction of the ring-closed compounds and in generating long
      lived localized diradicals and oxyallyl derivatives.

PMID- 22876881
TI  - Discovery and in vivo evaluation of dual PI3Kbeta/delta inhibitors.
AB  - Structure-based rational design led to the synthesis of a novel series of potent
      PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and
      selective PI3Kbeta/delta dual inhibitor that displayed suitable physicochemical
      properties and pharmacokinetic profile for animal studies. Analogue 63 was found
      to be efficacious in animal models of inflammation including a keyhole limpet
      hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of
      rheumatoid arthritis. These studies highlight the potential therapeutic value of
      inhibiting both the PI3Kbeta and delta isoforms in the treatment of a number of
      inflammatory diseases.

PMID- 22876882
TI  - Larval size in acanthocephalan parasites: influence of intraspecific competition
      and effects on intermediate host behavioural changes.
AB  - BACKGROUND: Parasites often face a trade-off between exploitation of host
      resources and transmission probabilities to the next host. In helminths, larval
      growth, a major component of adult parasite fitness, is linked to exploitation of
      intermediate host resources and is influenced by the presence of co-infecting
      conspecifics. In manipulative parasites, larval growth strategy could also
      interact with their ability to alter intermediate host phenotype and influence
      parasite transmission. METHODS: We used experimental infections of Gammarus pulex
      by Pomphorhynchus laevis (Acanthocephala), to investigate larval size effects on
      host behavioural manipulation among different parasite sibships and various
      degrees of intra-host competition. RESULTS: Intra-host competition reduced mean
      P. laevis cystacanth size, but the largest cystacanth within a host always
      reached the same size. Therefore, all co-infecting parasites did not equally
      suffer from intraspecific competition. Under no intra-host competition (1
      parasite per host), larval size was positively correlated with host phototaxis.
      At higher infection intensities, this relationship disappeared, possibly because
      of strong competition for host resources, and thus larval growth, and limited
      manipulative abilities of co-infecting larval acanthocephalans. CONCLUSIONS: Our
      study indicates that behavioural manipulation is a condition-dependant phenomenon
      that needs the integration of parasite-related variables to be fully understood.

PMID- 22876883
TI  - Longitudinal changes in patient-reported dyspnea in patients with COPD.
AB  - BACKGROUND: Although guidelines recommend monitoring symptoms in patients with
      chronic obstructive pulmonary disease (COPD), there is limited information on the
      longitudinal changes in patient-reported dyspnea (PRD) related to activities of
      daily living. The hypothesis was that PRD scores on the modified Medical Research
      Council (mMRC) scale, the self-administered computerized (SAC) transition dyspnea
      index (TDI), and the University of California San Diego Shortness of Breath
      questionnaire (UCSD SOBQ) would demonstrate progression over two years. METHODS:
      Observational cohort study of symptomatic patients with stable COPD evaluated
      every 6 months for 2 years. Patients rated the impact of activities of daily
      living on dyspnea using three patient-reported instruments presented in random
      order, and then performed post-bronchodilator (pBD) spirometry. RESULTS: Seventy
      patients (37 female/33 male; age: 66 +/- 9 years; and pBD forced expiratory
      volume in one second [(FEV1): 51 +/- 16% predicted] participated. Using fixed
      effects regression modeling, there was significant worsening in the PRD scores
      with the SAC TDI (-0.9 +/- 2.7; p = 0.03) and UCSD SOBQ (+5.7 +/- 18.3; p =
      0.001), but not with the mMRC scale (p = 0.52). Both pBD FEV1 (p = 0.19) and pBD
      forced vital capacity (p = 0.65) were unchanged. CONCLUSIONS: Multidimensional
      instruments (SAC TDI and UCSD SOBQ) demonstrated the frequently observed decline
      in PRD experienced by patients with COPD. The progression in PRD occurred despite
      stable lung function. Monitoring PRD provides unique clinical information and
      should be considered along with measuring lung function to assess patient status
      over time.

PMID- 22876884
TI  - The diagnosis of gestational diabetes mellitus: new paradigms or status quo?
AB  - The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study showed significant
      perinatal risks at levels of maternal hyperglycemia below values that are
      diagnostic for diabetes. A Consensus Panel of the International Association of
      Diabetes and Pregnancy Study Groups (IADPSG) reviewed HAPO Study results and
      other work that examined associations of maternal glycemia with perinatal and
      long-term outcomes in offspring and published recommendations for diagnosis and
      classification of hyperglycemia in pregnancy in 2010. Subsequently, some
      commentaries and debate challenged the IADPSG recommendations. In this review, we
      provide details regarding some points that were considered by the IADPSG
      Consensus Panel but not published and address the following issues: 1) what
      should be the frequency of gestational diabetes mellitus (GDM); 2) were
      appropriate outcomes and odds ratios used to define diagnostic thresholds for
      GDM; 3) to improve perinatal outcome, should the focus be on GDM, obesity, or
      both; 4) should results of randomized controlled trials of treatment of mild GDM
      influence recommendations for diagnostic thresholds; and, 5) other issues related
      to diagnosis of GDM. Other groups are independently considering strategies for
      the diagnosis of GDM. However, after careful consideration of these issues, we
      affirm our support for the recommendations of the IADPSG Consensus Panel.

PMID- 22876885
TI  - Altering the interfacial activation mechanism of a lipase by solid-phase
      selective chemical modification.
AB  - This study presents a combined protein immobilization, directed mutagenesis, and
      site-selective chemical modification approach, which was used to create a
      hyperactivated semisynthetic variant of BTL2. Various alkane chains were tethered
      at three different positions in order to mimic the lipase interfacial activation
      exogenously triggered by detergents. Optimum results were obtained when a
      dodecane chain was introduced at position 320 by solid-phase site-selective
      chemical modification. The resulting semisynthetic variant showed a 2.5-fold
      higher activity than the wild-type nonmodified variant in aqueous conditions.
      Remarkably, this is the maximum hyperactivation ever observed for BTL2 in the
      presence of detergents such as Triton X-100. We present evidence to suggest that
      the endogenous dodecane chain hyperactivates the enzyme in a similar fashion as
      an exogenous detergent molecule. In this way, we also observe a faster
      irreversible enzyme inhibition and an altered detergent sensitivity profile
      promoted by the site-selective chemical modification. These findings are also
      supported by fluorescence studies, which reveal that the structural conformation
      changes of the semisynthetic variant are different to those of the wild type, an
      effect that is more pronounced in the presence of detergent. Finally, the optimal
      immobilized semisynthetic variant was successfully applied to the selective
      synthesis of oxiran-2-yl butyrate. Significantly, this biocatalyst is 12-fold
      more efficient than the immobilized wild-type enzyme, producing the S-enantiomer
      with higher enantiospecificity (ee = 92%).

PMID- 22876886
TI  - Recent advances in the development of thioredoxin reductase inhibitors as
      anticancer agents.
AB  - Redox homeostasis is crucial for the cellular viability and normal function which
      balance is maintained by two major cellular antioxidant systems, including
      glutathione system and thioredoxin system. Thioredoxin system, including
      thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH, exhibits a wide range
      of functions such as regulation of redox state and cell apoptosis. Particularly,
      Trx functions as a protein disulfide reductase which is essential for the
      function of Trx system. However, the bioactivity of Trx is closely dependent on
      its reducing form. According to the information, TrxR is the only cellular enzyme
      to catalyze the NADPH-dependent reduction of Trx. Besides the reduction of some
      protein disulfide like Trx, TrxR still has a broad substrate specificity to
      reduce some small molecules like 5, 5 '-dithiobis-2- nitrobenzoic acid (DTNB).
      The reduction of Trx or its own direct action towards its various substrates
      endows TrxR with a wide range of cellular functions. Recent studies have
      elucidated that TrxR was upregulated in many malignant tumors and inhibition of
      TrxR could prevent the tumor initiation and progression, suggesting TrxR to be a
      promising target for cancer therapy and the high nucleophilic and accessible
      selenocysteine (Sec) active site might be the prime target for drug design.
      Various kinds of TrxR inhibitors have been developed as anticancer agents for
      years. In this review, TrxR inhibitors are divided into three classes, including
      metal-containing inhibitors, naturally occurring products and their derivatives
      and other newly emerged inhibitors. The last five years reports about TrxR
      inhibitors of each class will be introduced and their novel inhibiting mechanisms
      will be discussed.

PMID- 22876887
TI  - Co-morbidity and self medication in schizophrenia: involvement of endogenous
      morphine signaling mechanisms.
AB  - For over 30 years, empirical studies have demonstrated expression of chemically
      authentic morphine by diverse animal tissues and organs systems. De novo
      biosynthesis of endogenous morphine by animal cells displays striking
      similarities to the multi-enzyme mediated biosynthetic pathway previously
      characterized in great biochemical and molecular detail in opium poppy (Papaver
      somniferum). The committed enzyme step within this pathway involves an asymmetric
      Pictet-Spengler condensation of dopamine (DA) and 3,4 dihydroxyphenylacetaldehyde
      (DOPAL), the oxidation product of L- 3,4-dihydroxyphenylalanine (L-DOPA), to form
      the essential intermediate precursor tetrahydropapaveroline (THP). We have
      hypothesized that endogenous morphine is synthesized within peripheral sites via
      conversion of THP in a regulated biosynthetic pathway, or conversely, THP may be
      directly transported into the CNS and converted to endogenous morphine within a
      similar biosynthetic pathway. The fundamental chemical relationship of the
      prototype catecholamine DA and its immediate precursor L-DOPA to endogenous
      morphine expression indicates a novel reciprocally interactive mechanism that
      links catecholamine and "morphinergic" pathways in the activation and inhibition
      of key physiological responses, including higher order neural integration.
      Dysregulation of interactive DAergic and "morphinergic" signaling pathways within
      CNS foci may contribute to the etiological factors driving co-morbid behavioral
      syndromes in major psychiatric disorders. Our short review is designed to provide
      insights on comorbidity and self-medication in schizophrenia from a novel
      perspective involving endogenous morphine signaling mechanisms.

PMID- 22876888
TI  - Recent approaches to novel antibacterials designed after LPS structure and
      biochemistry.
AB  - Lipopolysaccharides (LPSs), which constitute the lipid portion of the outer
      leaflet of Gram-negative bacteria, are essential for growth, and are responsible
      for a variety of biological effects associated with Gram-negative sepsis. LPSs
      are amphiphilic molecules comprising three regions: lipid A, the core region, and
      a polysaccharide portion; the lipid A was proven to represent the toxic principle
      of endotoxic active lipopolysaccharides. In addition, it is known that the
      minimal conserved structure of LPS is the lipophylic oligoasaccharidic structure
      containing Kdo residues linked to the-LipA moiety. Thus, the design and
      development of novel antibacterial drugs can focus on different aspects, related
      to the biosynthesis and chemical features of LPS: 1) Inhibitors of lipid A
      biosynthesis 2) Inhibitors of Kdo biosynthesis. Both Kdo and Lipid A are needed
      for the construction of the minimum structural element Kdo2-LipidA, needed for
      bacterial survival. Any inhibitors acting on the biogenetic pathway of this
      molecule can act as antibacterial. 3) Antagonists of the interaction between
      endotoxins and the host receptors: LPS is recognised by the CD14 and the Toll
      like receptor (TLR)-4/MD2 complex, where Lipid A is the crucial moiety in the
      interaction. Any drug acting as an antagonist of this process can have antisepsis
      potential. Considerable efforts have been made in this direction to identify
      natural or synthetic molecules able to interfere with the interaction between LPS
      and inflammatory cells. This review will highlight recent efforts in the design
      and biological activity of enzyme inhibitors and antagonist acting on the 3 key
      aspects outlined above.

PMID- 22876889
TI  - Deleted in Colorectal Cancer (DCC) pathfinding: axon guidance gene finally turned
      tumor suppressor.
AB  - Loss of heterozygosity (LOH) at human chromosome 18q, which includes the gene
      Deleted in Colorectal Cancer (DCC), has been linked to colorectal and many other
      human cancers. DCC encodes the receptor for the axon guidance molecule Netrin
      (Net) and functions during neural development in a variety of organisms. However,
      since its discovery in the 1990s, the status of DCC as a tumor suppressor has
      been debated, primarily due to a lack of support for this hypothesis in animal
      models. A recent study from our laboratory capitalized on the genetic
      tractability of Drosophila melanogaster to demonstrate that this gene functions
      as an invasive tumor suppressor, thereby providing the first direct link between
      DCC loss and metastatic phenotypes in an animal model for cancer. Two subsequent
      studies from other laboratories have demonstrated that DCC suppresses tumor
      progression and metastasis in murine colorectal and mammary tumor models.
      Combined, these findings have prompted the rebirth of DCC as a tumor suppressor
      and highlighted the need for continued analysis of DCC function in animal models
      for human cancer.

PMID- 22876891
TI  - Review of extradepartmental pathology diagnoses: good medicine? Good investment?

PMID- 22876890
TI  - AtlasT4SS: a curated database for type IV secretion systems.
AB  - BACKGROUND: The type IV secretion system (T4SS) can be classified as a large
      family of macromolecule transporter systems, divided into three recognized sub
      families, according to the well-known functions. The major sub-family is the
      conjugation system, which allows transfer of genetic material, such as a
      nucleoprotein, via cell contact among bacteria. Also, the conjugation system can
      transfer genetic material from bacteria to eukaryotic cells; such is the case
      with the T-DNA transfer of Agrobacterium tumefaciens to host plant cells. The
      system of effector protein transport constitutes the second sub-family, and the
      third one corresponds to the DNA uptake/release system. Genome analyses have
      revealed numerous T4SS in Bacteria and Archaea. The purpose of this work was to
      organize, classify, and integrate the T4SS data into a single database, called
      AtlasT4SS - the first public database devoted exclusively to this prokaryotic
      secretion system. DESCRIPTION: The AtlasT4SS is a manual curated database that
      describes a large number of proteins related to the type IV secretion system
      reported so far in Gram-negative and Gram-positive bacteria, as well as in
      Archaea. The database was created using the RDBMS MySQL and the Catalyst
      Framework based in the Perl programming language and using the Model-View
      Controller (MVC) design pattern for Web. The current version holds a
      comprehensive collection of 1,617 T4SS proteins from 58 Bacteria (49 Gram
      negative and 9 Gram-Positive), one Archaea and 11 plasmids. By applying the bi
      directional best hit (BBH) relationship in pairwise genome comparison, it was
      possible to obtain a core set of 134 clusters of orthologous genes encoding T4SS
      proteins. CONCLUSIONS: In our database we present one way of classifying
      orthologous groups of T4SSs in a hierarchical classification scheme with three
      levels. The first level comprises four classes that are based on the organization
      of genetic determinants, shared homologies, and evolutionary relationships: (i) F
      T4SS, (ii) P-T4SS, (iii) I-T4SS, and (iv) GI-T4SS. The second level designates a
      specific well-known protein families otherwise an uncharacterized protein family.
      Finally, in the third level, each protein of an ortholog cluster is classified
      according to its involvement in a specific cellular process. AtlasT4SS database
      is open access and is available at http://www.t4ss.lncc.br.

PMID- 22876893
TI  - Selective serotonin reuptake inhibitors in pregnancy.
AB  - The use of antidepressant drugs, such as selective serotonin reuptake inhibitors
      (SSRIs), during pregnancy is rapidly increasing. To date, the effects of SSRI on
      pregnant women and fetuses are controversial and still a matter of debate.
      Although a number of studies have shown that these antidepressants are not
      teratogenic, some of them have reported an increase of congenital malformations
      after antenatal exposure to SSRIs. Moreover, fetal behavior is affected by these
      drugs, 30% of infants suffer from neonatal withdrawal symptoms and long term
      sequelae have not yet been excluded. Since there are no clear guidelines for SSRI
      treatment in pregnancy, potential risks must be balanced against the effects of
      untreated maternal depression. Treatment with SSRIs before and during pregnancy
      should only be considered in case of real necessity. Milder forms of depression
      should be treated with alternative methods. In this paper we have reviewed the
      literature on effects of SSRIs on embryonic, fetal and infant development.

PMID- 22876894
TI  - Mechanisms of fetal and neonatal renal impairment by pharmacologic inhibition of
      angiotensin.
AB  - The renin-angiotensin system is highly conserved through evolutionary history,
      and has multiple functions in addition to maintaining cardiovascular homeostasis:
      these include the regulation of renal cell survival and cell death, and
      development of the kidney. The importance of angiotensin (ANG) in normal kidney
      development was first recognized in infants with renal maldevelopment born to
      mothers treated with angiotensin converting enzyme (ACE) inhibitors or with ANG
      AT1 receptor blockers. The molecular role of ANG in renal development has been
      elucidated using gene targeting in mice, revealing major effects in branching
      morphogenesis, vasculogenesis, development of the papilla and renal concentrating
      mechanism. Although exposure of the fetus to ANG inhibitors is potentially
      harmful throughout pregnancy, effects are greater in late compared to early
      gestation. Significant differences between humans and rodents in placental
      transfer of ANG and timing of renal development contributed to initial delays in
      recognizing the teratogenic effects of ANG inhibitors. Although administration of
      ACE or AT1 receptor inhibitors can slow progression of renal disease in older
      children, ANG inhibition in the neonatal period can aggravate renal injury due to
      congenital urinary tract obstruction. Neonates are also far more sensitive than
      older children to the hypotensive actions these agents and doses must be markedly
      reduced to avoid precipitating oliguria. Understanding the complex interactions
      of the maturing renin-angiotensin system in the perinatal period is essential in
      the use of ANG or renin inhibitors in women during childbearing years or in
      neonates with cardiovascular or renal disease.

PMID- 22876895
TI  - Anticoagulant therapy during pregnancy for maternal and fetal acquired and
      inherited thrombophilia.
AB  - Thromboembolism is an infrequent, yet serious cause of both maternal and fetal
      morbidity and death during pregnancy and the puerperium. Antithrombotic treatment
      and prophylaxis both before and during pregnancy are based on unfractionated
      heparin (UH), low-molecularweight heparin (LMWH), Warfarin and Aspirin. The
      prevalence and severity of thromboembolism during pregnancy and puerperium
      warrant special consideration of management and therapy. Such therapy includes
      the treatment of acute thrombotic events and prophylaxis for those at increased
      risk of thrombotic events. This paper assesses the safety and efficacy of
      antithrombotic therapy during pregnancy and the peripartum period. Its
      cardiovascular and obstetric indications, the evidence of association between
      thrombophilias and adverse pregnancy outcome, regimens and maternal and fetal
      side-effects are also discussed.

PMID- 22876896
TI  - A developmental approach to drug-induced liver injury in newborns and children.
AB  - The liver represents the major site of drug metabolism in humans. The
      developmental changes that occur in the liver's metabolic activity during fetal
      life and in the perinatal period are at the basis of the varied sensitivity of
      human newborns to many drugs. The decreased capacity of the fetal and newborn
      liver to metabolize, detoxify, and excrete drugs--total cytochrome P450 content
      in the fetal liver being 30% to 60% of adult values--may explain the prolonged
      actions of many drugs in the newborn, as well as less their potential toxicity.
      On the other hand, the low levels of phase I (activation) enzymes, producing more
      polar reactive and often toxic metabolites, could explain the lower incidence of
      adverse effects of some drugs reported in newborns. Moreover, the greater
      capacity of newborns to synthesize glutathione is at the basis of their ability
      in inactivating many toxic metabolites. Here we review the acute and chronic
      liver toxicity due to the most widely used drugs in the neonate. We will discuss
      in detail the biochemical profile of the fetal and neonatal liver, and the toxic
      metabolites formed during the metabolism of the most widely used drugs in the
      neonate. The histological picture of liver disease related to the therapeutic use
      of drugs will be discussed, with particular emphasis on the mode of cell death
      involved in hepatitis induced by different drugs most frequently utilized in the
      neonatal intensive care units.

PMID- 22876897
TI  - Drugs in newborn resuscitation: the more we learn the least we use.
AB  - Temperature control, airway management and support of circulation remain the gold
      standards for the majority of neonates requiring resuscitation at birth. For the
      minority of neonates in which the basic steps of resuscitation fail to reverse an
      adverse situation, drug administration is justifiable. The 2010 International
      Liaison Committee on Resuscitation (ILCOR) guidelines for newborn resuscitation
      state: "Drugs are rarely indicated in resuscitation of the newly born infant.
      Bradycardia in the newborn infant is usually caused by inadequate lung inflation
      or profound hypoxia, and establishing adequate ventilation is the most important
      step to correct it. However, if the HR remains less than 60 min-1 despite
      adequate ventilation and chest compressions, it is reasonable to consider the use
      of drugs. These are best given via an umbilical venous catheter". Even though
      drugs have been used in neonatal resuscitation for long, their doses, order and
      route of administration have been issues of debate among neonatologists, mainly
      due to the lack of data in human studies. This review will examine existing
      evidence behind the medications currently used in neonatal resuscitation.

PMID- 22876899
TI  - Pharmacokinetics of antifungal agents in neonates and young infants.
AB  - The prevention and treatment of pediatric fungal infections are limited by the
      fact that not all antifungal drugs are approved for the pediatric age and
      appropriate dosages have not been established for each age group. The management
      of neonates and infants with invasive fungal infection is becoming more complex
      with an increasing number of antifungal agents available. Dosing information, is
      not available for newer antifungals and is limited with older antifungal agents.
      Insufficient neonatal studies have been performed with newer agents and there are
      numerous differences between neonates, children and adults with invasive fungal
      infection. Kinetic parameters such as the half-life [t(1/2)], clearance [CL], and
      volume of distribution [Vd] change with development, therefore the kinetics of
      antifungals need to be studied in order to optimize therapy with these drugs. A
      reasonable aim of pediatric dosing is to ensure levels of drug exposure which are
      comparable to those achievable in adults and which approximate those for which
      antifungal efficacy has been established. Therefore it will be of clinical
      relevance to ascertain the dosages of antifungals which produce an equivalent
      magnitude of exposure to that observed in adults. Drug therapy, studies on
      prescription and dosing should consider differences between neonates, infants and
      toddlers, children and adolescents in terms of drug disposition: absorption,
      metabolism and elimination/excretion. Determining the safety and pharmacokinetics
      of antifungals in neonates addresses an unfulfilled medical need given that data
      are sparse in neonates; at present, reports of antifungal pharmacokinetics in the
      treatment of neonatal fungal infections are limited to case series. The aim of
      this article is to review the pharmacokinetics of old and new antifungal drugs in
      neonates and young infants in a single article in order to provide a critical
      analysis of the literature. It will be important to evaluate all newly developed
      antifungals in neonates and infants to assure their maximum efficacy and safety.
      More pharmacokinetic data are required to ensure that the dose recommended for
      the treatment of fungal infections in the neonate achieves evidence based
      medicine.

PMID- 22876898
TI  - Fluconazole pharmacokinetics and safety in premature infants.
AB  - Invasive candidiasis (IC) in the premature infant population is a common
      infection that results in substantial morbidity and mortality. For these
      patients, fluconazole is among the first line therapies to treat and prevent IC,
      and yet few prospective studies investigating its pharmacokinetics (PK) and
      safety have been performed in this vulnerable population. We review five phase I
      studies examining the PK of fluconazole in premature infants, which demonstrate
      markedly differing kinetics compared to adults. Based on these data, a treatment
      dose of 12 mg/kg/day, with the potential need of a loading dose of 25 mg/kg to
      achieve rapid steady state concentrations, achieves surrogate pharmacodynamic
      targets. Additionally, fluconazole appears to be safe to use in this population,
      with only minimal reversible hepatobiliary effects.

PMID- 22876900
TI  - Vasoactive compounds in the neonatal period.
AB  - Sufficient organ blood flow of healthy newborn babies is maintained by relatively
      low systemic blood pressure. Premature infants are at an increased risk of
      systemic hypotension, often but not obviously, resulting in hypoperfusion of the
      cerebral, renal and intestinal vascular beds. Maintaining a stable blood pressure
      in preterm babies is of high importance in order to prevent complications such as
      intraventricular hemorrhage, periventricular leucomalatia, necrotizing
      enterocolitis or renal failure. The regulation of systemic and local hemodynamics
      in newborns differs substantially from that of the adults. Developmental changes
      in catecholamine sensitivity, higher local vasodilator factor activity and
      structural differences of the immature myocardium should be taken into account
      when applying vasoactive agents in neonates. The effects of widely used
      catecholamines such as dopamine, epinephrine or dobutamine can not be directly
      adapted from adult therapeutics to neonatal care. Their administration should be
      supported by data on their effects on systemic and cerebral blood flow in
      addition to blood pressure changes. At the bedside, neonatologists should use new
      diagnostic tools to differentiate between neonatal hypotension and hypoperfusion,
      vasoconstriction and myocardial dysfunction in order to choose the appropriate
      medication. Newer vasoactive agents already used in adult or pediatric
      cardiovascular therapy such as milrinone, levosimendan or terlipressin need to be
      carefully evaluated before introducing them to the treatment of neonatal
      hypotensive states. Well-designed preclinical and human newborn studies also
      evaluating their local effects are warranted.

PMID- 22876901
TI  - Therapeutic strategies in pulmonary hypertension of the newborn: where are we
      now?
AB  - Despite recent advances, Persistent Pulmonary Hypertension of the Newborn (PPHN)
      still represents an important challenge for neonatologists. The care of newborns
      with PPHN requires meticulous therapeutic and ventilation strategies including,
      besides the stabilization of the newborn, the use of selective pulmonary
      vasodilators as inhaled Nitric Oxide (iNO). However, not all the neonates with
      PPHN are responsive to this clinical approach. Recent studies have proposed the
      use of alternative therapies to iNO, when it is not available, or there is no or
      only a transitory response. Sildenafil, a phosphodiesterase 5 inhibitor, appears
      as a frequent used therapy in refractory forms of PPHN. The aim of this review is
      to analyze the current therapeutic strategies in PPHN with special emphasis on
      iNO.

PMID- 22876902
TI  - Nenatal drug induced nephrotoxicity : old and next generation biomarkers for
      early detection and management of neonatal drug-induced nephrotoxicity, with
      special emphasis on uNGAL and on metabolomics.
AB  - For a long time, nephrotoxicity has been definitively defined as renal injury or
      dysfunction that arises as a direct or indirect result of exposure to drugs and
      industrial or environmental chemicals. There are a number of inherent
      difficulties in diagnostic procedures for toxic nephropathy, which include the
      absence of standard diagnostic criteria and the inability to relate exposure to a
      given agent and the observed effect. Critically ill newborns represent a high
      risk population for developing toxic nephropathy because of incomplete maturation
      of the kidney; furthermore, they are often treated with a combination of various
      therapeutic agents, each of them potentially inducing renal tissue injury.
      Antibiotics, antifungals, and non-steroidal antiiflammatory drugs (NSAIDs) can
      induce nephrotoxic damage by several, concomitant mechanisms of action on
      different segments of the nephron. The most common clinical feature following a
      nephrotoxic effect is acute kidney injury (AKI) which, in turn, comprises a
      spectrum of severe tissue damages along the nephron, leading to an abrupt decline
      in renal function. Because early stages of toxic nephropathy are characterized by
      very few specific clinical signs and symptoms, there is the urgent need to
      investigate new biomarkers for predicting nephrotoxicity and localizing the
      injury to a specific nephron site, in order to reduce the risk of acute renal
      injury and/or acute tubular necrosis. The most promising biomarker for the early
      assessment of kidney injury and damage is neutrophil gelatinase-associated
      lipocalin (NGAL). NGAL can be easily measured in urine by an automated analytical
      method, allowing its clinical use in emergency likewise creatinine. Considerable
      expectations in terms of improvement of the management of newborns developing
      drug-induced nephropaties derive from the clinical application of metabolomics.

PMID- 22876903
TI  - Review metabolomics: a new approach to drug delivery in perinatology.
AB  - The purpose of this review is to describe the state of the art of the
      pharmacological applications in perinatal medicine and highlight how a new
      emerging discipline, metabolomics, may have a significant impact on understanding
      complex biological processes associated with the drugs actions. Currently, there
      is great demand for new information regarding the use of drugs, especially during
      the perinatal period in order to minimize the occurrence of adverse drug
      reactions and to maximize the desired therapeutic effect. Metabolomics is a
      functional genomic tool concerned with the high-throughput identification,
      quantification and characterization of small molecule metabolites. This new
      technique has been shown to have a great impact on classifying phenotypes,
      investigation of physiological status, diagnosing disease, measuring the response
      to treatment, discovering biomarkers, and identifying perturbed pathways due to
      disease or treatment. Metabolic profiles appear to be a key factor in predicting
      the outcome of a pathological condition and the individual's response to a
      pharmacological treatment. This new systems biology tool may have important
      potential implication for pharmacological science, in particular drug discovery,
      development, and prediction of the drug's effects on the body by explaining the
      mechanisms by which drug response causes adverse effects.

PMID- 22876904
TI  - A stochastic model of a cell population with quiescence.
AB  - A cell population in which cells are allowed to enter a quiescent
      (nonproliferating) phase is analyzed using a stochastic approach. A general
      branching process is used to model the population which, under very mild
      conditions, exhibits balanced exponential growth. A formula is given for the
      asymptotic fraction of quiescent cells, and a numerical example illustrates how
      convergence toward the asymptotic fraction exhibits a typical oscillatory
      pattern. The model is compared with deterministic models based on semigroup
      analysis of systems of differential equations.

PMID- 22876905
TI  - A stochastic SIR model with contact-tracing: large population limits and
      statistical inference.
AB  - This paper is devoted to the presentation and study of a specific stochastic
      epidemic model accounting for the effect of contact-tracing on the spread of an
      infectious disease. Precisely, one considers here the situation in which
      individuals identified as infected by the public health detection system may
      contribute to detecting other infectious individuals by providing information
      related to persons with whom they have had possibly infectious contacts. The
      control strategy, which consists of examining each individual who has been able
      to be identified on the basis of the information collected within a certain time
      period, is expected to efficiently reinforce the standard random-screening-based
      detection and considerably ease the epidemic. In the novel modelling of the
      spread of a communicable infectious disease considered here, the population of
      interest evolves through demographic, infection and detection processes, in a way
      that its temporal evolution is described by a stochastic Markov process, of which
      the component accounting for the contact-tracing feature is assumed to be valued
      in a space of point measures. For adequate scalings of the demographic, infection
      and detection rates, it is shown to converge to the weak deterministic solution
      of a PDE system, as a parameter n, interpreted as the population size, roughly
      speaking, becomes larger. From the perspective of the analysis of infectious
      disease data, this approximation result may serve as a key tool for exploring the
      asymptotic properties of standard inference methods such as maximum likelihood
      estimation. We state preliminary statistical results in this context. Eventually,
      relations of the model with the available data of the HIV epidemic in Cuba, in
      which country a contact-tracing detection system has been set up since 1986, is
      investigated and numerical applications are carried out.

PMID- 22876906
TI  - Discrete three-stage population model: persistence and global stability results.
AB  - A general three-stage discrete-time population model is studied. The inherent net
      reproductive number for this model is derived. Global stability of the origin is
      established provided that the inherent net reproductive number is less than one.
      If it is larger than one the existence of a unique positive fixed point is proved
      and the persistence of the system is established. Finally, for certain parameter
      ranges global stability of the positive fixed point is proved.

PMID- 22876907
TI  - Bifurcation structure of a chemostat model for an age-structured predator and its
      prey.
AB  - We model a chemostat containing an age-structured predator and its prey using a
      linear function for the uptake of substrate by the prey and two different
      functional responses (linear and Monod) for the consumption of prey by the
      predator. Limit cycles (LCs) caused by the predator's age structure arise at Hopf
      bifurcations at low values of the chemostat dilution rate for both model cases.
      In addition, LCs caused by the predator-prey interaction arise for the case with
      the Monod functional response. At low dilution rates in the Monod case, the age
      structure causes cycling at lower values of the inflowing resource concentration
      and conversely prevents cycling at higher values of the inflowing resource
      concentration. The results shed light on a similar model by Fussmann et al. [G.
      Fussmann, S. Ellner, K. Shertzer, and N. Hairston, Crossing the Hopf bifurcation
      in a live predator-prey system, Science 290 (2000), pp. 1358-1360.], which
      correctly predicted conditions for the onset of cycling in a chemostat containing
      an age-structured rotifer population feeding on algal prey.

PMID- 22876908
TI  - A note on persistence about structured population models.
AB  - In this paper, we report some results on persistence in two structured population
      models: a chronic- age-structured epidemic model and an age-duration-structured
      epidemic model. Regarding these models, we observe that the system is uniformly
      strongly persistent, which means, roughly speaking, that the proportion of
      infected subpopulation is bounded away from 0 and the bound does not depend on
      the initial data after a sufficient long time, if the basic reproduction ratio is
      larger than one. We derive this by adopting Thieme's technique, which requires
      some conditions about positivity and compactness. Although the compactness
      condition is rather difficult to show in general infinite-dimensional function
      spaces, we can apply Frechet-Kolmogorov L(1)-compactness criteria to our models.
      The two examples that we study illuminate a useful method to show persistence in
      structured population models.

PMID- 22876910
TI  - Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for
      one week and antiglaucoma effects for four days following one-time topical
      administration.
AB  - We report a novel hybrid polyamidoamine (PAMAM) dendrimer hydrogel/poly(lactic-co
      glycolic acid) (PLGA) nanoparticle platform (HDNP) for codelivery of two
      antiglaucoma drugs, brimonidine and timolol maleate. This platform was not
      cytotoxic to human corneal epithelial cells. Cellular uptake of Nile red
      encapsulating PLGA nanoparticles was significantly increased by dendrimer
      hydrogel. A prolonged residence time of nanoparticles was demonstrated through
      investigation of FluoSpheres loaded into dendrimer hydrogel. Both brimonidine and
      timolol maleate were slowly released in vitro over a period of 28-35 days.
      Following topical administration of one eye drop (30 MUL of 0.7% w/v brimonidine
      and 3.5% w/v timolol maleate) in normotensive adult Dutch-belted male rabbits,
      the HDNP formulation resulted in a sustained and effective IOP reduction (18% or
      higher) for 4 days. Furthermore, the HDNP maintained significantly higher
      concentrations of brimonidine in aqueous humor and cornea as well as timolol
      maleate in the aqueous humor, cornea, and conjunctiva up to 7 days as compared to
      saline, DH, and PLGA nanoparticle dosage forms, without inducing ocular
      inflammation or discomfort. Histological analysis of the cornea and conjunctiva
      did not reveal any morphological or structural changes. Our work demonstrated
      that this new platform is capable of enhancing drug bioavailability and
      sustaining effective IOP reduction over an extended period of time. This newly
      developed platform can greatly reduce dosing frequency of topical formulations,
      thus, improving long-term patient compliance and reducing enormous societal and
      economic costs. Given its high structural adaptability, many other chronic ocular
      diseases would benefit from long-lasting drug delivery of this new platform.

PMID- 22876911
TI  - Treatment of cognitive impairment in patients with multiple sclerosis.
AB  - INTRODUCTION: Identifying and treating cognitive impairment in patients with
      multiple sclerosis (MS) is increasingly recognized as a crucial step in selecting
      the most appropriate treatment for the individual. Currently, the
      neuropsychological tests used to assess patients are time-consuming and require
      specialist training to administer; consequently, cognitive impairment in MS is
      underdiagnosed. Many treatments are available for MS, including disease-modifying
      drugs (DMDs) and symptomatic therapies, but what are their effects on cognitive
      performance? AREAS COVERED: This article will review published studies describing
      the cognitive effects of DMDs and symptomatic treatments for MS. EXPERT OPINION:
      Some DMDs may improve cognitive performance in patients with MS. None of the
      symptomatic drug treatments reviewed showed positive effects on cognitive
      performance, with the possible exception of L-amphetamine, which may improve
      memory in patients with existing deficits, and methylphenidate, on which more
      data are needed. Cognitive rehabilitation can improve cognitive performance, but
      experience with these techniques is limited. Treatment for patients with MS and
      cognitive impairment should, therefore, include a DMD in combination with a
      pharmacological or perhaps non-pharmacological cognitive-enhancement strategy.
      However, the methods used to diagnose cognitive impairment, and to assess the
      effect of treatment on function over time and need to be refined.

PMID- 22876912
TI  - Factors influencing legacy pollutant accumulation in alpine osprey: biology,
      topography, or melting glaciers?
AB  - Persistent organic pollutants (POPs) can be transported long distances and
      deposited into alpine environments via cold trapping and snow scavenging
      processes. Here we examined biotic and abiotic factors determining contaminant
      variability of wildlife in alpine ecosystems. We measured POPs in eggs and plasma
      of an apex predator, the osprey (Pandion haliaetus) breeding in 15 mountainous
      watersheds across a broad latitudinal, longitudinal and altitudinal range in
      western Canada. After accounting for proximate biotic factors such as trophic
      level (delta(15)N) and carbon source (delta(13)C), variability in contaminant
      concentrations, including SigmaDDT (sum of trichlorodiphenylethane-related
      compounds), toxaphene, hexachlorobenzene (HCB), total chlordane, and SigmaPCBs
      (polychlorinated biphenyls) in osprey tissues was explained by interactions among
      relative size of watersheds, water bodies, elevation, and glacial input. SigmaDDT
      in nestling plasma, for example, decreased with lake elevation, probably as a
      result of local past inputs from agricultural or public health usage at lower
      altitude sites. In contrast, toxaphene, never used as an insecticide in western
      Canada, increased with elevation and year-round snow and ice cover in both plasma
      and eggs, indicating long-range atmospheric sources as dominant for toxaphene.
      Lower chlorinated PCBs in plasma tended to decrease with elevation and ice cover
      consistent with published data and model outcomes. Temporal trends of POPs in
      osprey eggs are coincident with some modeled predictions of release from melting
      glaciers due to climate change. Currently we suggest that contaminants largely
      are released through annual snowpack melt and deposited in large lower elevation
      lakes, or some smaller lakes with poor drainage. Our study highlights the
      importance of understanding how biological processes integrate physical when
      studying the environmental chemistry of wildlife.

PMID- 22876913
TI  - Structural dynamics of V3 loop with different electrostatics: implications on co
      receptor recognition: a molecular dynamics study of HIV gp120.
AB  - The HIV's envelope glycoprotein gp120 plays a major role in the entry of the
      virus into the host cell, through its successive interactions with the cell
      surface CD4 receptor and a co-receptor (CCR5 or CXCR4). The choice of a specific
      co-receptor by gp120 has an important consequence on HIV infection and
      pathogenesis. The third variable region within gp120, the V3 loop, is the
      principal determinant of the co-receptor usage by gp120. Here, we report the long
      time molecular dynamics simulations of four gp120 structures, having a V3 loop
      charge of +3 and +5, from both R5 and X4 specific strains of HIV. The results of
      the study highlight the properties of the V3 loop that can be critical for
      dictating the co-receptor recognition and selection in structural context. In
      detail, we observe that the structural orientation of the V3 loop in the 3D space
      is modulated by its net charge, whilst its co-receptor choice is likely dictated
      by a combined effect of both the electrostatics of the loop and its
      conformational variability at the level of its central crown region.

PMID- 22876914
TI  - Specificity and promiscuity in human glutaminase interacting protein recognition:
      insight from the binding of the internal and C-terminal motif.
AB  - A large number of cellular processes are mediated by protein-protein
      interactions, often specified by particular protein binding modules. PDZ domains
      make up an important class of protein-protein interaction modules that typically
      bind to the C-terminus of target proteins. These domains act as a scaffold where
      signaling molecules are linked to a multiprotein complex. Human glutaminase
      interacting protein (GIP), also known as tax interacting protein 1, is unique
      among PDZ domain-containing proteins because it is composed almost exclusively of
      a single PDZ domain rather than one of many domains as part of a larger protein.
      GIP plays pivotal roles in cellular signaling, protein scaffolding, and cancer
      pathways via its interaction with the C-terminus of a growing list of partner
      proteins. We have identified novel internal motifs that are recognized by GIP
      through combinatorial phage library screening. Leu and Asp residues in the
      consensus sequence were identified to be critical for binding to GIP through site
      directed mutagenesis studies. Structure-based models of GIP bound to two
      different surrogate peptides determined from nuclear magnetic resonance
      constraints revealed that the binding pocket is flexible enough to accommodate
      either the smaller carboxylate (COO(-)) group of a C-terminal recognition motif
      or the bulkier aspartate side chain (CH(2)COO(-)) of an internal motif. The
      noncanonical ILGF loop in GIP moves in for the C-terminal motif but moves out for
      the internal recognition motifs, allowing binding to different partner proteins.
      One of the peptides colocalizes with GIP within human glioma cells, indicating
      that GIP might be a potential target for anticancer therapeutics.

PMID- 22876916
TI  - It's the fracture that matters -bone disease in COPD patients.

PMID- 22876915
TI  - Functional expression of a penicillin acylase from the extreme thermophile
      Thermus thermophilus HB27 in Escherichia coli.
AB  - BACKGROUND: Penicillin acylases (PACs) are enzymes of industrial relevance in the
      manufacture of beta-lactam antibiotics. Development of a PAC with a longer half
      life under the reaction conditions used is essential for the improvement of the
      operational stability of the process. A gene encoding a homologue to Escherichia
      coli PAC was found in the genome of the thermophilic bacterium Thermus
      thermophilus (Tth) HB27. Because of the nature of this PAC and its complex
      maturation that is crucial to reach its functional heterodimeric final
      conformation, the overexpression of this enzyme in a heterologous mesophilic host
      was a challenge. Here we describe the purification and characterization of the
      PAC protein from Tth HB27 overexpressed in Escherichia coli. RESULTS: Fusions to
      a superfolder green fluorescent protein and differential membrane solubilization
      assays indicated that the native enzyme remains attached through its amino
      terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order
      to overexpress this PAC in E. coli cells, a variant of the protein devoid of its
      membrane anchoring segment was constructed. The effect of the co-expression of
      chaperones and calcium supplementation of the culture medium was investigated.
      The total production of PAC was enhanced by the presence of DnaK/J and GrpE and
      even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly
      improved both PAC specific and volumetric activities. Recombinant PAC was
      affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE
      and MALDI-TOF analysis of the subunits. The recombinant protein was tested for
      activity towards several penicillins, cephalosporins and homoserine lactones.
      Hydrophobic acyl-chain penicillins were preferred over the rest of the
      substrates. Penicillin K (octanoyl penicillin) was the best substrate, with the
      highest specificity constant value (16.12 mM-1.seg-1). The optimum pH was aprox.
      4 and the optimum temperature was 75  degrees C. The half-life of the enzyme at
      this temperature was 9.2 h. CONCLUSIONS: This is the first report concerning the
      heterologous expression of a pac gene from a thermophilic microorganism in the
      mesophilic host E. coli. The recombinant protein was identified as a penicillin K
      deacylating thermozyme.

PMID- 22876918
TI  - Editorial: adiponectin in health and disease: current evidence and therapeutic
      perspectives.

PMID- 22876919
TI  - Therapeutic perspectives for adiponectin: an update.
AB  - In obesity, the expansion of dysfunctional adipose tissue leads to augmented
      production of pro-inflammatory adipokines that mediate metabolic changes through
      their paracrine and/or endocrine actions. By contrast, the secretion and plasma
      concentration of adiponectin, an adipokine with cardiovascular protective, anti
      diabetic and anti-inflammatory properties, are markedly decreased in obesity and
      its related pathologies. Epidemiological studies on different ethnic groups have
      identified hypoadiponectinemia as an independent risk factor for type 2 diabetes,
      hypertension, coronary heart disease and several types of cancers. In animals,
      replenishment of recombinant adiponectin or transgenic expression of adiponectin
      can reverse these obesity-related pathological conditions. Although there is
      currently no direct clinical evidence demonstrating that adiponectin is effective
      in treating obesity-related cardiometabolic diseases, therapeutic benefits of
      several anti-diabetic and cardiovascular drugs, such as the agonists of
      peroxisome proliferator-activated receptor (PPAR) gamma and PPAR alpha and
      statins, are associated with increased plasma adiponectin in humans. In addition,
      a number of medicinal herbs and natural compounds with beneficial effects on
      cardiometabolic diseases, have been shown to increase adiponectin secretion in
      adipocytes. This review highlights recent advances on multiple beneficial effects
      of adiponectin and discusses the potential therapeutic interventions for obesity
      related cardiometabolic syndromes by targeting adiponectin.

PMID- 22876920
TI  - Structure, signalling and physiologic role of adiponectin-dietary and exercise-
      related variations.
AB  - Since its discovery in 1995 adiponectin has garnered considerable interest from
      the academic, clinical and biotech communities due to its proposed salutary anti
      inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. As
      a result our appreciation of adiponectin's structure and the importance of post
      translational modifications (PTMs) in adiponectin production are now relatively
      advanced. So too, following the identification of a variety of adiponectin
      receptors, binding proteins and downstream signalling networks, is our
      understanding of adiponectin's intracellular signalling pathways that are
      implicated in mediating adiponectin's pleiotropic effects. Adiponectin's ability
      to moderate inflammation, which is recognised as a key protagonist in many modern
      diseases, may be the key to many of its beneficial effects. Recent insights
      indicate that adiponectin modulates cellular inflammation by affecting
      sphingolipid metabolism, with the adiponectin receptors displaying intrinsic
      ceramidase activity. In the current review we will summarise the molecular
      details of adiponectin, discuss key players and recent insights into adiponectin
      signalling and consider the physiologic role(s) of adiponectin. We will also
      review studies into the effects of diet or exercise on circulating adiponectin
      levels focusing largely on reports from human trials.

PMID- 22876921
TI  - Adiponectin in pregnancy: implications for health and disease.
AB  - Pregnancy is a unique physiologic state that is associated with profound
      alterations in maternal metabolic, endocrine, and vascular function, designed to
      ensure the delivery of appropriate energy and nutrition to the developing fetus.
      In this context, the role of the fat-derived hormone adiponectin is of interest,
      particularly in light of emerging recognition of the broad array of physiologic
      processes upon which this adipokine impacts. Indeed, adiponectin has pleiotropic
      effects on the regulation of energy homeostasis, systemic inflammation, vascular
      function, cell growth, and even bone metabolism. Thus, in this review, we
      consider existing evidence for the physiologic role of adiponectin in human
      gestation and how this protein may be relevant to two major medical disorders of
      pregnancy: gestational diabetes mellitus and preeclampsia. While studies to date
      have yielded many conflicting findings pertaining to adiponectin in pregnancy,
      further investigation in this area is essential. Ultimately, elucidation of
      adiponectin physiology in the setting of both normal pregnancy and its pathologic
      conditions may provide unique insight into fundamental processes that are
      relevant to health and disease in mother and child.

PMID- 22876922
TI  - Adiponectin in diabetes mellitus.
AB  - Adiponectin represents one of the most abundant and well-studied adipokines that
      has been implicated as a major protective factor against the adverse metabolic
      and cardiovascular consequences of obesity. The main insulin-sensitizing action
      of adiponectin results from decrease in hepatic gluconeogenesis and increase in
      muscle glucose transport and, secondly from enhancement of energy consumption and
      fatty acid oxidation in peripheral tissues with the aim of increasing ATP
      production. Besides these effects, the potential role of adiponectin on insulin
      secretion, as well as on energy expenditure, through central action, has also
      been investigated. Accumulating evidence from clinical, experimental animal and
      genetic studies support a close association between hypoadiponectinemia and
      insulin resistance/ type 2 diabetes. The question that arises is whether
      hypoadiponectinemia is the result of insulin resistance/type 2 diabetes or the
      cause of this disorder. Based on the observation that various drug classes exert
      beneficial effects on insulin resistance partly by increasing plasma adiponectin
      levels, it could hypothesized that substances that enhance or mimic adiponectin
      to activate its receptors and/or postreceptor signaling pathway may be a
      promising therapeutic strategy in the prevention and treatment of diabetes.
      However, many questions need to be addressed before adiponectin can be used as a
      potent therapeutic target.

PMID- 22876923
TI  - Protective role of adiponectin in cardiovascular disease.
AB  - This review focuses on the recent findings that adiponectin plays a significant
      role of in cardiovascular diseases. Adipose tissue functions as an endocrine
      organ by secreting adipocytokines that can directly affect nearby or remote
      organs. Adiponectin is an adipocytokine whose concentration is down-regulated in
      subjects with obesity-related disorders. Low levels of circulating adiponectin
      appear to associate with the increased prevalence of obesity-linked diseases
      including atherosclerosis and ischemic heart disease. A number of experimental
      studies have shown that adiponectin exerts beneficial effects on the
      cardiovascular system by directly acting on the component cells in the heart and
      blood vessels. The cardiovascular protection by adiponectin is mediated through
      its ability to attenuate inflammatory responses and apoptotic activities in the
      target organs. Thus, adiponectin could represent a therapeutic target molecule
      for prevention or treatment of cardiovascular diseases.

PMID- 22876924
TI  - Adiponectin: key player in the adipose tissue-liver crosstalk.
AB  - The adipose tissue has recently emerged as an important endocrine organ releasing
      numerous mediators including adipocytokines, classical cytokines and others.
      Adiponectin, one of the major products of adipocytes, is a prototypic anti
      diabetic adipocytokine, the actions of which are mainly exerted by the activation
      of AMP-activated kinase and peroxisome proliferator-activated receptor alpha.
      This adipocytokine is one of the most abundant circulating (adipo)cytokines in
      health. Non-alcoholic fatty liver disease (NAFLD), the major reason for abnormal
      liver functions in the western world, is commonly associated with obesity,
      insulin resistance and decreased adiponectin serum levels. Adiponectin has many
      anti-inflammatory activities and suppresses tumour necrosis factor-alpha
      (TNFalpha), a cytokine of key importance in NAFLD. The anti-inflammatory effects
      of adiponectin are also exerted by induction of the anti-inflammatory cytokines
      interleukin-10 (IL-10) or IL-1 receptor antagonist and up-regulation of heme
      oxygenase-1. Whereas the liver probably is not a relevant source of circulating
      adiponectin, it is a major target organ for many adiponectin effects. Adiponectin
      is able to regulate steatosis, insulin resistance, inflammation and fibrosis.
      NAFLD is also associated with decreased liver expression of the two adiponectin
      receptors (AdipoR1 and 2) thereby contributing to a state of hepatic adiponectin
      resistance. In contrast, most other liver diseases especially in advanced disease
      states exhibit increased adiponectin serum levels with highest levels observed in
      cirrhosis. Targeting adiponectin could evolve as a major treatment concept
      especially for fatty liver diseases in the future.

PMID- 22876925
TI  - Adiponectin in autoimmune diseases.
AB  - Adiponectin is the most abundant adipokine circulating in the organism. Different
      molecular forms of adiponectin exist: low, middle and high molecular isoforms, as
      well as globular adiponectin, all of which have different biological properties.
      Adiponectin is considered a key adipokine in metabolic diseases such as type 2
      diabetes, metabolic syndrome and related complications, especially cardiovascular
      diseases. In these metabolic conditions, circulating adiponectin is reduced. It
      is now well known that adiponectin has beneficial effects on endothelial cells
      and endothelial function and is also cardioprotective. Unlike metabolic diseases,
      systemic autoimmune and chronic inflammatory joint diseases are characterized by
      increased production of adiponectin. There is evidence to suggest that
      adiponectin may be related to disease activity and/or severity in different
      conditions such as rheumatoid arthritis, systemic lupus erythematosus and
      osteoarthritis. Since adiponectin has been found to display both pro and anti
      inflammatory activities, controversial findings have been observed on the role of
      total adiponectin in systemic autoimmune and inflammatory joint diseases. Thus,
      the relative contribution of each adiponectin isoform to the inflammatory
      response and joint and/or tissue damage requires further study.

PMID- 22876926
TI  - Adiponectin in metabolic bone disease.
AB  - Adiponectin has attracted widespread attention because of its pivotal role in
      glucose metabolism and energy homeostasis. Adiponectin and its receptor are shown
      to be expressed in osteoblasts, suggesting that adiponectin might affect bone
      metabolism. A number of clinical studies have shown that serum adiponectin is
      negatively associated with bone mineral density (BMD) and positively with
      biochemical markers of bone turnover, suggesting that adiponectin may be a
      negative regulator of bone mass. However, most in vitro studies demonstrate that
      adiponectin stimulates the differentiation and mineralization of osteoblasts as
      well as the expression of osteocalcin. Adiponectin indirectly stimulates
      osteoclast differentiation via receptor activator for nuclear factor kappaB
      ligand and osteoprotegerin expression in osteoblasts, while adiponectin directly
      inhibits osteoclast activity and bone resorption. These in vitro findings suggest
      that adiponectin stimulates bone formation and remodeling as well as inhibits
      bone resorption. In contrast, previous in vivo studies using overexpression and
      knockout mice of adiponectin have produced controversial results. On the other
      hand, recent studies have shown that osteocalcin derived form osteoblasts acts as
      a hormone regulating glucose metabolism and fat mass. Osteocalcin could decrease
      fat pads and stimulate the expression of adiponectin in adipocytes, suggesting
      that bone metabolism is associated with fat metabolism through adiponectin and
      osteocalcin. In this review, I summarize the effect of adiponectin on osteoblasts
      and osteoclasts in vitro and in vivo, the association of adiponectin with BMD and
      bone markers in humans, and the role of adiponectin in the endocrine loop between
      bone and fat metabolism.

PMID- 22876927
TI  - Adiponectin in pulmonary disease and critically ill patients.
AB  - Adiponectin is a predominantly anti-inflammatory protein produced by adipose
      tissue with possible signalling activity in the lung. It is increasingly
      associated with inflammatory pulmonary diseases, such as asthma and chronic
      obstructive pulmonary disease (COPD), and in critical illness. Although mouse
      studies indicate causative associations between adiponectin and asthma and COPD,
      the human literature in this regard is inconclusive. Some, but not all, studies
      demonstrate that serum adiponectin concentrations are inversely associated with
      asthma prevalence among premenopausal women and peripubertal girls. On the other
      hand, serum adiponectin concentrations are associated with lower asthma severity
      among boys but greater severity among men. Further, case-control studies
      demonstrate higher systemic and airway adiponectin concentrations in primarily
      male COPD patients than controls. Systemic adiponectin is positively associated
      with lung function in healthy adults but inversely associated in studies of male
      subjects with COPD. Murine and human studies further show contradictory
      associations of systemic adiponectin with critical illness. Higher premorbid
      systemic adiponectin concentrations are associated with improved survival from
      sepsis in mice. On the other hand, higher systemic adiponectin concentrations on
      day 1 of critical illness are associated with lower survival in critically ill
      patients with respiratory failure. In the absence of adequate longitudinal data,
      it is not possible to determine whether the adiponectin derangements are the
      consequence or the cause of the disease studied. Future research will determine
      whether modulation of adiponectin, independent of BMI, may be helpful in the
      prevention or treatment of asthma, COPD or critical illness.

PMID- 22876928
TI  - Adiponectin, an anti-carcinogenic hormone? A systematic review on breast,
      colorectal, liver and prostate cancer.
AB  - Adiponectin is an adipose tissue-derived hormone, expressed almost exclusively in
      adipose tissue, with significant antidiabetic, anti-atherosclerotic, anti
      inflammatory and anti-proliferative properties. The anti-carcinogenic effects of
      adiponectin result from two main mechanisms: a modulation in the signaling
      pathways involved in proliferation process and a subtle regulation of the
      apoptotic response. In this review, we present recent findings on the association
      of adiponectin with the risk of several malignancies (breast, colorectal, liver
      and prostate cancers), as well as data on underlying molecular mechanisms by
      which adiponectin plays a substantial role in cancer pathogenesis.

PMID- 22876929
TI  - Photochemistry of a bacterial photosynthetic reaction center missing the initial
      bacteriochlorophyll electron acceptor.
AB  - A novel chromophore composition of the bacterial photosynthetic reaction center
      (RC) has been discovered: RCs lacking the L-side monomeric bacteriochlorophyll
      chromophore result from mutation of the native isoleucine at M204 to glutamine in
      Rhodobacter capsulatus . This conclusion is obtained from 77 K UV-vis
      spectroscopy and pigment extractions of the I(M204)Q mutant and seven variants
      containing the I(M204)Q plus other mutations. The oxidation potential of the
      primary electron donor P (a dimer of bacteriochlorophylls) was measured for three
      of the mutants and found to be 50-65 mV lower than in wild-type RCs. Ultrafast
      transient absorption measurements reveal (minimally) two subpopulations of P*
      that have distinct lifetimes and photochemical outcomes for all mutants
      containing I(M204)Q. In one subpopulation P* decays solely by internal conversion
      to the ground state. In the other subpopulation P* decays by electron transfer to
      the normally inactive M-side bacteriopheophytin (H(M)) in competition with
      internal conversion to the ground state. When a Tyr residue is substituted for
      the native Phe at L181 near the M-side monomeric bacteriochlorophyll (B(M)), the
      rate of electron transfer to H(M) is increased about 4-fold.

PMID- 22876930
TI  - Simultaneous gauche and anomeric effects in alpha-substituted sulfoxides.
AB  - alpha-Substituted sulfoxides can experience both gauche and anomeric effects,
      since these compounds have the geometric requirements and strong electron donor
      and acceptor orbitals which are essential to make operative the hyperconjugative
      nature of these effects. Indeed, the title effects were calculated to take place
      for 1,3-oxathiane 3-oxide in polar solution, where dipolar effects are absent or
      at least minimized, while only the gauche effect is present in 2-fluorothiane 1
      oxide. Since the fluorine atom is a suitable probe for structural analysis using
      NMR, the (1)J(CF) dependence on the rotation around the F-C-S?O dihedral angle of
      (fluoromethyl)methyl sulfoxide was evaluated; differently from 1,2-difluoroethane
      and fluoro(methoxy)methane, this coupling constant is at least not exclusively
      dependent on dipolar interactions (or on hyperconjugation). Because of the
      nonmonotonic behavior of the (1)J(CF) rotational profile, this coupling constant
      does not appear to be of significant diagnostic value for probing the
      conformations of alpha-fluoro sulfoxides.

PMID- 22876932
TI  - Tuning the activity of platinum(IV) anticancer complexes through asymmetric
      acylation.
AB  - Platinum(II) anticancer drug cisplatin is one of the most important
      chemotherapeutic agents in clinical use but is limited by its high toxicity and
      severe side effects. Platinum(IV) anticancer prodrugs can overcome these
      limitations by resisting premature aquation and binding to essential plasma
      proteins. Structure-activity relationship studies revealed a link between the
      efficacy of platinum(IV) complexes with the nature of their axial ligands, which
      can be modified to enhance the properties of the prodrug. The existing paradigm
      of employing platinum(IV) complexes with symmetrical axial carboxylate ligands
      does not fully exploit their vast potential. A new approach was conceived to
      control properties of platinum(IV) prodrugs using contrasting axial ligands via
      sequential acylation. We report a novel class of asymmetric platinum(IV)
      carboxylates based on the cisplatin template containing both hydrophilic and
      lipophilic ligands on the same scaffold designed to improve their aqueous
      properties and enhance their efficacy against cancer cells in vitro.

PMID- 22876931
TI  - Comparison of the efficacy of intravitreal triamcinolone acetonide for cystoid
      macular edema with versus without serous retinal detachment in branch retinal
      vein occlusion: influence on macular sensitivity and morphology.
AB  - BACKGROUND: The influence of serous retinal detachment (SRD) on visual acuity,
      macular sensitivity, and macular thickness is unclear after intravitreal
      injection of triamcinolone acetonide (IVTA) for macular edema with branch retinal
      vein occlusion (BRVO). METHODS: Twenty-one eyes of 21 BRVO patients with macular
      edema received IVTA. Patients were divided into two groups by optical coherence
      tomography findings: 11 patients who had cystoid macular edema (CME) with SRD
      (SRD (+) group) and 10 patients who had CME without SRD (SRD (-) group).
      Microperimetry was performed with a Micro Perimeter 1 before and at 3 and 6
      months after IVTA. Macular thickness was measured by optical coherence
      tomography. We exchanged the superior and inferior regions to separate the
      regions into those with and without occlusion. As a result, the superior region
      was always the occluded region and the inferior region was non-occluded. RESULTS:
      In both the SRD (-) group and the SRD (+) group, the mean macular thickness
      within the central 4 degrees  field and the 10 degrees  and 20 degrees  fields of
      the occluded region decreased significantly from baseline to 3 and 6 months after
      IVTA (all P <0.01). Visual acuity also improved significantly in both groups from
      baseline to 3 and 6 months after IVTA (both P <0.05). In both groups, the mean
      macular sensitivity (measured with by microperimetry) within the central 4
      degrees  field and the 10 degrees  and 20 degrees  fields of the occluded region
      showed a significant increase from baseline to 3 and 6 months after IVTA (all P
      <0.05). The trend profiles of macular thickness within the 10 degrees  and 20
      degrees  fields of the occluded region showed significant differences, but there
      were no significant differences with respect to the trend profiles of visual
      acuity and macular sensitivity within the central 4 degrees  field and the 10
      degrees  and 20 degrees  fields of the occluded region. CONCLUSIONS: These
      results suggest that IVTA may achieve more marked improvement of macular
      morphology in BRVO patients with SRD than in those without SRD, while this
      therapy may have a similar effect on macular function in BRVO patients with or
      without SRD.

PMID- 22876933
TI  - Comparison of the quality of basic life support provided by rescuers trained
      using the 2005 or 2010 ERC guidelines.
AB  - INTRODUCTION: Effective delivery of cardiopulmonary resuscitation (CPR) and
      prompt defibrillation following sudden cardiac arrest (SCA) is vital. Updated
      guidelines for adult basic life support (BLS) were published in 2010 by the
      European Resuscitation Council (ERC) in an effort to improve survival following
      SCA. There has been little assessment of the ability of rescuers to meet the
      standards outlined within these new guidelines. METHODS: We conducted a
      retrospective analysis of the performance of first year healthcare students
      trained and assessed using either the new 2010 ERC guidelines or their 2005
      predecessor, within the University of Birmingham, United Kingdom. All students
      were trained as lay rescuers during a standardised eight hour ERC-accredited
      adult BLS course. RESULTS: We analysed the examination records of 1091 students.
      Of these, 561 were trained and assessed using the old 2005 ERC guidelines and 530
      using the new 2010 guidelines. A significantly greater proportion of candidates
      failed in the new guideline group (16.04% vs. 11.05%; p < 0.05), reflecting a
      significantly greater proportion of lay-rescuers performing chest compressions at
      too fast a rate when trained and assessed with the 2010 rather than 2005
      guidelines (6.04% vs. 2.67%; p < 0.05). Error rates for other skills did not
      differ between guideline groups. CONCLUSIONS: The new ERC guidelines lead to a
      greater proportion of lay rescuers performing chest compressions at an
      erroneously fast rate and may therefore worsen BLS efficacy. Additional study is
      required in order to define the clinical impact of compressions performed to a
      greater depth and at too fast a rate.

PMID- 22876934
TI  - Wireless distributed functional electrical stimulation system.
AB  - BACKGROUND: The control of movement in humans is hierarchical and distributed and
      uses feedback. An assistive system could be best integrated into the therapy of a
      human with a central nervous system lesion if the system is controlled in a
      similar manner. Here, we present a novel wireless architecture and routing
      protocol for a distributed functional electrical stimulation system that enables
      control of movement. METHODS: The new system comprises a set of miniature battery
      powered devices with stimulating and sensing functionality mounted on the body of
      the subject. The devices communicate wirelessly with one coordinator device,
      which is connected to a host computer. The control algorithm runs on the computer
      in open- or closed-loop form. A prototype of the system was designed using
      commercial, off-the-shelf components. The propagation characteristics of
      electromagnetic waves and the distributed nature of the system were considered
      during the development of a two-hop routing protocol, which was implemented in
      the prototype's software. RESULTS: The outcomes of this research include a novel
      system architecture and routing protocol and a functional prototype based on
      commercial, off-the-shelf components. A proof-of-concept study was performed on a
      hemiplegic subject with paresis of the right arm. The subject was tasked with
      generating a fully functional palmar grasp (closing of the fingers). One node was
      used to provide this movement, while a second node controlled the activation of
      extensor muscles to eliminate undesired wrist flexion. The system was tested with
      the open- and closed-loop control algorithms. CONCLUSIONS: The system fulfilled
      technical and application requirements. The novel communication protocol enabled
      reliable real-time use of the system in both closed- and open-loop forms. The
      testing on a patient showed that the multi-node system could operate effectively
      to generate functional movement.

PMID- 22876935
TI  - Timing of elective repeated cesarean delivery in patients with previous two or
      more cesarean section.
AB  - OBJECTIVE: To assess the maternal and neonatal consequences of scheduling
      elective repeated cesarean section (ERCS) at 39 weeks rather than 38 weeks and to
      assess the impacts of delivering by emergency cesarean section (CS) before the
      planned date. DESIGN: Retrospective Cohort study. POPULATION: Patients with
      previous two or more CS planned for ERCS at term during the period from January
      to June 2011. METHODS: Medical records were reviewed for demographic and clinical
      data, planned timing of CS, emergency cesarean and any adverse maternal or
      neonatal outcome. MAIN OUTCOME MEASURES: Adverse maternal or neonatal outcome.
      RESULTS: Four hundred and twenty women were included, 71.4% of cases were posted
      <39 weeks and 28.6% were posted at >=39 weeks. Patients posted >= 39 weeks were
      more prone to deliver by emergency CS (16.6 vs. 10.6%) and the neonates were less
      prone to RDS and NICU admission (p < 0.05). CONCLUSION: Our data support the
      justification to book patients for ERCS at >=39 weeks.

PMID- 22876936
TI  - The item level psychometrics of the behaviour rating inventory of executive
      function-adult (BRIEF-A) in a TBI sample.
AB  - PRIMARY OBJECTIVE: To determine whether the psychometrics of the BRIEF-A are
      adequate for individuals diagnosed with TBI. RESEARCH DESIGN: A prospective
      observational study in which the BRIEF-A was collected as part of a larger study.
      METHODS AND PROCEDURES: Informant ratings of the 75-item BRIEF-A on 89
      individuals diagnosed with TBI were examined to determine items level
      psychometrics for each of the two BRIEF-A indexes: Behaviour Rating Index (BRI)
      and Metacognitive Index (MI). Patients were either outpatients or at least 1 year
      post-injury. MAIN OUTCOMES AND RESULTS: Each index measured a latent trait,
      separating individuals into five-to-six ability levels and demonstrated good
      reliability (0.94 and 0.96). Four items were identified that did not meet the
      infit criteria. CONCLUSIONS: The results provide support for the use of the BRIEF
      A as a supplemental assessment of executive function in TBI populations. However,
      further validation is needed with other measures of executive function.
      Recommendations include use of the index scores over the Global Executive
      Composite score and use of the difficulty hierarchy for setting therapy goals.

PMID- 22876938
TI  - Dynamic equilibria in an epidemic model with voluntary vaccinations.
AB  - The dynamics of an epidemic model with voluntary vaccinations are studied.
      Individual vaccination decisions are modelled using an economic/game-theoretic
      approach: agents in the model decide whether to vaccinate or not by weighing the
      cost and benefit of vaccination and choose the action that maximizes their net
      benefit. It is shown that, when vaccine efficacy is low, there are parameter
      values for which multiple steady-state equilibria and periodic equilibria
      coexist. When multiplicity of steady states is obtained, which one the population
      reaches in some cases depends entirely on agents' expectations concerning the
      future course of an epidemic and not on the initial conditions of the model.   
      (?)Comments and suggestions from anonymous referees of the journal are gratefully
      acknowledged. This paper is dedicated to the loving memory of Lucy Hauser.

PMID- 22876939
TI  - The relationship between endophyte transition and plant species coexistence.
AB  - The survival possibilities of terrestrial plant species are determined by their
      competitive abilities. One factor that affects competitive ability is the
      community of microorganisms that lives in association with the plants.
      Microorganisms affect the competitive dominance among plants by means of their
      metabolites. In this paper, we study the multiple plant species coexistence
      mediated by interactions with endophytes (fungi). The population dynamics are
      described by a revised lottery competition model for multiple plant species, each
      of which is divided into two classes: plants with endophytes (denoted EP) and
      plants without endophytes (NEP). The model includes the transition of seeds from
      EP to NEP. We show multiple species of plants cannot coexist in a steady state if
      this transition is density independent, but can coexist in a steady state if this
      transition is an increasing function of population density.

PMID- 22876940
TI  - Dynamics of an HIV-1 therapy model of fighting a virus with another virus.
AB  - In this paper, we rigorously analyse an ordinary differential equation system
      that models fighting the HIV-1 virus with a genetically modified virus. We show
      that when the basic reproduction ratio R(0)<1, then the infection-free
      equilibrium E (0) is globally asymptotically stable; when R(0)>1, E (0) loses its
      stability and there is the single-infection equilibrium E (s). If R(0)?(1,
      1+delta) where delta is a positive constant explicitly depending on system
      parameters, then the single-infection equilibrium E (s) that is globally
      asymptotically stable, while when R(0)>1+delta, E (s) becomes unstable and the
      double-infection equilibrium E (d) comes into existence. When R(0) is slightly
      larger than 1+delta, E (d) is stable and it loses its stability via Hopf
      bifurcation when R(0) is further increased in some ways. Through a numerical
      example and by applying a normal form theory, we demonstrate how to determine the
      bifurcation direction and stability, as well as the estimates of the amplitudes
      and the periods of the bifurcated periodic solutions. We also perform numerical
      simulations which agree with the theoretical results. The approaches we use here
      are a combination of analysis of characteristic equations, fluctuation lemma,
      Lyapunov function and normal form theory.

PMID- 22876937
TI  - Implantation of undifferentiated and pre-differentiated human neural stem cells
      in the R6/2 transgenic mouse model of Huntington's disease.
AB  - BACKGROUND: Cell therapy is a potential therapeutic approach for several
      neurodegenetative disease, including Huntington Disease (HD). To evaluate the
      putative efficacy of cell therapy in HD, most studies have used excitotoxic
      animal models with only a few studies having been conducted in genetic animal
      models. Genetically modified animals should provide a more accurate
      representation of human HD, as they emulate the genetic basis of its etiology.
      RESULTS: In this study, we aimed to assess the therapeutic potential of a human
      striatal neural stem cell line (STROC05) implanted in the R6/2 transgenic mouse
      model of HD. As DARPP-32 GABAergic output neurons are predominately lost in HD,
      STROC05 cells were also pre-differentiated using purmorphamine, a hedgehog
      agonist, to yield a greater number of DARPP-32 cells. A bilateral injection of
      4.5x105 cells of either undifferentiated or pre-differentiated DARPP-32 cells,
      however, did not affect outcome compared to a vehicle control injection. Both
      survival and neuronal differentiation remained poor with a mean of only 161 and
      81 cells surviving in the undifferentiated and differentiated conditions
      respectively. Only a few cells expressed the neuronal marker Fox3. CONCLUSIONS:
      Although the rapid brain atrophy and short life-span of the R6/2 model constitute
      adverse conditions to detect potentially delayed treatment effects, significant
      technical hurdles, such as poor cell survival and differentiation, were also sub
      optimal. Further consideration of these aspects is therefore needed in more
      enduring transgenic HD models to provide a definite assessment of this cell
      line's therapeutic relevance. However, a combination of treatments is likely
      needed to affect outcome in transgenic models of HD.

PMID- 22876941
TI  - Evolution of cross-diffusion and self-diffusion.
AB  - This article is concerned with the evolution of certain types of density
      dependent dispersal strategy in the context of two competing species with
      identical population dynamics and same random dispersal rates. Such density
      dependent movement, often referred to as cross-diffusion and self-diffusion,
      assumes that the movement rate of each species depends on the density of both
      species and that the transition probability from one place to its neighbourhood
      depends solely on the arrival spot (independent of the departure spot). Our
      results suggest that for a one-dimensional homogeneous habitat, if the gradients
      of two cross- and self-diffusion coefficients have the same direction, the
      species with the smaller gradient will win, i.e. the dispersal strategy with the
      smaller gradient of cross- and self-diffusion coefficient will evolve. In
      particular, it suggests that the species with constant cross- and self-diffusion
      coefficients may have competitive advantage over species with non-constant cross-
      and self-diffusion coefficients. However, if the two gradients have opposite
      directions, neither of the two dispersal strategies wins as these two species can
      coexist.

PMID- 22876942
TI  - Malaria model with periodic mosquito birth and death rates.
AB  - In this paper, we introduce a model of malaria, a disease that involves a complex
      life cycle of parasites, requiring both human and mosquito hosts. The novelty of
      the model is the introduction of periodic coefficients into the system of one
      dimensional equations, which account for the seasonal variations (wet and dry
      seasons) in the mosquito birth and death rates. We define a basic reproduction
      number R(0) that depends on the periodic coefficients and prove that if R(0)<1
      then the disease becomes extinct, whereas if R(0)>1 then the disease is endemic
      and may even be periodic.

PMID- 22876943
TI  - Anti-inflammatory trends of 1, 3-diphenyl-2-propen-1-one derivatives.
AB  - Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon alpha,
      beta-unsaturated carbonyl system. The biosynthesis of flavonoids and
      isoflavonoids is initiated by chalcones. Notable pharmacological activities of
      chalcones and its derivatives include anti-inflammatory, antifungal,
      antibacterial, antimalarial, antituberculosis, antitumor, antimicrobial and
      antiviral effects respectively. Owing to simplicity of the chemical structures
      and a huge variety of pharmacological actions exhibited, the entities derived
      from chalcones are subjected to extensive consideration. This review article is
      an effort to sum up the anti-inflammatory activities of chalcone derived chemical
      entities. Effect of chalcones on lipid peroxidation, heme oxygenase 1(HO-1),
      cyclooxygenase (COX), interleukin 5 (IL-5), nitric oxide (NO) and expression of
      cell adhesion molecules (CAM) is summarized stepwise.

PMID- 22876944
TI  - Anti-cancer targeting telomerase inhibitors: beta-rubromycin and oleic acid.
AB  - Telomerase is a ribonucleoprotein complex that elongates telomeric DNA and
      appears to play an important part in the cellular immortalization of cancers. In
      the screening of potent inhibitors of human telomerase, several inhibitors have
      been discovered from natural and chemical sources. Some compounds potently
      inhibit the activity of human telomerase. Rubromycins and fatty acids such as
      beta-rubromycin and oleic acid, respectively, were found to be inhibitors of
      human telomerase. The IC(50) values of beta-rubromycin and oleic acid were 8.60
      and 8.78 MUM, respectively. A kinetic study revealed that these compounds
      competitively inhibited the activity of telomerase with respect to the substrate
      of the primer and dNTP. The energy-minimized three-dimensional structure of beta
      rubromycin and oleic acid was calculated and designed. The V-shaped curve and
      molecule length of 18.7-20.3 A in these compound structures were suggested to be
      important for telomerase inhibition. The three-dimensional structure of the
      active site of telomerase (i.e., the binding site of the primer and dNTP
      substrate) might have a "pocket" that could "join" these compounds. These results
      appear to suggest a potential structure for the development of more potent
      inhibitors of human telomerase.

PMID- 22876945
TI  - Non-monoaminergic targets for the development of antidepressants: focus on
      neuropeptides.
AB  - In the last decades, no significant paradigm shifts in the psychopharmacology of
      major depressive disorder (MDD) have occurred. In fact, after the serendipitous
      discovery of the first antidepressant, the poor understanding of the
      pathophysiology of the illness has deeply limited the development of novel
      antidepressant agents. Although the discovery of the selective serotonin reuptake
      inhibitors and the dual-acting serotonin/norepinephrine reuptake inhibitors
      allowed to improve the treatment of MDD, there are still important unmet clinical
      needs, as the long latency of antidepressant action, the presence of relevant
      side effects and the lack of efficacy. In fact, even though the available
      antidepressants have consistently improved the prognosis of the disorder, the
      pharmacological treatment of MDD is far from being satisfactory and the disorder
      remains one of the major causes of morbidity and disability worldwide. Recently,
      besides the classical research involving the monoamines, other non-monoaminergic
      molecular mechanisms have been explored in search of new antidepressants. Amongst
      them, the investigation of the central neuropeptides, including substance P,
      corticotropin-releasing factor, neuropeptide Y, vasopressin and oxytocin, galanin
      and melanin-concentrating hormone, is increasingly attracting the attention of
      researchers worldwide. A number of novel compounds acting on neuropeptide
      receptors have been developed and tested in both animals and humans with
      different results. In this review, we provided a synthetic overview of the main
      neuropeptides, going through biochemical and molecular aspects up to preclinical
      and clinical evidence which link these molecules to the presence of MDD.

PMID- 22876946
TI  - Synthesis and biological activity of 3-N-substituted estrogen derivatives as
      breast cancer agents.
AB  - 3-N-substituted-estrogen derivatives were synthesized and characterized. Their
      antiproliferative activities against human ER (+) MCF-7 (Breast), ER (-) MDA-MB
      231 (breast) and Ishikawa (endometrial) cancer cell lines were determined after
      72 hours drug exposure employing CellTiter-Glo assay at concentrations ranging
      from (0.01-100,000 nM). The antiproliferative activities of these compounds were
      compared to tamoxifen (TAM), 4-hydroxytamoxifen (4-OHT, active metabolite of
      tamoxifen) and raloxifene (RAL). In vitro results indicated that compound 5 (IC50
      = 12 uM) displayed comparable antiproliferative activity against MDA-MB 231 cell
      line; while compounds 6, 7 and 13 (IC50 = 12 uM) displayed higher activity
      against MCF-7 and Ishikawa cell lines, in comparison to TAM activity (19-33 uM).

PMID- 22876947
TI  - Piperidin-4-one: the potential pharmacophore.
AB  - The piperidin-4-ones have been reported as versatile intermediates. They have
      been synthesized using a variety of methods, including Mannich reaction and
      stereoselective synthesis. The piperidin-4-ones have been reported to possess
      various pharmacological activities, including anticancer and anti HIV activities.
      The pharmacophore can be suitably modified in order to achieve better receptor
      interactions and biological activities. The renewed interest in the nucleus has
      re-established the importance of piperidin-4-ones in medicinal chemistry. The
      review intends to discuss the current research trends in the synthetic protocols,
      characterization, stereochemistry and important biological activities of
      piperidin-4-ones during the last decade.

PMID- 22876948
TI  - Synthesis and anti-inflammatory effects of new piperazine and ethanolamine
      derivatives of H(1)-antihistaminic drugs.
AB  - In addition to their antihistamine effects, H1-receptor antagonists possess
      pharmacological properties that are not uniformly distributed among this class of
      drugs, such as anti-inflammatory, anti-allergic and antiplatelet activities. In
      this paper, Cyclizine (1-benzhydryl-4-methyl-piperazine, I), bromodiphenhydramine
      (2-[(4-bromophenyl)-phenylmethoxy]-N, N-dimethylethanamine, II) and some of their
      new piperazine and ethanolamine derivatives (III-VIII) inducing changes in
      substitution of phenyl and amine moieties were synthesized and their acute and
      chronic antiinflammatory effects were evaluated by standard pharmacological
      tests. The results showed that substitution of phenyl by tolyl, anisol and cumene
      groups in piperazine family could remarkably decrease acute inflammation in these
      new drugs. Also, substitution of dimethylamine by morpholine group could not
      decrease this inflammation in new synthesized ethanolamine family. But the
      results from the cotton pellet-induced granuloma formation in rats showed that
      none of drugs (I-VIII) were effective to reduce the chronic inflammation.

PMID- 22876949
TI  - Chalcones in cancer: understanding their role in terms of QSAR. II part.
AB  - Chalcones are a group of plant-derived polyphenolic compounds belonging to the
      flavonoids family and possess a wide variety of cytoprotective and modulatory
      functions. In this research we tried to review the anticancer effect of chalcones
      derivatives and to evaluate new QSARs which will help in the understanding of the
      role of chalcones and of their analogs on cancer. Simultaneously a comparative
      study will be presented. Our QSAR results reveal that: 1) the clog P
      (hydrophobicity/hydrophilicity) parameter plays an important part in three QSAR
      relationships (linear model), 2) the steric factors such as molar volume MgVol,
      molar refractivity CMR or the substituents molar refractivity MR (linear) are
      important. Electronic effects are comparatively unimportant. These results
      compared to our previous findings on the QSAR of anti-proliferative chalcones
      support primarily the role of bulk.

PMID- 22876950
TI  - Snake venom induced local toxicities: plant secondary metabolites as an auxiliary
      therapy.
AB  - Snakebite is a serious medical and socio-economic problem affecting the rural and
      agricultural laborers of tropical and sub-tropical region across the world
      leading to high morbidity and mortality. In most of the snakebite incidences,
      victims usually end up with permanent tissue damage and sequelae with high
      socioeconomic and psychological impacts. Although, mortality has been reduced
      markedly due to anti-venom regimen, it is associated with several limitations.
      Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the
      kingpins of tissue necrosis and extracellular matrix degradation. Thus,
      inhibition of these enzymes is considered to be the rate limiting step in the
      management of snakebite. Unfortunately, tissue necrosis and extracellular matrix
      degradation persists even after the administration of anti-venom. At present,
      inhibitors from snake serum and plasma, several synthetic compounds and their
      analogs have been demonstrated to possess anti-snake venom activities, but the
      use of plant metabolites for this purpose has an added advantage of traditional
      knowledge and will make the treatment cheaper and more accessible to the affected
      population. Therefore, the clinical and research forums are highly oriented
      towards plant metabolites and interestingly, certain phytochemicals are
      implicated as the antibody elicitors against venom toxicity that can be exploited
      in designing effective anti-venoms. Based on these facts, we have made an effort
      to enlist plant based secondary metabolites with antiophidian abilities and their
      mechanism of action against locally acting enzymes/toxins in particular. The
      review also describes their functional groups responsible for therapeutic
      beneficial and certainly oblige in designing potent inhibitors against venom
      toxins.

PMID- 22876951
TI  - Histone deacetylases as targets for multiple diseases.
AB  - Inhibition of Histone deacetylases (HDACs) has been emerged as important approach
      to reverse aberrant epigenetic changes associated with various cancerous and non
      cancerous diseases. The field of histone deacetylase inhibitors (HDIs) is moving
      into a new phase of development. The structure of histone deacetylases is well
      established and the active sites have been well identified. Various drugs
      targeting this enzyme are in the pipeline for the treatment of different
      diseases. Since first-generation HDAC inhibitors proved their clinical
      fruitfulness and also second generation inhibitors are rationally designed with
      improved specificity, experts believe that this class will emerge in the
      treatment of various diseases. Considering these facts present review focuses on
      HDACs and developments of HDIs in the treatment of various diseases.

PMID- 22876952
TI  - Bioactive natural compounds from the plant endophytic fungi Pestalotiopsis spp.
AB  - The plant-endophytic strains of the fungus Pestalotiopsis (Amphisphaeriaceae) are
      distributed throughout the world. Previous chemical investigation of members of
      the genus resulted in the discovery of various bioactive secondary metabolites
      including chromones, cytosporones, polyketides, terpenoids and coumarins with
      diverse structural features. The present report reviews the papers, which have
      appeared in the literature till now, concerning the isolation, structural
      elucidation, and biological activities of the secondary metabolites from
      Pestalotiopsis species.

PMID- 22876953
TI  - Mechanism-based modulator discovery for sirtuin-catalyzed deacetylation reaction.
AB  - Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of
      evolutionarily conserved intracellular protein deacetylases that can catalyze the
      acetyl group removal from the specific Nepsilon-acetyl-lysine (AcK) side chains
      on a variety of proteins from all kingdoms of life. Yeast Sir2 was the first
      sirtuin identified, and so far seven sirtuins (i.e. SIRT1-7) have been found in
      mammals including humans. The sirtuin-catalyzed deacetylation reaction has
      captured tremendous interest during the past a few years because of (i) its
      increasingly demonstrated importance in many crucial biological processes such as
      gene transcription, metabolism, and aging, and thus its therapeutic potential for
      metabolic and age-related diseases and cancer, and (ii) its unique deacetylation
      chemistry. Specifically, the sirtuin-catalyzed AcK side chain deacetylation is
      not merely an amide hydrolysis reaction, instead is coupled to the nicotinamide
      cleavage from beta-nicotinamide adenine dinucleotide (beta-NAD+ or NAD+) with the
      generation of three enzymatic products, i.e. the deacetylated protein species,
      nicotinamide, and 2'-O-acetyl-ADP-ribose (2'-O-AADPR). Here the author would like
      to review the past endeavors on developing mechanism-based sirtuin modulators
      (inhibitors and activators). The first part of this article will provide an
      updated mechanistic picture of the sirtuin-catalyzed deacetylation reaction. The
      second part will be focused on how the mechanistic knowledge has been exploited
      for the design of effective sirtuin modulators.

PMID- 22876954
TI  - Somatostatin and cognitive function in neurodegenerative disorders.
AB  - During the past 40 years, somatostatin (SST) has been a subject of intensive
      research. Apart from its substantial role in the neuroendocrine system, due to
      its dense localization in various areas in the brain, its functions as a
      neuromodulator have also been thoroughly investigated. Increasing evidence
      suggests that SST plays a crucial role in memory and cognition. Synthetic forms,
      biologically active peptide sequences, SST receptor agonists and SST depleting
      agents have been applied in animal models and in human studies of a number of
      neuropsychiatric disorders. The translation of experimental data into clinical
      use could provide novel therapies in neurodegenerative disorders involving
      cognitive dysfunctions. However in view of the controversial data reported
      concerning the different roles of the SST receptor subtypes, and the lack of SST
      analogs that are able to cross diffusion barriers and act selectively at these
      receptor subtypes, broader clinical use of SST analogs as cognitive enhancers is
      limited. This review covers the whole range of available experimental results
      relating to the behavioral effects of SST, and highlights the potential for
      further investigations.

PMID- 22876955
TI  - Potential triazole derivatives having significant antiepileptic effect- A Review.
AB  - Triazole is a five membered heterocyclic moiety of two carbon and three nitrogen
      atom, triazole are present in two isomeric forms, 1,2,4-triazole and 1,2,3
      triazole. Alprazolam, Triazolam and Midazolam are established drugs used in
      epilepsy which have triazole moiety. Epilepsy is the most frequent neurological
      disorder characterized by excessive temporary neuronal discharge. The overall
      prevalence of the disease is 1% of the population and up to 50 million people
      worldwide. The literature shows that different substitution on triazole moiety
      exhibit potent antiepileptic activity and less/no neurotoxicity. The maximal
      electroshock seziures test is most widely used in- vivo models among the various
      screening models of epilepsy. The present article focused on the previous
      researches on triazole, which include synthesis, spectral characterization and
      antiepileptic activity of the synthesized triazole derivatives, and we also go
      for the development of structure activity relationship of the earlier synthesized
      triazole derivatives with reference to their pharmacological effect.

PMID- 22876956
TI  - Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs
      used as modulators of the nitroxidative stress.
AB  - Numerous lines of evidence suggest that heterocyclic compounds used as analgesic,
      anti-inflammatory and anti-migraine agents can be potent regulators of the
      nitroxidative stress and targeting free nitrogen and oxygen radicals is a very
      promising strategy for future pain management. Both classical analgesics
      (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic
      adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine,
      escitalopram, phenytoin or carbamazepine and alpha-lipoic acid can modulate the
      balance between pro-oxidant and antioxidant processes in the mammalian tissues
      and these properties of drugs such as indomethacin, meloxicam, tenoxicam,
      valdecoxib or some metabolites of analgesic drugs formed by the activity of
      tissue peroxidases may contribute to their clinical efficacy and drug-related
      toxic effects, including gastrointestinal ulcers, hepatic failure,
      agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and
      tolerance. The antioxidant capacities of novel heterocyclic compounds, including
      the compounds acting either by prevention of formation or catalyzed decomposition
      of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts
      or as superoxide (O2 *-)-scavengers which are the functional mimetics of
      superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro
      3,4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or gamma-butyrolactone
      (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and
      promising future heterocyclic analgesics.

PMID- 22876957
TI  - The antioxidant activity of coumarins and flavonoids.
AB  - Coumarins and flavonoids are heterocyclic molecules that have been associated
      with beneficial effects on human health, such as reducing the risk of cancer,
      diabetes, cardiovascular and brain diseases. These effects are thought to be
      related to the radical scavenging effect, due to their antioxidant activities,
      along with other possible mechanisms, such as anti-inflammatory properties and
      interaction with several enzymes. Over the past two decades, there have been an
      increasing number of publications on coumarins and flavonoids, which demonstrate
      the importance of understanding the chemistry behind the antioxidant activities
      of both natural and synthesized compounds, considering the benefits from their
      dietary ingestion as well as pharmacological use. This work aims to review the
      antioxidant effects of coumarin and flavonoid molecules in humans and the
      structural aspects that contribute to these effects.

PMID- 22876958
TI  - Synthesis and biological evaluation of chalcone derivatives (mini review).
AB  - Chalcones are the principal precursors for the biosynthesis of flavonoids and
      isoflavonoids. A three carbon alpha, beta-unsaturated carbonyl system constitutes
      chalcones. Chalcones are the condensation products of aromatic aldehyde with
      acetophenones in attendance of catalyst. They go through an assortment of
      chemical reactions and are found advantageous in synthesis of pyrazoline,
      isoxazole and a variety of heterocyclic compounds. In synthesizing a range of
      therapeutic compounds, chalcones impart key role. They have showed worth
      mentioning therapeutic efficacy for the treatment of various diseases. Chalcone
      based derivatives have gained heed since they own simple structures, and diverse
      pharmacological actions. A lot of methods and schemes have been reported for the
      synthesis of these compounds. Amongst all, Aldol condensation and Claisen-Schmidt
      condensation still grasp high up position. Other distinguished techniques include
      Suzuki reaction, Witting reaction, Friedel-Crafts acylation with cinnamoyl
      chloride, Photo-Fries rearrangement of phenyl cinnamates etc. These inventive
      techniques utilize various catalysts and reagents including SOCl(2) natural
      phosphate, lithium nitrate, amino grafted zeolites, zinc oxide, water,
      Na(2)CO(3), PEG400, silicasulfuric acid, ZrCl(4) and ionic liquid etc. The
      development of better techniques for the synthesis of alpha, beta- unsaturated
      carbonyl compounds is still in high demand. In brief, we have explained the
      methods and catalysts used in the synthesis of chalcones along with their
      biological activities in a review form to provide information for the development
      of new-fangled processes targeting better yield, less reaction time and least
      side effects with utmost pharmacological properties.

PMID- 22876959
TI  - Optimized methods for in vitro and in vivo anti-inflammatory assays and its
      applications in herbal and synthetic drug analysis.
AB  - Inflammatory diseases including, different types of rheumatic diseases are the
      major problems associated with the presently available non-steroidal anti
      inflammatory agents. The numbers of plant derived drugs have been screened for
      their anti-inflammatory and anti-arthritic activity. Drug development in the
      recent times often relies on use of natural and synthetic drugs, which are
      promising candidates as therapeutic agents for prevention of diseases and
      disorders. These drugs possess different chemical structures, with wide range of
      therapeutic activities. The mechanism of Inflammation mainly involve in
      development of serious diseases, such as cancer, rheumatoid arthritis, sprains,
      bronchitis, muscle pains, chronic inflammatory bowel disease, persistent asthma,
      and liver fibrosis. Development of inflammatory events basically related to
      various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF);
      endogenous factors such as tumor necrosis factor alpha (TNF-alpha); enzymes and
      proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory
      peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon
      gamma (IFN-gamma), COX, LOX, cytokines such as interleukin-1 (IL-1); reactive
      oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as pro
      inflammatory cells such as T and NK cells are well known to have an important
      role. Based on these correlations, numerous assays were used for inflammatory
      mechanism research, which was described in this paper.

PMID- 22876960
TI  - A draft genome sequence of Nicotiana benthamiana to enhance molecular plant
      microbe biology research.
AB  - Nicotiana benthamiana is a widely used model plant species for the study of
      fundamental questions in molecular plant-microbe interactions and other areas of
      plant biology. This popularity derives from its well-characterized susceptibility
      to diverse pathogens and, especially, its amenability to virus-induced gene
      silencing and transient protein expression methods. Here, we report the
      generation of a 63-fold coverage draft genome sequence of N. benthamiana and its
      availability on the Sol Genomics Network for both BLAST searches and for
      downloading to local servers. The estimated genome size of N. benthamiana is 3 Gb
      (gigabases). The current assembly consists of approximately 141,000 scaffolds,
      spanning 2.6 Gb with 50% of the genome sequence contained within scaffolds >89
      kilobases. Of the approximately 16,000 N. benthamiana unigenes available in
      GenBank, >90% are represented in the assembly. The usefulness of the sequence was
      demonstrated by the retrieval of N. benthamiana orthologs for 24 immunity
      associated genes from other species including Ago2, Ago7, Bak1, Bik1, Crt1, Fls2,
      Pto, Prf, Rar1, and mitogen-activated protein kinases. The sequence will also be
      useful for comparative genomics in the Solanaceae family as shown here by the
      discovery of microsynteny between N. benthamiana and tomato in the region
      encompassing the Pto and Prf genes.

PMID- 22876961
TI  - Arabidopsis clade I TGA transcription factors regulate plant defenses in an NPR1
      independent fashion.
AB  - Transcriptional reprogramming during induction of salicylic acid (SA)-mediated
      defenses is regulated primarily by NPR1 (NONEXPRESSOR OF PATHOGENESIS-RELATED
      GENES 1), likely through interactions with TGA bZIP transcription factors. To
      ascertain the contributions of clade I TGA factors (TGA1 and TGA4) to defense
      responses, a tga1-1 tga4-1 double mutant was constructed and challenged with
      Pseudomonas syringae and Hyaloperonospora arabidopsidis. Although the mutant
      displayed enhanced susceptibility to virulent P. syringae, it was not compromised
      in systemic acquired resistance against this pathogen or resistance against
      avirulent H. arabidopsidis. Microarray analysis of nonelicited and SA-treated
      plants indicated that clade I TGA factors regulate fewer genes than NPR1.
      Approximately half of TGA-dependent genes were regulated by NPR1 but, in all
      cases, the direction of change was opposite in the two mutants. In support of the
      microarray data, the NPR1-independent disease resistance observed in the
      autoimmune resistance (R) gene mutant snc1 is partly compromised by tga1-1 tga4-1
      mutations, and a triple mutant of clade I TGA factors with npr1-1 is more
      susceptible than either parent. These results suggest that clade I TGA factors
      are required for resistance against virulent pathogens and avirulent pathogens
      mediated by at least some R gene specificities, acting substantially through NPR1
      independent pathways.

PMID- 22876962
TI  - Isolation of whole esophageal gland cells from plant-parasitic nematodes for
      transcriptome analyses and effector identification.
AB  - Esophageal glands of plant-parasitic nematodes are highly specialized cells whose
      gene expression products include secreted effector proteins, which govern
      nematode parasitism of host plants. Therefore, elucidating the transcriptomes of
      esophageal glands with the goal of identifying nematode effectors is a promising
      avenue to understanding nematode parasitism and its evolutionary origins as well
      as to devising nematode control strategies. We have developed a method to
      separate and isolate individual esophageal gland cells from multiple species of
      plant-parasitic nematodes while preserving RNA quality. We have used such
      isolated gland cells for transcriptome analysis via high-throughput DNA
      sequencing. This method relies on the differential histochemical staining of the
      gland cells after homogenization of phytonematode tissues. Total RNA was
      extracted from whole gland cells isolated from eight different plant-parasitic
      nematode species. To validate this approach, the isolated RNA from three plant
      parasitic nematode species-Globodera rostochiensis, Pratylenchus penetrans, and
      Radopholus similis-was amplified, gel purified, and used for 454 sequencing. We
      obtained 456,801 total reads with an average read length of 409 bp. Sequence
      analyses revealed the presence of homologs of previously known nematode effectors
      in these libraries, thus validating our approach. These data provide compelling
      evidence that this technical advance can be used to relatively easily and
      expediently discover effector repertoires of plant-parasitic nematodes.

PMID- 22876963
TI  - Metavanadate at the active site of the phosphatase VHZ.
AB  - Vanadate is a potent modulator of a number of biological processes and has been
      shown by crystal structures and NMR spectroscopy to interact with numerous
      enzymes. Although these effects often occur under conditions where oligomeric
      forms dominate, the crystal structures and NMR data suggest that the inhibitory
      form is usually monomeric orthovanadate, a particularly good inhibitor of
      phosphatases because of its ability to form stable trigonal-bipyramidal
      complexes. We performed a computational analysis of a 1.14 A structure of the
      phosphatase VHZ in complex with an unusual metavanadate species and compared it
      with two classical trigonal-bipyramidal vanadate-phosphatase complexes. The
      results support extensive delocalized bonding to the apical ligands in the
      classical structures. In contrast, in the VHZ metavanadate complex, the central,
      planar VO(3)(-) moiety has only one apical ligand, the nucleophilic Cys95, and a
      gap in electron density between V and S. A computational analysis showed that the
      V-S interaction is primarily ionic. A mechanism is proposed to explain the
      formation of metavanadate in the active site from a dimeric vanadate species that
      previous crystallographic evidence has shown to be able to bind to the active
      sites of phosphatases related to VHZ. Together, the results show that the
      interaction of vanadate with biological systems is not solely reliant upon the
      prior formation of a particular inhibitory form in solution. The catalytic
      properties of an enzyme may act upon the oligomeric forms primarily present in
      solution to generate species such as the metavanadate ion observed in the VHZ
      structure.

PMID- 22876964
TI  - The technique of single stage pure robotic nephroureterectomy.
AB  - PURPOSE: To describe a novel technique for a single setup approach for robotic
      radical nephroureterectomy (RANU) that does not require patient repositioning,
      port reassignment, or redocking of the robotic arms. MATERIALS AND METHODS:
      Twenty consecutive patients underwent RANU at a single institution between
      January 2009 and January 2012. We implemented a unique port placement strategy
      based on a modified paramedian line (MPL), which allowed sufficient access to
      both the upper abdomen and the deep pelvis for radical NU with bladder cuff
      excision and concomitant lymphadenectomy. RESULTS: The mean operative time was
      161.3 minutes (range 91-330 minutes), mean estimated blood loss was 98.8 (range
      50-200), and the mean hospital stay was 3 days (median 2 days, range 1-16 days).
      None of the procedures were converted to open or required blood transfusions.
      Lymphadenectomy was performed on 16 out of 20 patients, and the mean number of
      lymph nodes removed per patient when lymphadenectomy was performed was 14.1
      (range 2-35). Three patients had positive lymph nodes. One patient had prolonged
      postoperative ileus, and one had a hospital course that was complicated by
      pneumonia. Mean patient follow-up was 13.5 months (range 1-24 months); one
      patient was found to have a recurrence at 3 month follow-up. CONCLUSION: The use
      of our MPL line for novel port placement allows for an effective, efficient, and
      reproducible method for RANU without the need for repositioning of the patient or
      the robot.

PMID- 22876965
TI  - Highly sensitive method for assay of drug-induced apoptosis using fluorescence
      correlation spectroscopy.
AB  - Apoptosis plays a crucial role in many biological processes and pathogenesis of
      various malignancies and diseases of the immune system. In this paper, we
      described a novel method for sensitive detection of drug-induced apoptosis by
      using fluorescence correlation spectroscopy (FCS). The principle of this method
      is based on the assay of DNA fragmentation in the process of the drug-induced
      apoptosis. FCS is a single molecule method, and it can be used for sensitive and
      selective assay of DNA fragmentation without separation. We first developed a
      highly sensitive method for characterization of DNA fragments using a home-built
      FCS system and SYBR Green I as fluorescent DNA-intercalating dye, and then
      established a model of drug-induced apoptosis using human pancreatic cancer cells
      and a drug lidamycin. Furthermore, FCS method established was used to directly
      detect the fragmentation of DNA extracted from apoptotic cells or in the
      apoptotic cell lysate. In FCS assay, the single-component model and the multiple
      components model were used to fit raw FCS data. The characteristic diffusion time
      of DNA fragments was used as an important parameter to distinguish the apoptotic
      status of cells. The obtained data documented that the characteristic diffusion
      time of DNA fragments from apoptotic cells significantly decreased with an
      increase of lidamycin concentration, which implied that DNA fragmentation
      occurred in lidamycin-induced apoptosis. The FCS results are well in line with
      the data obtained from flow cytometer and gel electrophoresis. Compared to
      current methods, the method described here is sensitive and simple, and more
      importantly, our detection volume is less than 1 fL, and the sample requirement
      can easily be reduced to nL level using a droplets array technology. Therefore,
      our method probably becomes a high throughput detection platform for early
      detection of cell apoptosis and screening of apoptosis-based anticancer drugs.

PMID- 22876966
TI  - Size at birth and insulin-like growth factor-I and its binding protein-1 among
      infants of diabetic mothers.
AB  - OBJECTIVE: to estimate the association between intrauterine fetal growth,
      evaluated by anthropometric measurements, and biochemical growth factors; IGF-I
      and IGBP-1 among IDMs. METHODS: Cross-sectional study carried out on 69 full term
      IDMs who was admitted to neonatal intensive care units, Ain Shams University
      Hospitals. Clinical examination including anthropometric measurements; birth
      weight, length, head circumference, mid-arm circumference, skinfold thickness at
      triceps and subscapular areas and placental weight. Laboratory investigations
      included maternal HbA(1c) and cord blood IGF-I and IGBP-1. They were classified
      into three groups: 20 small for gestational age (SGA), 25 appropriate for
      gestational age (AGA) and 24 large for gestational age (LGA). RESULTS: Most of
      SGA neonates were born to mothers with type I diabetes, while most of AGA and LGA
      were born to mothers with gestational diabetes. According to maternal HbA(1c),
      SGA and LGA neonates were born to metabolically uncontrolled mothers while AGA
      neonates were born to well-controlled diabetic mothers. Anthropometric
      measurements had significant positive correlations with IGF-I and negative
      correlations with IGFBP-1. CONCLUSIONS: Good control of diabetes during pregnancy
      is essential to improve fetal growth. There is an opposing effect of cord blood
      IGF-I and IGFBP-1 on anthropometric measurements.

PMID- 22876967
TI  - The intrinsic stability of the human prion beta-sheet region investigated by
      molecular dynamics.
AB  - Human prion diseases are neurodegenerative disorders associated to the misfolding
      of the prion protein (PrP). Common features of prion disorders are the fibrillar
      amyloid deposits and the formation of prefibrillar oligomeric species also
      suggested as the origin of cytotoxicity associated with diseases. Although the
      process of PrP misfolding has been extensively investigated, many crucial aspects
      of this process remain unclear. We have here carried out a molecular dynamics
      study to evaluate the intrinsic dynamics of PrP beta-sheet, a region that is
      believed to play a crucial role in prion aggregation. Moreover, as this region
      mediates protein association in dimeric assemblies frequently observed in prion
      crystallographic investigations, we also analyzed the dynamics of these
      intermolecular interactions. The extensive sampling of replica exchange shows
      that the native antiparallel beta-structure of the prion is endowed with a
      remarkable stability. Therefore, upon unfolding, the persistence of a structured
      beta-region may seed molecular association and influence the subsequent phases of
      the aggregation process. The analysis of the four-stranded beta-sheet detected in
      the dimeric assemblies of PrP shows a tendency of this region to form dynamical
      structured states. The impact on the beta-sheet structure and dynamics of disease
      associated point mutations has also been evaluated.

PMID- 22876968
TI  - QTL analysis of novel genomic regions associated with yield and yield related
      traits in new plant type based recombinant inbred lines of rice (Oryza sativa
      L.).
AB  - BACKGROUND: Rice is staple food for more than half of the world's population
      including two billion Asians, who obtain 60-70% of their energy intake from rice
      and its derivatives. To meet the growing demand from human population, rice
      varieties with higher yield potential and greater yield stability need to be
      developed. The favourable alleles for yield and yield contributing traits are
      distributed among two subspecies i.e., indica and japonica of cultivated rice
      (Oryza sativa L.). Identification of novel favourable alleles in indica/japonica
      will pave way to marker-assisted mobilization of these alleles in to a genetic
      background to break genetic barriers to yield. RESULTS: A new plant type (NPT)
      based mapping population of 310 recombinant inbred lines (RILs) was used to map
      novel genomic regions and QTL hotspots influencing yield and eleven yield
      component traits. We identified major quantitative trait loci (QTLs) for days to
      50% flowering (R2 = 25%, LOD = 14.3), panicles per plant (R2 = 19%, LOD = 9.74),
      flag leaf length (R2 = 22%, LOD = 3.05), flag leaf width (R2 = 53%, LOD = 46.5),
      spikelets per panicle (R2 = 16%, LOD = 13.8), filled grains per panicle (R2 =
      22%, LOD = 15.3), percent spikelet sterility (R2 = 18%, LOD = 14.24), thousand
      grain weight (R2 = 25%, LOD = 12.9) and spikelet setting density (R2 = 23%, LOD =
      15) expressing over two or more locations by using composite interval mapping.
      The phenotypic variation (R2) ranged from 8 to 53% for eleven QTLs expressing
      across all three locations. 19 novel QTLs were contributed by the NPT parent,
      Pusa1266. 15 QTL hotpots on eight chromosomes were identified for the correlated
      traits. Six epistatic QTLs effecting five traits at two locations were
      identified. A marker interval (RM3276-RM5709) on chromosome 4 harboring major
      QTLs for four traits was identified. CONCLUSIONS: The present study reveals that
      favourable alleles for yield and yield contributing traits were distributed among
      two subspecies of rice and QTLs were co-localized in different genomic regions.
      QTL hotspots will be useful for understanding the common genetic control
      mechanism of the co-localized traits and selection for beneficial allele at these
      loci will result in a cumulative increase in yield due to the integrative
      positive effect of various QTLs. The information generated in the present study
      will be useful to fine map and to identify the genes underlying major robust QTLs
      and to transfer all favourable QTLs to one genetic background to break genetic
      barriers to yield for sustained food security.

PMID- 22876970
TI  - Sensitization to methylisothiazolinone in a group of
      methylchloroisothiazolinone/methylisothiazolinone allergic patients.
AB  - In the EU, Methylisothiazolinone (MI) was approved as a preservative in cosmetics
      and household products in 2005. Since then, several cases of MI contact allergy
      have been reported. We studied the prevalence of MI sensitization in patients
      allergic to Methylchloroisothiazolinone/Methylisothiazolinone (MCI/MI). From a
      total of 751 patients submitted to patch testing between 2007 and 2011, 26 were
      sensitized to MCI/MI 100 ppm aq. Fifteen patients were retested with MCI/MI 100
      ppm aq, MI 200 ppm aq and personal products, and the relevance of positive
      results, concerning the use of personal products, was evaluated. Seven of the 15
      MCI/MI positive patients were positive to MI: six patients showed an equally
      intense reaction to MCI/MI and MI alone, and another one presented with a
      stronger reaction to the latter compound. All positive reactions were relevant.
      The use of MI alone as a preservative does not seem to be a safe alternative. In
      this study, the majority of positive reactions to MCI/MI and MI had similar
      intensity, although primary sensitization to MI has to be considered according to
      each individual case; moreover, primary sensitization to MCI with cross
      reactivity to MI cannot be excluded. Further studies are needed to determine the
      optimal concentration for MI patch testing.

PMID- 22876969
TI  - Steroid biotransformations in biphasic systems with Yarrowia lipolytica
      expressing human liver cytochrome P450 genes.
AB  - BACKGROUND: Yarrowia lipolytica efficiently metabolizes and assimilates
      hydrophobic compounds such as n-alkanes and fatty acids. Efficient substrate
      uptake is enabled by naturally secreted emulsifiers and a modified cell surface
      hydrophobicity and protrusions formed by this yeast. We were examining the
      potential of recombinant Y. lipolytica as a biocatalyst for the oxidation of
      hardly soluble hydrophobic steroids. Furthermore, two-liquid biphasic culture
      systems were evaluated to increase substrate availability. While cells, together
      with water soluble nutrients, are maintained in the aqueous phase, substrates and
      most of the products are contained in a second water-immiscible organic solvent
      phase. RESULTS: For the first time we have co-expressed the human cytochromes
      P450 2D6 and 3A4 genes in Y. lipolytica together with human cytochrome P450
      reductase (hCPR) or Y. lipolytica cytochrome P450 reductase (YlCPR). These whole
      cell biocatalysts were used for the conversion of poorly soluble steroids in
      biphasic systems.Employing a biphasic system with the organic solvent and Y.
      lipolytica carbon source ethyl oleate for the whole-cell bioconversion of
      progesterone, the initial specific hydroxylation rate in a 1.5 L stirred tank
      bioreactor was further increased 2-fold. Furthermore, the product formation was
      significantly prolonged as compared to the aqueous system. Co-expression of the
      human CPR gene led to a 4-10-fold higher specific activity, compared to the co
      overexpression of the native Y. lipolytica CPR gene. Multicopy transformants
      showed a 50-70-fold increase of activity as compared to single copy strains.
      CONCLUSIONS: Alkane-assimilating yeast Y. lipolytica, coupled with the described
      expression strategies, demonstrated its high potential for biotransformations of
      hydrophobic substrates in two-liquid biphasic systems. Especially organic
      solvents which can be efficiently taken up and/or metabolized by the cell might
      enable more efficient bioconversion as compared to aqueous systems and even
      enable simple, continuous or at least high yield long time processes.

PMID- 22876971
TI  - Mesenchymal stem cell interactions with 3D ECM modules fabricated via multiphoton
      excited photochemistry.
AB  - To understand complex micro/nanoscale ECM stem cell interactions, reproducible in
      vitro models are needed that can strictly recapitulate the relative content and
      spatial arrangement of native tissue. Additionally, whole ECM proteins are
      required to most accurately reflect native binding dynamics. To address this
      need, we use multiphoton excited photochemistry to create 3D whole protein
      constructs or "modules" to study how the ECM governs stem cell migration. The
      constructs were created from mixtures of BSA/laminin (LN) and BSA alone, whose
      comparison afforded studying how the migration dynamics are governed from the
      combination of morphological and ECM cues. We found that mesenchymal stem cells
      interacted for significantly longer durations with the BSA/LN constructs than
      pure BSA, pointing to the importance of binding cues of the LN. Critical to this
      work was the development of an automated system with feedback based on
      fluorescence imaging to provide quality control when synthesizing multiple
      identical constructs.

PMID- 22876972
TI  - Hypoxic preconditioning enhances the therapeutic potential of the secretome from
      cultured human mesenchymal stem cells in experimental traumatic brain injury.
AB  - Bone-marrow-derived human MSCs (mesenchymal stem cells) support repair when
      administered to animals with TBI (traumatic brain injury) in large part through
      secreted trophic factors. We directly tested the ability of the culture medium
      (or secretome) collected from human MSCs under normoxic or hypoxic conditions to
      protect neurons in a rat model of TBI. Concentrated conditioned medium from
      cultured human MSCs or control medium was infused through the tail vein of rats
      subjected to TBI. We have demonstrated that MSCs cultured in hypoxia were
      superior to those cultured in normoxia in inducing expression of both HGF
      (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) in the
      cultured medium. We showed further that rats treated with the secretome from both
      normoxic- and hypoxic-preconditioned MSCs performed significantly better than the
      controls in both motor and cognitive functional test. Subsequent post-mortem
      evaluation of brain damage at the 4-day time point confirmed that both normoxic-
      and hypoxic-preconditioned MSC secretome-treated rats had significantly greater
      numbers of newly forming neurons, but significantly less than the controls in
      brain damaged volume and apoptosis. The TBI rats treated with hypoxic
      preconditioned MSC secretome performed significantly better in both motor and
      cognitive function tests and neurogenesis, and had significantly less brain
      damage than the TBI rats treated with the normoxic-preconditioned MSC secretome.
      Collectively, these findings suggest that MSCs secrete bioactive factors,
      including HGF and VEGF, that stimulate neurogenesis and improve outcomes of TBI
      in a rat model. Hypoxic preconditioning enhances the secretion of these bioactive
      factors from the MSCs and the therapeutic potential of the cultured MSC secretome
      in experimental TBI.

PMID- 22876973
TI  - Facile, selective, and regiocontrolled synthesis of oxazolines and oxazoles
      mediated by ZnI2 and FeCl3.
AB  - An expedient method for a direct approach to the selective and regiocontrolled
      synthesis of 2-oxazolines and 2-oxazoles mediated by ZnI(2) and FeCl(3) is
      described. A Lewis acid promoted cyclization of acetylenic amide with various
      functionalities was well tolerated to give 2-oxazolines and 2-oxazoles in good to
      excellent yields under mild reaction conditions.

PMID- 22876974
TI  - Self-evaluation in schizophrenia: an fMRI study with implications for the
      understanding of insight.
AB  - BACKGROUND: Lack of insight is a core feature of schizophrenia and is associated
      with structural brain abnormalities. The functional neuroanatomy of insight has
      only recently been investigated. When people evaluate their personality traits
      compared to those of another, activation is seen in central midline structures
      (CMS) of the brain. This study set out to compare cerebral activation in
      schizophrenia patients versus controls during a self-evaluation task which
      included positive and negative traits as well as mental and physical illness
      terms. METHODS: Eleven schizophrenia patients and 8 healthy controls, matched for
      age were studied. Insight was assessed using the Schedule for the Assessment of
      Insight-expanded version (SAI-E). FMRI data were obtained with a 1.5 Tesla GE
      system and interactions between participant group, self versus other, significant
      at the cluster level, were recorded. RESULTS: Significant hypoactivation in the
      medial superior frontal gyrus (dorsomedial prefrontal cortex) was observed in
      patients vs. controls during self-evaluation of all traits combined. A second
      cluster of hypoactivation in the posterior cingulate was also detected. When the
      response to individual traits was explored, underactivation in other frontal
      regions plus right inferior parietal lobule emerged and this tended to correlate,
      albeit weakly with lower insight scores. Further, there were areas of
      hyperactivation relative to controls in anterior cingulate, frontal and parietal
      regions (especially precuneus) which showed moderate inverse correlations with
      insight scores. CONCLUSIONS: We have demonstrated that the CMS, identified as a
      key system underpinning self-evaluation, is dysfunctional in patients with
      schizophrenia, particularly dorso-medial PFC. This may have implications for lack
      of insight in schizophrenia. Hypofunction within the dorsomedial prefrontal
      region seems to be particularly important although other posterior and lateral
      cortical regions play a part and may modulate self-evaluative responses depending
      on the type of trait under consideration.

PMID- 22876975
TI  - Synthesis of multivalent neoglyconjugates of MUC1 by the conjugation of
      carbohydrate-centered, triazole-linked glycoclusters to MUC1 peptides using click
      chemistry.
AB  - The efficient synthesis of multivalent neoglycoconjugates of MUC1 is reported,
      which utilizes Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuACC) of
      azide-functionalized GlcNAc-centered neoglycotetrasaccharide clusters to the MUC1
      peptide sequence that was equipped with a propargylglycine residue for "click
      chemistry". In turn the azido-GlcNAc-centered neoglycoclusters were assembled by
      reaction of a GlcNAc core containing peripheral propargyl functionalities with an
      appropriate azido-functionalized monosaccharide. The resulting suitably
      substituted tetrasaccharyl triazole cluster can be easily appended to a range of
      acetylene-functionalized peptides to produce neoglycoconjugates of biologically
      important glycopeptides. As proof of principle, the click neoglycoclusters
      prepared herein were ligated to the MUC1 peptide sequence.

PMID- 22876977
TI  - Quality- and dilution losses in the recycling of ferrous materials from end-of
      life passenger cars: input-output analysis under explicit consideration of scrap
      quality.
AB  - Metals can in theory be infinitely recycled in a closed-loop without any
      degradation in quality. In reality, however, open-loop recycling is more typical
      for metal scrap recovered from end-of-life (EoL) products because mixing of
      different metal species results in scrap quality that no longer matches the
      originals. Further losses occur when meeting the quality requirement of the
      target product requires dilution of the secondary material by adding high purity
      materials. Standard LCA usually does not address these losses. This paper
      presents a novel approach to quantifying quality- and dilution losses, by means
      of hybrid input-output analysis. We focus on the losses associated with the
      recycling of ferrous materials from end-of-life vehicle (ELV) due to the mixing
      of copper, a typical contaminant in steel recycling. Given the quality of scrap
      in terms of copper density, the model determines the ratio by which scrap needs
      to be diluted in an electric arc furnace (EAF), and the amount of demand for EAF
      steel including those quantities needed for dilution. Application to a high
      resolution Japanese IO table supplemented with data on ferrous materials
      including different grades of scrap indicates that a nationwide avoidance of
      these losses could result in a significant reduction of CO(2) emissions.

PMID- 22876976
TI  - Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and
      adenocarcinomas from Japanese patients.
AB  - BACKGROUND: Merkel cell polyomavirus (MCPyV) was identified originally in Merkel
      cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma.
      Evidence of MCPyV existence in other forms of malignancy such as cutaneous
      squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of
      our interest in searching for potentially MCPyV-related tumors because: (i) the
      major histological type of cervical cancer is the SCC; (ii) the uterine cervix is
      a common site of neuroendocrine carcinomas histologically similar to MCCs; and
      (iii) MCPyV might be transmitted during sexual interaction as demonstrated for
      human papillomavirus (HPV). In this study, we aimed to clarify the possible
      presence of MCPyV in cervical SCCs from Japanese patients. Cervical
      adenocarcinomas (ACs) were also studied. RESULTS: Formalin-fixed paraffin
      embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined
      for the presence of the MCPyV genome by polymerase chain reaction (PCR) and
      sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16
      cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were
      sequenced to compare them with reference sequences. The nucleotide sequences in
      the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive
      cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced
      region, two cervical SCCs and three cervical ACs showed several nucleotide
      substitutions, of which three caused amino acid substitutions. These sequencing
      results suggested that three MCPyV variants of the VP1 were identified in our
      cases. Immunohistochemistry showed that the LT antigen was expressed in tumor
      cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive
      samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV
      types 16 and 18 for ACs. CONCLUSIONS: This study provides the first observation
      that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese
      patients. The prevalence of MCPyV in these lesions was close to that observed in
      the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to
      determine the possible association of MCPyV with pathogenesis of cervical
      cancers.

PMID- 22876978
TI  - Photochemically induced ischemic stroke in rats.
AB  - BACKGROUND: Photothrombosis was introduced as a model of ischemic stroke by
      Watson et al. in 1985. In the present paper, we describe a protocol to induce
      photothrombotic infarcts in rats. FINDINGS: The photosensitive dye Bengal Rose is
      intravenously administered and a laser beam is stereotactically positioned onto
      the skull. Illumination through the intact skull leads to local activation of
      Bengal Rose, which results in free radical formation, disturbance of endothelial
      function and thrombus formation in illuminated small cortical vessels.
      CONCLUSIONS: Photochemically induced infarcts cause long-term sensorimotor
      deficits, allow long-term survival and are particularly suitable to assess the
      effectiveness of neuroregenerative therapies in chronic stroke studies.

PMID- 22876979
TI  - Low molecular weight amidoximes that act as potent inhibitors of lysine-specific
      demethylase 1.
AB  - The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an
      important role in the epigenetic control of gene expression, and aberrant gene
      silencing secondary to LSD1 dysregulation is thought to contribute to the
      development of cancer. We reported that (bis)guanidines, (bis)biguanides, and
      their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the
      re-expression of aberrantly silenced tumor suppressor genes in tumor cells in
      vitro. We now report a series of small molecule amidoximes that are moderate
      inhibitors of recombinant LSD1 but that produce dramatic changes in methylation
      at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in
      Calu-6 lung carcinoma cells. In addition, these analogues increase cellular
      levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the
      transcription factor GATA4. These compounds represent leads for an important new
      series of drug-like epigenetic modulators with the potential for use as antitumor
      agents.

PMID- 22876980
TI  - Health and wellness characteristics of persons with traumatic brain injury.
AB  - OBJECTIVE: To describe health and wellness characteristics of persons with TBI
      living in the community, compare to other disability populations and evaluate the
      associations between health-related constructs. DESIGN: Observational. SETTING:
      Outpatient rehabilitation hospital and a Veterans Affairs Medical Centre.
      PARTICIPANTS: Seventy-four community-dwelling adults with moderate-to-severe TBI.
      INTERVENTIONS: None. MAIN MEASURES: Health Promoting Lifestyle Profile II (HPLP
      II), Self Rated Abilities Health Practices Scale (SRAHP), Barriers to Health
      Promoting Activities for Disabled Scale (BHPAD), Medical Outcomes Study 12-Item
      Health Status Survey Short Form (SF-12), Personal Resource Questionnaire-adapted
      (PRQ-a), Perceived Wellness Survey (PWS), Diener Satisfaction with Life Scale
      (SWLS) and Participation Assessment with Recombined Tools-Objective (PART-O).
      RESULTS: Health-promoting behaviours, self-efficacy and barriers to health were
      comparable to other disability populations. Perceived health status,
      participation and life satisfaction were decreased. Measures of health promotion
      and self-efficacy were positively associated with perceived mental health status,
      life satisfaction and participation. Barriers to healthy activities were
      negatively associated with health promotion, self-efficacy and perceived mental
      health status. CONCLUSIONS: Health and wellness status was below desired levels
      for the study cohort, and comparable to other disability populations. Better
      understanding of associations among health-related constructs is needed.
      Continued research on conceptually-based health and wellness interventions for
      persons with TBI is recommended.

PMID- 22876981
TI  - Therapeutic targeting of VEGF in the treatment of glioblastoma.
AB  - INTRODUCTION: Glioblastoma (GBM) is the most common and aggressive type of
      primary malignant brain tumor in adults. Despite therapy with maximal safe
      surgical resection, radiation and temozolomide, prognosis remains poor at 14.6
      months. Hence, there is an urgent need for developing novel therapeutic agents.
      In GBMs, the balance of angiogenic growth factors is skewed toward pro
      angiogenesis and VEGF is identified as the key growth factor responsible for
      neovasculature. Targeting angiogenesis is hypothesized to arrest tumor growth and
      hence VEGF is an attractive therapeutic target. AREAS COVERED: The purpose of
      this review is to discuss VEGF pathway inhibitors, their efficacy as monotherapy
      or in combination with other drugs, the effects on the radiographic
      response/assessment for GBMs, mechanisms of resistance and associated biomarkers.
      A short summary of angiogenesis and of the biological characteristics of
      angiogenesis will also be provided to enhance the understanding of VEGF pathway
      inhibitors. EXPERT OPINION: Therapeutic targeting of VEGF has lead to
      improvements in progression-free survival in GBM patients without any change in
      the overall survival. VEGF-targeted therapy remains a promising therapeutic
      opportunity if improvements in biomarkers, imaging techniques and rational
      combination therapy are used to help advance the clinical efficacy of this
      approach.

PMID- 22876982
TI  - A note on the nonautonomous delay Beverton-Holt model.
AB  - It is well known that the periodic cycle {x(n)} of a periodically forced
      nonlinear difference equation is attenuant (resonant) if av(x(n)) <
      av(K(n))(av(x(n)) > av(K(n))),where {K ( n )} is the carrying capacity of the
      environment and av(t(n)) = (1/p)?(p-1) (i=0) ti (arithmetic mean of the p
      periodic cycle {t ( n )}). In this article, we extend the concept of attenuance
      and resonance of periodic cycles using the geometric mean for the average of a
      periodic cycle. We study the properties of the periodically forced nonautonomous
      delay Beverton-Holt model x(n+1) = r(n)x(n)/1 + (r(n-l) - 1)x(n-k)/K(n-k), n= 0,
      1, . . . , where {K ( n )} and {r ( n )} are positive p-periodic sequences; (K (
      n )>0, r ( n )>1) as well as k and l are nonnegative integers. We will show that
      for all positive solutions {x ( n )} of the previous equation lim sup (n
      >infinity) (?(n-1)(i=0)xi)(1/n) <= ((?(p-1)(i=0)ri)(1/p) - 1)(?(p-1)(i=0)(ri -
      1))(-1/p)(?(p-1)(i=0)Ki)(1/p). In particular, in the case where {x(n)} is a p
      periodic solution of the above equation (assuming that such solution exists) and
      r ( n )=r>1, the periodic cycle is g-attenuant, that is (?(p
      1)(i=0)x(i))(1/p)<(?(p-1)(i=0)K(i))(p-1) Surprisingly, the obtained results show
      that the delays k and l do not play any role.

PMID- 22876983
TI  - An SEI model for sarcoptic mange among chamois.
AB  - We consider a simple model to study the dynamics of sarcoptic mange in a
      population of chamois. The epidemiological patterns observed during an epidemic
      in Italy are reconstructed and key parameters of the model are estimated from
      field data. In particular, we calculate the basic reproductive ratio R (0), a
      threshold value for chamois density for the occurrence of an epidemic and the
      speed of propagation of the epidemic wave. The model is then used to obtain
      indications on the effect of culling as a possible control measure in a closed
      population and extended to analyse the spatial diffusion of the epidemic. Our
      results are in agreement with mange epidemiology and observations, and suggest
      that intervention could be efficacious in reducing the impact of an epidemic.

PMID- 22876984
TI  - Modelling competition and hybridization between native cutthroat trout and
      nonnative rainbow and hybrid trout.
AB  - Native salmonid fish have been displaced worldwide by nonnatives through
      hybridization, competition, and predation, but the dynamics of these factors are
      poorly understood. We apply stochastic Lotka-Volterra models to the displacement
      of cutthroat trout by rainbow/hybrid trout in the Snake River, Idaho, USA.
      Cutthroat trout are susceptible to hybridization in the river but are
      reproductively isolated in tributaries via removal of migratory rainbow/hybrid
      spawners at weirs. Based on information-theoretic analysis, population data
      provide evidence that hybridization was the primary mechanism for cutthroat trout
      displacement in the first 17 years of the invasion. However, under some parameter
      values, the data provide evidence for a model in which interaction occurs among
      fish from both river and tributary subpopulations. This situation is likely to
      occur when tributary-spawned cutthroat trout out-migrate to the river as fry. The
      resulting competition with rainbow/hybrid trout can result in the extinction of
      cutthroat trout even when reproductive segregation is maintained.

PMID- 22876986
TI  - Toward a classification of isodynamic feed-forward motifs.
AB  - A preceding study analysed how the topology of network motifs affects the overall
      rate of the underlying biochemical processes. Surprisingly, it was shown that
      topologically non-isomorphic motifs can still be isodynamic in the sense that
      they exhibit the exact same performance rate. Because of the high prevalence of
      feed-forward functional modules in biological networks, one may hypothesize that
      evolution tends to favour motifs with faster dynamics. As a step towards ranking
      the efficiency of feed-forward network motifs, we use a linear flow model to
      prove theorems establishing that certain classes of motifs are isodynamic. In
      partitioning the class of all motifs on n nodes into equivalence classes based
      upon their dynamics, we establish a basis for comparing the
      efficiency/performance rates of different motifs. The potential biological
      importance of the theorems is briefly discussed and is the subject of an ongoing
      large-scale project.

PMID- 22876985
TI  - Public vaccination policy using an age-structured model of pneumococcal infection
      dynamics.
AB  - Public health professionals are charged with the task of designing prevention
      programs for the effective control of biologically intricate infectious diseases
      at a population level. The effective vaccination of a population for pneumococcal
      diseases (infections caused by Streptococcus pneumoniae) remains a relevant
      question in the scientific community. It is complicated by heterogeneity in
      individuals' responses to exposure to the bacterium and their responses to
      vaccination. Due to these complexities, most modelling efforts in this area have
      been on the cellular/bacteria level. Here, we introduce an age-structured SEIS
      type model of pneumococcal diseases and their vaccination. We discuss the use of
      this framework in predicting the impact of vaccine strategies, with pneumococcal
      diseases as an example. Using parameter values reasonable for a developed
      country, we discuss the effects of targeting the colonization and/or infection
      stages on the age profiles of morbidity in a population.

PMID- 22876987
TI  - Statistical analysis of a dynamic model for dietary contaminant exposure.
AB  - This paper is devoted to the statistical analysis of a stochastic model
      introduced in [P. Bertail, S. Clemencon, and J. Tressou, A storage model with
      random release rate for modelling exposure to food contaminants, Math. Biosci.
      Eng. 35 (1) (2008), pp. 35-60] for describing the phenomenon of exposure to a
      certain food contaminant. In this modelling, the temporal evolution of the
      contamination exposure is entirely determined by the accumulation phenomenon due
      to successive dietary intakes and the pharmacokinetics governing the elimination
      process inbetween intakes, in such a way that the exposure dynamic through time
      is described as a piecewise deterministic Markov process. Paths of the
      contamination exposure process are scarcely observable in practice, therefore
      intensive computer simulation methods are crucial for estimating the time
      dependent or steady-state features of the process. Here we consider simulation
      estimators based on consumption and contamination data and investigate how to
      construct accurate bootstrap confidence intervals (CI) for certain quantities of
      considerable importance from the epidemiology viewpoint. Special attention is
      also paid to the problem of computing the probability of certain rare events
      related to the exposure process path arising in dietary risk analysis using
      multilevel splitting or importance sampling (IS) techniques. Applications of
      these statistical methods to a collection of data sets related to dietary methyl
      mercury contamination are discussed thoroughly.

PMID- 22876988
TI  - Effectiveness of cognitive remediation therapy (CRT) in anorexia nervosa: a case
      series.
AB  - We investigated whether cognitive remediation therapy (CRT) is effective in
      improving cognitive flexibility in anorexia nervosa (AN). Twenty AN outpatients
      were consecutively recruited at the Eating Disorders Center of the Turin
      University. All participants completed 10 sessions of CRT. Neuropsychological
      performances improved with CRT. Data showed also a significant improvement of
      impulse regulation and interoceptive awareness (subscales of the Eating Disorders
      Inventory-2). CRT was also associated with improvement of reflexive skills and
      awareness. These preliminary findings are promising, but further work is
      necessary to find ways of enhancing the effects of this treatment.

PMID- 22876989
TI  - Efficient greenish blue electrochemiluminescence from fluorene and
      spirobifluorene derivatives.
AB  - The spectroscopic and electrochemical behavior as well as electrogenerated
      chemiluminescence (ECL) of a series of donor-pi-donor derivatives bearing
      triphenylamine groups as donor connected to a fluorene, 2,7-bis-(4-(N,N
      diphenylamino)phen-1-yl)-9,9'-dimethylfluorene (1), or spirobifluorene core, 2,7
      bis-(4-(N,N-diphenylamino)phen-1-yl)-9,9'-spirobifluorene (2) and 2,2',7,7'
      tetrakis(4-(N,N-diphenylamino)phen-1-yl)-9,9'-spirobifluorene (3), were
      investigated. Besides a high photoluminescence (PL) quantum yield in solution
      (between 81 and 87%), an efficient radical ions annihilation process induces
      intense greenish blue ECL emission that could be seen with the naked eye. Only
      the tetrasubstituted spirobifluorene derivative (compound 3) shows weak ECL
      obtained by a direct annihilation mechanism. Because the energy of the
      annihilation reaction is higher than the energy required to form the singlet
      excited state, the S-route could be considered the pathway followed by the ECL
      process in these molecules. The ECL emissions recorded by direct ion-ion
      annihilation show two bands compared to the single structureless PL band. The ECL
      spectra obtained by a coreactant approach using benzoylperoxide  as a coreagent
      show no differences relative to that produced by annihilation, except for an
      increasing of ECL intensity for all compounds.

PMID- 22876990
TI  - Single molecule dynamics on hydrophobic self-assembled monolayers.
AB  - The interactions between adsorbate molecules and hydrophobic surfaces are of
      significant interest due to their importance in a variety of biological and
      separation processes. However, it is challenging to extrapolate macroscopic
      ensemble-averaged force measurements to molecular-level phenomena. Using total
      internal reflection fluorescence microscopy to image individual molecules at
      hydrophobic solid-aqueous interfaces, we directly observed dynamic behavior
      associated with the interactions between fluorescently labeled dodecanoic acid
      (our probe molecules) and self-assembled monolayers (SAM) comprising n
      alkyltriethoxysilanes with systematically increasing chain length (from n = 4
      18). In all cases, we observed at least two characteristic surface residence
      times and two diffusive modes, suggesting the presence of multiple distinct
      adsorbed populations. In general, the mean surface residence time increased and
      the mobility decreased with increasing SAM chain length, consistent with stronger
      probe-surface interactions. However, these trends were not primarily due to
      changes in characteristic residence times or diffusion coefficients associated
      with the individual populations but rather to a dramatic increase in the fraction
      associated with the long-lived slow-moving population(s) on long-chain SAMs. In
      particular, on longer (16-18 carbon) alkylsilane monolayers, the probe molecule
      exhibited far fewer desorption-mediated "flights" than on short (4-6 carbon)
      monolayers. Additionally, probes on the longer chain surfaces were much more
      likely to exhibit extended surface residence times as opposed to short transient
      surface visits.

PMID- 22877077
TI  - Genome-scale identification of cell-wall related genes in Arabidopsis based on co
      expression network analysis.
AB  - BACKGROUND: Identification of the novel genes relevant to plant cell-wall (PCW)
      synthesis represents a highly important and challenging problem. Although
      substantial efforts have been invested into studying this problem, the vast
      majority of the PCW related genes remain unknown. RESULTS: Here we present a
      computational study focused on identification of the novel PCW genes in
      Arabidopsis based on the co-expression analyses of transcriptomic data collected
      under 351 conditions, using a bi-clustering technique. Our analysis identified
      217 highly co-expressed gene clusters (modules) under some experimental
      conditions, each containing at least one gene annotated as PCW related according
      to the Purdue Cell Wall Gene Families database. These co-expression modules cover
      349 known/annotated PCW genes and 2,438 new candidates. For each candidate gene,
      we annotated the specific PCW synthesis stages in which it is involved and
      predicted the detailed function. In addition, for the co-expressed genes in each
      module, we predicted and analyzed their cis regulatory motifs in the promoters
      using our motif discovery pipeline, providing strong evidence that the genes in
      each co-expression module are transcriptionally co-regulated. From the all co
      expression modules, we infer that 108 modules are related to four major PCW
      synthesis components, using three complementary methods. CONCLUSIONS: We believe
      our approach and data presented here will be useful for further identification
      and characterization of PCW genes. All the predicted PCW genes, co-expression
      modules, motifs and their annotations are available at a web-based database:
      http://csbl.bmb.uga.edu/publications/materials/shanwang/CWRPdb/index.html.

PMID- 22877078
TI  - Binding orientation and specificity of calmodulin to rat olfactory cyclic
      nucleotide-gated ion channel.
AB  - Calmodulin (CaM), the primary intracellular Ca(2+) receptor, regulates a large
      number of key enzymes and controls a wide spectrum of important biological
      responses. Recognition between CaM and its target sequence in rat olfactory
      cyclic nucleotide-gated ion channel (OLFp) was investigated by circular dichroism
      (CD), fluorescence, and NMR spectroscopy. Fluorescence data showed the OLFp
      tightly bound to CaM with a dissociation constant of 12 nM in a 1:1
      stoichiometry. Far-UV CD data showed that approximately 60% of OLFp residues
      formed alpha-helical structures when associated with CaM. NMR data showed that
      most of the (15)N-(1)H HSQC cross-peaks of the (15)N-labeled CaM not only shifted
      but also split into two sets of peaks upon association with the OLFp. Our data
      indicated that the two distinct CaM/OLFp complexes existed simultaneously with
      stable structures that were not interexchangeable within the NMR time scale. In
      light of the palindromic sequence of OLFp (FQRIVRLVGVIRDW) for CaM targeting, we
      proposed that the helical OLFp with C2 symmetry may bind to CaM in two
      orientations. This hypothesis is supported by the observation that only one set
      of (15)N-(1)H HSQC cross-peaks of the (15)N-labeled CaM was detected upon
      association with OLFp-M13 chimeric peptide (OLFMp), a mutated OLFp lacking the
      palindromic feature. The binding specificity of OLFMp to CaM was restored when
      the palindromic feature was destroyed. Binding modes of CaM/OLFp and CaM/OLFMp
      simulated by molecular docking were in accord with their distinct patterns
      observed in HSQC spectra. Our studies suggest that the palindromic residues in
      OLFp are crucial for the orientation-specific recognition by CaM.

PMID- 22877079
TI  - Endoreduplication in cervical trophoblast cells from normal pregnancies.
AB  - OBJECTIVE: Fetal cells represented by extravillous trophoblasts (EVT) obtained
      from the cervix by a minimally invasive procedure are important for prenatal
      diagnosis in early pregnancies. Endoreduplication is a duplication of chromosomes
      without mitosis, leading to polyploidy that might represent increased cellular
      metabolic activity. In this study, we estimated the normal prevalence of
      polyploid trophoblasts exfoliated to the cervix between 5 and 13 weeks of
      gestation. METHODS: Cervical samples were obtained by cytobrush, between 5 and 13
      weeks of gestation from 36 randomly selected, singleton pregnancies. FISH was
      done with X, Y and two 21 probes. RESULTS: We diagnosed 21 pregnancies with
      female and 15 pregnancies with male fetal karyotypes. A mean of 15.2 (0.02%)
      tetraploid cells were found in pregnancies with a female fetus and a mean of 2.0
      (0.003%) tetraploid cells were found in pregnancies with a male fetus. The
      tetraploid cells (endoreduplicated trophoblasts) were two to three times larger
      than the normal cells usually seen in the cervix. CONCLUSIONS: Extravillus
      trophoblasts tend to form endoreduplication to the ploidy level of 4c-8c of DNA.
      Those cells may represent a typical phenomenon in the growing placenta.
      Extravillus trophoblasts from female fetuses tend to form higher rates of
      endoreduplication.

PMID- 22877080
TI  - Thermal stability of hydrophobic helical oligomers: a lattice simulation study in
      explicit water.
AB  - We investigate the thermal stability of helical hydrophobic oligomers using a
      three-dimensional, water-explicit lattice model and the Wang-Landau Monte Carlo
      method. The degree of oligomer helicity is controlled by the parameter
      epsilon(mm) < 0, which mimics monomer-monomer hydrogen bond interactions leading
      to the formation of helical turns in atomistic proteins. We vary |epsilon(mm)|
      between 0 and 4.5 kcal/mol and therefore investigate systems ranging from
      flexible homopolymers (i.e., those with no secondary structure) to helical
      oligomers that are stable over a broad range of temperatures. We find that
      systems with |epsilon(mm)| <= 2.0 kcal/mol exhibit a broad thermal unfolding
      transition at high temperature, leading to an ensemble of random coils. In
      contrast, the structure of conformations involved in a second, low-temperature,
      transition is strongly dependent on |epsilon(mm)|. Weakly helical oligomers are
      observed when |epsilon(mm)| <= 1.0 kcal/mol and exhibit a low-temperature, cold
      unfolding-like transition to an ensemble of strongly water-penetrated globular
      conformations. For higher |epsilon(mm)| (1.7 kcal/mol <= |epsilon(mm)| <= 2.0
      kcal/mol), cold unfolding is suppressed, and the low-temperature conformational
      transition becomes a "crystallization", in which a "molten" helix is transformed
      into a defect-free helix. The molten helix preserves >=50% of the helical
      contacts observed in the "crystal" at a lower temperature. When |epsilon(mm)| =
      4.5 kcal/mol, we find that conformational transitions are largely suppressed
      within the range of temperatures investigated.

PMID- 22877081
TI  - Toxic optic neuropathy following ingestion of homeopathic medication Arnica-30.
AB  - We report a case of acute, bilateral and severe vision loss after inadvertent
      consumption of a large quantity of the homoeopathic medication Arnica-30. Severe
      vomiting which required hospitalization preceded visual symptoms. In the acute
      stage, pupillary responses to light were absent and fundus examination was
      normal. Vision loss followed a fluctuating course, with profound loss noted after
      6 weeks along with bilateral optic disc pallor. Neuro-ophthalmic examination and
      detailed investigations were performed, including magnetic resonance imaging,
      electroretinography (ERG) and visual evoked potentials (VEP). Ocular coherence
      tomography (OCT) showed gross thinning of the retinal nerve fiber layer. While a
      differential diagnosis of posterior ischemic optic neuropathy was kept in mind,
      these findings supported a diagnosis of bilateral toxic optic neuropathy. Arnica
      30 is popularly used to accelerate wound healing, including after oculoplastic
      surgery. While homeopathic medicines are generally considered safe due to the
      very low concentrations involved, Arnica-30 may be neurotoxic if consumed
      internally in large quantities.

PMID- 22877083
TI  - Regioselectivity switch: gold(I)-catalyzed oxidative rearrangement of propargyl
      alcohols to 1,3-diketones.
AB  - The gold(I)-catalyzed oxidative rearrangement of propargyl alcohols provides an
      efficient and selective route to 1,3-diketones under mild conditions. Pyridine-N
      oxides were used as external oxidants with, different from related substrates, no
      alkylidenecycloalkanones or oxetan-3-ones formed as side-products.

PMID- 22877084
TI  - Benzylidene-oxazolones as molecular photoswitches.
AB  - The synthesis and photochemical study of a family of molecular switches inspired
      by the green fluorescent protein (GFP) chromophore is presented. These compounds
      can be easily synthesized, and their photophysical properties may be tuned. Due
      to their efficient photoisomerization and high stability, these compounds can be
      switched on/off by using light and heat or light with different wavelengths.

PMID- 22877082
TI  - Review of pyronaridine anti-malarial properties and product characteristics.
AB  - Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic
      Disease and has been used in China for over 30 years for the treatment of
      malaria. Pyronaridine has high potency against Plasmodium falciparum, including
      chloroquine-resistant strains. Studies in various animal models have shown
      pyronaridine to be effective against strains resistant to other anti-malarials,
      including chloroquine. Resistance to pyronaridine appears to emerge slowly and is
      further retarded when pyronaridine is used in combination with other anti
      malarials, in particular, artesunate. Pyronaridine toxicity is generally less
      than that of chloroquine, though evidence of embryotoxicity in rodents suggests
      use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine
      indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and
      children with acute uncomplicated falciparum and vivax malaria in artemisinin
      combination therapy. Clinical data for mono or combined pyronaridine therapy show
      excellent anti-malarial effects against P. falciparum and studies of combination
      therapy also show promise against Plasmodium vivax. Pyronaridine has been
      developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate
      for the treatment of acute uncomplicated P. falciparum malaria and blood stage P.
      vivax malaria with the name of Pyramax(r) and has received Positive Opinion by
      European Medicines Agency under the Article 58 procedure.

PMID- 22877085
TI  - Potent and highly selective benzimidazole inhibitors of PI3-kinase delta.
AB  - Inhibition of PI3Kdelta is considered to be an attractive mechanism for the
      treatment of inflammatory diseases and leukocyte malignancies. Using a structure
      based design approach, we have identified a series of potent and selective
      benzimidazole-based inhibitors of PI3Kdelta. These inhibitors do not occupy the
      selectivity pocket between Trp760 and Met752 that is induced by other families of
      PI3Kdelta inhibitors. Instead, the selectivity of the compounds for inhibition of
      PI3Kdelta relative to other PI3K isoforms appears to be due primarily to the
      strong interactions these inhibitors are able to make with Trp760 in the
      PI3Kdelta binding pocket. The pharmacokinetic properties and the ability of
      compound 5 to inhibit the function of B-cells in vivo are described.

PMID- 22877086
TI  - Neurofeedback for the treatment of children and adolescents with ADHD: a
      randomized and controlled clinical trial using parental reports.
AB  - BACKGROUND: A randomized and controlled clinical study was performed to evaluate
      the use of neurofeedback (NF) to treat attention-deficit/hyperactivity disorder
      (ADHD) in children and adolescents. METHODS: The ADHD population was selected
      from an outpatient clinic for Child and Adolescent Mental Health in Norway.
      Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years
      (10.5 years) participated in 30 sessions of an intensive NF program. The
      reinforcement contingency was based on the subjects' production of cortical beta1
      activity (15-18 Hz). The ADHD participants were randomized into three groups,
      with 30 in the NF group, 31 controls in a group that was given methylphenidate,
      and 30 in a group that received NF and methylphenidate. ADHD core symptoms were
      reported by parents using the parent form of the Clinician's Manual for
      Assessment by Russell A. Barkley. RESULTS: Ninety-one children and adolescents
      were effectively randomized by age, sex, intelligence and distribution of ADHD
      core symptoms. The parents reported significant effects of the treatments, but no
      significant differences between the treatment groups were observed. CONCLUSIONS:
      NF was as effective as methylphenidate at treating the attentional and
      hyperactivity symptoms of ADHD, based on parental reports. TRIAL REGISTRATION:
      Current Controlled Trials NCT01252446.

PMID- 22877087
TI  - Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment
      stimulated antibody responses in hamsters.
AB  - Enterovirus 71 (EV71) causes severe neurological diseases resulting in high
      mortality in young children worldwide. Development of an effective vaccine
      against EV71 infection is hampered by the lack of appropriate animal models for
      efficacy testing of candidate vaccines. Previously, we have successfully tested
      the immunogenicity and protectiveness of a candidate EV71 vaccine, containing
      recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment
      (NPt-VP11-100) protein, in a mouse model of EV71 infection. A drawback of this
      system is its limited window of EV71 susceptibility period, 2 weeks after birth,
      leading to restricted options in the evaluation of optimal dosing regimens. To
      address this issue, we have assessed the NPt-VP11-100 candidate vaccine in a
      hamster system, which offers a 4-week susceptibility period to EV71 infection.
      Results obtained showed that the NPt-VP11-100 candidate vaccine stimulated
      excellent humoral immune response in the hamsters. Despite the high level of
      antibody production, they failed to neutralize EV71 viruses or protect vaccinated
      hamsters in viral challenge studies. Nevertheless, these findings have
      contributed towards a better understanding of the NPt-VP11-100 recombinant
      protein as a candidate vaccine in an alternative animal model system.

PMID- 22877136
TI  - Injectable doubly cross-linked microgels for improving the mechanical properties
      of degenerated intervertebral discs.
AB  - The use of injectable pH-responsive doubly cross-linked microgels (DX microgels)
      to improve the mechanical properties of degenerated intervertebral discs is
      demonstrated for the first time. The microgel comprised methyl methacrylate
      (MMA), methacrylic acid (MAA), ethyleneglycol dimethacrylate (EGD) and glycidyl
      methacrylate (GM) and was poly(MMA/MAA/EGD)-GM. The GM facilitated covalent
      interparticle cross-linking. The DX microgels are shown to have tunable
      mechanical properties. Degeneration of model bovine intervertebral discs (IVDs)
      was induced using collagenase. When injected into degenerated IVDs the DX
      microgels were shown to improve the strain, modulus, toughness and resilience.
      The extent of mechanical property improvement was an increasing function of DX
      microgel concentration, suggesting tunability. Cytotoxicity studies showed that
      the DX microgel was biocompatible under the conditions investigated. The results
      of this study imply that injectable DX microgels have good potential as a future
      regenerative medicine strategy for restoring the mechanical properties of
      degenerated load-bearing soft tissue, such as IVDs.

PMID- 22877137
TI  - Leveraging socially networked mobile ICT platforms for the last-mile delivery
      problem.
AB  - Increasing numbers of people are managing their social networks on mobile
      information and communication technology (ICT) platforms. This study materializes
      these social relationships by leveraging spatial and networked information for
      sharing excess capacity to reduce the environmental impacts associated with "last
      mile" package delivery systems from online purchases, particularly in low
      population density settings. Alternative package pickup location systems (PLS),
      such as a kiosk on a public transit platform or in a grocery store, have been
      suggested as effective strategies for reducing package travel miles and
      greenhouse gas emissions, compared to current door-to-door delivery models (CDS).
      However, our results suggest that a pickup location delivery system operating in
      a suburban setting may actually increase travel miles and emissions. Only once a
      social network is employed to assist in package pickup (SPLS) are significant
      reductions in the last-mile delivery distance and carbon emissions observed
      across both urban and suburban settings. Implications for logistics management's
      decades-long focus on improving efficiencies of dedicated distribution systems
      through specialization, as well as for public policy targeting carbon emissions
      of the transport sector are discussed.

PMID- 22877138
TI  - The uroguanylin system and human disease.
AB  - The uroguanylin system is a newly discovered endocrine/paracrine system that may
      have a role in the regulation of salt balance, appetite and gut health. The
      precursor pro-uroguanylin is predominantly synthesized in the gut, although there
      may be other sites of synthesis, including the kidney tubules. Products from pro
      uroguanylin may mediate natriuresis following oral consumption of a salt load
      through both GC-C (guanylate cyclase C)-dependent and -independent mechanisms,
      and recent evidence suggests a role in appetite regulation. Local paracrine
      effects in the gut through GC-C stimulation may have tumour-suppressing actions
      through the regulation of cell proliferation and metabolism. Although most
      information on this system has been derived from knockout models, recent human
      studies have indicated possible roles in heart failure and renal failure. An
      improved understanding of the nature of its natriuretic, appetite and tumour
      suppressing actions may facilitate the discovery of new therapies for heart
      failure, obesity and cancer prophylaxis.

PMID- 22877139
TI  - Introduction to TBI Model Systems issue.

PMID- 22877140
TI  - Contact networks in epidemiology. Preface.

PMID- 22877141
TI  - Large-scale properties of clustered networks: implications for disease dynamics.
AB  - We consider previously proposed procedures for generating clustered networks and
      investigate how these procedures lead to differences in network properties other
      than clustering. We interpret our findings in terms of the effect of the network
      structure on the disease outbreak threshold and disease dynamics. To generate
      null-model networks for comparison, we implement an assortativity-conserving
      rewiring algorithm that alters the level of clustering while causing minimal
      impact on other properties. We show that many theoretical network models used to
      generate networks with a particular property often lead to significant changes in
      network properties other than that of interest. For high levels of clustering,
      different procedures lead to networks that differ in degree heterogeneity and
      assortativity, and in broader scale measures such as R(0) and the distribution of
      shortest path lengths. Hence, care must be taken when investigating the
      implications of network properties for disease transmission or other dynamic
      process that the network supports.

PMID- 22877142
TI  - Notes from the heterogeneous: a few observations on the implications and
      necessity of affinity.
AB  - The problem of who is mixing with whom is of great theoretical importance in the
      context of heterosexual mixing. In this article, we publish for the first time,
      data from a study carried out in 1989 that had the goal of estimating who is
      mixing with whom, in heterosexually active college populations in the presence of
      co-factors like drinking. The gathering of these data and the challenges involved
      in modelling the interaction between and among heterosexually active populations
      of individuals are highlighted in this manuscript. The modelling is based on the
      assumptions that at least two processes are involved: individual affinities or
      preferences determine 'what we want' while mixing patterns describe 'what we
      get'. We revisit past results on the role of affinity/preference on observed
      mixing patterns in one- and two-sex mixing populations. Some new results for
      homosexually active populations are presented. The study of mixing is but the
      means to an end and consequently, we also look at the role of affinity on
      epidemics as filtered by observed mixing patterns. It would not be surprising to
      observe that highly distinct preference or mixing structures may actually lead to
      quite similar epidemic patterns.

PMID- 22877143
TI  - The dynamic nature of contact networks in infectious disease epidemiology.
AB  - Although contact network models have yielded important insights into infectious
      disease transmission and control throughout the last decade, researchers have
      just begun to explore the dynamic nature of contact patterns and their
      epidemiological significance. Most network models have assumed that contacts are
      static through time. Developing more realistic models of the social interactions
      that underlie the spread of infectious diseases thus remains an important
      challenge for both data gatherers and modelers. In this article, we review some
      recent data-driven and process-driven approaches that capture the dynamics of
      human contact, and discuss future challenges for the field.

PMID- 22877144
TI  - Effect of a sharp change of the incidence function on the dynamics of a simple
      disease.
AB  - We investigate two cases of a sharp change of incidencec functions on the
      dynamics of a susceptible-infective-susceptible epidemic model. In the first
      case, low population levels have mass action incidence, while high population
      levels have proportional incidence, the switch occurring when the total
      population reaches a certain threshold. Using a modified Dulac theorem, we prove
      that this system has a single equilibrium which attracts all solutions for which
      the disease is present and the population remains bounded. In the second case, an
      increase of the number of infectives leads to a mass action term being added to a
      standard incidence term. We show that this allows a Hopf bifurcation to occur,
      with periodic orbits being generated when a locally asymptotically stable
      equilibrium loses stability.

PMID- 22877145
TI  - The dynamics of an epidemic model with targeted antiviral prophylaxis.
AB  - Due to the increasing risk of drug resistance and side effects with large-scale
      antiviral use, it has been suggested to provide antiviral drugs only to
      susceptibles who have had contacts with infectives. This antiviral distribution
      strategy is referred to as 'targeted antiviral prophylaxis'. The question of how
      effective this strategy is in infection control is of great public heath
      interest. In this paper, we formulate an ordinary differential equation model to
      describe the transmission dynamics of infectious disease with targeted antiviral
      prophylaxis, and provide the analysis of dynamical behaviours of the model. The
      control reproduction number R(c) is derived and shown to govern the disease
      dynamics, and the stability analysis is carried out. The local bifurcation theory
      is applied to explore the variety of dynamics of the model. Our theoretical
      results show that the system undergoes two Hopf bifurcations due to the existence
      of multiple endemic equilibria and the switch of their stability. Numerical
      results demonstrate that the system may have more complex dynamical behaviours
      including multiple periodic solutions and a homoclinic orbit. The results of this
      study suggest that the possibility of complex disease dynamics can be driven by
      the use of targeted antiviral prophylaxis, and the critical level of prophylaxis
      which achieves R(c)=1 is not enough to control the prevalence of a disease.

PMID- 22877146
TI  - Genome-wide mapping of NBS-LRR genes and their association with disease
      resistance in soybean.
AB  - BACKGROUND: R genes are a key component of genetic interactions between plants
      and biotrophic bacteria and are known to regulate resistance against bacterial
      invasion. The most common R proteins contain a nucleotide-binding site and a
      leucine-rich repeat (NBS-LRR) domain. Some NBS-LRR genes in the soybean genome
      have also been reported to function in disease resistance. In this study, the
      number of NBS-LRR genes was found to correlate with the number of disease
      resistance quantitative trait loci (QTL) that flank these genes in each
      chromosome. NBS-LRR genes co-localized with disease resistance QTL. The study
      also addressed the functional redundancy of disease resistance on recently
      duplicated regions that harbor NBS-LRR genes and NBS-LRR gene expression in the
      bacterial leaf pustule (BLP)-induced soybean transcriptome. RESULTS: A total of
      319 genes were determined to be putative NBS-LRR genes in the soybean genome. The
      number of NBS-LRR genes on each chromosome was highly correlated with the number
      of disease resistance QTL in the 2-Mb flanking regions of NBS-LRR genes. In
      addition, the recently duplicated regions contained duplicated NBS-LRR genes and
      duplicated disease resistance QTL, and possessed either an uneven or even number
      of NBS-LRR genes on each side. The significant difference in NBS-LRR gene
      expression between a resistant near-isogenic line (NIL) and a susceptible NIL
      after inoculation of Xanthomonas axonopodis pv. glycines supports the conjecture
      that NBS-LRR genes have disease resistance functions in the soybean genome.
      CONCLUSIONS: The number of NBS-LRR genes and disease resistance QTL in the 2-Mb
      flanking regions of each chromosome was significantly correlated, and several
      recently duplicated regions that contain NBS-LRR genes harbored disease
      resistance QTL for both sides. In addition, NBS-LRR gene expression was
      significantly different between the BLP-resistant NIL and the BLP-susceptible NIL
      in response to bacterial infection. From these observations, NBS-LRR genes are
      suggested to contribute to disease resistance in soybean. Moreover, we propose
      models for how NBS-LRR genes were duplicated, and apply Ks values for each NBS
      LRR gene cluster.

PMID- 22877147
TI  - Targeting CSCs within the tumor microenvironment for cancer therapy: a potential
      role of mesenchymal stem cells.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) are one subgroup of adult stem cells
      and possess a proliferative potential and ability to differentiate into various
      ceells. AREAS COVERED: Emerging evidence suggests that MSCs can reprogram toward
      cancer stem cells (CSCs), due to alterations of intrinsic and extrinsic
      microenvironments, leading to tumorigenesis. The CSC concept has fundamental
      clinical implications because of its involvement in cell migration/invasion,
      metastasis, and treatment resistance. Therefore, targeting CSCs provides a novel
      therapeutic strategy for cancer treatment. However, the origin of CSCs and its
      molecular connections are not fully understood. Emerging evidence suggests the
      existence of an inter-relationship between CSCs and epithelial-to-mesenchymal
      transition (EMT) phenotypic cells, in the context of inflammation and hypoxia, as
      well as the potential role of miRNAs. EXPERT OPINION: We suggest that targeting
      CSC signatures along with EMT, inflammation, and hypoxia will provide a more
      effective therapeutic approach for the elimination of CSCs. To that end, curcumin
      especially its synthetic novel analog CDF have been shown to attenuate CSC
      characteristics along with the deregulation of multiple pathways and miRNAs,
      leading to the inhibition of human tumor growth in vivo, suggesting the potential
      role of CDF as an anti-tumor agent for the prevention/treatment of tumor
      progression.

PMID- 22877148
TI  - Dissecting the function of a protruding loop in AcrB trimerization.
AB  - The resistance-nodulation-cell division family multidrug transporter Acriflavine
      resistance protein B (AcrB) from Eschericha coli is an obligate homotrimer.
      Approximately, 45% of the inter-subunit interface is contributed by a protruding
      loop (also referred to as the thumb) and its corresponding binding tunnel in the
      neighboring subunit. In an earlier study, we have demonstrated that a single Pro
      to Gly mutation in the loop drastically destabilized AcrB trimer and reduced its
      substrate efflux activity. To further dissect the role of the loop during AcrB
      trimerization, we performed Ala scanning of the loop and examined the effect of
      each mutation on protein activity. We found that not all conserved residues are
      important for AcrB function and likewise not all critical residues are conserved.
      In addition, we replaced the loop of AcrB with the loop of MexB, which is a
      highly conserved homolog of AcrB. The resultant chimeric protein remained partly
      active. Structural characterization of the chimeric protein indicated that it was
      well folded and existed as a mixture of monomer and trimer. Our results indicate
      that the loop to tunnel interaction, while critical to trimerization and efflux
      function, is in general rather flexible and tolerant to mutations. In addition,
      all mutations in the loop that resulted in reduced function clustered closely,
      suggesting that this may be the site of inter-subunit recognition during
      trimerization and/or a locking zone to stabilize the inter-subunit interaction
      during trimerization.

PMID- 22877149
TI  - Development of an embryonic skeletogenic mesenchyme lineage in a sea cucumber
      reveals the trajectory of change for the evolution of novel structures in
      echinoderms.
AB  - BACKGROUND: The mechanisms by which the conserved genetic "toolkit" for
      development generates phenotypic disparity across metazoans is poorly understood.
      Echinoderm larvae provide a great resource for understanding how developmental
      novelty arises. The sea urchin pluteus larva is dramatically different from basal
      echinoderm larval types, which include the auricularia-type larva of its sister
      taxon, the sea cucumbers, and the sea star bipinnaria larva. In particular, the
      pluteus has a mesodermally-derived larval skeleton that is not present in sea
      star larvae or any outgroup taxa. To understand the evolutionary origin of this
      structure, we examined the molecular development of mesoderm in the sea cucumber,
      Parastichopus parvimensis. RESULTS: By comparing gene expression in sea urchins,
      sea cucumbers and sea stars, we partially reconstructed the mesodermal regulatory
      state of the echinoderm ancestor. Surprisingly, we also identified expression of
      the transcription factor alx1 in a cryptic skeletogenic mesenchyme lineage in P.
      parvimensis. Orthologs of alx1 are expressed exclusively within the sea urchin
      skeletogenic mesenchyme, but are not expressed in the mesenchyme of the sea star,
      which suggests that alx1+ mesenchyme is a synapomorphy of at least sea urchins
      and sea cucumbers. Perturbation of Alx1 demonstrates that this protein is
      necessary for the formation of the sea cucumber spicule. Overexpression of the
      sea star alx1 ortholog in sea urchins is sufficient to induce additional
      skeleton, indicating that the Alx1 protein has not evolved a new function during
      the evolution of the larval skeleton. CONCLUSIONS: The proposed echinoderm
      ancestral mesoderm state is highly conserved between the morphologically similar,
      but evolutionarily distant, auricularia and bipinnaria larvae. However, the
      auricularia, but not bipinnaria, also develops a simple skelotogenic cell
      lineage. Our data indicate that the first step in acquiring these novel cell
      fates was to re-specify the ancestral mesoderm into molecularly distinct
      territories. These new territories likely consisted of only a few cells with few
      regulatory differences from the ancestral state, thereby leaving the remaining
      mesoderm to retain its original function. The new territories were then free to
      take on a new fate. Partitioning of existing gene networks was a necessary pre
      requisite to establish novelty in this system.

PMID- 22877150
TI  - Variable-temperature 17O NMR studies allow quantitative evaluation of molecular
      dynamics in organic solids.
AB  - We report a comprehensive variable-temperature solid-state (17)O NMR study of
      three (17)O-labeled crystalline sulfonic acids: 2-aminoethane-1-sulfonic acid
      (taurine, T), 3-aminopropane-1-sulfonic acid (homotaurine, HT), and 4-aminobutane
      1-sulfonic acid (ABSA). In the solid state, all three compounds exist as
      zwitterionic structures, NH(3)(+)-R-SO(3)(-), in which the SO(3)(-) group is
      involved in various degrees of O...H-N hydrogen bonding. High-quality (17)O NMR
      spectra have been obtained for all three compounds under both static and magic
      angle spinning (MAS) conditions at 21.1 T, allowing the complete set of (17)O NMR
      tensor parameters to be measured. Assignment of the observed (17)O NMR parameters
      to the correct oxygen sites in the crystal lattice was achieved with the aid of
      DFT calculations. By modeling the temperature dependence of (17)O NMR powder line
      shapes, we have not only confirmed that the SO(3)(-) groups in these compounds
      undergo a 3-fold rotational jump mechanism but also extracted the corresponding
      jump rates (10(2)-10(5) s(-1)) and the associated activation energies (E(a)) for
      this process (E(a) = 48 +/- 7, 42 +/- 3, and 45 +/- 1 kJ mol(-1) for T, HT, and
      ABSA, respectively). This is the first time that SO(3)(-) rotational dynamics
      have been directly probed by solid-state (17)O NMR. Using the experimental
      activation energies for SO(3)(-) rotation, we were able to evaluate
      quantitatively the total hydrogen bond energy that each SO(3)(-) group is
      involved in within the crystal lattice. The activation energies also correlate
      with calculated rotational energy barriers. This work provides a clear
      illustration of the utility of solid-state (17)O NMR in quantifying dynamic
      processes occurring in organic solids. Similar studies applied to selectively
      (17)O-labeled biomolecules would appear to be very feasible.

PMID- 22877151
TI  - Coarse-grained molecular simulation of self-assembly for nonionic surfactants on
      graphene nanostructures.
AB  - Self-assembly of amphiphilic molecules on the surfaces of nanoscale materials has
      an important application in a variety of nanotechnology. Here, we report a coarse
      grained molecular dynamics simulation on the structure and morphology of the
      nonionic surfactant, n-alkyl poly(ethylene oxide) (PEO), adsorbed on planar
      graphene nanostructures. The effects of concentration, surfactant structure, and
      size of graphene sheet are explored. Because of the finite dimension effect,
      various morphological hemimicelles can be formed on nanoscale graphene surfaces,
      which is somewhat different from the self-assembly structures on infinite carbon
      surfaces. The aggregate morphology is highly dependent on the concentration, the
      chain lengths, and the size of graphene nanosheets. For the nonionic surfactant,
      the PEO headgroups show strong dispersion interaction with the carbon surface,
      leading to a side edge adsorption behavior. This simulation provides insight into
      the supramolecular self-assembly nanostructures and the adsorption mechanism for
      the nonionic surfactants aggregated on graphene nanostructures, which could be
      exploited to guide fabrication of graphene-based nanocomposites.

PMID- 22877152
TI  - The Farber-Landing lecture: pediatric pathology--the clinician's "open sesame"
      and its importance in pediatric cardiology and cardiovascular surgery.

PMID- 22877153
TI  - Third-trimester genetic amniocentesis in mainland China.

PMID- 22877154
TI  - Modeling the role of environmental variables on the population dynamics of the
      malaria vector Anopheles gambiae sensu stricto.
AB  - BACKGROUND: The impact of weather and climate on malaria transmission has
      attracted considerable attention in recent years, yet uncertainties around future
      disease trends under climate change remain. Mathematical models provide powerful
      tools for addressing such questions and understanding the implications for
      interventions and eradication strategies, but these require realistic modeling of
      the vector population dynamics and its response to environmental variables.
      METHODS: Published and unpublished field and experimental data are used to
      develop new formulations for modeling the relationships between key aspects of
      vector ecology and environmental variables. These relationships are integrated
      within a validated deterministic model of Anopheles gambiae s.s. population
      dynamics to provide a valuable tool for understanding vector response to biotic
      and abiotic variables. RESULTS: A novel, parsimonious framework for assessing the
      effects of rainfall, cloudiness, wind speed, desiccation, temperature, relative
      humidity and density-dependence on vector abundance is developed, allowing ease
      of construction, analysis, and integration into malaria transmission models.
      Model validation shows good agreement with longitudinal vector abundance data
      from Tanzania, suggesting that recent malaria reductions in certain areas of
      Africa could be due to changing environmental conditions affecting vector
      populations. CONCLUSIONS: Mathematical models provide a powerful, explanatory
      means of understanding the role of environmental variables on mosquito
      populations and hence for predicting future malaria transmission under global
      change. The framework developed provides a valuable advance in this respect, but
      also highlights key research gaps that need to be resolved if we are to better
      understand future malaria risk in vulnerable communities.

PMID- 22877155
TI  - Asymmetric Michael addition of ketones to alkylidene malonates and allylidene
      malonates via enamine-metal Lewis acid bifunctional catalysis.
AB  - Novel enamine-metal Lewis acid bifunctional catalysts were successfully applied
      to the asymmetric Michael addition of ketones to alkylidene malonates, offering
      excellent stereoselectivity (up to >99% ee and >99:1 dr). The asymmetric Michael
      addition of ketones to allylidene malonates was also achieved.

PMID- 22877156
TI  - Clinical, epidemiological and molecular features of the HIV-1 subtype C and
      recombinant forms that are circulating in the city of Sao Paulo, Brazil.
AB  - BACKGROUND: The city of Sao Paulo has the highest AIDS case rate, with nearly 60%
      in Brazil. Despite, several studies involving molecular epidemiology, lack of
      data regarding a large cohort study has not been published from this city.
      OBJECTIVES: This study aimed to describe the HIV-1 subtypes, recombinant forms
      and drug resistance mutations, according to subtype, with emphasis on subtype C
      and BC recombinants in the city of Sao Paulo, Brazil. STUDY DESIGN: RNA was
      extracted from the plasma samples of 302 HIV-1-seropositive subjects, of which
      211 were drug-naive and 82 were exposed to ART. HIV-1 partial pol region
      sequences were used in phylogenetic analyses for subtyping and identification of
      drug resistance mutations. The envelope gene of subtype C and BC samples was also
      sequenced. RESULTS: From partial pol gene analyses, 239 samples (79.1%) were
      assigned as subtype B, 23 (7.6%) were F1, 16 (5.3%) were subtype C and 24 (8%)
      were mosaics (3 CRF28/CRF29-like). The subtype C and BC recombinants were mainly
      identified in drug-naive patients (72.7%) and the heterosexual risk exposure
      category (86.3%), whereas for subtype B, these values were 69.9% and 57.3%,
      respectively (p = 0.97 and p = 0.015, respectively). An increasing trend of
      subtype C and BC recombinants was observed (p < 0.01). CONCLUSION: The HIV-1
      subtype C and CRFs seem to have emerged over the last few years in the city of
      Sao Paulo, principally among the heterosexual population. These findings may have
      an impact on preventive measures and vaccine development in Brazil.

PMID- 22877157
TI  - 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and
      selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase AKR1C3.
AB  - A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)
      ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective
      (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both
      breast and prostate cancer. Crystal structure studies showed that the carboxylate
      group occupies the oxyanion hole in the enzyme, while the sulfonamide provides
      the correct twist to allow the dihydroisoquinoline to bind in an adjacent
      hydrophobic pocket. SAR studies around this lead showed that the positioning of
      the carboxylate was critical, although it could be substituted by acid isosteres
      and amides. Small substituents on the dihydroisoquinoline gave improvements in
      potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R
      stereoisomer. The compounds showed good cellular potency, as measured by
      inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a
      broad rank order between enzymic and cellular activity, but amide analogues were
      more effective than predicted by the cellular assay.

PMID- 22877159
TI  - Costs of solar and wind power variability for reducing CO2 emissions.
AB  - We compare the power output from a year of electricity generation data from one
      solar thermal plant, two solar photovoltaic (PV) arrays, and twenty Electric
      Reliability Council of Texas (ERCOT) wind farms. The analysis shows that solar PV
      electricity generation is approximately one hundred times more variable at
      frequencies on the order of 10(-3) Hz than solar thermal electricity generation,
      and the variability of wind generation lies between that of solar PV and solar
      thermal. We calculate the cost of variability of the different solar power
      sources and wind by using the costs of ancillary services and the energy required
      to compensate for its variability and intermittency, and the cost of variability
      per unit of displaced CO(2) emissions. We show the costs of variability are
      highly dependent on both technology type and capacity factor. California
      emissions data were used to calculate the cost of variability per unit of
      displaced CO(2) emissions. Variability cost is greatest for solar PV generation
      at $8-11 per MWh. The cost of variability for solar thermal generation is $5 per
      MWh, while that of wind generation in ERCOT was found to be on average $4 per
      MWh. Variability adds ~$15/tonne CO(2) to the cost of abatement for solar thermal
      power, $25 for wind, and $33-$40 for PV.

PMID- 22877158
TI  - Acceptance patterns and decision-making for human papillomavirus vaccination
      among parents in Vietnam: an in-depth qualitative study post-vaccination.
AB  - BACKGROUND: The GAVI Alliance's decision in late 2011 to invite developing
      countries to apply for funding for human papillomavirus (HPV) vaccine
      introduction underscores the importance of understanding levels of HPV vaccine
      acceptance in developing country settings. In this paper, we present findings
      from qualitative research on parents' rationales for vaccinating or not
      vaccinating their daughters (vaccine acceptance) and their decision-making
      process in the context of an HPV vaccination demonstration project in Vietnam
      (2008-2009). METHODS: We designed a descriptive qualitative study of HPV vaccine
      acceptability among parents of girls eligible for vaccination in four districts
      of two provinces in Vietnama. The study was implemented after each of two years
      of vaccinations was completed. In total, 133 parents participated in 16 focus
      group discussions and 27 semi-structured interviews. RESULTS: Focus group
      discussions and in-depth interviews with parents of girls vaccinated revealed
      that they were generally very supportive of immunization for disease prevention
      and of vaccinating girls against HPV. The involvement of the National Expanded
      Program of Immunization in the demonstration project lent credibility to the HPV
      vaccine, contributing to high levels of acceptance. For parents who declined
      participation, concerns about side effects, the possibility that the vaccine was
      experimental, and the possible impact of the vaccine on future fertility rose to
      the surface. In terms of the decision-making process, many parents exhibited
      'active decision-making,' reaching out to friends, family, and opinion leaders
      for guidance prior to making their decision. CONCLUSION: Vietnam's HPV
      vaccination experience speaks to the importance of close collaboration with the
      government to make the most of high levels of trust, and to reduce suspicions
      about new vaccines that may arise in the context of vaccine introduction in
      developing country settings.

PMID- 22877214
TI  - Is the bioanalytical community ready to revise the use of certain validation
      concepts and nomenclature?

PMID- 22877213
TI  - Automated motif discovery from glycan array data.
AB  - Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans
      on a microarray generates large datasets, making it difficult to identify a
      glycan structural motif or determinant associated with the highest apparent
      binding strength of the GBP. We have developed a computational method, termed
      GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a
      glycan microarray to automatically reveal the glycan structural motifs recognized
      by a GBP. We implemented the software with a web-based graphical interface for
      users to explore and visualize the discovered motifs. The utility of
      GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A,
      and UEA-I. Data from the analyses of the lectins at different protein
      concentrations were processed to rank the glycans based on their relative binding
      strengths. The motifs, defined as glycan substructures that exist in a large
      number of the bound glycans and few non-bound glycans, were then discovered by
      our algorithm and displayed in a web-based graphical user interface (
      http://glycanmotifminer.emory.edu ). The information is used in defining the
      glycan-binding specificity of GBPs. The results were compared to the known glycan
      specificities of these lectins generated by manual methods. A more complex
      analysis was also carried out using glycan microarray data obtained for a
      recombinant form of human galectin-8. Results for all of these lectins show that
      GlycanMotifMiner identified the major motifs known in the literature along with
      some unexpected novel binding motifs.

PMID- 22877212
TI  - Coronary heart disease in primary care: accuracy of medical history and physical
      findings in patients with chest pain--a study protocol for a systematic review
      with individual patient data.
AB  - BACKGROUND: Chest pain is a common complaint in primary care, with coronary heart
      disease (CHD) being the most concerning of many potential causes. Systematic
      reviews on the sensitivity and specificity of symptoms and signs summarize the
      evidence about which of them are most useful in making a diagnosis. Previous meta
      analyses are dominated by studies of patients referred to specialists. Moreover,
      as the analysis is typically based on study-level data, the statistical analyses
      in these reviews are limited while meta-analyses based on individual patient data
      can provide additional information. Our patient-level meta-analysis has three
      unique aims. First, we strive to determine the diagnostic accuracy of symptoms
      and signs for myocardial ischemia in primary care. Second, we investigate
      associations between study- or patient-level characteristics and measures of
      diagnostic accuracy. Third, we aim to validate existing clinical prediction rules
      for diagnosing myocardial ischemia in primary care. This article describes the
      methods of our study and six prospective studies of primary care patients with
      chest pain. Later articles will describe the main results. METHODS/DESIGN: We
      will conduct a systematic review and IPD meta-analysis of studies evaluating the
      diagnostic accuracy of symptoms and signs for diagnosing coronary heart disease
      in primary care. We will perform bivariate analyses to determine the sensitivity,
      specificity and likelihood ratios of individual symptoms and signs and
      multivariate analyses to explore the diagnostic value of an optimal combination
      of all symptoms and signs based on all data of all studies. We will validate
      existing clinical prediction rules from each of the included studies by
      calculating measures of diagnostic accuracy separately by study. DISCUSSION: Our
      study will face several methodological challenges. First, the number of studies
      will be limited. Second, the investigators of original studies defined some
      outcomes and predictors differently. Third, the studies did not collect the same
      standard clinical data set. Fourth, missing data, varying from partly missing to
      fully missing, will have to be dealt with.Despite these limitations, we aim to
      summarize the available evidence regarding the diagnostic accuracy of symptoms
      and signs for diagnosing CHD in patients presenting with chest pain in primary
      care. REVIEW REGISTRATION: Centre for Reviews and Dissemination (University of
      York): CRD42011001170.

PMID- 22877215
TI  - Quantitative/qualitative analysis using LC-HRMS: the fundamental step forward for
      clinical laboratories and clinical practice.

PMID- 22877218
TI  - Recommendations on ISR in multi analyte assays, QA/bioanalytical consultants and
      GCP by Global CRO Council for Bioanalysis (GCC).

PMID- 22877217
TI  - Research Spotlight: The next big thing is actually small.
AB  - Recent developments in materials, surface modifications, separation schemes,
      detection systems and associated instrumentation have allowed significant
      advances in the performance of lab-on-a-chip devices. These devices, also
      referred to as micro total analysis systems (uTAS), offer great versatility, high
      throughput, short analysis time, low cost and, more importantly, performance that
      is comparable to standard bench-top instrumentation. To date, uTAS have
      demonstrated advantages in a significant number of fields including biochemical,
      pharmaceutical, military and environmental. Perhaps most importantly, uTAS
      represent excellent platforms to introduce students to microfabrication and
      nanotechnology, bridging chemistry with other fields, such as engineering and
      biology, enabling the integration of various skills and curricular concepts.
      Considering the advantages of the technology and the potential impact to society,
      our research program aims to address the need for simpler, more affordable,
      faster and portable devices to measure biologically active compounds.
      Specifically, the program is focused on the development and characterization of a
      series of novel strategies towards the realization of integrated microanalytical
      devices. One key aspect of our research projects is that the developed analytical
      strategies must be compatible with each other; therefore, enabling their use in
      integrated devices. The program combines spectroscopy, surface chemistry,
      capillary electrophoresis, electrochemical detection and nanomaterials. This
      article discusses some of the most recent results obtained in two main areas of
      emphasis: capillary electrophoresis, microchip-capillary electrophoresis,
      electrochemical detection and interaction of proteins with nanomaterials.

PMID- 22877219
TI  - Determination of dimethyltryptamine and beta-carbolines (ayahuasca alkaloids) in
      plasma samples by LC-MS/MS.
AB  - BACKGROUND: Ayahuasca is a psychoactive plant beverage originally used by
      indigenous people throughout the Amazon Basin, long before its modern use by
      syncretic religious groups established in Brazil, the USA and European countries.
      The objective of this study was to develop a method for quantification of
      dimethyltryptamine and beta-carbolines in human plasma samples. RESULTS: The
      analytes were extracted by means of C18 cartridges and injected into LC-MS/MS,
      operated in positive ion mode and multiple reaction monitoring. The LOQs obtained
      for all analytes were below 0.5 ng/ml. By using the weighted least squares linear
      regression, the accuracy of the analytical method was improved at the lower end
      of the calibration curve (from 0.5 to 100 ng/ml; r(2)> 0.98). CONCLUSION: The
      method proved to be simple, rapid and useful to estimate administered doses for
      further pharmacological and toxicological investigations of ayahuasca exposure.

PMID- 22877220
TI  - Determination of six pterins in urine by LC-MS/MS.
AB  - BACKGROUND: The present work describes an analytical method for urinary pterins
      by LC-MS/MS, with emphasis on the separation of 6- and 7-positional isomers of
      bio- and neopterins. RESULTS: Urine sample preparation consisted of oxidation by
      MnO(2), filtration and direct dilution in the mobile phase. The method was
      validated in urine spiked at five concentration levels with true triplicates of
      each level. Separation of the pterins, including the positional isomers, was
      achieved by employing a LUNA amino column. Six pterins were quantified (pterin,
      isoxanthopterin, 6-biopterin, 7-biopterin, 6-neopterin, 7-neopterin) and a linear
      behavior was observed; LOD varied from 7 to 360 pg/ml and correlation
      coefficients above 0.98 were obtained for all pterins. In addition, pterin levels
      were evaluated in 41 urine samples of healthy subjects, in ten urine samples of
      patients with classical phenylketonuria (PKU) and in one with atypical PKU.
      CONCLUSION: The proposed method allowed to identify, separate and quantify six
      pterins in urine, using a simple and rapid sample preparation. The atypical PKU
      was unequivocally differentiated from the classical form, demonstrating that this
      method could be very useful for characterization and follow-up of diseases.

PMID- 22877221
TI  - A semi-automated method for the integrated evaluation of half-life and metabolic
      soft spots of discovery compounds.
AB  - BACKGROUND: An integrated method that provides rates of both parent disappearance
      and metabolite formation was developed. RESULTS: Buspirone, mirtazapine and
      verapamil were used as model compounds in developing the method. Incubations were
      carried out on a robotic platform. Qualitative analysis of metabolites in 30 uM
      samples was conducted by data-dependent HPLC-MS/MS on a high-resolution
      instrument. Quantitative analysis of the parent compound and metabolites in 0.5
      uM samples was conducted by full-scan MS(2) with product ion extraction using an
      ion trap mass spectrometer. Data generated for the compounds included half-life
      and intrinsic clearance of the parent molecule, characterization of metabolites
      and relative rates of metabolite formation. A correction factor was used to
      convert MS responses of metabolites in 0.5 uM samples to UV areas in order to
      compare relative metabolite concentrations. CONCLUSION: The approach allows for
      the investigation of a set of six compounds simultaneously, with a turnaround
      time of 1 week or less.

PMID- 22877222
TI  - The use of selected reaction monitoring in quantitative proteomics.
AB  - Selected reaction monitoring (SRM) has a long history of use in the area of
      quantitative MS. In recent years, the approach has seen increased application to
      quantitative proteomics, facilitating multiplexed relative and absolute
      quantification studies in a variety of organisms. This article discusses SRM,
      after introducing the context of quantitative proteomics (specifically primarily
      absolute quantification) where it finds most application, and considers topics
      such as the theory and advantages of SRM, the selection of peptide surrogates for
      protein quantification, the design of optimal SRM co-ordinates and the handling
      of SRM data. A number of published studies are also discussed to demonstrate the
      impact that SRM has had on the field of quantitative proteomics.

PMID- 22877224
TI  - Role of microextraction sampling procedures in forensic toxicology.
AB  - The last two decades have provided analysts with more sensitive technology,
      enabling scientists from all analytical fields to see what they were not able to
      see just a few years ago. This increased sensitivity has allowed drug detection
      at very low concentrations and testing in unconventional samples (e.g., hair,
      oral fluid and sweat), where despite having low analyte concentrations has also
      led to a reduction in sample size. Along with this reduction, and as a result of
      the use of excessive amounts of potentially toxic organic solvents (with the
      subsequent environmental pollution and costs associated with their proper
      disposal), there has been a growing tendency to use miniaturized sampling
      techniques. Those sampling procedures allow reducing organic solvent consumption
      to a minimum and at the same time provide a rapid, simple and cost-effective
      approach. In addition, it is possible to get at least some degree of automation
      when using these techniques, which will enhance sample throughput. Those
      miniaturized sample preparation techniques may be roughly categorized in solid
      phase and liquid-phase microextraction, depending on the nature of the analyte.
      This paper reviews recently published literature on the use of microextraction
      sampling procedures, with a special focus on the field of forensic toxicology.

PMID- 22877226
TI  - Work productivity and healthcare resource utilization outcomes for patients on
      etanercept for moderate-to-severe plaque psoriasis: results from a 1-year,
      multicentre, open-label, single-arm study in a clinical setting.
AB  - BACKGROUND: Data investigating the effect of etanercept on work productivity and
      healthcare resource utilization in Canadian patients in a clinical setting is
      limited. OBJECTIVE: The aim of the study was to describe work productivity and
      healthcare resource utilization in patients with psoriasis prescribed etanercept.
      METHODS: A 12-month, phase IV, non-randomized, multicentre, open-label, single
      arm prospective trial of patients with moderate-to-severe plaque psoriasis was
      conducted between March 2006 and July 2009 in 37 community dermatology practice
      sites across Canada. A total of 246 patients were enrolled. Major eligibility
      criteria: >=18 years of age; diagnosis of moderate-to-severe plaque psoriasis at
      baseline (Physician Global Assessment [PGA] >=3, scale 0-5); able to start
      etanercept therapy as per product monograph. Patients received etanercept
      (Enbrel((r))) 50 mg subcutaneously twice weekly for 3 months, then 50 mg once
      weekly for 9 months. Outcomes were measured by average change and average percent
      change from baseline at months 3, 6, 9 and 12 on the Work Productivity and
      Activity Impairment (WPAI) and Healthcare Resource Utilization (HRU)
      questionnaires. RESULTS: The mean degree of impairment while working +/- standard
      deviation (SD) in the total population decreased from 22.7% +/- 23.2 at baseline
      to 6.6% +/- 14 after 3 months of treatment (p < 0.0001). From baseline to 3
      months, overall work impairment +/- SD decreased from 23.7% +/- 23.7 to 8.3% +/-
      16.5 (p < 0.0001) and mean activity impairment outside the workplace decreased
      from 31.4% +/- 26.4 to 12.9% +/- 22.4 (p < 0.0001). All these improvements were
      sustained to month 12. Other variables that decreased on average from baseline to
      month 3, sustained to month 12, included physician office visits (2.3/month +/-
      3.5 at baseline to 0.6/month +/- 1.0 at month 3; p < 0.0002), hours of assistance
      required of family and friends to assist with psoriasis (1.1 hours/week +/- 2.6
      at baseline to 0.3 hours/week +/- 1.5 at month 3; p = 0.0002) and amount of time
      spent on activities to manage psoriasis (5.5 hours/week +/- 6.2 at baseline to
      1.9 hours/week +/- 3.7 at month 3; p < 0.0001). Also, the amount of out-of-pocket
      expenses to manage psoriasis decreased from $Can94.9/month +/- 331.6 at baseline
      to $Can35.7 +/- 69.1 at month 12 (p = 0.0153). CONCLUSIONS: Use of etanercept in
      Canadian patients in a clinical practice setting correlated with improvement in
      work productivity and reduced HRU after 3 months of treatment, and improvement
      was sustained up to 12 months.

PMID- 22877227
TI  - Stability and permanence in gender- and stage-structured models for the boreal
      toad.
AB  - The boreal toad Bufo boreas boreas, once common in the western USA, is listed as
      an endangered species in Colorado and New Mexico, and protected in Wyoming.
      Populations have dramatically declined due to the presence of the fungal pathogen
      Batrachochytrium dendrobatidis (Bd). A gender- and stage-structured model for the
      boreal toad is formulated which depends on its life cycle and breeding
      strategies. In addition, an epizootic model for the spread of Bd is formulated.
      Analysis of these models provides two thresholds. The first threshold, the basic
      reproduction number for the population, R(0), determines whether the population
      persists and the second threshold, the basic reproduction number for the fungal
      disease, R(F), determines whether the disease persists. If R(0)>1 and R(F)<1,
      then the population becomes disease-free. However, if both thresholds are greater
      than one, the population levels are severely reduced by the fungal pathogen.

PMID- 22877228
TI  - Evaluating the efficacy of antimicrobial cycling programmes and patient isolation
      on dual resistance in hospitals.
AB  - Antibiotic-resistant bacteria cause a number of infections in hospitals and are
      considered a threat to public health. A strategy suggested to curb the
      development of resistant hospital-acquired infections is antimicrobial cycling,
      in which antibiotic classes are alternated over time. This can be compared with a
      mixing programme in which, when given two drugs, half of the physicians prescribe
      one drug over the other. A mathematical model of antimicrobial cycling in a
      hospital population setting is developed to evaluate the efficacy of a cycling
      programme with an emphasis on reducing the emergence and significance of dual
      resistance. The model also considers the effects of physician compliance and
      isolating patients harbouring dual-resistant bacteria. Simulation results show
      that the optimal antimicrobial drug usage programme in hospital populations
      depends upon the type of resistance being targeted for treatment; a cycling
      programme is more effective against dual resistance compared with mixing. Patient
      isolation and high compliance to a cycling programme is also shown to
      dramatically decrease dual resistance in hospitalized populations. Ultimately,
      the exclusive use of antimicrobials in fighting nosocomial infection does not
      solve the problem but just slows down what appears to be a losing battle against
      drug resistance. We hope that this paper serves to instigate discussion on the
      many dimensions of the complex problem of drug resistance in hospital settings.

PMID- 22877223
TI  - Preclinical (1)H-MRS neurochemical profiling in neurological and psychiatric
      disorders.
AB  - The ongoing development of animal models of neurological and psychiatric
      disorders in combination with the development of advanced nuclear magnetic
      resonance (NMR) techniques and instrumentation has led to increased use of in
      vivo proton NMR spectroscopy ((1)H-MRS) for neurochemical analyses. (1)H-MRS is
      one of only a few analytical methods that can assay in vivo and longitudinal
      neurochemical changes associated with neurological and psychiatric diseases, with
      the added advantage of being a technique that can be utilized in both preclinical
      and clinical studies. In this review, recent progress in the use of (1)H-MRS to
      investigate animal models of neurological and psychiatric disorders is summarized
      with examples from the literature and our own work.

PMID- 22877229
TI  - Applications of KAM theory to population dynamics.
AB  - Computer simulations have shown that several classes of population models,
      including the May host-parasitoid model and the Ginzburg-Taneyhill 'maternal
      quality' single species population model, exhibit extremely complicated orbit
      structures. These structures include islands-around-islands, ad infinitum, with
      the smaller islands containing stable periodic points of higher period. We
      identify the mechanism that generates this complexity and we discuss some
      biological implications.

PMID- 22877230
TI  - Stochastic juvenile--adult models with application to a green tree frog
      population.
AB  - We derive several stochastic models from a deterministic population model that
      describes the dynamics of age-structured juveniles coupled with size-structured
      adults. Numerical simulation results of the stochastic models are compared with
      the solution of the deterministic model. These models are then used to understand
      the effect of demographic stochasticity on the dynamics of an urban green tree
      frog (Hyla cinerea) population.

PMID- 22877231
TI  - Glycine-terminated dendritic amphiphiles for nonviral gene delivery.
AB  - Development of nonviral vectors for the successful application of gene therapy
      through siRNA/DNA transfection of cells is still a great challenge in current
      research. (1, 2)  In the present study, we have developed multivalent
      polyglycerol dendron based amphiphiles with well-defined molecular structures
      that express controlled glycine arrays on their surfaces. The structure-activity
      relationships with respect to the siRNA complexation, toxicity, and transfection
      profiles were studied with synthesized amphiphilic polycations. Our findings
      revealed that a second-generation amphiphilic dendrimer (G2-octaamine, 4) that
      has eight amine groups on its surface and a hydrophobic C-18 alkyl chain at the
      core of the dendron, acts as an efficient vector to deliver siRNA and achieve
      potent gene silencing by investigating the knockdown of luciferase and GAPDH gene
      activity in HeLa cells. Interestingly, the amphiphilic vector is nontoxic even at
      higher ratio of N/P 100. To the best of our knowledge this is the first example
      of successful in vitro siRNA transfection using dendritic amphiphiles. We believe
      that this supramolecular complex may serve as a new promising alternative for
      nonviral siRNA delivery systems and will be investigated for in vivo siRNA
      delivery in the future.

PMID- 22877232
TI  - Efficient estimation of MMGBSA-based BEs for DNA and aromatic furan amidino
      derivatives.
AB  - Molecular mechanics with Generalized Born surface area (MMGBSA) based binding
      energies (BEs) derived from the molecular dynamics (MD) trajectories are highly
      reliable and extensively used standards to estimate the strength of interactions
      between ligands and their receptor. MD simulations (5 ns) for 30 aromatic furan
      aminidino derivatives (anti-Pneumocystis carnii agents) have been carried out by
      using Amber program and BEs have been calculated by using Generalized Born (GB)
      method. Based on the generated data, we present a simple and effective method for
      the approximation of BEs without performing MD simulations and MMGBSA
      calculations. Quantum chemical (density functional theory based) and geometrical
      descriptors are used for the prediction of the BE values. All the developed
      models are statistically significant with high values of correlation and cross
      validation coefficients. The prediction ability and effectiveness of the models
      are tested by the division of the data-set into four different training and test
      sets and the average error was only 4-7% (1.56-2.61 kcal/mol) of the actual BEs.

PMID- 22877233
TI  - Bursting the bubble on bacterial biofilms: a flow cell methodology.
AB  - The flow cell biofilm system is an important and widely used tool for the in
      vitro cultivation and evaluation of bacterial biofilms under hydrodynamic
      conditions of flow. This paper provides an introduction to the background and use
      of such systems, accompanied by a detailed guide to the assembly of the apparatus
      including the description of new modifications which enhance its performance. As
      such, this is an essential guide for the novice biofilm researcher as well as
      providing valuable trouble-shooting techniques for even the most experienced
      laboratories. The adoption of a common and reliable methodology amongst
      researchers would enable findings to be shared and replicated amongst the biofilm
      research community, with the overall aim of advancing understanding and
      management of these complex and widespread bacterial communities.

PMID- 22877235
TI  - Mediastinal germ cell tumors in childhood.
AB  - BACKGROUND: Mediastinal germ cell tumors (GCTs) are rare and usually located in
      anterior mediastinum. We aimed to review clinical and pathological
      characteristics of these tumors. PROCEDURE: Between 1973 and 2011, 24 children
      with mediastinal GCTs were diagnosed. Hospital files were reviewed for presenting
      complaints, clinical, radiological and other laboratory data, surgical practices,
      treatments, and outcomes. RESULTS: Median age was 4.5 years (0.2-16)
      (male/female: 10/14). Most common initial complaints were dyspnea, cough,
      anorexia/fatigue, fever, and chest pain. Primary tumors were located in anterior
      mediastinum (n = 22), posterior mediastinum (n = 1), and sternum (n = 1).
      Thirteen of 24 cases had mature teratomas (54.2%); four (16.7%) endodermal sinus
      tumor (EST); four (16.7%) immature teratomas; and one (4.2%) each of embryonal
      carcinoma, teratocarcinoma, and malignant teratoma. Mature teratomas underwent
      only surgical resection and were under follow-up without disease. Four cases with
      ESTs received chemotherapy and radiotherapy (n = 3), three underwent surgical
      resections: three died, one was followed for 284 months in remission. All but one
      immature teratomas were treated with surgery and all were under follow-up without
      disease. Two patients with embryonal carcinoma and malignant teratoma didn't
      undergo surgery; both received chemotherapy and radiotherapy but died with
      disease. The patient with teratocarcinoma was treated with surgery and
      chemotherapy but died with disease. CONCLUSIONS: No adjuvant therapy is needed
      for mature teratomas. Immature teratomas must be under close follow-up for
      recurrences. Prognosis for mediastinal malignant GCTs was poor. These cases need
      intensive chemotherapies and effective local control measures as surgery -/+
      radiotherapy to ensure long-term survival.

PMID- 22877234
TI  - Polymorphisms in genes involved in oxidative stress response in patients with
      sudden sensorineural hearing loss and Meniere's disease in a Japanese population.
AB  - The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and
      Meniere's disease remain unclear. Recently, accumulating evidence has
      demonstrated that oxidative stress is related to the pathology of inner ear
      disease. Because genetic factors may contribute partly to the etiologies of SSNHL
      and Meniere's disease, we investigated the associations between genetic
      polymorphisms located in oxidative stress response genes and susceptibility to
      SSNHL and Meniere's disease. We compared 84 patients affected by SSNHL, 82
      patients affected by Meniere's disease, and 2107 adults (1056 men and 1051 women;
      mean age, 59.2 years; range, 40-79 years) who participated in the National
      Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic
      regression was used to calculate odds ratios for SSNHL and Meniere's disease in
      individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1)
      (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu,
      rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala,
      rs4880), with adjustment for age and gender. No significant differences in the
      distribution of the genotypes at these polymorphisms were observed among
      individuals with SSNHL and Meniere's disease and controls. No significant risk
      for SSNHL and Meniere's disease was observed in the additive genetic model,
      regardless of moderating variables. The C allele of SOD2 (rs4880) was more
      frequent in Meniere's disease cases with a hearing level over 50 dB compared with
      cases with a hearing level below 50 dB, suggesting that this polymorphism is
      associated with progression of a hearing loss in Meniere's disease. In
      conclusion, no significant associations between the polymorphisms of GPX1, PON1,
      PON2, and SOD2 and risk of SSNHL and Meniere's disease were observed in this
      Japanese case-control study.

PMID- 22877236
TI  - Application of matrix-assisted laser desorption/ionization mass spectrometric
      imaging for photolithographic structuring.
AB  - The aim of this contribution is the application of matrix-assisted laser
      desorption/ionization mass spectrometric imaging (MALDI-MSI) in the area of
      photolithographic structuring. As proof of concept, this method was used to image
      an UV exposed negative photoresist layer, which is generally used to manufacture
      printed circuit boards (PCB) for electronic components. The negative photoresist
      layer consisting of the main component novolac, benzophenone as the active
      component, and the solvent tetrahydrofuran was mixed with the matrix dithranol
      and the salt additive LiTFA and spin-coated onto an ITO-conductive glass slide.
      To imprint an image on the created surface, a transparency with a printed wiring
      diagram was placed on top of it and irradiated by UV light for 15 min. The
      inspection of the efficient imprinting of the microstructure onto the photoresist
      layer was performed by MALDI-MSI. This unique application represents a further
      step toward the surface analysis of polymer films by this emerging life science
      imaging technique.

PMID- 22877237
TI  - "A powerful intervention: general practitioners'; use of sickness certification
      in depression".
AB  - BACKGROUND: Depression is frequently cited as the reason for sickness absence,
      and it is estimated that sickness certificates are issued in one third of
      consultations for depression. Previous research has considered GP views of
      sickness certification but not specifically in relation to depression. This study
      aimed to explore GPs views of sickness certification in relation to depression.
      METHODS: A purposive sample of GP practices across Scotland was selected to
      reflect variations in levels of incapacity claimants and antidepressant
      prescribing. Qualitative interviews were carried out between 2008 and 2009.
      RESULTS: A total of 30 GPs were interviewed. A number of common themes emerged
      including the perceived importance of GP advocacy on behalf of their patients,
      the tensions between stakeholders involved in the sickness certification system,
      the need to respond flexibly to patients who present with depression and the
      therapeutic nature of time away from work as well as the benefits of work. GPs
      reported that most patients with depression returned to work after a short period
      of absence and that it was often difficult to predict which patients would
      struggle to return to work. CONCLUSIONS: GPs reported that dealing with sickness
      certification and depression presents distinct challenges. Sickness certificates
      are often viewed as powerful interventions, the effectiveness of time away from
      work for those with depression should be subject to robust enquiry.

PMID- 22877238
TI  - A simple and inexpensive haemozoin-based colorimetric method to evaluate anti
      malarial drug activity.
AB  - BACKGROUND: The spread of drug resistance in malaria parasites and the limited
      number of effective drugs for treatment indicates the need for new anti-malarial
      compounds. Current assays evaluating drugs against Plasmodium falciparum require
      expensive materials and equipment, thus limiting the search for new drugs,
      particularly in developing countries. This study describes an inexpensive
      procedure that is based on the advantage of a positive correlation between the
      haemozoin level of infected erythrocytes and parasite load. METHODS: The
      relationship between parasitaemia and the haemozoin level of infected
      erythrocytes was investigated after converting haemozoin into monomeric haem. The
      50% inhibitory concentration (IC50) values of chloroquine, quinine, artemisinin,
      quinidine and clotrimazole against P. falciparum K1 and 9A strains were
      determined using the novel assay method. RESULTS: The haemozoin of parasites was
      extracted and converted into monomeric haem, allowing the use of a colorimeter to
      efficiently and rapidly measure the growth of the parasites. There was a strong
      and direct linear relationship between the absorbance of haem converted from
      haemozoin and the percentage of the parasite (R2 = 0.9929). Furthermore, the IC50
      values of drugs were within the range of the values previously reported.
      CONCLUSION: The haemozoin-based colorimetric assay can be considered as an
      alternative, simple, robust, inexpensive and convenient method, making it
      applicable in developing countries.

PMID- 22877239
TI  - Curcumin binds to Abeta1-40 peptides and fibrils stronger than ibuprofen and
      naproxen.
AB  - Binding of curcumin, naproxen, and ibuprofen to Abeta1-40 peptide and its fibrils
      is studied by docking method and all-atom molecular dynamics simulations. The
      Gromos96 43a1 force field and simple point charge model of water have been used
      for molecular dynamics simulations. It is shown that if the receptor is a monomer
      then naproxen and ibuprofen are bound to the same place that is different from
      the binding position of curcumin. However all of three ligands have the same
      binding pocket in fibrillar structures. The binding mechanism is studied in
      detail showing that the van der Waals interaction between ligand and receptor
      dominates over the electrostatic interaction. The binding free energies obtained
      by the molecular mechanic-Poisson-Boltzmann surface area method indicate that
      curcumin displays higher binding affinity than nonsteroidal anti-inflammatory
      drugs. Our results are in good agreement with the experiments. 

PMID- 22877240
TI  - Revelation of the ability of Burkholderia sp. USM (JCM 15050) PHA synthase to
      polymerize 4-hydroxybutyrate monomer.
AB  - The nutrition-versatility of Burkholderia sp. strain USM (JCM 15050) has
      initiated the studies on the use of this bacterium for polyhydroxyalkanoate (PHA)
      production. To date, the Burkholderia sp. has been reported to synthesize 3
      hydroxybutyrate, 3-hydroxyvalerate and 3-hydroxy-4-methylvalerate monomers. In
      this study, the PHA biosynthetic genes of this strain were successfully cloned
      and characterized. The PHA biosynthetic cluster of this strain consisted of a PHA
      synthase (phaC), beta-ketothiolase (phaA), acetoacetyl-CoA reductase (phaB) and
      PHA synthesis regulator (phaR). The translated products of these genes revealed
      identities to corresponding proteins of Burkholderia vietnamiensis (99-100 %) and
      Cupriavidus necator H16 (63-89%). Heterologous expression of phaCBs conferred PHA
      synthesis to the PHA-negative Cupriavidus necator PHB-4, confirming that phaCBs
      encoded functionally active protein. PHA synthase activity measurements revealed
      that the crude extracts of C. necator PHB-4 transformant showed higher synthase
      activity (243 U/g) compared to that of wild-types Burkholderia sp. (151 U/g) and
      C. necator H16 (180 U/g). Interestingly, the transformant C. necator PHB-4
      harbouring Burkholderia sp. PHA synthase gene accumulated poly(3-hydroxybutyrate
      co-4-hydroxybutyrate) with 4-hydroxybutyrate monomer as high as up to 87 mol%
      from sodium 4-hydroxybutyrate. The wild type Burkholderia sp. did not have the
      ability to produce this copolymer.

PMID- 22877241
TI  - GWAS-based association between RWDD3 and TECTA variants and paclitaxel induced
      neuropathy could not be confirmed in Scandinavian ovarian cancer patients.

PMID- 22877242
TI  - Intravenous iron supplementation for the treatment of chemotherapy-induced
      anaemia - systematic review and meta-analysis of randomised controlled trials.
AB  - BACKGROUND: Current guidelines are inconclusive regarding intravenous (IV) iron
      for treatment of chemotherapy-induced anaemia (CIA). MATERIAL AND METHODS:
      Systematic review and meta-analysis of randomised controlled trials comparing IV
      iron with no iron or oral iron for treatment of chemotherapy induced anaemia
      (CIA). PRIMARY OUTCOMES: haematopoietic response and red blood cell (RBC)
      transfusion requirements. For dichotomous data, relative risks (RR) with 95%
      confidence intervals (CIs) were estimated and pooled. For continuous data,
      weighted mean differences were calculated. RESULTS: Eleven trials included 1681
      patients, the majority examining the addition of IV iron to erythropoiesis
      stimulating agents (ESA) (1562 patients, 92.9%). IV iron significantly increased
      haematopoietic response rate [RR 1.28 (95% CI 1.125-1.45), seven trials with ESA]
      and decreased the rate of blood transfusions both in trials with ESA [RR 0.76
      (95% CI 0.61-0.95), seven trials] and without ESA [RR 0.52 (95% CI 0.34-0.80)].
      The increase in haematopoietic response rate correlated with total IV iron dose,
      regardless of baseline iron status. Mortality and safety profile was comparable
      between groups. CONCLUSIONS: IV iron added to ESA results in an increase in
      haematopoietic response and reduction in the need for RBC transfusions, with no
      difference in mortality or adverse events.

PMID- 22877243
TI  - Predictors and clinical significance of local recurrence in extremity soft tissue
      sarcoma.
AB  - BACKGROUND: Limb salvage surgery (LSS) has gained widespread acceptance as the
      current treatment for treating extremity soft tissue sarcoma (STS) and has been
      greatly refined since its inception. Combined with improved adjuvant treatment
      modalities, rates of local relapse have greatly decreased. Nonetheless, local
      recurrence still occurs and identifying the cause and the subsequent effects of
      local recurrence can provide valuable insights as LSS continues to evolve.
      METHODS: This retrospective study evaluated 278 patients treated for STS of the
      extremities between 2000 and 2006. Of these, 41 patients developed a local
      recurrence while 247 did not. Tumor characteristics and prognostic outcomes were
      analyzed. Wilcoxon rank sum test and either chi(2) or Fisher's exact was used to
      compare variables. Kaplan Meier and Gray's test for cumulative risk were also
      performed. RESULTS: Patients who had a positive margin were 3.76 times more
      likely to develop local recurrence when compared to those with negative margins.
      This corresponds to a 38% risk of local recurrence if the margins were positive
      after six years vs. 12% if the margins were negative. In patients who underwent a
      re-excision, the presence or absence of residual disease upon re-excision did not
      have any bearing on local recurrence (p = 0.27). In comparing patients with and
      without local recurrence, there was no statistically significant difference in
      the rate and the proportion encountering distant metastasis and death due to
      sarcoma (p > 0.05). CONCLUSIONS: Despite advancements in surgery, radiation and
      imaging, positive margins still occur, and the presence of positive margins
      following definitive treatment continues to remain as a strong predictor for
      local recurrence. While local recurrence represents a negative outcome for a
      patient, its impact on future prognosis is influenced by a variety of factors
      such as time to local recurrence as well as the tumor's inherent biological
      characteristics.

PMID- 22877244
TI  - Low-level HIV infection of hepatocytes.
AB  - BACKGROUND: There are only limited data on whether HIV infection occurs within
      the liver; therefore, we explored early and late stages of the HIV life cycle in
      two hepatocyte cell lines--Huh7.5 and Huh7.5JFH1--as well as in primary human
      hepatocytes. RESULTS: Integrated HIV DNA was detected in Huh7.5 and Huh7.5JFH1
      cells, as well as in primary hepatocytes, and was inhibited by the integrase
      inhibitor raltegravir in a dose-dependent manner. HIV p24 protein was also
      detected in cell culture supernatants at days 1, 3, 5, and 7 post-infection and
      was inhibited by AZT, although levels were modest compared to those in a
      lymphocyte cell line. Culture supernatants from HIV-infected hepatocytes were
      capable of infecting a non-hepatic HIV indicator cell line. CONCLUSIONS: These
      results indicating low-level HIV replication in hepatoctyes in vitro complement
      evidence suggesting that HIV has deleterious effects on the liver in vivo.

PMID- 22877246
TI  - Fetal heart rate in the second stage of labor: recording, reading, interpreting
      and acting.
AB  - Although central to the cardinal movements that lead to the delivery of the
      fetus, the second stage of labor is often neglected from a cultural and clinical
      viewpoint. In this phase, acquisition is more difficult, and reading and
      interpretation may not be the same as in the active first phase. Namely, the most
      relevant findings are the occurrence and depth of bradycardia and its duration.
      This allows the evaluation of fetal heart rate (FHR) even without
      cardiotocographic recording. Instead, FHR can be accurately detected using
      Doppler auscultation, and it is reasonable to speak of "FHR during the second
      stage of labor" instead of "cardiotocography in the second stage of labor."
      Regardless of the cause, including head compression, umbilical cord knots, loops
      around the fetal neck or body, and cord entanglement, the time for intervention
      is often so short that any intervention may be unable to prevent injury.

PMID- 22877245
TI  - Bioisosteric transformations and permutations in the triazolopyrimidine scaffold
      to identify the minimum pharmacophore required for inhibitory activity against
      Plasmodium falciparum dihydroorotate dehydrogenase.
AB  - Plasmodium falciparum causes approximately 1 million deaths annually. However,
      increasing resistance imposes a continuous threat to existing drug therapies. We
      previously reported a number of potent and selective triazolopyrimidine-based
      inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in
      vitro growth with similar activity. Lead optimization of this series led to the
      recent identification of a preclinical candidate, showing good activity against
      P. falciparum in mice. As part of a backup program around this scaffold, we
      explored heteroatom rearrangement and substitution in the triazolopyrimidine ring
      and have identified several other ring configurations that are active as PfDHODH
      inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more
      potently than the triazolopyrimidines depending on the nature of the amino
      aniline substitution. DSM151, the best candidate in this series, binds with 4
      fold better affinity (PfDHODH IC(50) = 0.077 MUM) than the equivalent
      triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei
      model.

PMID- 22877248
TI  - Marked difference in the electronic structure of cyanide-ligated ferric
      protoglobins and myoglobin due to heme ruffling.
AB  - Electron paramagnetic resonance experiments reveal a significant difference
      between the principal g values (and hence ligand-field parameters) of the ferric
      cyanide-ligated form of different variants of the protoglobin of Methanosarcina
      acetivorans (MaPgb) and of horse heart myoglobin (hhMb). The largest principal g
      value of the ferric cyanide-ligated MaPgb variants is found to be significantly
      lower than for any of the other globins reported so far. This is at least
      partially caused by the strong heme distortions as proven by the determination of
      the hyperfine interaction of the heme nitrogens and mesoprotons. Furthermore, the
      experiments confirm recent theoretical predictions [Forti, F.; Boechi, L.,
      Bikiel, D., Marti, M.A.; Nardini, M.; Bolognesi, M.; Viappiani, C.; Estrin, D.;
      Luque, F. J. J. Phys. Chem. B 2011, 115, 13771-13780] that Phe(G8)145 plays a
      crucial role in the ligand modulation in MaPgb. Finally, the influence of the N
      terminal 20 amino-acid chain on the heme pocket in these protoglobins is also
      proven.

PMID- 22877305
TI  - Psychometric testing of the short version of the world health organization
      quality of life (WHOQOL-BREF) questionnaire among pulmonary tuberculosis patients
      in Taiwan.
AB  - BACKGROUND: Studies on the effects of tuberculosis on a patient's quality of life
      (QOL) are scant. The objective of this study was to evaluate the psychometric
      properties of the Taiwan short version of the World Health Organization Quality
      of Life (WHOQOL-BREF) questionnaire using patients with tuberculosis in Taiwan
      and healthy referents. METHODS: The Taiwanese short version of the WHOQOL-BREF
      was administered to patients with tuberculosis undergoing treatment and healthy
      referents from March 2007 to July 2007. Patients with tuberculosis (n = 140) and
      healthy referents (n = 130), matched by age, sex, and ethnicity, agreed to an
      interview. All participants lived in eastern Taiwan. Reliability assessments
      included internal consistency, whereas validity assessments included construct
      validity, convergent validity, and discriminant validity. RESULTS: More than half
      of these patients and referents were men (70.7% and 66.2%, respectively), and
      their average ages were 50.1 and 47.9 years, respectively. Approximately 60% of
      patients and referents were aboriginal Taiwanese (60.7% and 61.1%, respectively).
      The proportion with low socioeconomic status was greater for these patients. The
      internal consistency reliability coefficients were .92 and .93 for the patients
      and healthy referents, respectively. Exploratory factor analysis on the healthy
      referents displayed a 4-domain model, which was compatible with the original
      WHOQOL-BREF 4-domain model. However, for the TB patient group, after deleting 3
      items, both exploratory and confirmatory factor analysis revealed a 6-domain
      model. CONCLUSION: Psychometric evaluation of the Taiwan short version of the
      WHOQOL-BREF indicates that it has adequate reliability for use in research with
      TB patients in Taiwan. However, the factor structure generated from this TB
      patient sample differed from the WHO's original 4-factor model, which raised a
      validity concern to apply the Taiwan short version of the WHOQOL-BREF to
      Taiwanese TB patients. Future research recruiting another sample to revisit this
      validity issue must be conducted to determine the validity of the WHOQOL-BREF TW
      in patients with TB.

PMID- 22877306
TI  - Behavioural and psychological responses of lower educated smokers to the smoke
      free legislation in Dutch hospitality venues: a qualitative study.
AB  - OBJECTIVE: In 2008, smoke-free legislation was implemented in hospitality venues
      (HV) in the Netherlands. We investigated how continuing smokers with a lower
      educational background respond behaviourally and psychologically to the
      legislation and the norm it communicates. DESIGN: In 2010, 18 lower-educated
      daily smokers were interviewed. Transcripts were analysed with MAXQDA software.
      Theories of self-awareness and social in- and exclusion were applied to interpret
      findings. RESULTS: Smokers had become more self-aware and the experience of a
      more negative norm surrounding smoking had made them reevaluate their smoking.
      Smokers had also become more self-aware of their own smoking, both in HV and in
      general. Feelings of increased social exclusion were reported. Participants dealt
      with the increased awareness and feelings of social exclusion in different ways
      depending on their evaluation of the smoking ban, changes in attitude towards own
      smoking, changes in HV patronage and changes in smoking behaviour. CONCLUSION:
      Theories of self-awareness and social in- and exclusion were useful in
      understanding consequences of a HV smoking ban on continuing smokers. Four
      different types of responses were identified, i.e. (1) actively trying to quit,
      (2) socially conscious smoking, (3) feeling victimised and (4) rejecting the
      norm. Implications for future smoke-free legislation are discussed.

PMID- 22877307
TI  - Attenuated protein expression vectors for use in siRNA rescue experiments.
AB  - Transient transfection of small interfering RNA (siRNA) provides a powerful
      approach for studying cellular protein functions, particularly when the target
      protein can be re-expressed from an exogenous siRNA-resistant construct in order
      to rescue the knockdown phenotype, confirm siRNA target specificity, and support
      mutational analyses. Rescue experiments often fail, however, when siRNA-resistant
      constructs are expressed at suboptimal levels. Here, we describe an ensemble of
      mammalian protein expression vectors with CMV promoters of differing strengths.
      Using CHMP2A rescue of HIV-1 budding, we show that these vectors can combine high
      transfection efficiencies with tunable protein expression levels to optimize the
      rescue of cellular phenotypes induced by siRNA transfection.

PMID- 22877308
TI  - Formation of beta-lactoglobulin nanofibrils by microwave heating gives a peptide
      composition different from conventional heating.
AB  - A novel procedure involving microwave heating (MH) at 80  degrees C can be used
      to induce self-assembly of beta-lactoglobulin (beta-lg) into amyloid-like
      nanofibrils at low pH. We examined the self-assembly induced by MH, and evaluated
      structural and compositional differences between MH fibrils and those formed by
      conventional heating (CH). MH significantly accelerated the self-assembly of beta
      lg, resulting in fully developed fibrils in <=2 h. However, longer MH caused
      irreversible disintegration of fibrils. An increase in the fibril yield was
      observed during the storage of the 2 h MH sample, which gave a yield similar to
      that of 16 h CH sample. Fourier transform infrared (FTIR) and circular dichroism
      (CD) spectra suggested that the fibrils formed by the two methods do not show
      significant differences in their secondary structure components. However, they
      exhibited differences in surface hydrophobicity, and mass spectrometry showed
      that the MH fibrils contained larger peptides than CH fibrils, including intact
      beta-lg monomers, providing evidence for a different composition between the MH
      and CH fibrils, in spite of no observed differences in their morphology. We
      suggest MH initially accelerates the self-assembly of beta-lg due to its
      nonthermal effects on unfolding, nucleation, and subsequent stacking of beta
      sheets, rather than promoting partial hydrolysis. Thus, MH fibrils are composed
      of larger peptides, and the observed higher surface hydrophobicity for the MH
      fibrils was attributed to the parts of the larger peptides extending out of the
      core structure of the fibrils.

PMID- 22877309
TI  - Construction and assessment of reaction models of Class I EPSP synthase. Part II:
      investigation of the EPSP ketal.
AB  - Although the proposed mechanisms are reasonable, there are still many questions
      about the 5-enolpyruvyl shikimate-3-phosphate (EPSP) synthase mechanism that are
      difficult to answer by experimental means alone. EPSP synthase is a key enzyme in
      the shikimic acid pathway, which is found only in plants and some micro-organisms
      and is also molecular target of glyphosate, active component of one of the top
      selling herbicides. In the study of reaction mechanism of EPSP synthase, in
      addition to inorganic phosphate and EPSP products, after long time at
      equilibrium, it was shown that a side product is formed, the EPSP ketal. In this
      line, studies using density functional theory (DFT) techniques were performed to
      investigate the reaction mechanism of formation of EPSP and the corresponding
      ketal. Our findings indicate some key amino acid residues in the EPSP synthase
      mechanism and a possible route for the formation of the EPSP ketal.

PMID- 22877310
TI  - Effects of patient factors on noninvasive liver stiffness measurement using
      acoustic radiation force impulse elastography in patients with chronic hepatitis
      C.
AB  - BACKGROUND: Previous research has shown variation in the effects of patient
      factors, including hepatic necroinflammatory activity, on liver stiffness
      measurement (LSM). This prospective study attempts to identify explanatory
      factors for LSM in patients with chronic hepatitis C (CHC) using acoustic
      radiation force impulse (ARFI) technology. METHODS: A cohort of 127 Taiwanese
      patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy.
      This study compares the concurrent diagnostic performances of LSM and FibroTest
      using receiver operating characteristic (ROC) curves. Three multiple linear
      regression models were used to evaluate the significance of concurrent patient
      factors in explaining LSM. RESULTS: To classify METAVIR fibrosis (F) stages, the
      areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI),
      0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI
      LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for
      F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95%
      CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and
      biological covariates, biochemical and histological necroinflammatory factors
      consistently explained LSM. Factors included serum alanine aminotransferase
      (ALT)/upper limit of normal (ULN) categories (model R(2) = 0.661, adjusted R(2) =
      0.629), ActiTest A scores (R(2) = 0.662, adjusted R(2) = 0.636), and METAVIR
      activity (A) grades (R(2) = 0.651, adjusted R(2) = 0.620). METAVIR F stages, body
      mass index, and platelet count were also independently associated with LSM.
      Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A
      grades, explained the false positivity of liver fibrosis staging using ARFI LSM.
      CONCLUSIONS: The degree of hepatic necroinflammatory activity independently and
      significantly exaggerated liver fibrosis evaluation using ARFI LSM. However,
      comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising
      alternative, or adjunctive single indicator, for liver fibrosis evaluation in
      patients with CHC.

PMID- 22877311
TI  - Role of comprehensive geriatric assessment in the management of osteoporotic hip
      fracture in the elderly: an overview.
AB  - PURPOSE: To highlight the advantages of comprehensive geriatric assessment (CGA)
      over usual care in the management of elderly patients with fragility hip
      fractures in terms of reducing the related mortality and disability. METHOD: An
      overview of publications on the topic was conducted using the MEDLINE and EMBASE
      databases. RESULTS: Several models of geriatric and orthopedic comanagement have
      been developed in recent years, all characterized by a variable degree of
      integration, and they have been shown to reduce complications, disability and
      mortality in elderly hip-fracture patients. Preoperatively, CGA should identify
      the comorbidities that need to be treated in view of surgery, so as to reduce the
      related risks. After surgery, CGA should deal with medical complications and
      assure patients an early mobilization in order to reduce short-term mortality and
      contain functional decline. Before discharge, the orthogeriatric team should draw
      up a tailored program to promote the patient's functional recovery and
      satisfactory quality of life, also covering the secondary prevention of fragility
      fractures by improving bone quality and reducing the risk of falls. CONCLUSIONS:
      Fragility hip fractures in the elderly people need to be managed by different
      professionals working in close cooperation and adopting a CGA.

PMID- 22877312
TI  - Phylogenetic relationships among global populations of Pseudomonas syringae pv.
      actinidiae.
AB  - ABSTRACT   Pseudomonas syringae pv. actinidiae, the causal agent of canker in
      kiwifruit (Actinidia spp.) vines, was first detected in Japan in 1984, followed
      by detections in Korea and Italy in the early 1990s. Isolates causing more severe
      disease symptoms have recently been detected in several countries with a wide
      global distribution, including Italy, New Zealand, and China. In order to
      characterize P. syringae pv. actinidiae populations globally, a representative
      set of 40 isolates from New Zealand, Italy, Japan, South Korea, Australia, and
      Chile were selected for extensive genetic analysis. Multilocus sequence analysis
      (MLSA) of housekeeping, type III effector and phytotoxin genes was used to
      elucidate the phylogenetic relationships between P. syringae pv. actinidiae
      isolates worldwide. Four additional isolates, including one from China, for which
      shotgun sequence of the whole genome was available, were included in phylogenetic
      analyses. It is shown that at least four P. syringae pv. actinidiae MLSA groups
      are present globally, and that marker sets with differing evolutionary
      trajectories (conserved housekeeping and rapidly evolving effector genes) readily
      differentiate all four groups. The MLSA group designated here as Psa3 is the
      strain causing secondary symptoms such as formation of cankers, production of
      exudates, and cane and shoot dieback on some kiwifruit orchards in Italy and New
      Zealand. It is shown that isolates from Chile also belong to this MLSA group.
      MLSA group Psa4, detected in isolates collected in New Zealand and Australia, has
      not been previously described. P. syringae pv. actinidiae has an extensive global
      distribution yet the isolates causing widespread losses to the kiwifruit industry
      can all be traced to a single MLSA group, Psa3.

PMID- 22877313
TI  - The mode of host resistance to Plasmopara viticola infection of grapevines.
AB  - ABSTRACT   The resistance and susceptibility of grapevines to downy mildew (DM)
      disease caused by Plasmopara viticola were compared among different
      cultivars/accessions belonging to Vitis vinifera, V. rotundifolia, and 10
      oriental Vitis species. After inoculation with P. viticola pathogen, no symptom
      was found in V. rotundifolia grapevines at all, while oriental species V. davidii
      and V. piasezkii, like V. vinifera, were susceptible to DM disease. The other
      eight oriental Vitis species showed various resistance levels to DM disease.
      Intraspecific resistant variations were also observed in V. amurensis. Microscopy
      studies were conducted on various time courses after pathogen infection on grape
      leaves. P. viticola hyphae were not observed in V. rotundifolia cultivars, while
      symptoms with varying degrees of severity were observed among the Euvitis
      species. In general, the DM resistant oriental species showed a slower
      development of hypha and less formation of haustoria than DM susceptible V.
      vinifera grapevines. Cells with distinctive fluorescence were observed in V.
      rotundifolia and the oriental species V. pseudoreticulata, and callose deposits
      were observed in V. rotundifolia, V. pseudoreticulata, and V. amurensis
      grapevines. Based on the results of morphological observations and microscopy
      studies, we concluded that there were five levels of grapevine resistance to P.
      viticola pathogen: (i) immune, (ii) extremely resistant, (iii) resistant, (iv)
      partly resistant, and (v) susceptible.

PMID- 22877314
TI  - RpfF-dependent regulon of Xylella fastidiosa.
AB  - ABSTRACT   Xylella fastidiosa regulates traits important to both virulence of
      grape as well as colonization of sharpshooter vectors via its production of a
      fatty acid signal molecule known as DSF whose production is dependent on rpfF.
      Although X. fastidiosa rpfF mutants exhibit increased virulence to plants, they
      are unable to be spread from plant to plant by insect vectors. To gain more
      insight into the traits that contribute to these processes, a whole-genome
      Agilent DNA microarray for this species was developed and used to determine the
      RpfF-dependent regulon by transcriptional profiling. In total, 446 protein coding
      genes whose expression was significantly different between the wild type and an
      rpfF mutant (false discovery rate < 0.05) were identified when cells were grown
      in PW liquid medium. Among them, 165 genes were downregulated in the rpfF mutant
      compared with the wild-type strain whereas 281 genes were over-expressed. RpfF
      function was required for regulation of 11 regulatory and sigma factors,
      including rpfE, yybA, PD1177, glnB, rpfG, PD0954, PD0199, PD2050, colR, rpoH, and
      rpoD. In general, RpfF is required for regulation of genes involved in attachment
      and biofilm formation, enhancing expression of hemagglutinin genes hxfA and hxfB,
      and suppressing most type IV pili and gum genes. A large number of other RpfF
      dependent genes that might contribute to virulence or insect colonization were
      also identified such as those encoding hemolysin and colicin V, as well as genes
      with unknown functions.

PMID- 22877315
TI  - Anaesthesia and physiological monitoring during in vivo imaging of laboratory
      rodents: considerations on experimental outcomes and animal welfare.
AB  - The implementation of imaging technologies has dramatically increased the
      efficiency of preclinical studies, enabling a powerful, non-invasive and
      clinically translatable way for monitoring disease progression in real time and
      testing new therapies. The ability to image live animals is one of the most
      important advantages of these technologies. However, this also represents an
      important challenge as, in contrast to human studies, imaging of animals
      generally requires anaesthesia to restrain the animals and their gross motion.
      Anaesthetic agents have a profound effect on the physiology of the animal and may
      thereby confound the image data acquired. It is therefore necessary to select the
      appropriate anaesthetic regime and to implement suitable systems for monitoring
      anaesthetised animals during image acquisition. In addition, repeated anaesthesia
      required for longitudinal studies, the exposure of ionising radiations and the
      use of contrast agents and/or imaging biomarkers may also have consequences on
      the physiology of the animal and its response to anaesthesia, which need to be
      considered while monitoring the animals during imaging studies. We will review
      the anaesthesia protocols and monitoring systems commonly used during imaging of
      laboratory rodents. A variety of imaging modalities are used for imaging rodents,
      including magnetic resonance imaging, computed tomography, positron emission
      tomography, single photon emission computed tomography, high frequency ultrasound
      and optical imaging techniques such as bioluminescence and fluorescence imaging.
      While all these modalities are implemented for non-invasive in vivo imaging,
      there are certain differences in terms of animal handling and preparation, how
      the monitoring systems are implemented and, importantly, how the imaging
      procedures themselves can affect mammalian physiology. The most important and
      critical adverse effects of anaesthetic agents are depression of respiration,
      cardiovascular system disruption and thermoregulation. When anaesthetising
      rodents, one must carefully consider if these adverse effects occur at the
      therapeutic dose required for anaesthesia, if they are likely to affect the image
      acquisitions and, importantly, if they compromise the well-being of the animals.
      We will review how these challenges can be successfully addressed through an
      appropriate understanding of anaesthetic protocols and the implementation of
      adequate physiological monitoring systems.

PMID- 22877316
TI  - Central tendency measure and wavelet transform combined in the non-invasive
      analysis of atrial fibrillation recordings.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common supraventricular
      arrhythmia in the clinical practice, being the subject of intensive research.
      METHODS: The present work introduces two different Wavelet Transform (WT)
      applications to electrocardiogram (ECG) recordings of patients in AF. The first
      one predicts spontaneous termination of paroxysmal AF (PAF), whereas the second
      one deals with the prediction of electrical cardioversion (ECV) outcome in
      persistent AF patients. In both cases, the central tendency measure (CTM) from
      the first differences scatter plot was applied to the AF wavelet decomposition.
      In this way, the wavelet coefficients vector CTM associated to the AF frequency
      scale was used to assess how atrial fibrillatory (f) waves variability can be
      related to AF events. RESULTS: Structural changes into the f waves can be
      assessed by combining WT and CTM to reflect atrial activity organization
      variation. This fact can be used to predict organization-related events in AF. To
      this respect, results in the prediction of PAF termination regarding sensitivity,
      specificity and accuracy were 100%, 91.67% and 96%, respectively. On the other
      hand, for ECV outcome prediction, 82.93% sensitivity, 90.91% specificity and
      85.71% accuracy were obtained. Hence, CTM has reached the highest diagnostic
      ability as a single predictor published to date. CONCLUSIONS: Results suggest
      that CTM can be considered as a promising tool to characterize non-invasive AF
      signals. In this sense, therapeutic interventions for the treatment of paroxysmal
      and persistent AF patients could be improved, thus, avoiding useless procedures
      and minimizing risks.

PMID- 22877318
TI  - Management of adult onset orbital hemangioma by oral propranalol: a case report.
AB  - Adult hemangiomas are usually benign vascular tumors presenting as painless
      progressive proptosis, sometimes accompanied by serious visual loss due to
      compression of the optic nerve. The current treatment modality for these
      hemangiomas is excision through orbitotomy. However, this may be associated with
      potentially serious side effects like injury to optic nerve, double vision,
      squint and ptosis. Many reports have been published demonstrating the impressive
      effect of systemic propranolol in the management of infantile hemangiomas. We
      report the successful use of systemic propranolol in a 56-year-old lady who had
      an extraconal apical orbital hemangioma, compressing the optic nerve. To our
      knowledge, this is the first reported case of adult onset hemangioma, resolving
      almost completely with oral propranolol treatment.

PMID- 22877317
TI  - The efficacies of modified mechanical post conditioning on myocardial protection
      for patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with cardioplegic cardiac
      arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. The
      aim of this study was to investigate whether a modified mechanical post
      conditioning (MMPOC) technique has a myocardial protective effect by enhancing
      early metabolic recovery of the heart following revascularization. METHODS: A
      prospective, randomized trial was conducted at a single-center university
      hospital performing adult cardiac surgery. Seventy-nine adult patients undergoing
      first-time elective isolated multivessel coronary artery bypass grafting were
      prospectively randomized to MMPOC or control group. Anesthetic, cardiopulmonary
      bypass, myocardial protection, and surgical techniques were standardized. The
      post reperfusion cardiac indices, inotrope use and biochemical
      electrocardiographic evidence of myocardial injury were recorded. The incidence
      of postoperative complications was recorded prospectively. RESULTS: Operative
      characteristics, including CPB and aortic cross-clamp time, were similar between
      the two groups (p>0.05). The MMPOC group had lower troponin I and other cardiac
      biomarkers level post CPB and postoperatively, with greater improvement in
      cardiac indices (p<0.001). MMPOC shortened post surgery hospitalization from 9.1
      +/- 2.1 to 7.5 +/- 1.6 days (p<0.001). CONCLUSIONS: MMPOC technique promotes
      early metabolic recovery of the heart during elective CABG, leading to better
      myocardial protection and functional recovery.

PMID- 22877319
TI  - Mechanistic and conformational flexibility of the covalent linkage formed during
      beta-lyase activity on an AP-site: application to hOgg1.
AB  - The beta/delta-lyase activity of bifunctional glycosylases on damaged nucleotides
      in DNA involves the formation of a covalent linkage between the protein (lysine
      or N-terminal proline) and DNA (C1' of the damaged nucleotide). In the present
      study, the conformational and mechanistic flexibility of the cross-link is
      examined. Repair of 8-oxoguanine damage by hOgg1 is considered as a
      representative system, and the glycosylase through beta-lyase steps are
      investigated using density functional theory. (PCM/SMD)-M06-2X/6
      311+G(2df,2p)//PCM-B3LYP/6-31G(d) energetics were determined for eight unique
      mechanisms differing in the conformation of the imine linkage (E/Z), the proton
      (pro-S/R) abstracted during elimination, and whether the ring-opening step is
      base catalyzed. This initial study used a model system limited to the damaged
      nucleoside 3'-monophosphate and a model nucleophile to investigate this series of
      complex reaction steps. The great flexibility exhibited by the linkage and
      clustered beta-elimination energetics indicate sterics will play a large role in
      predicting the preferred lyase mechanism for a given enzyme. The stationary
      points identified herein can be overlaid into a protein structure to assist in
      generating initial guesses for large model systems. By comparing the
      characterized geometries and enzyme active sites, methods for catalysis of the
      various chemical steps can be identified, and these possibilities are discussed
      in detail for hOgg1. Interestingly, the most stable structure on the potential
      energy surface occurs before elimination of the 3'-phosphate. Hydrolysis of the
      protein-DNA cross-link at this point would yield an AP-site, which provides
      support for the recently observed monofunctional activity of hOgg1.

PMID- 22877320
TI  - Effect of resource subsidies on predator-prey population dynamics: a mathematical
      model.
AB  - The influence of a resource subsidy on predator-prey interactions is examined
      using a mathematical model. The model arises from the study of a biological
      system involving arctic foxes (predator), lemmings (prey), and seal carcasses
      (subsidy). In one version of the model, the predator, prey and subsidy all occur
      in the same location; in a second version, the predator moves between two
      patches, one containing only the prey and the other containing only the subsidy.
      Criteria for feasibility and stability of the different equilibrium states are
      studied both analytically and numerically. At small subsidy input rates, there is
      a minimum prey carrying capacity needed to support both predator and prey. At
      intermediate subsidy input rates, the predator and prey can always coexist. At
      high subsidy input rates, the prey cannot persist even at high carrying
      capacities. As predator movement increases, the dynamic stability of the predator
      prey-subsidy interactions also increases.

PMID- 22877321
TI  - Optimization of blood pressure treatment with fixed-combination
      perindopril/amlodipine in patients with arterial hypertension.
AB  - BACKGROUND: Fixed-dose combination treatments using an angiotensin-converting
      enzyme (ACE) inhibitor, such as perindopril, plus a calcium channel blocker
      (CCB), such as amlodipine, have been endorsed by guidelines because they improve
      blood pressure control and cardiovascular outcomes in hypertensive patients,
      while being well tolerated and well adhered to by patients. OBJECTIVE: This study
      aimed to assess the blood pressure-lowering effects of fixed-combination
      perindopril/amlodipine in patients previously treated with an ACE inhibitor
      and/or a CCB. METHODS: This was a prospective, real-life, open-label,
      longitudinal, phase IV study conducted in 223 outpatient medical centres across
      Slovakia. 2132 previously treated patients whose hypertension was insufficiently
      controlled at baseline or who tolerated treatment poorly were included. Patients
      were treated for 3 months with fixed-combination perindopril/amlodipine 5 mg/5
      mg, 5 mg/10 mg, 10 mg/5 mg and 10 mg/10 mg. The main outcome measure was a
      reduction in mean systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) and achievement of blood pressure targets (SBP/DBP <140/90 mmHg or <130/80
      mmHg for patients with type 2 diabetes mellitus or high cardiovascular risk).
      RESULTS: After 3 months of treatment, mean +/- SD SBP/DBP had decreased from
      158.5 +/- 17.5/93.6 +/- 9.8 mmHg to 132.9 +/- 10.6/80.7 +/- 6.2 mmHg (p <
      0.0001). In patients with grade 3 hypertension, mean +/- SD changes from baseline
      in SBP/DBP were -45.4 +/- 16.4/-20.0 +/- 11.5 mmHg after 3 months (p < 0.0001).
      Blood pressure targets were reached by 74% of the overall patient population, 84%
      of patients with grade 1 hypertension, and 52% of difficult-to-treat patients
      with grade 3 hypertension. This treatment was associated with a 58% reduction in
      the number of patients with amlodipine-related ankle oedema compared with
      baseline. CONCLUSION: Fixed-combination perindopril/amlodipine was well tolerated
      and resulted in statistically significant and clinically meaningful decreases in
      blood pressure.

PMID- 22877322
TI  - Azilsartan medoxomil: a review of its use in hypertension.
AB  - Azilsartan medoxomil (Edarbi(r); IprezivTM) is an orally administered angiotensin
      II receptor type 1 antagonist (blocker) used in the treatment of adults with
      essential hypertension. This article reviews data on the clinical efficacy and
      tolerability of azilsartan medoxomil in adults with essential hypertension and
      provides a summary of its pharmacological properties. Azilsartan medoxomil is a
      prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after oral
      administration to the bioactive moiety azilsartan, before systemic absorption.
      Azilsartan medoxomil produces antihypertensive effects by selectively blocking
      the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor, thereby
      antagonizing the pressor response activity of angiotensin II. In vitro,
      azilsartan produced greater and more sustained AT(1) receptor binding/blockade
      activity than several comparator angiotensin II receptor antagonists. Azilsartan
      medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the
      drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1)
      receptor blockade). In adults with essential hypertension, azilsartan medoxomil
      20, 40 or 80 mg effectively reduced BP over a 24-hour period with once-daily
      administration in three major, randomized, controlled trials in which the primary
      endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6
      (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two
      6-week trials, azilsartan medoxomil showed dose-dependent efficacy over all
      evaluated dosages and was more effective than placebo in lowering SBP. At the
      maximum approved dosage of 80 mg once daily, azilsartan medoxomil was
      significantly more effective than maximum dosages of olmesartan medoxomil (40 mg
      once daily) or valsartan (320 mg once daily), based on primary endpoint
      assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP)
      measurements were also generally greater with azilsartan medoxomil 80 mg once
      daily than with the comparator drugs in these 6-week studies. Over a longer
      treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering
      efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater
      with azilsartan medoxomil 40 or 80 mg once daily than with valsartan 320 mg once
      daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by
      ABPM were also significantly greater with azilsartan medoxomil 40 or 80 mg once
      daily than with valsartan. Azilsartan medoxomil was generally well tolerated,
      with a tolerability profile similar to that of placebo in the 6-week trials.
      Across the three major trials, headache and dizziness were among the most common
      adverse events. Overall, rates of treatment discontinuation as a result of
      adverse events were low in the 6-week and 24-week trials. In conclusion, once
      daily azilsartan medoxomil effectively lowers BP in adults with essential
      hypertension and has shown better antihypertensive efficacy than maximum
      therapeutic dosages of olmesartan medoxomil or valsartan in major trials of up to
      24 weeks' duration. Azilsartan medoxomil is generally well tolerated and the low
      rates of discontinuation due to adverse events suggest that patients are likely
      to persist with long-term treatment. Azilsartan medoxomil is therefore a useful
      and attractive new option for lowering BP in patients with essential
      hypertension, particularly for those not able to tolerate other antihypertensive
      drugs. Further studies are required to evaluate the effects of azilsartan
      medoxomil on cardiovascular morbidity and mortality.

PMID- 22877323
TI  - Intravenous busulfan: a guide to its use as conditioning treatment before
      transplantation of haematopoietic progenitor cells.
AB  - With intravenous administration of busulfan (Busilvex(r)), the therapeutic range
      of the drug is achieved in more paediatric patients than after oral busulfan
      administration. In clinical trials in paediatric and adult patients, intravenous
      busulfan-based preconditioning treatment regimen prior to haematopoietic
      progenitor cell transplantation (HPCT) provided high rates of engraftment, low
      transplant-related mortality rates and good overall survival and progression-free
      survival outcomes. Intravenous busulfan was considered to have an acceptable
      tolerability profile.

PMID- 22877353
TI  - Synthesis, structure, and paramagnetism of manganese(II) iminophosphate
      complexes.
AB  - The coordination chemistry of the bidentate bis(imino)bis(amino)phosphate ligands
      [Me(3)SiN?P{NR}{N(H)R}(2)](-), where R = n-propyl is [L(1)H(2)](-), R =
      cyclohexyl is [L(2)H(2)](-), and R = tert-butyl is [L(3)H(2)](-), with
      manganese(II), is described. The bis(imino)bis(amino)phosphate-manganese(II)
      complexes [(eta(5)-Cp)Mn(MU-L(1)H(2))](2) (1), [Mn(L(2)H(2))(2)].THF (2.THF), and
      [(eta(5)-Cp)Mn(L(3)H(2))] (3) were synthesized by monodeprotonation of the
      respective pro-ligands by manganocene, Cp(2)Mn. The molecular structures of 1-3
      reveal that the steric demands of the ligand N-substituents play a dominant role
      in determining the aggregation state and overall composition of the manganese(II)
      complexes. The coordination geometries of the Mn(II) centers are six-coordinate
      pseudotetrahedral in 1, four-coordinate distorted tetrahedral in 2, and five
      coordinate in 3, resulting in formal valence electron counts of 17, 13, and 15,
      respectively. EPR studies of 1-3 at Q-band reveal high-spin manganese(II) (S =
      5/2) in each case. In the EPR spectrum of 1, no evidence of intramolecular
      magnetic exchange was found. The relative magnitudes of the axial zero-field
      splitting parameter, D, in 2 and 3 are consistent with the symmetry of the
      manganese environment, which are D(2d) in 2 and C(2v) in 3.

PMID- 22877354
TI  - Waist circumference a good indicator of future risk for type 2 diabetes and
      cardiovascular disease.
AB  - BACKGROUND: Abdominal obesity is a more important risk factor than overall
      obesity in predicting the development of type 2 diabetes and cardiovascular
      disease. From a preventive and public health point of view it is crucial that
      risk factors are identified at an early stage, in order to change and modify
      behaviour and lifestyle in high risk individuals. METHODS: Data from a community
      based study was used to assess the risk for type 2 diabetes, cardiovascular
      disease and prevalence of metabolic syndrome in middle-aged men. In order to
      identify those with increased risk for type 2 diabetes and/or cardiovascular
      disease sensitivity and specificity analysis were performed, including
      calculation of positive and negative predictive values, and corresponding 95% CI
      for eleven different cut-off points, with 1 cm intervals (92 to 102 cm), for
      waist circumference. RESULTS: A waist circumference >=94 cm in middle-aged men,
      identified those with increased risk for type 2 diabetes and/or for
      cardiovascular disease with a sensitivity of 84.4% (95% CI 76.4% to 90.0%), and a
      specificity of 78.2% (95% CI 68.4% to 85.5%). The positive predictive value was
      82.9% (95% CI 74.8% to 88.8%), and negative predictive value 80.0%, respectively
      (95% CI 70.3% to 87.1%). CONCLUSIONS: Measurement of waist circumference in
      middle-aged men is a reliable test to identify individuals at increased risk for
      type 2 diabetes and cardiovascular disease. This measurement should be used more
      frequently in daily practice in primary care in order to identify individuals at
      risk and when planning health counselling and interventions.

PMID- 22877356
TI  - Moving beyond the medical model to enhance primary care.

PMID- 22877355
TI  - Targeted analyte detection by standard addition improves detection limits in
      matrix-assisted laser desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool
      for fast and accurate determination of many molecules. However, the detector
      sensitivity and chemical noise compromise the detection of many invaluable low
      abundance molecules from biological and clinical samples. To challenge this
      limitation, we developed a targeted analyte detection (TAD) technique. In TAD,
      the target analyte is selectively elevated by spiking a known amount of that
      analyte into the sample, thereby raising its concentration above the noise level,
      where we take advantage of the improved sensitivity to detect the presence of the
      endogenous analyte in the sample. We assessed TAD on three peptides in simple and
      complex background solutions with various exogenous analyte concentrations in two
      MALDI matrices. TAD successfully improved the limit of detection (LOD) of target
      analytes when the target peptides were added to the sample in a concentration
      close to optimum concentration. The optimum exogenous concentration was estimated
      through a quantitative method to be approximately equal to the original LOD for
      each target. Also, we showed that TAD could achieve LOD improvements on an
      average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a
      straightforward assay to improve the LOD of generic target analytes without the
      need for costly hardware modifications.

PMID- 22877357
TI  - CCA advocacy steps up as policy makers ponder care coordination for dual
      eligibles.

PMID- 22877358
TI  - Chiroptical spectroscopy of natural products: avoiding the aggregation effects of
      chiral carboxylic acids.
AB  - Determination of the absolute configurations and predominant conformations of
      chiral natural products, occurring as carboxylic acids, using chiroptical
      spectroscopic methods becomes challenging due to the formation of solute
      aggregates (in the form of dimers, etc.) and/or solute-solvent complexes
      resulting from intermolecular hydrogen bonding with solvent. A hypothesis that
      such aggregation effects can be avoided by using corresponding sodium salts or
      acid anhydrides for chiroptical spectroscopic measurements has been tested. For
      this purpose, vibrational circular dichroism, electronic circular dichroism, and
      optical rotatory dispersion spectra for disodium salts of two natural products,
      hibiscus acid and garcinia acid, and the anhydride of acetylated garcinia acid
      have been measured. These experimental spectra are analyzed in combination with
      quantum chemical calculations of corresponding spectra. The spectral analysis for
      sodium salts and anhydride turned out to be simpler, suggesting that the
      conversion of carboxylic acids to corresponding salts or anhydride can be
      advantageous for the application of chiroptical spectroscopy.

PMID- 22877359
TI  - A population-based exposure assessment of risk factors associated with
      gastrointestinal pathogens: a Campylobacter study.
AB  - A questionnaire survey was undertaken to determine the exposure of a study
      population to campylobacteriosis source risk factors (environmental, water, food)
      and results were stratified by age, population density and deprivation. Data were
      gathered using an exposure assessment carried out by telephone in the Grampian
      region of Scotland. Univariate analysis showed that children aged 5-14 years,
      living in low population density (0-44.4 persons/km2) and affluent areas had
      elevated exposure to environmental and water risk factors. Multivariate logistic
      regression analysis revealed that younger age groups and lower population density
      were significant indicators for most environmental risk factors. The results
      compared to reported disease incidence in Grampian showed that greater exposure
      to risk factors does not necessarily coincide with greater disease incidence for
      age groups, particularly for the 0-4 years age group. Further research is
      required to explain the relationship between exposure and disease incidence.

PMID- 22877360
TI  - Spatial access to residential care resources in Beijing, China.
AB  - BACKGROUND: As the population is ageing rapidly in Beijing, the residential care
      sector is in a fast expansion process with the support of the municipal
      government. Understanding spatial accessibility to residential care resources by
      older people supports the need for rational allocation of care resources in
      future planning. METHODS: Based on population data and data on residential care
      resources, this study uses two Geographic Information System (GIS) based methods-
      shortest path analysis and a two-step floating catchment area (2SFCA) method to
      analyse spatial accessibility to residential care resources. RESULTS: Spatial
      accessibility varies as the methods and considered factors change. When only time
      distance is considered, residential care resources are more accessible in the
      central city than in suburban and exurban areas. If care resources are considered
      in addition to time distance, spatial accessibility is relatively poor in the
      central city compared to the northeast to southeast side of the suburban and
      exurban areas. The resources in the northwest to southwest side of the city are
      the least accessible, even though several hotspots of residential care resources
      are located in these areas. CONCLUSIONS: For policy making, it may require
      combining various methods for a comprehensive analysis. The methods used in this
      study provide tools for identifying underserved areas in order to improve equity
      in access to and efficiency in allocation of residential care resources in future
      planning.

PMID- 22877361
TI  - Fast and selective room-temperature ammonia sensors using silver nanocrystal
      functionalized carbon nanotubes.
AB  - We report a selective, room-temperature NH(3) gas-sensing platform with enhanced
      sensitivity, superfast response and recovery, and good stability, using Ag
      nanocrystal-functionalized multiwalled carbon nanotubes (Ag NC-MWCNTs). Ag NCs
      were synthesized by a simple mini-arc plasma method and directly assembled on
      MWCNTs using an electrostatic force-directed assembly process. The nanotubes were
      assembled onto gold electrodes with both ends in Ohmic contact. The addition of
      Ag NCs on MWCNTs resulted in dramatically improved sensitivity toward NH(3). Upon
      exposure to 1% NH(3) at room temperature, Ag NC-MWCNTs showed enhanced
      sensitivity (~9%), very fast response (~7 s), and full recovery within several
      minutes in air. Through density functional theory calculations, we found that the
      fully oxidized Ag surface plays a critical role in the sensor response. Ammonia
      molecules are adsorbed at Ag hollow sites on the AgO surface with H pointing
      toward Ag. A net charge transfer from NH(3) to the Ag NC-MWCNTs hybrid leads to
      the conductance change in the hybrid.

PMID- 22877362
TI  - Condensed matter theory of dipolar quantum gases.

PMID- 22877363
TI  - Management of floppy eyelid associated with Down's syndrome: a case report.
AB  - PURPOSE: To report a case of floppy eyelid associated with Down's syndrome in a 2
      year-old child. CASE REPORT: A 2-year-old child associated with Down's syndrome
      presented with a history of eversion of both upper lids during sleep and while
      crying since birth. There was no history of sleep apnea and no mechanical stimuli
      over eyelids. Examination under anesthesia revealed gross laxity with thick and
      rubbery tarsi in both the upper and lower lids. Vascularized corneal scar was
      present in both eyes. The laxity in the upper eyelids was corrected by pentagonal
      wedge resection and in the lower lids by lateral tarsal sling. No recurrence was
      observed up to 6-month follow-up. CONCLUSION: Although floppy eyelid is more
      common in middle-aged obese patients, it should be carefully looked for children
      particularly while dealing with Down's syndrome.

PMID- 22877364
TI  - New bactericidal surgical suture coating.
AB  - This paper demonstrates the effectiveness of a new antimicrobial suture coating.
      An amphiphilic polymer, poly[(aminoethyl methacrylate)-co-(butyl methacrylate)]
      (PAMBM), inspired by antimicrobial peptides, was bactericidal against  S. aureus 
      in time-kill experiments. PAMBM was then evaluated in a variety of polymer blends
      using the Japanese Industrial Standard (JIS) method and showed excellent
      antimicrobial activity at a low concentration (0.5 wt %). Using a similar
      antimicrobial coating formula to commercial Vicryl Plus sutures, disk samples of
      the coating material containing PAMBM effectively killed bacteria (98% reduction
      at 0.75 wt %). Triclosan, the active ingredient in Vicryl Plus coatings, did not
      kill the bacteria. Further Kirby-Bauer assays of these disk samples showed an
      increasing zone of inhibition with increasing concentration of PAMBM. Finally,
      the PAMBM-containing coating was applied to sutures, and the morphology of the
      coating surface was characterized by SEM, along with Vicryl and uncoated sutures.
      The PAMBM-containing sutures killed bacteria more effectively (3 log(10)
      reduction at 2.4 wt %) than Vicryl Plus sutures (0.5 log(10) reduction).

PMID- 22877365
TI  - The effects of template rigidity and amino acid type on heterogeneous calcium
      phosphate mineralization by langmuir films of amphiphilic and acidic beta-sheet
      peptides.
AB  - Calcium-phosphate mineralization was monitored in systems composed of designed
      amphiphilic and acidic beta-sheet-forming peptides, namely Pro-Phe-(Asp-Phe)(5)
      Pro (PFD-5), Pro-Phe-(Glu-Phe)(5)-Pro (PFE-5) and Pro-Glu-(Phe-PSer)(4)-Phe-Glu
      Pro (PPS). The three peptides differ solely in terms of their hydrophilic amino
      acids and therefore, serve as good model for assessment of the effect of the
      anionic amino acid type on mineralization within the context of the beta-sheet
      structure. Monolayers of the peptides were deposited over simulated body solution
      (SBF(1.5)), and the effect of the adsorbing minerals over time was detected by
      Langmuir isotherm measurements, grazing incidence X-ray diffraction (GIXD) and
      Brewster angle microscopy (BAM). The results provide insight into mineralized
      film morphology and peptide lattice behavior during mineralization. The rigidity
      of the peptide template, along with the type of amino acid side chain, were found
      to significantly affect mineralization morphology and peptide structure. The
      results will contribute to a better understanding of calcium-phosphate
      mineralization in nature and in the context of biomaterials for applications in
      bone tissue regeneration.

PMID- 22877366
TI  - Exploring the mechanism of a regulatory SNP of KLK3 by molecular dynamics
      simulation.
AB  - The SNP -158G>A of KLK3 has been validated as a regulatory SNP (rSNP) by
      molecular biology assays, but the mechanism of how it affects the binding of an
      androgen receptor (AR) homodimer with DNA is unclear. In the current study,
      molecular dynamics simulation was adopted to explain its inner cause. Based on a
      recent review), three types of intermolecular forces were analyzed, and the
      differences among them were compared between complexes containing -158 A:T and 
      158 G:C. Extra hydrophobic contacts caused by the methyl group on the mutated
      thymine were the most crucial factor to the regulatory effect of this rSNP.
      Further analysis concerning the relative motion of the two recognition helixes of
      the AR homodimer indicated that the hydrophobic interactions between the
      recognition helix B and the major groove containing -158 A:T changed that helix's
      motion greatly from swaying in a plane at free state to vibrating slightly around
      an equilibrium position. A relatively full explanation on the occurrence of rSNP 
      158G>A is presented here.

PMID- 22877412
TI  - Birth weight and obesity risk at first grade of high school in a non-concurrent
      cohort of Chilean children.
AB  - OBJECTIVE: To determine the association of birth weight with obesity risk at
      first grade of high school in Chilean children after accounting for potential
      confounding factors. DESIGN: National non-concurrent cohort of newborns.
      Sociodemographic information, height, weight and anthropometric measurements at
      first grade of high school were analysed. Birth weight was classified as
      macrosomia (>=4000 g), by gestational age and by ponderal index. The relationship
      between birth weight and obesity at first grade of high school (BMI >= 95th
      percentile of the US Centers for Disease Control and Prevention's reference) was
      assessed using logistic regression models adjusted for sociodemographic
      information at delivery. SETTING: First grade of public high school of low and
      middle socio-economic status in the whole country (about 77 % of Chilean children
      in this age group). SUBJECTS: Newborns (n 119 070) and the same number of high
      school students. RESULTS: A positive relationship of high ponderal index (OR =
      1.86, 95 % CI 1.69, 2.03), birth weight >=4000 g (OR = 1.66, 95 % CI 1.54, 1.78)
      and large for gestational age (OR = 1.69, 95 % CI 1.58, 1.81) with obesity at
      adolescence (P < 0.001) was found. Macrosomic children had a higher risk of being
      obese at first grade of high school after controlling for prenatal confounding
      variables (OR = 1.63, 95 % CI 1.52, 1.76; P < 0.001). CONCLUSIONS: A direct
      relationship between high birth weight and obesity at first grade of high school
      was observed in this group of Chilean children. The results highlight the
      significance of birth weight as a simple tool to be used as an indicator of
      obesity risk for children by health-care providers.

PMID- 22877413
TI  - Analgesic effects of a standardized bioflavonoid composition from Scutellaria
      baicalensis and Acacia catechu.
AB  - Anti-inflammatory properties of both baicalin and catechins have been widely
      reported. However, the reports of analgesic effects of baicalin and catechins are
      limited. Three commonly used pain-related animal models were employed to evaluate
      the analgesic activity of UP446, a standardized bioflavonoid composition of
      baicalin and catechins. Carrageenan-induced paw edema, formalin test, and
      abdominal constriction assays were used to evaluate antinociceptive activity of
      150 mg/kg or 100 mg/kg oral doses of UP446. Ibuprofen was used as a reference
      compound in each test. Pretreatment of carrageenan-induced hyperalgesic animals
      with UP446 at 150 mg/kg oral dosage reduced the hypersensitivity of pain by
      39.5%. Similarly, a single dose of UP446, given orally at 100 mg/kg, exhibited
      58% and 71.9% inhibition in pain sensitivity compared to vehicle-treated control
      in writhing and formalin tests, respectively. These findings suggest that the
      standardized anti-inflammatory bioflavonoid composition, UP446, could also be
      employed to inhibit nociception.

PMID- 22877414
TI  - Weight growth of triplet infants from birth to twelve years of age.
AB  - We analyzed the characteristics associated with the growth in weight of Japanese
      triplets from birth to 12 years of age. The study included 376 mothers and their
      1,128 triplet children, who were born between 1978 and 2006. Data were collected
      through a mailed questionnaire sent to the mothers asking for information
      recorded in medical records. For these births, data on triplets' weight growth,
      gestational age, sex, parity, maternal age at delivery, maternal height, and
      maternal body mass index were obtained from records in the Maternal and Child
      Health Handbooks and records in the school where children receive health check
      ups. The weight deficit of the triplets compared to the general population of
      Japan remained between 10% and 17% until 12 years of age. Moreover, at 12 years
      of age, the differences of weight between the general population and triplets
      were approximately -4.75 kg for boys and -6.00 kg for girls. Very low birth
      weight had the strongest contribution to body weight until 8 years of age. After
      8 years of age, maternal body mass index was a significant factor affecting the
      weight of triplets until 12 years of age.

PMID- 22877415
TI  - Social and behavioral characteristics of gharwalis who operate brothels in the
      Ganga-Jamuna area of Nagpur, India.
AB  - Nagpur is an industrial hub in Maharashtra, a state in Central India that has the
      second highest HIV prevalence in the country. Approximately 3000 brothel-based
      female sex workers (FSWs) are estimated to be working in Nagpur's Ganga-Jamuna
      red light district. The extent to which brothel madams, known as gharwalis,
      support HIV/STI prevention for FSWs has not been examined. The present study
      sought to identify personal, social, and behavioral characteristics of gharwalis
      in Nagpur as well as enhance our understanding of the gharwali's role in shaping
      the sexual practices of brothel-based FSWs. Thirty gharwalis participated in a
      survey that covered personal, social, behavioral, and environmental
      characteristics. Respondents ranged in age from 29 to 50 years (M = 38.9) and had
      worked as a gharwali for an average of 5.3 years; 80% had no formal education,
      43% had never married, and 30% were divorced or separated, and 93% earned money
      from their own sex work. Gharwalis managed an average of 4.2 FSWs (range 2-10).
      Overall, gharwalis reported positive attitudes toward condoms, promoted use of
      condoms by their FSWs with clients, taught FSWs how to use condoms, knew where to
      obtain condoms for free, and required HIV testing for their FSWs; however, levels
      of HIV prevention knowledge were low. Gharwalis also reported providing a range
      of support services to FSWs who lived in their brothels, including shelter,
      protection from drunk and aggressive clients and police, emotional support,
      caring and love, and health care. These data suggest the feasibility of involving
      gharwalis in brothel-based HIV prevention programs.

PMID- 22877417
TI  - Naphthalene and anthracene cobaltates(1-): useful storable sources of an atomic
      cobalt anion.
AB  - Reductions of CoBr(2) or cobaltocene by 3 equiv of  potassium anthracene radical
      anion in tetrahydrofuran (THF) afford 60-80% yields of bis(anthracene)cobaltate(1
      ) (1), of interest as a readily accessible and quite labile source of spin-paired
      atomic Co(-). Although the unsolvated potassium salt of 1 is thermally unstable
      at 20  degrees C, the [K(18-crown-6)(THF)(2)](+) salt of 1 functions as a useful
      storable crystalline reagent for Co(-) in several reactions. Previously known
      classic cobaltates, [CoL(4)](-), for L = 1/2 (1,3-butadiene) (2), PF(3) (3), and
      P(OiPr)(3) (5), were obtained directly from 1 and structurally characterized for
      the first time. Anion 3 is noteworthy because it appears to possess the shortest
      known Co-P distance, av = 2.012(4) A. Although the naphthalene analogue of 1 is
      not yet available as a pure substance, low-temperature reductions of CoBr(2) or
      cobaltocene by  naphthalene radical anion in the presence of 1,5-cyclooctadiene
      (COD) afford variable yields (80-90% from CoCp(2)) of
      (naphthalene)(COD)cobaltate(1-) (10). Ready displacement of naphthalene in 10 by
      L = 1,3-butadiene, 2,2'-bipyridine, and COD occurs to give good yields of the
      respective [Co(L)(COD)](-), all of which have been structurally characterized.
      Both ligands in 10 are displaced by tert-butylisocyanide to afford
      [Co(CNtBu)(4)](-) (16), the first isolable and structurally characterized
      homoleptic alkylisocyanometalate. The molecular structure of 16 shows
      unprecedented bending of the isocyanides, av C-N-C = 137(2) degrees , for
      homoleptic isocyanide complexes.

PMID- 22877416
TI  - Older adults' home- and community-based care service use and residential
      transitions: a longitudinal study.
AB  - BACKGROUND: As Home-and Community-Based Services (HCBS), such as skilled nursing
      services or personal care services, have become increasingly available, it has
      become clear that older adults transit through different residential statuses
      over time. Older adults may transit through different residential statuses as the
      various services meet their needs. The purpose of this exploratory study was to
      better understand the interplay between community-dwelling older adults' use of
      home- and community-based services and their residential transitions. METHODS:
      The study compared HCBS service-use patterns and residential transitions of 3,085
      older adults from the Second Longitudinal Study of Aging. Based on older adults'
      residential status at the three follow-up interviews, four residential
      transitions were tracked: (1) Community-Community-Community (CCC: Resided in
      community during the entire study period); (2) Community-Institution-Community
      (CIC: Resided in community at T1, had lived in an institution at some time
      between T1 and T2, then had returned to community by T3); (3) Community-Community
      Institution (CCI: Resided in community between at T1, and betweenT1 and T2,
      including at T2, but had used institutional services between T2 and T3); (4)
      Community-Institution-Institution (CII: Resided in community at T1 but in an
      institution at some time between T1 and T2, and at some time between T2 and T3.).
      RESULTS: Older adults' use of nondiscretionary and discretionary services
      differed significantly among the four groups, and the patterns of HCBS use among
      these groups were also different. Older adults' use of nondiscretionary services,
      such as skilled nursing care, may help them to return to communities from
      institutions. Personal care services (PCS) and senior center services may be the
      key to either support elders to stay in communities longer or help elders to
      return to their communities from institutions. Different combinations of PCS with
      other services, such as senior center services or meal services, were associated
      with different directions in residential transition, such as CIC and CII
      respectively. CONCLUSIONS: Older adults' differing HCBS use patterns may be the
      key to explaining older adults' transitions. Attention to older adults' HCBS use
      patterns is recommended for future practice. However, this was an exploratory
      study and the analyses cannot establish causal relationships.

PMID- 22877418
TI  - The Cedar Project: high incidence of HCV infections in a longitudinal study of
      young Aboriginal people who use drugs in two Canadian cities.
AB  - BACKGROUND: Factors associated with HCV incidence among young Aboriginal people
      in Canada are still not well understood. We sought to estimate time to HCV
      infection and the relative hazard of risk factors associated HCV infection among
      young Aboriginal people who use injection drugs in two Canadian cities. METHODS:
      The Cedar Project is a prospective cohort study involving young Aboriginal people
      in Vancouver and Prince George, British Columbia, who use illicit drugs.
      Participants' venous blood samples were drawn and tested for HCV antibodies.
      Analysis was restricted to participants who use used injection drugs at enrolment
      or any of follow up visit. Cox proportional hazards regression was used to
      identify independent predictors of time to HCV seroconversion. RESULTS: In total,
      45 out of 148 participants seroconverted over the study period. Incidence of HCV
      infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3,
      46.1) among participants who reported using injection drugs for two years or
      less, 14.4 per 100 person-years (95% CI: 7.7, 28.9) among participants who had
      been using injection drugs for between two and five years, and 5.1 per 100 person
      years (95% CI: 2.6,10.9) among participants who had been using injection drugs
      for over five years. Independent associations with HCV seroconversion were
      involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR):
      1.59; 95% CI: 1.05, 2.42) compared to no involvement, having been using injection
      drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94) and for between two
      and five years (AHR: 2.12; 95%CI: 0.94, 4.77) compared to over five years, daily
      cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05) compared
      to less than daily, and sharing intravenous needles in the last six months (AHR:
      2.56; 95% CI: 1.47, 4.49) compared to not sharing. CONCLUSIONS: This study
      contributes to the limited body of research addressing HCV infection among
      Aboriginal people in Canada. The HCV incidence rate among Cedar Project
      participants who were new initiates of injection drug use underscores an urgent
      need for HCV and injection prevention and safety strategies aimed at supporting
      young people surviving injection drug use and sex work in both cities. Young
      people must be afforded the opportunity to provide leadership and input in the
      development of prevention programming.

PMID- 22877419
TI  - A bottom-up approach to estimating cost elements of REDD+ pilot projects in
      Tanzania.
AB  - BACKGROUND: Several previous global REDD+ cost studies have been conducted,
      demonstrating that payments for maintaining forest carbon stocks have significant
      potential to be a cost-effective mechanism for climate change mitigation. These
      studies have mostly followed highly aggregated top-down approaches without
      estimating the full range of REDD+ costs elements, thus underestimating the
      actual costs of REDD+. Based on three REDD+ pilot projects in Tanzania,
      representing an area of 327,825 ha, this study explicitly adopts a bottom-up
      approach to data assessment. By estimating opportunity, implementation,
      transaction and institutional costs of REDD+ we develop a practical and
      replicable methodological framework to consistently assess REDD+ cost elements.
      RESULTS: Based on historical land use change patterns, current region-specific
      economic conditions and carbon stocks, project-specific opportunity costs ranged
      between US$ -7.8 and 28.8 tCOxxxx for deforestation and forest degradation
      drivers such as agriculture, fuel wood production, unsustainable timber
      extraction and pasture expansion. The mean opportunity costs for the three
      projects ranged between US$ 10.1 - 12.5 tCO2. Implementation costs comprised
      between 89% and 95% of total project costs (excluding opportunity costs) ranging
      between US$ 4.5 - 12.2 tCO2 for a period of 30 years. Transaction costs for
      measurement, reporting, verification (MRV), and other carbon market related
      compliance costs comprised a minor share, between US$ 0.21 - 1.46 tCO2.
      Similarly, the institutional costs comprised around 1% of total REDD+ costs in a
      range of US$ 0.06 - 0.11 tCO2. CONCLUSIONS: The use of bottom-up approaches to
      estimate REDD+ economics by considering regional variations in economic
      conditions and carbon stocks has been shown to be an appropriate approach to
      provide policy and decision-makers robust economic information on REDD+. The
      assessment of opportunity costs is a crucial first step to provide information on
      the economic baseline situation of deforestation and forest degradation agents
      and on the economic incentives required to halt unsustainable land use. Since
      performance based REDD+ carbon payments decrease over time (as deforestation
      rates drop and for each saved ha of forest payments occur once), investments in
      REDD+ implementation have a crucial role in triggering sustainable land use
      systems by investing in the underlying assets and the generation of sustainable
      revenue streams to compensate for opportunity costs of land use change. With a
      potential increase in the land value due to effective REDD+ investments,
      expenditures in an enabling institutional environment for REDD+ policies are
      crucial to avoid higher deforestation pressure on natural forests.

PMID- 22877420
TI  - The role of adaptations in two-strain competition for sylvatic Trypanosoma cruzi
      transmission.
AB  - This study presents a continuous-time model for the sylvatic transmission
      dynamics of two strains of Trypanosoma cruzi enzootic in North America, in order
      to study the role that adaptations of each strain to distinct modes of
      transmission (classical stercorarian transmission on the one hand, and vertical
      and oral transmission on the other) may play in the competition between the two
      strains. A deterministic model incorporating contact process saturation predicts
      competitive exclusion, and reproductive numbers for the infection provide a
      framework for evaluating the competition in terms of adaptive trade-off between
      distinct transmission modes. Results highlight the importance of oral
      transmission in mediating the competition between horizontal (stercorarian) and
      vertical transmission; its presence as a competing contact process advantages
      vertical transmission even without adaptation to oral transmission, but such
      adaptation appears necessary to explain the persistence of (vertically-adapted)
      T. cruzi IV in raccoons and woodrats in the southeastern United States.

PMID- 22877421
TI  - Reshaping nanocrystals for tunable plasmonic substrates.
AB  - Plasmonic nanostructures with tunable optical properties and their designed
      spatial arrangements can facilitate a variety of application ranging from
      plasmonics to biosensors with unprecedented sensitivity. Here we describe a
      facile and versatile method for fabricating tunable plasmonic substrates based on
      the reshaping of metal nanocrystals. Anisotropic etching and redeposition of Ag
      atoms mediated by halide ions transformed Ag nanoprisms deposited on two- or
      three-dimensional surfaces or in solution into nanostructures with an oblate
      spheroidal shape, and corresponding localized surface plasmon resonances features
      could be tuned. The reshaping nanocrystal strategy can even facilitate the
      preparation of new classes of plasmonic substrates with gradient or patterned
      plasmonic properties, which cannot be realized easily using existing lithographic
      techniques. The substrates with gradient plasmonic properties can serve as
      platforms for tunable surface-enhanced Raman scattering.

PMID- 22877423
TI  - Meta-analysis of three randomized trials and nine observational studies comparing
      drug-eluting stents versus coronary artery bypass grafting for unprotected left
      main coronary artery disease.
AB  - Clinical outcomes for unprotected left main coronary artery (ULMCA) disease
      between coronary artery bypass grafting (CABG) and drug-eluting stents (DESs)
      remain controversial. We aimed to compare the safety and efficacy of percutaneous
      coronary intervention (PCI) using DESs with CABG in patients with ULMCA disease.
      Databases were searched for clinical studies that reported outcomes after PCI
      with DESs and CABG for treatment of ULMCA disease. End points of this meta
      analysis were mortality; composite of death, myocardial infarction (MI), or
      stroke; and target vessel revascularization at 1-year follow-up. Pooled effects
      were calculated using fixed-effects model (Mantel-Haenszel method) or random
      effects models (Dersimonian-Laird method). Twelve clinical studies (3 randomized
      trials and 9 observational studies) with 5,079 patients were involved in this
      study. At 1-year follow-up, there were trends toward lower risk of death (odds
      ratio [OR] 0.68, 95% confidence interval [CI] 0.45 to 1.02) and the composite end
      point of death, MI, or stroke (OR 0.70, 95% CI 0.49 to 1.00) in the DES group
      compared to the CABG group. However, target vessel revascularization was
      significantly higher in the DES group compared to the CABG group (OR 3.52, 95% CI
      2.72 to 4.56). In conclusion, PCI with DESs is associated with favorable outcomes
      for mortality; composite end point of death, MI, or stroke; and a higher risk of
      target vessel revascularization compared to CABG in patients with ULMCA disease.

PMID- 22877422
TI  - The correlates of benefit from neoadjuvant chemotherapy before surgery in non
      small-cell lung cancer: a metaregression analysis.
AB  - BACKGROUND: Although neoadjuvant chemotherapy (NCT) is widely used, it is not
      clear which subgroup of locally advanced non-small-cell lung cancer (NSCLC)
      patients should be treated with this approach, and if a particular benefit
      associated with NCT exists. In this study, we aimed to investigate the potential
      correlates of benefit from NCT in patients with NSCLC. METHODS: All randomized
      clinical trials (RCTs) utilizing a NCT arm (without radiotherapy) versus a
      control arm before surgery were included for metaregression analysis. All
      regression analyses were weighed for trial size. Separate analyses were conducted
      for trials recruiting patients with different stages of disease. Previously
      published measures of treatment efficacy were used for the purpose of this study,
      regardless of being published in full text or abstract form. RESULTS: A total of
      14 RCTs, consisting of 3,615 patients, were selected. Histology, stage, various
      characteristics of the NCT protocol, and different trial features including trial
      quality score were not associated with the benefit of NCT. However, in trials of
      stage 3 disease only, there was a greater benefit in terms of reduction in
      mortality from NCT, if protocols with three chemotherapeutics were used (B = 
      0.18, t = -5.25, P = 0.006). CONCLUSIONS: We think that patients with stage 3
      NSCLC are served better with NCT before surgery if protocols with three
      chemotherapy agents or equally effective combinations are used. In addition, the
      effect of neoadjuvant chemotherapy is consistent with regard to disease and
      patient characteristics. This finding should be tested in future RCTs or
      individual patient data meta-analyses.

PMID- 22877424
TI  - Relation of statin nonadherence and treatment intensification.
AB  - Failure to intensify medication and failure to adhere to medication have been
      shown to contribute to suboptimal low-density lipoprotein cholesterol goal
      attainment. To examine whether nonadherence to statins in 126,903 patients on
      stable statin therapy is associated with subsequent treatment intensification, we
      conducted a retrospective analysis using an integrated pharmacy and medical
      claims database. Pharmacy claims were analyzed to determine whether nonadherence,
      as measured by proportion of days covered on statins <80%, was associated with
      intensification of statin treatment over a 360-day follow-up. Of 11,361 patients
      who had treatment intensification, 44% were previously nonadherent to statins.
      Patients whose treatment was intensified had slightly lower adherence to statin
      therapy than those without intensification (76% vs 78%, p <0.0001) and were more
      likely to be nonadherent as defined by proportion of days covered <80% (44% vs
      37%, p <0.0001). After controlling for confounding factors, patients nonadherent
      to statins were 30% more likely to have treatment intensification compared to
      adherent patients (odds ratio 1.30, 95% confidence interval 1.25 to 1.36). In
      addition, patients with statin intensification were more likely to be younger,
      women, and have coronary artery disease, diabetes, hypertension, dyslipidemia,
      stroke, peripheral arterial disease, heart failure, or depression. Primary care
      physicians were more likely to escalate therapy than cardiologists. In
      conclusion, nearly 1/2 of patients with therapy escalation were nonadherent to
      statins. Clinicians should inquire about adherence and consider adherence before
      escalating statin therapy.

PMID- 22877425
TI  - Pathophysiology of osteoporosis: new mechanistic insights.
AB  - Understanding of the pathophysiology of osteoporosis has evolved to include
      compromised bone strength and skeletal fragility caused by several factors: (1)
      defects in microarchitecture of trabeculae, (2) defective intrinsic material
      properties of bone tissue, (3) defective repair of microdamage from normal daily
      activities, and (4) excessive bone remodeling rates. These factors occur in the
      context of age-related bone loss. Clinical studies of estrogen deprivation,
      antiresorptives, mechanical loading, and disuse have helped further knowledge of
      the factors affecting bone quality and the mechanisms that underlie them. This
      progress has led to several new drug targets in the treatment of osteoporosis.

PMID- 22877426
TI  - Bisphosphonates in the treatment of osteoporosis.
AB  - Bisphosphonates are widely used in the treatment of osteoporosis to reduce
      fracture risk. Because of their long retention time in bone and uncommon side
      effects, questions have been raised about the optimal duration of therapy.
      Potential side effects appear to be rare and may not be causally related.
      Although there is no strong science to guide "drug holidays," there appears to be
      some lingering antifracture benefit when treatment is stopped, so some time off
      treatment should be offered to most patients on long-term bisphosphonate therapy.
      For most patients with osteoporosis, the benefits of treatment outweigh the
      risks.

PMID- 22877427
TI  - Anabolic therapies for osteoporosis.
AB  - As the first FDA-approved anabolic agent for osteoporosis, teriparatide has
      proven effective for people at highest risk of fracture, despite limitations of
      expense, route of delivery, and length of treatment. Available data show that
      combination therapy with teriparatide and antiresorptive agents does not offer a
      therapeutic advantage. However, treatment with an antiresorptive agent after
      teriparatide discontinuation is essential to prevent the ensuing bone loss.
      Although pretreatment with bisphosphonates may somewhat attenuate the anabolic
      effect of teriparatide, significant gains in bone mineral density are still
      achieved and prior bisphosphonate use should not dissuade clinicians from using
      teriparatide in select patients.

PMID- 22877428
TI  - Calcium metabolism and correcting calcium deficiencies.
AB  - Calcium is the most abundant cation in the human body, of which approximately 99%
      occurs in bone, contributing to its rigidity and strength. Bone also functions as
      a reservoir of Ca for its role in multiple physiologic and biochemical processes.
      This article aims to provide a thorough understanding of the absorptive
      mechanisms and factors affecting these processes to enable one to better
      appreciate an individual's Ca needs, and to provide a rationale for correcting Ca
      deficiencies. An overview of Ca requirements and suggested dosing regimens is
      presented, with discussion of various Ca preparations and potential toxicities of
      Ca treatment.

PMID- 22877429
TI  - How vitamin D works on bone.
AB  - Vitamin D is important for the normal development and maintenance of bone. The
      elucidation of the vitamin D activation pathway and the cloning of the vitamin D
      receptor have advanced our understanding of the actions of vitamin D on bone. The
      preponderance of evidence indicates that 1,25(OH)2D3 enhances bone mineralization
      through its effects to promote calcium and phosphate absorption. Although
      1,25(OH)2D3 stimulates bone resorption in vitro, treatment in vivo can prevent
      bone loss and fracture through several potential mechanisms. The development of
      vitamin D analogues has provided new therapeutic options for increasing bone
      mineral density and reducing fractures.

PMID- 22877430
TI  - Extraskeletal effects of vitamin D.
AB  - The presence of vitamin D receptors in diverse tissues like immune cells, beta
      cells in the pancreas, and cardiac myocytes has prompted research to evaluate the
      impact of vitamin D deficiency on the occurrence of immune diseases, diabetes,
      and cardiovascular disease (CVD). The expression of receptors not only in normal
      cells, but also in cancer cells including breast, prostate, and colon cancer
      cells has moreover opened the path to therapeutic exploitation of vitamin D or
      its metabolites and hypocalcemic structural analogues as pharmaceutical tools in
      the fight against chronic non-communicable diseases like diabetes, CVD, and
      cancer.

PMID- 22877431
TI  - Glucocorticoid-induced osteoporosis and osteonecrosis.
AB  - Glucocorticoid administration is the most common cause of secondary osteoporosis
      and the leading cause of nontraumatic osteonecrosis. In patients receiving long
      term therapy, glucocorticoids induce fractures in 30% to 50% and osteonecrosis in
      9% to 40%. This article reviews glucocorticoid-induced osteoporosis and
      osteonecrosis, addressing the risk factors, pathogenesis, evaluation, treatment,
      and uncertainties in the clinical management of these disorders.

PMID- 22877432
TI  - Unrecognized and unappreciated secondary causes of osteoporosis.
AB  - There are a substantial number of secondary causes of osteoporosis that can be
      identified through appropriate evaluation. Unrecognized celiac disease,
      Monoclonal gamopathy of undetermined significance (MGUS), impaired renal
      function, diabetes mellitus, and renal tubular acidosis are just a few of the
      more common secondary causes of osteoporosis. Through targeted laboratory tests,
      many secondary causes of osteoporosis can be identified.

PMID- 22877433
TI  - Male osteoporosis.
AB  - Osteoporosis is now recognized as a major threat to health in aging men.
      Morbidity and mortality, particularly following hip fracture, are substantial.
      Although trabecular bone loss starts in early adulthood, loss of cortical bone
      only seems to occur from midlife onwards. Declining bioavailable estradiol levels
      plays an integral role in male age-associated bone loss. Both pharmacologic and
      supportive care interventions are important for optimal care in men at an
      increased fracture risk.

PMID- 22877434
TI  - Combination anabolic and antiresorptive therapy for osteoporosis.
AB  - Osteoanabolic agents directly stimulate bone formation to improve bone mass and
      skeletal microarchitecture. At present, parathyroid hormone (PTH), in the form of
      the full-length molecule (PTH(1-84)) and its fully active, but truncated amino
      terminal fragment, PTH(1-34) (teriparatide), are the only medications that belong
      to the osteoanabolic class. It is appealing to consider simultaneous combination
      therapy with antiresorptive and osteoanabolic drugs as potentially more
      beneficial than monotherapy with either class, given that their mechanisms of
      action differ. This review focuses on the research that has been conducted on
      combination therapy with PTH and an antiresorptive drug.

PMID- 22877435
TI  - Future directions in osteoporosis therapeutics.
AB  - Future directions in osteoporosis treatment will include development of
      medications with increasingly precise mechanistic targets, including the RANK
      ligand pathway, cathepsin K inhibition, and Wnt signaling manipulation. More
      gains are likely with anabolics and newer antiresorptives that cause little or no
      suppression of formation. Optimal treatment of osteoporosis may require
      coordination of anabolic and antiresorptive treatment, following stimulation of
      bone formation with consolidation and long-term maintenance. Some well
      established drugs may be useful in such regimens. We can also anticipate emphasis
      on cost containment using currently available drugs, especially as they become
      generic. Effective implementation and treatment continuity will be important
      themes.

PMID- 22877436
TI  - Osteoporosis. Foreword.

PMID- 22877437
TI  - Osteoporosis. Preface.

PMID- 22877497
TI  - New approach via gene knockout and single-step chemical reaction for the
      synthesis of isotopically labeled fusarin c as an internal standard for the
      analysis of this fusarium mycotoxin in food and feed samples.
AB  - The gold standard for quantitation of contaminants with high-performance liquid
      chromatography tandem mass spectrometry (HPLC-MS/MS) is the use of isotopically
      labeled standards. Herein, we report a new strategy for the synthesis of
      isotopically labeled 21-d3-fusarin C via a genetically modified Fusarium strain,
      followed by a one-step derivatization reaction. Fusarin C is a Fusarium
      mycotoxin, which is mutagenic after metabolic activation. Its occurrence has been
      demonstrated recently in corn-based samples, but up to now, little is known about
      the contamination of other grain samples. To collect further data, the
      quantitation method was enhanced by application of the 21-d3-fusarin C and the
      use of a QTRAP 5500 mass spectrometer. This new method has a limit of detection
      (LOD) of 1 MUg/kg, a limit of quantitation (LOQ) of 4 MUg/kg, and a recovery rate
      of 99%. A total of 21 corn samples and 13 grain samples were analyzed, with
      resulting fusarin C levels varying from not detectable to 24.7 MUg/kg. 

PMID- 22877498
TI  - Extreme water-related weather events and waterborne disease.
AB  - Global climate change is expected to affect the frequency, intensity and duration
      of extreme water-related weather events such as excessive precipitation, floods,
      and drought. We conducted a systematic review to examine waterborne outbreaks
      following such events and explored their distribution between the different types
      of extreme water-related weather events. Four medical and meteorological
      databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting
      system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne
      outbreaks involving extreme water-related weather events were identified and
      included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most
      common events preceding outbreaks associated with extreme weather and were
      reported in 55.2% and 52.9% of accounts, respectively. The most common pathogens
      reported in these outbreaks were Vibrio spp. (21.6%) and Leptospira spp. (12.7%).
      Outbreaks following extreme water-related weather events were often the result of
      contamination of the drinking-water supply (53.7%). Differences in reporting of
      outbreaks were seen between the scientific literature and ProMED. Extreme water
      related weather events represent a risk to public health in both developed and
      developing countries, but impact will be disproportionate and likely to compound
      existing health disparities.

PMID- 22877499
TI  - External validity in healthy public policy: application of the RE-AIM tool to the
      field of housing improvement.
AB  - BACKGROUND: Researchers and publishers have called for improved reporting of
      external validity items and for testing of existing tools designed to assess
      reporting of items relevant to external validity. Few tools are available and
      most of this work has been done within the field of health promotion. METHODS: We
      tested a tool assessing reporting of external validity items which was developed
      by Green & Glasgow on 39 studies assessing the health impacts of housing
      improvement. The tool was adapted to the topic area and criteria were developed
      to define the level of reporting, e.g. "some extent". Each study was assessed by
      two reviewers. RESULTS: The tool was applicable to the studies but some items
      required considerable editing to facilitate agreement between the two reviewers.
      Levels of reporting of the 17 external validity items were low (mean 6). The most
      commonly reported items related to outcomes. Details of the intervention were
      poorly reported. Study characteristics were not associated with variation in
      reporting. CONCLUSIONS: The Green & Glasgow tool was useful to assess reporting
      of external validity items but required tailoring to the topic area. In some
      public health evaluations the hypothesised impact is dependent on the
      intervention effecting change, e.g. improving socio-economic conditions. In such
      studies data confirming the function of the intervention may be as important as
      details of the components and implementation of the intervention.

PMID- 22877501
TI  - Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: a
      preclinical study.
AB  - BACKGROUND: The treatment options for patients requiring repair of a long segment
      of the urethra are limited by the availability of autologous tissues. We
      previously reported that acellular collagen-based tubularized constructs seeded
      with cells are able to repair small urethral defects in a rabbit model.
      OBJECTIVE: We explored the feasibility of engineering clinically relevant long
      urethras for surgical reconstruction in a canine preclinical model. DESIGN,
      SETTING, AND PARTICIPANTS: Autologous bladder epithelial and smooth muscle cells
      from 15 male dogs were grown and seeded onto preconfigured collagen-based tubular
      matrices (6 cm in length). The perineal urethral segment was removed in 21 male
      dogs. Urethroplasties were performed with tubularized collagen scaffolds seeded
      with cells in 15 animals. Tubularized constructs without cells were implanted in
      six animals. Serial urethrography and three-dimensional computed tomography (CT)
      scans were performed pre- and postoperatively at 1, 3, 6, and 12 mo. The animals
      were euthanized at their predetermined time points (three animals at 1 mo, and
      four at 3, 6, and 12 mo) for analyses. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Statistical analysis of CT imaging and histology was not needed.
      RESULTS AND LIMITATIONS: CT urethrograms showed wide-caliber urethras without
      strictures in animals implanted with cell-seeded matrices. The urethral segments
      replaced with acellular scaffolds collapsed. Gross examination of the urethral
      implants seeded with cells showed normal-appearing tissue without evidence of
      fibrosis. Histologically, an epithelial cell layer surrounded by muscle fiber
      bundles was observed on the cell-seeded constructs, and cellular organization
      increased over time. The epithelial and smooth muscle phenotypes were confirmed
      using antibodies to pancytokeratins AE1/AE3 and smooth muscle-specific desmin.
      Formation of an epithelial cell layer occurred in the unseeded constructs, but
      few muscle fibers formed. CONCLUSIONS: Cell-seeded tubularized collagen scaffolds
      can be used to repair long urethral defects, whereas scaffolds without cells lead
      to poor tissue development and strictures. This study demonstrates that long
      tissue-engineered tubularized urethral segments may be used for urethroplasty in
      patients.

PMID- 22877502
TI  - Epidemiology and risk factors of urothelial bladder cancer.
AB  - CONTEXT: Urothelial bladder cancer (UBC) is a disease of significant morbidity
      and mortality. It is important to understand the risk factors of this disease.
      OBJECTIVE: To describe the incidence, prevalence, and mortality of UBC and to
      review and interpret the current evidence on and impact of the related risk
      factors. EVIDENCE ACQUISITION: A literature search in English was performed using
      PubMed. Relevant papers on the epidemiology of UBC were selected. EVIDENCE
      SYNTHESIS: UBC is the 7th most common cancer worldwide in men and the 17th most
      common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are
      noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed
      with new cases and 38 200 patients in the European Union and 17 000 US patients
      die from UBC. Smoking is the most common risk factor and accounts for
      approximately half of all UBCs. Occupational exposure to aromatic amines and
      polycyclic aromatic hydrocarbons are other important risk factors. The impact of
      diet and environmental pollution is less evident. Increasing evidence suggests a
      significant influence of genetic predisposition on incidence. CONCLUSIONS: UBC is
      a frequently occurring malignancy with a significant impact on public health and
      will remain so because of the high prevalence of smoking. The importance of
      primary prevention must be stressed, and smoking cessation programs need to be
      encouraged and supported.

PMID- 22877503
TI  - Extranodal extension is a powerful prognostic factor in bladder cancer patients
      with lymph node metastasis.
AB  - BACKGROUND: Lymph node metastasis (LNM) is the most powerful pathologic predictor
      of disease recurrence after radical cystectomy (RC). However, the outcomes of
      patients with LNM are highly variable. OBJECTIVE: To assess the prognostic value
      of extranodal extension (ENE) and other lymph node (LN) parameters. DESIGN,
      SETTING, AND PARTICIPANTS: A retrospective analysis of 748 patients with
      urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy
      without neoadjuvant therapy at 10 European and North American centers (median
      follow-up: 27 mo). INTERVENTION: All subjects underwent RC and bilateral pelvic
      lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Each LNM was
      microscopically evaluated for the presence of ENE. The number of LNs removed,
      number of positive LNs, and LN density were recorded and calculated. Univariable
      and multivariable analyses addressed time to disease recurrence and cancer
      specific mortality after RC. RESULTS AND LIMITATIONS: A total of 375 patients
      (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN
      density were 15, 2, and 15, respectively. The rate of ENE increased with
      advancing pT stage (p<0.001). In multivariable Cox regression analyses that
      adjusted for the effects of established clinicopathologic features and LN
      parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89;
      95% confidence interval [CI], 1.55-2.31; p<0.001) and cancer-specific mortality
      (HR: 1.90; 95% CI, 1.52-2.37; p<0.001). The addition of ENE to a multivariable
      model that included pT stage, tumor grade, age, gender, lymphovascular invasion,
      surgical margin status, LN density, number of LNs removed, number of positive
      LNs, and adjuvant chemotherapy improved predictive accuracy for disease
      recurrence and cancer-specific mortality from 70.3% to 77.8% (p<0.001) and from
      71.8% to 77.8% (p=0.007), respectively. The main limitation of the study is its
      retrospective nature. CONCLUSIONS: ENE is an independent predictor of both cancer
      recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of
      ENE status could help with patient counseling, clinical decision making regarding
      inclusion in clinical trials of adjuvant therapy, and tailored follow-up
      scheduling after RC.

PMID- 22877504
TI  - One-pot synthesis of dendritic gold nanostructures in aqueous solutions of
      quaternary ammonium cationic surfactants: effects of the head group and
      hydrocarbon chain length.
AB  - Hierarchical, three-fold symmetrical dendritic gold was prepared in an aqueous
      solution of the quaternary ammonium cationic surfactant dodecyltrimethylammonium
      bromide (DTAB). Similar surfactants with different head groups and hydrocarbon
      chain lengths were also used for comparison. Two-fold and one-fold symmetrical
      dendritic gold nanostructures were obtained in N-dodecyl-N-methylpyrrolidinium
      bromide (C(12)-MPB) and dodecyltriethylammonium bromide (DTEAB) aqueous
      solutions, respectively. Longer hydrocarbon chain lengths were unfavorable for
      the formation of dendritic nanostructures. The interaction energies between the
      individual surfactants and Au (111) plane were calculated using molecular
      dynamics simulations. Based on a series of contrast experiments and molecular
      dynamics simulations, the possible growth mechanism and fabrication process of
      the dendritic structures were proposed. The DTAB-capped, three-fold gold
      dendrites exhibited good surface-enhanced Raman scattering (SERS) sensitivity
      toward rhodamine 6G (R6G), indicating their potential for use in SERS-based
      detections and analysis. This work provides a simple and effective strategy for
      fabricating dendritic gold nanostructures in aqueous solutions.

PMID- 22877505
TI  - Platelets--to transfuse or not to transfuse.

PMID- 22877506
TI  - Therapeutic platelet transfusion versus routine prophylactic transfusion in
      patients with haematological malignancies: an open-label, multicentre, randomised
      study.
AB  - BACKGROUND: Routine prophylactic platelet transfusion is the standard of care for
      patients with severe thrombocytopenia. We assessed the effect of a new strategy
      of therapeutic platelet transfusion on the number of transfusions and safety in
      patients with hypoproliferative thrombocytopenia. METHODS: We did a multicentre,
      open-label, randomised parallel-group trial at eight haematology centres in
      Germany. Patients aged 16-80 years, who were undergoing intensive chemotherapy
      for acute myeloid leukaemia or autologous haemopoietic stem-cell transplantation
      for haematological cancers, were randomly assigned via a computer-generated
      randomisation sequence to receive either platelet transfusion when bleeding
      occurred (therapeutic strategy) or when morning platelet counts were 10*10(9) per
      L or lower (prophylactic strategy). Investigators undertaking interventions were
      not masked to group assignment. The primary endpoint was the number of platelet
      transfusions. Analysis was by intention to treat. This trial is registered,
      NCT00521664. FINDINGS: 197 patients were assigned the prophylactic strategy and
      199 the therapeutic strategy. Of 391 patients analysed, the therapeutic strategy
      reduced the mean number of platelet transfusions by 33.5% (95% CI 22.2-43.1;
      p<0.0001) in all patients (2.44 [2.22-2.67] in prophylactic group vs 1.63 [1.42
      1.83] in therapeutic group), 31.6% (18.6-42.6; p<0.0001) in those with acute
      myeloid leukaemia (2.68 [2.35-3.01] vs 1.83 [1.58-2.10]), and 34.2% (6.6-53.7;
      p=0.0193) in those who had had autologous transplantation (1.80 [1.45-2.15] vs
      1.18 [0.82-1.55]. We noted no increased risk of major haemorrhage in patients who
      had undergone autologous transplantation. In those with acute myeloid leukaemia,
      risk of non-fatal grade 4 (mostly CNS) bleeding was increased. We recorded 15
      cases of non-fatal haemorrhage: four retinal in each transfusion group, and one
      vaginal and six cerebral in the therapeutic group. 12 patients died in the study:
      two from fatal cerebral haemorrhages in the therapeutic group, and ten (five in
      each treatment group) unrelated to major bleeding. INTERPRETATION: The
      therapeutic strategy could become a new standard of care after autologous stem
      cell transplantation; however, prophylactic platelet transfusion should remain
      the standard for patients with acute myeloid leukaemia. The new strategy should
      be used by some haematology centres only if the staff are well educated and
      experienced in the new approach and can react in a timely way to first signs of
      CNS bleeding. FUNDING: Deutsche Krebshilfe eV (German Cancer Aid).

PMID- 22877507
TI  - Sleep disturbances in 'migraine without aura'--a questionnaire based study.
AB  - OBJECTIVE: To evaluate the sleep abnormalities in patients with 'migraine without
      aura' in comparison to an age and gender matched control population. METHODOLOGY:
      Ninety patients with 'migraine without aura' who were not on migraine prophylaxis
      were prospectively recruited. Ninety age/gender matched healthy controls were
      recruited from a cohort of 1150 individuals who were for detection of the
      prevalence of sleep abnormalities in the general population. The frequency and
      duration of migraine attacks/disability was assessed using the migraine
      disability assessment score (MIDAS) scale. Sleep quality and excessive daytime
      sleepiness were assessed using the Pittsburgh sleep quality index (PSQI) and
      Epworth sleepiness scale (ESS). NIMHANS comprehensive sleep disorders
      questionnaire (NCSDQ) was used to screen for various sleep abnormalities.
      RESULTS: Among the 90 patients, 60 patients (66.7%) had a poor sleep quality as
      determined by a PSQI score of >=6 as against 7 controls (7.8%) and this was
      statistically significant (p=0.001). Thirteen patients (14.4%) had excessive
      daytime sleepiness (EDS) as measured by ESS score of >= 11 as compared to 1.1% in
      the controls (p=0.001). Patients with 'migraine without aura' have a much higher
      prevalence of non-refreshing sleep, nocturnal sweating and morning dryness of
      mouth as compared to healthy controls (p=0.001). They also had a higher
      prevalence of sleep paralysis, restless legs syndrome, nocturnal myoclonic jerks
      and sedative usage as compared to the controls (p=0.001). CONCLUSIONS: Patients
      with 'migraine without aura' have a much higher prevalence of sleep abnormalities
      as compared to controls which may be due to multiple contributory factors.

PMID- 22877508
TI  - White matter abnormalities correlate with neurocognitive performance in patients
      with HBV-related cirrhosis.
AB  - BACKGROUND: White matter (WM) abnormalities are common in cirrhotic patients and
      possibly contribute to hepatic encephalopathy (HE), a frequent neuropsychiatric
      complication of cirrhosis. However, little is known about these WM abnormalities
      and their relationship to neurocognitive deficits in patients with HBV-related
      cirrhosis. METHODS: Three-dimensional T1-weighted magnetic resonance imaging and
      diffusion tensor imaging (DTI) scans were obtained from 67 patients with HBV
      related cirrhosis and 40 controls. Voxel-based morphometry and voxel-based DTI
      were performed to detect macroscopic atrophy and damage to the microstructural
      integrity of the WM, respectively. Correlation analyses were performed to
      investigate the relationships between WM abnormalities and neurocognitive
      performances. RESULTS: Patients with cirrhosis exhibited significantly decreased
      WM volume and fractional anisotropy (FA) values, especially in the corpus
      callosum, thalamus, extra-nuclear area, sensorimotor area, fusiform gyrus,
      lingual gyrus, and frontal lobes. These abnormalities were more severe with
      increasing Child-Pugh stage, minimal HE, and previous overt HE. Changes in the
      corpus callosum, frontal lobe, sensorimotor area, internal capsule, and temporal
      occipital lobes were correlated with poor neurocognitive performance. Also, the
      significantly decreased global WM volume and mean FA value were correlated with
      poor neurocognitive performances. CONCLUSIONS: Diffuse WM abnormalities are
      common in patients with HBV-related cirrhosis. Advanced liver disease and
      episodes of HE are two factors associated with WM abnormalities. The correlation
      between poor neurocognitive performance and WM abnormalities suggests that WM
      abnormalities may be one of mechanisms underlying neurocognitive deficits in
      patients with HBV-related cirrhosis.

PMID- 22877509
TI  - Cognitive deficit is related to immune-cell beta-NGF in multiple sclerosis
      patients.
AB  - OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and
      neurodegenerative disease of the central nervous system (CNS), causing cognitive
      impairment in 45-65% of patients. Beta-NGF facilitates proper cholinergic
      transmission in the healthy CNS. In MS-damaged tissue there is a relative deficit
      of neurotrophins that might be compensated by peripheral blood mononuclear cells
      (PBMCs) synthesis. Our aim was to evaluate the relationship between PBMCs
      neurotrophins' expression and cognitive performance in relapsing-remitting MS
      (RRMS) patients. PATIENTS AND METHODS: Beta-NGF, NT-3 and NT-4/5 levels were
      measured in sera and in PBMCs by ELISA method in 41 RRMS patients in remission.
      All patients underwent neuropsychological assessment with a battery of 10 tests
      evaluating a wide range of cognitive functions. RESULTS: PBMCs beta-NGF
      concentration correlated significantly with spontaneous word list generation test
      (Pearson R=0.37, p=0.02) and 15-Word List Recall Test results (Pearson R=0.40,
      p<0.00). Both tests assessing semantic memory correlated significantly with the
      cognitive composite score, defined as a number of tests in which patients
      performed below group median for the given test. CONCLUSIONS: In RRMS beta-NGF is
      strongly linked to cognitive performance, which makes it an attractive
      therapeutic target. It might play a neuroprotective role in MS, especially in the
      cognitive domain.

PMID- 22877510
TI  - Epidemiology of dementia in Asia: insights on prevalence, trends and novel risk
      factors.
AB  - Asia is the most populous region in the world and its rapidly growing societies
      are the sources of global development. However, accompanying this rapid growth is
      aging of the population with increasing occurrence of diseases, of which dementia
      is the most prominent, which provide major challenges to healthcare systems.
      Dementia prevalence in Asia has previously been found to be lower than Western
      populations, but recent studies show that age-specific prevalence rates are
      similar globally. Overall dementia prevalence is expected to rise dramatically
      across Asia due to maturing populations. Earlier Asian studies reported a lower
      prevalence of Alzheimer's disease (AD) and a higher prevalence of vascular
      dementia (VaD). Recent studies, however, show a reversal of this ratio that now
      parallels that of Western countries. This change may be attributed to an altered
      demographic profile, urbanization, environmental reactions, ethnicity and
      advances in the use of neuroimaging modalities. Several factors may influence the
      results of epidemiological studies including changes in societal perception of
      aging, family attitudes, validity of assessment tools due to language and
      literacy, and medical practitioners' expertise in recognizing dementia.
      Nevertheless, epidemiological studies in Asia may reveal factors contributory to
      inter-ethnic differences in dementia. Potentially modifiable risk factors
      apparent only in low and middle-income countries and gene-environment
      interactions may underlie these disparities and identification of such factors
      may lead to effective treatments.

PMID- 22877511
TI  - The galactosaminoglycan-containing decorin and its impact on diseases.
AB  - Decorin, a member of the small leucine-rich proteoglycans, is involved in many
      physiological and pathological processes. Decorin functions not only as
      structural molecule in organizing the extracellular matrix but also as signaling
      molecule controlling cell growth, morphogenesis and immunity. Mutations in
      decorin or alterations in the post-translational modifications of the
      glycosaminoglycan (GAG) chain lead to connective tissue disorders such as the
      congenital stromal corneal dystrophy and the Ehlers-Danlos syndrome. The
      summarized data reveal that decorin has a large impact on biological processes
      also because of the complex structure of the GAG chain. The complexity of decorin
      also covers the binding and sequestering of growth factors and their signaling.
      This shows that the decorin protein and the dermatan sulfate chain of decorin
      have both a structural function and a signaling function. Since defects in the
      biosynthesis of either the protein core or the GAG chain lead to structural
      alterations in the extracellular matrix and changes in the protein expression
      profile of the cells embedded in the matrix, this review focuses on the insights
      of structural function of decorin and includes data about dermatan sulfate.

PMID- 22877512
TI  - A population-based study of familial and individual-specific environmental
      contributions to traumatic event exposure and posttraumatic stress disorder
      symptoms in a Norwegian twin sample.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is one of the only disorders in
      the Diagnostic and Statistical Manual of Mental Disorders that requires an
      environmental exposure. The relationship between liability factors for trauma
      exposure and those for PTSD symptoms following exposure are unclear. METHODS:
      Exposure to a trauma and resulting PTSD symptoms were assessed in a sample of
      2,794 members of the Norwegian Institute of Public Health Twin Panel. RESULTS: In
      the full sample, 737 twins experienced a trauma. A modified causal, contingent,
      common pathway model was used to examine trauma exposure and liability for PTSD.
      Genetic and common environmental factors could not be distinguished, so a model
      that included only familial and individual specific components was fit. The best
      fitting model suggested that familial factors played an important role in
      liability for trauma exposure and for resulting PTSD symptoms, and that there was
      a modest transmission between trauma exposure and subsequent PTSD symptoms.
      CONCLUSIONS: One third of the variance in liability of PTSD symptoms is due to
      familial factors, and of this, approximately one fifth overlaps with the familial
      liability for trauma exposure while the other four fifths of the variance is
      specific to the risk of PTSD symptoms following exposure. The hypothesis that
      PTSD is etiologically similar to exposures to a traumatic event is not supported,
      suggesting that the factors that confer risk for trauma do not overlap completely
      with those that confer risk for PTSD.

PMID- 22877513
TI  - Update of cases of acute hepatitis E confirmed by the National Centre of
      Microbiology (Spain, 2004-2011).

PMID- 22877514
TI  - The timing and temporal patterns of eye blinking are dynamically modulated by
      attention.
AB  - A number of human behaviors and movements show self-similar temporal patterns in
      their occurrence over time. Human walking, finger tapping and heartbeat intervals
      have fluctuations that are statistically similar at multiple time scales.
      However, whether eye blinking, which is a unique human behavior that occurs
      spontaneously, embeds a similar temporal structure within other types of
      movements is largely unknown. In this study, we used attention-requiring tasks to
      assess how the temporal pattern of eye blinking is altered in both the second and
      sub-second time scales. Our results showed that eyeblink activity was more
      suppressed as the task difficulty level increased and was facilitated immediately
      after exposure to auditory stimuli, which were presented for 6 to 14s. Moreover,
      similar transient suppressive and facilitative patterns were observed in the
      response period, which lasted for less than one second. Furthermore, we found
      that spontaneous eye blinking intervals fluctuated according to an 1/f scaling
      property, which is widely observed in various human movements. These results
      suggest that the dynamics of eye blinking under specific cognitive tasks exhibit
      a similar temporal structure at multiple time scales.

PMID- 22877516
TI  - Quantitative determination of organic semiconductor microstructure from the
      molecular to device scale.

PMID- 22877515
TI  - Dietary intake in pregnant women in a Spanish Mediterranean area: as good as it
      is supposed to be?
AB  - OBJECTIVE: To assess food and nutrient intakes and compliance with nutritional
      recommendations in pregnant women according to selected sociodemographic
      characteristics. DESIGN: Cross-sectional study based on data from the INMA
      Valencia cohort (Spain), which recruited pregnant women between 2004 and 2005.
      Information on maternal sociodemographics and anthropometry was collected.
      Dietary intake was assessed through an FFQ. Intakes of foods were compared with
      Spanish food-based dietary guidelines. Intake inadequacy for nutrients was
      assessed using the Dietary Reference Intakes of the US Institute of Medicine.
      SETTING: Valencia, Spain. SUBJECTS: We studied 822 pregnant women who had
      information on dietary intake during their first trimester of pregnancy. RESULTS:
      More than 50% of pregnant women did not meet the guidelines for cereals and
      legumes; reported intakes of carbohydrates, n-3 and n-6 fatty acids were below
      recommendations and exceeded the total fat intake according to dietary
      references. Dietary inadequacy for folate, Fe and vitamin E ranged from 99% to
      68%. Vegetable intake was related to age only. Younger and less educated women
      showed lower intakes of protein and n-3 fatty acids and higher intakes of trans
      fatty acids as well as greater inadequacy for micronutrients. Spanish women
      reported lower intakes of fruit and carbohydrates and higher intakes of protein,
      total fat, SFA, MUFA and n-3 fatty acids compared with their foreign-born
      counterparts. CONCLUSIONS: Women in the studied area have inadequate intakes of
      several nutrients relevant during pregnancy. Age, education and country of origin
      are factors significantly related to dietary intake and adequacy.

PMID- 22877517
TI  - Mechanisms accounting for fluoroquinolone multidrug resistance Escherichia coli
      isolated from companion animals.
AB  - Multidrug resistance (MDR) is associated with fluoroquinolone (FQ) resistance in
      companion animal Escherichia coli (E. coli). In this study, gyrA, gyrB, parC, and
      parE quinolone resistance determining regions (QRDR) were sequenced among
      uropathogenic E. coli isolates with different resistant phenotypes. Also
      determined were porin, efflux pump and regulatory gene expression based on
      quantitative real-time reverse transcriptase PCR (qRT-PCR), the impact of efflux
      pump inhibition (Phe-Arg-beta-naphthylamide) and the presence of plasmid-mediated
      quinolone resistance (PMQR). Using enrofloxacin as the prototypic FQ, we found
      that (i) the number of mutations in target genes correlate well with minimum
      inhibitory concentrations (MICs). A single mutation (Ser83Leu) in gyrA increases
      FQ MIC in susceptible isolates; subsequent mutations result in resistance that
      increases from low (enrofloxacin MICs 4-16 MUg/ml) to high level (enrofloxacin
      MICs>=128 MUg/ml) with each progressive mutation. (ii) as MIC increase, acrB
      activity and the number of drug classes contributing to the MDR phenotype
      increases; (iii) a consistent relationship between regulatory gene expression and
      MIC could not be identified; and (iv) qnrS and aac(6')-Ib-cr gene were detected
      in 14 and 5 ENR(R)-MDR isolates containing the target mutation, respectively. Of
      13 isolates expressing PDR isolates, 10 (77%) were positive for qnrS gene, and 4
      (40%) carried both qnrS and aac(6')-Ib-cr gene. These findings demonstrated that
      MDR-associated FQ resistance in canine and feline uropathogenic E. coli reflects
      a combination of point mutations, enhanced efflux pump activities, and PMQR
      mechanisms. Point mutations in DNA gyrase, however, are necessary to achieve a
      clinical level of FQ resistance.

PMID- 22877518
TI  - Distribution and molecular characterization of Porphyromonas gulae carrying a new
      fimA genotype.
AB  - Porphyromonas gulae is a gram-negative black-pigmented anaerobe which is known to
      be a pathogen for periodontitis in dogs. Approximately 41kDa filamentous
      appendages on the cell surface (FimA) encoded by the fimA gene are regarded as
      important factors associated with periodontitis. The fimA genotype was classified
      into two major types and strains in type B were shown to be more virulent than
      those in type A. In the present study, we characterized a strain with a novel
      fimA genotype and designated it as type C. The putative amino acid sequence was
      shown to be similar to the genotype IV fimA of Porphyromonas gingivalis, a major
      pathogen of human periodontitis. Analyses using an oral squamous cell carcinoma
      cell line derived from tongue primary lesions revealed that the type C strain
      inhibited proliferation and scratch closure more than genotype A and B strains.
      In addition, experiments using a mouse abscess model demonstrated that the type C
      strain could induce much higher systemic inflammation when compared with strains
      of the other genotypes. Furthermore, molecular analyses of oral swab specimens
      collected from dogs demonstrated that the detection frequencies of P. gulae and
      the genotype C in the periodontitis group were significantly higher than those in
      the periodontally healthy group. These results suggest that FimA of P. gulae is
      diverse with the virulence of genotype C strains the highest and that molecular
      identification of genotype C P. gulae could be a possible useful marker for
      identifying dogs at high risk of developing periodontitis.

PMID- 22877559
TI  - Structural transitions of CTAB micelles in a protic ionic liquid.
AB  - Micellar solutions of hexadecyltrimethylammonium bromide (CTAB) in a protic ionic
      liquid, ethylammonium nitrate (EAN), are studied by shear rheology, polarizing
      optical microscopy (POM), conductivity measurements, and small angle neutron
      scattering (SANS). Three concentration regimes are examined: A dilute regime
      (with concentrations [CTAB] < 5 wt %) consisting of noninteracting spherical
      micelles, a semidilute regime (5 wt % <= [CTAB] <= 45 wt %) where micelles
      interact via electrostatic repulsions, and a concentrated regime (45 wt % <
      [CTAB] <= 62 wt %) where a reversible, temperature-dependent isotropic (L(1)) to
      hexatic (Hex) phase transition is observed. The L(1)-Hex transition, which has
      been predicted but not previously observed, is characterized by (1) a sharp
      increase in the shear viscosity, (2) the formation of focal conical birefringence
      textures (observed by POM), and (3) enhancement of the crystalline order,
      evidenced by the appearance of Bragg reflections in the SANS profiles. Ionic
      conductivity is not sensitive to the L(1)-Hex transition, which corroborates the
      absence of topological transitions.

PMID- 22877519
TI  - Discovery and molecular characterization of a group A rotavirus strain detected
      in an Argentinean vicuna (Vicugna vicugna).
AB  - The wild vicuna (Vicugna vicugna) is one of the four species of native South
      American camelids (SACs) in addition to the wild guanaco, and their domesticated
      counterparts, alpaca and llama, respectively. Serological data have indicated the
      presence of group A rotaviruses (RVA) specific antibodies in all 4 members of the
      SAC, and so far, RVA has been detected from alpacas, llamas and guanacos. A total
      of 59 fecal samples from healthy wild newborn and juvenile vicunas, raised in
      captivity in Jujuy, Argentina were collected and analyzed by ELISA to detect RVA
      antigen. Two samples (3%) were found to contain G8 RVA strains and one strain
      (RVA/Vicuna-wt/ARG/C75/2010/G8P[14]) was selected for further genome analyses,
      revealing the G8-P[14]-I2-R2-C2-M2-Ax-N2-T6-E3-Hx genotype constellation.
      Unfortunately, no sequence data could be obtained for NSP1 and NSP5. Except for
      the E3 NSP4 genotype, this partial genotype constellation is reminiscent to
      bovine RVA strains and bovine-like RVA strains isolated from sheep, guanaco,
      antelope and humans. This relationship was confirmed phylogenetically, providing
      further evidence of the widespread presence of this genotype constellation in
      animals belonging to the artiodactyls. In particular, a close phylogenetic
      relationship was found between C75 and guanaco RVA strain RVA/Guanaco
      wt/ARG/Chubut/1999/G8P[14] for at least 5 gene segments, suggesting a partial
      conservation of the genotype constellation of RVA strains infecting different
      species of SACs, even though nowadays their natural habitats are not overlapping.
      The further monitoring of the sanitary health of wild newborn and juvenile
      vicunas is essential to improve the management practices applied in their
      sustainable exploitation.

PMID- 22877560
TI  - Hantavirus infections by Puumala or Dobrava-Belgrade virus in pregnant women.
AB  - BACKGROUND: Hantavirus infection in humans usually occurs via inhalation of
      infectious aerosolized excreta of rodents. Horizontal human-to-human transmission
      was reported only for the highly virulent Andes virus. The likelihood of vertical
      transmission and the clinical outcome of hantavirus infections in pregnancy is
      still unpredictable. OBJECTIVES: Very few data were published about the impact of
      hantaviruses in pregnancy. Here we present four cases of pregnant women infected
      by European hantaviruses. The risk of vertical virus transmission was
      investigated. STUDY DESIGN: Four pregnant women with clinical signs of acute
      hantavirus disease were investigated for hantavirus IgM and IgG after onset of
      clinical symptoms. Furthermore, the newborns were tested for presence of viral
      RNA and antibodies in cord blood and, if any parameter was found positive, 8-12
      months after delivery. RESULTS: Four women suffered from a hantavirus infection,
      two of them due to infection by Puumala virus and two by Dobrava-Belgrade virus.
      Three women delivered healthy babies by vaginal route and one woman by Caesarean
      section (week 28). In no case hantavirus RNA was detected in cord blood after
      delivery or in the 8-12 month old babies. Hantavirus IgG was detectable in the
      cord blood of 3 babies (but not in the preterm child); these antibodies
      disappeared after 8-12 months indicating a passive transfer of immunoglobulins.
      No child had any clinical sign of hantavirus infection. CONCLUSIONS: In this
      study, the absence of vertical hantavirus transmission was demonstrated for
      pregnant women with onset of hantavirus disease between gestation weeks 14 and
      28.

PMID- 22877561
TI  - Comparison of INNO-LiPA genotyping extra and hybrid capture 2 assays for
      detection of carcinogenic human papillomavirus genotypes.
AB  - BACKGROUND: Accurate HPV detection and genotyping tests are useful for management
      of women with HPV infection and for monitoring HPV vaccine efficacy. OBJECTIVES:
      To evaluate the performance of the INNO-LiPA HPV Genotyping Extra assay (SPF10
      LiPA) for the detection of carcinogenic HPV types in women referred for
      opportunistic cervical cancer screening by comparison with the Hybrid Capture 2
      (HC2) assay. STUDY DESIGN: Cross-sectional analysis from baseline data of HC2 and
      SPF10-LiPA testing in cervical specimens collected from 1580 consecutive women
      and correlation with cervical cytology and histology data, when available.
      RESULTS: The two assays showed a good agreement for detection of carcinogenic HPV
      types and reported the same prevalence of carcinogenic HPV infections in
      different age groups. Stratification of study subjects by cervical cytology
      interpretation and histology results demonstrated that the two tests gave very
      similar results in the different cytology interpretation groups and in CIN2 and
      CIN3 samples, while in <CIN2 samples the SPF10-LiPA assay provided a
      significantly lower number of carcinogenic HPV-positive results than the HC2
      test. A comparative analysis of the two assay for individual HPV types showed
      that HC2 identified as positive between 73% and 100% of specimens with
      carcinogenic HPV types detected by SPF10-LiPA and, in particular, approximately
      90% and 80% of HPV16- and HPV18-positive samples, respectively. CONCLUSIONS: A
      good agreement was observed between HC2 and SPF10-LiPA for carcinogenic HPV type
      detection, that supports further evaluation of the clinical performance of the
      new version of SPF10-LiPA in cervical cancer screening protocols.

PMID- 22877562
TI  - Molecular epidemiology and clinical manifestations of human cryptosporidiosis in
      Sweden.
AB  - This study describes the epidemiology and symptoms in 271 cryptosporidiosis
      patients in Stockholm County, Sweden. Species/genotypes were determined by
      polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) of
      the Cryptosporidium oocyst wall protein (COWP) and 18S rRNA genes. Species were
      C. parvum (n=111), C. hominis (n=65), C. meleagridis (n=11), C. felis (n=2),
      Cryptosporidium chipmunk genotype 1 (n=2), and a recently described species, C.
      viatorum (n=2). Analysis of the Gp60 gene revealed five C. hominis allele
      families (Ia, Ib, Id, Ie, If), and four C. parvum allele families (IIa, IIc, IId,
      IIe). Most C. parvum cases (51%) were infected in Sweden, as opposed to C.
      hominis cases (26%). Clinical manifestations differed slightly by species.
      Diarrhoea lasted longer in C. parvum cases compared to C. hominis and C.
      meleagridis cases. At follow-up 25-36 months after disease onset, 15% of the
      patients still reported intermittent diarrhoea. In four outbreaks and 13 family
      clusters, a single subtype was identified, indicating a common infection source,
      which emphasizes the value of genotyping for epidemiological investigations.

PMID- 22877563
TI  - What's really delaying the defeat of aging?

PMID- 22877564
TI  - Exhaled matrix metalloproteinase-9 in lung cancer.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has been recognized in several
      types of tumor development and progression, including lung cancer, for its role
      in the degradation and remodeling of lung tissue. Furthermore, increased MMP-9
      has been commonly described in the serum and airways of non-small cell lung
      cancer (NSCLC) patients. OBJECTIVE: The aim of this study was to investigate, for
      the first time, MMP-9 in the exhaled breath condensate (EBC) of NSCLC patients.
      PARTICIPANTS: We enrolled 40 NSCLC patients and 40 controls affected by
      transudative pleural effusion. MEASUREMENTS: MMP-9 concentrations were measured
      in the EBC, whole blood (WB), and pleural effusion (PE) of all the subjects under
      study using enzyme immunoassay (EIA) kits. RESULTS: MMP-9 levels were found to be
      significantly higher in EBC, WB, and PE of NSCLC patients compared with controls.
      A positive correlation was observed between MMP-9 in EBC, cigarettes smoked, and
      stage of cancer. CONCLUSION: Exhaled MMP-9 was elevated in NSCLC patients,
      especially during tumor progression, and could represent a suitable noninvasive
      marker in the diagnosis and monitoring of lung cancer.

PMID- 22877565
TI  - Vascular endothelial growth factor downregulates apolipoprotein M expression by
      inhibiting Foxa2 in a Nur77-dependent manner.
AB  - OBJECTIVE: We aimed to investigate whether vascular endothelial growth factor
      (VEGF) influences apolipoprotein M (ApoM) expression and pre-beta-high-density
      lipoprotin (HDL) formation, and whether forkhead box A2 (Foxa2) and Nur77 are
      involved in this process. METHODS AND RESULTS: We analyzed the serum VEGF
      concentrations of 264 adults who underwent a medical checkup and found that VEGF
      concentration was positively correlated with serum triglyceride, total
      cholesterol, LDL cholesterol (LDL-C), very-low-density lipoprotein cholesterol
      (VLDL-C), and ApoB concentrations, but was negatively correlated with serum high
      density lipoprotein cholesterol (HDL-C) and ApoM concentrations. We further
      investigated the effects of VEGF on ApoM expression and pre-beta-HDL formation,
      and the mechanisms responsible, in HepG2 cells and mouse primary hepatocytes.
      VEGF markedly downregulated ApoM expression and pre-beta-HDL formation. At the
      same time, expression of Foxa2 was also inhibited, whereas expression of Nur77
      was increased by treatment with VEGF. Furthermore, small interfering (si) RNA
      knockdown of Foxa2 made the downregulation of VEGF on ApoM expression and pre
      beta-HDL formation even more obvious. In addition, siRNA knockdown of Nur77
      significantly compensated for the inhibitory effect of VEGF on Foxa2 expression,
      whereas the Nur77 agonist cytosporone B led to the downregulation of Foxa2
      expression more significantly than VEGF. Moreover, overexpression of a Nur77
      transgene in C57BL/6 mice resulted in decreased serum ApoM and pre-beta-HDL
      levels, whereas si-Nur77-treated mice displayed upregulated serum ApoM and pre
      beta-HDL levels. CONCLUSION: These results provide evidence that VEGF may first
      downregulate expression of Foxa2 by enhancing Nur77 activity and then decrease
      expression of ApoM and pre-beta-HDL formation. Therefore, our study may be useful
      in understanding the critical effect of VEGF in the pathogenesis of
      atherosclerosis.

PMID- 22877566
TI  - Ectopic expression of telomerase safely increases health span and life span.
AB  - The absence of telomerase from somatic cells of mammals has significant
      consequences for aging. First, it limits the number of potential cell divisions
      and in so doing sets limits on both life span and cancer cell proliferation.
      Second, shortened telomeres are known to result in physiological dysfunction,
      including playing a role in human diseases such as Werner syndrome and ataxia
      telangiectasia. Ectopic expression of the catalytic subunit of telomerase,
      telomerase reverse transcriptase (TERT), has been reported to extend life span by
      as much as 40% in cancer-resistant mice. On the other hand, ectopic expression of
      TERT promotes cancer in normal mice. However, transient induction of TERT by an
      astragalus-derived compound increases health span without an apparent increase in
      cancer incidence. Ectopic expression of TERT using adeno-associated virus
      serotype 9 (AAV9)-based gene therapy in adult mice increases both health span and
      life span without increasing cancer incidence. Available evidence suggests that
      increases in life span may require both elongated telomeres and the continuous
      presence of telomerase to stimulate the WNT/beta-catenin signaling pathway. The
      recent observation that WNT/beta-catenin signaling can stimulate TERT expression
      raises the possibility of a positive feedback loop between TERT and WNT/beta
      catenin. Such a positive feedback loop implies that safety must be carefully
      considered in the development of drugs that stimulate telomerase activity.

PMID- 22877568
TI  - Molecularly imprinted polymer of bis(2,2'-bithienyl)methanes for selective
      determination of adrenaline.
AB  - New chemical sensors for adrenaline Adr were fabricated. For that, a thin film of
      a molecularly imprinted polymer (MIP) was templated with protonated adrenaline
      HAdr. Differential pulse voltammetry (DPV), capacitive impedometry (CI), or
      piezoelectric microgravimetry (PM) was integrated within each chemosensor for
      analytical signal transduction. First, molecular structure of prepolymerization
      complex of HAdr with bis(2,2'-bithienyl)methane substituted with the benzo-(18
      crown-6) 2 and 4-carboxyphenyl 3 was thermodynamically optimized at the B3LYP/6
      31g(d) level. Then, a HAdr-templated MIP film was deposited on the Pt disk
      electrode and on the Au film electrode of a 10-MHz quartz crystal resonator (QCR)
      by potentiodynamic electropolymerization from solution of HAdr, 2, 3, and the
      cross-linking tris([2,2'-bithiophen]-5-yl)methane 4 monomer at the HAdr:2:3:4 =
      1:1:1:2 mole ratio. For determination of Adr, the DPV peak current for the
      K4[Fe(CN)6] redox probe under batch conditions and the resonant frequency and
      capacity of the electrical double layer under FIA conditions were measured. The
      lower limits of detection (LOD) were 2 nM, 0.5 MUM, and 1.5 MUM for the DPV, PM,
      and CI chemosensor, respectively, indicating suitability of the DPV chemosensor
      for Adr determination in biological systems (-50 nM). The chemosensors were
      appreciably selective to Adr in the presence of common interferents.

PMID- 22877569
TI  - Design of a Candida albicans disaccharide conjugate vaccine by reverse
      engineering a protective monoclonal antibody.
AB  - A disaccharide-chicken serum albumin conjugate vaccine against Candida albicans
      infections has been developed by reverse engineering a protective monoclonal
      antibody, C3.1. The binding site of C3.1 binds short oligosaccharides of beta1,2
      linked mannopyranose residues present in the fungal cell wall phosphomannan. By
      delineating the fine detail of the molecular recognition of the cell wall beta
      mannan antigen, a disaccharide epitope was deduced to be the minimum size epitope
      that should induce the formation of protective antibody. Sequential functional
      group replacement of disaccharide hydroxyl groups to yield a series of monodeoxy
      and mono-O-methyl beta1,2-linked mannobioside congeners established that three
      hydroxyl groups are essential for binding. Two of these, O-3 and O-4, are located
      on the internal mannose residue of the disaccharide, and a third, O-3', is
      located on the terminal mannose. Synthesis of a series of trisaccharides that
      mandate binding of either the reducing or nonreducing disaccharide epitopes
      provided the final indication that a disaccharide protein conjugate should have
      the potential to induce protective antibody. When disaccharide was conjugated to
      chicken serum albumin this vaccine produced antibodies in rabbits that recognized
      the native cell wall phosphomannan. In proof of concept protection experiments,
      three immunized rabbits showed a reduction in fungal burden when challenged with
      live C. albicans.

PMID- 22877570
TI  - Autoamputation of breast caused by invasive ductal carcinoma.

PMID- 22877571
TI  - Providing additional money to food-insecure households and its effect on food
      expenditure: a randomized controlled trial.
AB  - OBJECTIVES: Financial constraint is the underpinning determinant of household
      food insecurity; however, there has been little research examining the impact
      that increasing the 'money available' to food-insecure households could have on
      food purchasing. The main objective of the present study was to examine the
      effect of additional money (in the form of supermarket vouchers) on food
      expenditure in food-insecure households with children. DESIGN: A parallel
      randomized controlled trial with a 4-week baseline phase followed by a 4-week
      intervention phase. Households were randomized to either receive vouchers
      (coupons) for 4 weeks or a control group that did not receive any vouchers.
      SETTING: Dunedin, New Zealand. SUBJECTS: Low-income households with children >=
      18 years) reporting food insecurity (n 214). RESULTS: The mean monetary value of
      the vouchers received by households was $NZ 17?00 per week. The voucher group
      spent >= NZ 15.20 (95% CI 1.46, 28.94) more per week on food during the
      intervention phase compared with the control group (P50.030). There were no
      differences in expenditure between the voucher and the control group for the food
      groups 'fruit and vegetables' (mean difference: >= NZ 0?46; 95% CI 21.97, 2.89;
      P50.709), 'meat and poultry' (mean difference: >= NZ 0.29; 95% CI 23.07, 3.64;
      P50.866) and 'dairy' (mean difference: >= NZ 0.82; 95% CI 20.75, 2.42; P50.302).
      CONCLUSIONS: Providing money via supermarket vouchers to food-insecure resulted
      in an increase in overall expenditure on food.

PMID- 22877572
TI  - Are community-level financial data adequate to assess population health
      investments?
AB  - The variation in health outcomes among communities results largely from different
      levels of financial and nonfinancial policy investments over time; these natural
      experiments should offer investment and policy guidance for a business model on
      population health. However, little such guidance exists. We examined the
      availability of data in a sample of Wisconsin counties for expenditures in
      selected categories of health care, public health, human services, income
      support, job development, and education. We found, as predicted by the National
      Committee on Vital and Health Statistics in 2002, that availability is often
      limited by the challenges of difficulty in locating useable data, a lack of
      resources among public agencies to upgrade information technology systems for
      making data more usable and accessible to the public, and a lack of enterprise
      wide coordination and geographic detail in data collection efforts. These
      challenges must be overcome to provide policy-relevant information for optimal
      population health resource allocation.

PMID- 22877573
TI  - Continuation with statin therapy and the risk of primary cancer: a population
      based study.
AB  - INTRODUCTION: Studies have suggested that statins may inhibit tumor cell growth
      and possibly prevent carcinogenesis. The objective of this study was to
      investigate the association between persistent statin use and the risk of primary
      cancer in adults. METHODS: This retrospective study was conducted by using the
      computerized data sets of a large health maintenance organization (HMO) in
      Israel. The study population was 202,648 enrollees aged 21 or older who purchased
      at least 1 pack of statin medication from 1998 to 2006. The follow-up period was
      from the date of first statin dispensation (index date) to the date of first
      cancer diagnosis, death, leaving the HMO, or September 1, 2007, whichever
      occurred first. Persistence was measured by calculating the mean proportion of
      follow-up days covered (PDC) with statins by dividing the quantity of statin
      dispensed by the total follow-up time. RESULTS: During the study period, 8,662
      incident cancers were reported. In a multivariable model, the highest cancer risk
      was calculated among nonpersistent statin users. A strong negative association
      between persistence with statin therapy and cancer risk was calculated for
      hematopoietic malignancies, where patients covered with statins in 86% or more of
      the follow-up time had a 31% (95% confidence interval, 0.55-0.88) lower risk than
      patients in the lowest persistence level (<= 12%). CONCLUSION: Our study
      demonstrated that persistent use of statins is associated with a lower overall
      cancer risk and particularly the risk of incident hematopoietic malignancies. In
      light of widespread statin consumption and increases in cancer incidence, the
      association between statins and cancer incidence may be relevant for cancer
      prevention.

PMID- 22877574
TI  - Modelling the within-host growth of viral infections in insects.
AB  - Insects are infected by a variety of pathogens, including bacteria, fungi and
      viruses, which have been studied largely for their potential as biocontrol
      agents, but are also important in insect conservation (biodiversity) and as model
      systems for other diseases. Whilst the dynamics of host-pathogen interactions are
      well-studied at the population level, less attention has been paid to the
      critical within-host infection stage. Here, the reproductive rate of the pathogen
      is largely determined by how it exploits the host; the resources supplied by the
      host in terms of size and condition; competition with other pathogens; and the
      speed with which it kills the host (death being an inevitable outcome for
      obligate-killing pathogens). In this paper we aim to build upon recent
      developments in the literature by conducting single infection bioassays to obtain
      data on growth and fitness parameters for phenotypically different and similar
      strains of nucleopolyhedroviruses in the Lepdipoteran host Spodoptera exigua.
      Using these data, a simple mechanistic mathematical model (a coupled system of
      differential equations) is derived, fitted and parameter sensitivity predictions
      are made which support empirical findings. We unexpectedly found that initial
      growth of virus within the host occurs at a double-exponential rate, which
      contrasts with empirical findings for vertebrate host-pathogen systems. Moreover,
      these infection rates differ between strains, which has significant implications
      for the evolution of virulence and strain coexistence in the field, which are
      still relative unknowns. Furthermore, our model predicts that, counter to
      intuition, increased viral doses may lead to a decrease in viral yield, which is
      supported by other studies. We explain the mechanism for this phenomenon and
      discuss its implications for insect host-pathogen ecology. 

PMID- 22877575
TI  - Conformational co-dependence between Plasmodium berghei LCCL proteins promotes
      complex formation and stability.
AB  - Malaria parasites express a conserved family of LCCL-lectin adhesive-like domain
      proteins (LAPs) that have essential functions in sporozoite transmission. In
      Plasmodium falciparum all six family members are expressed in gametocytes and
      form a multi-protein complex. Intriguingly, knockout of P. falciparum LCCL
      proteins adversely affects expression of other family members at protein, but not
      at mRNA level, a phenomenon termed co-dependent expression. Here, we investigate
      this in Plasmodium berghei by crossing a PbLAP1 null mutant parasite with a
      parasite line expressing GFP-tagged PbLAP3 that displays strong fluorescence in
      gametocytes. Selected and validated double mutants show normal synthesis and
      subcellular localization of PbLAP3::GFP. However, GFP-based fluorescence is
      dramatically reduced without PbLAP1 present, indicating that PbLAP1 and PbLAP3
      interact. Moreover, absence of PbLAP1 markedly reduces the half-life of PbLAP3,
      consistent with a scenario of misfolding. These findings unveil a potential
      mechanism of conformational interdependence that facilitates assembly and
      stability of the functional LCCL protein complex.

PMID- 22877576
TI  - An individual-based model applied to the study of different fishing strategies of
      Pintado Pseudoplatystoma corruscans (Agassiz, 1829).
AB  - The decline in stocks of commercial fish species has been documented in several
      regions of the world. This decline is due partially to the effect of evolutionary
      pressure caused by the management of fishing activity, which reduces the size of
      fish after a few generations. In this paper, the population dynamics of the
      Pintado Pseudoplatystoma corruscans, one of the main commercial species of
      freshwater fish in Brazil, were simulated considering different scenarios of
      fishing mortality and different minimum and maximum lengths of capture. The
      results show that selective fishing based on the different proposed selectivity
      curves can result in an evolution-mediated increase in the growth rate of the
      fish, the biomass and the catch. This suggests that appropriate changes in
      Brazilian legislation can contribute to the sustainability of fisheries and to
      conservation of the fish stocks exploited by man.

PMID- 22877577
TI  - Let's face it, from trial to trial: comparing procedures for N170 single-trial
      estimation.
AB  - The estimation of event-related single trial EEG activity is notoriously
      difficult but is of growing interest in various areas of cognitive neuroscience,
      such as multimodal neuroimaging and EEG-based brain computer interfaces. However,
      an objective evaluation of different approaches is lacking. The present study
      therefore compared four frequently-used single-trial data filtering procedures:
      raw sensor amplitudes, regression-based estimation, bandpass filtering, and
      independent component analysis (ICA). High-density EEG data were recorded from 20
      healthy participants in a face recognition task and were analyzed with a focus on
      the face-selective N170 single-trial event-related potential. Linear discriminant
      analysis revealed significantly better single-trial estimation for ICA compared
      to raw sensor amplitudes, whereas the other two approaches did not improve
      classification accuracy. Further analyses suggested that ICA enabled extraction
      of a face-sensitive independent component in each participant, which led to the
      superior performance in single trial estimation. Additionally, we show that the
      face-sensitive component does not directly represent activity from a neuronal
      population exclusively involved in face-processing, but rather the activity of a
      network involved in general visual processing. We conclude that ICA effectively
      facilitates the separation of physiological trial-by-trial fluctuations from
      measurement noise, in particular when the process of interest is reliably
      reflected in components representing the neural signature of interest.

PMID- 22877578
TI  - Changes in functional connectivity support conscious object recognition.
AB  - What are the brain mechanisms that mediate conscious object recognition? To
      investigate this question, it is essential to distinguish between brain processes
      that cause conscious recognition of a stimulus from other correlates of its
      sensory processing. Previous fMRI studies have identified large-scale brain
      activity ranging from striate to high-level sensory and prefrontal regions
      associated with conscious visual perception or recognition. However, the possible
      role of changes in connectivity during conscious perception between these regions
      has only rarely been studied. Here, we used fMRI and connectivity analyses,
      together with 120 custom-generated, two-tone, Mooney images to directly assess
      whether conscious recognition of an object is accompanied by a dynamical change
      in the functional coupling between extrastriate cortex and prefrontal areas. We
      compared recognizing an object versus not recognizing it in 19 naive subjects
      using two different response modalities. We find that connectivity between the
      extrastriate cortex and the dorsolateral prefrontal cortex (DLPFC) increases when
      objects are consciously recognized. This interaction was independent of the
      response modality used to report conscious recognition. Furthermore, computing
      the difference in Granger causality between recognized and not recognized
      conditions reveals stronger feedforward connectivity than feedback connectivity
      when subjects recognized the objects. We suggest that frontal and visual brain
      regions are part of a functional network that supports conscious object
      recognition by changes in functional connectivity.

PMID- 22877579
TI  - Larger is twistier: spectral analysis of gyrification (SPANGY) applied to adult
      brain size polymorphism.
AB  - The description of cortical folding pattern (CFP) is challenging because of
      geometric complexity and inter-subject variability. On a cortical surface mesh,
      curvature estimation provides a good scalar proxy of CFP. The oscillations of
      this function can be studied using a Fourier-like analysis to produce a power
      spectrum representative of the spatial frequency composition of CFP. First, we
      introduce an original method for the SPectral ANalysis of GYrication (Spangy),
      which performs a spectral decomposition of the mean curvature of the grey/white
      interface mesh based on the Laplace-Beltrami operator eigenfunctions. Spangy
      produces an ordered 7 bands power spectrum of curvature (B0-B6) and provides an
      anatomically relevant segmentation of CFP based on local spectral composition. A
      spatial frequency being associated with each eigenfunction, the bandwidth design
      assumes frequency doubling between consecutive spectral bands. Next, we observed
      that the last 3 spectral bands (B4, 5 and 6) accounted for 93% of the analyzed
      spectral power and were associated with fold-related variations of curvature,
      whereas the lower frequency bands were related to global brain shape. The
      spectral segmentation of CFP revealed 1st, 2nd and 3rd order elements associated
      with B4, B5 and B6 respectively. These elements could be related to
      developmentally-defined primary, secondary and tertiary folds. Finally, we used
      allometric scaling of frequency bands power and segmentation to analyze the
      relationship between the spectral composition of CFP and brain size in a large
      adult dataset. Total folding power followed a positive allometric scaling which
      did not divide up proportionally between the bands: B4 contribution was constant,
      B5 increased like total folding power and B6 much faster. Besides, apparition of
      new elements of pattern with increasing size only concerned the 3rd order. Hence,
      we demonstrate that large brains are twistier than smaller ones because of an
      increased number of high spatial frequency folds, ramifications and kinks that
      accommodate the allometric increase of cortical surface.

PMID- 22877580
TI  - Spatiotemporal profiles of visual processing with and without primary visual
      cortex.
AB  - The spatiotemporal profiles of visual processing are normally distributed in two
      temporal phases, each lasting about 100 ms. Within each phase, cortical
      processing begins in V1 and traverses the visual cortical hierarchy. However, the
      causal role of V1 in starting each of these two phases is unknown. Here we used
      magnetoencephalography to study the spatiotemporal profiles of visual processing
      and the causal contribution of V1 in three neurologically intact participants and
      in a rare patient (GY) with unilateral destruction of V1, in whom residual visual
      functions mediated by the extra-geniculostriate pathways have been reported. In
      healthy subjects, visual processing in the first 200 ms post-stimulus onset
      proceeded in the two usual phases. Normally perceived stimuli in the left
      hemifield of GY elicited a spatiotemporal profile in the intact right hemisphere
      that closely matched that of healthy subjects. However, stimuli presented in the
      cortically blind hemifield produced no detectable response during the first phase
      of processing, indicating that the responses in extrastriate visual areas during
      this phase are determined by the feedforward progression of activity initiated in
      V1. The first responses occurred during the second processing phase, in the
      ipsilesional high-level visual areas. The activity then spread forward toward
      higher-level areas and backward toward lower-level areas. However, in contrast to
      responses in the intact hemisphere, the back-propagated activity in the early
      visual cortex did not exhibit the classic retinotopic organization and did not
      have well-defined response peaks.

PMID- 22877581
TI  - The epidemiology of meningococcal disease in Latin America 1945-2010: an
      unpredictable and changing landscape.
AB  - Meningococcal disease is mostly endemic in Latin America, with periodic
      occurrences of outbreaks and epidemics over the last few decades. This literature
      review summarizes the available epidemiological data for this region between 1945
      and 2010. Incidence rates and serogroup distribution differ from country to
      country and over time. Serogroups A, B, and C have all been major causes of
      meningococcal disease since the 1970s. In the last decade serogroups W135 and Y
      may now be emerging in certain countries, with serogroup A virtually
      disappearing. Although progress has been made in improving and coordinating the
      surveillance of invasive disease, the uniformity and quality of reported data
      reflect the fact that the current surveillance systems focus on passive rather
      than active reporting, hence the reliability of data may vary between countries.
      Consideration of vaccination policies to control meningococcal disease can only
      be made with a sufficient understanding of the changing epidemiology in the
      region.

PMID- 22877583
TI  - Intracellular carbonic anhydrase contributes to the red blood cell adrenergic
      response in rainbow trout Oncorhynchus mykiss.
AB  - In many teleost fish, catecholamines activate a red blood cell (RBC) Na+/H+
      exchanger (betaNHE), raising RBC intracellular pH to protect haemoglobin-O2
      loading. The present study tested the hypothesis that RBC intracellular carbonic
      anhydrase (CA) contributes to this adrenergic response. The pH of rainbow trout
      (Oncorhynchus mykiss) blood was monitored continuously in vitro using blood
      flowing in a semi-closed loop or in vivo using an extracorporeal circulation.
      Addition or injection of isoproterenol activated the betaNHE, causing blood pH to
      fall (in vitro DeltapH = -0.28+/-0.03 pH units, N=16; in vivo, -0.12+/-0.02 pH
      units, N=6). Both in vitro and in vivo, inhibition of RBC CA by acetazolamide
      significantly decreased the magnitude of the adrenergic response (in vitro,
      DeltapH=-0.22+/-0.02 pH units, N=16; in vivo, -0.02+/-0.01 pH units, N=6) as well
      as the rate of recovery of blood pH following the adrenergic response. These
      results support the hypothesis that RBC intracellular CA plays an important role
      in the RBC adrenergic response of rainbow trout, and fuel speculation that
      interspecific differences in RBC CA activity are associated with the magnitude of
      the RBC adrenergic response.

PMID- 22877582
TI  - The electrochemical surface forces apparatus: the effect of surface roughness,
      electrostatic surface potentials, and anodic oxide growth on interaction forces,
      and friction between dissimilar surfaces in aqueous solutions.
AB  - We present a newly designed electrochemical surface forces apparatus (EC-SFA)
      that allows control and measurement of surface potentials and interfacial
      electrochemical reactions with simultaneous measurement of normal interaction
      forces (with nN resolution), friction forces (with MUN resolution), and distances
      (with A resolution) between apposing surfaces. We describe three applications of
      the developed EC-SFA and discuss the wide-range of potential other applications.
      In particular, we describe measurements of (1) force-distance profiles between
      smooth and rough gold surfaces and apposing self-assembled monolayer-covered
      smooth mica surfaces; (2) the effective changing thickness of anodically growing
      oxide layers with A-accuracy on rough and smooth surfaces; and (3) friction
      forces evolving at a metal-ceramic contact, all as a function of the applied
      electrochemical potential. Interaction forces between atomically smooth surfaces
      are well-described using DLVO theory and the Hogg-Healy-Fuerstenau approximation
      for electric double layer interactions between dissimilar surfaces, which
      unintuitively predicts the possibility of attractive double layer forces between
      dissimilar surfaces whose surface potentials have similar sign, and repulsive
      forces between surfaces whose surface potentials have opposite sign. Surface
      roughness of the gold electrodes leads to an additional exponentially repulsive
      force in the force-distance profiles that is qualitatively well described by an
      extended DLVO model that includes repulsive hydration and steric forces.
      Comparing the measured thickness of the anodic gold oxide layer and the charge
      consumed for generating this layer allowed the identification of its chemical
      structure as a hydrated Au(OH)(3) phase formed at the gold surface at high
      positive potentials. The EC-SFA allows, for the first time, one to look at
      complex long-term transient effects of dynamic processes (e.g., relaxation
      times), which are also reflected in friction forces while tuning electrochemical
      surface potentials.

PMID- 22877584
TI  - Respiratory mechanics in COPD patients who failed non-invasive ventilation: role
      of intrinsic PEEP.
AB  - Non-invasive positive pressure ventilation (NPPV) is the first choice to treat
      exacerbations in COPD patients. NPPV can fail owing to different causes related
      to gas exchange impairment (RF group) or intolerance (INT group). To assess if
      the respiratory mechanical properties and the ratio between the dynamic and
      static intrinsic positive end-expiratory pressure (PEEP(i),dyn/PEEP(i),stat),
      reflecting lung mechanical inequalities, were different between groups, 29 COPD
      patients who failed NPPV (15 RF and 14 INT) were studied, early after the
      application of invasive ventilation. Blood gas analysis, clinical status, and
      mechanical properties were measured. pH was higher in INT patients before
      intubation (p<0.001). PEEP(i),dyn/PEEP(i),stat was found higher in INT group with
      (p=0.021) and without PEEP (ZEEP, p<0.01). PEEP(i),dyn/PEEP(i),stat was
      exponentially associated with the duration of NPPV in INT group (p=0.011). INT
      and RF patients had similar impairment of respiratory system resistance and
      elastance.

PMID- 22877585
TI  - Synthetic allergen design reveals the significance of moderate affinity epitopes
      in mast cell degranulation.
AB  - This study describes the design of a well-defined homotetravalent synthetic
      allergen (HTA) system to investigate the effect of hapten-IgE interactions on
      mast cell degranulation. A library of DNP variants with varying affinities for
      IgE(DNP) was generated (K(d) from 8.1 nM to 9.2 MUM), and 8 HTAs spanning this
      range were synthesized via conjugation of each DNP variant to the tetravalent
      scaffold. HTAs with hapten K(d) < 235 nM stimulated degranulation following a
      bell-shaped dose response curve with maximum response occurring near the hapten
      K(d). HTAs with hapten K(d) >= 235 nM failed to stimulate degranulation. To mimic
      physiological conditions, the percent of allergen specific IgE on cell surface
      was varied, and maximum degranulation occurred at 25% IgE(DNP). These results
      demonstrated that moderate hapten-IgE affinities are sufficient to trigger mast
      cell degranulation. Moreover, this study established the HTA design as a well
      defined, controllable, and physiologically relevant experimental system to
      elucidate the mast cell degranulation mechanism.

PMID- 22877586
TI  - Reconsolidation of memory: a decade of debate.
AB  - Memory consolidation refers to a slow process that stabilises a memory trace
      after initial acquisition of novel events. The consolidation theory posits that
      once a memory is stored in the brain, it remains fixed for the lifetime of the
      memory. However, compelling evidence has suggested that upon recall, memories can
      re-enter a state of transient instability, requiring further stabilisation to be
      available once again for recall. Since its rehabilitation in the past ten years,
      this process of reconsolidation of memory after recall stimulated intense debates
      in the field of cognitive neuroscience. In this review we compile this plentiful
      literature with a particular emphasis on some of the key questions that have
      emerged from the reconsolidation theory. We focus on tracing the characterisation
      of the boundary conditions that constrain the occurrence of memory
      reconsolidation. We also discuss accumulating evidence supporting the idea that
      reconsolidation, as implied by its definition, is not a mere repetition of
      consolidation. We review seminal studies that uncovered specific mechanisms
      recruited during reconsolidation that are not always crucially involved in
      consolidation. We next address the physiological significance of reconsolidation
      since several lines of evidence support the idea that reconsolidation, as opposed
      to consolidation, may offer a unique opportunity to update memories. We finally
      discuss recent evidence for or against the potential that the process of memory
      reconsolidation offers for ongoing efforts to develop novel strategies to combat
      pathogenic memories.

PMID- 22877587
TI  - A comparison of young women's actual and assigned timing of use of a microbicide
      surrogate.
AB  - PURPOSE: This study examined young women's actual timing of use of a microbicide
      surrogate gel (vaginal moisturiser (VM)) compared with assigned timing
      conditions. METHODS: Participants used a VM with coitus during 4-week cycles over
      a 3-year period in random timing sequences: 1h before coitus, 10 min before
      coitus and 10 min after coitus. Daily diaries collected information related to
      coital behaviours, VM use and timing, and participants' and partners' VM
      assessments. Descriptive and mixed-effects model analyses were conducted.
      RESULTS: At least three VM timing conditions were completed by 109 women aged 18
      22 years old. Of 17?772 diary days collected, coitus was reported on 2128 (1252
      with VM use; 59%). Median times between VM application and coitus were: 60 min
      before coitus (mean=68.2; s.d.=76.9) for the 1-h pre-coital group, 13.5 min
      before coitus (mean=44.9; s.d.=117.1) for the 10-min pre-coital group and 5 min
      before coitus (mean=24.5; s.d.=205.1) for the 10-min post-coital group. Women
      reported that the VM was very easy to use (68%), it was somewhat messy (61%),
      they were very wet during sex (81%), sex was very good (80%) and their partners
      liked using the VM (38%). CONCLUSIONS: Overall, the VM was rated positively.
      There was substantial deviation in application time across timing conditions,
      with significantly greater variability in the post-coital group. These findings
      contribute to understanding of how VMs are accepted and used, with implications
      for HIV prevention with microbicides requiring specific application timing.

PMID- 22877588
TI  - The effects of translating the Multidimensional Sexuality Questionnaire from
      English to Mandarin: a test of reliability and validity.
AB  - BACKGROUND: In China, sexuality studies using validated psychosexual instruments
      are limited, with no valid Mandarin language version of a sexuality inventory
      with psychometric properties available for use. Thus, the Mandarin version of the
      Multidimensional Sexuality Questionnaire (M-MSQ), comprising four subscales,
      originating from the Multidimensional Sexuality Questionnaire, was tested for its
      psychometric properties. METHODS: A convenience sampling technique was employed
      to recruit 200 oil workers (100 males and 100 females) in northern China.
      Originally, 158 participants (84 males and 74 females) completed the
      questionnaire; these accounted for 79% of the total study sample. From this
      group, a subsample of 50 participants (25 males and 25 females) was randomly
      selected to investigate the test-retest reliability. Of these, the responses of
      33 participants (18 males and 15 females) were valid. The analysis on reliability
      was based on Cronbach's alpha, Pearson's correlation coefficient (r) and the
      intraclass correlation coefficient, also including evaluation on criterion
      validity and discriminatory validity. RESULTS: The M-MSQ was found to be
      homogeneous in factor structure, comparing well with the original questionnaire.
      Both the discriminatory validity and the criterion-related validity were
      satisfactory in the total sample and gender groups, in addition, the overall
      reliability of the M-MSQ was sound in internal consistency with Cronbach's
      alpha=0.900-0.931. The results of the test-retest showed that the stability of
      the M-MSQ achieved a positive statistically significant standard assessed by
      Pearson's coefficient and the intraclass correlation coefficient. CONCLUSION: The
      M-MSQ is reliable in these four subscales, and may be used as a measure of sexual
      esteem, sexual conscious, sexual motivation and sexual satisfaction in Mandarin
      speakers.

PMID- 22877589
TI  - Perceived gender inequality, sexual communication self-efficacy, and sexual
      behaviour among female undergraduate students in the Mekong Delta of Vietnam.
AB  - BACKGROUND: Worldwide, the literature on sexual behaviour has documented
      associations between gender-based relationship inequality and sexual
      communication ability and the actual use of condoms or other contraceptives among
      young women. This study aimed to examine these associations among undergraduate
      female students in the Mekong Delta of Vietnam. METHODS: A cross-sectional survey
      of 1181 female third-year students from two universities in the Mekong Delta was
      conducted. Latent variable modelling and logistic regression were employed to
      examine the hypothesised associations. RESULTS: Among the 72.4% of students who
      had ever had boyfriends, 44.8% indicated that their boyfriends had asked for sex,
      13% had had penile-vaginal sex and 10.3% had had oral sex. For those who had had
      penile-vaginal sex, 33% did not use any contraceptive method, including condoms,
      during their first sexual intercourse. The greater a student's perception that
      women were subordinate to men, the lower her self-efficacy for sexual
      communication and the lower her actual frequency of discussing safer sex matters
      and asking her partner to use a condom. Sexual communication self-efficacy was
      associated with actual contraceptive use (P=0.039) but only marginally with
      condom use (P=0.092) at first sexual intercourse. CONCLUSION: Sexual health
      promotion strategies should address the influence of gender relations on young
      women's sexual communication self-efficacy and the subsequent impact on actual
      contraceptive and condom use.

PMID- 22877590
TI  - Knowledge, attitudes and behaviours of health care workers towards clients of
      sexual health services in Fiji.
AB  - A cross-sectional survey was conducted to identify the attitudes and behaviours
      of health care workers (HCWs) in health care settings (HCS) in Fiji involving 369
      participants. Self-rated knowledge of HIV and sexually transmissible infections
      (STIs) varied depending on whether the HCS was divisional or sub-divisional, and
      varied between the various national divisions. HCWs with experience in HIV,
      reproductive health and antenatal clinics had higher self-rated HIV knowledge. A
      high proportion had a fear of catching HIV from HIV-positive clients. This study
      found high levels of negative attitudes towards clients from vulnerable groups
      with regards to the transmission and spread of HIV. Study participants also
      reported observing differential treatment by their colleagues if a client was
      known to have or was suspected of having HIV. There is a need for further HIV
      education of HCWs, with training focussed on occupational risk, and on reducing
      stigma and discrimination of those living with or vulnerable to HIV in Fiji.

PMID- 22877591
TI  - Factors associated with unprotected anal intercourse and age among men who have
      sex with men who are gay bar customers in Osaka, Japan.
AB  - BACKGROUND: HIV infections among men who have sex with men (MSM) are increasing
      in Japan. METHOD: An anonymous self-administered questionnaire among clients of a
      gay bar in Osaka was used to analyse the relationship between age and unprotected
      anal sex (UAI). RESULTS: The highest rate of UAI was reported among those aged
      >=45 (73.3%), followed by the <=24 (60.7%), 25-34 (56.3%) and 35-44 (54.0%) age
      groups (P=0.01). In multivariate analysis, UAI was related to sex with six or
      more sexual partners among those aged <=24 (adjusted odds ratio (AOR), 4.88;
      confidence interval (CI), 1.21-19.74), bisexual identity (AOR, 2.47; CI, 1.06
      5.76) and drug use (AOR, 0.49; CI, 0.26-0.93 for no drug use) in the 25-34 age
      group, and no lifetime HIV testing in the 35-44 age group (AOR, 2.57; CI, 1.40
      4.74). Condom purchasing and condom carrying were protective of UAI in 25-34, 35
      44 and >=45 age groups. CONCLUSION: Programs promoting condom use are needed for
      younger and older MSM.

PMID- 22877592
TI  - Assessing spatial gaps in sexually transmissible infection services and
      morbidity: an illustration with Texas county-level data from 2007.
AB  - BACKGROUND: In the United States, sexually transmissible infection (STI) and
      family planning (FP) clinics play a major role in the detection and treatment of
      STIs. However, an examination of the spatial distribution of these service sites
      and their association with STI morbidity and county-level socioeconomic
      characteristics is lacking. We demonstrate how mapping and regression methods can
      be used to assess the spatial gaps between STI services and morbidity. METHODS:
      We used 2007 county-level surveillance data on chlamydia (Chlamydia trachomatis),
      gonorrhoea (Neisseria gonorrhoeae) and syphilis. The geocoded STI service (STI or
      FP clinic) locations overlaid on the Texas county-level chlamydia, gonorrhoea and
      syphilis morbidity map indicated that counties with high incidence had at least
      one STI service site. Logistic regression was used to examine the association
      between having STI services and county-level socioeconomic characteristics.
      RESULTS: Twenty-two percent of chlamydia high-morbidity counties (>365 out of
      100000); 32% of gonorrhoea high-morbidity counties (>136 out of 100000) and 23%
      of syphilis high-morbidity counties (>=4 out of 100000 and at least two cases)
      had no STI services. When we controlled for socioeconomic characteristics, high
      morbidity syphilis was weakly associated with having STI services. The percent of
      the population aged 15-24 years, the percent of Hispanic population, the crime
      rate and population density were significantly (P<0.05) associated with having
      STI services. CONCLUSION: Our results suggest that having an STI service was not
      associated with high morbidity. The methods used have demonstrated the utility of
      mapping to assess the spatial gaps that exist between STI services and demand.

PMID- 22877593
TI  - Sexual health professionals' evaluations of a prototype computer-based
      contraceptive planning intervention for adolescents: implications for practice.
AB  - BACKGROUND: This paper aims to demonstrate how an online planning intervention to
      enhance contraceptive and condom use among adolescents was viewed by sexual
      health professionals. It identifies feedback that has facilitated improvement of
      the intervention both in terms of potential effectiveness and sustainability in
      practice. The data illustrate how professionals' feedback can enhance
      intervention development. METHOD: Ten practitioners (two male; eight female)
      representing a range of roles in sexual health education and healthcare were
      given electronic copies of the prototype intervention. Interviews were conducted
      to elicit feedback. Transcripts of the interviews were subjected to thematic
      analysis. RESULTS: Practitioners provided positive feedback about the
      intervention content, use of on-line media, the validity of planning techniques
      and the inclusion of males in contraceptive planning. Issues with rapport
      building, trust, privacy, motivation, and time and resources were raised,
      however, and the promotion of condom carrying was contentious. CONCLUSIONS:
      Professionals' feedback provided scope for developing the intervention to meet
      practitioners' concerns, thus enhancing likely feasibility and acceptability in
      practice. Ways in which particular feedback was generalisable to wider theory
      based and online intervention development are explored. Some responses indicated
      that health practitioners would benefit from training to embed theory-based
      interventions into sexual health education and healthcare.

PMID- 22877594
TI  - Improvement in antenatal testing for sexually transmissible infections and blood
      borne viruses in Western Australian hospitals, 2007 to 2010.
AB  - OBJECTIVE: Antenatal testing for specified sexually transmissible infections
      (STIs) and blood-borne viruses (BBVs) is recommended by the Royal Australian and
      New Zealand College of Obstetricians and Gynaecologists (RANZCOG). In 2007, the
      Department of Health, Western Australia (DoHWA) issued an operational directive
      (OD) recommending universal testing for chlamydia and additional testing for
      women in the STI endemic regions of Western Australia (WA). To assess adherence
      to these guidelines, seven WA public hospitals were audited. DESIGN AND SETTING:
      Demographic details and testing information of the last 200 women who gave birth
      immediately before 30 June 2007 (baseline audit) and 30 June 2010 (follow-up
      audit) were obtained from each hospital's antenatal records. RESULTS: Data from
      2718 women who delivered at >=36 weeks' gestation were analysed (baselinen=1353;
      follow-upn=1365). Testing at the first antenatal visit in accordance with the
      guidelines improved over time (RANZCOG: 68-74%; chi(2)-test = 13.96, d.f.=1,
      P<0.001; DoHWA OD: 12-40%; chi(2)-test = 279.71, d.f.=1, P<0.001). Retesting at
      28-36 weeks' gestation in the STI endemic regions improved for chlamydia (3-10%;
      chi(2)-test = 17.40, d.f.=1, P<0.001) and gonorrhoea (3-7%; chi(2)-test=6.62,
      d.f.=1, P<0.05), but not for syphilis or HIV. Chlamydia prevalence was 3% and 8%
      among nonAboriginal and Aboriginal women, respectively. CONCLUSION: The
      proportion of women delivering in WA public hospitals who had antenatal STI and
      BBV tests improved after publication and promotion of the OD.

PMID- 22877595
TI  - Increasing chlamydia diagnoses but little change in hospitalisations for ectopic
      pregnancy and infertility among women in New South Wales from 2001 to 2008.
AB  - BACKGROUND: As genital chlamydia (Chlamydia trachomatis) notifications have
      increased in Australia, time trends in hospitalisations for ectopic pregnancy and
      female infertility between 2001 and 2008 in New South Wales (NSW), Australia, and
      their relationship to trends in chlamydia notifications in women were assessed.
      METHODS: Annual rates of chlamydia notification, and hospitalisations for female
      infertility or ectopic pregnancy in women aged 15-44 years in NSW were calculated
      using routinely collected data. Chlamydia notifications and hospital separations
      occurring within each year belonging to the same woman were linked using
      probabilistic linkage of identifiers so that multiple notifications and
      admissions for one woman in each calendar year were only counted once. RESULTS:
      From 2001 to 2008, the annual rate of chlamydia diagnoses in women increased from
      157 to 477 per 100000 population (P(trend)<0.001). Over the same period, the
      annual hospitalisation rate for women with an ectopic pregnancy decreased from
      14.3 to 12.6 per 1000 births (P(trend)<0.001). This decrease was mostly in women
      aged 25-44 years, with no appreciable fall in women aged 15-24 years
      (P(trend)=0.8). Meanwhile, the hospitalisation rate for women with infertility of
      female origin did not follow a consistent trend: between 2001 and 2008, it
      fluctuated between a low of 479 and a high of 554 per 10000 women who were
      seeking pregnancy. CONCLUSIONS: These trends in ectopic pregnancy and female
      infertility suggest that the large increase in chlamydia notifications may not
      reflect hospitalisations for these two proposed chlamydia-related sequelae.

PMID- 22877596
TI  - Promotion and uptake of a new online partner notification and retesting reminder
      service for gay men.
AB  - BACKGROUND: In 2006, two new innovative features were added to a website called
      WhyTest which provided HIV/sexually transmissable infection (STI) information for
      gay men. The features were the 'Tell them' service allowing visitors to forward
      anonymous e-postcard or short message services (SMS) to sexual partners who may
      have been exposed to an STI, and the 'Remind me' service allowing visitors to
      register for a 3-, 6- or 12-monthly SMS reminder for a sexual health check. We
      describe the uptake of the new website functionality, and recognition of a health
      promotion campaign conducted in January-June 2007 to promote these new features.
      METHODS: We used Poisson regression to assess trends in monthly partner
      notification messages and STI testing reminders sent in August 2007-June 2010. We
      also analysed 2007 Sydney Gay Community Periodic Survey data to measure recall of
      the campaign. RESULTS: A total of 7923 partner notification messages were sent in
      the period August 2007-June 2010, with a significant increasing trend in monthly
      messages sent (P<0001). Of the total messages sent, 7581 (96%) were by SMS and
      342 (4%) by e-postcards. A total of 1023 STI testing reminders were sent in the
      same period, with a significant increasing trend in monthly reminders sent
      (P<0.001); 516 reminders were by SMS (50.4%) and 507 by email (49.6%). The 2007
      Sydney Gay Community Periodic Survey showed that 55% of the 2342 participants
      recognised the WhyTest image in the campaign. CONCLUSION: There was high
      awareness of WhyTest campaign images and the SMS partner notification service was
      more popular than the e-postcard feature.

PMID- 22877597
TI  - Prevalence and associated factors of condom use during commercial sex by female
      sex workers who were or were not injecting drug users in China.
AB  - OBJECTIVES: We compared the prevalence of inconsistent condom use during
      commercial sex between female sex workers (FSWs) who did or did not inject drugs
      (FSW-IDUs and FSW-NIDUs) and investigated factors associated with this
      inconsistent use within these two groups. METHODS: Some 158 FSW-NIDUs recruited
      from sex work venues and 218 FSW-IDUs recruited via the snowball sampling method
      were interviewed anonymously. RESULTS: Only 16.5% of the FSW-IDUs and 51.3% of
      the FSW-NIDUs had used condoms consistently during commercial sex in the last
      month (odds ratio (OR)=0.19). Factors significantly associated with inconsistent
      condom use in both groups included: behavioural intention for condom use
      (adjusted odds ratio (AOR)=0.05 and 0.13), condom unavailability (AOR=4.77 and
      5.33), a perceived need to engage in unprotected sex if the client paid more
      (AOR=8.74 and 10.84) or insisted on demanding unprotected sex (AOR=19.78 and
      7.59), and submissive gender power (AOR=11.65 and 2.58). One factor, perceived
      susceptibility (AOR=2.64), was significant only among FSW-NIDUs, whereas
      perceived efficacy of condom use in preventing HIV transmission (AOR=0.08),
      perceptions that peer FSWs would not use condoms with clients (AOR=2.23), self
      hatred (AOR=2.25) and lack of social support (AOR=2.93) were significant only
      among FSW-IDUs. Injecting with used syringes was also associated with
      inconsistent condom use among FSW-IDUs (AOR=4.64). CONCLUSIONS: FSW-IDUs were
      more likely than FSW-NIDUs to possess the cognitive and psychosocial conditions
      associated with unprotected commercial sex. Interventions need to take these
      differences into account.

PMID- 22877598
TI  - University students' perceptions of environmental risks to infertility.
AB  - BACKGROUND: Canadian young adults may be at risk of future infertility due to the
      high incidence of sexually transmissible infections (STIs) in this population.
      Young adults' perceptions of environmental risks, including contaminants, STIs
      and lifestyle habits on infertility, have not been examined. We have therefore
      designed a qualitative study to explore risk perceptions, awareness and knowledge
      of common environmental risk factors for infertility in a multiethnic sample of
      young adults. METHODS: Semistructured interviews were carried out with 40
      university undergraduate students (16 men and 24 women) in Ottawa, Canada,
      followed by qualitative analysis of interview transcripts to identify major
      themes. RESULTS: The following broad themes described participants' risk
      perceptions about infertility and (1) environmental contaminants: knowledge gaps,
      media reports and negative perception of chemicals; (2) STIs: superficial
      understanding of their role in infertility, general awareness, associations with
      sexual behaviours and knowledge gaps; and (3) lifestyle: protective benefits of
      healthy lifestyle, dose or exposure effects for smoking and alcohol, and
      knowledge gaps. Students demonstrated a superficial understanding of
      environmental risks, at times relying on media reports and anecdotal information
      to support their beliefs. CONCLUSIONS: This next generation of potential
      infertility patients exhibits a general understanding of environmental risks to
      infertility; however, young adults are overly optimistic that healthy lifestyle
      behaviours will safeguard future fertility. STIs represent the most significant
      modifiable risk factors for this age group; a message that can be supported by
      sexual and reproductive health education and promotion with greater emphasis on
      the long-term outcomes of STIs, including infertility.

PMID- 22877599
TI  - Trends in testing and notification for genital gonorrhoea in a northern
      Australian district, 2004-2008.
AB  - BACKGROUND: The study aimed to examine the trends in notification and testing for
      genital gonorrhoea (Neisseria gonorrhoeae) in the Darwin Remote District of
      Northern Territory, Australia, between 2004 and 2008. METHODS: Using laboratory
      testing data and notification data, we calculated the annual sex- and age
      specific notification rates, testing rates and positivity rates, and examined
      their trends. A deterministic matching method was used to identify unique
      individuals tested in order to estimate the number of years out of five in which
      each individual was tested. The correlation between testing rates and
      notification rates was calculated. RESULTS: The notification rates for the 15-24
      year age group increased sharply from 2004 to 2005, and then trended downwards
      between 2005 and 2008, with a decrease of 48.2% in females and 59.9% in males. No
      evident trends were found in testing rates. The positivity rates for this age
      group decreased by 46.3% in females (from 8.9% to 4.8%), and by 70.4% in males
      (from 10.8% to 3.2%) between 2004 and 2008. Over 76% of the population in this
      age-group had been tested at least once during the study period. A moderate
      correlation was found between notification rates and testing rates in both sexes.
      CONCLUSIONS: There was a significant decreasing trend in the notification rate of
      gonorrhoea between 2005 and 2008, which was most probably due to a decrease in
      prevalence. This study demonstrates the importance and utility of population
      level testing data in understanding the epidemiology of common bacterial sexually
      transmissible infections such as gonorrhoea.

PMID- 22877600
TI  - Symptomatic Trichomonas vaginalis infection in the setting of severe
      nitroimidazole allergy: successful treatment with boric acid.
AB  - This report describes a patient with symptomatic Trichomonas vaginalis infection
      who was unable to tolerate nitroimidazole drugs because of severe
      hypersensitivity, for which desensitisation was not possible. Use of intravaginal
      clotrimazole, intravaginal paromomycin, intravaginal furazolidone, povidone
      iodine douches, and oral nitazoxanide were unsuccessful in eradicating the
      patient's T. vaginalis infection. A 2-month course of intravaginal topical boric
      acid subsequently achieved a complete symptomatic cure and the patient remained
      T. vaginalis wet prep- and culture-negative 60 days after treatment.

PMID- 22877601
TI  - Prevalence and predictors of chlamydia co-infection among patients infected with
      gonorrhoea at a sexual health clinic in Sydney.
AB  - Anogenital gonorrhoea (Neisseria gonorrhoeae) is commonly diagnosed at sexual
      health clinics by on-site microscopy. Whether to add anti-chlamydial therapy in
      such situations is unclear. The medical records of all patients diagnosed with
      gonorrhoea between May 2005 and April 2010 at RPA Sexual Health were reviewed. Of
      165 patients diagnosed with anogenital gonorrhoea, 27 (16.4%, 95% confidence
      interval (CI) 11.1-22.9%) were co-infected with chlamydia (Chlamydia
      trachomatis). Compared with those only infected with anogenital gonorrhoea, there
      was no correlation of anogenital gonorrhoea-chlamydia co-infection with any
      demographic, behavioural or clinical variables examined. Anti-chlamydial therapy
      should be considered for all patients with gram stain diagnosed anogenital
      gonorrhoea at the initial clinic visit.

PMID- 22877602
TI  - Would you self-collect swabs in a unisex toilet?

PMID- 22877604
TI  - The presence of HBV mRNA in the fertilized in vitro embryo of HBV patients
      confirms vertical transmission of HBV via the ovum.
AB  - This study aimed to confirm that vertical transmission of hepatitis B virus (HBV)
      can occur via the infected ovum. Specimens studied were obtained from discarded
      test-tube embryos from mothers with chronic HBV infection who had received in
      vitro fertilization treatment. Single-cell reverse transcriptase-polymerase chain
      reaction was used to detect HBV mRNA in the embryos. HBV mRNA was detected in the
      cleavage embryos of patients with chronic HBV infection, with a detection rate of
      13.2% (5/38). The level of serum HBV DNA was not related to the HBV mRNA
      positivity rates in embryos. In this study, HBV mRNA was detected in test-tube
      embryos from HBV-infected mothers who had received in vitro fertilization
      treatment. This confirms the theory of vertical transmission of HBV via the ovum,
      thereby providing an important theoretical basis for further study on the
      mechanism of HBV vertical transmission, influencing factors and blocking
      measures.

PMID- 22877605
TI  - Nonionic block copolymers assemble on the surface of protein bionanoparticle.
AB  - Efficient delivery of therapeutic proteins to a target site remains a challenge
      due to rapid clearance from the body. Here, we selected tobacco mosaic virus
      (TMV) as a model protein system to investigate the interactions between the
      protein and a nonionic block copolymer as a possible protecting agent for the
      protein. By varying the temperature, we were able to obtain core-shell structures
      based on hydrophobic interactions among PO blocks and noncovalent interactions
      between TMV and EO blocks. The protein-polymer interactions were characterized by
      dynamic light scattering and isothermal titration calorimetry. This study
      establishes principles for the possible design of clinically useful protein
      delivery systems.

PMID- 22877606
TI  - Who should receive calcium and vitamin D supplementation?
AB  - Combined calcium and vitamin D supplementation is recommended in the prevention
      and treatment of osteoporosis. Until recently, supplementation was perceived as
      harmless without adverse effects. However, recent meta-analyses have provided
      evidence suggesting that calcium supplements, whether or not in combination with
      vitamin D, may be associated with cardiovascular risks. Although this finding
      constitutes a safety signal that has to be taken seriously, these data have to be
      interpreted with some caution. Current data do not allow definite conclusions to
      be drawn, but require further independent confirmation, since in numerous large
      studies, combined calcium and vitamin D supplementation did not increase
      cardiovascular events, even in the most frail and elderly populations.
      Nevertheless, it seems appropriate to correct calcium deficiency preferably by
      enhancing dietary intake and to target supplementation on individuals at high
      risk of fracture or in whom calcium and vitamin D deficiency is highly prevalent.
      Other trials have shown an increased risk of falls and fractures with annual oral
      administration of high dose of vitamin D. Therefore, supplementation with more
      frequent, lower doses is preferred. Yet, the optimal dosing schedule is unknown
      and needs further study. In order to correct age-associated secondary
      hyperparathyroidism and to prevent osteoporotic fractures, a daily dose of 1,000
      1,200 mg calcium and 800 IU vitamin D is recommended in elderly or
      institutionalised people, patients with established osteoporosis and individuals
      on glucocorticoids.

PMID- 22877608
TI  - Highly viscous guar gum shifts dietary amino acids from metabolic use to
      fermentation substrate in domestic cats.
AB  - The present study evaluated the potential of affecting amino acid metabolism
      through intestinal fermentation in domestic cats, using dietary guar gum as a
      model. Apparent protein digestibility, plasma fermentation metabolites, faecal
      fermentation end products and fermentation kinetics (exhaled breath hydrogen
      concentrations) were evaluated. Ten cats were randomly assigned to either guar
      gum- or cellulose-supplemented diets, that were fed in two periods of 5 weeks in
      a crossover design. No treatment effect was seen on fermentation kinetics. The
      apparent protein digestibility (P= 0.07) tended to be lower in guar gum
      supplemented cats. As a consequence of impaired small-intestinal protein
      digestion and amino acid absorption, fermentation of these molecules in the large
      intestine was stimulated. Amino acid fermentation has been shown to produce high
      concentrations of acetic and butyric acids. Therefore, no treatment effect on
      faecal propionic acid or plasma propionylcarnitine was observed in the present
      study. The ratio of faecal butyric acid:total SCFA tended to be higher in guar
      gum-supplemented cats (P= 0.05). The majority of large-intestinal butyric acid is
      absorbed by colonocytes and metabolised to 3-hydroxy-butyrylcoenzyme A, which is
      then absorbed into the bloodstream. This metabolite was analysed in plasma as 3
      hydroxy-butyrylcarnitine, which was higher (P= 0.02) in guar gum-supplemented
      cats. In all probability, the high viscosity of the guar gum supplement was
      responsible for the impaired protein digestion and amino acid absorption. Further
      research is warranted to investigate whether partially hydrolysed guar gum is
      useful to potentiate the desirable in vivo effects of this fibre supplement.

PMID- 22877609
TI  - Zebrafish inner retina: local signals for spatial position, luminance, and color
      contrast.
AB  - The retina of the zebrafish (Danio rerio) provides an unusually favorable
      preparation for genetic and developmental studies of the retina. Although the
      retina has been studied extensively for two decades, the neuronal response of the
      inner retina is largely unknown. This report describes a prominent local field
      potential of the inner retina, the Proximal Negative Response (PNR). It is best
      evoked by small (100 MUm) precisely positioned spots of light and is exceedingly
      sensitive to negative luminance contrast. The polarity, waveform, and other
      properties of the PNR suggest that it arises primarily from ON-OFF neurons of the
      proximal retina. The dominant response to negative contrast and its enhancement
      by light adaptation is believed due to a dominant presynaptic input from OFF
      bipolar cells. Color contrast was investigated by analyzing responses to a green
      bar moving on green versus red backgrounds. Over an intermediate range of
      irradiance, the response to green on red was larger than the response to green on
      green, thereby providing evidence for the encoding of color contrast. The present
      findings complement the classic principle of color contrast for human vision
      known as Kirschmann's third law and bring to mind the view of Walls that color
      contrast may have been the driving force for the evolution of color vision in
      lower vertebrates. In sum, the PNR of zebrafish provides clear evidence for the
      encoding of color and luminance contrast in the inner retina. It exhibits the
      defining properties common to many other vertebrates, reinforcing the view that
      the zebrafish may further serve as a model for retinal function and that the PNR
      may provide a new approach for studies of development, genetics, and retinal
      degeneration in zebrafish.

PMID- 22877610
TI  - Molecular delineation of species in the coral holobiont.
AB  - The coral holobiont is a complex assemblage of organisms spanning a diverse
      taxonomic range including a cnidarian host, as well as various dinoflagellate,
      prokaryotic and acellular symbionts. With the accumulating information on the
      molecular diversity of these groups, binomial species classification and a
      reassessment of species boundaries for the partners in the coral holobiont is a
      logical extension of this work and will help enhance the capacity for comparative
      research among studies. To aid in this endeavour, we review the current
      literature on species diversity for the three best studied partners of the coral
      holobiont (coral, Symbiodinium, prokaryotes) and provide suggestions for future
      work on systematics within these taxa. We advocate for an integrative approach to
      the delineation of species using both molecular genetics in combination with
      phenetic characters. We also suggest that an a priori set of criteria be
      developed for each taxonomic group as no one species concept or accompanying set
      of guidelines is appropriate for delineating all members of the coral holobiont.

PMID- 22877611
TI  - The biology and ecology of black corals (Cnidaria: Anthozoa: Hexacorallia:
      Antipatharia).
AB  - Antipatharians, commonly known as black corals, are treasured by many cultures
      for medicinal purposes and to produce jewellery. Despite their economic and
      cultural importance, very little is known about the basic biology and ecology of
      black corals because most species inhabit deeper-water environments (>50m) which
      are logistically challenging to study. There has been a recent increase of
      studies focusing on antipatharians; however, these have not yet been
      comprehensively reviewed. This literature review seeks to summarize the available
      information on the biology and ecology of antipatharians. Although black corals
      occur throughout all oceans and from subtidal to abyssal depths, they are
      particularly common in tropical and subtropical regions at depths below 50m.
      Antipatharians are generally found in areas with hard substrates, low-light and
      strong currents. Under favourable conditions, some black coral species form dense
      aggregations to the point of becoming ecologically dominant. Zooplankton appears
      to be the major component of the diet of black corals, which feed as suspension
      feeders and use mucus and nematocysts to capture their prey. Previously
      categorized as azooxanthellate corals, recent research has revealed that many
      antipatharians appear capable of harbouring symbionts, but unlike other corals,
      dinoflagellates of the genus Symbiodinium are generally not important to the
      nutrition of black corals. Antipatharians reproduce through both sexual and
      asexual processes. In general, polyps and colonies are gonochoric, with
      fertilization and larval development likely occurring externally; however, to
      date antipatharian larvae have only been observed for a single species.
      Antipatharians are generally slow-growing and long-lived organisms with maximum
      longevities ranging from decades to millennia. Black corals are more abundant
      with depth, a pattern which has been hypothesized to avoid competition with
      obligate photosynthetic fauna. Additionally, antipatharians may compete for space
      by using sweeper tentacles and secondary metabolites. With the exception of a few
      predators such as gastropods and green sea turtles, antipatharians appear to be
      little impacted by predation. Like other corals, antipatharians can be habitat
      engineers of importance to a myriad of associated organisms including arthropods,
      annelids, echinoderms, mollusks, sponges and cnidarians, several of which are
      adapted to live exclusively on black corals. Given that most black coral species
      inhabit remote environments, our understanding of these organisms will depend on
      our ability to effectively sample and study them. Future collections,
      particularly in deeper waters (>50m), will be needed to determine whether
      antipatharian species have limited biogeographical distributions or whether this
      has simply been an artefact of low sampling efforts away from population centres
      and taxonomic uncertainties within this group. Additionally, biological and
      ecological studies require increased sample sizes because most information is
      currently derived from the examination of only a handful of specimens.

PMID- 22877612
TI  - Jellyfish life histories: role of polyps in forming and maintaining scyphomedusa
      populations.
AB  - Large population fluctuations of jellyfish occur over a variety of temporal
      scales, from weekly to seasonal, inter-annual and even decadal, with some regions
      of the world reported to be experiencing persistent seasonal bloom events. Recent
      jellyfish research has focussed on understanding the causes and consequences of
      these population changes, with the vast majority of studies considering the
      effect of changing environmental variables only on the pelagic medusa. But many
      of the bloom-forming species are members of the Scyphozoa with complex metagenic
      life cycles consisting of a sexually reproducing pelagic medusa and asexually
      reproducing benthic polyp. Recruitment success during the juvenile (planula,
      polyp and ephyrae) stages of the life cycle can have a major effect on the
      abundance of the adult (medusa) population, but until very recently, little was
      known about the ecology of the polyp or scyphistoma phase of the scyphozoan life
      cycle. The aim of this review is to synthesise the current state of knowledge of
      polyp ecology by examining (1) the recruitment and metamorphosis of planulae
      larvae into polyps, (2) survival and longevity of polyps, (3) expansion of polyp
      populations via asexual propagation and (4) strobilation and recruitment of
      ephyrae (juvenile medusae). Where possible, comparisons are made with the life
      histories of other bentho-pelagic marine invertebrates so that further inferences
      can be made. Differences between tropical and temperate species are highlighted
      and related to climate change, and populations of the same species (in particular
      Aurelia aurita) inhabiting different habitats within its geographic range are
      compared. The roles that polyps play in ensuring the long-term survival of
      jellyfish populations as well as in the formation of bloom populations are
      considered, and recommendations for future research are presented.

PMID- 22877613
TI  - Hearing in cetaceans: from natural history to experimental biology.
AB  - Sound is a primary sensory cue for most marine mammals, and this is especially
      true for cetaceans. To passively and actively acquire information about their
      environment, cetaceans have some of the most derived ears of all mammals, capable
      of sophisticated, sensitive hearing and auditory processing. These capabilities
      have developed for survival in an underwater world where sound travels five times
      faster than in air, and where light is quickly attenuated and often limited at
      depth, at night, and in murky waters. Cetacean auditory evolution has capitalized
      on the ubiquity of sound cues and the efficiency of underwater acoustic
      communication. The sense of hearing is central to cetacean sensory ecology,
      enabling vital behaviours such as locating prey, detecting predators, identifying
      conspecifics, and navigating. Increasing levels of anthropogenic ocean noise
      appears to influence many of these activities. Here, we describe the historical
      progress of investigations on cetacean hearing, with a particular focus on
      odontocetes and recent advancements. While this broad topic has been studied for
      several centuries, new technologies in the past two decades have been leveraged
      to improve our understanding of a wide range of taxa, including some of the most
      elusive species. This chapter addresses topics including how sounds are received,
      what sounds are detected, hearing mechanisms for complex acoustic scenes, recent
      anatomical and physiological studies, the potential impacts of noise, and
      mysticete hearing. We conclude by identifying emerging research topics and areas
      which require greater focus.

PMID- 22877614
TI  - Exhaled nitric oxide.
AB  - Nitric oxide (NO) is now considered an important biomarker for respiratory
      disease. Studies have confirmed that the fractional concentration of exhaled
      nitric oxide (FENO) is elevated in the airways of patients who have asthma in
      comparison with controls. The level of FENO correlates well with the presence and
      level of inflammation, and decreases with glucocorticoid treatment. NO has
      potential to be used not only as a diagnostic aid but also as a management tool
      for assessing severity, monitoring response to therapy, and gaining control of
      asthma symptoms. This article reviews the biology of NO and its role in
      respiratory disease.

PMID- 22877615
TI  - Exhaled breath condensate: an overview.
AB  - Exhaled breath condensate (EBC) is a promising source of biomarkers of lung
      disease. EBC may be thought of either as a body fluid or as a condensate of
      exhaled gas. There are 3 principal contributors to EBC: variable-sized particles
      or droplets that are aerosolized from the airway lining fluid, distilled water
      that condenses from gas phase out of the nearly water-saturated exhalate, and
      water-soluble volatiles that are exhaled and absorbed into the condensing breath.
      The nonvolatile constituents and the water-soluble volatile constituents are of
      particular interest. Several key issues are discussed in this article.

PMID- 22877616
TI  - Exhaled breath condensate pH assays.
AB  - Airway pH is central to the physiologic function and cellular biology of the
      airway. The causes of airway acidification include (1) hypopharyngeal gastric
      acid reflux with or without aspiration through the vocal cords, (2) inhalation of
      acid fog or gas (such as chlorine), and (3) intrinsic airway acidification caused
      by altered airway pH homeostasis in infectious and inflammatory disease
      processes. The recognition that relevant airway pH deviations occur in lung
      diseases is opening doors to new simple and inexpensive therapies. This
      recognition has resulted partly from the ability to use exhaled breath condensate
      as a window on airway acid-base balance.

PMID- 22877617
TI  - Asthma biomarkers in sputum.
AB  - Studies have shown that induced sputum can provide information regarding the
      cellular and molecular processes involved in asthma and other obstructive
      pulmonary diseases, and can aid in the diagnosis of asthma and in distinguishing
      asthma from chronic obstructive pulmonary disease in patients who present with
      evidence for fixed airflow obstruction. Sputum eosinophils are associated with
      both asthma severity and level of asthma control. By effectively treating sputum
      eosinophilia, the number of asthma exacerbations can be significantly reduced
      compared with managing asthma based on symptoms and lung function.

PMID- 22877618
TI  - Tissue-based and bronchoalveolar lavage-based biomarkers in asthma.
AB  - In this article, tissue and bronchoalveolar lavage biomarkers of asthma are
      evaluated for their use in asthma and evaluated in the context of the phenotype
      that they may best represent. It is hoped that studies that better link
      biomarkers to specific phenotypes will eventually improve the ability to evaluate
      genetic features, diagnose, measure progression, and tailor treatments. Although
      some biomarkers may only be associated with disease, it is also likely that some
      may be mechanistically involved. Some of these biomarkers may then also become
      targets for specific treatment.

PMID- 22877619
TI  - Bronchoprovocation testing in asthma.
AB  - This article covers the relationships between BHR and airway inflammation. Recent
      evidence suggests that various commonly used bronchoprovocation challenges (BPCs)
      differ in their potential to serve as inflammatory biomarkers. The response to
      direct stimuli depends on the smooth muscle's response to the chemical, whereas
      in indirect challenges, the reaction is caused by the smooth muscle's
      responsiveness to the mediators induced by the stimuli. The information obtained
      from studies with BPC has provided insights into the pathogenesis and
      pathophysiology of asthma, and the relationships between airway inflammation and
      bronchial hyper-responsiveness.

PMID- 22877620
TI  - Urinary leukotriene E4 as a biomarker of exposure, susceptibility and risk in
      asthma.
AB  - Measurement of urinary leukotriene E(4) (uLTE(4)) is a sensitive and noninvasive
      method of assaying total body cysteinyl leukotriene production and changes in
      cysteinyl leukotriene production. Recent studies have reported on novel uLTE(4)
      receptor interactions, and new applications for uLTE(4), as a biomarker of
      environmental exposure to tobacco smoke and ambient air pollution, a predictor of
      risk for asthma exacerbations related to tobacco smoke, and a marker of
      susceptibility to leukotriene receptor antagonists.

PMID- 22877621
TI  - Update on biomarkers in allergy and asthma. Preface.

PMID- 22877622
TI  - Biomarkers in asthma and allergy.

PMID- 22877623
TI  - Synthesis, characterization and pharmacological study of 4,5-dihydropyrazolines
      carrying pyrimidine moiety.
AB  - A series of 5-bromo-2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)pyrimidine were
      prepared under conventional heating as well as microwave reaction condition. The
      newly synthesized compounds were characterized on the basis of elemental,
      spectral and single crystal X-ray studies. These new compounds were screened for
      their antioxidant, anti-inflammatory and analgesic activities. Some of these
      compounds exhibited potent biological activities compared to the standard drug.

PMID- 22877624
TI  - Stoppa approach, an alternative for total hip arthroplasty in an intra-pelvic
      cup.
AB  - Removal of an acetabular prosthesis that has migrated into the pelvis can be
      hazardous. We describe the preoperative planning and the surgical procedure for
      removing a severely displaced acetabular component in one patient and outline our
      recommendation for the use of Stoppa approach because it has advantages of simple
      dissection, a low complication rate, and may help in preventing life-threatening
      problems.

PMID- 22877625
TI  - Differential effect of baclofen on cortical and spinal inhibitory circuits.
AB  - OBJECTIVE: The cutaneous silent period (SP) is a spinal inhibitory reflex, which
      suppresses activity in spinal motor nuclei. Transcranial magnetic stimulation
      (TMS) elicits a cortical SP, which represents GABA(B) receptor-mediated
      inhibition of cortical excitability. Baclofen as a strong GABA(B) agonist
      effectively reduces muscle hypertonia, however, it is not known whether
      intrathecal baclofen (ITB) may modulate spinal inhibitory circuits. METHODS: We
      evaluated clinical and neurophysiological effects of ITB in ten patients with
      severe spasticity due to spinal cord injury (n = 9) and chronic progressive
      multiple sclerosis (n = 1). Neurophysiological assessment included H reflex and
      cutaneous and cortical SPs, before and 15, 30, 60, 90, 120, and 180 min after ITB
      bolus administration. RESULTS: ITB suppressed soleus H reflex as early as 15 min
      after lumbar bolus injection; MAS scores declined after 1 h. Cortical SP end
      latency and duration increased progressively with a significant maximum 3h
      following ITB bolus, whereas cutaneous SP latency and duration did not change
      significantly. CONCLUSION: The present findings suggest that baclofen does not
      affect the cutaneous SP, but prolongs the cortical SP. SIGNIFICANCE: The spinal
      inhibitory circuitry of the cutaneous SP is not modulated by GABA(B) receptor
      mediated activity, in contrast to the cortical inhibitory circuitry of the
      cortical SP, which is subject to powerful GABA(B) control.

PMID- 22877626
TI  - Immune transcript variations among Aedes aegypti populations with distinct
      susceptibility to dengue virus serotype 2.
AB  - The innate immune response of insects is one of the factors that may dictate
      their susceptibility to viral infection. Two immune signaling pathways, Toll and
      JAK-STAT, and the RNA interference (RNAi) pathway are involved in Aedes aegypti
      responses against dengue virus (DENV), however natural differences in these
      antiviral defenses among mosquito populations have not been studied. Here, two
      field Ae. aegypti populations from distinct ecological environments, one from
      Recife and the other from Petrolina (Brazil), and a laboratory strain were
      studied for their ability to replicate a primary isolate of dengue virus serotype
      2 (DENV-2). Virus infectivity and replication were determined in insect tissues
      collected after viral exposure through reverse-transcription real time PCR (RT
      PCR). The expression of a transcript representing these defense mechanisms (Toll,
      JAK-STAT and RNAi) in the midgut and fat body was studied with RT-PCR to evaluate
      variations in innate immune mechanisms possibly employed against DENV. Analyses
      of infection rates indicated that the field populations were more susceptible to
      DENV-2 infection than the lab strain. There were distinct expression patterns
      among mosquito populations, in both control and infected insects. Moreover, lower
      expression of immune molecules in DENV-2-infected insects compared to controls
      was observed in the two field populations. These results suggest that natural
      variations in vector competence against DENV may be partly due to differences in
      mosquito defense mechanisms, and that the down-regulation of immune transcripts
      after viral infection depends on the insect strain.

PMID- 22877627
TI  - Is liposomal amphotericin B really safety in neonates?

PMID- 22877628
TI  - Fluorescence sensing of caffeine in aqueous solution with carbazole-based probe
      and imaging application in live cells.
AB  - The host-guest interaction of caffeine in aqueous solutions has been achieved by
      using carbazole based imino-phenol receptors with oxopurines influences their
      fluorescence properties and can be exploited for 'turn-ON' fluorescence sensing
      of caffeine. This new fluorescent probe with high sensitivity and selectivity for
      detection and first time imaging of caffeine in living cells was developed in
      aqueous media.

PMID- 22877629
TI  - 2-Phenylamino-6-cyano-1H-benzimidazole-based isoform selective casein kinase 1
      gamma (CK1gamma) inhibitors.
AB  - Screening of the Amgen compound library led to the identification of 2
      phenylamino-6-cyano-1H-benzimidazole 1a as a potent CK1 gamma inhibitor with
      excellent kinase selectivity and unprecedented CK1 isoform selectivity. Further
      structure-based optimization of this series resulted in the discovery of 1h which
      possessed good enzymatic and cellular potency, excellent CK1 isoform and kinase
      selectivity, and acceptable pharmacokinetic properties.

PMID- 22877630
TI  - Synthesis and structure-activity relationship of (1-halo-2-naphthyl) carbamate
      based inhibitors of KIAA1363 (NCEH1/AADACL1).
AB  - KIAA1363 is a serine hydrolase whose activity has been shown to be positively
      associated with tumor cell invasiveness. Thus, inhibitors of KIAA1363 represent a
      novel targeted therapy approach towards cancer. AX11890 ((1-bromo-2-naphthyl) N,N
      dimethylcarbamate) was identified as a KIAA1363 inhibitor with an IC(50) value of
      1.2 MUM and was shown using ESI-MS to carbamylate the catalytic residue Ser(191).
      SAR studies explored both substitution of the 1-bromo group and derivatization of
      the 6-position. Activity-based protein profiling demonstrated AX13057 inhibited
      tumor-localized KIAA1363 in SK-OV-3 xenograft-bearing mice.

PMID- 22877631
TI  - Combined receptor-based and ligand-based approach to delineate the mode of
      binding of guaianolide-endoperoxides to PfATP6.
AB  - Plasmodium falciparum calcium-ATPase (PfATP6) has been reported to be a target of
      artemisinin and related endoperoxides. In this study, a series of previously
      reported guaianolide-endoperoxides (thaperoxides) were docked into a homology
      model of PfATP6 and also used to develop a pharmacophore model. This combined
      approach led to useful insights into the binding determinants of thaperoxides to
      the malarial enzyme. In addition, in silico mutagenesis and molecular dynamics
      suggested the importance of Phe264 and the electrostatic interactions between
      Lys260 in helix H3 and Lys1036 and Asp1038 in L6/7 loop for the binding of
      thaperoxides. These results could help in the design of more potent inhibitors of
      PfATP6.

PMID- 22877632
TI  - Design of inhibitors of Helicobacter pylori glutamate racemase as selective
      antibacterial agents: incorporation of imidazoles onto a core
      pyrazolopyrimidinedione scaffold to improve bioavailabilty.
AB  - Structure-activity relationships are presented around a series of
      pyrazolopyrimidinediones that inhibit the growth of Helicobacter pylori by
      targeting glutamate racemase, an enzyme that provides d-glutamate for the
      construction of N-acetylglucosamine-N-acetylmuramic acid peptidoglycan subunits
      assimilated into the bacterial cell wall. Substituents on the inhibitor scaffold
      were varied to optimize target potency, antibacterial activity and in vivo
      pharmacokinetic stability. By incorporating an imidazole ring at the 7-position
      of scaffold, high target potency was achieved due to a hydrogen bonding network
      that occurs between the 3-position nitrogen atom, a bridging water molecule and
      the side chains Ser152 and Trp244 of the enzyme. The lipophilicity of the
      scaffold series proved important for expression of antibacterial activity.
      Clearances in vitro and in vivo were monitored to identify compounds with
      improved plasma stability. The basicity of the imidazole may contribute to
      increased aqueous solubility at lower pH allowing for improved oral
      bioavailability.

PMID- 22877633
TI  - Highly potent aminopyridines as Syk kinase inhibitors.
AB  - A novel class of potent Syk inhibitors has been developed from rational design.
      Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl
      motif and represented by compound 13b IC(50): 0.6 nM were identified.
      Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the
      central core provided diverse potent non-cytotoxic Syk inhibitors showing
      nanomolar activity inhibiting human mast cell line LAD2 degranulation.

PMID- 22877634
TI  - 2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal
      regulated kinase pathway and induces cell cycle arrest in human non-small lung
      carcinoma cells.
AB  - The anticancer potential of 2-amino-1,3,4-thiadiazole compounds has been
      documented by in vitro and in vivo studies. In our previous research, we
      described the synthesis as well as the antiproliferative and neuroprotective
      activities of 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole
      (FABT). The aim of the present study was to investigate the molecular mechanisms
      involved in FABT-induced growth inhibition in A549 lung carcinoma cells. Western
      blotting analysis revealed that FABT inhibited the activation of the
      extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and Real-time PCR
      analysis showed no changes in the expression of P44ERK1 and CREB1 genes.
      Furthermore, FABT induced cell cycle arrest in the GO/G1 phase and enhanced
      p27/Kip1 expression. Our results suggest that FABT acts by inhibiting ERK1/2
      pathway and cell cycle progression through G1 into S phase in A549 cells. Further
      studies are needed to completely explain the molecular mechanisms of anticancer
      action of this 2-aminothiadiazole derivative.

PMID- 22877635
TI  - Set-up of a new series of HDAC inhibitors: the 5,11-dihydrodibenzo[b,e]azepin-6
      ones as privileged structures.
AB  - We report here the strategy used in our research group to find a new class of
      histone deacetylase (HDAC) inhibitors. A series of 5,11
      dihydrodibenzo[b,e]azepine-6-ones alkylated on the amide nitrogen with an alkyl
      chain bearing an hydroxamic acids moiety at the end, has been designed (based
      upon the general motif for HDAC inhibitors), synthesized and tested. This allowed
      us to identify a new series of submicromolar HDAC inhibitors, which showed
      antiproliferative activity on HCT-116 colon carcinoma cells.

PMID- 22877636
TI  - Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90.
AB  - With structural guidance, tropane-derived HTS hits were modified to optimize for
      HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR
      development process 12i (XL888) was discovered and shown to reduce HSP90 client
      protein content in PD studies. Furthermore, efficacy experiments performed in a
      NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing
      regimens.

PMID- 22877637
TI  - Risk based microbiological criteria for Campylobacter in broiler meat in the
      European Union.
AB  - Quantitative microbiological risk assessment (QMRA) allows evaluating the public
      health impact of food safety targets to support the control of foodborne
      pathogens. We estimate the risk reduction of setting microbiological criteria
      (MCs) for Campylobacter on broiler meat in 25 European countries, applying
      quantitative data from the 2008 EU baseline survey. We demonstrate that risk
      based MCs can be derived without explicit consideration of Food Safety Objectives
      or Performance Objectives. Published QMRA models for the consumer phase and dose
      response provide a relation between Campylobacter concentration on skin samples
      and the attending probability of illness for the consumer. Probabilistic
      modelling is used to evaluate a set of potential MCs. We present the percentage
      of batches not complying with the potential criteria, in relation to the risk
      reduction attending totally efficient treatment of these batches. We find
      different risk estimates and different impacts of MCs in different countries,
      which offers a practical and flexible tool for risk managers to select the most
      appropriate MC by weighing the costs (i.e. non-compliant batches) and the
      benefits (i.e. reduction in public health risk). Our analyses show that the
      estimated percentage of batches not complying with the MC is better correlated
      with the risk estimate than surrogate risk measures like the flock prevalence or
      the arithmetic mean concentration of bacteria on carcasses, and would therefore
      be a good measure for the risk of Campylobacter on broiler meat in a particular
      country. Two uncertain parameters in the model are the ratio of within- and
      between-flock variances in concentrations, and the transition factor of skin
      sample concentrations to concentrations on the meat. Sensitivity analyses show
      that these parameters have a considerable effect on our results, but the impact
      of their uncertainty is small compared to that of the parameters defining the
      Microbiological Criterion and the concentration on the meat.

PMID- 22877638
TI  - Neuromechanical adaptation induced by jumping on an elastic surface.
AB  - Jumping on an elastic surface produces a number of sensory and motor adjustments.
      This effect caused by jumping on the trampoline has been called "trampoline
      aftereffect". The objective of the present study was to investigate the
      neuromuscular response related with this effect. A group of 15 subjects took part
      in an experimental session, where simultaneous biomechanical and
      electromyographic (EMG) recordings were performed during the execution of maximal
      countermovement jumps (CMJs) before and after jumping on an elastic surface. We
      assessed motor performance (leg stiffness, jump height, peak force, vertical
      motion of center of mass and stored and returned energy) and EMG activation
      patterns of the leg muscles. The results showed a significant increase (p <=
      0.05) of the RMS EMG of knee extensors during the eccentric phase of the jump
      performed immediately after the exposure phase to the elastic surface (CMJ(1)),
      and a significant increase (p <= 0.05) in the levels of co-activation of the
      muscles crossing the ankle joint during the concentric phase of the same jump.
      Results related with motor performance of CMJ(1) showed a significant increase in
      the leg stiffness (p <= 0.01) due to a lower vertical motion of center of mass
      (CoM) (p <= 0.005), a significant decrease in jump height (p <= 0.01), and a
      significantly smaller stored and returned energy (p <= 0.01). The changes found
      during the execution of CMJ(1) may result from a mismatch between sensory
      feedback and the efferent copy.

PMID- 22877639
TI  - Direct thrombin inhibitor-bivalirudin functionalized plasma polymerized
      allylamine coating for improved biocompatibility of vascular devices.
AB  - The direct thrombin inhibitor of bivalirudin (BVLD), a short peptide derived from
      hirudin, has drawn an increasing attention in clinical application because it is
      safer and more effective than heparin for diabetic patients with moderate- or
      high-risk for acute coronary syndromes (ACS). In this study, BVLD was covalently
      conjugated on plasma polymerized allylamine (PPAam) coated 316L stainless steel
      (SS) to develop an anticoagulant surface. QCM-D real time monitoring result shows
      that 565+/-20 ng/cm2 of BVLD was bound to the PPAam surface. Infrared
      spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) confirmed the
      immobilization of BVLD. The conjugation of BVLD onto the PPAam coating led to
      enhanced binding of thrombin, and the activity of the thrombin adsorbed on its
      surface was effectively inhibited. As a result, the BVLD immobilized PPAam (BVLD
      PPAam) substrate prolonged the clotting times, and exhibited inhibition in
      adhesion and activation of platelets and fibrinogen. We also found that the BVLD
      PPAam coating significantly enhanced endothelial cell adhesion, proliferation,
      migration and release of nitric oxide (NO) and secretion of prostaglandin I2
      (PGI2). In vivo results indicate that the BVLD-PPAam surface restrained thrombus
      formation by rapidly growing a homogeneous and intact endothelium on its surface.
      These data suggest the potential of this multifunctional BVLD-PPAam coating for
      the application not only in general vascular devices such as catheters, tubes,
      oxygenator, hemodialysis membranes but also vascular grafts and stents.

PMID- 22877640
TI  - Longevity and durability of atrioventricular valve repair in single-ventricle
      patients.
AB  - BACKGROUND: The durability of atrioventricular valve (AVV) repair and risk
      factors for recurrent AVV regurgitation (AVVR) and reintervention in single
      ventricle patients are not well defined. METHODS: Among 66 single-ventricle
      patients who underwent AVV repair between 1998 and 2011, 58 hospital survivors
      (88%) were retrospectively reviewed. Freedom from recurrent AVVR and
      reintervention were analyzed with Kaplan-Meier analysis. Predictors for recurrent
      AVVR, ventricular dysfunction, and reintervention were analyzed using regression
      analysis. RESULTS: Significant (more than mild+) AVVR developed in 47 patients
      (81%) during mean follow-up of 37 months (range, 0.2 to 103 months). Freedom from
      significant AVVR was 23.8% at 1 year and 16.9% at 5 years. Reintervention was
      performed in 12 patients (26%) at a mean of 24 months (range, 2 to 64 months)
      after the initial repair. Freedom from reintervention was 92.3% at 1 year and
      75.3% at 5 years. There were 11 late deaths (19%). Predictors for recurrent AVVR
      included repair at stage II (p=0.020) and cardiopulmonary bypass time (p=0.014).
      Predictors for reintervention included valvuloplasty as a repair technique
      (p=0.013), cardiopulmonary bypass time (p=0.002), aortic cross-clamp time
      (p=0.003), and significant residual intraoperative AVVR (p=0.012). Intraoperative
      ventricular dysfunction (p<0.001), aortic cross-clamp time (p=0.005), and cleft
      as the mechanism of regurgitation (p=0.023) predicted postrepair ventricular
      dysfunction. CONCLUSIONS: Although significant AVVR developed in most patients
      within 1 year of repair, the need for repeat valve repair is relatively low if
      ventricular function is preserved. Ventricular function after repair did not
      predict late survival but was related to the longevity of AVV competence and
      subsequent risk for reintervention.

PMID- 22877641
TI  - Peripheral facial nerve lesions induce changes in the firing properties of
      primary motor cortex layer 5 pyramidal cells.
AB  - Facial nerve lesions elicit long-lasting changes in vibrissal primary motor
      cortex (M1) muscular representation in rodents. Reorganization of cortical
      representation has been attributed to potentiation of preexisting horizontal
      connections coming from neighboring muscle representation. However, changes in
      layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet
      been explored. To do so, the effect of irreversible facial nerve injury on
      electrophysiological properties of layer 5 pyramidal neurons was characterized.
      Twenty-four adult male Wistar rats were randomly subjected to two experimental
      treatments: either surgical transection of mandibular and buccal branches of the
      facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of
      vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia
      was compared between sham-operated and facial nerve-injured animals. Injured
      animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery
      before recording in order to characterize the evolution of changes in
      electrophysiological activity. As compared to control, facial nerve-injured
      animals displayed the following sustained and significant changes in spontaneous
      activity: increased basal firing frequency, decreased spike-associated local
      field oscillation amplitude, and decreased spontaneous theta burst firing
      frequency. Significant changes in evoked-activity with whisker pad stimulation
      included: increased short latency population spike amplitude, decreased long
      latency population oscillations amplitude and frequency, and decreased peak
      frequency during evoked single-unit burst firing. Taken together, such changes
      demonstrate that peripheral facial nerve lesions induce robust and sustained
      changes of layer 5 pyramidal neurons in vibrissal motor cortex.

PMID- 22877642
TI  - A preliminary phylogeny of the genus Cunila D. Royen ex L. (Lamiaceae) based on
      ITS rDNA and trnL-F regions.
AB  - Cunila species are aromatic and medicinal plants commonly employed in folk
      medicine. This genus is distributed in North America and in southern South
      America. The species that occur in southern South America are classified into
      three botanical sections: Incanae, Incisae and Spicatae. The present study uses a
      phylogenetic approach to study the genetic relationship among the South and North
      American Cunila species, aiming to test the monophyly of the genus in its
      traditional circumscription. The results based on sequencing from nuclear (ITS
      rDNA) and chloroplast (trnL-F) sets did not agree with the traditional
      circumscription of the genus. These data, based on maximum parsimony, maximum
      likelihood and Bayesian analyses, point to the non-monophyletic status of Cunila,
      since the genus was separated into three segregated clades: (1) A South American
      subshrub clade formed by the species of the botanical section Spicatae, (2) a
      South American shrub clade that includes the species of the botanical sections
      Incanae and Incisae, and (3) a North American Cunila clade.

PMID- 22877643
TI  - The phylogenetic position of some Philippine "babblers" spans the muscicapoid and
      sylvioid bird radiations.
AB  - The Philippines is characterized by a high rate of endemism among its terrestrial
      vertebrates, including enigmatic genera with uncertain affinities. In a recent
      comprehensive study of the avian family of Timaliidae (babblers), it was shown
      that three putative babbler genera endemic to the Philippines (Leonardina,
      Robsonius, and Micromacronus) are distant relatives of Timaliidae. With
      additional DNA sequences from new samples and data from Genbank, we attempt to
      determine the phylogenetic affinities of these three genera and examine the
      resulting implications for biogeography and avian endemism in the Philippines.
      Well-supported phylogenies recover the three genera in three different families
      spanning the sylvioid and muscicapoid radiations of passerine birds. Leonardina
      groups with Muscicapidae and is most closely related to other isolated montane
      endemic species in Southeast Asia. Robsonius appears to be an early offshoot of
      Locustellidae. Micromacronus belongs in Cisticolidae, but its position in the
      family is unresolved. Contrary to implications based on traditional taxonomy, the
      Philippine archipelago appears to have played a minor role in the diversification
      of babblers.

PMID- 22877644
TI  - Exploring generic delimitation within the fern family Thelypteridaceae.
AB  - Thelypteridaceae is one of the largest families of polypodioid ferns. The generic
      classification of the family is still controversial because of high levels of
      convergent or parallel evolution of morphological characters and a lack of
      molecular phylogenetic studies. In the present study, phylogenetic analyses of
      three chloroplast regions (rbcL, rps4 and trnL-trnF intergenic spacer region) for
      115 taxa, representing 27 recognized segregates in the family, were conducted to
      explore infrafamilial relationships and gain further understanding of generic
      boundaries. The phylogenetic reconstructions resolved six distinct clades (Clade
      I-VI) with strong support. Seven genera: Cyclogramma, Macrothelypteris,
      Oreopteris, Phegopteris, Pseudophegopteris, Stegnogramma, and Thelypteris are
      recognized from Clades I, II, IV, and V. In Clade III, Metathelypteris was
      supported as monophyletic, but the other segregates Amauropelta, Coryphopteris,
      and Parathelypteris were polyphyletic or paraphyletic, preventing clear
      recognition of generic boundaries within this clade without additional sampling.
      Considering great morphological homoplasy within Clade VI, a large genus
      Cyclosorus is recognized to comprise several small recognized segregates. Within
      this clade, Pronephrium, and Christella were revealed to be polyphyletic, but
      several Asian-endemic segregates, such as Glaphyropteridopsis, Mesopteris, and
      Pseudocyclosorus were strongly supported as monophyletic. Analyses of the
      evolution of morphological character states on the molecular phylogeny showed
      extremely high levels of homoplastic evolution for many diagnostic characters.

PMID- 22877645
TI  - Molecular phylogeny and character evolution in terete-stemmed Andean opuntias
      (Cactaceae-Opuntioideae).
AB  - The cacti of tribe Tephrocacteae (Cactaceae-Opuntioideae) are adapted to diverse
      climatic conditions over a wide area of the southern Andes and adjacent lowlands.
      They exhibit a range of life forms from geophytes and cushion-plants to dwarf
      shrubs, shrubs or small trees. To confirm or challenge previous morphology-based
      classifications and molecular phylogenies, we sampled DNA sequences from the
      chloroplast trnK/matK region and the nuclear low copy gene phyC and compared the
      resulting phylogenies with previous data gathered from nuclear ribosomal DNA
      sequences. The here presented chloroplast and nuclear low copy gene phylogenies
      were mutually congruent and broadly coincident with the classification based on
      gross morphology and seed micro-morphology and anatomy. Reconstruction of
      hypothetical ancestral character states suggested that geophytes and cushion
      forming species probably evolved several times from dwarf shrubby precursors. We
      also traced an increase of embryo size at the expense of the nucellus-derived
      storage tissue during the evolution of the Tephrocacteae, which is thought to be
      an evolutionary advantage because nutrients are then more rapidly accessible for
      the germinating embryo. In contrast to these highly concordant phylogenies,
      nuclear ribosomal DNA data sampled by a previous study yielded conflicting
      phylogenetic signals. Secondary structure predictions of ribosomal transcribed
      spacers suggested that this phylogeny is strongly influenced by the inclusion of
      paralogous sequence probably arisen by genome duplication during the evolution of
      this plant group.

PMID- 22877646
TI  - Molecular phylogeny of the Entomophthoromycota.
AB  - The Entomophthoromycota is a ubiquitous group of fungi best known as pathogens of
      a wide variety of economically important insect pests, and other soil
      invertebrates. This group of fungi also includes a small number of parasites of
      reptiles, vertebrates (including humans), macromycetes, fern gametophytes, and
      desmid algae, as well as some saprobic species. Here we report on recent studies
      to resolve the phylogenetic relationships within the Entomophthoromycota and to
      reliably place this group among other basal fungal lineages. Bayesian
      Interference (BI) and Maximum Likelihood (ML) analyses of three genes (nuclear
      18S and 28S rDNA, mitochondrial 16S, and the protein-coding RPB2) as well as non
      molecular data consistently and unambiguously identify 31 taxa of
      Entomophthoromycota as a monophyletic group distinct from other Zygomycota and
      flagellated fungi. Using the constraints of our multi-gene dataset we constructed
      the most comprehensive rDNA phylogeny yet available for Entomophthoromycota. The
      taxa studied here belong to five distinct, well-supported lineages. The
      Basidiobolus clade is the earliest diverging lineage, comprised of saprobe
      species of Basidiobolus and the undescribed snake parasite Schizangiella
      serpentis nom. prov. The Conidiobolus lineage is represented by a paraphyletic
      grade of trophically diverse species that include saprobes, insect pathogens, and
      facultative human pathogens. Three well supported and exclusively
      entomopathogenic lineages in the Entomophthoraceae center around the genera
      Batkoa, Entomophthora and Zoophthora, although several genera within this crown
      clade are resolved as non-monophyletic. Ancestral state reconstruction suggests
      that the ancestor of all Entomophthoromycota was morphologically similar to
      species of Conidiobolus. Analyses using strict, relaxed, and local molecular
      clock models documented highly variable DNA substitution rates among lineages of
      Entomophthoromycota. Despite the complications caused by different rates of
      molecular evolution among lineages, our dating analysis indicates that the
      Entomophthoromycota originated 405+/-90 million years ago. We suggest that
      entomopathogenic lineages in Entomophthoraceae probably evolved from saprobic or
      facultatively pathogenic ancestors during or shortly after the evolutionary
      radiation of the arthropods.

PMID- 22877647
TI  - Benefit of an integrative psychotherapeutic nursing home program to reduce
      multiple psychiatric symptoms of psychogeriatric patients and caregiver burden
      after six months of follow-up: a re-analysis of a randomized controlled trial.
AB  - BACKGROUND: In this paper, we aim to test the long-term benefit of an integrative
      reactivation and rehabilitation (IRR) program compared to usual care in terms of
      improved psychogeriatric patients on multiple psychiatric symptoms (MPS) and of
      caregivers on burden and competence. Improvement was defined as >30% improvement
      (>= a half standard deviation) compared to baseline. METHODS: We used the
      following outcome variables: difference in the number of improved patients on MPS
      (Neuropsychiatric Inventory, NPI) and improved caregivers on burden (Caregiver
      Burden, CB) and competence (Caregiver Competence List, CCL). Assessments were
      taken after intake (T1) and after six months of follow-up (T3). Risk ratios (RR),
      number needed to treat (NNT), and odds ratios (ORs) were calculated. RESULTS: IRR
      had a significant positive effect on NPI-cluster hyperactivity (RR 2.64; 95% CI:
      1.26-5.53; NNT 4.07). In the complete cases analysis, IRR showed significant ORs
      of 2.80 on the number of NPI symptoms and 3.46 on the NPI-sum-severity; up to 76%
      improved patients. For caregivers, competence was a significant beneficiary in
      IRR (RR 2.23; 95% CI: 1.07-4.62; NNT 5.07). In the complete cases analysis, the
      ORs were significantly in favor of IRR on general burden and competence (ORs
      range: 2.40-4.18), with up to 71% improved caregivers. CONCLUSION: IRR showed a
      significantly higher probability of improvement with a small NNT of four on
      multiple psychiatric symptoms in psychogeriatric patients. The same applies to
      the higher probability to improve general burden and competence of the caregiver
      with an NNT of five. The results were even more pronounced for those who fully
      completed the IRR program. (Inter)national psychogeriatric nursing home care and
      ambulant care programs have to incorporate integrative psychotherapeutic
      interventions.

PMID- 22877648
TI  - The high glucose-induced stimulation of B1R and B2R expression via CB(1)R
      activation is involved in rat podocyte apoptosis.
AB  - AIMS: We examined renal kallikrein-kinin system (KKS) apoptosis and its related
      signaling pathway in rat podocytes. In addition, we studied the relationship of
      cannabinoid receptor 1 (CB(1)R) with high glucose and BK receptors. MAIN METHODS:
      Cell viability was determined by an MTT assay and apoptosis by DNA fragmentation
      assay, while gene expression was investigated by RT-PCR. Protein expression was
      analyzed by Western blot analysis. A chemical inhibitor or siRNA transfection was
      used to inhibit B1R, B2R, and CB(1)R signaling. KEY FINDINGS: High glucose (25
      mM) treatment decreased cell viability and increased DNA fragmentation. High
      glucose-induced DNA fragmentation and PARP and caspase-3 activations were blocked
      by both [des-Arg(10)]-HOE 140 (a B1R antagonist) and HOE 140 (a B2R antagonist).
      High glucose also increased Akt phosphorylation, ER stress-related protein
      expression, and NF-kappaB/I-kappaB phosphorylation in podocytes, which was
      blocked by both [des-Arg(10)]-HOE 140 and HOE 140. In addition, B1R and B2R siRNA
      transfections prevented high glucose-induced Akt and NF-kappaB activations in rat
      podocytes. Moreover, AM251 (a CB(1)R antagonist) treatment and CB(1)R siRNA
      transfection blocked the high glucose-induced stimulation of BK receptor
      expression, Akt activation, and NF-kappaB activation. SIGNIFICANCE: Our study
      suggests that hyperglycemia induces apoptosis via the stimulation of B1R and B2R
      expression through CB(1)R activation in rat podocytes in vitro, which is
      associated with the development of diabetic nephropathy.

PMID- 22877649
TI  - Beta-catenin mediates the apoptosis induction effect of celastrol in HT29 cells.
AB  - AIM: We evaluated the apoptosis induction effects of celastrol in human
      colorectal cancer cell line HT29 in WNT/beta-catenin pathway. MAIN METHODS: HT29
      cells were treated with various concentrations (10-100MUM) for 24h, MTT assay was
      performed to examine the effect of celastrol on growth inhibition of HT29 cells.
      Beta-catenin siRNA was used for transfection of cells. Cell apoptosis was
      detected through both DNA laddering analysis and Tdt-mediated dUTP nick end
      labeling (TUNEL) assay. Western blot analysis and real-time reverse transcription
      polymerase chain reaction technologies were applied to assess the expression
      level of c-Myc, Bax, and Bcl-2 in HT29 cells. KEY FINDINGS: Treatment of HT29
      cells with celastrol resulted in a growth inhibition effect, and the IC(50) value
      was 56MUM. Celastrol induced HT29 cells apoptosis, and increased the nuclear
      translocation of beta-catenin. Apoptosis induction effects of celastrol were
      significantly attenuated by beta-catenin siRNA transfection. Beta-catenin siRNA
      markedly increased mRNA and protein levels of c-Myc compared with control siRNA.
      Beta-catenin siRNA significantly inhibited the expression of Bax and Bcl-2 in
      celastrol-treated HT29 cells. SIGNIFICANCE: Beta-catenin mediates the apoptosis
      induction effects of celastrol in HT29 cells.

PMID- 22877651
TI  - Cannabidiol treatment ameliorates ischemia/reperfusion renal injury in rats.
AB  - AIMS: To investigate the protective effect of cannabidiol, the major non
      psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in
      rats. MAIN METHODS: Bilateral renal ischemia was induced for 30 min followed by
      reperfusion for 24h. Cannabidiol (5mg/kg, i.v.) was given 1h before and 12h
      following the procedure. KEY FINDINGS: Ischemia/reperfusion caused significant
      elevations of serum creatinine and renal malondialdehyde and nitric oxide levels,
      associated with a significant decrease in renal reduced glutathione. Cannabidiol
      significantly attenuated the deterioration in the measured biochemical parameters
      induced by ischemia/reperfusion. Histopathological examination showed that
      cannabidiol ameliorated ischemia/reperfusion-induced kidney damage.
      Immunohistochemical analysis revealed that cannabidiol significantly reduced the
      expression of inducible nitric oxide synthase, tumor necrosis factor-alpha,
      cyclooxygenase-2, nuclear factor-kappaB, Fas ligand and caspase-3, and increased
      the expression of survivin in ischemic/reperfused kidney tissue. SIGNIFICANCE:
      Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent
      a potential therapeutic option to protect against ischemia/reperfusion renal
      injury.

PMID- 22877650
TI  - Drosophila TRP channels and animal behavior.
AB  - Multiple classes of cell surface receptors and ion channels participate in the
      detection of changes in environmental stimuli, and thereby influence animal
      behavior. Among the many classes of ion channels, Transient Receptor Potential
      (TRP) cation channels are notable in contributing to virtually every sensory
      modality, and in controlling a daunting array of behaviors. TRP channels appear
      to be conserved in all metazoan organisms including worms, insects and humans.
      Flies encode 13 TRPs, most of which are expressed and function in sensory
      neurons, and impact behaviors ranging from phototaxis to thermotaxis, gravitaxis,
      the avoidance of noxious tastants and smells and proprioception. Multiple
      diseases result from defects in TRPs, and flies provide an excellent animal model
      for dissecting the mechanisms underlying "TRPopathies." Drosophila TRPs also
      function in the sensation of botanically derived insect repellents, and related
      TRPs in insect pests are potential targets for the development of improved
      repellents to combat insect-borne diseases.

PMID- 22877652
TI  - Androgen receptor repression of gonadotropin-releasing hormone gene transcription
      via enhancer 1.
AB  - Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic
      pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated
      by gonadal steroid hormones. Disruptions in androgen levels are involved in a
      number of reproductive defects, including hypogonadotropic hypogonadism and
      polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo
      and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone
      (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites
      in the proximal promoter. In this study, we show AR also represses GnRH
      transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766
      region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791,
      resulted in decreased basal activity and a loss of AR-mediated repression. AR
      bound to the -1796/-1791 sequence in electrophoretic mobility shift assays,
      indicating a direct interaction with DNA or other transcription factors in this
      region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive
      regions, including the site at -1792/-1791.

PMID- 22877654
TI  - Ten common questions (and their answers) about off-label drug use.
AB  - The term off-label drug use (OLDU) is used extensively in the medical literature,
      continuing medical education exercises, and the media. Yet, we propose that many
      health care professionals have an underappreciation of its definition,
      prevalence, and implications. This article introduces and answers 10 questions
      regarding OLDU in an effort to clarify the practice's meaning, breadth of
      application, acceptance, and liabilities. Off-label drug use involves prescribing
      medications for indications, or using a dosage or dosage form, that have not been
      approved by the US Food and Drug Administration. Since the Food and Drug
      Administration does not regulate the practice of medicine, OLDU has become
      common. It occurs in every specialty of medicine, but it may be more common in
      areas of medicine in which the patient population is less likely to be included
      in clinical trials (eg, pediatric, pregnant, or psychiatric patients).
      Pharmaceutical companies are not allowed to promote their medications for an off
      label use, which has lead to several large settlements for illegal marketing. To
      limit liability, physicians should prescribe medications only for indications
      that they believe are in the best interest of the patient. In addition, health
      care professionals should educate themselves about OLDU to weigh the risks and
      benefits and provide the best possible care for their patients.

PMID- 22877656
TI  - How rod, cone, and melanopsin photoreceptors come together to enlighten the
      mammalian circadian clock.
AB  - In mammals, a small number of retinal ganglion cells express melanopsin, an opsin
      photopigment, allowing them to be directly photoreceptive. A major function of
      these so-called intrinsically photosensitive retinal ganglion cells (ipRGCs) is
      to synchronize (entrain) endogenous circadian clocks to the external light:dark
      cycle. Thanks to their intrinsic light response, ipRGCs can support
      photoentrainment even when the other retinal photoreceptors (rods and cones) are
      absent or inactive. However, in the intact retina the ipRGC light response is a
      composite of extrinsic (rod/cone) and intrinsic (melanopsin) influences. As a
      result all three photoreceptor classes contribute to the retinal pathways
      providing light information to the clock. Here, we consider what each
      photoreceptor type contributes to the clock light response. We review
      electrophysiological and behavioral data pertinent to this question, primarily
      from laboratory rodents, drawing them together to provide a conceptual model in
      which each photoreceptor class plays a distinct role in encoding the light
      environment. We finally use this model to highlight some of the important
      outstanding questions in this field.

PMID- 22877655
TI  - Umbilical cord PUFA are determined by maternal and child fatty acid desaturase
      (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children
      (ALSPAC).
AB  - Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for
      brain growth and visual and cognitive development and is provided by materno
      fetal placental transfer. We recently showed that maternal fatty acid desaturase
      (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS
      genotypes influence the amounts of umbilical cord fatty acids has not been
      investigated until now. The aim of the present study was to investigate the
      influence of maternal and child FADS genotypes on the amounts of LC-PUFA in
      umbilical cord venous plasma as an indicator of fetal fatty acid supply during
      pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed
      for association with seventeen FADS gene cluster SNP in over 2000 mothers and
      children from the Avon Longitudinal Study of Parents and Children. In a
      multivariable analysis, the maternal genotype effect was adjusted for the child
      genotype and vice versa to estimate which of the two has the stronger influence
      on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes
      influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically,
      most analysed maternal SNP were associated with cord plasma levels of the
      precursor n-6 PUFA, whereas the child genotypes were mainly associated with more
      highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty
      acids suggests that fetal LC-PUFA status is determined to some extent by fetal
      fatty acid conversion. Associations of particular haplotypes suggest specific
      effects of SNP rs498793 and rs968567 on fatty acid metabolism.

PMID- 22877657
TI  - Melanopsin phototransduction: slowly emerging from the dark.
AB  - Melanopsin expressing retinal ganglion cells represent a third class of ocular
      photoreceptors and are involved in irradiance detection and non-image-forming
      responses to light including pupil constriction, circadian entrainment, and
      regulation of sleep. Over recent years, there has been a rapid increase in our
      understanding of the anatomical variety of pRGC subtypes, the regions of the
      brain which they innervate, and the behavioral responses of melanopsin-based
      light detection. However, by contrast, our understanding of the intracellular
      signaling cascade initiated following activation of melanopsin has, until
      recently, remained poorly characterized. This chapter focus on the melanopsin
      signaling pathway, detailing the cellular mechanisms of phototransduction that
      occur within pRGCs, highlighting recent advances, but also the gaps in our
      understanding of this important light detecting system.

PMID- 22877658
TI  - Circadian clocks: lessons from fish.
AB  - Our understanding of the molecular and cellular organization of the circadian
      timing system in vertebrates has increased enormously over the past decade. In
      large part, progress has been based on genetic studies in the mouse as well as on
      fundamental similarities between vertebrate and Drosophila clocks. The zebrafish
      was initially considered as a potentially attractive genetic model for
      identifying vertebrate clock genes. However, instead, fish have ultimately proven
      to be valuable complementary models for studying various aspects of clock
      biology. For example, many fish can shift from diurnal to nocturnal activity
      implying specific flexibility in their clock function. We have learned much about
      the function of light input pathways, and the ontogeny and function of the pineal
      organ, the fish central pacemaker. Finally, blind cavefish have also provided new
      insight into the evolution of the circadian clock under extreme environmental
      conditions.

PMID- 22877659
TI  - Two clocks in the brain: an update of the morning and evening oscillator model in
      Drosophila.
AB  - Circadian clocks play an essential role in adapting the activity rhythms of
      animals to the day-night cycles on earth throughout the four seasons. In many
      animals, including the fruit fly Drosophila melanogaster, two separate but
      mutually coupled clocks in the brain -morning (M) and evening (E) oscillators-
      control the activity in the morning and evening. M and E oscillators are thought
      to track dawn and dusk, respectively. This alters the phase-angle between the two
      oscillators under different day lengths, optimally adapting the animal's activity
      pattern to colder short and warmer long days. Using excellent genetic tools,
      Drosophila researchers have addressed the neural basis of the two oscillators and
      could partially track these to distinct clock cells in the brain. Nevertheless,
      not all data are consistent with each other and many questions remained open. So
      far, most studies about M and E oscillators focused on the influence of light
      (photoperiod). Here, we will review the effects of light and temperature on the
      two oscillators, will update the present knowledge, discuss the limitations of
      the model, and raise questions that have to be addressed in the future.

PMID- 22877660
TI  - Circadian system from conception till adulthood.
AB  - In mammals, the circadian system is composed of the central clock in the
      hypothalamic suprachiasmatic nuclei and of peripheral clocks that are located in
      other neural structures and in cells of the peripheral tissues and organs. In
      adults, the system is hierarchically organized so that the central clock provides
      the other clocks in the body with information about the time of day. This
      information is needed for the adaptation of their functions to cyclically
      changing external conditions. During ontogenesis, the system undergoes
      substantial development and its sensitivity to external signals changes.
      Perinatally, maternal cues are responsible for setting the phase of the
      developing clock, while later postnatally, the LD cycle is dominant. The central
      clock attains its functional properties during a gradual and programmed process.
      Peripheral clocks begin to exhibit rhythmicity independent of each other at
      various developmental stages. During the early developmental stages, the
      peripheral clocks are set or driven by maternal feeding, but later the central
      clock becomes fully functional and begins to entrain the periphery. During the
      perinatal period, the central and peripheral clocks seem to be vulnerable to
      disturbances in external conditions. Further studies are needed to understand the
      processes of how the circadian system develops and what degree of plasticity and
      resilience it possesses during ontogenesis. These data may lead to an assessment
      of the contribution of disturbances of the circadian system during early
      ontogenesis to the occurrence of circadian diseases in adulthood.

PMID- 22877661
TI  - When does it start ticking? Ontogenetic development of the mammalian circadian
      system.
AB  - Circadian rhythms in physiology and behavior ensure that vital functions are
      temporally synchronized with cyclic environmental changes. In mammals, the
      circadian system is conducted by a central circadian rhythm generator that
      resides in the hypothalamic suprachiasmatic nucleus (SCN) and controls multiple
      subsidiary circadian oscillators in the periphery. The molecular clockwork in SCN
      and peripheral oscillators consists of autoregulatory
      transcriptional/translational feedback loops of clock genes. The adult circadian
      system is synchronized to the astrophysical day by light whereas the fetal and
      neonatal circadian system entrains to nonphotic rhythmic maternal signals. This
      chapter reviews maturation and entrainment of the central circadian rhythm
      generator in the SCN and of peripheral oscillators during ontogenetic
      development.

PMID- 22877662
TI  - The circadian output signals from the suprachiasmatic nuclei.
AB  - The suprachiasmatic nuclei (SCN) of the anterior hypothalamus comprise a self
      sustained biological clock generating an endogenous ~24-h circadian rhythm,
      driving many overt daily rhythms in the body. An important remaining question is
      how the SCN neurons communicate with their efferent targets to control the daily
      oscillations in behavior and physiology. In this chapter, we summarize several
      signaling factors that may serve as such SCN output factors. Whereas vasopressin
      may be involved in the regulation of circadian hormone rhythms, SCN-derived
      prokineticin 2 (PK2), TGF-alpha, and cardiotrophin-like cytokine (CLC) may serve
      as output factors for other circadian rhythms, including locomotor activity, body
      temperature, and energy metabolism. The circadian rhythm in firing activity of
      SCN neurons is also likely to be a critical output signaling mechanism. The
      likely involvement of these output factors in the generation of the circadian
      rhythm in SCN neuronal firing activity is also discussed.

PMID- 22877663
TI  - Suprachiasmatic nucleus: cellular clocks and networks.
AB  - The suprachiasmatic nucleus (SCN), the master circadian clock of mammals, is
      composed of multiple circadian oscillator neurons. Most of them exhibit
      significant circadian rhythms in their clock gene expression and spontaneous
      firing when cultured in dispersed cells, as well as in an organotypic slice. The
      distribution of periods depends on the SCN tissue organization, suggesting that
      cell-to-cell interaction is important for synchronization of the constituent
      oscillator cells. This cell-to-cell interaction involves both synaptic
      interactions and humoral mediators. Cellular oscillators form at least three
      separate but mutually coupled regional pacemakers, and two of them are involved
      in the photoperiodic regulation of behavioral rhythms in mice. Coupling of
      cellular oscillators in the SCN tissue compensates for the dysfunction due to
      clock gene mutations, on the one hand, and desynchronization within and between
      the regional pacemakers that suppresses the coherent rhythm expression from the
      SCN, on the other hand. The multioscillator pacemaker structure of the SCN is
      advantageous for responding to a wide range of environmental challenges without
      losing coherent rhythm outputs.

PMID- 22877664
TI  - Dynamic neuronal network organization of the circadian clock and possible
      deterioration in disease.
AB  - In mammals, the suprachiasmatic nuclei (SCNs) function as a circadian pacemaker
      that drives 24-h rhythms in physiology and behavior. The SCN is a multicellular
      clock in which the constituent oscillators show dynamics in their functional
      organization and phase coherence. Evidence has emerged that plasticity in phase
      synchrony among SCN neurons determines (i) the amplitude of the rhythm, (ii) the
      response to continuous light, (iii) the capacity to respond to seasonal changes,
      and (iv) the phase-resetting capacity. A decrease in circadian amplitude and
      phase-resetting capacity is characteristic during aging and can be a result of
      disease processes. Whether the decrease in amplitude is caused by a loss of
      synchronization or by a loss of single-cell rhythmicity remains to be determined
      and is important for the development of strategies to ameliorate circadian
      disorders.

PMID- 22877665
TI  - Interaction of central and peripheral clocks in physiological regulation.
AB  - In mammals, circadian rhythms of physiology and behavior are regulated by a
      complex network of cellular molecular oscillators distributed throughout the
      brain and peripheral tissues. A master clock in the hypothalamic suprachiasmatic
      nuclei (SCN) synchronizes internal time with the external light-dark cycle, thus
      entraining the overall rhythmicity of the organism. Recent findings have
      challenged the dominant role of the SCN in physiological regulation and it
      becomes increasingly evident that close interaction between different central and
      peripheral clocks is necessary to maintain robust circadian rhythms of physiology
      and metabolism. In this review, we summarize recent findings regarding circadian
      organization in the SCN and in other central and peripheral tissues. We outline
      the communication pathways between different tissue clocks and, exemplified by
      the regulation of glucocorticoid release from the adrenal gland and glucose
      homeostasis in the blood, characterize the interaction between different clocks
      in the regulation of physiological processes.

PMID- 22877666
TI  - Circadian rhythms in white adipose tissue.
AB  - Adipose tissue is an important endocrine organ. It is involved in the regulation
      of energy metabolism by secreting factors (adipokines) that regulate appetite,
      food intake, glucose disposal, and energy expenditure. Many of these adipokines
      display profound day/night rhythms, and accumulating evidence links disruption of
      these rhythms to metabolic diseases such as obesity and type 2 diabetes. Here, we
      briefly present the circadian system, describe the development of white adipose
      tissue (WAT) and its depot-specific characteristics and innervation, we discuss
      energy storage in WAT and, lastly, review recent findings that link circadian
      rhythmicity to adipose tissue biology and obesity.

PMID- 22877667
TI  - Circadian modulation of sleep in rodents.
AB  - Sleep is regulated by circadian and homeostatic processes. The sleep homeostat
      keeps track of the duration of prior sleep and waking and determines the
      intensity of sleep. In mammals, the homeostatic process is reflected by the slow
      waves in the non-rapid eye movement (NREM) sleep electroencephalogram (EEG). The
      circadian process is controlled by a pacemaker located in the suprachiasmatic
      nucleus of the hypothalamus and provides the sleep homeostat with a circadian
      framework. This review summarizes the changes in sleep obtained after different
      chronobiological interventions (changes in photoperiod, light availability, and
      running wheel availability), the influence of mutations or lesions in clock genes
      on sleep, and research on the interaction between sleep homeostasis and the
      circadian clock. Research in humans shows that the period of consolidated waking
      during the day is a consequence of the interaction between an increasing
      homeostatic sleep drive and a circadian signal, which promotes waking during the
      day and sleep during the night. In the rat, it was shown that, under constant
      homeostatic sleep pressure, with similar levels of slow waves in the NREM sleep
      EEG at all time points of the circadian cycle, still a small circadian modulation
      of the duration of waking and NREM sleep episodes was observed. Under similar
      conditions, humans show a clear circadian modulation in REM sleep, whereas in the
      rat, a circadian modulation in REM sleep was not present. Therefore, in the rat,
      the sleep homeostatic modulation in phase with the circadian clock seems to
      amplify the relatively weak circadian changes in sleep induced by the circadian
      clock. Knowledge about the interaction between sleep and the circadian clock and
      the circadian modulation of sleep in other species than humans is important to
      better understand the underlying regulatory mechanisms.

PMID- 22877668
TI  - Local aspects of sleep: observations from intracerebral recordings in humans.
AB  - Human sleep is considered a global phenomenon, orchestrated by central
      specialized neuronal networks modulating the whole-brain activity. However,
      recent studies point to a local regulation of sleep. Sleep disorders, such as
      sleepwalking, suggest that electroencephalographic (EEG) features of sleep and
      wakefulness might be simultaneously present in different cerebral regions.
      Recently, intracranial EEG recording techniques, mainly applied for the
      presurgical evaluation of drug-resistant epileptic patients, have provided new
      and interesting information on the activity of different cortical and subcortical
      structures during sleep in humans. In particular, it has been observed that the
      thalamus, during the transition between wake and sleep undergoes a deactivation
      process that precedes the one occurring within the cortex, with extensive
      cortical territories maintaining an activated pattern for several minutes after
      the thalamic deactivation. Very recent intracerebral EEG studies have also shown
      that human NREM sleep can be characterized by the coexistence of wake-like and
      sleep-like EEG patterns in different cortical areas. Moreover, unit-firing
      recordings in multiple brain regions of neurosurgical patients evidenced that
      most sleep slow waves and the underlying active and inactive neuronal states do
      occur locally. These findings add a new dimension to the concept of local sleep
      regulation and opens new perspectives in the interpretation of the substrates
      underlying behavioral states of vigilance. The implications for sleep medicine
      are also discussed.

PMID- 22877669
TI  - The circadian clock component PERIOD2: from molecular to cerebral functions.
AB  - The circadian clock is based on a molecular oscillator, which simulates the
      external day within nearly all of a body's cells. This "internalized" day then
      defines activity and rest phases for the cells and the organism by generating
      precise rhythms in the metabolism, physiology, and behavior. In its perfect
      state, this timing system allows for the synchronization of an organism to its
      environment and this may optimize energy handling and responses to daily
      recurring challenges. However, nowadays, we believe that desynchronization of an
      organism due to its lifestyle or problems with its circadian clock not only
      causes discomfort but also may aggravate conditions such as depression, metabolic
      syndrome, addiction, or cancer. In this review, we focus on one simple cogwheel
      of the mammalian circadian clock, the PERIOD2 (PER2) protein. Originally
      identified as an integral part of the molecular mechanism that yields overt
      rhythms of about 24h, more recently multiple other functions have been
      identified. In essence, the PER proteins, in addition to their important function
      within the molecular oscillator, can be seen not only as integrators on the input
      side of the circadian clock but also as mediators of clock output. This diversity
      in their function is possible, because the PER proteins can interact with a
      multitude of other proteins transferring oscillator timing information to the
      latter. In this fashion, the circadian clock synchronizes many rhythmic
      processes.

PMID- 22877670
TI  - Generation of mouse mutants as tools in dissecting the molecular clock.
AB  - Elucidation of the molecular basis of mammalian circadian rhythms has progressed
      dramatically in recent years through the characterization of mouse mutants. With
      the implementation of numerous mouse genetics programs, comprehensive sets of
      mutations in genes affecting circadian output measures have been generated.
      Although incomplete, existing arrays of mutants have been instrumental in our
      understanding of how the internal SCN clock interacts with the environment and
      how it conveys its rhythm to remote oscillators. The use of ENU mutagenesis has
      proven to be a significant contributor, generating mutations leading to subtle
      and distinct alterations in circadian protein function. In parallel, progress
      with mouse gene targeting allows one to study gene function in depth by ablating
      it entirely, in specific tissues at specific times, or by targeting specific
      functional domains. This has culminated in worldwide efforts to target every gene
      in the mouse genome allowing researchers to study multiple gene targeting effects
      systematically.

PMID- 22877671
TI  - In search of a temporal niche: social interactions.
AB  - Circadian rhythms can be entrained to periodic cues in the environment including
      the solar day, food resources, and temperature. Work on a variety of organisms
      has suggested that social interactions within and between species may also
      influence circadian rhythmicity, but conceptual and technical difficulties
      relating to animal models, housing environments, rhythm assays, and experimental
      design have complicated mechanistic investigations in the laboratory. We review
      these issues and introduce the gregarious Nile grass rat, Arvicanthis niloticus,
      as a suitable model for research on this problem. Understanding social influences
      on temporal organization at this supra-organismal, community level is of
      considerable translational value, as its implications range from conservation
      biology to human health.

PMID- 22877672
TI  - In search of a temporal niche: environmental factors.
AB  - Time as an ecological niche variable or "temporal niche" can be defined in the
      context of the most prominent environmental cycles, including the tidal cycle,
      the lunar day and month, the solar day, and the earth year. For the current
      review, we focus on the 24-h domain generated through the earth's rotation around
      its axis (solar day). The daily environmental cycles of light and temperature are
      a dominant ecological factor generating a variety of adaptations among animals.
      In this review, we describe these adaptations with a special focus on the visual
      system and on the adaptive plasticity of activity patterns. Our goals are: (1)
      Underscore the importance of the 24-h time axis as critical variable in the
      ecological niche. (2) Highlight cases of temporal niche switches at the
      evolutionary timescale (phylogenetic level). (3) Review temporal niche switching
      within an individual's lifespan. (4) Evaluate possible underlying mechanisms for
      temporal niche switching. (5) Describe a new hypothesis of circadian
      thermoenergetics which may explain several cases of temporal niche switching in
      mammals. With this, we hope to inspire experiments under natural conditions or
      more complex laboratory environments, aimed to reveal environmental factors and
      mechanisms underlying specific temporal programs.

PMID- 22877673
TI  - Feedback actions of locomotor activity to the circadian clock.
AB  - The phase of the mammalian circadian system can be entrained to a range of
      environmental stimuli, or zeitgebers, including food availability and light.
      Further, locomotor activity can act as an entraining signal and represents a
      mechanism for an endogenous behavior to feedback and influence subsequent
      circadian function. This process involves a number of nuclei distributed across
      the brain stem, thalamus, and hypothalamus and ultimately alters SCN electrical
      and molecular function to induce phase shifts in the master circadian pacemaker.
      Locomotor activity feedback to the circadian system is effective across both
      nocturnal and diurnal species, including humans, and has recently been shown to
      improve circadian function in a mouse model with a weakened circadian system.
      This raises the possibility that exercise may be useful as a noninvasive
      treatment in cases of human circadian dysfunction including aging, shift work,
      transmeridian travel, and the blind.

PMID- 22877675
TI  - Nutrition and the circadian timing system.
AB  - Life on earth has evolved under the daily rhythm of light and dark. Consequently,
      most creatures experience a daily rhythm in food availability. In this review, we
      first introduce the mammalian circadian timing system, consisting of a central
      clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in various
      metabolic tissues including liver, pancreas, and intestine. We describe how
      peripheral clocks are synchronized by the SCN and metabolic signals. Second, we
      review the influence of the circadian timing system on food intake behavior,
      activity of the gastrointestinal system, and several aspects of glucose and lipid
      metabolism. Third, the circadian control of digestion and metabolism may have
      important implications for several aspects of food intake in humans. Therefore,
      we review the human literature on health aspects of meal timing, meal frequency,
      and breakfast consumption, and we describe the potential implications of the
      clock system for the timing of enteral tube feeding and parenteral nutrition.
      Finally, we explore the connection between type 2 diabetes and the circadian
      timing system. Although the past decade has provided exciting knowledge about the
      reciprocal relation between biological clocks and feeding/energy metabolism,
      future research is necessary to further elucidate this fascinating relationship
      in order to improve human health.

PMID- 22877674
TI  - The impact of the circadian timing system on cardiovascular and metabolic
      function.
AB  - Epidemiological studies show that adverse cardiovascular events peak in the
      morning (i.e., between 6 AM and noon) and that shift work is associated with
      cardiovascular disease, obesity, and diabetes. The endogenous circadian timing
      system modulates certain cardiovascular risk markers to be highest (e.g.,
      cortisol, nonlinear dynamic heart rate control, and platelet activation) or to
      respond most unfavorably to stressors such as exercise (e.g., epinephrine,
      norepinephrine, and vagal cardiac modulation) at an internal body time
      corresponding to the time of day when adverse cardiovascular events most likely
      occur. This indicates that the circadian timing system and its interaction with
      external cardiovascular stressors (e.g., physical activity) could contribute to
      the morning peak in adverse cardiovascular events. Moreover, circadian
      misalignment and simulated night work have adverse effects on cardiovascular and
      metabolic function. This suggests that misalignment between the behavioral cycle
      and the circadian timing system in shift workers contributes to that population's
      increased risk for cardiometabolic disease.

PMID- 22877677
TI  - Noisy and individual, but doable: shift-work research in humans.
AB  - Working around the clock is common for many occupations, as diverse as nurses,
      truck drivers, physicians, steel workers, and pilots. Each shift-work profession
      is individual in more aspects than just work hours and individual work scenarios,
      each posing a different impact on the health of workers. Related health problems
      in shift workers, therefore, are also diverse and encompass sleep problems,
      metabolic and cardiovascular system disturbances, as well as cancer. Little is
      known about how all these individual factors influence a shift worker's health
      status, partly because many shift-work studies show inconsistent results. In
      addition, these individual factors create many methodological difficulties for
      researchers who investigate such work scenarios. This chapter presents examples
      from our laboratory and field studies of shift workers, which emphasize the
      importance of taking individual circumstances into account. Both study
      approaches, laboratory and field based, are needed to fully account for the
      difficulties that shift-work studies pose on both workers and researchers.
      Finally, understanding the mechanisms that underpin interindividual differences
      in response to shift work will advance our understanding of how to design better
      and healthier shift-work schedules in the future.

PMID- 22877678
TI  - The evolutionary physiology of photoperiodism in vertebrates.
AB  - The capacity to measure day length (photoperiod) is a trait subject to intense
      evolutionary pressure, and the circadian system has become an important part of
      the photoperiodic machinery. With the exception of mammals, vertebrates possess
      multiple sites of photosensitivity within the central nervous system through
      which light responses may be coordinated. Of these, deep brain photoreceptors
      play a special role in photoperiodism in nonmammalian vertebrates, independent of
      either retinal or pineal pathways. In mammals, the pineal hormone, melatonin has
      assumed a function orthologous to that of deep brain photoreceptors in other
      vertebrates. Contrasting with this dichotomy in photoperiodic input pathways,
      downstream signal processing to produce switch-like seasonal responses is largely
      conserved and appears to center on photoperiodic control of thyroid hormone
      bioavailability within the hypothalamus. Recent studies implicate the clock
      controlled gene eyes absent 3 in linking the circadian clock to photoperiodic
      responses, dictating the seasonal level of expression of thyroid-stimulating
      hormone by a specialized population of photoperiodically sensitive cells in the
      pituitary stalk which in turn govern thyroid hormone metabolism in the basal
      hypothalamus. This ancestral control pathway appears to have originated prior to
      the divergence of the mammalian and avian vertebrate lineages.

PMID- 22877676
TI  - Managing neurobehavioral capability when social expediency trumps biological
      imperatives.
AB  - Sleep, which is evolutionarily conserved across species, is a biological
      imperative that cannot be ignored or replaced. However, the percentage of
      habitually sleep-restricted adults has increased in recent decades. Extended work
      hours and commutes, shift work schedules, and television viewing are particularly
      potent social factors that influence sleep duration. Chronic partial sleep
      restriction, a product of these social expediencies, leads to the accumulation of
      sleep debt over time and consequently increases sleep propensity, decreases
      alertness, and impairs critical aspects of cognitive functioning. Significant
      interindividual variability in the neurobehavioral responses to sleep restriction
      exists-this variability is stable and phenotypic-suggesting a genetic basis.
      Identifying vulnerability to sleep loss is essential as many adults cannot
      accurately judge their level of impairment in response to sleep restriction.
      Indeed, the consequences of impaired performance and the lack of insight due to
      sleep loss can be catastrophic. In order to cope with the effects of social
      expediencies on biological imperatives, identification of biological (including
      genetic) and behavioral markers of sleep loss vulnerability as well as
      development of technological approaches for fatigue management are critical.

PMID- 22877679
TI  - A kiss for daily and seasonal reproduction.
AB  - Reproduction is a fundamental biological function ensuring individual descendant
      survival and species perpetuity. It is an energy-consuming process, and
      therefore, all underlying mechanisms have to work in synchrony to ensure
      reproductive success. Synchronization of reproductive activity with the best time
      of the day or the year is part of such adaptive processes. Recently, a
      neuropeptide named kisspeptin, synthesized in two discrete hypothalamic nuclei,
      the anteroventral periventricular nucleus and the arcuate nucleus, has been
      demonstrated to be a potent stimulator operating upstream of the gonadotropic
      axis. In this review, we show how kisspeptinergic neurons integrate daily and
      seasonal time cues to synchronize reproductive activity with the cycling
      environment.

PMID- 22877680
TI  - Circannual rhythm in the varied carpet beetle, Anthrenus verbasci.
AB  - Although circannual rhythms controlling different physiological processes and
      various aspects of behavior have been reported in numerous organisms, our
      understanding of the underlying biological mechanisms is still quite limited. We
      examined the mechanisms controlling the circannual pupation rhythm of the varied
      carpet beetle, Anthrenus verbasci. This rhythm is self-sustainable, exhibits
      temperature compensation of the periodicity, and is entrainable to environmental
      changes. In addition, the circannual phase response curves to a photoperiod pulse
      display Type 0 or Type 1 resetting, depending on the duration of the pulse. Thus,
      we infer that this rhythm is derived from a self-sustaining biological oscillator
      with a period of about a year, that is, a circannual clock, analogous to the
      circadian clock. Further, a circadian clock appears to mediate photoperiodic time
      measurement for phase resetting of the circannual clock. Based on these results
      and previous research performed in other organisms, we discuss the general
      characteristics of the physiological mechanisms underpinning circannual
      rhythmicity.

PMID- 22877681
TI  - Avian migration: temporal multitasking and a case study of melatonin cycles in
      waders.
AB  - Timing "in the real world" must cope with the temporal complexity of natural
      environments. Extreme examples for the resultant "multitasking" are migratory
      birds, which precisely time movements to remote areas. New field technologies
      highlight temporal accuracy, while captivity studies emphasize underlying
      programs and plasticity of schedules. After reviewing these findings, we focus on
      waders, which undertake spectacular long-distance migrations, have robust
      circannual clocks, and cope with diel, tidal, and polar environments. To explore
      features that may facilitate such multitasking, we speculated that melatonin
      amplitudes are low and damped during seasons when entrainment to subtle
      Zeitgebers occurs. We measured melatonin profiles under European daylength in two
      species with different ecologies and found low-amplitude melatonin cycles that
      changed over the year. Annual patterns neither fully supported our hypothesis,
      nor simply reflected daylight availability. While migratory birds are inspiring
      models for chronobiology, mechanistic understanding of their multitasking is
      still poor.

PMID- 22877682
TI  - Neurobiology of Circadian Timing. Preface.

PMID- 22877683
TI  - Vertebrobasilar dolichoectasia causing a presentation resembling basilar-type
      migraine.

PMID- 22877684
TI  - Clinical analysis of factors predisposing the recurrence of primary intracerebral
      hemorrhage in patients taking anti-hypertensive drugs: a prospective cohort
      study.
AB  - OBJECTIVE: The study examined differences in the recurrence rate of primary
      intracerebral hemorrhage (P-ICH) according to anti-hypertensive drug (AHD) use by
      patients with hypertension. METHODS: This prospective, longitudinal cohort study
      was performed on 2384 patients diagnosed with supratentorial P-ICH and
      hypertension in the stroke unit of a single-center. During follow-up (mean,
      44.9+/-31.5 months), investigators interviewed subjects or caregivers by
      telephone or examined patients every 3-6 months. Target blood pressure was
      <140/90 mmHg in the P-ICH cohort with hypertension. RESULTS: Of 1317 P-ICH
      patients defined to be taking AHDs, P-ICH recurrence occurred in 129 (9.8%). 1211
      patients (92.0%) reached target blood pressure. In multivariate regression
      analysis, advanced age (>=70 years), poor functional outcome after first P-ICH,
      lobar location of P-ICH, previous history of cerebral ischemia, diuretic
      monotherapy and alpha- or beta-blocker monotherapy were associated with risk of
      recurrence. CONCLUSIONS: Although hypertension is the most important factor for
      preventing P-ICH recurrence, we found that, even in the presence of optimal anti
      hypertensive medication, recurrent P-ICH attack can occur. Therefore, management
      of other risk factors of recurrent P-ICH, such as modification of lifestyle, must
      be considered in treating the P-ICH patients.

PMID- 22877685
TI  - Novel method for screening Saccharomyces cerevisiae mutants with increased sulfur
      containing compounds: color-based selection of ade1 or ade2 mutants.
AB  - We identified Saccharomyces cerevisiae mutants with 100% higher intracellular
      glutathione using 1-methyl-3-nitro-1-nitrosoguanidine mutagenesis. This method
      employs visual selection of the most pigmented colonies among met30 strains
      carrying ade1 and ade2 mutations. Since the method does not involve genetic
      engineering, the mutants are suitable for use in the food industry.

PMID- 22877686
TI  - Yeast ecology of vineyards within Marsala wine area (western Sicily) in two
      consecutive vintages and selection of autochthonous Saccharomyces cerevisiae
      strains.
AB  - In this work, the yeast ecology associated with the spontaneous fermentation of
      Grillo cultivar grapes from 10 vineyards was analyzed from grape harvest till
      complete consumption of must sugars. The microbiological investigation started
      with the plate count onto two culture media to distinguish total yeasts (TY) and
      presumptive Saccharomyces (PS). Yeasts were randomly isolated and identified by a
      combined genotypic approach consisting of restriction fragment length
      polymorphism (RFLP) of 5.8S rRNA gene and 26S rRNA and sequencing of D1/D2 domain
      of the 26S rRNA gene, which resulted in the recognition of 14 species belonging
      to 10 genera. The distribution of the yeasts within the vineyards showed some
      differences in species composition and concentration levels among 2008 and 2009
      vintages. Due to the enological relevance, all Saccharomyces cerevisiae isolates
      were differentiated applying two genotypic tools (interdelta analysis and
      microsatellite multiplex PCR of polymorphic microsatellite loci) that recognized
      51 strains. Based on the low production of H(2)S, acetic acid and foam, ethanol
      resistance, growth in presence of high concentrations of potassium metabisulphite
      (KMBS) and CuSO(4) and at low temperatures, 14 strains were selected and used as
      starter to ferment grape must at 13  degrees C and 17  degrees C in presence of
      100 mg/L of KMBS. Three strains (CS160, CS165 and CS182) showed optimal
      technological aptitudes.

PMID- 22877687
TI  - Measurement of aldehyde dehydrogenase 1 expression defines a group with better
      prognosis in patients with non-small cell lung cancer.
AB  - Aldehyde dehydrogenase 1 (ALDH1) has been suggested as a surrogate biomarker for
      cancer stem cells in breast cancer and other tumors. We quantitatively measured
      ALDH1 in two large cohorts of patients with non-small cell lung cancer (NSCLC)
      and investigated its prognostic value. The AQUA method of quantitative
      immunofluorescence was used to measure ALDH1 in 134 patients with NSCLC from Yale
      University and 296 patients with NSCLC from Sotiria and Patras University
      hospitals in Greece, using tissue microarrays. Patients were classified as
      positive or negative for ALDH1 based on the detection threshold for quantitative
      immunofluorescence. Patients with squamous cell carcinoma had higher scores than
      patients with adenocarcinoma. Detectable ALDH1 predicted better prognosis in both
      cohorts (P = 0.0035 for the Yale cohort; P = 0.0238 for the Sotiria/Patras
      cohorts). The effect of ALDH1 expression was independent of clinicopathologic
      factors in the Yale cohort (risk ratio = 3.2, P = 0.0008), but did not reach
      significance in the Sotiria/Patras cohort (hazard ratio = 1.51, P = 0.08). Among
      patients with adenocarcinoma, the ALDH1-negative group had shorter survival
      compared with the ALDH1-positive group in the Yale cohort (P = 0.00001), but not
      in the Sotiria/Patras cohort (P = 0.45). Unlike breast cancer, in which ALDH1
      expression predicts poor outcome, in NSCLC our exploratory and retrospective
      study indicates that ALDH1 expression is associated with favorable outcome.

PMID- 22877688
TI  - Women and dementia--not forgotten.
AB  - OBJECTIVES: To inform our understanding of gender, sex and dementia for women's
      health and highlight both current and emerging issues. The purpose of this
      article is to provide policy makers with an improved understanding of the sex
      specific and gender dimensions that exist to help formulate more effective and
      targeted health and social care policies. METHODS: The findings, from which this
      article is formed, were reported in the form of an evidence review which included
      both qualitative and quantitative studies from academic, clinical, research and
      grey literature. The issue of dementia was approached through the prism of sex
      and gender, in an attempt to understand the complex interaction between
      biologically and socially constructed roles. FINDINGS: There continues to be a
      pressing need to raise awareness of the impact of discrimination, exclusion and
      stigma associated with dementia and the impact for women in particular. While the
      'feminisation of ageing' is a widely recognised trend, hitherto a comprehensive
      approach to the impact of dementia on women remains largely unexplored with
      regards to research and policy impact. Women face a 'triple jeopardy' as a result
      of the associated stigma attached to their age, gender and decline in cognitive
      functions. The need for further research of the sex and gender specific risk
      factors for dementia is highlighted alongside the need for greater evidence on
      diagnosis, treatment and response. The findings also expose the gender specific
      nature of unpaid care and the associated consequences for women as a result.
      CONCLUSIONS: Based on analysis of the available data and assisted by the gender
      lens tool, the findings presented in this article posit that women across many
      parts of the world are and will continue to disproportionately bear the burden of
      dementia, with particular regard to either living with dementia and/or caring for
      family members with dementia.

PMID- 22877689
TI  - Experimental infection of suckling mice by subcutaneous inoculation with
      Oropouche virus.
AB  - Oropouche virus, of the family Bunyaviridae, genus Orthobunyavirus, serogroup
      Simbu, is an important causative agent of arboviral febrile illness in Brazil. An
      estimated 500,000 cases of Oropouche fever have occurred in Brazil in the last 30
      years, with recorded cases also in Panama, Peru, Suriname and Trinidad. We have
      developed an experimental model of Oropouche virus infection in neonatal BALB/c
      mouse by subcutaneous inoculation. The vast majority of infected animals
      developed disease on the 5th day post infection, characterized mainly by lethargy
      and paralysis, progressing to death within 10 days. Viral replication was
      documented in brain cells by in situ hybridization, immunohistochemistry and
      virus titration. Multi-step immunohistochemistry indicated neurons as the main
      target cells of OROV infection. Histopathology revealed glial reaction and
      astrocyte activation in the brain and spinal cord, with neuronal apoptosis.
      Spleen hyperplasia and mild meningitis were also found, without viable virus
      detected in liver and spleen. This is the first report of an experimental mouse
      model of OROV infection, with severe involvement of the central nervous system,
      and should become useful in pathogenesis studies, as well as in preclinical
      testing of therapeutic interventions for this emerging pathogen.

PMID- 22877690
TI  - Efficacy of cilostazol in preventing aspiration pneumonia in acute cerebral
      infarction.
AB  - This retrospective study examined the effectiveness of cilostazol in preventing
      aspiration pneumonia in patients with acute cerebral infarction. The 189 subjects
      ranged in age from 31 to 95 years and included 57 with small-artery occlusion,
      107 with large-artery atherothrombosis, and 25 with other disorders. Patients
      with cardiogenic cerebral embolism or preexisting pneumonia at the time of
      hospital admission were excluded from the analysis. Neurologic symptoms,
      cognitive function, and swallowing function were assessed at the first clinical
      examination, and the ability to perform activities of daily living was assessed
      at both hospital admission and discharge. Outcome and food intake status were
      also assessed at hospital discharge. Pneumonia was detected in 27 of 189 subjects
      (14.3%), in 20 subjects during nasogastric tube feeding implemented because of
      oral intake difficulties (fasting group) and in 7 subjects after initiation of
      oral feeding (oral intake group). Cilostazol was administered to 48 of the 189
      subjects (25.4%). The incidence of pneumonia was 6.3% (3 of 48) in patients who
      received cilostazol, compared with 17% (24 of 141) in those who did not receive
      cilostazol. Our data suggest that cilostazol appears to prevent the occurrence of
      pneumonia in both the chronic and acute stages of cerebral infarction. 

PMID- 22877691
TI  - Poor health-related quality of life is associated with long-term mortality in
      young adults with cerebral infarction.
AB  - BACKGROUND: Our aim was to investigate the effect of health-related quality of
      life (HRQOL) on subsequent mortality in young ischemic stroke patients in a
      population-based study. METHODS: Young ischemic stroke patients were invited to a
      follow-up on average 6 years after their index stroke. HRQOL was measured by
      Short-Form 36 (SF-36) and the Nottingham Health Profile (NPH). Data on
      socioeconomic and functional states were obtained. Subsequent survival was
      obtained by examining the official population registry. Multivariate analyses
      were performed. RESULTS: One hundred eighty-eight patients were included. The
      mean age on follow-up was 48 years, and the subsequent follow-up period was 12
      years. Cox regression analysis revealed that mortality was associated with NHP
      sum score (P < .001) after adjusting for age (P = .09), sex (P = .11), and
      alcoholism (P = .04). Cox regression analyses, including subscores of SF-36 or
      NHP separately, revealed that mortality was associated with pain (P = .05), sleep
      disturbances (P = .02), and physical function (P = .02) after adjusting for
      confounders. CONCLUSIONS: Poor HRQOL is associated with subsequent long-term
      mortality in young adults with ischemic stroke and this may pertain particularly
      to pain, sleep disturbances and low physical fitness.

PMID- 22877692
TI  - Amusia for pitch caused by right middle cerebral artery infarct.
AB  - A 61-year-old right-handed man with hypertension and dyslipidemia noted that he
      was singing along to classic rock songs on his car radio, but his voice was off
      pitch. Six days later, a magnetic resonance imaging scan of his brain revealed a
      cerebral infarct of the right temporal parietal cortex and insula. Case reports
      of the precise anatomic correlates of disordered pitch musical processing have
      been few and fragmentary. The anatomic involvement of our case coincides with the
      areas of involvement in 3 previously reported cases. Increased awareness of
      amusia as a rare clinical presentation of stroke should lead to earlier stroke
      intervention. 

PMID- 22877693
TI  - Disaster preparedness in an Australian urban trauma center: staff knowledge and
      perceptions.
AB  - INTRODUCTION: A substantial barrier to improving disaster preparedness in
      Australia is a lack of prescriptive national guidelines based on individual
      hospital capabilities. A recent literature review revealed that only one
      Australian hospital has published data regarding its current preparedness level.
      OBJECTIVES: To establish baseline levels of disaster knowledge, preparedness, and
      willingness to respond to a disaster among one hospital's staff, and thus enable
      the implementation of national disaster preparedness guidelines based on
      realistic capabilities of individual hospitals. METHODS: An anonymous
      questionnaire was distributed to individuals and departments that play key roles
      in the hospital's external disaster response. Questions concerned prior education
      and experience specific to disasters, general preparedness knowledge, perceived
      preparedness of themselves and their department, and willingness to respond to a
      disaster from a conventional and/or chemical, biological, or radiological
      incident. RESULTS: Responses were received from 140 individuals representing nine
      hospital departments. Eighty-three participants (59.3%) had previously received
      disaster education; 53 (37.9%) had attended a disaster simulation drill, and 18
      (12.9%) had responded to an actual disaster. The average disaster preparedness
      knowledge score was 3.57 out of 10. The majority of respondents rated themselves
      as "not really" prepared and were "unsure" of their respective departments' level
      of preparedness. Most respondents indicated a willingness to participate in both
      a conventional incident involving burns and/or physical trauma, and an incident
      involving chemical, biological or radiological (CBR) weapons. CONCLUSIONS:
      Australian hospital staff are under-prepared to respond to a disaster because of
      a lack of education, insufficient simulation exercises, and limited disaster
      experience. The absence of specific national standards and guidelines through
      which individual hospitals can develop their capabilities further compounds the
      poverty in preparedness.

PMID- 22877694
TI  - Vibrational spectroscopic analysis of some Hofmann-Td type complexes.
AB  - New Hofmann-T(d) type complexes in the form of Ni(4Chpy)(2)M(CN)(4) (M=Cd or Hg
      and 4chpy=4-(3-cyclohexen-1-yl)pyridine) have been prepared and their FT-IR and
      FT-Raman spectra have been reported. The results suggest that present compounds
      are similar in structure to the Hofmann-T(d) type complexes, in which the M atom
      is tetrahedrally coordinated to the carbon atoms of the four cyanide groups,
      while the Ni atom is octahedrally surrounded by six nitrogen atoms, two of which
      are from 4chpy ligands which have been coordinated as a unidentate ligand and the
      rest are from cyanide groups. In this host structure, the M(CN)(4) groups have
      been linked by the Ni(4chpy)(2) moieties to form a three-dimensional network.

PMID- 22877695
TI  - Expression pattern of Galectin 4 in rat placentation.
AB  - Galectin 4 (Gal4) is abundantly expressed in the epithelium of the
      gastrointestinal tract, and functional analysis has concentrated on its roles
      associated with polarized membrane trafficking. This study aimed to investigate
      the expression of Gal4 in placentation. The expression level of Gal4 was revealed
      to be lower in differentiated Rcho-1 cells (a model system of rat trophoblast
      differentiation) than in proliferative cells. In the rat placenta,
      immunohistochemical analysis showed that Gal4 is preferentially located in the
      maternal-fetal junctional zone. These results suggest that down-regulation of
      Gal4 may be involved in the promotion of trophoblast cell differentiation.

PMID- 22877696
TI  - Mechanism of freeze-drying drug nanosuspensions.
AB  - Drug nanoparticles prepared in a liquid medium are commonly freeze-dried for the
      preparation of an oral dosage in solid dosage form. The freezing rate is known to
      be a critical parameter for redispersible nanoformulations. However, there has
      been controversy as to whether a fast or slow freezing rate prevents irreversible
      aggregation. A systematic investigation is presented herein regarding the effect
      of both the molecular weight of the cryoprotectant and the freezing rate in order
      to elucidate the mechanism underlying irreversible aggregation. It was found that
      irreversible aggregation occurred during drying rather than freezing, although a
      proper freezing rate is critical. A more homogeneous distribution of the
      cryoprotectant and drug nanoparticles led to more redispersible powders. Thus,
      keeping the local concentration distribution of the nanoparticles and
      cryoprotectant fixed during the freezing step plays a critical role in how the
      freezing rate affects the redispersibility. The kinetic approach of excluding the
      tendency of ice crystal growth permitted an explanation of the controversial
      results. This study will facilitate an in-depth understanding of the aggregation
      process of nanoparticles or proteins during freeze-drying.

PMID- 22877697
TI  - Intranasal delivery of HMGB1-binding heptamer peptide confers a robust
      neuroprotection in the postischemic brain.
AB  - High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In a
      previous report, we showed that HMGB1 is massively released during NMDA-induced
      acute damaging process in the postischemic brain and triggers inflammatory
      processes and induces neuronal apoptosis. We have also reported a robust
      neuroprotection of intranasally delivered HMGB1 siRNA in the postischemic rat
      brain (middle cerebral artery occlusion (MCAO), 60 min). In the present study, we
      investigated the therapeutic efficacy of intranasally delivered HMGB1 binding
      heptamer peptide (HBHP; HMSKPVQ), which was selected using a phage display
      approach, in the same stroke animal model. A pull-down assay using biotin-labeled
      HBHP showed that HBHP binds directly to HMGB1, specifically to HMGB1 A box,
      confirming HMGB1/HBHP interaction. HBHP significantly suppressed HMGB1-mediated
      neuronal cell death in primary cortical cultures and HMGB1/HBHP binding was
      detected in NMDA-conditioned culture media. However, a heptamer peptide composed
      of a scrambled sequence of the seven amino acids in HBHP failed to bind HMGB1 and
      had no protective effect. Furthermore, HBHP (300 ng) delivered intranasally at 30
      min before MCAO significantly suppressed infarct volume in the postischemic rat
      brain (maximal reduction by 41.8+/-5.4%) and ameliorated neurological and
      behavioral deficits. In contrast, scrambled heptamer peptide had no protective
      effect at the same dose. Together these results suggest that intranasal HBHP
      ameliorates neuronal damage in the ischemic brain by binding HMGB1, which might
      inhibit the function of HMGB1 as an endogenous danger signal molecule.

PMID- 22877700
TI  - Effect of canopy shape on physical load when holding an umbrella.
AB  - The aim of the current study was to investigate the effect of the canopy shape of
      an umbrella on physical load when holding the umbrella in different
      circumstances. For this purpose, thirteen subjects participated in this study and
      muscle activity of seven muscles of the upper limb (including the forearm) was
      measured for 5 wind speeds (4, 5, 6, 7, 8 Bft) and two wind directions (front and
      side). From the results, it was seen that for the p50 value of the muscle
      activity, the umbrella with the asymmetric canopy required 62% and for the p90
      value of the muscle activity 74% of the muscle activity, on average, over all
      wind speeds - compared to the traditional umbrella. Based on these results, we
      can conclude that the physical load of holding the traditional umbrella is
      significantly higher than holding the umbrella with the asymmetric canopy shape
      in windy conditions.

PMID- 22877698
TI  - In vivo comparison of harmine efficacy against psychostimulants: preferential
      inhibition of the cocaine response through a glutamatergic mechanism.
AB  - Harmine is a beta-carboline compound that targets glutamatergic, monoaminergic,
      and GABAergic pathways underlying drug addiction. We compared the efficacy of
      harmine against different psychoactive drugs using an invertebrate (planarian)
      assay designed to quantify 'C-shape' responses. Harmine itself (0.01-10 MUM) did
      not produce C-shapes. However, when applied over the same concentration range,
      harmine significantly inhibited C-shapes elicited by cocaine, with a
      concentration of 0.1 MUM producing almost 90% inhibition. Consistent with its
      putative actions, harmine produced a similar, though less efficacious, inhibition
      of C-shapes elicited by the substituted amphetamines methamphetamine and
      mephedrone (4-methylmethcathinone) but was much less effective against nicotine.
      When tested in the presence of the glutamate transporter inhibitor dihydrokainate
      (DHK) (0.1, 1 MUM), harmine (0.1 MUM) efficacy against cocaine-induced C-shapes
      was significantly reduced. Harmine also attenuated C-shapes elicited by N-methyl
      d-aspartate (NMDA) and by glutamate itself. The present data suggest that harmine
      displays preferential efficacy against different addictive substances
      (cocaine>amphetamines>nicotine) and, at least for cocaine, is dependent on the
      glutamate system.

PMID- 22877701
TI  - Exposure to audible and infrasonic noise by modern agricultural tractors
      operators.
AB  - The wheeled agricultural tractor is one of the most prominent sources of noise in
      agriculture. This paper presents the assessment of the operator's exposure to
      audible and infrasonic noise in 32 selected modern wheeled agricultural tractors
      designed and produced by world-renowned companies in normal working conditions.
      The tractors have been in use for no longer than 4 years, with rated power of 51
      kW to up to 228 kW (as per 97/68 EC). Audible and infrasonic noise level
      measurements and occupational exposure analysis to noise were performed according
      to ISO 9612:2009 (strategy 1 - task-based measurements). The measurements were
      made in different typical work conditions inside and outside of tractors cabs.
      The results indicated that exposure levels to noise perceived by the operators
      (L(ex,Te) between 62,3 and 84,7 dB-A) and can make a small risk of potential
      adversely effects on hearing during tasks performed inside the closed cab. It
      should be remarked that uncertainty interval is wider and in in some conditions
      can occur transgression of audible noise occupational exposure limits. The
      measured audible noise levels can potentially develop the non-auditory effects.
      Analysed tractors emit considerable infrasonic noise levels that tend to exceed
      the occupational exposure limits (both inside and outside the driver's cab). The
      levels of infrasound: 83,8-111,4 dB-G. All tractors introduced for sale should be
      subjected to tests in terms of infrasonic noise levels. The applicable standards
      for low frequency noise and its measurement methods for vehicles, including
      agricultural tractors, should be scientifically revised. In the last years there
      has been a noticeable technical progress in reduction of audible noise exposure
      at the tractors operators workplaces with simultaneously lack of important works
      for limitation of exposure to infrasound. Author discuss possible health and
      ergonomic consequencies of such exposure.

PMID- 22877702
TI  - Analysing factors related to slipping, stumbling, and falling accidents at work:
      Application of data mining methods to Finnish occupational accidents and diseases
      statistics database.
AB  - The utilisation of data mining methods has become common in many fields. In
      occupational accident analysis, however, these methods are still rarely
      exploited. This study applies methods of data mining (decision tree and
      association rules) to the Finnish national occupational accidents and diseases
      statistics database to analyse factors related to slipping, stumbling, and
      falling (SSF) accidents at work from 2006 to 2007. SSF accidents at work
      constitute a large proportion (22%) of all accidents at work in Finland. In
      addition, they are more likely to result in longer periods of incapacity for work
      than other workplace accidents. The most important factor influencing whether or
      not an accident at work is related to SSF is the specific physical activity of
      movement. In addition, the risk of SSF accidents at work seems to depend on the
      occupation and the age of the worker. The results were in line with previous
      research. Hence the application of data mining methods was considered successful.
      The results did not reveal anything unexpected though. Nevertheless, because of
      the capability to illustrate a large dataset and relationships between variables
      easily, data mining methods were seen as a useful supplementary method in
      analysing occupational accident data.

PMID- 22877703
TI  - The effects of self-awareness on body movement indicators of the intention to
      deceive.
AB  - A study was conducted to investigate the body movements of participants waiting
      to be interviewed in one of two conditions: preparing to answer questions
      truthfully or preparing to lie. The effects of increased self-awareness were also
      investigated, with half of the participants facing a mirror; the other half
      facing a blank wall. Analysis of covertly obtained video footage showed a
      significant interaction for the duration of hand/arm movements between deception
      level and self-awareness. Without a mirror, participants expecting to lie spent
      less time moving their hands than those expecting to tell the truth; the opposite
      was seen in the presence of a mirror. Participants expecting to lie also had
      higher levels of anxiety and thought that they were left waiting for less time
      than those expecting to tell the truth. These findings led to the identification
      of further research areas with the potential to support deception detection in
      security applications.

PMID- 22877704
TI  - Membrane interactions of ionic liquids: possible determinants for biological
      activity and toxicity.
AB  - Ionic liquids (ILs) are a class of diverse organic salts with relatively low
      melting points (below 100 degrees C) which have attracted considerable interest
      as a promising "green" substitute for organic solvents. The broad solvation
      properties of ILs and their high solubility in water, however, present health
      risks, in particular since it was shown that many ILs exhibit cytotoxic
      properties. In this context, interactions of ILs with the cellular membrane are
      believed to constitute a primary culprit for toxicity. We present a comprehensive
      biophysical and microscopy study of membrane interactions of a series of ILs
      having different side-chain compositions and lengths, and cationic head-group
      structures and orientations. The experimental data reveal that the ILs studied
      exhibit distinct mechanisms of membrane binding, insertion, and disruption which
      could be correlated with their biological activities. The results indicate, in
      particular, that both the side chain composition and particularly the head-groups
      of ILs constitute determinants for membrane activity and consequent cell
      toxicity. This work suggests that tuning membrane interactions of ILs should be
      an important factor for designing future compounds with benign environmental
      impact.

PMID- 22877705
TI  - Binding and reorientation of melittin in a POPC bilayer: computer simulations.
AB  - We performed, using an all-atom force field, molecular dynamics computer
      simulations to study the binding of melittin to the POPC bilayer and its
      subsequent reorientation in this bilayer. The binding process involves a
      simultaneous folding and adsorption of the peptide to the bilayer, followed by
      the creation of a "U shaped" conformation. The reorientation of melittin from the
      parallel to the perpendicular conformation requires charged residues to cross the
      hydrophobic core of the bilayer. This is accomplished by a creation of defects in
      the bilayer that are filled out with water. The defects are caused by peptide
      charged residues dragging the lipid headgroup atoms along with them, as they
      reorient. With increased concentration of melittin water defects form stable
      pores; this makes it easier for the peptide N-terminus to reorient. Our results
      complement experimental and computational observations of the melittin/lipid
      bilayer interaction.

PMID- 22877706
TI  - Total glossectomy with preservation of the larynx: oncological and functional
      results.
AB  - Our aim was to analyse the overall and disease-free survival (DFS), time to
      recovery of oral feeding, and morbidity, in a consecutive series of patients who
      had total glossectomy with preservation of the larynx for advanced cancer of the
      tongue at the European institute of Oncology (Milan). From June 2002 to April
      2011, 37 patients who were treated for advanced cancer of the tongue had total
      glossectomy, bilateral neck dissection, and preservation of the larynx. Various
      flaps were used for reconstruction. Overall and disease-free survival were
      assessed from the day of operation to the latest outpatient examination.
      Postoperative morbidity and rehabilitation of feeding were also assessed. Six
      patients had major complications, four of whom had a second operation for
      necrosis of the flap. Actuarial five-year overall survival (OS) and disease-free
      survival were 54% and 47%. Twenty-four patients (65%) were operated on as their
      first treatment, and had 79% five-year overall survival and 61% 5-year disease
      free survival. Twenty-six patients were eventually able to feed orally
      postoperatively. Although this retrospective study include a limited number of
      patients, the results support the validity of total glossectomy as a safe
      procedure for advanced cancer of the tongue. Pretreated patient were previously
      treated with surgery, radiotherapy or chemoradiotherapy with curative purposes.
      Nevertheless, the long period required for recovery of oral feeding indicates
      that total glossectomy should be reserved for highly motivated patients.

PMID- 22877707
TI  - Making sense of urodynamic studies for women with urinary incontinence and pelvic
      organ prolapse: a urogynecology perspective.
AB  - The support for routine urodynamic testing in the management of women with
      urinary incontinence or pelvic organ prolapse is eroding. The reasons for this
      change largely reflect the growing evidence that urodynamic testing in this
      context renders little additional information over basic office assessment. The
      clinical features of urodynamic testing and its diagnostic and prognostic
      precision and accuracy are all problematic. As our understanding of female lower
      urinary tract dysfunction improves, the inadequacy of urodynamic testing to
      meaningfully improve patient and clinician decision making has become more
      apparent.

PMID- 22877708
TI  - Urodynamics: role in incontinence and prolapse: a urology perspective.
AB  - Changes in pelvic floor as well as urethral anatomy and function occur with
      aging, which can result in prolapse and urinary incontinence. Aside from the
      socially debilitating impact incontinence has on patient's lives, it
      significantly affects the health care systems economically. Rates of incontinence
      and pelvic organ prolapse (POP) in women of this age demographic is estimated to
      be 30% to 94%, and 1 in 8 women may require surgical repair for POP or
      incontinence by their eighth decade, with a reoperation rate of 30%. This article
      reviews the role of UDS in the evaluation of urinary incontinence and POP.

PMID- 22877709
TI  - Bulking agents: a urogynecology perspective.
AB  - A bulking agent is a material injected into the wall of the urethra to improve
      urethral coaptation in women suffering from stress incontinence. The concept was
      initially described in the 1930s when sodium morrhuate and paraffin were used to
      augment urethral resistance. Sclerosing agents were also used for inducing
      permanent urethral scaring to improve urinary leakage. Eventually, collagen and
      autologous fat were found to be efficacious, and only collagen demonstrated
      proven safety and endured extensive testing, becoming the gold standard for
      injectable agents. Since then, multiple other products have been developed by the
      industry, each with its particular success rates and complications.

PMID- 22877710
TI  - Urethral bulking: a urology perspective.
AB  - Urethral bulking therapy (UBT) is a minimally invasive procedure for stress
      urinary incontinence that is beneficial for properly selected patients. Many
      different materials are available for UBT, although none fulfill all the
      qualities of an ideal agent. In general, short-term clinical results are
      encouraging; however, over longer follow-up, results are disappointing and
      retreatment is often necessary. Proper patient selection and management of
      patient expectations are paramount to successful application of UBT.

PMID- 22877711
TI  - Midurethral slings for stress urinary incontinence: a urogynecology perspective.
AB  - Stress urinary incontinence (SUI), the involuntary leakage of urine associated
      with an increase in intraabdominal pressure (coughing, laughing, and sneezing),
      affects 12.8% to 46.0% of women. SUI is the most common type of urinary
      incontinence in women younger than 60 years and accounts for at least half of
      incontinence in all women. Retropubic and transobturator midurethral sling
      procedures are safe and effective treatments for stress urinary incontinence but
      have different complication profiles. History, examination, and additional
      testing may assist in choosing the correct sling type. Appropriate counseling and
      managing patient expectation are necessary to optimize patient satisfaction.

PMID- 22877712
TI  - Midurethral slings for all stress incontinence: a urology perspective.
AB  - The midurethral sling (MUS) is now the most commonly performed surgical treatment
      for stress urinary incontinence (SUI), and is considered the gold standard for
      patients with genuine SUI. This article examines the use of the MUS to treat all
      forms of SUI, with an emphasis on the nonindex patient (ie, intrinsic sphincter
      deficiency, lack of urethral hypermobility, mixed incontinence, failed MUS,
      concomitant prolapse, obesity, and elderly). The efficacy and safety of the MUS
      to treat SUI is assessed in these specific populations. Based on the available
      evidence, the discussion attempts to identify populations in whom MUS may not be
      appropriate.

PMID- 22877713
TI  - Role of autologous bladder-neck slings: a urogynecology perspective.
AB  - The concept of the autologous pubovaginal sling involves supporting the proximal
      urethra and bladder neck with a piece of graft material, achieving continence
      either by providing a direct compressive force on the urethra/bladder outlet or
      by reestablishing a reinforcing platform or hammock against which the urethra is
      compressed during transmission of increased abdominal pressure. Pubovaginal
      slings using a biological sling material (whether autologous, allograft, or
      xenograft) can be used successfully to manage primary or recurrent stress
      incontinence. This article addresses the indications for the use of an autologous
      bladder-neck sling, describes the surgical techniques, and discusses outcomes and
      technical considerations.

PMID- 22877714
TI  - Contemporary role of autologous fascial bladder neck slings: a urology
      perspective.
AB  - Fascial slings remain a successful and durable option for treatment of female
      stress urinary incontinence (SUI). With limited risk of disease transmission,
      extrusion, or complications associated with mesh, use of autologous fascia is an
      attractive option, particularly for complex reconstructive cases. With generally
      robust outcomes, pubovaginal slings also continue to be a viable option for
      treatment of primary SUI after appropriate patient counseling regarding risks of
      bladder outlet obstruction and de novo urgency symptoms.

PMID- 22877715
TI  - Vaginal prolapse repair: suture repair versus mesh augmentation: a urogynecology
      perspective.
AB  - Based on the growing evidence within our literature, mesh is clearly needed for
      long-term success for the repair of anterior/apical defects. Clear credentialing
      and clinical privilege criteria policies are long overdue. Current data are
      rapidly growing, with level I studies completed that demonstrate that when
      transvaginal mesh-augmented repair is used in appropriately selected patients for
      the repair of pelvic organ prolapse, the procedure has a favorable risk/benefit
      ratio when compared with suture repair. This article highlights the evolving
      clinical-based experiences of the authors that are primarily grounded in reality
      based medicine with the consideration and incorporation of evidence-based
      medicine.

PMID- 22877716
TI  - Vaginal prolapse repair: suture repair versus mesh augmentation: a urology
      perspective.
AB  - The ideal procedure for pelvic organ prolapse (POP) repair would be associated
      with a low chance of long-term anatomic recurrence in the corrected compartment
      and should not predispose the patient to de novo stress urinary incontinence
      (SUI) or POP in other compartments. The procedure should also improve the woman's
      quality of life and subjective symptoms of pelvic floor dysfunction, it should be
      safe, and not be associated with significant immediate and long-term morbidity.
      Each procedure for POP repair has strong advantages and potential detractors.
      This article discusses anterior and posterior compartment POP repairs.

PMID- 22877717
TI  - Robotic/laparoscopic prolapse repair: role of hysteropexy: a urogynecology
      perspective.
AB  - This article addresses uterine preservation at the time of pelvic floor repair.
      Currently available data on the effectiveness of pelvic organ prolapse repairs is
      based on studies in which women underwent hysterectomy at the time of pelvic
      floor repair, and cannot be extrapolated to hysteropexy. Several case series
      outline the feasibility and effectiveness of suture and mesh-augmented
      hysteropexy. Even fewer data are available regarding pregnancy risks and outcomes
      following hysteropexy. Leaving the uterus in situ at the time of pelvic floor
      repair also raises unique issues, such as the risk and management of future
      cervical or uterine abnormalities.

PMID- 22877718
TI  - Robotic/Laparoscopic prolapse repair and the role of hysteropexy: a urology
      perspective.
AB  - Approximately 11% of women will undergo a surgical procedure for the treatment of
      pelvic organ prolapse (POP) or urinary incontinence by age 80 years. Abdominal
      sacrocolpopexy has been found in multiple studies to have high long-term success
      rates for repair of severe vault prolapse. Robotic or laparoscopic sacrocolpopexy
      offer similar success to an open approach. This article describes the techniques
      of laparoscopic sacrocolpopexy and robotic sacrocolpopexy. The role of
      hysteropexy for the treatment of POP is also discussed.

PMID- 22877719
TI  - Posterior compartment prolapse: a urogynecology perspective.
AB  - Posterior compartment prolapse is often caused by a defect in the rectovaginal
      septum, also known as Denonvillier's fascia. Patients with symptomatic posterior
      compartment prolapse can present with bulge symptoms as well as defecatory
      dysfunction, including constipation, tenesmus, splinting, and fecal incontinence.
      The diagnosis can successfully be made on clinical examination. Treatment of
      posterior prolapse includes pessaries and surgery. Both traditional colporrhaphy
      and site-specific defect repair have excellent success rates. Complications from
      surgery can include sexual dysfunction, de novo dyspareunia, and defecatory
      dysfunction. Compared with native tissue repair, biological and synthetic
      grafting has not improved overall anatomic and subjective outcomes.

PMID- 22877720
TI  - Posterior-compartment repair: a urology perspective.
AB  - The prevalence of posterior-compartment prolapse (rectocele) is not known. The
      authors have found that operative repair symptomatically improved a majority of
      patients with impaired defecation associated with a large rectocele, but this
      improvement was likely related at least in part to factors other than the size of
      the rectocele. Multiple surgical techniques are available for rectocele repair,
      and the literature is not clear regarding indications for each type of surgical
      intervention. This article reviews the literature regarding various types of
      posterior-compartment repair, and draws conclusions regarding their absolute
      efficacy and relative efficacy in comparison with one another.

PMID- 22877721
TI  - Interstitial cystitis/bladder pain syndrome: management of the pain disorder: a
      urogynecology perspective.
AB  - Our understanding of interstitial cystitis/painful bladder syndrome (IC/BPS) has
      evolved with the advancements in our understanding of visceral pain syndromes.
      The concept of IC/BPS as a visceral pain disorder is used as a model to base a
      targeted approach to the management of patients with IC/BPS. Guidelines for the
      treatment of both the bladder and nonbladder pain disorders are reviewed.

PMID- 22877722
TI  - Management of interstitial cystitis/bladder pain syndrome: a urology perspective.
AB  - Management of interstitial cystitis/bladder pain syndrome (IC/BPS) is
      individualized for each patient. All patients benefit from education and self
      care advice. Patients with Hunner lesions usually respond well to fulguration or
      triamcinolone injection, which can be repeated when the symptoms and lesions
      recur. For patients without Hunner lesions, numerous treatment options are
      available. The tiers of the American Urological Association Guidelines present
      these options in an orderly progression, balancing the benefits, risks, and
      burdens. Along with specific IC/BPS treatments, it is also important to have
      resources for stress reduction, pain management, and treatment of comorbid
      conditions.

PMID- 22877723
TI  - Implantable neuromodulation for urinary urge incontinence and fecal incontinence:
      a urogynecology perspective.
AB  - Implantable sacral nerve stimulation is a minimally invasive, durable, and
      reversible procedure for patients with urinary urge and fecal incontinence who
      are refractory to conservative therapy. The therapy is safe compared with other
      surgical options. An intact external or internal rectal sphincter is not a
      prerequisite for success in patients with fecal incontinence.

PMID- 22877724
TI  - Neuromodulation for voiding dysfunction and fecal incontinence: a urology
      perspective.
AB  - Neuromodulation is an effective, minimally invasive technique for the management
      of urinary urgency and frequency, urgency incontinence, nonobstructive urinary
      retention, and fecal incontinence. This article reviews the physiology of
      neuromodulation, indications, implantation methods, and outcomes.

PMID- 22877725
TI  - Management of mesh complications and vaginal constriction: a urogynecology
      perspective.
AB  - Once thought of as a long-term solution to pelvic organ prolapse, currently
      synthetic mesh augmentation is regarded as a dark area that is being critically
      assessed by surgeons, hospitals, industry, and most importantly the Food and Drug
      Administration. The development of midurethral sling kits has revolutionized the
      surgical treatment of stress incontinence. These systems, however, were not
      rigorously tested but instead marketed after being cleared by the Food and Drug
      Administration through a simple regulatory process using a previously approved
      predescent material. This article reviews the management of mesh complications of
      synthetic slings and mesh used to augment prolapse repair.

PMID- 22877726
TI  - Controversies in the management of mesh-based complications: a urology
      perspective.
AB  - Since the introduction of the synthetic midurethral sling, several transvaginal
      mesh delivery systems have been developed for treating stress incontinence and
      pelvic organ prolapse. Widespread use of these "kits" has introduced a new
      dilemma of mesh-specific complications that female pelvic surgeons must manage.
      Differing treatment techniques have been described and controversy exists as to
      which method is preferred for vaginal mesh extrusion, mesh perforations, pelvic
      pain, and dyspareunia. This article addresses the differing management strategies
      for mesh complications after reconstructive surgery and highlights the available
      literature on the success of each option.

PMID- 22877728
TI  - Social contact patterns and control strategies for influenza in the elderly.
AB  - Despite dramatic increases in influenza vaccination coverage in the elderly
      population over the past 30 years, influenza mortality rates have remained static
      in this age group. Children are believed to be the primary spreaders of diseases
      such as influenza due to their high degree of inter-contact in school settings,
      and several studies have examined control of influenza in the entire population,
      including the elderly, via targeted vaccination of school children. However, such
      vaccination programs are expensive, and fraught with difficulties of public
      perception of what may be seen as an unnecessary vaccination against a disease
      that is normally mild in the children themselves. In the study presented here, we
      examine the control of influenza in the elderly using simple social distancing
      measures during an influenza epidemic. The recent work of Glasser et al.
      characterizes daily contact interactions within the population in terms of
      preferential mixing between age group peers, co-workers, and parents and
      children. We expand upon this to include interactions between grandparents and
      grandchildren, and fit the parameters of this formulation to the recently
      published social contact survey data of Mossong et al. Using this formulation, we
      then model an influenza epidemic with an age-structured deterministic disease
      model and examine how reduction in contacts between grandchildren and
      grandparents affects the spread of influenza to the elderly. We find that over
      50% of all influenza infections in the elderly are caused by direct contact with
      an infected child, and we determine that social distancing between grandparents
      and grandchildren is remarkably effective, and is capable of reducing influenza
      attack rates in the elderly by up to 60%.

PMID- 22877729
TI  - Molecular profiling of peripheral blood cells from patients with polycythemia
      vera and related neoplasms: identification of deregulated genes of significance
      for inflammation and immune surveillance.
AB  - Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis
      (PMF) are hematopoietic stem cell neoplasms that may be associated with
      autoimmune or chronic inflammatory disorders. Earlier gene expression profiling
      studies have demonstrated aberrant expression of genes involved in inflammatory
      responses, mainly being performed on granulocytes or CD34+ cells. Using gene
      expression profiling of whole blood from patients with ET (n=16), PV (n=36), and
      PMF (n=9), several genes involved in inflammation and immune regulation were
      found to be significantly deregulated. Our findings may reflect chronic
      inflammation to be of pathogenetic importance for the progression of these
      neoplasms toward the myelofibrotic end-stage and may also account for the
      increased frequency of second cancer in these diseases.

PMID- 22877730
TI  - Asystole following complex partial seizures.
AB  - A case is presented of a patient with a long history of epilepsy who presents
      with recurrent seizures and develops a period of asystole. The case highlights
      the need to consider the potential arrhythmic complications of seizures and the
      clinical characteristics that may be present in those with epilepsy that may
      warrant evaluation for arrhythmias. 

PMID- 22877731
TI  - Overview: the 2nd Indigenous Cardiovascular Health Conference of the Cardiac
      Society of Australia and New Zealand.
AB  - Recent years have seen the Cardiac Society of Australia and New Zealand (CSANZ)
      focus its attention on improving outcomes for Indigenous people within Australia
      and New Zealand. The most visible of these activities has been the convening of
      conferences devoted specifically to understanding and overcoming the burden of
      cardiovascular disparities experienced by Aboriginal and Torres Strait Islanders
      within Australia and Maori and Pacific Islander populations within New Zealand.
      Following from the success of the first meeting, the second was held in Alice
      Springs in 2011. Alongside plenary sessions discussing primary prevention,
      improved care, secondary prevention and the social and cultural determinants of
      cardiovascular diseases (CVD), targeted workshops outlined the issues and
      priority activities for the CSANZ into the future. These included discussion of
      Workforce, Improving Chronic Care, Reducing the burden of Rheumatic Heart Disease
      and Reducing Disparities in Hospital Care.

PMID- 22877732
TI  - Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian
      target of rapamycin complex 1 pathway.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) pathway is known to couple
      different environmental cues to the regulation of several energy-demanding
      functions within the cell, spanning from protein translation to mitochondrial
      activity. As a result, at the organism level, mTORC1 activity affects energy
      balance and general metabolic homoeostasis by modulating both the activity of
      neuronal populations that play key roles in the control of food intake and body
      weight, as well as by determining storage and use of fuel substrates in
      peripheral tissues. This review focuses on recent advances made in understanding
      the role of the mTORC1 pathway in the regulation of energy balance. More
      particularly, it aims at providing an overview of the status of knowledge
      regarding the mechanisms underlying the ability of certain amino acids, glucose
      and fatty acids, to affect mTORC1 activity and in turn illustrates how the mTORC1
      pathway couples nutrient sensing to the hypothalamic regulation of the organisms'
      energy homoeostasis and to the control of intracellular metabolic processes, such
      as glucose uptake, protein and lipid biosynthesis. The evidence reviewed
      pinpoints the mTORC1 pathway as an integrator of the actions of nutrients on
      metabolic health and provides insight into the relevance of this intracellular
      pathway as a potential target for the therapy of metabolic diseases such as
      obesity and type-2 diabetes.

PMID- 22877733
TI  - Willingness to participate in disaster management among Indian dental graduates.
AB  - INTRODUCTION: India has been the focal point of various disasters, and has
      suffered considerable losses due to the same. Manpower shortage can impede
      disaster management; hence, including dental professionals in disaster management
      in India can be crucial. HYPOTHESIS/PROBLEM: To assess willingness to participate
      in disaster management among Indian dental graduates; to assess the objective
      knowledge, attitude, behavior and perceived knowledge regarding disaster
      management among Indian dental graduates. METHODS: All the interns in Manipal
      College of Dental Sciences, Mangalore, Karnataka were included in the present
      study. Their willingness to participate in disaster management and their
      objective knowledge, attitude, behavior and perceived knowledge related to
      disaster management were assessed using a questionnaire. RESULTS: A total of 86
      study subjects participated. A majority (98.8%) of respondents were willing to
      participate in disaster management. Mean objective knowledge, attitude, behavior
      and perceived knowledge scores were 48.65%, 80.26%, 29.85% and 60.80%
      respectively. Males reported higher perceived knowledge than females (P = .008),
      and respondents residing in hostels reported higher perceived knowledge than
      those not residing in hostels (P = .02). Gender showed significant correlations
      with attitude (r = 4.076, P = .044) and behavior (r = 3.722, P = .054), and
      residence with behavior of respondents (r = 5.690, P = .017). CONCLUSIONS: A high
      degree of willingness to provide assistance during disasters was observed among
      undergraduate dental students. High attitude coupled with low knowledge and
      behavior scores regarding disaster management was also observed. Gender was
      associated with attitude and behavior, and residence with behavior of respondents
      regarding disaster management. Including disaster management in dental curricula
      and involvement of dental professionals in disaster management might be crucial
      for disaster management in India.

PMID- 22877734
TI  - PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.
AB  - Morphine, a potent narcotic analgesic used for the treatment of acute and chronic
      pain, was chemically incorporated into a poly(anhydride-ester) backbone. The
      polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing
      morphine in a controlled manner to ultimately provide analgesia for an extended
      time period. PolyMorphine was synthesized via melt-condensation polymerization
      and its structure was characterized using proton and carbon nuclear magnetic
      resonance spectroscopies, and infrared spectroscopy. The weight-average molecular
      weight and the thermal properties were determined. The hydrolytic degradation
      pathway of the polymer was determined by in vitro studies, showing that free
      morphine is released. In vitro cytocompatibility studies demonstrated that
      PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice
      showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic
      window of free morphine. The animals retained full responsiveness to morphine
      after being subjected to an acute morphine challenge.

PMID- 22877735
TI  - Self-assembled micelles of monosialogangliosides as nanodelivery vehicles for
      taxanes.
AB  - We demonstrate herein that taxanes (paclitaxel (Ptx) and docetaxel (Dtx)) can be
      spontaneously loaded into ganglioside nanomicelles. The efficiency of
      gangliosides to solubilize taxanes was highly dependent on their self-aggregating
      structure. Thus, GM3 that forms unilamellar vesicles was less efficient to
      solubilize taxanes than gangliosides that form micelles (i.e. GM1 and GM2).
      Sialic acid cyclization of GM1 by acid treatment led to an important reduction in
      its capacity to solubilize taxanes, as also did the replacement of the fatty acid
      of ceramide by a dicholoracetyl group. Water solubility of paclitaxel (Ptx) is
      less than 1 MUg mL-1 and increased up to 6.3mg.mL-1 upon its association with GM1
      micelles. The incorporation of Ptx in GM1 reached an optimum at GM1/Ptx 20/1
      molar ratio when performed at room temperature. An increase in the solubilization
      capacity of GM1 micelles was observed upon dehydration of their polar head group
      by pre-treatment at 55  degrees C. Loading of Ptx into the micelle induced a
      structural reorganization that led to an important protection of Ptx reducing its
      hydrolysis at alkaline pH. Diffusion of either GM1 or Ptx was restricted upon
      mixed-micelle formation indicating that they are kinetically more stable than
      pure ganglioside micelles. X-ray powder diffraction of lyophilized GM1 micelles
      with Ptx showed a change in their internal structure from a crystalline state to
      completely amorphous. Taxane-ganglioside mixed micelles were stable in solution
      for at least 4months and also upon freeze-thawing or lyophilization
      solubilization cycles. Upon mixing with human blood constituents, GM1/Ptx
      micelles did not induce hemolysis or platelet aggregation and were spontaneously
      covered with human serum albumin (HSA), which could aid in the delivery of
      micellar content to tumors. In vitro antimitotic activity of GM1/Ptx mixed
      micelles was qualitatively equivalent to that of free drug in DMSO solution.

PMID- 22877737
TI  - Sampling and detection of skin Propionibacterium acnes: current status.
AB  - A connection between acne vulgaris and Propionibacterium acnes has long been
      suggested. Over the years, several human skin microbiota sampling methods have
      been evolved and applied, e.g. swab, scrape, extraction techniques including
      cyanoacrylate gel sampling as well as punch biopsy. Collected samples have been
      processed following various methodologies ranging from culture studies to probe
      labelling and molecular analysis. Direct visualization techniques have recently
      shown the existence of anatomically distinct skin P. acnes populations: epidermal
      and follicular. P. acnes biofilms appear to be a common phenomenon. Current
      sampling approaches target different skin populations of P. acnes and the
      presence of microbial biofilms can influence the retrieval of P. acnes. The
      anatomical considerations must be taken into account while interpreting
      microbiological data.

PMID- 22877738
TI  - Simultaneously preparative purification of Huperzine A and Huperzine B from
      Huperzia serrata by macroporous resin and preparative high performance liquid
      chromatography.
AB  - Huperzine A (HupA) and Huperzine B (HupB) are natural alkaloids existed in
      Lycopodium plants. They both have potential clinical application for treating
      Alzheimer's Disease (AD). For the purpose of better utilizing the limited plant
      resources, a quick and low cost method to separate and purify HupA and HupB from
      Huperzia serrata (Thunb. ex Murray) was established in this paper. Low polarity
      macroporous resin SP850 was selected from eight kinds of resins during initial
      purification. Trifluoroacetic acid (TFA) was proved to be the best acid modifier
      reagent among all acids used in our experiment for improving separation. HupA and
      HupB were baseline separated on a C18 column by preparative high performance
      liquid chromatography (Preparative HPLC), the optimal gradient mobile phase
      system contained methanol increasing from 15% (v/v) to 35% (v/v) and 0.1% (v/v)
      TFA within the water. The purity of HupA and HupB obtained was 99.1% and 98.6%,
      respectively, and the total recovery for them was 83.0% and 81.8%, respectively.

PMID- 22877736
TI  - Comparative genomic analysis of esophageal adenocarcinoma and squamous cell
      carcinoma.
AB  - Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we
      conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12
      esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly,
      inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs.
      There was a substantial disparity in the spectrum of mutations, with more indels
      in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P <
      0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11
      of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found
      that most mutations in EACs were already present in matched Barrett esophagus.
      These discoveries highlight key genetic differences between EACs and ESCCs and
      between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor
      gene in the esophagus. Finally, we provide a genetic basis for the evolution of
      EACs from Barrett esophagus.

PMID- 22877739
TI  - Application of ionic liquid for extraction and separation of bioactive compounds
      from plants.
AB  - In recent years, ionic liquids (ILs), as green and designer solvents, have
      accelerated research in analytical chemistry. This review highlights some of the
      unique properties of ILs and provides an overview of the preparation and
      application of IL or IL-based materials to extract bioactive compounds in plants.
      IL or IL-based materials in conjunction with liquid-liquid extraction (LLE),
      ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE), high
      performance liquid chromatography (HPLC) and solid-phase extraction (SPE)
      analytical technologies etc., have been applied successfully to the extraction or
      separation of bioactive compounds from plants. This paper reviews the available
      data and references to examine the advantages of IL and IL-based materials in
      these applications. In addition, the main target compounds reviewed in this paper
      are bioactive compounds with multiple therapeutic effects and pharmacological
      activities. Based on the importance of the targets, this paper reviews the
      applications of ILs, IL-based materials or co-working with analytical
      technologies. The exploitation of new applications of ILs on the extraction of
      bioactive compounds from plant samples is expected to increase.

PMID- 22877740
TI  - HPTLC and reverse phase HPLC methods for the simultaneous quantification and in
      vitro screening of antioxidant potential of isolated sesquiterpenoids from the
      rhizomes of Cyperus rotundus.
AB  - Three sesquiterpenoids solavetivone, aristolone and nootkatone were isolated from
      the acetone extract of Cyperus rotundus by silica gel column chromatography and
      identified by spectral studies. Solavetivone has been isolated for the first time
      from the species. Simple, sensitive and selective HPTLC and HPLC methods with
      ultraviolet detection (245 nm) were developed and validated for the simultaneous
      quantification. HPTLC method was validated in terms of their linearity, LOD, LOQ,
      precision, accuracy and compared with RP-HPLC-UV method. Among the three
      sesquiterpenoids isolated, nootkatone possessed the highest radical scavenging
      potential (IC(50) 4.81 MUg/ml) followed by aristolone (IC(50) 5.28 MUg/ml) and
      solavetivone (IC(50) 6.82 MUg/ml) by DPPH radical scavenging assay. Total
      antioxidant activity against phosphomolybdenum reagent was also studied. The
      methods described in this paper were able to identify and quantify
      sesquiterpenoids from the complex mixtures of phytochemicals and could be
      extended to the marker based standardization of polyherbal formulations
      containing C. rotundus.

PMID- 22877741
TI  - Impact assessment of excess discharges of organics and nutrients into aquatic
      systems by thermodynamic entropy calculation.
AB  - In this study, a method was proposed for calculating the thermodynamic entropy
      increase DeltaS in a water body after receiving excess discharge of organics and
      nutrients in order to quantitatively assess the impact of pollutants discharge on
      aquatic systems. The enthalpy change was evaluated using the standard
      thermodynamic data according to the possible chemical and/or biochemical
      reactions such as organic oxidation, nitrification/denitrification, and
      phosphorus precipitation, for the recovery of water quality to the background
      level. A series of equations were established for calculating the DeltaS
      associated with the decomposition or removal of TOC, NO(3)-N, NO(2)-N, NH(3)-N
      and TP. The values of DeltaS corresponding to unit mass (per g) of these
      pollutants were calculated as 54.0 kJ/K, 2.91 kJ/K, 10.01 kJ/K, 28.51 kJ/K and
      2.81 kJ/K, respectively. Besides, the applicability of the proposed method was
      proved by a scenario analysis regarding effluent quality control and surface
      water quality protection in China.

PMID- 22877742
TI  - Quantifying changes in flooding and habitats in the Tonle Sap Lake (Cambodia)
      caused by water infrastructure development and climate change in the Mekong
      Basin.
AB  - The economic value of the Tonle Sap Lake Floodplain to Cambodia is arguably among
      the highest provided to a nation by a single ecosystem around the world.
      Nonetheless, the Mekong River Basin is changing rapidly due to accelerating water
      infrastructure development (hydropower, irrigation, flood control, and water
      supply) and climate change, bringing considerable modifications to the flood
      pulse of the Tonle Sap Lake in the foreseeable future. This paper presents
      research conducted to determine how the historical flooding regime, together with
      human action, influenced landscape patterns of habitats in the Tonle Sap Lake,
      and how these habitats might shift as a result of hydrological changes. Maps of
      water depth, annual flood duration, and flood frequency were created for recent
      historical hydrological conditions and for simulated future scenarios of water
      infrastructure development and climate change. Relationships were then
      established between the historical flood maps and land cover, and these were
      subsequently applied to assess potential changes to habitat cover in future
      decades. Five habitat groups were clearly distinguishable based on flood regime,
      physiognomic patterns, and human activity: (1) Open water, flooded for 12 months
      in an average hydrological year; (2) Gallery forest, with flood duration of 9
      months annually; (3) Seasonally flooded habitats, flooded 5-8 months and
      dominated by shrublands and grasslands; (4) transitional habitats, flooded 1-5
      months and dominated by abandoned agricultural fields, receding rice/floating
      rice, and lowland grasslands; and (5) Rainfed habitats, flooded up to 1 month and
      consisting mainly of wet season rice fields and village crops. It was found that
      water infrastructure development could increase the area of open water (+18 to
      +21%) and the area of rainfed habitats (+10 to +14%), while reducing the area
      covered with seasonally flooded habitats (-13 to -22%) and gallery forest (-75 to
      -83%). Habitat cover shifts as a result of climate change include a net increase
      of open water (2-21%), as well as a reduction of rainfed habitats by 2-5% and
      seasonally flooded habitats by 5-11%. Findings from this study will help guide on
      going and future conservation and restoration efforts throughout this unique and
      critical ecosystem.

PMID- 22877743
TI  - A decision support model for improving a multi-family housing complex based on
      CO2 emission from electricity consumption.
AB  - The number of deteriorated multi-family housing complexes in South Korea
      continues to rise, and consequently their electricity consumption is also
      increasing. This needs to be addressed as part of the nation's efforts to reduce
      energy consumption. The objective of this research was to develop a decision
      support model for determining the need to improve multi-family housing complexes.
      In this research, 1664 cases located in Seoul were selected for model
      development. The research team collected the characteristics and electricity
      energy consumption data of these projects in 2009-2010. The following were
      carried out in this research: (i) using the Decision Tree, multi-family housing
      complexes were clustered based on their electricity energy consumption; (ii)
      using Case-Based Reasoning, similar cases were retrieved from the same cluster;
      and (iii) using a combination of Multiple Regression Analysis, Artificial Neural
      Network, and Genetic Algorithm, the prediction performance of the developed model
      was improved. The results of this research can be used as follows: (i) as basic
      research data for continuously managing several energy consumption data of multi
      family housing complexes; (ii) as advanced research data for predicting energy
      consumption based on the project characteristics; (iii) as practical research
      data for selecting the most optimal multi-family housing complex with the most
      potential in terms of energy savings; and (iv) as consistent and objective
      criteria for incentives and penalties.

PMID- 22877744
TI  - Adaptive terminal sliding-mode control strategy for DC-DC buck converters.
AB  - This paper presents an adaptive terminal sliding mode control (ATSMC) strategy
      for DC-DC buck converters. The idea behind this strategy is to use the terminal
      sliding mode control (TSMC) approach to assure finite time convergence of the
      output voltage error to the equilibrium point and integrate an adaptive law to
      the TSMC strategy so as to achieve a dynamic sliding line during the load
      variations. In addition, the influence of the controller parameters on the
      performance of closed-loop system is investigated. It is observed that the start
      up response of the output voltage becomes faster with increasing value of the
      fractional power used in the sliding function. On the other hand, the transient
      response of the output voltage, caused by the step change in the load, becomes
      faster with decreasing the value of the fractional power. Therefore, the value of
      fractional power is to be chosen to make a compromise between start up and
      transient responses of the converter. Performance of the proposed ATSMC strategy
      has been tested through computer simulations and experiments. The simulation
      results of the proposed ATSMC strategy are compared with the conventional SMC and
      TSMC strategies. It is shown that the ATSMC exhibits a considerable improvement
      in terms of a faster output voltage response during load changes.

PMID- 22877745
TI  - Can spinal cord stimulation reduce ventricular arrhythmias?

PMID- 22877746
TI  - No penetration of nanoparticles through intact skin.

PMID- 22877747
TI  - Fatty acid synthase inhibitor orlistat induces apoptosis in T cell lymphoma: role
      of cell survival regulatory molecules.
AB  - BACKGROUND: De novo fatty acid synthesis catalyzed by fatty acid synthase (FASN)
      is crucial for tumor cell survival. Thus therapeutic targeting of FASN is
      considered as a novel antineoplastic strategy. However, little is understood in
      this respect regarding malignancies of hematological origin. The present
      investigation was therefore, undertaken to study the molecular mechanisms of the
      antitumor action of FASN inhibitor orlistat (tetrahydrolipstatin) using a murine
      model of a T cell lymphoma. METHODS: The antitumor efficacy of orlistat was
      investigated in vitro by estimating cell survival by MTT assay and apoptosis by
      Wright Giemsa, TUNEL, Annexin-V/PI staining and % DNA fragmentation. Generation
      of reactive oxygen species (ROS) in tumor cells was studied using fluorescence
      microscopy. Expression of genes and proteins was carried out by RT-PCR and
      western blot analyses respectively. FASN and CPT-1 activity was estimated by
      spectrophotometer. Cytokines expression was analyzed by ELISA. RESULTS: We report
      that inhibition of FASN with its specific inhibitor orlistat manifests tumor
      specific inhibition of cell survival, accompanied by induction of apoptosis.
      Orlistat-treated tumor cells showed an altered ROS generation, shift in cytokine
      balance and modulated expression of cell survival regulatory molecules like
      HSP70, Bcl2, p53, PUMA, Caspase-3 and CAD. It was observed that IFN-gamma
      mediates orlistat-dependent modulation of FASN expression. CONCLUSION AND GENERAL
      SIGNIFICANCE: In this study, we report some of the so far unexplored novel
      aspects underlying the molecular mechanisms associated with orlistat-dependent
      modulation of tumor cell survival. These observations will help in designing
      antineoplastic therapeutic protocols using orlistat against malignancies of
      hematological origin.

PMID- 22877748
TI  - Monitoring the occurrence of emerging contaminants in treated wastewater and
      groundwater between 2008 and 2010. The Baix Llobregat (Barcelona, Spain).
AB  - The occurrence of 166 emerging compounds and four heavy metals (Cd, Ni, Hg and
      Pb) in treated wastewater and groundwater has been monitored at the Llobregat
      delta (Barcelona, Spain) over a period of 3 years. Selected compounds were
      pharmaceuticals, personal care products (PCPs), dioxins, polycyclic aromatic
      hydrocarbons (PAHs) and priority substances included in the 2008/105/CE
      Directive. Analysis was performed in tertiary treated wastewater (TWW), after an
      additional treatment of ultrafiltration reverse osmosis and UV disinfection, and
      groundwater from a deep confined aquifer. This aquifer is artificially recharged
      with TWW through injection wells. After the advanced treatment, 38
      pharmaceuticals, 9 PCPs, 9 pesticides and 7 PAHs still showed a frequency of
      detection higher than 25% in the TWW, although at low concentration levels
      (ng/l). Not all active compounds found in the TWW were present in groundwater,
      indicating possible degradation within the aquifer media after the injection. A
      number of chemicals, mainly 10 pesticides and 10 pharmaceuticals were only
      present in groundwater samples, confirming a different origin than the injected
      TWW, probably agricultural activities and/or infiltration of poorly treated
      wastewater.

PMID- 22877749
TI  - BMI-based approach reveals direct impact of metal dust exposure on influenza
      associated lung function decrement risk in smelters.
AB  - Metal dust exposure strongly affects human health, especially for smelters.
      Little is known, however, about the impact of metal dust exposure on influenza
      associated lung function decrement risk in smelters. Different body mass index
      (BMI) groups were also associated with respiratory diseases. The purpose of this
      study was to use a probabilistic risk assessment approach to explicitly link
      occupational metal dust exposure, BMI-correlated health effects, and influenza
      associated lung function decrements to investigate potential risk among smelters.
      Here we showed that (i) influenza A-associated metal dust exposure in
      SiMn/FeMn/FeCr smelters had slightly higher health risks than that in FeSi/Si
      metal's, (ii) BMI>=35 had the highest risk in respiratory infection
      exacerbations, and (iii) the estimated smelting metal dust induced forced
      expiratory volume in 1s (FEV(1)) decreasing rates were 0.59 and 1.11 m(3) mg(-1)
      for FeSi/Si-metal and SiMn/FeMn/FeCr smelters, respectively. Our results
      suggested that smelters better be aware of severe weight gains (e.g., BMIs from
      27-40) because it is likely to lead to 17-25% decrements in lung function. This
      study provides a novel probabilistic risk assessment framework to quantitatively
      assess the occupational health risk posed by metal dust exposure associated with
      influenza infection based on BMI measures.

PMID- 22877750
TI  - Structural properties of metal-free apometallothioneins.
AB  - The metalated forms of metallothionein are well studied (particularly Zn-MT, Cu
      MT and Cd-MT), but almost nothing is known about the chemical and structural
      properties of apometallothioneins despite their importance in initial metalation
      and subsequent demetalation. Electrospray ionization mass spectrometry was used
      to provide a detailed view of the structural properties of the metal-free
      protein. Mass spectra of Zn(7)-MT and apo-MT at pH 7 exhibit the same charge
      state distribution, indicating that apo-MT is tightly folded like the metallated
      protein, whereas apo-MT at pH 3 exhibits a charge state spectrum associated with
      unfolding or denaturation. Benzoquinone was used to modify the cysteines in the
      beta-MT (9 Bq), and alpha-MT (11 Bq) fragments, and the full betaalpha-MT (20 Bq)
      protein. ESI-MS showed that the overall volume and, therefore, the extent of
      folding for the modified proteins is similar to that of Zn-MT. Molecular modeling
      using MM3-MD methods provided the volume of each modified protein. The volumes of
      the partially modified proteins follow the same trend as the charge states,
      showing that ESI-MS is an excellent method with which to follow small changes in
      protein folding as a function of applied chemical stress. The data suggest that
      the structure of apo-betaalpha-MT is more organized than previously considered.

PMID- 22877751
TI  - Rare sugar D-psicose protects pancreas beta-islets and thus improves insulin
      resistance in OLETF rats.
AB  - Rare sugar D-psicose has cropped up as a non-toxic and effective compound to
      protect and preserve pancreatic beta-islets in the growing type 2 diabetes
      mellitus (T2DM) rats through the regulation of glucose and fat metabolism. The
      present study was undertaken to examine the effect of rare sugar D-psicose on the
      protection of pancreatic beta-islets using Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats, a T2DM model. Treated rats were fed with 5% D-psicose or 5% D
      glucose supplemented drinking water, and only water in the control for 13 weeks.
      A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a
      counter control of OLETF. D-Psicose significantly attenuated progressive beta
      islet fibrosis and preserved islets, evaluated by hematoxylin-eosin staining,
      Masson's trichrome staining and immunostainings of insulin and alpha-smooth
      muscle actin (SMA). D-Psicose significantly reduced increase in body weight and
      abdominal fat deposition. Oral glucose tolerance test (OGTT) showed reduced blood
      glucose levels suggesting the improvement of insulin resistance. All these data
      suggests that D-psicose protected and preserved pancreatic beta-islets through
      the maintenance of hyperglycemia and by the prevention of fat accumulation in
      OLETF rats.

PMID- 22877752
TI  - Identification of hepatocyte growth factor activator (Hgfac) gene as a target of
      HNF1alpha in mouse beta-cells.
AB  - HNF1alpha is a transcription factor that is expressed in pancreatic beta-cells
      and mutations of the HNF1alpha gene cause a form of monogenic diabetes. To
      understand the role of HNF1alpha in pancreatic beta-cells, we established the
      MIN6 beta-cell line that stably expressed HNF1alpha-specific shRNA. Expression of
      the gene encoding hepatocyte growth factor (HGF) activator (Hgfac), a serine
      protease that efficiently activates HGF, was decreased in HNF1alpha KD-MIN6
      cells. Down-regulation of Hgfac expression was also found in the islets of
      HNF1alpha (+/-) mice. Reporter gene analysis and the chromatin
      immunoprecipitation assay indicated that HNF1alpha directly regulates the
      expression of Hgfac in beta-cells. It has been reported that HGF has an important
      influence on beta-cell mass and beta-cell function. Thus, HNF1alpha might
      regulate beta-cell mass or function at least partly by modulating Hgfac
      expression.

PMID- 22877753
TI  - A P39R mutation at the N-terminal domain of human alphaB-crystallin regulates its
      oligomeric state and chaperone-like activity.
AB  - Recent structure analyses of alphaB-crystallin have proposed some models of the N
      terminal domain and the manner of oligomerization, whereas the effects of the
      significantly high content of Pro residues at the N-terminal domain remain
      unclear. We report the properties of a novel P39R mutant of alphaB-crystallin.
      The content of alpha-helix was increased, and the molecular size of the P39R
      mutant was larger than that of wild-type alphaB-crystallin. A slight loss of
      chaperone-like activity was observed using alcohol dehydrogenase (ADH), while a
      significant increase was detected by insulin assay. The Pro residue at the N
      terminal domain of alphaB-crystallin is important for oligomerization and
      function.

PMID- 22877754
TI  - IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway.
AB  - Cellular senescence is characterized by growth arrest, enlarged and flattened
      cell morphology, the expression of senescence-associated beta-galactosidase (SA
      beta-gal), and by activation of tumor suppressor networks. Insulin-like growth
      factor-I (IGF-I) plays a critical role in cellular growth, proliferation,
      tumorigenesis, and regulation of aging. In the present study, we show that IGF-I
      enhances cellular senescence in mouse, rat, and human primary cells in the
      confluent state. IGF-I induced expression of a DNA damage marker, gammaH2AX, the
      increased levels of p53 and p21 proteins, and activated SA-beta-gal. In the
      confluent state, an altered downstream signaling of IGF-I receptor was observed.
      Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC)
      significantly suppressed induction of these markers, indicating that ROS are
      involved in the induction of cellular senescence by IGF-I. In p53-null mouse
      embryonic fibroblasts, the IGF-I-induced augmentation of SA-beta-gal and p21 was
      inhibited, demonstrating that p53 is required for cellular senescence induced by
      IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular
      senescence in the ROS and p53-dependent manner and may explain the underlying
      mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

PMID- 22877755
TI  - Triparanol suppresses human tumor growth in vitro and in vivo.
AB  - Despite the improved contemporary multidisciplinary regimens treating cancer,
      majority of cancer patients still suffer from adverse effects and relapse,
      therefore posing a significant challenge to uncover more efficacious molecular
      therapeutics targeting signaling pathways central to tumorigenesis. Here, our
      study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can
      block proliferation and induce apoptosis in multiple human cancer cells including
      lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth
      inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we
      have proved Triparanol can significantly repress Hedgehog pathway signaling in
      these human cancer cells. Furthermore, study in a mouse xenograft model of human
      lung cancer has validated that Triparanol can impede tumor growth in vivo. We
      have therefore uncovered Triparanol as potential new cancer therapeutic in
      treating multiple types of human cancers with deregulated Hedgehog signaling.

PMID- 22877756
TI  - Effect of enhanced Renilla luciferase and fluorescent protein variants on the
      Forster distance of Bioluminescence resonance energy transfer (BRET).
AB  - Bioluminescence resonance energy transfer (BRET) is an important tool for
      monitoring macromolecular interactions and is useful as a transduction technique
      for biosensor development. Forster distance (R(0)), the intermolecular separation
      characterized by 50% of the maximum possible energy transfer, is a critical BRET
      parameter. R(0) provides a means of linking measured changes in BRET ratio to a
      physical dimension scale and allows estimation of the range of distances that can
      be measured by any donor-acceptor pair. The sensitivity of BRET assays has
      recently been improved by introduction of new BRET components, RLuc2, RLuc8 and
      Venus with improved quantum yields, stability and brightness. We determined R(0)
      for BRET(1) systems incorporating novel RLuc variants RLuc2 or RLuc8, in
      combination with Venus, as 5.68 or 5.55 nm respectively. These values were
      approximately 25% higher than the R(0) of the original BRET(1) system. R(0) for
      BRET(2) systems combining green fluorescent proteins (GFP(2)) with RLuc2 or RLuc8
      variants was 7.67 or 8.15 nm, i.e. only 2-9% greater than the original BRET(2)
      system despite being ~30-fold brighter.

PMID- 22877757
TI  - RNA-binding properties and RNA chaperone activity of human peroxiredoxin 1.
AB  - Human peroxiredoxin 1 (hPrx1), a member of the peroxiredoxin family, detoxifies
      peroxide substrates and has been implicated in numerous biological processes,
      including cell growth, proliferation, differentiation, apoptosis, and redox
      signaling. To date, Prx1 has not been implicated in RNA metabolism. Here, we
      investigated the ability of hPrx1 to bind RNA and act as an RNA chaperone. In
      vitro, hPrx1 bound to RNA and DNA, and unwound nucleic acid duplexes. hPrx1 also
      acted as a transcription anti-terminator in an assay using an Escherichia coli
      strain containing a stem-loop structure upstream of the chloramphenicol
      resistance gene. The overall cellular level of hPrx1 expression was not increased
      at low temperatures, but the nuclear level of hPrx1 was increased. In addition,
      hPrx1 overexpression enhanced the survival of cells exposed to cold stress,
      whereas hPrx1 knockdown significantly reduced cell survival under the same
      conditions. These findings suggest that hPrx1 may perform biological functions as
      a RNA-binding protein, which are distinctive from known functions of hPrx1 as a
      reactive oxygen species scavenger.

PMID- 22877758
TI  - [Knotting of a pulmonary artery catheter].

PMID- 22877759
TI  - [Electrocardiographic changes during stress test in a patient with a type 1
      Brugada electrocardiogram pattern: a curiosity with a clinical implication].

PMID- 22877761
TI  - Women's experiences of gestational diabetes self-management: a qualitative study.
AB  - OBJECTIVE: to explore women's experiences of self-managing their gestational
      diabetes. DESIGN AND PARTICIPANTS: the study design was informed by interpretive
      phenomenological analysis. Data was collected using semi-structured interviews
      and one focus group. Participants included 15 women with a diagnosis of
      gestational diabetes who had experienced self-management of their condition.
      RESULTS: incremental adjustment occurred over 4 discrete themes, including: (1)
      the shock of diagnosis; (2) coming to terms with GDM; (3) working it out/learning
      new strategies; (4) looking to the future. Each adjustment phase was underpinned
      by the fifth theme (5) having a supportive environment. Throughout, participants
      reported that thinking about the baby was a powerful motivator for adherence to
      gestational diabetes management regimens. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: this study has shown that women undergo a process of adjustment
      following GDM diagnosis as they learn to self-manage their condition. The process
      is largely facilitated by the women's interest in maximising fetal health which
      may make them receptive to interventions to improve GDM control and to prevent
      type 2 diabetes in the future.

PMID- 22877762
TI  - Going public: do risk and choice explain differences in caesarean birth rates
      between public and private places of birth in Australia?
AB  - BACKGROUND: women who birth in private facilities in Australia are more likely to
      have a caesarean birth than women who birth in public facilities and these
      differences remain after accounting for sector differences in the demographic and
      health risk profiles of women. However, the extent to which women's preferences
      and/or freedom to choose their mode of birth further account for differences in
      the likelihood of caesarean birth between the sectors remains untested. METHOD:
      women who birthed in Queensland, Australia during a two-week period in 2009 were
      mailed a self-report survey approximately 3 months after birth. Seven hundred and
      fifty-seven women provided cross-sectional retrospective data on where they
      birthed (public or private facility), mode of birth (vaginal or caesarean) and
      risk factors, along with their preferences and freedom to choose their mode of
      birth. A hierarchical logistic regression was conducted to determine the extent
      to which maternal risk and freedom to choose one's mode of birth explain sector
      differences in the likelihood of having a caesarean birth. FINDINGS: while there
      was no sector difference in women's preference for mode of birth, women who
      birthed in private facilities had higher odds of feeling able to choose either a
      vaginal or caesarean birth, and feeling able to choose only a caesarean birth.
      Women had higher odds of having caesarean birth if they birthed in private
      facilities, even after accounting for significant risk factors such as age, body
      mass index, previous caesarean and use of assisted reproductive technology.
      However, there was no association between place of birth and odds of having a
      caesarean birth after also accounting for freedom to choose one's mode of birth.
      CONCLUSIONS: these findings call into question suggestions that the higher
      caesarean birth rate in the private sector in Australia is attributable to
      increased levels of obstetric risk among women birthing in the private sector or
      maternal preferences alone. Instead, the determinants of sector differences in
      the likelihood of caesarean births are complex and are linked to differences in
      the perceived choices for mode of birth between women birthing in the private and
      public systems.

PMID- 22877763
TI  - Perceptions and uses of plants for reproductive health among traditional midwives
      in Ecuador: moving towards intercultural pharmacological practices.
AB  - Despite the fact that plants have played an important role in midwifery in many
      cultures, there are very few in-depth studies on the plants traditionally used by
      midwives. The aim of this study is to analyse the perceptions and the uses of
      medicinal plants for reproductive health among indigenous midwives in the city of
      Otavalo, Ecuador. The article also aims to analyse the perceptions of traditional
      midwives regarding allopathic drugs for reproductive health and their possible
      overlapping uses of medicinal plants and allopathic drugs. The data are drawn
      from an ethnographic study carried out in Ecuador. In total, 20 traditional
      midwives have been interviewed. Individual and in-depth interviews also took
      place with a sample of 35 women as well as with five nurses and two doctors
      working at San Luis Hospital in Otavalo. The study shows that cultural health
      management and the incorporation of the beliefs and practices relating to women's
      reproductive health can represent a starting point towards the search for more
      successful strategies in reproductive health.

PMID- 22877764
TI  - Mother knows best: developing a consumer led, evidence informed, research agenda
      for maternity care.
AB  - The principles of evidence-based practice and involvement of consumers in
      healthcare are well established. However, consumers are rarely involved in
      decisions about what evidence is actually required and this may result in a
      mismatch between research undertaken and issues of importance to those who use
      the health services. This may be particularly evident in maternity care where
      disease focused research funding priorities may not address aspects of care which
      are important to the majority of women. Working with service users to generate
      possible future research questions may facilitate more women centred research.
      AIM:  METHOD: the project used a three stage participatory approach in a diverse
      sample of localities across Scotland. Twelve pre-existing, community-based groups
      of maternity service users participated with between 8 and 20 mothers in each.
      Each group met twice. At the first meeting group discussion identified topics and
      questions. A rapid literature review of each topic was conducted and used to
      develop a document summarising evidence to facilitate discussion at the second
      meeting. The group then prioritised topic areas and questions using a modified
      Nominal Group Technique. FINDINGS: analysis identified key topics and questions
      which were raised and prioritised by a number of the groups; a 'top ten' list of
      priority topics was readily identified, these included aspects of postnatal care,
      antenatal care, communication and information giving and risk. Approximately 200
      individual questions were asked by women, for example: What is the impact of a
      bad birth experience on postnatal physical and psychological health? What is the
      best way of providing antenatal classes/preparation classes? What is the effect
      of women feeling not listened to in labour? How can fathers be given effective
      preparation for coping with labour and birth and supporting their partner?
      DISCUSSION: this project demonstrates that women are well able to articulate
      researchable questions when given the opportunity and support to do so. Although
      a wide range of topics and questions were identified there were remarkable areas
      of consensus and clear areas of priority for women, these should be used to
      inform development of women centred research.

PMID- 22877765
TI  - Towards a relational model of decision-making in midwifery care.
AB  - OBJECTIVE: current individualistic ideas of autonomy and decision making do not
      fit within the context of decision-making in the midwife-woman relationship. This
      article critically explores current issues around decision-making and proposes a
      relational decision-making model for midwifery care. DESIGN: qualitative prenatal
      and postnatal interviews around decision-making within childbirth in general, and
      the third stage of labour in particular. PARTICIPANTS: eight midwife-woman pairs
      in urban settings in New Zealand. FINDINGS: a range of relational, social and
      political factors that are not present within existing decision-making models
      were highlighted. The themes included ontological and philosophical influences on
      decision-making; uncertainty, vulnerability and relational trust; and socio
      political and cultural influences. Inconsistencies in knowledge arising from
      social, cultural and familial considerations as well as identities, beliefs,
      values, conversations, and practices were found to produce uncertainties around
      potential courses of action, expected consequences and outcomes. 'Unplanned'
      birth experiences decreased client autonomy and increased vulnerability thereby
      intensifying relational trust within decision-making. The political context may
      also open up or close down possibilities for decision-making at both national and
      local levels. CONCLUSION: decision-making for women and midwives is influenced by
      complex human, contextual and political factors. This study supports a relational
      model of decision-making that is embedded in understandings of choice as
      'entangled'. A relational model enables consideration of how factors such as
      identity projects, individual practices, the organisation of maternity care,
      local hospital cultures, medicalised childbirth, workforce shortages, funding
      cuts and poverty shape the way in which care decisions are made.

PMID- 22877766
TI  - Optimisation of imipenem regimens in patients with impaired renal function by
      pharmacokinetic-pharmacodynamic target attainment analysis of plasma and urinary
      concentration data.
AB  - In this study, a pharmacokinetic-pharmacodynamic (PK-PD) target attainment
      analysis of imipenem (IPM) in patients with impaired renal function was
      conducted. IPM (500 mg) was administered via a 0.5-h or 1-h infusion to 27
      patients with varying renal function. A population PK model was developed by
      simultaneously fitting plasma and urinary concentration data. A two-compartment
      model adequately described IPM pharmacokinetics, and creatinine clearance
      (CL(Cr)) was identified as the most significant covariate. A PK-PD simulation
      predicted the probabilities of attaining the target in plasma [40% of the time
      above the minimum inhibitory concentration (MIC)] and defined the PK-PD
      breakpoints (the highest MICs at which the probabilities were >=90%). In a
      patient with a CL(Cr) of 90 mL/min, prolongation of infusion time (from 0.5 h to
      1.5 h) increased the PK-PD breakpoint from 1 MUg/mL to 2 MUg/mL with a 500 mg
      dose every 8h (q8h) and from 2 MUg/mL to 4 MUg/mL with a 500 mg dose every 6h
      (q6h). Meanwhile, in a patient with a CL(Cr) of 20 mL/min, the PK-PD breakpoints
      for both 0.5-h and 1.5-h infusions were 1 MUg/mL with a 250 mg dose every 12h
      (q12h), 2 MUg/mL with a 250 mg dose q8h and a 500 mg dose q12h, and 4 MUg/mL with
      a 250 mg dose q6h. These results indicate that a shorter dosing interval is
      beneficial in patients with impaired renal function as it results in greater PK
      PD breakpoints and a reduction in excessive maximum plasma concentrations. These
      results help to optimise IPM regimens, particularly in patients with impaired
      renal function.

PMID- 22877767
TI  - Serving size guidance for consumers: is it effective?
AB  - Larger portion sizes (PS) may be inciting over-eating and contributing to obesity
      rates. Currently, there is a paucity of data on the effectiveness of serving size
      (SS) guidance. The aims of the present review are to evaluate SS guidance; the
      understanding, usability and acceptability of such guidance, its impact on
      consumers and potential barriers to its uptake. A sample of worldwide SS guidance
      schemes (n 87) were identified using targeted and untargeted searches, overall
      these were found to communicate various inconsistent and often conflicting
      messages about PS selection. The available data suggest that consumers have
      difficulty in understanding terms such as 'portion size' and 'serving size', as
      these tend to be used interchangeably. In addition, discrepancies between
      recommended SS and those present on food labels add to the confusion. Consumers
      generally understand and visualise SS best when expressed in terms of household
      measures rather than actual weights. Only a limited number of studies have
      examined the direct impact of SS guidance on consumer behaviour with equivocal
      results. Although consumers recognise that guidance on selecting SS would be
      helpful, they are often unwilling to act on such guidance. The challenge of
      achieving consumer adherence to SS guidance is formidable due to several barriers
      including chronic exposure to larger PS, distorted consumption norms and
      perceptions, the habit of 'cleaning one's plate' and language barriers for ethnic
      minorities. In conclusion, the impact of SS guidance on consumers merits further
      investigation to ensure that future guidance resonates with consumers by being
      more understandable, usable and acceptable.

PMID- 22877770
TI  - A solid quality-control analysis of AB SOLiD short-read sequencing data.
AB  - Next generation sequencers have greatly improved our ability to mine
      polymorphisms and mutations out of entire (or portions of) genomes. The
      reliability of their outputs, though, showed to be very related to the sequencing
      chemistry and to deeply affect the quality of the downstream analyses. We focus
      here on the two-base color code chemistry of AB SOLiD sequencers and propose a
      comprehensive quality control methodological and software pipeline. We used
      existing and custom tools to detect and purge short-reads of some common flaws
      due to sequencing errors and chemical hitches. We apply them to a cohort of SOLiD
      4 runs and measure their joint efficacy in terms of the resulting ability to
      detect the greatest possible number of true variants. 

PMID- 22877768
TI  - Network-based drug discovery by integrating systems biology and computational
      technologies.
AB  - Network-based intervention has been a trend of curing systemic diseases, but it
      relies on regimen optimization and valid multi-target actions of the drugs. The
      complex multi-component nature of medicinal herbs may serve as valuable resources
      for network-based multi-target drug discovery due to its potential treatment
      effects by synergy. Recently, robustness of multiple systems biology platforms
      shows powerful to uncover molecular mechanisms and connections between the drugs
      and their targeting dynamic network. However, optimization methods of drug
      combination are insufficient, owning to lacking of tighter integration across
      multiple '-omics' databases. The newly developed algorithm- or network-based
      computational models can tightly integrate '-omics' databases and optimize
      combinational regimens of drug development, which encourage using medicinal herbs
      to develop into new wave of network-based multi-target drugs. However, challenges
      on further integration across the databases of medicinal herbs with multiple
      system biology platforms for multi-target drug optimization remain to the
      uncertain reliability of individual data sets, width and depth and degree of
      standardization of herbal medicine. Standardization of the methodology and
      terminology of multiple system biology and herbal database would facilitate the
      integration. Enhance public accessible databases and the number of research using
      system biology platform on herbal medicine would be helpful. Further integration
      across various '-omics' platforms and computational tools would accelerate
      development of network-based drug discovery and network medicine. 

PMID- 22877769
TI  - Application of next generation sequencing to human gene fusion detection:
      computational tools, features and perspectives.
AB  - Gene fusions are important genomic events in human cancer because their fusion
      gene products can drive the development of cancer and thus are potential
      prognostic tools or therapeutic targets in anti-cancer treatment. Major
      advancements have been made in computational approaches for fusion gene discovery
      over the past 3 years due to improvements and widespread applications of high
      throughput next generation sequencing (NGS) technologies. To identify fusions
      from NGS data, existing methods typically leverage the strengths of both
      sequencing technologies and computational strategies. In this article, we review
      the NGS and computational features of existing methods for fusion gene detection
      and suggest directions for future development. 

PMID- 22877771
TI  - Other methods of axillary assessment and their value.

PMID- 22877772
TI  - The mysteries of the diatoms.
AB  - Understanding the physiology of these unique and spectacularly successful algal
      species could lead to substantial benefits in a wide range of areas from
      nanotechnology to climate change. Michael Gross reports.

PMID- 22877773
TI  - Cheese microbes.

PMID- 22877774
TI  - Low genetic diversity in tepui summit vertebrates.

PMID- 22877775
TI  - Preservation of musical memory in an amnesic professional cellist.

PMID- 22877776
TI  - Origin of land plants revisited in the light of sequence contamination and
      missing data.

PMID- 22877777
TI  - Visual transduction: microvilli orchestrate photoreceptor responses to light.
AB  - How do the microscopic properties of a photoreceptor shape the transformation of
      photon inputs into electrical outputs? Adaptive feedback, combined with
      stochastic sampling of light by transduction units, efficiently captures visual
      information.

PMID- 22877778
TI  - Endocytic traffic: vesicle fusion cascade in the early endosomes.
AB  - New research shows that vesicles in the early endosomal network coalesce
      according to a classical theoretical description of aggregation put forward by
      Smoluchowski more than 100 years ago. This gives a new tool for unraveling
      complexities of the endocytic pathways.

PMID- 22877779
TI  - Brain connectivity: the feel of blindsight.
AB  - A visual subcortical pathway to the amygdala that undergoes structural plastic
      strengthening in blindsight has been identified in humans - neuroanatomical
      evidence for a pathway that might mediate rapid non-conscious processing of
      salient information.

PMID- 22877780
TI  - Prokaryotic sex: eukaryote-like qualities of recombination in an Archaean
      lineage.
AB  - Genetic exchange within one Archaean lineage is a bit like sex in eukaryotes -
      cells fuse and huge segments of DNA are recombined - with consequences for the
      spread of adaptations across species.

PMID- 22877781
TI  - Membrane abscission: first glimpse at dynamic ESCRTs.
AB  - Advanced live-cell imaging of the endosomal sorting complexes required for
      transport (ESCRT) and computational modeling have provided insights into the Vps4
      dependent dynamic rearrangements of ESCRT-III filaments during membrane
      constriction and abscission.

PMID- 22877782
TI  - Blindsight: spontaneous scanning of complex scenes.
AB  - A new study of monkeys with blindsight has provided some surprising new insights
      into the visual properties that remain salient without a functioning primary
      visual cortex and may help improve rehabilitation strategies used with human
      hemianopes.

PMID- 22877783
TI  - Molecular motors: a finicky myosin V chooses its own path.
AB  - Cytoskeletal trafficking systems are becoming more complex at every turn. A new
      study reports that a yeast myosin V walks on only a select few actin filaments -
      those that are decorated with tropomyosin.

PMID- 22877784
TI  - Retroviruses and the placenta.
AB  - Retroviruses are often expressed in the placenta. Placental expression probably
      evolved to facilitate retroviral transmission from mother to offspring and from
      offspring to mother. In the process, the placenta became a site where retroviral
      genes were 'domesticated' to serve adaptive functions in the host, including the
      manipulation of maternal physiology for the benefit of the fetus. The
      evolutionary interplay between retroviruses and host defenses may have
      contributed to the remarkable diversity of form among mammalian placentas and to
      mechanisms of genomic imprinting.

PMID- 22877785
TI  - Food restriction, ghrelin, its antagonist and obestatin control expression of
      ghrelin and its receptor in chicken hypothalamus and ovary.
AB  - The purpose of the present study was to identify the role of age, nutritional
      state and some metabolic hormones in control of avian hypothalamic and ovarian
      ghrelin/ghrelin receptor system. We examined the effect of food restriction,
      administration of ghrelin 1-18, ghrelin antagonistic analogue (D-Lys-3)-GHRP-6,
      obestatin and combinations of them on the expression of ghrelin and ghrelin
      receptor (GHS-R1a) in hypothalamus and ovary of old (23months of age) and young
      (7months of age) chickens. Expression of mRNAs for ghrelin and GHS-R1a in both
      hypothalamus and largest ovarian follicle was measured by RT-PCR. It was observed
      that food restriction could promote the expression of ghrelin and GHS-R1a in
      hypothalamus and ovary of the old chickens, but in the young chickens it reduced
      expression of ghrelin and did not affect expression of GHS-R1a in the ovary.
      Administration of ghrelin 1-18 did not affect hypothalamic or ovarian ghrelin
      mRNA, but significantly increased the expression of GHS-R1a in hypothalamus, but
      not in ovary. (D-Lys-3)-GHRP-6, significantly stimulated accumulation of ghrelin,
      but not GHS-R1a mRNA in hypothalamus or ghrelin or GHS-R1a in the ovary. Ghrelin
      1-18 and (D-Lys-3)-GHRP-6, when given together, were able either to prevent or to
      induce effect of these hormones. Obestatin administration increased expression of
      ghrelin gene in the hypothalamus, but not expression of hypothalamic GHS-R1a,
      ovarian ghrelin and GHS-R1a. Furthermore, obestatin was able to modify effect of
      both ghrelin and fasting on hypothalamic and ovarian mRNA for ghrelin GHS-R1a.
      Our results (1) confirm the existence of ghrelin and its functional receptors GHS
      R1a in the chicken hypothalamus and ovary (2) confirm the age-dependent control
      of ovarian ghrelin by feeding, (3) demonstrate, that nutritional status can
      influence the expression of both ghrelin and GHS-R1a in hypothalamus and in the
      ovary (3) demonstrates for the first time, that ghrelin can promote generation of
      its functional receptor in the hypothalamus, but not in the ovary, (4) show that
      ghrelin1-18 and (D-Lys-3)-GHRP-6 could not only be antagonists in the action on
      chicken hypothalamus and ovaries, but also independent regulators and even
      agonists, and (5) provide first evidence for action of obestatin on hypothalamic
      ghrelin and on the response of hypothalamic and ovarian ghrelin/GHS-R1a system to
      food restriction. These data indicate the involvement of both hypothalamic and
      ovarian ghrelin/GHS-R1 systems in mediating the effects of nutritional status,
      ghrelin and obestatin on reproductive processes.

PMID- 22877786
TI  - 7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons
      in a rat model of Parkinson's disease.
AB  - Neuronal nitric oxide synthase (nNOS) is involved in the regulation of diverse
      intracellular messenger systems in the brain. Nitric Oxide (NO) contributes to
      inducing signaling cascades that involve a complex pattern of phosphorylation of
      DARPP-32 (in Thr-34), which controls the phosphoproteins involved in neuronal
      activation. However, the role of NO in the pathophysiology of Parkinson's disease
      (PD) and its effect in striatal neurons have been scarcely explored. In the
      present work, we investigate the effects of a nitric oxide synthase (NOS)
      inhibitor, 7-nitroindazole (7-NI) in the nigrostriatal pathway of striatal 6
      hydroxydopamine (6-OHDA) lesioned rats. Our quantitative histological findings
      show that treatment with 7-NI significantly reduced 6-OHDA-induced dopaminergic
      damage in the dorsolateral striatum and Substantia Nigra pars compacta (SNpc).
      Moreover, 6-OHDA lesioned rats show a significant increase of nNOS(+) and Phospho
      Thr34-DARPP-32(+) cells, accompanied by a consequent decrease of total DARPP
      32(+) cells, which suggests an imbalance of NO activity in the DA-depleted
      striatum, which is also reflected in behavioral studies. Importantly, these
      effects are reverted in the group treated with 7-NI. These results show a clear
      link between the state of phosphorylation of DARPP-32 and parkinsonism, which is
      regulated by nNOS. This new evidence suggests a prominent role for nitric oxide
      in the neurotransmitter balance within the basal ganglia in the pathophysiology
      of experimental parkinsonism.

PMID- 22877787
TI  - Posttraumatic stress in professional firefighters in Japan: rescue efforts after
      the Great East Japan Earthquake (Higashi Nihon Dai-Shinsai).
AB  - INTRODUCTION: Firefighters are often exposed to stressful duty-related events and
      may experience extreme trauma. Such work-related stress can result in
      posttraumatic stress disorder (PTSD). It is therefore important to understand the
      traumatic stress experienced by firefighters in the course of their work and to
      promote appropriate intervention when necessary. METHODS: Data were collected
      from 118 workers (all males) in the Fire Department of Akita City, Japan who had
      participated in the Great East Japan Earthquake (Higashi Nihon Dai-Shinsai)
      rescue effort from March 11 through March 31, 2011. Study participants completed
      self-report surveys at three time intervals: shortly after return from the rescue
      effort, approximately two weeks after return from the rescue effort, and
      approximately one month after return from the rescue effort. The surveys included
      questions of demographics, physical complaints, medical history, and the Impact
      of Event Scale-Revised (IES-R) Japanese version, in which a cut-off point of
      24/25 was set to screen for PTSD. RESULTS: A total of 117 participants undertook
      the initial survey with a range of 0-36 points obtained on the IES-R score. For
      the initial survey, two of 117 participants scored >=25 points. For the
      intermediate survey phase, a range of 0-19 was obtained for 116 participants and
      for the final survey phase, a range of 0-11 points was obtained for 114
      participants. CONCLUSION: Contrary to expectations, the survey results showed no
      participant was judged to require prompt consultation for PTSD. The firefighters
      who participated in this study were in good mental health. However, more detailed
      study is required to ascertain whether these findings adequately and clearly
      reflect the mental health status of these participants.

PMID- 22877788
TI  - A kick in the shins: the financial impact of uncontrolled warfarin use in pre
      tibial haematomas.
AB  - Warfarin is increasingly prescribed in the elderly population for a number of
      medical conditions. Pre-tibial haematomas are a common cause of morbidity in this
      group. The aim of the study was to identify the proficiency of INR monitoring at
      a primary care level in correlation with their recommended INR range and to study
      the treatment outcome in this group. A retrospective single-centre study of
      patients diagnosed with pre-tibial haematomas was conducted over a two-year
      period. Length of hospital stay, time delay until operative intervention, blood
      transfusion and warfarin reversal requirements, social care input and cost to the
      NHS were considered. A total of 62 patients were admitted with pre-tibial
      haematomas of which 20 were on Warfarin. Females were predominantly more affected
      (5.6:1). The mechanism of injury was as a result of minor trauma. The mean INR
      level was 3.8 with a standard deviation of 3.1. Mean length of hospital stay was
      11 days with a standard deviation of 13.6. Nine patients required skin grafting.
      Average cost for the acute episode was L3500 per patient. INR levels were
      significantly outwith the target range causing substantial patient morbidity and
      imposing a significant financial burden on the NHS. Tighter regulation at a
      primary care level should help reduce this risk. 

PMID- 22877789
TI  - Major incident triage: comparative validation using data from 7th July bombings.
AB  - INTRODUCTION: The importance of health service planning for major incident
      management has been recognised since the World Trade Centre attacks of September
      2001 and is highly relevant to planning for the 2012 Olympics. UK national Major
      Incident guidance stipulates the use of a system of triage for casualties to
      prioritise treatment and ensure "the greatest good for the greatest number".
      However, at least three triage systems are in use worldwide and no evidence
      exists to demonstrate their relative efficacy. The transport bombings in London
      on 7th July 2005 caused the largest number of casualties on mainland UK soil
      since World War 2. We aimed to validate three major incident triage systems using
      patient data from the 7th July bombings. PATIENTS AND METHODS: A retrospective
      cohort of patients from the 7th July bombings treated at the Royal London
      Hospital (RLH) was examined. Clinical information collected on arrival at RLH was
      used to allocate triage categories using the START, Manchester Sieve and
      CareFlight triage systems. The value of each system in identifying the critically
      injured patient was calculated. RESULTS: 203 sets of records were examined.
      Outcome data was available for 166 patients, of whom 8 were critically injured.
      Of these 166 patients, triage categories could be retrospectively allocated for
      124 (START), 127 (Manchester Sieve), 128 (CareFlight), including 4 of the
      critically injured. All three systems identified the same three patients as P1 or
      P2. The triage systems performed identically in identifying the critically
      injured, with sensitivity 50% and specificity 100% if using only the highest
      priority, or sensitivity 75% and specificity 99% if using the top 2 priority
      groups. Significant amounts of data were not recorded in prehospital and hospital
      notes. DISCUSSION AND CONCLUSIONS: Systematic triage of mass casualties is
      effective but the amount of missing data seriously compromises any attempt to
      evaluate systems of trauma care in a major incident.

PMID- 22877790
TI  - Benefit of Helicopter Emergency Medical Services on trauma patient mortality in
      the Netherlands?

PMID- 22877791
TI  - Spontaneously hypertensive rat as experimental model of salivary hypofunction.
AB  - OBJECTIVE: To analyse the salivary activity in spontaneously hypertensive rats
      (SHRs) evaluating biochemical parameters of saliva in 4-week-old and 12-week-old
      animals. DESIGN: Systolic blood pressure (SBP) was recorded by tail
      plethysmography. The salivary flow rate was stimulated by pilocarpine (SFR). The
      pH and salivary buffering capacity (SBC) were evaluated with a specific
      electrode. The concentrations of fluoride ([F(-)]) and calcium ([Ca(++)]) ions
      were determined using an electrode connected to a calibrated ion analyser. The
      total protein concentration was determined by Lowry method, and amylase activity
      by kinetic method. The salivary IgA was determined by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: The SFR, [F(-)] and [Ca(++)] increased with age in
      normotensive rats, however no alteration in pH, total protein and IgA was
      observed between 4 and 12 weeks old Wistar rats. SBC decreased with age in Wistar
      rats. The SFR was not altered between SHRs in different ages and it was lower in
      12 weeks old SHR when compared to Wistar rats. An increase in the protein
      concentration, and in the amylase activity and [F(-)] was observed with the
      development of SHR. Unaltered SBC, salivary IgA and [Ca(++)] were observed in 12
      weeks old when compared to 4 weeks old SHR. The [Ca(++)] ions were reduced in
      saliva of SHR than that of Wistar rats at 12 weeks. A lower pH was observed in
      saliva of Wistar than that of SHR at 12 weeks. CONCLUSIONS: SHR is an
      experimental model of salivary hypofunction, the decreased SFR observed in SHR at
      different ages was associated to salivary biochemical parameter alterations.

PMID- 22877792
TI  - Haplotypes of susceptibility to chronic periodontitis in the Interleukin 8 gene
      do not influence protein level in the gingival crevicular fluid.
AB  - OBJECTIVE: Previously, we identified that the ATC/TTC haplotype formed by
      polymorphisms in the Interleukin-(IL)8 gene conferred susceptibility to chronic
      periodontitis (CP). The aim of the study was to investigate whether the IL8
      haplotype ATC/TTC was associated with the volume of gingival crevicular fluid
      (GCF), the concentration of interleukin IL-8 in the GCF, as well as periodontal
      conditions in patients with CP in comparison to controls without CP. METHODS:
      Seventy-nine individuals (CP: n=41, controls: n=38) were grouped according to the
      presence (susceptible for CP) or absence (not susceptible for CP) of the IL8
      ATC/TTC haplotype. After periodontal clinical evaluation, they were subdivided by
      the presence or absence of CP. GCF was collected from each patient and the IL-8
      levels were determined by ELISA. The GCF volume of each subject was measured by
      means of a calibrated electronic device. Comparisons of means between carriers
      and non-carriers of the ATC/TTC haplotype were evaluated using the Mann-Whitney
      test. Linear regression and stepwise linear regression analysis were used to
      analyse the association of the GCF volume with potential covariates and their
      contribution for the phenotype. RESULTS: We did not find significant differences
      of both periodontal conditions and IL-8 concentration in the GCF of patients with
      the presence or absence of the IL8 ATC/TTC haplotype. However, the GCF volume was
      significantly higher amongst the patients affected by CP that are absent for the
      IL8 ATC/TTC haplotype. In addition, linear regression analysis showed a
      statistically significant association between GCF volume and CP, IL8 haplotype
      ATC/TTC and IL-8 concentration. CONCLUSIONS: The IL8 haplotype of susceptibility
      to CP was neither associated with IL-8 cytokine levels nor with clinical
      periodontal parameters. Also, CP, IL8 haplotype and IL-8 concentration showed a
      positive association with the GCF volume levels in the studied patients.

PMID- 22877793
TI  - Tooth-PDL-bone complex: response to compressive loads encountered during
      mastication - a review.
AB  - The components of the tooth-periodontal ligament (PDL)-alveolar bone complex act
      in a synergistic manner to dissipate the loads incurred during mastication. The
      complex incorporates a diverse array of structural features for this purpose.
      These include the non-mineralized and hence soft PDL that absorbs much of the
      initial loads. The internal structure of the tooth also includes soft interphases
      that essentially surround the dentine core. These interphases, although stiffer
      than the PDL, still are more compliant than the dentine core, and are thus key
      components that allow the tooth itself to deform and hence help dissipate the
      compressive loads. There is also direct evidence that even under moderate
      compressive loads, when the tooth moves in the alveolar bone socket, this
      movement is guided by specific locations where the tooth comes into contact with
      the bone surface. The combination of all these responses to load is that each
      tooth type appears to move and deform in a specific manner when loaded. Much,
      however, still remains to be learned about these three-dimensional responses to
      load and the factors that control them. Such an understanding will have major
      implications for dentistry, that include a better understanding of phenomena such
      as abfraction, the manner in which tooth implants function even in the absence of
      a PDL-like tissue and the implications to bone remodelling of the movements
      imposed during orthodontic interventions.

PMID- 22877794
TI  - Intraoperative enteroscopy in the management of obscure gastrointestinal
      bleeding.
AB  - Obscure gastrointestinal bleeding has long been a diagnostic challenge because of
      the relative inaccessibility of small bowel to standard endoscopic evaluation.
      Intraoperative enteroscopy indications have been reduced by the development of
      deep enteroscopy techniques and video capsule endoscopy. In light of the current
      advances, this review aimed at evaluating the intraoperative enteroscopy
      technical aspects, study results and an ongoing role for intraoperative
      enteroscopy in obscure gastrointestinal bleeding management. Intraoperative
      enteroscopy allows complete small bowel exploration in 57-100% of cases. A
      bleeding source can be identified in 80% of cases. Main causes are vascular
      lesions (61%) and benign ulcers (19%). When a lesion is found, intraoperative
      enteroscopy allows successful and recurrence-free management of gastrointestinal
      bleeding in 76% of cases. The reported mortality is 5% and morbidity is 17%. The
      recurrence of bleeding is observed in 13-52% of cases. With the recent
      development of deep enteroscopy techniques, intraoperative enteroscopy remains
      indicated when small bowel lesions (i) have been identified by a preoperative
      work-up, (ii) cannot be definitively managed by angiographic embolization,
      endoscopic treatment or when surgery is required and (iii) cannot be localized by
      external examination during surgical explorations. Surgeons and endoscopists must
      exercise caution with intraoperative enteroscopy to avoid the use of a low yield,
      highly morbid procedure.

PMID- 22877795
TI  - Cruciferous vegetables intake is inversely associated with risk of breast cancer:
      a meta-analysis.
AB  - PURPOSE: The objective of the study was to examine the associations of
      cruciferous vegetables intake with risk of breast cancer. METHODS: Studies were
      identified by searching PubMed databases and screening the references of
      retrieved articles and reviews. Summary odds ratios (ORs) for the highest versus
      lowest cruciferous vegetables consumption levels were calculated using fixed or
      random effects models depending on heterogeneity between studies. Heterogeneity
      among studies was examined using Q and I(2) statistics. Publication bias was
      assessed using the Egger's and Begg's tests. RESULTS: Thirteen epidemiologic
      studies (11 case-control and 2 cohort studies) were included in the meta
      analysis. The combined results from all studies indicated that high cruciferous
      vegetables intake was significantly associated with reduced breast cancer risk
      (RR = 0.85, 95% CI = 0.77-0.94). CONCLUSION: Findings from this meta-analysis
      suggest that cruciferous vegetables consumption may reduce the risk of breast
      cancer. Because of the limited number of studies, further prospective studies are
      needed to explore the protective effect of cruciferous vegetables on breast
      cancer.

PMID- 22877796
TI  - The trouble with ischemia.

PMID- 22877797
TI  - In search of the efficient way to medical decisions: the case of acute heart
      failure syndrome.

PMID- 22877798
TI  - Bayesian adaptive trial design in acute heart failure syndromes: moving beyond
      the mega trial.
AB  - Over the last 2 decades, early treatment for patients presenting with acute heart
      failure syndromes (AHFS) has changed very little. Despite strikingly different
      underlying disease pathophysiology, presenting signs and symptoms, and
      precipitants of AHFS, most patients are treated in a homogeneous manner with
      intravenous loop diuretics. Inhospital studies of new therapies have produced
      disappointingly neutral results at best. Patients continue to be enrolled in
      trials long after initial therapy, at a time when vital signs have improved,
      symptoms have changed, and initiating pathophysiologic processes, such as
      myocardial and renal injury, have already begun. The "one-size-fits-all" approach
      to inhospital AHFS trials have been recognized as one potential contributor to
      the disappointing trial results seen to date. Studies designed to tailor the
      therapeutic approach to ascertain which treatment modalities are most effective
      depending on patient phenotypes have not been previously conducted in AHFS
      because this objective is not traditional in clinical trial design. Utilizing
      Bayesian adaptive designs in trials of early AHFS provides an opportunity to
      personalize therapy within the constraints of clinical research. Bayesian
      adaptive design is increasingly recognized as an efficient method for obtaining
      valid clinical trial results. At its core, this approach uses existing
      information at the time of trial initiation, combined with data accumulating
      during the trial, to identify treatments most beneficial for specific patient
      subgroups. Based on accumulating evidence, the study then "adapts" its focus to
      critical differences between treatments within patient subgroups. Bayesian
      adaptive design is ideally suited for investigating complex, heterogeneous
      conditions such as AHFS and affords investigators the ability to study multiple
      treatment approaches and therapies in multiple patient phenotypes within a single
      trial, while maintaining a reasonable overall sample size. Identifying specific
      treatment approaches that safely improve symptoms and facilitate early discharge
      in patients who traditionally are admitted, often for prolonged periods of time,
      are necessary if we aim to reverse the disappointing trend in clinical trial
      results. In this study, AHFS clinical researchers and biostatisticians with
      expertise and experience in designing "personalized medicine" trials describe the
      development of a Bayesian adaptive design for an emergency department-based AHFS
      trial.

PMID- 22877799
TI  - The rationale and design of the Shockless IMPLant Evaluation (SIMPLE) trial: a
      randomized, controlled trial of defibrillation testing at the time of
      defibrillator implantation.
AB  - Defibrillation testing (DT) has been an integral part of defibrillator
      (implantable cardioverter defibrillator [ICD]) implantation; however, there is
      little evidence that it improves outcomes. Surveys show a trend toward ICD
      implantation without DT, which now exceeds 30% to 60% in some regions. Because
      there is no evidence to support dramatic shift in practice, a randomized trial is
      urgently needed. The SIMPLE trial will determine if ICD implantation without any
      DT is noninferior to implantation with DT. Patients will be eligible if they are
      receiving their first ICD using a Boston Scientific device (Boston Scientific,
      Natick, MA). Patients will be randomized to DT or no DT at the time of ICD
      implantation. In the DT arm, physicians will make all reasonable efforts to
      ensure 1 successful intraoperative defibrillation at 17 J or 2 at 21 J. The first
      clinical shock in all tachycardia zones will be set to 31 J for all patients. The
      primary outcome of SIMPLE will be the composite of ineffective appropriate shock
      or arrhythmic death. The safety outcome of SIMPLE will include a composite of
      potentially DT-related procedural complications within 30 days of ICD
      implantation. Several secondary outcomes will be evaluated, including all-cause
      mortality and heart failure hospitalization. Enrollment of 2,500 patients with
      3.5-year mean follow-up will provide sufficient statistical power to demonstrate
      noninferiority. The study is being performed at approximately 90 centers in
      Canada, Europe, Israel, and Asia Pacific with final results expected in 2013.

PMID- 22877800
TI  - Is there an association between aspirin dosing and cardiac and bleeding events
      after treatment of acute coronary syndrome? A systematic review of the
      literature.
AB  - BACKGROUND: Current acetylsalicylic acid (ASA) dosing algorithms for the
      prevention of secondary thrombotic events in acute coronary syndrome (ACS)
      patients are inconsistent and lack sufficient data support. METHODS: We performed
      a systematic review of the literature for studies that assessed clinical outcomes
      in patients with ACS following coronary stent insertion (SI) or medical treatment
      (MT). Acetylsalicylic acid dosing was stratified into low- (<160 mg) and high-
      (>= 160 mg) dose categories. Outcomes were assessed at 1, 6, and 12 months and
      included major bleeding, myocardial infarction, and all-cause death. A random
      effects meta-analysis was used to estimate the value of the mean for each outcome
      variable. RESULTS: Of 12,472 publications identified, 136 studies with 289,330
      patients were analyzed. In the 1-month SI analysis, proportions of patients (95%
      CI) in the low- and high-dose ASA categories experiencing major bleeding were
      2.1% (1.5-2.6) and 1.9% (0.0-3.8); proportions with myocardial infarction were
      2.1% (1.3-2.8) and 1.8% (0.9-2.6); and proportions of all-cause death were 2.8%
      (2.2-3.4) and 2.4% (1.3-3.5), respectively. Results were similar in the MT
      analysis, except that major bleeding rates for low and high doses were 1.7% (1.3
      2.2) and 4.0% (2.2-5.8), respectively. Regression analyses suggested that the
      proportion of patients reporting each of the outcomes evaluated were not
      significantly different between the low- and high-dose categories, with the
      exception of the 1-month major bleeding following MT. CONCLUSIONS: Our results
      suggest no improved clinical outcomes associated with higher ASA maintenance
      doses in ACS patients receiving SI or MT. In the MT analysis, there was more
      major bleeding in the first month after an ACS event with high-dose ASA.

PMID- 22877801
TI  - Anatomy, mechanics, and pathophysiology of the mitral annulus.
AB  - The mitral annulus plays an important role in leaflet coaptation, in unloading
      mitral valve closing forces, and in promoting left atrial and left ventricular
      filling and emptying. Perturbations of annular mechanics figure prominently in a
      number of disorders including functional and ischemic mitral regurgitation,
      mitral valve prolapse, atrial fibrillation, mitral annular calcification, and
      annular submitral aneurysm. This review discusses the role of annular dysfunction
      in the pathogenesis of these disorders.

PMID- 22877803
TI  - Under-reporting of cardiovascular events in the rofecoxib Alzheimer disease
      studies.
AB  - BACKGROUND: In September 2004, rofecoxib (Vioxx) was removed from the market
      after it was found to produce a near doubling of cardiovascular thrombotic (CVT)
      events in a placebo-controlled study. Its manufacturer stated that this was the
      first clear evidence of such risk and criticized previous analyses of earlier CVT
      risk for focusing on investigator-reported events. We studied contemporaneously
      adjudicated CVT events to assess the information on cardiovascular risk available
      while the drug was in widespread use. METHODS: Using an intention-to-treat
      analysis of adjudicated CVT deaths, we analyzed detailed patient-level data
      collected during 3 randomized placebo-controlled trials of rofecoxib versus
      placebo that had been designed to define the drug's possible role in the
      prevention or treatment of Alzheimer disease. All trials had been completed by
      April 2003. RESULTS: In the 3 studies combined, the data indicated that rofecoxib
      more than tripled the risk of confirmed CVT death (risk ratio = 3.57 [1.48-9.72],
      P = .004). This finding reached the P < .05 level of significance by June 2001.
      CONCLUSION: Intention-to-treat analysis of placebo-controlled studies of
      rofecoxib for Alzheimer disease demonstrated that the drug produced a significant
      increase in confirmed CVT deaths nearly 40 months before it was removed from the
      market. By contrast, published analyses of these trials were restricted to on
      treatment analyses (ending 14 days after cessation of treatment) that did not
      reveal this risk. Intention-to-treat analyses of clinical trial data can reveal
      important information about potential drug risks and should be performed
      routinely and reported in a timely manner.

PMID- 22877802
TI  - Porcine bioprosthetic heart valves: The next generation.
AB  - There have been significant advances in organ xenotransplantation (cross-species
      transplantation), especially in the development of genetically engineered pigs,
      but clinical trials of solid organ transplants are still a time away. However,
      there is a form of pig-to-human xenotransplantation that has been taking place
      since the 1960s-bioprosthetic heart valve (BHV) replacement. Recently, there has
      been increasing evidence that, despite glutaraldehyde fixation of BHVs, there is
      a significant immune reaction to the valves, leading to calcification, rapid
      structural deterioration, and failure, particularly in young patients who have a
      more vigorous immune system and metabolism than the elderly. However, it is the
      young patients who would most benefit from such BHVs because these avoid the
      complications associated with the lifelong anticoagulation required with
      mechanical valves. In this review, we examine pathologic and immunohistochemical
      reports of failed BHVs that suggest that there is an immune response to these
      valves. Small animal studies that link the development of calcification and BHV
      failure to the immune response are reviewed. We draw parallels between the
      problems of glutaraldehyde-fixed tissue xenotransplantation and those currently
      being faced in live organ xenotransplantation. Finally, we discuss the advances
      being made in the production of genetically modified pigs and the evidence that
      these pigs may become a source of BHVs that can be used worldwide to treat
      valvular heart disease in children and young adults (for whom there is no ideal
      valve replacement in existence today). The design of a BHV that is resistant to
      the host's immune response would be a major step forward in cardiac surgery.

PMID- 22877804
TI  - Usefulness of high-sensitivity troponin T for the evaluation of patients with
      acute chest pain and no or minimal myocardial damage.
AB  - BACKGROUND: Although high-sensitivity troponins allow early diagnosis of acute
      myocardial infarction, their role for identification of acute coronary syndrome
      in patients with normal conventional troponin remains unclear. METHODS AND
      RESULTS: A total of 446 patients presenting to the emergency department with
      chest pain and normal troponin (common practice assays) in 2 serial samples were
      included. Both samples were also centrally analyzed for high-sensitivity troponin
      T (hs-TnT) (Roche Diagnostics, Basel, Switzerland). Detection (>3 ng/L) and 99th
      percentile (>= 14 ng/L) cutoffs of the maximum hs-TnT levels (hs-TnTmax) were
      considered. The end points were acute coronary syndrome diagnosis and the
      composite of in-hospital revascularization or 30-day cardiac events. RESULTS:
      Acute coronary syndrome was adjudicated to 84 patients (19%), and 62 (14%) had
      the composite end point. In univariate setting, hs-TnTmax >3 ng/L exhibited high
      sensitivity (87% and 92%, respectively) and negative predictive value (93% and
      97%) for both end points, whereas hs-TnTmax >= 14 ng/L provided high specificity
      (90% and 89%), although low positive predictive values (40% and 33%). After
      adjusting for clinical (pain characteristics and risk factors) and
      electrocardiographic data, there was a stepped increase of risk across hs-TnTmax
      categories (<= 3, >3 but <14, and >= 14 ng/L) for both end points; however, the
      discriminative capacity added was marginal (integrated discrimination improvement
      of 2.6% and 3.5%, respectively). CONCLUSIONS: Clinical and electrocardiographic
      data remain the most important tools for the evaluation of patients with chest
      pain and with no or minimal myocardial damage. The main contribution of hs-TnT is
      the high negative predictive value of undetectable levels (<= 3 ng/L).

PMID- 22877805
TI  - Prehospital diagnosis and triage of ST-elevation myocardial infarction by
      paramedics without advanced care training.
AB  - BACKGROUND: Prehospital triage of ST-elevation myocardial infarction (STEMI) for
      primary percutaneous coronary intervention (PCI) reduces treatment times.
      Prehospital triage and transport of STEMI patients have traditionally been
      undertaken in emergency medical service systems with Advanced Care Paramedics
      (ACPs). However, ACPs are not available in many regions. A pilot study was
      conducted to determine the feasibility of prehospital STEMI triage in a region
      with only Primary Care Paramedics. METHODS: Hemodynamically stable patients with
      chest pain and suspected STEMI were brought directly to a catheterization
      laboratory for primary PCI. End points included accuracy of prehospital STEMI
      identification, complications during transfer, and treatment times. RESULTS: One
      hundred thirty-four consecutive patients with suspected STEMI were triaged for
      primary PCI. Only 1 patient developed complications during transport (rapid
      atrial flutter) that required ACP skills. One hundred thirty-three patients
      underwent urgent angiography, and 105 patients underwent PCI. Based on physician
      interpretation of the prehospital electrocardiogram, there was agreement with
      triage decision for 121 (90%) of the 134 cases. The final diagnosis based on the
      angiogram and cardiac markers was true STEMI for 106 patients and false positive
      for 28 patients. The median first medical contact to balloon time was 91 (81-115)
      minutes. CONCLUSIONS: Hemodynamically stable patients with suspected STEMI can be
      safely and effectively transported directly for primary PCI by paramedics without
      advanced care training. Prehospital STEMI triage for primary PCI can be extended
      to regions that have few or no paramedics with advanced care training.

PMID- 22877806
TI  - Evaluating the effectiveness of a rapidly adopted cardiovascular technology with
      administrative data: the case of drug-eluting stents for acute coronary
      syndromes.
AB  - BACKGROUND: Instrumental variable (IV) methods can correct for unmeasured
      confounding when using administrative (claims) data for cardiovascular outcomes
      research, but difficulties identifying valid IVs have limited their use. We
      evaluated the safety and efficacy of drug-eluting coronary stents (DES) compared
      with bare-metal stents (BMS) for Medicare beneficiaries with acute coronary
      syndromes using the rapid uptake of DES in clinical practice as an instrument. We
      compared results from IV with those from propensity score matching (PSM) and
      multivariable regression models. METHODS: This is a retrospective cohort study
      involving 62,309 fee-for-service beneficiaries 66 years and older treated with
      coronary stenting between May 2003 and February 2004. Outcomes were measured for
      46 months after revascularization using claims data. RESULTS: Recipients of DES
      were younger, had a lower prevalence of myocardial infarction, and had fewer
      comorbidities compared with BMS recipients. Use of DES was associated with lower
      rates of mortality by PSM (hazard ratio [HR] 0.80, CI 0.77-0.83) but not by IV
      (HR 0.99, CI 0.87-1.11). Instrumental variable models estimated a larger
      reduction in repeat revascularization (HR 0.76, CI 0.63-0.89) than did PSM (HR
      0.90, CI 0.87-0.93). CONCLUSIONS: Based on IV analysis, the increased utilization
      of DES relative to BMS among Medicare beneficiaries with acute coronary syndrome
      is associated with reduced rates of repeat revascularization and no difference in
      mortality. Instrumental variable approaches provide a useful complement to
      conventional approaches to cardiovascular outcomes research with administrative
      data.

PMID- 22877807
TI  - In-hospital mortality among patients with takotsubo cardiomyopathy: a study of
      the National Inpatient Sample 2008 to 2009.
AB  - BACKGROUND: Takotsubo cardiomyopathy is characterized by acute, reversible left
      ventricular apical ballooning. Little is known about the characteristics of
      patients with takotsubo cardiomyopathy who have in-hospital mortality. We sought
      to determine in-hospital mortality rate, complication rate, and characteristics
      of patients with in-hospital mortality related to takotsubo cardiomyopathy.
      METHODS: Patients diagnosed with takotsubo cardiomyopathy in the National
      Inpatient Database Samples 2008 to 2009 using International Classification of
      Diseases, Ninth Revision, code 42983 were included in this study. Our primary
      outcome was in-hospital mortality. In patients with takotsubo cardiomyopathy, we
      assessed demographic factors, the prevalence and associated mortality of
      underlying critical illnesses (acute ischemic stroke, sepsis, acute renal
      failure, respiratory insufficiency, and noncardiac surgery), and acute
      complications (acute congestive heart failure, respiratory insufficiency with
      congestive heart failure, cardiogenic shock, ventricular fibrillation/cardiac
      arrest, and intraaortic balloon pump placement). RESULTS: A total of 24,701
      patients with takotsubo cardiomyopathy were identified. In-hospital mortality
      rate was 4.2%. A total of 21,994 patients (89.0%) were female. Male patients had
      a higher mortality rate than females (8.4% vs 3.6%, P < .0001). Age and race were
      not associated with mortality. Of patients with in-hospital mortality, 81.4% had
      underlying critical illnesses. Male patients with takotsubo had higher incidence
      of underlying critical illnesses than their female counterparts (36.6% vs 26.8%,
      P < .0001). CONCLUSIONS: The presence of underlying critical illness was the main
      driver of mortality, as these patients comprised >80% of patients with in
      hospital mortality. Male patients, who were significantly more likely to have
      underlying critical illness, had significantly higher mortality rates than female
      patients. The presence of underlying critical illness likely explains the higher
      mortality rate among male patients.

PMID- 22877808
TI  - Prospective evaluation of the morbidity and mortality of wild-type and V122I
      mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis
      Cardiac Study (TRACS).
AB  - BACKGROUND: TRACS sought to describe the clinical outcomes and disease
      progression of transthyretin (TTR) cardiac amyloidosis (ATTR) in an observational
      study. Clinical course is largely determined by disease type with ATTR
      categorized as wild-type (ATTRwt) or genetic-variant protein (ATTRm). Prospective
      data are lacking in the most common TTR mutation, V122I, present in approximately
      3.5% of African Americans. METHODS: Patients with ATTRwt (n = 18) and V122I ATTRm
      (n = 11) were longitudinally assessed every 6 months for up to 2 years by
      functional class assessments, biochemical markers, and echocardiography. RESULTS:
      At baseline, no differences in clinical characteristics, biomarkers, or
      echocardiographic parameters were noted between patients with ATTRwt and patients
      with ATTRm. After 15.5 +/- 8 months, there were 11 deaths and 1 cardiac
      transplant, with higher mortality (73% vs 22%, P = .03) and cardiovascular
      hospitalization (64% vs 28%, P = .02) among patients with ATTRm. The median
      survival from diagnosis was 25.6 months for ATTRm vs 43.0 months for ATTRwt (P =
      .04). Univariate predictors of mortality included disease duration, heart rate >=
      70 beats/min, baseline stroke volume, left ventricular ejection fraction <50%,
      and ATTRm status. For each 6-month increment, the mean 6-minute walk distance
      declined by 25.8 m, N-terminal pro b-type natriuretic peptide increased by 1,816
      pg/mL, and left ventricular ejection fraction fell by 3.2%, for the entire
      cohort. CONCLUSIONS: In this prospective study, disease progression, morbidity,
      and mortality were observed in ATTR cardiomyopathy, particularly due to V122I,
      over a short duration. Given the prevalence of this mutation, further study of
      V122I in at-risk African American patients is warranted.

PMID- 22877809
TI  - Minimally clinically important difference in chronic breathlessness: every little
      helps.
AB  - OBJECTIVES: The aim of the study was to determine the minimally clinically
      important difference (MCID) for breathlessness due to chronic heart failure
      (CHF). BACKGROUND: The measurement of breathlessness is difficult because it is
      subjective and multifactorial. Statistically significant changes in assessment
      may not be clinically meaningful. This is the first determination of MCID in
      chronic breathlessness in CHF using patient-rated data. METHODS: Measurements
      were made as part of a randomized, controlled, crossover trial of morphine,
      oxycodone, or placebo for breathlessness in CHF. Breathlessness intensity was
      assessed at baseline and at the end of each intervention (day 4) using 11-point
      numerical rating scales (NRS), modified Borg (mBorg) scales, and global
      impression of change (GC) in breathlessness at day 4. From these data, the change
      in NRS or mBorg associated with a 1-point change in GC was calculated. RESULTS:
      Thirty-five patients completed all study interventions, resulting in 105 data
      sets. We defined MCID as a 1-point change in GC. Regression analysis found that
      the MCID, including 95% CIs, equaled change in average NRS breathlessness per 24
      hours of 0.5 to 2.0 U (P < .001), change in worst NRS breathlessness per 24 hours
      of 0.4 to 2.9 (P < .001), change in average mBorg score of 0.2 to 2.0 (P < .001),
      and change in worst mBorg score as between 0.3 and 1.9 (P < .001). Corresponding
      effect size calculations lay within the 95% CIs for the regression analysis for
      each measure. CONCLUSIONS: A 1-point change in NRS or mBorg score is a reasonable
      estimate of the MCID in average daily chronic breathlessness in CHF.

PMID- 22877810
TI  - Cigarette smoking exposure and heart failure risk in older adults: the Health,
      Aging, and Body Composition Study.
AB  - BACKGROUND: Although there is evidence linking smoking and heart failure (HF),
      the association between lifetime smoking exposure and HF in older adults and the
      strength of this association among current and past smokers is not well known.
      METHODS: We examined the association between smoking status, pack-years of
      exposure, and incident HF risk in 2,125 participants of the Health, Aging, and
      Body Composition Study (age 73.6 +/- 2.9 years, 69.7% women, 54.2% whites) using
      proportional hazard models. RESULTS: At inception, 54.8% of participants were
      nonsmokers, 34.8% were past smokers, and 10.4% were current smokers. During
      follow-up (median 9.4 years), HF incidence was 11.4 per 1,000 person-years in
      nonsmokers, 15.2 in past smokers (hazard ratio [HR] vs nonsmokers 1.33, 95% CI
      1.01-1.76, P = .045), and 21.9 in current smokers (HR 1.93, 95% CI 1.30-2.84, P =
      .001). After adjusting for HF risk factors, incident coronary events, and
      competing risk for death, a dose-effect association between pack-years of
      exposure and HF risk was observed (HR 1.09, 95% CI 1.05-1.14, P < .001 per 10
      pack-years). Heart failure risk was not modulated by pack-years of exposure in
      current smokers. In past smokers, HR for HF was 1.05 (95% CI 0.64-1.72) for 1 to
      11 pack-years, 1.23 (95% CI 0.82-1.83) for 12 to 35 pack-years, and 1.64 (95% CI
      1.11-2.42) for >35 pack-years of exposure in fully adjusted models (P < .001 for
      trend) compared with nonsmokers. CONCLUSIONS: In older adults, both current and
      past cigarette smoking increase HF risk. In current smokers, this risk is high
      irrespective of pack-years of exposure, whereas in past smokers, there was a dose
      effect association.

PMID- 22877811
TI  - Baseline stress myocardial perfusion imaging results and outcomes in patients
      with stable ischemic heart disease randomized to optimal medical therapy with or
      without percutaneous coronary intervention.
AB  - BACKGROUND: The COURAGE trial reported similar clinical outcomes for patients
      with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT)
      with or without percutaneous coronary intervention (PCI). The current post hoc
      substudy analysis examined the relationship between baseline stress myocardial
      ischemia and clinical outcomes based on randomized treatment assignment. METHODS:
      A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent
      baseline stress myocardial perfusion single-photon emission computed tomographic
      imaging. Site investigators interpreted the extent of ischemia by the number of
      ischemic segments using a 6-segment myocardial model. Patients were divided into
      those with no to mild (<3 ischemic segments) and moderate to severe ischemia (>=
      3 ischemic segments). Cox proportional hazards models were calculated to assess
      time to the primary end point of death or myocardial infarction. RESULTS: At
      baseline, moderate to severe ischemia occurred in more than one-quarter of
      patients (n = 468), and the incidence was comparable in both treatment groups (P
      = .36). The primary end point, death or myocardial infarction, was similar in the
      OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and
      moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65).
      There was no gradient increase in events for the overall cohort with the extent
      of ischemia. CONCLUSIONS: From the COURAGE trial post hoc substudy, the extent of
      site-defined ischemia did not predict adverse events and did not alter treatment
      effectiveness. Currently, evidence supports equipoise as to whether the extent
      and severity of ischemia impact on therapeutic effectiveness.

PMID- 22877812
TI  - High-sensitivity C-reactive protein as an independent predictor of progressive
      myocardial functional deterioration: the multiethnic study of atherosclerosis.
AB  - BACKGROUND: Systemic inflammation has been linked to the development of heart
      failure in population studies including Multi-Ethnic Study of Atherosclerosis
      (MESA), but little evidence exists regarding potential mechanism of this
      relationship. In this study, we used longitudinal magnetic resonance imaging
      follow-up analysis to examine whether C-reactive protein (CRP) levels relate to
      progressive myocardial functional deterioration as a potential mechanism of
      incident heart failure. METHODS: Regional myocardial functional data from MESA
      participants who had baseline CRP measurement and also underwent tagged cardiac
      magnetic resonance imaging both at baseline and at 5-year follow-up were
      analyzed. Left ventricular midwall and midslice peak circumferential strain
      (Ecc), of which a more negative value denotes stronger regional myocardial
      function, was measured. Circumferential strain change was calculated as the
      difference between baseline and follow-up Ecc. RESULTS: During the follow-up
      period, participants (n = 785) with elevated CRP experienced a decrease in
      strain, independent of age, gender, and ethnicity (B = 0.081, ?Ecc change per 1
      mg/L CRP change, 95% CI 0.036-0.126, P < .001, model 1) and, additionally, beyond
      systolic blood pressure, heart rate, diabetes, smoking status, body mass index,
      current medication, and glomerular filtration rate (B = 0.099, 0.052-0.145, P <
      .001, model 2). The relationship remained statistically significant after further
      adjustment for left ventricular mass, coronary calcium score, and interim
      clinical coronary events (B = 0.098, 0.049-0.147, P < .001, model 3). CONCLUSION:
      Higher CRP levels are related to progressive myocardial functional deterioration
      independent of subclinical atherosclerosis and clinical coronary events in
      asymptomatic individuals without previous history of heart disease.

PMID- 22877813
TI  - Underuse of cardiovascular preventive pharmacotherapy in patients presenting with
      ST-elevation myocardial infarction.
AB  - BACKGROUND: Multiple medications have proven efficacy for the primary prevention
      of coronary heart disease (CHD), but the appropriate patient population remains
      controversial. Even in the presence of multiple cardiovascular risk factors, many
      patients are not considered high risk and are not offered preventive medications
      despite proven efficacy. METHODS: We analyzed a prospective cohort of 1,710
      consecutive ST-elevation myocardial infarction (STEMI) patients treated in a
      regional STEMI system from May 2007 to July 2010 and enrolled in a comprehensive
      database that includes preadmission medications. RESULTS: Of the 1,707 patients
      analyzed, 1,180 (69.1%) did not have known CHD before their event; and 482
      (41.7%) of those patients had premature events (men <55 years old, women <65
      years old). In patients without known CHD, cardiovascular risk factors were
      abundant (52.1% had hypertension, 43.6% had dyslipidemia, 41.4% had a family
      history of CHD, 58.5% were current or former smokers, and 14.9% were diabetic).
      Despite the high prevalence of risk factors, only 24.1% were on aspirin, 16.1%
      were on a statin, and only 7.8% were taking an aspirin and statin. Use of
      preventive medications was even less common in patients with premature events,
      including aspirin (15.2% vs 30.2%, P value < .001), statins (11.1% vs 19.5%, P
      value < .001), and the combination (5.6% vs 9.4%, P value < .001). CONCLUSIONS:
      Approximately 70% of a contemporary STEMI population did not have known CHD
      before their event, and >40% of those events would be considered premature.
      Despite the significant burden of cardiovascular risk factors, use of preventive
      therapy was alarmingly low in patients presenting with STEMI.

PMID- 22877815
TI  - Proposed strategy for optimizing aldosterone blockade in heart failure.

PMID- 22877814
TI  - Randomized trial of lottery-based incentives to improve warfarin adherence.
AB  - BACKGROUND: Poor adherence to medications is a major cause of morbidity and
      inadequate drug effectiveness. Efforts to improve adherence have typically been
      either ineffective or too complex to implement in clinical practice. Lottery
      based incentive interventions could be a scalable approach to improving
      adherence. METHODS: This was a randomized, controlled clinical trial of a daily
      lottery-based incentive in patients on warfarin stratified by baseline
      international normalized ratio (INR). The trial randomized 100 patients to either
      a lottery-based incentive or no lottery intervention. Main outcome was out-of
      range INRs. RESULTS: Over 6 months, the overall percentage of out-of-range INRs
      did not differ between the 2 arms (mean 23.0% in lottery arm and 25.9% in control
      arm, adjusted odds ratio [OR] 0.93, 95% CI 0.62-1.41). However, among the a
      priori subgroup with a baseline INR below therapeutic range, there was a
      significant reduction in out-of-range INR in the lottery arm versus the control
      arm (adjusted OR 0.39, 95% CI 0.25-0.62), whereas there was no such effect among
      those with therapeutic INRs at baseline (adjusted OR 1.26, 95% CI, 0.76-2.09, P
      value for interaction = .0016). Among those with low INR at baseline, there was a
      nonsignificant 49% reduction in the odds of nonadherence with the intervention
      (OR 0.51, 95% CI 0.23-1.14). CONCLUSIONS: Although a lottery-based intervention
      was not associated with a significant improvement in anticoagulation control
      among all study participants, it improved control among an a priori group of
      patients at higher risk for poor adherence.

PMID- 22877817
TI  - Potential for food-drug interactions by dietary phenolic acids on human organic
      anion transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11).
AB  - Phenolic acids exert beneficial health effects such as anti-oxidant, anti
      carcinogenic, and anti-inflammatory activities and show systemic exposure after
      consumption of common fruits, vegetables, and beverages. However, knowledge
      regarding which components convey therapeutic benefits and the mechanism(s) by
      which they cross cell membranes is extremely limited. Therefore, we determined
      the inhibitory effects of nine food-derived phenolic acids, p-coumaric acid,
      ferulic acid, gallic acid, gentisic acid, 4-hydroxybenzoic acid, protocatechuic
      acid, sinapinic acid, syringic acid, and vanillic acid, on human organic anion
      transporter 1 (hOAT1), hOAT3, and hOAT4. In the present study, inhibition of OAT
      mediated transport of prototypical substrates (1 MUM) by phenolic acids (100 MUM)
      was examined in stably expressing cell lines. All compounds significantly
      inhibited hOAT3 transport, while just ferulic, gallic, protocatechuic, sinapinic,
      and vanillic acid significantly blocked hOAT1 activity. Only sinapinic acid
      inhibited hOAT4 (~35%). For compounds exhibiting inhibition > ~60%, known
      clinical plasma concentration levels and plasma protein binding in humans were
      examined to select compounds to evaluate further with dose-response curves
      (IC(50) values) and drug-drug interaction (DDI) index determinations. IC(50)
      values ranged from 1.24 to 18.08 MUM for hOAT1 and from 7.35 to 87.36 MUM for
      hOAT3. Maximum DDI indices for gallic and gentisic acid (?0.1) indicated a very
      strong potential for DDIs on hOAT1 and/or hOAT3. This study indicates that gallic
      acid from foods or supplements, or gentisic acid from salicylate-based drug
      metabolism, may significantly alter the pharmacokinetics (efficacy and toxicity)
      of concomitant therapeutics that are hOAT1 and/or hOAT3 substrates.

PMID- 22877818
TI  - Nanomechanical mapping of the osteochondral interface with contact resonance
      force microscopy and nanoindentation.
AB  - The bone-cartilage, or osteochondral, interface resists remarkably high shear
      stresses and rarely fails, yet its mechanical characteristics are largely
      unknown. A complete understanding of this hierarchical system requires mechanical
      property information at the length scales of both the interface and the
      connecting tissues. Here, we combined nanoindentation and atomic force microscopy
      (AFM) methods to investigate the multiscale mechanical properties across the
      osteochondral region. The nanoindentation modulus M ranged from that of the
      subchondral bone (M=22.8+/-1.8GPa) to that of hyaline articular cartilage
      embedded in PMMA (M=5.7+/-1.0GPa) across a narrow transition region <5MUm wide.
      Contact resonance force microscopy (CR-FM), which measures the frequency and
      quality factor of the AFM cantilever's vibrational resonance in contact mode, was
      used to determine the relative storage modulus and loss tangent of the
      osteochondral interface. With better spatial resolution than nanoindentation, CR
      FM measurements indicated an even narrower interface width of 2.3+/-1.2MUm.
      Furthermore, CR-FM revealed a 24% increase in the viscoelastic loss tangent from
      the articular calcified cartilage into the PMMA-embedded hyaline articular
      cartilage. Quantitative backscattered electron imaging provided complementary
      measurement of mineral content. Our results provide insight into the multiscale
      functionality of the osteochondral interface that will advance understanding of
      disease states such as osteoarthritis and aid in the development of biomimetic
      interfaces.

PMID- 22877819
TI  - Modulating rheological and degradation properties of temperature-responsive
      gelling systems composed of blends of PCLA-PEG-PCLA triblock copolymers and their
      fully hexanoyl-capped derivatives.
AB  - In this study, the ability to modulate rheological and degradation properties of
      temperature-responsive gelling systems composed of aqueous blends of poly(epsilon
      caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone-co
      lactide) (PCLA-PEG-PCLA) triblock copolymers (i.e. uncapped) and their fully
      capped derivatives was investigated. Uncapped and capped PCLA-PEG-PCLA triblock
      copolymers, abbreviated as degree of modification 0 and 2 (DM0 and DM2,
      respectively), were composed of identical PCLA and PEG blocks but different end
      groups: namely hydroxyl and hexanoyl end groups. DM0 was synthesized by ring
      opening polymerization of l-lactide and epsilon-caprolactone in toluene using PEG
      as initiator and tin(II) 2-ethylhexanoate as the catalyst. A portion of DM0 was
      subsequently reacted with an excess of hexanoyl chloride in solution to yield
      DM2. The cloud point and phase behaviour of DM0 and DM2 in buffer as well as that
      of their blends were determined by light scattering in a diluted state and by
      vial tilting and rheological measurements in a concentrated state.
      Degradation/dissolution properties of temperature-responsive gelling systems were
      studied in vitro at pH 7.4 and 37 degrees C. The cloud points of DM0/DM2 blends
      were ratio-dependent and could be tailored from 15 to 40 degrees C for blends
      containing 15 to 100wt.% DM0. Vial tilting and rheological experiments showed
      that, with solid contents between 20 and 30wt.%, DM0/DM2 blends (15/85 to
      25/75w/w) had a sol-to-gel transition temperature at 10-20 degrees C, whereas
      blends with less than 15wt.% DM0 formed gels below 4 degrees C and the ones with
      more than 25wt.% DM0 did not show a sol-to-gel transition up to 50 degrees C.
      Complete degradation of temperature-responsive gelling systems took ~100days,
      independent of the DM0 fraction and the initial solid content. Analysis of
      residual gels in time by GPC and (1)H-NMR showed no chemical polymer degradation,
      but indicated gel degradation by dissolution. Preferential dissolution of lactoyl
      rich polymers induced enrichment of the residual gels in caproyl-rich polymers.
      To the best of our knowledge, degradation of temperature-responsive gelling
      systems by dissolution has not been reported or hypothesized as being the
      consequence of acylation of polymers. In conclusion, blending of PCLA-PEG-PCLA
      triblock polymers composed of identical backbones but different end groups
      provides for a straightforward preparation of temperature-responsive gelling
      systems with well-characterized rheological properties and potential in drug
      delivery. Furthermore, acylation of triblock copolymers may allow for the design
      of bioerodible systems with control over degradation by polymer dissolution.

PMID- 22877820
TI  - Immunological impacts of oil sands-affected waters on rainbow trout evaluated
      using an in situ exposure.
AB  - Rainbow trout were exposed in situ to oil sands-affected waters for 21 d, either
      with or without an immune stimulation using inactivated Aeromonas salmonicida.
      Three aquatic systems were utilized for the experiment: a pond containing oil
      sands tailings capped with approximately 3 m of natural surface water, a second
      pond where unextracted oil sands materials were deposited in the watershed, and a
      reservoir receiving Athabasca River water as a reference caging location. The
      three systems showed a gradient of oil sands-related compounds, most notably,
      total naphthenic acids were highest in the system containing tailings (13 mg/L),
      followed by the system influenced by unextracted oil sands (4 mg/L), followed by
      the reference cage location (1 mg/L). Biochemical and chemical measures of
      exposure in rainbow trout showed the same trend, with the tailings-influenced
      system having the highest hepatic EROD activity and elevated bile fluorescence
      measured at phenanthrene wavelengths. Trout caged in the tailings-influenced
      location had significantly fewer leukocytes and smaller spleens as compared to
      the reference fish, though liver size and condition factor were unaffected. Fish
      in the tailings-influenced waters also demonstrated increased fin erosion,
      indicative of opportunistic infection. The trout exposed to tailing-influenced
      waters also showed a significantly decreased ability to produce antibodies to the
      inactivated A. salmonicida. Given the complexity of the exposure conditions,
      exact causative agents could not be determined, however, naphthenic acids,
      polycyclic aromatic hydrocarbons and pH correlate with the immunotoxic effects
      while elevated salinity or metals seem unlikely causes.

PMID- 22877821
TI  - A role for intracellular calcium downstream of G-protein signaling in
      undifferentiated human embryonic stem cell culture.
AB  - Multiple signalling pathways maintain human embryonic stem cells (hESC) in an
      undifferentiated state. Here we sought to define the significance of G protein
      signal transduction in the preservation of this state distinct from other
      cellular processes. Continuous treatment with drugs targeting G(alphas)-, G(alpha
      i/o)- and G(alpha-q/11)-subunit signalling mediators were assessed in independent
      hESC lines after 7days to discern effects on normalised alkaline phosphatase
      positive colony frequency vs total cell content. This identified PLCbeta,
      intracellular free calcium and CAMKII kinase activity downstream of G(alpha-q/11)
      as of particular importance to the former. To confirm the significance of this
      finding we generated an agonist-responsive hESC line transgenic for a G(alpha
      q/11) subunit-coupled receptor and demonstrated that an undifferentiated state
      could be promoted in the presence of an agonist without exogenously supplied bFGF
      and that this correlated with elevated intracellular calcium. Similarly,
      treatment of unmodified hESCs with a range of intracellular free calcium
      modulating drugs in biologically defined mTESR culture system lacking exogenous
      bFGF promoted an hESC phenotype after 1week of continuous culture as defined by
      co-expression of OCT4 and NANOG. At least one of these drugs, lysophosphatidic
      acid significantly elevates phosphorylation of calmodulin and STAT3 in this
      culture system (p<0.05). These findings substantiate a role for G-protein and
      calcium signalling in undifferentiated hESC culture.

PMID- 22877822
TI  - A fluorescent screening platform for the rapid evaluation of chemicals in
      cellular reprogramming.
AB  - Current strategies to monitor reprogramming into induced pluripotent stem cells
      (iPSCs) are limited in that they rely on the recognition of advanced stage
      biomarkers or they involve the transduction of genetically-modified cells. These
      limitations are particularly problematic in high-throughput screenings where cell
      availability, low cost and a rapid experimental protocol are critical issues.
      Herein we report the application of a pluripotent stem cell fluorescent probe
      (i.e. CDy1) as a reporter for the rapid screening of chemicals in reprogramming
      iPSCs. CDy1 stains early-stage iPSCs at 7dpi as well as matured iPSCs; hence it
      can partially overcome the slow kinetics of the reprogramming process. As a proof
      of concept, we employed a CDy1-based screening in 384 well-plates to examine the
      effect of newly synthesized hydroxamic acid derivatives in reprogramming mouse
      fibroblasts transduced with Oct4, Sox2 and Klf-4 without c-Myc. One compound (1
      26) was identified as a reprogramming enhancer by 2.5-fold and we confirmed that
      1-26 behaves as a histone deacetylase (HDAC) inhibitor. The successful
      identification of novel small molecules enhancing the generation of iPSCs by
      means of a rapid and simple protocol demonstrates the suitability of this CDy1
      based screening platform for the large scale and high-throughput evaluation of
      iPSC modulators.

PMID- 22877823
TI  - High-throughput karyotyping of human pluripotent stem cells.
AB  - Genomic integrity of human pluripotent stem cell (hPSC) lines requires routine
      monitoring. We report here that novel karyotyping assay, utilizing bead-bound
      bacterial artificial chromosome probes, provides a fast and easy tool for
      detection of chromosomal abnormalities in hPSC lines. The analysis can be
      performed from low amounts of DNA isolated from whole cell pools with simple data
      analysis interface. The method enables routine screening of stem cell lines in a
      cost-efficient high-throughput manner.

PMID- 22877825
TI  - Enterocytozoon bieneusi and Encephalitozoon cuniculi in horses kept under
      different management systems in the Czech Republic.
AB  - Faecal samples were collected from 377 horses on 23 farms with varying management
      systems in the Czech Republic. Microsporidia were found on 16 farms and the
      overall prevalence of Enterocytozoon bieneusi and Encephalitozoon cuniculi was
      17.3% (66/377) and 6.9% (26/377), respectively. The prevalence of E. cuniculi in
      horses over 3 years of age was significantly higher (10.0%) compared to younger
      horses (4.0%). No significant differences in prevalence were observed among
      stallions, geldings, and mares for both microsporidia. Significantly higher
      infection rates of E. bieneusi and E. cuniculi were recorded in horses kept in
      stables than those on pasture. Two genotypes of E. cuniculi (I and II) and 15
      genotypes of E. bieneusi including six previously described and nine novel
      genotypes were detected. The most common genotype detected was E. bieneusi
      genotype D identified in 51.5% (34/66) of positive horses. The identification of
      E. bieneusi genotypes D, EpbA, G and WL15, which were previously reported in
      pigs, humans, raccoons and horses, indicates that horses could be a potential
      source of zoonotic infection in humans.

PMID- 22877826
TI  - Distribution of, and risk factors associated with, sheep carcass condemnations
      due to Cysticercus ovis infection on Canadian sheep farms.
AB  - Cysticercus ovis, the intermediate stage of a canine tapeworm, Taenia ovis,
      produces cystic lesions in the skeletal and cardiac muscle of sheep which, if
      numerous, will result in the condemnation of an entire carcass. In 2007 and 2008,
      the number of carcass condemnations due to C. ovis rose dramatically across
      Canada, suggesting that the prevalence of this infection on sheep farms was
      increasing. Trace-back of 237 carcasses condemned at Ontario provincially
      inspected abattoirs, between March 2009 and March 2011, revealed they originated
      from 133 farms across Canada. A case-control study was performed (n=40 cases, 56
      controls) to identify farm-level risk factors associated with carcass
      condemnations due to C. ovis. Participating farms, located in Alberta,
      Saskatchewan, Manitoba and Ontario, were asked to answer a short questionnaire
      which collected information about each farm's geographic location and management
      practices. A multivariable logistic regression model revealed that farm dogs
      scavenging deadstock (OR=4.04; 95% CI: 1.16-14.04) and failing to dispose of
      deadstock (OR=11.78; 95% CI: 2.93-47.40) were significantly associated with
      condemnations (p <= 0.05).

PMID- 22877824
TI  - Cross-national differences in the prevalence and correlates of burden among older
      family caregivers in the World Health Organization World Mental Health (WMH)
      Surveys.
AB  - BACKGROUND: Current trends in population aging affect both recipients and
      providers of informal family caregiving, as the pool of family caregivers is
      shrinking while demand is increasing. Epidemiological research has not yet
      examined the implications of these trends for burdens experienced by aging family
      caregivers. Method Cross-sectional community surveys in 20 countries asked 13 892
      respondents aged 50+ years about the objective (time, financial) and subjective
      (distress, embarrassment) burdens they experience in providing care to first
      degree relatives with 12 broadly defined serious physical and mental conditions.
      Differential burden was examined by country income category, kinship status and
      type of condition. RESULTS: Among the 26.9-42.5% respondents in high-, upper
      middle-, and low-/lower-middle-income countries reporting serious relative health
      conditions, 35.7-42.5% reported burden. Of those, 25.2-29.0% spent time and 13.5
      19.4% money, while 24.4-30.6% felt distress and 6.4-21.7% embarrassment. Mean
      caregiving hours per week in those giving any time were 16.6-23.6 (169.9-205.8
      h/week per 100 people aged 50+ years). Burden in low-/lower-middle-income
      countries was 2- to 3-fold higher than in higher-income countries, with any
      financial burden averaging 14.3% of median family income in high-, 17.7% in upper
      middle-, and 39.8% in low-/lower-middle-income countries. Higher burden was
      reported by women than men and for conditions of spouses and children than
      parents or siblings. CONCLUSIONS: Uncompensated family caregiving is an important
      societal asset that offsets rising formal healthcare costs. However, the
      substantial burdens experienced by aging caregivers across multiple family health
      conditions and geographic regions threaten the continued integrity of their
      caregiving capacity. Initiatives supporting older family caregivers are
      consequently needed, especially in low-/lower-middle-income countries.

PMID- 22877827
TI  - Development of a modified molecular diagnostic procedure for the identification
      and quantification of naturally occurring strongylid larvae on pastures.
AB  - A molecular procedure was developed to detect and quantify larvae of different
      strongylid parasite species recovered from pasture samples. Two lamb flocks (L
      and S) grazed separate paddocks with different natural larvae challenges (one low
      [Paddock L] and one high [Paddock S] challenge) on a commercial farm in Western
      Australia. Pasture samples were collected and analysed for larvae on 9 separate
      occasions from each paddock. Pregnant Merino ewes were sampled on 3 separate
      occasions (2 pre-partum and 1 post-partum). Following lambing, 203 female
      crossbred lambs were identified, from which faecal samples were collected across
      five separate samplings. Lamb production and faecal attributes were recorded.
      Genomic DNA was extracted directly from lamb faeces, in addition to the genomic
      DNA extracts from strongylid larval species recovered from pastures. Faecal worm
      egg counts (FWECs) were undertaken. Species-specific qPCRs and conventional PCRs
      (ITS-2 nuclear ribosomal DNA) were used to screen samples for strongylid species
      (Teladorsagia circumcincta, Trichostrongylus spp., Haemonchus contortus,
      Chabertia ovina and Oesophagostomum venulosum). Negative correlations (r(2)>0.91)
      were found between qPCR C(q) values and log-transformed pasture larval counts for
      Trichostrongylus spp. and T. circumcincta. Moderate levels of agreement between
      pasture larval counts and qPCR results were observed (67%). A clear difference in
      pasture larval challenge levels was observed between the two flocks using both
      qPCR and conventional pasture larval counts. It is difficult to draw conclusions
      on the production performances of lambs from the two experimental flocks, as no
      further replicates were able to be conducted following this experiment. Flock L
      had higher dressing percentages than Flock S (P=0.038), along with significantly
      higher faecal consistency and breech fleece faecal soiling scores at successive
      samplings. The molecular procedures utilised in this study have the potential to
      be beneficial for livestock grazing management strategies and parasite
      surveillance, however further investigation is necessary before they can become
      part of routine diagnostics.

PMID- 22877828
TI  - Real-time PCR evaluation of Strongylus vulgaris in horses on farms in Denmark and
      Central Kentucky.
AB  - Strongyle parasites are ubiquitous in grazing horses, and the large strongyle
      Strongylus vulgaris is considered the most pathogenic helminth parasite of
      horses. Recent investigations have suggested an association between occurrence of
      this parasite and usage of selective therapy based on regular fecal egg counts.
      The established diagnostic method for S. vulgaris involves larval culture and
      subsequent morphological identification of third stage larvae under the
      microscope. Recently, a real-time PCR assay was developed and validated for the
      detection and semi-quantification of S. vulgaris eggs in equine fecal samples.
      The purposes of the present study were (a) to determine the presence of S.
      vulgaris by real-time PCR in Danish and American horses on farms using vastly
      different anthelmintic treatment regimens and (b) to evaluate the association
      between larval culture results and the PCR. A total of 991 horses representing 53
      different horse farms in Denmark and Central Kentucky were studied. Fresh fecal
      samples were collected from all horses, and strongyle eggs retrieved for DNA
      extraction and subsequent real-time PCR analysis. Individual larval cultures were
      performed on the Danish part of the data set (663 horses on 42 farms). On the
      Danish farms, the S. vulgaris PCR prevalence was found to be 9.2% on farms not
      basing parasite control on fecal egg counts, and 14.1% on farms using selective
      therapy. No horses were PCR positive in the American part of the study (328
      horses on 11 farms). Kappa-values indicated a moderate agreement between PCR and
      larval culture results, while McNemar tests revealed no statistical difference
      between the paired proportions. Significant associations were found between PCR
      cycle of threshold (Ct) value groups and larval culture counts. Results indicate
      that both diagnostic methods can be useful for determining the occurrence of S.
      vulgaris on horse farms, but that they both are affected by potential sources of
      error. The PCR results confirmed previous findings suggesting that S. vulgaris
      can reemerge under selective therapy regimens.

PMID- 22877829
TI  - Increasing patient centredness in outpatient care through closer collaboration
      with patient groups?: an exploratory study on the views of health care
      professionals working in quality management for office-based physicians in
      Germany.
AB  - OBJECTIVES: In Germany, "self-help friendliness" is an upcoming popular concept
      for the promotion of patient centredness through closer cooperation of health
      care services with self-help groups of chronically ill and/or disabled patients
      and their relatives. The study aimed at gathering information from physicians
      with special expertise in quality management on opportunities for and barriers
      against introducing more collaboration between physicians and self-help groups in
      outpatient care. METHODS: A cross-sectional explorative survey was conducted with
      quality circle moderators (group leaders) from four German federal states in 2008
      and 2010 (n=624 or 32.1% respondents out of 1943). Main outcome measure was the
      moderators' assessment of their peers, measured with 18 items. Statistical
      analyses were mainly descriptive, supplemented by subgroup analyses by federal
      state and characteristics of the respondents. RESULTS: Moderators see a large
      willingness of outpatient physicians to integrate self-help activities, and many
      opportunities for better cooperation with patient groups. Nevertheless, most
      types of cooperation need activation and motivation. To enhance the cooperation,
      additional fees by health insurance funds, CME credit points and the decrease of
      doctors' work load are most likely to be effective. CONCLUSIONS: Given the
      willingness of office-based physicians to cooperate with patient groups,
      increased patient centredness through cooperation seems to be an achievable
      quality target in medical practices in Germany. Self-help-friendliness in medical
      practices is considered as an important partnership approach; however, the
      implementation is still in the early stages and has to overcome diverse barriers,
      mainly based on unfavourable opinions, negative attitudes and lack of incentives.

PMID- 22877830
TI  - Preferences for support services among adolescents and young adults with cancer
      or a blood disorder: a discrete choice experiment.
AB  - BACKGROUND: Life-threatening illnesses in young people are traumatic for patients
      and their families. Support services can help patients and families deal with
      various non-medical impacts of diagnosis, disease and treatment. The aim of this
      study was to determine which types of support are most valued by adolescents and
      young adults (AYA) with cancer or blood disorders and their families. METHOD: A
      discrete choice experiment (DCE). Separate experiments were conducted with AYA
      and their carers. RESULTS: Completed surveys were returned by 83 patients and 78
      carers. AYA preferred emotional support for themselves (either by counsellors
      and/or peers), emotional support for their family, financial support and
      assistance returning to school/work over services relating to cultural and
      spiritual needs. Covariate analysis indicated female AYA were more likely than
      males to prefer emotional support, while males were more likely to prefer
      assistance returning to work/school. Carers preferred emotional support for their
      AYA and assistance returning to school/work. Like AYA, they were indifferent
      about services relating to cultural and spiritual needs. CONCLUSION: Providing
      the types of support services that people prefer should maximise effectiveness.
      This study suggests that AYA patients require support services that included
      financial aid, assistance returning to work/study, emotional support for
      themselves and for their family.

PMID- 22877831
TI  - Altered muscle recruitment during extension from trunk flexion in low back pain
      developers.
AB  - BACKGROUND: A functionally induced, transient low back pain model consisting of
      exposure to prolonged standing has been used to elucidate baseline neuromuscular
      differences between previously asymptomatic individuals classified as pain
      developers and non-pain developers based on their pain response during a standing
      exposure. Previous findings have included differences in frontal plane
      lumbopelvic control and altered movement strategies that are present prior to
      pain development. Control strategies during sagittal plane movement have not been
      previously investigated in this sample. The purpose of this research was to
      investigate neuromuscular control differences during the extension phase from
      trunk flexion between pain developers and non-pain developers. METHODS:
      Continuous electromyography and kinematic data were collected during standing
      trunk flexion and extension on 43 participants (22 male) with an age range of 18
      33 years, prior to entering into the prolonged standing exposure. Participants
      were classified as pain developer/non-pain developer by their pain response (>=
      10 mm increase on a 100 mm visual analog scale) during standing. Relative timing
      and sequencing data between muscle pairs were calculated through cross
      correlation analyses, and evaluated by group and gender. FINDINGS: Pain
      developers demonstrated a 'top-down' muscle recruitment strategy with lumbar
      extensors activated prior to gluteus maximus, while non-pain developers
      demonstrated a typical 'bottom-up' muscle recruitment strategy with gluteus
      maximus activated prior to lumbar extensors. INTERPRETATION: Individuals
      predisposed to low back pain development during standing exhibited altered
      neuromuscular strategies prior to pain development. These findings may help to
      characterize biomechanical movement profiles that could be important for early
      identification of people at risk for low back pain.

PMID- 22877832
TI  - The contribution of load magnitude and number of load cycles to cumulative low
      back load estimations: a study based on in-vitro compression data.
AB  - BACKGROUND: Cumulative low-back load is suggested to be associated with low back
      pain, possibly due to (micro-)fractures of spinal segments. Based on available in
      vitro data it can be assumed that, in order to predict spine segment failure from
      cumulative compressive loading, load magnitude should be weighted with an
      exponent higher than one, whereas the number of cycles should be weighted with an
      exponent lower than 1. The aim of the present study was to assess both exponents
      based on available in-vitro data. METHODS: Data on loading to fatigue fracture of
      spinal segments under cyclic compression in-vitro were used and converted to
      survival probability for 5 load levels and 5 levels of number of cycles. Three
      optimization procedures were used to estimate the exponent of load magnitude and
      load cycles separately, and load magnitude and load cycles combined. Goodness of
      fit was assessed by comparing the Akaike's Information Criterion (AIC) between
      models. FINDINGS: The best fit, based on AIC and average error per data point was
      obtained with weighting of load magnitude and number of load cycles with
      exponents of approximately 2.0 and 0.2, respectively. INTERPRETATION: The results
      show that a combination of load magnitude and number of load cycles weighted with
      exponents of approximately 2 and 0.2 respectively provides a suitable measure of
      cumulative spinal compression loading. This finding may be of relevance for
      assessing cumulative low-back loads in studies on the etiology of low-back pain.

PMID- 22877833
TI  - Emotion and behavior: a general factor of personality from the EAS Temperament
      Survey and the Strengths and Difficulties Questionnaire.
AB  - The mothers of 603 pairs of 3- to 13-year-old twins in Korea completed the
      Emotionality, Activity, Sociability (EAS) Temperament Survey and the Strengths
      and Difficulties Questionnaire in reference to their twins. Principal factor
      analysis of the seven scales comprising these measures yielded a general factor
      on which all the scales had moderate to large loadings. Univariate behavioral
      genetic analyses showed that individual differences on this general factor could
      best be accounted for by additive genetic and non-shared environmental effects,
      with a heritability of 53%. The results strengthen the construct validity of the
      general factor of personality (GFP) by extracting this higher-order dimension
      from disparate measures, and have implications regarding social desirability
      criticisms applied to the GFP theory.

PMID- 22877834
TI  - Intraosseous access in the prehospital setting: literature review.
AB  - BACKGROUND: Although the majority of Australian intensive care paramedics use the
      manual intraosseous infusion technique (MAN-IO), several other semiautomatic
      devices now are available, such as the bone injection gun (BIG) and the
      semiautomatic intraosseous infusion system (EZ-IO). Given the choice of devices
      now available, questions have been raised regarding success rates, accuracy,
      decay of skills, and adverse events. OBJECTIVES: Review the literature regarding
      the use of intraosseous (IO) devices in the prehospital setting. METHODS:
      Selected electronic databases (Medline, Embase, and CINAHL) were searched, and a
      hand search was conducted for grey-literature that included studies from the
      commencement of the process to the end of May 2010. Inclusion criteria were any
      study reporting intraosseous insertion and/or infusion (adult and pediatric) by
      paramedics in the prehospital setting. FINDINGS: The search located 2,100
      articles; 20 articles met the inclusion criteria. The review also noted that use
      of IO access (regardless of technique) offers a safe and simple method for
      gaining access to the patients' vascular system. A number of studies found that
      the use of semiautomatic devices offers better and faster intraosseous access
      compared with the use of manual devices, and also were associated with fewer
      complications. The findings also suggest that the use of semiautomatic devices
      can reduce insertion times and the number of insertion attempts when contrasted
      with the use of manual insertion techniques. Despite these findings,
      statistically no specific IO device has proven clinical superiority. CONCLUSION:
      While manual IO techniques currently are used by the majority of Australian
      paramedics, the currently available evidence suggests that semiautomatic devices
      are more effective. Further research, including cost-benefit analyses, is
      required at a national level to examine skill acquisition, adverse effects, and
      whether comparative devices offer clinically significant advantages.

PMID- 22877835
TI  - Divided attention of adolescents related to lifestyles and academic and family
      conditions.
AB  - BACKGROUND: Development of the ability to divide attention is of crucial
      importance in the transitional period from elementary to junior high school. The
      relationship between divided attention and the prevalence of fatigue or low
      academic motivation is observed in junior high school students. In order to
      clarify the factors underlying decreased ability to divide attention, we examined
      the relationships between divided attention, as assessed by the kana pick-out
      test, lifestyle factors, and academic and family conditions in junior high school
      students. METHODS: The study group consisted of 158 healthy 1st-, 2nd-, and 3rd
      grade level junior high school students. Each participant performed the kana pick
      out test and questionnaires dealing with lifestyle factors (nocturnal sleeping
      hours on school days, breakfast, exercise, watching television, and spending time
      with family members), and academic and family conditions (good friendships at
      school and praise from family members when participants showed good academic
      performance). RESULTS: On multiple regression analyses adjusted for grade and
      gender, scores on the kana pick-out test were positively associated with spending
      time with family members. In addition, the comprehension score of the kana pick
      out test was positively associated with having breakfast every day and praise by
      family members. The score was negatively associated with watching television.
      CONCLUSION: The present findings suggest that the ability to divide attention is
      independently associated with good lifestyles and academic and family conditions
      in junior high school students.

PMID- 22877836
TI  - MECP2 duplication syndrome in both genders.
AB  - BACKGROUND: Duplications involving the methyl-CpG-binding protein 2 gene (MECP2)
      locus at Xq28 have been frequently identified in male patients who exhibit a
      phenotype unique from that of Rett syndrome, which is mainly characterized by
      severe mental retardation, recurrent infections, and epilepsy. This combination
      of features is recognized as MECP2 duplication syndrome. METHODS: Genomic copy
      number was investigated for patients with unexplained mental retardation, and
      phenotypic features of the patients having interstitial duplications including
      MECP2 were analyzed. RESULTS: Three male and one female patients with MECP2
      duplication were identified. The phenotypic features of all the four patients
      were compatible with MECP2 duplication syndrome. The X-chromosome inactivation
      (XCI) pattern was analyzed in the female patient, identifying a skewed XCI that
      activated the X-chromosome containing the MECP2 duplication. Her mother possessed
      the same MECP2 duplication and a random XCI pattern but exhibited no phenotypic
      features, indicating a nonsymptomatic carrier. The brain magnetic resonance
      imaging revealed periventricular cystic lesions in all four patients, including
      the female patient. CONCLUSION: This study suggested clinical implications of the
      MECP2 duplication syndrome not only in the male but also in female patients with
      unexplained mental retardation.

PMID- 22877837
TI  - Stillbirth in cases of severe acute maternal morbidity.
AB  - OBJECTIVE: To determine the incidence and correlates of stillbirths among women
      with severe acute maternal morbidity (SAMM). METHODS: In an observational study
      of 728 women who had SAMM between January 2007 and December 2010 at a referral
      tertiary health facility in Benin, Nigeria, the incidence of stillbirth, and the
      clinical and demographic correlates of stillbirth were evaluated. RESULTS: The
      rate of stillbirth among women with SAMM was 210 per 1000 deliveries. The rate
      among women who had uterine rupture (643 per 1000 deliveries) far exceeded other
      cause-specific rates of stillbirth. Unbooked status (odds ratio [OR], 2.2; 95%
      confidence interval [CI], 1.3-3.8), low maternal education (OR, 2.1; 95% CI, 1.2
      4.0), vaginal delivery (OR, 8.1; 95% CI, 5.1-13.0), and maternal comorbidity (OR,
      12.9; 95% CI, 6.2-26.9) were factors associated with stillbirth after adjusting
      for confounding variables. CONCLUSION: In Nigeria, SAMM was found to be
      associated with an unacceptably high rate of stillbirth. Strategies to improve
      fetal surveillance among women with SAMM are necessary to address the excessively
      high incidence of stillbirth among these patients.

PMID- 22877838
TI  - Comparison of methotrexate, actinomycin D, and etoposide for treating low-risk
      gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To compare the efficacy and toxicity of 3 single agent
      chemotherapeutic regimens in low-risk gestational trophoblastic neoplasia
      (LRGTN). METHODS: A prospective study was conducted at a referral center in Rio
      de Janeiro, Brazil. Patients presenting with metastatic or non-metastatic LRGTN
      (risk score <= 6) in non-probabilistic sampling were assigned to 1 of 3
      treatments: methotrexate with folinic acid rescue (MTX-CF; n=20); actinomycin D
      (n=20); and etoposide (n=20). Women with less than 1 year of disease-free follow
      up after the first normal human chorionic gonadotropin (hCG) value were excluded.
      Outcome measures included primary remission rate; resistance to primary and
      sequential chemotherapy; period between treatment initiation and remission (hCG
      response); and prevalence of toxic effects. RESULTS: Primary remission was
      achieved by 48 patients (80.0%). The remission rate with etoposide was 100.0%,
      while the rates with actinomycin D and MTX-CF were 90.0% and 50.0%, respectively.
      Efficacy of etoposide was significantly greater than the other 2 agents
      (P<0.001). Alopecia was the most frequent adverse effect caused by etoposide.
      Common to all protocols were stomatitis, nausea, and vomiting. Mean time
      intervals between beginning treatment and remission were similar and all 60
      participants survived. CONCLUSION: Etoposide was the most effective regimen for
      treating metastatic and non-metastatic LRGTN.

PMID- 22877839
TI  - Clinic-level introduction of medical abortion in Vietnam.
AB  - OBJECTIVE: To assess the efficacy of medical abortion and patient satisfaction in
      the clinic setting, in addition to determining healthcare providers' views.
      METHODS: From 2006 to 2008, 2400 women were enrolled at 10 Vietnam Family
      Planning Association (VINAFPA) clinics in an operations research project.
      Participants took 200mg of oral mifepristone in the clinic and 400 MUg of oral
      misoprostol 2 days later at home or in the clinic. Abortion status was assessed
      at follow-up. Furthermore, in 2006, 900 clinicians at 45 health facilities
      answered a knowledge, attitudes, and practices survey to capture providers'
      views. RESULTS: In total, 93.8% of participants had successful medical abortions.
      The majority (84.5%) administered misoprostol at home. Adverse effects included
      bleeding, pain/cramps, and nausea. Most women (92.6%) were satisfied/very
      satisfied with the method. Most providers who took the survey (85.6%) recommended
      that medical abortion be introduced at VINAFPA clinics. CONCLUSION: The
      operations research data demonstrate the safety, efficacy, and acceptability of
      medical abortion at VINAFPA clinics. The majority of surveyed providers endorsed
      adding medical abortion at their own facilities. Developing national guidelines
      for providing medical abortion at the clinic level is an important step in
      expanding access to services in Vietnam.

PMID- 22877841
TI  - Triticum mosaic poacevirus enlists P1 rather than HC-Pro to suppress RNA
      silencing-mediated host defense.
AB  - Triticum mosaic virus (TriMV) is the type species of the newly established
      Poacevirus genus in the family Potyviridae. In this study, we demonstrate that in
      contrast to the helper component-proteinase (HC-Pro) of Potyvirus species, the P1
      proteins of TriMV and Sugarcane streak mosaic poacevirus function in suppression
      of RNA silencing (SRS). TriMV P1 effectively suppressed silencing induced by
      single- or double-stranded RNAs (ss/ds RNAs), and disrupted the systemic spread
      of silencing signals at a step after silencing signal production. Interestingly,
      contrary to enhanced SRS activity of potyviral HC-Pro by co-expression with P1,
      the presence of TriMV HC-Pro reduced SRS activity of TriMV P1. Furthermore, TriMV
      P1 suppressed systemic silencing triggered by dsRNA more efficiently than the HC
      Pro of Turnip mosaic potyvirus. Furthermore, TriMV P1 enhanced the pathogenicity
      of a heterologous virus. Our results established poaceviral P1 as a potent RNA
      silencing suppressor that probably employs a novel mechanism to suppress RNA
      silencing-based antiviral defense.

PMID- 22877840
TI  - Functional anatomy of temporal organisation and domain-specificity of episodic
      memory retrieval.
AB  - Episodic memory provides information about the "when" of events as well as "what"
      and "where" they happened. Using functional imaging, we investigated the domain
      specificity of retrieval-related processes following encoding of complex,
      naturalistic events. Subjects watched a 42-min TV episode, and 24h later, made
      discriminative choices of scenes from the clip during fMRI. Subjects were
      presented with two scenes and required to either choose the scene that happened
      earlier in the film (Temporal), or the scene with a correct spatial arrangement
      (Spatial), or the scene that had been shown (Object). We identified a retrieval
      network comprising the precuneus, lateral and dorsal parietal cortex, middle
      frontal and medial temporal areas. The precuneus and angular gyrus are associated
      with temporal retrieval, with precuneal activity correlating negatively with
      temporal distance between two happenings at encoding. A dorsal fronto-parietal
      network engages during spatial retrieval, while antero-medial temporal regions
      activate during object-related retrieval. We propose that access to episodic
      memory traces involves different processes depending on task requirements. These
      include memory-searching within an organised knowledge structure in the precuneus
      (Temporal task), online maintenance of spatial information in dorsal fronto
      parietal cortices (Spatial task) and combining scene-related spatial and non
      spatial information in the hippocampus (Object task). Our findings support the
      proposal of process-specific dissociations of retrieval.

PMID- 22877842
TI  - Characterization of virulence-associated determinants in the envelope
      glycoprotein of Pichinde virus.
AB  - We use a small animal model, based on guinea pigs infected with a non-pathogenic
      Pichinde virus (PICV), to understand the virulence mechanisms of arenavirus
      infections in the hosts. PICV P2 strain causes a mild febrile reaction in guinea
      pigs, while P18 causes severe disease with clinical and pathological features
      reminiscent of Lassa hemorrhagic fever in humans. The envelope glycoproteins
      (GPC) of P2 and P18 viruses differ at positions 119, 140, and 164, all localized
      to the receptor-binding G1 subunit. We found that lentiviral pseudotyped virions
      (VLPs) bearing P18 GPC show more efficient cell entry than those with P2 GPC, and
      that the E140 residue plays a critical role in this process. Infection of guinea
      pigs with the recombinant viruses containing the E140K change demonstrated that
      E140 of GPC is a necessary virulence determinant of P18 infections, possibly by
      enhancing the ability of virus to enter target cells.

PMID- 22877843
TI  - Detection of substantial porcine group B rotavirus genetic diversity in the
      United States, resulting in a modified classification proposal for G genotypes.
AB  - Rotavirus (RV) is an important cause of gastrointestinal disease in animals and
      humans. In this study, we developed an RT-PCR to detect RV group B (RVB) and
      characterized the VP7 (G) gene segment detected in porcine samples. One hundred
      seventy three samples were tested for RV group A (RVA), RVB, and C (RVC) by RT
      PCR and examined for RV-like lesion using histopathology. A majority (86.4%) of
      the samples had mixed RV infections and co-infections of RVA/RVB/RVC were
      detected at a higher rate (24.3%) than previously reported. RVB was identified in
      46.8% of the 173 samples. An adapted VP7 classification was developed using
      previously published (n=57) and newly sequenced (n=68) RVB strains, resulting in
      20 G genotypes based on an 80% nucleotide identity cutoff value. Our results
      revealed a broad genetic diversity of porcine RVB strains, suggesting RVB has
      been the cause of common/pre-existing, yet undiagnosed, disease in pigs.

PMID- 22877844
TI  - The reliability of a rambling-trembling analysis of center of pressure measures.
AB  - The center of pressure (COP) measures are most commonly used in postural studies
      (e.g., COP range, sway path length and mean COP velocity). Relatively new method
      based on the equilibrium point hypothesis that addresses more explicitly the
      dynamic nature of COP and represents more subtle aspects of postural control is
      the rambling (RM) and trembling (TR) decomposition of a stabilogram. With this
      method, the COP trajectory can be decomposed into deviations resulting from
      supraspinal (i.e., RM) and spinal processes (i.e., TR). The trajectory generated
      by shifting COP is referred to as RM and its difference from the original COP
      signal is referred to as TR. Although there is still scientific discussion as to
      whether this method gives valuable additional information about postural control
      processes, it is gaining popularity. Unfortunately, there is lack of
      standardization in the methodology of data collection for this approach,
      particularly with respect to the number of trial repetitions and their duration.
      The objective of this study was to assess the reliability of RM-TR measurements.
      Fifteen young, healthy male subjects performed ten 120-s trials of quiet
      standing. Measurements of RM, TR and COP were calculated using the first 30, 60,
      90 and 120-s of each trial. An ANOVA-based ICC model was used to estimate the
      reliability. The results of this study suggest that at least three 60-s trials
      should be used when using selected measures of RM-TR.

PMID- 22877845
TI  - Quantitative estimation of foot-flat and stance phase of gait using foot-worn
      inertial sensors.
AB  - Time periods composing stance phase of gait can be clinically meaningful
      parameters to reveal differences between normal and pathological gait. This study
      aimed, first, to describe a novel method for detecting stance and inner-stance
      temporal events based on foot-worn inertial sensors; second, to extract and
      validate relevant metrics from those events; and third, to investigate their
      suitability as clinical outcome for gait evaluations. 42 subjects including
      healthy subjects and patients before and after surgical treatments for ankle
      osteoarthritis performed 50-m walking trials while wearing foot-worn inertial
      sensors and pressure insoles as a reference system. Several hypotheses were
      evaluated to detect heel-strike, toe-strike, heel-off, and toe-off based on
      kinematic features. Detected events were compared with the reference system on
      3193 gait cycles and showed good accuracy and precision. Absolute and relative
      stance periods, namely loading response, foot-flat, and push-off were then
      estimated, validated, and compared statistically between populations. Besides
      significant differences observed in stance duration, the analysis revealed
      differing tendencies with notably a shorter foot-flat in healthy subjects. The
      result indicated which features in inertial sensors' signals should be preferred
      for detecting precisely and accurately temporal events against a reference
      standard. The system is suitable for clinical evaluations and provides temporal
      analysis of gait beyond the common swing/stance decomposition, through a
      quantitative estimation of inner-stance phases such as foot-flat.

PMID- 22877846
TI  - Pluchea lanceolata (Rasana): Chemical and biological potential of Rasayana herb
      used in traditional system of medicine.
AB  - Pluchea lanceolata (DC.) Oliv. & Hiern, (Family: Asteraceae) is a rapidly
      spreading perennial herb, considered valuable for the management of anti
      inflammatory disease. Scientific reports dealing with phytochemical and
      pharmacological research and its traditional have been reviewed. Reports have
      also suggested that its prominent constituents viz. triterpenoids, sterols,
      flavonoids and lactones originate from this plant arbitrate their effects by
      modulating several therapeutic targets.Out of about 80 species of Pluchea, some
      of them are on extinct and only 16 have traditional uses in several countries of
      Asian, Middle East and North American region. The present review covers the
      period 1935-2011.

PMID- 22877847
TI  - Conditional survival of patients with metastatic renal-cell carcinoma treated
      with VEGF-targeted therapy: a population-based study.
AB  - BACKGROUND: The advent of targeted therapies in the past 7 years has extended
      median survival for metastatic renal-cell carcinoma. This improvement in clinical
      outcome has created a need for new, more accurate prognostic measures. We
      assessed the use of conditional survival--a measure that accounts for elapsed
      time since treatment initiation--for prognostication in patients with metastatic
      renal-cell carcinoma treated with first-line VEGF-targeted therapies. METHODS: We
      obtained data for patients with metastatic renal-cell carcinoma who were treated
      with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010,
      from our large multi-institutional International mRCC Database Consortium
      (centres in Canada, the USA, Singapore, Denmark, and South Korea). All
      histologies, performance statuses, and prognostic risk groups were included. The
      primary outcome was 2-year conditional survival, defined as the probability of
      surviving an additional 2 years from a given timepoint since the start of
      targeted therapy. Secondary analyses included 1-year and 3-year conditional
      survival, along with stratification of patients by Heng prognostic risk criteria
      and Karnofsky performance score, and conditional survival based on length of time
      on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate
      conditional survival. FINDINGS: In the 1673 patients analysed, median follow-up
      for alive patients was 20.1 months (IQR 9.0-34.4). We recorded an increase in the
      2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to
      51% (46-55) at 18 months since beginning targeted therapy. When stratified by the
      Heng prognostic risk criteria defined at therapy initiation, 2-year conditional
      survival changed little in the favourable and intermediate groups, but in the
      poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months
      to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from
      0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to
      68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the
      favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11%
      (8-15) to 73% (43-89) in the poor risk group. INTERPRETATION: Conditional
      survival is a clinically useful prediction measure that adjusts prognosis of
      patients with metastatic renal-cell carcinoma on the basis of survival since
      treatment initiation or therapy duration. Conditional survival might be
      especially relevant to adjust prognosis for poor-risk patients. FUNDING: The
      Trust Family Fund for Kidney Cancer Research.

PMID- 22877848
TI  - Temozolomide versus standard 6-week radiotherapy versus hypofractionated
      radiotherapy in patients older than 60 years with glioblastoma: the Nordic
      randomised, phase 3 trial.
AB  - BACKGROUND: Most patients with glioblastoma are older than 60 years, but
      treatment guidelines are based on trials in patients aged only up to 70 years. We
      did a randomised trial to assess the optimum palliative treatment in patients
      aged 60 years and older with glioblastoma. METHODS: Patients with newly diagnosed
      glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden,
      Switzerland, and Turkey. They were assigned by a computer-generated randomisation
      schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5
      of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy
      administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy
      administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were
      aware of treatment assignment. The primary endpoint was overall survival.
      Analyses were done by intention to treat. This trial is registered, number
      ISRCTN81470623. FINDINGS: 342 patients were enrolled, of whom 291 were randomised
      across three treatment groups (temozolomide n=93, hypofractionated radiotherapy
      n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two
      groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three
      group randomisation, in comparison with standard radiotherapy, median overall
      survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5;
      n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52
      0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6;
      n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide
      or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months
      [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06;
      p=0.12). For age older than 70 years, survival was better with temozolomide and
      with hypofractionated radiotherapy than with standard radiotherapy (HR for
      temozolomide vs standard radiotherapy 0.35 [0.21-0.56], p<0.0001; HR for
      hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02).
      Patients treated with temozolomide who had tumour MGMT promoter methylation had
      significantly longer survival than those without MGMT promoter methylation (9.7
      months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93],
      p=0.02), but no difference was noted between those with methylated and
      unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38];
      p=0.81). As expected, the most common grade 3-4 adverse events in the
      temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5
      infections in all randomisation groups were reported in 18 patients. Two patients
      had fatal infections (one in the temozolomide group and one in the standard
      radiotherapy group) and one in the temozolomide group with grade 2
      thrombocytopenia died from complications after surgery for a gastrointestinal
      bleed. INTERPRETATION: Standard radiotherapy was associated with poor outcomes,
      especially in patients older than 70 years. Both temozolomide and
      hypofractionated radiotherapy should be considered as standard treatment options
      in elderly patients with glioblastoma. MGMT promoter methylation status might be
      a useful predictive marker for benefit from temozolomide. FUNDING: Merck, Lion's
      Cancer Research Foundation, University of Umea, and the Swedish Cancer Society.

PMID- 22877849
TI  - Difficulty in predicting survival in metastatic renal cancer.

PMID- 22877850
TI  - Glioblastoma therapy in the elderly: one age does not fit all.

PMID- 22877851
TI  - EBEC 2012: combining the multiple facets of bioenergetics.

PMID- 22877853
TI  - Suppression of the nociceptive jaw-opening reflex by stimulation of the red
      nucleus.
AB  - We studied the effect of stimulation of the red nucleus (RN) on the jaw-opening
      reflex (JOR) in anesthetized rats. The JOR was evoked by electrical stimulation
      of the tooth pulp of a lower incisor, and was recorded as the electromyographic
      responses of the anterior belly of the digastric muscle, bilaterally.
      Conditioning electrical stimulation of the RN was found to suppress the JOR
      bilaterally. Microinjection of monosodium glutamate into the RN also suppressed
      the JOR bilaterally. The suppressive effect of the magnocellular part of the RN
      was significantly larger than that of the parvicellular part of the RN. These
      results imply that the RN is involved in control of the JOR evoked by noxious
      stimulus.

PMID- 22877852
TI  - Catechol and aldehyde moieties of 3,4-dihydroxyphenylacetaldehyde contribute to
      tyrosine hydroxylase inhibition and neurotoxicity.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder which leads
      to the selective loss of dopaminergic neurons. This causes a decrease in the
      important neurotransmitter dopamine (DA), which is essential for coordinated
      movement. Previous studies have implicated the monoamine oxidase metabolite of
      DA, 3,4-dihydroxphenylacetaldehyde (DOPAL), in the pathogenesis of PD and have
      shown it to be a reactive intermediate capable of protein modification. DOPAL
      also has demonstrated the ability to cause mitochondrial dysfunction and lead to
      significant inhibition of the rate-limiting enzyme in DA synthesis, tyrosine
      hydroxylase (TH). The current study was undertaken to investigate four analogs of
      DOPAL, including a novel nitrile analog, to determine how the structure of DOPAL
      is related to its toxicity and inhibition of TH. Both mitochondrial function and
      inhibition of TH in cell lysate were investigated. Furthermore, a novel whole
      cell assay was designed to determine the consequence to enzyme action when DOPAL
      levels were elevated. The results presented here demonstrate that changes to
      DOPAL structure lead to a decrease in toxicity and inhibition of enzyme activity
      as compared to the parent compound. Furthermore, the production of superoxide
      anion but not hydrogen peroxide increased in the presence of elevated DOPAL.
      These results reveal the toxicity of DOPAL and demonstrate that both the catechol
      and aldehyde are required to potently inhibit TH activity.

PMID- 22877855
TI  - [Cabazitaxel after docetaxel: a new option in metastatic castration-resistant
      prostate cancer].
AB  - The management of patients with metastatic castration-resistant prostate cancer
      is a real challenge. Indeed, after a first line chemotherapy with docetaxel,
      there was no standard because the treatments were ineffective. Today, several
      therapeutic options are available with the development of new therapies. Among
      them, cabazitaxel, semi-synthetic derivative of a natural taxoid, has been
      developed to its low recognition by the MDR system and power distribution
      including brain. This new chemotherapy was assessed in patients with metastatic
      castration-resistant prostate cancer whose disease has progressed during or after
      docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved
      overall survival of 2.4 months compared to mitoxantrone in the TROPIC phase III.
      However, hematologic toxicity may be limiting with a risk of febrile neutropenia;
      hematopoietic growth factors are advised in case of significant neutropenia. The
      cabazitaxel, Jevtana((r)), has been approved in second line after docetaxel. Its
      position in relation to new types of hormone therapy, as abiraterone acetate, in
      the same indication requires further investigations, including predictive factors
      of response. Studies are on going in first line indication (compared to
      docetaxel) and associated to other new hormone therapies.

PMID- 22877856
TI  - Association between anxiety but not depressive disorders and leukocyte telomere
      length after 2 years of follow-up in a population-based sample.
AB  - BACKGROUND: Telomere length is considered an emerging marker of biological aging.
      Depression and anxiety are associated with excess mortality risk but the
      mechanisms remain obscure. Telomere length might be involved because it is
      associated with psychological distress and mortality. The aim of this study was
      to test whether anxiety and depressive disorders predict telomere length over
      time in a large population-based sample. Method All analyses were performed in a
      longitudinal study in a general population cohort of 974 participants. The
      Composite International Diagnostic Interview (CIDI) was used to measure the
      presence of anxiety and depressive disorders. Telomere length was measured using
      monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of
      follow-up. We used linear multivariable regression models to evaluate the
      association between anxiety and depressive disorders and telomere length,
      adjusting for adverse life events, lifestyle factors, educational level and
      antidepressant use. RESULTS: The presence of anxiety disorders predicted shorter
      telomeres at follow-up (beta = -0.073, t = -2.302, p = 0.022). This association
      was similar after controlling for adverse life events, lifestyle factors,
      educational level and antidepressant use (beta = -0.077, t = -2.144, p = 0.032).
      No association was found between depressive disorders and shorter telomeres at
      follow-up (beta = 0.010, t = 0.315, p = 0.753). CONCLUSIONS: This study found
      that anxiety disorders predicted shorter telomere length at follow-up in a
      general population cohort. The association was not explained by adverse life
      events, lifestyle factors, educational level and antidepressant use. How anxiety
      disorders might lead to accelerated telomere shortening and whether this might be
      a mediator explaining the excess mortality risk associated with anxiety deserve
      further investigation.

PMID- 22877857
TI  - [Medication errors in neonatal medicine: from prescription to administration].
AB  - Neonatal units have the highest incidence of medication errors (approximately 5%)
      compared to adult and pediatric wards. Medication errors include prescribing
      errors, transcription errors, dispensing errors, medication administration
      errors, and monitoring. Dosing error is the most common prescribing error.
      Prevention of medication error must be global. The implementation of a
      computerized physician order entry significantly reduces prescribing errors but
      other preventive measures remain necessary.

PMID- 22877858
TI  - [Autism and prematurity: state of the art].
AB  - Research has shown a high rate of autism spectrum disorders among very low birth
      weight children over the past decade. This paper proposes a literature review on
      this topic. Two generations of research have followed one another. The first
      retrospective studies found a high rate of ASD among premature babies. The second
      generation of prospective studies underlined and relativized this risk.
      Prospective research using screening tools (M-CHAT) have found around 20 % ASD,
      whereas 2 studies assessing the actual diagnosis found 5 % and 8 % ASD, 10 to 12
      times more than in the general population. A number of hypotheses have been put
      forward to explain these high rates of ASD: sensory impairment associated with
      prematurity, white matter abnormalities, and cerebellar impairment. The authors
      propose complex models that take into account neurological deficits and the
      effects of perinatal events on interactive dynamics between infants and their
      caregivers. These models aim to allow suitable prevention and care for premature
      children with autism, a heavy additional handicap.

PMID- 22877859
TI  - [Clinical presentation of inborn metabolic diseases in the neonatal period].
AB  - Inborn metabolic diseases (IMDs) that can start in the neonatal period include
      various defects in numerous metabolic pathways. Such diseases are due to the
      genetic deficiency of an enzyme or a transporter. From a physiopathological point
      of view, the metabolic disorders can be divided into 3 diagnostically useful
      groups of diseases. The first group is due to the accumulation of endogenous
      toxic metabolites and includes inborn errors of amino acid metabolism, organic
      acidemias, urea cycle disorders, and sugar intolerances. The second one includes
      IMDs of intermediary metabolism causing a disturbance in energy production or
      utilization resulting from a defect in the liver, the muscles, the myocardium, or
      the brain (fatty acid oxidation defects, congenital lactic acidosis, etc.). The
      third group includes diseases that disturb the synthesis or the catabolism of
      complex molecules (lysosomal or peroxisomal disorders, etc.). IMDs are
      individually rare, but collectively numerous. Therefore, it is difficult to
      acquire extensive experience in the management of these diseases. However, the
      neonate has a limited repertoire of responses to severe illness and, at first,
      presents with nonspecific symptoms that could be easily attributed to infection
      or some other common cause. An IMD must be suspected in all situations of
      neonatal distress for which there is no apparent reason and that does not respond
      to symptomatic therapy. The priority is given to IMDs that are amenable to
      treatment, and emergency management has to be scheduled as soon as the diagnosis
      is suspected, even if the precise diagnosis is still unknown. In fact, emergency
      treatment must be undertaken in parallel with metabolic investigations, to
      prevent any delay in the management of the disease. The neonatologist must be
      able to recognize the neonatal distresses that suggest the possibility of an IMD.
      In such situations, an adequate diagnostic approach can be based on the proper
      use of only a few screening tests, which will also be useful to schedule adequate
      emergency treatment.

PMID- 22877860
TI  - Potential T cell epitopes within swine-origin triple reassortant influenza A
      (H3N2) variant virus which emerged in 2011: an immunoinformatics study.
AB  - An immuno-informatics study was conducted to determine possible pre-existing T
      cellular immunity to the recently emerged swine-origin triple reassortant H3N2
      variant (S-OtrH3N2v-2011) which acquired the matrix gene of influenza A
      (H1N1)pdm09. Given the genetic origin of S-OtrH3N2v-2011, our study focused on
      the hemagglutinin (HA) and matrix1 (M1) proteins to identify common and conserved
      T cell epitopes. We compared HA CD4+ T cell epitopes of S-OtrH3N2v-2011 with
      seasonal H3N2 (1968-2011)-HA proteins. M1 CD4+ and CD8+ T cell epitopes of S
      OtrH3N2v-2011 were compared with the M1 proteins of seasonal H1N1 (1977-2009) and
      A (H1N1)pdm09 (2009-2011) subtypes. The results revealed a high conservancy of
      epitopes localized particularly on HA2 and the entire M1 protein. The overall
      cross reactivity of predicted CD4+ T cell epitopes with previously experimentally
      defined (Immuno Epitope Database) CD4+ T epitopes of HA and M1 proteins was ~51%.
      CD8+ T cell cross-reactivity of ~74% was documented for M1 protein. Analysis
      suggests possible pre-existing CD4+ T cell immunity to S-OtrH3N2v-2011 in the
      human population.

PMID- 22877861
TI  - The role of metacognition, intolerance of uncertainty, and negative problem
      orientation in children's worry.
AB  - BACKGROUND: Although worry is common in children, empirical models of worry
      remain largely untested in youth. A small number of studies have established
      preliminary links between cognitive variables and worry in children younger than
      12 years old. These cognitive variables include positive and negative beliefs
      about worry, intolerance of uncertainty, and problem orientation. AIMS: The
      current study examined these variables concurrently and their association with
      worry. We also examined the extent to which intolerance of uncertainty mediated
      the association between worry and beliefs about worry. METHOD: Eighty elementary
      school children aged 8 to 12 years completed a battery of self-report measures.
      RESULTS: As a group, the cognitive variables significantly predicted worry
      scores; negative beliefs about worry was the only significant individual
      predictor. As a group, the four cognitive variables discriminated clinical from
      nonclinical levels of worry; positive beliefs about worry and intolerance of
      uncertainty were the only significant individual predictors. Finally, intolerance
      of uncertainty mediated the association between worry and both positive and
      negative beliefs about worry. CONCLUSIONS: Components of a cognitive model of
      worry are largely applicable to children. Negative beliefs about worry were
      associated with worry across the continuum, while intolerance of uncertainty and
      positive beliefs about worry were more strongly associated with clinical levels
      of worry. Intolerance of uncertainty accounted for a significant portion of the
      association between metacognition and worry and may be a particularly effective
      target for treatment. Further implications for conceptual models and treatment
      interventions are discussed.

PMID- 22877862
TI  - Burn caused by rinse aid.

PMID- 22877863
TI  - BioJava: an open-source framework for bioinformatics in 2012.
AB  - BioJava is an open-source project for processing of biological data in the Java
      programming language. We have recently released a new version (3.0.5), which is a
      major update to the code base that greatly extends its functionality. RESULTS:
      BioJava now consists of several independent modules that provide state-of-the-art
      tools for protein structure comparison, pairwise and multiple sequence
      alignments, working with DNA and protein sequences, analysis of amino acid
      properties, detection of protein modifications and prediction of disordered
      regions in proteins as well as parsers for common file formats using a
      biologically meaningful data model. AVAILABILITY: BioJava is an open-source
      project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from
      the BioJava website (http://www.biojava.org). BioJava requires Java 1.6 or
      higher. All inquiries should be directed to the BioJava mailing lists. Details
      are available at http://biojava.org/wiki/BioJava:MailingLists.

PMID- 22877864
TI  - PPfold 3.0: fast RNA secondary structure prediction using phylogeny and auxiliary
      data.
AB  - PPfold is a multi-threaded implementation of the Pfold algorithm for RNA
      secondary structure prediction. Here we present a new version of PPfold, which
      extends the evolutionary analysis with a flexible probabilistic model for
      incorporating auxiliary data, such as data from structure probing experiments.
      Our tests show that the accuracy of single-sequence secondary structure
      prediction using experimental data in PPfold 3.0 is comparable to RNAstructure.
      Furthermore, alignment structure prediction quality is improved even further by
      the addition of experimental data. PPfold 3.0 therefore has the potential of
      producing more accurate predictions than it was previously possible. AVAILABILITY
      AND IMPLEMENTATION: PPfold 3.0 is available as a platform-independent Java
      application and can be downloaded from http://birc.au.dk/software/ppfold.

PMID- 22877865
TI  - Antimicrobial properties of cyclodextrin-antiseptics-complexes determined by
      microplate laser nephelometry and ATP bioluminescence assay.
AB  - Antimicrobial effects of substances can be determined with different methods that
      measure distinct parameters. Thus, a comparison of the results obtained can be
      difficult. In this study, two in vitro methods were employed to determine
      concentration and time dependent effects of cyclodextrin (CD)-complexes with the
      antiseptics chlorhexidine diacetate (CHX), iodine (IOD) and polihexanide (PHMB)
      on Candida albicans and Malassezia pachydermatis. Using both, microplate laser
      nephelometry and the ATP bioluminescence assay, it could be shown that CD
      antiseptics-complexes tested exhibited significant antifungal effects with the
      exception of gamma-CD-CHX in the case of C. albicans. Microplate laser
      nephelometry (MLN) is an optical method and enables a quantitative determination
      of particle concentrations in solution. By means of this method, microbial growth
      under influence of potential antimicrobial substances can be monitored over a
      prolonged time period. In addition, the antimicrobial activity was analyzed by
      measurement of the microbial adenosine triphosphate (ATP) content with a
      bioluminescent assay. The luminescent signal is directly proportional to the
      amount of ATP, and thus, a linear function of the number of living microbial
      cells present. Both methods were compared according to the half maximal
      inhibitory concentration (IC(50)) calculated and the statistical evaluation of
      Pearson's correlation coefficient (r). In summary, it could be demonstrated that
      both methods yield similar results although they differ in the parameter.

PMID- 22877866
TI  - Long-term clinical outcome after intramuscular transplantation of granulocyte
      colony stimulating factor-mobilized CD34 positive cells in patients with critical
      limb ischemia.
AB  - BACKGROUND: Our phase I/IIa clinical trial revealed that intramuscular
      transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and
      potentially effective at week 4 and 12 post cellular therapy in 17 patients with
      chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral
      arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome
      of the cell therapy has yet to be reported. METHODS AND RESULTS: Incidence of
      major clinical events and physiological parameters of limb ischemia were
      evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died
      by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with
      Buerger's disease died by week 208 due to cardiac complications. No patients
      underwent major amputation, whereas 1 patient with Buerger's disease underwent
      unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and
      104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant
      improvement of toe brachial pressure index versus baseline was sustained up to
      week 208 and that of transcutaneous partial oxygen pressure was kept up to week
      156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance
      significantly improved at week 52, the final evaluation time point, compared with
      baseline. Subgroup analysis revealed the similar outcome in patients with
      Buerger's disease. CONCLUSIONS: Favorable clinical outcomes as well as
      physiological evidences strongly indicate the long-term benefit of GCSF-mobilized
      CD34+ cell transplantation for retrieval from CLI, especially in patients with
      Buerger's disease.

PMID- 22877867
TI  - Detection of hydroxyapatite in calcified cardiovascular tissues.
AB  - OBJECTIVE: The objective of this study is to develop a method for selective
      detection of the calcific (hydroxyapatite) component in human aortic smooth
      muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This
      method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target
      calcified cells and tissues. METHODS: A peptide that mimics the binding affinity
      of osteocalcin was used to label hydroxyapatite in vitro and ex vivo.
      Morphological changes in vascular smooth muscle cells were evaluated at an early
      stage of the mineralization process induced by extrinsic stimuli, osteogenic
      factors and a magnetic suspension cell culture. Hydroxyapatite components were
      detected in monolayers of these cells in the presence of osteogenic factors and a
      magnetic suspension environment. RESULTS: Atherosclerotic plaque contains
      multiple components including lipidic, fibrotic, thrombotic, and calcific
      materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we
      demonstrated that hydroxyapatite components could be selectively distinguished
      from various calcium salts in human aortic smooth muscle cells in vitro and in
      calcified cardiovascular tissues, carotid endarterectomy samples and aortic
      valves, ex vivo. CONCLUSION: Hydroxyapatite deposits in cardiovascular tissues
      were selectively detected in the early stage of the calcification process using
      our Cy-HABP-19 probe. This new probe makes it possible to study the earliest
      events associated with vascular hydroxyapatite deposition at the cellular and
      molecular levels. This target-selective molecular imaging probe approach holds
      high potential for revealing early pathophysiological changes, leading to
      progression, regression, or stabilization of cardiovascular diseases.

PMID- 22877868
TI  - Decaffeinated green tea extract improves hypertension and insulin resistance in a
      rat model of metabolic syndrome.
AB  - BACKGROUND: Oxidative stress and endothelial dysfunction are closely associated
      with hypertension and insulin resistance (IR) in metabolic syndrome (MetS). It is
      still controversial whether green tea extract (GTE) may have blood pressure (BP)
      lowering effect. Decaffeinated GTE might be presumed to have strong antioxidative
      effect and BP-lowering effect as compared with catechins. Thus we investigated
      whether decaffeinated-GTE could attenuate hypertension and IR by improving
      endothelial dysfunction and reducing oxidative stress in a rat model of MetS.
      METHODS AND RESULTS: 20 Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 13
      weeks old, MetS rats, were randomized into a saline treated group (OLETF; n = 10)
      and a group treated with decaffeinated-GTE (25 mg/kg/day) (GTE-OLETF; n = 10).
      Intraperitoneal glucose tolerance tests and BP measurements were performed at 13
      and 25 weeks. Decaffeinated-GTE significantly reduced BP (OLETF vs. GTE-OLETF;
      130 +/- 7 vs. 121 +/- 3 mmHg, p = 0.01), fasting/postprandial 2 h glucose (141 +/
      18/159 +/- 13 vs. 115 +/- 7/132 +/- 16 mg/dL, p = 0.009/0.002) and insulin
      levels (4.8 +/- 2.3 vs. 2.4 +/- 1.3 ng/mL, p < 0.001). Decaffeinated-GTE
      significantly reduced vascular reactive oxygen species (ROS) formation and NADPH
      oxidase activity, and improved endothelium dependent relaxation in the thoracic
      aorta of OLETF rats. Decaffeinated-GTE also suppressed the expression of p47 and
      p22phox (NADPH oxidase subunits) in the immunohistochemical staining, and
      stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) and Akt in
      the immunoblotting of aortas. CONCLUSIONS: Decaffeinated-GTE reduced the
      formation of ROS and NADPH oxidase activity and stimulated phosphorylation of
      eNOS and Akt in the aorta of a rat model of MetS, which resulted in improved
      endothelial dysfunction and IR, and eventually lowered BP.

PMID- 22877870
TI  - The influence of local effects on thermal sensation under non-uniform
      environmental conditions--gender differences in thermophysiology, thermal comfort
      and productivity during convective and radiant cooling.
AB  - Applying high temperature cooling concepts, i.e. high temperature cooling
      (T(supply) is 16-20 degrees C) HVAC systems, in the built environment allows the
      reduction in the use of (high quality) energy. However, application of high
      temperature cooling systems can result in whole body and local discomfort of the
      occupants. Non-uniform thermal conditions, which may occur due to application of
      high temperature cooling systems, can be responsible for discomfort.
      Contradictions in literature exist regarding the validity of the often used
      predicted mean vote (PMV) index for both genders, and the index is not intended
      for evaluating the discomfort due to non-uniform environmental conditions. In
      some cases, however, combinations of local and general discomfort factors, for
      example draught under warm conditions, may not be uncomfortable. The objective of
      this study was to investigate gender differences in thermophysiology, thermal
      comfort and productivity in response to thermal non-uniform environmental
      conditions. Twenty healthy subjects (10 males and 10 females, age 20-29 years)
      were exposed to two different experimental conditions: a convective cooling
      situation (CC) and a radiant cooling situation (RC). During the experiments
      physiological responses, thermal comfort and productivity were measured. The
      results show that under both experimental conditions the actual mean thermal
      sensation votes significantly differ from the PMV-index; the subjects are feeling
      colder than predicted. Furthermore, the females are more uncomfortable and
      dissatisfied compared to the males. For females, the local sensations and skin
      temperatures of the extremities have a significant influence on whole body
      thermal sensation and are therefore important to consider under non-uniform
      environmental conditions.

PMID- 22877869
TI  - Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and
      epidermal keratinocytes.
AB  - The discovery that 7-dehydrocholesterol (7DHC) is an excellent substrate for
      cytochrome P450scc (CYP11A1) opens up new possibilities in biochemistry. To
      elucidate its biological significance we tested ex vivo P450scc-dependent
      metabolism of 7DHC by tissues expressing high and low levels of P450scc activity,
      placenta and epidermal keratinocytes, respectively. Incubation of human placenta
      fragments with 7DHC led to its conversion to 7-dehydropregnenolone (7DHP), which
      was inhibited by dl-aminoglutethimide, and stimulated by forskolin. Final proof
      for P450scc involvement was provided in isolated placental mitochondria where
      production of 7DHP was almost completely inhibited by 22R-hydroxycholesterol.
      7DHC was metabolized by placental mitochondria at a faster rate than exogenous
      cholesterol, under both limiting and saturating conditions of substrate
      transport, consistent with higher catalytic efficiency (k(cat)/K(m)) with 7DHC as
      substrate than with cholesterol. Ex vivo experiments showed five 5,7-dienal
      intermediates with MS spectra of dihydroxy and mono-hydroxy-7DHC and retention
      time corresponding to 20,22(OH)(2)7DHC and 22(OH)7DHC. The chemical structure of
      20,22(OH)(2)7DHC was defined by NMR. 7DHP was further metabolized by either
      placental fragments or placental microsomes to 7-dehydroprogesterone as defined
      by UV, MS and NMR, and to an additional product with a 5,7-dienal structure and
      MS corresponding to hydroxy-7DHP. Furthermore, epidermal keratinocytes
      transformed either exogenous or endogenous 7DHC to 7DHP. 7DHP inhibited
      keratinocytes proliferation, while the product of its pholytic transformation,
      pregcalciferol, lost this capability. In conclusion, tissues expressing P450scc
      can metabolize 7DHC to biologically active 7DHP with 22(OH)7DHC and
      20,22(OH)(2)7DHC serving as intermediates, and with further metabolism to 7
      dehydroprogesterone and (OH)7DHP.

PMID- 22877871
TI  - Synthesis and biological evaluation of tyrosine modified analogues of the
      alpha4beta7 integrin inhibitor biotin-R8ERY.
AB  - The alpha4beta7 integrin is a well-known target for the development of drugs
      against various inflammatory disease states including inflammatory bowel disease,
      type 1 diabetes and multiple sclerosis. The synthesis of a small library of cell
      permeable beta7 integrin inhibitors based on the peptide biotin-R(8)ERY is
      reported, in which the tyrosine residue has been modified by using the Suzuki
      Miyaura cross-coupling reaction. The synthesised peptidomimetics were evaluated
      in a cell adhesion assay and shown to inhibit Mn(2+)-activated adhesion of mouse
      TK-1 T cells to mouse MAdCAM-1. All of the synthesised peptidomimetics are more
      active than our previously reported lead compound biotin-R(8)ERY with two of the
      analogues, 6 and 7, exhibiting IC(50) values of <15 MUM.

PMID- 22877873
TI  - Quantitative proton nuclear magnetic resonance evaluation and total assignment of
      the capsular polysaccharide Neisseria meningitidis serogroup X.
AB  - Neisseria meningitidis constitutes the main cause of meningococcal disease in
      infants. Serogroups A, B, C, W135, Y, and X have the higher incidence in young
      children and teenagers. The use of polyvalent conjugate carbohydrate-based
      vaccines has decreased the meningococcal infection around the world. Recently,
      the serogroup X has been found to be responsible of different outbreaks of
      meningococcal diseases, mainly in "Meningitis Belt" of Africa and the structure
      of the repetitive unit of the capsular polysaccharide has been confirmed through
      a monodimensional (13)C NMR study. No further characterization studies have been
      carried out, especially with the use of other nuclei. In this paper a novel
      method for quantification of the N. meningitidis serogroup X by proton qNMR is
      reported. Deep characterization of the serogroup X polysaccharide was also
      carried out by combination of correlation experiments involving (13)C, (1)H, and
      (31)P nuclei.

PMID- 22877872
TI  - Sugar-modified derivatives of cytostatic 7-(het)aryl-7-deazaadenosines: 2'-C
      methylribonucleosides, 2'-deoxy-2'-fluoroarabinonucleosides, arabinonucleosides
      and 2'-deoxyribonucleosides.
AB  - A series of novel sugar-modified derivatives of cytostatic 7-hetaryl-7
      deazaadenosines (2'-C-methylribonucleosides, 2'-deoxy-2'
      fluoroarabinonucleosides, arabinonucleosides and 2'-deoxyribonucleosides) was
      prepared and screened for biological activity. The synthesis consisted of
      preparation of the corresponding sugar-modified 7-iodo-7-deazaadenine nucleosides
      and their aqueous-phase Suzuki-Miyaura cross-coupling reactions with
      (het)arylboronic acids or Stille couplings with hetarylstannanes in DMF. The
      synthesis of 7-iodo-7-deazaadenine nucleosides was based on a glycosidation of 6
      chloro-7-iodo-7-deazapurine with a suitable sugar synthon or on an
      interconversion of 2'-OH stereocenter (for arabinonucleosides). Several examples
      of 2'-C-Me-ribonucleosides showed moderate anti-HCV activities in a replicon
      assay accompanied by cytotoxicity. Several 7-hetaryl-7-deazaadenine fluoroarabino
      and arabinonucleosides exerted moderate micromolar cytostatic effects. The most
      active was 7-ethynyl-7-deazaadenine fluoroarabinonucleoside which showed
      submicromolar antiproliferative activity. However, all the sugar-modified
      derivatives were less active than the parent ribonucleosides.

PMID- 22877874
TI  - Arrays of SnO2 nanorods as novel solid phase microextraction for trace analysis
      of antidepressant drugs in body fluids.
AB  - The arrays of tin oxide nanorods-solid phase microextraction (ATN-SPME) fibre
      coupled with the high performance liquid chromatography (HPLC) method was
      developed for simultaneous determination of selective serotonin reuptake
      inhibitors (SSRI), citalopram and fluoxetine, in human urine and plasma samples.
      The variables of interest in the Direct-SPME (D-SPME) were extraction time, pH,
      ion strength or salt percentage and desorption time of analytes from the fibre.
      These factors were optimised by using a Box-Behnken design and the response
      surface equations were developed. The optimal experimental conditions obtained
      from this statistical evaluation included: the salt percentage (30%, w/v), NaOH
      volume (6.5 MUl from a 1 M solution), extraction time (10 min) and desorption
      time (30 min) for drugs in the plasma sample and The salt percentage (30%, w/v),
      NaOH volume (100 MUl from a 1 M solution), extraction time (18 min) and
      desorption time (23 min) for drugs in the urine sample. A satisfactory
      reproducibility for the extraction from urine and plasma samples (R.S.D.<10%) was
      obtained. The linearity for urine and plasma ranged from 1 to 5*10(5) ng ml(-1)
      with a detection limit of 0.2 ng ml(-1) for citalopram and 0.5 ng ml(-1) for
      fluoxetine, which covered the typical urinary concentrations obtained for
      citalopram and fluoxetine.

PMID- 22877875
TI  - Tris(hydroxymethyl) aminomethane salt of ramipril: synthesis, structural
      characterization from X-ray powder diffraction and stability studies.
AB  - Tris(hydroxymethyl) aminomethane (tris) salt of API ramipril was synthesized, and
      characterized by FTIR, TG-DSC and ab initio X-ray powder structure analysis. The
      compound, ramipril-tris (II), crystallizes in the monoclinic space group P2(1)
      with a=24.3341(15), b=6.4645(5), c=9.5357(7) A, beta=96.917(3) degrees  and
      V=1489.1(3) A(3). The crystal structure has been determined from laboratory X-ray
      powder diffraction data using direct space global optimization strategy
      (simulated annealing) followed by the Rietveld refinement. A network of
      intermolecular OH...O, CH...N and CH...O hydrogen bonds between the ramipril
      ramipril, tris-tris and ramipril-tris components in the compound generates a two
      dimensional molecular assembly in (110) plane. A comparative study of solid-state
      stabilities of ramipril-tris (II) with that of ramipril (I) and ramipril-erbumine
      (III) indicates that ramipril-tris (II) is the most stable one among the three,
      and the conversion to impurity D after 72 h at 80  degrees C is only 1.5%. The
      solution phase analysis at different pH values also reveals a greater stability
      of ramipril-tris (II) over ramipril (I).

PMID- 22877876
TI  - Heritability of strabismus: genetic influence is specific to eso-deviation and
      independent of refractive error.
AB  - Strabismus represents a complex oculomotor disorder characterized by the
      deviation of one or both eyes and poor vision. A more sophisticated understanding
      of the genetic liability of strabismus is required to guide searches for
      associated molecular variants. In this classical twin study of 1,462 twin pairs,
      we examined the relative influence of genes and environment in comitant
      strabismus, and the degree to which these influences can be explained by factors
      in common with refractive error. Participants were examined for the presence of
      latent ('phoria') and manifest ('tropia') strabismus using cover-uncover and
      alternate cover tests. Two phenotypes were distinguished: eso-deviation
      (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural
      equation modeling was subsequently employed to partition the observed phenotypic
      variation in the twin data into specific variance components. The prevalence of
      eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso
      deviation, the polychoric correlation was significantly greater in monozygotic
      (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a
      genetic role (p = .003). There was no significant difference in polychoric
      correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation
      (p = .86), implying that genetic factors do not play a significant role in the
      etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI
      0.50-0.75). The additive genetic correlation for eso-deviation and refractive
      error was 0.13 and the bivariate heritability (i.e., shared variance) was less
      than 1%, suggesting negligible shared genetic effect. This study documents a
      substantial heritability of 64% for eso-deviation, yet no corresponding
      heritability for exo-deviation, suggesting that the genetic contribution to
      strabismus may be specific to eso-deviation. Future studies are now needed to
      identify the genes associated with eso-deviation and unravel their mechanisms of
      action.

PMID- 22877877
TI  - Photochemical induced changes of in vitro estrogenic activity of steroid
      hormones.
AB  - Steroid estrogens are endocrine disrupting contaminants frequently detected in
      natural waters. Because these estrogens can elicit significant biological
      responses in aquatic organisms, it is important to study their rates and pathways
      of degradation in natural waters and to identify whether the transformation
      products retain biological activity. Photochemical kinetics experiments were
      conducted under simulated solar light for the hormones 17beta-estradiol (E2),
      17alpha-ethinylestradiol (EE2), estrone (E1), equilin (EQ), and equilenin (EQN)
      under direct and indirect photolysis conditions. All of these hormones were
      susceptible to direct photodegradation, with half-lives ranging from 40 min for
      E1 to about 8 h for E2 and EE2. Indirect photolysis experiments with added
      Suwannee River fulvic acid (SRFA) lead to faster degradation rates for E2, EE2,
      and EQ. Added SRFA caused slower photodegradation rates for E1 and EQN,
      indicating that it acts primarily as an inner filter for these analytes. The well
      established yeast estrogen screen (YES) was used to measure the estrogenicity of
      the analytes and their photoproducts. Results of YES assay experiments show that
      only the direct photolysis of E1 gave estrogenic products. Lumiestrone, the major
      E1 direct photolysis product, was isolated and characterized. It formed in 53%
      yield and exhibited moderate estrogenic activity. When photolysed in the presence
      of perinaphthenone, a potent synthetic sensitizer, E1 degraded via an indirect
      photolysis pathway and did not produce lumiestrone or any other active products.
      These results suggest that under typical natural water conditions photochemical
      reactions of E2, EE2, EQ, and EQN are expected to produce inactive products while
      E1 will give the estrogenic product lumiestrone in moderate yield.

PMID- 22877878
TI  - Identification of the attenuation potential of a karst aquifer by an artificial
      dualtracer experiment with caffeine.
AB  - Little is known with respect to the attenuation capacity of karst aquifers. Even
      less is known about the risk posed by emerging micropollutants in these systems.
      In order to identify the attenuation potential of karst aquifers in-situ and to
      estimate the risk posed by micropollutants, a dualtracer test was conducted in
      this study in order to investigate differential transport in the subsurface: The
      reactive compound caffeine was used as a tracer to indicate the attenuation
      capacity within the aquifer in-situ. Due to the low limit of quantification, only
      small amounts of caffeine needed to be injected. To calibrate a model and to
      visualize the attenuation of caffeine a conservative reference tracer (uranine)
      is injected simultaneously. The methodology is tested in a well-characterised
      karst system in southwest Germany. The results indicate a significantly higher
      attenuation rate than was expected for karst aquifers. The attenuation is
      decribed as a first-order process. The corresponding half-life is 104 h. This low
      half-life suggests that a generally assumed low natural attenuation capacity of
      karst aquifers is unjustified. The observed mass loss of caffeine illustrates the
      potential of caffeine to be used as reactive tracer for indicating in-situ
      attenuation capacity within highly hydraulically conductive systems, such as
      karst aquifers. Due to the high attenuation rate of caffeine it does not pose a
      threat as a long-time contaminant. In combination with a conservative reference
      tracer an economical and environmentally benign method is presented in this
      manuscript for the in-situ determination of the attenuation capacity of highly
      conductive aquifer systems.

PMID- 22877879
TI  - Dynamic modeling of biodegradation and volatilization of hazardous aromatic
      substances in aerobic bioreactor.
AB  - The aerobic biological process is one of the best technologies available for
      removing hazardous organic substances from industrial wastewaters. But in the
      case of volatile organic compounds (benzene, toluene, ethylbenzene, p-xylene,
      naphthalene), volatilization can contribute significantly to their removal from
      the liquid phase. One major issue is to predict the competition between
      volatilization and biodegradation in biological process depending on the target
      molecule. The aim of this study was to develop an integrated dynamic model to
      evaluate the influence of operating conditions, kinetic parameters and physical
      properties of the molecule on the main pathways (biodegradation and
      volatilization) for the removal of Volatile Organic Compounds (VOC). After a
      comparison with experimental data, sensitivity studies were carried out in order
      to optimize the aerated biological process. Acclimatized biomass growth is
      limited by volatilization, which reduces the bioavailability of the substrate.
      Moreover, the amount of biodegraded substrate is directly proportional to the
      amount of active biomass stabilized in the process. Model outputs predict that
      biodegradation is enhanced at high SRT for molecules with low H and with a high
      growth rate population. Air flow rate should be optimized to meet the oxygen
      demand and to minimize VOC stripping. Finally, the feeding strategy was found to
      be the most influential operating parameter that should be adjusted in order to
      enhance VOC biodegradation and to limit their volatilization in sequencing batch
      reactors (SBR).

PMID- 22877880
TI  - Effect of chlorination condition and permeability of chlorine species on the
      chlorination of a polyamide membrane.
AB  - Most studies on membrane chlorination have been investigated in an unpressurized
      chlorination mode, even if the polyamide membrane was continuously exposed to
      chlorine under high operating pressure in real water/wastewater treatment plants.
      In this study, performance changes due to polyamide membrane chlorination were
      investigated in both pressurized and unpressurized chlorination modes.
      Chlorination in an unpressurized mode showed a flux increase at high pH and a
      flux decline at low pH due to the compaction and swelling of the polyamide
      chains, respectively. On the other hand, chlorination performed in a pressurized
      mode decreased the water flux in both acidic and alkaline conditions, showing
      that compaction is overwhelming compared to swelling. The permeability of HOCl, a
      dominant species at low pH, through the polyamide membrane was pH independent and
      almost similar to the system recovery, but the permeability of OCl(-), which is
      dominant at high pH, was maxima at a neutral pH. The different performance
      behaviors of membranes chlorinated at various pH conditions in the presence or
      absence of applied pressure could be explained by the permeability of chlorine
      species and compaction/swelling of polymer chains after chlorination. The effect
      of membrane chlorination on the chemical property changes at the two different
      modes was confirmed using attenuated total reflection Fourier transform infrared
      analysis, and a conceptual model of performance change was proposed to explain
      the performance discrepancy between the two chlorination modes.

PMID- 22877881
TI  - Assessing the performance of sewer rehabilitation on the reduction of
      infiltration and inflow.
AB  - Inflow and Infiltration (I/I) into sewer systems is generally unwanted, because,
      among other things, it decreases the performance of wastewater treatment plants
      and increases combined sewage overflows. As sewer rehabilitation to reduce I/I is
      very expensive, water managers not only need methods to accurately measure I/I,
      but also they need sound approaches to assess the actual performance of
      implemented rehabilitation measures. However, such performance assessment is
      rarely performed. On the one hand, it is challenging to adequately take into
      account the variability of influential factors, such as hydro-meteorological
      conditions. On the other hand, it is currently not clear how experimental data
      can indeed support robust evidence for reduced I/I. In this paper, we therefore
      statistically assess the performance of rehabilitation measures to reduce I/I.
      This is possible by using observations in a suitable reference catchment as a
      control group and assessing the significance of the observed effect by regression
      analysis, which is well established in other disciplines. We successfully
      demonstrate the usefulness of the approach in a case study, where rehabilitation
      reduced groundwater infiltration by 23.9%. A reduction of stormwater inflow of
      35.7%, however, was not statistically significant. Investigations into the
      experimental design of monitoring campaigns confirmed that the variability of the
      data as well as the number of observations collected before the rehabilitation
      impact the detection limit of the effect. This implies that it is difficult to
      improve the data quality after the rehabilitation has been implemented.
      Therefore, future practical applications should consider a careful experimental
      design. Further developments could employ more sophisticated monitoring methods,
      such as stable environmental isotopes, to directly observe the individual
      infiltration components. In addition, water managers should develop strategies to
      effectively communicate statistically not significant I/I reduction ratios to
      decision makers.

PMID- 22877882
TI  - Influence of nitrifying conditions on the biodegradation and sorption of emerging
      micropollutants.
AB  - High biodegradation efficiencies of different emerging micropollutants were
      obtained with nitrifying activated sludge (NAS) working at high nitrogen loading
      rates (NLR), that boosted the development of biomass with high nitrifying
      activities (>1 g N-NH(4)(+)/g VSS d). Come-tabolic biodegradation seemed to be
      responsible for the removal of most compounds due to the action of the ammonium
      monooxygenase enzyme. NAS showed a different affinity for each compound, probably
      due to steric hindrance, activation energy limitations or the presence of
      specific functional groups. Increasing loading rates of micropollutants were
      removed at shorter hydraulic retention times, although the biodegradation
      efficiencies of compounds with slow/intermediate kinetics, such as fluoxetine,
      erythromycin, roxithromycin and trimethoprim, diminished due to kinetic and/or
      stoichiometric limitations. Solids retention time, always above the minimum to
      avoid the washout of nitrifiers, did not enhance the biodegradation of any of the
      selected compounds, with the exception of diclofenac. Regarding sorption, the
      solid-liquid distribution coefficients (K(d)) obtained in NAS were very similar
      to those found in conventional activated sludge by other authors. No correlation
      between K(d) values and any of the operational parameters was found for the
      selected substances.

PMID- 22877883
TI  - [Cytogenomic studies of hydatiform moles and gestational choriocarcinoma].
AB  - The complete hydatidiform mole (CHM), a gestational trophoblastic disease, is
      usually caused by the development of an androgenic egg whose genome is
      exclusively paternal. Due to parental imprinting, only trophoblasts develop in
      the absence of a fetus. CHM are diploid and no abnormal karyotype is observed. It
      is 46,XX in most cases and less frequently 46,XY. The major complication of this
      disease is gestational choriocarcinoma, a metastasizing tumor and a true
      allografted malignancy. This complication is infrequent in developed countries,
      but is more common in the developing countries and is then worsened by delayed
      care. The malignancies are often accompanied by acquired, possibly etiological
      genomic abnormalities. We investigated the presence of recurrent cytogenetic
      abnormalities in CHM and post-molar choriocarcinoma using metaphasic CGH (mCGH)
      and high-resolution 244K aCGH techniques. The 10 CHM studied by mCGH showed no
      chromosomal gains or losses. For post-molar choriocarcinoma, 11 tumors, whose
      diagnosis was verified by histopathology, were investigated by aCGH. Their
      androgenic nature and the absence of tumor DNA contamination by maternal DNA were
      verified by the analysis of microsatellite markers. Three choriocarcinoma cell
      lines (BeWo, JAR and JEG) were also analyzed by aCGH. The results allowed us to
      observe some chromosomal rearrangements in primary tumors, and more in the cell
      lines. Chromosomal abnormalities were confirmed by FISH and functional effect by
      immunohistochemical analysis of gene expression. Forty minimum critical regions
      (MCR) were defined on chromosomes. Candidate genes implicated in choriocarcinoma
      oncogenesis were selected. The presence in the MCR of many miRNA clusters whose
      expression is modulated by parental imprinting has been observed, for example in
      14q32 or in 19q13.4. This suggests that, in gestational choriocarcinoma, the
      consequences of gene abnormalities directly linked to acquired chromosomal
      abnormalities are superimposed upon those of imprinted genes altered at
      fertilization.

PMID- 22877884
TI  - Stem cells in the hood: the skeletal muscle niche.
AB  - It is generally accepted that the principal resident progenitor underlying
      regenerative capacity in skeletal muscle is the satellite cell. Satellite cells
      are present throughout life even though regenerative capacity declines with age
      and disease. Recently, other stem cell populations have been identified that can
      participate in muscle growth and regeneration. These cells may provide
      therapeutically useful sources of muscle stem cells as an alternative to
      satellite cells; however, the roles of these nonsatellite cell populations during
      muscle homeostasis, regeneration, and aging are unclear. Here, we discuss how the
      stem cell neighborhood influences satellite cell behavior and bring together
      recent discoveries pertaining to a wide variety of adult stem cells, including
      muscle stem cells and their niche.

PMID- 22877885
TI  - Early recognition of reverse pseudohyperkalemia in heparin plasma samples during
      leukemic hyperleukocytosis can prevent iatrogenic hypokalemia.
AB  - OBJECTIVES: To investigate the cause of apparent hyperkalemia in leukemic heparin
      plasma. DESIGN AND METHODS: Lithium heparin plasma and serum samples from a
      patient with chronic lymphocytic leukemia (CLL) with hyperleukocytosis were
      transported by either a pneumatic tube system or manual transport and analyzed
      either immediately or after 4 h. RESULTS: Pneumatic tube transported samples
      resulted in higher plasma potassium levels than manually transported samples.
      Serum potassium was lower than plasma potassium, confirming the suspicion of
      "reverse" pseudohyperkalemia. Letting the pneumatic tube transported samples
      stand on the bench for 4 h before centrifugation surprisingly resulted in
      decreased or unchanged plasma potassium. CONCLUSIONS: The reverse
      pseudohyperkalemia in heparin plasma samples from a CLL patient was caused by
      pneumatic tube transport. Our results suggest extracellular leakage of potassium,
      followed by active transport of potassium into intact leukemic cells. This is the
      first Swedish case of reverse pseudohyperkalemia in a CLL patient, where clinical
      suspicion of false hyperkalemia and awareness of the phenomenon lead to a rapid
      laboratory diagnosis. The demonstration of reverse pseudohyperkalemia prevented
      potentially dangerous medical interventions, such as potassium lowering
      treatment.

PMID- 22877886
TI  - Characterization of the mucocutaneous junction of the human eyelid margin and
      meibomian glands with different biomarkers.
AB  - PURPOSE: To investigate the morphology of the human eyelid margin and the
      presence of different cytokeratins, mucins and stem cell markers within the skin
      epithelium, mucocutaneous junction (MCJ) and palpebral conjunctiva. METHODS:
      Eyelids of body donors were investigated histologically and ultrastructurally as
      well as by immunohistochemical methods using antibodies to cytokeratins 1, 4, 7,
      8, 10, 13, 14, 15, and 19; mucins MUC1, MUC4, and MUC5AC and potential stem cell
      markers K15, BCRP/ABCG2, integrin beta1, and N-cadherin. RESULTS: The expression
      pattern of cytokeratins, mucins and stem cell markers varied across the different
      epithelia of the human eyelid. Within the MCJ, CK7, 15 and 19 were absent,
      whereas the epithelium reacted positive to antibodies to CK1, 4, 8, 10, 13 and
      14. Reactivity was also observed for MUC1 and MUC4, but not for MUC5AC. No
      reactivity was determined for K15, BCRP/ABCG2 and integrin beta1 in the area of
      the MCJ epithelium but a strong reactivity was present for N-cadherin.
      CONCLUSIONS: The present immunohistochemical findings lead to a better
      characterization of the MCJ. Additionally, the knowledge of distribution of
      biomarkers like cytokeratins, mucins and stem cells can be useful in the
      investigation of MCJ disturbances which occur in several disorders of the
      meibomian glands and the lid epithelium in the course of dry eye syndrome and
      especially meibomian gland dysfunction.

PMID- 22877887
TI  - Effect of maternal low protein diet during pregnancy on the fetal liver of rats.
AB  - Maternal protein restriction plays a critical role in the developmental
      programming of later disease susceptibility of the fetus. Developmental insults
      could exert permanent effects on health through alteration of tissue morphology.
      As the liver has the greatest number of functions among other body organs, this
      study aimed at evaluating the effects of maternal dietary protein insufficiency
      on the structure and the proliferative capacity of the liver in rat fetuses.
      Morphometric histological studies and biochemical analysis were performed. Twenty
      adult Albino female Wistar rats were divided into two groups after confirmation
      of pregnancy. Group I (ST), serving as control, was fed a standard diet (20%
      protein) and group II (LP) a low protein diet (5% protein). Fetuses were
      extracted on the day 21.5 of pregnancy. Group II morphometric results revealed a
      significant decrease in the mothers' weight gain, number and weight of fetuses
      and weight of fetal livers, but there was also an increase in the mean area of
      hepatocytes. Histological results showed apoptosis, vacuolization of the
      hepatocytes, increased positivity of the Oil Red O stained fat droplets and the
      PAS-positive stained glycogen granules. Liver TUNEL showed increased apoptotic
      nuclei. Ki-67 immunostaining showed decreased proliferation of the hepatocytes.
      Ultrastructurally, the nucleus showed peripheral masses of heterochromatin
      besides irregular nuclear and cell membranes. Mitochondria varied in shape with
      loss of cristea. Biochemically, there was a significant decrease in the protein
      concentration and a significant increase in the glycogen concentration in livers
      of group II. It thus appears that the maternal metabolic condition not only
      reduced fetal growth in response to protein restriction, but also altered the
      structure of the liver.

PMID- 22877888
TI  - Visceral sensitivity as a mediator of outcome in the treatment of irritable bowel
      syndrome.
AB  - Patients with irritable bowel syndrome (IBS) experience anxiety about visceral
      sensations, leading to avoidance behaviors and hypervigilance that maintain IBS
      symptoms. The current study used data from a clinical trial that compared a
      treatment aimed at reducing anxiety about visceral sensations (interoceptive
      exposure; IE) to an attention control (AC) and a CBT-based stress-management
      treatment (SM) to examine whether changes in visceral sensitivity mediated IBS
      symptom and quality of life outcomes. Data from participants who completed one of
      the three treatments (N = 76) were subjected to mediation analyses. Visceral
      sensitivity mediated treatment outcomes across all outcome measures and across
      all treatment groups, with no differences between IE and the other treatment
      groups. This finding suggests that psychosocial treatments for IBS may work by
      decreasing visceral sensitivity, and the degree to which visceral sensitivity is
      decreased is related to outcome, suggesting IE may be the preferable treatment
      option.

PMID- 22877889
TI  - A systematic review of screening tools for predicting the development of
      dementia.
AB  - Early detection of dementia is essential to guide front-line health care
      practitioners in further clinical evaluations and treatments. There is a paucity
      of literature assessing the effectiveness of screening tools to predict the
      development of dementia, thus we conducted a systematic review to fill this gap.
      The purpose of the systematic review was to make recommendations to health care
      practitioners on which screening tool best predicts the development of dementia
      and is most feasible in the primary care setting. Ten databases were searched for
      relevant articles, yielding 751 papers. Of these, 12 met relevance criteria for
      inclusion. Screening tools were assessed for test accuracy, cognitive domain
      coverage, predictive ability, and feasibility. Four screening tools were
      recommended. Addenbrooke's Cognitive Examination (ACE) was considered to be the
      ideal tool. A revised version of this tool is now used in clinical practice but
      the psychometric properties of the ACE-R remain to be established.

PMID- 22877890
TI  - Multiple pregnancies following deep inferior epigastric perforator (DIEP) flap
      breast reconstruction.
AB  - Pregnancy following abdominal flap-based breast reconstruction may cause stress
      to the abdominal wall. These changes may result in weakness and hernia or bulge.
      We present two patients who previously underwent unilateral deep inferior
      epigastric perforator (DIEP) flap breast reconstruction and became pregnant
      twice. Both patients maintained abdominal contour without bulges or hernias.
      Subjectively, patients reported minor changes to abdominal strength. Therefore,
      these two patients had minimal abdominal morbidity following pregnancy after
      unilateral DIEP flap reconstruction.

PMID- 22877891
TI  - Assessment of long term function following hypospadias reconstruction: do flow
      rates, flow quality and cosmesis improve with time? Results from the modified
      Bretteville technique.
AB  - BACKGROUND: Very few studies on long term evaluation of functional outcome
      following hypospadias reconstruction are available. Results from the modified
      Bretteville method have shown excellent cosmesis with a low risk of fistula and
      stenosis. This study addresses the question; do flow rates, quality of urinary
      stream and cosmesis change over time? METHODS: A sample of 18 patients who had
      undergone the 2 stage modified Bretteville technique between 1998 and 2004 were
      reviewed. Following a mean interval of 10 years and 5 months from initial
      functional assessment, repeat evaluation was performed using the "HOSE"
      questionnaire, flowmetry, and spray analysis. RESULTS: Improvement in mean flow
      rate (15.3 vs 10.1 ml/s; p value = 0.0036), reduced spraying (3.2 g vs 4.4 g; p
      value = 0.2927), with a mean increase in the "HOSE" score (from 13.8 (maximum
      score 16) to 15.4 (maximum score 16); p value = 0.0440) was observed over the
      follow up time. CONCLUSION: Improvement in flow rates, flow quality, and cosmesis
      over a mean interval of 10 years 5 months has been demonstrated in a random
      cohort of patients undergoing the modified Bretteville method of hypospadias
      reconstruction.

PMID- 22877892
TI  - Identifying factors related to Achilles tendon stress, strain, and stiffness
      before and after 6 months of growth in youth 10-14 years of age.
AB  - The purposes of this study were (1) determine if youth peak Achilles tendon (AT)
      strain, peak AT stress, and AT stiffness, measured during an isometric plantar
      flexion, differed after six months (mos) of growth, and (2) determine if sex,
      physical activity level (Physical Activity Questionnaire (PAQ-C)), and/or growth
      rate (GR) were related to these properties. AT stress, strain, and stiffness were
      quantified in 20 boys (13.47+/-0.81 years) and 22 girls (11.18+/-0.82 years) at 2
      times (0 and 6 mos). GR (change in height in 6 mos) was not significantly
      different between boys and girls (3.5+/-1.4 and 3.4+/-1.1cm/6 mos respectively).
      Peak AT strain and stiffness (mean 3.8+/-0.4% and 128.9+/-153.6N/mm,
      respectively) did not differ between testing sessions or sex. Peak AT stress
      (22.1+/-2.4 and 24.0+/-2.1MPa at 0 and 6 mos, respectively) did not differ
      between sex and increased significantly at 6 mos due to a significant decrease in
      AT cross-sectional area (40.6+/-1.3 and 38.1+/-1.6mm(2) at 0 and 6 mos,
      respectively) with no significant difference in peak AT force (882.3+/-93.9 and
      900.3+/- 65.5N at 0 and 6 mos, respectively). Peak AT stress was significantly
      greater in subjects with greater PAQ-C scores (9.1% increase with 1 unit increase
      in PAQ-C score) and smaller in subjects with faster GRs (13.8% decrease with
      1cm/6 mos increase in GR). These results indicate that of the AT mechanical
      properties quantified, none differed between sex, and only peak AT stress
      significantly differed after 6 months and was related to GR and physical
      activity.

PMID- 22877893
TI  - A behavioral genetic study of humor styles in an Australian sample.
AB  - The present study investigated the extent to which individual differences in
      humor styles are attributable to genetic and/or environmental factors in an
      Australian sample. Participants were 934 same-sex pairs of adult twins from the
      Australian Twin Registry (546 monozygotic pairs, 388 dizygotic pairs) who
      completed the Humor Styles Questionnaire (HSQ). The HSQ measures four distinct
      styles of humor - affiliative, self-enhancing, aggressive, and self-defeating.
      Results revealed that additive genetic and non-shared environmental factors
      accounted for the variance in all four humor styles, thus replicating results
      previously obtained in a sample of twins from the United Kingdom. However, a
      study conducted with a U.S. sample produced different results and we interpret
      these findings in terms of cross-cultural differences in humor.

PMID- 22877894
TI  - An unusual cause of headache and hypertension.
AB  - Children with both headache and hypertension present a relatively rare condition
      with a broad range of differential diagnoses in pediatric emergency medicine.
      Some possible diagnoses are potentially life-threatening conditions and merit
      aggressive evaluation management. We report a case of a 14-year-old girl who
      presented with headache and hypertension. She responded poorly to medical
      treatment and subsequently developed anxiety and difficulties with concentration.
      Three months later, she visited our ophthalmology department because of blurred
      vision. Ophthalmic evaluation revealed bilateral Kayser-Fleischer rings. Finally,
      she was diagnosed with Wilson disease. This case emphasizes that children with
      headache and hypertension merit aggressive evaluation and management.

PMID- 22877895
TI  - Association of aortic flow propagation velocity with ankle-brachial blood
      pressure index in patients with hypertension: an observational study.
AB  - OBJECTIVE: Endothelial dysfunction is considered the first stage in the
      development of atherosclerosis and assessed by flow-mediated dilatation (FMD) and
      aortic flow velocity propagation (AVP). Ankle-brachial index (ABI) is used to
      assess peripheral arterial disease and is associated with FMD but the
      relationship between ABI and AVP is unknown. In this study, we aimed to search
      the association between AVP, and ABI in patients with newly diagnosed
      hypertension. METHODS: Sixty-eight patients with newly diagnosed hypertension and
      34 healthy subjects were enrolled in the cross-sectional observational study. The
      maximum ankle arterial pressures were divided by the maximum of the brachial
      arterial pressures to calculate the ABI. AVP was calculated from dividing the
      distance between points corresponding to the beginning and end of the propagation
      slope, to the duration between corresponding time points proximally descending
      aorta. Statistical analysis was performed using Student t-test, Chi-square test,
      Pearson correlation and linear regression analyses. RESULTS: Age and gender of
      both groups were similar. Compared to control group E deceleration time of early
      diastolic flow velocity (184.0+/-32.2 vs. 217.1+/-38.6, p<0.001), isovolumic
      relaxation time (95.5+/-19.4 vs. 105.7+/-18.1, p<0.001) and body mass index
      (25.6+/-5.1 vs. 27.5+/-3.8, p=0.044) values were significantly higher, while ABI
      (1.08+/-0.07 vs. 1.14+/-0.07, p=0.001) and AVP (54.97+/-9.3 vs. 69.17+/-10.8
      cm/sec, p=0.001) values were significantly lower in hypertensive patients. There
      was a significant correlation between AVP and ABI (r=0.279, p=0.005). Both ABI
      and AVP were independent predictors of hypertension (OR - 0.353, 95%CI 0.151
      0.826, p=0.02 and OR - 0.133, 95%CI 0.0502-0.35, p=0.001, respectively).
      CONCLUSION: Our data indicate that in patients with isolated hypertension AVP and
      ABI decrease. We also conclude that AVP is directly associated with ABI.

PMID- 22877896
TI  - Low serum free triiodothyronine levels are associated with the presence and
      severity of coronary artery disease in the euthyroid patients: an observational
      study.
AB  - OBJECTIVE: The aim of this study is to investigate the relationship between serum
      thyroid hormone levels that are within the normal range and the presence and
      severity of coronary artery disease (CAD) in patients referred for coronary
      angiography. METHODS: In this observational study, we enrolled 119 consecutive
      patients (77 men, mean age 60.7+/-13.8 years) who underwent coronary angiography.
      Blood samples were tested for thyroid stimulating hormone (TSH), free
      triiodothyronine (FT3) and free thyroxine (FT4) concentrations. Additionally,
      risk factors, clinical characteristics and angiographic results were obtained.
      The patients were separated into two groups according to the Gensini score as
      those with mild or severe atherosclerosis. Statistical analysis was performed
      using the Chi-square, Mann-Whitney U, correlation and logistic regression tests,
      and ROC analysis. RESULTS: FT3 levels were significantly lower in subjects with
      CAD (4.0+/-0.7 vs. 4.6+/-0.6 pmol/L; p<0.001). Moreover, lower FT3 levels were
      found in patients with severe atherosclerosis (3.9+/-0.7 vs. 4.5+/-0.6 pmol/L;
      p<0.001). Logistic regression analysis demonstrated that the lower FT3 levels
      were associated with the presence (OR =0.266, 95% CI: 0.097-0.731, p=0.01) and
      severity (OR=0.238, 95% CI:0.083-0.685, p=0.008) of CAD. In the ROC analysis, a
      level of FT3 <=4.2 pmol/L was found to predict the presence of CAD with 69%
      sensitivity and 71% specificity (AUC:0.744, 95% CI:0.653-0.834, p<0.001); and the
      severity of CAD with 75% sensitivity and 67% specificity (AUC:0.733, 95% CI:0.642
      0.824, p<0.001). CONCLUSIONS: FT3 levels within the normal range were inversely
      correlated with the presence and severity of CAD. Moreover, lower FT3
      concentrations were correlated with the Gensini score and independently predicted
      the presence and severity of CAD. Thus, the FT3 levels may be used as the
      indicator of increased risk for CAD.

PMID- 22877897
TI  - Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and
      vulnerability to atrial fibrillation in diabetic rabbits.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of
      hyperglycemia on atrial interstitial fibrosis, ionic remodeling and vulnerability
      to atrial fibrillation (AF) in alloxan-induced diabetic rabbits. METHODS: Sixty
      Japanese rabbits were randomly assigned to alloxan-induced diabetic group (n=30)
      and control group (n=30). Ten rabbits in each group were respectively used to
      electrophysiological and histological study, patch-clamp study and Western
      blotting analysis. Langendorff perfusion was used to record inter-atrial
      conduction time (IACT), atrial effective refractory period (AERP) and dispersion
      (AERPD) and vulnerability to AF. Histological study was measured by Sirius-red
      stain. Patch-clamp technique was used to measure action potential duration (APD)
      and atrial ionic currents (INa and ICaL). Western blotting was applied to assess
      atrial protein expression of transforming growth factor beta 1 (TGFbeta1).
      RESULTS: Compared with control group, electrophysiological studies showed IACT
      was prolonged (37.91+/-6.81 vs. 27.43+/-1.63ms, p<0.01), AERPD was increased
      (30.37+/-8.33 vs. 14.70+/-5.16ms, p<0.01) in diabetic group. Inducibility of AF
      in diabetic group was significantly higher than in controls (8/10 vs. 1/10 of
      animals, p<0.01). Collagen volume fraction was increased (6.20+/-0.64% vs. 2.15+/
      0.21%, p<0.01) in diabetic group. Patch-clamp studies demonstrated APD90 and
      APD50 were prolonged in diabetic rabbits (p<0.05 vs. control). The densities of
      INa were reduced and the densities of ICaL were increased (p<0.01 vs. control).
      Protein expression of TGFbeta1 was increased in diabetic group (p<0.001 vs.
      control). CONCLUSION: Our study suggests that hyperglycemia contributes to atrial
      interstitial fibrosis, ionic remodeling and vulnerability to AF in diabetic
      rabbits, resulting in atrial structural remodeling and electrical remodeling for
      the development and perpetuation of AF.

PMID- 22877898
TI  - Hyperglycemia and atrial fibrillation: new clinical information on
      electrophysiological changes.

PMID- 22877899
TI  - New fully automated software for assessment of brachial artery flow- mediated
      dilation with advantages of continuous measurement.
AB  - OBJECTIVE: Flow-mediated dilation (FMD) is used to evaluate endothelial
      functions. Computer-assisted analysis utilizing edge detection permits continuous
      measurements along the vessel wall. We have developed a new fully automated
      software program to allow accurate and reproducible measurement. METHODS: FMD has
      been measured and analyzed in 18 coronary artery disease (CAD) patients and 17
      controls both by manually and by the software developed (computer supported)
      methods. The agreement between methods was  assessed by Bland-Altman analysis.
      RESULTS: The mean age, body mass index and cardiovascular risk factors were
      higher in CAD group. Automated FMD% measurement for the control subjects was
      18.3+/-8.5 and 6.8+/-6.5 for the CAD group (p=0.0001). The intraobserver and
      interobserver correlation for automated measurement was high (r=0.974, r=0.981,
      r=0.937, r=0.918, respectively). Manual FMD% at 60th second was correlated with
      automated FMD % (r=0.471, p=0.004). CONCLUSIONS: The new fully automated
      software(c) can be used to precise measurement of FMD with low intra- and
      interobserver variability than manual assessment.

PMID- 22877900
TI  - A case of Kounis syndrome presented with sudden cardiac death.

PMID- 22877901
TI  - Refractory hemolytic anemia due to severe swirling flow pattern in chronic mitral
      regurgitation after myxoma surgery.

PMID- 22877902
TI  - [Implantation of cardioverter-defibrillator and cardiac resynchronization device
      in a patient with preserved right ventricular lead after tricuspid valve
      surgery].

PMID- 22877903
TI  - Unilateral pulmonary artery agenesis: clinical and laboratory findings of four
      cases and diagnostic clues for pediatricians.

PMID- 22877905
TI  - Complete heart block and permanent pacemaker implantation in a patient with
      systemic sclerosis.

PMID- 22877904
TI  - Traumatic pulmonary valve hematoma; an unusual complication of pulmonary balloon
      valvuloplasty.

PMID- 22877906
TI  - [Sturge-Weber syndrome and dilated cardiomyopathy: coincidence or associated
      disease?].

PMID- 22877907
TI  - Does intermediate high-altitude level affect major cardiovascular outcomes of
      patients with acute myocardial infarction treated by primary coronary
      angioplasty? Preliminary results of observational study.

PMID- 22877908
TI  - Delirium due to contrast toxicity after coronary angioplasty.

PMID- 22877909
TI  - Clinical analysis of neonates with congenital heart disease in the neonatal
      intensive care unit: a 5-year experience.

PMID- 22877910
TI  - Intracoronary shunt use in an adult patient with Bland-White-Garland syndrome.

PMID- 22877911
TI  - Successful management of an unwanted complication; VAC therapy.

PMID- 22877912
TI  - Unexpected complication- fracture of the IVUS catheter and percutaneous retrieval
      of a broken IVUS catheter tip from the right coronary artery.

PMID- 22877913
TI  - Acute myocardial infarction secondary to blunt chest trauma treated with thrombus
      aspiration.

PMID- 22877914
TI  - A closer sight to the transapical cardiac resynchronization therapy.

PMID- 22877915
TI  - Melting heart: dilated phase of hypertrophic cardiomyopathy.

PMID- 22877916
TI  - Huge aortic vegetation embolizing to right iliac artery.

PMID- 22877917
TI  - A rare interventricular mass like view-fibrosis.

PMID- 22877918
TI  - Persistent left superior vena cava associated with giant coronary sinus.

PMID- 22877919
TI  - The 9th International Scientific Summer School 2012 in Makov, Slovakia.

PMID- 22877921
TI  - Can food and addiction change the game?

PMID- 22877922
TI  - Association of stroke with the receptor-binding profiles of antipsychotics-a case
      crossover study.
AB  - BACKGROUND: Previous research suggests a link between antipsychotic use and
      stroke, but the relationships between receptor-binding profiles of antipsychotics
      and the risk of cerebrovascular events are unclear. METHODS: A total of 14,584
      patients with incident stroke were enrolled in the National Health Insurance
      Research Database in Taiwan from 1998 to 2007. We conducted a case-crossover
      study to compare the rates of antipsychotic use. The effects of receptor-binding
      profiles of antipsychotics on stroke risk were estimated, while the moderating
      effects of age, sex, presence of dementia, and duration of antipsychotic
      treatment were evaluated by stratified analyses. RESULTS: The adjusted odds ratio
      of stroke risk with antipsychotics exposure was 1.60 (95% confidence interval,
      1.51-1.69) using a 14-day time window. The use of antipsychotics with a high
      binding affinity of M1 muscarinic and alpha2 adrenergic receptors was associated
      with a greater risk of stroke than the use of other types of antipsychotics. An
      increased risk of stroke with antipsychotic use was noted in the patients who
      were older and/or who suffered from dementia. Moreover, our results showed that
      stroke risk with antipsychotic use was in a dose-related relationship.
      CONCLUSIONS: Our findings suggest an association between stroke risk and high M1
      muscarinic and alpha2 adrenergic affinity. The clinical implication is to start
      antipsychotics treatment at low dosages and to closely monitor the side effects
      in the initial treatment, particularly for individuals with older age and the
      presence of dementia.

PMID- 22877923
TI  - Is D-cycloserine a prodrug for D-serine in the brain?

PMID- 22877924
TI  - Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder.
AB  - OBJECTIVES: Bipolar disorder is a severe mental disorder with prominent genetic
      etiologic factors. Dopaminergic dysfunction has been implicated in the
      pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor
      gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor
      (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined
      the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two
      subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3
      expression (1), we also examined possible interactions between these genes.
      METHODS: We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II,
      and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly
      polymorphisms were determined using polymerase chain reactions plus restriction
      fragment length polymorphism analysis. RESULTS: Logistic regression analysis
      showed a significant main effect for the Val/Val genotype of the BDNF Val66Met
      polymorphism (P=0.020), which predicted bipolar-II patients. Significant
      interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly
      Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P=0.027 and
      0.006, respectively). CONCLUSION: We provide initial evidence that the BDNF
      Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that
      bipolar-I and bipolar-II may be genetically distinct.

PMID- 22877925
TI  - Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted
      anticancer chemotherapy.
AB  - As a further extension of our research work focusing on the development of
      gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential
      anticancer agents, complexes [Au(III)X(2)(dtc-Sar-L-Ser(t-Bu)-O(t-Bu))] (X=Br
      (1a)/Cl (1b)), [Au(III)X(2)(dtc-AA-Aib(2)-O(t-Bu))] (AA=Sar (sarcosine, N
      methylglycine), X=Br (2a)/Cl (2b); AA=D,L-Pro, X=Br (3a)/Cl (3b)),
      [Au(III)X(2)(dtc-Sar-Aib(3)-O(t-Bu))] (X=Br (4a)/Cl (4b)), and [Au(III)X(2)(dtc
      Sar-Aib(3)-Gly-OEt)] (X=Br (5a)/Cl (5b)) (Aib = "alpha"-aminoisobutyric acid, 2
      methylalanine) were designed to obtain metal-based peptidomimetics that may
      specifically target two peptide transporters (namely, PEPT1 and PEPT2)
      upregulated in several human tumor cells. All the compounds were characterized by
      means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in
      vitro cytotoxicity studies, complex [Au(III)Cl(2)(dtc-D,L-Pro-Aib(2)-O(t-Bu))]
      (3b) turned out to be the most effective toward the four human tumor cell lines
      evaluated (PC3, 2008, C13, and L540), for which the IC(50) values were lower than
      cisplatin. Remarkably, it showed no cross-resistance with cisplatin itself and
      was proved to inhibit tumor cell proliferation by inducing almost exclusively
      late apoptosis/necrosis. Biological results are here reported and discussed in
      terms of the structure-activity relationship.

PMID- 22877926
TI  - What do we know about the reduction of Pt(IV) pro-drugs?
AB  - Platinum(IV) pro-drugs are an important class of molecules that might improve the
      pharmacological properties of the platinum(II) anticancer agents that are
      currently used in the clinic. Their axial ligands that are detached during
      cellular activation by reductive elimination can be used to confer favorable
      pharmacological properties to the complexes allowing for potentially lower
      toxicity and improved efficacy. This manuscript describes the various approaches
      taken to design and prepare Pt(IV) complexes that will be effective anticancer
      agents. We review the working hypotheses guiding the researchers in the field
      while pointing out some more recent results that contradict some of the accepted
      paradigms in the hope of triggering some rethinking of the existing working
      hypotheses.

PMID- 22877927
TI  - [RuII(eta5-C5H5)(bipy)(PPh3)]+, a promising large spectrum antitumor agent:
      cytotoxic activity and interaction with human serum albumin.
AB  - Ruthenium complexes hold great potential as alternatives to cisplatin in cancer
      chemotherapy. We present results on the in vitro antitumor activity of an
      organometallic 'Ru(II)Cp' complex, [Ru(II)Cp(bipy)(PPh(3))][CF(3)SO(3)],
      designated as TM34 (PPh(3) = triphenylphosphine; bipy = 2,2'-bipyridine), against
      a panel of human tumor cell lines with different responses to cisplatin
      treatment, namely ovarian (A2780/A2780cisR, cisplatin sensitive and resistant,
      respectively), breast (MCF7) and prostate (PC3) adenocarcinomas. TM34 is very
      active against all tumorigenic cell lines, its efficacy largely surpassing that
      of cisplatin (CisPt). The high activity of TM34 towards CisPt resistant cell
      lines possibly suggests a mechanism of action distinct from that of CisPt. The
      effect of TM34 on the activity of the enzyme poly(ADP-ribose) polymerase 1 (PARP
      1) involved in DNA repair mechanisms and apoptotic pathways was also evaluated,
      and it was found to be a strong PARP-1 ruthenium inhibitor in the low micromolar
      range (IC(50)=1.0 +/- 0.3 MUM). TM34 quickly binds to human serum albumin forming
      a 1:1 complex with a conditional stability constant (log K'~4.0), comparable to
      that of the Ru(III) complex in clinical trial KP1019. This indicates that TM34
      can be efficiently transported by this protein, possibly being involved in its
      distribution and delivery if the complex is introduced in the blood stream.
      Albumin binding does not affect TM34 activity, yielding an adduct that maintains
      cytotoxic properties (against A2780 and A2780cisR cells). Altogether, the
      properties herein evaluated suggest that TM34 could be an anticancer agent of
      highly relevant therapeutic value.

PMID- 22877928
TI  - Anti-mycobacterial natural products from the Canadian medicinal plant Juniperus
      communis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Common juniper, Juniperus communis, is amongst
      the plants most frequently used by the indigenous peoples of North America for
      medicinal purposes. The First Nations of the Canadian Maritimes use infusions of
      juniper primarily as a tonic and for the treatment of tuberculosis. Previous
      investigations of extracts derived from the aerial parts of J. communis have
      shown it to possess anti-mycobacterial activity. The aim of the study is to
      isolate and identify anti-mycobacterial constituents from the aerial parts of J.
      communis. MATERIALS AND METHODS: Methanolic extracts of J. communis needles and
      branches were subjected to bioassay guided fractionation using the microplate
      resazurin assay (MRA) to assess inhibitory activity against Mycobacterium
      tuberculosis strain H37Ra. The anti-mycobacterial constituents were identified by
      NMR, MS and polarimetry. RESULTS: The diterpenes isocupressic acid and communic
      acid and the aryltetralin lignan deoxypodophyllotoxin were isolated from the J.
      communis extract. Isocupressic acid and communic acid (isolated as an inseparable
      3:2 mixture of cis and trans isomers) displayed MICs of 78 MUM and 31 MUM and
      IC(50)s of 46 MUM and 15 MUM against M. tuberculosis H37Ra respectively.
      Deoxypodophyllotoxin was less active, with a MIC of 1004 MUM and an IC(50) of 287
      MUM. CONCLUSIONS: Isocupressic acid, communic acid and deoxypodophyllotoxin were
      identified as the principal constituents responsible for the anti-mycobacterial
      activity of the aerial parts of J. communis. Although further research will be
      required to evaluate the relative activities of the two communic acid isomers,
      this work validates an ethnopharmacological use of this plant by Canadian First
      Nations and Native American communities.

PMID- 22877930
TI  - Gender and geographic differences in the prevalence of intellectual disability in
      children: analysis of data from the national disability registry of Taiwan.
AB  - Intellectual disability (ID) is not uncommon in children, but data at the
      national level are limited, especially those on geographic differences. On the
      basis of the Disabled Welfare Law, Taiwan began to certify disabled residents and
      provide various services in 1980. All the cases are registered, and the registry
      provides a rare opportunity for studying ID at the national level. Using the data
      from 2004 to 2010, we calculated the prevalence of ID in children by age, gender,
      and geographic area and assessed the changes over time. We limited analyses to
      children at least 3 years of age, because certification before 3 years old is
      discouraged by the government. We found that from 2004 to 2010, the registered
      cases between 3 and 17 years old ranged from 20,531 to 23,547, and the prevalence
      of ID increased constantly from 4.40/1000 to 5.79/1000 (p<0.01), which generally
      increased every year in all age groups (p<0.01). In each year there were more boy
      cases than girl cases, and the boy-to-girl ratio generally decreased with age
      (p<0.01 for chi-square test for trend in all years). The prevalence rate ratio
      ranged from 1.33 to 1.37 (p<0.01 in all years), and the changes in the rate ratio
      were small over the years. We observed a higher prevalence in the rural areas
      over the years, and the prevalence rate ratio ranged from 1.34 to 1.43 (p<0.01 in
      all years), with an increasing trend over time (p<0.01).

PMID- 22877931
TI  - The migration decisions of physicians in Canada: the roles of immigrant status
      and spousal characteristics.
AB  - Around 25% of practicing physicians in Canada are graduates of medical schools
      outside of Canada. These physicians are more likely to be working in rural
      communities, and in particular account for more than half of new physicians
      starting practice in rural regions. The extent to which particular health regions
      and provinces are able to retain their physicians is crucial if shortages in the
      delivery of physician and surgeon services in both the short and longer terms are
      to be avoided. In this paper, we use data from the confidential master files of
      the Canadian Census over the years 1991-2006 to study the geographic mobility of
      immigrant and non-immigrant physicians who are already resident in Canada. We
      consider both inter- and intra-provincial migration, with a particular focus on
      migration to and from rural areas of Canada. We exploit the fact that it is
      possible to link individuals within families in the Census files in order to
      investigate the impact on the migration decision of the characteristics of a
      married physician's spouse. Our results indicate that the magnitude of outflows
      is substantial and that the retention of immigrant physicians in rural areas and
      in some provinces will continue to be difficult. We find strong evidence that
      migration is a family decision, and spousal characteristics (education, age,
      years in Canada for immigrants) are important. As well, we find that large
      Canadian cities (mainly in Ontario) are the likely destination for the types of
      immigrant physicians typically able to be recruited to other areas, implying
      recruitment efforts of smaller provinces may have significant implications for
      the size of health care costs in larger provinces.

PMID- 22877929
TI  - The Vanderbilt Expertise Test reveals domain-general and domain-specific sex
      effects in object recognition.
AB  - Individual differences in face recognition are often contrasted with differences
      in object recognition using a single object category. Likewise, individual
      differences in perceptual expertise for a given object domain have typically been
      measured relative to only a single category baseline. In Experiment 1, we present
      a new test of object recognition, the Vanderbilt Expertise Test (VET), which is
      comparable in methods to the Cambridge Face Memory Task (CFMT) but uses eight
      different object categories. Principal component analysis reveals that the
      underlying structure of the VET can be largely explained by two independent
      factors, which demonstrate good reliability and capture interesting sex
      differences inherent in the VET structure. In Experiment 2, we show how the VET
      can be used to separate domain-specific from domain-general contributions to a
      standard measure of perceptual expertise. While domain-specific contributions are
      found for car matching for both men and women and for plane matching in men,
      women in this sample appear to use more domain-general strategies to match
      planes. In Experiment 3, we use the VET to demonstrate that holistic processing
      of faces predicts face recognition independently of general object recognition
      ability, which has a sex-specific contribution to face recognition. Overall, the
      results suggest that the VET is a reliable and valid measure of object
      recognition abilities and can measure both domain-general skills and domain
      specific expertise, which were both found to depend on the sex of observers.

PMID- 22877932
TI  - Ethics and images of suffering bodies in humanitarian medicine.
AB  - Media representations of suffering bodies from medical humanitarian organisations
      raise ethical questions, which deserve critical attention for at least three
      reasons. Firstly, there is a normative vacuum at the intersection of medical
      ethics, humanitarian ethics and the ethics of photojournalism. Secondly, the
      perpetuation of stereotypes of illness, famine or disasters, and their political
      derivations are a source of moral criticism, to which humanitarian medicine is
      not immune. Thirdly, accidental encounters between members of the health
      professions and members of the press in the humanitarian arena can result in
      misunderstandings and moral tension. From an ethics perspective the problem can
      be specified and better understood through two successive stages of reasoning.
      Firstly, by applying criteria of medical ethics to the concrete example of an
      advertising poster from a medical humanitarian organisation, I observe that media
      representations of suffering bodies would generally not meet ethical standards
      commonly applied in medical practice. Secondly, I try to identify what overriding
      humanitarian imperatives could outweigh such reservations. The possibility of
      action and the expression of moral outrage are two relevant humanitarian values
      which can further be spelt out through a semantic analysis of 'temoignage'
      (testimony). While the exact balance between the opposing sets of considerations
      (medical ethics and humanitarian perspectives) is difficult to appraise,
      awareness of all values at stake is an important initial standpoint for ethical
      deliberations of media representations of suffering bodies. Future pragmatic
      approaches to the issue should include: exploring ethical values endorsed by
      photojournalism, questioning current social norms about the display of suffering,
      collecting empirical data from past or potential victims of disasters in diverse
      cultural settings, and developing new canons with more creative or less
      problematic representations of suffering bodies than the currently accepted
      stereotypes. 

PMID- 22877933
TI  - A typology of structural approaches to HIV prevention: a commentary on Roberts
      and Matthews.
AB  - Renewed enthusiasm for biomedical HIV prevention strategies has followed the
      recent publication of several high-profile HIV antiretroviral therapy-based HIV
      prevention trials. In a recent article, Roberts and Matthews (2012) accurately
      note some of the shortcomings of these individually targeted approaches to HIV
      prevention and advocate for increased emphasis on structural interventions that
      have more fundamental effects on the population distribution of HIV. However,
      they make some implicit assumptions about the extent to which structural
      interventions are user-independent and more sustainable than biomedical or
      behavioral interventions. In this article, I elaborate a simple typology of
      structural interventions along these two axes and suggest that they may be
      neither user-independent nor sustainable and therefore subject to the same
      sustainability concerns, costs, and potential unintended consequences as
      biomedical and behavioral interventions.

PMID- 22877934
TI  - Condoms "contain worms" and "cause HIV" in Tanzania: Negative Condom Beliefs
      Scale development and implications for HIV prevention.
AB  - Condom promotion remains a key component of HIV prevention programs,
      complimenting recent successes in biomedical HIV prevention. Although condom use
      has increased in much of East Africa, it remains substantially below optimal
      levels. Negative rumors about condoms have been documented in East Africa, yet
      the prevalence and effects of belief in the negative rumors have not been
      explored. This study evaluated levels of belief in negative rumors about condoms,
      developed a Negative Condom Beliefs Scale, and assessed its accuracy in
      predicting willingness to use condoms. A cross-sectional, cluster survey (n =
      370) was conducted representing adults in two rural districts in Northern
      Tanzania in 2008. Item agreement ranged from 35 to 53% for the following rumors
      regarding condoms: causing cancer, having holes, containing HIV, having worms,
      and the worms causing HIV. Items loaded on a single latent factor and had high
      internal consistency and convergent validity. In a multivariate model, negative
      condom score (AOR = 0.67, 95% CI = 0.6, 0.8) was the strongest single predictor
      of willingness to use condoms, followed by greater perceived anonymity in
      acquiring condoms (AOR = 4.36, 95% CI = 2.2, 8.6) and higher condom self-efficacy
      (AOR = 4.24, 95% CI = 2.0, 8.9). Our findings indicate high levels of
      subscription to negative beliefs about condoms, with two out of three respondents
      affirming belief in at least one negative condom rumor. This study highlights the
      relation between condom rumor beliefs and willingness to use condoms, and
      indicates avenues for future research and means for improving the design of HIV
      prevention programs.

PMID- 22877935
TI  - Oxidation of SCN- with air and micellar polyoxoperoxometalates.
AB  - The nanocatalysts were fabricated by reacting amphiphilic quaternary ammoniums
      with polyoxoperoxometalates (POPMs) K(n)[PW(12-)(x)Ti(x)O(40-)(x)(O(2))(x)](x=1,
      2 and 3; n=5, 7 and 9). Fourier transform infrared spectroscopy (IR),
      transmission electron microscopy (TEM), and UV-vis-NIR spectrophotometer were
      used to characterize the resulting samples. This kind of nanocatalysts could
      provide a kind of nanoreactors to promote the degradation of NH(4)SCN into simple
      inorganic compounds such as SO(4)(2-), HCO(3)(-) and NO(3)(-) using oxygen as an
      oxidant under room conditions. The leaching test showed that the POPMs micellar
      catalyst had excellent stability and could be used as a heterogeneous one at
      least five times.

PMID- 22877936
TI  - Removal of tetrabromobisphenol A by conventional activated sludge, submerged
      membrane and membrane aerated biofilm reactors.
AB  - The goal of this study was to compare removal efficiencies of tetrabromobisphenol
      A (TBBPA) using typical wastewater treatment technologies, and to identify the
      most significant mechanisms of removal. Two types of municipal wastewater
      reactors were studied: a full-scale conventional activated sludge (CAS) reactor
      with tertiary treatment; and three pilot-scale membrane bioreactors (MBRs) having
      different sludge retention times (SRTs). All four reactors were fed the same
      influent. A third reactor type, a membrane aerated biofilm reactor (MABR) was fed
      tap water, ammonia, and TBBPA. TBBPA in municipal influent ranged from 1 to 41 ng
      L(-1) (n=10). The CAS effluent had an average TBBPA concentration of 0.7 +/- 1.3
      ng L(-1) (n=3). Effluent concentrations from the MBRs were an average of 6 +/- 6
      ng L(-1) TBBPA (n=26). Significant TBBPA removal was observed in the MABR
      throughout the 5 week of study (p>=0.05). Removal of TBBPA from wastewater
      treatment was found to be due to a combination of adsorption and biological
      degradation. Based on experimental results, nitrification is likely a key process
      therein. No significant relationship between removal of TBBPA and SRT was
      identified (p>=0.05).

PMID- 22877937
TI  - Distinct influence of filter strips on acute and chronic pesticide aquatic
      environmental exposure assessments across U.S. EPA scenarios.
AB  - Vegetative filter strips (VFS) are proposed for protection of receiving water
      bodies and aquatic organisms from pesticides in runoff, but there is debate
      regarding the efficiency and filter size requirements. This debate is largely due
      to the belief that no quantitative methodology exists for predicting runoff
      buffer efficiency when conducting acute and/or chronic environmental exposure
      assessments. Previous research has proposed a modeling approach that links the
      U.S. Environmental Protection Agency's (EPA's) PRZM/EXAMS with a well-tested
      process-based model for VFS (VFSMOD). In this research, we apply the modeling
      framework to determine (1) the most important input factors for quantifying mass
      reductions of pesticides by VFS in aquatic exposure assessments relative to three
      distinct U.S. EPA scenarios encompassing a wide range of conditions; (2) the
      expected range in percent reductions in acute and chronic estimated environmental
      concentrations (EECs); and (3) the differential influence of VFS when conducting
      acute versus chronic exposure assessments. This research utilized three, 30-yr
      U.S. EPA scenarios: Illinois corn, California tomato, and Oregon wheat. A global
      sensitivity analysis (GSA) method identified the most important input factors
      based on discrete uniform probability distributions for five input factors: VFS
      length (VL), organic-carbon sorption coefficient (K(oc)), half-lives in both
      water and soil phases, and application timing. For percent reductions in acute
      and chronic EECs, VL and application timing were consistently the most important
      input factors independent of EPA scenario. The potential ranges in acute and
      chronic EECs varied as a function of EPA scenario and application timing.
      Reductions in acute EECs were typically less than percent reductions in chronic
      EECs because acute exposure was driven primarily by large individual rainfall and
      runon events. Importantly, generic specification of VFS design characteristics
      equal across scenarios should be avoided. The revised pesticide assessment
      modeling framework offers the ability to elucidate the complex and non-linear
      relationships that can inform targeted VFS design specifications.

PMID- 22877938
TI  - The uses and abuses of bibliometrics.

PMID- 22877940
TI  - Fibroblast growth factor 10 in human ovaries.
AB  - The expression of fibroblast growth factor 10 (FGF-10) has not been studied in
      human ovarian cortical follicles. The aim of the present study was to investigate
      the expression of FGF-10 in preantral follicles from fetuses, girls and women.
      Ovarian samples were obtained from 14 human fetuses at 21-33 gestational weeks
      and from 35 girls and women aged 5-39 years. The specimens were prepared for
      detection of the FGF-10 protein by immunohistochemistry. Reverse-transcription
      PCR was applied to ovarian extracts to identify FGF-10 mRNA transcripts. In fetal
      tissue, the FGF-10 protein was detected in oocytes in 50% of the samples and in
      granulosa cells in 30%. In ovarian tissue from girls and women, the FGF-10
      protein was detected in oocytes and granulosa cells in all samples. FGF-10 mRNA
      transcripts were present in all adult and fetal samples tested. The
      identification of FGF-10 at both the protein and mRNA levels suggests that FGF-10
      may contribute to human preantral follicle development.

PMID- 22877941
TI  - Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo
      development kinetics.
AB  - During follicular growth, the follicle is exposed to an almost ever-changing
      composition of isoforms of FSH and LH, which causes a number of different and
      divergent biological effects. Through a time-lapse system, embryo kinetics were
      examined following the use of FSH only (recombinant FSH, rFSH) and gonadotrophins
      containing LH activity (human menopausal gonadotrophin, HMG, and FSH+HMG) in
      oocyte donors. No significant differences were seen between the three groups (for
      rFSH, HMG and rFSH+HMG, t2 was 27.8h, 27.9h and 27.5h respectively). Moreover,
      although embryos obtained with rFSH showed an increase in the proportions of
      optimal timings of development, the differences observed were not significant, as
      shown by the percentages of embryos inside/outside these kinetic variables. In
      contrast, for gonadotrophin dosage and oestradiol concentration, this study
      observed differences in embryo development kinetics for some of the variables
      evaluated, which allowed the description of an optimal range of gonadotrophin
      dosage and oestradiol concentration. However, these kinetic differences did not
      translate into important distinctions in the proportion of optimal embryos with a
      higher implantation potential.

PMID- 22877939
TI  - Altered endometrial expression of endothelial nitric oxide synthase in women with
      unexplained recurrent miscarriage and infertility.
AB  - Endothelial nitric oxide synthase (eNOS) has diverse roles in the female
      reproductive system including a role in blastocyst implantation. Aberrant
      expression of eNOS could therefore be significant in the pathogenesis of
      disorders of implantation. In this study, eNOS protein and mRNA levels in the
      endometrium of women with recurrent miscarriages, unexplained infertility and a
      control group were determined by compartmental quantitative immunohistochemistry
      and real-time reverse-transcription PCR. eNOS was found to be immunolocalized to
      all layers of the endometrium and vascular endothelium. eNOS protein was higher
      in glandular epithelium (P = 0.004) and luminal epithelium (P = 0.002), but not
      vascular endothelium and stroma, in women with recurrent miscarriage. Similarly,
      in women with unexplained infertility, eNOS was significantly higher (P < 0.03)
      in luminal epithelium but not in any other compartments compared with the control
      group. The levels of mRNA confirmed the protein data, demonstrating higher eNOS
      mRNA in the endometrium of women with recurrent miscarriage and unexplained
      infertility compared with controls. In conclusion, increased expression of eNOS
      in glandular and luminal epithelium of the endometrium in women with recurrent
      miscarriages and unexplained infertility suggests a detrimental effect of excess
      nitric oxide in endometrial receptivity and implantation.

PMID- 22877943
TI  - Evidence that miR-133a causes recurrent spontaneous abortion by reducing HLA-G
      expression.
AB  - Human leukocyte antigen (HLA)-G is thought to confer fetal-maternal tolerance and
      play a crucial role in ensuring a successful pregnancy. There is increasing
      evidence that HLA-G is regulated at the post-transcriptional level. This study
      investigated the role of miR-133a in regulating HLA-G expression and the
      pathogenesis of recurrent spontaneous abortion (RSA). Twelve patients (25-30
      years) with RSA at 7 gestational weeks were screened by array-based comparative
      genome hybridization: 16.7% were found to have an abnormal karyotype and all
      induced abortion (IA) patients had normal karyotype. The villi of RSA and IA
      patients with normal karyotype were further screened by miRNA microarrays. Multi
      software prediction and real-time PCR confirmed that miR-133a was most likely to
      bind to HLA-G 3' untranscribed region (UTR). Relevance analysis showed that,
      compared with IA villi, miR-133a was greatly overexpressed in RSA villi with
      normal karyotype (P<0.01), but not in abnormal RSA villi. A luciferase reporter
      assay suggested that miR-133a interacted with HLA-G 3' UTR. Overexpression of miR
      133a in JEG-3 cells decreased HLA-G expression at the protein level, with no
      effect on mRNA. These findings provide strong evidence that miR-133a regulates
      HLA-G expression by reducing translation and is involved in the pathogenesis of
      RSA.

PMID- 22877942
TI  - Dynamic profiles of Oct-4, Cdx-2 and acetylated H4K5 in in-vivo-derived rabbit
      embryos.
AB  - This study documents the spatial and temporal distribution of Oct-4, Cdx-2 and
      acetylated H4K5 (H4K5ac) by immunocytochemistry staining using in-vivo-derived
      rabbit embryos at different stages: day-3 compact morulae, day-4 early
      blastocysts, day-4 expanded blastocysts, day-5 blastocysts, day-6 blastocysts and
      day-7 blastocysts. The Oct-4 signal was stronger in the inner cell mass
      (ICM)/epiblast cells than in the trophectoderm (TE) cells in all blastocyst
      stages except day-4 expanded blastocysts, where the signal was similarly weak in
      both the ICM and TE cells. The Cdx-2 signal was first detected in a small number
      of TE cells of day-4 early blastocysts, and became evident in the TE cells
      exclusively afterwards. A consistently strong H4K5ac signal was observed in the
      TE cells in all blastocyst stages examined. In particular, this signal was
      stronger in the TE than in the ICM cells in day-4 early blastocysts, day-4
      expanded blastocysts and day-5 blastocysts. Double staining of H4K5ac with either
      Oct-4 or Cdx-2 on embryos at different blastocyst stages confirmed these
      findings. This work suggests that day 4 is a critical timing for lineage
      formation in rabbit embryos. A combination of Oct-4, Cdx-2 and H4K5ac can be used
      as biomarkers to identify different lineage cells in rabbit blastocysts.

PMID- 22877944
TI  - Timing of cell division in human cleavage-stage embryos is linked with blastocyst
      formation and quality.
AB  - Noninvasive markers of embryo quality are being sought to improve IVF success.
      The present study aimed to discover possible associations between embryo division
      kinetics in the cleavage stage, the subsequent ability of human embryos to reach
      the blastocyst stage and the resulting blastocyst morphology. A retrospective
      cohort study analysed 834 embryos from 165 oocyte donation couples using a time
      lapse monitoring system that allowed the recording of the exact timings for key
      events related to embryo development. Timing parameters were categorized into
      four quartiles. The probability of an embryo developing to a blastocyst was
      linked to a strict chronology of development. To further evaluate the
      relationships between these morphokinetic parameters and subsequent blastocyst
      formation, the ensuing blastocyst morphology was compared with a viability score
      based on a hierarchical classification of the cleavage-stage morphokinetic
      parameters. It is concluded that the kinetics of early embryo development and the
      potential for human embryos to develop to the blastocyst stage on day 5 are
      closely related and that time-lapse-based evaluation of the exact timing of early
      events in embryo development is a promising tool for the prediction of blastocyst
      formation and quality according to the proposed model.

PMID- 22877945
TI  - Pan-epicardial lineage tracing reveals that epicardium derived cells give rise to
      myofibroblasts and perivascular cells during zebrafish heart regeneration.
AB  - Myocardial infarction (MI) leads to a severe loss of cardiomyocytes, which in
      mammals are replaced by scar tissue. Epicardial derived cells (EPDCs) have been
      reported to differentiate into cardiomyocytes during development, and proposed to
      have cardiomyogenic potential in the adult heart. However, mouse MI models reveal
      little if any contribution of EPDCs to myocardium. In contrast to adult mammals,
      teleosts possess a high myocardial regenerative capacity. To test if this
      advantage relates to the properties of their epicardium, we studied the fate of
      EPDCs in cryoinjured zebrafish hearts. To avoid the limitations of genetic
      labelling, which might trace only a subpopulation of EPDCs, we used cell
      transplantation to track all EPDCs during regeneration. EPDCs migrated to the
      injured myocardium, where they differentiated into myofibroblasts and
      perivascular fibroblasts. However, we did not detect any differentiation of EPDCs
      nor any other non-cardiomyocyte population into cardiomyocytes, even in a context
      of impaired cardiomyocyte proliferation. Our results support a model in which the
      epicardium promotes myocardial regeneration by forming a cellular scaffold, and
      suggests that it might induce cardiomyocyte proliferation and contribute to
      neoangiogenesis in a paracrine manner.

PMID- 22877947
TI  - An evidence-based review of the incidence of CNS bleeding with anti-VEGF therapy
      in non-small cell lung cancer patients with brain metastases.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a key mediator of
      angiogenesis. Solid tumors, including non-small cell lung cancer (NSCLC), are
      dependent on angiogenesis for growth and metastasis. Anti-VEGF therapy has
      demonstrated clinical benefits in the first-line treatment of NSCLC. Central
      nervous system (CNS) metastases are a common occurrence among patients with lung
      cancer and confer significant morbidity and mortality. The risk of CNS hemorrhage
      in NSCLC patients receiving anti-VEGF therapy is still relatively unexplored
      because patients with CNS metastases have generally been excluded from trials of
      anti-VEGF therapy due to a perceived increased risk of cerebral hemorrhage.
      Recently, large prospective, randomized trials, open-label studies and
      observational cohort studies in NSCLC have provided data on the incidence of CNS
      hemorrhage in large patient populations, reflective of community practice.
      METHODS: We conducted a literature review for the available data on the incidence
      of CNS hemorrhage in NSCLC patients with brain metastases receiving anti-VEGF
      therapy. RESULTS: There is no significantly increased risk of CNS hemorrhage in
      patients with NSCLC and emerging (previously untreated) or pretreated CNS
      metastases receiving anti-VEGF therapy. CONCLUSIONS: We conclude that clinical
      trial data indicate that anti-VEGF therapy can be considered for NSCLC patients
      with emerging or pretreated CNS metastases.

PMID- 22877946
TI  - A cis-regulatory module upstream of deltaC regulated by Ntla and Tbx16 drives
      expression in the tailbud, presomitic mesoderm and somites.
AB  - Somites form by an iterative process from unsegmented, presomitic mesoderm (PSM).
      Notch pathway components, such as deltaC (dlc) have been shown to play a role in
      this process, while the T-box transcription factors Ntla and Tbx16 regulate
      somite formation upstream of this by controlling supply and movement of cells
      into the PSM during gastrulation and tailbud outgrowth. In this work, we report
      that Ntla and Tbx16 play a more explicit role in segmentation by directly
      regulating dlc expression. In addition we describe a cis-regulatory module (CRM)
      upstream of dlc that drives expression of a reporter in the tailbud, PSM and
      somites during somitogenesis. This CRM is bound by both Ntla and Tbx16 at a
      cluster of T-box binding sites, which are required in combination for activation
      of the CRM.

PMID- 22877948
TI  - MR imaging of the temporomandibular joint.
AB  - MR imaging allows detailed evaluation of temporomandibular (TMJ) anatomy because
      of its inherent tissue contrast and high resolution. Joint biomechanics can be
      assessed through imaging patients in the closed and open jaw positions. Despite
      the accuracy of MR imaging in detecting disc position, results must be
      interpreted together with clinical findings, because an anteriorly displaced disc
      can be seen in up to one-third of asymptomatic patients, and a normal disc
      position can be seen in up to one-quarter of symptomatic patients. Interpretation
      of MR imaging requires knowledge of the normal anatomy and an understanding of
      normal and abnormal biomechanics.

PMID- 22877949
TI  - Evaluation of orbital disorders and cranial nerve innervation of the extraocular
      muscles.
AB  - A wide range of orbital disorders, including an orbital mass, infection,
      inflammation, systemic disease, or intracranial lesions, may be encountered with
      imaging. Evaluation of orbital disorders requires the combination of accurate and
      relevant clinical information with an understanding of anatomy and pathologic
      processes. An imaging approach to an orbital differential diagnosis includes
      assessment for alteration of a normal orbital structure, a lesion that does not
      belong in the orbit, or alteration of the orbit from bone or periorbital
      disorders. This approach, combined with key elements of clinical history, leads
      to a narrower differential diagnosis and improved patient care.

PMID- 22877950
TI  - Patterns of perineural tumor spread in head and neck cancer.
AB  - Perineural tumor spread (PNS) is a mode of neoplastic spread whereby tumor cells
      use neural conduits to escape the borders of a primary tumor. MRI is generally
      favored over CT for evaluating PNS, and findings include obliteration of fat
      within skull base foramina, enlargement and enhancement of the involved nerves,
      and enlargement and destruction of the bony foramina. Careful examination of the
      entire course of the nerve allows detection of skip lesions. Recognition of the
      complete extent of PNS is crucial for correct treatment because it facilitates
      both surgical and radiotherapy targeting of entire extent of disease.

PMID- 22877951
TI  - Aggressive inflammatory and neoplastic processes of the paranasal sinuses.
AB  - Although uncommon, sinonasal malignancies and aggressive inflammatory processes
      are entities every radiologist will encounter during the evaluation of routine
      sinus imaging studies. A high index of suspicion is necessary for prompt
      diagnosis. It is important to consider aggressive inflammatory disease in all
      patients having routine sinus computed tomography because any delay in diagnosis
      can adversely affect the patients' care. Magnetic resonance (MR) will often
      provide a better assessment of the lesion extent, allowing for better surgical
      treatment. MR is crucial for the accurate assessment of neoplastic lesions. A
      proficient understanding of the complex anatomy of the region is essential.

PMID- 22877952
TI  - MR assessment of oral cavity carcinomas.
AB  - Approximately half of head and neck carcinomas arise from the oral cavity.
      Imaging plays an essential role in the preoperative evaluation of oral cavity
      carcinomas. MR imaging is particularly advantageous in the evaluation of the oral
      cavity, with better depiction of the anatomy in this region and reduction of
      dental artifacts compared with CT. MR is also the preferred imaging modality for
      the evaluation of bone marrow invasion and perineural tumor spread, which are
      findings critical for treatment planning. Advanced MR imaging techniques may
      potentially better delineate true tumor extent, determine lymph node metastases,
      and predict treatment response.

PMID- 22877953
TI  - Myocutaneous flaps and other vascularized grafts in head and neck reconstruction
      for cancer treatment.
AB  - This article addresses the clinical evaluation and some of the more common flaps
      and grafts used to reconstruct the surgical bed after excision of primary head
      and neck cancers and nodal metastases. This focused summary is intended to
      enhance the reader's understanding and improve the interpretation of
      posttreatment MR imaging. A practical approach to MR imaging evaluation of the
      postoperative reconstructed neck is presented. Readers of this article will
      become familiar with the normal appearances of commonly used flaps, recognize
      common complications, be able to delineate residual and recurrent neoplasm, and
      learn to avoid interpretative pitfalls.

PMID- 22877954
TI  - Evaluation of the sellar and parasellar regions.
AB  - The article reviews the anatomy and imaging evaluation of the sellar and
      parasellar regions. Both common and uncommon sellar and suprasellar masses are
      reviewed, focusing on a systematic approach to analysis and when appropriate,
      differential creation.

PMID- 22877955
TI  - Applications of magnetic resonance imaging in adult temporal bone disorders.
AB  - Magnetic resonance (MR) imaging has new applications in the assessment of
      temporal bone disorders. This article summarizes current MR imaging applications
      in evaluating adult temporal bone lesions according to their location, beginning
      from the most common indication, vestibular schwannoma. Inner ear lesions,
      petrous lesions, and middle ear lesions are discussed, including the role of
      diffusion-weighted imaging in cholesteatomas, external ear lesions, and a few
      systemic conditions. Although this article emphasizes the role of MR imaging, the
      diagnostic value of computed tomography scan associated with MR imaging is also
      stressed. The main indications of temporal bone MR imaging are summarized.

PMID- 22877956
TI  - Magnetic resonance imaging of the pediatric neck: an overview.
AB  - Evaluation of neck lesions in the pediatric population can be a diagnostic
      challenge, for which magnetic resonance (MR) imaging is extremely valuable. This
      article provides an overview of the value and utility of MR imaging in the
      evaluation of pediatric neck lesions, addressing what the referring clinician
      requires from the radiologist. Concise descriptions and illustrations of MR
      imaging findings of commonly encountered pathologic entities in the pediatric
      neck, including abnormalities of the branchial apparatus, thyroglossal duct
      anomalies, and neoplastic processes, are given. An approach to establishing a
      differential diagnosis is provided, and critical points of information are
      summarized.

PMID- 22877957
TI  - Fetal MRI: head and neck.
AB  - Abnormalities of the fetal head and neck may be seen in isolation or in
      association with central nervous system abnormalities, chromosomal abnormalities,
      and syndromes. Magnetic resonance imaging (MRI) plays an important role in
      detecting associated abnormalities of the brain as well as in evaluating for
      airway obstruction that may impact prenatal management and delivery planning.
      This article provides an overview of the common indications for MRI of the fetal
      head and neck, including abnormalities of the fetal skull and face, masses of the
      face and neck, and fetal goiter.

PMID- 22877958
TI  - Practical MR imaging in the head and neck. Preface.

PMID- 22877959
TI  - A mix of bulk and ready-to-use modified-texture food: impact on older adults
      requiring dysphagic food.
AB  - Ready-to-use modified-texture food (rMTF) products are commercially available and
      may have greater appeal than conventional in-house or commercial bulk modified
      texture food (cMTF) products. A nine-month pilot study using a prospective
      interrupted time-series design where participants (n = 42) served as their own
      controls investigated the impact of cMTF + rMTF on weight goals, weight, food
      intake, and co-morbidity. Seventy-four per cent of participants achieved their
      weight goals at the end of six months on rMTF and, although insignificant,
      participants did have a trend towards weight gain while on rMTF (OR 3.5 p = .16).
      Main-plate food intake (grams) was not significantly different over time, but a
      downwards trajectory suggests decreased consumption that was compensated for by a
      significantly higher fat intake during the intervention period (p = .01).
      Increased co-morbidity and a decreasing volume of food consumed are common in
      older adults with dysphagia, and enhanced food products are needed to meet
      nutrient needs. Methodological issues encountered in this study can provide
      guidance for future work.

PMID- 22877960
TI  - Placenta share discordance and umbilical artery Doppler change after antenatal
      betamethasone administration in monochorionic twins with selective intrauterine
      growth restriction: is there a link?
AB  - This study was designed to evaluate the degree of placenta share discordance in
      relation to the betamethasone-induced return of positive end-diastolic flow in
      monochorionic twin pregnancies with selective intrauterine growth restriction
      (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was
      defined as one twin having an estimated fetal weight below the 10th percentile
      combined with an estimated fetal weight discordance >25%. The umbilical artery
      Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the
      first dose of betamethasone administration was recorded. The estimated individual
      placental weight in monochorionic twins was obtained by cutting the placenta
      along the vascular equator into two territories; the placenta share discordance
      was calculated as [(estimated individual placental weight of appropriated for
      gestational age twin- estimated individual placental weight of growth restricted
      twin)/estimated individual placental weight of appropriated for gestational age
      twin] * 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced
      return of positive umbilical artery end-diastolic flow. The difference of
      placenta share discordance and birth weight discordance were not significantly
      different between twins with and without betamethasone-induced return of positive
      umbilical artery end-diastolic flow. Thus, according to our study results, it was
      proposed that although the placenta share discordance correlated with the
      abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the
      betamethasone-induced return of positive umbilical artery end-diastolic flow,
      however, did not reveal the similar relationship with the severity of placenta
      share discordance.

PMID- 22877962
TI  - Asenapine for elderly bipolar manic patients.
AB  - BACKGROUND: Bipolar disorder (BPD) in the elderly is probably heterogeneous and
      its etiopathogenesis is complex. The data for the treatment of late-life BPD are
      limited. Asenapine is approved in the United States for acute treatment of manic
      or mixed episodes of bipolar I disorder with or without psychotic features. AIM:
      We report the results of acute treatment with asenapine in elderly patients with
      BPD. METHOD: Elderly patients (N=11), mean age: 67.7 +/- 6.1 years, consecutively
      admitted to the psychogeriatric ward due to acute bipolar mania were treated by
      asenapine 10mg/BID monotherapy for 4 weeks. Safety and tolerability assessments
      included adverse events (AEs), laboratory values, and anthropometric measures.
      Response, a secondary assessment, was measured as change in Young Mania Rating
      Scale (YMRS) total score from baseline to week 4. RESULTS: One patient developed
      a rash on day 6 of treatment and one patient developed peripheral edema on day 14
      of treatment. Both AEs resolved rapidly following discontinuation of asenapine.
      Only mild sedation was reported by three patients. In all cases, mean (+/- SD)
      change (improvement) in YMRS total score at week 4 was -21.4 +/- 12.9 and 7/11
      (63.6%) of patients remitted (YMRS<=12). CONCLUSION: In this small open-label
      study of elderly patients with bipolar mania, acute treatment with asenapine was
      well tolerated and effective.

PMID- 22877961
TI  - Cognitive therapy for anxious depression in STAR(*) D: what have we learned?
AB  - BACKGROUND: Anxious depression, defined as MDD with high levels of anxiety
      symptoms, has been associated with lower rates of antidepressant response and
      remission as well as greater chronicity, suicidality and antidepressant side
      effect burden. The primary aim of this study was to assess the effectiveness of
      cognitive therapy (CT) alone or in combination with medications for anxious
      versus non-anxious depression. METHODS: We assessed the STAR(*)D study
      participants who were partial or non-responders to citalopram. Subjects were then
      either switched (n=696) to a new antidepressant or to CT alone, or they were kept
      on citalopram and augmented (n=577) with another antidepressant or CT. We
      compared response and remission rates, across treatment conditions, between those
      who met criteria for anxious depression and those who did not. RESULTS: Those
      with anxious depression had significantly lower remission rates based on the
      QIDS, whether assigned to switch or augmentation, compared to those with non
      anxious depression. Those with anxious depression, compared to those without, had
      significantly lower response rates based on the QIDS only in the switch group.
      There was no significant interaction between anxious depression and treatment
      assignment. LIMITATIONS: Limitations include the use of citalopram as the only
      Level 1 pharmacotherapy and medication augmentation option, the relatively small
      size of the CT arms, use of depression-focused CT rather than anxiety-focused CT,
      and focus on acute treatment outcomes. CONCLUSIONS: Individuals with anxious
      depression appear to experience higher risk of poorer outcome following
      pharmacotherapy and/or CT after an initial course of citalopram and continued
      efforts to target this challenging form of depression are needed.

PMID- 22877963
TI  - Distinguishing young people with emerging bipolar disorders from those with
      unipolar depression.
AB  - BACKGROUND: To facilitate early intervention, there is a need to distinguish
      unipolar versus bipolar illness trajectories in adolescents and young adults with
      adult-type mood disorders. METHODS: Detailed clinical and neuropsychological
      evaluation of 308 young persons (aged 12 to 30 years) with moderately severe
      unipolar and bipolar affective disorders. RESULTS: Almost 30% (90/308) of young
      people (mean age=19.4+/-4.4yr) presenting for care with affective disorders met
      criteria for a bipolar-type syndrome (26% with bipolar I). Subjects with bipolar-
      and unipolar-type syndromes were of similar age (19.8 vs. 19.2yr) and reported
      comparable ages of onset (14.5 vs. 14.3yr). Clinically, those subjects with
      unipolar and bipolar-type disorders reported similar levels of psychological
      distress, depressive symptoms, current role impairment, neuropsychological
      dysfunction and alcohol or other substance misuse. Subjects with unipolar
      disorders reported more social anxiety (p<0.01). Subjects with bipolar disorders
      were more likely to report a family history of bipolar (21% vs. 11%; [chi(2)=4.0,
      p<.05]) or psychotic (19% vs. 9%; [chi(2)=5.5, p<.05]), or substance misuse (35%
      vs. 23%; [chi(2)=3.9, p<.05]), but not depressive (48% vs. 53%; chi(2)=0.3,
      p=.582]) disorders. CONCLUSIONS: Young subjects with bipolar disorders were best
      discriminated by a family history of bipolar, psychotic or substance use
      disorders. Early in the course of illness, clinical features of depression, or
      neuropsychological function, do not readily differentiate the two illness
      trajectories.

PMID- 22877964
TI  - Sensitivity to depression or anxiety and subclinical cardiovascular disease.
AB  - BACKGROUND: Depressive and anxiety disorders are highly overlapping,
      heterogeneous conditions that both have been associated with an increased risk of
      cardiovascular disease (CVD). Cognitive vulnerability traits for these disorders
      could help to specify what exactly drives CVD risk in depressed and anxious
      subjects. Our aim is to examine sensitivity to depression or anxiety in
      association with indicators of subclinical CVD. METHODS: Data from 635
      participants (aged 20-66 years) of the Netherlands Study of Depression and
      Anxiety were analyzed. Depression sensitivity was measured by the revised Leiden
      Index of Depression Sensitivity. Anxiety sensitivity was measured by the Anxiety
      Sensitivity Index. Subclinical CVD was measured as (1) carotid intima-media
      thickness and plaque presence using B-mode ultrasonography and (2) central
      arterial stiffness (augmentation index) using calibrated radial applanation
      tonometry. RESULTS: After adjustment for sociodemographics, blood pressure, and
      LDL cholesterol, higher scores of anxiety sensitivity were associated with both
      increased likelihood of carotid plaques (OR per SD increase=1.34, 95%CI=1.06
      1.68) and increased arterial stiffness (beta=.06, p=.01). No significant
      associations were found with carotid intima-media thickness nor for depression
      sensitivity. LIMITATIONS: The cross-sectional design precludes causal inference.
      Current mood state could have influenced the self-reported sensitivity data.
      CONCLUSIONS: The presence of carotid plaques and central arterial stiffness was
      especially increased in subjects who tend to be highly fearful of anxiety-related
      symptoms. These observations suggest that vulnerability to anxiety, rather than
      to depression, represents a correlate of subclinical CVD.

PMID- 22877965
TI  - Predictors of employment in bipolar disorder: a systematic review.
AB  - BACKGROUND: Severe work impairment can be present for a considerable proportion
      of the course of bipolar disorder (BD) and is costly for governments, services
      and individuals. Understanding predictors of employment in BD is therefore
      crucial as some may be susceptible to interventions. We conducted a systematic
      review of prospective studies in order to identify predictors of employment in
      people with BD. METHODS: We searched Medline, PsychInfo, EMBASE and Web of
      Science databases, hand searched 3 journals and used predetermined criteria to
      select papers for full text inclusion. Sixty seven papers were identified. Nine
      met inclusion criteria, with a total sample of 3184. RESULTS: Studies included in
      this review identified cognitive deficits (67%, n=4), depression (43%, n=3) and
      level of education (33%, n=2) as predictors of employment in BD patients. Bipolar
      depression not only affects whether someone is employed but also time off work.
      Even sub-syndromal depression appears to damage employment prospects. Verbal
      memory and executive functioning appear to be predictors of work functioning.
      LIMITATIONS: Conclusions are based on a relatively small number of studies and
      are therefore subject to change with the addition of further studies. A formal
      meta-regression was not possible due to differences between measures of
      employment and work functioning. CONCLUSIONS: Better assessment and management of
      depression and cognitive difficulties could improve the occupational functioning
      of BD patients. There is a need for high quality longitudinal studies
      specifically designed to investigate predictors of employment in large bipolar
      disorder samples.

PMID- 22877966
TI  - Delayed sleep phase in young people with unipolar or bipolar affective disorders.
AB  - BACKGROUND: Circadian disturbances may play a key role in the pathogenesis of
      some forms of mood disorders. Despite marked changes in circadian rhythms during
      the normal course of adolescence and young adulthood, less is known about changes
      in the 24-h sleep-wake cycle in young persons with mood disorders. METHODS:
      Seventy-five young participants with mood disorders (unipolar: n=46, 20.1 +/- 4.7
      years old; bipolar I or II: n=29, 23.2 +/- 4.3) and 20 healthy participants (24.8
      +/- 2.5 years old) underwent actigraphy monitoring during a depressive phase over
      seven consecutive days and nights. Sleep phase delay was defined as mean sleep
      onset >= 1:30 am and/or sleep offset >= 1 0:00 am. RESULTS: A delayed sleep phase
      was found in 62% of participants with bipolar disorders when depressed, compared
      with 30% of those with unipolar depression (chi(2)=6.0, p=0.014) and 10% of
      control participants (chi(2)=11.2, p<0.001). Sleep offset times were
      significantly later in subjects with mood disorders compared to the control
      group, and later in those with bipolar as compared with unipolar disorders (all p
      <= 0.043). LIMITATIONS: This study was cross-sectional and the depressed groups
      were somewhat younger compared to the healthy controls. Longitudinal studies are
      required to determine the predictive significance of these findings. CONCLUSIONS:
      Young patients with mood disorders, especially those with bipolar disorders, are
      particularly likely to have a delayed sleep phase. Therapies focused on advancing
      sleep phase may be of specific benefit to these young persons.

PMID- 22877967
TI  - Local social support mitigates depression among women contending with spousal
      violence and husband's risky drinking in Mumbai slum communities.
AB  - BACKGROUND: Women living in slum communities in India too often contend with
      depression. Local social support in other national contexts has been shown to
      reduce such risks. Less research in this area has been done in India and
      specifically with monogamous wives. METHODS: This study involved a household
      sample of women reporting husband's partner violence or heavy alcohol use
      (N=220). Participants were assessed on high social support in the community, and
      number of depressed days in the past 30 day (dichotomized as 10+ vs.<10 day).
      Logistic regression analyses assessed associations between local social support
      and depression, adjusting for demographics, spousal violence, and husband risky
      alcohol use. RESULTS: High local social support was reported by 40% of women; 33%
      reported never having local social support. Women with high local social support
      were significantly less likely to report depression (AOR: 0.53, 95% CI: 0.30
      0.94), even after adjusting for husbands' recent spousal violence perpetration
      and his risky alcohol use, both of which were also significantly associated with
      depression. LIMITATIONS: The data analyzed for this study are vulnerable to self
      report and recall biases, as well as issues around social desirability. These
      analyses are further limited due to the use of single item measures to assess
      depression and local social support. CONCLUSIONS: Local social support reduces
      risk for depression among women in Mumbai contending with husbands' spousal
      violence and risky alcohol use. These findings support the likely utility of
      community-based social support building to reduce risk for depression among this
      vulnerable population of women.

PMID- 22877968
TI  - Burden of maternal bipolar disorder on at-risk offspring: a controlled study on
      family planning and maternal care.
AB  - INTRODUCTION: Bipolar disorder (BD) is a highly incapacitating disease typically
      associated with high rates of familial dysfunction. Despite recent literature
      suggesting that maternal care is an important environmental factor in the
      development of behavioral disorders, it is unclear how much maternal care is
      dysfunctional in BD subjects. OBJECTIVE: The objective of this study was to
      characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared
      to healthy controls with (PD) and without (NPD) other psychiatric diagnoses.
      MATERIALS AND METHODS: Thirty-four BD mothers and 106 controls underwent an
      interview about family planning and maternal care, obstetrical complications, and
      mother-child interactions. K-SADS-PL questions about violence exposure were used
      to ascertain domestic violence and physical/sexual abuse. RESULTS: BD mothers
      were less likely to have stable unions (45.5%; p<0.01) or to live with the
      biological father of their children (33.3%; p<0.01), but had higher educational
      level and higher rates of social security use/retirement. They also had fewer
      children and used less contraceptive methods than controls. Children of BD women
      had higher rates of neonatal anoxia, and reported more physical abuse (16.1%;
      p=0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of
      offspring suffered physical and/or psychological abuse. LIMITATIONS: Post hoc
      analysis, and the use of questions as a surrogate of symptoms as opposed to
      validated instruments. CONCLUSION: This is one of few reports confirming that
      maternal care given by BD women is dysfunctional. BD psychopathology can lead to
      poor maternal care and both should be considered important environmental risk
      factors in BD, suggesting that BD psychoeducation should include maternal care
      orientation.

PMID- 22877969
TI  - The development and validation of the Peradeniya Depression Scale (PDS)--a
      culturally relevant tool for screening of depression in Sri Lanka.
AB  - BACKGROUND: Cultural factors may influence the manner in which a given population
      interprets and conceptualizes their experience of depression. The aim of this
      study is to validate the Peradeniya Depression Scale (PDS), a locally created,
      culturally relevant tool for detection of depression in Sri Lanka. METHOD: Fifty
      currently depressed patients (diagnosed via the Structured Clinical Interview for
      DSM Disorders) and 50 (non-depressed) controls were administered the PDS.
      RESULTS: At a score of 10/25 the PDS showed a sensitivity 88.5% and specificity
      of 85.0% with regards to the detection of depression. Culturally appropriate
      statements, which referred to international criteria of depression and somatic
      symptoms, showed significantly higher odds of being positive in depressed
      patients compared to controls. LIMITATIONS: The PDS was validated among an
      outpatient population presenting to a psychiatry clinic in a government hospital
      in Peradeniya, Sri Lanka. While this is fairly representative of patients
      presenting to government hospital clinics in this country, further multi-centre
      studies in different areas of the country maybe useful. CONCLUSION: The PDS is
      the first screening tool for depression developed and validated in Sri Lanka,
      written in Sinhalese, taking into account cultural expressions and idioms of the
      illness. It shows satisfactory sensitivity and specificity as a screening tool
      for depression. The findings also suggest that it maybe worthwhile for Asian
      countries to consider adopting scales which are based on internationally accepted
      diagnostic criteria for depression, but which incorporate expressions that are
      more appropriate to their own culture and language.

PMID- 22877970
TI  - Gastric pneumatosis and acute massive gastric dilatation without specific cause.

PMID- 22877971
TI  - Pericardial fat necrosis presenting as acute pleuritic chest pain.

PMID- 22877972
TI  - Phenols of virgin olive oil protects nuclear DNA against oxidative damage in HeLa
      cells.
AB  - Oxidative DNA damage is an inescapable consequence for cells constantly exposed
      to oxidative stress derived from normal metabolic processes and from
      environmental factors. Phenolic compounds, which have strong antioxidant
      activity, prevent DNA damage by protecting the cells against harmful effects of
      oxidative stress. In this study, the effect of virgin olive oil phenolic extract
      (OOPE) was investigated on H2O2-induced mitochondrial DNA (mtDNA) and nuclear DNA
      (nDNA) damage in HeLa cells. DNA damage was assessed in mitochondria and two
      nuclear regions by using quantitative PCR (QPCR) assay. The cells were pre
      treated with non-cytotoxic doses of OOPE for 4 h, and DNA damage was determined.
      OOPE alone does not change the steady-state level of DNA damage. The oxidative
      stress generated with 750 MUM H2O2 caused two times greater damages in mtDNA
      compared to nDNA, which included the nonexpressed beta-globin region (1.507+/
      0.110 lesions/10 kb) and the expressed APEX1 gene (1.623+/-0.243 lesions/10 kb)
      with respect to the control region. When cells were preincubated with OOPE for 4
      h, nDNA damage under stress condition was completely inhibited; however, mtDNA
      damage was not affected by this procedure. These results suggest that OOPE has a
      protective effect against nDNA damage in HeLa cells.

PMID- 22877973
TI  - Achievements and future trends in the analysis of emerging organic contaminants
      in environmental samples by mass spectrometry and bioanalytical techniques.
AB  - Several groups of organic compounds have emerged as particularly relevant as
      environmental pollutants. These compounds, including new brominated flame
      retardants, disinfection by-products, drugs of abuse and their metabolites,
      hormones and other endocrine disrupting compounds, nanomaterials, perfluoroalkyl
      substances, pharmaceuticals and siloxanes among others, constitute new risks for
      environmental and human health. In order to face up to these new risk challenges
      there is an increasing need to assess their occurrence and behaviour in the
      environment, as well as, that of their degradation products. Therefore, during
      recent years an important part of research has been focused on to the improvement
      of analytical schemes for complex matrices, in which the new tendencies in sample
      preparation (e.g. online clean up systems), the development of new materials and
      new mass spectrometry analysers have played an important role. This paper
      presents a general overview of new analytical trends and potentials in trace
      analysis of emerging pollutants in the environment, including chromatographic
      techniques coupled to mass spectrometry, and bio analytical approaches
      (biosensors).

PMID- 22877974
TI  - Vitamin D deficiency is a problem for adult out-patients? A university hospital
      sample in Istanbul, Turkey.
AB  - OBJECTIVE: To investigate the frequency of vitamin D deficiency in relation to
      demographics, clinical diagnosis, season of measurement and laboratory parameters
      in adult out-patients. DESIGN: Descriptive, retrospective study concerning
      evaluation of the initial 25-hydroxyvitamin D (25(OH)D) levels determined at
      admission in relation to demographics, clinical diagnosis, season of measurement
      and laboratory parameters. 25(OH)D levels ,20 ng/ml were classified as
      deficiency, 20-30 ng/ml as insufficiency and .30 ng/ml as sufficiency. SETTING:
      Out-patient clinics at a tertiary care centre. SUBJECTS: A total of 2488 adult
      patients (mean age: 53?3 (SD 15?2) years; 85?2% were females) admitted to out
      patient clinics at Baskent University Istanbul Hospital were included. RESULTS:
      Mean level of 25(OH)D in the overall population was 17?4 (SD 11?5) ng/ml while
      insufficiency and deficiency were evident in 24% and 66% of patients,
      respectively. Mean 25(OH)D levels in males .45 years old were higher than in
      their female counterparts (19?4 (SD 11?3) ng/ml v. 17?8 (SD 12?2) ng/ml; P,0?05).
      Mean 25(OH)D levels obtained in summer (18?6 (SD 11?1) ng/ml) and autumn (23?3
      (SD 13?6) ng/ml) were significantly higher than levels in spring (16?1 (SD 10?3)
      ng/ml) and winter (14?6 (SD 10?2) ng/ml; P,0?01). Mean 25(OH)D levels were
      determined to be significantly lower in obese patients compared with non-obese
      patients (15?6 (SD 10?4) ng/ml v. 17?6 (SD 11?6) ng/ml; P,0?05). Levels of
      25(OH)D were significantly negatively correlated with serum parathyroid hormone
      levels (r520?194; P,0?001) while significantly positively correlated with
      phosphorus (r50?059; P,0?01) and HDL cholesterol (r50?070; P,0?01) levels.
      CONCLUSIONS: Our findings indicate that vitamin D deficiency is very common among
      out-patients in Turkey, regardless of gender and age, especially among obese
      people and during winter and spring.

PMID- 22877976
TI  - Hypothyroxinemia during pregnancy: the effect on neurodevelopment in the child.
AB  - CONTEXT: Experimental studies have shown that maternal hypothyroxinemia during
      early pregnancy is associated with poor neurodevelopment in affected offspring.
      OBJECTIVE: The aim of this study was to assess the impact of maternal serum free
      T4 on psychomotor development of offspring. MATERIALS AND METHODS: The study
      involved 147 women in the third trimester (week 37) of pregnancy. TSH and free T4
      serum levels were measured at 37 week gestation. The children were evaluated
      between 38 and 60 months of age by the McCarthy Scales of Children's Abilities.
      RESULTS: 54.4% of the women had a free T4 below the threshold of
      hypothyroxinemia. We find a significant effect of maternal hypothyroxinemia on
      the general cognitive index, and on perceptual-manipulative and memory
      coefficients.

PMID- 22877977
TI  - Helminths and skewed cytokine profiles increase tuberculin skin test positivity
      in Warao Amerindians.
AB  - The immune regulatory mechanisms involved in the acquisition of Mycobacterium
      tuberculosis infection in children are largely unknown. We investigated the
      influence of parasitic infections, malnutrition and plasma cytokine profiles on
      tuberculin skin test (TST) positivity in Warao Amerindians in Venezuela.
      Pediatric household contacts of sputum smear-positive tuberculosis (TB) cases
      were enrolled for TST, chest radiograph, plasma cytokine analyses, QuantiFERON-TB
      Gold In-Tube (QFT-GIT) testing and stool examinations. Factors associated with
      TST positivity were studied using generalized estimation equations logistic
      regression models. Of the 141 asymptomatic contacts, 39% was TST-positive. After
      adjusting for age, gender and nutritional status, TST positivity was associated
      with Trichuris trichiura infections (OR 3.5, 95% CI 1.1-11.6) and low circulating
      levels of T helper 1 (Th1) cytokines (OR 0.51, 95% CI 0.33-0.79). Ascaris
      lumbricoides infections in interaction with Th2- and interleukin (IL)-10
      dominated cytokine profiles were positively associated with TST positivity (OR
      3.1, 95% CI 1.1-8.9 and OR 2.4, 95% CI 1.04-5.7, respectively). A negative
      correlation of QFT-GIT mitogen responses with Th1 and Th2 levels and a positive
      correlation with age were observed (all p < 0.01). We conclude that helminth
      infections and low Th1 cytokine plasma levels are significantly associated with
      TST positivity in indigenous Venezuelan pediatric TB contacts.

PMID- 22877978
TI  - Reversible pulmonary hypertension associated with lungworm infection in a young
      cat.
AB  - Two ten-week-old kittens presented with dyspnea. Two weeks later dyspnea had
      worsened and both kittens had developed a heart murmur. One kitten died and
      necropsy showed severe granulomatous pneumonia and moderate bronchi(oli)tis and
      peribronchi(oli)tis caused by Aelurostrongylus abstrusus. The results from
      echocardiography, thoracic radiography and the other kitten's fecal examination
      were interpreted as severe parasitic pneumonia caused by A. abstrusus infection
      with pulmonary hypertension. Repeated administration of milbemycine-oxime and
      praziquantel resulted in cessation of larvae shedding and resolution of clinical,
      radiographic and echocardiographic signs of bronchopneumonia and pulmonary
      hypertension.

PMID- 22877979
TI  - Comment on Iacovidou, E.; Ohandja, D.-G. and Voulvoulis, N. (2012) Food waste
      disposal units in UK households: the need for policy intervention. Science of the
      Total Environment 423 1-7.

PMID- 22877980
TI  - Dedication of the special issue to Colin Neal.

PMID- 22877982
TI  - Inferring local ecological processes amid species pool influences.
AB  - Resolving contingencies in community ecology requires comparative studies of
      local communities along broad-scale environmental gradients and in different
      biogeographic regions. However, comparisons of local ecological processes among
      regions require a synthetic understanding of how the species pool of potential
      community members influences the structure of ecological communities. Here, we
      outline an integrative approach for quantifying local ecological processes while
      explicitly accounting for species pool influences. Specifically, we highlight the
      utility of combining geographically replicated local studies, null models of
      community structure, and ecologically explicit definitions of the species pool as
      a means to compare predominant ecological processes among regions. By uniting
      concepts and tools from community ecology and macroecology, this approach might
      facilitate synthesis and resolve many perceived ecological contingencies.

PMID- 22877981
TI  - Stress effects caused by the expression of a mutant cellobiohydrolase I and
      proteasome inhibition in Trichoderma reesei Rut-C30.
AB  - Trichoderma reesei Rut-C30 is used widely as an expression host for various gene
      products. We have explored cellular effects caused by the expression of a mutant
      form of cellobiohydrolase I (CBHI), the major secreted protein of T. reesei using
      biochemical and transcriptomic analyses and confocal laser scanning microscopy.
      The mutated CBHI was tagged fluorescently with Venus to establish the subcellular
      location of the fusion protein and its potential association with the proteasome,
      an organelle assigned for the disposal of misfolded proteins. Expression of the
      mutant CBHI in the high protein-secreting host Rut-C30 caused physiological
      changes in the fungal hyphae, affected protein secretion and elicited ER stress.
      A massive upregulation of UPR- and ERAD-related genes sec61, der1, uba1, bip1,
      pdi1, prp1, cxl1 and lhs1 was observed by qRT-PCR in the CBHIDelta4-Venus strain
      with four mutations introduced in the DNA encoding the core domain of CBHI.
      Further stress was applied to this strain by inhibiting function of the
      proteasome with MG132 (N-benzoylcarbonyl(Cbz)-Leu-Leu-leucinal). The effect of
      MG132 was found to be specific to the proteasome-associated genes. There are no
      earlier reports on the effect of proteasome inhibition on protein quality control
      in filamentous fungi. Confocal fluorescence microscopy studies suggested that the
      mutant CBHI accumulated in the ER and colocalized with the fungal proteasome.
      These results provide an indication that there is a limit to how far T. reesei
      Rut-C30, already under secretion stress, can be pressed to produce higher protein
      yields.

PMID- 22877983
TI  - The future of fish.
AB  - Recently, the global state of marine fisheries and its effects on ecosystems have
      received much scientific (and public) scrutiny. There is little doubt that global
      limits to exploitation have been reached and that recovery of depleted stocks
      must become a cornerstone of fisheries management. Yet, current trends appear to
      be diverging between well-assessed regions showing stabilization of fish biomass
      and other regions continuing to decline. This divergence can be explained by
      improved controls on exploitation rates in several wealthy countries, but low
      management capacity elsewhere. Here, we identify an urgent need to direct
      priorities towards 'fisheries-conservation hotspots' of increasing exploitation
      rates, high biodiversity, and poor management capacity, and conclude that the
      future of fish depends, at least in part, on redoubling science, co-management
      and conservation efforts in those regions.

PMID- 22877984
TI  - Making use of the evidence to guide coverage decisions.

PMID- 22877985
TI  - Using evidence to inform coverage decisions: the Washington State experience.
AB  - To address the high cost, insufficient quality, and overutilization of specific
      medical technologies, the Washington State Health Technology Assessment Program
      was founded in 2007. This program produces binding decisions on which medical
      procedures and other technologies state-funded medical plans may cover. These
      evidence-based policy decisions are based on formal assessment of the medical
      evidence founded around the questions of technology effectiveness, safety, and
      cost. To date, the committee has evaluated a high proportion of radiologic
      technologies, with mixed decisions regarding coverage. Evidence-based policy can
      provide a valuable contribution to improving the quality of medical care through
      limiting public resources to those interventions of proven effectiveness.

PMID- 22877986
TI  - Liver lesions discovered incidentally on ultrasound: evaluation of reader ability
      to characterize lesions on MRI without intravenous contrast.
AB  - RATIONALE AND OBJECTIVES: Liver lesions incidentally discovered on ultrasound
      (US) are often further evaluated with magnetic resonance imaging (MRI). The
      purpose of this study is to evaluate the added effectiveness of contrast-enhanced
      MRI, compared to noncontrast MRI, to correctly guide management of liver lesions
      incidentally identified on ultrasound in patients with low pretest probability of
      malignancy. We conducted the evaluation using a multireader study. MATERIALS AND
      METHODS: Liver MRI studies ordered to evaluate incidental liver US lesions were
      selected for analysis. Patients with no prior history of cancer or chronic liver
      disease who had 2 years of clinical follow-up (72 patients) were selected to
      ensure low pretest probability of malignancy and adequate follow-up to establish
      proof of diagnosis. Fifty of these studies were randomly selected and analyzed by
      two abdominal radiologists. In the initial interpretation session, only
      nonenhanced images were reviewed; after 6 weeks, the complete exam including the
      contrast enhanced images were viewed. Differences in interpretation between the
      noncontrast and contrast enhanced reading sessions were assessed. RESULTS: Sixty
      nine patients (95.8%) had no abnormalities, benign masses, or hepatic steatosis
      accounting for the ultrasound findings. One patient was newly diagnosed with
      hereditary hemochromatosis, and 2 patients were newly diagnosed with metastatic
      disease. The most likely diagnosis changed for 15 of the lesions described by
      reader A, and 16 by reader B. The majority of these changes (26/31 lesions, 84%)
      were from one benign entity to another. Five of 31 (16%) of the changes involved
      that of a benign entity to a malignant one. Reader A recommended additional
      contrast enhanced imaging in 13/50 (26%) patients; reader B, 9/50 (18%) patients.
      After viewing the nonenhanced images, both readers recommended that all patients
      with eventual malignancies return for contrast administration and/or biopsy.
      After viewing the contrast-enhanced imaging, both readers accurately diagnosed
      all malignancies. Patient-based analysis receiver operating characteristic curves
      demonstrated no significant difference between the enhanced and noncontrast limbs
      of the study, and no significant difference between readers. CONCLUSION: Most of
      the changes in lesion detection and characterization made after contrast
      administration were clinically insignificant. In the lesions in which clinically
      important differences were made, both radiologists recommended additional imaging
      or biopsy that would have eventually led to the correct diagnosis. None of the
      patients with malignancy was categorized as completely benign either on
      noncontrast or contrast-enhanced imaging. This supports the utility of initially
      performing a noncontrast examination in a population with a low pretest
      probability of malignancy, especially those in whom gadolinium administration is
      contraindicated.

PMID- 22877988
TI  - A new alarm system.

PMID- 22877987
TI  - MRI-guided biopsy to correlate tissue specimens with MR elastography stiffness
      readings in liver transplants.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance elastography (MRE) can noninvasively
      measure the stiffness of liver tissue and display this information in anatomic
      maps. Magnetic resonance imaging (MRI) guidance has not previously been used to
      biopsy segments of heterogeneous stiffness identified on MRE. Dedicated study of
      MRE in post-liver transplant patients is also limited. In this study, the ability
      of real-time MRI to guide biopsies of segments of the liver with different MRE
      stiffness values in the same post-transplant patient was assessed. MATERIALS AND
      METHODS: MRE was performed in 9 consecutive posttransplant patients with history
      of hepatitis C. Segments of highest and lower stiffness on MRE served as targets
      for subsequent real-time MRI-guided biopsy using T2-weighted imaging. The ability
      of MRI-guided biopsy to successfully obtain tissue specimens was assessed. The
      Wilcoxon signed-rank test was used to compare mean stiffness differences for
      highest and lower MRE stiffness segments, with alpha = 0.05. RESULTS: MRI
      guidance allowed successful sampling of liver tissue for all (18/18) biopsies.
      There was a statistically significant difference in mean MRE stiffness values
      between highest (4.61 +/- 1.99 kPa) and lower stiffness (3.03 +/- 1.75 kPa) (P =
      .0039) segments biopsied in the 9 posttransplant patients. CONCLUSION: Real-time
      MRI can guide biopsy in patients after liver transplantation based on MRE
      stiffness values. This study supports the use of MRI guidance to sample tissue
      based on functional information.

PMID- 22877989
TI  - Over-expression of AQP7 contributes to improve insulin resistance in adipocytes.
AB  - OBJECTIVE: Aquaglyceroporin 7 (AQP7) is required for efflux of glycerol from
      adipocytes. In this study, we aimed to analyze expression profiles of AQP7 in the
      different differentiation phases of adipocytes and to investigate the role of
      AQP7 in the insulin resistance of adipocytes. METHODS: 3T3-L1 pre-adipocyte cells
      were induced to be fully differentiated adipocytes and then insulin resistance
      was induced by Dexamethasone (DXM) or TNF-alpha. Adenovirus vector with over
      expression AQP7 (Ad-AQP7) was constructed and transfected into adipocytes. The
      expression level of AQP7 and phosphorylated PKB (p-PKB) were measured. The
      glycerol released from adipocytes and glucose consuming rate were tested too.
      RESULTS: AQP7 expression was gradually up-regulated along with the
      differentiation processing of 3T3-L1 preadipocytes, which was consistent with the
      expression level of p-PKB. Dexamethasone down-regulated the expression of AQP7, p
      PKB and the glycerol content in adipocytes. Over-expression of AQP7 by
      transfecting Ad-AQP7 to insulin resistant adipocytes restored the phosphorylation
      of PKB and attenuated the glycerol secretion and glucose consuming rate of
      adipocytes. CONCLUSIONS: AQP7 is down-regulated in adipocytes with insulin
      resistance. The over-expression of AQP7 contributes to improve insulin resistance
      in adipocytes, which is potentially correlated with the increased phosphorylation
      of PKB.

PMID- 22877990
TI  - Rat and human fatty acid amide hydrolases: overt similarities and hidden
      differences.
AB  - Fatty acid amide hydrolase (FAAH) is a membrane protein that plays a relevant
      role in the metabolism of fatty acid amides and esters. It degrades important
      neurotransmitters such as oleamide and anandamide, and it has been involved in a
      number of human pathological conditions, representing therefore a valuable target
      for biochemical and pharmacological research. In this study, we have investigated
      in vitro the structure-function relationship of rat and human FAAHs. In
      particular circular dichroism, fluorescence spectroscopy and light scattering
      measurements have been performed, in order to characterize the structural
      features of the two proteins, both in the presence and absence of the
      irreversible inhibitor methoxyarachidonyl-fluorophosphonate. The results
      demonstrate that the structural dynamics of the two FAAHs are different, despite
      their high sequence homology and overall similarity in temperature-dependence.
      Additionally, membrane binding and kinetic assays of both FAAHs indicate that
      also the functional properties of the two enzymes are different in their
      interaction with lipid bilayers and with exogenous inhibitors. These findings
      suggest that pre-clinical studies of FAAH-dependent human diseases based only on
      animal models should be interpreted with caution, and that the efficacy of new
      drugs targeted to FAAH should be tested in vitro, on both rat and human enzymes.

PMID- 22877991
TI  - Physiological roles of phosphatidylethanolamine N-methyltransferase.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes the methylation of
      phosphatidylethanolamine to phosphatidylcholine (PC). This 22.3 kDa protein is
      localized to the endoplasmic reticulum and mitochondria associated membranes of
      liver. The supply of the substrates AdoMet and phosphatidylethanolamine, and the
      product AdoHcy, can regulate the activity of PEMT. Estrogen has been identified
      as a positive activator, and Sp1 as a negative regulator, of transcription of the
      PEMT gene. Targeted inactivation of the PEMT gene produced mice that had a mild
      phenotype when fed a chow diet. However, when Pemt(-/-) mice were fed a choline
      deficient diet steatohepatitis and liver failure developed after 3 days. The
      steatohepatitis was due to a decreased ratio of PC to phosphatidylethanolamine
      that caused leakage from the plasma membrane of hepatocytes. Pemt(-/-) mice
      exhibited attenuated secretion of very low-density lipoproteins and homocysteine.
      Pemt(-/-) mice bred with mice that lacked the low-density lipoprotein receptor,
      or apolipoprotein E were protected from high fat/high cholesterol-induced
      atherosclerosis. Surprisingly, Pemt(-/-) mice were protected from high fat diet
      induced obesity and insulin resistance compared to wildtype mice. If the diet
      were supplemented with additional choline, the protection against obesity/insulin
      resistance in Pemt(-/-) mice was eliminated. Humans with a Val-to-Met
      substitution in PEMT at residue 175 may have increased susceptibility to
      nonalcoholic liver disease. This article is part of a Special Issue entitled
      Phospholipids and Phospholipid Metabolism.

PMID- 22877992
TI  - New insights into the role of sphingosine 1-phosphate and lysophosphatidic acid
      in the regulation of skeletal muscle cell biology.
AB  - Lysophospholipids are bioactive molecules that are implicated in the control of
      fundamental biological processes such as proliferation, differentiation, survival
      and motility in different cell types. Here we review the role of sphingosine 1
      phosphate (S1P) and lysophosphatidic acid (LPA) in the regulation of skeletal
      muscle biology. Indeed, a wealth of experimental data indicate that these
      molecules are crucial players in the skeletal muscle regeneration process, acting
      by controllers of activation, proliferation and differentiation not only of
      muscle-resident satellite cells but also of mesenchymal progenitors that
      originate outside the skeletal muscle. Moreover, S1P and LPA are clearly involved
      in the regulation of skeletal muscle metabolism, muscle adaptation to different
      physiological needs and resistance to muscle fatigue. Notably, studies
      accomplished so far, have highlighted the complexity of S1P and LPA signaling in
      skeletal muscle cells that appears to be further complicated by their close
      dependence on functional cross-talks with growth factors, hormones and cytokines.
      Our increasing understanding of bioactive lipid signaling can individuate novel
      molecular targets aimed at enhancing skeletal muscle regeneration and reducing
      the fibrotic process that impairs full functional recovery of the tissue during
      aging, after a trauma or skeletal muscle diseases. This article is part of a
      Special Issue entitled Advances in Lysophospholipid Research.

PMID- 22877993
TI  - Standard triple and sequential therapies for Helicobacter pylori eradication: an
      update.
AB  - H. pylori infection remains a worldwide spread disease with a definite morbidity
      and mortality. Unfortunately, no current therapy regimen is able to cure the
      infection in all treated patients. The efficacy of the widely recommended triple
      therapies is decreasing, and a novel 10-day sequential therapy has been proposed.
      Data of 3 previous meta-analyses showed a significantly higher eradication rate
      following the sequential as compared to the 7-10 days triple therapies. The
      sequential therapy achieved significantly better results than triple therapies in
      children, elderly patients, non-ulcer dyspepsia patients, and in those infected
      with resistant strains towards either clarithromycin or metronidazole. We
      identified further 10 randomized trials. By pooling data, H. pylori infection was
      cured in 2,454 (86%; 95% CI: 84.7-87.3) out of 2,853 patients with the sequential
      therapy and in 2,320 (75.3%; 95% CI: 73.8-76.9) out of 3,079 patients treated
      with standard triple therapies (p<0.001), corresponding to a number to treat
      (NNT) of 9. The comparison between the 10-day sequential regimen and 14-day
      triple therapies deserves further investigations.

PMID- 22877994
TI  - Immune manipulation for Graves' disease: re-exploring an unfulfilled promise with
      modern translational research.
AB  - Although Graves' disease is the commonest autoimmune thyroid disorder, current
      therapeutics typically center on the eradication of the antigenic stimulus (i.e.
      thyroid gland) rather than radically tackling the underlying autoimmune
      processes. Consequently, it is not a surprising fact that Graves' disease remains
      essentially a chronic drug-dependent ailment afflicting untold numbers worldwide
      for decades despite progress in deciphering its autoimmune nature. Addressing the
      latter is key to a future cure as underscored by appropriate, albeit crude, proof
      of-concept scenarios of clinical remissions achieved with hematopoietic stem cell
      transplantation, immune down-regulation during pregnancy, use of corticosteroids
      or immunosuppressives, and cytokine biologics in animal models. Ongoing basic and
      translational research to further elucidate and refine our understanding of the
      pathogenesis of Graves' disease holds the promise of unraveling novel immune
      manipulative techniques that will bring the world a step closer to the elusive
      cure of the underlying autoimmunity amidst skepticisms on the value of the
      science from the present lack of paralleled advances at the bedside. We review
      the updated literature and describe the forms of immune manipulation hitherto
      explored that will offer a route to a future cure, from thionamides,
      hematopoietic stem cell transplantation to the latest immunomodulatory agents.

PMID- 22877995
TI  - Refractory status epilepticus: electroconvulsive therapy as a possible
      therapeutic strategy.
AB  - Refractory status epilepticus (SE) is a current daily therapeutic challenge.
      Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric
      disorders, is known to raise the seizure threshold. As such, ECT could be of
      major interest in refractory SE. In this paper, we provide a brief overview of
      ECT in refractory SE. Although no placebo-controlled or open-label study has been
      published on the efficacy or safety of ECT in refractory SE, eight case reports
      have been identified. SE cessation was obtained in 80% of cases, and complete
      recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT
      parameters used in these articles, we identified some common features that may be
      recommended for the use of ECT in refractory SE. ECT might be a viable
      therapeutic strategy for the most resistant and severe cases of SE, particularly
      after the failure of two inductions of anesthetic coma. This potential indication
      highlights the urgent need for clinical trials that assess the usefulness of ECT
      in refractory SE.

PMID- 22877996
TI  - The PRRT2 mutation c.649dupC is the so far most frequent cause of benign familial
      infantile convulsions.
AB  - PURPOSE: Mutations in the PRRT2 gene have been recently described as a cause of
      paroxysmal kinesigenic dyskinesia, infantile convulsions with choreoathetosis
      syndrome and, less often, infantile convulsions. We have analysed the frequency
      of PRRT2 mutations in families with benign familial infantile convulsions without
      paroxysmal kinesigenic dyskinesia. METHODS AND RESULTS: Direct sequencing of the
      coding region identified the PRRT2 mutation c.649dupC in 5/5 families with
      infantile convulsions. The mutation was present in 23 family members, of which 18
      were clinically affected and 2 were obligate carriers. The affected carriers of
      this mutation presented with different types of epileptic seizures during early
      childhood but did not develop additional neurological symptoms later in life.
      CONCLUSION: Our data demonstrate that the PRRT2 mutation c.649dupC is a frequent
      cause of benign familial infantile convulsions.

PMID- 22877997
TI  - Influences of early shift work on the diurnal cortisol rhythm, mood and sleep:
      within-subject variation in male airline pilots.
AB  - We aimed to investigate how early and late work shifts influenced the diurnal
      cortisol rhythm using a within-subjects study design. Participants were 30
      healthy male non-smoking pilots, mean age 39.4, employed by a short-haul airline.
      The standard rotating shift pattern consisted of 5 early shifts (starting before
      0600 h), followed by 3 rest days, 5 late shifts (starting after 1200 h) and 4
      rest days. Pilots sampled saliva and completed subjective mood ratings in a
      logbook 6 times over the day on two consecutive early shift days, two late days
      and two rest days. Sampling was scheduled at waking, waking+30 m, waking+2.5 h,
      waking+8 h, waking+12 h and bedtime. Waking time, sleep duration, sleep quality
      and working hours were also recorded. Cortisol responses were analysed with
      repeated measures analysis of variance with shift condition (early, late, rest)
      and sample time (1-6) as within-subject factors. Early shifts were associated
      with a higher cortisol increase in response to awakening (CAR(i)), a greater
      total cortisol output over the day (AUC(G)) and a slower rate of decline over the
      day than late shifts or rest days. Early shifts were also associated with shorter
      sleep duration but co-varying for sleep duration did not alter the effects of
      shift on the cortisol rhythm. Both types of work shift were associated with more
      stress, tiredness and lower happiness than rest days, but statistical adjustment
      for mood ratings did not alter the findings. Early shift days were associated
      with significantly higher levels of circulating cortisol during waking hours than
      late shifts or rest days.

PMID- 22877999
TI  - Twin-singleton differences in intelligence: a register-based birth cohort study
      of Norwegian males.
AB  - The aim was to determine the difference in intelligence between singletons and
      twins in young adulthood. Data from the Medical Birth Register of Norway were
      linked with register data from the Norwegian National Conscript Service. The
      study base consisted of data on the 445,463 males who were born alive in either
      single or twin births in Norway during 1967-1984 and who were examined at the
      time of the mandatory military conscription (age 18-20). Within this study base,
      there were data on 1,653 sibships of full brothers that included at least one man
      born in single birth and at least one man born in twin birth (4,307 persons,
      including 2,378 twins and 1,929 singletons). The intelligence scores of the
      singletons were 11% (95% confidence interval [CI]: 9-14%) of a standard deviation
      higher than those of the twins, after adjustment for birth year, birth order,
      parental ages at delivery, parental education levels, and other factors. The
      adjusted within-family difference was also 11% (95 % CI: 6-16%) of a standard
      deviation, indicating that unmeasured factors shared by siblings (e.g., maternal
      body height) have not influenced the estimate in important ways. When gestational
      age at birth was added to the model, the estimate for the difference in
      intelligence score was approximately the same. Including birth weight in the
      model strongly reduced the estimate. In conclusion, twins born in Norway during
      1967-1984 had slightly lower intelligence in early adulthood compared with the
      singletons.

PMID- 22878000
TI  - A polyelectrolyte-surfactant complex as support layer for membrane
      functionalization.
AB  - A polyelectrolyte-surfactant complex, polyallylamine-dodecylsulfate system, is
      presented as an alternative method for the modification of membranes. Due its
      chemical structure, the complex, once casted on a surface, is highly stable in
      aqueous solutions. This allows modifying with the same method different types of
      membranes, exemplified here by alumina and polycarbonate. Using different
      strategies, the complex system can also incorporate other elements useful for
      catalysis, biorecognition, or separation. Two applications are presented: the
      incorporation of gold nanoparticles to catalyze the reduction of 4-nitrophenol
      using a polycarbonate membrane, and the modification of alumina with a biotin
      derivative for the recognition of avidin in label-free sensors.

PMID- 22877998
TI  - Inhibition of 5alpha-reductase attenuates behavioral effects of D1-, but not D2
      like receptor agonists in C57BL/6 mice.
AB  - Converging lines of evidence point to the involvement of neurosteroids in the
      regulation of dopamine (DA) neurotransmission and signaling, yet the
      neurobiological bases of this link remain poorly understood. We previously showed
      that inhibition of steroid 5alpha-reductase (5alphaR), the key rate-limiting
      enzyme in neurosteroidogenesis, attenuates the behavioral effects of non
      selective DA receptor agonists in rats, including stereotyped responses and
      sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the
      acoustic startle reflex. Since previous findings suggested that the role of DA
      D(1)- and D(2)-like receptor families in behavioral regulation may exhibit broad
      interspecies and interstrain variations, we assessed the impact of 5alphaR
      blockade on the behavioral effects of DAergic agonists in C57BL/6 mice. The
      prototypical 5alphaR inhibitor finasteride (FIN; 25-50 mg/kg, intraperitoneally,
      IP) dose-dependently countered the PPI deficits and the enhancement of rearing
      responses induced by the full D(1)-like receptor agonist SKF-82958 (0.3 mg/kg,
      IP); however, FIN did not significantly affect the hyperlocomotive and startle
      attenuating effects of SKF-82958. Whereas the D(2)-like receptor agonist
      quinpirole (QUIN; 0.5 mg/kg, IP) did not induce significant changes in PPI, the
      combination of this agent and FIN surprisingly produced marked gating and startle
      deficits. In contrast with previous data on rats, FIN did not affect the
      reductions of startle reflex and PPI produced by the non-selective DAergic
      agonist apomorphine (APO; 0.5 mg/kg, IP). These findings collectively indicate
      that, in C57BL/6 mice, 5alphaR differentially modulates the effects of D(1)- and
      D(2)-like receptor agonists in behavioral regulation.

PMID- 22878001
TI  - Poly(tetrafluoroethylene) composite membranes coated with urchin-like polyaniline
      hiberarchy: preparation and properties.
AB  - Spiny polyaniline (PANI) spheres (urchin-like) were coated on a
      poly(tetrafluoroethylene) (PTFE) membrane via a counter-diffuse interfacial
      oxidation polymerization of aniline in an aqueous medium. The produced composite
      membrane has both unexpected superhydrophilicity and conductivity. The
      microstructure and morphology of the composite membrane were characterized by
      FTIR, UV-vis, XRD, TGA, and SEM. Effects of reagent concentrations and
      polymerization time on the membrane morphology and properties were studied
      systematically. A possible formation mechanism of the urchin-like polyaniline
      nanospheres on PTFE surface has been briefly discussed. The co-effect of both
      spherical micelles formed by Nafion and nanofibrous micelles formed by aniline/p
      toluenesulfonic acid was considered to be a reason to produce the urchin-like
      PANI nanospheres. The PTFE/Nafion/PANI composite membrane showed a convertible
      hydrophilic/hydrophobic feature via adjusting acidity/alkalinity of an aqueous
      medium and also was able to adsorb heavy metal-ions from the medium.

PMID- 22878002
TI  - Enhanced adsorption of puerarin onto a novel hydrophilic and polar modified post
      crosslinked resin from aqueous solution.
AB  - A novel of hydrophilic and polar N-vinylpyrrolidone modified post-crosslinked
      resin was synthesized and the adsorption behaviors toward puerarin from aqueous
      solution were investigated. The post-crosslinked adsorbent PNVP-DVBpc was
      prepared by Friedel-Crafts reaction of residual double bonds without external
      crosslinking agent. The specific surface area of precursor PNVP-DVB increased
      obviously after post-crosslinking modification. The synthesized adsorbents were
      characterized by BET surface area, Fourier transform infrared (FTIR), and
      scanning electron microscopy (SEM). The adsorption behaviors of puerarin from
      aqueous solution onto precursor PNVP-DVB and post-crosslinked adsorbent PNVP
      DVBpc were thoroughly researched. Commercial polymeric adsorbents Amberlite XAD-4
      and AB-8 were chosen as the comparison. Among the four media, PNVP-DVBpc
      presented the largest adsorption capacity of puerarin, which resulted from the
      synergistic effect of high specific surface area and polar groups (amide groups)
      onto the adsorbent matrix. Experimental results showed that equilibrium isotherms
      could be fitted by Freundlich model and the kinetic data could be characterized
      by pseudo-second order model reasonably. Column adsorption experiments indicated
      that the puerarin could be completely desorbed by 4.0 BV industrial alcohol.
      Continuous column adsorption-regeneration cycles demonstrated the PNVP-DVBpc
      without any significant adsorption capacity loss during operation.

PMID- 22878003
TI  - Reduction of perchlorate using zero-valent titanium (ZVT) anode: kinetic models.
AB  - The kinetics of perchlorate reduction by zero-valent titanium (ZVT) undergoing
      electrical pitting corrosion was described by interactions of two domains (pit
      and solution). Two kinetic models were developed based on two possible inhibition
      mechanisms. A competitive adsorption model was developed based on surface
      coverage of perchlorate and chloride on bare ZVT, and a Ti(II) consumption model
      was developed based on Ti(II) oxidation by electrochemically developed chlorine.
      Both models well predicted perchlorate concentration changes in the solution. The
      competitive adsorption model showed that chloride has a higher adsorption
      affinity on both sites where oxidative dissolution of ZVT occurs and where
      chloride oxidation occurs. Also, the rates of perchlorate removal and chloride
      oxidation were directly proportional to current applied. For the Ti(II)
      consumption model, the rate constant of Ti(II) production was dependent on
      current. The rate of chloride oxidation is also believed to be proportional to
      current, but this conclusion cannot be made with confidence. Both kinetic models
      described changes in perchlorate concentration well. However, the Ti(II)
      consumption model was limited in its ability to predict chloride concentration.
      This limitation was probably caused by a lack of available information like
      electrochemical oxidation of chloride on bare ZVT and Ti(II) oxidation by
      chlorine.

PMID- 22878004
TI  - Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding
      protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity
      and musculoskeletal toxicity in rats.
AB  - Cardiotoxicity and musculoskeletal toxicity can be life-threatening, and thus
      have strong impact on both the development and marketing of drugs. Because the
      conventional biomarkers such as aspartate aminotransferase (AST), lactate
      dehydrogenase (LDH), and creatine kinase (CK) have low detection power, there has
      been increasing interest in developing biomarkers with higher detection power.
      The current study examined the usefulness of several promising biomarkers,
      cardiac and skeletal muscle troponins (cTnI, cTnT and sTnI), fatty acid binding
      protein 3 (FABP3) and myosin light chain 3 (MYL3), and compared the obtained data
      to AST, LDH and CK in rat models treated with various myotoxic and non-myotoxic
      compounds (isoproterenol, metaproterenol, doxorubicin, mitoxantrone, allylamine,
      cyclosporine A, cyclophosphamide, aminoglutethimide, acetaminophen,
      methapyrilene, allylalcohol and alpha-naphthylisothiocyanate). These promising
      biomarkers were found to be superior to the conventional biomarkers, as they had
      a specific and abundant distribution within the heart and/or skeletal muscles;
      exhibited a positive correlation between the amplitude of increases and the
      degree of pathological alterations; had higher diagnostic accuracy for detecting
      pathological alterations; and had the additive effect of improving the diagnostic
      accuracy of conventional biomarkers. However, these promising biomarkers have
      several drawbacks including a rapid clearance, the fact that they are affected by
      renal dysfunction, and different reactivity to the mode of action of individual
      myotoxicants. In conclusion, the promising biomarkers cTnI, cTnT, FABP3, MYL3,
      and sTnI demonstrated sensitivity and specificity for cardiac and skeletal
      myotoxicity that was superior to those of conventional biomarkers, while we
      should pay attention to the drawbacks of these biomarkers when used in toxicity
      studies.

PMID- 22878005
TI  - Contrast-enhanced 3T high-resolution MR imaging in symptomatic atherosclerotic
      basilar artery stenosis.
AB  - BACKGROUND AND PURPOSE: Contrast-enhanced 3T high-resolution MR imaging can be
      used to determine the wall enhancement pattern of the basilar artery in
      symptomatic atherosclerotic stenosis. We used this method to explore the
      relationship between wall enhancement and both recent infarction in the territory
      of the stenotic BA and subsequent ischemic events associated with the stenotic
      BA. MATERIALS AND METHODS: Sixty patients with symptomatic atherosclerotic BA
      stenosis >=70% were enrolled consecutively. HR-MRI of cross-sectional BAs was
      obtained before and after contrast media injection, and wall enhancement indices
      were calculated for sections proximal to, at, and distal to the site of maximal
      luminal narrowing. DWI of the brain was performed to determine the presence of
      recent infarction. RESULTS: Images from 56 patients were suitable for analysis.
      Thirty-three patients underwent stent placement for the stenotic BA, and 23
      patients underwent conservative medical treatment with antiplatelet agents and
      risk-factor control. All 23 patients with medical treatment had a 12-month follow
      up. Greater wall enhancement was seen in the section proximal to the MLN section
      in both patients with recent infarction (74 +/- 65% versus 44 +/- 44%; P = .046)
      and in patients with subsequent ischemic events (100 +/- 57% versus 44 +/- 44%; P
      = .014). CONCLUSIONS: Greater wall enhancement proximal to the MLN site
      correlates with recent infarction in the territory of the stenotic BA and
      subsequent ischemic events associated with the stenotic BA. Contrast-enhanced HR
      MRI may serve as a noninvasive tool for risk stratification of BA
      atherosclerosis.

PMID- 22878006
TI  - Quantitative MRI analysis of craniofacial bone marrow in patients with sickle
      cell disease.
AB  - BACKGROUND AND PURPOSE: Assessment of bone marrow is most commonly performed
      qualitatively in the spine or other large long bones. The craniofacial bones are
      less ideal for bone marrow analysis because of the relatively small bone marrow
      volume. Because patients with SCD often undergo repeated brain imaging to
      evaluate for cerebral vaso-occlusive disease, quantitative assessment of
      craniofacial bone marrow is a reasonable possibility in these patients. The
      purpose of this study was to investigate specific sickle cell disease changes in
      craniofacial bone marrow quantitatively by analyzing T1, T2, and secular-T2
      relaxation times and volume with the use of quantitative MRI. MATERIALS AND
      METHODS: Fourteen patients with SCD and 17 control subjects were imaged with the
      mixed TSE pulse sequence at 1.5T. The craniofacial bones were manually segmented
      by using 3D Slicer to generate bone marrow volumes and to provide T1, T2, and
      secular-T2 relaxation times. RESULTS: All subjects exhibited a bimodal T1
      histogram. In the SCD group, there was a decrease in amplitude in the first T1
      peak and an increase in amplitude in the second T1 peak. The first T1 peak showed
      a significant increase in relaxation time compared with control subjects (P <
      .0001), whereas there was no significant difference in the second T1 peak. T2 and
      secular-T2 relaxation times were significantly shorter in the SCD group (T2, P <
      .0001; secular-T2, P < .0001). Increasing numbers of blood transfusions resulted
      in a decrease in T2 and secular-T2 times. Patients with SCD exhibited a larger
      bone marrow volume compared with control subjects, even after standardization.
      CONCLUSIONS: Patients with SCD exhibited significant quantifiable changes in the
      craniofacial bone marrow because of failure of red-to-yellow marrow conversion
      and iron deposition that can be identified by qMRI relaxometry and volumetry.
      Both qMRI relaxometry and volumetry may be used as noninvasive tools for
      assessment of disease severity.

PMID- 22878007
TI  - The varying porosity of braided self-expanding stents and flow diverters: an
      experimental study.
AB  - BACKGROUND AND PURPOSE: Braided self-expandable stents and flow diverters of
      uniform construction may develop zones of heterogeneous porosity in vivo.
      Unwanted stenoses may also occur at the extremities of the device. We studied
      these phenomena in dedicated benchtop experiments. MATERIALS AND METHODS: Five
      braided devices of decreasing porosity were studied. To simulate discrepancies in
      diameters between the landing zones of the parent vessel and the aneurysm neck
      area, device extremities were inserted into silicone tubes of various diameters
      (2-3 mm), leaving the midportion free to react to experimental manipulations,
      which included axial approximation of the tubes (0-7 mm), and curvature (0-135
      degrees ), with or without axial compression (0-2 mm). The length of the landing
      zone was sequentially decreased to study terminal device stenosis. RESULTS: All
      devices adopted a conformation characterized by 3 different zones: bilateral
      landing zones, a middle compaction zone, and 2 transition zones. It is possible,
      during deployment, to compact stents and FDs to decrease porosity, but a limiting
      factor was the transition zone, which remained relatively unchanged and of higher
      porosity than the expansion zone. Length of the transition zone increased when
      devices were constrained in smaller tubes. Heterogeneities in porosity with
      compaction and curvatures were predictable and followed simple geometric rules.
      Extremity stenoses occurred increasingly with decreasing length of the landing
      zone. CONCLUSIONS: Braided self-expandable devices show predictable changes in
      porosity according to device size, vessel diameter, and curvature. Adequate
      landing zones are required to prevent terminal device stenosis.

PMID- 22878008
TI  - CT angiography for surgical planning in face transplantation candidates.
AB  - SUMMARY: Facial allotransplantation replaces missing facial structures with
      anatomically identical tissues, providing desired functional, esthetic, and
      psychosocial benefits far superior to those of conventional methods. On the basis
      of very encouraging initial results, it is likely that more procedures will be
      performed in the near future. Typical candidates have extremely complex vascular
      anatomy due to severe injury and/or multiple prior reconstructive attempts; thus,
      each procedure is uniquely determined by the defects and vascular anatomy of the
      candidate. We detail CT angiography vascular mapping, noting the clinical
      relevance of the imaging, the angiosome concept and noninvasive delineation of
      the key vessels, and current controversies related to the vascular anastomoses.

PMID- 22878009
TI  - Imaging of cosmetic facial implants and grafts.
AB  - SUMMARY: A wide variety of implants and grafts have been used for cosmetic facial
      surgery, including forehead, nose, cheek, lip, and chin augmentation. Some of the
      implant materials include silicone, expanded polytetrafluoroethylene (Gore-Tex),
      hydroxylapatite, and porous polyethylene (Medpor). Grafts include bone and
      cartilage, which can be prepared as "Turkish Delight" for rhinoplasty. Imaged
      facial implants and grafts can be encountered incidentally or purposely to
      evaluate complications. Many of these materials have distinct radiologic imaging
      features and should not be misinterpreted as pathology. Conversely, implant
      complications should be appropriately recognized by using a focused imaging
      approach. The purpose of this article was to review the different types of
      cosmetic facial implants and grafts with an emphasis on their expected and
      complicated radiologic imaging appearances.

PMID- 22878010
TI  - Cervical spine MR imaging findings of patients with Hirayama disease in North
      America: a multisite study.
AB  - BACKGROUND AND PURPOSE: Most studies of HD have been conducted in Asia,
      particularly Japan. To characterize the MR imaging findings of North American
      patients with HD, we reviewed neutral and flexion cervical MR imaging
      examinations performed for possible HD at 3 academic medical centers located in
      the Southeastern, Southwestern, and Midwestern regions of the United States.
      MATERIALS AND METHODS: Three neuroradiologists assessed the MR imaging
      examinations in a blinded fashion and reached a consensus rating for LOA of the
      posterior dura to the spine, lower spinal cord atrophy, spinal cord T2
      hyperintensity, loss of cervical lordosis, anterior dural shift with flexion, and
      confidence of imaging diagnosis. Final reference diagnosis was established
      separately with a retrospective chart review by a neurologist. RESULTS: Twenty
      one patients met the criteria for HD, all were North American males and all who
      reported their race were white. Seventeen patients did not meet the criteria and
      served as controls. Four imaging attributes, LOA, dural shift with flexion,
      consensus diagnosis of neutral images, and consensus diagnosis of combined
      neutral and flexion images were all able to discriminate the group with HD from
      the group without HD (P < .05 for each). Findings of HD were often present on
      neutral images, but the addition of flexion images increased diagnostic
      confidence. CONCLUSIONS: MR imaging findings in white North American patients
      with HD include LOA on neutral images and forward displacement of the dura with
      flexion. Findings are often present on neutral MR images and, in the appropriate
      clinical scenario, should prompt flexion MR imaging to evaluate anterior dural
      shift.

PMID- 22878011
TI  - Evaluation of an intravenous-endovascular strategy in patients with acute
      proximal middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: IVT administered in acute ischemic stroke provides low
      recanalization rates in proximal intracranial occlusions, with consequently poor
      clinical outcome. The safety and efficacy of an IES by using mechanical
      thrombectomy after IVT failure were assessed in acute MCA occlusions. MATERIALS
      AND METHODS: Patients presenting with acute MCA occlusion within 4.5 hours with
      an NIHSS score between 8 and 25 and a DWI ASPECTS of >5 were eligible. From
      September 2009 to September 2010, mechanical thrombectomy by using the Solitaire
      FR device was systematically performed if no clinical improvement was observed 1
      hour after the initiation of IVT (IES group). Results in terms of clinical
      outcome were compared with those from an IVT series from January 2007 to August
      2009 (IVT group). RESULTS: Alteplase was administered in 123 patients with
      proximal intracranial occlusion. Fifty-six had a confirmed MCA occlusion: 32 were
      included in the IVT group; and 24, in the IES group. At 24 hours, the median
      NIHSS improvement was 8.5 points in the IES group (25%-75% CI, 1.5-13) and 3
      points in the IVT group (25%-75% CI, 1-5) (P = .001). At 3 months, 17/22 (77%)
      patients from the IES group and 15/30 (50%) from the IVT group had an mRS score
      of <=2. After adjustment for confounding variables, IES was strongly associated
      with favorable clinical outcome (77% versus 50%; adjusted odds ratio = 11.9; 95%
      CI, 1.6-89.1; P < .02). No symptomatic intracranial hemorrhage was observed.
      CONCLUSIONS: IES by using systematic mechanical thrombectomy after IVT failure
      safely improves the clinical outcome at 3 months and could represent an
      interesting alternative in the management of patients with acute MCA occlusion.

PMID- 22878012
TI  - Classification of cerebral arteriovenous malformations and intranidal flow
      patterns by color-encoded 4D-hybrid-MRA.
AB  - BACKGROUND AND PURPOSE: 4D MRA has been evolving as a noninvasive supplement for
      DSA. The purpose of this study was to evaluate the feasibility of a newly
      developed blood flow visualization technique for the classification of cerebral
      AVMs. We hypothesized that 4D-hMRA allows detection of different flow patterns
      within the nidus as well as differentiation of feeders and draining veins and has
      very good agreement with DSA regarding the Spetzler-Martin grade. MATERIALS AND
      METHODS: Thirty-one consecutive patients with AVMs were evaluated by using 4D
      hMRA and DSA by 2 blinded raters. Rating criteria included Spetzler-Martin score
      and other morphologic variables together with a new scale for 3 intranidal flow
      patterns (homogeneous = 1, unidirectional = 2, heterogeneous = 3). RESULTS: The
      Spetzler-Martin grades were rated different from DSA in 5 cases by rater 1 and in
      3 cases by rater 2 with an excellent interrater reliability of kappa = 0.96
      (4/31, 1 by size and 3 by drainage). Each reader missed 5 feeders on 4D-hMRA.
      Draining veins were distinguished in the temporal course in 7 on DSA but in 8 and
      12 on 4D-hybrid-MRA (raters 1 and 2 respectively), with kappa = 0.79. A type 1
      intranidal flow pattern was recognizable in 9 (30%) patients; type 2, in 19
      (60%); and type 3, in 3 (10%). CONCLUSIONS: 4D-hMRA allows reliable Spetzler
      Martin grading and detection of brain arteriovenous malformation feeding arteries
      and draining veins, with the drawback that for small vessels DSA is still needed.
      Draining veins might even be detected with higher sensitivity than on DSA.
      Discrimination of different intranidal flow patterns is possible, but their
      relevance for hemorrhage risk assessment and therapy planning requires further
      study.

PMID- 22878013
TI  - Language lateralization represented by spatiotemporal mapping of
      magnetoencephalography.
AB  - BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is
      critical for planning epilepsy surgery. We assess the usefulness of
      spatiotemporal source analysis of magnetoencephalography for determining language
      laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were
      studied. The patients performed a semantic word-processing task during MEG
      recording. Epochs containing language-related neuromagnetic activity were
      averaged after preprocessing. The averaged data between 250 and 550 ms after
      stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were
      obtained in the opercular and triangular parts of the inferior frontal gyrus,
      superior temporal gyrus, and supramarginal gyrus in both hemispheres. We
      calculated laterality indices according to 1) dSPM-amplitude method, based on the
      amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the
      number of unit dipoles with activation over a threshold in the ROIs. The
      threshold was determined as half of the maximum value in all ROIs for each
      patient. A LI >=0.10 or <=-0.10 was considered left- or right-hemisphere
      dominance, respectively; a LI between -0.10 and 0.10 was considered bilateral.
      All patients underwent an intracarotid amobarbital procedure as part of
      presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality
      consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%)
      demonstrated bilateral language representation, whereas the dSPM-amplitude method
      showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to
      the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization
      with the dSPM-counting method may reduce the necessity for an IAP in as many as
      90% of patients.

PMID- 22878014
TI  - Acute alterations on DTI caused by alcohol consumption: region of interest-based
      diffusion tensor analysis limited because of poor reproducibility, with the
      additional detrimental effects of a small population size and minute changes.

PMID- 22878015
TI  - p38 MAP kinase and ERK play an important role in nitric oxide-induced apoptosis
      of the mouse embryonic stem cells.
AB  - Previous study showed that nitric oxide (NO) induces apoptosis in mouse embryonic
      stem (mES) cells, but the precise mechanism governing NO-induced apoptosis in mES
      remains unclear. This study investigated the mechanism of NO-induced apoptosis of
      mES cells via MAP kinase signaling pathway. Sodium nitroprusside (SNP), a NO
      donor, induced apoptosis in mES cells with enhanced production of reactive oxygen
      species (ROS). In addition, treatment with SNP induced the activation of caspase
      3, -8 and -9 as well as mitogen-activated protein (MAP) kinases (JNK, p38 MAP
      kinase and ERK). However, pretreatment with the p38 MAP kinase inhibitor SB203580
      and ERK inhibitor U0126 attenuated NO-induced cell toxicity, ROS production, and
      caspase-3 activation. Moreover, SB203580 inhibited the translocation of Bax from
      the cytosol to the mitochondria. Taken together, these results suggest that NO
      induced apoptosis in mES cells was mediated through p38 MAP kinase/ERK signaling
      pathway by triggering caspases activation and Bax translocation from the cytosol
      to the mitochondria.

PMID- 22878017
TI  - miR-21: a central regulator of fibrosis not only in the broken heart.

PMID- 22878020
TI  - Vitamin B or L-arginine supplementation in hyperhomocysteinaemia: think twice!

PMID- 22878021
TI  - TGFbeta3 mutations cause arrhythmogenic right ventricular dysplasia type 1 and
      open the door to understanding the biological role of TGFbeta3 (where there's a
      will, there's a way).

PMID- 22878022
TI  - A complete characterization of the vibrational spectra of sucrose.
AB  - We combined experimental vibrational spectroscopy (FTIR-Raman) and ab-initio
      calculations based on density functional theory (DFT) to predict the structural
      and vibrational properties of sucrose in solid phase. The structural properties
      of sucrose, such as the bond order, possible charge-transfer, and the topological
      properties of the glucopyran and glucofuran rings were studied by means of the
      Natural Bond Orbital (NBO) and Atoms in Molecules theory (AIM) investigation. For
      a complete assignment of the infrared and Raman spectra, the density functional
      theory (DFT) calculations were combined with Pulay's Scaled Quantum Mechanics
      Force Field (SQMFF) methodology in order to fit the theoretical frequency values
      to the experimental ones. An agreement between theoretical and available
      experimental results was found. A complete assignment of the 129 normal vibration
      modes for sucrose was performed. Five very intense characteristic bands in the
      infrared spectrum of sucrose at 3391, 3339, 1069, 1053, and 991 cm(-1) were
      assigned, the first two to the OH stretching modes while the other ones to C-O
      stretching modes.

PMID- 22878024
TI  - Dual sampling for STI research, prevention, and treatment.

PMID- 22878025
TI  - Health dialogues between pupils and school nurses: a description of the verbal
      interaction.
AB  - OBJECTIVE: The purpose of this study was to explore and describe the content of
      and the verbal interaction in health dialogues between pupils and school nurses.
      METHODS: Twenty-four health dialogues were recorded using a video camera and the
      conversations were analysed using the paediatric version of the Roter Interaction
      analysis system. RESULTS: The results showed that the age appropriate topics
      suggested by national recommendations were brought up in most of the health
      dialogues. The nurses were the ones who talked most, in terms of utterances. The
      pupils most frequently gave information about their lifestyle and agreed with the
      nurses' statements. The nurses summarised and checked that they had understood
      the pupils, asked closed-ended questions about lifestyle and gave information
      about lifestyle. Strategies aimed to make the pupil more active and participatory
      in the dialogues were the most widely used verbal interaction approaches by the
      nurses. CONCLUSION: The nurses' use of verbal interaction approaches to promote
      pupils' activity and participation, trying to build a partnership in the
      dialogue, could indicate an attempt to build patient-centred health dialogues.
      PRACTICE IMPLICATIONS: The nurses' great use of questions and being the ones
      leading the dialogues in terms of utterances point at the necessity for a nurses
      to have an openness to the pupils own narratives and an attentiveness to what he
      or she wants to talk about.

PMID- 22878023
TI  - Prevalences of sexually transmitted infections in young adults and female sex
      workers in Peru: a national population-based survey.
AB  - BACKGROUND: We assessed prevalences of seven sexually transmitted infections
      (STIs) in Peru, stratified by risk behaviours, to help to define care and
      prevention priorities. METHODS: In a 2002 household-based survey of the general
      population, we enrolled randomly selected 18-29-year-old residents of 24 cities
      with populations greater than 50 000 people. We then surveyed female sex workers
      (FSWs) in these cities. We gathered data for sexual behaviour; vaginal specimens
      or urine for nucleic acid amplification tests for Neisseria gonorrhoeae,
      Chlamydia trachomatis, and Trichomonas vaginalis; and blood for serological tests
      for syphilis, HIV, and (in subsamples) herpes simplex virus 2 (HSV2) and human T
      lymphotropic virus. This study is a registered component of the PREVEN trial,
      number ISRCTN43722548. FINDINGS: 15 261 individuals from the general population
      and 4485 FSWs agreed to participate in our survey. Overall prevalence of
      infection with HSV2, weighted for city size, was 13.5% in men, 13.6% in women,
      and 60.6% in FSWs (all values in FSWs standardised to age composition of women in
      the general population). The prevalence of C trachomatis infection was 4.2% in
      men, 6.5% in women, and 16.4% in FSWs; of T vaginalis infection was 0.3% in men,
      4.9% in women, and 7.9% in FSWs; and of syphilis was 0.5% in men, 0.4% in women,
      and 0.8% in FSWs. N gonorrhoeae infection had a prevalence of 0.1% in men and
      women, and of 1.6% in FSWs. Prevalence of HIV infection was 0.5% in men and FSWs,
      and 0.1% in women. Four (0.3%) of 1535 specimens were positive for human T
      lymphotropic virus 1. In men, 65.0% of infections with HIV, 71.5% of N
      gonorrhoeae, and 41.4% of HSV2 and 60.9% of cases of syphilis were in the 13.3%
      who had sex with men or unprotected sex with FSWs in the past year. In women from
      the general population, 66.7% of infections with HIV and 16.7% of cases of
      syphilis were accounted for by the 4.4% who had been paid for sex by any of their
      past three partners. INTERPRETATION: Defining of high-risk groups could guide
      targeting of interventions for communicable diseases-including STIs-in the
      general Peruvian population. FUNDING: Wellcome Trust-Burroughs Wellcome Fund
      Infectious Disease Initiative and US National Institutes of Health.

PMID- 22878026
TI  - Disremembering the holocaust.
AB  - The essay describes an elderly Holocaust survivor, who re-experiences the horrors
      of the Holocaust through his senile hallucinations. Although he is demented,
      telling and re-telling the story to a therapist helps him regain a sense of
      control and feel less frightened. He is finally able to revise the nightmarish
      story into a narrative that enables him to find strength and meaning.

PMID- 22878027
TI  - Educating health consumers about cardio-metabolic health risk: what can we learn
      from lay mental models of risk?
AB  - OBJECTIVE: To study lay conceptions of cardio-metabolic risk and compare them
      with those of experts, in order to formulate focal points for better educational
      risk information. METHODS: 40 Dutch lay people were interviewed about the risks
      of developing cardio-metabolic diseases. Following a 'mental models approach',
      their conceptions were qualitatively analyzed and compared to an expert model.
      RESULTS: We identified four key themes representing lay conceptions: (1) "same
      factors, different value" (e.g. the dominance of certain factors, such as
      stress); (2) "superficiality and incoherence" (e.g. a focus on health and illness
      in general); (3) "misjudged elevated risk concept" (e.g. either being sick or
      not); and (4) "no concept of a link between cardio-metabolic diseases" (e.g.
      separate links between causes and diseases). CONCLUSION: Potential mismatches
      between lay and expert conceptions do not seem to indicate a lack of basic
      knowledge among consumers, but rather that certain risk factors are not
      effectively translated into a coherent risk picture. PRACTICE IMPLICATIONS: In
      improving educational materials, we could more explicitly take into account
      factors that lay people find important. Additionally, effort should be made to
      produce a more coherent risk understanding among consumers, for example through
      an alternative information structure.

PMID- 22878028
TI  - Communication-related behavior change techniques used in face-to-face lifestyle
      interventions in primary care: a systematic review of the literature.
AB  - OBJECTIVES: To systematically review the literature on the relative effectiveness
      of face-to-face communication-related behavior change techniques (BCTs) provided
      in primary care by either physicians or nurses to intervene on patients'
      lifestyle behavior. METHODS: PubMed, EMBASE, PsychINFO, CINAHL and The Cochrane
      Library were searched for studies published before October 2010. Fifty studies
      were included and assessed on methodological quality. RESULTS: Twenty-eight
      studies reported significantly favorable health outcomes following communication
      related BCTs. In these studies, 'behavioral counseling' was most frequently used
      (15 times), followed by motivational interviewing (eight times), education and
      advice (both seven times). Physicians and nurses seem equally capable of
      providing face-to-face communication-related BCTs in primary care. CONCLUSION:
      Behavioral counseling, motivational interviewing, education and advice all seem
      effective communication-related BCTs. However, BCTs were also found in less
      successful studies. Furthermore, based on existing literature, one primary care
      profession does not seem better equipped than the other to provide face-to-face
      communication-related BCTs. PRACTICE IMPLICATIONS: There is evidence that
      behavioral counseling, motivational interviewing, education and advice can be
      used as effective communication-related BCTs by physicians and nurses. However,
      further research is needed to examine the underlying working mechanisms of
      communication-related BCTs, and whether they meet the requirements of patients
      and primary care providers.

PMID- 22878029
TI  - Development and content of a group-based intervention to improve medication
      adherence in non-adherent patients with rheumatoid arthritis.
AB  - OBJECTIVE: To describe the systematic development and content of a short
      intervention to improve medication adherence to disease-modifying anti-rheumatic
      drugs in non-adherent patients with rheumatoid arthritis (RA). METHODS: The
      intervention mapping (IM) framework was used to develop the intervention. The
      following IM steps were conducted: (1) a needs assessment; (2) formulation of
      specific intervention objectives; (3) inventory of methods and techniques needed
      to design the intervention and (4) production and piloting of the intervention.
      RESULTS: The intervention (consisting of two group sessions led by a pharmacist,
      a homework assignment, and a follow-up call) aims to improve the balance between
      necessity and concern beliefs about medication, and to resolve practical barriers
      in medication taking. The central communication method used is motivational
      interviewing. CONCLUSION: By applying the IM framework, we were able to create a
      feasible, time-efficient and promising intervention to improve medication
      adherence in non-adherent RA patients. Intervention effects are currently being
      assessed in a randomized controlled trial. PRACTICE IMPLICATIONS: This paper
      could serve as a guideline for other health care professionals when developing
      similar interventions. If the RCT demonstrates sufficient effectiveness of this
      intervention in reducing medication non-adherence in RA patients, the
      intervention could be embedded in clinical practice.

PMID- 22878031
TI  - The DNA methylation profile of PLA2G4C gene promoter in schizophrenia.

PMID- 22878030
TI  - Validation of the Dutch functional, communicative and critical health literacy
      scales.
AB  - OBJECTIVE: While most existing health literacy (HL) measures focus primarily on
      reading comprehension, the functional, communicative and critical HL scales from
      Ishikawa et al. [19] aim to measure a broader HL spectrum. The objective of this
      study was to evaluate the validity of the Dutch translation of this instrument.
      METHODS: Two survey studies (n = 79 and n = 209) and one cognitive interview
      study (n = 18) were performed among samples of breast cancer patients and
      patients with rheumatic diseases. RESULTS: Analyses showed the scales measured
      three distinct factors and convergent validity was satisfactory for communicative
      and critical HL. Nevertheless, the comprehension of the items and the suitability
      of the response options raised some problems. CONCLUSION: The HL scales seem
      promising to measure a broad definition of HL. By revising some of the items and
      response options as proposed in this article, the scale will become more
      understandable for people with low HL skills, which might increase the content
      validity and the distributional properties of the scale. PRACTICE IMPLICATIONS:
      The scale should be revised and revalidated. An improved version should be used
      in practice to gain insight into HL levels of patients. This will help to develop
      suitable education programs for people with low HL skills.

PMID- 22878032
TI  - Childhood physical abuse as a common risk factor for depression and thyroid
      dysfunction in the earlier postpartum.
AB  - Childhood abuse is a powerful risk factor for developing postpartum depression in
      adulthood, and recently it has been associated to thyroid dysfunction in
      postpartum depressive women. The purpose of this study was to investigated the
      effects of childhood abuse on thyroid status and depressive symptomatology in two
      hundred and thirty-six (n=236) postpartum women 24-48h after delivery. The Early
      Trauma-Inventory Self-Report was used to assess the presence of childhood abuse
      and the Edinburgh Postpartum Depression Scale (EPDS) to evaluate depressive
      symptomatology (EPDS>=11). Free thyroxin (fT4) and thyroid-stimulating hormone
      (TSH) were measured. Thyroid dysfunction (TD) was defined as altered TSH or TSH
      and fT4. Socio-demographic, reproductive, and psychopathological variables were
      also collected. Multivariate analysis shows that childhood physical abuse
      increases by four times the risk for TD (OR: 3.95, 95% CI: 1.23-12.71) and five
      times the risk for depressive symptomatology (OR: 5.45, 95% CI: 2.17-13.66) in
      the earlier postpartum. Our findings suggest that women with history of childhood
      physical abuse are particularly at-risk for thyroid dysfunction and depressive
      symptomatology 24-48h after delivery. The assessment of childhood abuse in the
      perinatal period is important to identify women at-risk for physical and mental
      health problems in this period.

PMID- 22878033
TI  - Proteomic identification of quality factors for oocytes in the Pacific oyster
      Crassostrea gigas.
AB  - We used a 2-DE proteomic approach to identify abundant proteins linked to oocyte
      quality in the Pacific oyster Crassostrea gigas, an economically important
      bivalve. Oocyte quality of 14 females was estimated by recording fertilisation
      and early developmental success until D-larval stage under controlled conditions.
      Proteins that were differentially expressed between females showing high or low
      oocyte quality were identified by nano-liquid chromatography tandem mass
      spectrometry. Twelve up-accumulated spots associated with low quality oocytes
      revealed 10 distinct proteins, including vitellogenin - breakdown products and
      metabolic enzymes. Eight up-accumulated spots from high quality oocytes revealed
      6 distinct proteins, including chaperone molecules and cell-cycle control
      proteins. This is the first proteomic study dedicated to oocytes in C. gigas. Our
      results improve current knowledge about protein factors associated with oocyte
      quality in this species, and our understanding of the proteomic processes
      involved in their developmental competence.

PMID- 22878034
TI  - [Review of genetic research and testing in sport].
AB  - There is compelling evidence for a genetic contribution to physical performance.
      In addition, there is an advanced scientific knowledge on the predisposition to
      sports-related diseases and injuries. Genetic testing of performance related
      polymorphisms can serve as a new opportunity for developing the process of talent
      selection. Sport-related genetic information may also allow for individualization
      of the training and improve performance. Genetic testing may also play an
      important role in the pre-participation screening for injuries and disease risks.

PMID- 22878035
TI  - [Aortic valve stenosis is associated with reduced myocardial perfusion as
      assessed by videodensitometry in coronary angiograms].
AB  - Aortic valve stenosis may be accompanied by angina despite coronary arteries free
      of significant stenosis due to microvascular abnormalities. AIMS: The aim of the
      current study was to test whether densitometry-derived myocardial perfusion on
      coronary angiogram is reduced in patients with aortic valve stenosis. METHODS:
      The study comprised 20 patients with aortic valve stenosis (mean transvalvular
      gradient: 47.4+/-15.2 mm Hg) and 30 control subjects without significant
      epicardial coronary artery stenosis. A quantitative parameter of myocardial
      perfusion was calculated by the ratio of maximal density (Gmax) and time to reach
      maximum density (Tmax) on time-density curves in regions of interest of each
      coronary artery on coronary angiograms. RESULTS: Mean three-vessel Gmax/Tmax
      proved to be significantly lower in patients with aortic valve stenosis compared
      to control subjects (2.55+/-1.02 1/sec vs. 3.39+/-1.09 1/sec, p<0.01).
      CONCLUSIONS: Reduced Gmax/Tmax values indicative of myocardial perfusion
      abnormalities as measured by densitometry on coronary angiograms could be
      demonstrated in patients with aortic valve stenosis compared to controls.

PMID- 22878036
TI  - [Investigation of the frequency of alcohol related problems in Jozsefvaros,
      Budapest. Data and conclusions of three surveys conducted among doctors and
      outpatients].
AB  - The role of permanent alcohol consumption in the development of diseases is well
      known. AIMS: To study the occurrence of alcohol related problems among patients
      of a municipal pulmonology out-patient clinic as well as in the family practice
      of three physicians. In addition, a survey was performed among physicians of a
      municipal health service and also among family practitioners working in the same
      district by investigating health problems, habits and professional careers of
      physicians, and their addictive problems, their attitude toward addict patients
      and their opinion upon chemical dependency. METHODS: CAGE-test was used to
      examine the presence of alcohol problem and a questionnaire was constructed for
      the study undertaken among physicians. RESULTS: The response rate was 60.18% and
      32.98% among patients who visited the pulmonology out-patient clinic and their
      family physician, respectively. Among those who responded to the test, as many as
      6.02% and 4.82% of the cases would need a further medical examination to make
      clear whether alcohol related health problem was present or not, whilst 9.77% and
      11.67% of the patients proved to be alcohol dependent, respectively. The response
      rate in the survey among physicians was 41.28%. As stated, physicians not only
      screen the patients for alcohol and drug dependence, but also refer them to a
      specialist. The general experience seems to oppose this statement. The majority
      of health professionals considered chemical dependence as a chronic disease,
      whereas a kind of moral judgment of the problem was also seen, particularly among
      family physicians. If they had the opportunity to choose whom to treat: an
      alcoholic or a drug dependent patient, the majority of them would treat patients
      brought under the first category. The CAGE test revealed alcohol problem in three
      family physicians, but none in specialists. Nearly all physicians consumed
      coffee, but the majority of them were non-smokers. As the risk for committing
      suicide is higher among physicians than in the general population, physicians
      were interviewed in this regard, too. Three physicians in the sample reported an
      attempt of suicide, and eleven physicians had suicidal ideas in the past.
      Although the majority of physicians were satisfied with their physical and mental
      health, several of them had serious health problems or were treated for
      depression. At the same time, the majority of physicians were unsatisfied with
      their financial and professional respect, and had the opinion that a career is
      unlikely to depend on the professional knowledge. DISCUSSION: Although the
      relatively low rate of physicians answering the questions did not make it
      possible to reveal the interrelationships among different variables, the study
      was able to direct the attention to the risk existing among physicians to commit
      suicide or use chemical substances. A proposal is made to establish an effective,
      but discreet and easy way to acquire psychiatric-addictological support. To avoid
      mental health problems among professionals working in psychiatry, organization of
      groups headed by someone not belonging to the same institute would be much
      encouraged. Parallel to these, the requirements and the conditions of making a
      career have to be made clear. On the basis of these surveys, as well as
      literature data, a continuous test examination of alcohol problem is recommended
      in the practice of family physicians as well as in the out-patient clinic of such
      disciplines like pulmonology and gastroenterology.

PMID- 22878037
TI  - [Ramsay Hunt syndrome].
AB  - Ramsay Hunt syndrome is a special form of herpes zoster which is typically
      characterized by peripheral facial palsy and unilateral herpetic vesicles on the
      ear. These symptoms are often accompanied by vestibulocochlear dysfunction and
      other neurological and ophthalmological symptoms. The diagnosis and therapy
      requires a multidisciplinary approach. The authors present a typical case where
      the early administration of combined antiviral and systemic corticosteroid
      therapy led to complete recovery. The authors emphasize the importance of early
      diagnosis and adequate combination therapy, which improves the prognosis of this
      disease.

PMID- 22878039
TI  - Alcohol: signs of improvement. The 2nd national Emergency Department survey of
      alcohol identification and intervention activity.
AB  - OBJECTIVES: To conduct a survey of current alcohol identification and brief
      advice activity in English Emergency Departments, and to compare the results with
      the previous survey conducted in 2007. METHODOLOGY: Cross-sectional survey of all
      187 Emergency Departments in England. RESULTS: Significant increases (p<0.001) in
      the proportion of departments routinely asking about alcohol, using a screening
      questionnaire, offering help/advice for alcohol problems, and having access to
      Alcohol Health Workers or Clinical Nurse Specialists. More than half of all
      departments indicated that they had an 'alcohol champion', and this was
      significantly associated with access to training on both identification and
      provision of brief advice (p<0.001). Departments that routinely asked questions
      were the most likely to use a formal screening tool (p<0.05), and the Paddington
      Alcohol Test was the most frequently used measure (40.5%). CONCLUSIONS: There
      have been significant improvements in ED alcohol identification and brief advice
      activity since 2007 in line with the recommendations of the Royal College of
      Physicians, Department of Health and NICE guidelines. English EDs are beginning
      to maximise the likelihood of identifying patients who may benefit from further
      help or advice about their alcohol consumption, and are able to offer access to
      specialist staff who can provide appropriate interventions.

PMID- 22878040
TI  - Satisfaction with the humanitarian response to the 2010 Pakistan floods: a call
      for increased accountability to beneficiaries.
AB  - OBJECTIVE: Ascertain recipients' level of satisfaction with humanitarian response
      efforts. DESIGN: A multi-stage, 80*20 cluster sample randomized survey (1800
      households) with probability proportional to size of households affected by the
      2010 Indus river floods in Pakistan. The floods affected over 18 million
      households and led to more than 8 billion USD in response dollars. RESULTS: Less
      than 20% of respondents reported being satisfied with response, though a small
      increase in satisfaction levels was observed over the three time periods of
      interest. Within the first month, receipt of hygiene items, food and household
      items was most strongly predictive of overall satisfaction. At 6 months, positive
      receipt of medicines was also highly predictive of satisfaction. The proportion
      of households reporting unmet needs remained elevated throughout the 6-month
      period following the floods and varied from 50% to 80%. Needs were best met
      between 1 and 3 months postflood, when response was at its peak. Unmet needs were
      the greatest at 6 months, when response was being phased down. CONCLUSIONS:
      Access-limiting issues were rarely captured during routine monitoring and
      evaluation efforts and seem to be a significant predictor in dissatisfaction with
      relief efforts, at least in the case of Pakistan, another argument in favor of
      independent, population-based surveys of this kind. There is also need to better
      identify and serve those not residing in camps. Direct surveys of the affected
      population can be used operationally to assess ongoing needs, more appropriately
      redirect humanitarian resources, and ultimately, judge the overall quality of a
      humanitarian response.

PMID- 22878041
TI  - Differential effect of age on the brain fatty acid levels and their  correlation
      with animal cognitive status in mice.
AB  - The aim of the present study was to investigate the possible relationship between
      the levels of various fatty acids (FA) in the brain and learning indices in aged
      (22-23 months old) and young (2-3 months old) female Swiss Webster (SW) mice. The
      mice were classified as "good" or "poor" learners based on their performance in a
      spatial learning task: the Morris Water Maze. The levels of several FA including
      palmitic, stearic, oleic, linoleic, arachidonic (AA), and docosahexaenoic acid
      (DHA), were measured by gas chromatography in tissue samples from four different
      brain areas: hippocampus, frontal cortex, striatum and hypothalamus. The results
      of behavioral tests confirmed a decline in learning skills with age. However, a
      great individual variation was revealed in learning scores between aged subjects,
      indicating that biological aging does not always parallel chronological aging.
      The relative levels of particular fatty acids across the four examined brain
      structures were very similar. Interestingly, only in the hypothalamus was the DHA
      omega-3 acid level significantly higher in young mice compared to the old mice.
      For the remaining brain structures, no significant correlations were found
      between the DHA level and the animal's age and/or cognitive status. A significant
      correlation between learning performance and fatty acid levels in the brain was
      found only for AA in the young mice hippocampus, a structure known to be critical
      for spatial learning and memory. The AA level was significantly lower in young
      "good" learners compared to both young "poor" and old "good" learners with young
      "good" learners showing significantly better performance than the two other
      groups. These findings contribute to the current debate on the value of DHA
      supplementation as an effective protective treatment against senile dementia and
      the potential role of AA in memory deficits.

PMID- 22878042
TI  - Montelukast potentiates the protective effect of rofecoxib against  kainic acid
      induced cognitive dysfunction in rats.
AB  - There is an evolving consensus that mild cognitive impairment (MCI) serves as a
      prodrome to Alzheimer's disease. Antioxidants and COX-2 (cyclo-oxygenase-2)
      inhibitors have also been reported to have beneficial effects against conditions
      of memory impairment. Newer drugs like cysteinyl leukotriene inhibitors have
      shown neuroprotective effect in animal models of ischemia. Thus, the present
      study purports to explore the potential role of montelukast (a cysteinyl
      leukotriene inhibitor) in concert with rofecoxib (COX-2 inhibitor) and caffeic
      acid (a 5-LOX inhibitor and potent antioxidant) against kainic acid induced
      cognitive dysfunction in rats. In the experimental protocol, kainic acid (0.4
      MUg/2 MUl) in artificial cerebrospinal fluid (ACSF) was given intrahippocampally
      (CA3 region) to induce a condition similar to MCI. Memory performance was
      measured on days 10-14 and the locomotor activity was measured on days 1, 7 and
      14. For estimation of biochemical, mitochondrial and histopathological
      parameters, animals were sacrificed on day 14, stored at -80  degrees C and the
      estimation was done on the 15th day. The treatment groups consisting of
      montelukast (0.5 and 1 mg/kg), rofecoxib (5 and 10 mg/kg) and caffeic acid (5 and
      10 mg/kg) showed significant improvement in memory performance, oxidative stress
      parameters and mitochondrial function as compared to that of control (kainic acid
      treated), however, combination of montelukast with rofecoxib showed significant
      improvement in their protective effect. Thus the present study emphasizes the
      positive modulation of cysteinyl leukotriene receptor inhibition on COX
      (cyclooxygenase) and LOX (lipoxygenase) pathways in the control of the
      neuroinflammation in kainic acid induced cognitive dysfunction in rats.

PMID- 22878044
TI  - IL-1beta and TSH disturb thyroid epithelium integrity in autoimmune thyroid
      diseases.
AB  - Pro-inflammatory cytokines such as IL-1beta and TNFalpha are known to affect
      thyroid function. They stimulate IL-6 secretion and modify epithelium integrity
      by altering junction proteins. To study the role of cytokines on thyroid
      epithelia tightness in autoimmune thyroid diseases (AITD), we analyzed the
      expression profiles of junction proteins (ZO-1, Claudin, JAM-A) and cytokines in
      human thyroid slices and also investigated the effect of IL-1beta on the
      epithelium integrity in primary cultures of human thyrocytes. Junction proteins
      expression (ZO-1, Claudin, JAM-A) has been analyzed by immunohistochemistry on
      thyroid slices and by Western blot on membrane proteins extracted from thyrocytes
      of patients suffering from Graves and Hashimoto diseases. The high expression of
      junction proteins we found on Graves' disease thyroid slices as well as in cell
      membrane extracts acknowledges the tightness of thyroid follicular cells in this
      AITD. In contrast, the reduced expression of JAM and ZO-1 in thyroid cells from
      patients suffering from Hashimoto thyroiditis is in agreement with the loss of
      thyroid follicular cell integrity that occurs in this pathology. Concerning the
      effects on epithelium integrity of TSH and of the pro-inflammatory cytokine IL
      1beta in primary cultures of human thyroid cells, TSH appeared able to modify JAM
      A localization but without any change in the expression levels of JAM-A, Claudin
      and ZO-1. Inversely, IL-1beta provoked a decrease in the expression of- and a
      redistribution of both, Claudin and ZO-1 without modifying the expression and sub
      cellular distribution patterns of JAM-A in thyroid cells. These results
      demonstrate (i) that Hashimoto's- and Graves' diseases display different junction
      proteins expression patterns with a loss of epithelium integrity in the former
      and (ii) that IL-1beta modifies thyroid epithelial tightness of human thyrocytes
      by altering the expression and localization of junction proteins. Therefore, IL
      1beta could play a role in the pathogenesis of thyroid autoimmunity.

PMID- 22878045
TI  - Part one: for the motion. Lower extremity bypass versus endovascular therapy for
      young patients with symptomatic peripheral arterial disease.

PMID- 22878046
TI  - Part two: against the motion. endovascular therapy is the preferred treatment for
      patients <65 years old with symptomatic infrainguinal arterial disease.

PMID- 22878047
TI  - Protein kinase C signaling molecules regulate encystation of Acanthamoeba.
AB  - Protein kinase C (PKC) is involved in receptor desensitization, membrane
      biogenesis, transcription regulation, immune response mediation, and cell growth
      regulation. Results of ESTs analysis and microarray analysis of Acanthamoeba
      cysts revealed high expression of PKC during encystation of Acanthamoeba. PKC
      inhibitor, chelerythrine chloride, inhibited cyst maturation of Acanthamoeba.
      Through domain search analysis, we found 27 types of PKC genes from Acanthamoeba
      ESTs (AcPKC1-AcPKC27), all of which were defined as atypical PKC isoforms.
      Results of fluorescence microscopic analysis showed the localization of AcPKC in
      cell membranes or nuclear membranes during encystation. siRNA against AcPKC
      reduced the encystation efficiency of Acanthamoeba. These AcPKC may be involved
      in several signal transduction pathways, especially during encystation of
      Acanthamoeba.

PMID- 22878048
TI  - Two-year performance by evapotranspiration covers for municipal solid waste
      landfills in northwest Ohio.
AB  - Evapotranspiration (ET) covers have gained interest as an alternative to
      conventional covers for the closure of municipal solid waste (MSW) landfills
      because they are less costly to construct and are expected to have a longer
      service life. Whereas ET covers have gained acceptance in arid and semi-arid
      regions (defined by a precipitation (P) to potential evapotranspiration (PET)
      ratio less than 0.75) by meeting performance standards (e.g. rate of
      percolation), it remains unclear whether they are suitable for humid regions
      (P:PET greater than 0.75). The goal of this project is to extend their
      application to northwest Ohio (P:PET equals 1.29) by designing covers that
      produce a rate of percolation less than 32 cm yr(-1), the maximum acceptable rate
      by the Ohio Environmental Protection Agency (OEPA). Test ET covers were
      constructed in drainage lysimeters (1.52 m diameter, 1.52 m depth) using dredged
      sediment amended with organic material and consisted of immature (I, plants
      seeded onto soil) or mature (M, plants transferred from a restored tall-grass
      prairie) plant mixtures. The water balance for the ET covers was monitored from
      June 2009 to June 2011, which included measured precipitation and percolation,
      and estimated soil water storage and evapotranspiration. Precipitation was
      applied at a rate of 94 cm yr(-1) in the first year and at rate of 69 cm yr(-1)
      in the second year. During the first year, covers with the M plant mixture
      produced noticeably less percolation (4 cm) than covers with the I plant mixture
      (17 cm). However, during the second year, covers with the M plant mixture
      produced considerably more percolation (10 cm) than covers with the I plant
      mixture (3 cm). This is likely due to a decrease in the aboveground biomass for
      the M plant mixture from year 1 (1008 g m(-2)) to year 2 (794 g m(-2)) and an
      increase for the I plant mixture from year 1 (644 g m(-2)) to year 2 (1314 gm(
      2)). Over the 2-year period, the mean annual rates of percolation for the covers
      with the M and I plant mixtures were 7 and 8 cm yr(-1), which are below the OEPA
      standard. The results suggest the application of ET covers be extended to
      northwest Ohio and other humid regions.

PMID- 22878049
TI  - RecoPhos: full-scale fertilizer production from sewage sludge ash.
AB  - The substitution potential of sewage sludge for German primary phosphate imports
      has been estimated as 40%. Yet, a marketable option for the full scale recovery
      has been lacking. This study focuses on a full-scale process for the manufacture
      of a P-fertilizer from sewage sludge ash (SSA) adapted from the production of
      Triple Superphosphate. Given (i) conformity of the input with phosphate ores
      mined from sedimentary deposits, (ii) comparability of the product with a
      commercially available P-fertilizer regarding contaminant levels, P-fractionation
      and yield effects, and (iii) compliance of the output with the German Fertilizer
      Ordinance the RecoPhos P 38 fertilizer was discharged from the waste legislation
      regime. The fertilizer is currently being produced at a rate of 1000 tonnes per
      month and sold at a competitive price.

PMID- 22878050
TI  - The pitcher plant flesh fly exhibits a mixture of patchy and metapopulation
      attributes.
AB  - We investigated the pattern of spatial genetic structure and the extent of gene
      flow in the pitcher plant flesh fly Fletcherimyia fletcheri, the largest member
      of the inquiline community of the purple pitcher plant Sarracenia purpurea. Using
      microsatellite loci, we tested the theoretical predictions of different
      hypothesized population models (patchy population, metapopulation, or isolated
      populations) among 11 bogs in Algonquin Provincial Park (Canada). Our results
      revealed that the pitcher plant flesh fly exhibits a mixture of patchy and
      metapopulation characteristics. There is significant differentiation among bogs
      and limited gene flow at larger spatial scales, but local populations do not
      experience frequent local extinctions/recolonizations. Our findings suggest a
      strong dispersal ability and stable population sizes in F. fletcheri, providing
      novel insights into the ecology of this member of a unique ecological microcosm.

PMID- 22878051
TI  - Innovations and trends in meat consumption: an application of the Delphi method
      in Spain.
AB  - The meat sector in Spain is an important industry. However, traditional
      consumption is changing as a result of the country's economic crisis and the new
      structure of households. The objective of the present study was to identify
      trends in meat consumption in Spain extrapolated to 2016, and the main
      innovations that should be of interest to firms in the sector. The study was
      conducted in 2011 using the Delphi method with the participation of 26 experts.
      The results showed that, while the demand for meat will not vary significantly in
      amount, it will do so in composition, with chicken replacing beef as the meat of
      most importance in the shopping basket. In addition, significant growth is
      expected in certified meat, but the demand for organic meat will not take off.
      Neither will there be no significant changes in end purchase formats, but there
      will be a clear trend in consumers' purchasing decision criteria away from price,
      external appearance and origin towards quality certification and the attributes
      of the packaging. With respect to end purchase channels, the experts estimate
      that the current trend will be accentuated with increasing market share for large
      supermarkets and major distribution brands.

PMID- 22878052
TI  - So many doggone traits: mapping genetics of multiple phenotypes in the domestic
      dog.
AB  - The worldwide dog population is fragmented into >350 domestic breeds. Breeds
      share a common ancestor, the gray wolf. The intense artificial selection imposed
      by humans to develop breeds with particular behaviors and phenotypic traits has
      occurred primarily in the last 200-300 years. As a result, the number of genes
      controlling the major differences in body size, leg length, head shape, etc. that
      define each dog is small, and genetically tractable. This is in comparison to
      many human complex traits where small amounts of variance are controlled by
      literally hundreds of genes. We have been interested in disentangling the genetic
      mechanisms controlling breed-defining morphological traits in the domestic dog.
      The structure of the dog population, comprised large numbers of pure breeding
      populations, makes this task surprisingly doable. In this review, we summarize
      recent work on the genetics of body size, leg length and skull shape, while
      setting the stage for tackling other traits. It is our expectation that these
      results will contribute to a better understanding of mammalian developmental
      processes overall.

PMID- 22878053
TI  - Pathological and aetiological studies in sheep exhibiting extrathoracic
      metastasis of ovine pulmonary adenocarcinoma (Jaagsiekte).
AB  - Seven sheep with a histopathological diagnosis of pulmonary adenocarcinoma with
      extrathoracic metastases were included in this retrospective study aiming to
      describe the pathological findings and to establish their relationship with
      Jaagsiekte sheep retrovirus (JSRV). In order of frequency, extrathoracic
      metastases were found in the liver, kidneys, skeletal muscle, digestive tract,
      spleen, skin and adrenal glands. Intrathoracic metastases involved the chest
      wall, regional lymph nodes, diaphragm and heart. Immunohistochemistry and
      polymerase chain reaction allowed detection of JSRV-related protein and nucleic
      acid, respectively, in the extrathoracic tumours of all cases. It is concluded
      that extrathoracic metastases constitute a pathological event of ovine pulmonary
      adenocarcinoma and confirm the malignant character of this virus-induced
      neoplasia.

PMID- 22878054
TI  - GM2 gangliosidosis in an adult pet rabbit.
AB  - A 1.5-year-old neutered male rabbit was presented with chronic nasal discharge
      and ataxia. Rapid progression of neurological signs was noted subsequent to
      general anaesthesia and the rabbit was humanely destroyed due to the poor
      prognosis. At necropsy examination there were no gross changes affecting the
      brain or spinal cord. Microscopical examination revealed that the perikarya of
      numerous neurons in the brain and spinal cord were distended by the
      intracytoplasmic accumulation of pale, finely granular to vacuolar material.
      Transmission electron microscopy showed this to be composed of concentric
      membranous cytoplasmic bodies. Thin layer chromatography revealed elevation of
      GM2 ganglioside in the brain of this rabbit compared with that of an unaffected
      control rabbit. Enzymatically, there was markedly reduced activity of tissue beta
      hexosaminidase A in brain and liver tissue from the rabbit. This was a result of
      an almost complete absence of the enzymatic activity of the alpha-subunit of that
      enzyme. These findings are consistent with sphingolipidosis comparable with human
      GM2 gangliosidosis variant B1.

PMID- 22878055
TI  - Primary ovarian rhabdomyosarcoma in a dog.
AB  - A 10-year-old female English pointer was diagnosed with an ovarian tumour with
      abdominal metastases. Ultrasonography revealed several nodules of 1-5 cm diameter
      within the abdominal cavity. Fine needle aspiration cytology of the nodules
      suggested a malignant mesenchymal tumour. On necropsy examination the right ovary
      and its capsule were enlarged and there were white-red, friable nodular masses
      distributed over the surface of the pancreas, liver, omentum, mesentery and
      serosae of the small and large intestines. Microscopical evaluation revealed
      neoplastic cells with a high degree of pleomorphism and vascular invasion.
      Immunohistochemically, the neoplastic cells expressed myosin, desmin, vimentin
      and CD10, but were negative for cytokeratin, placental alkaline phosphatase,
      inhibin-alpha and smooth muscle actin. Based on these findings a diagnosis of
      primary ovarian alveolar rhabdomyosarcoma was made.

PMID- 22878056
TI  - Retrospective study of Mycoplasma gallisepticum meningoencephalitis in six turkey
      flocks in western France.
AB  - Mycoplasma gallisepticum (MG) meningoencephalitis was diagnosed in six turkey
      flocks, from 1998 to 2005, in the western part of France. Affected birds were 8
      11 weeks old and all displayed neurological signs, especially torticollis, with
      more than half having concomitant respiratory signs. Microscopical examination of
      brain samples from birds in all six flocks revealed similar lesions of acute to
      subacute multifocal parenchymal necrosis, perivascular cuffing, leptomeningitis
      and vasculitis. Birds from four of the six affected flocks were seropositive for
      MG and in birds from four flocks MG DNA was detected by polymerase chain reaction
      performed on tracheal swabs or on samples of formalin-fixed and paraffin wax
      embedded brain. To our knowledge, this is the first pathological description of
      naturally occurring cases of turkey MG meningoencephalitis in Europe.

PMID- 22878057
TI  - Dorsal dartos flap rotation versus suturing tunica albuginea to the pubic
      periosteum for correction of penile torsion: a prospective randomized study.
AB  - PURPOSE: To compare the results of dorsal dartos flap rotation versus suturing
      tunica albuginea to the pubic periosteum for correction of congenital penile
      torsion. PATIENTS AND METHODS: Seventeen patients with congenital penile torsion
      were evaluated and managed from 2006 to 2010. On a random basis, 9 patients
      underwent surgical repair using a dorsal dartos flap rotation technique (group
      1), and 8 patients by suturing tunica albuginea to the pubic periosteum (group
      2). All were followed up every 6 months. RESULTS: The mean age in group 1 was
      52.3 +/- 24.8 months, while in group 2 it was 53.4 +/- 33.6 months. Mean follow
      up was 22.3 +/- 10.2 and 21.5 +/- 7.2 months in group 1 and group 2 respectively.
      Torsion was corrected in 6 (66.7%) patients of group 1; 3 (33.3%) had residual
      torsion < 10 degrees . In group 2, correction was achieved in 6 (75.0%) patients
      and 2 (25.0%) had residual torsion < 10 degrees . The mean operative time was
      significantly less for group 1 than for group 2: 45.3 +/- 7.1 and 74.5 +/- 5.3
      min, respectively (P < 0.0001). CONCLUSIONS: In short-term prepubertal follow up,
      both dorsal dartos flap rotation and suturing tunica albuginea to the pubic
      periosteum are effective for correction of congenital penile torsion. The former
      technique is easier to perform as it requires much less dissection.

PMID- 22878058
TI  - The impact of posterior urethral valves on adult quality of life.
AB  - OBJECTIVE: To investigate the quality of life of men who had been treated for
      posterior urethral valves (PUV) in childhood. PATIENTS AND METHODS:
      Questionnaires were mailed to 108 patients with PUV treated at the Children's
      Hospital, University of Helsinki, and 67 (62%) of them responded. Three different
      questionnaires (15D, LSS, and RAND) were used to evaluate the quality of life.
      RESULTS: The total quality of life in PUV patients was reported as good compared
      to the general population in the RAND and LSS surveys. However, in the 15D
      analysis the PUV patients reported lower scores in sleeping, eating, and sexual
      activity. Those PUV patients who had been treated for renal insufficiency
      reported lower scores in several dimensions in all three surveys. Patients with
      urinary incontinence reported more sleeping problems and regarded themselves
      physically more disabled. CONCLUSIONS: The PUV patients with renal insufficiency
      or urinary incontinence had impaired quality of life in several dimensions.

PMID- 22878059
TI  - Rethinking current concepts and terminology in lower urinary tract dysfunction.

PMID- 22878060
TI  - Effect of perfusion temperature on glucose and electrolyte transport during
      hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin.
AB  - INTRODUCTION: Hyperthermic intraperitoneal chemoperfusion (HIPEC) with
      oxaliplatin is increasingly used in patients with carcinomatosis from colorectal
      cancer. For reasons of chemical stability, oxaliplatin can only be administered
      in a dextrose (D5%) solution, and this causes peroperative glucose and
      electrolyte shifts. Here, we examined the influence of perfusion temperature on
      glucose and electrolyte transport, metabolic shifts, and surgical morbidity.
      METHODS: Patients with carcinomatosis underwent cytoreduction and HIPEC using
      oxaliplatin (460 mg/m(2) in D5%, open abdomen) during 30 min at 39 degrees -41 
      degrees C. Intraperitoneal (IP) temperature was measured at three locations using
      thermocouple probes. The area under the temperature versus time curve (AUCt) was
      calculated using the trapezoid rule. The influence of perfusion temperature on
      surgical outcome was assessed using linear regression models and the Mann Whitney
      U test where appropriate. RESULTS: From July 2005 until March 2011, 145
      procedures were performed in 139 patients with a diagnosis of CRC (70%),
      pseudomyxoma peritonei (11%), ovarian cancer (10%), or miscellaneous peritoneal
      malignancies (9%). Postoperative mortality and major morbidity were 1.4% and 26%,
      respectively. Higher perfusion temperature was related to more pronounced changes
      in serum glucose (P = 0.058), sodium (P = 0.017), and lactate (P < 0.001). The
      median duration of nasogastric drainage was 5 days, and this was unrelated to
      perfusion temperature (P = 0.76). The GI fistula rate and reoperation rate were
      12.4% and 16.5% respectively; neither was related to perfusion temperature.
      CONCLUSIONS: In patients undergoing HIPEC with oxaliplatin, perfusion temperature
      exacerbates peroperative metabolic shifts but does not affect surgical outcome.

PMID- 22878061
TI  - Influence of age and gender on triglycerides-to-HDL-cholesterol ratio (TG/HDL
      ratio) and its association with adiposity index.
AB  - TG/HDL ratio has been proposed to be a good predictor of cardiovascular disease.
      The aim of this study was to determine whether TG/HDL ratio and its association
      with adiposity index are modified by age and gender. Subjects were younger (35-40
      years) and older (60-70 years) Japanese men and women (n=16,825) receiving health
      checkup examinations. TG/HDL ratio and its relationship with adiposity index such
      as waist-to-height ratio (WHtR) were compared between the age pair and between
      the gender pair. Log-transformed TG/HDL ratio was significantly higher in older
      women than in younger women, while log-transformed TG/HDL ratio was comparable in
      younger and older men. The odds ratio (OR) for high TG/HDL ratio in subjects with
      vs. subjects without high WHtR was significantly lower in older men and women
      than in younger men and women, respectively. The OR was significantly lower in
      younger men than in younger women [4.08 (3.63-4.58) (younger men) vs. 8.42 (5.55
      12.78) (younger women), p<0.01], whereas the OR was significantly lower in older
      women than in older men [3.36 (2.87-3.93) (older men) vs. 1.93 (1.31-2.85) (older
      women), p<0.01]. The results suggest that TG/HDL ratio is comparable in younger
      and older men but that TG/HDL ratio is higher in older women than in younger
      women and that the association between obesity and high TG/HDL ratio declines
      with age and is stronger in younger women than in younger men, while the
      association is weaker in older women than in older men.

PMID- 22878062
TI  - Validation of the Scale for the Assessment of Illness Behavior (SAIB) in a
      community sample of elderly people.
AB  - The aim of this study was to evaluate the construct validity of the SAIB in a
      community sample of elderly people. The SAIB was administered to a large
      community sample representative of the German population aged 60-85 years
      (n=1593). The original model was assessed and then refined through confirmatory
      and exploratory factor analyses. Criterion validity was evaluated by comparing
      SAIB scores with external criteria in 3 categories: subjective health, chronic
      illness and health care utilization. The originally suggested five factor
      structure of the SAIB yielded a comparative fit index (CFI) of 0.70 and the
      weighted root mean square residual (WRMR) was 3.68. A shortened questionnaire
      with 13 items and four factors resulted in better model fit (CFI 0.97 and WRMR
      1.3). Correlations between subjective health and the new scales ranged from 0.06
      to 0.33. Effect sizes (Cohens d) of mean differences in factor scores between
      those with and without healthcare system contact varied by healthcare type,
      ranging from 0.05 to 0.94; effect sizes were largest in relation to contact with
      psychotherapy and alternative medicine practitioners. We propose a shortened
      version of the SAIB with a different scale structure, which resulted in better
      model fit with our data. Neither the original nor revised SAIB appeared to
      discriminate well in terms of health care use, suggesting that the illness
      behavior as currently conceptualized may not fully explain the increased use of
      healthcare in the elderly.

PMID- 22878063
TI  - Identification of possible determinants of inpatient mortality using
      Classification and Regression Tree (CART) analysis in hospitalized oldest old
      patients.
AB  - Current demographic trends suggest that there will be increasing numbers of older
      people in the future. Relatively little information is available regarding
      factors which influence mortality in the acutely unwell oldest old. This study
      uses the CART technique on data relating to the oldest old, to identify potential
      predictors of inpatient mortality in patients over 90 years old admitted acutely
      to the hospital due to various medical emergencies in two UK centers. The sample
      included 393 patients aged 90 years and older, with 67.5% females and 32.5% males
      and a mean age of 91.1 years. We aimed to generate hypotheses in order to
      identify potential acute illness prognostic indicators of inpatient mortality in
      this age group. The factors identified in this analysis which were associated
      with inpatient mortality in this patient population were raised serum urea
      concentration (>13.95 mmol/L), low oxygen saturation levels (<94%), hyponatremia
      (<128 mmol/L), and raised white cell count (>17 * 10(9)/L). The predictability of
      using these cut off points in inpatient as well as early in-hospital death should
      be validated in future studies.

PMID- 22878064
TI  - Re: emergency gastroduodenal artery embolization by sandwich technique for
      angiographically obvious and oblivious, endotherapy failed bleeding duodenal
      ulcers. A reply.

PMID- 22878065
TI  - Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under
      glaucomatous stress.
AB  - Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role
      in the survival of retinal ganglion cells (RGCs). This study reports a novel
      finding that, SH2 domain-containing phosphatase-2 (Shp-2) binds to the TrkB
      receptor in RGCs and negatively regulates its activity under glaucomatous stress.
      This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1
      and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2
      phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in
      RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2
      phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative
      stress. Collectively, these findings implicate a molecular basis of Shp2 mediated
      TrkB deactivation leading to RGC degeneration observed in glaucoma.

PMID- 22878066
TI  - Courage and character, leaders and legends: an interview with Howard Nathan.

PMID- 22878068
TI  - Expanded criteria living donors: how far can we go?
AB  - In an effort to expand the deceased donor pool, transplant centers have accepted
      expanded criteria donors as appropriate for many of the patients in the deceased
      donor pool. Translating this into the living donor pool is more complex. One must
      consider not only the quality of the organ procured but the consequences that the
      nephrectomy might have on the living donors for the rest of their lives. This
      review examines the available data on higher risk donors and the appropriateness,
      or lack thereof, of accepting them as kidney donors.

PMID- 22878067
TI  - Living kidney donors and their family caregivers: developing an evidence-based
      educational and social support website.
AB  - CONTEXT: Although graft and patient survival rates for living kidney donation are
      improved, some healthcare providers question whether volunteer donors and their
      informal caregivers are fully informed of the donation process and the risks
      involved. Donors and their family caregivers have reported that they receive
      limited information about the predonation and donor recovery process. Offering
      web-based information and social support is one way to address this gap.
      STRATEGY: Living kidney donor candidates and their family caregivers
      participating in the Living Donor Information Network for Caregiving (LINC) have
      access to a variety of online informational resources and a social support
      discussion forum throughout their living kidney donation experience. Strategies
      in the development and implementation of an online information and social-support
      resource are presented. CONCLUSIONS: Use of the LINC website for information and
      support may assist health care providers in identifying potential barriers in the
      current donation process and provide direction for enhancing knowledge and
      confidence among donors and family caregivers.

PMID- 22878069
TI  - Pregnancy after lung transplant.
AB  - The purpose of this study was to analyze pregnancy outcomes in female lung
      transplant recipients. Data were collected from the National Transplantation
      Pregnancy Registry via questionnaires, interviews, and hospital records. Twenty
      one female lung recipients reported 30 pregnancies with 32 outcomes (1 triplet
      pregnancy). Outcomes included 18 live births, 5 therapeutic abortions, and 9
      spontaneous abortions. No stillbirths or ectopic pregnancies were reported. Mean
      (SD) interval from transplant to conception was 3.6 (3.3) years (range, 0.1-11.3
      years). Comorbid conditions during pregnancy included hypertension in 16,
      infections in 7, diabetes in 7, preeclampsia in 1, and rejection in 5 women. Ten
      of the 21 recipients received a transplant because of cystic fibrosis and
      accounted for 12 pregnancy outcomes (7 live births, 3 spontaneous abortions, and
      2 therapeutic abortions). At last recipient contact, 13 had adequate function, 2
      had reduced function, 5 recipients had died (2 with cystic fibrosis), and 1
      recipient had a nonfunctioning transplant. Mean gestational age of the newborn
      was 33.9 (SD, 5.2) weeks, and 11 were born preterm (<37 weeks). Mean birthweight
      was 2206 (SD, 936) g and 11 were low birthweight (<2500 g). Two neonatal deaths
      were associated with a triplet pregnancy; one fetus spontaneously aborted at 14
      weeks and 2 died after preterm birth at 22 weeks. At last follow-up, all 16
      surviving children were reported healthy and developing well. Successful
      pregnancy is possible after lung transplant, even among recipients with a
      diagnosis of cystic fibrosis.

PMID- 22878070
TI  - Delivery in female kidney transplant recipients with hepatitis C virus infection:
      is it safe for mother and newborn?
AB  - The aim of this report is to evaluate whether pregnancy is a risk factor for poor
      outcome of infection with hepatitis C virus or for allograft deterioration among
      kidney transplant recipients. The first case was in a 41-year-old pregnant kidney
      transplant recipient with hypercreatinemia and a history of toxic hepatitis. The
      second case was treated with interferon before transplant. Tacrolimus-based
      immunosuppressive regimens were used during the pregnancies. Hypertension
      complicated both pregnancies, and the pregnancies ended with cesarean delivery at
      preterm and term with healthy but low-weight newborns. The first patient became
      positive for hepatitis C virus RNA after pregnancy without a flare in
      transaminase level. Antibodies to hepatitis C virus were negative in the
      newborns. In conclusion, pregnancy should be promoted for kidney recipients
      infected with hepatitis C virus who have stable graft and liver function.

PMID- 22878071
TI  - Rates and correlates of health maintenance behaviors after living kidney
      donation.
AB  - CONTEXT AND OBJECTIVE: Donating a kidney may provide an opportunity for donors to
      reevaluate their health maintenance behaviors (eg, regular exercise, smoking
      cessation, medical checkups). Although the effect of donation on donors' health,
      quality of life, and financial outcomes has received growing attention, no
      studies have examined whether donation is related to changes in health
      maintenance behaviors. The study aims were to (1) describe and compare kidney
      donors' health maintenance behaviors before and after donation, and (2) determine
      the correlates of health maintenance behaviors after donation. DESIGN, SETTING,
      PARTICIPANTS AND MEASURES: We conducted a telephone-interview study with 85
      randomly selected laparoscopic kidney donors in a major US transplant center to
      assess health behaviors before and after donation, postdonation characteristics
      (eg, quality of life, postsurgical pain), and demographics. RESULTS: Sample
      demographics included a median age of 48 years; 55% were female, 82% were white,
      71% were married, and 52% were college graduates. Few health behaviors changed
      significantly from before to after donation. Only the rate of medical checkups
      increased after donation (P< .001). Logistic regression was used to examine the
      association of demographics and postdonation characteristics with postdonation
      health maintenance behaviors, after adjusting for predonation behavior. Older
      age, higher income, less postsurgical pain, and better physical functioning were
      associated with more exercise after donation. Longer time since donation was
      associated with a higher prevalence of obesity. CONCLUSIONS: These results may
      help identify donors who are at greater risk for poor health maintenance
      behaviors after donation and suggest areas of health behavior that should be the
      focus of education sessions before donation.

PMID- 22878072
TI  - Viremia after lung transplant: a cohort study on risk factors and symptoms
      associated with detection of Epstein-Barr virus.
AB  - Background-The frequency and impact of detection of Epstein-Barr virus in the
      blood of lung and heart-lung transplant recipients in the postoperative period is
      poorly characterized.Objective-To investigate the frequency of virus detection,
      associated clinical symptoms and risk factors, and influence of virus detection
      on outcome.Methods-A cohort of 98 lung transplant recipients were monitored for
      Epstein-Barr virus in blood before transplant and during their posttransplant
      hospital stay (median 4 weeks, range 1-21 weeks). Patients were followed up for
      retransplant or death for a median of 17 months.Results-Epstein-Barr virus DNA
      was detected in 15 recipients (18.1%) before and in 39 recipients (41.5%) after
      transplant. Median viral load after transplant was 2300 copies per milliliter of
      blood (range, 900-45 000 copies/mL). Detection of Epstein-Barr virus DNA before
      transplant and mechanical ventilation before transplant were associated with
      detection of Epstein-Barr virus DNA after transplant. Shortness of breath,
      fatigue, and hoarseness were associated with detection of viral DNA after
      transplant. The incidence of retransplant or death was not increased in
      recipients who had viral DNA detected in their blood.Conclusions-Epstein-Barr
      virus DNA in the blood before transplant and mechanical ventilation before
      transplant were associated with detection of viral DNA after transplant.
      Detection of viral DNA after transplant was frequent and clinically relevant.

PMID- 22878073
TI  - Increasing donor designation through black churches: results of a randomized
      trial.
AB  - CONTEXT: African Americans are disproportionately represented among those
      awaiting a transplant, but many are reluctant to donate their organs. OBJECTIVE:
      To test the effectiveness of using lay health advisors to increase organ donation
      among church members. DESIGN: Churches were pair-matched by average estimated
      income and size and then randomized to 1 of 2 interventions: one addressing organ
      donation and the other addressing increasing consumption of fruits and
      vegetables. SETTING: Twenty-two African American churches in Southeast Michigan.
      PATIENTS OR OTHER PARTICIPANTS: Church members were trained to serve as lay
      health advisors (called peer leaders). INTERVENTIONS: Peer leaders conducted
      organ donation discussions with church groups and showed a DVD created for this
      program that was tailored to African American churches. MAIN OUTCOME MEASURES:
      The primary outcome was verified registration in the state's donor registry.
      Participants also completed pre/post questionnaires regarding their attitudes
      about organ donation. RESULTS: Once clustering, baseline value, and demographics
      were adjusted for, the intervention and comparison groups did not differ on any
      of the 3 attitude scales on the posttest. In logistic regression analysis, with
      baseline donation status, demographics, and church clustering controlled for, the
      odds of self-reported enrollment at 1-year posttest did not differ by condition
      (odds ratio, 1.23; 95% CI, 0.87-1.72). A total of 211 enrollments in the state
      registry from participating churches were verified. Of these, 163 were from
      intervention churches and 48 were from comparison churches. CONCLUSIONS: Use of
      lay health advisors through black churches can increase minority enrollment in a
      donor registry even absent change in attitudes.

PMID- 22878074
TI  - Click to "like" organ donation: the use of online media to promote organ donor
      registration.
AB  - CONTEXT: Efforts to promote organ donation have traditionally relied on mass
      mediated or interpersonal communication to promote donor registration. Despite
      its popularity, the use of online media has yet to be carefully evaluated as a
      platform to promote organ donation. OBJECTIVE: To describe results of an
      intervention to promote donor registration that relies solely on online media to
      communicate to target audiences. DESIGN: For 3 years, 6 campaigns were
      implemented in 3 different online media formats. SETTING: Online media formats
      included (1) traditional online advertising, (2) student seeders' social
      networking sites campaigns, and (3) challenge campaigns. PARTICIPANTS: Online
      media campaigns primarily targeted college-aged individuals.Intervention-Each
      campaign directed individuals to the dedicated project website, where they could
      access educational material about donation and request a donor registration card.
      MAIN OUTCOME MEASURES: Unique website visitors, webpages viewed per site visit,
      time spent on site, and organ donor cards requested/received were tracked in
      relation to each online media format. RESULTS: Traditional online advertising
      offered greater message exposure but failed to result in a higher proportion of
      website visitors who registered their donation intentions. Use of student seeders
      (ie, motivated students who promote donation by using social networking sites)
      and challenge campaigns resulted in greater attention to the project website,
      donor card requests, and subsequent returns. Additional research is recommended
      to reveal the effect of combining 2 or more varying online media formats within a
      single campaign.

PMID- 22878075
TI  - Identifying risk factors in renal allografts before transplant: machine-measured
      renal resistance and posttransplant allograft survival.
AB  - Enhancement of renal allograft function and survival in an era where expanded
      criteria donors are increasingly used requires validated selection criteria. The
      goal of this retrospective study was to evaluate the significance of
      pretransplant donor and allograft parameters to identify risk factors that can be
      used in a model to predict 1-year allograft outcomes. Donor demographic factors,
      donor type, and allograft parameters such as biopsy results and machine-measured
      renal resistance were correlated with 1-year graft outcome. The Kaplan-Meier
      method was used to estimate graft survival using the categorical predictors of
      donor type, donor age, and machine measured renal resistance at 1.5, 3, and 5
      hours. The log-rank test was used to test the difference in survival curves
      between cohorts. The Cox regression analysis was used to estimate hazard ratios
      for machine-measured renal resistance, donor age, donor terminal creatinine
      level, donor's estimated glomerular filtration rate, cold ischemia time, and
      percent glomerulosclerosis. The data show that machine-measured renal resistance
      at 3 and 5 hours has a statistically significant inverse relationship to 1-year
      graft survival. All other risk factors had no correlation with 1-year graft
      survival. The machine-measured renal resistance at 3 hours is the earliest
      significant predictor of 1-year allograft outcome.

PMID- 22878076
TI  - A large-scale qualitative study of the potential use of social media by
      university students to increase awareness and support for organ donation.
AB  - OBJECTIVE: A 2-year study funded by the United States Department of Health and
      Human Services, Health Resources and Services Administration was conducted to
      identify a conceptual model of how college students, particularly those in
      student organizations, can be the social media catalyst for viral communications
      designed to motivate others to learn about the need of organ donation and become
      organ donors. This study reports the qualitative findings. DESIGN AND DATA
      COLLECTION: Methods used included an advisory committee, key informant
      interviews, and focus groups. A total of 317 individuals participated, including
      246 students, 19 student organization advisors, 27 organ transplant experts, 20
      university health care professionals, and 5 social media experts. ANALYTICAL
      METHODS: SPSS Text Smart content analysis software was used to code respondents'
      verbal comments into various categories. The analysis results in groupings of
      words that represent the main discussion topics. RESULTS: College students
      understand the need for organ donation and they want to make a difference. The
      donation community needs to overcome several barriers to motivate college
      students to become organ donors and donor advocates, including (1) lack of a
      personal connection with donation, (2) lack of (factual) knowledge about organ
      donation and how to sign up, (3) common myths and misconceptions, and (4)
      students have a short-term perspective on life. CONCLUSION AND IMPLICATIONS: Our
      findings suggest that the donation community can motivate college students to
      register as organ donors and become advocates through outreach efforts that use
      social media, student organizations, and other college-based media.

PMID- 22878077
TI  - Introduction to genetic processes in transplantation.
AB  - Recent investigations have explored how analyses of genetic DNA from organ donors
      and recipients may be helpful during organ allocation so as to reduce graft
      rejection or improve dosing of immunosuppressive medications. This discussion
      reviews those data and the processes by which genetic coding controls the
      production of protein that is important in cellular structure and function during
      donor and recipient care. Changes in gene structure (polymorphisms or mutations)
      may occur spontaneously or as a result of cell interactions with environmental
      factors, and may be associated with recognized diseases or, potentially, could
      reduce or worsen graft rejection.

PMID- 22878078
TI  - The fear associated with blood and organ donation: an explication of fright and
      anxiety.
AB  - CONTEXT: Fear inhibits potential donors' willingness to engage in behaviors.
      Theoretically, fright and anxiety are differentially associated with blood and
      organ donation, respectively. Fright is the experience of an immediate harm,
      whereas anxiety is a fear of the unknown. OBJECTIVE: To compare the fear-related
      concepts of fright and anxiety in relation to blood donation and signing an organ
      donor card. DESIGN: Scales were created to separate the 2 fear types that were
      consistent in theme and addressed the same dependent variables fright and
      anxiety. SETTING AND PARTICIPANTS: Participants were 509 college students at a
      large midwestern university. RESULTS: Survey responses from 509 participants
      supported the theoretical explication of the 2 fear types. Multisample analyses
      and multimeasurement models using confirmatory factor analysis supported that
      fright and anxiety were differentially associated with the contexts of blood and
      organ donation. CONCLUSIONS: The results supported the theoretical proposal that
      fright and anxiety are differentially related. The ability to measure such
      emotions will help future researchers create models that are more accurate for
      predicting potential donors and create messages to assuage fears. A greater
      understanding of fear will lead to more effective messages.

PMID- 22878079
TI  - "Every organ, every time" attitude teamed up with SoftMD results in successful
      lung transplant from a 72-year-old donor.
AB  - Since 1998, lung transplants have increased almost 75%, making lung transplant
      the fastest growing form of organ transplant in the United States. However, the
      supply of transplantable lungs continues to fall short of the demand. Strategies
      for expanding the lung donor pool by increasing the number of older donor lungs
      used has been effective, although these donors do not meet typical clinical
      selection criteria based on age. In these older donors, effective communication
      of in-depth donor information is necessary to place and transplant lungs
      successfully. The following case study illustrates how an "every organ, every
      time" attitude combined with a technique to communicate clinical information
      resulted in the successful transplant of 72-year-old donor lungs into a bilateral
      lung recipient. Since the case outlined in this study, the organ procurement
      organization has successfully recovered and transplanted an additional 2 lungs
      from a 74-year-old and 1 lung from a 76-year-old, 2 of the oldest lung donors in
      the United States. This case demonstrates that although many older donor lungs
      are deemed unsuitable by clinical selection criteria, an extended criteria
      population offers an untapped resource for donor organs.

PMID- 22878080
TI  - Overcoming alterations in body image imposed by the left ventricular assist
      device: a case report.
AB  - Little is known about clothing issues among patients with implantable left
      ventricular assist devices (LVADs). This article describes the experience of a
      woman who had challenges in adapting to an altered body image imposed by the
      external components of the LVAD system. The woman discusses her problems about
      clothes that fit her personal style and shares her strategies and recommendations
      in overcoming the problem. Her description of how she approached and resolved the
      problem is situated within the Apparel Body Construct Model. In this context,
      appropriate selection of apparrel is crucial not only to preserving the integrity
      and function of the LVAD system but also to the recipient's satisfaction with her
      body image. The information presented is a catalyst for knowledge development and
      heightening health care providers' awareness of patients' perception of body
      image, which is vital to adapting to an LVAD as a component of the recipient's
      body and life.

PMID- 22878081
TI  - Development of a microcantilever-based immunosensing method for mycotoxin
      detection.
AB  - Mycotoxins, such as aflatoxins and ochratoxin A, are presently considered as the
      most important chronic dietary risk factor, more than food additives or pesticide
      residues. Therefore, the serious health and economic consequences of mycotoxin
      contamination have created the need for rapid, sensitive, and reliable techniques
      to detect such dangerous molecules within foodstuffs. We here report on the
      development of an innovative immunosensing method for mycotoxin detection, based
      on antibody-immobilized microcantilever resonators, a promising label free
      biosensing technique. A considerable part of the work is devoted to show the
      effect on microcantilever resonance frequency of the composition of the
      incubation buffer, as well as of the washing and drying procedure. We show the
      feasibility of using microcantilever resonator arrays to effectively identify
      total aflatoxins and ochratoxin A, at low concentrations (3 ng/mL and less than 6
      ng/mL, respectively), with relatively low uncertainty (about 10%) and good
      reproducibility for the same target concentration. Furthermore, the developed
      immunosensing method shows a limited cross-reactivity to different mycotoxins,
      paving the way to a highly specific technique, able to identify different
      mycotoxins in the sample. To our knowledge, this work represents the first
      example in literature of successfully immunodetection of low concentrations of
      multiple mycotoxins by microcantilever resonator arrays.

PMID- 22878082
TI  - Disposable sensor based on enzyme-free Ni nanowire array electrode to detect
      glutamate.
AB  - Enzyme free electrochemical sensor platform based on a vertically aligned nickel
      nanowire array (NiNAE) and Pt coated nickel nanowire array (Pt/NiNAE) have been
      developed to detect glutamate. Morphological characterisation of Ni electrodes
      was carried out using scanning and transmission electron microscopy combined with
      energy dispersive X-ray (SEM-EDX), X-ray diffraction (XRD) and transmission
      electron microscopy (TEM). Cyclic voltammetry (CV) and amperometry were used to
      evaluate the catalytic activity of the NiNAE and the Pt/NiNAE for glutamate. It
      has been found that both NiNAE and Pt/NiNAE electrodes showed remarkably enhanced
      electrocatalytic activity towards glutamate compared to planar Ni electrodes, and
      showed higher catalytic activity when compared to other metallic nanostructure
      electrodes such as gold nanowire array electrodes (AuNAE) and Pt coated gold
      nanowire array electrode (Pt/AuNAE). The sensitivity of NiNAE and Pt/NiNAE has
      been found to be 65 and 96 MUA mM(-1) cm(-2), respectively, which is
      approximately 6 to 9 times higher than the state of the art glutamate sensor.
      Under optimal detection conditions, the as prepared sensors exhibited linear
      behaviour for glutamate detection in the concentration up to 8mM for both NiNAE
      and Pt/NiNAE with a limit of detection of 68 and 83 MUM, respectively.
      Experimental results show that the vertically aligned ordered nickel nanowire
      array electrode (NiNAE) has significant promise for fabricating cost effective,
      enzyme-less, sensitive, stable and selective sensor platform.

PMID- 22878083
TI  - The effect of uniform capture molecule orientation on biosensor sensitivity:
      dependence on analyte properties.
AB  - Uniform orientation of capture molecules on biosensors has been reported to
      increase sensitivity. Here it is investigated which analyte properties contribute
      to sensitivity by orientation. Orientation of capture molecules on biosensors was
      investigated using variable domains of llama heavy-chain antibodies (VHHs) as
      capture molecule, and a surface plasmon resonance (SPR) chip as biosensor. Two
      VHHs were tested in this study: one recognizing foot-and-mouth disease virus
      (FMDV) and another recognizing the 16 kDa heat-shock protein of Mycobacterium
      tuberculosis. SPR chips with randomly immobilized biotinylated VHHs were compared
      to streptavidin-coated SPR chips, on which similar quantities of oriented
      biotinylated VHHs were non-covalently immobilized. Analytes that differ in
      molecular weight, epitope number and epitope affinity were compared using the
      FMDV-recognizing VHH. When binding of intact FMDV particles (146 S; 8200 kDa) or
      pentameric FMDV coat protein aggregates (12 S; 282 kDa) was detected, a modest (1
      2-fold) increase in sensitivity was observed. When a 26-residue peptide (3 kDa)
      containing the epitope for VHH recognition was tested, much larger effects of
      capture molecule orientation (14-fold) on signal were observed. A 20-227-fold
      improvement was also observed when the epitope peptide was covalently linked to
      bovine serum albumin (67 kDa) or R-phycoerythrin (240 kDa). The results indicate
      that orientation of the capture molecule hardly affects high-affinity
      interactions, while it leads to strong improvements in sensitivity for lower
      affinity interactions.

PMID- 22878085
TI  - Colorful success: preschoolers' use of perceptual color cues to solve a spatial
      reasoning problem.
AB  - Spatial reasoning, a crucial skill for everyday actions, develops gradually
      during the first several years of childhood. Previous studies have shown that
      perceptual information and problem solving strategies are critical for successful
      spatial reasoning in young children. Here, we sought to link these two factors by
      examining children's use of perceptual color cues and whether their use of such
      cues would lead to the acquisition of a general problem solving strategy. Forty
      eight 3-year-olds were asked to predict the trajectory of a ball dropped into one
      of three intertwined tubes. Children who received additional perceptual cues in
      the form of distinctly colored tubes succeeded twice as often as those who did
      not receive the cues. A third group of children who received the additional cues
      on only the first half of the test trials succeeded while the cues were present
      but reverted to making errors once they were removed. These findings demonstrate
      that perceptual color cues provide preschoolers with answers to spatial reasoning
      problems but might not teach children a general strategy for solving the problem.

PMID- 22878084
TI  - Cointegrate-resolution of toluene-catabolic transposon Tn4651: determination of
      crossover site and the segment required for full resolution activity.
AB  - Tn3-family transposon Tn4651 from Pseudomonas putida mt-2 plasmid pWW0 carries
      two divergently transcribed genes, tnpS and tnpT, for cointegrate-resolution.
      While tnpS encodes a tyrosine recombinase, tnpT encodes a protein that shows no
      homology to any other characterized protein. The Tn4651 resolution site was
      previously mapped within the 203-bp fragment that covered the tnpS and tnpT
      promoter region. To better understand the molecular mechanisms underlying the
      Tn4651 cointegrate-resolution, we determined the extent of the functional
      resolution site (designated the rst site) of Tn4651 and the location of the
      crossover site for the cointegrate-resolution. Deletion analysis of the rst
      region localized the fully functional rst site to a 136-bp segment. The analysis
      of the site-specific recombination between Tn4651 rst and a rst variant from the
      Tn4651-related transposon, Tn4661, indicated that the crossover occurs in the 33
      bp inverted repeat region, which separates the 136-bp functional rst site into
      the tnpS- and tnpT-proximal segments. Electrophoretic mobility shift assays
      demonstrated specific binding of TnpT to the 20-bp inverted repeat region in the
      tnpT-proximal segment. The requirement for accessory sequences on both sides of
      the crossover site and the involvement of the unique DNA-binding protein TnpT
      suggest that the Tn4651-specified resolution system uses a different mechanism
      than other known resolution systems. Furthermore, comparative sequence analysis
      for Tn4651-related transposons revealed the occurrence of DNA exchange at the rst
      site among different transposons, suggesting an additional role of the TnpS-TnpT
      rst system in the evolution of Tn4651-related transposons.

PMID- 22878086
TI  - Wide eyes and drooping arms: adult-like congruency effects emerge early in the
      development of sensitivity to emotional faces and body postures.
AB  - Adults' and 8-year-old children's perception of emotional faces is disrupted when
      faces are presented in the context of incongruent body postures (e.g., when a sad
      face is displayed on a fearful body) if the two emotions are highly similar
      (e.g., sad/fear) but not if they are highly dissimilar (e.g., sad/happy). The
      current research investigated the emergence of this adult-like pattern. Using a
      sorting task, we identified the youngest age at which children could accurately
      sort isolated facial expressions and body postures and then measured whether
      their accuracy was impaired in the incongruent condition. Among the child
      participants, 6-year-olds showed congruency effects for sad/fear, but even 4-year
      olds did not do so for sad/happy. Early emergence of this adult-like pattern is
      consistent with the dimensional and emotional seed models of emotion perception,
      although future research is needed to test the relative validity of these two
      models. Testing children with emotional faces presented in the context of body
      postures and background scenes is an important step toward understanding how they
      perceive emotions on a daily basis.

PMID- 22878087
TI  - A rod domain sequence in segment 1B triggers dimerisation of the two small
      Branchiostoma IF proteins B2 and A3.
AB  - Previously, we cloned two Branchiostoma IF proteins A3 and B2 and demonstrated
      that both can form heteropolymeric IF based on a coiled coil dimer consisting of
      one B2 and one A3 polypeptide. In this study we continued in the characterisation
      of the B2/A3 heterodimer by searching for the sequences that play an important
      role in the triggering of the B2/A3 heterodimer. Using a series of deletion and
      chimeric B2, A3 and B1 constructs and the overlay assay as a tool, we were able
      to identify a part of the B2 sequence (segment 1A, linker L1 and the N-terminal
      part of segment 1B) which retains the ability of the full length protein B2 to
      specifically recognize A3 in blot overlays. Moreover, inspection of this A3
      competent B2 fragment identified a short sequence in segment 1B which shares with
      the currently known trigger-like motif of cortexillin and other coiled coil
      proteins potential to form multiple inter-chain ionic interactions. Thus, a
      common and essential feature of trigger sequences with different primary
      structures found so far in IF and other coiled coil proteins seems to be their
      ability to form multiple inter-chain ionic interactions which brings the chains
      close to one another and allows coiled coil formation to propagate accordingly.

PMID- 22878088
TI  - Income and heart disease mortality trends in Sao Paulo, Brazil, 1996 to 2010.
AB  - BACKGROUND: Reductions in heart disease mortality rates are variable according to
      socioeconomic status. METHODS: We performed a time trend analysis of all heart
      diseases (all circulatory diseases, except rheumatic, cerebrovascular, and aortic
      diseases) comparing three different household income levels (high, middle, and
      low) in the city of Sao Paulo from 1996 to 2010. RESULTS: A total of 197,770
      deaths were attributed to heart diseases; 62% of them were due to coronary
      diseases. The rate of death due to heart diseases declined for the city as a
      whole. The annual percent change (APC) and 95% confidence intervals for men
      living in the high, middle and low income areas were -4.1 (-4.5 to -3.8), -3.0 (
      3.5 to -2.6), and -2.5 (-2.8 to -2.1), respectively. The decline in death rate
      was greatest among men in the wealthiest area. The trend rates of women living in
      the high-income area had one joinpoint; APC was -4.4 (-4.8 to -3.9) from 1996
      2005 and -2.6 (-3.8 to -1.4) from 2005-2010. Middle and low income areas had an
      APC of -3.6 (-4.1 to -3.1) and -3.0 (-3.2 to -2.7) from 1996-2010, respectively.
      During the last 5years of observation, there was a gradient of the decline of the
      risk of death, faster for people living in the wealthiest area and slower for
      people living in the more deprived neighborhoods. CONCLUSION: Reduction in deaths
      due to heart diseases is greatest for men and women living in the wealthiest
      neighborhoods.

PMID- 22878089
TI  - Cardiac quadruple-fusion imaging: a brief report on a novel integrated
      multimodality approach for in vivo visualization of transplanted stem cells.

PMID- 22878090
TI  - Peutz-Jeghers syndrome-associated atypical mucinous proliferation of the uterine
      cervix: a case of minimal deviation adenocarcinoma ('adenoma malignum') in situ.
AB  - We describe a case of a non-invasive precursor of minimal deviation
      adenocarcinoma (MDA) of the uterine cervix, associated with Peutz-Jeghers
      syndrome (PJS). A 27-year-old woman, who had been followed for PJS, was referred
      to the gynecology clinic. Colposcopic examination demonstrated a small polypoid
      lesion in the transformation zone. Microscopic examination of the biopsy specimen
      demonstrated papillary proliferation of the mucinous epithelium with bland
      nuclear morphology. Conization revealed lobular endocervical glandular
      hyperplasia (LEGH) with distinct nuclear anaplasia, as well as papillary
      proliferation of the mucinous epithelium with mild to moderate nuclear
      abnormalities. This case suggests that the incipient phase of PJS-associated MDA
      is related to atypical LEGH ("MDA in situ"), and indicates the importance of
      early screening and surveillance by gynecologists in cases of PJS to detect
      cervical adenocarcinomas.

PMID- 22878091
TI  - A SEM study of antennal and maxillary sensilla in Zema gressitti Fennah
      (Hemiptera: Fulgoromorpha: Tropiduchidae).
AB  - The sensory organs on the antennae and maxillary plates of Zema gressitti Fennah
      (Hemiptera: Fulgoromorpha: Tropiduchidae) are studied using scanning electron
      microscopy. Four types of antennal sensilla are reported: trichoid sensilla on
      the antennal scape and antennal pedicel, plate organs on the antennal pedicel,
      campaniform sensilla on the antennal scape and antennal pedicel, and coeloconic
      sensilla in Bourgoin's organ on the antennal flagellum. Cuticular denticles and
      cuticular microtubercles are also present on the antennal pedicel. On the
      maxillary plates, three campaniform sensilla are discovered. Additionally, Evans'
      organs are described as placoid sensilla sunk into deep cuticular cavities on the
      maxillae below the antennae. The morphology of the sensory equipments in this
      species is provided for possible use in taxonomic and phylogenetic studies within
      the Tropiduchidae and Fulgoromorpha.

PMID- 22878092
TI  - Left atrium reverse remodeling in patients with mitral valve stenosis after
      percutaneous valvuloplasty: a 2- and 3-dimensional echocardiographic study.
AB  - INTRODUCTION AND OBJECTIVES: The left atrium is clinically relevant in patients
      with mitral valve stenosis. The objective of this study was to analyze the
      effects of percutaneous balloon valvuloplasty on left atrium volumes and the left
      atrium emptying fraction in symptomatic mitral valve stenosis patients using 2
      dimensional and real-time 3 -dimensional transthoracic echocardiography. METHODS:
      We carried out a prospective study of 28 consecutive symptomatic mitral valve
      stenosis patients, aged 22-72 (39 [11.5]) years, 24/28 (85.6%) women, who
      underwent to percutaneous balloon valvuloplasty between March 2009 and May 2011.
      Patients underwent 2- and 3-dimensional transthoracic and transesophageal
      echocardiography (atrial fibrillation) and invasive mitral valve area
      measurement. Echocardiographic analysis was performed before, 72 h after and 12
      months after percutaneous balloon valvuloplasty. The following parameters were
      analyzed: a) mitral valve area (2-dimensional planimetry, pressure half-time, 3
      dimensional echocardiography, invasive hemodynamic measurement); b) indexed left
      atrium maximum and indexed minimum volumes, and c) left atrium emptying fraction.
      RESULTS: The 3-dimensional parameters of the mitral valve stenosis patients
      before and 72 h and 12 months after percutaneous balloon valvuloplasty were as
      follows: a) mitral valve area: 0.9 (0.1) cm(2); 1.8 (0.2) cm(2) (P<.001); 1.7
      (0.2) cm(2) (P<.001); b) left atrium maximum volumes: 49.9 (12) mL/m(2); 42
      (11.4) mL/m(2) (P<.001); 40.3 (10.2) mL/m(2) (P<.001), and c) left atrium
      emptying fraction: 30.1 (9.4%); 40.6 (7.4%) (P<.001); 44.1 (8%) (P<.001),
      respectively. CONCLUSIONS: In symptomatic mitral valve stenosis patients who
      underwent percutaneous balloon valvuloplasty analysis by 2- and 3-dimensional
      echocardiography, improvements in left atrium reverse remodeling and left atrium
      emptying fraction were observed 72 h and 12 months after the procedure.

PMID- 22878093
TI  - Bovine lameness: still more to learn.

PMID- 22878094
TI  - The dynamics of digital dermatitis in populations of dairy cattle: model-based
      estimates of transition rates and implications for control.
AB  - Five groups of dairy cows affected by digital dermatitis were subjected to five
      different footbath strategies and evaluated at regular 3-weekly intervals. A
      standard protocol was used to record five different stages of disease from early
      (M1), acute ulcerative (M2), healing (M3) and chronic lesions (M4) in addition to
      the negative stage of disease (M0). The effect of the footbathing was evaluated
      using mathematical modelling for the transmission dynamics of infections and
      summarized using the reproduction ratio R(0). Sensitivity analysis for a range of
      parameters in the mathematical model showed that the speed of detecting acute
      lesions and the efficiency with which those lesions were treated were the key
      parameters which determined whether lesions became more severe or whether they
      healed.

PMID- 22878096
TI  - A retrospective study of the orthopoxvirus molecular evolution.
AB  - The data on the structure of conserved genes of the Old and New World
      orthopoxviruses and unclassified Yoka poxvirus were used for a Bayesian dating of
      their independent evolution. This reconstruction estimates the time when an
      orthopoxvirus ancestor was transferred to the North American continent as
      approximately 50 thousand years ago (TYA) and allows for relation of this time
      interval with the global climate changes (with one of the short-term warmings
      during the Last Ice Age). The onset of the Yoka poxvirus evolution was assessed
      as approximately 90TYA. Availability of a large number of genome sequences of
      various cowpox virus strains provided for a comprehensive analysis of the
      orthopoxvirus evolutionary history. Such a study is especially topical in view of
      the postulated role of this virus in the evolution of various orthopoxviruses,
      namely, as an progenitor virus. The computations have demonstrated that the
      orthopoxviruses diverged from the ancestor virus to form the extant species about
      10TYA, while the forbear of horsepox virus separated about 3TYA. An independent
      evolution of taterapox, camelpox, and variola viruses commenced approximately
      3.5TYA. Study of the geographic distribution areas of the hosts of these three
      orthopoxviruses suggests the hypothesis on the region of their origin. It is
      likely that these viruses first emerged in Africa, in the region of the Horn of
      Africa, and that the introduction of camels to East Africa induced their
      divergent evolution.

PMID- 22878095
TI  - Hepatitis C virus entry: role of host and viral factors.
AB  - Hepatitis C virus (HCV) has been considered to be a significant risk factor in
      developing liver associated diseases including hepatocellular carcinoma all over
      the world. HCV is an enveloped positive strand virus comprising a complex between
      genomic RNA and viral envelope glycoproteins (E1 and E2), which are anchored
      within host derived double-layered lipid membrane surrounding the nucleocapsid
      composed of several copies of core protein. HCV cell entry is the first step in
      infection and viral replication into host cells mainly hepatocytes. HCV cell
      entry is a complex process involving both the viral (envelope glycoproteins
      E1/E2) and host factors (cellular receptors and associated factors i.e. CD81, SR
      BI, LDL-R, CLDN1, Occludin, DC-SIGN, L-SIGN and Glycosaminoglycans). Besides
      these the expression of certain other conditions such as polarization and EWI-2
      expression inhibits the viral cell entry. Exploring the mechanism of HCV entry
      will help to better understand the viral life cycle and possible therapeutic
      targets against HCV infection including viral and host factors involved in this
      process. New strategies such as RNAi represents a new option for targeting the
      host or viral factors for prevention and therapeutic against HCV infection. In
      the current review we try to summarize the current knowledge about mechanism and
      interaction of cellular and viral factors involved in HCV cell entry and its
      implication as therapeutic target to inhibit HCV infection.

PMID- 22878097
TI  - Palliative care for patients with gastrointestinal cancer dying under surgical
      care: a case for acute palliative care units?
AB  - BACKGROUND AND AIMS: Patients with advanced gastrointestinal cancer may present
      late to hospital services and die under surgical care. The aim of this study was
      to examine end of life care in patients dying of gastrointestinal cancer in
      Scottish hospital surgical wards. METHODS: The Scottish Audit of Surgical
      Mortality prospectively peer reviews all inpatient deaths under the care of a
      consultant surgeon. Patients who died with gastrointestinal cancer under surgical
      care from 1994 to 2006 were evaluated for operative interventions, adverse
      events, and palliative care provision. Data was compared with inpatient data from
      the Information Statistics Division of NHS Scotland. RESULTS: A total of 8019
      patients died with gastrointestinal cancer on a surgical ward over 12 years. For
      4350 (54%), no operation or endoscopy was performed during the final admission
      and adverse events were identified in only 86 (2%) of these patients, most
      commonly due to a complication of an interventional procedures. Specialist
      palliative care was provided to 57% of patients and was not influenced by cancer
      site. CONCLUSION: A substantial proportion of patients die with gastrointestinal
      cancer on general surgical wards without operative or endoscopic intervention and
      may receive better end of life care in an acute palliative care setting.

PMID- 22878098
TI  - An analysis of microvessel density in salivary gland tumours: a single centre
      study.
AB  - BACKGROUNDS: Microvessel density (MVD) can be used for determining neoplastic
      neovascularisation. Tumour angiogenesis correlates with prognosis of cancers in
      many organs. The aims of this study were to evaluate MVD as demonstrated by CD31
      and CD105 in salivary gland tumours (SGTs), and to correlate the MVD results with
      clinicopathological characteristics of the tumours. MATERIALS AND METHODS: Using
      a retrospective cohort study design, we enrolled SGTs patients at the Faculty of
      Dentistry, Chulalongkorn University, Bangkok, Thailand, over the 22-year period.
      The predictor variables included demographic, anatomic and histopathological
      parameters. The outcome measure was average CD31-MVD and CD105-MVD counted by the
      "hot spot" method. Descriptive, uni- and bivariate statistics were computed, and
      P <0.05 was considered statistically significant. RESULTS: The study sample
      consisted of 43 subjects with a mean age of 39.6 +/- 17.8 years (range, 9-82),
      including 26 females (60.5%), diagnosed with SGTs. In this cohort, 58.1% of the
      cases were benign, and 83.7% were minor SGTs. There was a significant correlation
      between CD31-MVD and CD105-MVD (r = 0.8, P < 0.001), but mean CD31-MVD and CD105
      MVD were 17.7 +/- 9.3 and 12.8 +/- 7.4, respectively (P = 0.009). Age, gender and
      tumour site were not individually associated with significant differences between
      CD31-MVD and CD105-MVD. Tumours with myoepithelial cells had lower MVD than those
      without myoepithelial cells (P = 0.04 for CD31; P = 0.03 for CD105). Only CD105
      MVD showed statistical difference between benign and malignant SGTs (P = 0.01).
      CONCLUSIONS: These results suggest that MVD in SGTs can be demonstrated by CD31
      and CD105. Despite a strong correlation, CD31-MVD is always higher than CD105-MVD
      and cannot differentiate between benign and malignant SGTs. The presence of
      myoepithelial cells within SGTs affects the MVD analysis using either CD31 or
      CD105, while age, gender and tumour location do not.

PMID- 22878099
TI  - High expression of ADAM8 correlates with poor prognosis in hepatocellular
      carcinoma.
AB  - OBJECTIVES: To evaluate the association between ADAM8 tissue expression and
      patient prognosis in hepatocellular carcinoma (HCC). METHODS: ADAM8 expression
      was analyzed using immunohistochemical staining methods on tissue samples from a
      consecutive series of 105 HCC patients who underwent resections between 2000 and
      2006. The correlation of ADAM8 expression and patients' clinicopathological
      parameters was evaluated. Survival analysis was performed using the Kaplan-Meier
      method and Cox's proportional hazards model. RESULTS: ADAM8 was highly expressed
      in 54.3% of the HCC patients. The ADAM8 expression level was closely associated
      with serum AFP elevation, tumor size, histological differentiation, tumor
      recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis
      showed that a high expression level of ADAM8 resulted in a significantly poor
      prognosis of HCC patients. Multivariate analysis revealed that ADAM8 expression
      level was an independent prognostic parameter for the overall survival rate of
      HCC patients. CONCLUSIONS: These findings provide evidence that a high expression
      level of ADAM8 serves as a biomarker for poor prognosis for HCC. Thus, we
      speculate that ADAM8 may be a potential target of antiangiogenic therapy for HCC.

PMID- 22878100
TI  - Degradation of terbuthylazine, difenoconazole and pendimethalin pesticides by
      selected fungi cultures.
AB  - Contamination of waters by xenobiotic compounds such as pesticides presents a
      serious environmental problem with substantial levels of pesticides now
      contaminating European water resources. The aim of this work was to evaluate the
      ability of the fungi Fusarium oxysporum, Aspergillus oryzae, Lentinula edodes,
      Penicillium brevicompactum and Lecanicillium saksenae, for the biodegradation of
      the pesticides terbuthylazine, difenoconazole and pendimethalin in batch liquid
      cultures. These pesticides are common soil and water contaminants and
      terbuthylazine is considered the most persistent triazine herbicide in surface
      environments. P. brevicompactum and L. saksenae were achieved by enrichment,
      isolation and screening of fungi capable to metabolize the pesticides studied.
      The isolates were obtained from two pesticide-primed materials (soil and
      biomixture). Despite the relatively high persistence of terbuthylazine, the
      results obtained in this work showed that the fungi species studied have a high
      capability of biotransformation of this xenobiotic, comparatively the results
      obtained in other similar studies. The highest removal percentage of
      terbuthylazine from liquid medium was achieved with A. oryzae (~80%), although
      the major biodegradation has been reached with P. brevicompactum. The higher
      ability of P. brevicompactum to metabolize terbuthylazine was presumably acquired
      through chronic exposure to contamination with the herbicide. L. saksenae could
      remove 99.5% of the available pendimethalin in batch liquid cultures. L. edodes
      proved to be a fungus with a high potential for biodegradation of pesticides,
      especially difenoconazole and pendimethalin. Furthermore, the metabolite desethyl
      terbuthylazine was detected in L. edodes liquid culture medium, indicating
      terbuthylazine biodegradation by this fungus. The fungi strains investigated
      could prove to be valuable as active pesticide-degrading microorganisms,
      increasing the efficiency of biopurification systems containing wastewaters
      contaminated with the xenobiotics studied or compounds with similar intrinsic
      characteristics.

PMID- 22878101
TI  - The effects of beach nourishment on benthic invertebrates in eastern Australia:
      impacts and variable recovery.
AB  - Beach erosion is likely to accelerate, driven by predicted consequences of
      climate change and coastal development. Erosion is increasingly combated by beach
      nourishment, adding sand to eroding shores. Because a range of engineering
      techniques exists to nourish beaches, and because these techniques differ in
      their environmental effects, assessments of ecological impacts need to be
      tailored and specific. Here we report on impacts and recovery of benthic
      invertebrates impacted by beach nourishment operations undertaken at Palm Beach
      (SE Queensland, Australia). Assessments are made based on a beyond-BACI design,
      where samples were taken once before nourishment and twice afterwards at the
      impact and two control sites. Because almost all of the sand was deposited on the
      upper beach and later moved with bulldozers down-shore, we specifically examined
      whether the effects of nourishment varied at different heights of the beach-a
      little-studied question which has management implications. Impacts on the fauna
      were massive on the upper and middle levels of the beach: samples collected two
      days after the conclusion of nourishment were entirely devoid of all invertebrate
      life ('azoic'), whereas weaker effects of nourishment were detectable on the
      lower shore. Recovery after five months also varied between shore levels. The
      sediment of the upper level near the dunes remained azoic, the fauna of the
      middle shore had recovered partially, and the lower level had recovered in most
      respects. These findings indicate that the height and position of sand placement
      are important. For example, rather than depositing fill sand on the intertidal
      beach, it could be placed in the shallow subtidal zone, followed by slow up-shore
      accretion driven by hydrodynamic forces. Alternatively, techniques that spread
      the fill sand in thin layers (to minimize mortality by burial) and leave unfilled
      intertidal refuge islands (to provide colonists) may minimize the ecological
      impacts of beach nourishment.

PMID- 22878102
TI  - Source apportionment of ambient PM2.5 in Santiago, Chile: 1999 and 2004 results.
AB  - A receptor model analysis has been applied to ambient PM(2.5) measurements taken
      at Santiago, Chile (33.5 degrees S, 70.7 degrees W) in 2004 (117 samples) and in
      1999 (95 samples) on a receptor site on the eastern side of the city. For both
      campaigns, six sources have been identified at Santiago and their contributions
      in 1999/2004 are: motor vehicles: 28 +/- 2.5/31.2 +/- 3.4%, wood burning: 24.8 +/
      2.3/28.9 +/- 3.3%, sulfates: 18.8 +/- 1.7/16.2 +/- 2.5%, marine aerosol: 13 +/-
      2.1/9.9 +/- 1.5%, copper smelters: 11.5 +/- 1.4/9.7 +/- 3.3% and soil dust: 3.9
      +/- 1.5/4.0 +/- 2.4%. Hence relative contributions are statistically the same but
      the absolute contributions have been reduced because ambient PM(2.5) has
      decreased from 34.2 to 25.1 MUg/m(3) between 1999 and 2004 at Santiago.
      Similarity of results for both data sets - analyzed with different techniques at
      different laboratory facilities - shows that the analysis performed here is
      robust. Source identification was carried out by inspection of key species in
      source profiles, seasonality of source contributions, comparison with published
      source profiles and by looking at wind trajectories computed using the Hybrid
      Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) from USA's National
      Oceanic and Atmospheric Administration (NOAA); for the wood burning sources the
      MODIS burned area daily product was used to confirm wildfire events along the
      year. Using this combined methodology we have shown conclusively that: a) marine
      air masses do reach Santiago's basin in significant amounts but combined with
      anthropogenic sources; b) all copper smelters surrounding Santiago - and perhaps
      coal-fired power plants as well - contribute to ambient PM(2.5); c) wood burning
      is the second largest source, coming from residential wood burning in fall and
      winter and from regional wildfires in spring and summer. The results of the
      present analysis can be used to improve emission inventories, air quality
      forecasting systems and cost-benefit analyses at local and regional scales.

PMID- 22878104
TI  - Functional diversity of actin cytoskeleton in neurons and its regulation by
      tropomyosin.
AB  - Neurons comprise functionally, molecularly, and spatially distinct subcellular
      compartments which include the soma, dendrites, axon, branches, dendritic spines,
      and growth cones. In this chapter, we detail the remarkable ability of the
      neuronal cytoskeleton to exquisitely regulate all these cytoplasmic distinct
      partitions, with particular emphasis on the microfilament system and its plethora
      of associated proteins. Importance will be given to the family of actin
      associated proteins, tropomyosin, in defining distinct actin filament
      populations. The ability of tropomyosin isoforms to regulate the access of actin
      binding proteins to the filaments is believed to define the structural diversity
      and dynamics of actin filaments and ultimately be responsible for the functional
      outcome of these filaments.

PMID- 22878103
TI  - Cytoskeleton assembly in Toxoplasma gondii cell division.
AB  - Cell division across members of the protozoan parasite phylum Apicomplexa
      displays a surprising diversity between different species as well as between
      different life stages of the same parasite. In most cases, infection of a host
      cell by a single parasite results in the formation of a polyploid cell from which
      individual daughters bud in a process dependent on a final round of mitosis.
      Unlike other apicomplexans, Toxoplasma gondii divides by a binary process
      consisting of internal budding that results in only two daughter cells per round
      of division. Since T. gondii is experimentally accessible and displays the
      simplest division mode, it has manifested itself as a model for apicomplexan
      daughter formation. Here, we review newly emerging insights in the prominent role
      that assembly of the cortical cytoskeletal scaffold plays in the process of
      daughter parasite formation.

PMID- 22878105
TI  - Osteohematopoietic stem cell niches in bone marrow.
AB  - In adult mammals, maturation of blood and bone cells from their respective
      progenitors occurs in the bone marrow. The marrow region contains many progenitor
      and stem cell types that are confined by their biochemical and cellular
      microenvironments, referred to as stem cell niches. The unique properties of each
      niche assist the survival, proliferation, migration, and differentiation of that
      particular stem or progenitor cell type. Among the different niches of the bone
      marrow, our understanding of the osteohematopoietic niche is the most complete.
      Its properties, described in this chapter, are a model for studying adult stem
      cell differentiation, but a lot remains unknown. Our improved understanding of
      hematopoietic stem cell biology and its relationship with the properties of these
      niches are critical in the effective and safe use of these cells in regenerative
      medicine. Here, we review the current knowledge on the properties of these niches
      and suggest how the potential of hematopoietic progenitors can be utilized in
      regenerative medicine.

PMID- 22878107
TI  - Genetics of meiosis and recombination in mice.
AB  - Meiosis is one of the most critical developmental processes in sexually
      reproducing organisms. One round of DNA replication followed by two rounds of
      cell divisions results in generation of haploid gametes (sperm and eggs in
      mammals). Meiotic failure typically leads to infertility in mammals. In the
      process of meiotic recombination, maternal and paternal genomes are shuffled,
      creating new allelic combinations and thus genetic variety. However, in order to
      achieve this, meiotic cells must self-inflict DNA damage in the form of
      programmed double-strand breaks (DSBs). Complex processes evolved to ensure
      proper DSB repair, and to do so in a way that favors interhomolog reciprocal
      recombination and crossovers. The hallmark of meiosis, a structurally conserved
      proteinaceous structure called the synaptonemal complex, is found only in meiotic
      cells. Conversely, meiotic homologous recombination is an adaptation of the
      mitotic DNA repair process but involving specialized proteins. In this chapter,
      we summarize current developments in mammalian meiosis enabled by genetically
      modified mice.

PMID- 22878106
TI  - Mechanisms for countering oxidative stress and damage in retinal pigment
      epithelium.
AB  - Clinical and experimental evidence supports that chronic oxidative stress is a
      primary contributing factor to numerous retinal degenerative diseases, such as
      age-related macular degeneration (AMD). Eyes obtained postmortem from AMD
      patients have extensive free radical damage to the proteins, lipids, DNA, and
      mitochondria of their retinal pigment epithelial (RPE) cells. In addition,
      several mouse models of chronic oxidative stress develop many of the pathological
      hallmarks of AMD. However, the extent to which oxidative stress is an etiologic
      component versus its involvement in disease progression remains a major
      unanswered question. Further, whether the primary target of oxidative stress and
      damage is photoreceptors or RPE cells, or both, is still unclear. In this review,
      we discuss the major functions of RPE cells with an emphasis on the oxidative
      challenges these cells encounter and the endogenous antioxidant mechanisms
      employed to neutralize the deleterious effects that such stresses can elicit if
      left unchecked.

PMID- 22878109
TI  - Determination of radioactivity and heavy metals of Bakircay river in Western
      Turkey.
AB  - In this study, radioactive and heavy metal contaminations in sediments and waters
      of Bakircay River in Western Turkey were investigated to determine their
      pollution potential. The radium concentrations in the water samples were measured
      using the collector-chamber method. The radioactivities of (40)K, (226)Ra and
      (232)Th in sediments and soils were found to be 45.30 to 839.19 Bq kg(-1), 35.26
      to 160.57 Bq kg(-1) and 1.86 to 131.49 Bq kg(-1), respectively. The activity of
      (226)Ra in the water samples ranged from 0.09 to 0.36 Bq/L. To determine the
      radiological hazard of natural radioactivity in the samples, the external
      terrestrial gamma dose rate in air (n Gyh(-1)), annual effective dose rate (mSv
      y(-1)), radium equivalent activity (Bq kg(-1)) were calculated and compared with
      internationally recommended values.

PMID- 22878110
TI  - Transient hypothyroidism at 3-year follow-up among cases of congenital
      hypothyroidism detected by newborn screening.
AB  - OBJECTIVE: To investigate the rate of transient thyroid deficiency and treatment
      compliance among cases with congenital hypothyroidism diagnosed and followed-up
      after age 3 years by newborn screening (NBS). STUDY DESIGN: Cases detected by
      Michigan NBS between October 1, 2003, and December 31, 2007, and followed-up
      after age 3 years were included. The chi(2) and Fisher exact tests were used to
      test differences among followed and lost cases. Logistic regression models were
      used to investigate predictors of treatment cessation. RESULTS: Roughly 45% of
      eligible cases were lost to follow-up, and disease state (transient or permanent
      congenital hypothyroidism) could not be determined for 12 cases (7.9%). Of the 72
      followed cases, 34 (47%) were considered permanent congenital hypothyroidism
      based on thyroid imaging findings (n = 7) or an increase in medication dosage
      over time (n = 27). One-quarter of followed cases with congenital hypothyroidism
      were no longer being treated, and of these, just over 83% stopped treatment
      without medical supervision. Of 23 cases that underwent a medically supervised
      trial without thyroid hormone medication, treatment was reinstated in 20.
      Laboratory confirmation of euthyroidism was available for 6 of 18 cases
      clinically deemed transient. After adjustment, black race was the strongest
      predictor of treatment cessation (OR, 9.86; 95% CI, 1.82-53.31). Treatment
      cessation was also more common among low birth weight infants and those admitted
      to the neonatal intensive care unit at birth. CONCLUSION: We recommend that NBS
      programs include long-term follow-up through at least age 3 years to determine
      treatment compliance and disease permanence. Further research is needed to
      determine ideal follow-up program operations and reassessment methods for
      congenital hypothyroidism disease permanence. Guidelines that provide evidence
      based reassessment methods would be beneficial for the healthcare providers of
      children with congenital hypothyroidism.

PMID- 22878111
TI  - Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants
      with prolonged exposure to intravenous lipids.
AB  - OBJECTIVE: To report changes in red blood cell long-chain polyunsaturated fatty
      acids levels in extremely low birth weight (ELBW) infants relative to duration of
      intravenous lipid emulsion. STUDY DESIGN: Serial blood samples were collected
      from 26 ELBW infants during the first 2 months of life in the neonatal intensive
      care unit using a prospective cohort study design. The primary outcome was the
      change in long-chain polyunsaturated fatty acids levels over the study period
      relative to a duration of intravenous lipid emulsion of either <= 28 days or >28
      days. Secondary outcomes included parenteral and enteral nutritional exposures as
      well as prematurity-associated morbidities. Longitudinal regression estimated
      changes in fatty acid levels between the 2 exposure groups. RESULTS: Infants with
      >28 days intravenous lipid emulsion had 36 more days of intravenous lipid
      emulsion than did those with <= 28 days (P < .001). Docosahexaenoic acid
      significantly decreased over time in all infants and decreased significantly more
      in infants exposed to intravenous lipid emulsion for >28 days (P = .03).
      Arachidonic acid significantly decreased over the study period but the decrease
      was not related to intravenous lipid emulsion duration. Linoleic and alpha
      linolenic acids had significantly larger increases over time in those with longer
      exposure to intravenous lipid emulsion (P < .01). CONCLUSION: Docosahexaenoic
      acid status of ELBW infants declined significantly in the first 2 months of life
      and the decline was significantly greater in those exposed to intravenous lipid
      emulsion >28 days compared with those exposed <= 28 days.

PMID- 22878112
TI  - Prediction of duration of breastfeeding among migrant and Canadian-born women:
      results from a multi-center study.
AB  - OBJECTIVE: To examine and compare predictors of breastfeeding duration among
      migrant and Canadian-born women. STUDY DESIGN: As part of a longitudinal study, a
      sample of 1503 mothers was recruited from 12 hospitals in Canada who completed
      questionnaires at 1 and 16 weeks postpartum. Following bivariate analysis,
      multivariate logistic regression analyses were completed to examine and compare
      predictors of continued breastfeeding at 16 weeks postpartum among migrant and
      Canadian-born women. RESULTS: Among migrant women, factors predictive of
      breastfeeding duration included maternal age >= 35 years, primiparity, and breast
      engorgement pain at 1 week postpartum. Factors predictive of discontinued
      breastfeeding in this group included maternal age <20 years, higher gender
      related development index of country of origin, no previous breastfeeding
      experience, breastfeeding duration of peers <6 months, planned duration of
      exclusive breastfeeding <6 months, and not exclusively breastfeeding at 1 week
      postpartum. Among Canadian-born women, factors predictive of breastfeeding
      duration included residence in Vancouver and maternal age >= 35 years. Factors
      predictive of discontinued breastfeeding included residence in Toronto, maternal
      age <20 years, smoking at 16 weeks postpartum, primiparity, planned duration of
      exclusive breastfeeding <6 months, and not exclusively breastfeeding at 1 week
      postpartum. CONCLUSIONS: Although certain predictors for breastfeeding duration
      were similar between migrant and Canadian-born women, several were dissimilar,
      suggesting that these groups might benefit from different strategies to optimize
      breastfeeding outcomes.

PMID- 22878114
TI  - Do stimulants reduce the risk for cigarette smoking in youth with attention
      deficit hyperactivity disorder? A prospective, long-term, open-label study of
      extended-release methylphenidate.
AB  - OBJECTIVE: Although attention-deficit hyperactivity disorder (ADHD) is a well
      known risk factor for cigarette smoking, prospective studies aimed at reducing
      smoking risk in this population are critically needed. STUDY DESIGN: This was a 2
      year, prospective, open-label clinical trial of extended-release methylphenidate
      for smoking prevention in adolescents with ADHD (n = 154). Smoking outcomes were
      assessed with the Fagerstrom Tolerance Questionnaire. Comparisons were made using
      data from a historical, naturalistic sample of ADHD (n = 103) and non-ADHD
      comparators (n = 188) of similar age and sex assessed with the same assessment
      battery as that used in subjects participating in the clinical trial. RESULTS:
      The smoking rate at endpoint (mean, 10 months of methylphenidate treatment) was
      low in the clinical trial subjects and not significantly different from that in
      the non-ADHD comparators or the ADHD comparators receiving stimulants
      naturalistically (7.1% vs 8.0% vs 10.9%; P > .20). In contrast, the smoking rate
      was significantly lower in the clinical trial subjects than in the naturalistic
      sample of ADHD comparators who were not receiving stimulant treatment (7.1% vs
      19.6%; P = .009 [not significant], adjusting for comorbid conduct disorder and
      alcohol and drug abuse). CONCLUSION: Although considered preliminary until
      replicated in future randomized clinical trials, the findings from this single
      site, open-label study suggest that stimulant treatment may contribute to a
      decreased risk for smoking in adolescents with ADHD. If confirmed, this finding
      would have significant clinical and public health impacts.

PMID- 22878113
TI  - Subtypes of preterm birth and the risk of postneonatal death.
AB  - OBJECTIVE: To examine the differences in postneonatal death risk among 3 clinical
      subtypes of preterm birth: preterm premature rupture of membranes (PROM),
      indicated preterm birth, and spontaneous preterm labor. STUDY DESIGN: We analyzed
      the 2001-2005 US linked birth/infant death (birth cohort) datasets. The preterm
      birth subtypes were classified using information on the birth certificate:
      reported PROM, induction of labor, cesarean section, and complications of
      pregnancy and labor. Cox proportional hazard models were used to estimate
      covariate-adjusted hazard ratios and 95% CIs for postneonatal death (from days 28
      to 365). Estimation was given for preterm birth subtypes in a week-by-week
      analysis. Causes of death were analyzed by preterm birth subtype and then
      separately at 24-27, 28-31, and 32-36 weeks of gestation. RESULTS: For the total
      of 1895350 singleton preterm births who survived the neonatal period, the
      postneonatal mortality rate was 1.11% for preterm PROM, 0.78% for indicated
      preterm birth, and 0.53% for spontaneous preterm labor. Preterm PROM was
      associated with significantly higher risk of postneonatal death compared with
      spontaneous preterm labor in infants born at 27 weeks gestation or later.
      Similarly, indicated preterm birth was associated with a significantly higher
      risk of postneonatal death than spontaneous preterm labor in infants born at 25
      weeks gestation or later. Preterm PROM and indicated preterm birth were
      associated with greater risk of death in the postneonatal period compared with
      spontaneous preterm labor, irrespective of the cause of death. CONCLUSION:
      Subtypes of preterm birth carry different risks of postneonatal mortality.
      Prevention of preterm-related postneonatal death may require more research into
      the root causes of preterm birth subtypes.

PMID- 22878115
TI  - Risk factors for and outcomes of acute kidney injury in neonates undergoing
      complex cardiac surgery.
AB  - OBJECTIVE: To characterize the epidemiology of and identify risk factors for
      neonatal cardiac surgery-associated acute kidney injury (CS-AKI) and determine
      its impact on clinical outcomes. STUDY DESIGN: Using secondary analysis of data
      from an ongoing multiprovincial prospective cohort study, we studied 264 neonates
      undergoing complex cardiac repair. CS-AKI was defined based on the Acute Kidney
      Injury Network (AKIN) definition. We used regression modeling and survival
      analysis (adjusting for covariates) to evaluate associations. RESULTS: CS-AKI
      occurred in 64% of the neonates in our study cohort. Lower age, longer
      cardiopulmonary bypass time, hypothermic circulatory arrest, type of repair,
      lower preoperative serum creatinine (SCr) level, lower gestational age, and
      preoperative ventilation were independent risk factors for developing CS-AKI.
      Neonates with CS-AKI had longer times to extubation, intensive care discharge,
      and hospital discharge, after adjusting for covariates. Mortality was
      significantly increased in neonates with AKIN stage 2 or higher CS-AKI. The
      neonates with CS-AKI had a lower z-score for height at 2-year follow-up and were
      seen by more specialists. CONCLUSION: Neonatal CS-AKI is common and independently
      predicts important clinical outcomes, including mortality. Many risk factors are
      similar to those in older children, but some are unique to neonates. The
      observation that lower baseline SCr predicts CS-AKI merits further study. The
      AKIN definition, based on preoperative SCr value, is a reasonable method for
      defining CS-AKI in neonates. Many previous studies of CS-AKI have excluded
      neonates; we suggest that future intervention studies on approaches to reducing
      CS-AKI incidence and improving outcomes should include neonates.

PMID- 22878108
TI  - Cell biology of ischemia/reperfusion injury.
AB  - Disorders characterized by ischemia/reperfusion (I/R), such as myocardial
      infarction, stroke, and peripheral vascular disease, continue to be among the
      most frequent causes of debilitating disease and death. Tissue injury and/or
      death occur as a result of the initial ischemic insult, which is determined
      primarily by the magnitude and duration of the interruption in the blood supply,
      and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP
      levels and intracellular pH decrease as a result of anaerobic metabolism and
      lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms
      become dysfunctional, contributing to increased intracellular and mitochondrial
      calcium levels (calcium overload), cell swelling and rupture, and cell death by
      necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen
      levels are restored upon reperfusion, a surge in the generation of reactive
      oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues
      to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate
      the opening of the mitochondrial permeability transition pore, which appears to
      represent a common end-effector of the pathologic events initiated by I/R. The
      aim of this treatise is to provide a comprehensive review of the mechanisms
      underlying the development of I/R injury, from which it should be apparent that a
      combination of molecular and cellular approaches targeting multiple pathologic
      processes to limit the extent of I/R injury must be adopted to enhance resistance
      to cell death and increase regenerative capacity in order to effect long-lasting
      repair of ischemic tissues.

PMID- 22878116
TI  - Embodied attention and word learning by toddlers.
AB  - Many theories of early word learning begin with the uncertainty inherent to
      learning a word from its co-occurrence with a visual scene. However, the relevant
      visual scene for infant word learning is neither from the adult theorist's view
      nor the mature partner's view, but is rather from the learner's personal view.
      Here we show that when 18-month old infants interacted with objects in play with
      their parents, they created moments in which a single object was visually
      dominant. If parents named the object during these moments of bottom-up
      selectivity, later forced-choice tests showed that infants learned the name, but
      did not when naming occurred during a less visually selective moment. The
      momentary visual input for parents and toddlers was captured via head cameras
      placed low on each participant's forehead as parents played with and named
      objects for their infant. Frame-by-frame analyses of the head camera images at
      and around naming moments were conducted to determine the visual properties at
      input that were associated with learning. The analyses indicated that learning
      occurred when bottom-up visual information was clean and uncluttered. The sensory
      motor behaviors of infants and parents were also analyzed to determine how their
      actions on the objects may have created these optimal visual moments for
      learning. The results are discussed with respect to early word learning, embodied
      attention, and the social role of parents in early word learning.

PMID- 22878117
TI  - Grey parrot number acquisition: the inference of cardinal value from ordinal
      position on the numeral list.
AB  - A Grey parrot (Psittacus erithacus) had previously been taught to use English
      count words ("one" through "sih" [six]) to label sets of one to six individual
      items (Pepperberg, 1994). He had also been taught to use the same count words to
      label the Arabic numerals 1 through 6. Without training, he inferred the
      relationship between the Arabic numerals and the sets of objects (Pepperberg,
      2006b). In the present study, he was then trained to label vocally the Arabic
      numerals 7 and 8 ("sih-none", "eight", respectively) and to order these Arabic
      numerals with respect to the numeral 6. He subsequently inferred the ordinality
      of 7 and 8 with respect to the smaller numerals and he inferred use of the
      appropriate label for the cardinal values of seven and eight items. These data
      suggest that he constructed the cardinal meanings of "seven" ("sih-none") and
      "eight" from his knowledge of the cardinal meanings of one through six, together
      with the place of "seven" ("sih-none") and "eight" in the ordered count list.

PMID- 22878118
TI  - Intensity-modulated radiation therapy and volumetric-modulated arc therapy for
      adult craniospinal irradiation--a comparison with traditional techniques.
AB  - Craniospinal irradiation (CSI) poses a challenging planning process because of
      the complex target volume. Traditional 3D conformal CSI does not spare any
      critical organs, resulting in toxicity in patients. Here the dosimetric
      advantages of intensity-modulated radiation therapy (IMRT) and volumetric
      modulated arc therapy (VMAT) are compared with classic conformal planning in
      adults for both cranial and spine fields to develop a clinically feasible
      technique that is both effective and efficient. Ten adult patients treated with
      CSI were retrospectively identified. For the cranial fields, 5-field IMRT and
      dual 356 degrees  VMAT arcs were compared with opposed lateral 3D conformal
      radiotherapy (3D-CRT) fields. For the spine fields, traditional posterior
      anterior (PA) PA fields were compared with isocentric 5-field IMRT plans and
      single 200 degrees  VMAT arcs. Two adult patients have been treated using this
      IMRT technique to date and extensive quality assurance, especially for the
      junction regions, was performed. For the cranial fields, the IMRT technique had
      the highest planned target volume (PTV) maximum and was the least efficient,
      whereas the VMAT technique provided the greatest parotid sparing with better
      efficiency. 3D-CRT provided the most efficient delivery but with the highest
      parotid dose. For the spine fields, VMAT provided the best PTV coverage but had
      the highest mean dose to all organs at risk (OAR). 3D-CRT had the highest PTV and
      OAR maximum doses but was the most efficient. IMRT provides the greatest OAR
      sparing but the longest delivery time. For those patients with unresectable
      disease that can benefit from a higher, definitive dose, 3D-CRT-opposed laterals
      are the most clinically feasible technique for cranial fields and for spine
      fields. Although inefficient, the IMRT technique is the most clinically feasible
      because of the increased mean OAR dose with the VMAT technique. Quality assurance
      of the beams, especially the junction regions, is essential.

PMID- 22878119
TI  - Effects of progestins on local estradiol biosynthesis and action in the Z-12
      endometriotic epithelial cell line.
AB  - Endometriosis is a common estrogen-dependent gynecological disease. In patients
      with endometriosis estradiol can be synthesized locally in the endometriotic
      lesions from inactive precursors of adrenal or ovarian origin, via the aromatase
      pathway. These increased estradiol levels stimulate proliferation of
      endometriotic tissue. The progestins have been used in the therapy of
      endometriosis for more than 40 years but their pharmacological action is still
      not understood in detail. In the present study we therefore aimed to evaluate the
      effects of three progestins most commonly used in the therapy of endometriosis;
      medroxyprogesterone acetate, dydrogesterone and dienogest on expression of all
      genes encoding enzymes of the aromatase pathway and estrogen receptors in the Z
      12 model epithelial cell line of peritoneal endometriosis, by qPCR and Western
      blotting. Our results show that application of medroxyprogestrone acetate,
      dydrogesterone and dienogest significantly decreases HSD17B1 and CYP19A1
      expression and significantly increases HSD17B2 expression. Dydrogesterone and
      dienogest also significantly suppress ESR1 and ESR2 transcription, whereas
      medroxyprogestrone acetate and dydrogesterone significantly reduce mRNA levels of
      GPER. Our results thus suggest that in peritoneal endometriosis the beneficial
      effects of these progestins can be explained by lower HSD17B1 and higher HSD17B2
      mRNA and protein levels, which lead to reduced local E2 biosynthesis. Although
      progestins significantly decrease CYP19A1 mRNA levels, the protein itself was not
      detectable by Western blotting. As progestins down-regulate expression of ESR1,
      ESR2 and GPER, they might also prevent E2-mediated proliferation.

PMID- 22878120
TI  - Cytochrome b(5) forms homomeric complexes in living cells.
AB  - Cytochrome b(5) (cyt-b(5)) is a ubiquitous hemoprotein also associated with
      microsomal cytochrome P450 17alpha-hydroxylase/17,20 lyase (CYP17A1). In the
      steroidogenic pathway CYP17A1 catalyses the metabolism of pregnenolone, yielding
      both glucocorticoid and androgen precursors. While not affecting the 17alpha
      hydroxylation of pregnenolone, cyt-b(5) augments the 17,20 lyase reaction of 17
      hydroxypregnenolone, catalyzing the formation of DHEA, through direct protein
      protein interactions. In this study, multimeric complex formation of cyt-b(5) and
      the possible regulatory role of these complexes were investigated. Cyt-b(5) was
      isolated from ovine liver and used to raise anti-sheep cyt-b(5) immunoglobulins.
      Immunochemical studies revealed that, in vivo, cyt-b(5) is primarily found in the
      tetrameric form. Subsequent fluorescent resonance energy transfer (FRET) studies
      in COS-1 cells confirmed the formation of homomeric complexes by cyt-b(5) in live
      cells. Site-directed mutagenesis revealed that the C-terminal linker domain of
      cyt-b(5) is vital for complex formation. The 17,20-lyase activity of CYP17 was
      augmented by truncated cyt-b(5), which is unable to form complexes when co
      expressed in COS-1 cells, thereby implicating the monomeric form of cyt-b(5) as
      the active species. This study has shown for the first time that cyt-b(5) forms
      homomeric complexes in vivo, implicating complex formation as a possible
      regulatory mechanism in steroidogenesis.

PMID- 22878122
TI  - Enteric glia and neuroprotection: basic and clinical aspects.
AB  - The enteric nervous system (ENS), a major regulatory system for gastrointestinal
      function, is composed of neurons and enteric glial cells (EGCs). Enteric glia
      have long been thought to provide only structural support to neurons. However,
      recent evidence indicates enteric glia-neuron cross talk significantly
      contributes to neuronal maintenance, survival, and function. Thus damage to EGCs
      may trigger neurodegenerative processes thought to play a role in
      gastrointestinal dysfunctions and symptoms. The purpose of this review is to
      provide an update on EGCs, particularly focusing on their possible
      neuroprotective features and the resultant enteric neuron abnormalities
      subsequent to EGC damage. These neuroprotective mechanisms may have pathogenetic
      relevance in a variety of functional and inflammatory gut diseases. Basic and
      clinical (translational) studies support a neuroprotective role mediated by EGCs.
      Different models have been developed to test whether selective EGC
      damage/ablation has an impact on gut functions and the ENS. Preclinical data
      indicated that selective EGC alterations were associated with changes in gut
      physiology related to enteric neuron abnormalities. In humans, a substantial loss
      of EGCs was described in patients with various functional and/or inflammatory
      gastrointestinal diseases. However, whether EGC changes precede or follow
      neuronal degeneration and loss and how this damage occurs is not defined.
      Additional studies on EGC neuroprotective capacity are expected to improve
      knowledge of gut diseases and pave the way for targeted therapeutic strategies of
      underlying neuropathies.

PMID- 22878123
TI  - Functional TRPV6 channels are crucial for transepithelial Ca2+ absorption.
AB  - TRPV6 is considered the primary protein responsible for transcellular Ca2+
      absorption. In vitro studies demonstrate that a negatively charged amino acid (D)
      within the putative pore region of mouse TRPV6 (position 541) is critical for
      Ca2+ permeation of the channel. To elucidate the role of TRPV6 in transepithelial
      Ca2+ transport in vivo, we functionally analyzed a TRPV6D541A/D541A knockin mouse
      model. After weaning, mice were fed a regular (1% wt/wt) or Ca2+-deficient (0.02%
      wt/wt) diet and housed in metabolic cages. Blood was sampled for Ca2+
      measurements, and the expression of Ca2+ transport proteins was analyzed in
      kidney and duodenum. Intestinal 45Ca2+ uptake was measured in vivo by an
      absorption assay. Challenging the mice with the Ca2+-deficient diet resulted in
      hypocalcemia in wild-type and TRPV6D541A/D541A mice. On a low-Ca2+ diet both
      mouse strains displayed increased expression of intestinal TRPV6, calbindin
      D(9K), and renal TRPV5. TRPV6D541A/D541A mice showed significantly impaired
      intestinal Ca2+ uptake compared with wild-type mice, and duodenal TRPV5
      expression was increased in TRPV6D541A/D541A mice. On a normal diet, serum Ca2+
      concentrations normalized in both mouse strains. Under these conditions,
      intestinal Ca2+ uptake was similar, and the expression levels of renal and
      intestinal Ca2+ transport proteins were not affected. We demonstrate that
      TRPV6D541A/D541A mice exhibit impaired transcellular Ca2+ absorption. Duodenal
      TRPV5 expression was increased in TRPV6D541A/D541A mice, albeit insufficient to
      correct for the diminished Ca2+ absorption. Under normal conditions, when passive
      Ca2+ transport is predominant, no differences between wild-type and
      TRPV6D541A/D541A mice were observed. Our results demonstrate a specific role for
      TRPV6 in transepithelial Ca2+ absorption.

PMID- 22878121
TI  - Animal models of intestinal fibrosis: new tools for the understanding of
      pathogenesis and therapy of human disease.
AB  - Fibrosis is a serious condition complicating chronic inflammatory processes
      affecting the intestinal tract. Advances in this field that rely on human studies
      have been slow and seriously restricted by practical and logistic reasons. As a
      consequence, well-characterized animal models of intestinal fibrosis have emerged
      as logical and essential systems to better define and understand the
      pathophysiology of fibrosis. In point of fact, animal models allow the execution
      of mechanistic studies as well as the implementation of clinical trials with
      novel, pathophysiology-based therapeutic approaches. This review provides an
      overview of the currently available animal models of intestinal fibrosis, taking
      into consideration the methods of induction, key characteristics of each model,
      and underlying mechanisms. Currently available models will be classified into
      seven categories: spontaneous, gene-targeted, chemical-, immune-, bacteria-, and
      radiation-induced as well as postoperative fibrosis. Each model will be discussed
      in regard to its potential to create research opportunities to gain insights into
      the mechanisms of intestinal fibrosis and stricture formation and assist in the
      development of effective and specific antifibrotic therapies.

PMID- 22878124
TI  - Serological and virological BVDV prevalence and risk factor analysis for herds to
      be BVDV seropositive in Belgian cattle herds.
AB  - Bovine viral diarrhoea virus (BVDV) is a worldwide spread virus that most
      commonly infects cattle and can cause considerable economic losses. To determine
      the prevalence of BVDV in Belgium, a cross-sectional study was performed between
      November 2009 and March 2010. Young stock aged between 6 and 12 months from 773
      randomly selected Belgian cattle herds were tested for BVDV-specific antibodies
      and antigen. With a target and maximum of 10 animals per sampled herd, a total of
      5246 animals were selected. Additionally a questionnaire including different herd
      management topics and questions about participation in animal health programmes,
      including BVDV, was sent to 1100 Belgian cattle herds, including the 773 herds
      for BVDV testing. This paper focuses on results regarding these 773 herds. The
      true prevalence of BVDV-specific antibodies and antigen at herd level was
      respectively 47.4% and 4.4%, while at animal level this was respectively 32.9%
      and 0.3%. In 44.4% of the herds where BVDV-specific antibodies were detected at
      least 60% of the sampled young stock was BVDV seropositive. Interestingly, 83.4%
      of these farmers stated not to have suffered from problems related to BVDV.
      Moreover, only 8.4% of all farmers who completed the questionnaire (n=895)
      reported problems possibly related to BVDV the past 3 years. This demonstrates
      that farmers are often unaware of the presence of BVDV in their herd. Risk
      factors for a herd to be BVDV seropositive were identified by means of a
      multivariable logistic regression model. Large herds were significantly more
      likely to be BVDV seropositive (OR=1.004, p<0.01). The interaction between
      "Antigen positive animal detected in this study" and "BVDV vaccination in 2009"
      was significant (p<0.01). In non-vaccinating herds, the detection of antigen
      positive animals was significantly associated with BVDV seropositive herds
      (OR=13.8, p<0.01). In herds with no antigen positive animals detected,
      vaccination resulted in a significant risk factor to be BVDV seropositive
      compared to non-vaccinating herds (OR=3.4, p<0.01). Herds reporting BVDV-related
      problems the past 3 years were more likely to be BVDV seropositive (OR=1.9,
      p<0.05). This relation became non-significant (OR=1.8, p=0.08) when only a subset
      of herds with no vaccination of animals <12 months was taken into account. The
      results of the current study suggest an active circulation of BVDV in a
      considerable number of Belgian cattle herds.

PMID- 22878125
TI  - Colonization pressure and risk factors for acquisition of imipenem-resistant
      Acinetobacter baumannii in a medical surgical intensive care unit in Brazil.
AB  - We studied a nonconcurrent cohort of 582 patients admitted to a medical-surgical
      intensive care unit. Use of antimicrobials (imipenem and metronidazole) was a
      risk factor for acquisition of imipenem-resistant Acinetobacter baumannii only
      for the subcohort of patients admitted in months in which colonization pressure
      was lower than the median value.

PMID- 22878126
TI  - Toward semi-automated assessment of target volume delineation in radiotherapy
      trials: the SCOPE 1 pretrial test case.
AB  - PURPOSE: To evaluate different conformity indices (CIs) for use in the analysis
      of outlining consistency within the pretrial quality assurance (Radiotherapy
      Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial
      of esophageal cancer and to make recommendations for their use in future trials.
      METHODS AND MATERIALS: The National Cancer Research Institute SCOPE 1 trial is an
      ongoing Cancer Research UK-funded phase II/III randomized controlled trial of
      chemoradiation with capecitabine and cisplatin with or without cetuximab for
      esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy
      protocol, an educational package, and a single mid-esophageal tumor test case
      that were sent to each investigator to outline. Investigator gross tumor volumes
      (GTVs) were received from 50 investigators in 34 UK centers, and CERR
      (Computational Environment for Radiotherapy Research) was used to perform an
      assessment of each investigator GTV against a predefined gold-standard GTV using
      different CIs. A new metric, the local conformity index (l-CI), that can localize
      areas of maximal discordance was developed. RESULTS: The median Jaccard
      conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50
      investigators (28%) achieving a JCI of 0.7 or greater. The median geographical
      miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance
      index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the
      middle section of the volume, where the tumor was bulky and more easily
      definable, and identified 4 slices where fewer than 20% of investigators achieved
      an l-CI of 0.7 or greater. CONCLUSIONS: The available CIs analyze different
      aspects of a gold standard-observer variation, with JCI being the most useful as
      a single metric. Additional information is provided by the l-CI and can focus the
      efforts of the RTTQA team in these areas, possibly leading to semi-automated
      outlining assessment.

PMID- 22878127
TI  - Impact of internal metallic ports in temporary tissue expanders on postmastectomy
      radiation dose distribution.
AB  - PURPOSE: Temporary tissue expanders (TTE) with an internal magnetic metal port
      (IMP) have been increasingly used for breast reconstruction in post-mastectomy
      patients who receive radiation therapy (XRT). We evaluated XRT plans of patients
      with IMP to determine its effect on XRT dose distribution. METHODS AND MATERIALS:
      Original treatment plans with CT simulation scans of 24 consecutive patients who
      received XRT (ORI), planned without heterogeneity corrections, to a reconstructed
      breast containing an IMP were used. Two additional treatment plans were then
      generated: one treatment plan with the IMP assigned the electron density of the
      rare earth magnet, nickel plated neodymium-iron-boron (HET), and a second
      treatment plan with the IMP assigned a CT value of 1 to simulate a homogeneous
      breast without an IMP (BRS). All plans were prescribed 50 Gy to the reconstructed
      breast (CTV). RESULTS: CTV coverage by 50 Gy was significantly lower in the HET
      (mean 87.7% CTV) than in either the ORI (mean 99.7% CTV, P<.001) or BRS plans
      (mean 95.0% CTV, P<.001). The effect of the port was more pronounced on CT slices
      containing the IMP with prescription dose coverage of the CTV being less in the
      HET than in either ORI (mean difference 33.6%, P<.01) or BRS plans (mean
      difference 30.1%, P<.001). HET had a less homogeneous and conformal dose
      distribution than BRS or ORI. CONCLUSION: IMPs increase dose heterogeneity and
      reduce dose to the breast CTV through attenuation of the beam. For optimal XRT
      treatment, heterogeneity corrections should be used in XRT planning for patients
      with TTE with IMP, as the IMP impacts dose distribution.

PMID- 22878129
TI  - Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium
      falciparum.
AB  - Polyamines and the enzymes involved in their biosynthesis are present at high
      levels in rapidly proliferating cells, including cancer cells and protozoan
      parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria
      parasites causes cytostatic arrest of parasite development under in vitro
      conditions, but does not cure infections in vivo. This may be due to
      replenishment of the parasite's intracellular polyamine pool via salvage of
      exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake
      by the intraerythrocytic parasite are not well understood. In this study, the
      uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum
      parasites functionally isolated from their host erythrocyte was investigated
      using radioisotope flux techniques. Both putrescine and spermidine were taken up
      into isolated parasites via a temperature-dependent process that showed cross
      competition between different polyamines. There was also some inhibition of
      polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led
      to an increase in the total amount of putrescine and spermidine taken up from the
      extracellular medium. The uptake of putrescine and spermidine by isolated
      parasites was independent of extracellular Na(+) but increased with increasing
      external pH. Uptake also showed a marked dependence on the parasite's membrane
      potential, decreasing with membrane depolarization and increasing with membrane
      hyperpolarization. The data are consistent with polyamines being taken up into
      the parasite via an electrogenic uptake process, energised by the parasite's
      inwardly negative membrane potential.

PMID- 22878128
TI  - Structural architecture and interplay of the nucleotide- and erythrocyte binding
      domain of the reticulocyte binding protein Py235 from Plasmodium yoelii.
AB  - Human malaria is caused by the cyclical invasion of the host's red blood cells
      (RBCs) by the invasive form of the parasite, the merozoite. The invasion of the
      RBC involves a range of parasite ligand receptor interactions, a process which is
      under intensive investigation. Two protein families are known to be important in
      the recognition and invasion of the human erythrocyte, the erythrocyte-binding
      like (EBL) proteins and the reticulocyte binding like proteins, of which the
      Py235 family in Plasmodium yoelii is a member. Recently the nucleotide binding
      domain (NBD94), that plays a role in ATP sensing, and the erythrocyte binding
      domain (EBD) of Py235, called EBD(1-194), have been identified. Binding of ATP
      leads to conformational changes within Py235 from P. yoelli and results in
      enhanced binding of the protein to the RBC. Structural features of these domains
      have been obtained, providing the platform to discuss how the structural
      architecture creates the basis for an interplay of the sensing NBD and the EBD
      domain in Py235. In analogy to the receptor-mediated ligand-dimerization model of
      the EBL proteins PvDBP and PfEBA-175 from Plasmodium vivax and Plasmodium
      falciparum, respectively, we hypothesise that Py235 of P. yoelii binds via its
      EBD(1-194) domain to the RBC receptor, thereby inducing dimerization of the Py235
      receptor complex.

PMID- 22878130
TI  - Behavioural and cognitive effects during vagus nerve stimulation in children with
      intractable epilepsy - a randomized controlled trial.
AB  - BACKGROUND/AIMS: In addition to effects on seizure frequency in intractable
      epilepsy, multiple studies report benefits of vagus nerve stimulation (VNS) on
      behavioural outcomes and quality of life. The present study aims to investigate
      the effects of VNS on cognition, mood in general, depression, epilepsy-related
      restrictions and psychosocial adjustment in children with intractable epilepsy,
      as well as the relation between these effects and seizure reduction. METHODS: We
      conducted a randomized, active-controlled, double-blinded, add-on study in 41
      children (age 4-18) with medically refractory epilepsy. We performed cognitive
      and behavioural testing at baseline (12 weeks), at the end of the blinded phase
      (20 weeks) in children receiving either high-output or low-output (active
      control) stimulation, and at the end of the open label phase (19 weeks) with all
      children receiving high-output stimulation. Seizure frequency was recorded using
      seizure diaries. RESULTS: VNS did not have a negative effect on cognition nor on
      psychosocial adjustment. At the end of the follow-up phase we noted an
      improvement of mood in general and the depression subscale for the entire group,
      unrelated to a reduction of seizure frequency. At the end of the blinded phase a
      >=50% reduction of seizure frequency occurred in 16% of the high-stimulation
      group and 21% of the low-stimulation group. At the end of the open-label follow
      up phase, 26% of the children experienced a seizure frequency reduction of 50% or
      more (responders). CONCLUSIONS: VNS has additional beneficial effects in children
      with intractable epilepsy. As opposed to anti-epileptic drugs, there are no
      negative effects on cognition. Moreover, we observed an improvement of mood in
      general and depressed feelings in particular, irrespective of a reduction in
      seizure frequency. These beneficial effects should be taken into account when
      deciding whether to initiate or continue VNS treatment in these children.

PMID- 22878131
TI  - Political violence and mental health in Nepal: prospective study.
AB  - BACKGROUND: Post-conflict mental health studies in low-income countries have
      lacked pre-conflict data to evaluate changes in psychiatric morbidity resulting
      from political violence. AIMS: This prospective study compares mental health
      before and after exposure to direct political violence during the People's War in
      Nepal. METHOD: An adult cohort completed the Beck Depression Inventory and Beck
      Anxiety Inventory in 2000 prior to conflict violence in their community and in
      2007 after the war. RESULTS: Of the original 316 participants, 298 (94%)
      participated in the post-conflict assessment. Depression increased from 30.9 to
      40.6%. Anxiety increased from 26.2 to 47.7%. Post-conflict post-traumatic stress
      disorder (PTSD) was 14.1%. Controlling for ageing, the depression increase was
      not significant. The anxiety increase showed a dose-response association with
      conflict exposure when controlling for ageing and daily stressors. No demographic
      group displayed unique vulnerability or resilience to the effects of conflict
      exposure. CONCLUSIONS: Conflict exposure should be considered in the context of
      other types of psychiatric risk factors. Conflict exposure predicted increases in
      anxiety whereas socioeconomic factors and non-conflict stressful life events were
      the major predictors of depression. Research and interventions in post-conflict
      settings therefore should consider differential trajectories for depression v.
      anxiety and the importance of addressing chronic social problems ranging from
      poverty to gender and ethnic/caste discrimination.

PMID- 22878132
TI  - Prevalence of attention-deficit hyperactivity disorder in older adults in The
      Netherlands.
AB  - BACKGROUND: Little is known about the prevalence of attention-deficit
      hyperactivity disorder (ADHD) among older adults. AIMS: To estimate the
      prevalence of the syndromatic and symptomatic DSM-IV ADHD diagnosis in older
      adults in The Netherlands. METHOD: Data were used from the Longitudinal Aging
      Study Amsterdam (LASA). At baseline, 1494 participants were screened with an ADHD
      questionnaire and in 231 respondents a structured diagnostic interview was
      administered. The weighted prevalence of ADHD was calculated. RESULTS: The
      estimated prevalence rate of syndromatic ADHD in older adults was 2.8%; for
      symptomatic ADHD the rate was 4.2%. Younger elderly adults (60-70 years) reported
      significantly more ADHD symptoms than older elderly adults (71-94 years).
      CONCLUSIONS: This is the first epidemiological study on ADHD in older persons.
      With a prevalence of 2.8% the study demonstrates that ADHD does not fade or
      disappear in adulthood and that it is a topic very much worthy of further study.

PMID- 22878133
TI  - Efficacy of mindfulness-based cognitive therapy in relation to prior history of
      depression: randomised controlled trial.
AB  - BACKGROUND: There appears to be consensus that patients with only one or two
      prior depressive episodes do not benefit from treatment with mindfulness-based
      cognitive therapy (MBCT). AIMS: To investigate whether the effect of MBCT on
      residual depressive symptoms is contingent on the number of previous depressive
      episodes (trial number NTR1084). METHOD: Currently non-depressed adults with
      residual depressive symptoms and a history of depression (<=2 prior episodes: n =
      71; >=3 episodes: n = 59) were randomised to MBCT (n = 64) or a waiting list
      (control: n = 66) in an open-label, randomised controlled trial. The main outcome
      measured was the reduction in residual depressive symptoms (Hamilton Rating Scale
      for Depression, HRSD-17). RESULTS: Mindfulness-based cognitive therapy was
      superior to the control condition across subgroups (beta = -0.56, P<0.001). The
      interaction between treatment and subgroup was not significant (beta = 0.45, P =
      0.16). CONCLUSIONS: Mindfulness-based cognitive therapy reduces residual
      depressive symptoms irrespective of the number of previous episodes of major
      depression.

PMID- 22878134
TI  - Nicotine dependence and illness severity in schizophrenia.
AB  - BACKGROUND: Reasons for the increased prevalence of cigarette smoking in
      schizophrenia are unclear. Studies assessing clinical symptoms have sampled
      heterogeneous populations, with discrepant findings. AIMS: To examine the
      relationship between clinical features, social adjustment and nicotine dependence
      in a geographically defined population of people with schizophrenia. METHOD:
      Cross-sectional clinical study of 131 people with schizophrenia in Nithsdale,
      Scotland. RESULTS: Smokers were younger, mostly males and three times more likely
      to be unemployed. Those with severe nicotine dependence had greater scores on the
      positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were
      prescribed higher doses of antipsychotic. Those with mild-moderate dependence had
      greater scores on the PANSS negative subscale. Greater symptom severity was
      associated with poorer social adjustment. Psychopathology and social adjustment
      were similar in quitters and never-smokers. CONCLUSIONS: Our findings indicate an
      association between nicotine dependence, clinical symptoms and social adjustment
      in schizophrenia. Although causal links cannot be inferred, identifying the
      relationship between nicotine dependence and psychopathology may have some value
      in the management of smoking in schizophrenia. Further longitudinal studies are
      required to explore this relationship.

PMID- 22878135
TI  - [Aging of the respiratory system: anatomical changes and physiological
      consequences].
AB  - The respiratory system undergoes progressive involution with age, resulting in
      anatomical and functional changes that are exerted on all levels. The rib cage
      stiffens and respiratory muscles weaken. Distal bronchioles have reduced diameter
      and tend to be collapsed. Mobilized lung volumes decrease with age while residual
      volume increases. Gas exchanges are modified with a linear decrease of PaO(2) up
      to the age of 70 years and a decreased diffusing capacity of carbon monoxide.
      Ventilatory responses to hypercapnia, hypoxia and exercise decrease in the
      elderly. Knowledge of changes in the respiratory system related to advancing age
      is a medical issue of great importance in order to distinguish the effects of
      aging from those of diseases.

PMID- 22878136
TI  - [Pott's disease (about 16 cases)].
AB  - INTRODUCTION: Pott's disease or spinal tuberculosis is rare, but represents the
      most common form of osteo-articular tuberculosis in endemic countries. MATERIAL
      AND METHODS: [corrected] From January 2000 to December 2010, we collected 16
      cases of Pott's disease. We analyzed clinical and radiological profile, means of
      confirmation and treatment. RESULTS: Spinal and chest pain were the most frequent
      signs. Four patients had neurological signs. The diagnosis was made by the
      detection of bacillus in the pus of paravertebral abscess in six cases, by
      histological study of vertebral biopsy in five cases, biopsy of another
      associated lesion in one case and in front of radio-clinical arguments with good
      clinical evolution under antibacillary treatment in four cases. The antibacillary
      treatment associating four drugs was indicated and correctly followed by all
      patients. Surgical drainage was associated in five cases. The evolution was good
      in all cases. DISCUSSION: Diagnosis of Pott's disease is late when there is no
      neurological sign. Imaging allows to make early diagnosis with MRI. Prognosis is
      good when treatment is started early.

PMID- 22878137
TI  - Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response
      in the primary mouse macrophages and mouse models.
AB  - Geniposide, a main iridoid glucoside component of gardenia fruit, has been known
      to exhibit antibacterial, anti-inflammatory and other important therapeutic
      activities. The objective of this study was to investigate the protective effects
      of geniposide on inflammation in lipopolysaccharide (LPS) stimulated primary
      mouse macrophages in vitro and LPS induced lung injury model in vivo. The
      expression of pro-inflammatory cytokines was determined by enzyme-linked
      immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-kappaB), inhibitory kappa
      B (IkappaBalpha) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun
      N-terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by
      Western blot. Further analysis was carried out in mTLR4 and mMD-2 co-transfected
      HEK293 cells. The results showed that geniposide markedly inhibited the LPS
      induced TNF-alpha, IL-6 and IL-1beta production both in vitro and in vivo.
      Geniposide blocked the phosphorylation of IkappaBalpha, p65, p38, ERK and JNK in
      LPS stimulated primary mouse macrophages. Furthermore, geniposide inhibited the
      expression of TLR4 in LPS stimulated primary mouse macrophages and inhibited the
      LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells. In vivo study, it was
      also observed that geniposide attenuated lung histopathologic changes in the
      mouse models. These results suggest that geniposide exerts an anti-inflammatory
      property by down-regulating the expression of TLR4 up-regulated by LPS.
      Geniposide is highly effective in inhibiting acute lung injury and may be a
      promising potential therapeutic reagent for acute lung injury treatment.

PMID- 22878138
TI  - Preventive effect of Imperatorin on acute lung injury induced by
      lipopolysaccharide in mice.
AB  - Imperatorin, a linear furanocoumarin, has many pharmacological effects such as
      antibacterial, anti-inflammatory and antiviral effects. The purpose of this study
      was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced
      acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1h
      before LPS challenge. We found that the levels of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in the
      bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level
      of interleukin-10 (IL-10) was up-regulated 8h after Imperatorin treatment.
      Pretreatment with Imperatorin (15 or 30 mg/kg) decreased lung wet-to-dry weight
      (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO)
      activities. Additionally, Imperatorin attenuated lung histopathological changes
      and significantly inhibited the phosphorylation of IkappaB, JNK, ERK and
      p38/MAPK. These findings demonstrate that Imperatorin protects against LPS
      induced ALI in mice.

PMID- 22878139
TI  - Agaricus brasiliensis-derived beta-glucans exert immunoenhancing effects via a
      dectin-1-dependent pathway.
AB  - Agaricus brasiliensis is a well-known medicinal mushroom. We have previously
      demonstrated that Agaricus-derived polysaccharides exhibit potent antitumor
      effects; however, the underlying mechanism(s) have not been elucidated yet. In
      this study, we examined the immunoenhancing activities of Agaricus extracts.
      Agaricus-derived polysaccharides were characterized as 1,6-beta-glucan with a
      small amount of 1,3-beta-glucan using anti-beta-glucan antibody and nuclear
      magnetic resonance analysis. These polysaccharides strongly induced the
      production of various cytokines from both murine splenocytes and bone marrow
      derived dendritic cells in the presence of exogenous granulocyte-macrophage
      colony-stimulating factor. Polysaccharide-induced cytokine production was
      significantly reduced in bone marrow-derived dendritic cells derived from dectin
      1-deficient mice. Furthermore, a binding assay revealed that the Agaricus-derived
      polysaccharides can be recognized by dectin-1, a pivotal receptor for 1,3-beta
      glucan. Taken together, our results clearly indicate that the immunostimulation
      induced by Agaricus-derived polysaccharides is exerted, at least in part, via
      dectin-1 in combination with granulocyte-macrophage colony-stimulating factor.

PMID- 22878140
TI  - Non homologous end joining-mediated DNA break repair is impaired in B lymphocytes
      of aging mice.
AB  - Aging is an irreversible physiological process characterized by increased risk of
      diseases, reduced effectiveness of vaccines, and decreased immune responses. One
      of the most prominent paradigms of aging and age related conditions is the
      progressive accumulation of un-repaired DNA breaks leading to apoptosis and
      exhaustion of stem cells. Here we hypothesized that B lymphocytes from old mice
      have reduced DNA repair mechanisms as a contributing factor for DNA break
      accumulation. We analyzed class switch recombination (CSR) of naive B lymphocytes
      from old and adult mice to delineate the DNA double strand repair mechanisms
      during aging. In vitro CSR assays and DNA break analysis by labeling
      phosphorylated histone H2AX showed that old mice had significantly reduced DNA
      repair efficiency following DNA breaks. Functional efficiency analysis of DNA
      break repairs using plasmid ligation method showed that B lymphocytes from old
      mice had poor repair efficiency and increased misrepair of linear plasmid.
      Diminished DNA repair in old age can contribute to reduced immune cell repertoire
      and impaired immunity; increased occurrence of cancer; and reduced stem cell
      reserve.

PMID- 22878141
TI  - Speedy skeletal prototype production to help diagnosis in orthopaedic and trauma
      surgery. Methodology and examples of clinical applications.
AB  - As a medical imaging complement, a real 3D replica of the anatomical area of
      interest can be of substantial advantage in orthopaedic and trauma surgery.
      Unlike the 3D virtual, it makes palpable the notion of scale and volume, and
      apparent hidden or ambiguous details and thus enhance or facilitate the diagnosis
      and eventual surgical solutions. CT data of patients, in DICOM3 standard, were
      used for digital 3D reconstruction followed by rapid prototyping (fused
      deposition modelling) of acrylonitrile-butadiene-styrene (ABS) replicas of the
      areas of interest. Three applications were realized: osteotomy for epiphyseal
      malunion, shoulder arthroplasty and femoral trochleoplasty. The actual size
      replicas (obtained in less than thirty hours) provided excellent spatial
      representation with estimation of available bone stock and materialization of
      relief. The process has proven to be appropriate (and economically reasonable),
      including for common cases, when it comes to complex spatial geometry and
      objective representation of the scale of volumes.

PMID- 22878142
TI  - Effects of fall injury type and discharge placement on mortality,
      hospitalization, falls, and ADL changes among older people in Taiwan.
AB  - A longitudinal study was conducted to investigate the effects of injury type and
      discharge placement on mortality, falls, hospital admissions, and changes in
      activities of daily living (ADLs) over a 12-month period among older fallers. Of
      762 community-dwelling people aged 65 years or older who visited an emergency
      department (ED) of a general hospital in Taiwan due to a fall, 273 sustained a
      hip fracture, 157 had a vertebral fracture, 47 had a distal forearm fracture, 102
      had a traumatic brain injury, and 183 had soft-tissue injuries. Results showed
      that, compared to patients with a soft-tissue injury, those with TBI had
      significantly higher risks of dying (rate ratio (RR)=3.59) and hospital
      admissions (RR=3.23) and better improvement in ADLs (1.93 points) at 6 months
      post-injury, and those who sustained a hip fracture (4.26 and 4.41 points), a
      vertebral fracture (3.81 and 3.83 points), or a distal-forearm fracture (2.80 and
      2.80 points) had significantly better improvement in ADLs at 6 and 12 months post
      injury. Patients discharged to a nursing home had a significantly increased risk
      of death (RR=2.08) and hospital admission (RR=2.05) than those returning to their
      usual residence during the first year post-injury. No significant differences in
      the occurrence of falls during the first post-injury year were found among
      patients with different injury types or between those with different discharge
      placements. In conclusion, among the five major fall injury types in older
      people, TBIs result in the highest risk of death and hospital admissions, while
      hip and vertebral fractures exhibited the largest improvement during the first
      year after injury. Additionally, nursing home care may be associated with
      increased risks of death and hospital admissions than home care. In addition to
      primary prevention of falls, further research to investigate mechanisms leading
      to TBIs during a fall is needed to facilitate effective secondary fall-prevention
      programs for older people.

PMID- 22878143
TI  - Evidence that changes in social cognitions predict changes in self-reported
      driver behavior: Causal analyses of two-wave panel data.
AB  - Previous research on the theory of planned behavior (TPB) is characterized by
      cross-sectional tests of the model's proposed causal relationships. In the
      absence of effective experimental techniques for changing the TPB's cognitive
      antecedents, the present research aimed to provide a stronger non-experimental
      test of the model, using causal analyses of two-wave panel data. Two studies of
      driver behavior were conducted in which naturally occurring within-participant
      changes in TPB constructs were measured over time, and used to predict
      corresponding within-participant changes in both intentions and behavior. A two
      wave panel design was used in both studies. Study 1 had a one-month gap between
      baseline and follow-up. At both waves, a convenience sample comprising
      predominantly university students (N=135) completed questionnaire measures of all
      TPB cognitions and behavior (compliance with speed limits in urban areas). Cross
      lagged multiple regressions and bootstrapping procedures for testing multiple
      mediators supported all of the relationships proposed by the TPB. These findings
      were extended in study 2 using a large, non-student sample of speed limit
      offenders (N=1149), a six-month gap between baseline and follow-up, and a larger
      number of cognitive antecedents. Participants completed postal questionnaires at
      both waves to measure all cognitions proposed by the two-component TPB, along
      with moral norm, anticipated regret, self-identity and speeding on urban roads,
      country roads, and fast dual carriageways or motorways. Changes in instrumental
      and affective attitude, descriptive norm, self-efficacy, moral norm, anticipated
      regret and self-identity predicted changes in intention to speed. Changes in
      intention and self-efficacy predicted behavior-change. Injunctive norm and
      perceived controllability did not predict intention or behavior-change.
      Additionally, direct (unhypothesized) relationships with behavior were found for
      affective attitude, descriptive norm and anticipated regret. The implications of
      the findings for theory and the development of effective behavior-change
      interventions are discussed.

PMID- 22878144
TI  - Self-reported and observed risky driving behaviors among frequent and infrequent
      cell phone users.
AB  - The apparently higher crash risk among individuals who use cell phones while
      driving may be due both to the direct interference of cell phone use with the
      driving task and tendencies to engage in risky driving behaviors independent of
      cell phone use. Measurements of actual highway driving performance, self-reported
      aberrant driving behaviors as measured by the Manchester Driver Behavior
      Questionnaire (DBQ), and attitudes toward speeding, passing behaviors and
      relative concern about being involved in a crash were assessed. Individuals who
      reported frequently using cell phones while driving were found to drive faster,
      change lanes more frequently, spend more time in the left lane, and engage in
      more instances of hard braking and high acceleration events. They also scored
      higher in self-reported driving violations on the DBQ and reported more positive
      attitudes toward speeding and passing than drivers who did not report using a
      cell phone regularly while driving. These results indicate that a greater
      reported frequency of cell phone use while driving is associated with a broader
      pattern of behaviors that are likely to increase the overall risk of crash
      involvement. 

PMID- 22878145
TI  - Unintended pregnancies in England in 2010: costs to the National Health Service
      (NHS).
AB  - INTRODUCTION: Here we estimate the direct medical costs to the National Health
      Service (NHS) of unintended pregnancies in 2010 and identify populations at risk
      for unintended pregnancies. METHODS: The number of unintended pregnancies in
      England in 2010 was estimated based on the number of induced and spontaneous
      abortions, live births and ectopic pregnancies reported by the NHS and Office for
      National Statistics. Direct medical costs associated with these were obtained
      from the NHS Reference Costs. RESULTS: In 2010, there were an estimated 225,600
      unintended pregnancies in England, of which 218,100 were paid for by the NHS. Of
      these, 155,500 led to induced abortions, 53,900 to births, 7,500 to spontaneous
      abortions and 1,200 to ectopic pregnancies. These unintended pregnancies cost the
      NHS L193,200,000 ($299,200,000) in direct medical costs. DISCUSSION: London, the
      North West and the West Midlands should be targeted in efforts to reduce
      unintended pregnancies. More specifically, women between the ages of 20 and 34
      years produce the greatest costs.

PMID- 22878146
TI  - NHE1 inhibition improves tissue perfusion and resuscitation outcome after severe
      hemorrhage.
AB  - INTRODUCTION: This study tested the hypothesis that blockade of the pH-regulatory
      protein, Na+/H+ exchanger (NHE1) during prolonged hemorrhagic shock can protect
      against whole-body ischemia-reperfusion injury, resulting in improved
      neurological outcomes. METHODS: We used a total of 24 male pigs in this study. We
      excluded two animals: one because of cardiac arrest after the initial hemorrhage,
      and the second because of a catheter malfunction for color microspheres. In
      Series 1, anesthetized pigs underwent an initial hemorrhage of 40 mL/kg for 30
      min, and then were given either 3 mg/kg of NHE1 selective inhibitor BIIB513 (n =
      6) or vehicle (n = 6). At 1 h after treatment, all animals received fluid
      resuscitation. We assessed survival and neurologic outcomes 72 h
      postresuscitation. In Series 2, we measured organ blood flow in a separate group
      of control (n = 5) and BIIB513-treated pigs (n = 5) undergoing the same
      experimental paradigm. RESULTS: Five of six control animals failed to be weaned
      from mechanical ventilation. We killed another control animal the next day
      because of severe complications. In contrast, all six animals treated with
      BIIB513 were weaned off the ventilator, and all but one survived the 72-h
      experimental period with normal neurological outcome. Results showed that NHE1
      inhibition with BIIB513 improved blood flow to the brain, heart, and kidney, and
      prevented the development of metabolic acidosis in the 1-h hypovolemic period. In
      addition, BIIB513 facilitated the hemodynamic response to fluid resuscitation,
      increased mixed venous blood oxygen saturation and oxygen delivery, and reduced
      proinflammatory cytokine release and multiorgan injury compared with vehicle
      controls. CONCLUSIONS: In this study, NHE1 inhibition with BIIB513 improved vital
      organ blood flow, prevented the development of metabolic acidosis during
      prolonged hypovolemia, and facilitated the hemodynamic response to fluid
      resuscitation, resulting in increased survival and normal neurological outcomes.

PMID- 22878147
TI  - Preserving hepatic artery flow during portal triad blood inflow occlusion
      improves remnant liver regeneration in rats after partial hepatectomy.
AB  - BACKGROUND: In the present study, we compared preservation of the hepatic artery
      flow during liver blood inflow occlusion with total portal triad blood flow
      clamping (the Pringle maneuver) to examine their effects on liver regeneration in
      rats after partial hepatectomy. MATERIALS AND METHODS: Male Wistar rats were
      randomized to a control group (without hepatic inflow occlusion), an occlusion of
      the portal triad (OPT) group (OPT for 30 min under portal blood bypass), and an
      occlusion of the portal vein (OPV) group (OPV only for 30 min under portal blood
      bypass). All the rats underwent partial hepatectomy at the end of hepatic blood
      control. Liver regeneration was assessed on days 3 and 7 after hepatectomy. Liver
      damage, extracellular signal-regulated kinase-1/2 activation, and cytokine
      expression of the remnant liver in the first 24 h after hepatectomy were also
      assessed. RESULTS: Significantly greater liver regeneration, at a level similar
      to that of the control group, as indicated by the percentage of the initial liver
      weight, proliferating cell nuclear antigen and Ki-67 labeling indexes, and
      technetium-99m galactosyl human serum albumin liver uptake, was observed in the
      OPV group on day 3 after hepatectomy (P < 0.05 versus the OPT group). Liver
      damage, as represented by alanine aminotransferase and aspartate aminotransferase
      measurement and histopathologic examination, was substantially alleviated in the
      OPV group compared with the OPT group. In contrast to the control and OPV groups,
      the OPT group had markedly increased extracellular signal-regulated kinase-1/2
      activation, heat shock protein 70, and interleukin-6 expression in response to
      ischemia and partial hepatectomy. CONCLUSIONS: Our results have indicated that
      compared with the Pringle maneuver, clamping the portal vein while preserving the
      hepatic artery flow during partial hepatectomy is better for remnant liver
      regeneration at an early posthepatectomy stage.

PMID- 22878148
TI  - Get on your boots: preparing fourth-year medical students for a career in
      surgery, using a focused curriculum to teach the competency of professionalism.
AB  - INTRODUCTION: Few educational programs exist for medical students that address
      professionalism in surgery, even though this core competency is required for
      graduate medical education and maintenance of board certification. Lapses in
      professional behavior occur commonly in surgical disciplines, with a negative
      effect on the operative team and patient care. Therefore, education regarding
      professionalism should begin early in the surgeon's formative process, to improve
      behavior. The goal of this project was to enhance the attitudes and knowledge of
      medical students regarding professionalism, to help them understand the role of
      professionalism in a surgical practice. METHODS: We implemented a 4-h seminar,
      spread out as 1-h sessions over the course of their month-long rotation, for 4th
      year medical students serving as acting interns (AIs) in General Surgery, a
      surgical subspecialty, Obstetrics/Gynecology, or Anesthesia. Teaching methods
      included lecture, small group discussion, case studies, and journal club. Topics
      included Cognitive/Ethical Basis of Professionalism, Behavioral/Social Components
      of Professionalism, Managing Yourself, and Leading While You Work. We assessed
      attitudes about professionalism with a pre-course survey and tracked effect on
      learning and behavior with a post-course questionnaire. We asked AIs to rate the
      egregiousness of 30 scenarios involving potential lapses in professionalism.
      RESULTS: A total of 104 AIs (mean age, 26.5 y; male to female ratio, 1.6:1)
      participated in our course on professionalism in surgery. Up to 17.8% of the AIs
      had an alternate career before coming to medical school. Distribution of intended
      careers was: General Surgery, 27.4%; surgical subspecialties, 46.6%;
      Obstetrics/Gynecology, 13.7%; and Anesthesia, 12.3%. Acting interns ranked
      professionalism as the third most important of the six core competencies, after
      clinical skills and medical knowledge, but only slightly ahead of communication.
      Most AIs believed that professionalism could be taught and learned, and that the
      largest obstacle was not enough time in the curriculum. The most effective
      reported teaching methods were mentoring and modeling; lecture and journal club
      were the effective. Regarding attitudes toward professionalism, the most
      egregious examples of misconduct were substance abuse, illegal billing, boundary
      issues, sexual harassment, and lying about patient data, whereas the least
      egregious examples were receiving textbooks or honoraria from drug companies,
      advertising, self-prescribing for family members, and exceeding work-hour
      restrictions. The most important attributes of the professional were integrity
      and honesty, whereas the least valued were autonomy and altruism. The AIs
      reported that the course significantly improved their ability to define
      professionalism, identify attributes of the professional, understand the
      importance of professionalism, and integrate these concepts into practice (all P
      < 0.01). CONCLUSIONS: Although medical students interested in surgery may already
      have well-formed attitudes and sophisticated knowledge about professionalism,
      this core competency can still be taught to and learned by trainees pursuing a
      surgical career.

PMID- 22878149
TI  - Ischemic postconditioning downregulates Egr-1 expression and attenuates
      postischemic pulmonary inflammatory cytokine release and tissue injury in rats.
AB  - BACKGROUND: The early growth response-1 (Egr-1) gene is upregulated after an
      ischemia-reperfusion (IR) challenge and upregulates target genes, such as
      proinflammatory cytokines. Ischemic postconditioning (IPostC) attenuates lung IR
      injury and reduces the systemic inflammatory response by activating heme
      oxygenase-1 (HO-1). However, the role of Egr-1 in IPostC protection against lung
      IR injury and inflammation and its interplay with HO-1 in IPostC protection is
      unknown. MATERIALS AND METHODS: Sprague-Dawley rats or cultured A549 cells were
      subjected to IR or hypoxia/reoxygenation with or without IPostC or hypoxic
      postconditioning in the presence or absence of Egr-1 inhibition using Egr-1
      antisense oligodeoxyrinonucleotide or Egr-1 small interfering RNA transfection.
      Lung injury was assessed by measuring the lung wet/dry weight ratio, histologic
      change, and malondialdehyde content. The amount of lactate dehydrogenase release
      in culture medium was detected to evaluate cell injury. The protein expression of
      Egr-1, interleukin (IL)-1beta, and HO-1 was assessed by Western blot. RESULTS:
      Inhibition of Egr-1 significantly attenuated lung IR injury and the inflammation
      response caused by IR or hypoxia/reoxygenation, as shown by the alleviated lung
      pathologic changes, decreased pulmonary malondialdehyde content, wet/dry ratio,
      reduced release of the cytokines tumor necrosis factor-alpha, IL-6, and IL-8 in
      the bronchoalveolar lavage, and reduced Egr-1, IL-1beta, and HO-1 protein
      expression and HO-1 activity. IPostC or hypoxic postconditioning reduced the
      postischemic Egr-1 expression and conferred similar protection against lung IR
      injury as Egr-1 inhibition. CONCLUSIONS: Egr-1 plays an important role in
      regulating the HO-1 production induced by IR or hypoxia/reoxygenation. Thus,
      downregulation of Egr-1 expression might represent one of the major mechanisms
      whereby IPostC confers protection against pulmonary IR insult.

PMID- 22878150
TI  - Prognostic implications of human leukocyte antigen class I expression in patients
      who underwent surgical resection for non-small-cell lung cancer.
AB  - BACKGROUND: The purpose of the present study was to clarify the prognostic
      significance of human leukocyte antigen (HLA) class I expression in patients with
      non-small-cell lung cancer who underwent complete surgical resection. PATIENTS
      AND METHODS: The expression of HLA class I molecules was evaluated in 403
      resected NSCLC specimens using immunohistochemistry. The results were scored as
      the percentage of stained tumor cells and were categorized into three groups: 0%
      24% (decreased), 25%-79% (heterogeneous), and 80% or more (normal). RESULTS: The
      expression of HLA class I was evaluated in 124 tumors in the normal expression
      group, 181 tumors in the heterogeneous expression group, and 98 tumors in the
      decreased expression group. The 5-year survival rate of all patients after
      surgery according to the HLA class I expression in the normal, heterogeneous, and
      decreased groups was 76.6%, 65.9%, and 76.1%, respectively. The prognosis was
      significantly better in the normal expression group than in the heterogeneous
      group. Normal HLA class I expression also correlated with favorable survival in
      patients with stage I disease. CONCLUSIONS: The normal expression of HLA class I
      was associated with a favorable prognosis compared with the heterogeneous
      expression group, but no significant difference was observed between the normal
      expression and decreased expression groups.

PMID- 22878151
TI  - Outcomes after peripheral extracorporeal membrane oxygenation therapy for
      postcardiotomy cardiogenic shock: a single-center experience.
AB  - BACKGROUND: We assessed the short-term outcomes and predictors of 30-d mortality
      in patients requiring temporary, peripheral extracorporeal membrane oxygenation
      (ECMO) for postcardiotomy cardiac failure. METHODS: The data were retrospectively
      obtained using our institutional patient database. All patients who had received
      peripheral ECMO support after surgery for acquired heart disease from 2006 to
      2010 were included in the present study. The demographic and perioperative
      variables of the 30-d survivors and nonsurvivors were compared using the chi
      square and t-test, and multivariate logistic regression analysis was performed to
      identify the predictors of 30-d all-cause mortality. RESULTS: A total of 77
      patients with a mean age of 60 +/- 13 years were included in the present
      analysis. Successful weaning from peripheral ECMO was achieved in 62% after 79 +/
      57 h of ECMO support. The overall 30-d mortality rate was 70%, and mortality was
      reduced to 52% in the patients in whom ECMO support could be weaned successfully.
      Age (per year) at ECMO implantation was the only independent preoperative
      predictor of 30-d mortality (odds ratio 1.09, 95% confidence interval 1.03-1.15;
      P = 0.003). In addition, greater lactate levels after 24 h of ECMO therapy, a
      longer duration of ECMO support, and the presence of any ECMO-related or
      gastrointestinal complications were independent predictive factors for 30-d
      mortality (P < 0.05). CONCLUSIONS: ECMO therapy provides a valuable therapeutic
      strategy for postcardiotomy myocardial failure but is still limited by high
      complication rates with fewer than 30% of patients discharged from the hospital.
      Patient age appears to be an essential preoperative predictor for mortality, and
      the blood lactate level is a relevant marker for the assessment of efficient ECMO
      support.

PMID- 22878152
TI  - Establishing a disc degeneration model using computed tomography-guided
      percutaneous puncture technique in the rabbit.
AB  - BACKGROUND: Various animal models have been developed to investigate the complex
      mechanisms leading to intervertebral disc disorders and to evaluate the different
      therapeutic options. The needle puncture technique is commonly used to induce
      intervertebral degeneration in animal models. The present study aimed to
      establish a rabbit model of intervertebral disc degeneration using a simple,
      minimally invasive procedure. METHODS AND MATERIALS: The animal model was created
      in the rabbit using computed tomography-guided percutaneous puncture technology.
      An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth.
      Radiographic, histologic, and biochemical analyses and magnetic resonance imaging
      were performed to assess the consequent disc degeneration. RESULTS: Significant
      disc space narrowing was observed as early as 4 wk, and osteophytes were formed
      at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a
      progressive loss of T2-weighted signal intensity at the stabbed discs throughout
      the 12-wk period. The histologic analysis showed a progressive loss of the normal
      architecture from 4 wk to the end point. The biochemical assays suggested that
      the expression of proteoglycan decreased progressively with increasing time.
      CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration
      model was established successfully using computed tomography-guided percutaneous
      puncture technology in the rabbit. The puncture procedure can be performed with
      minimal damage and handling of the other structures, ensuring a uniform
      reproducible disc degeneration model.

PMID- 22878153
TI  - Mechanical loading, damping, and load-driven bone formation in mouse tibiae.
AB  - Mechanical loads play a pivotal role in the growth and maintenance of bone and
      joints. Although loading can activate anabolic genes and induce bone remodeling,
      damping is essential for preventing traumatic bone injury and fracture. In this
      study we investigated the damping capacity of bone, joint tissue, muscle, and
      skin using a mouse hindlimb model of enhanced loading in conjunction with finite
      element modeling to model bone curvature. Our hypothesis was that loads were
      primarily absorbed by the joints and muscle tissue, but that bone also
      contributed to damping through its compression and natural bending. To test this
      hypothesis, fresh mouse distal lower limb segments were cyclically loaded in
      axial compression in sequential bouts, with each subsequent bout having less
      surrounding tissue. A finite element model was generated to model effects of bone
      curvature in silico. Two damping-related parameters (phase shift angle and energy
      loss) were determined from the output of the loading experiments. Interestingly,
      the experimental results revealed that the knee joint contributed to the largest
      portion of the damping capacity of the limb, and bone itself accounted for
      approximately 38% of the total phase shift angle. Computational results showed
      that normal bone curvature enhanced the damping capacity of the bone by
      approximately 40%, and the damping effect grew at an accelerated pace as
      curvature was increased. Although structural curvature reduces critical loads for
      buckling in beam theory, evolution apparently favors maintaining curvature in the
      tibia. Histomorphometric analysis of the tibia revealed that in response to axial
      loading, bone formation was significantly enhanced in the regions that were
      predicted to receive a curvature-induced bending moment. These results suggest
      that in addition to bone's compressive damping capacity, surrounding tissues, as
      well as naturally-occurring bone curvature, also contribute to mechanical
      damping, which may ultimately affect bone remodeling and bone quality.

PMID- 22878155
TI  - Vitamin D deficiency in northern Vietnam: prevalence, risk factors and
      associations with bone mineral density.
AB  - PURPOSE: Vitamin D deficiency has been linked to osteoporosis and also to the
      risk of cancer, autoimmune disorders and cardiovascular diseases. This study
      sought to determine the prevalence of, and risk factors for, vitamin D deficiency
      and its relationship with bone mineral density (BMD) in a Vietnamese population.
      METHODS: This cross-sectional study involved 269 women and 222 men aged 13-83
      years, who were randomly selected from urban and rural areas in northern Vietnam.
      Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone
      (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency
      was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X
      ray absorptiometry. RESULTS: The prevalence of vitamin D deficiency in women was
      30%, almost two-fold higher than in men (16%). Significant predictors of vitamin
      D deficiency in women were urban residency (p<0.01) and age less than 30 years
      (p<0.01), whereas use of contraceptive pills was protective (p<0.01). In men,
      winter season was the only significant predictor of vitamin D deficiency
      (p<0.01). In multiple linear regression analysis, serum levels of 25(OH)D were
      positively associated with BMD in both women (p<0.001) and men (p<0.001).
      CONCLUSIONS: These data suggest that the prevalence of vitamin D deficiency is
      high in the Vietnamese population, and that part of this prevalence could be
      explained by low exposure to sunlight (urban residency and winter season). The
      high prevalence of vitamin D deficiency should raise the awareness of potentially
      important health issues such as osteoporosis within the Vietnamese society.

PMID- 22878154
TI  - Cortical microstructure and estimated bone strength in young amenorrheic
      athletes, eumenorrheic athletes and non-athletes.
AB  - CONTEXT: Lower bone density in young amenorrheic athletes (AA) compared to
      eumenorrheic athletes (EA) and non-athletes may increase fracture risk during a
      critical time of bone accrual. Finite element analysis (FEA) is a unique tool to
      estimate bone strength in vivo, and the contribution of cortical microstructure
      to bone strength in young athletes is not well understood. OBJECTIVE: We
      hypothesized that FEA-estimated stiffness and failure load are impaired in AA at
      the distal radius and tibia compared to EA and non-athletes despite weight
      bearing exercise. DESIGN AND SETTING: Cross-sectional study; Clinical Research
      Center SUBJECTS: 34 female endurance athletes involved in weight-bearing sports
      (17 AA, 17 EA) and 16 non-athletes (14-21 years) of comparable age, maturity and
      BMI OUTCOME MEASURES: We used HR-pQCT images to assess cortical microarchitecture
      and FEA to estimate bone stiffness and failure load. RESULTS: Cortical perimeter,
      porosity and trabecular area at the weight-bearing tibia were greater in both
      groups of athletes than non-athletes, whereas the ratio (%) of cortical to total
      area was lowest in AA. Despite greater cortical porosity in EA, estimated tibial
      stiffness and failure load was higher than in non-athletes. However, this
      advantage was lost in AA. At the non-weight-bearing radius, failure load and
      stiffness were lower in AA than non-athletes. After controlling for lean mass and
      menarchal age, athletic status accounted for 5-9% of the variability in stiffness
      and failure load, menarchal age for 8-23%, and lean mass for 12-37%. CONCLUSION:
      AA have lower FEA-estimated bone strength at the distal radius than non-athletes,
      and lose the advantage of weight-bearing exercise seen in EA at the distal tibia.

PMID- 22878156
TI  - The effect of alendronate doped calcium phosphates on bone cells activity.
AB  - This study demonstrates that octacalcium phosphate (OCP) is a suitable substrate
      for alendronate local action towards bone cells. The results of the structural,
      spectroscopic, and microscopic investigation show that soaking OCP into
      alendronate solutions provoked the deposition of long crystalline rod-shaped
      formations, most likely a calcium alendronate complex, onto the calcium
      phosphate. The amount of alendronate loaded onto OCP increased as a function of
      the bisphosphonate concentration in solution. Osteoblast and osteoclast response
      was tested in single and in co-cultures on OCP containing 6.4 wt.% AL (OCP-AL),
      and for comparison on hydroxyapatite (HA) containing a similar amount (5.9 wt.%)
      of AL (HA-AL), as well as on pure OCP and HA as reference materials. Alendronate
      loaded materials displayed a beneficial effect on osteoblast activity and
      differentiation, whereas they inhibited osteoclast proliferation and
      differentiation. Crosstalking between osteoblast-like MG63 cells and human
      osteoclasts enhanced their response to alendronate. Moreover, OCP displayed a
      greater stimulating effect than HA on osteoblast differentiation, and AL
      promotion of osteoblast differentiation and mineralization was enhanced in OCP-AL
      with respect to HA-AL.

PMID- 22878157
TI  - Impact of margin status on outcomes following accelerated partial breast
      irradiation using single-lumen balloon-based brachytherapy.
AB  - PURPOSE: To examine the impact of margin status on clinical outcomes for patients
      enrolled in the American Society of Breast Surgeons (ASBrS) MammoSite((r))
      Registry Trial. METHODS AND MATERIALS: One thousand four hundred forty-nine cases
      of early-stage breast cancer underwent breast-conserving therapy with a single
      lumen balloon-based applicator used to deliver adjuvant accelerated partial
      breast irradiation (34Gy in 10, bid fractions). One thousand two hundred fifty
      five cases (87%) had invasive breast cancer (median size=10mm) and 194 cases
      (13%) had ductal carcinoma in situ (DCIS; median size=8mm). RESULTS: Patients
      were stratified by margin status into negative (n=1326), close (<2mm; n=110), and
      positive (n=13) margins. One hundred twenty-three cases (8.5%) had close or
      positive margins. Overall, no statistical difference in the 6-year rate of
      ipsilateral breast tumor recurrence (IBTR) was noted for close margins compared
      with that of margin-negative patients (8.7% vs. 4.1%, p=0.10) or for positive
      margins compared with that of margin-negative patients (14.3% vs. 4.1%, p=0.41).
      In patients with DCIS, there was a statistically significant increase in IBTR
      with close margins (17.6% vs. 4.2%, p=0.004) and when close and positive margins
      were pooled (15.7% vs. 4.2%, p=0.01 with a nonsignificant reduction in disease
      free survival for DCIS patients with close margins (82.4% vs. 90.8%, p=0.12). The
      increase in IBTR for close and close/positive patients was secondary to
      statistically significant increases in elsewhere failures rather than true
      recurrences/marginal misses. CONCLUSION: Nonsignificant increases in the rates of
      IBTR were noted with close and positive margins for invasive cancer with further
      data required to validate these findings.

PMID- 22878158
TI  - Transcriptional changes of antioxidant responses, hormone signalling and
      developmental processes evoked by the Brassica napus SHOOTMERISTEMLESS during in
      vitro embryogenesis.
AB  - Previous work showed that alterations in Brassica napus (Bn) SHOOTMERISTEMLESS
      (BnSTM) expression levels influence microspore-derived embryogenesis in B. napus.
      While over-expression of BnSTM increased microspore-derived embryo (MDE) yield
      and quality, down-regulation of BnSTM repressed embryo formation [16].
      Transcriptional analyses were conducted to investigate the molecular mechanisms
      underpinning these responses. The induction of BnSTM resulted in a heavy
      transcriptional activation of genes involved in antioxidant responses, hormone
      signalling and developmental processes. Several antioxidant enzymes, including
      catalases, superoxide dismutases, and components of the Halliwell-Asada cycle
      were induced in embryos ectopically expressing BnSTM and contributed to the
      removal of reactive oxygen species (ROS). These changes were accompanied by
      elevated levels of ascorbate and glutathione, which have been shown to promote
      embryonic growth and development. Induction or repression of BnSTM altered the
      early cytokinin response, whereas late responses, modulated by Type-A Arabidopsis
      response regulators (ARRs), were induced in MDEs over-expressing BnSTM. Major
      differences between transgenic MDEs were also observed in the expression pattern
      of several auxin transporters and key developmental factors required for normal
      embryogenesis. While some of these factors, BABYBOOM1 (BBM1) and SOMATIC
      EMBRYOGENESIS RECEPTOR KINASE (SERK), play a key role during early embryogeny,
      others, CYP78A5, LEAFY COTYLEDON1 and 2 (LEC1 and LEC2), as well as WOX2 and 9,
      are required for proper embryo development. Collectively these results
      demonstrate the involvement of BnSTM in novel developmental processes which can
      be utilized to enhance in vitro embryogenesis.

PMID- 22878159
TI  - Acute puerperal inversion of uterus: a simplified and effective method of
      hydrostatic replacement.

PMID- 22878160
TI  - Production of wax esters in plant seed oils by oleosomal cotargeting of
      biosynthetic enzymes.
AB  - Wax esters are neutral lipids exhibiting desirable properties for lubrication.
      Natural sources have traditionally been whales. Additionally some plants produce
      wax esters in their seed oil. Currently there is no biological source available
      for long chain length monounsaturated wax esters that are most suited for
      industrial applications. This study aimed to identify enzymatic requirements
      enabling their production in oilseed plants. Wax esters are generated by the
      action of fatty acyl-CoA reductase (FAR), generating fatty alcohols and wax
      synthases (WS) that esterify fatty alcohols and acyl-CoAs to wax esters. Based on
      their substrate preference, a FAR and a WS from Mus musculus were selected for
      this study (MmFAR1 and MmWS). MmWS resides in the endoplasmic reticulum (ER),
      whereas MmFAR1 associates with peroxisomes. The elimination of a targeting signal
      and the fusion to an oil body protein yielded variants of MmFAR1 and MmWS that
      were cotargeted and enabled wax ester production when coexpressed in yeast or
      Arabidopsis. In the fae1 fad2 double mutant, rich in oleate, the cotargeted
      variants of MmFAR1 and MmWS enabled formation of wax esters containing >65% oleyl
      oleate. The data suggest that cotargeting of unusual biosynthetic enzymes can
      result in functional interplay of heterologous partners in transgenic plants.

PMID- 22878162
TI  - Intracellular signaling in neurons: unraveling specificity, compensatory
      mechanisms and essential gene function.
AB  - Understanding how unique signaling outputs are generated in neurons using a
      limited set of intracellular signaling mechanisms has been a challenge. A
      combination of genetics and cell imaging, with tools developed to measure
      signaling outputs, has shown that the restricted presence of a signaling
      attenuator visibly alters the axonal range of the output and can be correlated
      with different behavioral outputs. Another question of interest is regarding the
      extent of genetic plasticity possible in the context of a single behavioral
      change. Recent molecular and genetic studies support the presence of parallel
      pathways that can compensate for the primary defect both at the level of
      physiology and behavior.

PMID- 22878161
TI  - Candidate and non-candidate genes in behavior genetics.
AB  - In this review we discuss recent developments in psychiatric genetics: on the one
      hand, studies using whole genome approaches (genome-wide association studies
      (GWAS) and exome sequencing) are coming close to finding genes and molecular
      variants that contribute to disease susceptibility; on the other candidate genes,
      such as the serotonin transporter, continue to dominate in genetic studies of
      brain imaging phenotypes and in protracted searches for gene by environment
      interactions. These two areas intersect, in that new information about genetic
      effects from whole genome approaches, should (but does not always) inform the
      single locus analyses.

PMID- 22878163
TI  - Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to
      lower episodic memory performance in clinically normal older individuals.
AB  - The objective of this study was to evaluate the relationship of amyloid burden,
      as assessed by florbetapir F 18 ((18)F-AV-45) amyloid positron emission
      tomography, and cognition in healthy older control (HC) subjects. Seventy-eight
      HC subjects were assessed with a brief cognitive test battery and positron
      emission tomography (PET) imaging with (18)F-AV-45. A standard uptake value ratio
      was computed for mean data from 6 cortical regions using a whole cerebellum
      reference region. Scans were also visually rated as amyloid positive or amyloid
      negative by 3 readers. Higher standard uptake value ratio correlated with lower
      immediate memory (r = -0.33; p = 0.003) and delayed recall scores (r = -0.25; p =
      0.027). Performance on immediate recall was also lower in the visually rated
      amyloid positive compared with amyloid negative HC (p = 0.04), with a similar
      trend observed in delayed recall (p = 0.06). These findings support the
      hypothesis that higher amyloid burden is associated with lower memory performance
      among clinically normal older subjects. Longitudinal follow-up is ongoing to
      determine whether (18)F-AV-45 may also predict subsequent cognitive decline.

PMID- 22878164
TI  - VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient.
AB  - Previously, we have reported amyotrophic lateral sclerosis (ALS) families with
      multiple mutations in major ALS-associated genes. These findings provided
      evidence for an oligogenic basis of ALS. In our present study, we screened a
      cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and
      765 control subjects of Dutch descent for mutations in vesicle-associated
      membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in
      a familial ALS patient known to have a chromosome 9 open reading frame 72
      (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects,
      located in a region with high evolutionary conservation, and predicted to have
      damaging effects. Taken together, these findings provide additional evidence for
      an oligogenic basis of ALS.

PMID- 22878165
TI  - Effect of age on neocortical brain cells in 90+ year old human females--a cell
      counting study.
AB  - An increasing number of people are living past the age of 100 years, but little
      is known about what differentiates centenarians from the rest of the population.
      In this study, brains from female subjects in 3 different age groups, 65-75 years
      (n = 8), 76-85 years (n = 8), and 94-105 years (n = 7), were examined to estimate
      the total number of neocortical neurons, astrocytes, oligodendrocytes, and
      microglia. There was no statistically significant difference in the mean number
      of neocortical neurons between the 3 groups: 17.9 * 10(9) (CV = SD/mean = 0.15)
      in the youngest group, 18.1 * 10(9) (CV = 0.22) in the second group, and 16.32 *
      10(9) (CV = 0.24) in the oldest group. However, there was a significant
      difference in the total number of neocortical glial cells between the youngest
      (41.0 * 10(9)) and oldest (29.0 * 10(9)) age groups (p = 0.013). The significance
      was probably driven by a significant difference in the total number of
      neocortical oligodendrocytes that differed significantly between the youngest
      (27.5 * 10(9)) and oldest (18.1. * 10(9), p = 0.006) age groups. In conclusion,
      very old individuals have brain neuron numbers comparable with younger
      individuals, which may be encouraging for those who live into the "fourth age"
      and may contribute to the longevity of this exceptional group of people.

PMID- 22878166
TI  - Sirolimus-eluting stents for treatment of infrapopliteal arteries reduce clinical
      event rate compared to bare-metal stents: long-term results from a randomized
      trial.
AB  - OBJECTIVES: The study investigated the long-term clinical impact of sirolimus
      eluting stents (SES) in comparison with bare-metal stents (BMS) in treatment of
      focal infrapopliteal lesions. BACKGROUND: There is evidence that SES reduce the
      risk of restenosis after percutaneous infrapopliteal artery revascularization. No
      data from randomized trials are available concerning the clinical impact of this
      finding during long-term follow-up. METHODS: The study extended the follow-up
      period of a prospective, randomized, multicenter, double-blind trial comparing
      polymer-free SES with placebo-coated BMS in the treatment of focal infrapopliteal
      de novo lesions. The main study endpoint was the event-free survival rate defined
      as freedom from target limb amputation, target vessel revascularization,
      myocardial infarction, and death. Secondary endpoints include amputation rates,
      target vessel revascularization, and changes in Rutherford-Becker class. RESULTS:
      The trial included 161 patients. The mean target lesion length was 31 +/- 9 mm.
      Thirty-five (23.3%) patients died during a mean follow-up period of 1,016 +/- 132
      days. The event-free survival rate was 65.8% in the SES group and 44.6% in the
      BMS group (log-rank p = 0.02). Amputation rates were 2.6% and 12.2% (p = 0.03),
      and target vessel revascularization rates were 9.2% and 20% (p = 0.06),
      respectively. The median (interquartile range) improvement in Rutherford-Becker
      class was -2 (-3 to -1) in the SES group and -1 (-2 to 0) in the BMS group,
      respectively (p = 0.006). CONCLUSIONS: Long-term event-free survival, amputation
      rates, and changes in Rutherford-Becker class after treatment of focal
      infrapopliteal lesions are significantly improved with SES in comparison with
      BMS. (YUKON-Drug-Eluting Stent Below the Knee-Randomised Double-Blind Study
      [YUKON-BTX]; NCT00664963).

PMID- 22878167
TI  - Intra-atrial mass-thrombus versus myxoma, post-amplatzer atrial septal defect
      closure device deployment.

PMID- 22878169
TI  - The accuracy of cardiovascular computed tomography in the presence of a high
      coronary calcium score may be underestimated.

PMID- 22878170
TI  - Poorly compressible leg arteries: a specific presentation of peripheral artery
      disease.

PMID- 22878172
TI  - Optical frequency domain imaging to reveal an angiographically inapparent very
      late stent thrombosis as the cause of an acute coronary syndrome.

PMID- 22878173
TI  - Nasal carriage rate and molecular epidemiology of methicillin-resistant
      Staphylococcus aureus among medical students at a Taiwanese university.
AB  - OBJECTIVE: To investigate whether clinical exposure in the hospital affects nasal
      carriage of methicillin-resistant Staphylococcus aureus (MRSA) among medical
      students. METHODS: A total of 322 medical students, both pre-clinical (n=167) and
      clinical (n=155), were recruited. Specimens were obtained from the nares of the
      subjects for the detection of S. aureus. A questionnaire was completed for each
      subject. All the MRSA isolates were further molecularly characterized. RESULTS:
      The overall S. aureus carriage rate was 19.3%, with a rate of 16.8% for pre
      clinical students and 21.9% for clinical students (p=0.26). The carriage rate of
      MRSA was 2.2%, with a rate of 2.4% for pre-clinical students and 1.9% for
      clinical students (p=0.54). There was no significant difference between the pre
      clinical and clinical students in terms of nasal carriage of S. aureus and MRSA.
      All seven MRSA isolates were categorized as community strains in Taiwan. The risk
      factors for acquisition of S. aureus included male gender, age >=23 years, and
      not taking antibiotics in the past year. CONCLUSIONS: As in the general
      population, less than 5% of medical students in northern Taiwan harbored MRSA,
      categorized as community strains, in their nares. The carriage of MRSA was not
      affected by clinical exposure in the hospital for 1-2 years.

PMID- 22878174
TI  - Event history analysis of dengue fever epidemic and inter-epidemic spells in
      Barbados, Brazil, and Thailand.
AB  - OBJECTIVE: This study investigated meteorological and demographic factors
      affecting the length of dengue fever epidemics and the length of time between
      epidemics in Barbados, Brazil, and Thailand. METHODS: Region-specific
      meteorological and demographic data were collected for 104 sites from public
      sources. Fixed effects piecewise logistic event history analysis was used to
      quantify the effects of time-varying covariates on the duration of inter-epidemic
      spells and for the duration of epidemics. RESULTS: Mean monthly temperature was
      the most important factor affecting the duration of both inter-epidemic spells
      (beta=0.543; confidence interval (CI) 0.4954, 0.5906) and epidemic spells (beta=
      0.648; CI -0.7553, -0.5405). Drought conditions increased the time between
      epidemics. Increased temperature hastened the onset of an epidemic, and during an
      epidemic, higher mean temperature increased the duration of the epidemic.
      CONCLUSIONS: By using a duration analysis, this study offers a novel approach for
      investigating the dynamics of dengue fever epidemiology. Furthermore, these
      results offer new insights into prior findings of a correlation between
      temperature and the geographic range and vector efficiency of dengue fever.

PMID- 22878175
TI  - Systemic shRNA mediated knock down of S100A4 in colorectal cancer xenografted
      mice reduces metastasis formation.
AB  - The metastasis-inducing protein S100A4 was found to be a prognostic indicator for
      the development of metachronous metastases. S100A4 expression levels correlate
      with the formation of human colorectal cancer metastases and shorter patients'
      survival. Inhibition of S100A4 expression in patients might therefore result in
      decreased metastasis formation and prolonged survival. In the present study, we
      used shRNA expression plasmids to inhibit S100A4 expression in the colorectal
      cancer cell lines HCT116, SW620 and DLD-1. Cell lines with reduced S100A4
      expression showed reduced cell migration and invasion in vitro. The knock-down of
      S100A4 expression also led to significantly diminished formation of liver
      metastases when intrasplenically transplanted in mice (P = 0.004). We then
      focused on the therapeutic potential of systemically applied shRNA expression
      plasmids acting on S100A4 via repeated hydrodynamics-based tail vein injection of
      plasmid DNA. Mice, intrasplenically transplanted with HCT116 cells and treated
      systemically with S100A4-shRNA plasmids, showed a decrease of S100A4 and MMP9
      expression levels, resulting in significantly reduced liver metastases (P =
      0.005). In summary, we show for the first time the intratumoral knock down of
      S100A4 via systemic application of S100A4-shRNA plasmid DNA, which restricts
      metastasis formation in a xenografted mouse model of colorectal cancer.

PMID- 22878176
TI  - Understanding inhibitory mechanisms of lumbar spinal manipulation using H-reflex
      and F-wave responses: a methodological approach.
AB  - The purpose of this research was to characterize unique neurophysiologic events
      following a high velocity, low amplitude (HVLA) spinal manipulation (SM)
      procedure. Descriptive time series analysis techniques of time plots, outlier
      detection and autocorrelation functions were applied to time series of tibial
      nerve H-reflexes that were evoked at 10-s intervals from 100 s before the event
      until 100 s after three distinct events L5-S1 HVLA SM, or a L5-S1 joint pre
      loading procedure, or the control condition. Sixty-six subjects were randomly
      assigned to three procedures, i.e., 22 time series per group. If the detection of
      outliers and correlograms revealed a pattern of non-randomness that was only time
      locked to a single, specific event in the normalized time series, then an
      experimental effect would be inferred beyond the inherent variability of H-reflex
      responses. Tibial nerve F-wave responses were included to determine if any new
      information about central nervous function following a HVLA SM procedure could be
      ascertained. Time series analyses of H(max)/M(max) ratios, pre-post L5-S1 HVLA
      SM, substantiated the hypothesis that the specific aspects of the manipulative
      thrust lead to a greater attenuation of the H(max)/M(max) ratio as compared to
      the non-specific aspects related to the postural perturbation and joint pre
      loading. The attenuation of the H(max)/M(max) ratio following the HVLA SM
      procedure was reliable and may hold promise as a translational tool to measure
      the consistency and accuracy of protocol implementation involving SM in clinical
      trials research. F-wave responses were not sensitive to mechanical perturbations
      of the lumbar spine.

PMID- 22878177
TI  - Empirical mode decomposition based detrended sample entropy in
      electroencephalography for Alzheimer's disease.
AB  - Quantitative electroencephalographs (qEEG) provide a potential method to
      objectively quantify the cortical activations in Alzheimer's disease (AD), but
      they are too insensitive to probe the alteration of EEG in the early AD. The
      sample entropy (SaEn) attempts to quantify the complex information embedded in
      EEG non-linearly, which fits in that EEG originates from non-linear interactions.
      However, a technical issue which has been ignored by most researchers is that the
      signal should be stationary. In order to resolve the non-stationarity of SaEn in
      EEG to improve the sensitivity, an empirical mode decomposition (EMD) was applied
      for detrending in this study. Twenty-seven AD patients (9M/18F; mean age 74.0+/
      1.5 years) were included. Their initial Minimal Mental Status Examination was
      19.3+/-0.7. They received the first resting-awake 30-mine EEG before the therapy.
      Five of them received a follow-up examination within 6 months after the therapy.
      The 30-s EEG data without artifacts were selected and analyzed with a new
      proposed method, "EMD-based detrended-SaEn" to attenuate the influence of
      intrinsic non-stationarity. The correlation factors in 27 AD patients showed a
      moderate correlation (0.361-0.523, p<0.05) between MMSE and EMD-based detrended
      SaEn in Fp1, Fp2, F4 and T3. There was a high correlation (Correlation
      coefficient=0.975, p<0.05) between the changes of MMSE and the changes of EMD
      based detrended-SaEn in F7 in 5 follow-up patients. The dynamic complexity of EEG
      fluctuations is degraded by pathological degeneration, and EMD-based detrended
      SaEn provides an objective, non-invasive and non-expensive tool for evaluating
      and following AD patients.

PMID- 22878178
TI  - Parametric coordinate-based meta-analysis: valid effect size meta-analysis of
      studies with differing statistical thresholds.
AB  - The aim of coordinate-based meta-analysis is to provide valid quantitative
      summaries of the literature, while taking into account the specificities of
      neuroimaging data. Neuroimaging findings are usually reported as coordinates of
      effects surviving multiple comparison correction through statistical
      thresholding. Different studies may use widely differing censoring thresholds,
      ranging from strict family-wise corrections to more lenient "uncorrected"p
      values. However, standard meta-analysis methods do not take into account these
      differences, as findings from studies with varying thresholds are treated as
      though they were equivalent. The present paper details a development in
      coordinate-based meta-analysis which addresses this limitation. Parametric
      coordinate-based meta-analysis (PCM) computes valid estimates from thresholded
      measurements, integrating significant findings with the information generated by
      subthreshold measurements to produce asymptotically unbiased meta-analytical
      summaries. The method is validated through simulated data, and demonstrated in a
      real data meta-analysis of structural differences in grey matter density in
      depression. PCM demonstrates a sensitivity that is comparable or superior to
      existing coordinate-based meta-analysis methods, and demonstrates high agreement
      between its estimates and those obtained from the meta-analysis of unthresholded
      manual volumetric measurements. PCM constitutes a powerful approach to meta
      analysis, able to generate valid and unbiased effect-size summaries of studies
      with different statistical thresholds, and also allowing the integration of whole
      brain and region-of-interest studies.

PMID- 22878179
TI  - Immunostimulatory activities of the sulfated polysaccharide ascophyllan from
      Ascophyllum nodosum in in vivo and in vitro systems.
AB  - Splenic natural killer (NK) cell activity against YAC-1 cells increased in mice
      intraperitoneally injected with ascophyllan. Ascophyllan enhanced the
      cytotoxicity of RAW264.7 cells toward YAC-1 cells in a concentration-dependent
      manner. The cytotoxicity of ascophyllan-stimulated RAW264.7 cells as to YAC-1
      cells was suppressed with N(G)-nitro-L-arginine methyl ester hydrochloride (L
      NAME), an inhibitor of nitric oxide (NO) synthase, suggesting the involvement of
      NO in the cytotoxicity of ascophyllan-stimulated RAW264.7 cells.

PMID- 22878180
TI  - Effects of exogenous proline and glycinebetaine on the salt tolerance of rice
      cultivars.
AB  - Salinity significantly increased trisodium-8-hydroxy-1,3,6-pyrenetrisulphonic
      acid (PTS) uptake and decreased the K(+)/Na(+) ratio in salt-sensitive rice
      (Nipponbare) but did not markedly in salt-tolerant rice (Pokkali). Proline and
      glycinebetaine (betaine) suppressed the increase in PTS uptake and the decrease
      in the K(+)/Na(+) ratio in Nipponbare, but did not affect PTS uptake or the
      K(+)/Na(+) ratio in Pokkali.

PMID- 22878181
TI  - Transitional reactive oxygen species (ROS) production in fertilized egg embryos
      of devil stinger (Inimicus japonicus), a marine fish species.
AB  - A time-course analysis of reactive oxygen species (ROS) generation in fertilized
      eggs of the devil stinger (Inimicus japonicus) from 0 h post-fertilization (hpf)
      to the early larval stage indicated that the ROS level was highest in the 22 hpf
      embryo, and declined thereafter. Phorbol myristate acetate (PMA) had no effect on
      ROS generation by the 22 hpf embryo, whereas PMA significantly increased larval
      ROS generation, suggesting that the ROS generation mechanisms of the 22 hpf
      embryo and larva are different at least in terms of PMA-responsiveness. Our
      results suggest the presence of a specific ROS generation system in devil stinger
      embryo which can be transitionally activated during embryogenesis.

PMID- 22878182
TI  - Optimization of protease extraction from horse mango (Mangifera foetida Lour)
      kernels by a response surface methodology.
AB  - Protease is one of the most important industrial enzymes with a multitude of
      applications in both food and non-food sectors. Although most commercial
      proteases are microbial proteases, the potential of non-conventional protease
      sources, especially plants, should not be overlooked. In this study, horse mango
      (Mangifera foetida Lour) fruit, known to produce latex with a blistering effect
      upon contact with human skin, was chosen as a source of protease, and the effect
      of the extraction process on its protease activity evaluated. The crude enzyme
      was extracted from the kernels and extraction was optimized by a response surface
      methodology (RSM) using a central composite rotatable design (CCRD). The
      variables studied were pH (x(1)), CaCl(2) (x(2)), Triton X-100 (x(3)), and 1,4
      dithryeitol (x(4)). The results obtained indicate that the quadratic model is
      significant for all the variables tested. Based on the RSM model generated,
      optimal extraction conditions were obtained at pH 6.0, 8.16 mM CaCl(2), 5.0%
      Triton X-100, and 10.0 mM DTT, and the estimated response was 95.5% (w/w).
      Verification test results showed that the difference between the calculated and
      the experimental protease activity value was only 2%. Based on the t-value, the
      effects of the variables arranged in ascending order of strength were CaCl(2) <
      pH < DTT < Triton X-100.

PMID- 22878183
TI  - Violaceols function as actin inhibitors inducing cell shape elongation in
      fibroblast cells.
AB  - Violaceol-I and -II were isolated from a fractionated library of marine-derived
      fungal metabolites. These compounds increased the calcium ion concentration
      inside the cell and caused F-actin aggregation in rat fibroblast 3Y1 cells within
      3 h resulting in cell shape elongation. Calcium chelator BAPTA-AM (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester)
      inhibited violaceol-I and -II induced F-actin aggregation in 3Y1 cells, and hence
      violaceol-I and -II act in a calcium dependent manner. Violaceol-I and -II
      inhibited G-actin polymerization in vitro in a dose-dependent manner and strongly
      associated with G-actin, at dissociation equilibrium constants of 1.44 * 10(-8) M
      and 2.52 * 10(-9) M respectively. Here we report the identification of a novel
      function of violaceol-I and -II as actin inhibitors. Violaceol-I and -II induced
      cell shape elongation through F-actin aggregation in 3Y1 fibroblasts. These
      compounds may give researchers new insights into the role of actin in
      tumorigenesis and lead to the development of additional anti-tumor drugs.

PMID- 22878184
TI  - Accelerating effect of soy peptides containing collagen peptides on type I and
      III collagen levels in rat skin.
AB  - Two weeks of feeding soy peptides containing 2% collagen peptides increased the
      levels of type I and III tropocollagen and their mRNAs. In contrast, the diet did
      not increase the mRNA levels of rat hyaluronan synthases, serine
      palmitoyltransferase (the rate-limiting enzyme of ceramide synthesis), and 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the key enzyme of
      cholesterol synthesis). These results suggest that feeding of soy peptides with
      collagen peptides specifically enhanced the tropocollagen level in the skin.

PMID- 22878185
TI  - Dieckol isolated from Ecklonia cava protects against high-glucose induced damage
      to rat insulinoma cells by reducing oxidative stress and apoptosis.
AB  - Pancreatic beta cells are very sensitive to oxidative stress and this might play
      an important role in beta cell death with diabetes. The protective effect of
      dieckol, one of the phlorotannin polyphenol compounds purified from Ecklonia cava
      (E. cava), against high glucose-induced oxidative stress was investigated by
      using rat insulinoma cells. A high-glucose (30 mM) treatment induced the death of
      rat insulinoma cells, but dieckol, at a concentration 17.5 or 70 uM,
      significantly inhibited the high-glucose induced glucotoxicity. Treatment with
      dieckol also dose-dependently reduced thiobarbituric acid reactive substances
      (TBARS), the generation of intracellular reactive oxygen species (ROS), and the
      nitric oxide level increased by a high glucose concentration. In addition, the
      dieckol treatment increased the activities of antioxidative enzymes including
      catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in
      high glucose-pretreated rat insulinoma cells. Dieckol protected rat insulinoma
      cells damage under high glucose conditions. These effects were mediated by
      suppressing apoptosis and were associated with increased anti-apoptotic Bcl-2
      expression, and reduced pro-apoptotic cleaved caspase-3 expression. These
      findings indicate that dieckol might be useful as a potential pharmaceutical
      agent to protect against the glucotoxicity caused by hyperglycemia-induced
      oxidative stress associated with diabetes.

PMID- 22878186
TI  - Algicidal activity of marine Alteromonas sp. KNS-16 and isolation of active
      compounds.
AB  - The KNS-16 algicidal strain was isolated from a harmful alga bloom (HAB) area and
      identified as Alteromonas sp. based on 16S rDNA sequencing. The KNS-16 strain was
      found to control HABs by producing algicidal compounds in an indirect
      interaction. Four active compounds were isolated from KNS-16 culture, and their
      structures were analyzed by interpreting nuclear magnetic resonance and mass
      spectroscopy data. The structures were identified as 2-undecen-1'-yl-4-quinolone
      (1), 2-undecyl-4-quinolone (2), 3-hexyl-6-pentyl-4-hydroxyl-2H-pyran-2-one (3),
      and 6-heptyl-3-hexyl-4-hydroxyl-2H-pyran-2-one (4). Compound 1 was most active
      against HABs such as Heterosigma akashiwo, Cochlodinium polykrikoides, and
      Alexandrium tamarense with LC(50) values of 0.5-1.1 ug/mL. The four compounds
      exhibited high LC(50) values against aquaculture algae such as Tetaselmis
      suecica, Isochrysis galbana, and Pavlova lutheri at 39-66 ug/mL. Based on
      toxicity tests on the brine shrimp Artemia salina and the rotifer Brachionus
      rotundiformis, the four compounds showed ranges of 409-608 and 189-224 ug/mL of
      LC(50) for the two organisms, respectively. The LC(50) values for juvenile fish
      of Sebastes schlegelii were 284-304 ug/mL.

PMID- 22878187
TI  - Plasminogen activation by lactic acid bacteria.
AB  - Plasminogen was incubated with lactic acid bacteria and the plasmin activity in
      the mixture was measured. Three of 15 strains tested revealed significant
      plasminogen activation ability. Lactococcus lactis subsp. lactis biovar
      diacetylactis NIAI C59 showed the highest activity. The strain activated not only
      human plasminogen but also bovine plasminogen. The activity demonstrated a high
      level of thermal stability within a range of pH 3.0-9.0. The plasminogen
      activator activity in strain C59 increased after 15 h of cultivation, and reached
      a plateau after 21 h. A remarkable amount of activity was transferred to the
      solution when C59 cells were incubated in buffer solutions at pH 9.0 and above.

PMID- 22878188
TI  - Monoterpene alcohol metabolism: identification, purification, and
      characterization of two geraniol dehydrogenase isoenzymes from Polygonum minus
      leaves.
AB  - NADP(+)-dependent geraniol dehydrogenase (EC 1.1.1.183) is an enzyme that
      catalyzes the oxidation of geraniol to geranial. Stable, highly active cell-free
      extract was obtained from Polygonum minus leaves using polyvinylpolypyrrolidone,
      Amberlite XAD-4, glycerol, 2-mercaptoethanol, thiourea, and
      phenylmethylsulfonylfluoride in tricine-NaOH buffer (pH 7.5). The enzyme
      preparation was separated into two activity peaks, geraniol-DH I and II, by DEAE
      Toyopearl 650M column chromatography at pH 7.5. Both isoenzymes were purified to
      homogeneity in three chromatographic steps. The geraniol-DH isoenzymes were
      similar in molecular mass, optimal temperature, and pH, but the isoelectric
      point, substrate specificity, and kinetic parameters were different. The K(m)
      values for geraniol of geraniol-DH I and II appeared to be 0.4 mM and 0.185 mM
      respectively. P. minus geraniol-DHs are unusual among geraniol-DHs in view of
      their thermal stability and optimal temperatures, and also their high specificity
      for allylic alcohols and NADP(+).

PMID- 22878189
TI  - Contribution ratios of amyA, amyB, amyC genes to high-level alpha-amylase
      expression in Aspergillus oryzae.
AB  - Aspergillus oryzae strains express alpha-amylases abundantly, and the genome
      reference strain RIB40 has three alpha-amylase genes (amyA, amyB, and amyC).
      However, there is no information on the contribution ratios of individual alpha
      amylase genes to total expression. In this study, we generated single, double,
      and triple disruptants of alpha-amylase genes by employing a strain (DeltaligD)
      with high gene-targeting efficiency and pyrG marker recycling in A. oryzae. All
      the disruptants showed reduced activities of alpha-amylases, and the triple
      disruptant completely lost activity. Comparative analyses of the activities and
      mRNA amounts of the alpha-amylases suggest that the contribution of amyA to the
      alpha-amylase expression is smaller than those of amyB and amyC. The present
      study suggests that the ability to express a large amount of alpha-amylases in A.
      oryzae is attributed to gene duplication of genes such as amyB and amyC.

PMID- 22878190
TI  - Pilloin 5-O-beta-D-glucopyranoside from the stems of Diplomorpha ganpi.
AB  - The new flavonoid, pilloin 5-O-beta-D-glucopyranoside (1), was isolated from the
      stems of Diplomorpha ganpi (Family: Thymelaeaceae) together with 19 known
      compounds. The structures of these compounds were determined on the basis of
      spectroscopic data.

PMID- 22878191
TI  - Exploration of a possible partnership among orphan two-component system proteins
      in cyanobacterium Synechococcus elongatus PCC 7942.
AB  - To understand the induction of the adaptive response under various stress
      conditions, it is important to determine the partnership between histidine kinase
      and response regulators in the bacterial two-component system (TCS). The genes
      encoding TCS partners are usually comprised of an operon in the genome, but many
      of them are orphans in the cyanobacterial genome. There is little information on
      their partnerships in Synechococcus elongatus PCC 7942. Our comprehensive
      analysis of protein-protein interactions among all 37 full-length proteins and
      the truncated domains of 24 orphans revealed a number of specific interactions.
      They involved evolutionarily well-conserved orphan proteins among cyanobacterial
      species such as Synpcc7942_0453/Ycf29, NblS/RpaB, NblS/SrrA, SasA/RpaA, and
      SasA/Synpcc7942_2466. Our investigation of the transphosphorylation of
      interaction partners indicates that orphan TCSs comprise a complex signaling
      network.

PMID- 22878192
TI  - Mevalonate-dependent enzymatic synthesis of amorphadiene driven by an ATP
      regeneration system using polyphosphate kinase.
AB  - Polyphosphate kinase (PPK), which can regenerate ATP from ADP, was utilized in
      the mevalonate-dependent enzymatic synthesis of amorphadiene. The activity of
      PPK, cloned from Escherichia coli, was determined by (31)P-NMR. The yield from
      the PPK-catalyzed synthesis was 25%, 2.5 times higher than that without PPK. The
      (31)P-NMR analysis of the final reaction mixture indicated no accumulation of
      intermediates.

PMID- 22878193
TI  - Lack of the consensus sequence necessary for tryptophan prenylation in the ComX
      pheromone precursor.
AB  - ComX, an oligopeptide pheromone that stimulates the natural genetic competence
      controlled by quorum sensing in Bacillus subtilis and related bacilli, contains a
      prenyl-modified tryptophan residue. Since ComX is the only protein known to
      contain prenylated tryptophan, the universality of this unique posttranslational
      modification has yet to be determined. Recently, we developed a cell-free assay
      system in which the tryptophan residue in the ComX(RO-E-2) pheromone precursor
      derived from B. subtilis strain RO-E-2 can be geranylated by the ComQ(RO-E-2)
      enzyme. We report here our attempt to identify the consensus sequence surrounding
      the geranylated tryptophan residue by using the cell-free system with various
      ComX(RO-E-2) pheromone precursor analogs. We found that [47-58]ComX(RO-E-2),
      corresponding to the C-terminal 12-residue peptide of the pheromone precursor,
      contained a short sequence essential for geranylation. We also found that the
      length of the sequence between the tryptophan residue and the C-terminus was
      important for geranylation, and that some [47-58]ComX(RO-E-2) pheromone precursor
      amino acids were involved in the geranylation reaction. However, we could not
      identify a consensus sequence surrounding the geranylated tryptophan. Our
      evidence suggests that, like Rab which lacks a consensus sequence yet is
      geranylgeranyl-modified on a cysteine residue, the ComX pheromone and its
      precursor also lack a consensus sequence.

PMID- 22878194
TI  - Specific 5-hydroxylation of piperlongumine by Beauveria bassiana ATCC 7159.
AB  - A new hydroxylated derivative was efficiently prepared by transforming the
      natural anti-cancer product, piperlongumine, with Beauveria bassiana ATCC 7159.
      Its structure was determined to be 5-hydroxylpiperlongumine on the basis of the
      spectroscopic data. The absolute configuration at C-5 was established as R by
      Mosher's method.

PMID- 22878195
TI  - Consumption of Pueraria flower extract reduces body mass index via a decrease in
      the visceral fat area in obese humans.
AB  - In Japan, kudzu is a familiar plant, well-known as an ingredient in the Japanese
      style confections kudzu-kiri and kudzu-mochi. In this study, we focused on the
      flower of kudzu (Pueraria thomsonii) and conducted a clinical trial to
      investigate the effects of Pueraria thomsonii flower extract (PFE) on obesity
      using obese Japanese males and females (BMI >= 25 kg/m(2)). Eighty-one obese
      subjects were randomly divided into three groups and consumed test food
      containing 300 mg of PFE, 200 mg of PFE, and a placebo over 12 weeks. The results
      indicate that PFE intake reduces BMI and decreases, the visceral fat area, but
      not the subcutaneous fat area. In addition, the decrease in visceral fat area
      showed no sexual dimorphism. Consequently, we propose that PFE intake expresses
      its BMI reduction effects via a decrease in visceral fat area.

PMID- 22878196
TI  - Isolation of a new xanthylium-related pigment from adzuki beans Vigna angularis.
AB  - A new type of flavonoid was isolated from an adzuki bean-water extract by various
      chromatographic techniques. The chemical structure was determined by ultraviolet
      visible (UV-Vis) spectroscopy, mass spectrometry (MS), and various nuclear
      magnetic resonance (NMR) experiments, and it was found to be unique in that the
      xanthylium skeleton was present in this molecule.

PMID- 22878197
TI  - Cognitive enhancing effects of alpha asarone in amnesic mice by influencing
      cholinergic and antioxidant defense mechanisms.
AB  - The effect of alpha-asarone on impairment of cognitive performance caused by
      amnesic drug scopolamine was investigated. Treatment with alpha-asarone
      attenuated scopolamine-induced cognitive deficits as evaluated by passive
      avoidance and Y-maze test. Administration of alpha-asarone for 15 d improved
      memory and cognitive function as indicated by an increase in transfer latency
      time and spontaneous alternation in passive avoidance and the Y-maze test
      respectively. To understand the action of alpha-asarone, the levels of
      acetylcholinesterase (AChE), malondialdehyde (MDA), and superoxide dismutase
      (SOD) in the hippocampus (Hippo) and cerebral cortex (CC) of scopolamine-induced
      amnesic mice were evaluated. The mice treated with Scopolamine showed increased
      activity of AChE, MDA and SOD levels in both the Hippo and the CC area. Treatment
      with alpha-asarone attenuated the increased activity of AChE and normalized the
      MDA and SOD levels in the Hippo and the CC area in the scopolamine treated
      amnesic mice. These results suggest that alpha-asarone has a beneficial effect in
      cognitive impairment induced by dysfunction of cholinergic system in brain
      through inhibition of AChE activity and by influencing the antioxidant defense
      mechanism.

PMID- 22878198
TI  - Characterization of a chitosanase from Aspergillus fumigatus ATCC13073.
AB  - Chitosanase II was purified from the culture filtrate of Aspergillus fumigatus
      ATCC13073. The purified enzyme had a molecular mass of 23.5 kDa. The N-terminal
      amino acid sequence of chitosanase II was identical to those of other Aspergillus
      chitosanases belonging to glycoside hydrolase family 75. The optimum pH and
      temperature were pH 6.0 and 40  degrees C. Chitosanase II hydrolyzed 70%
      deacetylated chitosan faster than fully deacetylated chitosan. Analysis of the
      degradation products generated from partially N-acetylated chitosan showed that
      chitosanase II split GlcN-GlcN and GlcNAc-GlcN bonds but not GlcNAc-GlcNAc or
      GlcN-GlcNAc, suggesting that it is a subclass I chitosanase. It degraded
      (GlcN)(6) to produce (GlcN)(3) as main product and small amounts of (GlcN)(2) and
      (GlcN)(4). Reaction rate analyses of mono-N-acetylated chitohexaose suggested
      that the (+3) site of chitosanase II recognizes the GlcNAc residue rather than
      the GlcN residue of its substrate.

PMID- 22878199
TI  - In vivo anti-tumor activity of a new doxorubicin conjugate via alpha-linolenic
      acid.
AB  - The conventional chemotherapy agent, doxorubicin, is of limited clinical use
      because of its systemic toxicity toward normal healthy tissue. A new doxorubicin
      conjugate with alpha-linolenic acid showed good anti-tumor activity with lower
      toxicity than free doxorubicin and exhibited an active tumor-targeting profile
      due to the introduction of alpha-linolenic acid which might be an effective tumor
      targeting moiety for the modification of chemotherapeutics.

PMID- 22878200
TI  - Distribution of methanotrophs in the phyllosphere.
AB  - Plants have been reported to emit methane as well as methanol originating in
      their cell-wall constituents. We investigated methanotrophs in the phyllosphere
      by the enrichment culture method with methane as sole carbon source. We enriched
      methanotrophs from the leaves, flowers, bark, and roots of various plants.
      Analysis of the pmoA and mxaF genes retrieved from the enrichment cultures
      revealed that methanotrophs closely related to the genera Methylomonas,
      Methylosinus, and Methylocystis inhabit not only the rhizosphere but also the
      phyllosphere, together with methanol-utilizing bacteria.

PMID- 22878201
TI  - Immobilization of a thermostable cellobiose 2-epimerase from Rhodothermus marinus
      JCM9785 and continuous production of epilactose.
AB  - Cellobiose 2-epimerase (CE) efficiently forms epilactose which has several
      beneficial biological functions. A thermostable CE from Rhodothermus marinus was
      immobilized on Duolite A568 and packed into a column. Lactose (100 g/L) was
      supplied to the reactor, kept at 50  degrees C at a space velocity of 8 h(-1).
      The epilactose concentration of the resulting eluate was 30 g/L, and this was
      maintained for 13 d.

PMID- 22878202
TI  - Regulation of rat tetratricopeptide repeat domain 29 gene expression by follicle
      stimulating hormone.
AB  - We screened the gene that encodes tetratricopeptide repeat domain 29 (Ttc29) in
      the maturing rat testis. Gene expression was determined by Northern blotting of 7
      week-old rat testes, and a strong signal was detected close to the 18S rRNA band
      in addition to two weak high-molecular-weight signals. In situ hybridization
      revealed that Ttc29 was expressed primarily in the spermatocytes. We evaluated
      the effect of gonadotropin on Ttc29 expression using hypophysectomized rats. The
      pituitary was removed from 3-week-old rats, gonadotropin was injected at 5 weeks,
      and Ttc29 expression was determined at 7 weeks. Although testicular development
      and hyperplasia of interstitial cells were observed following chorionic
      gonadotropin treatment after hypophysectomy, Ttc29 expression was upregulated by
      treatment with follicle-stimulating hormone. Ttc29 encodes axonemal dynein, a
      component of sperm flagella. Taken together, these data indicate that axonemal
      dynein expression starts in the spermatocytes and is regulated by follicle
      stimulating hormone.

PMID- 22878203
TI  - Vitamin D receptor is not essential for extracellular signal-related kinase
      phosphorylation by vitamin D(3) in human Caco-2/TC7 cells.
AB  - Vitamin D(3) initiated rapid extracellular signal-related kinase (ERK)
      phosphorylation, but the contribution of vitamin D receptor (VDR) to this event
      is unclear. We investigated the use of RNA interference (RNAi) to knockdown VDR.
      RNAi downregulated VDR as well as its targeted gene expression, but vitamin D(3)
      dependent ERK phosphorylation remained. Thus VDR might not be involved in ERK
      phosphorylation by vitamin D(3).

PMID- 22878204
TI  - Effects of a chitosan intake on the fecal excretion of dioxins and fat in rats.
AB  - We evaluated the effects of the intake of various dietary fibers on the fecal
      excretion of dioxins in rats. The rats were fed five types of dietary fiber
      diets, including a chitosan diet and control diet, for 20 d and then dioxins (120
      ng/rat) were orally administered on day 15. The excretion of fecal dioxins was
      significantly higher in the chitosan group than in the control group, and dioxin
      excretion was positively correlated with fecal fat excretion. A comparison of the
      different types of chitosan showed that the efficacy of chitosan for fecal fat
      excretion was partly related to its viscosity. The chitosan intake promoted fecal
      dioxin excretion when the rats were exposed to highly toxic dioxins, and this
      excretion of fecal dioxins was related to the fecal fat excretion, suggesting
      that chitosan might be useful for reducing the adverse effects caused by
      lipophilic xenobiotics.

PMID- 22878205
TI  - Interdomain disulfide bridge in the rice granule bound starch synthase I
      catalytic domain as elucidated by X-ray structure analysis.
AB  - The catalytic domain of rice (Oryza sativa japonica) granule bound starch
      synthase I (OsGBSSI-CD) was overexpressed and the three-dimensional structures of
      the ligand-free and ADP-bound forms were determined. The structures were similar
      to those reported for bacterial and archaeal glycogen synthases, which belong to
      glycosyltransferase family 5. They had Rossmann fold N- and C-domains connected
      by canonical two-hinge peptides, and an interdomain disulfide bond that appears
      to be conserved in the Poaceae plant family. The presence of three covalent
      linkages might explain why both OsGBSSI-CD structures adopted only the closed
      domain arrangement.

PMID- 22878206
TI  - Radiocesium distribution in the tissues of Japanese Black beef heifers fed
      fallout-contaminated roughage due to the Fukushima Daiichi Nuclear Power Station
      accident.
AB  - This study examined the accumulation and tissue distribution of radioactive
      cesium nuclides in Japanese Black beef heifers raised on roughage contaminated
      with radioactive fallout due to the accident at the Fukushima Daiichi Nuclear
      Power Station on March 2011. Radiocesium feeding increased both (134)Cs and
      (137)Cs levels in all tissues tested. The kidney had the highest level and
      subcutaneous adipose had the lowest of radioactive cesium in the tissues.
      Different radioactive cesium levels were not found among parts of the muscles.
      These results indicate that radiocesium accumulated highly in the kidney and
      homogenously in the skeletal muscles in the heifers.

PMID- 22878207
TI  - Extraction of defatted rice bran with subcritical aqueous acetone.
AB  - Defatted rice bran extracts were obtained by subcritical treatment using aqueous
      acetone as extractant. Treatment with 40% (v/v) acetone at 230  degrees C for 5
      min yielded an extract with the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical scavenging activity (0.274 mmol of ascorbic acid/g of bran), total
      carbohydrate (0.188 g/g of bran), protein (0.512 g/g of bran), and total phenolic
      contents (88.2 mg of gallic acid/g of bran). The effect of treatment temperature
      (70-230  degrees C) was investigated using 40% (v/v) acetone, and the extract
      under 230  degrees C treatment showed the highest levels of all the
      determinations described above. The extracts obtained with various concentrations
      of aqueous acetone were subjected to UV absorption spectra and HPLC analysis, and
      the results showed changes in composition and polarity. Antioxidative activity
      evaluated against oxidation of bulk linoleic acid of the extract obtained with
      80% (v/v) acetone was higher than that not only of the extract from subcritical
      water treatment but also of that obtained 40% (v/v) acetone treatment.

PMID- 22878208
TI  - Enhancement of the tyrosinase inhibitory activity of Mori Cortex Radicis extract
      by biotransformation using Leuconostoc paramesenteroides PR.
AB  - Mori Cortex Radicis (MCR), the root bark of Morus alba L., consists of various
      phytochemicals and exhibits a strong inhibitory effect on tyrosinase. To enhance
      the tyrosinase inhibitory activity of MCR extract without further purification of
      bioactive compounds, whole MCR extract was biotransformed with crude enzyme
      extract from a selected lactic acid bacterium, Leuconostoc paramesenteroides PR
      (LP). Mulberroside A (MA), a major stilbene glucoside of MCR, contains two beta
      glucosyl residues at the C3 and C4' positions of oxyresveratrol (OXY). The crude
      enzyme of LP hydrolyzed the two glycosidic bonds of MA effectively, and 97.1% of
      MA was biotransformed into OXY within 2 h. Commercial almond beta-glucosidase
      hydrolyzed only one site of the two glycosidic bonds of MA, and 68.7% of MA was
      biotransformed to OXY-glucoside. The tyrosinase inhibitory activity of the crude
      extract of MCR was increased approximately 6.5-fold by biotransformation using
      LP, and the IC(50) value of the transformed MCR was 3.7 ug/mL.

PMID- 22878209
TI  - Glycosylation of trans-resveratrol by plant-cultured cells.
AB  - Plant-cultured cells of Catharanthus roseus converted trans-resveratrol into its
      3-O-beta-D-glucopyranoside, 4'-O-beta-D-glucopyranoside, 3-O-(6-O-beta-D
      xylopyranosyl)-beta-D-glucopyranoside, and 3-O-(6-O-alpha-L-arabinopyranosyl)
      beta-D-glucopyranoside. The 3-O-(6-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside
      and 3-O-(6-O-alpha-L-arabinopyranosyl)-beta-D-glucopyranoside compounds of trans
      resveratrol are both new. Incubation of plant-cultured cells of Ipomoea batatas
      and Strophanthus gratus with trans-resveratrol gave trans-resveratrol 3-O-beta-D
      glucopyranoside and trans-resveratrol 4'-O-beta-D-glucopyranoside.

PMID- 22878210
TI  - Characterization of genes involved in D-sorbitol oxidation in thermotolerant
      Gluconobacter frateurii.
AB  - Further upstream of sldSLC, genes for FAD-dependent D-sorbitol dehydrogenase in
      Gluconobacter frateurii, three additional genes (sldR, xdhA, and perA) are found:
      for a transcriptional regulator, NAD(P)-dependent xylitol dehydrogenase, and a
      transporter protein, a member of major facilitator superfamily, respectively.
      xdhA and perA but not sldR were found to be in the same transcriptional unit.
      Disruption of sldR resulted in a dramatic decrease in sldSLC promoter activity,
      indicating that it is an activator for sldSLC expression. The recombinant protein
      of XdhA expressed in Escherichia coli showed NAD-dependent dehydrogenase
      activities with xylitol and D-sorbitol, but a mutant strain defective in this
      gene showed similar activities with both substrates as compared to the wild-type
      strain. Nonetheless, the growth of the xdhA mutant strain on D-sorbitol and
      xylitol was retarded, and so was that of a mutant strain defective in perA. These
      results indicate that xdhA and perA are involved in assimilation of D-sorbitol
      and xylitol.

PMID- 22878211
TI  - The respiratory system of the piezophile Photobacterium profundum SS9 grown under
      various pressures.
AB  - It is known that the facultative piezophile Shewanella violacea DSS12 alters its
      respiratory components under the influence of hydrostatic pressure during growth.
      This can be considered one of the mechanisms of bacterial adaptation to high
      pressure. In this study, we investigated the respiratory system of another well
      studied piezophile, Photobacterium profundum SS9. We analyzed cytochrome
      contents, the expression of genes encoding respiratory components in P. profundum
      SS9 grown under various conditions, and the pressure dependency of the terminal
      oxidase activities. Activity was more tolerant of relatively high pressures, such
      as 125 MPa when the cells were grown under high pressure as compared with cells
      grown under atmospheric pressure. Such properties observed are similar to the
      case of S. violacea. However, the contents of the cytochromes and expression of
      the respiratory genes were not influenced by growth pressure in P. profundum SS9,
      inconsistent with the case of S. violacea. We suggest that the mechanism of the
      piezoadaptation of the respiratory system of P. profundum SS9 differs from that
      of S. violacea, as described above, and that each strain chooses its own
      strategy.

PMID- 22878212
TI  - Enhanced production of ganoderic acids and cytotoxicity of Ganoderma lucidum
      using solid-medium culture.
AB  - Submerged cultures of Ganoderma lucidum are used to produce fungal mycelium,
      which is used as a functional food and in the production of various
      triterpenoids, including ganoderic acids (GAs). Specific culture approaches that
      produce fungal mycelium with high levels of GAs and good biological activity are
      critical in the functional food industry. In this study, a solid-medium culture
      approach to producing mycelium was compared to the submerged culture system.
      Production of GAs, biomass, intracellular polysaccharides, and cytotoxicity of
      the cultured mycelium were compared as between solid and submerged culture.
      Growing G. lucidum strains on solid potato dextrose agar medium increased
      biomass, the production of ganoderic acid 24 (lanosta-7,9(11), 24-trien-3alpha-o1
      26-oic acid), GAs, and total intracellular polysaccharides as compared to fungi
      grown in submerged culture. Triterpenoid-enriched methanol extracts of mycelium
      from solid-medium culture showed higher cytotoxicity than those from submerged
      culture. The IC(50) values of methanol extracts from solid-medium culture were
      11.5, 8.6, and 9.9 times less than submerged culture on human lung cancer cells
      CH27, melanoma cells M21, and oral cancer cells HSC-3 respectively. The squalene
      synthase and lanosterol synthase coding genes had higher expression on the
      culture of solid potato dextrose medium. This is the first report that solid
      medium culture is able to increase GA production significantly as compared to
      submerged culture and, in the process, produces much higher biological activity.
      This indicates that it may be possible to enhance the production of GAs by
      implementing mycelium culture on solid medium.

PMID- 22878213
TI  - Lung and breast cancer mortality among women in France: future trends.
AB  - Estimates of mortality in future years are crucial for communication, prevention
      and anticipation related to the burden of diseases and for developing scenarios
      studying the effects of reducing environmental exposure. The aim of this study is
      to project observed trends of mortality in France for lung and breast cancer
      among females to 2021. Projections of mortality rates are based on a Bayesian age
      period-cohort model and a Poisson distribution. We used cancer mortality data
      from the French mortality register (period 1977-2006) and population data from
      population registers (estimated for 1977-2006 and projected for period 2007-2021
      using five scenarios: largest, smallest, youngest, older, average population).
      Alternative models were tested (generalized additive model, negative binomial
      distribution). For the average population scenario, lung and breast cancer
      mortality rates age-standardized to the world population, are respectively: 11.5
      per 10(5) women (Credibility interval: 10.3-12.8) and 15.9 (14.4-17.6) in 2007
      2011, 14.6 (11.7-18.1) and 14.5 (11.6-18.0) in 2012-2016, 18.2 (12.6-26.0) and
      13.3 (9.1-18.9) in 2017-2021. Projections show an ongoing increase for lung
      cancer and decrease for breast cancer mortality rates, which are expected to be
      equal in 2012-2016. Compared projections of these two cancers using a similar
      method had not been done before. Aggressive prevention strategies targeting
      smoking among women are needed to control this fast growing epidemic of avoidable
      cancer. Planning of health care capacity for diagnosis and treatment of cancer
      among females is also necessary.

PMID- 22878214
TI  - Low quality of life as an additional criterion for the clinical diagnosis of
      heart failure in primary care.
AB  - OBJECTIVE: The aim of this study is to estimate the association of shortness of
      breath (SOB), fatigue and bilateral lower limb edema (LLE) - typical symptoms of
      HF - with quality of life (QOL) dimensions, measured by the Medical Outcomes
      Study 36-Item Short Form Health Survey (SF-36). METHODS: This cross-sectional
      study was conducted as part of the CAMELIA study (Cardiometabolic Renal Familial
      Study), which involved families covered by the Family Doctor Program (FDP) in
      Niteroi, Rio de Janeiro, Brazil. The study included 455 patients aged 30 and
      over, assessed by questionnaire, medical consultation, and blood and urine tests.
      RESULTS: The prevalence of symptoms was: fatigue 56.9%, SOB 22.6% and LLE 16.9%.
      There were independent and statistically significant associations between SOB and
      fatigue and all SF-36 dimensions, excepting emotional performance and SOB
      (p<0.10). CONCLUSION: The combination of SOB and fatigue with low QOL can
      increase the positive predictive value for a clinical diagnosis of HF and is a
      possible alternative for prioritizing patients for closer investigation in a
      primary care setting.

PMID- 22878215
TI  - Experimental gestational hypothyroidism evokes hypertension in adult offspring
      rats.
AB  - Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to
      investigate the impact of experimental gestational hypothyroidism (EGH) on
      cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH
      was induced with methimazole (MMI) 0.02% in drinking water from day 9 of
      gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n=13)
      or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for
      the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic
      arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To
      investigate the balance of ANS, we established the high (HF) and low frequency
      (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased
      MAP (130.2 +/- 2.0 vs 108.8 +/- 3.0 mmHg, p<0.001), SAP (157.3 +/- 2.9 vs 135.7
      +/- 4.5mm Hg, p<0.001) and DAP (109.7 +/- 1.9 vs 88.4 +/- 2.6 mmHg, p<0.001) when
      compared to OWTD, and had lower HR (355.1 +/- 8.9 vs 386.8 +/- 9.2 bpm, p<0.05).
      After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher
      (7.2 +/- 0.8 vs 4.0 +/- 0.6 mmHg(2), p<0.01) in OMTD under spontaneous condition.
      Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old
      offspring, probably due to increased sympathetic modulation of vessels, which is
      suggested by the higher LF of SAP. These findings suggest a critical role of
      maternal THs in the development of fetal cardiovascular and autonomic nervous
      systems.

PMID- 22878216
TI  - CKIP-1: a scaffold protein and potential therapeutic target integrating multiple
      signaling pathways and physiological functions.
AB  - The PH domain-containing casein kinase 2 interacting protein-1 (CKIP-1, also
      known as PLEKHO1) acts as a scaffold protein mediating interactions with multiple
      proteins, including CK2alpha, CPalpha, AP-1/c-Jun, Akt, ATM, IFP35/Nmi and
      Smurf1. CKIP-1 functions through different ways, such as plasma membrane
      recruitment, transcriptional activity modulation and posttranscriptional
      modification regulation. Moreover, the subcellular localization of CKIP-1 is
      determined by several key amino acids in a cell type dependent style, and the
      nucleus/plasma membrane shuttle of CKIP-1 is regulated by different cell
      stresses. As an adaptor protein, CKIP-1 is involved in various important
      signaling pathways, controlling cell growth, apoptosis, differentiation,
      cytoskeleton and bone formation. Strikingly, CKIP-1 has been recently
      demonstrated to be a promising target for treatment of osteoporosis in rat
      models. In addition, more evidences suggest that CKIP-1 might also function as a
      potential tumor suppressor.

PMID- 22878217
TI  - Tsetse flies: their biology and control using area-wide integrated pest
      management approaches.
AB  - Tsetse flies are the cyclical vectors of trypanosomes, the causative agents of
      'sleeping sickness' or human African trypanosomosis (HAT) in humans and 'nagana'
      or African animal trypanosomosis (AAT) in livestock in Sub-saharan Africa. Many
      consider HAT as one of the major neglected tropical diseases and AAT as the
      single greatest health constraint to increased livestock production. This review
      provides some background information on the taxonomy of tsetse flies, their
      unique way of reproduction (adenotrophic viviparity) making the adult stage the
      only one easily accessible for control, and how their ecological affinities,
      their distribution and population dynamics influence and dictate control efforts.
      The paper likewise reviews four control tactics (sequential aerosol technique,
      stationary attractive devices, live bait technique and the sterile insect
      technique) that are currently accepted as friendly to the environment, and
      describes their limitations and advantages and how they can best be put to
      practise in an IPM context. The paper discusses the different strategies for
      tsetse control i.e. localised versus area-wide and focusses thereafter on the
      principles of area-wide integrated pest management (AW-IPM) and the phased
      conditional approach with the tsetse project in Senegal as a recent example. We
      argue that sustainable tsetse-free zones can be created on Africa mainland
      provided certain managerial and technical prerequisites are in place.

PMID- 22878218
TI  - [A review of assessment of fitness for work and adjustments for health and safety
      at worksites overseas].
AB  - OBJECTIVE: In this research, we reviewed studies about assessment of fitness for
      work and adjustments for health and safety at worksites overseas. METHODS: We
      systematically searched PubMed (1980-2010) using keywords related to fitness for
      work. The collected studies are discussed with respect to the country, timing of
      medical examinations, health problems of workers, occupations, categories of
      health level in workers, criteria for assessment of fitness for work, and the
      decision-making process related to accommodations at work. RESULTS: Seventy
      articles were identified that met the inclusion criteria. They focused on two key
      points related to assessing fitness for work: 1) safety and risk to workers
      themselves, to other workers and the public, and 2) ability to perform in
      potentially dangerous situations, such as those encountered by the military and
      firemen. Employers were required to provide reasonable accommodations for
      disabled or sick workers. The following steps were taken to make accommodation
      decisions: 1) analysis of job requirements; 2) worker analysis, including
      evaluation of work limitations or risks related to disabilities or illness; 3)
      choice of necessary adjustments at work, based on reasonable accommodations
      decided during talks between the disabled or sick workers and employers,
      including feasibility, effectiveness, and costs of such adjustments; 4) judgment
      of fitness for work based on steps 1 to 3, and opinions of specialists in various
      fields. CONCLUSION: In this investigation, we could not find any clear criteria
      for judgments about fitness for work or numerical criteria for adjustments at
      worksites after medical examinations of employees. However, we confirmed the
      following. Assessing fitness for work should be based on a comparison of workers'
      health with the risks and demands of the job. In addition, doctors should have
      the ability to offer opinions on adjustments at worksites. The employer's
      obligation to provide reasonable accommodations is attracting more attention in
      Japan. To make adjustments for health and safety at worksites for all workers,
      the procedures and important issues must be determined as well as criteria of
      judgments or numerical criteria. Moreover, doctors should provide opinions about
      adjustments at worksites. Therefore, they need more training in assessing fitness
      for work.

PMID- 22878219
TI  - [Turnover of full-time occupational physicians in Japan in the period 2002-2008:
      a component model survey].
AB  - OBJECTIVE: Recently, the number of occupational physicians has greatly increased
      compared to other types of physician in Japan, and the number of unfilled job
      vacancies remains high, suggesting a higher turnover of occupational physicians.
      Job turnover and seniority are important indices for measuring the balance of
      vacancies and applicants, as well as for improving occupational health services;
      however, job turnover and career moves of occupational physicians are currently
      not known. METHOD: Based on a component model study of physicians, dentists and
      pharmacists, we made a component model of 4 levels (national, prefectural, urban,
      and municipal levels) and estimated the turnover and regional migration of
      occupational physicians. As a reference for the component models, we used the
      2008/2006 cross-tabulation data of each type of physician published by the
      Ministry of Health, Labour and Welfare. RESULTS: The municipality level component
      model fitted the data best. The increase in occupational physicians for the 2 yr
      was 283-348, and the decrease was 202-222, indicating that 55-65% of occupational
      physicians quit their post within 2 yr. CONCLUSIONS: The propensity for short
      tenure is observed not only in occupational medicine, but also in emergency and
      rehabilitation medicine. It is suspected that 80% of new occupational physicians,
      except those graduating from the University of Occupational and Environmental
      Health, quit their positions within two years. This is a remarkably short tenure
      period compared to the 5.6 yr average seniority of physicians reported in the
      Basic Survey of Wage Structure. The reasons for the high job turnover of
      occupational physicians are thought to be unrelated to income or license renewal.
      We need to survey the actual reasons for the short tenure of occupational
      physicians to provide insights into lifetime education and career organization of
      occupational physicians.

PMID- 22878220
TI  - Orthognathic surgery for the complete rehabilitation of Moebius patients:
      principles, timing and our experience.
AB  - Moebius syndrome is a rare disorder found in approximately 1/100,000 neonates and
      the treatment of facial palsy is now well established worldwide and consists of
      free-muscle transplants reinnervated with motor nerves. Dentofacial deformities
      are often detected in Moebius patients, and different degrees of micrognathia are
      often present, particularly in patients with complete expressions of Moebius
      syndrome. However only two published reports have described the surgical
      treatment of such anomalies in these patients; in both cases, the suggested
      approach consisted of orthognathic surgery followed by soft-tissue management. In
      this paper we discuss the indications and correct timing of orthognathic surgery
      and suggest to perform facial animation at an early age and then to wait for the
      completion of maxillofacial skeletal growth before performing orthognathic
      surgery. Finally, facial animation should precede orthognathic surgery in adult
      patients to prevent lower lip deformities and to ensure more predictable and
      satisfactory results.

PMID- 22878221
TI  - A clinically-feasible protocol for using human platelet lysate and mesenchymal
      stem cells in regenerative therapies.
AB  - The transplantation of human stem cells seeded on biomaterials holds promise for
      many clinical applications in cranio-maxillo-facial tissue engineering and
      regenerative medicine. However, stem cell propagation necessary to produce
      sufficient cell numbers currently utilizes fetal calf serum (FCS) as a growth
      supplement which may subsequently transmit animal pathogens. Human platelet
      lysate (HPL) could potentially be utilized to produce clinical-grade stem cell
      loaded biomaterials as an appropriate FCS substitute that is in line with
      clinically-applicable practice. The goal of this study was to investigate whether
      HPL can be successfully used to propagate human mesenchymal stem cells (HMSCs)
      seeded on clinically-approved collagen materials under clinically-applicable
      conditions using FCS as a control. HMSCs were isolated from bone marrow and
      cultured in the presence of 10% FCS or 10% HPL. Characterization of HMSCs was
      performed by flow cytometry and through osteogenic and adipogenic differentiation
      assays. Proliferative capacity of HMSCs on both matrices was investigated by
      mitochondrial dehydrogenase assays (WST) and tissue coverage scanning electron
      microscopy (SEM). The isolated HMSC differentiated into osteogenic and adipogenic
      cells authenticating the multipotentiality of the HMSCs. WST tests and the SEM
      images demonstrated that HPL was generally superior to FCS in promoting growth of
      seeded HMSCs. For all other tests HPL supported HMSCs at least equal to FCS. In
      conclusion, HPL is an effective growth factor to allow expansion of clinical
      grade HMSCs on clinically-approved biomaterials for maxillofacial and oral
      implantology applications.

PMID- 22878222
TI  - Self reported adherence to a home-based exercise programme among people with
      Parkinson's disease.
AB  - BACKGROUND: There is an extensive literature addressing compliance with
      medication, techniques to measure, and ways to improve it. In comparison the
      literature concerning adherence to exercise programmes agreed with a
      physiotherapist is limited. OBJECTIVE: We estimate the percentage of exercise
      repetitions completed of those agreed with a physiotherapist in the context of a
      six week personalized exercise programme to reduce falling in people with
      Parkinson's disease, and examine patient characteristics that predict adherence.
      METHODS: Secondary analysis of data collected during a randomized controlled
      trial. Participants allocated to receive the exercise programme self-reported the
      number of repetitions of prescribed strengthening, range of movement and balance
      exercises they had completed in daily dairies. Indoor or outdoor walking was also
      prescribed but in terms of target distances or lengths of time, and was not
      included in our analysis. RESULTS: On average the 70 participants allocated to
      the exercise programme reported completing 79% (95% confidence interval 73%-86%)
      of the prescribed number of repetitions of their exercises. The percentage of
      exercises completed varied depending on the specific exercise prescribed, and on
      participant characteristics: those who were older, in poorer health and with
      anxiety, depression, or mental heath problems reported lower adherence to
      exercise. CONCLUSION: Several of the factors we found to reduce adherence to
      exercise have been shown by others to reduce compliance with antiparkinsonian
      medication, but we found adherence decreased with age in contrast to the pattern
      of better compliance with medication amongst older people with Parkinson's
      disease reported previously.

PMID- 22878223
TI  - Sleep paralysis in Parkinson's disease.

PMID- 22878224
TI  - Effect of sigma1 receptor antagonism on ethanol and natural reward seeking.
AB  - sigma1 Receptors have been implicated in cognitive function, anxiety, depression,
      and the regulation of stress responses. In addition, sigma1 receptors have been
      shown to participate in the behavioral and motivational effects of
      psychostimulants. Recent studies have shown that sigma1 receptor antagonism
      prevents ethanol-induced conditioned place preference in mice and excessive
      drinking in alcohol-dependent or alcohol-preferring rats. Therefore, this study
      was designed to determine whether this role for sigma1 receptors extends to
      ethanol-seeking behavior using an animal model of relapse and tested whether the
      suppressant effect of a potent sigma1 receptor antagonist, BD1047, generalizes to
      natural reward-seeking behavior. Two separate groups of rats were trained to
      orally self-administer 10% (w/v) ethanol or a highly palatable reinforcer,
      3%/0.125% (w/v) glucose/saccharin (SuperSac), in the presence of a discriminative
      stimulus (S). Following extinction, during which the reinforcers and S were
      withheld, the presentation of the ethanol or SuperSac S produced comparable
      recovery of responding. BD1047 (1-20 mg/kg) exerted similar behavioral effects on
      both ethanol S-induced and SuperSac S-induced reinstatement, with the prevention
      of conditioned reinstatement only at the highest BD1047 dose. The present results
      show that sigma1 receptor blockade under the present conditions exerts similar
      effects on conditioned reinstatement induced by ethanol-related and SuperSac
      related stimuli, suggestive of overlapping neural mechanisms that control ethanol
      and natural reward seeking.

PMID- 22878225
TI  - Cytotoxic podophyllotoxin type-lignans from the steam bark of Bursera fagaroides
      var. fagaroides.
AB  - The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides
      displayed potent cytotoxic activity against four cancer cell lines, namely KB
      (ED50 = 9.6 * 10(-2) MUg/mL), PC-3 (ED50 = 2.5 * 10(-1) MUg/mL), MCF-7 (ED50 =
      6.6 MUg/mL), and HF-6 (ED50 = 7.1 * 10(-3) MUg/mL). This extract also showed anti
      tumour activity when assayed on mice inoculated with L5178Y lymphoma cells.
      Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin
      type lignans identified as podophyllotoxin (1), beta-peltatin-A-methylether (2),
      5'-desmethoxy-beta-peltatin-A-methylether (3), desmethoxy-yatein (4),
      desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D
      and 2DNMR and FAB-MS analyses, and comparison with reported values. All the
      isolated compounds showed potent cytotoxic activity in the cell lines tested,
      especially compound 3, which exhibited greater activity than camptothecin and
      podophyllotoxin against PC-3 (ED50= 1.0 * 10(-5) MUg/mL), and KB (ED50 = 1.0 *
      10(-5) MUg/mL). This is the first report of the isolation of podophyllotoxin and
      its acetate in a Bursera species.

PMID- 22878226
TI  - Three new myrsinol diterpenes from Euphorbia prolifera and their neuroprotective
      activities.
AB  - Three new myrsinol diterpenes were isolated from the roots of Euphorbia
      prolifera. Their structures were elucidated as 2alpha-O-isobutyryl
      3beta,5alpha,7beta,10,15beta-penta-O-acetyl-14alpha-O-benzoyl-10,18
      dihydromyrsinol (1), 2alpha-O-isobutyryl-3beta-O-propion-yl
      5alpha,7beta,10,15beta-tetra-O-acetyl-10,18-dihydromyrsinol (2), and
      2alpha,14alpha-di-O-benzoyl-3beta,5alpha,7beta,10,15beta-penta-O-acetyl-10,18
      dihydromyrsinol (3) on the basis of spectroscopic data analyses (IR, ESI-MS, HR
      ESI-MS, and 1D and 2D NMR). Their neuroprotective activities were evaluated and
      compounds 1 and 2 showed neuroprotective effects against MPP+ -induced neuronal
      cell death in SH-SY5Y cells.

PMID- 22878227
TI  - Hologram QSAR models of 4-[(diethylamino)methyl]-phenol inhibitors of
      acetyl/butyrylcholinesterase enzymes as potential anti-Alzheimer agents.
AB  - Hologram QSAR models were developed for a series of 36 inhibitors (29 training
      set and seven test set compounds) of acetyl/butyrylcholinesterase (AChE/BChE)
      enzymes, an attractive molecular target for Alzheimer's disease (AD) treatment.
      The HQSAR models (N = 29) exhibited significant cross-validated (AChE, q2 =
      0.787; BChE, q2 = 0. 904) and non-cross-validated (AChE, r2 = 0.965; BChE, r2=
      0.952) correlation coefficients. The models were used to predict the inhibitory
      potencies of the test set compounds, and agreement between the experimental and
      predicted values was verified, exhibiting a powerful predictive capability.
      Contribution maps show that structural fragments containing aromatic moieties and
      long side chains increase potency. Both the HQSAR models and the contribution
      maps should be useful for the further design of novel, structurally related
      cholinesterase inhibitors.

PMID- 22878228
TI  - Chemical composition and in vitro evaluation of the antioxidant and antimicrobial
      activities of Eucalyptus gillii essential oil and extracts.
AB  - In this study, essential oil and various extracts (hexane, petroleum ether,
      acetone, ethanol, methanol and water) of Eucalyptus gilii were screened for their
      chemical composition, antimicrobial and antioxidant activities. The essential oil
      chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS)
      and gas chromatography-flame ionization detection (GC-FID), respectively. Thirty
      four compounds were identified, corresponding to 99.5% of the total essential
      oil. Tannins [104.9-251.3 g catechin equivalent (CE)/Kg dry mass], flavonoids
      [3.3-34.3 g quercetin equivalent (QE)/Kg dry mass], phenolics [4.7-216.6 g gallic
      acid equivalent (GAE)/Kg dry mass] and anthocyannins [1.2-45.3 mg cyanidin-3
      glucoside equivalent (C3GE)/Kg dry mass] of various extracts were investigated.
      Free radical scavenging capacity of all samples was determinedt. In the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) assay, the IC50 of essential oil was 163.5 +/-
      10.7 mg/L and in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonate (ABTS)
      assay, it was 94.7 +/- 7.1 mg/L. Among the various extracts, the water extract
      showed the best result (IC50 = 11.4 +/- 0.6 mg/L) in the DPPH assay which was
      comparable to vitamin C (IC50 = 4.4 +/- 0.2 mg/L). The antimicrobial activities
      were evaluated against different bacterial and fungal strains. Gram positive
      bacteria were found to be more sensitive to the essential oil and extracts than
      Gram negative ones. Anthocyanins seem to have a major effect on the growth of
      Bacillus subtilis (R2 = 0.79). A significant antifungal activity was observed
      against the yeast and fungi. Correlations between chemical composition and
      antioxidant activities were studied and R2 values were about 0.96 for the effect
      of phenolics on the DPPH assay.

PMID- 22878229
TI  - Invited commentary on central hypersensitivity in patients with subacromial
      impingement syndrome.
AB  - Pain pressure threshold (PPT) measurement by handheld algometer has been
      validated as a tool to identify and quantitate myofascial pain sites in an
      individual. The average of 3 readings at a given muscle site is used, so the
      standard error of measurement of these devices must be considered when
      determining whether PPT differences between muscle sites represent true changes.
      This commentary discusses this issue.

PMID- 22878230
TI  - Early aquatic physical therapy improves function and does not increase risk of
      wound-related adverse events for adults after orthopedic surgery: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To investigate whether early postoperative aquatic physical therapy
      is a low-risk and effective form of physical therapy to improve functional
      outcomes after orthopedic surgery. DATA SOURCES: Databases MEDLINE, CINAHL, AMED,
      Embase, and PEDro were searched from the earliest date available until October
      2011. Additional trials were identified by searching reference lists and citation
      tracking. STUDY SELECTION: Controlled trials evaluating the effects of aquatic
      physical therapy on adverse events for adults <3 months after orthopedic surgery.
      Two reviewers independently applied inclusion and exclusion criteria, and any
      disagreements were discussed until consensus could be reached. Searching
      identified 5069 potentially relevant articles, of which 8 controlled trials with
      287 participants met inclusion criteria. DATA EXTRACTION: A predefined data
      extraction form was completed in detail for each included study by 1 reviewer and
      checked for accuracy by another. Methodologic quality of included trials was
      assessed independently by 2 reviewers using the PEDro scale. DATA SYNTHESIS:
      Pooled analyses were performed using random effects model with inverse variance
      methods to calculate standardized mean differences (SMDs) and 95% confidence
      intervals (CIs) (continuous outcomes) and risk difference and 95% CIs
      (dichotomous outcomes). When compared with land-based physical therapy, early
      aquatic physical therapy does not increase the risk of wound-related adverse
      events (risk difference=.01, 95% CI -.05 to .07) and results in improved
      performance of activities of daily living (SMD=.33, 95% CI=.07-.58, I(2)=0%).
      There were no significant differences in edema (SMD=-.27, 95% CI=-.81 to .27,
      I(2)=58%) or pain (SMD=-.06, 95% CI=-.50 to .38, I(2)=32%). CONCLUSIONS: After
      orthopedic surgery aquatic physical therapy improves function and does not
      increase the risk of wound-related adverse events and is as effective as land
      based therapy in terms of pain, edema, strength, and range of motion in the early
      postoperative period.

PMID- 22878231
TI  - Effects on decreasing upper-limb poststroke muscle tone using transcranial direct
      current stimulation: a randomized sham-controlled study.
AB  - OBJECTIVE: To assess the efficacy of transcranial direct current stimulation
      (tDCS) on decreasing upper-limb (UL) muscle tone after stroke. DESIGN: A
      prospective, sham-controlled, randomized controlled trial with 4-weeks follow-up.
      Randomization into the tDCS group or the control group. SETTING: Rehabilitation
      education and research hospital. PARTICIPANTS: Inpatients (N=90, 45 per group;
      age range, 15-70y; 69 men, 21 women; duration of stroke, 2-12mo) with poststroke
      UL spasticity. No participant withdrew because of adverse effects. INTERVENTION:
      The tDCS group received tDCS to the primary sensorimotor cortex of the affected
      side with cathodal stimulation, 20 minutes per day, 5 days per week, for 4 weeks
      and conventional physical therapy. The control group received sham stimulation
      (same area as the tDCS group) and conventional physical therapy. MAIN OUTCOME
      MEASURES: Modified Ashworth scale (MAS), Fugl-Meyer Assessment of motor recovery,
      and Barthel Index. All outcomes were measured at admission, after treatment, and
      after follow-up. A clinically important difference (CID) was defined as a
      reduction of >=1 in the MAS score. RESULTS: Compared with the sham tDCS group,
      the active tDCS group had significantly more patients with a clinically important
      difference after treatment (80% and 78% vs 6% and 9%) and at 4-week follow-up
      (84% and 82% vs 7% and 4%), and UL motor function and activities of daily living
      (ADL) assessment improved more significantly in the active tDCS group (Fugl-Meyer
      Assessment of motor recovery from 12 [range, 4-26] to 22 [range, 7-50] to 32
      [range, 28-41], Barthel Index from 55 [range, 0-85] to 85 [range, 5-100] to 90
      [range, 10-100 vs Fugl-Meyer Assessment of motor recovery from 8 [range, 3-34] to
      10 [range, 8-25] to 15 [range, 6-40], Barthel Index from 55 [range, 25-95] to 65
      [range, 30-100] to 75 [range, 40-100], respectively, P<.01). CONCLUSIONS: UL
      muscle tone after stroke can be decreased using cathodal tDCS. Combined with
      conventional physical therapy, tDCS appears to improve motor function and ADL.
      Cathodal tDCS over ipsilesional primary sensorimotor cortex may inhibit primary
      sensorimotor cortex hyperactivation, resulting in significant reductions in
      muscle tone.

PMID- 22878232
TI  - DMCM, a benzodiazepine site inverse agonist, improves active avoidance and
      motivation in the rat.
AB  - There are several modulatory sites at GABA(A) receptors, which mediate the
      actions of many drugs, among them benzodiazepine. Three kinds of allosteric
      modulators act through the benzodiazepine binding site: positive (agonist),
      neutral (antagonist), and negative (inverse agonist). The goal of the present
      study was to examine the influence of the inverse agonist methyl 6,7-dimethoxy-4
      ethyl-beta-carboline-3-carboxylate (DMCM) acting on alpha GABA(A) receptor and
      compare its dose-response effects on memory and depression-like behavior. We
      independently studied the effects of DMCM (0.05-1.0 mg/kg) on retention versus
      acquisition of active avoidance and depression-like behavior in the forced swim
      test. Throughout the study, drugs were given intraperitoneally, 30 min before
      testing. ANOVA has showed that treatment with DMCM significantly affected
      retrieval of avoidance response (p<0.05), exerted promnesic effects in inverted U
      shape manner. Dunnett's test indicated that the DMCM avoidance-facilitatory dose
      was 0.1mg/kg. At the dose facilitating retrieval of avoidance memory, DMCM
      significantly (p<0.05, comparison of regression coefficients by Student's t-test)
      and progressively increased acquisition rate during 5 days training, compared to
      the saline group. In forced swim test, ANOVA indicated statistically significant
      effects of DMCM (p<0.05). Dunnett's analysis showed that DMCM significantly
      decreased immobility time at the dose of 0.1mg/kg, exerted acute antidepressant
      like effects. Our results experimentally support the findings that under certain
      circumstances, nonselective benzodiazepine site inverse agonists, produce memory
      enhancing and antidepressant-like effects. The molecular and neuronal substrates
      linking the actions of specific GABA-benzodiazepine receptor complex subunits
      remains to be further elucidated.

PMID- 22878234
TI  - Assessment of nutritional status and analytical methods.

PMID- 22878235
TI  - A new approach to establishing dietary energy reference values.
AB  - PURPOSE OF REVIEW: To describe the methodology behind the new UK Dietary
      Recommendations for Energy. RECENT FINDINGS: Large interindividual variation in
      discretionary activity prevents prediction of energy expenditure, [total energy
      expenditure (TEE)], as a function of physical activity levels (PALs), [e.g. TEE =
      PAL * basal metabolic rate (BMR)] with the previously assumed accuracy. An
      alternative simplified approach derives PAL values in terms of population median
      and values for those exhibiting less or more activity (25th and 75th centiles)
      from suitable reference doubly labelled water (DLW) data. DLW data sets were used
      to identify PAL values: for adults, from two large randomized studies of urban
      populations (n = 929), and for children (aged 1-3, 3 to less than 10 and 10-18
      years), from all published studies reporting mean values (n = 170 studies, 2502
      patients) from which PAL values were reported or could be derived. Values for TEE
      were then derived from anthropometric determinants of BMR and PAL, and
      prescriptive estimated average requirement, (EAR) values were calculated on the
      basis of healthy body weights: BMI = 22.5 kg/m for adults and reference growth
      data for children. Energy costs of tissue energy deposition were modelled as a
      simple 1% increase in PAL values for children within the three age groups.
      SUMMARY: The model for calculation of the EAR is simplified and widely applicable
      in most population settings.

PMID- 22878233
TI  - Mitochondrial fission induces glycolytic reprogramming in cancer-associated
      myofibroblasts, driving stromal lactate production, and early tumor growth.
AB  - Recent studies have suggested that cancer cells behave as metabolic parasites, by
      inducing oxidative stress in adjacent normal fibroblasts. More specifically,
      oncogenic mutations in cancer cells lead to ROS production and the "secretion" of
      hydrogen peroxide species. Oxidative stress in stromal fibroblasts then induces
      their metabolic conversion into cancer-associated fibroblasts. Such oxidative
      stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in
      fibroblasts, resulting in the local production of high-energy mitochondrial fuels
      (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are
      then transferred to cancer cells, where they are efficiently burned via oxidative
      mitochondrial metabolism (OXPHOS). We have termed this new energy-transfer
      mechanism "Two-Compartment Tumor Metabolism", to reflect that the production and
      consumption of nutrients (L-lactate and other catabolites) is highly
      compartmentalized. Thus, high-energy onco-catabolites are produced by the tumor
      stroma. Here, we used a genetic approach to stringently test this energy-transfer
      hypothesis. First, we generated hTERT-immortalized fibroblasts which were
      genetically re-programmed towards catabolic metabolism. Metabolic re-programming
      towards glycolytic metabolism was achieved by the recombinant over-expression of
      MFF (mitochondrial fission factor). MFF over-expression results in extensive
      mitochondrial fragmentation, driving mitochondrial dysfunction. Our results
      directly show that MFFfibroblasts undergo oxidative stress, with increased ROS
      production, and the onset of autophagy and mitophagy, both catabolic processes.
      Mechanistically, oxidative stress induces autophagy via NF-kB activation, also
      providing a link with inflammation. As a consequence MFF-fibroblasts showed
      intracellular ATP depletion and the extracellular secretion of L-lactate, a
      critical onco-catabolite. MFF-fibroblasts also showed signs of myofibroblast
      differentiation, with the expression of SMA and calponin. Importantly, MFF
      fibroblasts signficantly promoted early tumor growth (up to 6.5-fold), despite a
      20% overall reduction in angiogenesis. Thus, catabolic metabolism in cancer
      associated fibroblasts may be a critical event during tumor intiation, allowing
      accelerated tumor growth, especially prior to the onset of neoangiogenesis.

PMID- 22878236
TI  - Metabolism of mice and men:  mathematical modeling of body weight dynamics.
AB  - PURPOSE OF REVIEW: Dynamic interrelationships between food intake, energy
      expenditure, energy partitioning, and metabolic fuel selection underlie changes
      in body weight and composition. A quantitative understanding of these
      interrelationships is becoming increasingly important given the rise of the
      worldwide obesity epidemic and the widespread interest in weight management. This
      review describes how mathematical models offer a quantitative framework for
      integrating dynamic physiological and behavioral data underlying body weight
      dynamics in both humans and mice. RECENT FINDINGS: Mathematical models have
      provided important insights regarding the drivers of the obesity epidemic, how
      metabolism adapts to different diets, the predicted magnitude and variability of
      weight change, and why mouse models have obesity phenotypes. Because mathematical
      models are constrained by conservation laws, they can also be used to infer
      physiological variables that are difficult to measure directly. SUMMARY:
      Mathematical models can help improve our understanding of the dynamic energy and
      macronutrient imbalances that give rise to changes in body weight and composition
      over time. The model development process can also highlight important knowledge
      gaps and model simulations can help design and predict the results of key new
      experiments to fill those gaps.

PMID- 22878237
TI  - Epigenetics:  are there implications for personalised nutrition?
AB  - PURPOSE OF REVIEW: This review critically evaluates recent advances in
      understanding the role of epigenetics in nutrition. Findings from animal models
      and human cohorts are discussed in the context of whether or not epigenetics may
      be an important factor in the progress towards the goal of personalised
      nutrition. RECENT FINDINGS: Maternal dietary fat, folic acid, protein and total
      energy intakes induce altered epigenetic regulation of specific genes in the
      offspring which are associated with altered tissue function. Passage of induced
      phenotypic and epigenetic traits between generations involves intergenerational
      modifications in the interaction between maternal phenotype and environment. The
      methylation of specific CpG loci in fetal tissues is associated with differential
      future risk of type 2 diabetes mellitus, and variation in adiposity and height.
      Methylation of specific CpGs in adult blood also marks differential risk of type
      2 diabetes mellitus and breast cancer. Exercise induces acute changes in the
      methylation of genes in muscle. SUMMARY: Recent advances indicate that epigenetic
      variation is an important influence on interactions between nutrients and the
      genome, which modify disease risk. In contrast to the interaction between
      nutrition and gene polymorphisms, epigenetic variation can be modified by
      nutritional interventions to improve health outcomes.

PMID- 22878238
TI  - Taking a metagenomic view of human nutrition.
AB  - PURPOSE OF REVIEW: Humans harbor microbial communities throughout the
      gastrointestinal tract that both respond to and modify orally ingested
      macronutrients, bioactive compounds, and xenobiotics; for example, the metabolism
      of polyphenols, heterocyclic amines, and phosphatidylcholine. However, the
      composition and physiological impact of our diet is also linked to the methods of
      food production, preparation, and consumption, which are altered by environmental
      and food-borne microbial communities. Metagenomic analyses spanning these various
      steps in human nutrition will be critical for a more comprehensive view. RECENT
      FINDINGS: Studies in humans and animal models have highlighted the key role that
      diet plays in shaping gut microbial ecology, and how the trillions of microbes in
      the gut (microbiota) enable the digestion of substrates inaccessible to our own
      human enzymes. These transformations have been implicated in a variety of
      diseases and disorders, ranging from obesity, inflammatory bowel disease, heart
      disease, to cancer. SUMMARY: In order to move towards personalized nutrition and
      medicine, it is important to take into account both our host and microbial
      genomes. The resulting metagenomic view of human nutrition, ranging from the
      initial biotransformations of food to digestion and the end result on human
      physiology, could have wide-ranging implications for food science, human
      evolutionary biology, and microbial ecology.

PMID- 22878239
TI  - Nutrition and the gastrointestinal tract.

PMID- 22878240
TI  - Improving dietary patterns in patients with nonalcoholic fatty liver disease.
AB  - PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is the liver epidemic
      of our time. Diet strongly influences its development and should be a component
      of any treatment plan. It is crucial to standardize diet recommendations in an
      evidence-based manner. RECENT FINDINGS: Calorie restriction per se seems
      beneficial regardless of macronutrients composition. However, fat consumption,
      mainly cholesterol and saturated fatty acids are particularly steatogenic. There
      is increasing evidence that fructose, mainly consumed as soft drinks, is highly
      deleterious to the liver. Controversial results regarding modest alcohol
      consumption, suggest that although alcohol should not be advised, it should not
      be strictly forbidden. Recent studies suggest beneficial effects of coffee and
      tea in NAFLD. SUMMARY: Patients with NAFLD should have an individualized diet
      recommendation, in order to lose at least 7% of their weight if overweight,
      reducing caloric intake, mainly at cost of cholesterol and saturated fatty acids.
      Simple sugars should be avoided, and soft drinks discouraged.

PMID- 22878241
TI  - Nourishing the dysfunctional gut and whey protein.
AB  - PURPOSE OF REVIEW: This review discusses the mechanisms of the dysfunctional gut
      during the critical illness and the possibility that an immunonutrient such as
      whey protein can play a role in better tolerance of enteral nutrition, also
      decreasing inflammation and increasing anti-inflammatory defenses. RECENT
      FINDINGS: Impaired gastric motor function and associated feed intolerance are
      common issues in critically ill patients. Some studies have been published with
      enteral nutrition enriched with whey protein as a dietary protein supplement that
      provides antimicrobial activity, immune modulation, improving muscle strength and
      body composition, and preventing cardiovascular disease and osteoporosis.
      SUMMARY: Early enteral feeding will enhance patient recovery and the use of
      enteral diets enriched with whey protein may play a role in these patients.

PMID- 22878242
TI  - Perioperative immunonutrition and gut function.
AB  - PURPOSE OF REVIEW: In the last year, several meta-analyses focused on the
      potential clinical benefits of perioperative immunonutrition in surgical
      patients. Purpose of this review is to summarize their results and to draw
      recommendations about the current indication of immunonutrition in surgery.
      RECENT FINDINGS: Standard enteral preparations have been modified by adding
      specific nutrients, such as arginine, omega-3 fatty acids and others, which have
      been shown to upregulate immune response, to control inflammatory response, and
      to improve gut function after surgery. The majority of the randomized trials
      found that perioperative immunonutrition improved short-term outcome in patients,
      who underwent elective major gastrointestinal (GI) surgery. Four meta-analyses
      including a large number of randomized clinical trials reported that
      perioperative immunonutrition is associated with a substantial reduction in both
      infection rate and length of hospital stay. These results have been found in both
      upper and lower GI patients, regardless of their baseline nutritional status.
      Promising results have been found also in head and neck surgery. SUMMARY: In the
      light of these findings the use of perioperative immunonutrition should be
      implemented in patients undergoing elective major GI surgery. This should result
      in a considerable reduction in both postoperative morbidity and costs for
      healthcare systems.Larger trials are required before recommending immunonutrition
      as a routine practice in head and neck surgery.

PMID- 22878243
TI  - Reliability of symptom analysis during carbohydrate hydrogen-breath tests.
AB  - PURPOSE OF REVIEW: Relevance of symptom analysis during hydrogen breath test
      (HBT) for establishing a clinical diagnosis of sugar intolerance is reviewed.
      RECENT FINDINGS: Evaluation of symptoms developed in response to the ingestion of
      50 g lactose could represent a simple screening test to select patients for
      lactose intolerance testing. Patients who do not develop symptoms do not need to
      be referred for HBT. In addition, symptoms reported by patients during a negative
      HBT cannot be at all times attributed to a false-negative test; instead, a
      'nocebo' effect is likely to be implicated. On the other hand, in a double-blind
      randomized study, a dose of 25 g fructose was suggested as the most appropriate
      for testing individuals with suspected fructose malabsorption, whereas symptom
      reliability to diagnose fructose intolerance was inaccurate. SUMMARY: Whereas the
      development of symptoms after a positive HBT may indicate sugar intolerance, it
      is still not clear whether the absence of symptoms after sugar malabsorption
      gives any indication as to the role of that sugar in the genesis of patient's
      complaints. Further studies should evaluate whether the disappearance of symptoms
      with a sugar-restricted diet after a positive HBT is a better diagnostic
      criterion of sugar intolerance than the development of symptoms.

PMID- 22878244
TI  - Is a gluten-free diet necessary in Marsh I intestinal lesions in patients with
      HLADQ2, DQ8 genotype and without gastrointestinal symptoms?
AB  - PURPOSE OF REVIEW: To describe whether a gluten-free diet (GFD) is indicated in
      Marsh I gluten-sensitive enteropathy where gastrointestinal symptoms are not
      present. Arguments are provided to prescribe a GFD to manage extraintestinal
      symptoms. By contrast, there are not enough reasons to prescribe a GFD to prevent
      long-term complications. RECENT FINDINGS: Population-based and prospective
      observational studies have found that lymphocytic duodenosis may be due to not
      just gluten-sensitive enteropathy but also due to other aetiologic factors. Marsh
      I type lesions may be the cause of iron-deficiency anaemia of unknown aetiology
      which is reverted by a GFD. A similar effect seems to occur with bone
      mineralization and hypertransaminasemia. The beneficial influence of a GFD
      reducing lymphoma and coeliac disease-related mortality remains controversial.
      SUMMARY: An appropriate differential diagnosis of the lymphocytic duodenosis is
      essential before a GFD is indicated. As a third of patients remained undiagnosed,
      in spite of genetic study and specific coeliac serology, flow cytometry and
      transglutaminase antibodies in duodenal tissue may be helpful in establishing
      gluten-sensitive enteropathy diagnosis. Future studies should assess whether
      lymphoma risk is reduced by a GFD in Marsh I patients. Also a more precise
      benefit in bone mineralization in this setting is needed.

PMID- 22878245
TI  - Current world literature.

PMID- 22878247
TI  - Multidrug-resistant Vibrio cholerae O1 in Belgaum, south India.
AB  - An outbreak of acute diarrhoea occurred in the Belgundi area (population 3896) of
      Belgaum Taluka (population 815 581) in Karnataka, South India, in June 2010. An
      estimated 16.22 % of people were affected and 0.16 % deaths were reported. Vibrio
      cholerae O1 El Tor was isolated from 18 of the 147 stool samples cultured. Seven
      out of eight drinking water samples collected from different sources were found
      to be grossly contaminated with faecal coliforms. All isolates were multidrug
      resistant, with some showing resistance to quinolones, gentamicin and
      cephalosporins in addition to co-trimoxazole and tetracycline, the drugs that
      were being used by the state health authorities for empirical treatment. Two
      serotypes and at least eight genotypes of V. cholerae were observed among the
      isolates. Cholera was confirmed as one, if not the only, cause of the outbreak,
      which, to our belief, is the first report of cholera from this region. It might
      have occurred due to a 'flare up' in the number of endemic strains triggered by
      shortage of portable water, onset of monsoon rains and breakdown of sanitation
      systems, rather than being a de novo outbreak arising out of new exogenous
      infectious sources. A change in the empirical treatment, coupled with
      chlorination, improvement in sanitation measures and extensive Information
      Education Communication activities, resulted in decline of the outbreak and
      prevention of further deaths.

PMID- 22878248
TI  - Microbial ecology of the lower genital tract in women with sexually transmitted
      diseases.
AB  - Sexually transmitted diseases (STDs) in women are of great concern to all health
      care providers since many of them are preventable and/or treatable conditions
      which, if left untreated, could have serious sequelae such as pelvic inflammatory
      disease, infertility, cervical cancer, systemic disease, etc. They may also
      become a major public health problem when dealing with diseases such as
      hepatitis, etc., or in people with human immunodeficiency virus. We present here
      a comprehensive review of the common causes of STDs and their treatment.

PMID- 22878249
TI  - Cerebral vasculitis and Cardiobacterium valvarum endocarditis.
AB  - We present a case of aortic and tricuspid native valve endocarditis in which
      Cardiobacterium valvarum was isolated from the blood culture of a 65-year-old
      man. Cardiobacterium valvarum is a fastidious, Gram-negative bacillus. The genus
      Cardiobacterium encompasses two species - Cardiobacterium valvarum and
      Cardiobacterium hominis. Although both species rarely feature as the aetiological
      agent of endocarditis, Cardiobacterium hominis has a higher incidence than
      Cardiobacterium valvarum. For this causative organism, we believe this is the
      first report of fatality prior to surgical intervention and the first clinical
      course to be complicated by cerebral vasculitis. Native valve endocarditis caused
      by Gram-negative bacilli is extremely rare and identification of isolates may
      require the use of reference laboratories with molecular identification
      techniques.

PMID- 22878250
TI  - A mixed infection of Leuconostoc lactis and vancomycin-resistant Enterococcus in
      a liver transplant recipient.
AB  - Bacterial infection in patients who have undergone liver transplantation is a
      major complication of the procedure. Leuconostoc spp. are important pathogenic
      bacteria in individuals with poor immune function, especially transplant
      patients. In this report, we describe the case of a 45-year-old Asian male liver
      transplant recipient who was initially preliminarily diagnosed with infection
      with Leuconostoc pseudomesenteroides by using the microbial tests of the VITEK 2
      system and the aesculin hydrolysis test, and with vancomycin-resistant
      Enterococcus. Subsequently, the Leuconostoc isolate was identified as Leuconostoc
      lactis by 16S rRNA gene partial sequencing. In this paper, we discuss our
      identification of L. lactis based on physiological characteristics and molecular
      methodology. Accurate identification of these infections is important for the
      outcome; use of 16S rRNA gene sequence analysis offers a rapid and precise
      diagnostic approach. Administration of the drug linezolid may be useful for the
      treatment of both Leuconostoc spp. and vancomycin-resistant Enterococcus
      infections. We suggest that clinical analysts should use molecular methods in
      addition to biochemical tests in order to identify Leuconostoc at the species
      level more accurately.

PMID- 22878251
TI  - Detection of mutations in the gyrA and parC genes in Escherichia coli isolates
      carrying plasmid-mediated quinolone resistance genes from diseased food-producing
      animals.
AB  - In this study, the prevalence of plasmid-mediated quinolone resistance (PMQR) was
      investigated in 495 Escherichia coli isolates from diseased food-producing
      animals in Guangdong province, China. The quinolone resistance-determining
      regions (QRDRs) of the gyrA and parC genes were analysed for mutations in 55
      isolates harbouring only oqxAB and all isolates harbouring other PMQR genes.
      Overall, 282 (57.0 %) E. coli isolates had at least one PMQR gene. oqxAB was
      detected in 215 isolates and predominated the PMQR genes, followed by qnrS (63
      isolates), aac(6')-Ib-cr (56 isolates), qnrB (39 isolates) and qepA (18
      isolates). qnrA, qnrC and qnrD were not found in any of the isolates. The rates
      of resistance to ciprofloxacin, enrofloxacin, levofloxacin and nalidixic acid
      were 75.2, 81.0, 70.5 and 97.4 %, respectively, among the 495 isolates. Eight
      types of mutation in gyrA were detected in 154 PMQR-positive isolates, and 147
      isolates were found to have mutations in parC. PFGE analysis indicated that the
      PMQR-positive E. coli isolates were genetically diverse. This study demonstrated
      that the number of mutations in QRDRs of gyrA and/or parC was significantly
      associated with the MICs of quinolones (P<0.01). The rates of resistance to
      ciprofloxacin, enrofloxacin and nalidixic acid in PMQR-positive isolates were
      significantly higher than those in PMQR-negative isolates (P<0.05). In addition,
      the prevalence of oqxAB had significant Spearman correlation coefficients in
      relation to the MICs of all four tested quinolones (P<0.01).

PMID- 22878252
TI  - Development and validation of a multiplex TaqMan real-time PCR for rapid
      detection of genes encoding four types of class D carbapenemase in Acinetobacter
      baumannii.
AB  - A multiplex TaqMan real-time PCR to detect carbapenem-hydrolysing class D beta
      lactamases (bla(OXA-23)-like, bla(OXA-24/40)-like, bla(OXA-51)-like and bla(OXA
      58)-like genes) was developed and evaluated for early detection of imipenem (IMP)
      resistance in clinically significant Acinetobacter baumannii isolates. Well
      characterized strains of A. baumannii were used as positive controls and non
      Acinetobacter strains were used to assess specificity. Analytical sensitivity was
      quantified by comparison with the number of bacterial c.f.u. Forty of 46 (87 %)
      clinically significant and IMP-resistant A. baumannii isolates were positive for
      the bla(OXA-23)-like gene, and one isolate (2 %) was positive for the bla(OXA-58)
      like gene. The bla(OXA-24/40)-like gene was not detected in any of the 46 IMP
      resistant strains and the bla(OXA-51)-like gene was identified in both IMP
      resistant and non-resistant A. baumannii. All 11 non-Acinetobacter bacteria
      produced a negative result for each of the four bla(OXA) genes. This assay was
      able to detect as few as 10 c.f.u. per assay. This real-time PCR method
      demonstrated rapid detection of OXA-like carbapenem resistance in A. baumannii in
      comparison with phenotypic susceptibility testing methodology. This method could
      be adapted to a multiplexed single reaction for rapid detection of genes
      associated with carbapenem resistance in A. baumannii and potentially other
      clinically significant multidrug-resistant Gram-negative bacteria.

PMID- 22878253
TI  - The phylum Synergistetes in gingivitis and necrotizing ulcerative gingivitis.
AB  - The clinical manifestation of necrotizing ulcerative gingivitis (NUG) is distinct
      from that of common gingivitis in that it is characterized by local necrosis of
      the gingival tissues, rapid onset, pain and extensive bleeding. The phylum
      Synergistetes is a novel bacterial phylum consisting of Gram-negative anaerobes,
      with evidence of presence in biofilms associated with periodontal and endodontic
      infections. To date, the involvement of members of this phylum in NUG has not
      been investigated. This study aimed to evaluate the presence and levels of known
      human oral Synergistetes bacterial clusters in dental plaque from patients with
      NUG and compare them with those found in gingivitis. Marginal dental plaque
      samples from 21 NUG and 21 gingivitis patients were analysed quantitatively by
      fluorescent in situ hybridization and microscopy for members of two oral
      Synergistetes clusters (A and B) and for Jonquetella anthropi. Synergistetes
      cluster A bacteria were detected in all samples but at higher levels (9.4-fold)
      and proportions (2.5-fold) in NUG patients than in gingivitis patients. However,
      with regard to Synergistetes cluster B bacteria, there were no differences
      between NUG and gingivitis patients. J. anthropi was detected in only half of the
      samples and at lower levels than the other taxa. In conclusion, these data
      demonstrate that Synergistetes cluster A bacteria, but not cluster B bacteria or
      J. anthropi, are more strongly associated with NUG than with gingivitis.

PMID- 22878254
TI  - Role of TARP interaction in S-SCAM-mediated regulation of AMPA receptors.
AB  - Scaffolding proteins are involved in the incorporation, anchoring, maintenance,
      and removal of AMPA receptors (AMPARs) at synapses, either through a direct
      interaction with AMPARs or via indirect association through auxiliary subunits of
      transmembrane AMPAR regulatory proteins (TARPs). Synaptic scaffolding molecule (S
      SCAM) is a newly characterized member of the scaffolding proteins critical for
      the regulation and maintenance of AMPAR levels at synapses, and directly binds to
      TARPs through a PDZ interaction. However, the functional significance of S-SCAM
      TARP interaction in the regulation of AMPARs has not been tested. Here we show
      that overexpression of the C-terminal peptide of TARP-gamma2 fused to EGFP
      abolished the S-SCAM-mediated enhancement of surface GluA2 expression.
      Conversely, the deletion of the PDZ-5 domain of S-SCAM that binds TARPs greatly
      attenuated the S-SCAM-induced increase of surface GluA2 expression. In contrast,
      the deletion of the guanylate kinase domain of S-SCAM did not show a significant
      effect on the regulation of AMPARs. Together, these results suggest that S-SCAM
      is regulating AMPARs through TARPs.

PMID- 22878255
TI  - Pregnancy and renal outcomes in lupus nephritis: an update and guide to
      management.
AB  - Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age,
      and advances in treatment have resulted in an increasing number of women with
      renal involvement becoming pregnant. Knowledge of the relationship of the
      condition with respect to fertility and pregnancy is important for all clinicians
      involved in the care of women with lupus nephritis because they have complicated
      pregnancies. Presentation of lupus nephritis can range from mild asymptomatic
      proteinuria to rapidly progressive renal failure and may occur before, during, or
      after pregnancy. The timing of diagnosis may influence pregnancy outcome.
      Pregnancy may also affect the course of lupus nephritis. All pregnancies in women
      with lupus nephritis should be planned, preferably after more than six-months of
      quiescent disease. Predictors of poor obstetric outcome include active disease at
      conception or early pregnancy, baseline poor renal function with Creatinine >100
      MUmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid
      syndrome and hypertension. In this review the most recent studies of pregnancies
      in women with lupus nephritis are discussed and a practical approach to managing
      women prepregnancy, during pregnancy and post-partum is described.

PMID- 22878256
TI  - Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus
      erythematosus--a possible link to venous thrombosis?
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased
      risk of developing vascular diseases (VD) such as myocardial infarction, stroke
      and venous thrombosis, which can only partly be explained by traditional risk
      factors. The role of platelets in this process has not been extensively studied.
      Platelet activation supports complement binding to the platelet surface, and
      increased C4d has been seen on platelets in SLE patients as well as in non
      rheumatic patients with stroke. In this study we investigated in vivo platelet
      deposition of the classical complement pathway components C1q, C4d and C3d in
      relation to VD in SLE patients. Furthermore, the ability of serum to support in
      vitro complement deposition on fixed heterologous platelets was analyzed.
      METHODS: Blood from 69 SLE patients and age- and sex-matched healthy individuals
      was collected in sodium-citrate tubes and platelets isolated by centrifugation.
      Complement deposition on platelets was detected by flow cytometry. RESULTS: We
      could demonstrate that SLE patients had increased C1q, C3d and C4d deposition on
      platelets as compared to healthy controls (p < 0.0001). SLE patients with a
      history of venous thrombosis had increased complement deposition on platelets as
      compared to SLE patients without this manifestation (p < 0.05). In vitro studies
      demonstrated that serum from patients with lupus anticoagulant, venous thrombosis
      or antiphospholipid antibody syndrome supported increased platelet C4d deposition
      in vitro as compared to SLE patients without these manifestations (p < 0.05). Our
      data support the hypothesis that platelet activation and the subsequent
      complement deposition on platelets are central in the development of venous
      thrombosis in SLE. CONCLUSIONS: Altogether we suggest that complement deposition
      on platelets could reflect important pathogenetic events related to the
      development of venous thrombosis in SLE and might be used as a marker for venous
      thrombosis in SLE.

PMID- 22878257
TI  - Effectiveness of an injury prevention programme for adult male amateur soccer
      players: a cluster-randomised controlled trial.
AB  - BACKGROUND: The incidence rate of soccer injuries is among the highest in sports,
      particularly for adult male soccer players. PURPOSE: To investigate the effect of
      the 'The11' injury prevention programme on injury incidence and injury severity
      in adult male amateur soccer players. STUDY DESIGN: Cluster-randomised controlled
      trial. METHODS: Teams from two high-level amateur soccer competitions were
      randomly assigned to an intervention (n=11 teams, 223 players) or control group
      (n=12 teams, 233 players). The intervention group was instructed to perform The11
      in each practice session during one soccer season. The11 focuses on core
      stability, eccentric training of thigh muscles, proprioceptive training, dynamic
      stabilisation and plyometrics with straight leg alignment. All participants of
      the control group continued their practice sessions as usual. RESULTS: In total,
      427 injuries were recorded, affecting 274 of 456 players (60.1%). Compliance with
      the intervention programme was good (team compliance=73%, player compliance=71%).
      Contrary to the hypothesis, injury incidences were almost equal between the two
      study groups: 9.6 per 1000 sports hours (8.4-11.0) for the intervention group and
      9.7 (8.5-11.1) for the control group. No significant differences were found in
      injury severity, but a significant difference was observed in the location of the
      injuries: players in the intervention group sustained significantly less knee
      injuries. CONCLUSIONS: This study did not find significant differences in the
      overall injury incidence or injury severity between the intervention and control
      group of adult male soccer players. More research is recommended, focusing on
      injury aetiology and risk factors in adult male amateur soccer players.

PMID- 22878258
TI  - Is hip arthroscopy for femoroacetabular impingement only for athletes?
AB  - PURPOSE: The aim of this study was to compare the outcome of hip arthroscopy for
      femoroacetabular impingement (FAI) between athletes and non-athletes. METHODS:
      The authors prospectively collected data on 122 patients, the largest comparative
      series reported, who underwent hip arthroscopy for FAI. Of these, 80 actively
      participated in sporting activities (athletes), while 42 did not (non-athletes).
      Patients were asked to complete questionnaires for the modified Harris hip score
      (MHHS), non-arthritic hip score (NAHS), patient satisfaction on a visual analogue
      scale (VAS). This was collected immediately before surgery, and at 6 weeks, 6
      months and 1 year after the procedure. The responses to the MHHS questionnaire
      were used to calculate the quality-of-life (QoL) score using the Rosser index
      matrix. RESULTS: A significant improvement in the MHHS, NAHS and QoL was observed
      at 6 weeks, 6 months and 1 year after surgery (p<0.001). The 6-week MHHS (p=0.01)
      and NAHS (p=0.04) for the athletes were significantly better as compared with non
      athletes. However, the 6-month and 1-year MHHS, NAHS and QoL scores were
      statistically similar for both groups. CONCLUSIONS: In this large, prospective
      series of patients we have demonstrated the positive impact of arthroscopic
      surgery for FAI in both the athletic and non-athletic population. Arthroscopic
      management of FAI is thus not the sole domain of the athletic patient. Non
      athletes can do just as well.

PMID- 22878259
TI  - Epidural direct current stimulation over the left medial prefrontal cortex
      facilitates spatial working memory performance in rats.
AB  - BACKGROUND: Extensive evidence supports the notion that modulation of PFC
      excitability using low-intensity electrical stimulation is a promising modality
      for treating neuropsychiatric diseases and improving cognitive function.
      OBJECTIVE: This study examined the effects of epidural direct current stimulation
      (eDCS), a method providing smaller shunting of current and more focal
      stimulation, on spatial working memory. METHODS: Male Wistar rats that were well
      trained in an 8-arm radial maze and in which 5-mm round electrodes were implanted
      over the left medial prefrontal cortex (mPFC) received anodal eDCS (400 MUA
      during 11 min) (n = 9) or sham procedure (n = 9) five minutes before delayed
      tests in the radial maze. RESULTS: Animals that received eDCS over the left mPFC
      had significantly fewer errors in the post-delay performance on the 1-h (P <
      0.01), 4-h (P < 0.001), and 10-h (P < 0.001) delayed tests compared with sham
      treated animals. General locomotor activity was unaffected because time spent in
      each visited arm did not change significantly by eDCS. There was no evidence of
      neuronal lesions in the mPFC underneath the eDCS. CONCLUSIONS: Our results
      suggest that epidural direct current stimulation over the mPFC facilitates
      spatial working memory in rats, an effect that persisted over the long term.

PMID- 22878260
TI  - Osthole attenuates focal inflammatory reaction following permanent middle
      cerebral artery occlusion in rats.
AB  - Osthole, a main active constituent from Cnidium monnieri (L.) CUSSON, has been
      considered therapeutic agent in the treatment of ischemic stroke. This study was
      designed to investigate the effect of osthole on permanent middle cerebral artery
      occlusion (MCAO) in rats. Osthole was administrated by gavage to the normal and
      the MCAO rats. Rats were assessed for neurological deficit after 24 h following
      MCAO, then their brains were evaluated to determine the infarct area, and the
      mRNA and protein levels of some inflammatory factors were detected. It was found
      that MCAO animals pre-treated with osthole for 7 d showed significant improvement
      in all neurological tests compared with vehicle-treated MCAO groups. In addition,
      there was a significant decrease in infarct volume 24 h after occlusion in
      animals pre-treated with osthole versus the vehicle-treated MCAO group. MCAO also
      dramatically caused some inflammatory factors increase. However, pretreatment
      with osthole restored the mRNA and protein levels of these factors, including
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta),
      cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) of ischemic
      penumbra cortices, suggesting that osthole possessed the function of preventing
      brain against ischemic damage, while no significant difference was found in any
      of normal groups with or without osthole. The present study demonstrated that
      osthole may be a novel neuroprotective therapy in the treatment of focal ischemic
      stroke.

PMID- 22878261
TI  - Inhibition of morphine glucuronidation in the liver microsomes of rats and humans
      by monoterpenoid alcohols.
AB  - Morphine is an important drug used to alleviate moderate to severe pain. This
      opiate is mainly metabolized by glucuronidation to a non-analgesic metabolite,
      morphine-3-glucuronide (M-3-G) and an active metabolite morphine-6-glucuronide (M
      6-G). To understand the modulation of morphine glucuronidation activity by
      environmental factors, the effect of endogenous and food-derived compounds on
      morphine uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) in rat and
      human microsomes was evaluated examining the 50% inhibitory concentration
      (IC(50)). The liver microsomes from Sprague-Dawley rats (RLM) and humans (HLM,
      150 donors, pooled microsomes) were used as enzyme sources. Of 27 compounds
      tested, monoterpenoid alcohols, such as borneol and iso-borneol, exhibited a
      strong inhibitory effect on morphine glucuronidation in rat liver microsomes
      (RLM), whereas we failed to detect any inhibitory effect of endogenous substances
      including amino acids and sugars. The substances which have the ability to
      inhibit the activity in RLM are also inhibitory toward morphine glucuronidation
      in HLM and UGT2B7 baculosomes. However, the difference was that while the
      strongest inhibitory effect was observed for iso-menthol in HLM, borneol was the
      strongest inhibitor of the activity mediated by RLM. Although zidovudine is a
      typical substrate of UGT2B7, the inhibition of morphine glucuronidation by
      zidovudine was far weaker than that of monoterpenoid alcohols. These results
      demonstrate that dietary and supplementary monoterpenoid alcohols modify the
      pharmacokinetics and pharmacodynamics of morphine through inhibition of UGT2B7.

PMID- 22878262
TI  - Active surveillance for low-risk prostate cancer.
AB  - Active surveillance (AS) is an important management strategy for men diagnosed
      with low-risk prostate cancer (PCa). The need for AS is increasing due to the
      awareness that many PCa are identified that show a low growth potential and
      therefore are likely to remain clinically asymptomatic during the lifetime of an
      individual. Currently there is no good method to prevent the overdiagnosis of
      indolent cancers upfront. During the last decade, several studies on AS around
      the world have made observations that feed the discussion on how to select and
      monitor these patients, how to proceed with the research to develop a better and
      more precise clinical definition of indolent cancers and how to manage men under
      AS clinically. Furthermore, patients' perspectives have become clearer, and
      quality of life studies give direction to the practical approach and care for
      patients and partners. This paper reflects the consensus on the state of the art
      and the future direction of AS, based on the Inside Track Conference "Active
      Surveillance for low risk prostate cancer" (Chairmen: C.H. Bangma, NL, and L.
      Klotz, CA; Co-Chairmen: L.J. Denis, BE, and C. Parker, UK; Scientific
      Coordinators: M. J. Roobol, NL, and E.W. Steyerberg, NL), organized by the
      European School of Oncology in collaboration with Europa Uomo in Rotterdam, the
      Netherlands in January 2012. Topics for discussion were the optimisation of
      patient selection based on indolent disease definition, the incorporation of
      therapeutic agents into AS programs, the optimisation of patient care, and the
      application of emerging technologies and biomarkers.

PMID- 22878263
TI  - Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic
      signaling pathways.
AB  - The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response
      as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such
      as PHD3, which in turn increases the stability of hypoxia-inducible factor (HIF)
      1alpha. In the present study, we identify the serine/threonine kinase DYRK2 as
      SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16,
      Thr26, Ser28, Ser68, and Thr119). Phosphomimetic and phospho-mutant forms of
      SIAH2 exhibit different subcellular localizations and consequently change in PHD3
      degrading activity. Accordingly, phosphorylated SIAH2 is more active than the
      wild-type E3 ligase and shows an increased ability to trigger the HIF-1alpha
      mediated transcriptional response and angiogenesis. We also found that SIAH2
      knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2
      polyubiquitination and degradation. Hypoxic conditions cause a SIAH2-dependent
      DYRK2 polyubiquitination and degradation which ultimately also results in an
      impaired SIAH2 phosphorylation. Similarly, DYRK2-mediated phosphorylation of p53
      at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism
      underlying chemotherapy resistance in solid tumors.

PMID- 22878266
TI  - Occupational safety and health in Japan: current situations and the future.
AB  - The Industrial Safety and Health Law enacted in 1972 has contributed much to the
      progress of occupational safety and health (OSH) activities. Many indicators
      including death and illness statistics show continued improvement up to date. The
      establishment of OSH organization within enterprises and 5-yr administrative
      programs formulated by the Ministry of Health, Labour, and Welfare (MHLW) were
      important factors for satisfactory management. The past programs indicate that
      the weight of self regulation in comparison to legal control gradually increased
      since late 1990s. In spite of the past achievement, many hazards such as
      overwork, mental stress, chemical agents and others still remain to be prevented.
      The systematic risk assessment of unregulated chemicals by the MHLW proved to be
      an effective scheme for risk-based management and to deserve continued
      implementation. The size of human resources for OSH was estimated at 1.5 million.
      In view of the adverse effect on OSH by economic, social and political
      environment in the future, the importance of the efficiency of OSH management was
      indicated. Since the efficiency depends on the competence of OSH personnel and
      the level of scientific basis, it was concluded that the fundamental policy for
      the future should give high priority to education and research.

PMID- 22878264
TI  - MAPC culture conditions support the derivation of cells with nascent hypoblast
      features from bone marrow and blastocysts.

PMID- 22878265
TI  - Novel double-decker phthalocyaninato terbium(III) single molecule magnets with
      stabilised redox states.
AB  - Double-decker phthalocyanine lanthanide complexes are single molecule magnets
      (SMMs) presenting a thermally activated magnetic relaxation with relatively high
      effective barriers. For this reason they are potential candidates as components
      for data storage and spintronic devices. One of the disadvantages of these
      compounds is their redox instability: they are oxidized or reduced in the
      presence of mild oxidizing and reducing agents. To solve this issue, we designed,
      prepared and characterized new double-decker phthalocyanine based SMMs bearing
      electron withdrawing groups and therefore presenting an increased redox
      stability. In the present article, the synthesis and characterization of these
      novel compounds is presented and we demonstrate how the magnetic behavior of the
      complexes is virtually identical to that of the parent unsubstituted compounds.

PMID- 22878267
TI  - Occupational safety and health in the United kingdom: securing future workplace
      health and wellbeing.
AB  - The industrial revolution that took place in the United Kingdom (UK) between 1760
      and 1830 lead to profound social change, with rapid urbanisation associated with
      squalid living conditions and epidemics of infectious diseases. The next 150 yr
      or so saw the introduction of many specific acts of health and safety
      legislation. In 1974 new overarching primary legislation was introduced that
      would produce a step change in the evolution of health and safety enforcement. In
      2004, a new strategy was launched designed to promote a vision embedding health
      and safety as a cornerstone of a civilised society and to achieve a record of
      workplace health and safety that leads the world. Good progress in controlling
      many safety hazards and improving occupational hygiene has been made. There has
      been a fall in numbers of a wide range of injuries and diseases or illnesses
      since 2000. The challenge will be to maintain these favourable trends and prepare
      for new and emerging diseases at a time when resources are diminishing. The
      importance of occupational health within the UK health and safety strategy has
      been recognised over the last decade. Occupational health is developing a new
      paradigm which combines classical health risk management with assessment of
      workability, rehabilitation back to work and promotion of health and wellbeing.
      There is an increasing recognition that being in supported employment is good for
      health and reduces health inequalities.

PMID- 22878268
TI  - The diagnostic evaluation of patients with potential adult-onset autoinflammatory
      disorders: our experience and review of the literature.
AB  - Hereditary periodic fever syndromes (HPFSs) are a group of inherited disorders of
      the innate immune system caused by mutations of genes involved in the regulation
      or activation of the inflammatory response, which belong to the category of
      autoinflammatory disorders. Most HPFs typically have an onset in pediatric age,
      while a limited number of patients experience disease onset during adulthood. The
      relative rarity and lack of information on adult-onset autoinflammatory diseases
      make it likely that genetic testing is often inconclusive. Recently, we have
      identified a set of variables related to the probability of detecting gene
      mutations in MEFV, responsible for familial Mediterranean fever, and TNFRSF1A,
      responsible for tumor necrosis factor receptor-associated periodic syndrome. In
      addition, we have proposed a diagnostic score for identifying those patients at
      high risk of carrying mutations in these genes. However, before the score can be
      recommended for application, further evaluation by means of longitudinal studies
      on different ethnicities and different populations deriving from other
      geographical areas is needed in order to definitively verify both its sensitivity
      and its specificity. The present manuscript offers our suggestions on how to
      establish a differential diagnosis for adult-onset HPFs, as well as a review of
      the literature, and we also provide a score revision available online.

PMID- 22878269
TI  - Amyloidosis in autoinflammatory syndromes.
AB  - AA amyloidosis may still dramatically impact on the outcome of patients with
      autoinflammatory diseases, particularly when diagnosis is delayed. Clinicians
      should maintain a high level of attention to identify early this severe
      complication. Initial signs mostly reflect kidney damage, with proteinuria, with
      or without renal failure, being the more frequent presenting feature. If SAA
      levels are not rapidly normalized, progression toward end-stage kidney disease
      and dialysis invariably occurs. Over time, multiple organ failure, including
      heart, autonomic and adrenal insufficiency usually complicates the disease
      course. Limited tools are still available to predict the occurrence of AA,
      therefore close monitoring of at risk patients is required to detect promptly the
      "early red flags" through periodic search for preclinical amyloid deposits and
      regular assessment of proteinuria and SAA concentration. Effective control of the
      underlying inflammatory process may halt disease progression and even reverse
      damage. Anti-cytokine agents are becoming the mainstay of therapy to prevent and
      treat AA, including patients with FMF that do not respond or do not tolerate
      adequate colchicine dosages. Renal transplantation can be considered in selected
      patients progressing to end-stage kidney disease. Novel treatments are under
      development, targeting key molecular events in the fibrillogenesis process.

PMID- 22878270
TI  - New genetic interpretation of old diseases.
AB  - The title of this section, "New genetic interpretation of old diseases,"
      perfectly reflects the unique history of our understanding of autoinflammatory
      diseases (AIDs). Indeed, the main clinical feature of most AIDs is the recurrent
      fever, a symptom that has been extensively documented for centuries. However, the
      first clear description of a patient suffering from the AID prototype, familial
      Mediterranean fever (FMF), has only been reported in 1908, although dating
      studies have shown that ancestral mutations appeared in biblical times. FMF and
      11 other AID genes were identified between 1997 and 2011. The patient's care has
      dramatically benefited from the elucidation of the molecular defect underlying
      similar diseases of the innate immune system. However, accumulation of present
      and future sequence data let us anticipate that interpretation of genetic
      diagnosis will be increasingly difficult.

PMID- 22878272
TI  - Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA).
AB  - PFAPA syndrome (acronym of periodic fever, aphthous stomatitis, pharyngitis and
      cervical adenitis) is the most common cause of periodic fever in childhood.
      Nowadays, it is considered part of the wide family of the autoinflammatory
      diseases, but a genetic or molecular marker hasn't been identified yet,
      therefore, its etiology is still unknown. Diagnosis is essentially based on
      clinical criteria but, especially in younger children, it is sometimes difficult
      to differentiate it from other hereditary periodic fever syndromes. Fever attacks
      in PFAPA have a spontaneous resolution and in a high rate of patients the
      syndrome ends spontaneously over time. Treatment is still a matter of debate.
      Usually a single administration of oral corticosteroids aborts attacks.
      Tonsillectomy may be an alternative option but its role remains to be clarified.

PMID- 22878271
TI  - Attempts at suppression of amyloidogenesis in a mouse model by a variety of anti
      inflammatory agents.
AB  - OBJECTIVE: The mainstay of AA amyloidosis prevention and treatment is suppression
      of inflammation. In the present study we have tried to determine the efficacy of
      a variety of anti-inflammatory agents at suppressing AA amyloidosis in a mouse
      model of the disease. METHODS: AA amyloidosis was induced in Swiss male mice
      using amyloid enhancing factor and AgNO(3). Suppression of amyloid formation was
      studied in comparison to saline, using i.p. injections of several non-steroidal
      anti-inflammatory agents, TNF-alpha inhibitors, interferon-alpha, leflunomide and
      a variety of chemotherapeutic agents, commonly used in the treatment of
      inflammatory illnesses such as methotrexate, azathioprine, chlorambucil and
      cyclophosphamide. The degree of splenic amyloid deposition was determined using
      Congo red staining of smears and a 5 grade scale. RESULTS: The alkylating agents,
      chlorambucil and cyclophosphamide, each resulted in a significant 88% reduction
      in amyloid deposition, yielded the most striking effect on amyloidogenesis
      suppression in the enhanced mouse model (p<0.0002). The non-steroidal anti
      inflammatory agents tested varied widely in their ability to suppress amyloid
      formation in our mouse model, but only diflunisal was significantly effective,
      inducing a suppression of 57% (p=0.04). Other chemotherapeutic agents tested,
      methotrexate and azathioprine, yielded 32% and 27% suppression, which fell short
      of statistical significance. Surprisingly, the immunomodulatory agents
      etanercept, infliximab, leflunomide and interferon-alpha had insignificant
      effects on amyloid formation in this model. CONCLUSION: Our findings suggest that
      alkylating agents may have a role in the prevention of amyloidogenesis. Further
      testing of these agents in animal models and in the clinical setting is needed.

PMID- 22878273
TI  - Familial Mediterranean fever: new phenotypes.
AB  - Familial Mediterranean fever (FMF) is an inherited autosomal recessive disorder,
      ethnically restricted and commonly found among individuals of Mediterranean
      descent, caused by MEditerranean FeVer gene (MEFV) mutations on chromosome 16. It
      is the most frequent periodic febrile syndrome among the autoinflammatory
      syndromes. Clinically, FMF can be distinguished into three phenotypes: type 1,
      which is commonly associated with recurrent short episodes of inflammation and
      serositis, including fever, peritonitis, synovitis, pleuritis, but also
      pericarditis, orchitis or meningitis episodes; type 2, characterized by the
      evidence of reactive amyloid-associated (AA) amyloidosis, the most severe
      complication of FMF, as the first clinical manifestation of the disease in an
      otherwise asymptomatic individual; type 3, referred to the 'silent' homozygous or
      compound heterozygote state, in which two MEFV mutations are detected without
      signs or symptoms of FMF nor of AA amyloidosis. In the recent years it has been
      observed that also heterozygous mutation carriers can suffer from a mild or
      incomplete form of FMF, named 'FMF-like' disease. The influence of other
      modifiers genes and/or environmental factors can contribute to the variable
      penetrance and to the phenotypic variability of FMF. The insight into complex
      clinical and genetic cases will provide adjunctive details for the comprehension
      of the mechanisms of this kaleidoscopic disease.

PMID- 22878274
TI  - Autoinflammation and autoimmunity: bridging the divide.
AB  - As soon as autoinflammatory diseases (AIDs) emerged as new entities, they have
      been linked to the well known world of autoimmunity. In fact, AIDs and systemic
      autoimmune diseases (ADs), share some characteristics: they start with the prefix
      "auto" to define a pathological process directed against self; they are systemic
      diseases, frequently involving musculoskeletal system; both include monogenic and
      polygenic diseases. From the pathogenetic point of view, they are characterized
      by a chronic activation of immune system, which eventually leads to tissue
      inflammation in genetically predisposed individuals. Nevertheless, the specific
      effectors of the damage are different in the two groups of diseases: in AIDs the
      innate immune system directly causes tissue inflammation, whereas in ADs the
      innate immune system activates the adaptive immune system which, in turn, is
      responsible for the inflammatory process. Mutations in inflammasome-related
      proteins, particularly in NOD-like receptor (NLR) genes, have been strongly
      associated to the occurrence of AIDs, whereas the link between inflammasome and
      ADs is less clear. However, a role for this multiprotein-complex in some ADs can
      be postulated, since a wide spectrum of endogenous danger signals can activate
      NLRs and inflammasome products, including IL-1beta, can activate adaptive
      immunity. An association between single nucleotide polymorphisms (SNPs) localized
      in the inflammasome gene NLRP1 and systemic lupus erythematosus has recently been
      reported. AIDs and ADs are currently subdivided into two different groups, but
      looking at their similarities they might be considered as a single group of
      diseases with a large immune pathological and clinical spectrum which includes at
      one end pure ADs and at the other end pure AIDs.

PMID- 22878275
TI  - Corrected end-tidal P(CO(2)) accurately estimates Pa(CO(2)) at rest and during
      exercise in morbidly obese adults.
AB  - BACKGROUND: Obesity affects lung function and gas exchange and imposes mechanical
      ventilatory limitations during exercise that could disrupt the predictability of
      Pa(CO(2)) from end-tidal P(CO(2)) (P(ETCO(2))), an important clinical tool for
      assessing gas exchange efficiency during exercise testing. Pa(CO(2)) has been
      estimated during exercise with good accuracy in normal-weight individuals by
      using a correction equation developed by Jones and colleagues (P(JCO(2)) = 5.5 +
      0.9 x P(ETCO(2)) - 2.1 x tidal volume). The purpose of this project was to
      determine the accuracy of Pa(CO(2)) estimations from P(ETCO(2)) and P(JCO(2))
      values at rest and at submaximal and peak exercise in morbidly obese adults.
      METHODS: Pa(CO(2)) and P(ETCO(2)) values from 37 obese adults (22 women, 15 men;
      age, 39 +/- 9 y; BMI, 49 +/- 7; [mean +/- SD]) were evaluated. Subjects underwent
      ramped cardiopulmonary exercise testing to volitional exhaustion. P(ETCO(2)) was
      determined from expired gases simultaneously with temperature-corrected arterial
      blood gases (radial arterial catheter) at rest, every minute during exercise, and
      at peak exercise. Data were analyzed using paired t tests. RESULTS: P(ETCO(2))
      was not significantly different from Pa(CO(2)) at rest (P(ETCO(2)) = 37 +/- 3 mm
      Hg vs Pa(CO(2)) = 38 +/- 3 mm Hg, P = .14). However, during exercise, P(ETCO(2))
      was significantly higher than Pa(CO(2)) (submaximal: 42 +/- 4 vs 40 +/- 3, P <
      .001; peak: 40 +/- 4 vs 37 +/- 4, P < .001, respectively). Jones' equation
      successfully corrected P(ETCO(2)), such that P(JCO(2)) was not significantly
      different from Pa(CO(2)) (submax: P(JCO(2)) = 40 +/- 3, P = .650; peak: 37 +/- 4,
      P = .065). CONCLUSION: P(JCO(2)) provides a better estimate of Pa(CO(2)) than
      P(ETCO(2)) during submaximal exercise and at peak exercise, whereas at rest both
      yield reasonable estimates in morbidly obese individuals. Clinicians and
      physiologists can obtain accurate estimations of Pa(CO(2)) in morbidly obese
      individuals by using P(JCO(2)).

PMID- 22878276
TI  - Onsen (hot springs) in Japan--transforming terrain into healing landscapes.
AB  - Japan is situated on the Pacific fire rim and has a large number of hot springs
      (onsens). There are over 27,000 sources of such springs and the country has a
      well regulated system of onsens. Within this geographical and cultural
      peculiarities certain unique traditional health practices have evolved, prominent
      among which is Touji or onsen therapy. The article highlights various healing
      practices surrounding onsens, institutionalization of these practices, current
      policy regulations, standards and their contemporary challenges. This research
      used publicly available information from literature sources and data through
      expert interviews. It draws attention to the fact that touji has been
      marginalized in the recent health policies. The study highlights that onsen as a
      therapeutic landscape has an important role in maintaining health and wellbeing
      in the country and holds immense value in building social cohesion in local
      communities. The study points to the need for appropriate studies on the social
      and symbolic healing elements related to onsen landscapes, as well as the need
      for developing a comprehensive strategy for strengthening their culturally
      specific health management roles.

PMID- 22878277
TI  - Liquid sensing capability of rolled-up tubular optical microcavities: a
      theoretical study.
AB  - Rolled-up tubular optical microcavities are a novel type of optical sensor for
      identifying different liquids and monitoring single cells. Based on a Mie
      scattering method, we systematically study the optical resonances and liquid
      sensing capability of microtubes. Analytical formulas are presented to calculate
      the resonant wavelengths lambda(r), Q factors, sensitivities S and figures of
      merit QS. Both ideal and rolled-up microtubes are considered for different
      optical materials in tube walls (refractive indices ranging from 1.5 to 2.5) and
      for three setups: tube-in-liquid, hollow-tube-in-liquid and liquid-in-tube. It is
      found that for rolled-up microtubes, the highest QS can be achieved by using the
      liquid-in-tube setup and very thin wall thicknesses. A maximal sensitivity is
      found in the case of the liquid cylinder. Our theory well explains a recent
      experiment under the setup of tube-in-liquid. It is also found that, although it
      describes the case of tube-in-liquid well, the waveguide approximation approach
      is not suitable for the case of liquid-in-tube. The results could be useful to
      design better optofluidic devices based on rolled-up microtubes.

PMID- 22878278
TI  - Global strategy for the diagnosis, management, and prevention of chronic
      obstructive pulmonary disease: GOLD executive summary.
AB  - Chronic obstructive pulmonary disease (COPD) is a global health problem, and
      since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has
      published its strategy document for the diagnosis and management of COPD. This
      executive summary presents the main contents of the second 5-year revision of the
      GOLD document that has implemented some of the vast knowledge about COPD
      accumulated over the last years. Today, GOLD recommends that spirometry is
      required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure
      proper evaluation of severity of airflow limitation. The document highlights that
      the assessment of the patient with COPD should always include assessment of (1)
      symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and
      (4) comorbidities. The first three points can be used to evaluate level of
      symptoms and risk of future exacerbations, and this is done in a way that splits
      patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and
      pharmacologic management of COPD match this assessment in an evidence-based
      attempt to relieve symptoms and reduce risk of exacerbations. Identification and
      treatment of comorbidities must have high priority, and a separate section in the
      document addresses management of comorbidities as well as COPD in the presence of
      comorbidities. The revised document also contains a new section on exacerbations
      of COPD. The GOLD initiative will continue to bring COPD to the attention of all
      relevant shareholders and will hopefully inspire future national and local
      guidelines on the management of COPD.

PMID- 22878280
TI  - Class A scavenger receptor deficiency exacerbates lung tumorigenesis by
      cultivating a procarcinogenic microenvironment in humans and mice.
AB  - RATIONALE: Genetic alterations on 8p22 have been implicated in multiple cancers,
      including lung cancer. In this region, genetic variants of the class A scavenger
      receptor (SR-A) gene have been associated with prostate cancer risk and have been
      highlighted as a potential susceptibility gene of cancer. OBJECTIVES: To
      determine whether common polymorphisms in the SR-A gene are associated with human
      lung cancer risk and to clarify the role of SR-A in lung carcinogenesis. METHODS:
      The relationship of three potentially functional polymorphisms (T-365C, T+25C,
      and Ala275Pro) in the SR-A gene with lung cancer risk was evaluated in 1287 lung
      cancer case subjects and 1261 control subjects from the Chinese population. At
      the same time, SR-A null mice were used to investigate its role in lung cancer
      development. MEASUREMENTS AND MAIN RESULTS: The T+25C polymorphism was
      independently associated with lung cancer risk and significantly correlated with
      decreased expression of SR-A. The decreased SR-A expression was also found in
      tumor tissues as compared with normal tissues. Depletion of SR-A boosted the
      growth and angiogenesis of implanted Lewis lung carcinoma in mice. The cancer
      suppressing capability of SR-A was attributable to its expression in bone marrow
      derived cells as evidenced by bone marrow transplantation. Further analysis
      revealed augmented expression of proangiogenic factors including matrix
      metalloproteinase-9 (MMP9) in SR-A-deficient mice, indicative of a more
      procarcinogenic microenvironment. Last, zoledronate, an MMP9 inhibitor, abrogated
      acceleration of tumor growth conferred by SR-A loss-of-function. CONCLUSIONS:
      Evidence from the population study and mouse model strongly indicates that SR-A
      may function as a tumor modulator to inhibit lung cancer growth through affecting
      the tumor microenvironment.

PMID- 22878281
TI  - Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense
      infection and inducible resistance.
AB  - RATIONALE: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are
      frequently the only oral antibiotics that are active against Mycobacterium
      abscessus and M. massiliense infections. OBJECTIVES: To compare the activity of
      CLR and AZM in experimental models. METHODS: We compared the treatment efficacies
      of CLR and AZM and determined the correlation between efficacy and induced
      erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental
      models of M. abscessus and M. massiliense infections. MEASUREMENTS AND MAIN
      RESULTS: In all tested M. abscessus isolates, a high level of inducible CLR
      resistance developed (minimal inhibitory concentration [MIC] on Day 3 versus Day
      14; P < 0.001). Whereas the AZM MIC increased on Day 14 (P < 0.01 versus Day 3),
      the level was significantly lower than the CLR MIC on Day 14 (P < 0.001).
      However, the MICs of CLR and AZM for the M. massiliense isolates did not change.
      Compared with CLR, AZM presented greater antibiotic activity against M. abscessus
      in vitro, ex vivo, and in vivo (P < 0.05), whereas both macrolides were
      comparably effective against M. massiliense. In M. abscessus infection, the level
      of erm(41) expression was higher after exposure to CLR than after exposure to AZM
      (P < 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M.
      massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41)
      was responsible for inducible CLR resistance. CONCLUSIONS: CLR induces greater
      erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus
      infection. AZM may be more effective against M. abscessus, whereas both
      macrolides appear to be equally effective against M. massiliense.

PMID- 22878283
TI  - If only it was as simple as bugs.

PMID- 22878282
TI  - Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung
      disease.
AB  - RATIONALE: Little is known regarding the application of therapeutic drug
      monitoring for treatment of Mycobacterium avium complex (MAC) lung disease.
      OBJECTIVES: To evaluate drug interactions of multidrug regimens and clinical
      usefulness of therapeutic drug monitoring in the management of MAC lung disease.
      METHODS: A total of 130 patients with MAC lung disease and 60 patients with
      Mycobacterium abscessus complex lung disease were enrolled in this study. All of
      the MAC patients were treated with multidrug regimens that included
      clarithromycin (CLR), rifampin (RIF) or rifabutin (RFB), and ethambutol (EMB),
      and the plasma drug concentrations of CLR, RIF, and EMB were measured.
      MEASUREMENTS AND MAIN RESULTS: Peak plasma CLR concentrations were lower in
      patients with MAC lung disease who received daily (median, 0.3 MUg/ml) or
      intermittent (median, 0.2 MUg/ml) therapy with CLR in conjunction with RIF in
      both groups, compared with those diagnosed with M. abscessus complex lung disease
      who received CLR without RIF (median, 3.8 MUg/ml; P < 0.05). The proportion of
      patients with MAC lung disease who received daily therapy and whose plasma CLR
      levels were below the target range of 2 MUg/ml was 97% (96 of 99), and this rate
      was 100% (21 of 21) among patients with MAC lung disease who received
      intermittent therapy. The peak plasma drug concentrations and the peak plasma
      drug concentration/minimal inhibitory concentration ratios of CLR, RIF, and EMB
      did not differ between patients with unfavorable treatment outcomes and those
      with favorable outcomes. CONCLUSIONS: Low plasma CLR concentrations were common
      in patients treated for MAC lung disease. However, there was no association
      between low plasma CLR concentrations and treatment outcomes. Therefore,
      therapeutic drug monitoring may not be beneficial in managing the therapy of
      patients with MAC lung disease.

PMID- 22878284
TI  - Relies on experience.

PMID- 22878285
TI  - Outwith utopia.

PMID- 22878286
TI  - Much to commend.

PMID- 22878287
TI  - New anticoagulants.

PMID- 22878288
TI  - Aspire to prevention.

PMID- 22878289
TI  - Down to the wire.

PMID- 22878296
TI  - What are your views on caries?

PMID- 22878302
TI  - Is seaweed superior to toothpaste?

PMID- 22878305
TI  - Child dental neglect: is it a neglected area in the UK?
AB  - This commentary focuses on the condition of dental neglect (DN) in children in
      the UK. It is divided into three sections: the first section defines DN in
      children and its consequences, the second section discusses who may be
      responsible for dental diseases in children as a result of neglect and the third
      section proposes a holistic approach to address DN in children in the UK.

PMID- 22878306
TI  - Want to do clinical research? Changes in the NHS mean there's never been a better
      time.
AB  - This article aims to explain the recent changes in the NHS research support
      system as it applies to dentistry; information that will be of value to all
      clinical academics and dentists considering taking part in research. The changes
      mean that investment goes where patient benefit research is happening. The system
      has put in place transparent mechanisms to reimburse NHS organisations including
      dental practices that take part in research and train clinicians in research
      skills. Through NHS investment in 'translational research', public funds are used
      directly to deliver improved and more cost effective patient care.

PMID- 22878279
TI  - Weight gain after lung reduction surgery is related to improved lung function and
      ventilatory efficiency.
AB  - RATIONALE: Lung volume reduction surgery (LVRS) is associated with weight gain in
      some patients, but the group that gains weight after LVRS and the mechanisms
      underlying this phenomenon have not been well characterized. OBJECTIVES: To
      describe the weight change profiles of LVRS patients enrolled in the National
      Emphysema Treatment Trial (NETT) and to correlate alterations in lung
      physiological parameters with changes in weight. METHODS: We divided 1,077 non
      high-risk patients in the NETT into groups according to baseline body mass index
      (BMI): underweight (<21 kg/m(2)), normal weight (21-25 kg/m(2)), overweight (25
      30 kg/m(2)), and obese (>30 kg/m(2)). We compared BMI groups and LVRS and medical
      groups within each BMI stratum with respect to baseline characteristics and
      percent change in BMI (%DeltaBMI) from baseline. We examined patients with
      (DeltaBMI >= 5%) and without (DeltaBMI < 5%) significant weight gain at 6 months
      and assessed changes in lung function and ventilatory efficiency (Ve/Vco(2)).
      MEASUREMENTS AND MAIN RESULTS: The percent change in BMI was greater in the LVRS
      arm than in the medical arm in the underweight and normal weight groups at all
      follow-up time points, and at 12 and 24 months in the overweight group. In the
      LVRS group, patients with DeltaBMI >= 5% at 6 months had greater improvements in
      FEV(1) (11.53 +/- 9.31 vs. 6.58 +/- 8.68%; P < 0.0001), FVC (17.51 +/- 15.20 vs.
      7.55 +/- 14.88%; P < 0.0001), residual volume (-66.20 +/- 40.26 vs. -47.06 +/-
      39.87%; P < 0.0001), 6-minute walk distance (38.70 +/- 69.57 vs. 7.57 +/- 73.37
      m; P < 0.0001), maximal expiratory pressures (12.73 +/- 49.08 vs. 3.54 +/- 32.22;
      P = 0.0205), and Ve/Vco(2) (-1.58 +/- 6.20 vs. 0.22 +/- 8.20; P = 0.0306) at 6
      months than patients with DeltaBMI < 5% at 6 months. CONCLUSIONS: LVRS leads to
      weight gain in nonobese patients, which is associated with improvement in lung
      function, exercise capacity, respiratory muscle strength, and ventilatory
      efficiency. These physiological changes may be partially responsible for weight
      gain in patients who undergo LVRS.

PMID- 22878307
TI  - Oral diagnosis and treatment planning: part 3. Periodontal disease and assessment
      of risk.
AB  - Periodontal diseases are diagnosed on the basis of clinical signs, with
      radiographs assisting in treatment planning decisions and in the delivery of
      periodontal care. In the first instance, use of a screening system, to screen out
      patients with minimal or no disease, and to screen in those with disease
      requiring full diagnosis and treatment planning for periodontitis, is a very
      helpful approach. The full diagnostic approach relies on periodontal probing and
      the response to probing. Periodontal probing depth measurements and periodontal
      attachment level registrations are recordings of clinical findings, which depend
      upon the state of health of the periodontal tissues to a large extent.

PMID- 22878308
TI  - Titanium alloy removable partial denture framework in a patient with a metal
      allergy: a case study.
AB  - This article describes a mandibular bilateral free-end saddle case in a 63-year
      old female with a metal allergy. Conventional denture alloys are contraindicated
      and acrylic mucosa-borne dentures were not tolerated. The use of a titanium alloy
      framework is shown to be a successful alternative in this case.

PMID- 22878313
TI  - Summary of: patient safety in dentistry - state of play as revealed by a national
      database of errors.
AB  - INTRODUCTION: Modern dentistry has become increasingly invasive and
      sophisticated. Consequently the risk to the patient has increased. The aim of
      this study is to investigate the types of patient safety incidents (PSIs) that
      occur in dentistry and the accuracy of the National Patient Safety Agency (NPSA)
      database in identifying those attributed to dentistry. METHODS: The database was
      analysed for all incidents of iatrogenic harm in the speciality of dentistry. A
      snapshot view using the timeframe January to December 2009 was used. The free
      text elements from the database were analysed thematically and reclassified
      according to the nature of the PSI. Descriptive statistics were provided.
      RESULTS: Two thousand and twelve incident reports were analysed and organised
      into ten categories. The commonest was due to clerical errors - 36%. Five areas
      of PSI were further analysed: injury (10%), medical emergency (6%),
      inhalation/ingestion (4%), adverse reaction (4%) and wrong site extraction (2%).
      DISCUSSION: There is generally low reporting of PSIs within the dental
      specialities. This may be attributed to the voluntary nature of reporting and the
      reluctance of dental practitioners to disclose incidences for fear of loss of
      earnings. A significant amount of iatrogenic harm occurs not during treatment but
      through controllable pre- and post-procedural checks. CONCLUSION: Incidences of
      iatrogenic harm to dental patients do occur but their reporting is not widely
      used. The use of a dental specific reporting system would aid in minimising
      iatrogenic harm and adhere to the Care Quality Commission (CQC) compliance
      monitoring system on essential standards of quality and safety in dental
      practices.

PMID- 22878314
TI  - Summary of: evaluation of the basic erosive wear examination (BEWE) for use in
      general dental practice.
AB  - OBJECTIVE: The basic erosive wear examination (BEWE) is a relatively new index
      proposed for the screening and recording of tooth wear in adults. The aim of this
      study was to test the validity and reliability of the BEWE. DESIGN: Cross
      sectional study of a sample of 164 adult patients. SETTING: General dental
      practice in East Lancashire, UK in 2010.Subjects Patients attending for routine
      examination or treatment. MAIN OUTCOME MEASURES: By screening patients with the
      BEWE and comparing the results to the established tooth wear index (TWI) the
      sensitivity and specificity of the BEWE was established. RESULTS: The BEWE
      predicted moderate to severe wear (BEWE grade 3) with a sensitivity of 48.6% and
      a specificity of 96.1%, and predicted severe wear with a sensitivity of 90.9% and
      a specificity of 91.5% (also BEWE score 3). Inter- and intra-examiner reliability
      for the BEWE were both moderate (kappa(w) = 0.43 and 0.57 respectively).
      CONCLUSION(S): BEWE scores show a similar distribution to TWI scores and the
      examination is an effective screening test for severe tooth wear. The moderate
      levels of examiner reliability suggests the BEWE scores should be interpreted
      with some caution.

PMID- 22878332
TI  - Jenny Harris: 'we have been guilty of neglecting dental neglect', an interview by
      Ruth Doherty.
AB  - Whilst at this year's British Dental Conference and Exhibition in Manchester,
      paediatric dentistry consultant, Jenny Harris spoke to the BDJ about neglecting
      dental neglect, managing paediatric patients and the GDP's role in child
      protection.

PMID- 22878337
TI  - Patient safety in dentistry - state of play as revealed by a national database of
      errors.
AB  - INTRODUCTION: Modern dentistry has become increasingly invasive and
      sophisticated. Consequently the risk to the patient has increased. The aim of
      this study is to investigate the types of patient safety incidents (PSIs) that
      occur in dentistry and the accuracy of the National Patient Safety Agency (NPSA)
      database in identifying those attributed to dentistry. METHODS: The database was
      analysed for all incidents of iatrogenic harm in the speciality of dentistry. A
      snapshot view using the timeframe January to December 2009 was used. The free
      text elements from the database were analysed thematically and reclassified
      according to the nature of the PSI. Descriptive statistics were provided.
      RESULTS: Two thousand and twelve incident reports were analysed and organised
      into ten categories. The commonest was due to clerical errors - 36%. Five areas
      of PSI were further analysed: injury (10%), medical emergency (6%),
      inhalation/ingestion (4%), adverse reaction (4%) and wrong site extraction (2%).
      DISCUSSION: There is generally low reporting of PSIs within the dental
      specialities. This may be attributed to the voluntary nature of reporting and the
      reluctance of dental practitioners to disclose incidences for fear of loss of
      earnings. A significant amount of iatrogenic harm occurs not during treatment but
      through controllable pre- and post-procedural checks. CONCLUSION: Incidences of
      iatrogenic harm to dental patients do occur but their reporting is not widely
      used. The use of a dental specific reporting system would aid in minimising
      iatrogenic harm and adhere to the Care Quality Commission (CQC) compliance
      monitoring system on essential standards of quality and safety in dental
      practices.

PMID- 22878338
TI  - Evaluation of the basic erosive wear examination (BEWE) for use in general dental
      practice.
AB  - OBJECTIVE: The basic erosive wear examination (BEWE) is a relatively new index
      proposed for the screening and recording of tooth wear in adults. The aim of this
      study was to test the validity and reliability of the BEWE. DESIGN: Cross
      sectional study of a sample of 164 adult patients. SETTING: General dental
      practice in East Lancashire, UK in 2010. SUBJECTS: Patients attending for routine
      examination or treatment. MAIN OUTCOME MEASURES: By screening patients with the
      BEWE and comparing the results to the established tooth wear index (TWI) the
      sensitivity and specificity of the BEWE was established.Results The BEWE
      predicted moderate to severe wear (BEWE grade 3) with a sensitivity of 48.6% and
      a specificity of 96.1%, and predicted severe wear with a sensitivity of 90.9% and
      a specificity of 91.5% (also BEWE score 3). Inter- and intra-examiner reliability
      for the BEWE were both moderate (kappa(w) = 0.43 and 0.57 respectively).
      CONCLUSION(S): BEWE scores show a similar distribution to TWI scores and the
      examination is an effective screening test for severe tooth wear. The moderate
      levels of examiner reliability suggests the BEWE scores should be interpreted
      with some caution.

PMID- 22878339
TI  - Rilpivirine, a novel non-nucleoside reverse transcriptase inhibitor for the
      management of HIV-1 infection: a systematic review.
AB  - Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase
      inhibitor (NNRTI). It remains active against HIV strains harbouring mutations
      that affect first-generation agents. RPV is dosed once daily with food and has
      been coformulated into a single tablet containing tenofovir and emtricitabine.
      Two Phase III studies of treatment-naive patients found RPV and efavirenz to have
      similar safety and efficacy. However, suboptimal virological suppression with RPV
      occurred more commonly in patients with higher baseline viral loads (>100,000
      copies/ml). The most common mutation that emerged during RPV therapy was E138K,
      which often occurred in combination with M184I. E138K is likely to cause cross
      resistance to other NNRTIs thereby limiting the further utilization of this
      class.

PMID- 22878340
TI  - Early comfort after supracondylar pinning: commentary on an article by Gaia
      Georgopoulos, MD, et al.: "The efficacy of intra-articular injections for pain
      control following the closed reduction and percutaneous pinning of pediatric
      supracondylar humeral fractures. A randomized controlled trial".

PMID- 22878341
TI  - Dietary intake measured from a self-administered, online 24-hour recall system
      compared with 4-day diet records in an adult US population.
AB  - The objective of this study was to compare nutrient intake of two 24-hour recalls
      collected using the Automated Self-Administered 24-Hour Dietary Recall to a 4-day
      food record. A convenience sample of university-affiliated adults was chosen
      because of the diverse population at this university. Ninety-three participants
      completed the 4-day record and were then prompted to complete two 24-hour recalls
      within 2 weeks after. Pearson correlation coefficients were calculated for
      nutrient intake and Healthy Eating Index 2005 (HEI-2005), a summary measure of
      diet quality. Nutrients and HEI-2005 were also divided into quartiles and percent
      agreement and kappa values were calculated. Results indicated that mean nutrient
      intakes were similar across the recall and record. Pearson correlations comparing
      the record and recall ranged from 0.16 to 0.78; with most correlations being
      between 0.4 and 0.6. For quartiles of dietary intake, percent agreement was
      moderately high (62.6% to 79.8%), with low to moderate kappa values (kappa=0.11
      to 0.52). The 24-hour recall provided a good overall ranking of intake compared
      to a 4-day food record. Overall correlations and percent agreement were moderate
      across the nutrients and HEI-2005, suggesting that the 24-recalls may have been
      capturing different information than the food record in our population.
      Individual researchers will need to weigh the benefits of a more automated
      system, such as efficiency, against the potential loss of food item detail and
      potential need for larger sample sizes, for their particular study populations.

PMID- 22878342
TI  - The physiology of sterol nutrition in the pea aphid Acyrthosiphon pisum.
AB  - The phloem sap of fava bean (Vicia faba) plants utilized by the pea aphid
      Acyrthosiphon pisum contains three sterols, cholesterol, stigmasterol and
      sitosterol, in a 2:2:1 ratio. To investigate the nutritional value of these
      sterols, pea aphids were reared on chemically-defined diets containing each
      sterol at 0.1, 1 and 10MUgml(-1) with a sterol-free diet as control. Larval
      growth rate and aphid lifespan did not vary significantly across the diets,
      indicating that sterol reserves can buffer some performance indices against a
      shortfall in dietary sterol over at least one generation. However, lifetime
      reproductive output was depressed in aphids on diets containing stigmasterol or
      no sterol, relative to diets supplemented with cholesterol or sitosterol. The
      cholesterol density of embryos in teneral adults was significantly higher than in
      the total body; and the number and biomass of embryos in aphids on diets with
      stigmasterol and no sterols were reduced relative to diets with cholesterol or
      sitosterol, indicating that the reproductive output of the pea aphid can be
      limited by the amount and composition of dietary sterol. In a complementary RNA
      seq analysis of pea aphids reared on plants and diets with different sterol
      contents, 7.6% of the 17,417 detected gene transcripts were differentially
      expressed. Transcript abundance of genes with annotated function in sterol
      utilization did not vary significantly among treatments, suggesting that the
      metabolic response to dietary sterol may be mediated primarily at the level of
      enzyme function or metabolite concentration.

PMID- 22878343
TI  - Transforming growth factor beta-1 and incidence of heart failure in older adults:
      the Cardiovascular Health Study.
AB  - CONTEXT: Transforming growth factor-beta1 (TGF-B1) is a highly pleiotropic
      cytokine whose functions include a central role in the induction of fibrosis.
      OBJECTIVE: To investigate the hypothesis that elevated plasma levels of TGF-B1
      are positively associated with incident heart failure (HF). PARTICIPANTS AND
      METHODS: The hypotheses were tested using a two-phase case-control study design,
      ancillary to the Cardiovascular Health Study - a longitudinal, population-based
      cohort study. Cases were defined as having an incident HF event after their 1992
      1993 exam and controls were free of HF at follow-up. TGF-B1 was measured using
      plasma collected in 1992-1993 and data from 89 cases and 128 controls were used
      for analysis. The association between TGF-B1 and risk of HF was evaluated using
      the weighted likelihood method, and odds ratios (OR) for risk of HF were
      calculated for TGF-B1 as a continuous linear variable and across quartiles of TGF
      B1. RESULTS: The OR for HF was 1.88 (95% confidence intervals [CI] 1.26-2.81) for
      each nanogram increase in TGF-B1, and the OR for the highest quartile (compared
      to the lowest) of TGF-B1 was 5.79 (95% CI 1.65-20.34), after adjustment for age,
      sex, C-reactive protein, platelet count and digoxin use. Further adjustment with
      other covariates did not change the results. CONCLUSIONS: Higher levels of plasma
      TGF-B1 were associated with an increased risk of incident heart failure among
      older adults. However, further study is needed in larger samples to confirm these
      findings.

PMID- 22878344
TI  - Interleukin-32: a predominantly intracellular proinflammatory mediator that
      controls cell activation and cell death.
AB  - In this review, we will discuss the current knowledge on IL-32 and provide new
      insights regarding the biological function of IL-32. IL-32 is seen as a cytokine
      that can induce a range of proinflammatory mediators and contribute to autoimmune
      diseases, such as rheumatoid arthritis, however present knowledge demonstrates
      that IL-32 is not a classical cytokine. We present the history of this cytokine,
      the role of IL-32 in several diseases and discuss a possible novel role of
      intracellular IL-32 in cell homeostasis. Taken into account the observed
      biological functions of IL-32, it may belong to a class of cytokines, like IL
      1alpha, IL-33, and IL-37, with both intracellular and extracellular functions.

PMID- 22878346
TI  - Reduction of peripherally inserted central catheter-associated DVT.
AB  - BACKGROUND: As peripherally inserted central catheter (PICC) use has increased,
      so has the upper extremity DVT rate. PICC diameter may pose the most modifiable
      risk for PICC-associated DVT. METHODS: A 3-year, prospective, observational study
      of all PICC insertions by a specially trained and certified team using a
      consistent and replicable approach was conducted at a 456-bed, level I trauma and
      tertiary referral hospital during January 1, 2008, through December 31, 2010. An
      intensified effort by the PICC team in 2010 was introduced to discuss and reach
      interdisciplinary consensus on the need for each lumen of the PICC and a change
      to smaller diameter 5F triple-lumen PICC. RESULTS: Significantly more 4F single
      lumen PICCs were used during 2010 (n = 470) compared with 2008 and 2009 (n = 338,
      382; P < .0001). DVT rates were similar with the use of 5F triple-lumen PICCs in
      2010 as 5F double-lumen PICCs and lower rates than 6F triple-lumen catheters used
      in 2008 and 2009. The PICC-associated DVT rate was significantly lower (1.9% vs
      3.0%, P < .04) in 2010 compared with 2008 and 2009. The cost and length of stay
      attributable to PICC-associated DVT were $15,973 and 4.6 days. CONCLUSIONS: A
      significant increase in the use of single-lumen PICCs in addition to the
      institutional adoption of smaller 5F triple-lumen PICCs was associated with a
      significant decrease in the rate of PICC-associated DVT.

PMID- 22878347
TI  - Letter from the U.K.: the state of the art.

PMID- 22878349
TI  - A telephone survey of intensive care unit handover practices in the UK.

PMID- 22878348
TI  - The effects of three specific conditions related to critical care on adrenal
      function in children.
AB  - PURPOSE: To evaluate the effects of three specific conditions related to critical
      care on adrenal function with special regard to the levels of serum cortisol,
      corticotropin (ACTH), dehydroepiandrosterone sulfate, and cytokines. METHODS: The
      study enrolled a total of 74 children who were divided into three groups. Group 1
      comprised 23 patients who had acute critical illness (ACI) associated with severe
      sepsis/septic shock. Group 2 comprised 27 patients who had ACI without sepsis.
      Group 3 comprised 24 patients who underwent major surgery. Blood samples were
      obtained for baseline measurements and a low-dose ACTH stimulation test (LD-ST)
      was performed. Serial ACTH and cortisol levels were measured with an interval of
      3 days and LD-ST was repeated on day 14 for all groups. RESULTS: Baseline
      cortisol, ACTH, and dehydroepiandrosterone sulfate levels were significantly
      higher in patients with adrenal insufficiency (AI) than those of without AI. AI
      was detected in four patients in group 1, seven in group 2, and ten in group 3.
      Consecutive cortisol and ACTH levels did not differ significantly among the
      groups. On day 14, the recovery rate in patients with AI was 82 % in the whole
      group. Patient's age and interleukin-10 level were found to be independent
      predictors of AI. CONCLUSIONS: A considerable proportion of patients in these
      three groups had AI with a high spontaneous recovery rate in 2 weeks. The
      presence of sepsis was not associated with an increased risk of AI. Our serial
      cortisol and ACTH values in these different groups could be used as reference
      values for further studies.

PMID- 22878350
TI  - Focal neurological deficit with tricuspid endocarditis and patent foramen ovale.

PMID- 22878351
TI  - Comparison of the CAM2 and NAL-NL2 hearing aid fitting methods.
AB  - OBJECTIVE: To compare preference judgments for sounds processed via a simulated
      five-channel compression hearing aid with gains and compression ratios selected
      according to two recently introduced fitting methods, CAMEQ2-HF (hereafter named
      CAM2) and NAL-NL2. DESIGN: There were 15 participants with sloping sensorineural
      hearing loss. They had mild losses, typical of people who might be candidates for
      wide-bandwidth hearing aids. Within a given trial, the same segment of sound was
      presented twice in succession to one ear, once with CAM2 settings and once with
      NAL-NL2 settings, in random order. The participant had to indicate which one was
      preferred and by how much. Judgments of overall sound quality were obtained for
      female and male speech in quiet and for four types of music (classical, jazz, a
      man singing, and percussion). Judgments of speech clarity were obtained for
      female and male speech in speech-shaped noise, female speech in a male-talker
      background, and male speech in a female-talker background. Factors investigated
      included compression speed (slow or fast) and input sound level (50, 65, or 80 dB
      SPL). RESULTS: The pattern of the results was reasonably consistent across
      participants, but the magnitude of the effects was small. For judgments of
      overall sound quality, nine participants preferred CAM2 relative to NAL-NL2, and
      the remainder showed no clear preference. There was a significant overall
      preference for CAM2. The preference for CAM2 over NAL-NL2 in overall sound
      quality was present for all types of stimuli, both compression speeds, and all
      three levels. For judgments of the clarity of speech in noise, five participants
      preferred CAM2 over NAL-NL2, one showed the opposite preference, and the
      remainder showed no clear preference. There was a significant overall preference
      for CAM2. The preference for CAM2 over NAL-NL2 in the context of clarity of
      speech in noise was present for all types of stimuli, both compression speeds,
      and all three levels. For judgments of the clarity of speech in a background
      talker, CAM2 was significantly preferred overall relative to NAL-NL2, but the
      effect was very small. CONCLUSIONS: For participants with mild sloping hearing
      loss, a simulated hearing aid unilaterally fitted using CAM2 was preferred over
      the same aid fitted using NAL-NL2 for overall sound quality and the clarity of
      speech in noise. Preferences differed only very slightly for the clarity of
      speech in a background talker. Further work is needed to establish whether
      similar preferences would be found in everyday life.

PMID- 22878352
TI  - Abnormal left ventricular vortex flow patterns in association with left
      ventricular apical thrombus formation in patients with anterior myocardial
      infarction: a quantitative analysis by contrast echocardiography.
AB  - BACKGROUND: The current study was designed to investigate the correlation between
      the left ventricular (LV) vortex flow pattern and LV apical thrombus formation in
      patients with acute anterior wall myocardial infarction (MI). METHODS AND
      RESULTS: Fifty-seven patients with acute anterior wall MI were enrolled in this
      study. Eighteen patients with apical thrombus (thrombus group) and 39 patients
      without apical thrombus (non-thrombus group) underwent 2-dimensional contrast
      echocardiography (CE). Morphology and pulsatility parameters of the LV vortex
      were measured using Omega flow((r)) and compared between the 2 groups. In the
      thrombus group, the vortex was located more centrally and did not extend to the
      apex. In the thrombus group, quantitative vortex parameters of vortex depth
      (0.409+/-0.101 vs. 0.505+/-0.092, respectively; P=0.002) and relative strength
      (1.574+/-0.310 vs. 1.808+/-0.376, respectively, P=0.034) were significantly lower
      than the non-thrombus group. Following multivariate analysis, the vortex depth
      below 0.45 remained a significant independent parameter for formation of the LV
      apical thrombus (odds ratio 9.714, 95% confidence interval 1.674-56.381,
      P=0.011). CONCLUSIONS: These findings suggest that the location and pulsatility
      power of the LV vortex are strongly associated with the LV thrombus formation in
      patients with anterior MI. Therefore, LV vortex flow analysis using CE can be
      clinically useful for characterizing and quantifying the risk of LV apical
      thrombus in patients with anterior MI.

PMID- 22878353
TI  - Plasma N-terminal pro-brain natriuretic peptide levels identifying left
      ventricular diastolic dysfunction in patients with preserved ejection fraction.
AB  - BACKGROUND: Diagnosis of left ventricular (LV) diastolic dysfunction by blood
      testing is expedient in the clinical setting. METHODS AND RESULTS: In 98 patients
      with LV ejection fraction >=50% who underwent cardiac catheterization for
      evaluation of coronary artery disease, LV pressure (LVP) was measured using a
      catheter-tipped micromanometer. A time constant, tau, of LV relaxation was
      computed from LVP decay; the inertia force (IF) of late systolic aortic flow, a
      surrogate index of LV elastic recoil, was also computed from the LVP-dP/dt
      relation (phase loop). Patients were classified into 2 groups: those with
      impaired LV relaxation (tau >=48 ms) and those with preserved LV relaxation (tau
      <48 ms). Patients were also classified into another 2 groups: those with IF
      (>=0.5 mmHg) and those without (<0.5 mmHg). Plasma N-terminal pro-brain
      natriuretic peptide (NT-proBNP) >=56.5 pg/ml had a sensitivity of 100%,
      specificity of 52.5%, and negative predictive value of 100% for identifying
      impaired LV relaxation. NT-proBNP >=244.5 pg/ml had a sensitivity of 62.5% and
      specificity of 93.9% for detecting lack of IF. CONCLUSIONS: NT-proBNP level <56.5
      pg/ml could be used as a value to sensitively identify patients with preserved LV
      systolic and diastolic function among those with coronary artery disease. NT
      proBNP level >=244.5 pg/ml is able to specifically detect a lack of IF and has
      potential for specifically diagnosing LV isolated diastolic dysfunction.

PMID- 22878354
TI  - Risk factors for work-related injuries among university student employees.
AB  - This study identified contributing risk factors in the occurrence of work-related
      injuries among university students employed at a single university. Four hundred
      seventy-six student employees completed the survey in March 2010. The majority of
      respondents were female (66%) and the average age of all respondents was 20.7 yr.
      A pre-validated survey instrument was taken from the Youth Employment and School
      Study (YESS) and contained scales for the risk factors of interest. Results show
      significant differences in the amount of work-school conflict, boredom, workplace
      hazards, and workload between injured and non-injured groups. Odds ratios show
      that physical hazards and heavy workload have a significant two-fold increase on
      the likelihood of 1-3 injuries (OR=1.80, 1.09-3.00; OR=1.72, 1.12-2.60), and a 2
      to 3 fold increase in 4 or more injuries (OR=2.94, 1.65-5.24; OR=2.34,1.51-3.64).
      Good supervisor relations appear to reduce injury risk (OR=0.48, 0.25-0.91;
      OR=0.59, 0.32-1.09). Reducing workload stress, teaching students how to manage
      the workload, reducing exposure to physical hazards, and providing examples of
      standard work practices may reduce the number of injuries seen in the population.

PMID- 22878355
TI  - Outpatient visits by dentists: a nationwide cohort study in Taiwan.
AB  - We conducted a cohort study of 7,760 dentists in Taiwan between 2003 and 2007 to
      assess the risk of outpatient visit among dentists. Control groups included
      physicians and other health personnel. Over the 5-yr study period, the dentist
      cohort made a total of 270,712 outpatient visits, representing an incidence rate
      of 7,038 visits /10(3) person-years. Compared to physicians, dentists experienced
      a significantly reduced covariate adjusted rate ratio (ARR) for all-cause visits
      (ARR=0.59, 95%CI=0.58-0.59), as well as for nearly all other causes, except
      neoplasm (ARR=1.06, 95%CI=1.02-1.09). Compared to other health personnel, the
      dentists still experienced a significantly reduced ARR for all causes (ARR=0.70),
      but had a slightly but significantly increased risk for
      endocrine/metabolic/immunity (ARR=1.04, 95%CI=1.02-1.05) and mental (ARR=1.04,
      95%CI=1.01-1.07) disorders. Although the dentists in Taiwan utilized lesser
      outpatient visits than did their medical colleagues, they tended to have slightly
      higher rates of outpatient visits for neoplasm, endocrine/metabolic/immunity
      disorders, and mental illnesses. Policy makers and hospital administrators must
      not overlook dentists' potentially unseen health problems. A mandatory periodical
      physical examination for dentists can seriously be considered.

PMID- 22878357
TI  - Long working hours in Korea: results of the 2010 Working Conditions Survey.
AB  - Long working hours adversely affect workers' safety and health. In 2004, Korea
      passed legislation limiting the working week to 40 h, to improve quality-of-life
      and to increase business competitiveness. In the present study, we explored the
      characteristics of work in Korea and compared our data of the second Korean
      Working Conditions Survey (KWCS) with those of the first KWCS. We found that the
      average number of hours worked weekly has been reduced but the proportions of
      workers who work for more than 48 h per week has increased over the 4 yr between
      the two Korean surveys in all categories studied (male, female, employee, self
      employed, and employer). We also found that self-employed and employers work much
      longer hours than do employees, who are protected by the Labor Standards Act.
      This was particularly true in the accommodation and food service sectors. In
      conclusion, Korean workers work longer than do workers of EU countries. The use
      of average figures masks differences in the numbers of working hours among those
      engaged in various types of employment, or in certain work sectors. Therefore,
      the Korean government should not simply monitor reductions in average weekly
      working hours, but should identify employees working for over 60 h weekly, and
      reduce their working time.

PMID- 22878356
TI  - Aluminium-maltolate-induced impairment of learning, memory and hippocampal long
      term potentiation in rats.
AB  - Recently, aluminium (Al) has been proposed to be one of the environmental factors
      responsible for cause Alzheimer's disease (AD). However, the relationship between
      Al and AD is controversial. To investigate the effects of subchronic Aluminium
      maltolate (Al (mal)(3)) exposure on the behavioral, electrophysiological
      functions. Forty Sprague-Dawley (SD) rats were randomly distributed into five
      groups. Over two months, rats in the saline group received daily intraperitoneal
      (i.p.) injections 0.9% saline, rats in the maltolate group received 7.56 mg/kg
      maltolate, and rats in the 0.27, 0.54, 1.08 mg/kg Al (mal)(3) groups received
      i.p. administrations of these three doses, respectively. Neural behavior was
      assessed in Morris water maze. Long-term potentiation (LTP) in hippocampus was
      recorded. Al content in the neocortex was determined using a graphite furnace
      atomic absorption spectrophotometer. Our studies indicate that subchronic Al
      (mal)(3) exposure significantly impaired spatial learning and memory abilities,
      suppressed the LTP in the CA1 hippocampal area, and elevated Al levels in
      cerebral cortex in a dose-dependent fashion. In conclusion, low doses of Al
      (mal)(3) can still lead to dramatic Al accumulation in the brain, severely impair
      learning and memory capacities, and hippocampal LTP.

PMID- 22878358
TI  - Application of local exhaust ventilation system and integrated collectors for
      control of air pollutants in mining company.
AB  - Local exhaust ventilation (LEV) systems and integrated collectors were designed
      and implemented in a mining company in order to control emitted air pollutant
      from furnaces. The LEV was designed for capture and transition of air pollutants
      emitted from furnaces to the integrated collectors. The integrated collectors
      including four high efficiency Stairmand model cyclones for control of
      particulate matter, a venturi scrubber for control of the fine particles, SO(2)
      and a part of H(2)S to follow them, and a packed scrubber for treatment of the
      residual H(2)S and SO(2) were designed. Pollutants concentration were measured to
      determine system effectiveness. The results showed that the effectiveness of LEV
      for reducing workplace pollution is 91.83%, 96.32% and 83.67% for dust, SO(2) and
      H(2)S, respectively. Average removal efficiency of particles by combination of
      cyclone and venturi scrubber was 98.72%. Average removal efficiency of SO(2) and
      H(2)S were 95.85% and 47.13% for the venturi scrubber and 68.45% and 92.7% for
      the packed bed scrubber. The average removal efficiency of SO(2) and H(2)S were
      increased to 99.1% and 95.95% by the combination of venturi and packed bed
      scrubbers. According to the results, integrated collectors are a good air
      pollution control option for industries with economic constraints and ancient
      technologies.

PMID- 22878359
TI  - Vascularised local and free flaps in anterior skull base reconstruction.
AB  - Lesions of the anterior skull base often require sufficient closure in order to
      prevent cerebrospinal fluid (CSF) leak, ascending infection and/or brain tissue
      prolapse. The transfer of devitalized autologous, allogenic or xenogeneic
      material is not always sufficient particularly not in larger defects or in the
      recurrent situation. Here the transfer of vascularised tissue seems to be more
      appropriate. The anterior skull base with various complex defects of 41 patients
      was reconstructed in an interdisciplinary setting by vascularised, autologous
      tissue transfer. Minor defects (<2.5 cm in max. diameter), generally occurring
      after extended endoscopic skull base approaches (n = 26, among those meningiomas,
      recurrent CSF fistulas, chordoma, chondroblastoma, metastasis, nasal fistula),
      were reconstructed by a local, vascularized pedicled mucosal flap of the lower
      turbinate (n = 3) or septum (n = 23). Patients with major defects (>2.5 cm in
      max. diameter, n = 15), comprising those with malignoma, meningoencephalocele,
      aneurysmatic bone cyst and trauma, were repaired by a "sandwich technique" with a
      combination of calvarian split and galea periosteum flap in 10 patients, in one
      case with a temporalis muscle flap, while in 4 further patients free vascularised
      radial forearm flaps were used for revision after multiple unsuccessful
      operations elsewhere. After a mean follow-up time of 30.5 months 38 of the 41
      cases were successfully repaired with respect to prevention and treatment of CSF
      leakage or brain tissue prolapse, only 3 cases needed surgical revision. The
      reconstruction of the anterior skull base bearing complex lesions is feasible
      using vascularised, autologous local and also distal tissue transfer in a close
      interdisciplinary cooperation.

PMID- 22878361
TI  - Cholestasis, bronchopulmonary dysplasia, and lipid profile in preterm infants
      receiving MCT/omega-3-PUFA-containing or soybean-based lipid emulsions.
AB  - BACKGROUND: This study aimed to compare the effect of 2 lipid emulsions (LEs), a
      medium-chain triglyceride (MCT)/omega-3-polyunsaturated fatty acid (PUFA)
      containing LE and a soybean-based LE, on the incidence of neonatal cholestasis,
      bronchopulmonary dysplasia (BPD), and lipid profile of preterm infants. Patients
      and METHODS: In this prospective, observational study, 2 groups of preterm
      neonates, the very low birth weight (VLBW) (n = 129) and the low birth weight
      (LBW) groups (n = 153), which received parenteral LEs for at least 7 days, were
      included. Infants received either MCT/omega-3-PUFA-containing LE (SMOFlipid,
      subgroup I) or soybean-based LE (Intralipid, subgroup II) according to the
      attending neonatologist's preference and availability. Full biochemical
      assessment was performed on days of life 15, 30, and 45 and on discharge.
      RESULTS: Of the VLBW infants, 7.4% and 13.3% of infants in subgroups I and II,
      respectively, developed cholestasis (P = .39; odds ratio [OR], 0.52; 95%
      confidence interval [CI], 0.15-1.76). The duration of LE administration was
      independently associated with cholestasis (P < .001; OR, 0.925; 95% CI, 0.888
      0.963). The maximum amounts of lipids administered ranged between 1.6 and 3.6
      g/kg/d in both VLBW subgroups. The VLBW subgroup I had lower incidence of BPD,
      lower alkaline phosphatase and phosphate, higher high-density lipoprotein (HDL),
      and lower cholesterol-to-HDL ratio on discharge than the VLBW subgroup II. The
      type of LE was independently associated with BPD and alkaline phosphatase. In the
      LBW group, the type of LE was not associated with clinical and biochemical
      parameters. CONCLUSION: In VLBW infants, the MCT/omega-3-PUFA-containing LE
      administration is associated with decreased BPD and more favorable lipoprotein
      profile. Although a trend toward a lower incidence of cholestasis was observed, a
      preventive effect of MCT/omega-3-PUFA-containing LE on parenteral nutrition
      associated cholestasis is not supported.

PMID- 22878362
TI  - Phytochemicals and cancer risk: a review of the epidemiological evidence.
AB  - A number of epidemiological studies have investigated associations between
      various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the
      two most commonly studied classes of phytochemicals; phytosterols,
      isothiocyanates, and chlorophyll also have been investigated, although to a much
      lesser extent. Because there have been no systematic reviews of the literature on
      all phytochemicals and cancer risk to date, this article systematically reviews
      96 published epidemiological studies that examined associations between
      phytochemicals and cancer risk. Most studies found null associations between
      individual phytochemicals and cancer risk at various sites. In addition, results
      from past studies have been largely inconsistent, and observed associations have
      been of relatively modest magnitude. The most consistent protective effects were
      observed for higher levels--dietary intake, serum, plasma, or urinary metabolites
      -of beta-carotene and renal cell cancer, beta-cryptoxanthin and lung cancer,
      isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer,
      lignans and postmenopausal breast cancer, and flavonoids and lung cancer.
      Although elevated risk of certain cancers with higher levels of certain
      phytochemicals was observed, an insufficient pool of studies examining the same
      associations or inconsistent findings across studies limit the ability to
      conclude that any one phytochemical increases cancer risk. Additional research is
      needed to support previously identified associations in cases where only one
      study has examined a particular relationship. Importantly, continued research
      efforts are needed to evaluate the cumulative and interactive effects of numerous
      phytochemicals and phytochemical-rich foods on cancer risk.

PMID- 22878363
TI  - Fluoride-bridged {Ln2Cr2} polynuclear complexes from semi-labile mer-[CrF3(py)3]
      and [Ln(hfac)3(H2O)2].
AB  - The trifluorido complex mer-[CrF(3)(py)(3)] (py = pyridine) reacts with 1 equiv.
      of [Ln(hfac)(3)(H(2)O)(2)] and depending on the solvent forms the tetranuclear
      clusters [Cr(2)Ln(2)(MU-F)(4)(MU-OH)(2)(py)(4)(hfac)(6)], 1Ln, and [Cr(2)Ln(2)(MU
      F)(4)F(2)(py)(6)(hfac)(6)], 2Ln, in acetonitrile and 1,2-dichloroethane,
      respectively (Ln = Y, Gd, Tb, Dy, Ho, and Er; hfacH = 1,1,1,5,5,5
      hexafluoroacetylacetone). Reaction with [Dy(hfac)(3)(H(2)O)(2)] in
      dichloromethane produces the dinuclear cluster [CrDy(MU
      F)F(OH(2))(py)(3)(hfac)(4)], 3Dy. All the clusters feature fluoride bridges
      between the chromium(III) and lanthanide(III) centres. Fits of susceptibility
      data for 1Gd and 2Gd reveal the fluoride-mediated chromium(III)-lanthanide(III)
      exchange interactions to be 0.43(5) cm(-1) and 0.57(7) cm(-1), respectively (in
      the H = JS1. S2 convention). Heat capacity measurements on 2Gd reveal a moderate
      magneto-caloric effect (MCE) reaching -DeltaS(m)(T) = 11.4 J kg(-1) K(-1) for
      DeltaB(0) = 9 T -> 0 T at T = 4.1 K. Out-of-phase alternating-current
      susceptibility (chi'') signals are observed for 1Dy, 2Dy and 2Tb, demonstrating
      slow relaxation of the magnetization.

PMID- 22878364
TI  - Joint replacement costs in the era of healthcare reform: commentary on an article
      by James C. Robinson, PhD, MPH, et al.: "Variability in costs associated with
      total hip and knee replacement implants".

PMID- 22878365
TI  - Mucinous nevus with fat:  an unusual case report and literature review.
AB  - Mucinous nevus is a rare entity classified as either cutaneous mucinosis or
      connective tissue nevi. Clinically, multiple papules or plaques develop at birth
      or in early adulthood and grow to form verrucous or nevoid feature with a
      unilateral or often zosteriform distribution on the trunk. Histopathologically,
      it is characterized by mucin deposits localized in the papillary dermis, clearly
      distinguishing this entity from other types of cutaneous mucinosis. A 18-year-old
      male presented with multiple, skin-colored, pinhead to pea-sized, grouped, flat
      tapped, soft papules on the back. This skin lesion was found accidentally 3 years
      ago with no symptom. Histologic findings revealed an acanthotic epidermis with
      thin elongated rete ridges and orthohyperkeratosis. In papillary dermis, fine
      collagen fibers were interspersed in an abundant ground substance that stained
      positively with Alcian blue at pH2.5. Herein the authors describe an unusual case
      of mucinous nevus and review the relevant literature.

PMID- 22878366
TI  - Mitotic rate in cutaneous melanomas <=1 mm in thickness: a prospective study.
AB  - The mitotic rate (MR) of malignant melanoma (MM) refers to the number of mitoses
      per square millimeter. Studies have suggested that it is an independent
      prognostic variable predicting survival in patients with MM, and it was recently
      included in the American Joint Committee on Cancer (AJCC) recommendations for
      diagnosis and treatment of MM. The AJCC melanoma staging committee recommends
      using the "hot-spot" approach to determine the MR, whereby it is reported as the
      maximum dermal mitotic figures identified in a 1-mm area of the melanoma. The
      AJCC has recommended that the MR be determined in all melanomas, irrespective of
      Breslow depth or other features. We aimed to quantify the MR in MM <=1 mm in
      thickness and to identify statistical associations between the MR, Breslow depth,
      and Clark level. In addition, we hoped to identify practical issues in
      determining the MR via the hot-spot technique. We conducted a prospective study
      to determine the MR, Breslow depth, and Clark level in MM <=1 mm in thickness.
      Seven melanomas were identified with epidermal mitoses only (7.4%). Sixteen
      melanomas had dermal mitoses (16.8%); of these, the majority (75.0%) contained
      only one mitotic figure. Seventy-nine melanomas had no dermal mitoses (83.2%).
      Seven lesions (7.4%) demonstrated multiple mitoses; 4 with >=2 dermal mitoses/mm
      and 3 with multiple epidermal mitoses. We conclude that thin MM with >1
      mitosis/mm is rare and discuss practical and theoretical issues with determining
      the MR using the hot-spot approach.

PMID- 22878367
TI  - Changes in tumor morphology and cyclin-dependent kinase inhibitor expression in
      metastatic melanoma treated with selective second-generation BRAF inhibitor.
AB  - Dermatologic toxicities associated with anticancer-targeted therapy include hand
      foot skin reactions, vasculitis, cutaneous epithelial proliferations, such as
      keratosis, keratoacanthoma, and invasive squamous cell carcinoma. In this case
      report, we describe alterations of tumor morphology and patterns of cyclin
      dependent kinase inhibitor (CDKI) expression in a patient who received
      GSK2118436, a second-generation RAF inhibitor, for stage IV (M1c) metastatic
      melanoma. To explore the effects of GSK2118436 on the expression patterns of CDKI
      (p16, p21, p27, p57), we immunohistochemically evaluated in vivo melanoma cells
      pre- and posttreated with GSK2118436. After GSK2118436 treatment, the melanoma
      cells decreased in size and demonstrated hyperchromatic nuclei and indistinct
      nucleoli. p16 was strongly expressed in the cytoplasm of pretreated melanoma
      cells and in the nucleus and cytoplasm in posttreated melanoma cells. Expression
      of both p27 (nucleus) and p57 (cytoplasm) was increased in posttreated melanoma
      cells and no significant difference in p21 expression was noted in either pre- or
      posttreated tumor cells. These findings may help explain the molecular mechanisms
      by which tumor cells retain the ability to proliferate. The persistent activation
      of pro-oncogenic activities of CDKI (eg, p27 and p57) and/or compartmentalization
      of p16 in cytoplasm or nucleus may allow tumor cells to bypass BRAF-induced
      senescence mechanisms. Furthermore, awareness of changes in tumor morphology
      after treatment with RAF inhibitors may be helpful in histologic evaluation of
      the spectrum of dermatologic toxicity, which may occur on targeted therapy.

PMID- 22878369
TI  - Circumscribed palmar hypokeratosis associated to a burn scar.
AB  - Circumscribed palmar or plantar hypokeratosis is a volar depression characterized
      by a circular area of well-circumscribed and erythematous skin on the palm or
      sole. It is a benign condition that occurs mainly as an asymptomatic lesion on
      the thenar or hypothenar areas of the palm of middle-aged or elderly patients.
      Since its first description 1 decade ago, the pathogenesis of this entity still
      remains unclear. Herein we report the first case of a circumscribed palmar
      hypokeratosis lesion associated to a burn scar, which corroborates the hypothesis
      of an acquired disorder caused by trauma.

PMID- 22878370
TI  - Are lower rates of surgery amongst older women with breast cancer in the UK
      explained by co-morbidity?
AB  - BACKGROUND: Around 60% of women >= 80 years old, in the UK do not have surgery
      for their breast cancer (vs<10% of younger age groups). The extent to which this
      difference can be accounted for by co-morbidity has not been established.
      METHODS: A Cancer Registry/Hospital Episode Statistics-linked data set identified
      women aged >= 65 years diagnosed with invasive breast cancer (between 1 April
      1997 and 31 March 2005) in two regions of the UK (n=23038). Receipt of surgery by
      age was investigated using logistic regression, adjusting for co-morbidity and
      other patient, tumour and treatment factors. RESULTS: Overall, 72% of older women
      received surgery, varying from 86% of 65-69-year olds to 34% of women aged >= 85
      years. The proportion receiving surgery fell with increasing co-morbidity
      (Charlson score 0=73%, score 1=66%, score 2+=49%). However, after adjustment for
      co-morbidity, older age still predicts lack of surgery. Compared with 65-69-year
      olds, the odds of surgery decreased from 0.74 (95% CI: 0.66-0.83) for 70-74-year
      olds to 0.13 (95% CI: 0.11-0.14) for women aged >= 85 years. CONCLUSION: Although
      co-morbidity is associated with a reduced likelihood of surgery, it does not
      explain the shortfall in surgery amongst older women in the UK. Routine data on
      co-morbidity enables fairer comparison of treatment across population groups but
      needs to be more complete.

PMID- 22878371
TI  - The relationship between components of tumour inflammatory cell infiltrate and
      clinicopathological factors and survival in patients with primary operable
      invasive ductal breast cancer.
AB  - BACKGROUND: The importance of the components of host local inflammatory response
      in determining outcome in primary operable ductal invasive breast cancer is not
      clear. The aim of this study was to examine the relationship between components
      of the tumour inflammatory cell infiltrate and standard clinicopathological
      factors including hormone status (oestrogen receptor (ER), progesterone receptor
      (PR) and human epidermal growth factor receptor (HER)-2), Ki-67 and survival in
      patients with primary operable invasive ductal breast cancer. METHODS: Tumour
      inflammatory cell infiltrate, hormone status (ER, PR and HER-2), Ki-67 and
      standard clinicopathological factors were determined using routine pathological
      and immuno-histochemical techniques in 468 patients. RESULTS: The large majority
      (94%) of ductal tumours had evidence of inflammatory cell infiltrate. The general
      inflammatory cell infiltrate was positively associated with high grade (P<0.001),
      the absence of ER (P<0.001), the absence of PR (P<0.01), the presence of vascular
      invasion (P<0.05) and high lymphocytic infiltrate, plasma cell infiltrate, other
      inflammatory cell infiltrate and macrophage infiltrate (all P<0.001). The median
      follow-up of the survivors was 165 months. During this period, 93 patients died
      of their cancer. On univariate analysis, stratified for ER status, tumour size
      (P<0.01), lymph node involvement (P<0.001), tumour plasma cell infiltrate
      (P<0.001), other inflammatory cell infiltrate (P<0.05) and treatment (P<0.05)
      were associated with poorer cancer-specific survival whereas lymphocyte
      infiltrate (P<0.001) was associated with improved cancer-specific survival. On
      multivariate analysis, stratified for ER status, lymph node involvement (P<0.05)
      was independently associated with poorer cancer-specific survival whereas
      increased tumour lymphocyte infiltrate (P<0.001) was independently associated
      with improved cancer-specific survival. CONCLUSION: The results of this study
      show that, using routine histology, the general inflammatory cell infiltrate was
      a common feature and was positively associated with high grade, the absence of
      ER, the absence of PR, the presence of vascular invasion and high-grade
      infiltration of lymphocytes, plasma cells, other inflammatory cells and
      macrophages. Also, that within a mature cohort of patients, a high lymphocytic
      infiltrate was associated with improved survival, independent of
      clinicopathological characteristics including ER status, in primary operable
      ductal invasive breast cancer. These results rationalise previous work and
      provide a sound basis for future studies in this important area of breast cancer
      research.

PMID- 22878372
TI  - Safety, cost-effectiveness and feasibility of daycase paracentesis in the
      management of malignant ascites with a focus on ovarian cancer.
AB  - BACKGROUND: Paracentesis for malignant ascites is usually performed as an in
      patient procedure, with a median length of stay (LoS) of 3-5 days, with
      intermittent clamping of the drain due to a perceived risk of hypotension. In
      this study, we assessed the safety of free drainage and the feasibility and cost
      effectiveness of daycase paracentesis. METHOD: Ovarian cancer admissions at
      Hammersmith Hospital between July and October 2009 were audited (Stage 1). A
      total of 21 patients (Stage 2) subsequently underwent paracentesis with free
      drainage of ascites without intermittent clamping (October 2010-January 2011).
      Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May
      December 2011). RESULTS: Of 67 patients (Stage 1), 22% of admissions and 18% of
      bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of
      patients (Stage 2) drained completely without hypotension. Of four patients with
      hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved
      complete ascites drainage without complications, or the need for in-patient
      admission in 94.7% of cases (Stage 3), and cost L954 compared with L1473 for in
      patient drainage. CONCLUSIONS: Free drainage of malignant ascites is safe.
      Daycase paracentesis is feasible, cost-effective and reduces hospital admissions,
      and potentially represents the standard of care for patients with malignant
      ascites.

PMID- 22878373
TI  - Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in
      the UK Million Women Study.
AB  - BACKGROUND: Previous research suggests associations of lower alcohol intake and
      higher tobacco consumption with increased risks of haematological malignancy. The
      prospective Million Women Study provides sufficient power for reliable estimates
      of subtype-specific associations in women. METHODS: Approximately 1.3 million
      middle-aged women were recruited in the United Kingdom during 1996-2001 and
      followed for death, emigration and cancer registration until 2009 (mean 10.3
      years per woman); potential risk factors were assessed by questionnaire. Adjusted
      relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162
      incident cases of haematological malignancy were recorded, including 7047
      lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers,
      higher intake was associated with lower risk of lymphoid malignancies, in
      particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per
      day (95% confidence interval 0.75-0.96)), follicular lymphoma (0.86 (0.76-0.98))
      and plasma cell neoplasms (0.86 (0.77-0.96)). Among never- and current smokers,
      higher cigarette consumption was associated with increased risk of Hodgkin
      lymphoma (1.45 per 10 cigarettes per day (1.22-1.72)), mature T-cell malignancies
      (1.38 (1.10-1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31
      1.55)). CONCLUSION: These findings confirm and extend existing evidence for
      associations of subtypes of haematological malignancy with two common exposures
      in women.

PMID- 22878374
TI  - Comparison of the prognostic value of inflammation-based prognostic scores in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: Inflammation-based prognostic scores including the Glasgow Prognostic
      Score (GPS), neutrophil to lymphocyte ratio (NLR), and Prognostic Nutritional
      Index (PNI) are associated with survival in patients with hepatocellular
      carcinoma (HCC). The aim of this study was to investigate the prognostic value of
      these inflammation-based prognostic scores in patients with HCC. METHODS: In
      total, 150 patients with newly diagnosed HCC were prospectively evaluated.
      Patients were divided according to the GPS, modified GPS, NLR, platelet to
      lymphocyte ratio (PLR), Prognostic Index (PI), and PNI. The area under the
      receiver operating characteristics curve (AUC) was calculated to compare the
      predictive ability of each of the scoring systems. A univariate and multivariate
      analysis were performed to identify the clinicopathological variables associated
      with overall survival. RESULTS: The GPS consistently had a higher AUC value at 6
      months (0.768), 12 months (0.787), and 24 months (0.758) in comparison with other
      inflammation-based prognostic scores. A multivariate analysis showed that the GPS
      was independently associated with overall survival. CONCLUSION: This study
      demonstrates that the GPS, an inflammation-based prognostic score, is an
      independent marker of poor prognosis in patients with HCC and is superior to the
      other inflammation-based prognostic scores in terms of prognostic ability.

PMID- 22878375
TI  - The TERT variant rs2736100 is associated with colorectal cancer risk.
AB  - BACKGROUND: Polymorphic variation at the 5p15.33 (TERT-CLPTM1L) locus is
      associated with the risk of many cancers but a relationship with colorectal
      cancer (CRC) risk has yet to be defined. METHODS: We used data from six genome
      wide association studies (GWAS) of CRC, linkage disequilibrium mapping and
      imputation, to examine the relationship between 73 single-nucleotide
      polymorphisms at 5p15.33 and CRC risk in detail. RESULTS: rs2736100, which
      localises to intron 2 of TERT, provided the strongest evidence of an association
      with CRC (P=2.28 * 10-4). The association was also shown in an independent series
      of 10 047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven
      studies (totalling 16 039 cases, 16 430 controls) provided increased evidence of
      association (P=2.49 * 10-5; per allele odds ratio=1.07). The association of
      rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants
      previously identified. CONCLUSION: The rs2736100 association demonstrates an
      influence of variation at 5p15.33 on CRC risk and further evidence that the
      5p15.33 (TERT-CLPTM1L) locus has pleiotropic effects (reflecting generic or
      lineage-specific effects) on cancer risk.

PMID- 22878376
TI  - Stopping clinical trials early for futility: retrospective analysis of several
      randomised clinical studies.
AB  - BACKGROUND: Many clinical trials show no overall benefit. We examined futility
      analyses applied to trials with different effect sizes. METHODS: Ten randomised
      cancer trials were retrospectively analysed; target sample size reached in all.
      The hazard ratio indicated no overall benefit (n=5), or moderate (n=4) or large
      (n=1) treatment effects. Futility analyses were applied after 25, 50 and 75% of
      events were observed, or patients were recruited. Outcomes were conditional power
      (CP), and time and cost savings. RESULTS: Futility analyses could stop some
      trials with no benefit, but not all. After observing 50% of the target number of
      events, 3 out of 5 trials with no benefit could be stopped early (low CP <= 15%).
      Trial duration for two studies could be reduced by 4-24 months, saving L44 000
      231 000, but the third had already stopped recruiting, hence no savings were
      made. However, of concern was that 2 of the 4 trials with moderate treatment
      effects could be stopped early at some point, although they eventually showed
      worthwhile benefits. CONCLUSIONS: Careful application of futility can lead to
      future patients in a trial not being given an ineffective treatment, and should
      therefore be used more often. A secondary consideration is that it could shorten
      trial duration and reduce costs. However, studies with modest treatment effects
      could be inappropriately stopped early. Unless there is very good evidence for
      futility, it is often best to continue to the planned end.

PMID- 22878377
TI  - An analysis of fusion cage migration in unilateral and bilateral fixation with
      transforaminal lumbar interbody fusion.
AB  - PURPOSE: To investigate if instrumentation (unilateral vs. bilateral fixation)
      has an effect on the rate of fusion cage migration. METHODS: This clinical study
      of transforaminal lumbar interbody fusion involved a prospective group of 116
      patients who were randomly assigned to either unilateral (n = 57) or bilateral (n
      = 59) fixation. Fourteen were lost to follow-up (11 from the unilateral group and
      3 from the bilateral group). RESULTS: The unilateral fixation group consisted of
      20 male and 26 female patients. In the unilateral group, the mean age was 53.5
      years (range, 18-77), and the preoperative diagnosis consisted of degenerative
      disc disease, with or without herniated disc (n = 44), and degenerative
      spondylolisthesis with spinal stenosis (n = 2). The bilateral fixation group
      consisted of 20 male and 36 female patients. In the bilateral group, the mean age
      was 55.7 years (range, 26-82), and the preoperative diagnosis consisted of
      degenerative disc disease, with or without herniated disc (n = 40), and
      degenerative spondylolisthesis with spinal stenosis (n = 16). A total of 17 cases
      of cage migration were found; of these, 11 were from the unilateral group and 6
      from the bilateral group, resulting in rates of cage migration of 23 and 11 % (p
      = 0.03), respectively. In regard to migration cases, 5 were male and 12 were
      female. Ages ranged from 27 to 79 years (mean age, 55 years). CONCLUSION: We
      conclude that unilateral fixation is not stable enough to prevent fusion cage
      migration in some patients who undergo TLIF.

PMID- 22878378
TI  - Characteristics of idiopathic atlanto-axial subluxation: a comparative
      radiographic study in patients with an idiopathic etiology and those with
      rheumatoid arthritis.
AB  - OBJECTIVE: Atlanto-axial subluxation (AAS) is caused by multiple conditions;
      however, idiopathic AAS patients without RA, upper-cervical spine anomalies or
      any other disorder are rarely encountered. This study retrospectively
      investigated the radiographic findings in idiopathic AAS patients, and clarified
      the differences between those AAS patients and those due to RA. METHODS: Fifty
      three patients with AAS treated by transarticular screw fixation were reviewed.
      The subjects included 8 idiopathic patients (ID group) and 45 RA patients (RA
      group). The study investigated the atlanto-dental interval (ADI) value and space
      available for spinal cord (SAC) at the neutral and maximal flexion position.
      RESULTS: The average ADI value at the neutral position in the ID and RA groups
      before surgery was 7.8 and 7.2 mm, respectively (p > 0.74). The average ADI value
      at the flexion position in the two groups was 10.3 and 11.7 mm, respectively (p >
      0.06). The average SAC value at the neutral position in the two groups was 12.0
      and 17.1 mm, respectively (p < 0.01). Finally, the average SAC value at the
      flexion position in the two groups was 10.7 and 13.5 mm, respectively (p < 0.01).
      CONCLUSIONS: The SAC value at both the neutral and flexion positions in
      idiopathic AAS patients was significantly smaller than those values in RA-AAS
      patients. This may be because the narrowing of the SAC in the idiopathic group
      easily induces cervical myelopathy. Furthermore, surgery was often recommended to
      RA patients, because of the neck pain induced by RA-related inflammation of the
      atlanto-axial joint, regardless of any underlying myelopathy.

PMID- 22878379
TI  - From a ratchet mechanism to random fluctuations evolution of Hsp90's
      mechanochemical cycle.
AB  - The 90-kDa heat shock proteins [heat shock protein 90 (Hsp90)] are a highly
      conserved ATP-dependent protein family, which can be found from prokaryotic to
      eukaryotic organisms. In general, Hsp90s are elongated dimers with N- and C
      terminal dimerization sites. In a series of publications, we have recently shown
      that no successive mechanochemical cycle exists for yeast Hsp90 (yHsp90) in the
      absence of clients or cochaperones. Here, we resolve the mechanochemical cycle of
      the bacterial homologue HtpG by means of two- and three-color single-molecule
      FRET (Forster resonance energy transfer). Unlike yHsp90, the N-terminal dynamics
      of HtpG is strongly influenced by nucleotide binding and turnover-its reaction
      cycle is driven by a mechanical ratchet mechanism. However, the C-terminal
      dimerization site is mainly closed and not influenced by nucleotides. The direct
      comparison of both proteins shows that the Hsp90 machinery has developed to a
      more flexible and less nucleotide-controlled system during evolution.

PMID- 22878380
TI  - Disagreement among common measures of asthma control in children.
AB  - BACKGROUND: Asthma is a worldwide problem. It cannot be prevented or cured, but
      it is possible, at least in principle, to control asthma with modern management.
      Control usually is assessed by history of symptoms, physical examination, and
      measurement of lung function. A practical problem is that these measures of
      control may not be in agreement. The aim of this study was to describe agreement
      among different measures of asthma control in children. METHODS: A prospective
      sequential sample of children aged 4 to 11 years with atopic asthma attending a
      routine follow-up evaluation were studied. Patients were assessed with the
      following four steps: (1) fraction of exhaled nitric oxide (FENO), (2)
      spirometry, (3) Childhood Asthma Control Test (cACT), and (4) conventional
      clinical assessment by a pediatrician. The outcome for each test was coded as
      controlled or uncontrolled asthma. Agreement among measures was examined by cross
      tabulation and kappa statistics. RESULTS: Eighty children were enrolled, and nine
      were excluded. Mean FENO in pediatrician-judged uncontrolled asthma was double
      that of controlled asthma (37 parts per billion vs 15 parts per billion, P <
      .005). There was disagreement among measures of control. Spirometric indices
      revealed some correlation, but of the unrelated comparisons, those that agreed
      with each other most often (69%) were clinical assessment by the pediatrician and
      the cACT. Worst agreement was noted for FENO and cACT (49.3%). CONCLUSION:
      Overall, different measures to assess control of asthma showed a lack of
      agreement for all comparisons in this study.

PMID- 22878381
TI  - Effect of multizone refractive multifocal contact lenses on standard automated
      perimetry.
AB  - PURPOSE: The aim of this study was to evaluate whether the creation of 2 foci
      (distance and near) provided by multizone refractive multifocal contact lenses
      (CLs) for presbyopia correction affects the measurements on Humphreys 24-2
      Swedish interactive threshold algorithm (SITA) standard automated perimetry
      (SAP). METHODS: In this crossover study, 30 subjects were fitted in random order
      with either a multifocal CL or a monofocal CL. After 1 month, a Humphrey 24-2
      SITA standard strategy was performed. The visual field global indices (the mean
      deviation [MD] and pattern standard deviation [PSD]), reliability indices, test
      duration, and number of depressed points deviating at P<5%, P<2%, P<1%, and
      P<0.5% on pattern deviation probability plots were determined and compared
      between multifocal and monofocal CLs. RESULTS: Thirty eyes of 30 subjects were
      included in this study. There were no statistically significant differences in
      reliability indices or test duration. There was a statistically significant
      reduction in the MD with the multifocal CL compared with monfocal CL (P=0.001).
      Differences were not found in PSD nor in the number of depressed points deviating
      at P<5%, P<2%, P<1%, and P<0.5% in the pattern deviation probability maps
      studied. CONCLUSIONS: The results of this study suggest that the multizone
      refractive lens produces a generalized depression in threshold sensitivity as
      measured by the Humphreys 24-2 SITA SAP.

PMID- 22878382
TI  - Changes in accommodation and ocular aberration with simultaneous vision
      multifocal contact lenses.
AB  - OBJECTIVE: The aim of this study was to evaluate ocular aberration changes
      through different simultaneous vision multifocal contact lenses (CLs). METHODS:
      Eighteen young-adult subjects with a mean age of 29.8+/-2.11 years took part.
      Changes in accommodative response, spherical aberration (C(4)(0)), horizontal
      coma (C(3)(1)), vertical coma (C(3)(-1)), and root mean square (RMS) of higher
      order aberrations (HOAs, third to sixth orders) were evaluated. Measurements were
      obtained with a distance-single vision CL and 2 aspheric multifocal CLs of
      simultaneous focus center-near design (PureVision Low Add and PureVision High
      Add) for 2 accommodative stimuli (-2.50 and -4.00 D). All measurements were
      performed monocularly with a Hartmann-Shack aberrometer (IRX-3; Imagine Eyes,
      Orsay, France). RESULTS: No statistically significant differences were found in
      accommodative responses to -2.50- and -4.00-D stimuli between the single vision
      CL and the 2 multifocal CLs. Spherical aberration was found to decrease and
      become more negative with accommodation for both stimuli with all three CLs.
      Horizontal coma decreased significantly with accommodation (-2.5- and -4.00-D
      stimuli) for the distance-single vision CLs (P=0.002 and P=0.003). No differences
      were found in vertical coma Zernike coefficients. The RMS of HOAs was found to
      decrease only with the single vision CLs for both stimuli (P<0.01). CONCLUSIONS:
      Data obtained in this study suggest that in young subjects, the multifocal CLs
      studied do not induce large changes in accommodative response compared with the
      distance-single vision CLs. Spherical aberration reduced significantly with
      accommodation.

PMID- 22878383
TI  - Evaluation of 0.3% gatifloxacin hydrochloride in decontamination of donor
      corneas.
AB  - PURPOSE: To evaluate demographic, clinical, and microbiological profile of eye
      donors and efficacy of 0.3% gatifloxacin hydrochloride in microbial
      decontamination of donor corneas. METHODS: About 513 donors and 1,026 corneas
      received at National Eye Bank of a tertiary care hospital during 1-year period
      were analyzed prospectively in this randomized clinical trial. The donor eyes
      were graded and treated with 5% povidone-iodine, 0.4% amikacin sulphate, and 0.3%
      gatifloxacin hydrochloride. The parameters evaluated were death enucleation time
      (DET), grading of donor corneas, microbiological profile of culture organisms,
      and their sensitivity to various antibiotics. RESULTS: Mean DET was 6.29+/-5.7
      hours. Forty one percent eyes were optical grade corneas and the majority of
      donors (38.5%) had accidental deaths. Good grade eyes were maximum with DET of <1
      hour and were comparable between 0-6 hours and 6-12 hours. About 57.6% (591/1026)
      eyes were culture positive; most common organisms were Pseudomonas spp (53%) and
      Coagulase-negative Staphylococci (24%). Culture positivity reduced significantly
      after treatment with povidone iodine and amikacin (P=0.002, right eye; P=0.004;
      left eye) and decreased further with use of gatifloxacin (P=0.001). Pseudomonas
      (93%), Coagulase-negative Staphylococci (96.3%), Staphylococcus aureus (90.5%),
      enterococci and gram-negative bacilli were sensitive to gatifloxacin. Pseudomonas
      spp which were multidrug-resistant were sensitive to polymyxin-B. CONCLUSIONS:
      Gatifloxacin hydrochloride in addition to amikacin sulphate is beneficial for
      donor eye decontamination. Polymyxin-B may be used for multidrug-resistant
      Pseudomonas spp.

PMID- 22878384
TI  - Molecular basis for the maintenance of envelope integrity in Selenomonas
      ruminantium: cadaverine biosynthesis and covalent modification into the
      peptidoglycan play a major role.
AB  - Polyamine is a small organic polycation composed of a hydrocarbon backbone with
      multiple amino groups which ubiquitously exists in all living organisms from
      bacteria to higher animals. The critical step of polyamine biosynthesis generally
      includes the amino acid-decarboxylating reaction to produce the primary diamines,
      such as a synthesis of putrescine (NH(3)(+).(CH(2))(4).NH(3)(+)) from ornithine,
      and cadaverine (NH(3)(+).(CH(2))(5).NH(3)(+)) from lysine, which are catalyzed by
      pyridoxal-5'-phosphate (PLP; vitamin B(6))-dependent decarboxylases. Synthesized
      polyamines are implicated in a wide variety of cytoplasmic reactions such as DNA
      replication and protein synthesis, and are essential for proper growth of the
      organisms. However, in Selenomonas ruminantium, a strictly anaerobic Gram
      negative bacterium dominant in sheep rumen, cadaverine displays its function in a
      quite distinctive scheme compared to the general bacteria reported. It serves as
      an essential constituent of the peptidoglycan for the maintenance of envelope
      integrity through an interaction with the periplasm-exposed SLH domain of Mep45,
      the outer membrane protein of this bacterium. Furthermore, cytoplasmic
      biosynthesis of cadaverine occurs totally in a eukaryotic-like manner rather than
      in a conventional way of bacteria. Lysine/ornithine decarboxylase (LDC/ODC), a
      PLP-dependent enzyme responsible for cadaverine synthesis in this bacterium,
      displays significant homology to the eukaryotic ODC but not to the general
      bacterial LDC nor ODC, and its activity is tightly regulated by antizyme-mediated
      proteolysis, a regulatory process generally found in eukaryotes. These findings
      represent the biological diversity of this bacterium beyond the preexisting
      knowledge related to the polyamine-physiology, cell envelope-architecture, and
      the regulatory system for the enzyme. In this review we will describe (i) the
      cadaverine-containing peptidoglycan of S. ruminantium: its chemical structure,
      biosynthesis, and biological function, and (ii) cellular biosynthesis of
      cadaverine by LDC/ODC and its antizyme-mediated regulation. In addition, we will
      briefly refer to (iii) the phylogenetic position and characteristics of S.
      ruminantium and its unique cadaverine-physiology.

PMID- 22878385
TI  - Vitamin E improves biochemical indices associated with symptoms of atopic
      dermatitis-like inflammation in NC/Nga mice.
AB  - We aimed to define whether vitamin E improves biochemical indices associated with
      symptoms of atopic dermatitis-like inflammation in NC/Nga mice. After picryl
      chloride (PC) application to their backs, changes in the content of
      thiobarbituric acid reactive substances (TBARS) and vitamin E, as well as the
      activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione
      peroxidase (GSHPx) and catalase) were analyzed in the serum and skin of NC/Nga
      mice during a symptomatic cycle. The levels of inflammatory factors were also
      assessed, including IgE, cyclooxigenase-2 (COX-2), tumor necrosis factor (TNF
      alpha) and nuclear factor-kappaB (NF-kappaB). When allergic dermatitis was
      induced by the application of PC to the skin of the mice, skin inflammation
      appeared 2 wk after PC application, with the peak severity of inflammation
      observed 5 wk after PC application. Subsequently, the animals recovered from the
      inflammation by 9 wk after PC application. The TBARS content in the skin and
      serum increased markedly when the symptoms were the most severe, and decreased to
      levels near those in control mice by 9 wk after PC application. The activities of
      SOD and GSHPx in the skin and serum were also positively correlated with
      symptomatic changes; however, no change in catalase activity was observed 5 wk
      after PC application. Conversely, vitamin E content decreased at the stage of
      peak severity. The levels of all inflammatory factors analyzed in this study were
      altered in a manner similar to other indices. Additionally, vitamin E treatment
      markedly inhibited these PC-induced alterations. On the basis of these results,
      it is expected that the observed alterations in biochemical indices, which
      reflect the symptomatic cycle, may be applicable to objective diagnosis and
      treatment for atopic dermatitis, and that vitamin E may improve the symptoms of
      AD.

PMID- 22878386
TI  - Ascorbic acid levels in various tissues, plasma and urine of mice during aging.
AB  - Here we quantified ascorbic acid (AA) levels in 14 tissues, plasma and urine of
      C57BL/6 male mice to track its turnover during 3 to 30 mo of aging. The AA
      content of adrenal glands and testes decreased somewhat with age, and eventually
      rose, but increased in the spleen, lungs, eyes and heart. AA levels rose in the
      liver, skin and skeletal muscles from 6 to 12 mo of age, but declined from 12 to
      24 mo. In the cerebellum, cerebrum, small intestine, kidney and plasma, amounts
      of AA remained almost constant as the animals aged. Most notably, urinary AA
      decreased markedly until becoming almost undetectable at 24 and 30 mo of age.
      Collectively, these results, which compare changes in AA levels in specific
      physiologic targets throughout the aging process, strongly suggest that the AA
      synthesizing capacity declines over time to become a major factor in senescence
      related diseases.

PMID- 22878387
TI  - Hypolipidemic and bifidogenic potentials in the dietary fiber prepared from Mikan
      (Japanese mandarin orange: Citrus unshiu) albedo.
AB  - The albedo is the white part of the citrus peel, which acts as a water reservoir
      for the juice sacs, seeds and leaves in times of drought. As the functionality of
      the albedo is unknown, we examined in this study the hypolipidemic and
      bifidogenic potentials of dietary fiber (DF) prepared from the Mikan (Japanese
      mandarin orange: Citrus unshiu) albedo. The albedo was obtained from Mikan
      harvested in Arida, Wakayama Prefecture, and total DF (TDF), water soluble DF
      (SDF) and water insoluble DF (IDF) were extracted. Albedo TDF contained arabinose
      (37.21%), galactose (16.05%), xylose (18.30%) and glucose (13.94%), but did not
      contain detectable amounts of galacturonic acid. Albedo SDF inhibited the
      enzymatic digestion of triolein by pancreatic lipase in vitro. The SDF, at a
      concentration of 80 mg per 6 mL of substrate solution, significantly inhibited
      the activity of this enzyme (>50%). As compared to a control group on a 5%
      cellulose diet, rats fed a diet containing 1% albedo TDF for 4 wk showed
      significantly decreased serum triacylglycerol concentrations, increased fecal
      lipid excretion, and no changes in hepatic lipid content (triacylglycerol, total
      cholesterol, and phospholipid) or serum concentrations of total cholesterol or
      phospholipid. Consumption of albedo TDF also increased the number of
      bifidobacteria in the cecum. In this report, we have demonstrated that
      consumption of albedo TDF increased the levels bifidobacteria in the rat cecum,
      and decreased serum triacylglycerol concentrations due to the accelerated lipid
      excretion into the feces caused by the inhibition of pancreatic lipase.

PMID- 22878388
TI  - Associations between leukocyte counts and cardiovascular disease risk factors in
      apparently healthy Japanese men.
AB  - Increased leukocyte counts, particularly white blood cell and neutrophil counts,
      are reportedly associated with increased incidence of cardiovascular diseases
      (CVD) and mortality in subjects with acute and moderate coronary diseases.
      However, few reports have determined the associations between leukocyte subset
      (i.e., white blood cells, neutrophils, monocytes, lymphocytes, basophils and
      eosinophils) counts and CVD risk factors. In this study, we examined the
      associations between leukocyte subset counts and CVD risk factors in apparently
      healthy Japanese men. We conducted a cross-sectional study of men who
      participated in health checkups, and selected those who were not being treated
      for metabolic diseases. We determined associations between leukocyte subset
      counts and CVD risk factors by multivariate linear regression (MLR) analysis and
      analysis of covariance (ANCOVA). Overall, 3,576 subjects aged 49.3+/-5.75 (range,
      40-59) y were recruited. MLR and ANCOVA showed that white blood cell, neutrophil,
      monocyte counts are associated with decreased high-density lipoprotein
      cholesterol (HDL-C) and increased C-reactive protein levels, the lymphocyte count
      is positively associated with lipid abnormalities (i.e., decreased HDL-C,
      increased low-density lipoprotein cholesterol and increased triacylglycerol
      (TG)), and the basophil count is associated with increased TG and liver injury
      marker levels (i.e., alanine aminotransferase). Our results in this study
      demonstrated that leukocyte subset counts showed differential associations with
      CVD risk factors in apparently healthy Japanese men.

PMID- 22878389
TI  - Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum
      extract on carbon tetrachloride-induced acute hepatic injury in mice.
AB  - The present study aims to evaluate the anti-HCV activity of hotwater extract from
      Platycodon grandiflorum (BC703) with HCV genotype 1b subgenomic replicon system
      and investigate its hepatoprotective activity on carbon tetrachloride (CCl(4))
      induced acute liver damage in mice. BC703 produced significant hepatoprotective
      effects against CCl(4)-induced acute hepatic injury by decreasing the activities
      of serum enzymes, nitric oxide and lipid peroxidation. Histopathological studies
      further substantiated the protective effect of BC703. Furthermore, BC703
      inhibited the HCV RNA replication with an EC(50) value and selective index
      (CC(50)/EC(50)) of 2.82 ug/mL and above 35.46, respectively. However, digested
      BC703 using a simulated gastric juice showed poor protective effect against
      CCl(4)-induced hepatotoxicity in mice and decreased anti-HCV activity as compared
      to the intact BC703. Although further studies are necessary, BC703 may be a
      beneficial agent for the management of acute hepatic injury and chronic HCV
      infection.

PMID- 22878390
TI  - Administration of dried Aloe vera gel powder reduced body fat mass in diet
      induced obesity (DIO) rats.
AB  - The aim of the present study was to investigate the anti-obesity effects of Aloe
      vera gel administration in male Sprague-Dawley (SD) rats with diet-induced
      obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal%
      fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period.
      Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered
      with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body
      weights (g) and body fat (%) of HFD fed rats were significantly higher than those
      of StdD-fed rats. Although a modest decrease of body weight (g) was observed with
      the administration of dried Aloe vera gel powder, both subcutaneous and visceral
      fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel
      treated rats. Serum lipid parameters elevated by HFD were also improved by the
      Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy
      expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats.
      Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats.
      These results suggest that intake of Aloe vera gel reduced body fat accumulation,
      in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial
      for the prevention and improvement of diet-induced obesity.

PMID- 22878391
TI  - Puerarin exerted anti-osteoporotic action independent of estrogen receptor
      mediated pathway.
AB  - Puerarin, a daidzein-8-C glucoside, is the major isoflavonoid in Kudzu (Pueraria
      lobata), and is unique in that it contains C-C conjugated glucose at position 8
      of the isoflavonoid structure. A puerarin diet at a dose of 5 mg/kg b.w./d to fed
      ovariectomized mice for 2 mo diminished the urinary deoxypyridinoline, a typical
      bone-degradation product. Since the bone absorption marker, serum tartarate
      resistant acid phosphatase (TRAP) activity of puerarin-fed mice decreased but the
      bone formation marker, osteocalcin level, did not alter, the puerarin diet was
      proved to specifically depress the bone absorption, but not the overall bone
      metabolism. In accordance with that results, the femur structure of puerarin-fed
      mice was restored compared with that of puerarin-free diet mice. The atrophied
      uterine due to low estrogen (E2) level after ovariectomy was not restored by the
      puerarin diet, suggesting that puerarin exerted the anti-osteoporotic action
      through a non estrogen receptor (ER) mediated-pathway, in vivo. The growth of an
      ER-positive human breast cancer cell, MCF-70, was not enhanced by puerarin,
      suggesting that puerarin did not show estrogen-like action on MCF-7 cells, even
      at a ten thousand times higher concentration than that of E2. Furthermore,
      ICI182,780 (ICI), an estrogen antagonist, suppressed the enhanced growth of MCF-7
      cells by E2, but not that by puerarin. In an ER-binding assay, puerarin was
      proved not to bind to ERalpha or beta, or if all, extremely weakly, although
      daidzein, an aglycon of puerarin, showed a little stronger binding compared with
      puerarin. All these results strongly indicate that puerarin exerts its anti
      osteoprotic action independently of the ER-mediated pathway.

PMID- 22878392
TI  - A cross-investigation between thiamin deficiency and the physical condition of
      elderly people who require nursing care.
AB  - In recent years the occurrence of thiamin deficiency diseases has increased
      particularly among elderly people and there has been some speculation about
      whether or not any particular factors exist. In this study, we focused on elderly
      people requiring constant care in nursing homes and we conducted an accurate
      condition survey of total thiamin concentration in whole blood as a means of
      nutritional assessment. The total number of participants was 14 males and 60
      females who were residing in a nursing home; they were aged between 65 and 105 y
      old. All of the subjects agreed to take part in our research. We conducted the
      following tests: anthropometric measurements, blood examination including total
      thiamin levels, and also physical functions such as in the level of nursing care
      required and tests of other physical conditions. The average+/-standard deviation
      of thiamin concentration was 22.4+/-8.9 ng/mL and the number of people with a
      deficient condition (less than 20 ng/mL) was 42, which was 56.8% of the total.
      From these results, the existence of thiamin deficiency is validated in more than
      half of the elderly people who require nursing care. On the other hand, the
      method of meal intake for all participants who have a thiamin deficiency was oral
      intake and for those who were non-deficient in thiamin, the percentage of tube
      feeding or nutritional supplementation intravenously was 37.5%, which was a
      significantly high value.

PMID- 22878393
TI  - Digestive enzyme inhibitors from grains as potential components of
      nutraceuticals.
AB  - Inhibitor activity against digestive enzymes, such as alpha-amylase from human
      saliva and porcine pancreas and trypsin from bovine pancreas, of three cereal
      grains species were studied as potential components of nutraceuticals
      strengthening diabetes and obesity treatment. Significant differences were
      demonstrated: the highest antitryptic activity was found in the grain of the rye
      varieties studied, whereas the grain of the wheat varieties had significantly
      higher ability to inhibit alpha-amylases from human saliva and porcine pancreas.
      Additionally, seeds of Puma, one of the studied wheat varieties, demonstrated
      especially low antitryptic activity. Such a beneficial arrangement of inhibitors,
      i.e. high level of inhibitors of alpha-amylase from human saliva and porcine
      pancreas and simultaneously low level of trypsin inhibitors from bovine pancreas,
      indicate the possibility of the application of seeds with such properties to the
      preparation of nutraceuticals for people with obesity or suffering from diabetes.

PMID- 22878394
TI  - The hydrophobic core of FliG domain II is the stabilizer in the Salmonella
      flagellar motor.
AB  - The flagellar protein FliG is the major component of the flagellar torque
      generator, and consists of two separate domains, I and II. Domain I is essential
      for flagellar assembly, while domain II in the C-terminal region is not essential
      for flagellar assembly but is dedicated to torque generation. Previously, we
      found that some fliG mutants were temperature-hypersensitive (hyper-TS) and
      identified three residues (F236V, D244Y and K273E) on domain II responsible for
      the temperature-sensitive (TS) phenotype. In this study, we substituted the three
      residues with all 20 amino acids (X) and analysed the behaviour of the variants
      at various temperatures. Each group of F236X, D244X and K273X variants gave rise
      to several hyper-TS mutants. In F236X, only substitution with F and W gave rise
      to wild-type, while other hydrophobic residues resulted in hyper-TS mutants and
      hydrophilic residues resulted in non-motile variants. The atomic arrangement
      around the F236 residue indicated that F236 together with neighbouring residues
      forms a hydrophobic core in the centre of domain II, which is well conserved
      among many species. These data suggest that the hydrophobic core may play an
      essential role in stabilizing the whole structure of domain II, so that changes
      of physiological conditions in the microenvironment of domain II do not perturb
      torque generation.

PMID- 22878395
TI  - Aerobic glycerol dissimilation via the Enterococcus faecalis DhaK pathway depends
      on NADH oxidase and a phosphotransfer reaction from PEP to DhaK via EIIADha.
AB  - Two pathways for glycerol dissimilation are present in Enterococcus faecalis.
      Either glycerol is first phosphorylated by glycerol kinase and then oxidized by
      glycerol-3-phosphate oxidase with molecular oxygen as the electron acceptor
      (GlpO/GlpK pathway), or it is first oxidized by glycerol dehydrogenase with
      NAD(+) as the acceptor of the reduction equivalents and then phosphorylated by
      dihydroxyacetone kinase (GldA/DhaK pathway). The final end product in both cases
      is dihydroxyacetone phosphate (DHAP). The genes of the GldA/DhaK pathway are
      present in a four-gene operon structure encoding GldA, a small hypothetical
      protein (EF1359), and two subunits of dihydroxyacetone kinase (DhaK and DhaL). We
      demonstrate in this study that protein EF1359 is part of a phosphorylation
      cascade which phosphorylates dihydroxyacetone in a phosphoenolpyruvate (PEP)
      dependent reaction via EI, HPr, EF1359 and DhaLK. Furthermore we show that
      aerobic dissimilation of glycerol via the GldA/DhaK pathway is dependent on
      active NADH oxidase to regenerate NADH in Ent. faecalis. A refined model of the
      aerobic metabolism of glycerol via the GldA/DhaK pathway is presented.

PMID- 22878396
TI  - Development of a high- versus low-pathogenicity model of the free-living amoeba
      Naegleria fowleri.
AB  - Species in the genus Naegleria are free-living amoebae of the soil and warm fresh
      water. Although around 30 species have been recognized, Naegleria fowleri is the
      only one that causes primary amoebic meningoencephalitis (PAM) in humans. PAM is
      an acute and fast progressing disease affecting the central nervous system. Most
      of the patients die within 1-2 weeks of exposure to the infectious water source.
      The fact that N. fowleri causes such fast progressing and highly lethal
      infections has opened many questions regarding the relevant pathogenicity factors
      of the amoeba. In order to investigate the pathogenesis of N. fowleri under
      defined experimental conditions, we developed a novel high- versus low
      pathogenicity model for this pathogen. We showed that the composition of the
      axenic growth media influenced growth behaviour and morphology, as well as in
      vitro cytotoxicity and in vivo pathogenicity of N. fowleri. Trophozoites
      maintained in Nelson's medium were highly pathogenic for mice, demonstrated rapid
      in vitro proliferation, characteristic expression of surface membrane vesicles
      and a small cell diameter, and killed target mouse fibroblasts by both contact
      dependent and -independent destruction. In contrast, N. fowleri cultured in PYNFH
      medium exhibited a low pathogenicity, slower growth, increased cell size and
      contact-dependent target cell destruction. However, cultivation of the amoeba in
      PYNFH medium supplemented with liver hydrolysate (LH) resulted in trophozoites
      that were highly pathogenic in mice, and demonstrated an intermediate
      proliferation rate in vitro, diminished cell diameter and contact-dependent
      target cell destruction. Thus, in this model, the presence of LH resulted in
      increased proliferation of trophozoites in vitro and enhanced pathogenicity of N.
      fowleri in mice. However, neither in vitro cytotoxicity mechanisms nor the
      presence of membrane vesicles on the surface correlated with the pathologic
      potential of the amoeba. This indicated that the pathogenicity of N. fowleri
      remains a complex interaction between as-yet-unidentified cellular mechanisms.

PMID- 22878397
TI  - Sensitivity of pathogenic and commensal bacteria from the human colon to
      essential oils.
AB  - The microbiota of the intestinal tract plays an important role in colonic health,
      mediating many effects of dietary components on colonic health and during enteric
      infections. In the context of the increasing incidence of antibiotic resistance
      in gut bacteria, complementary therapies are required for the prevention and
      treatment of enteric infections. Here we report the potential application of
      essential oils (EO) and pure EO compounds to improve human gut health. Nerolidol,
      thymol, eugenol and geraniol inhibited growth of the pathogens Escherichia coli
      O157 : H7(VT(-)), Clostridium difficile DSM1296, Clostridium perfringens
      DSM11780, Salmonella typhimurium 3530 and Salmonella enteritidis S1400 at a half
      maximal inhibitory concentration (IC(50)) varying from 50 to 500 p.p.m. Most EO
      showed greater toxicity to pathogens than to commensals. However, the beneficial
      commensal Faecalibacterium prausnitzii was sensitive to EO at similar or even
      lower concentrations than the pathogens. The EO showed dose-dependent effects on
      cell integrity, as measured using propidium iodide, of Gram-positive bacteria.
      These effects were not strongly correlated with growth inhibition, however,
      suggesting that cell membrane damage occurred but was not the primary cause of
      growth inhibition. Growth inhibition of Gram-negative bacteria, in contrast,
      occurred mostly without cell integrity loss. Principal component analysis showed
      clustering of responses according to bacterial species rather than to the
      identity of the EO, with the exception that responses to thymol and nerolidol
      clustered away from the other EO. In conclusion, the selective effects of some EO
      might have beneficial effects on gut health if chosen carefully for effectiveness
      against different species.

PMID- 22878398
TI  - Is retirement beneficial or harmful to mental health?

PMID- 22878399
TI  - Clonal analysis of the quasispecies of antiviral-resistant HBV genomes in
      patients with entecavir resistance during rescue treatment and successful
      treatment of entecavir resistance with tenofovir.
AB  - BACKGROUND: Clonal analysis of quasispecies of resistant HBV genomes in patients
      with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV)
      rescue therapy has never been performed. METHODS: A sample of 10 patients with
      ETV resistance who were switched to 3TC+ADV treatment were analysed for changes
      in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of
      3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per
      sample (total 1,068 clones, mean 63) were sequenced. RESULTS: 3TC+ADV therapy led
      to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC
      resistance mutations before and during combination therapy. All clones had >=1 of
      the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The
      percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV
      mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with
      detectable HBV DNA (median 5.17 log(10) copies/ml) after a median 24 months of
      ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months
      of treatment. CONCLUSIONS: In patients with ETV resistance tenofovir is
      effective. Clonal analysis data indicate no selection of specific HBV mutants
      during rescue 3TC+ADV.

PMID- 22878400
TI  - The thyroid axis is regulated by NCoR1 via its actions in the pituitary.
AB  - TSH is the most important biomarker in the interpretation of thyroid function in
      man. Its levels are determined by circulating thyroid hormone (TH) levels that
      feed back centrally to regulate the expression of the subunits that comprise TSH
      from the pituitary. The nuclear corepressor 1 (NCoR1), is a critical coregulator
      of the TH receptor (TR) isoforms. It has been established to play a major role in
      the control of TSH secretion, because mice that express a mutant NCoR1 allele
      (NCoRDeltaID) that cannot interact with the TR have normal TSH levels despite low
      circulating TH levels. To determine how NCoR1 controls TSH secretion, we first
      developed a mouse model that allowed for induction of NCoRDeltaID expression
      postnatally to rule out a developmental effect of NCoR1. Expression of
      NCoRDeltaID postnatally led to a drop in TH levels without a compensatory rise in
      TSH production, indicating that NCoR1 acutely controls both TH production and
      feedback regulation of TSH. To demonstrate that this was a cell autonomous
      function of NCoR1, we expressed NCoRDeltaID in the pituitary using a Cre driven
      by the glycoprotein alpha-subunit promoter (P-DeltaID mice). Importantly, P
      DeltaID mice have low TH levels with decreased TSH production. Additionally, the
      rise in TSH during hypothyroidism is blunted in P-DeltaID mice. Thus, NCoR1 plays
      a critical role in TH-mediated regulation of TSH in the pituitary by regulating
      the repressive function of the TR. Furthermore, these studies suggest that
      endogenous NCoR1 levels in the pituitary could establish the set point of TSH
      secretion.

PMID- 22878401
TI  - Hypoxia induces autophagy in primary human trophoblasts.
AB  - Autophagy is a highly regulated and dynamic process that maintains cellular
      homeostasis and plays a prosurvival role in most cells. Although hypoxia has been
      shown to induce apoptosis in placental trophoblasts, the hypoxic effect on
      autophagy has not been studied. We hypothesized that autophagy plays a
      prosurvival role in the placental trophoblasts by antagonizing hypoxia-induced
      apoptosis. Our data show that the expression of Light chain 3-II (LC3-II), an
      autophagic marker and cleaved poly(ADP-ribose) polymerase, an apoptosis marker,
      are inversely related in cultured trophoblasts. Exposure to rapamycin or hypoxia
      inactivated mammalian target of rapamycin, as reflected by reduced
      phosphorylation of ribosomal protein S6, indicating that mammalian target of
      rapamycin regulates autophagy in cultured cytotrophoblasts. Bafilomycin prevented
      the degradation of cargo and increased LC3-II and p62 in cytotrophoblasts exposed
      to hypoxia, revealing enhanced autophagic flux. Importantly, bafilomycin enhanced
      expression of autophagy-related protein 7 (Atg7), parallel to the increased
      apoptosis measured by cleaved poly(ADP-ribose) polymerase. LY294002, a
      phosphatidylinositol 3-kinase inhibitor, increased apoptosis in the trophoblasts
      under hypoxia or standard conditions. Silencing of Atg7 decreased both apoptosis
      and LC3-II in the trophoblasts, suggesting a dual role of Atg7 in both autophagy
      and apoptosis. We conclude that there is a cross talk between autophagy and
      apoptosis in the placental trophoblasts; autophagy plays a prosurvival role and
      Atg7 has roles in both autophagy and apoptosis under hypoxia.

PMID- 22878402
TI  - Task3 potassium channel gene invalidation causes low renin and salt-sensitive
      arterial hypertension.
AB  - Task1 and Task3 potassium channels (Task: tandem of P domains in a weak inward
      rectifying K(+) channel-related acid-sensitive K(+) channel) are believed to
      control the membrane voltage of aldosterone-producing adrenal glomerulosa cells.
      This study aimed at understanding the role of Task3 for the control of
      aldosterone secretion. The adrenal phenotype of Task3(-/-) mice was investigated
      using electrophysiology, adrenal slices, and blood pressure measurements. Primary
      adrenocortical cells of Task3(-/-) mice were strongly depolarized compared with
      wild-type (-52 vs. -79 mV), and in fresh adrenal slices Ca(2+) signaling of
      Task3(-/-) glomerulosa cells was abnormal. In living Task3(-/-) mice, the
      regulation of aldosterone secretion showed specific deficits: Under low Na(+) and
      high K(+) diets, protocols known to increase aldosterone, and under standard
      diet, Task3 inactivation was compensated and aldosterone was normal. However,
      high Na(+) and low K(+) diets, two protocols known to lower aldosterone, failed
      to lower aldosterone in Task3(-/-) mice. The physiological regulation of
      aldosterone was disturbed: aldosterone-renin ratio, an indicator of autonomous
      aldosterone secretion, was 3-fold elevated at standard and high Na(+) diets.
      Isolated adrenal glands of Task3(-/-) produced 2-fold more aldosterone. As a
      consequence, Task3(-/-) mice showed salt-sensitive arterial hypertension (plus 10
      mm Hg). In conclusion, Task3 plays an important role in the adaptation of
      aldosterone secretion to dietary salt intake.

PMID- 22878403
TI  - Combination evaluation of preoperative risk indices predicts requirement of
      biventricular assist device.
AB  - BACKGROUND: Patients with biventricular assist device (BiVAD) placement have a
      poor prognosis, but preoperative risk factors for the necessity of BiVAD have not
      been fully elucidated. METHODS AND RESULTS: Data from 79 patients who received
      left ventricular assist device (LVAD) between November 2002 and December 2011
      were retrospectively reviewed. Overall, 9 patients (11.4%) required BiVAD, and
      the survival rate of BiVAD patients was significantly lower than that of LVAD
      patients (P<0.001). Multivariate analysis for BiVAD requirement showed left
      ventricular diastolic diameter (LVDd) <=62 mm (odds ratio [OR], 10.97; P=0.009)
      to be significantly associated with BiVAD requirement. Preoperative central
      venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio >=0.5 (OR,
      13.09; P=0.028) was also significantly associated with BiVAD requirement. A new
      scoring system for predicting BiVAD requirement was created from the combination
      of CVP/PCWP ratio (>=0.5), body surface area (<=1.4 m(2)), preoperative
      continuous hemodiafiltration use, B-type natriuretic peptide (>=1,200 pg/ml) and
      LVDd (<=62 mm), and this had a significantly larger area under the curve (0.909;
      P=0.003) than right ventricular stroke work index on receiver operating
      characteristic analysis. A score >20 using the new scoring method indicated
      significantly high probability of BiVAD requirement (OR, 16.00; P=0.019).
      CONCLUSIONS: The new scoring method, which includes CVP/PCWP ratio, is a novel
      risk stratification tool for BiVAD therapy.

PMID- 22878404
TI  - Evaluation of left ventricular diastolic function after valve replacement in
      aortic stenosis using exercise Doppler echocardiography.
AB  - BACKGROUND: The aim of the present study was to evaluate the mechanism of
      diastolic dysfunction (DD) after aortic valve replacement (AVR) in patients with
      aortic stenosis (AS). METHODS AND RESULTS: Supine bicycle exercise Doppler
      echocardiography (EDE) with measurement of early diastolic peak velocities of
      transmitral flow (E) and mitral septal annular movement (E') was performed in 38
      patients with AS at least 24 months after AVR and in 19 sex- and age-matched
      normal controls. AS patients had a 27.4+/-32.7% decrease in the ratio of left
      ventricular (LV) mass index to LV end-diastolic volume index (LVMI/LVEDVI) after
      AVR. Pre-AVR E' was significantly lower in AS patients (4.3+/-1.6 cm/s vs. 7.7+/
      1.6 cm/s, P<0.005), resulting in a higher E/E' (16.7+/-5.4 vs. 9.3+/-1.8,
      P<0.001). E/E' at rest did not change significantly after AVR. Both E and E'
      increased progressively with exercise, and the increase in E' (P<0.001) but not E
      (P=0.675) was greater in normal controls than in AS patients (P<0.001). Peak E/E'
      >13 during EDE was more common in AS patients than in controls (89.5%, 34/39 vs.
      0%, 0/19, P<0.001). On multivariate analysis, LVMI/LVEDVI (Y=8.703+4.199X,
      r=0.433, P=0.001) was the only factor associated with peak E/E' during EDE.
      CONCLUSIONS: Persistent DD is present after AVR, due primarily to failure in
      normal physiologic augmentation of LV relaxation during exercise, associated with
      incomplete or inadequate regression of LV hypertrophy.

PMID- 22878405
TI  - Effects of pitavastatin on cardiac structure and function and on prevention of
      atrial fibrillation in elderly hypertensive patients: a prospective study of 2
      years' follow-up.
AB  - BACKGROUND: The aim of this prospective study was to determine whether statin
      therapy (pitavastatin) has a beneficial effect on the prevention of new-onset
      atrial fibrillation (AF) in elderly patients with hypertension (HTN) and to
      evaluate the relationships among statin treatment, the development of AF, and
      left atrial (LA) and ventricular (LV) structure and function. METHODS AND
      RESULTS: We enrolled eligible elderly patients (>=65 years old) with HTN and LV
      hypertrophy until the number of patients reached 110 in both groups. The 110
      patients with HTN who needed statin therapy (HTN with statin group) were started
      on pitavastatin (1-2 mg/day), and both groups continued with appropriate
      medication for HTN. LV and LA structure and function were examined by
      conventional and speckle-tracking echocardiography at baseline and after 1 year.
      LA volume and function in the HTN with statin group improved more than in the HTN
      without statin group. There was a significant difference in survival free of new
      onset AF in the patients with and without statin therapy during the 2-year follow
      up (hazard ratio: 0.32, P=0.027). CONCLUSIONS: Pitavastatin had a beneficial
      effect on LV diastolic function and LA structure and function in elderly patients
      with HTN. Pitavastatin treatment may be associated with a lower incidence of new
      onset AF.

PMID- 22878406
TI  - Prospective study on waist circumference and risk of all-cause and cardiovascular
      mortality: pooled analysis of Japanese community-based studies.
AB  - BACKGROUND: The aim of the present study was to clarify the association between
      waist circumference and all-cause and cardiovascular disease (CVD) mortality risk
      in relatively lean Japanese subjects. METHODS AND RESULTS: A total of 3,554 men
      and 4,472 women who had no history of CVD were examined and their waist
      circumference measured at baseline. The subjects were aged >=40 years and were
      obtained from 3 prospective cohort studies during 1988-1996. Hazard ratios for
      all-cause and CVD mortality were analyzed over a follow-up period of 14.7 years
      using a Cox proportional hazards model and penalized spline method, after
      adjustment for study cohort, age, smoking, alcohol drinking, hypertension,
      dyslipidemia, and diabetes. Compared with the lowest quintile, the highest
      quintile of waist circumference in men was associated with a linear reduction in
      all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95%
      confidence interval: 0.60-0.89; P for trend=0.001). CVD mortality risk was
      increased in men aged <=65 years with a higher waist circumference. This
      relationship was U-shaped. Waist circumference was not associated with all-cause
      or CVD mortality risk in women. CONCLUSIONS: Waist circumference was associated
      inversely with increased risk of all-cause death in men, but not in women. Middle
      aged men with a greater waist circumference potentially have an increased risk of
      CVD mortality.

PMID- 22878407
TI  - Atorvastatin accelerates both neointimal coverage and re-endothelialization after
      sirolimus-eluting stent implantation in a porcine model: new findings from
      optical coherence tomography and pathology.
AB  - BACKGROUND: Delayed vessel healing after drug-eluting stent implantation is
      thought to be the underlying mechanisms of late stent thrombosis (LST). METHODS
      AND RESULTS: In the animal model of stenting, 45 minipigs were divided into 3
      groups (n=15 each): bare metal stent (BMS), sirolimus-eluting stent (SES), and
      SES plus atorvastatin treatment (SES+ator). Neointimal coverage and endothelium
      coverage were evaluated separately by optical coherence tomography (OCT),
      pathology, and scanning electron microscopy (SEM) at days 7, 14 and 28. OCT
      showed that SES significantly delayed neointimal coverage compared with BMS and
      the percentage of uncovered struts in the SES+ator group was significantly
      decreased on days 7 (42.7+/-1.3% vs. 56.8+/-5.7%, P<0.01) and 14 (24.8+/-4.3% vs.
      45.3+/-2.8%, P<0.01) compared with the SES group. However, re-endothelialization
      was even more seriously delayed than neointima formation after SES deployment
      (P<0.05). Pathology and SEM revealed improved re-endothelialization of the
      neointima with atorvastatin therapy in terms of more struts covered by
      endothelium, less platelet adhesion, and higher endothelial nitric oxide synthase
      expression of the endothelial cells in the SES+ator group. Flow cytometry
      illustrated that the SES+ator group had more mobilized endothelial progenitor
      cells (EPCs) compared with the SES group at day 7 (0.21+/-0.02% vs. 0.11+/-0.03%,
      P=0.022). CONCLUSIONS: Atorvastatin pretreatment can accelerate both neointimal
      coverage and re-endothelialization after SES implantation, which may be mediated
      by the mobilization of EPC and enhancement of the endothelial function of the
      neointima.

PMID- 22878408
TI  - Rates of coronary intervention due to de novo significant atherosclerosis and
      cardiac death are very low in Korean patients with vasospastic angina: 36-month
      follow-up results of the Vasospastic Angina in the Catholic Medical Center (VA
      CMC) registry.
AB  - BACKGROUND: The rate of percutaneous coronary intervention (PCI) due to the
      development of significant atherosclerosis and the cardiac mortality rate in
      Korean patients with vasospastic angina (VSA) was estimated. METHODS AND RESULTS:
      A total of 831 patients with VSA from 8 centers were registered in the
      Vasospastic Angina in the Catholic Medical Center (VA-CMC) registry. Their
      provocation tests for VSA showed positive results. The patients with significant
      atherosclerosis (>50% luminal narrowing) on the baseline angiography were
      excluded. Subjects were VSA patients without significant atherosclerosis. A total
      of 745 patients were included in the final analysis. The mean follow-up duration
      was 36.1+/-9.8 months. The PCI rate was 2.01% (15/745). Current smoking (odds
      ratio: 2.31, P<0.05) and high levels of baseline high-sensitivity C-reactive
      protein (hsCRP) (odds ratio: 1.57, P<0.05) were independent risk factors for PCI.
      The mortality rate was 2.55% (19/745). Eleven patients died of cardiac causes
      (1.48%). Cessation of medication was an independent risk factor for cardiac
      mortality (odds ratio: 1.47, P<0.05). The mean duration from the diagnosis to the
      cardiac deaths was 10.6+/-4.3 months. CONCLUSIONS: Korean patients with VSA
      demonstrated low rates of development of significant atherosclerosis leading to
      PCI and cardiac mortality. However, cessation of medication, smoking, and high
      baseline hsCRP were the independent risk factors for unfavorable outcomes.

PMID- 22878410
TI  - Using an electronic clinical decision support system to reduce the risk of
      epidural hematoma.
AB  - Epidural hematoma is a major complication that can occur when neuraxial
      anesthesia is used concurrently with newer anticoagulation and antiplatelet
      medications. In complex hospital environments, the opportunity of performing a
      neuraxial procedure in an anticoagulated patient or starting potent
      anticoagulants on a patient with existing epidural catheter still exists. We
      describe a technique to use an electronic clinical decision support ordering
      system that helps reduce this risk of epidural hematoma. Through a series of
      automated warnings that bring to light existing anticoagulant or antiplatelet
      medications at the time of doing the procedure or a secondary warning system to
      those practitioners initiating anticoagulant medications on a patient with an
      existing epidural, we hope to reduce the number of medication errors. Before
      initiating the alert system, we had 26 events noted in the medical chart over a 3
      month period. We noted only 11 events after the initiation of the new alert
      systems and clinical decision support in a similar 3-month period. Using
      electronic clinical decision support systems can help reduce medication errors
      related to neuraxial anesthesia and anticoagulation medications in a large
      hospital system. 

PMID- 22878409
TI  - Etiology of Syncope in Patients Hospitalized With Syncope and Predictors of
      Mortality and Readmission for Syncope at 17-Month Follow-Up: A Prospective Study.
AB  - We investigated the etiologies of syncope and risk factors for mortality and
      rehospitalization for syncope at 17-month follow-up in a prospective study of 242
      consecutive patients, mean age 69 years, hospitalized for syncope. The etiologies
      of syncope included the following: vasovagal syncope in 49 patients (20%), volume
      depletion in 39 patients (16%), orthostatic hypotension in 13 patients (5%),
      primary cardiac arrhythmias in 25 patients (10.3%), structural cardiac disease in
      6 patients (2%), and drug overdose in 5 patients (2%). The etiology of syncope
      could not be determined in 84 patients (35%). Of the 242 patients, 6 (2%) were
      rehospitalized for syncope and 12 (5%) died. Stepwise logistic regression
      analysis showed that the significant independent prognostic factors for
      rehospitalization for syncope were drug overdose [odds ratio (OR): 11.506; 95%
      confidence interval (CI): 1.083-22.261]. Stepwise logistic regression analysis
      showed that significant independent prognostic factors for time to mortality were
      undetermined etiology of syncope (OR: 4.665; 95% CI: 1.002, 21.727), San
      Francisco Syncope Score (OR: 3.537; 95% CI: 1.472-8.496), hypertension (OR:
      0.099; 95% CI: 0.019-0.504), and glomerular filtration rate (OR: 0.964; 95% CI:
      0.937-0.993). 

PMID- 22878411
TI  - Acute inflammation induces insulin-like growth factor-1 to mediate Bcl-2 and
      Muc5ac expression in airway epithelial cells.
AB  - Generally, exposure to LPS in human airways occurs in the form of aerosols and
      causes an acute inflammatory response or exacerbates existing chronic
      inflammatory conditions by enhancing airway remodeling and associated
      pathologies. The present study evaluated which inflammatory mediators may be
      responsible for the expression of Bcl-2 and mucus cell metaplasia when mice are
      exposed to aerosolized LPS. At 3 days after exposure, aerosolized LPS (for 20-40
      min) with the estimated lung deposited dosage of 0, 0.02, 0.2, 1.4, and 20.2 MUg
      showed a characteristic dose-dependent increase in polymorphonuclear neutrophils.
      Significant increases of proinflammatory mediators, including IL-1beta, TNF
      alpha, IL-6, growth-related oncogene or keratinocyte-derived cytokine, IFN-gamma
      induced protein-10, monocyte chemotactic protein-1, and macrophage inflammatory
      protein-1alpha, were detected at the highest doses. In addition to increased
      numbers of airway epithelial cells, mucus cell numbers and mucus production were
      increased in a dose-dependent manner. Hyperplastic epithelial cells expressed
      insulin-like growth factor (IGF)-1 and, similar to previous studies, increased
      expression of the prosurvival protein Bcl-2 and induced expression of Muc5ac.
      Suppression of IGF-1 expression using retroviral shRNA blocked Bcl-2 expression
      in human and murine airway epithelial cells and Muc5ac in primary murine airway
      epithelial cells. These findings show that acute inflammation induces IGF-1 to
      mediate Bcl-2 and Muc5ac expression in airway epithelial cells.

PMID- 22878412
TI  - Prolonged injury and altered lung function after ozone inhalation in mice with
      chronic lung inflammation.
AB  - Surfactant protein-D (Sftpd) is a pulmonary collectin important in down
      regulating macrophage inflammatory responses. In these experiments, we analyzed
      the effects of chronic macrophage inflammation attributable to loss of Sftpd on
      the persistence of ozone-induced injury, macrophage activation, and altered
      functioning in the lung. Wild-type (Sftpd(+/+)) and Sftpd(-/-) mice (aged 8 wk)
      were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage
      (BAL) fluid and tissue were collected 72 hours later. In Sftpd(-/-) mice, but not
      Sftpd(+/+) mice, increased BAL protein and nitrogen oxides were observed after
      ozone inhalation, indicating prolonged lung injury and oxidative stress.
      Increased numbers of macrophages were also present in BAL fluid and in histologic
      sections from Sftpd(-/-) mice. These cells were enlarged and foamy, suggesting
      that they were activated. This conclusion was supported by findings of increased
      BAL chemotactic activity, and increased expression of inducible nitric oxide
      synthase in lung macrophages. In both Sftpd(+/+) and Sftpd(-/-) mice, inhalation
      of ozone was associated with functional alterations in the lung. Although these
      alterations were limited to central airway mechanics in Sftpd(+/+) mice, both
      central airway and parenchymal mechanics were modified by ozone exposure in
      Sftpd(-/-) mice. The most notable changes were evident in resistance and
      elastance spectra and baseline lung function, and in lung responsiveness to
      changes in positive end-expiratory pressure. These data demonstrate that a loss
      of Sftpd is associated with prolonged lung injury, oxidative stress, and
      macrophage accumulation and activation in response to ozone, and with more
      extensive functional changes consistent with the loss of parenchymal integrity.

PMID- 22878413
TI  - Multidirectional differentiation of Achaete-Scute homologue-1-defined progenitors
      in lung development and injury repair.
AB  - Multiple cells contribute to the function of lungs. Pulmonary neuroendocrine
      cells (PNECs) are important for the regulation of breathing and carcinogenesis,
      although they represent only a small population of the airway lining. Achaete
      Scute homologue-1 (Ascl1), a proneural basic helix-loop-helix transcription
      factor, is critical for the development of PNECs. We postulated that Ascl1
      defined cells (ASDCs) may be progenitors, and traced their fate during
      development and injury repair. R26R-stop-lacZ (Rosa) reporter mice were crossed
      with Ascl1-Cre or Ascl1-CreERTM mice, in which the Ascl1 promoter drives the
      expression of Cre or inducible Cre recombinase, respectively. ASDCs and their
      descendants will be permanently labeled. The labeled cells were characterized by
      immunohistochemistry, using highly specific differentiation markers. Lineage
      studies revealed a population that proliferates before the pseudoglandular stage,
      and widely contributes to different compartments. When ASDCs were labeled on
      Embryonic Day 9.5, they gave rise to both airway and alveolar cells, but when
      labeled on Embryonic Day 11.5, they only gave rise to airway cells. In postnatal
      naphthalene injury, ASDCs contributed to regenerating Clara cells. In conclusion,
      Ascl1-defined cells in the lung represent a novel multipotent lineage, indicating
      a close relationship of neuroendocrine cells with other cell types.

PMID- 22878414
TI  - Cytosolic thioredoxin system facilitates the import of mitochondrial small Tim
      proteins.
AB  - Thiol-disulphide redox regulation has a key role during the biogenesis of
      mitochondrial intermembrane space (IMS) proteins. Only the Cys-reduced form of
      precursor proteins can be imported into mitochondria, which is followed by
      disulphide bond formation in the mitochondrial IMS. In contrast to the wealth of
      knowledge on the oxidation process inside mitochondria, little is known about how
      precursors are maintained in an import-competent form in the cytosol. Here we
      provide the first evidence that the cytosolic thioredoxin system is required to
      maintain the IMS small Tim proteins in reduced forms and facilitate their
      mitochondrial import during respiratory growth.

PMID- 22878415
TI  - Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential,
      non-catalytic functions.
AB  - Isopeptidases are essential regulators of protein ubiquitination and sumoylation.
      However, only two families of SUMO isopeptidases are at present known. Here, we
      report an activity-based search with the suicide inhibitor haemagglutinin (HA)
      SUMO-vinylmethylester that led to the identification of a surprising new SUMO
      protease, ubiquitin-specific protease-like 1 (USPL1). Indeed, USPL1 neither binds
      nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in
      cells. C13orf22l--an essential but distant zebrafish homologue of USPL1--also
      acts on SUMO, indicating functional conservation. We have identified invariant
      USPL1 residues required for SUMO binding and cleavage. USPL1 is a low-abundance
      protein that colocalizes with coilin in Cajal bodies. Its depletion does not
      affect global sumoylation, but causes striking coilin mislocalization and impairs
      cell proliferation, functions that are not dependent on USPL1 catalytic activity.
      Thus, USPL1 represents a third type of SUMO protease, with essential functions in
      Cajal body biology.

PMID- 22878417
TI  - Highly emissive PEG-encapsulated conjugated polymer nanoparticles.
AB  - A novel bioimaging probe based on a conjugated polymer, poly(9,9-dihexylfluorene
      alt-2,1,3-benzoxadiazole) (PFBD), is demonstrated. Transfer of the hydrophobic
      polymer into water using a short chain poly(ethylene glycol) (PEG) resulted in
      conjugated polymer nanoparticles (PEG-PFBD) with a fluorescence quantum yield of
      46%. The PEG-PFBD nanoparticles possessed several desirable structural and
      photophysical properties, such as colloidal stability in a broad range of pH
      values, sub-20 nm particle size, the presence of surface chemical functionality,
      as well as desirable excitation and emission spectra, for bioimaging
      applications. PEG-PFBD nanoparticles were conjugated with cyclic RGDfK targeting
      peptide for labeling of membrane alpha(V)beta(3) integrin receptors on live HT-29
      adenocarcinoma cells. Single nanoparticle microscopy revealed that the PEG-capped
      PFBD nanoparticles exhibit at least ten times higher emitted photon counts than
      single quantum dots (QD655) of comparable size. In addition, Fluorescence
      Lifetime Imaging Microscopy (FLIM) of single PEG-PFBD nanoparticles revealed that
      the nanoparticles display a clearly resolvable single nanoparticle fluorescence
      lifetime.

PMID- 22878416
TI  - R-loops cause replication impairment and genome instability during meiosis.
AB  - R-loops are harmful structures with a negative impact on transcription and
      recombination during mitosis, but no information exists for meiosis. We used
      Saccharomyces cerevisiae and Caenorhabditis elegans THO mutants as a tool to
      determine the consequences of R-loops in meiosis. We found that both S.
      cerevisiae and C. elegans THO mutants show defective meiosis and an impairment of
      premeiotic replication as well as DNA-damage accumulation. Importantly, RNase H
      partially suppressed the replication impairment and the DNA-damage accumulation.
      We conclude that R-loops can form during meiosis causing replication impairment
      with deleterious results.

PMID- 22878418
TI  - Predicting estimates of oxygen transmissibility for scleral lenses.
AB  - BACKGROUND/PURPOSE: Although scleral contact lenses are prescribed with
      increasing frequency, little is known about their long-term effects on ocular
      physiology. The main goal of this paper is to predict values of oxygen
      transmissibility of scleral lens systems by applying the concept of resistors in
      series to parameters characteristic of current scleral lenses. A second aim is to
      find the maximal lens and post-lens tear layer thickness combinations above which
      hypoxia-induced corneal swelling would be found. METHODS: Theoretical
      calculations were used to predict the oxygen transmissibility of scleral lens
      systems, considering several material permeabilities (Dks 100-170), varying lens
      thicknesses (250-500 MUm), the known tear permeability (Dk of 80) and expected
      post-lens tear layer thicknesses (100-400 MUm). The Holden-Mertz Dk/t criteria of
      24 Fatt units for the central cornea and the Harvitt-Bonanno criteria of 35 Fatt
      units for the limbal area were used as reference points. RESULTS: Our
      calculations of oxygen transmissibility, with varying tear layer and lens
      thicknesses, ranged from 10 to 36.7 at the scleral lens centers and from 17.4 to
      62.6 at the peripheries. Our calculations of maximum central lens thicknesses
      show a practical range of 250-495 MUm, in conjunction with a post-lens tear layer
      thickness of 100-250 MUm. CONCLUSION: Our computations show that most modern
      scleral lenses, with recommended fitting techniques, should lead to some level of
      hypoxia-induced corneal swelling. Recommendations are made to minimize hypoxia
      induced corneal swelling: highest Dk available (>150) lens with a maximal central
      thickness of 250 MUm and fitted with a clearance that does not exceed 200 MUm.

PMID- 22878419
TI  - Factors affecting timing of antiretroviral treatment initiation based on
      monitoring CD4 counts.
AB  - OBJECTIVE: To evaluate factors affecting antiretroviral therapy (ART) start time
      when triggered by a CD4 count <350 cells/MUL while monitoring counts over time.
      Measurement frequency, requirement for confirmatory counts, and precision and
      accuracy of CD4 enumeration technology were considered. METHODS: Using a model of
      CD4 count trajectories among seroconverters in the Multicenter AIDS Cohort Study,
      sequences of counts were simulated for a large hypothetical population monitored
      for 5 years from seroconversion. Time of first count <350 cells/MUL was defined
      as ART start time. The simulation was adapted to evaluate the effect of the above
      factors on these times. ART initiation was considered "very late" among patients
      whose underlying trajectory declined less than 200 cells/MUL during the period
      simulated if no previous observed count was <350 cells/MUL. RESULTS: For 12-, 6-,
      4-, and 3-monthly measurements, median start time was 48, 36, 32, and 30 months
      after seroconversion and proportion of patients starting ART very late was 11.5%,
      1.6%, 0.2%, and 0.1%. For 6-monthly measurements, requiring confirmation
      increased the median to 49 months and proportion to 8.9%. Changes in standard
      deviation of short-term variability in counts of 25% and measurement bias for a
      novel technology of +/-10% changed median time by +/-6 months with modest change
      in the proportion very late (range, 0.5%-3.2%). CONCLUSION: : 6-monthly
      measurements appear adequate in achieving low rates of very late ART whereas
      confirmation affects rates adversely. Studies comparing new versus standard
      measurement technologies should focus on ruling out modest bias, particularly
      proximal to important thresholds for treatment management.

PMID- 22878420
TI  - "Global networks, alliances and consortia" in global health education-the case
      for south-to-south partnerships.

PMID- 22878421
TI  - Association of HIV infection with incident diabetes mellitus: impact of using
      hemoglobin A1C as a criterion for diabetes.
AB  - BACKGROUND: Data regarding the association between HIV and diabetes mellitus (DM)
      are conflicting, with little known regarding the impact of including hemoglobin
      A1C (A1C) as a criterion for DM. METHODS: Pooled logistic regression was used to
      quantify the association between HIV and DM in 1501 HIV-infected and 550 HIV
      uninfected participants from the Women's Interagency HIV Study. Incident DM was
      defined using the following 3 criteria, definition I: fasting glucose (FG) >=126
      mg/dL, anti-DM medication or reporting DM diagnosis (with confirmation by FG
      >=126 mg/dL or anti-DM medication); definition II: confirmation with a second FG
      >=126 mg/dL, and definition III: addition of A1C >=6.5% confirmed by FG >=126
      mg/dL or anti-DM medication. RESULTS: DM incidence per 100 person-years was 2.44,
      1.55, and 1.70 for HIV-infected women; 1.89, 0.85, and 1.13 for HIV-uninfected
      women, using definition I, II, and III, respectively. After adjustment for
      traditional DM risk factors, HIV infection was associated with 1.23-, 1.90-, and
      1.38-fold higher risk of incident DM, respectively; the association reached
      statistical significance only when confirmation with a second FG >=126 mg/dL was
      required. Older age, obesity, and a family history of DM were each consistently
      and strongly associated with increased DM risk. CONCLUSIONS: HIV infection is
      consistently associated with greater risk of DM. Inclusion of an elevated A1C to
      define DM increases the accuracy of the diagnosis and only slightly attenuates
      the magnitude of the association otherwise observed between HIV and DM. By
      contrast, a DM diagnosis made without any confirmatory criteria for FG >=126
      mg/dL overestimates the incidence, while also underestimating the effects of HIV
      on DM risk, and should be avoided.

PMID- 22878422
TI  - Synergistic effects of HIV infection and older age on daily functioning.
AB  - OBJECTIVE: To determine whether HIV infection and aging act synergistically to
      disrupt everyday functioning. DESIGN: Cross-sectional factorial study of everyday
      functioning in the context of HIV serostatus and age (<=40 years vs. >=50 years).
      METHODS: One hundred three HIV+ and 87 HIV- participants were administered
      several measures of everyday functioning, including self-report indices of health
      related quality of life (HRQoL) and instrumental and basic activities of daily
      living (IADLs and BADLs), and objective measures of functioning, including
      employment and Karnofsky Performance Scale ratings. RESULTS: Significant
      interaction effects of HIV and aging were observed for IADL and BADL declines,
      and for Karnofsky Performance Scale ratings (Ps < 0.05), independent of
      potentially confounding factors. Follow-up contrasts revealed significantly worse
      functioning in the older HIV+ group for most functional outcome measures relative
      to the other study groups (Ps < 0.05). A significant interaction effect was also
      observed on the emotional functioning HRQoL subscale, and additive effects of
      both age and HIV were observed for the physical functioning and general health
      perceptions HRQoL subscales (Ps < 0.05). Significant predictors of poorer
      functioning in the older HIV+ group included current major depressive disorder
      for all outcomes, and comorbid medical conditions, lower estimated premorbid
      functioning, neurocognitive impairment, and nadir CD4 count for selected
      outcomes. CONCLUSION: Findings suggest that older age may exacerbate the adverse
      effects of HIV on daily functioning, which highlights the importance of
      evaluating and monitoring the functional status of older HIV-infected adults.
      Early detection of functional difficulties could facilitate delivery of
      compensatory strategies (eg, cognitive remediation) or assistive services.

PMID- 22878423
TI  - The activity of the integrase inhibitor dolutegravir against HIV-1 variants
      isolated from raltegravir-treated adults.
AB  - BACKGROUND: Dolutegravir (DTG, S/GSK1349572) is an integrase inhibitor with low
      nanomolar potency. Susceptibility to dolutegravir and raltegravir was determined
      for raltegravir-resistant clinical isolates. METHODS: Genotypic and phenotypic
      susceptibility to integrase inhibitors was examined using 39 clinical isolate
      samples obtained from 18 adults who had exhibited incomplete viral suppression on
      a raltegravir-based regimen. RESULTS: Of 39 samples evaluated, 30 had genotypic
      and phenotypic resistance to raltegravir. All samples lacking raltegravir
      resistance retained complete susceptibility to dolutegravir. Of the 30 samples
      with genotypic evidence of raltegravir resistance, the median level of phenotypic
      resistance to raltegravir was high (median fold change in inhibitory
      concentration at 50%, >81; range, 3.7 to >87), while the level of resistance to
      dolutegravir was close to that of wild-type variants (median fold change, 1.5;
      range, 0.9-19.0). Longitudinal samples from 5 subjects collected during long-term
      failure of raltegravir revealed time-dependent general decreases in phenotypic
      susceptibility to raltegravir, with minimal changes in phenotypic susceptibility
      to dolutegravir. The median fold change to dolutegravir for isolates containing
      changes at G140S + Q148H, G140S + Q148R, T97A + Y143R, and N155H (thus including
      raltegravir signature resistance codons) were 3.75, 13.3, 1.05, and 1.37,
      respectively. CONCLUSIONS: Dolutegravir retained in vitro activity against
      clinical isolates obtained from subjects who failed raltegravir-based therapy at
      near wild-type levels for variants containing the Y143 and N155 resistance
      mutations. Isolates with Q148 plus additional integrase mutations possessed a
      broader range of and more reduced susceptibility to dolutegravir.

PMID- 22878424
TI  - Genital Inflammation Predicts HIV-1 Shedding Independent of Plasma Viral Load and
      Systemic Inflammation.
AB  - In women, genital HIV-1 RNA levels predict the risk of HIV-1 transmission
      independent of plasma viral load. To better understand the factors that
      contribute to genital HIV-1 shedding, we evaluated the relationships between
      genital and plasma cytokine concentrations and HIV-1 RNA levels. Vaginal, but not
      plasma, levels of interferon gamma-induced protein 10 (IP-10) were significantly
      associated with vaginal viral load, independent of plasma viral load. Thus,
      efforts to decrease HIV-1 transmission must take into account the role of local
      inflammation, which is not necessarily reflected in plasma measurements.

PMID- 22878425
TI  - Genomic characterization and expression profiles upon bacterial infection of a
      novel cystatin B homologue from disk abalone (Haliotis discus discus).
AB  - Cystatins are a large family of cysteine proteinase inhibitors which are involved
      in diverse biological and pathological processes. In the present study, we
      identified a gene related to cystatin superfamily, AbCyt B, from disk abalone
      Haliotis discus discus by expressed sequence tag (EST) analysis and BAC library
      screening. The complete cDNA sequence of AbCyt B is comprised of 1967 nucleotides
      with a 306 bp open reading frame (ORF) encoding for 101 amino acids. The amino
      acid sequence consists of a single cystatin-like domain, which has a cysteine
      proteinase inhibitor signature, a conserved Gly in N-terminal region, QVVAG motif
      and a variant of PW motif. No signal peptide, disulfide bonds or carbohydrate
      side chains were identified. Analysis of deduced amino acid sequence revealed
      that AbCyt B shares up to 44.7% identity and 65.7% similarity with the cystatin B
      genes from other organisms. The genomic sequence of AbCyt B is approximately 8.4
      Kb, consisting of three exons and two introns. Phylogenetic tree analysis showed
      that AbCyt B was closely related to the cystatin B from pacific oyster
      (Crassostrea gigas) under the family 1.Functional analysis of recombinant AbCyt B
      protein exhibited inhibitory activity against the papain, with almost 84%
      inhibition at a concentration of 3.5 MUmol/L. In tissue expression analysis,
      AbCyt B transcripts were expressed abundantly in the hemocyte, gill, mantle, and
      digestive tract, while weakly in muscle, testis, and hepatopancreas. After the
      immune challenge with Vibrio parahemolyticus, the AbCyt B showed significant
      (P<0.05) up-regulation of relative mRNA expression in gill and hemocytes at 24
      and 6 h of post infection, respectively. These results collectively suggest that
      AbCyst B is a potent inhibitor of cysteine proteinases and is also potentially
      involved in immune responses against invading bacterial pathogens in abalone.

PMID- 22878426
TI  - Cortisol modulates the expression of cytokines and suppressors of cytokine
      signaling (SOCS) in rainbow trout hepatocytes.
AB  - Although liver is a key target for corticosteroid action, its role in immune
      function is largely unknown. We tested the hypothesis that stress levels of
      cortisol down regulate immune-relevant genes in rainbow trout (Oncorhynchus
      mykiss) liver. Hepatocytes were treated with lipopolysaccharide (LPS) for 24h
      either in the presence or absence of cortisol. LPS stimulated heat shock protein
      70 expression, enhanced glycolytic capacity, and reduced glucose output. LPS
      stimulated mRNA abundance of cytokines and serum amyloid protein A (SAA), while
      suppressors of cytokine signaling (SOCS)-3 was reduced. Cortisol increased mRNA
      abundances of IL-1beta, SOCS-1 and SOCS-2, while inhibiting either basal or LPS
      stimulated IL-8, TNF alpha2 and SAA. These cortisol-mediated effects were rescued
      by Mifepristone, a glucocorticoid receptor antagonist. Altogether, cortisol
      modulates the molecular immune response in trout hepatocytes. The upregulation of
      SOCS-1 and SOCS-2 by cortisol may be playing a key role in suppressing cytokine
      signaling and the associated inflammatory response.

PMID- 22878427
TI  - Estimating the speed of Drosophila locomotion using an automated behavior
      detection and analysis system.
AB  - A fundamental phenotypic trait in Drosophila melanogaster is the speed of
      movement. Its quantification in response to environmental and experimental
      factors is highly useful for behavioral and neurological studies. Quantifying
      this behavioral characteristic in freely moving flies is difficult, and many
      current systems are limited to evaluating the speed of movement of one fly at a
      time or rely on expensive, time-consuming methods. Here, we present a novel
      signal processing method of quantifying the speed of multiple flies using a
      system with automatic behavior detection and analysis that we previously
      developed to quantify general activity. By evaluating the shape of the signal
      wave from recordings of a live and simulated single fly, a metric for speed of
      movement was found. The feasibility of using this metric to estimate the speed of
      movement in a population of flies was then confirmed by evaluating recordings
      taken from populations of flies maintained at two different temperatures. The
      results were consistent with those reported in the literature. This method
      provides an automated way of measuring speed of locomotion in a fly population,
      which will further quantify fly behavioral responses to the environment.

PMID- 22878429
TI  - FabryScan: a screening tool for early detection of Fabry disease.
AB  - Fabry disease, an X-linked lipid storage disorder, is associated early morbidity
      and mortality. Since enzyme replacement therapy is available, accurate detection
      of unrecognized cases is important. Characteristic early symptoms are recurrent
      episodes of burning and lancinating pain in the distal extremities associated
      with small fiber neuropathy. The aim was to develop and validate an easy
      diagnostic questionnaire in combination with three simple bedside tests, the
      "FabryScan", for the detection of Fabry disease in patients with chronic
      extremity pain. Questions related to relevant clinical characteristics of Fabry
      disease (mainly related to pain) were compiled by Fabry specialists and pain
      experts. Furthermore, three bedside tests assessing sensory small and large fiber
      function were established. The provisional version was tested in a prospective
      multicenter trial of 138 patients with chronic extremity pain due to Fabry
      disease (n = 55), painful polyneuropathy (n = 40), and rheumatoid arthritis (n =
      43). Identification of the most discriminant combinations of items for Fabry
      disease and their calculation of sensitivity and specificity were based on
      multivariate analyses. We retained only 10 questions and three bedside tests for
      the final version of the FabryScan. A cut-off score of 12/33 (corresponding to
      the number of positive points) resulted in a high proportion of correctly
      identified patients (76 %) with a sensitivity of 88 % and a specificity of 87 %.
      The FabryScan is a combination of a brief and simple questionnaire with three
      simple bedside tests with good discriminative value for the identification of
      Fabry patients in patients with chronic extremity pain.

PMID- 22878428
TI  - Botulinum toxin therapy: its use for neurological disorders of the autonomic
      nervous system.
AB  - Botulinum toxin (BoNT) has gained widespread use for the treatment of overactive
      muscles, overactive exocrine glands and, most recently, non-muscular pain
      conditions. Autonomic conditions treated with BoNT include achalasia,
      gastroparesis, sphincter of Oddi spasms, and unspecific esophageal spasms in
      gastroenterology and prostate disorders in urology. BoNT's use for autonomic
      conditions related to neurology includes various forms of bladder dysfunction
      (detrusor sphincter dyssynergia, idiopathic detrusor overactivity, neurogenic
      detrusor overactivity, urinary retention and bladder pain syndrome), pelvic floor
      disorders (pelvic floor spasms and anal fissures), hyperhidrosis (axillary,
      palmar, and plantar hyperhidrosis, diffuse sweating, Frey's syndrome) and
      hypersalivation (hypersalivation in Parkinsonian syndromes, motor neuron disease,
      neuroleptic use, and cerebral palsy). Hyperhidrosis, hypersalivation, some forms
      of bladder dysfunction and pelvic floor disorders can easily be treated by
      neurologists. Most bladder dysfunctions require cooperation with urology
      departments.

PMID- 22878430
TI  - Genetic risk factors in Parkinson's disease: single gene effects and interactions
      of genotypes.

PMID- 22878431
TI  - Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with
      chenodeoxycholic acid.
AB  - Polyneuropathy has been reported in cerebrotendinous xanthomatosis (CTX),
      although its nature and possible association with certain genotypes and
      phenotypes are unclear. The effect of chronic administration of chenodeoxycholic
      acid (CDCA) on peripheral nerve conduction parameters is still debated. We report
      clinical, laboratory, and electrophysiological findings in 35 CTX patients.
      Twenty-six subjects (74.2 %) showed peripheral nerve abnormalities.
      Polyneuropathy was predominantly axonal (76.9 % of patients) and generally mild.
      No correlation was found between its presence and clinical or biochemical data.
      In polyneuropathic patients, CDCA treatment improved electrophysiological
      conduction parameters, irrespective of the duration of therapy. Improvement
      mainly concerned nerve conduction velocities, whereas most nerve amplitudes
      remained unchanged. This means that CDCA treatment did not influence the number
      of axons activated by maximum electrical stimulation but increased the conduction
      of the still-excitable fibers. Our findings may suggest that CDCA treatment
      promotes myelin synthesis in nerve fibers with residual unaffected axons. The
      effect of therapy may therefore depend largely on the extent of irreversible
      structural damage to axons.

PMID- 22878433
TI  - Slow magnetic relaxation in homoleptic trispyrazolylborate complexes of
      neodymium(III) and uranium(III).
AB  - Lanthanide- and actinide-based single-molecule magnets are rapidly gaining
      prominence due to the unique properties of f-orbitals, yet no direct comparison
      of slow magnetic relaxation of an isostructural and valence isoelectronic
      lanthanide and actinide complex exists. We present the dynamic magnetic
      properties of two f-element single-molecule magnets, NdTp(3) and UTp(3) (Tp(-) =
      trispyrazolylborate), demonstrating that, although neither complex displays the
      full anisotropy barrier predicted from its electronic structure, relaxation is
      slower in the uranium congener. Magnetic dilution studies performed with NdTp(3)
      reveal that, while intermolecular interactions partially account for the faster
      relaxation dynamics, they are not uniquely responsible.

PMID- 22878432
TI  - Sativex long-term use: an open-label trial in patients with spasticity due to
      multiple sclerosis.
AB  - Sativex is an endocannabinoid system modulator principally containing Delta(9)
      tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised
      controlled trial, Sativex had a clinically relevant effect on spasticity
      associated with multiple sclerosis (MS). Patients self-titrated oromucosal
      Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and
      120 mg CBD daily). The primary objective was to evaluate the safety and
      tolerability of long-term treatment by recording the incidence and severity of
      adverse events (AEs). Secondary outcomes were to determine evidence of developing
      tolerance and to assess the long-term dosing profile of Sativex. A validated 11
      point Numerical Rating Scale of spasticity severity was used to assess efficacy.
      A total of 146 patients elected to enter this open-label follow-up safety trial.
      Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and
      patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two
      (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9
      % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10
      %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious
      AEs occurred in five patients (3.4 %), with two psychiatric events reported by
      one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred
      following abrupt cessation of treatment. Baseline symptoms including spasticity
      did not deteriorate but were maintained to study completion in those patients who
      did not withdraw. No new safety concerns were identified with chronic Sativex
      treatment, and serious AEs were uncommon. There was no evidence of tolerance
      developing, and patients who remained in the study reported continued benefit.

PMID- 22878434
TI  - Exercise dose and mobility outcome in a comprehensive stroke unit: description
      and prediction from a prospective cohort study.
AB  - OBJECTIVE: To describe the dose of lower limb exercise completed during admission
      to a stroke unit, establish predictors of dose and explore the relationship
      between dose and walking outcomes. DESIGN: Inception cohort study. PARTICIPANTS:
      Two hundred consecutively-admitted people with stroke. METHODS: Repetitions of
      exercise completed throughout the admission were tallied. Possible predictors of
      exercise dose were recorded within 48 h of admission. Walking velocity was
      assessed at the beginning and end of the hospital stay. RESULTS: Data were
      available for 191 (96%) participants on discharge. The mean daily dose of lower
      limb exercise was 288 repetitions (standard deviation (SD) 242), the variability
      in dose was best explained by age and disability level. The mean improvement in
      walking velocity was 0.43 m/s (SD 0.46), 26% of variability in walking
      improvement was explained by exercise repetitions and 29% was explained by a
      multivariable model including significant contributions from exercise repetitions
      (p < 0.01) and age (p = 0.03). After controlling for other factors, for every 100
      daily repetitions of lower limb exercise there was an additional change in
      walking velocity of 0.08 m/s (95% CI 0.05 to 0.11, p < 0.01). CONCLUSION:
      Exercise dose in a stroke unit is variable and can be predicted by age and
      disability. Increased exercise dose is associated with improved mobility
      outcomes.

PMID- 22878435
TI  - Effects of an educational audiovisual videodisc on patients' pre-operative
      expectations with total knee arthroplasty: a prospective randomized comparative
      study.
AB  - PURPOSE: To investigate the effectiveness of an educational videodisc in
      modifying pre-operative patients' expectations with total knee arthroplasty (TKA)
      and to find a biophysical profile of subjects in whom this videodisc could be
      most effective. It was hypothesized that patients receiving standard information
      plus additional medical information through audiovisual videodiscs would modify
      their pre-operative expectations more than those only receiving the standard
      information through medical interviews. METHODS: Ninety-two patients (age, 50-90
      years) with knee osteoarthritis waiting for TKA were randomized into two groups.
      All patients received general verbal information about this procedure. Forty-two
      patients (study group) additionally viewed an educational videodisc related to
      the whole process of TKA, whereas 50 patients did not view it (control group).
      Patients completed baseline and post-videodisc questionnaires regarding their
      expected results after TKA. RESULTS: Expectations with TKA were not modified by
      the audiovisual videodisc, except for knee range of motion and use of stairs.
      There were no differences in change of expectations between groups depending on
      demographic, functional, health, emotional, and cognitive variables, except for
      body mass index. The overall pre-operative, pre-intervention expectations were
      not modified by the audiovisual videodisc. CONCLUSIONS: Based on these results,
      the use of this complementary tool may not be systematically recommended. In
      addition, it was not possible to identify a biophysical profile of patients in
      whom the intervention could be most effective.

PMID- 22878436
TI  - The deltoid ligament: an in-depth review of anatomy, function, and treatment
      strategies.
AB  - PURPOSE: A literature review of the deltoid ligament was conducted, examining the
      current literature on anatomy, function, and treatment strategies. In particular,
      anatomical inconsistencies within the literature were evaluated, and detailed
      anatomical dissections are presented. METHODS: A literature search was conducted
      on PubMed using keywords relevant to the deltoid ligament in the ankle and medial
      ankle instability. Primary research articles, as well as appropriate summary
      articles, were selected for review. RESULTS: While it is well defined that the
      deltoid is contiguous and divided into one superficial and one deep portion, the
      creation of the individual fibres may be artificial. Furthermore, while
      improvements in imaging techniques and arthroscopy have not led to a consensus on
      the anatomy of the ligament, they may help improve recognition of deltoid
      injuries. Once identified, the majority of deltoid injuries can be treated via
      conservative treatment. However, reparative and reconstructive treatment
      strategies can also be used for complex acute injuries or chronic medial ankle
      instability. CONCLUSION: Given the continuing evolution of the anatomical
      understanding of the ligament, the current treatment protocol for deltoid
      injuries requires further standardization, with an emphasis on proper diagnosis.

PMID- 22878437
TI  - Development of the femoral trochlear groove in rabbits with patellar malposition.
AB  - PURPOSE: The geometry of the trochlear groove is considered to be an important
      determinant in the pathogenesis of the patellofemoral joint disorders. However,
      the effect of patellar position during the development of the femoral trochlear
      groove is unclear. This animal study aimed to investigate the relationship
      between the position of the patella and development of the femoral trochlear
      groove in growing rabbits. METHODS: Thirty-two knees from 16 rabbits were
      included in this study and were divided into two groups. First group consisted of
      the left knees and was used as a control group with no surgical interventions.
      The second group involved the right knees on which patellar tendon Z-plasty
      lengthening was performed to cause patellar malposition (patella alta) before 1
      month of age. Computed tomographic (CT) evaluations of both knees were obtained
      when the animals were 1 month age before the surgical intervention and also at 6
      months after the surgical intervention. Angle and depth measurements were
      acquired from the proximal, middle, and distal reference points along the femoral
      trochlear groove. After the CT scan acquisition at 6 months following the
      surgical procedures, rabbits were killed and additional measurements of the
      trochlear groove angles were performed manually. RESULTS: The mean middle and
      distal trochlear groove angles for the experiment group with patella alta were
      significantly higher compared to that of control group (p < 0.017). The increase
      in mean trochlear depth for the animals in the control group was found to be
      significantly higher compared to experiment group at the distal zone (p < 0.017).
      CONCLUSION: Distal femoral groove with an inadequately positioned patella becomes
      more flattened and this may be a predisposing factor for patellar instability.
      LEVEL OF EVIDENCE: Controlled laboratory study, Level II.

PMID- 22878438
TI  - Variability in knee laxity in anterior cruciate ligament deficiency using a
      mechanized model.
AB  - PURPOSE: To establish normative values for the magnitude of anterior tibial
      translation (ATT) in the Lachman and pivot shift tests in the intact and anterior
      cruciate ligament (ACL)-deficient states, and to explore whether a correlation in
      ATT magnitude exists between the Lachman and pivot shift tests. METHODS: Twenty
      six fresh frozen cadaveric hip-to-toe specimens were used. Mechanized testing was
      performed to simulate both a Lachman and pivot shift test with the ACL intact.
      Tests were repeated after sectioning the ACL. ATT was recorded using a computer
      navigation system. Difference in ATT after sectioning was calculated for each
      specimen. RESULTS: For the Lachman, mean lateral compartment ATT in the intact
      knee was 5.3 mm (SD = 2.8 mm). After sectioning the ACL, translation increased to
      11.4 mm (SD = 3.9 mm; P < 0.05). For the mechanized pivot shift, mean lateral
      compartment ATT in the intact knee was -0.2 mm (SD = 2.6 mm). After sectioning
      the ACL, translation increased to 8.2 mm (SD = 3.1 mm; P < 0.05). No correlation
      in the magnitude of ATT was found between the intact and ACL-deficient knees for
      either the Lachman or pivot shift tests, or between both tests (Cronbach's alpha
      < 0.7). CONCLUSIONS: No correlation was found between the Lachman and pivot shift
      test in both the intact and ACL-deficient knee. This suggests that the Lachman
      cannot be used as a surrogate for the pivot shift as the magnitude of the Lachman
      did not predict the magnitude of the pivot shift.

PMID- 22878439
TI  - The rapid evolution of knee osteotomies.

PMID- 22878440
TI  - Acquired lateral upper lid entropion in a child treated with Botulinum toxin.

PMID- 22878441
TI  - Using the real-life vision test to assess the functional vision of age-related
      cataract patients.
AB  - PURPOSE: (1) To describe and validate a newly developed, timed performance-based
      measures of functional vision-the real-life vision test (RLVT). (2) To determine
      how RLVT relates to clinical measures and self-report assessment of visual
      function and the complex interactions among visual impairment, psychosocial
      status, and demographic factors. METHODS: A total of 64 patients with age-related
      cataract and 45 age-matched controls were evaluated by four types of
      measurements: (1) demographic, medical, cognitive, and depressive evaluation and
      the reaction time (RT) testing; (2) clinical measures (visual acuity, contrast
      sensitivity, stereopsis, and the color perception); (3) the 25-item National Eye
      Institute's Visual Functioning Questionnaire; and (4) the RLVT. Spearman's
      coefficients, partial correlation, and multiple regression analysis were
      conducted to determine the relationship among RLVT, clinical measures, and self
      report assessment of visual function while controlling for confounders. RESULTS:
      Control subjects performed RLVT significantly better than the cataract patients.
      RLVT correlated well with both clinical and self-report assessments of visual
      function. All subscales of RLVT remained highly associated with most of the
      clinical measures, even after adjusting for age, years of education, depression,
      cognitive status, and the RT. Distance, intermediate and near visual acuity, and
      binocular contrast sensitivity were significant predictors of the RLVT
      performances. CONCLUSIONS: Given the strong relationship among RLVT, clinical
      measures, and the self-report assessments, our results highlight the potential
      usefulness of RLVT for assessing the functional vision of cataract patients. RLVT
      may provide information not obtainable from clinical measures or surveys and
      therefore it is essential to be incorporated into future ophthalmological
      practice.

PMID- 22878442
TI  - Prospective comparison between conventional microbial work-up vs PCR in the
      diagnosis of fungal keratitis.
AB  - PURPOSE: The PCR was compared with routine microbial studies for the detection of
      fungal pathogens in clinically suspected fungal keratitis. METHODS: A prospective
      nonrandomized study was undertaken at a tertiary eye care centre to evaluate 30
      eyes of 30 patients with presumed fungal keratitis, both fresh and treated.
      Corneal scrapings were performed on each patient. The specimens were analysed by
      a semi-nested PCR assay using fungal-specific primers. PCR products were cloned
      and sequenced for identification, and compared with a conventional microbial work
      up (smear and culture). RESULTS: Of the 30 samples, the PCR showed positivity in
      93.3%, culture in 40%, and potassium hydroxide in 20%. Of the 28 PCR-positive
      cases, 12 were culture-positive and 16 were culture-negative. Two samples were
      both PCR and culture test negative. Culture-negative samples were PCR-positive in
      16 of 18 (88.9%) cases. The PCR did not yield any false-negative findings in a
      culture-positive specimen. Both common and uncommon aetiologic fungi have been
      identified by DNA sequencing analysis. CONCLUSION: The PCR was able to detect
      fungal DNA in a high proportion of culture-negative cases. Technical
      considerations of the PCR process include extraction of artifacts and
      amplification of non-pathogenic DNA. Nonetheless, our findings suggest that the
      PCR can be a useful adjunct to smear and culture in the rapid diagnosis of fungal
      keratitis, particularly in cases of failed detection from routine procedures.

PMID- 22878443
TI  - Modelling postoperative visual acuity with and without proliferative
      vitreoretinopathy associated with primary rhegmatogenous retinal detachment.
AB  - PURPOSE: To find models that will explain the variability in postoperative visual
      acuity (VA) (logarithmic: logMAR) associated with unilateral primary
      rhegmatogenous retinal detachment (RD). METHODS: This was a prospective clinical
      cohort study of 33 patients with proliferative vitreoretinopathy (PVR: PVR<C3)
      and 33 without PVR, all of whom were candidates for scleral buckling (SB)
      surgery. Central retinal artery (CRA) Doppler sonography parameters (peak
      systolic, end diastolic velocities and resistibility index) and intraocular
      pressure (IOP) were measured before SB. Immunoreactive endothelin-1 (IR-ET-1)
      levels in both plasma and subretinal fluid (SRF) were measured using a
      radioimmunoassay. Visual outcomes were analysed by stepwise multivariate linear
      regression. The preoperative parameters used in the analysis included RD
      duration, IOP, logMAR VA, CRA parameters, preoperative plasma levels and
      intraoperative levels of IR-ET-1 in the SRF. RESULTS: The models for 8-month
      postoperative logMAR VA demonstrated a predictive power higher than 85%. The
      values of the 8-month-postoperative logMAR VA were as follows: (a) in No PVR= 
      0.151+0.06 preoperative duration (days), with a predictive power of 85.3%; (b) in
      PVR= -1.071+0.06 SRF IR-ET-1 (pg/ml)+0.459 preoperative logMAR VA explaining
      89.9% of the variability in the postoperative logMAR VA. CONCLUSIONS: The
      duration of RD and the levels of IR-ET-1 in the SRF appear to be the best
      explanatory variables in the models for 8-month-postoperative logMAR VA
      variability in RD patients. RD surgery should be performed as soon as possible to
      best preserve VA.

PMID- 22878444
TI  - Vitreous levels of somatostatin in patients with chronic uveitic macular oedema.
AB  - PURPOSE: Intravitreal somatostatin (SST) levels are decreased in patients with
      diabetic macular oedema. This deficit may be involved in the pathogenesis of this
      condition. The aim of the present study was to determine SST concentration in the
      vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and
      quiescent intraocular inflammation. METHODS: Plasma and vitreous fluid samples
      were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42
      eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST
      concentration was measured by radioimmunoassay. STATISTICS: chi(2)-square test,
      Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and
      multivariant linear regression models. RESULTS: Plasma SST concentrations were
      similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22
      29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic
      patients (1.59+/-0.38 mg/ml vs 0.73+/-0.32 mg/ml, P<0.0001). Vitreous SST was
      markedly lower in uveitic patients, both in absolute terms and after adjusting
      for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73
      pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024),
      P<0.0001). No correlations were found between plasma and vitreous concentration
      of SST in either group (rho=0.191, P=0.57 and rho=0.49, P=0.66). There were no
      correlations between vitreous SST concentration and visual acuity or macular
      thickness in uveitic patients (rho=0.302, P=0.31 and rho=0.45, P=0.13).
      CONCLUSIONS: Intravitreous SST is decreased in patients with CUMO and quiescent
      intraocular inflammation. The deficit of SST may have a role in the pathogenesis
      of this condition.

PMID- 22878445
TI  - Snailtrack corneal changes following subconjunctival injection of 5-fluorouracil.

PMID- 22878446
TI  - Accuracy and reliability of IOL master and A-scan immersion biometry in silicone
      oil-filled eyes.
AB  - PURPOSE: To compare the accuracy and reliability of intraocular lens (IOL) master
      and A-scan immersion biometry in silicone oil (SO)-filled eyes. METHODS: A
      prospective, consecutive, nonrandomized study was performed in 34 SO-filled eyes
      of 34 patients, who underwent a pars plana vitrectomy, with SO removal and
      cataract surgery, as well as IOL implantation. Both IOL master and immersion A
      scan were performed to measure the axial length (AXL) before SO removal. Three
      months after removal of the SO, AXL measurements using IOL master and refraction
      was performed. Accuracy of the two techniques was determined by a mean
      postoperative AXL using an IOL master and reliability was determined by mean
      actual postoperative refractive error. RESULTS: Preoperative mean AXL was 23.91+/
      0.24 mm (range 21.33-28.61 mm) and 23.71+/-0.59 mm (range 19.27-36.18 mm) by IOL
      master and A-scan immersion, respectively. Postoperative mean AXL by IOL master
      was 23.90+/-0.23 mm (range 21.58-27.94 mm), which showed a statistically
      significant difference from the preoperative mean AXL by A-scan immersion
      (P=0.005). The AXL measurement by IOL master also was more accurate than A-scan
      immersion by Pearson's correlation (0.966 vs 0.410). For reliability of the two
      techniques, the predictive postoperative refractive error in A-scan immersion
      (mean 1.79+/-1.04 D, range -14.62 to 16.41 D) was greater than that in IOL master
      (mean 0.60+/-0.23 D, range -2.74 to 2.33 D), with a statistically significant
      difference (P=0.049). CONCLUSION: IOL master had more accuracy and less deviation
      in predictive postoperative refractive error than A-scan immersion in SO-filled
      eyes.

PMID- 22878447
TI  - A sting in the tale: cross reaction hypersensitivity to hyaluronidase.

PMID- 22878448
TI  - Mutations in the CYP1B1 gene may contribute to juvenile-onset open-angle
      glaucoma.
AB  - PURPOSE: Glaucoma is one of the leading causes of blindness in the world.
      Juvenile-onset open-angle is a subtype of glaucoma. In this context, we
      investigate the possible mutations in the promoter and coding regions of the
      CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG).
      METHODS: The CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese
      probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted
      from peripheral blood leukocytes and then subjected to PCR. The amplified
      products were screened for base mutations by autosequence. Next, data from the
      two groups were compared using the chi(2) test. Additionally, three-dimensional
      (3D) modelling of the human wild-type and p.R390H mutation was performed using
      SWISS-MODEL, an automated homology modelling program. Finally, the figure was
      prepared for the modelled structures by using the Accelrys ViewerLite 5.0
      program. RESULTS: Analysis results indicated two CYP1B1 mutations and five
      polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92%
      (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a
      mutation in the 5'-untranslated region (c.1-313A>C; 1/3). Moreover, computer
      assisted modelling revealed that this p.R390H mutation affects the intra
      molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428,
      thus altering significantly the efficiency of the haem-binding and proper folding
      of the molecule. CONCLUSIONS: As a result, the p.Arg390His mutation might affect
      the protein structure and, ultimately, the normal function of CYP1B1. Therefore,
      we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk
      factor for the development of JOAG.

PMID- 22878450
TI  - A case of post-vaccination optic neuritis: coincidence or causative?

PMID- 22878449
TI  - Combining corneal hysteresis with central corneal thickness and intraocular
      pressure for glaucoma risk assessment.
AB  - PURPOSE: To determine whether adjusting corneal hysteresis (CH) values for
      central corneal thickness (CCT) and intraocular pressure (IOP) improves its
      capability to differentiate primary open-angle glaucoma (POAG) from ocular
      hypertension (OH). METHODS: This prospective, observational, cross-sectional
      study included 169 eyes of 169 subjects with a diagnosis of POAG (n=81) or OH
      (n=88). We utilized the Ocular Response Analyzer (ORA), Pascal Dynamic Contour
      Tonometer (DCT), Goldmann applanation tonometer (GAT), and ORA ultrasound
      pachymeter to obtain CH, IOP, and CCT values. Correlational, regression, and t
      test analyses were conducted before and after the sample was divided into low,
      intermediate, and thick CCT subgroups. RESULTS: In the full sample, CH and CCT
      were moderately correlated (r=0.44, P<0.001). Although both were related to
      diagnosis in univariate regression analysis, only CH was independently related to
      glaucoma diagnosis in multivariate analysis. After the sample was divided into
      CCT tertiles, CH was significantly lower in POAG vs OH eyes within all three CCT
      subgroups, and CH was the only multivariate variable that differentiated POAG
      from OH in each CCT subgroup. Moreover, the relationship between CH and diagnosis
      was more robust within the CCT subgroups compared with the full sample,
      suggesting that integrating CCT into CH interpretation is beneficial. Adjusting
      CH for IOP did not aid diagnostic precision in this study. CONCLUSION: Our
      findings suggest that combining CH and CCT for glaucoma risk assessment improves
      diagnostic capability compared to using either factor alone. Conversely,
      adjusting CH for IOP provided no clear clinical benefit in this study.

PMID- 22878451
TI  - Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the
      management of neovascular age-related macular degeneration in patients with
      persistent/recurrent macular fluid <30 days following treatment with intravitreal
      anti-VEGF therapy (the LAST Study).
AB  - PURPOSE: To determine the efficacy of intravitreal ranibizumab 2.0 mg in patients
      with recalcitrant neovascular age-related macular degeneration (AMD). METHODS:
      This single-masked, randomized, prospective, pilot study enrolled patients with
      subfoveal neovascular AMD. All study eyes had persistent subretinal (SRF) or
      intraretinal fluid (IRF) on spectral-domain optical coherence tomography (SD-OCT)
      <30 days following at least 6 monthly intravitreal injections of ranibizumab or
      bevacizumab. Patients were randomized 2 : 1 to receive either ranibizumab 2.0 or
      0.5 mg. Following three-loading treatments 4-weeks apart, both groups were
      treated using a 'treat and extend' regimen guided by eye-tracked SD-OCT through
      month 12. The primary end point was the mean change in best-corrected visual
      acuity (BCVA) at month 6. RESULTS: Nine eyes of 9 patients (mean age +/- SD, 82.0
      +/- 5.8 years) were enrolled. Seven eyes received ranibizumab 2.0 mg and two eyes
      received 0.5 mg. Owing to the small number of patients enrolled, no statistical
      comparison could be made between the two dosages. At month 6, the mean
      improvement in BCVA was +6.1 +/- 3.7 (W=0, P<0.001) ETDRS letters and +2.0 ETDRS
      letters in the 2.0 and 0.5 mg groups, respectively. In the 2.0 mg group, there
      was a statistically significant decline in central foveal thickness, SRF and
      maximum pigment epithelial detachment height at 6 months compared with baseline.
      No adverse events were reported in either group. CONCLUSION: Ranibizumab 2.0 mg
      has the potential to maintain or improve BCVA in some patients with persistent or
      recurrent SRF or IRF secondary to neovascular AMD despite prior monthly
      intravitreal anti-vascular endothelial growth factor therapy with the standard
      dose.

PMID- 22878452
TI  - Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium
      hyaluronate monotherapy in patients with dry eye syndrome: a prospective,
      randomized, multicenter study.
AB  - PURPOSE: To assess the additive effect of diquafosol tetrasodium on sodium
      hyaluronate monotherapy in patients with dry eye syndrome. METHODS: This study
      evaluated 64 eyes of 32 patients (age: 62.6+/-12.8 years (mean+/-SD)) in whom
      treatment with 0.1% sodium hyaluronate was insufficiently responsive. The eyes
      were randomly assigned to one of the two regimens in each patient: topical
      administration of sodium hyaluronate and diquafosol tetrasodium in one eye, and
      that of sodium hyaluronate in the other. Before treatment, and 2 and 4 weeks
      after treatment, we determined tear volume, tear film break-up time (BUT),
      fluorescein and rose bengal vital staining scores, subjective symptoms, and
      adverse events. RESULTS: We found a significant improvement in BUT (P=0.049,
      Dunnett test), fluorescein and rose bengal staining scores (P=0.02), and in
      subjective symptoms (P=0.004 for dry eye sensation, P=0.02 for pain, and P=0.02
      for foreign body sensation) 4 weeks after treatment in the diquafosol eyes. On
      the other hand, we found no significant change in these parameters after
      treatment in the control eyes. CONCLUSIONS: In dry eyes, where sodium hyaluronate
      monotherapy was insufficient, diquafosol tetrasodium was effective in improving
      objective and subjective symptoms, suggesting its viability as an option for the
      additive treatment of such eyes.

PMID- 22878453
TI  - Letter to the editor of Acta Neurochirurgica: intracranial venous drainage of a
      lumbar spinal dural arteriovenous fistula.

PMID- 22878454
TI  - Arachnoid cyst associated to spontaneous CSF fistula and massive pneumocephalus.

PMID- 22878455
TI  - Selection of resistance at lethal and non-lethal antibiotic concentrations.
AB  - Much of what we currently know about the genetics and evolution of antibiotic
      resistance is based on selections with lethal drug concentrations that allow the
      detection of rare mutants with strong phenotypes. These data may be misleading
      with regard to the evolution of antibiotic resistance in natural environments,
      because bacteria are frequently exposed to concentration gradients of
      antibiotics. A significant part of antibiotic-resistance evolution may occur when
      bacteria are exposed to non-lethal concentrations of drug. High-resolution
      competition assays show that resistance mutations are rapidly enriched, and
      selected de novo, at very low antibiotic concentrations. Genomic analysis is
      providing a better understanding of how frequent and small-effect mutations
      selected at very low antibiotic concentrations contribute to the step-wise
      development of antibiotic resistance.

PMID- 22878456
TI  - Acquisition of embryogenic competency does not require cell division in carrot
      somatic cell.
AB  - Totipotency is the ability of a cell to regenerate the entire organism, even
      after previous differentiation as a specific cell. When totipotency is coupled
      with active cell division, it was presumed that cell division is essential for
      this expression. Here, using the stress-induction system of somatic embryos in
      carrots, we show that cell division is not essential for the expression of
      totipotency in somatic/embryonic conversion. Morphological and histochemical
      analyses showed that the cell did not divide during embryo induction. Inhibitors
      of cell division did not affect the rate of somatic embryo formation. Our results
      indicate that the newly acquired trait of differentiation appears without cell
      division, but does not arise with cell division as a newborn cell.

PMID- 22878457
TI  - Isolated central nervous system relapse presenting as myeloid sarcoma of acute
      myeloid leukemia after allogeneic peripheral blood stem cell transplantation.

PMID- 22878458
TI  - Left and right ventricular function and volume assessment in young thalassemia
      major patients with no related myocardial iron overload.
AB  - Thalassemia major (TM) patients have altered ventricular volumes and ejection
      fraction compared to normals, although evidence for these findings stem from
      restricted patient groups and has never been reproduced. We sought to evaluate
      cardiac parameters by cardiovascular magnetic resonance (CMR) in a group of young
      TM patients not covered by previous studies that are more representative of the
      TM population in many countries. Seventy patients including 40 TM with normal
      myocardial iron concentrations, and 30 age- and gender-matched normal (NL)
      volunteers underwent a CMR study for assessment of left and right ventricle
      volumes and function using a 1.5-T scanner. Left and right ventricle ejection
      fraction, indexed systolic and diastolic volumes, and indexed mass were compared
      between the two groups. Mean age of TM patients was 18.2 +/- 7.1 versus 17.5 +/-
      8.5 years in NL with no significant differences (P = 0.73). There was no
      difference in left ventricular (LV) ejection fraction between the groups (TM 64.9
      +/- 5.7 %, NL 64.9 +/- 5.2 %; P = 0.97). LV normalized end-diastolic and end
      systolic volumes were significantly higher in patients with TM compared to NL
      volunteers (76.8 +/- 19.4 versus 66.6 +/- 11.7 mL/m2, P = 0.008, and 27.0 +/- 8.8
      versus 23.6 +/- 5.0 mL/m2, P = 0.045). LV indexed mass was also higher in TM
      patients compared to NL (51.2 +/- 11.9 versus 42.0 +/- 8.5 g/m2, P < 0.001). No
      significant differences were observed in right ventricular parameters. In
      conclusion, younger patients with TM do not present different left or right
      ventricular function values compared to normal controls despite having increased
      left ventricular volumes and mass.

PMID- 22878459
TI  - Images in anesthesiology:  vertebral osteomyelitis.

PMID- 22878460
TI  - Nucleation products of ligated nanoclusters unaffected by temperature and
      reducing agent.
AB  - Atomically uniform nucleation products of ligated metal nanoclusters are observed
      irrespective of reduction conditions for metal-bidentate ligand systems.
      Monodentate ligands are not reported to wield similar control, indicating steric
      contributions of complexing ligands may be as important as their electronic
      structure for synthesizing small nanoclusters.

PMID- 22878461
TI  - Changes in marital satisfaction across the transition to parenthood: the role of
      adult attachment orientations.
AB  - This longitudinal study investigated marital satisfaction trajectories across the
      first 2 years of parenthood. Data were collected from new parents (couples) 6
      weeks before the birth of their first child, and then at 6, 12, 18, and 24 months
      postpartum. Growth curve models revealed two key findings. First, for highly
      anxious individuals, satisfaction was lower or declined when they perceived their
      partners as less supportive and as behaving more negatively toward them. Second,
      for highly avoidant individuals, satisfaction was lower or declined when they
      perceived more work-family conflict and greater demands from their families. The
      findings suggest that attachment insecurities predict dissatisfaction in new
      parents primarily when stressors block the pursuit of important attachment goals.

PMID- 22878462
TI  - How much information? East Asian and North American cultural products and
      information search performance.
AB  - Literature in cultural psychology suggests that compared with North Americans,
      East Asians prefer context-rich cultural products (e.g., paintings and
      photographs). The present article further examines the preferred amount of
      information in cultural products produced by East Asians and North Americans
      (Study 1: Society for Personality and Social Psychology conference posters; Study
      2: government and university portal pages). The authors found that East Asians
      produced more information-rich products than did North Americans. Study 3 further
      examined people's information search speed when identifying target objects on
      mock webpages containing large amounts of information. The results indicated that
      East Asians were faster than North Americans in dealing with information on mock
      webpages with large amounts of information. Finally, the authors found that there
      were cultural differences as well as similarities in functional and aesthetic
      preferences regarding styles of information presentation. The interplay between
      cultural products and skills for accommodating to the cultural products is
      discussed.

PMID- 22878463
TI  - Detection of coronary artery disease using automated quantitation of myocardial
      perfusion on single-photon emission computed tomography images from patients with
      angina pectoris without prior myocardial infarction.
AB  - BACKGROUND: Whether or not automated scores obtained from myocardial single
      photon emission computed tomography (SPECT) imaging using software correlate with
      the visual interpretations by experts remains obscure. METHODS AND RESULTS:
      Eighty-seven consecutive patients with known or suspected angina pectoris
      underwent (201)thallium stress/rest SPECT followed by coronary angiography and
      the summed difference scores (SDS) were calculated using Heart Score View
      software. The SDS was substantially associated with coronary stenosis and
      accurately detected culprit lesions, because the diagnostic accuracy was
      comparable to that of expert visual evaluation. CONCLUSIONS: Automated scores
      obtained from myocardial SPECT can help detect coronary artery disease.  

PMID- 22878464
TI  - Elevated D-dimer is independently associated with endothelial dysfunction: a
      cross-sectional study in HIV-infected adults on antiretroviral therapy.
AB  - BACKGROUND: D-Dimer elevations have been associated with a striking increase in
      mortality in HIV-infected patients. However, D-Dimer has not been directly linked
      to endothelial dysfunction in HIV. METHODS: In this cross-sectional study, we
      used flow-mediated dilation (FMD) of the brachial artery to measure endothelial
      function and several biomarkers to measure systemic inflammation and coagulation
      activation in HIV-infected adults on stable antiretroviral therapy with HIV-1 RNA
      levels <400 copies/ml. Multivariable linear regression was used to model FMD by
      these markers, traditional cardiovascular risk factors and HIV-related
      characteristics. RESULTS: Analysis included 98 subjects (88% male, median age
      47.5 years, CD4(+) T-cells 578.5 cells/mm(3)); all on ART (52% on protease
      inhibitors). The only factors independently associated with FMD were D-Dimer and
      body mass index. CONCLUSIONS: We show for the first time an independent
      association between D-Dimer and endothelial dysfunction in virologically
      suppressed, HIV-infected adults on stable antiretroviral therapy, potentially
      explaining the link between D-Dimer and mortality in HIV.

PMID- 22878465
TI  - Microparticles: Modulators and biomarkers of liver disease.

PMID- 22878466
TI  - Hepatitis C infection, antiviral treatment and mental health: a European expert
      consensus statement.
AB  - Mental health problems frequently occur in chronic infection with the hepatitis C
      virus (HCV) and during antiviral treatment with pegylated interferon-alpha
      (PegIFNalpha) and ribavirin. Depression is one of the most important
      complications during antiviral treatment of chronic hepatitis C infection.
      However, an increased prevalence of depression, fatigue, and cognitive
      disturbances has also been reported in untreated HCV-positive patients. Patients
      with psychiatric disorders or drug addiction also have an increased risk of HCV
      infection. Furthermore, because of possible drug-drug interactions, new
      antivirals administered together with PegIFNalpha and ribavirin may complicate
      psychiatric side effect management, even if no specific psychiatric adverse
      events are known so far for these new drugs. The European liver patient's
      organization (ELPA) organised a European expert conference to review the
      literature and develop expert recommendations for the management of mental health
      problems in HCV infected patients. This paper results from the output of the 2011
      EASL meeting and subsequent dialogue with patient groups and relevant experts in
      Europe. It summarises the current knowledge of HCV infection and the brain;
      prevalence, course, and neurobiology of IFN-alpha associated psychiatric side
      effects; possible risk factors for IFN-alpha associated depression and suicide
      attempts; psychiatric management of HCV infected patients before and during
      antiviral treatment; prevention of IFN- alpha associated psychiatric side
      effects; and psychiatric aspects of the new antivirals. The summarised current
      knowledge about mental health changes before and during antiviral treatment
      should improve interdisciplinary management of HCV infected patients.

PMID- 22878467
TI  - Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects
      hepatic VLDL secretion in humans and in vitro.
AB  - BACKGROUND & AIMS: The robust association between non-alcoholic fatty liver
      disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been
      widely replicated. The aim of this study was to investigate the effect of the
      PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins
      (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777
      cells, which secrete VLDL-sized apoB-containing lipoproteins. METHODS: VLDL
      kinetics was analyzed after a bolus infusion of stable isotopes in 55
      overweight/obese men genotyped for the PNPLA3 I148M variant. Intracellular lipid
      content, apoB secretion and glycerolipid metabolism were studied in McA-RH 7777
      cells overexpressing the human 148I wild type or 148M mutant PNPLA3 protein.
      RESULTS: In humans, carriers of the PNPLA3 148M allele had increased liver fat
      compared to 148I homozygotes, and kinetic analysis showed a relatively lower
      secretion of the large, triglyceride-rich VLDL (VLDL(1)) in 148M carriers vs.
      148I homozygotes for the same amount of liver fat. McA-RH 7777 cells
      overexpressing the 148M mutant protein showed a higher intracellular triglyceride
      content with a lower apoB secretion and fatty acid efflux, compared to cells
      overexpressing the 148I wild type protein. The responses with 148M matched those
      observed in cells expressing the empty vector, indicating that the mutation
      results in loss of function. CONCLUSIONS: We have shown that PNPLA3 affects the
      secretion of apoB-containing lipoproteins both in humans and in vitro and that
      the 148M protein is a loss-of-function mutation. We propose that PNPLA3 148M
      promotes intracellular lipid accumulation in the liver by reducing the lipidation
      of VLDL.

PMID- 22878468
TI  - HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for
      antibody therapy of liver fibrosis.
AB  - BACKGROUND & AIMS: Activated hepatic stellate cells (HSCs) located in the Disse's
      space play a crucial role in liver fibrosis. HAb18G/CD147, a tumor-related
      glycoprotein, is highly expressed in hepatocellular carcinoma cells and
      fibroblasts. Whether HAb18G/CD147 plays an important role in the hepatic
      fibrogenesis is unknown. METHODS: Immunohistochemistry for HAb18G/CD147 and alpha
      smooth muscle actin expression in diseased liver tissues was used for correlation
      analysis. The function of HAb18G/CD147 in fibrogenesis was evaluated with the
      human HSCs LX-2 cell line and carbon tetrachloride-induced mouse liver fibrosis
      model. The specific antibody HAb18 targeting HAb18G/CD147 was injected
      intravenously into the mouse to investigate whether HAb18G/CD147 could be a
      potential target for liver fibrosis treatment. RESULTS: HAb18G/CD147 is highly
      expressed on activated HSCs in the sinusoid. The positive rates of HAb18G/CD147
      expression in human HBV-related liver cirrhosis, liver biopsy with HBV and liver
      adjacent to hemangioma were 95.6% (65/68), 14.8% (8/54) and 6.4% (8/125),
      respectively. HAb18G/CD147 expression was significantly correlated with the Child
      Pugh grade (r=0.2848, p=0.0186) and with the expression of alpha-smooth muscle
      actin in HSCs (r=0.4434, p=0.0002) in liver cirrhosis. Transforming growth factor
      beta1 upregulated HAb18G/CD147 expression in LX-2 cells. Transfection of
      HAb18G/CD147 promoted the profibrogenic genes expression. In mouse liver fibrosis
      model, HAb18G/CD147 expression increased with the development of fibrogenesis and
      decreased during the liver fibrosis spontaneous recovery. The HAb18 targeting
      HAb18G/CD147 could attenuate liver fibrosis. CONCLUSIONS: These data suggest that
      HAb18G/CD147 plays a role in HSC activation and is a potential therapeutic target
      in fibrosis/cirrhosis.

PMID- 22878470
TI  - A novel player in inflammation and cancer: the deubiquitinase CYLD controls HCC
      development.

PMID- 22878469
TI  - HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats
      without major systemic effects.
AB  - BACKGROUND & AIMS: Rho-kinase activation mediates cell contraction and increases
      intrahepatic resistance and consequently portal pressure in liver cirrhosis.
      Systemic Rho-kinase inhibition decreases portal pressure in cirrhosis, but also
      arterial pressure. Thus, liver-specific Rho-kinase inhibition is needed. The
      delivery of Rho-kinase inhibitor to activated hepatic stellate cells reduces
      fibrosis. It might also relax these contractile cells and therewith decrease
      intrahepatic resistance. We tested this hypothesis by performing acute
      experiments in cirrhotic rats. METHODS: Cirrhosis models were CCl(4)-intoxication
      and bile duct ligation. Three hours after injection of the Rho-kinase inhibitor
      (Y26732) coupled with a carrier (mannose-6-phosphate modified human serum
      albumin), which targets activated hepatic stellate cells, hemodynamics were
      analyzed by the colored microsphere technique and direct pressure measurements.
      The delivery site and effect of Rho-kinase inhibitor were investigated by
      immunohistochemical stainings, as well as Western blot. Experiments with Rho
      kinase inhibitor coupled with unmodified human serum albumin served as untargeted
      control. RESULTS: In both models of cirrhosis, the carrier coupled Rho-kinase
      inhibitor lowered the portal pressure and decreased the hepatic-portal
      resistance. Immunohistochemical desmin-staining showed the carrier in hepatic
      stellate cells. The targeted therapy decreased the expression of the
      phosphorylated substrate of Rho-kinase (moesin) and abolished myosin light chains
      phosphorylation in fibrotic septae (collagen-staining). The targeted Rho-kinase
      inhibitor showed no major extrahepatic effects. By contrast, the untargeted Rho
      kinase inhibitor elicited severe systemic hypotension. CONCLUSIONS: Activated
      hepatic stellate cells are crucially involved in portal hypertension in
      cirrhosis. Targeting of Rho-kinase in hepatic stellate cells not only decreased
      fibrosis, as previously shown, but also lowers portal pressure acutely without
      major systemic effects as demonstrated in this study.

PMID- 22878471
TI  - Decreased retinal sensitivity and loss of retinal nerve fibers in multiple system
      atrophy.
AB  - BACKGROUND AND AIM: In a previous study, retinal nerve fiber layer thickness
      (RNFLT) loss was shown as part of the neurodegenerative process in multiple
      system atrophy (MSA). Here, we investigate in a larger cohort of MSA patients
      whether the RNFLT loss translates into respective visual field defects. METHODS:
      Spectral domain optical coherence tomography was performed in 20 MSA patients
      (parkinsonian subtype = 12, cerebellar subtype = 8) to quantify peripapillary
      RNFLT. Visual field (90 degrees ) was analyzed by automated static perimetry to
      investigate retinal structure/function relationship. Eight data sets did not meet
      stringent quality criteria, and only 12 data sets were further analyzed. RESULTS:
      Compared to healthy controls, MSA patients demonstrated a significant reduction
      of RNFLT in the nasal sectors (p ( nasal-superior ) = 0.02, p ( nasal ) = 0.03, p
      ( nasal-inferior ) < 0.01), while changes in temporal RNFLT measures (p (
      temporal-superior ) = 0.42, p ( temporal ) = 0.34, p ( temporal-inferior ) =
      0.25) were not statistically significant compared to healthy controls (ANOVA).
      MSA patients featured a significant global mean deviation (2.74 dB; p < 0.01)
      without predominant peripheral visual field defects. Statistical analysis of mean
      defect in the central (0-30 degrees ), peripheral (30-90 degrees ) or global (0
      90 degrees ) visual field revealed no significant correlation (r (2) (central) =
      0.11, r (2) (peripheral) = 0.04, r (2) (global) = 0.07) with nasal RNFLT in MSA
      patients. CONCLUSION: MSA patients feature significant reduction in nasal RNFLT
      and global mean deviation when compared to healthy controls, consistent with the
      multi-systemic nature of this neurodegenerative disorder. This finding provides
      first evidence for two independent deteriorations of the visual system in MSA.

PMID- 22878472
TI  - A case of self-insertion of a foreign object into the lacrimal sac.

PMID- 22878473
TI  - Bilateral type 3 Duane retraction syndrome with bilateral tilted disc syndrome.

PMID- 22878474
TI  - Acidic fruit intake in relation to incidence and progression of urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Acidic fruits are commonly cited in the lay press as
      potential bladder irritants that may promote urinary incontinence (UI), but no
      epidemiologic studies have examined this issue. We hypothesized that higher
      intake of acidic fruits might be related to greater risk of UI incidence and
      progression in women. METHODS: In one set of analyses, we included women without
      UI at study baseline in the Nurses' Health Studies (NHS), with 34,144 women aged
      54-79 in NHS I and 31,024 women aged 37-54 in NHS II. These cohorts were
      established among women living in the USA. Incident UI was ascertained over 4
      years of follow-up, and acidic fruit consumption was measured by food frequency
      questionnaire prior to UI onset. In a second set of analyses, we examined UI
      progression over 2 years of follow-up among 11,764 women in NHS I and 11,299
      women in NHS II with existing UI. Multivariable-adjusted relative risks were
      calculated for the associations of acidic fruit intake and UI incidence and
      progression. RESULTS: We found no relation between acidic fruit intake and risk
      of developing UI, including urgency, mixed, and stress UI. In addition, there was
      no association between consumption of acidic fruits and UI progression,
      regardless of UI type. CONCLUSIONS: No associations were detected between acidic
      fruit intake and UI in this large, prospective study of women. These data have
      implications for the development of evidence-based dietary guidelines around
      acidic fruits and UI, particularly because acidic fruits likely have many health
      benefits.

PMID- 22878475
TI  - Reduced incidence of breast cancer-related lymphedema following mastectomy and
      breast reconstruction versus mastectomy alone.
AB  - BACKGROUND: As breast cancer survivorship has increased, so has an awareness of
      the morbidities associated with its treatment. The incidence of breast cancer
      related lymphedema has been reported to be 8 to 30 percent in all breast cancer
      survivors. To determine whether breast cancer reconstruction has an impact on the
      incidence of breast cancer-related lymphedema, the authors compared its incidence
      in patients who underwent mastectomy with reconstruction versus mastectomy alone.
      METHODS: All patients who underwent mastectomy, with or without immediate breast
      reconstruction, between 2001 and 2006, were identified through a search of
      prospective institutional databases. To reduce variation caused by known
      predictive factors, the individuals were cross-matched for age, axillary
      intervention, and postoperative axillary irradiation. The incidence of lymphedema
      was based on the presence of arm edema that lasted more than 6 months and was
      documented clinically. RESULTS: Of the 574 cross-matched patients included in the
      study, 78 (6.8 percent) developed lymphedema (21 with reconstructed breasts and
      57 with unreconstructed breasts). Patients who did not undergo reconstruction
      were significantly more likely to develop breast cancer-related lymphedema (9.9
      percent versus 3.7 percent; p < 0.001). Postoperative axillary radiation therapy
      (p < 0.001), one or more positive lymph nodes (p = 0.010), and body mass index of
      25 or greater (p = 0.021) were also associated with an increased incidence of
      lymphedema. Reconstruction patients developed lymphedema significantly later than
      nonreconstruction patients (p < 0.001). CONCLUSION: Patients who undergo breast
      reconstruction have a lower incidence and a delay in onset of breast cancer
      related lymphedema compared with patients who undergo mastectomy alone. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 22878476
TI  - The staged face lift:  addressing the biomechanical limitations of the primary
      rhytidectomy.
AB  - BACKGROUND: Although early secondary face lift is a highly scrutinized procedure,
      it is beneficial for a select group of patients. Justification for performing the
      early secondary face lift or staged face lift is more apparent when considering
      the biomechanical limitations of the primary face lift. METHODS: All patients
      undergoing primary face-lift procedures performed by the senior author (T.A.M.)
      between 1998 and 2008 were followed for 2 years to determine which patients would
      benefit from an early secondary rhytidectomy. Early secondary face lifts were
      performed in the same sub-superficial musculoaponeurotic system plane as the
      primary procedure and entailed full undermining. RESULTS: Forty-seven of 742
      patients (6.3 percent) undergoing a primary face-lift procedure underwent an
      early secondary rhytidectomy. Identified limiting factors of the primary face
      lift included suture-tearing force, viscoelastic properties (tissue creep and
      stress relaxation), blood supply, and an attempt to avoid an overly pulled
      appearance. Indications for early secondary rhytidectomy included early symptoms
      of recurrence or residual age-related changes in patients with severe
      preoperative laxity or poor soft-tissue elasticity and mainly involved the
      perioral region. There were no significant complications and there was high
      patient satisfaction in all cases. CONCLUSION: With thorough understanding of the
      viscoelastic properties of facial tissues and proper consultation with patients,
      the early secondary face lift can be used as a safe and effective option with
      which to address the limitations of a primary face lift. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 22878477
TI  - The contribution of endogenous and exogenous factors to female alopecia:  a study
      of identical twins.
AB  - BACKGROUND: In this study, the authors investigated the potential contribution of
      environmental factors and testosterone levels on androgenic alopecia in women.
      METHODS: Ninety-eight identical female twins were recruited from 2009 to 2011.
      Subjects were asked to complete a comprehensive questionnaire, provide a sputum
      sample for testosterone analysis, and pose for standardized digital photography.
      Frontal, temporal, and vertex hair loss were assessed from the photographs using
      Adobe Photoshop. Hair loss measures were then correlated with survey responses
      and testosterone levels between twin pairs. Two independent, blinded observers
      also rated the photographs for hair thinning. RESULTS: Factors associated with
      increased frontal hair loss included multiple marriages (p = 0.043); longer sleep
      duration (p = 0.011); higher severity of stress (p = 0.034); positive smoking
      history (p = 0.021); higher income (p = 0.023); absence of hat use (p = 0.017);
      and history of diabetes mellitus (p = 0.023), polycystic ovarian syndrome (p =
      0.002), and hypertension (p = 0.001). Factors associated with increased temporal
      hair loss included divorce or separation (p = 0.034), multiple marriages (p =
      0.040), more children (p = 0.005), longer sleep duration (p = 0.006), and history
      of diabetes mellitus (p = 0.008) and hypertension (p = 0.027). Lack of sun
      protection (p = 0.020), consuming less caffeine (p = 0.040), history of skin
      disease (p = 0.048), and lack of exercise (p = 0.012) were associated with
      increased vertex hair loss. Higher testosterone levels were associated with
      increased temporal and vertex hair loss patterns (p < 0.039). Increased stress,
      increased smoking, having more children, and having a history of hypertension and
      cancer were all associated with increased hair thinning (p < 0.05). CONCLUSION:
      This study implicates several environmental risk factors in the pathophysiology
      of female alopecia.

PMID- 22878478
TI  - Achieving differential facial changes with Le Fort III distraction osteogenesis:
      the use of nasal passenger grafts, cerclage hinges, and segmental movements.
AB  - BACKGROUND: In traditional Le Fort III distraction, the transport segment is
      advanced en bloc without addressing differences in the relative retrusion of the
      facial structure. The authors describe three methods for correcting these
      asymmetries with differential facial advancement. METHODS: Eight patients (age
      range, 4 to 20 years) with asymmetric facial hypoplasia were treated by Le Fort
      III midface distraction using an external device. Two patients with nasal bone
      hypoplasia exceeding midface retrusion were treated with nasal passenger grafts
      at the time of osteotomy. Two patients with asymmetric rotational midface
      deformities underwent wire cerclage swing advancement of the affected side to
      achieve differential advancement. Four patients with central nasomaxillary
      retrusion exceeding zygomatic retrusion underwent segmental Le Fort III osteotomy
      with simultaneous zygoma repositioning and Le Fort II distraction. RESULTS:
      Differential midface advancement was achieved in all patients. Midface
      distraction and nasal passenger grafts resolved obstructive sleep apnea, improved
      globe protection, and improved fit of prescription glasses. After Le Fort III
      swing advancement, the centric relation and malar asymmetry were corrected with
      differential advances of 10 and 15 mm compared with the unaffected side. In the
      segmental osteotomy Le Fort III group, the central face was distracted
      independently of the zygoma repositioning, thus correcting the shortened retruded
      central midface without distorting the orbitomalar relationship and improving
      airway obstruction, anterior open bite, short nose, and proptosis. CONCLUSIONS:
      Midface distraction techniques have evolved to include the principles of
      segmentation, graft augmentation, and controlled rotation. The benefits of
      gradual distraction can be realized without compromising the aesthetic and
      functional result.

PMID- 22878479
TI  - A new technique for repair of flexor digitorum profundus tendon complete
      laceration in zone 1.

PMID- 22878480
TI  - Donor-site lymphatic function after microvascular lymph node transfer.
AB  - BACKGROUND: Lymphedema remains a challenging clinical problem that often lacks
      curative treatment options. Recent reports have shown that microvascular lymph
      node transfer from the groin area into axillas of lymphedematous patients may
      improve lymphatic drainage, but the effect on donor-site lymphatic flow has not
      been studied. These patients may be more prone to develop lymphedema at donor
      sites as well; therefore, the authors' aim was to evaluate postoperative donor
      site lymphatic function. METHODS: The authors performed lymphatic groin flap
      transfer to the axilla in 13 lymphedema patients. In 10 patients, the lymph node
      transfer was performed simultaneously with lower abdominal breast reconstruction.
      Postoperative lymphatic vessel function of the donor site was evaluated by
      lymphoscintigraphy and limb circumference measurements. For semiquantitative
      evaluation of lymphatic drainage, a numerical transport index was used. RESULTS:
      In six of 10 patients, postoperative lymphoscintigraphy revealed minor changes in
      lymphatic flow of the donor-site limbs. The transport index was considered
      slightly abnormal in two of 10 patients. None of the 13 patients had changes in
      lower limb circumferences during the 8- to 56-month follow-up. CONCLUSIONS: Lymph
      node transfer can be easily combined with lower abdominal breast reconstruction,
      and the popularity of this technique is increasing rapidly. Even though none of
      our patients had developed symptoms of postoperative lymphedema, the results of
      the first lymphoscintigrams show that it is important to reduce the surgical
      trauma to the lymphatic flap donor site. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 22878482
TI  - Nanotechnology in plastic surgery.
AB  - BACKGROUND: Nanotechnology has made inroads over time within surgery and
      medicine. Translational medical devices and therapies based on nanotechnology are
      being developed and put into practice. In plastic surgery, it is anticipated that
      this new technology may be instrumental in the future. Microelectromechanical
      systems are one form of nanotechnology that offers the ability to develop
      miniaturized implants for use in the treatment of numerous clinical conditions.
      The authors summarize their published preliminary findings regarding a
      microelectromechanical systems-based electrochemical stimulation method through
      modulation of ions around the nerve that is potentially implantable and
      clinically efficacious, and expand upon current and potential usages of
      nanotechnology in plastic surgery. METHODS: Sciatic nerves (n = 100) of 50
      American bullfrogs were placed on a microfabricated planar gold electrode array
      and stimulated electrically. Using Ca(2+)-selective membranes, ion concentrations
      were modulated around the nerve environment in situ. In addition, a comprehensive
      review of the literature was performed to identify all available data pertaining
      to the use of nanotechnology in medicine. RESULTS: A 40 percent reduction of the
      electrical threshold value was observed using the Ca(2+) ion-selective membrane.
      The uses of nanotechnology specifically applicable to plastic surgery are
      detailed. CONCLUSIONS: Nanotechnology may likely lead to advancements in the art
      and science of plastic surgery. Using microelectromechanical systems
      nanotechnology, the authors have demonstrated a novel means of modulating the
      activation of nerve impulses. These findings have potentially significant
      implications for the design of special nano-enhanced materials that can be used
      to promote healing, control infection, restore function, and aid nerve
      regeneration and rehabilitation.

PMID- 22878481
TI  - Quantitative histologic evidence of amifostine-induced cytoprotection in an
      irradiated murine model of mandibular distraction osteogenesis.
AB  - BACKGROUND: Head and neck cancer management requires adjuvant radiotherapy. The
      authors have previously demonstrated the damaging effect of a human equivalent
      dose of radiation on a murine mandibular model of distraction osteogenesis. Using
      quantitative histomorphometry, the authors' specific aim was to objectively
      measure amifostine radioprotection of the cellular integrity and tissue quality
      of an irradiated and distracted regenerate. METHODS: Sprague-Dawley rats were
      assigned randomly into two groups: radiotherapy/distraction osteogenesis and
      amifostine/radiotherapy/distraction osteogenesis, which received amifostine
      before radiotherapy. Both groups received a fractionated human equivalent dose of
      radiation prior to left mandibular osteotomy with fixator placement. Distraction
      to 5.1 mm was followed by a 28-day consolidation period. Quantitative
      histomorphometry was performed on left hemimandibles for osteocytes, empty
      lacunae, bone volume-to-tissue volume ratio, and osteoid volume-to-tissue volume
      ratio. RESULTS: Amifostine/radiotherapy/distraction osteogenesis exhibited bony
      bridging as opposed to radiotherapy/distraction osteogenesis fibrous unions.
      Quantitative histomorphometry analysis revealed statistically significant higher
      osteocyte count and bone volume-to-tissue volume ratio in amifostine-treated
      mandibles compared with irradiated mandibles. There was a corresponding decrease
      in empty lacunae and the ratio of osteoid volume-to-tissue volume between both
      groups. CONCLUSIONS: The authors have successfully established the significant
      osseous cytoprotective and histoprotective capacity of amifostine for distraction
      osteogenesis in the face of radiotherapy. The amifostine-sparing effect on bone
      cellularity correlated with increased bony unions and elimination of fibrous
      union. The authors posit that the demonstration of similar efficacy of amifostine
      in the clinic may allow the successful implementation of distraction osteogenesis
      as a viable reconstructive option for head and neck cancer in the future.

PMID- 22878483
TI  - Single-ion magnet behaviour in [U(Tp(Me2))2I].
AB  - [U(Tp(Me2))(2)I] exhibits at low temperatures single molecule magnet (SMM)
      behaviour comparable to its bipyridine derivative and related single ion U(III)
      complexes recently reported as SMMs. The trend of variation of the energy barrier
      for the magnetic relaxation in these compounds is well reproduced by quantum
      chemistry calculations.

PMID- 22878484
TI  - Effects of fluoride in bone repair: an evaluation of RANKL, OPG and TRAP
      expression.
AB  - The objective of this study was to evaluate comparatively the effect of fluoride
      in the expression of the receptor activator of nuclear factor kappa B ligand
      (RANKL), osteoprotegerin (OPG) and tartrate-resistant acid phosphatase (TRAP) in
      alveolar bone repair in rats. We used 3 groups of male Wistar rats (n = 5/group),
      which received drinking water containing different doses of F (NaF): 0, 5 and 50
      ppm, for 60 days before the incisors extraction. The upper incisors were
      extracted and the animals were killed 7, 14, 21 and 30 days after extraction. The
      hemi-maxillae were collected for microscopic examination (histomorphometric and
      immunostaining for RANKL, OPG and TRAP). Histomorphometric analysis confirmed an
      increase in the volume density of neoformed bone between 7 and 30 days for groups
      control, 5 and 50 ppm of F, with a concomitant decrease in the volume density of
      connective tissue and blood clot. Higher blood clot for groups 5 and 50 ppm of F
      at 30 days was observed. The RANKL and OPG expressions were not changed by
      chronic exposure to fluoride in the drinking water during the studied periods; on
      the other hand, TRAP expression was changed (at 7 days) by chronic exposure to
      fluoride (p < 0.05). It was concluded that F in high concentrations can slow the
      blood clot remission and bone repair, and alter the TRAP expression in the
      beginning of the bone tissue repair. However, a better understanding about this
      blood clot remission phenomenon is required.

PMID- 22878486
TI  - Limitations of habitats as biodiversity surrogates for conservation planning in
      estuaries.
AB  - Increasing pressures on global biodiversity and lack of data on the number and
      abundance of species have motivated conservation planners and researchers to use
      more readily available information as proxies or surrogates for biodiversity.
      "Habitat" is one of the most frequently used surrogates but its assumed value in
      marine conservation planning is not often tested. The present study developed and
      tested three alternative habitat classification schemes of increasing complexity
      for a large estuary in south-east Australia and tested their effectiveness in
      predicting spatial variation in macroinvertebrate biodiversity and selecting
      estuarine protected areas to represent species. The three habitat classification
      schemes were: (1) broad-scale habitats (e.g., mangroves and seagrass), (2)
      subdivision of each broad-scale habitat by a suite of environmental variables
      that varied significantly throughout the estuary, and (3) subdivision of each
      broad-scale habitat by the subset of environmental variables that best explained
      spatial variation in macroinvertebrate biodiversity. Macroinvertebrate
      assemblages differed significantly among the habitats in each classification
      scheme. For each classification scheme, habitat richness was significantly
      correlated with species richness, total density of macroinvertebrates, assemblage
      dissimilarity, and summed irreplaceability. However, in a reserve selection
      process designed to represent examples of each habitat, no habitat classification
      scheme represented species significantly better than a random selection of sites.
      Habitat classification schemes may represent variation in estuarine biodiversity;
      however, the results of this study suggest they are inefficient in designing
      representative networks of estuarine protected areas.

PMID- 22878487
TI  - Evaluation of applicability of the Sartorius Airport MD8 sampler for detection of
      Bacillus endospores in indoor air.
AB  - This study was designed to evaluate the measuring range and lowest limit of
      detection of Bacillus endospores in the ambient room air when the Sartorius MD8
      sampler, and two different culture methods for bacterial enumeration were used.
      Different concentrations of bioaerosol were generated inside the test chamber
      filled with either the high-efficiency particulate air (HEPA)-filtered air or
      with the ambient room air. The detection of endospores in the HEPA-filtered air
      was achievable: (1) when they were aerosolized at a concentration above 7.56 *
      10(3) CFU/m(3) and analyzed with spread plate method, and (2) when they were
      aerosolized at a concentration above 4.00 * 10(2) CFU/m(3) and analyzed with pour
      plate method. The detection of endospores in the ambient room air was possible:
      (1) when they were aerosolized at a concentration above 9.1 * 10(3) CFU/m(3) and
      analyzed with spread plate method, and (2) when they were aerosolized at a
      concentration above 5.6 * 10(2) CFU/m(3) and analyzed with pour plate method. The
      microorganisms present in the ambient room air interfere with precise
      quantification of Bacillus endospores when their concentration is relatively low.
      The results of this study may be helpful in critical assessment of the results
      obtained from monitoring the air for bacterial endospores.

PMID- 22878488
TI  - Necrotizing fasciitis:  a six-year experience.

PMID- 22878489
TI  - Observations on serial plasma citrulline concentrations in a patient with
      intestinal ischemia and full-thickness necrosis after severe thermal injury.

PMID- 22878490
TI  - Serum vancomycin levels resulting from continuous or intermittent infusion in
      critically ill burn patients with or without continuous renal replacement
      therapy.
AB  - We evaluated vancomycin levels as recent guidelines for therapeutic monitoring of
      vancomycin (not available at the time these data were collected) recommend trough
      levels of 15 to 20 MUg/mL; however, this may be more difficult to achieve in
      patients with accelerated vancomycin clearance, such as burn patients or
      recipients of continuous venovenous hemofiltration (CVVH) therapy. We
      retrospectively studied 2110 serum vancomycin levels of 171 patients admitted to
      the burn intensive care unit for more than 4 years and who received vancomycin by
      continuous infusion (CI) or intermittent infusion (II), with or without
      simultaneous CVVH. In-hospital mortality, 14- and 28-day mortality following
      vancomycin therapy were not different between dosing methods, although increased
      mortality was observed in the subgroup of patients receiving CI vancomycin
      empirically for clinical sepsis with negative blood cultures. More vancomycin was
      delivered to patients daily by CI than II, and therapeutic drug monitoring costs
      were similar. After controlling for differences in vancomycin dose by case
      matching with propensity scores, mean vancomycin levels were 20.0 +/- 3.8 MUg/mL
      for CI, vs 14.8 +/- 4.4 MUg/mL for II (P < .001). CI dosing resulted in similar
      levels with or without CVVH, whereas in II dosing, CVVH appeared to significantly
      decrease vancomycin levels. Although CI dosing was associated with higher
      vancomycin levels in general and fewer levels of <10 MUg/mL, significant
      nephrotoxicity or neutropenia was not observed. Fifty-seven patients (33.3%)
      developed bacteremia, and 106 Gram-positive bacteria were recovered, including 63
      Staphylococcus aureus. Recurrent bacteremia while receiving vancomycin was
      infrequent. The 90th percentile minimum inhibitory concentration (MIC90) for
      vancomycin of 36 available S. aureus isolates tested by broth microdilution was
      1.5 MUg/mL. CI produced more frequent therapeutic vancomycin levels and less
      frequent subtherapeutic levels compared to II. However, therapeutic vancomycin
      levels were achieved infrequently by either method of dosing. Given equivalent
      therapeutic drug monitoring costs and the lack of a clear clinical benefit, the
      role of CI dosing remains to be defined in spite of practical and theoretical
      advantages, particularly when administered in the setting of CVVH.

PMID- 22878491
TI  - Ketamine-propofol vs ketamine-dexmedetomidine combinations in pediatric patients
      undergoing burn dressing changes.
AB  - The aim of this study was to compare ketamine-propofol (KP) and ketamine
      dexmedetomidine (KD) combinations for deep sedation and analgesia during
      pediatric burn wound dressing changes. After obtaining approval from the
      University Ethics Committee, burn wound care or wound dressing changes were
      performed on 60 American Society of Anesthesiologists physical status I and II
      inpatients aged between 8 and 60 months with second-degree burns ranging from 5
      to 25% TBSA. After recording the demographic data, the heart rate, systolic
      arterial pressure, diastolic arterial pressure, peripheral oxygen saturation,
      respiratory rate, and Ramsey sedation scores were recorded for all patients
      before and during the procedure. Group KP (n = 30) received 1 mg kg-1 ketamine +
      1 mg kg-1 propofol and group KD (n = 30) received 1 mg kg-1 ketamine + 0.5 MUg kg
      1 dexmedetomidine for induction. Additional propofol (1 mg kg-1) for group KP and
      additional dexmedetomidine (0.5 MUg kg-1) for group KD were administered when
      required. No statistically significant differences in sedation scores and
      peripheral oxygen saturation and diastolic arterial pressure (P > .05) were found
      between the two groups. However, systolic blood pressure values in group KD
      showed a significant increase after induction (P < .05). The recovery time was
      longer in group KD than in group KP (P < .05). The respiratory rate was higher in
      group KD than in group KP beginning from the fifth minute of the procedure. A
      significant amount of respiratory depression and hypoxia was observed in group KP
      but not in KD (P < .05). Both the KP and KD combinations were effective for
      sedation and analgesia during dressing changes in the pediatric burn patients.
      The KD combination can be considered as an excellent alternative for pediatric
      wound dressing changes which does not result in respiratory depression.

PMID- 22878492
TI  - Tracking non-burn center care:  what you don't know may surprise you.
AB  - The American Burn Association publishes a list of defined criteria for patients
      who require admission or transfer to a burn center. This study examines the
      extent to which those criteria are observed within a regional burn network.
      Hospital discharge data for 2008 were obtained for all hospitals within the South
      Florida regional burn network. Patients with International Classification of
      Diseases, 9th revision discharge diagnoses for burns were reviewed, and their
      triage destination was compared with the burn triage referral criteria to
      determine whether patients were inappropriately triaged. Descriptive statistics
      were used to analyze the data. Four hundred ninety-eight burn admissions were
      documented to non-burn center center hospitals, 269 (54%) of which were deemed
      inappropriate by burn triage referral criteria. Burn center patients had greater
      length of stay when compared with non-burn center patients (14 vs 7 days), but a
      greater percentage were discharged home for self-care (88 vs 57%). Thirty-three
      percent of the inappropriate admissions were in a neighboring county, whereas 27%
      were in the same county where the burn center is located. Inappropriate burn
      patient triage may be occurring to more than half of the burn patients within our
      regional burn network despite better functional outcomes at the burn center. This
      may be because of a lack of knowledge regarding triage criteria, patient
      insurance status, or other factors. Further studies are necessary to fully
      characterize the problem and implement education or incentives to encourage
      appropriate burn patient triage.

PMID- 22878493
TI  - Friction burns in children:  does laser Doppler imaging have a role?
AB  - Laser Doppler imaging (LDI) has been increasingly used to predict pediatric burn
      wound outcome. A majority of these wounds are scald, contact, or flame burns. No
      study has specifically evaluated the use of LDI in pediatric friction burns. Our
      objective was to critically evaluate LDI assessment of pediatric friction burns
      to determine its predictive value with this mechanism of injury. We conducted a
      retrospective review of all LDI scans performed on pediatric friction burns
      during a 2-year period. We identified 36 patients with a mean age of 3.6 years
      (range, 19 months to 15 years). LDI accurately predicted burn wound outcome in 23
      (64%) cases. In 13 cases, LDI did not correctly predict burn wound outcome. Eight
      were expected to heal within 14 days, but six of those eight took an average of
      20.3 days to heal (range, 18-29 days), and the other two required skin grafting.
      Of the remaining five incorrect predictions, four were caused by an inability to
      correlate the flux scan with the clinical appearance of the burn, and one was
      thought to take more than 21 days to heal but healed within this period. Our data
      suggest that LDI appears to be a less reliable tool in predicting the outcome of
      friction burns when compared to other mechanisms of burn injury in children. This
      may reflect the physical differences in the mechanism of friction burns as
      opposed to other forms of thermal injury.

PMID- 22878494
TI  - A rationale for significant cost savings in patients suffering home oxygen burns:
      despite many comorbid conditions, only modest care is necessary.
AB  - Increasingly, patients are being evaluated for burns related to home oxygen use.
      Although the majority of burns are minor, referral to a burn unit regardless of
      depth or size is still common. The care of this population was reviewed to
      determine the feasibility and potential saving if such patients could be managed
      by nonburn-trained surgeons. Prospectively collected data on 5103 consecutive
      patients admitted to an urban tertiary burn center between April 1997 and
      September 2010 was reviewed. Data collected included age, TBSA burned,
      comorbidities, mode of admission, distance transported, mode of transport, number
      requiring surgery, length of stay, and outcome. Of 5103 admissions, 64 were for
      home oxygen burns. Patients had a mean age of 62.5 years and five comorbidities.
      They suffered a mean 4% TBSA burn, and all were mostly superficial, of partial
      thickness, and healed without surgery. Patients had a mean length of stay of 2
      days and required one follow-up visit. Twenty-seven percent were transferred from
      another facility after initial care, and 28% arrived intubated. Twenty-two
      percent were transported by helicopter, and 61% arrived intubated. Eighty percent
      of ventilated patients were extubated within 8 hours of admission, and all within
      24 hours. Average distance by helicopter transport was 57 miles, and cost
      $12,500.00. Large savings could be realized if patients cared for by local
      physicians were educated in basic burn care. This would be more palatable with
      good communication between the community hospital and burn center, with
      consultation on an as-needed basis.

PMID- 22878495
TI  - Burn center management of operating room fire injuries.
AB  - Approximately 100 operating room (OR) fires occur per year in the United States,
      with 15% resulting in serious injuries. Intraoperative cautery was frequently
      associated with OR fires before 1994; however, use of supplemental oxygen (O(2)),
      ethanol-based products, and disposable drapes have been more frequently
      associated with OR fires. Fires resulting from cosmetic and other small
      procedures involving use of nasal canula O(2) and electrocautery have been
      described in six published reports. We report five thermal injury cases admitted
      to our burn treatment center because of fires during surgical procedures over a 5
      year period. Two patients undergoing supraorbital excision experienced 2.5 and 3%
      TBSA involvement burns; in a third patient surgical excision of a nasal polyp
      resulted in a 1% TBSA burn; in a fourth patient an excisional biopsy of a lymph
      node resulted in a 2.75% TBSA burn; and the last patient was burned during
      placement of a pacemaker, with resulting TBSA of 10.5%. Two of the five patients
      required intubation for inhalational injury. Two patients required tangential
      excision and grafting of their thermal injuries. All patients had received local
      or parenteral anesthesia with supplemental O(2)/nitrous oxide (N(2)O) for
      surgical procedure. There are a number of ignition sources in the OR, including
      electrocautery, lasers, and faulty OR equipment. The risk of OR fires increases
      with surgical procedures involving the face and neck, including tracheostomy and
      tracheobronchial surgery. The common use of O(2)/N(2)O mixtures or enriched O(2)
      for minimally complex surgical procedures and disposable drapes adds to the risk
      of an OR fire: the O(2)/N(2)O provides a fuel source, and the disposable drapes
      trap thedelivered gas. Electrocautery near an O(2)/N(2)O source resulted in the
      five thermal injuries and warrants careful reconsideration of technique for
      surgical procedures.

PMID- 22878496
TI  - Takotsubo cardiomyopathy caused by severe burn injury.
AB  - The purpose of this report is to describe the clinical course of a 12% TBSA burn
      injury with takotsubo cardiomyopathy and to discuss this lesser known diagnosis.
      The authors performed a case study with retrospective chart review and conducted
      a literature search. Takotsubo cardiomyopathy is characterized by severe left
      ventricular dysfunction that is incited by severe psychological or physical
      stress. The patient's treatment course was complicated by the underlying
      cardiomyopathy requiring intubation, volume expansion, and vasoactive
      medications. After treatment for her burn injuries, her cardiac myopathy
      resolved, and she was discharged home. Takotsubo cardiomyopathy may be
      precipitated by burn injury. Treatment is supportive, but it should be instituted
      quickly to avoid complications.

PMID- 22878497
TI  - Review of burn research for the year 2010.
AB  - Like the previous year, 2010 was another active year for research in burn care.
      For this year, more than 1200 burn-related articles were published on a diverse
      array of topics. In this review, we focus on innovative and impactful burn injury
      related research. As in the previous review, we group articles according to the
      following categories: critical care, infection, inhalation injury, epidemiology,
      psychology, wound characterization and treatment, nutrition and metabolism, pain
      and itch management, burn reconstruction, and rehabilitation. We have found that
      burn research continues to be prolific throughout the world and reflects the wide
      ranging and complex care requirements of burn survivors.

PMID- 22878498
TI  - Direct mapping of nuclear shell effects in the heaviest elements.
AB  - Quantum-mechanical shell effects are expected to strongly enhance nuclear binding
      on an "island of stability" of superheavy elements. The predicted center at
      proton number Z = 114, 120, or 126 and neutron number N = 184 has been
      substantiated by the recent synthesis of new elements up to Z = 118. However, the
      location of the center and the extension of the island of stability remain vague.
      High-precision mass spectrometry allows the direct measurement of nuclear binding
      energies and thus the determination of the strength of shell effects. Here, we
      present such measurements for nobelium and lawrencium isotopes, which also pin
      down the deformed shell gap at N = 152.

PMID- 22878499
TI  - Conformational control of the Ste5 scaffold protein insulates against MAP kinase
      misactivation.
AB  - Cells reuse signaling proteins in multiple pathways, raising the potential for
      improper cross talk. Scaffold proteins are thought to insulate against such
      miscommunication by sequestering proteins into distinct physical complexes. We
      show that the scaffold protein Ste5, which organizes the yeast mating mitogen
      activated protein kinase (MAPK) pathway, does not use sequestration to prevent
      misactivation of the mating response. Instead, Ste5 appears to use a conformation
      mechanism: Under basal conditions, an intramolecular interaction of the
      pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain
      blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced
      membrane binding of Ste5 triggers release of this autoinhibition. Thus, in
      addition to serving as a conduit guiding kinase communication, Ste5 directly
      receives input information to decide if and when signal can be transmitted to
      mating output.

PMID- 22878500
TI  - Loss of the tumor suppressor BAP1 causes myeloid transformation.
AB  - De-ubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with
      increased risk of mesothelioma and uveal melanoma. Somatic BAP1 mutations occur
      in various malignancies. We show that mouse Bap1 gene deletion is lethal during
      embryogenesis, but systemic or hematopoietic-restricted deletion in adults
      recapitulates features of human myelodysplastic syndrome (MDS). Knockin mice
      expressing BAP1 with a 3xFlag tag revealed that BAP1 interacts with host cell
      factor-1 (HCF-1), O-linked N-acetylglucosamine transferase (OGT), and the
      polycomb group proteins ASXL1 and ASXL2 in vivo. OGT and HCF-1 levels were
      decreased by Bap1 deletion, indicating a critical role for BAP1 in stabilizing
      these epigenetic regulators. Human ASXL1 is mutated frequently in chronic
      myelomonocytic leukemia (CMML) so an ASXL/BAP1 complex may suppress CMML. A BAP1
      catalytic mutation found in a MDS patient implies that BAP1 loss of function has
      similar consequences in mice and humans.

PMID- 22878501
TI  - Adaptive sleep loss in polygynous pectoral sandpipers.
AB  - The functions of sleep remain elusive. Extensive evidence suggests that sleep
      performs restorative processes that sustain waking brain performance. An
      alternative view proposes that sleep simply enforces adaptive inactivity to
      conserve energy when activity is unproductive. Under this hypothesis, animals may
      evolve the ability to dispense with sleep when ecological demands favor
      wakefulness. Here, we show that male pectoral sandpipers (Calidris melanotos), a
      polygynous Arctic breeding shorebird, are able to maintain high neurobehavioral
      performance despite greatly reducing their time spent sleeping during a 3-week
      period of intense male-male competition for access to fertile females. Males that
      slept the least sired the most offspring. Our results challenge the view that
      decreased performance is an inescapable outcome of sleep loss.

PMID- 22878503
TI  - Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's
      jelly, and umbilical cord blood for treating spinal cord injuries in dogs.
AB  - Previous animal studies have shown that transplantation of mesenchymal stem cells
      (MSCs) into spinal cord lesions enhances axonal regeneration and promotes
      functional recovery. We isolated the MSCs derived from fat, bone marrow,
      Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and
      negative for hematopoietic cell markers. Their effects on the regeneration of
      injured canine spinal cords were compared. Spinal cord injury was induced by
      balloon catheter compression. Dogs with injured spinal cords were treated with
      only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov
      scores, immunohistochemistry, ELISA and Western blot analysis were used to
      evaluate the therapeutic effects. The different MSC groups showed significant
      improvements in locomotion at 8 weeks after transplantation (P<0.05). This
      recovery was accompanied by increased numbers of surviving neuron and
      neurofilament-positive fibers in the lesion site. Compared to the control, the
      lesion sizes were smaller, and fewer microglia and reactive astrocytes were found
      in the spinal cord epicenter of all MSC groups. Although there were no
      significant differences in functional recovery among the MSCs groups, UCB-derived
      MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity
      (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2
      levels, which may have promoted neuronal regeneration in the spinal cord. Our
      data suggest that transplantation of MSCs promotes functional recovery after SCI.
      Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection
      and less inflammation compared to other MSCs.

PMID- 22878502
TI  - Highly conserved protective epitopes on influenza B viruses.
AB  - Identification of broadly neutralizing antibodies against influenza A viruses has
      raised hopes for the development of monoclonal antibody-based immunotherapy and
      "universal" vaccines for influenza. However, a substantial part of the annual flu
      burden is caused by two cocirculating, antigenically distinct lineages of
      influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071,
      and CR9114, that protect mice against lethal challenge from both lineages.
      Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head
      region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved
      epitope in the HA stem and protects against lethal challenge with influenza A and
      B viruses. These antibodies may inform on development of monoclonal antibody
      based treatments and a universal flu vaccine for all influenza A and B viruses.

PMID- 22878504
TI  - Prevalence of Streptococcus suis genotypes in isolates from porcine endocarditis
      in East Japan.
AB  - Streptococcus suis is an important pathogen for both swine and humans. In this
      study, we genotyped 105 S. suis isolates from porcine endocarditis in East Japan
      on the basis of profiles of capsular serotype-specific, virulence-associated and
      pilus-associated genes. The most common genotype was cps2J/mrp+/epf-/sly-/sbp2
      /sep1-/sgp1+ (76.19%), followed by nt(non-typeable)/mrp+/epf-/sly-/sbp2-/sep1
      /sgp1+ (7.62%) and cps2J/mrp+/epf+/sly+/sbp2+/sep1-/sgp1- (7.62%). The
      representative isolates of mrp+/epf-/sly-/sbp2-/sep1-/sgp1+ were classified into
      ST28 complex, a clonal complex previously referred to as ST27 complex, whereas
      those of mrp+/epf+/sly+/sbp2+/sep1-/sgp1- were classified into ST1 complex by
      multilocus sequence typing. Because the majority of human clinical isolates were
      assigned to ST1 and ST28 complexes, most isolates from porcine endocarditis
      investigated in this study may have the potential to cause S. suis infection in
      humans.

PMID- 22878505
TI  - Clinical observation of patients with Fabry disease after switching from
      agalsidase beta (Fabrazyme) to agalsidase alfa (Replagal).
AB  - PURPOSE: Fabry disease is a rare, X-linked, inherited lysosomal storage disorder
      that can be treated with the enzymes agalsidasealfa (Replagal) and agalsidase
      beta (Fabrazyme). Currently, there is a global shortage of agalsidase beta, and
      this has increased global demand for agalsidase alfa. We assess the feasibility
      of switching patients on agalsidase beta treatment to agalsidase alfa instead.
      METHODS: This analysis is part of an ongoing observational study involving 11
      patients with Fabry disease in whom the treatment was switched from agalsidase
      beta (1 mg/kg every other week) to agalsidase alfa (0.2 mg/kg every other week).
      Data were collected for a minimum of 36 months: 24 months before and 12 months
      after the switch. Serial data were evaluated with respect to renal function,
      cardiac mass, pain, quality of life, and tolerability/safety. RESULTS: Indexes of
      renal function (estimated glomerular filtration rate) and cardiac mass (left
      ventricular mass index), pain (Brief Pain Inventory), and quality of life
      (EuroQoL-Dimensions) clearly showed that, in patients switched to agalsidase
      alfa, Fabry disease stabilized during the 12 months of follow-up. CONCLUSION:
      Despite the limitations of this preliminary observational study, it was found
      that all the patients maintained disease stability when treated with agalsidase
      alfa, as evidenced by estimated glomerular filtration rate, left-ventricular mass
      index,pain scores, and quality-of-life indexes, throughout 12 months of follow
      up.

PMID- 22878506
TI  - Survival among people with Down syndrome: a nationwide population-based study in
      Denmark.
AB  - PURPOSE: Several studies have shown substantially longer survival among persons
      with Down syndrome in recent decades. We examined survival patterns among Danish
      persons with Down syndrome by karyotype. METHODS: A national cohort of 3,530
      persons with Down syndrome identified from the Danish Cytogenetic Register and a
      reference cohort of persons without Down syndrome randomly selected from the
      general population were followed from 1 April 1968 to 15 January 2009 by linkages
      to the Register of Causes of Death and the Civil Registration System. RESULTS:
      Overall, persons with Down syndrome had higher mortality than the reference
      cohort but to a lesser degree for persons with mosaic trisomy 21 than for persons
      with standard trisomy 21 or with Robertsonian translocations (hazard ratio 4.98
      (95% confidence interval 3.51-7.08), 8.94 (8.32-9.60), and 10.23 (7.50-13.97),
      respectively). Among persons with Down syndrome born after April 1968, more
      recent birth cohorts had lower mortality rates than older birth cohorts, which
      was largely due to declining mortality among persons with Down syndrome who also
      had congenital heart defects. CONCLUSION: Recent birth cohorts of persons with
      Down syndrome experienced declining mortality, likely due to treatment for
      congenital heart defects, and persons with mosaic trisomy 21 had better survival
      than persons with other Down syndrome karyotypes.

PMID- 22878507
TI  - Incidental copy-number variants identified by routine genome testing in a
      clinical population.
AB  - PURPOSE: Mutational load of susceptibility variants has not been studied on a
      genomic scale in a clinical population, nor has the potential to identify these
      mutations as incidental findings during clinical testing been systematically
      ascertained. METHODS: Array comparative genomic hybridization, a method for
      genome-wide detection of DNA copy-number variants, was performed clinically on
      DNA from 9,005 individuals. Copy-number variants encompassing or disrupting
      single genes were identified and analyzed for their potential to confer
      predisposition to dominant, adult-onset disease. Multigene copy-number variants
      affecting dominant, adult-onset cancer syndrome genes were also assessed.
      RESULTS: In our cohort, 83 single-gene copy-number variants affected 40 unique
      genes associated with dominant, adult-onset disorders and unrelated to the
      patients' referring diagnoses (i.e., incidental) were found. Fourteen of these
      copy-number variants are likely disease-predisposing, 25 are likely benign, and
      44 are of unknown clinical consequence. When incidental copy-number variants
      spanning up to 20 genes were considered, 27 copy-number variants affected 17
      unique genes associated with dominant, adult-onset cancer predisposition.
      CONCLUSION: Copy-number variants potentially conferring susceptibility to adult
      onset disease can be identified as incidental findings during routine genome-wide
      testing. Some of these mutations may be medically actionable, enabling disease
      surveillance or prevention; however, most incidentally observed single-gene copy
      number variants are currently of unclear significance to the patient.

PMID- 22878508
TI  - Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy
      in Pompe disease.

PMID- 22878509
TI  - Identification of constitutional MLH1 epimutations and promoter variants in
      colorectal cancer patients from the Colon Cancer Family Registry.
AB  - PURPOSE: Constitutional MLH1 epimutations manifest as promoter methylation and
      silencing of the affected allele in normal tissues, predisposing to Lynch
      syndrome-associated cancers. This study investigated their frequency and
      inheritance. METHODS: A total of 416 individuals with a colorectal cancer showing
      loss of MLH1 expression and without deleterious germline mutations in MLH1 were
      ascertained from the Colon Cancer Family Registry (C-CFR). Constitutive DNA
      samples were screened for MLH1 methylation in all 416 subjects and for promoter
      sequence changes in 357 individuals. RESULTS: Constitutional MLH1 epimutations
      were identified in 16 subjects. Of these, seven (1.7%) had mono- or hemi-allelic
      methylation and eight had low-level methylation (2%). In one subject the
      epimutation was linked to the c.-27C>A promoter variant. Testing of 37 relatives
      from nine probands revealed paternal transmission of low-level methylation
      segregating with a c.+27G>A variant in one case. Five additional probands had a
      promoter variant without an MLH1 epimutation, with three showing diminished
      promoter activity in functional assays. CONCLUSION: Although rare, sequence
      changes in the regulatory region of MLH1 and aberrant methylation may alone or
      together predispose to the development of cancer. Screening for these changes is
      warranted in individuals who have a negative germline sequence screen of MLH1 and
      loss of MLH1 expression in their tumor.Genet Med 2013:15(1):25-35.

PMID- 22878510
TI  - Emotional functioning of patients with neurofibromatosis tumor suppressor
      syndrome.
AB  - PURPOSE: Although patients with neurofibromatosis are predisposed to multiple
      nerve sheath tumors that can develop anywhere in the body and cause significant
      morbidity (e.g., hearing loss; pain), little research has examined emotional
      correlates of neurofibromatosis. The purpose of this study was to examine
      emotional functioning among adult patients with neurofibromatosis. METHODS: A
      total of 248 patients with neurofibromatosis (neurofibromatosis 1,
      neurofibromatosis 2, or schwannomatosis) who received care at a specialized
      clinic completed validated measures to assess symptoms of depression and anxiety,
      level of perceived stress, and self-esteem. RESULTS: Patients with
      neurofibromatosis reported significantly more symptoms of depression and anxiety,
      higher levels of perceived stress, and lower levels of self-esteem as compared
      with general population norms. No significant differences were found among
      patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis, and
      emotional functioning was not significantly associated with disease severity.
      However, increased symptoms of depression and anxiety, higher levels of perceived
      stress, and lower levels of self-esteem were associated with a higher frequency
      of self-reported medical visits in the past year (P values <=0.05). CONCLUSION:
      Neurofibromatosis appears to be associated with reduced emotional functioning.
      Although further research is needed, these findings suggest a role for a
      multidisciplinary treatment approach to address emotional distress among adult
      patients with neurofibromatosis.

PMID- 22878511
TI  - Toward validation of a minimal competence core of morphosyntax for African
      American children.
AB  - PURPOSE: The authors set out to determine (a) whether African American children's
      spontaneous spoken language met use criteria for a revised minimal competence
      core with original and added morphosyntactic patterns at different geographical
      locations, and (b) whether pass/fail status on this core was differentiated on
      other criterion measures of language maturity. METHOD: The authors used a common
      set of activities and stimuli to elicit spontaneous speech samples from Head
      Start students, age 3;0 (years; months). The 119 participants were distributed at
      a northern (Lansing, MI) and a southern (Baton Rouge, LA) location. RESULTS: More
      than 80% of the children at each location met criteria for 10 core competencies.
      They included sentence length, type, complexity, and morphosyntactic elaborations
      of sentences at the lexical, phrasal, and clausal levels. The 2 most significant
      predictors of pass/fail outcomes in a regression analysis were (a) clinical
      referral status and (b) the number of different words (NDW(100)) spoken in a
      speech sample. CONCLUSION: A minimal competence core analyses of spontaneous oral
      language samples may help to identify delayed spoken grammars in African American
      children.

PMID- 22878512
TI  - The contribution of two categories of parent verbal responsiveness to later
      language for toddlers and preschoolers on the autism spectrum.
AB  - PURPOSE: The authors examined longitudinal associations between 2 categories of
      parent verbal responsiveness and language comprehension and production 1 year
      later in 40 toddlers and preschoolers with a diagnosis of an autism spectrum
      disorder (ASD). METHOD: Parent-child play samples using a standard toy set were
      digitally captured and coded for child engagement with objects and communication
      acts and for parent verbal responses to play and communication. RESULTS: After
      controlling for parent education, child engagement, and initial language level,
      only parent directives for language that followed into the child's focus of
      attention accounted for unique variance in predicting both comprehension and
      production 1 year later. A series of exploratory analyses revealed that parent
      comments that followed into the child's focus of attention also accounted for
      unique variance in later comprehension and production for children who were
      minimally verbal at the initial time period. CONCLUSIONS: Child developmental
      level may warrant different types of linguistic input to facilitate language
      learning. Children with ASD who have minimal linguistic skills may benefit from
      parent language input that follows into the child's focus of attention. Children
      with ASD who are verbally fluent may need more advanced language input to
      facilitate language development.

PMID- 22878513
TI  - An evidence-based systematic review on communication treatments for individuals
      with right hemisphere brain damage.
AB  - PURPOSE: The purpose of this review is to evaluate and summarize the research
      evidence related to the treatment of individuals with right hemisphere
      communication disorders. METHOD: A comprehensive search of the literature using
      key words related to right hemisphere brain damage and communication treatment
      was conducted in 27 databases (e.g., PubMed, CINAHL). On the basis of a set of
      pre-established clinical questions, inclusion/exclusion criteria, and search
      parameters, studies investigating sentence- or discourse-level treatments were
      identified and evaluated for methodological quality. Data regarding participant,
      intervention, and outcome variables were reported. RESULTS: Only 5 studies were
      identified, each representing a different sentence- or discourse-level treatment
      approach and reporting a wide range of prosodic, expressive, receptive, and
      pragmatic outcomes. CONCLUSION: Although the state of the evidence pertaining to
      right hemisphere communication treatments is at a very preliminary stage, some
      positive findings were identified to assist speech-language pathologists who are
      working with individuals with right hemisphere brain damage. Clinical
      implications and recommendations for future research are explored.

PMID- 22878514
TI  - AbobotulinumtoxinA (Dysport) dosing in cervical dystonia: an exploratory analysis
      of two large open-label extension studies.
AB  - Treatment with botulinum toxin-A is recommended as first-line treatment for
      cervical dystonia (CD). In clinical practice many factors appear to influence
      dose adjustment and the retreatment regimen; however, there is little information
      available in the literature regarding the evolution of dosing over treatment
      cycles. We report on two similarly designed, long-term, multicenter, open-label
      extension studies of Dysport for the treatment of CD, which followed 500 U fixed
      dose placebo-controlled trials. Both studies specified a fixed 500 U dose for the
      first open-label treatment cycle, with dose adjustment in subsequent treatment
      cycles according to the clinical response. These analyses include 218 patients
      who entered the two studies; doses in the subsequent treatment cycles ranged
      between 250 and 1,000 U. During open-label treatment, all treatment cycles
      resulted in improvements in mean Toronto Western Spasmodic Torticollis Rating
      Scale (TWSTRS) total scores. However, increasing the dose of Dysport above the
      initial 500 U dose was not observed to result in an incremental improvement in
      response as measured by the TWSTRS. No individual patient characteristic was
      found to reliably predict the use of higher doses at each treatment cycle.
      Dysport was generally well tolerated with no major differences in the incidence
      of adverse events (AEs) observed with different doses. Dysphagia was considered
      an AE of special interest and dysphagia data from the open-label studies were
      combined with two Phase II studies. Analysis of this enhanced database indicates
      that unilateral injections of >150 U into the sternocleidomastoid muscle is
      associated with a higher dysphagia risk. Thus, limiting the dose in the
      sternocleidomastoid may help reduce the incidence of dysphagia.

PMID- 22878515
TI  - S(p)O(2) targets--how normal is normal?

PMID- 22878517
TI  - Medical innovation--a starting point for plastic surgeons.

PMID- 22878518
TI  - [Thyroid storm].
AB  - Thyroid storm is a complicated, life-threatening form of thyrotoxicosis. The
      causes are multifactorial and elevated iodothyronine levels are only one of many
      components. Usually, the transition from thyrotoxicosis to thyroid storm is
      ignited by non-thyroidal triggers. This is a rare condition observed with an
      incidence between 0.8 and 1.4 cases per 100,000 inhabitants. Diagnosis relies
      primarily on clinical criteria. Multimodal therapy aims at disrupting positive
      feedback loops between elevated levels of free T3 or T4 and their effects on
      target tissues and organs. Timely diagnosis and therapy help to reduce mortality
      to below 35%.

PMID- 22878519
TI  - A phase I study of BMS-690514 in Japanese patients with advanced or metastatic
      solid tumors.
AB  - PURPOSE: BMS-690514 is a novel oral tyrosine kinase inhibitor of ErbB and
      vascular endothelial growth factor receptor. This open-label phase I dose
      escalation study (ClinicalTrials.gov Identifier: NCT00516451) aimed to assess the
      safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics of BMS
      690514 in Japanese patients with advanced or metastatic solid tumors. METHODS:
      Patients with advanced or metastatic solid tumors received oral BMS-690514 once
      daily continuously until disease progression or intolerable toxicity occurred.
      Dose-limiting toxicity (DLT) was evaluated from the first dose to Day 29. Dose
      levels at 100 and 200 mg were investigated. Assessments included adverse events,
      tumor response, pharmacokinetics, pharmacodynamics, 2 [18F] fluoro-2-deoxyglucose
      positron-emitting tomography, and epidermal growth factor receptor and K-ras
      mutations. RESULTS: BMS-690514 at the dose of 100 mg (n = 3) or 200 mg (n = 3)
      was administered once daily to totally nine patients and was well tolerated up to
      200 mg. No treatment-related serious adverse events or DLTs were reported.
      Frequently observed treatment-related AEs were acne, diarrhea, dry skin,
      hypertension, stomatitis, blood fibrinogen increased, hemoglobin decreased,
      pruritus, and hypoalbuminemia. These were generally reported as Grade 1 and 2.
      Five of 9 patients (56 %) had stable disease. Plasma concentrations of BMS-690514
      reached Cmax within 3 h and declined with an effective half-life of approximately
      10 and 12 h at 100 and 200 mg, respectively. CONCLUSIONS: Oral BMS-690514 was
      well tolerated in Japanese patients with advanced or metastatic solid tumors up
      to 200 mg.

PMID- 22878520
TI  - A single supratherapeutic dose of ridaforolimus does not prolong the QTc interval
      in patients with advanced cancer.
AB  - PURPOSE: This dedicated QTc study was designed to evaluate the effect of the
      mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in
      patients with advanced malignancies. METHODS: We conducted a fixed-sequence,
      single-blind, placebo-controlled study. Patients (n = 23) received placebo on day
      1 and a single 100-mg oral dose of ridaforolimus on day 2 in the fasted state.
      Holter electrocardiogram (ECG) monitoring was performed for 24 h after each
      treatment, and blood ridaforolimus concentrations were measured for 24 h after
      dosing. The ECGs were interpreted in a blinded fashion, and the QT interval was
      corrected using Fridericia's formula (QTcF). After a washout of at least 5 days,
      22 patients went on to receive a therapeutic regimen of ridaforolimus (40 mg
      orally once daily for 5 days per week). RESULTS: The upper limit of the two-sided
      90 % confidence interval for the placebo-adjusted mean change from baseline in
      QTcF was <10 ms at each time point. No patient had a QTcF change from baseline
      >30 ms or QTcF interval >480 ms. Geometric mean exposure to ridaforolimus after
      the single 100-mg dose was comparable to previous experience with the therapeutic
      regimen. There appeared to be no clear relationship between individual QTcF
      change from baseline and ridaforolimus blood concentrations. Ridaforolimus was
      generally well tolerated, with adverse events consistent with prior studies.
      CONCLUSIONS: Administration of the single 100-mg dose of ridaforolimus did not
      cause a clinically meaningful prolongation of QTcF, suggesting that patients
      treated with ridaforolimus have a low likelihood of delayed ventricular
      repolarization.

PMID- 22878521
TI  - Persistent median artery (palmar type) and median nerve block in the forearm:
      observational study of prevalence.
AB  - BACKGROUND: We sought to define the crude prevalence rate of the persistent
      median artery (PMA) (palmar type). Although there is no reported case in the
      anesthetic literature, a few sporadic case reports and series reported in
      anatomical and orthopedic journals describe an incidence of between 1.5% and
      27.1%. METHODS: We conducted a prospective observational study to define the
      crude prevalence of the PMA (palmar type) by scanning 100 forearms of 50
      volunteers using a high-frequency ultrasound probe. RESULTS: We found 19 PMAs in
      13 individuals, thus giving a prevalence of 19%. Other arterial variants were
      also identified within this population. CONCLUSIONS: Anatomical variations of the
      blood supply to the forearm and hand can be identified with available high
      frequency ultrasound equipment. Arterial variants immediately adjacent to the
      median nerve may occur in approximately 1 in 5 limbs. Practitioners should
      actively seek their presence or absence.

PMID- 22878522
TI  - The sensory territory of the lateral cutaneous nerve of the thigh as determined
      by anatomic dissections and ultrasound-guided blocks.
AB  - BACKGROUND AND OBJECTIVES: A femoral block sometimes fails to provide complete
      sensory anesthesia of the anterior aspect of middle and distal thigh, and a block
      of the lateral cutaneous nerve of the thigh (LCN) is often necessary to
      supplement it. The goal of this study was to demonstrate, both in the anatomy
      laboratory and in the clinical setting, a possible contribution of the LCN to the
      innervation of the anterior thigh. METHODS: This was a prospective, observational
      study, including anatomic dissections and a clinical section in which 22 patients
      received an ultrasound-guided block of the LCN. The resulting area of anesthesia
      was determined 15 minutes later using pinprick examination. RESULTS: In 1 of 3
      thigh dissections, we found a dominant LCN innervating most of the anterior
      aspect of the middle and distal thigh, areas that are usually attributed to the
      femoral nerve. In the clinical part of the study, 10 patients (45.5%) developed
      an area of anesthesia that extended to the medial aspect of the thigh and
      distally to the patella. CONCLUSIONS: Our results, coming from a small sample,
      seem to indicate that the LCN may contribute to the innervation of the anterior
      thigh in some cases. A block of the LCN could be considered when a femoral block
      has failed to produce the expected area of anesthesia.

PMID- 22878523
TI  - Brachial plexus root injection in a human cadaver model: injectate distribution
      and effects on the neuraxis.
AB  - BACKGROUND: The potential for injection into the brachial plexus root at cervical
      levels must be considered during interscalene block or chronic pain interventions
      in the neck, but this phenomenon has not been well studied. In this
      investigation, we performed injections into the brachial plexus roots of
      unembalmed cadavers, with real-time ultrasound guidance, to evaluate the proximal
      and distal spread of the injected fluids, the potential of the injectate to reach
      the neuraxis, and whether the injectate could migrate into the actual substance
      of the spinal cord itself. METHODS: A solution of particulate dye mixed with
      local anesthetic was injected into 8 brachial plexus roots at a lower cervical
      level, in unembalmed cadaver specimens, utilizing an automated pump and pressure
      monitor. Two injections were made adjacent to nerve roots as controls. The
      specimens were then dissected, and gross and microscopic analysis utilized to
      determine the distribution of the dye and the structures affected. RESULTS: The
      mean peak pressure achieved during plexus root injections was 48.9 psi. After
      injections into the plexus root, dye was evident within the neural tissue at the
      level of injection and spread primarily distally in the plexus. In 1 of 8
      injections into the brachial plexus root, the dye in the injectate spread
      proximally into the spinal canal, but in none of the injections was the spinal
      cord affected by the dye. CONCLUSIONS: Injection directly into the neural tissue
      of a brachial plexus root in a cadaver model produced high pressures suggestive
      of intrafascicular injection and widespread flow of the injectate through the
      distal brachial plexus. However, proximal movement of the dye-containing
      injectate was more restricted, with only 1 of the injections leading to epidural
      spread and no apparent effects on the spinal cord.

PMID- 22878524
TI  - Intrathecal oxytocin inhibits visceromotor reflex and spinal neuronal responses
      to noxious distention of the rat urinary bladder.
AB  - BACKGROUND AND OBJECTIVES: Oxytocin (OXY) is a neuropeptide that has recently
      been recognized as an important component of descending analgesic systems. The
      present study sought to determine if OXY produces antinociception to noxious
      visceral stimulation. METHODS: Urethane-anesthetized female rats had intrathecal
      catheters placed acutely, and the effect of intrathecal OXY on visceromotor
      reflexes (VMRs; abdominal muscular contractions quantified using electromyograms)
      to urinary bladder distension (UBD; 10-60 mm Hg, 20 seconds; transurethral
      intravesical catheter) was determined. The effect of OXY applied to the surface
      of exposed spinal cord was determined in lumbosacral dorsal horn neurons excited
      by UBD using extracellular recordings. RESULTS: Oxytocin doses of 0.15 or 1.5 MUg
      inhibited VMRs to UBD by 37% +/- 8% and 68% +/- 10%, respectively. Peak
      inhibition occurred within 30 minutes and was sustained for at least 60 minutes.
      The effect of OXY was both reversed and prevented by the intrathecal
      administration of an OXY-receptor antagonist. Application of 0.5 mM OXY to the
      dorsum of the spinal cord inhibited UBD-evoked action potentials by 76% +/- 12%.
      Consistent with the VMR studies, peak inhibition occurred within 30 minutes and
      was sustained for greater than 60 minutes. CONCLUSIONS: These results argue that
      intrathecal OXY produces an OXY receptor-specific antinociception to noxious UBD,
      with part of this effect due to inhibition of spinal dorsal horn neurons. To our
      knowledge, these studies provide the first evidence that intrathecal OXY may be
      an effective pharmacological treatment for visceral pain.

PMID- 22878525
TI  - beta1 integrins restrict the growth of foci and spheroids.
AB  - Extracellular matrices (ECM) have important roles for tissue architecture, both
      as structural and signaling components. Members of the integrin family are the
      main regulators of ECM assembly and transmitters of signals from the ECM to
      cells. In this study, we have analyzed the role of integrin subunit beta1 in two
      dimensional (2D) and three-dimensional (3D) cell cultures using integrin beta1
      null cells (MEFbeta1(-/-) and GD25) and their beta1 integrin-expressing
      counterparts. GD25 and GD25beta1 cells proliferated with similar kinetics in sub
      confluent 2D cultures, whereas GD25 cells attained higher cell numbers in
      confluent culture and formed foci with fivefold higher frequency than GD25beta1
      cells. Fibronectin fibrils were abundantly deposited throughout the GD25beta1
      colonies but strictly limited to the central multilayered area (focus) of GD25
      colonies. During 3D growth as spheroids, GD25 continuously increased in size for
      >21 days while the growth of GD25beta1 spheroids ceased after 14 days. Similarly,
      MEFbeta1(-/-) cells formed foci and grew as spheroids, while the beta1 integrin
      expressing MEF did not. Expression levels of the cell cycle markers Ki67, PCNA,
      and histone H3-pSer10 were similar between GD25beta1 and GD25 spheroids.
      Apoptotic cells accumulated earlier in GD25 spheroids; however, cell death
      increased with spheroid volumes in both spheroid types. In both cell systems, the
      presence of beta1 integrins resulted in higher levels of active myosin light
      chain and inactive myosin light chain phosphatase, and a more compact spheroid
      structure. In conclusion, our results reveal that regulation of 3D growth in
      spheroids and foci is dependent on the beta1 subfamily of integrins, and suggest
      that myosin-based spheroid contraction in combination with cell death limits the
      growth of beta1-expressing spheroids.

PMID- 22878528
TI  - Maternal hypothyroxinemia during pregnancy and growth of the fetal and infant
      head.
AB  - Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth
      and corticogenesis. This study focused on the effect of maternal hypothyroxinemia
      during early pregnancy on growth of the fetal and infant head. In a population
      based birth cohort, we assessed thyroid status in early pregnancy (median 13.4,
      90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head
      size of their children at 5 time points. Hypothyroxinemia was defined as normal
      thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the
      10th percentile. Statistical analysis was performed using linear generalized
      estimating equation. Maternal hypothyroxinemia was associated with larger fetal
      and infant head size (overall estimate beta: 1.38, 95% confidence interval 0.56;
      2.19, P = .001). In conclusion, in the general population, even small variations
      in maternal thyroid function during pregnancy may affect the developing head of
      the young child.

PMID- 22878526
TI  - A simple method to obtain pure cultures of multiciliated ependymal cells from
      adult rodents.
AB  - Ependymal cells form an epithelium lining the ventricular cavities of the
      vertebrate brain. Numerous methods to obtain primary culture ependymal cells have
      been developed. Most of them use foetal or neonatal rat brain and the few that
      utilize adult brain hardly achieve purity. Here, we describe a simple and novel
      method to obtain a pure non-adherent ependymal cell culture from explants of the
      striatal and septal walls of the lateral ventricles. The combination of a low
      incubation temperature followed by a gentle enzymatic digestion allows the
      detachment of most of the ependymal cells from the ventricular wall in a period
      of 6 h. Along with ependymal cells, a low percentage (less than 6 %) of non
      ependymal cells also detaches. However, they do not survive under two restrictive
      culture conditions: (1) a simple medium (alpha-MEM with glucose) without any
      supplement; and (2) a low density of 1 cell/ul. This purification method strategy
      does not require cell labelling with antibodies and cell sorting, which makes it
      a simpler and cheaper procedure than other methods previously described. After a
      period of 48 h, only ependymal cells survive such conditions, revealing the
      remarkable survival capacity of ependymal cells. Ependymal cells can be
      maintained in culture for up to 7-10 days, with the best survival rates obtained
      in Neurobasal supplemented with B27 among the tested media. After 7 days in
      culture, ependymal cells lose most of the cilia and therefore the mobility, while
      acquiring radial glial cell markers (GFAP, BLBP, GLAST). This interesting fact
      might indicate a reprogramming of the cell identity.

PMID- 22878527
TI  - Retinol-binding protein 4 downregulation during osteogenesis and its localization
      to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a
      novel tissue function.
AB  - Craniosynostosis is a developmental disorder of the skull arising from premature
      bony fusion of cranial sutures, the sites of skull bone growth. In a recent gene
      microarray study, we demonstrated that retinol-binding protein 4 (RBP4) was the
      most highly downregulated gene in suture tissue during the pathological process
      of premature bony fusion. To gain insight into the function of RBP4 in cranial
      sutures, we analysed primary cells cultured from human cranial suture mesenchyme.
      These cells express RBP4 but not CRBP1, cellular retinol-binding protein 1, the
      typical cytoplasmic retinol storage protein. Using flow cytometry, we showed that
      suture mesenchymal cells express the RBP4 receptor, STRA6, on the cell surface.
      In a cell culture model of cranial osteogenesis, we found that RBP4 was
      significantly downregulated during mineralization, analogous to its decrease in
      pathological suture fusion. We found that cranial suture cells do not secrete
      detectable levels of RBP4, suggesting that it acts in a cell-autonomous manner.
      High-resolution confocal microscopy with a panel of antibody markers of
      cytoplasmic organelles demonstrated that RBP4 was present in several hundred
      cytoplasmic vesicles of about 300 nm in diameter which, in large part, were
      conspicuously distinct from the ER, the Golgi and endosomes of the endocytic
      pathway. We speculate that in suture mesenchymal cells, endogenous RBP4 receives
      retinol from STRA6 and the RBP4-retinol complex is stored in vesicles until
      needed for conversion to retinoic acid in the process of osteogenesis. This study
      extends the role of RBP4 beyond that of a serum transporter of retinol and
      implicates a broader role in osteogenesis.

PMID- 22878529
TI  - Tissue remodeling and nonendometrium-like menstrual cycling are hallmarks of
      peritoneal endometriosis lesions.
AB  - We identified differentially expressed genes comparing peritoneal endometriosis
      lesions (n = 18), eutopic endometrium (n = 17), and peritoneum (n = 22) from the
      same patients with complete menstrual cycles using microarrays (54 675 probe
      sets) and immunohistochemistry. Peritoneal lesions and peritoneum demonstrated
      3901 and 4973 significantly differentially expressed genes compared to eutopic
      endometrium, respectively. Peritoneal lesions significantly revealed no
      correlation with a specific menstrual cycle phase by gene expression and
      histopathology, exhibited low expressed proliferation genes, and constant levels
      of steroid hormone receptor genes. Tissue remodeling genes in cytoskeleton,
      smooth muscle contraction, cellular adhesion, tight junctions, and O-glycan
      biosynthesis were the most significant to lesions, including desmin and smooth
      muscle myosin heavy chain 11. Protein expression and location of desmin, alpha
      actin, and h-caldesmon in peritoneal lesions discriminated between smooth muscle
      hyperplasia and metaplasia. Peritoneal lesions demonstrate no menstrual cycle
      phasing but constant steroid hormone receptor expression where a slow but steady
      growth is linked with tissue remodeling. Our study contributes to the molecular
      pathology of peritoneal endometriosis and will help to identify clinical targets
      for treatment and management.

PMID- 22878530
TI  - Is NMR metabolic profiling of spent embryo culture media useful to assist in
      vitro human embryo selection?
AB  - OBJECT: The prediction of embryo viability by usual morphological analysis is
      currently unsatisfactory. New non-invasive techniques such as high-resolution
      nuclear magnetic resonance ((1)H-NMR) spectroscopy that allows assessment of
      metabolic profiling in spent culture media might help embryologists to predict
      embryo development. MATERIALS AND METHODS: Individual microdrops of culture media
      were analysed after 24 h of embryo culture (from day 3 to day 4) by spectroscopy
      using a 1 mm microliter probe allowing analysis without sample dilution. Embryos
      were divided into two groups on day 5: non-arrested embryos (n = 19) and arrested
      embryos unable to reach the blastocyst stage (n = 20). Multivariate analysis
      techniques such as Principal Component Analysis (PCA) and Orthogonal Partial
      Least Square Discriminant Analysis (OPLS-DA) were performed to compare
      extracellular metabolite balance. RESULTS: (1)H-NMR used in combination with a 1
      mm probe suggested that in vitro cultured human embryos that have a high
      developmental potential modify their environment slightly compared to embryos
      that cease to develop. However, differences between the two groups did not reach
      statistical significance and multivariate statistical analysis did not allow
      clustering of the two groups. CONCLUSION: This study indicated that this
      technique would not be sufficiently powerful alone to provide information that
      might help to assess the developmental potential of individual embryos for in
      vitro fertilisation (IVF).

PMID- 22878531
TI  - Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and
      women as defined by WHO criteria.
AB  - This study sought to determine the association between calcaneal quantitative
      ultrasound (QUS) and fracture risk in individuals without osteoporosis according
      to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found
      that calcaneal QUS is an independent predictor of fracture risk in women with non
      osteoporotic bone mineral density (BMD). INTRODUCTION: More than 50 % of women
      and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic
      threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This
      study aimed to test the hypothesis that low calcaneal QUS is associated with
      increased fracture risk in individuals with non-osteoporotic BMD. METHODS: We
      included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at
      femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the
      calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by
      dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The
      incidences of any fragility fracture were ascertained by X-ray reports during the
      follow-up period from 1994 to 2011. RESULTS: Of the 702 participants, 26 % of
      women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one
      fragility fracture during the follow-up period. In women, after adjusting for
      covariates, increased risk of any fracture was significantly associated with
      decreased BUA (HR = 1.50; 95 % CI, 1.13-1.99). Compared with that of FNBMD, the
      models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and
      vertebral fracture, respectively), and yielded a net reclassification improvement
      of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly
      associated with fracture risk before and after adjustment. CONCLUSION: These
      results suggest that calcaneal BUA is an independent predictor of fracture risk
      in women with non-osteoporotic BMD.

PMID- 22878532
TI  - Synthesis and characterization of new ruthenium N-heterocyclic carbene Hoveyda II
      type complexes. Study of reactivity in ring closing metathesis reactions.
AB  - This manuscript describes the synthesis and structural study of new second
      generation Hoveyda-Grubbs catalysts: 1,3-dimesityl-acenaphthylenyl-4,5-imidazolin
      2-ylidene (BIAN-NHC) ruthenium isopropoxybenzylidene dichloride and 1,3-bis(2,6
      dimethylphenyl)-2,3-dihydro-1H-imidazole Cl(2)Ru(=CH-o-O-i-PrC(6)H(4)) . The
      electrochemical and catalytic behavior of these new complexes was compared with
      the conventional NHC carbene Hoveyda II IMes-type complexes and for ring closing
      metathesis reactions.

PMID- 22878533
TI  - The role of rifaximin in the primary prophylaxis of spontaneous bacterial
      peritonitis in patients with liver cirrhosis.
AB  - BACKGROUND: Primary prophylaxis of spontaneous bacterial peritonitis (SBP) may
      provide a survival advantage in cirrhotic patients with ascites and has become an
      integral part of clinical practice. Rifaximin is a poorly absorbable antibiotic
      with a broad spectrum of antibacterial action and has low risk of introducing
      bacterial resistance. AIM: To determine whether rifaximin is associated with
      decreasing the risk of SBP and improving transplant-free survival in cirrhotic
      patients with ascites. METHODS: The medical records of all adult patients with
      liver cirrhosis and large ascites justifying paracentesis evaluated in our clinic
      (2003 to 2007) were reviewed. Patients were stratified into 2 groups by the use
      of rifaximin. Patients were excluded if they had received another antibiotic for
      SBP prophylaxis or had a history of SBP before rifaximin therapy. RESULTS: A
      total of 404 patients were included, of whom 49 (12%) received rifaximin. The
      rifaximin and nonrifaximin groups were comparable with regards to age, sex, and
      race. The median follow-up time was 4.2 [1.0, 17.1] months. During this time
      period, 89% of patients on rifaximin remained SBP free compared with 68% of those
      not on rifaximin (P=0.002). After adjusting for Model of End-Stage Liver Disease
      score, Child-Pugh score, serum sodium, and ascitic fluid total protein, there was
      a 72% reduction in the rate of SBP in the rifaximin group (hazard ratio=0.28; 95%
      confidence interval, 0.11-0.71; P=0.007). The group treated with rifaximin also
      demonstrated a transplant-free survival benefit compared with those not on
      rifaximin (72% vs. 57%, P=0.045). CONCLUSIONS: Intestinal decontamination with
      rifaximin may prevent SBP in cirrhotic patients with ascites. Prospective
      randomized controlled trials are needed to confirm this finding.

PMID- 22878534
TI  - Characteristics of mothers with depressive symptoms outside the postpartum
      period.
AB  - Numerous studies have investigated the deleterious effects of maternal depression
      on child outcomes. Knowledge of characteristics of these mothers is incomplete,
      as most studies utilize small samples or limit investigation to the postpartum
      period. Utilizing data from a nationally representative sample of 7,211 fathers
      and mothers living in households with children aged 5-17 years who participated
      in the Medical Expenditure Panel Survey (MEPS) 2004-2006, the Patient Health
      Questionnaire-2 (PHQ-2) was used to assess parental depressive symptoms, the
      Short Form-12 (SF-12) was used to examine paternal and maternal physical health,
      and the Columbia Impairment Scale was used to measure child behavioral or
      emotional problems. In multivariate analyses, maternal unemployment (AOR 1.76, 95
      % CI 1.31-2.35); living with smokers (AOR 1.82, 95 % CI 1.12-2.94); poor maternal
      physical health (AOR 2.31; 95 % CI 1.81-2.94); living with children with
      behavioral or emotional problems (AOR 2.95, 95 % CI 2.30-3.96); and paternal
      depressive symptoms (AOR 5.11, 95 % CI 1.97-13.25) each were independently
      associated with increased rates of maternal depressive symptoms. This paper is
      the first we are aware of to use a nationally representative sample to
      investigate characteristics associated with maternal depressive symptoms and
      found that maternal unemployment, living with smokers, poor maternal physical
      health, having children with behavioral or emotional problems, and paternal
      depressive symptoms are each independently associated with maternal depressive
      symptoms. In these data, paternal depressive symptoms are associated with the
      greatest risk of mothers exhibiting depressive symptoms, a finding that we
      believe has never before been shown.

PMID- 22878535
TI  - Two cases of feline orbital aspergillosis due to Aspergillus udagawae and A.
      viridinutans.
AB  - Aspergillus udagawae and A. viridinutans are members of the section Fumigati;
      both cause invasive aspergillosis in humans. These two Aspergillus species are
      discriminated from A. fumigatus by molecular methods. Herein, we report two cases
      of feline orbital aspergillosis, one caused by A. udagawae and the other by A.
      viridinutans. To our knowledge, Case 1 represents the first reported case of
      treatment of A. udagawae with a high dosage of itraconazole, and Case 2
      represents the first reported case of A. viridinutans infection associated with
      sarcoma. Identification of the etiologic agents of these cases was confirmed by
      comparative analyses of the sequences of beta-tubulin-encoding genes. With the
      spread of non-fumigatus aspergillosis, increasing emphasis should be placed on
      molecular identification of the infecting Aspergillus species and the use of in
      vitro drug susceptibility tests to ensure the selection of appropriate
      antibiotics.

PMID- 22878536
TI  - Hormonal differences in peripheral blood and gene profiling in the liver and
      lymphocytes in Japanese black cattle with growth retardation.
AB  - Japanese Black cattle occasionally demonstrate growth retardation despite
      sufficient nutrient intake. To clarify hormonal and transcriptional
      characteristics, we investigated differences in blood components, including
      hormones, and differences in exhaustive gene expressions in the liver and
      peripheral lymphocytes of six cattle with growth retardation (GR cattle) and
      eight control cattle of the same age and pedigree with normal growth. Hematocrit
      values and concentrations of hemoglobin, serum albumin, total cholesterol,
      insulin-like growth factor 1 (IGF-1), thyroxine and insulin in GR cattle were
      significantly lower than those in controls. GR cattle also excreted higher levels
      of GH. We used three GR and three control cattle for a microarray analysis in the
      liver and found that 279 gene expressions were significantly different. However,
      gene expressions related to the GH-IGF-1 axis, such as the GH receptor and IGF-1,
      were not significantly different from those of controls. Immune-related gene
      expressions were significantly lower. To clarify these gene expression levels,
      peripheral lymphocytes were used for real-time RT-PCR. The expression rates of
      genes that were significantly lower in the liver, such as chemokine ligand 8,
      interferon gamma receptor 1 and immunoglobulin light chain VJ region were also
      significantly lower in three GR cattle than those in the three control cattle.
      These results suggest that the cause of growth retardation in the present study
      was due to other factors, not abnormal gene expressions of factors related to the
      GH-IGF-1 axis in the liver, and that GR cattle were susceptible to infectious
      disease.

PMID- 22878537
TI  - Scanning electron microscopic study of the vascular system in the hemal node of
      the bovine cervical region.
AB  - The vasculature of the hemal node (HN) from the bovine cervical region was
      investigated using a combination of vascular corrosion casting and scanning
      electron microscopy. A dense vessel network of capsule was found surrounding the
      cast of HN parenchyma and had no connection with the subcapsular sinus; these
      vessels converged and exited the HN via the hilar vein. Within the HN, many
      anastomoses were found between the capillary networks and the surrounding sinuses
      in the follicular zone and deep cortex. The sinusoid pathway in the HN was
      characterized by subcapsular sinuses, which were continuous with the trabecular
      sinuses and tubular sinuses over the parenchyma, and these sinuses finally
      entered the medullary veins. In our study, direct communications between cortical
      capillaries and subcapsular sinuses were identified. This may explain the origin
      of numerous erythrocytes in the HN sinusoids and help to understand lymphocyte
      migration of the HN.

PMID- 22878538
TI  - Existence of Galphai2-expressing axon terminals in the goat main olfactory bulb.
AB  - In rodents, Galpha(i2)-expressing sensory neurons (SNs) that co-express
      vomeronasal receptor type 1 (V1R) are specifically found in the vomeronasal organ
      (VNO) and project their axons to the accessory olfactory bulb (AOB). In goats,
      however, Galpha(i2)/V1R-expressing SNs exist in both the VNO and the olfactory
      epithelium. Thus, we examined whether the Galpha(i2)-expressing axons
      functionally project to the main olfactory bulb (MOB). We analyzed the expression
      of Galpha(i2) in the olfactory bulb and found small Galpha(i2)-immunoreactive
      clusters in the MOB. The Galpha(i2)-immunoreactive axons in these clusters made
      synaptic contacts with second-order neurons in the MOB. These results suggest
      that some Galpha(i2)-expressing SNs functionally project their axons to the MOB
      in goats.

PMID- 22878539
TI  - Influence of the injection site on the pharmacokinetics of cefquinome following
      intramuscular injection in piglets.
AB  - The aim of the present study was to investigate the influence of different
      injection sites, i.e., the neck area and thigh muscle, on the pharmacokinetics of
      cefquinome in piglets following intramuscular (i.m.) injection. Cross-bred
      (Landrace * Duroc * Yorkshire) piglets were administered the same dose of
      cefquinome (2 mg/kg body weight) via intravenous injection and intramuscular
      injection into the neck area or thigh. The mean maximum concentrations (C(max))
      of cefquinome following i.m. injection into neck or thigh area were 4.62 +/- 0.31
      MUg/ml at 0.38 +/- 0.14 hr and 4.39 +/- 0.53 MUg/ml at 0.42 +/- 0.13 hr,
      respectively. The absolute bioavailabilities (F) of cefquinome after i.m.
      injection into the neck or thigh area were 103.04 +/- 13.01 and 97.56 +/- 16.14%,
      respectively (P>0.05). There were no differences noted between the two different
      injection sites for the pharmacokinetic properties of cefquinome after i.m.
      injection in piglets. Further studies will be needed to determine the incidence
      or severity of injection site reactions following repeated administrations of
      cefquinome into both injection sites.

PMID- 22878540
TI  - Survey on tick-borne pathogens in thoroughbred horses in the Hidaka district,
      Hokkaido, Japan.
AB  - A total of 87 Thoroughbred horses and 10 ixodid ticks from a ranch in Hidaka
      district, Hokkaido were tested for tick-borne diseases. Using the indirect
      fluorescent antibody (IFA) method, 3.4, 92.0 and 97.7% of the horses showed
      antibody titers of >= 80 against Anaplasma phagocytophilum, Rickettsia helvetica,
      and Borrelia garinii, respectively. This is the first report of infection with
      the 3 pathogens in horses in Japan. Using PCR, DNAs from the peripheral blood of
      all horses were found negative with any Anaplasma, Rickettsia and Borrelia spp.,
      while those from Haemaphysalis megaspinosa ticks were found positive for
      Anaplasma sp. closely related to A. phagocytophilum in Japan, and A. bovis. B.
      japonica was also detected in an H. flava tick for the first time.

PMID- 22878541
TI  - PCR-based detection of Leishmania donovani DNA in a stray dog from a visceral
      Leishmaniasis endemic focus in Bangladesh.
AB  - Although Phlebotomus argentipes as the only known vector of visceral
      leishmaniasis (VL) is zoophilic in nature, VL is considered to be anthroponotic
      in the Indian subcontinent. Peripheral blood samples from 85 stray dogs were
      examined for any molecular evidence of Leishmania infection in VL endemic areas
      of Bangladesh. Parasite DNA was detected in a blood sample from 1 of 85 (1.2%)
      stray dogs using ITS1-PCR, and PCR sequencing of the rRNA-ITS and cytochrome b
      gene confirmed that the parasitic DNA was Leishmania donovani. The results
      support the assumption that dogs are a probable animal reservoir for the
      Leishmania parasite in Bangladesh. It will be important to investigate the
      possible epidemiological role of dogs in domestic foci of VL endemic areas in
      Bangladesh.

PMID- 22878542
TI  - First molecular characterization of Anaplasma marginale in cattle and
      Rhipicephalus (Boophilus) microplus ticks in Cebu, Philippines.
AB  - Anaplasma marginale has been detected in the Philippines only by peripheral blood
      smear examination and serological methods. This study generally aimed to
      molecularly detect and characterize A. marginale in cattle and ticks in Cebu,
      Philippines. A total of 12 bovine blood samples and 60 Rhipicephalus (Boophilus)
      microplus ticks were collected on the Cebu Island in 2011. 16S rRNA-based
      screening-PCR and DNA sequencing revealed 8 cattle (66.7%) and 8 ticks (13.3%) to
      be positive for A. marginale, and 1 tick (1.7%) to be positive for A. centrale.
      Selected positive DNA samples were further characterized based on 16S rRNA
      (longer sequence), Msp5, Msp1alpha,gltA and groEL genes for phylogenetic
      analyses. Sequence identities of partial DNA fragments of A. marginale from the
      Philippines revealed 99.1-100% (16S rRNA, gltA, groEL and Msp5) and 94.3-97.6%
      (Msp1alpha) identities to the closest isolates from other countries. Moreover,
      sequence analysis of the Msp1alpha, gene showed 3 variants, including a case of
      co-infection with 2 variants. Phylogenetic analyses based on Msp1alpha and Msp5
      genes revealed that Philippine A. marginale isolates formed a monophyletic
      lineage, and were phylogenetically related to Brazilian and Chinese isolates. On
      the other hand, a highly specific and sensitive nested PCR based on groEL, with a
      detection limit of 2 copies/PCR, was developed to detect A. marginale in the
      Philippines. This study reported the first molecular detection and
      characterization of A. marginale in cattle and R. microplus in Cebu, Philippines.

PMID- 22878543
TI  - Quantitative PCR-based parasite burden estimation of Babesia gibsoni in the
      vector tick, Haemaphysalis longicornis (Acari: Ixodidae), fed on an
      experimentally infected dog.
AB  - Most causative agents of babesiosis, Babesia parasites, are transmitted
      transovarially in ixodid ticks. In this study, B. gibsoni, the causative agent of
      canine babesiosis which has transovarial transmission, was detected in tissues of
      the vector tick, Haemaphysalis longicornis using a modified quantitative PCR
      assay. Conventional PCR results showed that the newly designed primer set, which
      amplifies a 143-bp fragment of rhoptry-associated protein-1 (BgRAP-1) gene in B.
      gibsoni, was 100 times more sensitive than primers targeting P18 gene encoding 18
      kDa protein of B. gibsoni, which was recently renamed as thrombospondin related
      adhesive protein (BgTRAP) gene, in an artificially generated sample solution
      containing metagenomic DNA (B. gibsoni DNA extracted from infected dog blood
      mixed with tick DNA). The TaqMan probe-based quantitative PCR (qPCR) for BgRAP-1
      could also detect infected RBCs (iRBCs) at levels of 3.5 * 10(5) to 3.5 *
      10(1)/MUl, a range that is broader than that of a past SYBR Green-based qPCR
      method for P18/BgTRAP, which had a detection limit of 3.5 * 10(3) iRBCs/MUl.
      Using this qPCR assay, we attempted to quantify the B. gibsoni burden in tick
      ovaries and embryonated eggs. Levels of infection were normalized to the copy
      number of tick's genomic DNA fragment of ribosomal DNA internal transcribed
      spacer region 2 (ITS2) for the standardization. According to this, low levels of
      parasite burden were quantified in ovaries and eggs. This detection system is
      sensitive and is recommended as a tool for elucidating the biological
      interactions between the vector tick H. longicornis and the parasite, B. gibsoni.

PMID- 22878544
TI  - Isolation and partial characterization of Asian sea bass (Lates calcarifer)
      Vitellogenin.
AB  - A study was conducted to isolate, partial characterize Asian sea bass (Lates
      calcarifer) vitellogenin (vtg). Two-year-old juvenile L. calcarifer (n = 10) were
      given three intraperitoneal injections of 17-beta estradiol (E2) at a dose of 2
      mg/kg body weight to induce vitellogenesis. Blood was collected 3 days after the
      last injection, and plasma was purified through gel filtration chromatography. A
      broad single symmetrical peak consisting of vtg molecule was produced. Protein
      concentration was 0.059 mg/ml as determined by Bradfrod assay using bovine serum
      albumin as a standard. The protein appeared as one circulating form in Native
      PAGE considering the dimeric form of putative vtg with molecular weight of 545
      kDa. In SDS-PAGE under reducing conditions, two major bands appeared at 232.86
      and 118.80 kDa and minor bands at 100.60, 85.80 and 39.92 kDa, respectively. The
      purified vtg was used to generate a polyclonal antibody, and the specificity of
      antibody was assessed by Western blot analysis. Two major bands were
      immunoreacted, but no cross-reactivity was observed with plasma from non-induced
      males. The protein was characterized as phosphoglycolipoprotein as it positively
      stained for the presence of lipid, phosphorus and carbohydrate using Sudan Black
      B, methyl green and periodic acid/Schiff reagent solution, respectively. The
      amino acid composition was analyzed by high sensitivity amino acid analysis that
      showed high percentage of non-polar amino acids (~48 %). The results suggest the
      potential utilization of vtg as a basis tool to further study about reproductive
      physiology of this important economical species.

PMID- 22878545
TI  - [CT surveillance for primary site recurrence of squamous cell carcinoma of the
      head and neck].

PMID- 22878546
TI  - Testicular radiation dose after multimodal curative therapy for locally advanced
      rectal cancer. Influence on hormone levels, quality of life, and sexual
      functioning.
AB  - PURPOSE: The purpose of the current work was to prospectively measure the
      influence of testicular radiation dose on hormone levels, quality of life (QoL),
      and sexual functioning following multimodal therapy (neoadjuvant
      radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer.
      PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were
      treated at the University of Goettingen with radiochemotherapy (RCT) for locally
      advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two
      cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation
      doses were analyzed and correlated with hormone levels [luteinizing hormone (LH),
      follicle stimulating hormone (FSH), total testosterone and free androgen index
      (FAI) serum levels], QoL, and sexual functioning, which were determined before
      and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range
      0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous
      line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio,
      and the FAI/LH ratio were significantly decreased (3.5-3.0 ug/l, 0.9-0.4, 7.9
      4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased.
      QoL and sexual functioning were significantly impaired. However, there was no
      statistical correlation between testicular radiation dose and changes in hormone
      levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal
      cancer including RCT leads to hormone level changes and to impaired QoL and
      sexual functioning. However, because there was no apparent correlation between
      the analyzed parameters, QoL is probably also influenced by other factors, e.g.,
      psychosocial aspects.

PMID- 22878547
TI  - Long-term outcome after neoadjuvant radiochemotherapy in locally advanced
      noninflammatory breast cancer and predictive factors for a pathologic complete
      remission : results of a multivariate analysis.
AB  - BACKGROUND: An earlier published series of neoadjuvant radiochemotherapy (NRT
      CHX) in locally advanced noninflammatory breast cancer (LABC) has now been
      updated with a follow-up of more than 15 years. Long-term outcome data and
      predictive factors for pathologic complete response (pCR) were analyzed. PATIENTS
      AND METHODS: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated
      with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation
      therapy (EBRT) of 50 Gy (5 * 2 Gy/week) to the breast and the supra
      /infraclavicular lymph nodes combined with an electron boost in 214 cases
      afterwards or-in case of breast conservation-a 10-Gy interstitial boost with
      (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in
      192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The
      update of all follow-up ended in November 2011. Age, tumor grade, nodal status,
      hormone receptor status, simultaneous vs. sequential CHX, and the time interval
      between end of RT and surgery were examined in multivariate terms with pCR and
      overall survival as end point. RESULTS: The total pCR rate after neoadjuvant RT
      CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of
      cases. In initially node-positive cases (cN+), a complete nodal response (pN0)
      after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed
      that a longer time interval to surgery increased the probability for a pCR (HR
      1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a
      significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was
      obtained. Importantly, pCR was the strongest prognostic factor for long-term
      survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). CONCLUSION: pCR identifies
      patients with a significantly better prognosis for long-term survival. However, a
      long time interval to surgery (> 2 months) increases the probability of pCR after
      NRT-CHX.

PMID- 22878550
TI  - Motor cortex stimulation for Parkinson's disease: a modelling study.
AB  - Chronic motor cortex stimulation (MCS) is currently being investigated as a
      treatment method for Parkinson's disease (PD). Unfortunately, the underlying
      mechanisms of this treatment are unclear and there are many uncertainties
      regarding the most effective stimulation parameters and electrode configuration.
      In this paper, we present a MCS model with a 3D representation of several axonal
      populations. The model predicts that the activation of either the basket cell or
      pyramidal tract (PT) type axons is involved in the clinical effect of MCS. We
      propose stimulation protocols selectively targeting one of these two axon types.
      To selectively target the basket cell axons, our simulations suggest using either
      cathodal or bipolar stimulation with the electrode strip placed perpendicular
      rather than parallel to the gyrus. Furthermore, selectivity can be increased by
      using multiple cathodes. PT type axons can be selectively targeted with anodal
      stimulation using electrodes with large contact sizes. Placing the electrode
      epidurally is advisable over subdural placement. These selective protocols, when
      practically implemented, can be used to further test which axon type should be
      activated for clinically effective MCS and can subsequently be applied to
      optimize treatment. In conclusion, this paper increases insight into the neuronal
      population involved in the clinical effect of MCS on PD and proposes strategies
      to improve this therapy.

PMID- 22878551
TI  - The anabolic effect of perioperative nutrition depends on the patient's catabolic
      state before surgery.
AB  - OBJECTIVE: We tested the hypothesis that the anabolic effect of hypocaloric,
      isonitrogenous nutrition in patients undergoing colorectal surgery depends on the
      patient's preoperative catabolic state. BACKGROUND: Although there is evidence to
      suggest that total parenteral nutrition more effectively spares protein in
      depleted than in nondepleted cancer patients, the influence of preoperative
      catabolism on the anabolic effects of hypocaloric nutrition in patients
      undergoing elective surgery is unknown. METHODS: Seventeen patients undergoing
      colorectal surgery received intravenous infusion of glucose with amino acids.
      Feeding was administered over 72 hours, from 24 hours before until 48 hours after
      surgery. Glucose provided 50% of the patient's measured resting energy
      expenditure. Amino acids provided 20% of the resting energy expenditure. Whole
      body leucine balance (difference between the incorporation of leucine into
      protein = protein synthesis and endogenous leucine release = proteolysis) was
      determined using L-[1-(13)C]leucine kinetics before and 2 days after surgery. We
      analyzed the association between the postoperative increase in leucine balance
      and the following factors: preoperative leucine balance, protein breakdown,
      weight loss, oxygen consumption, circulating concentrations of glucose, free
      fatty acids, insulin, glucagon, cortisol, albumin, age, duration of surgery, and
      blood loss. RESULTS: Of 6 potentially relevant variables, 4 (weight loss, protein
      breakdown, albumin, and cortisol) were removed because they were not significant
      during the stepwise linear regression procedure. Leucine balance and age were the
      remaining 2 factors that remained with the final regression model: Deltaleucine
      balance = 19.1 - (0.20 * age [years]) - (0.58) * leucine balance(preOP)).
      CONCLUSIONS: We demonstrate a significant association between the degree of
      preoperative catabolism, the patient's age, and the anabolic effect of
      hypocaloric nutrition (ClinicalTrials.gov registration ID: NCT01414946).

PMID- 22878552
TI  - Stop and go: antagonistic signals in the specification of the Drosophila R7
      photoreceptor viewed from an evolutionary perspective.
AB  - The Drosophila R7 photoreceptor precursor is directed to its fate by signals from
      adjacent cells that activate its Receptor Tyrosine Kinase (RTK) and Notch (N)
      signaling pathways. Counter-intuitively, the N activity both promotes and
      inhibits the photoreceptor fate in the R7 precursor. We offer an evolutionary
      perspective for this in which earlier ommatidia had fewer photoreceptors and used
      N to inhibit the addition of any more. When additional photoreceptors were added
      by evolution, an RTK signal was used to overcome the N inhibition in these cells,
      and these new additions potently activated N in their neighboring cells,
      preventing them from also responding to the RTK signal. The R7 precursor also
      receives this block, and requires robust RTK activation for it to become a
      photoreceptor. This is achieved by N transcriptionally activating a new RTK, one
      that is potently activated in the R7 precursor and sufficing to overcome the N
      inhibition. The unusually high RTK signal in R7 requires additional transduction
      components not needed when the signal is mild; in R7 the small GTPases Ras and
      Rap are both required to transduce the signal, but in other photoreceptors Ras
      alone suffices.

PMID- 22878553
TI  - High levels of genetic variation within Helicoverpa armigera nucleopolyhedrovirus
      populations in individual host insects.
AB  - It has been well documented that baculovirus populations exhibit high levels of
      genetic variation. Due to the lack of sensitivity of the techniques currently
      used to study baculovirus genetic variation, relatively little is known about
      baculovirus genetic diversity at the individual insect level. Since denaturing
      gradient gel electrophoresis (DGGE) has key advantages over other methods used to
      study genetic variation in baculoviruses, DGGE assays were used to obtain a
      better understanding of the genetic variation within baculovirus populations in
      individual host insects. Helicoverpa armigera nucleopolyhedrovirus (HearNPV) was
      used as a model baculovirus system, and neonate H. armigera larvae were infected
      with one of two geographically distinct HearNPV isolates. DGGE assays for two
      lepidopteran-specific baculovirus genes, me53 and dbp1, detected many HearNPV
      genetic variants within individual host larvae, with up to 20 genetic variants
      detected in a 434-bp fragment of the dbp1 gene in a single neonate larva. High
      levels of HearNPV genetic diversity were detected in individual host larvae
      irrespective of the HearNPV isolate used to infect the larvae. This study sets a
      benchmark for HearNPV genetic variation in individual H. armigera larvae. The
      levels of HearNPV genetic diversity detected are higher than reported previously
      for a baculovirus population at the individual insect level.

PMID- 22878554
TI  - Pseudomonas linyingensis sp. nov.: a novel bacterium isolated from wheat soil
      subjected to long-term herbicides application.
AB  - A strain of genus Pseudomonas, LYBRD3-7(T) was isolated from long-term
      sulfonylurea herbicides applied wheat-field soil in Linying located in Henan
      province of China. This strain is a strictly aerobic and Gram-negative short rod
      shaped bacterium with single flagellum. Phylogenetic evaluation based on 16S rRNA
      gene sequence analysis placed this isolate as a member of Pseudomonas, and most
      closely to Pseudomonas tuomuerensis CGMCC 1.1365(T) (97.1 %) and P. alcaligenes
      IAM12411(T) (97.1 %). Morphological characters and chemotaxonomic data confirmed
      the affiliation of strain LYBRD3-7(T) to the genus Pseudomonas. The results of
      phylogenetic analysis, physiological and biochemical studies, and DNA-DNA
      hybridization allowed the differentiation of genotype and phenotype between
      strain LYBRD3-7(T) and the phylogenetic closest species with valid names. The
      name proposed for the new species is Pseudomonas linyingensis sp. nov. The type
      strain is LYBRD3-7(T) (=CGMCC 1.10701(T ) =LMG 25967(T)).

PMID- 22878555
TI  - PA2800 plays an important role in both antibiotic susceptibility and virulence in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an important human pathogen which causes a variety of
      infections. P. aeruginosa infections are often difficult to treat due to the
      pathogen's resistance to many antibiotics. Previously, it has been reported that
      a transposon insertion mutant in gene PA2800 of P. aeruginosa PAO1 was more
      sensitive to tetracycline and ciprofloxacin. Further characterization of this
      gene, a vacJ homolog, in this study indicated that this gene plays an important
      role in both antibiotic susceptibility and virulence in P. aeruginosa. The role
      of PA2800 in antibiotic susceptibility probably signifies its involvement in
      maintaining outer membrane stability, similar to the role of vacJ in E. coli and
      Shigella flexneri. However, in contrast to vacJ in other bacteria, PA2800 also
      affects antibiotic susceptibility by affecting the expression of oprH in P.
      aeruginosa. As shown by in vivo studies using a Drosophila melanogaster infection
      model, significantly increased virulence was observed in the PA2800 mutant when
      compared to the wild type, and such a difference is likely a result of disrupted
      outer membrane stability and altered expression of znuA in the mutant. The role
      of PA2800 or vacJ in antibiotic susceptibility and pathogenicity seems to be
      unique in P. aeruginosa in which it affects both outer membrane stability as well
      as gene expression.

PMID- 22878556
TI  - The gut bacteria associated with Camponotus japonicus Mayr with culture-dependent
      and DGGE methods.
AB  - The bacterial composition and distribution in the different gut regions of
      Camponotus japonicus were investigated using both culture-dependent method and
      culture-independent method of polymerase chain reaction and denaturing gradient
      gel electrophoresis (PCR-DGGE). Five different bacterial strains were isolated
      using culture-dependent method, and they all belong to the phylum Firmicutes,
      including three genera of bacteria Bacillus, Paenibacillus, and Enterococcus.
      Bacillus cereus and Enterococcus mundtii were found in the midgut; Paenibacillus
      sp. was isolated from the hindgut; and the other two Bacillus spp. were isolated
      from the crop. Twelve distinct DGGE bands were found using PCR-DGGE method, and
      their sequences blasting analysis shows that they are members of the
      Proteobacteria and the Firmicutes, respectively, including three genera
      (Pseudomonas, Candidatus Blochmannia, Fructobacillus) and one uncultured
      bacterium, in which Pseudomonas was the most dominant bacteria group in all the
      three gut regions. According to the DGGE profile, the three gut regions had very
      similar gut communities, and all the DGGE bands were presented in the midgut and
      hindgut, while just two bands representing Blochmannia were not present in the
      crop. The results of our study indicate that the gut of C. japonicus harbors
      several other bacteria besides the obligate endosymbionts Blochmannia, and more
      work should be carried on to verify if they are common in the guts of other
      Camponotus ants.

PMID- 22878557
TI  - Relation of child birth and breast-feeding burden with cadmium and tubular
      dysfunction marker levels in urine of adult women in non-polluted areas in Japan.
AB  - BACKGROUND AND OBJECTIVES: Cd absorption may be enhanced in association with iron
      (Fe) deficiency. Women have increased risks of Fe loss at the time of child birth
      as well as breast-feeding of children. Possible effects of these two factors were
      investigated in the present study. METHODS: Data were drawn from previous
      publications from this group on Cd and tubular dysfunction markers (i.e., alpha1
      microglobulin, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase) in urine
      of adult women in non-polluted areas in Japan. Information including age,
      smoking, number of children, and types of child feeding was obtained by self
      administered questionnaires at the time of urine sampling. In practice, 17,468
      cases were available, from which 12,869 cases were employed in the present
      analyses after exclusion of smokers, former or current patients of anemia or
      hypertension, and those with incomplete answers. Lactation burden was scored
      after coding of breast, mixed, and bottle feeding with 2, 1, and 0 for each child
      followed by summation for all children born to a mother. In order to exclude
      possible effect of aging, women were stratified by 5 years of age to randomly
      select equal numbers of cases and controls, followed by summation for all ages
      for comparison. RESULTS: The arithmetic mean age and the geometric mean Cd (as
      observed) were 49.7 years and 1.13 MUg/l urine. The number of children was 0-7,
      and lactation burden score ranged from 0-12. Multiple regression analyses were
      conducted with age and either number of children or lactation burden scores as
      independent variables and Cd as a dependent variable. The results showed that age
      was an influential variable. Comparison after matching for age showed that having
      1, 2, or 3 children or lactation burden score up to 2 were associated with a
      significant increase in Cd. Lactation burden score up to 2 was also associated
      with increased Cd in urine and such trend persisted up to the highest score of 5
      12. The results of trend tests were generally in agreement with these
      observations. Further comparison after age-matching showed that women having 2 or
      3 children but no lactation burden had higher Cd than those with no children. In
      contrast, Cd was not higher for those having 2 or 3 children with substantial
      lactation scores (i.e., 2-4 or 3-6) than for those with the same number of
      children without lactation burden. CONCLUSIONS: Giving birth to 1-3 children was
      associated with an increase in urinary Cd, suggesting that child birth might be
      associated with elevation in Cd body burden. The effect of lactation is probably
      attributable to that of number of children. Further studies are necessary to
      examine whether the association is also observable in mothers who have 3 or more
      children.

PMID- 22878558
TI  - Perceived physical exertion during healthcare work and risk of chronic pain in
      different body regions: prospective cohort study.
AB  - PURPOSE: To estimate the risk of developing chronic musculoskeletal pain in
      different body regions from varying degrees of perceived physical exertion during
      healthcare work. METHODS: Prospective cohort study among 4,977 Danish female
      healthcare workers responding to a baseline and follow-up questionnaire in 2005
      and 2006, respectively. Using multi-adjusted logistic regression analysis, the
      risk of developing chronic pain (>30 days last year) at follow-up in the low
      back, neck/shoulder, and knees-among those without pain (0 days last year) in
      these respective body regions at baseline-from moderate and strenuous (reference:
      light) perceived physical exertion during healthcare work was modeled. RESULTS:
      Adjusted for age, BMI, tenure, smoking status, and leisure physical activity,
      strenuous perceived physical exertion during healthcare work increased the risk
      of chronic low back pain (OR 3.16, 95 % CI 1.79-5.57) and chronic knee pain (OR
      1.87, 95 % CI 1.19-2.94) at follow-up among those without pain in these
      respective body regions at baseline. With additional adjustment for psychosocial
      work conditions, only the risk of developing chronic low back pain from strenuous
      physical exertion remained significant (OR 1.99, 95 % CI 1.02-3.88). Strenuous
      physical exertion was not a risk factor for chronic neck pain, and moderate
      physical exertion was not a risk factor for chronic pain in any of the body
      regions. CONCLUSION: Strenuous perceived physical exertion during healthcare work
      is a risk factor especially for developing chronic pain in the low back. The
      possible preventive effect of reducing strenuous physical exertion should be
      tested in randomized controlled trials.

PMID- 22878559
TI  - Mutual influence of backbone proline substitution and lipophilic tail character
      on the biological activity of simplified analogues of caspofungin.
AB  - The echinocandins represent the most recent class of antifungal drugs. Previous
      structure-activity relationship studies on these lipopeptides have relied mainly
      upon semisynthetic derivatives due to their complex chemical structures. A
      successful strategy for the rapid enantioselective synthesis of the branched
      fatty acid chain of caspofungin and analogues was developed to synthesize several
      simplified analogues of caspofungin. The specific minimum inhibitory activity of
      each mimic was determined against a panel of Candida strains. This approach gave
      access to new fully synthetic derived caspofungin mimics with high and selective
      antifungal activities against Candida strains. In addition, the data suggested an
      important role of the hydroxy proline residue in the bioactive conformation of
      the macrocyclic peptide ring structure.

PMID- 22878560
TI  - Ototoxicity in preterm infants: effects of genetics, aminoglycosides, and loud
      environmental noise.
AB  - Majority of hearing-loss cases with extremely preterm infants have no known
      etiology. There is a growing concern that the administration of aminoglycoside
      treatment in the noisy environment of the Neonatal Intensive Care Unit (NICU) may
      lead to hair-cell damage and subsequent auditory impairments. In addition,
      several mitochondrial DNA mutations are known to have been associated with
      aminoglycoside-induced hearing loss. This review provides a systematic analysis
      of the research in this area and elucidates the multifactorial mechanisms behind
      how mitochondrial DNA mutations, aminoglycosides and loud noise can potentiate
      ototoxicity in extremely preterm neonates. Recommended steps to minimize the risk
      of ototoxicity and improve clinical care for NICU infants are discussed.

PMID- 22878562
TI  - Variability in costs associated with total hip and knee replacement implants.
AB  - BACKGROUND: Implant costs associated with total hip replacement and total knee
      replacement procedures account for a large share of total costs and
      reimbursements to hospitals. Federal policymakers are promoting episode-of-care
      payment and other value-based delivery and payment reforms in part to encourage
      physicians and hospitals to cooperate in managing costs for these and other
      procedures. The present study quantifies the patient, hospital, and market
      characteristics associated with variation in implant and total procedure costs
      for hip and knee arthroplasty. METHODS: Clinical, demographic, and economic data
      were collected on 10,155 unilateral primary total knee replacement procedures and
      5013 unilateral primary total hip replacement procedures from sixty-one hospitals
      in 2008. Variation in implant costs per procedure was measured within and across
      hospitals. Multivariate statistical analyses were used to measure the association
      between patient and hospital characteristics and implant costs and total
      procedure costs. RESULTS: The average implant cost per case ranged from $1797 to
      $12,093 for total knee replacement procedures and from $2392 to $12,651 for total
      hip replacement procedures. For total knee replacement, 2.5% of total variation
      in device costs was attributable to patient characteristics and 61.0% was
      attributable to hospital characteristics; the remaining 36.5% of variance was
      attributable to within-hospital variation not due to patient or hospital
      characteristics. For total hip replacement, 4.4% of variance was attributed to
      patient characteristics, 36.1% was attributed to hospital characteristics, and
      59.5% was attributed to within-hospital variation not due to patient or hospital
      characteristics. CONCLUSIONS: There are substantial variations in total hip
      replacement and total knee replacement implant costs within and across hospitals
      after controlling for patient diagnoses and comorbidities. This variation is
      responsible for the majority of variation in the overall cost of total hip and
      knee replacement surgery.

PMID- 22878561
TI  - Herbal, vitamin, and mineral supplement use in patients enrolled in a cardiac
      rehabilitation program.
AB  - PURPOSE: The use of complementary and alternative medicine is common and
      continues to rise each year, both in the general population and among those with
      cardiovascular disease. While some supplements may incur risk, particularly when
      used concomitantly with cardiovascular medications, others have proven benefits.
      However, supplements such as antioxidants and many herbs can have significant
      interactions with cardiovascular medications. This study aimed to identify the
      percentage of patients enrolled in a cardiac rehabilitation program taking
      herbal, vitamin, and mineral supplements. METHODS: Electronic and paper charts of
      235 patients enrolled in a phase 3 cardiac rehabilitation program were reviewed.
      Their demographics, medical history, and medications were stratified in an Excel
      chart, using a large matrix from which data were imported into Matlab for
      analysis. Custom Matlab programs were created and compiled to determine variables
      of interest, including percentages of patients with a specific medical condition
      taking certain supplements. RESULTS: Sixty-seven percent of patients enrolled in
      the cardiac rehabilitation program were taking vitamins, with or without minerals
      (67%, 158 of 235). Multivitamin is the most common form of supplement (51%, 119
      of 235), followed by fish oil/omega-3 polyunsaturated fatty acids (27%, 64 of
      235). CONCLUSION: The majority of patients in a phase 3 cardiac rehabilitation
      program are taking some form of herbal, vitamin, or mineral supplement. Given
      frequent, complicated patient medication regimens, it is important to educate
      patients on the potential benefits as well as lack of evidence and possible
      dangers of supplements.

PMID- 22878563
TI  - Hypoxic preconditioning up-regulates DJ-1 protein expression in rat heart-derived
      H9c2 cells through the activation of extracellular-regulated kinase 1/2 pathway.
AB  - Myocardial preconditioning is a powerful phenomenon that can attenuate
      ischemia/reperfusion-induced oxidant stress and elicit delayed cardioprotection.
      Its mechanisms involve activation of intracellular signaling pathways and up
      regulation of the protective antioxidant proteins. DJ-1 protein, as a
      multifunctional intracellular protein, plays an important role in attenuating
      oxidant stress and promoting cell survival. In the present study, we investigated
      whether DJ-1 is up-regulated during the late phase of hypoxic preconditioning
      (HP) and the up-regulation of DJ-1 is mediated by extracellular-regulated kinase
      1/2 (ERK1/2) signaling pathway. Rat heart-derived H9c2 cells were exposed to HP.
      Twenty-four hours later cells were subjected to hypoxia/reoxygenation (H/R) and
      then cell viability, lactate dehydrogenase (LDH), intracellular reactive oxygen
      species (ROS), ERK1/2 phosphorylation, and DJ-1 protein were measured
      appropriately. The results showed that HP efficiently attenuated H/R-induced
      viability loss and LDH leakage. In addition, HP promoted ERK1/2 activation, up
      regulated DJ-1 protein expression, inhibited H/R induced the elevation of ROS.
      However, when ERK1/2 phosphorylation was specifically inhibited by U0126, the
      increase in DJ-1 expression occurring during HP was almost completely abolished
      and, as a result, the delayed cardioprotection induced by HP was abolished, and
      the inhibitory effect of HP on H/R-induced oxidant stress was also reversed.
      Furthermore, knocking down DJ-1 by siRNA attenuated the delayed cardioprotection
      induced by HP. Our data indicate that HP can up-regulate DJ-1 protein expression
      through the ERK1/2-dependent signaling pathway. Importantly, DJ-1 might be
      involved in the delayed cardioprotective effect of HP against H/R injury.

PMID- 22878565
TI  - Computerized assessment of pedophilic sexual interest through self-report and
      viewing time: reliability, validity, and classification accuracy of the affinity
      program.
AB  - Affinity is a computerized assessment tool that combines viewing time and self
      report measures of sexual interest. The present study was designed to assess the
      diagnostic properties of Affinity with respect to sexual interest in prepubescent
      children. Reliability of both self-report and viewing time components was
      estimated to be high. The group profile of a sample of pedophilic adult male
      child molesters (n = 42, all of whom admitted their offenses) differed from the
      group profiles of male community controls (n = 95) and male nonsexual offenders
      (n = 27), respectively. More specifically, both ratings and viewing times for
      images showing small children or prejuvenile children were significantly higher
      within the child molester sample than in either of the other two groups,
      attesting to the validity of the measures. Overall classification accuracy,
      however, was mediocre: A multivariate classification routine yielded 50%
      sensitivity for child molester status at the cost of 13% false positives. The
      implications for forensic use of Affinity are discussed.

PMID- 22878566
TI  - [Kampo pharmacology: Kampo medicines as a complementary and alternative medicine
      (CAM)].

PMID- 22878567
TI  - [Vascular pharmacology of Kampo medicine for Mibyou (disease-oriented states)].

PMID- 22878568
TI  - [Chinese herbal medicines to inhibit the replication of influenza viruses].

PMID- 22878564
TI  - Characterization of hsp27 kinases activated by elevated aortic pressure in heart.
AB  - Chronic hemodynamic overload results in left ventricular hypertrophy, fibroblast
      proliferation, and interstitial fibrosis. The small heat shock protein hsp27 has
      been shown to be cardioprotective and this requires a phosphorylatable form of
      this protein. To further understand the regulation of hsp27 in heart in response
      to stress, we investigated the ability of elevated aortic pressure to activate
      hsp27-kinase activities. Isolated hearts were subjected to retrograde perfusion
      and then snap frozen. Hsp27-kinase activity was measured in vitro as hsp27
      phosphorylation. Immune complex assays revealed that MK2 activity was low in non
      perfused hearts and increased following crystalline perfusion at 60 or 120 mmHg.
      Hsp27-kinase activities were further studied following ion-exchange
      chromatography. Anion exchange chromatography on Mono Q revealed 2 peaks (b and
      c) of hsp27-kinase activity. A third peak a was detected upon chromatography of
      the Mono Q flow-through fractions on the cation exchange resin, Mono S. The hsp27
      kinase activity underlying peaks a and c increased as perfusion pressure was
      increased from 40 to 120 mmHg. In contrast, peak b increased over pressures 60
      100 mmHg but was decreased at 120 mmHg. Peaks a, b, and c contained MK2
      immunoreactivity, whereas MK3 and MK5 immunoreactivity was detected in peak a.
      p38 MAPK and phospho-p38 MAPK were also detected in peaks b and c but absent from
      peak a. Hsp27-kinase activity in peaks b and c (120 mmHg) eluted from a Superose
      12 gel filtration column with an apparent molecular mass of 50 kDa. Hence, peaks
      b and c were not a result of MK2 forming complexes. In-gel hsp27-kinase assays
      revealed a single 49-kDa renaturable hsp27-kinase activity in peaks b and c at 60
      mmHg, whereas several hsp27-kinases (p43, p49, p54, p66) were detected in peaks b
      and c from hearts perfused at 120 mmHg. Thus, multiple hsp27-kinases were
      activated in response to elevated aortic pressure in isolated, perfused rat
      hearts and hence may be implicated in regulating the cardioprotective effects of
      hsp27 and thus may represent targets for cardioprotective therapy.

PMID- 22878569
TI  - [Pharmacological studies for the ameliorative effects of yokukansan on memory
      deficits and abnormal behavior in an animal model of dementia].

PMID- 22878570
TI  - [Approach to evidence-based aromatherapy: pharmacological effects of inhaled
      aromatic natural medicines].

PMID- 22878571
TI  - [Interactions between normal and transformed epithelial cells: their clinical
      applications].

PMID- 22878572
TI  - [GPSP: good post-marketing study practice].

PMID- 22878573
TI  - [Pharmacological and clinical profile of gabapentin enacarbil: a novel drug for
      the treatment of restless legs syndrome].

PMID- 22878574
TI  - [Adenocarcinoma of the esophagogastric junction: diagnostic and surgical
      strategies].

PMID- 22878575
TI  - [Endoscopic resection of early carcinoma of the gastroesophageal junction].
AB  - The endoscopic examination of the gastroesophageal junction focuses on
      confirmation of neoplastic lesions or precursors. Recent technical advances, such
      as high resolution video endoscopes and chromoendoscopy may improve the
      sensitivity of endoscopic diagnosis. Biopsies are still a necessary part of the
      examination, however, they may be not representative for the lesion and should be
      replaced by a complete endoscopic resection wherever possible. If the
      histopathological examination reveals a well differentiated carcinoma without
      microlymphatic and microvenous infiltration with tumor-free resection margins
      which is limited to the mucosa, endoscopic resection can be regarded as curative.
      While tumor infiltration depth and differentiation are determined by the tumor
      biology, complete resection can be achieved by a sophisticated endoscopic
      technique which requires vast experience and extensive equipment.

PMID- 22878576
TI  - [Modern diagnostics and stage-oriented surgery: therapy of adenocarcinoma of the
      esophagogastric junction].
AB  - The basis for decision-making about an individualized surgical treatment of
      adenocarcinoma of the esophagogastric junction is tumor staging and exact
      evaluation of the topography of the tumor in the small junctional area. The
      diagnostics mainly comprise endoscopy, biopsy, endosonography, computed
      tomography and partially diagnostic laparoscopy. This results in a clinical TNM
      staging and an evaluation according to the AEG classification from oral to aboral
      in type I (esophagus), type II (cardia) and type III (subcardia). Endoscopic
      resection is only appropriate for the infrequent mucosal carcinomas whereas the
      majority of the junctional carcinomas are treated by surgical resection. This is
      combined with neoadjuvant treatment in case of T3 or resectable T4 carcinomas. A
      type I carcinoma is removed by radical transthoracic en bloc esophagectomy with
      high intrathoracic esophagogastrostomy after gastric pull-up. In case of type II
      or III carcinomas, a transhiatal extended gastrectomy including distal esophageal
      resection is performed with reconstruction by Roux en Y esophagojejunostomy in
      the lower mediastinum. However, some advanced type II carcinomas which cannot be
      resected R0 at the esophagus need esophagectomy and gastric pull-up. This
      surgical strategy is justified by the topography of the lesion and the
      corresponding lymphatic drainage. Very rare indications are seen for a limited
      resection with interposition of small bowel in some mucosal carcinomas or total
      esophagogastrectomy with colon interposition in very advanced tumors. The
      neoadjuvant treatment comprises especially chemoradiation for type I and
      chemotherapy for type II and III carcinomas and leads to a significant survival
      benefit compared to surgery alone.

PMID- 22878578
TI  - [Completion thyroidectomy for differentiated thyroid cancer : effect of timing].

PMID- 22878577
TI  - [Emergency interventions for perforation and bleeding in esophageal cancer
      patients].
AB  - Bleeding and perforation in esophageal cancer patients are rare but associated
      with a high morbidity and mortality. Because of disappointing results after
      primary surgical exploration and resection endoscopic intervention was introduced
      as the primary treatment option with an improved outcome. Aortoesophageal and
      esophagobronchial fistulas may occur spontaneously or secondary to stenting of
      the esophagus. They are uncommon but fatal if untreated. The first option is
      prompt placement of a stent graft as a bridging solution followed by surgical
      treatment.

PMID- 22878579
TI  - [Laparoscopic distal pancreatectomy : is it superior to the open technique?].

PMID- 22878581
TI  - [Recruiting multicenter surgical studies in Germany].

PMID- 22878580
TI  - [Pathological complete response to neoadjuvant radiochemotherapy for rectal
      cancer : meta-analysis shows excellent long-term outcome].

PMID- 22878582
TI  - [Treatment of periprosthetic and peri-implant fractures : modern plate
      osteosynthesis procedures].
AB  - Periprosthetic fractures are increasing not only due to the demographic
      development with high life expectancy, the increase in osteoporosis and increased
      prosthesis implantation but also due to increased activity of the elderly
      population. The therapeutic algorithms are manifold but general valid rules for
      severe fractures are not available. The most commonly occurring periprosthetic
      fractures are proximal and distal femoral fractures but in the clinical routine
      fractures of the tibial head, ankle, shoulder, elbow and on the borders to other
      implants (peri-implant fractures) and complex interprosthetic fractures are being
      seen increasingly more. It is to be expected that in the mid-term further
      options, such as cement augmentation of cannulated polyaxial locking screws will
      extend the portfolio of implants for treatment of periprosthetic fractures. The
      aim of this review article is to present the new procedures for osteosynthesis of
      periprosthetic fractures.

PMID- 22878583
TI  - British Columbia interprofessional model for simulation-based education in health
      care: a network of simulation sites.
AB  - The rapid uptake of simulation-based education has led to the development of
      simulation programs and centers all around the world. Unfortunately, many of
      these centers are functioning as localized silos and not taking advantage of the
      potential for collaboration with other regional centers to promote
      interprofessional education. In the province of British Columbia (BC), Canada, 38
      institutions, including health care authorities, universities, colleges, and
      other health-related organizations, have participated in assessing the use of
      simulation in BC and in developing a provincial model that enables collaboration
      and interprofessional learning at the provincial level.This article describes
      methods and results of a needs assessment and discusses an interprofessional
      simulation in health care educational model that provides access for all health
      care professionals in BC regardless of their geographic location and/or
      institutional affiliation. We anticipate that this information will be useful to
      and supportive of others in developing simulation collaborations in their
      respective regions.

PMID- 22878584
TI  - Validation of virtual reality simulation for obstetric ultrasonography: a
      prospective cross-sectional study.
AB  - INTRODUCTION: Ultrasonography is an important skill for obstetricians and
      gynecologists; however, trainees have highlighted ultrasonography as an area of
      deficiency in their training. We undertook a prospective cross-sectional
      comparative study to assess content and construct validity of an ultrasound
      virtual reality (VR) simulator (UltraSim). METHODS: Twenty-six physicians and
      sonographers of varied ultrasonography experience were recruited and divided into
      trainees (no formal ultrasonography training) and expert (certified) categories.
      They performed a VR simulation crown-rump length (CRL) ultrasound scan and growth
      ultrasound scan measuring biparietal diameter, occipitofrontal diameter,
      abdominal anteroposterior and transverse diameters, and femur length. Maximum
      pool depth (MPD), placental site, and fetal presentation were also assessed.
      Outcome measures included the mean absolute deviation and the variance of the
      absolute deviation from true measurements. Accuracy of determining placental
      site, fetal presentation, and MPD was assessed. The time taken to perform each
      type of scan was recorded. RESULTS: Trainees had significantly greater variation
      of measurement of CRL (P = 0.025) than the expert group. For late-pregnancy fetal
      biometry, the absolute deviation and the degree of variability for all
      measurements differed. These differences were statistically significant (P <
      0.05) for all measurements except abdominal diameters and MPD. Trainees took
      significantly longer time to obtain CRL and fetal biometric scans (P < 0.001).
      All subjects correctly identified fetal presentation and placental site.
      CONCLUSIONS: Clinicians with differing ultrasonography expertise showed differing
      skill with the UltraSim VR simulator, demonstrating construct validity for skills
      needed in simulation. Consideration should be given to investigating whether
      trainees with minimal scanning experience can improve their clinical skills and
      efficiency with VR simulation.

PMID- 22878585
TI  - Preventing wrong-site invasive procedures outside the operating room:  a
      thoracentesis simulation case scenario.

PMID- 22878586
TI  - Does surgical "warming up" improve laparoscopic simulator performance?
AB  - INTRODUCTION: The objective of this study was to determine if preoperative
      warming up by obstetrics and gynecology trainees, using a validated bench model
      for intracorporeal suturing, improves efficiency, precision, and quality of
      laparoscopic suturing. METHODS: A randomized crossover design was used. Fourteen
      obstetrics and gynecology residents were randomized [3 junior (year 2) and 11
      senior (years 3-5) residents]. Participants were randomized to warm-up or no warm
      up and then acted as their own controls at least 2 weeks later. Warm-up consisted
      of the use of a laparoscopic bench model to practice intracorporeal suturing for
      15 minutes. All participants performed a prevalidated intracorporeal suturing
      task (after either warm-up or no warm-up), which was scored based on time,
      precision, and knot strength. Each participant also completed a questionnaire
      anonymously to determine if they believed that warming up improved their
      performance, regardless of the score they received. RESULTS: Thirteen
      participants completed the study. There was no difference in score when warm-up
      was compared with no warm-up for the group as a whole. When the junior residents
      were excluded from the analysis, however, analysis of variance showed a
      significant improvement in score only when a warm-up was completed in the second
      session (P = 0.022). The questionnaire revealed that 81.8% of participants felt
      that warming up subjectively improved their ability, independent of their actual
      score. CONCLUSIONS: This study demonstrates that a preoperative warm-up, combined
      with repetition, is beneficial in improving senior obstetrics and gynecology
      residents' laparoscopic suturing performance. This demonstrates a novel approach
      to resident education for teaching advanced laparoscopic skills.

PMID- 22878587
TI  - Biological responses to TGF-beta in the mammary epithelium show a complex
      dependency on Smad3 gene dosage with important implications for tumor
      progression.
AB  - TGF-beta plays a dual role in epithelial carcinogenesis with the potential to
      either suppress or promote tumor progression. We found that levels of Smad3 mRNA,
      a critical mediator of TGF-beta signaling, are reduced by approximately 60% in
      human breast cancer. We therefore used conditionally immortalized mammary
      epithelial cells (IMEC) of differing Smad3 genotypes to quantitatively address
      the Smad3 requirement for different biologic responses to TGF-beta. We found that
      a two-fold reduction in Smad3 gene dosage led to complex effects on TGF-beta
      responses; the growth-inhibitory response was retained, the pro-apoptotic
      response was lost, the migratory response was reduced, and the invasion response
      was enhanced. Loss of the pro-apoptotic response in the Smad3(+/-) IMECs
      correlated with loss of Smad3 binding to the Bcl-2 locus, whereas retention of
      the growth-inhibitory response in Smad3 IMECs correlated with retention of Smad3
      binding to the c-Myc locus. Addressing the integrated outcome of these changes in
      vivo, we showed that reduced Smad3 levels enhanced metastasis in two independent
      models of metastatic breast cancer. Our results suggest that different biologic
      responses to TGF-beta in the mammary epithelium are differentially affected by
      Smad3 dosage and that a mere two-fold reduction in Smad3 is sufficient to promote
      metastasis.

PMID- 22878589
TI  - Selection of independent components based on cortical mapping of electromagnetic
      activity.
AB  - Independent component analysis (ICA) has been widely used to attenuate
      interference caused by noise components from the electromagnetic recordings of
      brain activity. However, the scalp topographies and associated temporal waveforms
      provided by ICA may be insufficient to distinguish functional components from
      artifactual ones. In this work, we proposed two component selection methods, both
      of which first estimate the cortical distribution of the brain activity for each
      component, and then determine the functional components based on the parcellation
      of brain activity mapped onto the cortical surface. Among all independent
      components, the first method can identify the dominant components, which have
      strong activity in the selected dominant brain regions, whereas the second method
      can identify those inter-regional associating components, which have similar
      component spectra between a pair of regions. For a targeted region, its component
      spectrum enumerates the amplitudes of its parceled brain activity across all
      components. The selected functional components can be remixed to reconstruct the
      focused electromagnetic signals for further analysis, such as source estimation.
      Moreover, the inter-regional associating components can be used to estimate the
      functional brain network. The accuracy of the cortical activation estimation was
      evaluated on the data from simulation studies, whereas the usefulness and
      feasibility of the component selection methods were demonstrated on the
      magnetoencephalography data recorded from a gender discrimination study.

PMID- 22878588
TI  - S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human
      basal-like breast cancer.
AB  - Increased inducible nitric oxide synthase (NOS2) expression in breast tumors is
      associated with decreased survival of estrogen receptor negative (ER-) breast
      cancer patients. We recently communicated the preliminary observation that nitric
      oxide (NO) signaling results in epidermal growth factor receptor (EGFR) tyrosine
      phosphorylation. To further define the role of NO in the pathogenesis of ER-
      breast cancer, we examined the mechanism of NO-induced EGFR activation in human
      ER- breast cancer. NO was found to activate EGFR and Src by a mechanism that
      includes S-nitrosylation. NO, at physiologically relevant concentrations, induced
      an EGFR/Src-mediated activation of oncogenic signal transduction pathways
      (including c-Myc, Akt, and beta-catenin) and the loss of PP2A tumor suppressor
      activity. In addition, NO signaling increased cellular EMT, expression and
      activity of COX-2, and chemoresistance to adriamycin and paclitaxel. When
      connected into a network, these concerted events link NO to the development of a
      stem cell-like phenotype, resulting in the upregulation of CD44 and STAT3
      phosphorylation. Our observations are also consistent with the finding that NOS2
      is associated with a basal-like transcription pattern in human breast tumors.
      These results indicate that the inhibition of NOS2 activity or NO signaling
      networks may have beneficial effects in treating basal-like breast cancer
      patients.

PMID- 22878590
TI  - Cardiovascular responses and differential changes in mitogen-activated protein
      kinases following repeated episodes of binge drinking.
AB  - AIMS: Excessive alcohol use in the form of binge drinking is associated with many
      adverse medical outcomes. Using an animal model, the primary objective of this
      study was to determine the effects of repeated episodes of binge drinking on
      myocardial structure, blood pressure (BP) and activation of mitogen-activated
      protein kinases (MAPKs). The effects of carvedilol, a beta-adrenergic blocker,
      were also examined in this animal model of binge drinking. METHODS: Rats were
      randomized into three groups: control, binge and binge + carvedilol (20 mg/kg).
      Animals received intragastric administration of 5 g ethanol/kg in the morning * 4
      days (Monday-Thursday) followed by no ethanol on Friday-Sunday. Animals were
      maintained on the protocol for 5 weeks. BP was measured using radiotelemetry
      methods. Animals underwent echocardiography at baseline, 2.5 and 5 weeks.
      Myocardial MAPKs were analyzed at 5 weeks using western blot techniques. RESULTS:
      Over the course of 5 weeks, binge drinking was associated with significant
      transient increases in BP that were greater at 4 and 5 weeks compared with
      earlier time points. Carvedilol treatment significantly attenuated the binge
      induced transient increases in BP at 4 and 5 weeks. No significant changes were
      found in echocardiographic parameters at any time period; however, binge drinking
      was associated with increased phosphorylation of p38 MAPK, which was blocked by
      carvedilol treatment. CONCLUSION: Repeated episodes of binge drinking result in
      progressive and transient increases in BP, no change in myocardial structure and
      differential regulation of MAPK activation.

PMID- 22878591
TI  - Advanced gestational age increases serum carbohydrate-deficient transferrin
      levels in abstinent pregnant women.
AB  - AIMS: Carbohydrate-deficient transferrin (%CDT) is a well-established and highly
      specific biomarker for sustained heavy consumption of alcohol. However, in
      pregnant women, the specificity of this biomarker might be affected by advanced
      gestational age, even after accounting for increased transferrin concentrations
      in pregnancy. The goal of this prospective study was to assess the variability in
      %CDT during pregnancy among alcohol-abstaining patients. METHODS: Patients were
      recruited during one of the first prenatal care visits and followed-up to term.
      Abstinence was confirmed by maternal self-report and by alcohol biomarkers.
      Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase,
      urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol
      (PEth). In addition, PEth was measured in a dry blood spot card obtained from a
      newborn. For %CDT analysis, serum samples were collected at baseline and at term
      and analyzed by an internationally validated high-performance liquid
      chromatography and spectrophotometric detection method. RESULTS: At recruitment
      (mean gestational age 22.6 +/- 7.3 weeks), the mean %CDT concentration was 1.49
      +/- 0.30%, while at term, it increased to 1.67 +/- 0.28% (P = 0.001). Using a
      conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would
      be classified as 'positive' for this biomarker at recruitment and at term,
      respectively (P = 0.011 ). CONCLUSION: These results suggest that a conventional
      cutoff of 1.7% might be too low for pregnant women and would generate false
      positive results. We propose that %CDT >2.0% be used as a cutoff concentration
      indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this
      cutoff for heavy drinking during pregnancy needs to be assessed further.

PMID- 22878592
TI  - The high angiogenic activity in very early breast cancer enables reliable imaging
      with VEGFR2-targeted microbubbles (BR55).
AB  - OBJECTIVES: Tumour xenografts of well-discernible sizes can be examined well by
      molecular ultrasound. Here, we investigated whether very early breast carcinomas
      express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging
      with targeted microbubbles. METHODS: MCF-7 breast cancer xenografts were
      orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm(3) (2
      mm diameter) up to 65 mm(3) (5 mm diameter) were examined with automated 3D
      molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles
      (BR55). Additionally, the relative tumour blood volume was assessed with non
      targeted microbubbles (BR38). In vivo ultrasound data were validated by
      quantitative immunohistochemistry. RESULTS: Very small lesions 2 mm in diameter
      showed the highest binding of VEGFR2-specific microbubbles. In larger tumours
      significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2
      targeted microbubbles was still high enough for imaging. The relative blood
      volume was comparable at all tumour sizes. Both findings were confirmed by
      immunohistochemistry. Additionally, a significantly enhanced number of large and
      mature vessels were detected with increasing tumour size (p < 0.01), explaining
      the decrease in VEGFR2 expression during tumour growth. CONCLUSIONS: 3D molecular
      ultrasound using BR55 is very well suited to depicting the angiogenic activity in
      very small breast lesions, suggesting its potential for detecting and
      characterising these lesions.

PMID- 22878593
TI  - Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells
      and a target for antibody-dependent cell-mediated cytotoxicity.
AB  - Protein glycosylation often changes during cancer development, resulting in the
      expression of cancer-associated carbohydrate antigens. In particular mucins such
      as MUC1 are subject to these changes. We previously identified an immunodominant
      Tn-MUC1 (GalNAc-alpha-MUC1) cancer-specific epitope not covered by immunological
      tolerance in MUC1 humanized mice and man. The objective of this study was to
      determine if mouse antibodies to this Tn-MUC1 epitope induce antibody-dependent
      cellular cytotoxicity (ADCC) pivotal for their potential use in cancer
      immunotherapy. Binding affinity of mAb 5E5 directed to Tn-MUC1 was investigated
      using BiaCore. The availability of Tn-MUC1 on the surface of breast cancer cells
      was evaluated by immunohistochemistry, confocal microscopy, and flow cytometry,
      followed by in vitro assessment of antibody-dependent cellular cytotoxicity by
      mAb 5E5. Biacore analysis demonstrated high affinity binding (KD = 1.7 nM) of mAb
      5E5 to its target, Tn-MUC1. Immunolabelling with mAb 5E5 revealed surface
      expression of the Tn-MUC1 epitope in breast cancer tissue and cell lines, and mAb
      5E5 induced ADCC in two human breast cancer cell lines, MCF7 and T47D. Aberrantly
      glycosylated MUC1 is expressed on the surface of breast cancer cells and a target
      for antibody-dependent cell-mediated cytotoxicity suggesting that antibodies
      targeting glycopeptide epitopes on mucins are strong candidates for cancer
      specific immunotherapies.

PMID- 22878594
TI  - Facile coupling of propargylic, allylic and benzylic alcohols with allylsilane
      and alkynylsilane, and their deoxygenation with Et3SiH, catalyzed by Bi(OTf)3 in
      [BMIM][BF4] ionic liquid (IL), with recycling and reuse of the IL.
AB  - Allyltrimethylsilane (allyl-TMS) reacts with propargylic alcohols 1a-1d in the
      presence of 10% Bi(OTf)(3) in [BMIM][BF(4)] solvent to furnish the corresponding
      1,5-enynes in respectable isolated yields (87-93%) at room temperature. The
      utility of Bi(OTf)(3) as a superior catalyst was demonstrated in a survey study
      on coupling of allyl-TMS with employing several metallic triflates (Bi, Ln, Al,
      Yb) as well as, B(C(6)F(5))(3), Zn(NTf(2))(2) and Bi(NO(3))(3).5H(2)O. Coupling
      of cyclopropyl substituted propargylic alcohol with allyl-TMS gave the skeletally
      intact 1,5-enyne and a ring opened derivative as a mixture. Coupling of
      propargylic/allylic alcohol with allyl-TMS resulted in allylation at both
      benzylic (2 isomers) and propargylic positions, as major and minor products
      respectively. The scope of this methodology for allylation of a series of allylic
      and benzylic alcohols was explored. Chemoselective reduction of a host of
      propargylic, propagylic/allylic, bis-allylic, allylic, and benzylic alcohols with
      Et(3)SiH was achieved in high yields with short reaction times. The same approach
      was successfully applied to couple representative propargylic and allylic
      alcohols with 1-phenyl-2-trimethylsilylacetylene. The recovery and reuse of the
      ionic liquid (IL) was gauged in a case study with minimal decrease in isolated
      yields after six cycles.

PMID- 22878596
TI  - Blended learning in surgery using the Inmedea Simulator.
AB  - BACKGROUND: Recently, medical education in surgery has experienced several
      modifications. We have implemented a blended learning module in our teaching
      curriculum to evaluate its effectiveness, applicability, and acceptance in
      surgical education. METHODS: In this prospective study, the traditional face-to
      face learning of our teaching curriculum for fourth-year medical students (n =
      116) was augmented by the Inmedea Simulator, a web-based E-learning system, with
      six virtual patient cases. Student results were documented by the system and
      learning success was determined by comparing patient cases with comparable
      diseases (second and sixth case). The acceptance among the students was evaluated
      with a questionnaire. RESULTS: After using the Inmedea Simulator, correct
      diagnoses were found significantly (P < 0.05) more often, while an incomplete
      diagnostic was seen significantly (P < 0.05) less often. Significant overall
      improvement (P < 0.05) was seen in sixth case (62.3 +/- 5.6 %) vs. second case
      (53.9 +/- 5.6 %). The questionnaire revealed that our students enjoyed the
      surgical seminar (score 2.1 +/- 1.5) and preferred blended learning (score 2.5 +/
      1.2) to conventional teaching. CONCLUSION: The blended learning approach using
      the Inmedea Simulator was highly appreciated by our medical students and resulted
      in a significant learning success. Blended learning appears to be a suitable tool
      to complement traditional teaching in surgery.

PMID- 22878597
TI  - Qualitative and quantitative variations in withanolides and expression of some
      pathway genes during different stages of morphogenesis in Withania somnifera
      Dunal.
AB  - Withania somnifera Dunal is an important and extensively studied medicinal plant;
      however, there is no report available that relates withanolide content and its
      profile in relation to the expression of pathway genes during different
      morphogenic stages. In this study, withanolide A, withaferin A, and withanone,
      the major withanolides of W. somnifera, were measured in different in vitro
      stages during organogenesis, viz., shoot to root (direct rhizogenesis)/root to
      shoot (indirect via callus phase) transition vis-a-vis expression levels of key
      pathway genes involved in withanolide biosynthetic pathways. The morphogenic
      transitions were found to be tightly linked to the pattern of accumulation of
      withanolides. The high expression levels of most of the pathway genes in in vitro
      shoots in comparison to in vitro root and callus tissues exhibited a direct co
      relation with the maximum withanolide content (>2.7 mg/gDW). The biogenesis of
      withaferin A, a major constituent of the leaves, was however found to be tightly
      linked to shoots/green tissue. In addition, we were also able to establish an
      efficient regeneration system from roots for their further utilization in
      biotechnological applications.

PMID- 22878595
TI  - Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory
      diseases.
AB  - Autophagy is now emerging as a spotlight in trafficking events that activate
      innate and adaptive immunity. It facilitates innate pathogen detection and
      antigen presentation, as well as pathogen clearance and lymphocyte homeostasis.
      In this review, we first summarize new insights into its functions in immunity,
      which underlie its associations with autoimmunity. As some lines of evidence are
      emerging to support its role in autoimmune and autoinflammatory diseases, we
      further discuss whether and how it affects autoimmune diseases including systemic
      lupus erythematosus, rheumatoid arthritis, diabetes mellitus and multiple
      sclerosis, as well as autoinflammatory diseases, such as Crohn disease and
      vitiligo.

PMID- 22878598
TI  - An improved Agrobacterium-mediated transformation of recalcitrant indica rice
      (Oryza sativa L.) cultivars.
AB  - Agrobacterium-mediated transformation of indica rice varieties has been quite
      difficult as these are recalcitrant to in vitro responses. In the present study,
      we established a high-efficiency Agrobacterium tumefaciens-mediated
      transformation system of rice (Oryza sativa L. ssp. indica) cv. IR-64, Lalat, and
      IET-4786. Agrobacterium strain EHA-101 harboring binary vector pIG121-Hm,
      containing a gene encoding for beta-glucuronidase (GUS) and hygromycin
      resistance, was used in the transformation experiments. Manipulation of different
      concentrations of acetosyringone, days of co-culture period, bacterial suspension
      of different optical densities (ODs), and the concentrations of L-cysteine in
      liquid followed by solid co-culture medium was done for establishing the
      protocol. Among the different co-culture periods, 5 days of co-culture with
      bacterial cells (OD600 nm = 0.5-0.8) promoted the highest frequency of
      transformation (83.04 %) in medium containing L-cysteine (400 mg l(-1)). Putative
      transformed plants were analyzed for the presence of a transgene through genomic
      PCR and GUS histochemical analyses. Our results also suggest that different
      cultural conditions and the addition of L-cysteine in the co-culture medium
      improve the Agrobacterium-mediated transformation frequencies from an average of
      12.82 % to 33.33 % in different indica rice cultivars.

PMID- 22878599
TI  - The effect of iliac crest autograft on the outcome of fusion in the setting of
      degenerative spondylolisthesis: a subgroup analysis of the Spine Patient Outcomes
      Research Trial (SPORT).
AB  - BACKGROUND: There is considerable controversy about the long-term morbidity
      associated with the use of posterior autologous iliac crest bone graft for lumbar
      spine fusion procedures compared with the use of bone-graft substitutes. The
      hypothesis of this study was that there is no long-term difference in outcome for
      patients who had posterior lumbar fusion with or without iliac crest autograft.
      METHODS: The study population includes patients enrolled in the degenerative
      spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who
      underwent lumbar spinal fusion. Patients were divided according to whether they
      had or had not received posterior autologous iliac crest bone graft. RESULTS:
      There were 108 patients who had fusion with iliac crest autograft and 246 who had
      fusion without iliac crest autograft. There were no baseline differences between
      groups in demographic characteristics, comorbidities, or baseline clinical
      scores. At baseline, the group that received iliac crest bone graft had an
      increased percentage of patients who had multilevel fusions (32% versus 21%;
      p=0.033) and L5-S1 surgery (37% versus 26%; p=0.031) compared with the group
      without iliac crest autograft. Operative time was higher in the iliac crest bone
      graft group (233.4 versus 200.9 minutes; p<0.001), and there was a trend toward
      increased blood loss (686.9 versus 582.3; p=0.057). There were no significant
      differences in postoperative complications, including infection or reoperation
      rates, between the groups. On the basis of the numbers available, no significant
      differences were detected between the groups treated with or without iliac crest
      bone graft with regard to the scores on Short Form-36, Oswestry Disability Index,
      Stenosis Bothersomeness Index, and Low Back Pain Bothersomeness Scale or the
      percent of patient satisfaction with symptoms averaged over the study period.
      CONCLUSIONS: The outcome scores associated with the use of posterior iliac crest
      bone graft for lumbar spinal fusion were not significantly lower than those after
      fusion without iliac crest autograft. Conversely, iliac crest bone-grafting was
      not associated with an increase in the complication rates or rates of
      reoperation. On the basis of these results, surgeons may choose to use iliac
      crest bone graft on a case-by-case basis for lumbar spinal fusion.

PMID- 22878600
TI  - Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid
      pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes.
AB  - Neurosteroids are known as allosteric modulators of the ligand-gated ion channel
      superfamily. Voltage-gated sodium channels (Na(v)) play an important role in
      mediating excitotoxic damages. Here we report the effects of neurosteroids on the
      function of Na(v), using voltage-clamp techniques in Xenopus oocytes expressed
      with the Na(v)1.2 alpha subunit. Pregnenolone sulphate, but not pregnenolone,
      inhibited sodium currents (I(Na)) at 3 - 100 MUmol/L. The suppression of I(Na) by
      pregnenolone sulphate was due to increased inactivation with little change in
      activation. These findings suggest that pregnenolone sulphate, a metabolite of
      pregnenolone, suppresses the function of Na(v) via increased inactivation, which
      may contribute to the neuroprotection.

PMID- 22878601
TI  - Serum levels of matrix metalloproteinase (MMP) 9, a risk factor for acute
      coronary syndrome, are reduced independently of serum MMP-3 by anti-TNF-alpha
      antibody (infliximab) therapy in patients with rheumatoid arthritis.
AB  - Matrix metalloproteinase 9 (MMP-9) is a risk factor for cardiovascular events.
      The serum MMP-9 levels were measured before and 2 weeks after treatment with
      infliximab (3 mg/kg) in 12 rheumatoid arthritis (RA) patients. The serum average
      MMP-9 level was 238.5 ng/ml before treatment with infliximab in RA patients
      (normal range: less than 43.8 ng/ml). Infliximab reduced the serum average MMP-9
      level significantly (161.66 ng/ml, P = 0.0425). The serum MMP-9 level was high in
      the RA patients with active disease, and it was reduced by infliximab
      independently of the reduction in disease activity. Thus, infliximab may reduce
      the risk of cardiovascular events directly.

PMID- 22878602
TI  - In vitro effects of VA441, a new selective cyclooxygenase-2 inhibitor, on human
      osteoarthritic chondrocytes exposed to IL-1beta.
AB  - The aim of this in vitro study was to examine the possible effect of [2-methyl-5
      (4-methylsulphonyl)phenyl-1-phenyl-3-(2-n-propyloxyethyl)]-1H-pyrrole (VA441), a
      new selective cyclooxygenase (COX)-2 inhibitor, on human osteoarthritic (OA)
      chondrocyte cultivated in the presence or absence of interleukin-1beta (IL
      1beta). In particular, we assessed the effects of 1 and 10 MUM of VA441,
      celecoxib, and indomethacin on cell viability, COX-2 and inducible nitric oxide
      synthase (iNOS) gene expression, prostaglandin E(2) (PGE(2)) production, and
      nitric oxide (NO) and metalloproteinase-3 (MMP-3) release. Furthermore, we
      carried out morphological assessment by transmission electron microscopy (TEM).
      The presence of IL-1beta led to a significant increase in PGE(2), MMP-3, and NO
      production, as well as a significant increase in gene expression of COX-2 and
      iNOS. All the drugs tested had a statistically significant inhibitory effect on
      PGE(2) production and gene expression of COX-2 stimulated by IL-1beta. VA441 and
      celecoxib significantly suppressed IL-1beta-stimulated MMP-3 and NO and iNOS gene
      expression in a dose-dependent manner, while indomethacin did not show any
      significant effect on MMP-3 and NO production or on iNOS gene expression. TEM
      demonstrated that IL-1beta severely alters the structure of chondrocytes; after
      co-incubation with VA441 or celecoxib, the cells recovered their ultrastructure.
      Our data suggest that VA441 and celecoxib may have a beneficial effect on
      chondrocyte metabolism.

PMID- 22878603
TI  - Telomeres and chromosomal instability in chronic lymphocytic leukemia.

PMID- 22878604
TI  - Encapsulated mesenchymal stem cells for in vivo immunomodulation.

PMID- 22878605
TI  - Effect of drying conditions during sample pre-treatment on the determination of
      polycyclic aromatic hydrocarbons in soils.
AB  - In the context of the entire analytical process, pre-treatment of soil samples is
      often inadequately considered although the reliability of the results is
      definitely compromised if the sample is not properly prepared. In this paper, the
      effect of drying conditions in soil sample pre-treatment on the determination of
      polycyclic aromatic hydrocarbons (PAHs) has been studied. A systematic approach
      has been adopted by varying soil type, drying temperatures and solvent polarity
      to highlight the effect on the analyte recovery; the relationship between PAH
      molecular structure and their evaporation process from soils is discussed.
      Experimental data demonstrate that, concerning temperature-assisted drying
      procedures, PAHs are divided in two distinct groups: PAHs lighter than pyrene,
      which are seriously affected by drying temperature; and heavier PAHs that can be
      considered as non-volatile compounds. For studies involving the analysis of
      lighter PAHs in environmental samples, working on as-received samples is
      necessary.

PMID- 22878606
TI  - John O. Susac, MD (1940-2012).

PMID- 22878607
TI  - Functionalized single-walled carbon nanotubes cause reversible acute lung injury
      and induce fibrosis in mice.
AB  - Nanotechnology is one of today's most promising technological developments, but
      safety concerns raise questions about its development. Risk assessments of
      nanomaterials during occupational exposure are crucial for their development.
      Here, we assessed the lung toxicity of functionalized single-walled carbon
      nanotube (f-SWCNT) exposure in C57BL/6 mice, elucidated the underlying molecular
      mechanism, and evaluated the self-repair ability and lung fibrosis of the mice.
      Soluble f-SWCNTs were administered to mice. After 18 h or 14 days, the lung
      histopathology, bronchoalveolar lavage fluid, lung edema, vascular permeability,
      and PaO(2) levels were evaluated, and biochemical and immunostaining tests were
      also performed. We found that some f-SWCNTs could induce acute lung injury (ALI)
      in mice via proinflammatory cytokine storm signaling through the NF-kappaB
      pathway in vivo. We illustrated that corticosteroid treatments could ameliorate
      the ALI induced by the f-SWCNTs in mice. Surprisingly, the ALI was almost
      completely reversed within 14 days, while mild to moderate fibrosis, granuloma,
      and DNA damage remained in the mice at day 14. Our studies indicate potential
      remedies to address the growing concerns about the safety of nanomaterials. In
      addition, we notify that the type of functional groups should be considered in
      nanomedicine application as differently functionalized SWCNTs generated different
      effects on the lung toxicity.

PMID- 22878608
TI  - Signal distortion from microelectrodes in clinical EEG acquisition systems.
AB  - Many centers are now using high-density microelectrodes during traditional
      intracranial electroencephalography (iEEG) both for research and clinical
      purposes. These microelectrodes are FDA-approved and integrate into clinical EEG
      acquisition systems. However, the electrical characteristics of these electrodes
      are poorly described and clinical systems were not designed to use them; thus, it
      is possible that this shift into clinical practice could have unintended
      consequences. In this study, we characterized the impedance of over 100
      commercial macro- and microelectrodes using electrochemical impedance
      spectroscopy (EIS) to determine how electrode properties could affect signal
      acquisition and interpretation. The EIS data were combined with the published
      specifications of several commercial EEG systems to design digital filters that
      mimic the behavior of the electrodes and amplifiers. These filters were used to
      analyze simulated brain signals that contain a mixture of characteristic features
      commonly observed in iEEG. Each output was then processed with several common
      quantitative EEG measurements. Our results show that traditional macroelectrodes
      had low impedances and produced negligible distortion of the original signal.
      Brain tissue and electrical wiring also had negligible filtering effects.
      However, microelectrode impedances were much higher and more variable than the
      macroelectrodes. When connected to clinical amplifiers, higher impedance
      electrodes produced considerable distortion of the signal at low frequencies (<60
      Hz), which caused significant changes in amplitude, phase, variance and spectral
      band power. In contrast, there were only minimal changes to the signal content
      for frequencies above 100 Hz. In order to minimize distortion with
      microelectrodes, we determined that an acquisition system should have an input
      impedance of at least 1 GOmega, which is much higher than most clinical systems.
      These results show that it is critical to account for variations in impedance
      when analyzing EEG from different-sized electrodes. Data from microelectrodes may
      yield misleading results unless recorded with high-impedance amplifiers.

PMID- 22878609
TI  - Expression analysis of aldehyde dehydrogenase 1A1 (ALDH1A1) in colon and rectal
      cancer in association with prognosis and response to chemotherapy.
AB  - BACKGROUND: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been described as a cancer
      stem cell marker and as a regulator of cellular chemoresistance. Therefore,
      ALDH1A1 has been suggested as potential biomarker to stratify patients into
      different risk categories for a "personalized" therapy approach. We have
      investigated the prognostic role of ALDH1A1 in primary colorectal cancer and its
      value in predicting response to chemotherapy in metastatic colorectal cancer.
      METHODS: Immunostaining against ALDH1A1 was performed on a paraffin-embedded
      tissue microarray including 659 primary colon cancer samples and 338 rectal
      cancer samples. Likewise, tissue of 44 palliatively resected colorectal liver
      metastases on whole-mount tissue slides was immunostained against ALDH1A1.
      Cytoplasmic, nuclear, and stromal expression of ALDH1A1 was assessed and merged
      with histopathological and clinical data. RESULTS: Univariate and multivariate
      analysis revealed that cytoplasmic and stromal expression of ALDH1A1 is not
      significantly associated with prognosis either in colon or in rectal cancer.
      Furthermore, cytoplasmic expression of ALDH1A1 does not predict response to
      palliative chemotherapy in patients with metastatic diseases. Intriguingly, as a
      novel finding, nuclear expression of ALDH1A1 was observed in a small subgroup of
      patients with colon cancer and rectal cancer. In colon cancer, nuclear expression
      was significantly associated with shortened overall survival by univariate and
      multivariate analysis. CONCLUSIONS: Immunohistochemical expression analysis of
      ALDH1A1 in colon cancer is useful for the detection of nuclear expression in a
      small subpopulation of patients and is associated with shorter survival.
      Cytoplasmic expression fails to be of clinical relevance as prognostic or
      predictive marker in colorectal cancer.

PMID- 22878610
TI  - Reconstruction patterns in a single institution cohort of women undergoing
      mastectomy for breast cancer.
AB  - OBJECTIVES: The purpose of the current study was to conduct a patient-centered
      investigation of reconstruction practices following mastectomy at our
      institution. METHODS: A questionnaire was administered to patients who underwent
      unilateral or bilateral mastectomy for breast cancer from 2006 to 2010. The
      survey queried on demographics, surgical choices, and rationale for those
      choices. Data were summarized by contingency tables and compared by chi-square
      test or Fisher's exact test, as appropriate. RESULTS: Of 321 patients queried,
      185 (58 %) underwent unilateral mastectomy and 136 (42 %) underwent bilateral
      mastectomy (mean age 56 +/- 12 years). Overall, 189 (59 %) women underwent breast
      reconstruction, and 132 (41 %) did not. Immediate breast reconstruction was
      performed in 125 of 189 (69 %) women, whereas 67 of 189 (31 %) underwent delayed
      reconstruction. The method of definitive reconstruction included 143 of 189 (75
      %) prostheses, 32 of 189 (17 %) abdominal tissue flap, 12 of 189 (6 %) latissimus
      flap (+/-implant), and 5 of 189 (2 %) with a combination of prostheses and tissue
      flaps. Of the 114 patients who did not undergo reconstruction, 68 (60 %) reported
      lack of desire for reconstruction as their motive, and the remaining 46 (40 %)
      reported medical contraindications for reconstruction or did not report a
      specific reason. CONCLUSIONS: A significant percentage of women undergoing
      unilateral or bilateral mastectomy for breast cancer at our institution elect to
      undergo reconstruction. Prosthetic reconstruction was the most common method
      utilized. The impetus for referral to the reconstructive surgeon was nearly
      always initiated by the surgical oncologist.

PMID- 22878611
TI  - ABO blood type/Rh factor and the incidence and outcomes for patients with triple
      negative breast cancer.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) has a poorer prognosis; the
      factors that contribute to this remain unclear. We hypothesized that TNBC is
      associated with ABO blood type/Rh factors that account for differences in
      survival. METHODS: We identified 468 patients with stage I-III TNBC [estrogen
      receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2
      nonamplified]. Patient/tumor characteristics, treatments, and outcomes were
      obtained. Data were examined for associations with specific ABO blood type/Rh
      factors. Descriptive statistics and chi (2) analysis were utilized for data
      summary and comparisons. RESULTS: Of 468 TNBC patients, 283 had known ABO blood
      type [122 (43 %) O, 108 (38 %) A, 39 (14 %) B, and 14 (5 %) AB] and Rh factor
      [253 (89 %) positive and 30 (11 %) negative]. Mean patient age was 53.7 +/- 12.5
      years, and median follow-up was 30.2 +/- 20.5 months. The incidence of each ABO
      blood type/Rh factor in our TNBC cohort was not different from the general
      population or a cohort of ER-positive breast cancers (P > 0.05). Compared with
      patients with blood type O, there was no difference in breast cancer-specific
      mortality for type A [hazard ratio (HR) 0.906; 95 % confidence interval (CI)
      0.554-1.481], type B (HR 1.534; 95 % CI 0.792-2.972), or type AB (HR 0.488; 95 %
      CI 0.113-2.106). Compared with women with negative Rh, there was no difference in
      breast cancer-specific mortality for women with positive Rh (HR 1.161; 95 % CI
      0.568-2.374). CONCLUSIONS: TNBC was not associated with a specific ABO blood type
      or Rh factor. Our results failed to demonstrate an association between ABO blood
      type/Rh factor and breast cancer mortality in patients with TNBC.

PMID- 22878612
TI  - Autologous inferior dermal sling (autoderm) with concomitant skin-envelope
      reduction mastectomy: an excellent surgical choice for women with macromastia and
      clinically significant ptosis.
AB  - BACKGROUND: Skin-sparing mastectomy and prosthetic reconstruction can be
      complicated by poor surgical outcomes in large-breasted, obese women. This
      article describes a single surgeon's experience comparing conventional skin
      sparing mastectomy (SSM) and skin-reduction mastectomy using an autologous
      vascularized inferior dermal/cutaneous sling (autoderm). METHODS: From July 2007
      to May 2012, patients undergoing skin-sparing mastectomy were evaluated for
      surgical outcomes. After July 2009, the surgeon performed skin-reduction
      mastectomies with autoderm (SRM-AD) on all patients with macromastia or grade 3-4
      ptosis. Remaining patients in this time period (SSM-cont) underwent conventional
      skin-sparing mastectomies while all previous patients (historical) also underwent
      skin-sparing mastectomies (SSM-hist). A predictive model was used to compare the
      large historical patients (who would have had reduction mastectomy if available)
      with the smaller historical patients to evaluate the effect of the procedure.
      RESULTS: Body mass index (BMI) and specimen weight were higher in both the SRM
      group and large historical group. The hazard ratio for having skin-reduction
      mastectomy was 0.53 (P = 0.51) compared with the historical group. There was a
      total of 16 complications for the whole study. Smoking was the only significant
      risk factor. CONCLUSIONS: This study shows that mastectomy with prosthetic
      reconstruction using a skin-reduction technique with autoderm can be done safely
      with a low complication rate and improved cosmetic outcomes in the traditionally
      "at-risk" group of women with high BMI and large ptotic breasts.

PMID- 22878613
TI  - Presentation and management of gastrointestinal stromal tumors of the duodenum: a
      multi-institutional analysis.
AB  - BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are a small subset
      of GISTs, and their management is poorly defined. We evaluated surgical
      management and outcomes of patients with duodenal GISTs treated with
      pancreaticoduodenectomy (PD) versus local resection (LR) and defined factors
      associated with prognosis. METHODS: Between January 1994 and January 2011, 96
      patients with duodenal GISTs were identified from five major surgical centers.
      Perioperative and long-term outcomes were compared based on surgical approach (PD
      vs LR). RESULTS: A total of 58 patients (60.4%) underwent LR, while 38 (39.6%)
      underwent PD. Patients presented with gross bleeding (n = 25; 26.0%), pain (n =
      23; 24.0%), occult bleeding (n = 19; 19.8%), or obstruction (n = 3; 3.1%). GIST
      lesions were located in first (n = 8, 8.4%), second (n = 47; 49%), or
      third/fourth (n = 41; 42.7%) portion of duodenum. Most patients (n = 86; 89.6%)
      had negative surgical margins (R0) (PD, 92.1 vs LR, 87.9%) (P = 0.34). Median
      length of stay was longer for PD (11 days) versus LR (7 days) (P = 0.001). PD
      also had more complications (PD, 57.9 vs LR, 29.3%) (P = 0.005). The 1-, 2-, and
      3-year actuarial recurrence-free survival was 94.2, 82.3, and 67.3%,
      respectively. Factors associated with a worse recurrence-free survival included
      tumor size [hazard ratio (HR) = 1.09], mitotic count >10 mitosis/50 HPF (HR =
      6.89), AJCC stage III disease (HR = 4.85), and NIH high risk classification (HR =
      4.31) (all P < 0.05). The 1-, 3-, and 5-year actuarial survival was 98.3, 87.4,
      and 82.0%, respectively. PD versus LR was not associated with overall survival.
      CONCLUSIONS: Recurrence of duodenal GIST is dependent on tumor biology rather
      than surgical approach. PD was associated with longer hospital stays and higher
      risk of perioperative complications. When feasible, LR is appropriate for
      duodenal GIST and PD should be reserved for lesions not amenable to LR.

PMID- 22878614
TI  - Prognostication of vulvar cancer based on p14ARF status: molecular assessment of
      transcript and protein.
AB  - PURPOSE: This study was designed to determine the prognostic role of p14ARF in
      vulvar squamous cell carcinoma (VSCC). METHODS: Immunohistochemistry for p14ARF
      and p53 and fluorescent in situ hybridization (FISH) for TP53 were performed in
      139 cases of VSCC. Human papillomavirus (HPV) genotyping by hybridization was
      employed in 100 cases. qRT-PCR for p14ARF and p53 transcript assessment was
      performed in 16 cases. All results were correlated with clinicopathological
      variables. RESULTS: Immunohistochemistry analysis showed p14ARF and p53
      positivity in 16.4% and 53% cases respectively. Positive p14ARF expression was
      significantly associated with the following variables: shorter cancer-specific
      survival (P=0.04) and shorter disease-free survival (P=0.02), presence of
      perineural invasion (P=0.037), vascular invasion (P=0.047), and node metastasis
      (P=0.031). Also, p14ARF-positive HPV-negative cases had the shortest cancer
      specific survival (P=0.03) and disease-free survival (P=0.04). HPV infection was
      detected in 32.8% of the cases; HPV16 was the most prevalent type. Viral
      infection was more common in poorly differentiated tumors (P=0.032). qRT-PCR
      demonstrated that CDKN2A (p14ARF) had higher expression in tumor samples compared
      with paired noncancerous samples (P<0.001). The opposite relationship was seen in
      TP53 expression evaluation (P<0.001). FISH demonstrated 4 cases with deleted TP53
      (6.3%). CONCLUSIONS: p14ARF represents an important marker of poor prognosis in
      VSCC. p53 and HPV infection did not show any prognostic importance. Further
      clinical trials concerning p14ARF positivity may result in important
      contributions due to its relationship with poor outcome. Mainly due to the
      relationship of p14ARF with lymph node metastasis, the immunohistochemistry
      evaluation of this marker may help to identify a subset of patients more suitable
      to less radical procedures.

PMID- 22878615
TI  - Oncological safety of autologous lipoaspirate grafting in breast cancer patients:
      a systematic review.
AB  - BACKGROUND: Autologous lipoaspirate grafting (ALAG) has become a widely used
      treatment in breast reconstruction after mastectomy (MST) or breast-conserving
      treatment (BCT), although there is an ongoing debate about its oncological
      safety. The aim of this systematic review was to identify, evaluate, and
      synthesize all clinical evidence examining the oncological risks associated with
      the procedure. METHODS: An extensive electronic search was performed in PubMed,
      Embase, and the Cochrane Library using the keywords "breast" and "autologous
      lipoaspirate grafting" and synonyms. RESULTS: The search yielded a total of 269
      unique hits. Twenty clinical trials investigated ALAG in breast reconstruction
      after cancer. Although nine of them provided oncological follow-up data, only one
      retrospective cohort and four case series were suitable for analysis. The former
      reported no significant differences in the locoregional recurrence (LRR)
      incidence rates between the intervention and control groups for patients with MST
      as well as BCT. A large multicenter case series reported LRR incidence rates of
      1.35 and 2.19 for MST and BCT patients, respectively. The remaining two series
      were far smaller trials with shorter follow-up and reported no recurrences. No
      randomized, controlled trials were identified. Most of the available studies
      consisted of cohorts and case series with short follow-up and no control
      subjects. CONCLUSIONS: Although the first reports on cancer recurrence after ALAG
      are inconclusive, they show promising results. Whether lipoaspirate grafting
      promotes LRR in breast cancer patients is still unclear. To be able to answer
      this question, larger prospective trials with longer follow-up are needed.

PMID- 22878616
TI  - Expression of the RET proto-oncogene is regulated by TFAP2C in breast cancer
      independent of the estrogen receptor.
AB  - BACKGROUND: The RET proto-oncogene is expressed as part of the estrogen receptor
      (ER) cluster in breast cancer. We sought to determine if TFAP2C regulates Ret
      expression directly or indirectly through ER. METHODS: Chromatin
      immunoprecipitation sequencing (ChIP-Seq) and gel-shift assay were used to
      identify TFAP2C binding sites in the RET promoter in four breast cancer cell
      lines. Ret mRNA and protein levels were evaluated in ER-positive and ER-negative
      breast cancer cell lines after knockdown of TFAP2C. Luciferase expression assay
      was performed to assess expression from two of the identified sites. RESULTS:
      ChIP-Seq identified five main binding peaks for TFAP2C in the RET promoter at 
      101.5 kb, -50.7 kb, -32.5 kb, +5.0 kb, and +33.6 from the RET transcriptional
      start site. Binding at three of the AP-2 sites was conserved across all four cell
      lines, whereas the RET -101.5 and RET +33.6 sites were each found to be unbound
      by TFAP2C in one cell line. A TFAP2C consensus element was confirmed for all five
      sites. Knockdown of TFAP2C by siRNA in ER-positive MCF-7 cells resulted in
      significant down regulation of Ret mRNA compared to nontargeting (NT) siRNA (0.09
      vs. 1.0, P < 0.001). Knockdown of TFAP2C in ER-negative MDA-MB-453 cells also led
      to a significant reduction in Ret mRNA compared to NT siRNA (0.16 vs. 1.0, P <
      0.001). In MCF-7 cells, knockdown of TFAP2C abrogated Ret protein expression
      (0.02 vs. 1.0, P < 0.001) before reduction in ER. CONCLUSIONS: TFAP2C regulates
      expression of the RET proto-oncogene through five AP-2 regulatory sites in the
      RET promoter. Regulation of Ret by TFAP2C occurs independently of ER expression
      in breast carcinoma.

PMID- 22878617
TI  - Advanced imaging modalities in early stage breast cancer: preoperative use in the
      United States Medicare population.
AB  - BACKGROUND: Guidelines for breast cancer staging exist, but adherence remains
      unknown. This study evaluates patterns of imaging in early stage breast cancer
      usually reserved for advanced disease. METHODS: Surveillance Epidemiology, and
      End Results data linked to Medicare claims from 1992-2005 were reviewed for stage
      I/II breast cancer patients. Claims were searched for preoperative performance of
      computed tomography (CT), positron emission tomography (PET), bone scans, and
      brain magnetic resonance imaging (MRI) ("advanced imaging"). RESULTS: There were
      67,874 stage I/II breast cancer patients; 18.8% (n=12,740) had preoperative
      advanced imaging. The proportion of patients having CT scans, PET scans, and
      brain MRI increased from 5.7% to 12.4% (P<0.0001), 0.8% to 3.4% (P<0.0001) and
      0.2% to 1.1% (P=0.008), respectively, from 1992 to 2005. Bone scans declined from
      20.1% to 10.7% (P<0.0001). "Breast cancer" (174.x) was the only diagnosis code
      associated with 62.1% of PET scans, 37.7% of bone scans, 24.2% of CT, and 5.1% of
      brain MRI. One or more symptoms or metastatic site was suggested for 19.6% of
      bone scans, 13.0% of CT, 13.0% of PET, and 6.2% of brain MRI. Factors associated
      (P<0.05) with use of all modalities were urban setting, breast MRI and
      ultrasound. Breast MRI was the strongest predictor (P<0.0001) of bone scan (odds
      ratio [OR] 1.63, 95% confidence interval [CI] 1.44-1.86), Brain MRI (OR 1.74, 95%
      CI 1.15-2.63), CT (OR 2.42, 95% CI 2.12-2.76), and PET (OR 5.71, 95% CI 4.52
      7.22). CONCLUSIONS: Aside from bone scans, performance of advanced imaging is
      increasing in early stage Medicare breast cancer patients, with limited rationale
      provided by coded diagnoses. In light of existing guidelines and increasing
      scrutiny about health care costs, greater reinforcement of current indications is
      warranted.

PMID- 22878619
TI  - Atypical ductal hyperplasia on core biopsy: an automatic trigger for excisional
      biopsy?
AB  - INTRODUCTION: Excisional biopsy is currently recommended for atypical ductal
      hyperplasia (ADH) diagnosed on core needle breast biopsy (CNB), due to risk of
      upstaging to invasive or in situ carcinoma (DCIS). The study goal was to identify
      patients who may potentially forego excisional biopsy if the risk of upstaging is
      low. METHODS: We conducted a retrospective review of patients diagnosed with ADH
      on CNB who underwent excisional biopsy at one institution (5/2000-5/2011). We
      evaluated the upstaging rate and clinicopathologic factors associated with
      increased upstaging risk. RESULTS: A total of 114 cases of ADH were diagnosed on
      CNB. The median patient age was 64 years. On mammography, a mass/density/area of
      distortion was present in 23 % of cases; calcifications were present in 77 %.
      Most biopsies (79 %) were performed stereotactically. Twenty lesions (18 %) were
      upstaged to infiltrating carcinoma (5 %) or DCIS (13 %). Residual ADH was present
      in 43 biopsies (38 %). On univariate analysis, significant variables associated
      with upstaging included age >50 years, a mass lesion on mammography, and shorter
      length of biopsy core (p < 0.05). No patient <=50 years of age was upstaged.
      Three patients who were not upstaged (3 %) developed ipsilateral disease (2 DCIS
      and 1 infiltrating ductal carcinoma) at a median time of 37 months. CONCLUSIONS:
      The rate of upstaging when ADH is diagnosed on CNB at our institution is 18 %,
      and routine excisional biopsy is currently recommended for all patients. However,
      patients <50 years old with focal atypia only and no residual calcifications
      postbiopsy may represent a low-risk group who could potentially avoid excisional
      biopsy.

PMID- 22878620
TI  - Pediatric and adolescent synovial sarcoma: multivariate analysis of prognostic
      factors and survival outcomes.
AB  - PURPOSE: Treatment of synovial sarcoma (SS) is challenging because of its
      unpredictable clinical behavior. We reviewed our institutional experience with
      pediatric SS to identify prognostic indicators and survival outcomes. METHODS: We
      retrospectively reviewed all pediatric/adolescent patients (age<22 years) with
      confirmed SS treated from 1970 to 2010. Patient and clinical characteristics were
      evaluated for prognostic significance and survival outcomes. RESULTS: We
      identified 111 patients. The median age was 15.4 years. Sixty-seven tumors (60%)
      were monophasic, 42 (38%) were biphasic, and 2 (2%) were of unknown histology.
      Median follow-up was 5.3 years (range 0.8-36.8 years), 5-year overall survival
      (OS) was 73%, and 10-year OS was 65%. Greater tumor size (stratified as <=5 cm,
      >5 cm, or >=10 cm) (P=0.001) and depth (P=0.03) correlated with decreased OS.
      Primary tumor location in the upper extremity correlated with increased OS when
      compared with lower-extremity and central lesions (P=0.05). Bone and/or
      neurovascular invasion negatively impacted survival (P=0.02). Multivariate
      analysis revealed that tumor size (trichotomized) was the dominant and sole
      factor in discriminating survival risk. Neither radiotherapy nor chemotherapy
      correlated with improved 5-year survival. CONCLUSIONS: Tumor size, depth,
      invasion, and primary location affect survival in pediatric SS. The role of
      radiotherapy and chemotherapy for SS warrants future study.

PMID- 22878618
TI  - Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation
      induced malignant peripheral nerve sheath tumors.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically,
      after prior radiation therapy (RT), or in association with neurofibromatosis type
      1 (NF1). It is controversial whether patients with NF1-associated MPNST have
      worse outcomes. We investigated the prognostic significance of sporadic, NF1
      associated, and RT-induced MPNST. METHODS: Patients with primary high-grade MPNST
      from 1982 to 2011 were identified from a prospectively maintained database.
      Patients with sporadic MPNST were included only if the MPNST was not associated
      with NF1 or a neurofibroma or if it was immunohistochemically S100-positive.
      RESULTS: We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and
      14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for
      surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced
      tumors and 9.7 cm for NF1-associated and sporadic tumors (P=0.004). In
      multivariate analysis, factors associated with worse disease-specific survival
      (DSS) were larger size (HR 1.08; 95% CI 1.04-1.13; P<0.001) and positive margin
      (HR 3.30; 95% CI 1.74-6.28; P<0.001). Age, gender, site of disease, and S100
      staining were not associated with DSS. The 3-year and median DSS were similar for
      NF1 and sporadic cases; combined 3-year DSS was 64% and median DSS was 8.0 years.
      For RT-induced tumors, 3-year DSS was 49% and median DSS was 2.4 years. The
      relationship between RT association and DSS approached statistical significance
      (HR 2.29; 95% CI 0.93-5.67; P=0.072). CONCLUSIONS: Margin status and size remain
      the most important predictors of DSS in patients with MPNST. NF1-associated and
      sporadic MPNSTs may be associated with improved DSS compared with RT-induced
      tumors.

PMID- 22878621
TI  - Nonmalignant breast papillary lesions at core-needle biopsy: a meta-analysis of
      underestimation and influencing factors.
AB  - BACKGROUND: The clinical management of nonmalignant breast papillary lesions
      diagnosed at core-needle biopsy (CNB) is controversial. A meta-analysis was
      performed to evaluate pooled estimates of the underestimation of malignant
      papillary lesions (which were diagnosed as nonmalignant lesions at CNB) and to
      survey factors that affect that underestimation. METHODS: We searched for studies
      that provided data on CNB underestimates of malignant breast papillary lesions
      indexed in PUBMED. The pooled estimate for underestimation was calculated. The
      association between each variable and underestimation was investigated using
      either random- or fixed-effects logistic modeling. RESULTS: A total of 34
      studies, which included 2,236 nonmalignant breast papillary lesions diagnosed at
      CNB and histologically examined after surgical excision, were included. Of these,
      346 nonmalignant lesions at CNB were upgraded to malignant after surgical
      excision. The pooled estimate for the percentage of underestimation was 15.7%
      [95% confidence interval (CI): 12.8-18.5%]. The factors associated with higher
      underestimation included atypical papillary lesions (P<0.001), positive
      mammographic findings (P=0.022), and article publication year before 2005
      (P<0.05). CONCLUSIONS: It is recommended that atypical papillary lesions at CNB
      undergo surgical excision, and it is reasonable to follow patients with benign
      lesions with serial imaging. Lesion type, mammographic findings, and article
      publication year were significantly associated with underestimation.

PMID- 22878622
TI  - Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and
      benzo[b]furans: synthesis of benzo[b]thiophene 2,3-oxide.
AB  - Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several
      methyl substituted derivatives was found to occur in both the carbocyclic and
      heterocyclic rings. Relative and absolute configurations and enantiopurities of
      the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in
      carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions
      of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable
      heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong
      preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol
      metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic
      synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.

PMID- 22878624
TI  - Diagnosis and management of pulmonary vasculitis.
AB  - The pulmonary vasculitides are a heterogeneous group of disorders characterized
      pathologically by vascular destruction with cellular inflammation and necrosis.
      These disorders can affect small, medium, and large vessels and may be primary or
      occur secondary to a variety of conditions. Vasculitis involving the lungs is
      most commonly due to primary, idiopathic, small-vessel antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitides, which includes granulomatosis with
      polyangiitis (formerly Wegener's granulomatosis), Churg-Strauss syndrome, and
      microscopic polyangiitis. From a clinical perspective these remain among the most
      challenging of diseases both in terms of diagnosis and treatment. This review
      will focus on diagnosis and management of ANCA-associated vasculitides.

PMID- 22878623
TI  - Monovision: a refractive consideration in cataract surgery after vitrectomy?
AB  - Cataract is the most common complication of vitrectomising surgery in the phakic
      eye. Progressive nuclear sclerosis (NS) causes a myopic shift. This change in
      refractive status can predispose to the development of monovision in presbyopic
      individuals. Recognition of adaptation to monovision is important when
      undertaking sequential cataract surgery. Our case describes a patient whose
      adaptation to monovision was only recognised after its reversal. Predisposing
      factors are discussed and lessons highlighted.

PMID- 22878625
TI  - A review of current bronchoscopic interventions for obstructive airway diseases.
AB  - Obstructive diseases of the airway are a diverse group, although they share in
      common airway narrowing as a sequel to inflammation, which leads to increased
      work of breathing. Optimal treatment strategies for this heterogeneous group of
      asthma, chronic bronchitis and emphysema should be multidimensional and embrace
      pharmacological and nonpharmacological means as well as surgery in a highly
      select group of patients with emphysema. We review the current status of the
      bronchoscopic interventions that have been in development for the past decade
      with the objectives of providing better symptom control in asthma and palliation
      in individuals with emphysema who are otherwise poor candidates for lung volume
      reduction surgery.

PMID- 22878626
TI  - Optimization of a commercial biosensor for polychlorinated biphenyls and
      evaluation of its utility for screening.
AB  - We previously described our systematic progress that eventually resulted in a
      commercially available immunoassay based biosensor (PCB biosensor) for detecting
      PCBs in oil.  However, IC50 of the commercialized PCB biosensor was approximately
      2 ppb for PCBs, and did not achieve the theoretical detection limit (TDL) which
      would represent an IC50 of approximately 0.5 ppb.  In this study, we characterize
      the effects of the antibody concentration, flow volume and flow rate on the PCB
      biosensor's response.  Using the optimum operating conditions, the PCB biosensor
      achieved the TDL and its performance as a screening test was improved.  Working
      at the stringent maximum residue limit specified by Japanese law (0.5 ppm total
      PCBs), the optimized biosensor exhibited excellent performance (0% false
      negatives and 7% false positives) in the screening of 110 samples of used
      Japanese transformer oil.  The general approach for optimization described here
      is expected to benefit immunoassay researchers attempting to achieve optimum
      performance.

PMID- 22878627
TI  - A fluorescent pH chemosensor based on functionalized naphthalimide in aqueous
      solution.
AB  - The synthesis of functionalized naphthalimide (compound 1) and its application
      for the preparation of pH chemosensor was described. The fluorescence enhancement
      of compound 1 with the increase of hydrogen ion concentration is based on the
      hindering of photo-induced electron transfer (PET) from aliphatic amine group to
      the naphthalimide. The comparison of this method with some other fluorescence
      methods based on naphthalimide for the measurement of pH indicated that the
      method can be applied in aqueous solutions rather than organic solutions. The
      analytical performance characteristics of the proposed pH chemosensor were also
      investigated. The chemosensor can be applied to the determination of pH between
      3.20 and 7.80. Common inorganic ions do not show obvious interference for pH
      measurements. Moreover, the response of the chemosensor for pH is fast (response
      time less than 3 min). In addition, the chemosensor has been used for
      determination of pH in urine samples with satisfactory results.

PMID- 22878628
TI  - A "turn-on" fluorescent chemosensor based on peptidase for detecting copper(II).
AB  - A new fluorescent chemosensor for Cu(II) ions was designed and synthesized on the
      basis of the sequence-specific cleavage of the peptide bond by the peptidase
      (metal or metal complexes). In the chemosensor system, the substrate was labeled
      with a FAM fluorophore (6-carboxyfluorescein) at the N-terminal and with a Dabcyl
      quencher 4-(4'-dimethylaminophenylazo)benzoic acid at the epsilon-N of C-terminal
      Lys. In the presence of Cu(II), the substrate strand is cleaved, and the release
      of the cleaved fragment results in a significant fluorescence increase. The
      design was aided by the FRET study that showed a "turn-on" response for Cu(II) in
      an aqueous medium. Under optimum conditions, the novel chemosensor described here
      had a linear response range for Cu(II) from 1.0 * 10(-8) to 1.0 * 10(-6) mol dm(
      3) with a detection limit of 1.0 * 10(-8) mol dm(-3).

PMID- 22878629
TI  - Improved performance of antigen-HRP conjugate-based immunoassays after the
      addition of anti-HRP antibody and application of a liposomal chemiluminescence
      marker.
AB  - To overcome the sensitivity limit for small molecules (haptens) in immunoassays
      based on antigen-horseradish peroxidase (HRP) conjugates as labels, a novel
      approach was established that afforded very low detection limits. Biotinylated
      anti-HRP antibody was utilized in order to attach, via a streptavidin bridge,
      liposomaly entrapped HRP. Fentanyl, used as a model antigen, could be determined
      via the generation of a high-intensity and relatively stable chemiluminescence
      (CL) signal of a HRP-catalyzed luminol/H(2)O(2)/enhancer system, immediately
      after the addition of a substrate solution. 4-(1-Imidazolyl)phenol (4-IMP) was
      used as an enhancer, and the outcome of this combination was a very low detection
      limit (0.895 pg mL(-1)) in plasma samples. The respective detection limit with
      the use of just the classical HRP-antigen conjugate was > 5-times higher. Intra-
      and inter-assay RSDs of the novel assay were 6.8 - 9.9 and 11 - 17%,
      respectively. The proposed method could be utilized for a wide range of molecules
      without replacing existing antigen-HRP based kits.

PMID- 22878630
TI  - Excitation processes in introduction of bias current to a radio-frequency glow
      discharge plasma evaluated from Boltzmann plots of iron atomic and ionic spectral
      lines.
AB  - A DC current, which was driven by the self-bias voltage, could be conducted in a
      radio-frequency-powered glow discharge plasma by connecting a low-pass filter
      circuit and a load resistor with the discharge tube.  This current enhanced the
      intensity of emission spectra from the plasma largely.  The intensities of iron
      atomic lines increased 35 - 50 times, whereas the sputtering rate was not changed
      by the current introduction.  Boltzmann plots for iron atomic (Fe I) and ionic
      lines (Fe II) were investigated when the bias current was conducted, so that the
      excitation process relating to the intensity increase could be clarified.  While
      the excitation temperature of the Fe I lines was slightly changed (3000 - 3600
      K), that of the Fe II lines was drastically reduced from 7600 to 4300 K, which
      was close to the temperature of the Fe I lines at higher bias currents. 
      Therefore, the plasma was changed towards an LTE condition so that both the Fe I
      and the Fe II lines could be excited through a common major process.  The bias
      current enhanced the density of electrons enabling low-lying excited energy
      levels (3 - 5 eV) of iron atom/ion to be much more populated, and they became the
      major colliding partners for the excitation of these iron species.

PMID- 22878631
TI  - Synthesis of cellulose functionalized with polyallylamine and its application to
      on-line collection/concentration and determination of phosphate by ICP/AES.
AB  - A novel cellulose-based resin functionalized with polyallylamine was synthesized.
      It was applied to the collection of phosphate in environmental water samples,
      followed by concentration determination using an inductively coupled plasma
      atomic emission spectrometer (ICP/AES). The synthesized resin, cellulose
      glycidylmethacrylate-polyallylamine (CGP), showed good adsorption behavior toward
      trace amounts of phosphate over a wide pH range. The adsorbed-analyte can be
      easily eluted using 0.5 M hydrochloric acid; its recoveries was found to be 80 -
      100%. The CGP resin synthesized was packed in a mini-column, which was then
      installed in a computer-controlled auto-pretreatment system for on-line
      collection/concentration and determination of trace phosphate by ICP/AES. The
      limit of detection for phosphate was found to be 0.6 ug P l(-1). The sample
      volumes were only 5 ml and the total analysis time was about 4 min. The developed
      method with CGP resin was successfully applied to the determination of phosphate
      in river water and tap water samples with satisfactory results. The recovery test
      showed that common matrices that may exist in environmental waters did not
      interfere with the determination of phosphate.

PMID- 22878632
TI  - Aqueous extraction of water-soluble inorganic arsenic in marine algae for
      speciation analysis.
AB  - An aqueous extraction of inorganic As species, such as arsenite (As(III)) and
      arsenate (As(V)), was developed for monitoring inorganic As in the edible brown
      alga Hizikia fusiforme (hijiki). The ultrasonic extraction with water, even
      without heating, was found to be an acceptable monitoring method for an
      evaluation of water-soluble inorganic As, since it could extract about 80% of
      total As. Such an extraction efficiency was almost the same as those of enzyme
      assisted extraction methods. The developed extraction procedure was applied to 15
      hijiki samples that had been collected at different coasts in Japan. All samples
      contained a substantial proportion of As as arsenosugars; the relative amounts of
      the different As species extracted were dependent on the sample. The percentages
      of extractable As species in the hijiki samples were in the range from 70 to 90%,
      and the sums of the concentrations of As(III) and As(V), which was defined as i
      As, were in the range from 36 to 79% of the total As concentration in each
      sample. The proposed method is appropriate for environmental monitoring for
      inorganic As speciation in algae.

PMID- 22878633
TI  - A negative-pressure flow-injection micro-electrode system for rapid and
      simultaneous determination of four electrolytes in human serums.
AB  - An automatic system for simultaneous determination of K(+), Na(+), Cl(-) and
      Ca(2+) in serums was established on the basis of a negative-pressure flow
      injection using micro-electrodes, and parameters of the system were optimized.
      The total ionic strength adjustment buffer consisted of 0.25 mmol L(-1) K(+),
      48.6 mmol L(-1) Na(+), 2.56 mmol L(-1) Cl(-), 0.25 mmol L(-1) Ca(2+) and 23 mmol
      L(-1) Na(2)B(4)O(7)-H(3)BO(3); the flow rate was 1.58 mL min(-1), the sampling
      volume was 45 uL, and the mixing coil length was 30 cm. The system could conduct
      480 detections h(-1), and its RSD was less than 1.6%. Recoveries were 97.3 -
      103.6%, and linear responses were 2.0 - 22.0 mmol L(-1) for K(+), 89.6 - 253.0
      mmol L(-1) for Na(+), 20.1 - 248.2 mmol L(-1) for Cl(-), and 0.35 - 10.0 mmol L(
      1) for Ca(2+), respectively. The ion concentration ranges were in ranges of human
      serum electrolytes. The system features minimized sorption of fibrin in sensors
      and prolonged sensor life.

PMID- 22878634
TI  - Quantitative analyses of the isoforms of surfactin produced by Bacillus subtilis
      HSO 121 using GC-MS.
AB  - Lipopeptide is one of the most important biosurfactants. The content of each
      isoform of a lipopeptide is crucial to the study of the properties of metabolites
      as well as the biological and biochemical characters of microbes. However, this
      information has not been accurately provided by the current analysis method. A
      new method for the quantitative determination of each isoform in the surfactin
      family has been established. The surfactin was firstly hydrolyzed in an acid
      solution at 90 degrees C for 20 h, dried and then treated with
      bis(trimethylsilyl)trifluoroacetamide at 60 degrees C for 20 min. The derived
      hydrolysates were then analyzed by GC-MS for a quantitative determination via
      comparison with working curves made with amino acids. GC-MS analyses show that
      the nine isoforms with an amount of 4.80 * 10(-7) mol (493 ug) in a 500 ug
      surfactin sample were detected, in which the mole fractions of surfactin isoforms
      with different fatty acid chains were 0.32% (n C(12)), 4.89% (iso C(13)), 6.27%
      (anteiso C(13)), 23.05% (iso C(14)), 8.95% (n C(14)), 17.69% (iso C(15)), 38.69%
      (anteiso C(15)), 0.07% (iso C(16)), and 0.07% (n C(16)), respectively. This
      approach can be applied to quantitative analyses for other families of
      lipopeptides as long as the sequence of amino acid residues in the peptide is
      determined.

PMID- 22878635
TI  - Simultaneous speciation of iron(II) and iron(III) by ion chromatography with
      chemiluminescence detection.
AB  - This study reports on a method for the speciation of iron in aqueous samples by
      the simultaneous analysis of divalent and trivalent iron ions with ion
      chromatography equipped with chemiluminescence detection (IC-CLD). Ferrous and
      ferric ions are first chelated by pyridine-2,6-dicarboxylic acid (PDCA) to form
      complexed anions, and separated by a mixed-bed ion-exchange column. The separated
      complexed ions are then detected with a CLD system containing luminol and
      hydrogen peroxide in a basic solution. This luminescence system has a linear
      dynamic range of ca. 3 orders of magnitude, with method detection limits as low
      as 7 ug L(-1) for Fe(II) and 3 ug L(-1) for Fe(III), measured in the simultaneous
      detection mode. This system resists interferences from common cations such as Cd,
      Ca, Cr, Cu, Mg, Ni, Pb, and Zn. Evaluation by analyzing real samples shows that
      this method is rapid, accurate, sensitive, and selective.

PMID- 22878637
TI  - Influence of speciation on the response from selenium to UV-photochemical vapor
      generation.
AB  - By exposure to appropriate UV intensities, rapid and quantitative
      oxidation/reduction of inorganic selenite, selenate and several organoselenium
      compounds representative of those of biochemical/metabolic interest, including
      selenomethionine, selenobetaine, L-selenocystine, selenomethylselenocysteine,
      gamma-glutamyl-seleno-methylselenocysteine and selenocystamine, is achieved. In
      the presence of acetic acid, quantitative conversion to volatile SeH(2) and SeCO
      occurs using a flow-through system comprising a highly efficient 40 W UV lamp for
      oxidation in tandem with a lower power 8 W UV photocatalytic reactor utilizing a
      thin-film coating of titania. The volatile reduced species are detected by atomic
      absorption spectrometry using a heated quartz tube atomizer. Direct photochemical
      conversion of selenite, selenomethionine, L-selenocystine, gamma-glutamyl-Se
      methylselenocysteine and selenocystamine occurs in the presence of 5% acetic
      acid, following exposure to an 8 W UV field, to yield volatile detectable
      species, whereas selenobetaine and selenate are unresponsive unless the latter is
      first subjected to oxidation by exposure to a highly efficient 40 W UV lamp and
      the selenate reduced in the presence of titania.

PMID- 22878636
TI  - Quantile normalization approach for liquid chromatography-mass spectrometry-based
      metabolomic data from healthy human volunteers.
AB  - In metabolomic research, it is important to reduce systematic error in
      experimental conditions. To ensure that metabolomic data from different studies
      are comparable, it is necessary to remove unwanted systematic factors by data
      normalization. Several normalization methods are used for metabolomic data, but
      the best method has not yet been identified. In this study, to reduce variation
      from non-biological systematic errors, we applied 1-norm, 2-norm, and quantile
      normalization methods to liquid chromatography-mass spectrometry (LC-MS)-based
      metabolomic data from human urine samples after oral administration of
      cyclosporine (high- and low-dose) in healthy volunteers and compared the
      effectiveness of the three methods. The principal component analysis (PCA) score
      plot showed more obvious groupings according to the cyclosporine dose after
      quantile normalization than after the other two methods and prior to
      normalization. Quantile normalization is a simple and effective method to reduce
      non-biological systematic variation from human LC-MS-based metabolomic data,
      revealing the biological variance.

PMID- 22878638
TI  - Proteomics of the rodent malaria parasite using matrix-assisted laser
      desorption/ionization quadrupole ion trap time-of-flight tandem mass
      spectrometry.
AB  - Plasmodium berghei strain NK65 is a rodent malaria parasite species widely used
      as a model of the human-infectious malaria parasite.  Because a rodent malaria
      parasite model allows issues to be addressed which would not be possible with
      human-infectious species, e.g., mode of action and in vivo screening, a
      convenient method to analyze the malaria parasite proteome is required.  The
      proteins of P. berghei separated using two-dimensional polyacrylamide gel
      electrophoresis were analyzed using matrix-assisted laser desorption/ionization
      quadrupole ion trap time-of-flight tandem mass spectrometry.

PMID- 22878639
TI  - Binding characteristics and dissociation kinetics for iron(II) complexes with
      seawater extractable organic matter and humic substances in a compost.
AB  - A steel-slag/compost fertilizer can be useful in supplying complex Fe(II) species
      to barren coastal regions. Seawater extractable organic matter (SWEOM) was
      examined for use as a novel chelator of Fe(II) in the compost. The dissociation
      kinetics for Fe(II)-SWEOM were evaluated, based on the rate of ligand-exchange
      with ortho-phenanthroline. The DeltaH(?) for the Fe(II)-SWEOM (19 kJ mol(-1)) was
      significantly smaller than the corresponding values for Fe(II) complexes with
      humic substances (27 kJ mol(-1)), suggesting that the Fe(II)-SWEOM is kinetically
      less stable.

PMID- 22878641
TI  - Retraction: Determination of protein-ligand interactions using accelerator mass
      spectrometry: modified crosslinking assay.

PMID- 22878640
TI  - Chromatographic separation studies of penicillins, cephalosporins and carbapenems
      on transition-metal silicate modified silica layers.
AB  - The chromatographic behavior of penicillins, cephalosporins and carbapenems has
      been studied on the thin layers of transition-metal ion (viz.
      Ni(2+)/Zn(2+)/Cu(2+)/Co(2+)) silicate modified silica. Transition-metal silicate
      (3.92%) and silica (96.08%) were found to be optimum and resulted in spherical
      compact spots and improved resolution of the analytes. The effect of various
      mobile phases was also investigated. The chromatograms were visualized as yellow
      spots by placing in an I(2)-chamber. The method has been found to be reproducible
      and convenient for routine analysis.

PMID- 22878642
TI  - Expression of a Trichoderma reesei beta-1,4 endo-xylanase in tall fescue modifies
      cell wall structure and digestibility and elicits pathogen defence responses.
AB  - An endo-xylanase from Trichoderma reesei (xyn2) has been expressed in tall fescue
      targeted to the vacuole, apoplast or Golgi, constitutively under the control of
      the rice actin promoter, and to the apoplast under the control of a senescence
      enhanced gene promoter. Constitutive xylanase expression in the vacuole,
      apoplast, and golgi, resulted in only a small number of plants with low enzyme
      activities and in reduced plant growth in apoplast, and golgi targeted plants.
      Constitutive expression in the apoplast also resulted in increased levels of cell
      wall bound hydroxycinnamic acid monomers and dimers, but no significant effect on
      cell wall xylose or arabinose content. In situ constitutive xylanase expression
      in the Golgi also resulted in increased ferulate dimers. However, senescence
      induced xylanase expression in the apoplast was considerably higher and did not
      affect plant growth or the level of monomeric hydroxycinnamic acids or lignin in
      the cell walls. These plants also showed increased levels of ferulate dimers, and
      decreased levels of xylose with increased levels of arabinose in their cell
      walls. While the release of cell wall hydroxycinnamic acids on self digestion was
      enhanced in these plants in the presence of exogenously applied ferulic acid
      esterase, changes in cell wall composition resulted in decreases in both tissue
      digestibility and cellulase mediated sugar release. In situ detection of H(2)O(2)
      production mediated by ethylene release in leaves of plants expressing apoplast
      xylanase could be leading to increased dimerisation. High-level xylanase
      expression in the apoplast also resulted in necrotic lesions on the leaves.
      Together these results indicate that xylanase expression in tall fescue may be
      triggering plant defence responses analogous to foliar pathogen attack mediated
      by ethylene and H(2)O(2).

PMID- 22878644
TI  - Quantitative mass spectrometry analysis reveals that deletion of the TRPV1
      receptor in mice alters substance P and neurokinin A expression in the central
      nervous system.
AB  - Vanilloid receptors have a central role in the processing of nociceptive stimuli.
      TRPV1 null mice showed significant decrease in response to heat noxious stimuli.
      However, thermal sensitivity is still present suggesting that the TRPV1 is not an
      exclusive transducer of thermal stimuli. Additionally, tachykinin peptides play a
      central role in pain processing and expression levels may also contribute in
      modifying the pain threshold. The LC-MS/MS analysis revealed that SP and NKA were
      significantly down-regulated in TRPV1(-/-) in spinal cord and brain tissues. In
      spinal cord, SP concentrations were 23.4 % lower (p < 0.0049) and NKA
      concentrations were 22.0 % lower (p < 0.0022) in TRPV1 null mice. Additionally,
      brain SP concentrations were 26.9 % lower (p < 0.0260) and brain NKA
      concentrations were 31.9 % lower (p < 0.0063) in TRPV1 null mice. These results
      clearly demonstrate that TPRV1 null mice exhibit lower SP and NKA concentrations
      in the central nervous system. The deficit of thermal responses may also be
      related to the down-regulations of SP and NKA.

PMID- 22878643
TI  - The adenosine A3 receptor agonist Cl-IB-MECA induces cell death through Ca2+/ROS
      dependent down regulation of ERK and Akt in A172 human glioma cells.
AB  - Adenosine A(3) receptor (A3AR) is coupled to G proteins that are involved in a
      variety of intracellular signaling pathways and physiological functions. 2-Chloro
      N(6)-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide (Cl-IB-MECA), an agonist of
      A3AR, has been reported to induce cell death in various cancer cells. However,
      the effect of CI-IB-MECA on glioma cell growth is not clear. This study was
      undertaken to examine the effect of CI-IB-MECA on glioma cell viability and to
      determine its molecular mechanism. CI-IB-MECA inhibited cell proliferation and
      induced cell death in a dose- and time-dependent manner. Treatment of CI-IB-MECA
      resulted in an increase in intracellular Ca(2+) followed by enhanced reactive
      oxygen species (ROS) generation. EGTA and N-acetylcysteine (NAC) blocked the cell
      death induced by CI-IB-MECA, suggesting that Ca(2+) and ROS are involved in the
      Cl-IB-MECA-induced cell death. Western blot analysis showed that CI-IB-MECA
      induced the down-regulation of extracellular signal-regulated kinases (ERK) and
      Akt, which was prevented by EGTA, NAC, and the A3AR antagonist MRS1191.
      Transfection of constitutively active forms of MEK, the upstream kinase of ERK,
      and Akt prevented the cell death. CI-IB-MECA induced caspase-3 activation and the
      CI-IB-MECA-induced cell death was blocked by the caspase inhibitors DEVD-CHO and
      z-VAD-FMK. In addition, expression of XIAP and Survivin were decreased in cells
      treated with Cl-IB-MECA. Collectively, these findings demonstrate that CI-IB-MECA
      induce a caspase-dependent cell death through suppression of ERK and Akt mediated
      by an increase in intracellular Ca(2+) and ROS generation in human glioma cells.
      These suggest that A3AR agonists may be a potential therapeutic agent for
      induction of apoptosis in human glioma cells.

PMID- 22878645
TI  - Significance of short chain fatty acid transport by members of the
      monocarboxylate transporter family (MCT).
AB  - Metabolism of short-chain fatty acids (SCFA) in the brain, particularly that of
      acetate, appears to occur mainly in astrocytes. The differential use has been
      attributed to transport, but the extent to which transmembrane movement of SCFA
      is mediated by transporters has not been investigated systematically. Here we
      tested the possible contribution of monocarboxylate transporters to SCFA uptake
      by measuring fluxes with labelled compounds and by following changes of the
      intracellular pH in Xenopus laevis oocytes expressing the isoforms MCT1, MCT2 or
      MCT4. All isoforms mediated significant transport of acetate. Formate, however,
      was transported only by MCT1. The contribution of MCT1 to SCFA transport was
      determined by using phloretin as a high-affinity inhibitor, which allowed a
      paired comparison of oocytes with and without active MCT1.

PMID- 22878646
TI  - Acute resveratrol treatment modulates multiple signaling pathways in the ischemic
      brain.
AB  - Resveratrol has several beneficial effects, including reductions of oxidative
      stress, inflammatory responses and apoptosis. It has been known that resveratrol
      is a sirtuin 1 (SIRT1) activator and protective effects of resveratrol are
      mediated by Akt and mitogen-activated protein kinases. However, it is not
      examined whether these pathways are regulated by resveratrol in the ischemic
      brain. Previously, we found that acute resveratrol treatment reduces brain injury
      induced by transient focal ischemic stroke. In the present study, we defined the
      signaling pathways modulated by resveratrol in ischemia by examining SIRT1
      expression and phosphorylation of Akt, ERK1/2 and p38 in the ischemic cortex.
      Resveratrol increased expression of SIRT1 and phosphorylation of Akt and p38 but
      inhibited the increase in phosphorylation of ERK1/2. Gene and protein levels of
      peroxisome proliferator-activated receptor gamma coactivator 1alpha, a downstream
      molecule of SIRT1, and mRNA levels of its target genes antioxidative superoxide
      dismutase 2 and uncoupling protein 2 were elevated. Resveratrol also increased
      phosphorylation of cyclic AMP-response-element-binding protein and transcription
      of the anti-apoptotic gene Bcl-2. These results suggest that various
      neuroprotective actions of resveratrol, including anti-oxidative, anti-apoptotic
      and inflammatory effects, are mediated via modulation of multiple signaling
      pathways in the ischemic brain.

PMID- 22878647
TI  - Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid
      oxidation parameters and clinical course in Alzheimer's disease.
AB  - Antioxidant vitamins are being widely discussed as a therapeutic option in
      Alzheimer's disease (AD). We recently found that supplementation with vitamin C
      and E over 1 month leads to an increase of their levels in cerebrospinal fluid
      (CSF) and a reduction of CSF lipid peroxidation. In the present study, we
      followed-up the biochemical and clinical effect of vitamin C and E
      supplementation in an open clinical trial over 1 year. Twelve AD patients stably
      taking a cholinesterase inhibitor were supplemented with vitamin C (1,000 mg/day)
      and E (400 I.U./day), while 11 patients taking cholinergic medication only served
      as a control group. Cognition was assessed at baseline, after 6 months and 12
      months using the Mini-Mental State Examination; a more detailed testing of
      cognitive function was performed at baseline and after 12 months. From eight of
      the vitamin-supplemented patients, CSF was taken at baseline, after 1 month and
      after 1 year to measure the antioxidant effect of vitamin supplementation on CSF
      lipids using a recently established in vitro oxidation assay. CSF antioxidant
      vitamins were significantly increased after 1 month and 1 year of
      supplementation, while in vitro oxidation of CSF lipids was significantly reduced
      only after 1 year of the supplementation. The clinical course of AD did not
      significantly differ between the vitamin and the control group. We conclude that
      supplementation with vitamins E and C did not have a significant effect on the
      course of AD over 1 year despite of a limited antioxidant effect that could be
      observed in CSF.

PMID- 22878648
TI  - EGFR-dependent downregulation of Capicua and the establishment of Drosophila
      dorsoventral polarity.
AB  - Dorsoventral (DV) axis formation in Drosophila begins during oogenesis through
      the graded activation of the EGF receptor (EGFR)-Ras-MAPK signaling pathway in
      the follicle cell layer of the egg chamber. EGFR signaling, which is higher in
      dorsal follicle cells, represses expression of the sulfotransferase-encoding gene
      pipe, thereby delimiting a ventral domain of Pipe activity that is critical for
      the subsequent induction of ventral embryonic fates. We have characterized the
      transcriptional circuit that links EGFR signaling to pipe repression: in dorsal
      follicle cells, the homeodomain transcription factor Mirror (Mirr), which is
      induced by EGFR signaling, directly represses pipe transcription, whereas in
      ventral follicle cells, the HMG-box protein Capicua (Cic) supports pipe
      expression by repressing mirr. Although Cic is under negative post
      transcriptional regulation by Ras-MAPK signaling in different contexts, the
      relevance of this mechanism for the interpretation of the EGFR signal during DV
      pattern formation remains unclear. Here, we consider a model where EGFR-mediated
      downregulation of Cic modulates the spatial distribution of Mirr protein in
      lateral follicle cells, thereby contributing to define the position at which the
      pipe expression border is formed.

PMID- 22878649
TI  - MicroRNA expression profiles associated with pancreatic adenocarcinoma and
      ampullary adenocarcinoma.
AB  - MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study
      was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded
      tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal
      pancreas and chronic pancreatitis without using micro-dissection and (2) to
      discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue.
      The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and
      107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay.
      Results were compared with chronic pancreatitis, normal pancreas and duodenal
      adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced
      expression in pancreatic cancer compared with normal pancreas. In all, 32
      microRNAs were differently expressed in pancreatic adenocarcinoma compared with
      chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not
      before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR
      622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently
      expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were
      correlated (0.990). MicroRNA expression profiles for pancreatic cancer described
      in the literature were consistent with our findings, and the microRNA profile for
      pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more
      significant expression profile, the difference between miR-411 and miR-198
      (P=2.06 * 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs
      (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also
      identified microRNA profiles to subclassify ampullary adenocarcinomas into
      pancreatobiliary or intestinal type. In conclusion, we found that combinations of
      two microRNAs could roughly separate neoplastic from non-neoplastic samples. A
      diagnostic 19 microRNA classifier was constructed which without micro-dissection
      could discriminate pancreatic and ampullary adenocarcinomas from chronic
      pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing
      prospective studies will evaluate if these microRNA profiles are useful on fine
      needle biopsies for early diagnosis of pancreatic cancer.

PMID- 22878650
TI  - Global mutational profiling of formalin-fixed human colon cancers from a
      pathology archive.
AB  - The advent of Next-Generation sequencing technologies, which significantly
      increases the throughput and reduces the cost of large-scale sequencing efforts,
      provides an unprecedented opportunity for discovery of novel gene mutations in
      human cancers. However, it remains a challenge to apply Next-Generation
      technologies to DNA extracted from formalin-fixed paraffin-embedded cancer
      specimens. We describe here the successful development of a custom DNA capture
      method using Next-Generation for detection of 140 driver genes in five formalin
      fixed paraffin-embedded human colon cancer samples using an improved extraction
      process to produce high-quality DNA. Isolated DNA was enriched for targeted exons
      and sequenced using the Illumina Next-Generation platform. An analytical pipeline
      using 3 software platforms to define single-nucleotide variants was used to
      evaluate the data output. Approximately 250 * average coverage was obtained with
      >96% of target bases having at least 30 sequence reads. Results were then
      compared with previously performed high-throughput Sanger sequencing. Using an
      algorithm of needing a positive call from all three callers to give a positive
      result, 98% of the verified Sanger sequencing somatic driver gene mutations were
      identified by our method with a specificity of 90%. In all, 13 insertions and
      deletions identified by Next-Generation were confirmed by Sanger sequencing. We
      also applied this technology to two components of a biphasic colon cancer, which
      had strikingly differing histology. Remarkably, no new driver gene mutation
      accumulation was identified in the more undifferentiated component. Applying this
      method to profiling of formalin-fixed paraffin-embedded colon cancer tissue
      samples yields equivalent sensitivity and specificity for mutation detection as
      Sanger sequencing of matched cell lines derived from these cancers. This method
      directly enables high-throughput comprehensive mutational profiling of colon
      cancer samples, and is easily extendable to enable targeted sequencing from
      formalin-fixed paraffin-embedded material for other tumor types.

PMID- 22878651
TI  - Prospective observational study of donor-site morbidity following anterior iliac
      crest bone-grafting in orthopaedic trauma reconstruction patients.
AB  - BACKGROUND: Complications associated with iliac crest bone-graft donor sites have
      been reported. This prospective study was conducted to determine the prevalence
      of pain and complications at the iliac crest donor site in patients undergoing
      treatment of fracture nonunion. METHODS: Ninety-two patients undergoing anterior
      iliac crest bone-grafting for nonunion or delayed union of a long-bone fracture
      were prospectively enrolled. Twenty-seven patients undergoing an alternative
      surgical treatment were enrolled as a control group. Questionnaires including
      pain on a visual analog scale (0 to 10) at the donor site were completed by
      patients at two weeks, six weeks, three months, and one year postoperatively.
      Short Form-36 (SF-36) forms were completed at enrollment and at the time of final
      follow-up. RESULTS: The mean pain on the visual analog scale at the donor site
      was 3.9 at two weeks but rapidly decreased to 1.4 at six weeks and reached 0.3 at
      one year or more postoperatively (p<0.001). Only two patients (2%) reported a
      pain value of >3 at one year or more postoperatively. There were three deep
      infections (3%) at the donor site, and no patients had a permanent sensory
      deficit in the lateral femoral cutaneous nerve distribution. At the time of final
      follow-up (mean, twenty-two months), scores for the SF-36 bodily pain subscale
      were significantly higher in the iliac crest group than in the control group,
      indicating a greater improvement in overall bodily pain in the iliac crest group.
      CONCLUSIONS: Anterior iliac crest bone-grafting for nonunion was a well-tolerated
      procedure. Substantial, persistent pain at the iliac crest donor site occurred in
      2% of patients. Iliac crest bone-grafting did not appear to impair function or
      well-being compared with alternative treatments.

PMID- 22878652
TI  - Patellofemoral instability.

PMID- 22878653
TI  - First-time patellar dislocation:  surgery or conservative treatment?
AB  - Primary patellar dislocation injures the medial patellofemoral ligament (MPFL),
      the major soft-tissue stabilizer of the patella, which may lead to recurrent
      patellar instability. Recurrent patellar dislocation are common and may require
      surgical intervention. The variation in location of injury of the MPFL and the
      presence of an osteochondral fracture produces challenges in clinical decision
      making between nonoperative and operative treatment, including the surgical
      modality, to repair or reconstruct the MPFL. Current evidence suggests that not
      all primary dislocations should undergo the same treatment. MPFL reconstruction
      may theoretically be more reliable than repair, but the optimal time to perform
      additional bony corrections is not known. A normal or minor dysplastic
      patellofemoral joint may be suitable for nonoperative treatment, whereas a higher
      grade of trochlear dysplasia or other significant abnormalities may benefit from
      surgical treatment. In this paper, we present a treatment algorithm for primary
      patellar dislocation.

PMID- 22878654
TI  - Rehabilitative protocols for select patellofemoral procedures and nonoperative
      management schemes.
AB  - There is a paucity of evidence-based care protocols for the management of
      patellofemoral (PF) joint conditions. There remains ambiguity in defining
      conditions; PF pain, malalignment, instability are intersecting patient cohorts
      in clinical practice. Treatment should address muscle strength deficits as well
      as movement pattern dysfunctions frequently observed in association with PF
      conditions. Quadriceps muscle dysfunction has significant heterogeneity in its
      etiology. The hip contributes to PF pathology as a consequence of femoral
      internal rotation and adduction. Inadequate gluteus medius ans maximus muscle
      performance is associated with kinematic flaws. Various surgical procedures are
      employed to address PF instability and associated pain patterns. Postoperative
      progressions should respect specific demands for bony healing, soft tissue
      healing and/or ligamentous graft incorporation. Symptomatic cartilage lesions may
      limit return to full function. Physical performance testing activities can be
      useful to measure patient progress and advise on return to activity/play.

PMID- 22878655
TI  - Imaging in patellofemoral instability: an abnormality-based approach.
AB  - Imaging in patellofemoral instability confirms the diagnosis and guides
      treatment. It is essential to the accurate diagnosis of the root causes and their
      adequate treatment. A structured approach must be used to identify the factors
      causing instability, and more than 1 imaging modality may provide similar
      information. This article revises the acute findings and the abnormalities
      present in the acute and the chronic settings.

PMID- 22878656
TI  - Distal realignment (tibial tuberosity transfer).
AB  - Although tibial tuberosity (TT) transfer has for many years been the basis of
      many protocols for the management of patellar instability, the role of pure
      medial transfer in particular appears to be declining. In contrast, the greater
      recognition of the importance of patella alta as a predisposing factor to
      recurrent patellar dislocation has resulted in a resurgence in the popularity of
      distal TT transfer. When TT transfer is performed, the direction and amount of
      transfer is based on the patellar height and the lateralization of the TT
      relative to the trochlear groove. Patellar height is best assessed on a lateral
      radiograph with the knee in flexion using a ratio that uses the articular surface
      of the patella in relation to the height above the tibia. Assessment of
      lateralization of the TT relative to the trochlear groove can be made using
      either computed tomography or magnetic resonance imaging scans.

PMID- 22878657
TI  - Medial patellofemoral ligament reconstruction:  indications and technique.
AB  - Lateral instability of the patella is a common problem that often requires
      reconstruction of the proximal soft tissue restraints. The medial patellofemoral
      ligament (MPFL) has been demonstrated to be the major soft tissue stabilizer to
      prevent abnormal lateral displacement of the patella. In this chapter we will
      discuss the anatomy, biomechanics, indications, and technique for surgical
      reconstruction of the medial patellofemoral ligament.

PMID- 22878658
TI  - The role of trochleoplasty in patellofemoral instability.
AB  - The management of recurrent patellofemoral instability is challenging. The
      etiology of the instability is multifactorial, requiring the examination of lower
      limb alignment, relationship of the patella to the trochlear groove and tibial
      tubercle, and the soft-tissue restraints. As initial surgical efforts were aimed
      at isolated soft-tissue repair or reconstruction, patients often had continued
      instability. Thus, a heightened interest in trochleoplasty has occurred as
      trochlear dysplasia has been found in 85% of patients with recurrent instability.
      Different types of trochleoplasties have been developed depending on the type of
      dysplasia including the trochlear lengthening osteotomy, the proximal open
      trochleoplasty, the deepening trochleoplasty, and the arthroscopic deepening
      trochleoplasty. The techniques, benefits, and results of these trochleoplasties
      will be presented in this review.

PMID- 22878659
TI  - Cartilage lesions in patellofemoral dislocations:  incidents/locations/when to
      treat.
AB  - Patellofemoral (PF) dislocations are frequently associated with chondral injury.
      Chondral and osteochondral lesions are often associated with traumatic (high
      energy) PF dislocations, whereas atraumatic (low-energy) PF dislocations in
      patients with significant PF risk factors have a much lower incidence of
      osteochondral damage. This article provides a historical overview and delineates
      the current state of radiographic and clinical outcomes of osteochondral lesions
      after PF dislocation. The importance of understanding risk factors of
      redislocation is emphasized, and the current treatment options for these
      cartilage lesions associated with PF dislocation are briefly summarized.

PMID- 22878660
TI  - Complications in patellofemoral surgery.
AB  - The complexity of patellofemoral morphology, combined with its injuries and
      degenerative patterns, leads to varied pathologic diagnoses, as well as surgical
      procedures to address these problems. Surgical procedures in the patellofemoral
      joint include tibial tubercle osteotomy, medial patellofemoral ligament surgery,
      soft tissue procedures on the lateral aspect of the patella, trochleoplasty, and
      patellofemoral arthroplasty. Understanding potential complications related to the
      various surgical procedures in the patellofemoral joint is critical to successful
      surgery. The purpose of this article is to discuss potential surgical
      complications in procedures performed to address patellofemoral pathology and
      describe ways to avoid these pitfalls.

PMID- 22878661
TI  - Endoscopic endonasal resection of sinonasal and skull base malignancies in
      children: feasibility and outcomes.
AB  - BACKGROUND: The aim of this study is to present our experience in treating
      paediatric sinonasal and skull base malignancies with exclusively endonasal
      endoscopic approach and measure its feasibility. METHODS: This study is a
      retrospective review of seven patients under age of 19 years who have sinonasal
      and skull base malignancies and treated with endoscopic endonasal approach. The
      main outcome measures are the surgical resection, complications, survival rate,
      recurrence and gross facial growth. RESULTS: Radical tumour resection was
      achieved in all cases with negative margins; no major complications were
      observed. Mean follow-up was 65 months and no evidence of recurrences. Facial
      growth assessment showed no gross changes. CONCLUSION: In selected cases,
      endoscopic endonasal approach of paediatric sinonasal and skull base malignancies
      could be an alternative approach. Despite of our few cases, it showed a
      feasibility of this technique with satisfactory oncological control. A further
      collaborative study with larger number is needed to have more valid conclusion.

PMID- 22878662
TI  - Awareness of spina bifida and periconceptional use of folic acid among pregnant
      women in a developing economy.
AB  - BACKGROUND: Folate deficiency in pregnant women is a recognized cause of spina
      bifida. We sought to establish the level of awareness of spina bifida as well as
      the use of folate supplementation among pregnant women in a developing economy.
      METHOD: Interviewer-administered questionnaires were used to obtain information
      from 200 to 20 randomly selected pregnant women attending antenatal clinics at
      the authors' institution. Demographic information and information on parity,
      folic acid use and knowledge on spina bifida including its cause, prevention and
      treatment were obtained. Data analyses were done using Epi Info version 6.
      RESULTS: The mean age of the women was 30.3 years (range 17-52 years). Sixty-six
      of the women (30.0 %) were primigravida. Most of the respondents [208 (94.5 %)]
      have attained, at least, secondary level of education. The average gestational
      age at antenatal clinic booking was 20.7 weeks (range 4-38 weeks), while the
      average gestational age at commencement of folic acid use was 18.5 weeks (range 4
      38 weeks). None of them used folic acid in the preconception period. Knowledge
      about spina bifida is poor and a significant number [103 (46.8 %)] have
      superstitious belief about its aetiology. Only 56 (25.5 %) of the respondents are
      aware that folic acid use prevents its occurrence; however, 194 (88.2 %) are
      willing to receive periconceptional folate supplementation. CONCLUSION: There is
      paucity of knowledge about spina bifida among Nigerian pregnant women despite
      their high level of formal education. We advocate an aggressive public health
      campaign to enlighten the women about spina bifida and encourage periconceptional
      folate supplementation.

PMID- 22878663
TI  - FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease
      duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS
      mutation.
AB  - Basophilic inclusions (BIs) are pathological features of a subset of
      frontotemporal lobar degeneration disorders, including sporadic amyotrophic
      lateral sclerosis (ALS) and familial ALS (FALS). Mutations in the fused in
      sarcoma/translocated in liposarcoma (FUS/TLS) gene have recently been identified
      as a cause of FALS. The FUS/TLS-immunoreactive inclusions are consistently found
      in cases of frontotemporal lobar degeneration with BIs; however, the association
      between ALS cases with BIs and FUS/TLS accumulation is not well understood. We
      used immunohistochemistry to analyze 3 autopsy cases of FALS with the FUS/TLS
      mutation and with BIs using anti-FUS/TLS antibodies. The disease durations were
      1, 3, and 9 years. As the disease duration becomes longer, there were broader
      distributions of neuronal and glial FUS/TLS-immunoreactive inclusions. As early
      as 1 year after the onset, BIs, neuronal cytoplasmic inclusions and glial
      cytoplasmic inclusions were found in the substantia nigra in addition to the
      anterior horn of the spinal cord. Glial cytoplasmic inclusions are found earlier
      and in a wider distribution than neuronal cytoplasmic inclusions. The
      distribution of FUS/TLS-immunoreactive inclusions in FUS/TLS-mutated FALS with
      BIs was broader than that of BIs alone, suggesting that the pathogenetic
      mechanism may have originated from the FUS/TLS proteinopathy.

PMID- 22878664
TI  - Gadolinium- and 5-aminolevulinic acid-induced protoporphyrin IX levels in human
      gliomas: an ex vivo quantitative study to correlate protoporphyrin IX levels and
      blood-brain barrier breakdown.
AB  - In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX)
      fluorescence guidance has been used as a surgical adjunct to improve the extent
      of resection of gliomas. Exogenous administration of ALA before surgery leads to
      the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can
      visualize and thereby discriminate between normal and tumor tissue. Selective
      accumulation of PpIX has been linked to numerous factors, of which blood-brain
      barrier breakdown has been suggested to be a key factor. To test the hypothesis
      that PpIX concentration positively correlates with gadolinium (Gd)
      concentrations, we performed ex vivo measurements of PpIX and of Gd using
      inductively coupled plasma mass spectrometry, the latter as a quantitative
      biomarker of blood-brain barrier breakdown; this was corroborated with
      immunohistochemistry of microvascular density in surgical biopsies of patients
      undergoing fluorescence-guided surgery for glioma. We found positive correlations
      between PpIX concentration and Gd concentration (r = 0.58, p < 0.0001) and
      between PpIX concentration and microvascular density (r = 0.55, p < 0.0001),
      suggesting a significant, yet limited, association between blood-brain barrier
      breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first
      time that Gd measurements by inductively coupled plasma mass spectrometry have
      been used in human gliomas.

PMID- 22878665
TI  - Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of
      patients with mesial temporal lobe epilepsy.
AB  - Recent experimental data in mice have shown that the inwardly rectifying K
      channel Kir4.1 mediates K spatial buffering in the hippocampus. Here we used
      immunohistochemistry to examine the distribution of Kir4.1 in hippocampi from
      patients with medication-refractory temporal lobe epilepsy. The selectivity of
      the antibody was confirmed in mice with a glial conditional deletion of the gene
      encoding Kir4.1. These mice showed a complete loss of labeled cells, indicating
      that Kir4.1 is restricted to glia. In human cases, Kir4.1 immunoreactivity
      observed in cells morphologically consistent with astrocytes was significantly
      reduced in 12 patients with hippocampal sclerosis versus 11 patients without
      sclerosis and 4 normal autopsy controls. Loss of astrocytic Kir4.1
      immunoreactivity was most pronounced around vessels and was restricted to gliotic
      areas. Loss of Kir4.1 expression was associated with loss of dystrophin and alpha
      syntrophin, but not with loss of beta-dystroglycan, suggesting partial disruption
      of the dystrophin-associated protein complex. The changes identified in patients
      with hippocampal sclerosis likely interfere with K homeostasis and may contribute
      to the epileptogenicity of the sclerotic hippocampus.

PMID- 22878666
TI  - IgG leakage may contribute to neuronal dysfunction in drug-refractory epilepsies
      with blood-brain barrier disruption.
AB  - Focal epilepsies are often associated with blood-brain barrier disruption. In 4
      entorhinal cortex tissue samples and 13 hippocampal samples from patients with
      pharmacoresistent temporal lobe epilepsy, we observed immunoglobulin G (IgG)
      leakage in the parenchyma and IgG-positive neurons that had evidence of
      neurodegeneration, such as shrinkage and eosinophilia. These findings were not
      present in samples from 12 nonepileptic control subjects. To complement these
      findings, we used a rat in vivo model that mimics the development of limbic
      epilepsy with blood-brain barrier disruption. During epileptogenesis, IgG leakage
      and neuronal IgG uptake increased concomitantly with the occurrence of seizures.
      Immunoglobulin G accumulation in neurons was selective, particularly for
      interneurons and pyramidal neurons. Immunohistochemistry and electron microscopy
      showed that IgG uptake in the rat neurons was associated with eosinophilia,
      shrinkage, and ultrastructural degenerative changes. Moreover, IgG-positive
      neurons lost their NeuN immunohistochemical staining. Together, these
      observations suggest that IgG leakage is related to neuronal impairment and may
      be a pathogenic mechanism in epileptogenesis and chronic epilepsy.

PMID- 22878667
TI  - Management of glucocorticoid-induced osteoporosis.
AB  - This review summarizes the available evidence-based data that form the basis for
      therapeutic intervention and covers the current status of glucocorticoid-induced
      osteoporosis (GIOP) management, regulatory requirements, and risk-assessment
      options. Glucocorticoids are known to cause bone loss and fractures, yet many
      patients receiving or initiating glucocorticoid therapy are not appropriately
      evaluated and treated. An European Society for Clinical and Economic Aspects of
      Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management
      and to provide a report by a panel of experts. An expert panel reviewed the
      available studies that discussed approved therapeutic agents, focusing on
      randomized and controlled clinical trials reporting on bone mineral density
      and/or fracture risk of at least 48 weeks' duration. There is no evidence that
      GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX
      algorithm can be adjusted according to glucocorticoid dose. Available
      antiosteoporotic therapies such as bisphosphonates and teriparatide are
      efficacious in GIOP management. Several other agents approved for the treatment
      of postmenopausal osteoporosis may become available for GIOP. It is advised to
      stop antiosteoporotic treatment after glucocorticoid cessation, unless the
      patient remains at increased risk of fracture. Calcium and vitamin D
      supplementation as an osteoporosis-prevention measure is less effective than
      specific antiosteoporotic treatment. Fracture end-point studies and additional
      studies investigating specific subpopulations (pediatric, premenopausal, or
      elderly patients) would strengthen the evidence base and facilitate the
      development of intervention thresholds and treatment guidelines.

PMID- 22878668
TI  - Application of an intracellular stability test of a novel missense menin mutant
      to the diagnosis of multiple endocrine neoplasia type 1.
AB  - Germline MEN1 mutation analysis is a powerful tool for an early diagnosis of
      multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant familial cancer
      syndrome characterized by the parathyroid, pituitary and gastroenteropancreatic
      endocrine tumors.  However, the clinical significance of MEN1 gene variants,
      especially missense and in-frame mutations as well as some splicing mutations, is
      not always obvious.  We have previously shown that mutant menin proteins
      associated with MEN1 are rapidly degraded by the ubiquitin-proteasome pathway. 
      We also demonstrated by a fluorescent immunocytochemical stability test that the
      stability of missense and in-frame deletion mutants varies widely but that
      unstable mutants were found only in MEN1 and related disorders and not in normal
      polymorphisms.  In the present study, we evaluated by this stability test the
      pathogenicity of a novel MEN1 missense mutation, c.1118C>T, encoding a P373L
      mutant menin, identified in a suspected MEN1 patient.  The results demonstrated
      that the mutant menin is highly unstable, indicating that this mutation is
      causative for MEN1.  These findings encouraged us to proceed with presymptomatic
      genetic screening for this mutation among the family members, which resulted in
      the identification of asymptomatic mutation carriers.  Thus, the information from
      the menin stability test was useful for genetic diagnosis and counseling of MEN1
      in the case with a previously unreported MEN1 missense mutation.

PMID- 22878669
TI  - Adipose tissue inflammation and ectopic lipid accumulation.
AB  - Obesity may be viewed as a chronic low-grade inflammatory disease as well as a
      metabolic disease.  Indeed, unbalanced production of pro- and anti-inflammatory
      adipocytokines critically contributes to the obesity-induced insulin resistance. 
      In addition to lipid-laden mature adipocytes, adipose tissue is composed of
      various stromal cells such as preadipocytes, endothelial cells, fibroblasts, and
      immune cells that may be involved in adipose tissue functions.  Accumulating
      evidence has suggested that adipocytes and stromal cells in adipose tissue change
      dramatically in number and cell type during the course of obesity, which is
      referred to as "adipose tissue remodeling."  Among stromal cells, infiltration of
      macrophages in obese adipose tissue precedes the development of insulin
      resistance in animal models, suggesting that they are crucial for adipose tissue
      inflammation.  We have provided evidence suggesting that a paracrine loop
      involving saturated fatty acids and tumor necrosis factor-alpha derived from
      adipocytes and macrophages, respectively, aggravates obesity-induced adipose
      tissue inflammation.  On the other hand, storing excessive energy as triglyceride
      is also a fundamental function of adipose tissue.  Recent evidence suggests that
      reduced lipid storage in obese adipose tissue contributes to ectopic lipid
      accumulation in non-adipose tissues such as the liver, skeletal muscle, and
      pancreas, where lipotoxicity impairs their metabolic functions.  Notably, chronic
      inflammation is capable of inducing insulin resistance, lipolysis, and
      interstitial fibrosis in adipose tissue, all of which may reduce the lipid
      storing function.  Understanding the molecular mechanism underlying adipose
      tissue remodeling may lead to the identification of novel therapeutic strategies
      to prevent or treat obesity-induced adipose tissue inflammation.

PMID- 22878670
TI  - Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet
      allograft survival.
AB  - Costimulation blockade is an effective way to prevent allograft rejection. In
      this study, we tested the efficacy of two negative co-signaling molecules in
      protecting islet allograft function. We used local expression of B7-H4 by
      adenoviral transduction of islets (Ad-B7-H4) and systemic administration of CTLA
      4.Ig to investigate the outcomes of allograft survival. Five groups of
      streptozotocin-induced diabetic C57BL/6 mice received 400 islets each from BALB/c
      donors. The groups consisted of control (G1); CTLA-4.Ig (G2); Ad-LacZ (G3); Ad-B7
      H4 (G4); and Ad-B7-H4 and CTLA-4.Ig combined (G5). G1 and G3 developed graft
      failure on average of two weeks. G2, G4 and G5 survived for 43.8 +/- 34.8, 54.7
      +/- 31.2 and 77.8 +/- 21.5 d, respectively. Activated T and B cells in the lymph
      nodes were significantly controlled by CTLA-4.Ig treatment. Significantly reduced
      infiltrates were also detected in the allografts of G2 compared with G1. By
      contrast, B7-H4 significantly inhibited Th1-associated IFN-gamma secretion in the
      early stage and increased Foxp3 (+)  T cells in the long-term surviving
      allografts. Our study suggests that CTLA-4 and B7-H4 inhibit alloimmune responses
      through distinct mechanisms, and that combination therapy which activates two
      negative co-signaling pathways can further enhance islet allograft survival.

PMID- 22878672
TI  - Indications for and surgical complications of rotationplasty.
AB  - BACKGROUND: Rotationplasty is one treatment option for femoral bone sarcomas in
      skeletally immature patients. This procedure can also be used to save failed limb
      salvage procedures such as infected prostheses and failed bone grafts in adults.
      Rotationplasty is only rarely indicated, and the surgical complications and risk
      factors for failure of the procedure that might influence the treatment or
      patient choices have not been well described. METHODS: We retrospectively
      reviewed 19 patients who underwent rotationplasty focusing on surgical
      indications, surgical procedures such as the type of rotationplasty, and whether
      vessels were sacrificed and reconstructed with vascular anastomosis or preserved.
      Risk factors for failure of rotationplasty were categorized into either early or
      late postoperative complications. RESULTS: Thirteen of 19 rotationplasties were
      done for patients diagnosed with primary sarcoma, 3 patients for unplanned
      excisions of sarcomas, and 3 patients for infection. Two of 19 patients did not
      have sufficient circulation resulting in amputation. Six of 19 patients underwent
      vascular anastomoses, and all of these anastomoses were successful. Three
      patients had multiple operations for infection before rotationplasty, and one
      patient's treatment failed so an amputation was required. As late complications,
      one patient had delayed bone union and one had postoperative infection that
      healed after removal of plate fixation. Two patients had malrotation of the tibia
      that resolved with revision surgery. One patient had a skin ulcer that healed
      with conservative treatment. One patient who had an unplanned excision had a
      hemipelvectomy for non-union 11 months after rotationplasty. CONCLUSIONS:
      Rotationplasty was successfully accomplished in 16 of the 19 patients (84 %) with
      sarcomas, unplanned excision of sarcomas or infection. Vascular anastomosis did
      not increase the risk of rotationplasty failure in our series. Patients appeared
      to have a higher risk of failure of rotationplasty after multiple operations,
      possibly because of inflammation around the vessels. The surgeon should be aware
      of the higher potential risk and consider vascular anastomosis for these
      patients.

PMID- 22878671
TI  - Perioperative complications of anterior cervical decompression with fusion in
      patients with ossification of the posterior longitudinal ligament: a
      retrospective, multi-institutional study.
AB  - BACKGROUND: Anterior decompression with fusion (ADF) for patients with cervical
      ossification of the posterior longitudinal ligament (OPLL) is reportedly
      associated with a higher incidence of complications than is laminoplasty.
      However, the frequency of perioperative complications associated with ADF for
      cervical OPLL has not been fully established. The purpose of this study was to
      investigate the incidence of perioperative complications, especially neurological
      complications, following ADF performed to relieve compressive cervical myelopathy
      due to cervical OPLL. METHODS: Study participants comprised 150 patients who had
      undergone ADF for cervical OPLL at 27 institutions between 2005 and 2008.
      Perioperative--especially neurological--complications occurring within 2 weeks
      after ADF were analyzed. Preoperative imaging findings, including Cobb angle,
      between C2 and C7 and occupying ratio of OPLL were investigated. Multivariate
      analysis with logistic regression was performed to identify independent risk
      factors for neurological complications. RESULT: Three patients (2.0 %) showed
      deterioration of lower-extremity function after ADF. One of the three patients
      had not regained their preoperative level of function 6 months after surgery.
      Upper-extremity paresis occurred in 20 patients (13.3 %), five of whom had not
      returned to preoperative levels 6 months after surgery. Patients with upper
      extremity paresis showed significantly higher occupying ratios of OPLL, greater
      blood loss, longer operation times, fusion of more segments, and higher rates of
      cerebrospinal fluid leakage than those without paresis. Independent risk factors
      for upper-extremity paresis were a high occupying ratio of OPLL and large blood
      loss during surgery. CONCLUSIONS: The incidences of deterioration in upper- and
      lower-extremity functions were 13.3 % and 2.0 %, respectively. Patients with a
      high occupying ratio of OPLL are at higher risk of developing neurological
      deterioration.

PMID- 22878673
TI  - The safest direction of percutaneous pinning for achieving firm fixing of the
      fifth carpometacarpal joint.
AB  - INTRODUCTION: Traditional treatment of unstable fifth carpometacarpal joint
      injuries is closed reduction and pinning. The purpose of this study was to
      determine the safest corridor for pinning of the fifth carpometacarpal joint to
      prevent iatrogenic injury to the ulnar nerve and tendons. MATERIALS AND METHODS:
      In the first phase of study, three fresh cadavers were dissected and the safest
      directions of Kirschner wire (k-wire) insertion in the coronal and sagittal
      planes were determined for k-wire entrance 2 cm distal to the base of the fifth
      metacarpal. The second phase objective was to evaluate the accuracy of data
      obtained in the previous phase. Therefore, with five other cadavers, k-wires were
      inserted in a combination of maximum angles in different planes determined
      previously. The ulnar nerve branches and tendons were then investigate to detect
      possible damage. In the third phase, four fresh carpometacarpal joints were fixed
      with directions outside the range of the defined angles. RESULTS: The safe
      direction determined in the first phase was a 20 degrees -30 degrees  coronal
      plane angle relative to the body of the fifth metacarpal bone and between 10
      degrees  volar to dorsal to 20 degrees  dorsal to volar angle in the sagittal
      plane. Insertion of k-wires in the second phase could fix the fifth
      carpometacarpal joint firmly without penetration of the volar and dorsal cortices
      of the hamate. All inserted k-wires outside the defined range resulted in
      injuries to nerves or tendons or loose fixing. CONCLUSION: The safest corridor
      for pinning unstable fifth carpometacarpal injuries is 2 cm distal to the joint
      at an angle of 20 degrees -30 degrees  to the coronal plane from 10 degrees 
      volar to dorsal to 20 degrees  dorsal to volar direction in the sagittal plane.

PMID- 22878674
TI  - A study of epileptogenic network structures in rat hippocampal cultures using
      first spike latencies during synchronization events.
AB  - Study of hypersynchronous activity is of prime importance for combating epilepsy.
      Studies on network structure typically reconstruct the network by measuring
      various aspects of the interaction between neurons and subsequently measure the
      properties of the reconstructed network. In sub-sampled networks such methods
      lead to significant errors in reconstruction. Using rat hippocampal neurons
      cultured on a multi-electrode array dish and a glutamate injury model of epilepsy
      in vitro, we studied synchronous activity in neuronal networks. Using the first
      spike latencies in various neurons during a network burst, we extract various
      recurring spatio-temporal onset patterns in the networks. Comparing the patterns
      seen in control and injured networks, we observe that injured networks express a
      wide diversity in their foci (origin) and activation pattern, while control
      networks show limited diversity. Furthermore, we note that onset patterns in
      glutamate injured networks show a positive correlation between synchronization
      delay and physical distance between neurons, while control networks do not.

PMID- 22878675
TI  - [The group of disorders of somatoform disorders: old and new challenges].

PMID- 22878676
TI  - [Repetitive impulse-associated behavioral disorders in Parkinson's disease].
AB  - Parkinson's disease (PD) is associated with a number of behavioral disorders
      which may cause considerable social, professional or financial problems. Impulse
      control disorders (ICDs), such as pathological gambling, binge eating, compulsive
      shopping and hypersexuality occur in approximately 13-14% of PD patients. Further
      behavioral disorders are the dopamine dysregulation syndrome (DDS), a substance
      dependence characterized by craving for dopaminergic substances and punding
      (prolonged repetitive activities which are not goal-oriented).Treatment-related
      risk factors are dopamine agonists for ICDs and a high total dopaminergic dose
      for DDS and punding. Shared risk factors are young age at onset, impulsive
      personality traits, depression and possibly dyskinesia. At the neuronal level
      these behavioral disorders seem to be associated with changes in the reward
      system and dysfunction of the orbitofrontal cortex. The evidence level for
      management strategies is at present insufficient. For ICDs current clinical
      practice consists of discontinuation or reduction of dopamine agonists.

PMID- 22878677
TI  - Distinct pathophysiologic mechanisms of septic acute kidney injury: role of
      immune suppression and renal tubular cell apoptosis in murine model of septic
      acute kidney injury.
AB  - OBJECTIVE: Sepsis is the most common cause of acute kidney injury in critically
      ill patients; however, the mechanisms leading to acute kidney injury in sepsis
      remain elusive. Although sepsis has been considered an excessive systemic
      inflammatory response, clinical trials that inhibit inflammation have been shown
      to have no effect. The purpose of this study was to examine the pathophysiology
      of septic acute kidney injury focusing on immune responses and renal tubular cell
      apoptosis by providing an on-site quantitative comparison between septic- and
      ischemia/reperfusion-induced acute kidney injury. DESIGN: Twenty-four hours after
      cecal ligation and puncture or ischemia/reperfusion injury, biochemical,
      histologic, and cytokine changes were compared in C57BL/6 mice. Apoptosis was
      assessed, and the effect of caspase 3 inhibition on renal function was also
      examined. The percentage of regulatory T cells and the effect of depletion were
      determined and compared with ischemia/reperfusion-induced acute kidney injury.
      The effect of interleukin-10 blocking was also compared. MEASUREMENTS AND MAIN
      RESULTS: Despite comparable renal dysfunction, acute tubular necrosis or
      inflammation was minimal in septic kidneys. However, tubular cell apoptosis was
      prominent, and caspase 3 activity was positively correlated with renal
      dysfunction. A decrease in apoptosis by caspase 3 inhibitor resulted in
      attenuation of renal dysfunction. In assessment of systemic immunity, septic
      acute kidney injury was associated with an increase in interleukin-10, and also
      showed massive immune cell apoptosis with increased regulatory T cells. In
      contrast to ischemia/reperfusion injury in which depletion of regulatory T cells
      aggravated renal injury, depletion of regulatory T cells before cecal ligation
      and puncture resulted in renoprotection. In addition, blocking interleukin-10
      rescued septic mice from the development of acute kidney injury, whereas it had
      no effect in ischemia/reperfusion injury. CONCLUSIONS: Pathogenesis of septic
      acute kidney injury is thought to be different from that of ischemia/reperfusion
      induced acute kidney injury. Our data showed a link between apoptosis, immune
      suppression, and the development of acute kidney injury during sepsis and suggest
      that strategies targeting apoptosis or enhancing immunity might be a potential
      therapeutic strategy for septic acute kidney injury.

PMID- 22878678
TI  - Initial resuscitation guided by the Surviving Sepsis Campaign recommendations and
      early echocardiographic assessment of hemodynamics in intensive care unit septic
      patients: a pilot study.
AB  - OBJECTIVE: To compare therapeutic interventions during initial resuscitation
      derived from echocardiographic assessment of hemodynamics and from the Surviving
      Sepsis Campaign guidelines in intensive care unit septic patients. DESIGN AND
      SETTING: Prospective, descriptive study in two intensive care units of teaching
      hospitals. METHODS: The number of ventilated patients with septic shock who were
      studied was 46. Transesophageal echocardiography was first performed (T1<3 hrs
      after intensive care unit admission) to adapt therapy according to the following
      predefined hemodynamic profiles: fluid loading (index of collapsibility of the
      superior vena cava>=36%), inotropic support (left ventricular fractional area
      change<45% without relevant index of collapsibility of the superior vena cava),
      or increased vasopressor support (right ventricular systolic dysfunction,
      unremarkable transesophageal echocardiography study consistent with sustained
      vasoplegia). Agreement for treatment decision between transesophageal
      echocardiography and Surviving Sepsis Campaign guidelines was evaluated. A second
      transesophageal echocardiography assessment (T2) was performed to validate
      therapeutic interventions. RESULTS: Although transesophageal echocardiography and
      Surviving Sepsis Campaign approaches were concordant to manage fluid loading in
      32 of 46 patients (70%), echocardiography led to the absence of blood volume
      expansion in the remaining 14 patients who all had a central venous pressure<12
      mm Hg. Accordingly, the agreement was weak between transesophageal
      echocardiography and Surviving Sepsis Campaign for the decision of fluid loading
      (kappa: 0.37 [0.16;0.59]). With a cut-off value<8 mm Hg for central venous
      pressure, kappa was 0.33 [-0.03;0.69]. Inotropes were prescribed based on
      transesophageal echocardiography assessment in 14 patients but would have been
      decided in only four patients according to Surviving Sepsis Campaign guidelines.
      As a result, the agreement between the two approaches for the decision of
      inotropic support was weak (kappa: 0.23 [-0.04;0.50]). No right ventricular
      dysfunction was observed. No patient had anemia and only three patients with
      transesophageal echocardiography documented left ventricular systolic dysfunction
      had a central venous oxygen saturation<70%. CONCLUSIONS: A weak agreement was
      found in the prescription of fluid loading and inotropic support derived from
      early transesophageal echocardiography assessment of hemodynamics and Surviving
      Sepsis Campaign guidelines in patients presenting with septic shock.

PMID- 22878679
TI  - Lung microenvironment contributes to the resistance of alveolar macrophages to
      develop tolerance to endotoxin*.
AB  - OBJECTIVE: Endotoxin tolerance corresponds to reprogramming of mononuclear
      phagocytes after iterative encounters with toll-like receptor agonists aimed to
      dampen the inflammatory response. We investigated why this phenomenon cannot be
      observed with murine alveolar macrophages. DESIGN: Animal study. SETTING:
      Research institution laboratory. SUBJECTS: rag2-/-, rag2gammac-/-, cd3epsilon-/-,
      u-/-, il-15-/-, Jalpha18-/-, ifngammar-/-, il-18r-/-, and wild-type mice.
      INTERVENTIONS: Alveolar macrophages were harvested from untreated mice or after
      injection of endotoxin. Alveolar macrophages were activated in vitro with
      endotoxin (lipopolysaccharide), and tumor necrosis factor production was
      monitored. MEASUREMENTS AND MAIN RESULTS: In contrast to monocytes or peritoneal
      macrophages, alveolar macrophages did not display endotoxin tolerance in an ex
      vivo model after injection of endotoxin. An in vivo systemic inhibition of
      granulocyte-macrophage colony-stimulating factor or interferon-gamma allowed the
      induction of alveolar macrophage endotoxin tolerance, which was also observed in
      interferon-gamma receptor-deficient mice. Using mice missing different leukocyte
      subsets and adoptive cell transfers, we demonstrated the involvement of B
      lymphocytes in interferon-gamma production within the lung microenvironment and
      in the prevention of alveolar macrophage endotoxin tolerance. Furthermore, we
      demonstrated the importance of interleukin-18 in preventing alveolar macrophage
      endotoxin tolerance through studies of interleukin-18 messenger RNA expression in
      il-18r-/- mice and injection of interleukin-18 in rag2-/- and u-/- mice.
      CONCLUSIONS: Our results support the conclusion that at homeostasis in the lungs,
      constitutive expression of granulocyte-macrophage colony-stimulating factor,
      interleukin-18, interferon-gamma and possibly interleukin-15, and a cross-talk
      between B lymphocytes and alveolar macrophages create a microenvironment specific
      to the lungs that prevents alveolar macrophages from becoming tolerant to
      endotoxin.

PMID- 22878680
TI  - Nanoparticle deposition onto biofilms.
AB  - We develop a mathematical model of nanoparticles depositing onto and penetrating
      into a biofilm grown in a parallel-plate flow cell. We carry out deposition
      experiments in a flow cell to support the modeling. The modeling and the
      experiments are motivated by the potential use of polymer nanoparticles as part
      of a treatment strategy for killing biofilms infecting the deep passages in the
      lungs. In the experiments and model, a fluid carrying polymer nanoparticles is
      injected into a parallel-plate flow cell in which a biofilm has grown over the
      bottom plate. The model consists of a system of transport equations describing
      the deposition and diffusion of nanoparticles. Standard asymptotic techniques
      that exploit the aspect ratio of the flow cell are applied to reduce the model to
      two coupled partial differential equations. We perform numerical simulations
      using the reduced model. We compare the experimental observations with the
      simulation results to estimate the nanoparticle sticking coefficient and the
      diffusion coefficient of the nanoparticles in the biofilm. The distributions of
      nanoparticles through the thickness of the biofilm are consistent with diffusive
      transport, and uniform distributions through the thickness are achieved in about
      four hours. Nanoparticle deposition does not appear to be strongly influenced by
      the flow rate in the cell for the low flow rates considered.

PMID- 22878681
TI  - Nine-week trastuzumab treatment versus 52-week trastuzumab treatment for HER2
      positive early-stage breast cancer.
AB  - PURPOSES: Trastuzumab is known to be effective for early and advanced stages of
      breast cancer but optimal duration for early-stage breast cancer (EBC) is not
      well known. We evaluated the efficacy and toxicity of 9- and 52-week trastuzumab
      therapy for EBC retrospectively. METHODS: In this multicenter study, the medical
      records of all patients with EBC were analyzed in 8 centers retrospectively.
      Totally consecutive, 479 female patients who received trastuzumab in the adjuvant
      treatment were evaluated for disease-free survival (DFS), overall survival (OS),
      efficacy, and toxicity. RESULTS: There were 181 (37.8 %) and 298 (62.2 %)
      patients in the 9- and 52-week trastuzumab groups, respectively. Median follow-up
      was 30.6 months (5.7-68.9) in the 9-week trastuzumab group and 29.3 months (5.9
      59.6) in the 52-week trastuzumab group. Thirty-six month DFS was 90 and 85 % (P =
      0.132) in the 9- and 52-week trastuzumab treatment groups, respectively, and 36
      month OS was 96 and 97 % in the 9- and 52-week trastuzumab groups, respectively
      (P = 0.779). Symptomatic cardiotoxicity was observed in 1 (0.6 %) patient in the
      9-week trastuzumab group and in 4 (1.3 %) patients in the 52-week trastuzumab
      group. CONCLUSIONS: In this study, similar outcomes were found in the 9- and 52
      week trastuzumab treatment groups.

PMID- 22878682
TI  - Challenges in creating an opt-in biobank with a registrar-based consent process
      and a commercial EHR.
AB  - Residual clinical samples represent a very appealing source of biomaterial for
      translational and clinical research. We describe the implementation of an opt-in
      biobank, with consent being obtained at the time of registration and the decision
      stored in our electronic health record, Epic. Information on that decision, along
      with laboratory data, is transferred to an application that signals to biobank
      staff whether a given sample can be kept for research. Investigators can search
      for samples using our i2b2 data warehouse. Patient participation has been
      overwhelmingly positive and much higher than anticipated. Over 86% of patients
      provided consent and almost 83% requested to be notified of any incidental
      research findings. In 6 months, we obtained decisions from over 18 000 patients
      and processed 8000 blood samples for storage in our research biobank. However,
      commercial electronic health records like Epic lack key functionality required by
      a registrar-based consent process, although workarounds exist.

PMID- 22878683
TI  - RAFTsomes containing epitope-MHC-II complexes mediated CD4+ T cell activation and
      antigen-specific immune responses.
AB  - PURPOSE: To develop a liposome formulation incorporating antigen-presenting cells
      (APCs) membrane microdomains with enriched epitope/MHC complexes to evaluate the
      activities of these liposomes (RAFTsomes) to activate T cells and prime immune
      responses. METHODS: We isolated membrane microdomain structures that contained
      the epitope/MHC complexes from ovalbumin (OVA) primed dendritic cells (DCs), and
      reconstituted them on liposomes surface by detergent dialysis. The resulted
      RAFTsomes were purified by density gradient centrifugation. Their T cell
      activation functions were evaluated by IL-2 secreting and proliferation assays in
      vitro. In vivo immune responses and the protective effect against OVA expressing
      EG.7 tumor challenge were also examined. RESULTS: Membrane microdomains
      containing enriched epitope/MHC complexes can be reconstituted into liposomes
      with defined size and composition. The integrity and activities of these
      complexes after reconstitution were confirmed by in vitro T cell assays. OVA
      epitope loaded RAFTsomes injected in vivo resulted in high anti-OVA IgG
      production (predominantly IgG1). The immunized mice were protected from EG.7
      tumor cell inoculation challenge. CONCLUSIONS: Based on these findings, we
      propose that RAFTsomes can be prepared with unique properties that may be used as
      an antigen delivery system for immunotherapeutic applications.

PMID- 22878684
TI  - Solid-solid transformation in racemic Ibuprofen.
AB  - PURPOSE: To clarify the polymorphism of racemic Ibuprofen and to determine the
      kinetic of the phase transformation that follows crystallisation of phase II.
      METHODS: Differential Scanning Calorimetry (DSC), X-ray powder diffraction and
      Hot Stage Microscopy are complementarily used to perform a kinetic investigation
      of the particular temperature range where competition between the occurrence of
      phases I and II is suspected. RESULTS: Experiments performed with the three
      techniques reveal that at 273 K the crystallisation to phase II is then followed
      by a solid-solid transition towards phase I. This transformation is exothermic
      (conversion enthalpy of 8.0 +/- 0.5 kJ/mol), which proves that the two phases
      form a monotropic set. The kinetics of conversion deduced from X-Ray experiments
      follows a Johnson-Mehl-Avrami equation and the Hot Stage Microscopy allows us to
      establish that the transformation proceeds by the growth of some nuclei of phase
      I probably formed at lower temperature. CONCLUSIONS: These results allow us to
      precise the stability pattern of racemic Ibuprofen and to establish the kinetic
      conditions of appearance and interconversion of the different phases. Therefore
      such real time resolved investigations would help if applied in the screening of
      polymorphs when competitive crystallisations occur.

PMID- 22878685
TI  - Lys05: a new lysosomal autophagy inhibitor.
AB  - Lys05 is a previously undescribed dimeric chloroquine which more potently
      accumulates in the lysosome and blocks autophagy compared with HCQ. Lys05
      produced more potent antitumor activity as a single agent both in vitro and in
      vivo in multiple human cancer cell lines and xenograft models compared with HCQ.
      Initial structure-activity relationship studies demonstrated that the increased
      activity associated with Lys05 was due to the bivalent aminoquinoline rings, C7
      Chlorine, and a short triamine linker. While lower doses of Lys05 were well
      tolerated and associated with antitumor activity, at the highest dose tested,
      Lys05 produced Paneth cell dysfunction and intestinal toxicity, similar to what
      can be observed in mice and humans with genetic defects in the autophagy gene
      ATG16L1. Lys05 is therefore a new lysosomal autophagy inhibitor that has
      potential to be developed further into a drug for cancer and other medical
      applications.

PMID- 22878686
TI  - The efficacy of intra-articular injections for pain control following the closed
      reduction and percutaneous pinning of pediatric supracondylar humeral fractures:
      a randomized controlled trial.
AB  - BACKGROUND: The purpose of this single-blinded, randomized, controlled trial was
      to compare the analgesic efficacy of intra-articular injections of bupivacaine or
      ropivacaine with that of no injection for postoperative pain control after the
      operative treatment of supracondylar humeral fractures in a pediatric population.
      METHODS: Subjects (n=124) were randomized to treatment with 0.25% bupivacaine
      (Group B) (n=42), 0.20% ropivacaine (Group R) (n=39), or no injection (Group C)
      (n=43). The opioid doses and the times of administration as well as child
      reported pain severity (Faces Pain Scale-Revised) and parent-reported pain
      severity (Total Quality Pain Management survey) were recorded. RESULTS: The
      proportion of subjects who required morphine and/or fentanyl injections was
      significantly (p=0.004) lower in Group B (10%) as compared with Group R (36%) and
      Group C (44%). On the basis of the log-rank test, the opioid-free survival rates
      were significantly greater in Group B as compared to Groups C and R. Total opioid
      consumption (morphine equivalent mg/kg) in the first seventy-two hours
      postoperatively was significantly less in Group B as compared with Group C (mean
      difference, 0.225; [95% confidence interval (CI), 0.0152 to 0.435]; p=0.036).
      Parent-reported pain scores were also significantly lower in Group B as compared
      with both Group C (mean difference, 1.81 [95% CI, 0.38 to 3.25]; p=0.014) and
      Group R (mean difference, 1.66; 95% CI, 0.20 to 3.12; p=0.027). There were no
      significant differences across the three groups in terms of self-reported pain.
      Differences between Groups R and C were not significant for any of the outcome
      variables. CONCLUSIONS: The intra-articular injection of 0.25% bupivacaine
      significantly improves postoperative pain control following the closed reduction
      and percutaneous pinning of supracondylar humeral fractures in pediatric
      patients.

PMID- 22878687
TI  - A nonlinear autoregressive Volterra model of the Hodgkin-Huxley equations.
AB  - We propose a new variant of Volterra-type model with a nonlinear auto-regressive
      (NAR) component that is a suitable framework for describing the process of AP
      generation by the neuron membrane potential, and we apply it to input-output data
      generated by the Hodgkin-Huxley (H-H) equations. Volterra models use a functional
      series expansion to describe the input-output relation for most nonlinear dynamic
      systems, and are applicable to a wide range of physiologic systems. It is
      difficult, however, to apply the Volterra methodology to the H-H model because is
      characterized by distinct subthreshold and suprathreshold dynamics. When
      threshold is crossed, an autonomous action potential (AP) is generated, the
      output becomes temporarily decoupled from the input, and the standard Volterra
      model fails. Therefore, in our framework, whenever membrane potential exceeds
      some threshold, it is taken as a second input to a dual-input Volterra model.
      This model correctly predicts membrane voltage deflection both within the
      subthreshold region and during APs. Moreover, the model naturally generates a
      post-AP afterpotential and refractory period. It is known that the H-H model
      converges to a limit cycle in response to a constant current injection. This
      behavior is correctly predicted by the proposed model, while the standard
      Volterra model is incapable of generating such limit cycle behavior. The
      inclusion of cross-kernels, which describe the nonlinear interactions between the
      exogenous and autoregressive inputs, is found to be absolutely necessary. The
      proposed model is general, non-parametric, and data-derived.

PMID- 22878688
TI  - High-capacity embedding of synfire chains in a cortical network model.
AB  - Synfire chains, sequences of pools linked by feedforward connections, support the
      propagation of precisely timed spike sequences, or synfire waves. An important
      question remains, how synfire chains can efficiently be embedded in cortical
      architecture. We present a model of synfire chain embedding in a cortical scale
      recurrent network using conductance-based synapses, balanced chains, and variable
      transmission delays. The network attains substantially higher embedding
      capacities than previous spiking neuron models and allows all its connections to
      be used for embedding. The number of waves in the model is regulated by recurrent
      background noise. We computationally explore the embedding capacity limit, and
      use a mean field analysis to describe the equilibrium state. Simulations confirm
      the mean field analysis over broad ranges of pool sizes and connectivity levels;
      the number of pools embedded in the system trades off against the firing rate and
      the number of waves. An optimal inhibition level balances the conflicting
      requirements of stable synfire propagation and limited response to background
      noise. A simplified analysis shows that the present conductance-based synapses
      achieve higher contrast between the responses to synfire input and background
      noise compared to current-based synapses, while regulation of wave numbers is
      traced to the use of variable transmission delays.

PMID- 22878689
TI  - Relating ion channel expression, bifurcation structure, and diverse firing
      patterns in a model of an identified motor neuron.
AB  - Neurons show diverse firing patterns. Even neurons belonging to a single chemical
      or morphological class, or the same identified neuron, can display different
      types of electrical activity. For example, motor neuron MN5, which innervates a
      flight muscle of adult Drosophila, can show distinct firing patterns under the
      same recording conditions. We developed a two-dimensional biophysical model and
      show that a core complement of just two voltage-gated channels is sufficient to
      generate firing pattern diversity. We propose Shab and DmNa v to be two candidate
      genes that could encode these core currents, and find that changes in Shab
      channel expression in the model can reproduce activity resembling the main firing
      patterns observed in MN5 recordings. We use bifurcation analysis to describe the
      different transitions between rest and spiking states that result from variations
      in Shab channel expression, exposing a connection between ion channel expression,
      bifurcation structure, and firing patterns in models of membrane potential
      dynamics.

PMID- 22878690
TI  - Methodology for a multinational case-population study on liver toxicity risks
      with NSAIDs: the Study of Acute Liver Transplant (SALT).
AB  - PURPOSE: The European Committee for Human Medicinal Products (CHMP) requested a
      multinational study with the aim to investigate the risk of acute liver failure
      (ALF) leading to registration for transplantation in patients exposed to non
      steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational,
      multicentre, retrospective case-population study, named SALT (Study of Acute
      Liver Transplant), is documented here. METHODS: This was a multicentre,
      multinational retrospective case-population study performed in France, Italy,
      Portugal, Greece, Ireland, the Netherlands and the UK. The study period was 3
      years (1 January 2005-31 December 2007). Cases were patients >= 18 years of age
      with ALF at the time of registration on the transplant list for liver
      transplantation who had been exposed to an NSAID within 30 days preceding the
      initial symptoms of liver disease (index date). Exposure was defined as exposure
      to any NSAID. Per country rates of NSAID-exposed transplantation-registered ALF
      were computed as the ratio of the number of cases identified in the country to
      total population exposure. Overall and per-drug sales for NSAIDs and for
      paracetamol were obtained from Intercontinental Marketing Services (IMS) Health
      for all participating countries. Population exposure was measured as the defined
      daily dose and as estimated annual number of patients exposed (primary endpoint)
      with 95 % confidence intervals. RESULTS: The study protocol was approved by the
      CHMP. Of the 57 eligible liver transplant centres, 54 agreed to participate in
      the study. All national authorizations were received with relevant administrative
      burden, mainly due to bureaucracy. CONCLUSION: The present study created a
      multinational research network to estimate population-based absolute rates of
      drug-exposed ALF leading to registration on the transplantation list. This study
      design was chosen to obtain a fast response to a public health issue, namely,
      that of an increased risk of a rare, very serious adverse reaction. This model
      could be used to study other drug-related issues in ALF.

PMID- 22878691
TI  - Switching from intravenous to oral tacrolimus and voriconazole leads to a more
      pronounced drug-drug interaction.

PMID- 22878692
TI  - A microfluidic in vitro system for the quantitative study of the stomach mucus
      barrier function.
AB  - In the stomach, a layer of gastric mucus protects the epithelial cells of the
      stomach wall against damage by the acidic digestive juices in the gastric lumen.
      Despite considerable research, the biophysical mechanisms for this acid barrier
      are not understood. We present an in vitro microfluidic tool to characterize the
      stomach acid barrier, in which purified mucin polymers are "secreted" against an
      acidic zone on chip, mimicking the in vivo secretion of gastric mucus into an
      acidic stomach lumen. This device reconstitutes both the H(+) concentration
      gradient and outward flow environment of the mucus layer in vivo. Our experiments
      demonstrate that a continuously secreted mucin layer hinders acid diffusion,
      suggesting novel insights into the barrier role of mucins. More broadly, our
      system may serve as a platform tool for studying the barrier functions provided
      by mucus layers in the body and for studying mucus drug interactions.

PMID- 22878693
TI  - Diversity and phylogenetic relationships of Wolbachia in Drosophila and other
      native Hawaiian insects.
AB  - Wolbachia is a genus of parasitic alphaproteobacteria found in arthropods and
      nematodes, and represents on of the most common, widespread endosymbionts known.
      Wolbachia affects a variety of reproductive functions in its host (e.g., male
      killing, cytoplasmic incompatibility, parthenogenesis), which have the potential
      to dramatically impact host evolution and species formation. Here, we present the
      first broad-scale study to screen natural populations of native Hawaiian insects
      for Wolbachia, focusing on the endemic Diptera. Results indicate that Wolbachia
      infects native Hawaiian taxa, with alleles spanning phylogenetic supergroups, A
      and B. The overall frequency of Wolbachia incidene in Hawaiian insects was 14%.
      The incidence of infection in native Hawaiian Diptera was 11% for individuals and
      12% for all species screened. Wolbachia was not detected in two large, widespread
      Hawaiian dipteran families-Dolichopodidae (44 spp screened) and Limoniidae (12
      spp screened). Incidence of infection within endemic Hawaiian lineages that carry
      Wolbachia was 18% in Drosophilidae species, 25% in Caliphoridae species, > 90% in
      Nesophrosyne species, 20% in Drosophila dasycnemia and 100% in Nesophrosyne
      craterigena. Twenty unique alleles were recovered in this study, of which 18 are
      newly recorded. Screening of endemic populations of D. dasycnemia across Hawaii
      Island revealed 4 unique alleles. Phylogenetic relationships and allele diversity
      provide evidence for horizontal transfer of Wolbachia among Hawaiian arthropod
      lineages.

PMID- 22878694
TI  - Update on tenofovir toxicity in the kidney.
AB  - Tenofovir (TFV) is a widely used and effective treatment for HIV infection.
      Numerous studies have shown that TFV exposure is associated with small but
      significant declines in estimated glomerular filtration rate (eGFR). However, TFV
      toxicity is targeted mainly at the proximal tubule (PT), and in severe cases can
      cause the renal Fanconi syndrome or acute kidney injury. Severe toxicity occurs
      in a minority of patients, but milder PT dysfunction is more common; the long
      term significance of this on kidney and bone health is uncertain. Recent work
      suggests that changes in eGFR on TFV therapy might be explained by inhibition of
      PT creatinine secretion rather than actual alterations in glomerular function.
      Risk factors for nephrotoxicity include pre-existing kidney disease, increased
      age, and low body mass. Mitochondria in the PT are the targets of TFV toxicity,
      but the exact mechanisms remain unclear. Substantial improvement of renal
      function occurs in many patients with TFV toxicity upon stopping therapy, but
      function does not always return to baseline. In recent years, TFV usage has been
      extended to new clinical spheres, including pediatrics, resource-poor settings
      and treatment of hepatitis B infection; theoretical reasons exist as to why some
      of these patients might be at higher or lower risk of TFV toxicity. Finally,
      strategies have been proposed to prevent TFV toxicity or enhance recovery.

PMID- 22878695
TI  - What key performance indicators can be used in occupational health?

PMID- 22878696
TI  - Child passenger safety: protecting your patients on every trip.

PMID- 22878697
TI  - Double-blind randomized clinical trial of the effects of ezetimibe on
      postprandial hyperlipidaemia and hyperglycaemia.
AB  - AIM: Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting
      Niemann-Pick C1-like 1 (NPC1L1) and reducing LDL cholesterol (LDL-C). In animals,
      ezetimibe reversed diet-induced obesity, liver steatosis, and insulin resistance.
      In humans, its potential effects on liver steatosis and insulin resistance have
      been suggested. We investigated the effects of ezetimibe on postprandial
      hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a
      double-blind randomized crossover trial. METHODS: Twenty obese men with
      hypertriglyceridaemia were assigned randomly to an ezetimibe- or a placebo
      precedence-treated group. Subjects in the ezetimibe group were treated with
      ezetimibe (10 mg/day) for the first 4 weeks, followed by a 4-week interval and
      then treated with placebo for another 4 weeks. The placebo group received these
      treatments in reverse order. Subjects were requested to fast for at least 12
      hours and then received a standard meal. Blood samples were collected at 0, 30,
      60, 120, 240, 360 and 480 minutes after the meal on Days 0, 28, 56 and 84 and
      were used to measure the lipid and glucose metabolism markers. RESULTS: Ezetimibe
      significantly decreased the postprandial serum triglyceride excursion (p=0.01)
      and fasting serum LDL-C, remnant-like particles(RLP) and ApoB48 levels (p<0.05).
      Postprandial glucose excursion, serum insulin levels, serum glucose-dependent
      insulinotropic polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) were
      not significantly affected by ezetimibe treatment. CONCLUSION: Ezetimibe restored
      the postprandial dysregulation of lipid but did not affect glucose metabolism in
      a double-blind randomized crossover trial.

PMID- 22878698
TI  - Glycated hemoglobin is associated with the complexity of coronary artery disease,
      even in non-diabetic adults.
AB  - AIM: Glycated hemoglobin (HbA1c) is associated with an increased risk of
      cardiovascular disease and death from any cause. The aim of this study was to
      examine the relationship between HbA1c value and coronary artery lesion
      complexity. METHODS: The subjects were 638 consecutive patients who underwent
      their first coronary angiography and had their HbA1c levels measured from
      December 2008 to August 2011. Sixty-one hemodialysis patients were excluded and
      577 were analyzed. The complexity of the coronary artery lesions was evaluated
      using the SYNTAX score (SXscore). The subjects were divided into quartiles
      according to either the HbA1c or the fasting plasma glucose (FPG) values.
      Logistic regression analysis (with forced entry methods) was used to predict the
      prevalence of an intermediate or high SXscore. RESULTS: Both the higher HbA1c
      quartiles (Q1 to Q4) and higher FPG quartiles were significantly associated with
      a higher SXscore (p for trend <0.0001 and 0.026, respectively). The association
      between higher HbA1c quartiles and a higher SXscore was even observed in non
      diabetic subjects (n= 433, Q1: 3.0+/-6.8, Q2: 6.9+/-15.6, Q3: 7.6+/-11.8, Q4:
      7.4+/-13.4 p for trend= 0.004). In addition, a higher HbA1c quartile
      independently predicted patients with intermediate or high SXscores (SXscore
      >=23) after adjusting for age, sex, hypertension, dyslipidemia, creatinine and
      FPG values (Odds ratio: Q1: 1.00 reference, Q2: 3.24, Q3: 3.03, Q4: 8.04).
      CONCLUSION: HbA1c is significantly associated with the complexity of coronary
      lesions. This association is even observed in non-diabetic adults. A higher HbA1c
      value is an independent predictor of the prevalence of complex coronary lesions.

PMID- 22878699
TI  - Impact of platelet reactivity on long-term clinical outcomes and bleeding events
      in Japanese patients receiving antiplatelet therapy with aspirin.
AB  - AIM: Aspirin is an antiplatelet drug widely used for the prevention of
      cardiovascular disease; however, it is known to increase bleeding events. A low
      response to aspirin was reported to correlate with poor prognosis in patients
      undergoing antiplatelet therapy with aspirin. The aim of this study was to
      evaluate the impact of the antiplatelet activity of aspirin on cardiovascular and
      bleeding events in Japanese patients. METHODS: We analyzed the clinical course of
      239 Japanese patients undergoing antiplatelet therapy with aspirin for a median
      of 64 months in this study. Their residual platelet reactivity was examined at
      enrollment and after 2 years. The co-primary endpoints were the occurrence of
      major adverse cardiac and cerebrovascular events (MACCEs) and bleeding events.
      RESULTS: The annual incidence of MACCEs and major bleeding events was 3.7% and
      0.48%, respectively. With defined criteria, 67 patients (28%) were classified as
      low responders based on the platelet aggregability measured at enrollment. Low
      response to aspirin was not associated with increased MACCEs, while it clearly
      increased MACCEs in patients less than 70 years old (low responders 36.9% vs.
      responders 14.8%, log rank p=0.008). Five major types of bleeding occurred in the
      responders, but not in low responders, although the difference was not
      statistically significant (p= 0.07). CONCLUSION: Low response to aspirin was not
      associated with the increase of long-term MACCEs, while it increased MACCEs in
      patients less than 70 years old; however, it tended to decrease major bleeding
      events in Japanese patients.

PMID- 22878700
TI  - Nicotine modulation of factor VII activating protease (FSAP) expression in human
      monocytes.
AB  - AIM: Factor VII activating protease (FSAP) is a plasma serine protease involved
      in hemostasis and remodeling processes. Increased levels of circulating FSAP
      during pregnancy and in women using oral contraceptives (OCs) indicate that the
      hormonal status critically influences FSAP expression. In this respect, the aim
      of this study was to quantify nicotine modulation of FSAP expression in human
      monocytes/macrophages isolated from healthy female smokers and non-smokers, and
      from women who use OCs and smoke. METHODS: FSAP concentration and activity were
      measured in plasma samples obtained from healthy non-pregnant, pre-menopausal,
      non-smoking women who did not use OCs (n=69), non-pregnant, pre-menopausal women
      who currently smoke and use OCs (n=43), and women who are only smokers (n=40) or
      currently use OCs (n=48). Expressions of FSAP mRNA and protein in monocytes
      isolated from healthy non-pregnant female or healthy male donors were analyzed.
      RESULTS: Strongest circulating FSAP concentration and activity occurred in women
      with combined smoking and use of OCs compared to the control group. Enhanced FSAP
      levels were also observed in smoking women when compared to non-smokers. Ex vivo
      experiments demonstrated enhanced FSAP expression in monocytes isolated from
      women using OCs and currently smoking. Nicotine enhanced FSAP mRNA and protein
      levels in monocytes. CONCLUSIONS: Monocytes from healthy female smokers show a
      constitutively enhanced FSAP expression and this effect could be replicated in
      vitro by stimulating monocytes with nicotine. The upregulation of FSAP due to
      nicotine and OC usage may be linked to a higher incidence of
      arteriothromboembolic diseases related to their usage.

PMID- 22878701
TI  - Apolipoprotein B-48 to triglyceride ratio is a novel and useful marker for
      detection of type III hyperlipidemia after antihyperlipidemic intervention.
AB  - AIM: Remnant lipoproteins are atherogenic and are accumulated in patients with
      type III hyperlipidemia (HL). Although type III HL is diagnosed by phenotyping
      apolipoprotein (apo) E, this procedure is time-consuming and inconvenient for
      routine clinical use. Clinical indices for screening type III HL in untreated HL
      patients have been proposed; however, in clinical settings, HL patients are
      promptly treated with lipid-lowering agents without diagnosing the underlying
      cause. We investigated whether existing clinical indices for screening type III
      HL as well as the apo B-48/triglyceride (TG) ratio, which was suggested to be
      related to the accumulation of small chylomicron (CM) remnants, are useful after
      the initiation of lipid-lowering therapies. METHODS: In 25 normolipidemic
      subjects and 191 treated HL patients (type I, n =6; IIa, 62; IIb, 66; III, 12;
      IV, 22; and V, 23) from Osaka University Hospital and related hospitals, fasting
      low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), TG, and apolipoproteins were measured and clinical indices were
      evaluated statistically. RESULTS: Apo B-48 levels were significantly higher in
      patients with type I, III, and V HL, and TG levels were significantly higher in
      patients with type I and V HL. The apo B-48/TG ratio was significantly higher
      only in patients with type III HL compared with other types of HL (p<0.001), and
      was statistically significant among the other clinical indices (AUC-ROC value,
      0.895; cut-off value, 0.110). CONCLUSION: The apo B-48/TG ratio is a novel and
      useful marker for detecting type III HL even after the initiation of lipid
      lowering interventions.

PMID- 22878702
TI  - Dendritic cells in atherogenesis: possible novel targets for prevention of
      atherosclerosis.
AB  - Atherosclerosis has been recognized as an inflammatory disease of the arterial
      wall, involving innate and adaptive immunity. Effector T cells are differentiated
      from naive T cells stimulated by antigen-presenting cells such as macrophages and
      dendritic cells (DCs) and play critical roles in atherogenesis. Accumulating
      evidence revealed that several subsets of regulatory T cells (Tregs) inhibit
      atherosclerotic lesion formation via inhibiting the inflammatory response of
      effector T cells. In addition, the contribution of DCs to atherogenesis has been
      demonstrated. DCs have different functions for either stimulating or inhibiting T
      cell function depending on their origin and maturation stage. In particular,
      immature DCs, which have potential for inducing Tregs and inhibiting effector T
      cells, are sometimes called 'tolerogenic DCs' and suppress immune responses.
      Epidemiological studies have highlighted the increasing prevalence of vitamin
      D(3) deficiency and its association with increased risks of cardiovascular
      diseases. Some studies have raised interest in the immunomodulatory properties of
      vitamin D(3) beyond its well-established role in bone and calcium metabolism. The
      active form of vitamin D(3) (calcitriol) induces Tregs and tolerogenic DCs, which
      are both involved in maintaining immunologic tolerance to self and harmless
      antigens. Interestingly, recent evidence suggested that DCs in the intestinal
      immune system are involved in inducing Tregs; modulating the function of DCs and
      Tregs in the intestinal immune system might have beneficial effects on
      atherosclerosis. In this review, we focus on the function of DCs in vascular
      diseases and discuss vitamin D(3) therapy for the prevention of atherosclerosis.

PMID- 22878703
TI  - Ophthalmic artery vasodilation after intranasal estradiol use in postmenopausal
      women.
AB  - AIM: The study aim was to evaluate the acute hemodynamic effects of intranasal 17
      beta-estradiol on ophthalmic arterial circulation in postmenopausal women.
      METHODS: Twenty-one healthy women in natural menopause for at least 6 months
      (mean age: 53.2+/- 2.9 years) were investigated. Each patient received 300 ug
      intranasal 17-beta-estradiol. We evaluated the heart rate, systolic and diastolic
      blood pressure, ophthalmic artery velocity at systolic and diastolic peak and its
      flow curve integral (FCI) before and 30, 60 and 180 minutes after the
      administration of the drug. RESULTS: At all time points, the ophthalmic artery
      FCI showed statistically significant variations (p<0.001) of velocity (cm/sec)
      compared to T0 (speed recorded at baseline before drug administration). Moreover,
      systolic blood pressure, diastolic blood pressure and heart rate did not
      significantly differ each other after drug administration. CONCLUSIONS:
      Administration of a single dose of intranasal 17-beta-estradiol to healthy
      postmenopausal women increases ophthalmic artery perfusion.

PMID- 22878704
TI  - High density lipoprotein cholesterol in coronary artery disease: when higher
      means later.
AB  - AIM: Although high-density lipoprotein cholesterol (HDL-C) levels are inversely
      associated with cardiovascular risk, patients with elevated HDL-C also develop
      coronary artery disease (CAD) and cardiac events. We aimed to draw the clinical
      profile of CAD patients with elevated HDL-C and to assess the prognostic impact
      of elevated HDL-C. METHODS: We prospectively examined 2322 patients (age 67+/-10
      years, 79% male) with chronic CAD, defined by >50% coronary stenosis and/or
      previous myocardial infarction. RESULTS: HDL-C levels were low (<35 mg/dL) in 736
      patients (32%), normal (35-60 mg/dL) in 1464 (63%), and high (>60 mg/dL) in 122
      (5%). Patients with elevated HDL-C were less frequently male (p<0.0001), smokers
      (p<0.0001), diabetic (p<0.0001), and obese (p<0.0015) than those with low or
      normal HDL-C, but were 3 and 5 years older, respectively (p<0.0001). During
      follow-up (median, 46 months) 143 patients died from cardiac causes and 80
      developed a non-fatal infarction. Cardiac event-free survival was lower in
      patients with low compared to normal HDL-C (p<0.0001), but was not significantly
      different from that of patients with elevated HDL-C. The prognostic impact of low
      HDL-C was independent of age, sex, diabetes, LV function, extent of coronary
      stenoses, low density lipoprotein cholesterol, triglycerides, complete blood
      count, thyroid and renal function (p<0.0001). Conversely, the prognostic impact
      of elevated HDL-C disappeared (p>0.10) after adjustment for age. CONCLUSION:
      Patients with elevated HDL-C develop CAD and cardiac events as do those with low
      or normal HDL, but at a more advanced age.

PMID- 22878705
TI  - Prenatal counseling for cloaca and cloacal exstrophy-challenges faced by
      pediatric surgeons.
AB  - INTRODUCTION: With the advance of prenatal imaging, more often pediatric surgeons
      are called for prenatal counseling in suspected cases of cloaca or cloacal
      exstrophy. This presents new challenges for pediatric surgeons since no specific
      guidelines have been established so far. The purpose of this review is to analyze
      our experience in prenatally diagnosed cloaca or cloacal exstrophy and to provide
      some guidelines for prenatal counseling of these complex congenital anomalies.
      METHODS: A retrospective review of the medical charts of patients with prenatally
      diagnosed cloaca and cloacal exstrophy who received postnatal care in our
      institution between July 2005 and March 2012 was performed. Representative images
      of prenatal studies were selected from 13 cases to illustrate different scenarios
      and the recommendations given. In addition, a review of the literature was
      performed to support our advice to parents. RESULTS: Eleven patients were female
      and two patients were male. The postnatal diagnoses were cloacal exstrophy (6),
      cloaca (5), posterior cloaca variant (1), and covered cloacal exstrophy (1). The
      selected abnormal prenatal imaging findings in these 13 patients included
      hydronephrosis (12), neural tube defect (8), omphalocele (7), lack of meconium at
      expected rectal location (7), vertebral anomaly (7), non-visualize bladder (5),
      distended bladder (5), hydrocolpos (4), dilated or echogenic bowel (3), umbilical
      cord cyst (3), separated pubic bones (2), and the "elephant trunk" sign (2). The
      prenatal diagnosis was correct in 10 cases, partially correct in two cases, and
      it was missed in one case. All parents received prenatal counseling depending on
      the specific diagnosis. CONCLUSION: The continuous technologic innovations in
      prenatal imaging make it possible to prenatally diagnose more complex anomalies
      including cloaca and cloacal exstrophy with increased levels of confidence and
      enhance the benefit of prenatal counseling. Together, these allow the parents to
      be better prepared for the condition and the care team to provide the best
      possible initial management in order to improve the outcomes of these challenging
      patients.

PMID- 22878707
TI  - Terminology.

PMID- 22878708
TI  - In search of natural quasicrystals.
AB  - The concept of quasicrystals was first introduced twenty-eight years ago and,
      since then, over a hundred types have been discovered in the laboratory under
      precisely controlled physical conditions designed to avoid crystallization. Yet
      the original theory suggested that quasicrystals can potentially be as robust and
      stable as crystals, perhaps even forming naturally. These considerations
      motivated a decade-long search for a natural quasicrystal culminating in the
      discovery of icosahedrite (Al(63)Cu(24)Fe(13)), an icosahedral quasicrystal found
      in a rock sample composed mainly of khatyrkite (crystalline (Cu,Zn)Al(2)) labeled
      as coming from the Koryak Mountains of far eastern Russia. In this paper, we
      review the search and discovery, the analysis showing the sample to be of
      extraterrestrial origin and the initial results of an extraordinary geological
      expedition to the Koryak Mountains to seek further evidence.

PMID- 22878709
TI  - [Portable sleep monitoring in patients with disorders in falling asleep or
      maintaining sleep].
AB  - BACKGROUND: The most common diagnoses in sleep medicine are insomnia, sleep
      disordered breathing (SDB) and periodic leg movements (PLM). These disorders may
      coincide. This study examined the role of portable sleep monitoring in the
      diagnostic process and which sleep medicine diagnoses are additionally found in
      patients with disorders of initiating and maintaining sleep. METHODS: A total of
      217 patients, including 103 men (47.5%) and 114 (52.5%) women aged 52.2 +/- 13.6
      years with disorders of initiating or maintaining sleep were included in the
      study. Patients with known SDB were excluded. Patients were investigated using a
      stepwise diagnostic procedure with clinical interviews, questionnaires, clinical
      examination and portable sleep recording with electromyography (EMG) of the
      tibialis anterior muscle to diagnose SDB and PLM. RESULTS: Of the patients 125
      (57.6%) were diagnosed with insomnia according to the International
      Classification of Sleep Disorders (ICSD) and 70 (56%) had no other sleep
      disorder. Out of the 217 patients SDB was found in 107 (49.3%) patients, PLM in
      90 patients (41.5%) and in 78 patients (35.9%) restless legs syndrome (RLS) was
      diagnosed. Among the 125 patients with insomnia 44 patients had RLS/PLMD and 35
      had SDB in addition whereas SDB and RLS/PLMD were found in 33 subjects. All 3
      disorders insomnia, RLS/PLMD and SDB were found in 24 subjects. CONCLUSIONS: Out
      of 217 patients with a complaint of non-restorative sleep only 125 were finally
      diagnosed with insomnia. As 25.3% of patients showed combinations of sleep
      disorders, 49.3% with SDB and 41.5% with RLS/PLMD portable monitoring with
      electromyography of the legs is recommended. The investigation with a portable
      sleep monitoring system including an EMG of the tibialis muscle is very useful in
      patients with insomnia in addition to a clinical interview and questionnaires.

PMID- 22878710
TI  - [Disorders of visual perception].
AB  - Disorders of visual perception are frequent and disabling functional consequences
      of acquired brain injury (20-40%). They also have adverse effects on the
      assessment, diagnosis and treatment of other functional disorders. Most frequent
      are visual field disorders followed by disorders of visual acuity and contrast
      sensitivity, visual adaptation, color and visual space perception as well as of
      visual recognition. Multiple visual and/or additional cognitive disorders are
      most common. The differential diagnosis of cerebral visual disorders and an
      individually tailored and specific approach in the rehabilitation are therefore
      of great importance. Compensatory treatment methods are to be preferred because
      of their efficacy, ecological validity as well as a good cost-benefit ratio.

PMID- 22878715
TI  - Oceanography: The trouble with the bubble.

PMID- 22878716
TI  - Evidence for dietary change but not landscape use in South African early
      hominins.
AB  - The dichotomy between early Homo and Paranthropus is justified partly on
      morphology. In terms of diet, it has been suggested that early Homo was a
      generalist but that Paranthropus was a specialist. However, this model is
      challenged and the issue of the resources used by Australopithecus, the presumed
      common ancestor, is still unclear. Laser ablation profiles of strontium/calcium,
      barium/calcium and strontium isotope ratios in tooth enamel are a means to
      decipher intra-individual diet and habitat changes. Here we show that the home
      range area was of similar size for species of the three hominin genera but that
      the dietary breadth was much higher in Australopithecus africanus than in
      Paranthropus robustus and early Homo. We also confirm that P. robustus relied
      more on plant-based foodstuffs than early Homo. A South African scenario is
      emerging in which the broad ecological niche of Australopithecus became split,
      and was then occupied by Paranthropus and early Homo, both consuming a lower
      diversity of foods than Australopithecus.

PMID- 22878717
TI  - Division and subtraction by distinct cortical inhibitory networks in vivo.
AB  - Brain circuits process information through specialized neuronal subclasses
      interacting within a network. Revealing their interplay requires activating
      specific cells while monitoring others in a functioning circuit. Here we use a
      new platform for two-way light-based circuit interrogation in visual cortex in
      vivo to show the computational implications of modulating different subclasses of
      inhibitory neurons during sensory processing. We find that soma-targeting,
      parvalbumin-expressing (PV) neurons principally divide responses but preserve
      stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM)
      neurons principally subtract from excitatory responses and sharpen selectivity.
      Visualized in vivo cell-attached recordings show that division by PV neurons
      alters response gain, whereas subtraction by SOM neurons shifts response levels.
      Finally, stimulating identified neurons while scanning many target cells reveals
      that single PV and SOM neurons functionally impact only specific subsets of
      neurons in their projection fields. These findings provide direct evidence that
      inhibitory neuronal subclasses have distinct and complementary roles in cortical
      computations.

PMID- 22878719
TI  - Activation of specific interneurons improves V1 feature selectivity and visual
      perception.
AB  - Inhibitory interneurons are essential components of the neural circuits
      underlying various brain functions. In the neocortex, a large diversity of GABA
      (gamma-aminobutyric acid) interneurons has been identified on the basis of their
      morphology, molecular markers, biophysical properties and innervation pattern.
      However, how the activity of each subtype of interneurons contributes to sensory
      processing remains unclear. Here we show that optogenetic activation of
      parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1)
      sharpens neuronal feature selectivity and improves perceptual discrimination.
      Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)
      mediated optical activation, we found that increased spiking of PV+ interneurons
      markedly sharpened orientation tuning and enhanced direction selectivity of
      nearby neurons. These effects were caused by the activation of inhibitory neurons
      rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3
      (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase
      IIalpha (CAMKIIalpha)-positive excitatory neurons caused no significant change in
      V1 stimulus selectivity. Moreover, the improved selectivity specifically required
      PV+ neuron activation, as activating somatostatin or vasointestinal peptide
      interneurons had no significant effect. Notably, PV+ neuron activation in awake
      mice caused a significant improvement in their orientation discrimination,
      mirroring the sharpened V1 orientation tuning. Together, these results provide
      the first demonstration that visual coding and perception can be improved by
      increased spiking of a specific subtype of cortical inhibitory interneurons.

PMID- 22878720
TI  - Doubling of marine dinitrogen-fixation rates based on direct measurements.
AB  - Biological dinitrogen fixation provides the largest input of nitrogen to the
      oceans, therefore exerting important control on the ocean's nitrogen inventory
      and primary productivity. Nitrogen-isotope data from ocean sediments suggest that
      the marine-nitrogen inventory has been balanced for the past 3,000 years (ref.
      4). Producing a balanced marine-nitrogen budget based on direct measurements has
      proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen
      fixation by approximately 200 Tg N yr-1 (refs 5, 6). Here we present data from
      the Atlantic Ocean and show that the most widely used method of measuring oceanic
      N2-fixation rates underestimates the contribution of N2-fixing microorganisms
      (diazotrophs) relative to a newly developed method. Using molecular techniques to
      quantify the abundance of specific clades of diazotrophs in parallel with rates
      of 15N2 incorporation into particulate organic matter, we suggest that the
      difference between N2-fixation rates measured with the established method and
      those measured with the new method can be related to the composition of the
      diazotrophic community. Our data show that in areas dominated by Trichodesmium,
      the established method underestimates N2-fixation rates by an average of 62%. We
      also find that the newly developed method yields N2-fixation rates more than six
      times higher than those from the established method when unicellular, symbiotic
      cyanobacteria and gamma-proteobacteria dominate the diazotrophic community. On
      the basis of average areal rates measured over the Atlantic Ocean, we calculated
      basin-wide N2-fixation rates of 14 +/- 1 Tg N yr-1 and 24 +/-1 Tg N yr-1 for the
      established and new methods, respectively. If our findings can be extrapolated to
      other ocean basins, this suggests that the global marine N2-fixation rate derived
      from direct measurements may increase from 103 +/- 8 Tg N yr-1 to 177 +/- 8 Tg N
      yr-1, and that the contribution of N2 fixers other than Trichodesmium is much
      more significant than was previously thought.

PMID- 22878721
TI  - Delayed phenology and reduced fitness associated with climate change in a wild
      hibernator.
AB  - The most commonly reported ecological effects of climate change are shifts in
      phenologies, in particular of warmer spring temperatures leading to earlier
      timing of key events. Among animals, however, these reports have been heavily
      biased towards avian phenologies, whereas we still know comparatively little
      about other seasonal adaptations, such as mammalian hibernation. Here we show a
      significant delay (0.47 days per year, over a 20-year period) in the hibernation
      emergence date of adult females in a wild population of Columbian ground
      squirrels in Alberta, Canada. This finding was related to the climatic conditions
      at our study location: owing to within-individual phenotypic plasticity, females
      emerged later during years of lower spring temperature and delayed snowmelt.
      Although there has not been a significant annual trend in spring temperature, the
      date of snowmelt has become progressively later owing to an increasing prevalence
      of late-season snowstorms. Importantly, years of later emergence were also
      associated with decreased individual fitness. There has consequently been a
      decline in mean fitness (that is, population growth rate) across the past two
      decades. Our results show that plastic responses to climate change may be driven
      by climatic trends other than increasing temperature, and may be associated with
      declines in individual fitness and, hence, population viability.

PMID- 22878725
TI  - Career paths and personality in pharmacy.
AB  - BACKGROUND: Pharmacists choose different career paths which may have different
      requirements in terms of demands and environments, irrespective of knowledge and
      intellectual capability. A contributing factor could be personality whereby
      pharmacists seek to work in an environment which is compatible with their
      personality. OBJECTIVE: To explore the relationship between personality and
      career paths taken by pharmacists. METHODS: Data regarding pharmacists'
      personality profile as determined by The Gordon Personal Profile Inventory (GPPI)
      were gathered using an anonymous survey. The inventory booklet was mailed to all
      pharmacists registered to practice in Malta who were at the time residing in the
      country. Demographic data and information regarding areas of practice was also
      gathered. Analysis was carried out using variety of statistical tests including t
      test, Manova and Multiple Correspondence Analysis. RESULTS: Most of the types of
      pharmacists considered, lie somewhat close to the average categories of the GPPI
      attributes, with those who work in importation and wholesale being the ones who
      stand out most from the rest by scoring high on self esteem, ascendency, original
      thinking, vigour, sociability. Those who work in industry and, especially, in
      hospitals are the two categories of pharmacists who seem to score low on the GPPI
      traits in general, while those who work in the Community scored high in personal
      relations and are a little more likely to score higher in cautiousness and
      responsibility. CONCLUSION: Pharmacists are not a homogeneous group of
      individuals. It is evident that their personality is a significant factor in the
      career path that they have chosen. Not all pharmacists possess personalities that
      are conducive to patient-oriented practice. Those that do not primarily possess
      the latter personality traits, appear to have chosen to practice in non
      traditional areas where, possibly, they have found a good fit with their
      personality and other factors.

PMID- 22878724
TI  - The roles of G proteins in the activation of TRPC4 and TRPC5 transient receptor
      potential channels.
AB  - TRPC4 and TRPC5 channels are important regulators of electrical excitability in
      both gastrointestinal myocytes and neurons. Much is known regarding the assembly
      and function of these channels including TRPC1 as a homotetramer or a
      heteromultimer and the roles that their interacting proteins play in controlling
      these events. Further, they are one of the best-studied targets of G protein
      coupled receptors and growth factors in general and Galphaq protein coupled
      receptor or epidermal growth factor in particular. However, our understanding of
      the roles of Galphai/o proteins on TRPC4/5 channels is still rudimentary. We
      discuss potential roles for Galphai/o proteins in channel activation in addition
      to their known role in cellular signaling.

PMID- 22878726
TI  - Peptide immobilization on polyethylene terephthalate surfaces to study specific
      endothelial cell adhesion, spreading and migration.
AB  - To control specific endothelial cell (EC) functions, cell adhesive RGDS, EC
      specific REDV and YIGSR peptides, and angiogenic SVVYGLR sequences were
      covalently immobilized onto polyethylene terephthalate (PET) surfaces for the
      purpose of cell culture. X-ray photoelectron spectroscopy, atomic force
      microscopy, fluorescence microscopy and contact angle measurement were employed
      for characterization of surface modifications. The peptide density on PET
      surfaces was evaluated by fluorescence microscopy. The surfaces immobilized with
      peptides were exposed to human umbilical vein endothelial cells to study their
      specific effects onto EC functions. The results showed that the surface
      functionalized by these peptides enhanced the EC adhesion, spreading and
      migration as compared with native PET surfaces. Specifically, the RGDS peptides
      induced more cell adhesion than other peptides. The YIGSR and SVVYGLR sequences
      induced more cell spreading and cell migration, represented by intense focal
      adhesion at the leading edges of cell spreading and migration. The bi
      functionalization of RGDS and SVVYGLR peptides (MIX) combined the advantages of
      both peptides and induced significant EC adhesion, spreading and migration. Our
      study indicates that the surface functionalization by peptides specific for ECs,
      especially the combination of RGDS with SVVYGLR or YIGSR peptides, has potential
      applications in promoting endothelialization of vascular prostheses and for
      construction of vascularized tissues in tissue engineering.

PMID- 22878727
TI  - Laser-engineered topography: correlation between structure dimensions and cell
      control.
AB  - Topographical cues have a significant impact on cell responses and by this means,
      on the fabrication of innovative implant materials. However, analysis of cell
      topography interactions in dependence of the surface feature dimensions is still
      challenging due to limitations in the fabrication technology. Here, we introduce
      surface structuring via picosecond laser systems, which enable a fast production
      of micro-sized topologies. Changes in the processing parameters further control
      the feature sizes of so-called spikes. Using surfaces with big and small spike-to
      spike-distances for comparisons, we focussed on cell adhesion via extracellular
      matrix adsorption and focal adhesion complexes, morphology, localisation and
      proliferation of fibroblasts. The observed cell control was dependent on a
      turnover point related to the structure dimensions: only big spike-to-spike
      distances reduced cell behaviour. Therefore, this technology offers a platform to
      study cell and tissue interactions with a defined microenvironment.

PMID- 22878728
TI  - Reliability and validity of diagnosing acetabular labral lesions with magnetic
      resonance arthrography.
AB  - BACKGROUND: Arthroscopic surgery of the hip is being increasingly used to
      diagnose and treat various abnormalities, including acetabular labral tears.
      Magnetic resonance arthrography has been suggested as the imaging test of choice
      for the evaluation of the acetabular labrum. There is substantial variability in
      the previously reported accuracy of magnetic resonance arthrography for
      diagnosing labral lesions. Interobserver reliability has not been established
      previously. The purpose of this study was to establish the interobserver
      reliability and the validity of magnetic resonance arthrography for detecting
      lesions of the acetabular labrum in a retrospective case series. METHODS: Two
      radiologists independently assessed the acetabular labrum on magnetic resonance
      arthrograms of ninety-five hips in ninety-three patients who underwent hip
      arthroscopy for a suspected acetabular labral lesion. Magnetic resonance
      arthrography findings were compared with the gold standard, which was defined as
      the assessment of the labrum during the hip arthroscopy. RESULTS: At arthroscopy,
      ninety-one labral lesions were identified in the ninety-five hips. The
      interobserver reliability of detecting labral lesions with magnetic resonance
      arthrography was fair (kappa=0.268). Magnetic resonance arthrography, as
      interpreted by observers A and B, showed a sensitivity of 86% and 86%,
      specificity of 75% and 50%, negative predictive value of 19% and 13%, and
      positive predictive value of 99% and 98%, respectively. CONCLUSIONS: Because of
      its limited reliability and the high prevalence of labral lesions, magnetic
      resonance arthrography provides a limited complementary benefit in the detection
      of labral lesions in patients with a high clinical suspicion of labral pathology.
      When there is a high clinical suspicion of a labral lesion, magnetic resonance
      arthrography has a poor negative predictive value and cannot be used to rule out
      a labral lesion. Physicians should critically consider whether the findings on a
      magnetic resonance arthrogram will alter the treatment strategy for an individual
      patient with a clinical suspicion of labral pathology.

PMID- 22878729
TI  - First record of picophytoplankton diversity in Central European hypersaline
      lakes.
AB  - Our survey has revealed that the phytoplankton in the anthropo-hypersaline lakes
      of the Transylvanian Basin (Romania) was often dominated by photoautotrophic
      picoplankton (PPP, cells with a diameter <2 MUm). Therefore, the aim of this
      study was to identify PPP members both in the summer and the winter communities
      using molecular biological techniques, denaturing gradient gel electrophoresis
      (DGGE) and sequence analysis. The applied PCR-DGGE methods were highly specific
      to cyanobacteria and green algae. A total of 11 different plankton taxa were
      identified that were related to several distant taxonomic groups. PPP were
      represented by a simple community and consisted of two major genotypes, one from
      the green algal species Picochlorum oklahomense and the other related to marine
      Synechococcus isolates (Cyanobacteria). These marine PPP species were recorded
      for the first time in inland saline lakes from Europe. Besides picoplankton,
      several additional marine taxa (e.g. cryptophytes and haptophytes) were detected
      among the nanoplankton species. The presence of the identified marine and
      hypersaline species could be explained by wind, precipitation or waterfowl
      transfer; however, this latter could have smaller importance.

PMID- 22878730
TI  - Atmospheric-pressure microplasma in dielectrophoresis-driven bubbles for optical
      emission spectroscopy.
AB  - The manipulation of bubbles and the ignition of microplasma within a 200 nL
      bubble at atmospheric pressure and in an inert silicone oil environment were
      achieved. Driven by dielectrophoresis (DEP), bubble generation, transportation,
      mixing, splitting, and expelling were demonstrated. This process facilitated the
      preparation of various bubbles with tuneable gas compositions. Different gas
      bubbles, including air, argon (Ar), helium (He), and Ar/He mixtures, were
      manipulated and ignited to the plasma state by dielectric barrier discharge (DBD)
      within a 50 MUm-high gap between parallel plates. Moving and splitting the
      atmospheric-pressure microplasma in different gas bubbles were achieved by DEP.
      The excited light of the microplasma was recorded by an optical spectrometer for
      the optical emission spectroscopy (OES) analyses. The characteristic peaks of
      air, Ar, and He were observed in the DEP-driven microplasma. With the capability
      to manipulate bubbles and microplasma, this platform could be used for gas
      analyses in the future.

PMID- 22878731
TI  - Evaluation of fetal skeletal malformations in deoxynivalenol-treated mice using
      microarray analysis.
AB  - Deoxynivalenol (DON [vomitoxin]), one of trichothecene mycotoxins produced by the
      fungus Fusarium, is commonly detected in cereal foods across the world. DON
      induces diverse toxic effects in humans and animals, including emesis and
      diarrhea, anorexia, and immunotoxicity, and impaired maternal reproduction and
      fetal development. Recently, the teratogenic potential of DON has been shown and
      has received much attention. DON can cause various skeletal deformities in
      fetuses, but the underlying mechanisms have not yet been fully examined. In this
      study, fetal skeletal malformations in DON-treated maternal mice were thoroughly
      investigated using microarray assay. The results showed that DON administration
      caused various skeletal defects in fetuses, including misaligned or fused
      sternebrae and vertebrae, divided or fused ribs and polydactyly, hemivertebrae,
      short toes, and tail anomalies. Microarray analysis showed that 282 genes,
      including 148 downregulated and 134 upregulated genes, were abnormally expressed
      in fetal vertebral bones after maternal DON exposure. These identified genes can
      be classified into several categories: skeletal development, carcinogenesis,
      nervous disorders, sperm development and embryogenesis, and inflammation. Of
      these, 6 genes, mostly related to bone development, were intentionally selected
      for further validation using real-time reverse transcription-Polymerase Chain
      Reaction (RT-PCR). It was confirmed that the mRNA expression of 4 genes, i.e.,
      fibrillin-1, Col9A2, 3'-phosphoadenosine 5'-phosphosulfate synthase 2, and Pax1,
      was upregulated significantly by DON administration, whereas that of 2 other
      genes, Runx2 and parathyroid hormone-like hormone, was downregulated
      significantly. Taken together, the results of our study suggest that altered
      expression of these 6 genes plays a critical role in fetal skeletal deformities
      induced by DON and thus they are worthy of further investigation.

PMID- 22878733
TI  - Kounis syndrome due to angiotensin converting enzyme inhibitor.

PMID- 22878732
TI  - Assessment of serum cotinine in patients with chronic heart failure: self
      reported versus objective smoking behaviour.
AB  - BACKGROUND: Smoking is a major risk factor in the development of coronary artery
      disease and thus chronic heart failure (HF). The value of self-reported smoking
      behaviour has not been validated in patients with HF. We sought to assess serum
      cotinine levels, a marker of recent tobacco exposure, in a cohort of clinically
      stable patients with chronic HF. METHODS AND RESULTS: We analysed serum cotinine
      values in 75 patients with chronic HF [mean age +/- SD 64 +/- 16 years, 85 %
      male, left ventricular ejection fraction 30 +/- 1 %, New York Heart Association
      class (I/II vs. III/IV) 73 %/27 %, haemoglobin (Hb) 13.4 +/- 1.5 g/dL, serum
      creatinine 1.21 +/- 0.51 mg/dL] and 30 control subjects of similar age (63 +/- 11
      years, 43 % male, Hb 14.1 +/- 1.5 g/dL, creatinine 1.12 +/- 0.92 mg/dL) using a
      chemiluminescence immunoassay. Patients were interviewed about their smoking
      habits, and routine laboratory parameters were analysed. In patients with HF,
      cotinine values ranged from undetectable to 829 MUg/L (mean 110 +/- 208 MUg/L).
      Similar findings were evident in healthy subjects with cotinine ranging from
      undetectable to 860 MUg/L (mean 105 +/- 208 MUg/L). Serum cotinine levels
      correlated with leukocyte count and haemoglobin concentration (both p < 0.05).
      Self-reported smoking behaviour did not correspond to serum cotinine level in
      serum in 16.9 % of the patients with chronic HF. No such finding was evident in
      control subjects. CONCLUSIONS: Serum cotinine measurement provides an easily
      applicable means to analyse smoking behaviour in patients with chronic HF. Its
      assessment may permit analysis of smoking deception in daily clinical routine.

PMID- 22878735
TI  - Screening and identification of polyhydroxyalkanoates producing bacteria and
      biochemical characterization of their possible application.
AB  - Polyhydroxyalkanoates (PHAs) accumulating bacteria were isolated under various
      selective conditions such as pH, salt concentrations and types of heavy metal.
      Fifty strains of bacterial isolates were found to belong to Bacillus, Proteus,
      Pseudomonas, Aeromonas, Alcaligenes and Chromobacterium, based on phenotypical
      features and genotypic investigation. Only twenty five bacterial isolates were
      selected and observed for the production of PHAs. Interestingly, bacteria
      belonging to Firmucutes Bacillus sp. produced a high amount of PHAs. The maximum
      PHAs were accumulated by B. licheniformis PHA 007 at 68.80% of dry cell weight
      (DCW). Pseudomonas sp., Aeromonas sp., Alcaligenes sp. and Chromobacterium sp.
      were recorded to produce a moderate amount of PHAs, varying from 10.00-44.32% of
      DCW. The enzymatic activity was preliminarily analyzed by the ratio of the clear
      zone diameter to colony diameter. Bacillus gave the highest ratio of hydrolysis
      zone which corresponds to the highest hydrolytic enzyme activities. Bacillus
      licheniformis PHA 007 had the highest lipase and protease activity at 2.1 and
      5.1, respectively. However, the highest amylase activity was observed in Bacillus
      sp. PHA 023 at 1.4. Determination of metabolic characteristics was also
      investigated to check for their ability to consume a wide range of substrates.
      Bacillus, Aeromonas sp. and Alcaligenes sp. had great ability to utilize a
      variety of substrates. To decrease high PHA cost, different sources of cheap
      substrates were tested for the production of PHAs. Bacillus cereus PHA 008 gave
      the maximal yield of PHA production (64.09% of DCW) when cultivated in
      anaerobically treated POME. In addition, the accumulation of PHA copolymers such
      as 3-hydroxyvalerate and 3-hydroxyhexanoate was also observed in Bacillus and
      Pseudomomas sp. strain 012 and 045, respectively. Eight of the nine isolates
      accumulated a significant amount of PHAs when inexpensive carbon sources were
      used as substrates. Here it varied from 1.69% of DCW by B. licheniformis PHA 007
      to 64.09% of DCW by B. cereus PHA 008.

PMID- 22878734
TI  - Identification and characterization of lactic acid bacteria isolated from
      traditional pickles in Sichuan, China.
AB  - The pickle, a traditional fermented vegetable product, is popular in Sichuan
      Province of China. The objective of this study was to investigate the diversity
      of dominant lactic acid bacteria (LAB) in pickles by analyzing 36 samples
      collected from 6 different regions in Sichuan Province. The LAB counts in these
      samples varied from 3.90 to 8.40 log cfu ml(-1). In total, 185 presumptive LAB
      with Gram-positive and catalase-negative properties were obtained from these
      samples using MRS agar, and those strains were identified at the species level by
      physiological tests, 16S rRNA gene sequencing and multiplex PCR assay. The
      results revealed that all isolates were accurately identified as Enterococcus
      thailandicus (2 strains), Lactobacillus alimentarius (16 strains), L. brevis (24
      strains), L. paracasei (9 strains), L. plantarum (81 strains), L. pentosus (38
      strains), L. sakei (8 strains), L. spicheri (1 strain), Leuconostoc lactis (1
      strain) and Pediococcus ethanolidurans (5 strains). The predominant LAB in
      Sichuan pickle was L. plantarum, which were isolated from most samples. The
      results also demonstrated that different regions in Sichuan Province have complex
      compositions of LAB species, and such a rich resource of LAB strains provides raw
      data for further studies involving probiotic strain selection.

PMID- 22878736
TI  - Photomanipulation of antibiotic susceptibility and biofilm formation of
      Escherichia coli heterologously expressing photoactivated adenylyl cyclase.
AB  - A cyaA-deficient Escherichia coli strain was transformed by a plasmid carrying
      the gene for BsPAC, a photoactivated adenylyl cyclase identified from a Beggiatoa
      sp., and was subjected to an antibiotic susceptibility assay and biofilm
      formation assay under a light or dark condition. Cells expressing BsPAC that were
      incubated under blue light (470 nm) were more susceptible to fosfomycin,
      nalidixic acid and streptomycin than were cells incubated in the dark. Cells
      expressing BsPAC formed more biofilms when incubated under the light than did
      cells cultured in the dark. We concluded from these observations that it is
      possible to determine the importance of cAMP in antibiotic susceptibility and
      biofilm formation of E. coli by photomanipulating the cellular cAMP level by the
      use of BsPAC. A site-directed mutant of BsPAC in which Tyr7 was replaced by Phe
      functioned even in the dark, indicating that Tyr7 plays an important role in
      photoactivation of BsPAC. Results of mutational analysis of BsPAC should
      contribute to an understanding of the molecular basis for photoactivation of the
      protein.

PMID- 22878737
TI  - Portibacter lacus gen. nov., sp.nov., a new member of the family Saprospiraceae
      isolated from a saline lake.
AB  - A strictly aerobic, Gram-negative, orange-pigmented, rod-shaped, non-motile and
      chemoheterotrophic bacteria representing a new genus and species, designated YM8
      076T, was isolated from lake water collected at a harbor on Lake Notoro,
      Hokkaido, Japan. Preliminary analysis based on the 16S rRNA gene sequence
      revealed that the novel isolate could be affiliated with the family
      Saprospiraceae of the phylum Bacteroidetes and that it showed highest sequence
      similarity (88.5%) to Haliscomenobacter hydrossis ATCC 27775T. The strain could
      be differentiated phenotypically from recognized members of the family
      Saprospiraceae. The G+C content of DNA was 53.7 mol%, MK-7 was the major
      menaquinone and iso-C15:0, iso-C15:1 and iso-C17:0 3-OH were the major cellular
      fatty acids. On the basis of polyphasic taxonomic studies, it was concluded that
      strain YM8-076T represents a new genus and species of the family Saprospiraceae.
      We propose the name Portibacter lacus gen. nov., sp. nov. for this strain; its
      type strain is YM8-076T (=KCTC 23747T=NBRC 108769T).

PMID- 22878738
TI  - Improved heterologous protein production by a tripeptidyl peptidase gene (AosedD)
      disruptant of the filamentous fungus Aspergillus oryzae.
AB  - Proteolytic degradation is one of the serious bottlenecks limiting the yields of
      heterologous protein production by Aspergillus oryzae. In this study, we selected
      a tripeptidyl peptidase gene AosedD (AO090166000084) as a candidate potentially
      degrading the heterologous protein, and performed localization analysis of the
      fusion protein AoSedD-EGFP in A. oryzae. As a result, the AoSedD-EGFP was
      observed in the septa and cell walls as well as in the culture medium, suggesting
      that AoSedD is a secretory enzyme. An AosedD disruptant was constructed to
      investigate an effect of AoSedD on the production level of heterologous proteins
      and protease activity. Both of the total protease and tripeptidyl peptidase
      activities in the culture medium of the AosedD disruptant were decreased as
      compared to those of the control strain. The maximum yields of recombinant bovine
      chymosin (CHY) and human lysozyme (HLY) produced by the AosedD disruptants showed
      approximately 2.9- and 1.7-fold increases, respectively, as compared to their
      control strains. These results suggest that AoSedD is one of the major proteases
      involved in the proteolytic degradation of recombinant proteins in A. oryzae.

PMID- 22878739
TI  - Characterization of Rhizobium naphthalenivorans sp. nov. with special emphasis on
      aromatic compound degradation and multilocus sequence analysis of housekeeping
      genes.
AB  - Three strains of aerobic chemoorganotrophic naphthalene-degrading bacteria
      (designated TSY03b(T), TSY04, and TSW01) isolated from sediment of a
      polychlorinated-dioxin-transforming microcosm were characterized. These strains
      had Gram-negative-stained, rod-shaped cells measuring 0.6-0.9 MUm in width and
      1.2-3.0 MUm in length and were motile by means of peritrichous flagella.
      Naphthalene was utilized as the sole carbon and energy source, and the
      transcription of a putative aromatic-ring hydroxylating gene was inducible by
      naphthalene. The major component of cellular fatty acids was summed feature 8
      (C18:1omega7c and/or C18:1omega6c), and significant proportions of C18:0 and
      C19:0 cyclo omega8cis were also found. The major respiratory quinone was
      ubiquinone-10. The G+C content of the DNA was 60.3-60.9 mol%. Phylogenetic
      analyses by studying sequence information on the housekeeping atpD, dnaK, glnII,
      gyrB, and recA genes as well as on 16S rRNA genes and the 16S-23S rDNA internal
      transcribed spacer region revealed that the strains grouped with members of the
      genus Rhizobium, with Rhizobium selenitireducens as their closest relative but
      formed a distinct lineage at the species level. This was confirmed by genomic DNA
      DNA hybridization studies. These phenotypic, genotypic, and phylogenetic data
      strongly suggest that our isolates should be classified under a novel species of
      the genus Rhizobium. Thus, we propose the name Rhizobium naphthalenivorans sp.
      nov. to accommodate the novel isolates. The type strain is TSY03b(T) (= NBRC
      107585T = KCTC 23252T).

PMID- 22878740
TI  - Ochratoxin A adsorption phenotype: an inheritable yeast trait.
AB  - This study aimed to evaluate the inheritance of the trait ochratoxin A adsorption
      in two wine strains of Saccharomyces cerevisiae and their 46 descendants. Each
      strain was inoculated in triplicate in test tubes containing 10 ml of must
      obtained from the Calabrian Zibibbo white grape variety, artificially
      contaminated with ochratoxin A to reach a total content of 4.10 ng/ml. The
      microvinification trials were performed at 25 degrees C. After 30 days,
      ochratoxin A values ranged from 0.74 to 3.18 ng/ml, from 0.01 to 2.69 ng/ml, and
      from 0.60 to 2.95 ng/ml respectively in wines, in lees after washing, and in the
      saline solution used to wash the lees. The analysis of OTA in wines was performed
      to find the residual toxin content after yeast activity, thus obtaining
      technological evidence of yeast influence on wine detoxification. The analysis of
      OTA in lees after washing was performed to distinguish the OTA linked to cells.
      The analysis of OTA in the saline solution used to wash the lees was performed to
      distinguish the OTA adsorbed on yeast cell walls and removed by washing, thus
      focusing on the adsorption activity of wine yeast through electrostatic and ionic
      interactions between parietal mannoproteins and OTA. Ploidy of the two parental
      strains was controlled by flow cytometry. Results demonstrated that the
      ochratoxin A adsorption is genetically controlled and is a polygenic inheritable
      trait of wine yeasts. The majority of the descendants are characterized by a
      great and significant diversity compared to their parents. Both the parental
      strains had genome sizes consistent with their being diploid, so validating the
      observed results. These findings constitute an initial step to demonstrate the
      mechanisms of inheritance and establish breeding strategies to improve the
      ochratoxin A adsorption trait in wine yeasts. This will allow a decrease in the
      ochratoxin A content of contaminated musts during winemaking, by using
      genetically improved wine yeasts.

PMID- 22878741
TI  - Acetobacter okinawensis sp. nov., Acetobacter papayae sp. nov., and Acetobacter
      persicus sp. nov.; novel acetic acid bacteria isolated from stems of sugarcane,
      fruits, and a flower in Japan.
AB  - Eleven strains of acetic acid bacteria were isolated from stems of sugarcane,
      fruits, and a flower in Japan. The isolates were separated into three groups,
      Groups I, II, and III, in the genus Acetobacter according to phylogenetic
      analysis based on 16S rRNA sequences. The isolates had sequence similarities of
      99.8-100% within the Group, 99.3-99.6% to those of the type strains of each
      related Acetobacter species, and less than 98.4% to those of the type strains of
      other Acetobacter species. Genomic DNA G+C contents of Groups I, II, and III were
      59.2-59.4, 60.5-60.7, and 58.7-58.9 mol%, respectively. The isolates in the Group
      showed high values of DNA-DNA relatedness to each other, but low values less than
      46% to the type strains of related Acetobacter species. A good correlation was
      found between the three Groups and groups based on DNA G+C contents and DNA-DNA
      relatedness. All the strains had Q-9 as the main component, and Q-8 and Q-10 as
      minor components. The isolates in the three Groups did not completely match with
      any Acetobacter species on catalase reaction, the production of ketogluconic
      acids from D-glucose, growth on ammoniac nitrogen with ethanol (Hoyer-Frateur
      medium and Frateur modified Hoyer medium), growth on 30% (w/v) D-glucose, growth
      in 10% (v/v) ethanol, or DNA G+C contents. On the basis of phylogenetic
      relationships in the genus Acetobacter and chemosystematic and phenotypic
      characteristics, the three Groups were regarded as novel species in the genus
      Acetobacter. Acetobacter okinawensis sp. nov. is proposed for Group I,
      Acetobacter papayae sp. nov. for Group II, and Acetobacter persicus sp. nov. for
      Group III.

PMID- 22878742
TI  - Comamonas terrae sp. nov., an arsenite-oxidizing bacterium isolated from
      agricultural soil in Thailand.

PMID- 22878749
TI  - A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell
      lung cancer.
AB  - INTRODUCTION: This investigator-initiated study explores the safety, maximum
      tolerated dose, clinical response, and pharmacokinetics of hydroxychloroquine
      (HCQ) with and without erlotinib in patients with advanced non-small-cell lung
      cancer. METHODS: Patients with prior clinical benefit from an epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor were randomized to HCQ or HCQ
      plus erlotinib in a 3 + 3 dose-escalation schema. RESULTS: Twenty-seven patients
      were treated, eight with HCQ (arm A) and 19 with HCQ plus erlotinib (arm B). EGFR
      mutations were detected in 74% of the patients and 85% had received two or more
      prior therapies. Arm A had no dose-limiting toxicities, but the maximum tolerated
      dose was not reached as this arm closed early to increase overall study accrual.
      In arm B, one patient each experienced grade 3 rash, nail changes, skin changes,
      nausea, dehydration, and neutropenia; one had grade 4 anemia; and one developed
      fatal pneumonitis, all considered unrelated to HCQ. There were no dose-limiting
      toxicities, therefore the highest tested dose for HCQ with erlotinib 150 mg was
      1000 mg daily. One patient had a partial response to erlotinib/HCQ, for an
      overall response rate of 5% (95% confidence interval, 1-25). This patient had an
      EGFR mutation and remained on therapy for 20 months. Administration of HCQ did
      not alter the pharmacokinetics of erlotinib. CONCLUSIONS: HCQ with or without
      erlotinib was safe and well tolerated. The recommended phase 2 dose of HCQ was
      1000 mg when given in combination with erlotinib 150 mg.

PMID- 22878751
TI  - [Radiologic and nuclear medicine diagnosis and therapy of thyroid disorders: Part
      II: Malignant thyroid diseases].
AB  - Malignant thyroid diseases have increased in recent years. The distinction
      between differentiated and non-differentiated thyroid carcinoma is essential for
      therapy and follow-up. The frequently diagnosed papillary and follicular thyroid
      carcinomas are differentiated and have a good prognosis. Clinical symptoms are
      relatively unspecific, however imaging and laboratory testing can often provide
      evidence for diagnosis of thyroid carcinoma. Therapy typically involves surgery,
      ablative radioiodine therapy and subsequent suppressive hormone substitution. The
      pillars of follow-up are diagnostic scintigraphy, sonography and laboratory
      tests. Redifferentiation or a change of the tracer can make dedifferentiated
      tumors again susceptible to nuclide therapy. New treatment options have become
      available with the introduction of tyrosine kinase inhibitors.

PMID- 22878750
TI  - Long-term outcomes of 50 cases of limited-resection trial for pulmonary ground
      glass opacity nodules.
AB  - INTRODUCTION: From 1998 to 2002, we performed a trial of prospective limited
      resection for pulmonary ground-glass opacity lesions 2 cm or smaller. This is the
      second report on the long-term outcome. METHODS: The enrollment criteria of the
      trial were as follows: pulmonary peripheral nodule less than 2 cm, diagnosis or
      suspected diagnosis of clinical T1N0M0 carcinoma with ground-glass opacity and
      lack of evident pleural indentations or vascular convergence on high-resolution
      computed tomography. Limited-resection (wedge or segment) specimens were
      intraoperatively examined by frozen section. If the nodule was confirmed as
      Noguchi type A or B with a resection margin of greater than 1 cm, the incision
      was sutured and the patient followed up. The median surveillance period was 10
      years. RESULTS: In a total of 50 enrolled participants, there were two Noguchi
      type A, 23 type B and 15 type C adenocarcinomas; five atypical adenomatous
      hyperplasias, four fibroses, and one granuloma. Although there were no patients
      with recurrence within the first 5 years, in four patients who underwent limited
      resection pulmonary adenocarcinoma developed more than 5 years after the initial
      resection, of either cut-end recurrence or metachronous primary disease.
      CONCLUSIONS: Of 26 patients who underwent limited resection, adenocarcinoma
      developed in four after more than 5 years. These were possibly cut-end
      recurrences. We concluded that 5 years is not a sufficient period for follow-up,
      and that limited resection should still be done only in a trial setting, even for
      small ground-glass opacity lesions.

PMID- 22878752
TI  - Phosphorylation of the rat Ins(1,4,5)P3 receptor at T930 within the coupling
      domain decreases its affinity to Ins(1,4,5)P3.
AB  - The Ins(1,4,5)P 3 receptor acts as a central hub for Ca ( 2+)  signaling by
      integrating multiple signaling modalities into Ca ( 2+)  release from
      intracellular stores downstream of G-protein and tyrosine kinase-coupled receptor
      stimulation. As such, the Ins(1,4,5)P 3 receptor plays fundamental roles in
      cellular physiology. The regulation of the Ins(1,4,5)P 3 receptor is complex and
      involves protein-protein interactions, post-translational modifications,
      allosteric modulation, and regulation of its sub-cellular distribution.
      Phosphorylation has been implicated in the sensitization of Ins(1,4,5)P 3
      dependent Ca ( 2+)  release observed during oocyte maturation. Here we
      investigate the role of phosphorylation at T-930, a residue phosphorylated
      specifically during meiosis. We show that a phosphomimetic mutation at T-930 of
      the rat Ins(1,4,5)P 3 receptor results in decreased Ins(1,4,5)P 3-dependent Ca (
      2+)  release and lowers the Ins(1,4,5)P 3 binding affinity of the receptor. These
      data, coupled to the sensitization of Ins(1,4,5)P 3-dependent Ca ( 2+)  release
      during meiosis, argue that phosphorylation within the coupling domain of the
      Ins(1,4,5)P 3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P 3
      receptor function.

PMID- 22878753
TI  - Is there a role for open surgery in the management of the undescended testis?

PMID- 22878754
TI  - Dismembered pyeloplasty for ureteropelvic junction syndrome treatment in
      children.
AB  - BACKGROUND: Open dismembered pyeloplasty remains the preferred surgical technique
      for ureteropelvic junction syndrome (UPJS) in most paediatric urology units. The
      authors present their experience of 230 patients and describe their form of
      presentation, treatment and early and long-term results. MATERIALS AND METHODS:
      Retrospective analysis of clinical records of 230 patients submitted to
      dismembered pyeloplasty in an 8-year period, from 1999 until 2007. Pre-operative
      data, early and long-term complications were registered. Image studies included
      renopelvic ultrasonography, mercapto-acetyl triglycine (MAG3) renal scan with
      furosemide test and, in some cases, elimination urography and retrograde
      cystography. Pre-operative and post-operative results were compared. RESULTS:
      Median age of our patients at time of surgery was 14.9 months (range: 21 days
      until 16.6 years). The majority of patients were male (72%, n = 166) and 74% (n =
      120) had pre-natal diagnosis. The majority of hydronephrosis were in the left
      side (61%, n = 141). There were only 3% of complications in early post-operative
      period: four had acute pyelonephritis, two had renocutaneous fistula and one died
      due to respiratory failure. Mean follow-up period was 5 years, ranging from 12
      months to 9.7 years. There was only one case of recurrence with the need of
      reoperation. Comparing pre-operative and post-operative imaging results, we found
      that 89% had normal renal function, 7% diminished but better than before and 2%
      equal as before surgery. CONCLUSION: Open dismembered pyeloplasty is a safe and
      effective treatment in paediatric UPJS.

PMID- 22878755
TI  - Six-year retrospective analysis of colonic perforation in neonates and infants:
      single centre experience.
AB  - BACKGROUND: Developing countries at tertiary referral centre. This study analysed
      the aetiology of colonic perforation (CP) in neonates and infants. MATERIALS AND
      METHODS: Retrospective analyses of 60 CP cases (presented from May 2005 to May
      2011) were done. RESULTS: The mean age at presentation was 8.33 +/- 0.11 days
      (range, 2-110 days). The aetiology were Hirschsprung's disease (HD), necrotising
      enterocolitis (NEC) and idiopathic perforation in 78.33% (47/60), 6.67% (4/60)
      and 15% (9/60), respectively. There were 210 patients with histopathologically
      proven HD; 22.38% (47/210) cases of HD had CP. Most common site of perforation
      was mid-transverse colon (74%, 35/47) in HD patients. All HD-associated mid
      transverse colonic, caecal, appendicular and ascending colon perforations (except
      one caecal perforation) had aganglionic recto-sigmoid region and ganglionic
      perforation site. Features of enterocolitis were not found in any HD patients.
      Two patients (3.33%) died due to sepsis. CONCLUSIONS: There was a high rate of
      primary HD-associated colonic perforation in this study. Colonic perforation may
      the initial presenting condition in HD disease. We advocate colonic biopsy to
      rule out HD in any neonate presenting with primary colonic perforation.

PMID- 22878756
TI  - Laparoscopic management of 128 undescended testes: our experience.
AB  - BACKGROUND: To describe different laparoscopic procedures in the management of
      impalpable undescended testes (UDT) and their outcome. Descriptive study.
      MATERIALS AND METHODS: The medical records of all the patients, managed
      laparoscopically for impalpable UDT between January 2008 to March 2011 at the
      department of Pediatric surgery, the Children's Hospital and The Institute of
      Child Health Lahore, Pakistan were reviewed for demography, history and clinical
      examination, investigations, operative notes, complication and outcome. RESULTS:
      There were a total of 90 patients (128 testes) with impalpable UDT managed
      laparoscopically. The mean age of presentation was 4.25 years (SD+/-3.47). In 38
      (42.2%) patients, UDT were bilateral, whereas in 33 (36.7%), these were right
      sided and in 19 (21%), these were left sided. Laparoscopic findings revealed 65
      (50.8%) testes lying higher up in the abdomen, 26 (20.3%) testes at internal
      ring, vas and vessel going into the deep ring in 22 (17%) cases and 15 (11.7%)
      atrophied/vanishing testes. Laparoscopic 2-Stage Fowler-Stephen (FS) orchidopexy
      was performed in 65 testes, laparoscopic orchidopexy was performed in 26 testes,
      laparoscopy followed by inguinal exploration and orchidopexy in 19 testes (3
      testes were atrophied) and orchidectomy was performed in 9 testes. There were
      three conversions to laparotomy, one for external iliac iatrogenic injury and two
      for adhesions of the testes with the intestine. During follow-up at 6 months, 2
      patients had testicular atrophy and the parents of 5 patients where testes could
      be brought to the scrotum neck were worried for the location. CONCLUSION:
      Laparoscopic management of impalpable UDT is an effective way of managing every
      kind of impalpable UDT. It is safe and its complications are very few.

PMID- 22878757
TI  - Does circumcision alter the periurethral uropathogenic bacterial flora.
AB  - BACKGROUND: The aim of this study was to assess the pattern of periurethral
      bacterial flora in uncircumcised boys and to evaluate the effect of circumcision
      on alteration of periurethral uropathogenic bacterial flora. MATERIALS AND
      METHODS: Pattern of periurethral bacterial flora before and after circumcision
      was studied prospectively in 124 boys. The results were analysed to compare
      change in bacterial colonisation before and after circumcision. RESULTS: The age
      range was 6 weeks to 96 months. Most (94.3%) of the boys had religious indication
      and 5.7% had medical indication for circumcision. E. coli, Proteus and Klebsiella
      were most common periurethral bacterial flora in uncircumcised subjects.
      Coagulase-negative staphylococcus and Staphylococcus aureus was most common
      periurethral bacterial flora in circumcised subjects. In 66.1% of circumcised
      subjects, no bacteria were grown from periurethral region. CONCLUSION: We
      conclude that presence of prepuce is associated with great quantity of
      periurethral bacteria, greater likelihood of the presence of high concentration
      of uropathogens and high incidence of urinary tract infection (UTI). This study
      provides circumstantial evidence supporting the idea that early circumcision may
      be beneficial for prevention of UTI.

PMID- 22878758
TI  - Early oral feeding following intestinal anastomoses in children is safe.
AB  - BACKGROUND: Oral feeding following intestinal anastomoses is frequently delayed.
      In settings with limited utilisation of parenteral nutrition, this policy is
      problematic. This report evaluates the safety of early oral feeding following
      intestinal anastomoses in children. MATERIALS AND METHODS: A prospective study
      including 64 children aged <= 12-year-old who had intestinal anastomoses for
      varying surgical indications over a 6-year period. Oral feeding was started
      within 72 hours following surgery, if there was no contraindication. RESULTS:
      There were 41 (64.1%) boys and 23 (35.9%) girls aged 6 hours to 12 years (median,
      6 years). The indication for surgery was perforated typhoid enteritis (33,
      51.6%), intestinal atresia (8, 12.5%), colostomy closure for anorectal anomaly
      (8, 12.5%), intussusception (3, 4.7%) and ileostomy closure (3, 4.7%). Type
      anastomoses were 39 (60.9%) ileoileal, 4 (6.3%) colocolic, 8 (12.5%) jejunoileal
      and 4 (6.3%) ileocolic. Oral feeding was commenced in 17 (26.6%) of the patients
      within 48 hours, 36 (56.3%) by third day and 45 (70.3%) before fifth day post
      operative. Feed-related complication occurred in 5 (7.8%) patients, 3 (8.3%) of
      which was in patients fed within 72 hours post-operative and 2 (7.1%) in those
      fed after 72 hours. Full oral feed was achieved by fifth and seventh day post
      operative in 42 (65.6%) and 61(95.3%), respectively. Two (6.1%) patients had oral
      feeding stopped and recommenced at seventh day post-operative due to feed-related
      complications. CONCLUSION: Early oral feeding following intestinal anastomoses in
      children is safe, particularly in the setting of limited availability of
      parenteral nutrition.

PMID- 22878759
TI  - Retrospective analysis of paediatric achalasia in India: single centre
      experience.
AB  - BACKGROUND: Developing countries at tertiary referral centre. The aim of this
      study was to share our experience of paediatric achalasia in Indian scenario.
      MATERIALS AND METHODS: This was a retrospective analysis of children <16 years,
      operated for achalasia at our centre, from December 1998 to December 2011.
      RESULTS: Total 40 patients (mean age 39 +/- 4.29 months), including 1 patient of
      megaesophagus were operated over 13 years of period; 17 patients (associated
      congenital H-type tracheoesophageal fistula in one patient, non- responders/ lost
      follow-up for minimum of 3 years in 16 patients) were excluded from the study.
      The response rate of parents in follow-up was 60.0%. Mean symptoms duration was
      27.88 +/- 2 months. Most common symptoms were regurgitation and failure to thrive
      (78.2%). Mean symptom scoring in follow-up after 3 year was 1 +/- 0.7 compared to
      5 +/- 0.51 at the time of admission (P < 0.012). One infant expired
      (mediastenitis), one developed adhesive intestinal obstruction and one needed
      posterior re-myotomy (for megaesophagus). There were no treatment failures in
      mean follow-up of 40.2 +/- 5.07 months. CONCLUSIONS: Cardiomyotomy with partial
      fundoplication is the best modality of treatment for paediatric achalasia cardia,
      even from parents' perspective.

PMID- 22878760
TI  - Impact of magnetic resonance urography and ultrasonography on diagnosis and
      management of hydronephrosis and megaureter in paediatric patients.
AB  - BACKGROUND: (1) To evaluate the diagnostic value of magnetic resonance urography
      (MRU) in comparison with ultrasonography (US) to determine the extent of upper
      urinary tract dilation and (2) to evaluate the impact of MRU on therapy
      management. MATERIALS AND METHODS: From January 2005 to December 2010, paediatric
      patients with hydronephrosis or megaureter who underwent MRU in addition to
      standard work-up imaging were included. Data were retrospectively collected and
      analysed in comparison with the data obtained from results by US. RESULTS: Forty
      five patients with upper urinary tract dilatation were included into the study.
      Twenty-six patients (58%) had a hydronephrosis and 19 patients (42%) presented
      with a megaureter. Diagnosis was established in all patients by multimodulary
      imaging work-up including micturating cysto-urethrography, MAG3 renography, US
      and MRU and could be confirmed in all patients who underwent surgery (n = 28).
      Hydronephrosis was detected in 26 of 26 patients by US (100% sensitivity) and in
      25 of 26 patients (96%) by MRU (Not significant (n.s.)). Megaureter was detected
      in 17 of 19 patients (sensitivity 89%) by US and in 18 of 19 patients
      (sensitivity 95%) by MRU (n.s.). In all 45 patients, MRU had no impact on
      surgical or conservative management of hydronephrosis or megaureter. CONCLUSION:
      In our experience, MRU was not superior to US in detecting hydronephrosis or
      megaureter and had no impact on the surgical or conservative management of upper
      urinary tract dilation.

PMID- 22878761
TI  - The advantages of using photographs and video images in telephone consultations
      with a specialist in paediatric surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate the advantages of a
      telephone consultation with a specialist in paediatric surgery after taking
      photographs and video images by a general practitioner for the diagnosis of some
      diseases. MATERIALS AND METHODS: This was a prospective study of the reliability
      of paediatric surgery online consultation among specialists and general
      practitioners. RESULTS: Of 26 general practitioners included in the study, 12
      were working in the city and 14 were working in districts outside the city. A
      total of 41 pictures and 3 videos of 38 patients were sent and evaluated together
      with the medical history and clinical findings. These patients were diagnosed
      with umbilical granuloma (n = 6), physiological/pathological phimosis (n = 6),
      balanitis (n = 6), hydrocele (n = 6), umbilical hernia (n = 4), smegma cyst (n =
      2), reductable inguinal hernia (n = 1), incarcerated inguinal hernia (n = 1),
      paraphimosis (n = 1), burried penis (n = 1), hypospadias (n = 1), epigastric
      hernia (n = 1), vulva synechia (n = 1), and rectal prolapse (n = 1). Twelve
      patients were asked to be referred urgently, but it was suggested that only two
      of these patients, who had paraphimosis and incarcerated inguinal hernia be
      referred in emergency conditions. It was decided that there was no need for the
      other ten patients to be referred to a specialist at night or at the weekend. All
      diagnoses were confirmed to be true, when all patients underwent examination in
      the pediatric surgery clinic in elective conditions. CONCLUSION: Evaluation of
      photographs and video images of a lesion together with medical history and
      clinical findings via a telephone consultation between a paediatric surgery
      specialist and a general practitioner provides a definitive diagnosis and
      prevents patients from being referred unnecessarily.

PMID- 22878762
TI  - Fate of abstracts presented at Association of Paediatric Surgeons of Nigeria
      annual meetings.
AB  - BACKGROUND: The purpose of this study was to examine the characteristics of
      abstracts presented at the annual scientific meetings of Association of
      Paediatric Surgeons of Nigeria and their final publication rate. MATERIALS AND
      METHODS: All abstracts accepted for presentation at the Association of Paediatric
      Surgeons of Nigeria meetings from 2004 to 2009 were identified from literature,
      search engines and other online materials. Abstracts accepted for the meetings
      but not presented during the meetings were excluded. RESULTS: A total of 153
      abstracts were examined, of which 52 (34%) resulted in publication in peer
      reviewed journals. Median time from presentation to publication was 2 years
      (range 1-5 years). The median number of abstracts presented per year was 30
      (range 25-40). About three quarters of abstracts were presented by consultants
      (114, 74.5%) and 39 (25.4%) by surgical trainees. Approximately three-quarters of
      the abstracts were case series (111, 75.8%). Case reports accounted for 22.8% of
      the abstracts. Thirty-two (39.5%) of 81 retrospective studies, 8/31 (25.8%)
      prospective studies, and 11/35 (31.4%) case reports were converted to full
      publication (P = 0.403). Abstracts on surgical infection, paediatric surgical
      oncology, and gastrointestinal tract had the highest publication rates (54.5%
      [6/11], 46.2% [6/13], and 33.3% [22/66], respectively, P = 0.237). The largest
      numbers of the reports were published in the African Journal of Paediatric
      Surgery (16 of 48; 33%), the official Journal of the Association. CONCLUSIONS:
      Only a third of presented abstracts were subsequently published in peer-reviewed
      journals. Effort to encourage the publication rates of presented abstracts by
      improving quality of research work as well as encouraging preconference
      submission of full-length articles for accepted abstracts, for publication in a
      conference supplement of the Association's journal is advised.

PMID- 22878763
TI  - Laparoscopic inguinal hernia repair in children: a single-centre experience over
      7 years.
AB  - BACKGROUND: To evaluate 209 consecutive children who underwent laparoscopic
      hernia repair over a 7-year period. Technical details and clinical results are
      reported. MATERIALS AND METHODS: A total of 284 open internal rings were closed
      laparoscopically in 209 children (142 boys and 67 girls, aged 30 days to 15
      years, mean 44 months). One 5-mm and two 3-mm instruments were used to access the
      peritoneal cavity. A 270 degrees  anterolateral peritoneal incision was made. The
      internal inguinal ring was closed with a nonabsorbable suture. RESULTS: There
      were no significant intraoperative complications. Length of procedure ranged
      between 15 and 65 minutes with a mean of 30 minutes. Postoperative hospital stay
      ranged from 1 to 9 days. Thirty children who presented with a right-sided hernia
      and 23 with a left hernia (total of 53) were found to have a patent contralateral
      internal ring on laparoscopy. Mean follow-up was 30 months. There were 2.4%
      hernia recurrences and cosmesis was excellent. CONCLUSIONS: Laparoscopic hernia
      repair in children can be a routine procedure with increasing experience and
      better learning curve of surgeons. There is clear visualization of structures and
      vas remains untouched. The recurrence rate is comparable to that of the
      traditional open approach with a superior cosmetic result.

PMID- 22878764
TI  - Laparoscopic paediatric surgery: a potential for paradigm shift in developing
      countries.
AB  - BACKGROUND: Until recently, surgical conditions in children requiring operation
      were managed by the traditional open method. The introduction of the laparoscopic
      surgical technique seems to be reversing this trend in many centres. We are
      pioneering some laparoscopic surgery procedures in our environment and the aim of
      this study was to document our experience with laparoscopic paediatric surgical
      procedures in a developing country. MATERIALS AND METHODS: This was a prospective
      analysis of all consecutive children that had laparoscopic surgery at 5 hospitals
      in Northern Nigeria from June 2008 to February 2011. RESULTS: Twenty-one patients
      had laparoscopic surgeries during the study period with a mean age of 12.5 +/-
      2.6 years and age range of 10-16 years. There were 14 females and 7 males with a
      M:F ratio of 1:2. Seven patients (33.3%) had cholecystectomies and 13 (61.9%) had
      appendicectomies and the remaining one patient (4.8%) had adhesiolysis for
      partial adhesive intestinal obstruction following previous open appendicectomy.
      The mean operating time was 89 min with a range of 45-110 min for
      appendicectomies, 55-150 min for cholecystectomies and the adhesiolysis took 50
      min. The mean hospital stay was 2 days except for the conversions that stayed up
      to 7 days. There were 2 (9.5%) conversions with no mortality. CONCLUSION: We
      solicit a paradigm shift in our approach to surgical management and implore other
      centres to embrace laparoscopic surgery in the management of surgical conditions
      in children since it confers obvious advantages over open surgery.

PMID- 22878765
TI  - Thoracoscopic sympathectomy ganglia ablation in the management of palmer
      hyperhidrosis: a decade experience in a single institution.
AB  - BACKGROUND: Hyperhidrosis can cause significant professional and social
      handicaps. Surgery is the preferred treatment modality for hyperhidrosis. There
      has been evolution in the surgical management of hyperhidrosis. This study
      evaluated the place of minimally invasive surgical approach and its long-term
      outcome in the management of hyperhidrosis. PATIENTS AND METHODS: A 10-year
      prospective study of all children and adolescents who underwent thorascopic
      sympathectomy at the Schneider Children's Hospital of Israel. Data were validated
      for the procedure and analysed for outcome of procedure. RESULTS: There were 148
      patients, 66 were males and 82 were females, with a median age of 13.8 SD +/- 4.0
      years. Two hundred and ninety-six thoracopic sympathectomies were performed with
      no conversion to open procedure. The mean operation time was 18 min. Ninety-five
      per cent of the patients were discharged the next day with a mean hospital stay
      of 1.2 days. Postoperative complications included segmental atelectasis in seven
      (4.72%) patients, pneumothorax in two (1.35%) and transient unilateral Horner's
      syndrome in one (0.67%). Seventy-one (38.8%) experienced some form of
      compensatory hyperhidrosis. Complete relief of palmer hyperdidrosis was achieved
      in all patients (mean follow-up = 5.03 +/- 1.76 years). The outcome was very
      satisfactory in 91 (61.5%) and satisfactory in 48 (32.4%). Only nine (6.1%) were
      not satisfied with the outcome. CONCLUSION: Thorascopic sympathectomy provides
      effective and satisfactory cure for palmer hyperhidrosis with acceptable
      complication rate and excellent satisfactory outcome. There is a possibility of
      compensatory sweating in some individuals.

PMID- 22878766
TI  - Appendicitis in a 14-month-old infant with respiratory symptoms.
AB  - Although appendicitis is the condition that most commonly requires emergent
      abdominal surgery in the paediatric population, less than 2% of the disease
      occurs in infants and it is even more uncommon in neonates. In this report, we
      describe a rare case of a 14-month-old child presenting with abdominal pain first
      diagnosed with upper respiratory tract infection and then admitted to our
      Paediatric Surgery Department with a final diagnosis of acute appendicitis. A
      particular attention has to be kept on children presenting with an upper
      respiratory tract infection since symptoms can mask abdominal signs. Due to high
      morbidity and mortality rate related to a delayed diagnosis, appendicitis always
      has to be considered as a possible diagnosis, in order to ensure a prompt
      treatment.

PMID- 22878767
TI  - Combined oesophageal atresia with upper pouch fistula and meconium peritonitis.
AB  - Upper pouch tracheoesophageal fistula occurs is less than 1% of all oesophageal
      atresia variants. Meconium peritonitis is a rare neonatal condition with an
      incidence of 1:30 000 live births. In this case report, we describe the
      presentation, clinical findings and management of a patient diagnosed with an
      oesophageal atresia with upper pouch fistula as well as meconium peritonitis. To
      the best of our knowledge, this is the first case such as this described in
      published literature.

PMID- 22878768
TI  - Left hepatic lobectomy in a long-term biliary atresia survivor.
AB  - Surgery was performed on day 43 for biliary atresia. Left lobectomy with
      preservation of Roux-en-y cholecystojejunostomy was performed for refractory
      cholangitis after 25 years. Our case is currently awaiting liver transplantation.
      This is the second report of liver resection in a long-term biliary atresia
      survivor in the English literature.

PMID- 22878769
TI  - A rare case of an isolated triquetrum body fracture in a 14-year-old boy.
AB  - Isolated carpal fractures are uncommon injuries usually caused by a fall on the
      outstretched hand. The patient might present with non-specific clinical signs and
      X-ray diagnosis might be difficult due to bone overlay. An isolated triquetrum
      body fracture is an absolute rarity. The treatment is easy and the outcome
      excellent but if missed, degenerative changes with chronic pain and impaired
      movement might be the consequence.

PMID- 22878770
TI  - Mucoepidermoid carcinoma of the lung in a 6-year-old boy.
AB  - Primary malignant lung tumours, especially the mucoepidermoid cancer of the
      bronchus, are very uncommon in childhood. Obtaining the diagnosis might be
      difficult due to unspecific initial symptoms but early detection and treatment is
      crucial for a good long-term survival. Bronchoscopy is considered the "gold
      standard" for making the diagnosis. The recommended therapy for a mucoepidermoid
      lung cancer is sleeve lobectomy with favourable overall survival after complete
      resection. We report the case of a 6-year-old boy with a right-upper-lobe
      bronchus tumour. The histological examination revealed a low-grade mucoepidermoid
      carcinoma.

PMID- 22878771
TI  - Splenic rupture and intracranial haemorrhage in a haemophilic neonate: case
      report and literature review.
AB  - Splenic rupture and intracranial haemorrhage are life-threatening conditions
      infrequently encountered in neonates without history of birth trauma. External
      manifestations of birth trauma; namely, capput succadeneum and cephalhematoma,
      when present raise suspicions for more serious intracranial or visceral damage.
      Rupture of normal spleen without an obvious source of trauma in haemophilic
      neonate is a rare event. The concurrence of both conditions and the unusual
      presentation make this case a rare one that is seldom encountered in the
      literature. Additionally, when splenic rupture occurs, the consensus is to employ
      all non-operative techniques aimed at salvaging the spleen, thus avoiding the
      immune-compromised state associated with splenectomy. However, in this case, we
      present a 3-day-old male with family history of haemophilia A, who was diagnosed
      with splenic rupture and bilateral subdural haematomas and underwent splenectomy,
      albeit with post-operative complications, in light of haemodynamic instability
      and high ongoing transfusion requirements.

PMID- 22878772
TI  - Anorectal malformation coexisting with Hirschsprung's disease: a report of two
      patients.
AB  - Anorectal Malformation (ARM) and Hirschsprung's Disease (HD) are common causes of
      congenital intestinal obstruction in children. Simultaneous occurrence of both
      conditions is rare. Few have been reported in Europe and Asia, but we have no
      knowledge so far of such report from Nigeria. We present two patients managed in
      our centre to highlight the challenges of management of this uncommon
      coexistence. The first patient was a 5-year-old girl who was referred to us with
      intestinal obstructive symptoms despite an apparently adequate sized ectopic
      anus. She had colostomy and rectal biopsy, which confirmed HD. She had corrective
      surgery performed through a posterior sagittal approach. She did well post
      operatively. The second patient was a 3-year-old girl who presented with features
      of intestinal obstruction, had laparatomy and was also referred to us. It was
      observed in the referral hospital during laparatomy, to have features of HD and
      rectal atresia intraoperatively. She had colostomy done and rectal biopsy
      performed at the same time, which confirmed the diagnosis of HD. She had
      simultaneous correction of both conditions through a posterior sagittal approach.
      She was in good condition at follow up. It was therefore recommended that a high
      index of suspicion of HD, should be entertained while managing patients with
      anorectal malformation.

PMID- 22878773
TI  - Colonoscopic examination of rectal bleeding in children: a report of two cases.
AB  - Rectal bleeding in children is a frightening and cause of great concern, and of
      parental anxiety. In this report, we present the value of colonoscopy to unravel
      the diagnostic conundrum often associated with rectal bleeding in children.

PMID- 22878774
TI  - Perineal hernias in children: case report and review of the literature.
AB  - Perineal hernias (pelvic floor hernias) are extremely rare occurring through
      defects in musculature of the pelvic floor. This report presents a successfully
      treated case of primary perineal hernia and takes a review of the existing
      literature. The case of a 14-month-old girl with a great perineal hernia is
      presented. Diagnosis was secured by barium enema. The pelvic defect was
      successfully treated by primary suture with prolene. The literature shows many
      different approaches for treatment of perineal hernia, such as open or
      laparoscopic mesh repair, and perineal, abdominal or combined access in the
      adult, but our case like others confirms that primary closure of the hernial
      orifice through a perineal approach is also feasible in children.

PMID- 22878775
TI  - Colostomy in neonates under local anaesthesia: indications, technique and
      outcome.
AB  - BACKGROUND: Colostomy is a resuscitative procedure in paediatric surgical
      practice. In critical patients, mortality may be high, if general anaesthesia is
      used. Local anaesthesia may be an alternative in this group of neonates. The aim
      of this article was to evaluate the indications, the technique and outcome of
      colostomy in neonates under local anaesthesia. MATERIALS AND METHODS: A
      prospective analysis of 38 neonates who had colostomy under local anaesthesia,
      from July 2008 to September 2011, in our centre. RESULTS: There were 34 boys and
      4 girls. The median age was 4 days (range 2-11 days),and all presented in a
      critical state. The indication for colostomy was anorectal malformation 37
      (97.4%) and colonic atresia 1 (2.6%). COLOSTOMY: sigmoid 7 (18.4%), descending 29
      (76.3%), transverse 2 (5.3%). The median duration of the procedure was 45 minutes
      (range 30-60 minutes). The hospital stay was 7-15 days (median 7 days) and cost
      of treatment 7000-7500 Naira (median 7500 Naira = $50). There were 5 (13.2%)
      early complications, namely, skin excoriation 2, superficial site infection 2,
      and bowel evisceration 1; mortality was 2 (5.3%). The late complications were
      stomal stenosis 1 (2.6%), colostomy diarrhoea 2 (5.3%), and parastomal hernia 2
      (5.3%). 25 (65.7%) had colostomy takedown and 13 (34%) were yet to have colostomy
      takedown. Follow-up was for 1-2 years. None of the patients had a permanent
      colostomy. CONCLUSION: Colostomy in neonates under local anaesthesia is feasible,
      safe and cost-effective. The outcome is good and may be used when neonatal
      anaesthetic expertise and intensive care facilities are lacking.

PMID- 22878776
TI  - Histopathological examination of tonsillectomy specimens: Some discussions.

PMID- 22878777
TI  - Effects of the big 2011 Thai flooding on paediatric surgeries.

PMID- 22878778
TI  - Low morbidity reported after iliac bone-graft harvesting: commentary on an
      article by Bryan J. Loeffler, MD, et al.: "Prospective observational study of
      donor-site morbidity following anterior iliac crest bone-grafting in orthopaedic
      trauma reconstruction patients".

PMID- 22878779
TI  - Examining school-based bullying interventions using multilevel discrete time
      hazard modeling.
AB  - Although schools have been trying to address bullying by utilizing different
      approaches that stop or reduce the incidence of bullying, little remains known
      about what specific intervention strategies are most successful in reducing
      bullying in the school setting. Using the social-ecological framework, this paper
      examines school-based disciplinary interventions often used to deliver
      consequences to deter the reoccurrence of bullying and aggressive behaviors among
      school-aged children. Data for this study are drawn from the School-Wide
      Information System (SWIS) with the final analytic sample consisting of 1,221
      students in grades K - 12 who received an office disciplinary referral for
      bullying during the first semester. Using Kaplan-Meier Failure Functions and
      Multi-level discrete time hazard models, determinants of the probability of a
      student receiving a second referral over time were examined. Of the seven
      interventions tested, only Parent-Teacher Conference (AOR = 0.65, p < .01) and
      Loss of Privileges (AOR = 0.71, p < .10) were significant in reducing the rate of
      the reoccurrence of bullying and aggressive behaviors. By using a social
      ecological framework, schools can develop strategies that deter the reoccurrence
      of bullying by identifying key factors that enhance a sense of connection between
      the students' mesosystems as well as utilizing disciplinary strategies that take
      into consideration student's microsystem roles.

PMID- 22878780
TI  - Genetic risk scores ascertained in early adulthood and the prediction of type 2
      diabetes later in life.
AB  - It is hoped that information garnered from studies on population genetics will
      one day be translated into a form in which it meaningfully improves the
      prediction, prevention or treatment of type 2 diabetes. Type 2 diabetes genetics
      researchers have made extraordinary progress in identifying common genetic
      variants that are associated with type 2 diabetes, which has shed light on the
      biological pathways in which molecular defects that cause the disease likely
      reside. However, the expectation that genetic discoveries will aid the prevention
      or treatment of type 2 diabetes has not, so far, been fulfilled. In a paper
      published in this edition of the journal, Vassy and colleagues (DOI:
      10.1007/s00125-012-2637-7) test the hypothesis that the predictive accuracy of
      established genetic risk markers for type 2 diabetes varies by age, with the
      predictive accuracy being greatest in younger cohorts. The authors found no
      substantive support for this hypothesis. However, a number of interesting
      questions are raised by their study concerning why risk alleles for a given
      genotype may differ in younger and older cohorts and why prospective cohort
      studies may yield results that are inconsistent with those derived from cross
      sectional studies; this commentary discusses these points.

PMID- 22878781
TI  - Vitamin D status indicators in indigenous populations in East Africa.
AB  - PURPOSE: Sufficient vitamin D status may be defined as the evolutionary
      established circulating 25-hydroxyvitamin D [25(OH)D] matching our Paleolithic
      genome. METHODS: We studied serum 25(OH)D [defined as 25(OH)D2 + 25(OH)D3] and
      its determinants in 5 East African ethnical groups across the life cycle: Maasai
      (MA) and Hadzabe (HA) with traditional life styles and low fish intakes, and
      people from Same (SA; intermediate fish), Sengerema (SE; high fish), and Ukerewe
      (UK; high fish). Samples derived from non-pregnant adults (MA, HA, SE), pregnant
      women (MA, SA, SE), mother-infant couples at delivery (UK), infants at delivery
      and their lactating mothers at 3 days (MA, SA, SE), and lactating mothers at 3
      months postpartum (SA, SE). Erythrocyte docosahexaenoic acid (RBC-DHA) was
      determined as a proxy for fish intake. RESULTS: The mean +/- SD 25(OH)D of non
      pregnant adults and cord serum were 106.8 +/- 28.4 and 79.9 +/- 26.4 nmol/L,
      respectively. Pregnancy, delivery, ethnicity (which we used as a proxy for
      sunlight exposure), RBC-DHA, and age were the determinants of 25(OH)D. 25(OH)D
      increased slightly with age. RBC-DHA was positively related to 25(OH)D, notably
      25(OH)D2. Pregnant MA (147.7 vs. 118.3) and SE (141.9 vs. 89.0) had higher
      25(OH)D than non-pregnant counterparts (MA, SE). Infant 25(OH)D at delivery in
      Ukerewe was about 65 % of maternal 25(OH)D. CONCLUSIONS: Our ancient 25(OH)D
      amounted to about 115 nmol/L and sunlight exposure, rather than fish intake, was
      the principal determinant. The fetoplacental unit was exposed to high 25(OH)D,
      possibly by maternal vitamin D mobilization from adipose tissue, reduced insulin
      sensitivity, trapping by vitamin D-binding protein, diminished deactivation, or
      some combination.

PMID- 22878782
TI  - Comparable reduction in cholesterol absorption after two different ways of
      phytosterol administration in humans.
AB  - PURPOSE: Consumption of phytosterols is a nutritional strategy to reduce
      cholesterol absorption, but the efficacy of various phytosterol intake modalities
      remains uncertain. The main objective was to investigate the effects of
      phytosterol esters (PE) provided either as a spread (dispersed in fat) during a
      mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal.
      METHODS: In a randomized, single-blinded crossover design, 12 healthy intubated
      volunteers tested three different liquid meal sequences with and without PE. The
      liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium
      enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate
      of sterols was determined in the different phases of duodenal content samples as
      function of time. A second solid fat-containing meal without sterols was consumed
      at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions
      tested were as follows: (1) no PE added (control), (2) PE in a spread added into
      a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100
      g yoghurt drink (PE-minidrink meal). RESULTS: Addition of PE decreased the
      incorporation of cholesterol into the duodenum aqueous phase including micelles.
      PE added as a spread or as a minidrink significantly and comparably lowered meal
      cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE
      minidrink, p < 0.0001) compared with the control meal. CONCLUSIONS: PE either
      dispersed in fat during a meal or micro-dispersed in a liquid form after a meal
      resulted in a markedly reduced occurrence of meal-derived cholesterol in the
      circulation at a comparable extent.

PMID- 22878783
TI  - Understanding how breast cancer patients use risk information from genomic tests.
AB  - We sought to examine how patients' treatment decisions incorporate potentially
      conflicting information from standard clinical indicators (e.g., tumor size) and
      genomic tests for breast cancer recurrence risk. Participants were 77 early stage
      breast cancer survivors who previously received genomic testing. They read six
      hypothetical vignettes that varied recurrence risk indicated by standard tests
      (low or high risk) coupled with the genomic test (low, intermediate or high
      risk). For each vignette, women reported their perceived recurrence risk and
      treatment preferences. Test results indicating high recurrence risk increased
      perception of risk and preference for chemotherapy (p < .001 for all). Perceived
      risk explained (i.e., mediated) the effect of test results on chemotherapy
      preferences. When test results conflicted, women gave more weight to genomic over
      standard test results. Hypothetical genomic test results had the intended effect
      of influencing women's perceptions of recurrence risk and interest in
      chemotherapy. 

PMID- 22878784
TI  - High occurrence of hypoxemic sleep respiratory disorders in precapillary
      pulmonary hypertension and mechanisms.
AB  - BACKGROUND: The occurrence and mechanisms of nocturnal hypoxemia in precapillary
      pulmonary hypertension (PH) are not clearly defined. METHODS: In an
      observational, prospective, and transversal design, we studied 46 clinically
      stable patients with PH and a BMI < 35 kg/m(2), an FEV(1) > 60% predicted, and
      idiopathic pulmonary arterial hypertension (n = 29) or chronic thromboembolic
      pulmonary hypertension (n = 17). They underwent nocturnal polysomnography with
      transcutaneous capnography. RESULTS: Most patients (69.6%) had New York Heart
      Association functional class II disease. Mean pulmonary artery pressure was 44 +/
      13 mm Hg, and the cardiac index was 3.2 +/- 0.6 L/min/m(2). Duration of sleep
      time spent with oxygen saturation as measured by pulse oximetry <90% was 48.9% +/
      35.9%, and 38 of 46 patients (82.6%) had nocturnal hypoxemia. Mean apnea
      hypopnea index was 24.9 +/- 22.1/h, and 41 patients (89%) had sleep apnea. The
      major mechanism of nocturnal hypoxemia was a ventilation/perfusion mismatch alone
      or associated with obstructive apneic events. Multivariate logistic regression
      identified both FEV(25%-75%) (OR, 0.9519; 95% CI, 0.9089-0.9968; P = .036) and
      mean pulmonary artery pressure (OR, 1.1068; 95% CI, 1.0062-1.2175; P = .037) as
      significant predictors of nocturnal hypoxemia. Clinical symptoms were not
      predictive of nocturnal hypoxemia. CONCLUSIONS: The occurrence of nocturnal
      hypoxemia is high in PH and should be screened for systematically. Further
      studies are needed to determine the impact of nocturnal hypoxemia on the outcome
      of patients with PH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01371669; URL:
      www.clinicaltrials.gov

PMID- 22878785
TI  - Insights into proteomic immune cell signaling and communication via data-driven
      modeling.
AB  - Over the past decade, studies applying data-driven modeling approaches have
      demonstrated significant contributions toward the integrative understanding of
      multivariate cell regulatory system operation. Here we review applications of
      several of these approaches, including principal component analysis, partial
      least squares regression, partial least squares discriminant analysis, decision
      trees, and Bayesian networks, and describe the advances they have offered in
      systems-level understanding of immune cell signaling and communication. We show
      how these approaches generate novel insights from high-throughput proteomic data,
      from classification to association to influence to mechanisms. Looking forward,
      new experimental technologies involving single-cell measurements of cytokine
      expression beckon extension of these modeling techniques to inference of immune
      cell-cell communication networks, with a goal of aiding development of improved
      vaccine therapeutics.

PMID- 22878786
TI  - Tumor infiltration in the medial resection margin predicts survival after
      pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Microscopic tumor involvement (R1) in different surgical resection
      margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma
      (PDAC) has been debated. METHODS: Clinico-pathological data for 258 patients who
      underwent PD between 2001 and 2010 were retrieved from a prospective database.
      The rates of R1 resection in the circumferential resection margin (pancreatic
      transection, medial, posterior, and anterior surfaces) and their prognostic
      influence on survival were assessed. RESULTS: For PDAC, the R1 rate was 57.1%
      (48/84) for any margin, 31.0% (26/84) for anterior surface, 42.9% (36/84) for
      posterior surface, 29.8% (25/84) for medial margin, and 7.1% (3/84) for
      pancreatic transection margin. Overall and disease-free survival for R1
      resections were significantly worse than those for R0 resection (17.2 vs. 28.7
      months, P = 0.007 and 12.3 vs. 21.0 months, P = 0.019, respectively). For
      individual margins, only medial positivity had a significant impact on survival
      (13.8 vs. 28.0 months, P < 0.001), as opposed to involvement in the anterior
      (19.7 vs. 23.3 months, P = 0.187) or posterior margin (17.5 vs. 24.2 months, P =
      0.104). Multivariate analysis demonstrated R0 medial margin was an independent
      prognostic factor (P = 0.002, HR = 0.381; 95% CI 0.207-0.701). CONCLUSION: The
      medial surgical resection margin is the most important after PD for PDAC, and an
      R1 resection here predicts poor survival.

PMID- 22878787
TI  - Artificial neural network model for predicting 5-year mortality after surgery for
      hepatocellular carcinoma: a nationwide study.
AB  - BACKGROUND: To validate the use of artificial neural network (ANN) models for
      predicting 5-year mortality in HCC and to compare their predictive capability
      with that of logistic regression (LR) models. METHODS: This study retrospectively
      compared LR and ANN models based on initial clinical data for 22,926 HCC surgery
      patients from 1998 to 2009. A global sensitivity analysis was also performed to
      assess the relative significance of input parameters in the system model and to
      rank the importance of variables. RESULTS: Compared to the LR models, the ANN
      models had a better accuracy rate in 96.57 % of cases, a better Hosmer-Lemeshow
      statistic in 0.34 of cases, and a better receiver operating characteristic curves
      in 88.51 % of cases. Surgeon volume was the most influential (sensitive)
      parameter affecting 5-year mortality followed by hospital volume and Charlson co
      morbidity index. CONCLUSIONS: In comparison with the conventional LR model, the
      ANN model in this study was more accurate in predicting 5-year mortality. Further
      studies of this model may consider the effect of a more detailed database that
      includes complications and clinical examination findings as well as more detailed
      outcome data.

PMID- 22878789
TI  - Effects and processes linking social support to caregiver health among HIV/AIDS
      affected carer-child dyads: a critical review of the empirical evidence.
AB  - There is evidence to suggest that social support may be an important resource for
      the mental and physical health of caregivers and children affected by HIV/AIDS,
      especially in HIV-endemic areas of the developing world. Drawing from theory on
      social relations and health, in this paper we argue that it is important to
      assess not only the existence and direction of associations, but also the effects
      and processes explaining these. We refer to House et al's (in Annu Rev Sociol
      14;293-318, 1988) theoretical framework on social support structures and
      processes as a guide to present and discuss findings of a systematic review of
      literature assessing the relationship between social support and health among
      caregivers living with HIV or caring for HIV/AIDS-affected children. Findings
      confirm the importance of social support for health among this population, but
      also expose the absence of empirical work deriving from the developing world, as
      well as the need for further investigation on the biopsychosocial processes
      explaining observed effects.

PMID- 22878788
TI  - Oncologically safe distal resection margins in rectal cancer patients treated
      with chemoradiotherapy.
AB  - INTRODUCTION: Although current guidelines recommend distal resection margins
      (DRM) of 2-5 cm in rectal cancer operation, smaller margins may be safe. We
      therefore assessed the impact of distal margins on outcomes in patients with
      rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) followed by
      radical resection or resection followed by adjuvant CRT. MATERIALS AND METHODS:
      This study involved 376 patients who underwent sphincter-saving resection for
      rectal adenocarcinoma and pre- or postoperative CRT between 2000 and 2006. DRMs
      were measured on pinned fixed specimens. We excluded patients who did not
      complete planned CRT and those with stage IV disease. A retrospective cross
      sectional analysis was performed. RESULTS: No significant differences in local
      recurrence (9.8 versus 7.3%; P = 0.324) and systemic recurrence (16.4 versus
      18.7%; P = 0.731) were observed in patients with DRMs of <=5 and >5 mm,
      respectively. Moreover, in each DRM category, there were no differences in local
      and systemic recurrence rates between patients who received pre- or postoperative
      CRT. DRM did not affect overall survival (P = 0.880) or 5-year survival rate
      (80.3 versus76.8%; P = 0.340). CONCLUSION: A distal margin of at least 5 mm with
      negative resection margin on frozen section does not reduce oncological safety in
      rectal cancer patients who receive pre- or postoperative CRT.

PMID- 22878790
TI  - Alcohol consumption as a barrier to prior HIV testing in a population-based study
      in rural Uganda.
AB  - Early receipt of HIV care and ART is essential for improving treatment outcomes,
      but is dependent first upon HIV testing. Heavy alcohol consumption is common in
      sub-Saharan Africa, a barrier to ART adherence, and a potential barrier to HIV
      care. We conducted a population-based study of 2,516 adults in southwestern
      Uganda from November-December 2007, and estimated the relative risk of having
      never been tested for HIV using sex-stratified Poisson models. More men (63.9 %)
      than women (56.9 %) had never been tested. In multivariable analysis, compared to
      women who had not consumed alcohol for at least 5 years, women who were current
      heavy drinkers and women who last drank alcohol 1-5 years prior, were more likely
      to have never been tested. Alcohol use was not associated with prior HIV testing
      among men. HIV testing strategies may thus need to specifically target women who
      drink alcohol.

PMID- 22878791
TI  - Ru(II) sensitized lanthanide luminescence: synthesis, photophysical properties,
      and near-infrared luminescent determination of alpha-fetal protein (AFP).
AB  - A series of dinuclear compounds of [Ru(bpy)(2)(tpphz)Ln(TTA)(3)](PF(6))(2) (tpphz
      = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:3''',4'''-j]phenazine; Ln = Er(III),
      Nd(III), Yb(III) and Gd(III); TTA = 2-thenoyltrifluoroacetone) have been prepared
      by attachment of a [Ln(TTA)(3)] fragment at the vacant diimine site of the
      luminescent mononuclear complex [Ru(bpy)(2)(tpphz)](PF(6))(2). In the solid
      state, in CH(2)Cl(2) solution and in Tris-HCl buffer solution of these dinuclear
      complexes Ru-Ln, sensitized near-infrared (NIR) luminescence is observed from Nd
      and Yb centres following excitation of the d-block unit, which results from the
      effective Ru -> Ln (Ln = Nd, Yb) energy transfer, but no Er-based NIR
      luminescence is produced. The (3)MLCT (MLCT = metal to ligand charge transfer)
      emission is partly quenched in the Ru-Nd complex, slightly increased in the Ru-Yb
      complex, and is not changed in the Ru-Ercomplex. Interestingly, alpha-fetal
      protein (AFP) tends to decrease the NIR luminescence intensity of the Ru-Nd
      complex in Tris-HCl buffer solution. A novel NIR luminescent method for the
      determination of AFP was developed with a linear range of 0.5-18 ng mL(-1), and a
      detection limit of 0.2 ng mL(-1) based on 3 times the ratio of the signal-to
      noise. Considering the attractive features, such as good selectivity, stability
      and rapidity, the proposed NIR luminescent method provides promising potential
      for AFP detection in clinical diagnosis and biomedical applications.

PMID- 22878792
TI  - Contact with horses is a risk factor for tick-borne lymphadenopathy (TIBOLA): a
      case control study.
AB  - Tick-borne lymphadenopathy (TIBOLA) is an emerging infection caused by Rickettsia
      slovaca. We describe here the seasonal, age and gender characteristics as well as
      the association with horse contact as risk factors for acquiring TIBOLA in
      comparison with another, more frequent tick-borne disease, Lyme borreliosis.We
      analysed a dataset of 855 patients diagnosed with either Lyme (n = 805) or TIBOLA
      (n = 50) disease using Fisher's exact tests and generalized linear models. Then
      we performed a matched case-control study in which all TIBOLA patients were
      paired with one Lyme patient matching in age and gender. We identified the
      species of ticks collected from the TIBOLA patients (n = 16).We found that horse
      contact was significantly more frequent among TIBOLA (34/50; 68 %) than among
      Lyme patients (110/805; 13.7 %) (OR = 13.35, p < 0.001). The younger age and
      female gender associated with higher risk of acquiring TIBOLA (OR = 3.99, p <
      0.001). Ten of the 16 ticks were D. marginatus, six were D. reticulatus
      suggesting that both species are responsible for transmitting R. slovaca. Two
      patients acquired the infection from male ticks. TIBOLA is a tick-borne zoonosis,
      which might have a specific association with horse contact.

PMID- 22878793
TI  - A preliminary study about the effects of warm priming solution on oxidative
      stress and postoperative atrial fibrillation in open heart surgery.
AB  - BACKGROUND: An important reason for production of ischemia and reperfusion injury
      and oxidative stress is the sudden and rapid changes in body temperature during
      the institution of cardiopulmonary bypass. The aim of this study was to
      investigate the effects of warm priming solution on oxidative stress and atrial
      fibrillation. METHODS: This is a preliminary prospective study on a group of 40
      patients who underwent elective coronary artery bypass grafting operation using
      cardiopulmonary bypass. Patients were randomized into two groups, each consisting
      of 20 patients; one group was primed with a solution at 20  degrees C and the
      other at 36  degrees C initially for cardiopulmonary bypass. Blood samples from
      both of the groups were drawn preoperatively and at the 15th and 60th min of
      aortic cross clamping and 24th h following the surgery. Serum malondialdehyde
      levels, protein carbonyl content and total antioxidant status were detected.
      Patients were followed for postoperative atrial fibrillation. RESULTS:
      Malondialdehyde and protein carbonyl content were found to be significantly
      higher and total antioxidant status was concordantly lower in the cold priming
      group at the 15th and 60th min, recovering to the normal range postoperatively at
      the 24th h. Patients in the cold priming group had developed a significantly
      higher rate of atrial fibrillation when compared with the patients in the warm
      priming group during the postoperative period. CONCLUSION: In conclusion,
      although this study has its limitation about the sample size it may provide an
      insight about the probable preventive effects of 36  degrees C warm priming
      solution in oxidative stress and postoperative atrial fibrillation.

PMID- 22878794
TI  - Evaluation of the implementation of a rapid streptococcal antigen test in a
      routine primary health care setting: from recommendations to practice.
AB  - BACKGROUND AND AIM: Pharyngitis is a common reason for consultation in General
      Practice. Despite the development of diagnostic criteria it remains difficult to
      clinically diagnose the bacterial type. Therefore, current guidelines recommend
      the additional use of objective tests. In Austria, the Burgenlandische
      Gebietskrankenkasse introduced a test as service for patients and regular payment
      position for GPs. It was the aim of this study to analyze this implementation
      process in General Practice and a possible change in antibiotic prescriptions.
      METHODS: The retrospective evaluation lasted from April 2006 to September 2009;
      in April 2007, rapid-streptococcal-antigen-tests (RSATs) were introduced. GPs
      were grouped into three clusters according to their use of RSATs. In addition,
      all antibiotic prescriptions within the evaluation period were analyzed and
      correlated to the three clusters before and after the implementation. RESULTS:
      The overall number of RSATs performed was 6,401. Half of the GPs utilized it
      regularly. After its introduction, the relative antibiotic prescription frequency
      was significantly reduced (17.1 vs. 16.4 %, p = 0.0001). The results for the
      subgroup analyses yielded a significant reduction for the regular user group only
      (16.0 vs. 15.0 %, p = 0.0001). CONCLUSION: GPs using the RSAT regularly seem to
      apply the test appropriately. The decrease of the relative antibiotic
      prescriptions of all GPs seems to be due to the regular user group of GPs. This
      could be interpreted as a consequence of the RSAT use. The results show a
      positive trend for an improvement in diagnostic quality and for an appropriate
      use of antibiotic prescriptions.

PMID- 22878795
TI  - Determinants of exercise capacity in dilated cardiomyopathy: a prospective,
      explorative cohort study.
AB  - BACKGROUND: Exercise capacity in patients with dilated cardiomyopathy has low
      correlation to resting left ventricular function. Dysfunctional autonomic
      activity, cardiomechanics and inflammation are associated with exercise capacity
      but were investigated under inhomogeneous situations. It remains essentially
      unclear which factor mainly determines exercise capacity in dilated
      cardiomyopathy. METHODS: In a prospective, observational study in a narrow time
      frame we assessed clinically, inflammatory, hemodynamic and, autonomic parameters
      as well as echocardiographic measures to explore independent determinants of
      exercise capacity in 28 treated patients with dilated cardiomyopathy. RESULTS:
      Right ventricular end-diastolic diameter, tricuspid regurgitation velocity, and
      sympathovagal balance were independent determinants of exercise capacity (B
      coefficient, 69; CI 95 %, 15-122; p = 0.004); (B coefficient, - 226; CI 95 %, -
      374 to - 79; p = 0.007) and (B coefficient, - 104; CI 95 %, - 172 to - 37),
      respectively. C-reactive protein, serum creatinin and body mass index were
      independently associated with right ventricular end-diastolic diameter (B
      coefficient, 0.34; CI 95 %, 0.12-0.56; p = 0.004); (B coefficient, 0.9; CI 95 %,
      0.34-1.455; p = 0.003); and (B coefficient, 0.09; CI 95 %, 0.02-0.15; p = 0.01),
      respectively. CONCLUSIONS: In stable patients with dilated cardiomyopathy,
      autonomic modulation, and right ventricular dysfunction may be the most important
      determinants of exercise capacity, whereas inflammation, kidney dysfunction, and
      body mass index are independently associated with right ventricle remodeling.

PMID- 22878796
TI  - Prediagnostic plasma antibody levels to periodontopathic bacteria and risk of
      coronary heart disease.
AB  - Many epidemiological studies have indicated that periodontitis is an important
      risk factor for coronary heart disease (CHD). We examined whether plasma antibody
      levels to 3 major periodontal pathogens, Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, and Prevotella intermedia predicted the risk of CHD
      events. A nested case-control research design (case: n = 191, control: n = 382),
      by matching gender, age, study area, date of blood collection, and time since
      last meal at blood collection, was employed in a large cohort of Japanese
      community residents.Antibody levels of periodontopathic bacteria were associated
      with risk of CHD after adjusting for BMI, smoking status, alcohol intake, history
      of hypertension, history of diabetes mellitus, exercise during leisure time, and
      perceived mental stress. The association was different by age subgroup. For
      subjects aged 40-55 years, the medium (31.7-184.9 U/mL) or high tertile plasma
      antibody level (> 184.9 U/mL) of A. actinomycetemcomitans showed higher risk of
      CHD (medium: OR = 3.72; 95% CI = 1.20-11.56, high: OR = 4.64; 95% CI = 1.52
      14.18) than the low tertile level (< 31.7 U/mL). The ORs of CHD incidence became
      higher with an increase in IgG level of A. actinomycetemcomitans (P for trend =
      0.007). For subjects aged 56-69 years, the high tertile level (> 414.1 U/mL) of
      P. intermedia was associated with higher risk of CHD (OR = 2.65; 95% CI = 1.18
      5.94) in a dose-response fashion (P for trend = 0.007). The possible role of
      periodontopathic bacteria as a risk factor for CHD incidence was suggested by the
      results of this study by the elevated antibody level to these bacteria with the
      increased risk of CHD.

PMID- 22878797
TI  - Mid-term clinical outcomes of ACS and non-ACS patients treated with everolimus
      eluting stents.
AB  - Drug-eluting stents (DES) have proven to be effective for reducing the rate of
      restenosis, whereas stent thrombosis (ST) after DES implantation has raised
      safety concerns. Everolimus-eluting stents (EES) are a new generation of DES that
      have demonstrated safety and efficacy compared with first-generation DES.
      However, the use of EES in patients presenting with acute coronary syndrome (ACS)
      has not been adequately investigated. We compared the clinical outcomes between
      the ACS and non-ACS groups treated with EES. A total of 335 consecutive patients
      who received EES implantation between January 2010 and January 2011 were
      investigated (ACS; n = 172, non-ACS; n = 163). Clinical outcome data were
      obtained for 94.3% of the patients. Follow-up angiography was performed in 58.5%
      of all patients. The median follow-up period was 8 months in both groups.
      Clinical outcomes were not statistically different between the groups. The rate
      of target lesion revascularization (TLR) was 2.5% in the ACS group and 3.8% in
      the non-ACS group (P = 0.37). MACE occurred in 8.2% of the ACS group and 10.2% of
      the non-ACS group (P = 0.54). A definite ST was identified in one patient in each
      group (P = 0.75). The unadjusted cumulative event rates estimated by the Kaplan
      Meier method and the log-rank test showed no significant difference between the
      groups for TLR, target vessel revascularization (TVR), all-cause death, or MACE.
      In conclusion, EES was safe and efficacious for patients presenting with ACS, as
      well as for those with non-ACS during a mid-term follow-up period.

PMID- 22878798
TI  - Activation of peripheral blood CD3(+) T-lymphocytes in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is a common disease with a poorly understood
      pathophysiological mechanism. Increasing evidence indicates that AF may be
      associated with immunologic inflammation responses, but it remains unclear
      whether activation of peripheral blood CD3(+) T-lymphocytes plays a role in the
      pathogenesis of AF. The aim of this study was to evaluate this phenomenon. Fifty
      paroxysmal AF patients and 56 persistent AF patients who underwent successful
      electrical cardioversion were enrolled. The percentages of CD69 and human
      leukocyte antigen DR (HLA-DR) positive peripheral blood CD3(+) T-lymphocytes,
      which indicate T-lymphocyte activation, were examined by flow cytometric analysis
      in the patients and 51 healthy controls. The patient groups had higher levels of
      CD69 and HLA-DR than the healthy controls. During the 3-month follow-up, 37
      patients had recurrence of AF (recurrence group) and 50 patients remained in
      sinus (sinus group). The CD69 and HLA-DR levels in the sinus group were all
      significantly down-regulated at follow-up compared with before cardioversion.
      However, there were no statistically significant differences between the CD69 and
      HLA-DR levels in the recurrence group at follow-up and before cardioversion. Our
      findings suggest that activation of peripheral blood CD3(+) T-lymphocytes was
      associated with AF, and might be a diagnostic or therapeutic marker.

PMID- 22878799
TI  - Comparison of the diagnostic power of transthoracic and transesophageal
      echocardiography to detect ruptured chordae tendineae.
AB  - Preoperative information concerning the severity and etiology of MR is very
      important for selecting the most appropriate surgical strategy. Ruptured chordae
      tendineae (RCT) are one of the most important preoperative findings. We compared
      the diagnostic power of transesophageal echocardiography (TEE) and transthoracic
      echocardiography (TTE) to detect RCT in patients with MR. We studied 61 patients
      with MR (30 men, 31 women; mean age, 61 +/- 12 years) who underwent mitral valve
      repair or replacement. Both TTE and TEE were performed before the operations, and
      the sensitivity and specificity of TTE and TEE to detect RCT were determined. In
      addition, other factors that influenced the detection of RCT by these two methods
      were investigated. At the time of an operation, RCT was confirmed in 39 of 61
      cases. Transesophageal echocardiography had a higher sensitivity than TTE (74%
      versus 44%; P = 0.006) to detect RCT, although the specificity was not
      significantly different. In patients with a body mass index (BMI) > 22 (P =
      0.023) or MR grade 4 (P = 0.026), TEE had a significantly higher diagnostic
      sensitivity than TTE, although there was no significant difference in patients
      with BMI < 22 or MR grade <= 3. In the lateral and medial segments of the mitral
      valve, TEE had a significantly higher diagnostic sensitivity to detect RCT than
      TTE (P = 0.0012), although there was no significant difference in the middle
      segments. There was no significant difference between TTE and TEE with respect to
      the sensitivity to detect RCT in myxomatous mitral valves. Although the
      sensitivity of TEE was higher than that of TTE to detect RCT, it was affected by
      BMI, MR grade, the RCT-presenting segments, and the etiology of MR.

PMID- 22878800
TI  - Basic echocardiographic features of patients with latent left ventricular outflow
      tract obstruction without left ventricular hypertrophy.
AB  - Left ventricular outflow tract obstruction (LVOTO) is commonly observed in
      patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy
      (LVH). While some patients develop LVOTO at rest, it can also be provoked by
      physical exertion, and hence termed latent LVOTO (L-LVOTO). Recent reports
      demonstrated that L-LVOTO develops not only in LVH patients, but also in patients
      without LVH (non-LVH). However, the prevalence and clinical prognosis of non-LVH
      patients with L-LVOTO are not yet elucidated. In this study, we retrospectively
      investigated the echocardiographic features of patients with malignancy who
      underwent dobutamine stress echocardiography (DSE) to evaluate preoperative
      cardiac risk. One hundred ninety-nine patients were found not to have LVH or
      coronary artery disease. Among them, 106 patients exhibited L-LVOTO after DSE. We
      next compared the baseline echocardiographic features of L-LVOTO (+) patients
      with those of L-LVOTO (-) patients, and identified the left ventricular outflow
      tract (LVOT) ratio (systolic LVOT diameter/diastolic LVOT diameter) as a
      significant predictor of L-LVOTO. An LVOT ratio <= 0.83 was the best cutoff value
      to detect the presence of L-LVOTO, with a sensitivity of 81.1% and specificity of
      80.6%. Overall, L-LVOTO was found to develop in almost half of non-LVH patients
      with malignancy. In addition, the baseline LVOT ratio was strongly related to the
      presence of L-LVOTO in non-LVH patients. Therefore, patients with dynamic LVOT
      narrowing may benefit from DSE to detect the presence of L-LVOTO.

PMID- 22878801
TI  - Correlation between serum concentrations of B-type natriuretic peptide and
      albumin in patients with chronic congestive heart failure.
AB  - While B-type natriuretic peptide (BNP) and hypoalbuminemia are both predictors of
      major adverse cardiac events (MACE) in patients with congestive heart failure
      (CHF), whether these markers are correlated is not known. We retrospectively
      analyzed data collected in 85 patients presenting with CHF, a left ventricular
      (LV) ejection fraction (EF) < 50%, and non-ischemic heart disease, followed for a
      mean of 38 months. Statistical analysis was performed to 1) examine the
      relationship between a) baseline BNP or albumin concentrations and b) baseline
      clinical characteristics, 2) identify the correlates of changes in (Delta) BNP
      concentrations, and Delta albumin concentrations, and 3) ascertain the prognostic
      value of each variable. Log transformed BNP was correlated with New York Heart
      Association functional class, total protein and LVEF, while albumin was
      correlated with a history of diabetes mellitus and total protein. Delta BNP and
      Delta albumin concentrations between baseline and follow-up were correlated (P <
      0.0001). The follow-up BNP and albumin concentrations were independent predictors
      of MACE.BNP and albumin were correlated with different baseline clinical
      characteristics. The long-term changes in the two markers were inversely
      correlated and both were independent predictors of CHF.

PMID- 22878802
TI  - Effects of anemia correction by erythropoiesis-stimulating agents on
      cardiovascular function in non-dialysis patients with chronic kidney disease.
AB  - Anemia is a significant risk factor for patients with chronic kidney disease
      (CKD). Here, we investigated the effects of anemia correction on cardiac
      functions in CKD patients. Pre-dialysis CKD patients (n = 171) without known risk
      factors for cardiovascular disease (CVD) other than CKD with hemoglobin (Hb)
      concentrations < 10.0 g/dL were enrolled for evaluation of cardiac functions and
      biomarkers before and after the 16-week treatment of erythropoiesis-stimulating
      agents. The treatment significantly increased Hb concentrations in all patients
      who completed the study (n = 143, 8.91 +/- 0.87 versus 11.27 +/- 1.31 g/dL; n <
      0.001) and among patients whose echocardiograms were available for evaluation (n
      = 77, 8.92 +/- 0.94 versus 11.24 +/- 1.13 g/dL; P < 0.001). The left ventricular
      mass index (LVMI) was decreased (121.3 +/- 25.8 versus 114.7 +/- 25.1 g/m(2), n =
      77, P = 0.012) and significant correlation between the change in the LVMI and Hb
      concentration was noted (P = 0.011). The levels of B-type natriuretic peptide and
      human atrial natriuretic peptide, and the cardio-thoracic ratio were
      significantly increased among subjects with Hb concentrations < 11.0 g/dL at
      completion of the study. The changes in these parameters were significantly
      correlated with the Hb concentrations (P = 0.033, P = 0.011, and P < 0.001,
      respectively). No significant differences were observed in the
      electrocardiographic parameters. Correcting Hb levels higher than those
      conventionally recommended reduced left ventricular hypertrophy and myocardial
      stress, lowering risks for CVD in pre-dialysis CKD patients.

PMID- 22878803
TI  - Combination of antihypertensive therapy in the elderly, multicenter investigation
      (CAMUI) trial.
AB  - Angiotensin receptor blockers (ARBs) with calcium channel blockers (CCBs) or
      diuretics are a widely used combination therapy for hypertensive patients. The
      present study aimed to determine which combination was better for elderly
      hypertension patients aged ? 65 years.We designed a multicentre, randomized, open
      label, parallel comparison study. Hypertensive outpatients aged ? 65 years who
      did not achieve the target blood pressure (BP < 140/90 mmHg) with usual dosages
      of ARBs were randomly assigned to switch treatment to losartan 50
      mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs. The
      primary endpoint was a change in the systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) after the 3-month treatment period, while secondary
      endpoints were changes in the BP, albuminuria, laboratory values, and cognitive
      function with the mini-mental state examination (MMSE) at baseline and after one
      year. The results from the CAMUI trial should provide new evidence for selecting
      optimal combination therapies for elderly hypertensive patients.

PMID- 22878804
TI  - Intrathoracic impedance changes reflect reverse left ventricular remodeling in
      response to cardiac resynchronization therapy in chronic heart failure patients.
AB  - Intrathoracic impedance monitoring has been reported to be useful for prediction
      of worsening chronic heart failure (CHF). However, it has not revealed the
      relation between changes in intrathoracic impedance and improvement of cardiac
      function in CHF patients with cardiac resynchronization therapy (CRT)
      implantation. Therefore, we investigated whether intrathoracic impedance change
      reflects reverse left ventricular (LV) remodeling in response to CRT in patients
      with CHF. The study subjects consisted of 29 CHF patients (23 males, mean age 64
      +/- 12 years) with CRT-defibrillator (CRT-D) implantation. The patients were
      divided into two groups based on whether the Opti-vol Fluid Index(r) reached over
      60 ohms (group A, n = 7) or not (group B, n = 22) within 6 months of observation
      after CRT-D implantation. Levels of plasma B-type natriuretic peptide (BNP) were
      measured, and LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV),
      and LV ejection fraction (LVEF) were evaluated before and 6 months after CRT-D
      implantation. In group B, BNP (556 +/- 88 pg/mL versus 330 +/- 70 pg/mL, P <
      0.05), LVEDV (177 +/- 18 mL versus 149 +/- 14 mL, P < 0.01), and LVESV (128 +/-
      14 mL versus 100 +/- 12 mL, P < 0.01) were significantly decreased 6 months after
      CRT-D implantation. LVEF (28 +/- 2% versus 35 +/- 2%, P < 0.01) was significantly
      increased after CRT-D implantation. On the other hand, no significant changes
      were detected in any parameters in group A. These data showed intrathoracic
      impedance changes reflected reverse LV remodeling in response to CRT in patients
      with CHF. Therefore, the monitoring of changes in intrathoracic impedance is
      useful for predicting CRT responders in patients with CHF.

PMID- 22878805
TI  - The periodontal pathogen Aggregatibacter actinomycetemcomitans deteriorates
      ventricular remodeling after myocardial infarction in mice.
AB  - Chronic inflammation plays a fundamental role in coronary heart disease (CHD).
      Periodontal disease is a common infectious disease and is a potential source of
      systemic inflammation. However, the effect of periodontal infection on CHD has
      not yet been proven. The purpose of this study was to determine the effect of
      periodontopathic bacteria on experimental myocardial infarction (MI). We
      implanted a chamber into the subcutaneous tissue of each male mouse.
      Aggregatibacter actinomycetemcomitans (A.a. n = 8), which is a major periodontal
      pathogen, or PBS (n = 6) was injected into the chamber. Then, MI was induced by
      permanent ligation of the left anterior descending coronary artery. To exclude
      the nonspecific effect of the pathogen, we injected A.a. into the mice without MI
      (n = 4). The plasma level of anti-A.a. antibody was statistically higher in A.a.
      infected mice than in vehicle control mice. Seven days after the myocardial
      ischemia, the A.a.-positive MI hearts showed a larger infarct size and length
      than the A.a.-negative MI mice. The A.a.-positive MI hearts showed more MOMA-2
      positive myocardial infiltrating cells compared to the A.a.-negative MI mice. The
      injection of A.a. into the mice without MI did not affect their hearts. We
      concluded that a periodontal pathogen infection might deteriorate ventricular
      remodeling after MI through inflammatory cell infiltration.

PMID- 22878806
TI  - Inducibility of atrial fibrillation caused by acute increase of atrial pressure
      in rat diseased heart with chronic atrial dilation.
AB  - Although acute atrial dilation facilitates the induction of atrial fibrillation
      (AF) in the normal heart, little is known about whether the induction of AF due
      to acute atrial dilation increases in the diseased heart. To clarify this, we
      compared the inducibility of AF by an acute increase of atrial pressure with and
      without chronic atrial dilation induced by volume- and pressure-overload in rats.
      Eight weeks after creating abdominal aortocaval shunt and aortic constriction
      rats (LVH rats, n = 8) or sham rats (n = 8), the hearts were perfused in
      Langendorff's manner. Right atrial (RA) pressure was increased from 2 cm H(2)O to
      10 cm H(2)O by the height of the reservoir. Inducibility of AF was evaluated by 5
      times burst pacing from the right atrium, and mean cycle length of AF (CL) and
      the atrial effective refractory period (AERP) were also measured. The
      inducibility of AF increased from 5 +/- 3% at 2 cm H(2)O to 50 +/- 5% at 10 cm
      H(2)O RA pressure in sham rats (P < 0.01), but not in LVH rats (20 +/- 7% to 25
      +/- 6%, NS). Mean CL and AERP in LVH rats were longer than those in sham rats. In
      addition, the AERP decreased with an increase in RA pressure from 2 cm H(2)O to
      10 cm H(2)O in sham rats, but not in LVH rats. The inducibility of AF caused by
      an acute increase of RA pressure did not increase in the diseased heart,
      suggesting that electrophysiological remodeling may play a role, at least in a
      compensated state, for the prevention of AF due to an acute increase of atrial
      pressure.

PMID- 22878807
TI  - Disruption of atherosclerotic neointima seven years after bare metal stent
      deployment.
AB  - A 58-year-old male with a history of prior myocardial infarction, hypertension,
      and dyslipidemia was admitted due to deteriorating exertional angina. A bare
      metal stent (Multilink plusTM, GUIDANT Corporation, Santa Clara, CA, USA) had
      been implanted into the proximal left anterior descending artery because of ST
      elevation myocardial infarction 7 years earlier. Optical coherence tomography
      (OCT) showed a disruption of the atherosclerotic neointima overlying the stent.
      Intravascular imaging studies and pathological studies have shown that neointima
      within a bare-metal stent often transform into atherosclerotic tissue during an
      extended period of time. In the current report, OCT demonstrated that a
      disruption of the atherosclerotic neointima has the potential to cause the
      development of unstable clinical features. OCT examinations therefore help to
      understand the pathogenesis of acute coronary syndrome after stent implantation.

PMID- 22878808
TI  - Clinically significant thrombosis in pediatric heart transplant recipients during
      their waiting period.
AB  - Thrombosis is a serious complication of heart failure for which available data on
      pediatric patients are scarce. This report describes the frequency and risk
      factors of clinically significant thrombosis (CST) for children awaiting
      transplantation. A retrospective study analyzed a cohort of heart recipients with
      CST, defined by the presence of intracardiac thrombus by imaging, explant
      pathology, or symptomatic clinical event. Among the 123 patients in the study, 56
      % were male and 44 % had congenital heart disease. The median age at
      transplantation was 6.6 years (range 0-30 years). The prevalence of CST was 12.2
      % (15/123), and its incidence was 32.7 events per 100 patient-years. The
      thromboembolic event frequencies were 2.4 % and 6.5 events per 100 patient-years.
      The median interval from listing to CST was eight days (range 0-113 days). The
      median wait-list duration was 31 days (range 8-169 days) in the CST group versus
      51 days (range 0-1,743 days) in the non-CST group. Inpatient status was
      statistically associated with CST (14 of 15 subjects were inpatients, p = 0.03).
      Inotropic support (p = 0.068) and United Network for Organ Sharing (UNOS) status
      1 (p = 0.061) approached significance. Clinically significant thrombosis was
      common in this end-stage heart failure population. Until randomized clinical
      trial data are available, it may be reasonable to consider anticoagulation for
      children admitted with decompensated heart failure and listed as UNOS status 1.

PMID- 22878809
TI  - Anomalous left pulmonary artery without sling formation.
AB  - A case of aberrant left pulmonary artery originating from the right pulmonary
      artery resembling pulmonary artery sling malformation, but without true sling
      formation, is presented. Anomalous left pulmonary artery was accompanied with
      long-segment proximal tracheal stenosis and other congenital malformations
      typically associated with PAS complex. The anomalous pulmonary artery passed
      anterior to the trachea; therefore, no true sling was formed. Because no airway
      compression by the aberrant left pulmonary artery was detected, the proximal
      tracheal stenosis was thought to be primary. 

PMID- 22878810
TI  - Research in congenital heart disease: a comparative bibliometric analysis between
      developing and developed countries.
AB  - Congenital heart disease (CHD) is the most common congenital anomaly, affecting 1
      % of live births. The field of pediatric cardiology has witnessed major advances
      over the past 25 years triggered by research initiatives focusing on CHD.
      However, large disparities exist in research capabilities between Arab developing
      nations and the developed nations. This study used bibliometric analysis to
      assess the contribution of the Arab countries to CHD research. To identify
      articles on CHD published in the Arab countries, the United States, and Europe, a
      systematic search was run on MEDLINE, PubMed, and Scopus. The Arab countries,
      with an estimated population of 362 million, published 530 research articles
      addressing CHD in the last 25 years (average, 1.5 articles/10(6) population).
      This compares with 12,936 research articles published in the United States
      (average, 41 articles/10(6) population) and 12,260 published in Europe (average,
      24.3 articles/10(6) population). Basic research relating to genetics and animal
      models of CHD is emerging sparsely in the Arab world, with few articles published
      in high-impact-factor journals. The Arab world research output in the field of
      CHD per capita is substantially low, estimated to be 29 times less than in
      developed countries. Despite the minimal increase in published research articles
      in global periodicals, most of the research relating to CHD continues to be far
      from innovative. Regional collaborations with international linkage are starting
      to evolve. The research facilities in the Arab countries need to increase
      substantially in research and infrastructure funding to keep up with the pace of
      research in developing countries.

PMID- 22878811
TI  - Optical imaging techniques in microfluidics and their applications.
AB  - Microfluidic devices have undergone rapid development in recent years and provide
      a lab-on-a-chip solution for many biomedical and chemical applications. Optical
      imaging techniques are essential in microfluidics for observing and extracting
      information from biological or chemical samples. Traditionally, imaging in
      microfluidics is achieved by bench-top conventional microscopes or other bulky
      imaging systems. More recently, many novel compact microscopic techniques have
      been developed to provide a low-cost and portable solution. In this review, we
      provide an overview of optical imaging techniques used in microfluidics followed
      with their applications. We first discuss bulky imaging systems including
      microscopes and interferometer-based techniques, then we focus on compact imaging
      systems that can be better integrated with microfluidic devices, including
      digital in-line holography and scanning-based imaging techniques. The
      applications in biomedicine or chemistry are also discussed along with the
      specific imaging techniques.

PMID- 22878812
TI  - Innate immunity: TLR13, unlucky, but just for some.

PMID- 22878813
TI  - Vaccination: Oral vaccine induces genitorectal immunity.

PMID- 22878814
TI  - Latent structure analysis of the process variables and pharmaceutical responses
      of an orally disintegrating tablet.
AB  - A multivariate statistical technique was applied to the design of an orally
      disintegrating tablet and to clarify the causal correlation among variables of
      the manufacturing process and pharmaceutical responses. Orally disintegrating
      tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation
      method using crystal transition from the delta to the beta form of mannitol.
      Process parameters (water amounts (X(1)), kneading time (X(2)), compression force
      (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a
      nonlinear response surface method (RSM) incorporating a thin plate spline
      interpolation (RSM-S). The results of a verification study revealed that the
      experimental responses, such as tensile strength and disintegration time,
      coincided well with the predictions. A latent structure analysis of the
      pharmaceutical formulations of the tablet performed using a Bayesian network led
      to the clear visualization of a causal connection among variables of the
      manufacturing process and tablet characteristics. The quantity of beta-mannitol
      in the granules (Q(beta)) was affected by X(2) and influenced all granule
      properties. The specific surface area of the granules was affected by X(1) and
      Q(beta) and had an effect on all tablet characteristics. Moreover, the causal
      relationships among the variables were clarified by inferring conditional
      probability distributions. These techniques provide a better understanding of the
      complicated latent structure among variables of the manufacturing process and
      tablet characteristics.

PMID- 22878815
TI  - A partnership between the academic and the community.

PMID- 22878816
TI  - Randomized controlled trials and 21st century epistemology.

PMID- 22878817
TI  - Ten years of progress in melanoma.

PMID- 22878818
TI  - Chest wall leiomyosarcoma after breast-conservative therapy for early-stage
      breast cancer in a young woman with Li-Fraumeni syndrome.
AB  - Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer
      susceptibility syndromes, characterized by early age at tumor onset and a wide
      spectrum of malignant tumors. Identifying LFS in patients with cancer is
      clinically imperative because they have an increased sensitivity to ionizing
      radiation and are more likely to develop radiation-induced secondary
      malignancies. This case report describes a young woman whose initial presentation
      of LFS was early-onset breast cancer and whose treatment of this primary
      malignancy with breast conservation likely resulted in a secondary malignancy
      arising in her radiation field. As seen in this case, most breast cancers in
      patients with LFS exhibit a triple-positive phenotype (estrogen receptor
      positive/progesterone receptor-positive/HER2-positive). Although this patient met
      classic LFS criteria based on age and personal and family history of cancer, the
      NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk
      Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53
      mutations in a subset of patients with early-onset breast cancer, even in the
      absence of a suggestive family history, because of the potential for de novo TP53
      mutations.

PMID- 22878819
TI  - The first documented case of high-grade synovial cell sarcoma of the rectum.
AB  - A patient presented with signs and symptoms of tenesmus, urgency, and rectal
      bleeding that she had been experiencing over the course of several months. Full
      endoscopic evaluation showed a 6-cm submucosal mass approximately 10 cm from the
      dente line projecting as an endoluminal mass with a large broad base. An initial
      endoscopic resection was attempted but aborted because of significant hemorrhage,
      and surgical oncology was consulted. After stabilization, the patient underwent a
      transanal resection of the mass the following day. An endoscopic gastrointestinal
      anastomosis stapler resulted in a margin-negative complete resection of what was
      later determined to be a high-grade synovial cell sarcoma. This case report
      presents the first known documented case of synovial cell sarcoma of the rectum.

PMID- 22878820
TI  - Soft tissue sarcoma, version 2.2012: featured updates to the NCCN guidelines.
AB  - The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma
      pertain to the management of patients with gastrointestinal stromal tumors
      (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib
      following complete resection for primary GIST with no preoperative imatinib is
      now included as a category 1 recommendation for patients with intermediate or
      high risk of recurrence. The panel also reaffirmed the recommendation for
      preoperative use of imatinib in patients with GISTs that are resectable with
      negative margins but associated with significant surgical morbidity. Observation
      was included as an option for patients with resectable desmoid tumors that are
      small and asymptomatic, not causing morbidity, pain, or functional limitation.
      Sorafenib is included as an option for systemic therapy for patients with desmoid
      tumors.

PMID- 22878821
TI  - Current approaches in hereditary nonpolyposis colorectal cancer.
AB  - This article emphasizes the central role of tumor-based testing for
      microsatellite instability followed by performance of genetic counselor-driven
      germline mutation testing in hereditary nonpolyposis colorectal cancer (HNPCC).
      Suitably aggressive colorectal neoplasm surveillance is shown to be critical.
      Limitations of the evidentiary base for extracolonic screening are conceded, with
      some cautious suggestions for possible strategies notwithstanding the lack of
      data. Advances in chemoprevention have been made in both familial adenomatous
      polyposis (clinical trial data favoring eicosapentaenoic acid) and HNPCC
      (controversial aspirin data). For various reasons, however, no agent or
      combination of agents has yet come into routine use in either condition, with
      further trials underway or being designed for both conditions.

PMID- 22878822
TI  - Influential factors for post-fellowship career decision-making: an NCCN survey.
AB  - Insight into factors important to fellows' decision-making about their career
      paths is critical to successfully developing program curricula, making capacity
      projections, and recruiting oncology physicians. This study was performed to
      determine the factors associated with post-fellowship career decision-making.
      Program evaluation surveys were administered to oncology fellows who attended the
      Fellows Recognition Program at the 2009 NCCN Annual Conference. A total of 125
      (75%) fellows completed the initial survey. Overall, 73% of fellows reported
      participating in clinical research and 58% received formal training as part of
      their fellowship program. Receipt of formal training was correlated with greater
      program satisfaction (r(s) = 0.20; P = .03), feeling more prepared for a post
      fellowship career (r(s) = 0.30; P < .001), and greater interest in clinical
      research post fellowship (r(s) = 0.32; P < .001). Interest in post-fellowship
      clinical research (r(s) = 0.49; P < .001) and importance of protected academic
      time (r(s) = 0.57; P < .001) were strongly correlated with interest in practicing
      in an academic environment, whereas institutional reputation (r(s) = 0.18; P =
      .04) and a multidisciplinary practice environment (r(s) = 0.22; P = .02) were
      moderately associated with interest. Location, salary, multidisciplinary
      environment, and flexible scheduling were the most important controllable
      lifestyle (CL) factors. These results suggest that fellowship programs may be
      able to foster a desire to participate in research and subsequent interest in
      practicing in an academic institution through providing opportunities for formal
      training in clinical research skills. However, even in an academic setting, CL
      factors are important to attracting and retaining faculty.

PMID- 22878824
TI  - NCCN Clinical Practice Guidelines Acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) remains the most common form of acute leukemia among
      adults and accounts for the largest number of annual deaths due to leukemias in
      the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN
      Guidelines) for AML provide recommendations on the diagnostic evaluation and
      workup for AML, risk assessment based on cytogenetic and molecular features,
      treatment options for induction and consolidation therapies for younger and older
      (age >= 65 years) adult patients, and key supportive care considerations.

PMID- 22878823
TI  - Optimal management of malignant pleural effusions (results of CALGB 30102).
AB  - The optimal strategy to achieve palliation of malignant pleural effusions (MPEs)
      is unknown. This multi-institutional, prospective, randomized trial compares 2
      established methods for controlling symptomatic unilateral MPEs. Patients with
      unilateral MPEs were randomized to either daily tunneled catheter drainage (TCD)
      or bedside talc pleurodesis (TP). This trial is patterned after a previous
      randomized trial that showed that bedside TP was equivalent to thoracoscopic TP
      (CALGB 9334). The primary end point of the current study was combined success:
      consistent/reliable drainage/pleurodesis, lung expansion, and 30-day survival. A
      secondary end point, survival with effusion control, was added retrospectively.
      This trial randomized 57 patients who were similar in terms of age (62 years),
      active chemotherapy (28%), and histologic diagnosis (lung, 63%; breast, 12%;
      other/unknown cancers, 25%) to either bedside TP or TCD. Combined success was
      higher with TCD (62%) than with TP (46%; odds ratio, 5.0; P = .064). Multivariate
      regression analysis revealed that patients treated with TCD had better 30-day
      activity without dyspnea scores (8.7 vs. 5.9; P = .036), especially in the
      subgroup with impaired expansion (9.1 vs. 4.6; P = .042). Patients who underwent
      TCD had better survival with effusion control at 30 days compared with those who
      underwent TP (82% vs. 52%, respectively; P = .024). In this prospective
      randomized trial, TCD achieved superior palliation of unilateral MPEs than TP,
      particularly in patients with trapped lungs.

PMID- 22878825
TI  - Who benefits from maintenance therapy in acute promyelocytic leukemia?
AB  - Acute promyelocytic leukemia (APL) is remarkable for its upfront mortality rate
      from disseminated intravascular coagulation and its high cure rate with therapy.
      Although induction and consolidation regimens continue to evolve, newer
      approaches combine an anthracycline with or without cytarabine and the highly
      effective differentiating drugs all-trans retinoic acid and arsenic trioxide.
      Early trials showed a benefit of maintenance therapy on overall survival,
      although this benefit has been less clear in subsequent trials. This review
      assesses the differences in these trials and outlines a rational approach to
      maintenance therapy in APL, generally advising against maintenance in patients
      who underwent adequate consolidation therapy, particularly if they presented with
      low-risk disease (WBC < 10,000) and experienced molecular complete remission
      after completion of consolidation.

PMID- 22878826
TI  - Monitoring minimal residual disease in acute myeloid leukemia: ready for prime
      time?
AB  - Predicting the outcome of therapy in patients with acute myeloid leukemia (AML)
      is currently necessary for making treatment decisions. Pretreatment covariates,
      such as clinical and molecular predictors, have helped identify which patients
      are more or less likely to survive their disease using the currently available
      regimens. Progress in establishing optimized flow cytometry and quantitative
      polymerase chain reaction assays for detecting minimal residual leukemia has
      provided new potential tools for predicting outcome. However, the most important
      next step in using these techniques toward personalized treatment of AML would be
      developing effective and safe strategies for eradicating the residual leukemic
      cells that are likely chemoresistant. With further refinement and standardization
      of the assays, and the development of novel, effective, and molecularly targeted
      agents, monitoring of minimal residual disease is likely to be incorporated into
      AML guidelines.

PMID- 22878827
TI  - Managing the financial impact of cancer treatment: the role of clinical practice
      guidelines.

PMID- 22878829
TI  - Intake of fermented beverages protect against acute myocardial injury: target
      organ cardiac effects and vasculoprotective effects.
AB  - Mild-to-moderate alcohol consumption has been associated with reduced risk of
      morbi/mortality from coronary artery disease. However, whether beer intake
      affords cardioprotection remains unclear. We investigated whether beer intake
      (alcohol-containing and alcohol-free brew) provides cardioprotection in a pig
      model of myocardial infarction (MI). Pigs were randomly assigned to: (1) be fed
      for 10 days a high-cholesterol diet (HC); (2) HC + low-dose beer (LB; 12.5 g
      alcohol/day); (3) HC + moderate-dose beer (MB; 25 g alcohol/day); or IV) HC +
      alcohol-free-MB (0.0 g alcohol/day) before MI induction and kept 21 days with the
      same regime. Scar size, echocardiography, biochemical and oxidative parameters
      were assessed. Myocardial tissue was obtained for molecular analysis and
      histology. All beer-fed animals were less prone to arrhythmogenesis during
      ischemia. At sacrifice, beer intake was associated with lower oxidative stress
      and higher HDL-antioxidant capacity. Within the ischemic myocardium beer-fed
      animals showed higher Akt/eNOS and AMPK activation and reduced sirtuin1-related
      apoptosis. Compared to controls beer intake was associated with lower lipid
      infiltration, higher TGFbeta-related collagen fibril formation and diminished
      MMP9 activity in the fibrous tissue limiting scar size (HC + LB and HC + MB P <
      0.05 and HC + alcohol-free-MB P = 0.068 vs. HC). Systolic-related parameters were
      similarly worsen post-MI in all groups and further deteriorated in control
      animals (P <= 0.05 vs. post-MI). At sacrifice, all animals showed a worsening in
      diastolic-related parameters but overall cardiac performance was improved in beer
      fed animals regardless of the dose or alcohol content (P <= 0.05). In conclusion,
      beer intake reduces oxidative stress and apoptosis, activates RISK components and
      favors reparative fibrosis improving global cardiac performance.

PMID- 22878830
TI  - A statistical framework for inter-group image registration.
AB  - Groupwise image registration plays an important role in medical image analysis.
      The principle of groupwise image registration is to align a given set of images
      to a hidden template space in an iteratively manner without explicitly selecting
      any individual image as the template. Although many approaches have been proposed
      to address the groupwise image registration problem for registering a single
      group of images, few attentions and efforts have been paid to the registration
      problem between two or more different groups of images. In this paper, we propose
      a statistical framework to address the registration problems between two
      different image groups. The main contributions of this paper lie in the following
      aspects: (1) In this paper, we demonstrate that directly registering the group
      mean images estimated from two different image groups is not sufficient to
      establish the reliable transformation from one image group to the other image
      group. (2) A novel statistical framework is proposed to extract anatomical
      features from the white matter, gray matter and cerebrospinal fluid tissue maps
      of all aligned images as morphological signatures for each voxel. The extracted
      features provide much richer anatomical information than the voxel intensity of
      the group mean image, and can be integrated with the multi-channel Demons
      registration algorithm to perform the registration process. (3) The proposed
      method has been extensively evaluated on two publicly available brain MRI
      databases: the LONI LPBA40 and the IXI databases, and it is also compared with a
      conventional inter-group image registration approach which directly performs
      deformable registration between the group mean images of two image groups.
      Experimental results show that the proposed method consistently achieves higher
      registration accuracy than the method under comparison.

PMID- 22878831
TI  - Alcohol and smoking consumption behaviours in older Australian adults:
      prevalence, period and socio-demographic differentials in the DYNOPTA sample.
AB  - PURPOSE: Alcohol consumption and tobacco use are key risk factors for chronic
      disease and health burden across the adult lifespan. We estimate the prevalence
      of alcohol consumption and smoking by age and time period in adults from mid to
      old age. METHODS: Participants (n = 50,652) were drawn from the Dynamic Analyses
      to Optimise Ageing (DYNOPTA) project and were compared with Australian National
      Health Survey data. Alcohol and smoking consumption DYNOPTA data were weighted to
      the estimated resident population of the sampling frame for each contributing
      study according to age and sex distributions within major statistical regions.
      RESULTS: Comparisons in the rates of smoking and alcohol consumption between
      DYNOPTA and other national surveys were comparable. Males were more likely to be
      (RRR = 2.12) or have been smokers (RRR = 2.97), whilst females were more likely
      to be non-drinkers (RRR = 2.52). Period effects were also identified; higher
      prevalence rates in consumption of alcohol (RRR = 3.21) and smoking (RRR = 1.67)
      for those contributing studies from the early 1990's, in comparison with those
      studies from the latter half of the decade, were reported. CONCLUSIONS: Over a
      decade, prevalence rates for high-risk consumption of alcohol and current smoking
      behaviour declined and suggest the possible impact of government health policy,
      with targeted-health policies, that included bans on public smoking, and a
      toughening of legislation against alcohol-related crime.

PMID- 22878832
TI  - The course of posttraumatic stress symptoms and functional impairment following a
      disaster: what is the lasting influence of acute versus ongoing traumatic events
      and stressors?
AB  - PURPOSE: Ongoing traumatic events and stressors, rather than acute sources of
      trauma, may shape long-term post-disaster mental health. The purpose of this
      study was to compare the influence of acute hurricane-related exposures and
      ongoing post-hurricane exposures on the short- and long-term course of
      posttraumatic stress symptoms (PTSS) and functional impairment (FI). METHODS: A
      random sample of adults (n = 658) in Galveston and Chambers Counties, Texas, was
      selected 2-6 months after Hurricane Ike and interviewed 3 times over 18 months.
      Hurricane-related exposures included traumatic events such as death of a family
      member due to the hurricane and stressors such as loss/damage to personal
      property due to the hurricane. Post-hurricane exposures included traumatic events
      such as sexual assault and stressors such as divorce or serious financial
      problems. RESULTS: Experiencing an acute hurricane-related traumatic event or
      stressor was associated with initial post-hurricane PTSS [RR = 1.92 (95% CI =
      1.13-3.26) and RR = 1.62 (1.36-1.94), respectively] and FI [RR = 1.76; (1.05
      2.97) and RR = 1.74 (1.46-2.08)], respectively, and acute hurricane-related
      stressors were associated with a higher rate of increase in FI over time [RR =
      1.09; (1.01-1.19)]. In contrast, ongoing post-hurricane daily stressors were not
      associated within initial PTSS and FI, but were associated with PTSS and FI at
      the second and third interviews. CONCLUSIONS: While immediate postdisaster
      interventions may influence short-term mental health, investment in the
      prevention of ongoing stressors may be instrumental to manage long-term mental
      health status.

PMID- 22878833
TI  - Suicide and media reporting: a longitudinal and spatial analysis.
AB  - PURPOSE: The impact of media reporting on copycat suicides has been well
      established in various cases of celebrity suicide. However, knowledge is limited
      about the spatial and temporal relationship between suicide death and media
      reporting over a long period of time. This study investigated the association of
      suicide deaths with suicide news in longitudinal and spatial dimensions. METHODS:
      All suicides during 2003-2010 (n = 31,364) were included. Suicide news in the
      study period was retrieved from Google News, and included all available news
      media in Taiwan. Empirical mode decomposition was used to identify the main
      intrinsic oscillation, reflecting both major and minor suicide events, and time
      dependent intrinsic correlation was used to quantify the temporal correlation
      between suicide deaths and suicide news. RESULTS: The media reporting of suicide
      was synchronized with increased suicide deaths during major suicide events such
      as celebrity death, and slightly lagged behind the suicide deaths for 1 month in
      other periods without notable celebrity deaths. The means of suicide reported in
      the media diversely affected the suicide models. Reports of charcoal burning
      suicide exhibited an exclusive copycat effect on actual charcoal burning deaths,
      whereas media reports of jumping had a wide association with various suicide
      models. Media reports of suicide had a higher association with suicide deaths in
      urban than in rural areas. CONCLUSIONS: This report suggested that a delayed
      effect of copycat suicide may exist in media reports of minor suicide events. The
      competitive reporting of minor suicide events must be avoided and addressed by
      media professionals.

PMID- 22878834
TI  - Training for linear endobronchial ultrasound among US pulmonary/critical care
      fellowships: a survey of fellowship directors.
AB  - BACKGROUND: Endobronchial ultrasound (EBUS) has revolutionized the ability of
      bronchoscopists to visualize and sample structures surrounding the
      tracheobronchial tree. It has been shown to be safe, minimally invasive, and
      highly accurate in the staging and diagnosing of mediastinal diseases. A prior
      survey of pulmonary fellowship program directors conducted in 2004 showed that
      only 2% of programs offered EBUS training. METHODS: Surveys were mailed to 154
      pulmonary/critical care fellowship directors in the United States and Puerto
      Rico. Demographics of the fellowship and details of EBUS training were recorded.
      A comparison of EBUS volume was made between programs with and without an
      identifiable interventional pulmonologist (IP). RESULTS: The survey response rate
      was 71%. EBUS equipment was available at 89% of programs. Of those without EBUS,
      100% expressed the goal of obtaining equipment within the year. An identifiable
      IP was present in 70% of programs. This was associated with more EBUS procedures
      performed by trainees ( P , .01). Only 30% of programs have a formal protocol in
      place to evaluate EBUS competency. Conventional transbronchial needle aspiration
      is routinely taught in 89% of fellowship programs. CONCLUSIONS: EBUS exposure has
      rapidly disseminated into fellowship training programs, and programs with an
      identifiable IP are more likely to provide fellows with more EBUS procedures. The
      findings of this survey point out the need to develop a standardized protocol for
      EBUS competency that includes current recommendations and may require training
      with simulation.

PMID- 22878835
TI  - Assessing anomalous perceptual experiences in nonpsychiatric individuals and
      outpatients with psychosis in Taiwan: an investigation using the cardiff
      anomalous perceptions scale (CAPS).
AB  - The Cardiff anomalous perceptions scale (CAPS) has been recently designed for the
      assessment of anomalous perceptual experiences in the general population, and
      includes dimensions that measure distress, intrusiveness, and frequency. The
      purpose of this study was to assess the psychometric properties of a Taiwanese
      version of the CAPS. The English version of the CAPS was translated into
      Taiwanese (CAPS-T) and the latter was applied to this study. We administered the
      questionnaire to a consecutive sample of 192 participants with (n = 106; clinical
      group including schizophrenia and affective psychosis) or without psychotic
      disorders (n = 86; non-clinical group). In addition to the CAPS-T, the Taiwanese
      version of the brief psychiatric symptom rating scale (BSRS) measured the
      severity of the psychopathology. We also tested the psychometric properties of
      the CAPS-T including construct validity, internal consistency, test-retest
      reliability, and convergent and discriminative validity. Overall, the CAPS-T
      showed good construct validity, internal consistency, and stability over time and
      correlated significantly with the psychoticism subscale of the BSRS. As
      predicted, the mean differences in CAPS-T scores between participants with or
      without a psychotic disorder were significant. Convergent and discriminative
      validity were satisfactory. A score of 5 was found to the best threshold in
      discriminating between clinical and non-clinical samples. Our findings indicate
      that the Taiwanese version of the CAPS is a reliable and valid instrument to
      measure the multidimensionality of perceptual anomalies in general and appears to
      complement the clinical measures of psychosis proneness in Taiwan.

PMID- 22878836
TI  - Role of endoscopic retrograde pancreatography for early detection of pancreatic
      ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm of
      the pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is
      often found with distinct pancreatic ductal adenocarcinoma (PDAC) in the same
      pancreas. The aim of this study was to clarify whether endoscopic retrograde
      pancreatography (ERP) would be useful for the early detection of concomitant
      PDACs in patients with IPMNs. METHODS: Medical records of 179 patients who were
      histologically confirmed to have IPMNs after resection between 1987 and 2011 were
      reviewed. The patients having concomitant PDACs were selected, and the diagnostic
      abilities to detect concomitant PDACs of computed tomography (CT), magnetic
      resonance imaging (MRI), endoscopic ultrasonography (EUS), and ERP were compared
      between early (stages 0-I according to Japanese General Rules for Pancreatic
      Cancer) and advanced (stages II-IV) PDACs. RESULTS: A total of 23 PDACs developed
      synchronously or metachronously in 20 patients, and the prevalence of PDACs
      concomitant with IPMNs was 11.2 % (20/179). Sensitivities of CT (16 vs. 87 %),
      MRI (29 vs. 93 %), and EUS (29 vs. 92 %) in the early group were significantly
      lower than those in the advanced group (p < 0.01). On the other hand, the
      sensitivity of ERP in the early group was as high as that in the advanced group
      (86 vs. 82 %, respectively, p > 0.99). Among 7 early PDACs, 3 were diagnosed only
      by ERP. CONCLUSIONS: ERP has an important role in the early diagnosis of distinct
      PDACs in patients with IPMNs. Further investigation is necessary to clarify the
      indication and the timing of ERP during management of IPMNs in term of early
      detection of concomitant PDACs.

PMID- 22878837
TI  - A novel concept of identifying precancerous cells to enhance anti-cancer
      therapies.
AB  - Cancer is the leading cause of death worldwide and mortality due to cancer
      continues to rise. Cancer cell resistance to chemoradiotherapy is hindering
      treatment efforts in clinics. Prevention strategies and early detection thus may
      reduce mortality. In this study, we have proposed the concept of using
      precancerous cells and their progeny in cancer therapy, which could provide
      unique insights for early cancer diagnosis, treatment, and preventive therapy. In
      addition to discussing the nature and characteristics of precancerous cells and
      their progeny, we have also introduced an effective precancerous cell-targeted
      therapy based on an animal model of hepatocellular carcinoma. Anti-precancerous
      cell drug development should be a major target during cancer elimination and it
      may lead to preventive therapies for individuals with a high risk of developing
      cancer.

PMID- 22878838
TI  - Pancreatic cancer stem cells: regulatory networks in the tumor microenvironment
      and targeted therapy.
AB  - Recent evidence has demonstrated that the existence of a cancer stem cell (CSC)
      subset in a solid tumor is responsible for the progression and relapse of cancer
      as well as its resistance to current therapies. Over the past decade, CSC
      research on pancreatic cancer has progressed. A fundamental understanding of
      pancreatic CSCs may improve therapies and deepen insight into the role of cell
      cell interactions within a tumor microenvironment in pancreatic cancer
      progression. This review focuses on the impact of pancreatic CSCs on the
      regulatory networks in the tumor microenvironment, and the implications of
      targeting CSCs to treat pancreatic cancer.

PMID- 22878839
TI  - Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related
      to celiac disease? A proof-of-concept study.
AB  - PURPOSE: Celiac disease is an autoimmune-mediated enteropathy characterized by
      adaptive and innate immune responses to dietary gluten in wheat, rye and barley
      in genetically susceptible individuals. Gluten-derived gliadin peptides are
      deamidated by transglutaminase 2 (TG2), leading to an immune response in the
      small-intestinal mucosa. TG2 inhibitors have therefore been suggested as putative
      drugs for celiac disease. In this proof-of-concept study we investigated whether
      two TG2 inhibitors, cell-impermeable R281 and cell-permeable R283, can prevent
      the toxic effects of gliadin in vitro and ex vivo. METHODS: Intestinal epithelial
      Caco-2 cells were treated with peptic-tryptic-digested gliadin (PT-gliadin) with
      or without TG2 inhibitors and thereafter direct toxic effects (transepithelial
      resistance, cytoskeletal rearrangement, junction protein expression and
      phoshorylation of extracellular-signal-regulated kinase 1/2) were determined. In
      an organ culture of celiac-patient-derived small-intestinal biopsies we measured
      secretion of TG2-autoantibodies into the culture medium and the densities of CD25
      and interleukin (IL) 15-positive cells, forkhead box P3 (FOXP3)-positive
      regulatory T cells (Tregs) and Ki-67-positive proliferating crypt cells. RESULTS:
      Both TG2 inhibitors evinced protective effects against gliadin-induced
      detrimental effects in Caco-2 cells but the cell-impermeable R281 seemed slightly
      more potent. In addition, TG2 inhibitor R281 modified the gluten-induced increase
      in CD25- and IL15-positive cells, Tregs and crypt cell proliferation, but had no
      effect on antibody secretion in celiac-patient-derived biopsies. CONCLUSIONS: Our
      results suggest that TG2 inhibitors are able to reduce certain gliadin-induced
      effects related to responses in vitro and ex vivo.

PMID- 22878840
TI  - Preface: Immunological tango in Barcelona 2011.

PMID- 22878842
TI  - Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as
      determined by isothermal microcalorimetry.
AB  - The strong toxicity of pathogenic bacteria has resulted in high levels of
      morbidity and mortality in the general population. Developing effective
      antibacterial agents with high efficacy and long activity is in great demand. In
      this study, the microcalorimetric technique based on heat output of bacterial
      metabolism was applied to evaluate the effect of berberine on Escherichia coli,
      Bacillus subtilis, individually and in a mixture of both using a multi-channel
      microcalorimeter. The differences in shape of the power-time fingerprints and
      thermokinetic parameters of microorganism growth were compared. The results
      revealed that low concentration (20 MUg/mL) of berberine began to inhibit the
      growth of E. coli and mixed microorganisms, while promoting the growth of B.
      subtilis; high concentration of berberine (over 100 MUg/mL) inhibited B.
      subtilis. The endurance of E. coli to berberine was obviously lower than B.
      subtilis, and E. coli could decrease the endurance of B. subtilis to berberine.
      The sequence of half-inhibitory concentration (IC(50)) of berberine was: B.
      subtilis (952.37 MUg/mL) > mixed microorganisms (682.47 MUg/mL) > E. coli (581.69
      MUg/mL). Berberine might be a good selection of antibacterial agent used in the
      future. The microcalorimetric method should be strongly suggested in screening
      novel antibacterial agents for fighting against pathogenic bacteria.

PMID- 22878841
TI  - Human chitotriosidase: a sensitive biomarker of sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown
      etiology. No suitable biomarkers are available to evaluate the evolution of this
      disease, which still has an unpredictable clinical course. Some years ago our
      research group proposed chitotriosidase as a potential biomarker with prognostic
      value, that however needed to be validated. AIMS AND METHODS: The aims of this
      study were to evaluate the sensitivity and specificity of chitotriosidase in a
      population of 232 sarcoidosis patients under the observation of our Sarcoidosis
      Regional Referral Centre in Siena and to analyse enzyme concentrations in
      different disease phenotypes (as defined by the recently published COS
      classification) to define its prognostic value. RESULTS: Serum chitotriosidase
      concentrations were significantly higher in patients than in healthy controls
      (p<0.0001) and were directly correlated with ACE levels (r=0.25, p<0.0001). ROC
      curve analysis revealed 88.6 % sensitivity and 92.8 % specificity. Enzyme
      concentrations were significantly higher in stage 3 sarcoidosis than in stage 0
      (p=0.02). The lowest concentrations of chitotriosidase were found in untreated
      patients in remission (COS-1), while the highest enzyme concentrations were found
      in symptomatic patients with persistent disease on steroids and with functional
      deterioration in the last year (COS-9). In COS-9 subgroup, chitotriosidase
      decreased significantly after the increasing of steroid dose or the introduction
      of a new immunosuppressant therapy (p<0.01). CONCLUSION: Chitotriosidase proved
      to be a biomarker with good sensitivity and specificity that is easily detected
      in serum. It can be proposed in clinical practice to identify progressive
      patients requiring close follow-up, to detect relapses and to evaluate the
      effects of therapy.

PMID- 22878843
TI  - Features and applications of bilirubin oxidases.
AB  - Discovered in 1981 by Tanaka and Murao (Agric Biol Chem 45:2383-2384, 1981),
      bilirubin oxidase (BOD) is a sub-group of multicopper oxidases (MCOs) also
      utilizing four Cu(+/2+) ions. It catalyzes the oxidation of bilirubin to
      biliverdin, hence the classification of bilirubin oxidase, and has been primarily
      used in the determination of bilirubin in serum and thereby in the diagnostic of
      jaundice. Unlike laccases, the most studied MCOs, BODs display a high activity
      and stability at neutral pH, a high tolerance towards chloride anions and other
      chelators, and for some species, a high thermal tolerance. Therefore, BODs could
      potentially be an alternative to laccase which are so far mainly restricted to
      applications in acid media. Because of growing interest in BODs for numerous
      applications under mild pH conditions, based on the number of patents and
      publications published in the last 5 years, here I will summarize the available
      data on the biochemical properties of BODs, their occurrence, and their possible
      biotechnological use in (1) the field of Healthcare for the elaboration of
      biofuel cells or bilirubin sensors or (2) the field of environmentally desirable
      applications such as depollution, decolorization of dyes, and pulp bleaching.

PMID- 22878844
TI  - Alginate synthesis in Azotobacter vinelandii is increased by reducing the
      intracellular production of ubiquinone.
AB  - Azotobacter vinelandii, a soil nitrogen fixing bacterium, produces alginate a
      polysaccharide with industrial and medical relevant applications. In this work,
      we characterized a miniTn5 mutant, named GG101, that showed a 14-fold increase in
      the specific production of alginate when grown diazotrophically on solid minimal
      medium comparing to the parental E strain (also named AEIV). Quantitative real
      time reverse transcription PCR analysis indicated that this increased alginate
      production was due to higher expression levels of several biosynthetic alg genes
      such as algD. Sequencing of the locus interrupted in GG101 indicated that the
      miniTn5 was inserted in the positive strand, and 10 bp upstream the start codon
      of the gene ubiA, encoding the enzyme for the second step in the biosynthesis of
      ubiquinone (Q8). Both the transcription of ubiA and the content of Q8 are
      decreased in the mutant GG101 when compared to the wild-type strain E. Genetic
      complementation of mutant GG101 with a wild-type copy of the ubiCA genes restored
      the content of Q8 and reduced the production of alginate to levels similar to
      those of the parental E strain. Furthermore, respirometric analysis showed a
      reproducible decrease of about 8 % in the respiratory capacity of mutant GG101,
      at exponential phase of growth in liquid minimal medium. Collectively, our data
      show that a decreased content in Q8 results in higher levels of alginate in A.
      vinelandii.

PMID- 22878845
TI  - An FMRI investigation of the cortical network underlying detection and
      categorization abilities in hemianopic patients.
AB  - The current study aims to investigate visual scene perception and its neuro
      anatomical correlates for stimuli presented in the central visual field of
      patients with homonymous hemianopia, and thereby to assess the effect of a right
      or a left occipital lesion on brain reorganization. Fourteen healthy
      participants, three left brain damaged (LBD) patients with right homonymous
      hemianopia and five right brain damaged (RBD) patients with left homonymous
      hemianopia performed a visual detection task (i.e. "Is there an image on the
      screen?") and a categorization task (i.e. "Is it an image of a highway or a
      city?") during a block-designed functional magnetic resonance imaging recording
      session. Cerebral activity analyses of the posterior areas-the occipital lobe in
      particular-highlighted bi-hemispheric activation during the detection task but
      more lateralized, left occipital lobe activation during the categorization task
      in healthy participants. Conversely, in patients, the same network of activity
      was observed in both tasks. However, LBD patients showed a predominant activation
      in their right hemisphere (occipital lobe and posterior temporal areas) whereas
      RBD patients showed a more bilateral activation (in the occipital lobes).
      Overall, our preliminary findings suggest a specific pattern of cerebral
      activation depending on the task instruction in healthy participants and cerebral
      reorganization of the posterior areas following brain injury in hemianopic
      patients which could depend upon the side of the occipital lesion.

PMID- 22878846
TI  - Estrogen attenuates manganese-induced glutamate transporter impairment in rat
      primary astrocytes.
AB  - The astrocytic glutamate transporters (GLT-1, GLAST) are critical for removing
      excess glutamate from synaptic sites, thereby maintaining glutamate homeostasis
      within the brain. 17beta-Estradiol (E2) is one of the most active estrogen
      hormones possessing neuroprotective effects both in in vivo and in vitro models,
      and it has been shown to enhance astrocytic glutamate transporter function (Liang
      et al. in J Neurochem 80:807-814, 2002; Pawlak et al. in Brain Res Mol Brain Res
      138:1-7, 2005). However, E2 is not clinically optimal for neuroprotection given
      its peripheral feminizing and proliferative effects; therefore, brain selective
      estrogen receptor modulators (neuro SERMs) (Zhao et al. in Neuroscience 132:299
      311, 2005) that specifically target estrogenic mechanisms, but lack the systemic
      estrogen side effects offer more promising therapeutic modality for the treatment
      of conditions associated with excessive synaptic glutamate levels. This review
      highlights recent studies from our laboratory showing that E2 and SERMs
      effectively reverse glutamate transport inhibition in a manganese (Mn)-induced
      model of glutamatergic deregulation. Specifically, we discuss mechanisms by which
      E2 restores the expression and activity of glutamate uptake. We advance the
      hypothesis that E2 and related compounds, such as tamoxifen may offer a potential
      therapeutic modality in neurodegenerative disorders, which are characterized by
      altered glutamate homeostasis.

PMID- 22878848
TI  - Asthma beliefs are associated with medication adherence in older asthmatics.
AB  - BACKGROUND: Empirical research and health policies on asthma have focused on
      children and young adults, even though asthma morbidity and mortality are higher
      among older asthmatics. OBJECTIVE: To explore the relationship of asthma-related
      beliefs and self-reported controller medication adherence in older asthmatics.
      DESIGN: An observational study of asthma beliefs and self-management among older
      adults. PARTICIPANTS: Asthmatics ages >= 60 years (N = 324, mean age 67.4 +/-
      6.8, 28 % white, 32 % black, 30 % Hispanic) were recruited from primary care
      practices in New York City and Chicago. MAIN MEASURES: Self-reported controller
      medication adherence was assessed using the Medication Adherence Report Scale.
      Based on the Common Sense Model of Self-Regulation, patients were asked if they
      believe they only have asthma with symptoms, their physician can cure their
      asthma, and if their asthma will persist. Beliefs on the benefit, necessity and
      concerns of treatment use were also assessed. Multivariate logistic regression
      was used to examine the association of beliefs with self-reported medication
      adherence. KEY RESULTS: The majority (57.0 %) of patients reported poor
      adherence. Poor self-reported adherence was more common among those with
      erroneous beliefs about asthma illness and treatments, including the "no
      symptoms, no asthma" belief (58.7 % vs. 31.7 %, respectively, p < 0.001), "will
      not always have asthma" belief (34.8 % vs. 12.5 %, p < 0.001), and the "MD can
      cure asthma" belief (21.7 % vs. 9.6 %, p = 0.01). Adjusting for illness beliefs,
      treatment beliefs and demographics, patients with a "no symptoms, no asthma"
      belief had lower odds of having good self-reported adherence (odds ratio [OR]
      0.45, 95 % confidence interval [CI] 0.23-0.86), as did those with negative
      beliefs about the benefits (OR 0.73, 95 % CI 0.57-0.94) and necessity (OR 0.89,
      95 % CI 0.83-0.96) of treatment. CONCLUSIONS: Illness and treatment beliefs have
      a strong influence on self-reported medication adherence in older asthmatics.
      Interventions to improve medication adherence in older asthmatics by modifying
      illness and treatment beliefs warrant study.

PMID- 22878849
TI  - Calciphylaxis: severe calcification of the arteries.

PMID- 22878850
TI  - Facial flushing with food: the auriculotemporal syndrome.

PMID- 22878851
TI  - Implementation of Physician Orders for Life Sustaining Treatment in nursing homes
      in California: evaluation of a novel statewide dissemination mechanism.
AB  - BACKGROUND: Implementing Physician Orders for Life Sustaining Treatment (POLST)
      forms aims to improve communication of life-sustaining treatment preferences
      across care venues. California enabled this clinical tool in 2009, and a novel
      intervention of community coalitions was undertaken to advance POLST in
      localities around the state. Coalitions engaged facilities, including nursing
      homes (NHs), to foster POLST adoption. Eighteen months after introduction of
      POLST, we studied POLST implementation in California NHs. METHODS: NHs randomly
      selected in coalition and non-coalition areas were mailed surveys about POLST
      preparation and use in 2010. Coalitions identified which NHs they worked with.
      RESULTS: Of 546 NHs surveyed, 143 (52 %) in coalition areas and 141 (52 %) in non
      coalition areas responded. In 82 % of responding NHs, staff received POLST
      education and 59 % of NHs reported having a formal policy on handling POLST. Two
      thirds of NHs had admitted a resident with a POLST, and 15 % of newly admitted
      residents over the past month had a POLST (range 0-100 %). Eighty-one percent of
      NHs had completed a POLST with a resident. Fifty-four percent of residents were
      estimated to have a POLST (range 0-100 %) (coalition area NHs 60 % vs. non-
      coalition area NHs 48 %, p = 0.02). Within coalition areas, NHs that had worked
      with coalitions were more likely to have completed a POLST with a resident after
      admission than NHs that had not worked with coalitions. Few NHs (7 %) reported
      difficulty following POLST orders, but 38 % noted difficulty involving physicians
      in POLST completion. CONCLUSION: Less than 2 years after introduction, many
      California nursing homes report using POLST, although some NHs reported no
      experience. A novel community coalition intervention facilitated POLST
      implementation.

PMID- 22878852
TI  - Hematocrit effect in bilateral subdural hematomas.

PMID- 22878853
TI  - More than skin deep.

PMID- 22878854
TI  - How much is lost in using single items?

PMID- 22878855
TI  - Hypertension and hydronephrosis: rapid resolution of high blood pressure
      following relief of bilateral ureteric obstruction.
AB  - Hypertension secondary to hydronephrosis is not commonly reported in the medical
      literature. Tubuloglomerular feedback and the renin-angiotensin-aldosterone axis
      are thought to mediate this process. We describe a patient presenting with acute
      kidney injury and bilateral hydronephrosis secondary to pelvic malignancy in
      which peripheral venous renin and aldosterone were elevated. Her blood pressure
      improved rapidly following insertion of bilateral nephrostomies. The speed of
      resolution of hypertension following relief of obstruction suggests that
      humorally mediated vasoconstriction can play an important role in the mechanism
      by which hydronephrosis causes hypertension. We also discuss other causes of
      renal parenchymal compression that may lead to the development of hypertension.

PMID- 22878856
TI  - Counting quality, not hours: understanding the impact of duty hour reform on
      internal medicine residency education.

PMID- 22878858
TI  - All in a day's work: establishing rapport, making decisions, reducing
      disparities.

PMID- 22878857
TI  - Pain adversely affects outcomes to a collaborative care intervention for anxiety
      in primary care.
AB  - BACKGROUND: Primary care patients with Panic Disorder (PD) and Generalized
      Anxiety Disorder (GAD) experience poorer than expected clinical outcomes, despite
      the availability of efficacious pharmacologic and non-pharmacologic treatments. A
      barrier to recovery from PD/GAD may be the co-occurrence of pain. OBJECTIVE: To
      evaluate whether pain intensity interfered with treatment response for PD and/or
      GAD in primary care patients who had received collaborative care for anxiety
      disorders. DESIGN: A secondary data analysis of a randomized, controlled
      effectiveness trial comparing a telephone-delivered collaborative care
      intervention for primary care patients with severe PD and/or GAD to their
      doctor's "usual" care. PARTICIPANTS: Patients had to have a diagnosis of PD
      and/or GAD and a severe level of anxiety symptoms. The 124 patients randomized at
      baseline to the collaborative care intervention were analyzed. Participants were
      divided into two pain intensity groups based on their response to the SF-36
      Bodily Pain scale (none or mild pain vs. at least moderate pain). MAIN MEASURES:
      Pain was assessed using the Bodily Pain scale of the SF-36. Anxiety symptoms were
      measured with the Hamilton Anxiety Rating Scale (HRS-A), Panic Disorder Severity
      Scale (PDSS) and Generalized Anxiety Disorder Severity Scale (GADSS). Measures
      were collected over 12 months. KEY RESULTS: At baseline, patients with at least
      moderate pain were significantly more likely to endorse more anxiety symptoms on
      the HRS-A than patients with no pain or mild pain (P < .001). Among patients with
      severe anxiety symptoms, 65 % (80/124) endorsed experiencing at least moderate
      pain in the previous month. A significantly lesser number of patients achieved a
      50 % improvement at 12 months on the HRS-A and GADSS if they had at least
      moderate pain as compared to patients with little or no pain (P = 0.01 and P =
      0.04, respectively). CONCLUSIONS: Coexisting pain was common in a sample of
      primary care patients with severe PD/GAD, and appeared to negatively affect
      response to anxiety treatment.

PMID- 22878859
TI  - Advance care planning safeguards.

PMID- 22878861
TI  - A comparative study of semi-squaraine and squaraine dyes using computational
      techniques: tuning the charge transfer/biradicaloid character by substitution.
AB  - Semi-squaraines (SMSQ) are known as donor-acceptor (D-A) type molecules whereas
      squaraines (SQ), which differs from SMSQ by an extra donor group, are more or
      less biradicaloids in nature. The effect of the additional donor group in SQ,
      which changes the nature of the molecule, on geometrical and electronic structure
      are studied here and compared with the corresponding SMSQ. It is noticed from the
      geometrical parameters that, a strong resonance exists in SQ whereas disparity in
      carbon-carbon bond lengths of central C4 ring is seen in SMSQ dyes. The
      increasing and decreasing of antibonding interactions between central C4 ring and
      side donor groups cause destabilization of HOMO and stabilization of LUMO
      respectively in case of SQ compared to SMSQ molecules. This leads to decreasing
      the HOMO-LUMO gap and promotes biradicaloid character of SQ. The absorption
      maxima obtained by using TD-DFT method with BLYP, B3LYP, BHandHLYP, CAM-B3LYP and
      M06-2X functionals are not in good agreement with experimental results. On the
      other hand SAC-CI method gives better results for all the molecules. From this
      work we can evolve a design principle of these molecules which play a role as
      sensitizers in dye sensitized solar cells.

PMID- 22878862
TI  - Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of
      human carbonic anhydrase II.
AB  - We present molecular modeling of the structure and possible proton transfer
      pathways from the surface of the protein to the zinc-bound water molecule in the
      active site of the mutant His-107-Tyr of human carbonic anhydrase II (HCAII). No
      high-resolution structure or crystal structure is available till now for this
      particular mutant due to its lack of stability at physiological temperature. Our
      analysis utilizes as starting point a series of structures derived from high
      resolution crystal structure of the wild type protein. While many of the
      structures investigated do not reveal a complete path between the zinc bound
      water and His-64, several others do indicate the presence of a transient
      connection even when His-64 is present in its outward conformation. Mutation at
      the residue 107 also reveals the formation of a new path into the active site.
      Competing contributions from His-64 sidechain rotation from its outward
      conformation are also evaluated in terms of optimal path analysis. No indication
      of a lower catalytic efficiency of the mutant is evident from our results under
      the condition of thermal stability of the mutant.

PMID- 22878863
TI  - Dissipation of penconazole in tomatoes and soil.
AB  - Dissipation of penconazole was estimated in tomatoes fruits cultivated in field
      using QuEChERS method for sample preparation and high performance liquid
      chromatography with diode array detector. Following one application of normal
      dose 25 mL 100 L(-1) water, the average initial deposits of penconazole were
      observed to be 0.74 and 1.21 mg kg(-1) for tomatoes fruits and soil,
      respectively. The residues dissipated below the maximum residues limit of 0.2 mg
      kg(-1) after 15 days. The half-life value (T1/2) and preharvest interval of
      penconazole were 5.61 and 15 days, respectively. While (T1/2) of penconazole in
      soil was 15.51 days. Thus, a waiting period of 15 day was suggested for the safe
      consumption of penconazole treated Tomatoes.

PMID- 22878864
TI  - Pugilina morio L., a new imposex exhibitor from South American estuarine
      environments: approach for a non-lethal method to evaluate imposex.
AB  - This is the first report on imposex occurrence in Pugilina morio. Imposex levels
      in P. morio from Ceara River Estuary were assessed by a non-lethal method. The
      obtained imposex parameters were: percentage = 37.1 %, female penis length index
      (FPLI) = 0.93 mm, relative penis length index (RPLI) = 6.5 %, and vas deferens
      sequence index (VDSI) = 1.0. Because imposex is induced by tributyltin, and P.
      morio is widely distributed on the East coast of South America, the species can
      be used as a tributyltin contamination sentinel in these estuaries. Additionally,
      a non-lethal method of evaluating imposex minimized the impact on the population
      of P. morio from sample collection, as all organisms were returned to the
      environment.

PMID- 22878866
TI  - Optical trapping of microparticles using silicon nitride waveguide junctions and
      tapered-waveguide junctions on an optofluidic chip.
AB  - We study optical trapping of microparticles on an optofluidic chip using silicon
      nitride waveguide junctions and tapered-waveguide junctions. We demonstrate the
      trapping of single 1 MUm-sized polystyrene particles using the evanescent field
      of waveguide junctions connecting a submicrometer-sized input-waveguide and a
      micrometer-sized output-waveguide. Particle trapping is localized in the vicinity
      of the junction. We also demonstrate trapping of one and two 1MUm-sized
      polystyrene particles using tapered-waveguide junctions connecting a
      submicrometer-sized singlemode input-waveguide and a micrometer-sized multimode
      output-waveguide. Particle trapping occurs near the taper output end, the taper
      center and the taper input end, depending on the taper aspect ratio.

PMID- 22878865
TI  - Mechanisms of disease in frontotemporal lobar degeneration: gain of function
      versus loss of function effects.
AB  - Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and
      genetically heterogeneous. Three major proteins are implicated in its
      pathogenesis. About half of cases are characterized by depositions of the
      microtubule associated protein, tau (FTLD-tau). In most of the remaining cases,
      deposits of the transactive response (TAR) DNA-binding protein with Mw of 43 kDa,
      known as TDP-43 (FTLD-TDP), are seen. Lastly, about 5-10 % of cases are
      characterized by abnormal accumulations of a third protein, fused in sarcoma
      (FTLD-FUS). Depending on the protein concerned, the signature accumulations can
      take the form of inclusion bodies (neuronal cytoplasmic inclusions and neuronal
      intranuclear inclusions) or dystrophic neurites, in the cerebral cortex,
      hippocampus and subcortex. In some instances, glial cells are also affected by
      inclusion body formation. In motor neurone disease (MND), TDP-43 or FUS
      inclusions can present within motor neurons of the brain stem and spinal cord.
      This present paper attempts to critically examine the role of such proteins in
      the pathogenesis of FTLD and MND as to whether they might exert a direct
      pathogenetic effect (gain of function), or simply act as relatively innocent
      witnesses to a more fundamental loss of function effect. We conclude that
      although there is strong evidence for both gain and loss of function effects in
      respect of each of the proteins concerned, in reality, it is likely that each is
      a single face of either side of the coin, and that both will play separate,
      though complementary, roles in driving the damage which ultimately leads to the
      downfall of neurons and clinical expression of disease.

PMID- 22878867
TI  - Development of a single bovine embryo improved by co-culture with trophoblastic
      vesicles in vitamin-supplemented medium.
AB  - To improve the development of singly cultured bovine embryos, we developed a co
      culture method with trophoblastic vesicles. The growth of trophoblastic cells was
      markedly increased in vitamin-supplemented medium 199 compared with medium 199.
      Upon co-culture of a single embryo with trophoblastic vesicles in vitamin
      supplemented medium 199, embryo development to the blastocyst stage was
      significantly higher than in embryos co-cultured with trophoblastic vesicles in
      RPMI 1640 or with cumulus cells in medium 199 (control). In the absence of the
      vitamin cocktail, co-culture with trophoblastic vesicles in medium 199 did not
      improve embryo development compared with that of the control. The vitamin
      cocktail was effective in embryo development when co-cultured with trophoblastic
      vesicles, but not with cumulus cells. Embryo development was not improved in the
      absence of co-cultured trophoblastic vesicles, even in the presence of vitamin
      cocktail. In conclusion, the co-culture system with trophoblastic vesicles in
      vitamin-supplemented medium 199 efficiently enhances the development of singly
      cultured embryos.

PMID- 22878868
TI  - Nicotine treatment improves Toll-like receptor 2 and Toll-like receptor 9
      responsiveness in active pulmonary sarcoidosis.
AB  - BACKGROUND: New evidence links nicotine to the regulation of T cell-mediated
      inflammation via a 7 nicotinic cholinergic receptor activation, and chronic
      nicotine exposure (smoking) reduces the incidence of granulomatous diseases. We
      sought to determine whether nicotine treatment was well tolerated while
      effectively normalizing immune responses in patients with active pulmonary
      sarcoidosis. METHODS: Consenting adults with symptomatic sarcoidosis (n 5 13)
      were randomly assigned to receive 12 weeks of nicotine treatment plus
      conventional therapy or conventional therapy alone. Obtained blood cells were
      evaluated for their responsiveness to selected Toll-like receptor (TLR) and
      nucleotide oligomerization domain-like receptor ligands and T cell surface marker
      expression before and after nicotine treatment. Asymptomatic patients (n 5 6) and
      disease-free subjects (n 5 6) served as comparative control subjects. Adverse
      events were monitored for the duration of the study. RESULTS: Compared with the
      asymptomatic group, symptomatic patients had impaired peripheral responses to
      TLR2, TLR4, and TLR9 ligands (anergy) and reduced peripheral populations of CD4 1
      FoxP3 1 regulatory T cells (Tregs). Nicotine treatment was associated with
      restoration of TLR2 and TLR9 responsiveness, and expansion of Tregs, including
      the CD4 1 CD25 2 FoxP3 1 phenotype. There were no serious adverse events or signs
      of nicotine dependency. CONCLUSIONS: Nicotine treatment in active pulmonary
      sarcoidosis was well tolerated and restored peripheral immune responsiveness to
      TLR2 and TLR9 agonists and expansion of FoxP3 1 Tregs, including a specific
      "preactivated" (CD25 2 ) phenotype. The immune phenotype of patients with
      symptomatic sarcoidosis treated with nicotine closely resembled that of
      asymptomatic patients, supporting the notion that nicotine treatment may be
      beneficial in this patient population.

PMID- 22878869
TI  - Penehyclidine enhances the efficacy of tropisetron in prevention of PONV
      following gynecological laparoscopic surgery.
AB  - PURPOSE: Postoperative nausea and vomiting (PONV) are common complications after
      gynecological laparoscopic surgery. Because monotherapy with antiemetics is
      insufficient, combinations of various antiemetics are often recommended by
      experts. In this study, our purpose was to find out whether penehyclidine could
      enhance the efficacy of tropisetron in preventing PONV. METHODS: With hospital
      ethics committee approval, we investigated 120 women undergoing gynecological
      laparoscopic surgery receiving prophylactic tropisetron (0.1 mg/kg; maximal dose,
      5 mg) (group T) or tropisetron (0.1 mg/kg; maximal dose, 5 mg) plus penehyclidine
      (0.01 mg/kg; maximal dose, 1 mg) (group TP), or penehyclidine (0.01 mg/kg;
      maximal dose, 1 mg) (group P). The incidence of vomiting, the intensity of nausea
      (assessed by a visual analogue scale [VAS]), antiemetic rescues, and adverse
      effects were recorded at 2, 6, 12, and 24 h after surgery in the gynecological
      ward by a visiting nurse anesthetist who was unaware of the treatments. Collected
      data were analyzed using analysis of variance (ANOVA) and the chi(2) test.
      Continuous variables were expressed as means +/- SD, and non-continuous variables
      were expressed as n (%). RESULTS: The overall incidence of vomiting was 28.3 %
      (34/120) in our study. The incidence of vomiting was significantly lower in group
      TP (4 cases, 10 %) than that in group T (12 cases, 30 %) and group P (18 cases,
      45 %). The incidence of vomiting in group TP was also significantly lower than
      that in group T at 0-2 h and 2-6 h postoperatively and it was also significantly
      lower than that in group P at 0-2 h, 2-6 h, 6-12 h, and 12-24 h postoperatively.
      The incidence of vomiting was significantly lower in group T than that in group P
      at 12-24 h postoperatively. The VAS of nausea was significantly lower in group TP
      than that in group T and group P at 2 and 6 h after surgery. It also showed a
      significant higher score in group P than that at group T and group TP at 12 and
      24 h. Within group P, the VAS of nausea was significantly lower at 2 h
      postoperatively than that at 24 h. CONCLUSIONS: Penehyclidine showed less
      efficacy in preventing PONV than tropisetron; however, compared with tropisetron
      or penehyclidine monotherapy, prophylactic medication with tropisetron plus
      penehyclidine significantly reduced the incidence of vomiting and decreased the
      intensity of nausea in women undergoing gynecological laparoscopic surgery.

PMID- 22878870
TI  - CTA spot sign predicts hematoma expansion in patients with delayed presentation
      after intracerebral hemorrhage.
AB  - BACKGROUND: Hematoma expansion after acute intracerebral hemorrhage occurs most
      frequently in patients presenting within 3 h of symptom onset. However, the
      majority of patients present outside this window or with an unknown onset time.
      We investigated the prevalence of hematoma expansion in these patients and
      assessed the accuracy of the CT angiography (CTA) spot sign for identifying risk
      of hematoma expansion. METHODS: We analyzed 391 consecutive patients undergoing
      CTA and a followup CT. CTA spot sign readings were performed by two experienced
      readers and hematoma expansion was assessed by means of semi-automated software.
      RESULTS: Hematoma expansion occurred in 18 % of patients. When stratified by time
      from symptom onset to initial CT, hematoma expansion rates were: 39 % within 3 h;
      11 % between 3 and 6 h, 11 % beyond 6 h (but with known onset), and 20 % in
      patients with unknown symptom onset. Of patients who developed hematoma
      expansion, only 38 % presented within 3 h. The accuracy of the spot sign in
      predicting hematoma expansion was 0.67 for patients presenting within 3 h, 0.83
      between 3 and 6 h, 0.88 after 6 h, and 0.76 for patients presenting with an
      unknown onset time. CONCLUSIONS: A substantial number of patients destined to
      suffer from hematoma expansion present either late or with an unknown symptom
      onset time. The CTA spot sign accurately identifies patients destined to expand
      regardless of time from symptom onset, and may therefore open a path to offer
      clinical trials and novel therapies to the many patients who do not present
      acutely.

PMID- 22878871
TI  - Hospital admissions of adults with community-acquired pneumonia in Portugal
      between 2000 and 2009.
AB  - Recent studies in the USA and northern Europe have shown an increase in community
      acquired pneumonia (CAP). In southern Europe, this increase has not yet been
      documented. We carried out a retrospective analysis from encoded information from
      the Portuguese database for hospital admissions that included all individuals
      aged >=18 years, with a primary diagnosis of pneumonia, who were discharged
      between 2000 and 2009. We excluded patients infected with HIV, individuals
      immunocompromised as a result of anti-cancer or immunosuppressive treatment, and
      transplant recipients. Of the 294 027 admissions for CAP, 56% were male. The mean
      age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was
      a 5% increase in the average age of patients admitted with CAP. Admissions for
      CAP represented 3.7% of total admissions of adult patients. The average annual
      rate of hospital admissions for adults with CAP was 3.61 per 1000 total
      population, rising to 13.4 for those aged >=65 years. Between 2000-2004 and 2005
      2009 the average annual rate of hospital admission for CAP per 1000 population
      increased by 28.2%. Hospital admissions for CAP in Portugal increased between
      2000 and 2009. It has grown consistently over time, varying according to age with
      males over-represented.

PMID- 22878872
TI  - Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by
      caffeine.
AB  - In preterm human infants, briefly elevated concentrations of oxygen are
      associated with a prolonged increase in blood chemokine concentrations and the
      development of bronchopulmonary dysplasia (BPD). Caffeine given to preterm
      infants for the prevention or treatment of apnoea has been shown to reduce the
      rate of BPD. We tested the hypotheses that infant rats exposed to a combination
      of caffeine and hyperoxia would be less susceptible to lung injury than those
      exposed to hyperoxia alone and that caffeine decreases the pulmonary tissue
      expression of chemokines and leukocyte influx following hyperoxia. Using 6-day
      old rat pups, we demonstrated that 24 h of 80% oxygen exposure caused pulmonary
      recruitment of neutrophils and macrophages. High levels of oxygen upregulated the
      expression of: the CXC chemokines, cytokine-induced neutrophil chemoattractant-1
      and macrophage inflammatory protein-2; the CC-chemokine monocyte chemoattractant
      protein-1; the pro-inflammatory cytokines tumour necrosis factor-alpha and
      interleukin-6, as measured by realtime PCR after the administration of caffeine
      (10 mg . kg(-1) body weight); and attenuated chemokine and cytokine upregulation,
      as well as the influx of CD11b(+), ED-1(+) and myeloperoxidase(+) leukocytes.
      These experiments suggest that protective effects of caffeine in the neonatal
      lung are mediated, at least in part, by reduction of pulmonary inflammation.

PMID- 22878873
TI  - Effectiveness of sequential automatic-manual home respiratory polygraphy scoring.
AB  - Automatic home respiratory polygraphy (HRP) scoring functions can potentially
      confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating
      technician scoring) in a substantial number of patients. The result would have
      important management and cost implications. The aim of this study was to
      determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol
      (automatic and then manual for residual cases) compared with manual HRP scoring,
      and with in-hospital polysomnography. We included suspected SAHS patients in a
      multicentre study and assigned them to home and hospital protocols at random. We
      constructed receiver operating characteristic (ROC) curves for manual and
      automatic scoring. Diagnostic agreement for several cut-off points was explored
      and costs for two equally effective alternatives were calculated. Of 366
      randomised patients, 348 completed the protocol. Manual scoring produced better
      ROC curves than automatic scoring. There was no sensitive automatic or subsequent
      manual HRP apnoea-hypopnoea index (AHI) cut-off point. The specific cut-off
      points for automatic and subsequent manual HRP scorings (AHI >25 and >20,
      respectively) had a specificity of 93% for automatic and 94% for manual scorings.
      The costs of manual protocol were 9% higher than sequential HRP protocol; these
      were 69% and 64%, respectively, of the cost of the polysomnography. A sequential
      HRP scoring protocol is a cost-effective alternative to polysomnography, although
      with limited cost savings compared to HRP manual scoring.

PMID- 22878874
TI  - The impact of depressive symptoms on recovery and outcome of hospitalised COPD
      exacerbations.
AB  - The impact of depressive symptoms on outcomes of acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in
      prospective studies. We prospectively enrolled 230 consecutive patients
      hospitalised for AECOPD, without previous diagnosis of depression. Depressive
      symptoms were evaluated with Beck's depression inventory. Pulmonary function
      tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale
      were recorded on admission and on days 3, 10 and 40. Patients were evaluated
      monthly for 1 year. Patients with depressive symptoms required longer
      hospitalisation (mean +/- sd 11.6 +/- 3.7 versus 5.6 +/- 4.1 days, p<0.001).
      Clinical variables improved during the course of AECOPD, but depressive symptoms
      on admission had a significant impact on dyspnoea (p<0.001) and CAT score (p =
      0.012) improvement. Patients with depressive symptoms presented more AECOPD
      (p<0.001) and more hospitalisations for AECOPD (p<0.001) in 1 year. In
      multivariate analysis, depressive symptoms were an independent predictor of
      mortality (hazard ratio 3.568, 95% CI 1.302-9.780) and risk for AECOPD (incidence
      rate ratio (IRR) 2.221, 95% CI 1.573-3.135) and AECOPD hospitalisations (IRR
      3.589, 95% CI 2.319-5.556) in 1 year. The presence of depressive symptoms in
      patients admitted for AECOPD has a significant impact on recovery and is related
      to worse survival and increased risk for subsequent COPD exacerbations and
      hospitalisations in 1 year.

PMID- 22878875
TI  - Sweet talk: insights into the nature and importance of glucose transport in lung
      epithelium.
AB  - For over 50 years, glucose has been recognised to cross the lung epithelial
      barrier and be transported by lung epithelial cells. However, until recently,
      research into these processes focused on their effects on lung liquid volume.
      Here, we consider a newly identified role for pulmonary glucose transport in
      maintaining low airway surface liquid (ASL) glucose concentrations and propose
      that this contributes to lung defence against infection. Glucose diffuses into
      ASL via paracellular pathways at a rate determined by paracellular permeability
      and the transepithelial glucose gradient. Glucose is removed from ASL in proximal
      airways via facilitative glucose transporters, down a concentration gradient
      generated by intracellular glucose metabolism. In the distal lung, glucose
      transport via sodium-coupled glucose transporters predominates. These processes
      vary between species but universally maintain ASL glucose at 3-20-fold lower
      concentrations than plasma. ASL glucose concentrations are increased in
      respiratory disease and by hyperglycaemia. Elevated ASL glucose in intensive care
      patients was associated with increased Staphylococcus aureus infection. Diabetic
      patients with and without chronic lung disease are at increased risk of
      respiratory infection. Understanding of mechanisms underlying lung glucose
      homeostasis could identify new therapeutic targets for control of ASL glucose and
      prevention and treatment of lung infection.

PMID- 22878876
TI  - Airway epithelial cell apoptosis and inflammation in COPD, smokers and
      nonsmokers.
AB  - We hypothesised that primary bronchial epithelial cells (PBECs) from subjects
      with chronic obstructive pulmonary disease (COPD) respond differently to
      Pseudomonas aeruginosa lipopolysaccharide (LPS) after cigarette smoke extract
      (CSE) exposure than PBECs obtained from smokers without airflow obstruction and
      nonsmokers. PBECs from 16 COPD subjects, 10 smokers without airflow obstruction
      and nine nonsmokers were cultured at air-liquid interface. Cultures were
      incubated with CSE prior to stimulation with P. aeruginosa LPS. Interleukin (IL)
      6 and IL-8 were measured by ELISA and Toll-like receptor (TLR)-4 expression by
      fluorescence-activated cell sorter. Activation of nuclear factor (NF)-kappaB was
      determined by Western blotting and ELISA, and MAPK and caspase-3 activity by
      Western blotting. Apoptosis was evaluated using Annexin-V staining and the
      terminal transferase-mediated dUTP nick end-labelling methods. Constitutive
      release of IL-8 and IL-6 was greatest from the COPD cultures. However, CSE
      pretreatment followed by P. aeruginosa LPS stimulation reduced IL-8 release from
      COPD PBECs, but increased it from cells of smokers without airflow obstruction
      and nonsmokers. TLR-4 expression, MAPK and NF-kappaB activation in COPD cultures
      were reduced after CSE treatment, but not in the smokers without airflow
      obstruction or nonsmoker groups, which was associated with increased apoptosis.
      CSE attenuates inflammatory responses to LPS in cells from people with COPD but
      not those from nonsmoking individuals and those who smoke without airflow
      obstruction.

PMID- 22878877
TI  - Shared Pseudomonas aeruginosa genotypes are common in Australian cystic fibrosis
      centres.
AB  - Recent molecular-typing studies suggest cross-infection as one of the potential
      acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis
      (CF). In Australia, there is only limited evidence of unrelated patients sharing
      indistinguishable P. aeruginosa strains. We therefore examined the point
      prevalence, distribution, diversity and clinical impact of P. aeruginosa strains
      in Australian CF patients nationally. 983 patients attending 18 Australian CF
      centres provided 2887 sputum P. aeruginosa isolates for genotyping by
      enterobacterial repetitive intergenic consensus-PCR assays with confirmation by
      multilocus sequence typing. Demographic and clinical details were recorded for
      each participant. Overall, 610 (62%) patients harboured at least one of 38 shared
      genotypes. Most shared strains were in small patient clusters from a limited
      number of centres. However, the two predominant genotypes, AUST-01 and AUST-02,
      were widely dispersed, being detected in 220 (22%) and 173 (18%) patients
      attending 17 and 16 centres, respectively. AUST-01 was associated with
      significantly greater treatment requirements than unique P. aeruginosa strains.
      Multiple clusters of shared P. aeruginosa strains are common in Australian CF
      centres. At least one of the predominant and widespread genotypes is associated
      with increased healthcare utilisation. Longitudinal studies are now needed to
      determine the infection control implications of these findings.

PMID- 22878878
TI  - Transmission of multidrug-resistant and extensively drug-resistant tuberculosis
      in a metropolitan city.
AB  - Multidrug-resistant (MDR)- tuberculosis (TB) and extensively drug resistant (XDR)
      TB reportedly lead to increased household transmission. This is a retrospective
      cohort study of active TB occurring among household contacts exposed to MDR-TB.
      Of 704 contacts in 246 households, initial screening identified 12 (1.7%) TB
      cases (prevalent cases) and 17 (2.4%) contacts that subsequently developed active
      TB (secondary cases) after a median (range) duration of 17 (5-62.5) months. Eight
      prevalent cases and three secondary cases had MDR-TB. TB incidence rates per
      100,000 person-years were 254.9 overall and 45.0 for MDR-TB. XDR-TB in the index
      MDR-TB patient significantly increased the odds of identifying a prevalent TB
      case to 4.8 (95% CI 1.02-22.5), and the hazard of finding a secondary TB case to
      4.7 (95% CI 1.7-13.5). Molecular fingerprinting confirmed household transmission
      of MDR-TB. Of 20 retrievable isolates from 27 XDR-TB index cases, restriction
      fragment length polymorphism analysis showed clustering among 13 (65%), with 11
      (55%) due to recent transmission by n-1 method and an identifiable household
      source in only three (27.2%) of the 11 cases. XDR-TB relative to MDR-TB
      significantly increases household transmission of TB, probably reflecting
      prolonged/higher infectivity, and indicating a need for prolonged household
      surveillance. XDR-TB may largely transmit outside of the household settings.

PMID- 22878879
TI  - Short-form Sun-style t'ai chi as an exercise training modality in people with
      COPD.
AB  - The aims of the study were to determine the effect of short-form Sun-style t'ai
      chi (SSTC) (part A) and investigate exercise intensity of SSTC (part B) in people
      with chronic obstructive pulmonary disease (COPD). Part A: after confirmation of
      eligibility, participants were randomly allocated to either the t'ai chi group or
      control group (usual medical care). Participants in the t'ai chi group trained
      twice weekly for 12 weeks. Part B: participants who had completed training in the
      t'ai chi group performed a peak exercise test (incremental shuttle walk test) and
      SSTC while oxygen consumption (VO2) was measured. Exercise intensity of SSTC was
      determined by the per cent of VO2 reserve. Of 42 participants (mean +/- sd forced
      expiratory volume in 1 s 59 +/- 16% predicted), 38 completed part A and 15
      completed part B. Compared to control, SSTC significantly increased endurance
      shuttle walk time (mean difference 384 s, 95% CI 186-510); reduced medial-lateral
      body sway in semi-tandem stand (mean difference -12.4 mm, 95% CI -21- -3); and
      increased total score on the chronic respiratory disease questionnaire (mean
      difference 11 points, 95% CI 4-18). The exercise intensity of SSTC was 53 +/- 18%
      of VO2 reserve. SSTC was an effective training modality in people with COPD
      achieving a moderate exercise intensity which meets the training recommendations.

PMID- 22878880
TI  - Evaluation of QuantiFERON microtube, using 0.9 mL blood, for diagnosing
      tuberculosis infection.
AB  - The performance of QuantiFERON microtube (QFT-MT), using 0.9 mL blood, and
      QuantiFERON-TB Gold in-tube test (QFT-IT) (3 mL blood), for diagnosing
      tuberculosis (TB) was compared in children and adults in an endemic setting. In
      152 children with suspected TB and 87 adults with confirmed TB, QFT-IT was
      compared with two QFT-MT concentrations (QFT-MT A and B). Proportions of positive
      and indeterminate results, interferon (IFN)-gamma responses, interassay agreement
      and sensitivity were assessed. We found similar proportions of indeterminate
      results, levels of IFN-gamma and comparable sensitivity. The interassay agreement
      was moderate in all children (QFT-IT versus QFT-MT A: 85%, k=0.44 and QFT-IT
      versus QFT-MT B: 88%, k=0.50) and adults (QFT-IT versus QFT-MT A: 88%, k=0.50 and
      QFT-IT versus QFT-MT B: 89%, k=0.49). Sensitivity was low (QFT-IT 23%, QFT-MT A
      18% and B 19%) in children with confirmed or highly probable TB compared with
      adults (83%, 86% and 88%, respectively). The QFT-MT test can be reliably
      performed using less than one-third of the blood volume used in QFT-IT. The
      reduced volume may be useful for research and future diagnosis of paediatric TB.
      The poor sensitivity and high indeterminate rate of both IFN-gamma release assays
      in severely ill children, with immature or impaired immunity in an endemic
      setting, warrants further investigations.

PMID- 22878881
TI  - Defining race/ethnicity and explaining difference in research studies on lung
      function.
AB  - The 2005 guidelines of the American Thoracic Society/European Respiratory Society
      recommend the use of race- and/or ethnic-specific reference standards for
      spirometry. Yet definitions of the key variables of race and ethnicity vary
      worldwide. The purpose of this study was to determine whether researchers defined
      race and/or ethnicity in studies of lung function and how they explained any
      observed differences. Using the methodology of the systematic review, we searched
      PubMed in July 2008 and screened 10 471 titles and abstracts to identify
      potentially eligible articles that compared "white" to "other racial and ethnic
      groups". Of the 226 eligible articles published between 1922 and 2008, race
      and/or ethnicity was defined in 17.3%, with the proportion increasing to 70% in
      the 2000s for those using parallel controls. Most articles (83.6%) reported that
      "other racial and ethnic groups" have a lower lung capacity compared to "white";
      94% of articles failed to examine socioeconomic status. In the 189 studies that
      reported lower lung function in "other racial and ethnic groups", 21.8% and 29.4%
      of explanations cited inherent factors and anthropometric differences,
      respectively, whereas 23.1% of explanations cited environmental and social
      factors. Even though researchers sought to determine differences in lung function
      by race/ethnicity, they typically failed to define their terms and frequently
      assumed inherent (or genetic) differences.

PMID- 22878882
TI  - Extracorporeal membrane oxygenation in a nonintubated patient with acute
      respiratory distress syndrome.

PMID- 22878883
TI  - CFTR biomarkers: time for promotion to surrogate end-point.
AB  - In patients with cystic fibrosis, cystic fibrosis transmembrane conductance
      regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal
      potential difference, are used as end-points of efficacy in phase-III clinical
      trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren.
      The aim of this project was to review the literature on reliability, validity and
      responsiveness of nasal potential difference, sweat chloride and intestinal
      current measurement in patients with cystic fibrosis. Data on clinimetric
      properties were collected for each biomarker and reviewed by an international
      team of experts. Data on reliability, validity and responsiveness were tabulated.
      In addition, narrative answers to four key questions were discussed and agreed by
      the team of experts. The data collected demonstrated the reliability, validity
      and responsiveness of nasal potential difference. Fewer data were found on
      reliability of sweat chloride concentration; however, validity and responsiveness
      were demonstrated. Validity was demonstrated for intestinal current measurement,
      but further information is required on reliability and responsiveness. For all
      three end-points, normal values were collected and further research requirements
      were proposed. This body of work adds useful information to support the promotion
      of CFTR biomarkers to surrogate end-points and to guide further research in the
      area.

PMID- 22878884
TI  - Regional lung function and heterogeneity of specific gas volume in healthy and
      emphysematous subjects.
AB  - The aim of our study was to study regional lung function by standard computed
      tomography (CT) and characterise regional variations of density and specific gas
      volume (SVg) between different lung volumes. We studied 10 healthy and 10
      severely emphysematous subjects. Corresponding CT images taken at high and low
      lung volumes were registered by optical flow to obtain two-dimensional maps of
      pixel-by-pixel differences of density (DeltaHU) and SVg (DeltaSVg) at slice
      levels near the aortic arch, carina and top diaphragm. In healthy subjects,
      DeltaHU was higher at all levels (p<0.001) with higher variability expressed as
      interquartile range (p<0.001), largely due to its differences between dorsal and
      ventral regions. In patients, median DeltaSVg values were 3.2 times lower than
      healthy volunteers (p<0.001), while heterogeneity of DeltaSVg maps, expressed as
      quartile coefficient of variation, was 5.4 times higher (p<0.001). In all
      patients, there were areas with negative values of DeltaSVg. In conclusion,
      DeltaSVg is uniform in healthy lungs and minimally influenced by gravity. The
      significant DeltaSVg heterogeneity observed in emphysema allows identification of
      areas of alveolar destruction and gas trapping and suggests that DeltaSVg maps
      provide useful information for evaluation and planning of emerging treatments
      that target trapped gas for removal.

PMID- 22878885
TI  - The influence of temperature on C153 steady-state absorption and fluorescence
      kinetics in hydrogen bonding solvents.
AB  - In a recent paper (J Fluoresc (2011) 21:1547-1557) a temperature induced
      modulation of Coumarin 153 (C153) fluorescence lifetime and quantum yield for the
      probe dissolved in the polar, nonspecifically interacting 1-chloropropane was
      reported. This modulation was also observed in temperature dependencies of the
      radiative and nonradiative rates. Here, we show that the modulation is also
      observed in another 1-chloroalkane-1-chlorohexane, as well as in hydrogen bonding
      propionitrile, ethanol and trifluoroethanol. Change in the equilibrium distance
      between S (0) an S (1) potential energies surfaces was identified as the source
      of this modulation. This change is driven by temperature changes. It leads to a
      modulation of the fluorescence transition dipole moment and it is the primary
      source of the experimental effects observed. Additionally, we have found that
      proticity of the solvent induces a rise in the fluorescence transition dipole
      moment, which leads to a shortening of the fluorescence lifetime. Hydrogen bonds
      are formed by C153 also with hydrogen accepting solvents like propionitrile. We
      show that while such bonds do not affect the transition probability, they do
      change the S(0) an S(1) energy gap which in turn implies a change in non
      radiative transition rate in a similar way as in protic solvents, as well as in
      the fluorescence spectrum position. Finally, the influence of temperature on the
      energies of hydrogen bonds formed by C153 when acting as hydrogen donor or
      acceptor is reported.

PMID- 22878887
TI  - Colorectal cancer in inflammatory bowel diseases: CT features with pathological
      correlation.
AB  - PURPOSE: To describe CT features of inflammatory bowel disease (IBD)-related
      colorectal cancer and correlate the imaging findings with histopathological
      findings. MATERIALS AND METHODS: CT imaging findings in 17 patients with IBD
      related colorectal cancer were retrospectively evaluated. Imaging findings were
      correlated with surgical and histopathological findings. Univariate and
      multivariate analyses explored the relationships between CT and histopathological
      variables. RESULTS: Two different CT patterns were individualized including
      clearly visible soft tissue mass (8/17; 47%) (Type 1 tumor) or stenosis with
      marked circumferential thickening resembling inflammation (9/17; 53%) (Type 2
      tumor). At univariate analysis, thickness of tumor-free colorectal wall at CT was
      greater in Crohn disease (median, 13 mm) than in ulcerative colitis (median, 7
      mm) (P = 0.011). Significant association was found between presence of signet
      ring cells and Type 2 tumor at CT (6/9, 67% P = 0.009) and colonic dilatation
      proximal to tumor (5/6, 83%; P = 0.035). At multivariate analysis, free-fluid
      effusion was the single independent CT variable predictive for the presence of
      signet ring cells (odds ratio = 50; 95% CI 2.56-977.02; P = 0.01). CONCLUSION:
      Colorectal cancer in IBD displays two main features on CT. Type 2 tumors and free
      fluid effusion correlate with presence of signet ring cells. Knowledge of these
      findings is critical to help suggest the diagnosis.

PMID- 22878886
TI  - Association between longer therapy with thiazolidinediones and risk of bladder
      cancer: a cohort study.
AB  - BACKGROUND: The use of pioglitazone, a thiazolidinedione (TZD), may increase the
      risk of bladder cancer in patients with type 2 diabetes. In this study, we
      assessed the risk of bladder cancer associated with the use of TZDs and between
      pioglitazone and rosiglitazone, an alternative TZD. METHODS: We conducted a
      retrospective cohort study of patients with type 2 diabetes mellitus who
      initiated treatment with a TZD (n = 18 459 patients) or a sulfonylurea (SU) (n =
      41 396 patients) between July 1, 2000, and August 31, 2010, using The Health
      Improvement Network database in the United Kingdom. Incident cancers were
      identified for 196 708 person-years of follow-up. Cox proportional hazards
      regression models were used to estimate hazard ratios (HRs) and 95% confidence
      intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU
      cohort (referent), adjusted for potential confounders. Risk associated with
      increasing duration of drug exposure was also examined. All statistical tests
      were two-sided. RESULTS: We identified 60 incident bladder cancers in the TZD
      cohort and 137 cancers in the SU cohort. No difference in bladder cancer risk was
      found between the two cohorts (TZD vs SU, HR = 0.93, 95% CI = 0.68 to 1.29) in
      analyses that did not account for duration of exposure. However, the risk of
      bladder cancer was increased among patients with the longest duration of TZD vs
      SU therapy (>= 5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those
      with the longest time since initiation of therapy (>= 5 years since first use, HR
      = 2.53, 95% CI = 1.12 to 5.77). Risk of bladder cancer also increased with
      increasing time since initiation of pioglitazone (P (trend) < .001) and
      rosiglitazone (P (trend) = .006). Comparison of pioglitazone to rosiglitazone use
      did not demonstrate difference in cancer risk (P = .49). CONCLUSION: Long-term
      TZD therapy (>= 5 years) in patients with type 2 diabetes may be associated with
      an increased risk of bladder cancer, which may be common to all TZDs.

PMID- 22878888
TI  - Prevalence of cryptosporidiosis in dairy cattle, cattle-keeping families, their
      non-cattle-keeping neighbours and HIV-positive individuals in Dagoretti Division,
      Nairobi, Kenya.
AB  - This paper reports a study estimating the prevalence of cryptosporidiosis, an
      emerging zoonosis, in people and cattle in Dagoretti, Nairobi. A repeated cross
      sectional survey was carried out among randomly selected cattle keepers in
      Dagoretti, their dairy cattle and their non-cattle-keeping neighbours in the dry
      and wet seasons of 2006. A survey was also carried out among a group of people
      living with human immunodeficiency virus (HIV). Faecal samples were examined for
      Cryptosporidium oocysts using the modified Ziehl-Neelsen method; 16 % of the
      samples were also examined using immunofluorescence antibody (IFA) technique.
      Quality control consisted of blind reviews of slides, examining split samples and
      confirming slide results with IFA. We found that members of dairy households had
      a dry season cryptosporidiosis prevalence of 4 % and wet season prevalence of 0.3
      %, and non-dairy households, a prevalence of 5 and 0 %, respectively. The cattle
      dry season prevalence was 15 %, and the wet season prevalence, 11 %. The
      prevalence in people living with HIV was 5 %. The laboratory quality control
      system showed some inconsistency within and between different tests, indicating
      challenges in obtaining consistent results under difficult field and working
      conditions. In conclusion, this is the first reported study to simultaneously
      survey livestock, livestock keepers and their neighbours for cryptosporidiosis.
      We failed to find evidence that zoonotic cryptosporidiosis is important overall
      in this community. This study also draws attention to the importance of quality
      control and its reporting in surveys in developing countries.

PMID- 22878889
TI  - The importance of HER2 signaling in the tumor-initiating cell population in
      aromatase inhibitor-resistant breast cancer.
AB  - Aromatase inhibitors (AIs) are an effective therapy in treating estrogen receptor
      positive breast cancer. Nonetheless, a significant percentage of patients either
      do not respond or become resistant to AIs. Decreased dependence on ER-signaling
      and increased dependence on growth factor receptor signaling pathways,
      particularly human epidermal growth factor receptor 2 (EGFR2/HER2), have been
      implicated in AI resistance. However, the role of growth factor signaling remains
      unclear. This current study investigates the possibility that signaling either
      through HER2 alone or through interplay between epidermal growth factor receptor
      1 (EGFR/HER1) and HER2 mediates AI resistance by increasing the tumor initiating
      cell (TIC) subpopulation in AI-resistant cells via regulation of stem cell
      markers, such as breast cancer resistance protein (BCRP). TICs and BCRP are both
      known to be involved in drug resistance. Results from in vitro analyses of AI
      resistant versus AI-sensitive cells and HER2-versus HER2+ cells, as well as from
      in vivo xenograft tumors, indicate that (1) AI-resistant cells overexpress both
      HER2 and BCRP and exhibit increased TIC characteristics compared to AI-sensitive
      cells; (2) inhibition of HER2 and/or BCRP decrease TIC characteristics in
      letrozole-resistant cells; and (3) HER2 and its dimerization partner EGFR/HER1
      are involved in the regulation of BCRP. Overall, these results suggest that
      reducing or eliminating the TIC subpopulation with agents that target BCRP, HER2,
      EGFR/HER1, and/or their downstream kinase pathways could be effective in
      preventing and/or treating acquired AI resistance.

PMID- 22878890
TI  - MMP-9 increases HER2/neu expression and alters apoptosis levels in human mammary
      epithelial cells (HMEC).
AB  - HER2/neu overexpression leads to poorer prognosis and higher risk of disease
      reoccurrence in breast cancer patients. The causative factors responsible for
      increasing HER2/neu expression levels on mammary cells are not known. We
      investigated whether factors associated with inflammation or metastasis could
      induce HER2/neu expression on human mammary epithelial cells (HMECs). Human
      mammary epithelial cells and several human breast cancer cell lines used in our
      studies were treated with several agents, including estrogen and matrix
      metalloproteinase-9 (MMP-9), either alone or in various combinations. Relative
      expression of HER2/neu on the surface of target cells was assessed using
      fluorochrome-tagged antibodies and a fluorescence cytometer. HER2/neu gene
      expression was also determined by Western blot analysis and PCR. Apoptosis levels
      were also determined. MMP-9, administered either alone or in combination with
      interleukin-7 and estrogen, caused a significant rise in HER2/neu expression on
      the surface of HMECs. The induction in HER2/neu protein expression was suppressed
      using a MMP-9 inhibitor. Similar results were obtained for breast cancer cells
      treated with the estrogen in combination with MMP-9. MMP-9 treatment
      significantly decreased apoptotic levels in HMECs. Our results indicate that MMP
      9 is a regulator of HER2/neu expression on human mammary epithelial cells and
      suggest that upregulation of HER2/neu by MMP-9 may be relevant to altering the
      characteristics of normal mammary cells toward a transformed phenotype.

PMID- 22878891
TI  - Rhythmic oscillation of histone acetylation and methylation at the Arabidopsis
      central clock loci.
AB  - Circadian clock genes are regulated by a transcriptional-translational feedback
      loop. In Arabidopsis, LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK
      ASSOCIATED 1 (CCA1) transcripts are highly expressed in the morning. Translated
      LHY and CCA1 proteins repress the expression of TIMING OF CAB EXPRESSION 1
      (TOC1), which peaks in the evening. TOC1 protein induces expression of LHY and
      CCA1, forming a negative feedback loop which is believed to constitute the
      oscillatory mechanism of the clock. The rhythmic oscillation of mouse clock genes
      mPERIOD 1 (mPER1) and mPER2 has been correlated with regular alteration of
      chromatin structure through histone acetylation/deacetylation. However, little is
      known about the relationship between the transcriptional activity of Arabidopsis
      clock genes and their chromatin status. Here, we report that histone H3
      acetylation (H3Ac) and H3 lysine 4 tri-methylation (H3K4me3) levels at LHY, CCA1,
      and TOC1 are positively correlated with the rhythmic transcript levels of these
      genes, whereas H3K36me2 level shows a negative correlation. Thus, our study
      suggests rhythmic transcription of Arabidopsis clock genes might be regulated by
      rhythmic histone modification, and it provides a platform for future
      identification of clock-controlling histone modifiers.

PMID- 22878892
TI  - Identification and validation of potential conserved microRNAs and their targets
      in peach (Prunus persica).
AB  - MicroRNAs are a class of small, endogenous, non-coding RNA molecules that
      negatively regulate gene expression at the transcriptional or the post
      transcriptional level. Although a large number of miRNAs have been identified in
      many plant species, especially from model plants and crops, they remain largely
      unknown in peach. In this study, 110 potential miRNAs belonging to 37 families
      were identified using computational methods. A total of 43 potential targets were
      found for 21 families based on near-perfect or perfect complementarity between
      the plant miRNA and the target sequences. A majority of the targets were
      transcription factors which play important roles in peach development. qRT-PCR
      analysis of RNA samples prepared from different peach tissues for 25 miRNA
      families revealed that miRNAs were differentially expressed in different tissues.
      Furthermore, two target genes were experimentally verified by detection of the
      miRNA-mediated mRNA cleavage sites in peach using RNA ligase-mediated 5' rapid
      amplification of cDNA ends (RLM-RACE). Finally, we studied the expression pattern
      of the two target genes in three different tissues of peach to further understand
      the mechanism of the interaction between miRNAs and their target genes.

PMID- 22878893
TI  - [Scope and limitations of the median nerve mouse model in research on peripheral
      nerve regeneration].
AB  - INTRODUCTION: Peripheral nerve regeneration is usually studied in rat animal
      models (N. medianus or N. ischiadicus). In this article, we further evaluate the
      mouse median nerve model with its advantages and possible pitfalls. MATERIALS AND
      METHODS: 24 mice (C57BL/6) were operated. The median nerve was exposed in the
      left axilla. After transection, immediate microsurgical repair followed using
      11/0 sutures. In the contralateral axilla, 1 cm of median nerve was resected.
      After the operation, functional regeneration of the median nerve was assessed
      using the grasping test. Histological analysis was performed after staining with
      toluidine blue. RESULTS: All animals survived the procedure. Grip strength
      increased starting at day 10 and reached its maximum at day 35. Myelinated fibres
      in the regenerated nerves showed a smaller diameter and a thinner myelin sheath
      and the typical microfasciculation of regenerated nerve fibres in comparison to
      the uninjured nerve. CONCLUSION: The mouse median nerve model is technically
      demanding but opens a wide field of possible research options using genetically
      modified mice.

PMID- 22878895
TI  - Genetic polymorphisms and traumatic brain injury: the contribution of individual
      differences to recovery.
AB  - Recovery after Traumatic Brain Injury (TBI) is variable, even for patients with
      similar severity of brain injury. Recent research has highlighted the
      contribution that genetic predisposition plays in determining TBI outcome. This
      review considers the potential for genetic polymorphisms to influence recovery of
      cognitive and social processes following TBI. Limitations and considerations that
      researchers should make when assessing the potential impact of polymorphisms on
      TBI outcome are also discussed. Understanding the genetic factors that support
      neuroplasticity will contribute to an understanding of the variation in outcome
      following injury and help to identify potential targets for rehabilitation. 

PMID- 22878896
TI  - Anatomical reconstruction of the medial patellofemoral ligament in children with
      open growth-plates.
AB  - Recurrent lateral patellar dislocation is a common knee injury in the skeletally
      immature adolescent. In adults, anatomical reconstruction of the medial
      patellofemoral ligament (MPFL) is recommended, but due to the open physis,
      operative therapy in children is more challenging. We present a minimal invasive
      technique for anatomical reconstruction of the MPFL in children respecting the
      distal femoral physis. This technical note considers the important fact that the
      femoral insertion is distal to the femoral physis. Since the importance of an
      anatomical reconstruction respecting the femoral insertion of the ligament has
      been proven an insertion proximal of the physis has to be strictly avoided.

PMID- 22878897
TI  - Perception by family members and ICU staff of the quality of dying and death in
      the ICU: a prospective multicenter study in The Netherlands.
AB  - OBJECTIVE: Admission to the ICU is a major event in a patient's life and also for
      family members. We tried to elucidate how family members and ICU caregivers
      experience the dying process of their patients. METHODS: The prospective study
      took place in three Dutch ICUs. Patients who had stayed . 48 h and died in the
      ICU were eligible. The Quality of Dying and Death (QODD) questionnaire was used,
      with addition of items pertaining to the patient's autonomy. Values indicate
      median and interquartile range. RESULTS: We included 100 consecutive patients.
      ICU stay before death was 8 (3-16) days. APACHE (Acute Physiology and Chronic
      Health Evaluation) II score at admission was 24 (19-31). Family response rate was
      89%. Families were satisfied with overall QODD (score, 8 [7-9]) and felt
      supported by the ICU caregivers (8 [7-9]). Pain control was scored lower by
      family members (8 [5.75- 8.25]) than by nurses and physicians (9 [8-10], P 5
      .024) Almost always, physicians discussed the patient's end-of-life wishes with
      family members, although families rated the quality of the discussion lower (7
      [5.5-8.5]) than physicians (9 [6.5-10]) ( P 5 .045). The majority of the families
      (89%) felt included in the decision-making process. More than one-half of the
      family members (57%) believed that the physician made the fi nal decision alone
      after giving information, whereas 36.8% believed they had participated in making
      the decision. Family members rated the QODD questionnaire as difficult (6 [5-8]),
      and several items were not answered by a majority of family members. CONCLUSIONS:
      Quality of dying and death is generally perceived to be good by family members
      and caregivers of patients who die in Dutch ICUs. There is a need for
      modification of the QODD questionnaire for the European ICU population.

PMID- 22878898
TI  - Dietary lifestyle and colorectal cancer onset, recurrence, and survival: myth or
      reality?
AB  - BACKGROUND AND PURPOSE: Interest in the possibility that diet might help to
      reduce the risk of colorectal cancer dates back to 1970 based on both the large
      variation in rates of specific cancers in different countries and the impressive
      changes observed in the incidence of cancer in migrants from low- to high-risk
      areas. Here, we report the state of art of literature data about this topic.
      METHODS: Three sections have been separately considered: chemoprevention of first
      tumor onset, chemoprevention of recurrence after surgery, and chemoprevention of
      polyp recurrence in the course of the follow-up of subjects with elevated risk. A
      particular attention has been pointed to dietary factors and survival, whose
      relevance is showing a growing interest. RESULTS: The relationship between diet
      and colorectal cancer has been extensively studied about the onset, sometimes
      with controversial results. Its influence on recurrence and survival has been
      examined in only few studies. CONCLUSIONS: Literature data are convincing for a
      protective role on the onset of preneoplastic and neoplastic lesions for some
      foods such as fibers, vitamin A and D, folic acid, calcium, antioxidants, and
      promising perspectives for some substances such as phyto-estrogens. Less evidence
      based data are available on the possibility to avoid the recurrence of the
      disease or to affect its mortality with dietary habits. Future perspectives will
      be directed be not only to identify new dietary style able to prevent the onset
      of neoplastic lesion of the colon but also to realize an effective
      chemoprevention.

PMID- 22878899
TI  - T cell profiling reveals high CD4+CTLA-4 + T cell frequency as dominant predictor
      for survival after prostate GVAX/ipilimumab treatment.
AB  - Immune checkpoint blockade enhances antitumor responses, but can also lead to
      severe immune-related adverse events (IRAE). To avoid unnecessary exposure to
      these potentially hazardous agents, it is important to identify biomarkers that
      correlate with clinical activity and can be used to select patients that will
      benefit from immune checkpoint blockade. To understand the consequences of CTLA-4
      blockade and identify biomarkers for clinical efficacy and/or survival, an
      exploratory T cell monitoring study was performed in a phase I/II dose
      escalation/expansion trial (n = 28) of combined Prostate GVAX/ipilimumab
      immunotherapy. Phenotypic T cell monitoring in peripheral blood before and after
      Prostate GVAX/ipilimumab treatment revealed striking differences between patients
      who benefited from therapy and patients that did not. Treatment-induced rises in
      absolute lymphocyte counts, CD4(+) T cell differentiation, and CD4(+) and CD8(+)
      T cell activation were all associated with clinical benefit. Moreover,
      significantly prolonged overall survival (OS) was observed for patients with high
      pre-treatment frequencies of CD4(+)CTLA-4(+), CD4(+)PD-1(+), or differentiated
      (i.e., non-naive) CD8(+) T cells or low pre-treatment frequencies of
      differentiated CD4(+) or regulatory T cells. Unsupervised clustering of these
      immune biomarkers revealed cancer-related expression of CTLA-4(+) in CD4(+) T
      cells to be a dominant predictor for survival after Prostate GVAX/ipilimumab
      therapy and to thus provide a putative and much-needed biomarker for patient
      selection prior to therapeutic CTLA4 blockade.

PMID- 22878900
TI  - Safe communities in China as a strategy for injury prevention and safety
      promotion programmes in the era of rapid economic growth.
AB  - Due to its rapid economic development, China is facing a huge health, social, and
      economic burden resulting from injuries. The study's objective was to examine
      Safe Communities in China as a strategy for injury prevention and safety
      promotion programmes in the era of rapid economic growth. Literature searches in
      English and Chinese, which included grey literature, were performed on the
      Chinese Journal Full-text Search System and Medline, using the words "Safe
      Community", "injury", "economics", and "prevention". The results showed that the
      existing 35 recognized members of the International Safe Community Network have
      not placed due emphasis on suicide prevention, which is one of the leading
      problems in both rural and urban China. A few groups, such as children, the
      elderly, cyclists, and pedestrians, have received due emphasis, while other
      vulnerable groups, such as migrant workers, motorcyclists, students, players, and
      farmers have not received the necessary attention from the Safe Community
      perspective. As the evidence describes, Safe Communities in China can be a very
      effective strategy for injury prevention, but four aspects need to be
      strengthened in the future: (1) establish and strengthen the policy and
      regulations in terms of injury prevention at the national level; (2) create a
      system to involve professional organizations and personnel in projects; (3)
      consider the economic development status of different parts of China; and (4)
      intentional injury prevention should receive greater attention.

PMID- 22878901
TI  - The population and high-risk approaches to prevention: quantitative estimates of
      their contribution to population health in the Netherlands, 1970-2010.
AB  - BACKGROUND: To compare the contribution of 'population' and 'high-risk'
      approaches to prevention, with regard to their impact on population health in the
      Netherlands between 1970 and 2010. METHODS: Preventive interventions that have
      had an impact on mortality and morbidity rates were identified using published
      evaluation studies and routinely collected mortality and morbidity data. These
      interventions were then classified into population versus high-risk approaches,
      depending on whether they were targeted to groups identified on the basis of
      their risk of disease. RESULTS: In the period 1970-2010, 22 new preventive
      interventions were introduced, which altogether avoided about 16 000 deaths and
      several hundred thousand disease cases per year in the Netherlands. Tobacco
      control and road safety measures had the largest impact. Preventive interventions
      based on a high-risk approach, such as hypertension detection and control and
      cancer screening, accounted for approximately one quarter of the total health
      gain. CONCLUSIONS: In the period 1970-2010, considerably larger health gains have
      been achieved with the population approach than with the high-risk approach to
      prevention. National prevention policies should make judicious use of these
      complementary approaches to maximize health gain.

PMID- 22878902
TI  - Fetal growth and body size genes and risk of childhood acute lymphoblastic
      leukemia.
AB  - Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL)
      may be initiated in utero or early in the postnatal period. High birth weight (or
      rapid fetal growth) is associated with risk of ALL, but the mechanisms are not
      understood. In a population-based epidemiologic study of childhood ALL, we
      utilized a haplotype-based approach to assess the role of eight genes involved in
      fetal growth and body size regulation in 377 childhood ALL cases and 448
      controls. We found significant haplotype associations with risk of childhood ALL
      for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among
      Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051
      and 0.009, respectively). No haplotype associations were observed for IGF1R or
      the studied genes involved in body size regulation, including LEP, LEPR, GHRL,
      and NPY. Our study is the first to identify an association between the genes
      involved in the IGF axis and risk of childhood ALL. These findings for childhood
      ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are
      not yet fully differentiated and therefore more susceptible to malignant
      transformation. Additional studies are needed to confirm these findings and
      identify specific causal variants.

PMID- 22878903
TI  - Influence of choice of yeasts on volatile fermentation-derived compounds, colour
      and phenolics composition in Cabernet Sauvignon wine.
AB  - Wine colour, phenolics and volatile fermentation-derived composition are the
      quintessential elements of a red wine. Many viticultural and winemaking factors
      contribute to wine aroma and colour with choice of yeast strain being a crucial
      factor. Besides the traditional Saccharomyces species S. cerevisiae, S. bayanus
      and several Saccharomyces interspecific hybrids are able to ferment grape juice
      to completion. This study examined the diversity in chemical composition,
      including phenolics and fermentation-derived volatile compounds, of an Australian
      Cabernet Sauvignon due to the use of different Saccharomyces strains. Eleven
      commercially available Saccharomyces strains were used in this study; S.
      cerevisiae (7), S. bayanus (2) and interspecific Saccharomyces hybrids (2). The
      eleven Cabernet Sauvignon wines varied greatly in their chemical composition.
      Nine yeast strains completed alcoholic fermentation in 19 days; S. bayanus AWRI
      1375 in 26 days, and S. cerevisiae AWRI 1554 required 32 days. Ethanol
      concentrations varied in the final wines (12.7-14.2 %). The two S. bayanus
      strains produced the most distinct wines, with the ability to metabolise malic
      acid, generate high glycerol concentrations and distinctive phenolic composition.
      Saccharomyces hybrid AWRI 1501 and S. cerevisiae AWRI 1554 and AWRI 1493 also
      generated distinctive wines. This work demonstrates that the style of a Cabernet
      Sauvignon can be clearly modulated by choice of commercially available wine
      yeast.

PMID- 22878904
TI  - Subacute anterior horn disease caused by neuroborreliosis.

PMID- 22878905
TI  - Effects of cerebrolysin administration on oxidative stress-induced apoptosis in
      lymphocytes from CADASIL patients.
AB  - Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties
      which has been used to treat dementia and sequelae of stroke. Use of Cere
      prevents nuclear structural changes typical of apoptosis and significantly
      reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral
      Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
      (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding
      the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating
      Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the
      in vitro protective effects of Cere against oxidative stress-induced apoptosis in
      cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15
      CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly
      reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was
      analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to
      PBLs from CADASIL patients cultured under standard conditions had no effect on
      the percentage of apoptotic cells. Administration of Cere to PBLs cultured with
      dRib caused a significant decrease in apoptosis after 48 h of culture in only 5
      patients, whereas in the other 10 patients, Cere treatment was not associated
      with any significant difference in the percentage of apoptosis. This result
      showed a protective effect of Cere against oxidative stress-induced apoptosis
      only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably
      does not influence the anti-apoptotic properties of Cere in vitro.

PMID- 22878906
TI  - Trace elements and oxidative stress in hypertensive disorders of pregnancy.
AB  - PURPOSE: Due to increased metabolic requests, pregnancy can be considered as
      metabolic stress, especially if associated with oxidative stress triggered by
      disbalance of pro/antioxidants. The aim of the study was to determine serum
      concentrations of the trace elements iron (Fe), zinc (Zn) and copper (Cu)
      important in growth regulation and pro/anti-oxidant homeostasis, in relation to
      the total serum oxidant capacity (TOC) and total serum antioxidant capacity (TAC)
      in pregnant women with preeclampsia (n = 30) or with gestational hypertension (n
      = 30) and in healthy pregnant women (n = 37) and non-pregnant women (n = 30) as
      control groups expecting common differences between all pregnant women and
      controls and between preeclampsia and the other pregnancies indicating specific
      disbalance of the oxidative stress and analyzed trace elements. METHODS: Serum Fe
      was determined by spectrophotometric method, Cu and Zn were determined by atomic
      absorption spectrometry, TOC was determined by Enzymatic ANTIOX-CAP assay and TAC
      by Peroxide-activity assay. RESULTS: Serum Cu and TOC were significantly higher
      while Zn was lower in all pregnant groups regardless of hypertensive disorders.
      Serum Fe and TAC concentrations were found to be significantly higher in pregnant
      women with preeclampsia compared to pregnant controls. CONCLUSION: Increase of
      TOC in all pregnant women our study points to latent oxidative stress in
      pregnancy. Fe might have a role in etiopathogenesis of preeclampsia while the
      increase of TAC in the very beginning of preeclampsia might represent a
      stressdefence mechanism of the body. It has still to be revealed whether
      significantly higher serum Fe levels are associated with preeclampsia as a cause
      or as a consequence of this disorder.

PMID- 22878907
TI  - Could maternal pre-pregnancy body mass index affect Apgar score?
AB  - OBJECTIVE: Obesity is one of global health problems and maternal obesity may be
      associated with increase in risk of pregnancy complications and neonatal death.
      The purpose of this study was to evaluate the effect of maternal pre-pregnancy
      body mass index (BMI) on neonate Apgar score at minute 5. METHODS: In a
      retrospective cohort study, Apgar score at minute 5 of all singleton term babies
      of nulliparous women whom were delivered in Shahid Sadoughi Hospital, Yazd, Iran,
      from 2007 to 2009 were evaluated. Body mass index (BMI: weight in kg/height in
      m(2)) of the mothers were calculated and BMI less than 18.5, 18.5-24.9, 25-29.9
      and more than 30 were considered underweight, normal, overweight and obesity,
      respectively. Neonatal Apgar score of 3-7 and less than three was considered as
      low and very low Apgar score, respectively. RESULTS: Eighty-eight (2.8 %) women
      were underweight, 1,401 (44.9 %) normal weight, 1,389 (44.5 %) overweight and 242
      (7.8 %) were obese. 477 (15.3 %) and 31(0.7 %) neonates had low and very low
      Apgar score, respectively at minute 5. Logistic regression analysis showed
      maternal overweight [in odd ratio of 3.7, 95 % CI 2.4-4.6] and obesity [in odd
      ratio of 13.4, 95 % CI 9.7-14.1] were risk factors of neonatal low Apgar score,
      but they had not any statistically significant effect on neonatal very low Apgar
      score. CONCLUSION: Maternal pre-pregnancy overweight should be more concerned to
      prevent complication of low Apgar score in their newborns.

PMID- 22878908
TI  - Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers
      independently of the TZD effects on aromatase.
AB  - Thiazolidinediones (TZDs) are insulin sensitizers used for treatment of diabetes.
      We have previously reported that TZDs reduce estrogen synthesis by inhibiting
      aromatase activity in human granulosa cells (HGC). Multiple clinical trials
      demonstrated that TZDs increase the risk of fractures in postmenopausal women
      with type 2 diabetes. We studied mouse osteoblasts alone or in a co-culture with
      HGC to determine whether TZD inhibition of aromatase plays a role in their
      effects on bone metabolism. Mouse osteoblasts were cultured with and without HGC,
      and incubated in a medium with or without testosterone, pioglitazone or
      rosiglitazone. Cell growth, oleic acid uptake, alkaline phosphatase activity, and
      osteocalcin production were measured. TZDs inhibited estradiol production by up
      to 84% in HGC/mouse osteoblast co-cultures. TZDs induced mouse osteoblast death
      and increased oleic acid uptake. TZDs also inhibited alkaline phosphatase
      activity (58-75%, p<0.046) and osteocalcin production (52-75%, p<0.031). For all
      the parameters, there were no significant differences between the osteoblast
      cultures alone and the HCG/osteoblast co-cultures. TZD effects on osteoblast
      viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are
      independent of their effects on aromatase.

PMID- 22878909
TI  - Surgical treatment of chronic groin pain in athletes.
AB  - PURPOSE: Conservative treatment of chronic groin pain is prolonged and recurrence
      is quite common. Coexistence of sports hernia and adductor tendinitis/tendinosis
      in a single patient is noted in the literature. In our study we evaluated our
      operative treatment that should enable pain elimination and fast return to sports
      activities. METHODS: We performed a prospective study over a six-year period.
      Ninety-nine (99) patients, all male, with chronic groin pain, resistant to
      conservative treatment, underwent a surgical procedure. RESULTS: Seventy athletes
      with sports hernia returned to sports in an average 4.23 weeks (range three-16).
      Adductor tendinosis symptoms were present in 24 patients (2 %) with sports
      hernia. Twenty-four patients that had an additional adductor tenotomy performed
      returned to sports in an average 11.6 weeks (range ten-15). Five patients with
      isolated adductor tendinosis (7 %) returned to sports in an average 13.4 weeks
      (range 12-16). All athletes except two (2.8 %) treated for sports hernia were
      satisfied with the results of treatment and could continue their previous level
      of activity. CONCLUSION: Any surgical procedure used for treating chronic groin
      pain should address the common causes of pain in this region. Adductor tendinosis
      can be present in up to 24.2 % of cases with sports hernia or may be isolated in
      7 % of cases with chronic groin pain and must be treated by tenotomy. Resection
      of the genital branch of genitofemoral nerve and ilioinguinal nerve neurolysis
      should also be performed in patients with sports hernia.

PMID- 22878910
TI  - Light microscopic histology of quadriceps tendon ruptures.
AB  - PURPOSE: To assess histological changes and possible differences in the
      quadriceps of patients undergoing open repair of the tendon after spontaneous
      rupture, and subjects with no history of tendon pathology. MATERIALS: Biopsies
      were harvested from the quadriceps tendon of 46 patients (34 men, 12 women) who
      had reported unilateral atraumatic quadriceps tendon rupture and had undergone
      surgical repair of the tendon. Samples were also harvested from both the tendons
      in 11 (N = 11 * 2) patients, nine males and two females, dying from
      cardiovascular disorders. For each tendon, three slides were randomly selected
      and examined under light microscopy, and assessed using a semiquantitative
      grading scale (range 0-21) which considers fibre structure, fibre arrangement,
      rounding of the nuclei, regional variations in cellularity, increased
      vascularity, decreased collagen stainability, and hyalinisation. RESULTS: The
      pathological sum-score averaged 19.2 +/- 3.7 in ruptured tendons and 5.6 +/- 2.0
      in controls, and all variables considered were significantly different between
      the two groups, showing an association between tendon abnormalities and rupture
      (0.05 < P < 0.001). CONCLUSION: This study confirms that the presence of
      histological degenerative changes in torn quadriceps tendons increases the risk
      of rupture.

PMID- 22878911
TI  - Cancer screening at a federally qualified health center: a qualitative study on
      organizational challenges in the era of the patient-centered medical home.
AB  - Federally Qualified Health Centers (FQHCs) serve uninsured and minority
      populations, who have low cancer screening rates. The patient-centered medical
      home (PCMH) model aims to provide comprehensive preventive services, including
      cancer screening, to these populations. Little is known about organizational
      factors influencing the delivery of cancer screening in this context. We
      conducted 18 semi-structured interviews with clinic personnel at four FQHC
      clinics in Washington State. All interviews were recorded and transcribed
      verbatim and analyzed by two bilingual coders to identify salient themes. We
      found that screening on-site, scheduling separate visits for preventive care, and
      having non-provider staff recommend and schedule screening services facilitated
      the delivery of cancer screening. We found work overload to be a barrier to
      screening. To successfully implement screening strategies within the PCMH model,
      FQHCs must enhance facilitators and address organizational gaps in their cancer
      screening processes. 

PMID- 22878912
TI  - Angioneural crosstalk in scaffolds with oriented microchannels for regenerative
      spinal cord injury repair.
AB  - The aim of our work is to utilize the crosstalk between the vascular and the
      neuronal system to enhance directed neuritogenesis in uniaxial guidance scaffolds
      for the repair of spinal cord injury. In this study, we describe a method for
      angioneural regenerative engineering, i.e., for generating biodegradable
      scaffolds, produced by a combination of controlled freezing (freeze-casting) and
      lyophilization, which contain longitudinally oriented channels, and provide
      uniaxial directionality to support and guide neuritogenesis from neuronal cells
      in the presence of endothelial cells. The optimized scaffolds, composed of 2.5 %
      gelatin and 1 % genipin crosslinked, were characterized by an elastic modulus of
      ~51 kPa and longitudinal channels of ~50 MUm diameter. The scaffolds support the
      growth of endothelial cells, undifferentiated or NGF-differentiated PC12 cells,
      and primary cultures of fetal chick forebrain neurons. The angioneural crosstalk,
      as generated by first forming endothelial cell monolayers in the scaffolds
      followed by injection of neuronal cells, leads to the outgrowth of long aligned
      neurites in the PC12/endothelial cell co-cultures also in the absence of
      exogenously added nerve growth factor. Neuritogenesis was not observed in the
      scaffolds in the absence of the endothelial cells. This methodology is a
      promising approach for neural tissue engineering and may be applicable for
      regenerative spinal cord injury repair.

PMID- 22878914
TI  - Graciloplasty for recurrent recto-neovaginal fistula in a male-to-female
      transsexual.
AB  - Rectovaginal fistula is usually a challenging condition for surgeons, but a
      fistula between the rectum and the neovagina in male-to-female transsexual is
      even more difficult to treat as it is a rare complication occurring in a patient
      with modified anatomy of the perineum, with heavy psychological implications for
      the patient. Here, we report a case of recurrent recto-neovaginal fistula in a
      male-to-female transsexual successfully treated by perineal graciloplasty.

PMID- 22878913
TI  - Expression profile of flotillin-2 and its pathophysiological role after spinal
      cord injury.
AB  - Some receptors that block axonal regeneration or promote cell death after spinal
      cord injury (SCI) are localized in membrane rafts. Flotillin-2 (Flot-2) is an
      essential protein associated with the formation of these domains and the
      clustering of membranal proteins, which may have signaling activities. Our
      hypothesis is that trauma will change Flot-2 expression and interference of this
      lipid raft marker will promote functional locomotor recovery after SCI. Analyses
      were conducted to determine the spatiotemporal profile of Flot-2 expression in
      adult rats after SCI, using the MASCIS impactor device. Immunoblots showed that
      SCI produced a significant decrease in the level of Flot-2 at 2 days post-injury
      (DPI) that increased until 28 DPI. Confocal microscopy revealed Flot-2 expression
      in neurons, reactive astrocytes and oligodendrocytes specifically associated to
      myelin structures near or close to the axons of the cord. In the open field test
      and grid walking assays, to monitor locomotor recovery of injured rats infused
      intrathecally with Flot-2 antisense oligonucleotides for 28 days showed
      significant behavioral improvement at 14, 21 and 28 DPI. These findings suggest
      that Flot-2 has a role in the nonpermissive environment that blocks locomotor
      recovery after SCI by clustering unfavorable proteins in membrane rafts.

PMID- 22878916
TI  - Effective intra-esophageal acid control is associated with improved
      radiofrequency ablation outcomes in Barrett's esophagus.
AB  - BACKGROUND: Endoscopic radiofrequency ablation (RFA) is a promising new treatment
      of Barrett's esophagus (BE). Adjunctive intra-esophageal pH control with proton
      pump inhibitors and/or anti-reflux surgery is generally recommended to optimize
      squamous re-epithelialization after ablation. AIMS: The aims of this study were
      to examine the association between intra-esophageal pH control and RFA outcomes
      and to identify predictive factors to achieve complete elimination (CE) of BE
      following RFA. METHODS: We retrospectively studied the outcomes of BE patients
      treated with RFA. Esophageal acid exposure (EAE) was assessed utilizing 24-h pH
      monitoring on therapy. CE was endoscopically defined as no area suspicious for
      residual metaplasia following RFA. RESULTS: Of 45 patients (33 men; mean age
      61.6, mean BE length C4.1 M4.6) examined for EAE, 29 % exhibited moderate-severe
      EAE despite therapy. Reduction in BE surface area and CE rate were higher in the
      normal-mild EAE group compared with the moderate-severe EAE group (99 vs. 95 %, p
      = 0.02; 44 vs. 15 %, p = 0.09, respectively). Using univariate analysis, age,
      gender, race, aspirin/NSAIDs use, baseline worst histology, baseline BE surface
      area, and the number or types of RFA had no correlation with CE. By multivariate
      multiple logistic regression analysis, normal-mild EAE and smaller hiatal hernia
      were independent factors associated with CE. CONCLUSIONS: Effective intra
      esophageal pH control is associated with improved RFA outcomes of BE. Normal to
      mild EAE and smaller hiatal hernia are predictive factors to achieve CE. Given
      the frequent persistence of acid reflux despite therapy in BE patients, in order
      to maximize the RFA effects esophageal pH optimization and hernia repair should
      be considered.

PMID- 22878915
TI  - Neuroprotective effect of quercetin on the duodenum enteric nervous system of
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: In diabetes mellitus (DM), hyperglycemia promotes changes in
      biochemical mechanisms that induce oxidative stress. Oxidative stress has been
      closely linked to adverse consequences that affect the function of the
      gastrointestinal tract caused by injuries to the enteric nervous system (ENS)
      that in turn cause neurodegeneration and enteric glial loss. Therapeutic
      approaches have shown that diet supplementation with antioxidants, such as
      quercetin, reduce oxidative stress. AIMS: This work sought to evaluate neurons
      and enteric glial cells in the myenteric and submucosal plexuses of the duodenum
      in diabetic rats supplemented with quercetin. METHODS: The duodenum of 24 rats,
      including a control group (C), control quercetin supplementation group (CQ),
      diabetic group (D), and diabetic quercetin supplementation group (DQ), were used
      to investigate whole mounts of muscular and submucosal layers subjected to
      immunohistochemistry to detect vasoactive intestinal peptide in the myenteric
      layer and double-staining for HuC-D/neuronal nitric oxide synthase (nNOS) and HuC
      D/S100. RESULTS: A reduction of the general neuronal population (HuC/D) was found
      in the myenteric and submucosal plexuses (p < 0.001) in the D and DQ groups. The
      nitrergic subpopulation (nNOS) decreased only in the myenteric plexus (p <
      0.001), and glial cells decreased in both plexuses (p < 0.001) in the D and DQ
      groups. In diabetic rats, quercetin supplementation reduced neuronal and glial
      loss. Diabetes promoted an increase in the cell body area of both the general and
      nitrergic populations. Quercetin supplementation only prevented neuronal
      hypertrophy in the general population. CONCLUSION: Supplementation with quercetin
      eased the damage caused by diabetes, promoting a neuroprotective effect and
      reducing enteric glial loss in the duodenum.

PMID- 22878917
TI  - Not all side population cells contain cancer stem-like cells in human gastric
      cancer cell lines.
AB  - INTRODUCTION: Side population (SP) cells may play a crucial role in tumorigenesis
      and the recurrence of cancer. Many kinds of cell lines and tissue have
      demonstrated presence of SP cells including different gastric cancer cell lines.
      However, is that true all SP cells contain cancer stem-like cells in gastric
      cancer cell lines? MATERIALS AND METHODS: MKN-45 and BGC-823 cells labeled with
      Hoechst 33342 were chosen to obtain SP cells, then characterized the cancer stem
      like properties of SP cells both in vitro and in vivo. Five stemness-related
      genes expression profiles, including OCT-4, SOX-2, NANOG, CD44 and ATP-binding
      cassette transporters gene ABCG-2, were tested in SP and MP cells using
      quantitative real-time RT-PCR. Western blot was chosen to show the difference of
      protein expression between SP and MP cells. When inoculated into non-obese
      diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells from MKN-45
      showed higher tumorigenesis tendency than MP cells, but SP cells from BGC-823
      showed same tumorgenesis tendency as MP cells. CONCLUSION: SP cells from MKN-45
      possess cancer stem cell properties and proved that they were gastric cancer stem
      like cells. SP cells from BGC-823 didn't possess cancer stem cell properties and
      proved that not all SP cells contain cancer stem-like cells in gastric cancer
      cell lines.

PMID- 22878919
TI  - Impacting cancer survivorship.

PMID- 22878918
TI  - Probucol ameliorates the development of nonalcoholic steatohepatitis in rats fed
      high-fat diets.
AB  - AIMS: We sought to evaluate the effects of probucol on steatohepatitis and
      associated molecular mechanisms in a rat model of nonalcoholic steatohepatitis
      (NASH) induced by high-fat diet (HFD). METHODS: Forty male rats weighing 100-120
      g were randomly assigned to the following treatments (n = 10 for each treatment):
      standard diet + normal saline (NC group), standard diet + 500 mg/kg/day probucol
      (NP group), HFD + normal saline (HD group), and HFD + 500 mg/kg/day probucol (HP
      group). All animals received the above treatments for 15 weeks. Lipid metabolism
      and steatohepatitis were assessed. Systemic insulin resistance, oxidative stress
      status, serum tumor necrosis factor-alpha (TNF-alpha) and adiponectin levels, and
      gene expression were examined. RESULTS: High-fat feeding resulted in
      macrovesicular steatosis, lobular inflammation, and hepatocellular ballooning
      degeneration in the liver, coupled with increased concentrations of serum
      aspartate aminotransferase and alanine aminotransferase. Probucol exposure
      attenuated the biochemical and histological changes comparable with NASH.
      Moreover, probucol treatment significantly prevented the elevations of serum
      total cholesterol, low-density lipoprotein, and high-density lipoprotein and the
      increase in the expression of numerous lipid metabolism-related genes in HFD-fed
      rats. There were increased insulin sensitivity and serum adiponectin levels and
      enhanced hepatic AMP-activated protein kinase phosphorylation in the HP group.
      Probucol lessened the HFD-induced elevation of serum TNF-alpha and hepatic
      malondialdehyde and reduced antioxidant enzymatic activities. CONCLUSIONS:
      Probucol shows beneficial effects on HFD-induced steatohepatitis by improving
      insulin resistance and attenuating oxidative stress and systemic inflammation.

PMID- 22878920
TI  - Vasodilation and hypotension of CZ454, an analogue of lacidipine through
      inhibiting extracellular calcium influx.
AB  - The aim of this study was to evaluate the effects of an analogue of lacidipine,
      CZ454 in in vitro and in vivo. The isometric tension of Sprague-Dawley rat
      arterial ring segments was recorded by a myography system. Intracellular calcium
      of vascular smooth muscle was determined by the confocal laser microscopy. Blood
      pressure of spontaneously hypertensive rats was measured using a tail-cuff blood
      pressure system. The results showed that CZ454 (10 - 9-10 - 6 mol/L) relaxed the
      mesenteric artery contracted by high K +  concentration-dependently, which was
      not affected by removal of the endothelium. CZ454 treatment shifted the
      concentration-contractile curves induced by phenylephrine, U46619, KCl and CaCl2
      to the right with the decreased Emax. CZ454 was more potent in the coronary and
      basilar artery than in the mesenteric artery. CZ454 did not reduce phenylephrine
      induced vasoconstriction; however, it did inhibit the contraction caused by
      addition of CaCl2 and did not change caffeine-induced contraction in the
      mesenteric artery in Ca2 + -free solution. CZ454 decreased the vasoconstriction
      induced by Bay K 8644 in the presence of 60 mmol/L K + . CZ454 1.0 mg/kg
      administered by gavage lowered the systolic pressure and diastolic pressure by
      20% and 17%, respectively. It was concluded that CZ454 lowers blood pressure and
      relaxes arteries with higher potency in coronary and basilar artery and that the
      vasodilation may involve inhibition of calcium influx.

PMID- 22878921
TI  - An in vivo evaluation of cerebral cortical amyloid with [18F]flutemetamol using
      positron emission tomography compared with parietal biopsy samples in living
      normal pressure hydrocephalus patients.
AB  - PURPOSE: The primary objectives of this study were to assess the safety of
      [(18)F]flutemetamol injection and determine the level of association between the
      quantitative estimates of brain uptake of [(18)F]flutemetamol and the
      quantitative immunohistochemical (IHC) estimates of amyloid levels in cerebral
      cortex biopsies obtained during shunt placement in patients with normal pressure
      hydrocephalus (NPH). PROCEDURES: Parietal lobe biopsies were obtained from 12
      subjects (mean (SD), 71 (8.1) years), during shunt placement for NPH. Shunt
      procedures and biopsies were performed within 8 weeks after the positron emission
      tomography (PET) imaging, and followed by a computed tomography scan. The
      quantitative estimates of the brain uptake of [(18)F]flutemetamol (standard
      uptake value ratios (SUVRs)) from the biopsy site, contralateral to the biopsy
      site, and composite were made from the analysis of PET images. The quantitative
      IHC levels of amyloid load were estimated using a monoclonal antiamyloid beta
      antibody, 4 G8 (in percent area), as the standard of truth (N = 8, of which 5 had
      full histopathology staining). The primary analysis determined the level of
      association between the SUVR (with cerebellum as the reference region) from the
      biopsy site, and the level of amyloid was determined from IHC estimates of
      amyloid in the biopsy sample. RESULTS: [(18)F]Flutemetamol injection was found to
      be well tolerated. The biopsied area well represented the amyloid deposition
      throughout the cortex in this small sample. The biopsy site SUVR was
      significantly correlated with the biopsy specimen amyloid beta level (expressed
      as percent of biopsy specimen area staining with 4 G8). The full model was
      significant (p = 0.0174). In the secondary efficacy analyses, contralateral (to
      biopsy site) and composite SUVR values correlated significantly with the percent
      of biopsy specimen staining for amyloid beta based on 4 G8. Blinded visual
      [(18)F]flutemetamol image interpretations showed a sensitivity of 100 % and a
      specificity of 100 % with pathology reads staining for amyloid plaque with
      Bielschowsky and thioflavin S and overall pathology read. The results of the
      blinded reader agreement for [(18)F]flutemetamol PET showed full agreement among
      three readers. CONCLUSIONS: PET imaging of NPH patients following the
      administration of [(18)F]flutemetamol injection was highly correlated with the
      presence of fibrillar amyloid beta in subsequent cortical biopsy samples in this
      small sample. Administration of [(18)F]flutemetamol injection was well tolerated.

PMID- 22878922
TI  - Rescue of internalization-defective platelet-activating factor receptor function
      by EBP50/NHERF1.
AB  - Platelet-activating factor (PAF) is a potent phospholipid mediator involved in
      specific disease states such as allergic asthma, atherosclerosis and psoriasis.
      The human PAF receptor (PAFR) is a member of the G protein-coupled receptor
      (GPCR) family. Following PAF stimulation, cells become rapidly desensitized; this
      refractory state can be maintained for hours and is dependent on PAFR
      phosphorylation, internalization and trafficking. EBP50/NHERF1 has been found to
      interact with a variety of proteins and these interactions are involved in a
      growing range of functions including the assembly of signalling complexes,
      receptor recycling and transport of proteins to the cell surface. Crucial roles
      of EBP50 in GPCR physiology include its involvement in internalization,
      recycling, and downregulation. We were interested in identifying the role of
      EBP50 in PAFR trafficking. Our results showed that EBP50 binds the PAFR in its
      basal state, while stimulation decreased the ratio of interaction between the two
      proteins. We also demonstrated that EBP50 could bind PAFR via its PDZ 2 domain.
      In addition, we studied the role of EBP50 in various functions of the PAFR such
      as PAF-induced inositol phosphate accumulation and receptor internalization:
      EBP50 decreased the WT PAFR response and rescued the function of internalization
      deficient mutant receptors, as previously described for the arrestins and the
      GRKs. These results suggest new roles for EBP50, some of which could help
      understanding the complex formation after receptor activation.

PMID- 22878923
TI  - On the designing of a tamper resistant prescription RFID access control system.
AB  - Recently, Chen et al. have proposed a novel tamper resistant prescription RFID
      access control system, published in the Journal of Medical Systems. In this paper
      we consider the security of the proposed protocol and identify some existing
      weaknesses. The main attack is a reader impersonation attack which allows an
      active adversary to impersonate a legitimate doctor, e.g. the patient's doctor,
      to access the patient's tag and change the patient prescription. The presented
      attack is quite efficient. To impersonate a doctor, the adversary should
      eavesdrop one session between the doctor and the patient's tag and then she can
      impersonate the doctor with the success probability of '1'. In addition, we
      present efficient reader-tag to back-end database impersonation, de
      synchronization and traceability attacks against the protocol. Finally, we
      propose an improved version of protocol which is more efficient compared to the
      original protocol while provides the desired security against the presented
      attacks.

PMID- 22878924
TI  - Secondary aortoesophageal fistula after thoracic endovascular aortic repair for a
      huge aneurysm.
AB  - Thoracic endovascular aortic repair for a descending thoracic aortic aneurysm is
      an excellent alternative to open surgery, especially in patients with a number of
      comorbidities. It may cause fatal complications, including aortoesophageal
      fistula, but these are very rare. Here, we report the case of secondary
      aortoesophageal fistula four months after the procedure for a huge descending
      thoracic aortic aneurysm, which presented with new-onset high-grade fever
      accompanied by elevated inflammatory markers.

PMID- 22878925
TI  - Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation
      following peripheral nerve injury.
AB  - Accumulating evidence indicates that activation of spinal cord microglia plays an
      important role in the genesis of neuropathic pain. Resolvin E1 (E1) is derived
      from omega-3 polyunsaturated fatty acid and exhibits potent anti-inflammatory,
      pro-resolution, and anti-nociceptive effects. We further examined whether RvE1
      could reduce neuropathic pain and modulate spinal cord microglial activation.
      Intrathecal pre-treatment of RvE1 (100 ng) daily for 3 days partially prevented
      the development of nerve injury-induced mechanical allodynia and up-regulation of
      IBA-1 (microglial marker) and TNF-alpha in the spinal cord dorsal horn.
      Furthermore, intrathecal post-treatment of RvE1 (100 ng), 3 weeks after nerve
      injury, transiently reduced mechanical allodynia and heat hyperalgesia. Finally,
      RvE1 blocked lipopolisaccharide-induced microgliosis and TNF-alpha release in
      primary micoglial cultures. Our data suggest that RvE1 may attenuate neuropathic
      pain via inhibiting microglial signaling. Targeting the anti-inflammatory and pro
      resolution lipid mediators may offer new options for preventing and treating
      neuropathic pain.

PMID- 22878926
TI  - Vascular disrupting activity and the mechanism of action of EHT 6706, a novel
      anticancer tubulin polymerization inhibitor.
AB  - Tumor blood vessels are an important emerging target for anticancer therapy.
      Here, we characterize the in vitro antiproliferative and antiangiogenic
      properties of the synthetic small molecule, 7-ethoxy-4-(3,4,5
      trimethoxybenzyl)isoquinolin-8-amine dihydrochloride, EHT 6706, a novel
      microtubule-disrupting agent that targets the colchicine-binding site to inhibit
      tubulin polymerization. At low nM concentrations, EHT 6706 exhibits highly potent
      antiproliferative activity on more than 60 human tumor cell lines, even those
      described as being drug resistant. EHT 6706 also shows strong efficacy as a
      vascular-disrupting agent, since it prevents endothelial cell tube formation and
      disrupts pre-established vessels, changes the permeability of endothelial cell
      monolayers and inhibits endothelial cell migration. Genome-wide transcriptomic
      analysis of EHT 6706 effects on human endothelial cells shows that the
      antiangiogenic activity elicits gene deregulations of antiangiogenic pathways.
      These findings indicate that EHT 6706 is a promising tubulin-binding compound
      with potentially broad clinical antitumor efficacy.

PMID- 22878927
TI  - Analysis of direct medical and nonmedical costs for care of rheumatoid arthritis
      patients using the large cohort database, IORRA.
AB  - OBJECTIVES: Our goal was to determine the annual direct medical and nonmedical
      costs for the care of patients with rheumatoid arthritis (RA) using data from a
      large cohort database in Japan. METHODS: Direct medical costs [out of pocket to
      hospitals and pharmacies and for complementary and alternative medicine (CAM)]
      and nonmedical costs (caregiving, transportation, self-help devices, house
      modifications) were determined for RA patients who were participants in the
      Institute of Rheumatology, Rheumatoid Arthritis (IORRA) studies conducted in
      October 2007 and April 2008. Correlations between these costs and RA disease
      activity, disability level, and quality of life (QOL) were assessed. RESULTS:
      Data were analyzed from 5,204 and 5,265 RA patients in October 2007 and April
      2008, respectively. The annual direct medical costs were JPY132,000 [out of
      pocket to hospital (US$1 = JPY90 in 2007)], JPY84,000 (out of pocket to
      pharmacy), and JPY146,000 (CAM). Annual direct nonmedical costs were JPY105,000
      (caregiving), JPY22,000 (transportation), JPY30,000 (self-help devices), and
      JPY188,000 (house modifications). Based on the utilization rate for each cost
      component, the annual medical and nonmedical costs for each RA patient were
      JPY262,136 and JPY61,441, respectively. Costs increased with increasing RA
      disease activity and disability level or worsening quality of life (QOL).
      CONCLUSIONS: Based on the IORRA database, patients with RA bear heavy economic
      burdens that increase as the disease is exacerbated. The results also suggest
      that the increase in medical and nonmedical costs may be ameliorated by the
      proactive control of disease activity.

PMID- 22878928
TI  - Exposure to cats: update on risks for sensitization and allergic diseases.
AB  - Cats are the pets most commonly implicated in the etiology of asthma and allergic
      disease. However, systematic reviews have concluded that there is a lack of
      evidence to support the idea that cat exposure in early life increases the risk
      of allergic disease. Indeed, it appears most likely that cat exposure is
      protective against allergic diseases. Recent large prospective studies have shown
      that living with a cat during childhood, especially during the first year of a
      child's life, could be protective. However, any advice given to the parents
      should also incorporate how new acquisition of cats can affect other family
      members, especially those who are already sensitized. Research is urgently needed
      to determine whether the suggested impact of acquisition of cats in adult life is
      modified by the person's childhood pet ownership, to help parents who seek advice
      on whether or not to get a cat.

PMID- 22878929
TI  - Integrated Management of Neonatal and Childhood Illness (IMNCI): skill assessment
      of health and Integrated Child Development Scheme (ICDS) workers to classify sick
      under-five children.
AB  - OBJECTIVE: To assess the skills (diagnostic/counseling) of Integrated Management
      of Neonatal and Childhood Illness (IMNCI) trained workers; and to assess the
      degree of agreement between the physician and the IMNCI trained workers of
      Raipurrani block, district Panchkula, India, to classify sick under-five children
      in field. METHODS: The cross-sectional study was conducted in Raipurrani in the
      outpatient departments of the community health centre and one primary health
      centre in 2010. Workers from health department and Integrated Child Development
      Scheme (ICDS) were assessed in this study. They received IMNCI training in 2006,
      with 1 day refresher training in 2009. Investigator noted his observations using
      a skill assessment checklist. Under-five child observations were the unit of
      study. RESULTS: Sixteen IMNCI trained workers made 128 child observations.
      Considering color-coded categorization under IMNCI, agreement with investigator
      (Kappa) was intermediate; red and yellow categorizations had poor agreement.
      Morbidity-wise agreement (Kappa) was poor for possible serious bacterial
      infection, feeding problem, respiratory problem and anemia. Considering final
      diagnosis, investigator and IMNCI trained worker completely agreed in 45 % child
      observations. All symptoms were asked only in 15 %. Skills were poor overall for
      young infants. For children between 2 mo to 5 y, danger signs, neck stiffness,
      edema, wasting and pallor were checked in <40 % observations. Immunization card
      was asked for in 20 % observations. IMNCI trained workers performed well in all
      aspects of counseling, except follow up. CONCLUSIONS: Training without effective
      implementation plans will not result in long term skill retention.

PMID- 22878930
TI  - Molecular characterisation and prenatal diagnosis of Asparto-acylase deficiency
      (Canavan disease)--report of two novel and two known mutations from the Indian
      subcontinent.
AB  - OBJECTIVES: To establish a technique for mutation identification and prenatal
      screening in confirmed cases of Canavan disease. METHOD: Mutations in ASPA gene
      were identified by sequencing. Six exons of ASPA gene were amplified using
      intronic primers flanking the exons and then sequenced on ABI 3500Dx automated
      unit. This technique was used to identify mutations in three cases of Canavan
      disease. Prenatal diagnosis was performed in two families. RESULTS: Two reported
      mutations c.162 C > A (p.Asn54Lys) and c.859 G > A (p.Ala287Thr) were identified
      in two different cases of Canavan disease. Third case was compound heterozygous
      for two novel mutations (c.728 T > G, p.Ile243Ser; c.902 T > C, p.Leu301Pro).
      Prenatal diagnosis was performed in three pregnancies in two families, two
      affected fetuses and one unaffected fetus were identified. CONCLUSIONS: Molecular
      characterization of Canavan disease helps identify the cause at genetic level,
      thus confirming diagnosis and enabling identification of carriers in the family.
      Though enzyme assay and NAA measurement allows diagnosis and prenatal diagnosis
      of Canavan diasease, molecular methods have the advantage of bringing accuracy in
      prenatal testing with an earlier result. This is the first case report of
      mutation studies in Canavan disease from Indian subcontinent.

PMID- 22878931
TI  - Probing L-pyruvate kinase regulatory phosphorylation site by mutagenesis.
AB  - The activity of L-type pyruvate kinase (L-PK, ATP:pyruvate 2-O
      phosphotransferase, EC 2.7.1.40) is regulated by phosphorylation of serine
      residue 12 of the N-terminal regulatory domain MEGPAGYLRR(10)AS ( 12
      )VAQLTQEL(20)GTAFF of the protein. In this report we studied the effect of the
      point mutations around this phosphorylation site on the catalytic properties of
      this enzyme, by introducing amino acids A, L, K, Q and E into positions 9, 10 and
      13 of this peptide sequence. It was found that some of these mutations in
      positions 9 and 10, although occurring at great distances from the enzyme's
      active site, affected the enzyme's activity by decreasing the effectiveness of
      phosphoenolpyruvate binding (PEP) with the enzyme, but had practically no
      influence on the binding effectiveness of the second substrate ADP. A similar
      asymmetric effect on the binding of these substrates was previously observed
      after phosphorylation of the enzyme regulatory N-domain peptide, and also after
      proteolytic truncation of the same N-terminal part of L-PK. All these results
      could be explained by the internal complex formation between the N-domain peptide
      and the enzyme's main body. The present study delineated the specificity of the
      internal binding site and revealed the possibility that the regulatory effect
      could be modulated by selecting mutation sites and amino acids introduced into
      the N-terminal domain structure.

PMID- 22878933
TI  - Municipal solid waste landfill site selection with geographic information systems
      and analytical hierarchy process: a case study in Mahshahr County, Iran.
AB  - Landfill siting is a complicated process because it must combine social,
      environmental and technical factors. In this study, in order to consider all
      factors and rating criteria, a combination of geographic information systems and
      analytical hierarchy process (AHP) was used to determine the best sites for
      disposal of municipal solid waste (MSW) in Mahshahr County, Iran. In order to the
      decision making for landfill siting a structural hierarchy formed and the most
      important criteria: surface water, sensitive ecosystems, land cover, urban and
      rural areas, land uses, distance to roads, slope and land type were chosen
      according to standards and regulations. Each criterion was evaluated by rating
      methods. In the next step the relative importance of criteria to each other was
      determined by AHP. Land suitability for landfill was evaluated by simple additive
      weighting method. According to the landfill suitability map, the study area
      classified to four categories: high, moderate, low and very low suitability
      areas, which represented 18.6%, 20.3%, 1.6 and 0.8% of the study area
      respectively. The other 58.7% of the study area was determined to be completely
      unsuitable for landfill. By considering the parameters, such as the required area
      for landfill, distance to MSW generation points, and political and management
      issues, and consulting with municipalities managers in the study area, six sites
      were chosen for site visiting. The result of field study showed that it is a
      supplementary, and necessary, step in finding the best candidate landfill site
      from land with high suitability.

PMID- 22878932
TI  - Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis
      infection in mice.
AB  - The aim of the study is to investigate the immunological changes after
      stimulation with bacillus Calmette-Guerin (BCG) in mice with vitamin D
      deficiency. After weaning, mice were divided into the vitamin D-deficient group (
      D group), the normal group (N group), and the vitamin D-supplemented group (+D
      group). Twelve-week-old mice were intraperitoneally injected with 0.5 mg/ml BCG
      (>=1.0 * 10(6) CFU/mg) and maintained for 6 weeks. Spleen lymphocytes were
      isolated, and the percentages of CD4(+) and CD8(+) lymphocytes were determined by
      flow cytometry. IFN-gamma levels, IL-10 levels, and the TB-PPD-specific antibody
      titer were determined by ELISA. The inter-group difference was analyzed using one
      way ANOVA, and multiple comparisons were analyzed using the LSD test. The
      percentage of CD4(+) cells was 27.1 +/- 0.6 in the -D group, 23.62 +/- 0.42 in
      the N group, and 19.46 +/- 0.32 in the +D group (P < 0.05). The percentage of
      CD8(+) lymphocytes was 12.15 +/- 0.61 in the -D group, 8.7 +/- 0.64 in the N
      group, and 7.12 +/- 0.48 in the +D group (P < 0.05). The CD4(+)/CD8(+) ratio was
      2.23 +/- 0.15 in the -D group, 2.71 +/- 0.21 in the N group, and 2.73 +/- 0.31 in
      the +D group (P < 0.05). The plasma IFN-gamma levels were 416.42 +/- 16.42 pg/ml
      in the -D group, 325.41 +/- 11.16 pg/ml in the N group, and 276.26 +/- 25.32
      pg/ml in the +D group (P < 0.005). The plasma IL-10 levels were 16.45 +/- 1.58
      pg/ml in the -D group, 24.31 +/- 2.16 pg/ml in the N group, and 26.28 +/- 0.42
      pg/ml in the +D group (P < 0.005). The serum TB-PPD-specific antibody level was
      significantly higher in the -D group than in the N and +D groups. Vitamin D
      deficiency affects the immunity against Mycobacterium tuberculosis infection in
      mice. 

PMID- 22878934
TI  - Estimating the magnitude of food waste generated in South Africa.
AB  - Throughout the developed world, food is treated as a disposable commodity.
      Between a third and half of all food produced for human consumption globally is
      estimated to be wasted. However, attempts to quantify the actual magnitude of
      food wasted globally are constrained by limited data, particularly from
      developing countries. This article attempts to quantify total food waste
      generation (including both pre-consumer food losses, as well as post-consumer
      food waste) in South Africa. The estimates are based on available food supply
      data for South Africa and on estimates of average food waste generation at each
      step of the food supply chain for sub-Saharan Africa. The preliminary estimate of
      the magnitude of food waste generation in South Africa is in the order of 9.04
      million tonnes per annum. On a per capita basis, overall food waste in South
      Africa in 2007 is estimated at 177 kg/capita/annum and consumption waste at 7
      kg/capita/annum. However, these preliminary figures should be used with caution
      and are subject to verification through ongoing research.

PMID- 22878935
TI  - Enhanced solid waste stabilization in aerobic landfills using low aeration rates
      and high density compaction.
AB  - Historically, municipal solid waste landfills have been designed and operated as
      storage facilities with suboptimal degradation under anaerobic conditions
      resulting in slow waste stabilization, gaseous emissions and leachate formation.
      This article examines the aerobic bioreactor alternative combining the
      recirculation of high strength leachate [chemical oxygen demand (COD): 89,000
      95,600 mg/l; biological oxygen demand (BOD): 75,700-80,000 mg/l)] with low
      aeration rates (0.0125-0.05 l/min.kg) at high initial waste compaction (657-875
      kg/m3) to promote and control biodegradation of solid waste in laboratory-scale
      columns (diameter = 60 cm, height = 1 m). Low aeration rates coupled with high
      initial density demonstrated improved performance with increased levels of
      stabilization with COD and BOD attenuation reaching up to 96%, final C:N ratio of
      25 and waste settlement up to 55%.

PMID- 22878936
TI  - Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model.
AB  - Breast cancer stem cells, the root of tumor growth, present challenges to
      investigate: Primary human breast cancer cells are difficult to establish in
      culture and inconsistently yield tumors after transplantation into immune
      deficient recipient mice. Furthermore, there is limited characterization of
      mammary cancer stem cells in mice, the ideal model for the study of breast
      cancer. We herein describe a pre-clinical breast cancer stem cell model, based on
      the properties of cancer stem cells, derived from transgenic MMTV-PyMT mice.
      Using a defined set of cell surface markers to identify cancer stem cells by flow
      cytometry, at least four cell populations were recovered from primary mammary
      cancers. Only two of the four populations, one epithelial and one mesenchymal,
      were able to survive and proliferate in vitro. The epithelial population
      exhibited tumor initiation potential with as few as 10 cells injected into
      syngeneic immune-competent recipients. Tumors initiated from injected cell lines
      recapitulated the morphological and physiological components of the primary
      tumor. To highlight the stemness potential of the putative cancer stem cells, B
      lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) expression was knocked down
      via shRNA targeting Bmi-1. Without Bmi-1 expression, putative cancer stem cells
      could no longer initiate tumors, but tumor initiation was rescued with the
      introduction of a Bmi-1 overexpression vector in the Bmi-1 knockdown cells. In
      conclusion, our data show that primary mammary cancers from MMTV-PyMT mice
      contain putative cancer stem cells that survive in culture and can be used to
      create a model for study of mammary cancer stem cells.

PMID- 22878937
TI  - Glucagon-like peptide-1 and its cardiovascular effects.
AB  - Recently, the crucial role of GLP-1 in cardiovascular disease has been suggested
      by both preclinical and clinical studies. In vivo and in vitro studies have
      demonstrated cardio-protective effects of GLP-1 by activating cell survival
      signal pathways, which have greatly reduced ischemia/reperfusion injury and also
      cardiac dysfunction in various congestive heart failure animal models.
      Clinically, beneficial effects of GLP-1 have been shown in patients with
      myocardial infarction, hypertension, and heart failure, and 2 classes of incretin
      enhancers, GLP-1 receptor agonists and DPP-4 inhibitors, are currently available
      for the treatment of type 2 diabetes mellitus. In this review, we will summarize
      the role of incretins in various cardiovascular events such as hypertension and
      heart failure and postprandial lipoprotein secretion, and discuss their molecular
      mechanisms and potentials as a new therapeutic as well as preventive drug type
      for reducing cardiovascular events in both diabetic and nondiabetic patients.

PMID- 22878938
TI  - Parents' participation in a work-based anti-poverty program can enhance their
      children's future orientation: understanding pathways of influence.
AB  - Planning and preparing for life after high school is a central developmental task
      of American adolescents, and may be even more critical for low-income youth who
      are less likely to attend a four year college. This study investigates factors
      that led to the effects of the New Hope Project, a work-based, anti-poverty
      program directed at parents on youths' career-related thoughts and planning. The
      New Hope project was implemented in Milwaukee, WI, during the mid-1990s. 745
      families participated (52% male children; 56% African American; 30% Latino, and
      15% White non-Hispanic) and half were randomly selected to receive New Hope
      benefits, which included earnings supplements, job search assistance, and child
      and health care subsidies for 3 years. Importantly, effects on youths' future
      orientation were found 8 years after the program began (5 years after benefits
      ended). The present study investigates what factors sustained these positive
      impacts over time. Results indicate that parental perceptions of reading
      performance mediate the effects of New Hope on youths' cynicism about work.
      Additionally, parental perceptions of reading performance and youths' educational
      expectations mediate the effects of New Hope on boys' pessimism about future
      employment. These findings highlight the importance of youths' educational
      development to their career-related thoughts and planning.

PMID- 22878939
TI  - Prevalence of type 2 diabetes in Germany in 2040: estimates from an
      epidemiological model.
AB  - To estimate the number of persons in the age-group 55-74 years with type 2
      diabetes in Germany until 2040 and to analyze the impact of an intervention in a
      high risk group. A Markov model is used to generate forecasts by age and sex in
      each year using inputs of estimated diabetes prevalence, incidence and mortality
      based on actual national data. Projections about future demographics stem from
      the German Federal Office of Statistics. In a slightly modified model a state for
      persons with prediabetes is included to study the interplay of effect-size and
      participation quote on the number of persons with diabetes. The projected number
      of people with type 2 diabetes aged 55-74 years rises from 2.4 million in 2010 to
      3.9 million in 2030. From 2030 on this number will decrease slightly to 3.3
      million in 2040. If every second person aged 55-74 with prediabetes took part in
      a prevention program with the effect size of the Finnish Diabetes Prevention
      Program, 0.4 million cases could be prevented until 2030. To prevent 1.0 million
      cases in 2030, 90 % of all persons with prediabetes had to take part in an
      intervention that reduces the transition rate from prediabetes to diabetes by 55
      %. Unless enormous efforts are spent into prevention programs, the number of
      persons with type 2 diabetes will increase tremendously in the next two decades.

PMID- 22878940
TI  - Occurrence of lymphoplasmacytic lymphoma 6 years after amelioration of primary
      cold agglutinin disease by rituximab therapy.
AB  - Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia, classified
      into primary and secondary types. Secondary CAD accompanies infection or
      malignant disease, most often lymphoma, whereas primary CAD frequently represents
      a lymphoproliferative bone marrow disorder characterized by clonal expansion of B
      cells. Here, I describe a case of lymphoplasmacytic lymphoma (LPL) developed 6
      years after amelioration of primary CAD by rituximab monotherapy. A 54-year-old
      Japanese woman was diagnosed with primary CAD characterized by a small fraction
      of B lymphocytes and kappa laterality in the peripheral blood. M-protein was not
      detected by immuno-electrophoresis. The patient achieved remission following two
      courses of rituximab monotherapy. The level of IgM was specifically decreased,
      although levels of IgG and IgA were slightly increased. Six years after rituximab
      monotherapy, she developed LPL without CAD recurrence. Flow cytometry performed
      on bone marrow specimens revealed that lymphoma cells were positive for CD19 and
      CD20 with kappa laterality. The lymphoma may have transformed from clonal B
      lymphocytes at presentation of CAD. Rituximab monotherapy induced remission of
      CAD by specific decrease of IgM level, but did not eliminate the clonal B
      lymphocytes that may have progressed to LPL. This experience may provide clues
      toward the understanding of the pathophysiology of primary CAD with clonal
      lymphoproliferative disease of the bone marrow.

PMID- 22878942
TI  - [Diagnostic assessment of headache].

PMID- 22878941
TI  - Short- and long-term effects of rituximab for the treatment of thrombotic
      thrombocytopenic purpura: four case reports.
AB  - We report four cases of thrombotic thrombocytopenic purpura (TTP) successfully
      treated with rituximab in combination with plasma exchange and other
      immunosuppressive agents. All four cases fulfilled the diagnostic criteria of TTP
      with severe deficiencies in ADAMTS13 activity and a detectable anti-ADAMTS13
      inhibitor. Four weekly doses of 375 mg/m(2) rituximab were initiated on day 3-29
      of presentation as a salvage treatment for relapsing/refractory disease in three
      patients and as a first-line treatment in one. Resolution of clinical symptoms
      and hematological abnormalities occurred as early as the second dose and, after
      the completion of treatment, all four patients achieved complete response (CR).
      They are currently free from relapse and the duration of CR has been 13-72
      months. During the treatment course, the level of ADAMTS13 activity and the titer
      of the inhibitor correlated well with resolution or exacerbation of the disease.
      This report suggests that rituximab exhibits short- and long-term favorable
      effects for the treatment of TTP and that a severe ADAMTS13 deficiency and
      ADAMTS13 inhibitor positivity may support early administration of rituximab in
      both acute/refractory and relapsing cases.

PMID- 22878944
TI  - [Treating cocaine addiction].
AB  - Estimates assume approximately 100'000 occasional and 11'000 addicted cocaine
      consumers in Switzerland. Although there is no established "standard treatment",
      helpful pharmacological and psychotherapeutic treatment strategies for cocaine
      addiction and its consequences exist. A selection of the most relevant treatment
      options is presented in this review. Their application should be embedded within
      an individualized treatment plan, which usually includes several of the
      therapeutic elements presented hereafter, depending on the patient's current
      situation. The treatment of patients with cocaine dependence might encompass
      longer periods and multiple sequences of treatment in out- or inpatient setting,
      yet it is promising.

PMID- 22878945
TI  - [Osteoporotic fractures of axial skeleton].
AB  - Osteoporotic fractures most frequently first occur in the axial skeleton,
      especially in the vertebral bodies of the thoracolumbar transition. Beside pain,
      these fractures cause increasing kyphosis leading to changes in statics and a
      shift of the bodies' center of gravity. This results in physiological, functional
      as well as neurological consequences that cannot be managed by means of a
      conservative therapy. The purpose of this article is to provide a brief overview
      on diagnostics and therapy of such fractures. Furthermore, fractures of the pubic
      rami need to be mentioned. They pose another frequent location for osteoporotic
      fractures and are also associated with a high rate of morbidity and mortality.

PMID- 22878946
TI  - [Angiogenesis inhibitors and radiotherapy].
AB  - Tumor angiogenesis, i.e. the formation of new blood vessels, is a promising
      therapeutic target. Whereas angiogenesis inhibitors (AI) are selectively aimed
      against the tumors' vascular system, irradiation targets both, tumor cells and
      tumor vasculature. Biological interaction of both modalities has been shown on
      the level of tumor endothelial cells and the microenvironment. The clinical
      testing of this novel combined treatment strategy so far has been hindered,
      because AI intuitively increase tumor hypoxia and hypoxic tumors are radio
      resistant. However preclinical studies demonstrate that AI can even induce
      vascular normalization. Furthermore, consolidation therapy with AI after
      radiotherapy is a promising approach due to the specific biology of irradiated
      tumor bed. Based on these findings clinical studies are now increasingly been
      conducted.

PMID- 22878947
TI  - [Diagnostic assessment of asthma symptoms in primary care].

PMID- 22878948
TI  - [Bilaterale pneumonia after myocardial infarction].
AB  - A 63-year-old man was admitted with fever and bilateral pulmonary infiltrates
      accompanied by pleural effusion a few days after ST-segment elevation myocardial
      infarction treated with primary angioplasty and stent implantation. The diagnosis
      of early postmyocardial infarction syndrome (Dressler's syndrome) with pulmonary
      infiltrates was made after ruling out possible differential diagnosis such as
      pneumonia and congestive heart failure. Infiltrates and markers of inflammation
      resolved rapidly with systemic steroid therapy. Etiology, diagnosis and treatment
      of this immunological reaction with inflammation of pericardium, pleura and often
      pulmonary parenchyma are discussed.

PMID- 22878949
TI  - [Liver failure in a 27 years old female patient].
AB  - We report about a 27-years old female patient with acute liver failure due to an
      acute Budd Chiari Syndrom (thrombosis of all three liver veins an vena cava
      inferior) with caval web, birth control pills and after long distance flight.
      After successfull aspiration of the caval thrombus and dilatation of caval web
      liver transplantation could be bypassed. Two weeks after  intervention the
      patient was in a good healthy condition with normal laboratory values, normal
      liver size, normal perfusion of the V. cava inferior and signs of reperfusion of
      the middle liver vein.

PMID- 22878950
TI  - [Not Available].

PMID- 22878951
TI  - [Not Available].

PMID- 22878953
TI  - [CME - ECG 38. Arrhythmogenic right ventricular cardiomyopathy].

PMID- 22878956
TI  - Water- and nitrogen-dependent alterations in the inheritance mode of
      transpiration efficiency in winter wheat at the leaf and whole-plant level.
AB  - The effects of contrasting water and nitrogen (N) supply on the observed
      inheritance mode of transpiration efficiency (TE) at the flag-leaf and whole
      season levels were examined in winter wheat. Major components of the
      photosynthetic capacity of leaves and the season-integrated efficiency of water
      use in vegetative and grain mass formation were evaluated in parental lines of
      various origins and their diallel F(2)-hybrids grown in a factorial experiment
      under different moisture and N status of the soil. A broad genetic variation was
      mainly found for the season-long TE measures. The variation range in the leaf
      photosynthetic indices was usually narrow, but tended to slightly enhance under
      water and N shortage. Genotype-treatment interaction effects were significant for
      most characters. No consistency between the leaf- and season-long TE measures was
      observed. Preponderance of additivity-dependent variance was mainly identified
      for the season-integrated TE and leaf CO(2) assimilation rate. Soil treatments
      exhibited considerable influence on the phenotypic expression of gene action for
      the residual leaf measures. The contribution of non-additive gene effects and
      degree of dominance tended to increase in water- and N-limited plants, especially
      for the leaf transpiration rate and stomatal conductance. The results indicate
      that promise exists to improve the season-integrated TE. However, selection for
      TE components should be prolonged for later hybrid generations to eliminate the
      masking of non-additive causes. Such evaluation among families grown under sub
      optimal water and nitrogen supply seems to be the most promising strategy in
      winter wheat.

PMID- 22878957
TI  - Progression of prehypertension to hypertension in adolescents.
AB  - In the 2004 report from the National High Blood Pressure (BP) Education Program
      Working Group on BP in Children and Adolescents, the term "high normal BP" was
      replaced with the designation "prehypertension". It was proposed that BP levels
      that were higher than normal but did not reach the level of hypertension posed an
      increased risk for progression to hypertension. The overall intent of this
      description was to help identify children who were at the greatest risk for the
      development of hypertension. These are children and adolescents for whom targeted
      prevention programs are expected to be most beneficial. Following the 2004
      report, the prehypertension condition has been examined and described in
      adolescents as well as adults. This review summarizes the knowledge that has been
      gained on prehypertension including clinical characteristics, rates of
      progression to hypertension, and evidence of cardiovascular pathology.

PMID- 22878958
TI  - Randomized trial of pre-emptive or prophylactic valganciclovir therapy for
      prevention of cytomegalovirus infection in renal transplantation.

PMID- 22878959
TI  - Lifetime risk of ESRD: a meaningful concept?

PMID- 22878960
TI  - Absence of MyD88 signaling induces donor-specific kidney allograft tolerance.
AB  - Toll-like receptors (TLRs) play a fundamental role in innate immunity and provide
      a link between innate and adaptive responses to an allograft; however, whether
      the development of acute and chronic allograft rejection requires TLR signaling
      is unknown. Here, we studied TLR signaling in a fully MHC-mismatched, life
      sustaining murine model of kidney allograft rejection. Mice deficient in the TLR
      adaptor protein MyD88 developed donor antigen-specific tolerance, which protected
      them from both acute and chronic allograft rejection and increased their survival
      after transplantation compared with wild-type controls. Administration of an anti
      CD25 antibody to MyD88-deficient recipients depleted CD4(+)CD25(+)FoxP3(+) cells
      and broke tolerance. In addition, defective development of Th17 immune responses
      to alloantigen both in vitro and in vivo occurred, resulting in an increased
      ratio of Tregs to Th17 effectors. Thus, MyD88 deficiency was associated with an
      altered balance of Tregs over Th17 cells, promoting tolerance instead of
      rejection. This study provides evidence that targeting innate immunity may be a
      clinically relevant strategy to facilitate transplantation tolerance.

PMID- 22878961
TI  - Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism.
AB  - Renal Klotho controls mineral metabolism by directly modulating tubular
      reabsorption of phosphate and calcium and by acting as a co-receptor for the
      phosphaturic and vitamin D-regulating hormone fibroblast growth factor-23
      (FGF23). Klotho null mice have a markedly abnormal phenotype. We sought to
      determine effects of renal-specific and partial deletion of Klotho to facilitate
      investigation of its roles in health and disease. We generated a mouse model with
      partial deletion of Klotho in distal tubular segments (Ksp-KL(-/-)). In contrast
      to Klotho null mice, Ksp-KL(-/-) mice were fertile, had a normal gross phenotype,
      and did not have vascular or tubular calcification on renal histology. However,
      Ksp-KL(-/-) mice were hyperphosphatemic with elevated FGF23 levels and abundant
      expression of the sodium-phosphate cotransporter Npt2a at the brush border
      membrane. Serum calcium and 1,25-dihydroxyvitamin D(3) levels were normal but
      parathyroid hormone levels were decreased. TRPV5 protein was reduced with a
      parallel mild increase in urinary calcium excretion. Renal expression of vitamin
      D regulatory enzymes and vitamin D receptor was higher in Ksp-KL(-/-) mice than
      controls, suggesting increased turnover of vitamin D metabolites and a functional
      increase in vitamin D signaling. There was a threshold effect of residual renal
      Klotho expression on FGF23: deletion of >70% of Klotho resulted in FGF23 levels
      30-250 times higher than in wild-type mice. A subgroup of Ksp-KL(-/-) mice with
      normal phosphate levels had elevated FGF23, suggesting a Klotho-derived renal
      bone feedback loop. Taken together, renal FGF23-Klotho signaling, which is
      disrupted in CKD, is essential for homeostatic control of mineral metabolism.

PMID- 22878962
TI  - Angiotensin converting enzyme inhibitor-modulated microRNAs targeting renal
      fibrosis.

PMID- 22878963
TI  - Tracing the evolutionary history of the pandemic group A streptococcal M1T1
      clone.
AB  - The past 50 years has witnessed the emergence of new viral and bacterial
      pathogens with global effect on human health. The hyperinvasive group A
      Streptococcus (GAS) M1T1 clone, first detected in the mid-1980s in the United
      States, has since disseminated worldwide and remains a major cause of severe
      invasive human infections. Although much is understood regarding the capacity of
      this pathogen to cause disease, much less is known of the precise evolutionary
      events selecting for its emergence. We used high-throughput technologies to
      sequence a World Health Organization strain collection of serotype M1 GAS and
      reconstructed its phylogeny based on the analysis of core genome single
      nucleotide polymorphisms. We demonstrate that acquisition of a 36-kb genome
      segment from serotype M12 GAS and the bacteriophage-encoded DNase Sda1 led to
      increased virulence of the M1T1 precursor and occurred relatively early in the
      molecular evolutionary history of this strain. The more recent acquisition of the
      phage-encoded superantigen SpeA is likely to have provided selection advantage
      for the global dissemination of the M1T1 clone. This study provides an exemplar
      for the evolution and emergence of virulent clones from microbial populations
      existing commensally or causing only superficial infection.

PMID- 22878964
TI  - P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease,
      is associated with blood pressure.
AB  - BACKGROUND: Moyamoya disease-an idiopathic vascular disorder of intracranial
      arteries-is often accompanied by hypertension. RNF213 has been identified as a
      susceptibility gene for moyamoya disease. In the present study, the association
      of p.R4810K (G>A) with blood pressure (BP) was investigated in a Japanese
      population. METHODOLOGY/PRINCIPAL FINDINGS: Three independent study populations,
      the Nyukawa (n = 984), Noshiro (n = 2,443) and Field (n = 881) studies, joined
      this study. BP, body weight and height were measured. Past and present symptoms
      and disease and medication histories were assessed by interview. Associations of
      p.R4810K (rs112735431, ss179362673) of RNF213 with BP were investigated. Two
      linkage disequilibrium blocks were constructed for moyamoya patients with
      p.R4810K (n = 140) and the general population (n = 384) using 39 single
      nucleotide polymorphisms (SNPs) spanning 390 kb around RNF213. A total of 60
      carriers (3 for AA genotype and 57 for GA genotype) were found in these samples,
      and the minor allele frequencies were 1.4 % in the Nyukawa and Field studies and
      0.2 % in the Noshiro study. Regression analyses adjusted for age, sex and body
      mass index based on an additive model demonstrated significant associations with
      systolic BP (mmHg/allele): beta (standard error) was 8.2 (2.9) in the Nyukawa
      study (P = 4.7 * 10(-3)), 18.7 (5.4) in the Noshiro study (P = 4.6 * 10(-4)) and
      8.9 (2.0) (P = 1.0 * 10(-5)) in the three populations. In contrast, diastolic BP
      showed significant associations only in the Noshiro study. Linkage disequilibrium
      blocks contained none of the BP-associated proxy SNPs reported by previous
      studies. CONCLUSIONS/SIGNIFICANCE: Our study suggests that p.R4810K of RNF213 is
      associated strongly with systolic BP.

PMID- 22878965
TI  - Reading nonwords aloud: evidence for dynamic control in skilled readers.
AB  - In two experiments, we examined whether the dynamics of the reading system are
      adjusted on a trial-by-trial basis, despite the use of stimuli that all require
      the same spelling-sound translation routine. Subjects read aloud easy and more
      difficult nonwords in a predictable alternating sequence (AABB). Dynamic control
      was inferred via the observation of switch costs in response times and/or
      accuracy (A to B and B to A) for both types of items. Consistent with online
      control, switch costs were observed for both kinds of items. Various ways in
      which the reading system could adjust in response to such stimuli are considered.

PMID- 22878966
TI  - Tumor-infiltrating lymphocytes in melanoma.
AB  - Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the
      most effective treatment for patients with metastatic melanoma. With higher
      response rates than ipilimumab or IL-2, and longer durations of response than
      vemurafenib, TIL therapy carries the potential to transform current outcomes in
      melanoma, while also defining the way cell-based immunotherapy gets incorporated
      into mainstream cancer treatment. This paper will review the current state of TIL
      therapy in melanoma, the strategies to improve its efficacy, the current
      obstacles, and future directions to expand the availability of TIL to the general
      patient population.

PMID- 22878967
TI  - Cementless total hip arthroplasty in renal transplant patients.
AB  - We present our experience of contemporary cementless total hip arthroplasty (THA)
      conducted at a single institution to treat advanced avascular necrosis (AVN) in
      renal transplant patients. Between October 1997 and October 2008, 45 consecutive
      primary cementless THAs were performed in 30 patients with advanced AVN after
      renal transplantation. There were 18 males (27 hips) and 12 females (18 hips)
      (patient group) with an overall mean age 44 years (22 to 68). The clinical and
      radiographic results were compared with those of 96 sex and age-matched
      osteonecrotic hips in 72 patients that had not undergone organ transplantation or
      long-term steroid therapy (the control group). Patients were evaluated at surgery
      and at a mean of 7.2 years (2 to 13 years) postoperatively. The mean Harris hip
      score of patients improved from 48 points preoperatively to 94 points at last
      follow-up (p<0.05). Three hips in the patient group had massive osteolysis with
      polyethylene wear requiring revision surgery. One hip in the patient group
      underwent revision surgery because of recurrent dislocation at 11 years
      postoperatively. No intergroup differences in overall rates of complications or
      revisions were observed. However, transplant patients had a significantly higher
      rate of ectopic ossification. Despite diffuse osteopenia and chronic
      immunosuppression in renal transplant patients with osteonecrotic hips,
      cementless THA showed durable implant fixation to bone and no increased risk of
      complications.

PMID- 22878968
TI  - Hip flexion deformity improves without psoas-lengthening after surgical
      correction of fixed knee flexion deformity in spastic diplegia.
AB  - BACKGROUND: It is unclear if psoas lengthening surgery is required in the
      treatment of patients with cerebral palsy (CP) with hip flexion deformity and
      previous studies show equivocal results with regard to functional outcome.
      METHODS: This study retrospectively assessed 12 patients with a diagnosis of
      spastic diplegia who underwent single event multilevel surgery in order to
      correct deformities in the sagittal plane distal to the hip. Both clinical and
      instrument gait analysis results were recorded preoperatively, at one year (short
      term) and at five years (mid term) postoperatively. RESULTS: Clinically measured
      hip and knee movement improved at both short and mid term follow up. Correlations
      of clinically measured maximum hip and knee extension were significant at all
      three time points. Angles at terminal stance/toe off for hip and knee from
      kinematic data also showed significant correlations at all three time points.
      CONCLUSIONS: Our study demonstrates that the hip flexion deformities encountered
      in these patients will improve spontaneously when the distal fixed knee flexion
      deformity is surgically corrected. Therefore correction at the knee allows the
      ground reaction force to assume a more normal position resulting in correction at
      the hip over time. This then removes the need for surgery at the hip level. This
      fact is especially important when applied to psoas lengthening as this procedure
      can cause significant reduction in propulsion power.

PMID- 22878969
TI  - The hip antero-superior labral tear with avulsion of rectus femoris (HALTAR)
      lesion: does the SLAP equivalent in the hip exist?
AB  - BACKGROUND: The purpose of this report is to describe a new lesion, the "Hip
      Antero-superior Labral Tear with Avulsion of Rectus femoris (HALTAR)". This
      injury may be seen in both adolescent and skeletally mature athletes and shares
      several characteristics with the "Superior Labral tear from Anterior to Posterior
      (SLAP)" lesion in the shoulder. METHODS: We present a case example, as well as a
      detailed anatomic description of the pathological condition. RESULTS: As the
      rectus femoris crosses two joints it is exposed to substantial forces during
      muscle contraction. Considering the peri-articular origin of the reflected head
      at the superior aspect of the acetabular rim, a powerful eccentric contraction of
      the rectus femoris muscle or traction related to sudden knee flexion may cause an
      avulsion injury of the rectus femoris as well as a concomitant labral tear.
      CONCLUSIONS: A strain injury of the rectus femoris muscle, which is common in
      young athletic patients, may cause a concomitant tear of the acetabular labrum.
      Therefore, we recommend further diagnostic work-up in cases with prolonged hip
      pain and impaired hip function following an AIIS injury in order to identify any
      associated peri- and intra-articular damage. In our experience these patients
      seldom need aggressive surgical management.

PMID- 22878970
TI  - Survival of short hip stems with a "modern", trochanter-sparing design - a
      systematic literature review.
AB  - Modern total hip arthroplasty delivers excellent and reproducible results. New
      implant developments include a wide range of implants with a bone and tissue
      sparing design, including short femoral stems. This review was performed to
      provide an overview on the currently published survival results of short stems to
      allow comparison with the results of traditional hip stems. A literature search
      was performed to identify publications on short stems with a "modern" trochanter
      sparing design including implant survival information. Information was collected
      on the study population, follow-up time, implants used, implant survival and
      functional scores. The revision rate per 100 observed component years was
      calculated and compared to data presented in national arthroplasty registries.
      The methodological quality was assessed by employing a score specific to survival
      assessment of hip stems. In the course of 16 individual searches in EMBASE and
      Medline, 460 potentially eligible articles were identified. After thorough
      screening, 14 articles were deemed applicable. The variability in quality of the
      publications was high. No association between survival outcome and publication
      quality was apparent. The total revision rate over all studies was found to be
      0.38 per 100 component years with endpoint "stem revision for any reason". The
      survival rate of these stems is encouraging and appears to be comparable with
      that of more traditional uncemented stems. However, only few mid-term and long
      term studies are available. Reports with longer follow-up are needed to draw
      further conclusions.

PMID- 22878971
TI  - Surgical approach and patient-reported outcomes after total hip replacement.
AB  - BACKGROUND: Previous research has mainly focused on how factors such as surgical
      approach might affect implant survivorship and the incidence of complications.
      Given the increasing interest in patient-reported outcomes, the purpose of this
      study is to explore whether surgical approach is associated with patient-reported
      pain, function, and satisfaction at 1-3 years after primary total hip replacement
      (THR). METHODS: Details of surgical factors were collated from operation notes
      for all consecutive patients at our centre from 2004-2006. All patients were
      mailed a questionnaire 1-3 years following surgery that collected WOMAC pain and
      function scores and the Self-Administered Patient Satisfaction Scale for Primary
      Hip and Knee Arthroplasty. Of the eligible 1,315 patients, 911 patients returned
      a completed questionnaire (69% response rate). Multivariable fractional logit
      models were used to identify whether surgical approach was associated with
      outcome scores. RESULTS: Surgical approach was found to be a significant
      predictor of patient-reported outcomes at 1-3 years after surgery, even after
      controlling for patient-specific factors. A posterior approach was associated
      with better scores on all three outcome measures. On average, predicted outcome
      scores for a typical patient with a posterior approach were between 3.5 and 7.2
      percentage points higher than an equivalent patient with an anterolateral
      approach. INTERPRETATION: These findings suggest that clinical decisions
      concerning surgical approach may have an observable impact on patient-reported
      levels of pain, function, and satisfaction following THR.

PMID- 22878972
TI  - Cluster of three cases of invasive meningococcal disease in a preschool facility
      in West Bohemia, the Czech Republic.
AB  - From 1993 to 2009, there was only one cluster of invasive meningococcal disease
      (IMD) reported in a community of children in the Czech Republic. This exceptional
      cluster that occurred in a preschool facility is the focus of this report. In
      response to the announcement of the disease, anti-epidemic precautions were put
      in place. Neisseria meningitidis isolates were delivered from local laboratories
      to the National Reference Laboratory for Meningococcal Infections in Prague.
      Phenotyping was performed there along with multilocus sequence typing. Related
      factors and microbiological results were analyzed retrospectively. In October
      2009, three girls contracted IMD within a period of 1 week in a 42-member group
      in a preschool facility attached to the elementary school in Stary Plzenec
      Sedlec. In relation to three cases of the disease, another 66 people were
      registered of which 58 underwent a microbiological examination. N. meningitidis
      was detected in a total of five (8.6 %) people. The National Reference Laboratory
      for Meningococcal Infections defined the type of the strain to be C: P1.18-1,34
      2,38: F1-7: ST-467 (cc269) and penA27. Tests showed the precise identity of all
      strains obtained from the three sick children and of two strains contracted
      through contact with the preschool facility. Despite the complete recovery of all
      patients with no permanent damage, the need for rapid cooperation between
      clinical sites, diagnostic laboratories, and epidemiologists was confirmed.

PMID- 22878973
TI  - Neurological picture. Dispersion and 'salted pretzel sign' from thrombolysis of a
      spontaneous calcified embolus in an acute stroke.

PMID- 22878974
TI  - Cognitive behavior therapy for adults with attention-deficit/hyperactivity
      disorder: a review of recent randomized controlled trials.
AB  - To review the efficacy of cognitive behavioral therapy for adults with attention
      deficit hyperactivity disorder. Recent, controlled studies of the efficacy of
      Cognitive Behavior Therapy (CBT) treatment in adults with ADHD are reviewed. CBT
      is a feasible and acceptable treatment strategy in medicated adults with ADHD
      that leads to improvement in ADHD symptoms and co-morbid problems. CBT includes
      delivery of cognitive and/or emotional strategies to individuals or groups of 4
      to 10 participants. The number of CBT sessions may vary from 6 to 14. Blinding
      may help reduce response bias. Coaching and homework may enhance motivation as
      well as help in generalizing strategies to patient's daily lives. Outcomes
      studied include participants' self-reports of symptoms and evaluator reports
      based on standardized measures of ADHD and its comorbidities. CBT is an effective
      treatment for adults with ADHD particularly when combined with medication.

PMID- 22878975
TI  - Streptozotocin-induced insulin deficiency leads to development of behavioral
      deficits in rats.
AB  - Diabetes mellitus is one of the most common serious metabolic disorders in humans
      that develops due to diminished production of insulin (type I) or resistance to
      its effect (type II and gestational). The present study was designed to determine
      the neuropsychological deficits produced following streptozotocin-induced
      diabetes in rats. Rats were made diabetic by the intra-peritoneal administration
      of 60 mg/kg streptozotocin (STZ) which induces type-1 diabetes by the destruction
      "beta-cells" of pancreas. Body weight, food and water intake was monitored daily.
      Open field test (OFT) model, forced swim test (FST) and Morris water maze (MWM)
      model were performed for the evaluation of ambulation, depression-like symptoms
      and memory effects, respectively. After 10 days of diabetes induction the
      exploratory activity of rats was monitored by OFT while depression-like symptoms
      and memory effects in rats were analyzed by FST and MWM. Results showed that
      there was no significant effect of STZ-induced diabetes on body weight but food
      and water intake of STZ-induced diabetic rats was significantly increased.
      Exploratory activity was significantly decreased and short-term and long-term
      memory was significantly impaired while the depression-like symptoms was
      significantly increased in STZ diabetic rats. Thus, it may be suggested that STZ
      induced diabetes alters the brain functions and may play an important role in the
      pathophysiology of certain behavioral deficits like depression, impaired learning
      and memory functions related to diabetes. This finding may be of relevance in the
      pathophysiology and in the clinical picture, which could be related to an altered
      brain serotonin metabolism and neurotransmission and may possibly be related to
      neuropsychiatric disorders in diabetic patients.

PMID- 22878977
TI  - Population genetics of chronic kidney disease: the evolving story of APOL1.
AB  - Advances in human genome sequencing and generation of public databases of genomic
      diversity enable nephrologists to re-examine the genetics of common, complex
      kidney diseases. Non-diabetic kidney diseases prevalent in African ancestry
      populations and the allelic variation described in chromosome 22q12.3 is one such
      illustrative example. Newly available genomic database information enabled
      research groups to discover common functional DNA sequence risk variants in the
      APOL1 gene. These variants (termed G1 and G2) evolved to confer protection from a
      species of trypanosomal infection and thus achieved high prominence in many
      geographic regions of Africa and have been carried over to African diaspora
      communities worldwide. Since these discoveries two years ago, new insights have
      been gained: localization of APOL1 in normal and disease kidney tissues;
      influence of the APOL1 variants on the histopathology of HIV kidney disease;
      possible association with kidney transplant durability; onset of kidney failure
      at a younger age; association with blood lipid concentrations; more precise
      geographic localization of individuals with these variants to western and
      southern African ancestry; and the absence of the variants and kidney disease
      predisposition in Ethiopians. The definition of APOL1 nephropathy also confirms
      the long-held assumption by many clinicians that kidney disease attributed to
      hypertension in African populations represents an underlying glomerulopathy.
      Still awaited is the delineation of the biologic mechanisms of cellular injury
      related to these variants, to provide biologic proof of the APOL1 association and
      to provide potential targets for preventive and therapeutic intervention.

PMID- 22878976
TI  - The dynamic role of cardiac fibroblasts in development and disease.
AB  - Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they
      have been historically overlooked in terms of functional contributions to
      development and physiology, cardiac fibroblasts are now front and center. They
      are currently recognized as key protagonists during both normal development and
      cardiomyopathy disease, and work together with cardiomyocytes through paracrine,
      structural, and potentially electrical interactions. However, the lack of
      specific biomarkers and fibroblast heterogeneous nature currently convolutes the
      study of this dynamic cell lineage; though, efforts to advance marker analysis
      and lineage mapping technologies are ongoing. These tools will help elucidate the
      functional significance of fibroblast-cardiomyocyte interactions in vivo and
      delineate the dynamic nature of normal and pathological cardiac fibroblasts.
      Since therapeutic promise lies in understanding the interface between
      developmental biology and the postnatal injury response, future studies to
      understand the divergent roles played by cardiac fibroblasts both in utero and
      following cardiac insult are essential.

PMID- 22878978
TI  - Albumin upregulates eNOS mRNA through ETRA/B in human proximal tubular epithelial
      cells.
AB  - BACKGROUND: Proximal tubular cells respond to proteinuria by expressing several
      cytokines and inflammatory molecules that induce interstitial fibrosis. Increased
      attention has been drawn toward the systems of endothelin (ET) and nitric oxide
      (NO). This work contributes to the elucidation of the interplay between these two
      systems in proximal tubular epithelial cells (PTECs) after exposure in
      proteinuric conditions. METHODS: HK-2 cells, a human PTEC line, were incubated
      with albumin, simulating proteinuric conditions. Cells were then lysed and either
      total RNA was isolated or whole cell extracts were prepared. PreproET-1, ET
      receptors (ETRA and ETRB) and NO synthases (eNOS, iNOS) mRNA accumulation was
      estimated by RT-PCR, and proteins by Western blot analysis. NO production was
      assessed using Griess reaction. Furthermore, we treated HK-2 cells with NO donor
      sodium nitroprusside, NO inhibitor L-NAME, ETRA inhibitor BQ123, ETRB inhibitor
      BQ788 and purified ET-1, and investigated the potential interplay between albumin
      induced stimulation of NO or ET-1 systems. RESULTS: We found that albumin
      upregulates preproET-1, ETRA, ETRB, eNOS and iNOS mRNA as well as protein and
      stimulates NO production. Additionally, we recorded an ETRA/B dependent
      regulation of albumin-induced eNOS expression. CONCLUSIONS: For the first time an
      in vitro albumin-induced ET-1 and NO interplay was revealed.

PMID- 22878979
TI  - Diagnostic value of cystatin C and glomerular filtration rate formulae in Chinese
      nonelderly and elderly populations.
AB  - BACKGROUND: Serum cystatin C has been recognized as a surrogate marker for serum
      creatinine (SCr). However, whether cystatin C and cystatin C-based glomerular
      filtration rate (GFR) formulae offer any diagnostic value in nonelderly and
      elderly subjects has rarely been investigated. METHODS: Reference GFR (rGFR)
      values were established using the 99mTc-DTPA renal dynamic imaging method. Nine
      GFR formulae were used to predict estimated GFR (eGFR). RESULTS: A total of 534
      Chinese participants were enrolled. Cystatin C had a better diagnostic value than
      SCr. The superiority of cystatin C was more distinctly observed in the elderly.
      Combined cystatin C and SCr gave similar diagnostic values to cystatin C alone
      (p>0.05). Compared with single markers, GFR prediction formulae improved
      accuracy. Each formula had its own characteristics and applicability. Most
      formulae predicted with higher accuracy in the elderly than they did in the
      nonelderly. In chronic kidney disease (CKD) stage 1, the CKD-EPI formula had the
      least bias and the highest accuracy for the nonelderly, while the Hojs and Ma
      formulae performed best for the elderly. In the CKD stage 2-3, the Macisaac
      formula gave the most accurate eGFR. In the CKD stage 4-5, it was the CG formula
      that gave the closest estimate to the rGFR. CONCLUSIONS: Cystatin C could be
      superior to SCr, particularly in the elderly; however, cystatin C formulae and
      SCr formulae may possess their own applicability in different CKD stages and age
      groups. At present, it is not possible to say that cystatin C formulae are
      superior to SCr formulae.

PMID- 22878980
TI  - Further insights about the beneficial effects of n-3 fatty acids in the early
      molecular events of renal fibrosis in vitro.
AB  - BACKGROUND: Accumulating experimental and clinical evidence reveals beneficial
      effects of n-3 polyunsaturated fatty acids (PUFAs) in kidney disease by
      modulating inflammation and fibrosis mechanisms that lead to renal failure.
      METHODS: EPA, DHA (n-3 PUFAs) and AA (n-6 PUFA) effects, compared to those of
      AngII, on renal fibrotic processes at the extracellular matrix (ECM) level were
      verified in human mesangial cells in vitro, by means of RT-PCR, mitogenic assay
      and Western-blot analysis. RESULTS: Unlike AngII, EPA and DHA enhanced the
      expression of MMP2 and DN, a TGFbeta inhibitor, while decreasing mitogenic
      factors such as PDGF and bFGF, and cell proliferation. Moreover, n-3 PUFAs
      elicited Bax expression in AngII-treated cells and downregulated COX-2--an enzyme
      involved in the inflammatory cascade. The mechanism of action could implicate
      PPARgamma activation, as this transcription factor was shown to translocate to
      the nucleus upon n-3 PUFA treatment. CONCLUSIONS: These results complement our
      previous reports demonstrating that EPA and DHA prevent ECM accumulation and
      inflammation that typify the fibrotic process, providing new insights into the
      cellular and molecular mechanisms underlying their beneficial effects. We confirm
      that n-3 PUFAs could effectively counteract kidney fibrosis development providing
      a rationale for their use in clinical settings.

PMID- 22878981
TI  - Recurrent myelitis in common variable immunodeficiency successfully managed with
      high-dose subcutaneous immunoglobulin.
AB  - Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the
      spinal cord. We report on a 71-year-old woman with a recurrent cervical and
      thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis
      optica was ruled out such as other possible causes of acute and/or recurrent
      myelopathy. Serum immunoglobulin levels and specific antibody responses were
      consistent with the diagnosis of common variable immunodeficiency (CVID). She was
      treated with high-dose methylprednisolone and intravenous immunoglobulin. As a
      remission-maintaining drug, we decided to treat her with subcutaneous
      immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually
      employed in replacement therapy in CVID. At 3-year follow-up, the response to
      treatment was good. No relapses occurred. Our case suggests the effectiveness and
      safety of subcutaneous immunoglobulin in maintaining remission and in sparing
      prednisone in a woman with recurrent myelitis associated with CVID.

PMID- 22878982
TI  - Progressive neuropsychiatric and brain abnormalities after smoke inhalation.
AB  - A 46-year-old man inhaled combustible smoke of unknown chemical composition for
      15-20 min in an automobile body shop. Within 1&emsp14;month, he noted headache,
      sadness, anergia, anhedonia, agitation, poor sleep and impairment of
      concentration, attention and learning skills. Three years later, mental status
      examination showed major depression and cognitive disorder manifested by
      apprehension, continuous sadness, agitation, exhaustion, difficulty with word
      finding, bradyphrenia, short-term and long-term memory impairment, and judgement
      impaired by impulsive and affect-laden reactions without reflection. Impairments
      were noted on neuropsychiatric tests, and positron emission tomography (PET) scan
      of the brain with (18)F-fluorodeoxyglucose showed globally decreased and
      heterogeneous metabolic activity in the entire brain. Treatment included
      sertraline, methylphenidate, valproic acid and topiramate. At 14 years after
      smoke inhalation injury, he had persistent cognitive impairment. Repeat brain PET
      scan showed areas of improvement and deterioration. This case shows long-term
      brain and psychiatric dysfunction resulting after toxic smoke inhalation, with
      some areas of the brain having progressive deterioration between years 3 and 14
      after smoke inhalation.

PMID- 22878983
TI  - A 15-day-old male infant presenting with jerking movements of the limbs.
AB  - This 15-day-old Caucasian male infant presented to the clinic with his mother for
      a well-child visit. During the visit, the mother mentioned that she had observed
      jerking movements of the limbs, arms more than legs. Various tests were performed
      and observation in the ward helped determine the characteristics of the seizure
      like movements. The infant was born by vaginal delivery with vacuum extraction
      with a history of possible perinatal asphyxia. After seizures were observed in
      the ward, the patient was referred to neurology where an EEG was performed. It
      was normal, excluding epilepsy states. A normal newborn screen excluded most
      metabolic disorders. After history and examination, investigations and
      observation, benign sleep myoclonus was diagnosed. Benign sleep myoclonus is a
      benign disorder that consists of jerking movements of the limbs, usually
      involving the upper limbs more than the lower limbs and usually occurring during
      sleep. The seizures spontaneously stopped when the infant was approximately 1.5
      months old. This was consistent with the final diagnosis of neonatal sleep
      myoclonus.

PMID- 22878984
TI  - Pancreaticopleural fistula complicating chronic pancreatitis.
AB  - Pancreaticopleural fistula is an extremely rare complication of chronic
      pancreatitis with characteristic feature that it may appear in the absence of
      changes of acute pancreatitis. We present a case of a 32-year-old man whose CT
      scan showed multiple pseudocysts along the body and tail of the pancreas, left
      crus of diaphragm and in the posterior mediastinum with associated splenoportal
      thrombosis. MR cholangiopancreatography imaging diagnosed the case as a
      pancreatico-pleural fistula, with the fistulous tract connecting distal body and
      tail of the pancreas to the posterior mediastinum through a diaphragmatic hiatus
      with right-sided mild-to-moderate pleural effusion. Meanwhile the patient was
      treated conservatively for his acute symptoms that included pleural tap also.
      Finally, endoscopic retrograde cholangiopancreatography was done and minor
      papilla papillotomy was performed and a stent was placed. Knowledge about such
      cases would help one to be aware of such a rare but dangerous complication, so
      that timely and correct diagnosis and management can be undertaken.

PMID- 22878985
TI  - A rare presentation of cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is a rare skeletal dysplasia characterised by a
      defect in ossification. Frequently reported clinical findings are delayed closure
      of the fontanelles and cranial sutures, hypoplastic clavicles, dental
      abnormalities and short stature. Our patient suffered from complete absence of
      ossification of both parietal bones. This is a rare and severe defect that has
      been reported in only a few patients with CCD.

PMID- 22878986
TI  - Diffuse alveolar haemorrhage in granulomatosis with polyangitis (Wegener's) with
      coexistent rheumatoid arthritis.
AB  - Diffuse alveolar haemorrhage is a serious manifestation of granulomatosis with
      polyangitis (Wegener's) with high morbidity and mortality. It is defined by the
      clinical triad of haemoptysis, anaemia and progressive hypoxaemia. The diagnosis
      of granulomatosis with polyangitis is confirmed in an appropriate clinical
      setting by bronchoalveolar lavage, lung biopsy or detection of C-antineutrophil
      cytoplasmic antibodies. In this report, the patient was a known case of
      rheumatoid arthritis and presented with diffuse alveolar haemorrhage on CT scan;
      the underlying cause was found to be granulomatosis with polyangitis (Wegener's)
      with positive C-antineutrophil cytoplasmic antibodies. Despite aggressive
      treatment with immunosuppressants and steroids the patient died within a few
      days.

PMID- 22878987
TI  - An unusual presentation of pulmonary embolism.
AB  - Pulmonary embolism (PE) is a common cardiovascular emergency, by which occlusion
      of a part of the pulmonary arterial bed may lead to acute life threatening but
      potentially reversible right ventricular failure. Early diagnosis is fundamental
      to implement immediate effective treatment to reduce mortality. However, the
      diagnosis can be easily missed due to non-specific clinical presentation. We wish
      to present an unusual case whereby a patient with no risk factors for PE,
      symptoms suggestive of acute pericarditis and an ECG showing concave ST segment
      elevation was found to have multiple pulmonary emboli.

PMID- 22878988
TI  - Pneumatic retinopexy for treatment of posterior pole detachment following
      vitreoretinal surgery for diabetic tractional retinal detachment threatening the
      fovea.
AB  - To describe the usage of 100% perfluoropropane and subsequent laser retinopexy
      for the repair of posterior pole retinal detachment in a previously vitrectomised
      patient with diabetic tractional detachment.

PMID- 22878989
TI  - Presentation of opsoclonus myoclonus ataxia syndrome with glutamic acid
      decarboxylase antibodies.
AB  - In this rare case, the patient presented with opsoclonus, myoclonus and ataxia.
      Serological and imaging studies revealed high glutamic acid decarboxylase
      antibody (GAD-Ab) levels. High-dose corticosteroids were of no benefit and
      subsequent intravenous immunoglobulin (IVIg) administration proved resolution of
      the condition. Levetiracetam proved useful in symptomatically controlling the
      myoclonus. Follow-up GAD-Ab levels were within normal limits.

PMID- 22878990
TI  - An unusual mechanism of ocular trauma in badminton players: two incidental cases.
AB  - Badminton is a famous sport usually played without any protective eyewear. Ocular
      injury from one's own partner in a doubles game, with the shuttlecock, is rare.
      Two untrained badminton players presented with severe ocular trauma during a
      smash shot from the partner in a 'doubles' game. Both the players developed blind
      eye (vision <3/60) in spite of immediate treatment. This article describes an
      unusual mode of severe blunt trauma with a shuttlecock while playing a 'doubles'
      game, leading to coup-countercoup injury. In addition, the article highlights the
      need for awareness of the fatal ocular complications and life-long visual
      disability, especially in untrained badminton enthusiasts.

PMID- 22878991
TI  - Unsuspected pheochromocytoma of the urinary bladder: reminder of an important
      clinical lesson.
AB  - Bladder pheochromocytoma creates an extremely rare situation (0.06% of all
      bladder tumours). We came across a case with a complaint of intermittent episodes
      of haematuria. Cystoscopy revealed a solid, bluish submucosal growth with
      increased vascularity. Immediately after taking biopsy, the patient developed a
      sharp headache, chest heaviness and marked rise in blood pressure. The procedure
      was abandoned. Later, serum and urinary markers for pheochromocytoma were within
      normal limits. The histopathology report came out to be pheochromocytoma of the
      bladder. Later, partial cystectomy was carried out under general anaesthesia and
      histopathology confirmed the same. Thus, a surgeon/urologist should have a high
      index of suspicion for bladder pheochromocytoma while dealing with such cases if
      he comes across the characteristic symptoms of sharp headache, hypertension,
      palpitation, sweating, fainting or blurring of vision immediately after voiding
      or during the cystoscopic manipulation of tumour or cystoscopic findings of a
      submucosal supratrigonal vascular tumour with a bluish hue.

PMID- 22878992
TI  - Necrotising fasciitis of the thumb.
AB  - Necrotising fasciitis is a rare condition that should be diagnosed early and
      managed aggressively in order to avoid death. We present a case of necrotising
      fasciitis of the thumb and discuss the assessment and management of this serious
      condition. A 44-year-old woman presented with a painful and erythematous right
      thumb and progressive swelling of her hand following a minor injury to the tip of
      her thumb 3 days previously. A diagnosis of necrotising fasciitis was made and
      the patient underwent urgent debridement of non-viable tissue. She required 1
      week of supportive therapy in intensive treatment unit and was discharged from
      hospital after 3 weeks. Necrotising fasciitis is a rapidly progressing life
      threatening infection, usually caused by streptococcal organisms. Immediate
      resuscitation, broad-spectrum intravenous antibiotics and early surgical
      debridement are necessary in order to avoid significant morbidity and mortality.

PMID- 22878993
TI  - Cervical ectopics: less can be more.
AB  - A 27-year-old woman with a positive urinary-pregnancy test, complaining of slight
      vaginal bleeding and some diffuse lower abdominal pain, presented to the
      emergency gynaecology unit at the Royal Free Hospital. Her initial ultrasound
      scan was inconclusive, and so serial serum beta human chorionic gonadotropin
      (hCG) blood tests were carried out. These demonstrated a suboptimal increase. A
      second transvaginal ultrasound (TVUS) was therefore performed, which showed a
      live cervical ectopic pregnancy. The patient, who remained haemodynamically
      stable, was admitted. She was treated with intramuscular methotrexate. She was
      given a second dose of methotrexate after 1&emsp14;week, since her beta hCG
      levels did not demonstrate a satisfactory fall. A rapid decrease in serum hCG was
      then observed and the patient was then discharged. An outpatient TVUS was normal.
      The patient remained well throughout her treatment, never suffered any profuse
      vaginal bleeding, and thus surgical intervention was avoided.

PMID- 22878994
TI  - Tuberous sclerosis complex presenting as bilateral large renal angiomyolipomas.
AB  - Tuberous sclerosis is an inherited disorder that can present with seizures,
      mental retardation, cutaneous lesions and visceral hamartomas, but can be
      entirely asymptomatic. The disease occurs in 1:100 000 persons in all races with
      nearly equal distribution between the sexes. Tuberous sclerosis is often
      associated with renal angiomyolipomas (AMLs), which occur in up to 80% of these
      patients. Here we report a case of a patient who presented with bilateral large
      renal AMLs and was detected to have tuberous sclerosis complex.

PMID- 22878995
TI  - Ban Tu Wan hepatotoxicity.
AB  - Medications are thought to contribute to approximately 50% of the cases of acute
      liver failure in the USA. This number includes some herbal medications and
      supplements. However, little regulatory oversight of these later substances
      occurs. This report describes a case of fulminant hepatic failure secondary to
      Ban Tu Wan (a Chinese herb). We discuss the use of this herbal supplement and the
      relationship to drug-induced hepatitis.

PMID- 22878996
TI  - Spinal extradural cavernous haemangioma in an elderly man.
AB  - Cavernous haemangiomas are vascular malformations that may affect any part of the
      central nervous system. Epidural haemangiomas are rare and constitute ~4% of all
      epidural tumours and 12% of all intraspinal haemangiomas. These tumours enlarge
      slowly and produce symptoms of progressive myelopathy or radiculopathy or both.
      History, clinical examination, routine radiographs, MRI and histopathological
      studies are the aids for a definitive diagnosis. Surgery can give a very
      beneficial result with good functional and neurological improvement. Chance of
      recurrence is less after a good surgical removal. Here we present a case of
      spinal extradural cavernous haemangioma in a 65- year-old man who had a good
      functional and neurological recovery after surgery. At 9 months postoperative
      follow-up, he did well without any new problems with regard to recurrence. We
      report this case for its rarity.

PMID- 22878997
TI  - Toxic megacolon from fulminant Clostridium difficile infection induced by topical
      silver sulphadiazine.
AB  - Pseudomembranous colitis and toxic megacolon (TM) are well-known complications of
      Clostridium difficile infections. Systemic antibiotic is considered as the major
      risk factor for the development of C difficile colitis. However, topical
      antibiotics are rarely associated with the infection. As previously thought, the
      use of topical antibiotic is capable of systemic absorption in damaged and
      denuded skin; sufficient enough to suppress the normal bowel flora. Here, we
      present an unusual case of TM from C difficile infection induced by topical
      silver sulphadiazine in a 60-year-old man with immune-bullous pemphigus vulgaris.
      The diagnosis is further complicated by the absence of diarrhoea as the initial
      presentation. Despite adequate medical and surgical intervention, the patient had
      an unfavourable outcome.

PMID- 22878998
TI  - Acute onset of generalised pruritus as presenting symptom of Klatskin tumour.
AB  - A 60-year-old Korean woman presented with generalised pruritus and abdominal
      pain. She was initially treated with oral antihistamine therapy, but upon
      progression of symptoms and jaundice involvement, she was found to have a
      Klatskin tumour. The patient was not a candidate for surgical resection and is
      currently undergoing palliative care.

PMID- 22878999
TI  - Sensory neuropathy in paraneoplastic leucocytosis.
AB  - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) sensitise nerves to mechanical stimuli experimentally
      and may induce bone and muscle pain when used as supportive drugs. G-CSF and GM
      CSF produced endogenously by tumour cells can cause paraneoplastic leucocytosis.
      Whether paraneoplastic leucocytosis is associated with changes in pain
      sensitivity is not yet clear. We report on a patient with advanced-stage thyroid
      cancer who developed extreme leucocytosis within a period of 4 weeks (103 000
      white blood cells/mm(3)), composed mostly of neutrophils and eosinophils.
      Parallel to this leukemoid reaction, allodynia and hyperalgesia developed in the
      absence of tissue inflammation. The course of disease of an elderly male with
      advanced stage metastatic thyroid cancer with new onset neuropathic pain followed
      by the development of extreme leucocytosis in a leukemoid reaction suggests
      paraneoplastic release of myeloid CSFs. The coincidence of pain sensitisation and
      extreme leucocytosis suggests a causal contribution of G-CSF and GM-CSF.

PMID- 22879000
TI  - Diagnostic dilemmas in cardiology.
AB  - A 29-year-old pregnant woman presented in accident and emergency with severe
      acute left ventricular failure requiring admission to the intensive care unit. A
      nasal swab was found to be positive for H1N1 making peripartum and viral
      cardiomyopathies, the most likely differential diagnoses. CT coronary angiography
      and subsequent invasive angiography revealed an anomalous coronary system thus
      making ischaemic cardiomyopathy also a possibility. Cardiac MRI played a vital
      role in identifying the underlying cause, which in this case was that of H1N1
      influenza cardiomyopathy. Correct diagnosis in such patients is paramount as this
      impinges on patients' overall prognosis. In this case aggressive initial therapy
      including inotropic support and invasive ventilation followed by standard
      antifailure treatment with beta-blockers and angiotensin-converting enzyme
      inhibitors led to restoration of the patient's left ventricular function and an
      associated marked improvement in symptoms.

PMID- 22879001
TI  - Bilateral pneumothoraces and pulmonary oedema following tracheostomy induced by
      acute tracheal obstruction.
AB  - We describe the presentation of bilateral pneumothoraces with pulmonary oedema
      following an elective tracheostomy. A 69-year-old man underwent panendoscopy
      following primary chemoradiotherapy for locally invasive vocal cord carcinoma. A
      tracheostomy was performed for upper airway oedema and necrosis. Postoperatively,
      acute airway obstruction with profound desaturation developed. Tracheostomy tube
      suctioning dislodged an airway clot with clinical improvement and restoration of
      bilateral breath sounds. A chest X-ray subsequently demonstrated bilateral
      pneumothoraces with marked pulmonary oedema. Management, including chest drain
      insertion, resulted in stabilisation and subsequent full recovery. This case
      highlights the potential for more than one cause of life-threatening complication
      following tracheostomy. The importance of considering multiple pathologies in the
      setting of severe hypoxia and to institute prompt management is emphasised.

PMID- 22879002
TI  - The hairy-print for levamisole-induced vasculitis.
AB  - Levamisole-induced vasculitis is a well-characterised antineutrophil cytoplasm
      antibodies (ANCA)-positive vasculitis in cocaine abuser patients. However, due to
      the short half-life of levamisole in serum and urine, the causal role of
      levamisole is not established. Here we report the detection of both levamisole
      and cocaine in hair samples of a patient who presented with an ANCA-positive
      vasculitis. The higher concentration of levamisole in proximal sample of the hair
      confirms that the patient abused of cocaine added with levamisole in the days
      preceding the development of skin lesions. Although a direct causative role has
      not been established, our report strongly suggests that levamisole may have
      triggered vasculitis in this case.

PMID- 22879003
TI  - Vacant mitochondria in the myocardium of a patient with mitochondrial
      cardiomyopathy and diabetes mellitus.

PMID- 22879004
TI  - Elevated cerebrospinal fluid tau in Wernicke encephalopathy.
AB  - Wernicke encephalopathy (WE) commonly presents with oculomotor abnormalities,
      gait ataxia and confusion. WE can mimic rapidly progressive dementia syndromes,
      such as Creutzfeldt-Jakob disease (CJD). Cerebrospinal fluid (CSF) tau is
      frequently used for diagnosis of several dementia subtypes, predominantly CJD and
      Alzheimer's disease. The combination of very high CSF tau (tau) and normal
      phosphorylated tau (p-tau) levels is almost exclusively seen in aggressive
      diseases, such as CJD. The authors present a case of a woman with WE, caused by
      chronic insufficient dietary intake, with highly elevated CSF tau and normal p
      tau. The clinical symptoms and CSF findings raised the suspicion of CJD. However,
      shortly after immediate treatment with thiamine the patient clinically improved.
      At follow-up, 2.5&emsp14;months later, she had made a good recovery. This case of
      rapidly progressive dementia illustrates that, even in the case of a highly
      elevated CSF tau, clinicians should be alert for treatable causes such as WE.

PMID- 22879005
TI  - An unusual cause of a pulmonary opacity in a visitor to the UK.
AB  - A 64-year-old man, resident in Arizona for 3&emsp14;years, presented with a week
      long history of a dry cough and 'flu-like symptoms'. He had recently been
      renovating his house. A chest radiograph showed a left mid-zone opacity.
      Investigations for lung cancer were performed and he underwent CT-guided biopsy
      of the lesion. A coccidioidal fungus known to cause 'Valley Fever' was isolated.
      Treatment with fluconazole led to a complete recovery. This fungal infection is
      endemic in parts of the USA and Mexico and usually presents with respiratory
      symptoms. Additional complications include disseminated disease and meningitis.

PMID- 22879006
TI  - Right heart failure caused by metastatic renal cell carcinoma masquerading as an
      obstructive cardiac tumour.

PMID- 22879007
TI  - Effects of experimentally deviated mandibular position on stress response.
AB  - The purpose of this study was to investigate the effects of stress on -prefrontal
      cortex (PFC), emotion (using visual analogue scale, VAS, and State-Trait Anxiety
      Inventory, STAI), and the autonomic nervous system (ANS). Two types of stress
      were applied: (1) malocclusion-induced physical stress and (2) mental stress
      induced by an arithmetic task. Malocclusion was induced using an experimentally
      deviated mandibular device (EDMD) to obtain an experimentally deviated mandibular
      position (EDMP). A total of 11 healthy volunteers participated in the study. On
      day 1 they performed a pretrial arithmetic task followed by a 10-min rest, after
      which they performed a posttrial EDMD + arithmetic task or rest device +
      arithmetic task. These two tasks were selected at random and assigned at the rate
      of one per day. Activity in the PFC tended to show an increase in the pretrial
      arithmetic tasks and rest device + arithmetic task, but a decrease in the EDMD +
      arithmetic task compared with the rest device + arithmetic task. Heart rate
      significantly increased during the rest device + arithmetic task, whereas no
      significant difference was observed during the EDMD + arithmetic task. The EDMD +
      arithmetic task significantly increased STAI scores (p = 0.0047), and the
      significant decrease in VAS indicated "unpleasant" (p = 0.035). These findings
      suggest that EDMP-induced reduction in the level of PFC activity was a response
      to discomfort, indicating that EDMP affects systemic function such as that of the
      ANS as an unpleasant stressor.

PMID- 22879008
TI  - Kidney EPO expression during chronic hypoxia in aged mice.
AB  - In order to maintain normal cellular function, mammalian tissue oxygen
      concentrations must be tightly regulated within a narrow physiological range. The
      hormone erythropoietin (EPO) is essential for maintenance of tissue oxygen supply
      by stimulating red blood cell production and promoting their survival. In this
      study we compared the effects of 290 Torr atmospheric pressure on the kidney EPO
      protein levels in young (4-month-old) and aged (24-month-old) C57BL/6 mice. The
      mice were sacrificed after being anesthetized, and kidney samples were collected
      and processed by Western blot analysis. Relatively low basal expression of EPO
      during normoxia in young mice showed significant upregulation in hypoxia and
      stayed upregulated throughout the hypoxic period (threefold compared to normoxic
      control), showing a slight decline toward the third week. Whereas, a relatively
      higher normoxic basal EPO protein level in aged mice did not show significant
      increase until seventh day of hypoxia, but showed significant upregulation in
      prolonged hypoxia. Hence, we confirmed that there is a progressively increased
      accumulation of EPO during chronic hypoxia in young and aged mouse kidney, and
      the EPO upregulation during hypoxia showed a similarity with the pattern of
      increase in hematocrit, which we have reported previously.

PMID- 22879009
TI  - Nature's "silver bullet" for anticoagulation: mechanism of Zymogen Protein C to
      Activated Protein C.
AB  - We have defined the Zymogen Protein C (ZPC) to Activated Protein C (APC) process
      as the "silver bullet" of blood anticoagulation. This definition suggests that
      the anticoagulation activity occurs when and where it is needed, resulting in
      local anticoagulation without enhanced bleeding. It is important for man to be
      able to manufacture an inexpensive ZPC product or to find a substitute drug to
      duplicate one of God's natural anticoagulant/antithrombotic processes, in vivo,
      in human blood. After intense research and at great expense scientists have not
      been able to produce a safe anticoagulant. All products that are now being used
      can cause bleeding even if dosing is carefully monitored. In fact many
      professionals in the health care and the pharmaceutical industries define an
      anticoagulant as a drug that "does" cause bleeding. This results in a large
      financial burden that has been placed on the health care industry because of
      necessary emergency treatments for dangerous occurrences. In addition, many
      patients are dying annually due to internal and external bleeds created or
      enhanced by presently administered anticoagulants. Since there are no safe drugs
      available it is necessary to use the existing products when a medical condition
      calls for an anticoagulant. This paper will discuss the ZPC process and why its
      mechanistic design is one of nature's unique defenses against unwanted blood
      clotting. The prevention and lysis of clots allows normal blood flow and
      therefore results in the required tissue oxygenation for cell function and
      survival. If clinical research is carried out with great care it could uncover
      other uses of ZPC that will allow safer medical procedures, in addition to its
      use with standard PC deficiency cases. An important example might be for some
      brain surgeries where the use of existing anticoagulants is unsafe because of
      potential bleeds. Clinical research could reveal an efficacious ZPC level (for
      instance, 125, 150, or 200% of normal) that would prevent dangerous clotting
      situations from occurring without unnecessary bleeding.

PMID- 22879010
TI  - Canonical correlation analysis in the study of cerebral and peripheral
      haemodynamics interrelations with systemic variables in neonates supported on
      ECMO.
AB  - Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk
      of brain injury due to haemodynamic instability. In order to monitor cerebral and
      peripheral (muscle) haemodynamic and oxygenation changes in this population we
      used a dual-channel near-infrared spectroscopy (NIRS) system. In addition, to
      assess interrelations between NIRS and systemic variables, collected
      simultaneously, canonical correlation analysis (CCA) was employed. CCA can
      quantify the relationship between a set of variables and assess levels of
      dependency. In four out of five patients, systemic variables were found to be
      less inter-related with cerebral rather than peripheral NIRS measurements.
      Moreover, during ECMO flow manipulations, we found that the interrelation between
      the systemic and the NIRS cerebral/peripheral variables changed. The CCA method
      presented here can be used to assess differences between NIRS cerebral and NIRS
      peripheral responses due to systemic variations which may be indicative of
      physiological differences in the mechanisms that regulate oxygenation and/or
      haemodynamics of the brain and the muscle.

PMID- 22879011
TI  - Blood oxygen level dependent magnetization transfer (BOLDMT) effect.
AB  - A few studies have reported that magnetization transfer (MT) -preparation
      interacts with blood oxygen level dependent (BOLD) contrast used for functional
      magnetic resonance imaging (MRI). However, the mechanism is still not well
      established. This study shows that blood oxygenation level itself affects MT
      contrast. MT ratio (MTR) decreases with increased blood oxygenation, which is
      demonstrated by ex vivo and in vivo experiments. Oxygenated blood shows less MTR
      contrast compared to deoxygenated blood sample; and higher levels of oxygen
      inhalation decrease tissue MTR in vivo especially in brain tumor region. The
      percentage reduction of MTR due to hyperoxia inhalation, referred to as the blood
      oxygen dependent magnetization transfer (BOLDMT) effect, correlates well with
      tissue oxygen extraction, which is highest in well-vascularized tumor rim,
      followed by inner tumor, gray matter (GM), and white matter (WM) normal tissue.
      Simulations and experiments demonstrate that BOLDMT effect induced with hyperoxia
      inhalation may be generated by decreased tissue T (1) due to increased O(2)
      dissolution and increased tissue T (2) due to reduced deoxyhemoglobin (dHb)
      concentration. Compared to regular T (2)* weighted BOLD contrast, BOLDMT has
      higher insensitivity to B (0) inhomogeneities. BOLDMT may potentially serve as a
      reliable and novel biomarker for tumor oxygen extraction.

PMID- 22879012
TI  - Characterizing prostate tumor mouse xenografts with CEST and MT-MRI and redox
      scanning.
AB  - The main goal of this study was to use multimodality imaging methods to reveal
      the heterogeneity in prostate cancer and seek the correlation between the
      characteristic heterogeneity and tumor aggressiveness. Here we report the
      preliminary data on chemical exchange saturation transfer (CEST) and
      magnetization transfer (MT) magnetic resonance imaging (MRI) and redox scanning
      [cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized
      flavoproteins) fluorescence imaging] of two aggressive human prostate tumor lines
      (DU-145 and PC-3) xenografted in athymic nude mice. The results obtained by these
      methods appeared to be consistent, with all showing a higher level of
      heterogeneity in DU-145 tumors than in PC-3 tumors. DU-145 tumors showed CEST
      maps with both positive and negative areas while PC-3 CEST maps were relatively
      homogeneous. The mean CEST value for PC-3, 23.0 +/- 2.1 %, is at a significantly
      higher level (p < 0.05) than DU-145 (1.9 +/- 6.7 %) at the peak of the CEST
      asymmetric curve (+2 ppm). Fp redox ratio (Fp/(NADH + Fp)) images exhibited
      localized highly oxidized regions in DU-145 tumors, whereas PC-3 tumors appeared
      to be less heterogeneous. These results suggest a possible role of metabolism in
      tumor progression. More studies, including an indolent prostate tumor line and
      with larger sample size, will be performed in the future to identify the
      biomarkers for prostate tumor aggressiveness.

PMID- 22879013
TI  - In vitro Sirius Red collagen assay measures the pattern shift from soluble to
      deposited collagen.
AB  - In this study, we compared two in vitro collagen production assays ([(3)H]
      proline incorporation and Sirius Red) for their ability to determine the pattern
      shift from soluble to deposited collagen. The effect of the antifibrotic agent,
      triptolide (TPL), on collagen production was also studied. The results showed
      that: (1) 48 h after NIH 3T3 (murine embryo fibroblast) and HFL-1(human fetal
      lung fibroblast) were exposed to transforming growth factor-beta 1 (TGF-beta),
      there was an increase in soluble collagen in the culture medium; (2) on day 4,
      soluble collagen declined, whereas deposited collagen increased; (3) Sirius Red
      was easier to use than [(3)H]-proline incorporation and more consistently
      reflected the collagen pattern shift from soluble to deposited; (4) the in vitro
      Sirius Red assay took less time than the in vivo assay to determine the effect of
      TPL. Our results suggest that: (a) the newly synthesized soluble collagen can
      sensitively evaluate an agent's capacity for collagen production and (b) Sirius
      Red is more useful than [(3)H]-proline because it is easier to use, more
      convenient, less time consuming, and does not require radioactive material.

PMID- 22879014
TI  - Intravoxel incoherent motion MR imaging of the kidney: pilot study.
AB  - MR examinations (Achieva 3 T, Philips, Best, The Netherlands) were performed at
      five different occasions in a healthy volunteer (male 60 years) and in one renal
      cancer patient (male 78 years) with normal renal function (creatinine 88
      MUmol/L). Intravoxel incoherent motion (IVIM) coefficients D + D* were measured
      using respiratory-triggered diffusion-weighted spin-echo echo-planar imaging.
      Perfusion data of the patient were acquired using a saturation-recovery gradient
      echo sequence and with the bolus of Gd-BOPTA (Multihance). D + D* were computed
      by monoexponential fitting of MR signal intensity attenuation versus b for b = 0,
      50, 100, 150 s/mm(2). Perfusion parameters were evaluated with "NordicICE"
      software. The map of D + D* was compared qualitatively with the perfusion map
      computed from the Gd scan. D + D* values of the cortex and medulla were in the
      range 2.3-2.7 and 1.1-1.6 * 10(-3) mm(2)/s, respectively. In conclusion, in this
      pilot study a good qualitative relation between IVIM variables D + D* and renal
      perfusion has been found.

PMID- 22879015
TI  - Changes in gastric mucosa, submucosa, and muscularis IC pH may herald
      irreversible tissue injury.
AB  - Previously we noted an abrupt rise in gastric intracellular pH (IC pH) and
      bicarbonate buffering between 15 and 30 min of cardiac arrest which we termed
      agonal alkalinization, failure of pH regulation. Agonal alkalinization may
      represent the transition point between reversible and irreversible injury. We
      asked the question, what is the sequence of change in IC pH within the gastric
      layers, mucosa, submucosa, and muscularis, and which layer is most sensitive?
      This research explored changes in IC pH within the stomach layers, mucosa,
      submucosa, and muscularis, at 0, 5, 15, 30, and 40 min, under three conditions,
      normoxia (control), ischemia (cardiac arrest), and eucapnic hypoxia (12 %
      oxygen). The mucosa was the most alkalotic gastric layer at baseline. Ischemia
      and hypoxia at 40" produced different layer responses with the mucosa and
      submucosa the most sensitive layers during ischemia and the muscularis during
      hypoxia. Further study to examine the mechanism of changes between gastric layers
      using spatial-temporal techniques may assist in understanding the transition to
      irreversible injury.

PMID- 22879016
TI  - Normobaric hyperoxia does not change optical scattering or pathlength but does
      increase oxidised cytochrome C oxidase concentration in patients with brain
      injury.
AB  - We report the use of a novel hybrid near-infrared spectrometer for the
      measurement of optical scattering, pathlength and chromophore concentration in
      critically ill patients with brain injury. Ten mechanically ventilated patients
      with acute brain injury were studied. In addition to standard neurointensive care
      monitoring, middle cerebral artery flow velocity, brain lactate-pyruvate ratio
      (LPR) and brain tissue oxygen tension were monitored. The patients were subjected
      to graded normobaric hyperoxia (NBH), with the inspired fraction of oxygen
      increased from baseline to 60% then 100%. NBH induced significant changes in the
      concentrations of oxyhaemoglobin, deoxyhaemoglobin and oxidised-reduced
      cytochrome c oxidase; these were accompanied by a corresponding reduction in
      brain LPR and increase in brain tissue oxygen tension. No significant change in
      optical scattering or pathlength was observed. These results suggest that the
      measurement of chromophore concentration in the injured brain is not confounded
      by changes in optical scattering or pathlength and that NBH induces an increase
      in cerebral aerobic metabolism.

PMID- 22879017
TI  - Multi-frequency forced oscillation technique using impulse oscillations: can it
      give mechanical information about the lung periphery?
AB  - Forced oscillation techniques (FOTs) using sine curved oscillatory waves are used
      for assessing the lung periphery, but measure only overall respiratory mechanics.
      Therefore, mathematical models of the respiratory system serve as vehicles to
      obtain detailed mechanics. Although the simplest model of respiratory mechanics
      is a simple 3-element series (RIC) model, the constant phase (CP) model is
      recently used for characterizing respiratory mechanics, which has the advantage
      of partitioning of respiratory mechanics into airway and tissue components.
      Meanwhile, FOTs using non-sine curved oscillatory waves are easily applied in
      patients with severe respiratory diseases because they do not require voluntary
      apnea. If the latter type of FOTs is as informative as the former, the question
      arises whether a FOT using non-sine curved oscillatory waves (IOS) could be used
      to study mechanical properties of the lung periphery. And the CP model should fit
      the impedance spectra. To answer this, subjects with lymphangioleiomyomatosis
      (LAM) were recruited as a cohort of patients with lung parenchymal disease.
      Impedance spectra obtained by the IOS were fitted to the CP and RIC models. Mean
      values of goodness of fit from the CP and RIC models were 0.978 +/- 0.022 and
      0.968 +/- 0.026, respectively. The extra sum-of-squares F test was used to
      compare the two mathematical models. The F ratio was 2.37 +/- 1.40 and the p
      value was 0.29 +/- 0.21. Unfortunately, there was no compelling evidence for
      adopting the CP model for the evaluation of impedance spectra obtained by IOS.
      This result might relate to the uncertainty of IOS for detecting mechanical
      properties of the lung periphery.

PMID- 22879018
TI  - NIRS measurements with elite speed skaters: comparison between the ice rink and
      the laboratory.
AB  - Wearable, wireless near-infrared (NIR) spectrometers were used to compare changes
      in on-ice short-track skating race simulations over 1,500 m with a 3-min cycle
      ergometry test at constant power output (400 W). The subjects were six male elite
      short-track speed skaters. Both protocols elicited a rapid desaturation (?TSI%)
      in the muscle during early stages (initial 20 s); however, asymmetry between
      right and left legs was seen in DeltaTSI% for the skating protocol, but not for
      cycling. Individual differences between skaters were present in both protocols.
      Notably, one individual who showed a relatively small TSI% change (-10.7%, group
      mean = -26.1%) showed a similarly small change during the cycling protocol (
      5.8%, group mean = -14.3%). We conclude that NIRS-detected leg asymmetry is due
      to the specific demands of short-track speed skating. However, heterogeneity
      between individuals is not specific to the mode of exercise. Whether this is a
      result of genuine differences in physiology or a reflection of differences in the
      optical properties of the leg remains to be determined.

PMID- 22879019
TI  - Modelling cerebrovascular reactivity: a novel near-infrared biomarker of cerebral
      autoregulation?
AB  - Understanding changes in cerebral oxygenation, haemodynamics and metabolism holds
      the key to individualised, optimised therapy after acute brain injury. Near
      infrared spectroscopy (NIRS) offers the potential for non-invasive, continuous
      bedside measurement of surrogates for these processes. Interest has grown in
      applying this technique to interpret cerebrovascular pressure reactivity (CVPR),
      a surrogate of the brain's ability to autoregulate blood flow. We describe a
      physiological model-based approach to NIRS interpretation which predicts
      autoregulatory efficiency from a model parameter k_aut. Data from three
      critically brain-injured patients exhibiting a change in CVPR were investigated.
      An optimal value for k_aut was determined to minimise the difference between
      measured and simulated outputs. Optimal values for k_aut appropriately tracked
      changes in CVPR under most circumstances. Further development of this technique
      could be used to track CVPR providing targets for individualised management of
      patients with altered vascular reactivity, minimising secondary neurological
      insults.

PMID- 22879020
TI  - Oxygen delivery deficit in exercise with rapid ascent to high altitude.
AB  - This study of high altitude physiology was undertaken during an 11-day expedition
      to the Himalaya with ascent to Annapurna base camp (4,130 m) reaching it on the
      sixth day. Fourteen male UK residents (13 aged 16-17 years; 1 adult) measured
      arterial oxygen saturation (SaO(2)) and heart rate (HR) at rest and at 2 min
      exercise (30 cm step), daily, after arrival at each altitude. Precision was
      limited by availability of only one oximeter (CMS50-DLP model, Contec Medical
      Systems, Qinhuangdao, P.R. China). Mean HR correlated (negatively) with SaO(2)
      both for rest (HR = -1.7974 * SaO(2)% + 236.33, r = 0.841, p = 0.001) and
      exercise (HR = -0.8834 * SaO(2)% + 226.14, r = 0.711 p < 0.02). Four subjects
      individually showed significant HR/SaO(2) correlations at rest (nos. 10, 11, 12
      and 13) and one, subject 11, in exercise. SaO2 in exercise was lower than at rest
      (SaO(2), exercise = 1.5835 * SaO(2), rest - 59.177, r = 0.987, p < 0.001). The
      product, HR * SaO(2), calculated as a surrogate for oxygen delivery (DO(2),
      Brierley et al., Adv Exp Med Biol 737:207-212, 2012), from mean values was
      approximately constant for rest, suggesting good cardiac output (CO) compensation
      for de-saturation. The HR * SaO(2) for exercise, however, showed a dramatic fall
      at the highest altitude. Since this deficit occurred at the highest altitude,
      following 2 days of rapid ascent, there was probably impairment of adequate
      oxygen delivery (DO(2)) at this point. Correlation, HR versus SaO(2) for
      exercise, was highly significant, with greater significance (HR = -1.798 * SaO(2)
      + 281.83, r = 0.769, p = 0.01) on omission of the values for the highest ascent
      point (4,130 m), where the reduced HR * SaO(2) occurred. In conclusion, oxygen
      delivery is sustained well here except where there are the extra stresses of
      rapid ascent and exercise.

PMID- 22879022
TI  - Effect of spinal anesthesia for elective cesarean section on cerebral blood
      oxygenation changes: comparison of hyperbaric and isobaric bupivacaine.
AB  - We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation
      changes in subjects undergoing cesarean section under spinal anesthesia (SP) with
      hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I,
      15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within
      20 min after SP were significantly lower than the baseline values. In contrast,
      there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in
      group I after SP. Total-Hb and MBP in group H were significantly lower than those
      in group I within 10 min after SP. There was no significant change of deoxy-Hb,
      tissue oxygen index, or heart rate from baseline in either of the groups. These
      results suggest that isobaric bupivacaine may be superior to hyperbaric
      bupivacaine for preventing a decrease of maternal cerebral blood flow after SP
      for cesarean section.

PMID- 22879021
TI  - Oscillations in cerebral haemodynamics in patients with falciparum malaria.
AB  - Spontaneous oscillations in cerebral haemodynamics studied with near-infrared
      spectroscopy (NIRS), become impaired in several pathological conditions. We
      assessed the spectral characteristics of these oscillations in 20 patients with
      falciparum malaria admitted to Ispat General Hospital, Rourkela, India.
      Monitoring included continuous frontal lobe NIRS recordings within 24 h of
      admission (Day 0), together with single measurements of a number of clinical and
      chemical markers recorded on admission. Seven patients returned for follow-up
      measurements on recovery (FU). A 2,048 sampling-point segment of oxygenated
      haemoglobin concentration ([DeltaHbO(2)]) data was subjected to Fourier analysis
      per patient, and power spectral density was derived over the very low frequency
      (VLF: 0.02-0.04 Hz), low frequency (LF: 0.04-0.15 Hz) and high frequency (HF:
      0.15-0.4 Hz) bands. At Day 0, VLF spectral power was 21.1 +/- 16.4, LF power 7.2
      +/- 4.6 and HF power 2.6 +/- 5.0, with VLF power being statistically
      significantly higher than LF and HF (P < 0.005). VLF power tended to decrease in
      the severely ill patients and correlated negatively with heart rate (r = 0.57, P
      < 0.01), while LF power correlated positively with aural body temperature (r =
      0.49, P < 0.05). In all but one of the patients who returned for FU measurements,
      VLF power increased after recovery. This may be related to autonomic dysfunction
      in severe malaria, a topic of little research to date. The present study
      demonstrated that application of NIRS in a resource-poor setting is feasible and
      has potential as a research tool.

PMID- 22879023
TI  - DCX-expressing neurons decrease in the retrosplenial cortex after global brain
      ischemia.
AB  - Many studies have demonstrated cognitive function disorders including space
      learning disorders after global brain ischemia (GBI). Previous research on space
      perception and learning has indicated that the retrosplenial cortex (RS) is
      strongly involved. We performed immunostaining with doublecortin (DCX) for
      neurons with plasticity potential in the RS and investigated the neuronal numbers
      to assess the changes of plasticity in the RS following GBI. We employed male
      Sprague-Dawley rats and carried out bilateral carotid arterial occlusion for 10
      min as a GBI model (control, n = 5; GBI model, n = 5). We counted the right and
      left hemispheres separately on two serial sections, for a total of four regions
      per animal to examine the differences in expression related to GBI. Additionally,
      we performed Fluoro-Jade B (FJB) staining to investigate the cause of any DCX
      expressing neuron decrease. The total number of DCX-expressing neurons was 1,652
      and 912 in the controls and GBI model, respectively. The mean number of DCX
      expressing neurons per unit area was significantly lower in the GBI model than in
      the controls. FJB positive neurons were not found in the RS, while many were
      present in the -hippocampus CA1 after GBI. The decrease of DCX-expressing neurons
      in the RS indicated a plasticity decrease following GBI. The lack of FJB positive
      neurons in the RS after GBI suggested that the decrease of DCX-expressing neurons
      in the RS was not due to neuronal cell death in contrast to the hippocampus CA1,
      while the FJB positive neurons in the hippocampus indicated a delayed neuronal
      cell death as observed in many previous studies.

PMID- 22879024
TI  - Calibration and validation scheme for in vivo spectroscopic imaging of tissue
      oxygenation.
AB  - The determination of the level of oxygenation in optically accessible tissues
      using multispectral or hyperspectral imaging (HSI) of oxy- and deoxyhemoglobin
      has special appeal in clinical work due to its noninvasiveness, ease of use, and
      capability of providing molecular and anatomical information at near video rates
      during surgery. In this paper we refer to an example of the use of HSI in
      monitoring oxygenation of kidneys during partial nephrectomy. In a study using
      porcine models, it was found that artery-only clamping left the kidney better
      oxygenated, as opposed to simultaneously clamping the artery and the vein. A
      subsequent study correlates gradations in blood flow by partial clamping during
      the surgical procedure with postoperative renal function via assessment of
      creatinine level. We discuss the various contributions to the uncertainty of the
      oxygen saturation measured by this remote-sensing imaging technique in medical
      application.

PMID- 22879025
TI  - Considering the vascular hypothesis of Alzheimer's disease: effect of copper
      associated amyloid on red blood cells.
AB  - The vascular hypothesis of Alzheimer's disease (AD) considers cerebral
      hypoperfusion as a primary trigger for neuronal dysfunction. We have previously
      reported that red blood cells (RBCs) bind amyloid, which are the characteristic
      deposits found in AD brains, and interact with amyloid on the vasculature [1-3].
      Oxidative stress triggered by these RBC/amyloid interactions could impair oxygen
      delivery. Recent literature has implicated copper bound amyloid-beta peptide
      (CuAbeta) and the associated production of reactive oxygen species (ROS) as one
      of the primary factors contributing to AD pathology. In this work, we have
      investigated CuAbeta generated RBC oxidative stress. Abeta(1-40) peptide with a
      stoichiometric amount of copper bound was produced and compared to the metal-free
      form of the peptide. Different aggregation states of the peptides were isolated
      and incubated with RBCs for 15 h. Interestingly, CuAbeta stimulated a pronounced
      increase in red cell oxidative stress as indicated by increased hemoglobin (Hb)
      oxidation, increased formation of fluorescent heme degradation products, and a
      decrease in RBC deformability. These findings demonstrate a potential role for
      CuAbeta in promoting vascular oxidative stress leading to impaired cerebral
      oxygen delivery, which may contribute to neurodegeneration associated with AD.

PMID- 22879026
TI  - The role of mitochondrial proteomic analysis in radiological accidents and
      terrorism.
AB  - In the wake of the 9/11 terrorist attacks and the recent Level 7 nuclear event at
      the Fukushima Daiichi plant, there has been heightened awareness of the
      possibility of radiological terrorism and accidents and the need for techniques
      to estimate radiation levels after such events. A number of approaches to
      monitoring radiation using biological markers have been published, including
      physical techniques, cytogenetic approaches, and direct, DNA-analysis approaches.
      Each approach has the potential to provide information that may be applied to the
      triage of an exposed population, but problems with development and application of
      devices or lengthy analyses limit their potential for widespread application. We
      present a post-irradiation observation with the potential for development into a
      rapid point-of-care device. Using simple mitochondrial proteomic analysis, we
      investigated irradiated and nonirradiated murine mitochondria and identified a
      protein mobility shift occurring at 2-3 Gy. We discuss the implications of this
      finding both in terms of possible mechanisms and potential applications in bio
      radiation monitoring.

PMID- 22879027
TI  - Alteration of plasma galactose/N-acetylgalactosamine level after irradiation.
AB  - Although glycoproteins possess a variety of functional and structural roles in
      intracellular and intercellular activities, the effect of ionizing radiation (IR)
      on glycosylation is largely unknown. To explore this effect, we established a
      sandwich assay in which PHA-L, a phytohaemagglutinin that agglutinates
      leukocytes, was used as a coating layer to capture glycoproteins containing
      complex oligosaccharides; the bound glycoproteins were then measured. C57BL/6
      mice were exposed to 0, 3, 6, or 10 Gy, and the plasma was collected at 6, 12,
      18, 24, 48, 72, or 168 h and then analyzed for galactose/N-acetylgalactosamine
      (Gal/GalNAc) containing proteins. We found that (1) the sandwich assay accurately
      measured the level of glycoproteins, (2) 6-12 h after IR, the amount of
      glycoproteins containing GalNAc increased, and (3) at 72 and 168 h, 10 Gy was
      associated with a decrease in Gal/GalNAc. These IR-induced alterations might
      relate to the release of glycoproteins into the blood and the damage of the
      proteins and genes that are related to the glycosylation process.

PMID- 22879028
TI  - Fibroblast growth factor-peptide promotes bone marrow recovery after irradiation.
AB  - Various members of the fibroblast growth factor (FGF) family mitigate radiation
      induced damage. We designed and synthesized the binding domain peptide of FGF-2
      (FGF-P) with a dimer form resistant to peptidase and examined its mitigatory
      effect on murine bone marrow cells. NIH Swiss mice were exposed to different
      doses of total body irradiation (TBI) and treated with ten doses of 5 mg/kg FGF
      P. We achieved the following results: (1) FGF-P stimulated the growth of bone
      marrow cells harvested from mice exposed to 3 Gy; (2) on day 25 after 6 Gy TBI,
      the number of leukocytes and granulocytes was higher in the FGF-P group than in
      the vehicle-alone group; (3) FGF-P significantly increased the number of pro-B
      and pre-B cells; and (4) FGF-P treatment in vivo increased the long-term
      hematopoietic stem cells (LT-HSC) in bone marrow. These data reveal the
      underlying mechanism by which FGF-P rescued a significant percentage of the
      exposed mice. The increase of LT-HSC in bone marrow leads to a concomitant
      increase of pro-B and pre-B cells followed by leukocytes and granulocytes, which
      in turn enhance immunity against infection.

PMID- 22879029
TI  - Dynamic two-photon imaging of cerebral microcirculation using fluorescently
      labeled red blood cells and plasma.
AB  - To explore the spatiotemporal dynamics of red blood cells (RBCs) and plasma flow
      in three-dimensional (3D) microvascular networks of the cerebral cortex, we
      performed two-photon microscopic imaging of the cortical microvasculature in
      genetically engineered rats in which the RBCs endogenously express green
      fluorescent protein (GFP). Water-soluble quantum dots (Qdots) were injected
      intravenously into the animals to label the plasma, and concurrent imaging was
      performed for GFP-RBCs and Qdot plasma. The RBC and plasma distributions were
      compared between resting state and forepaw stimulation-induced neural activation.
      The RBC and plasma images showed detectable signals up to a depth of 0.4 and 0.6
      mm from the cortical surface, respectively. A thicker plasma layer (2-5 MUm) was
      seen in venous vessels relative to the arterial vessels. In response to neural
      activation, the RBCs were redistributed among the parenchymal capillary networks.
      In addition, individual capillaries showed a variable ratio of RBC and plasma
      distributions before and after activation, indicative of dynamic changes of
      hematocrit in single capillaries. These results demonstrate that this transgenic
      animal model may be useful in further investigating the mechanism that controls
      dynamic RBC flow in single capillaries and among multiple capillary networks of
      the cerebral microcirculation.

PMID- 22879030
TI  - The effect of basic assumptions on the tissue oxygen saturation value of near
      infrared spectroscopy.
AB  - Tissue oxygen saturation (StO(2)), a potentially important parameter in clinical
      practice, can be measured by near infrared spectroscopy (NIRS). Various devices
      use the multi-distance approach based on the diffusion approximation of the
      radiative transport equation [1, 2]. When determining the absorption coefficient
      (MU (a)) by the slope over multiple distances a common assumption is to neglect
      MU (a) in the diffusion constant, or to assume the scattering coefficient (MU(s))
      to be constant over the wavelength. Also the water influence can be modeled by
      simply subtracting a water term from the absorption. This gives five approaches
      A1-A5. The aim was to test how these different methods influence the StO(2)
      values. One data set of 30 newborn infants measured on the head and another of
      eight adults measured on the nondominant forearm were analyzed. The calculated
      average StO(2) values measured on the head were (mean +/- SD): A1: 79.99 +/-
      4.47%, A2: 81.44 +/- 4.08%, A3: 84.77 +/- 4.87%, A4: 85.69 +/- 4.38%, and A5:
      72.85 +/- 4.81%. The StO(2) values for the adult forearms are: A1: 58.14 +/-
      5.69%, A2: 73.85 +/- 4.77%, A3: 58.99 +/- 5.67%, A4: 74.21 +/- 4.76%, and A5:
      63.49 +/- 5.11%. Our results indicate that StO(2) depends strongly on the
      assumptions. Since StO(2) is an absolute value, comparability between different
      studies is reduced if the assumptions of the algorithms are not published.

PMID- 22879031
TI  - The effect of sudden depressurization on pilots at cruising altitude.
AB  - The standard flight level for commercial airliners is ~12 km (40 kft; air
      pressure: ~ 200 hPa), the maximum certification altitude of modern airliners may
      be as high as 43-45 kft. Loss of structural integrity of an airplane may result
      in sudden depressurization of the cabin potentially leading to hypoxia with loss
      of consciousness of the pilots. Specialized breathing masks supply the pilots
      with oxygen. The aim of this study was to experimentally simulate such sudden
      depressurization to maximum design altitude in a pressure chamber while measuring
      the arterial and brain oxygenation saturation (SaO(2) and StO(2)) of the pilots.
      Ten healthy subjects with a median age of 50 (range 29-70) years were placed in a
      pressure chamber, breathing air from a cockpit mask. Pressure was reduced from
      753 to 148 hPa within 20 s, and the test mask was switched to pure O(2) within 2
      s after initiation of depressurization. During the whole procedure SaO(2) and
      StO(2) were measured by pulse oximetry, respectively near-infrared spectroscopy
      (NIRS; in-house built prototype) of the left frontal cortex. During the
      depressurization the SaO(2) dropped from median 93% (range 91-98%) to 78% (62
      92%) by 16% (6-30%), while StO(2) decreased from 62% (47-67%) to 57% (43-62%) by
      5% (3-14%). Considerable drops in oxygenation were observed during sudden
      depressurization. The inter-subject variability was high, for SaO(2) depending on
      the subjects' ability to preoxygenate before the depressurization. The drop in
      StO(2) was lower than the one in SaO(2) maybe due to compensation in blood flow.

PMID- 22879032
TI  - Hypoxia in the diabetic kidney is independent of advanced glycation end-products.
AB  - Sustained hyperglycemia is closely associated with increased risk to develop
      nephropathy. We have previously reported alterations in the intrarenal oxygen
      metabolism already after the early onset of diabetes. Furthermore, formation of
      advanced glycation end-products (AGE) is postulated as a major contributor to
      diabetic nephropathy. We therefore investigated the possible relationship between
      altered oxygen metabolism and AGE in diabetic kidneys.Normoglycemic and
      streptozotocin-diabetic rats with and without chronic treatment with
      aminoguanidine (AGE inhibitor; 600 mg/kg bw/24 h in drinking water) or L-N(6)-(1
      Iminoethyl)lysine (L-NIL, iNOS inhibitor, 1 mg/kg bw/24 h in drinking water) were
      studied 2 weeks after induction of diabetes. Glomerular filtration rate (GFR) was
      estimated by inulin clearance, oxygen tension (pO(2)) and interstitial pH by
      microelectrodes and regional renal blood flow (RBF) by laser-Doppler.
      Histological changes were evaluated on fixed tissue.Glomerular hyperfiltration
      was unaffected by aminoguanidine, whereas L-NIL normalized GFR in diabetic rats.
      pO(2) and interstitial pH, but not RBF, were lower in both kidney cortex and
      medulla compared to control rats, but was unaffected by both chronic treatments.
      Urinary protein excretion was higher in diabetic rats and unaffected by L-NIL,
      whereas aminoguanidine paradoxically increased this parameter. Damage scores were
      similar in all groups.In conclusion, diabetes-induced alterations in intrarenal
      oxygen metabolism are independent of the AGE pathway, and precede any
      morphological changes. These findings highlight the early stage of diabetes as
      being a metabolic disorder also in the kidney.

PMID- 22879033
TI  - Tumor oxygen measurements and personalized medicine.
AB  - Tumor hypoxia is probably the most important not yet measurable factor that
      predicts the outcome of cancer therapy. Hypoxic tumors are resistant to
      radiation, chemotherapy, and surgery. They signal tumor cells to grow, invade,
      survive cytotoxic-factor assault, and increase metastatic activity. Therapies
      aimed at reversing hypoxia-related treatment resistance or normalizing hypoxia
      are proven effective with level 1 evidence. The weak link remains the lack of
      satisfactory methods of measurement of tumor oxygenation.

PMID- 22879034
TI  - Wavelet cross-correlation to investigate regional variations in cerebral
      oxygenation in infants supported on extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation can potentially affect cerebral blood flow
      dynamics and consequently influence cerebral autoregulation. We applied wavelet
      cross-correlation (WCC) between multichannel cerebral oxyhemoglobin concentration
      (HbO(2)) and mean arterial pressure (MAP), to assess regional variations in
      cerebral autoregulation. Six infants on veno-arterial (VA) ECMO were studied
      during sequential changes in the ECMO flows. WCC between MAP and HbO(2) for each
      flow period and each channel was calculated within three different frequency
      (wavelet scale) bands centered around 0.1, 0.16, and 0.3 Hz chosen to represent
      low frequency oscillations, ventilation, and respiration rates, respectively. The
      group data showed a relationship between maximum WCC and ECMO flow. During
      changes in ECMO flow, statistically significant differences in maximum WCC were
      found between right and left hemispheres. WCC between HbO(2) and MAP provides a
      useful method to investigate the dynamics of cerebral autoregulation during ECMO.
      Manipulations of ECMO flows are associated with regional changes in cerebral
      autoregulation which may potentially have an important bearing on clinical
      outcome.

PMID- 22879035
TI  - Association of the red cell distribution width with red blood cell deformability.
AB  - The red cell distribution width (RDW) is a component of the automated complete
      blood count (CBC) that quantifies heterogeneity in the size of circulating
      erythrocytes. Higher RDW values reflect greater variation in red blood cell (RBC)
      volumes and are associated with increased risk for cardiovascular disease (CVD)
      events. The mechanisms underlying this association are unclear, but RBC
      deformability might play a role. CBCs were assessed in 293 adults who were
      clinically examined. RBC deformability (expressed as the elongation index) was
      measured using a microfluidic slit-flow ektacytometer. Multivariate regression
      analysis identified a clear threshold effect whereby RDW values above 14.0% were
      significantly associated with decreased RBC deformability (beta = -0.24; p =
      0.003). This association was stronger after excluding anemic participants (beta =
      -0.40; p = 0.008). Greater variation in RBC volumes (increased RDW) is associated
      with decreased RBC deformability, which can impair blood flow through the
      microcirculation. The resultant hypoxia may help to explain the previously
      reported increased risk for CVD events associated with elevated RDW.

PMID- 22879036
TI  - Kidney function after in vivo gene silencing of uncoupling protein-2 in
      streptozotocin-induced diabetic rats.
AB  - Kidney uncoupling protein 2 (UCP-2) increases in streptozotocin-induced diabetes,
      resulting in mitochondria uncoupling, i.e., increased oxygen consumption
      unrelated to active transport. The present study aimed to investigate the role of
      UCP-2 for normal and diabetic kidney function utilizing small interference RNA
      (siRNA) to reduce protein expression. Diabetic animals had increased glomerular
      filtration rate and kidney oxygen consumption, resulting in decreased oxygen
      tension and transported sodium per consumed oxygen. UCP-2 protein levels
      decreased 2 and 50% after UCP-2 siRNA administration in control and diabetic
      animals respectively. Kidney function was unaffected by in vivo siRNA-mediated
      gene silencing of UCP-2. The reason for the lack of effect of reducing UCP-2 is
      presently unknown but may involve compensatory mitochondrial uncoupling by the
      adenosine nucleotide transporter.

PMID- 22879037
TI  - Adenosine A2 receptor-mediated regulation of renal hemodynamics and glomerular
      filtration rate is abolished in diabetes.
AB  - Alterations in glomerular filtration rate (GFR) are one of the earliest
      indications of altered kidney function in diabetes. Adenosine regulates GFR
      through tubuloglomerular feedback mechanism acting on adenosine A1 receptor. In
      addition, adenosine can directly regulate vascular tone by acting on A1 and A2
      receptors expressed in afferent and efferent arterioles. Opposite to A1
      receptors, A2 receptors mediate vasorelaxation. This study investigates the
      involvement of adenosine A2 receptors in regulation of renal blood flow (RBF) and
      GFR in control and diabetic kidneys. GFR was measured by inulin clearance and RBF
      by a transonic flow probe placed around the renal artery. Measurements were
      performed in isoflurane-anesthetized normoglycemic and alloxan-diabetic C57BL/6
      mice during baseline and after acute administration of 3,7-dimethyl-1
      propargylxanthine (DMPX), a selective A2 receptor antagonist. GFR and RBF were
      lower in diabetic mice compared to control (258 +/- 61 vs. 443 +/- 33 MUl min(-1)
      and 1,083 +/- 51 vs. 1,405 +/- 78 MUl min(-1)). In control animals, DMPX
      decreased RBF by -6%, whereas GFR increased +44%. DMPX had no effects on GFR and
      RBF in diabetic mice. Sodium excretion increased in diabetic mice after A2
      receptor blockade (+78%). In conclusion, adenosine acting on A2 receptors
      mediates an efferent arteriolar dilatation which reduces filtration fraction (FF)
      and maintains GFR within normal range in normoglycemic mice. However, this
      regulation is absent in diabetic mice, which may contribute to reduced oxygen
      availability in the diabetic kidney.

PMID- 22879038
TI  - Can mitochondrial cytochrome oxidase mediate hypoxic vasodilation via nitric
      oxide metabolism?
AB  - The brain responds to hypoxia with an increase in cerebral blood flow (CBF). Many
      mechanisms have been proposed for this hypoxic vasodilation, but none has gained
      universal acceptance. Although there is some disagreement about the shape of the
      relationship between arterial oxygen partial pressure (PaO(2)) and CBF, it is
      generally agreed that CBF does not increase until the PaO(2) reaches a threshold
      value. We used a previously published computational model of brain oxygen
      transport and metabolism (BRAINSIGNALS) to test possible molecular mechanisms for
      such a threshold phenomenon. One suggestion has been that a decrease in the
      metabolism of nitric oxide by mitochondrial cytochrome c oxidase (CCO) at low
      PaO(2) could be responsible for raising NO levels and the consequent triggering
      of the hypoxic blood flow increase. We tested the plausibility of this mechanism
      using the known rate constants for NO interactions with CCO. We showed that the
      shape of the CBF-PaO(2) curve could indeed by reproduced, but only if NO
      production by the enzyme nitric oxide synthase had a very low Michaelis constant
      K (m) for oxygen. Even then, in the current version of BRAINSIGNALS the NO
      induced CBF rise occurs at much lower PaO(2) than is consistent with the in vivo
      data.

PMID- 22879039
TI  - Effects of occlusal disharmony on working memory performance and prefrontal
      cortex activity induced by working memory tasks measured by NIRS.
AB  - The effects of artificial occlusal disharmony (AOD) on working memory function
      and prefrontal cortex (PFC) activity in the elderly were examined. We evaluated
      working memory function using the modified Sternberg test (ST). We measured
      activity in the bilateral PFC during ST using near-infrared spectroscopy (NIRS)
      before and after AOD: the mandibular position was displaced by a splint for 10
      min. AOD caused a gradual increase of oxyhemoglobin (oxy-Hb) in the bilateral
      PFC. The response time of ST (six digits) after AOD was longer than that before
      AOD. The oxy-Hb increase during ST after AOD was smaller than that before AOD.
      These results indicate that short-term physical stress caused by AOD decreased
      working memory function in elderly subjects, associated with a decrease of the
      evoked PFC activity during working memory function.

PMID- 22879040
TI  - Biological maintenance of distal vein arterialization.
AB  - Eleven weeks after surgery, a fine microvessel network was seen in the feet of
      patients with arteriosclerosis obliterans treated by distal vein arterialization.
      A possible mechanism for establishment of blood flow to, and biological
      maintenance of, the graft in the foot, in relation to oxygen consumption rate
      during walking was investigated, using Krogh's tissue cylinder model. Our
      calculations showed that the increase in oxygen consumption rate of the muscle
      when patients walked would reduce the size of the oxygen front in the tissue
      cylinder, thus producing small, transient hypoxic regions in skeletal foot
      muscle. Such muscle hypoxia, although localized, could stimulate synthesis of
      vascular endothelial growth factor and facilitate angiogenesis in the grafted
      tissue. The architecture of fine microvessel networks observed in the foot by
      angiography seems consistent with this supposition and, moreover, suggests that
      the reinstatement of blood vessel networks in the foot tissues after grafting is
      supported by "normal" biological mechanisms.

PMID- 22879041
TI  - Bayesian STAI anxiety index predictions based on prefrontal cortex NIRS data for
      the resting state.
AB  - Several distinctive activity patterns have been observed in the brain at rest.
      The aim of this study was to determine whether the STAI index can be predicted
      from changes in the oxy- and deoxy-hemoglobin (Hb) concentrations by using two
      channel prefrontal cortex (PFC) NIRS data for the resting state. The study
      population comprised 19 subjects. Each subject performed four trials, each of
      which consisted of resting with no task for 3 min. Data were acquired using a
      portable NIRS device equipped with two channels. The prediction algorithm was
      derived within a Bayesian machine learning framework. The prediction errors for
      seven subjects were not greater than 5.0. Because the STAI index varied between
      20 and 80, these predictions appeared reasonable. The present method allowed
      prediction of mental status based on the NIRS data at resting condition obtained
      in the PFC.

PMID- 22879042
TI  - The effect of venous and arterial occlusion of the arm on changes in tissue
      hemodynamics, oxygenation, and ultra-weak photon emission.
AB  - Ultra-weak photon emission (UPE) is a general feature of living -biological
      systems. To gain further insights into the origin of UPE and its physiological
      significance, the aim of the present study was to investigate the connection
      between hemodynamics (HD), oxygenation (OX), and UPE. Therefore, during venous
      and arterial occlusion (VO, AO), changes of UPE and surrogates of HD as well as
      OX were measured simultaneously using two photomultipliers and near-infrared
      spectroscopy, respectively. We showed that (1) changes in UPE correlate
      significantly nonlinearly with changes in oxyhemoglobin (Delta[O(2)Hb]),
      deoxyhemoglobin (Delta[HHb]), and hemoglobin difference (Delta[HbD] =
      Delta[O(2)Hb]-Delta[HHb]), indicating a complex association between UPE and
      tissue HD/OX; (2) UPE decreases significantly during AO but not during VO; (3)
      UPE increases significantly after AO; and (4) the view that ROS are the source of
      UPE is generally supported by the present study, although some findings remain
      unexplained in the context of the theory of ROS-mediated UPE generation. In
      conclusion, the present study revealed new insights into the interplay between
      HD, OX, and UPE and opens up new questions that have to be addressed by future
      studies.

PMID- 22879043
TI  - Metabolic network analysis of DB1 melanoma cells: how much energy is derived from
      aerobic glycolysis?
AB  - A network model has been developed for analysis of tumor glucose metabolism from
      (13)C MRS isotope exchange kinetic data. Data were obtained from DB1 melanoma
      cells grown on polystyrene microcarrier beads contained in a 20-mm diameter
      perfusion chamber in a 9.4 T Varian NMR spectrometer; the cells were perfused
      with 26 mM [1,6-(13)C(2)]glucose under normoxic conditions and 37 degrees C and
      monitored by (13)C NMR spectroscopy for 6 h. The model consists of ~150
      differential equations in the cumomer formalism describing glucose and lactate
      transport, glycolysis, TCA cycle, pyruvate cycling, the pentose shunt, lactate
      dehydrogenase, the malate-aspartate and glycerophosphate shuttles, and various
      anaplerotic pathways. The rate of oxygen consumption (CMRO(2)) was measured
      polarographically by monitoring differences in pO(2). The model was validated by
      excellent agreement between model predicted and experimentally measured values of
      CMRO(2) and glutamate pool size. Assuming a P/O ratio of 2.5 for NADH and 1.5 for
      FADH2, ATP production was estimated as 46% glycolytic and 54% mitochondrial based
      on average values of CMRO(2) and glycolytic flux (two experiments).

PMID- 22879044
TI  - Muscle oxygen saturation heterogeneity among leg muscles during ramp exercise.
AB  - We examined whether O(2) saturation in several leg muscles changes as exercise
      intensity increases. Twelve healthy young males performed 20 W/min ramp bicycle
      exercise until exhaustion. Pulmonary O(2) uptake (VO(2)) was monitored
      continuously during the experiments to determine peak oxygen uptake. Muscle O(2)
      saturation (SmO(2)) was also monitored continuously at the belly of the vastus
      lateralis (VL), rectus femoris, vastus medialis, biceps femoris, gastrocnemius
      lateralis, gastrocnemius medialis, and tibialis anterior by near-infrared spatial
      resolved spectroscopy. Although the VL muscle mainly contributes during cycling
      exercise, deoxygenation was enhanced not only in the VL muscle but also in the
      other thigh muscles and lower leg muscles with increased exercise intensity.
      Furthermore, SmO(2) response during ramp cycling exercise differed considerably
      between leg muscles.

PMID- 22879045
TI  - PET imaging of the impact of extracellular pH and MAP kinases on the p
      glycoprotein (Pgp) activity.
AB  - The functional activity of p-glycoprotein (Pgp) can be increased in vitro by an
      extracellular acidosis via activation of MAP kinases (p38, ERK1/2). In order to
      study these effects in vivo a new (68)Ga-labeled PET tracer was developed which
      serves as a substrate of the Pgp and therefore indirectly mirrors the Pgp
      activity. For in vivo studies, experimental tumors were imaged under acidic
      conditions (inspiratory hypoxia, injection of lactic acid) and during inhibition
      of MAP kinases in a MU-PET system. In vitro, [(68)Ga]MFL6.MZ showed an
      accumulation within the cells of about 20% which was increased to 30% by Pgp
      inhibition. In solid tumors a marked tracer uptake was observed showing spatial
      heterogeneity. When the tumors were acidified, the PET tracer accumulation was
      reduced by 20-30%. Changing the inspiratory O(2)-fraction to 8% led dynamically
      to a decrease in pH and in parallel to a reduced tracer concentration. Inhibition
      of the p38 pathway reduced the Pgp transport rate. The new (68)Ga-labeled tracer
      is suitable for PET imaging of the tissue Pgp activity. In vivo imaging reveals
      that an acidosis activates the Pgp markedly, a mechanism in which the p38-MAPK
      pathway seems to play an important role.

PMID- 22879046
TI  - Meconium and transitional stools may cause interference with near-infrared
      spectroscopy measurements of intestinal oxygen saturation in preterm infants.
AB  - In a pilot study, we found that the NIRS measurements were highly variable and
      dramatically decreased or disappeared sporadically while monitoring gastro
      intestinal (GI) StO(2) on preterm neonates. We hypothesized that the light
      absorption characteristics of different neonatal and infant stool types may be
      interfering with NIRS GI measurements. METHODS: Meconium, transitional, and
      mature stool samples collected from preterm neonates and older infants (ranging
      from a few days to weeks in age) were analyzed by a bench-top spectrometer to
      measure light absorbance in the near infrared range (650-950 nm). RESULTS: Some
      meconium and transitional stool samples were noted to have a more marked increase
      in light absorbance as wavelength decreases towards 650 nm, when compared to more
      mature stools. When compared to the light absorbance spectra of deoxy-hemoglobin
      (Hb) and oxy-hemoglobin (HbO(2)), there is a high potential that Hb and HbO(2)
      may be erroneously calculated, resulting in falsely low GI StO(2). DISCUSSION:
      Meconium and green colored transitional stools demonstrate a light absorbance
      spectra that may interfere with NIRS GI measurements, possibly due to their
      higher biliverdin content, which exhibits a broad spectral absorption peak at 660
      nm. Caution is warranted in interpreting GI StO(2) NIRS results in neonates still
      passing meconium and transitional stools until NIRS-based tissue oximeters to
      measure GI StO(2) can compensate for the presence of these stool types.

PMID- 22879047
TI  - Acute effects of physical exercise on prefrontal cortex activity in older adults:
      a functional near-infrared spectroscopy study.
AB  - We examined the acute effect of physical exercise on prefrontal cortex activity
      in older adults using functional near-infrared spectroscopy (NIRS). Fourteen
      older adults visited our laboratory twice: once for exercise and once for the
      control condition. On each visit, subjects performed working memory tasks before
      and after moderate intensity exercise with a cycling ergo-meter. We measured the
      NIRS response at the prefrontal cortex during the working memory task. We found
      that physical exercise improved behavioral performance of the working memory task
      compared with the control condition. Moreover, NIRS analysis showed that physical
      exercise enhanced the prefrontal cortex activity, especially in the left
      hemisphere, during the working memory task. These findings suggest that the
      moderate intensity exercise enhanced the prefrontal cortex activity associated
      with working memory performance in older adults.

PMID- 22879048
TI  - Blood flow and oxygenation status of prostate cancers.
AB  - Hypoxia is a characteristic of many solid tumors, can lead to the development of
      an aggressive phenotype and acquired treatment resistance, and is an independent,
      adverse prognostic indicator. In this literature review, we show that hypoxia is
      also a typical feature in prostate cancer (PC), the most commonly diagnosed
      cancer among men in most western countries. Data on blood flow (a major
      determinant of oxygenation status in malignancies) and on the oxygenation status
      (as assessed by O(2)-sensitive electrodes) are presented. Where possible, data on
      prostate cancers are compared to normal prostate (NP) tissue and benign prostate
      hyperplasia (BPH). The average blood flow rate in NP is 0.21 vs. 0.28 mL/g/min in
      BPH. Blood flow in PC is approximately three times higher than in NP (mean flow:
      0.64 mL/g/min) and shows pronounced intra- and inter-tumor variability. Despite
      relatively high flow rates in PC, the overall mean pO(2) in cancers is 6 mmHg
      compared to 26 mmHg in NP. As was the case with blood flow, tissue oxygenation
      was extremely heterogeneous with no clear dependency on a series of tumor
      (Gleason score, clinical size, androgen deprivation) and patient characteristics
      (serum PSA levels, age).

PMID- 22879049
TI  - Targeted delivery of VEGF to treat myocardial infarction.
AB  - Noninvasive injection of pro-angiogenic compounds such as vascular endothelial
      growth factor (VEGF) has shown promising results in regenerating cardiac
      microvasculature. However, these results have failed to translate into successful
      clinical trials in part due to the short half-life of VEGF in circulation.
      Increasing the dose of VEGF may increase its availability to the target tissue,
      but harmful side-effects remain a concern. Encapsulating and selectively
      targeting VEGF to the MI border zone may circumvent these problems. Anti-P
      selectin conjugated immunoliposomes containing VEGF were developed to target the
      infarct border zone in a rat MI model. Targeted VEGF therapy significantly
      improves vascularization and cardiac function after an infarction.

PMID- 22879050
TI  - Magnetic nanoparticles and thermally responsive polymer for targeted hyperthermia
      and sustained anti-cancer drug delivery.
AB  - A novel cancer treatment method is being designed using a combination of iron
      oxide (Fe(3)O(4)) nanoparticles (IONPs) and Pluronic F-127 (PF127). IONPs have
      been used for heating tumors via an alternating electromagnetic (AEM) field.
      PF127 is a polymer possessing thermo-reversible and concentration-dependent
      gelation properties in aqueous solutions. PF127, as a gel, is an attractive drug
      delivery vehicle due to its zero-order drug release property. The combination of
      IONPs and PF127 would allow both short-term, tumor-specific, hyperthermic
      treatment, and long-term sustained drug delivery. As a preliminary study, the
      gelling and heating properties of IONPs/PF127 mixtures were investigated: 18%
      (w/w) PF127 was found to be ideal for our purpose because it gels at 28.0 degrees
      C, i.e., it would be injectable at room temperature (20-25 degrees C) and forms
      gel upon injection into the body (37 degrees C). IONPs in PF127 showed little
      effect on gelation temperatures. The heating performance of IONPs in PF127
      slightly, but linearly decreased with PF127. In the IONP concentration range of
      0.01-0.05% (w/v) mixed with PF127 at 18% (w/w), the heating performance increased
      linearly with the increase in IONP concentration.

PMID- 22879051
TI  - NIR fluorophore-hollow gold nanosphere complex for cancer enzyme-triggered
      detection and hyperthermia.
AB  - Hollow gold nanospheres (HGN) may be delicately tuned to absorb near infrared
      light (NIR) by tailoring the diameter-to-shell ratio. This unique property can be
      utilized for enhancing the contrast for the NIR and X-ray/CT imaging, and also
      noninvasive and local, photothermal hyperthermia by conjugating cancer-targeting
      molecules on the particle surface. In addition, when an NIR fluorophore is placed
      on the surface of the NIR-tuned HGNs, the fluorescence can be significantly
      quenched due to the emitted light absorption by the HGNs. Combining the NIR
      fluorescence quenching property of HGNs and the enzyme secreting nature of
      cancer, we have developed a novel enzyme-triggered NIR contrast agent for cancer
      detection with high specificity. NIR fluorophore Cypate (Indocyanine Green based)
      was conjugated to HGN via a short spacer for fluorescence quenching. The spacer
      contains an enzyme-substrate-motif (G-G-R) that can be cleaved by urokinase-type
      plasminogen activator (uPA, a breast cancer enzyme). The nano-complex normally
      does not emit fluorescence but, in the presence of uPA, the fluorescence was
      restored, providing high specificity. The enzyme-specific emission allows us to
      characterize the nature of the cancer (e.g., invasive, metastatic, etc.). Once
      the cancer is detected, the same HGNs can be used to deliver heat to the cancer
      site for cancer-specific hyperthermia.

PMID- 22879052
TI  - Renal oxygenation and function of the rat kidney: effects of inspired oxygen and
      preglomerular oxygen shunting.
AB  - We investigated the hypothesis that a preglomerular diffusional shunt for O(2)
      stabilized renal PO(2) and that changes in intrarenal PO(2) determined nephron
      nitric oxide (NO) availability for blunting of the tubuloglomerular feedback
      (TGF) response. The inspired O(2) content of anesthetized rats was changed from
      normal (21%) to low (10%) or high (100%) for 30-45 min. Direct recordings of
      PO(2) in the lumens of proximal and distal tubules demonstrated significantly (P
      < 0.05) lower values at all sites in spontaneously hypertensive rats compared to
      normotensive Wistar Kyoto (WKY) rats. Low inspired O(2) did not change
      intratubular PO(2), but high inspired O(2) increased PO(2) modestly (25-50%; P <
      0.01) in both strains and at both sites. Addition of 7-nitroindazole (7-NI; 10(
      4) M) to artificial tubular fluid perfusing the loop of Henle of WKY nephrons to
      block neuronal (type 1) nitric oxide synthase in the macula densa increased TGF
      but this increase was less (P < 0.01) in nephrons of rats breathing high vs.
      normal inspired O(2) (1.8 +/- 0.4 vs. 3.4 +/- 0.3 mmHg; P < 0.01). In conclusion,
      the PO(2) in the renal tubules was effectively buffered from even extreme changes
      in arterial PO(2), consistent with a functionally important preglomerular O(2)
      diffusional shunt. However, high inspired PO(2) increased intratubular PO(2)
      sufficiently to blunt the effects of NO derived from the macula densa, likely
      reflecting bioinactivation of NO by reactive oxygen species generated at
      increased PO(2) levels. Thus, the preglomerular diffusional shunt appeared to
      stabilize intrarenal PO(2) during changes in arterial oxygen and to protect NO
      signaling within the kidney.

PMID- 22879053
TI  - Alteration of the inflammatory molecule network after irradiation of soft tissue.
AB  - Inflammatory molecules (IMs) play an important role in ionizing radiation (IR)
      induced soft tissue damage. The alteration of IMs as a function of time was
      studied with a protein array containing 62 IMs in mouse cutaneous soft tissues
      exposed to 30 Gy. The results showed that: (1) 2 days after irradiation, the
      levels of TGF-beta1, MIP-1gamma, IL-1alpha, and sTNF RI increased, while IGFBP-3,
      CXCL16, and IL-1beta decreased in IR skin as compared to control skin; (2) 21
      days after IR, TGF-beta1, and MIP-1 gamma, IL-1alpha remained high, while CXCL16
      and IL-1beta remained low; (3) 3 months after IR, the cytokine pattern exhibited
      reversals. The levels of MIP-1gamma decreased, while VCAM-1, IGFBP-3, and TGF
      beta1 production increased. The data indicated that: (a) IMs change as a function
      of time after soft tissue irradiation; (b) changing IM levels may reflect the
      altered balance of the cytokine network, leading to imbalance or homeostasis; and
      (c) an antibody-based protein array can be used to assess multiple IMs
      simultaneously, making it useful for bulk screening for changes in tissue
      cytokine levels.

PMID- 22879055
TI  - Early life hypoxic or hypoxic/hypercapnic stress alters acute ventilatory
      sensitivity in adult mice.
AB  - In this study we investigated the effect of early life conditioning (hypoxia +/-
      hypercapnia) on adult acute ventilatory sensitivity to hypoxia and hypercapnia.
      Mice were exposed to either hypoxia (5% O(2)) or hypoxia/hypercapnia (5% O(2)/8%
      CO(2)) in a normobaric chamber for 2 h at postnatal day 2 (P2), and then returned
      to normoxia. At 3 months of age, hypoxic ventilatory response (HVR) and
      hypercapnic ventilatory response (HCVR) were measured using a plethysmograph
      system. Results showed that HVR was significantly decreased in the P2-hypoxia
      mice but not in the P2 hypoxia/hypercapnia mice as compared to the P2-normoxic
      mice, respectively. However, HCVR was significantly decreased in the P2 hypoxia
      hypercapnia group but not in the P2-hypoxia group. These data suggest early
      postnatal hypoxic stress vs. hypoxic/hypercapnic stress plays different roles in
      fetal programming of the respiratory control system as shown by altered adult
      acute ventilatory sensitivity.

PMID- 22879054
TI  - Imaging the redox states of human breast cancer core biopsies.
AB  - Currently, the gold standard to establish benign vs. malignant breast tissue
      diagnosis requires an invasive biopsy followed by tissue fixation for subsequent
      histopathological examination. This process takes at least 24 h resulting in
      tissues that are less suitable for molecular, functional, or metabolic analysis.
      We have recently conducted redox scanning (cryogenic NADH/flavoprotein
      fluorescence imaging) on snap-frozen breast tissue biopsy samples obtained from
      human breast cancer patients at the time of their breast cancer surgery. The
      redox state was readily determined by the redox scanner at liquid nitrogen
      temperature with extraordinary sensitivity, giving oxidized flavoproteins (Fp) an
      up to tenfold discrimination of cancer to non-cancer of breast in our preliminary
      data. Our finding suggests that the identified metabolic parameters could
      discriminate between cancer and non-cancer breast tissues without subjecting
      tissues to fixatives. The remainder of the frozen tissue is available for
      additional analysis such as molecular analysis and conventional histopathology.
      We propose that this novel redox scanning procedure may assist in tissue
      diagnosis in ex vivo tissues.

PMID- 22879056
TI  - 3D analysis of intracortical microvasculature during chronic hypoxia in mouse
      brains.
AB  - The purpose of this study is to determine when and where the brain
      microvasculature changes its network in response to chronic hypoxia. To identify
      the hypoxia-induced structural adaptation, we longitudinally imaged cortical
      microvasculature at the same location within a mouse somatosensory cortex with
      two-photon microscopy repeatedly for up to 1 month during continuous exposure to
      hypoxia (either 8 or 10% oxygen conditions). The two-photon microscopy approach
      made it possible to track a 3D pathway from a cortical surface arteriole to a
      venule up to a depth of 0.8 mm from the cortical surface. The network pathway was
      then divided into individual vessel segments at the branches, and their diameters
      and lengths were measured. We observed 3-11 vessel segments between the
      penetrating arteriole and the emerging vein over the depths of 20-460 MUm within
      the 3D reconstructed image (0.46 * 0.46 * 0.80 mm(3)). The average length of the
      individual capillaries (<7 MUm in diameter) was 67 +/- 46 MUm, which was not
      influenced by hypoxia. In contrast, 1.4 +/- 0.3 and 1.2 +/- 0.2 fold increases of
      the capillary diameter were observed 1 week after exposure to 8 % and 10%
      hypoxia, respectively. At 3 weeks from the exposure, the capillary diameter
      reached 8.5 +/- 1.9 and 6.7 +/- 1.8 MUm in 8% and 10 % hypoxic conditions,
      respectively, which accounted for the 1.8 +/- 0.5 and 1.4 +/- 0.3 fold increases
      relative to those of the prehypoxic condition. The vasodilation of penetrating
      arterioles (1.4 +/- 0.2 and 1.2 +/- 0.2 fold increases) and emerging veins (1.3
      +/- 0.2 and 1.3 +/- 0.2 fold increases) showed relatively small diameter changes
      compared with the parenchymal capillaries. These findings indicate that
      parenchymal capillaries are the major site responding to the oxygen environment
      during chronic hypoxia.

PMID- 22879057
TI  - Contribution of brain glucose and ketone bodies to oxidative metabolism.
AB  - Ketone bodies are an alternative energy substrate to glucose in brain. Under
      conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose
      metabolism by partitioning glucose away from oxidative metabolism towards ketone
      body oxidation. In this study we assessed oxidative metabolism in ketotic rat
      brain using stable isotope mass spectrometry analysis. The contribution of
      glucose and ketone bodies to oxidative metabolism was studied in cortical brain
      homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis,
      rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard
      rodent chow for 3 weeks and then infused intravenously with tracers of [U-(13)C]
      glucose or [U-(13)C] acetoacetate for 60 min. The measured percent contribution
      of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the
      (13)C-label incorporation into acetyl-CoA. Using mass spectrometry (gas
      chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis,
      the fractional amount of substrate oxidation was measured as the M + 2 enrichment
      (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors,
      [U-(13)C]glucose or [U-(13)C] acetoacetate. RESULTS: the percent contribution of
      glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 +/-
      16.8 (mean% +/- SD) compared to the standard chow, 89.0 +/- 14.6. Acetoacetate
      oxidation was significantly higher with ketosis compared to standard chow, 41.7
      +/- 9.4 vs. 21.9 +/- 10.6. These data confer the high oxidative capacity for
      glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3
      weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non
      ketosis.

PMID- 22879058
TI  - Alteration of circulating mitochondrial DNA concentration after irradiation.
AB  - Mitochondrial DNA (mtDNA) is maternally inherited and controls the oxygen-related
      production of adenosine-5'-triphosphate, which is transported from the
      mitochondria to other cellular compartments and used as energy for cellular
      activities. The mtDNA is physically separated from nuclear DNA (nDNA). Ionizing
      radiation (IR) causes the release of both mtDNA and nDNA into circulation. Our
      previous study demonstrated that nDNA has potential to be a biodosimeter. In this
      study, branched DNA technology was used to explore the alteration pattern of
      mtDNA after IR. C57BL/6 mice were exposed to 0, 1.5, 3, 6, 8, or 10 Gy total body
      irradiation; thereafter, plasma mtDNA was assessed with samples collected at 3,
      6, 9, 15, 24, 48, 72, or 168 h. We found that: (1) the designed probesets were
      specific for mtDNA extracted from the liver, and they recognized the small amount
      of mtDNA mixed in the nDNA; (2) plasma mtDNA exhibited a statistically
      significant increase only at 6 h after 8 Gy irradiation. The alteration of mtDNA
      was not dose-dependent or time-dependent; hence, it is unlikely to be an
      effective biodosimeter.

PMID- 22879059
TI  - Salter-Harris type II proximal humerus injuries: state-of-the-art treatment.
AB  - Proximal epiphyseal injuries of the humerus represent a very low percentage of
      traumatic growth pathologies, 5 % of all fractures during childhood. In the
      literature, there have been only a limited number of clinical studies
      investigating these injuries, basically from an epidemiological point of view,
      focusing on the incidence of the different types of fractures. We report our
      experience of 6 young patients with Salter-Harris type II proximal humerus
      epiphyseal injuries adopting a minimally invasive surgical technique consisting
      of closed reduction and percutaneous fixation with Kirschner wires. At 2 years of
      follow-up, the results consisting in constant; disabilities of the arm, shoulder,
      and hand; simple shoulder test; and Visual Analogue Scale scores obtained have
      been excellent and all the patients come back to a normal life with sports
      practice and normal daily activities. The range of motion was completely restored
      without any deficit in abduction-adduction, flection-extension, or intra-extra
      rotation. No differences in anthropometric parameters were found with no case of
      malangulation, vascular, or neurological complications. Our data support with
      evidence how the close reduction internal fixation with K-wires treatment can
      give to the surgeons and the patients a better security about the correct
      fracture healing. Furthermore, with this article, we will provide a detailed
      review of the literature in order to define the state-of-the-art treatment to
      better face such a challenging skeletal injury.

PMID- 22879061
TI  - Introduction to purinergic signalling in the brain.
AB  - ATP is a cotransmitter with glutamate, noradrenaline, GABA, acetylcholine and
      dopamine in the brain. There is a widespread presence of both adenosine (P1) and
      P2 nucleotide receptors in the brain on both neurons and glial cells. Adenosine
      receptors play a major role in presynaptic neuromodulation, while P2X ionotropic
      receptors are involved in fast synaptic transmission and synaptic plasticity. P2Y
      G protein-coupled receptors are largely involved in presynaptic activities, as
      well as mediating long-term (trophic) signalling in cell proliferation,
      differentiation and death during development and regeneration. Both P1 and P2
      receptors participate in neuron-glial interactions. Purinergic signalling is
      involved in control of cerebral vascular tone and remodelling and has been
      implicated in learning and memory, locomotor and feeding behaviour and sleep.
      There is increasing interest in the involvement of purinergic signalling in the
      pathophysiology of the CNS, including trauma, ischaemia, epilepsy,
      neurodegenerative diseases, neuropsychiatric and mood disorders, and cancer,
      including gliomas.

PMID- 22879060
TI  - The role of the central nervous system in osteoarthritis pain and implications
      for rehabilitation.
AB  - It has been known for some time that central nervous system (CNS) pain
      amplification is present in some individuals with osteoarthritis; the
      implications of this involvement, however, are just starting to be realized. In
      the past year, several research reviews have focused on evidence supporting
      shared mechanisms across chronic pain conditions for how pain is generated and
      maintained in the CNS, irrespective of the underlying structural pathology. This
      review article focuses on current literature describing CNS amplification in
      osteoarthritis by discussing peripheral sensitization, central sensitization, and
      central augmentation, and the clinical manifestation of central augmentation
      referred to as centralized pain, and offers considerations for rehabilitation
      treatment and future directions for research.

PMID- 22879062
TI  - Adenosine signaling in glioma cells.
AB  - Purines and pyrimidines are fundamental signaling molecules in controlling the
      survival and proliferation of astrocytes, as well as in mediating cell-to-cell
      communication between glial cells and neurons in the healthy brain. The malignant
      transformation of astrocytes towards progressively more aggressive brain tumors
      (from astrocytoma to anaplastic glioblastoma) leads to modifications in both the
      survival and cell death pathways which overall confer a growth advantage to
      malignant cells and resistance to many cytotoxic stimuli. It has been
      demonstrated, however, that, in astrocytomas, several purinergic (in particular
      adenosinergic) pathways controlling cell survival and death are still effective
      and, in some cases, even enhanced, providing invaluable targets for purine-based
      chemotherapy, that still represents an appropriate pharmacological approach to
      brain tumors. In this chapter, the current knowledge on both receptor-mediated
      and receptor-independent adenosine pathways in astrocytomas will be reviewed,
      with a particular emphasis on the most promising targets which could be
      translated from in vitro studies to in vivo pharmacology.

PMID- 22879063
TI  - Cross-talk in nucleotide signaling in glioma C6 cells.
AB  - The chapter is focused on the mechanism of action of metabotropic P2Y nucleotide
      receptors: P2Y(1), P2Y(2), P2Y(12), P2Y(14) and the ionotropic P2X(7) receptor in
      glioma C6 cells. P2Y(1) and P2Y(12) both respond to ADP, but while P2Y(1) links
      to PLC and elevates cytosolic Ca(2+) concentration, P2Y(12) negatively couples to
      adenylate cyclase, maintaining cAMP at low level. In glioma C6, these two P2Y
      receptors modulate activities of ERK1/2 and PI3K/Akt signaling and the effects
      depend on physiological conditions of the cells. During prolonged serum
      deprivation, cell growth is arrested, the expression of the P2Y(1) receptor
      strongly decreases and P2Y(12) becomes a major player responsible for ADP-evoked
      signal transduction. The P2Y(12) receptor activates ERK1/2 kinase phosphorylation
      (a known cell proliferation regulator) and stimulates Akt activity, contributing
      to glioma invasiveness. In contrast, P2Y(1) has an inhibitory effect on Akt
      pathway signaling. Furthermore, the P2X(7) receptor, often responsible for
      apoptotic fate, is not involved in Ca(2+)elevation in C6 cells. The shift in
      nucleotide receptor expression from P2Y(1) to P2Y(12) during serum withdrawal,
      the cross talk between both receptors and the lack of P2X(7) activity shows the
      precise self-regulating mechanism, enhancing survival and preserving the
      neoplastic features of C6 cells.

PMID- 22879064
TI  - Calcium signaling in glioma cells--the role of nucleotide receptors.
AB  - Calcium signaling is probably one of the evolutionary oldest and the most common
      way by which the signal can be transmitted from the cell environment to the
      cytoplasmic calcium binding effectors. Calcium signal is fast and due to
      diversity of calcium binding proteins it may have a very broad effect on cell
      behavior. Being a crucial player in neuronal transmission it is also very
      important for glia physiology. It is responsible for the cross-talk between
      neurons and astrocytes, for microglia activation and motility. Changes in calcium
      signaling are also crucial for the behavior of transformed glioma cells. The
      present Chapter summarizes molecular mechanisms of calcium signal formation
      present in glial cells with a strong emphasis on extracellular nucleotide-evoked
      signaling pathways. Some aspects of glioma C6 signaling such as the cross-talk
      between P2Y(1) and P2Y(12) nucleotide receptors in calcium signal generation will
      be discussed in-depth, to show complexity of machinery engaged in formation of
      this signal. Moreover, possible mechanisms of modulation of the calcium signal in
      diverse environments there will be presented herein. Finally, the possible role
      of calcium signal in glioma motility is also discussed. This is a very important
      issue, since glioma cells, contrary to the vast majority of neoplastic cells,
      cannot spread in the body with the bloodstream and, at least in early stages of
      tumor development, may expand only by means of sheer motility.

PMID- 22879065
TI  - Purinergic signaling in glioma progression.
AB  - Among the pathological alterations that give tumor cells invasive potential,
      purinergic signaling is emerging as an important component. Studies performed in
      in vitro, in vivo and ex vivo glioma models indicate that alterations in the
      purinergic signaling are involved in the progression of these tumors. Gliomas
      have low expression of all E-NTPDases, when compared to astrocytes in culture.
      Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic,
      does not evoke cytotoxic action on the majority of glioma cells in culture. The
      importance of extracellular ATP for glioma pathobiology was confirmed by the
      reduction in glioma tumor size by apyrase, which degrades extracellular ATP to
      AMP, and the striking increase in tumor size by over-expression of an ecto-enzyme
      that degrades ATP to ADP, suggesting the effect of extracellular ATP on the tumor
      growth depends on the nucleotide produced by its degradation. The participation
      of purinergic receptors on glioma progression, particularly P2X(7), is involved
      in the resistance to ATP-induced cell death. Although more studies are necessary,
      the purinergic signaling, including ectonucleotidases and receptors, may be
      considered as future target for glioma pharmacological or gene therapy.

PMID- 22879066
TI  - Cytoskeleton and nucleotide signaling in glioma C6 cells.
AB  - This chapter describes signaling pathways stimulated by the P2Y(2) nucleotide
      receptor (P2Y(2)R), that regulate cellular processes dependent on actin
      cytoskeleton dynamics in glioma C6 cells. P2Y(2)R coupled with G-proteins, in
      response to ATP or UTP, regulates the level of phosphatidylinositol-4,5
      bisphosphate (PIP(2)) which modulates a variety of actin binding proteins and is
      involved in calcium response and activates Rac1 and RhoA proteins. The RhoA/ROCK
      signaling pathway plays an important role in contractile force generation needed
      for the assembly of stress fibers, focal adhesions and for tail retraction during
      cell migration. Blocking of this pathway by a specific Rho-kinase inhibitor
      induces changes in F-actin organization and cell shape and decreases the level of
      phosphorylated myosin II and cofilin. In glioma C6 cells these changes are
      reversed after UTP stimulation of P2Y(2)R. Signaling pathways responsible for
      this compensation are connected with calcium signaling. Stimulation of the Rac1
      mediated pathway via G(o) proteins needs additional interaction between
      alpha(v)beta(5) integrins and P2Y(2)Rs. Rac1 activation is necessary for cofilin
      phosphorylation as well as integrin activation needed for focal complexes
      formation and stabilization of lamellipodium. Inhibition of positive Rac1
      regulation prevents glioma C6 cells from recovery of control cell like
      morphology.

PMID- 22879067
TI  - Signaling determinants of glioma cell invasion.
AB  - Tumor cell invasiveness is a critical challenge in the clinical management of
      glioma patients. In addition, there is accumulating evidence that current
      therapeutic modalities, including anti-angiogenic therapy and radiotherapy, can
      enhance glioma invasiveness. Glioma cell invasion is stimulated by both autocrine
      and paracrine factors that act on a large array of cell surface-bound receptors.
      Key signaling elements that mediate receptor-initiated signaling in the
      regulation of glioblastoma invasion are Rho family GTPases, including Rac, RhoA
      and Cdc42. These GTPases regulate cell morphology and actin dynamics and
      stimulate cell squeezing through the narrow extracellular spaces that are typical
      of the brain parenchyma. Transient attachment of cells to the extracellular
      matrix is also necessary for glioblastoma cell invasion. Interactions with
      extracellular matrix components are mediated by integrins that initiate diverse
      intracellular signalling pathways. Key signaling elements stimulated by integrins
      include PI3K, Akt, mTOR and MAP kinases. In order to detach from the tumor mass,
      glioma cells secrete proteolytic enzymes that cleave cell surface adhesion
      molecules, including CD44 and L1. Key proteases produced by glioma cells include
      uPA, ADAMs and MMPs. Increased understanding of the molecular mechanisms that
      control glioma cell invasion has led to the identification of molecular targets
      for therapeutic intervention in this devastating disease.

PMID- 22879068
TI  - Receptor tyrosine kinases: principles and functions in glioma invasion.
AB  - Protein tyrosine kinases are enzymes that are capable of adding a phosphate group
      to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a
      tyrosine kinase located at the cellular membrane and is activated by binding of a
      ligand via its extracellular domain. Protein phosphorylation by kinases is an
      important mechanism for communicating signals within a cell and regulating
      cellular activity; furthermore, this mechanism functions as an "on" or "off"
      switch in many cellular functions. Ninety unique tyrosine kinase genes, including
      58 RTKs, were identified in the human genome; the products of these genes
      regulate cellular proliferation, survival, differentiation, function, and
      motility. Tyrosine kinases play a critical role in the development and
      progression of many types of cancer, in addition to their roles as key regulators
      of normal cellular processes. Recent studies have revealed that RTKs such as
      epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor
      (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin
      producing human hepatocellular carcinoma (Eph) play a major role in glioma
      invasion. Herein, we summarize recent advances in understanding the role of RTKs
      in glioma pathobiology, especially the invasive phenotype, and present the
      perspective that RTKs are a potential target of glioma therapy.

PMID- 22879069
TI  - TGF beta signaling and its role in glioma pathogenesis.
AB  - Transforming growth factor beta (TGF-beta) signaling is involved in the
      regulation of proliferation, differentiation and survival/or apoptosis of many
      cells, including glioma cells. TGF-beta acts via specific receptors activating
      multiple intracellular pathways resulting in phosphorylation of receptor
      regulated Smad2/3 proteins that associate with the common mediator, Smad4. Such
      complex translocates to the nucleus, binds to DNA and regulates transcription of
      many genes. Furthermore, TGF-beta-activated kinase-1 (TAK1) is a component of TGF
      beta signaling and activates mitogen-activated protein kinase cascades. Negative
      regulation of TGF-beta/Smad signaling may occur through the inhibitory Smad6/7.
      Increased expression of TGF-beta1-3 correlates with a degree of malignancy of
      human gliomas. TGF-beta may contribute to tumor pathogenesis by direct support of
      tumor growth, self-renewal of glioma initiating stem cells and inhibiting of anti
      tumor immunity. TGF-beta1,2 stimulate expression of the vascular endothelial
      growth factor as well as the plasminogen activator inhibitor and some
      metalloproteinases that are involved in vascular remodeling, angiogenesis and
      degradation of the extracellular matrix. Inhibitors of TGF-beta signaling reduce
      viability and invasion of gliomas in animal models and show promises as novel,
      potential anti-tumor therapeutics.

PMID- 22879070
TI  - STAT signaling in glioma cells.
AB  - STAT (signal transducers and activators of transcription) are latent cytoplasmic
      transcription factors that function as downstream effectors of cytokine and
      growth factor receptor signaling. The canonical JAK/STAT signaling pathway
      involves the activation of Janus kinases (JAK) or growth factors receptor
      kinases, phosphorylation of STAT proteins, their dimerization and translocation
      into the nucleus where STATs act as transcription factors with pleiotropic
      downstream effects. STAT signaling is tightly controlled with restricted kinetics
      due to action of its negative regulators. While STAT1 is believed to play an
      important role in growth arrest and apoptosis, and to act as a tumor suppressor,
      STAT3 and 5 are involved in promoting cell cycle progression, cellular
      transformation, and preventing apoptosis. Aberrant activation of STATs, in
      particular STAT3 and STAT5, have been found in a large number of human tumors,
      including gliomas and may contribute to oncogenesis. In this chapter, we have (1)
      summarized the mechanisms of STAT activation in normal and malignant signaling;
      (2) discussed evidence for the critical role of constitutively activated STAT3
      and STAT5 in glioma pathobiology; (3) disclosed molecular and pharmacological
      strategies to interfere with STAT signaling for potential therapeutic
      intervention in gliomas.

PMID- 22879071
TI  - Cannabinoid signaling in glioma cells.
AB  - Cannabinoids are a group of structurally heterogeneous but pharmacologically
      related compounds, including plant-derived cannabinoids, synthetic substances and
      endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol.
      Cannabinoids elicit a wide range of central and peripheral effects mostly
      mediated through cannabinoid receptors. There are two types of specific G(i/o)
      protein-coupled receptors cloned so far, called CB1 and CB2, although an
      existence of additional cannabinoid-binding receptors has been suggested. CB1 and
      CB2 differ in their predicted amino acid sequence, tissue distribution,
      physiological role and signaling mechanisms. Significant alterations of a balance
      in the cannabinoid system between the levels of endogenous ligands and their
      receptors occur during malignant transformation in various types of cancer,
      including gliomas. Cannabinoids exert anti-proliferative action in tumor cells.
      Induction of cell death by cannabinoid treatment relies on the generation of a
      pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial
      for regulation of cellular proliferation, differentiation or apoptosis. Increased
      ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma
      cells.

PMID- 22879072
TI  - When are urodynamics indicated in patients with stress urinary incontinence?
AB  - Despite technical and procedural advances in urodynamics over the past decade,
      the role of urodynamics in women with stress urinary incontinence (SUI) remains
      controversial. Many of these advancements have been the result of multicentric
      studies in the United States, such as the UITN and PFDN, which will be
      highlighted in this article. It appears to be the consensus that urodynamics may
      not be needed in pure stress incontinence. Urodynamics can be valuable in
      unmasking stress urinary incontinence in prolapse, although its impact on the
      ultimate management of occult incontinence remains debated. This article reviews
      the indications for urodynamic testing in women with SUI but will exclude more
      complex conditions such as mixed or recurrent incontinence which are outside the
      scope of this review.

PMID- 22879073
TI  - Neurogenesis and hippocampal plasticity in adult brain.
AB  - Plasticity in the adult brain enables lifelong learning. The fundamental
      mechanism of adult neural plasticity is activity-dependent reorganization of pre
      existing structure, in contrast to the widespread cellular proliferation and
      migration that occurs during development. Whereas adult hippocampal dentate gyrus
      continuously generates cohorts of neurons, and newborn neurons integrate into the
      existing neural circuit under the regulation of existing global and local neural
      activity, demonstrating a unique cellular and synaptic flexibility in adult
      brain. Exhibiting an enhanced structural and synaptic plasticity during the
      maturation, adult-born hippocampal neurons may represent a unique population for
      hippocampal function. Current evidence indicates that lifelong addition of new
      hippocampal neurons may extend early developmental plasticity to adulthood, which
      continuously rejuvenates adult brain. We reviewed most recent advancements in
      exploring the circuit and behavioral role of adult-born hippocampal neurons.

PMID- 22879074
TI  - Ethical research on the implementation of DRGs in Switzerland--a challenging
      project.
AB  - Diagnosis Related Groups (DRGs) are currently being introduced on a national
      scale as a prospective reimbursement scheme in Swiss in-patient hospital care,
      replacing any remaining retrospective day-rate arrangements. DRGs are expected to
      promote transparency and efficiency while helping to contain health care costs.
      The governmental decision to introduce DRGs has caused considerable controversy
      among different stakeholders, due to diverging appraisals of what will happen
      when DRGs are introduced as an economic management tool in Switzerland. The
      controversial discourse on DRGs is particularly interesting from an ethical point
      of view, since all arguments inevitably contain ethical considerations. In this
      paper we summarise the results of our exploratory ethical studies that have led
      to a larger research project funded by the Swiss National Science Foundation:
      "Impact of Diagnosis-Related Groups (DRGs) on patient care and professional
      practice" (IDoC). In section 1: 'Developing an understanding of the ethical
      issues at stake' we briefly explain how DRGs work, what the intended effects are,
      what the public is concerned about and what the scientific research tells us so
      far. In section 2: 'Developing an ethical framework for research on DRGs in
      Switzerland' we summarise the ethical issues and explain the ethical framework we
      will use in order to perform research on the complex issue of DRGs in
      Switzerland. Only once a profound understanding of the challenges exists can
      research on the ethical implications of DRGs be successful.

PMID- 22879076
TI  - Abnormal glucose and lipid control in non-ischemic left ventricular dysfunction.
AB  - BACKGROUND: Cardiovascular risk factors are classically associated with coronary
      atherosclerosis. We sought to investigate whether risk factors are also
      associated with left ventricular (LV) dilatation, contractile impairment and
      reduced myocardial blood flow (MBF) in patients with non-ischemic LV dysfunction.
      METHODS: We studied 81 patients (59 males, age 60 +/- 9 years) with mild-to
      severe LV dysfunction (mean ejection fraction 37%, range 19%-50%), no history of
      diabetes and normal coronary arteries. Absolute MBF was measured by positron
      emission tomography and (13)N-ammonia at rest and after dipyridamole (0.56 mg/kg
      I.V. over 4 min). RESULTS: Overt LV dysfunction (LV end-diastolic diameter >60 mm
      associated with LV ejection fraction <45%) was present in 42 patients (52%);
      severely depressed hyperemic MBF (<1.09 mL . min(-1) . g(-1)) was present in 41
      patients (51%). Using multivariate logistic regression analysis, low high-density
      lipoprotein cholesterol (HDL-C, P < .036), newly diagnosed non-insulin-dependent
      diabetes or insulin-resistance (NIDD/IR, P < .019) and the use of diuretics (P =
      .001) were independently associated with overt LV dysfunction. Low HDL-C (P =
      .015) and NIDD/IR (P = .048) were also independently associated with severely
      depressed hyperemic MBF. CONCLUSIONS: Low HDL-C and NIDD/IR are associated with
      more severe LV impairment and reduced hyperemic MBF in non-ischemic LV
      dysfunction.

PMID- 22879077
TI  - Neurodegenerative Disease and REM Behavior Disorder.
AB  - OPINION STATEMENT: Patients with cerebral degenerative conditions commonly suffer
      from a variety of sleep disorders, including sleep-disordered breathing,
      insomnia, parasomnias (REM sleep behavior disorder), circadian rhythm
      disturbances, and restless legs syndrome. When these sleep disorders go
      unrecognized and untreated, they can lead to decreased quality of life and
      worsening neurological symptoms related to the underlying condition. Appropriate
      management initially requires taking a careful history from the patient and bed
      partner regarding their sleep. In addition, polysomnography may be required to
      aid in the diagnosis of sleep-disordered breathing or parasomnias. Occasionally,
      adjusting the dosages of sedating or sleep disrupting medications and improving
      sleep hygiene may improve sleep complaints. However, in most cases restoring
      quality nighttime sleep requires specific therapeutic intervention. In patients
      that suffer from sleep apnea, this usually means treatment with continuous
      positive airway pressure (CPAP), positional therapy, dental appliances, upper
      airway surgery, or weight loss. Pharmacological treatment of insomnia in patients
      with cerebral degenerative conditions can be difficult due to side effects
      (worsening balance, cognition) and lack of data in this patient population.
      Behavioral strategies such as cognitive-behavioral therapy have been effective
      and are considered safer than hypnotic therapy, but can be limited due to access
      to trained providers (distance and number of providers) and limited cognitive
      functioning of the patient. Parasomnias, namely REM sleep behavior disorder, are
      managed by looking for any underlying cause of arousals (sleep apnea, periodic
      leg movements of sleep), implementing safety precautions, and pharmacologically
      with either benzodiazepines or melatonin. Restless legs syndrome may improve with
      iron replacement or dopamine agonist therapy, as it does in other patient
      populations. Light therapy may be beneficial in patients suffering from circadian
      rhythm disorders such as advanced sleep phase syndrome.

PMID- 22879078
TI  - PET of signal transduction pathways in cancer.
AB  - In this era of systems biology, the tide of information derived from "omic"
      technologies (genomics, proteomics, etc.) has sparked a revolution in drug
      design, with many industrial and academic programs now embracing the concepts of
      molecular medicine (i.e., targeting changes in specific proteins or pathways) as
      measures of treatment efficacy and outcome. This approach has yielded a plethora
      of new preclinical therapeutics directed at novel targets within oncology. In
      many ways, the evolution of molecular imaging agents as diagnostic probes mirrors
      that of chemotherapeutics; yet despite an increasing number of PET and SPECT
      radiotracers being evaluated in human trials, relatively few agents have found
      widespread use in clinical oncology. In light of this observation, is it time to
      reevaluate our strategies for radiopharmaceutical design and use? In this
      article, we argue that PET has enormous potential to deliver clinically relevant
      information on disease dynamics that extends beyond mapping the density and
      spatial distribution of a target. Recent developments in targeting
      pharmacodynamic biomarkers aim to exploit better the advantages of functional PET
      by detecting changes in signal transduction pathways, particularly in response to
      disease progression or treatment in cancer.

PMID- 22879079
TI  - Workflow and scan protocol considerations for integrated whole-body PET/MRI in
      oncology.
AB  - Integrated PET/MRI systems open exciting possibilities for clinical and research
      applications. However, compared with PET/CT, PET/MRI is a complex technique
      resulting in new problems and challenges, especially regarding workflow, scan
      protocols, and data analysis. This complexity applies in particular to
      examinations in oncology with partial- or whole-body coverage extending over
      several bed positions. Unlike diagnostic PET/CT, for which the clinical CT
      protocols can largely be copied from stand-alone CT, the design of a diagnostic
      MRI protocol for partial- or whole-body coverage is more complex and has to be
      adapted to the special requirements of PET/MRI to be both time-efficient and
      comprehensive. Here, we describe basic considerations concerning workflow,
      imaging protocols, and image analysis for whole-body PET/MRI in oncology, based
      on our experience with the first integrated PET/MRI scanner. The aim is to fully
      and optimally make use of the combined PET/MRI measurements in oncology,
      including identifying and reducing image artifacts as well as optimizing workflow
      beyond the mere fusion of 2 image datasets.

PMID- 22879080
TI  - The utility of 18F-FDG PET/CT for diagnosis and adjustment of therapy in patients
      with active chronic sarcoidosis.
AB  - The purpose of this study was to assess the utility of (18)F-FDG PET/CT for
      detection of inflammation in granulomatous sites and management of patients with
      chronic sarcoidosis. The 3 specific aims were to assess differences between (18)F
      FDG PET/CT and multidetector CT (MDCT) findings, to compare (18)F-FDG PET/CT
      results with serum levels of angiotensin-converting enzyme (ACE), and to
      determine whether (18)F-FDG PET/CT findings are associated with the decision to
      change therapy. METHODS: We studied 90 sarcoidosis patients (mean age +/- SD, 47
      +/- 12 y; 32 men and 58 women) with persistent symptoms who were referred for
      (18)F-FDG PET/CT evaluation to assess the extent of inflammation. They also
      underwent MDCT and measurement of serum ACE level. After the follow-up (12 +/- 5
      mo after (18)F-FDG PET/CT), the clinical status and changes in therapy were
      analyzed. RESULTS: (18)F-FDG PET/CT detected inflammation in 74 patients (82%)
      (maximum standardized uptake value, 8.1 +/- 3.9). MDCT was positive for
      sarcoidosis in 6 additional patients (80, 89%). The difference between the 2
      methods was not significant (P = 0.238, McNemar test), and their agreement was
      fair (kappa = 0.198). Although ACE levels were significantly higher in patients
      with positive than negative (18)F-FDG PET/CT results (P = 0.002, Mann-Whitney
      test), 38 patients (51%) with positive (18)F-FDG PET/CT results had normal ACE
      levels. The therapy was initiated or changed in 73 out of 90 patients (81%). Both
      univariate and multivariate logistic regression analyses indicated that positive
      (18)F-FDG PET/CT results were significantly (P < 0.001) associated with changes
      in therapy, with no contribution from age, sex, ACE level, CT results, or
      previous therapy. CONCLUSION: Our results indicate that (18)F-FDG PET/CT is a
      useful adjunct to other diagnostic methods for detecting active inflammatory
      sites in chronic sarcoidosis patients with persistent symptoms, especially those
      with normal ACE levels. (18)F-FDG PET/CT proved advantageous for determining the
      spread of active disease throughout the body and influenced the decision to
      adjust the therapy.

PMID- 22879082
TI  - Widespread watershed infarct in patient with malignancy-related hypercoagulation.

PMID- 22879083
TI  - The clinical relevance of vertebral artery hypoplasia.
AB  - Congenital vertebral artery (VA) hypoplasia is an uncommon embryonic variation of
      posterior circulation. The frequency of this congenital variation was reported to
      be 2-6% from autopsy and angiograms. Is it a congenital risk factor of ischemic
      stroke? In this review, we gave an overview of the literature concerning
      vertebral artery hypoplasia. VA hypoplasia served as an independent factor of a
      reduction of the posterior circulation blood flow velocity. VA hypoplasia can
      play a negative role in cases of occlusion of a major brain vessel since it
      limits the potential of compensatory blood circulation. VA hypoplasia may also
      lead to regional hypoperfusion and complex neurovascular consequences which
      correspond to vestibular neuronitis and migraine pathogenesis.

PMID- 22879081
TI  - Response assessment using 18F-FDG PET early in the course of radiotherapy
      correlates with survival in advanced-stage non-small cell lung cancer.
AB  - This study investigated the possibility of early response assessment based on
      (18)F-FDG uptake during radiotherapy with respect to overall survival in patients
      with non-small cell lung cancer. METHODS: (18)F-FDG PET/CT was performed before
      radiotherapy and was repeated in the second week of radiotherapy for 34
      consecutive lung cancer patients. The CT volume and standardized uptake value
      (SUV) parameters of the primary tumor were quantified at both time points.
      Changes in volume and SUV parameters correlated with 2-y overall survival.
      RESULTS: The average change in mean SUV in the primary tumor of patients with a 2
      y survival was a decrease by 20% +/- 21%-significantly different (P < 0.007) from
      nonsurvivors, who had an increase by 2% +/- 22%. A sensitivity and specificity of
      63% and 93%, respectively, to separate the 2 groups was reached for a decrease in
      mean SUV of 15%. Survival curves were significantly different using this cutoff
      (P = 0.001). The hazard ratio for a 1% decrease in mean SUV was 1.032 (95%
      confidence interval, 1.010-1.055). Changes in tumor volume defined on CT did not
      correlate with overall survival. CONCLUSION: The use of repeated (18)F-FDG PET to
      assess treatment response early during radiotherapy is possible in patients
      undergoing radiotherapy or sequential or concurrent chemoradiotherapy. A decrease
      in (18)F-FDG uptake by the primary tumor correlates with higher long-term overall
      survival.

PMID- 22879084
TI  - Neuro-psychological sequelae in HIV-negative cryptococcal meningitis after
      complete anti-fungal treatment.
AB  - PURPOSES: The cognitive sequelae and influence of depression in patients with
      cryptococcal meningitis (CM) after complete anti-fungal treatment has not been
      completely surveyed in literature. METHODS: Seventeen HIV-negative CM patients
      and 26 health y controls were enrolled in this prospective study. Neuro
      psychological evaluation was performed to assess the attention, execution, speech
      and language, semantic and visuo-construction function, and depression. These
      were correlated with longitudinal magnetic resonance imaging (MRI) through the
      following checklists: dilated Virchow-Robin spaces, pseudo-cysts, intra-cerebral
      nodule or mass, meningeal enhancement, hydrocephalus, and hyper-intensity of
      white matter. For cognitive outcome measurement, initial clinical and biochemical
      markers were collected and analyzed. RESULTS: The mean follow-up duration in CM
      patients was 69.6 months. They had impairments in attention, execution, speech
      and language, and visuo-construction function, while six (35%) patients fulfilled
      the depression criteria. Initial cryptococcal antigen titer was inversely
      correlated with block design score (rho=-0.54, p<0.05), after adjustment for
      depression. Patients with two or more CM-related lesions (mean, 19.2; SD, 12.6)
      (p=0.04). CM with depression is highly associated with poor cognitive performance
      and higher likelihood of two or more lesions in MRI (likelihood ratio=6.012,
      p=0.014). CONCLUSION: Cognitive deficits persist in CM patients even after
      complete treatment. The number of lesions plays an important role in cognitive
      performance and depression. Extensive involvement of the cognitive domains with
      wide radiographic presentations suggests a disseminated nature of cryptococcus.

PMID- 22879085
TI  - The association of metabolic risk factors and silent brain infarctions in healthy
      Taiwanese.
AB  - PURPOSE: Silent brain infarctions (SBI) commonly go unnoticed due to the subtlety
      of their neurological signs. However, there is the risk of subsequent symptomatic
      stroke and dementia. A better understanding of the risk factors of SBI may help
      accurately predict those who will require treatment. METHODS: This one-year
      retrospective study enrolled 199 adult healthy Taiwanese. Multiple logistic
      regression analysis was used to evaluate the relationships between baseline
      clinical factors and the presence of SBI during the study period. RESULTS:
      Fifteen (7.5%) healthy subjects had SBI, including 4.9% (5/103) males and 10.4%
      (10/96) females. Multiple logistic regression analysis revealed that both mean
      age and hypertension were independently associated with SBI, such that any
      increase of one year in mean age increased the SBI rate by 7.3%. CONCLUSION: In
      the present study, there is a close relationship between elderly patients and SBI
      and any increase of one year in mean age increases the SBI rate by 7.3%. Aside
      from age, hypertension is by far the strongest modifiable risk factor identified
      to date. Prospective, longitudinal observational studies are warranted to
      evaluate the relationship between control of hypertension and SBI in this
      specific population to determine how to prevent subsequent symptomatic stroke.

PMID- 22879086
TI  - A potential protective effect in multilingual patients with semantic dementia:
      two case reports of patients speaking Taiwanese and Japanese.
AB  - PURPOSE: Several reports have suggested that multilingualism has a protective
      effect against semantic dementia. Here, we provide further evidence for this
      effect. CASE REPORTS FIRST: The patient was a 75-year-old right-handed Taiwanese
      woman who had retired after working as a tailor. She was able to speak Taiwanese,
      Japanese and Mandarin Chinese fluently until 5 years ago. She gradually developed
      symptoms of profound anomia and difficulty with word-finding. Her mother tongue
      was Taiwanese and she had learned Japanese as her first symbolized language. She
      had used Mandarin Chinese for most of her life, but depended on Japanese to read
      and write (such as reading a newspaper and keeping accounts). However, she could
      now speak only very simple Taiwanese and Japanese, and could recognize only
      simple Japanese characters. SECOND: The patient was a 62-year-old right-handed
      man who had worked as an ironworker. He could speak Taiwanese and Mandarin
      Chinese fluently until 5 years ago. His mother tongue was Taiwanese. After 5
      years of language deterioration, he was unable to communicate with his family
      members or recognize any characters, including numbers. SPECT RESULTS: Brain
      perfusion ECD SPECT (Tc-99m-ethyl cysteinate dimer single-photon emission
      computed tomography) showed less perfusion in the multilingual patient (Case #1)
      than in the bilingual patient (Case #2). Neuropsychological tests also
      demonstrated a slower rate of degeneration in the multilingual patient.
      CONCLUSION: We speculate that reading and writing in Japanese had a greater
      impact on the semantic system in Case #1. Thus, this patient showed relatively
      less degeneration or functional inactivity, as shown by perfusion in the frontal
      lobe, and this might be due to the persistent activation involved in
      multilingualism.

PMID- 22879087
TI  - Spontaneous spinal epidural hematoma: a case report and review of the
      literatures.
AB  - PURPOSE: To emphasize the importance of early recognition and emergent surgery
      for spontaneous spinal epidural hematoma (SSEH). CASE REPORT: A 61-year-old
      female presented with sudden onset of severe neck and back pain after finishing
      worshiping Buddha followed by quadriparesis, sensory deficits below C4 level and
      sphincter dysfunction. MR imaging demonstrated acute extensive epidural hematoma
      of cervico-thoracic spinal segments (C2-T7). Idiopathic SSEH was diagnosed and
      emergent decompressive laminectomy with hematoma evacuation was performed within
      12 hours of symptoms onset. Good functional and neurological outcomes were
      obtained. CONCLUSION: SSEH is a rare but disabling or even fatal entity. Early
      diagnosis and prompt surgery improve the neurological and functional outcome but
      still remain a clinical challenge. Relevant physicians should pay attention to
      the typical symptoms of the rare entity and SSEH should be one of differential
      diagnoses.

PMID- 22879088
TI  - Reverse Lhermitte's phenomenon provoked by cervical cord compression.
AB  - PURPOSE: Lhermitte's phenomenon (LP) is a rare manifestation, which is defined
      when a sudden electric-shock sensation transmitted down the spine induced by neck
      flexion; however, the reverse LP is defined when symptoms are induced by neck
      extension, not flexion. Because reports of LP are limited in the Taiwan
      literature, we report this case. CASE REPORT: A 74-year-old woman presented to
      our emergency department with sudden onset of right neck pain when extending the
      neck. The pain mimicked an electric shock and radiated to the left shoulder.
      Imaging showed spondylosis and spondylolisthesis without any spinal canal
      stenosis. A neck collar was recommended, and the strange phenomenon did not recur
      over the following year. However, long-term follow-up and aggressive workup are
      recommended to rule in or rule out the possibility of multiple sclerosis in the
      future. CONCLUSION: Although LP represents spinal demyelination disorders,
      reverse LP is induced by extrinsic compression of the cervical cord, and neck
      collar immobilization rather than intravenous or oral medication is recommended.

PMID- 22879089
TI  - Heavy binge drinking may increase risk of stroke in nonalcoholic hypertensives
      carrying variant ALDH2*2 gene allele.
AB  - PURPOSE: Epidemiologic evidence demonstrates that heavy drinking increases the
      risk of stroke. However, whether recent heavy drinking affects the incidence of
      acute stroke in nonalcoholic individuals with the variant allele ALDH2*2 has not
      been reported. CASE REPORT: Two previously nonalcoholic healthy men suffered from
      acute ischemic stroke after a single episode of binge drinking. Both patients had
      one risk factor for stroke (a history of hypertension) and were heterozygous for
      ALDH2*2. CONCULUSION: The confluence of these factors with stroke has raised the
      possibility that heavy binge drinking increases the risk of acute stroke in
      hypertensives with the variant ALDH2*2 gene allele.

PMID- 22879090
TI  - Pallidoreticular lesion in carbon monoxide intoxication by gradient echo: report
      of a case with parkinsonism features and review of the literature.
AB  - PURPOSE: Pallidoreticular damage was defined by lesions involving both the
      pallidum and the substantia nigra and was only reported in four cases after CO
      intoxication. CASE REPORT: We report a patient with initial consciousness
      disturbances followed by parkinsonian features after carbon monoxide
      intoxication. The unique features in this patient included primary globus
      pallidus hemorrhage followed by delayed hemorrhage in pallidoreticular topography
      demonstrated by T1- and T2-weighted imaging. In the follow-up study 7 months
      later, the patient still presented with parkinsonism features and executive
      dysfunction while the pallidoreticular signal was only visible by gradient echo
      sequences but not the other MR conventional sequences. Hypometabolism in the
      frontal and basal ganglion regions were evident from 99mTc-TRODAT-1 study and
      partial responsiveness to levodopa in alleviating parkinsonian features was
      considered. CONCLUSION: This case highlights the delayed development of
      pallidoreticular damages and its linkage in modulating prefrontal-subcortical
      neuronal circuits.

PMID- 22879091
TI  - Is posterior hip instability associated with cam and pincer deformity?
AB  - BACKGROUND: Posterior hip instability is an increasingly recognized injury in
      athletes; however, the function of patients after these injuries and an
      understanding of the pathoanatomy and underlying mechanism are currently unclear.
      QUESTIONS/PURPOSES: We determined (1) the function of patients after these hip
      injuries using validated, self-reported outcome instruments and (2) the specific
      pathoanatomy sustained in these events to better understand the mechanism of
      posterior hip instability. METHODS: We reviewed the records of all 22 athletes
      presenting to our clinics with a posterior acetabular rim fracture confirming a
      posterior hip instability episode. Radiograph, CT, and MRI findings were
      documented in all patients. Intraoperative findings were recorded in patients
      undergoing surgery. There were 19 males and three females with an average age of
      22 years (range, 13-31 years). Minimum followup was 2 years (average, 4 years;
      range, 2-16 years). RESULTS: The mean modified Harris hip score was 94, Hip
      Outcome Scores for Activities of Daily Living and Sport were 99 and 87,
      respectively, and 20 of 22 athletes returned to sport. The most common
      constellation of pathoanatomy was a posterior labral tear with rim fracture,
      anterior labral tear, capsular tear, ligamentum teres avulsion, and chondral
      injury of the femoral head with loose bodies. Sixteen of the 18 patients with
      femoroacetabular impingement (FAI) had a twisting or noncontact mechanism of
      injury. CONCLUSIONS: When posterior hip subluxation is recognized and avascular
      necrosis avoided, these athletes generally have high functional outcome scores
      and high rates of return to sport. There is an apparent association between the
      occurrence of posterior hip instability and the presence of structural
      abnormalities often associated with FAI, which may contribute to a mechanism of
      FAI-induced posterior subluxation. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22879092
TI  - Can microcomputed tomography measure retrieved polyethylene wear? Comparing fixed
      bearing and rotating-platform knees.
AB  - BACKGROUND: Wear of total knee polyethylene has been quantified gravimetrically
      with thickness measurements and evaluation of surface wear modes. However, these
      techniques do not localize volumetric wear. QUESTIONS/PURPOSES: We used micro-CT
      scans of retrieved total knee liners and unworn, new liners to determine the
      volume and location of wear. METHODS: We retrieved 12 fixed and 12 rotating
      platform bearings after a mean 52 months of use. Inserts were weighed and
      thickness was measured. Micro-CT scans of retrieved and matched new liners were
      superimposed to compare the location and magnitude of wear. RESULTS: The average
      total wear was 254 +/- 248 mm(3). The average wear rate was 58 +/- 41 mm(3)/year.
      Wear was 69% of penetration, demonstrating the contribution of deformation to
      knee wear. Rotating-platform wear rate was 43 +/- 25 mm(3)/year and the fixed
      bearing rate was 74 +/- 49 mm(3)/year. Five percent of the rotating-platform wear
      rate came from the backside compared with 14% of the fixed-bearing wear rate.
      CONCLUSIONS: Micro-CT can determine the volume and location of wear of retrieved
      tibial liners. Because the magnitude of the manufacturing tolerances was
      approximately half the magnitude of the total wear on average, accounting for the
      potential influence of tolerances is important to accurately measure volumetric
      wear if the unworn (preimplantation) geometry of the insert is unknown. Without
      accounting for tolerances, this technique may not be applicable for retrievals
      with a short followup that have low wear. However, application of micro-CT could
      be of value in determining the exact location of wear in knee simulator studies
      in which the same insert is measured repeatedly and manufacturing tolerances are
      not a concern.

PMID- 22879093
TI  - Orthopaedic case of the month: pulsatile soft tissue mass.

PMID- 22879094
TI  - White matter lesion progression in LADIS: frequency, clinical effects, and sample
      size calculations.
AB  - BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated
      as a surrogate marker in intervention trials on cerebral small vessel disease. We
      assessed the rate of visually rated WML progression, studied correlations between
      lesion progression and cognition, and estimated sample sizes for clinical trials
      with pure WML progression vs combined WML progression-cognitive outcomes.
      METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS)
      study with magnetic resonance imaging scanning at baseline and 3-year follow-up
      were analyzed. WML progression rating relied on the modified Rotterdam
      Progression Scale. The Vascular Dementia Assessment Scale global score and a
      composite score of specific executive function tests assessed longitudinal change
      in cognition. Sample size calculations were based on the assumption that
      treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale.
      RESULTS: WML progression related to deterioration in cognitive functioning. This
      relationship was less pronounced in subjects with early confluent and confluent
      lesions. Consequently, studies in which the outcome is cognitive change resulting
      from treatment effects on lesion progression will need between 1809 subjects per
      treatment arm when using executive tests and up to 18 853 subjects when using the
      Vascular Dementia Assessment Scale score. Studies having WML progression as the
      sole outcome will need only 58 or 70 individuals per treatment arm. CONCLUSIONS:
      WML progression is an interesting outcome for proof-of-concept studies in
      cerebral small vessel disease. If cognitive outcome measures are added to
      protocols, then sample size estimates increase substantially. Our data support
      the use of an executive test battery rather than the Vascular Dementia Assessment
      Scale as the primary cognitive outcome measure.

PMID- 22879096
TI  - Higher prehospital priority level of stroke improves thrombolysis frequency and
      time to stroke unit: the Hyper Acute STroke Alarm (HASTA) study.
AB  - BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances
      of a good recovery. This randomized controlled study evaluates how an increased
      priority level for patients with stroke, from level 2 to 1, from the Emergency
      Medical Communication Center influences thrombolysis frequency, time to stroke
      unit, and whether other medical emergencies reported negative consequences.
      METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of
      stroke within 6 hours were randomized from the Emergency Medical Communication
      Center or emergency medical services to an intervention group, priority level 1,
      immediate call of an ambulance, or to a control group with standard priority
      level, that is, priority level 2 (within 30 minutes). Before study start, an
      educational program on identification of stroke and importance of early initiated
      treatment was directed to all medical dispatchers and ambulance and emergency
      department personnel. RESULTS: During 2008, 942 patients were randomized of which
      53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in
      the Emergency Medical Communication Center randomized intervention group reached
      the stroke unit 26 minutes earlier than the control group (P<0.001) after the
      emergency call. Thrombolysis was given to 24% of the patients in the intervention
      group compared with 10% of the control subjects (P<0.001). The higher priority
      level showed no negative effect on other critical ill patients requiring priority
      level 1 prehospital attention. CONCLUSIONS: This randomized study shows
      negligible harm to other medical emergencies, a significant increase in
      thrombolysis frequency, and a shorter time to the stroke unit for patients with
      stroke upgraded to priority level 1 from the Emergency Medical Communication
      Center and through the acute chain of stroke care.

PMID- 22879095
TI  - Plasminogen activator inhibitor-1 and thrombotic cerebrovascular diseases.

PMID- 22879097
TI  - Cardiovascular disease risk and cerebral blood flow velocity.
AB  - BACKGROUND AND PURPOSE: Cardiovascular disease risk predicts cognitive decline
      although the mechanisms underpinning this association remain unclear. Increasing
      cardiovascular risk may impair cerebral blood flow predisposing to
      cerebrovascular damage, cognitive decline, and dementia. METHODS: This study
      examined the association between the Framingham General Cardiovascular Risk
      Profile and cerebral blood flow velocity in 160 healthy middle-aged adults. Blood
      flow velocity was assessed in both the common carotid and middle cerebral
      arteries using Doppler. RESULTS: In adjusted linear regression models,
      cardiovascular risk predicted higher pulsatile (common carotid artery beta=0.56,
      DeltaR(2)=0.19, P<0.001; middle cerebral artery beta=0.40, DeltaR(2)=0.09,
      P<0.001) and lower mean flow velocity (common carotid artery beta=-0.49,
      DeltaR(2)=0.14, P<0.001; middle cerebral artery beta=-0.27, DeltaR(2)=0.04,
      P<0.05). Cardiovascular risk predicted common carotid artery mean and pulsatile
      flow over and above the effects of age (DeltaR(2)=0.11-0.19, P<0.001) and sex
      (DeltaR(2)=0.03-0.03, P<0.05). In contrast, cardiovascular risk remained a
      significant predictor of middle cerebral artery pulsatile, but not mean flow
      velocity, when controlling for age (DeltaR(2)=0.05, P<0.05) and sex
      (DeltaR(2)=0.06, P<0.01). CONCLUSIONS: Cardiovascular risk has divergent effects
      on mean and pulsatile blood flow velocity, each of which may independently
      contribute to cerebral pathology and cognitive impairment.

PMID- 22879098
TI  - Memantine improves safety of thrombolysis for stroke.
AB  - BACKGROUND AND PURPOSE: Despite side effects including N-methyl-d-aspartate
      mediated neurotoxicity, recombinant tissue-type plasminogen activator (rtPA)
      remains the only approved acute treatment for ischemic stroke. Memantine, used
      for treatment of Alzheimer disease, is an antagonist for N-methyl-d-aspartate
      receptors. We investigated whether memantine could be used as a neuroprotective
      adjunct therapy for rtPA-induced thrombolysis after stroke. METHODS: In vitro N
      methyl-d-aspartate exposure, oxygen and glucose deprivation, and N-methyl-d
      aspartate-mediated calcium videomicroscopy experiments were performed on murine
      cortical neurons in the presence of rtPA and memantine. The therapeutic safety of
      rtPA and memantine coadministration was evaluated in mouse models of thrombotic
      stroke and intracerebral hemorrhage. Ischemic and hemorrhagic volumes were
      assessed by MRI and neurological evaluation was performed by the string test and
      automated gait analysis. RESULTS: Our in vitro observations showed that memantine
      was able to prevent the proneurotoxic effects of rtPA in cultured cortical
      neurons. Although memantine did not alter the fibrinolytic activity of rtPA, our
      in vivo observations revealed that it blunted the noxious effects of delayed
      thrombolysis on lesion volumes and neurological deficits after ischemic stroke.
      In addition, memantine rescued rtPA-induced decrease in survival rate after
      intracerebral hemorrhage. CONCLUSIONS: Memantine could be used as an adjunct
      therapy to improve the safety of thrombolysis.

PMID- 22879099
TI  - Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study.
AB  - BACKGROUND AND PURPOSE: Aging and vascular risk factors contribute to arterial
      stiffening. Increased arterial stiffness exposes the small vessels in the brain
      to abnormal flow pulsations and, as such, may contribute to the pathogenesis of
      cerebral small vessel disease. In a population-based study, we investigated the
      association between arterial stiffness, as measured by aortic pulse wave velocity
      (aPWV), and small vessel disease. METHODS: Overall, 1460 participants (mean age,
      58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV
      by measuring time differences and distances between pulse waves in the carotid
      and femoral arteries. Using automated MRI analysis, we obtained white matter
      lesion volumes. Infarcts and microbleeds were rated visually. We used linear and
      logistic regression models to associate aPWV with small vessel disease, adjusting
      for age, sex, mean arterial pressure, and heart rate and additionally for
      cardiovascular risk factors. Subsequently, we explored associations in strata of
      hypertension. RESULTS: In the study group, higher aPWV was associated with larger
      white matter lesion volume (difference in volume per SD increase in aPWV 0.07;
      95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with
      uncontrolled hypertension, higher aPWV was significantly associated with larger
      white matter lesion volume (difference in volume per SD increase in aPWV 0.09;
      95% CI, 0.00-0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16
      3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98
      2.70). No such associations were present in persons with controlled hypertension
      or without hypertension. CONCLUSIONS: In our study, increased arterial stiffness
      is associated with a larger volume of white matter lesions.

PMID- 22879100
TI  - Cerebrovascular disease and mechanisms of cognitive impairment: evidence from
      clinicopathological studies in humans.

PMID- 22879101
TI  - Aneurysms increase the risk of rebleeding after stereotactic radiosurgery for
      hemorrhagic arteriovenous malformations.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to define the risk of
      rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous
      malformations with or without associated intracranial aneurysms. METHODS: Between
      1987 and 2006, we performed Gamma Knife SRS on 996 patients with brain
      arteriovenous malformations; 407 patients had sustained an arteriovenous
      malformation hemorrhage. Sixty-four patients (16%) underwent prior embolization
      and 84 (21%) underwent prior surgical resection. The median target volume was 2.3
      mL (range, 0.1-20.7 mL). The median margin dose was 20 Gy (range, 13.5-27 Gy).
      RESULTS: The overall rate of total obliteration defined by angiography or MRI was
      56%, 77%, 80%, and 82% at 3, 4, 5, and 10 years, respectively. Before
      obliteration, 33 patients (8%) sustained an additional hemorrhage after SRS. The
      overall annual hemorrhage rate until obliteration after SRS was 1.3%. The
      presence of a patent aneurysm was significantly associated with an increased
      rehemorrhage risk after SRS (annual hemorrhage rate, 6.4%) compared with patients
      with a clipped or embolized aneurysm (annual hemorrhage rate, 0.8%; P=0.033).
      CONCLUSIONS: When an aneurysm is identified in patients with arteriovenous
      malformations selected for SRS, additional endovascular or surgical strategies
      should be considered to reduce the risk of bleeding during the latency interval.

PMID- 22879102
TI  - [Not Available].

PMID- 22879103
TI  - [Not Available].

PMID- 22879104
TI  - [Not Available].

PMID- 22879105
TI  - [Not Available].

PMID- 22879106
TI  - The inheritance of halothane susceptibility in pigs.

PMID- 22879107
TI  - How to be a self-fertile hermaphrodite.

PMID- 22879108
TI  - Selection on selected records.

PMID- 22879109
TI  - [Not Available].

PMID- 22879110
TI  - [Not Available].

PMID- 22879111
TI  - [Not Available].

PMID- 22879112
TI  - Clinical manifestations, serology and epidemiology of Guillain-Barre syndrome.

PMID- 22879113
TI  - Overwork, stroke, and karoshi-death from overwork.
AB  - Karoshi, death from over-work, is usually the extreme result of acute
      cardiovascular events including stroke. Among 203 karoshi cases received worker
      compensation in Japan, sixty percent died of stroke. Karoshi is a term for social
      medicine originated form Japan. Literature reviews on karoshi found that long
      overtime at work, on duty in holidays, attending a new job with no family members
      around, and working at night shift are risk factors. Work stress increases
      secretion of catecholamines (epinephrine and norepinephrine) and cortisol which
      is associated with progression of atherosclerosis and increased risk of
      cardiovascular diseases and stroke. To avoid long working hours, stress
      management and treatment of hypertension, diabetes, and hyperlipidemia are key
      issues in preventing karoshi caused by stroke.

PMID- 22879114
TI  - Seasonal variation of Guillain-Barre syndrome admission in a large tertiary
      referral center in southern Iran: a 10 year analysis.
AB  - INTRODUCTION: Guillain-Barre syndrome (GBS) is an acute, acquired, monophasic
      peripheral neuropathy which has become the most common cause of acute flaccid
      paralysis. This is an epidemiological report on the seasonal and monthly
      distribution of GBS and certain patient characteristics in Shiraz, Iran. METHODS:
      We extracted data from Namazi hospital records retrospectively in a 10 year
      period (January 2000 to December 2009), the largest tertiary referral center in
      the south of Iran. In order to compare the frequency of GBS in different months
      and seasons we used the Chi Square test. In a separate analysis a comparison was
      made between two subsets of patients regarding sex, duration of admission, month
      and season of admission. RESULTS: From 389 cases of GBS, 232 (59.6%) were male
      and 157 (40.4%) were female. There was seasonal (P=0.004) and monthly (P=0.046)
      variation. Spring and winter had the most amount of patients, with admissions
      from the month of February through June inclusive accounting for 50% of all
      cases. CONCLUSION: Our study shows that there is significant monthly and seasonal
      variation in the admission rate of patients with GBS in Shiraz.

PMID- 22879115
TI  - Montreal cognitive assessment in assessing clinical severity and white matter
      hyperintensity in Alzheimer's disease with normal control comparison.
AB  - PURPOSE: Use Taiwanese version of the Montreal Cognitive Assessment (MoCA) in
      evaluating patients in different stages of Alzheimer's disease (AD) and correlate
      with white matter change. METHODS: Ninety-seven normal controls (NC), 52 very
      mild AD (clinical dementia rating [CDR] = 0.5), 48 mild AD (CDR = 1) and 38
      moderate AD (CDR = 2) patients were enrolled for the MoCA, Mini- Mental State
      Examination (MMSE) and the Cognitive Assessment Screening Instrument (CASI).
      White matter hyperintensities (WMHs) on brain MRI were visually rated and
      classified as deep or periventricular WMHs. RESULTS: In NC group, education (beta
      = 0.326) but not age (beta = -0.183, p = 0.069), was significantly related to
      MoCA score. However, while we added two points to the AD patients with less than
      6 years education, the effects of education disappeared as compared with those of
      7 years of education. For all educational levels, the cutoff value of MoCA for
      very-mild AD was 22/23 (sensitivity = 82.7%, specificity = 87.6%). No significant
      differences were found in the areas under the curves that differentiated NC from
      the patients with AD for MoCA and MMSE (differences = 0.008, p = 0.490), or for
      MoCA and CASI (differences = 0.023, p = 0.082). Total WMHs, frontal deep and
      periventricular WMHs were inversely correlated with the attention and delayed
      recall subdomain. CONCLUSION: The MoCA is a good clinical tool for screening very
      mild stage AD if the educational effects are carefully considered. The
      correlation between the executive subdomains with the frontal WMHs also makes it
      a useful tool for detecting subtle WMHs.

PMID- 22879116
TI  - Metronidazole-induced Encephalopathy: Case Report and Review Literature.
AB  - PURPOSE: Neurotoxicities resulting from various medications are under diagnosed;
      Metronidazole-induced encephalopathy is one of them. Here we present two patients
      with a history of metronidazole use and discuss neuroimaging findings. CASE
      REPORT: We report two patients suffering from acute neurological symptoms
      associated with metronidazole use. A 70-year-old female who received a cumulative
      dose of 41.25g of metronidazole within one month, developed seizure. Brain
      magnetic resonance imaging (MRI) showed T2 hyperintensity over bilateral dentate
      nuclei and dorsal midbrain. A 56-year-old female suffering from acute onset of
      central vertigo with metronidazole use, took a total dose of 24g. The brain MRI
      showed T2 hyperintensity over dorsal midbrain and dorsal medulla, which
      disappeared in the following neuroimaging 50 days later. Metronidazole-induced
      encephalopathy (MIE) was suspected in both patients. CONCLUSION: Metronidazole
      induced encephalopathy is an uncommon but potentially reversible disease in
      patients with acute neurological deficits from the use of metronidazole.
      Nonalcoholic Wernicke's encephalopathy may share a similar metabolic pathway with
      MIE, resulting in difficulties in diagnosis.

PMID- 22879117
TI  - Post-infectious opsoclonus and reversible magnetic resonance imaging changes: a
      case report and review of the literatures.
AB  - PURPOSE: Opsoclonus is a rare neurological disorder in adult. The etiology of
      opsoclonus includes parainfectious, paraneoplastic, toxic, and metabolic
      disorders. We reported an old female with post-infectious opsoclonus who had a
      benign clinical course and reversible brain MRI lesions, and its review of the
      literature. CASE REPORT: A 67-year-old woman presented with opsoclonus and
      truncal ataxia for two weeks. The magnetic resonance imaging (MRI) showed the
      hyperintensity lesions in bilateral medial thalamus, hypothalamus, and tegmentum
      of pons on Fluid-attenuated inversion recovery (FLAIR) imaging. Investigations of
      neoplasm and autoimmune disorders showed negative findings. Clinical symptoms
      subsided in two-week duration and MRI abnormalities also disappeared one month
      later. CONCLUSION: A benign clinical course and reversible MRI lesions could be
      found in the patients with postinfectious opsoclonus such as our case. However,
      detailed investigations and long-term follow-up are needed to exclude
      paraneoplastic or other systemic and immunological disorders.

PMID- 22879118
TI  - Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient
      with Parkinson's disease after deep brain stimulation.
AB  - PURPOSE: To illustrate the beneficial effect of zolpidem on the neuropsychiatric
      and motor symptoms in a patient with Parkinson disease (PD) after bilateral
      subthalamic nucleus deep brain stimulation. CASE REPORT: The 61-year-old
      housewife was diagnosed to have PD for 12 years with initial presentation of
      clumsiness and rest tremor of right limbs. She was referred to our hospital in
      March 2009 due to shortening of drug beneficial period since 3 years ago and on
      phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June,
      2009. Fluctuating spells of mental confusion were developed on the next day after
      surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2
      volts, 60 MUs, 130 Hz on bilateral STN 32 days after DBS. The incoherent
      behaviors and motor fluctuation remained to occur. The beneficial effect of
      zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in
      early July 2009. She could chat normally with her caregiver and walk with
      assistance after taking zolpidem. The beneficial period may last for 2 hours.
      Zolpidem was then given in dosage of 10 mg three times per day. The
      neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during
      zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during
      'off' and 'on' zolpidem conditions. The results revealed that the metabolism was
      decreased in the right frontal, parietal cortex and caudate nucleus during
      zolpidem 'off'. These cool spots can be partially restored by zolpidem.
      CONCLUSION: Zolpidem ameliorated the neuropsychiatric and parkinsonian motor
      symptom in the PD patient. Since GABAA benzodiazepine receptors are widely
      distributed throughout the central nervous system, zolpidem probably acts via
      modulating structures lying within the cortico-subcortical loop or by direct
      effect on these cortical regions.

PMID- 22879119
TI  - Adult Klebsiella pneumoniae meningitis in Taiwan: an overview.
AB  - Klebsiella (K.) pneumoniae infections, including adult bacterial meningitis
      (ABM), are a distinct syndrome in Taiwan, which may consist of diabetes mellitus
      and multiple septic metastatic lesions such as liver abscess, endophthalmitis,
      and focal suppuration of other internal organs. In this review article, the
      authors will discuss the protean clinical manifestations and the complexity of
      the clinical course of this specific central nervous system infectious disease in
      Taiwan. The clinical and laboratory data of 49 K. pneumoniae ABM cases diagnosed
      at Chang Gung Memorial Hospital-Kaohsiung, collected over a period of 11 years
      (2000-2010), were included for analysis. This review may help clinical
      physicians, especially first-line, primary- care physicians, to have a better
      understanding of this critical CNS infection.

PMID- 22879120
TI  - Artery of Percheron infarction.
AB  - Artery of Percheron (AOP) is small perforating arteries supplying paramedian
      thalamus and mid-brain. The incidence of infarction is rare. We presented a 62
      year-old man found conscious drowsy for 4 days. MRI revealed bilateral thalamic
      and midbrain infarction due to AOP occlusion.

PMID- 22879121
TI  - [Not Available].

PMID- 22879123
TI  - Sire evaluation for ordered categorical data with a threshold model.

PMID- 22879122
TI  - Genetic properties of North African Drosophila melanogaster and comparison with
      European and Afrotropical populations.

PMID- 22879124
TI  - [Not Available].

PMID- 22879125
TI  - [Not Available].

PMID- 22879126
TI  - [Not Available].

PMID- 22879127
TI  - Association of egg traits and feathering mutants in domestic fowl.

PMID- 22879129
TI  - [Not Available].

PMID- 22879128
TI  - [Not Available].

PMID- 22879130
TI  - [Not Available].

PMID- 22879131
TI  - Interspecific competition between Drosophila melanogaster and Drosophila
      simulans: temperature effect on competitive ability and fitness components.

PMID- 22879132
TI  - [Not Available].

PMID- 22879133
TI  - Best linear unbiased prediction when error vector is correlated with other random
      vectors in the model.

PMID- 22879134
TI  - Prediction of genetic merit from data on binary and quantitative variates with an
      application to calving difficulty, birth weight and pelvic opening.

PMID- 22879135
TI  - On the estimation of genetic parameters via variance components.

PMID- 22879136
TI  - Mating frequency in male chickens: crosses among selected and unselected lines.

PMID- 22879137
TI  - The prevalence of heterozygotes for alpha-mannosidosis in populations of Angus,
      Galloway and Murray Grey cattle in New South Wales.

PMID- 22879138
TI  - C-band variants of telocentric chromosomes in swine: evidence and inheritance
      studies.

PMID- 22879139
TI  - [Not Available].

PMID- 22879141
TI  - An attempt to modify allelic frequencies at the Adh locus of a Drosophila
      melanogaster population in a tropical environment.

PMID- 22879140
TI  - [Not Available].

PMID- 22879142
TI  - Bidirectional selection for olfactory response to acetaldehyde and ethanol in
      Drosophila melanogaster.

PMID- 22879143
TI  - Production of viable hybrids in salmonids by triploidization.

PMID- 22879144
TI  - Growth curves of highly inbred lines of fowl and their F(1 )hybrids.

PMID- 22879145
TI  - [Not Available].

PMID- 22879146
TI  - Allozyme variation in natural populations of Lymantria dispar (Lepidoptera).

PMID- 22879147
TI  - The geographical distribution of P-M hybrid dysgenesis in Drosophila
      melanogaster.

PMID- 22879148
TI  - [Not Available].

PMID- 22879149
TI  - Population crash, population flush and genetic variability in cage populations of
      Drosophila melanogaster.

PMID- 22879150
TI  - [Not Available].

PMID- 22879151
TI  - Differences in adaptive abilities of three breeds of Chinese pigs. Behavioural
      and neuroendocrine studies.

PMID- 22879153
TI  - The effect on egg laying of crosses made in Tribolium castaneum between lines
      selected for high and low responsiveness to conditioned medium.

PMID- 22879152
TI  - Single and two-stage selection on different indices in open nucleus breeding
      systems.

PMID- 22879154
TI  - [Not Available].

PMID- 22879155
TI  - Two abnormal chromosomes found in one cell line of a mosaic cow with low
      fertility.

PMID- 22879156
TI  - Genetic differentiation between natural populations of Drosophila subobscura in
      the Western Mediterranean Area with respect to chromosomal variation.

PMID- 22879157
TI  - [Not Available].

PMID- 22879158
TI  - The use of prior information in the estimation of heritability by parent
      offspring regression.

PMID- 22879159
TI  - [Not Available].

PMID- 22879160
TI  - [Not Available].

PMID- 22879162
TI  - [Not Available].

PMID- 22879161
TI  - [Not Available].

PMID- 22879163
TI  - [Not Available].

PMID- 22879164
TI  - Detailed description of RBA-banded chromosomes of river buffalo (Bubalus bubalis
      L.).

PMID- 22879165
TI  - [Not Available].

PMID- 22879167
TI  - Estimation of genetic merit from bivariate " all or none " responses.

PMID- 22879166
TI  - Variation in organophosphate resistance and esterase activity in Culex
      quinquefasciatus Say from California.

PMID- 22879168
TI  - [Not Available].

PMID- 22879169
TI  - [Not Available].

PMID- 22879170
TI  - [Not Available].

PMID- 22879171
TI  - [Not Available].

PMID- 22879172
TI  - [Not Available].

PMID- 22879173
TI  - Escherichia coli K88 adhesion: A comparison of Chinese and Large White piglets.

PMID- 22879174
TI  - [Not Available].

PMID- 22879175
TI  - Linkage in cattle between the major histocompatibility complex (BoLA) and the M
      blood group system.

PMID- 22879176
TI  - [Not Available].

PMID- 22879177
TI  - Conditional probabilities of identity of genes at a locus linked to a marker.

PMID- 22879179
TI  - [Not Available].

PMID- 22879178
TI  - [Not Available].

PMID- 22879180
TI  - [Not Available].

PMID- 22879181
TI  - [Not Available].

PMID- 22879182
TI  - [Not Available].

PMID- 22879184
TI  - Effects of winter on genetic structure of a natural population of Drosophila
      melanogaster.

PMID- 22879183
TI  - [Not Available].

PMID- 22879185
TI  - Population genetics of the metabolically related Adh, Gpdh and Tpi polymorphisms
      in Drosophila melanogaster : II. Temporal and Spatial Variation in an Orchard
      Population.

PMID- 22879186
TI  - Allozyme frequency changes in two inverse sequences of environments in Drosophila
      melanogaster.

PMID- 22879187
TI  - [Not Available].

PMID- 22879188
TI  - Evolutionary relationships in the Sativa group of Oryza based on isozyme data.

PMID- 22879189
TI  - Linear versus nonlinear methods of sire evaluation for categorical traits: a
      simulation study.

PMID- 22879191
TI  - Genetic parameters of French beef breeds used in crossbreeding for young bull
      production. I. - Live performance.

PMID- 22879190
TI  - [Not Available].

PMID- 22879192
TI  - Maternal age, development time, position effect variegation in Drosophila
      melanogaster.

PMID- 22879193
TI  - Chromosome abnormalities in embryos from lines of Japanese quail divergently
      selected for body weight.

PMID- 22879194
TI  - Nonhistone chromosomal protein patterns in leucocytes of inbred chicken and their
      crosses.

PMID- 22879195
TI  - Allozyme variation in fourteen natural populations of Drosophila melanogaster
      collected from different regions of France.

PMID- 22879196
TI  - Thoracic trident pigmentation in Drosophila melanogaster: Differentiation of
      geographical populations.

PMID- 22879197
TI  - Population genetics of French brown trout (Salmo trutta L): large geographical
      differentiation of wild populations and high similarity of domesticated stocks.

PMID- 22879198
TI  - Genetic variation of flesh colour in canthaxanthin fed rainbow trout.

PMID- 22879199
TI  - Selection for large and small litter size of the first three litters in mice.

PMID- 22879200
TI  - Genetic parameters of french beef breeds used in crossbreeding for young bull
      production. II. - Slaughter performance.

PMID- 22879201
TI  - Electrophoretic serum protein fractions in dwarf and normal layer hens and their
      correlations with productive traits.

PMID- 22879202
TI  - Global gene expression analysis in cord blood reveals gender-specific differences
      in response to carcinogenic exposure in utero.
AB  - BACKGROUND: It has been suggested that fetal carcinogenic exposure might lead to
      predisposition to develop cancer during childhood or in later life possibly
      through modulation of the fetal transcriptome. Because gender effects in the
      incidence of childhood cancers have been described, we hypothesized differences
      at the transcriptomic level in cord blood between male and female newborns as a
      consequence of fetal carcinogenic exposure. The objective was to investigate
      whether transcriptomic responses to dietary genotoxic and nongenotoxic
      carcinogens show gender-specific mechanisms-of-action relevant for chemical
      carcinogenesis. METHODS: Global gene expression was applied in umbilical cord
      blood samples, the CALUX-assay was used for measuring dioxin(-like), androgen(
      like), and estrogen(-like) internal exposure, and acrylamide-hemoglobin adduct
      levels were determined by mass spectrometry adduct-FIRE-procedure(TM). To link
      gene expression to an established phenotypic biomarker of cancer risk,
      micronuclei frequencies were investigated. RESULTS: While exposure levels did not
      differ between sexes at birth, important gender-specific differences were
      observed in gene expressions associated with these exposures linked with cell
      cycle, the immune system and more general cellular processes such as
      posttranslation. Moreover, oppositely correlating leukemia/lymphoma genes between
      male and female newborns were identified in relation to the different biomarkers
      of exposure that might be relevant to male-specific predisposition to develop
      these cancers in childhood. CONCLUSIONS/IMPACT: This study reveals different
      transcriptomic responses to environmental carcinogens between the sexes. In
      particular, male-specific TNF-alpha-NF-kB signaling upon dioxin exposure and
      activation of the Wnt-pathway in boys upon acrylamide exposure might represent
      possible mechanistic explanations for gender specificity in the incidence of
      childhood leukemia.

PMID- 22879203
TI  - Associations of serum sex steroid hormone and 5alpha-androstane-3alpha,17beta
      diol glucuronide concentrations with prostate cancer risk among men treated with
      finasteride.
AB  - BACKGROUND: Finasteride, an inhibitor of 5alpha-reductase (type II), lowers
      intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced
      5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-dG). It also modestly
      increases serum testosterone (T), estrone (E(1)), and estradiol (E(2)). In this
      altered hormonal milieu, it is unknown whether serum concentrations of these
      hormones are associated with prostate cancer risk. METHODS: In this nested case
      control study of men in the finasteride arm of the Prostate Cancer Prevention
      Trial, sex steroid hormones and sex hormone binding globulin were measured at
      baseline and approximately 3-year posttreatment in 553 prostate cancer cases and
      694 controls. RESULTS: Median posttreatment changes in concentrations of 3alpha
      dG, T, E(1), and E(2) were -73.8%, +10.1%, +11.2%, and +7.5% (all P < 0.001),
      respectively. Neither the pre- nor posttreatment concentrations of 3alpha-dG, nor
      its change, were associated with risk. Pretreatment, high concentrations of E(1)
      and low concentrations of T were associated with increased cancer risk [OR; 95%
      confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) P(trend) = 0.03; 0.64
      (0.43-0.93) P(trend) = 0.07, respectively]. Posttreatment, high concentrations of
      both E(1) and E(2) were associated with increased cancer risk [OR; 95% CI
      quartile 4 vs. 1: 1.54 (1.09-2.17) P(trend) = 0.03; 1.49 (1.07-2.07) P(trend) =
      0.02, respectively]. CONCLUSIONS: Among finasteride-treated men, concentrations
      of 3alpha-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or
      8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic
      DHT is pharmacologically lowered. IMPACT: Low posttreatment serum estrogens may
      identify men more likely to benefit from use of finasteride to prevent prostate
      cancer.

PMID- 22879204
TI  - Prediagnostic plasma pyridoxal 5'-phosphate (vitamin b6) levels and invasive
      breast carcinoma risk: the multiethnic cohort.
AB  - BACKGROUND: Evidence from experimental and epidemiologic studies suggests that
      vitamin B6 may reduce the risk of breast cancer. METHODS: We examined the
      association of prediagnostic plasma concentrations of pyridoxal-5'-phosphate
      (PLP), an active form of vitamin B6, with postmenopausal breast cancer risk in a
      case-control study nested in the multiethnic cohort in Hawaii and Southern
      California, including 706 cases and 706 controls matched on date of birth,
      ethnicity, study site, date of blood draw, time of blood draw, hours of fasting
      before blood draw, and use of menopausal hormones. OR and 95% confidence
      intervals (CI) were calculated using conditional logistic regression models.
      RESULTS: Women with plasma PLP concentrations in the highest quartile had a 30%
      reduced risk of invasive breast cancer (CI: 0.50-0.98) as compared with the women
      in the lowest PLP quartile (P for trend = 0.02). The association seemed to be
      limited in cases with hormone receptor-positive tumors (P for heterogeneity =
      0.04); and remained unchanged in the analysis restricted to women with blood
      samples collected more than one year before cancer diagnosis (OR = 0.69; CI: 0.48
      0.99; P for trend = 0.03). CONCLUSIONS: These data suggest that higher
      circulating levels of vitamin B6 are associated with a reduced risk of invasive
      postmenopausal breast cancer. IMPACT: These results, in combination with
      information from two other prospective studies, suggest a role for vitamin B6 in
      the prevention of postmenopausal breast cancer. Additional studies are needed to
      further investigate potential heterogeneity of the vitamin B6 association with
      breast cancer risk by tumor hormone receptor status.

PMID- 22879205
TI  - Statin use and risk of prostate cancer in the prospective Osteoporotic Fractures
      in Men (MrOS) Study.
AB  - BACKGROUND: Statins are a common medication for cholesterol control that may also
      have effects on cancer-related pathways. The evidence of an association between
      statins and prostate cancer risk remains ambiguous. METHODS: We examined statin
      use in a prospective cohort of 5,069 elderly U.S. men and the risk of incident
      total, low/high stage, and low/high grade prostate cancer diagnosed between 2000
      and 2008. We used multivariate logistic regression models to estimate relative
      risks and 95% confidence intervals, adjusting for demographic and lifestyle
      characteristics. RESULTS: There was no evidence of an association between statin
      use and any of the prostate cancer endpoints (total, low/high stage, low/high
      grade prostate cancer), adjusting for age, study site, race, body mass index,
      marital status, family history of prostate cancer, number of comorbidities,
      physical activity, and smoking history. CONCLUSIONS AND IMPACT: In this study of
      elderly U.S. men, we observed a null association between statin use and risk of
      prostate cancer.

PMID- 22879207
TI  - A 1/29 chromosome translocation in Southern African Nguni cattle. The
      identification, occurrence and origin of the translocation.

PMID- 22879206
TI  - Insulin therapy and colorectal adenomas in patients with diabetes mellitus.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (DM) are at increased risk for
      colorectal adenomas and cancer because of endogenous hyperinsulinemia. Exogenous
      insulin therapy has been associated with higher colorectal cancer incidence. The
      aim of this study was to evaluate the association between exogenous insulin
      therapy and adenoma formation, accounting for duration of therapy and location
      and stage of the adenoma. METHODS: We conducted a cross-sectional study of
      patients with type 2 diabetes between the ages of 50 and 80 years who completed
      full colonoscopies. Cases were patients with any adenoma on index colonoscopy.
      Patients without any adenoma composed the control group. Multivariable logistic
      regression was used to calculate odds ratios (OR) and associated confidence
      intervals (CI). RESULTS: Compared with the controls, case patients (n = 196) did
      not have a significantly increased odds of insulin exposure, when exposure was
      defined as 12 months or more of insulin use compared with no insulin. However,
      the odds of insulin exposure among the cases was significantly increased when
      exposure was defined as 18 months or more (OR 1.6, 95% CI 1.1-2.5), 24 months or
      more (OR 1.7, CI 1.1-2.6), and 36 months or more (OR 2.0, 95% CI 1.2-3.4) of
      insulin use (test for trend P = 0.05). A similar trend in insulin exposure was
      seen among type 2 diabetics with advanced adenomas. Adenoma location was not
      significantly affected by insulin therapy. CONCLUSIONS: Chronic insulin therapy
      is associated with increased risk of colorectal adenomas in patients with type 2
      diabetes. IMPACT: Diabetes patients receiving insulin may need more stringent
      colon cancer screening.

PMID- 22879208
TI  - [Not Available].

PMID- 22879209
TI  - [Not Available].

PMID- 22879210
TI  - Effect of alcohol and competition levels on viability of eye colour mutants of
      Drosophila melanogaster.

PMID- 22879211
TI  - [Not Available].

PMID- 22879212
TI  - Fixation probabilities of mutant genes with artificial selection.

PMID- 22879213
TI  - On the genetic determinism of muscular hypertrophy in the Belgian White and Blue
      cattle breed. I. Experimental data.

PMID- 22879214
TI  - On the genetic determinism of muscular hypertrophy in the Belgian White and Blue
      cattle breed. II. Population data.

PMID- 22879215
TI  - Efficient selection rules to increase non-linear merit: application in mate
      selection.

PMID- 22879216
TI  - [Not Available].

PMID- 22879217
TI  - [Not Available].

PMID- 22879218
TI  - Variation of allozyme frequencies in Spanish field and cellar populations of D.
      melanogaster.

PMID- 22879219
TI  - Coat colour inheritance in the Belgian White and Blue cattle breed.

PMID- 22879220
TI  - [Not Available].

PMID- 22879222
TI  - [Not Available].

PMID- 22879221
TI  - [Not Available].

PMID- 22879223
TI  - [Not Available].

PMID- 22879224
TI  - [Not Available].

PMID- 22879225
TI  - [Not Available].

PMID- 22879227
TI  - Genetic disequilibria between the alpha(S1)-, beta-, kappa-casein and the beta
      lactoglobulin loci of the Bavarian Brown and Bavarian Simmental cattle.

PMID- 22879226
TI  - [Not Available].

PMID- 22879228
TI  - Variable outcome in competition experiments between Drosophila melanogaster and
      Drosophila simulans.

PMID- 22879229
TI  - Constructing categories for polychotomous variates.

PMID- 22879230
TI  - Computing genetic evaluations through application of generalized least squares to
      an animal model.

PMID- 22879231
TI  - Computing algorithm for dairy sire evaluation on several lactations considered as
      the same trait.

PMID- 22879232
TI  - [Not Available].

PMID- 22879233
TI  - [Not Available].

PMID- 22879234
TI  - [Not Available].

PMID- 22879235
TI  - The gene map of the rabbit. III. alpha and beta casein gene synteny.

PMID- 22879236
TI  - [Not Available].

PMID- 22879237
TI  - A new reciprocal translocation in a hypoprolific boar.

PMID- 22879238
TI  - Endemic microorganisms of a Drosophila simulans strain and their relationships
      with the non-mendelian transmission of a character.

PMID- 22879239
TI  - Prenatal and postnatal correlated responses in maternal traits of mice assessed
      by crossfostering.

PMID- 22879240
TI  - [Not Available].

PMID- 22879241
TI  - Heritability of a canalized trait: teat number in Iberian pigs.

PMID- 22879242
TI  - Estimated genetic trends for growth and carcass traits in two French pig breeds.

PMID- 22879244
TI  - [Not Available].

PMID- 22879243
TI  - [Not Available].

PMID- 22879245
TI  - [Not Available].

PMID- 22879246
TI  - [Not Available].

PMID- 22879247
TI  - [Not Available].

PMID- 22879248
TI  - Numerical techniques for the analysis of polygenes sampled from natural
      populations.

PMID- 22879249
TI  - Genetic evaluation for multiple binary responses.

PMID- 22879250
TI  - [Not Available].

PMID- 22879251
TI  - Components of prolificacy in hyperprolific Large White sows compared with the
      Meishan and Large White breeds.

PMID- 22879252
TI  - [Not Available].

PMID- 22879253
TI  - Speciation burst hypothesis: an explanation for the variation in rates of
      phenotypic evolution.

PMID- 22879254
TI  - A Robertsonian translocation in swine.

PMID- 22879256
TI  - Gene segregation in gynogenetic brown trout (Salmo trutta L.): systematically
      high frequencies of post-reduction.

PMID- 22879255
TI  - Pig gene mapping: assignment of the genes for mannosephosphate isomerase (MPI)
      and nucleoside phosphorylase (NP) to chromosome no. 7.

PMID- 22879257
TI  - [Not Available].

PMID- 22879258
TI  - Alcohol tolerance and Adh gene frequencies in European and African populations of
      Drosophila melanogaster.

PMID- 22879259
TI  - Enzymatic heterozygosity and morphological variance in synthetic populations of
      Drosophila melanogaster.

PMID- 22879260
TI  - Selection for abdominal bristle number in Drosophila subobscura, a highly
      polymorphic species for gene arrangements.

PMID- 22879261
TI  - Experimental comparison of methods for simultaneous selection of two correlated
      traits in Tribolium. 2. Index selection and independent culling levels: a
      replicated single generation test.

PMID- 22879262
TI  - Interest in quantitative genetics of Dutt's and Deak's methods for numerical
      computation of multivariate normal probability integrals.

PMID- 22879263
TI  - Estimation of realized heritability in a selected population using mixed model
      methods.

PMID- 22879264
TI  - Prediction of breeding values when variances are not known.

PMID- 22879265
TI  - Re-examination of selection index for desired gains.

PMID- 22879266
TI  - [Not Available].

PMID- 22879267
TI  - A cytogenetic investigation on peripheral blood lymphocytes of cattle affected by
      enzootic bovine leukemia.

PMID- 22879268
TI  - Segregation of blood group factors in horses with special reference to maternal
      fetal incompatibility.

PMID- 22879269
TI  - Sexual isolation between Drosophila melanogaster females and Drosophila simulans
      males. I - Relation between homospecific and heterospecific mating success.

PMID- 22879270
TI  - Environment-dependent heterosis in Drosophila melanogaster.

PMID- 22879271
TI  - Restricted Maximum Likelihood to estimate variance components for mixed models
      with two random factors.

PMID- 22879272
TI  - Comparisons of selection indices achieving predetermined proportional gains.

PMID- 22879273
TI  - Sire evaluation with uncertain paternity.

PMID- 22879274
TI  - [Not Available].

PMID- 22879275
TI  - [Not Available].

PMID- 22879276
TI  - Segregational patterns of a chromosome insertion in the progeny of twin chimeric
      bulls.

PMID- 22879278
TI  - Phenotypic and genotypic differentiation in cage populations of Drosophila
      melanogaster. I. Duration of development, thorax size and weight.

PMID- 22879277
TI  - [Not Available].

PMID- 22879279
TI  - Expectation of variance due to mitochondrial genes from several mating designs.

PMID- 22879280
TI  - Assortative mating and artificial selection: a second appraisal.

PMID- 22879282
TI  - Relationships between growth rate, carcass composition, feed intake, feed
      conversion ratio and income in four biological types of cattle.

PMID- 22879281
TI  - Empirical Bayes estimation of parameters for n polygenic binary traits.

PMID- 22879283
TI  - [Not Available].

PMID- 22879284
TI  - Genotype diet interaction in Fayoumi and Rhode Island Red layers and their
      crosses.

PMID- 22879285
TI  - Rabbit mitochondrial DNA: preliminary comparison between some domestic and wild
      animals.

PMID- 22879286
TI  - Polymorphisms of inversions and Adh alleles in eye colour mutant experimental
      populations of Drosophila melanogaster.

PMID- 22879287
TI  - Low frequency of inversion-carrying chromosomes in a population of Drosophila
      melanogaster from a cellar habitat.

PMID- 22879288
TI  - [Not Available].

PMID- 22879289
TI  - Portfolio theory, utility theory and mate selection.

PMID- 22879290
TI  - Genetic parameters for first lactation dairy traits in Friesian, Montbeliarde and
      Normande breeds.

PMID- 22879291
TI  - [Not Available].

PMID- 22879292
TI  - [Not Available].

PMID- 22879293
TI  - A new reciprocal translocation involving chromosomes 1/14 in a boar.

PMID- 22879294
TI  - Cytogenetic observations on a Robertsonian translocation in Saanen goats.

PMID- 22879295
TI  - A Mendelian polymorphism underlying quantitative variations of goat alpha(s1)
      casein.

PMID- 22879296
TI  - [Not Available].

PMID- 22879297
TI  - Intra- and intergenotypic larval competition in Drosophila melanogaster : effect
      of larval density and biotic residues.

PMID- 22879298
TI  - Direct and correlated responses to selection for large and small 6-week body
      weight in mice.

PMID- 22879299
TI  - Studies on dairy production of milking ewes. I. - Estimates of genetic parameters
      for total milk composition and yield.

PMID- 22879300
TI  - [Not Available].

PMID- 22879301
TI  - Population genetics and the Cretaceous extinction.

PMID- 22879302
TI  - Linkage disequilibrium between enzymatic loci in natural populations of
      Drosophila simulans.

PMID- 22879303
TI  - Variation at four enzyme loci in natural populations of Drosophila melanogaster :
      factor analyses of genotypic and gametic associations.

PMID- 22879304
TI  - Variability of eye colour mutations in natural populations of Drosophila
      melanogaster.

PMID- 22879305
TI  - [Not Available].

PMID- 22879306
TI  - [Not Available].

PMID- 22879307
TI  - [Not Available].

PMID- 22879308
TI  - Chromosomal analysis of selected lines of Drosophila melanogaster with a new
      level of bristle canalization.

PMID- 22879309
TI  - The analysis of quantitative variation in natural populations with isofemale
      strains.

PMID- 22879310
TI  - Haemoglobin type frequencies in the Assaf (Awassi * East Friesian) dairy sheep 20
      years after its formation.

PMID- 22879312
TI  - [Not Available].

PMID- 22879311
TI  - [Not Available].

PMID- 22879313
TI  - Using temperature of pressure-related intact discolored areas of skin to detect
      deep tissue injury: an observational, retrospective, correlational study.
AB  - Pressure-related intact discolored areas of skin (PRIDAS) are generally described
      as an area of nonblanching erythema (Stage I pressure ulcer) or deep tissue
      injury (DTI), but the validity of these definitions has not been tested.
      Preclinical studies and forensic observations have shown that skin temperature
      may help identify nonviable tissue. To investigate the effect of temperature
      difference between a PRIDAS and its adjacent intact skin and the subsequent
      development of skin necrosis, an observational, retrospective, correlational
      study was conducted. Data from all acute care hospital patients with an observed
      PRIDAS who received a skin integrity consult, including a skin temperature
      measurement of a PRIDAS site, were abstracted to ascertain if PRIDAS temperature
      correlated with the development of skin necrosis after 7 to 14 days and to
      examine the effect of additional patient variables on the progression or
      resolution of a PRIDAS. Skin temperatures were measured using a commercial, hand
      held, infrared thermography camera, and the presence or absence of capillary
      refill was documented. Among the 85 patients studied, the difference between
      PRIDAS temperature and adjacent skin ranged from -3.2  C. to +3.0 C. Of the 55
      PRIDAS with a lower temperature at baseline than adjacent skin ("cool", average 
      1.2  C), 29 progressed to necrosis, compared to one of 30 PRIDAS with a higher
      temperature than adjacent skin ("warm", average + 1.2  C) (P <0.001). After
      adjusting for patient age, skin color, and PRIDAS site, the cool PRIDAS were 31.8
      times more likely to progress to necrosis than the warm PRIDAS. Combining the
      presence/absence of capillary refill and PRIDAS temperature, 0% of 26 patients
      with signs of blanching and a warm PRIDAS versus 65% of 26 patients with a
      nonblanching and cool PRIDAS developed skin necrosis (P <0.001, Fisher exact test
      for the difference between the two combined values). Research examining the
      delayed appearance of DTI and large, multicenter, prospective validation studies
      are warranted. The current National Pressure Ulcer Advisory Panel definition of a
      Stage I pressure ulcer needs to be amended to reflect the strong relationship to
      DTI development.

PMID- 22879314
TI  - Quality of pediatric second-degree burn wound scars following the application of
      basic fibroblast growth factor: results of a randomized, controlled pilot study 
      .
AB  - Pediatric burn wounds present unique challenges. Second-degree burns may
      increase in size and depth, raising concerns about healing and long-term
      scarring. Results of a clinical study in adults with second-degree burn wounds
      suggest that application of basic fibroblast growth factor (bFGF) may reduce time
      to second-intention healing and result in a more cosmetically acceptable scar. To
      evaluate the effect of this treatment on pediatric patients with deep second-
      degree burn wounds, 20 pediatric patients ranging in age from 8 months to 3 years
      (average 1 year, 3 months [+/- 6 months]) with a total of 30 burn wounds from
      various causes were allocated either the growth factor (treatment, n = 15) or an
      impregnated gauze treatment (control, n = 15). Wounds still exudative (not
      healed) after 21 days were covered with a split-thickness skin graft. All wounds
      were clinically assessed until healed and after 1 year. A moisture meter was used
      to assess scars of wounds healing by secondary intention. A color meter was used
      to evaluate grafted wounds. Five wounds in each group required grafting.
      Skin/scar color match was significantly closer to 100% in the treatment than in
      the control group (P <0.01). Wounds not requiring grafting were no longer
      exudative after 13.8 (+/- 2.4) and 17.5 (+/- 3.1) days in the treatment (n = 10)
      and control group (n = 10), respectively (P <0.01). After 1 year, scar
      pigmentation, pliability, height, and vascularity were also significantly
      different (P <0.01) between the groups. Hypertrophic scars developed in 0 of 10
      wounds in the treatment and in three of 10 wounds in the control group, and
      effective contact coefficient, transepidermal water loss, water content, and scar
      thickness were significantly greater in control group (P <0.01). Both the short-
      and long-term results of this treatment in pediatric burn patients are
      encouraging and warrant further research.

PMID- 22879315
TI  - Construction and use of wound care guidelines: an overview.
AB  - Patients should receive care based on the best available scientific knowledge.
      Clinical wound care guidelines have been created using many methodologies, but
      many remain consensus-based. A consensus-based approach is no longer considered
      adequate or appropriate. The best guidelines are developed from a systematic
      examination and appraisal of good evidence from well-conducted trials. The
      development process must be transparent, utilize an accepted evidence rating
      system, be supported by appropriate clinical expertise, and lead to unambiguous
      recommendations. Prospective validation studies are important as part of the
      development process, especially for areas of care with limited literature- based
      evidence. Wound care will become a process of applying the best data available to
      the clinical situation. The ultimate use of guidelines will be the development of
      evidence-based, validated clinical tools that can be integrated with existing
      patient data and available to the wound care professional at the consultation.

PMID- 22879316
TI  - Expression of a quantitative character radius incompletus, temperature effects,
      and localization of a mobile genetic element Dm-412 in Drosophila melanogaster.

PMID- 22879317
TI  - [Not Available].

PMID- 22879318
TI  - Timing and duration of hatching in gynogenetic, triploid, tetraploid, and hybrid
      progenies in rainbow trout.

PMID- 22879319
TI  - A statistical model for genotype determination at a major locus in a progeny test
      design.

PMID- 22879320
TI  - Posterior probability of the sire's genotype at a major locus based on progeny
      test results for discrete characters.

PMID- 22879322
TI  - Identification of the two common alleles of the bovine kappa-casein locus by the
      RFLP technique, using the enzyme Hind III.

PMID- 22879321
TI  - The recent introduction of a 1/29 chromosome translocation in South African
      Brahman cattle.

PMID- 22879323
TI  - Types of red cell potassium in seven Spanish native breeds of cattle.

PMID- 22879324
TI  - Selection for increased and decreased total number of young born in the first
      three parities in mice.

PMID- 22879325
TI  - [Not Available].

PMID- 22879326
TI  - Structural changes of the homologues as a possible cause of abnormal disjunction
      in female mice heterozygous for Robertsonian translocations.

PMID- 22879327
TI  - Microspatial differentiation of Drosophila melanogaster populations in and around
      a wine cellar in southern Spain.

PMID- 22879328
TI  - [Not Available].

PMID- 22879329
TI  - [Not Available].

PMID- 22879330
TI  - [Not Available].

PMID- 22879331
TI  - Reaction to halothane anaesthesia among heterozygotes at the halothane locus in
      British Landrace pigs.

PMID- 22879332
TI  - [Not Available].

PMID- 22879333
TI  - [Not Available].

PMID- 22879334
TI  - [Not Available].

PMID- 22879335
TI  - Search for age-dependent as compared to mutagen-induced mutations on the X
      chromosome affecting viability in Drosophila melanogaster males.

PMID- 22879336
TI  - A test to detect association between autosomal and sex-linked loci in random
      mating populations: an example with Drosophila melanogaster.

PMID- 22879337
TI  - Relationship between density- and frequency-dependent effects in two strains of
      Drosophila melanogaster.

PMID- 22879338
TI  - Electrophoretic detection of interspecific hybrids in Parnassius (Lepidoptera
      Papilionidae).

PMID- 22879339
TI  - [Not Available].

PMID- 22879341
TI  - Environmental and genetic factors affecting udder characters and milk production
      in Chios sheep.

PMID- 22879340
TI  - [Not Available].

PMID- 22879342
TI  - Genetic relationship between prepuberal plasma FSH levels and reproductive
      performance in Lacaune ewe lambs.

PMID- 22879343
TI  - Thyroid hormones and antibody response to sheep erythrocytes of dwarf and normal
      chickens selected for juvenile body weight.

PMID- 22879344
TI  - Threshold models with heterogeneous residual variance due to missing information.

PMID- 22879345
TI  - Point-based manifold harmonics.
AB  - This paper proposes an algorithm to build a set of orthogonal Point-Based
      Manifold Harmonic Bases (PB-MHB) for spectral analysis over point-sampled
      manifold surfaces. To ensure that PB-MHB are orthogonal to each other, it is
      necessary to have symmetrizable discrete Laplace-Beltrami Operator (LBO) over the
      surfaces. Existing converging discrete LBO for point clouds, as proposed by
      Belkin et al., is not guaranteed to be symmetrizable. We build a new point-wisely
      discrete LBO over the point-sampled surface that is guaranteed to be
      symmetrizable, and prove its convergence. By solving the eigen problem related to
      the new operator, we define a set of orthogonal bases over the point cloud.
      Experiments show that the new operator is converging better than other
      symmetrizable discrete Laplacian operators (such as graph Laplacian) defined on
      point-sampled surfaces, and can provide orthogonal bases for further spectral
      geometric analysis and processing tasks.

PMID- 22879346
TI  - Interest driven navigation in visualization.
AB  - This paper describes a new method to explore and discover within a large data
      set. We apply techniques from preference elicitation to automatically identify
      data elements that are of potential interest to the viewer. These "elements of
      interest (EOI)" are bundled into spatially local clusters, and connected together
      to form a graph. The graph is used to build camera paths that allow viewers to
      "tour" areas of interest (AOI) within their data. It is also visualized to
      provide wayfinding cues. Our preference model uses Bayesian classification to tag
      elements in a data set as interesting or not interesting to the viewer. The model
      responds in real time, updating the elements of interest based on a viewer's
      actions. This allows us to track a viewer's interests as they change during
      exploration and analysis. Viewers can also interact directly with interest rules
      the preference model defines. We demonstrate our theoretical results by
      visualizing historical climatology data collected at locations throughout the
      world.

PMID- 22879347
TI  - Why is DNA methylation of Igf2 CpG island shore affected during ageing?

PMID- 22879348
TI  - Space/population and time/age in DNA methylation variability in humans: a study
      on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic
      twins of different age.
AB  - Little is known about the impact of space (geography/ancestry) and time (age of
      the individuals) on DNA methylation variability in humans. We investigated DNA
      methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals
      homogeneous for age and gender (males with restricted age range: 30-50 years)
      belonging to four Italian districts representative of the major genetic clines,
      informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and
      dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for
      the temporal dimension. DNA methylation of the analyzed regions displayed high
      levels of inter-individual variability that could not be ascribed to any
      geographical cline. In MZ twins we identified two IGF2/H19 regions where the
      intra-couple variations significantly increased after the age of 60 years. The
      analysis of twins' individual life histories suggests that the within twin pairs
      difference is likely the result of the aging process itself, as sharing a common
      environment for long periods had no effect on DNA methylation divergence. On the
      whole, the data here reported suggest that: i) aging more than population
      genetics is responsible for the inter-individual variability in DNA methylation
      patterns in humans; ii) DNA methylation variability appears to be highly region
      specific.

PMID- 22879350
TI  - Overnight consolidation aids the transfer of statistical knowledge from the
      medial temporal lobe to the striatum.
AB  - Sleep is important for abstraction of the underlying principles (or gist) which
      bind together conceptually related stimuli, but little is known about the neural
      correlates of this process. Here, we investigate this issue using overnight sleep
      monitoring and functional magnetic resonance imaging (fMRI). Participants were
      exposed to a statistically structured sequence of auditory tones then tested
      immediately for recognition of short sequences which conformed to the learned
      statistical pattern. Subsequently, after consolidation over either 30 min or 24h,
      they performed a delayed test session in which brain activity was monitored with
      fMRI. Behaviorally, there was greater improvement across 24h than across 30 min,
      and this was predicted by the amount of slow wave sleep (SWS) obtained.
      Functionally, we observed weaker parahippocampal responses and stronger striatal
      responses after sleep. Like the behavioral result, these differences in
      functional response were predicted by the amount of SWS obtained. Furthermore,
      connectivity between striatum and parahippocampus was weaker after sleep, whereas
      connectivity between putamen and planum temporale was stronger. Taken together,
      these findings suggest that abstraction is associated with a gradual shift from
      the hippocampal to the striatal memory system and that this may be mediated by
      SWS.

PMID- 22879349
TI  - Neural mechanisms of age-related slowing: the DeltaCBF/DeltaCMRO2 ratio mediates
      age-differences in BOLD signal and human performance.
AB  - The precise mechanisms that give rise to the blood-oxygen-level-dependent (BOLD)
      activation differences that accompany age-related cognitive slowing remain
      fundamentally unknown. We sought to isolate the origin of age-related BOLD
      changes by comparing blood-flow and oxygen-metabolic constituents of the BOLD
      response using dual-echo arterial spin labeling during visual stimulation and CO2
      ingestion. We hypothesized, and our results confirmed, that age-related changes
      in the ratio of fractional cerebral blood flow to fractional cerebral metabolic
      rate of oxygen consumption (DeltaCBF/DeltaCMRO2) lead to the BOLD changes that
      are observed in older adults. DeltaCBF/DeltaCMRO2 was also significantly related
      to performance, suggesting that age-related cognitive slowing results from neural
      cell assemblies that operate less efficiently, requiring greater oxygen
      metabolism that is not matched by blood-flow changes relative to younger adults.
      Age-related changes in DeltaCBF/DeltaCMRO2 are sufficient to explain variations
      in BOLD responding and performance cited throughout the literature, assuming no
      bias based on physiological baseline CMRO2. 

PMID- 22879351
TI  - Impaired processing of 3D motion-defined faces in mild cognitive impairment and
      healthy aging: an fMRI study.
AB  - Mild cognitive impairment (MCI), which shows high risk for conversion to
      Alzheimer's disease (AD), is accompanied by progressive visual deteriorations
      that so far are poorly understood. Here, we compared dorsal and ventral visual
      stream functional magnetic resonance imaging (fMRI) activity among amnestic MCI,
      healthy elderly, and young participants during structure-from-motion (SFM) face
      categorization performance. Task performance varied with stimulus depth and
      duration levels and differences among groups were highly correlated with face
      related fMRI activation patterns. Young participants showed larger activation to
      faces than scrambled faces (face sensitivity) in the right fusiform face area
      (FFA) and right occipital face area (OFA) whereas in elderly, this difference was
      reduced. Surprisingly, in MCI, scrambled faces elicited larger activation in
      right FFA/OFA than faces. The latter observation may be related to the additional
      finding of elevated depth sensitivity in left FFA/OFA of MCI, suggesting that an
      increased representation of low-level stimulus aspects may impair face perception
      in MCI. Discriminant function analysis using face and depth sensitivity indices
      in FFA/OFA classified MCI and healthy elderly with 88.2% accuracy, marking a
      fundamental distinction between groups. Potentially related findings include
      altered activation patterns in dorsal-ventral stream integration regions and
      attention-related networks of MCI patients. Our results highlight aberrant visual
      and additional potentially compensatory processes that identify dispositions of
      (preclinical) AD. 

PMID- 22879352
TI  - Intracranial electroencephalography reveals different temporal profiles for
      dorsal- and ventro-lateral prefrontal cortex in preparing to stop action.
AB  - Preparing to stop an inappropriate action requires keeping in mind the task goal
      and using this to influence the action control system. We tested the hypothesis
      that different subregions of prefrontal cortex show different temporal profiles
      consistent with dissociable contributions to preparing-to-stop, with dorsolateral
      prefrontal cortex (DLPFC) representing the task goal and ventrolateral prefrontal
      cortex (VLPFC) implementing action control. Five human subjects were studied
      using electrocorticography recorded from subdural grids over right lateral
      frontal cortex. On each trial, a task cue instructed the subject whether stopping
      might be needed or not (Maybe Stop [MS] or No Stop [NS]), followed by a go cue,
      and on some MS trials, a subsequent stop signal. We focused on go trials,
      comparing MS with NS. In the DLPFC, most subjects had an increase in high gamma
      activity following the task cue and the go cue. In contrast, in the VLPFC, all
      subjects had activity after the go cue near the time of the motor response on MS
      trials, related to behavioral slowing, and significantly later than the DLPFC
      activity. These different temporal profiles suggest that DLPFC and VLPFC could
      have dissociable roles, with DLPFC representing task goals and VLPFC implementing
      action control. 

PMID- 22879353
TI  - Effects of aging on properties of the local circuit in rat primary somatosensory
      cortex (S1) in vitro.
AB  - During aging receptive field properties degrade, the ability of the circuit to
      process temporal information is impaired and behaviors mediated by the circuit
      can become impaired. These changes are mediated by changes in the properties of
      neural circuits, particularly the balance of excitation and inhibition, the
      intrinsic properties of neurons, and the anatomy of connections in the circuit.
      In this study, properties of thalamorecipient pyramidal neurons in layer 3 were
      examined in the hindpaw region of rat primary somatosensory cortex (S1) in vitro.
      Excitatory and inhibitory postsynaptic currents (IPSCs) resulting from trains of
      electrical stimulation of thalamocortical afferents were recorded. Excitatory
      postsynaptic currents were larger in old S1, but showed no difference in temporal
      dynamics; IPSCs showed significantly less suppression across the train in old S1,
      partly due to a decrease in GABAB signaling. Neurons in old S1 were more likely
      to exhibit burst firing, due to an increase in T-current. Significant differences
      in dendritic morphology were also observed in old S1, accompanied by a decrease
      in dendritic spine density. These data directly demonstrate changes in the
      properties of the thalamorecipient circuit in old S1 and help to explain the
      changes observed in responses during aging. 

PMID- 22879354
TI  - Lateral prefrontal cortex is organized into parallel dorsal and ventral streams
      along the rostro-caudal axis.
AB  - Anatomical connectivity differences between the dorsal and ventral lateral
      prefrontal cortex (PFC) of the non-human primate strongly suggests that these
      regions support different functions. However, after years of study, it remains
      unclear whether these regions are functionally distinct. In contrast, there has
      been a groundswell of recent studies providing evidence for a rostro-caudal
      functional organization, along the lateral as well as dorsomedial frontal cortex.
      Thus, it is not known whether dorsal and ventral regions of lateral PFC form
      distinct functional networks and how to reconcile any dorso-ventral organization
      with the medio-lateral and rostro-caudal axes. Here, we used resting-state
      connectivity data to identify parallel dorsolateral and ventrolateral streams of
      intrinsic connectivity with the dorsomedial frontal cortex. Moreover, we show
      that this connectivity follows a rostro-caudal gradient. Our results provide
      evidence for a novel framework for the intrinsic organization of the frontal
      cortex that incorporates connections between medio-lateral, dorso-ventral, and
      rostro-caudal axes. 

PMID- 22879356
TI  - HPLC and chemometric methods for the simultaneous determination of miconazole
      nitrate and nystatin.
AB  - High-performance liquid chromatography (HPLC) and chemometric methods were
      applied to the simultaneous determination of the two nonsteroidal antifungal
      drugs, miconazole (MIC) and nystatin (NYS). The applied chemometric techniques
      are multivariate methods including classical least squares, principal component
      regression and partial least squares methods. The ultraviolet (UV) absorption
      spectra of the standard solutions of the training and validation sets in methanol
      are recorded in the range of 280-320 nm at 0.2-nm intervals. The HPLC method
      depends on reversed-phase separation using a C18 column. The mobile phase
      consists of a mixture of methanol-acetonitrile-ammonium acetate buffer (pH 6; 50
      mM) (60:30:10 v/v/v). The UV detector was set at 230 nm. The developed methods
      were validated and successfully applied to the simultaneous determination of MIC
      and NYS in their tablets. The assay results obtained using the chemometric
      methods were statistically compared to those of the HPLC method and good
      agreement was observed.

PMID- 22879355
TI  - Functional connection between posterior superior temporal gyrus and ventrolateral
      prefrontal cortex in human.
AB  - The connection between auditory fields of the temporal lobe and prefrontal cortex
      has been well characterized in nonhuman primates. Little is known of
      temporofrontal connectivity in humans, however, due largely to the fact that
      invasive experimental approaches used so successfully to trace anatomical
      pathways in laboratory animals cannot be used in humans. Instead, we used a
      functional tract-tracing method in 12 neurosurgical patients with multicontact
      electrode arrays chronically implanted over the left (n = 7) or right (n = 5)
      perisylvian temporal auditory cortex (area PLST) and the ventrolateral prefrontal
      cortex (VLPFC) of the inferior frontal gyrus (IFG) for diagnosis and treatment of
      medically intractable epilepsy. Area PLST was identified by the distribution of
      average auditory-evoked potentials obtained in response to simple and complex
      sounds. The same sounds evoked little if there is any activity in VLPFC. A single
      bipolar electrical pulse (0.2 ms, charge-balanced) applied between contacts
      within physiologically identified PLST resulted in polyphasic evoked potentials
      clustered in VLPFC, with greatest activation being in pars triangularis of the
      IFG. The average peak latency of the earliest negative deflection of the evoked
      potential on VLPFC was 13.48 ms (range: 9.0-18.5 ms), providing evidence for a
      rapidly conducting pathway between area PLST and VLPFC. 

PMID- 22879357
TI  - The prevalence of prenatal opioid and other drug use in Utah.
AB  - OBJECTIVES: Determine the prevalence of prenatal opioid and other drug positivity
      among women delivering infants in Utah and compare the findings with national
      data. STUDY DESIGN: Umbilical cord tissue samples and nonidentifiable demographic
      data were collected anonymously in 13 labor and delivery units throughout Utah.
      Samples were analyzed for opioids, amphetamines, cannabinoids, cocaine,
      phencyclidine, barbiturates, benzodiazepines, propoxyphene, and alcohol
      biomarkers. RESULTS: Fifty-eight (6.8%) of 850 umbilical cord samples were
      positive for one or more substances. Opioids were the most frequently detected
      drugs (4.7%). Fewer samples were positive for alcohol (0.4%), methamphetamine
      (0.1%), cocaine (0.1%), and marijuana (0.4%). CONCLUSION: Opioids were the most
      frequently detected drugs at delivery. Although some of the samples positive for
      opioids might have been a result of intrapartum exposure, a significant number
      were positive for opioids that are not given during labor. This parallels the
      increasing nonmedical use of prescription pain medications in the general
      population and has important implications for neonates because of the potential
      for significant morbidity secondary to neonatal abstinence syndrome.

PMID- 22879358
TI  - Association between congenital anomalies and area-level deprivation among infants
      in neonatal intensive care units.
AB  - OBJECTIVE: To examine the relationship between area-level material deprivation
      and the risk of congenital anomalies in infants admitted to neonatal intensive
      care units (NICUs) across Canada. STUDY DESIGN: The Canadian Neonatal Network
      database was used to identify admitted infants who had congenital anomalies
      between 2005 and 2009. The association between congenital anomalies and material
      deprivation quintile was assessed using logistic regression analysis. RESULTS: Of
      55,961 infants admitted to participating NICUs during the study period, 6002
      (10.7%) had major, 6244 (11.2%) had minor, and 43,715 (78.1%) had no anomalies.
      There were higher odds of major anomalies (odds ratio [OR] 1.13, 95% confidence
      interval [CI] 1.03 to 1.24) but not minor anomalies (OR 1.01, 95% CI 0.93 to
      1.11) in the highest-deprivation areas as compared with the lowest-deprivation
      area of maternal residence. Analyses of groups of major anomalies revealed higher
      odds for chromosomal (OR 1.48, 95% CI 1.05 to 2.10) and multiple-systems (OR
      1.40, 95% CI 1.14 to 1.71) anomalies in the highest-deprivation areas compared
      with the lowest-deprivation areas. CONCLUSION: There are socioeconomic
      inequalities in the risk of major congenital anomalies, especially chromosomal
      and multiple-systems anomalies, in the NICU population with the highest rates in
      the most socioeconomically deprived areas.

PMID- 22879359
TI  - Six-year prospective audit of 'scoop and run' for chest-reopening after cardiac
      arrest in a cardiac surgical ward setting.
AB  - OBJECTIVES: The aim of the study was to identify which cardiac surgical ward
      patients benefit from 'scoop and run' to the operating room for chest reopening.
      METHODS: In-hospital arrests in a cardiothoracic hospital were prospectively
      audited over a 6-year period. The following pieces of information were collected
      for every patient who was scooped to the operating room following cardiac arrest
      on the postoperative cardiac surgical wards: type of arrest, time since surgery,
      patient physiology before arrest, time to chest reopening, location of chest
      opening, surgical findings on reopening, time to cardiopulmonary bypass (if used)
      and patient outcomes. EXCLUSIONS: arrests in intensive care unit (ICU) and
      operating rooms. The primary outcome measure was survival to discharge from the
      hospital. RESULTS: There were 99 confirmed ward arrests in 97 cardiac surgical
      patients. The overall survival rates to discharge and at 1 year were 53.6% (52 of
      97 patients) and 44.3% (43 of 97 patients), respectively. Twenty-one of the 97
      (21.6%) patients underwent scoop and run to the operating room or ICU. Five of 12
      daytime 'scoop and runs' survived to discharge, whereas none of nine survived
      where scoop and run was undertaken at night (P < 0.05). There was a trend towards
      increased survival when 'scoop and run' was undertaken following ventricular
      fibrillation/pulseless ventricular tachycardia arrests (P = 0.06) and in younger
      patients (P = 0.12) but neither achieved statistical significance. The median
      time out from surgery of survivors was 4 days (range 2-14 days). The median time
      to chest opening in survivors was 22 min. Cardiopulmonary bypass was utilized in
      four of five survivors. The median ICU and hospital lengths of stay were 176 h
      (range 34-857) and 28 days (range 13-70), respectively. CONCLUSIONS: The key
      determinant of a favourable 'scoop and run' outcome was whether the arrest
      occurred during daytime or night-time hours (P < 0.05). Despite a median time to
      chest opening of 22 min, all five survivors were discharged neurologically
      intact. The median time from surgery in these survivors was 4 days. Because of
      the risk of hypoxic brain damage, 'scoop and run' should be restricted to
      patients suffering witnessed arrests. The study has potential implications for
      resuscitation training and out-of-hours medical staffing in cardiothoracic
      hospitals.

PMID- 22879362
TI  - Cohort Profile: the HUNT Study, Norway.
AB  - The HUNT Study includes large total population-based cohorts from the 1980ies,
      covering 125 000 Norwegian participants; HUNT1 (1984-86), HUNT2 (1995-97) and
      HUNT3 (2006-08). The study was primarily set up to address arterial hypertension,
      diabetes, screening of tuberculosis, and quality of life. However, the scope has
      expanded over time. In the latest survey a state of the art biobank was
      established, with availability of biomaterial for decades ahead. The three
      population based surveys now contribute to important knowledge regarding health
      related lifestyle, prevalence and incidence of somatic and mental illness and
      disease, health determinants, and associations between disease phenotypes and
      genotypes. Every citizen of Nord-Trondelag County in Norway being 20 years or
      older, have been invited to all the surveys for adults. Participants may be
      linked in families and followed up longitudinally between the surveys and in
      several national health- and other registers covering the total population. The
      HUNT Study includes data from questionnaires, interviews, clinical measurements
      and biological samples (blood and urine). The questionnaires included questions
      on socioeconomic conditions, health related behaviours, symptoms, illnesses and
      diseases. Data from the HUNT Study are available for researchers who satisfy some
      basic requirements (www.ntnu.edu/hunt), whether affiliated in Norway or abroad. 

PMID- 22879363
TI  - The association of asthma and wheezing with major depressive episodes: an
      analysis of 245 727 women and men from 57 countries.
AB  - BACKGROUND: Epidemiological studies have shown that asthma is positively
      associated with depression. Most of this evidence stems from individual studies
      conducted in Western populations (e.g. Europe, North America and Australia). It
      is still unclear whether such findings generalize to non-Western countries. To
      address this question, the present study investigated the association of asthma
      and wheezing with depression in a large multi-national sample. METHODS: We used
      data from the 2002 World Health Survey. Participants reported physician-diagnosed
      asthma and attacks of wheezing within the past 12 months. Questions on depressive
      symptoms, their duration and persistence were used to define presence of a major
      depressive episode (MDE) within the past 12 months. ORs and 95% CIs were
      estimated by logistic regression for the entire sample, by continent (Australia,
      Europe, South America, Asia and Africa) and by country. Complete information was
      available for 57 countries. RESULTS: Both asthma and wheezing were associated
      with MDE in the entire sample (OR=2.37, 95% CI=2.10-2.66 and OR=3.06, 95% CI=2.75
      3.40, respectively). Similar associations were found for all continents with
      generally stronger ORs in South America, Asia and Africa for both asthma (ORs >=
      1.8) and wheezing (ORs  >= 2.8). On the country level, wheezing showed a
      consistent pattern of association with MDE. Similar patterns were found for
      asthma. CONCLUSIONS: Despite a range of country differences that could affect the
      association of asthma with depression, such as access to health care, the results
      of this study indicate that the co-occurrence of asthma and depression is a
      universal phenomenon.

PMID- 22879365
TI  - Informatics 2.0: implications of social media, mobile health, and patient
      reported outcomes for healthcare and individual privacy.

PMID- 22879364
TI  - Discordant cellular response to presurgical letrozole in bilateral synchronous
      ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification.
AB  - We describe herein a patient presenting with bilateral estrogen-receptor-positive
      (ER+) breast tumors who was enrolled in a clinical trial exploring molecular
      aberrations associated with hormone-refractory tumor cell proliferation. Short
      term (two week) hormonal therapy with the aromatase inhibitor letrozole
      substantially reduced proliferation as measured by Ki67 immunohistochemistry in
      one tumor, whereas the second was essentially unchanged. Extensive molecular and
      genetic work-up of the two tumors yielded divergent lesions in the two tumors: an
      activating KRAS mutation in the responsive tumor and an amplification of the
      fibroblast growth factor receptor-1 (FGFR1) locus in the treatment-refractory
      tumor. These findings provide an insight to possible mechanisms of resistance to
      antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity
      of clinically approved assays to identify FGFR1 gene amplification, which occur
      in approximately 5% of breast tumors and have been linked to antiestrogen
      resistance. It is quite possible that the addition of FGFR inhibitors to ER
      targeted therapy will yield a superior antitumor effect and improved patient
      outcome. Second, they suggest that the role of activating mutations in RAS,
      although rare in breast cancer, may need to be explored in the context of ER+
      breast tumors.

PMID- 22879366
TI  - President's column: two important decisions, one clear direction...

PMID- 22879367
TI  - Cardiovascular risk of high- versus moderate-intensity aerobic exercise in
      coronary heart disease patients.
AB  - BACKGROUND: Exercise performed at higher relative intensities has been found to
      elicit a greater increase in aerobic capacity and greater cardioprotective
      effects than exercise at moderate intensities. An inverse association has also
      been detected between the relative intensity of physical activity and the risk of
      developing coronary heart disease, independent of the total volume of physical
      activity. Despite that higher levels of physical activity are effective in
      reducing cardiovascular events, it is also advocated that vigorous exercise could
      acutely and transiently increase the risk of sudden cardiac death and myocardial
      infarction in susceptible persons. This issue may affect cardiac rehabilitation.
      METHODS AND RESULTS: We examined the risk of cardiovascular events during
      organized high-intensity interval exercise training and moderate-intensity
      training among 4846 patients with coronary heart disease in 3 Norwegian cardiac
      rehabilitation centers. In a total of 175 820 exercise training hours during
      which all patients performed both types of training, we found 1 fatal cardiac
      arrest during moderate-intensity exercise (129 456 exercise hours) and 2 nonfatal
      cardiac arrests during high-intensity interval exercise (46 364 exercise hours).
      There were no myocardial infarctions in the data material. Because the number of
      high-intensity training hours was 36% of the number of moderate-intensity hours,
      the rates of complications to the number of patient-exercise hours were 1 per 129
      456 hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity
      exercise. CONCLUSIONS: The results of the current study indicate that the risk of
      a cardiovascular event is low after both high-intensity exercise and moderate
      intensity exercise in a cardiovascular rehabilitation setting. Considering the
      significant cardiovascular adaptations associated with high-intensity exercise,
      such exercise should be considered among patients with coronary heart disease.

PMID- 22879368
TI  - Swing and a miss or inside-the-park home run: which fate awaits high-intensity
      exercise training?

PMID- 22879369
TI  - A pilot study examining the severity and outcome of the post-cardiac arrest
      syndrome: a comparative analysis of two geographically distinct hospitals.
AB  - BACKGROUND: Cardiac arrest occurs in >400 000 patients in the United States per
      year, and mortality rates vary across the country. Whether variations in cardiac
      arrest outcome are the result of differences in hospital or patient
      characteristics remains understudied. We tested whether hospital-independent
      factors would account for the difference in outcome between 2 geographically
      distinct hospitals. METHODS AND RESULTS: Consecutive adult (age >18 years) out-of
      hospital cardiac arrests were considered for analysis. The primary outcome was in
      hospital mortality. Predictor variables were classified according to whether they
      were hospital-independent or whether they could be related to the hospital's
      quality of care. Only hospital-independent variables were considered for the
      analysis. Sequential logistic modeling was used to assess outcome. A propensity
      score was derived and was used in subsequent multivariate logistic regression to
      predict hospital outcome. A total of 208 subjects were included. Overall
      mortality in the Detroit cohort was 87% in comparison with 61% in the Boston
      cohort (odds ratio: 4.4; 95% confidence interval: 2.2-8.8). After sequential
      adjustments for baseline covariates, out-of-hospital cardiac arrest score and
      propensity score, city was not significantly associated with mortality (odds
      ratio: 1.16; 95% confidence interval: 0.45-2.97). After propensity matching there
      was no significant difference in the odds ratio for death between the 2 cities
      (odds ratio: 1.15; 95% confidence interval: 0.51-2.61). CONCLUSIONS: In this
      pilot study, we found that pre- and intra-arrest conditions contribute
      substantially to the severity of the postarrest syndrome and on outcomes.
      Postarrest quality-of-care evaluations should include inherent differences in the
      presenting syndrome rather than a crude mortality rate.

PMID- 22879370
TI  - Targeting mannose-binding lectin confers long-lasting protection with a
      surprisingly wide therapeutic window in cerebral ischemia.
AB  - BACKGROUND: The involvement of the complement system in brain injury has been
      scarcely investigated. Here, we document the pivotal role of mannose-binding
      lectin (MBL), one of the recognition molecules of the lectin complement pathway,
      in brain ischemic injury. METHODS AND RESULTS: Focal cerebral ischemia was
      induced in mice (by permanent or transient middle cerebral artery occlusion) and
      rats (by 3-vessel occlusion). We first observed that MBL is deposited on ischemic
      vessels up to 48 hours after injury and that functional MBL/MBL-associated serine
      protease 2 complexes are increased. Next, we demonstrated that (1) MBL(-/-) mice
      are protected from both transient and permanent ischemic injury; (2) Polyman2,
      the newly synthesized mannosylated molecule selected for its binding to MBL,
      improves neurological deficits and infarct volume when given up to 24 hours after
      ischemia in mice; (3) anti-MBL-A antibody improves neurological deficits and
      infarct volume when given up to 18 hours after ischemia, as assessed after 28
      days in rats. CONCLUSIONS: Our data show an important role for MBL in the
      pathogenesis of brain ischemic injury and provide a strong support to the concept
      that MBL inhibition may be a relevant therapeutic target in humans, one with a
      wide therapeutic window of application.

PMID- 22879371
TI  - Aortic regurgitation quantification using cardiovascular magnetic resonance:
      association with clinical outcome.
AB  - BACKGROUND: Current indications for surgery in patients with significant aortic
      regurgitation (AR) focus on symptoms and left ventricular dilation/dysfunction.
      However, prognosis is already reduced by this stage, and earlier identification
      of patients for surgery could be beneficial. Quantifying the regurgitation may
      help, but there are limited data on its link with outcome. Cardiovascular
      magnetic resonance (CMR) can accurately quantify AR, and we examined whether this
      was associated with the future need for surgery. METHODS AND RESULTS: One hundred
      thirteen patients with echocardiographic moderate or severe AR were monitored for
      up to 9 years (mean 2.6 +/- 2.1 years) following a CMR scan, and the progression
      to symptoms or other indications for surgery was monitored. AR quantification
      identified outcome with high accuracy: 85% of the 39 subjects with regurgitant
      fraction >33% progressed to surgery (mostly within 3 years) in comparison with 8%
      of 74 subjects with regurgitant fraction <= 33% (P<0.0001); the area under the
      curve on receiver operating characteristic analysis was 0.93 (P<0.0001). This
      ability remained strong on time-dependent Kaplan-Meier survival curves. CMR
      derived left ventricular end-diastolic volume >246 mL had good, although lower,
      discriminatory ability (area under the curve 0.88), but the combination of this
      measure with regurgitant fraction provided the best discriminatory power.
      CONCLUSIONS: High degrees of CMR-quantified AR were associated with the
      development of symptoms or other indications for surgery. Quantifying AR showed
      slightly better discriminatory ability than "gold standard" CMR ventricular
      volume assessment. This could provide a new paradigm for the timing of surgical
      intervention but requires confirmation in a clinical trial.

PMID- 22879372
TI  - Development of an instrument to measure face validity, feasibility and utility of
      patient questionnaire use during health care: the QQ-10.
AB  - OBJECTIVE: To develop and establish the psychometric properties of an instrument
      to measure face validity, feasibility and utility of patient questionnaires used
      during health care. DESIGN: Our instrument, QQ-10, is a 10-item self-completed
      questionnaire, which was developed during the evaluation of another questionnaire
      (ePAQ-PF), to assess patients' views on questionnaire use during health care.
      SETTING: Urogynaecology Department, Royal Hallamshire Hospital, Sheffield, UK.
      PARTICIPANTS: The Sheffield maternity patient user group identified 10 key themes
      relating to patients' views on using questionnaires; these themes translated into
      10 statements, each using the same 5-point Likert response scale. INTERVENTION:
      Not applicable. Outcome Measures Principal component analysis established the
      factor structure of our instrument. Internal reliability was assessed using
      Cronbach's alpha. Construct validity was assessed using Spearman's rho. RESULTS:
      Factor analysis yielded two meaningful factors: Value and Burden, both achieving
      Cronbach's alpha scores >0.7. Significant correlations were found between scores
      for Value and communication experience and between scores for Burden and barriers
      to health care. CONCLUSIONS: Our instrument offers a valid, reliable measure of
      patients' views relating to value and burden of using health-related quality of
      life questionnaires. Its two domains show good internal reliability and with its
      free text items, it may offer a valuable, standardized assessment of face
      validity and utility of other questionnaires used in health care.

PMID- 22879373
TI  - Reliability and accuracy of the screening for adverse events in Brazilian
      hospitals.
AB  - OBJECTIVE: To analyze the reliability and accuracy of the screening for adverse
      events (AEs) conducted by nurses taking the assessment by medical residents as
      the reference. DESIGN: A validation study of the screening phase of a previous
      retrospective cohort study based on the patient record review that estimated the
      incidence of AEs (base study). SETTING: Three general teaching hospitals in the
      State of Rio de Janeiro, Brazil. PARTICIPANTS: A subsample of 242 medical records
      randomly selected from an original sample of 1103 previously evaluated records.
      MAIN OUTCOME MEASURE(S): A two-step approach was used for analysis: the
      identification of at least one screening criterion (first endpoint) and the
      validation of each identified criterion (second endpoint), taking the assessment
      by medical residents as the reference. Kappa coefficient; simple percentage
      agreement; sensitivity; specificity; positive and negative predictive values were
      calculated. RESULTS: The total agreement between medical residents and nurses on
      the presence of screening criteria was moderate (78.9%, K = 0.55). Specificity
      (81.6%) was higher than sensitivity (74.4%). Nurses detected more screening
      criteria that were later confirmed as true AEs (179 vs. 171, respectively).
      Significant differences in the detection of the screening criteria: 'Other
      complications', 'Hospitalization injury' and 'Prior admission' were observed.
      CONCLUSION: The results suggested a good performance of the nurses in the
      screening for detection of AE and showed significant differences in relation to
      detection of specific screening criteria among reviewers. A better understanding
      of the screening process and the performance of reviewers was provided.

PMID- 22879374
TI  - Learning from large-scale quality improvement through comparisons.
AB  - OBJECTIVE: To discover lessons from 10 national health and social care quality
      programmes in the Netherlands. DESIGN: A mixed-methods comparison using a
      'quantitative summarization of evidence for systematic comparison'. Each research
      team assessed whether there was evidence from their evaluation to support or
      refute 17 hypotheses about successful implementation of quality programmes. The
      programme managers carried out a similar assessment. Their assessments were
      represented as scores which made it possible to carry out a cross-case analysis
      to assess factors affecting the success of large-scale quality programmes.
      PARTICIPANTS: The researchers who evaluated each of the programmes and the
      leaders who organized each programme. SETTING: Health and social care service
      organizations and national organization, which led the quality improvement
      programmes. INTERVENTION(S): This study did not make an intervention but compared
      experiences and evaluations of interventions carried out by national organization
      to health and social care service organizations to help these organizations to
      improve their services. MAIN OUTCOME MEASURE(S): The success of the national
      programmes, and the learning achieved by the programme organizations and care
      service delivery organizations. RESULTS: The method provided a way to summarize
      and compare complex information. Common factors which appeared to influence
      success in implementation included understanding of political processes, leader's
      influencing skills, as well as technical skills to manage projects and apply
      improvement and change methods. CONCLUSIONS: Others could use a similar method to
      make a fast, broad level, but systematic comparison across reports of
      improvements or programmes. Descriptions, and then comparisons of the programmes,
      reveal common factors which appeared to influence success in implementation.
      There were groups of factors which appeared to be more important for the success
      of certain types of programmes. It is possible that these factors may also be
      important for the success of large-scale improvement programmes in other
      countries.

PMID- 22879375
TI  - Discovery of multi-dimensional modules by integrative analysis of cancer genomic
      data.
AB  - Recent technology has made it possible to simultaneously perform multi-platform
      genomic profiling (e.g. DNA methylation (DM) and gene expression (GE)) of
      biological samples, resulting in so-called 'multi-dimensional genomic data'. Such
      data provide unique opportunities to study the coordination between regulatory
      mechanisms on multiple levels. However, integrative analysis of multi-dimensional
      genomics data for the discovery of combinatorial patterns is currently lacking.
      Here, we adopt a joint matrix factorization technique to address this challenge.
      This method projects multiple types of genomic data onto a common coordinate
      system, in which heterogeneous variables weighted highly in the same projected
      direction form a multi-dimensional module (md-module). Genomic variables in such
      modules are characterized by significant correlations and likely functional
      associations. We applied this method to the DM, GE, and microRNA expression data
      of 385 ovarian cancer samples from the The Cancer Genome Atlas project. These md
      modules revealed perturbed pathways that would have been overlooked with only a
      single type of data, uncovered associations between different layers of cellular
      activities and allowed the identification of clinically distinct patient
      subgroups. Our study provides an useful protocol for uncovering hidden patterns
      and their biological implications in multi-dimensional 'omic' data.

PMID- 22879376
TI  - 3D chromatin conformation correlates with replication timing and is conserved in
      resting cells.
AB  - Although chromatin folding is known to be of functional importance to control the
      gene expression program, less is known regarding its interplay with DNA
      replication. Here, using Circular Chromatin Conformation Capture combined with
      high-throughput sequencing, we identified megabase-sized self-interacting domains
      in the nucleus of a human lymphoblastoid cell line, as well as in cycling and
      resting peripheral blood mononuclear cells (PBMC). Strikingly, the boundaries of
      those domains coincide with early-initiation zones in every cell types.
      Preferential interactions have been observed between the consecutive early
      initiation zones, but also between those separated by several tens of megabases.
      Thus, the 3D conformation of chromatin is strongly correlated with the
      replication timing along the whole chromosome. We furthermore provide direct
      clues that, in addition to the timing value per se, the shape of the timing
      profile at a given locus defines its set of genomic contacts. As this timing
      related scheme of chromatin organization exists in lymphoblastoid cells, resting
      and cycling PBMC, this indicates that it is maintained several weeks or months
      after the previous S-phase. Lastly, our work highlights that the major chromatin
      changes accompanying PBMC entry into cell cycle occur while keeping largely
      unchanged the long-range chromatin contacts.

PMID- 22879377
TI  - Characterization of CRISPR RNA processing in Clostridium thermocellum and
      Methanococcus maripaludis.
AB  - The CRISPR arrays found in many bacteria and most archaea are transcribed into a
      long precursor RNA that is processed into small clustered regularly interspaced
      short palindromic repeats (CRISPR) RNAs (crRNAs). These RNA molecules can contain
      fragments of viral genomes and mediate, together with a set of CRISPR-associated
      (Cas) proteins, the prokaryotic immunity against viral attacks. CRISPR/Cas
      systems are diverse and the Cas6 enzymes that process crRNAs vary between
      different subtypes. We analysed CRISPR/Cas subtype I-B and present the
      identification of novel Cas6 enzymes from the bacterial and archaeal model
      organisms Clostridium thermocellum and Methanococcus maripaludis C5.
      Methanococcus maripaludis Cas6b in vitro activity and specificity was determined.
      Two complementary catalytic histidine residues were identified. RNA-Seq analyses
      revealed in vivo crRNA processing sites, crRNA abundance and orientation of
      CRISPR transcription within these two organisms. Individual spacer sequences were
      identified with strong effects on transcription and processing patterns of a
      CRISPR cluster. These effects will need to be considered for the application of
      CRISPR clusters that are designed to produce synthetic crRNAs.

PMID- 22879378
TI  - Fluorescent signatures for variable DNA sequences.
AB  - Life abounds with genetic variations writ in sequences that are often only a few
      hundred nucleotides long. Rapid detection of these variations for identification
      of genetic diseases, pathogens and organisms has become the mainstay of molecular
      science and medicine. This report describes a new, highly informative closed-tube
      polymerase chain reaction (PCR) strategy for analysis of both known and unknown
      sequence variations. It combines efficient quantitative amplification of single
      stranded DNA targets through LATE-PCR with sets of Lights-On/Lights-Off probes
      that hybridize to their target sequences over a broad temperature range.
      Contiguous pairs of Lights-On/Lights-Off probes of the same fluorescent color are
      used to scan hundreds of nucleotides for the presence of mutations. Sets of
      probes in different colors can be combined in the same tube to analyze even
      longer single-stranded targets. Each set of hybridized Lights-On/Lights-Off
      probes generates a composite fluorescent contour, which is mathematically
      converted to a sequence-specific fluorescent signature. The versatility and broad
      utility of this new technology is illustrated in this report by characterization
      of variant sequences in three different DNA targets: the rpoB gene of
      Mycobacterium tuberculosis, a sequence in the mitochondrial cytochrome C oxidase
      subunit 1 gene of nematodes and the V3 hypervariable region of the bacterial 16 s
      ribosomal RNA gene. We anticipate widespread use of these technologies for
      diagnostics, species identification and basic research.

PMID- 22879379
TI  - Inducible and reversible regulation of endogenous gene in mouse.
AB  - Methods for generating loss-of-function mutations, such as conventional or
      conditional gene knockout, are widely used in deciphering gene function in vivo.
      By contrast, inducible and reversible regulation of endogenous gene expression
      has not been well established. Using a mouse model, we demonstrate that a
      chimeric transcriptional repressor molecule (tTS) can reversibly inhibit the
      expression of an endogenous gene, Nmyc. In this system, a tetracycline response
      element (TRE) artificially inserted near the target gene's promoter region turns
      the gene on and off in a tetracycline-inducible manner. Nmyc(TRE) mice were
      generated by inserting a TRE into the first intron of Nmyc by the knockin
      technique. Nmyc(TRE) mice were crossed to tTS transgenic mice to produce
      Nmyc(TRE/TRE): tTS embryos. In these embryos, tTS blocked Nmyc expression, and
      embryonic lethality was observed at E11.5d. When the dam was exposed to drinking
      water containing doxycycline (dox), normal endogenous Nmyc expression was
      rescued, and the embryo survived to birth. This novel genetic modification
      strategy based on the tTS-dox system for inducible and reversible regulation of
      endogenous mouse genes will be a powerful tool to investigate target genes that
      cause embryonic lethality or other defects where reversible regulation or
      temporary shutdown of the target gene is needed.

PMID- 22879381
TI  - Establishment of single-cell screening system for the rapid identification of
      transcriptional modulators involved in direct cell reprogramming.
AB  - Combinatorial interactions of transcription modulators are critical to regulate
      cell-specific expression and to drive direct cell reprogramming (e.g. trans
      differentiation). However, the identification of key transcription modulators
      from myriad of candidate genes is laborious and time consuming. To rapidly
      identify key regulatory factors involved in direct cell reprogramming, we
      established a multiplex single-cell screening system using a fibroblast-to
      monocyte transition model. The system implements a single-cell 'shotgun
      transduction' strategy followed by nested-single-cell-polymerase chain reaction
      (Nesc-PCR) gene expression analysis. To demonstrate this, we simultaneously
      transduced 18 monocyte-enriched transcription modulators in fibroblasts followed
      by selection of single cells expressing monocyte-specific CD14 and HLA-DR cell
      surface markers from a heterogeneous population. Highly multiplex Nesc-PCR
      expression analysis revealed a variety of gene combinations with a significant
      enrichment of SPI1 (86/86) and a novel transcriptional modulator, HCLS1 (76/86),
      in the CD14(+)/HLA-DR(+) single cells. We could further demonstrate the
      synergistic role of HCLS1 in regulating monocyte-specific gene expressions and
      phagocytosis in dermal fibroblasts in the presence of SPI1. This study
      establishes a platform for a multiplex single-cell screening of combinatorial
      transcription modulators to drive any direct cell reprogramming.

PMID- 22879382
TI  - Signaling pathways for fission yeast sexual differentiation at a glance.

PMID- 22879380
TI  - Structure of the RNA claw of the DNA packaging motor of bacteriophage Phi29.
AB  - Bacteriophage DNA packaging motors translocate their genomic DNA into viral
      heads, compacting it to near-crystalline density. The Bacillus subtilis phage 29
      has a unique ring of RNA (pRNA) that is an essential component of its motor,
      serving as a scaffold for the packaging ATPase. Previously, deletion of a three
      base bulge (18-CCA-20) in the pRNA A-helix was shown to abolish packaging
      activity. Here, we solved the structure of this crucial bulge by nuclear magnetic
      resonance (NMR) using a 27mer RNA fragment containing the bulge (27b). The bulge
      actually involves five nucleotides (17-UCCA-20 and A100), as U17 and A100 are not
      base paired as predicted. Mutational analysis showed these newly identified bulge
      residues are important for DNA packaging. The bulge introduces a 33-35 degrees 
      bend in the helical axis, and inter-helical motion around this bend appears to be
      restricted. A model of the functional 120b pRNA was generated using a 27b NMR
      structure and the crystal structure of the 66b prohead-binding domain. Fitting
      this model into a cryo-EM map generated a pentameric pRNA structure; five helices
      projecting from the pRNA ring resemble an RNA claw. Biochemical analysis
      suggested that this shape is important for coordinated motor action required for
      DNA translocation.

PMID- 22879383
TI  - Aryl hydrocarbon receptor (AHR)-active pharmaceuticals are selective AHR
      modulators in MDA-MB-468 and BT474 breast cancer cells.
AB  - Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4
      hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as
      aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models.
      In this study, the eight AHR-active pharmaceuticals were investigated in highly
      aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer
      cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1
      (mRNA), and cell migration were determined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin
      (TCDD) was used as a positive control. The AHR agonist activities of the
      pharmaceuticals depended on structure, response, and cell context. Most compounds
      induced one or more AHR-mediated responses in BT474 cells, whereas in Ah
      responsive MDA-MB-468 cells effects of the AHR-active pharmaceuticals were highly
      variable. 4-Hydroxytamoxifen, mexiletine, and tranilast did not induce CYP1A1 in
      MDA-MB-468 cells; moreover, in combination with TCDD, mexiletine was a potent AHR
      antagonist, tranilast was a partial antagonist, and 4-hydroxytamoxifen also
      exhibited some AHR antagonist activity. Omeprazole and, to a lesser extent,
      sulindac and leflunomide were full and partial AHR agonists, respectively, in
      both breast cancer cell lines. These data indicate that the AHR-active
      pharmaceuticals are selective AHR modulators, and applications of these drugs for
      targeting the AHR must be confirmed by studies using the most relevant cell
      context.

PMID- 22879384
TI  - Late sodium current inhibition alone with ranolazine is sufficient to reduce
      ischemia- and cardiac glycoside-induced calcium overload and contractile
      dysfunction mediated by reverse-mode sodium/calcium exchange.
AB  - Excessive reverse-mode (RM) sodium/calcium exchanger 1.1 (NCX1.1) activity,
      resulting from intracellular sodium accumulation caused by reduced Na+/K+-ATPase
      activity, increased Na-H exchanger 1 activity. The induction of the voltage-gated
      sodium channel late current component (late INa), is a major pathway for
      intracellular calcium (Ca2+i) loading in cardiac ischemia-reperfusion (IR) injury
      and cardiac glycoside toxicity. Inhibition of late INa with the antianginal agent
      ranolazine is protective in models of IR injury and cardiac glycoside toxicity.
      However, whether inhibition of late INa alone is sufficient to provide maximal
      protection or additional inhibition of RM NCX1.1 provides further benefit remains
      to be determined conclusively. Therefore, the effects of ranolazine were compared
      with the INa inhibitor lidocaine in models of IR injury and ouabain toxicity, RM
      NCX1.1-mediated Ca2+ overload, and patch-clamp assays of RM NCX1.1 currents.
      Ranolazine and lidocaine (10 MUM) similarly reduced Ca2+i overload and improved
      left ventricle work recovery in whole-heart models of IR injury or exposure to
      ouabain (80 MUM). Ranolazine (10 MUM), but not lidocaine (10 MUM), reduced RM
      NCX1.1-mediated Ca2+i overload in ventricular myocytes. Furthermore, ranolazine
      inhibited RM NCX1.1 currents (IC50 1.7 MUM), without affecting forward mode
      currents, revealing that ranolazine has novel RM NCX1.1 inhibitory actions.
      However, because lidocaine provides similar protection to ranolazine in whole
      heart models but does not inhibit RM NCX1.1, we conclude that induction of late
      INa is upstream of RM NCX1.1 activity and selective inhibition of late INa alone
      is sufficient to reduce Ca2+i overload and contractile dysfunction in IR injury
      and cardiac glycoside toxicity.

PMID- 22879385
TI  - A multicenter phase II study of single-agent enzastaurin in previously treated
      Waldenstrom macroglobulinemia.
AB  - PURPOSE: Enzastaurin is a serine/threonine kinase inhibitor that showed
      antiangiogenic, antiproliferative, and proapoptotic properties in vitro and
      antitumor activity in vivo in a xenograft Waldenstrom macroglobulinemia (WM)
      model. These findings provided the rationale for a multicenter phase II trial of
      oral enzastaurin in previously treated patients with WM. EXPERIMENTAL DESIGN:
      Patients who were treated with 1 to 5 prior regimens and who had a baseline
      immunoglobulin M level 2 times or more the upper limit of normal received oral
      enzastaurin 250 mg twice daily (500 mg total) after a single loading dose (day 1,
      cycle 1) of 375 mg 3 times daily (1,125 mg total) for 8 cycles of 28 days each or
      until progressive disease. Six patients who progressed during treatment with
      enzastaurin had dexamethasone added per protocol. RESULTS: From July 2008 to
      December 2010, 42 patients were enrolled. The objective response rate (RR) was
      38.1% (2 partial and 14 minor responses). One patient had grade 3 leukopenia and
      one patient died during the study from septic shock; both events were considered
      drug related. A statistically significant association between RR and interleukin
      15 (IL-15) was observed, suggesting that higher concentration levels of IL-15 may
      be associated with better response. CONCLUSION: Enzastaurin was active and well
      tolerated in previously treated patients with WM. Because of the small sample
      size of this uncontrolled study, further assessment of the relationship between
      IL-15 and response to enzastaurin in patients with WM is required. These results
      warrant further investigation of enzastaurin for the treatment of WM.

PMID- 22879386
TI  - LAP+CD4+ T cells are suppressors accumulated in the tumor sites and associated
      with the progression of colorectal cancer.
AB  - PURPOSE: Suppressor T cells are one of the determinants of colorectal cancer
      (CRC) clinical outcome. LAP(+)CD4(+) T cell is a recently identified subset of
      suppressor T cells. This study was designed to investigate their clinical
      relevance in patients with CRC. EXPERIMENTAL DESIGN: Sixty patients with CRC and
      24 healthy donors (HD) were enrolled in this study. The percentages of
      LAP(+)CD4(+) T cells in peripheral blood and tumor tissue were measured. The
      phenotype and functional relevance of LAP(+)CD4(+) T cells were analyzed
      subsequently. RESULTS: The percentages of LAP(+)CD4(+) T cells in peripheral
      blood of patients with CRC were significantly higher than HD (HD vs. CRC: 3.1% +/
      0.78% vs. 8.8% +/- 5.8%, P < 0.0001) and in tumor tissue when compared with
      nontumor tissue (nontumor vs. tumor: 3.2% +/- 1.1% vs. 9.5% +/- 5.5%, P =
      0.0002). In addition, LAP(+)CD4(+) T cells with effector memory (EM) phenotype
      were more likely to accumulate in the tumor sites than in peripheral blood. These
      LAP(+)CD4(+) T cells produced significantly higher levels of IFN-gamma, IL-17 and
      comparatively lower IL-2 and very few IL-10. LAP(+)CD4(+) T cells could suppress
      the proliferation of LAP(-)CD4(+) T cells that were partially mediated by TGF
      beta. Furthermore, these LAP(+)CD4(+) T cells accumulated in tumor site and
      increased further in the peripheral blood in patients with metastasis.
      CONCLUSIONS: LAP(+)CD4(+) T cells as a suppressor subset could accumulate in the
      tumor microenvironment and circulated more in the peripheral blood with tumor
      progression in patients with CRC.

PMID- 22879387
TI  - Molecular pathways: VCAM-1 as a potential therapeutic target in metastasis.
AB  - Interactions between disseminated tumor cells (DTC) and stromal cells in the
      microenvironment are critical for tumor colonization of distal organs. Recent
      studies have shown that vascular cell adhesion molecule-1 (VCAM-1) is aberrantly
      expressed in breast cancer cells and mediates prometastatic tumor-stromal
      interactions. Moreover, the usefulness of VCAM-1 to DTCs in 2 different organs-
      lung and bone--is based on distinct mechanisms. In the lungs, VCAM-1 on the
      surface of cancer cells binds to its counterreceptor, the alpha4beta1 integrin
      (also known as very-late antigen, VLA-4), on metastasis-associated macrophages,
      triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and
      survival pathway in the cancer cells. In the bone marrow, cancer cell VCAM-1
      attracts and tethers alpha4 integrin-expressing osteoclast progenitors to
      facilitate their maturation into multinucleated osteoclasts that mediate
      osteolytic metastasis. These findings highlight the importance of direct
      interactions between DTCs and stromal cells during tumor dissemination and draw
      attention to the possibility of targeting the alpha4 integrin-VCAM-1 interactions
      in metastatic breast cancer. Anti-alpha4 integrin inhibitors have been developed
      to treat various diseases driven by massive leukocyte infiltrates and have gained
      U.S. Food and Drug Administration approval or are undergoing clinical trials.
      Testing these drugs against tumor-stromal leukocyte interactions may provide a
      new strategy to suppress lung and bone relapse of breast cancer.

PMID- 22879388
TI  - EWS-FLI-1-targeted cytotoxic T-cell killing of multiple tumor types belonging to
      the Ewing sarcoma family of tumors.
AB  - PURPOSE: The Ewing sarcoma family of tumors (ESFT) comprises a group of
      aggressive, malignant bone, and soft tissue tumors that predominantly affect
      children and young adults. These tumors frequently share expression of the EWS
      FLI-1 translocation, which is central to tumor survival but not present in
      healthy cells. In this study, we examined EWS-FLI-1 antigens for their capacity
      to induce immunity against a range of ESFT types. DESIGN: Computer prediction
      analysis of peptide binding, HLA-A2.1 stabilization assays, and induction of
      cytotoxic T-lymphocytes (CTL) in immunized HLA-A2.1 transgenic mice were used to
      assess the immunogenicity of native and modified peptides derived from the fusion
      region of EWS-FLI-1 type 1. CTL-killing of multiple ESFT family members in vitro,
      and control of established xenografts in vivo, was assessed. We also examined
      whether these peptides could induce human CTLs in vitro. RESULTS: EWS-FLI-1 type
      1 peptides were unable to stabilize cell surface HLA-A2.1 and induced weak CTL
      activity against Ewing sarcoma cells. In contrast, peptides with modified anchor
      residues induced potent CTL killing of Ewing sarcoma cells presenting endogenous
      (native) peptides. The adoptive transfer of CTL specific for the modified peptide
      YLNPSVDSV resulted in enhanced survival of mice with established Ewing sarcoma
      xenografts. YLNPSVDSV-specific CTL displayed potent killing of multiple ESFT
      types in vitro: Ewing sarcoma, pPNET, Askin's Tumor, and Biphenotypic sarcoma.
      Stimulation of human peripheral blood mononuclear cells with YLNPSVDSV peptide
      resulted in potent CTL-killing. CONCLUSIONS: These data show that YLNPSVDSV
      peptide is a promising antigen for ESFT immunotherapy and warrants further
      clinical development.

PMID- 22879389
TI  - Counteracting autophagy overcomes resistance to everolimus in mantle cell
      lymphoma.
AB  - PURPOSE: Mantle cell lymphoma (MCL) is an aggressive B-lymphoid neoplasm with
      poor response to conventional chemotherapy and short survival. The
      phosphatidylinositol 3-kinase/Akt/mTOR survival pathway is constitutively
      activated in MCL cells, thereby making the mTOR inhibition an attractive
      therapeutic strategy. The first clinical studies of everolimus (RAD001), an mTOR
      inhibitor, in relapsed MCL patients have reported a significant response. Our aim
      was to analyze the mechanism related to everolimus resistance/sensitivity in MCL
      cells. EXPERIMENTAL DESIGN: Sensitivity to everolimus was analyzed in MCL cell
      lines and primary MCL cells. Everolimus mechanism of action was determined by
      flow cytometry and Western blot. Particularly, autophagy was studied by LC3BI/II
      expression, autophagolysosomes detection by flow cytometry and fluorescence
      microscopy, and siRNA-mediated gene silencing. RESULTS: Everolimus exerted
      antitumoral effect on MCL cells while sparing normal cells. In MCL cell lines,
      this phenomenon was associated to G(1) cell-cycle arrest, dephosphorylation of
      the mTOR downstream targets, 4E-BP1 and S6RP, and rephosphorylation of Akt. A
      synergistic cytotoxic effect was observed between everolimus and an Akt
      inhibitor, which overcame the compensatory reactivation within the mTOR signaling
      pathway. Interestingly, MCL cells with low response to this combination showed
      high levels of autophagy. Accordingly, selective triple knockdown of the
      autophagy genes ATG7, ATG5 and ATG3, and pretreatment with the autophagy
      inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt/mTOR
      inhibitors, leading to the activation of the mitochondrial apoptotic pathway.
      CONCLUSIONS: These results suggest that autophagy induction protects MCL cells
      from Akt/mTOR targeting and counteracting autophagy may represent an attractive
      strategy for sensitizing MCL cells to everolimus-based therapy.

PMID- 22879390
TI  - Fostering the ability of patients to self-manage their CKD.

PMID- 22879391
TI  - Two new large deletions of the AVPR2 gene causing nephrogenic diabetes insipidus
      and a review of previously published deletions.
AB  - BACKGROUND: In this paper, we report two new original deletions and present an
      extended review of the previously characterized AVPR2 gene deletions to better
      understand the underlying deletion mechanisms. METHODS: The two novel deletions
      were defined using polymerase chain reaction mapping and junction fragment
      sequencing. Bioinformatic analysis was performed on both the previously mapped
      deletions and the novel ones through several web tools. RESULTS: In our two
      patients with nephrogenic diabetes insipidus, we found a 23 755 bp deletion and a
      9264 bp deletion both comprising the entire AVPR2 gene and part of the ARHGAP4
      gene. Through bioinformatic studies, the smallest overlapping region as well as
      several motifs and repeats that are known to promote rearrangements were
      confirmed. CONCLUSIONS: Through this study, it was determined that the deletion
      mechanisms in the AVPR2 region do not follow the rules of non-allelic homologous
      recombination. Two of the 13 deletions can be attributed to the fork stalling and
      template switching (FoSTeS) mechanism, whereas the remaining 11 deletions could
      be caused either by non-homologous end joining or by the FoSTeS mechanism.
      Although no recurrence was found, several groupings of deletion breakpoints were
      identified.

PMID- 22879392
TI  - The closer the shield, the higher the score: timing of resistance index
      measurement and its prognostic impact in kidney transplant recipients.

PMID- 22879393
TI  - Comparison of the SF-36 Five-item Mental Health Inventory and Beck Depression
      Inventory for the screening of depressive symptoms in chronic dialysis patients.
AB  - BACKGROUND: The Beck Depression Inventory (BDI) is a standard and validated
      questionnaire to screen for depressive symptoms in chronic dialysis patients, but
      is relatively extensive to use repeatedly in clinical practice. We investigated
      whether the five-item Mental Health Inventory (MHI-5) of the 36-item Short-Form
      Health Survey Questionnaire (SF-36) could be applied to screen for depressive
      symptoms in dialysis patients. Moreover, we determined the optimal MHI-5 cut-off
      score to assess depressive symptoms. METHODS: Chronic dialysis patients from
      three centres filled out the SF-36 and the BDI. A receiver operating
      characteristic (ROC) curve was constructed for the MHI-5 score with BDI >= 16 as
      reference standard to (i) calculate the area under the curve to determine whether
      the MHI-5 could be considered as a useful screening instrument for depressive
      symptoms and (ii) proxy the optimal cut-off score of the MHI-5 to assess
      depressive symptoms. The optimal cut-off score was determined by the value for
      which the sum of sensitivity and specificity had an optimum. RESULTS: Of 133
      included patients, 23% had depressive symptoms as determined with BDI >= 16. The
      correlation of the BDI with MHI-5 was -0.64. The area under the ROC curve was
      0.82 (95% confidence interval 0.74-0.90). The optimal cut-off point of the MHI-5
      was 70. MHI-5 <= 70 had 77 sensitivity, 72 specificity, 44 positive predicting
      value and 91% negative predicting value with the presence of depressive symptoms
      determined with BDI >= 16. CONCLUSIONS: The MHI-5 may help clinicians to screen
      for depressive symptoms in dialysis patients without using an additional
      depression screening questionnaire once the SF-36 is completed. A cut-off value
      of 70 can be used safely for the purposes of screening applications.

PMID- 22879395
TI  - Applicability of the AGREE II instrument in evaluating the development process
      and quality of current National Academy of Clinical Biochemistry guidelines.
AB  - BACKGROUND: Laboratory medicine practice guidelines (LMPGs) are an important part
      of clinical laboratory medicine. The Appraisal of Guidelines for Research and
      Evaluation II (AGREE II) instrument has been developed to evaluate the process of
      practice-guideline development and the quality of reporting. We assessed the
      applicability of AGREE II in assessing the National Academy of Clinical
      Biochemistry (NACB) LMPGs. METHODS: The NACB website was searched for all
      available LMPGs up to December 2011. Two independent appraisers used the AGREE II
      instrument to assess each LMPG identified by the search. Quality was assessed
      across 6 domains (scope and purpose, stakeholder involvement, rigor of
      development, clarity of presentation, applicability, and editorial independence),
      comprising a total of 23 items and 2 overall assessments, each scored on a 7
      point scale (1, strongly disagree, to 7, strongly agree). All scores were
      expressed as AGREE II calculated percentages (100% indicates that all items
      scored 7 by all appraisers). RESULTS: Eleven LMPGs were identified. All of the
      LMPGs provided some information seen as applicable to clinical practice by the
      appraisers. Only 5 of the LMPGs had overall scores >=50%, with a median score of
      42% (range: 8%-92%). Individual domain scores varied considerably from 0% to
      100%. One guideline achieved a very high score on the instrument. CONCLUSIONS:
      The AGREE II instrument is applicable and useful to evaluate LMPGs. All domains
      were evaluated as being useful to assess LMPGs, some were addressed well (e.g.,
      clarity of presentation), whereas others could be improved (e.g., applicability).

PMID- 22879394
TI  - Predicting outcomes after myocardial infarction by using the Chronic Kidney
      Disease Epidemiology Collaboration equation in comparison with the Modification
      of Diet in Renal Disease study equation: results from the Korea Acute Myocardial
      Infarction Registry.
AB  - BACKGROUND: The presence of chronic kidney disease is an independent prognostic
      factor in patients with myocardial infarction (MI). We compared the Chronic
      Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation and the Modification
      of Diet in Renal Disease (MDRD) study equation with regard to prognostic value in
      patients with MI. METHODS: This study analyzed a retrospective cohort of 11 050
      consecutive patients who had MI and were enrolled in the Korea Acute Myocardial
      Infarction Registry from November 2005 to August 2008. We applied the CKD-EPI
      equation and the MDRD study equation to determine the estimated glomerular
      filtration rate (eGFR) in a cohort of patients with MI. RESULTS: The mean
      eGFR(CKD-EPI) was slightly higher than that of eGFR(MDRD) (73.16 versus 72.23
      mL/min/1.73 m(2); P < 0.001). The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73
      m(2) was 26.9%, whereas that of eGFR(MDRD) was 28.5%. The area under the receiver
      operating characteristic curve was significantly larger for predicting the 1-year
      major adverse cardiovascular event (MACE) and 1-year all-cause mortality with CKD
      EPI equation (0.648 versus 0.641, 0.768 versus 0.753, respectively; P < 0.001).
      The net reclassification index for improvement in risk of 1-year MACE and 1-year
      all-cause mortality were 4.09% (P< 0.001) and 9.25% (P< 0.001), respectively.
      CONCLUSIONS: The application of the eGFR(CKD-EPI) demonstrated better predictive
      values for clinical outcomes than eGFR(MDRD) in a cohort of patients with MI.

PMID- 22879396
TI  - The effect of transparent TESTA2 on seed fatty acid biosynthesis and tolerance to
      environmental stresses during young seedling establishment in Arabidopsis.
AB  - In plants, fatty acids (FAs) and FA-derived complex lipids are major carbon and
      energy reserves in seeds. They are essential components of cellular membranes and
      cellular signal or hormone molecules. Although TRANSPARENT TESTA2 (TT2) is well
      studied for its function in regulating proanthocyanidin biosynthesis in the seed
      coat, little attention has been given to its role in affecting seed FA
      accumulation and tolerance to environmental stresses. We demonstrate that the tt2
      mutation remarkably increased the seed FA content, decreased seed weight, and
      altered the FA composition. The increase in FA content in the tt2 seeds was due
      to the relative decrease of seed coat proportion as well as the more efficient FA
      synthesis in the tt2 embryo. Microarray analysis revealed that tt2 mutation up
      regulated a group of genes critical to FA biosynthesis and embryonic development.
      The mutation also altered the gene expressions that respond to stress. The
      microarray analysis discovered that the increase in FA accumulation of the tt2
      seeds were accompanied by the significant up-regulation of FUSCA3, a
      transcriptional factor for embryonic development and FATTY ACID ELONGASE1, which
      catalyzes the elongation of FA chains. Moreover, lower seed protein accumulation
      during seed maturation also contributed to the increased seed FA accumulation in
      tt2 mutants. This study advances the understanding of the TT2 gene in seed FA
      accumulation and abiotic stresses during seed germination and seedling
      establishment.

PMID- 22879397
TI  - The role of intracellular calcium phosphate in osteoblast-mediated bone apatite
      formation.
AB  - Mineralization is a ubiquitous process in the animal kingdom and is fundamental
      to human development and health. Dysfunctional or aberrant mineralization leads
      to a variety of medical problems, and so an understanding of these processes is
      essential to their mitigation. Osteoblasts create the nano-composite structure of
      bone by secreting a collagenous extracellular matrix (ECM) on which apatite
      crystals subsequently form. However, despite their requisite function in building
      bone and decades of observations describing intracellular calcium phosphate, the
      precise role osteoblasts play in mediating bone apatite formation remains largely
      unknown. To better understand the relationship between intracellular and
      extracellular mineralization, we combined a sample-preparation method that
      simultaneously preserved mineral, ions, and ECM with nano-analytical electron
      microscopy techniques to examine osteoblasts in an in vitro model of bone
      formation. We identified calcium phosphate both within osteoblast mitochondrial
      granules and intracellular vesicles that transported material to the ECM.
      Moreover, we observed calcium-containing vesicles conjoining mitochondria, which
      also contained calcium, suggesting a storage and transport mechanism. Our
      observations further highlight the important relationship between intracellular
      calcium phosphate in osteoblasts and their role in mineralizing the ECM. These
      observations may have important implications in deciphering both how normal bone
      forms and in understanding pathological mineralization.

PMID- 22879398
TI  - Activation of the noncanonical NF-kappaB pathway by HIV controls a dendritic cell
      immunoregulatory phenotype.
AB  - HIV modulates plasmacytoid dendritic cell (pDC) activation via Toll-like receptor
      7, inducing type I IFN and inflammatory cytokines. Simultaneously, pDCs up
      regulate the expression of indoleamine 2,3 dioxygenase (IDO), which is essential
      for the induction of regulatory T cells (Tregs), which function to down-modulate
      immune activation. Here we demonstrate the crucial importance of the noncanonical
      NF-kappaB pathway in the establishment of this immunoregulatory phenotype in
      pDCs. In response to HIV, the noncanonical NF-kappaB pathway directly induces IDO
      and involves the recruitment of TNF receptor-associated factor-3 to the Toll-like
      receptor/MyD88 complex, NF-kappaB-inducing kinase-dependent IkappaB kinase-alpha
      activation, and p52/RelB nuclear translocation. We also show that pDC-induced
      Tregs can inhibit conventional DC (cDC) maturation partially through cytotoxic T
      lymphocyte antigen (CTLA)-4 engagement. Furthermore, CTLA-4 induces IDO in cDCs
      in a NF-kappaB-inducing kinase-dependent way. These CTLA-4-conditioned cDCs can
      in turn induce Treg differentiation in an IDO-dependent manner. Thus, the
      noncanonical NF-kappaB pathway is integral in controlling immunoregulatory
      phenotypes of both pDCs and cDCs.

PMID- 22879399
TI  - Comparison of early versus delayed weightbearing outcomes after microfracture for
      small to midsized osteochondral lesions of the talus.
AB  - BACKGROUND: The initiation of weightbearing is the focus of postoperative
      treatment after microfracture for osteochondral lesions of the talus. However, no
      comparative clinical study has been performed on early and delayed weightbearing
      after microfracture for osteochondral lesions of the talus. PURPOSE: The aim of
      this prospective study was to compare the clinical results of early and delayed
      weightbearing after microfracture of small to midsized osteochondral lesions of
      the talus. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2.
      METHODS: Eighty-one ankles in 81 patients with a single osteochondral lesion of
      the talus that had been treated by arthroscopic microfracture constituted the
      study cohort. Ankles were allocated to either a delayed weightbearing (DWB) group
      (41 ankles) or an early weightbearing (EWB) group (40 ankles). These 2 groups
      were comparable with regard to preoperative data. Postoperatively, patients in
      the DWB group maintained nonweightbearing for 6 weeks, but the EWB group was
      allowed early weightbearing (as tolerated) at 2 weeks. American Orthopaedic Foot
      and Ankle Society (AOFAS) ankle-hindfoot scale score, visual analog scale (VAS)
      score for pain, and ankle activity score (AAS) were used to evaluate clinical
      outcomes, and the overall mean follow-up duration was 37 months (range, 24-76
      months). RESULTS: Mean AOFAS ankle-hindfoot scores were 64.9 points in the DWB
      group and 66.5 points in the EWB group preoperatively, and these improved to 89.5
      and 89.3 at the final follow-up visits, respectively. Mean VAS scores were 7.3
      points in the DWB group and 7.4 points in the EWB group preoperatively and 1.9
      and 1.8 at final follow-up, respectively. Mean AAS in the DWB and EWB groups
      improved from 3.0 and 3.0 preoperatively to 6.0 and 6.0 at final follow-up,
      respectively. No significant differences were found between the 2 groups in terms
      of the AOFAS score, VAS score, and AAS. CONCLUSION: Two postoperative treatments
      differing by weightbearing status after arthroscopic microfracture for small to
      midsized osteochondral lesions of the talus showed good clinical results and
      similar outcomes in terms of the AOFAS score, VAS score, and AAS. The study shows
      that early weightbearing postoperative regimens can be recommended for patients
      treated by microfracture for small to midsized osteochondral lesions of the
      talus.

PMID- 22879400
TI  - Application of a clinic-based algorithm as a tool to identify female athletes at
      risk for anterior cruciate ligament injury: a prospective cohort study with a
      nested, matched case-control analysis.
AB  - BACKGROUND: When landing from a jump, the production of increased intersegmental
      knee abduction moments and coupled valgus motions has been associated with an
      increased risk of suffering a noncontact anterior cruciate ligament (ACL) injury
      in one study. This research has led to the development of a clinic-based
      algorithm that utilizes measures of knee valgus motion, knee flexion range of
      motion, body mass, tibial length, and quadriceps-to-hamstring strength ratio data
      to predict the probability of a high knee abduction moment (pKAM) when landing
      from a jump in female athletes. The ability of this algorithm to identify
      athletes at increased risk of suffering ACL injury has not been assessed.
      HYPOTHESIS: The pKAM is associated with ACL injury in female athletes. STUDY
      DESIGN: Case-control study; Level of evidence, 3. METHODS: This study was based
      on secondary analysis of data obtained from a previous investigation that focused
      on the use of the drop vertical jump (DVJ) test to assess the risk of ACL injury
      in female athletes. The DVJ screenings were performed on 1855 female high school
      and college athletes over 3 years. Knee valgus motion, knee flexion range of
      motion, and tibial length were measured from videos of the DVJ obtained during
      preseason screenings. Mass was measured using a physician's scale, and quadriceps
      to-hamstring strength ratio was included using a surrogate value. These data were
      entered into the clinic-based algorithm that determined the pKAM. The association
      of pKAM with ACL injury was assessed using conditional logistic regression.
      RESULTS: A total of 20 athletes sustained ACL injury and were matched with 45
      uninjured control athletes who were recruited from the same teams. There was no
      relationship between the risk of suffering ACL injury and pKAM, as determined by
      the clinic-based algorithm. CONCLUSION: The pKAM was not associated with
      noncontact ACL injury in our group of injured athletes and matched controls.

PMID- 22879401
TI  - Incidence of injury in Gaelic football: a 4-year prospective study.
AB  - BACKGROUND: Gaelic football is a national sport of Ireland. While predominantly
      played in Ireland, it is recognized in North America, the United Kingdom, Europe,
      and Australasia. Its high-velocity, multidirectional, and high physical contact
      elements expose players to a risk of injury. To date, prospective injury data for
      Gaelic football has been of short duration. PURPOSE: To describe the incidence
      and nature of sport-related injuries in elite male Gaelic football players over 4
      consecutive seasons. STUDY DESIGN: Descriptive epidemiology study. METHODS: Over
      the period 2007 to 2010, a total of 851 Gaelic football players were tracked.
      Players were members of county-level teams who volunteered to be included in the
      study. Team injury, training, and match play data were submitted by the team
      physiotherapist on a weekly basis through a dedicated web portal to the National
      Gaelic Athletic Association (GAA) injury database. Injury was defined using a
      time loss criterion, in accordance with consensus statements in sports applicable
      to Gaelic games. RESULTS: A total of 1014 Gaelic football injuries were recorded.
      Incidence of injury was 4.05 per 1000 hours of football training. Match-play
      injury rates were 61.86 per 1000 hours. Muscle was the most frequently injured
      tissue (42.6%) and fractures accounted for 4.4% of Gaelic football injuries.
      Lower extremity injuries predominated (76.0%). Hamstring injuries were the single
      most common injury overall, representing almost one quarter (24%) of all injuries
      and over half of muscle injuries. Anterior cruciate ligament (ACL) injuries
      accounted for 13% of knee injuries. The majority of injuries were defined as new
      injuries (74.7%), with recurrent injuries constituting 23% of all injuries. The
      majority (59%) of match play injuries occurred in the second half of the match.
      Eighty six percent of injuries caused over one week's absence from play.
      CONCLUSION: These findings illustrate injury patterns in Gaelic football using a
      prospective methodology, over 4 consecutive seasons. Comparison with published
      literature suggests that Gaelic football match play injury risk is greater than
      soccer but less than rugby union.

PMID- 22879402
TI  - Anatomic lateral ligament reconstruction in the ankle: a hybrid technique in the
      athletic population.
AB  - BACKGROUND: Anatomic and checkrein tenodesis reconstruction techniques have been
      described as a means of treatment for chronic lateral ligament instability in the
      ankle. The current article describes a hybrid procedure using the most
      advantageous concepts of both techniques for use when insufficient normal
      ligament remains to fashion a direct repair of the anterior talofibular ligament
      (ATFL). PURPOSE: The authors report the results at a minimum 1-year follow-up of
      57 patients who underwent a hybrid anatomic lateral ligament reconstruction
      technique in the ankle. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Fifty-seven patients underwent a hybrid anatomic lateral ligament reconstruction
      procedure under the care of the senior author. All patients were assessed
      preoperatively and postoperatively using the Foot and Ankle Outcome Score (FAOS)
      and Short Form-12 (SF-12) outcome score. The mean patient age at the time of
      surgery was 28 years (range, 17-65 years), including 39 male and 18 female
      patients. The mean follow-up time was 32 months (range, 12-47 months). RESULTS:
      The FAOS improved from 58 points preoperatively to 89 points postoperatively (P <
      .01). The SF-12 score improved from 48 points before surgery to 80 points at
      final follow-up (P < .01). All patients achieved mechanical stability at final
      clinical follow-up; 7 patients (12%) demonstrated functional instability.
      Functional instability was found to significantly influence not returning to
      sport at the previous level. CONCLUSION: This hybrid anatomic lateral ligament
      reconstruction technique using a peroneus longus autograft to substitute the
      native ATFL provides an alternative to anatomic reconstruction when direct repair
      is not possible.

PMID- 22879404
TI  - The other life of articles.

PMID- 22879403
TI  - No association of time from surgery with functional deficits in athletes after
      anterior cruciate ligament reconstruction: evidence for objective return-to-sport
      criteria.
AB  - BACKGROUND: Release for full activity and return to sport after anterior cruciate
      ligament reconstruction (ACLR) is often dictated by time from surgery and
      subjective opinion by the medical team. Temporal guidelines for return to sport
      may not accurately identify impaired strength and neuromuscular control, which
      are associated with increased risk for second injury (contralateral and/or
      ipsilateral limb) after ACLR in athletes. HYPOTHESES: Athletes undergoing ACLR
      and returning to sport would demonstrate functional deficits that would not be
      associated with time from surgery. STUDY DESIGN: Controlled laboratory study.
      METHODS: Thirty-three male (n = 10) and female (n = 23) athletes with unilateral
      ACLR, who were cleared by a physician to return to their sport after surgery and
      rehabilitation, performed the single-legged vertical hop test for 10 seconds on a
      portable force plate. Matched teammates of each patient were recruited to serve
      as sex-, sport-, and age-matched controls (CTRL; n = 67). Maximum vertical ground
      reaction force (VGRF) was measured during each single-limb landing. Single-limb
      symmetry index (LSI) was calculated as the ratio of the involved divided by
      uninvolved limb, expressed as a percentage. RESULTS: The single-limb vertical
      jump height LSI was reduced in the ACLR group, 89% (95% confidence interval [CI],
      83%-95%), compared with the matched CTRL group, 101% (95% CI, 96%-105%; P < .01).
      The LSI for VGRF normalized to potential energy achieved during flight of the hop
      was increased in ACLR at 112% (95% CI, 106%-117%) relative to the CTRL group at
      102% (95% CI, 98%-106%; P < .01). Linear regression analysis indicated that time
      from surgery was not associated with limb symmetry deficits in the ACLR group (P
      > .05; R (2) = .002-.01). CONCLUSION: Deficits in unilateral force development
      (vertical jump height) and absorption (normalized VGRF) persist in an athlete's
      single-limb performance after ACLR and full return to sports. These symmetry
      deficits appear to be independent of time after reconstruction. CLINICAL
      RELEVANCE: On the basis of these results, clinicians should consider assessment
      of single-limb power performance in the decision-making process for return-to
      sport release. Persistent side-to-side asymmetries may increase the risk of
      contralateral and/or ipsilateral injury.

PMID- 22879405
TI  - Suppressors, screens, and genes: an educational primer for use with "A network of
      genes antagonistic to the LIN-35 retinoblastoma protein of Caenorhabditis
      elegans".
AB  - An article by Polley and Fay in this issue of GENETICS provides an excellent
      opportunity to introduce or reinforce concepts of reverse genetics and RNA
      interference, suppressor screens, synthetic phenotypes, and phenocopy. Necessary
      background, explanations of these concepts, and a sample approach to classroom
      use of the original article, including discussion questions, are provided.

PMID- 22879406
TI  - Transvection in 2012: site-specific transgenes reveal a plethora of trans
      regulatory effects.

PMID- 22879410
TI  - Retinal thickening in HLA-B27-associated acute anterior uveitis: evolution with
      time and association with severity of inflammatory activity.
AB  - PURPOSE: To describe the evolution of retinal thickness in eyes affected with
      acute anterior uveitis (AAU) in the course of follow-up and to assess its
      correlation with severity of inflammatory activity in the anterior chamber.
      METHODS: 72 eyes (affected and fellow eyes) of 36 patients presenting with HLA
      B27-related acute anterior uveitis were included in a prospective, institutional,
      cohort study. Patients were followed daily until beginning of resolution of
      inflammatory activity and weekly thereafter. Optical coherence tomography and
      laser flare photometry were performed at each visit. Treatment consisted of
      topical corticosteroids. Main outcome measures were retinal thickness of affected
      eyes, difference in retinal thickness between affected and fellow eyes and their
      evolution in time, association between maximal retinal thickness, and initial
      laser flare photometry. RESULTS: Difference in retinal thickness between affected
      and fellow eyes became significant on average 7 days from baseline and remained
      so throughout follow-up (P < 0.001). There was a steep increase in retinal
      thickness of affected eyes, followed by a progressive decrease after reaching a
      peak value. Maximal difference in retinal thickness between affected and fellow
      eyes was observed between 17 and 25 days from baseline and exhibited a strong,
      positive correlation with initial laser flare photometry values (P = 0.015).
      CONCLUSIONS: Retinal thickness in eyes affected with AAU presents a steep
      increase over 3 to 4 weeks and then gradually decreases. Severity of inflammation
      at baseline predicts the amount of retinal thickening in affected eyes. A
      characteristic pattern of temporal response of retinal anatomy to inflammatory
      stimuli seems to arise.

PMID- 22879411
TI  - Myelin sheath decompaction, axon swelling, and functional loss during chronic
      secondary degeneration in rat optic nerve.
AB  - PURPOSE: To examine chronic changes occurring at 6 months following partial optic
      nerve (ON) transection, assessing optic axons, myelin, and visual function.
      METHODS: Dorsal ON axons were transected, leaving ventral optic axons vulnerable
      to secondary degeneration. At 3 and 6 months following partial transection,
      toluidine-blue stained sections were used to assess dimensions of the ON injury
      site. Transmission electron microscopy (TEM) images of ventral ON were used to
      quantify numbers, diameter, area, and myelin thickness of optic axons.
      Immunohistochemistry and fluoromyelin staining were used to assess
      semiquantitatively myelin protein, lipids in ventral ON, and retinal ganglion
      cells (RGCs) in midventral retina. Visuomotor function was assessed using
      optokinetic nystagmus. RESULTS: Following partial ON transection, optic axons and
      function remained disrupted at 6 months. Although ventral ON swelling observed at
      3 months (P <= 0.05) receded to normal by 6 months, ultrastructurally, myelinated
      axons remained swollen (P >= 0.05), and myelin thickness increased (P <= 0.05)
      due to loosening of lamellae and an increase in the number of intraperiodic
      lines. Axons with decompacted myelin persisted and were distinguished as having
      large axonal calibers and thicker myelin sheaths. Nevertheless, progressive loss
      of myelin lipid staining with fluoromyelin was seen at 6 months. Despite no
      further loss of ventral optic axons between 3 and 6 months (P >= 0.05),
      visuomotor function progressively declined at 6 months following partial
      transection (P <= 0.05). CONCLUSIONS: Continued decompaction of myelin, altered
      myelin structure, and swelling of myelinated axons are persistent features of the
      chronic phases of secondary degeneration and likely contribute to progressive
      loss of visual function.

PMID- 22879412
TI  - Association between shape of sclera and myopic retinochoroidal lesions in
      patients with pathologic myopia.
AB  - PURPOSE: The purpose of the study was to analyze the shape of the sclera
      determined by swept-source optical coherence tomography (OCT) and to determine
      the relationship between the shape and the myopic retinochoroidal lesions.
      METHODS: We studied 488 eyes of 272 patients with high myopia (refractive error
      >=-8.00 diopters [D] or axial length >26.5 mm) and 43 emmetropic eyes of 43
      controls (refractive error <=+/-3 D). An image of the sclera was obtained by a
      swept-source OCT prototype instrument that uses a wavelength sweeping laser
      centered on 1 MUm wavelength with an A-scan repetition rate of 100,000 Hz. The
      scans were 12 mm radial scans centered on the fovea. Seventy eyes were also
      examined by three-dimensional magnetic resonance imaging (3D MRI) to obtain the
      contour of the outer surface of the eyes. The main outcome measures, visibility
      of the entire sclera layer, scleral thickness, scleral contour, and location of
      the most protruded point of the globe, were obtained by swept-source OCT and 3D
      MRI. RESULTS: The entire thickness of the sclera was observed in 278 of 488
      (57.0%) highly myopic eyes, but the outer border was not observed in any of the
      emmetropic eyes. The mean subfoveal scleral thickness was 227.9 +/- 82.0 MUm in
      the highly myopic eyes. The sclera was thickest at 3000 MUm nasal to the fovea.
      The curvatures of the inner scleral surface of highly myopic eyes could be
      divided into curvatures that sloped toward the optic nerve, those that were
      symmetrical and centered on the fovea, those that were asymmetrical, and those
      that were irregular. Patients with irregular curvature were significantly older
      and had significantly longer axial lengths than those with other curvatures.
      Myopic fundus lesions were present significantly more frequently in the eyes with
      irregular curvature. All of the eyes whose scleral curvature sloped toward the
      optic nerve had nasally distorted shape in the 3D MRI images, and all eyes with
      temporally dislocated shape had irregular curvature. CONCLUSIONS: In vivo
      evaluations of the sclera in highly myopic eyes by swept-source OCT can provide
      important information on deformations of the sclera and how such deformities are
      related to myopic fundus lesions.

PMID- 22879407
TI  - Prions in yeast.
AB  - The concept of a prion as an infectious self-propagating protein isoform was
      initially proposed to explain certain mammalian diseases. It is now clear that
      yeast also has heritable elements transmitted via protein. Indeed, the "protein
      only" model of prion transmission was first proven using a yeast prion.
      Typically, known prions are ordered cross-beta aggregates (amyloids). Recently,
      there has been an explosion in the number of recognized prions in yeast. Yeast
      continues to lead the way in understanding cellular control of prion propagation,
      prion structure, mechanisms of de novo prion formation, specificity of prion
      transmission, and the biological roles of prions. This review summarizes what has
      been learned from yeast prions.

PMID- 22879414
TI  - Enhanced depth imaging optical coherence tomography in type 2 diabetes.
AB  - PURPOSE: To investigate the changes in macular choroidal thickness in eyes with
      various stages of diabetic retinopathy, using enhanced depth imaging optical
      coherence tomography (EDI OCT). METHODS: Sixty-three consecutive diabetic
      patients--who presented without diabetic retinopathy (NDR); with diabetic
      retinopathy (nonproliferative diabetic retinopathy [NPDR]) and no clinically
      significant macular edema (CSME-); or with NDPR and clinically significant
      macular edema (CSME+)--underwent EDI OCT. Twenty-one age- and sex-matched healthy
      subjects (21 eyes) also underwent EDI OCT. RESULTS: A total of 63 eyes of 63
      consecutive diabetic patients (26 female [41.2%]; mean age 65 +/- 9 years, range
      48-83 years) were included in the analysis. Mean best-corrected visual acuity was
      0.13 +/- 0.25 LogMAR (range 0-1). Mean CMT was 272.5 +/- 16.2 MUm in 21 NDR eyes,
      294.5 +/- 23.5 MUm in 21 NPDR/CSME- eyes, and 385.6 +/- 75.1 MUm in 21 NPDR/CSME+
      eyes. There was no difference in mean subfoveal choroidal thickness among each
      diabetic group (238.4 +/- 47.9 MUm [NDR], 207.0 +/- 55.9 MUm [NPDR/CSME-], 190.8
      +/- 48.4 MUm [NPDR/CSME+]; P = 0.23). The mean subfoveal choroidal thickness was
      significantly reduced in each diabetic group compared with the control group
      (309.8 +/- 58.5 MUm, P < 0.001). CONCLUSIONS: In diabetic eyes, there is an
      overall thinning of the choroid on EDI OCT. A decreased choroidal thickness may
      lead to tissue hypoxia and consequently increase the level of VEGF, resulting in
      the breakdown of the blood-retinal barrier and development of macular edema.

PMID- 22879413
TI  - Fibrinogen, riboflavin, and UVA to immobilize a corneal flap--molecular
      mechanisms.
AB  - PURPOSE: Tissue glue containing fibrinogen (FIB) and riboflavin (RF), upon
      exposure to long wavelength ultraviolet light (UVA, 365 nM) has been proposed
      potentially to solve long-standing problems presented by corneal wound and
      epithelial ingrowth side-effects from laser-assisted in situ keratomileuis
      (LASIK). Data presented in a previous study demonstrated an ability of FIB + RF +
      UVA to adhere two stromal surfaces; however, to our knowledge no molecular
      mechanisms have been proposed to account for interactions occurring between
      corneal extracellular matrix (ECM) and tissue glue molecules. Here, we document
      several covalent and noncovalent interactions between these classes of
      macromolecules. METHODS: SDS-PAGE and Western blot techniques were used to
      identify covalent interactions between tissue glue molecules and corneal ECM
      molecules in either the presence or absence of RF and UVA, in vitro and ex vivo.
      Surface plasmon resonance (SPR) was used to characterize noncovalent
      interactions, and obtain k(a), k(d), and K(D) binding affinity values. RESULTS:
      SDS-PAGE and Western blot analyses indicated that covalent interactions occurred
      between neighboring FIB molecules, as well as between FIB and collagen type I
      (Coll-I) proteins (in vitro and ex vivo). These interactions occurred only in the
      presence of RF and UVA. SPR data demonstrated the ability of FIB to bind
      noncovalently to corneal stroma molecules, Coll-I, decorin, dermatan sulfate, and
      corneal basement membrane molecules, laminin and heparan sulfate--only in the
      presence of Zn(2+). CONCLUSIONS: Covalent and (zinc-mediated) noncovalent
      mechanisms involving FIB and stromal ECM molecules contribute to the adhesion
      created by FIB + RF + UVA.

PMID- 22879415
TI  - Tracking retinal microgliosis in models of retinal ganglion cell damage.
AB  - PURPOSE: To investigate the longitudinal profiles of microgliosis after optic
      nerve injury induced by optic nerve crush and acute elevation of intraocular
      pressure (IOP). METHODS: A confocal scanning laser ophthalmoscope was used to
      image the retinal microglia of the CX3CR1(GFP/+) transgenic mice in vivo at
      baseline, 3 days and then weekly for 4 weeks after optic nerve crush (n = 3), and
      after elevating the IOP to 110 mm Hg for 30 (n = 3) or 60 (n = 3) minutes.
      RESULTS: After optic nerve crush, the density of microglia increased by 2.43 +/-
      0.19-fold at week 1 and then gradually declined with 2.04 +/- 0.24-, 1.69 +/-
      0.25-, and 1.29 +/- 0.11-fold increases at week 2, 3, and 4, respectively.
      Microgliosis followed a similar pattern after acute IOP elevation and the
      increase in microglia was associated with the duration of IOP elevation. There
      were 1.35 +/- 0.17- and 2.03 +/- 0.08-fold increases in microglia at week 1, and
      1.15 +/- 0.11- and 1.11 +/- 0.10-fold increases at week 4, after 30 and 60
      minutes of acute IOP elevation, respectively. The morphology of microglia changed
      from ramified to ameboid form in 1 week, and then returned to ramified form in
      the subsequent weeks. There was a significant negative association between the
      number of surviving retinal ganglion cells (RGCs) and the extent of microgliosis
      during the follow-up period (R2 = 0.72, P = 0.004). CONCLUSIONS: Longitudinal in
      vivo imaging of the retinal microglia can provide an effective approach to study
      microgliosis and its association with RGC degeneration.

PMID- 22879408
TI  - Everything you ever wanted to know about Saccharomyces cerevisiae telomeres:
      beginning to end.
AB  - The mechanisms that maintain the stability of chromosome ends have broad impact
      on genome integrity in all eukaryotes. Budding yeast is a premier organism for
      telomere studies. Many fundamental concepts of telomere and telomerase function
      were first established in yeast and then extended to other organisms. We present
      a comprehensive review of yeast telomere biology that covers capping,
      replication, recombination, and transcription. We think of it as yeast telomeres-
      soup to nuts.

PMID- 22879416
TI  - Bidirectional, optical sign-dependent regulation of BMP2 gene expression in chick
      retinal pigment epithelium.
AB  - PURPOSE: We explored the role of bone morphogenic protein 2 (BMP2) in defocus
      induced ocular growth using gene expression changes in RPE as a surrogate.
      METHODS: Young White-Leghorn chickens were used in this study. Normal gene
      expression of BMP2 and its receptors was examined in retina, RPE, and choroid,
      and BMP2 protein expression assessed in the same tissues using Western blots and
      immunohistochemistry. Quantitative PCR (qPCR) was used to assess the effects of
      short-term exposure (2 or 48 hours) to monocular +10 and -10 diopter (D) lenses,
      on RPE gene expression of BMP2 and its receptors. Ocular growth was assessed
      using A-scan ultrasonography. RESULTS: In the eyes of untreated chickens, BMP2
      mRNA was expressed more highly in RPE compared to retina and choroid and all
      three tissues expressed BMP2 protein. The gene expression for all three receptors
      also was detected in these tissues, with BMPR2 showing highest and BMPR1B lowest
      expression. BMP2 was up-regulated in the RPE from eyes wearing +10 D lenses,
      which exhibited shorter than normal vitreous chambers (VCDs) and thickened
      choroids, while BMP2 was down-regulated in the RPE from eyes wearing -10 D
      lenses, which developed enlarged VCDs. These treatments did not induce
      differential expression of BMP receptors in RPE. CONCLUSIONS: That mRNA
      expression of BMP2 in chick RPE shows bidirectional, defocus sign-dependent
      changes is suggestive of a role for BMP2 in eye growth regulation, although the
      diffuse ocular expression of BMP2 and its receptors suggests complex growth
      modulatory signal pathways.

PMID- 22879417
TI  - Seven-year changes in corneal power and aberrations after PRK or LASIK.
AB  - PURPOSE: To examine long-term changes in corneal power and aberrations in myopic
      patients randomized to photorefractive keratectomy (PRK) or laser in situ
      keratomileusis (LASIK). METHODS: Forty-five patients with myopia from -6 to -8
      diopters (spherical equivalent refraction) were randomized to PRK (n = 20) or
      LASIK (n = 25). Patients were examined preoperatively and for up to 7 years after
      surgery. Measurements included refraction, topography (TMS-1), and ultrasound
      pachymetry. By 3 years, 16 PRK and 15 LASIK patients were examined and by 7
      years, 9 PRK and 7 LASIK subjects were available. Only patients who had not been
      reoperated and attended the two late controls were included in data analyses.
      Optical analysis of topographic data was used to calculate corneal power and
      wavefront aberrations. RESULTS: PRK and LASIK caused a similar reduction in
      corneal power. During the first year after PRK, corneal power increased, but
      remained stable from 1 to 7 years. In contrast, corneal power continued to
      increase from 1 to 7 years after LASIK. Both PRK and LASIK caused an increase in
      coma-like and spherical aberrations that remained constant for 7 years. No
      significant changes in other higher-order aberrations were observed. CONCLUSIONS:
      The cornea may not be stable even 7 years after LASIK, as indicated by the
      continuing increase in corneal power. In contrast, PRK appears stable from 1 year
      post surgery. Coma-like and spherical aberrations are permanently increased after
      PRK and LASIK. (ClinicalTrials.gov number, NCT00404105.).

PMID- 22879418
TI  - The relationship between variability and sensitivity in large-scale longitudinal
      visual field data.
AB  - PURPOSE: Evaluation of progressive visual field (VF) damage is often based on
      pointwise sensitivity data from standard automated perimetry; however, frequency
      of seeing and test-retest studies demonstrate that these measurements can be
      highly variable, especially in areas of damage. The aim of this study was to
      characterize VF variability by the level of sensitivity using a statistical
      method to quantify heteroscedasticity. METHODS: A total of 14,887 Humphrey 24-2
      SITA Standard VFs from 2736 patients (2736 eyes) attending Moorfields Eye
      Hospital from 1997 to 2009 were studied retrospectively. The VF series of each
      eye was analyzed using pointwise linear regression of sensitivity over time, with
      residuals (difference from fitted-value) from each regression pooled according to
      both observed and fitted sensitivities. RESULTS: The median (interquartile range)
      patient age, follow-up, and series length was 64 (54-71) years, 5.5 (3.9-7.0)
      years, and 6 (5-7) VFs, respectively. The inferred variability as a function of
      fitted-sensitivity was in good agreement with previous estimates. Variability was
      also described as a function of measured sensitivity, which confirmed that
      variability increased rapidly as the observed sensitivity decreased. CONCLUSIONS:
      This study highlights a new approach for characterizing VF variability by the
      level of sensitivity. A considerable strength of the method is that inference is
      based on thousands of clinic patients rather than the tens of subjects in test
      retest studies. The results can help distinguish real VF progression from
      measurement variability and will be used in models for glaucoma progression
      detection.

PMID- 22879419
TI  - Pretreatment with proteasome inhibitors protects against oxidative injuries via
      PPARalpha-dependent and -independent pathways in ARPE-19 cells.
AB  - PURPOSES: Oxidative processes may play important roles in age-related macular
      degeneration. Previous studies have suggested that enhancing proteasome activity
      by pretreatment with low doses of proteasome inhibitors reduces injury from
      oxidative damage in neuronal cultures. The objective of the current study was to
      determine whether proteasome inhibitors could ameliorate the toxicity from
      oxidative stresses in ARPE-19 cells and to dissect the pathways that may mediate
      these protective effects. METHODS: The toxicity of oxidative stressors menadione
      (VK3) and 4-hydroxynonenal (4-HNE) and the protective effects of proteasome
      inhibitors, including MG-132 and clasto-lactacystin-beta-lactone (LA), were
      studied in ARPE-19 cells. Binding and activation of the peroxisome proliferator
      activated receptors (PPARs) family of transcription factors were studied using
      electrophoretic mobility shift assay (EMSA) and a peroxisome proliferator
      activated response element (PPRE)-driven dual-luciferase reporter gene. RESULTS:
      An 18-hour pretreatment with 30 to 300 nM MG-132 or 300 to 1000 nM LA reduced the
      toxicity of menadione or 4-HNE in ARPE-19 cells. The protective effects of MG-132
      pretreatment were partially reversed by the PPARalpha antagonist GW6471 but not
      by the PPARgamma antagonist GW9662; in contrast, neither agent reduced the
      protective effects of LA. MG-132 but not LA induced increased expression of a
      PPRE-driven luciferase reporter gene in a dose-dependent manner. Nuclear proteins
      isolated from ARPE-19 cells treated by MG-132 had increased binding to PPRE
      sequences as measured by EMSA. CONCLUSIONS: Our data suggest that pretreatment
      with proteasome inhibitors reduces oxidative injury in ARPE-19 cells and that the
      underlying mechanisms are different for different proteasome inhibitors, with
      PPARalpha-dependent effects for MG-132 and PPAR-independent effects for LA.

PMID- 22879420
TI  - Image jitter enhances visual performance when spatial resolution is impaired.
AB  - PURPOSE: Visibility of low-spatial frequency stimuli improves when their contrast
      is modulated at 5 to 10 Hz compared with stationary stimuli. Therefore, temporal
      modulations of visual objects could enhance the performance of low vision
      patients who primarily perceive images of low-spatial frequency content. We
      investigated the effect of retinal-image jitter on word recognition speed and
      facial emotion recognition in subjects with central visual impairment. METHODS:
      Word recognition speed and accuracy of facial emotion discrimination were
      measured in volunteers with AMD under stationary and jittering conditions.
      Computer-driven and optoelectronic approaches were used to induce retinal-image
      jitter with duration of 100 or 166 ms and amplitude within the range of 0.5 to
      2.6 degrees  visual angle. Word recognition speed was also measured for
      participants with simulated (Bangerter filters) visual impairment. RESULTS: Text
      jittering markedly enhanced word recognition speed for people with severe visual
      loss (101 +/- 25%), while for those with moderate visual impairment, this effect
      was weaker (19 +/- 9%). The ability of low vision patients to discriminate the
      facial emotions of jittering images improved by a factor of 2. A prototype of
      optoelectronic jitter goggles produced similar improvement in facial emotion
      discrimination. Word recognition speed in participants with simulated visual
      impairment was enhanced for interjitter intervals over 100 ms and reduced for
      shorter intervals. CONCLUSIONS: Results suggest that retinal-image jitter with
      optimal frequency and amplitude is an effective strategy for enhancing visual
      information processing in the absence of spatial detail. These findings will
      enable the development of novel tools to improve the quality of life of low
      vision patients.

PMID- 22879421
TI  - Characterization of vitreoretinal interface disorders using OCT in the
      interventional phase 3 trials of ocriplasmin.
AB  - PURPOSE: We determined the reproducibility of a novel optical coherence
      tomography (OCT) protocol designed to evaluate formally vitreoretinal interface
      abnormalities on scans obtained during two phase 3 studies of intravitreal
      ocriplasmin to treat symptomatic vitreomacular adhesion with or without macular
      hole. METHODS: Certified technicians obtained time-domain OCT scans that included
      a macular thickness map (MTM), Fast MTM, and three high resolution linear scans:
      one 10 mm horizontal and one 10 mm vertical through the optic nerve head (ONH),
      and one 10 mm 5-degree-offset through the ONH and fovea. Reading Center teams
      graded all 3695 scans from 652 study eyes for pre-established quantitative and
      morphologic features. Grading reproducibility at baseline and follow-up visits
      was tested for presence of vitreomacular adhesion (VMA), width of vitreous
      adhesion (focal <1500 MUm versus broad >1500 MUm), presence and minimum width of
      full thickness macular hole (FTMH), and presence of epiretinal membrane (ERM).
      RESULTS: Team grading reproducibility for VMA (kappa 0.91, 95% confidence
      interval [CI] 0.81-1.00), broad versus focal width of vitreous adhesion (kappa
      0.87, 95% CI 0.78-0.95), FTMH (kappa 0.87, 95% CI 0.78-0.95), and ERM (kappa
      0.87, 95% CI 0.78-0.95) was high. Percent agreement was 97%, 92%, 95%, and 82%
      for VMA, vitreous adhesion width, FTMH, and ERM, respectively. For repeated
      measurements of FTMH width, the intraclass correlation was 0.89 (95% CI 0.85
      0.93), and the mean paired difference between grading team measurements was 34.4
      MUm (95% limits of agreement -149.5-218.2 MUm). CONCLUSIONS: Quantitative and
      morphologic vitreoretinal interface features were assessed reproducibly using a
      newly developed OCT scan acquisition and grading protocol. This protocol will be
      useful to evaluate OCT endpoints in future clinical trials, and can facilitate
      identification of vitreoretinal interface pathology during care of individual
      patients. (ClinicalTrials.gov number, NCT00781859 and NCT00798317.).

PMID- 22879422
TI  - Auditory and visual temporal processing disruption in open angle glaucoma.
AB  - PURPOSE: Open angle glaucoma (OAG) is increasingly being viewed as an age-related
      neurodegenerative condition that may occur in individuals who are innately
      susceptible to global (autonomic) neural injury. Recent data support the
      plausibility of auditory neural impairment in a proportion of individuals with
      OAG, with results showing a key disruption to processing temporal properties of
      sound. This study tested the hypothesis that temporal processing deficits
      consistent with central (cortical) processing abnormalities are present in both
      the visual and auditory domains in individuals with glaucoma. METHODS: A series
      of tasks designed to test progressively more complex aspects of temporal
      processing were conducted in 25 OAG individuals and 25 age- and sex-matched
      controls. For audition, baseline measurement of hearing sensitivity was followed
      by functional assessment of amplitude modulation detection, frequency
      discrimination at two reference levels, and speech perception. For vision,
      measures of foveal temporal contrast detection at two flicker rates, speed
      discrimination at two reference velocities, and coherent global motion detection
      were assessed. RESULTS: A significant proportion of the OAG cohort displayed an
      impairment in auditory low-frequency discrimination, speech perception, visual
      speed discrimination for slow velocities and/or visual global motion detection,
      compared to controls (36%, 25%, 39%, and 34% respectively, were outside the 90th
      percentile of control performance; P < 0.05). CONCLUSIONS: A subgroup of
      individuals with OAG displayed impaired auditory temporal processing concurrent
      with signs of visual temporal processing impairment. These temporal processing
      deficits were in the presence of normal sound detection and normal central
      luminance increment thresholds.

PMID- 22879424
TI  - Impact of glaucoma on visual functioning in Indians.
AB  - PURPOSE: To evaluate the impact of glaucoma on visual functioning in Indians.
      METHODS: Patients attending the glaucoma service who had undergone a
      comprehensive glaucoma evaluation were recruited. Better mean deviation (MD,
      using Humphrey Field Analyzer program 24-2) between two eyes was used to classify
      participants into mild, moderate, and severe visual field (VF) loss groups.
      Participants were administered the Glaucoma Quality of Life-15 (GQL-15)
      questionnaire. Rasch analysis was used to validate the GQL-15 and its four
      subscales. Linear regression was used to determine associations between GQL-15
      scores and VF loss after adjusting for sociodemographic variables. RESULTS: A
      total of 198 patients (mean age +/- SD, 59.8 +/- 12.3 years; 67% male) were
      recruited. Participants with severe VF loss (39%) followed by mild loss (35%)
      comprised the largest group. Rasch analysis resulted in a 10-item reliable and
      valid questionnaire: the Glaucoma Activity Limitation-10 (GAL-10). Although a
      single subscale, "peripheral vision," met requirements of the Rasch model, it
      could not be preserved in the GAL-10. In multivariate analyses, the middle-income
      group (compared with higher income) and severe VF-loss (compared with mild VF
      loss) participants reported significantly poorer functioning on GAL-10 ([beta =
      0.84; 95% confidence interval (CI), 0.16-1.52; P = 0.02] and [beta = 1.19; 95%
      CI, 0.61-1.78; P < 0.000], respectively). None of these associations were,
      however, clinically significant. CONCLUSIONS: Glaucoma patients in India,
      especially those with severe VF loss, face significant challenges in performing
      daily tasks and in mobility. It is important to prevent progression such that
      activity limitation is minimized in glaucoma patients.

PMID- 22879423
TI  - Macular pigment imaging in AREDS2 participants: an ancillary study of AREDS2
      subjects enrolled at the Moran Eye Center.
AB  - PURPOSE: Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo
      controlled study designed to determine whether supplementation with 10 mg of
      lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age
      related macular degeneration (AMD). Although some biomarkers of response to
      carotenoid supplementation such as serum concentrations are part of the AREDS2
      protocol, measurement of carotenoid concentrations in the eye and other tissues
      is not. In this approved ancillary study, macular pigment optical density (MPOD),
      macular pigment distributions, and skin carotenoid levels at enrollment and at
      each annual visit were measured to assess baseline carotenoid status and to
      monitor response to assigned interventions. METHODS: All subjects enrolled at the
      Moran Eye Center had MPOD and macular pigment spatial distributions measured by
      dual-wavelength autofluorescence imaging and total skin carotenoids measured by
      resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was
      unusually high relative to an age-matched control group that did not consume
      carotenoid supplements regularly, consistent with the high rate of habitual
      lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment.
      MPOD did not correlate with serum or skin carotenoid measurements. CONCLUSIONS:
      Useful information is provided through this ancillary study on the ocular
      carotenoid status of AREDS2 participants in the target tissue of lutein and
      zeaxanthin supplementation: The macula. When treatment assignments are unmasked
      at the conclusion of the study, unique tissue-based insights will be provided on
      the progression of AMD in response to long-term, high-dose carotenoid
      supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.).

PMID- 22879425
TI  - Reproducibility of activation maps for longitudinal studies of visual function by
      functional magnetic resonance imaging.
AB  - PURPOSE: To test the intra- and intersubject reproducibility of brain activation
      patterns that underlie visually guided saccades and word recognition in normally
      sighted subjects and patients with macular degeneration using functional magnetic
      resonance imaging (fMRI). METHODS: Ten normally sighted subjects and five
      patients with macular degeneration were asked to perform two visually guided
      saccade tasks and two word-recognition tasks during fMRI with behavioral
      monitoring. The fMRI measurements were repeated three times at intervals of at
      least 4 weeks between sessions. The intrasubject reproducibility of the brain
      activation patterns was examined in a model-independent manner by comparing the
      distributions of activation across the frontal, parietal, temporal, and occipital
      brain lobes using Intraclass Correlation Coefficients (ICCs). Intersubject
      reproducibility was examined by repeated-measure ANOVA. Results. Control subjects
      showed overall higher intrasubject reproducibility of brain activation patterns
      (75% ICCs > 0.5) than that of patients with macular degeneration (56% ICCs >
      0.5). The intrasubject reproducibility for the patients improved when the target
      location was fixed, as in the word-recognition tasks (75% ICCs > 0.5), compared
      with the visually saccade tasks (37% ICCs > 0.5). Intersubject variability of
      brain activation patterns was strikingly high for both the control and patient
      groups. CONCLUSIONS: The fMRI method can serve as a reliable within-subjects
      measure of brain activation that has potential for measuring longitudinal changes
      in brain networks associated with rehabilitation training. Striking intersubject
      variability reflected at the level of lobes of the brain among control subjects
      with similar behavioral performance, suggests individual analysis is necessary
      when implementing longitudinal brain activation studies.

PMID- 22879426
TI  - A population study of childhood maltreatment and asthma diagnosis: differential
      associations between child protection database versus retrospective self-reported
      data.
AB  - OBJECTIVE: Despite growing evidence from longitudinal studies of a link between
      early-life stress and the development of asthma, very few of these examine one of
      the most severe types of early-life stress: childhood maltreatment. Cross
      sectional studies on this topic have relied on retrospective self-reports of
      maltreatment. This study investigates associations between childhood maltreatment
      indicated by child protection agency records versus self-reports and lifetime
      asthma diagnosis in young adults, adjusting for socioeconomic status and mental
      disorders. METHODS: A nationally representative general population survey of DSM
      IV mental disorders in New Zealand (n = 12,992) obtained information on lifetime
      diagnoses of chronic physical conditions. Information from a subsample of survey
      respondents aged 16 to 27 years (n = 1413) was linked with a national child
      protection database to identify respondents with a history of agency involvement,
      which was used as a proxy for childhood maltreatment. Retrospective reports of
      maltreatment were also obtained. RESULTS: Child protection agency history was
      associated with elevated odds (odds ratio = 2.88 [95% confidence interval = 1.7
      4.74]) of a lifetime diagnosis of asthma. After adjusting for a variety of
      indicators of socioeconomic status, lifetime mental disorders, lifetime smoking,
      and body mass index, this association remained significantly elevated (odds ratio
      = 2.26 [95% confidence interval = 1.33-3.83]). Retrospectively self-reported
      maltreatment in childhood was not associated with asthma. CONCLUSIONS: Childhood
      maltreatment was associated with elevated odds of asthma diagnosis. These
      findings are consistent with the possibility that early-life stress may be one of
      the environmental factors that increase the risk of asthma in genetically
      vulnerable individuals.

PMID- 22879427
TI  - The bidirectional association between depression and insomnia: the HUNT study.
AB  - OBJECTIVE: Depression and insomnia are closely linked, yet our understanding of
      their prospective relationships remains limited. The aim of the current study was
      to investigate the directionality of association between depression and insomnia.
      METHODS: Data were collected from a prospective population-based study comprising
      the most recent waves of the Nord-Trondelag Health Study (HUNT) (the HUNT2 in
      1995-1997 and the HUNT3 in 2006-2008). A total of 24,715 persons provided valid
      responses on the relevant questionnaires from both surveys. Study outcomes were
      onset of depression or insomnia at HUNT3 in persons not reporting the other
      disorder in HUNT2. RESULTS: Both insomnia and depression significantly predicted
      the onset of the other disorder. Participants who did not have depression in
      HUNT2 but who had insomnia in both HUNT2 and HUNT3 had an odds ratio (OR) of 6.2
      of developing depression at HUNT3. Participants who did not have insomnia in
      HUNT2 but who had depression in both HUNT2 and HUNT3 had an OR of 6.7 of
      developing insomnia at HUNT3. ORs were only slightly attenuated when adjusting
      for potential confounding factors. CONCLUSIONS: The results support a
      bidirectional relationship between insomnia and depression. This finding stands
      in contrast to the previous studies, which have mainly focused on insomnia as a
      risk factor for the onset of depression.

PMID- 22879428
TI  - Increased body mass index is associated with a global and distributed decrease in
      white matter microstructural integrity.
AB  - OBJECTIVE: Obesity and decreased physical health are linked to deficits in
      several cognitive domains. The broad range of cognitive problems linked to
      obesity suggests a global mechanism that may interfere with multiple neural
      systems. We examined how variation in body mass index (BMI) is associated with
      the microstructural integrity of fiber connections in the human brain. METHODS:
      White matter structure was measured using diffusion tensor imaging in 28
      participants (mean age = 30 years) with BMI scores ranging from normal weight to
      obese (19.5-45.7 kg/m(2)) based on standard BMI criteria. RESULTS: Using a whole
      brain voxelwise analysis, we found that, across participants, the fractional
      anisotropy of white matter voxels parametrically decreased with increasing BMI
      (63% of white matter voxels). Midbrain and brainstem tracts were among the
      pathways most strongly associated with obesity (r = -0.18 to -0.33, df = 27, all
      p values < .05). We also observed a weaker overall diffusion signal in
      individuals with higher BMI than controls with normal weight (r = -0.14 to -0.71,
      df = 27, for 67% of fiber pathways tested, all p values < .05). After controlling
      for this decrease in general diffusivity, we found that decreases in fractional
      anisotropy stemmed from both a decrease in axial diffusivity (p < .05) and an
      increase in radial diffusivity (p < .05). CONCLUSIONS: Our results show that
      increased BMI is globally associated with a reduction in white matter integrity
      throughout the brain, elucidating a potential mechanism by which changes in
      physical health may influence cognitive health.

PMID- 22879429
TI  - Maternal early-pregnancy vitamin D status is associated with maternal depressive
      symptoms in the Amsterdam Born Children and Their Development cohort.
AB  - OBJECTIVE: To examine low maternal vitamin D status as a potential risk factor
      for high levels of depressive symptoms in a pregnant population. METHODS: In the
      Amsterdam Born Children and Their Development cohort, maternal serum vitamin D (n
      = 4236) was measured during early pregnancy (median, 13 weeks) and labeled
      "deficient" (<= 29.9 nM), "insufficient" (30-49.9 nM), "sufficient" (50-79.9 nM),
      and "normal" (>= 80 nM). Maternal depressive symptoms were measured by the Center
      for Epidemiological Studies Depression Scale at 16-week gestation. The
      association of vitamin D status with high levels of depressive symptoms (Center
      for Epidemiological Studies Depression score >= 16) was assessed by multivariate
      logistic regression (final sample, 4101). RESULTS: Overall, 23% of women had
      vitamin D deficiency, and 21% of women had vitamin D insufficiency. Women with
      high levels of depressive symptoms (28%) had lower vitamin D concentrations than
      women with low levels of depressive symptoms (p < .001). After adjustment for
      constitutional factors, life-style and psychosocial covariates, and
      sociodemographic factors, vitamin D deficiency (odds ratio [OR], 1.48; 95%
      confidence interval [CI], 1.13-1.95) and insufficiency (OR, 1.44; 95% CI, 1.12
      1.85) were significantly associated with high levels of depressive symptoms.
      Additional analyses revealed a linear trend, with an OR of 1.05 (95% CI, 1.02
      1.08) for each 10-nM decrease in vitamin D status. CONCLUSIONS: In this study,
      low early-pregnancy vitamin D status was associated with elevated depressive
      symptoms in pregnancy. Further research, using a randomized controlled design,
      would be required to confirm the causality of this association and the potential
      benefits of higher vitamin D intake for psychosocial health.

PMID- 22879430
TI  - Copy-number-aware differential analysis of quantitative DNA sequencing data.
AB  - Developments in microarray and high-throughput sequencing (HTS) technologies have
      resulted in a rapid expansion of research into epigenomic changes that occur in
      normal development and in the progression of disease, such as cancer. Not
      surprisingly, copy number variation (CNV) has a direct effect on HTS read
      densities and can therefore bias differential detection results. We have
      developed a flexible approach called ABCD-DNA (affinity-based copy-number-aware
      differential quantitative DNA sequencing analyses) that integrates CNV and other
      systematic factors directly into the differential enrichment engine.

PMID- 22879431
TI  - Genome-wide search for novel human uORFs and N-terminal protein extensions using
      ribosomal footprinting.
AB  - So far, the annotation of translation initiation sites (TISs) has been based
      mostly upon bioinformatics rather than experimental evidence. We adapted
      ribosomal footprinting to puromycin-treated cells to generate a transcriptome
      wide map of TISs in a human monocytic cell line. A neural network was trained on
      the ribosomal footprints observed at previously annotated AUG translation
      initiation codons (TICs), and used for the ab initio prediction of TISs in 5062
      transcripts with sufficient sequence coverage. Functional interpretation
      suggested 2994 novel upstream open reading frames (uORFs) in the 5' UTR, 1406
      uORFs overlapping with the coding sequence, and 546 N-terminal protein
      extensions. The TIS detection method was validated on the basis of previously
      published alternative TISs and uORFs. Among primates, TICs in newly annotated
      TISs were significantly more conserved than control codons, both for AUGs and
      near-cognate codons. The transcriptome-wide map of novel candidate TISs derived
      as part of the study will shed further light on the way in which human proteome
      diversity is influenced by alternative translation initiation and regulation.

PMID- 22879432
TI  - Obstetric nephrology: renal hemodynamic and metabolic physiology in normal
      pregnancy.
AB  - Glomerular hyperfiltration, altered tubular function, and shifts in electrolyte
      fluid balance are among the hallmark renal physiologic changes that characterize
      a healthy pregnancy. These adjustments are not only critical to maternal and
      fetal well being, but also provide the clinical context for identifying
      gestational aberrations in renal function and electrolyte composition. Systemic
      vasodilation characterizes early gestation and produces increments in renal
      plasma flow and GFR, the latter of which is maintained into the postpartum
      period. In addition, renal tubular changes allow for the accumulation of
      nutrients and electrolytes necessary for fetal growth such that wasting of
      proteins, glucose, and amino acids in urine is limited in pregnancy and total
      body stores of electrolytes increase throughout gestation. Substantial insight
      into the mechanisms underlying these complex adjustments can be gleaned from the
      available animal and human literature, but our understanding in many areas
      remains incomplete. This article reviews the available literature on renal
      adaptation to normal pregnancy, including renal function, tubular function, and
      electrolyte-fluid balance, along with the clinical ramifications of these
      adjustments, the limitations of the existing literature, and suggestions for
      future studies.

PMID- 22879434
TI  - Onco-nephrology: tumor lysis syndrome.
AB  - Tumor lysis syndrome (TLS) describes the clinical and laboratory sequelae that
      result from the rapid release of intracellular contents of dying cancer cells. It
      is characterized by the release of potassium, phosphorous, and nucleic acids from
      cancer cells into the blood stream, with the potential to cause hyperkalemia;
      hyperphosphatemia and secondary hypocalcemia; hyperuricemia; AKI; and, should
      usual homeostatic mechanisms fail, death. TLS most commonly follows treatment of
      hematologic malignancies, such as acute lymphocytic or lymphoblastic leukemia,
      acute myeloid leukemia, and Burkitt lymphoma, but also occurs after treatment of
      other bulky or rapidly growing tumors, particularly if the patient is highly
      sensitive to the effects of cytotoxic chemotherapy. Prevention and treatment
      depend on prompt recognition of patients at risk, volume repletion, allopurinol,
      rasburicase (a novel recombinant urate oxidase), and, when indicated, dialysis.

PMID- 22879433
TI  - Onco-nephrology: AKI in the cancer patient.
AB  - AKI is common in patients with cancer, and it causes interruptions in therapy and
      increased hospital length of stay, cost, and mortality. Although cancer patients
      are susceptible to all of the usual causes of AKI in patients without cancer,
      there are a number of AKI syndromes that occur more frequently or are unique to
      this patient population. AKI also confers substantially increased risk of short
      term death, and the ability to reverse AKI portends a better outcome in some
      cancers, such as multiple myeloma. Several trends in oncology, including
      increased survival, better supportive care, older patients who have received
      multiple chemotherapy regimens, and new therapeutic options, are driving an
      increase in the numbers of cancer patients who develop AKI. As a result,
      nephrologists should be increasingly familiar with the diagnosis, management, and
      treatment of AKI in this setting. Here, we summarize recent data on epidemiology
      of AKI in cancer patients, describe the most common AKI syndromes in this
      population, and highlight emerging areas in the growing field of onconephrology.

PMID- 22879435
TI  - Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy.
AB  - AKI in pregnancy remains a cause of significant fetomaternal mortality and
      morbidity, particularly in developing countries. Hypertensive complications of
      pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low
      platelets count syndrome) are the leading cause of AKI in pregnancy worldwide.
      Thrombotic microangiopathy is another peculiar and devastating cause of AKI in
      pregnancy. During the last decade, our understanding, and in some cases, our
      management, of these causes of AKI in pregnancy has dramatically improved. For
      instance, convincing data have linked pre-eclampsia/eclampsia to an increase in
      circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce
      endothelial cell dysfunction, hypertension, and proteinuria. Several distinct
      pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic
      microangiopathy occurring during pregnancy, have been established. Thrombotic
      microangiopathy, which can present as hemolytic uremic syndrome or thrombotic
      thrombocytopenic purpura, can be reclassified in four potentially overlapping
      subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif,
      member 13 deficiency-related thrombotic microangiopathy, complement alternative
      pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic
      microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic
      microangiopathy of undetermined mechanism. In most cases, pregnancy is only a
      precipitating factor for thrombotic microangiopathy. Treatment of thrombotic
      microangiopathy occurring during pregnancy should be tailored to the underlying
      pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with
      a thrombospondin type 1 motif, member 13 serum activity in the setting of
      thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B
      cell-depleting therapy and (2) inhibition of complement alternative pathway
      activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody
      (eculizumab).

PMID- 22879436
TI  - CKD, plasma lipids, and common carotid intima-media thickness: results from the
      multi-ethnic study of atherosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Altered levels of atherogenic lipoproteins have been
      shown to be common in mild kidney dysfunction. This study sought to determine the
      associations between plasma lipids (including LDL particle distribution) and
      subclinical atherosclerosis measured by the common carotid intima-media thickness
      (IMT) across levels of estimated GFR (eGFR) and to assess whether inflammation
      modifies these associations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross
      sectional analyses of 6572 participants in the Multi-Ethnic Study of
      Atherosclerosis enrolled from 2000 to 2002 were performed. RESULTS: CKD, defined
      as eGFR <60 ml/min per 1.73 m(2), was present in 853 individuals (13.0%).
      Associations of total cholesterol and LDL cholesterol (LDL-C) with IMT were J
      shaped, particularly among participants with CKD (P value for interaction,
      P=0.01). HDL cholesterol (HDL-C) and small-dense LDL-C were consistently and
      linearly associated with IMT across levels of eGFR. The results showed
      differences in IMT of -21.41 (95% confidence interval, -41.00, -1.57) in eGFR
      >=60 and -58.49 (-126.61, 9.63) in eGFR <60 per unit difference in log
      transformed HDL-C, and 4.83 (3.16, 6.50) in eGFR >=60 and 7.48 (1.45, 13.50) in
      eGFR <60 per 100 nmol/L difference in small-dense LDL. Among participants with
      CKD, inflammation significantly modified the associations of total cholesterol
      and LDL-C with IMT (P values for interaction, P<0.01 and P<0.001, respectively).
      CONCLUSIONS: Compared with total cholesterol and LDL-C, abnormalities in HDL-C
      and small-dense LDL-C are more strongly and consistently associated with
      subclinical atherosclerosis in CKD. Inflammation modifies the association between
      total cholesterol and LDL-C with IMT.

PMID- 22879437
TI  - Obstetric nephrology: lupus and lupus nephritis in pregnancy.
AB  - SLE is a multi-organ autoimmune disease that affects women of childbearing age.
      Renal involvement in the form of either active lupus nephritis (LN) at the time
      of conception, or a LN new onset or flare during pregnancy increases the risks of
      preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and
      intrauterine growth restriction. Consequently, current recommendations advise
      that the affected woman achieve a stable remission of her renal disease for at
      least 6 months before conception. Hormonal and immune system changes in pregnancy
      may affect disease activity and progression, and published evidence suggests that
      there is an increased risk for a LN flare during pregnancy. The major goal of
      immunosuppressive therapy in pregnancy is control of disease activity with
      medications that are relatively safe for a growing fetus. Therefore, the use of
      mycophenolate mofetil, due to increasing evidence supporting its teratogenicity,
      is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs
      in proteinuric renal diseases toward the end of pregnancy, should be
      differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific
      condition clinically characterized by hypertension and proteinuria. These
      considerations present challenges that underscore the importance of a
      multidisciplinary team approach when caring for these patients, including a
      nephrologist, rheumatologist, and obstetrician who have experience with these
      pregnancy-related complications. This review discusses the pathogenesis, maternal
      and fetal risks, and management pertinent to SLE patients with new onset or a
      history of LN predating pregnancy.

PMID- 22879438
TI  - Onco-nephrology: the pathophysiology and treatment of malignancy-associated
      hypercalcemia.
AB  - Hypercalcemia complicates the course of 10%-30% of all patients with malignancies
      and can be a sign of very poor prognosis and advanced malignancy. Prompt
      recognition of the nonspecific signs and symptoms of hypercalcemia and
      institution of therapy can be lifesaving, affording the opportunity to address
      the underlying etiology. The mechanisms of malignancy-associated hypercalcemia
      generally fall into three categories: humoral hypercalcemia due to secreted
      factors (such as parathyroid-related hormone), local osteolysis due to tumor
      invasion of bone, and absorptive hypercalcemia due to excess vitamin D produced
      by malignancies. The mainstays of therapy for hypercalcemia are aggressive
      intravenous volume expansion with saline, bisphosphonate therapy, and perhaps
      loop diuretics. Adjunctive therapy may include calcitonin and corticosteroids. In
      refractory cases, gallium nitrate and perhaps denosumab are alternatives. In
      patients presenting with severe AKI, hemodialysis with a low-calcium bath can be
      effective. In most cases, therapy normalizes calcium levels and allows for
      palliation or curative therapy of the malignancy.

PMID- 22879439
TI  - Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be
      considered the drug of choice?
AB  - Severe lupus nephritis is an aggressive disease that requires an aggressive
      approach to treatment. Recent randomized clinical trials showed that
      mycophenolate mofetil compared favorably with cyclophosphamide (traditional
      approach) for remission induction. Consequently, mycophenolate mofetil is now
      commonly recommended as first-line therapy. Nevertheless, the role of
      mycophenolate mofetil in treating severe lupus nephritis is unclear, because such
      patients were excluded from these trials. With this limitation as background,
      this work addresses the question of mycophenolate mofetil for induction therapy
      for severe lupus nephritis. We performed a systematic review of the outcomes of
      treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide.
      Because no studies directly addressed this question, these data were extracted
      from the published literature or obtained by personal communications from
      investigators. There is no universally accepted definition, and therefore, severe
      lupus nephritis was arbitrarily defined by renal histology, resistance to
      therapy, or level of kidney function at presentation. For each trial analyzed, we
      determined the partial and complete remission rates. Long-term outcomes were
      compared when available. The pooled results suggest that mycophenolate mofetil
      and cyclophosphamide are equally effective in inducing remission of severe lupus
      nephritis. However, relapse rates and risk of developing ESRD were higher for
      mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short
      term, mycophenolate mofetil and cyclophosphamide are about equal in inducing
      remission. However, long-term outcomes suggest better preservation of kidney
      function and fewer relapses with cyclophosphamide therapy. Therefore,
      mycophenolate mofetil should not yet be considered the induction drug of choice
      for severe lupus nephritis.

PMID- 22879440
TI  - Onco-nephrology: renal toxicities of chemotherapeutic agents.
AB  - Despite dramatic improvements in patient survival and drug tolerability,
      nephrotoxicity remains an important complication of chemotherapy. Adverse renal
      effects occur because of innate drug toxicity and a number of patient- and drug
      related factors. To provide cutting edge care for these patients, nephrologists
      and oncologists must be familiar with the nephrotoxicity of these drugs,
      particularly their associated clinical and laboratory manifestations. Rapid
      diagnosis, targeted treatment, and supportive care are critical to improving care
      for these patients. Unfortunately, some patients who develop nephrotoxicity will
      be left with long-term complications such as chronic tubulopathies and CKD. Onco
      Nephrology is a new area that is rapidly expanding and requires a close working
      relationship between oncologists and nephrologists.

PMID- 22879441
TI  - Safety and feasibility of an exercise prescription approach to rehabilitation
      across the continuum of care for survivors of critical illness.
AB  - BACKGROUND: Survivors of critical illness can experience long-standing functional
      limitations that negatively affect their health-related quality of life. To date,
      no model of rehabilitation has demonstrated sustained improvements in physical
      function for survivors of critical illness beyond hospital discharge. OBJECTIVE:
      The aims of this study were: (1) to describe a model of rehabilitation for
      survivors of critical illness, (2) to compare the model to local standard care,
      and (3) to report the safety and feasibility of the program. DESIGN: This was a
      cohort study. METHODS: As part of a larger randomized controlled trial, 74
      participants were randomly assigned, 5 days following admission to the intensive
      care unit (ICU), to a protocolized rehabilitation program that commenced in the
      ICU and continued on the acute care ward and for a further 8 weeks following
      hospital discharge as an outpatient program. Exercise training was prescribed
      based on quantitative outcome measures to achieve a physiological training
      response. RESULTS: During acute hospitalization, 60% of exercise sessions were
      able to be delivered. The most frequently occurring barriers to exercise were
      patient safety and patient refusal due to fatigue. Point prevalence data showed
      patients were mobilized more often and for longer periods compared with standard
      care. Outpatient classes were poorly attended, with only 41% of the patients
      completing more than 70% of outpatient classes. No adverse events occurred.
      LIMITATIONS: Limitations included patient heterogeneity and delayed commencement
      of exercise in the ICU due to issues of consent and recruitment. CONCLUSIONS:
      Exercise training that commences in the ICU and continues through to an
      outpatient program is safe and feasible for survivors of critical illness. Models
      of care that maximize patient participation across the continuum of care warrant
      further investigation.

PMID- 22879442
TI  - Effectiveness of an early mobilization protocol in a trauma and burns intensive
      care unit: a retrospective cohort study.
AB  - BACKGROUND: Bed rest and immobility in patients on mechanical ventilation or in
      an intensive care unit (ICU) have detrimental effects. Studies in medical ICUs
      show that early mobilization is safe, does not increase costs, and can be
      associated with decreased ICU and hospital lengths of stay (LOS). OBJECTIVE: The
      purpose of this study was to assess the effects of an early mobilization protocol
      on complication rates, ventilator days, and ICU and hospital LOS for patients
      admitted to a trauma and burn ICU (TBICU). DESIGN: This was a retrospective
      cohort study of an interdisciplinary quality-improvement program. METHODS: Pre-
      and post-early mobility program patient data from the trauma registry for 2,176
      patients admitted to the TBICU between May 2008 and April 2010 were compared.
      RESULTS: No adverse events were reported related to the early mobility program.
      After adjusting for age and injury severity, there was a decrease in airway,
      pulmonary, and vascular complications (including pneumonia and deep vein
      thrombosis) post-early mobility program. Ventilator days and TBICU and hospital
      lengths of stay were not significantly decreased. LIMITATIONS: Using a historical
      control group, there was no way to account for other changes in patient care that
      may have occurred between the 2 periods that could have affected patient
      outcomes. The dose of physical activity both before and after the early mobility
      program were not specifically assessed. CONCLUSIONS: Early mobilization of
      patients in a TBICU was safe and effective. Medical, nursing, and physical
      therapy staff, as well as hospital administrators, have embraced the new culture
      of early mobilization in the ICU.

PMID- 22879443
TI  - Which prognostic factors for low back pain are generic predictors of outcome
      across a range of recovery domains?
AB  - BACKGROUND: Recovery from low back pain (LBP) is multidimensional and requires
      the use of multiple-response (outcome) measures to fully reflect these many
      dimensions. Predictive prognostic variables that are present or stable in all or
      most predictive models that use different outcome measures could be considered
      "universal" prognostic variables. OBJECTIVE: The aim of this study was to explore
      the potential of universal prognostic variables in predictive models for 4
      different outcome measures in patients with mechanical LBP. DESIGN: Predictive
      modeling was performed using data extracted from a randomized controlled trial.
      Four prognostic models were created using backward stepwise deletion logistic,
      Poisson, and linear regression. METHODS: Data were collected from 16 outpatient
      physical therapy facilities in 10 states. All 149 patients with LBP were treated
      with manual therapy and spine strengthening exercises until discharge. Four
      different measures of response were used: Oswestry Disability Index and Numeric
      Pain Rating Scale change scores, total visits, and report of rate of recovery.
      RESULTS: The set of statistically significant predictors was dependent on the
      definition of response. All regression models were significant. Within both forms
      of the 4 models, meeting the clinical prediction rule for manipulation at
      baseline was present in all 4 models, whereas no irritability at baseline and
      diagnosis of sprains and strains were present in 2 of 4 of the predictive models.
      LIMITATIONS: The primary limitation is that this study evaluated only 4 of the
      multiple outcome measures that are pertinent for patients with LBP. CONCLUSIONS:
      Meeting the clinical prediction rule was prognostic for all outcome measures and
      should be considered a universal prognostic predictor. Other predictive variables
      were dependent on the outcomes measure used in the predictive model.

PMID- 22879444
TI  - Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating
      data on polyphenol metabolism and pharmacokinetics in humans and experimental
      animals.
AB  - Phenol-Explorer, launched in 2009, is the only comprehensive web-based database
      on the content in foods of polyphenols, a major class of food bioactives that
      receive considerable attention due to their role in the prevention of diseases.
      Polyphenols are rarely absorbed and excreted in their ingested forms, but
      extensively metabolized in the body, and until now, no database has allowed the
      recall of identities and concentrations of polyphenol metabolites in biofluids
      after the consumption of polyphenol-rich sources. Knowledge of these metabolites
      is essential in the planning of experiments whose aim is to elucidate the effects
      of polyphenols on health. Release 2.0 is the first major update of the database,
      allowing the rapid retrieval of data on the biotransformations and
      pharmacokinetics of dietary polyphenols. Data on 375 polyphenol metabolites
      identified in urine and plasma were collected from 236 peer-reviewed publications
      on polyphenol metabolism in humans and experimental animals and added to the
      database by means of an extended relational design. Pharmacokinetic parameters
      have been collected and can be retrieved in both tabular and graphical form. The
      web interface has been enhanced and now allows the filtering of information
      according to various criteria. Phenol-Explorer 2.0, which will be periodically
      updated, should prove to be an even more useful and capable resource for
      polyphenol scientists because bioactivities and health effects of polyphenols are
      dependent on the nature and concentrations of metabolites reaching the target
      tissues. The Phenol-Explorer database is publicly available and can be found
      online at http://www.phenol-explorer.eu. Database URL: http://www.phenol
      explorer.eu.

PMID- 22879445
TI  - Lethal carbon monoxide poisoning in wood pellet storerooms--two cases and a
      review of the literature.
AB  - The installation of wood pellet heating as a cost-effective and climatically
      neutral source of energy for private households has increased steadily in recent
      years. We report two deaths that occurred within the space of about a year in
      wood pellet storerooms of private households in German-speaking countries and
      were investigated by forensic medical teams. This is the first report of
      fatalities in this special context as is shown in the literature review. Both
      victims died of carbon monoxide (CO) poisoning; one of the victims was a woman
      who was 4 months pregnant. Measurements at the scene detected life-threatening CO
      concentrations (7500 ppm, >500 ppm), which were not significantly reduced after
      ventilation of the storerooms as required by regulations. We carried out a series
      of experiments in order to confirm CO production by wood pellets. Thirty
      kilograms of freshly produced pellets from two different manufacturers were
      stored for 16 days in airtight containers at 26 degrees C with different relative
      humidities. CO concentrations between 3100 and 4700 ppm were measured in all
      containers. There were no notable differences between the wood pellet products or
      storage at different humidities. Emission of CO from wood pellets has already
      been described, but fatal accidents have previously been reported only in
      association with pellet transport on cargo ships or storage in silos. It is
      therefore a new finding that fatal accidents may also occur in the wood pellet
      storerooms of private households. We show that significant CO concentrations can
      build up even when these rooms are ventilated in accordance with the regulations
      and that such levels may cause the death of healthy persons, as described in the
      following. As the safety recommendations from the wood pellet industry are
      inadequate, we consider that further fatal accidents are likely to occur and
      recommend urgent revision of the safety regulations.

PMID- 22879446
TI  - Reciprocal peer review for quality improvement: an ethnographic case study of the
      Improving Lung Cancer Outcomes Project.
AB  - BACKGROUND: Peer review offers a promising way of promoting improvement in health
      systems, but the optimal model is not yet clear. We aimed to describe a specific
      peer review model-reciprocal peer-to-peer review (RP2PR)-to identify the features
      that appeared to support optimal functioning. METHODS: We conducted an
      ethnographic study involving observations, interviews and documentary analysis of
      the Improving Lung Cancer Outcomes Project, which involved 30 paired
      multidisciplinary lung cancer teams participating in facilitated reciprocal site
      visits. Analysis was based on the constant comparative method. RESULTS:
      Fundamental features of the model include multidisciplinary participation, a
      focus on discussion and observation of teams in action, rather than paperwork;
      facilitated reflection and discussion on data and observations; support to
      develop focused improvement plans. Five key features were identified as important
      in optimising this model: peers and pairing methods; minimising logistic burden;
      structure of visits; independent facilitation; and credibility of the process.
      Facilitated RP2PR was generally a positive experience for participants, but
      implementing improvement plans was challenging and required substantial support.
      RP2PR appears to be optimised when it is well organised; a safe environment for
      learning is created; credibility is maximised; implementation and impact are
      supported. DISCUSSION: RP2PR is seen as credible and legitimate by lung cancer
      teams and can act as a powerful stimulus to produce focused quality improvement
      plans and to support implementation. Our findings have identified how RP2PR
      functioned and may be optimised to provide a constructive, open space for
      identifying opportunities for improvement and solutions.

PMID- 22879447
TI  - Determinants of success of quality improvement collaboratives: what does the
      literature show?
AB  - CONTEXT: The apparent inconsistency between the widespread use of quality
      improvement collaboratives and the available evidence heightens the importance of
      thoroughly understanding the relative strength of the approach. More insight into
      factors influencing outcome would mean future collaboratives could be tailored in
      ways designed to increase their chances of success. This review describes
      potential determinants of team success and how they relate to effectiveness.
      METHOD: We searched Medline, CINAHL, Embase, Cochrane, and PsycINFO databases
      from January 1995 to June 2006. The 1995-2006 search was updated in June 2009.
      Reference lists of included papers were reviewed to identify additional papers.
      We included papers that were written in English, contained data about the
      effectiveness of collaboratives, had a healthcare setting, met our definition for
      collaborative, and quantitatively assessed a relationship between any determinant
      and any effect parameter. FINDINGS: Of 1367 abstracts identified, 23 papers
      (reporting on 26 collaboratives) provided information on potential determinants
      and their relationship with effectiveness. We categorised potential determinants
      of success using the definition for collaboratives as a template. Numerous
      potential determinants were tested, but only a few related to empirical
      effectiveness. Some aspects of teamwork and participation in specific
      collaborative activities enhanced short-term success. If teams remained intact
      and continued to gather data, chances of long-term success were higher. There is
      no empirical evidence of positive effects of leadership support, time and
      resources. CONCLUSIONS: These outcomes provide guidance to organisers,
      participants and researchers of collaboratives. To advance knowledge in this area
      we propose a more systematic exploration of potential determinants by applying
      theory and practice-based knowledge and by performing methodologically sound
      studies that clearly set out to test such determinants.

PMID- 22879448
TI  - The aging of the immune response in Drosophila melanogaster.
AB  - Senescence of functional immunity in invertebrates has been a topic of recent
      interest. Results from previous studies have been inconsistent with older adults
      exhibiting wide variation in response to infection. In the present study, we
      assayed the senescence of functional immune response using a large outbred
      population of Drososphila melanogaster as the model host and Serratia marcescens
      as the model pathogen. We assessed the effect of an individual's age, parental
      age, sex, and mating status on overall antibacterial immunity. We found an
      improvement of immunity with the progression of age with 13-day-old flies
      exhibiting lower bacterial load compared with 3-day-old flies. Parental age did
      not show consistent effects on the antibacterial immunity of the offspring.
      Neither mating status nor the sex of an individual had any significant effect on
      immune response.

PMID- 22879449
TI  - Can human biology allow most of us to become centenarians?
AB  - Life span is a topic of great interest in science, medicine and among the general
      public. How long people live has a profound impact on medical costs,
      intergenerational interactions, and the solvency of age-based entitlement
      programs around the world. These challenges are already occurring and the
      magnitude of their impact is, in part, proportional to the fraction of a
      population that lives the longest. Some demographic forecasts suggest that most
      babies born since the year 2000 will survive to their 100th birthday. If these
      forecasts are correct, then there is reason to fear that the financial solvency
      of even the most prosperous countries are in jeopardy. We argue here that human
      biology will preclude survival to age 100 for most people.

PMID- 22879450
TI  - Lower limb muscle weakness predicts use of a multiple- versus single-step
      strategy to recover from forward loss of balance in older adults.
AB  - BACKGROUND: Older adults compared with young adults have reduced strength and
      balance recovery ability. The purpose of the present study was to investigate
      whether age, sex, and/or lower limb strength predicted the stepping strategy used
      to recover from a forward loss of balance. METHODS: Ninety-five, community
      dwelling, older adults, aged 65-90 years, participated in the study. Loss of
      balance was induced by releasing participants from a static forward lean.
      Participants performed four trials at three initial lean magnitudes and were
      subsequently classified as using a single- or multiple-step strategy. Isometric
      strength of the ankle, knee, and hip joint flexors and extensors was assessed
      using a dynamometer. RESULTS: Univariate logistic regression revealed that a unit
      (ie, 1% body weight [BW] * height) decrease in ankle plantar flexion, knee
      extension, or hip flexion strength was associated with 1.7-2.5 times increased
      odds of adopting a multiple-step strategy. Women also had greater odds of
      requiring a multiple-step recovery strategy at the two greatest lean magnitudes.
      Forward stepwise logistic regression revealed that hip flexor strength in
      particular was influential as it was the primary predictor included in the
      logistic regression models at 20% and 25% BW lean magnitudes. CONCLUSIONS: Lower
      limb muscle weakness, especially of the hip flexors and knee extensors, was
      associated with increased odds of requiring multiple steps compared with single
      steps to recover from forward loss of balance across a range of initial lean
      magnitudes. Improved balance recovery ability might be achieved by targeting
      these muscle groups in falls prevention programs.

PMID- 22879451
TI  - Aggregate health burden and the risk of hospitalization in older persons post hip
      replacement surgery.
AB  - BACKGROUND: We sought to understand the association between aggregate health
      burden-chronic conditions, functionally limiting health problems and mental well
      being-and the likelihood of hospitalization among older persons post hip
      replacement surgery. METHODS: Eight hundred and twenty-eight Medicare recipients
      from three U.S. states completed a questionnaire 3 years postsurgery. Using
      administrative data (Medicare Provider Analysis and Review), participants were
      prospectively followed for 12 months postquestionnaire to capture
      hospitalizations. Using logistic regression, demographic, socioeconomic, and
      behavioral characteristics and medical comorbidities were considered as
      predictors. Subsequently, musculoskeletal (MSK) functional and geriatric problems
      were added as predictors, then mental well-being and activity limitations. Path
      analysis was employed to elucidate interrelationships between these predictors,
      investigating whether mediated effects through mental well-being and activity
      limitations were operational. RESULTS: Mean age was 76 years (range: 67-96); 63%
      were women; 23% had >=1 hospitalization(s). When medical comorbidity, MSK
      limitations, and geriatric problems were considered, each was independently
      associated with hospitalization (odds ratios: 1.3, 1.1, 1.2, respectively). When
      mental well-being and activity limitations were added, these variables were
      predictive of hospitalization (odds ratios: 1.2, 1.1, respectively), while MSK
      limitations and geriatric problems were no longer predictive. Path analysis
      results suggested that the influence of medical comorbidity and MSK and geriatric
      problems were mediated through mental well-being and activity limitations.
      CONCLUSIONS: Several health domains predict hospitalization, beyond and including
      medical comorbidity. Efforts aimed at delaying/minimizing hospitalizations in
      this population should consider an array of domains for potentially targeted
      intervention. These findings can serve as a baseline against which future
      research can assess the impact of changes to the health care system.

PMID- 22879452
TI  - Older driver training using video and global positioning system technology--a
      randomized controlled trial.
AB  - BACKGROUND: There is emerging evidence that older driver training programs with
      on-road instruction are more effective than driver education programs that are
      conducted only in the classroom. Although most programs have provided this
      additional in-vehicle training with a driving instructor and a dual-braked
      vehicle, technology could assist in providing this feedback. It was hypothesized
      that participants who received video and global positioning system (GPS) feedback
      (Video group) in addition to classroom education would improve to a greater
      extent than those who received a classroom-based course alone (Education) or
      Control participants. METHODS: Fifty-four participants (32 men and 22 women), 70
      89 years old, randomized to one of the three groups, completed the study. All
      participants underwent pre- and postintervention driving tests, in their own
      vehicle, on a standardized route, that were recorded with video and GPS
      equipment. The Video group met with a driving instructor to receive feedback on
      their driving errors in their preintervention driving test. A blinded assessor
      scored all driving tests in random order. RESULTS: The Video group significantly
      reduced their driving errors by 25% (p < .05) following the intervention, whereas
      the other two groups did not change significantly. Fifty-two percent of
      participants from the Video group improved their global safety rating, whereas
      only 5.3% in the Control and 22.2% in the Education groups did. CONCLUSIONS: This
      study suggests that direct driving feedback using video and GPS technology could
      be an effective and novel means to provide older driver education.

PMID- 22879453
TI  - Preventive effect of protein-energy supplementation on the functional decline of
      frail older adults with low socioeconomic status: a community-based randomized
      controlled study.
AB  - BACKGROUND: Chronic undernutrition is a common condition in older people with low
      socioeconomic status and is clearly an important component of frailty. However,
      it is uncertain whether protein-energy supplementation can prevent functional
      decline in this group. METHODS: Eighty-seven frail older adults (usual gait
      speed, <0.6 m/second; Mini Nutritional Assessment, <24) were enrolled in this
      randomized controlled trial. Participants were randomly assigned to either an
      intervention group, which was provided two 200-mL cans of commercial liquid
      formula (additional 400 kcal of energy, 25g of protein, 9.4g of essential amino
      acids, 400mL of water) per day for 12 weeks, or the controls group, which did not
      receive this supplement. The primary outcomes were the change of the Physical
      Functioning and Short Physical Performance Battery. Usual gait speed, timed up
      and-go test, hand grip strength, and one-legged stance were also measured as
      secondary outcome variables. RESULTS: Physical Functioning increased by 5.9% (1
      point) in the intervention group, although no change was observed in the control
      group (p =.052). Short Physical Performance Battery remained stable in the
      intervention group, although it decreased by 12.5% (1 point) in controls (p =
      .039). Usual gait speed decreased by 1.0% in the intervention group versus 11.3%
      (0.04 m/second) in controls (p = .039). Timed up-and-go improved by 7.2% (1.1
      seconds) in the intervention group and worsened by 3.4% (0.9 seconds) in controls
      (p = .038). There were no differences between groups in hand grip strength or one
      legged stance performance. CONCLUSIONS: The results indicate that protein-energy
      supplementation administered to frail older adults with low socioeconomic status
      shows evidence of reducing the progression of functional decline.

PMID- 22879454
TI  - The severity of urinary incontinence decreases health-related quality of life
      among community-dwelling elderly.
AB  - BACKGROUND: Urinary incontinence (UI) is an important geriatric syndrome that has
      been associated with a wide range of health-related outcomes. However, UI
      severity has rarely been examined in the context of a comprehensive geriatric
      assessment. Therefore, the aim of this study is to examine the association
      between UI severity and health-related quality of life (QoL) when frequent
      geriatric issues are taken into account. METHODS: We performed a cross-sectional
      study of 1,124 participants aged 70 y and older. UI was diagnosed when difficulty
      with urinary continence was reported, and its severity was assessed through a
      modified version of the Sandvik Index. Health-related QoL was measured using the
      SF-36, including its physical and mental component summaries. Multivariate linear
      regression was performed to determine the association between UI severity and
      health-related QoL. RESULTS: Prevalence of UI was 18%, and it was severe in 29.3%
      of cases. Severely incontinent subjects were older and had worse self-perceived
      health status, greater disability, and more depressive symptoms in comparison
      with continent participants or with those affected to a lesser degree.
      Multivariate regression analysis showed a significant inverse association between
      the physical component summaries and moderate (B = -4.54) as well as severe UI (B
      = -6.72). The mental component summaries showed similar results (B = -1.44 and 
      4.43, respectively). CONCLUSIONS: UI severity is associated with lower QoL scores
      in both its components. This association appears to be more important as severity
      increases. UI severity must be evaluated thoroughly in the elderly because of its
      potential adverse effects on physical and mental health.

PMID- 22879455
TI  - Facial appearance reflects human familial longevity and cardiovascular disease
      risk in healthy individuals.
AB  - BACKGROUND: As facial appearance can be readily quantified and skin tissue easily
      accessed, they could be valuable tools for determining how biological mechanisms
      influence tissue degeneration with age and, consequently, human health and
      lifespan. It is unknown, however, whether appearance reflects disease risk or
      lifespan independently of factors already known to associate with both health and
      appearance. METHODS: In a cross-sectional study, we compared the amount of skin
      wrinkling on a sun-protected site (upper inner arm) and the facial appearance of
      261 offspring (mean age 63.2 y) of nonagenarian siblings with 253 age-matched
      controls (mean age 62.7 y), all with no reported disease history. We next
      examined whether any appearance features that significantly associated with
      familial longevity also associated with the Framingham cardiovascular disease
      (CVD) risk score. All analyses were adjusted for chronological age, smoking,
      photodamage, and body mass index. RESULTS: Female and male offspring had reduced
      upper inner arm skin wrinkling (p = .03 and p < .001, respectively), and the male
      offspring looked 1.4 y younger than the controls (p = .002). There were no
      significant associations between CVD risk and upper inner arm skin wrinkling.
      Women in the lowest quartile of CVD risk looked more than 2 y younger for their
      age than those in higher risk quartiles (p = .002). Systolic blood pressure was
      the most significant (p = .004) CVD risk factor that was associated with
      perceived age in women. CONCLUSIONS: Facial appearance and skin wrinkling at a
      sun-protected site reflect the propensity to reach an extreme old age, and facial
      appearance reflects the risk of succumbing to CVD independently of chronological
      age, smoking, photodamage, and BMI.

PMID- 22879456
TI  - Late life leisure activities and risk of cognitive decline.
AB  - BACKGROUND: Studies concerning the effect of different types of leisure
      activities on various cognitive domains are limited. This study tests the
      hypothesis that mental, physical, and social activities have a domain-specific
      protection against cognitive decline. METHODS: A cohort of a geographically
      defined population in China was examined in 2003-2005 and followed for an average
      of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and
      older without cognitive or physical impairment at baseline, and their cognitive
      performances were tested at baseline and follow-up examinations. RESULTS: High
      level of mental activity was related to less decline in global cognition (beta = 
      .23, p < .01), language (beta = -.11, p < .05), and executive function (beta = 
      .13, p < .05) in ANCOVA models adjusting for age, gender, education, history of
      stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High
      level of physical activity was related to less decline in episodic memory (beta =
      -.08, p < .05) and language (beta = -.15, p < .01). High level of social activity
      was associated with less decline in global cognition (beta = -.11, p < .05).
      Further, a dose-response pattern was observed: although participants who did not
      engage in any of the three activities experienced a significant global cognitive
      decline, those who engaged in any one of the activities maintained their
      cognition, and those who engaged in two or three activities improved their
      cognition. The same pattern was observed in men and in women. CONCLUSIONS:
      Leisure activities in old age may protect against cognitive decline for both
      women and men, and different types of activities seem to benefit different
      cognitive domains.

PMID- 22879457
TI  - Four-dimensional blood flow-specific markers of LV dysfunction in dilated
      cardiomyopathy.
AB  - AIMS: Patients with mild heart failure (HF) who are clinically compensated may
      have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra
      ventricular flow patterns have been recognized in these subjects. We hypothesized
      that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller
      proportion of inflow volume passing directly to ejection and diminished the end
      diastolic preservation of the inflow kinetic energy (KE). METHODS AND RESULTS: In
      10 patients with dilated cardiomyopathy (DCM) (49 +/- 14 years, six females) and
      10 healthy subjects (44 +/- 17 years, four females), four-dimensional MRI
      velocity and morphological data were acquired. A previously validated method was
      used to separate the LV end-diastolic volume (EDV) into four flow components
      based on the blood's locations at the beginning and end of the cardiac cycle. KE
      was calculated over the cardiac cycle for each component. The EDV was larger (P =
      0.021) and the ejection fraction smaller (P < 0.001) in DCM compared with healthy
      subjects; the SV was equivalent (DCM: 77 +/- 19, healthy: 79 +/- 16 mL). The
      proportion of the total LV inflow that passed directly to ejection was smaller in
      DCM (P = 0.000), but the end-diastolic KE/mL of the direct flow was not different
      in the two groups (NS). CONCLUSION: Despite equivalent LVSVs, HF patients with
      mild LV remodelling demonstrate altered diastolic flow routes through the LV and
      impaired preservation of inflow KE at pre-systole compared with healthy subjects.
      These unique flow-specific changes in the flow route and energetics are
      detectable despite clinical compensation, and may prove useful as subclinical
      markers of LV dysfunction.

PMID- 22879458
TI  - Genome-wide identification of genes involved in raffinose metabolism in Maize.
AB  - The raffinose family oligosaccharides (RFOs), such as raffinose and stachyose,
      are synthesized by a set of distinct galactosyltransferases, which sequentially
      add galactose units to sucrose. The accumulation of RFOs in plant cells are
      closely associated with the responses to environmental factors, such as cold,
      heat and drought stresses. Systematic analysis of genes involved in the raffinose
      metabolism has not been reported to date. Searching the recently available
      working draft of the maize genome, six kinds of enzyme genes were speculated,
      which should encode all the enzymes involved in the raffinose metabolism in
      maize. Expression patterns of some related putative genes were analyzed. The
      conserved domains and phylogenetic relationships among the deduced maize proteins
      and their homologs isolated from other plant species were revealed. It was
      discovered that some of the key enzymes, such as galactinol synthase (ZmGolS5,
      ZmGolS45 and ZmGolS37), raffinose synthase (ZmRS1, ZmRS2, ZmRS3 and ZmRS10),
      stachyose synthase (ZmRS8) and beta-fructofuranosidase, are encoded by multiple
      gene members with different expression patterns. These results reveal the
      complexity of the raffinose metabolism and the existence of metabolic channels
      for diverse RFOs in maize and provide useful information for improving maize
      stress tolerance through genetic engineering.

PMID- 22879459
TI  - Antibiotic susceptibilities and resistance genes of Ureaplasma parvum isolated in
      South Africa.
AB  - OBJECTIVES: There is only limited information on the antimicrobial
      susceptibilities and resistance genes of Ureaplasma parvum in South Africa. This
      study was designed to detect and characterize resistance genes in U. parvum.
      METHODS: Fifteen U. parvum isolates were investigated employing the broth
      microdilution method (tetracycline, doxycycline, ofloxacin, erythromycin,
      azithromycin and josamycin). Gene analyses were performed on target regions of:
      tet(M); gyrA, gyrB, parC and parE; erm(A), erm(B), erm(C) and erm(E); msr(A),
      msr(B), msr(C) and msr(D); 23S rRNA operons; and L4 and L22 ribosomal proteins.
      RESULTS: Seven of the U. parvum isolates were fully susceptible to the
      antibiotics tested. Five strains exhibited resistance to tetracycline (MICs 16
      256 mg/L), one strain was resistant to ofloxacin (MIC 128 mg/L) and four strains
      were resistant to macrolides (MICs 128 mg/L); two strains showed dual resistance
      to tetracycline and erythromycin. The five tetracycline-resistant strains were
      found to have mosaic tet(M) genes, with one strain containing different specific
      regions to those previously described. Mutations in the L22 ribosomal protein
      were seen in three strains that were resistant to erythromycin (two strains) and
      erythromycin + azithromycin (one strain). For a further strain that was resistant
      to erythromycin and azithromycin, possible mechanisms of resistance remained
      elusive. CONCLUSIONS: This is the first report of quinolone, erythromycin and
      azithromycin resistance development in U. parvum from South Africa. A point
      mutation in parC (Pro-57 -> Leu) and two novel mutations in parE (Ile-73 -> Thr
      and a methionine insertion at codon 86) were found in an ofloxacin-resistant
      strain. The study reinforces the adaptability of U. parvum to develop resistance
      and acquire, modify and maintain transposon-located resistance genes.

PMID- 22879461
TI  - Vasculitis following HPV immunization.

PMID- 22879460
TI  - Mycobacterium indicus pranii (Mw)-mediated protection against visceral
      leishmaniasis: involvement of TLR4 signalling.
AB  - OBJECTIVES: The aim of this study was to characterize the antileishmanial
      activity of heat-killed Mycobacterium indicus pranii (Mw) alone or in combination
      with a subtoxic dose of amphotericin B [AMB(st)]. METHODS: Mw- and Mw + AMB(st)
      mediated antileishmanial activity was evaluated by microscopic counting of
      intracellular amastigotes in Giemsa-stained macrophages and real-time PCR
      analysis of inducible nitric oxide synthase (iNOS) expression and measurement of
      nitric oxide generation by Griess reagent. The relationship between Mw and Toll
      like receptor 4 (TLR4) signalling was studied by fluorescence-activated cell
      sorting, western blot and confocal microscopy. The effect of Mw alone or in
      combination with AMB(st) on the expression and production of interleukin (IL)-12,
      tumour necrosis factor-alpha, IL-10 and transforming growth factor-beta was
      analysed by real-time PCR and ELISA, respectively. RESULTS: Mw treatment alone or
      with AMB(st) caused a significant increase in TLR4 expression of L. donovani
      infected macrophages along with the activation of TLR4 downstream signalling,
      facilitating active nuclear translocation of nuclear factor kappaB (NF-kappaB).
      These events culminated in the up-regulation of the proinflammatory response,
      which was abrogated by treatment with TLR4-specific small-interfering RNA. In
      addition, this study demonstrates that this chemoimmunotherapeutic strategy
      confers protection against leishmanial pathogenesis via TLR4-dependent counter
      regulation of inducible nitric oxide synthase (iNOS) and arginase1 activity.
      CONCLUSIONS: These results provide a mechanistic understanding of Mw- or Mw +
      AMB(st)-mediated protection against leishmanial parasites within host
      macrophages.

PMID- 22879462
TI  - Rheumatoid arthritis and falls: the influence of disease activity.
AB  - OBJECTIVE: To examine the correlation between disease activity of RA and the risk
      of falling. METHODS: Seventy-eight patients were tested. Disease activity was
      measured with acute-phase reactants, autoantibodies, swollen and tender joint
      count (SJC28, TJC28), pain on a visual analogue scale (VAS pain), patient and
      evaluator global assessment of disease activity (PGA, EGA), HAQ disability index
      (HAQ-DI), 28-joint DAS (DAS-28) and the clinical and simple disease activity
      indexes (CDAI, SDAI). The risk of falling was evaluated by a fall assessment
      consisting of Tinetti test (TIT), timed get up and go test (TUG), chair-rising
      test (CRT), tandem walk and tandem stand test. RESULTS: During the last 12
      months, 26.9% of the participants reported a fall and 46.2% mentioned the fear of
      falling. The most evident link [Spearman's correlation (r(s))] with the results
      of the fall assessment was found in HAQ-DI (CRT: r(s) = 0.523, TUG: r(s) = 0.620,
      TIT: r(s) = -0.676), CDAI (CRT: r(s) = 0.460, TUG: r(s) = 0.504, TIT: r(s) = 
      0.472), VAS pain (CRT: r(s) = 0.441, TUG: r(s) = 0.616, TIT: r(s) = -0.548) PGA
      (CRT: r(s) = 0.473, TUG: r(s) = 0.577, TIT: r(s) = -0.520) and TJC (CRT: r(s) =
      0.488, TUG: r(s) = 0.394, TIT: r(s) = -0.385). Patients with higher disease
      activity achieved poorer results in the fall assessment. CONCLUSION: The
      strongest correlation with falls was evident for patient-reported outcomes. Pain
      seems to be the common ground of these parameters. At the same time, disease
      activity influences pain. The results suggest an increased attention towards the
      risk of falling with patients of higher levels of disease activity or pain, and
      physio- or ergotherapeutical interventions as needed.

PMID- 22879463
TI  - BLyS upregulation in Sjogren's syndrome associated with lymphoproliferative
      disorders, higher ESSDAI score and B-cell clonal expansion in the salivary
      glands.
AB  - OBJECTIVE: Primary SS is characterized by an increased risk of lymphoma in
      patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or
      mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels in SS
      related B-cell lymphoproliferative disorders were studied by integrating the
      results with the disease activity score and with molecular analyses of B-cell
      expansion in the salivary glands. METHODS: Seventy-six primary SS patients (with
      or without lymphoma or prelymphomatous manifestations), 56 HCV-related
      cryoglobulinaemic vasculitis patients and 55 controls were studied. s-BLyS and
      molecular analyses of B-cell expansion in the salivary gland tissues were
      performed. Patients with SS and persistent parotid swelling underwent parotid
      biopsy. RESULTS: s-BLyS differed between SS subgroups, higher levels being
      documented in patients with lymphoma or prelymphomatous manifestations vs SS
      without [1.85 (0.45-4.12) ng/ml vs 1.12 (0.56-1.98) ng/ml; P < 0.0001]. s-BLyS
      levels significantly correlated with the European League Against Rheumatism
      (EULAR) SS disease activity index (r = 0.62, P < 0.0001, Spearman's test). Clonal
      B-cell expansion in the salivary glands, but not polyclonal B-cell expansion, was
      associated with higher s-BLyS levels [1.98 (0.45-4.12) ng/ml vs 1.15 (0.56-3.25)
      ng/ml; P = 0.013)]. CONCLUSION: Higher s-BLyS levels and tissue clonal B-cell
      expansion characterize SS with B-cell lymphoproliferative disorders, even at
      prelymphomatous stages. This subgroup of SS patients showed the highest EULAR SS
      disease activity index scores. This represents a biologic rationale for targeting
      both clonal B-cell expansion and s-BLyS overproduction in SS.

PMID- 22879464
TI  - The early psoriatic arthritis screening questionnaire: a simple and fast method
      for the identification of arthritis in patients with psoriasis.
AB  - OBJECTIVE: Dermatologists usually see patients with psoriasis before arthritis
      develops, making them well placed to diagnose early PsA (ePsA). This study aimed
      to develop a rapid and robust screening questionnaire for predicting PsA in
      patients with psoriasis referred to a specialized joint dermatology-rheumatology
      combined clinic. METHODS: In all, 228 psoriasis patients naive to DMARD treatment
      were administered two screening questionnaire: the new Early ARthritis for
      Psoriatic patients (EARP) questionnaire and the existing Psoriatic Arthritis
      Screening and Evaluation (PASE) questionnaire. The diagnostic accuracy of the two
      questionnaires for the diagnosis of ePsA was compared by receiving operating
      characteristics curves. RESULTS: After psychometric analysis, a simplified
      questionnaire of 10 items was found to have good internal reliability (Cronbach's
      alpha = 0.83) and was much faster and simpler to administer than the PASE. Both
      the EARP and PASE questionnaires presented similar receiving operating
      characteristics curves (specificity 91.6 and 67.2 and sensitivity 85.2 and 90.7,
      respectively) in identifying ePsA patients by using the cut-off value of 3 for
      EARP-10 and the standard cut-off value of 44 for PASE. The CASPAR criteria for
      PsA were present in 61 (26.7%) of the patients at clinical presentation and in
      32.9% at 1-year follow-up, and the EARP score of >=3 correlated with clinically
      determined arthropathy by a rheumatologist. CONCLUSION: The EARP questionnaire is
      simple and fast to administer and proved robust for the identification of PsA in
      the dermatological setting. Dermatologists should consider the EARP for patients
      attending clinics, as it correlates well with early PsA diagnosis.

PMID- 22879465
TI  - Effectiveness of etanercept vs cyclophosphamide as treatment for patients with
      amyloid A amyloidosis secondary to rheumatoid arthritis.
AB  - OBJECTIVES: To compare the effectiveness of an alkylating agent with that of a
      biologic agent in the treatment of patients with amyloid A (AA) amyloidosis
      secondary to RA and to assess the association of the serum AA (SAA) 1.3 allele
      with treatment. METHODS: CYC and etanercept (ETN) were administered to 62 and 24
      RA patients, respectively, who were confirmed with biopsy as having AA
      amyloidosis. We evaluated whether the SAA1.3 allele, a factor indicating genetic
      risk and poor prognosis of Japanese RA patients with AA amyloidosis, influenced
      treatments and retrospectively analysed the effectiveness of both agents via
      statistical methods. RESULTS: Two treatment groups were similar, except for the
      SAA1.3 genotype (P = 0.015) and duration of AA amyloidosis since diagnosis (P <
      0.001). Also, patients given ETN had somewhat worse renal function, i.e. 24-h
      proteinuria (P = 0.02), at the initiation of treatment. ETN demonstrated greater
      effectiveness than CYC, as shown by significantly improved levels of serum CRP
      and serum albumin (both P < 0.01) and estimated glomerular filtration rate (eGFR;
      P = 0.032). ETN improved survival (P = 0.025), and the hazard ratios for the risk
      of death endpoint with eGFR and 24-h proteinuria were significant by P = 0.024
      and P = 0.025, respectively. The SAA1.3 allele did not affect the response to
      medications in AA amyloidosis secondary to RA. CONCLUSION: ETN treatment was more
      effective than CYC treatment, and CRP, albumin and eGFR may be valuable
      biomarkers for analysis. The SAA1.3 allele was not a factor affecting treatment
      in Japanese patients with AA amyloidosis secondary to RA.

PMID- 22879466
TI  - Current evidence of methotrexate efficacy in childhood chronic uveitis: a
      systematic review and meta-analysis approach.
AB  - OBJECTIVE: To summarize evidence regarding the effectiveness of MTX in the
      treatment of childhood autoimmune chronic uveitis (ACU). METHODS: A systematic
      search of articles between January 1990 and June 2011 was conducted using EMBASE,
      Ovid MEDLINE, Evidence-Based Medicine Reviews-ACP Journal Club, the Cochrane
      Library and EBM Reviews. Studies investigating the efficacy of MTX as a single
      immunosuppressant medication in the treatment of ACU refractory to therapy with
      topical treatment and/or systemic treatment in children (<=16 years) were
      eligible for inclusion. The primary outcome measure was the improvement of
      intraocular inflammation, expressed as Tyndall, as defined by the Standardization
      of Uveitis Nomenclature working group criteria. The effect measure for each study
      was the proportion of people classified as responders. We determined a combined
      estimate of the proportion of children in the eligible studies responding to MTX.
      RESULTS: The initial search identified 246 articles of which 52 were potentially
      eligible. Nine eligible articles, all retrospective chart reviews, remained in
      the analysis. The number of children in studies ranged from 3 to 25, and the dose
      of MTX varied from 7.5 to 30 mg/m2. Altogether, 95 of 135 children responded to
      MTX. The pooled analysis suggested that MTX has a favourable effect in the
      improvement of intraocular inflammation: the proportion of responding subjects
      was 0.73 (95% CI 0.66, 0.81). CONCLUSION: Although randomized controlled trials
      are needed, the available evidence supports the use of MTX in the treatment of
      childhood ACU: approximately three-quarters of patients on MTX can expect
      improvement in intraocular inflammation.

PMID- 22879468
TI  - An end to waste?

PMID- 22879473
TI  - U.S. science funding. Congress ready to extend budget at current levels.

PMID- 22879474
TI  - U.S. conflict regulations. Scientists sue to halt financial disclosure rule.

PMID- 22879476
TI  - Higher education. With eye to innovation, China revamps its universities.

PMID- 22879475
TI  - Oil resources. Are world oil's prospects not declining all that fast?

PMID- 22879477
TI  - Paleoanthropology. A new face reveals multiple lineages alive at the dawn of our
      genus Homo.

PMID- 22879478
TI  - Mycology. Attack of the clones.

PMID- 22879479
TI  - Higher education. Can Afghan universities recover from war, Taliban, and neglect?

PMID- 22879480
TI  - Profile: Joao Zilhao. Neandertal champion defends the reputation of our closest
      cousins.

PMID- 22879481
TI  - Predicting the next influenza virus.

PMID- 22879482
TI  - Steps forward for Greece.

PMID- 22879484
TI  - Mainstreaming systems science.

PMID- 22879486
TI  - Comment on "Impaired respiratory and body temperature control upon acute
      serotonergic neuron inhibition".
AB  - Ray et al. (Reports, 29 July 2011, p. 637) assume that clozapine-N4-oxide (CNO)
      represents a "biologically inert synthetic ligand" that selectively activates the
      M4 muscarinic receptor-based DREADD (designer receptor exclusively activated by a
      designer drug). In contrast, due to the redox cycling of CNO with clozapine and
      to their cell membrane permeability, CNO is biologically active and its
      conversion products are capable of undermining DREADD effects.

PMID- 22879488
TI  - Water management. Water sustainability for China and beyond.

PMID- 22879489
TI  - Virology. A henipavirus vaccine in sight.

PMID- 22879490
TI  - Chemistry. Uncovering the uranium-nitrogen triple bond.

PMID- 22879491
TI  - Cell biology. Precursor or charge supplier?

PMID- 22879492
TI  - Applied physics. A different angle on light communications.

PMID- 22879493
TI  - Climate change. Ice sheets in transition.

PMID- 22879495
TI  - Chemistry. Low-temperature oxidation of methane.

PMID- 22879494
TI  - Medicine. Leveraging shear stress to bust clots with nanoparticles.

PMID- 22879496
TI  - Retrospective. Elinor Ostrom (1933-2012).

PMID- 22879497
TI  - Working with waste. More treasure than trash. Introduction.

PMID- 22879498
TI  - Infographic: world of waste.

PMID- 22879500
TI  - Modern-day waste pickers.

PMID- 22879499
TI  - Garbology 101: getting a grip on waste.

PMID- 22879501
TI  - Finding a new way to go.

PMID- 22879502
TI  - Water reclamation going green.

PMID- 22879503
TI  - A better way to denitrify wastewater.

PMID- 22879504
TI  - Save pave the world.

PMID- 22879505
TI  - Getting minds out of the sewer.

PMID- 22879506
TI  - Taking the "waste" out of "wastewater" for human water security and ecosystem
      sustainability.
AB  - Humans create vast quantities of wastewater through inefficiencies and poor
      management of water systems. The wasting of water poses sustainability
      challenges, depletes energy reserves, and undermines human water security and
      ecosystem health. Here we review emerging approaches for reusing wastewater and
      minimizing its generation. These complementary options make the most of scarce
      freshwater resources, serve the varying water needs of both developed and
      developing countries, and confer a variety of environmental benefits. Their
      widespread adoption will require changing how freshwater is sourced, used,
      managed, and priced.

PMID- 22879507
TI  - Conversion of wastes into bioelectricity and chemicals by using microbial
      electrochemical technologies.
AB  - Waste biomass is a cheap and relatively abundant source of electrons for microbes
      capable of producing electrical current outside the cell. Rapidly developing
      microbial electrochemical technologies, such as microbial fuel cells, are part of
      a diverse platform of future sustainable energy and chemical production
      technologies. We review the key advances that will enable the use of
      exoelectrogenic microorganisms to generate biofuels, hydrogen gas, methane, and
      other valuable inorganic and organic chemicals. Moreover, we examine the key
      challenges for implementing these systems and compare them to similar renewable
      energy technologies. Although commercial development is already underway in
      several different applications, ranging from wastewater treatment to industrial
      chemical production, further research is needed regarding efficiency,
      scalability, system lifetimes, and reliability.

PMID- 22879508
TI  - Challenges in metal recycling.
AB  - Metals are infinitely recyclable in principle, but in practice, recycling is
      often inefficient or essentially nonexistent because of limits imposed by social
      behavior, product design, recycling technologies, and the thermodynamics of
      separation. We review these topics, distinguishing among common, specialty, and
      precious metals. The most beneficial actions that could improve recycling rates
      are increased collection rates of discarded products, improved design for
      recycling, and the enhanced deployment of modern recycling methodology. As a
      global society, we are currently far away from a closed-loop material system.
      Much improvement is possible, but limitations of many kinds--not all of them
      technological--will preclude complete closure of the materials cycle.

PMID- 22879509
TI  - Valorization of biomass: deriving more value from waste.
AB  - Most of the carbon-based compounds currently manufactured by the chemical
      industry are derived from petroleum. The rising cost and dwindling supply of oil
      have been focusing attention on possible routes to making chemicals, fuels, and
      solvents from biomass instead. In this context, many recent studies have assessed
      the relative merits of applying different dedicated crops to chemical production.
      Here, we highlight the opportunities for diverting existing residual biomass--the
      by-products of present agricultural and food-processing streams--to this end.

PMID- 22879510
TI  - Recycling of the #5 polymer.
AB  - Polypropylene (PP) is a widely used plastic with consumer applications ranging
      from food packaging to automotive parts, including car battery casings. To
      differentiate it from other recyclable plastics, it is designated as #5. Here,
      the factors contributing to PP recycling rates are briefly reviewed.
      Considerations include collection and separation efficiency, processing
      chemistry, and market dynamics for the products derived from recyclates.

PMID- 22879511
TI  - The challenges of reusing mining and mineral-processing wastes.
AB  - Mining and mineral-processing wastes are one of the world's largest chronic waste
      concerns. Their reuse should be included in future sustainable development plans,
      but the potential impacts on a number of environmental processes are highly
      variable and must be thoroughly assessed. The chemical composition and
      geotechnical properties of the source rock determine which uses are most
      appropriate and whether reuse is economically feasible. If properly evaluated,
      mining waste can be reused to reextract minerals, provide additional fuel for
      power plants, supply construction materials, and repair surface and subsurface
      land structures altered by mining activities themselves.

PMID- 22879512
TI  - Evolution of ocean temperature and ice volume through the mid-Pleistocene climate
      transition.
AB  - Earth's climate underwent a fundamental change between 1250 and 700 thousand
      years ago, the mid-Pleistocene transition (MPT), when the dominant periodicity of
      climate cycles changed from 41 thousand to 100 thousand years in the absence of
      substantial change in orbital forcing. Over this time, an increase occurred in
      the amplitude of change of deep-ocean foraminiferal oxygen isotopic ratios,
      traditionally interpreted as defining the main rhythm of ice ages although
      containing large effects of changes in deep-ocean temperature. We have separated
      the effects of decreasing temperature and increasing global ice volume on oxygen
      isotope ratios. Our results suggest that the MPT was initiated by an abrupt
      increase in Antarctic ice volume 900 thousand years ago. We see no evidence of a
      pattern of gradual cooling, but near-freezing temperatures occur at every glacial
      maximum.

PMID- 22879513
TI  - Divergent nematic susceptibility in an iron arsenide superconductor.
AB  - Within the Landau paradigm of continuous phase transitions, ordered states of
      matter are characterized by a broken symmetry. Although the broken symmetry is
      usually evident, determining the driving force behind the phase transition can be
      complicated by coupling between distinct order parameters. We show how
      measurement of the divergent nematic susceptibility of the iron pnictide
      superconductor Ba(Fe(1-x)Co(x))(2)As(2) distinguishes an electronic nematic phase
      transition from a simple ferroelastic distortion. These measurements also
      indicate an electronic nematic quantum phase transition near the composition with
      optimal superconducting transition temperature.

PMID- 22879514
TI  - Exceptional activity for methane combustion over modular Pd@CeO2 subunits on
      functionalized Al2O3.
AB  - There is a critical need for improved methane-oxidation catalysts to both reduce
      emissions of methane, a greenhouse gas, and improve the performance of gas
      turbines. However, materials that are currently available either have low
      activity below 400 degrees C or are unstable at higher temperatures. Here, we
      describe a supramolecular approach in which single units composed of a palladium
      (Pd) core and a ceria (CeO(2)) shell are preorganized in solution and then
      homogeneously deposited onto a modified hydrophobic alumina. Electron microscopy
      and other structural methods revealed that the Pd cores remained isolated even
      after heating the catalyst to 850 degrees C. Enhanced metal-support interactions
      led to exceptionally high methane oxidation, with complete conversion below 400
      degrees C and outstanding thermal stability under demanding conditions.

PMID- 22879515
TI  - Closed-loop control of epilepsy by transcranial electrical stimulation.
AB  - Many neurological and psychiatric diseases are associated with clinically
      detectable, altered brain dynamics. The aberrant brain activity, in principle,
      can be restored through electrical stimulation. In epilepsies, abnormal patterns
      emerge intermittently, and therefore, a closed-loop feedback brain control that
      leaves other aspects of brain functions unaffected is desirable. Here, we
      demonstrate that seizure-triggered, feedback transcranial electrical stimulation
      (TES) can dramatically reduce spike-and-wave episodes in a rodent model of
      generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce
      pathological brain patterns in drug-resistant patients.

PMID- 22879516
TI  - Fate-restricted neural progenitors in the mammalian cerebral cortex.
AB  - During development of the mammalian cerebral cortex, radial glial cells (RGCs)
      generate layer-specific subtypes of excitatory neurons in a defined temporal
      sequence, in which lower-layer neurons are formed before upper-layer neurons. It
      has been proposed that neuronal subtype fate is determined by birthdate through
      progressive restriction of the neurogenic potential of a common RGC progenitor.
      Here, we demonstrate that the murine cerebral cortex contains RGC sublineages
      with distinct fate potentials. Using in vivo genetic fate mapping and in vitro
      clonal analysis, we identified an RGC lineage that is intrinsically specified to
      generate only upper-layer neurons, independently of niche and birthdate. Because
      upper cortical layers were expanded during primate evolution, amplification of
      this RGC pool may have facilitated human brain evolution.

PMID- 22879517
TI  - The pulvinar regulates information transmission between cortical areas based on
      attention demands.
AB  - Selective attention mechanisms route behaviorally relevant information through
      large-scale cortical networks. Although evidence suggests that populations of
      cortical neurons synchronize their activity to preferentially transmit
      information about attentional priorities, it is unclear how cortical synchrony
      across a network is accomplished. Based on its anatomical connectivity with the
      cortex, we hypothesized that the pulvinar, a thalamic nucleus, regulates cortical
      synchrony. We mapped pulvino-cortical networks within the visual system, using
      diffusion tensor imaging, and simultaneously recorded spikes and field potentials
      from these interconnected network sites in monkeys performing a visuospatial
      attention task. The pulvinar synchronized activity between interconnected
      cortical areas according to attentional allocation, suggesting a critical role
      for the thalamus not only in attentional selection but more generally in
      regulating information transmission across the visual cortex.

PMID- 22879518
TI  - Epigenetic modification of liver mitochondrial DNA is associated with
      histological severity of nonalcoholic fatty liver disease.
AB  - OBJECTIVE & DESIGN: Nonalcoholic fatty liver disease (NAFLD) is a clinical
      condition that refers to progressive histological changes ranging from simple
      steatosis (SS) to nonalcoholic steatohepatitis (NASH). We evaluated the status of
      cytosine methylation (5mC) of liver mitochondrial DNA (mtDNA) in selected regions
      of the mtDNA genome, such as D-loop control region, and mitochondrially encoded
      NADH dehydrogenase 6 (MT-ND6) and cytochrome C oxidase I (MT-CO1), to contrast
      the hypothesis that epigenetic modifications play a role in the phenotypic
      switching from SS to NASH. METHODS: We studied liver biopsies obtained from
      patients with NAFLD in a case-control design; 45 patients and 18 near-normal
      liver-histology subjects. RESULTS: MT-ND6 methylation was higher in the liver of
      NASH than SS patients (p < 0.04) and MT-ND6 methylated DNA/unmethylated DNA ratio
      was significantly associated with NAFLD activity score (p < 0.02). Liver MT-ND6
      mRNA expression was significantly decreased in NASH patients (0.26 +/- 0.30)
      versus SS (0.74 +/- 0.48), p < 0.003, and the protein level was also diminished.
      The status of liver MT-ND6 methylation in NASH group was inversely correlated
      with the level of regular physical activity (R = -0.54, p < 0.02). Hepatic
      methylation levels of D-Loop and MT-CO1 were not associated with the disease
      severity. DNA (cytosine-5) methyltransferase 1 was significantly upregulated in
      NASH patients (p < 0.002). Ultrastructural evaluation showed that NASH is
      associated with mitochondrial defects and peroxisome proliferation. CONCLUSION:
      Hepatic methylation and transcriptional activity of the MT-ND6 are associated
      with the histological severity of NAFLD. Epigenetic changes of mtDNA are
      potentially reversible by interventional programs, as physical activity could
      modulate the methylation status of MT-ND6.

PMID- 22879520
TI  - Case report: Manual lymphatic drainage and kinesio taping in the secondary
      malignant breast cancer-related lymphedema in an arm with arteriovenous (A-V)
      fistula for hemodialysis.
AB  - Lymphedema is a dreaded complication of breast cancer treatment. The standard
      care for lymphedema is complex decongestive physiotherapy, which includes manual
      lymphatic drainage (MLD), short stretch bandaging, exercise, and skin care. The
      Kinesio Taping could help to improve lymphatic uptake. We reported a patient with
      unilateral secondary malignant breast cancer-related lymphedema and arteriovenous
      (A-V) fistula for hemodialysis happened in the same arm, and used kinesio taping,
      MLD, and exercise to treat this patient because no pressure could be applied to
      the A-V fistula. The 12-session therapy created an excellent effect. We do not
      think the kinesio taping could replace short stretch bandaging, but it could be
      another choice for contraindicating pressure therapy patients, and we should pay
      attention to wounds induced by kinesio tape. 

PMID- 22879519
TI  - The NOD2insC polymorphism is associated with worse outcome following ileal pouch
      anal anastomosis for ulcerative colitis.
AB  - BACKGROUND: Inflammatory complications after ileal pouch-anal anastomosis (IPAA)
      for ulcerative colitis (UC) are common. OBJECTIVE: To investigate whether genetic
      factors are associated with adverse pouch outcomes such as chronic pouchitis (CP)
      and a Crohn's disease-like (CDL) phenotype. DESIGN: 866 patients were recruited
      from three centres in North America: Mount Sinai Hospital (Toronto, Ontario,
      Canada), the Cleveland Clinic (Cleveland, Ohio, USA) and Penn State Milton S
      Hershey Medical Center (Hershey, Pennsylvania, USA). DNA and clinical and
      demographic information were collected. Subjects were classified into post
      surgical outcome groups: no chronic pouchitis (NCP), CP and CDL phenotype.
      RESULTS: Clinical and genetic data were available on 714 individuals. 487 (68.2%)
      were classified as NCP, 118 (16.5%) CP and 109 (15.3%) CDL. The presence of
      arthritis or arthropathy (p=0.02), primary sclerosing cholangitis (p=0.009) and
      duration of time from ileostomy closure to recruitment (p=0.001) were
      significantly associated with outcome. The NOD2insC (rs2066847) risk variant was
      the single nucleotide polymorphism (SNP) most significantly associated with pouch
      outcome (p=7.4*10(-5)). Specifically, it was associated with both CP and CDL in
      comparison with NCP (OR=3.2 and 4.3, respectively). Additionally, SNPs in NOX3
      (rs6557421, rs12661812), DAGLB (rs836518) and NCF4 (rs8137602) were shown to be
      associated with pouch outcome with slightly weaker effects. A multivariable risk
      model combining previously identified clinical (smoking status, family history of
      inflammatory bowel disease), serological (anti-Saccharomyces cerevisiae antibody
      IgG, perinuclear antineutrophil cytoplasmic antibody and anti-CBir1) and genetic
      markers was constructed and resulted in an OR of 2.72 (p=8.89*10(-7)) for NCP
      versus CP/CDL and 3.22 (p=4.11*10(-8)) for NCP versus CDL, respectively.
      CONCLUSION: Genetic polymorphisms, in particular, the NOD2insC risk allele, are
      associated with chronic inflammatory pouch outcomes among patients with UC and
      IPAA.

PMID- 22879521
TI  - End-of-life and palliative care education in US pharmacy schools.
AB  - The objective of this endeavor was to ascertain the current status of end-of-life
      and palliative care within the curriculum of US pharmacy schools and compare to a
      similar 1986 study. Additionally, responses to recent professional guidelines for
      pharmacy schools regarding end-of-life issues can be addressed. A fixed-choice
      survey was mailed to the 125 US pharmacy schools with a 49% response rate.
      Results revealed that the lecture format of teaching on end-of-life issues
      continues to be used today with an increase in offerings and greater
      participation by students than in 1986. Recently established guidelines and
      standards regarding end-of-life issues for pharmacy schools are being addressed,
      thus today's pharmacists should be better prepared to relate to patients with
      terminal illnesses and their families than in 1986. 

PMID- 22879522
TI  - Cost-effectiveness of the community-based management of severe acute malnutrition
      by community health workers in southern Bangladesh.
AB  - This study assessed the cost-effectiveness of adding the community-based
      management of severe acute malnutrition (CMAM) to a community-based health and
      nutrition programme delivered by community health workers (CHWs) in southern
      Bangladesh. The cost-effectiveness of this model of treatment for severe acute
      malnutrition (SAM) was compared with the cost-effectiveness of the 'standard of
      care' for SAM (i.e. inpatient treatment), augmented with community surveillance
      by CHWs to detect cases, in a neighbouring area. An activity-based cost model was
      used, and a societal perspective taken, to include all costs incurred in the
      programme by providers and participants for the management of SAM in both areas.
      Cost data were coupled with programme effectiveness data. The community-based
      strategy cost US$26 per disability-adjusted life year (DALY) averted, compared
      with US$1344 per DALY averted for inpatient treatment. The average cost to
      participant households for their child to recover from SAM in community treatment
      was one-sixth that of inpatient treatment. These results suggest that this model
      of treatment for SAM is highly cost-effective and that CHWs, given adequate
      supervision and training, can be employed effectively to expand access to
      treatment for SAM in Bangladesh. 

PMID- 22879523
TI  - New hope: community-based misoprostol use to prevent postpartum haemorrhage.
AB  - The wide gap in maternal mortality ratios worldwide indicates major inequities in
      the levels of risk women face during pregnancy. Two priority strategies have
      emerged among safe motherhood advocates: increasing the quality of emergency
      obstetric care facilities and deploying skilled birth attendants. The training of
      traditional birth attendants, a strategy employed in the 1970s and 1980s, is no
      longer considered a best practice. However, inadequate access to emergency
      obstetric care and skilled birth attendants means women living in remote areas
      continue to die in large numbers from preventable maternal causes. This paper
      outlines an intervention to address the leading direct cause of maternal
      mortality, postpartum haemorrhage. The potential for saving maternal lives might
      increase if community-based birth attendants, women themselves, or other
      community members could be trained to use misoprostol to prevent postpartum
      haemorrhage. The growing body of evidence regarding the safety and efficacy of
      misoprostol for this indication raises the question: if achievement of the fifth
      Millennium Development Goal is truly a priority, why can policy makers and
      women's health advocates not see that misoprostol distribution at the community
      level might have life-saving benefits that outweigh risks? 

PMID- 22879524
TI  - Building HIA approaches into strategies for green space use: an example from
      Plymouth's (UK) Stepping Stones to Nature project.
AB  - The health and well-being benefits of access to green space are well documented.
      Research suggests positive findings regardless of social group, however barriers
      exist that limit access to green space, including proximity, geography and
      differing social conditions. Current public health policy aims to broaden the
      range of environmental public health interventions through effective partnership
      working, providing opportunities to work across agencies to promote the use of
      green space. Health Impact Assessment (HIA) is a combination of methods and
      procedures to assess the potential health and well-being impacts of policies,
      developments and projects. It provides a means by which negative impacts can be
      mitigated and positive impacts can be enhanced, and has potential application for
      assessing green space use. This paper describes the application of a HIA approach
      to a multi-agency project (Stepping Stones to Nature--SS2N) in the UK designed to
      improve local green spaces and facilitate green space use in areas classified as
      having high levels of deprivation. The findings suggest that the SS2N project had
      the potential to provide significant positive benefits in the areas of physical
      activity, mental and social well-being. Specific findings for one locality
      identified a range of actions that could be taken to enhance benefits, and
      mitigate negative factors such as anti-social behaviour. The HIA approach proved
      to be a valuable process through which impacts of a community development/public
      health project could be enhanced and negative impacts prevented at an early
      stage; it illustrates how a HIA approach could enhance multi-agency working to
      promote health and well-being in communities. 

PMID- 22879525
TI  - Reactive oxygen species and sperm function--in sickness and in health.
AB  - The ability of spermatozoa to generate reactive oxygen species (ROS) has  been
      appreciated since the 1940s. It is a universal property of mature  spermatozoa
      from all mammalian species and a major contributor to the  oxidative stress
      responsible for defective sperm function. The mechanisms by  which oxidative
      stress limits the functional competence of mammalian  spermatozoa involve the
      peroxidation of lipids, the induction of oxidative DNA  damage, and the formation
      of protein adducts. ROS production in these cells  involves electron leakage from
      the sperm mitochondria, triggered by a  multitude of factors that impede electron
      flow along the electron transport  chain. The net result of mitochondrial ROS
      generation is to damage these  organelles and initiate an intrinsic apoptotic
      cascade, as a consequence of  which spermatozoa lose their motility, DNA
      integrity, and vitality. This  pathway of programmed senescence also results in
      the exteriorization of  phosphatidylserine, which may facilitate the silent
      phagocytosis of these  cells in the aftermath of insemination, in turn
      influencing the female tract  immune response to sperm antigens and future
      fertility. Despite the  vulnerability of sperm to oxidative stress, it is also
      clear that normal sperm  function depends on low levels of ROS generation in
      order to promote the  signal transduction pathways associated with capacitation.
      Modulators of ROS  generation by spermatozoa may therefore have clinical utility
      in regulating  the fertilizing capacity of these cells and preventing the
      development of  antisperm immunity. Achievement of these objectives will require
      a systematic  evaluation of pro- and antioxidant strategies in vivo and in vitro.

PMID- 22879526
TI  - Questions about spermatogonia posed and answered since 2000.
AB  - This review focuses on 3 important advances in our understanding of rodent 
      spermatogonial stem cells (SSC) that have emerged since 2000: the identity of 
      SSC, the existence of a SSC niche, and gene expression in spermatogonia. It is 
      now apparent that the original scheme, in which the A(single)  (A(s))
      spermatogonia are the only stem cells, may be too simple.  Rather, separation of
      pairs of A(paired) (A(pr))  spermatogonia into singles might also play a role in
      the steady state  situation. However, evidence that in the normal epithelium
      fragmentation of  chains of A(aligned) (A(al)) spermatogonia into smaller  clones
      also plays a role is not yet conclusive. New evidence presented during  the last
      decade indicates that the A(s),A(pr), and  A(al) (A(s,pr,al)) spermatogonia are
      not localized at random  over the tubule basal lamina, as originally assumed, but
      are restricted to  those areas that border on interstitial tissue and, in
      particular, to areas  containing venules and arterioles, suggesting a specific
      relationship of this  localization with a possible SSC niche. Finally, gene
      expression studies are  showing how both extrinsic factors produced by Sertoli
      cells and intrinsic  factors that are products of the germ cells act either to
      maintain progenitor  cells or to promote differentiation and the commitment to
      meiosis. Taken  together, this new knowledge adds to our understanding of the
      balance between  2 opposing forces: one promoting the undifferentiated state and
      the other  promoting the commitment to meiosis and differentiation that is
      essential for  spermatogenesis to proceed.

PMID- 22879527
TI  - The genetics of male fertility--from basic science to clinical evaluation.
AB  - Our understanding of male fertility has increased dramatically over the  past
      several decades, in large part because of advances in technology and the  ability
      to rapidly analyze large quantities of high-resolution genetic data.  These
      research efforts have led to an understanding of some of the genes  involved in
      male fertility and have enabled us to test for defects in these  genes that
      result in infertility in men. However, our understanding of male  fertility
      remains far from comprehensive, and many genes involved in male  fertility likely
      remain to be identified and their mechanisms of action  elucidated. This can only
      be accomplished through continued, persistent  investigations using cutting-edge
      technologies. In this review, we discuss the  history of genetic testing and how
      it applies to male fertility, from the  identification of the sex chromosomes at
      the turn of the century to  classification of single-nucleotide polymorphisms
      that may result in  infertility and are the crux of modern genetic analysis. We
      discuss the  genetic testing methodologies traditionally used for genetic
      assessment of  infertile males, including karyotype analysis, sperm fluorescence
      in situ  hybridization, and polymerase chain reaction-based testing for Y 
      chromosomal evaluation, as well as cutting-edge genetic testing methodologies 
      using microarrays and whole-genome sequencing, permitting analysis at a 
      nucleotide-level resolution. Finally, we describe our vision of the future of 
      genetic testing in the setting of male infertility, culminating in truly 
      personalized medicine for each affected infertile male.

PMID- 22879529
TI  - Management of erectile dysfunction: great progress, greater promise.
AB  - Sexual medicine, exemplified by the management of erectile dysfunction, is  a
      traditional pillar of andrology. Erectile dysfunction has received the  greatest
      attention within the specialty area and its management models the  progress of
      the field more generally. This review provides a perspective of  the history and
      contemporary practice of erectile dysfunction management,  highlighting aspects
      of basic science research, epidemiology, and clinical  care. Furthermore, the
      impact of this field as a major health concern in  correlation with basic aspects
      of wellness and disease is acknowledged. The  field continues to evolve as a
      legitimate discipline in medicine and is worthy  of ongoing scientific support
      and activity.

PMID- 22879528
TI  - Aging and declining testosterone: past, present, and hopes for the future.
AB  - As men age, serum testosterone (T) levels decline, whereas serum  luteinizing
      hormone (LH) levels increase somewhat or remain unchanged.  Age-related
      reductions in T levels may be associated with alterations in body  composition;
      energy level; muscle strength; physical, sexual, and cognitive  functions; and
      mood. The predominant contributor to the decline in serum T  levels is the
      decreased ability of the aging testes to make T. As in humans,  the Brown Norway
      rat demonstrates age-related reductions in serum T levels in  the setting of
      unchanged or modestly increased serum LH levels. In this rat  model, the ability
      of aged Leydig cells, the terminally differentiated  T-producing cells of the
      testis, to produce T in response to LH stimulation is  significantly diminished.
      This review begins with a discussion of what is  known of the molecular
      mechanisms by which T synthesis declines with Leydig  cell aging. It concludes
      with a brief history of T replacement therapy,  current guidelines, controversies
      related to T replacement therapy in older  men, and proposed future clinical
      directions.

PMID- 22879530
TI  - Evolution of the Journal of Andrology and a bright future for Andrology.

PMID- 22879531
TI  - Parting messages from current and former editors of the Journal of Andrology.
AB  - The proposal to produce this final commemorative issue for the Journal  of
      Andrology arose during our regular discussions as current editors soon  after it
      was announced that the Journal would complete its own life  course and merge into
      a new publication (to be named Andrology) with  the International Journal of
      Andrology. We considered the momentous  occasion to be one that should be
      celebrated with an enduring tribute in  recognition of the Journal's exceptional
      33-year existence. Among the  various contributions sought for inclusion in this
      issue, we envisioned an  article assembling collected short essays from all
      living former editors  drawing on notable events and highlights, if not less well
      known challenges  and successes arising during their editorship eras. We thought
      that any such  production of musings, viewpoints, and most of all words of wisdom
      from those  who have had major roles in the direction and accomplishments of the 
      Journal would offer an illuminating read for the society's members  and friends
      and provide all readers another venue to share in and enjoy the  Journal's great
      history.   We are enthralled to have gathered these collections, all personal 
      compositions of the former editors-in-chief, and for their effort that has 
      helped us complete this special endeavor we express to them our tremendous 
      gratitude. Serving as the Journal's last editors, we are also  grateful to
      contribute our essay at the very end as part of this joyous  chronicle.

PMID- 22879532
TI  - Special Section: Commemorating the Journal of Andrology's Distinguished History.

PMID- 22879533
TI  - The UK transcatheter aortic valve implantation registry; one of the suite of
      registries hosted by the National Institute for Cardiovascular Outcomes Research
      (NICOR).
AB  - This registry was set up to create a comprehensive record of all TAVI procedures
      performed in the United Kingdom since the introduction of the technique in 2007,
      to help drive quality improvement and provide data for research. Funding is
      independent of industry. All hospitals in the UK provide data for every
      consecutive patient where TAVI was attempted. The dataset includes variables
      defining patient demographic features, indications, procedural details and
      outcomes up to the time of hospital discharge. There are variables for follow up
      at 1 and 3 years assessing symptoms and life status. An updated dataset will be
      collected from 2013. Mortality is tracked centrally. Data entry is performed by
      clinical staff and data clerks. No external validation. The data are available
      for research by application to the UK TAVI Steering Group using a data sharing
      agreement which can be obtained at NICOR (www.ucl.ac.uk/nicor/).

PMID- 22879534
TI  - Heliox increases quadriceps muscle oxygen delivery during exercise in COPD
      patients with and without dynamic hyperinflation.
AB  - Some reports suggest that heliox breathing during exercise may improve peripheral
      muscle oxygen availability in patients with chronic obstructive pulmonary disease
      (COPD). Besides COPD patients who dynamically hyperinflate during exercise
      (hyperinflators), there are patients who do not hyperinflate (non
      hyperinflators). As heliox breathing may differently affect cardiac output in
      hyperinflators (by increasing preload and decreasing afterload of both
      ventricles) and non-hyperinflators (by increasing venous return) during exercise,
      it was reasoned that heliox administration would improve peripheral muscle oxygen
      delivery possibly by different mechanisms in those two COPD categories. Chest
      wall volume and respiratory muscle activity were determined during constant-load
      exercise at 75% peak capacity to exhaustion, while breathing room air or normoxic
      heliox in 17 COPD patients: 9 hyperinflators (forced expiratory volume in 1 s =
      39 +/- 5% predicted), and 8 non-hyperinflators (forced expiratory volume in 1 s =
      48 +/- 5% predicted). Quadriceps muscle blood flow was measured by near-infrared
      spectroscopy using indocyanine green dye. Hyperinflators and non-hyperinflators
      demonstrated comparable improvements in endurance time during heliox (231 +/- 23
      and 257 +/- 28 s, respectively). At exhaustion in room air, expiratory muscle
      activity (expressed by peak-expiratory gastric pressure) was lower in
      hyperinflators than in non-hyperinflators. In hyperinflators, heliox reduced end
      expiratory chest wall volume and diaphragmatic activity, and increased arterial
      oxygen content (by 17.8 +/- 2.5 ml/l), whereas, in non-hyperinflators, heliox
      reduced peak-expiratory gastric pressure and increased systemic vascular
      conductance (by 11.0 +/- 2.8 ml.min(-1).mmHg(-1)). Quadriceps muscle blood flow
      and oxygen delivery significantly improved during heliox compared with room air
      by a comparable magnitude (in hyperinflators by 6.1 +/- 1.3 ml.min(-1).100 g(-1)
      and 1.3 +/- 0.3 ml O(2).min(-1).100 g(-1), and in non-hyperinflators by 7.2 +/-
      1.6 ml.min(-1).100 g(-1) and 1.6 +/- 0.3 ml O(2).min(-1).100 g(-1),
      respectively). Despite similar increase in locomotor muscle oxygen delivery with
      heliox in both groups, the mechanisms of such improvements were different: 1) in
      hyperinflators, heliox increased arterial oxygen content and quadriceps blood
      flow at similar cardiac output, whereas 2) in non-hyperinflators, heliox improved
      central hemodynamics and increased systemic vascular conductance and quadriceps
      blood flow at similar arterial oxygen content.

PMID- 22879535
TI  - Comparison of the Gibbs and Suga formulations of cardiac energetics: the demise
      of "isoefficiency".
AB  - Two very different sorts of experiments have characterized the field of cardiac
      energetics over the past three decades. In one of these, Gibbs and colleagues
      measured the heat production of isolated papillary muscles undergoing isometric
      contractions and afterloaded isotonic contractions. The former generated roughly
      linear heat vs. force relationships. The latter generated enthalpy-load
      relationships, the peak values of which occurred at or near peak isometric force,
      i.e., at a relative load of unity. Contractile efficiency showed a pronounced
      dependence on afterload. By contrast, Suga and coworkers measured the oxygen
      consumption (Vo(2)) while recording the pressure-volume-time work loops of blood
      perfused isolated dog hearts. From the associated (linear) end-systolic pressure
      volume relations they derived a quantity labeled pressure-volume area (PVA),
      consisting of the sum of pressure-volume work and unspent elastic energy and
      showed that this was linearly correlated with Vo(2) over a wide range of
      conditions. This linear dependence imposed isoefficiency: constant contractile
      efficiency independent of afterload. Neither these data nor those of Gibbs and
      colleagues are in dispute. Nevertheless, despite numerous attempts over the
      years, no demonstration of either compatibility or incompatibility of these
      disparate characterizations of cardiac energetics has been forthcoming. We
      demonstrate that compatibility between the two formulations is thwarted by the
      concept of isoefficiency, the thermodynamic basis of which we show to be
      untenable.

PMID- 22879536
TI  - Cognitive impairment during 5 m water immersion.
AB  - Experimental data document that human cognition remains intact down to 6 m water
      immersion. This, however, is difficult to reconcile with introspective
      observations from experienced divers, who report cognitive impairments. We
      hypothesized that the discrepancy might be related to the fact that previous
      experiments assessed abstract cognitive skills, such as mental arithmetic, which
      might be less sensitive to immersion than performance-related cognitive skills,
      such as planning of behavior that is adequate for a given situation. Moreover,
      previous studies did not control for the effects of water viscosity on subjects'
      response times. To address these issues, the present study evaluated performance
      related cognitive skills based on subjects' isometric responses. Forty-eight
      subjects were tested in 5 m under water and on dry land using multiple choice
      reaction tasks, a tracking task, and a combination of both. Sustained attention
      was also registered, and subjective workload was assessed by questionnaire. We
      found that a subject's cognitive performance was degraded under water by 9%,
      independent of task type and equally under single- and dual-task conditions.
      Sustained attention was reduced under water by 11% and tracking by 48%. The
      observed deficits were not correlated, which suggests multiple independent
      effects of immersion. Our findings support the hypothesis that performance
      related cognitive skills are affected already by shallow-water immersion. Since
      no such deficits were observed in a companion study just below the water's
      surface, the present findings are probably due to increased ambient pressure.

PMID- 22879537
TI  - Cross-reactivity of tapentadol specimens with DRI methadone enzyme immunoassay.
AB  - A substantial incidence of positive methadone screens for pain management urine
      specimens using a commercial enzyme immunoassay (EIA) was observed in the absence
      of a methadone prescription, with negative methadone confirmation by ultra
      performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS).
      Tapentadol was the only common prescription among the investigated specimens.
      Tapentadol or one of its three major metabolites was tested at various
      concentrations (100-200,000 ng/mL) against the DRI EIAs for methadone and
      methadone metabolite, to evaluate cross-reactivity. Ninety-seven authentic
      tapentadol urine specimens that produced false-positive methadone EIA results
      (cutoff = 130 ng/mL) were analyzed for methadone and tapentadol in compound
      specific UPLC-MS-MS confirmation tests. Tapentadol, tapentadol glucuronide,
      tapentadol sulfate and N-desmethyltapentadol exhibited cross-reactivity with the
      methadone EIA at 6,500 (2.2%), 25,000 (0.6%), 3,000 (4.4%) and 20,000 ng/mL
      (0.9%), respectively. No cross-reactivity was observed with the methadone
      metabolite 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine EIA. All authentic
      urine specimens were confirmed to be negative for methadone, but positive for
      tapentadol and all monitored metabolites. Individual concentrations indicated
      that separate or combined urinary concentrations of tapentadol and its conjugates
      may produce false-positive methadone screens through cross-reactivity with the
      methadone immunoassay. The potential for false-positive results for methadone EIA
      screening of urine specimens associated with tapentadol prescriptions should be
      considered when interpreting results.

PMID- 22879538
TI  - A humanized single-chain antibody against beta 3 integrin inhibits pulmonary
      metastasis by preferentially fragmenting activated platelets in the tumor
      microenvironment.
AB  - Platelets play a supportive role in tumor metastasis. Impairment of platelet
      function within the tumor microenvironment may provide a clinically useful
      approach to inhibit metastasis. We developed a novel humanized single-chain
      antibody (scFv Ab) against integrin GPIIIa49-66 (named A11) capable of lysing
      activated platelets. In this study, we investigate the effect of A11 on the
      development of pulmonary metastases. In the Lewis lung carcinoma (LLC) metastatic
      model, A11 decreases the mean number of surface nodules and mean volume of
      pulmonary nodules. It protects against lung metastases in a time window that
      extended 4 hours before and 4 hours after the IV injection of LLCs. Coinjection
      of GPIIIa49-66 albumin reverses the antimetastatic activity of A11 in the B16
      melanoma model, consistent with the pathophysiologic relevance of the platelet
      GPIIIa49-66 epitope. Significantly, A11 had no effect on angiogenesis using both
      in vitro and in vivo assays. The underlying molecular mechanisms are a
      combination of inhibition of each of the following interactions: between
      activated platelets and tumor cells, platelets and endothelial cells, and
      platelets and monocytes, as well as disaggregation of an existing platelet/tumor
      thrombus. Our observations may provide a novel antimetastatic strategy through
      lysing activated platelets in the tumor microenvironment using humanized anti
      GPIIIa49-66 scFv Ab.

PMID- 22879539
TI  - High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in
      other non-Langerhans cell histiocytoses.
AB  - Histiocytoses are rare disorders of unknown origin with highly heterogeneous
      prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis
      (LCH). We investigated the frequency of BRAF mutations in several types of
      histiocytoses. Histology from 127 patients with histiocytoses were reviewed.
      Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA
      extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease
      (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma,
      xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic
      xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients,
      respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were
      detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other
      histiocytoses. Four patients with ECD died of disease. The high frequency of
      BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment
      with vemurafenib should be investigated in patients with malignant BRAF(V600E)
      histiocytosis.

PMID- 22879540
TI  - Diagnosis and management of acute myeloid leukemia in children and adolescents:
      recommendations from an international expert panel.
AB  - Despite major improvements in outcome over the past decades, acute myeloid
      leukemia (AML) remains a life-threatening malignancy in children, with current
      survival rates of ~70%. State-of-the-art recommendations in adult AML have
      recently been published in this journal by Dohner et al. The primary goal of an
      international expert panel of the International BFM Study Group AML Committee was
      to set standards for the management, diagnosis, response assessment, and
      treatment in childhood AML. This paper aims to discuss differences between
      childhood and adult AML, and to highlight recommendations that are specific to
      children. The particular relevance of new diagnostic and prognostic molecular
      markers in pediatric AML is presented. The general management of pediatric AML,
      the management of specific pediatric AML cohorts (such as infants) or subtypes of
      the disease occurring in children (such as Down syndrome related AML), as well as
      new therapeutic approaches, and the role of supportive care are discussed.

PMID- 22879542
TI  - Training young cardiac surgeons in developing countries.

PMID- 22879541
TI  - A3669G polymorphism of glucocorticoid receptor is a susceptibility allele for
      primary myelofibrosis and contributes to phenotypic diversity and blast
      transformation.
AB  - The frequency of A3669G single nucleotide polymorphism (SNP) of human
      glucocorticoid receptor has been reported increased in polycythemia vera. We
      investigated the frequency of A3669G SNP and its impact on disease phenotype and
      progression in 499 patients with primary myelofibrosis (PMF). The distribution of
      the A3669G allele differed between PMF patients and 2 healthy control populations
      (odds ratio, 1.6 and 1.8). The variant allele at the homozygous state (G/G) was
      associated with higher white blood cell count, larger spleen index, and higher
      frequency of circulating CD34(+) cells at diagnosis. The latter association
      remained significant after correction for the JAK2V617F genotype. In patients
      JAK2V617F mutated, the G/G genotype was associated with shorter overall survival
      (77.6 months vs 298 months, P = .049) and blast transformation (BT)-free survival
      (76.7 months vs 261 months; P = .018). The latter association remained
      significant after correction for the known BT risk factors, such as age, sex,
      white blood cell count, percentage of blasts, IPSS prognostic score, and
      homozygosity for JAK2V617F (hazard ratio = 3.3; P = .006). In conclusion, the
      glucocorticoid receptor A3669G is a susceptibility allele for PMF: it contributes
      to confer the phenotype of excess myeloproliferation, and it cooperates with the
      JAK2V617F mutation in determining BT.

PMID- 22879543
TI  - Return to work after coronary artery bypass in patients aged under 50 years.
AB  - BACKGROUND: This study was designed to identify factors associated with return to
      work and quality of life in patients undergoing primary coronary artery bypass at
      age <50 years. METHODS: 172 patients<50-years old underwent primary coronary
      artery bypass between January 2000 and December 2006. Predictors of return to
      work were analysed from variables in a prospectively collected database and on
      follow-up by the SF-36 questionnaire in 129 (75%) patients. RESULTS: 136 (79%)
      patients were working prior to surgery. The educational level was: primary 14.5%,
      secondary 47%, trade 22%, tertiary 13%, and postgraduate 3%. Type of occupation
      was blue collar 51%, white collar 41%, pensioner 27%, and unspecfied 8%. The mean
      follow-up was 86.4+/-23.4 months. One hundred and twenty-six (69%) patients
      attended cardiac rehabilitation. Forty (23%) patients experienced recurrence of
      symptoms; 11 (6%) required reintervention. One hundred and twenty-seven (93%)
      patients returned to work postoperatively. Univariate predictors of return to
      work were male sex, blue-collar work, and working prior to surgery. Independent
      predictors of return to work were working prior to surgery and blue-collar work.
      Patients who returned to work had significantly higher scores in all 8 domains on
      the SF36-Questionnaire compared to those who did not return to work. CONCLUSIONS:
      Preoperative employment and blue collar occupation were associated with a higher
      rate of return to work after coronary artery bypass in patients of working age.
      Patients who returned to work had significantly better measured quality of life
      than those who did not.

PMID- 22879544
TI  - Choice of conduit for coronary artery bypass grafting in poor ventricles.
AB  - BACKGROUND: advantages in the use of arterial grafts for coronary artery
      revascularizations have been reported previously. OBJECTIVES: we aimed to compare
      the outcome and survival rates of different conduits in patients with poor
      ventricular function (ejection fraction<30%). METHODS: in a 10-year period, 979
      patients with an ejection fraction<30%, who underwent isolated first-time
      coronary artery bypass grafting, were divided into in 3 groups: (A) total
      arterial grafts (n=257), (B) total vein grafts (n=76), and (C) left internal
      mammary artery and vein grafts (n=610). Multivariate logistic regression was used
      to assess the effect of graft type on mortality, while adjusting for patient and
      disease characteristics. Hospital mortality and 5-year survival rates were
      compared among the groups. RESULTS: hospital mortality was 8.9% for group A,
      11.8% for group B, and 5.7% for group C. Mortality at 5 years was 27.2% for group
      A, 42.3% for group B, and 28.7% for group C. After risk adjustment, hospital
      mortality and mid- and long-term mortality showed no significant differences
      among the groups. CONCLUSIONS: patients with poor ventricular function have a
      high mortality rate in both the short- and long-term with any type of conduit.
      Mortality rates with total arterial grafts and vein plus arterial grafts were
      comparable before and after risk adjustment.

PMID- 22879545
TI  - Cardiac surgery in cases of myeloproliferative neoplasm: risk factor for stroke.
AB  - OBJECTIVES: a history of myeloproliferative neoplasms is considered to increase
      the risks in cardiac surgery. In patients with myeloproliferative neoplasms,
      increased rates of perioperative infections and thromboembolic complications are
      suspected, but studies analyzing the impact of myeloproliferative neoplasms on
      results after cardiac surgery are lacking. METHODS: 13 patients with the
      diagnosis of myeloproliferative neoplasm underwent cardiac surgery. These
      patients were matched to 36 controls. Matching criteria consisted of sex, age,
      diagnosis, and comorbidities. Patients were analyzed regarding laboratory
      parameters, blood transfusion demands, morbidity, and mortality. RESULTS:
      compared to controls, patients with myeloproliferative neoplasms demonstrated a
      significantly lower body-mass index (p<0.01), creatinine (p=0.024), prothrombin
      time (p=0.001), and urea level (p=0.012). The perioperative leukocyte response
      (p=0.03) was ameliorated, and platelet counts (p<0.02) increased. Patients with
      myeloproliferative neoplasms had a reduced need for erythrocyte concentrates (54%
      vs. 86%, p=0.047) but increased need for plasma and thrombocytes (15% vs. 0%,
      p=0.07). Patients with myeloproliferative neoplasms had a significantly increased
      incidence of thromboembolic events compared to controls (31% vs. 3%, p=0.014).
      Hospital mortality remained at zero, but mid-term survival was lower in patients
      with myeloproliferative neoplasms (p=0.078). CONCLUSIONS: myeloproliferative
      neoplasm as a concomitant diagnosis increases the risk of thromboembolic
      complications during cardiac surgery. Plasma and platelet substitutions have to
      be administered, although strokes were not associated with hemostatic treatment.

PMID- 22879546
TI  - Survival after surgical repair of ischemic ventricular septal rupture.
AB  - OBJECTIVES: We reviewed our results and experience over a 14-year period to
      identify predictors of outcome following surgical repair of postinfarction
      ventricular septal rupture. METHODS: A retrospective review was carried over a 14
      year period. All patients had surgical repair of a postinfarction ventricular
      septal rupture. Patient demographics, perioperative variables, and survival data
      were collected. Logistic regression identified independent predictors of 30-day
      mortality. Multivariate analysis determined the effects of independent risk
      factors on survival. RESULTS: Surgery for postinfarction ventricular septal
      rupture was carried out on 59 patients. The median age was 69 years, and 69% were
      male. In 54% of patients, the ventricular septal rupture was anterior, and 75%
      had concomitant coronary artery bypass grafting. Mortality was 39% at 30 days.
      Age was the most important predictor of 30-day and long-term outcome. Logistic
      regression analysis identified age, preoperative ventilation, and female sex as
      significant predictors of 30-day mortality. Cardiogenic shock, preoperative
      ventilation, and advanced age were associated with reduced medium-term survival.
      Surprisingly, anterior ventricular septal rupture was associated with reduced
      long-term survival. Concomitant coronary artery bypass grafting did not influence
      30-day or long-term outcome. CONCLUSIONS: Despite advances, the surgical
      mortality from ventricular septal rupture remains high. Age remains the most
      important predictor of outcome, and concomitant coronary artery bypass grafting
      does not appear to have a demonstrable benefit. Interestingly, anterior
      ventricular septal rupture had poorer long-term outcome than inferior ventricular
      septal rupture.

PMID- 22879547
TI  - A new concept in the sewing rings for mechanical heart valves.
AB  - BACKGROUND: Valve-associated complications challenge the quality of life and
      longevity after heart valve replacement. Inappropriate healing may be a
      contributing factor. OBJECTIVE: To evaluate a new design mechanical heart valve
      in an animal model. METHODS AND RESULTS: The new valve was fabricated by
      substituting the sewing ring with an inbuilt suture ridge and an overlying fabric
      flap. It improved the effective orifice area. Animal experiments were performed
      on pigs to compare this valve with standard valve models. The animals were kept
      on dual antiplatelet drugs. Six of the 8 test animals survived the observation
      period of 140 days compared to 2 of the 6 controls. Among the test valves, one
      had thrombosis and 3 had significant tissue hyperplasia, whereas 5 control valves
      had thrombosis associated with significant tissue hyperplasia. Three test valves
      had paravalvular defects compared to none in the control group. Histology showed
      good tissue incorporation of the fabric flap of the test valves, whereas the
      control valves had tissue infiltration limited to the peripheral fabric layer of
      the sewing ring. CONCLUSION: The new valve has improved effective orifice area,
      and the animal study showed better survival, good healing, and a lower incidence
      of thrombosis and tissue hyperplasia.

PMID- 22879548
TI  - Results of one-hundred and seventy patients after elective Bentall operation.
AB  - The aim of this study was to evaluate the short and long-term operative results
      of patients who underwent a Bentall procedure in a 12-year period. We
      retrospectively analyzed the data of 170 patients who underwent an elective
      Bentall procedure between January 1998 and July 2010. All pre- and perioperative
      variable were entered into a multivariate regression model to identify
      significant predictors of early and late mortality. The early mortality rate was
      11.2% (19/170 patients). Multivariate logistic regression analysis identified
      prior cardiac operation and cardiopulmonary bypass time as independent risk
      factors for early mortality, with odds ratios of 5.75 (95% confidence interval:
      1.850-17.874; p=0.003) and 1.011 (95% confidence interval: 1.003-1.019; p=0.008),
      respectively. The Kaplan-Meier curve shows an overall survival of 78%+/-4% at 5
      years and 66%+/-10% at 10 years. Cox regression analysis revealed no independent
      risk factors for late mortality. The Bentall procedure is still the procedure of
      choice for aortic root replacement. Improvements in perioperative management in
      recent years has improved the early outcome, and in our experience, the late
      results of this technique were satisfactory.

PMID- 22879549
TI  - Detection of ALK fusion in lung cancer using fluorescence in situ hybridization.
AB  - OBJECTIVE: To develop an easy-to-use technique for EML4-ALK detection and
      establish the effective selection of candidates for screening. BACKGROUND: We
      previously reported clinicopathological findings of patients with lung cancer
      harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have
      therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely
      1%-5% of lung cancers. METHODS: We investigated EML4-ALK in tumors from 581
      patients. EML4-ALK was detected by a reverse transcription polymerase-chain
      reaction and by the newly established criteria and algorithm using a fluorescence
      in situ hybridization method. To establish an algorithm to restrict candidates
      chosen for ALK fusion gene detection, clinicopathological findings as well as
      EGFR, ERBB2, and KRAS mutations were analyzed. RESULTS: 8 (1.3%) tumors had EML4
      ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were
      detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We
      screened 581 patients with tumors and another 27 who were nonsmokers or mild
      smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had
      adenocarcinomas exhibiting an acinar component with moderate or poor
      differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK. CONCLUSIONS: We
      propose criteria for selecting candidates for efficient detection of the fusion
      gene.

PMID- 22879550
TI  - Bronchial resection margin and long-term survival in non-small-cell lung cancer.
AB  - Clear resection margins are necessary for long-term survival of patients
      undergoing surgical resection. We aimed to determine whether bronchial resection
      margin is a factor determining long-term survival in patients undergoing R0
      resections for non-small-cell lung cancer. There were 2695 consecutive pulmonary
      resections performed between October 2001 and September 2011 in our institution;
      1795 were R0 resections for non-small-cell lung cancer and bronchial margin
      length data were available. Benchmarking against the 7th International
      Association for the Study of Lung Cancer dataset was performed. Cox multivariate
      and neuronal network analysis was undertaken. Benchmarking failed to reveal any
      significant differences between our data and the 7th International Association
      for the Study of Lung Cancer dataset. Cox regression demonstrated that age
      (p<0.001), sex (p<0.0001), body mass index (p=0.002), T1 stage (p=0.0002), T3
      stage (p<0.0001), N1 stage (p<0.001), forced expiratory volume in 1 s (p<0.0001),
      squamous histology (p=0.009), mixed adenosquamous histology (p=0.008), and
      pneumonectomy (p=0.01) were all significant determinants of long-term survival,
      but bronchial resection margin was not. Neuronal network analysis confirmed these
      findings. Bronchial resection margin length has no impact on long-term survival.

PMID- 22879551
TI  - Postpneumonectomy bronchial stump recurrence and bronchopleural fistula.
AB  - OBJECTIVE: To reduce the incidence of postpneumonectomy local recurrence, and to
      prevent the onset of bronchopleural fistula. BACKGROUND: A long bronchial stump
      with a short tumor-free bronchial margin has been found to be associated with a
      higher incidence of local recurrence, and with the development of bronchopleural
      fistula in some cases. METHODS: 134 patients underwent pneumonectomy for non
      small-cell lung cancer in 2 institutions. Bronchial stump length was measured
      intra-and postoperatively. RESULTS: 30-day postoperative mortality was 2.9%.
      There were 3 postoperative bronchopleural fistulas after right pneumonectomy
      (3/61) and one after left pneumonectomy (1/73; p=0.2; fistula was more frequent
      in the long-stump group), which were successfully treated with carina sutures in
      75% of cases. The overall incidence of local recurrence was strongly related to
      the presence of tumoral microinvasion in the resection margin (100%). CONCLUSION:
      To prevent postpneumonectomy bronchial stump complications, it might be useful to
      use carina closure instead of bronchial closure. Carina closure can reduce local
      recurrence, significantly reduce the fistulization rate, and eliminate the stump
      diverticulum. Reduction of the length of the bronchial stump can be achieved
      using a TA Roticulator linear stapler.

PMID- 22879553
TI  - Stentless bioprosthesis for treatment of traumatic aortic valve rupture.
AB  - Aortic valve rupture after blunt trauma to the chest is an infrequent
      complication that should be considered at the outset in examination of an
      accident victim. The presence of aortic regurgitation with hemodynamic
      instability is an indication for surgery. We implanted a stentless bioprosthesis
      after aortic valve rupture due to chest trauma in a 31-year-old man with
      schizophrenia.

PMID- 22879552
TI  - Prognostic factors in malignant pleural mesothelioma: role of talc pleurodesis.
AB  - OBJECTIVE: To examine baseline characteristics associated with survival in
      patients with malignant pleural mesothelioma. METHODS: 122 patients with
      histologically proven malignant pleural mesothelioma during the period 2000-2010
      were studied. Survival was evaluated by the Kaplan-Meier method with the logrank
      test. Cox regression analysis was used to estimate the hazard ratios for possible
      prognostic factors. RESULTS: 105 (86%) patients had complete survival follow-up;
      91 died and 14 (13.3%) were alive at the end of the observation period starting
      from the day of diagnosis. The median survival was 286 days (95% confidence
      interval: 212-359). Talc pleurodesis was performed in 59 patients, and 17 had
      surgical interventions (2 chest wall resections, 2 extrapleural pneumonectomies,
      and 13 decortications). Chemotherapy was used in 41 patients, port-site radiation
      in 68, and combined therapy in 26. Cox regression analysis identified talc
      pleurodesis (p=0.04), chemotherapy (p<0.001), port-site radiation (p<0.001), and
      combined chemotherapy and port-site radiation (p<0.006) as favorable prognostic
      factors after adjusting for age, sex, histologic subtype, smoking, and
      performance status. CONCLUSIONS: Surgical intervention including decortications
      and extrapleural pneumonectomy had no effect on survival in this series.
      Chemotherapy and radiation to port sites independently and in combination were
      associated with improved overall survival in malignant pleural mesothelioma
      patients. Talc pleurodesis was an independent determinant of survival, but
      further studies are warranted.

PMID- 22879554
TI  - Successful repair of bicuspid aortic valve with two raphae.
AB  - We describe the case of a 17-year-old boy with bicuspid aortic valve with two
      raphae, for whom subvalvular circular annuloplasty and adjustable cusp suspension
      procedures successfully terminated severe regurgitation.

PMID- 22879555
TI  - Interposition of aortic valve leaflets for reinforcement of Bentall proximal
      anastomosis.
AB  - Bleeding from the proximal suture line is not uncommon after composite graft
      anastomosis in the Bentall procedure. The passage of valve sutures through the
      aortic valve leaflets interposed between the pledgets and the cuff of the
      composite valved conduit strengthens the repair.

PMID- 22879556
TI  - Large left atrial thrombus after mitral valve replacement: how to treat?
AB  - An 87-year-old lady, known to have permanent atrial fibrillation, underwent
      tissue mitral valve replacement at our institution. At the two-year follow-up,
      echocardiography revealed a large left atrial thrombus attached to the
      anterolateral wall and the mouth of the left atrial appendage remnant. The
      patient was treated with warfarin. One year later, the mass had fully resolved,
      thus avoiding the need for high-risk redo surgery.

PMID- 22879557
TI  - Teicoplanin-induced neutropenic sepsis mimicking endocarditis.
AB  - Teicoplanin is a less toxic replacement for vancomycin in most situations where
      resistant organisms are encountered, and is therefore the drug of choice. As a
      commonly used drug in cardiac surgery, we treated a case of presumptive
      endocarditis with teicoplanin that caused neutropenic sepsis, unmasked on
      withdrawal of treatment.

PMID- 22879558
TI  - Mesenteric artery fenestration for type B dissection with visceral ischemia.
AB  - We describe a successful case of direct superior mesenteric artery fenestration
      for an acute type B dissection complicated by bowel necrosis in a 68-year-old
      man. At 11 days after the onset, computed tomography showed superior mesenteric
      artery obstruction. We fenestrated and connected the true lumen to the false
      lumen of the superior mesenteric artery, and performed thrombectomy in both
      lumens. A bowel resection was carried out immediately. The patient was discharged
      uneventfully after recovery.

PMID- 22879559
TI  - Acute type A aortic dissection complicated by persistent left superior vena cava.
AB  - Acute type A aortic dissection in a patient with persistent with left superior
      vena cava is a very rare condition. There are some technical problems encountered
      during cardiovascular surgery in such a patient. We describe successful repair of
      acute type A aortic dissection complicated persistent with left superior vena
      cava, and the technical difficulties encountered during surgery.

PMID- 22879560
TI  - Rupture of abdominal aortic aneurysm with shrinkage after endovascular repair.
AB  - An 85-year-old man, who had undergone endovascular abdominal aortic aneurysm
      repair 8&frac12; years earlier, was transferred to the emergency department with
      chest pain and transient loss of consciousness. Computed tomography revealed a
      ruptured abdominal aortic aneurysm with a stent graft inside. His aneurysm was 62
      mm in diameter at the endovascular repair, but 45 mm at the rupture site. He was
      rescued by emergency aneurysmectomy.

PMID- 22879561
TI  - Doehle-Heller aortitis: speed of decision is what saves life.
AB  - A 48-year-old woman presented with severe acute heart failure of 7 days duration.
      Because of her rapidly worsening clinical condition, anatomical diagnosis of
      aortopulmonary fistula was made by urgent cardiac catheterization, and she
      successfully underwent immediate surgical closure. Retrospectively, the diagnosis
      of syphilitic aortitis complicated with aortopulmonary fistula was made by
      clinical profile, serology, and histopathology.

PMID- 22879562
TI  - Biatrial myxomas with Carney complex.
AB  - A 30-year-old man presented with chest pain and was diagnosed with biatrial
      myxomas and pulmonary embolism. He underwent resection of the biatrial myxomas
      and tumor embolectomy from the pulmonary artery. The histological diagnosis was
      multiple cardiac myxomas. Further examination showed that this patient also had
      spotty pigmentations, cutaneous myxomas, and acromegaly. He was diagnosed with
      Carney complex.

PMID- 22879563
TI  - Thymoma hyalinized by steroid therapy in myasthenia gravis.
AB  - We encountered a 72-year-old woman with myasthenia gravis and thymoma who
      received glucocorticoid therapy for respiratory failure before undergoing
      thymectomy. After the antiacetylcholine receptor antibody titer was normalized,
      and the thymoma shrunk with prednisolone, the patient was free from symptoms. On
      pathological examination, the majority of the thymoma (type B2) had been
      hyalinized. Preoperative steroid therapy was effective in stabilizing myasthenia
      gravis and in inducing apoptosis of both epithelial and lymphocytic components of
      the thymoma.

PMID- 22879564
TI  - Successful resection of a huge paraganglioma utilizing cardiopulmonary bypass.
AB  - A 54-year-old woman was diagnosed with a large paraganglioma in the left
      paraaortic area, extending into the aortopulmonary window and up to a right-sided
      superior vena cava. The tumor was treated with repeated embolizations that failed
      to reduce its size. Complete surgical excision was achieved utilizing
      cardiopulmonary bypass. The patient made a full recovery.

PMID- 22879565
TI  - Myasthenia gravis complicated with lung cancer and middle mediastinal thymoma.
AB  - Myasthenia gravis complicated by lung cancer is rare, and the association between
      myasthenia gravis and lung cancer is unclear. Thymoma located in the middle
      mediastinum is very rare. We describe a case of myasthenia gravis complicated
      with lung cancer and middle mediastinal thymoma in a 69-year-old woman.

PMID- 22879566
TI  - Left ventricular assist device thrombosis due to clopidogrel resistance.

PMID- 22879567
TI  - Iatrogenic tracheal tear.

PMID- 22879568
TI  - Angioplasty balloon catheter entrapment.

PMID- 22879569
TI  - Large mass in pericardial cavity: cardiac liposarcoma.

PMID- 22879570
TI  - An alternative method for endoaortic clamping in atherosclerotic aorta.
AB  - To decrease the risk of traumatic injury or dissection of the aorta in patients
      with diffuse atherosclerotic disease or calcification of the ascending aorta, we
      have devised a simple method that uses an Embol-X aortic cannula with a Fogarty
      occlusion catheter.

PMID- 22879571
TI  - Non-sinus rhythm after heart surgery: permanent or not? A simple method can tell.
AB  - We introduce a simple method to distinguish permanent from transient non-sinus
      rhythm immediately after resuscitation in cardiac operations. An ice slush of
      normal saline is sprayed on the surface of the right atrium around the sinus
      node. If the arrhythmia is transient, the heart usually regains sinus rhythm; if
      not, the arrhythmia will most likely be permanent. Although we do not know the
      mechanism, this technique is easy and has worked well in 162 patients.

PMID- 22879572
TI  - Cross-cultural adaption and measurement properties of the Danish version of the
      Shoulder Pain and Disability Index.
AB  - OBJECTIVE: To cross-culturally adapt the Danish version of the Shoulder Pain and
      Disability Index and to evaluate its measurement properties in terms of
      reliability and known-group validity. DESIGN: Test-retest study. SETTING:
      Outpatient Clinic of the Department of Orthopaedic Surgery, Regional Hospital
      Herning, Denmark. SUBJECTS: Consecutive shoulder patients referred to an
      outpatient clinic. METHODS: The Shoulder Pain and Disability Index was translated
      from English into Danish according to international guidelines. The questionnaire
      was posted to patients one to two weeks before their scheduled clinical
      examination and repeated on the day of the examination. RESULTS: A total of 65
      patients with a variety of shoulder diagnoses were included in the study. No
      significant differences were found in scores between the first and the second
      questionnaire. The minimal detectable change was estimated to 19.4 points, and
      the intraclass correlation coefficient was 0.88 (95% confidence interval 0.83 to
      0.94). Internal consistency measured by Cronbach's alpha was 0.94. The
      questionnaire was found to discriminate well between currently working and non
      working patients. CONCLUSION: The Shoulder Pain and Disability Index provides a
      sensitive and reliable tool to assess pain and disability in Danish-speaking
      orthopaedic shoulder patients.

PMID- 22879573
TI  - Stopping a trial early - and then what?
AB  - BACKGROUND: This article addresses a problem arising when a trial shows such
      strong evidence of benefit of the tested intervention that it stops early with an
      observed effect size for the experimental treatment that is statistically
      significantly better than the control. Within the classical frequentist framework
      of group sequential trials, the observed estimated effect size, the associated
      naive confidence interval, and the p-value are all biased estimates of the true
      values. The bias is in the direction of the overestimation of the treatment
      effect, creation of narrower confidence intervals than appropriate, and a p-value
      that is too small. PURPOSE: To discuss methods for correcting the bias in
      observed effect sizes, confidence intervals, and p-values for trials stopped
      early and to show the extent to which such correction would have modified the
      conclusions of the Randomized Aldactone Evaluation Study (RALES). RESULTS: In
      RALES, the effect of not correcting for bias is negligible. LIMITATIONS: This
      article does not show general results; it only explores a few examples that use
      conservative methods for early stopping. It does not consider sequential methods
      that allow a relatively high probability of stopping early. CONCLUSIONS: This
      article points out that there is no unique solution to the correction of the p
      value, but it recommends stagewise ordering, which states that earlier stopping
      of a trial is ipso facto stronger evidence of effect than later stopping so long
      as the stopping is governed by a monitoring boundary that preserves the Type I
      error rate. Associated with stagewise ordering is a method for calculating the
      estimated effect size and its confidence interval. In the RALES trial, which
      stopped at 50% information time, the corrections to the estimated values are
      small.

PMID- 22879575
TI  - The issue of multiplicity in noninferiority studies.
AB  - BACKGROUND: In a clinical study to evaluate noninferiority (NI) of an
      experimental drug relative to an established therapy, it is common to further
      test superiority of the experimental drug after NI is established. It has been
      shown that no multiplicity issue exists between NI and superiority tests of the
      primary endpoint. However, when there is an additional, or secondary, endpoint
      that will be tested for superiority in a hierarchical fashion to the NI testing
      of the primary endpoint, it is not clear whether the overall type I error rate is
      strictly controlled among all the tests. PURPOSE: In this article, our goal is to
      evaluate if the family-wise type I error rate is strictly controlled in this
      setting. We also evaluate a multiplicity adjustment procedure based on the
      Hochberg procedure. METHODS: We use the closed testing principle to evaluate the
      family-wise type I error rate. Some simulations are performed to appreciate the
      magnitude of the potential inflation of the type I error rate. RESULTS: It is
      demonstrated that the family-wise type I error rate is not controlled and an
      appropriate multiplicity adjustment procedure must take into account the NI and
      superiority tests of the two endpoints. When the test statistic used for
      superiority testing of the primary endpoint is the same as that for the NI
      testing, a multiplicity adjustment method using the popular Hochberg procedure is
      shown to be potentially conservative. LIMITATION: The assessment is based on a
      simplified set-up where there is only one secondary endpoint tested for
      superiority in addition to the primary endpoint. CONCLUSION: It is necessary to
      evaluate the issue of multiplicity in non-inferiority studies to assure strict
      control of the family-wise type I error rate.

PMID- 22879574
TI  - Addressing methodological challenges in implementing the nursing home pain
      management algorithm randomized controlled trial.
AB  - BACKGROUND: Unrelieved pain among nursing home (NH) residents is a well
      documented problem. Attempts have been made to enhance pain management for older
      adults, including those in NHs. Several evidence-based clinical guidelines have
      been published to assist providers in assessing and managing acute and chronic
      pain in older adults. Despite the proliferation and dissemination of these
      practice guidelines, research has shown that intensive systems-level
      implementation strategies are necessary to change clinical practice and patient
      outcomes within a health-care setting. One promising approach is the embedding of
      guidelines into explicit protocols and algorithms to enhance decision making.
      PURPOSE: The goal of the article is to describe several issues that arose in the
      design and conduct of a study that compared the effectiveness of pain management
      algorithms coupled with a comprehensive adoption program versus the effectiveness
      of education alone in improving evidence-based pain assessment and management
      practices, decreasing pain and depressive symptoms, and enhancing mobility among
      NH residents. METHODS: The study used a cluster-randomized controlled trial (RCT)
      design in which the individual NH was the unit of randomization. The Roger's
      Diffusion of Innovations theory provided the framework for the intervention.
      Outcome measures were surrogate-reported usual pain, self-reported usual and
      worst pain, and self-reported pain-related interference with activities,
      depression, and mobility. RESULTS: The final sample consisted of 485 NH residents
      from 27 NHs. The investigators were able to use a staggered enrollment strategy
      to recruit and retain facilities. The adaptive randomization procedures were
      successful in balancing intervention and control sites on key NH characteristics.
      Several strategies were successfully implemented to enhance the adoption of the
      algorithm. LIMITATIONS/LESSONS: The investigators encountered several
      methodological challenges that were inherent to both the design and
      implementation of the study. The most problematic issue concerned the measurement
      of outcomes in persons with moderate to severe cognitive impairment. It was
      difficult to identify valid, reliable, and sensitive outcome measures that could
      be applied to all NH residents regardless of the ability to self-report. Another
      challenge was the inability to incorporate advances in implementation science
      into the ongoing study CONCLUSIONS: Methodological challenges are inevitable in
      the conduct of an RCT. The need to optimize internal validity by adhering to the
      study protocol is compromised by the emergent logistical issues that arise during
      the course of the study.

PMID- 22879576
TI  - Cancer-specific concerns and physical activity among recently diagnosed breast
      and prostate cancer survivors.
AB  - BACKGROUND: Cancer treatment -related side effects may have a negative impact on
      quality of life among cancer survivors and may limit participation in physical
      activity (PA). HYPOTHESIS: Cancer-specific concerns will be reduced throughout a
      10-month diet and exercise intervention among recently diagnosed cancer
      survivors. Additionally, participants reporting greater levels of PA will also
      report fewer cancer-specific concerns. STUDY DESIGN: This study is an exploratory
      analysis of 452 recently diagnosed, early-stage breast and prostate cancer
      survivors who participated in the FRESH START diet and exercise trial. Data were
      collected at baseline and 1-year follow-up. RESULTS: At baseline, chief concerns
      among prostate cancer survivors included ability to have an erection (mean score
      [standard deviation] = 1.0 [1.3]) and urinary frequency (2.5 [1.4]), whereas
      among breast cancer survivors, eminent concerns were not feeling sexually
      attractive (2.0 [1.3]) and worry about cancer in other members of their family
      (2.1 [1.3]). At 1 year, there was a significant improvement in cancer-specific
      concerns on breast cancer-specific concerns (P < .01) but not on prostate cancer
      specific concerns. At baseline, women who were self-conscious about their dress
      had higher levels of PA, whereas men reporting issues with incontinence reported
      lesser increases in PA in response to the intervention. CONCLUSION: Cancer
      specific concerns diminish over time, especially among breast cancer survivors.
      Among prostate cancer survivors, incontinence is a significant barrier that
      hinders benefit from PA interventions. Thus, there is a need either for medical
      interventions to ameliorate incontinence or for behavioral interventions to
      address this issue among survivors.

PMID- 22879577
TI  - A pilot study of the efficacy of a computerized executive functioning remediation
      training with game elements for children with ADHD in an outpatient setting:
      outcome on parent- and teacher-rated executive functioning and ADHD behavior.
AB  - OBJECTIVE: This pilot study tested the short- and long-term efficacy (9 weeks
      follow-up) of an executive functioning (EF) remediation training with game
      elements for children with ADHD in an outpatient clinical setting, using a
      randomized controlled wait-list design. Furthermore, in a subsample, that is,
      those treated with methylphenidate, additive effects of the EF training were
      assessed. METHOD: A total of 40 children (aged 8-12 years) were randomized to the
      EF training or wait-list. The training consisted of a 25-session training of
      inhibition, cognitive flexibility, and working memory. Treatment outcome was
      assessed by parent- and teacher-rated EF, ADHD, oppositional deviant disorder,
      and conduct disorder symptoms. RESULTS: Children in the EF training showed
      significantly more improvement than those in the wait-list condition on parent
      rated EF and ADHD behavior in the total sample and in the subsample treated with
      methylphenidate. Effects were maintained at follow-up. CONCLUSION: This pilot
      study shows promising evidence for the efficacy of an EF training with game
      elements.

PMID- 22879579
TI  - Effects of red light-emitting diode irradiation on dental pulp cells.
AB  - Light irradiation activates a range of cellular processes in a variety of cell
      types, including stem cells, and can promote tissue repair. This study
      investigated the effects of light-emitting diode (LED) exposure on dental pulp
      cells (DPCs). Dose response analysis at 20-second intervals up to 120 seconds
      demonstrated that a LED array emitting 653-nm red light stimulated significantly
      increased cell growth at 3 and 7 days post-irradiation with 40 (149 mJ/cm(2)) and
      60 (224 mJ/cm(2)) seconds of radiant exposure. Double-dosing cells at days 1 and
      4 of a 7-day culture period with 60-second (224 mJ/cm(2)) LED exposure
      significantly increased cell growth compared with a single dosing regime. BrdU
      analysis demonstrated significantly increased proliferation rates associated with
      significantly increased ATP, nitric oxide (NO), and mitochondrial metabolic
      activity. LED-stimulated NO levels were not reduced by inhibition of NO-synthase
      activity. Light exposure also rescued the inhibition of mitochondrial dysfunction
      and increased levels of in vitro mineralization compared with control. Media
      exchange experiments indicated that autocrine signaling was not likely
      responsible for red-light-induced DPC activity. In conclusion, data analysis
      indicated that 653-nm LED irradiation promoted DPC responses relevant to tissue
      repair, and this is likely mediated by increased mitochondrial activity.

PMID- 22879578
TI  - MicroRNAs and their target genes in gingival tissues.
AB  - To gain insights into the in vivo function of miRNAs in the context of
      periodontitis, we examined the occurrence of miRNAs in healthy and diseased
      gingival tissues and validated their in silico-predicted targets through mRNA
      profiling using whole-genome microarrays in the same specimens. Eighty-six
      individuals with periodontitis contributed 198 gingival papillae: 158 'diseased'
      (bleeding-on-probing, PD > 4 mm, and AL >= 3 mm) and 40 'healthy' (no bleeding,
      PD <= 4 mm, and AL <= 2 mm). Expression of 1,205 miRNAs was assessed by
      microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted
      miRNA targets were identified and tested for enrichment by Gene Set Enrichment
      Analysis (GSEA). Enriched gene sets were grouped in functional categories by
      DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were
      significantly differentially expressed between healthy and diseased gingiva. Four
      miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were
      significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa
      miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2
      fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60
      enriched miRNA gene sets with target genes involved in immune/inflammatory
      responses and tissue homeostasis. This is the first study that concurrently
      examined miRNA and mRNA expression in gingival tissues and will inform
      mechanistic experimentation to dissect the role of miRNAs in periodontal tissue
      homeostasis and pathology.

PMID- 22879580
TI  - Role of thromboxane receptor in C-reactive protein-induced thrombosis.
AB  - OBJECTIVE: Thromboxane A(2) and prostacyclin are thromboregulatory
      prostaglandins. The inflammatory C-reactive protein (CRP) promotes thrombosis
      after vascular injury, presumably via potentiation of thromboxane activity. Using
      a genetic approach, we investigated the role of thromboxane receptor (TP) pathway
      in CRP-induced thrombosis. METHODS AND RESULTS: Four genetically engineered mice
      strains were used: C57BL/6 wild-type, human CRP transgenic (CRPtg), thromboxane
      receptor-deficient (Tp(-/-)), and CRPtgTp(-/-) mice. CRP and TP expression were
      correlated, and suppression of CRP expression using small interfering RNA/CRP led
      to reduction in TP expression. Platelet-endothelial adherence was increased in
      CRPtg and suppressed in CRPtgTP(-/-)and CRPtg cells that were suppressed with TP
      small interfering RNA. TP deficiency in both platelets and endothelial cells was
      synergistic in affecting platelet-endothelial interactions. Time until arterial
      occlusion, measured after photochemical injury, was significantly shorter in
      CRPtg and prolonged in CRPtgTp(-/-) compared with controls (n=10-15, 35+/-3.4,
      136+/-13.8, and 67+/-8.9 minutes, respectively; P<0.05). CONCLUSIONS: TP pathway
      is of major importance in CRP-induced thrombosis. The expression of TP is
      increased in CRPtg endothelial cells, and its blockade significantly suppresses
      the prothrombotic effect of CRP.

PMID- 22879581
TI  - Nanoparticle-mediated delivery of pioglitazone enhances therapeutic
      neovascularization in a murine model of hindlimb ischemia.
AB  - OBJECTIVE: Critical limb ischemia is a severe form of peripheral artery disease
      (PAD) for which neither surgical revascularization nor endovascular therapy nor
      current medicinal therapy has sufficient therapeutic effects. Peroxisome
      proliferator activated receptor-gamma agonists present angiogenic activity in
      vitro; however, systemic administration of peroxisome proliferator-activated
      receptor-gamma agonists is hampered by its side effects, including heart failure.
      Here, we demonstrate that the nanoparticle (NP)-mediated delivery of the
      peroxisome proliferator activated receptor-gamma agonist pioglitazone enhances
      its therapeutic efficacy on ischemia-induced neovascularization in a murine
      model. METHODS AND RESULTS: In a nondiabetic murine model of hindlimb ischemia, a
      single intramuscular injection of pioglitazone-incorporated NP (1 ug/kg) into
      ischemic muscles significantly improved the blood flow recovery in the ischemic
      limbs, significantly increasing the number of CD31-positive capillaries and alpha
      smooth muscle actin-positive arterioles. The therapeutic effects of pioglitazone
      incorporated NP were diminished by the peroxisome proliferator activated receptor
      gamma antagonist GW9662 and were not observed in endothelial NO synthase
      deficient mice. Pioglitazone-incorporated NP induced endothelial NO synthase
      phosphorylation, as demonstrated by Western blot analysis, as well as expression
      of multiple angiogenic growth factors in vivo, including vascular endothelial
      growth factor-A, vascular endothelial growth factor-B, and fibroblast growth
      factor-1, as demonstrated by real-time polymerase chain reaction. Intramuscular
      injection of pioglitazone (1 ug/kg) was ineffective, and oral administration
      necessitated a >500 MUg/kg per day dose to produce therapeutic effects equivalent
      to those of pioglitazone-incorporated NP. CONCLUSIONS: NP-mediated drug delivery
      is a novel modality that may enhance the effectiveness of therapeutic
      neovascularization, surpassing the effectiveness of current treatments for
      peripheral artery disease with critical limb ischemia.

PMID- 22879583
TI  - Visualization of vascular inflammation in the atherosclerotic mouse by ultrasmall
      superparamagnetic iron oxide vascular cell adhesion molecule-1-specific
      nanoparticles.
AB  - OBJECTIVE: Noninvasive imaging of atherosclerosis remains challenging in clinical
      applications. Here, we applied noninvasive molecular imaging to detect vascular
      cell adhesion molecule-1 in early and advanced atherosclerotic lesions of
      apolipoprotein E-deficient mice. METHODS AND RESULTS: Ultrasmall
      superparamagnetic iron oxide particles functionalized with (P03011) or without
      (P3007) vascular cell adhesion molecule-1-binding peptide were visualized by
      ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a
      marked signal loss in the aortic root of apolipoprotein E-deficient mice fed a
      Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection
      measurements, P3007-injected mice, and P03011- or P3007-injected age-matched
      C57BL/6 controls. Histological analyses revealed iron accumulations in the
      intima, in colocalization with vascular cell adhesion molecule-1-expressing
      macrophages and endothelial cells. Coherent anti-Stokes Raman scattering
      microscopy demonstrated iron signals in the intima and media of the aortic root
      in the P03011-injected but not untreated apolipoprotein E-deficient mice,
      localized to macrophages, luminal endothelial-like cells, and medial regions
      containing smooth muscle cells. Electron microscopy confirmed iron particles
      enclosed in endothelial cells and in the vicinity of smooth muscle cells.
      CONCLUSIONS: Using a combination of innovative imaging modalities, in this study,
      we demonstrate the feasibility of applying P03011 as a contrast agent for imaging
      of atherosclerosis.

PMID- 22879582
TI  - Adverse alterations in mitochondrial function contribute to type 2 diabetes
      mellitus-related endothelial dysfunction in humans.
AB  - OBJECTIVE: Mitochondrial dysfunction plays a key pathophysiological role in type
      2 diabetes mellitus (T2DM). Data delineating relationships between mitochondrial
      and endothelial dysfunction in humans with T2DM are lacking. METHODS AND RESULTS:
      In 122 human subjects (60 with T2DM, 62 without T2DM), we measured endothelial
      function by brachial artery ultrasound (flow mediated dilation) and digital pulse
      amplitude tonometery. Endothelial function in arterioles isolated from gluteal
      subcutaneous adipose was measured by videomicroscopy. In arterioles and
      mononuclear cells, we measured inner mitochondrial membrane potential
      (Deltapsi(m)), mitochondrial mass, and mitochondrial superoxide production using
      fluorophores. Endothelial function was impaired in T2DM subjects versus control
      subjects. Deltapsi(m) magnitude was larger and mitochondrial mass was lower in
      arterioles and mononuclear cells in T2DM. Mononuclear mitochondrial mass
      correlated with flow-mediated dilation and pulse amplitude tonometery (rho=0.38
      and 0.33, P=0.001 and 0.02, respectively), and mononuclear mitochondrial
      superoxide production inversely correlated with flow-mediated dilation (rho=
      0.58, P=0.03). Low doses of 2 different mitochondrial uncoupling agents (carbonyl
      cyanide m-chlorophenyl hydrazone and 2,4-dinitrophenol) that reduce Deltapsi(m)
      magnitude and a mitochondrial-targeted antioxidant (MitoTEMPOL) improved
      endothelial function and reduced mitochondrial superoxide levels in T2DM
      arterioles. CONCLUSIONS: Mitochondrial dysfunction may play a central role in the
      impairment of endothelial dysfunction in T2DM.

PMID- 22879584
TI  - Elevated protein kinase C-delta contributes to aneurysm pathogenesis through
      stimulation of apoptosis and inflammatory signaling.
AB  - OBJECTIVE: Apoptosis of smooth muscle cells (SMCs) is a prominent pathological
      characteristic of abdominal aortic aneurysm (AAA). We have previously shown that
      SMC apoptosis stimulates proinflammatory signaling in a mouse model of AAA. Here,
      we test whether protein kinase C-delta (PKCdelta), an apoptotic mediator,
      participates in the pathogenesis of AAA by regulating apoptosis and
      proinflammatory signals. METHODS AND RESULTS: Mouse experimental AAA is induced
      by perivascular administration of CaCl(2). Mice deficient in PKCdelta exhibit a
      profound reduction in aneurysmal expansion, SMC apoptosis, and transmural
      inflammation as compared with wild-type littermates. Delivery of PKCdelta to the
      aortic wall of PKCdelta(-/-) mice restores aneurysm, whereas overexpression of a
      dominant negative PKCdelta mutant in the aorta of wild-type mice attenuates
      aneurysm. In vitro, PKCdelta(-/-) aortic SMCs exhibit significantly impaired
      monocyte chemoattractant protein-1 production. Ectopic administration of
      recombinant monocyte chemoattractant protein-1 to the arterial wall of PKCdelta(
      /-) mice restores inflammatory response and aneurysm development. CONCLUSIONS:
      PKCdelta is an important signaling mediator for SMC apoptosis and inflammation in
      a mouse model of AAA. By stimulating monocyte chemoattractant protein-1
      expression in aortic SMCs, upregulated PKCdelta exacerbates the inflammatory
      process, in turn perpetuating elastin degradation and aneurysmal dilatation.
      Inhibition of PKCdelta may serve as a potential therapeutic strategy for AAA.

PMID- 22879585
TI  - Increased epidermal growth factor-like ligands are associated with elevated
      vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model
      of atherosclerosis.
AB  - OBJECTIVE: To characterize the relationship between the expression of epidermal
      growth factor (EGF)-like ligands and vascular nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase expression and activity in a primate model of
      atherosclerosis. METHODS AND RESULTS: Adult male Cynomolgus monkeys were fed a
      normal or atherogenic (AS) diet for 45 months, after which animals from the AS
      group were placed on a normal diet for 8 months (regression). The expression of
      membrane-associated EGF-like ligands was increased in arteries from animals on
      the AS diet and normalized in the regression group. EGF-like ligands were
      distributed throughout atherosclerotic vessels but predominantly colocalized with
      macrophages. Consistent with ligand shedding, circulating heparin-bound EGF was
      elevated in the plasma of AS monkeys but not in those on regression diet.
      Atherosclerosis was associated with the activation of EGF receptor signaling.
      Expression of NADPH oxidase subunits Nox1 and Nox2 but not Nox4 or Nox5 was
      increased in arteries from monkeys on the AS diet and returned to normal with
      regression. Levels of Nox1 and Nox2 positively correlated with EGF-like ligands.
      In cultured monkey smooth muscle cells, treatment with EGF-like ligands increased
      Nox1 expression and activity. CONCLUSIONS: These data identify EGF-like ligands
      as potential modulators of atherogenesis, resulting in part from increased
      vascular NADPH oxidase activity.

PMID- 22879586
TI  - Cell surface expression of human ether-a-go-go-related gene (hERG) channels is
      regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2.
AB  - The human ether-a-go-go-related gene (hERG) encodes the rapidly activating
      delayed rectifier potassium channel (I(Kr)) which plays an important role in
      cardiac repolarization. A reduction or increase in hERG current can cause long or
      short QT syndrome, respectively, leading to fatal cardiac arrhythmias. The
      channel density in the plasma membrane is a key determinant of the whole cell
      current amplitude. To gain insight into the molecular mechanisms for the
      regulation of hERG density at the plasma membrane, we used whole cell voltage
      clamp, Western blotting, and immunocytochemical methods to investigate the
      effects of an integral membrane protein, caveolin-3 (Cav3) on hERG expression
      levels. Our data demonstrate that Cav3, hERG, and ubiquitin-ligase Nedd4-2
      interact with each other and form a complex. Expression of Cav3 thus enhances the
      hERG-Nedd4-2 interaction, leading to an increased ubiquitination and degradation
      of mature, plasma-membrane localized hERG channels. Disrupting Nedd4-2
      interaction with hERG by mutations eliminates the effects of Cav3 on hERG
      channels. Knockdown of endogenous Cav3 or Nedd4-2 in cultured neonatal rat
      ventricular myocytes using siRNA led to an increase in native I(Kr). Our data
      demonstrate that hERG expression in the plasma membrane is regulated by Cav3 via
      Nedd4-2. These findings extend our understanding of the regulation of hERG
      channels and cardiac electrophysiology.

PMID- 22879587
TI  - Annexin A2 and A5 serve as new ligands for C1q on apoptotic cells.
AB  - C1q is the initiator of the classical complement pathway and opsonizes apoptotic
      cells to facilitate phagocytosis. Deficiency of C1q is the strongest known risk
      factor for development of systemic lupus erythematosus (SLE), which appears to be
      related to ensuing impaired clearance of apoptotic material. The objective of the
      current study was to investigate new ligands for C1q on the surface of apoptotic
      cells. We revealed that the two phospholipid-binding proteins annexin A2 and A5
      are, beside DNA, significant C1q ligands. We furthermore, demonstrated that C1q
      binds directly to histones exposed on the surface of dying cells but we did not
      detect significant interaction with phosphatidylserine. The complement inhibitors
      C4b-binding protein and factor H also interact with dying cells, most likely to
      decrease complement activation beyond the level of C3 to allow noninflammatory
      clearance. Despite the fact that C4b-binding protein, factor H, and C1q share
      some ligands on dying cells, we showed that these three proteins did not compete
      with one another for binding to apoptotic cells. We additionally demonstrated
      that the way in which apoptosis is induced influenced both the degree of
      apoptosis and the binding of C1q. The knowledge, that annexin A2 and A5 act as
      ligands for C1q on apoptotic cells, sheds new light on the pathophysiology of
      autoimmune diseases.

PMID- 22879588
TI  - The biology of small leucine-rich proteoglycans in bone pathophysiology.
AB  - The class of small leucine-rich proteoglycans (SLRPs) is a family of homologous
      proteoglycans harboring relatively small (36-42 kDa) protein cores compared with
      the larger cartilage and mesenchymal proteoglycans. SLRPs have been localized to
      most skeletal regions, with specific roles designated during all phases of bone
      formation, including periods relating to cell proliferation, organic matrix
      deposition, remodeling, and mineral deposition. This is mediated by key signaling
      pathways regulating the osteogenic program, including the activities of TGF-beta,
      bone morphogenetic protein, Wnt, and NF-kappaB, which influence both the number
      of available osteogenic precursors and their subsequent development,
      differentiation, and function. On the other hand, SLRP depletion is correlated
      with degenerative diseases such as osteoporosis and ectopic bone formation. This
      minireview will focus on the SLRP roles in bone physiology and pathology.

PMID- 22879590
TI  - Transfer-messenger RNA-SmpB protein regulates ribonuclease R turnover by
      promoting binding of HslUV and Lon proteases.
AB  - RNase R, an important exoribonuclease involved in degradation of structured RNA,
      is subject to a novel mechanism of regulation. The enzyme is extremely unstable
      in rapidly growing cells but becomes stabilized under conditions of stress, such
      as stationary phase or cold shock. RNase R instability results from acetylation
      which promotes binding of tmRNA-SmpB, two trans-translation factors, to its C
      terminal region. Here, we examine how binding of tmRNA-SmpB leads to proteolysis
      of RNase R. We show that RNase R degradation is due to two proteases, HslUV and
      Lon. In their absence, RNase R is stable. We also show, using an in vitro system
      that accurately replicates the in vivo process, that tmRNA-SmpB is not essential,
      but it stimulates binding of the protease to the N-terminal region of RNase R and
      that it does so by a direct interaction between the protease and SmpB which
      stabilizes protease binding. Thus, a sequence of events, initiated by acetylation
      of a single Lys residue, results in proteolysis of RNase R in exponential phase
      cells. RNase R in stationary phase or in cold-shocked cells is not acetylated,
      and thereby remains stable. Such a regulatory mechanism, dependent on protein
      acetylation, has not been observed previously in bacterial cells.

PMID- 22879589
TI  - Evidence for bidirectional endocannabinoid transport across cell membranes.
AB  - Despite extensive research on the trafficking of anandamide (AEA) across cell
      membranes, little is known about the membrane transport of other
      endocannabinoids, such as 2-arachidonoylglycerol (2-AG). Previous studies have
      provided data both in favor and against a cell membrane carrier-mediated
      transport of endocannabinoids, using different methodological approaches. Because
      AEA and 2-AG undergo rapid and almost complete intracellular hydrolysis, we
      employed a combination of radioligand assays and absolute quantification of
      cellular and extracellular endocannabinoid levels. In human U937 leukemia cells,
      100 nm AEA and 1 MUm 2-AG were taken up through a fast and saturable process,
      reaching a plateau after 5 min. Employing differential pharmacological blockage
      of endocannabinoid uptake, breakdown, and interaction with intracellular binding
      proteins, we show that eicosanoid endocannabinoids harboring an arachidonoyl
      chain compete for a common membrane target that regulates their transport,
      whereas other N-acylethanolamines did not interfere with AEA and 2-AG uptake. By
      combining fatty acid amide hydrolase or monoacyl glycerol lipase inhibitors with
      hydrolase-inactive concentrations of the AEA transport inhibitors UCM707 (1 MUm)
      and OMDM-2 (5 MUm), a functional synergism on cellular AEA and 2-AG uptake was
      observed. Intriguingly, structurally unrelated AEA uptake inhibitors also blocked
      the cellular release of AEA and 2-AG. We show, for the first time, that UCM707
      and OMDM-2 inhibit the bidirectional movement of AEA and 2-AG across cell
      membranes. Our findings suggest that a putative endocannabinoid cell membrane
      transporter controls the cellular AEA and 2-AG trafficking and metabolism.

PMID- 22879591
TI  - Cathepsin G-regulated release of formyl peptide receptor agonists modulate
      neutrophil effector functions.
AB  - Neutrophil serine proteases play an important role in inflammation by modulating
      neutrophil effector functions. We have previously shown that neutrophils
      deficient in the serine proteases cathepsin G and neutrophil elastase (CG/NE
      neutrophils) exhibit severe defects in chemokine CXCL2 release and reactive
      oxygen species (ROS) production when activated on immobilized immune complex.
      Exogenously added active CG rescues these defects, but the mechanism remains
      undefined. Using a protease-based proteomic approach, we found that, in vitro,
      the addition of exogenous CG to immune complex-stimulated CG/NE neutrophils led
      to a decrease in the level of cell-associated annexin A1 (AnxA1) and cathelin
      related antimicrobial peptide (CRAMP), both known inflammatory mediators. We
      further confirmed that, in vivo, CG was required for the extracellular release of
      AnxA1 and CRAMP in a subcutaneous air pouch model. In vitro, CG efficiently
      cleaved AnxA1, releasing the active N-terminal peptide Ac2-26, and processed
      CRAMP in limited fashion. Ac2-26 and CRAMP peptides enhanced the release of CXCL2
      by CG/NE neutrophils in a dose-dependent manner via formyl peptide receptor (FPR)
      stimulation. Blockade of FPRs by an antagonist, Boc2 (t-Boc-Phe-d-Leu-Phe-d-Leu
      Phe), abrogates CXCL2 release, whereas addition of FPR agonists, fMLF and F2L,
      relieves Boc2 inhibition. Furthermore, the addition of active CG, but not
      inactive CG, also relieves Boc2 inhibition. These findings suggest that CG
      modulates neutrophil effector functions partly by controlling the release (and
      proteolysis) of FPR agonists. Unexpectedly, we found that mature CRAMP, but not
      Ac2-26, induced ROS production through an FPR-independent pathway.

PMID- 22879592
TI  - Mutations to the formin homology 2 domain of INF2 protein have unexpected effects
      on actin polymerization and severing.
AB  - INF2 (inverted formin 2) is a formin protein with unusual biochemical
      characteristics. As with other formins, the formin homology 2 (FH2) domain of
      INF2 accelerates actin filament assembly and remains at the barbed end,
      modulating elongation. The unique feature of INF2 is its ability to sever
      filaments and enhance depolymerization, which requires the C-terminal region.
      Physiologically, INF2 acts in the secretory pathway and is mutated in two human
      diseases, focal and segmental glomerulosclerosis and Charcot-Marie-Tooth disease.
      In this study, we investigate the effects of mutating two FH2 residues found to
      be key in other formins: Ile-643 and Lys-792. Surprisingly, neither mutation
      abolishes barbed end binding, as judged by pyrene-actin and total internal
      reflection (TIRF) microscopy elongation assays. The I643A mutation causes tight
      capping of a subset of filaments, whereas K792A causes slow elongation of all
      filaments. The I643A mutation has a minor inhibitory effect on polymerization
      activity but causes almost complete abolition of severing and depolymerization
      activity. The K792A mutation has relatively small effects on polymerization,
      severing, and depolymerization. In cells, the K792A mutant causes actin
      accumulation around the endoplasmic reticulum to a similar extent as wild type,
      whereas the I643A mutant causes no measurable polymerization. The inability of
      I643A to induce actin polymerization in cells is explained by its inability to
      promote robust actin polymerization in the presence of capping protein. These
      results highlight an important point: it is dangerous to assume that mutation of
      conserved FH2 residues will have equivalent effects in all formins. The work also
      suggests that both mutations have effects on the mechanism of processive
      elongation.

PMID- 22879593
TI  - Large protein assemblies formed by multivalent interactions between cadherin23
      and harmonin suggest a stable anchorage structure at the tip link of stereocilia.
AB  - Stereocilia tip links of inner ear hair cells are subjected to constant
      stretching during hair-bundle deflection, and accordingly are well designed to
      prevent from being broken by mechanical tensions. The roots of tip links, which
      couple tip links with the cytoskeleton, supposedly play important roles in
      withstanding large forces under stimulated conditions. The upper root of the tip
      link is mainly formed by the cytoplasmic tail of cadherin23 and its actin
      anchoring protein harmonin. However, the detailed organization mode of the two
      proteins that gives rise to a strong upper root remains unclear. Here we show
      that the exon68-encoded peptide of cadherin23 can either interact with the N
      terminal domain (NTD) of harmonin or form a homodimer. We demonstrate that the
      three harmonin binding sites of cadherin23, namely the NTD-binding motif, the
      exon68 peptide, and the C-terminal PDZ binding motif, do not synergize with each
      other in binding to harmonin, instead they facilitate formation of polymeric
      cadherin23/harmonin complexes. The exon68 peptide can promote the
      cadherin23/harmonin polymer formation via either binding to harmonin NTD or self
      dimerization. We propose that the polymeric cadherin23/harmonin complex formed
      beneath the upper tip link membranes may serve as part of the stable rootlet
      structure for anchoring the tip links of stereocilia.

PMID- 22879594
TI  - Positive regulation by gamma-aminobutyric acid B receptor subunit-1 of
      chondrogenesis through acceleration of nuclear translocation of activating
      transcription factor-4.
AB  - A view that signaling machineries for the neurotransmitter gamma-aminobutyric
      acid (GABA) are functionally expressed by cells outside the central nervous
      system is now prevailing. In this study, we attempted to demonstrate functional
      expression of GABAergic signaling molecules by chondrocytes. In cultured murine
      costal chondrocytes, mRNA was constitutively expressed for metabotropic GABA(B)
      receptor subunit-1 (GABA(B)R1), but not for GABA(B)R2. Immunohistochemical
      analysis revealed the predominant expression of GABA(B)R1 by prehypertrophic to
      hypertrophic chondrocytes in tibial sections of newborn mice. The GABA(B)R
      agonist baclofen failed to significantly affect chondrocytic differentiation
      determined by Alcian blue staining and alkaline phosphatase activity in cultured
      chondrocytes, whereas newborn mice knocked out of GABA(B)R1 (KO) showed a
      decreased body size and delayed calcification in hyoid bone and forelimb and
      hindlimb digits. Delayed calcification was also seen in cultured metatarsals from
      KO mice with a marked reduction of Indian hedgehog gene (Ihh) expression.
      Introduction of GABA(B)R1 led to synergistic promotion of the transcriptional
      activity of activating transcription factor-4 (ATF4) essential for normal
      chondrogenesis, in addition to facilitating ATF4-dependent Ihh promoter
      activation. Although immunoreactive ATF4 was negligibly detected in the nucleus
      of chondrocytes from KO mice, ATF4 expression was again seen in the nucleus and
      cytoplasm after the retroviral introduction of GABA(B)R1 into cultured
      chondrocytes from KO mice. In nuclear extracts of KO chondrocytes, a marked
      decrease was seen in ATF4 DNA binding. These results suggest that GABA(B)R1
      positively regulates chondrogenesis through a mechanism relevant to the
      acceleration of nuclear translocation of ATF4 for Ihh expression in chondrocytes.

PMID- 22879595
TI  - Unraveling the role of the C-terminal helix turn helix of the coat-binding domain
      of bacteriophage P22 scaffolding protein.
AB  - Many viruses encode scaffolding and coat proteins that co-assemble to form
      procapsids, which are transient precursor structures leading to progeny virions.
      In bacteriophage P22, the association of scaffolding and coat proteins is
      mediated mainly by ionic interactions. The coat protein-binding domain of
      scaffolding protein is a helix turn helix structure near the C terminus with a
      high number of charged surface residues. Residues Arg-293 and Lys-296 are
      particularly important for coat protein binding. The two helices contact each
      other through hydrophobic side chains. In this study, substitution of the
      residues of the interface between the helices, and the residues in the beta-turn,
      by aspartic acid was used examine the importance of the conformation of the
      domain in coat binding. These replacements strongly affected the ability of the
      scaffolding protein to interact with coat protein. The severity of the defect in
      the association of scaffolding protein to coat protein was dependent on location,
      with substitutions at residues in the turn and helix 2 causing the most
      significant effects. Substituting aspartic acid for hydrophobic interface
      residues dramatically perturbs the stability of the structure, but similar
      substitutions in the turn had much less effect on the integrity of this domain,
      as determined by circular dichroism. We propose that the binding of scaffolding
      protein to coat protein is dependent on angle of the beta-turn and the
      orientation of the charged surface on helix 2. Surprisingly, formation of the
      highly complex procapsid structure depends on a relatively simple interaction.

PMID- 22879596
TI  - The metalloprotease meprin beta generates amino terminal-truncated amyloid beta
      peptide species.
AB  - The amyloid beta (Abeta) peptide, which is abundantly found in the brains of
      patients suffering from Alzheimer disease, is central in the pathogenesis of this
      disease. Therefore, to understand the processing of the amyloid precursor protein
      (APP) is of critical importance. Recently, we demonstrated that the
      metalloprotease meprin beta cleaves APP and liberates soluble N-terminal APP (N
      APP) fragments. In this work, we present evidence that meprin beta can also
      process APP in a manner reminiscent of beta-secretase. We identified cleavage
      sites of meprin beta in the amyloid beta sequence of the wild type and Swedish
      mutant of APP at positions p1 and p2, thereby generating Abeta variants starting
      at the first or second amino acid residue. We observed even higher kinetic values
      for meprin beta than BACE1 for both the wild type and the Swedish mutant APP
      form. This enzymatic activity of meprin beta on APP and Abeta generation was also
      observed in the absence of BACE1/2 activity using a beta-secretase inhibitor and
      BACE knock-out cells, indicating that meprin beta acts independently of beta
      secretase.

PMID- 22879597
TI  - The heme oxygenase 1 inducer (CoPP) protects human cardiac stem cells against
      apoptosis through activation of the extracellular signal-regulated kinase
      (ERK)/NRF2 signaling pathway and cytokine release.
AB  - Intracoronary delivery of c-kit-positive human cardiac stem cells (hCSCs) is a
      promising approach to repair the infarcted heart, but it is severely limited by
      the poor survival of donor cells. Cobalt protoporphyrin (CoPP), a well known heme
      oxygenase 1 inducer, has been used to promote endogenous CO generation and
      protect against ischemia/reperfusion injury. Therefore, we determined whether
      preconditioning hCSCs with CoPP promotes CSC survival. c-kit-positive, lineage
      negative hCSCs were isolated from human heart biopsies. Lactate dehydrogenase
      release assays demonstrated that preconditioning CSCs with CoPP markedly enhanced
      cell survival after oxidative stress induced by H(2)O(2), concomitant with up
      regulation of heme oxygenase 1, COX-2, and anti-apoptotic proteins (BCL2, BCL2
      A1, and MCL-1) and increased phosphorylation of NRF2. Apoptotic cytometric assays
      showed that pretreatment of CSCs with CoPP enhanced the cells' resistance to
      apoptosis induced by oxidative stress. Conversely, knocking down HO-1, COX-2, or
      NRF2 by shRNA gene silencing abrogated the cytoprotective effects of CoPP.
      Further, preconditioning CSCs with CoPP led to a global increase in release of
      cytokines, such as EGF, FGFs, colony-stimulating factors, and chemokine ligand.
      Conditioned medium from cells pretreated with CoPP conferred naive CSCs
      remarkable resistance to apoptosis, demonstrating that cytokines released by
      preconditioned cells play a key role in the anti-apoptotic effects of CoPP.
      Preconditioning CSCs with CoPP also induced an increase in the phosphorylation of
      Erk1/2, which are known to modulate multiple pro-survival genes. These results
      potentially provide a simple and effective strategy to enhance survival of CSCs
      after transplantation and, therefore, their efficacy in repairing infarcted
      myocardium.

PMID- 22879598
TI  - Green tea polyphenols precondition against cell death induced by oxygen-glucose
      deprivation via stimulation of laminin receptor, generation of reactive oxygen
      species, and activation of protein kinase Cepsilon.
AB  - As the development of synthetic drugs for the prevention of stroke has proven
      challenging, utilization of natural products capable of preconditioning neuronal
      cells against ischemia-induced cell death would be a highly useful complementary
      approach. In this study using an oxygen-glucose deprivation and reoxygenation
      (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea
      polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate
      (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic
      interaction was observed between GTPP constituents, with unfractionated GTPP more
      potently preconditioning cells than EGCG. GTPP-induced preconditioning required
      the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR
      also mediated the generation of reactive oxygen species (ROS) via activation of
      NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce
      preconditioning, suggesting that sublethal levels of ROS are indeed an important
      mediator in GTPP-induced preconditioning. This role for ROS was further supported
      by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally,
      ROS induced an activation and translocation of protein kinase C (PKC),
      particularly PKCepsilon from the cytosol to the membrane/mitochondria, which was
      also blocked by antioxidants. The crucial role of PKC in GTPP-induced
      preconditioning was supported by use of its specific inhibitors. Preconditioning
      was increased by conditional overexpression of PKCepsilon and decreased by its
      knock-out with siRNA. Collectively, these results suggest that GTPP stimulates
      67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn
      induces activation of PKC, particularly prosurvival isoenzyme PKCepsilon,
      resulting in preconditioning against cell death induced by OGD/R.

PMID- 22879599
TI  - Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing
      receptor (ZnR/GPR39).
AB  - Zinc activates a specific Zn(2+)-sensing receptor, ZnR/GPR39, and thereby
      triggers cellular signaling leading to epithelial cell proliferation and
      survival. Epithelial cells that express ZnR, particularly colonocytes, face
      frequent changes in extracellular pH that are of physiological and pathological
      implication. Here we show that the ZnR/GPR39-dependent Ca(2+) responses in HT29
      colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by
      about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular
      acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor
      of this protein is located on an extracellular domain. ZnR/GPR39-dependent
      activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was
      abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was
      monitored for the ZnR/GPR39-dependent up-regulation of Na(+)/H(+) exchange
      activity at pH 6.5. Focusing on residues putatively facing the extracellular
      domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine
      residues forming the Zn(2+) binding site, His(17) or His(19), or other
      extracellular-facing histidines to alanine residues did not abolish the pH
      dependence of ZnR/GPR39. In contrast, replacing Asp(313) with alanine resulted in
      similar Ca(2+) responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant
      also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up
      regulation of Na(+)/H(+) exchange at pH 7.4 and pH 6.5. Substitution of Asp(313)
      to His or Glu residues restored pH sensitivity of the receptor. This indicates
      that Asp(313), which was shown to modulate Zn(2+) binding, is an essential
      residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense
      physiologically relevant changes in extracellular pH that thus regulate ZnR
      dependent signaling and ion transport activity.

PMID- 22879600
TI  - Corruption and spread of pathogenic proteins in neurodegenerative diseases.
AB  - With advancing age, the brain becomes increasingly susceptible to
      neurodegenerative diseases, most of which are characterized by the misfolding and
      errant aggregation of certain proteins. The induction of aggregation involves a
      crystallization-like seeding mechanism by which a specific protein is
      structurally corrupted by its misfolded conformer. The latest research indicates
      that, once formed, proteopathic seeds can spread from one locale to another via
      cellular uptake, transport, and release. Impeding this process could represent a
      unified therapeutic strategy for slowing the progression of a wide range of
      currently intractable disorders.

PMID- 22879601
TI  - A dichotomy in cortical actin and chemotactic actin activity between human memory
      and naive T cells contributes to their differential susceptibility to HIV-1
      infection.
AB  - Human memory and naive CD4 T cells can mainly be identified by the reciprocal
      expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO
      memory CD4 T cells are preferentially infected and serve as a major viral
      reservoir. The molecular mechanism dictating this differential susceptibility to
      HIV-1 remains largely obscure. Here, we report that the different susceptibility
      of memory and naive T cells to HIV is not determined by restriction factors such
      as Apobec3G or BST2. However, we observed a phenotypic distinction between human
      CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin
      dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be
      distinguished as CD45RO(+)Actin(high). In contrast, CD45RA T cells are
      phenotypically CD45RA(+)Actin(low). In addition, the cortical actin in CD45RO
      memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic
      induction by SDF-1, whereas that of naive cells cannot, despite a similar level
      of the chemokine receptor CXCR4 present on both cells. We further demonstrate
      that this difference in the cortical actin contributes to their differential
      susceptibility to HIV-1; resting memory but not naive T cells are highly
      responsive to HIV-mediated actin dynamics that promote higher levels of viral
      entry and early DNA synthesis in resting memory CD4 T cells. Furthermore,
      transient induction of actin dynamics in resting naive T cells rescues HIV latent
      infection following CD3/CD28 stimulation. These results suggest a key role of
      chemotactic actin activity in facilitating HIV-1 latent infection of these T cell
      subsets.

PMID- 22879602
TI  - Gemfibrozil, a lipid-lowering drug, increases myelin genes in human
      oligodendrocytes via peroxisome proliferator-activated receptor-beta.
AB  - An increase in CNS remyelination and a decrease in CNS inflammation are important
      steps to halt the progression of multiple sclerosis. Earlier studies have shown
      that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The
      current study identified another novel property of gemfibrozil in stimulating the
      expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte
      glycoprotein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, and proteolipid
      protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal
      cord organotypic cultures. Although gemfibrozil is a known activator of
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we were unable to
      detect PPAR-alpha in either gemfibrozil-treated or untreated human
      oligodendrocytes, and gemfibrozil increased the expression of myelin genes in
      oligodendrocytes isolated from both wild type and PPAR-alpha(-/-) mice. On the
      other hand, gemfibrozil markedly increased the expression of PPAR-beta but not
      PPAR-gamma. Consistently, antisense knockdown of PPAR-beta, but not PPAR-gamma,
      abrogated the stimulatory effect of gemfibrozil on myelin genes in human
      oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in
      oligodendroglia isolated from PPAR-beta(-/-) mice. Chromatin immunoprecipitation
      analysis showed that gemfibrozil induced the recruitment of PPAR-beta to the
      promoter of PLP and myelin oligodendrocyte glycoprotein genes in human
      oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment
      of PPAR-beta to the PLP promoter in vivo in the spinal cord of experimental
      autoimmune encephalomyelitis mice and suppression of experimental autoimmune
      encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results
      suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-beta
      and that gemfibrozil, a prescribed drug for humans, may find further therapeutic
      use in demyelinating diseases.

PMID- 22879604
TI  - Surgical technique: hand surgery in patients who are unable to adopt a supine
      position.

PMID- 22879603
TI  - The M-T hook structure is critical for design of HIV-1 fusion inhibitors.
AB  - CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal
      heptad repeat of gp41. We recently identified that its N-terminal residues Met
      626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus
      stabilizing the interaction of the inhibitor with the deep pocket on the N
      terminal heptad repeat. In this study, we further demonstrated that the M-T hook
      structure is a key determinant of CP621-652 in terms of its thermostability and
      anti-HIV activity. To directly define the structure and function of the M-T hook,
      we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N
      terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution
      crystal structure (1.9 A) of MT-C34 complexed by an N-terminal heptad repeat
      derived peptide reveals that the M-T hook conformation is well preserved at the N
      terminal extreme of the inhibitor. Strikingly, addition of two hook residues
      could dramatically enhance the binding affinity and thermostability of 6-helix
      bundle core. Compared with C34, MT-C34 exhibited significantly increased activity
      to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5
      fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher
      increase than C34 in blocking 6-helix bundle formation. We further showed that MT
      C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1
      variants. Therefore, this study provides convincing data for our proposed concept
      that the M-T hook structure is critical for designing HIV-1 fusion inhibitors.

PMID- 22879605
TI  - Dupuytren's disease in a rock climber with an unaffected identical twin.

PMID- 22879606
TI  - Complete genome sequences of novel canine noroviruses in Hong Kong.
AB  - We report the complete genome sequences of two novel isolates of norovirus
      isolated from the fecal swab specimens of dogs in Hong Kong. The complete viral
      genome is approximately 7.6 kb in length and consists of 3 overlapping open
      reading frames encoding the ORF1 polyprotein, VP1, and VP2, respectively.
      Analysis of the VP1 sequence suggested that these noroviruses are divergent from
      known noroviruses and may represent a novel phylogenetic clade within the genus.

PMID- 22879607
TI  - Complete Genome Sequence of a Novel Avian-Like H3N2 Swine Influenza Virus
      Discovered in Southern China.
AB  - We report here the complete genomic sequence of a novel avian-like H3N2 swine
      influenza virus containing an H5N1 highly pathogenic avian influenza virus
      segment that was obtained from swine in southern China. Phylogenetic analysis
      indicated that this virus might originate from domestic aquatic birds. The
      sequence information provided herein suggests that continuing study is required
      to determine if this virus can be established in the swine population and pose
      potential threats to public health.

PMID- 22879608
TI  - Papilio polyxenes densovirus has an iteravirus-like genome organization.
AB  - The genome of Papilio polyxenes densovirus was cloned and sequenced and contained
      5,053 nucleotides (nt), including inverted terminal repeats (ITRs) of 271 nt with
      terminal hairpins of 175 nt. Its DNA sequence and monosense organization with 3
      open reading frames (ORFs) are typical of the genus Iteravirus in the subfamily
      Densovirinae of the Parvoviridae.

PMID- 22879609
TI  - Complete genome sequence of porcine circovirus 2b strain CC1.
AB  - A porcine circovirus 2 (PCV2) strain, designated CC1, was isolated and purified
      from tissue samples from pigs with wasting syndromes in China. We report the
      complete genome sequence of PCV2b strain CC1 with a deletion of C at position
      1053 resulting in elongation of open reading frame 2 (ORF2) and formation of
      ORF5. There were 11 ORFs in the genome.

PMID- 22879610
TI  - Complete genome sequence of Pseudomonas aeruginosa siphophage MP1412.
AB  - We report the complete genome sequence of Pseudomonas aeruginosa siphophage
      MP1412, which displays synteny to those of P. aeruginosa phages M6 and YuA.
      However, the presence of two homing endonucleases of the GIY-YIG family is unique
      to MP1412, suggesting their unique role in the phage life cycle of the bacterial
      host.

PMID- 22879611
TI  - Complete genome sequence of bacteriophage BC-611 specifically infecting
      Enterococcus faecalis strain NP-10011.
AB  - Enterococcus faecalis is an opportunistic pathogen that causes serious infections
      in humans and animals and is also an important bacterium for dairy and probiotic
      supplement production. Therefore, bacteriophages infecting E. faecalis may be
      useful for phage therapy against multidrug-resistant strains or may threaten
      industrial fermentation. We isolated a virulent Siphoviridae bacteriophage, BC
      611, specifically infecting E. faecalis strain NP-10011 but not infecting other
      E. faecalis strains or other enterococci. Although the genome sequence of BC-611
      resembled that of enterococcal bacteriophage SAP6, BC-611 was marked by its
      narrow host specificity.

PMID- 22879612
TI  - Genome sequence of herpes simplex virus 1 strain McKrae.
AB  - The herpes simplex virus 1 (HSV-1) strain McKrae is highly virulent compared to
      other wild-type strains of HSV-1. To help us better understand the genetic
      determinants that lead to differences in the pathogenicity of McKrae and other
      HSV-1 strains, we sequenced its genome. Comparing the sequence of McKrae's genome
      to that of strain 17 revealed that the genomes differ by at least 752 single
      nucleotide polymorphisms (SNPs) and 86 insertion/deletion events (indels).
      Although the majority of these polymorphisms reside in noncoding regions, 241
      SNPs and 10 indels alter the protein-coding sequences of 58 open reading frames.
      Some of these variations are expected to contribute to the pathogenic phenotype
      of McKrae.

PMID- 22879613
TI  - Complete genome sequence of an avian-like H4N8 swine influenza virus discovered
      in southern China.
AB  - We report here the complete genomic sequence of an avian-like H4N8 swine
      influenza virus containing an H5N1 avian influenza virus segment from swine in
      southern China. Phylogenetic analyses of the sequences of all eight viral RNA
      segments demonstrated that these are wholly avian influenza viruses of the Asia
      lineage. To our knowledge, this is the first report of interspecies transmission
      of an avian H4N8 influenza virus to domestic pigs under natural conditions.

PMID- 22879614
TI  - Complete genome sequence of a novel variant porcine reproductive and respiratory
      syndrome virus (PRRSV) strain: evidence for recombination between vaccine and
      wild-type PRRSV strains.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiologic
      agent of porcine reproductive and respiratory syndrome (PRRS), which can evolve
      continuously by random mutation or intragenic recombination. Here we report the
      complete genomic sequence of a PRRSV variant with nucleotide acid deletions and
      insertions in the nonstructural protein 2 (nsp2) gene and a possible
      recombination event between a modified live virus (MLV) vaccine strain and a
      prototype Chinese field strain.

PMID- 22879615
TI  - The Genome of Pieris rapae Granulovirus.
AB  - Pieris rapae granulovirus (PrGV) can infect and kill larvae of Pieris rapae, a
      worldwide and important pest of mustard family crops. The PrGV genome consists of
      108,592 bp, is AT rich (66.8%), and is most structurally and organizationally
      similar to the Choristoneura occidentalis granulovirus genome. Of the predicted
      120 open reading frames (ORFs), 32 genes specifically occurred in GVs, including
      four genes unique to PrGV (Pr9, Pr32, Pr53, and Pr117).

PMID- 22879616
TI  - Complete genome sequence of a novel vitivirus isolated from grapevine.
AB  - A novel virus-like sequence from grapevine was identified by Illumina sequencing.
      The complete genome is 7,551 nucleotides in length, with polyadenylation at the
      3' end. Translation of the sequence revealed five open reading frames (ORFs). The
      genomic organization was most similar to those of vitiviruses. The polymerase
      (ORF1) and coat protein (ORF4) genes shared 31 to 49% nucleotide and 40 to 70%
      amino acid sequence identities, respectively, with other grapevine vitiviruses.
      The virus was tentatively named grapevine virus F (GVF).

PMID- 22879617
TI  - Characterization and complete genome sequence of human coronavirus NL63 isolated
      in China.
AB  - Human coronavirus NL63 (HCoV-NL63) was first discovered in Amsterdam in 2004 and
      was identified as a new human respiratory coronavirus. We here report the first
      complete genome sequence of HCoV-NL63 strain CBJ 037 isolated in 2008 from a
      patient with bronchitis in Beijing, China.

PMID- 22879618
TI  - Complete genome sequence of an avian-origin H3N2 canine influenza virus isolated
      from dogs in South Korea.
AB  - An avian-origin Korean H3N2 canine influenza virus (CIV) strain, designated
      A/canine/Korea/01/2007 (H3N2), was isolated from nasal swabs of pet dogs
      exhibiting severe respiratory syndrome in 2007. In the present study, we report
      the first complete genome sequence containing 3' and 5' noncoding regions (NCRs)
      of H3N2 CIV, which will provide important insights into the molecular basis of
      pathogenesis, transmission, and evolution of CIV.

PMID- 22879619
TI  - Complete genome sequencing of a novel newcastle disease virus isolate circulating
      in layer chickens in the Dominican Republic.
AB  - Newcastle disease virus (NDV) was isolated from an outbreak in layer chickens in
      the Dominican Republic in 2008. Infections with this isolate led to a 100%
      apparent case fatality rate in birds. Complete genome sequencing revealed that
      the isolate does not belong to any of the previously described NDV genotypes.
      Similarly, large differences were observed in the amino acid sequence of the
      fusion and hemagglutinin-neuraminidase proteins in comparison with all known NDV
      genotypes, suggesting the existence of an unknown reservoir for NDV. The work
      presented here represents the first complete genome sequence of NDV in the
      Dominican Republic.

PMID- 22879620
TI  - Complete genome sequence of a highly prevalent isolate of porcine epidemic
      diarrhea virus in South China.
AB  - A widespread porcine epidemic diarrhea virus (PEDV) occurred in southern China
      during 2010 to 2012. A virulent field PEDV strain, GD-B, was isolated from a
      sucking piglet suffering from severe diarrhea in Guangdong, China. We sequenced
      and analyzed the complete genome of strain GD-B, which will promote a better
      understanding of the molecular epidemiology and genetic diversity of PEDV field
      isolates in southern China.

PMID- 22879621
TI  - Genome sequence of a novel actinophage PIS136 isolated from a strain of
      Saccharomonospora sp.
AB  - A wide-host-range bacteriophage (phage) PIS136 was isolated from PA136, a strain
      of Saccharomonospora belonging to the group actinomycetes. Here, we present the
      genome sequence of the PIS136 phage, which is 94,870 bp long and contains 132
      putative coding sequences and one tRNA gene. An IS element-like region with two
      genes for putative transposases was identified in the genome. The presence of IS
      element-like sequences suggests that PIS136 is still under active evolution.

PMID- 22879622
TI  - Genome sequence of a novel reassortant H3N2 avian influenza virus in southern
      China.
AB  - The distribution and prevalence of H3 subtype influenza viruses in avian and
      mammalian hosts constitutes a potential threat to both human and avian health. We
      report a complete genome sequence of a novel reassortant H3N2 avian influenza
      virus. Phylogenetic analysis showed that HA and NA showed the highest sequence
      homologies with those of A/white-backed munia/Hong Kong/4519/2009 (H3N2).
      However, the internal genes had the highest sequence homologies with those of H6
      and H7 subtypes. The data provide further evidence of the existence of a natural
      reassortant H3N2 strain in southern China.

PMID- 22879623
TI  - Complete genome sequence of a novel pararetrovirus isolated from soybean.
AB  - We report the complete genome sequence of soybean Putnam virus (SPuV), a new
      pararetrovirus isolated from a soybean field in Putnam County, OH. Comparison of
      SPuV with other plant-infecting pararetroviruses places it in the genus
      Caulimovirus of the family Caulimoviridae.

PMID- 22879624
TI  - Autologous T cells on the attack against AML.
AB  - In this issue of Blood, Greiner and colleagues describe how peptides derived from
      the mutated nucleophosmin 1 gene (NPM1(mut)) can elicit in vitro CD4(+) and
      CD8(+) T-cell responses in patients with acute myeloid leukemia, which can lead
      to antigen-specific lysis of leukemic blasts.

PMID- 22879625
TI  - A second hit for TMA.
AB  - In this issue of Blood, Fuchs and colleagues provide evidence that circulating
      DNA and histones, presumably released from neutrophils, would be the second hit
      for development of thrombotic microangiopathies (TMAs), a group of life
      threatening disorders characterized by thrombi in the microvasculature resulting
      in thrombocytopenia, microangiopathic hemolysis, and organ dysfunction.

PMID- 22879626
TI  - The functional dissonance of platelets.

PMID- 22879627
TI  - The changing spectrum of rheumatic disease in HIV infection.
AB  - BACKGROUND: Rheumatic manifestations were described soon after human
      immunodeficiency virus (HIV) was discovered. Since however, combination anti
      retroviral therapy (cART) has revolutionized the course of the infection. Less
      clear is what effect cART has had on rheumatic manifestations. SOURCES OF DATA:
      References were retrieved from the PubMed database using keywords including:
      'HIV' and 'arthritis'; 'myalgia'; 'arthralgia' and other disease-specific terms,
      e.g. 'rheumatoid arthritis'. AREAS OF AGREEMENT: Musculoskeletal pain was common
      in HIV and increased with AIDS. Immune restoration inflammatory syndrome on
      initiation of cART causes de novo autoimmune inflammatory rheumatic disorders.
      Seronegative inflammatory arthritis with/without axial involvement has been
      reported widely with HIV. AREAS OF CONTROVERSY: It is unclear if HIV causes these
      conditions, creates an environmental milieu supportive of these conditions or
      acts as a marker of other risk factors. It is unclear what effect cART has had on
      these conditions. GROWING POINTS: Variable diagnostic classification criteria
      have caused this literature to be poorly comparable. AREAS TIMELY FOR DEVELOPING
      RESEARCH: High-quality controlled epidemiological studies using standardized
      criteria are needed among cART users. Treatment of active autoimmune disease in
      HIV patients needs to be evaluated formally.

PMID- 22879628
TI  - The amyloid precursor protein (APP) family members are key players in S
      adenosylmethionine formation by MAT2A and modify BACE1 and PSEN1 gene expression
      relevance for Alzheimer's disease.
AB  - Central hallmark of Alzheimer's disease are senile plaques mainly composed of
      beta-amyloid, which is a cleavage product of the amyloid precursor protein (APP).
      The physiological function of APP and its family members APLP1 and APLP2 is
      poorly understood. In order to fill this gap, we established a cell-culture based
      model with simultaneous knockdown of all members of the family. A comprehensive
      proteome study of the APP/APLP1/APLP2 knockdown cell lysates versus controls
      revealed significant protein abundance changes of more than 30 proteins. Targeted
      validation of selected candidates by immunoblotting supported the significant
      down-regulation of the methionine adenosyltransferase II, alpha (MAT2A) as well
      as of peroxiredoxin 4 in the knockdown cells. Moreover, MAT2A was significantly
      down-regulated at the mRNA level as well. MAT2A catalyzes the production of S
      adenosylmethionine from methionine and ATP, which plays a pivotal role in the
      methylation of neurotransmitters, DNA, proteins, and lipids. MAT2A-dependent
      significant up-regulation of S-adenosylmethionine was also detectable in the
      knockdown cells compared with controls. Our results point to a role of the APP
      family proteins in cellular methylation mechanisms and fit to findings of
      disturbed S-adenosylmethionine levels in tissue and CSF of Alzheimer disease
      patients versus controls. Importantly, methylation plays a central role for
      neurotransmitter generation like acetylcholine pointing to a crucial relevance of
      our findings for Alzheimer's disease. In addition, we identified differential
      gene expression of BACE1 and PSEN1 in the knockdown cells, which is possibly a
      consequence of MAT2A deregulation and may indicate a self regulatory mechanism.

PMID- 22879629
TI  - Longitudinal changes in thyroid function in the oldest old and survival: the
      cardiovascular health study all-stars study.
AB  - CONTEXT: Data on thyroid function in the oldest old are sparse, and existing
      studies show conflicting evidence on the relationship between thyroid function
      and mortality in this age group. OBJECTIVE: We describe longitudinal changes in
      thyroid function in a cohort of elderly individuals and determine the
      relationship between thyroid function and mortality. DESIGN, SETTING, AND
      PARTICIPANTS: Eight hundred forty-three participants in the Cardiovascular Health
      Study All Stars Study who were not taking thyroid medications and had thyroid
      function testing in 2005-2006 (mean age 85 yr). MAIN OUTCOME MEASURE: Thyroid
      stimulating hormone (TSH), free T(4) (FT4), total T(3), and thyroid peroxidase
      antibody status were measured in 1992-1993 and 2005-2006. Deaths were ascertained
      through February 2011. RESULTS: There was a statistically significant 13%
      increase in TSH, 1.7% increase in FT4, and 13% decrease in total T(3) over the 13
      yr period. Two hundred eighty-seven deaths occurred over a median follow-up of
      5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio
      (HR) 0.97, 95% confidence interval (CI) 0.66-1.43], TSH level (HR per milliunits
      per liter 0.94, 95% CI 0.88-1.01), or persistent thyroid peroxidase antibody
      positivity (HR 1.09, 95% CI 0.62-1.92), and death. However, FT4 was positively
      associated with death (HR per nanograms per deciliter 2.57, 95% CI 1.32-5.02).
      CONCLUSIONS: TSH increased over time in these older individuals. This elevation
      was not associated with increased or decreased mortality, although higher FT4
      levels were associated with death. These findings raise concern for treatment of
      mild elevations of TSH in advanced age. Further studies are needed to determine
      the potential benefit of treating age-related changes in thyroid function.

PMID- 22879630
TI  - Atorvastatin reduces malondialdehyde concentrations in patients with polycystic
      ovary syndrome.
AB  - BACKGROUND: It has been shown that there is an increase in oxidative stress in
      polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic
      effect other than their lipid-lowering effect. These effects may be mediated in
      part by reducing oxidative stress. METHODS: This randomized, double-blind,
      placebo-controlled study was conducted to assess the effect of atorvastatin on
      serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in
      patients with PCOS. Forty medication-naive patients with PCOS were randomized to
      either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension
      study for both groups of patients was undertaken with metformin 1500 mg daily
      after completing initial 3 months of atorvastatin or placebo. RESULTS: There was
      a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29
      (0.04) vs. 0.25 (0.02) MUmol/liter; P < 0.01] compared with placebo [0.28 (0.02)
      vs. 0.29 (0.12) MUmol/liter; P = 0.52]. Three months treatment with metformin
      resulted in further reduction of MDA levels with atorvastatin compared with
      baseline [0.25 (0.02) baseline vs. 0.23 (0.03) MUmol/liter for atorvastatin
      treated; P = 0.02]. There was also a significant correlation between the
      reduction in MDA with a reduction in high-sensitivity C-reactive protein (r =
      0.71, P < 0.01), an increase in 25-hydroxyvitamin D (25OHD; r = -0.68, P = 0.02),
      and a reduction in testosterone levels (r = 0.63, P = 0.01). Multiple linear
      regression analysis revealed Delta25OHD, DeltaC-reactive protein, and
      Deltatestosterone were independent predictors of changes in MDA after
      atorvastatin treatment. No correlation was observed between the reductions in
      serum MDA concentrations with changes in the lipid parameters. CONCLUSIONS:
      Twelve weeks of atorvastatin led to a significant reduction in oxidative stress
      as determined by MDA concentrations among patients with polycystic ovary syndrome
      that was independently predicted by changes in testosterone, 25OHD, and high
      sensitivity C-reactive protein.

PMID- 22879631
TI  - Plasma sphingosine 1-phosphate levels and the risk of vertebral fracture in
      postmenopausal women.
AB  - CONTEXT: Although sphingosine 1-phosphate (S1P) plays diverse roles in bone
      metabolism, the most prominent role seems to be the augmentation of bone
      resorption. OBJECTIVE: The objective of the study was to investigate the
      possibility of using S1P as a predictor for osteoporotic vertebral fracture (VF)
      risk. DESIGN AND SETTING: This was a case-control study conducted in a clinical
      unit in Korea. PARTICIPANTS: Sixty-nine cases having radiological VF and 69 age-
      and body mass index-matched controls among 460 eligible postmenopausal women
      participated in the study. MAIN OUTCOME MEASURES: Lateral thoracolumbar
      radiographs, bone mineral density (BMD), bone turnover markers, and plasma S1P
      levels were obtained from all subjects. RESULTS: S1P levels were markedly higher
      in subjects with VF (7.49+/-3.44 MUmol/liter) than in those without VF (5.58+/
      2.01 MUmol/liter; P=0.001) and increased in a dose-response manner as the number
      of VF increased (P for the trend<0.001), even after adjustment for lumbar spine
      BMD and potential confounders. The odds ratio for VF was markedly higher in
      subjects in the highest S1P quartile category compared with those in the lowest
      S1P quartile category after adjustment for confounders (odds ratio 9.33, 95%
      confidence interval 2.68-32.49). S1P levels were inversely correlated with BMD at
      various sites (P=0.015 to 0.044), whereas they were positively correlated with
      bone resorption markers (P=0.016 to 0.098). CONCLUSION: These findings suggest
      that plasma S1P may be a potential biomarker for the risk of VF, independent of
      BMD, in postmenopausal women.

PMID- 22879632
TI  - Pancreatic volume is reduced in adult patients with recently diagnosed type 1
      diabetes.
AB  - CONTEXT: Pancreatic atrophy is common in longstanding type 1 diabetes, but there
      are limited data concerning pancreas size at diagnosis. OBJECTIVE: Our objective
      was to determine whether pancreatic size was reduced in patients with recently
      diagnosed type 1 diabetes and assess whether pancreatic volume was related to
      residual beta-cell function or islet autoantibodies. DESIGN AND SETTING: We
      conducted a controlled cohort study with strict inclusion criteria, recruiting
      from hospital diabetes clinics between 2007 and 2010. PATIENTS AND HEALTHY
      CONTROLS: Participants included 20 male adult patients (median age 27 yr) with
      recent-onset type 1 diabetes (median duration 3.8 months) and 24 male healthy
      controls (median age 27 yr). INTERVENTION: Interventions included noninvasive
      magnetic resonance imaging, collection of fasting blood samples, and glucagon
      stimulation testing in patients. MAIN OUTCOME MEASURES: We compared pancreatic
      volume estimates between patients with recent-onset type 1 diabetes and healthy
      controls as planned a priori. RESULTS: Scans were analyzed by an experienced
      radiologist blinded to diabetes status. Pancreatic volume correlated with body
      weight in patients and controls (P = 0.007). After adjustment for body weight,
      mean pancreatic volume index was 26% less in patients (1.19 ml/kg, se 0.07 ml/kg)
      than in controls (1.61 ml/kg, se 0.08 ml/kg) (P = 0.001). No correlation was seen
      between pancreatic volume index in patients and diabetes duration, glucose or C
      peptide levels, glycated hemoglobin, and islet autoantibodies. CONCLUSIONS:
      Pancreatic volume is reduced by 26% in patients with type 1 diabetes within
      months of diagnosis, suggesting that atrophy begins years before the onset of
      clinical disease. Pancreatic atrophy within individuals is therefore a potential
      clinical marker of disease progression.

PMID- 22879633
TI  - Racial/ethnic differences in sex hormone levels among postmenopausal women in the
      diabetes prevention program.
AB  - CONTEXT: Sex hormones may differ by race/ethnicity in postmenopausal women.
      Whether racial/ethnic differences also exist among those who are overweight and
      glucose intolerant is not clear. OBJECTIVES: The objective of the study was to
      compare sex hormones by race/ethnicity [non-Hispanic white (NHW), Hispanic,
      African-American (AA)] in overweight, glucose-intolerant, postmenopausal women.
      DESIGN: This was a secondary analysis of a randomized controlled trial.
      PARTICIPANTS: Participants included postmenopausal glucose-intolerant women
      participating in the Diabetes Prevention Program. INTERVENTIONS: Interventions
      included intensive lifestyle modification (consisting of diet and physical
      activity) or metformin 850 mg twice a day vs. placebo. MAIN OUTCOME MEASURES:
      Baseline levels and 1-yr intervention-related changes in SHBG, total and
      bioavailable estradiol (E2), total and bioavailable testosterone, and
      dehydroepiandrosterone were measured. RESULTS: At baseline, among women not using
      estrogen (n = 370), NHW had higher total and bioavailable E2 and testosterone
      levels than Hispanics independent of age, type of menopause, waist circumference,
      alcohol intake, and current smoking. NHW also had higher levels of bioavailable
      E2 and lower levels of SHBG than AA. At baseline, among estrogen users (n = 310),
      NHW had higher total and bioavailable E2 than Hispanics and higher levels of SHBG
      than AA after adjustment. At 1 yr, among women not using estrogen, NHW had larger
      declines in total E2 and bioavailable E2 levels than AA after adjustment for the
      above covariates, changes in waist circumference, and randomization arm. At 1 yr,
      among estrogen users, sex hormone changes did not differ by race/ethnicity.
      CONCLUSIONS: Among postmenopausal women, there were significant race/ethnicity
      differences in baseline sex hormones and changes in sex hormones.

PMID- 22879634
TI  - Nurse leadership and patient safety.

PMID- 22879635
TI  - Magnetic resonance imaging of sagittal structures in the knee.

PMID- 22879636
TI  - Coronal oblique proton density weighted magnetic resonance imaging of the right
      shoulder.

PMID- 22879637
TI  - An unusual case of pneumonia.

PMID- 22879638
TI  - The role of poverty in explaining health variations in 7-year-old children from
      different family structures: findings from the UK Millennium Cohort Study.
AB  - BACKGROUND: Despite rises in reconstituted and lone-parent families, relatively
      little is known about how the health of children in different family types
      varies, and the extent to which any differences might be explained by poverty.
      The authors examined this using cross-sectional data on 13 681 seven-year-olds
      from the Millennium Cohort Study. METHODS: The authors estimated RRs and 95% CIs
      for having poor physical (general health, long-standing illness, injury,
      overweight, asthma, fits) and mental health (using strengths and difficulties
      scores) according to family structure using Poisson regression. The authors
      adjusted for confounders (aRR) and then investigated the role of poverty as a
      mediator by entering a poverty score (based on income, receipt of benefits,
      subjective poverty and material deprivation) into the main model. RESULTS:
      Children living in reconstituted and lone-parent families were at a slight
      increased risk of poor health compared with those living with two natural
      parents. Adjusting for poverty tended to remove the elevated risk of poor
      physical health in children living in lone-parent and reconstituted families.
      However, for the mental health outcomes, poverty tended to remove the elevated
      risk for lone parents but not for reconstituted families. For example, the aRR
      for borderline-abnormal total difficulties fell from 1.45 (1.22 to 1.72) to 1.34
      (1.13 to 1.59) in children living in reconstituted families and from 1.29 (1.14
      to 1.45) to 1.05 (0.92 to 1.19) in those living with lone parents. CONCLUSIONS:
      Poor physical and mental health was slightly more prevalent in children living in
      lone-parent or reconstituted families. Poverty reduction may help to reduce these
      differences, especially for children living with lone parents; however,
      alternative mechanisms should be also explored, particularly for children living
      in reconstituted families.

PMID- 22879639
TI  - Association between pre-eclampsia and locally derived traffic-related air
      pollution: a retrospective cohort study.
AB  - BACKGROUND: Pre-eclampsia is a common complication of pregnancy and is a major
      cause of fetal-maternal mortality and morbidity. Despite a number of plausible
      mechanisms by which air pollutants might contribute to this process, few studies
      have investigated the association between pre-eclampsia and traffic emissions, a
      major contributor to air pollution in urban areas. OBJECTIVE: The authors
      investigated the association between traffic-related air pollution and risk of
      pre-eclampsia in a maternal population in the urban centre of Perth, Western
      Australia. METHOD: The authors estimated maternal residential exposure to a
      marker for traffic-related air pollution (nitrogen dioxide, NO(2)) during
      pregnancy for 23 452 births using temporally adjusted land-use regression.
      Logistic regression was used to investigate associations with pre-eclampsia.
      RESULTS: Each IQR increase in levels of traffic-related air pollution in whole
      pregnancy and third trimester was associated with a 12% (1%-25%) and 30% (7%-58%)
      increased risk of pre-eclampsia, respectively. The largest effect sizes were
      observed for women aged younger than 20 years or 40 years or older, aboriginal
      women and women with pre-existing and gestational diabetes, for whom an IQR
      increase in traffic-related air pollution in whole pregnancy was associated with
      a 34% (5%-72%), 35% (0%-82%) and 53% (7%-219%) increase in risk of pre-eclampsia,
      respectively. CONCLUSIONS: Elevated exposure to traffic-related air pollution in
      pregnancy was associated with increased risk of pre-eclampsia. Effect sizes were
      highest for elevated exposures in third trimester and among younger and older
      women, aboriginal women and women with diabetes.

PMID- 22879640
TI  - Spending on mental health services in England fell in 2011-12.

PMID- 22879641
TI  - Healthcare in Syria is close to collapse as drug shortages bite.

PMID- 22879642
TI  - ADHD affects 3% of adults over 60, Dutch study finds.

PMID- 22879643
TI  - Advertising watchdog orders website to remove claims linking MMR vaccine with
      autism.

PMID- 22879644
TI  - Delirium is a strong risk factor for dementia in the oldest-old: a population
      based cohort study.
AB  - Recent studies suggest that delirium is associated with risk of dementia and also
      acceleration of decline in existing dementia. However, previous studies may have
      been confounded by incomplete ascertainment of cognitive status at baseline.
      Herein, we used a true population sample to determine if delirium is a risk
      factor for incident dementia and cognitive decline. We also examined the effect
      of delirium at the pathological level by determining associations between
      dementia and neuropathological markers of dementia in patients with and without a
      history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those
      eligible) aged >=85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was
      performed in 52%. Fixed and random-effects regression models were used to assess
      associations between (i) delirium and incident dementia and (ii) decline in Mini
      Mental State Examination scores in the whole group. The relationship between
      dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy
      body) was modelled, stratified by history of delirium. Delirium increased the
      risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1-35).
      Delirium was also associated with worsening dementia severity (odds ratio 3.1,
      95% confidence interval 1.5-6.3) as well as deterioration in global function
      score (odds ratio 2.8, 95% confidence interval 1.4-5.5). In the whole study
      population, delirium was associated with loss of 1.0 more Mini-Mental State
      Examination points per year (95% confidence interval 0.11-1.89) than those with
      no history of delirium. In individuals with dementia and no history of delirium
      (n = 232), all pathologies were significantly associated with dementia. However,
      in individuals with delirium and dementia (n = 58), no relationship between
      dementia and these markers was found. For example, higher Braak stage was
      associated with dementia when no history of delirium (odds ratio 2.0, 95%
      confidence interval 1.1-3.5, P = 0.02), but in those with a history of delirium,
      there was no significant relationship (odds ratio 1.2, 95% confidence interval
      0.2-6.7, P = 0.85). This trend for odds ratios to be closer to unity in the
      delirium and dementia group was observed for neuritic amyloid, apolipoprotein
      epsilon status, presence of infarcts, alpha-synucleinopathy and neuronal loss in
      substantia nigra. These findings are the first to demonstrate in a true
      population study that delirium is a strong risk factor for incident dementia and
      cognitive decline in the oldest-old. However, in this study, the relationship did
      not appear to be mediated by classical neuropathologies associated with dementia.

PMID- 22879645
TI  - Thumb arthroplasties.

PMID- 22879646
TI  - Re: Chiriac et al. Experience of using the bioresorbable copolyester poly(DL
      lactide-epsilon-caprolactone) nerve conduit guide NeurolacTM for nerve repair in
      peripheral nerve defects: report on a series of 28 lesions. J Hand Surg Eur.
      2011, 37: 342-9.

PMID- 22879647
TI  - Theopold C, Potter S, Dempsey M, O'Shaughnessy M. A randomised controlled trial
      of absorbable versus non-absorbable sutures for skin closure after open carpal
      tunnel release. J Hand Surg Eur. 2012; 37: 350-3.

PMID- 22879649
TI  - The roles of implicit memory bias, depression, and metacognitions in men and
      women with coronary artery disease.
AB  - The purpose of this research was to examine the role of implicit memory bias,
      depression, and metacognitions in coronary artery disease (CAD) and the
      relationships between implicit memory bias, depression, and metacognitions based
      on gender, age, and educational status. Participants were 30 patients with CAD
      and controls who were selected through a purposive sampling method in Iran. A
      demographic questionnaire, the Meta-Worry Questionnaire-30; the Beck's Depression
      Inventory-II; and the Word Stem Completion Software were used in this study.
      Resulting data demonstrated that patients with CAD had significant higher levels
      of depression, metacognitive worry, and negative-mood-inducing words than
      individuals in the control group. Also, individuals in the control group had
      significant higher performance on neutral-mood-inducing words than patients with
      CAD. Depression and metacognitive variables were significantly related to
      negative- and neutral-mood-inducing words in the total sample. Findings did not
      support significant relationships of age and educational level to depression,
      metacognition, and the implicit memory bias in males and females.

PMID- 22879650
TI  - Correlates of hepatitis B virus and HIV knowledge among gay and bisexual homeless
      young adults in Hollywood.
AB  - Homeless gay and bisexual (G/B) young men have multiple risk factors that
      increase their risk of contracting hepatitis B virus (HBV) and human
      immunodeficiency virus (HIV). This study used baseline information from
      structured instruments to assess correlates of knowledge to HIV and HBV infection
      from 267 young (18-39 year old) G/B active methamphetamine, cocaine, and crack
      using homeless men enrolled in a longitudinal trial. The study is designed to
      reduce drug use and improve knowledge of hepatitis and HIV/AIDS in a community
      center in Hollywood, California. Regression modeling revealed that previous
      hepatitis education delivered to G/B men was associated with higher levels of
      HIV/AIDS and hepatitis knowledge. Moreover, higher HIV/AIDS knowledge was
      associated with combining sex and drinking alcohol. Associations with hepatitis B
      knowledge was found among G/B men who were engaging in sex while under the
      influence of marijuana, who were receiving support from non-drug users, and who
      had been homeless in the last 4 months. Although being informed about HIV/AIDS
      and hepatitis did not preclude risky sexual and drug use behavior, knowledge
      about the dangers of concurrent sex with substance use is important. As higher
      levels of knowledge of hepatitis was associated with more moderate drug use,
      early access to testing and teaching harm reduction strategies remain critical to
      reduce exposure and infection of HBV and HIV in this population.

PMID- 22879651
TI  - Componential model of reading (CMR): validation studies.
AB  - The three current models of identifying learning disabilities: discrepancy model,
      RtI, and Componential Model of reading are discussed in terms of their utility.

PMID- 22879652
TI  - Minimal invasive cardiac output monitoring: get the dose of fluid right.

PMID- 22879653
TI  - Prevention of opioid-induced hyperalgesia in surgical patients: does it really
      matter?

PMID- 22879654
TI  - Non-invasive ventilation for weaning, avoiding reintubation after extubation and
      in the postoperative period: a meta-analysis.
AB  - Non-invasive ventilation (NIV) is a supportive therapy that improves mortality in
      acute respiratory failure (RF). It may also be used in patients recently
      extubated in intensive care units (ICUs), after operation, and to aid weaning
      from mechanical ventilation (MV) by reducing the morbidity and mortality
      associated with further MV. A meta-analysis of the available evidence was
      performed on the use of NIV in three areas: weaning, reduction in reintubation
      rates post-extubation on ICU, and reduction in RF after major surgery. Sixteen
      relevant randomized controlled trials were identified by three reviewers after a
      detailed search of identified medical databases. A meta-analysis of summary
      statistics relating to predetermined endpoints (ICU and hospital length of stay,
      ICU and hospital mortality, reintubation, pneumonia) was performed. NIV reduced
      the ICU length of stay when used for weaning (5.12 days) and post-surgery (0.44
      days). NIV reduced reintubation rates post-surgery [odds ratio (OR) 0.24, 95%
      confidence interval (CI) 0.12-0.50] and the incidence of pneumonia in weaning (OR
      0.12, 95% CI 0.05-0.31) and post-surgery (OR 0.27, 95% CI 0.09-0.77). There was
      insufficient evidence to suggest that NIV improves ICU survival, but an increased
      hospital survival in post-surgery (OR 4.54, [corrected] 95% CI 1.35-15.31) and a
      reduction after weaning (OR 0.55, 95% CI 0.31-0.98) [corrected] was seen. A meta
      analysis of NIV use in selected subgroups of recently extubated patients suggests
      that the judicious NIV use may reduce ICU and hospital length of stay, pneumonia,
      and reintubation rates and hospital survival.

PMID- 22879655
TI  - Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond
      vasospasm.
AB  - Despite improvements in the clinical management of aneurysmal subarachnoid
      haemorrhage over the last decade, delayed cerebral ischaemia (DCI) remains the
      single most important cause of morbidity and mortality in those patients who
      survive the initial bleed. The pathological mechanisms underlying DCI are still
      unclear and the calcium channel blocker nimodipine remains the only therapeutic
      intervention proven to improve functional outcomes after SAH. The recent failure
      of the drug clazosentan to improve functional outcomes despite reducing
      vasoconstriction has moved the focus of research into DCI away from cerebral
      artery constriction towards a more multifactorial aetiology. Novel pathological
      mechanisms have been suggested, including damage to cerebral tissue in the first
      72 h after aneurysm rupture ('early brain injury'), cortical spreading
      depression, and microthrombosis. A greater understanding of the significance of
      these pathophysiological mechanisms and potential genetic risk factors is
      required, if new approaches to the prophylaxis, diagnosis, and treatment of DCI
      are to be developed. Furthermore, objective and reliable biomarkers are needed
      for the diagnosis of DCI in poor grade SAH patients requiring sedation and to
      assess the efficacy of new therapeutic interventions. The purpose of this article
      is to appraise these recent advances in research into DCI, relate them to current
      clinical practice, and suggest potential novel avenues for future research.

PMID- 22879656
TI  - Effect of dexamethasone on nausea, vomiting, and pain in paediatric
      tonsillectomy.
AB  - BACKGROUND: The efficacy of dexamethasone (DEX) to reduce morbidity after
      paediatric tonsillectomy remains controversial. We evaluated the effect of 0.15
      and 0.5 mg kg(-1) DEX on the incidence of postoperative nausea and vomiting
      (PONV) and on pain intensity after paediatric tonsillectomy. METHODS: A total of
      147 children aged 2-8 yr undergoing elective tonsillectomy were included in this
      prospective randomized double-blind study. At the induction of anaesthesia,
      subjects received 0.15 mg kg(-1) (DEX 0.15), 0.5 mg kg(-1) (DEX 0.5) DEX, or an
      equivalent volume of saline solution (placebo). Anaesthetic and surgical
      techniques were standardized. The incidence of PONV and the need for anti-emetic
      drugs and additional analgesia (tramadol and/or morphine) were recorded.
      Postoperative pain was assessed using the Children's Hospital of Eastern Ontario
      Pain Scale, the visual analogue scale, and the postoperative pain measure for
      parents. RESULTS: The incidence of early PONV (primary outcome variable) was
      lower in both DEX groups (DEX 0.15: 21%; DEX 0.5: 22%; placebo: 49%; P=0.001).
      The incidence of severe pain was reduced in the DEX groups on the second
      postoperative day (DEX 0.15: 20%; DEX 0.5: 5%; placebo: 47%; P<0.001). The study
      was not powered to assess a difference between the two DEX dose groups.
      CONCLUSIONS: A single i.v. injection of DEX at the induction of anaesthesia was
      effective in reducing the incidence of early and late PONV and the level of pain
      on the second postoperative day. A 0.15 mg kg(-1) DEX dose appeared to be as
      effective as a 0.5 mg kg(-1) dose to reduce the incidence of PONV.

PMID- 22879657
TI  - Sugammadex and the cannot intubate/cannot ventilate scenario in patients with
      predicted difficult airway (1). Letter 1.

PMID- 22879658
TI  - Sugammadex and the cannot intubate/cannot ventilate scenario in patients with
      predicted difficult airway (1). Letter 2.

PMID- 22879659
TI  - Sugammadex and the cannot intubate/cannot ventilate scenario in patients with
      predicted difficult airway (1). Letter 3.

PMID- 22879661
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy and pancuronium.

PMID- 22879663
TI  - Seizures associated with local anaesthetic intoxication.

PMID- 22879665
TI  - Future of robotic anaesthesia.

PMID- 22879667
TI  - Hallucinations associated with cerebrospinal fluid leakage after a lumbar
      puncture.

PMID- 22879669
TI  - Failure of esmolol to control tachycardia associated with thyroid storm after
      subtotal thyroidectomy.

PMID- 22879670
TI  - Rotational vertigo and nystagmus rapidly after an intrathecal block with
      bupivacaine and fentanyl.

PMID- 22879671
TI  - Uvular trauma from a laryngeal mask.

PMID- 22879676
TI  - Influence of increased left ventricular myocardial mass on early and late
      mortality after cardiac surgery.
AB  - BACKGROUND: Increased left ventricular mass (LVM) is a well-recognized predictor
      of cardiovascular morbidity and mortality in epidemiological studies, but its
      impact on mortality after cardiac surgery is poorly defined. We hypothesized that
      patients with increased LVM index (LVMI) were more likely to have greater 30 day
      and 1 yr mortality. METHODS: With IRB approval, intraoperative transoesophageal
      echocardiography images of 844 cardiac surgical patients were reviewed. LVMI was
      calculated using the American Society of Echocardiography recommended formula.
      Outcome variables studied were 30 day and 1 yr mortality. RESULTS: Mortality
      within 30 days occurred in 28 patients (3.3%) and within 1 yr in 91 patients
      (10.8%). An almost linear relationship was found between increasing LVMI and the
      risk of mortality within 30 days of cardiac surgery. The odds ratio (OR) of dying
      within 30 days of surgery was 1.15 (95% confidence interval 1.01-1.31) per 20 g
      m(-2) increase in LVMI. This finding remained statistically significant in
      multivariate analysis controlling for the effects of age, weight, gender, surgery
      type, LV function, and functional status [OR=1.36 (1.11-1.66) per 20 g m(-2)
      increase]. Increased LVMI was not found to be a statistically significant
      predictor of 1 yr mortality. CONCLUSIONS: Increased LVMI, but not LV systolic
      function as measured by the fractional area of contraction (FAC) was identified
      as a strong independent predictor of perioperative mortality after adult cardiac
      surgery. The relationship between LVMI and risk of 30 day mortality was nearly
      linear. Furthermore, decreased FAC, and not LVMI, was a strong independent
      predictor of 1 yr mortality.

PMID- 22879677
TI  - Deltoid, triceps, or both responses improve the success rate of the interscalene
      catheter surgical block compared with the biceps response.
AB  - BACKGROUND: The influence of the muscular response elicited by neurostimulation
      on the success rate of interscalene block using a catheter (ISC) is unknown. In
      this investigation, we compared the success rate of ISC placement as indicated by
      biceps or deltoid, triceps, or both twitches. METHODS: Three hundred (ASA I-II)
      patients presenting for elective arthroscopic rotator cuff repair were
      prospectively randomized to assessment by biceps (Group B) or deltoid, triceps,
      or both twitches (Group DT). All ISCs were placed with the aid of
      neurostimulation. The tip of the stimulating needle was placed after
      disappearance of either biceps or deltoid, triceps, or both twitches at 0.3 mA.
      The catheter was advanced 2-3 cm past the tip of the needle and the block was
      performed using 40 ml ropivacaine 0.5%. Successful block was defined as sensory
      block of the supraclavicular nerve and sensory and motor block involving the
      axillary, radial, median, and musculocutaneous nerves within 30 min. RESULTS:
      Success rate was 98.6% in Group DT compared with 92.5% in Group B (95% confidence
      interval 0.01-0.11; P<0.02). Supplemental analgesics during handling of the
      posterior part of the shoulder capsule were needed in two patients in Group DT
      and seven patients in Group B. Three patients in Group B had an incomplete radial
      nerve distribution anaesthesia necessitating general anaesthesia. One patient in
      Group B had an incomplete posterior block extension of the supraclavicular nerve.
      No acute or late complications were observed. CONCLUSIONS: Eliciting deltoid,
      triceps, or both twitches was associated with a higher success rate compared with
      eliciting biceps twitches during continuous interscalene block.

PMID- 22879678
TI  - Neighborhood Effects in Temporal Perspective.
AB  - Theory suggests that neighborhood effects depend not only on where individuals
      live today, but also on where they lived in the past. Previous research, however,
      usually measured neighborhood context only once and did not account for length of
      residence, thereby understating the detrimental effects of long-term neighborhood
      disadvantage. This study investigates the effects of duration of exposure to
      disadvantaged neighborhoods on high school graduation. It follows 4,154 children
      in the PSID, measuring neighborhood context once per year from age 1 to 17. The
      analysis overcomes the problem of dynamic neighborhood selection by adapting
      novel methods of causal inference for time-varying treatments. In contrast to
      previous analyses, these methods do not "control away" the effect of neighborhood
      context operating indirectly through time-varying characteristics of the family,
      and thus they capture the full impact of a lifetime of neighborhood disadvantage.
      We find that sustained exposure to disadvantaged neighborhoods has a severe
      impact on high school graduation that is considerably larger than effects
      reported in prior research. Growing up in the most (compared to the least)
      disadvantaged quintile of neighborhoods is estimated to reduce the probability of
      graduation from 96% to 76% for black children, and from 95% to 87% for nonblack
      children.

PMID- 22879679
TI  - THE TRUE IDENTITY OF COPELAND'S AQUATIC SCUTTLE FLY (DIPTERA: PHORIDAE) FROM
      INDIANA AND RECOGNITION OF A SIBLING SPECIES FROM TEXAS.
AB  - Among the insects reported by Copeland (1989) breeding in the waters retained by
      treeholes in Indiana was a scuttle fly identified by W. H. Robinson as Megaselia
      scalaris (Loew). It is here reported that in fact this fly, along with fresh
      material from Illinois and Missouri, is M. imitatrix Borgmeier, whose type series
      was from Puerto Rico. An aquatic species reported from Texas is recognized as a
      sibling species of M. imitatrix and is named M. hansonix Disney, sp. nov. A
      single female from Brazil represents a third species of this complex, thus
      raising doubts about the identity of specimens from Brazil attributed to M.
      imitatrix by Benton and Claugher (2000).

PMID- 22879680
TI  - Cost-effective age structure and geographical distribution of boreal forest
      reserves.
AB  - 1. Forest reserves are established to preserve biodiversity, and to maintain
      natural functions and processes. Today there is heightened focus on old-growth
      stages, with less attention given to early successional stages. The biodiversity
      potential of younger forests has been overlooked, and the cost-effectiveness of
      incorporating different age classes in reserve networks has not yet been
      studied.2. We performed a reserve selection analysis in boreal Sweden using the
      Swedish National Forest Inventory plots. Seventeen structural variables were used
      as biodiversity indicators, and the cost of protecting each plot as a reserve was
      assessed using the Heureka system. A goal programming approach was applied, which
      allowed inclusion of several objectives and avoided a situation in which common
      indicators affected the result more than rare ones. The model was limited either
      by budget or area.3. All biodiversity indicators were found in all age classes,
      with more than half having the highest values in ages >= 100 years. Several large
      tree indicators and all deadwood indicators had higher values in forests 0-14
      years than in forests 15-69 years.4. It was most cost-effective to protect a
      large proportion of young forests since they generally have a lower net present
      value compared to older forests, but still contain structures of importance for
      biodiversity. However, it was more area-effective to protect a large proportion
      of old forests since they have a higher biodiversity potential per area.5. The
      geographical distribution of reserves selected with the budget-constrained model
      was strongly biassed towards the north-western section of boreal Sweden, with a
      large proportion of young forest, whereas the area-constrained model focussed on
      the south-eastern section, with dominance by the oldest age class.6.Synthesis and
      applications. We show that young forests with large amounts of structures
      important to biodiversity such as dead wood and remnant trees are cheap and cost
      efficient to protect. This suggests that reserve networks should incorporate
      sites with high habitat quality of different forest ages. Since young forests are
      generally neglected in conservation, our approach is of interest also to other
      forest biomes where biodiversity is adapted to disturbance regimes resulting in
      open, early successional stages.

PMID- 22879681
TI  - Exploring the role of environmental variables in shaping patterns of seabed
      biodiversity composition in regional-scale ecosystems.
AB  - 1. Environmental variables are often used as indirect surrogates for mapping
      biodiversity because species survey data are scant at regional scales, especially
      in the marine realm. However, environmental variables are measured on arbitrary
      scales unlikely to have simple, direct relationships with biological patterns.
      Instead, biodiversity may respond nonlinearly and to interactions between
      environmental variables.2. To investigate the role of the environment in driving
      patterns of biodiversity composition in large marine regions, we collated
      multiple biological survey and environmental data sets from tropical NE
      Australia, the deep Gulf of Mexico and the temperate Gulf of Maine. We then
      quantified the shape and magnitude of multispecies responses along >30
      environmental gradients and the extent to which these variables predicted
      regional distributions. To do this, we applied a new statistical approach,
      Gradient Forest, an extension of Random Forest, capable of modelling nonlinear
      and threshold responses.3. The regional-scale environmental variables predicted
      an average of 13-35% (up to 50-85% for individual species) of the variation in
      species abundance distributions. Important predictors differed among regions and
      biota and included depth, salinity, temperature, sediment composition and current
      stress. The shapes of responses along gradients also differed and were nonlinear,
      often with thresholds indicative of step changes in composition. These differing
      regional responses were partly due to differing environmental indicators of
      bioregional boundaries and, given the results to date, may indicate limited scope
      for extrapolating bio-physical relationships beyond the region of source data
      sets.4.Synthesis and applications. Gradient Forest offers a new capability for
      exploring relationships between biodiversity and environmental gradients,
      generating new information on multispecies responses at a detail not available
      previously. Importantly, given the scarcity of data, Gradient Forest enables the
      combined use of information from disparate data sets. The gradient response
      curves provide biologically informed transformations of environmental layers to
      predict and map expected patterns of biodiversity composition that represent
      sampled composition better than uninformed variables. The approach can be applied
      to support marine spatial planning and management and has similar applicability
      in terrestrial realms.Gradient Forest offers a new capability for exploring
      relationships between biodiversity and environmental gradients, generating new
      information on multispecies responses at a detail not available previously.
      Importantly, given the scarcity of data, Gradient Forest enables the combined use
      of information from disparate data sets. The gradient response curves provide
      biologically informed transformations of environmental layers to predict and map
      expected patterns of biodiversity composition that represent sampled composition
      better than uninformed variables. The approach can be applied to support marine
      spatial planning and management and has similar applicability in terrestrial
      realms.

PMID- 22879682
TI  - Culture and Probability Judgment Accuracy: The Influence of Holistic Reasoning.
AB  - A well-established phenomenon in the judgment and decision-making tradition is
      the overconfidence one places in the amount of knowledge that one possesses.
      Overconfidence or probability judgment accuracy varies not only individually but
      also across cultures. However, research efforts to explain cross-cultural
      variations in the overconfidence phenomenon have seldom been made. In Study 1,
      the authors compared the probability judgment accuracy of U.S. Americans (N =
      108) and Mexican participants (N = 100). In Study 2, they experimentally primed
      culture by randomly assigning English/Spanish bilingual Mexican Americans (N =
      195) to response language. Results of both studies replicated the cross-cultural
      variation of probability judgment accuracy previously observed in other cultural
      groups. U.S. Americans displayed less overconfidence when compared to Mexicans.
      These results were then replicated in bilingual participants, when culture was
      experimentally manipulated with language priming. Holistic reasoning did not
      account for the cross-cultural variation of overconfidence. Suggestions for
      future studies are discussed.

PMID- 22879683
TI  - Rethinking the Cultural Context of Schooling Decisions in Disadvantaged
      Neighborhoods: From Deviant Subculture to Cultural Heterogeneity.
AB  - The literature on neighborhood effects on schooling theorizes that neighborhood
      cultural context is an important mechanism generating such effects. However,
      explanations that rely on subcultural theories, such as oppositional culture,
      have met with considerable criticism on empirical grounds, and no alternative
      account of the cultural context of disadvantaged neighborhoods has been developed
      in the education literature. This study develops a new account of the cultural
      context of schooling decisions in disadvantaged neighborhoods based on the
      concept of cultural heterogeneity, defined as the presence of a wide array of
      competing and conflicting cultural models. It applies this concept to
      neighborhood effects on college enrollment. Using survey data from the National
      Longitudinal Study of Adolescent Health, this study shows that disadvantaged
      neighborhoods exhibit greater heterogeneity in college goals and that adolescents
      in more heterogeneous neighborhoods are less likely to act in concert with the
      college goals that they articulate.

PMID- 22879684
TI  - Synthetic studies toward (+)-cortistatin A.
AB  - We describe herein the synthesis of a late-stage intermediate en route to
      cortistatin A. Key transformations included a Snieckus-like cascade sequence
      culminating in a 6pi-electrocyclization, an alkylative dearomatization, and the
      stereoselective functionalization of the cortistatin A-ring. While the total
      synthesis we sought was not accomplished, the work sets the stage for several
      approaches to the preparation of novel analogs via diverted total synthesis.

PMID- 22879685
TI  - GENDER DIFFERENCES IN RISK/PROTECTION PROFILES FOR LOW ACADEMIC PERFORMANCE.
AB  - Using holistic-interactionistic theory, the simultaneous nature of risk and
      protection factors for both males and females (age 6-11 in Wave 1) is examined
      using Latent Profile Analysis (LPA). Risk/protection classes are estimated using
      multiple risk factor variables (e.g., physical child abuse) and multiple
      protective factors (e.g., extracurricular activities). These risk/protection
      classes were used to predict low academic performance. For both males and
      females, high risk, low protection individuals were significantly more likely to
      experience low academic performance than low risk, high protection cases. Gender
      differences emerged in a class for females that included the importance of
      parental/peer disapproval of anti-social behavior as a protective factor that was
      not present for males. Findings support elements of the holistic-interactionistic
      theory for human development and suggest the need to examine risk and protective
      factors in combination to account for their shared influences on developmental
      outcomes. Implications for youths underperforming academically are discussed.

PMID- 22879686
TI  - Evaluating the Evidence for the General Factor of Personality across Multiple
      Inventories.
AB  - A general factor of personality (GFP) has been proposed as the apex of a
      personality trait hierarchy that explains covariance among the lower-order
      factors measured by various personality inventories. In this study we evaluated
      the GFP hypothesis across several personality inventories, unlike most previous
      research in which the GFP has been derived from individual instruments in
      isolation. Exploratory analyses did not produce substantial evidence for the
      existence of a single cross-instrument higher-order factor of factors and efforts
      to specify a range of GFP-inspired models in a confirmatory framework led to
      significant estimation difficulties and poor fit to the data. Overall these
      results fail to support a common GFP that is positioned at the top of a
      personality trait hierarchy.

PMID- 22879687
TI  - The role of the North Atlantic Oscillation in controlling U.K. butterfly
      population size and phenology.
AB  - 1. The North Atlantic Oscillation (NAO) exerts considerable control on U.K.
      weather. This study investigates the impact of the NAO on butterfly abundance and
      phenology using 34 years of data from the U.K. Butterfly Monitoring Scheme
      (UKBMS).2. The study uses a multi-species indicator to show that the NAO does not
      affect overall U.K. butterfly population size. However, the abundance of
      bivoltine butterfly species, which have longer flight seasons, were found to be
      more likely to respond positively to the NAO compared with univoltine species,
      which show little or a negative response.3. A positive winter NAO index is
      associated with warmer weather and earlier flight dates for Anthocharis
      cardamines (Lepidoptera: Pieridae), Melanargia galathea (Lepidoptera:
      Nymphalidae), Aphantopus hyperantus (Lepidoptera: Nymphalidae), Pyronia tithonus
      (Lepidoptera: Nymphalidae), Lasiommata megera (Lepidoptera: Nymphalidae) and
      Polyommatus icarus (Lepidoptera: Lycaenidae). In bivoltine species, the NAO
      affects the phenology of the first generation, the timing of which indirectly
      controls the timing of the second generation.4. The NAO influences the timing of
      U.K. butterfly flight seasons more strongly than it influences population size.

PMID- 22879688
TI  - Novel Perfluorinated Polymer-Based Pervaporation Membranes for Separation of
      Solvent/Water Mixtures.
AB  - Traditionally, the pervaporation of water-solvent mixtures where the solvent is
      the major component is performed using hydrophilic membranes (such as PVA or
      zeolites). In the present paper a new type of pervaporation membrane (amorphous
      perfluorinated polymer, hydrophobic) was studied for separation of water-solvent
      mixtures. This membrane has high free volume and is inert for all solvents, and
      has a remarkable mechanical, chemical and thermal stability. The water is
      transported by solution diffusion model and the separation of solvent is
      primarily based on molecular sieving (size exclusion) principles. The membrane
      shows a high stability for operation over a broad range of feed concentrations
      without swelling; the operating temperature does not have a significant effect on
      membrane separation performance. Separation factors as high as 349 and 500 for
      water-ethanol and water-IPA mixtures (2-98 % wt water-solvent) and fluxes of 0.15
      and 0.05 kg/m(2)h, respectively were obtained at 22  degrees C. The permeance
      based selectivities were also calculated, and the selectivity is approximately
      constant for a wide range of feed concentrations. The pervaporation of more
      complex (ternary) mixtures of water-ethanol-ethyl acetate showed that this system
      could be successfully applied for solute separation based on size exclusion.

PMID- 22879689
TI  - The Relationship between Substance Abuse Performance Measures and Mutual Help
      Group Participation after Treatment.
AB  - We examined the relationship between treatment quality, using during-treatment
      process measures, and mutual help group (e.g., Alcoholics Anonymous) attendance
      after outpatient substance use disorder (SUD) treatment for 739 clients in the
      Alcohol and Drug Services Study. Logistic regression models estimated any and
      regular mutual help attendance after treatment. Clients referred to mutual help
      groups were significantly more likely to attend any mutual help after treatment.
      Results were mixed for facility offered mutual help groups; treatment engagement
      and retention were not significant. These findings offer treatment providers
      further evidence of the importance of referring clients to post-treatment mutual
      help groups, an effective, low-cost option.

PMID- 22879690
TI  - Microwave-assisted one-pot synthesis of water-soluble rare-earth doped fluoride
      luminescent nanoparticles with tunable colors.
AB  - Polyethyleneimine (PEI) functionalized multicolor luminescent LaF(3)
      nanoparticles were synthesized via a novel microwave-assisted method, which can
      achieve fast and uniform heating under eco-friendly and energy efficient
      conditions. The as-prepared nanoparticles possess a pure hexagonal structure with
      an average size of about 12 nm. When doped with different ions (Tb(3+) and
      Eu(3+)), the morphology and structure of the nanoparticles were not changed,
      whereas the optical properties varied with doped ions and their molar ratio, and
      as a result emission of four different colors (green, yellow, orange and red)
      were achieved by simply switching the types of doping ions (Eu(3+) versus Tb(3)
      +) and the molar ratio of the two doping ions.

PMID- 22879691
TI  - Low vision: we can all do more.

PMID- 22879692
TI  - Understanding low vision.

PMID- 22879693
TI  - Low vision: the patient's perspective.

PMID- 22879694
TI  - When someone has low vision.

PMID- 22879695
TI  - Making life easier for people with low vision.

PMID- 22879696
TI  - How to make an eye clinic more accessible for people with low vision.

PMID- 22879697
TI  - Low vision care: who can help?

PMID- 22879698
TI  - Improving access to low vision services.

PMID- 22879699
TI  - Low vision services for children in Tanzania.

PMID- 22879701
TI  - From our readers.

PMID- 22879700
TI  - An integrated low vision service: Sri Lanka.

PMID- 22879702
TI  - Trachoma: the beginning of the end?

PMID- 22879703
TI  - Picture quiz: non-optical measures to support children with low vision.

PMID- 22879704
TI  - Stochastic population forecasts based on conditional expert opinions.
AB  - The paper develops and applies an expert-based stochastic population forecasting
      method, which can also be used to obtain a probabilistic version of scenario
      based official forecasts. The full probability distribution of population
      forecasts is specified by starting from expert opinions on the future development
      of demographic components. Expert opinions are elicited as conditional on the
      realization of scenarios, in a two-step (or multiple-step) fashion. The method is
      applied to develop a stochastic forecast for the Italian population, starting
      from official scenarios from the Italian National Statistical Office.

PMID- 22879705
TI  - Making predictions from complex longitudinal data, with application to planning
      monitoring intervals in a national screening programme.
AB  - When biological or physiological variables change over time, we are often
      interested in making predictions either of future measurements or of the time
      taken to reach some threshold value. On the basis of longitudinal data for
      multiple individuals, we develop Bayesian hierarchical models for making these
      predictions together with their associated uncertainty. Particular aspects
      addressed, which include some novel components, are handling curvature in
      individuals' trends over time, making predictions for both underlying and
      measured levels, making predictions from a single baseline measurement, making
      predictions from a series of measurements, allowing flexibility in the error and
      random-effects distributions, and including covariates. In the context of data on
      the expansion of abdominal aortic aneurysms over time, where reaching a certain
      threshold leads to referral for surgery, we discuss the practical application of
      these models to the planning of monitoring intervals in a national screening
      programme. Prediction of the time to reach a threshold was too imprecise to be
      practically useful, and we focus instead on limiting the probability of exceeding
      the threshold after given time intervals. Although more complex models can be
      shown to fit the data better, we find that relatively simple models seem to be
      adequate for planning monitoring intervals.

PMID- 22879706
TI  - Characteristics of androgenetic alopecia in asian.
AB  - Androgenetic alopecia (AGA), or pattern hair loss, is a common disorder in Asian
      men and women, with a reported incidence of up to 73% among general population.
      There are several descriptions regarding the characteristics of AGA in patients
      of European descent. Asian patients with AGA have different types of hair loss
      and family histories from Europeans, which may affect treatment response.
      Therefore, in this review, prevalence, hair loss patterns, familial factors,
      androgen receptor gene polymorphisms of Asian AGA patients, and management based
      on algorithmic guidelines for AGA are discussed. This review may be useful for
      dermatologists in clinical practice for diagnosing and designing management
      approaches for Asian patients with AGA.

PMID- 22879707
TI  - Long term treatment concepts and proactive therapy for atopic eczema.
AB  - Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic,
      chronic skin disease, which is typically running in flares. The traditional
      treatment mainly consists of the reactive application of topical anti
      inflammatory agents such as topical corticosteroids and topical calcineurin
      inhibitors. The short term benefit of this approach is well known, but long term
      remission between flares is difficult to achieve. Therefore, innovative long-term
      treatment strategies targeting flare prevention and skin barrier stabilization
      are needed. We and others have shown that normal looking, non-lesional skin of
      atopic dermatitis patients is immunobiologially not normal but characterized by
      an invisible inflammation and barrier defect. This has led to the novel concept
      of proactive therapy, which is defined as long-term, low-dose intermittent
      application of anti-inflammatory therapy to the previously affected skin,
      together with an ongoing emollient treatment of unaffected skin. This review
      article describes the most important long-term treatment options for atopic
      dermatitis, which includes emollient therapy, the novel concept of proactive
      treatment, the different ultraviolet light modalities and a selection of systemic
      immunosuppressive drugs and biologics. Current trial data, licensed indications,
      off-label use and relevant side effects of the different treatment modalities are
      summarized.

PMID- 22879708
TI  - Epigenetic Modulation of Gene Expression during Keratinocyte Differentiation.
AB  - BACKGROUND: Epigenetic modulation of gene expression occurs by various methods,
      including DNA methylation and histone modification. DNA methylation of specific
      genes may affect the chromatin structure, preventing access by the
      transcriptional machinery. Although gene expression is dramatically changed
      during keratinocyte differentiation, there is no evidence of epigenetic
      modulation during the process of epidermal stratification. OBJECTIVE: We
      investigated whether epigenetic modulation is involved in keratinocyte
      differentiation-specific gene regulation. METHODS: We used trypsin to produce
      epidermal fragmentation (named T1-T4) and performed a morphological analysis
      using hematoxylin-eosin stain and cytokeratin expression based on reverse
      transcription polymerase chain reaction. We then constructed a DNA methylation
      microarray. RESULTS: Each epidermal fragment showed morphological features of the
      epithelial layer. T1 represented the basal layer, T2 was the spinous layer, T3
      was the granular layer, and T4 was the cornified layer. The level of the K14
      proliferation marker was increased in the T1 fraction, and the level of K10
      differentiation marker was increased in the T2-T4 fractions. Using a methylation
      microarray with the T1 and T4 fractions, we obtained many hypermethylated and
      hypomethylated genes from differentiated keratinocytes. CONCLUSION: The
      importance of epigenetic modulation in target gene expression during keratinocyte
      differentiation is identified.

PMID- 22879709
TI  - Intense Pulsed Light and Low-Fluence Q-Switched Nd:YAG Laser Treatment in Melasma
      Patients.
AB  - BACKGROUND: Recently, low fluence collimated Q-switched (QS) Nd:YAG laser has
      drawn attention for the treatment of melasma. However, it needs a lot of
      treatment sessions for the substantial results and repetitive laser exposures may
      end up with unwanted depigmentation. OBJECTIVE: We evaluated the clinical effects
      and safety of the combinational treatment, using intense pulsed light (IPL) and
      low fluence QS Nd:YAG laser. METHODS: Retrospective case series of 20 female
      patients, with mixed type melasma, were analyzed using medical records. They were
      treated with IPL one time, and 4 times of weekly successive low fluence Nd:YAG
      laser treatments. At each visit, digital photographs were taken under the same
      condition. Melanin index (MI) and erythema index (EI) were measured on the
      highest point on the cheekbones. Modified melasma area and severity index (MASI)
      scores were calculated by two investigators using digital photographs. RESULTS:
      The mean values of MI and EI decreased significantly after treatments. The
      modified MASI score has decreased by 59.35%, on average. Sixty percents of the
      participants did not require any more treatments, and no clinical aggravations
      were observed during the follow-up period (mean 5.9 months). CONCLUSION: IPL and
      low fluence laser may elicit a clinical resolution in the mixed type melasma with
      long term benefits.

PMID- 22879710
TI  - A survey of the awareness, knowledge and behavior of hair dye use in a korean
      population with gray hair.
AB  - BACKGROUND: Gray hair naturally develops in the process of human aging. Many
      people with gray hair periodically dye their hair. Hair dyeing products are
      widely used and they can cause adverse effects. Therefore, the user's knowledge
      and recognition about hair dyeing and related side effects are important.
      OBJECTIVE: The goal of this study was to lay the foundation for understanding,
      preventing and treating side effects caused by hair coloring products. METHODS:
      We conducted a questionnaire survey for adult males and females aged over 20 who
      had gray hair. A total of 500 subjects were included in this study and
      statistical analysis was performed. RESULTS: Large numbers of the people who had
      experience with hair dye (233 out of 319 people, 73.0%) did not know about the
      exact brand name of the hair dye product that they were using. Of 319 hair dye
      users, 23.8% (76 out of 319) people stated that they experienced side effects.
      Despite the occurrence of side effects from hair dyeing products, it seems they
      did not realize the seriousness of the side effects or the need for treatment.
      CONCLUSION: It is advisable to introduce a system that enables users to become
      aware of the ingredients and side effects of hair coloring products and give
      opportunities for users to become aware of the side effects of hair coloring
      through education, publicity and publication of an informational booklet.

PMID- 22879711
TI  - An open-label, split-face trial evaluating efficacy and safty of photopneumatic
      therapy for the treatment of acne.
AB  - BACKGROUND: Acne vulgaris is the most common skin disease worldwide, with many
      available treatment modalities, including oral and topical medications and laser
      therapy. Recently, a novel device (Isolaz, Pleasanton, CA, USA) that combines
      vacuum pressure and a broadband light source (400 nm to 1,200 nm) was developed
      for the treatment of acne. OBJECTIVE: To determine the clinical efficacy and
      safety of photopneumatic therapy for the treatment of acne vulgaris of the face.
      METHODS: Twenty adults with mild to moderate facial acne vulgaris received 4
      successive treatments on one side of the face with a combined photopneumatic
      device (intense pulsed light: fluence=5.8 J/cm(2); negative pressure=iMP mode) at
      2 week intervals. Acne lesions on the opposite side of the face were not treated.
      Lesion counts were performed at baseline, prior to each treatment session, and at
      3 months after the final treatment session. RESULTS: Significant lesion
      improvements and reduced numbers of acne lesions were observed on the treated
      side of the faces. Most patients experienced global clinical improvement. No
      severe side effects occurred during the study, with only a few patients
      experiencing transient erythema, purpura and/or exacerbation of pre-existing
      acne. CONCLUSION: Photopneumatic therapy is a safe and effective treatment for
      mild to moderate acne vulgaris.

PMID- 22879712
TI  - Molecular phylogenetics of exophiala species isolated from Korea.
AB  - BACKGROUND: Recently, identification of fungi have been supplemented by molecular
      tools, such as ribosomal internal transcribed spacer (ITS) sequence analysis.
      According to these tools, morphological Exophiala species was newly introduced or
      redefined. OBJECTIVE: This study was designed to investigate the phylogenetics
      based on ribosomal ITS sequence analysis from clinical Exophiala species isolated
      in Korea. METHODS: The strains of Exophiala species were 4 clinical isolates of
      phaeohyphomycosis agents kept in the department of dermatology, Dongguk
      University Medical Center(DUMC), Gyeongju, Korea. The DNAs of total 5 strains of
      Exophiala species were extracted by bead-beating method. Polymerase chain
      reaction of ITS region using the primer pairs ITS1-ITS4, was done and
      phylogenetic tree contributed from sequences of ITS region from 5 Korean isolates
      including E. dermatitidis CBS 109154 and comparative related strains deposited in
      GenBank. RESULTS: The strains of Exophiala species were 3 strains of E.
      dermatitidis, 1 strain of E. jeanselmei and 1 strain of Exophiala new species.
      Among the 3 subtypes (type A, B, C) of E. jeanselmei, E. jeanselmei DUMC 9901
      belonged to type B. Of the 2 main types of E. dermatitidis (type A, B) and 3
      subtypes of E. dermatitidis type A (A0, A1 and A2), two strains (E. dermatitidis
      CBS 709.95, E. dermatitidis CBS 109154) belonged to A0 subtypes, 1 strain (E.
      dermatitidis DUMC 9902) A1 subtype, respectively. CONCLUSION: Phylogenetic
      analysis of ITS region sequence provided useful information not only for new
      species identification but for the subtyping and origin of Exophiala species.

PMID- 22879713
TI  - The Efficacy and Safety of 17alpha-Estradiol (Ell-Cranell(r) alpha 0.025%)
      Solution on Female Pattern Hair Loss: Single Center, Open-Label, Non-Comparative,
      Phase IV Study.
AB  - BACKGROUND: There are several commercially available agents to treat female
      pattern hair loss (FPHL), including minoxidil solution, anti-androgen agents and
      mineral supplements. However, these treatments are not always satisfactory. We
      report the results of a clinical trial of 17alpha-estradiol (Ell-Cranell(r) alpha
      0.025%) solution to Korean female patients with FPHL. OBJECTIVE: This study was
      designed to examine the efficacy and safety of Ell-Cranell(r) alpha 0.025%
      solution in Korean female patients with FPHL. METHODS: A total of 53 women, 18 to
      55 years old, applied topical Ell-Cranell(r) alpha 0.025% solution once daily for
      8 months. Efficacy was evaluated by the change of hair counts and diameter,
      subjective assessment, and photographic assessment by investigators. RESULTS:
      Hair counts and diameter from baseline to 4 and 8 months after treatment
      increased in treated patients and these changes were statistically significant
      (p<0.0001). 17alpha-estradiol (Ell-Cranell(r) alpha 0.025%) solution showed
      significant improvement by subjective self-assessment and by investigator
      photographic assessment. Ell-Cranell(r) alpha 0.025% solution was well tolerated
      over 8-months period. CONCLUSION: This study showed that Ell-Cranell(r) alpha
      0.025% solution is a safe and effective agent for Korean women with FPHL.

PMID- 22879714
TI  - Clinical experience in the treatment of port-wine stains with blebs.
AB  - BACKGROUND: The current modality of choice for the treatment of Port-wine stains
      (PWS) is laser photocoagulation. Laser therapy for the treatment of PWS,
      especially with a pulsed dye laser (PDL), has been proven safe and effective;
      however, because penetration of the PDL is too shallow for an effective ablation
      of the blebs, treatment of blebbed PWS, using PDL, may be insufficient.
      OBJECTIVE: We demonstrated the clinical efficacy of a 1,064 nm long pulsed Nd:YAG
      laser with contact cooling device for blebbed PWS. METHODS: Twenty one patients
      with blebbed PWS (Fitzpatrick skin types II-V) underwent a treatment, using a
      1,064 nm long pulsed Nd:YAG laser with a contact cooling device at 8-week
      intervals. Treatments were done using 5~6 mm spot sizes at 20~30 ms and 95~170
      J/cm(2). Laser parameters were adjusted in order to meet the needs of each
      individual patient's lesions. RESULTS: All subjects tolerated the treatments
      well, and showed clinical improvement from blebs. Of the 21 patients, 18 of them
      experienced either moderate or excellent response. CONCLUSION: Use of a 1,064 nm
      long pulsed Nd:YAG laser results in a greater depth of vascular coagulation. A
      1,064 nm long pulsed Nd:YAG laser with contact cooling device may be regarded as
      a promising therapeutic option for the treatment of blebbed PWS.

PMID- 22879715
TI  - Quality of life assessment in male patients with androgenetic alopecia: result of
      a prospective, multicenter study.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is a common hair loss disease with
      genetic predisposition among men and women, and it may commence at any age after
      puberty. It may significantly affect a variety of psychological and social
      aspects of one's life and the individual's overall quality of life (QoL).
      OBJECTIVE: This study aimed to investigate the QoL of AGA patients and discover
      the factors that can influence the QoL of AGA patients, including previous
      experience in non-medical hair care, reasons for hospital visits, age, duration,
      and the severity of AGA. METHODS: A total of 998 male patients with AGA were
      interviewed, using the Hair Specific Skindex-29 to evaluate the QoL of AGA
      patients. RESULTS: The results of the Hair Specific Skindex-29 on patients with
      AGA were as follows: symptom scale: 26.3+/-19.5, function scale: 24.0+/-20.1,
      emotion scale: 32.1+/-21.8, and global score: 27.3+/-19.1. According to this
      assessment, QoL was more damaged if the patient had severe alopecia, a longer
      duration of AGA, younger age, had received previous non-medical hair care, and
      visited the hospital for AGA treatment. CONCLUSION: This study showed that AGA
      could harmfully affect the patients' QoL. These findings indicate that
      dermatologists should address these QoL issues when treating patients with
      alopecia.

PMID- 22879716
TI  - Clinical Features of Systemic Contact Dermatitis Due to the Ingestion of Lacquer
      in the Province of Chungcheongnam-do.
AB  - BACKGROUND: Lacquer contains an allergen, which can cause severe contact
      dermatitis. Systemic dermatitis resulting from the ingestion of lacquer is quite
      common in Korea, until now. OBJECTIVE: The purpose of this study is to elucidate
      the clinical features and laboratory findings of systemic contact dermatitis
      (SCD), due to the ingestion of lacquer in Chungcheongnam-do. METHODS: We
      retrospectively reviewed the medical records of 33 patients with SCD, after
      ingestion of lacquer from Soonchunhyang University Hospital in Cheonan, over a 6
      month period. RESULTS: In this study, 33.3% of patients ate lacquer, as a health
      food, and some (15.2%) by encouragement of friends or spouse. The most common way
      of ingestion was the lacquer-boiled chicken (48.5%), but many also ate lacquer
      tree sprouts (42.4%). The skin lesions developed as erythematous maculopapular
      eruptions, erythema multiforme, erythroderma, purpura, wheals and vesicles. On
      laboratory findings, 13 patients (52%) exhibited leukocytosis and 11 patients had
      elevated eosinophil counts. CONCLUSION: The general public is becoming more aware
      of the toxic effects of lacquer ingestion, but still does not fully understand
      the dangers of lacquer tree sprouts, and this ignorance is frequently causing SCD
      in Chungcheongnam-do.

PMID- 22879717
TI  - Effect of Spa Spring Water on Cytokine Expression in Human Keratinocyte HaCaT
      Cells and on Differentiation of CD4(+) T Cells.
AB  - BACKGROUND: Skin acts as the first line of defense against any foreign materials
      outside of our body. In inflammatory skin disease, the pathogenesis is due to an
      immune reaction in the keratinocytes, immune cells and soluble mediators.
      Balneotherapy is widely used for the treatment of inflammatory skin disease, but
      the mechanisms are only partly understood by immune regulation. Balneotherapy in
      dermatologic disease can affect the secretion of pro-inflammatory cytokines, IL
      1alpha and tumor necrosis factor from keratinocytes, and possibly affect the T
      cell differentiation. OBJECTIVE: In this study, we evaluated the effect of spa
      spring water from Yong-gung oncheon on the cells, and investigated the skin
      immune reaction. METHODS: We investigated the immunomodulatory or anti
      inflammatory effect of thermal spring water on the expression of pro-inflammatory
      cytokines in the HaCaT cells under Toll-like receptor (TLR) stimulation, as well
      as the effect on the differentiation of CD4(+) T cells under spring water.
      RESULTS: The treatment of spa spring water from Yong-gung oncheon decreased the
      expression of proinflammatory cytokines under TLR stimulation to the HaCaT cells
      and antigen presenting cells. In addition, spa spring water attenuated the
      differentiation process of subsets of CD4(+) T cells, i.e., Th1, Th2 and Th17
      cells. All these immune parameters can be used to evaluate the efficacy of spa
      spring water in Korea, in terms of the immune modulatory effect. CONCLUSION: Spa
      spring water treatment suppressed the inflammatory cytokines production and also
      modulated the differentiation of CD4(+) T cells into Th1, Th2, and Th17 cells,
      but not the T(regs) cells.

PMID- 22879718
TI  - Cardiac myxoma diagnosed by signs of purpuric macules on both palms and soles.
AB  - Cardiac myxoma, the most prevalent primary cardiac tumor, is rare. The clinical
      features of this tumor are principally intracardiac obstruction, extracardiac
      embolism, and general symptoms including fever, myalgia, arthralgia. Although
      cutaneous manifestations in patients with cardiac myxoma are frequent, in rare
      cases, cutaneous signs have been clues to the correct diagnosis. We report a 42
      year-old male who presented with recurrent multiple purpuric patches on both
      palms and soles for 4 months. Histopathological finding showed a myxomatous
      embolus in the arteriole in the lower dermis. Echocardiogram demonstrated the
      presence of a left atrial myxoma with a provisional diagnosis of left atrial
      myxoma. In our patient, skin examinations and histopathological finding led us to
      the diagnosis of cardiac myxoma.

PMID- 22879719
TI  - Successful treatment of alopecia areata with topical calcipotriol.
AB  - Alopecia areata (AA) is an inflammatory hair loss of unknown etiology. AA is
      chronic and relapsing, and no effective cure or preventive treatment has been
      established. Vitamin D was recently reported to be important in cutaneous immune
      modulation as well as calcium regulation and bone metabolism. It is well known
      that areata is common clinical finding in patients with vitamin D deficiency,
      vitamin D-resistant rickets, or vitamin D receptor (VDR) mutation. The biological
      actions of vitamin D3 derivatives include regulation of epidermal cell
      proliferation and differentiation and modulation of cytokine production. These
      effects might explain the efficacy of vitamin D3 derivatives for treating AA. In
      this study, we report a 7-year-old boy with reduced VDR expression in AA,
      recovery of whom was observed by topical application of calcipotriol, a strong
      vitamin D analog.

PMID- 22879720
TI  - Pityriasis versicolor on penile shaft in a renal transplant recipient.
AB  - Pityriasis versicolor is a superficial infection of the stratum corneum, which is
      caused by the Malassezia species. Tge Malassezia species consist of 12
      subspecies, including M. furfur, M. pachydermatis, M. symphodialis and M.
      globasa. The Malassezia species are classified as a normal flora, particularly in
      the sebum rich areas of the skin, and they convert from saprophytic yeast to
      parasitic mycelial morpholgic form to cause clinical disease. But majorities of
      their distributions are in the upper back, the neck, the thighs, and the forearm,
      and not in the penis. It is well known that the renal transplant patients, who
      take immunosuppressive agents, have impairment in the protective cell mediated
      immunity. Thus, they are more susceptible to infectious diseases, such as a
      fungal infection. Therefore, clinical manifestations show higher incidence of
      disease, but they mostly occur in an expected distribution. We here report a case
      of pityriasis versicolor in a renal transplant recipient on penile shaft, which
      is an unusual area.

PMID- 22879721
TI  - Type B pigmentary demarcation lines of pregnancy involving the anterior thighs
      and knees.
AB  - Pigmentary demarcation lines are abrupt transition lines between the areas of
      deeper pigmentation and the areas of lighter, normal pigmentation. Type B
      pigmentary demarcation lines involve the posterior medial portion of the lower
      extremities and are more commonly associated with pregnancy. We present a case of
      pigmentary demarcation lines of pregnancy with erythematous changes, involving
      both the anterior and posterior aspects of the lower extremities.

PMID- 22879722
TI  - Two cases of thrombosis of the palmar digital vein.
AB  - Palmar digital vein thrombosis causing one or more nodules seems to be a
      relatively rare condition, judging by the dearth of reports in the literature. It
      should always be considered in a patient who presents with a painful, firm, blue
      nodule located at or in close proximity to one of the flexion crease of the
      finger. Common lesions presenting as one or more solid digital nodules are
      ganglions, epidermal inclusion cysts, giant cell tumors, and lipomas. Thrombosis
      of the palmar digital veins should, however, be part of the differential
      diagnosis of palmar digital nodules because it is possible to manage it
      conservatively. We report two cases of thrombosis of palmar digital vein in a 33
      year-old woman and a 78-year-old man.

PMID- 22879723
TI  - Delayed Granulomatous Reaction after Oral Piercing during Thaipusam.

PMID- 22879724
TI  - A Rare Reason for Uvular Angioedema: Ecbalium elaterium.

PMID- 22879725
TI  - Pityriasis rosea-like rash secondary to intravesical bacillus calmette-guerin
      immunotherapy.

PMID- 22879726
TI  - Extensive pigmented purpuric dermatosis successfully treated with pentoxifylline.

PMID- 22879727
TI  - Figurate paraneoplastic urticaria and prostate cancer.

PMID- 22879728
TI  - Diagnosis of variant klinefelter syndrome in a 21-year-old male who presented
      with sparse facial hair.

PMID- 22879729
TI  - Efficacy of Finasteride 1.25 mg on Female Pattern Hair Loss; Pilot Study.

PMID- 22879730
TI  - Topical diphencyprone as an effective treatment for cutaneous metastatic
      melanoma.

PMID- 22879731
TI  - Erratum: Comment on "Pseudopautrier's Abscess".

PMID- 22879732
TI  - Successful treatment of xanthoma disseminatum with combined lipid lowering
      agents.

PMID- 22879733
TI  - Theoretical studies of a singlet oxygen-releasing dioxapaddlane (1,4-diicosa
      naphthalene-1,4-endoperoxide).
AB  - Theoretical calculations have been used to examine singlet oxygen release from a
      naphthalene endoperoxide which bears a flexible (CH(2))(22) polymethylene "lid".
      Monte Carlo and ONIOM calculations that incorporated semi-empirical and density
      functional theory predicted the conformational influence of the polymethylene
      chain in the cycloreversion of dioxapaddlane, 1,4-diicosa naphthalene-1,4
      endoperoxide, to (1)O(2) and 1,4-diicosa naphthalene. This study attempts to
      build a connection between (1)O(2) generation and "jump rope" dynamics of the
      dioxapaddlane. The polymethylene chain appears to function as a gatekeeper for
      the oxygen. Instead of coming full circle, a semi-circle rotation of the
      polymethylene bridge protected the peroxide group, limiting the dissociation of
      (1)O(2) from the naphthalene site.

PMID- 22879734
TI  - Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle
      glaucoma population.
AB  - PURPOSE: The aim of this study was to characterize a representative sample of the
      Peruvian population suffering open-angle glaucoma (OAG) with respect to the
      myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future
      glaucoma risk assessment. METHODS: DNA samples from 414 unrelated Peruvian
      subjects, including 205 open-angle glaucoma cases (10 juvenile glaucoma [JOAG],
      19 normal-tension glaucoma [NTG], and 176 POAG) and 209 randomly sampled
      controls, were screened for nucleotide changes in MYOC exon 3 by conformational
      sensitive gel electrophoresis (CSGE) and mutation screening. RESULTS: We
      identified a probable causative novel MYOC missense mutation, Gly326Ser, in one
      POAG case and found a consistent genotype-phenotype correlation in eight of his
      relatives. We also found the known causative MYOC mutation Trp286Arg in one JOAG
      case and one POAG case. A known causative single base MYOC deletion, T1357, was
      found in one POAG case. Two previously reported silent polymorphisms, Thr325Thr
      and Tyr347Tyr, were found in both the case and the control populations. A novel
      missense variant, Met476Arg, was identified in two unrelated controls.
      CONCLUSIONS: The screening of exon 3 of MYOC in a representative sample of 205
      independent POAG patients from Peru and 209 matched controls identified novel and
      previously reported mutations (both pathogenic and nonpathogenic) from other
      global regions. These results reflect the complex admixture of Amerindian and Old
      World ancestry in urban populations of Latin America, in general, and in Peru, in
      particular. It will be important to gather information about the ancestral origin
      of MYOC and other POAG gene mutations to develop screening panels and risk
      assessment for POAG in Peru.

PMID- 22879735
TI  - Protein kinase C activation affects, via the mRNA-binding Hu-antigen R/ELAV
      protein, vascular endothelial growth factor expression in a pericytic/endothelial
      coculture model.
AB  - PURPOSE: To explore whether, following direct contact, there is mutual influence
      between pericytes (PC) and endothelial cells (EC), and to establish whether
      protein kinase C (PKC) activation, a condition associated with hyperglycemia, can
      affect, via the mRNA-binding Hu-antigen R (HuR)/ELAV protein, the expression of
      vascular endothelial growth factor (VEGF). METHODS: PC and EC were cultured
      separately or in direct contact (1:1 ratio), and exposed or not to phorbol
      esters, a PKC activator (100 nM for 15 min). Barrier integrity was evaluated by
      measuring endothelial electrical resistance and permeability to sodium
      fluorescein. Immunocytochemistry was performed to visualize EC and PC in
      coculture, and to evaluate phorbol 12-myristate-13-acetate (PMA)-induced HuR
      translocation. PKCbetaI/betaII, HuR, and VEGF protein content was measured with
      western blotting, VEGF secretion in cell culture medium was evaluated with enzyme
      linked immunosorbent assay (ELISA), and quantification of VEGF mRNA was performed
      with real-time quantitative PCR. RESULTS: In monocultures, VEGF mRNA/protein
      basal levels were more elevated in PC than in EC. However, the basal expression
      of VEGF protein, but not mRNA, in PC and EC was affected by culture conditions.
      In fact, physical contact with PC upregulated VEGF protein levels in the EC,
      while VEGF was downregulated in PC cocultured with EC. In this last condition,
      PKCbetaII and HuR protein basal levels were also decreased in monocultured PC.
      Moreover, in basal conditions, the amount of VEGF released from the coculture was
      higher than from the monocultures. Direct activation of PKCbeta induced HuR
      translocation from the nuclear area to the cytoplasm, and increased the protein
      levels of the kinase itself, HuR, and VEGF in PC and EC in both culture
      conditions. Concerning VEGF mRNA, PKC activation induced an increase in PKC
      levels only in monocultured EC and, conversely, a significant decrease in the
      same transcript amount in cocultured PC. PMA stimulus also led to a significant
      increase in VEGF secretion in coculture. CONCLUSIONS: When cocultured with PC, EC
      form a significantly tighter barrier than the endothelial monolayer. The physical
      contact leads to opposite changes in VEGF protein levels in PC and EC. In
      particular, in basal conditions, cocultured PC seemed to downregulate their own
      expression of this proproliferating factor, as well as that of PKCbetaII and HuR,
      likely to maintain the 1:1 ratio with the cohabiting EC. In mono- and cocultured
      PC/EC, PKC direct activation led to a similar increase in PKCbetaI/betaII, HuR,
      and VEGF protein levels, changes that may also occur at early stages of diabetic
      retinopathy. The release of VEGF in the medium was favored by physical contact
      between PC and EC and was further increased by PMA exposure. In contrast with the
      effects on VEGF protein, PKCbeta activation induced modifications in VEGF mRNA
      content that are different in function of the cell type and the culture
      conditions. These findings suggest that the changes in the VEGF protein and
      transcript observed in PC/EC can be ascribed to distinct and concomitant
      pathways. Further studies on this in vitro coculture model would be useful to
      better understand the PC/EC interaction in physiologic and pathological
      conditions.

PMID- 22879736
TI  - Phase contrast microscopy of living cells within the whole lens: spatial
      correlations and morphological dynamics.
AB  - PURPOSE: Images from cultured lens cells do not convey enough spatial
      information, and imaging of fixed lens specimens cannot reveal dynamic changes in
      the cells. As such, a real-time, convenient approach for monitoring label-free
      imaging of dynamic processes of living cells within the whole lens is urgently
      needed. METHODS: Female Wistar rat lenses were kept in organ culture. Insulin
      like growth factor-I was added to the culture medium to induce cell mitosis. A
      novel method of ultraviolet (UV) irradiation was used to induce cell apoptosis
      and fiber damage. The cellular morphological dynamics within the whole lens were
      monitored by inverted phase contrast microscopy. Apoptosis was assessed using a
      commercial kit with Hoechst 33342/YO-PRO(r)-1/propidium iodide (PI). RESULTS: The
      intrinsic transparency and low-light scattering property of the rat lens
      permitted direct imaging of the lens epithelial cells (LECs) and the superficial
      fiber cells. We visualized the processes of mitosis and apoptosis of the LECs,
      and we obtained dynamic images of posterior fiber cells following UVA
      irradiation. CONCLUSIONS: This method opens a new window for observing lens cells
      in their physiologic location, and it can be readily applied in studies on lens
      physiology and pathology.

PMID- 22879737
TI  - Patient perspectives on the impact of Crohn's disease: results from group
      interviews.
AB  - AIM: To understand the impact of Crohn's disease (CD) on various aspects of daily
      life from the perspective of patients living with CD. Awareness of the disease
      and biologic therapies, patient satisfaction and adherence, and physician
      (provider) relationships were also assessed. BACKGROUND: CD is a chronic,
      inflammatory, autoimmune disorder of the gastrointestinal tract that
      substantially impacts patients' physical and emotional well-being. For patients
      eligible for biologic therapy, anti-tumor necrosis factor agents represent an
      important addition to the available therapies for CD. METHODS: The study sample
      included biologic-naive and biologic-experienced patients who had self-reported
      moderate to severe CD, were under the care of a specialist, and agreed to film a
      video diary and participate in a focus group. Data from the videos and group
      interviews were collected from May to June of 2009 and summarized qualitatively
      by grouping similar answers and quotations. RESULTS: Of the 44 participants who
      submitted video diaries, 23 were biologic-experienced and 21 were biologic-naive.
      Participants stated that CD caused fear and embarrassment, that they were
      reluctant to share the full impact of CD with family and providers, and that they
      relied on their provider for treatment decisions. Many participants accepted a
      new state of normalcy if their current medication helped their most bothersome
      symptoms without providing sustained remission. Participants receiving biologic
      therapy generally were more informed, more satisfied, and more likely to adhere
      to treatment regimens. CONCLUSION: Participants' responses suggest a need for
      more patient education and more collaborative relationships between patients and
      providers (physicians) regarding treatment decisions.

PMID- 22879738
TI  - Validation of a patient interview for assessing reasons for antipsychotic
      discontinuation and continuation.
AB  - INTRODUCTION: The Reasons for Antipsychotic Discontinuation Interview (RAD-I) was
      developed to assess patients' perceptions of reasons for discontinuing or
      continuing an antipsychotic. The current study examined reliability and validity
      of domain scores representing three factors contributing to these treatment
      decisions: treatment benefits, adverse events, and distal reasons other than
      direct effects of the medication. METHODS: Data were collected from patients with
      schizophrenia or schizoaffective disorder and their treating clinicians. For
      approximately 25% of patients, a second rater completed the RAD-I for assessment
      of inter-rater reliability. RESULTS: All patients (n = 121; 81 discontinuation,
      40 continuation) reported at least one reason for discontinuation or continuation
      (mean = 2.8 reasons for discontinuation; 3.4 for continuation). Inter-rater
      reliability was supported (kappas = 0.63-1.0). Validity of the discontinuation
      domain scores was supported by associations with symptom measures (the Positive
      and Negative Syndrome Scale for Schizophrenia, the Clinical Global Impression -
      Schizophrenia Scale; r = 0.30 to 0.51; all P < 0.01), patients' primary reasons
      for discontinuation, and adverse events. However, the continuation domain scores
      were not significantly associated with these other indicators. DISCUSSION:
      Results support the reliability, convergent validity, and known-groups validity
      of the RAD-I for assessing patients' reasons for antipsychotic discontinuation.
      Further research is needed to examine validity of the RAD-I continuation section.

PMID- 22879739
TI  - Paliperidone palmitate injection for the acute and maintenance treatment of
      schizophrenia in adults.
AB  - PURPOSE: To review the use of paliperidone palmitate in treatment of patients
      with schizophrenia. METHODS: Published clinical trial data for the development
      and utilization of paliperidone palmitate for the treatment of schizophrenia were
      assessed in this review. Four short-term, randomized, double-blind, placebo
      controlled trials investigated the efficacy of paliperidone palmitate in acute
      exacerbation of schizophrenia. Paliperidone palmitate was also studied as a
      maintenance treatment to prevent or delay relapse in stable schizophrenia. In
      addition, paliperidone palmitate was compared to risperidone long-acting
      injection for noninferiority in three studies. RESULTS: Paliperidone palmitate
      has been shown to be effective in reducing symptoms as measured by the Positive
      and Negative Syndrome Scale total scores in the four acute treatment studies. In
      the maintenance treatment studies, paliperidone palmitate was found to be more
      effective than placebo in preventing or delaying the time to first relapse in
      stable schizophrenia patients. In addition, paliperidone palmitate was shown to
      be noninferior to risperidone long-acting injection in two studies. It was shown
      to be reasonably well tolerated in all clinical trials. Acute treatment phase
      should be initiated with a dose of 234 mg on day one and 156 mg on day eight,
      followed by a recommended monthly maintenance dose of 39-234 mg based on efficacy
      and tolerability results from the clinical studies. CONCLUSION: Providing an
      optimal long-term treatment can be challenging. Paliperidone palmitate can be
      used as an acute treatment even in outpatient setting, and it has shown to be
      well tolerated by patients. Also, it does not require overlapping oral
      antipsychotic supplementation while being initiated, and is dosed once per month.

PMID- 22879740
TI  - Facet-sparing lumbar decompression with a minimally invasive flexible MicroBlade
      Shaver(r) versus traditional decompression: quantitative radiographic assessment.
AB  - BACKGROUND: Laminectomy/laminotomy and foraminotomy are well established surgical
      techniques for treatment of symptomatic lumbar spinal stenosis. However, these
      procedures have significant limitations, including limited access to lateral and
      foraminal compression and postoperative instability. The purpose of this cadaver
      study was to compare bone, ligament, and soft tissue morphology following lumbar
      decompression using a minimally invasive MicroBlade Shaver(r) instrument versus
      hemilaminotomy with foraminotomy (HL). METHODS: The iO-Flex(r) system utilizes a
      flexible over-the-wire MicroBlade Shaver instrument designed for facet-sparing,
      minimally invasive "inside-out" decompression of the lumbar spine. Unilateral
      decompression was performed at 36 levels in nine human cadaver specimens, six
      with age-appropriate degenerative changes and three with radiographically
      confirmed multilevel stenosis. The iO-Flex system was utilized on alternating
      sides from L2/3 to L5/S1, and HL was performed on the opposite side at each level
      by the same investigator. Spinal canal, facet joint, lateral recess, and
      foraminal morphology were assessed using computed tomography. RESULTS: Similar
      increases in soft tissue canal area and decreases in ligamentum flavum area were
      noted in nondiseased specimens, although HL required removal of 83% more laminar
      area (P < 0.01) and 95% more bone resection, including the pars interarticularis
      and facet joints (P < 0.001), compared with the iO-Flex system. Similar increases
      in lateral recess diameter were noted in nondiseased specimens using each
      procedure. In stenotic specimens, the increase in lateral recess diameter was
      significantly (P = 0.02) greater following use of the iO-Flex system (43%) versus
      HL (7%). The iO-Flex system resulted in greater facet joint preservation in
      nondiseased and stenotic specimens. In stenotic specimens, the iO-Flex system
      resulted in a significantly greater increase in foraminal width compared with HL
      (24% versus 4%, P = 0.01), with facet joint preservation. CONCLUSION: The iO-Flex
      system resulted in significantly better decompression of the lateral recess and
      foraminal areas compared with HL, while preserving posterior spinal elements,
      including the facet joint.

PMID- 22879741
TI  - Cellular phone-based image acquisition and quantitative ratiometric method for
      detecting cocaine and benzoylecgonine for biological and forensic applications.
AB  - Here we describe the first report of using low-cost cellular or web-based digital
      cameras to image and quantify standardized rapid immunoassay strips as a new
      point-of-care diagnostic and forensics tool with health applications.
      Quantitative ratiometric pixel density analysis (QRPDA) is an automated method
      requiring end-users to utilize inexpensive (~ $1 USD/each) immunotest strips, a
      commonly available web or mobile phone camera or scanner, and internet or
      cellular service. A model is described whereby a central computer server and
      freely available IMAGEJ image analysis software records and analyzes the incoming
      image data with time-stamp and geo-tag information and performs the QRPDA using
      custom JAVA based macros (http://www.neurocloud.org). To demonstrate QRPDA we
      developed a standardized method using rapid immunotest strips directed against
      cocaine and its major metabolite, benzoylecgonine. Images from standardized
      samples were acquired using several devices, including a mobile phone camera, web
      cam, and scanner. We performed image analysis of three brands of commercially
      available dye-conjugated anti-cocaine/benzoylecgonine (COC/BE) antibody test
      strips in response to three different series of cocaine concentrations ranging
      from 0.1 to 300 ng/ml and BE concentrations ranging from 0.003 to 0.1 ng/ml. This
      data was then used to create standard curves to allow quantification of COC/BE in
      biological samples. Across all devices, QRPDA quantification of COC and BE proved
      to be a sensitive, economical, and faster alternative to more costly methods,
      such as gas chromatography-mass spectrometry, tandem mass spectrometry, or high
      pressure liquid chromatography. The limit of detection was determined to be
      between 0.1 and 5 ng/ml. To simulate conditions in the field, QRPDA was found to
      be robust under a variety of image acquisition and testing conditions that varied
      temperature, lighting, resolution, magnification and concentrations of biological
      fluid in a sample. To determine the effectiveness of the QRPDA method for
      quantifying cocaine in biological samples, mice were injected with a sub
      locomotor activating dose of cocaine (5 mg/kg; i.p.) and were found to have
      detectable levels of COC/BE in their urine (160.6 ng/ml) and blood plasma (8.1
      ng/ml) after 15-30 minutes. By comparison rats self-administering cocaine in a 4
      hour session obtained a final BE blood plasma level of 910 ng/ml with an average
      of 62.5 infusions. It is concluded that automated QRPDA is a low-cost, rapid and
      highly sensitive method for the detection of COC/BE with health, forensics, and
      bioinformatics application and the potential to be used with other rapid
      immunotest strips directed at several other targets. Thus, this report serves as
      a general reference and method describing the use of image analysis of lateral
      flow rapid test strips.

PMID- 22879742
TI  - Avoiding DWI Among Bar-room Drinkers: Strategies and Predictors.
AB  - We examined the prevalence and predictors of 11strategies to avoid driving when
      feeling intoxicated among 561 bar-room patrons in two medium-sized Maryland
      communities. Logistic regression analyses identified demographic, behavioral, and
      attitudinal predictors of avoidance strategies and interactions among predictors.
      Overall, 89% reported one or more DWI avoidance actions in the past year, and 38%
      reported driving intoxicated during that time. Average frequencies of avoidance
      behavior and intoxicated driving increased significantly as drinking level
      increased. However, the higher the drinking level, the smaller the ratio of
      avoidance actions to DWI experiences, highlighting the vulnerability of heavy
      drinkers who had driven intoxicated.Using a sober driver or one who allegedly
      drank less than the respondent were the most popular and frequent strategies, but
      paying for a cab, walking, and using a bus or free cab were relatively unpopular.
      Higher drinking levels predicted significantly higher odds of using avoidance
      approaches, as did intoxicated driving. Confidence in driving safely when
      intoxicated was positively related to drinking level and intoxicated driving, but
      it tended to predict lower odds of avoidance actions. Similarly, marital status,
      age, gender, and location influenced the odds of avoidance behaviors.
      Interventions should be strategically tailored to exploit or counter drinker
      predilections among avoidance options.

PMID- 22879743
TI  - Imagery scripts and a computerized subtraction stress task both induce stress in
      methamphetamine users: a controlled laboratory study.
AB  - Patients treated for methamphetamine (MA) dependence have a high rate of relapse,
      and stress is thought to play a key role. We sought to develop a computerized
      procedure for experimentally inducing stress in MA users. In a within-subjects
      design, we compared a computerized subtraction stress task (SST) to personalized
      stress-imagery scripts and a control condition (neutral imagery) in 9 former MA
      users, recruited in San Francisco in 2006-2007. We assessed blood hormone levels,
      anxiety and craving for MA on visual analog scales, and the Positive and Negative
      Affect Schedule and made linear mixed-effects models to analyze the results. Both
      the SST and stress scripts were effective in inducing self-report markers of
      stress in MA users. Because the SST is easily reproducible and requires less time
      of staff and participants, it may be a useful alternative for measuring stress
      reactivity in drug users.

PMID- 22879744
TI  - Effect of potassium channel modulators on morphine withdrawal in mice.
AB  - The present study was conducted to investigate the effect of potassium channel
      openers and blockers on morphine withdrawal syndrome. Mice were rendered
      dependent on morphine by subcutaneous injection of morphine; four hours later,
      withdrawal was induced by using an opioid antagonist, naloxone. Mice were
      observed for 30 minutes for the withdrawal signs ie, the characteristic jumping,
      hyperactivity, urination and diarrhea. ATP-dependent potassium (K(+) (ATP))
      channel modulators were injected intraperitoneally (i.p.) 30 minutes before the
      naloxone. It was found that a K(+) (ATP) channel opener, minoxidil (12.5-50 mg/kg
      i.p.), suppressed the morphine withdrawal significantly. On the other hand, the
      K(+) (ATP) channel blocker glibenclamide (12.5-50 mg/kg i.p.) caused a
      significant facilitation of the withdrawal. Glibenclamide was also found to
      abolish the minoxidil's inhibitory effect on morphine withdrawal. The study
      concludes that K(+) (ATP) channels play an important role in the genesis of
      morphine withdrawal and K(+) (ATP) channel openers could be useful in the
      management of opioid withdrawal. As morphine opens K(+) (ATP) channels in
      neurons, the channel openers possibly act by mimicking the effects of morphine on
      neuronal K(+) currents.

PMID- 22879745
TI  - Long-acting injectable naltrexone for the management of patients with opioid
      dependence.
AB  - Opioid dependence is a condition with serious clinical ramifications. Treatment
      has focused on detoxification, agonist therapy with methadone or buprenorphine,
      or remission maintenance with the opioid antagonist, naltrexone. Treatment with
      oral naltrexone has been limited by poor treatment adherence and relapse. Studies
      with long-acting formulations have shown increased treatment adherence. Extended
      release injectable naltrexone has been used for the treatment of alcohol
      dependence, and has recently received an indication for treatment of opioid
      dependence from the US Food and Drug Administration. Dosing occurs once monthly
      and existing data with long-acting naltrexone supports efficacy of treatment for
      opioid dependence; however published data is sparse. Treatment with long-acting
      naltrexone should be monitored for hepatotoxicity, and patients should be made
      aware of increased risk of overdose with administration of opioids during and
      immediately after discontinuation of long-acting naltrexone.

PMID- 22879746
TI  - Potential for tramadol abuse by patients visiting pharmacies in northern iran.
AB  - BACKGROUND: It has been almost three decades since tramadol was introduced to the
      market as a centrally acting analgesic. It is claimed to have weak opioid
      properties and a low dependence potential in opioid-addicted patients. This study
      was designed to investigate the suspicion of potential tramadol abuse among
      patients visiting pharmacies in Babol, one of the major cities in northern Iran.
      METHODS: Under supervision by pharmacists, a questionnaire designed to monitor
      drug abuse was filled out for every patient who requested tramadol from Babol's
      pharmacies during 6 months (Aug. 2007 till Feb. 2008). The data obtained were
      used to derive descriptive statistics and to make a comparison with results from
      other countries. RESULTS: Of 162 patients (or someone on their behalf) who had
      sought tramadol from a pharmacy, 92 (56%) patients did not have a prescription.
      At least 103 (64%) patients reported criteria for addiction (ie, for feeling of
      psychological well being, unable to cease taking the drug, more than two weeks of
      tramadol use). In total, 145 (89%) patients were aged younger than 30 years, and
      90 (55%) patients were aged younger than 18 years. More than 63% of patients
      reported a history of addiction or drug abuse. Most of the patients with no
      prescription (88%) had abuse/addiction criteria. CONCLUSION: Patients who request
      tramadol from pharmacies in Babol seem to have a high potential for drug abuse,
      in particular those who do not have prescriptions. The high prevalence of people
      under 18 years of age seeking tramadol could be a worldwide trend. We recommend
      further governmental support for pharmacies to deal with tramadol abusers in
      northern Iran.

PMID- 22879747
TI  - Illicit opioid intoxication: diagnosis and treatment.
AB  - Opioid intoxications and overdose are associated with high rates of morbidity and
      mortality. Opioid overdose may occur in the setting of intravenous or intranasal
      heroin use, illicit use of diverted opioid medications, intentional or accidental
      misuse of prescription pain medications, or iatrogenic overdose. In this review,
      we focused on the epidemiology of illict opioid use in the United States and on
      the mechanism of action of opioid drugs. We also described the signs and
      symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the
      reader about the most recent recommendations for treatment and prevention of
      opioid intoxications and overdose.

PMID- 22879748
TI  - What works for patients in outpatient treatment for alcohol addiction? An
      explorative study into clients' evaluation of subjective factors and therapy
      satisfaction.
AB  - This explorative survey investigated clients' evaluation of therapy elements and
      other supportive factors within a randomized controlled trial. The treatment of
      patients with alcohol dependence consisted of pharmacotherapy
      (acamprosate/naltrexone/placebo) and biweekly medical management (MM). Forty-nine
      study participants were surveyed with a questionnaire to measure both the
      patients' satisfaction with the therapy and the subjective assessment of
      treatment elements and supportive factors.Study participants were highly
      satisfied with the treatment. The supportive factors previously identified by
      Orford et al1 were confirmed. 'Pharmacotherapy' was rated significantly less
      effective than 'MM' and 'global study attendance' (P < 0.001). The significant
      differences in the evaluation of treatment elements point to a preference for
      regular low-key contacts rather than for medication. Such contacts based on MM
      could be a useful intervention in clinical care, and its effectivity should be
      examined more closely in further research.

PMID- 22879749
TI  - Validation of a targeted peer relations scale for adolescents treated for
      substance use disorder: an application of rasch modeling.
AB  - The objective of this research is to use item response theory (IRT) to validate a
      14-item peer relations scale for use in the adolescent treatment population.
      Subjects are 509 adolescents discharged from substance abuse treatment from 2004
      2009. The person reliability is 0.76 and the Cronbach's alpha person raw score
      reliability is 0.93 both indicating the scale is a strong metric. The item
      reliability of 0.99 is high showing the model is reliable. The real separation
      (8.49) meaning items are placed on the Rasch "ruler" with about eight levels of
      importance identified. The mean-square statistics of the infit and outfit values
      were between 0.5 and 1.5 for the items indicating a low level of randomness and
      thus unidimensionality of the scale. Inspection of a Wright Item Map shows the
      hierarchical structure of the scale with a moderate degree of inter-item spread.
      The analysis shows the scale is a reliable unidimensional metric.

PMID- 22879750
TI  - Using facebook to maximize follow-up response rates in a longitudinal study of
      adults who use methamphetamine.
AB  - This study examines the process and effects of using facebook (FB) to locate and
      re-contact study participants targeted for follow up in a longitudinal study of
      adult methamphetamine users (N = 649). A follow-up interview was conducted in
      2009-11 approximately 8 years after previous study participation. Our paper
      describes re-contact efforts involving FB, including IRB regulatory issues and
      the effectiveness of using FB compared to mailings and phone calls. A total of 48
      of the 551 surviving non-incarcerated participants who agreed to be contacted for
      follow up studies were contacted via FB, of whom 11 completed the follow-up
      interview. Those contacted through FB were more likely to be younger, female,
      relocated out-of-state, and reported somewhat higher rates of anxiety and
      cognitive problems compared to those not located on FB. Although participants
      contacted through FB are likely to differ demographically from those contacted by
      phone or mail, FB provides a potentially effective means to expand conventional
      methods of correspondence for contacting hard to reach participants.

PMID- 22879751
TI  - Drug, sex and age differentials in the use of Australian publicly funded
      treatment services.
AB  - CONTEXT: Little is known about the proportion of the Australian population using
      alcohol or other drugs who may seek treatment. There is a need to have some
      additional estimates of population morbidity which reflect harms associated with
      use. OBJECTIVE: To determine Australian population rates of publicly funded
      community based specialised alcohol and other drug treatment and in-patient
      hospital care by those 'at risk', by drug type, sex and age. DESIGN AND SETTING:
      The design is secondary data analysis of publicly available datasets. We use the
      latest available complete data on Australian general population incidence of
      alcohol, cannabis amphetamines and ecstasy use (2007 National Drug Strategy
      Household Survey) and nationally collected administrative data on publicly funded
      specialised alcohol and other drug treatment services (2006-2007 Alcohol and
      Other Drug Treatment Services National Minimum Dataset) and public hospitals
      (2006-2007 National Hospital Morbidity Minimum Dataset) to calculate rates of
      drug treatment and in-patient hospital care per 1000 Australians. 'At risk' for
      alcohol is defined as being at risk of short term harm, as defined by the
      National Health and Medical Research Council (2001). 'At risk' for illicit drugs
      is defined as those exposed to potential harm through at least weekly use of
      cannabis, amphetamines and ecstasy use. RESULTS: Risky alcohol consumption
      followed by recent cannabis use appears to lead to most harm. Greater harm seems
      to be experienced by males rather than females. Younger adults (15-19 years) and
      older adults (40+ years) seem also to experience the highest rates of harm.
      CONCLUSIONS: It is possible to derive population estimates of harms associated
      with licit and illicit drugs use. Treatment rates vary across drug type, gender
      and age. Alcohol and cannabis are the substances whose use leads to the greatest
      demand for services. Ecstasy appears to generate few presentations for treatment.
      Publicly available data can be used to estimate harms associated with the use of
      particular substances. Such estimates are best interpreted in the light of other
      ways of estimating harms.

PMID- 22879752
TI  - Researching Prescription Drug Misuse among First Nations in Canada: Starting from
      a Health Promotion Framework.
AB  - The intentional misuse of psychotropic drugs is recognized as a significant
      public health concern in Canada, although there is a lack of empirical research
      detailing this. Even less research has been documented on the misuse of
      prescription drugs among First Nations in Canada. In the past, Western biomedical
      and individual-based approaches to researching Indigenous health have been
      applied, whereas First Nations' understandings of health are founded on a
      holistic view of wellbeing. Recognition of this disjuncture, alongside the
      protective influence of First Nations traditional culture, is foundational to
      establishing an empirical understanding of and comprehensive response to
      prescription drug misuse. We propose health promotion as a framework from which
      to begin to explore this. Our work with a health promotion framework has conveyed
      its potential to support the consideration of Western and Indigenous worldviews
      together in an 'ethical space', with illustrations provided. Health promotion
      also allots for the consideration of Canada's colonial history of knowledge
      production in public health and supports First Nations' self-determination. Based
      on this, we recommend three immediate ways in which a health promotion framework
      can advance research on prescription drug misuse among First Nations in Canada.

PMID- 22879754
TI  - Bupropion reduces some of the symptoms of marihuana withdrawal in chronic
      marihuana users: a pilot study.
AB  - Bupropion's (Zyban((r)) SR) effectiveness to treat symptoms experienced in
      marihuana withdrawal was tested in a double-blind, placebo-controlled study with
      chronic, heavy marihuana users. Participants maintained their usual marihuana
      intake until Quit Day after which they were required to cease intake of THC
      products for 14 days. A Withdrawal Discomfort Score revealed that for 7 days
      immediately following cessation, placebo-treated subjects reported more symptoms
      than bupropion-treated subjects. Self-reported craving for marihuana increased
      for the placebo-treated group but not for those treated with bupropion. Measures
      of sleep and cognitive performance were not different between the two groups.
      Participants in the bupropion treatment arm were more likely to complete the
      study than those randomized to the placebo arm (50% completion for bupropion vs.
      33% completion for placebo). These results suggest that bupropion may be useful
      for alleviating marihuana withdrawal symptoms and be useful in subject retention
      during long-term cessation programs.

PMID- 22879753
TI  - Current and emerging directions in the treatment of eating disorders.
AB  - Eating disorders are a significant source of psychiatric morbidity in young women
      and demonstrate high comorbidity with mood, anxiety, and substance use disorders.
      Thus, clinicians may encounter eating disorders in the context of treating other
      conditions. This review summarizes the efficacy of current and emerging
      treatments for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating
      disorder (BED). Treatment trials were identified using electronic and manual
      searches and by reviewing abstracts from conference proceedings. Family based
      therapy has demonstrated superiority for adolescents with AN but no treatment has
      established superiority for adults. For BN, both 60 mg fluoxetine and cognitive
      behavioral therapy (CBT) have well-established efficacy. For BED, selective
      serotonin reuptake inhibitors, CBT, and interpersonal psychotherapy have
      demonstrated efficacy. Emerging directions for AN include investigation of the
      antipsychotic olanzapine and several novel psychosocial treatments. Future
      directions for BN and BED include increasing CBT disseminability, targeting
      affect regulation, and individualized stepped-care approaches.

PMID- 22879755
TI  - Monitoring Utilization of a Large Scale Addiction Treatment System: The Drug and
      Alcohol Treatment Information System (DATIS).
AB  - Client-based information systems can yield data to address issues of system
      accountability and planning, and contribute information related to changing
      patterns of substance use in treatment and, indirectly, general populations. The
      Drug and Alcohol Treatment Information System (DATIS) monitors the number/types
      of clients treated in approximately 170 publicly-funded addiction treatment
      agencies in Ontario. The purpose of this study was to estimate the caseload of
      addiction treatment agencies, and describe important characteristics of clients,
      their patterns of service utilization and trends over-time from 2005 to 2010. In
      2009-2010, 47,065 individuals were admitted to treatment. Since 2005-2006, there
      has been an increase in adolescents/youth in treatment, and a decrease in the
      male-female gender ratio. Alcohol problems predominated, but an increasing
      proportion of clients used cannabis and prescription opioids. DATIS is an
      evolving system and an integral component of Ontario's performance measurement
      system. Linkages with healthcare information systems will allow for longitudinal
      tracking of client health-related outcomes.

PMID- 22879756
TI  - Introductory editorial.

PMID- 22879757
TI  - A hybrid model for automatic emotion recognition in suicide notes.
AB  - We describe the Open University team's submission to the 2011 i2b2/VA/Cincinnati
      Medical Natural Language Processing Challenge, Track 2 Shared Task for sentiment
      analysis in suicide notes. This Shared Task focused on the development of
      automatic systems that identify, at the sentence level, affective text of 15
      specific emotions from suicide notes. We propose a hybrid model that incorporates
      a number of natural language processing techniques, including lexicon-based
      keyword spotting, CRF-based emotion cue identification, and machine learning
      based emotion classification. The results generated by different techniques are
      integrated using different vote-based merging strategies. The automated system
      performed well against the manually-annotated gold standard, and achieved
      encouraging results with a micro-averaged F-measure score of 61.39% in textual
      emotion recognition, which was ranked 1st place out of 24 participant teams in
      this challenge. The results demonstrate that effective emotion recognition by an
      automated system is possible when a large annotated corpus is available.

PMID- 22879758
TI  - Suicide note sentiment classification: a supervised approach augmented by web
      data.
AB  - OBJECTIVE: To create a sentiment classification system for the Fifth i2b2/VA
      Challenge Track 2, which can identify thirteen subjective categories and two
      objective categories. DESIGN: We developed a hybrid system using Support Vector
      Machine (SVM) classifiers with augmented training data from the Internet. Our
      system consists of three types of classification-based systems: the first system
      uses spanning n-gram features for subjective categories, the second one uses bag
      of-n-gram features for objective categories, and the third one uses pattern
      matching for infrequent or subtle emotion categories. The spanning n-gram
      features are selected by a feature selection algorithm that leverages emotional
      corpus from weblogs. Special normalization of objective sentences is generalized
      with shallow parsing and external web knowledge. We utilize three sources of web
      data: the weblog of LiveJournal which helps to improve the feature selection, the
      eBay List which assists in special normalization of information and instructions
      categories, and the suicide project web which provides unlabeled data with
      similar properties as suicide notes. MEASUREMENTS: The performance is evaluated
      by the overall micro-averaged precision, recall and F-measure. RESULT: Our system
      achieved an overall micro-averaged F-measure of 0.59. Happiness_peacefulness had
      the highest F-measure of 0.81. We were ranked as the second best out of 26
      competing teams. CONCLUSION: Our results indicated that classifying fine-grained
      sentiments at sentence level is a non-trivial task. It is effective to divide
      categories into different groups according to their semantic properties. In
      addition, our system performance benefits from external knowledge extracted from
      publically available web data of other purposes; performance can be further
      enhanced when more training data is available.

PMID- 22879759
TI  - A hybrid approach to sentiment sentence classification in suicide notes.
AB  - This paper describes the sentiment classification system developed by the Mayo
      Clinic team for the 2011 I2B2/VA/Cincinnati Natural Language Processing (NLP)
      Challenge. The sentiment classification task is to assign any pertinent emotion
      to each sentence in suicide notes. We have implemented three systems that have
      been trained on suicide notes provided by the I2B2 challenge organizer-a machine
      learning system, a rule-based system, and a system consisting of a combination of
      both. Our machine learning system was trained on re-annotated data in which
      apparently inconsistent emotion assignment was adjusted. Then, the machine
      learning methods by RIPPER and multinomial Naive Bayes classifiers, manual
      pattern matching rules, and the combination of the two systems were tested to
      determine the emotions within sentences. The combination of the machine learning
      and rule-based system performed best and produced a micro-average F-score of
      0.5640.

PMID- 22879760
TI  - Emotion Detection in Suicide Notes using Maximum Entropy Classification.
AB  - An ensemble of supervised maximum entropy classifiers can accurately detect and
      identify sentiments expressed in suicide notes. Using lexical and syntactic
      features extracted from a training set of externally annotated suicide notes, we
      trained separate classifiers for each of fifteen pre-specified emotions. This
      formed part of the 2011 i2b2 NLP Shared Task, Track 2. The precision and recall
      of these classifiers related strongly with the number of occurrences of each
      emotion in the training data. Evaluating on previously unseen test data, our best
      system achieved an F(1) score of 0.534.

PMID- 22879761
TI  - Fine-grained emotion detection in suicide notes: a thresholding approach to multi
      label classification.
AB  - We present a system to automatically identify emotion-carrying sentences in
      suicide notes and to detect the specific fine-grained emotion conveyed. With this
      system, we competed in Track 2 of the 2011 Medical NLP Challenge,14 where the
      task was to distinguish between fifteen emotion labels, from guilt, sorrow, and
      hopelessness to hopefulness and happiness.Since a sentence can be annotated with
      multiple emotions, we designed a thresholding approach that enables assigning
      multiple labels to a single instance. We rely on the probability estimates
      returned by an SVM classifier and experimentally set thresholds on these
      probabilities. Emotion labels are assigned only if their probability exceeds a
      certain threshold and if the probability of the sentence being emotion-free is
      low enough. We show the advantages of this thresholding approach by comparing it
      to a naive system that assigns only the most probable label to each test
      sentence, and to a system trained on emotion-carrying sentences only.

PMID- 22879762
TI  - LASSA: Emotion Detection via Information Fusion.
AB  - DUE TO THE COMPLEXITY OF EMOTIONS IN SUICIDE NOTES AND THE SUBTLE NATURE OF
      SENTIMENTS, THIS STUDY PROPOSES A FUSION APPROACH TO TACKLE THE CHALLENGE OF
      SENTIMENT CLASSIFICATION IN SUICIDE NOTES: leveraging WordNet-based lexicons,
      manually created rules, character-based n-grams, and other linguistic features.
      Although our results are not satisfying, some valuable lessons are learned and
      promising future directions are identified.

PMID- 22879763
TI  - Using ensemble models to classify the sentiment expressed in suicide notes.
AB  - In 2007, suicide was the tenth leading cause of death in the U.S. Given the
      significance of this problem, suicide was the focus of the 2011 Informatics for
      Integrating Biology and the Bedside (i2b2) Natural Language Processing (NLP)
      shared task competition (track two). Specifically, the challenge concentrated on
      sentiment analysis, predicting the presence or absence of 15 emotions (labels)
      simultaneously in a collection of suicide notes spanning over 70 years. Our team
      explored multiple approaches combining regular expression-based rules,
      statistical text mining (STM), and an approach that applies weights to text while
      accounting for multiple labels. Our best submission used an ensemble of both
      rules and STM models to achieve a micro-averaged F(1) score of 0.5023, slightly
      above the mean from the 26 teams that competed (0.4875).

PMID- 22879764
TI  - A naive bayes approach to classifying topics in suicide notes.
AB  - The authors present a system developed for the 2011 i2b2 Challenge on Sentiment
      Classification, whose aim was to automatically classify sentences in suicide
      notes using a scheme of 15 topics, mostly emotions. The system combines machine
      learning with a rule-based methodology. The features used to represent a problem
      were based on lexico-semantic properties of individual words in addition to
      regular expressions used to represent patterns of word usage across different
      topics. A naive Bayes classifier was trained using the features extracted from
      the training data consisting of 600 manually annotated suicide notes.
      Classification was then performed using the naive Bayes classifier as well as a
      set of pattern-matching rules. The classification performance was evaluated
      against a manually prepared gold standard consisting of 300 suicide notes, in
      which 1,091 out of a total of 2,037 sentences were associated with a total of
      1,272 annotations. The competing systems were ranked using the micro-averaged F
      measure as the primary evaluation metric. Our system achieved the F-measure of
      53% (with 55% precision and 52% recall), which was significantly better than the
      average performance of 48.75% achieved by the 26 participating teams.

PMID- 22879765
TI  - Labeling emotions in suicide notes: cost-sensitive learning with heterogeneous
      features.
AB  - This paper describes a system developed for Track 2 of the 2011 Medical NLP
      Challenge on identifying emotions in suicide notes. Our approach involves
      learning a collection of one-versus-all classifiers, each deciding whether or not
      a particular label should be assigned to a given sentence. We explore a variety
      of features types-syntactic, semantic and surface-oriented. Cost-sensitive
      learning is used for dealing with the issue of class imbalance in the data.

PMID- 22879766
TI  - A combined approach to emotion detection in suicide notes.
AB  - In this paper, we present the system we have developed for participating in the
      second task of the i2b2/VA 2011 challenge dedicated to emotion detection in
      clinical records. On the official evaluation, we ranked 6th out of 26
      participants. Our best configuration, based upon a combination of both a machine
      learning based approach and manually-defined transducers, obtained a 0.5383
      global F-measure, while the distribution of the other 26 participants' results is
      characterized by mean = 0.4875, stdev = 0.0742, min = 0.2967, max = 0.6139, and
      median = 0.5027. Combination of machine learning and transducer is achieved by
      computing the union of results from both approaches, each using a hierarchy of
      sentiment specific classifiers.

PMID- 22879767
TI  - Topic categorisation of statements in suicide notes with integrated rules and
      machine learning.
AB  - We describe and evaluate an automated approach used as part of the i2b2 2011
      challenge to identify and categorise statements in suicide notes into one of 15
      topics, including Love, Guilt, Thankfulness, Hopelessness and Instructions. The
      approach combines a set of lexico-syntactic rules with a set of models derived by
      machine learning from a training dataset. The machine learning models rely on
      named entities, lexical, lexico-semantic and presentation features, as well as
      the rules that are applicable to a given statement. On a testing set of 300
      suicide notes, the approach showed the overall best micro F-measure of up to
      53.36%. The best precision achieved was 67.17% when only rules are used, whereas
      best recall of 50.57% was with integrated rules and machine learning. While some
      topics (eg, Sorrow, Anger, Blame) prove challenging, the performance for
      relatively frequent (eg, Love) and well-scoped categories (eg, Thankfulness) was
      comparatively higher (precision between 68% and 79%), suggesting that automated
      text mining approaches can be effective in topic categorisation of suicide notes.

PMID- 22879768
TI  - Combining Lexico-semantic Features for Emotion Classification in Suicide Notes.
AB  - This paper describes a system for automatic emotion classification, developed for
      the 2011 i2b2 Natural Language Processing Challenge, Track 2. The objective of
      the shared task was to label suicide notes with 15 relevant emotions on the
      sentence level. Our system uses 15 SVM models (one for each emotion) using the
      combination of features that was found to perform best on a given emotion.
      Features included lemmas and trigram bag of words, and information from semantic
      resources such as WordNet, SentiWordNet and subjectivity clues. The best
      performing system labeled 7 of the 15 emotions and achieved an F-score of 53.31%
      on the test data.

PMID- 22879769
TI  - Early fusion of low level features for emotion mining.
AB  - WE STUDY THE DISCRIMINATION OF EMOTIONS ANNOTATED IN FREE TEXTS AT THE SENTENCE
      LEVEL: a sentence can either be associated with no emotion (neutral) or multiple
      labels of emotion. The proposed system relies on three characteristics. We
      implement an early fusion of grams of increasing orders transposing an approach
      successfully employed in the related task of opinion mining. We apply a filtering
      process that consists in extracting frequent n-grams and making use of the
      Shannon's entropy measure to respectively maintain dictionaries at balanced sizes
      and keep emotion specific features. Finally the overall system is implemented as
      a 2-step decision process: a first classifier discriminates between neutral and
      emotion bearing sentences, then one classifier per emotion is applied on emotion
      bearing sentences. The final decision is given by the classifier holding the
      maximum confidence. Results obtained on the testing set are promising.

PMID- 22879770
TI  - Discovering Fine-grained Sentiment in Suicide Notes.
AB  - This paper presents our solution for the i2b2 sentiment classification challenge.
      Our hybrid system consists of machine learning and rule-based classifiers. For
      the machine learning classifier, we investigate a variety of lexical, syntactic
      and knowledge-based features, and show how much these features contribute to the
      performance of the classifier through experiments. For the rule-based classifier,
      we propose an algorithm to automatically extract effective syntactic and lexical
      patterns from training examples. The experimental results show that the rule
      based classifier outperforms the baseline machine learning classifier using
      unigram features. By combining the machine learning classifier and the rule-based
      classifier, the hybrid system gains a better trade-off between precision and
      recall, and yields the highest micro-averaged F-measure (0.5038), which is better
      than the mean (0.4875) and median (0.5027) micro-average F-measures among all
      participating teams.

PMID- 22879771
TI  - Binary classifiers and latent sequence models for emotion detection in suicide
      notes.
AB  - This paper describes the National Research Council of Canada's submission to the
      2011 i2b2 NLP challenge on the detection of emotions in suicide notes. In this
      task, each sentence of a suicide note is annotated with zero or more emotions,
      making it a multi-label sentence classification task. We employ two distinct
      large-margin models capable of handling multiple labels. The first uses one
      classifier per emotion, and is built to simplify label balance issues and to
      allow extremely fast development. This approach is very effective, scoring an F
      measure of 55.22 and placing fourth in the competition, making it the best system
      that does not use web-derived statistics or re-annotated training data. Second,
      we present a latent sequence model, which learns to segment the sentence into a
      number of emotion regions. This model is intended to gracefully handle sentences
      that convey multiple thoughts and emotions. Preliminary work with the latent
      sequence model shows promise, resulting in comparable performance using fewer
      features.

PMID- 22879772
TI  - Leveraging psycholinguistic resources and emotional sequence models for suicide
      note emotion annotation.
AB  - We describe the submission entered by SRI International and UC Davis for the I2B2
      NLP Challenge Track 2. Our system is based on a machine learning approach and
      employs a combination of lexical, syntactic, and psycholinguistic features. In
      addition, we model the sequence and locations of occurrence of emotions found in
      the notes. We discuss the effect of these features on the emotion annotation
      task, as well as the nature of the notes themselves. We also explore the use of
      bootstrapping to help account for what appeared to be annotator fatigue in the
      data. We conclude a discussion of future avenues for improving the approach for
      this task, and also discuss how annotations at the word span level may be more
      appropriate for this task than annotations at the sentence level.

PMID- 22879773
TI  - A hybrid system for emotion extraction from suicide notes.
AB  - The reasons that drive someone to commit suicide are complex and their study has
      attracted the attention of scientists in different domains. Analyzing this
      phenomenon could significantly improve the preventive efforts. In this paper we
      present a method for sentiment analysis of suicide notes submitted to the
      i2b2/VA/Cincinnati Shared Task 2011. In this task the sentences of 900 suicide
      notes were labeled with the possible emotions that they reflect. In order to
      label the sentence with emotions, we propose a hybrid approach which utilizes
      both rule based and machine learning techniques. To solve the multi class problem
      a rule-based engine and an SVM model is used for each category. A set of
      syntactic and semantic features are selected for each sentence to build the rules
      and train the classifier. The rules are generated manually based on a set of
      lexical and emotional clues. We propose a new approach to extract the sentence's
      clauses and constitutive grammatical elements and to use them in syntactic and
      semantic feature generation. The method utilizes a novel method to measure the
      polarity of the sentence based on the extracted grammatical elements, reaching
      precision of 41.79 with recall of 55.03 for an f-measure of 47.50. The overall
      mean f-measure of all submissions was 48.75% with a standard deviation of 7%.

PMID- 22879774
TI  - Three hybrid classifiers for the detection of emotions in suicide notes.
AB  - We describe our approach for creating a system able to detect emotions in suicide
      notes. Motivated by the sparse and imbalanced data as well as the complex
      annotation scheme, we have considered three hybrid approaches for distinguishing
      between the different categories. Each of the three approaches combines machine
      learning with manually derived rules, where the latter target very sparse emotion
      categories. The first approach considers the task as single label multi-class
      classification, where an SVM and a CRF classifier are trained to recognise
      fifteen different categories and their results are combined. Our second approach
      trains individual binary classifiers (SVM and CRF) for each of the fifteen
      sentence categories and returns the union of the classifiers as the final result.
      Finally, our third approach is a combination of binary and multi-class
      classifiers (SVM and CRF) trained on different subsets of the training data. We
      considered a number of different feature configurations. All three systems were
      tested on 300 unseen messages. Our second system had the best performance of the
      three, yielding an F1 score of 45.6% and a Precision of 60.1% whereas our best
      Recall (43.6%) was obtained using the third system.

PMID- 22879775
TI  - Rule-based and lightly supervised methods to predict emotions in suicide notes.
AB  - This paper describes the Duluth systems that participated in the Sentiment
      Analysis track of the i2b2/VA/Cincinnati Children's 2011 Challenge. The top
      Duluth system was a rule-based approach derived through manual corpus analysis
      and the use of measures of association to identify significant ngrams. This
      performed in the median range of systems, attaining an F-measure of 0.45. The
      second system was automatically derived from the most frequent bigrams unique to
      one or two emotions. It achieved an F-measure of 0.36. The third system was the
      union of the first two, and reached an F-measure of 0.44.

PMID- 22879776
TI  - Statistical and similarity methods for classifying emotion in suicide notes.
AB  - In this paper we report on the approaches that we developed for the 2011 i2b2
      Shared Task on Sentiment Analysis of Suicide Notes. We have cast the problem of
      detecting emotions in suicide notes as a supervised multi-label classification
      problem. Our classifiers use a variety of features based on (a) lexical
      indicators, (b) topic scores, and (c) similarity measures. Our best submission
      has a precision of 0.551, a recall of 0.485, and a F-measure of 0.516.

PMID- 22879777
TI  - Overexpression of human SOD1 improves survival of mice susceptible to endotoxic
      shock.
AB  - BACKGROUND: Protective effects of the antioxidant enzyme Cu-Zn superoxide
      dismutase (SOD1) against endotoxic shock have not been demonstrated in animal
      models. We used a murine model to investigate whether overexpression of SOD1
      protects against endotoxic shock, and whether the genetic background of SOD1
      affects its effective protective effects and susceptibility to endotoxic shock.
      METHODS: Transgenic (tg) mice overexpressing human SOD1 and control mice were
      divided into four groups based on their genetic background: (1) tg mice with
      mixed genetic background (tg-JAX); (2) wild-type (WT) littermates of tg-JAX
      strain (WT-JAX); (3) tg mice with C57BL/6J background (tg-TX); (4) WT littermates
      of tg-TX strain (WT-TX). Activity of SOD1 in the intestine, heart, and liver of
      tg and control mice was confirmed using a polyacrylamide activity gel. Endotoxic
      shock was induced by intraperitoneal injection of lipopolysaccharide. Survival
      rates over 120 hours (mean, 95% confidence interval) were analyzed using Kaplan
      Meier survival curves. RESULTS: Human SOD1 enzymatic activities were
      significantly higher in the intestine, heart, and liver of both tg strains (tg
      JAX and tg-TX) compared with their WT littermates (WT-JAX and WT-TX,
      respectively). Interestingly, the endogenous SOD1 activities in tg-JAX mice were
      decreased compared with their WT littermates (WT-JAX), but such aberrant changes
      were not observed in tg-TX mice. There was no difference in the survival time
      between tg-JAX and WT-JAX groups after endotoxic shock (P > 0.05). However, the
      survival time in the tg-TX group was more than twofold longer than that in the WT
      TX group (P < 0.05). In addition, WT-JAX mice survived significantly longer than
      WT-TX mice (P < 0.05). CONCLUSION: Aberrant decrease of endogenous SOD1
      activities may have overshadowed the effect of overexpression of SOD1 in tg mice
      (tg-JAX). Mice with C57BL/6J background (tg-TX) are more susceptible to
      lipopolysaccharide-induced endotoxic shock than those with mixed genetic
      background (tg-JAX). Overexpression of SOD1 is protective only in mice with
      C57BL/6J background (tg-TX).

PMID- 22879778
TI  - Alteration of complement hemolytic activity in different trauma and sepsis
      models.
AB  - Complement activation is involved in various diseases in which innate immunity
      plays a crucial role. However, its pathophysiological relevance is not clearly
      understood. Experimental models have been widely used to characterize the role of
      complement activation under different pathological conditions, such as hypoxemia,
      ischemia and reperfusion, tissue damage, and polymicrobial invasion. Screening of
      the complement status and function is, however, strongly dependent on the
      laboratory-specific techniques being used to sample and measure complement,
      making it difficult to compare the results found in different laboratories.
      Therefore, we evaluated complement function by measuring complement hemolytic
      activity (CH50) in various animal models of isolated ischemia reperfusion (I/R:
      kidney, liver, gut), hemorrhagic traumatic shock (HTS), endotoxic shock (LPS),
      and sepsis (CLP). Complement activation was less pronounced in isolated models of
      ischemia and reperfusion, whereas a strong complement response was observed early
      after HTS, CLP, and LPS. In summary, CH50 is a well-established, quick, and cost
      effective screening method of complement function. However, because we obtained
      different results in clinically relevant animal models, further differentiation
      using specific complement factor analysis is necessary.

PMID- 22879779
TI  - Nasal packing aspiration in a patient with Alzheimer's disease: a rare
      complication.
AB  - Nasal bleeding is a frequent problem for patients receiving anticoagulant agents.
      Most cases are successfully managed with anterior or posterior nasal packing.
      However, the complications of nasal packing should be always considered. We
      report the case of a 78-year-old man with Alzheimer's disease who was treated for
      anterior epistaxis with anterior nasal packing using three pieces of antibiotic
      soaked gauze. Two days later, the patient was admitted to the emergency
      department in respiratory distress. A chest x-ray demonstrated atelectasis of the
      right lung. During an examination of the nasal cavities, the nasal packing was
      removed, and one of the gauze pieces was missing. The patient underwent rigid
      bronchoscopy, and the missing gauze was found to be obstructing the right main
      bronchus. The patient's respiratory function improved considerably after removal
      of the foreign body. It is assumed that gauze packs should be used with caution
      in patients with an impaired level of consciousness and neurodegenerative
      diseases.

PMID- 22879780
TI  - Hypertrophic scarring in cleft lip repair: a comparison of incidence among ethnic
      groups.
AB  - BACKGROUND: Although hypertrophic scar (HTS) formation following cleft lip repair
      is relatively common, published rates vary widely, from 1% to nearly 50%. The
      risk factors associated with HTS formation in cleft patients are not well
      characterized. The primary aim of this retrospective study of 180 cleft lip
      repairs is to evaluate the frequency of postoperative HTS among various ethnic
      groups following cleft lip repair. METHODS: A retrospective chart view of
      patients undergoing primary cleft lip repair over a 16-year period (1990-2005) by
      the senior surgeon was performed. The primary outcome was the presence of HTS at
      1 year postoperatively. Bivariate analysis and multivariable logistic regression
      were used to evaluate potential risk factors for HTS, including ethnicity, type
      and laterality of cleft, and gender. RESULTS: One hundred and eighty patients who
      underwent cleft lip repair were included in the study. The overall rate of
      postoperative HTS formation was 25%. Ethnicity alone was found to be an
      independent predictor of HTS formation. Caucasian patients had the lowest rate of
      HTS formation (11.8%) and were used as the reference group. HTS rates were
      significantly higher in the other ethnicities, 32.2% in Hispanic patients (odds
      ratio [OR]: 3.51; 95% confidence interval [CI]: 1.53-8.85), and 36.3% for Asian
      patients (OR 4.27; 95% CI: 1.36-13.70). Sex, cleft type, and cleft laterality
      were not associated with increased rates of HTS. CONCLUSIONS: Differences in
      ethnic makeup of respective patient populations may be a major factor influencing
      the wide variability of reported HTS rates. Consideration should be given to
      potential prophylactic treatments for HTS in susceptible ethnic populations.

PMID- 22879781
TI  - A Pain-free Lancet with a Small Needle for Glucose Measurement.
AB  - A new lancet with an extremely small needle (0.15 mm diameter and 0.75 mm length)
      mounted on a small pedestal was tested in diabetic patients for blood glucose
      measurement in a randomized clinical study. A total of 37 diabetic patients were
      enrolled for the study. A pain scale categorized from 0 to 3 was created to
      measure the intensity of puncture pain which was explained to patients before
      testing. The patients' fingers were punctured with their own old style lancets at
      least 1 hour before the punctures by the new lancets, and puncture pains recorded
      according to the pain scale. All patients tested with the new lancet reported no
      pain and recorded the puncture pain as scale 0. Among the total 37 patients
      tested with their old style lancets, 2 patients (5.40%) reported no pain and
      recorded the pain as scale 0, thirteen patients (35.14%) recorded as scale 1, 16
      patients (43.24%) as scale 2, and 6 patients (16.22%) as scale 3. The average
      pain scale of the patients who used old style lancets was 1.702 with the standard
      error 0.133. The chi-square goodness-of-fit test shows that the proportion of the
      pain scales comes from the claimed distribution with unequal frequencies, and chi
      square tests for independence indicate that neither sex nor age of the sample
      patients is related to the pain scales.The paired t-test to test the existence of
      any difference in pain levels between the new lancet and the old style lancet
      showed; t = 1.702/0.133 = 12.796 with p-value < 0.005 (df = 36). The average pain
      level from the old style lancet is significantly higher than from the new
      lancets. Pain-free needle puncture was achieved by limiting the puncture depth to
      less than 0.75 mm with a thin needle with a 0.15 mm diameter. By allowing
      patients to see the new lancets before testing, psychological pain anticipation
      was minimized as the very thin and short needle is visually less intimidating.
      With a pain free puncture, better compliance and improved subsequent glucose
      levels may be achieved.

PMID- 22879782
TI  - Diurnal Variation in Peripheral (Hair) vs Central (Saliva) HPA Axis Cortisol
      Concentrations.
AB  - Cortisol concentrations in hair and saliva collected from male and female adults
      over a 15-hour period were compared for differences in overall level and cyclic
      pattern. Typical diurnal fluctuations were noted for both salivary and hair
      cortisol, with some individual differences that are congruent with the previous
      literature. Issues of the link between central and peripheral HPA axes are raised
      for discussion and further investigation, and hypothetical explanations for the
      diurnal variability shown in these two sets of cortisol secretion patterns are
      discussed from an evolutionary advantage perspective.

PMID- 22879783
TI  - An Investigation of Hair Cortisol Concentration Across Body Sites and within Hair
      Shaft.
AB  - Cortisol concentrations in hair collected from young male and female adults were
      assayed and compared for differences along shaft length and between body sites.
      No significant differences were found between hair shaft sites, supporting a
      model of the hair shaft as "alive" and responsive to environmental demand in
      terms of cortisol production. Hair taken from forearms had significantly higher
      concentrations of cortisol than hair from lower legs, suggesting a localized hair
      cortisol response and verifying previous findings. Issues of the link between
      central and peripheral HPA axes are raised for discussion and further
      investigation.

PMID- 22879784
TI  - Higher Dietary Protein Intake is Associated with Lower Body Fat in the
      Newfoundland Population.
AB  - BACKGROUND: Increased protein proportions in the diet combined with energy
      restriction has been shown to enhance weight loss during dietary intervention. It
      is not known if the beneficial effect of dietary protein exists in the general
      population under normal living conditions without a negative energy balance.
      METHODS: A total of 1834 participants (n = 443 men, n = 1391 women) were
      recruited from the CODING study. Participants' dietary macronutrient compositions
      were determined through a Willett FFQ. Body composition variables including
      percent body fat (%BF), percent trunk fat (%TF), percent total lean mass (%LM),
      and percent trunk lean mass (%TLM) were determined using DXA. Major confounding
      factors including age, physical activity levels, total caloric intake,
      carbohydrate intake, menopausal status, smoking status and medication use were
      controlled for in all analyses. RESULTS: Significant inverse relationships were
      observed between dietary protein intake (g/kg body weight/day) and weight, waist
      circumference, waist-to-hip ratio, BMI, %BF, and %TF (P < 0.001). Significant
      positive relationships were observed with %LM and %TLM (P < 0.001). Additionally,
      significant differences in weight (12.7 kg in men, 11.4 kg in women), BMI (4.1
      BMI units in men, 4.2 units in women), and %BF (7.6% in men, 6.0% in women) were
      observed between low and high dietary protein consuming groups (P < 0.001).
      Dietary protein explained 11% of the total variation in %BF in the NL population.
      CONCLUSION: This study provides strong evidence that higher protein intake, even
      in the absence of energy restriction, is associated with a more favorable body
      composition in the general population.

PMID- 22879785
TI  - Parathyroid Hormone's Acute Effect on Vasodilatory Function.
AB  - Parathyroid hormone (PTH) seems to affect the risk of cardiovascular disease. The
      aim of the present study was to investigate PTH's acute effect on endothelial
      vasodilatory function in forearm resistance vessels. Ten healthy subjects
      underwent forearm venous occlusion plethysmography. We measured forearm blood
      flow at baseline and at a stable, locally increased PTH level after intra
      arterial infusion of metacholine and nitroprusside. The contralateral arm served
      as a control. Ionized calcium (Ca++) and PTH values were normal in all subjects
      at baseline (1.26 +/- 0.02 mM/L, 3.6 +/- 1.2 pM/L). After 30 minutes of PTH
      infusion, the PTH level increased in the active arm (13.8 +/- 4.0 pM/L P < 0.01),
      while the Ca++ level was unchanged (1.25 +/- 0.04; mM/L). Both the PTH and the
      Ca++ level in the contralateral arm remained unchanged, which indicates no
      systemic influence. The endothelial-dependent vasodilation was inversely
      correlated to the Ca++ level at baseline (r = -0.75, P < 0.05) and after PTH
      infusion (r = -0.68, P < 0.05). The vasodilatory function was not affected during
      PTH-infusion.

PMID- 22879786
TI  - Pioglitazone in the treatment of type 2 diabetes: safety and efficacy review.
AB  - The increase in obesity and the aging of the population has lead to an increase
      in the incidence of type 2 diabetes. This has led to the development of new drugs
      such as thiazolidinediones (TZDs) which are Peroxisome Proliferator-Activated
      Receptor (PPARgamma) agonists, to treat type 2 diabetes. TZDs have recently been
      at the center of a controversy with regards to their cardiovascular safety.
      Pioglitazone is a TZD which has been shown to be effective in glycemic control by
      lowering insulin resistance. Pioglitazone also has beneficial effects on lipid
      metabolism and cardiovascular risk. The safety and efficacy of pioglitazone
      including its pleotropic effects are discussed at length in this article.

PMID- 22879787
TI  - A review of insulin pen devices and use in the elderly diabetic population.
AB  - The prevalence of diabetes mellitus (DM) in the elderly population currently
      represents almost one-half of the overall diabetic population. Treatment of DM
      often requires a multidrug regimen that includes insulin therapy; however, due to
      concomitant comorbidities such as dementia, vision loss, neuropathies, poor
      mobility, and poor manual dexterity, elderly patients may be at increase risk for
      hypoglycemia and other dosing errors that are associated with insulin
      administration. Insulin pen devices have been shown to provide more reliable,
      accurate, and simplified dosing, and therefore may be a safer, easier, and more
      acceptable method of insulin delivery in the elderly population. This review will
      describe the various insulin pen devices available today, as well as discuss the
      potential advantages of these devices in the elderly population.

PMID- 22879788
TI  - Treatment of type 1 and type 2 diabetes mellitus with insulin detemir, a long
      acting insulin analog.
AB  - Insulin detemir is a long-acting basal insulin approved for use in patients with
      type 1 (T1DM) or type 2 diabetes (T2DM). Insulin detemir has demonstrated
      equivalent glycemic control and hypoglycemic risk when compared to insulin
      glargine, and insulin detemir has generally but not consistently demonstrated
      less weight gain than insulin glargine in T2DM. The benefits of basal insulin
      analogs relative to NPH insulin are well recognized, including less FBG
      variability, lower risk of hypoglycemia, and less weight gain specifically with
      insulin detemir. However, NPH insulin continues to be widely prescribed, which
      may be due in part to economic considerations. While NPH insulin generally costs
      less per prescription, insulin detemir has been shown to be cost effective
      compared to NPH insulin as well as insulin glargine. Therefore, insulin detemir
      is an effective option from both clinical and economic perspectives for patients
      with T1DM or T2DM who require basal insulin to achieve glycemic control.

PMID- 22879789
TI  - Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes
      Mellitus.
AB  - The prevalence of type 2 diabetes mellitus is high and growing rapidly.
      Suboptimal glycemic control provides opportunities for new treatment options to
      improve the morbidity and mortality of this progressive disease. Saxagliptin, a
      selective DPP-4 inhibitor, increases endogenous incretin levels and incretin
      acitivty. In controlled clinical trials saxagliptin reduces both fasting and
      postprandial glucose and works in monotherapy and in combination with metformin,
      TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and
      may have other beneficial non-glycemic effects. The authors review the current
      available evidence for the safety, efficacy and saxagliptin's place in therapy
      for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1,
      GIP) expand we may see additional important non-glycemic effects that may affect
      the chronic management of type 2 diabetes mellitus.

PMID- 22879790
TI  - The Clinical Efficacy and Safety of Glucagon-Like Peptide-1 (GLP-1) Agonists in
      Adults with Type 2 Diabetes Mellitus.
AB  - OBJECTIVE: To review the efficacy and safety of glucagon-like peptide-1 (GLP-1)
      agonists to determine their role in type 2 diabetes mellitus (T2DM). DATA
      SOURCES: A Medline search was conducted using the keywords exenatide,
      liraglutide, glucagon-like peptide-1, type 2 diabetes mellitus, hyperglycemia,
      pharmacokinetics, pharmacology and safety. STUDY SELECTION: All identified
      articles written in English were evaluated with priority given to controlled,
      randomized trials including human data. References of identified published trials
      were reviewed for additional trials to be included in the review. DATA SYNTHESIS:
      Exenatide and liraglutide are GLP-1 agonists approved for the treatment of T2DM.
      Several randomized, active and placebo controlled trials examining the efficacy
      and safety of exenatide and liraglutide both as monotherapy and in combination
      therapy have been conducted. Both agents have demonstrated improved glycemic
      control in addition to weight loss and increased beta-cell function. The most
      common adverse effects are gastrointestinal in nature and appear to be transient.
      CONCLUSION: It appears exenatide and liraglutide are safe and effective in the
      treatment of T2DM and may exhibit effects that make them preferred over other
      anti-diabetic medications.

PMID- 22879791
TI  - An unusual case of hypercalcemia associated with graves' disease and vitamin d
      deficiency.
AB  - OBJECTIVE: To present a case of hypercalcemia associated with thyrotoxicosis in a
      patient with vitamin D deficiency and review biochemical changes during the
      course of treatment. METHODS: We report a case, describe the changes in serum
      calcium, phosphorus, parathyroid hormone in Graves' disease and concomitant
      Vitamin D deficiency. We compare our findings to those reported in literature.
      RESULTS: Our patient had hypercalcemia secondary to thyrotoxicosis alone, which
      was confirmed by low parathyroid hormone level and resolution of hypercalcemia
      with treatment of thyrotoxicosis. The case was complicated by a concomitant
      vitamin D deficiency. Serum calcium elevation in patients with thyrotoxicosis
      occurs secondary to hyperthyroidism alone or due to concurrent
      hyperparathyroidism. Hypercalcemia from thyrotoxicosis is usually asymptomatic
      and is related to bone resorption. Vitamin D deficiency can be seen in patients
      with thyrotoxicosis because of accelerated metabolism, poor intestinal absorption
      and increased demand during bone restoration phase. Coexistence of hypercalcemia
      and Vitamin D deficiency in patients with thyrotoxicosis is rare, but possible,
      and 25-hydroxyvitamin D levels should be checked. The definite treatment for
      hypercalcemia in thyrotoxicosis is correction of thyroid function. CONCLUSION:
      Hypercalcemia in thyrotoxicosis should be distinguished from concomitant
      hyperparathyroidism and confirmed by resolution of hypercalcemia with control of
      thyrotoxicosis. Patients with hypercalcemia and thyrotoxicosis may also have
      vitamin D deficiency and 25-OH Vitamin D levels should be checked.

PMID- 22879792
TI  - Updated review: improved glycemic control with repaglinide-metformin in fixed
      combination for patients with type 2 diabetes.
AB  - As the prevalence of type 2 diabetes continues to rise, new drug therapies will
      need to be explored to prevent morbidity and mortality associated with diabetes
      as well as growing health care costs. Type 2 diabetes is characterized by
      decreased insulin secretion and sensitivity. Numerous oral medications are
      currently approved for the treatment of type 2 diabetes. A treat-to-failure
      approach has traditionally been adopted with step-wise additions of oral
      medications; however, a growing frequency of treatment failures with monotherapy
      has led to the use of combination therapies earlier in the treatment of type 2
      diabetes. One such combination regimen is repaglinide (a prandial glucose
      optimizer that increases insulin release) plus metformin (an insulin sensitizer
      that inhibits hepatic glucose output and increases peripheral glucose uptake
      while minimizing weight gain). Findings from several clinical trials have shown
      repaglinide plus metformin combination therapy to be superior to either
      monotherapy with significant reductions in hemoglobin A1C and fasting glucose
      values. Repaglinide used in combination also has shown less incidence of
      hypoglycemia compared with other combination therapies such as sulphonylureas
      plus metformin. Repaglinide plus metformin combination therapy appears to be a
      valuable therapeutic option for type 2 diabetic patients seeking a less complex
      drug regimen while potentially achieving better glucose control if currently
      inadequately controlled on monotherapy.

PMID- 22879793
TI  - Type 1 Diabetes Mellitus Associated with Pegylated Interferon-alpha Plus
      Ribavirin Treatment for Chronic Hepatitis C: Case Report and Literature Review.
AB  - Combined pegylated interferon (PEG-IFN)+ribavirin (RBV) therapy has been used as
      a primary treatment for chronic hepatitis C. However, IFN-induced autoimmune
      disease, including type 1 diabetes mellitus, has been highlighted as one of the
      problems with this therapy. Here we report the case of a patient who developed
      type 1 diabetes mellitus during combined PEG-IFN+RBV therapy for hepatitis C but
      who showed no exacerbation of diabetes despite continued use of IFN. A 63-year
      old man with chronic hepatitis C and a nonresponder to previous IFNalpha
      treatments, was admitted to our hospital because of excessive thirst, polydipsia,
      and polyuria 24 weeks after the start of PEG-IFNalpha+RBV therapy. High levels of
      blood glucose and glycosylated hemoglobin and low levels of C-peptide and
      immunoreactive insulin were observed. The serum antiglutamic acid decarboxylase
      antibody titer was 27,700 U/mL. We diagnosed IFN-induced type 1 diabetes
      mellitus; however PEG-IFNalpha+RBV therapy was continued for 48 weeks. Serum HCV
      remains negative five years after this treatment. Intensive insulin therapy was
      started immediately after the diagnosis of type 1 diabetes. Although the patient
      initially required 22 U/day of insulin, the dosage could be gradually reduced
      after completion of PEG-IFNalpha+RBV therapy and blood glucose remained well
      controlled. Prediction of onset of type 1 diabetes mellitus on the basis of
      baseline measurement of pancreas-associated autoantibodies is difficult.
      Therefore, it would be advisable to consider the possibility of onset of type 1
      diabetes mellitus in all patients receiving IFN+RBV therapy.

PMID- 22879794
TI  - Liraglutide in adults with type 2 diabetes: global perspective on safety,
      efficacy and patient preference.
AB  - Incretin-based therapies have been gaining much attention recently as a new class
      of therapeutics for type 2 diabetes worldwide. Among them, glucagon-like peptide
      1 receptor agonist liraglutide has been rapidly increasing its global usage. Once
      daily injection of liraglutide significantly ameliorates glycemic control in
      patients with type 2 diabetes by enhancing insulin secretion and suppressing
      glucagon secretion glucose-dependently. Liraglutide delays gastric emptying and
      suppresses food intakes, both of which contribute to glucose lowering and weight
      reduction. Efficacy and safety of liraglutide in management of type 2 diabetes
      have been well documented in several key clinical trials such as series of phase
      3 Liraglutide Effect and Action in Diabetes (LEAD) trials, and the liraglutide
      versus-sitagliptin trial. Recent two trials dealing with monotherapy and
      sulfonylurea combination therapy on Japanese patients with type 2 diabetes
      furthermore indicate liraglutide's effectiveness in non-obese diabetes. In this
      review, we summarize results from such clinical trials, and discuss efficacy and
      safety of liraglutide in management of type 2 diabetes in various countries,
      along with a pitfall of liraglutide usage in real clinical setting.

PMID- 22879795
TI  - Linagliptin-a novel dipeptidyl peptidase inhibitor for type 2 diabetes therapy.
AB  - Incretin based therapies have been introduced into the treatment options of type
      2 diabetes a few years ago. Among them, the orally active DPP-4 inhibitors have
      established themselves as insulinotropic agents. Their advantage is the glucose
      dependent insulinotropic action without an intrinsic risk for causing
      hypoglycemia. Additionally DPP-4 inhibitors have a glucose dependent
      glucagonostatic action contributing to improved glucose control. They are weight
      neutral and show a good safety and tolerability profile with comparable efficacy
      to sulfonylureas. Linagliptin is a novel DPP-4 inhibitor with a distinct
      pharmacological profile. In contrast to the other approved DPP-4 inhibitors it is
      eliminated by a hepatic/biliary route rather than a renal route. Therefore no
      dose adjustment is recommended in patients with type 2 diabetes and renal
      impairment. In clinical studies, it has been shown to be non-inferior to
      sulfonylurea treatment regarding glycemic parameters, but to possess favourable
      safety advantages regarding hypoglycemia frequency, body weight development and
      effects on cardioavascular parameters. This article gives an overview on the
      pharmacology of linagliptin as well as on the clinical data available.

PMID- 22879797
TI  - Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?
AB  - The advances in recombinant DNA technology have led to an improvement in the
      properties of currently available long-acting insulin analogs. Insulin degludec,
      a new generation ultra-long-acting basal insulin, currently in phase 3 clinical
      trials, has a promising future in clinical use. When compared to its rival basal
      insulin analogs, a longer duration of action and lower incidence of hypoglycemic
      events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its
      unique mechanism of action is based on multihexamer formation after subcutaneous
      injection. This reportedly allows for less pharmacodynamic variability and within
      subject variability than currently available insulin analogs, and a duration of
      action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin
      degludec is yet another factor that would be taken into consideration when
      choosing the optimal basal insulin for a diabetic individual.4 A formulation of
      insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit
      improved flexibly of dosing without compromising glycemic control or safety.5.

PMID- 22879796
TI  - Rosuvastatin and atorvastatin: comparative effects on glucose metabolism in non
      diabetic patients with dyslipidaemia.
AB  - The ever increasing interventional CVD outcome studies have resulted in statins
      being an essential factor of cardiovascular prevention strategies. The JUPITER
      study in 2008, despite reducing CVD and overall mortality, highlighted an
      increase in new onset diabetes in the rosuvastatin treated arm. Since then there
      have been many meta-analyses of the RCTs and the largest carried out by Sattar et
      al showed a significant increase in the incidence of diabetes during the trials.
      The findings from the individual studies when comparing the different statins
      were less clear. A higher statin dosage and risk factors associated with diabetes
      appeared to predict this phenomenon. There have been many studies investigating
      the effects of statins on glycaemic control, but again no clear conclusion is
      apparent. Despite the increase in new onset diabetes observed, the risk is
      clearly out-weighed by the CVD benefits observed in nearly all the statin trials.
      Thus, no change is required to any of the prevention guidelines regarding
      statins. However, it may be prudent to monitor glycaemic control after commencing
      statin therapy. This review will focus on atorvastatin which is the most widely
      used statin worldwide and rosuvastatin which is the most efficacious. This will
      be against a background of the effects of other statins on glucose metabolism in
      non-diabetic patients.

PMID- 22879798
TI  - Role of teriparatide in accelerating metatarsal stress fracture healing: a case
      series and review of literature.
AB  - Bone fractures are one of the leading causes of emergency room visits worldwide,
      with approximately 8 million bony fractures occurring annually in the US alone.
      Although the majority of fractures do not cause significant long-term morbidity
      and mortality, approximately 10% of these fractures result in impaired fracture
      healing, drastically affecting quality of life in affected patients. By
      increasing bone formation, teriparatide, an anabolic agent used in the treatment
      of postmenopausal osteoporosis, has shown promise in accelerating the rate of
      fracture healing. We present two patients with impaired healing of metatarsal
      fractures who were subsequently treated with teriparatide. Both patients
      experienced successful bony union of the fracture after the use of teriparatide.
      These findings suggest that teriparatide may be useful in the clinical setting
      for the acceleration of fracture healing, especially in patients who are at risk
      for impaired fracture healing.

PMID- 22879799
TI  - Using AIC in Multiple Linear Regression framework with Multiply Imputed Data.
AB  - Many model selection criteria proposed over the years have become common
      procedures in applied research. However, these procedures were designed for
      complete data. Complete data is rare in applied statistics, in particular in
      medical, public health and health policy settings. Incomplete data, another
      common problem in applied statistics, introduces its own set of complications in
      light of which the task of model selection can get quite complicated. Recently,
      few have suggested model selection procedures for incomplete data with varying
      degrees of success. In this paper we explore model selection by the Akaike
      Information Criterion (AIC) in the multivariate regression setting with ignorable
      missing data accounted for via multiple imputation.

PMID- 22879800
TI  - Family Functioning and Externalizing Behaviour among Low-income Children: Self
      regulation as a Mediator.
AB  - The purpose of this study was to examine self-regulation as a mediator of the
      relation between family functioning and externalizing behaviour in 731 low-income
      children (M age = 41 months) across three time points. Specifically, this study
      focused on whether chaos in the home and positive behaviour support were
      indirectly related to externalizing problems through their influence on
      inhibitory control. The primary findings were as follows: (a) chaos in the home
      at age 3 years was indirectly related to externalizing behaviour at age 5.5 years
      through children's inhibitory control at age 4 years, and (b) positive behaviour
      support at age 3 years was indirectly related to externalizing behaviour at age
      5.5 years through inhibitory control at age 4 years. Implications of these
      findings and directions for future research are discussed.

PMID- 22879801
TI  - A call for increased librarian support for the medical humanities.

PMID- 22879802
TI  - Response to "Evolution, revolution, or obsolescence: an examination of writings
      on the future of health sciences libraries".

PMID- 22879803
TI  - Jane Blumenthal, AHIP Medical Library Association President, 2012-2013.

PMID- 22879804
TI  - Building projects: redefining hospital libraries.

PMID- 22879805
TI  - A case study: the evolution of a "facilitator model" liaison program in an
      academic medical library.
AB  - QUESTION: What type of liaison program would best utilize both librarians and
      other library staff to effectively promote library services and resources to
      campus departments? SETTING: The case is an academic medical center library
      serving a large, diverse campus. METHODS: The library implemented a "facilitator
      model" program to provide personalized service to targeted clients that allowed
      for maximum staff participation with limited subject familiarity. To determine
      success, details of liaison-contact interactions and results of liaison and
      department surveys were reviewed. RESULTS: Liaisons successfully recorded 595
      interactions during the program's first 10 months of existence. A significant
      majority of departmental contact persons (82.5%) indicated they were aware of the
      liaison program, and 75% indicated they preferred email communication.
      CONCLUSION: The "facilitator model" provides a well-defined structure for
      assigning liaisons to departments or groups; however, training is essential to
      ensure that liaisons are able to communicate effectively with their clients.

PMID- 22879806
TI  - Improving information retrieval using Medical Subject Headings Concepts: a test
      case on rare and chronic diseases.
AB  - BACKGROUND: As more scientific work is published, it is important to improve
      access to the biomedical literature. Since 2000, when Medical Subject Headings
      (MeSH) Concepts were introduced, the MeSH Thesaurus has been concept based.
      Nevertheless, information retrieval is still performed at the MeSH Descriptor or
      Supplementary Concept level. OBJECTIVE: The study assesses the benefit of using
      MeSH Concepts for indexing and information retrieval. METHODS: Three sets of
      queries were built for thirty-two rare diseases and twenty-two chronic diseases:
      (1) using PubMed Automatic Term Mapping (ATM), (2) using Catalog and Index of
      French-language Health Internet (CISMeF) ATM, and (3) extrapolating the MEDLINE
      citations that should be indexed with a MeSH Concept. RESULTS: Type 3 queries
      retrieve significantly fewer results than type 1 or type 2 queries (about 18,000
      citations versus 200,000 for rare diseases; about 300,000 citations versus
      2,000,000 for chronic diseases). CISMeF ATM also provides better precision than
      PubMed ATM for both disease categories. DISCUSSION: Using MeSH Concept indexing
      instead of ATM is theoretically possible to improve retrieval performance with
      the current indexing policy. However, using MeSH Concept information retrieval
      and indexing rules would be a fundamentally better approach. These modifications
      have already been implemented in the CISMeF search engine.

PMID- 22879807
TI  - The persistence of error: a study of retracted articles on the Internet and in
      personal libraries.
AB  - OBJECTIVE: To determine the accessibility of retracted articles residing on non
      publisher websites and in personal libraries. METHODS: Searches were performed to
      locate Internet copies of 1,779 retracted articles identified in MEDLINE,
      published between 1973 and 2010, excluding the publishers' website. Found copies
      were classified by article version and location. Mendeley (a bibliographic
      software) was searched for copies residing in personal libraries. RESULTS: Non
      publisher websites provided 321 publicly accessible copies for 289 retracted
      articles: 304 (95%) copies were the publisher' versions, and 13 (4%) were final
      manuscripts. PubMed Central had 138 (43%) copies; educational websites 94 (29%);
      commercial websites 24 (7%); advocacy websites 16 (5%); and institutional
      repositories 10 (3%). Just 16 [corrected] (5%) full-article views included a
      retraction statement. Personal Mendeley libraries contained records for 1,340
      (75%) retracted articles, shared by 3.4 users, on average. CONCLUSIONS: The
      benefits of decentralized access to scientific articles may come with the cost of
      promoting incorrect, invalid, or untrustworthy science. Automated methods to
      deliver status updates to readers may reduce the persistence of error in the
      scientific literature.

PMID- 22879808
TI  - Teaching evidence-based medicine literature searching skills to medical students
      during the clinical years: a randomized controlled trial.
AB  - OBJECTIVES: Constructing an answerable question and effectively searching the
      medical literature are key steps in practicing evidence-based medicine (EBM).
      This study aimed to identify the effectiveness of delivering a single workshop in
      EBM literature searching skills to medical students entering their first clinical
      years of study. METHODS: A randomized controlled trial was conducted with third
      year undergraduate medical students. Participants were randomized to participate
      in a formal workshop in EBM literature searching skills, with EBM literature
      searching skills and perceived competency in EBM measured at one-week post
      intervention via the Fresno tool and Clinical Effectiveness and Evidence-Based
      Practice Questionnaire. RESULTS: A total of 121 participants were enrolled in the
      study, with 97 followed-up post-intervention. There was no statistical mean
      difference in EBM literature searching skills between the 2 groups (mean
      difference = 0.007 (P = 0.99)). Students attending the EBM workshop were
      significantly more confident in their ability to construct clinical questions and
      had greater perceived awareness of information resources. CONCLUSIONS: A single
      EBM workshop did not result in statistically significant changes in literature
      searching skills. Teaching and reinforcing EBM literature searching skills during
      both preclinical and clinical years may result in increased student confidence,
      which may facilitate student use of EBM skills as future clinicians.

PMID- 22879809
TI  - The Internet and health information: differences in pet owners based on age,
      gender, and education.
AB  - OBJECTIVE: The research assessed the attitudes and behaviors of pet owners
      pertaining to online search behavior for pet health information. METHODS: A
      survey was conducted with a random sample of pet owners drawn from two US
      metropolitan areas and surrounding cities. Participating clinics were chosen
      randomly, and each participating clinic was asked to distribute 100 surveys to
      their clients until all surveys were disbursed. RESULTS: Although some
      perceptions and behaviors surrounding the use of the Internet for pet health
      information differ based on gender, age, or education level of pet owners, there
      are many aspects in which there are no differences based on these demographics.
      CONCLUSIONS: Results of the study suggest that closer examination of the common
      perception that gender, age, or education level has an effect on Internet
      behavior as it relates to veterinary medicine is required. Recommendations are
      made pertaining to the growing presence of the Internet and its impact on
      veterinary medicine.

PMID- 22879810
TI  - Health information seekers in Japan: a snapshot of needs, behavior, and
      recognition in 2008.
AB  - OBJECTIVES: The purpose of this study was to explore the latest information
      seeking behavior among health care consumers in Japan and to compare these
      behaviors with those recorded in similar surveys administered in Japan and the
      United States after 2000. METHOD: The authors conducted a randomized, population
      based, door-to-door survey in 2008. A total of 1,200 Japanese adults over 15
      years of age completed the questionnaire. MAIN RESULTS: The results from 1,189
      valid responses indicated that slightly more than half the number of participants
      had actively sought health information during the previous 2 years. Most seekers
      looked for information on a specific disease. "Physicians" remained the
      respondents' first choice as an information source, while "Internet" has gained
      greater popularity as a resource since the previous survey in 2000. Half the
      number of participants stated that they were willing to read academic or
      professional medical journal articles if written in Japanese and provided free of
      charge. CONCLUSION: The evidence indicates that Japanese health care consumers
      are now proactively seeking health information. These consumers feel reassured by
      the information they can access and would like to read clinical research in their
      native language.

PMID- 22879811
TI  - The new Medical Library Association research agenda: final results from a three
      phase Delphi study.

PMID- 22879812
TI  - Applications of information and communication technologies in libraries in
      Pakistan.

PMID- 22879813
TI  - Improving an outreach service by analyzing the relationship of health information
      disparities to socioeconomic indicators using geographic information systems.

PMID- 22879815
TI  - Cancer patients' use of pharmaceutical patient assistance programs in the
      outpatient pharmacy at a large tertiary cancer center.
AB  - PURPOSE: To report on the use of pharmaceutical patient assistance programs
      (PAPs) in the outpatient pharmacy at the largest tertiary cancer center in the
      United States.  METHODS: We conducted a retrospective (July 1, 2006-Dec 31,2007)
      cross-sectional analysis of outpatient pharmacy, medical, and cancer registry
      records at the cancer center. The cancer center identified 104 medications
      available through PAPs. Study-eligible patients received at least one of these
      medications, either as a PAP case patient or as a PAP control non-user. Binary
      logit regression models predicted PAP use, and descriptive statistics compared
      PAP user and non-user medication fills.  RESULTS: Of 25,552 cancer patients at
      who received an outpatient medication during the study period, 1,929 met study
      criteria (n=950 PAP users, 979 PAP non-users). In comparison to controls, PAP
      users were more likely to be uninsured (odds ratio (OR)=4.60, 95% confidence
      interval (CI): 2.118, 9.970), indigent (OR=16.95, 95% CI: 6.845, 41.960), and <
      65 years old (OR=2.31, 95% CI: 1.517, 3.509). Of the most frequently dispensed
      medications to PAP users from PAPs (n=5,271), 88% (n=4,936) were for supportive
      care (e.g., nausea/vomiting). PAPs provided 35% (n=842) of the most common
      anticancer agents administered to PAP users (n=1,296), accounting for a monthly
      mean of $55,000 in pharmaceutical expenditures.  CONCLUSIONS: In the cancer
      center's outpatient pharmacy, PAPs provided financial support for about a third
      of the most commonly used therapies, primarily for supportive care indications,
      for a small percentage of eligible cancer patients.

PMID- 22879814
TI  - CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock.
AB  - Eukaryotic circadian clocks rely on transcriptional feedback loops. In
      Drosophila, the PERIOD (PER) and TIMELESS (TIM) proteins accumulate during the
      night, inhibit the activity of the CLOCK (CLK)/CYCLE (CYC) transcriptional
      complex, and are degraded in the early morning. The control of PER and TIM
      oscillations largely depends on post-translational mechanisms. They involve both
      light-dependent and light-independent pathways that rely on the phosphorylation,
      ubiquitination, and proteasomal degradation of the clock proteins. SLMB, which is
      part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the
      circadian degradation of phosphorylated PER. We show here that CULLIN-3 (CUL-3)
      is required for the circadian control of PER and TIM oscillations. Expression of
      either Cul-3 RNAi or dominant negative forms of CUL-3 in the clock neurons alters
      locomotor behavior and dampens PER and TIM oscillations in light-dark cycles. In
      constant conditions, CUL-3 deregulation induces behavioral arrhythmicity and
      rapidly abolishes TIM cycling, with slower effects on PER. CUL-3 affects TIM
      accumulation more strongly in the absence of PER and forms protein complexes with
      hypo-phosphorylated TIM. In contrast, SLMB affects TIM more strongly in the
      presence of PER and preferentially associates with phosphorylated TIM. CUL-3 and
      SLMB show additive effects on TIM and PER, suggesting different roles for the two
      ubiquitination complexes on PER and TIM cycling. This work thus shows that CUL-3
      is a new component of the Drosophila clock, which plays an important role in the
      control of TIM oscillations.

PMID- 22879817
TI  - Developing and costing local strategies to improve maternal and child health: the
      investment case framework.

PMID- 22879816
TI  - Feasibility, yield, and cost of active tuberculosis case finding linked to a
      mobile HIV service in Cape Town, South Africa: a cross-sectional study.
AB  - BACKGROUND: The World Health Organization is currently developing guidelines on
      screening for tuberculosis disease to inform national screening strategies. This
      process is complicated by significant gaps in knowledge regarding mass screening.
      This study aimed to assess feasibility, uptake, yield, treatment outcomes, and
      costs of adding an active tuberculosis case-finding program to an existing mobile
      HIV testing service. METHODS AND FINDINGS: The study was conducted at a mobile
      HIV testing service operating in deprived communities in Cape Town, South Africa.
      All HIV-negative individuals with symptoms suggestive of tuberculosis, and all
      HIV-positive individuals regardless of symptoms were eligible for participation
      and referred for sputum induction. Samples were examined by microscopy and
      culture. Active tuberculosis case finding was conducted on 181 days at 58
      different sites. Of the 6,309 adults who accessed the mobile clinic, 1,385 were
      eligible and 1,130 (81.6%) were enrolled. The prevalence of smear-positive
      tuberculosis was 2.2% (95% CI 1.1-4.0), 3.3% (95% CI 1.4-6.4), and 0.4% (95% CI
      1.4 015-6.4) in HIV-negative individuals, individuals newly diagnosed with HIV,
      and known HIV, respectively. The corresponding prevalence of culture-positive
      tuberculosis was 5.3% (95% CI 3.5-7.7), 7.4% (95% CI 4.5-11.5), 4.3% (95% CI 2.3
      7.4), respectively. Of the 56 new tuberculosis cases detected, 42 started
      tuberculosis treatment and 34 (81.0%) completed treatment. The cost of the
      intervention was US$1,117 per tuberculosis case detected and US$2,458 per
      tuberculosis case cured. The generalisability of the study is limited to similar
      settings with comparable levels of deprivation and TB and HIV prevalence.
      CONCLUSIONS: Mobile active tuberculosis case finding in deprived populations with
      a high burden of HIV and tuberculosis is feasible, has a high uptake, yield, and
      treatment success. Further work is now required to examine cost-effectiveness and
      affordability and whether and how the same results may be achieved at scale.

PMID- 22879818
TI  - Legal disputes over duties to disclose treatment risks to patients: a review of
      negligence claims and complaints in Australia.

PMID- 22879819
TI  - Retraction: Multi-scale inference of interaction rules in animal groups using
      Bayesian model selection.

PMID- 22879820
TI  - Cedar virus: a novel Henipavirus isolated from Australian bats.
AB  - The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra
      virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural
      reservoir. Each virus also causes serious and commonly lethal infection of people
      as well as various species of domestic animals, however little is known about the
      associated mechanisms of pathogenesis. Here, we report the isolation and
      characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV),
      which shares significant features with the known henipaviruses. The genome size
      (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its
      nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and
      it uses the same receptor molecule (ephrin-B2) for entry during infection.
      Preliminary challenge studies with CedPV in ferrets and guinea pigs, both
      susceptible to infection and disease with known henipaviruses, confirmed virus
      replication and production of neutralizing antibodies although clinical disease
      was not observed. In this context, it is interesting to note that the major
      genetic difference between CedPV and HeV or NiV lies within the coding strategy
      of the P gene, which is known to play an important role in evading the host
      innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the
      CedPV P gene lacks both RNA editing and also the coding capacity for the highly
      conserved V protein. Preliminary study indicated that CedPV infection of human
      cells induces a more robust IFN-beta response than HeV.

PMID- 22879822
TI  - Parental Methamphetamine Use and Manufacture: Child and Familial Outcomes.
AB  - The children of methamphetamine (MA) users and manufacturers are at high risk of
      neglect and abuse and physical harm from exposure to the drug and the chemicals
      used to produce it. This study is the first to document the epidemiology of
      children removed from home-based MA labs and their familial outcomes. Analyses
      are predominantly descriptive for 99 cases of drug-endangered children recorded
      from 2001-2003 in Los Angeles County. Neglect was substantiated in 93% of the
      cases; 97% of the cases resulted in child protective services detainment. Eighty
      percent had a documented medical diagnosis, most often related to exposure to MA
      manufacture.

PMID- 22879821
TI  - A general G1/S-phase cell-cycle control module in the flowering plant Arabidopsis
      thaliana.
AB  - The decision to replicate its DNA is of crucial importance for every cell and, in
      many organisms, is decisive for the progression through the entire cell cycle. A
      comparison of animals versus yeast has shown that, although most of the involved
      cell-cycle regulators are divergent in both clades, they fulfill a similar role
      and the overall network topology of G1/S regulation is highly conserved. Using
      germline development as a model system, we identified a regulatory cascade
      controlling entry into S phase in the flowering plant Arabidopsis thaliana,
      which, as a member of the Plantae supergroup, is phylogenetically only distantly
      related to Opisthokonts such as yeast and animals. This module comprises the
      Arabidopsis homologs of the animal transcription factor E2F, the plant homolog of
      the animal transcriptional repressor Retinoblastoma (Rb)-related 1 (RBR1), the
      plant-specific F-box protein F-BOX-LIKE 17 (FBL17), the plant specific cyclin
      dependent kinase (CDK) inhibitors KRPs, as well as CDKA;1, the plant homolog of
      the yeast and animal Cdc2+/Cdk1 kinases. Our data show that the principle of a
      double negative wiring of Rb proteins is highly conserved, likely representing a
      universal mechanism in eukaryotic cell-cycle control. However, this negative
      feedback of Rb proteins is differently implemented in plants as it is brought
      about through a quadruple negative regulation centered around the F-box protein
      FBL17 that mediates the degradation of CDK inhibitors but is itself directly
      repressed by Rb. Biomathematical simulations and subsequent experimental
      confirmation of computational predictions revealed that this regulatory circuit
      can give rise to hysteresis highlighting the here identified dosage sensitivity
      of CDK inhibitors in this network.

PMID- 22879823
TI  - Impact of Drug-Resistance Polymerase Mutations on the Replication of HBeAg
      Positive and HBeAg-Negative Hepatitis B Virus Strains in Vitro.

PMID- 22879824
TI  - Treatment of patients with HCV related cirrhosis: many rewards with very few
      risks.
AB  - Antiviral treatment of chronic hepatitis C virus (HCV) is aimed at the persistent
      eradication of the virus, the so-called sustained virological response (SVR),
      with the aim ultimately being to prevent the development of liver-related
      complications and improve patients' survival. Patients with HCV-related
      compensated cirrhosis are the group most likely to benefit from viral clearance,
      as several retrospective studies have shown liver complications rates to be
      positively modified by the achievement of a SVR. Whether these benefits rely on
      viral clearance or on the histological improvements seen following successful
      interferon (IFn)-based therapies has recently been a matter for debate, as
      studies have shown cirrhosis to regress in some patients with a SVR. Whatever the
      mechanisms, cirrhosis has the uncanny ability to be both a dominant indication
      for therapy, as well as one of the strongest baseline factors associated with
      reduced efficacy of any IFn-based regimen. This has led to the development of
      alternative treatment strategies, such as low dose pegylated IFn (PegIFn)
      monotherapy, that unfortunately has proven to be of limited efficacy. For this
      reason regimens able to clear the virus without relying on the broad antiviral
      effect of IFN are eagerly awaited.

PMID- 22879825
TI  - Statins in the treatment of hepatitis C.

PMID- 22879826
TI  - Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major
      patients; new indications for combination therapy.
AB  - BACKGROUND: Treatment guidelines contraindicate ribavirin for treatment of
      hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless,
      the current evidence suggests that ribavirin might be tolerated by these
      patients. OBJECTIVES: Despite this evidence, low dose ribavirin combination
      therapy has not been compared with peginterferon monotherapy in these patients so
      far. PATIENTS AND METHODS: Two hundred eighty thalassemia patients with
      detectable HCV-RNA PCR (>= 50 IU/mL) and liver histology consistent with chronic
      HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81)
      monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according
      to hemoglobin levels (n = 199). Treatment experienced patients were eligible for
      this study. RESULTS: Sustained virological response (SVR) was significantly
      higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In
      multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI
      1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups
      of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL,
      previous treatment failure, genotype 1, positive history of splenectomy, fibrosis
      score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due
      to the safety concerns were comparable between the treatment groups (6.5 and 8
      %). Furthermore, transfusion intervals were almost halved in patients who
      received low dose ribavirin. CONCLUSIONS: According to the present study, adult
      thalassemia patients with HCV infection can be treated successfully with low dose
      ribavirin. Hence, we strongly advise combination therapy in thalassemia patients
      with aforementioned clinical characteristics. Moreover, ribavirin does not seem
      to be beneficial in thalassemia patients below 18 years of age.

PMID- 22879827
TI  - Changing pattern of hepatitis a virus epidemiology in an area of high endemicity.
AB  - BACKGROUND: Continuous assessment of hepatitis A virus (HAV) seroepidemiology is
      a useful tool to control the risk of infection. OBJECTIVES: This study aimed to
      evaluate the changing patterns of anti-HAV seroprevalence in a population,which
      isgenerally considered to be anarea ofhigh endemicity. PATIENTS AND METHODS:
      Overall, the results of 3349 sera collected during the period 2005-2008 from
      patients attending the University Hospital of Cagliari, Italy were studied; their
      mean age was 52.7 years, (s + 16.22). Patients with liver disease were excluded
      from the study. Age specific seroprevalence results were compared with those
      observed in similar previous studies carried out in the same area. RESULTS: The
      overall prevalence of anti-HAV was 74.6% with consistently lower values in
      subjects younger than 40 years (17.5%; P < 0.0001) particularly in those under 30
      years of age (8.9%, CI 5.8-11.9). A significant declining trend in age specific
      seroprevalence has been foundin people under 30 years;61% in 1988, 33% in 1995
      and 8.9% in 2005-2008. CONCLUSIONS: Our findings show that a significant decline
      inherd immunity has occurred in the last 20 years as a consequence of lower HAV
      circulation due to improvementsin socio-economical and hygienic conditions.
      Adolescents and young adults are becoming increasingly susceptible to HAV
      infections, as recent outbreaks of acute HAV hepatitis have occurred. Persistent
      environmental monitoring and the implementation of prevention measures must be
      considered in order to contain the risk related to this epidemiological shift.

PMID- 22879828
TI  - Seroprevalence of hepatitis e virus varies considerably among chinese provinces.
AB  - BACKGROUND: Hepatitis E is a common infection in China, but few studies have been
      carried out to compare regional and ethnic factors in its prevalence. OBJECTIVES:
      To characterize the seroprevalence of anti-HEV IgM and IgG in the general
      population of 11 Chinese provinces and in the people from different ethnic
      minorities. MATERIALS AND METHODS: Sera from 14208 people including 723 people
      from four ethnic minorities were screened for anti-HEV IgM and IgG by enzyme
      linked immunosorbent assay (ELISA). For the anti-HEV IgM positive samples,
      reverse transcription-polymerase chain reaction (RT-PCR) was carried out for the
      detection of HEV RNA. RESULTS: The overall prevalence of anti-HEV IgG was 19.7%.
      The highest rate was 35.7% in Guizhou, while the lowest rate was 5.5% in Shanxi.
      Significantly higher rates were found among males compared to females in Hebei
      and Hunan province, and among females compared to males in Chongqing and Shannxi.
      In Guizhou, the prevalence rates among the Buyi, Miao, Shui and Han ethnic groups
      were 41.8%, 32.0%, 37.5% and 34.7%, respectively, which were not significantly
      different. The results also showed that the anti-HEV IgG detection rates
      increased with age for each ethnic group. Additionally, four samples were tested
      positive for anti-HEV IgM but HEV RNA was not detectable. CONCLUSIONS: HEV
      prevalence varies considerably among Chinese provinces. Thus, prevention and
      control programs including vaccination could be specifically targeted to people
      living in regions with relatively higher prevalences.

PMID- 22879829
TI  - The evaluation of hepatitis C virus core antigen in immunized BALB/c mice.
AB  - BACKGROUND: Hepatitis infection represents one of the important causes of
      morbidity and mortality in developing countries, however there is not any
      effective vaccine against hepatitis C which is one of the significant problems in
      vaccine project. OBJECTIVES: The aim of the present study is to evaluate the role
      of HCV core protein in inducing IFN-Gamma secretion and TCL activities as a
      vaccine in Balb/C mice. MATERIAL AND METHODS: Our previous cloned plasmid (HCV
      Core gene into pETDuet-1) applied for protein expression in bacteria. The
      expressed and purified recombinant protein together with Freund's adjuvant was
      injected to 15 Balb/c mice. The total IgG and IgG2a of immunized mice sera were
      evaluated after a week. Two weeks after booster injection, we studied the
      proliferation and IFNgamma secretion of spleens, inguinal and popliteal lymph
      nodes lymphocytes by ELISA and ELISPOT. RESULTS: The FSFC (Frequency of spot
      forming cells) of secreting cells of immunized mice with HCV/Core protein and
      sera IgG2a were considerably higher than the control groups. CONCLUSIONS: The
      core protein together with proper adjuvant can be a candidate vaccine against of
      HCV infection.

PMID- 22879830
TI  - Hepatitis C viral heterogeneity based on core gene and an attempt to design small
      interfering RNA against strains resistant to interferon in rawalpindi, pakistan.
AB  - BACKGROUND: Global prevalence of Hepatitis C Virus (HCV) infection corresponds to
      about 130 million HCV positive patients worldwide. The only drug that effectively
      reduces viral load is interferon-alpha (IFN-alpha) and currently combination of
      IFN and ribavirin is the choice for treatment. OBJECTIVES: The present study is
      aimed to resolve the genotypes based on core gene that might affect the response
      to interferon therapy. Furthermore an attempt was made to propose a powerful
      therapeutic approach by designing the siRNA from sequences of the same patients
      who remain resistant to IFN in this study. PATIENTS AND METHODS: To achieve the
      objectives, a sequence analysis was performed in five HCV ELISA positive subjects
      who have completed IFN treatment. Neighbor Joining (NJ) method was used to study
      the evolutionary relationship. Atomic models were predicted using online software
      PROCHECK and i- TASSER. RESULTS: Two new genotypes were reported for the first
      time namely 4a from suburban region of Rawalpindi and 6e from all over the
      Pakistan. According to Ramachandran plot, satisfactory atomic model was
      considered useful for further studies, i.e. to calculate HCV genotypes
      conservation at structural level, to find out critical binding sites for drug
      designing, or to silence those binding sites by using appropriate siRNA. Single
      siRNA can be used to inhibit HCV RNA synthesis against genotype 3 and 4, as the
      predicted siRNA were originated from the same domain in studied HCV core region
      in both genotypes. CONCLUSIONS: We can conclude that any change or mutation in
      core region might be the cause of HCV strains to resist against IFN therapy.
      Therefore, further understanding of the complex mechanism involved in disrupting
      viral response to therapy would facilitate the development of more effective
      therapeutic regimens. Additionally, a single designed siRNA can be used as an
      alternative for current therapy against more than one resistant HCV genotypes.

PMID- 22879831
TI  - Liver Hemangioma Might Lead to overestimation of Liver Fibrosis by Fibroscan; A
      Missed Issue in Two Cases.
AB  - BACKGROUND: The assessment of liver fibrosis is an important way for prediction
      of liver disease progression and patient's prognosis. Liver stiffness measurement
      (LSM) is strongly associated with stage of liver diseases. overestimation of
      liver fibrosis in heart failure has been reported. We would like to introduce a
      new leading cause of liver fibrosis overestimation by presentation of two cases.
      CASE PRESENTATION: one case with right lobe hemangioma has an overestimation of
      liver fibrosis. The result completely changed when Fibroscan was performed in
      patient's left lobe. Interestingly, another case with left lobe hemangioma had
      overestimation of fibrosis in her left lobe but, right lob Fibroscan was normal.
      CONCLUSION: We found that liver hemangioma may leads to overestimation of liver
      stiffness and the correct inspection of liver echogenicity before any
      interpretation of high liver stiffness is recommended. We suggest that patient
      with higher level of Fibroscan score repeat it in other sides of the liver. Also,
      they should be evaluated by sonography for ruling out of possible confounders
      such as hepatic hemangioma.

PMID- 22879832
TI  - Failure of Intravenous Silibinin Monotherapy to Prevent Hepatitis C Genotype 2A
      Liver Graft Reinfection.
AB  - BACKGROUND: Hepatitis C virus (HCV) recurrence after orthotopic liver
      transplantation (OLT) remains a serious problem in the clinical management of
      post-oLT patients. Recently, two case reports have described successful
      prevention of HCV liver graft reinfection with intravenous silibinin (SIL)
      monotherapy in two carriers of genotype 3a and 1a/4 HCV. Based on these findings,
      we decided to offer such a therapy to a 65 year old woman on the oLT list. CASE
      PRESENTATION: A 65 year old patient with HCV 2a cirrhosis, a previous relapse to
      PegIFn and Rbv therapy, was listed for oLT due to hepatocellular carcinoma. She
      started SIL monotherapy 24 hours before oLT. After an initial HCV-RnA decline
      following surgery,a progressive HCV RnA increase was observed. For this reason,
      SIL was stopped after 15 days of monotherapy. CONCLUSIONS: SIL has multiple anti
      HCV mechanisms of action, most of them have been characterized in vitro only. Our
      case report shows that the antiviral effect of SIL might be HCV genotype
      dependent, as recently suggested by a study, showing no effect of SIL on the HCV
      2a subgenomic replicon model. our case reinforces the need for controlled studies
      to assess the efficacy of silibinin therapy in HCV infected patients before it
      can be broadly used in all clinical settings.

PMID- 22879833
TI  - Progression of liver diseases.

PMID- 22879834
TI  - Best practice in nurse-led chemotherapy review: a position statement from the
      United Kingdom Oncology Nursing Society.
AB  - This position statement has been formulated by nurses from the United Kingdom
      Oncology Nursing Society (UKONS) to provide guidance on the provision of nurse
      led chemotherapy review clinics for adult patients. For the purposes of this
      statement, a nurse-led chemotherapy clinic is defined as one that conducts formal
      review (in a consultation room) before the decision to proceed and prescribe the
      next cycle of chemotherapy. This statement does not address the toxicity checks
      that take place immediately prior to the administration of chemotherapy, although
      many of the same principles will apply to both settings.

PMID- 22879835
TI  - Attachment Without Fear.
AB  - John Bowlby hypothesized an attachment system that interacts with caregiving,
      exploration, and fear systems in the brain, with a particular emphasis on fear.
      Neurobiological research confirms many of his hypotheses and also raises some new
      questions. A psychological model based on this neurobiological research is
      presented here. The model extends conventional attachment theory by describing
      additional attachment processes independent of fear. In this model, the
      attachment elements of trust, openness, and dependence interact with the
      caregiving elements of caring, empathy, and responsibility.

PMID- 22879836
TI  - Heavy metals and trace elements in hair and urine of a sample of arab children
      with autistic spectrum disorder.
AB  - General information: Autism is a severe developmental disorder which involves
      social withdrawal, communication deficits, and stereotypic/repetitive behavior.
      The pathophysiological etiologies which precipitate autism symptoms remain
      elusive and controversial in many cases, but both genetic and environmental
      factors (and their interactions) have been implicated. While autism is considered
      multicausal, environmental factors have received significant attention.
      International discussion has ocused on neurotoxins such as mercury and lead,
      suggesting that these and other toxic metals contribute to the development of the
      disorder. An epidemiological study released in 2006 (Palmer et al.) linking Toxic
      Release Inventory (TRI) data on mercury to special education data in Texas
      reported a 61% increase in autism prevalence rates (or 17% adjusted) per 1000
      pounds of mercury released into the environment (1). We attempted to further
      evaluate whether exposure to variable environmental contributes to the genesis of
      autistic spectrum disorder, and thus is a factor increasing the risk for
      developing autism symptoms in utero or in early childhood. PURPOSE: The purpose
      of this study is to examine possible environmental risk factors and sources of
      exposure to mercury and other heavy metals in children with autism spectrum
      disorder versus controls. Through laboratory diagnostics we are able to
      distinguish between present and past exposure (i.e. hair analysis measurements
      reflect past exposure), urinary excretion levels of unprovoked urine represent
      immediate exposure. By assessing a spectrum of trace elements and heavy metals in
      hair and urine of both autistic and control groups, we focused on the
      participants~ past and present exposure. METHODOLOGY: The participants were 25
      Autistic Spectrum Disorder (ASD) children (22 boys and 3 girls) between the age
      of 3 and 9 years. They were either diagnosed previously by other psychiatrist,
      psychologist, and developmental pediatrician or suspected by their parents as
      being autistic. All children were attendants to the Child Psychiatric Clinic in
      Erfan Psychiatric Hospital in Jeddah, KSA. Samples were collected during the
      period of June 2006 to March 2008. A control group of 25 children without any
      psychiatric or medical disorders was age-matched and sex-matched. All parents
      signed informed consent forms. All autistic children were subjected to a full
      clinical child psychiatric sheet for the diagnosis of autism spectrum disorder
      and exclusion of other psychiatric disorders according to the Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition (DSM IV). The severity of
      autistic symptomatology was measured by the Childhood Autism Rating Scale (CARS)
      and Autism Behavior Checklist (ABC) using the Arabic versions. Both groups were
      subjected to the Questionnaire on Exposure to Heavy Metals, Physical Symptoms,
      and Child Development. Hair and baseline urine samples (i.e. unprovoked urine)
      were taken from both groups and sent to the German clinical and environmental
      laboratory Micro Trace Minerals Gmbh, for the detection of heavy metals and trace
      elements levels where metal testing was performed via ICP-MS spectroscopy
      utilizing cell technique. RESULTS: By comparing the ASD Group to the Control
      Group, we found a statistically significant difference in the mean hair levels of
      arsenic, cadmium, barium, cerium and lead (p=0.01, 0.03, 0.003, 0.003, and 0.03
      respectively), and in the mean hair levels of magnesium and zinc (p=0.001 and
      0.003 respectively). There were also statistically significant differences in the
      mean urine levels of aluminum, barium, cerium, mercury, and lead (p=0.004, 002,
      0.014, 0.006 and 0.004 respectively), and in the mean urine levels of copper and
      germanium (p=0.049 and 0.02 respectively). An agreement was found in both
      specimen (hair and urine) for barium and lead. The statistically significant
      differences in mean hair levels of arsenic, cadmium, and cerium were not
      supported by urine baseline levels. Also, the statistically significant magnesium
      and zinc levels of hair were not supported by urine levels. A disagreement was
      also found with copper and germanium concentrations.

PMID- 22879837
TI  - Hemodynamic instability after elective carotid stenting: frequency and risk
      factors.
AB  - The objective of this study is to investigate the frequency and risk factors for
      hemodynamic instability (hypotension and/or bradycardia) in response to elective
      carotid stenting and their association with neurological complications. Carotid
      artery stenting implies instrumentation of the carotid bulb where the
      baroreceptors are placed and therefore baroceptor's dysfunction may provoke
      hemodynamic instability. The study started in the Neurology Clinic of the
      Emergency University Hospital, Bucharest as a retrospective analysis of the
      charts of 130 patients (110 men with mean age of 55 years) who underwent elective
      carotid artery stenting with cerebral protection for high-grade (>70%)
      symptomatic internal carotid artery stenosis. By hemodynamic instability one can
      understand the drop in systolic blood pressure of more than 30mmHG and
      bradycardia. 20% of patients had a drop in systolic blood pressure beyond 30 mmHg
      and/or bradycardia despite an adequate fluid balance. We did't use atropine as
      premedication before carotid stenting. There was no need for aggressive
      resuscitation (dopamine) and none of the patients with bradycardia needed
      pacemaker support. Neurological complications (transient ischemic attack, minor
      stroke, major stroke) occurred in 9% of patients and were not significantly
      associated with hemodynamic instability. Extensive carotid artery manipulation, a
      long stenosis situated at the bifurcation and the prior use of beta-blockers were
      associated with an increased adjusted risk for hypotension or bradycardia.
      Hemodynamic instability due to hypotension and bradycardia in response to carotid
      artery stenting occurs in a relatively low proportion of patients. Patients who
      had a long (over 6 mm) stenosis situated near the common carotid artery's
      bifurcation and therefore underwent extensive carotid manipulation or those who
      were on beta-blockers were at high risk for hypotension or bradycardia. The
      preadministrations of intravenous fluids didn't prevent the periprocedural
      hypotensive response.

PMID- 22879838
TI  - Minimally invasive surgical treatment of malignant pleural effusions.
AB  - INTRODUCTION: Usually the pleural cavity contains a small amount of liquid
      (approximately 10 ml). Pleural effusions appear when the liquid production rate
      overpasses the absorption rate with a greater amount of liquid inside the pleural
      cavity. MATERIAL AND METHOD: Between January 1998 to December 2008 we conducted a
      study in order to establish the adequate surgical treatment for MPEs. Effective
      control of a recurrent malignant pleural effusion can greatly improve the quality
      of life of the cancer patient. The present review collects and examines the
      clinical results of minimally invasive techniques designed to treat this problem.
      RESULTS AND DISCUSSION: Patients with MPEs were studied according to several
      criteria. In our study we observed the superiority of intraoperative talc
      poudrage, probably due to a more uniform distribution of talc particles over the
      pleural surface. Minimal pleurotomy with thoracic drainage and instillation of a
      talc suspension is also a safe and effective technique and should be employed
      when there are contraindications for the thoracoscopic minimally invasive
      procedure. CONCLUSIONS: On the basis of comparisons involving effectiveness,
      morbidity, and convenience, we recommend the thoracoscopic insufflations of talc
      as a fine powder with pleural drainage as the procedure of choice.

PMID- 22879839
TI  - Gynecological Cancer Age Groups at the "Dr. Salvator Vuia" Clinical Obstetrics
      and Gynecology Hospital during the 2000-2009 Period.
AB  - OBJECTIVES: The purpose of this study is to statistically compare the mean ages
      of the patients with gynecologic cancer in our hospital during the 2000-2009
      interval. MATERIAL AND METHODS: The data was collected from the Histopathology
      Exams (HPE) registers. RESULTS: Gynecologic cancer was discovered in 1244 cases:
      731 cervical cancers, 392 uterine cancers, 82 ovarian cancers, 31 vulvar cancers
      and eight vaginal cancers.The mean ages were 52.94+/-12.96 years for cervical
      cancer (age range 22-87 years), 61.71+/-9.06 years for uterine cancer (age range
      38-85 years), 51.46+/-14.28 years for ovarian cancer (age range 18-77 years), and
      65.90+/-9.65 years for vulvar cancer (age range 39-81 years).After performing
      Student's test, the statistically significant differences were: cervical vs
      uterine (p<0.000001), cervical vs vulvar (<0.000001), uterine vs ovarian
      (<0.000001), uterine vs vulvar (<0.05), and ovarian vs vulvar (p=0.000001).
      Cervical and ovarian cancer mean ages were not significantly different (p=0.33).
      CONCLUSIONS: The mean ages of the patients from the groups with five
      gynecological cancer types from our study are similar to those in literature.
      Existing screening measures must be applied and new ones must be implemented in
      order to reduce the burden of gynaecological cancers.

PMID- 22879840
TI  - Programming an optimal atrioventricular interval in a dual chamber pacemaker
      regional population.
AB  - BACKGROUND: Since the introduction of the dual chamber pacemaker (DDDR) in the
      early 1980s, researchers have repeatedly discussed and attempted to optimize the
      atrioventricular (AV) interval, in order to increase the cardiac performance of
      pacemaker patients. Nominal AV delay in a DDDR is not, by hemodynamics, the best
      option for the majority of patients with AV conduction disorders. Our research is
      suggesting a simplified approach to define an optimal AV delay in a DDDR
      pacemaker population on the use of the programming electrocardiogram (ECG) at
      follow-up. METHODS: The study enrolled 55 consecutive patients (67.28 +/- 1.03
      years, 36 male) with an initial dual chamber pacemaker implanted for complete and
      second degree AV block between 2005-2010. Optimal AV delay was achieved by
      programming an additional delay of 95 ms, to the medium value of the interval
      between atrial pacing spike to the end of P wave or to the width of intrinsic P
      wave, on the ECG of the programming device. At discharge, shortly after the
      implant procedure, the patients were examined by Doppler echocardiography, during
      nominal and optimal AV delay pacing measuring systolic and diastolic left
      ventricular function parameters. RESULTS: Compared with the nominal AV delay
      settings, the left ventricular end diastolic volume did not changed (from 112.3
      +/- 2.3 ml to 112.9 +/- 2.3 ml), the end systolic volume decreased (from 59.8 +/-
      1.7 ml to 50.9 +/- 1.3 ml, p<0.01) after adjusted the AV delay, followed by an
      increased left ventricle ejection fraction (from 61.07 +/- 0.18 % to 65.46 +/-
      0.13 %, p<0.001) and isovolumic relaxation time decreased (from 102.7 +/- 1.9 ms
      to 97 +/- 2 ms, p<0.05). E wave velocity, A wave velocity and E/A ratio were not
      significantly changed. CONCLUSION: AV delay adjusted by programmer ECG in a
      follow-up session of an implantable device is a simple and useful method used in
      our laboratory as a resource for ventricular pacing optimization and hemodynamic
      improvement in patients with a dual chamber pacemaker (DDDR).

PMID- 22879841
TI  - Contact dermatitis - epidemiological study.
AB  - AIM: To evaluate the real incidence of contact dermatitis, to identify the most
      common allergens, the favoring factors, to establish the prophylaxis methods, the
      key for a correct management of the patient with contact dermatitis. METHOD: A
      retrospective study, on the patients that refers to the Dermatology Clinic, "St.
      Spiridon" Emergency Hospital Iasi, between 01.01.2006 and 31.12. 2009, based on
      demographic items, the type of contact dermatitis and the allergens implicated.
      RESULTS: we enrolled 353 patients between 2006-2009, representing 3,89% from the
      hospitalized patients; the study reveals a higher incidence at women (60,27%),
      similar with data from literature; the majority of the patients was aged over 45,
      with the higher rate in the interval of 45-65 years old; the most frequent
      implicated allergens and irritants were plants (26,31% - 92 patients) and topical
      drugs and antiseptics (25,65% - 89 patients); the area most affected was the face
      (25%) and the hands (19,07%), from which almost 80-90% was occupational
      dermatitis. The distribution of cases depending on the type of contact dermatitis
      indicates an approximate percentage of those allergic to those irritant.
      CONCLUSIONS: The real prevalence of this disease is unknown, being frequently a
      missed diagnosis (other kinds of eczema), the key of the correct diagnose being a
      repeated, exhaustive anamnesis, revealing all the favoring conditions and
      possible contact allergens.

PMID- 22879842
TI  - Differentiation of benign from malignant induced ascites by measuring gallbladder
      wall thickness.
AB  - INTRODUCTION: There are multiple causes for ascites and conventional diagnostic
      method for most of them is paracentesis. This method is invasive and time
      consuming. The aim of this study is to survey the reliability of measuring
      gallbladder wall thickness to discriminate between cirrhotic and malignant
      ascites. MATERIALS AND METHODS: In our study we measured the gallbladder wall
      thickness by ultrasonography in 100 consecutive patients with portal hypertension
      induced ascites and in 100 consecutive patients with peritoneal carcinomatosis
      induced ascites. RESULTS: The mean Gallbladder wall thickness was 3.94+/-0.69 mm
      in cirrhotic patients and 2.26+/-0.62 mm in patients with peritoneal
      carcinomatosis. Gallbladder wall thickening in cirrhotic patients was
      significantly more compared to patients with peritoneal carcinomatosis (p
      value=0.001). CONCLUSION: This study shows that the thickened gallbladder wall in
      patients with ascites is highly predictive for diagnosis of portal hypertension
      induced ascites.

PMID- 22879843
TI  - Particular clinical and therapeutical aspects in acute myeloid leukemia in
      elderly patients.

PMID- 22879844
TI  - Endocarditis in the 21(st) Century.
AB  - Endocarditis still carries a poor prognosis despite improvement in preventive
      strategies and advances in diagnosis and also in treatment. Epidemiology of
      infective endocarditis (IE) has changed in late years. Contemporary antibiotic
      overuse determines antibiotic resistance against microorganisms involved in IE.
      Prophylaxis principles have been changed and restricted in order to avoid
      excessive antibiotic use and unfounded costs. Current guidelines are often based
      on expert opinion because of the low incidence of the disease, the absence of
      randomized trials, and the limited number of meta-analyses. The present review
      will focus on current changes in epidemiology, prophylaxis, diagnosis and
      treatment options.

PMID- 22879845
TI  - Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney
      Disease and Clinical Usefulness of Their Assessment Using a Non-invasive
      Technique - Skin Autofluorescence.
AB  - Accelerated formation and accumulation of advanced glycation end-products occur
      under circumstances of increased supply of substrates such as hyperglycaemic or
      oxidative stress and in age-related and chronic diseases like diabetes mellitus,
      chronic renal failure, neurodegenerative diseases, osteoarthritis and also non
      diabetic atherosclerosis and chronic heart failure. Advanced glycation end
      products accumulation occurs especially on long-lived proteins such as collagen
      in the skin and in vascular basement membranes leading to vascular damage.
      Adequate renal clearance capacity is an important factor in the effective removal
      of advanced glycation end-products. The Autofluorescence Reader was developed as
      a marker, representative for tissue advanced glycation end-products accumulation,
      easily applicable in a clinical setting, initially for predicting diabetes
      related complications. Studies have already shown a relationship between skin
      autofluorescence and diabetes complications, as well as its predictive value for
      total and cardiovascular mortality in type 2 diabetes. Moreover skin
      autofluorescence was demonstrated to be superior to Haemoglobin A1c and other
      conventional risk factors. Advanced glycation end-products have been proposed as
      a novel factor involved in the development and progression of chronic heart
      failure. Assessment of advanced glycation end-products accumulation in end-stage
      renal disease and undergoing renal replacement therapies patients has become of
      great importance. Cardiovascular and connective tissue disorders are very common
      in patients with end-stage renal disease, and the accumulation of advanced
      glycation end-products is significantly increased in these patients. Mortality is
      markedly increased in patients with decreased kidney function, particularly in
      patients with end-stage renal disease. Skin advanced glycation end-products
      levels are strong predictors of survival in haemodialysis patients independent of
      other established risk factors. The Autofluorescence Reader may be useful as a
      clinical tool for rapid assessment of risk for advanced glycation end-products
      related long-term complications, not only in diabetes, but in other conditions
      associated with advanced glycation end-products accumulation as well.

PMID- 22879846
TI  - Sentinel lymph node - work hypothesis in sinonasal carcinoma treatment.
AB  - Although rare, sinonasal malignancies (SNM) can be lesions of immense importance.
      Approximately 60-70% of sinonasal malignancies (SNM) occur in the maxillary sinus
      and 20-30% occurs in the nasal cavity itself. The lymphatic drainage of the
      sinuses and nasal cavity include levels I-III as well as the parapharyngian
      nodes. Elective regional lymph node dissections became controversial because of
      overtreatment of the many patients without lymph node metastases. Lymphatic
      metastasis is the most important mechanism of spread in sinonasal squamous cell
      carcinoma considering the vast network of vessels in this area. The indications
      and type of neck dissection to be performed in the positive node neck and
      management of the N0 neck remain controversial. The sentinel lymph node concept
      is based on the Halsted theory that stressed the importance of locoregional
      cancer treatment because of the far site spread. Each patient with head and neck
      malignancies, including sinonasal carcinoma have about 2-3 sentinel lymph nodes
      of which up to 40% of them contain metastases.

PMID- 22879847
TI  - The burden of cancer attributable to alcohol consumption.
AB  - Many epidemiological studies have demonstrated a correlation between alcohol
      intake and the occurrence of cancer in humans. All types of alcoholic beverages
      are associated with an increased risk which suggests that ethanol itself is the
      crucial compound which causes that effect.The International Agency for Research
      for Cancer classified alcohol consumption and acetaldehyde associated with
      alcohol consumption as carcinogenic for humans (group 1): oral cavity, pharynx,
      larynx, esophagus, colorectal, liver and female breast.THE MECHANISMS BY WHICH
      ALCOHOL CONSUMPTION EXERTS ITS CARCINOGENIC EFFECT HAVE NOT BEEN DEFINED FULLY,
      ALTHOUGH PLAUSIBLE EVENTS INCLUDE: a genotoxic effect of acetaldehyde; increased
      estrogen concentration, which is important for breast carcinogenesis; a role as
      solvent of tobacco carcinogens; production of reactive oxygen species and
      nitrogen species; and change in folate metabolism.Most alcohol-induced diseases
      increases in a linear fashion as intake increases: oral, esophagus and colon
      cancer fall into this pattern: very little is known about safe margins of alcohol
      consumption. Given the linear dose-response relation between alcohol intake and
      risk of cancer, control of heavy drinking remains the main target for cancer
      control.In healthy subjects, European Code Against Cancer recommends keeping
      daily consumption within two drinks for man and one drink for women.In our
      opinion, there are not enough data to support the actually safe intake of
      alcohol. Any level of alcohol consumption increase the risk of developing an
      alcohol related cancer. The level of risk increases in line with the level
      consumption.

PMID- 22879848
TI  - "Amyand's Hernia" - Pathophysiology, Role of Investigations and Treatment.
AB  - BACKGROUND: In the present era, appendicitis and hernia are common problems but
      their presentations in different positions are rare to be seen. It is difficult
      to make diagnose pre-operatively of contents as appendicitis in obstructed
      hernia. The term "Amyand's hernia" was lost in the literature and we are
      describing its pathophysiology and management. The aggravating factors are:
      complex injuries related to hernia (size, degree of sliding, multiplicity, etc.),
      patient characteristics (age, activity, respiratory disease, dysuria, obesity,
      constipation). If not treated in the earliest stages then it can lead to
      significant morbidity and mortality. Existing literature describes almost
      exclusively its pathophysiology, investigations and treatment. MATERIAL AND
      METHODS: We have focused on clinical presentation, radiological investigations
      and management of "Amyand's hernia". In literature, there is still confusion
      regarding investigations and treatment. We are presenting such rare entity
      managed in time without encountering any post-operative complications. RESULTS:
      Ultrasonography and Computed Tomography are useful tests but clinical correlation
      is necessary in incarcerated appendix. Regarding treatment, it is clear that if
      appendix is inflamed then it should be removed, but we concluded that if appendix
      is found to be normal in obstructed hernia then it should also be removed due to
      possible later inflammation. CONCLUSION: If the appendix found in the hernial sac
      is inflamed then chances of mortality increase. Although emergency surgery is
      indicated in all obstructed hernias, morbidity and mortality can be decreased if
      operated on time. Early recognition and its awareness, along with good surgical
      technique in such cases are keys to success when dealing with this problem.

PMID- 22879849
TI  - Conventional curettage adenoidectomy versus endoscopic assisted adenoidectomy.

PMID- 22879850
TI  - Manifestations of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic, multifaceted autoimmune
      inflammatory disease that can affect any part of the body. SLE is a disease of
      unknown aetiology with a variety of presenting features and manifestations.
      Interest in the disease has been stimulated in recent years, and improved methods
      of diagnosis have resulted in a significant increase in the number of cases
      recognized. It is apparent that it can no longer be regarded as a rare disease.
      The majority of the pathology in SLE is related to deposits of immune complexes
      in various organs, which triggers complement and other mediators of inflammation.
      Symptoms vary from person to person, and may come and go, depend on what part of
      the body is affected, can be mild, moderate, or severe. Diagnosis can be
      difficult because lupus mimics many other diseases; it requires clinical and
      serologic criteria.

PMID- 22879851
TI  - Update in infectious diseases.

PMID- 22879852
TI  - Update in Pneumology - Focus on Asthma and COPD.

PMID- 22879853
TI  - Update in diabetology.

PMID- 22879854
TI  - What's New in Histological Transformation of Indolent Lymphomas?

PMID- 22879855
TI  - Update in neurosurgery - nanotechnology in neurosurgery.

PMID- 22879856
TI  - The importance of social support for people with type 2 diabetes - a qualitative
      study with general practitioners, practice nurses and patients.
AB  - OBJECTIVE: Social support is an important element of family medicine within a
      primary care setting, delivered by general practitioners and practice nurses in
      addition to usual clinical care. The aim of the study was to explore general
      practitioner's, practice nurse's and people with type 2 diabetes' views,
      experiences and perspectives of the importance of social support in caring for
      people with type 2 diabetes and their role in providing social support. METHODS:
      Interviews with general practitioners (n=10) and focus groups with practice
      nurses (n=10) and people with diabetes (n=9). All data were audio-recorded, fully
      transcribed and thematically analysed using qualitative content analysis by
      Mayring. RESULTS: All participants emphasized the importance of the concept of
      social support and its impacts on well-being of people with type 2 diabetes.
      Social support is perceived helpful for people with diabetes in order to improve
      diabetes control and give support for changes in lifestyle habits (physical
      activity and dietary changes). General practitioners identified a lack of
      information about facilities in the community like sports or self-help groups.
      Practice nurses emphasized that they need more training, such as in dietary
      counselling. CONCLUSIONS: Social support given by general practitioners and
      practice nurses plays a crucial role for people with type 2 diabetes and is an
      additional component of social care. However there is a need for an increased
      awareness by general practitioners and practice nurses about the influence social
      support could have on the individual's diabetes management.

PMID- 22879857
TI  - Sex-specific predictor analyses for the incidence of recurrent headaches in
      German schoolchildren.
AB  - OBJECTIVE: The aim of the present study was to identify psychosocial risk factors
      for the incidence of recurrent headache (HA) in children/adolescents (8-15
      years). METHOD: In 2003 (Wave 1) a representative, population-based sample of
      8800 parents was mailed a questionnaire. Those who took part were asked to
      participate again one year later (Wave 2). Of the parents originally contacted,
      47.3% participated in both surveys. Potential risk factors concerning the areas
      'school' and 'emotional and behavioural problems' were collected in Wave 1.
      Binary logistic regression analyses were performed to assess their predictive
      value for HA in Wave 2. RESULTS: Univariable regression analyses showed that for
      boys and girls most of the predictor variables influenced the incidence of
      recurrent HA, but only to a very low extent. When all variables were assessed
      jointly in a multivariable model, these factors lost their predictive power for
      boys. For girls, 'academic problems' and 'dysfunctional stress coping' were shown
      to increase the chance for the incidence of recurrent HA. DISCUSSION: In contrast
      to previous findings, school-related factors and emotional and behavioural
      problems failed to predict HA in boys, and only two factors appeared relevant
      with regard to girls. This might be due to the strict unidirectional design,
      which focussed exclusively on the incidence of HA.

PMID- 22879864
TI  - Crystal structures of human pyridoxal kinase in complex with the neurotoxins,
      ginkgotoxin and theophylline: insights into pyridoxal kinase inhibition.
AB  - Several drugs and natural compounds are known to be highly neurotoxic, triggering
      epileptic convulsions or seizures, and causing headaches, agitations, as well as
      other neuronal symptoms. The neurotoxic effects of some of these compounds,
      including theophylline and ginkgotoxin, have been traced to their inhibitory
      activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of
      the active cofactor form of vitamin B6, pyridoxal 5'-phosphate (PLP). Pyridoxal
      (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the
      B6 vitamer required as a cofactor for over 160 enzymatic activities essential in
      primary and secondary metabolism. We have performed structural and kinetic
      studies on hPL kinase with several potential inhibitors, including ginkgotoxin
      and theophylline. The structural studies show ginkgotoxin and theophylline bound
      at the substrate site, and are involved in similar protein interactions as the
      natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin
      is also observed bound at the active site. This work provides insights into the
      molecular basis of hPL kinase inhibition and may provide a working hypothesis to
      quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors.
      Such adverse effects may be prevented by administration of an appropriate form of
      vitamin B6, or provide clues of how to modify these drugs to help reduce their
      hPL kinase inhibitory effects.

PMID- 22879858
TI  - Smoking cessation increases short-term risk of type 2 diabetes irrespective of
      weight gain: the Japan Public Health Center-Based Prospective Study.
AB  - OBJECTIVE: The effect of smoking cessation on the risk of diabetes has been
      reported previously. However, it is unknown whether the association is influenced
      by weight gain and other potential risk factors. METHODS: The Japan Public Health
      Center-Based Prospective Study established in 1990 for Cohort I and in 1993 for
      Cohort II provided data, and 25,875 men and 33,959 women were analyzed. The
      response rate to the baseline questionnaire was 80.9%, and 68.4% of the
      respondents participated both the 5- and 10-year follow-up surveys. Smoking
      cessation was noted during the initial five years and the development of diabetes
      was reported in the subsequent five years. RESULTS: An increased risk was
      observed among individuals who newly quit smoking compared with never smokers
      among men (odds ratio (OR)=1.42, 95% CI=1.03-1.94) and women (OR=2.84, CI=1.53
      5.29). The risk of developing diabetes among male new quitters who gained 3 kg or
      more during the 5-year follow-up did not substantially differ from the risk among
      male never smokers with less than 3 kg of weight gain or no weight gain, while an
      increased risk was observed among male new quitters with less or no weight gain
      (OR=1.46, 95%CI 1.00-2.14). An insignificant increased risk was observed among
      male new quitters with a family history of diabetes compared with male never
      smokers with a family history of diabetes. The risk was more than twice as high
      for male new quitters who used to smoke 25 or more cigarettes per day compared
      with never smokers (OR=2.15, 95%CI: 1.34-3.47). DISCUSSION: An increased risk of
      diabetes was implied among individuals who quit smoking. However, the increased
      risk was not implied among those who gained weight over the 5-years of follow-up.
      Those who had major risk factors for diabetes or who smoked heavier had a higher
      risk.

PMID- 22879865
TI  - Functional analysis of two PLA2G2A variants associated with secretory
      phospholipase A2-IIA levels.
AB  - BACKGROUND: Secretory phospholipase A2 group IIA (sPLA2-IIA) has been identified
      as a biomarker of atherosclerosis in observational and animal studies. The
      protein is encoded by the PLA2G2A gene and the aim of this study was to test the
      functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G
      where the rare alleles have been previously associated with higher and lower
      sPLA2-IIA levels respectively. METHODOLOGY/PRINCIPAL FINDINGS: Luciferase assays,
      electrophoretic mobility shift assays (EMSA), and RNA expression by RT-PCR were
      used to examine allelic differences. For rs3767221 the G allele showed ~55% lower
      luciferase activity compared to the T allele (T = 62.1 (95% CI 59.1 to 65.1) G =
      27.8 (95% CI 25.0 to 30.6), p = 1.22*10-35, and stronger EMSA binding of a
      nuclear protein compared to the T-allele. For rs11573156 C >G there were no
      luciferase or EMSA allelic differences seen. In lymphocyte cell RNA, from
      individuals of known rs11573156 genotype, there was no allelic RNA expression
      difference for exons 5 and 6, but G allele carriers (n = 7) showed a trend to
      lower exon 1-2 expression compared to CC individuals. To take this further, in
      the ASAP study (n = 223), an rs11573156 proxy (r2 = 0.91) showed ~25% higher
      liver expression of PLA2G2A (1.67*10-17) associated with the G allele. However,
      considering exon specific expression, the association was greatly reduced for
      exon 2 (4.5*10-5) compared to exons 3-6 (10-10 to 10-20), suggesting rs11573156 G
      allele-specific exon 2 skipping. CONCLUSION: Both SNPs are functional and provide
      useful tools for Mendelian Randomisation to determine whether the relationship
      between sPLA2-IIA and coronary heart disease is causal.

PMID- 22879872
TI  - Selective small molecule Stat3 inhibitor reduces breast cancer tumor-initiating
      cells and improves recurrence free survival in a human-xenograft model.
AB  - Metastasis and disease relapse are hypothesized to result from tumor initiating
      cells (TICs). Previously, we have defined a CD44+/CD24-/low mammosphere-forming
      tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a
      critical node in self-renewal based on an ongoing lentiviral shRNA screen being
      conducted in two breast cancer cell lines SUM159 and BT549. In corroborating
      work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the
      percentage of cells expressing TIC markers (CD44+/CD24-/low and ALDH+) and
      mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in
      SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day
      recurrence-free survival relative to docetaxel alone with the addition of the
      Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a
      strong impetus for the development of selective Stat3 inhibitors in order to
      improve survival in patients with p-Stat3 overexpressing tumors.

PMID- 22879873
TI  - Salt marsh as a coastal filter for the oceans: changes in function with
      experimental increases in nitrogen loading and sea-level rise.
AB  - Coastal salt marshes are among Earth's most productive ecosystems and provide a
      number of ecosystem services, including interception of watershed-derived
      nitrogen (N) before it reaches nearshore oceans. Nitrogen pollution and climate
      change are two dominant drivers of global-change impacts on ecosystems, yet their
      interacting effects at the land-sea interface are poorly understood. We addressed
      how sea-level rise and anthropogenic N additions affect the salt marsh ecosystem
      process of nitrogen uptake using a field-based, manipulative experiment. We
      crossed simulated sea-level change and ammonium-nitrate (NH(4)NO(3))-addition
      treatments in a fully factorial design to examine their potentially interacting
      effects on emergent marsh plants in a central California estuary. We measured
      above- and belowground biomass and tissue nutrient concentrations seasonally and
      found that N-addition had a significant, positive effect on a) aboveground
      biomass, b) plant tissue N concentrations, c) N stock sequestered in plants, and
      d) shoot:root ratios in summer. Relative sea-level rise did not significantly
      affect biomass, with the exception of the most extreme sea-level-rise simulation,
      in which all plants died by the summer of the second year. Although there was a
      strong response to N-addition treatments, salt marsh responses varied by season.
      Our results suggest that in our site at Coyote Marsh, Elkhorn Slough, coastal
      salt marsh plants serve as a robust N trap and coastal filter; this function is
      not saturated by high background annual N inputs from upstream agriculture.
      However, if the marsh is drowned by rising seas, as in our most extreme sea-level
      rise treatment, marsh plants will no longer provide the ecosystem service of
      buffering the coastal ocean from eutrophication.

PMID- 22879874
TI  - Innate defense regulator peptide 1018 in wound healing and wound infection.
AB  - Innate defense regulators (IDRs) are synthetic immunomodulatory versions of
      natural host defense peptides (HDP). IDRs mediate protection against bacterial
      challenge in the absence of direct antimicrobial activity, representing a novel
      approach to anti-infective and anti-inflammatory therapy. Previously, we reported
      that IDR-1018 selectively induced chemokine responses and suppressed pro
      inflammatory responses. As there has been an increasing appreciation for the
      ability of HDPs to modulate complex immune processes, including wound healing, we
      characterized the wound healing activities of IDR-1018 in vitro. Further, we
      investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing
      models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP
      derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic
      in vitro as compared to either LL-37 or HB-107. Furthermore, administration of
      IDR-1018 resulted in a dose-dependent increase in fibroblast cellular
      respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound
      healing in S. aureus infected porcine and non-diabetic but not in diabetic murine
      wounds. However, no significant differences in bacterial colonization were
      observed. Our investigation demonstrates that in addition to previously reported
      immunomodulatory activities IDR-1018 promotes wound healing independent of direct
      antibacterial activity. Interestingly, these effects were not observed in
      diabetic wounds. It is anticipated that the wound healing activities of IDR-1018
      can be attributed to modulation of host immune pathways that are suppressed in
      diabetic wounds and provide further evidence of the multiple immunomodulatory
      activities of IDR-1018.

PMID- 22879875
TI  - Computational selection of transcriptomics experiments improves Guilt-by
      Association analyses.
AB  - The Guilt-by-Association (GBA) principle, according to which genes with similar
      expression profiles are functionally associated, is widely applied for functional
      analyses using large heterogeneous collections of transcriptomics data. However,
      the use of such large collections could hamper GBA functional analysis for genes
      whose expression is condition specific. In these cases a smaller set of condition
      related experiments should instead be used, but identifying such functionally
      relevant experiments from large collections based on literature knowledge alone
      is an impractical task. We begin this paper by analyzing, both from a
      mathematical and a biological point of view, why only condition specific
      experiments should be used in GBA functional analysis. We are able to show that
      this phenomenon is independent of the functional categorization scheme and of the
      organisms being analyzed. We then present a semi-supervised algorithm that can
      select functionally relevant experiments from large collections of
      transcriptomics experiments. Our algorithm is able to select experiments relevant
      to a given GO term, MIPS FunCat term or even KEGG pathways. We extensively test
      our algorithm on large dataset collections for yeast and Arabidopsis. We
      demonstrate that: using the selected experiments there is a statistically
      significant improvement in correlation between genes in the functional category
      of interest; the selected experiments improve GBA-based gene function prediction;
      the effectiveness of the selected experiments increases with annotation
      specificity; our algorithm can be successfully applied to GBA-based pathway
      reconstruction. Importantly, the set of experiments selected by the algorithm
      reflects the existing literature knowledge about the experiments. [A MATLAB
      implementation of the algorithm and all the data used in this paper can be
      downloaded from the paper website: http://www.paccanarolab.org/papers/CorrGene/].

PMID- 22879876
TI  - The chronotron: a neuron that learns to fire temporally precise spike patterns.
AB  - In many cases, neurons process information carried by the precise timings of
      spikes. Here we show how neurons can learn to generate specific temporally
      precise output spikes in response to input patterns of spikes having precise
      timings, thus processing and memorizing information that is entirely temporally
      coded, both as input and as output. We introduce two new supervised learning
      rules for spiking neurons with temporal coding of information (chronotrons), one
      that provides high memory capacity (E-learning), and one that has a higher
      biological plausibility (I-learning). With I-learning, the neuron learns to fire
      the target spike trains through synaptic changes that are proportional to the
      synaptic currents at the timings of real and target output spikes. We study these
      learning rules in computer simulations where we train integrate-and-fire neurons.
      Both learning rules allow neurons to fire at the desired timings, with sub
      millisecond precision. We show how chronotrons can learn to classify their
      inputs, by firing identical, temporally precise spike trains for different inputs
      belonging to the same class. When the input is noisy, the classification also
      leads to noise reduction. We compute lower bounds for the memory capacity of
      chronotrons and explore the influence of various parameters on chronotrons'
      performance. The chronotrons can model neurons that encode information in the
      time of the first spike relative to the onset of salient stimuli or neurons in
      oscillatory networks that encode information in the phases of spikes relative to
      the background oscillation. Our results show that firing one spike per cycle
      optimizes memory capacity in neurons encoding information in the phase of firing
      relative to a background rhythm.

PMID- 22879877
TI  - Genomic aberrations in an African American colorectal cancer cohort reveals a MSI
      specific profile and chromosome X amplification in male patients.
AB  - OBJECTIVE: DNA aberrations that cause colorectal cancer (CRC) occur in multiple
      steps that involve microsatellite instability (MSI) and chromosomal instability
      (CIN). Herein, we studied CRCs from AA patients for their CIN and MSI status.
      EXPERIMENTAL DESIGN: Array CGH was performed on 30 AA colon tumors. The MSI
      status was established. The CGH data from AA were compared to published lists of
      41 TSG and oncogenes in Caucasians and 68 cancer genes, proposed via systematic
      sequencing for somatic mutations in colon and breast tumors. The patient-by
      patient CGH profiles were organized into a maximum parsimony cladogram to give
      insights into the tumors' aberrations lineage. RESULTS: The CGH analysis revealed
      that CIN was independent of age, gender, stage or location. However, both the
      number and nature of aberrations seem to depend on the MSI status. MSI-H tumors
      clustered together in the cladogram. The chromosomes with the highest rates of
      CGH aberrations were 3, 5, 7, 8, 20 and X. Chromosome X was primarily amplified
      in male patients. A comparison with Caucasians revealed an overall similar
      aberration profile with few exceptions for the following genes; THRB, RAF1, LPL,
      DCC, XIST, PCNT, STS and genes on the 20q12-q13 cytoband. Among the 68 CAN genes,
      all showed some level of alteration in our cohort. CONCLUSION: Chromosome X
      amplification in male patients with CRC merits follow-up. The observed CIN may
      play a distinctive role in CRC in AAs. The clustering of MSI-H tumors in global
      CGH data analysis suggests that chromosomal aberrations are not random.

PMID- 22879878
TI  - Transmitted antiretroviral drug resistance in New York State, 2006-2008: results
      from a new surveillance system.
AB  - BACKGROUND: HIV transmitted drug resistance (TDR) is a public health concern
      because it has the potential to compromise antiretroviral therapy (ART) at the
      population level. In New York State, high prevalence of TDR in a local cohort and
      a multiclass resistant case cluster led to the development and implementation of
      a statewide resistance surveillance system. METHODOLOGY: We conducted a cross
      sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed
      and reported in New York State between 2006 and 2008, including 4,155 with HIV
      genotypes drawn within 3 months of initial diagnosis and electronically reported
      to the new resistance surveillance system. We assessed compliance with DHHS
      recommendations for genotypic resistance testing and estimated TDR among new HIV
      diagnoses. PRINCIPAL FINDINGS: Of 13,109 new HIV diagnoses, 9,785 (75%) had
      laboratory evidence of utilization of HIV-related medical care, and 4,155 (43%)
      had a genotype performed within 3 months of initial diagnosis. Of these, 11.2%
      (95% confidence interval [CI], 10.2%-12.1%) had any evidence of TDR. The
      proportion with mutations associated with any antiretroviral agent in the NNRTI,
      NRTI or PI class was 6.3% (5.5%-7.0%), 4.3% (3.6%-4.9%) and 2.9% (2.4%-3.4%),
      respectively. Multiclass resistance was observed in <1%. TDR did not increase
      significantly over time (p for trend = 0.204). Men who have sex with men were not
      more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77
      1.30)). TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%-7.9%) and
      1.4% (1.0%-1.8%), respectively. CONCLUSIONS/SIGNIFICANCE: TDR appears to be
      evenly distributed and stable among new HIV diagnoses in New York State;
      multiclass TDR is rare. Less than half of new diagnoses initiating care received
      a genotype per DHHS guidelines.

PMID- 22879879
TI  - Stochastic amplification of fluctuations in cortical up-states.
AB  - Cortical neurons are bistable; as a consequence their local field potentials can
      fluctuate between quiescent and active states, generating slow 0.5 2 Hz
      oscillations which are widely known as transitions between Up and Down States.
      Despite a large number of studies on Up-Down transitions, deciphering its nature,
      mechanisms and function are still today challenging tasks. In this paper we focus
      on recent experimental evidence, showing that a class of spontaneous oscillations
      can emerge within the Up states. In particular, a non-trivial peak around 20 Hz
      appears in their associated power-spectra, what produces an enhancement of the
      activity power for higher frequencies (in the 30-90 Hz band). Moreover, this
      rhythm within Ups seems to be an emergent or collective phenomenon given that
      individual neurons do not lock to it as they remain mostly unsynchronized.
      Remarkably, similar oscillations (and the concomitant peak in the spectrum) do
      not appear in the Down states. Here we shed light on these findings by using
      different computational models for the dynamics of cortical networks in presence
      of different levels of physiological complexity. Our conclusion, supported by
      both theory and simulations, is that the collective phenomenon of "stochastic
      amplification of fluctuations"--previously described in other contexts such as
      Ecology and Epidemiology--explains in an elegant and parsimonious manner, beyond
      model-dependent details, this extra-rhythm emerging only in the Up states but not
      in the Downs.

PMID- 22879881
TI  - Performance of two Southern California benthic community condition indices using
      species abundance and presence-only data: relevance to DNA barcoding.
AB  - DNA barcoding, as it is currently employed, enhances use of marine benthic
      macrofauna as environmental condition indicators by improving the speed and
      accuracy of the underlying taxonomic identifications. The next generation of
      barcoding applications, processing bulk environmental samples, will likely only
      provide presence information. However, macrofauna indices presently used to
      interpret these data are based on species abundances. To assess the importance of
      this difference, we evaluated the performance of the Southern California Benthic
      Response Index (BRI) and the AZTI Marine Biotic Index (AMBI) when species
      abundance data were removed from their calculation. Presence only versions of
      these two indices were created by eliminating abundance weighting while
      preserving species identity. Associations between the presence and abundance BRI,
      and the presence and abundance AMBI were highly significant, with correlation
      coefficients of 0.99 and 0.81, respectively. The presence versions validated
      almost equally to the abundance-based indices when applied to the spatial and the
      temporal monitoring data used to validate the original indices. Simulations in
      which taxa were systematically removed from calculation of the indices were also
      conducted to assess how large the barcode library must be for the indices to be
      effective. Correlation between the BRI-P and BRI remained above 0.9 with only 370
      species in the library and reducing the number of species to 450 had almost no
      effect on correlation between the presence and abundance versions of the AMBI.

PMID- 22879880
TI  - Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell
      proliferation and differentiation.
AB  - Retinoic acid (RA) can induce growth arrest and neuronal differentiation of
      neuroblastoma cells and has been used in clinic for treatment of neuroblastoma.
      It has been reported that RA induces the expression of several HOXD genes in
      human neuroblastoma cell lines, but their roles in RA action are largely unknown.
      The HOXD cluster contains nine genes (HOXD1, HOXD3, HOXD4, and HOXD8-13) that are
      positioned sequentially from 3' to 5', with HOXD1 at the 3' end and HOXD13 the 5'
      end. Here we show that all HOXD genes are induced by RA in the human
      neuroblastoma BE(2)-C cells, with the genes located at the 3' end being activated
      generally earlier than those positioned more 5' within the cluster. Individual
      induction of HOXD8, HOXD9, HOXD10 or HOXD12 is sufficient to induce both growth
      arrest and neuronal differentiation, which is associated with downregulation of
      cell cycle-promoting genes and upregulation of neuronal differentiation genes.
      However, induction of other HOXD genes either has no effect (HOXD1) or has
      partial effects (HOXD3, HOXD4, HOXD11 and HOXD13) on BE(2)-C cell proliferation
      or differentiation. We further show that knockdown of HOXD8 expression, but not
      that of HOXD9 expression, significantly inhibits the differentiation-inducing
      activity of RA. HOXD8 directly activates the transcription of HOXC9, a key
      effector of RA action in neuroblastoma cells. These findings highlight the
      distinct functions of HOXD genes in RA induction of neuroblastoma cell
      differentiation.

PMID- 22879882
TI  - PI3K contributed to modulation of spinal nociceptive information related to
      ephrinBs/EphBs.
AB  - There is accumulating evidence to implicate the importance of EphBs receptors and
      ephrinBs ligands were involved in modulation of spinal nociceptive information.
      However, the downstream mechanisms that control this process are not well
      understood. In the present study, we investigated whether phosphatidylinositol 3
      kinase (PI3K), as the downstream effectors, participates in modulation of spinal
      nociceptive information related to ephrinBs/EphBs. Intrathecal injection of
      ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical
      hyperalgesia, accompanied by the increase of spinal PI3K-p110gamma,
      phosphorylation of AKT (p-AKT) and c-Fos expression. Pre-treatment with PI3K
      inhibitor wortmannin or LY294002 prevented activation of spinal AKT induced by
      ephrinB1-Fc. Inhibition of spinal PI3K signaling dose-dependently prevented and
      reversed pain behaviors and spinal c-Fos protein expression induced by
      intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by
      intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and
      chronic constrictive injury-induced neuropathic pain behaviors accompanied by
      decreased expression of spinal PI3K,p-AKT and c-Fos protein. Furthermore, pre
      treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc
      induced ERK activation in spinal. These data demonstrated that PI3K and PI3K
      crosstalk to ERK signaling contributed to modulation of spinal nociceptive
      information related to ephrinBs/EphBs.

PMID- 22879883
TI  - Discovery of genes related to insecticide resistance in Bactrocera dorsalis by
      functional genomic analysis of a de novo assembled transcriptome.
AB  - Insecticide resistance has recently become a critical concern for control of many
      insect pest species. Genome sequencing and global quantization of gene expression
      through analysis of the transcriptome can provide useful information relevant to
      this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of
      the world's most destructive agricultural pests, and recently it has been used as
      a target for studies of genetic mechanisms related to insecticide resistance.
      However, prior to this study, the molecular data available for this species was
      largely limited to genes identified through homology. To provide a broader pool
      of gene sequences of potential interest with regard to insecticide resistance,
      this study uses whole transcriptome analysis developed through de novo assembly
      of short reads generated by next-generation sequencing (NGS). The transcriptome
      of B. dorsalis was initially constructed using Illumina's Solexa sequencing
      technology. Qualified reads were assembled into contigs and potential splicing
      variants (isotigs). A total of 29,067 isotigs have putative homologues in the non
      redundant (nr) protein database from NCBI, and 11,073 of these correspond to
      distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546
      isotigs contain coding sequences that are at least 80% complete and appear to
      represent B. dorsalis genes. We observed a strong correlation between the
      completeness of the assembled sequences and the expression intensity of the
      transcripts. The assembled sequences were also used to identify large numbers of
      genes potentially belonging to families related to insecticide resistance. A
      total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major
      enzyme families involved in insecticide metabolism and resistance, were
      identified. In addition, 36 isotigs were discovered to contain target site
      sequences related to four classes of resistance genes. Identified sequence motifs
      were also analyzed to characterize putative polypeptide translational products
      and associate them with specific genes and protein functions.

PMID- 22879884
TI  - Human endogenous retrovirus expression is inversely associated with chronic
      immune activation in HIV-1 infection.
AB  - Human endogenous retroviruses (HERV) are remnants of ancestral retroviral
      infections integrated into the germ line, and constitute approximately 8% of the
      genome. Several autoimmune disorders, malignancies, and infectious diseases such
      as HIV-1 are associated with higher HERV expression. The degree to which HERV
      expression in vivo results in persistent inflammation is not known. We studied
      the association of immune activation and HERV-K expression in 20 subjects with
      chronic, untreated progressive HIV-1 infection and 10 HIV-1 negative controls.
      The mean HERV-K gag and env RNA expression level in the HIV-1 infected cohort was
      higher than in the control group (p = 0.0003), and was negatively correlated with
      the frequency of activated CD38+HLA-DR+CD4+ T cells (Rho = -0.61; p = 0.01) and
      activated CD38+HLA-DR+CD8+ T cells (Rho = -0.51; p = 0.03). Although HIV-infected
      persons had higher levels of HERV-K RNA expression (as expected), the level of
      RNA expression was negatively associated with level of T cell activation. The
      mechanism for this unexpected association remains to be defined.

PMID- 22879885
TI  - Metagenomic annotation networks: construction and applications.
AB  - The derivation and comparison of biological interaction networks are vital for
      understanding the functional capacity and hierarchical organization of integrated
      microbial communities. In the current work we present metagenomic annotation
      networks as a novel taxonomy-free approach for understanding the functional
      architecture of metagenomes. Specifically, metagenomic operon predictions are
      exploited to derive functional interactions that are translated and categorized
      according to their associated functional annotations. The result is a collection
      of discrete networks of weighted annotation linkages. These networks are
      subsequently examined for the occurrence of annotation modules that portray the
      functional and organizational characteristics of various microbial communities. A
      variety of network perspectives and annotation categories are applied to recover
      a diverse range of modules with different degrees of annotative cohesiveness.
      Applications to biocatalyst discovery and human health issues are discussed, as
      well as the limitations of the current implementation.

PMID- 22879886
TI  - Extracellular neural microstimulation may activate much larger regions than
      expected by simulations: a combined experimental and modeling study.
AB  - Electrical stimulation of the central nervous system has been widely used for
      decades for either fundamental research purposes or clinical treatment
      applications. Yet, very little is known regarding the spatial extent of an
      electrical stimulation. If pioneering experimental studies reported that
      activation threshold currents (TCs) increase with the square of the neuron-to
      electrode distance over a few hundreds of microns, there is no evidence that this
      quadratic law remains valid for larger distances. Moreover, nowadays, numerical
      simulation approaches have supplanted experimental studies for estimating TCs.
      However, model predictions have not yet been validated directly with experiments
      within a common paradigm. Here, we present a direct comparison between
      experimental determination and modeling prediction of TCs up to distances of
      several millimeters. First, we combined patch-clamp recording and microelectrode
      array stimulation in whole embryonic mouse spinal cords to determine TCs.
      Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but
      rather tended to remain constant for distances larger than 1 millimeter. We next
      built a combined finite element--compartment model of the same experimental
      paradigm to predict TCs. While theoretical TCs closely matched experimental TCs
      for distances <250 microns, they were highly overestimated for larger distances.
      This discrepancy remained even after modifications of the finite element model of
      the potential field, taking into account anisotropic, heterogeneous or dielectric
      properties of the tissue. In conclusion, these results show that quadratic
      evolution of TCs does not always hold for large distances between the electrode
      and the neuron and that classical models may underestimate volumes of tissue
      activated by electrical stimulation.

PMID- 22879887
TI  - Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP
      ribosylating toxins.
AB  - Among the several toxins used by pathogenic bacteria to target eukaryotic host
      cells, proteins that exert ADP-ribosylation activity represent a large and
      studied family of dangerous and potentially lethal toxins. These proteins alter
      cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to
      cellular proteins involved in key metabolic pathways. In the present study, we
      tested the capability of four of these toxins, to ADP-ribosylate alpha- and beta-
      defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin
      (LT) from Escherichia coli both modified the human alpha-defensin (HNP-1) and
      beta- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP
      ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP
      1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate
      but it was completely inactive on HBD1. On the other hand, HNP-1 strongly
      influenced NarE inhibiting its transferase activity while enhancing auto-ADP
      ribosylation. We conclude that only some arginine-specific ADP-ribosylating
      toxins recognize defensins as substrates in vitro. Modifications that alter the
      biological activities of antimicrobial peptides may be relevant for the innate
      immune response. In particular, ADP-ribosylation of antimicrobial peptides may
      represent a novel escape mechanism adopted by pathogens to facilitate
      colonization of host tissues.

PMID- 22879888
TI  - Bacterial secretion and the role of diffusive and subdiffusive first passage
      processes.
AB  - By funneling protein effectors through needle complexes located on the cellular
      membrane, bacteria are able to infect host cells during type III secretion
      events. The spatio-temporal mechanisms through which these events occur are
      however not fully understood, due in part to the inherent challenges in tracking
      single molecules moving within an intracellular medium. As a result, theoretical
      predictions of secretion times are still lacking. Here we provide a model that
      quantifies, depending on the transport characteristics within bacterial
      cytoplasm, the amount of time for a protein effector to reach either of the
      available needle complexes. Using parameters from Shigella flexneri we are able
      to test the role that translocators might have to activate the needle complexes
      and offer semi-quantitative explanations of recent experimental observations.

PMID- 22879889
TI  - Evolutionary pets: offspring numbers reveal speciation process in domesticated
      chickens.
AB  - Since Darwin, the nature of the relationship between evolution and domestication
      has been debated. Evolution offers different mechanisms of selection that lead to
      adaptation and may end in the origin of new species as defined by the biological
      species concept. Domestication has given rise to numerous breeds in almost every
      domesticated species, including chickens. At the same time, so-called artificial
      selection seems to exclude mechanisms of sexual selection by the animals
      themselves. We want to forward the question to the animal itself: With whom do
      you reproduce successfully? This study focused on the sexual behavior of the
      domestic chicken Gallus gallus f.dom., particularly the White Crested Polish
      breed. Experiments on mate choice and the observation of fertilization and
      hatching rates of mixed-breeding groups revealed breed-specific preferences. In
      breeding groups containing White Crested Polish and a comparative breed, more
      purebred chicks hatched than hybrids (number of eggs collected: 1059). Mating was
      possible in equal shares, but in relation to the number of eggs collected,
      purebred offspring (62.75% +/- 7.10%, M +/- SE) hatched to a greater extend
      compared to hybrid offspring (28.75% +/- 15.32%, M +/- SE). These data
      demonstrate that the mechanism of sexual selection is still present in domestic
      chicken breeds, which includes the alteration of gene frequencies typical for
      domestication and evolutionary speciation. Due to selection and mate choice we
      state that breeding in principle can generate new species. Therefore, we see
      domestication as an evolutionary process that integrates human interests of
      animal breeding with innate mate choice by the animal.

PMID- 22879890
TI  - Prioritizing child health interventions in Ethiopia: modeling impact on child
      mortality, life expectancy and inequality in age at death.
AB  - BACKGROUND: The fourth Millennium Development Goal calls for a two-thirds
      reduction in under-5 mortality between 1990 and 2015. Under-5 mortality rate is
      declining, but many countries are still far from achieving the goal. Effective
      child health interventions that could reduce child mortality exist, but national
      decision-makers lack contextual information for priority setting in their
      respective resource-constrained settings. We estimate the potential health impact
      of increasing coverage of 14 selected health interventions on child mortality in
      Ethiopia (2011-2015). We also explore the impact on life expectancy and
      inequality in the age of death (Gini(health)). METHODS AND FINDINGS: We used the
      Lives Saved Tool to estimate potential impact of scaling-up 14 health
      interventions in Ethiopia (2011-2015). Interventions are scaled-up to 1)
      government target levels, 2) 90% coverage and 3) 90% coverage of the five
      interventions with the highest impact. Under-5 mortality rate, neonatal mortality
      rate and deaths averted are primary outcome measures. We used modified life
      tables to estimate impact on life expectancy at birth and inequality in the age
      of death (Gini(health)). Under-5 mortality rate declines from 101.0 in 2011 to
      68.8, 42.1 and 56.7 per 1000 live births under these three scenarios.
      Prioritizing child health would also increase life expectancy at birth from
      expected 60.5 years in 2015 to 62.5, 64.2 and 63.4 years and reduce inequality in
      age of death (Gini(health)) substantially from 0.24 to 0.21, 0.18 and 0.19.
      CONCLUSIONS: The Millennium Development Goal for child health is reachable in
      Ethiopia. Prioritizing child health would also increase total life expectancy at
      birth and reduce inequality in age of death substantially (Gini(health)).

PMID- 22879891
TI  - Osteopontin reduces biofilm formation in a multi-species model of dental biofilm.
AB  - BACKGROUND: Combating dental biofilm formation is the most effective means for
      the prevention of caries, one of the most widespread human diseases. Among the
      chemical supplements to mechanical tooth cleaning procedures, non-bactericidal
      adjuncts that target the mechanisms of bacterial biofilm formation have gained
      increasing interest in recent years. Milk proteins, such as lactoferrin, have
      been shown to interfere with bacterial colonization of saliva-coated surfaces. We
      here study the effect of bovine milk osteopontin (OPN), a highly phosphorylated
      whey glycoprotein, on a multispecies in vitro model of dental biofilm. While
      considerable research effort focuses on the interaction of OPN with mammalian
      cells, there are no data investigating the influence of OPN on bacterial
      biofilms. METHODOLOGY/PRINCIPAL FINDINGS: Biofilms consisting of Streptococcus
      oralis, Actinomyces naeslundii, Streptococcus mitis, Streptococcus downei and
      Streptococcus sanguinis were grown in a flow cell system that permitted in situ
      microscopic analysis. Crystal violet staining showed significantly less biofilm
      formation in the presence of OPN, as compared to biofilms grown without OPN or
      biofilms grown in the presence of caseinoglycomacropeptide, another
      phosphorylated milk protein. Confocal microscopy revealed that OPN bound to the
      surface of bacterial cells and reduced mechanical stability of the biofilms
      without affecting cell viability. The bacterial composition of the biofilms,
      determined by fluorescence in situ hybridization, changed considerably in the
      presence of OPN. In particular, colonization of S. mitis, the best biofilm former
      in the model, was reduced dramatically. CONCLUSIONS/SIGNIFICANCE: OPN strongly
      reduces the amount of biofilm formed in a well-defined laboratory model of
      acidogenic dental biofilm. If a similar effect can be observed in vivo, OPN might
      serve as a valuable adjunct to mechanical tooth cleaning procedures.

PMID- 22879892
TI  - Polymorphisms in autophagy genes and susceptibility to tuberculosis.
AB  - Recent data suggest that autophagy is important for intracellular killing of
      Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have
      been linked with susceptibility to tuberculosis (TB) among African-Americans, and
      with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22
      polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952
      matched controls, and between patients infected with different M. tuberculosis
      genotypes, as determined by spoligotyping. The same autophagy polymorphisms were
      studied in correlation with ex-vivo production of TNF, IL-1beta, IL-6, IL-8, IFN
      gamma and IL-17 in healthy volunteers. No association was found between TB and
      polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1,
      LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between
      polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the
      successful M. tuberculosis Beijing genotype. The polymorphisms examined were not
      associated with M. tuberculosis induced cytokines, except for a polymorphism in
      ATG10, which was linked with IL-8 production (p = 0.04). All associations found
      lost statistical significance after correction for multiple testing. This first
      examination of a broad set of polymorphisms in autophagy genes fails to show a
      clear association with TB, with M. tuberculosis Beijing genotype infection or
      with ex-vivo pro-inflammatory cytokine production.

PMID- 22879894
TI  - Granulocytes and vascularization regulate uterine bleeding and tissue remodeling
      in a mouse menstruation model.
AB  - Menstruation-associated disorders negatively interfere with the quality of life
      of many women. However, mechanisms underlying pathogenesis of menstrual disorders
      remain poorly investigated up to date. Among others, this is based on a lack of
      appropriate pre-clinical animal models. We here employ a mouse menstruation model
      induced by priming mice with gonadal hormones and application of a physical
      stimulus into the uterus followed by progesterone removal. As in women, these
      events are accompanied by menstrual-like bleeding and tissue remodeling
      processes, i.e. disintegration of decidualized endometrium, as well as subsequent
      repair. We demonstrate that the onset of bleeding coincides with strong
      upregulation of inflammatory mediators and massive granulocyte influx into the
      uterus. Uterine granulocytes play a central role in regulating local tissue
      remodeling since depletion of these cells results in dysregulated expression of
      matrix modifying enzymes. As described here for the first time, uterine blood
      loss can be quantified by help of tampon-like cotton pads. Using this novel
      technique, we reveal that blood loss is strongly reduced upon inhibition of
      endometrial vascularization and thus, is a key regulator of menstrual bleeding.
      Taken together, we here identify angiogenesis and infiltrating granulocytes as
      critical determinants of uterine bleeding and tissue remodeling in a mouse
      menstruation model. Importantly, our study provides a technical and scientific
      basis allowing quantification of uterine blood loss in mice and thus, assessment
      of therapeutic intervention, proving great potential for future use in basic
      research and drug discovery.

PMID- 22879893
TI  - Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.
AB  - INTRODUCTION: Rotavirus vaccine efficacy ranges from >90% in high socio-economic
      settings (SES) to 50% in low SES. With the imminent introduction of rotavirus
      vaccine in low SES countries, understanding reasons for reduced efficacy in these
      settings could identify strategies to improve vaccine performance. METHODS: We
      developed a mathematical model to predict rotavirus vaccine efficacy in high,
      middle and low SES based on data specific for each setting on incidence,
      protection conferred by natural infection and immune response to vaccination. We
      then examined factors affecting efficacy. RESULTS: Vaccination was predicted to
      prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and
      low SES, respectively. Also predicted was that vaccines are most effective
      against severe disease and efficacy declines with age in low but not high SES.
      Reduced immunogenicity of vaccination and reduced protection conferred by natural
      infection are the main factors that compromise efficacy in low SES. DISCUSSION:
      The continued risk of severe disease in non-primary natural infections in low SES
      is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted
      efficacy was remarkably consistent with observed clinical trial results from
      different SES, validating the model. The phenomenon of reduced vaccine efficacy
      can be predicted by intrinsic immunological and epidemiological factors of low
      SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity
      in low SES) and vaccination program (e.g. additional doses) may bring
      improvements.

PMID- 22879895
TI  - N-terminal domain of nuclear IL-1alpha shows structural similarity to the C
      terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.
AB  - Interleukin-1alpha (IL-1alpha) is a proinflammatory cytokine and a key player in
      host immune responses in higher eukaryotes. IL-1alpha has pleiotropic effects on
      a wide range of cell types, and it has been extensively studied for its ability
      to contribute to various autoimmune and inflammation-linked disorders, including
      rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular
      disorders. Interestingly, a significant proportion of IL-1alpha is translocated
      to the cell nucleus, in which it interacts with histone acetyltransferase
      complexes. Despite the importance of IL-1alpha, little is known regarding its
      binding targets and functions in the nucleus. We took advantage of the histone
      acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to
      humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT
      complexes. Using gene knock-out technique and co-immunoprecipitation of the IL
      1alpha precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped
      the IL-1alpha-binding site to the HAT/Core module of the SAGA complex. We also
      predicted the 3-D structure of the IL-1alpha N-terminal domain, and by employing
      structure similarity searches, we found a similar structure in the C-terminal
      regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein
      kinases, which interact with HAT complexes both in mammals and yeast,
      respectively. This finding is further supported with the ability of the IL-1alpha
      precursor to partially rescue growth defects of snf1Delta yeast strains on media
      containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3.
      Finally, the careful evaluation of our data together with other published data in
      the field allows us to hypothesize a new function for the ADA complex in SAGA
      complex assembly.

PMID- 22879896
TI  - Pandemic influenza (A/H1N1) vaccine uptake among French private general
      practitioners: a cross sectional study in 2010.
AB  - BACKGROUND: In July, 2009, French health authorities, like those in many other
      countries, decided to embark on a mass vaccination campaign against the pandemic
      A(H1N1) influenza. Private general practitioners (GPs) were not involved in this
      campaign. We studied GPs' pandemic vaccine (pvaccine) uptake, quantified the
      relative contribution of its potential explanatory factors and studied whether
      their own vaccination choice was correlated with their recommendations to
      patients about pvaccination. METHODOLOGY/PRINCIPAL FINDINGS: In this cross
      sectional telephone survey, professional investigators interviewed an existing
      panel of randomly selected private GPs (N = 1431; response rate at inclusion in
      the panel: 36.8%; participation rate in the survey: 100%). The main outcome
      variable was GPs' own pvaccine uptake. We used an averaging multi-model approach
      to quantify the relative contribution of factors associated with their
      vaccination. The pvaccine uptake rate was 61% (95%CI = 58.3-63.3). Four
      independent factors contributed the most to this rate (partial Nagelkerke's
      R(2)): history of previous vaccination against seasonal influenza (14.5%),
      perception of risks and efficacy of the pvaccine (10.8%), opinions regarding the
      organization of the vaccination campaign (7.1%), and perception of the pandemic's
      severity (5.2%). Overall, 71.3% (95%CI = 69.0-73.6) of the participants
      recommended pvaccination to young adults at risk and 40.1% (95%CI = 37.6-42.7) to
      other young adults. GPs' own pvaccination was strongly predictive of their
      recommendation to both young adults at risk (OR = 9.6; 95%CI = 7.2-12.6) and
      those not at risk (OR = 8.5; 95%CI = 6.4-11.4). CONCLUSIONS/SIGNIFICANCE: These
      results suggest that around 60% of French private GPs followed French
      authorities' recommendations about vaccination of health care professionals
      against the A(H1N1) influenza. They pinpoint priority levers for improving
      preparedness for future influenza pandemics. Besides encouraging GPs' own uptake
      of regular vaccination against seasonal influenza, providing GPs with clear
      information about the risks and efficacy of any new pvaccine and involving them
      in the organization of any future vaccine campaign may improve their pvaccine
      uptake.

PMID- 22879897
TI  - Unusual stability of messenger RNA in snake venom reveals gene expression
      dynamics of venom replenishment.
AB  - Venom is a critical evolutionary innovation enabling venomous snakes to become
      successful limbless predators; it is therefore vital that venomous snakes possess
      a highly efficient venom production and delivery system to maintain their
      predatory arsenal. Here, we exploit the unusual stability of messenger RNA in
      venom to conduct, for the first time, quantitative PCR to characterise the
      dynamics of gene expression of newly synthesised venom proteins following venom
      depletion. Quantitative PCR directly from venom enables real-time dynamic studies
      of gene expression in the same animals because it circumvents the conventional
      requirement to sacrifice snakes to extract mRNA from dissected venom glands.
      Using qPCR and proteomic analysis, we show that gene expression and protein re
      synthesis triggered by venom expulsion peaks between days 3-7 of the cycle of
      venom replenishment, with different protein families expressed in parallel. We
      demonstrate that venom re-synthesis occurs very rapidly following depletion of
      venom stores, presumably to ensure venomous snakes retain their ability to
      efficiently predate and remain defended from predators. The stability of mRNA in
      venom is biologically fascinating, and could significantly empower venom research
      by expanding opportunities to produce transcriptomes from historical venom stocks
      and rare or endangered venomous species, for new therapeutic, diagnostic and
      evolutionary studies.

PMID- 22879898
TI  - Methods to quantify soft-tissue based facial growth and treatment outcomes in
      children: a systematic review.
AB  - CONTEXT: Technological advancements have led craniofacial researchers and
      clinicians into the era of three-dimensional digital imaging for quantitative
      evaluation of craniofacial growth and treatment outcomes. OBJECTIVE: To give an
      overview of soft-tissue based methods for quantitative longitudinal assessment of
      facial dimensions in children until six years of age and to assess the
      reliability of these methods in studies with good methodological quality. DATA
      SOURCE: PubMed, EMBASE, Cochrane Library, Web of Science, Scopus and CINAHL were
      searched. A hand search was performed to check for additional relevant studies.
      STUDY SELECTION: Primary publications on facial growth and treatment outcomes in
      children younger than six years of age were included. DATA EXTRACTION:
      Independent data extraction by two observers. A quality assessment instrument was
      used to determine the methodological quality. Methods, used in studies with good
      methodological quality, were assessed for reliability expressed as the magnitude
      of the measurement error and the correlation coefficient between repeated
      measurements. RESULTS: In total, 47 studies were included describing 4 methods:
      2D x-ray cephalometry; 2D photography; anthropometry; 3D imaging techniques
      (surface laser scanning, stereophotogrammetry and cone beam computed tomography).
      In general the measurement error was below 1 mm and 1 degrees  and correlation
      coefficients range from 0.65 to 1.0. CONCLUSION: Various methods have shown to be
      reliable. However, at present stereophotogrammetry seems to be the best 3D method
      for quantitative longitudinal assessment of facial dimensions in children until
      six years of age due to its millisecond fast image capture, archival
      capabilities, high resolution and no exposure to ionizing radiation.

PMID- 22879899
TI  - Maternal nutritional status predicts adverse birth outcomes among HIV-infected
      rural Ugandan women receiving combination antiretroviral therapy.
AB  - OBJECTIVE: Maternal nutritional status is an important predictor of birth
      outcomes, yet little is known about the nutritional status of HIV-infected
      pregnant women treated with combination antiretroviral therapy (cART). We
      therefore examined the relationship between maternal BMI at study enrollment,
      gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women
      initiating cART in rural Uganda. DESIGN: Prospective cohort. METHODS: HIV
      infected, ART-naive pregnant women were enrolled between 12 and 28 weeks
      gestation and treated with a protease inhibitor or non-nucleoside reverse
      transcriptase inhibitor-based combination regimen. Nutritional status was
      assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were
      evaluated using multivariate analysis. RESULTS: Mean GWG was 0.17 kg/week, 14.6%
      of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse
      fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%),
      fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head
      sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1
      kg/week was associated with LBW, preterm delivery, and a composite adverse
      obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For
      each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%.
      CONCLUSIONS: In our cohort of HIV-infected women initiating cART during
      pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1
      kg/week were at increased risk for LBW, preterm delivery, and composite adverse
      birth outcomes. cART by itself may not be sufficient for decreasing the burden of
      adverse birth outcomes among HIV-infected women. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00993031.

PMID- 22879900
TI  - Communities of arbuscular mycorrhizal fungi detected in forest soil are spatially
      heterogeneous but do not vary throughout the growing season.
AB  - Despite the important ecosystem role played by arbuscular mycorrhizal fungi
      (AMF), little is known about spatial and temporal variation in soil AMF
      communities. We used pyrosequencing to characterise AMF communities in soil
      samples (n = 44) from a natural forest ecosystem. Fungal taxa were identified by
      BLAST matching of reads against the MaarjAM database of AMF SSU rRNA gene
      diversity. Sub-sampling within our dataset and experimental shortening of a set
      of long reads indicated that our approaches to taxonomic identification and
      diversity analysis were robust to variations in pyrosequencing read length and
      numbers of reads per sample. Different forest plots (each 10 * 10 m and separated
      from one another by 30 m) contained significantly different soil AMF communities,
      and the pairwise similarity of communities decreased with distance up to 50 m.
      However, there were no significant changes in community composition between
      different time points in the growing season (May-September). Spatial structure in
      soil AMF communities may be related to the heterogeneous vegetation of the
      natural forest study system, while the temporal stability of communities suggests
      that AMF in soil represent a fairly constant local species pool from which
      mycorrhizae form and disband during the season.

PMID- 22879901
TI  - Scavenger receptors in human airway epithelial cells: role in response to double
      stranded RNA.
AB  - Scavenger receptors and Toll-like receptors (TLRs) cooperate in response to
      danger signals to adjust the host immune response. The TLR3 agonist double
      stranded (ds)RNA is an efficient activator of innate signalling in bronchial
      epithelial cells. In this study, we aimed at defining the role played by
      scavenger receptors expressed by bronchial epithelial cells in the control of the
      innate response to dsRNA both in vitro and in vivo. Expression of several
      scavenger receptor involved in pathogen recognition was first evaluated in human
      bronchial epithelial cells in steady-state and inflammatory conditions. Their
      implication in the uptake of dsRNA and the subsequent cell activation was
      evaluated in vitro by competition with ligand of scavenger receptors including
      maleylated ovalbumin and by RNA silencing. The capacity of maleylated ovalbumin
      to modulate lung inflammation induced by dsRNA was also investigated in mice.
      Exposure to tumor necrosis factor-alpha increased expression of the scavenger
      receptors LOX-1 and CXCL16 and the capacity to internalize maleylated ovalbumin,
      whereas activation by TLR ligands did not. In contrast, the expression of SR-B1
      was not modulated in these conditions. Interestingly, supplementation with
      maleylated ovalbumin limited dsRNA uptake and inhibited subsequent activation of
      bronchial epithelial cells. RNA silencing of LOX-1 and SR-B1 strongly blocked the
      dsRNA-induced cytokine production. Finally, administration of maleylated
      ovalbumin in mice inhibited the dsRNA-induced infiltration and activation of
      inflammatory cells in bronchoalveolar spaces and lung draining lymph nodes.
      Together, our data characterize the function of SR-B1 and LOX-1 in bronchial
      epithelial cells and their implication in dsRNA-induced responses, a finding that
      might be relevant during respiratory viral infections.

PMID- 22879902
TI  - Vagaries of fluorochrome reporter gene expression in Foxp3+ regulatory T cells.
AB  - CD4(+)CD25(+) regulatory T (Treg) cell lineage commitment and expression of the
      transcription factor Foxp3 can be induced at the CD4(+)CD8(+) double-positive
      (DP) and CD4(+)CD8(?) single-positive stages of thymic development, as well as in
      postthymic CD4(+) T cells in peripheral lymphoid tissues. The availability of
      transgenic mice with Foxp3-dependent fluorochrome reporter gene expression has
      greatly facilitated studies on the intra- and extrathymic generation of murine
      Foxp3(+) Treg cells. Here, we performed a comparative analysis of thymic Treg
      cell development and peripheral compartments of mature Treg cells in various
      transgenic strains with gene targeted and bacterial artificial chromosome (BAC)
      driven Foxp3-fluorochrome expression. These studies revealed a relative
      deficiency of Foxp3(+) DP thymocytes selectively in mice with targeted insertion
      of the fluorochrome reporter gene coding sequence into the endogenous Foxp3 gene.
      While Foxp3 BAC-driven fluorochrome expression in ex vivo CD4(+) T cells was
      found to faithfully reflect Foxp3 protein expression, we provide evidence that
      Foxp3 BAC transgenesis can result in sizable populations of Foxp3(+) Treg cells
      that lack fluorochrome reporter expression. This could be attributed to both
      timely delayed up-regulation of BAC expression in developing Treg cells and the
      accumulation of peripheral Foxp3(+) Treg cells with continuous transcriptional
      inactivity of the Foxp3 BAC transgene.

PMID- 22879903
TI  - PATHLOGIC-S: a scalable Boolean framework for modelling cellular signalling.
AB  - Curated databases of signal transduction have grown to describe several thousand
      reactions, and efficient use of these data requires the development of modelling
      tools to elucidate and explore system properties. We present PATHLOGIC-S, a
      Boolean specification for a signalling model, with its associated GPL-licensed
      implementation using integer programming techniques. The PATHLOGIC-S
      specification has been designed to function on current desktop workstations, and
      is capable of providing analyses on some of the largest currently available
      datasets through use of Boolean modelling techniques to generate predictions of
      stable and semi-stable network states from data in community file formats.
      PATHLOGIC-S also addresses major problems associated with the presence and
      modelling of inhibition in Boolean systems, and reduces logical incoherence due
      to common inhibitory mechanisms in signalling systems. We apply this approach to
      signal transduction networks including Reactome and two pathways from the Panther
      Pathways database, and present the results of computations on each along with a
      discussion of execution time. A software implementation of the framework and
      model is freely available under a GPL license.

PMID- 22879904
TI  - Inhaled carbon monoxide provides cerebral cytoprotection in pigs.
AB  - Carbon monoxide (CO) at low concentrations imparts protective effects in numerous
      preclinical small animal models of brain injury. Evidence of protection in large
      animal models of cerebral injury, however, has not been tested. Neurologic
      deficits following open heart surgery are likely related in part to ischemia
      reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a
      model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the
      effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB)
      induced significant alterations in metabolic demands, including a decrease in the
      oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise
      in cerebral blood pressure that ultimately resulted in increased cell death in
      the neocortex and hippocampus that was completely abrogated in piglets
      preconditioned with a low, safe dose of CO. Moreover CO-treated animals
      maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures
      with no change in systemic hemodynamics or metabolic intermediates. Collectively,
      our data demonstrate that inhaled CO may be beneficial in preventing cerebral
      injury resulting from DHCA and offer important therapeutic options in newborns
      undergoing DHCA for open heart surgery.

PMID- 22879905
TI  - Complete mitochondrial genome of the free-living earwig, Challia fletcheri
      (Dermaptera: Pygidicranidae) and phylogeny of Polyneoptera.
AB  - The insect order Dermaptera, belonging to Polyneoptera, includes ~2,000 extant
      species, but no dermapteran mitochondrial genome has been sequenced. We sequenced
      the complete mitochondrial genome of the free-living earwig, Challia fletcheri,
      compared its genomic features to other available mitochondrial sequences from
      polyneopterous insects. In addition, the Dermaptera, together with the other
      known polyneopteran mitochondrial genome sequences (protein coding, ribosomal
      RNA, and transfer RNA genes), were employed to understand the phylogeny of
      Polyneoptera, one of the least resolved insect phylogenies, with emphasis on the
      placement of Dermaptera. The complete mitochondrial genome of C. fletcheri
      presents the following several unusual features: the longest size in insects is
      20,456 bp; it harbors the largest tandem repeat units (TRU) among insects; it
      displays T- and G-skewness on the major strand and A- and C-skewness on the minor
      strand, which is a reversal of the general pattern found in most insect
      mitochondrial genomes, and it possesses a unique gene arrangement characterized
      by a series of gene translocations and/or inversions. The reversal pattern of
      skewness is explained in terms of inversion of replication origin. All
      phylogenetic analyses consistently placed Dermaptera as the sister to Plecoptera,
      leaving them as the most basal lineage of Polyneoptera or sister to
      Ephemeroptera, and placed Odonata consistently as the most basal lineage of the
      Pterygota.

PMID- 22879906
TI  - Aging of the microenvironment influences clonality in hematopoiesis.
AB  - The mechanisms of the age-associated exponential increase in the incidence of
      leukemia are not known in detail. Leukemia as well as aging are initiated and
      regulated in multi-factorial fashion by cell-intrinsic and extrinsic factors. The
      role of aging of the microenvironment for leukemia initiation/progression has not
      been investigated in great detail so far. Clonality in hematopoiesis is tightly
      linked to the initiation of leukemia. Based on a retroviral-insertion mutagenesis
      approach to generate primitive hematopoietic cells with an intrinsic potential
      for clonal expansion, we determined clonality of transduced hematopoietic
      progenitor cells (HPCs) exposed to a young or aged microenvironment in vivo.
      While HPCs displayed primarily oligo-clonality within a young microenvironment,
      aged animals transplanted with identical pool of cells displayed reduced
      clonality within transduced HPCs. Our data show that an aged niche exerts a
      distinct selection pressure on dominant HPC-clones thus facilitating the
      transition to mono-clonality, which might be one underlying cause for the
      increased age-associated incidence of leukemia.

PMID- 22879907
TI  - SNP discovery using Next Generation Transcriptomic Sequencing in Atlantic herring
      (Clupea harengus).
AB  - The introduction of Next Generation Sequencing (NGS) has revolutionised
      population genetics, providing studies of non-model species with unprecedented
      genomic coverage, allowing evolutionary biologists to address questions
      previously far beyond the reach of available resources. Furthermore, the simple
      mutation model of Single Nucleotide Polymorphisms (SNPs) permits cost-effective
      high-throughput genotyping in thousands of individuals simultaneously. Genomic
      resources are scarce for the Atlantic herring (Clupea harengus), a small pelagic
      species that sustains high revenue fisheries. This paper details the development
      of 578 SNPs using a combined NGS and high-throughput genotyping approach. Eight
      individuals covering the species distribution in the eastern Atlantic were bar
      coded and multiplexed into a single cDNA library and sequenced using the 454 GS
      FLX platform. SNP discovery was performed by de novo sequence clustering and
      contig assembly, followed by the mapping of reads against consensus contig
      sequences. Selection of candidate SNPs for genotyping was conducted using an in
      silico approach. SNP validation and genotyping were performed simultaneously
      using an Illumina 1,536 GoldenGate assay. Although the conversion rate of
      candidate SNPs in the genotyping assay cannot be predicted in advance, this
      approach has the potential to maximise cost and time efficiencies by avoiding
      expensive and time-consuming laboratory stages of SNP validation. Additionally,
      the in silico approach leads to lower ascertainment bias in the resulting SNP
      panel as marker selection is based only on the ability to design primers and the
      predicted presence of intron-exon boundaries. Consequently SNPs with a wider
      spectrum of minor allele frequencies (MAFs) will be genotyped in the final panel.
      The genomic resources presented here represent a valuable multi-purpose resource
      for developing informative marker panels for population discrimination,
      microarray development and for population genomic studies in the wild.

PMID- 22879908
TI  - Effects of pregabalin on central sensitization in patients with chronic
      pancreatitis in a randomized, controlled trial.
AB  - BACKGROUND: Intense abdominal pain is the dominant feature of chronic
      pancreatitis. During the disease changes in central pain processing, e.g. central
      sensitization manifest as spreading hyperalgesia, can result from ongoing
      nociceptive input. The aim of the present study is to evaluate the effect of
      pregabalin on pain processing in chronic pancreatitis as assessed by quantitative
      sensory testing (QST). METHODS: This randomized, double-blind, placebo-controlled
      trial evaluated effects of pregabalin on pain processing. QST was used to
      quantify pain processing by measuring thresholds to painful electrical and
      pressure stimulation in six body dermatomes. Descending endogenous pain
      modulation was quantified using the conditioned pain modulation (CPM) paradigm to
      elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect
      parameter was the change in the sum of all body pain threshold values after three
      weeks of study treatment versus baseline values between both treatment groups.
      RESULTS: 64 patients were analyzed. No differences in change in sum of pain
      thresholds were present for pregabalin vs. placebo after three weeks of
      treatment. For individual dermatomes, change vs. baseline pain thresholds was
      significantly greater in pregabalin vs. placebo patients for electric pain
      detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P
      = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P =
      0.004). No differences were observed between pregabalin and placebo regarding
      conditioned pain modulation. CONCLUSION: Our study provides first evidence that
      pregabalin has moderate inhibitory effects on central sensitization manifest as
      spreading hyperalgesia in chronic pancreatitis patients. These findings suggest
      that QST can be of clinical use for monitoring pain treatments in the context of
      chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT00755573.

PMID- 22879909
TI  - Tagging single nucleotide polymorphisms in the IRF1 and IRF8 genes and
      tuberculosis susceptibility.
AB  - Genes encoding IRF1 and IRF8 protein have been proposed as candidate tuberculosis
      susceptibility genes. In order to elucidate whether the IRF1 and IRF8 variants
      were associated with tuberculosis susceptibility, we conducted a case-control
      study consisting of 495 controls and 452 ethnically matched cases with
      tuberculosis in a Chinese population. Seven haplotype tagging single-nucleotide
      polymorphisms (tagSNPs) (rs2057656; rs2706381; rs2070724; rs2070721; rs2549008;
      rs2549007; rs2706386) from HapMap database were analyzed, which provided an
      almost complete coverage of the genetic variations in the IRF1 gene. Fifteen
      tagSNPs (rs12924316; rs182511; rs305080; rs2292980; rs925994; rs424971;
      rs16939967; rs11117415; rs4843860; rs9926411; rs8064189; rs12929551; rs10514611;
      rs1044873; rs6638) were observed in the IRF8 gene. All these tagSNPs were
      genotyped by SNPstream genotyping and SNaPshot typing. None of the seven tagSNPs
      was individually associated with tuberculosis in the IRF1 gene. In the IRF8 gene,
      interestingly, we found that three tagSNPs (rs925994 and rs11117415 located in
      the intron region; rs10514611 located in the 3'UTR) were associated with risk of
      tuberculosis after Bonferroni correction. Per allele OR was 1.75 (95% CI 1.35 ~
      2.27, P = 0.002), 4.75 (95% CI 2.16 ~ 10.43, P = 0.002) and 3.39 (95% CI 1.60 ~
      7.20, P = 0.015) respectively. Luciferase reporter gene assay showed that the
      construct that contained the non-risk allele C of rs10514611 showed significantly
      higher luciferase activity than did the risk T allele (P<0.01), which implied
      rs10514611 was a potential functional SNP site. Our results indicated that the
      IRF8 gene might participate in genetic susceptibility to tuberculosis in a
      Chinese population.

PMID- 22879910
TI  - Binding of the heterogeneous ribonucleoprotein K (hnRNP K) to the Epstein-Barr
      virus nuclear antigen 2 (EBNA2) enhances viral LMP2A expression.
AB  - The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the
      in vitro transformation of B-lymphocytes, interferes with cellular processes by
      binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG)
      repeat element contains either symmetrically or asymmetrically di-methylated
      arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA
      modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA
      RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2)
      Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an
      epitope shared with cellular proteins that is used for interaction with target
      structures. With monoclonal antibodies against the modified RG-repeat, we indeed
      identified cellular homologues that apparently have the same surface structure as
      methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm
      protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to
      SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous
      ribonucleoprotein K (hnRNP K). Specific binding of the ADMA- antibody to hnRNP K
      was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we
      show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally,
      hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane
      protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a
      direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our
      data support the notion that the methylated surface of EBNA2 mimics the surface
      structure of cellular proteins to interfere with or co-opt their functional
      properties.

PMID- 22879912
TI  - Quantitative model of cell cycle arrest and cellular senescence in primary human
      fibroblasts.
AB  - Primary human fibroblasts in tissue culture undergo a limited number of cell
      divisions before entering a non-replicative "senescent" state. At early
      population doublings (PD), fibroblasts are proliferation-competent displaying
      exponential growth. During further cell passaging, an increasing number of cells
      become cell cycle arrested and finally senescent. This transition from
      proliferating to senescent cells is driven by a number of endogenous and
      exogenous stress factors. Here, we have developed a new quantitative model for
      the stepwise transition from proliferating human fibroblasts (P) via reversibly
      cell cycle arrested (C) to irreversibly arrested senescent cells (S). In this
      model, the transition from P to C and to S is driven by a stress function gamma
      and a cellular stress response function F which describes the time-delayed
      cellular response to experimentally induced irradiation stress. The application
      of this model based on senescence marker quantification at the single-cell level
      allowed to discriminate between the cellular states P, C, and S and delivers the
      transition rates between the P, C and S states for different human fibroblast
      cell types. Model-derived quantification unexpectedly revealed significant
      differences in the stress response of different fibroblast cell lines. Evaluating
      marker specificity, we found that SA-beta-Gal is a good quantitative marker for
      cellular senescence in WI-38 and BJ cells, however much less so in MRC-5 cells.
      Furthermore we found that WI-38 cells are more sensitive to stress than BJ and
      MRC-5 cells. Thus, the explicit separation of stress induction from the cellular
      stress response, and the differentiation between three cellular states P, C and S
      allows for the first time to quantitatively assess the response of primary human
      fibroblasts towards endogenous and exogenous stress during cellular ageing.

PMID- 22879911
TI  - Detection of IGF2BP3, HOXB7, and NEK2 mRNA expression in brush cytology specimens
      as a new diagnostic tool in patients with biliary strictures.
AB  - INTRODUCTION: It is a challenging task to distinguish between benign and
      malignant lesions in patients with biliary strictures. Here we analyze whether
      determination of target gene mRNA levels in intraductal brush cytology specimens
      may be used to improve the diagnosis of bile duct carcinoma. MATERIALS AND
      METHODS: Brush cytology specimens from 119 patients with biliary strictures
      (malignant: n = 72; benign: n = 47) were analyzed in a retrospective cohort
      study. mRNA of IGF-II mRNA-binding protein 3 (IGF2BP3), homeobox B7 (HOXB7),
      Forkhead box M1 (FOXM1), kinesin family member 2C (KIF2C) and serine/threonine
      kinase NEK2 was determined by semi-quantitative RT-PCR using the DeltaCt method.
      RESULTS: IGF2BP3 (p<0.0001), HOXB7 (p<0.0001), and NEK2 (p<0.0001) mRNA
      expression levels were significantly increased in patients with
      cholangiocarcinoma or pancreatic cancer. Median DeltaCt values differed by 3.5
      cycles (IGF2BP3), 2.8 cycles (HOXB7) and 1.3 cycles (NEK2) corresponding to 11
      fold, 7-fold and 2.5-fold increased mRNA levels in malignant versus benign
      samples. Sensitivity to detect biliary cancer was 76.4% for IGF2BP3 (80.9%
      specificity); 72.2% for HOXB7 (78.7% specificity) and 65.3% for NEK2 (72.3%
      specificity), whereas routine cytology reached only 43.1% sensitivity (85.4%
      specificity). Diagnostic precision was further improved, when all three molecular
      markers were assessed in combination (77.8% sensitivity, 87.2% specificity) and
      achieved 87.5% sensitivity and 87.2% specificity when molecular markers were
      combined with routine cytology. CONCLUSIONS: Our data suggest that measuring
      IGF2BP3, HOXB7 and NEK2 mRNA levels by RT-PCR in addition to cytology has the
      potential to improve detection of malignant biliary disorders from brush cytology
      specimens.

PMID- 22879913
TI  - AP-1 mediated transcriptional repression of matrix metalloproteinase-9 by
      recruitment of histone deacetylase 1 in response to interferon beta.
AB  - Matrix metalloproteinase-9 (MMP-9) is a 92 kDa zinc-dependant endopeptidase that
      degrades components of the extracellular matrix. Increased expression of MMP-9 is
      implicated in many pathological conditions including metastatic cancer, multiple
      sclerosis, and atherosclerosis. Although it has been widely noted that interferon
      beta (IFNbeta) downregulates both the basal and phorbol 12-myristate 13-acetate
      (PMA)-induced MMP-9 expression at the transcriptional level, the molecular
      mechanism of this repression is poorly understood. In the present study we
      identify a novel mechanism for repression of MMP-9 transcription by IFNbeta in
      HT1080 fibrosarcoma cells. Using reporter assays with promoter deletion
      constructs we show that IFNbeta's inhibitory effects require a region of the
      promoter between -154 and -72, which contains an AP-1 binding site. Chromatin
      immunoprecipitation (ChIP) studies indicate that IFNbeta increases histone
      deacetylase (HDAC)-1 recruitment to the MMP-9 promoter and reduces histone H3
      acetylation, in addition to reduced NF-kappaB recruitment. ChIP analysis shows
      that IFNbeta induced HDAC1 recruitment to the MMP-9 promoter and IFNbeta mediated
      transcriptional repression is lost when the AP-1 binding site is inactivated by a
      point mutation. Altogether, our results establish that the repression of MMP-9
      transcription in response to IFNbeta occurs by the recruitment of HDAC1 via the
      proximal AP-1 binding site.

PMID- 22879914
TI  - COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model
      for chronic hepatitis and fibrosis.
AB  - New therapeutic concepts developed in rodent models should ideally be evaluated
      in large animal models prior to human clinical application. COMMD1-deficiency in
      dogs leads to hepatic copper accumulation and chronic hepatitis representing a
      Wilson's disease like phenotype. Detailed understanding of the pathogenesis and
      time course of this animal model is required to test its feasibility as a large
      animal model for chronic hepatitis. In addition to mouse models, true
      longitudinal studies are possible due to the size of these dogs permitting
      detailed analysis of the sequence of events from initial insult to final
      cirrhosis. Therefore, liver biopsies were taken each half year from five new born
      COMMD1-deficient dogs over a period of 42 months. Biopsies were used for H&E,
      reticulin, and rubeanic acid (copper) staining. Immunohistochemistry was
      performed on hepatic stellate cell (HSC) activation marker (alpha-smooth muscle
      actin, alpha-SMA), proliferation (Ki67), apoptosis (caspase-3), and bile duct and
      liver progenitor cell (LPC) markers keratin (K) 19 and 7. Quantitative RT-PCR and
      Western Blots were performed on gene products involved in the regenerative and
      fibrotic pathways. Maximum copper accumulation was reached at 12 months of age,
      which coincided with the first signs of hepatitis. HSCs were activated (alpha
      SMA) from 18 months onwards, with increasing reticulin deposition and hepatocytic
      proliferation in later stages. Hepatitis and caspase-3 activity (first noticed at
      18 months) increased over time. Both HGF and TGF-beta1 gene expression peaked at
      24 months, and thereafter decreased gradually. Both STAT3 and c-MET showed an
      increased time-dependent activation. Smad2/3 phosphorylation, indicative for
      fibrogenesis, was present at all time-points. COMMD1-deficient dogs develop
      chronic liver disease and cirrhosis comparable to human chronic hepatitis,
      although at much higher pace. Therefore they represent a genetically-defined
      large animal model to test clinical applicability of new therapeutics developed
      in rodent models.

PMID- 22879915
TI  - beta-Cell regeneration mediated by human bone marrow mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes
      in animal models. The mechanism, however, remains largely unknown. An unanswered
      question is whether BMSCs are able to differentiate into beta-cells in vivo, or
      whether BMSCs are able to mediate recovery and/or regeneration of endogenous beta
      cells. Here we examined these questions by testing the ability of hBMSCs
      genetically modified to transiently express vascular endothelial growth factor
      (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether
      these cells were differentiated into beta-cells or mediated recovery through
      alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed
      hyperglycemia in more than half of the diabetic mice and induced overall improved
      survival and weight maintenance in all mice. Recovery was sustained only in the
      mice treated with hBMSCs-VEGF. However, de novo beta-cell differentiation from
      human cells was observed in mice in both cases, treated with either hBMSCs-VEGF
      or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained
      reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous beta
      cell regeneration and correlated with activation of the insulin/IGF receptor
      signaling pathway involved in maintaining beta-cell mass and function. Our study
      demonstrated the possible benefit of hBMSCs for the treatment of insulin
      dependent diabetes and gives new insight into the mechanism of beta-cell recovery
      after injury mediated by hBMSC therapy.

PMID- 22879916
TI  - Host longevity and parasite species richness in mammals.
AB  - Hosts and parasites co-evolve, with each lineage exerting selective pressures on
      the other. Thus, parasites may influence host life-history characteristics, such
      as longevity, and simultaneously host life-history may influence parasite
      diversity. If parasite burden causes increased mortality, we expect a negative
      association between host longevity and parasite species richness. Alternatively,
      if long-lived species represent a more stable environment for parasite
      establishment, host longevity and parasite species richness may show a positive
      association. We tested these two opposing predictions in carnivores, primates and
      terrestrial ungulates using phylogenetic comparative methods and controlling for
      the potentially confounding effects of sampling effort and body mass. We also
      tested whether increased host longevity is associated with increased immunity,
      using white blood cell counts as a proxy for immune investment. Our analyses
      revealed weak relationships between parasite species richness and longevity. We
      found a significant negative relationship between longevity and parasite species
      richness for ungulates, but no significant associations in carnivores or
      primates. We also found no evidence for a relationship between immune investment
      and host longevity in any of our three groups. Our results suggest that greater
      parasite burden is linked to higher host mortality in ungulates. Thus, shorter
      lived ungulates may be more vulnerable to disease outbreaks, which has
      implications for ungulate conservation, and may be applicable to other short
      lived mammals.

PMID- 22879917
TI  - Sleep improves memory: the effect of sleep on long term memory in early
      adolescence.
AB  - Sleep plays an important role in the consolidation of memory. This has been most
      clearly shown in adults for procedural memory (i.e. skills and procedures) and
      declarative memory (e.g. recall of facts). The effects of sleep and memory are
      relatively unstudied in adolescents. Declarative memory is important in school
      performance and consequent social functioning in adolescents. This is the first
      study to specifically examine the effects of normal sleep on auditory declarative
      memory in an early adolescent sample. Given that the majority of adolescents do
      not obtain the recommended amount of sleep, it is critical to study the cognitive
      effects of normal sleep. Forty male and female normal, healthy adolescents
      between the ages of ten and fourteen years old were randomly assigned to sleep
      and no sleep conditions. Subjects were trained on a paired-associate declarative
      memory task and a control working memory task at 9 am, and tested at night (12
      hours later) without sleep. The same number of subjects was trained at 9 pm and
      tested 9 am following sleep. An increase of 20.6% in declarative memory, as
      measured by the number correct in a paired-associate test, following sleep was
      observed compared to the group which was tested at the same time interval without
      sleep (p<0.03). The performance on the control working memory task that involved
      encoding and memoranda manipulation was not affected by time of day or
      relationship to sleep. Declarative memory is significantly improved by sleep in a
      sample of normal adolescents.

PMID- 22879918
TI  - Expression, purification, and mass spectrometric analysis of 15N, 13C-labeled RGD
      hirudin, expressed in Pichia pastoris, for NMR studies.
AB  - A novel recombinant hirudin, RGD-hirudin, inhibits the activity of thrombin and
      the aggregation of platelets. Here, we successfully expressed (15)N, (13)C
      labeled RGD-hirudin in Pichia pastoris in a fermenter. The protein was
      subsequently purified to yield sufficient quantities for structural and
      functional studies. The purified protein was characterized by HPLC and MALDI-TOF
      mass spectroscopy. Analysis revealed that the protein was pure and uniformly
      labeled with (15)N and (13)C. A bioassay showed that the anti-thrombin activity
      and the anti-platelet aggregation ability of the labeled protein were the same as
      those of unlabeled RGD-hirudin. Multidimensional heteronuclear NMR spectroscopy
      has been used to determine almost complete backbone (15)N, (13)C and (1)H
      resonance assignments of the r-RGD-Hirudin. The (15)N-(1)H HSQC spectrum of
      uniformly (15)N, (13)C-labeled RGD-hirudin allowed successful assignment of the
      signals. Examples of the quality of the data are provided for the (15)N-(l)H
      correlation spectrum, and by selected planes of the CBCA(CO)NH, CBCANH, and HNCO
      experiments. These results provide a basis for further studies on the structure
      function relationship of RGD-hirudin with thrombin and platelets.

PMID- 22879919
TI  - A low-cost microfluidic chip for rapid genotyping of malaria-transmitting
      mosquitoes.
AB  - BACKGROUND: Vector control is one of the most effective measures to prevent the
      transmission of malaria, a disease that causes over 600,000 deaths annually.
      Around 30-40 Anopheles mosquito species are natural vectors of malaria parasites.
      Some of these species cannot be morphologically distinguished, but have
      behavioral and ecological differences. Emblematic of this is the Anopheles
      gambiae species complex. The correct identification of vector species is
      fundamental to the development of control strategies and epidemiological studies
      of disease transmission. METHODOLOGY/PRINCIPAL FINDINGS: An inexpensive,
      disposable, field-deployable, sample-to-answer, microfluidic chip was designed,
      constructed, and tested for rapid molecular identification of Anopheles gambiae
      and Anopheles arabiensis. The chip contains three isothermal amplification
      reactors. One test reactor operates with specific primers to amplify Anopheles
      gambiae DNA, another with specific primers for Anopheles arabiensis DNA, and the
      third serves as a negative control. A mosquito leg was crushed on an isolation
      membrane. Two discs, laden with mosquito tissue, were punched out of the membrane
      and inserted into the two test chambers. The isolated, disc-bound DNA served as a
      template in the amplification processes. The amplification products were detected
      with intercalating fluorescent dye that was excited with a blue light-emitting
      diode. The emitted light was observed by eye and recorded with a cell-phone
      camera. When the target consisted of Anopheles gambiae, the reactor containing
      primers specific to An. gambiae lit up while the other two reactors remained
      dark. When the target consisted of Anopheles arabiensis, the reactor containing
      primers specific to An. arabiensis lit up while the other two reactors remained
      dark. CONCLUSIONS/SIGNIFICANCE: The microfluidic chip provides a means to
      identify mosquito type through molecular analysis. It is suitable for field work,
      allowing one to track the geographical distribution of mosquito populations and
      community structure alterations due to environmental changes and malaria
      intervention measures.

PMID- 22879920
TI  - Role of the Irr protein in the regulation of iron metabolism in Rhodobacter
      sphaeroides.
AB  - In Rhizobia the Irr protein is an important regulator for iron-dependent gene
      expression. We studied the role of the Irr homolog RSP_3179 in the photosynthetic
      alpha-proteobacterium Rhodobacter sphaeroides. While Irr had little effect on
      growth under iron-limiting or non-limiting conditions its deletion resulted in
      increased resistance to hydrogen peroxide and singlet oxygen. This correlates
      with an elevated expression of katE for catalase in the Irr mutant compared to
      the wild type under non-stress conditions. Transcriptome studies revealed that
      Irr affects the expression of genes for iron metabolism, but also has some
      influence on genes involved in stress response, citric acid cycle, oxidative
      phosphorylation, transport, and photosynthesis. Most genes showed higher
      expression levels in the wild type than in the mutant under normal growth
      conditions indicating an activator function of Irr. Irr was however not required
      to activate genes of the iron metabolism in response to iron limitation, which
      showed even stronger induction in the absence of Irr. This was also true for
      genes mbfA and ccpA, which were verified as direct targets for Irr. Our results
      suggest that in R. sphaeroides Irr diminishes the strong induction of genes for
      iron metabolism under iron starvation.

PMID- 22879921
TI  - Multi-reception strategy with improved SNR for multichannel MR imaging.
AB  - A multi-reception strategy with extended GRAPPA is proposed in this work to
      improve MR imaging performance at ultra-high field MR systems with limited
      receiver channels. In this method, coil elements are separated to two or more
      groups under appropriate grouping criteria. Those groups are enabled in sequence
      for imaging first, and then parallel acquisition is performed to compensate for
      the redundant scan time caused by the multiple receptions. To efficiently
      reconstruct the data acquired from elements of each group, a specific extended
      GRAPPA was developed. This approach was evaluated by using a 16-element head
      array on a 7 Tesla whole-body MRI scanner with 8 receive channels. The in-vivo
      experiments demonstrate that with the same scan time, the 16-element array with
      twice receptions and acceleration rate of 2 can achieve significant SNR gain in
      the periphery area of the brain and keep nearly the same SNR in the center area
      over an eight-element array, which indicates the proposed multi-reception
      strategy and extended GRAPPA are feasible to improve image quality for MRI
      systems with limited receive channels. This study also suggests that it is
      advantageous for a MR system with N receiver channels to utilize a coil array
      with more than N elements if an appropriate acquisition strategy is applied.

PMID- 22879922
TI  - Rare primary mitochondrial DNA mutations and probable synergistic variants in
      Leber's hereditary optic neuropathy.
AB  - BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited
      blinding disorder, which in over 90% of cases is due to one of three primary
      mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C,
      respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA
      mutations causing the remaining 10% of cases is only partially and often poorly
      defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to improve such a list of
      pathological variants, we completely sequenced the mitochondrial genomes of
      suspected LHON patients from Italy, France and Germany, lacking the three primary
      common mutations. Phylogenetic and conservation analyses were performed. Sixteen
      mitochondrial genomes were found to harbor at least one of the following nine
      rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A
      C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6
      (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S).
      Phylogenetic analyses revealed that these substitutions were due to independent
      events on different haplogroups, whereas interspecies comparisons showed that
      they affected conserved amino acid residues or domains in the ND subunit genes of
      complex I. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that these nine
      substitutions are all primary LHON mutations. Therefore, despite their relative
      low frequency, they should be routinely tested for in all LHON patients lacking
      the three common mutations. Moreover, our sequence analysis confirms the major
      role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the
      general population of Western Europe) and other putative synergistic mtDNA
      variants in LHON expression.

PMID- 22879923
TI  - Storage-induced changes in erythrocyte membrane proteins promote recognition by
      autoantibodies.
AB  - Physiological erythrocyte removal is associated with a selective increase in
      expression of neoantigens on erythrocytes and their vesicles, and subsequent
      autologous antibody binding and phagocytosis. Chronic erythrocyte transfusion
      often leads to immunization and the formation of alloantibodies and
      autoantibodies. We investigated whether erythrocyte storage leads to the
      increased expression of non-physiological antigens. Immunoprecipitations were
      performed with erythrocytes and vesicles from blood bank erythrocyte concentrates
      of increasing storage periods, using patient plasma containing erythrocyte
      autoantibodies. Immunoprecipitate composition was identified using proteomics.
      Patient plasma antibody binding increased with erythrocyte storage time, while
      the opposite was observed for healthy volunteer plasma, showing that pathology
      associated antigenicity changes during erythrocyte storage. Several membrane
      proteins were identified as candidate antigens. The protein complexes that were
      precipitated by the patient antibodies in erythrocytes were different from the
      ones in the vesicles formed during erythrocyte storage, indicating that the
      storage-associated vesicles have a different immunization potential. Soluble
      immune mediators including complement factors were present in the patient plasma
      immunoprecipitates, but not in the allogeneic control immunoprecipitates. The
      results support the theory that disturbed erythrocyte aging during storage of
      erythrocyte concentrates contributes to transfusion-induced alloantibody and
      autoantibody formation.

PMID- 22879924
TI  - Risk of hormone escape in a human prostate cancer model depends on therapy
      modalities and can be reduced by tyrosine kinase inhibitors.
AB  - Almost all prostate cancers respond to androgen deprivation treatment but many
      recur. We postulated that risk of hormone escape--frequency and delay--are
      influenced by hormone therapy modalities. More, hormone therapies induce crucial
      biological changes involving androgen receptors; some might be targets for escape
      prevention. We investigated the relationship between the androgen deprivation
      treatment and the risk of recurrence using nude mice bearing the high grade,
      hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were
      treated by Luteinizing-Hormone Releasing Hormone (LHRH) antagonist alone,
      continuous or intermittent regimen, or combined with androgen receptor (AR)
      antagonists (bicalutamide or flutamide). Tumor growth was monitored. Biological
      changes were studied as for genomic alterations, AR mutations and protein
      expression in a large series of recurrent tumors according to hormone therapy
      modalities. Therapies targeting Her-2 or AKT were tested in combination with
      castration. All statistical tests were two-sided. Tumor growth was inhibited by
      continuous administration of the LH-RH antagonist degarelix (castration), but 40%
      of tumors recurred. Intermittent castration or complete blockade induced by
      degarelix and antiandrogens combination, inhibited tumor growth but increased the
      risk of recurrence (RR) as compared to continuous castration (RR(intermittent):
      14.5, RR(complete blockade): 6.5 and 1.35). All recurrent tumors displayed new
      quantitative genetic alterations and AR mutations, whatever the treatment
      modalities. AR amplification was found after complete blockade. Increased
      expression of Her-2/neu with frequent ERK/AKT activation was detected in all
      variants. Combination of castration with a Her-2/neu inhibitor decreased
      recurrence risk (0.17) and combination with an mTOR inhibitor prevented it. Anti
      hormone treatments influence risk of recurrence although tumor growth inhibition
      was initially similar. Recurrent tumors displayed genetic instability, AR
      mutations, and alterations of phosphorylation pathways. We postulated that Her
      2/AKT pathways allowed salvage of tumor cells under castration and we
      demonstrated that their inhibition prevented tumor recurrence in our model.

PMID- 22879925
TI  - TGF-beta sensitivity restrains CD8+ T cell homeostatic proliferation by enforcing
      sensitivity to IL-7 and IL-15.
AB  - The pleiotropic cytokine TGF-beta has been implicated in the regulation of
      numerous aspects of the immune response, including naive T cell homeostasis.
      Previous studies found that impairing TGF-beta responsiveness (through expression
      of a dominant-negative TGF-beta RII [DNRII] transgene) leads to accumulation of
      memory phenotype CD8 T cells, and it was proposed that this resulted from
      enhanced IL-15 sensitivity. Here we show naive DNRII CD8 T cells exhibit enhanced
      lymphopenia-driven proliferation and generation of "homeostatic" memory cells.
      However, this enhanced response occurred in the absence of IL-15 and,
      unexpectedly, even in the combined absence of IL-7 and IL-15, which were thought
      essential for CD8 T cell homeostatic expansion. DNRII transgenic CD8 T cells
      still require access to self Class I MHC for homeostatic proliferation, arguing
      against generalized dysregulation of homeostatic cues. These findings suggest TGF
      beta responsiveness is critical for enforcing sensitivity to homeostatic
      cytokines that limit maintenance and composition of the CD8 T cell pool. (154
      words).

PMID- 22879926
TI  - Prognostic impact of FoxP3+ regulatory T cells in relation to CD8+ T lymphocyte
      density in human colon carcinomas.
AB  - BACKGROUND: T-lymphocyte infiltration into colon carcinomas can influence
      clinical outcome, and interactions among T cell subsets may be more informative
      than either subset alone. Our objective was to examine the prognostic impact of
      tumor-infiltrating FoxP3(+) regulatory T cells (Tregs) in relation to cytotoxic
      CD8(+) T lymphocytes in patients with colon carcinomas characterized by DNA
      mismatch repair (MMR) status who participated in adjuvant chemotherapy trials.
      METHODS: FoxP3(+) and CD8(+) densities in tumor epithelial and stromal
      compartments were analyzed by immunohistochemistry and quantified in resected,
      stage II and III colonic carcinomas (N = 216). Immune marker density was
      dichotomized at the median and categorized as high vs low. MMR status was
      classified as MMR deficient (dMMR) or proficient (pMMR). Cox models were adjusted
      for age, stage, and tumor grade. RESULTS: The density of FoxP3+ infiltration was
      similar in tumor stroma and epithelia, whereas CD8+ was higher in stroma. The
      prognostic impact of FoxP3+ and CD8+ T cell infiltration was stronger in stroma
      vs epithelia, and the density of each marker in stroma was independently
      associated with improved overall survival (OS). However, the impact of FoxP3+ on
      survival was dependent upon CD8+ density (P interaction = 040). Among CD8+(low)
      tumors, FoxP3+(high) cases had significantly improved OS compared to FoxP3+(low)
      cases after adjustment for covariates (hazard ratio 0.43; 95% confidence interval
      0.19 to 0.95; P = .030). In contrast, FoxP3+ was not prognostic among CD8+(high)
      tumors. FoxP3+ remained prognostic in CD8+(low) tumors after further adjustment
      for MMR or BRAF(V600E) mutation status. Additionally, these immune markers
      identified a pMMR subgroup with a similarly favorable OS as for dMMR tumors.
      CONCLUSIONS: The prognostic impact of FoxP3+ and CD8+ T cell density are inter
      dependent, whereby FoxP3+ exerts a favorable influence on survival only in colon
      cancers with low CD8+ infiltration.

PMID- 22879927
TI  - Achieving maximal speed of solution exchange for patch clamp experiments.
AB  - BACKGROUND: Resolving the kinetics of agonist binding events separately from the
      subsequent channel gating processes requires the ability of applying and removing
      the agonist before channel gating occurs. No reported system has yet achieved
      pulses shorter than 100 us, necessary to study nicotinic ACh receptor or AMPA
      receptor activation. METHODOLOGY/PRINCIPAL FINDINGS: Solution exchange systems
      deliver short agonist pulses by moving a sharp interface between a control and an
      experimental solution across a channel preparation. We achieved shorter pulses by
      means of an exchange system that combines a faster flow velocity, narrower
      partition between the two streams, and increased velocity and bandwidth of the
      movement of the interface. The measured response of the entire system was fed
      back to optimize the voltage signal applied to the piezoelectric actuator
      overcoming the spurious oscillations arising from the mechanical resonances when
      a high bandwidth driving function was applied. Optimization was accomplished by
      analyzing the transfer function of the solution exchange system. When driven by
      optimized command pulses the enhanced system provided pulses lasting 26 +/- 1 us
      and exchanging 93 +/- 1% of the solution, as measured in the open tip of a patch
      pipette. CONCLUSIONS/SIGNIFICANCE: Pulses of this duration open the experimental
      study of the molecular events that occur between the agonist binding and the
      opening of the channel.

PMID- 22879928
TI  - Inhibition of TDP-43 accumulation by bis(thiosemicarbazonato)-copper complexes.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, motor neuron disease
      with no effective long-term treatment options. Recently, TDP-43 has been
      identified as a key protein in the pathogenesis of some cases of ALS. Although
      the role of TDP-43 in motor neuron degeneration is not yet known, TDP-43 has been
      shown to accumulate in RNA stress granules (SGs) in cell models and in spinal
      cord tissue from ALS patients. The SG association may be an early pathological
      change to TDP-43 metabolism and as such a potential target for therapeutic
      intervention. Accumulation of TDP-43 in SGs induced by inhibition of
      mitochondrial activity can be inhibited by modulation of cellular kinase
      activity. We have also found that treatment of cells and animal models of
      neurodegeneration, including an ALS model, with bioavailable
      bis(thiosemicarbazonato)copper(II) complexes (Cu(II)(btsc)s) can modulate kinase
      activity and induce neuroprotective effects. In this study we examined the effect
      of diacetylbis(-methylthiosemicarbazonato)copper(II) (Cu(II)(atsm)) and
      glyoxalbis(-methylthiosemicarbazonato)copper(II) (Cu(II)(gtsm)) on TDP-43
      positive SGs induced in SH-SY5Y cells in culture. We found that the Cu(II)(btsc)s
      blocked formation of TDP-43-and human antigen R (HuR)-positive SGs induced by
      paraquat. The Cu(II)(btsc)s protected neurons from paraquat-mediated cell death.
      These effects were associated with inhibition of ERK phosphorylation. Co
      treatment of cultures with either Cu(II)(atsm) or an ERK inhibitor, PD98059 both
      prevented ERK activation and blocked formation of TDP-43-and HuR-positive SGs.
      Cu(II)(atsm) treatment or ERK inhibition also prevented abnormal ubiquitin
      accumulation in paraquat-treated cells suggesting a link between prolonged ERK
      activation and abnormal ubiquitin metabolism in paraquat stress and inhibition by
      Cu. Moreover, Cu(II)(atsm) reduced accumulation of C-terminal (219-414) TDP-43 in
      transfected SH-SY5Y cells. These results demonstrate that Cu(II)(btsc) complexes
      could potentially be developed as a neuroprotective agent to modulate neuronal
      kinase function and inhibit TDP-43 aggregation. Further studies in TDP-43 animal
      models are warranted.

PMID- 22879929
TI  - beta-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis
      in intensive care unit patients: a randomized pilot study.
AB  - BACKGROUND: Invasive candidiasis (IC) is a devastating disease. While prompt
      antifungal therapy improves outcomes, empiric treatment based on the presence of
      fever has little clinical impact. Beta-D-Glucan (BDG) is a fungal cell wall
      component detectable in the serum of patients with early invasive fungal
      infection (IFI). We evaluated the utility of BDG surveillance as a guide for
      preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.
      METHODS: Patients admitted to the ICU for >= 3 days and expected to require at
      least 2 additional days of intensive care were enrolled. Subjects were randomized
      in 3:1 fashion to receive twice weekly BDG surveillance with preemptive
      anidulafungin in response to a positive test or empiric antifungal treatment
      based on physician preference. RESULTS: Sixty-four subjects were enrolled, with 1
      proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels
      were higher in subjects with proven/probable IC as compared to those without an
      IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2
      sequential BDG determinations of >= 80 pg/ml to define a positive test
      (sensitivity 100%, specificity 75%, positive predictive value 30%, negative
      predictive value 100%). In all, 21 preemptive and 5 empiric subjects received
      systemic antifungal therapy. Receipt of preemptive antifungal treatment had a
      significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was
      safe and generally well tolerated with excellent outcome. CONCLUSIONS: BDG
      monitoring may be useful for identifying ICU patients at highest risk to develop
      an IFI as well as for monitoring treatment response. Preemptive strategies based
      on fungal biomarkers warrant further study. TRIAL REGISTRATION: Clinical
      Trials.gov NCT00672841.

PMID- 22879930
TI  - Cross-reacting antibacterial auto-antibodies are produced within coronary
      atherosclerotic plaques of acute coronary syndrome patients.
AB  - Coronary atherosclerosis, the main condition predisposing to acute myocardial
      infarction, has an inflammatory component caused by stimuli that are yet unknown.
      We molecularly investigated the nature of the immune response within human
      coronary lesion in four coronary plaques obtained by endoluminal atherectomy from
      four patients. We constructed phage-display libraries containing the IgG1/kappa
      antibody fragments produced by B-lymphocytes present in each plaque. By
      immunoaffinity, we selected from these libraries a monoclonal antibody,
      arbitrarily named Fab7816, able to react both with coronary and carotid
      atherosclerotic tissue samples. We also demonstrated by confocal microscopy that
      this monoclonal antibody recognized human transgelin type 1, a cytoskeleton
      protein involved in atherogenesis, and that it co-localized with fibrocyte-like
      cells transgelin+, CD68+, CD45+ in human sections of coronary and carotid
      plaques. In vitro fibrocytes obtained by differentiating CD14+ cells isolated
      from peripheral blood mononuclear cells also interacted with Fab7816, thus
      supporting the hypothesis of a specific recognition of fibrocytes into the
      atherosclerotic lesions. Interestingly, the same antibody, cross-reacted with the
      outer membrane proteins of Proteus mirabilis and Klebsiella pneumoniae (and
      possibly with homologous proteins of other enterobacteriaceae present in the
      microbiota). From all the other three libraries, we were able to clone, by
      immunoaffinity selection, human monoclonal antibodies cross-reacting with
      bacterial outer membrane proteins and with transgelin. These findings
      demonstrated that in human atherosclerotic plaques a local cross-reactive immune
      response takes place.

PMID- 22879931
TI  - Arbitrary symbolism in natural language revisited: when word forms carry meaning.
AB  - Cognitive science has a rich history of interest in the ways that languages
      represent abstract and concrete concepts (e.g., idea vs. dog). Until recently,
      this focus has centered largely on aspects of word meaning and semantic
      representation. However, recent corpora analyses have demonstrated that abstract
      and concrete words are also marked by phonological, orthographic, and
      morphological differences. These regularities in sound-meaning correspondence
      potentially allow listeners to infer certain aspects of semantics directly from
      word form. We investigated this relationship between form and meaning in a series
      of four experiments. In Experiments 1-2 we examined the role of metalinguistic
      knowledge in semantic decision by asking participants to make semantic judgments
      for aurally presented nonwords selectively varied by specific acoustic and
      phonetic parameters. Participants consistently associated increased word length
      and diminished wordlikeness with abstract concepts. In Experiment 3, participants
      completed a semantic decision task (i.e., abstract or concrete) for real words
      varied by length and concreteness. Participants were more likely to misclassify
      longer, inflected words (e.g., "apartment") as abstract and shorter uninflected
      abstract words (e.g., "fate") as concrete. In Experiment 4, we used a multiple
      regression to predict trial level naming data from a large corpus of nouns which
      revealed significant interaction effects between concreteness and word form.
      Together these results provide converging evidence for the hypothesis that
      listeners map sound to meaning through a non-arbitrary process using prior
      knowledge about statistical regularities in the surface forms of words.

PMID- 22879932
TI  - Bispecific engineered antibody domains (nanoantibodies) that interact
      noncompetitively with an HIV-1 neutralizing epitope and FcRn.
AB  - Libraries based on an isolated human immunoglobulin G1 (IgG1) constant domain 2
      (CH2) have been previously diversified by random mutagenesis. However, native
      isolated CH2 is not very stable and the generation of many mutations could lead
      to an increase in immunogenicity. Recently, we demonstrated that engineering an
      additional disulfide bond and removing seven N-terminal residues results in an
      engineered antibody domain (eAd) (m01s) with highly increased stability and
      enhanced binding to human neonatal Fc receptor (FcRn) (Gong et al, JBC, 2009 and
      2011). We and others have also previously shown that grafting of the heavy chain
      complementarity region 3 (CDR-H3 (H3)) onto cognate positions of the variable
      domain leads to highly diversified libraries from which a number of binders to
      various antigens have been selected. However, grafting of H3s to non-cognate
      positions in constant domains results in additional residues at the junctions of
      H3s and the CH2 framework. Here we describe a new method based on multi-step PCR
      that allows the precise replacement of loop FG (no changes in its flanking
      sequences) by human H3s from another library. Using this method and limited
      mutagenesis of loops BC and DE we generated an eAd phage-displayed library.
      Panning of this library against an HIV-1 gp41 MPER peptide resulted in selection
      of a binder, m2a1, which neutralized HIV-1 isolates from different clades with
      modest activity and retained the m01s capability of binding to FcRn. This result
      provides a proof of concept that CH2-based antigen binders that also mimic to
      certain extent other functions of full-size antibodies (binding to FcRn) can be
      generated; we have previously hypothesized that such binders can be made and
      coined the term nanoantibodies (nAbs). Further studies in animal models and in
      humans will show how useful nAbs could be as therapeutics and diagnostics.

PMID- 22879933
TI  - c-Abl is an upstream regulator of acid sphingomyelinase in apoptosis induced by
      inhibition of integrins alphavbeta3 and alphavbeta5.
AB  - Inhibition of integrins alphavbeta3/alphavbeta5 by the cyclic function-blocking
      peptide, RGDfV (Arg-Gly-Asp-Phe-Val) can induce apoptosis in both normal cells
      and tumor cells. We show that RGDfV induced apoptosis in ECV-304 carcinoma cells,
      increased activity and mRNA expression of acid sphingomyelinase (ASM), and
      increased ceramides C(16), C(18:0), C(24:0) and C(24:1) while decreasing the
      corresponding sphingomyelins. siRNA to ASM decreased RGDfV-induced apoptosis as
      measured by TUNEL, PARP cleavage, mitochondrial depolarization, and caspase-3 and
      caspase-8 activities, as well as by annexinV in a 3D collagen model. These
      findings indicate a causal role for ASM in RGDfV-induced apoptosis in ECV-304. We
      have shown that c-Abl, a non-receptor tyrosine kinase, also mediates RGDfV
      induced apoptosis. However, c-Abl, has not been previously linked to ASM in any
      system. Here we show that STI-571 (imatinib, inhibitor of c-Abl) inhibited RGDfV
      induced ASM activity. Furthermore, STI-571 and c-Abl-siRNA both inhibited RGDfV
      induced increase in ASM mRNA, but ASM-siRNA did not affect c-Abl phosphorylation
      or expression, supporting that c-Abl regulates the RGDfV-induced increase in ASM
      expression. These studies implicate ASM as a mediator of apoptosis induced by
      inhibition of integrins alphavbeta3/alphavbeta5, and for the first time place c
      Abl as an upstream regulator of ASM expression and activity.

PMID- 22879934
TI  - Relationship between swim bladder morphology and hearing abilities--a case study
      on Asian and African cichlids.
AB  - BACKGROUND: Several teleost species have evolved anterior extensions of the swim
      bladder which come close to or directly contact the inner ears. A few comparative
      studies have shown that these morphological specializations may enhance hearing
      abilities. This study investigates the diversity of swim bladder morphology in
      four Asian and African cichlid species and analyzes how this diversity affects
      their hearing sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: We studied swim
      bladder morphology by dissections and by making 3D reconstructions from high
      resolution microCT scans. The auditory sensitivity was determined in terms of
      sound pressure levels (SPL) and particle acceleration levels (PAL) using the
      auditory evoked potential (AEP) recording technique. The swim bladders in
      Hemichromis guttatus and Steatocranus tinanti lacked anterior extensions and the
      swim bladder was considerably small in the latter species. In contrast,
      Paratilapia polleni and especially Etroplus maculatus possessed anterior
      extensions bringing the swim bladder close to the inner ears. All species were
      able to detect frequencies up to 3 kHz (SPL) except S. tinanti which only
      responded to frequencies up to 0.7 kHz. P. polleni and E. maculatus showed
      significantly higher auditory sensitivities at 0.5 and 1 kHz than the two species
      lacking anterior swim bladder extensions. The highest auditory sensitivities were
      found in E. maculatus, which possessed the most intimate swim bladder-inner ear
      relationship (maximum sensitivity 66 dB re 1 uPa at 0.5 kHz). CONCLUSIONS: Our
      results indicate that anterior swim bladder extensions seem to improve mean
      absolute auditory sensitivities by 21-42 dB (SPLs) and 21-36 dB (PALs) between
      0.5 and 1 kHz. Besides anterior extensions, the size of the swim bladder appears
      to be an important factor for extending the detectable frequency range (up to 3
      kHz).

PMID- 22879935
TI  - Markov models of use-dependence and reverse use-dependence during the mouse
      cardiac action potential.
AB  - The fast component of the cardiac transient outward current, I(Ktof), is blocked
      by a number of drugs. The major molecular bases of I(Ktof) are Kv4.2/Kv4.3
      voltage-gated potassium channels. Drugs with similar potencies but different
      blocking mechanisms have differing effects on action potential duration (APD). We
      used in silico analysis to determine the effect of I(Ktof)-blocking drugs with
      different blocking mechanisms on mouse ventricular myocytes. We used our existing
      mouse model of the action potential, and developed 4 new Markov formulations for
      I(Ktof), I(Ktos), I(Kur), I(Ks). We compared effects of theoretical I(Ktof)
      specific channel blockers: (1) a closed state, and (2) an open channel blocker.
      At concentrations lower or close to IC(50), the drug which bound to the open
      state always had a much greater effect on APD than the drug which bound to the
      closed state. At concentrations much higher than IC(50), both mechanisms had
      similar effects at very low pacing rates. However, an open state binding drug had
      a greater effect on APD at faster pacing rates, particularly around 10 Hz. In
      summary, our data indicate that drug effects on APD are strongly dependent not
      only on IC(50), but also on the drug binding state.

PMID- 22879936
TI  - ZFX controls the self-renewal of human embryonic stem cells.
AB  - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer
      great promise in regenerative medicine and disease modeling due to their
      unlimited self-renewal and broad differentiation capacity. There is evidence that
      the growth properties and critical signaling pathways differ between murine and
      human ESCs; therefore, it is essential to perform functional studies to test the
      putatively conserved mechanisms of pluripotent stem cell self-renewal between
      species. Previously, we identified the transcription factor Zfx as a key
      regulator of self-renewal in murine ESCs. Here we extend those findings to human
      ESCs. ZFX knockdown in hESCs hindered clonal growth and decreased colony size
      after serial replating. ZFX overexpression enhanced clone formation in the
      presence of Y-27632, increased colony size at low density and decreased
      expression of differentiation-related genes in human ESCs. ZFX-overexpressing
      hESCs resisted spontaneous differentiation but could be directed to differentiate
      into endodermal and neural cell fates when provided with the appropriate cues.
      Thus, ZFX acts as a molecular rheostat regulating the balance between self
      renewal and differentiation in hESCs, revealing the close evolutionary
      conservation of the self-renewal mechanisms in murine and human ESCs.

PMID- 22879937
TI  - Comparative transcriptomics of H. pylori strains AM5, SS1 and their hpyAVIBM
      deletion mutants: possible roles of cytosine methylation.
AB  - Helicobacter pylori is an important human pathogen and one of the most successful
      chronic colonizers of the human body. H. pylori uses diverse mechanisms to
      modulate its interaction with the host in order to promote chronic infection and
      overcome host immune response. Restriction-modification genes are a major part of
      strain-specific genes present in H. pylori. The role of N(6)--adenine methylation
      in bacterial gene regulation and virulence is well established but not much is
      known about the effect of C(5) -cytosine methylation on gene expression in
      prokaryotes. In this study, it was observed by microarray analysis and RT-PCR,
      that deletion of an orphan C(5) -cytosine methyltransferase, hpyAVIBM in H.
      pylori strains AM5and SS1 has a significant effect on the expression of number of
      genes belonging to motility, adhesion and virulence. AM5DeltahpyAVIBM mutant
      strain has a different LPS profile and is able to induce high IL-8 production
      compared to wild-type. hpyAVIBM from strain 26695 is able to complement mutant
      SS1 and AM5 strains. This study highlights a possible significance of cytosine
      methylation in the physiology of H. pylori.

PMID- 22879938
TI  - Carboxyamidotriazole-orotate inhibits the growth of imatinib-resistant chronic
      myeloid leukaemia cells and modulates exosomes-stimulated angiogenesis.
AB  - The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous
      leukaemia (CML) by imatinib mesylate. While imatinib has been extremely effective
      for chronic phase CML, blast crisis CML are often resistant. New therapeutic
      options are therefore needed for this fatal disease. Although more common in
      solid tumors, increased microvessel density was also reported in chronic
      myelogenous leukaemia and was associated with a significant increase of
      angiogenic factors, suggesting that vascularity in hematologic malignancies is a
      controlled process and may play a role in the leukaemogenic process thus
      representing an alternative therapeutic target. Carboxyamidotriazole-orotate
      (CTO) is the orotate salt form of carboxyamidotriazole (CAI), an orally
      bioavailable signal transduction inhibitor that in vitro has been shown to
      possess antileukaemic activities. CTO, which has a reduced toxicity, increased
      oral bioavailability and stronger efficacy when compared to the parental
      compound, was tested in this study for its ability to affect imatinib-resistant
      CML tumor growth in a xenograft model. The active cross talk between endothelial
      cells and leukemic cells in the bone marrow involving exosomes plays an important
      role in modulating the process of neovascularization in CML. We have thus
      investigated the effects of CTO on exosome-stimulated angiogenesis. Our results
      indicate that CTO may be effective in targeting both cancer cell growth and the
      tumor microenvironment, thus suggesting a potential therapeutic utility for CTO
      in leukaemia patients.

PMID- 22879940
TI  - Inbreeding alters activities of the stress-related enzymes chitinases and beta
      1,3-glucanases.
AB  - Pathogenesis-related proteins, chitinases (CHT) and beta-1,3-glucanases (GLU),
      are stress proteins up-regulated as response to extrinsic environmental stress in
      plants. It is unknown whether these PR proteins are also influenced by
      inbreeding, which has been suggested to constitute intrinsic genetic stress, and
      which is also known to affect the ability of plants to cope with environmental
      stress. We investigated activities of CHT and GLU in response to inbreeding in
      plants from 13 Ragged Robin (Lychnis flos-cuculi) populations. We also studied
      whether activities of these enzymes were associated with levels of herbivore
      damage and pathogen infection in the populations from which the plants
      originated. We found an increase in pathogenesis-related protein activity in
      inbred plants from five out of the 13 investigated populations, which suggests
      that these proteins may play a role in how plants respond to intrinsic genetic
      stress brought about by inbreeding in some populations depending on the allele
      frequencies of loci affecting the expression of CHT and the past levels of
      inbreeding. More importantly, we found that CHT activities were higher in plants
      from populations with higher levels of herbivore or pathogen damage, but
      inbreeding reduced CHT activity in these populations disrupting the increased
      activities of this resistance-related enzyme in populations where high resistance
      is beneficial. These results provide novel information on the effects of plant
      inbreeding on plant-enemy interactions on a biochemical level.

PMID- 22879939
TI  - TGFbeta-stimulated microRNA-21 utilizes PTEN to orchestrate AKT/mTORC1 signaling
      for mesangial cell hypertrophy and matrix expansion.
AB  - Transforming growth factor-beta (TGFbeta) promotes glomerular hypertrophy and
      matrix expansion, leading to glomerulosclerosis. MicroRNAs are well suited to
      promote fibrosis because they can repress gene expression, which negatively
      regulate the fibrotic process. Recent cellular and animal studies have revealed
      enhanced expression of microRNA, miR-21, in renal cells in response to TGFbeta.
      Specific miR-21 targets downstream of TGFbeta receptor activation that control
      cell hypertrophy and matrix protein expression have not been studied. Using 3'UTR
      driven luciferase reporter, we identified the tumor suppressor protein PTEN as a
      target of TGFbeta-stimulated miR-21 in glomerular mesangial cells. Expression of
      miR-21 Sponge, which quenches endogenous miR-21 levels, reversed TGFbeta-induced
      suppression of PTEN. Additionally, miR-21 Sponge inhibited TGFbeta-stimulated
      phosphorylation of Akt kinase, resulting in attenuation of phosphorylation of its
      substrate GSK3beta. Tuberin and PRAS40, two other Akt substrates, and endogenous
      inhibitors of mTORC1, regulate mesangial cell hypertrophy. Neutralization of
      endogenous miR-21 abrogated TGFbeta-stimulated phosphorylation of tuberin and
      PRAS40, leading to inhibition of phosphorylation of S6 kinase, mTOR and 4EBP-1.
      Moreover, downregulation of miR-21 significantly suppressed TGFbeta-induced
      protein synthesis and hypertrophy, which were reversed by siRNA-targeted
      inhibition of PTEN expression. Similarly, expression of constitutively active Akt
      kinase reversed the miR-21 Sponge-mediated inhibition of TGFbeta-induced protein
      synthesis and hypertrophy. Furthermore, expression of constitutively active
      mTORC1 prevented the miR-21 Sponge-induced suppression of mesangial cell protein
      synthesis and hypertrophy by TGFbeta. Finally, we show that miR-21 Sponge
      inhibited TGFbeta-stimulated fibronectin and collagen expression. Suppression of
      PTEN expression and expression of both constitutively active Akt kinase and
      mTORC1 independently reversed this miR-21-mediated inhibition of TGFbeta-induced
      fibronectin and collagen expression. Our results uncover an essential role of
      TGFbeta-induced expression of miR-21, which targets PTEN to initiate a non
      canonical signaling circuit involving Akt/mTORC1 axis for mesangial cell
      hypertrophy and matrix protein synthesis.

PMID- 22879941
TI  - Protective roles of DMP1 in high phosphate homeostasis.
AB  - PURPOSE: Dmp1 (dentin matrix protein1) null mice (Dmp1(-/-)) display
      hypophosphatemic rickets with a sharp increase in fibroblast growth factor 23
      (FGF23). Disruption of Klotho (the obligatory co-receptor of FGF23) results in
      hyperphosphatemia with ectopic calcifications formed in blood vessels and
      kidneys. To determine the role of DMP1 in both a hyperphosphatemic environment
      and within the ectopic calcifications, we created Dmp1/Klotho compound deficient
      (Dmp1(-/-)kl/kl) mice. PROCEDURES: A combination of TUNEL, immunohistochemistry,
      TRAP, von Kossa, micro CT, bone histomorphometry, serum biochemistry and Scanning
      Electron Microscopy techniques were used to analyze the changes in blood vessels,
      kidney and bone for wild type control, Dmp1(-/-), Klotho deficient (kl/kl) and
      Dmp1(-/-)kl/kl animals. FINDINGS: Interestingly, Dmp1(-/-)kl/kl mice show a
      dramatic improvement of rickets and an identical serum biochemical phenotype to
      kl/kl mice (extremely high FGF23, hyperphosphatemia and reduced parathyroid
      hormone (PTH) levels). Unexpectedly, Dmp1(-/-)kl/kl mice presented elevated
      levels of apoptosis in osteocytes, endothelial and vascular smooth muscle cells
      in small and large blood vessels, and within the kidney as well as dramatic
      increase in ectopic calcification in all these tissues, as compared to kl/kl.
      CONCLUSION: These findings suggest that DMP1 has an anti-apoptotic role in
      hyperphosphatemia. Discovering this novel protective role of DMP1 may have
      clinical relevance in protecting the cells from apoptosis in high-phosphate
      environments as observed in chronic kidney disease (CKD).

PMID- 22879942
TI  - Differences in neural-immune gene expression response in rat spinal dorsal horn
      correlates with variations in electroacupuncture analgesia.
AB  - BACKGROUND: Electroacupuncture (EA) has been widely used to alleviate diverse
      pains. Accumulated clinical experiences and experimental observations indicated
      that significant differences exist in sensitivity to EA analgesia for individuals
      of patients and model animals. However, the molecular mechanism accounting for
      this difference remains obscure. METHODOLOGY/PRINCIPAL FINDINGS: We classified
      model male rats into high-responder (HR; TFL changes >150) and non-responder (NR;
      TFL changes <= 0) groups based on changes of their pain threshold detected by
      tail-flick latency (TFL) before and after 2 Hz or 100 Hz EA treatment. Gene
      expression analysis of spinal dorsal horn (DH) revealed divergent expression in
      HR and NR after 2 Hz/100 Hz EA. The expression of the neurotransmitter system
      related genes was significantly highly regulated in the HR animals while the
      proinflammation cytokines related genes were up-regulated more significantly in
      NR than that in HR after 2 Hz and 100 Hz EA stimulation, especially in the case
      of 2 Hz stimulation. CONCLUSIONS/SIGNIFICANCE: Our results suggested that
      differential regulation and coordination of neural-immune related genes might
      play an important role for individual variations in analgesic effects responding
      to EA in DH. It also provided new candidate genes related to EA responsiveness
      for future investigation.

PMID- 22879943
TI  - Productivity cost due to maternal ill health in Sri Lanka.
AB  - BACKGROUND: The global impact of maternal ill health on economic productivity is
      estimated to be over 15 billion USD per year. Global data on productivity cost
      associated with maternal ill health are limited to estimations based on secondary
      data. Purpose of our study was to determine the productivity cost due to maternal
      ill health during pregnancy in Sri Lanka. METHODS AND FINDINGS: We studied 466
      pregnant women, aged 24 to 36 weeks, residing in Anuradhapura, Sri Lanka. A two
      stage cluster sampling procedure was used in a cross sectional design and all
      pregnant women were interviewed at clinic centers, using the culturally adapted
      Immpact tool kit for productivity cost assessment. Of the 466 pregnant women
      studied, 421 (90.3%) reported at least one ill health condition during the
      pregnancy period, and 353 (83.8%) of them had conditions affecting their daily
      life. Total incapacitation requiring another person to carry out all their
      routine activities was reported by 122 (26.1%) of the women. In this study
      sample, during the last episode of ill health, total number of days lost due to
      absenteeism was 3,356 (32.9% of total loss) and the days lost due to presenteeism
      was 6,832.8 (67.1% of the total loss). Of the 353 women with ill health
      conditions affecting their daily life, 280 (60%) had coping strategies to recover
      loss of productivity. Of the coping strategies used to recover productivity loss
      during maternal ill health, 76.8% (n = 215) was an intra-household adaptation,
      and 22.8% (n = 64) was through social networks. Loss of productivity was 28.9
      days per episode of maternal ill health. The mean productivity cost due to last
      episode of ill health in this sample was Rs.8,444.26 (95% CI-Rs.6888.74
      Rs.9999.78). CONCLUSIONS: Maternal ill health has a major impact on household
      productivity and economy. The major impact is due to, generally ignored minor
      ailments during pregnancy.

PMID- 22879944
TI  - Relating the disease mutation spectrum to the evolution of the cystic fibrosis
      transmembrane conductance regulator (CFTR).
AB  - Cystic fibrosis (CF) is the most common genetic disease among Caucasians, and
      accordingly the cystic fibrosis transmembrane conductance regulator (CFTR)
      protein has perhaps the best characterized disease mutation spectrum with more
      than 1,500 causative mutations having been identified. In this study, we took
      advantage of that wealth of mutational information in an effort to relate site
      specific evolutionary parameters with the propensity and severity of CFTR disease
      causing mutations. To do this, we devised a scoring scheme for known CFTR disease
      causing mutations based on the Grantham amino acid chemical difference matrix.
      CFTR site-specific evolutionary constraint values were then computed for seven
      different evolutionary metrics across a range of increasing evolutionary depths.
      The CFTR mutational scores and the various site-specific evolutionary constraint
      values were compared in order to evaluate which evolutionary measures best
      reflect the disease-causing mutation spectrum. Site-specific evolutionary
      constraint values from the widely used comparative method PolyPhen2 show the best
      correlation with the CFTR mutation score spectrum, whereas more straightforward
      conservation based measures (ConSurf and ScoreCons) show the greatest ability to
      predict individual CFTR disease-causing mutations. While far greater than could
      be expected by chance alone, the fraction of the variability in mutation scores
      explained by the PolyPhen2 metric (3.6%), along with the best set of paired
      sensitivity (58%) and specificity (60%) values for the prediction of disease
      causing residues, were marginal. These data indicate that evolutionary constraint
      levels are informative but far from determinant with respect to disease-causing
      mutations in CFTR. Nevertheless, this work shows that, when combined with
      additional lines of evidence, information on site-specific evolutionary
      conservation can and should be used to guide site-directed mutagenesis
      experiments by more narrowly defining the set of target residues, resulting in a
      potential savings of both time and money.

PMID- 22879945
TI  - Quantitative normative gait data in a large cohort of ambulatory persons with
      Parkinson's disease.
AB  - BACKGROUND: Gait performance is widely evaluated to assess health status in older
      adult populations. While several investigators have presented normative values
      for spatiotemporal gait parameters drawn from older adult populations, the
      literature has been void of large-scale cohort studies, which are needed in order
      to provide quantitative, normative gait data in persons with Parkinson's disease.
      The aim of this investigation was to provide reference values for clinically
      important gait characteristics in a large sample of ambulatory persons with
      Parkinson's disease to aid both clinicians and researchers in their evaluations
      and treatments of gait impairment. METHODOLOGY/PRINCIPAL FINDINGS: Gait
      performance was collected in 310 individuals with idiopathic Parkinson's disease
      as they walked across a pressure sensitive walkway. Fourteen quantitative gait
      parameters were measured and evaluated with respect to Hoehn and Yahr disease
      staging and gender. Disease duration and age were controlled for in all analyses.
      Individuals with the greatest Parkinson's disability walked significantly slower
      with shorter steps and stride lengths than the mild and moderately affected
      groups. Further, the most affected patients spent more time with both feet on the
      ground, and walked with a wider base of support than the moderately disabled
      patients. No differences were detected between the mild and moderate disability
      groups on any of the gait parameters evaluated. CONCLUSIONS/SIGNIFICANCE:
      Reference values for 14 gait parameters in a large cohort of ambulatory patients
      with Parkinson's disease are provided and these may be highly useful for
      assessing and interpreting an individual's gait dysfunction. It is important for
      clinicians and researchers to appreciate the lack of change in quantitative
      parameters as PD patients move from mild to moderate gait impairment.

PMID- 22879946
TI  - Estimating point and interval frequency of antigen-specific CD4+ T cells based on
      short in vitro expansion and improved poisson distribution analysis.
AB  - BACKGROUND: Knowledge of antigen-specific CD4(+) T cells frequencies is pivotal
      to the choice of the antigen to be used in anti-viral and anti-tumor vaccination
      procedures and for monitoring of immune responses. Methods that employ small cell
      numbers from patient samples, are easy to perform and do not require complex
      techniques/instrumentations and therefore standardization are desirable.
      METHODOLOGY/PRINCIPAL FINDINGS: Purified blood CD4(+) T cells from healthy donors
      were cultured with autologous antigen presenting cells in several replicate wells
      in equal numbers in the absence (un-stimulated wells) or in the presence of
      synthetic peptides corresponding to viral antigens promiscuous HLA-DR epitopes
      (antigen-stimulated wells). At day 7 of culture low dose IL-2 was added and at
      day 14 IFN-gamma and IL-5 release in the supernatant was measured. A statistical
      analysis approach, based on Poisson distribution, was then implemented to
      calculate the frequency of viral-specific CD4(+) T cells. We first determined a
      patient-specific exceptionality threshold of cytokine release in the un
      stimulated wells and then, based on this threshold, we counted the
      inactive/active wells within the antigen-stimulated wells. This number, along
      with the number of cells per well, allowed the point and interval estimates of
      frequencies. A ready-to-use Excel worksheet template with automatic calculations
      for frequencies estimate was developed and is provided as a supplemental file
      (Table S9). CONCLUSIONS/SIGNIFICANCE: We report a simple experimental procedure
      combining short term in vitro cell culture with statistical analysis to calculate
      the frequency of antigen-specific CD4(+) T cells. The detailed experimental
      procedure along with the Excel applicative are a valuable tool for monitoring
      immune responses in the clinical practice.

PMID- 22879947
TI  - Fractionated therapy of HER2-expressing breast and ovarian cancer xenografts in
      mice with targeted alpha emitting 227Th-DOTA-p-benzyl-trastuzumab.
AB  - BACKGROUND: The aim of this study was to investigate therapeutic efficacy and
      normal tissue toxicity of single dosage and fractionated targeted alpha therapy
      (TAT) in mice with HER2-expressing breast and ovarian cancer xenografts using the
      low dose rate radioimmunoconjugate (227)Th-DOTA-p-benzyl-trastuzumab.
      METHODOLOGY/PRINCIPAL FINDINGS: Nude mice carrying HER2-overexpressing
      subcutaneous SKOV-3 or SKBR-3 xenografts were treated with 1000 kBq/kg (227)Th
      trastuzumab as single injection or four injections of 250 kBq/kg with intervals
      of 4-5 days, 2 weeks, or 4 weeks. Control animals were treated with normal saline
      or unlabeled trastuzumab. In SKOV-3 xenografts tumor growth to 10-fold size was
      delayed (p<0.01) and survival with tumor diameter less than 16 mm was prolonged
      (p<0.05) in all TAT groups compared to the control groups. No statistically
      significant differences were seen among the treated groups. In SKBR-3 xenografts
      tumor growth to 10-fold size was delayed in the single injection and 4-5 days
      interval groups (p<0.001) and all except the 4 weeks interval TAT group showed
      improved survival to the control groups (p<0.05). Toxicity was assessed by blood
      cell counts, clinical chemistry measurements and body weight. Transient reduction
      in white blood cells was seen for the single injection and 4-5 days interval
      groups (p<0.05). No significant changes were seen in red blood cells, platelets
      or clinical chemistry parameters. Survival without life threatening loss of body
      weight was significantly prolonged in 4 weeks interval group compared to single
      injection group (p<0.05) for SKOV-3 animals and in 2 weeks interval group
      compared with the 4-5 days interval groups (p<0.05) for SKBR-3 animals.
      CONCLUSIONS/SIGNIFICANCE: The same concentration of radioactivity split into
      several fractions may improve toxicity of (227)Th-radioimmunotherapy while the
      therapeutic effect is maintained. Thus, it might be possible to increase the
      cumulative absorbed radiation dose to tumor with acceptable toxicity by
      fractionation of the dosage.

PMID- 22879949
TI  - Understanding the basis of drug resistance of the mutants of alphabeta-tubulin
      dimer via molecular dynamics simulations.
AB  - The vital role of tubulin dimer in cell division makes it an attractive drug
      target. Drugs that target tubulin showed significant clinical success in treating
      various cancers. However, the efficacy of these drugs is attenuated by the
      emergence of tubulin mutants that are unsusceptible to several classes of tubulin
      binding drugs. The molecular basis of drug resistance of the tubulin mutants is
      yet to be unraveled. Here, we employ molecular dynamics simulations, protein
      ligand docking, and MMPB(GB)SA analyses to examine the binding of anticancer
      drugs, taxol and epothilone to the reported point mutants of tubulin--T274I,
      R282Q, and Q292E. Results suggest that the mutations significantly alter the
      tubulin structure and dynamics, thereby weaken the interactions and binding of
      the drugs, primarily by modifying the M loop conformation and enlarging the
      pocket volume. Interestingly, these mutations also affect the tubulin distal
      sites that are associated with microtubule building processes.

PMID- 22879948
TI  - fussel (fuss)--A negative regulator of BMP signaling in Drosophila melanogaster.
AB  - The TGF-beta/BMP signaling cascades control a wide range of developmental and
      physiological functions in vertebrates and invertebrates. In Drosophila
      melanogaster, members of this pathway can be divided into a Bone Morphogenic
      Protein (BMP) and an Activin-beta (Act-beta) branch, where Decapentaplegic (Dpp),
      a member of the BMP family has been most intensively studied. They differ in
      ligands, receptors and transmitting proteins, but also share some components,
      such as the Co-Smad Medea (Med). The essential role of Med is to form a complex
      with one of the two activating Smads, mothers against decapentaplegic (Mad) or
      dSmad, and to translocate together to the nucleus where they can function as
      transcriptional regulators of downstream target genes. This signaling cascade
      underlies different mechanisms of negative regulation, which can be exerted by
      inhibitory Smads, such as daughters against decapentaplegic (dad), but also by
      the Ski-Sno family. In this work we identified and functionally analyzed a new
      member of the Ski/Sno-family, fussel (fuss), the Drosophila homolog of the human
      functional suppressing element 15 (fussel-15). fuss codes for two differentially
      spliced transcripts with a neuronal expression pattern. The proteins are
      characterized by a Ski-Sno and a SAND homology domain. Overexpression studies and
      genetic interaction experiments clearly reveal an interaction of fuss with
      members of the BMP pathway, leading to a strong repression of BMP-signaling. The
      protein interacts directly with Medea and seems to reprogram the Smad pathway
      through its influence upon the formation of functional Mad/Medea complexes. This
      leads amongst others to a repression of downstream target genes of the Dpp
      pathway, such as optomotor blind (omb). Taken together we could show that fuss
      exerts a pivotal role as an antagonist of BMP signaling in Drosophila
      melanogaster.

PMID- 22879950
TI  - Temporal-spatial variation and controls of soil respiration in different primary
      succession stages on glacier forehead in Gongga Mountain, China.
AB  - Soil respiration (SR) is an important process in the global carbon cycle. It is
      difficult to estimate SR emission accurately because of its temporal and spatial
      variability. Primary forest succession on Glacier forehead provides the ideal
      environment for examining the temporal-spatial variation and controlling factors
      of SR. However, relevant studies on SR are relatively scarce, and variations, as
      well as controlling factors, remain uncertain in this kind of region. In this
      study, we used a static chamber system to measure SR in six sites which represent
      different stages of forest succession on forehead of a temperate glacier in
      Gongga Mountain, China. Our results showed that there was substantial temporal
      (coefficient of variation (CV) ranged from 39.3% to 73.9%) and spatial (CV ranged
      from 12.3% to 88.6%) variation in SR. Soil temperature (ST) at 5 cm depth was the
      major controlling factor of temporal variation in all six sites. Spatial
      variation in SR was mainly caused by differences in plant biomass and Total N
      among the six sites. Moreover, soil moisture (SM), microbial biomass carbon
      (MBC), soil organic carbon (SOC), pH and bulk density could influence SR by
      directly or indirectly affecting plant biomass and Total N. Q(10) values (ranged
      from 2.1 to 4.7) increased along the forest succession, and the mean value (3.3)
      was larger than that of temperate ecosystems, which indicated a general tendency
      towards higher-Q(10) in colder ecosystems than in warmer ecosystems. Our findings
      provided valuable information for understanding temporal-spatial variation and
      controlling factors of SR.

PMID- 22879951
TI  - A VLP vaccine induces broad-spectrum cross-protective antibody immunity against
      H5N1 and H1N1 subtypes of influenza A virus.
AB  - The recent threats of influenza epidemics and pandemics have prioritized the
      development of a universal vaccine that offers protection against a wider variety
      of influenza infections. Here, we demonstrate a genetically modified virus-like
      particle (VLP) vaccine, referred to as H5M2eN1-VLP, that increased the antigenic
      content of NA and induced rapid recall of antibody against HA(2) after viral
      infection. As a result, H5M2eN1-VLP vaccination elicited a broad humoral immune
      response against multiple viral proteins and caused significant protection
      against homologous RG-14 (H5N1) and heterologous A/California/07/2009 H1N1
      (CA/07) and A/PR/8/34 H1N1 (PR8) viral lethal challenges. Moreover, the N1-VLP
      (lacking HA) induced production of a strong NA antibody that also conferred
      significant cross protection against H5N1 and heterologous CA/07 but not PR8,
      suggesting the protection against N1-serotyped viruses can be extended from avian
      origin to CA/07 strain isolated in humans, but not to evolutionally distant
      strains of human-derived. By comparative vaccine study of an HA-based VLP (H5N1
      VLP) and NA-based VLPs, we found that H5N1-VLP vaccination induced specific and
      strong protective antibodies against the HA(1) subunit of H5, thus restricting
      the breadth of cross-protection. In summary, we present a feasible example of
      direction of VLP vaccine immunity toward NA and HA(2), which resulted in cross
      protection against both seasonal and pandemic influenza strains, that could form
      the basis for future design of a better universal vaccine.

PMID- 22879952
TI  - WSC-1 and HAM-7 are MAK-1 MAP kinase pathway sensors required for cell wall
      integrity and hyphal fusion in Neurospora crassa.
AB  - A large number of cell wall proteins are encoded in the Neurospora crassa genome.
      Strains carrying gene deletions of 65 predicted cell wall proteins were
      characterized. Deletion mutations in two of these genes (wsc-1 and ham-7) have
      easily identified morphological and inhibitor-based defects. Their phenotypic
      characterization indicates that HAM-7 and WSC-1 function during cell-to-cell
      hyphal fusion and in cell wall integrity maintenance, respectively. wsc-1 encodes
      a transmembrane protein with extensive homology to the yeast Wsc family of sensor
      proteins. In N. crassa, WSC-1 (and its homolog WSC-2) activates the cell wall
      integrity MAK-1 MAP kinase pathway. The GPI-anchored cell wall protein HAM-7 is
      required for cell-to-cell fusion and the sexual stages of the N. crassa life
      cycle. Like WSC-1, HAM-7 is required for activating MAK-1. A Deltawsc-1;Deltaham
      7 double mutant fully phenocopies mutants lacking components of the MAK-1 MAP
      kinase cascade. The data identify WSC-1 and HAM-7 as the major cell wall sensors
      that regulate two distinct MAK-1-dependent cellular activities, cell wall
      integrity and hyphal anastomosis, respectively.

PMID- 22879954
TI  - Biotin IgM antibodies in human blood: a previously unknown factor eliciting false
      results in biotinylation-based immunoassays.
AB  - Biotin is an essential vitamin that binds streptavidin or avidin with high
      affinity and specificity. As biotin is a small molecule that can be linked to
      proteins without affecting their biological activity, biotinylation is applied
      widely in biochemical assays. In our laboratory, IgM enzyme immuno assays (EIAs)
      of u-capture format have been set up against many viruses, using as antigen
      biotinylated virus like particles (VLPs) detected by horseradish peroxidase
      conjugated streptavidin. We recently encountered one serum sample reacting with
      the biotinylated VLP but not with the unbiotinylated one, suggesting in human
      sera the occurrence of biotin-reactive antibodies. In the present study, we
      search the general population (612 serum samples from adults and 678 from
      children) for IgM antibodies reactive with biotin and develop an indirect EIA for
      quantification of their levels and assessment of their seroprevalence. These IgM
      antibodies were present in 3% adults regardless of age, but were rarely found in
      children. The adverse effects of the biotin IgM on biotinylation-based
      immunoassays were assessed, including four inhouse and one commercial virus IgM
      EIAs, showing that biotin IgM do cause false positivities. The biotin can not
      bind IgM and streptavidin or avidin simultaneously, suggesting that these biotin
      interactive compounds compete for the common binding site. In competitive
      inhibition assays, the affinities of biotin IgM antibodies ranged from 2.1 * 10(
      3) to 1.7 * 10(-4 )mol/L. This is the first report on biotin antibodies found in
      humans, providing new information on biotinylation-based immunoassays as well as
      new insights into the biomedical effects of vitamins.

PMID- 22879953
TI  - Regulation of DNA replication timing on human chromosome by a cell-type specific
      DNA binding protein SATB1.
AB  - BACKGROUND: Replication timing of metazoan DNA during S-phase may be determined
      by many factors including chromosome structures, nuclear positioning, patterns of
      histone modifications, and transcriptional activity. It may be determined by Mb
      domain structures, termed as "replication domains", and recent findings indicate
      that replication timing is under developmental and cell type-specific regulation.
      METHODOLOGY/PRINCIPAL FINDINGS: We examined replication timing on the human
      5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent
      methods to determine replication timing. One is quantification of nascent
      replicating DNA in cell cycle-fractionated stage-specific S phase populations.
      The other is FISH analyses of replication foci. Although the locations of early-
      and late-replicating domains were common between the two cell lines, the timing
      transition region (TTR) between early and late domains were offset by 200-kb. We
      show that Special AT-rich sequence Binding protein 1 (SATB1), specifically
      expressed in T-cells, binds to the early domain immediately adjacent to TTR and
      delays the replication timing of the TTR. Measurement of the chromosome copy
      number along the TTR during synchronized S phase suggests that the fork movement
      may be slowed down by SATB1. CONCLUSIONS: Our results reveal a novel role of
      SATB1 in cell type-specific regulation of replication timing along the
      chromosome.

PMID- 22879955
TI  - LncRNAs expression signatures of renal clear cell carcinoma revealed by
      microarray.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of pervasive
      genes involved in a variety of biological functions. They are aberrantly
      expressed in many types of cancers. In this study, we described lncRNAs profiles
      in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding
      adjacent nontumorous tissues (NT) by microarray. METHODOLOGY/PRINCIPAL FINDINGS:
      With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the
      number of lncRNAs that expressed at a certain level could be detected is 17157.
      From the data we found there were thousands of lncRNAs that differentially
      expressed (>= 2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs
      differentially expressed in five or more of six RCCC samples. Compared with NT,
      many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data
      showed that down-regulated lncRNAs were more common than up-regulated ones.
      ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty
      three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in
      RCCC compared with matched histologically normal renal tissues.
      CONCLUSIONS/SIGNIFICANCE: Our study is the first one to determine genome-wide
      lncRNAs expression patterns in RCCC by microarray. The results displayed that
      clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples,
      which revealed that lncRNAs differentially expressed in tumor tissues and normal
      tissues may exert a partial or key role in tumor development. Taken together,
      this study may provide potential targets for future treatment of RCCC and novel
      insights into cancer biology.

PMID- 22879956
TI  - Translation inhibitors induce formation of cholesterol ester-rich lipid droplets.
AB  - Lipid droplets (LDs) in non-adipocytes contain triglycerides (TG) and cholesterol
      esters (CE) in variable ratios. TG-rich LDs are generated when unsaturated fatty
      acids are administered, but the conditions that induce CE-rich LD formation are
      less well characterized. In the present study, we found that protein translation
      inhibitors such as cycloheximide (CHX) induced generation of CE-rich LDs and that
      TIP47 (perilipin 3) was recruited to the LDs, although the expression of this
      protein was reduced drastically. Electron microscopy revealed that LDs formed in
      CHX-treated cells possess a distinct electron-dense rim that is not found in TG
      rich LDs, whose formation is induced by oleic acid. CHX treatment caused
      upregulation of mTORC1, but the CHX-induced increase in CE-rich LDs occurred even
      when rapamycin or Torin1 was given along with CHX. Moreover, the increase in CE
      was seen in both wild-type and autophagy-deficient Atg5-null mouse embryonic
      fibroblasts, indicating that mTORC1 activation and suppression of autophagy are
      not necessary to induce the observed phenomenon. The results showed that
      translation inhibitors cause a significant change in the lipid ester composition
      of LDs by a mechanism independent of mTORC1 signaling and autophagy.

PMID- 22879958
TI  - Selfish spermatogonial selection: evidence from an immunohistochemical screen in
      testes of elderly men.
AB  - The dominant congenital disorders Apert syndrome, achondroplasia and multiple
      endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and
      RET proteins respectively-represent classical examples of paternal age-effect
      mutation, a class that arises at particularly high frequencies in the sperm of
      older men. Previous analyses of DNA from randomly selected cadaveric testes
      showed that the levels of the corresponding FGFR2, FGFR3 and RET mutations
      exhibit very uneven spatial distributions, with localised hotspots surrounded by
      large mutation-negative areas. These studies imply that normal testes are mosaic
      for clusters of mutant cells: these clusters are predicted to have altered growth
      and signalling properties leading to their clonal expansion (selfish
      spermatogonial selection), but DNA extraction eliminates the possibility to study
      such processes at a tissue level. Using a panel of antibodies optimised for the
      detection of spermatocytic seminoma, a rare tumour of spermatogonial origin, we
      demonstrate that putative clonal events are frequent within normal testes of
      elderly men (mean age: 73.3 yrs) and can be classed into two broad categories. We
      found numerous small (less than 200 cells) cellular aggregations with distinct
      immunohistochemical characteristics, localised to a portion of the seminiferous
      tubule, which are of uncertain significance. However more infrequently we
      identified additional regions where entire seminiferous tubules had a
      circumferentially altered immunohistochemical appearance that extended through
      multiple serial sections that were physically contiguous (up to 1 mm in length),
      and exhibited enhanced staining for antibodies both to FGFR3 and a marker of
      downstream signal activation, pAKT. These findings support the concept that
      populations of spermatogonia in individual seminiferous tubules in the testes of
      older men are clonal mosaics with regard to their signalling properties and
      activation, thus fulfilling one of the specific predictions of selfish
      spermatogonial selection.

PMID- 22879960
TI  - Predicting the benefits of banana bunchy top virus exclusion from commercial
      plantations in Australia.
AB  - Benefit cost analysis is a tried and tested analytical framework that can clearly
      communicate likely net changes in producer welfare from investment decisions to
      diverse stakeholder audiences. However, in a plant biosecurity context, it is
      often difficult to predict policy benefits over time due to complex biophysical
      interactions between invasive species, their hosts, and the environment. In this
      paper, we demonstrate how a break-even style benefit cost analysis remains highly
      relevant to biosecurity decision-makers using the example of banana bunchy top
      virus, a plant pathogen targeted for eradication from banana growing regions of
      Australia. We develop an analytical approach using a stratified diffusion spread
      model to simulate the likely benefits of exclusion of this virus from commercial
      banana plantations over time relative to a nil management scenario in which no
      surveillance or containment activities take place. Using Monte Carlo simulation
      to generate a range of possible future incursion scenarios, we predict the
      exclusion benefits of the disease will avoid Aus$15.9-27.0 million in annual
      losses for the banana industry. For these exclusion benefits to be reduced to
      zero would require a bunchy top re-establishment event in commercial banana
      plantations three years in every four. Sensitivity analysis indicates that
      exclusion benefits can be greatly enhanced through improvements in disease
      surveillance and incursion response.

PMID- 22879959
TI  - Association of OPA1 polymorphisms with NTG and HTG: a meta-analysis.
AB  - BACKGROUND: Genetic polymorphisms of the Optic atrophy 1 gene have been
      implicated in altering the risk of primary open angle glaucoma (POAG), especially
      the susceptibility to normal tension glaucoma (NTG), but the results remain
      controversial. METHODS: Multiple electronic databases (up to January 20, 2012)
      were searched independently by two investigators. A meta-analysis was performed
      on the association between Optic atrophy 1 polymorphisms (rs 166850 and rs
      10451941) and normal tension glaucoma (NTG)/high tension glaucoma (HTG). Summary
      odds ratios (ORs) and 95% confidence intervals (CI) were estimated. RESULTS:
      Seven studies of 713 cases and 964 controls for NTG and five studies of 1200
      cases and 971 controls for HTG on IVS8+4C>T (rs 166850) and IVS8+32T>C
      (rs10451941) were identified. There were significant associations between the
      OPA1 rs10451941polymorphism and NTG susceptibility for all genetic models(C vs. T
      OR = 1.26, 95% CI 1.09-1.47, p = 0.002; CC vs. TT: OR = 1.52, 95% CI 1.04-2.20, p
      = 0.029; CC vs. CT+TT: OR = 1.64, 95% CI 1.16-2.33, p = 0.005; CC+CT vs. TT: OR =
      1.21, 95% CI 1.02-1.44, p = 0.032). However, no evidence of associations was
      detected between the OPA1 IVS8+32C>T polymorphism and POAG susceptibility to HTG.
      Similarly, clear associations between the rs 166850 variant and NTG were observed
      in allelic and dominant models (T vs. C OR = 1.52, 95% CI 1.16-1.99, p = 0.002;
      TT+TC vs. CC OR = 1.50, 95% CI 1.13-2.01, p = 0.006) but not to HTG. In subgroup
      analyses by ethnicity, we detected an association between both OPA1 polymorphisms
      and risk for NTG in Caucasians but not in Asians. By contrast, no significant
      findings were noted between OPA1 variants for HTG, either in Caucasians or in
      Asians. CONCLUSIONS: Both the IVS8+4C>T and IVS8+32T>C variants may affect
      individual susceptibility to NTG. Moreover, stratified analyses for NTG detecting
      the effects of both OPA1 polymorphisms seemed to vary with ethnicity. Further
      investigations are needed to validate the association.

PMID- 22879961
TI  - Inhibitory effect on in vitro Streptococcus oralis biofilm of a soda-lime glass
      containing silver nanoparticles coating on titanium alloy.
AB  - This paper reports the effect of soda-lime-glass-nAg coating on the viability of
      an in vitro biofilm of Streptococcus oralis. Three strains (ATCC 35037 and two
      clinical isolates from periodontitis patients) were grown on coated with glass,
      glass containing silver nanoparticles, and uncoated titanium alloy disks. Two
      different methods were used to quantify biofilm formation abilities: crystal
      violet staining and determination of viable counts. The influence of the surface
      morphology on the cell attachment was studied. The surface morphology was
      characterized by scanning electron microscopy (SEM) and using a profilometer. SEM
      was also used to study the formation and the development of biofilm on the coated
      and uncoated disks. At least a >99.7% inocula reduction of biofilm respect to
      titanium disks and also to glass coated disks was observed in the glass-nAg
      coated disks for all the studied strains. A quantitative evaluation of the
      release of silver was conducted in vitro to test whether and to what extend the
      biocidal agent (silver) could leach from the coating. These findings suggest that
      the biofilm formation of S. oralis strains is highly inhibited by the glass-nAg
      and may be useful for materials which require durable antibacterial effect on
      their surfaces, as it is the case of dental implants.

PMID- 22879957
TI  - Comparison of 6q25 breast cancer hits from Asian and European Genome Wide
      Association Studies in the Breast Cancer Association Consortium (BCAC).
AB  - The 6q25.1 locus was first identified via a genome-wide association study (GWAS)
      in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210,
      approximately 180 Kb upstream of ESR1. There have been conflicting reports about
      the association of this locus with breast cancer in Europeans, and a GWAS in
      Europeans identified a different SNP, tagged here by rs12662670. We examined the
      associations of both SNPs in up to 61,689 cases and 58,822 controls from forty
      four studies collaborating in the Breast Cancer Association Consortium, of which
      four studies were of Asian and 39 of European descent. Logistic regression was
      used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only
      analyses were used to compare SNP effects in Estrogen Receptor positive (ER+)
      versus negative (ER-) tumours. Models including both SNPs were fitted to
      investigate whether the SNP effects were independent. Both SNPs are significantly
      associated with breast cancer risk in both ethnic groups. Per-allele ORs are
      higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26
      1.48), p = 7.6 * 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 * 10(-18)
      in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 * 10(-9) in
      Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 * 10(-9) in Europeans]. SNP rs2046210
      is associated with a significantly greater risk of ER- than ER+ tumours in
      Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 * 10(-17) versus OR (ER+)
      = 1.07 (95% CI 1.04-1.1), p = 1.3 * 10(-7), p(heterogeneity) = 5.1 * 10(-6)]. In
      these Asian studies, by contrast, there is no clear evidence of a differential
      association by tumour receptor status. Each SNP is associated with risk after
      adjustment for the other SNP. These results suggest the presence of two variants
      at 6q25.1 each independently associated with breast cancer risk in Asians and in
      Europeans. Of these two, the one tagged by rs2046210 is associated with a greater
      risk of ER- tumours.

PMID- 22879962
TI  - Metabolic parameters and emotionality are little affected in G-protein coupled
      receptor 12 (Gpr12) mutant mice.
AB  - BACKGROUND: G-protein coupled receptors (GPR) bear the potential to serve as yet
      unidentified drug targets for psychiatric and metabolic disorders. GPR12 is of
      major interest given its putative role in metabolic function and its unique brain
      distribution, which suggests a role in emotionality and affect. We tested Gpr12
      deficient mice in a series of metabolic and behavioural tests and subjected them
      to a well-established high-fat diet feeding protocol. METHODOLOGY/PRINCIPAL
      FINDINGS: Comparing the mutant mice with wild type littermates, no significant
      differences were seen in body weight, fatness or weight gain induced by a high
      fat diet. The Gpr12 mutant mice displayed a modest but significant lowering of
      energy expenditure and a trend to lower food intake on a chow diet, but no other
      metabolic parameters, including respiratory rate, were altered. No emotionality
      related behaviours (assessed by light-dark box, tail suspension, and open field
      tests) were affected by the Gpr12 gene mutation. CONCLUSIONS/SIGNIFICANCE:
      Studying metabolic and emotionality parameters in Gpr12 mutant mice did not
      reveal a major phenotypic impact of the gene mutation. Compared to previous
      results showing a metabolic phenotype in Gpr12 mice with a mixed 129 and C57Bl6
      background, we suggest that a more pure C57Bl/6 background due to further
      backcrossing might have reduced the phenotypic penetrance.

PMID- 22879963
TI  - Rhodococcus equi's extreme resistance to hydrogen peroxide is mainly conferred by
      one of its four catalase genes.
AB  - Rhodococcus equi is one of the most widespread causes of disease in foals aged
      from 1 to 6 months. R. equi possesses antioxidant defense mechanisms to protect
      it from reactive oxygen metabolites such as hydrogen peroxide (H(2)O(2))
      generated during the respiratory burst of phagocytic cells. These defense
      mechanisms include enzymes such as catalase, which detoxify hydrogen peroxide.
      Recently, an analysis of the R. equi 103 genome sequence revealed the presence of
      four potential catalase genes. We first constructed DeltakatA-, DeltakatB-,
      DeltakatC-and DeltakatD-deficient mutants to study the ability of R. equi to
      survive exposure to H(2)O(2)in vitro and within mouse peritoneal macrophages.
      Results showed that DeltakatA and, to a lesser extent DeltakatC, were affected by
      80 mM H(2)O(2). Moreover, katA deletion seems to significantly affect the ability
      of R. equi to survive within murine macrophages. We finally investigated the
      expression of the four catalases in response to H(2)O(2) assays with a real time
      PCR technique. Results showed that katA is overexpressed 367.9 times (+/- 122.6)
      in response to exposure to 50 mM of H(2)O(2) added in the stationary phase, and
      3.11 times (+/- 0.59) when treatment was administered in the exponential phase.
      In untreated bacteria, katB, katC and katD were overexpressed from 4.3 to 17.5
      times in the stationary compared to the exponential phase. Taken together, our
      results show that KatA is the major catalase involved in the extreme H(2)O(2)
      resistance capability of R. equi.

PMID- 22879964
TI  - The influence of serotonin on fear learning.
AB  - Learning of associations between aversive stimuli and predictive cues is the
      basis of Pavlovian fear conditioning and is driven by a mismatch between
      expectation and outcome. To investigate whether serotonin modulates the formation
      of such aversive cue-outcome associations, we used functional magnetic resonance
      imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT)
      levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT
      depleted subjects compared to a non-depleted control group exhibited attenuated
      autonomic responses to cues indicating the upcoming of an aversive event. These
      results were closely paralleled by reduced aversive learning signals in the
      amygdala and the orbitofrontal cortex, two prominent structures of the neural
      fear circuit. In agreement with current theories of serotonin as a motivational
      opponent system to dopamine in fear learning, our data provide first empirical
      evidence for a role of serotonin in representing formally derived learning
      signals for aversive events.

PMID- 22879965
TI  - Increased cardiovascular and renal risk is associated with low nephron endowment
      in aged females: an ovine model of fetal unilateral nephrectomy.
AB  - Previously we have shown that ovariectomised (OVX) female sheep have reduced
      renal function and elevated blood pressure from 6 months of age following fetal
      uninephrectomy (uni-x) at 100 days of gestation (term = 150 days). In the current
      study we examined if in intact female sheep the onset of decline in renal
      function and elevation in blood pressure was prevented. Studies were performed at
      1 year, 2 and 5 years of age. Following fetal uni-x at 100 days, intact female
      sheep had ~30% reduction in glomerular filtration rate (GFR) at 1 year, which did
      not exacerbate with age (P(treatment) = 0.0001, P(age) = 0.7). In contrast renal
      blood flow was similar between the treatment groups at 1 year of age but had
      declined in the uni-x animals at 5 years of age (P(treatment * age) = 0.046).
      Interestingly, intact uni-x sheep did not develop elevations in arterial pressure
      until 2 years of age. Furthermore, uni-x animals had a similar capacity to
      respond to a cardiac challenge at 1 year and 2 years of age, however, cardiac
      functional reserve was significantly reduced compared to sham group at 5 years of
      age. Uni-x animals exhibited an increase in left ventricular dimensions at 5
      years of age compared to the sham animals and compared to 2 years of age
      (P(treatment)<0.001, P(treatment * age)<0.001). In conclusion, the onset of renal
      dysfunction preceded the onset of hypertension in intact female uni-x sheep.
      Furthermore, this study showed that the intact females are protected from the
      impact of a reduced nephron endowment on cardiovascular health early in life as
      opposed to our findings in young male sheep and OVX uni-x female sheep. However,
      with ageing this protection is lost as evidenced by presence of left ventricular
      hypertrophy and impaired cardiac function in 5 year old uni-x female sheep.

PMID- 22879966
TI  - Systematic testing of literature reported genetic variation associated with
      coronary restenosis: results of the GENDER Study.
AB  - BACKGROUND: Coronary restenosis after percutaneous coronary intervention still
      remains a significant problem, despite all medical advances. Unraveling the
      mechanisms leading to restenosis development remains challenging. Many studies
      have identified genetic markers associated with restenosis, but consistent
      replication of the reported markers is scarce. The aim of the current study was
      to analyze the joined effect of previously in literature reported candidate genes
      for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.
      METHODOLOGY/PRINCIPAL FINDINGS: Candidate genes were selected using a MEDLINE
      search including the terms 'genetic polymorphism' and 'coronary restenosis'. The
      final set included 36 genes. Subsequently, all single nucleotide polymorphisms
      (SNPs) in the genomic region of these genes were analyzed in GENDER using set
      based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586
      SNPs of 295 cases with restenosis and 571 matched controls. The set, including
      all 36 literature reported genes, was, indeed, significantly associated with
      restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual
      genes demonstrated that the observed association of the complete set was
      determined by 6 of the 36 genes. CONCLUSION: Despite overt inconsistencies in
      literature, with regard to individual candidate gene studies, this is the first
      study demonstrating that the joint effect of all these genes together, indeed, is
      associated with restenosis.

PMID- 22879967
TI  - Production of a subunit vaccine candidate against porcine post-weaning diarrhea
      in high-biomass transplastomic tobacco.
AB  - Post-weaning diarrhea (PWD) in piglets is a major problem in piggeries worldwide
      and results in severe economic losses. Infection with Enterotoxigenic Escherichia
      coli (ETEC) is the key culprit for the PWD disease. F4 fimbriae of ETEC are
      highly stable proteinaceous polymers, mainly composed of the major structural
      subunit FaeG, with a capacity to evoke mucosal immune responses, thus
      demonstrating a potential to act as an oral vaccine against ETEC-induced porcine
      PWD. In this study we used a transplastomic approach in tobacco to produce a
      recombinant variant of the FaeG protein, rFaeG(ntd/dsc), engineered for
      expression as a stable monomer by N-terminal deletion and donor strand
      complementation (ntd/dsc). The generated transplastomic tobacco plants
      accumulated up to 2.0 g rFaeG(ntd/dsc) per 1 kg fresh leaf tissue (more than 1%
      of dry leaf tissue) and showed normal phenotype indistinguishable from wild type
      untransformed plants. We determined that chloroplast-produced rFaeG(ntd/dsc)
      protein retained the key properties of an oral vaccine, i.e. binding to porcine
      intestinal F4 receptors (F4R), and inhibition of the F4-possessing (F4+) ETEC
      attachment to F4R. Additionally, the plant biomass matrix was shown to delay
      degradation of the chloroplast-produced rFaeG(ntd/dsc) in gastrointestinal
      conditions, demonstrating a potential to function as a shelter-vehicle for
      vaccine delivery. These results suggest that transplastomic plants expressing the
      rFaeG(ntd/dsc) protein could be used for production and, possibly, delivery of an
      oral vaccine against porcine F4+ ETEC infections. Our findings therefore present
      a feasible approach for developing an oral vaccination strategy against porcine
      PWD.

PMID- 22879968
TI  - Association of Caucasian-identified variants with colorectal cancer risk in
      Singapore Chinese.
AB  - BACKGROUND: Genome-wide association studies (GWAS) in Caucasians have identified
      fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal
      cancer (CRC) risk. METHODS: We investigated the role of eleven iSNPs or surrogate
      SNPs (sSNPs), in high linkage disequilibrium (LD, r(2)>= 0.8) and within 100 kb
      vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH) cases
      and controls. RESULTS: Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584,
      rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1
      and 18q21.1 respectively showed evidence of association with CRC risk, with odds
      ratios (OR) ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with
      rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88) but not disease prognosis (OR =
      0.91, 95% CI 0.69-1.20). Interestingly, sSNP rs3087967 at 11q23.1 was associated
      with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58) but not women (OR = 1.07, 95%
      CI: 0.88-1.29), suggesting a gender-specific role. Half of the Caucasian
      identified variants, including the recently fine-mapped BMP pathway loci, BMP4,
      GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH
      (OR ~1; p-value >0.1). Comparing the results of this study with that of the
      Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14,
      11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese
      studies. CONCLUSIONS: The contrasting results between Caucasians and Chinese
      could be due to different LD patterns and allelic frequencies or genetic
      heterogeneity. The results suggest that additional common variants contributing
      to CRC predisposition remained to be identified.

PMID- 22879969
TI  - Knocking out ACR2 does not affect arsenic redox status in Arabidopsis thaliana:
      implications for as detoxification and accumulation in plants.
AB  - Many plant species are able to reduce arsenate to arsenite efficiently, which is
      an important step allowing detoxification of As through either efflux of arsenite
      or complexation with thiol compounds. It has been suggested that this reduction
      is catalyzed by ACR2, a plant homologue of the yeast arsenate reductase ScACR2.
      Silencing of AtACR2 was reported to result in As hyperaccumulation in the shoots
      of Arabidopsis thaliana. However, no information of the in vivo As speciation has
      been reported. Here, we investigated the effect of AtACR2 knockout or
      overexpression on As speciation, arsenite efflux from roots and As accumulation
      in shoots. T-DNA insertion lines, overexpression lines and wild-type (WT) plants
      were exposed to different concentrations of arsenate for different periods, and
      As speciation in plants and arsenite efflux were determined using HPLC-ICP-MS.
      There were no significant differences in As speciation between different lines,
      with arsenite accounting for >90% of the total extractable As in both roots and
      shoots. Arsenite efflux to the external medium represented on average 77% of the
      arsenate taken up during 6 h exposure, but there were no significant differences
      between WT and mutants or overexpression lines. Accumulation of As in the shoots
      was also unaffected by AtACR2 knockout or overexpression. Additionally, after
      exposure to arsenate, the yeast (Saccharomyces cerevisiae) strain with ScACR2
      deleted showed similar As speciation as the WT with arsenite-thiol complexes
      being the predominant species. Our results suggest the existence of multiple
      pathways of arsenate reduction in plants and yeast.

PMID- 22879970
TI  - Predicting human age with bloodstains by sjTREC quantification.
AB  - The age-related decline of signal joint T-cell receptor rearrangement excision
      circles (sjTRECs) in human peripheral blood has been demonstrated in our previous
      study and other reports. Until now, only a few studies on sjTREC detection in
      bloodstain samples were reported, which were based on a small sample of subjects
      of a limited age range, although bloodstains are much more frequently encountered
      in forensic practice. In this present study, we adopted the sensitive Taqman real
      time quantitative polymerase chain reaction (qPCR) method to perform sjTREC
      quantification in bloodstains from individuals ranging from 0-86 years old (n =
      264). The results revealed that sjTREC contents in human bloodstains were
      declined in an age-dependent manner (r = -0.8712). The formula of age estimation
      was Age = -7.1815Y-42.458 +/- 9.42 (Y dCt(TBP-sjTREC); 9.42 standard error).
      Furthermore, we tested for the influence of short- or long- storage time by
      analyzing fresh and stored bloodstains from the same individuals. Remarkably, no
      statistically significant difference in sjTREC contents was found between the
      fresh and old DNA samples over a 4-week of storage time. However, significant
      loss (0.16-1.93 dCt) in sjTREC contents was detected after 1.5 years of storage
      in 31 samples. Moreover, preliminary sjTREC quantification from up to 20-year-old
      bloodstains showed that though the sjTREC contents were detectable in all samples
      and highly correlated with donor age, a time-dependent decrease in the
      correlation coefficient r was found, suggesting the predicting accuracy of this
      described assay would be deteriorated in aged samples. Our findings show that
      sjTREC quantification might be also suitable for age prediction in bloodstains,
      and future researches into the time-dependent or other potential impacts on
      sjTREC quantification might allow further improvement of the predicting accuracy.

PMID- 22879971
TI  - SPARC is a key regulator of proliferation, apoptosis and invasion in human
      ovarian cancer.
AB  - BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), a calcium
      binding matricellular glycoprotein, is implicated in the progression of many
      cancers. In this study, we investigated the expression and function of SPARC in
      ovarian cancer. METHODS: cDNA microarray analysis was performed to compare gene
      expression profiles of the highly invasive and the low invasive subclones derived
      from the SKOV3 human ovarian cancer cell line. Immunohistochemistry (IHC)
      staining was performed to investigate SPARC expression in a total of 140 ovarian
      tissue specimens. In functional assays, effects of SPARC knockdown on the
      biological behavior of ovarian cancer cells were investigated. The mechanisms of
      SPARC in ovarian cancer proliferation, apoptosis and invasion were also
      researched. RESULTS: SPARC was overexpressed in the highly invasive subclone
      compared with the low invasive subclone. High SPARC expression was associated
      with high stage, low differentiation, lymph node metastasis and poor prognosis of
      ovarian cancer. Knockdown of SPARC expression significantly suppressed ovarian
      cancer cell proliferation, induced cell apoptosis and inhibited cell invasion and
      metastasis. CONCLUSION: SPARC is overexpressed in highly invasive subclone and
      ovarian cancer tissues and plays an important role in ovarian cancer growth,
      apoptosis and metastasis.

PMID- 22879972
TI  - Emergency department use by released prisoners with HIV: an observational
      longitudinal study.
AB  - BACKGROUND: Many people living with HIV access healthcare systems through the
      emergency department (ED), and increased ED use may be indicative of
      disenfranchisement with primary HIV care, under-managed comorbid disease, or
      coincide with use of other healthcare resources. The goal of this study was to
      investigate ED use by HIV-infected prisoners transitioning to communities.
      METHODS: We evaluated ED use by 151 HIV-infected released prisoners who were
      enrolled in a randomized controlled trial of directly administered versus self
      administered antiretroviral therapy in Connecticut. Primary outcomes were
      quantity and type of ED visits and correlates of ED use were evaluated with
      multivariate models by Poisson regression. RESULTS: In the 12 months post
      release, there were 227 unique ED contacts made by 85/151 (56%) subjects. ED
      visits were primarily for acute febrile syndromes (32.6%) or pain (20.3%),
      followed by substance use issues (19.4%), trauma (18%), mental illness (11%), and
      social access issues (4.4%). Compared to those not utilizing the ED, users were
      more likely to be white, older, and unmarried, with less trust in their physician
      and poorer perceived physical health but greater social support. In multivariate
      models, ED use was correlated with moderate to severe depression (IRR = 1.80),
      being temporarily housed (IRR = 0.54), and alcohol addiction severity (IRR =
      0.21) but not any surrogates of HIV severity. CONCLUSIONS: EDs are frequent
      sources of care after prison-release with visits often reflective of social and
      psychiatric instability. Future interventions should attempt to fill resource
      gaps, engage released prisoners in continuous HIV care, and address these
      substantial needs.

PMID- 22879973
TI  - Characterization of a human 12/15-lipoxygenase promoter variant associated with
      atherosclerosis identifies vimentin as a promoter binding protein.
AB  - BACKGROUND: Sequence variation in the human 12/15 lipoxygenase (ALOX15) has been
      associated with atherosclerotic disease. We functionally characterized an ALOX15
      promoter polymorphism, rs2255888, previously associated with carotid plaque
      burden. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate specific in vitro and in
      vivo binding of the cytoskeletal protein, vimentin, to the ALOX15 promoter. We
      show that the two promoter haplotypes carrying alternate alleles at rs2255888
      exhibit significant differences in promoter activity by luciferase reporter assay
      in two cell lines. Differences in in-vitro vimentin-binding to and formation of
      DNA secondary structures in the polymorphic promoter sequence are also detected
      by electrophoretic mobility shift assay and biophysical analysis, respectively.
      We show regulation of ALOX15 protein by vimentin. CONCLUSIONS/SIGNIFICANCE: This
      study suggests that vimentin binds the ALOX15 promoter and regulates its promoter
      activity and protein expression. Sequence variation that results in changes in
      DNA conformation and vimentin binding to the promoter may be relevant to ALOX15
      gene regulation.

PMID- 22879974
TI  - Laninamivir octanoate and artificial surfactant combination therapy significantly
      increases survival of mice infected with lethal influenza H1N1 Virus.
AB  - BACKGROUND: Patients with influenza virus infection can develop severe pneumonia
      and acute respiratory distress syndrome (ARDS) which have a high mortality.
      Influenza virus infection is treated worldwide mainly by neuraminidase inhibitors
      (NAIs). However, monotherapy with NAIs is insufficient for severe pneumonia
      secondary to influenza virus infection. We previously demonstrated that mice
      infected with a lethal dose of influenza virus develop diffuse alveolar damage
      (DAD) with alveolar collapse similar to that seen in ARDS in humans.
      Additionally, pulmonary surfactant proteins were gradually increased in mouse
      serum, suggesting a decrease in pulmonary surfactant in the lung. Therefore, the
      present study examined whether combination therapy of NAI with exogenous
      artificial surfactant affects mortality of influenza virus-infected mice.
      METHODOLOGY/PRINCIPAL FINDINGS: BALB/c mice were inoculated with several viral
      doses of influenza A/Puerto Rico/8/34 (PR8) virus (H1N1). The mice were
      additionally administered exogenous artificial surfactant in the presence or
      absence of a new NAI, laninamivir octanoate. Mouse survival, body weight and
      general condition were observed for up to 20 days after inoculation. Viral titer
      and cytokine/chemokine levels in the lungs, lung weight, pathological analysis,
      and blood O(2) and CO(2) pressures were evaluated. Infected mice treated with
      combination therapy of laninamivir octanoate with artificial surfactant showed a
      significantly higher survival rate compared with those that received laninamivir
      octanoate monotherapy (p = 0.003). However, virus titer, lung weight and
      cytokine/chemokine responses were not different between the groups.
      Histopathological examination, a hydrostatic lung test and blood gas analysis
      showed positive results in the combination therapy group.
      CONCLUSIONS/SIGNIFICANCE: Combination therapy of laninamivir octanoate with
      artificial surfactant reduces lethality in mice infected with influenza virus,
      and eventually suppresses DAD formation and preserves lung function. This
      combination could be effective for prevention of severe pneumonia secondary to
      influenza virus infection in humans, which is not improved by NAI monotherapy.

PMID- 22879975
TI  - Blood cell mitochondrial DNA content and premature ovarian aging.
AB  - Primary ovarian insufficiency (POI) is a critical fertility defect characterized
      by an anticipated and silent impairment of the follicular reserve, but its
      pathogenesis is largely unexplained. The frequent maternal inheritance of POI
      together with a remarkable dependence of ovarian folliculogenesis upon
      mitochondrial biogenesis and bioenergetics suggested the possible involvement of
      a generalized mitochondrial defect. Here, we verified the existence of a
      significant correlation between blood and ovarian mitochondrial DNA (mtDNA)
      content in a group of women undergoing ovarian hyperstimulation (OH), and then
      aimed to verify whether mtDNA content was significantly altered in the blood
      cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59
      women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A
      Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both
      POF and PR women in comparison with 43 women of similar age and intact ovarian
      reserve, or 53 very old women with a previous physiological menopause. No
      pathogenic variations in the mitochondrial DNA polymerase gamma (POLG) gene were
      detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood
      cell mtDNA depletion is a frequent finding among women with premature ovarian
      aging, suggesting that a still undetermined but generalized mitochondrial defect
      may frequently predispose to POI which could then be considered a form of
      anticipated aging in which the ovarian defect may represent the first
      manifestation. The determination of mtDNA content in blood may become an useful
      tool for the POI risk prediction.

PMID- 22879976
TI  - Functional and molecular characterization of the role of CTCF in human embryonic
      stem cell biology.
AB  - The CCCTC-binding factor CTCF is the only known vertebrate insulator protein and
      has been shown to regulate important developmental processes such as imprinting,
      X-chromosome inactivation and genomic architecture. In this study, we examined
      the role of CTCF in human embryonic stem cell (hESC) biology. We demonstrate that
      CTCF associates with several important pluripotency genes, including NANOG, SOX2,
      cMYC and LIN28 and is critical for hESC proliferation. CTCF depletion impacts
      expression of pluripotency genes and accelerates loss of pluripotency upon BMP4
      induced differentiation, but does not result in spontaneous differentiation. We
      find that CTCF associates with the distal ends and internal sites of the co
      regulated 160 kb NANOG-DPPA3-GDF3 locus. Each of these sites can function as a
      CTCF-dependent enhancer-blocking insulator in heterologous assays. In hESCs, CTCF
      exists in multisubunit protein complexes and can be poly(ADP)ribosylated. Known
      CTCF cofactors, such as Cohesin, differentially co-localize in the vicinity of
      specific CTCF binding sites within the NANOG locus. Importantly, the association
      of some cofactors and protein PARlation selectively changes upon differentiation
      although CTCF binding remains constant. Understanding how unique cofactors may
      impart specialized functions to CTCF at specific genomic locations will further
      illuminate its role in stem cell biology.

PMID- 22879977
TI  - A novel mutation in beta integrin reveals an integrin-mediated interaction
      between the extracellular matrix and cki-1/p27KIP1.
AB  - The cell-extracellular matrix (ECM) interaction plays an essential role in
      maintaining tissue shapes and regulates cell behaviors such as cell adhesion,
      differentiation and proliferation. The mechanism by which the ECM influences the
      cell cycle in vivo is poorly understood. Here we demonstrate that the beta
      integrin PAT-3 regulates the localization and expression of CKI-1, a C. elegans
      homologue of the cyclin dependent kinase inhibitor p27(KIP1). In nematodes
      expressing wild type PAT-3, CKI-1::GFP localizes primarily to nucleoli in
      hypodermal cells, whereas in animals expressing mutant pat-3 with a defective
      splice junction, CKI-1::GFP appears clumped and disorganized in nucleoplasm. RNAi
      analysis links cell adhesion genes to the regulation of CKI-1. RNAi of unc
      52/perlecan, ina-1/alpha integrin, pat-4/ILK, and unc-97/PINCH resulted in
      abnormal CKI-1::GFP localization. Additional RNAi experiments revealed that the
      SCF E3 ubiquitin-ligase complex genes, skpt-1/SKP2, cul-1/CUL1 and lin-23/F-box,
      are required for the proper localization and expression of CKI-1, suggesting that
      integrin signaling and SCF E3 ligase work together to regulate the cellular
      distribution of CKI-1. These data also suggest that integrin plays a major role
      in maintaining proper CKI-1/p27(KIP1) levels in the cell. Perturbed integrin
      signaling may lead to the inhibition of SCF ligase activity, mislocalization and
      elevation of CKI-1/p27(KIP1). These results suggest that adhesion signaling is
      crucial for cell cycle regulation in vivo.

PMID- 22879979
TI  - Heme oxygenase-1 protects retinal endothelial cells against high glucose- and
      oxidative/nitrosative stress-induced toxicity.
AB  - Diabetic retinopathy is a leading cause of visual loss and blindness,
      characterized by microvascular dysfunction. Hyperglycemia is considered the major
      pathogenic factor for the development of diabetic retinopathy and is associated
      with increased oxidative/nitrosative stress in the retina. Since heme oxygenase-1
      (HO-1) is an enzyme with antioxidant and protective properties, we investigated
      the potential protective role of HO-1 in retinal endothelial cells exposed to
      high glucose and oxidative/nitrosative stress conditions. Retinal endothelial
      cells were exposed to elevated glucose, nitric oxide (NO) and hydrogen peroxide
      (H(2)O(2)). Cell viability and apoptosis were assessed by MTT assay, Hoechst
      staining, TUNEL assay and Annexin V labeling. The production of reactive oxygen
      species (ROS) was detected by the oxidation of 2',7'-dichlorodihydrofluorescein
      diacetate. The content of HO-1 was assessed by immunobloting and
      immunofluorescence. HO activity was determined by bilirubin production. Long-term
      exposure (7 days) of retinal endothelial cells to elevated glucose decreased cell
      viability and had no effect on HO-1 content. However, a short-time exposure (24
      h) to elevated glucose did not alter cell viability, but increased both the
      levels of intracellular ROS and HO-1 content. Moreover, the inhibition of HO with
      SnPPIX unmasked the toxic effect of high glucose and revealed the protection
      conferred by HO-1. Oxidative/nitrosative stress conditions increased cell death
      and HO-1 protein levels. These effects of elevated glucose and HO inhibition on
      cell death were confirmed in primary endothelial cells (HUVECs). When cells were
      exposed to oxidative/nitrosative stress conditions there was also an increase in
      retinal endothelial cell death and HO-1 content. The inhibition of HO enhanced
      ROS production and the toxic effect induced by exposure to H(2)O(2) and NOC-18
      (NO donor). Overexpression of HO-1 prevented the toxic effect induced by H(2)O(2)
      and NOC-18. In conclusion, HO-1 exerts a protective effect in retinal endothelial
      cells exposed to hyperglycemic and oxidative/nitrosative stress conditions.

PMID- 22879978
TI  - Enhanced ADCC activity of affinity maturated and Fc-engineered mini-antibodies
      directed against the AML stem cell antigen CD96.
AB  - CD96, a cell surface antigen recently described to be preferentially expressed on
      acute myeloid leukemia (AML) leukemic stem cells (LSC) may represent an
      interesting target structure for the development of antibody-based therapeutic
      approaches. The v-regions from the CD96-specific hybridoma TH-111 were isolated
      and used to generate a CD96-specific single chain fragment of the variable
      regions (scFv). An affinity maturated variant resulting in 4-fold enhanced CD96
      binding was generated by random mutagenesis and stringent selection using phage
      display. The affinity maturated scFv CD96-S32F was used to generate bivalent mini
      antibodies by genetically fusing an IgG1 wild type Fc region or a variant with
      enhanced CD16a binding. Antibody dependent cell-mediated cytotoxicity (ADCC)
      experiments revealed that Fc engineering was essential to trigger significant
      effector cell-mediated lysis when the wild type scFv was used. The mini-antibody
      variant generated by fusing the affinity-maturated scFv with the optimized Fc
      variant demonstrated the highest ADCC activity (2.3-fold enhancement in
      efficacy). In conclusion, our data provide proof of concept that CD96 could serve
      as a target structure for effector cell-mediated lysis and demonstrate that both
      enhancing affinity for CD96 and for CD16a resulted in mini-antibodies with the
      highest cytolytic potential.

PMID- 22879980
TI  - The modular nature of dendritic cell responses to commensal and pathogenic fungi.
AB  - The type of adaptive immune response following host-fungi interaction is largely
      determined at the level of the antigen-presenting cells, and in particular by
      dendritic cells (DCs). The extent to which transcriptional regulatory events
      determine the decision making process in DCs is still an open question. By
      applying the highly structured DC-ATLAS pathways to analyze DC responses, we
      classified the various stimuli by revealing the modular nature of the different
      transcriptional programs governing the recognition of either pathogenic or
      commensal fungi. Through comparison of the network parts affected by DC
      stimulation with fungal cells and purified single agonists, we could determine
      the contribution of each receptor during the recognition process. We observed
      that initial recognition of a fungus creates a temporal window during which the
      simultaneous recruitment of cell surface receptors can intensify, complement and
      sustain the DC activation process. The breakdown of the response to whole live
      cells, through the purified components, showed how the response to invading fungi
      uses a set of specific modules. We find that at the start of fungal recognition,
      DCs rapidly initiate the activation process. Ligand recognition is further
      enhanced by over-expression of the receptor genes, with a significant
      correspondence between gene expression and protein levels and function. Then a
      marked decrease in the receptor levels follows, suggesting that at this moment
      the DC commits to a specific fate. Overall our pathway based studies show that
      the temporal window of the fungal recognition process depends on the availability
      of ligands and is different for pathogens and commensals. Modular analysis of
      receptor and signalling-adaptor expression changes, in the early phase of
      pathogen recognition, is a valuable tool for rapid and efficient dissection of
      the pathogen derived components that determine the phenotype of the DC and
      thereby the type of immune response initiated.

PMID- 22879981
TI  - Seed-based biclustering of gene expression data.
AB  - BACKGROUND: Accumulated biological research outcomes show that biological
      functions do not depend on individual genes, but on complex gene networks.
      Microarray data are widely used to cluster genes according to their expression
      levels across experimental conditions. However, functionally related genes
      generally do not show coherent expression across all conditions since any given
      cellular process is active only under a subset of conditions. Biclustering finds
      gene clusters that have similar expression levels across a subset of conditions.
      This paper proposes a seed-based algorithm that identifies coherent genes in an
      exhaustive, but efficient manner. METHODS: In order to find the biclusters in a
      gene expression dataset, we exhaustively select combinations of genes and
      conditions as seeds to create candidate bicluster tables. The tables have two
      columns (a) a gene set, and (b) the conditions on which the gene set have
      dissimilar expression levels to the seed. First, the genes with less than the
      maximum number of dissimilar conditions are identified and a table of these genes
      is created. Second, the rows that have the same dissimilar conditions are grouped
      together. Third, the table is sorted in ascending order based on the number of
      dissimilar conditions. Finally, beginning with the first row of the table, a test
      is run repeatedly to determine whether the cardinality of the gene set in the row
      is greater than the minimum threshold number of genes in a bicluster. If so, a
      bicluster is outputted and the corresponding row is removed from the table.
      Repeating this process, all biclusters in the table are systematically identified
      until the table becomes empty. CONCLUSIONS: This paper presents a novel
      biclustering algorithm for the identification of additive biclusters. Since it
      involves exhaustively testing combinations of genes and conditions, the additive
      biclusters can be found more readily.

PMID- 22879982
TI  - Structure determination and functional analysis of a chromate reductase from
      Gluconacetobacter hansenii.
AB  - Environmental protection through biological mechanisms that aid in the reductive
      immobilization of toxic metals (e.g., chromate and uranyl) has been identified to
      involve specific NADH-dependent flavoproteins that promote cell viability. To
      understand the enzyme mechanisms responsible for metal reduction, the enzyme
      kinetics of a putative chromate reductase from Gluconacetobacter hansenii (Gh
      ChrR) was measured and the crystal structure of the protein determined at 2.25 A
      resolution. Gh-ChrR catalyzes the NADH-dependent reduction of chromate,
      ferricyanide, and uranyl anions under aerobic conditions. Kinetic measurements
      indicate that NADH acts as a substrate inhibitor; catalysis requires chromate
      binding prior to NADH association. The crystal structure of Gh-ChrR shows the
      protein is a homotetramer with one bound flavin mononucleotide (FMN) per subunit.
      A bound anion is visualized proximal to the FMN at the interface between adjacent
      subunits within a cationic pocket, which is positioned at an optimal distance for
      hydride transfer. Site-directed substitutions of residues proposed to involve in
      both NADH and metal anion binding (N85A or R101A) result in 90-95% reductions in
      enzyme efficiencies for NADH-dependent chromate reduction. In comparison site
      directed substitution of a residue (S118A) participating in the coordination of
      FMN in the active site results in only modest (50%) reductions in catalytic
      efficiencies, consistent with the presence of a multitude of side chains that
      position the FMN in the active site. The proposed proximity relationships between
      metal anion binding site and enzyme cofactors is discussed in terms of rational
      design principles for the use of enzymes in chromate and uranyl bioremediation.

PMID- 22879983
TI  - Patterns of DNA methylation in development, division of labor and hybridization
      in an ant with genetic caste determination.
AB  - BACKGROUND: DNA methylation is a common regulator of gene expression, including
      acting as a regulator of developmental events and behavioral changes in adults.
      Using the unique system of genetic caste determination in Pogonomyrmex barbatus,
      we were able to document changes in DNA methylation during development, and also
      across both ancient and contemporary hybridization events. METHODOLOGY/PRINCIPAL
      FINDINGS: Sodium bisulfite sequencing demonstrated in vivo methylation of
      symmetric CG dinucleotides in P. barbatus. We also found methylation of non-CpG
      sequences. This validated two bioinformatics methods for predicting gene
      methylation, the bias in observed to expected ratio of CpG dinucleotides and the
      density of CpG/TpG single nucleotide polymorphisms (SNP). Frequencies of genomic
      DNA methylation were determined for different developmental stages and castes
      using ms-AFLP assays. The genetic caste determination system (GCD) is probably
      the product of an ancestral hybridization event between P. barbatus and P.
      rugosus. Two lineages obligately co-occur within a GCD population, and queens are
      derived from intra-lineage matings whereas workers are produced from inter
      lineage matings. Relative DNA methylation levels of queens and workers from GCD
      lineages (contemporary hybrids) were not significantly different until adulthood.
      Virgin queens had significantly higher relative levels of DNA methylation
      compared to workers. Worker DNA methylation did not vary among developmental
      stages within each lineage, but was significantly different between the currently
      hybridizing lineages. Finally, workers of the two genetic caste determination
      lineages had half as many methylated cytosines as workers from the putative
      parental species, which have environmental caste determination.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that DNA methylation may be a
      conserved regulatory mechanism moderating division of labor in both bees and
      ants. Current and historic hybridization appear to have altered genomic
      methylation levels suggesting a possible link between changes in overall DNA
      methylation and the origin and regulation of genetic caste determination in P.
      barbatus.

PMID- 22879984
TI  - Evaluation of TcpF-A2-CTB chimera and evidence of additive protective efficacy of
      immunizing with TcpF and CTB in the suckling mouse model of cholera.
AB  - The secreted colonization factor, TcpF, which is produced by Vibrio cholerae 01
      and 0139, has generated interest as a potential protective antigen in the
      development of a subunit vaccine against cholera. This study evaluated
      immunogenicity/protective efficacy of a TcpF holotoxin-like chimera (TcpF-A2-CTB)
      following intraperitoneal immunization compared to TcpF alone, a TcpF+CTB
      mixture, or CTB alone. Immunization with the TcpF-A2-CTB chimera elicited
      significantly greater amounts of anti-TcpF IgG than immunization with the other
      antigens (P<0.05). Protective efficacy was measured using 6-day-old pups reared
      from immunized dams and orogastrically challenged with a lethal dose of El Tor V.
      cholerae 01 Inaba strain N16961. Protection from death, and weight loss analysis
      at 24 and 48 hours post-infection demonstrated that immunization with TcpF alone
      was poorly protective. However, immunization with TcpF+CTB was highly protective
      and showed a trend toward greater protection than immunization with CTB alone
      (82% vs 64% survival). Immunization with the TcpF-A2-CTB chimera demonstrated
      less protection (50% survival) than immunization with the TcpF+CTB mixture. The
      TcpF-A2-CTB chimera used for this study contained the heterologous classical CTB
      variant whereas the El Tor CTB variant (expressed by the challenge strain) was
      used in the other immunization groups. For all immunization groups that received
      CTB, quantitative ELISA data demonstrated that the amounts of serum IgG directed
      against the homologous immunizing CTB antigen was statistically greater than the
      amount to the heterologous CTB antigen (P<=0.003). This finding provides a likely
      explanation for the poorer protection observed following immunization with the
      TcpF-A2-CTB chimera and the relatively high level of protection seen after
      immunization with homologous CTB alone. Though immunization with TcpF alone
      provided no protection, the additive protective effect when TcpF was combined
      with CTB demonstrates its possible value as a component of a multivalent subunit
      vaccine against Vibrio cholerae 01 and 0139.

PMID- 22879985
TI  - Effects of sublethal cadmium exposure on antipredator behavioural and antitoxic
      responses in the invasive amphipod Dikerogammarus villosus.
AB  - Amphipods are recognised as an important component of freshwater ecosystems and
      are frequently used as an ecotoxicological test species. Despite this double
      interest, there is still a lack of information concerning toxic impacts on
      ecologically relevant behaviours. The present study investigated the influence of
      cadmium (Cd), a non-essential heavy metal, on both antipredator behaviours and
      antitoxic responses in the invasive amphipod Dikerogammarus villosus under
      laboratory conditions. Amphipod behaviour (i.e. refuge use, aggregation with
      conspecifics, exploration and mobility) was recorded following a 4-min test
      exposure to 500 ug Cd/L with or without a 24-h Cd pre-exposure and in the
      presence or absence of a high perceived risk of predation (i.e. water scented by
      fish predators and injured conspecifics). Following behavioural tests,
      malondialdehyde (MDA) levels, a biomarker for toxic effect, and energy reserves
      (i.e. lipid and glycogen contents) were assessed. Cd exposures induced (1) cell
      damage reflected by high MDA levels, (2) erratic behaviour quantified by
      decreasing refuge use and exploration, and increasing mobility, and (3) a
      depletion in energy reserves. No significant differences were observed between 4
      min test-exposed and 24-h pre-exposed individuals. Gammarids exposed to Cd had a
      disturbed perception of the alarm stimuli, reflected by increased time spent
      outside of refuges and higher mobility compared to gammarids exposed to
      unpolluted water. Our results suggest that Cd exposure rapidly disrupts the
      normal behavioural responses of gammarids to alarm substances and alters predator
      avoidance strategies, which could have potential impacts on aquatic communities.

PMID- 22879986
TI  - Association of Fcgamma receptor IIB polymorphism with cryptococcal meningitis in
      HIV-uninfected Chinese patients.
AB  - BACKGROUND: As important regulators of the immune system, the human Fcgamma
      receptors (FcgammaRs) have been demonstrated to play important roles in the
      pathogenesis of various infectious diseases. The aim of the present study was to
      identify the association between FCGR polymorphisms and cryptococcal meningitis.
      METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study,
      we genotyped four functional polymorphisms in low-affinity FcgammaRs, including
      FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients
      with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot
      technology. Among the 117 patients with cryptococcal meningitis, 59 had
      predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I
      genotype was over-presented (OR = 1.652, 95% CI [1.02-2.67]; P = 0.039) and the
      FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33-0.90]; P =
      0.016) in comparison with control group. In cryptococcal meningitis patients
      without predisposing factors, FCGR2B 232I/I genotype was also more frequently
      detected (OR = 1.958, 95% CI [1.05-3.66]; P = 0.033), and the FCGR2B 232I/T
      genotype was also less frequently detected (OR = 0.467, 95% CI [0.24-0.91]; P =
      0.023) than in controls. No significant difference was found among FCGR2A 131H/R,
      FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and
      controls. CONCLUSION/SIGNIFICANCE: We found for the first time associations
      between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that
      FcgammaRIIB might play an important role in the central nervous system infection
      by Cryptococcus in HIV-uninfected individuals.

PMID- 22879987
TI  - Probing a polar cluster in the retinal binding pocket of bacteriorhodopsin by a
      chemical design approach.
AB  - Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal
      molecule, which is responsible for light harvesting to fuel proton pumping. From
      our previous studies, we have shown that threonine 90 is the pivotal amino acid
      in this polar cluster, both functionally and structurally. In an attempt to
      perform a phenotype rescue, we have chemically designed a retinal analogue
      molecule to compensate the drastic effects of the T90A mutation in
      bacteriorhodopsin. This analogue substitutes the methyl group at position C(13)
      of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have
      analyzed the effect of reconstituting the wild-type and the T90A mutant
      apoproteins with all-trans-retinal and its 20-methyl derivative (hereafter, 13
      ethyl retinal). Biophysical characterization indicates that recovering the steric
      interaction between the residue 90 and retinal, eases the accommodation of the
      chromophore, however it is not enough for a complete phenotype rescue. The
      characterization of these chemically engineered chromoproteins provides further
      insight into the role of the hydrogen bond network and the steric interactions
      involving the retinal binding pocket in bacteriorhodopsin and other microbial
      sensory rhodopsins.

PMID- 22879988
TI  - Detection of bladder cancer using proteomic profiling of urine sediments.
AB  - We used protein expression profiles to develop a classification rule for the
      detection and prognostic assessment of bladder cancer in voided urine samples.
      Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles
      of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a
      training set of 85 voided urine samples (32 controls and 53 bladder cancer), and
      a blinded testing set of 68 voided urine samples (33 controls and 35 bladder
      cancer). Using t-tests, we identified 473 peaks showing significant differential
      expression across different categories of paired bladder tumor and adjacent
      urothelial samples compared to normal urothelium. Then the intensities of those
      473 peaks were examined in a training set of voided urine samples. Using this
      approach, we identified 41 protein peaks that were differentially expressed in
      both sets of samples. The expression pattern of the 41 protein peaks was used to
      classify the voided urine samples as malignant or benign. This approach yielded a
      sensitivity and specificity of 59% and 90%, respectively, on the training set and
      80% and 100%, respectively, on the testing set. The proteomic classification rule
      performed with similar accuracy in low- and high-grade bladder carcinomas. In
      addition, we used hierarchical clustering with all 473 protein peaks on 65 benign
      voided urine samples, 88 samples from patients with clinically evident bladder
      cancer, and 127 samples from patients with a history of bladder cancer to
      classify the samples into Cluster A or B. The tumors in Cluster B were
      characterized by clinically aggressive behavior with significantly shorter
      metastasis-free and disease-specific survival.

PMID- 22879989
TI  - FOXA1 promotes tumor progression in prostate cancer via the insulin-like growth
      factor binding protein 3 pathway.
AB  - Fork-head box protein A1 (FOXA1) is a "pioneer factor" that is known to bind to
      the androgen receptor (AR) and regulate the transcription of AR-specific genes.
      However, the precise role of FOXA1 in prostate cancer (PC) remains unknown. In
      this study, we report that FOXA1 plays a critical role in PC cell proliferation.
      The expression of FOXA1 was higher in PC than in normal prostate tissues (P =
      0.0002), and, using immunohistochemical analysis, we found that FOXA1 was
      localized in the nucleus. FOXA1 expression levels were significantly correlated
      with both PSA and Gleason scores (P = 0.016 and P = 0.031, respectively).
      Moreover, FOXA1 up-regulation was a significant factor in PSA failure (P =
      0.011). Depletion of FOXA1 in a prostate cancer cell line (LNCaP) using small
      interfering RNA (siRNA) significantly inhibited AR activity, led to cell-growth
      suppression, and induced G0/G1 arrest. The anti-proliferative effect of FOXA1
      siRNA was mediated through insulin-like growth factor binding protein 3 (IGFBP
      3). An increase in IGFBP-3, mediated by depletion of FOXA1, inhibited
      phosphorylation of MAPK and Akt, and increased expression of the cell cycle
      regulators p21 and p27. We also found that the anti-proliferative effect of FOXA1
      depletion was significantly reversed by simultaneous siRNA depletion of IGFBP-3.
      These findings provide direct physiological and molecular evidence for a role of
      FOXA1 in controlling cell proliferation through the regulation of IGFBP-3
      expression in PC.

PMID- 22879990
TI  - How did the TB patients reach DOTS services in Delhi? A study of patient
      treatment seeking behavior.
AB  - SETTING: Revised National Tuberculosis Control Programme (RNTCP), Delhi, India.
      OBJECTIVE: To ascertain the number and sequence of providers visited by TB
      patients before availing treatment services from DOTS; to describe the duration
      between onset of symptoms to treatment. STUDY DESIGN: A cross sectional,
      qualitative study. Information was gathered through in-depth interviews of TB
      patients registered during the month of Oct, 2012 for availing TB treatment under
      the Revised National TB Control Programme from four tuberculosis diagnosis and
      treatment centers in Delhi. RESULTS: Out of the 114 patients who registered, 108
      participated in the study. The study showed that informal providers and retail
      chemists were the first point of contact and source of clinical advice for two
      third of the patients, while the rest sought medical care from qualified
      providers directly. Most patients sought medical care from more than two
      providers, before being diagnosed as TB. Female TB patients and patients with
      extra-pulmonary TB had long mean duration between onset of symptoms to initiation
      of treatment (6.3 months and 8.4 months respectively). CONCLUSION: The pathways
      followed by TB patients, illustrated in this study, provide valuable lessons on
      the importance of different types of providers (both formal and informal) in the
      health system in a society like India and the delays in the diagnosis and
      treatment of tuberculosis.

PMID- 22879991
TI  - Testing the effects of an introduced palm on a riparian invertebrate community in
      southern California.
AB  - Despite the iconic association of palms with semi-arid regions, most are
      introduced and can invade natural areas. Along the San Diego River (San Diego,
      California, USA), the introduced Canary Island date palm (Phoenix canariensis)
      forms dense patches among native riparian shrubs like arroyo willow (Salix
      lasiolepis). The structural differences between the palm and native shrubs are
      visually obvious, but little is known about palm's effects on the ecosystem. We
      tested for the effects of the palm on a riparian invertebrate community in June
      2011 by comparing the faunal and environmental variables associated with palm and
      willow canopies, trunks and ground beneath each species. The palm invertebrate
      community had lower abundance and diversity, fewer taxa feeding on the host
      (e.g., specialized hemipterans), and more taxa likely using only the plant's
      physical structure (e.g., web-builders, oak moths, willow hemipterans). There
      were no observed effects on the ground-dwelling fauna. Faunal differences were
      due to the physical and trophic changes associated with palm presence, namely
      increased canopy density, unpalatable leaves, trunk rugosity, and litter
      accumulations. Palm presence and resulting community shifts may have further
      ecosystem-level effects through alteration of physical properties, food, and
      structural resources. These results were consistent with a recent study of
      invasive palm effects on desert spring arthropods, illustrating that effects may
      be relatively generalizable. Since spread of the palm is largely localized, but
      effects are dramatic where it does occur, we recommend combining our results with
      several further investigations in order to prioritize management decisions.

PMID- 22879992
TI  - New robust face recognition methods based on linear regression.
AB  - Nearest subspace (NS) classification based on linear regression technique is a
      very straightforward and efficient method for face recognition. A recently
      developed NS method, namely the linear regression-based classification (LRC),
      uses downsampled face images as features to perform face recognition. The basic
      assumption behind this kind method is that samples from a certain class lie on
      their own class-specific subspace. Since there are only few training samples for
      each individual class, which will cause the small sample size (SSS) problem, this
      problem gives rise to misclassification of previous NS methods. In this paper, we
      propose two novel LRC methods using the idea that every class-specific subspace
      has its unique basis vectors. Thus, we consider that each class-specific subspace
      is spanned by two kinds of basis vectors which are the common basis vectors
      shared by many classes and the class-specific basis vectors owned by one class
      only. Based on this concept, two classification methods, namely robust LRC 1 and
      2 (RLRC 1 and 2), are given to achieve more robust face recognition. Unlike some
      previous methods which need to extract class-specific basis vectors, the proposed
      methods are developed merely based on the existence of the class-specific basis
      vectors but without actually calculating them. Experiments on three well known
      face databases demonstrate very good performance of the new methods compared with
      other state-of-the-art methods.

PMID- 22879993
TI  - Molecular and clinical characterization of the variable phenotype in Korean
      families with hearing loss associated with the mitochondrial A1555G mutation.
AB  - Hearing loss, which is genetically heterogeneous, can be caused by mutations in
      the mitochondrial DNA (mtDNA). The A1555G mutation of the 12S ribosomal RNA
      (rRNA) gene in the mtDNA has been associated with both aminoglycoside-induced and
      non-syndromic hearing loss in many ethnic populations. Here, we report for the
      first time the clinical and genetic characterization of nine Korean pedigrees
      with aminoglycoside-induced and non-syndromic hearing loss. These Korean families
      carry in the A1555G mutation of 12S rRNA gene and exhibit variable penetrance and
      expressivity of hearing loss. Specifically, the penetrance of hearing loss in
      these families ranged between 28.6% and 75%, with an average of 60.8%. These
      results were higher than the 29.8% penetrance that was previously reported in a
      Chinese population but similar to the 65.4% and 54.1% penetrance observed in a
      large Arab-Israeli population and nineteen Spanish pedigrees, respectively. The
      mutational analysis of the complete mtDNA genome in these families showed that
      the haplogroups of the Korean population, which belongs to the eastern Asian
      population, were similar to those of the Chinese population but different from
      the Spanish population, which belongs to the European-Caucasian population. The
      mtDNA variants that may act as modifier factors were also found to be similar to
      the Chinese population. Although the mtDNA haplogroups and variants were similar
      to the eastern Asian population, we did find some differing phenotypes, although
      some subjects had the same variants. This result suggests that both the ethnic
      background and environmental factors lead to a variable phenotype of the A1555G
      mutation.

PMID- 22879994
TI  - The dose-dependent immunoregulatory effects of the nitric oxide synthase
      inhibitor N(G)-nitro-L-arginine methyl ester in rats with sub-acute peritonitis.
AB  - BACKGROUND: Chronic inflammation accompanied by arginine deficiency, immune
      dysfunction, and excess nitric oxide (NO) production is a clinical condition
      found in patients with peritonitis. A previous study showed that the nonselective
      NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) may facilitate the
      metabolism of the immune nutrient arginine without altering NO homeostasis in
      rats with sub-acute peritonitis. Here, we investigated the effects of L-NAME on
      the immunocytic subpopulation distribution and response. MATERIALS AND METHODS:
      Male Wistar rats with cecal puncture-induced peritonitis were administered
      parenteral nutrition solutions supplemented with 0 (CPP group), 5 (LNA group), 25
      (MNA group) or 50 (HNA group) mg . kg(-1) . day(-1) of L-NAME for 7 days.
      Parenteral-fed sham-operated rats (TPN group) and orally-fed healthy rats (R
      group) were included as controls. RESULTS: The TPN group had significantly
      increased spleen weights and levels of plasma nitrite/nitrate (NOx), circulating
      white blood cells (WBC), and splenocytic T cells, as well as significantly
      decreased levels of cytotoxic T- and B-leukocytes and B-splenocytes compared to
      the R group. The CPP group had significantly decreased levels of plasma NOx and
      concanavalin (Con) A-stimulated interferon (IFN)-gamma and interleukin (IL)-2
      production by leukocytes and significantly increased production of Con A
      stimulated tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS)
      stimulated IFN-gamma in the leukocytes. In addition, the LNA and MNA groups had
      significantly decreased spontaneous IL-6 and Con A-stimulated TNF-alpha and IFN
      gamma production by the leukocytes while the HNA group had significantly
      increased LPS-stimulated TNF-alpha and Con A-stimulated IFN-gamma and IL-2
      production by the splenocytes compared to the CPP group. CONCLUSIONS: Low-dose L
      NAME infusion may suppress proinflammatory and T-helper-1 (Th1) response in
      leukocytes, and high-dose infusion may activate the proinflammatory response in
      splenic macrophages and Th1 response in T-splenocytes in rats with sub-acute
      peritonitis.

PMID- 22879995
TI  - Computational identification of novel amino-acid interactions in HIV Gag via
      correlated evolution.
AB  - Pairs of amino acid positions that evolve in a correlated manner are proposed to
      play important roles in protein structure or function. Methods to detect them
      might fare better with families for which sequences of thousands of closely
      related homologs are available than families with only a few distant relatives.
      We applied co-evolution analysis to thousands of sequences of HIV Gag, finding
      that the most significantly co-evolving positions are proximal in the quaternary
      structures of the viral capsid. A reduction in infectivity caused by mutating one
      member of a significant pair could be rescued by a compensatory mutation of the
      other.

PMID- 22879996
TI  - Perfluorinated compounds in umbilical cord blood and adverse birth outcomes.
AB  - BACKGROUND: Previous animal studies have shown that perfluorinated compounds
      (PFCs) have adverse impacts on birth outcomes, but the results have been
      inconclusive in humans. We investigated associations between prenatal exposure to
      perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic
      acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. METHODS: In
      total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study
      (TBPS). Demographic data were obtained by interviewing mothers using a structured
      questionnaire and birth outcomes were extracted from medical records. Cord blood
      was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance
      liquid chromatography/tandem mass spectrometry. RESULTS: The geometric mean
      (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma
      were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively.
      Only PFOS levels were found to be inversely associated with gestational age,
      birth weight, and head circumference [per ln unit: adjusted beta (95% confidence
      interval, CI) = -0.37 (-0.60, -0.13) wks, -110.2 (-176.0, -44.5) gm and -0.25 (
      0.46, -0.05) cm]. Additionally, the odds ratio of preterm birth, low birth
      weight, and small for gestational age increased with PFOS exposure [per ln unit:
      adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27
      (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response
      relation was observed. However, PFOA, PFNA, and PFUA were not observed to have
      any convincing impact on birth outcomes. CONCLUSIONS: An adverse dose-dependent
      association was observed between prenatal PFOS exposure and birth outcomes.
      However, no associations were found for the other examined PFCs.

PMID- 22879997
TI  - MyD88-dependent signaling influences fibrosis and alternative macrophage
      activation during Staphylococcus aureus biofilm infection.
AB  - Bacterial biofilms represent a significant therapeutic challenge based on their
      ability to evade host immune and antibiotic-mediated clearance. Recent studies
      have implicated IL-1beta in biofilm containment, whereas Toll-like receptors
      (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R)
      and most TLRs impinge on MyD88-dependent signaling pathways, yet the role of this
      key adaptor in modulating the host response to biofilm growth is unknown.
      Therefore, we examined the course of S. aureus catheter-associated biofilm
      infection in MyD88 knockout (KO) mice. MyD88 KO animals displayed significantly
      increased bacterial burdens on catheters and surrounding tissues during early
      infection, which coincided with enhanced dissemination to the heart and kidney
      compared to wild type (WT) mice. The expression of several proinflammatory
      mediators, including IL-6, IFN-gamma, and CXCL1 was significantly reduced in
      MyD88 KO mice, primarily at the later stages of infection. Interestingly,
      immunofluorescence staining of biofilm-infected tissues revealed increased
      fibrosis in MyD88 KO mice concomitant with enhanced recruitment of alternatively
      activated M2 macrophages. Taken in the context of previous studies with IL-1beta,
      TLR2, and TLR9 KO mice, the current report reveals that MyD88 signaling is a
      major effector pathway regulating fibrosis and macrophage polarization during
      biofilm formation. Together these findings represent a novel example of the
      divergence between TLR and MyD88 action in the context of S. aureus biofilm
      infection.

PMID- 22879998
TI  - Transient knockdown of tyrosine hydroxylase during development has persistent
      effects on behaviour in adult zebrafish (Danio rerio).
AB  - Abnormal dopamine (DA) signaling is often suggested as causative in
      schizophrenia. The other prominent hypothesis for this disorder, largely driven
      by epidemiological data, is that certain adverse events during the early stages
      of brain development increase an individual's risk of developing schizophrenia
      later in life. However, the clinical and preclinical literature consistently
      implicates behavioural, cognitive, and pharmacological abnormalities, implying
      that DA signaling is abnormal in the adult brain. How can we reconcile these two
      major hypotheses underlying much of the clinical and basic research into
      schizophrenia? In this study we have transiently knocked down tyrosine
      hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the
      early stages of brain development in zebrafish using morpholinos. We show that by
      adulthood, TH and DA levels have returned to normal and basic DA-mediated
      behaviours, such as locomotion, are also normal. However, when they were exposed
      to a novel environment the levels of freezing and immediate positioning in deeper
      zones were significantly reduced in these adult fish. The neurochemistry
      underlying these behaviours is complex, and the exact mechanisms for these
      abnormal behaviours remains unknown. This study demonstrates that early transient
      alterations in DA ontogeny can produce persistent alterations in adult brain
      function and suggests that the zebrafish may be a promising model animal for
      future studies directed at clarifying the basic neurodevelopmental mechanisms
      behind complex psychiatric disease.

PMID- 22879999
TI  - Novel nuclear localization and potential function of insulin-like growth factor-1
      receptor/insulin receptor hybrid in corneal epithelial cells.
AB  - BACKGROUND: Type I insulin-like growth factor receptor (IGF-1R) and insulin
      receptor (INSR) are highly homologous molecules, which can heterodimerize to form
      an IGF-1R/INSR hybrid (Hybrid-R). The presence and biological significance of the
      Hybrid-R in human corneal epithelium has not yet been established. In addition,
      while nuclear localization of IGF-1R was recently reported in cancer cells and
      human corneal epithelial cells, the function and profile of nuclear IGF-1R is
      unknown. In this study, we characterized the nuclear localization and function of
      the Hybrid-R and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human
      corneal epithelium. METHODOLOGY/PRINCIPLE FINDINGS: IGF-1-mediated signaling and
      cell growth were examined in a human telomerized corneal epithelial (hTCEpi) cell
      line using co-immunoprecipitation, immunoblotting and cell proliferation assays.
      The presence of Hybrid-R in hTCEpi and primary cultured human corneal epithelial
      cells was confirmed by immunofluorescence and reciprocal immunoprecipitation of
      whole cell lysates. We found that IGF-1 stimulated Akt and promoted cell growth
      through IGF-1R activation, which was independent of the Hybrid-R. The presence of
      Hybrid-R, but not IGF-1R/IGF-1R, was detected in nuclear extracts. Knockdown of
      INSR by small interfering RNA resulted in depletion of the INSR/INSR and
      preferential formation of Hybrid-R. Chromatin-immunoprecipitation sequencing
      assay with anti-IGF-1R or anti-INSR was subsequently performed to identify
      potential genomic targets responsible for critical homeostatic regulatory
      pathways. CONCLUSION/SIGNIFICANCE: In contrast to previous reports on nuclear
      localized IGF-1R, this is the first report identifying the nuclear localization
      of Hybrid-R in an epithelial cell line. The identification of a nuclear Hybrid-R
      and novel genomic targets suggests that IGF-1R traffics to the nucleus as an IGF
      1R/INSR heterotetrameric complex to regulate corneal epithelial homeostatic
      pathways. The development of novel therapeutic strategies designed to target the
      IGF-1/IGF-1R pathway must take into account the modulatory roles IGF-1R/INSR play
      in the epithelial cell nucleus.

PMID- 22880000
TI  - The influence of socioeconomic status on children's brain structure.
AB  - Children's cognitive abilities and school achievements are deeply affected by
      parental socioeconomic status (SES). Numerous studies have reported lower
      cognitive performance in relation to unfavorable environments, but little is
      known about the effects of SES on the child's neural structures. Here, we
      systematically explore the association between SES and brain anatomy through MRI
      in a group of 23 healthy 10-year-old children with a wide range of parental SES.
      We confirm behaviorally that language is one of the cognitive domains most
      affected by SES. Furthermore, we observe widespread modifications in children's
      brain structure. A lower SES is associated with smaller volumes of gray matter in
      bilateral hippocampi, middle temporal gyri, left fusiform and right inferior
      occipito-temporal gyri, according to both volume- and surface-based morphometry.
      Moreover, we identify local gyrification effects in anterior frontal regions,
      supportive of a potential developmental lag in lower SES children. In contrast,
      we found no significant association between SES and white matter architecture.
      These findings point to the potential neural mediators of the link between
      unfavourable environmental conditions and cognitive skills.

PMID- 22880001
TI  - Rapid detection of an ABT-737-sensitive primed for death state in cells using
      microplate-based respirometry.
AB  - Cells that exhibit an absolute dependence on the anti-apoptotic BCL-2 protein for
      survival are termed "primed for death" and are killed by the BCL-2 antagonist ABT
      737. Many cancers exhibit a primed phenotype, including some that are resistant
      to conventional chemotherapy due to high BCL-2 expression. We show here that 1)
      stable BCL-2 overexpression alone can induce a primed for death state and 2) that
      an ABT-737-induced loss of functional cytochrome c from the electron transport
      chain causes a reduction in maximal respiration that is readily detectable by
      microplate-based respirometry. Stable BCL-2 overexpression sensitized non
      tumorigenic MCF10A mammary epithelial cells to ABT-737-induced caspase-dependent
      apoptosis. Mitochondria within permeabilized BCL-2 overexpressing cells were
      selectively vulnerable to ABT-737-induced cytochrome c release compared to those
      from control-transfected cells, consistent with a primed state. ABT-737 treatment
      caused a dose-dependent impairment of maximal O(2) consumption in MCF10A BCL-2
      overexpressing cells but not in control-transfected cells or in immortalized
      mouse embryonic fibroblasts lacking both BAX and BAK. This impairment was rescued
      by delivering exogenous cytochrome c to mitochondria via saponin-mediated plasma
      membrane permeabilization. An ABT-737-induced reduction in maximal O(2)
      consumption was also detectable in SP53, JeKo-1, and WEHI-231 B-cell lymphoma
      cell lines, with sensitivity correlating with BCL-2:MCL-1 ratio and with
      susceptibility (SP53 and JeKo-1) or resistance (WEHI-231) to ABT-737-induced
      apoptosis. Multiplexing respirometry assays to ELISA-based determination of
      cytochrome c redistribution confirmed that respiratory inhibition was associated
      with cytochrome c release. In summary, cell-based respiration assays were able to
      rapidly identify a primed for death state in cells with either artificially
      overexpressed or high endogenous BCL-2. Rapid detection of a primed for death
      state in individual cancers by "bioenergetics-based profiling" may eventually
      help identify the subset of patients with chemoresistant but primed tumors who
      can benefit from treatment that incorporates a BCL-2 antagonist.

PMID- 22880002
TI  - Platelet-derived growth factor over-expression in retinal progenitors results in
      abnormal retinal vessel formation.
AB  - Platelet-derived growth factor (PDGF) plays an important role in development of
      the central nervous system, including the retina. Excessive PDGF signaling is
      associated with proliferative retinal disorders. We reported previously that
      transgenic mice in which PDGF-B was over-expressed under control of the nestin
      enhancer, nes/tk-PdgfB-lacZ, exhibited enhanced apoptosis in the developing
      corpus striatum. These animals display enlarged lateral ventricles after birth as
      well as behavioral aberrations as adults. Here, we report that in contrast to the
      relatively mild central nervous system phenotype, development of the retina is
      severely disturbed in nes/tk-PdgfB-lacZ mice. In transgenic retinas all nuclear
      layers were disorganized and photoreceptor segments failed to develop properly.
      Since astrocyte precursor cells did not populate the retina, retinal vascular
      progenitors could not form a network of vessels. With time, randomly distributed
      vessels resembling capillaries formed, but there were no large trunk vessels and
      the intraocular pressure was reduced. In addition, we observed a delayed
      regression of the hyaloid vasculature. The prolonged presence of this structure
      may contribute to the other abnormalities observed in the retina, including the
      defective lamination.

PMID- 22880003
TI  - Characterization of the Nrt2.6 gene in Arabidopsis thaliana: a link with plant
      response to biotic and abiotic stress.
AB  - The high affinity nitrate transport system in Arabidopsis thaliana involves one
      gene and potentially seven genes from the NRT1 and NRT2 family, respectively.
      Among them, NRT2.1, NRT2.2, NRT2.4 and NRT2.7 proteins have been shown to
      transport nitrate and are localized on the plasmalemma or the tonoplast
      membranes. NRT2.1, NRT2.2 and NRT2.4 play a role in nitrate uptake from soil
      solution by root cells while NRT2.7 is responsible for nitrate loading in the
      seed vacuole. We have undertaken the functional characterization of a third
      member of the family, the NRT2.6 gene. NRT2.6 was weakly expressed in most plant
      organs and its expression was higher in vegetative organs than in reproductive
      organs. Contrary to other NRT2 members, NRT2.6 expression was not induced by
      limiting but rather by high nitrogen levels, and no nitrate-related phenotype was
      found in the nrt2.6-1 mutant. Consistently, the over-expression of the gene
      failed to complement the nitrate uptake defect of an nrt2.1-nrt2.2 double mutant.
      The NRT2.6 expression is induced after inoculation of Arabidopsis thaliana by the
      phytopathogenic bacterium Erwinia amylovora. Interestingly, plants with a
      decreased NRT2.6 expression showed a lower tolerance to pathogen attack. A
      correlation was found between NRT2.6 expression and ROS species accumulation in
      response to infection by E. amylovora and treatment with the redox-active
      herbicide methyl viologen, suggesting a probable link between NRT2.6 activity and
      the production of ROS in response to biotic and abiotic stress.

PMID- 22880004
TI  - Mouse p53-deficient cancer models as platforms for obtaining genomic predictors
      of human cancer clinical outcomes.
AB  - Mutations in the TP53 gene are very common in human cancers, and are associated
      with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or
      that express mutant Trp53 transgenes produce tumours with malignant features in
      many organs. We previously showed the transcriptome of a p53-deficient mouse skin
      carcinoma model to be similar to those of human cancers with TP53 mutations and
      associated with poor clinical outcomes. This report shows that much of the 682
      gene signature of this murine skin carcinoma transcriptome is also present in
      breast and lung cancer mouse models in which p53 is inhibited. Further, we report
      validated gene-expression-based tests for predicting the clinical outcome of
      human breast and lung adenocarcinoma. It was found that human patients with
      cancer could be stratified based on the similarity of their transcriptome with
      the mouse skin carcinoma 682-gene signature. The results also provide new targets
      for the treatment of p53-defective tumours.

PMID- 22880005
TI  - Adaptive capacity of the habitat modifying sea urchin Centrostephanus rodgersii
      to ocean warming and ocean acidification: performance of early embryos.
AB  - BACKGROUND: Predicting effects of rapid climate change on populations depends on
      measuring the effects of climate stressors on performance, and potential for
      adaptation. Adaptation to stressful climatic conditions requires heritable
      genetic variance for stress tolerance present in populations.
      METHODOLOGY/PRINCIPAL FINDINGS: We quantified genetic variation in tolerance of
      early development of the ecologically important sea urchin Centrostephanus
      rodgersii to near-future (2100) ocean conditions projected for the southeast
      Australian global change hot spot. Multiple dam-sire crosses were used to
      quantify the interactive effects of warming (+2-4  degrees C) and acidification (
      0.3-0.5 pH units) across twenty-seven family lines. Acidification, but not
      temperature, decreased the percentage of cleavage stage embryos. In contrast,
      temperature, but not acidification decreased the percentage of gastrulation.
      Cleavage success in response to both stressors was strongly affected by sire
      identity. Sire and dam identity significantly affected gastrulation and both
      interacted with temperature to determine developmental success. Positive genetic
      correlations for gastrulation indicated that genotypes that did well at lower pH
      also did well in higher temperatures. CONCLUSIONS/SIGNIFICANCE: Significant
      genotype (sire) by environment interactions for both stressors at gastrulation
      indicated the presence of heritable variation in thermal tolerance and the
      ability of embryos to respond to changing environments. The significant influence
      of dam may be due to maternal provisioning (maternal genotype or environment)
      and/or offspring genotype. It appears that early development in this ecologically
      important sea urchin is not constrained in adapting to the multiple stressors of
      ocean warming and acidification. The presence of tolerant genotypes indicates the
      potential to adapt to concurrent warming and acidification, contributing to the
      resilience of C. rodgersii in a changing ocean.

PMID- 22880007
TI  - A neural network model of ventriloquism effect and aftereffect.
AB  - Presenting simultaneous but spatially discrepant visual and auditory stimuli
      induces a perceptual translocation of the sound towards the visual input, the
      ventriloquism effect. General explanation is that vision tends to dominate over
      audition because of its higher spatial reliability. The underlying neural
      mechanisms remain unclear. We address this question via a biologically inspired
      neural network. The model contains two layers of unimodal visual and auditory
      neurons, with visual neurons having higher spatial resolution than auditory ones.
      Neurons within each layer communicate via lateral intra-layer synapses; neurons
      across layers are connected via inter-layer connections. The network accounts for
      the ventriloquism effect, ascribing it to a positive feedback between the visual
      and auditory neurons, triggered by residual auditory activity at the position of
      the visual stimulus. Main results are: i) the less localized stimulus is strongly
      biased toward the most localized stimulus and not vice versa; ii) amount of the
      ventriloquism effect changes with visual-auditory spatial disparity; iii)
      ventriloquism is a robust behavior of the network with respect to parameter value
      changes. Moreover, the model implements Hebbian rules for potentiation and
      depression of lateral synapses, to explain ventriloquism aftereffect (that is,
      the enduring sound shift after exposure to spatially disparate audio-visual
      stimuli). By adaptively changing the weights of lateral synapses during cross
      modal stimulation, the model produces post-adaptive shifts of auditory
      localization that agree with in-vivo observations. The model demonstrates that
      two unimodal layers reciprocally interconnected may explain ventriloquism effect
      and aftereffect, even without the presence of any convergent multimodal area. The
      proposed study may provide advancement in understanding neural architecture and
      mechanisms at the basis of visual-auditory integration in the spatial realm.

PMID- 22880006
TI  - Nuclear-cytoplasmic trafficking of NTF2, the nuclear import receptor for the
      RanGTPase, is subjected to regulation.
AB  - NTF2 is a cytosolic protein responsible for nuclear import of Ran, a small Ras
      like GTPase involved in a number of critical cellular processes, including cell
      cycle regulation, chromatin organization during mitosis, reformation of the
      nuclear envelope following mitosis, and controlling the directionality of
      nucleocytoplasmic transport. Herein, we provide evidence for the first time that
      translocation of the mammalian NTF2 from the nucleus to the cytoplasm to collect
      Ran in the GDP form is subjected to regulation. Treatment of mammalian cells with
      polysorbitan monolaurate was found to inhibit nuclear export of tRNA and
      proteins, which are processes dependent on RanGTP in the nucleus, but not nuclear
      import of proteins. Inhibition of the export processes by polysorbitan
      monolaurate is specific and reversible, and is caused by accumulation of Ran in
      the cytoplasm because of a block in translocation of NTF2 to the cytoplasm.
      Nuclear import of Ran and the nuclear export processes are restored in
      polysorbitan monolaurate treated cells overproducing NTF2. Moreover, increased
      phosphorylation of a phospho-tyrosine protein and several phospho-threonine
      proteins was observed in polysorbitan monolaurate treated cells. Collectively,
      these findings suggest that nucleocytoplasmic translocation of NTF2 is regulated
      in mammalian cells, and may involve a tyrosine and/or threonine kinase-dependent
      signal transduction mechanism(s).

PMID- 22880009
TI  - Enlargement of the field of view and maintenance of a high signal-to-noise ratio
      using a two-element high-Tc superconducting array in a 3T MRI.
AB  - This study examines the enlargement of the field of view (FOV) and the
      maintenance of a high signal-to-noise ratio (SNR) through the use of two high
      temperature superconducting (HTS) resonators in a 3T MRI. Two
      Bi(2)Sr(2)Ca(2)Cu(3)O(x) (Bi-2223) surface resonators, each of 4-cm diameter,
      were used in a 3T MRI. Professionally made copper resonators operate at 300 K,
      but each Bi-2223 resonator, operated at 77 K and demonstrated a 3.75 fold
      increase in SNR gain. For the same scanning time, the SNR of the images of a
      rat's brain and back, obtained using two small Bi-2223 surface resonators, was
      higher than that obtained using a single 8-cm surface resonator.

PMID- 22880008
TI  - Classical macrophage activation up-regulates several matrix metalloproteinases
      through mitogen activated protein kinases and nuclear factor-kappaB.
AB  - Remodelling of the extracellular matrix (ECM) and cell surface by matrix
      metalloproteinases (MMPs) is an important function of monocytes and macrophages.
      Recent work has emphasised the diverse roles of classically and alternatively
      activated macrophages but the consequent regulation of MMPs and their inhibitors
      has not been studied comprehensively. Classical activation of macrophages derived
      in vitro from un-fractionated CD16(+/-) or negatively-selected CD16(-)
      macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP
      3 steady-state mRNA levels. Bacterial lipopolysaccharide, IL-1 and TNFalpha were
      more effective than interferongamma except for the effects on MMP-25, and TIMP-3.
      By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP
      -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during
      classical activation depended on mitogen activated protein kinases,
      phosphoinositide-3-kinase and inhibitor of kappaB kinase-2. Effects of
      interferongamma depended on janus kinase-2. Where investigated, similar effects
      were seen on protein concentrations and collagenase activity. Moreover, activity
      of MMP-1 and -10 co-localised with markers of classical activation in human
      atherosclerotic plaques in vivo. In conclusion, classical macrophage activation
      selectively up-regulates several MMPs in vitro and in vivo and down-regulates
      TIMP-3, whereas alternative activation up-regulates a distinct group of MMPs and
      TIMP-3. The signalling pathways defined here suggest targets for selective
      modulation of MMP activity.

PMID- 22880010
TI  - Waking action of ursodeoxycholic acid (UDCA) involves histamine and GABAA
      receptor block.
AB  - Since ancient times ursodeoxycholic acid (UDCA), a constituent of bile, is used
      against gallstone formation and cholestasis. A neuroprotective action of UDCA was
      demonstrated recently in models of Alzheimer's disease and retinal degeneration.
      The mechanisms of UDCA action in the nervous system are poorly understood. We
      show now that UDCA promotes wakefulness during the active period of the day,
      lacking this activity in histamine-deficient mice. In cultured hypothalamic
      neurons UDCA did not affect firing rate but synchronized the firing, an effect
      abolished by the GABA(A)R antagonist gabazine. In histaminergic neurons recorded
      in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In
      acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and
      sIPSCs starting at 10 uM (IC(50) = 70 uM) and did not affect NMDA- and AMPA
      receptor mediated currents at 100 uM. Recombinant GABA(A) receptors composed of
      alpha1, beta1-3 and gamma2L subunits expressed in HEK293 cells displayed a
      sensitivity to UDCA similar to that of native GABA(A) receptors. The mutation
      alpha1V256S, known to reduce the inhibitory action of pregnenolone sulphate,
      reduced the potency of UDCA. The mutation alpha1Q241L, which abolishes GABA(A)R
      potentiation by several neurosteroids, had no effect on GABA(A)R inhibition by
      UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least
      partially of the histaminergic system via GABA(A) receptors.

PMID- 22880011
TI  - Tgf-beta induced Erk phosphorylation of smad linker region regulates smad
      signaling.
AB  - The Transforming Growth Factor-Beta (TGF-beta) family is involved in regulating a
      variety of cellular processes such as apoptosis, differentiation, and
      proliferation. TGF-beta binding to a Serine/Threonine kinase receptor complex
      causes the recruitment and subsequent activation of transcription factors known
      as smad2 and smad3. These proteins subsequently translocate into the nucleus to
      negatively or positively regulate gene expression. In this study, we define a
      second signaling pathway leading to TGF-beta receptor activation of Extracellular
      Signal Regulated Kinase (Erk) in a cell-type dependent manner. TGF-beta induced
      Erk activation was found in phenotypically normal mesenchymal cells, but not
      normal epithelial cells. By activating phosphotidylinositol 3-kinase (PI3K), TGF
      beta stimulates p21-activated kinase2 (Pak2) to phosphorylate c-Raf, ultimately
      resulting in Erk activation. Activation of Erk was necessary for TGF-beta induced
      fibroblast replication. In addition, Erk phosphorylated the linker region of
      nuclear localized smads, resulting in increased half-life of C-terminal phospho
      smad 2 and 3 and increased duration of smad target gene transcription. Together,
      these data show that in mesenchymal cell types the TGF-beta/PI3K/Pak2/Raf/MEK/Erk
      pathway regulates smad signaling, is critical for TGF-beta-induced growth and is
      part of an integrated signaling web containing multiple interacting pathways
      rather than discrete smad/non-smad pathways.

PMID- 22880012
TI  - Divergent effects of mycobacterial cell wall glycolipids on maturation and
      function of human monocyte-derived dendritic cells.
AB  - BACKGROUND: Mycobacterium tuberculosis (Mtb) is able to evade the immune defenses
      and may persist for years, decades and even lifelong in the infected host. Mtb
      cell wall components may contribute to such persistence by modulating several
      pivotal types of immune cells. Dendritic cells (DCs) are the most potent antigen
      presenting cells and hence play a crucial role in the initial immune response to
      infections by connecting the innate with the adaptive immune system. PRINCIPAL
      FINDINGS: We investigated the effects of two of the major mycobacterial cell wall
      associated types of glycolipids, mannose-capped lipoarabinomannan (ManLAM) and
      phosphatidylinositol mannosides (PIMs) purified from the Mtb strains H37Rv and
      Mycobacterium bovis, on the maturation and cytokine profiles of immature human
      monocyte-derived DCs. ManLAM from Mtb H37Rv stimulated the release of pro
      inflammatory cytokines TNF, IL-12, and IL-6 and expression of co-stimulatory
      (CD80, CD86) and antigen-presenting molecules (MHC class II). ManLAM from M.
      bovis also induced TNF, IL-12 and IL-6 but at significantly lower levels.
      Importantly, while ManLAM was found to augment LPS-induced DC maturation and pro
      inflammatory cytokine production, addition of PIMs from both Mtb H37Rv and M.
      bovis strongly reduced this stimulatory effect. CONCLUSIONS: These results
      indicate that the mycobacterial cell wall contains macromolecules of glycolipid
      nature which are able to induce strong and divergent effects on human DCs; i.e
      while ManLAM is immune-stimulatory, PIMs act as powerful inhibitors of DC
      cytokine responses. Thus PIMs may be important Mtb-associated virulence factors
      contributing to the pathogenesis of tuberculosis disease. These findings may also
      aid in the understanding of some earlier conflicting reports on the
      immunomodulatory effects exerted by different ManLAM preparations.

PMID- 22880013
TI  - Stromal expression of decorin, Semaphorin6D, SPARC, Sprouty1 and Tsukushi in
      developing prostate and decreased levels of decorin in prostate cancer.
AB  - BACKGROUND AND AIM: During prostate development, mesenchymal-epithelial
      interactions regulate organ growth and differentiation. In adult prostate,
      stromal-epithelial interactions are important for tissue homeostasis and also
      play a significant role in prostate cancer. In this study we have identified
      molecules that show a mesenchymal expression pattern in the developing prostate,
      and one of these showed reduced expression in prostate cancer stroma. METHODOLOGY
      AND PRINCIPAL FINDINGS: Five candidate molecules identified by transcript
      profiling of developmental prostate mesenchyme were selected using a wholemount
      in situ hybridisation screen and studied Decorin (Dcn), Semaphorin6D (Sema6D),
      SPARC/Osteonectin (SPARC), Sprouty1 (Spry-1) and Tsukushi (Tsku). Expression in
      rat tissues was evaluated using wholemount in situ hybridisation (postnatal day
      (P) 0.5) and immunohistochemistry (embryonic day (E) E17.5, E19.5; P0.5; P6; 28 &
      adult). Four candidates (Decorin, SPARC, Spry-1, Tsukushi) were immunolocalised
      in human foetal prostate (weeks 14, 16, 19) and expression of Decorin was
      evaluated on a human prostate cancer tissue microarray. In embryonic and
      perinatal rats Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi were expressed
      with varying distribution patterns throughout the mesenchyme at E17.5, E19.5,
      P0.5 and P6.5. In P28 and adult prostates there was either a decrease in the
      expression (Semaphorin6D) or a switch to epithelial expression of SPARC, and Spry
      1, whereas Decorin and Tsukushi were specific to mesenchyme/stroma at all ages.
      Expression of Decorin, SPARC, Spry-1 and Tsukushi in human foetal prostates
      paralleled that in rat. Decorin showed mesenchymal and stromal-specific
      expression at all ages and was further examined in prostate cancer, where stromal
      expression was significantly reduced compared with non-malignant prostate.
      CONCLUSION AND SIGNIFICANCE: We describe the spatio-temporal expression of
      Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate and
      observed similar mesenchymal expression patterns in rat and human. Additionally,
      Decorin showed reduced expression in prostate cancer stroma compared to non
      malignant prostate stroma.

PMID- 22880014
TI  - A comparison of computational methods for identifying virulence factors.
AB  - Bacterial pathogens continue to threaten public health worldwide today.
      Identification of bacterial virulence factors can help to find novel drug/vaccine
      targets against pathogenicity. It can also help to reveal the mechanisms of the
      related diseases at the molecular level. With the explosive growth in protein
      sequences generated in the postgenomic age, it is highly desired to develop
      computational methods for rapidly and effectively identifying virulence factors
      according to their sequence information alone. In this study, based on the
      protein-protein interaction networks from the STRING database, a novel network
      based method was proposed for identifying the virulence factors in the proteomes
      of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C.
      jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark
      datasets derived from the aforementioned species, the identification accuracies
      achieved by the network-based method were around 0.9, significantly higher than
      those by the sequence-based methods such as BLAST, feature selection and
      VirulentPred. Further analysis showed that the functional associations such as
      the gene neighborhood and co-occurrence were the primary associations between
      these virulence factors in the STRING database. The high success rates indicate
      that the network-based method is quite promising. The novel approach holds high
      potential for identifying virulence factors in many other various organisms as
      well because it can be easily extended to identify the virulence factors in many
      other bacterial species, as long as the relevant significant statistical data are
      available for them.

PMID- 22880015
TI  - Structural and functional characterization of ribosomal protein gene introns in
      sponges.
AB  - Ribosomal protein genes (RPGs) are a powerful tool for studying intron evolution.
      They exist in all three domains of life and are much conserved. Accumulating
      genomic data suggest that RPG introns in many organisms abound with non-protein
      coding-RNAs (ncRNAs). These ancient ncRNAs are small nucleolar RNAs (snoRNAs)
      essential for ribosome assembly. They are also mobile genetic elements and
      therefore probably important in diversification and enrichment of transcriptomes
      through various mechanisms such as intron/exon gain/loss. snoRNAs in basal
      metazoans are poorly characterized. We examined 449 RPG introns, in total, from
      four demosponges: Amphimedon queenslandica, Suberites domuncula, Suberites ficus
      and Suberites pagurorum and showed that RPG introns from A. queenslandica share
      position conservancy and some structural similarity with "higher" metazoans.
      Moreover, our study indicates that mobile element insertions play an important
      role in the evolution of their size. In four sponges 51 snoRNAs were identified.
      The analysis showed discrepancies between the snoRNA pools of orthologous RPG
      introns between S. domuncula and A. queenslandica. Furthermore, these two sponges
      show as much conservancy of RPG intron positions between each other as between
      themselves and human. Sponges from the Suberites genus show consistency in RPG
      intron position conservation. However, significant differences in some of the
      orthologous RPG introns of closely related sponges were observed. This indicates
      that RPG introns are dynamic even on these shorter evolutionary time scales.

PMID- 22880016
TI  - Bacterial community dynamics in full-scale activated sludge bioreactors:
      operational and ecological factors driving community assembly and performance.
AB  - The assembling of bacterial communities in conventional activated sludge (CAS)
      bioreactors was thought, until recently, to be chaotic and mostly unpredictable.
      Studies done over the last decade have shown that specific, and often,
      predictable random and non-random factors could be responsible for that process.
      These studies have also motivated a "structure-function" paradigm that is yet to
      be resolved. Thus, elucidating the factors that affect community assembly in the
      bioreactors is necessary for predicting fluctuations in community structure and
      function. For this study activated sludge samples were collected during a one
      year period from two geographically distant CAS bioreactors of different size.
      Combining community fingerprinting analysis and operational parameters data with
      a robust statistical analysis, we aimed to identify relevant links between system
      performance and bacterial community diversity and dynamics. In addition to
      revealing a significant beta-diversity between the bioreactors' communities,
      results showed that the largest bioreactor had a less dynamic but more efficient
      and diverse bacterial community throughout the study. The statistical analysis
      also suggests that deterministic factors, as opposed to stochastic factors, may
      have a bigger impact on the community structure in the largest bioreactor.
      Furthermore, the community seems to rely mainly on mechanisms of resistance and
      functional redundancy to maintain functional stability. We suggest that the
      ecological theories behind the Island Biogeography model and the species-area
      relationship were appropriate to predict the assembly of bacterial communities in
      these CAS bioreactors. These results are of great importance for engineers and
      ecologists as they reveal critical aspects of CAS systems that could be applied
      towards improving bioreactor design and operation.

PMID- 22880017
TI  - Serotonin potentiates transforming growth factor-beta3 induced biomechanical
      remodeling in avian embryonic atrioventricular valves.
AB  - Embryonic heart valve primordia (cushions) maintain unidirectional blood flow
      during development despite an increasingly demanding mechanical environment.
      Recent studies demonstrate that atrioventricular (AV) cushions stiffen over
      gestation, but the molecular mechanisms of this process are unknown. Transforming
      growth factor-beta (TGFbeta) and serotonin (5-HT) signaling modulate tissue
      biomechanics of postnatal valves, but less is known of their role in the
      biomechanical remodeling of embryonic valves. In this study, we demonstrate that
      exogenous TGFbeta3 increases AV cushion biomechanical stiffness and residual
      stress, but paradoxically reduces matrix compaction. We then show that TGFbeta3
      induces contractile gene expression (RhoA, aSMA) and extracellular matrix
      expression (col1alpha2) in cushion mesenchyme, while simultaneously stimulating a
      two-fold increase in proliferation. Local compaction increased due to an elevated
      contractile phenotype, but global compaction appeared reduced due to
      proliferation and ECM synthesis. Blockade of TGFbeta type I receptors via
      SB431542 inhibited the TGFbeta3 effects. We next showed that exogenous 5-HT does
      not influence cushion stiffness by itself, but synergistically increases cushion
      stiffness with TGFbeta3 co-treatment. 5-HT increased TGFbeta3 gene expression and
      also potentiated TGFbeta3 induced gene expression in a dose-dependent manner.
      Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter
      (SERT), resulted in complete cessation of TGFbeta3 induced mechanical
      strengthening. Finally, systemic 5-HT administration in ovo induced cushion
      remodeling related defects, including thinned/atretic AV valves, ventricular
      septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in
      elevated remodeling gene expression and increased TGFbeta signaling activity,
      supporting our ex-vivo findings. Collectively, these results highlight TGFbeta/5
      HT signaling as a potent mechanism for control of biomechanical remodeling of AV
      cushions during development.

PMID- 22880018
TI  - Acoustic identification of individuals within large avian populations: a case
      study of the Brownish-flanked Bush Warbler, South-Central China.
AB  - Acoustic identification is increasingly being used as a non-invasive method for
      identifying individuals within avian populations. However, most previous studies
      have utilized small samples of individuals (<30). The feasibility of using
      acoustic identification of individuals in larger avian populations has never been
      seriously tested. In this paper, we assess the feasibility of using distinct
      acoustic signals to identify individuals in a large avian population (139 colour
      banded individuals) of Brownish-flanked Bush Warbler (Cettia fortipes) in the
      Dongzhai National Nature Reserve, south-central China. Most spectro-temporal
      variables we measured show greater variation among individuals than within
      individual. Although there was slight decline in the correct rate of individual
      identification with increasing sample sizes, the total mean correct rate yielded
      by discriminant function analysis was satisfactory, with more than 98% of songs
      correctly recognized to the corresponding individuals. We also found that using a
      part of randomly selected measured variables was sufficient to obtain a high
      correct rate of individual identification. We believe that our work will increase
      confidence in the use of using acoustic recognition techniques for avian
      population monitoring programs.

PMID- 22880019
TI  - Structural changes of gut microbiota during berberine-mediated prevention of
      obesity and insulin resistance in high-fat diet-fed rats.
AB  - Berberine, a major pharmacological component of the Chinese herb Coptis
      chinensis, which was originally used to treat bacterial diarrhea, has recently
      been demonstrated to be clinically effective in alleviating type 2 diabetes. In
      this study, we revealed that berberine effectively prevented the development of
      obesity and insulin resistance in high-fat diet (HFD)-fed rats, which showed
      decreased food intake. Increases in the levels of serum lipopolysaccharide
      binding protein, monocyte chemoattractant protein-1, and leptin and decrease in
      the serum level of adiponectin corrected for body fat in HFD-fed rats were also
      significantly retarded by the co-administration of berberine at 100 mg/kg body
      weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a
      significant reduction in the gut microbiota diversity of berberine-treated rats.
      UniFrac principal coordinates analysis revealed a marked shift of the gut
      microbiota structure in berberine-treated rats away from that of the controls.
      Redundancy analysis identified 268 berberine-responding operational taxonomic
      units (OTUs), most of which were essentially eliminated, whereas a few putative
      short-chain fatty acid (SCFA)-producing bacteria, including Blautia and
      Allobaculum, were selectively enriched, along with elevations of fecal SCFA
      concentrations. Partial least square regression models based on these 268 OTUs
      were established (Q(2)>0.6) for predicting the adiposity index, body weight,
      leptin and adiponectin corrected for body fat, indicating that these discrete
      phylotypes might have a close association with the host metabolic phenotypes.
      Taken together, our findings suggest that the prevention of obesity and insulin
      resistance by berberine in HFD-fed rats is at least partially mediated by
      structural modulation of the gut microbiota, which may help to alleviate
      inflammation by reducing the exogenous antigen load in the host and elevating
      SCFA levels in the intestine.

PMID- 22880021
TI  - Long-distance and frequent movements of the flying-fox Pteropus poliocephalus:
      implications for management.
AB  - Flying-foxes (Pteropodidae) are large bats capable of long-distance flight. Many
      species are threatened; some are considered pests. Effective conservation and
      management of flying-foxes are constrained by lack of knowledge of their ecology,
      especially of movement patterns over large spatial scales. Using satellite
      telemetry, we quantified long-distance movements of the grey-headed flying-fox
      Pteropus poliocephalus among roost sites in eastern Australia. Fourteen adult
      males were tracked for 2-40 weeks (mean 25 weeks). Collectively, these
      individuals utilised 77 roost sites in an area spanning 1,075 km by 128 km.
      Movement patterns varied greatly between individuals, with some travelling long
      distances. Five individuals travelled cumulative distances >1,000 km over the
      study period. Five individuals showed net displacements >300 km during one month,
      including one movement of 500 km within 48 hours. Seasonal movements were
      consistent with facultative latitudinal migration in part of the population.
      Flying-foxes shifted roost sites frequently: 64% of roost visits lasted <5
      consecutive days, although some individuals remained at one roost for several
      months. Modal 2-day distances between consecutive roosts were 21-50 km (mean 45
      km, range 3-166 km). Of 13 individuals tracked for >12 weeks, 10 moved >100 km in
      one or more weeks. Median cumulative displacement distances over 1, 10 and 30
      weeks were 0 km, 260 km and 821 km, respectively. On average, over increasing
      time-periods, one additional roost site was visited for each additional 100 km
      travelled. These findings explain why culling and relocation attempts have had
      limited success in resolving human-bat conflicts in Australia. Flying-foxes are
      highly mobile between camps and regularly travel long distances. Consequently,
      local control actions are likely to have only temporary effects on local flying
      fox populations. Developing alternative methods to manage these conflicts remains
      an important challenge that should be informed by a better understanding of the
      species' movement patterns.

PMID- 22880022
TI  - Vessel noise affects beaked whale behavior: results of a dedicated acoustic
      response study.
AB  - Some beaked whale species are susceptible to the detrimental effects of
      anthropogenic noise. Most studies have concentrated on the effects of military
      sonar, but other forms of acoustic disturbance (e.g. shipping noise) may disrupt
      behavior. An experiment involving the exposure of target whale groups to intense
      vessel-generated noise tested how these exposures influenced the foraging
      behavior of Blainville's beaked whales (Mesoplodon densirostris) in the Tongue of
      the Ocean (Bahamas). A military array of bottom-mounted hydrophones was used to
      measure the response based upon changes in the spatial and temporal pattern of
      vocalizations. The archived acoustic data were used to compute metrics of the
      echolocation-based foraging behavior for 16 targeted groups, 10 groups further
      away on the range, and 26 non-exposed groups. The duration of foraging bouts was
      not significantly affected by the exposure. Changes in the hydrophone over which
      the group was most frequently detected occurred as the animals moved around
      within a foraging bout, and their number was significantly less the closer the
      whales were to the sound source. Non-exposed groups also had significantly more
      changes in the primary hydrophone than exposed groups irrespective of distance.
      Our results suggested that broadband ship noise caused a significant change in
      beaked whale behavior up to at least 5.2 kilometers away from the vessel. The
      observed change could potentially correspond to a restriction in the movement of
      groups, a period of more directional travel, a reduction in the number of
      individuals clicking within the group, or a response to changes in prey movement.

PMID- 22880020
TI  - Investigation of the bacterial communities associated with females of Lutzomyia
      sand fly species from South America.
AB  - Phlebotomine sand flies are vectors of Leishmania that are acquired by the female
      sand fly during blood feeding on an infected mammal. Leishmania parasites develop
      exclusively in the gut lumen during their residence in the insect before
      transmission to a suitable host during the next blood feed. Female phlebotomine
      sand flies are blood feeding insects but their life style of visiting plants as
      well as animals, and the propensity for larvae to feed on detritus including
      animal faeces means that the insect host and parasite are exposed to a range of
      microorganisms. Thus, the sand fly microbiota may interact with the developing
      Leishmania population in the gut. The aim of the study was to investigate and
      identify the bacterial diversity associated with wild adult female Lutzomyia sand
      flies from different geographical locations in the New World. The bacterial
      phylotypes recovered from 16S rRNA gene clone libraries obtained from wild caught
      adult female Lutzomyia sand flies were estimated from direct band sequencing
      after denaturing gradient gel electrophoresis of bacterial 16 rRNA gene
      fragments. These results confirm that the Lutzomyia sand flies contain a limited
      array of bacterial phylotypes across several divisions. Several potential plant
      related bacterial sequences were detected including Erwinia sp. and putative
      Ralstonia sp. from two sand fly species sampled from 3 geographically separated
      regions in Brazil. Identification of putative human pathogens also demonstrated
      the potential for sand flies to act as vectors of bacterial pathogens of medical
      importance in addition to their role in Leishmania transmission.

PMID- 22880023
TI  - The expression of tubulin cofactor A (TBCA) is regulated by a noncoding antisense
      Tbca RNA during testis maturation.
AB  - BACKGROUND: Recently, long noncoding RNAs have emerged as pivotal molecules for
      the regulation of coding genes' expression. These molecules might result from
      antisense transcription of functional genes originating natural antisense
      transcripts (NATs) or from transcriptional active pseudogenes. TBCA interacts
      with beta-tubulin and is involved in the folding and dimerization of new tubulin
      heterodimers, the building blocks of microtubules. METHODOLOGY/PRINCIPAL
      FINDINGS: We found that the mouse genome contains two structurally distinct Tbca
      genes located in chromosomes 13 (Tbca13) and 16 (Tbca16). Interestingly, the two
      Tbca genes albeit ubiquitously expressed, present differential expression during
      mouse testis maturation. In fact, as testis maturation progresses Tbca13 mRNA
      levels increase progressively, while Tbca16 mRNA levels decrease. This suggests a
      regulatory mechanism between the two genes and prompted us to investigate the
      presence of the two proteins. However, using tandem mass spectrometry we were
      unable to identify the TBCA16 protein in testis extracts even in those
      corresponding to the maturation step with the highest levels of Tbca16
      transcripts. These puzzling results led us to re-analyze the expression of
      Tbca16. We then detected that Tbca16 transcription produces sense and natural
      antisense transcripts. Strikingly, the specific depletion by RNAi of these
      transcripts leads to an increase of Tbca13 transcript levels in a mouse
      spermatocyte cell line. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that
      Tbca13 mRNA levels are post-transcriptionally regulated by the sense and natural
      antisense Tbca16 mRNA levels. We propose that this regulatory mechanism operates
      during spermatogenesis, a process that involves microtubule rearrangements, the
      assembly of specific microtubule structures and requires critical TBCA levels.

PMID- 22880024
TI  - Prevalence and associated factors of diabetes and impaired fasting glucose in
      Chinese hypertensive adults aged 45 to 75 years.
AB  - OBJECTIVE: This study examined the prevalence of impaired fasting glucose (IFG)
      and diabetes and their associated factors in 17,184 Chinese hypertensive adults
      aged 45-75 years. METHODS: A cross-sectional investigation was carried out in a
      rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma
      glucose (FPG) >= 7.0 mmol/l] and IFG (6.1-6.9 mmol/l) were defined based on FPG
      concentration. Previously diagnosed diabetes was determined on the basis of self
      report. Total diabetes included both previously diagnosed diabetes and previously
      undiagnosed diabetes. RESULTS: The prevalence of previously diagnosed diabetes,
      undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About
      74.2% of the participants with diabetes had not previously been diagnosed. In the
      multivariable logistic-regression model, older age, men, antihypertensive
      treatment, obesity (BMI >= 25 kg/m(2)), abdominal obesity (waist circumference >=
      90 cm for men and >= 80 cm for women), non-current smoking, a family history of
      diabetes, higher heart rate, lower physical activity levels, and inland residence
      (versus coastal) were significantly associated with both total diabetes and
      previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate
      reductase (MTHFR) 677 TT genotype was an independent associated factor for total
      diabetes, and current alcohol drinking was an independent associated factor for
      previously undiagnosed diabetes. At the same time, older age, men, abdominal
      obesity, non-current smoking, current alcohol drinking, a family history of
      diabetes, higher heart rate, and inland residence (versus coastal) were important
      independent associated factors for IFG. CONCLUSION: In conclusion, we found a
      high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about
      three out of every four diabetic adults were undiagnosed. Our results suggest
      that population-level measures aimed at the prevention, identification (even if
      only based on the FPG evaluation), and treatment of diabetes should be urgently
      taken to overcome the diabetes epidemic in Chinese hypertensive adults.

PMID- 22880025
TI  - Atmospheric pressure plasma: a high-performance tool for the efficient removal of
      biofilms.
AB  - INTRODUCTION: The medical use of non-thermal physical plasmas is intensively
      investigated for sterilization and surface modification of biomedical materials.
      A further promising application is the removal or etching of organic substances,
      e.g., biofilms, from surfaces, because remnants of biofilms after conventional
      cleaning procedures are capable to entertain inflammatory processes in the
      adjacent tissues. In general, contamination of surfaces by micro-organisms is a
      major source of problems in health care. Especially biofilms are the most common
      type of microbial growth in the human body and therefore, the complete removal of
      pathogens is mandatory for the prevention of inflammatory infiltrate. Physical
      plasmas offer a huge potential to inactivate micro-organisms and to remove
      organic materials through plasma-generated highly reactive agents. METHOD: In
      this study a Candida albicans biofilm, formed on polystyrene (PS) wafers, as a
      prototypic biofilm was used to verify the etching capability of the atmospheric
      pressure plasma jet operating with two different process gases (argon and
      argon/oxygen mixture). The capability of plasma-assisted biofilm removal was
      assessed by microscopic imaging. RESULTS: The Candida albicans biofilm, with a
      thickness of 10 to 20 um, was removed within 300 s plasma treatment when oxygen
      was added to the argon gas discharge, whereas argon plasma alone was practically
      not sufficient in biofilm removal. The impact of plasma etching on biofilms is
      localized due to the limited presence of reactive plasma species validated by
      optical emission spectroscopy.

PMID- 22880026
TI  - USP22 is useful as a novel molecular marker for predicting disease progression
      and patient prognosis of oral squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVE: The significance of ubiquitin-specific protease 22
      (USP22) as a potential marker has been growing in the field of oncology. The aim
      of this study was to investigate the role of USP22 and the association with its
      potential targets in oral squamous cell carcinoma (OSCC). METHODS:
      Immunohistochemistry was used to determine the expression of USP22 protein in 319
      OSCC patients in comparison with 42 healthy controls. The clinical correlations
      and prognostic significance of the aberrantly expressed protein was evaluated to
      identify novel biomarker of OSCC. RESULTS: The incidence of positive USP22
      expression was 63.32% in 319 conventional OSCC tissues. The protein expression
      level of USP22 was concomitantly up-regulated from non-cancerous mucosa to
      primary carcinoma and from carcinomas to lymph node metastasis (P<0.001).
      Moreover, statistical analysis showed that positive USP22 expression was
      positively related to lymph node metastasis, Ki67, Cox-2 and recurrence.
      Furthermore, it was shown that patients with positive USP22 expression had
      significantly poorer outcome compared with patients with negative expression of
      USP22 for patients with positive lymph nodes. Multivariate Cox regression
      analysis revealed that USP22 expression level was an independent prognostic
      factor for both overall survival and disease-free survival (P<0.001 and P<0.001,
      respectively). Cancer cells with reduced USP22 expression exhibited reduced
      proliferation and colony formation evaluated by MTT and soft agar assays.
      CONCLUSION: To our knowledge, this is the first study that determines the
      relationship between USP22 expression and prognosis in OSCC. We found that
      increased expression of USP22 is associated with poor prognosis in OSCC. USP22
      may represent a novel and useful prognostic marker for OSCC.

PMID- 22880027
TI  - MicroRNA-30b-mediated regulation of catalase expression in human ARPE-19 cells.
AB  - BACKGROUND: Oxidative injury to retinal pigment epithelium (RPE) and retinal
      photoreceptors has been linked to a number of retinal diseases, including age
      related macular degeneration (AMD). Reactive oxygen species (ROS)-mediated gene
      expression has been extensively studied at transcriptional levels. Also, the post
      transcriptional control of gene expression at the level of translational
      regulation has been recently reported. However, the microRNA (miRNA/miR)-mediated
      post-transcriptional regulation in human RPE cells has not been thoroughly looked
      at. Increasing evidence points to a potential role of miRNAs in diverse
      physiological processes. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated for the
      first time in a human retinal pigment epithelial cell line (ARPE-19) that the
      post-transcriptional control of gene expression via miRNA modulation regulates
      human catalase, an important and potent component of cell's antioxidant defensive
      network, which detoxifies hydrogen peroxide (H(2)O(2)) radicals. Exposure to
      several stress-inducing agents including H(2)O(2) has been reported to alter
      miRNA expression profile. Here, we demonstrated that a sublethal dose of H(2)O(2)
      (200 uM) up-regulated the expression of miR-30b, a member of the miR-30 family,
      which inhibited the expression of endogenous catalase both at the transcript and
      protein levels. However, antisense (antagomirs) of miR-30b was not only found to
      suppress the miR-30b mimics-mediated inhibitions, but also to dramatically
      increase the expression of catalase even under an oxidant environment.
      CONCLUSIONS/SIGNIFICANCE: We propose that a microRNA antisense approach could
      enhance cytoprotective mechanisms against oxidative stress by increasing the
      antioxidant defense system.

PMID- 22880028
TI  - Not all mice are equal: welfare implications of behavioural habituation profiles
      in four 129 mouse substrains.
AB  - Safeguarding the welfare of animals is an important aim when defining housing and
      management standards in animal based, experimental research. While such standards
      are usually defined per animal species, it is known that considerable differences
      between laboratory mouse strains exist, for example with regard to their
      emotional traits. Following earlier experiments, in which we found that 129P3
      mice show a lack of habituation of anxiety related behaviour after repeated
      exposure to an initially novel environment (non-adaptive profile), we here
      investigated four other 129 inbred mouse substrains (129S2/SvPas, 129S2/SvHsd
      (exp 1); 129P2 and 129X1 (exp 2)) on habituation of anxiety related behaviour.
      Male mice of each strain were repeatedly placed in the modified hole board test,
      measuring anxiety-related behaviour, exploratory and locomotor behaviour. The
      results reveal that all four substrains show a lack of habituation behaviour
      throughout the period of testing. Although not in all of the substrains a
      possible confounding effect of general activity can be excluded, our findings
      suggest that the genetic background of the 129 substrains may increase their
      vulnerability to cope with environmental challenges, such as exposure to novelty.
      This vulnerability might negatively affect the welfare of these mice under
      standard laboratory conditions when compared with other strains. Based on our
      findings we suggest to consider (sub)strain-specific guidelines and protocols,
      taking the (subs)train-specific adaptive capabilities into account.

PMID- 22880029
TI  - Single-channel electrophysiology reveals a distinct and uniform pore complex
      formed by alpha-synuclein oligomers in lipid membranes.
AB  - Synucleinopathies such as Parkinson's disease, multiple system atrophy and
      dementia with Lewy bodies are characterized by deposition of aggregated alpha
      synuclein. Recent findings indicate that pathological oligomers rather than
      fibrillar aggregates may represent the main toxic protein species. It has been
      shown that alpha-synuclein oligomers can increase the conductance of lipid
      bilayers and, in cell-culture, lead to calcium dyshomeostasis and cell death. In
      this study, employing a setup for single-channel electrophysiology, we found that
      addition of iron-induced alpha-synuclein oligomers resulted in quantized and
      stepwise increases in bilayer conductance indicating insertion of distinct
      transmembrane pores. These pores switched between open and closed states
      depending on clamped voltage revealing a single-pore conductance comparable to
      that of bacterial porins. Pore conductance was dependent on transmembrane
      potential and the available cation. The pores stably inserted into the bilayer
      and could not be removed by buffer exchange. Pore formation could be inhibited by
      co-incubation with the aggregation inhibitor baicalein. Our findings indicate
      that iron-induced alpha-synuclein oligomers can form a uniform and distinct pore
      species with characteristic electrophysiological properties. Pore formation could
      be a critical event in the pathogenesis of synucleinopathies and provide a novel
      structural target for disease-modifying therapy.

PMID- 22880030
TI  - Galectin-10, a potential biomarker of eosinophilic airway inflammation.
AB  - Measurement of eosinophilic airway inflammation can assist in the diagnosis of
      allergic asthma and in the management of exacerbations, however its clinical
      implementation remains difficult. Galectin-10 has been associated with
      eosinophilic inflammation and has the potential to be used as a surrogate
      biomarker. This study aimed to assess the relationship between galectin-10 in
      sputum with sputum eosinophil counts, the current gold standard of eosinophil
      inflammation in the lung. Thirty-eight sputum samples were processed for both
      eosinophil counts by cytospins and semi-quantitative measurements of galectin-10
      by western blots. A strong association was observed between galectin-10 levels in
      sputum and sputum eosinophil measurements, and they accurately determined sputum
      eosinophilia. The results support the potential for galectin-10 to be used as a
      surrogate biomarker of eosinophilic airway inflammation.

PMID- 22880031
TI  - Peptidome analysis of cerebrospinal fluid by LC-MALDI MS.
AB  - We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by
      mass spectrometry. A method was developed for preparation of peptide extracts
      from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the
      detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were
      identified by MS/MS. The majority of these peptides have not been previously
      reported in CSF. The identified peptides were found to originate from 104
      proteins, of which several have been reported to be involved in different
      disorders of the central nervous system. These results support the notion that
      CSF peptidomics may be viable complement to proteomics in the search of
      biomarkers of CNS disorders.

PMID- 22880032
TI  - Nitric oxide has differential effects on currents in different subsets of Manduca
      sexta antennal lobe neurons.
AB  - Nitric oxide has been shown to regulate many biological systems including
      olfaction. In the moth olfactory system nitric oxide is produced in the antennal
      lobe in response to odor stimulation and has complex effects on the activity of
      both projection neurons and local interneurons. To examine the cell autonomous
      effects of nitric oxide on these cells, we used patch-clamp recording in
      conjunction with pharmacological manipulation of nitric oxide to test the
      hypothesis that nitric oxide differentially regulates the channel properties of
      these different antennal lobe neuron subsets. We found that nitric oxide caused
      increasing inward currents in a subset of projection neurons while the effects on
      local neurons were variable but consistent within identifiable morphological
      subtypes.

PMID- 22880033
TI  - The two PPX-GppA homologues from Mycobacterium tuberculosis have distinct
      biochemical activities.
AB  - Inorganic polyphosphate (poly-P), guanosine pentaphosphate (pppGpp) and guanosine
      tetraphosphate (ppGpp) are ubiquitous in bacteria. These molecules play a variety
      of important physiological roles associated with stress resistance, persistence,
      and virulence. In the bacterial pathogen Mycobacterium tuberculosis, the
      identities of the proteins responsible for the metabolism of polyphosphate and
      (p)ppGpp remain to be fully established. M. tuberculosis encodes two PPX-GppA
      homologues, Rv0496 (MTB-PPX1) and Rv1026, which share significant sequence
      similarity with bacterial exopolyphosphatase (PPX) and guanosine pentaphosphate
      5'-phosphohydrolase (GPP) proteins. Here we delineate the respective biochemical
      activities of the Rv0496 and Rv1026 proteins and benchmark these against the
      activities of the PPX and GPP proteins from Escherichia coli. We demonstrate that
      Rv0496 functions as an exopolyphosphatase, showing a distinct preference for
      relatively short-chain poly-P substrates. In contrast, Rv1026 has no detectable
      exopolyphosphatase activities. Analogous to the E. coli PPX and GPP enzymes, the
      exopolyphosphatase activities of Rv0496 are inhibited by pppGpp and, to a lesser
      extent, by ppGpp alarmones, which are produced during the bacterial stringent
      response. However, neither Rv0496 nor Rv1026 have the ability to hydrolyze pppGpp
      to ppGpp; a reaction catalyzed by E. coli PPX and GPP. Both the Rv0496 and Rv1026
      proteins have modest ATPase and to a lesser extent ADPase activities. pppGpp
      alarmones inhibit the ATPase activities of Rv1026 and, to a lesser extent, the
      ATPase activities of Rv0496. We conclude that PPX-GppA family proteins may not
      possess all the catalytic activities implied by their name and may play distinct
      biochemical roles involved in polyphosphate and (p)ppGpp metabolic pathways.

PMID- 22880034
TI  - Identification of CD166 as a surface marker for enriching prostate
      stem/progenitor and cancer initiating cells.
AB  - New therapies for late stage and castration resistant prostate cancer (CRPC)
      depend on defining unique properties and pathways of cell sub-populations capable
      of sustaining the net growth of the cancer. One of the best enrichment schemes
      for isolating the putative stem/progenitor cell from the murine prostate gland is
      Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold
      enrichment for in vitro sphere-forming activity. We have shown previously that
      the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation
      in the Pten-null prostate cancer model. To further improve this enrichment
      scheme, we searched for cell surface molecules upregulated upon castration of
      murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell
      surface molecule that can further enrich sphere-forming activity of WT LSC(hi)
      and Pten null LSC(hi). Importantly, CD166 could enrich sphere-forming ability of
      benign primary human prostate cells in vitro and induce the formation of tubule
      like structures in vivo. CD166 expression is upregulated in human prostate
      cancers, especially CRPC samples. Although genetic deletion of murine CD166 in
      the Pten null prostate cancer model does not interfere with sphere formation or
      block prostate cancer progression and CRPC development, the presence of CD166 on
      prostate stem/progenitors and castration resistant sub-populations suggest that
      it is a cell surface molecule with the potential for targeted delivery of human
      prostate cancer therapeutics.

PMID- 22880035
TI  - Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB
      N mice and C57BL6 procollagen alpha1(I)-promoter-GFP reporter mice.
AB  - BACKGROUND: Injury and intestinal inflammation trigger wound healing responses
      that can restore mucosal architecture but if chronic, can promote intestinal
      fibrosis. Intestinal fibrosis is a major complication of Crohn's disease. The
      cellular and molecular basis of mucosal healing and intestinal fibrosis are not
      well defined and better understanding requires well characterized mouse models.
      METHODS: FVB-N wild type mice and C57BL6 procollagen alpha1(I)-GFP reporter mice
      were given one (DSS1) or two (DSS2) cycles of 3% DSS (5 days/cycle) followed by 7
      days recovery. Histological scoring of inflammation and fibrosis were performed
      at DSS1, DSS1+3, DSS1+7, DSS2, DSS2+3, and DSS2+7. Procollagen alpha1(I)-GFP
      activation was assessed in DSS and also TNBS models by whole colon GFP imaging
      and fluorescence microscopy. Colocalization of GFP with alpha-smooth muscle actin
      (alpha-SMA) or vimentin was examined. GFP mRNA levels were tested for correlation
      with endogenous collagen alpha1(I) mRNA. RESULTS: Males were more susceptible to
      DSS-induced disease and mortality than females. In FVB-N mice one DSS cycle
      induced transient mucosal inflammation and fibrosis that resolved by 7 days of
      recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset
      of FVB-N mice but overall, did not yield more consistent, severe or sustained
      fibrosis. In C57BL6 mice, procollagen alpha1(I)-GFP reporter was activated at the
      end of DSS1 and through DSS+7 with more dramatic and transmural activation at
      DSS2 through DSS2+7, and in TNBS treated mice. In DSS and TNBS models GFP
      reporter expression localized to vimentin(+) cells and much fewer alpha-SMA(+)
      cells. GFP mRNA strongly correlated with collagen alpha1(I) mRNA. CONCLUSIONS:
      One DSS cycle in FVB-N mice provides a model to study mucosal injury and
      subsequent mucosal healing. The procollagen alpha1(I)-GFP transgenic provides a
      useful model to study activation of a gene encoding a major extracellular matrix
      protein during acute or chronic experimental intestinal inflammation and
      fibrosis.

PMID- 22880036
TI  - Successful development of small diameter tissue-engineering vascular vessels by
      our novel integrally designed pulsatile perfusion-based bioreactor.
AB  - Small-diameter (<4 mm) vascular constructs are urgently needed for patients
      requiring replacement of their peripheral vessels. However, successful
      development of constructs remains a significant challenge. In this study, we
      successfully developed small-diameter vascular constructs with high patency using
      our integrally designed computer-controlled bioreactor system. This computer
      controlled bioreactor system can confer physiological mechanical stimuli and
      fluid flow similar to physiological stimuli to the cultured grafts. The medium
      circulating system optimizes the culture conditions by maintaining fixed
      concentration of O(2) and CO(2) in the medium flow and constant delivery of
      nutrients and waste metabolites, as well as eliminates the complicated
      replacement of culture medium in traditional vascular tissue engineering.
      Biochemical and mechanical assay of newly developed grafts confirm the
      feasibility of the bioreactor system for small-diameter vascular engineering.
      Furthermore, the computer-controlled bioreactor is superior for cultured cell
      proliferation compared with the traditional non-computer-controlled bioreactor.
      Specifically, our novel bioreactor system may be a potential alternative for
      tissue engineering of large-scale small-diameter vascular vessels for clinical
      use.

PMID- 22880038
TI  - Anthropogenic influences on macro-level mammal occupancy in the Appalachian Trail
      corridor.
AB  - Anthropogenic effects on wildlife are typically assessed at the local level, but
      it is often difficult to extrapolate to larger spatial extents. Macro-level
      occupancy studies are one way to assess impacts of multiple disturbance factors
      that might vary over different geographic extents. Here we assess anthropogenic
      effects on occupancy and distribution for several mammal species within the
      Appalachian Trail (AT), a forest corridor that extends across a broad section of
      the eastern United States. Utilizing camera traps and a large volunteer network
      of citizen scientists, we were able to sample 447 sites along a 1024 km section
      of the AT to assess the effects of available habitat, hunting, recreation, and
      roads on eight mammal species. Occupancy modeling revealed the importance of
      available forest to all species except opossums (Didelphis virginiana) and
      coyotes (Canis latrans). Hunting on adjoining lands was the second strongest
      predictor of occupancy for three mammal species, negatively influencing black
      bears (Ursus americanus) and bobcats (Lynx rufus), while positively influencing
      raccoons (Procyon lotor). Modeling also indicated an avoidance of high trail use
      areas by bears and proclivity towards high use areas by red fox (Vulpes vulpes).
      Roads had the lowest predictive power on species occupancy within the corridor
      and were only significant for deer. The occupancy models stress the importance of
      compounding direct and indirect anthropogenic influences operating at the
      regional level. Scientists and managers should consider these human impacts and
      their potential combined influence on wildlife persistence when assessing optimal
      habitat or considering management actions.

PMID- 22880037
TI  - Activation of Wnt/beta-catenin signalling affects differentiation of cells
      arising from the cerebellar ventricular zone.
AB  - Development of the cerebellum proceeds under the precise spatio-temporal control
      of several key developmental signalling pathways, including the Wnt/beta-catenin
      pathway. We recently reported the activity of Wnt/beta-catenin signalling in the
      perinatal cerebellar ventricular zone (VZ), a germinal centre in the developing
      cerebellum that gives rise to GABAergic and glial cells. In order to investigate
      the normal function of Wnt/beta-catenin signalling in the VZ and the cell
      lineages it gives rise to, we used a combination of ex vivo cerebellar slice
      culture and in vivo genetic manipulation to dysregulate its activity during late
      embryonic development. Activation of the pathway at the cerebellar ventricular
      zone led to a reduction in the number of cells expressing the glial lineage
      markers Sox9 and GFAP and the interneuron marker Pax2, but had no consistent
      effect on either proliferation or apoptosis. Our findings suggest that activation
      of the Wnt/beta-catenin pathway in the cerebellar ventricular zone causes a shift
      in the cell types produced, most likely due to disruption of normal
      differentiation. Thus, we propose that regulation of Wnt/beta-catenin signalling
      levels are required for normal development of cells arising from the cerebellar
      ventricular zone during late embryogenesis.

PMID- 22880039
TI  - 'Leaves and eats shoots': direct terrestrial feeding can supplement invasive red
      swamp crayfish in times of need.
AB  - We used stable isotope analyses to characterise the feeding dynamics of a
      population of red swamp crayfish in Lake Naivasha, Kenya, after the crash of
      submerged macrophytes and associated macroinvertebrates, and during a natural
      draw-down of the lake water level. We expected a heavy reliance upon a diet of
      detrital matter to sustain the population as a consequence, and indeed, for the
      majority of the crayfish population caught from the lake, we saw a concomitant
      shift in isotopic values reflecting a dietary change. However, we also caught
      individual crayfish that had occupied the footprints of hippopotamus and
      effectively extended their range beyond the lake up to 40 m into the riparian
      zone. Isotopic analysis confirmed limited nocturnal observations that these
      individuals were consuming living terrestrial plants in the vicinity of the
      footprints. These are the first empirical data to demonstrate direct use of
      terrestrial resources by an aquatic crayfish species and further highlight the
      traits that make red swamp crayfish such opportunistic and successful invaders.

PMID- 22880040
TI  - FT-ICR/MS and GC-EI/MS metabolomics networking unravels global potato sprout's
      responses to Rhizoctonia solani infection.
AB  - The complexity of plant-pathogen interactions makes their dissection a
      challenging task for metabolomics studies. Here we are reporting on an integrated
      metabolomics networking approach combining gas chromatography/mass spectrometry
      (GC/MS) with Fourier transform ion cyclotron resonance/mass spectrometry (FT
      ICR/MS) and bioinformatics analyses for the study of interactions in the potato
      sprout-Rhizoctonia solani pathosystem and the fluctuations in the global
      metabolome of sprouts. The developed bioanalytical and bioinformatics protocols
      provided a snapshot of the sprout's global metabolic network and its
      perturbations as a result of pathogen invasion. Mevalonic acid and deoxy-xylulose
      pathways were substantially up-regulated leading to the biosynthesis of
      sesquiterpene alkaloids such as the phytoalexins phytuberin, rishitin, and
      solavetivone, and steroidal alkaloids having solasodine and solanidine as their
      common aglycons. Additionally, the perturbation of the sprout's metabolism was
      depicted in fluctuations of the content of their amino acids pool and that of
      carboxylic and fatty acids. Components of the systemic acquired resistance (SAR)
      and hypersensitive reaction (HR) such as azelaic and oxalic acids were detected
      in increased levels in infected sprouts and strategies of the pathogen to
      overcome plant defense were proposed. Our metabolic approach has not only greatly
      expanded the multitude of metabolites previously reported in potato in response
      to pathogen invasion, but also enabled the identification of bioactive plant
      derived metabolites providing valuable information that could be exploited in
      biotechnology, biomarker-assisted plant breeding, and crop protection for the
      development of new crop protection agents.

PMID- 22880041
TI  - Activation of endogenous FAK via expression of its amino terminal domain in
      Xenopus embryos.
AB  - BACKGROUND: The Focal Adhesion Kinase is a well studied tyrosine kinase involved
      in a wide number of cellular processes including cell adhesion and migration. It
      has also been shown to play important roles during embryonic development and
      targeted disruption of the FAK gene in mice results in embryonic lethality by day
      8.5. PRINCIPAL FINDINGS: Here we examined the pattern of phosphorylation of FAK
      during Xenopus development and found that FAK is phosphorylated on all major
      tyrosine residues examined from early blastula stages well before any
      morphogenetic movements take place. We go on to show that FRNK fails to act as a
      dominant negative in the context of the early embryo and that the FERM domain has
      a major role in determining FAK's localization at the plasma membrane. Finally,
      we show that autonomous expression of the FERM domain leads to the activation of
      endogenous FAK in a tyrosine 397 dependent fashion. CONCLUSIONS: Overall, our
      data suggest an important role for the FERM domain in the activation of FAK and
      indicate that integrin signalling plays a limited role in the in vivo activation
      of FAK at least during the early stages of development.

PMID- 22880042
TI  - HIV-1 envelope resistance to proteasomal cleavage: implications for vaccine
      induced immune responses.
AB  - BACKGROUND: Antigen processing involves many proteolytic enzymes such as
      proteasomes and cathepsins. The processed antigen is then presented on the cell
      surface bound to either MHC class I or class II molecules and induces/interacts
      with antigen-specific CD8+ and CD4+ T-cells, respectively. Preliminary
      immunological data from the RV144 phase III trial indicated that the immune
      responses were biased towards the Env antigen with a dominant CD4+ T-cell
      response. METHODS: In this study, we examined the susceptibility of HIV-1 Env
      A244 gp120 protein, one of the protein boost subunits of the RV144 Phase III
      vaccine trial, to proteasomes and cathepsins and identified the generated peptide
      epitope repertoire by mass spectrometry. The peptide fragments were tested for
      cytokine production in CD4(+) T-cell lines derived from RV144 volunteers.
      RESULTS: Env-A244 was resistant to proteasomes, thus diminishing the possibility
      of the generation of class I epitopes by the classical MHC class I pathway.
      However, Env-A244 was efficiently cleaved by cathepsins generating peptide arrays
      identified by mass spectrometry that contained both MHC class I and class II
      epitopes as reported in the Los Alamos database. Each of the cathepsins generated
      distinct degradation patterns containing regions of light and dense epitope
      clusters. The sequence DKKQKVHALF that is part of the V2 loop of gp120 produced
      by cathepsins induced a polyfunctional cytokine response including the generation
      of IFN-gamma from CD4(+) T-cell lines-derived from RV144 vaccinees. This sequence
      is significant since antibodies to the V1/V2-loop region correlated inversely
      with HIV-1 infection in the RV144 trial. CONCLUSIONS: Based on our results, the
      susceptibility of Env-A244 to cathepsins and not to proteasomes suggests a
      possible mechanism for the generation of Env-specific CD4(+)T cell and antibody
      responses in the RV144 vaccinees.

PMID- 22880043
TI  - Holistic gaze strategy to categorize facial expression of varying intensities.
AB  - Using faces representing exaggerated emotional expressions, recent behaviour and
      eye-tracking studies have suggested a dominant role of individual facial features
      in transmitting diagnostic cues for decoding facial expressions. Considering that
      in everyday life we frequently view low-intensity expressive faces in which local
      facial cues are more ambiguous, we probably need to combine expressive cues from
      more than one facial feature to reliably decode naturalistic facial affects. In
      this study we applied a morphing technique to systematically vary intensities of
      six basic facial expressions of emotion, and employed a self-paced expression
      categorization task to measure participants' categorization performance and
      associated gaze patterns. The analysis of pooled data from all expressions showed
      that increasing expression intensity would improve categorization accuracy,
      shorten reaction time and reduce number of fixations directed at faces. The
      proportion of fixations and viewing time directed at internal facial features
      (eyes, nose and mouth region), however, was not affected by varying levels of
      intensity. Further comparison between individual facial expressions revealed that
      although proportional gaze allocation at individual facial features was
      quantitatively modulated by the viewed expressions, the overall gaze distribution
      in face viewing was qualitatively similar across different facial expressions and
      different intensities. It seems that we adopt a holistic viewing strategy to
      extract expressive cues from all internal facial features in processing of
      naturalistic facial expressions.

PMID- 22880044
TI  - Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti
      oxidative enzymes and anti-apoptotic genes.
AB  - BACKGROUND: Thymosin beta-4 (Tbeta4) is a ubiquitous protein with many properties
      relating to cell proliferation and differentiation that promotes wound healing
      and modulates inflammatory mediators. The mechanism by which Tbeta4 modulates
      cardiac protection under oxidative stress is not known. The purpose of this study
      is to dissect the cardioprotective mechanism of Tbeta4 on H(2)O(2) induced
      cardiac damage. METHODS: Rat neonatal cardiomyocytes with or without Tbeta4
      pretreatment were exposed to H(2)O(2) and expression of antioxidant, apoptotic,
      and anti-inflammatory genes was evaluated by quantitative real-time PCR and
      western blotting. ROS levels were estimated by DCF-DA using fluorescent
      microscopy and fluorimetry. Selected antioxidant, anti-inflammatory and
      antiapoptotic genes were silenced by siRNA transfections in neonatal
      cardiomyocytes and effect of Tbeta4 on H(2)O(2)-induced cardiac damage was
      evaluated. RESULTS: Pre-treatment of Tbeta4 resulted in reduction of the
      intracellular ROS levels induced by H(2)O(2) in cardiomyocytes. Tbeta4
      pretreatment also resulted in an increase in the expression of antiapoptotic
      proteins and reduction of Bax/BCl(2) ratio in the cardiomyocytes. Pretreatment
      with Tbeta4 resulted in stimulating the expression of antioxidant enzymes
      copper/zinc SOD and catalase in cardiomyocytes at both transcription and
      translation levels. Tbeta4 treatment resulted in the increased expression of anti
      apoptotic and anti-inflammatory genes. Silencing of Cu/Zn SOD and catalase gene
      resulted in apoptotic cell death in the cardiomyocytes which was prevented by
      treatment with Tbeta4. CONCLUSION: This is the first report that demonstrates the
      effect of Tbeta4 on cardiomyocytes and its capability to selectively upregulate
      anti-oxidative enzymes, anti-inflammatory genes, and antiapoptotic enzymes in the
      neonatal cardiomyocytes thus preventing cell death thereby protecting the
      myocardium. Tbeta4 treatment resulted in decreased oxidative stress and
      inflammation in the myocardium under oxidative stress.

PMID- 22880045
TI  - Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in
      vivo PET assays of rat brain.
AB  - A novel investigational antidepressant with high affinity for the serotonin
      transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural
      formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4
      oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been
      found to exert a rapid therapeutic effect, although the mechanistic basis for
      this potential advantage remains undetermined. We comparatively investigated the
      pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission
      tomographic (PET) and autoradiographic assays of rat brains in order to elucidate
      their molecular interactions with presynaptic and postsynaptic 5-HT(1A)
      receptors. In contrast to the full receptor occupancy by pindolol in PET
      measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited
      capacity, with relatively high receptor occupancy being achieved in regions
      predominantly containing presynaptic receptors. This selectivity was further
      proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5
      HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[gamma-thio]triphosphate
      autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A)
      receptors. This finding has lent support to reports that diverse partial agonists
      for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus,
      the present PET data suggest a relatively high capacity of presynaptic binding
      sites for partial agonists. Since our in vitro and ex vivo autoradiographies
      failed to illustrate these distinct features of Wf-516, in vivo PET imaging is
      considered to be, thus far, the sole method capable of pharmacokinetically
      demonstrating the unique actions of Wf-516 and similar new-generation
      antidepressants.

PMID- 22880046
TI  - Association of serum bilirubin with contrast-induced nephropathy and future
      cardiovascular events in patients undergoing coronary intervention.
AB  - OBJECTIVES: Enhanced reactive oxygen species formation within the kidney
      following the administration of contrast media may play a key role in the
      development of contrast-induced nephropathy (CIN). Bilirubin has emerged as an
      important endogenous antioxidant molecule. This study was undertaken to determine
      whether bilirubin is associated with CIN and future cardiovascular events in
      patients undergoing coronary intervention. METHODS: Totally, 544 consecutive
      patients received coronary intervention were enrolled. All patients were followed
      up for at least 3 years or until the occurrence of a major event. The primary
      endpoint was CIN, defined as a rise in serum creatinine (SCr) of 0.5 mg/dl or a
      25% increase from the baseline value within 48 hours after the procedure. The
      secondary endpoint was the combined occurrence of major adverse cardiovascular
      events (MACE), including death, nonfatal myocardial infarction, and ischemic
      stroke. RESULTS: Overall, CIN occurred in 85 (15.6%) patients. All patients were
      stratified into 3 groups (low/normal/high) according to the serum bilirubin
      levels. In a multivariate logistic analysis, the odds ratio for CIN with low
      bilirubin levels relative to high-bilirubin levels was 11.82 (95% CI, 3.25
      43.03). By Cox regression analysis, serum bilirubin levels was an independent
      predictor of MACE in patients undergoing coronary intervention (low vs. high
      hazard ratio 2.26; 95% CI, 1.05-4.90). CONCLUSIONS: CIN is a serious complication
      of coronary intervention. Higher serum bilirubin concentrations were associated
      with lower risk of CIN and fewer cardiovascular events. The development of
      interventions that promote bilirubin levels may be a potential target to reduce
      CIN and future MACE in patients undergoing coronary intervention.

PMID- 22880047
TI  - MMP-13 regulates growth of wound granulation tissue and modulates gene expression
      signatures involved in inflammation, proteolysis, and cell viability.
AB  - Proteinases play a pivotal role in wound healing by regulating cell-matrix
      interactions and availability of bioactive molecules. The role of matrix
      metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in
      subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/-))
      and wild type (WT) mice. The tissue samples were harvested at time points day 7,
      14 and 21 and subjected to histological analysis and gene expression profiling.
      Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13(-/-)
      mice. Granulation tissue in Mmp13(-/-) mice showed delayed organization of
      myofibroblasts, increased microvascular density at day 14, and virtual absence of
      large vessels at day 21. Gene expression profiling identified differentially
      expressed genes in Mmp13(-/-) mouse granulation tissue involved in biological
      functions including inflammatory response, angiogenesis, cellular movement,
      cellular growth and proliferation and proteolysis. Among genes linked to
      angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation
      tissue in Mmp13(-/-) mice, and a set of genes involved in leukocyte motility
      including Il6 were systematically downregulated at day 14. The expression of
      Pdgfd was downregulated in Mmp13(-/-) granulation tissue in all time points. The
      expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly
      downregulated in granulation tissue of Mmp13(-/-) mice compared to WT mice.
      Mmp13(-/-) mouse skin fibroblasts displayed altered cell morphology and impaired
      ability to contract collagen gel and decreased production of MMP-2. These results
      provide evidence for an important role for MMP-13 in wound healing by
      coordinating cellular activities important in the growth and maturation of
      granulation tissue, including myofibroblast function, inflammation, angiogenesis,
      and proteolysis.

PMID- 22880048
TI  - BRAFV600E negatively regulates the AKT pathway in melanoma cell lines.
AB  - Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance
      mechanism for cancer therapeutic agents targeting either RAF/MEK or
      PI3K/AKT/mTOR. It is thus important to have a better understanding of the
      molecular resistance mechanisms to improve patient survival benefit from these
      agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway.
      Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor
      (RG7167) or mTORC1 inhibitor (rapamycin) induced AKT phosphorylation (pAKT) and
      downstream signal activation. Treatment-induced pAKT elevation is found in BRAF
      wild type melanoma cells but not in a subset of melanoma cell lines harboring
      BRAFV600E. Knock-down of BRAFV600E in these melanoma cells elevates basal pAKT
      and downstream signals, whereas knock-down of CRAF, MEK1/2 or ERK1/2 or treatment
      with a BRAF inhibitor have no impact on pAKT. Mechanistically, we show that
      BRAFV600E interacts with rictor complex (mTORC2) and regulates pAKT through
      mTORC2. BRAFV600E is identified in mTORC2 after immunoprecipitation of rictor.
      Knock-down of rictor abrogates BRAFV600E depletion induced pAKT. Knock-down of
      BRAFV600E enhances cellular enzyme activity of mTORC2. Aberrant activation of AKT
      pathway by PTEN loss appears to override the negative impact of BRAFV600E on
      pAKT. Taken together, our findings suggest that in a subset of BRAFV600E melanoma
      cells, BRAFV600E negatively regulates AKT pathway in a rictor-dependent, MEK/ERK
      and BRAF kinase-independent manner. Our study reveals a novel molecular mechanism
      underlying the regulation of feedback loops between the MAPK and AKT pathways.

PMID- 22880049
TI  - Risk factors for campylobacteriosis of chicken, ruminant, and environmental
      origin: a combined case-control and source attribution analysis.
AB  - BACKGROUND: Campylobacteriosis contributes strongly to the disease burden of food
      borne pathogens. Case-control studies are limited in attributing human infections
      to the different reservoirs because they can only trace back to the points of
      exposure, which may not point to the original reservoirs because of cross
      contamination. Human Campylobacter infections can be attributed to specific
      reservoirs by estimating the extent of subtype sharing between strains from
      humans and reservoirs using multilocus sequence typing (MLST).
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated risk factors for human
      campylobacteriosis caused by Campylobacter strains attributed to different
      reservoirs. Sequence types (STs) were determined for 696 C. jejuni and 41 C. coli
      strains from endemic human cases included in a case-control study. The asymmetric
      island model, a population genetics approach for modeling Campylobacter evolution
      and transmission, attributed these cases to four putative animal reservoirs
      (chicken, cattle, sheep, pig) and to the environment (water, sand, wild birds)
      considered as a proxy for other unidentified reservoirs. Most cases were
      attributed to chicken (66%) and cattle (21%), identified as the main reservoirs
      in The Netherlands. Consuming chicken was a risk factor for campylobacteriosis
      caused by chicken-associated STs, whereas consuming beef and pork were
      protective. Risk factors for campylobacteriosis caused by ruminant-associated STs
      were contact with animals, barbecuing in non-urban areas, consumption of tripe,
      and never/seldom chicken consumption. Consuming game and swimming in a domestic
      swimming pool during springtime were risk factors for campylobacteriosis caused
      by environment-associated STs. Infections with chicken- and ruminant-associated
      STs were only partially explained by food-borne transmission; direct contact and
      environmental pathways were also important. CONCLUSION/SIGNIFICANCE: This is the
      first case-control study in which risk factors for campylobacteriosis are
      investigated in relation to the attributed reservoirs based on MLST profiles.
      Combining epidemiological and source attribution data improved campylobacteriosis
      risk factor identification and characterization, generated hypotheses, and showed
      that genotype-based source attribution is epidemiologically sensible.

PMID- 22880050
TI  - Characterization of Na+ and Ca2+ channels in zebrafish dorsal root ganglion
      neurons.
AB  - BACKGROUND: Dorsal root ganglia (DRG) somata from rodents have provided an
      excellent model system to study ion channel properties and modulation using
      electrophysiological investigation. As in other vertebrates, zebrafish (Danio
      rerio) DRG are organized segmentally and possess peripheral axons that bifurcate
      into each body segment. However, the electrical properties of zebrafish DRG
      sensory neurons, as compared with their mammalian counterparts, are relatively
      unexplored because a preparation suitable for electrophysiological studies has
      not been available. METHODOLOGY/PRINCIPAL FINDINGS: We show enzymatically
      dissociated DRG neurons from juvenile zebrafish expressing Isl2b-promoter driven
      EGFP were easily identified with fluorescence microscopy and amenable to
      conventional whole-cell patch-clamp studies. Two kinetically distinct TTX
      sensitive Na(+) currents (rapidly- and slowly-inactivating) were discovered.
      Rapidly-inactivating I(Na) were preferentially expressed in relatively large
      neurons, while slowly-inactivating I(Na) was more prevalent in smaller DRG
      neurons. RT-PCR analysis suggests zscn1aa/ab, zscn8aa/ab, zscn4ab and zscn5Laa
      are possible candidates for these I(Na) components. Voltage-gated Ca(2+) currents
      (I(Ca)) were primarily (87%) comprised of a high-voltage activated component
      arising from omega-conotoxin GVIA-sensitive Ca(V)2.2 (N-type) Ca(2+) channels. A
      few DRG neurons (8%) displayed a miniscule low-voltage-activated component. I(Ca)
      in zebrafish DRG neurons were modulated by neurotransmitters via either voltage
      dependent or -independent G-protein signaling pathway with large cell-to-cell
      response variability. CONCLUSIONS/SIGNIFICANCE: Our present results indicate
      that, as in higher vertebrates, zebrafish DRG neurons are heterogeneous being
      composed of functionally distinct subpopulations that may correlate with
      different sensory modalities. These findings provide the first comparison of
      zebrafish and rodent DRG neuron electrical properties and thus provide a basis
      for future studies.

PMID- 22880051
TI  - Leaf area and water content changes after permanent and temporary storage.
AB  - Accurate measurements of leaf morphology must be taken to develop models of
      ecosystem productivity and climate change projections. Once leaves are removed
      from a plant they begin to lose water and degrade. If specimens cannot be
      measured immediately after harvest, it is important to store the leaves in a
      manner that reduces morphological changes. If preserved specimens are used,
      estimates that closely match fresh measurements need to be calculated. This study
      examined the change in leaf area after storage treatments and developed models
      that can be used to more accurately estimate initial leaf area. Fresh leaf area
      was measured from ten plant species then stored in one of two common storage
      treatments. After storage, leaf area was re-measured and comparisons were made
      between species and growth forms. Leaf area decreased the most after permanent
      storage treatments and the least after temporary storage. Pressed leaves shrunk
      over 18% while cold storage leaves shrunk under 4%. The woody dicot growth form
      shrunk the least in all treatments. Shrinkage was positively correlated with
      initial water content and dissection index, a measure of leaf shape and
      complexity.

PMID- 22880052
TI  - Cancer incidence among adolescents and young adults in urban Shanghai, 1973-2005.
AB  - BACKGROUND: Lack of cancer incidence information for adolescents and young adults
      led us to describe incidence trends within the young population of 15 to 49 year
      olds in urban Shanghai between 1973 and 2005. METHODS: During 1973 to 2005, data
      on 43,009 (45.8%) male and 50,828 (54.2%) female cancer cases aged 15-49 years
      from the Shanghai Cancer Registry were analyzed. Five-year age-specific rates,
      world age-standardized rates, percent change (PC), and annual percent change
      (APC) were calculated using annual data on population size and its estimated age
      structure. RESULTS: During the 33-year study period, overall cancer incidence of
      adolescents and young adults among males marginally decreased by 0.5% per year
      (P<0.05). However, overall cancer incidence for females slightly increased by
      0.8% per year (P<0.05). The leading cancer for males in rank were liver, stomach,
      lung, colorectal, and nasopharyngeal cancers and for females were breast,
      stomach, colorectal, thyroid, and ovarian cancers. Among specific sites,
      incidence rates significantly decreased for cancers of the esophagus, stomach,
      and liver in both sexes. In contrast, incidence rates significantly increased for
      kidney cancers, non-Hodgkin lymphoma, and brain and nervous system tumors in both
      sexes and increased for breast and ovarian cancers among females. CONCLUSIONS:
      Overall cancer incidence rates of adolescents and young adults decreased in males
      whereas they increased in females. Our findings suggest the importance of further
      epidemiology and etiologic studies to further elucidate factors contributing to
      the cancer incidence trends of adolescents and young adults in China.

PMID- 22880053
TI  - High-throughput screening and rapid inhibitor triage using an infectious chimeric
      Hepatitis C virus.
AB  - The recent development of a Hepatitis C virus (HCV) infectious virus cell culture
      model system has facilitated the development of whole-virus screening assays
      which can be used to interrogate the entire virus life cycle. Here, we describe
      the development of an HCV growth assay capable of identifying inhibitors against
      all stages of the virus life cycle with assay throughput suitable for rapid
      screening of large-scale chemical libraries. Novel features include, 1) the use
      of an efficiently-spreading, full-length, intergenotypic chimeric reporter virus
      with genotype 1 structural proteins, 2) a homogenous assay format compatible with
      miniaturization and automated liquid-handling, and 3) flexible assay end-points
      using either chemiluminescence (high-throughput screening) or Cellomics
      ArrayScanTM technology (high-content screening). The assay was validated using
      known HCV antivirals and through a large-scale, high-throughput screening
      campaign that identified novel and selective entry, replication and late-stage
      inhibitors. Selection and characterization of resistant viruses provided
      information regarding inhibitor target and mechanism. Leveraging results from
      this robust whole-virus assay represents a critical first step towards
      identifying inhibitors of novel targets to broaden the spectrum of antivirals for
      the treatment of HCV.

PMID- 22880054
TI  - Src kinase and Syk activation initiate PI3K signaling by a chimeric latent
      membrane protein 1 in Epstein-Barr virus (EBV)+ B cell lymphomas.
AB  - The B lymphotrophic gamma-herpesvirus EBV is associated with a variety of
      lymphoid- and epithelial-derived malignancies, including B cell lymphomas in
      immunocompromised and immunosuppressed individuals. The primary oncogene of EBV,
      latent membrane protein 1 (LMP1), activates the PI3K/Akt pathway to induce the
      autocrine growth factor, IL-10, in EBV-infected B cells, but the mechanisms
      underlying PI3K activation remain incompletely understood. Using small molecule
      inhibition and siRNA strategies in human B cell lines expressing a chimeric,
      signaling-inducible LMP1 protein, nerve growth factor receptor (NGFR)-LMP1, we
      show that NGFR-LMP1 utilizes Syk to activate PI3K/Akt signaling and induce IL-10
      production. NGFR-LMP1 signaling induces phosphorylation of BLNK, a marker of Syk
      activation. Whereas Src kinases are often required for Syk activation, we show
      here that PI3K/Akt activation and autocrine IL-10 production by NGFR-LMP1
      involves the Src family kinase Fyn. Finally, we demonstrate that NGFR-LMP1
      induces phosphorylation of c-Cbl in a Syk- and Fyn-dependent fashion. Our results
      indicate that the EBV protein LMP1, which lacks the canonical ITAM required for
      Syk activation, can nevertheless activate Syk, and the Src kinase Fyn, resulting
      in downstream c-Cbl and PI3K/Akt activation. Fyn, Syk, and PI3K/Akt antagonists
      thus may present potential new therapeutic strategies that target the oncogene
      LMP1 for treatment of EBV+ B cell lymphomas.

PMID- 22880055
TI  - Early-life stress is associated with gender-based vulnerability to
      epileptogenesis in rat pups.
AB  - During development, the risk of developing mesial temporal lobe epilepsy (MTLE)
      increases when the developing brain is exposed to more than one insult in early
      life. Early life insults include abnormalities of cortical development, hypoxic
      ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have
      developed a two-hit model of MTLE characterized by two early-life insults: a
      freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a
      prolonged hyperthermic seizure (HS) at P10. As early life stressors lead to
      sexual dimorphism in both acute response and long-term outcome, we hypothesized
      that our model could lead to gender-based differences in acute stress response
      and long-term risk of developing MTLE. Male and female pups underwent a freeze
      lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals
      were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma
      corticosterone levels were used to measure stress response at P1 and P10. To
      confirm the role of sex steroids, androgenized female pups received daily
      testosterone injections to the mother pre-natally and post-natally for nine days
      while undergoing both insults. We demonstrated that after both insults females
      did not develop MTLE while all males did. This correlated with a rise in
      corticosterone levels at P1 following the lesion in males only. Interestingly,
      all androgenized females showed a similar rise in corticosterone at P1, and also
      developed MTLE. Moreover, we found that the cortical lesion significantly
      decreased the latency to generalized convulsion during hyperthermia at P10 in
      both genders. The cortical dysplasia volumes at adulthood were also similar
      between male and female individuals. Our data demonstrate sexual dimorphism in
      long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal
      model of MTLE and suggest that the response to early-life stress at P1
      contributes significantly to epileptogenesis in a gender-specific manner.

PMID- 22880056
TI  - Effective group training for patients with unexplained physical symptoms: a
      randomized controlled trial with a non-randomized one-year follow-up.
AB  - BACKGROUND: Although cognitive-behavioral therapy for Unexplained Physical
      Symptoms (UPS) is effective in secondary care, studies done in primary care
      produced implementation problems and conflicting results. We evaluated the
      effectiveness of a cognitive-behavioral group training tailored to primary care
      patients and provided by a secondary community mental-health service reaching out
      into primary care. METHODOLOGY/PRINCIPAL FINDINGS: The effectiveness of this
      training was explored in a randomized controlled trial. In this trial, 162
      patients with UPS classified as undifferentiated somatoform disorder or as
      chronic pain disorder were randomized either to the training or a waiting list.
      Both lasted 13 weeks. The preservation of the training's effect was analyzed in
      non-randomized follow-ups, for which the waiting group started the training after
      the waiting period. All patients attended the training were followed-up after
      three months and again after one year. The primary outcomes were the physical and
      the mental summary scales of the SF-36. Secondary outcomes were the other SF-36
      scales and the SCL-90-R. The courses of the training's effects in the randomized
      controlled trial and the follow-ups were analyzed with linear mixed modeling. In
      the randomized controlled trial, the training had a significantly positive effect
      on the quality of life in the physical domain (Cohen's d = 0.38;p = .002), but
      this overall effect was not found in the mental domain. Regarding the secondary
      outcomes, the training resulted in reporting an improved physical (Cohen's d =
      0.43;p = 0.01), emotional (Cohen's d = 0.44;p = 0.01), and social (Cohen's d =
      0.36;p = 0.01) functioning, less pain and better functioning despite pain
      (Cohen's d = 0.51;p = <0.001), less physical symptoms (Cohen's d = -.23;p = 0.05)
      and less sleep difficulties (Cohen's d = -0.25;p = 0.04) than time in the waiting
      group. During the non-randomized follow-ups, there were no relapses.
      CONCLUSIONS/SIGNIFICANCE: The cognitive-behavioral group training tailored for
      UPS in primary care and provided by an outreaching secondary mental-health
      service appears to be effective and to broaden the accessibility of treatment for
      UPS. TRIAL REGISTRATION: TrialRegister.nl NTR1609
      <rctview.asp&quest;TC&hairsp;&equals;&hairsp;1609>

PMID- 22880057
TI  - AvrRpm1 missense mutations weakly activate RPS2-mediated immune response in
      Arabidopsis thaliana.
AB  - Plants recognize microbes via specific pattern recognition receptors that are
      activated by microbe-associated molecular patterns (MAMPs), resulting in MAMP
      triggered immunity (MTI). Successful pathogens bypass MTI in genetically diverse
      hosts via deployment of effectors (virulence factors) that inhibit MTI responses,
      leading to pathogen proliferation. Plant pathogenic bacteria like Pseudomonas
      syringae utilize a type III secretion system to deliver effectors into cells.
      These effectors can contribute to pathogen virulence or elicit disease
      resistance, depending upon the host plant genotype. In disease resistant
      genotypes, intracellular immune receptors, typically belonging to the nucleotide
      binding leucine-rich repeat family of proteins, perceive bacterial effector(s)
      and initiate downstream defense responses (effector triggered immunity) that
      include the hypersensitive response, and transcriptional re-programming leading
      to various cellular outputs that collectively halt pathogen growth. Nucleotide
      binding leucine-rich repeat sensors can be indirectly activated via perturbation
      of a host protein acting as an effector target. AvrRpm1 is a P. syringae type III
      effector. Upon secretion into the host cell, AvrRpm1 is acylated by host enzymes
      and directed to the plasma membrane, where it contributes to virulence. This is
      correlated with phosphorylation of Arabidopsis RIN4 in vivo. RIN4 is a negative
      regulator of MAMP-triggered immunity, and its modification in the presence of
      four diverse type III effectors, including AvrRpm1, likely enhances this RIN4
      regulatory function. The RPM1 nucleotide binding leucine-rich repeat sensor
      perceives RIN4 perturbation in disease resistant plants, leading to a successful
      immune response. Here, demonstrate that AvrRpm1 has a fold homologous to the
      catalytic domain of poly(ADP-ribosyl) polymerase. Site-directed mutagenesis of
      each residue in the putative catalytic triad, His63-Tyr122-Asp185 of AvrRpm1,
      results in loss of both AvrRpm1-dependent virulence and AvrRpm1-mediated
      activation of RPM1, but, surprisingly, causes a gain of function: the ability to
      activate the RPS2 nucleotide binding leucine-rich repeat sensor.

PMID- 22880058
TI  - Lysosomal-associated transmembrane protein 5 (LAPTM5) is a molecular partner of
      CD1e.
AB  - The CD1e protein participates in the presentation of lipid antigens in dendritic
      cells. Its transmembrane precursor is transported to lysosomes where it is
      cleaved into an active soluble form. In the presence of bafilomycin, which
      inhibits vacuolar ATPase and consequently the acidification of endosomal
      compartments, CD1e associates with a 27 kD protein. In this work, we identified
      this molecular partner as LAPTM5. The latter protein and CD1e colocalize in trans
      Golgi and late endosomal compartments. The quantity of LAPTM5/CD1e complexes
      increases when the cells are treated with bafilomycin, probably due to the
      protection of LAPTM5 from lysosomal proteases. Moreover, we could demonstrate
      that LAPTM5/CD1e association occurs under physiological conditions. Although
      LAPTM5 was previously shown to act as a platform recruiting ubiquitin ligases and
      facilitating the transport of receptors to lysosomes, we found no evidence that
      LATPM5 controls either CD1e ubiquitination or the generation of soluble lysosomal
      CD1e proteins. Notwithstanding these last observations, the interaction of LAPTM5
      with CD1e and their colocalization in antigen processing compartments both
      suggest that LAPTM5 might influence the role of CD1e in the presentation of lipid
      antigens.

PMID- 22880059
TI  - iNKT cells suppress the CD8+ T cell response to a murine Burkitt's-like B cell
      lymphoma.
AB  - The T cell response to B cell lymphomas differs from the majority of solid tumors
      in that the malignant cells themselves are derived from B lymphocytes, key
      players in immune response. B cell lymphomas are therefore well situated to
      manipulate their surrounding microenvironment to enhance tumor growth and
      minimize anti-tumor T cell responses. We analyzed the effect of T cells on the
      growth of a transplantable B cell lymphoma and found that iNKT cells suppressed
      the anti-tumor CD8(+) T cell response. Lymphoma cells transplanted into syngeneic
      wild type (WT) mice or Jalpha18(-/-) mice that specifically lack iNKT cells grew
      initially at the same rate, but only the mice lacking iNKT cells were able to
      reject the lymphoma. This effect was due to the enhanced activity of tumor
      specific CD8(+) T cells in the absence of iNKT cells, and could be partially
      reversed by reconstitution of iNKT cells in Jalpha 18(-/-) mice. Treatment of
      tumor-bearing WT mice with alpha -galactosyl ceramide, an activating ligand for
      iNKT cells, reduced the number of tumor-specific CD8(+) T cells. In contrast,
      lymphoma growth in CD1d1(-/-) mice that lack both iNKT and type II NKT cells was
      similar to that in WT mice, suggesting that type II NKT cells are required for
      full activation of the anti-tumor immune response. This study reveals a tumor
      promoting role for iNKT cells and suggests their capacity to inhibit the CD8(+) T
      cell response to B cell lymphoma by opposing the effects of type II NKT cells.

PMID- 22880060
TI  - Transcriptome analysis and SSR/SNP markers information of the blunt snout bream
      (Megalobrama amblycephala).
AB  - BACKGROUND: Blunt snout bream (Megalobrama amblycephala) is an herbivorous
      freshwater fish species native to China and has been recognized as a main
      aquaculture species in the Chinese freshwater polyculture system with high
      economic value. Right now, only limited EST resources were available for M.
      amblycephala. Recent advances in large-scale RNA sequencing provide a fast, cost
      effective, and reliable approach to generate large expression datasets for
      functional genomic analysis, which is especially suitable for non-model species
      with un-sequenced genomes. METHODOLOGY AND PRINCIPAL FINDINGS: Using 454
      pyrosequencing, a total of 1,409,706 high quality reads (total length 577 Mbp)
      were generated from the normalized cDNA of pooled M. amblycephala individuals.
      These sequences were assembled into 26,802 contigs and 73,675 singletons. After
      BLAST searches against the NCBI non-redundant (NR) and UniProt databases with an
      arbitrary expectation value of E(-10), over 40,000 unigenes were functionally
      annotated and classified using the FunCat functional annotation scheme. A
      comparative genomics approach revealed a substantial proportion of genes
      expressed in M. amblycephala tanscriptome to be shared across the genomes of
      zebrafish, medaka, tetraodon, fugu, stickleback, human, mouse, and chicken, and
      identified a substantial number of potentially novel M. amblycephala genes. A
      total number of 4,952 SSRs were found and 116 polymorphic loci have been
      characterized. A significant number of SNPs (25,697) and indels (23,287) were
      identified based on specific filter criteria in the M. amblycephala. CONCLUSIONS:
      This study is the first comprehensive transcriptome analysis for a fish species
      belonging to the genus Megalobrama. These large EST resources are expected to be
      valuable for the development of molecular markers, construction of gene-based
      linkage map, and large-scale expression analysis of M. amblycephala, as well as
      comparative genome analysis for the genus Megalobrama fish species. The
      identified SSR and SNP markers will greatly benefit its breeding program and
      whole genome association studies.

PMID- 22880061
TI  - Bovine ncRNAs are abundant, primarily intergenic, conserved and associated with
      regulatory genes.
AB  - It is apparent that non-coding transcripts are a common feature of higher
      organisms and encode uncharacterized layers of genetic regulation and
      information. We used public bovine EST data from many developmental stages and
      tissues, and developed a pipeline for the genome wide identification and
      annotation of non-coding RNAs (ncRNAs). We have predicted 23,060 bovine ncRNAs,
      99% of which are un-annotated, based on known ncRNA databases. Intergenic
      transcripts accounted for the majority (57%) of the predicted ncRNAs and the
      occurrence of ncRNAs and genes were only moderately correlated (r = 0.55, p
      value<2.2e-16). Many of these intergenic non-coding RNAs mapped close to the 3'
      or 5' end of thousands of genes and many of these were transcribed from the
      opposite strand with respect to the closest gene, particularly regulatory-related
      genes. Conservation analyses showed that these ncRNAs were evolutionarily
      conserved, and many intergenic ncRNAs proximate to genes contained sequence
      specific motifs. Correlation analysis of expression between these intergenic
      ncRNAs and protein-coding genes using RNA-seq data from a variety of tissues
      showed significant correlations with many transcripts. These results support the
      hypothesis that ncRNAs are common, transcribed in a regulated fashion and have
      regulatory functions.

PMID- 22880062
TI  - Genome-wide detection of spontaneous chromosomal rearrangements in bacteria.
AB  - Genome rearrangements have important effects on bacterial phenotypes and
      influence the evolution of bacterial genomes. Conventional strategies for
      characterizing rearrangements in bacterial genomes rely on comparisons of
      sequenced genomes from related species. However, the spectra of spontaneous
      rearrangements in supposedly homogenous and clonal bacterial populations are
      still poorly characterized. Here we used 454 pyrosequencing technology and a
      'split mapping' computational method to identify unique junction sequences caused
      by spontaneous genome rearrangements in chemostat cultures of Salmonella enterica
      Var. Typhimurium LT2. We confirmed 22 unique junction sequences with a junction
      microhomology more than 10 bp and this led to an estimation of 51 true junction
      sequences, of which 28, 12 and 11 were likely to be formed by deletion,
      duplication and inversion events, respectively. All experimentally confirmed
      rearrangements had short inverted (inversions) or direct (deletions and
      duplications) homologous repeat sequences at the endpoints. This study
      demonstrates the feasibility of genome wide characterization of spontaneous
      genome rearrangements in bacteria and the very high steady-state frequency (20
      40%) of rearrangements in bacterial populations.

PMID- 22880063
TI  - HvHMA2, a P(1B)-ATPase from barley, is highly conserved among cereals and
      functions in Zn and Cd transport.
AB  - Manipulation of crops to improve their nutritional value (biofortification) and
      optimisation of plants for removal of toxic metals from contaminated soils
      (phytoremediation) are major goals. Identification of membrane transporters with
      roles in zinc and cadmium transport would be useful for both aspects. The P(1B)
      ATPases play important roles in heavy metal allocation and detoxification in
      Arabidopsis and it is now important to elucidate their roles in monocots. We
      identified nine P(1B)-ATPases in barley and this study focuses on the functional
      characterization of HvHMA2, providing evidence for its role in heavy metal
      transport. HvHMA2 was cloned using information from EST analysis and 5' RACE. It
      possesses the conserved aspartate that is phosphorylated during the reaction
      cycle of P-type pumps and has motifs and key residues characteristic of P(1B)
      ATPases, falling into the P(1B-2) subclass. Homologous sequences occur in three
      major sub-families of the Poaceae (Gramineae). Heterologous expression in
      Saccharomyces cerevisiae demonstrates that HvHMA2 functions as a Zn and Cd pump.
      Mutagenesis studies show that proposed cation coordination sites of the P(1B-2)
      pumps are crucial for the metal responses conferred by HvHMA2 in yeast. HvHMA2
      expression suppresses the Zn-deficient phenotype of the Arabidopsis hma2hma4
      mutant indicating that HvHMA2 functions as a Zn pump in planta and could play a
      role in root to shoot Zn transport. When expressed in Arabidopsis, HvHMA2
      localises predominantly to the plasma membrane.

PMID- 22880064
TI  - DYT1 knock-in mice are not sensitized against mitochondrial complex-II
      inhibition.
AB  - DYT1 is caused by a partly penetrant dominant mutation in TOR1A that leads to a
      glutamic acid deletion (DeltaE) in torsinA. Identifying environmental factors
      that modulate disease pathogenesis and penetrance could help design therapeutic
      strategies for dystonia. Several cell-based studies suggest that expression of
      torsinA(DeltaE) increases the susceptibility of neuronal cells to challenges to
      their oxidative/energy metabolism. Based on those reports, we hypothesized that
      mice expressing torsinA(DeltaE) would be more susceptible than control
      littermates to the effects of oxidative stress and ATP deficits caused by
      disruption of the mitochondrial respiratory chain in neurons. To test this
      hypothesis, we administered 20 or 50 mg/kg/day of the irreversible complex-II
      inhibitor 3-nitropropionic acid (3-NP) intraperitoneally for 15 consecutive days
      to young heterozygote DYT1 knock-in (KI) mice and wild type littermates. Repeated
      phenotypic assessments were performed at baseline, during and after the
      injections. Animals were then sacrificed and their brains processed for protein
      analysis. The administration of 20 mg/kg 3-NP led to increased levels of torsinA
      in the striatum, the main target of 3-NP, but did not cause motor dysfunction in
      DYT1 KI or control mice. The administration of 50 mg/kg/day of 3-NP caused the
      death of ~40% of wild type animals. Interestingly, DYT1 KI animals showed
      significantly reduced mortality. Surviving animals exhibited abnormal motor
      behavior during and right after the injection period, but recovered by 4 weeks
      postinjection independent of genotype. In contrast to the findings reported in
      cultured cells, these studies suggest the DYT1 mutation does not sensitize
      central neurons against the toxic effects of oxidative stress and energy
      deficits.

PMID- 22880065
TI  - The colitis-associated transcriptional profile of commensal Bacteroides
      thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) may be caused in part by aberrant
      immune responses to commensal intestinal microbes including the well
      characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta).
      Healthy, germ-free HLA-B27 transgenic (Tg) rats develop chronic colitis when
      colonized with complex gut commensal bacteria whereas non-transgenic (nTg) rats
      remain disease-free. However, the role of B. theta in causing disease in Tg rats
      is unknown nor is much known about how gut microbes respond to host inflammation.
      METHODS: Tg and nTg rats were monoassociated with a human isolate of B. theta.
      Colonic inflammation was assessed by histologic scoring and tissue pro
      inflammatory cytokine measurement. Whole genome transcriptional profiling of B.
      theta recovered from ceca was performed using custom GeneChips and data analyzed
      using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment
      Analysis (GSEA) software. Western Blots were used to determine adaptive immune
      responses to a differentially expressed B. theta gene. RESULTS: B. theta
      monoassociated Tg rats, but not nTg or germ-free controls, developed chronic
      colitis. Transcriptional profiles of cecal B. theta were significantly different
      in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved
      in bacterial growth and metabolism were downregulated in B. theta from Tg rats
      with colitis though luminal bacterial concentrations were unaffected. Bacterial
      genes in the Gene Ontology molecular function "receptor activity", most of which
      encode nutrient binding proteins, were significantly upregulated in B. theta from
      Tg rats and include a SusC homolog that induces adaptive immune responses in Tg
      rats. CONCLUSIONS: B. theta induces colitis in HLA-B27 Tg rats, which is
      associated with regulation of bacterial genes in metabolic and nutrient binding
      pathways that may affect host immune responses. These studies of the host
      microbial dialogue may lead to the identification of novel microbial targets for
      IBD therapies.

PMID- 22880066
TI  - Melanopsin mediates retrograde visual signaling in the retina.
AB  - The canonical flow of visual signals proceeds from outer to inner retina
      (photoreceptors -> bipolar cells -> ganglion cells). However, melanopsin
      expressing ganglion cells are photosensitive and functional sustained light
      signaling to retinal dopaminergic interneurons persists in the absence of rods
      and cones. Here we show that the sustained-type light response of retinal
      dopamine neurons requires melanopsin and that the response is mediated by AMPA
      type glutamate receptors, defining a retrograde retinal visual signaling pathway
      that fully reverses the usual flow of light signals in retinal circuits.

PMID- 22880067
TI  - Climate change at northern latitudes: rising atmospheric humidity decreases
      transpiration, N-uptake and growth rate of hybrid aspen.
AB  - At northern latitudes a rise in atmospheric humidity and precipitation is
      predicted as a consequence of global climate change. We studied several growth
      and functional traits of hybrid aspen (Populus tremula L.*P. tremuloides Michx.)
      in response to elevated atmospheric humidity (on average 7% over the ambient
      level) in a free air experimental facility during three growing seasons (2008
      2010) in Estonia, which represents northern temperate climate (boreo-nemoral
      zone). Data were collected from three humidified (H) and three control (C) plots,
      and analysed using nested linear models. Elevated air humidity significantly
      reduced height, stem diameter and stem volume increments and transpiration of the
      trees whereas these effects remained highly significant also after considering
      the side effects from soil-related confounders within the 2.7 ha study area. Tree
      leaves were smaller, lighter and had lower leaf mass per area (LMA) in H plots.
      The magnitude and significance of the humidity treatment effect--inhibition of
      above-ground growth rate--was more pronounced in larger trees. The lower growth
      rate in the humidified plots can be partly explained by a decrease in
      transpiration-driven mass flow of NO(3) (-) in soil, resulting in a significant
      reduction in the measured uptake of N to foliage in the H plots. The results
      suggest that the potential growth improvement of fast-growing trees like aspens,
      due to increasing temperature and atmospheric CO(2) concentration, might be
      smaller than expected at high latitudes if a rise in atmospheric humidity
      simultaneously takes place.

PMID- 22880069
TI  - Assembly-history dynamics of a pitcher-plant protozoan community in experimental
      microcosms.
AB  - BACKGROUND: History drives community assembly through differences both in density
      (density effects) and in the sequence in which species arrive (sequence effects).
      Density effects arise from predictable population dynamics, which are free of
      history, but sequence effects are due to a density-free mechanism, arising solely
      from the order and timing of immigration events. Few studies have determined how
      components of immigration history (timing, number of individuals, frequency)
      alter local dynamics to determine community assembly, beyond addressing when
      immigration history produces historically contingent assembly. METHODS/FINDINGS:
      We varied density and sequence effects independently in a two-way factorial
      design to follow community assembly in a three-species aquatic protozoan
      community. A superior competitor, Colpoda steinii, mediated alternative community
      states; early arrival or high introduction density allowed this species to
      outcompete or suppress the other competitors (Poterioochromonas malhamensis and
      Eimeriidae gen. sp.). Multivariate analysis showed that density effects caused
      greater variation in community states, whereas sequence effects altered the mean
      community composition. CONCLUSIONS: A significant interaction between density and
      sequence effects suggests that we should refine our understanding of priority
      effects. These results highlight a practical need to understand not only the
      "ingredients" (species) in ecological communities but their "recipes" as well.

PMID- 22880068
TI  - Widespread state-dependent shifts in cerebellar activity in locomoting mice.
AB  - Excitatory drive enters the cerebellum via mossy fibers, which activate granule
      cells, and climbing fibers, which activate Purkinje cell dendrites. Until now,
      the coordinated regulation of these pathways has gone unmonitored in spatially
      resolved neuronal ensembles, especially in awake animals. We imaged cerebellar
      activity using functional two-photon microscopy and extracellular recording in
      awake mice locomoting on an air-cushioned spherical treadmill. We recorded from
      putative granule cells, molecular layer interneurons, and Purkinje cell dendrites
      in zone A of lobule IV/V, representing sensation and movement from trunk and
      limbs. Locomotion was associated with widespread increased activity in granule
      cells and interneurons, consistent with an increase in mossy fiber drive. At the
      same time, dendrites of different Purkinje cells showed increased co-activation,
      reflecting increased synchrony of climbing fiber activity. In resting animals,
      aversive stimuli triggered increased activity in granule cells and interneurons,
      as well as increased Purkinje cell co-activation that was strongest for
      neighboring dendrites and decreased smoothly as a function of mediolateral
      distance. In contrast with anesthetized recordings, no 1-10 Hz oscillations in
      climbing fiber activity were evident. Once locomotion began, responses to
      external stimuli in all three cell types were strongly suppressed. Thus climbing
      and mossy fiber representations can shift together within a fraction of a second,
      reflecting in turn either movement-associated activity or external stimuli.

PMID- 22880070
TI  - The role of the subthalamic nucleus in L-DOPA induced dyskinesia in 6
      hydroxydopamine lesioned rats.
AB  - L-DOPA is the most effective treatment for Parkinson's disease (PD), but
      prolonged use leads to disabling motor complications including dyskinesia. Strong
      evidence supports a role of the subthalamic nucleus (STN) in the pathophysiology
      of PD whereas its role in dyskinesia is a matter of controversy. Here, we
      investigated the involvement of STN in dyskinesia, using single-unit
      extracellular recording, behavioural and molecular approaches in hemi
      parkinsonian rats rendered dyskinetic by chronic L-DOPA administration. Our
      results show that chronic L-DOPA treatment does not modify the abnormal STN
      activity induced by the 6-hydroxydopamine lesion of the nigrostriatal pathway in
      this model. Likewise, we observed a loss of STN responsiveness to a single L-DOPA
      dose both in lesioned and sham animals that received daily L-DOPA treatment. We
      did not find any correlation between the abnormal involuntary movement (AIM)
      scores and the electrophysiological parameters of STN neurons recorded 24 h or 20
      120 min after the last L-DOPA injection, except for the axial subscores.
      Nonetheless, unilateral chemical ablation of the STN with ibotenic acid resulted
      in a reduction in global AIM scores and peak-severity of dyskinesia. In addition,
      STN lesion decreased the anti-dyskinetogenic effect of buspirone in a reciprocal
      manner. Striatal protein expression was altered in dyskinetic animals with
      increases in DeltaFosB, phosphoDARPP-32, dopamine receptor (DR) D3 and DRD2/DRD1
      ratio. The STN lesion attenuated the striatal molecular changes and normalized
      the DRD2/DRD1 ratio. Taken together, our results show that the STN plays a role,
      if modest, in the physiopathology of dyskinesias.

PMID- 22880071
TI  - Spontaneous cancer-stromal cell fusion as a mechanism of prostate cancer androgen
      independent progression.
AB  - We have previously shown that human prostate cancer cells are capable of
      acquiring malignant attributes through interaction with stromal cells in the
      tumor microenvironment, while the interacting stromal cells can also become
      affected with both phenotypic and genotypic alterations. This study used a co
      culture model to investigate the mechanism underlying the co-evolution of cancer
      and stromal cells. Red fluorescent androgen-dependent LNCaP prostate cancer cells
      were cultured with a matched pair of normal and cancer-associated prostate
      myofibroblast cells to simulate cancer-stromal interaction, and cellular changes
      in the co-culture were documented by tracking the red fluorescence. We found
      frequent spontaneous fusions between cancer and stromal cells throughout the co
      culture. In colony formation assays assessing the fate of the hybrid cells, most
      of the cancer-stromal fusion hybrids remained growth-arrested and eventually
      perished. However, some of the hybrids survived to form colonies from the co
      culture with cancer-associated stromal cells. These derivative clones showed
      genomic alterations together with androgen-independent phenotype. The results
      from this study reveal that prostate cancer cells are fusogenic, and cancer
      stromal interaction can lead to spontaneous fusion between the two cell types.
      While a cancer-stromal fusion strategy may allow the stromal compartment to
      annihilate invading cancer cells, certain cancer-stromal hybrids with increased
      survival capability may escape annihilation to form a derivative cancer cell
      population with an altered genotype and increased malignancy. Cancer-stromal
      fusion thus lays a foundation for an incessant co-evolution between cancer and
      the cancer-associated stromal cells in the tumor microenvironment.

PMID- 22880072
TI  - In vitro generation of monocyte-derived macrophages under serum-free conditions
      improves their tumor promoting functions.
AB  - The tumor promoting role of M2 macrophages has been described in in vivo models
      and the presence of macrophages in certain tumor types has been linked to a poor
      clinical outcome. In light of burgeoning activities to clinically develop new
      therapies targeting tumor-associated macrophages (TAMs), reliable in vitro models
      faithfully mimicking the tumor promoting functions of TAMs are required.
      Generation and activation of human monocyte-derived macrophages (MDM) in vitro,
      described as M1 or M2 macrophages attributed with tumoricidal or tumor-promoting
      functions, respectively, has been widely reported using mainly serum containing
      culture methods. In this study, we compared the properties of macrophages
      originating from monocytes cultured either in media containing serum together
      with M-CSF for M2 and GM-CSF for M1 macrophages or in serum-free media
      supplemented with M-CSF or GM-CSF and cytokines such as IL-4, IL-10 to induce
      activated M2 or LPS together with IFN-gamma to generate activated M1 phenotype.
      We observed differences in cell morphology as well as increased surface receptor
      expression levels in serum-containing culture whereas similar or higher cytokine
      production levels were detected under serum-free culture conditions. More
      importantly, MDM differentiated under serum-free conditions displayed enhanced
      tumoricidal activity for M1 and tumor promoting property for M2 macrophages in
      contrast to MDM differentiated in the presence of serum. Moreover, evaluation of
      MDM phagocytic activity in serum free condition resulted in greater phagocytic
      properties of M2 compared to M1. Our data therefore confirm the tumor promoting
      properties of M2 macrophages in vitro and encourage the targeting of TAMs for
      cancer therapy.

PMID- 22880073
TI  - Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo
      immune responses after cell transplantation.
AB  - Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi
      lineage potential which makes them attractive targets for regenerative medicine
      applications. However, to date, therapeutic success of MSC-therapy is limited and
      the genetic modification of MSCs using viral vectors is one option to improve
      their therapeutic potential. Ex-vivo genetic modification of MSCs using
      recombinant adenovirus (Ad) could be promising to reduce undesired immune
      responses as Ad will be removed before cell/tissue transplantation. In this
      regard, we investigated whether Ad-modification of MSCs alters their
      immunological properties in vitro and in vivo. We found that Ad-transduction of
      MSCs does not lead to up-regulation of major histocompatibility complex class I
      and II and co-stimulatory molecules CD80 and CD86. Moreover, Ad-transduction
      caused no significant changes in terms of pro-inflammatory cytokine expression,
      chemokine and chemokine receptor and Toll-like receptor expression. In addition,
      Ad-modification of MSCs had no affect on their ability to suppress T cell
      proliferation in vitro. In vivo injection of Ad-transduced MSCs did not change
      the frequency of various immune cell populations (antigen presenting cells, T
      helper and cytotoxic T cells, natural killer and natural killer T cells) neither
      in the blood nor in tissues. Our results indicate that Ad-modification has no
      major influence on the immunological properties of MSCs and therefore can be
      considered as a suitable gene vector for therapeutic applications of MSCs.

PMID- 22880074
TI  - Intranasal immunization with nontypeable Haemophilus influenzae outer membrane
      vesicles induces cross-protective immunity in mice.
AB  - Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act
      as a commensal and a pathogen of the respiratory tract. Especially nontypeable H.
      influenzae (NTHi) is a major threat to public health and is responsible for
      several infectious diseases in humans, such as pneumonia, sinusitis, and otitis
      media. Additionally, NTHi strains are highly associated with exacerbations in
      patients suffering from chronic obstructive pulmonary disease. Currently, there
      is no licensed vaccine against NTHi commercially available. Thus, this study
      investigated the utilization of outer membrane vesicles (OMVs) as a potential
      vaccine candidate against NTHi infections. We analyzed the immunogenic and
      protective properties of OMVs derived from various NTHi strains by means of
      nasopharyngeal immunization and colonization studies with BALB/c mice. The
      results presented herein demonstrate that an intranasal immunization with NTHi
      OMVs results in a robust and complex humoral and mucosal immune response.
      Immunoprecipitation revealed the most important immunogenic proteins, such as the
      heme utilization protein, protective surface antigen D15, heme binding protein A,
      and the outer membrane proteins P1, P2, P5 and P6. The induced immune response
      conferred not only protection against colonization with a homologous NTHi strain,
      which served as an OMV donor for the immunization mixtures, but also against a
      heterologous NTHi strain, whose OMVs were not part of the immunization mixtures.
      These findings indicate that OMVs derived from NTHi strains have a high potential
      to act as a vaccine against NTHi infections.

PMID- 22880076
TI  - Soil bacterial diversity screening using single 16S rRNA gene V regions coupled
      with multi-million read generating sequencing technologies.
AB  - The novel multi-million read generating sequencing technologies are very
      promising for resolving the immense soil 16S rRNA gene bacterial diversity. Yet
      they have a limited maximum sequence length screening ability, restricting
      studies in screening DNA stretches of single 16S rRNA gene hypervariable (V)
      regions. The aim of the present study was to assess the effects of properties of
      four consecutive V regions (V3-6) on commonly applied analytical methodologies in
      bacterial ecology studies. Using an in silico approach, the performance of each V
      region was compared with the complete 16S rRNA gene stretch. We assessed related
      properties of the soil derived bacterial sequence collection of the Ribosomal
      Database Project (RDP) database and concomitantly performed simulations based on
      published datasets. Results indicate that overall the most prominent V region for
      soil bacterial diversity studies was V3, even though it was outperformed in some
      of the tests. Despite its high performance during most tests, V4 was less
      conserved along flanking sites, thus reducing its ability for bacterial diversity
      coverage. V5 performed well in the non-redundant RDP database based analysis.
      However V5 did not resemble the full-length 16S rRNA gene sequence results as
      well as V3 and V4 did when the natural sequence frequency and occurrence
      approximation was considered in the virtual experiment. Although, the highly
      conserved flanking sequence regions of V6 provide the ability to amplify partial
      16S rRNA gene sequences from very diverse owners, it was demonstrated that V6 was
      the least informative compared to the rest examined V regions. Our results
      indicate that environment specific database exploration and theoretical
      assessment of the experimental approach are strongly suggested in 16S rRNA gene
      based bacterial diversity studies.

PMID- 22880075
TI  - The influence of therapeutic radiation on the patterns of bone marrow in ovary
      intact and ovariectomized mice.
AB  - BACKGROUND: The functional components of bone marrow (i.e., the hematopoietic and
      stromal populations) and the adjacent bone have traditionally been evaluated
      incompletely as distinct entities rather than the integrated system. We perturbed
      this system in vivo using a medically relevant radiation model in the presence or
      absence of ovarian function to understand integrated tissue interaction.
      METHODOLOGY/PRINCIPAL FINDINGS: Ovary-intact and ovariectomized mice underwent
      either no radiation or single fractional 16 Gy radiation to the caudal skeleton
      (I +/- R, OVX +/- R). Marrow fat, hematopoietic cellularity, and cancellous bone
      volume fraction (BV/TV %) were assessed. Ovariectomy alone did not significantly
      reduce marrow cellularity in non-irradiated mice (OVX-R vs. I-R, p = 0.8445)
      after 30 days; however it impaired the hematopoietic recovery of marrow following
      radiation exposure (OVX+R vs. I+R, p = 0.0092). The combination of radiation and
      OVX dramatically increases marrow fat compared to either factor alone (p =
      0.0062). The synergistic effect was also apparent in the reduction of
      hematopoietic marrow cellularity (p = 0.0661); however it was absent in BV/TV%
      changes (p = 0.2520). The expected inverse relationship between marrow adiposity
      vs. hematopoietic cellularity and bone volume was observed. Interestingly
      compared with OVX mice, intact mice demonstrated double the reduction in
      hematopoietic cellularity and a tenfold greater degree of bone loss for a given
      unit of expansion in marrow fat. CONCLUSIONS/SIGNIFICANCE: Ovariectomy prior to
      delivery of a clinically-relevant focal radiation exposure in mice, exacerbated
      post-radiation adipose accumulation in the marrow space but blunted bone loss and
      hematopoietic suppression. In the normally coupled homeostatic relationship
      between the bone and marrow domains, OVX appears to alter feedback mechanisms.
      Confirmation of this non-linear phenomenon (presumably due to differential
      radiosensitivity) and demonstration of the mechanism of action is needed to
      provide strategies to diminish the effect of radiation on exposed tissues.

PMID- 22880077
TI  - Individuals' decision to co-donate or donate alone: an archival study of married
      whole body donors in Hawaii.
AB  - BACKGROUND: Human cadavers are crucial to numerous aspects of health care,
      including initial and continuing training of medical doctors and advancement of
      medical research. Concerns have periodically been raised about the limited number
      of whole body donations. Little is known, however, about a unique form of
      donation, namely co-donations or instances when married individuals decide to
      register at the same time as their spouse as whole body donors. Our study aims to
      determine the extent of whole body co-donation and individual factors that might
      influence co-donation. METHODS AND FINDINGS: We reviewed all records of
      registrants to the University of Hawaii Medical School's whole body donation
      program from 1967 through 2006 to identify married registrants. We then examined
      the 806 married individuals' characteristics to understand their decision to
      register alone or with their spouse. We found that married individuals who
      registered at the same time as their spouse accounted for 38.2 percent of married
      registrants. Sex differences provided an initial lens to understand co-donation.
      Wives were more likely to co-donate than to register alone (p = 0.002). Moreover,
      registrants' main occupational background had a significant effect on co
      donations (p = 0.001). Married registrants (regardless of sex) in female-gendered
      occupations were more likely to co-donate than to donate alone (p = 0.014).
      Female-gendered occupations were defined as ones in which women represented more
      than 55 percent of the workforce (e.g., preschool teachers). Thus, variations in
      donors' occupational backgrounds explained co-donation above and beyond sex
      differences. CONCLUSIONS: Efforts to secure whole body donations have
      historically focused on individual donations regardless of donors' marital
      status. More attention needs to be paid, however, to co-donations since they
      represent a non-trivial number of total donations. Also, targeted outreach
      efforts to male and female members of female-gendered occupations might prove a
      successful way to increase donations through co-donations.

PMID- 22880078
TI  - Lack of neuropsychological deficits in generalized social phobia.
AB  - There are relatively few existing studies examining neuropsychological
      functioning in social phobia (SP), which collectively yield mixed results.
      Interpretation of results is further complicated by a number of methodological
      inconsistencies across studies, including the examination of neuropsychological
      domains in relative isolation from one another. The present study utilized a
      broader collection of neuropsychological tests to assess nine domains of
      functioning in 25 individuals diagnosed with generalized SP and 25 nonpsychiatric
      controls (NC). A mixed ANOVA revealed neither a significant group by domain
      interaction, nor a significant main effect of group. Furthermore, no significant
      group differences emerged between the SP and NC groups within each specific
      neuropsychological domain. These findings suggest that underlying
      neuropsychological deficits are not likely to account for the information
      processing biases observed in the empirical literature, and appear to be
      consistent with current theoretical models which argue for the specificity of
      these biases to social information.

PMID- 22880079
TI  - Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but
      not its precursor proBDNF, in patients with major depressive disorder.
AB  - BACKGROUND: Meta-analyses have identified serum levels of brain-derived
      neurotrophic factor (BDNF) as a potential biomarker for major depressive disorder
      (MDD). However, at the time, commercially available human ELISA kits are unable
      to distinguish between proBDNF (precursor of BDNF) and mature BDNF because of
      limited BDNF antibody specificity. In this study, we examined whether serum
      levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9), which
      converts proBDNF to mature BDNF, are altered in patients with MDD.
      METHODOLOGY/PRINCIPAL FINDINGS: Sixty-nine patients with MDD and 78 age- and
      gender-matched healthy subjects were enrolled. Patients were evaluated using 17
      items on the Structured Interview Guide for the Hamilton Depression Rating Scale.
      Cognitive impairment was evaluated using the CogState battery. Serum levels of
      proBDNF, mature BDNF, and MMP-9 were measured using ELISA kits. Serum levels of
      mature BDNF in patients with MDD were significantly lower than those of normal
      controls. In contrast, there was no difference in the serum levels of proBDNF and
      MMP-9 between patients and normal controls. While neither proBDNF nor mature BDNF
      serum levels was associated with clinical variables, there were significant
      correlations between MMP-9 serum levels and the severity of depression, quality
      of life scores, and social function scores in patients. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest that mature BDNF may serve as a biomarker for MDD, and
      that MMP-9 may play a role in the pathophysiology of MDD. Further studies using
      larger sample sizes will be needed to investigate these results.

PMID- 22880080
TI  - Impact of sex steroid ablation on viral, tumour and vaccine responses in aged
      mice.
AB  - Recent evidence suggests that the decline in resistance to viral infections with
      age occurs predominantly as a result of a gradual loss of naive antigen-specific
      T cells. As such, restoration of the naive T cell repertoire to levels seen in
      young healthy adults may improve defence against infection in the aged. We have
      previously shown that sex steroid ablation (SSA) rejuvenates the ageing thymus
      and increases thymic export of naive T cells, but it remains unclear whether T
      cell responses are improved. Using mouse models of clinically relevant diseases,
      we now demonstrate that SSA increases the number of naive T cells able to respond
      to antigen, thereby enhancing effector responses in aged mice. Specifically, aged
      mice exhibit a delay in clearing influenza A virus, which correlates with
      diminished specific cytotoxic activity. This is due to a decreased magnitude of
      response and not an intrinsic defect in effector T cell function. Upon SSA, aged
      mice exhibit increased T cell responsiveness that restores efficient viral
      clearance. We further demonstrate that SSA decreases the incidence of an
      inducible tumour in aged mice and can potentially increase their responsiveness
      to a low-dose human papillomavirus vaccine in clearing pre-formed tumours. As
      thymectomy abrogates the increase in T cell numbers and responsiveness following
      SSA, we propose that the T cell effects of SSA are dependent on thymic
      reactivation and subsequent replenishment of the peripheral T cell pool with
      newly emigrated naive T cells. These findings have important implications for
      strategies to improve protection from infection and responsiveness to vaccination
      in the aged.

PMID- 22880081
TI  - Mis-assembled "segmental duplications" in two versions of the Bos taurus genome.
AB  - We analyzed the whole genome sequence coverage in two versions of the Bos taurus
      genome and identified all regions longer than five kilobases (Kbp) that are
      duplicated within chromosomes with >99% sequence fidelity in both copies. We call
      these regions High Fidelity Duplications (HFDs). The two assemblies were Btau
      4.2, produced by the Human Genome Sequencing Center at Baylor College of
      Medicine, and UMD Bos taurus 3.1 (UMD 3.1), produced by our group at the
      University of Maryland. We found that Btau 4.2 has a far greater number of HFDs,
      3111 versus only 69 in UMD 3.1. Read coverage analysis shows that 39 million base
      pairs (Mbp) of sequence in HFDs in Btau 4.2 appear to be a result of a mis
      assembly and therefore cannot be qualified as segmental duplications. UMD 3.1 has
      only 0.41 Mbp of sequence in HFDs that are due to a mis-assembly.

PMID- 22880083
TI  - The evolutionary history of the Arabidopsis arenosa complex: diverse tetraploids
      mask the Western Carpathian center of species and genetic diversity.
AB  - The Arabidopsis arenosa complex is closely related to the model plant Arabidopsis
      thaliana. Species and subspecies in the complex are mainly biennial,
      predominantly outcrossing, herbaceous, and with a distribution range covering
      most parts of latitudes and the eastern reaches of Europe. In this study we
      present the first comprehensive evolutionary history of the A. arenosa species
      complex, covering its natural range, by using chromosome counts, nuclear AFLP
      data, and a maternally inherited marker from the chloroplast genome [trnL intron
      (trnL) and trnL/F intergenic spacer (trnL/F-IGS) of tRNA(Leu) and tRNA(Phe),
      respectively]. We unravel the broad-scale cytogeographic and phylogeographic
      patterns of diploids and tetraploids. Diploid cytotypes were exclusively found on
      the Balkan Peninsula and in the Carpathians while tetraploid cytotypes were found
      throughout the remaining distribution range of the A. arenosa complex. Three
      centers of genetic diversity were identified: the Balkan Peninsula, the
      Carpathians, and the unglaciated Eastern and Southeastern Alps. All three could
      have served as long-term refugia during Pleistocene climate oscillations. We
      hypothesize that the Western Carpathians were and still are the cradle of
      speciation within the A. arenosa complex due to the high species number and
      genetic diversity and the concurrence of both cytotypes there.

PMID- 22880082
TI  - The guanine-quadruplex structure in the human c-myc gene's promoter is converted
      into B-DNA form by the human poly(ADP-ribose)polymerase-1.
AB  - The important regulatory role of the guanine-quadruplex (GQ) structure, present
      in the nuclease hypersensitive element (NHE) III(1) region of the human c-myc (h
      c-myc) gene's promoter, in the regulation of the transcription of that gene has
      been documented. Here we present evidences, that the human nuclear poly(ADP
      ribose)polymerase-1 (h PARP-1) protein participates in the regulation of the h c
      myc gene expression through its interaction with this GQ structure, characterized
      by binding assays, fluorescence energy transfer (FRET) experiments and by
      affinity pull-down experiments in vitro, and by chromatin immunoprecipitation
      (ChIP)-qPCR analysis and h c-myc-promoter-luciferase reporter determinations in
      vivo. We surmise that h PARP-1 binds to the GQ structure and participates in the
      conversion of that structure into the transcriptionally more active B-DNA form.
      The first Zn-finger structure present in h PARP-1 participates in this
      interaction. PARP-1 might be a new member of the group of proteins participating
      in the regulation of transcription through their interactions with GQ structures
      present in the promoters of different genes.

PMID- 22880084
TI  - The "CPC clip motif": a conserved structural signature for heparin-binding
      proteins.
AB  - Glycosaminoglycans (GAGs) are essential molecules that regulate diverse
      biological processes including cell adhesion, differentiation, signaling and
      growth, by interaction with a wide variety of proteins. However, despite the
      efforts committed to understand the molecular nature of the interactions in
      protein-GAG complexes, the answer to this question remains elusive.In the present
      study the interphases of 20 heparin-binding proteins have been analyzed searching
      for a conserved structural pattern. We have found that a structural motif
      encompassing one polar and two cationic residues (which has been named the CPC
      clip motif) is conserved among all the proteins deposited in the PDB. The
      distances between the alpha carbons and the side chain center of gravity of the
      residues composing this motif are also conserved. Furthermore, this pattern can
      be found in other proteins suggested to bind heparin for which no structural
      information is available. Hence we propose that the CPC clip motif, working like
      a staple, is a primary contributor to the attachment of heparin and other
      sulfated GAGs to heparin-binding proteins.

PMID- 22880085
TI  - ADAM10 regulates transcription factor expression required for plasma cell
      function.
AB  - A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular
      processes by shedding extracellular domains of transmembrane proteins. We have
      previously demonstrated that deletion of B cell expressed ADAM10 results in
      changes in lymphoid tissue architecture and impaired germinal center (GC)
      formation. In this study, mice were generated in which ADAM10 is deleted in B
      cells following class switch recombination (ADAM10(Delta/Delta)IgG1-cre(+/-)
      mice). Despite normal GC formation, antibody responses were impaired in
      ADAM10(Delta/Delta)IgG1-cre(+/-) mice, implicating ADAM10 in post-GC and
      extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC)
      numbers were normal in ADAM10(Delta/Delta)IgG1-cre(+/-) mice when compared to
      controls. However, PCs isolated from ADAM10(Delta/Delta)IgG1-cre(+/-) mice
      exhibited decreased expression of transcription factors important for PC
      function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that
      inhibits the PC transcriptional program and thus must be downregulated for PC
      differentiation to occur. Bcl6 expression was increased in PCs isolated from
      ADAM10(Delta/Delta)IgG1-cre(+/-) mice at both the mRNA and protein level. These
      results demonstrate that ADAM10 is required for proper transcription factor
      expression in PCs and thus, for normal PC function.

PMID- 22880086
TI  - A safety review and meta-analyses of bevacizumab and ranibizumab: off-label
      versus goldstandard.
AB  - BACKGROUND: We set out a systemic review to evaluate whether off-label
      bevacizumab is as safe as licensed ranibizumab, and whether bevacizumab can be
      justifiably offered to patients as a treatment for age-related macular
      degeneration with robust evidence of no differential risk. METHODS AND FINDINGS:
      Medline, Embase and the Cochrane Library were searched with no limitations of
      language and year of publication. We included RCTs with a minimum follow-up of
      one year which investigated bevacizumab or ranibizumab in direct comparison or
      against any other control group (indirect comparison). Direct comparison (3
      trials, 1333 patients): The one year data show a significantly higher rate of
      ocular adverse effects (AE) with bevacizumab compared to ranibizumab (RR = 2.8;
      95% CI 1.2-6.5). The proportion of patients with serious infections and
      gastrointestinal disorders was also higher with bevacizumab than with ranibizumab
      (RR = 1.3; 95% CI 1.0-1.7). Arterial thromboembolic events were equally
      distributed among the groups. Indirect comparison: Ranibizumab versus any control
      (5 trials, 4054 patients): The two year results of three landmark trials showed
      that while absolute rates of serious ocular AE were low (<= 2.1%), relative harm
      was significantly raised (RR = 3.1; 95% CI 1.1-8.9). A significant increase in
      nonocular haemorrhage was also observed with ranibizumab (RR = 1.7; 95% CI 1.1
      2.7). Bevacizumab versus any control (3 trials, 244 patients): We were unable to
      judge the safety profile of bevacizumab due to the poor quality of AE monitoring
      and reporting in the trials. CONCLUSIONS: Evidence from head-to-head trials
      raises concern about an increased risk of ocular and multiple systemic AE with
      bevacizumab. Therefore, clinicians and patients should continue to carefully
      weight up the benefits and harms when choosing between the two treatment options.
      We also emphasize the need for studies that are powered not just for efficacy,
      but for defined safety outcomes based on the signals detected in this systematic
      review.

PMID- 22880088
TI  - A lack of sexual dimorphism in width-to-height ratio in white European faces
      using 2D photographs, 3D scans, and anthropometry.
AB  - Facial width-to-height ratio has received a great deal of attention in recent
      research. Evidence from human skulls suggests that males have a larger relative
      facial width than females, and that this sexual dimorphism is an honest signal of
      masculinity, aggression, and related traits. However, evidence that this measure
      is sexually dimorphic in faces, rather than skulls, is surprisingly weak. We
      therefore investigated facial width-to-height ratio in three White European
      samples using three different methods of measurement: 2D photographs, 3D scans,
      and anthropometry. By measuring the same individuals with multiple methods, we
      demonstrated high agreement across all measures. However, we found no evidence of
      sexual dimorphism in the face. In our third study, we also found a link between
      facial width-to-height ratio and body mass index for both males and females,
      although this relationship did not account for the lack of dimorphism in our
      sample. While we showed sufficient power to detect differences between male and
      female width-to-height ratio, our results failed to support the general
      hypothesis of sexual dimorphism in the face.

PMID- 22880087
TI  - Aberrant promoter methylation and expression of UTF1 during cervical
      carcinogenesis.
AB  - Promoter methylation profiles are proposed as potential prognosis and/or
      diagnosis biomarkers in cervical cancer. Up to now, little is known about the
      promoter methylation profile and expression pattern of stem cell (SC) markers
      during tumor development. In this study, we were interested to identify SC genes
      methylation profiles during cervical carcinogenesis. A genome-wide promoter
      methylation screening revealed a strong hypermethylation of Undifferentiated cell
      Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with
      normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid
      based cytological samples, we showed that UTF1 promoter methylation increases
      with lesion severity, the highest level of methylation being found in carcinoma.
      This hypermethylation was associated with increased UTF1 mRNA and protein
      expression. By using quantitative RT-PCR and Western Blot, we showed that both
      UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the
      absence of its two main described regulators Oct4A and Sox2. Moreover, by
      immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines.
      Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA
      methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1
      gene methylation and expression in two cervical cancer cell lines of the four
      tested. These findings strongly suggest that UTF1 promoter methylation profile
      might be a useful biomarker for cervical cancer diagnosis and raise the questions
      of its role during epithelial carcinogenesis and of the mechanisms regulating its
      expression.

PMID- 22880089
TI  - Ecosystem services transcend boundaries: estuaries provide resource subsidies and
      influence functional diversity in coastal benthic communities.
AB  - BACKGROUND: Estuaries are highly productive ecosystems that can export organic
      matter to coastal seas (the 'outwelling hypothesis'). However the role of this
      food resource subsidy on coastal ecosystem functioning has not been examined.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated the influence of estuarine
      primary production as a resource subsidy and the influence of estuaries on
      biodiversity and ecosystem functioning in coastal mollusk-dominated sediment
      communities. Stable isotope values (delta(13)C, delta(15)N) demonstrated that
      estuarine primary production was exported to the adjacent coast and contributed
      to secondary production up to 4 km from the estuary mouth. Further, isotope
      signatures of suspension feeding bivalves on the adjacent coast (Dosinia
      subrosea) closely mirrored the isotope values of the dominant bivalves inside the
      estuaries (Austrovenus stutchburyi), indicating utilization of similar organic
      matter sources. However, the food subsidies varied between estuaries; with
      estuarine suspended particulate organic matter (SPOM) dominant at Tairua estuary,
      while seagrass and fringing vegetation detritus was proportionately more
      important at Whangapoua estuary, with lesser contributions of estuarine SPOM.
      Distance from the estuary mouth and the size and density of large bivalves
      (Dosinia spp.) had a significant influence on the composition of biological
      traits in the coastal macrobenthic communities, signaling the potential influence
      of these spatial subsidies on ecosystem functioning. CONCLUSIONS/SIGNIFICANCE:
      Our study demonstrated that the locations where ecosystem services like
      productivity are generated are not necessarily where the services are utilized.
      Further, we identified indirect positive effects of the nutrient subsidies on
      biodiversity (the estuarine subsidies influenced the bivalves, which in turn
      affected the diversity and functional trait composition of the coastal sediment
      macrofaunal communities). These findings highlight the importance of integrative
      ecosystem-based management that maintains the connectivity of estuarine and
      coastal ecosystems.

PMID- 22880090
TI  - Variation of Mycobacterium tuberculosis antigen-specific IFN-gamma and IL-17
      responses in healthy tuberculin skin test (TST)-positive human subjects.
AB  - OBJECTIVE: To determine the variation of IFN-gamma and IL-17 responses to M.
      tuberculosis antigens in healthy TST+ humans. METHODS: We isolated peripheral
      blood mononuclear cells from 21 TST+ healthy adults, stimulated them with
      phytohemagglutinin (PHA), PPD, Ag85B, ESAT-6, and live M. bovis BCG, and assayed
      IFN-gamma and IL-17 secretion by ELISA in supernatants after 24 or 72 hours of
      incubation respectively. RESULTS: As in other studies, we found a wide range of
      IFN-gamma responses to M. tuberculosis antigens; the variation significantly
      exceeded that observed in the same donors to the polyclonal T cell stimulus,
      phytohemagglutinin (PHA). In addition, we assayed IL-17 secretion in response to
      the same stimuli, and found less subject-to-subject variation. Analysis of the
      ratio of IFN-gamma to IL-17 secretion on a subject-to-subject basis also revealed
      a wide range, with the majority of results distributed in a narrow range, and a
      minority with extreme results all of which were greater than that in the majority
      of subjects. The data suggest that study of exceptional responses to M.
      tuberculosis antigens may reveal immunologic correlates with specific outcomes of
      M. tuberculosis infection. CONCLUSION: Variation of IFNgamma and IFN-gamma/IL-17
      responses to mycobacterial antigens exceeds that of responses to the polyclonal
      stimulus, PHA, in TST positive healthy humans. This indicates a quantitative
      spectrum of human immune responses to infection with M. tuberculosis. Since the
      outcome of human infection with M. tuberculosis varies greatly, systematic study
      of multiple immune responses to multiple antigens is likely to reveal
      correlations between selected immune responses and the outcomes of infection.

PMID- 22880091
TI  - Methane carbon supports aquatic food webs to the fish level.
AB  - Large amounts of the greenhouse gas methane (CH(4)) are produced by anaerobic
      mineralization of organic matter in lakes. In spite of extensive freshwater CH(4)
      emissions, most of the CH(4) is typically oxidized by methane oxidizing bacteria
      (MOB) before it can reach the lake surface and be emitted to the atmosphere. In
      turn, it has been shown that the CH(4)-derived biomass of MOB can provide the
      energy and carbon for zooplankton and macroinvertebrates. In this study, we
      demonstrate the presence of specific fatty acids synthesized by MOB in fish
      tissues having low carbon stable isotope ratios. Fish species, zooplankton,
      macroinvertebrates and the water hyacinth Eichhornia crassipes were collected
      from a shallow lake in Brazil and analyzed for fatty acids (FA) and carbon stable
      isotope ratios (delta(13)C). The fatty acids 16:1omega8c, 16:1omega8t,
      16:1omega6c, 16:1omega5t, 18:1omega8c and 18:1omega8t were used as signature for
      MOB. The delta(13)C ratios varied from -27.70/00 to -42.00/00 and the
      contribution of MOB FA ranged from 0.05% to 0.84% of total FA. Organisms with
      higher total content of MOB FAs presented lower delta(13)C values (i.e. they were
      more depleted in (13)C), while organisms with lower content of MOB signature FAs
      showed higher delta(13)C values. An UPGMA cluster analysis was carried out to
      distinguish grouping of organisms in relation to their MOB FA contents. This
      combination of stable isotope and fatty acid tracers provides new evidence that
      assimilation of methane-derived carbon can be an important carbon source for the
      whole aquatic food web, up to the fish level.

PMID- 22880092
TI  - A molecular epidemiology survey of respiratory adenoviruses circulating in
      children residing in Southern Palestine.
AB  - A molecular epidemiology survey was performed in order to establish and document
      the respiratory adenovirus pathogen profiles among children in Southern
      Palestine. Three hundred and thirty-eight hospitalized pediatric cases with
      adenovirus-associated respiratory tract infections were analyzed. Forty four
      cases out of the 338 were evaluated in more detail for the adenoviruses types
      present. All of the children resided in Southern Palestine, that is, in city,
      village and refugee camp environments within the districts of Hebron and
      Bethlehem. Human adenoviruses circulated throughout 2005-2010, with major
      outbreaks occurring in the spring months. A larger percent of the children
      diagnosed with adenoviral infections were male infants. DNA sequence analysis of
      the hexon genes from 44 samples revealed that several distinct adenovirus types
      circulated in the region; these were HAdV-C1, HAdV-C2, HAdV-B3 and HAdV-C5.
      However, not all of these types were detected within each year. This is the first
      study ever conducted in Palestine of the genetic epidemiology of respiratory
      adenovirus infections.

PMID- 22880093
TI  - Association between FGFR1OP2/wit3.0 polymorphisms and residual ridge resorption
      of mandible in Korean population.
AB  - BACKGROUND: A previous study on the genetic association between single nucleotide
      polymorphisms in FGFR1OP2/wit3.0 and the long term atrophy of edentulous mandible
      hypothesized that the excessive jawbone atrophy after dental extraction may be
      associated with abnormal oral mucosa contraction induced by the FGFR1OP2/wit 3.0
      gene. It was reported that the minor allele of rs840869 or rs859024 in
      FGFR1OP2/wit3.0 was associated with the excessive atrophy of edentulous mandible.
      The present study represents an attempt to replicate the results of this previous
      study and to examine the genetic association between polymorphisms in FGFR1OP2
      and residual ridge resorption of mandible in a Korean population.
      METHODOLOGY/PRINCIPAL FINDINGS: 134 subjects (70.46 +/- 9.02 years) with
      partially or completely edentulous mandible were recruited. The mandibular bone
      height was measured following the protocol of the American College of
      Prosthodontists (ACP). From 24 subjects, seven variants in FGFR1OP2 were
      discovered and four of them were novel. Selected SNPs that are not in high LD at
      r2 threshold of 0.8 were genotyped for the remaining population. There was no
      frequency of the minor allele of SNP rs859024 in Korean population. SNP rs840869
      was not associated with residual ridge resorption (p = 0.479). The bone height of
      the subject with the ss518063493 minor allele (8.52 mm) was shorter than that of
      those subjects with major alleles (18.96 +/- 5.33 mm, p = 0.053).
      CONCLUSIONS/SIGNIFICANCE: The patient with minor allele of ss518063493 may be
      associated with excessive atrophy of edentulous mandible whereas the patients
      with that of rs840869 are not associated in Korean population. The result from
      this study may assist in developing a novel genetic diagnostic test and be useful
      in identifying Koreans susceptible to developing excessive jawbone atrophy after
      dental extraction.

PMID- 22880094
TI  - p100 Deficiency is insufficient for full activation of the alternative NF-kappaB
      pathway: TNF cooperates with p52-RelB in target gene transcription.
AB  - BACKGROUND: Constitutive activation of the alternative NF-kappaB pathway leads to
      marginal zone B cell expansion and disorganized spleen microarchitecture.
      Furthermore, uncontrolled alternative NF-kappaB signaling may result in the
      development and progression of cancer. Here, we focused on the question how does
      the constitutive alternative NF-kappaB signaling exert its effects in these
      malignant processes. METHODOLOGY/PRINCIPAL FINDINGS: To explore the consequences
      of unrestricted alternative NF-kappaB activation on genome-wide transcription, we
      compared gene expression profiles of wild-type and NF-kappaB2/p100-deficient
      (p100(-/-)) primary mouse embryonic fibroblasts (MEFs) and spleens. Microarray
      experiments revealed only 73 differentially regulated genes in p100(-/-) vs. wild
      type MEFs. Chromatin immunoprecipitation (ChIP) assays showed in p100(-/-) MEFs
      direct binding of p52 and RelB to the promoter of the Enpp2 gene encoding
      ENPP2/Autotaxin, a protein with an important role in lymphocyte homing and cell
      migration. Gene ontology analysis revealed upregulation of genes with anti
      apoptotic/proliferative activity (Enpp2/Atx, Serpina3g, Traf1, Rrad),
      chemotactic/locomotory activity (Enpp2/Atx, Ccl8), and lymphocyte homing activity
      (Enpp2/Atx, Cd34). Most importantly, biochemical and gene expression analyses of
      MEFs and spleen, respectively, indicated a marked crosstalk between classical and
      alternative NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: Our results show that
      p100 deficiency alone was insufficient for full induction of genes regulated by
      the alternative NF-kappaB pathway. Moreover, alternative NF-kappaB signaling
      strongly synergized both in vitro and in vivo with classical NF-kappaB
      activation, thereby extending the number of genes under the control of the p100
      inhibitor of the alternative NF-kappaB signaling pathway.

PMID- 22880095
TI  - The effect of chronic deafferentation on mental imagery: a case study.
AB  - Visual- and motor imagery rely primarily on perceptual and motor processes,
      respectively. In healthy controls, the type of imagery used to solve a task
      depends on personal preference, task instruction, and task properties. But how
      does the chronic loss of proprioceptive and tactile sensory inputs from the body
      periphery influence mental imagery? In a unique case study, we investigated the
      imagery capabilities of the chronically deafferented patient IW when he was
      performing a mental rotation task. We found that IW's motor imagery processes
      were impaired and that visual imagery processes were enhanced compared to
      controls. These results suggest that kinaesthetic afferent signals from the body
      periphery play a crucial role in enabling and maintaining central sensorimotor
      representations and hence the ability to incorporate kinaesthetic information
      into the imagery processes.

PMID- 22880096
TI  - Cerebrospinal fluid glucose and lactate: age-specific reference values and
      implications for clinical practice.
AB  - Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up
      of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma
      glucose ratio and CSF lactate based on studies with large numbers of CSF samples
      are not available. Our aim was to define age-specific reference values. In 1993
      The Nijmegen Observational CSF Study was started. Results of all CSF samples that
      were analyzed between 1993 and 2008 at our laboratory were systematically
      collected and stored in our computerized database. After exclusion of CSF samples
      with an unknown or elevated erythrocyte count, an elevated leucocyte count,
      elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF
      samples were further studied for CSF glucose (n = 8,871), CSF/plasma glucose
      ratio (n = 4,516) and CSF lactate values (n = 7,614). CSF glucose, CSF/plasma
      glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific
      reference ranges were defined as 5-95(th) percentile ranges. CSF glucose 5(th)
      percentile values ranged from 1.8 to 2.9 mmol/L and 95(th) percentile values from
      3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5(th) percentile values ranged from
      0.41 to 0.53 and 95(th) percentile values from 0.82 to 1.19. CSF lactate 5(th)
      percentile values ranged from 0.88 to 1.41 mmol/L and 95(th) percentile values
      from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest
      in neonates and narrowest in toddlers, with lower and upper limits increasing
      with age. These reference values allow a reliable interpretation of CSF results
      in everyday clinical practice. Furthermore, hypoglycemia was associated with an
      increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the
      CSF/plasma glucose ratio.

PMID- 22880097
TI  - Similar health benefits of endurance and high-intensity interval training in
      obese children.
AB  - PURPOSE: To compare two modalities of exercise training (i.e., Endurance Training
      [ET] and High-Intensity Interval Training [HIT]) on health-related parameters in
      obese children aged between 8 and 12 years. METHODS: Thirty obese children were
      randomly allocated into either the ET or HIT group. The ET group performed a 30
      to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT
      group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity
      interspersed by a 3-min active recovery period at 50% of the exercise velocity.
      HIT sessions last ~70% less than ET sessions. At baseline and after 12 weeks of
      intervention, aerobic fitness, body composition and metabolic parameters were
      assessed. RESULTS: BOTH THE ABSOLUTE (ET: 26.0%; HIT: 19.0%) and the relative
      VO(2) peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups
      after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT:
      16.4%) and the peak velocity during the maximal graded cardiorespiratory test
      (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions.
      Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were
      significantly lower for both groups at POST when compared to PRE. Body mass was
      significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A
      significant reduction in BMI was observed for both groups after the intervention
      (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar
      pattern of the most responsive variables among groups. CONCLUSION: HIT and ET
      were equally effective in improving important health related parameters in obese
      youth.

PMID- 22880098
TI  - Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical
      circuits.
AB  - BACKGROUND: Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels
      generate the pacemaking current, I(h), which regulates neuronal excitability,
      burst firing activity, rhythmogenesis, and synaptic integration. The
      physiological consequence of HCN activation depends on regulation of channel
      gating by endogenous modulators and stabilization of the channel complex formed
      by principal and ancillary subunits. KCNE2 is a voltage-gated potassium channel
      ancillary subunit that also regulates heterologously expressed HCN channels;
      whether KCNE2 regulates neuronal HCN channel function is unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of Kcne2 gene
      deletion on I(h) properties and excitability in ventrobasal (VB) and cortical
      layer 6 pyramidal neurons using brain slices prepared from Kcne2(+/+) and Kcne2(
      /-) mice. Kcne2 deletion shifted the voltage-dependence of I(h) activation to
      more hyperpolarized potentials, slowed gating kinetics, and decreased I(h)
      density. Kcne2 deletion was associated with a reduction in whole-brain expression
      of both HCN1 and HCN2 (but not HCN4), although co-immunoprecipitation from whole
      brain lysates failed to detect interaction of KCNE2 with HCN1 or 2. Kcne2
      deletion also increased input resistance and temporal summation of subthreshold
      voltage responses; this increased intrinsic excitability enhanced burst firing in
      response to 4-aminopyridine. Burst duration increased in corticothalamic, but not
      thalamocortical, neurons, suggesting enhanced cortical excitatory input to the
      thalamus; such augmented excitability did not result from changes in glutamate
      release machinery since miniature EPSC frequency was unaltered in Kcne2(-/-)
      neurons. CONCLUSIONS/SIGNIFICANCE: Loss of KCNE2 leads to downregulation of HCN
      channel function associated with increased excitability in neurons in the cortico
      thalamo-cortical loop. Such findings further our understanding of the normal
      physiology of brain circuitry critically involved in cognition and have
      implications for our understanding of various disorders of consciousness.

PMID- 22880099
TI  - Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on
      chromosome 6p21 and risk of nasopharyngeal carcinoma.
AB  - BACKGROUND: The association between human leukocyte antigen (HLA) genes (located
      in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC
      has been known for some time. Recently, two genome-wide association studies
      (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for
      NPC association was mapped to the MHC region. It is still unclear, however,
      whether these findings reflect direct associations with Human Leukocyte Antigen
      (HLA) genes and/or to other genes in this gene-rich region. METHODS: To better
      understand genetic associations for NPC within the MHC region of chromosome 6, we
      conducted an evaluation that pooled two previously conducted NPC case-control
      studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was
      performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS
      and for the HLA-A gene (exons 2 and 3). FINDINGS: After confirming homogeneity
      between the two studies, pooled odds ratios (OR) and 95% confidence intervals
      (CI) were estimated by logistic regression. We found that HLA-A (p-trend =
      0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent
      risk factors for NPC after adjustment for age, gender, study and each other. NPC
      risk was highest among individuals who were homozygous for the HLA-A*0207 risk
      allele and carriers of the rs29232 risk allele (A). CONCLUSION: Our study
      suggests that most of the SNPs significantly associated with NPC from GWAS
      reflect previously identified HLA-A associations. An independent effect of
      rs29232 (GABBR1), however, remained, suggesting that additional genes within this
      region might be associated with NPC risk.

PMID- 22880100
TI  - A preliminary investigation into the impact of a pesticide combination on human
      neuronal and glial cell lines in vitro.
AB  - Many pesticides are used increasingly in combinations during crop protection and
      their stability ensures the presence of such combinations in foodstuffs. The
      effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were
      investigated together and separately on U251 and SH-SY5Y cells, which can be
      representative of human CNS glial and neuronal cells respectively. Over 48h, all
      three agents showed significant reductions in cellular ATP, at concentrations
      that were more than tenfold lower than those which significantly impaired
      cellular viability. The effects on energy metabolism were reflected in their
      marked toxic effects on mitochondrial membrane potential. In addition, evidence
      of oxidative stress was seen in terms of a fall in cellular thiols coupled with
      increases in the expression of enzymes associated with reactive species
      formation, such as GSH peroxidase and superoxide dismutase. The glial cell line
      showed significant responsiveness to the toxin challenge in terms of changes in
      antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater
      vulnerability to toxicity, which was reflected in significant increases in
      caspase-3 expression, which is indicative of the initiation of apoptosis.
      Cyprodinil was the most toxic agent individually, although oxidative stress
      related enzyme gene expression increases appeared to demonstrate some degree of
      synergy in the presence of the combination of agents. This report suggests that
      the impact of some pesticides, both individually and in combinations, merits
      further study in terms of their impact on human cellular health.

PMID- 22880101
TI  - Neuromorphic atomic switch networks.
AB  - Efforts to emulate the formidable information processing capabilities of the
      brain through neuromorphic engineering have been bolstered by recent progress in
      the fabrication of nonlinear, nanoscale circuit elements that exhibit synapse
      like operational characteristics. However, conventional fabrication techniques
      are unable to efficiently generate structures with the highly complex
      interconnectivity found in biological neuronal networks. Here we demonstrate the
      physical realization of a self-assembled neuromorphic device which implements
      basic concepts of systems neuroscience through a hardware-based platform
      comprised of over a billion interconnected atomic-switch inorganic synapses
      embedded in a complex network of silver nanowires. Observations of network
      activation and passive harmonic generation demonstrate a collective response to
      input stimulus in agreement with recent theoretical predictions. Further,
      emergent behaviors unique to the complex network of atomic switches and akin to
      brain function are observed, namely spatially distributed memory, recurrent
      dynamics and the activation of feedforward subnetworks. These devices display the
      functional characteristics required for implementing unconventional, biologically
      and neurally inspired computational methodologies in a synthetic experimental
      system.

PMID- 22880102
TI  - Transcriptional activation of the human CD2AP promoter by E2F1.
AB  - CD2-associated protein (CD2AP) is an adaptor molecule involved in T cell receptor
      signaling and podocyte homeostasis. CD2AP-deficient mice develop nephritic
      syndrome and renal failure caused by glomerulosclerosis. Transcription factor
      E2F1 is a key regulator of cell proliferation and apoptosis. Here we report that
      E2F1 up-regulates the human CD2AP promoter and further increases the mRNA and
      protein levels of the human CD2AP in human embryonic kidney (HEK) 293 cells. By
      semi-quantitative RT-PCR and Western blot analysis we demonstrate that ectopic
      expression of E2F1 elevates the mRNA and protein levels of CD2AP. Consistently,
      transient transfection assays prove that overexpression of E2F1 transactivates
      the CD2AP promoter while knocking-down of endogenous E2F1 by a shRNA strategy
      results in reduction of the CD2AP promoter activity. Toward understanding the
      underlying mechanism of this regulation, we performed chromatin
      immunoprecipitation and mutations of the putative Sp1 binding sites,
      demonstrating that E2F1 can bind to Sp1 binding site and overexpression of E2F1
      is capable of increasing the binding of E2F1 and decreasing the binding of Sp1 to
      Sp1 binding sites.

PMID- 22880103
TI  - Structural insights into the assembly of CARMA1 and BCL10.
AB  - The CBM complex (CARMA1, BCL10 and MALT1) plays a crucial role in B and T
      lymphocyte activation. CARMA1 serves as a scaffold for BCL10, MALT1 and other
      effector proteins and regulates various signaling pathways related to the immune
      response. The assembly of CARMA1 and BCL10 is mediated through a CARD-CARD
      interaction. Here, we report the crystal structure of the CARD domain of CARMA1
      at a resolution of 1.75 A. The structure consists of six helices, as previously
      determined for CARD domains. Structural and computational analysis identified the
      binding interface between CARMA1-CARD and BCL10-CARD, which consists of a basic
      patch in CARMA1 and an acidic patch in BCL10. Site-directed mutagenesis, co
      immunoprecipitation and an NF-kappaB activation assay confirmed that the
      interface is necessary for association and downstream signaling. Our studies
      provide molecular insight into the assembly of CARMA1 and BCL10.

PMID- 22880104
TI  - Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic
      humanized mice after infection with HIV-1.
AB  - Humanized mice are expected to be useful as small animal models for in vivo
      studies on the pathogenesis of infectious diseases. However, it is well known
      that human CD8(+) T cells cannot differentiate into effector cells in
      immunodeficient mice transplanted with only human CD34(+) hematopoietic stem
      cells (HSCs), because human T cells are not educated by HLA in the mouse thymus.
      We here established HLA-B*51:01 transgenic humanized mice by transplanting human
      CD34(+) HSCs into HLA-B*51:01 transgenic NOD/SCID/Jak3(-/-) mice (hNOK/B51Tg
      mice) and investigated whether human effector CD8(+) T cells would be elicited in
      the mice or in those infected with HIV-1 NL4-3. There were no differences in the
      frequency of late effector memory and effector subsets (CD27(low)CD28(-)CD45RA(+/
      )CCR7(-) and CD27(-)CD28(-)CD45RA(+/-)CCR7(-), respectively) among human CD8(+) T
      cells and in that of human CD8(+) T cells expressing CX3CR1 and/or CXCR1 between
      hNOK/B51Tg and hNOK mice. In contrast, the frequency of late effector memory and
      effector CD8(+) T cell subsets and of those expressing CX3CR1 and/or CXCR1 was
      significantly higher in HIV-1-infected hNOK/B51Tg mice than in uninfected ones,
      whereas there was no difference in that of these subsets between HIV-1-infected
      and uninfected hNOK mice. These results suggest that hNOK/B51Tg mice had CD8(+) T
      cells that were capable of differentiating into effector T cells after viral
      antigen stimulation and had a greater ability to elicit effector CD8(+) T cells
      than hNOK ones.

PMID- 22880105
TI  - Transcriptomic analysis of circulating leukocytes reveals novel aspects of the
      host systemic inflammatory response to sheep scab mites.
AB  - Infestation of ovine skin with the ectoparasitic mite Psoroptes ovis results in
      the development of a rapid cutaneous inflammatory response, leading to the
      crusted skin lesions characteristic of sheep scab. To facilitate the
      identification of novel diagnostic and therapeutic targets, a better
      understanding of the host-parasite relationship in sheep scab is essential.
      Although our knowledge of the host's local cutaneous inflammatory response to
      sheep scab has increased in recent years, we still know relatively little about
      the mechanisms of this response at the systemic level. This study used a combined
      network and pathway analysis of the in vivo transcriptomic response of
      circulating leukocytes to infestation with P. ovis, during a 6 week period.
      Network graph analysis identified six temporally-associated gene clusters, which
      separated into two distinct sub-networks within the graph, representing those
      genes either up or down-regulated during the time course. Functional and pathway
      analysis of these clusters identified novel insights into the host systemic
      response to P. ovis infestation, including roles for the complement system,
      clotting cascade and fibrinolysis. These analyses also highlighted potential
      mechanisms by which the systemic immune response to sheep scab can influence
      local tissue responses via enhanced leukocyte activation and extravasation. By
      analysing the transcriptomic responses of circulating leukocytes in sheep
      following infestation with P. ovis, this study has provided key insights into the
      inflammatory response to infestation and has also demonstrated the utility of
      these cells as a proxy of events occurring at local tissue sites, providing
      insight into the mechanisms by which a local allergen-induced inflammatory
      response may be controlled.

PMID- 22880106
TI  - Syntaxin4 interacting protein (Synip) binds phosphatidylinositol (3,4,5)
      triphosphate.
AB  - The insulin responsive Glut4 transport vesicles contain the v-SNARE protein Vamp2
      that associate with the plasma membrane t-SNARE protein Syntaxin 4 to drive
      insulin-stimulated Glut4 translocation in skeletal muscle and adipocytes. The
      syntaxin 4 interacting protein (Synip) binds to syntaxin 4 in the basal state and
      dissociates in the insulin-stimulated state allowing for the subsequent binding
      of Vamp2 containing Glut4 vesicles and fusion with the plasma membrane. In this
      study, we have found that Synip binds phosphatidylinositol 3,4,5-triphosphate
      (PIP3), but not phosphatidylinositol 3 phosphate (PIP) or phosphatidylinositol
      3,4-biphosphate (PIP2) through the Synip WW domain as deletion of this domain
      (Synip DeltaWW) failed to bind PIP3. Over-expressed Synip DeltaWW in 3T3L1
      adipocytes reduced the basal levels of Glut4 at the plasma membrane with no
      effect on the binding to syntaxin 4 in vitro. Subcellular fractionation
      demonstrated that the amount of Synip DeltaWW at the PM was decreased in response
      to insulin in 3T3L1 adipocytes whereas the amount of Synip WT increased. These
      data suggest that in the presence of insulin, the dissociated Synip remains
      anchored to the plasma membrane by binding to PIP3.

PMID- 22880108
TI  - The effect of exercise training modality on serum brain derived neurotrophic
      factor levels in individuals with type 2 diabetes.
AB  - INTRODUCTION: Brain derived neurotrophic factor (BDNF) has been implicated in
      memory, learning, and neurodegenerative diseases. However, the relationship of
      BDNF with cardiometabolic risk factors is unclear, and the effect of exercise
      training on BDNF has not been previously explored in individuals with type 2
      diabetes. METHODS: Men and women (N = 150) with type 2 diabetes were randomized
      to an aerobic exercise (aerobic), resistance exercise (resistance), or a
      combination of both (combination) for 9 months. Serum BDNF levels were evaluated
      at baseline and follow-up from archived blood samples. RESULTS: Baseline serum
      BDNF was not associated with fitness, body composition, anthropometry, glucose
      control, or strength measures (all, p>0.05). Similarly, no significant change in
      serum BDNF levels was observed following exercise training in the aerobic (
      1649.4 pg/ml, CI: -4768.9 to 1470.2), resistance (-2351.2 pg/ml, CI:-5290.7 to
      588.3), or combination groups (-827.4 pg/ml, CI: -3533.3 to 1878.5) compared to
      the control group (-2320.0 pg/ml, CI: -5750.8 to 1110.8). However, reductions in
      waist circumference were directly associated with changes in serum BDNF following
      training (r = 0.25, p = 0.005). CONCLUSIONS: Serum BDNF was not associated with
      fitness, body composition, anthropometry, glucose control, or strength measures
      at baseline. Likewise, serum BDNF measures were not altered by 9 months of
      aerobic, resistance, or combination training. However, reductions in waist
      circumference were associated with decreased serum BDNF levels. Future studies
      should investigate the relevance of BDNF with measures of cognitive function
      specifically in individuals with type-2 diabetes.

PMID- 22880107
TI  - High basal activity of the PTPN22 gain-of-function variant blunts leukocyte
      responsiveness negatively affecting IL-10 production in ANCA vasculitis.
AB  - Consequences of expression of the protein tyrosine phosphatase nonreceptor 22
      (PTPN22) gain-of-function variant were evaluated in leukocytes from patients with
      anti-neutrophil cytoplasmic autoantibody (ANCA) disease. The frequency of the
      gain-of-function allele within the Caucasian patient cohort was 22% (OR 1.45),
      compared to general American Caucasian population (16.5%, p = 0.03). Examination
      of the basal phosphatase activity of PTPN22 gain-of-function protein indicated
      persistently elevated activity in un-stimulated peripheral leukocytes, while
      basal activity was undetectable in leukocytes from patients without the gain-of
      function variant. To examine consequences of persistently high PTPN22 activity,
      the activation status of ERK and p38 MAPK were analyzed. While moderate levels of
      activated ERK were observed in controls, it was undetectable in leukocytes
      expressing PTPN22 gain-of-function protein and instead p38MAPK was up-regulated.
      IL-10 transcription, reliant on the ERK pathway, was negatively affected. Over
      the course of disease, patients expressing variant PTPN22 did not show a spike in
      IL-10 transcription as they entered remission in contrast to controls, implying
      that environmentally triggered signals were blunted. Sustained activity of
      PTPN22, due to the gain-of-function mutation, acts as a dominant negative
      regulator of ERK activity leading to blunted cellular responsiveness to
      environmental stimuli and expression of protective cytokines.

PMID- 22880109
TI  - Cross border comparison of MRSA bacteraemia between The Netherlands and North
      Rhine-Westphalia (Germany): a cross-sectional study.
AB  - BACKGROUND: We describe the impact of methicillin-resistant Staphylococcus aureus
      (MRSA) in two neighbouring regions in Europe with a comparable population size,
      North Rhine-Westphalia (NRW) in Germany and the Netherlands.
      METHODOLOGY/PRINCIPAL FINDINGS: We compared the occurrence of MRSA in blood
      cultures from surveillance systems. In the Netherlands in 2009, 14 of 1,510
      (0.9%) Staphylococcus aureus bacteraemia episodes under surveillance were MRSA.
      Extrapolation using the number of clinical admissions results in a total of 29
      MRSA bacteraemia episodes in the Netherlands or 1.8 episodes per 1,000,000
      inhabitants. In 2010 in NRW, 1,029 MRSA bacteraemias were reported, resulting in
      57.6 episodes of MRSA bacteraemia per 1,000,000 inhabitants: a 32-fold higher
      incidence than in the Netherlands. CONCLUSION/SIGNIFICANCE: Based on an estimated
      attributable mortality of 15%, the Dutch approach would save approximately 150
      lives per year by the prevention of bacteraemia only.

PMID- 22880110
TI  - IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal
      gnotobiotic piglet disease model.
AB  - Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in
      children worldwide. The aim of the present work was to evaluate protection
      against rotavirus (RV) diarrhea conferred by the prophylactic administration of
      specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated
      with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated
      from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized
      Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV
      specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization 
      VN- titer = 256) for 9 days conferred full protection against Wa HRV associated
      diarrhea and significantly reduced virus shedding. This protection was dose
      dependent. The oral administration of semi-purified passive IgY Abs from chickens
      did not affect the isotype profile of the pig Ab secreting cell (ASC) responses
      to Wa HRV infection, but it was associated with significantly fewer numbers of
      HRV-specific IgA ASC in the duodenum. We further analyzed the pigs immune
      responses to the passive IgY treatment. The oral administration of IgY Abs
      induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab
      responses to IgY in the intestinal contents of neonatal piglets in a dose
      dependent manner. To our knowledge, this is the first study to show that IgY Abs
      administered orally as a milk supplement passively protect neonatal pigs against
      an enteric viral pathogen (HRV). Piglets are an animal model with a
      gastrointestinal physiology and an immune system that closely mimic human
      infants. This strategy can be scaled-up to inexpensively produce large amounts of
      polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic
      passive Ab treatment to control RV diarrhea.

PMID- 22880111
TI  - Decreased expression of vitamin D receptors in neointimal lesions following
      coronary artery angioplasty in atherosclerotic swine.
AB  - BACKGROUND: Inflammatory cytokines, such as TNF-alpha, play a key role in the
      pathogenesis of occlusive vascular diseases. Activation of vitamin D receptors
      (VDR) elicits both growth-inhibitory and anti-inflammatory effects. Here, we
      investigated the expression of TNF-alpha and VDR in post-angioplasty coronary
      artery neointimal lesions of hypercholesterolemic swine and examined the effect
      of vitamin D deficiency on the development of coronary restenosis. We also
      examined the effect of calcitriol on cell proliferation and effect of TNF-alpha
      on VDR activity and expression in porcine coronary artery smooth muscle cells
      (PCASMCs) in-vitro. METHODOLOGY/PRINCIPAL FINDINGS: Expression of VDR and TNF
      alpha and the effect of vitamin D deficiency in post-angioplasty coronary
      arteries were analyzed by immunohistochemistry and histomorphometry. Cell
      proliferation was examined by thymidine and BrdU incorporation assays in cultured
      PCASMCs. Effect of TNF-alpha-stimulation on the activity and expression of VDR
      was analyzed by luciferase assay, immunoblotting and immunocytochemistry. In
      vivo, morphometric analysis of the tissues revealed typical lesions with
      significant neointimal proliferation. Histological evaluation showed expression
      of smooth muscle alpha-actin and significantly increased expression of TNF-alpha
      in neointimal lesions. Interestingly, there was significantly decreased
      expression of VDR in PCASMCs of neointimal region compared to normal media.
      Indeed, post-balloon angioplasty restenosis was significantly higher in vitamin D
      deficient hypercholesterolemic swine compared to vitamin D-sufficient group. In
      vitro, calcitriol inhibited both serum- and PDGF-BB-induced proliferation in
      PCASMCs and TNF-alpha-stimulation significantly decreased the expression and
      activity of VDR in PCASMCs. CONCLUSIONS/SIGNIFICANCE: These data suggest that
      significant downregulation of VDR in proliferating smooth muscle cells in
      neointimal lesions could be due to atherogenic cytokines, including TNF-alpha.
      Vitamin D deficiency potentiates the development of coronary restenosis.
      Calcitriol has anti-proliferative properties in PCASMCs and these actions are
      mediated through VDR. This could be a potential mechanism for uncontrolled growth
      of neointimal cells in injured arteries leading to restenosis.

PMID- 22880112
TI  - Treatment-related death in patients with small-cell lung cancer in phase III
      trials over the last two decades.
AB  - INTRODUCTION: Treatment-related death (TRD) remains a serious problem in small
      cell lung cancer (SCLC), despite recent improvements in supportive care. However,
      few studies have formally assessed time trends in the proportion of TRD over the
      past two decades. The aim of this study was to determine the frequency and
      pattern of TRD over time. METHODS: We examined phase 3 trials conducted between
      1990 and 2010 to address the role of systemic treatment for SCLC. The time trend
      was assessed using linear regression analysis. RESULTS: In total, 97 trials
      including nearly 25,000 enrolled patients were analyzed. The overall TRD
      proportion was 2.95%. Regarding the time trend, while it was not statistically
      significant, it tended to decrease, with a 0.138% decrease per year and 2.76%
      decrease per two decades. The most common cause of death was febrile neutropenia
      without any significant time trend in its incidence over the years examined (p =
      0.139). However, deaths due to febrile neutropenia as well as all causes in
      patients treated with non-platinum chemotherapy increased significantly (p =
      0.033). CONCLUSIONS: The overall TRD rate has been low, but not negligible, in
      phase III trials for SCLC over the past two decades.

PMID- 22880113
TI  - Functional neuronal cells generated by human parthenogenetic stem cells.
AB  - Parent of origin imprints on the genome have been implicated in the regulation of
      neural cell type differentiation. The ability of human parthenogenetic (PG)
      embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific
      differentiation is undefined. We determined the potential of hpESCs to
      differentiate into various neural subtypes. Concurrently, we examined DNA
      methylation and expression status of imprinted genes. Under culture conditions
      promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave
      rise to glia and neuron-like cells that expressed subtype-specific markers and
      generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs
      revealed that maternal-specific gene expression patterns and imprinting marks
      were generally maintained in PG cells upon differentiation. Our results
      demonstrate that despite the lack of a paternal genome, hpESCs generate
      proliferating NSCs that are capable of differentiation into physiologically
      functional neuron-like cells and maintain allele-specific expression of imprinted
      genes. Thus, hpESCs can serve as a model to study the role of maternal and
      paternal genomes in neural development and to better understand imprinting
      associated brain diseases.

PMID- 22880114
TI  - Rat bone marrow-derived Schwann-like cells differentiated by the optimal inducers
      combination on microfluidic chip and their functional performance.
AB  - Numerous researches demonstrated the possibility of derivation of Schwann-like
      (SC-like) cells in vitro from bone marrow stromal cells (BMSCs). However, the
      concentration of the induce factors were different in those studies, especially
      for the critical factors forskolin (FSK) and beta-heregulin (HRG). Here, we used
      a new and useful method to build an integrated microfluidic chip for rapid
      analyses of the optimal combination between the induce factors FSK and HRG. The
      microfluidic device was mainly composed of an upstream concentration gradient
      generator (CGG) and a downstream cell culture module. Rat BMSCs were cultured in
      the cell chambers for 11 days at the different concentrations of induce factors
      generated by CGG. The result of immunofluorescence staining on-chip showed that
      the group of 4.00 uM FSK and 250.00 ng/ml HRG presented an optimal effect to
      promote the derivation of SC-like cells. Moreover, the optimal SC-like cells
      obtained on-chip were further tested using DRG co-culture and ELISA to detect
      their functional performance. Our findings demonstrate that SC-like cells could
      be obtained with high efficiency and functional performance in the optimal
      inducers combination.

PMID- 22880116
TI  - The cortical signature of amyotrophic lateral sclerosis.
AB  - The aim of this study was to explore the pattern of regional cortical thickness
      in patients with non-familial amyotrophic lateral sclerosis (ALS) and to
      investigate whether cortical thinning is associated with disease progression
      rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy
      controls. Group differences in cortical thickness and the age-by-group effects
      were assessed using vertex-by-vertex and multivariate linear models. The
      discriminatory ability of MRI variables in distinguishing patients from controls
      was estimated using the Concordance Statistics (C-statistic) within logistic
      regression analyses. Correlations between cortical thickness measures and disease
      progression rate were tested using the Pearson coefficient. Relative to controls,
      ALS patients showed a bilateral cortical thinning of the primary motor,
      prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and
      inferior temporal and parietal regions, and medial and lateral occipital areas.
      There was a significant age-by-group effect in the sensorimotor cortices
      bilaterally, suggesting a stronger association between age and cortical thinning
      in ALS patients compared to controls. The mean cortical thickness of the
      sensorimotor cortices distinguished patients with ALS from controls (C-statistic
      >= 0.74). Cortical thinning of the left sensorimotor cortices was related to a
      faster clinical progression (r = -0.33, p = 0.03). Cortical thickness
      measurements allowed the detection and quantification of motor and extramotor
      involvement in patients with ALS. Cortical thinning of the precentral gyrus might
      offer a marker of upper motor neuron involvement and disease progression.

PMID- 22880115
TI  - CXC chemokine receptor 7 (CXCR7) regulates CXCR4 protein expression and capillary
      tuft development in mouse kidney.
AB  - BACKGROUND: The CXCL12/CXCR4 axis is involved in kidney development by regulating
      formation of the glomerular tuft. Recently, a second CXCL12 receptor was
      identified and designated CXCR7. Although it is established that CXCR7 regulates
      heart and brain development in conjunction with CXCL12 and CXCR4, little is known
      about the influence of CXCR7 on CXCL12 dependent kidney development.
      METHODOLOGY/PRINCIPAL FINDINGS: We provided analysis of CXCR7 expression and
      function in the developing mouse kidney. Using in situ hybridization, we
      identified CXCR7 mRNA in epithelial cells including podocytes at all nephron
      stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with
      CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal
      cells and the glomerular tuft. Expression of CXCR4 was complementary to that of
      CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and
      glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7
      null mice revealed ballooning of glomerular capillaries as described earlier for
      CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but
      not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme.
      Malformation of the glomerular tuft in CXCR7 null mice was associated with
      mesangial cell clumping. CONCLUSIONS/SIGNIFICANCE: We established that there is a
      similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the
      phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the
      forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated
      signalling between podocytes and glomerular capillaries.

PMID- 22880117
TI  - Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's
      disease.
AB  - Although deep brain stimulation (DBS) of the basal ganglia improves motor
      outcomes in Parkinson's disease (PD), its effects on cognition, including
      language, remain unclear. This study examined the impact of subthalamic nucleus
      (STN) DBS on two fundamental capacities of language, grammatical and lexical
      functions. These functions were tested with the production of regular and
      irregular past-tenses, which contrast aspects of grammatical (regulars) and
      lexical (irregulars) processing while controlling for multiple potentially
      confounding factors. Aspects of the motor system were tested by contrasting the
      naming of manipulated (motor) and non-manipulated (non-motor) objects.
      Performance was compared between healthy controls and early-stage PD patients
      treated with either DBS/medications or medications alone. Patients were assessed
      on and off treatment, with controls following a parallel testing schedule. STN
      DBS improved naming of manipulated (motor) but not non-manipulated (non-motor)
      objects, as compared to both controls and patients with just medications, who did
      not differ from each other across assessment sessions. In contrast, STN-DBS led
      to worse performance at regulars (grammar) but not irregulars (lexicon), as
      compared to the other two subject groups, who again did not differ. The results
      suggest that STN-DBS negatively impacts language in early PD, but may be specific
      in depressing aspects of grammatical and not lexical processing. The finding that
      STN-DBS affects both motor and grammar (but not lexical) functions strengthens
      the view that both depend on basal ganglia circuitry, although the mechanisms for
      its differential impact on the two (improved motor, impaired grammar) remain to
      be elucidated.

PMID- 22880118
TI  - Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii
      cells to fluconazole.
AB  - Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in
      immunocompetent humans and animals. As current antifungal therapies are few and
      limited in efficacy, and resistance is an emerging issue, the development of new
      treatment strategies is urgently required. The current study undertook a time
      course analysis of the proteome of C. gattii during treatment with fluconazole
      (FLC), which is used widely in prophylactic and maintenance therapies. The aims
      were to analyze the overall cellular response to FLC, and to find fungal proteins
      involved in this response that might be useful targets in therapies that augment
      the antifungal activity of FLC. During FLC treatment, an increase in stress
      response, ATP synthesis and mitochondrial respiratory chain proteins, and a
      decrease in most ribosomal proteins was observed, suggesting that ATP-dependent
      efflux pumps had been initiated for survival and that the maintenance of ribosome
      synthesis was differentially expressed. Two proteins involved in fungal specific
      pathways were responsive to FLC. An integrative network analysis revealed co
      ordinated processes involved in drug response, and highlighted hubs in the
      network representing essential proteins that are required for cell viability.
      This work demonstrates the dynamic cellular response of a typical susceptible
      isolate of C. gattii to FLC, and identified a number of proteins and pathways
      that could be targeted to augment the activity of FLC.

PMID- 22880119
TI  - Localization of acetylcholine-related molecules in the retina: implication of the
      communication from photoreceptor to retinal pigment epithelium.
AB  - It has been long speculated that specific signals are transmitted from
      photoreceptors to the retinal pigment epithelium (RPE). However, such signals
      have not been identified. In this study, we examined the retinal expression and
      localization of acetylcholine-related molecules as putative candidates for these
      signals. Previous reports revealed that alpha7 nicotinic acetylcholine receptors
      (nAChRs) are present in the microvilli of RPE cells that envelope the tips of
      photoreceptor outer segments (OS). Secreted mammalian leukocyte antigen
      6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) is a
      positive allosteric modulator of the alpha7 nAChR. Therefore, we first focused on
      the expression of SLURP-1. SLURP-1 mRNA was expressed in the outer nuclear layer,
      which is comprised of photoreceptor cell bodies. SLURP-1 immunoreactivity co
      localized with rhodopsin and S-opsin in photoreceptor OS, while choline
      acetyltransferase (ChAT) and high affinity choline transporter (CHT-1) were also
      expressed in photoreceptor OS. Immunoelectron microscopy identified that the
      majority of SLURP-1 was localized to the plasma membranes of photoreceptor OS.
      These results provide evidence that SLURP-1 is synthesized in photoreceptor cell
      bodies and transported to photoreceptor OS, where SLURP-1 may also be secreted.
      Our findings suggest that photoreceptor OS communicate via neurotransmitters such
      as ACh and SLURP-1, while RPE cells might receive these signals through alpha7
      nAChRs in their microvilli.

PMID- 22880120
TI  - Failure to eradicate Isospora belli diarrhoea despite immune reconstitution in
      adults with HIV--a case series.
AB  - Isospora belli causes diarrhoea in patients with AIDS. Most respond to targeted
      therapy and recommendations are that secondary prophylaxis can be stopped
      following immune reconstitution with ART. We report eight cases of chronic
      isosporiasis that persisted despite standard antimicrobial therapy, secondary
      prophylaxis, and good immunological and virological response to ART. Median CD4
      nadir was 175.5 cells/mm(3) and median highest CD4 while symptomatic was 373
      cells/mm(3). Overall 34% of stool samples and 63% of duodenal biopsy specimens
      were positive for oocytes. Four patients died, two remain symptomatic and two
      recovered. Possible explanations for persistence of symptoms include host factors
      such as antigen specific immune deficiency or generalised reduction in gut
      immunity. Parasite factors may include accumulating resistance to co-trimoxazole.
      Research is required to determine the optimum dose and duration of co-trimoxazole
      therapy and whether dual therapy may be necessary. Mortality was high and pending
      more data we recommend extended treatment with high-dose co-trimoxazole in
      similar cases.

PMID- 22880121
TI  - Functional gene-guided discovery of type II polyketides from culturable
      actinomycetes associated with soft coral Scleronephthya sp.
AB  - Compared with the actinomycetes in stone corals, the phylogenetic diversity of
      soft coral-associated culturable actinomycetes is essentially unexplored.
      Meanwhile, the knowledge of the natural products from coral-associated
      actinomycetes is very limited. In this study, thirty-two strains were isolated
      from the tissue of the soft coral Scleronephthya sp. in the East China Sea, which
      were grouped into eight genera by 16S rDNA phylogenetic analysis: Micromonospora,
      Gordonia, Mycobacterium, Nocardioides, Streptomyces, Cellulomonas, Dietzia and
      Rhodococcus. 6 Micromonospora strains and 4 Streptomyces strains were found to be
      with the potential for producing aromatic polyketides based on the analysis of
      KS(alpha) (ketoacyl-synthase) gene in the PKS II (type II polyketides synthase)
      gene cluster. Among the 6 Micromonospora strains, angucycline cyclase gene was
      amplified in 2 strains (A5-1 and A6-2), suggesting their potential in
      synthesizing angucyclines e.g. jadomycin. Under the guidance of functional gene
      prediction, one jadomycin B analogue (7b, 13-dihydro-7-O-methyl jadomycin B) was
      detected in the fermentation broth of Micromonospora sp. strain A5-1. This study
      highlights the phylogenetically diverse culturable actinomycetes associated with
      the tissue of soft coral Scleronephthya sp. and the potential of coral-derived
      actinomycetes especially Micromonospora in producing aromatic polyketides.

PMID- 22880122
TI  - IL-10 mediated regulation of liver inflammation during acute murine
      cytomegalovirus infection.
AB  - Various cell types in both lymphoid and non-lymphoid tissues produce the anti
      inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV)
      infection. The functions of IL-10 in the liver during acute infection and the
      cells that generate this cytokine at this site have not been extensively
      investigated. In this study, we demonstrate that the production of IL-10 in the
      liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10
      green fluorescence protein (GFP) reporter knock-in mice, designated IL-10
      internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are
      identified as major IL-10 expressing cells in the liver after infection, along
      with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked
      elevations in proinflammatory cytokines and in the numbers of mononuclear cells
      and lymphocytes infiltrating the liver during this infection. IL-10-deficiency
      also enhances liver injury without improving viral clearance from this site.
      Collectively, the results indicate that IL-10-producing cells in the liver
      provide protection from collateral injury by modulating the inflammatory response
      associated with MCMV infection.

PMID- 22880123
TI  - Indoor residual spraying of insecticide and malaria morbidity in a high
      transmission intensity area of Uganda.
AB  - BACKGROUND: Recently the use of indoor residual spraying of insecticide (IRS) has
      greatly increased in Africa; however, limited data exist on the quantitative
      impacts of IRS on health outcomes in highly malaria endemic areas.
      METHODOLOGY/PRINCIPAL FINDINGS: Routine data were collected on more than 90,000
      patient visits at a single health facility over a 56 month period covering five
      rounds of IRS using three different insecticides. Temporal associations between
      the timing of IRS and the probability of a patient referred for microscopy having
      laboratory confirmed malaria were estimated controlling for seasonality and age.
      Considering patients less than five years of age there was a modest decrease in
      the odds of malaria following the 1(st) round of IRS using DDT (OR = 0.76,
      p<0.001) and the 2(nd) round using alpha-cypermethrin (OR = 0.83, p = 0.002).
      Following rounds 3-5 using bendiocarb there was a much greater decrease in the
      odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons).
      Overall, the impact of IRS was less pronounced among patients 5 years or older.
      CONCLUSIONS/SIGNIFICANCE: IRS was associated with a reduction in malaria
      morbidity in an area of high transmission intensity in Uganda and the benefits
      appeared to be greatest after switching to a carbamate class of insecticide.

PMID- 22880124
TI  - Seroprevalence of measles-, mumps- and rubella-specific IgG antibodies in German
      children and adolescents and predictors for seronegativity.
AB  - We have undertaken a seroprevalence study with more than 13,000 children, who had
      been included in the German KIGGS survey, a representative sample of children and
      adolescents 0-17 years of age. The IgG titres against measles, mumps and rubella
      were determined in 1 to 17 year olds While 88.8% of the children were MMR
      vaccinated at least once, 76.8% of children aged 1 to 17 years showed prevalence
      of antibodies to MMR. The highest seronegativity was seen with respect to mumps.
      Gender differences were most pronounced with regard to rubella IgG titres: girls
      aged 14 to 17 years were best protected, although seronegativity in 6.8% of this
      vulnerable group still shows the need of improvement. Search for predictors of
      missing seroprevalence identified young age to be the most important predictor.
      Children living in the former West and children born outside of Germany had a
      higher risk of lacking protection against measles and rubella, while children
      with a migration background but born in Germany were less often seronegative to
      measles antibodies than their German contemporaries. An association of
      seronegativity and early vaccination was seen for measles but not for mumps and
      rubella. A high maternal educational level was associated with seronegativity to
      measles and rubella. In vaccinated children, seronegativity was highest for mumps
      and lowest for rubella. For mumps, high differences were observed for
      seronegativity after one-dose and two-dose vaccination, respectively.
      Seronegativity increases as time since last vaccination passes thus indicating
      significant waning effects for all three components of MMR.

PMID- 22880125
TI  - Uncoupling the effects of seed predation and seed dispersal by granivorous ants
      on plant population dynamics.
AB  - Secondary seed dispersal is an important plant-animal interaction, which is
      central to understanding plant population and community dynamics. Very little
      information is still available on the effects of dispersal on plant demography
      and, particularly, for ant-seed dispersal interactions. As many other
      interactions, seed dispersal by animals involves costs (seed predation) and
      benefits (seed dispersal), the balance of which determines the outcome of the
      interaction. Separate quantification of each of them is essential in order to
      understand the effects of this interaction. To address this issue, we have
      successfully separated and analyzed the costs and benefits of seed dispersal by
      seed-harvesting ants on the plant population dynamics of three shrub species with
      different traits. To that aim a stochastic, spatially-explicit individually-based
      simulation model has been implemented based on actual data sets. The results from
      our simulation model agree with theoretical models of plant response dependent on
      seed dispersal, for one plant species, and ant-mediated seed predation, for
      another one. In these cases, model predictions were close to the observed values
      at field. Nonetheless, these ecological processes did not affect in anyway a
      third species, for which the model predictions were far from the observed values.
      This indicates that the balance between costs and benefits associated to
      secondary seed dispersal is clearly related to specific traits. This study is one
      of the first works that analyze tradeoffs of secondary seed dispersal on plant
      population dynamics, by disentangling the effects of related costs and benefits.
      We suggest analyzing the effects of interactions on population dynamics as
      opposed to merely analyzing the partners and their interaction strength.

PMID- 22880126
TI  - Identification of DNA binding motifs of the Mycobacterium tuberculosis PhoP/PhoR
      two-component signal transduction system.
AB  - BACKGROUND: The Mycobacterium tuberculosis PhoP/PhoR two-component signal
      transduction system controls the expression of about 2% of the genome and plays a
      major role in pathogenicity. However, its regulon has not been well
      characterized. METHODOLOGY/PRINCIPAL FINDINGS: The binding site of PhoP
      transcription regulator was identified in the upstream regions of msl3, pks2,
      lipF and fadD21 genes, by using gene fusions, electrophoretic mobility shift
      assays and DNase I footprinting experiments. A consensus sequence for PhoP
      binding was deduced. It consists of two direct repeats, DR1/DR2, associated with
      a third repeat, DR3, important in some cases for PhoP binding to DR1/DR2 but
      located at a variable distance from these direct repeats. DR1/DR2 and DR3
      consensus sequences were used to screen the whole-genome sequence for other
      putative binding sites potentially corresponding to genes directly regulated by
      PhoP. The identified 87 genes, encoding transcription regulators, and proteins
      involved in secondary metabolites biosynthesis, transport and catabolism are
      proposed to belong to the PhoP regulon. CONCLUSIONS/SIGNIFICANCE: A consensus
      sequence derived from the analysis of PhoP binding to four gene promoter regions
      is proposed. We show for the first time the involvement of a third direct repeat
      motif in this binding reaction. The consensus sequence was instrumented to study
      the global regulation mediated by PhoP in M. tuberculosis. This analysis leads to
      the identification of several genes that are potentially regulated by this key
      player.

PMID- 22880127
TI  - Contributions of renin-angiotensin system-related gene interactions to obesity in
      a Chinese population.
AB  - BACKGROUND: Gene-gene interactions may be partly responsible for complex traits
      such as obesity. Increasing evidence suggests that the renin-angiotensin system
      (RAS) contributes to the etiology of obesity. How the epistasis of genes in the
      RAS contributes to obesity is still under research. We aim to evaluate the
      contribution of RAS-related gene interactions to a predisposition of obesity in a
      Chinese population. METHODOLOGY AND PRINCIPAL FINDINGS: We selected six single
      nucleotide polymorphisms (SNPs) located in angiotensin (AGT), angiotensin
      converting enzyme (ACE), angiotensin type 1 receptor (AGTR1), MAS1, nitric oxide
      synthase 3 (NOS3) and the bradykinin B2 receptor gene (BDKRB2), and genotyped
      them in 324 unrelated individuals with obesity (BMI >= 28 kg/m(2)) and 373 non
      obese controls (BMI 18.5 to <24 kg/m(2)) from a large scale population-based
      cohort. We analyzed gene-gene interactions among 6 polymorphic loci using the
      Generalized Multifactor Dimensionality Reduction (GMDR) method, which has been
      shown to be effective for detecting gene-gene interactions in case-control
      studies with relatively small samples. Then we used logistic regression models to
      confirm the best combination of loci identified in the GMDR. It showed a
      significant gene-gene interaction between the rs220721 polymorphism in the MAS1
      gene and the rs1799722 polymorphism in the gene BDKB2R. The best two-locus
      combination scored 9 for cross-validation consistency and 9 for sign test (p =
      0.0107). This interaction showed the maximum consistency and minimum prediction
      error among all gene-gene interaction models evaluated. Moreover, the combination
      of the MAS1 rs220721 and the BDKRB2 rs1799722 was associated with a significantly
      increased risk of obesity (OR 1.82, CI 95%: 1.15-2.88, p = 0.0103). CONCLUSIONS
      AND SIGNIFICANCE: These results suggest that the SNPs from the RAS-related genes
      may contribute to the risk of obesity in an interactive manner in a Chinese
      population. The gene-gene interaction may serve as a novel area for obesity
      research.

PMID- 22880128
TI  - Cell membrane disruption stimulates NO/PKG signaling and potentiates cell
      membrane repair in neighboring cells.
AB  - Resealing of a disrupted plasma membrane at the micron-diameter range requires
      Ca(2+)-regulated exocytosis. Repeated membrane disruptions reseal more quickly
      than the initial wound, and this potentiation of membrane resealing persists for
      at least 24 hours after the initial wound. Long-term potentiation of membrane
      resealing requires CREB-dependent gene expression, which is activated by the PKC-
      and p38 MAPK-dependent pathway in a wounded cell. The present study demonstrates
      that membrane resealing is potentiated in both wounded and neighboring cells in
      MDCK cells. Wounding of cells expressing CREB133, a mutant variant of CREB, does
      not show the potentiated response of cell membrane resealing in either wounded or
      neighboring cells. Furthermore, wounding of cells induces CREB phosphorylation,
      not only in wounded cells, but also in neighboring cells. Inhibition of the
      nitric oxide/PKG signaling pathway suppresses CREB phosphorylation in neighboring
      cells, but not in wounded cells. The potentiation of membrane resealing in
      neighboring cells is suppressed if the nitric oxide/PKG pathway is inhibited
      during the initial wound. Together, these results suggest that the nitric
      oxide/PKG pathway stimulates CREB phosphorylation in neighboring cells so that
      subsequent cell membrane disruptions of the neighboring cells reseal more
      quickly.

PMID- 22880129
TI  - SAP--a sequence mapping and analyzing program for long sequence reads alignment
      and accurate variants discovery.
AB  - The third-generation of sequencing technologies produces sequence reads of 1000
      bp or more that may contain high polymorphism information. However, most
      currently available sequence analysis tools are developed specifically for
      analyzing short sequence reads. While the traditional Smith-Waterman (SW)
      algorithm can be used to map long sequence reads, its naive implementation is
      computationally infeasible. We have developed a new Sequence mapping and
      Analyzing Program (SAP) that implements a modified version of SW to speed up the
      alignment process. In benchmarks with simulated and real exon sequencing data and
      a real E. coli genome sequence data generated by the third-generation sequencing
      technologies, SAP outperforms currently available tools for mapping short and
      long sequence reads in both speed and proportion of captured reads. In addition,
      it achieves high accuracy in detecting SNPs and InDels in the simulated data. SAP
      is available at https://github.com/davidsun/SAP.

PMID- 22880130
TI  - Functional characterization of the small heat shock protein Hsp12p from Candida
      albicans.
AB  - Hsp12p is considered to be a small heat shock protein and conserved among fungal
      species. To investigate the expression of this heat shock protein in the fungal
      pathogen Candida albicans we developed an anti-CaHsp12p antibody. We show that
      this protein is induced during stationary phase growth and under stress
      conditions including heat shock, osmotic, oxidative and heavy metal stress.
      Furthermore, we find that CaHsp12p expression is influenced by the quorum sensing
      molecule farnesol, the change of CO(2) concentration and pH. Notably we show that
      the key transcription factor Efg1p acts as a positive regulator of CaHsp12p in
      response to heat shock and oxidative stress and demonstrate that CaHsp12p
      expression is additionally modulated by Hog1p and the cAMP-PKA signaling pathway.
      To study the function of Hsp12p in C. albicans we generated a null mutant, in
      which all four CaHSP12 genes have been deleted. Phenotypic analysis of the strain
      shows that CaHSP12 is not essential for stress resistance, morphogenesis or
      virulence when tested in a Drosophila model of infection. However, when
      overexpressed, CaHSP12 significantly enhanced cell-cell adhesion, germ tube
      formation and susceptibility to azole antifungal agents whilst desensitizing C.
      albicans to the quorum sensing molecule farnesol.

PMID- 22880131
TI  - c-Myb regulates cell cycle-dependent expression of Erbin: an implication for a
      novel function of Erbin.
AB  - In the present study, we demonstrated the cell cycle periodicity of Erbin
      expression with the maximal expression of Erbin in G2/M phase. A significant
      increase in Erbin promoter activity was observed in G2/M phase-synchronized
      cells. Sequence analysis revealed a c-Myb site in the core promoter region of
      Erbin. Mutagenesis of c-Myb consensus sequences abrogated the increased Erbin
      promoter activity in G2/M phase. ChIP and oligonucleotide pull-down assays
      validated that the recruitment of c-Myb to the consensus sequences was specific.
      The interaction of c-Myb with c-Myb site in the Erbin promoter was significantly
      enhanced in G2/M phase. Ectopic overexpression of c-Myb led to the up-regulation
      of Erbin promoter activity and c-Myb silencing by small interfering RNA
      significantly decreased Erbin protein level. Transfection of c-Myb rescued Erbin
      expression that was impaired by c-Myb knockdown. It proves that c-Myb and the c
      Myb response element mediate the cell cycle-dependent expression of Erbin.
      Inactivation of Erbin causes an acceleration of the G1/S transition, the
      formation of multipolar spindles and abnormal chromosome congression. These
      results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M
      phase and also predict an unappreciated function of Erbin in cell cycle
      progression.

PMID- 22880132
TI  - Curcumin prevents formation of polyglutamine aggregates by inhibiting Vps36, a
      component of the ESCRT-II complex.
AB  - Small molecules with antioxidative properties have been implicated in amyloid
      disorders. Curcumin is the active ingredient present in turmeric and known for
      several biological and medicinal effects. Adequate evidence substantiates the
      importance of curcumin in Alzheimer's disease and recent evidence suggests its
      role in Prion and Parkinson's disease. However, contradictory effects have been
      suggested for Huntington's disease. This difference provided a compelling reason
      to investigate the effect of curcumin on glutamine-rich (Q-rich) and non
      glutamine-rich (non Q-rich) amyloid aggregates in the well established yeast
      model system. Curcumin significantly inhibited the formation of htt72Q-GFP (a Q
      rich) and Het-s-GFP (a non Q-rich) aggregates in yeast. We show that curcumin
      prevents htt72Q-GFP aggregation by down regulating Vps36, a component of the
      ESCRT-II (Endosomal sorting complex required for transport). Moreover, curcumin
      disrupted the htt72Q-GFP aggregates that were pre-formed in yeast and cured the
      yeast prion, [PSI(+)].

PMID- 22880133
TI  - Mood disorders and risk of lung cancer in the EAGLE case-control study and in the
      U.S. Veterans Affairs inpatient cohort.
AB  - BACKGROUND: Mood disorders may affect lung cancer risk. We evaluated this
      hypothesis in two large studies. METHODOLOGY/PRINCIPAL FINDINGS: We examined
      1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in
      Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002-2005),
      and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years
      without a lung cancer diagnosis in the U.S. Veterans Affairs Inpatient Cohort (VA
      study), composed of veterans with a VA hospital admission (1969-1996). In EAGLE,
      we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive
      adjustment for tobacco smoking and multiple lifestyle factors. In the VA study,
      we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent
      Poisson regression, adjusting for attained age, calendar year, hospital visits,
      time within the study, and related previous medical diagnoses. In EAGLE, we found
      decreased lung cancer risk in subjects with a personal history of mood disorders
      (OR: 0.59, 95% CI: 0.44-0.79, based on 121 lung cancer incident cases and 192
      controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50-0.77,
      based on 223 lung cancer cases and 345 controls). The VA study analyses yielded
      similar results (RR: 0.74, 95% CI: 0.71-0.77, based on 2,304 incident lung cancer
      cases and 177,267 non-cancer person-years) in men with discharge diagnoses for
      mood disorders. History of mood disorders was associated with nicotine
      dependence, alcohol and substance use and psychometric scales of depressive and
      anxiety symptoms in controls for these studies. CONCLUSIONS/SIGNIFICANCE: The
      consistent finding of a relationship between mood disorders and lung cancer risk
      across two large studies calls for further research into the complex interplay of
      risk factors associated with these two widespread and debilitating diseases.
      Although we adjusted for smoking effects in EAGLE, residual confounding of the
      results by smoking cannot be ruled out.

PMID- 22880134
TI  - Systemic preconditioning by a prolyl hydroxylase inhibitor promotes prevention of
      skin flap necrosis via HIF-1-induced bone marrow-derived cells.
AB  - BACKGROUND: Local skin flaps often present with flap necrosis caused by critical
      disruption of the blood supply. Although animal studies demonstrate enhanced
      angiogenesis in ischemic tissue, no strategy for clinical application of this
      phenomenon has yet been defined. Hypoxia-inducible factor 1 (HIF-1) plays a
      pivotal role in ischemic vascular responses, and its expression is induced by the
      prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). We assessed whether
      preoperative stabilization of HIF-1 by systemic introduction of DMOG improves
      skin flap survival. METHODS AND RESULTS: Mice with ischemic skin flaps on the
      dorsum were treated intraperitoneally with DMOG 48 hr prior to surgery. The
      surviving area with neovascularization of the ischemic flaps was significantly
      greater in the DMOG-treated mice. Significantly fewer apoptotic cells were
      present in the ischemic flaps of DMOG-treated mice. Interestingly, marked
      increases in circulating endothelial progenitor cells (EPCs) and bone marrow
      proliferative progenitor cells were observed within 48 hr after DMOG treatment.
      Furthermore, heterozygous HIF-1alpha-deficient mice exhibited smaller surviving
      flap areas, fewer circulating EPCs, and larger numbers of apoptotic cells than
      did wild-type mice, while DMOG pretreatment of the mutant mice completely
      restored these parameters. Finally, reconstitution of wild-type mice with the
      heterozygous deficient bone marrow cells significantly decreased skin flap
      survival. CONCLUSION: We demonstrated that transient activation of the HIF
      signaling pathway by a single systemic DMOG treatment upregulates not only anti
      apoptotic pathways but also enhances neovascularization with concomitant increase
      in the numbers of bone marrow-derived progenitor cells.

PMID- 22880136
TI  - Fine retinal striae associated with epiretinal membrane visualized using adaptive
      optics.
AB  - PURPOSE: To describe a case of fine retinal striae visualized using an adaptive
      optics flood illuminated (AO-flood) fundus camera in a patient with vision loss
      from an idiopathic macular epiretinal membrane (ERM). METHODS: A case report of a
      48-year-old woman with recent vision loss from ERM imaged using an AO-flood
      fundus camera and high resolution Fourier-domain optical coherence tomography (Fd
      OCT) before and 3 months after vitrectomy. RESULTS: Visual acuity improved from
      20/70 to 20/20 after vitrectomy. Preoperative Fd-OCT showed severe cystoid
      macular edema with irregularities in the outer nuclear layer which consists of
      cell bodies of photoreceptors. Preoperative AO-flood en face images showed dark
      linear striae of approximately 10 MUm width overlying the cone mosaic that
      improved following surgery, concurrent with improvement in visual acuity and
      morphologic changes on Fd-OCT. CONCLUSION: Microstructural changes within the
      retinal layers resulting from macular traction from ERM can be visualized using
      an AO-flood fundus camera and Fd-OCT. They can appear as fine linear striae in AO
      flood en face images. Further studies are needed to correlate these changes with
      vision loss associated with this condition.

PMID- 22880135
TI  - Staphylococcus aureus ocular infection: methicillin-resistance, clinical
      features, and antibiotic susceptibilities.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is an
      important public health issue. The study aimed to determine the prevalence of
      ocular infections caused by MRSA and to identify the clinical characteristics and
      antibiotic susceptibility of ocular MRSA infections by comparing those of ocular
      methicillin-sensitive S. aureus (MSSA) infections. METHODOLOGY/PRINCIPAL
      FINDINGS: The medical records of the patients (n = 519) with culture-proven S.
      aureus ocular infections seen between January 1, 1999 and December 31, 2008 in
      Chang Gung Memorial Hospital were retrospectively reviewed. Two hundred and
      seventy-four patients with MRSA and 245 with MSSA ocular infections were
      identified. The average rate of MRSA in S. aureus infections was 52.8% and the
      trend was stable over the ten years (P value for trend  = 0.228). MRSA ocular
      infections were significantly more common among the patients with healthcare
      exposure (P = 0.024), but 66.1% (181/274) patients with MRSA ocular infections
      had no healthcare exposure. The most common clinical presentation for both MRSA
      and MSSA ocular infections was keratitis; MRSA and MSSA caused a similar disease
      spectrum except for lid infections. MRSA was significantly more resistant than
      MSSA to clindamycin, erythromycin and sulfamethoxazole/trimethoprim (all
      P<0.001). CONCLUSIONS/SIGNIFICANCE: We demonstrated a paralleled trend of ocular
      MRSA infection in a highly prevalent MRSA country by hospital-based survey.
      Except for lid disorder, MRSA shared similar spectrum of ocular pathology with
      MSSA. Since S. aureus is a common ocular pathogen, our results raise clinician's
      attention to the existence of highly prevalent MRSA.

PMID- 22880137
TI  - Maculopathy diagnosed with high-resolution fourier-domain optical coherence
      tomography in eyes with previously unexplained visual loss.
AB  - PURPOSE: To describe maculopathy diagnosed with high-resolution Fourier-domain
      optical coherence tomography among eyes with previously unexplained visual loss.
      METHODS: Nine eyes from six patients with previously unexplained vision loss
      based on funduscopy, fluorescein angiography, and Stratus optical coherence
      tomography and 32 eyes from 25 asymptomatic age-matched control subjects were
      imaged with a Fourier-domain optical coherence tomography instrument with axial
      resolution of 4 MUm to 4.5 MUm and transverse resolution of 10 MUm to 15 MUm.
      RESULTS: Among eyes with unexplained vision loss, visual acuity ranged from 20/20
      to 20/80 and central scotoma was noted in all eyes by microperimetry or Amsler
      grid. Fourier-domain optical coherence tomography showed abnormality in the
      foveal photoreceptor (PR) layer in six eyes from four subjects (67%). These
      abnormalities include focal loss of the PR layer with microcystoid changes in the
      macula (n = 2), focal discontinuity of the PR layer (n = 3), and focal elevation
      and blurring of the PR layer associated with a mild epiretinal membrane (n = 1).
      Among age-matched control eyes, no foveal PR abnormality was seen. CONCLUSION:
      Fourier-domain optical coherence tomography detected subtle changes in the foveal
      PR layer in some eyes with vision loss and central scotoma unexplained with
      routine clinical diagnostic tests.

PMID- 22880138
TI  - Administration of triclabendazole is safe and effective in controlling
      fascioliasis in an endemic community of the Bolivian Altiplano.
AB  - BACKGROUND: The Bolivian northern Altiplano is characterized by a high prevalence
      of Fasciola hepatica infection. In order to assess the feasibility, safety and
      efficacy of large-scale administration of triclabendazole as an appropriate
      public health measure to control morbidity associated with fascioliasis, a pilot
      intervention was implemented in 2008. MATERIALS AND METHODS: Schoolchildren from
      an endemic community were screened for fascioliasis and treated with a single
      administration of triclabendazole (10 mg/kg). Interviews to assess the occurrence
      of adverse events were conducted on treatment day, one week later, and one month
      after treatment. Further parasitological screenings were performed three months
      after treatment and again two months later (following a further treatment) in
      order to evaluate the efficacy of the intervention. RESULTS: Ninety infected
      children were administered triclabendazole. Adverse events were infrequent and
      mild. No serious adverse events were reported. Observed cure rates were 77.8%
      after one treatment and 97.8% after two treatments, while egg reduction rates
      ranged between 74% and 90.3% after one treatment, and between 84.2% and 99.9%
      after two treatments. The proportion of high-intensity infections (>= 400 epg)
      decreased from 7.8% to 1.1% after one treatment and to 0% after two treatments.
      CONCLUSION: Administration of triclabendazole is a feasible, safe and efficacious
      public health intervention in an endemic community in the Bolivian Altiplano,
      suggesting that preventive chemotherapy can be applied to control of
      fascioliasis. Further investigations are needed to define the most appropriate
      frequency of treatment.

PMID- 22880139
TI  - Moving from rabies research to rabies control: lessons from India.
AB  - BACKGROUND: Despite the availability of effective interventions and public
      recognition of the severity of the problem, rabies continues to suffer neglect by
      programme planners in India and other low and middle income countries. We
      investigate whether this state of 'policy impasse' is due to, at least in part,
      the research community not catering to the information needs of the policy
      makers.  METHODS #ENTITYSTARTX00026; FINDINGS: Our objective was to review the
      research output on rabies from India and examine its alignment with national
      policy priorities. A systematic literature review of all rabies research articles
      published from India between 2001 and 2011 was conducted. The distribution of
      conducted research was compared to the findings of an earlier research
      prioritization exercise. It was found that a total of 93 research articles were
      published from India since 2001, out of which 61% consisted of laboratory based
      studies focussing on rabies virus. Animals were the least studied group,
      comprising only 8% of the research output. One third of the articles were
      published in three journals focussing on vaccines and infectious disease
      epidemiology and the top 4 institutions (2 each from the animal and human health
      sectors) collectively produced 49% of the national research output. Biomedical
      research related to development of new interventions dominated the total output
      as opposed to the identified priority domains of socio-politic-economic research,
      basic epidemiological research and research to improve existing interventions.
      CONCLUSION: The paper highlights the gaps between rabies research and policy
      needs, and makes the case for developing a strategic research agenda that
      focusses on rabies control as an expected outcome.

PMID- 22880140
TI  - Refining the global spatial limits of dengue virus transmission by evidence-based
      consensus.
AB  - BACKGROUND: Dengue is a growing problem both in its geographical spread and in
      its intensity, and yet current global distribution remains highly uncertain.
      Challenges in diagnosis and diagnostic methods as well as highly variable
      national health systems mean no single data source can reliably estimate the
      distribution of this disease. As such, there is a lack of agreement on national
      dengue status among international health organisations. Here we bring together
      all available information on dengue occurrence using a novel approach to produce
      an evidence consensus map of the disease range that highlights nations with an
      uncertain dengue status. METHODS/PRINCIPAL FINDINGS: A baseline methodology was
      used to assess a range of evidence for each country. In regions where dengue
      status was uncertain, additional evidence types were included to either clarify
      dengue status or confirm that it is unknown at this time. An algorithm was
      developed that assesses evidence quality and consistency, giving each country an
      evidence consensus score. Using this approach, we were able to generate a
      contemporary global map of national-level dengue status that assigns a relative
      measure of certainty and identifies gaps in the available evidence. CONCLUSION:
      The map produced here provides a list of 128 countries for which there is good
      evidence of dengue occurrence, including 36 countries that have previously been
      classified as dengue-free by the World Health Organization and/or the US Centers
      for Disease Control. It also identifies disease surveillance needs, which we list
      in full. The disease extents and limits determined here using evidence consensus,
      marks the beginning of a five-year study to advance the mapping of dengue virus
      transmission and disease risk. Completion of this first step has allowed us to
      produce a preliminary estimate of population at risk with an upper bound of 3.97
      billion people. This figure will be refined in future work.

PMID- 22880141
TI  - Amoebae as potential environmental hosts for Mycobacterium ulcerans and other
      mycobacteria, but doubtful actors in Buruli ulcer epidemiology.
AB  - BACKGROUND: The reservoir and mode of transmission of Mycobacterium ulcerans, the
      causative agent of Buruli ulcer, remain unknown. Ecological, genetic and
      epidemiological information nonetheless suggests that M. ulcerans may reside in
      aquatic protozoa. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally infected
      Acanthamoeba polyphaga with M. ulcerans and found that the bacilli were
      phagocytised, not digested and remained viable for the duration of the
      experiment. Furthermore, we collected 13 water, 90 biofilm and 45 detritus
      samples in both Buruli ulcer endemic and non-endemic communities in Ghana, from
      which we cultivated amoeboid protozoa and mycobacteria. M. ulcerans was not
      isolated, but other mycobacteria were as frequently isolated from intracellular
      as from extracellular sources, suggesting that they commonly infect amoebae in
      nature. We screened the samples as well as the amoeba cultures for the M.
      ulcerans markers IS2404, IS2606 and KR-B. IS2404 was detected in 2% of the
      environmental samples and in 4% of the amoeba cultures. The IS2404 positive
      amoeba cultures included up to 5 different protozoan species, and originated both
      from Buruli ulcer endemic and non-endemic communities. CONCLUSIONS/SIGNIFICANCE:
      This is the first report of experimental infection of amoebae with M. ulcerans
      and of the detection of the marker IS2404 in amoeba cultures isolated from the
      environment. We conclude that amoeba are potential natural hosts for M. ulcerans,
      yet remain sceptical about their implication in the transmission of M. ulcerans
      to humans and their importance in the epidemiology of Buruli ulcer.

PMID- 22880142
TI  - Heterogeneity of environments associated with transmission of visceral
      leishmaniasis in South-Eastern France and implication for control strategies.
AB  - BACKGROUND: Visceral leishmaniasis due to Leishmania infantum is currently
      spreading into new foci across Europe. Leishmania infantum transmission in the
      Old World was reported to be strongly associated with a few specific
      environments. Environmental changes due to global warming or human activity were
      therefore incriminated in the spread of the disease. However, comprehensive
      studies were lacking to reliably identify all the environments at risk and
      thereby optimize monitoring and control strategy. METHODOLOGY/FINDINGS: We
      exhaustively collected 328 cases of autochthonous visceral leishmaniasis from
      1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31
      yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009
      mostly because Leishmania/HIV coinfection were less frequent. No spread of human
      visceral leishmaniasis was observed in the studied region. Two major foci were
      identified, associated with opposite environments: whereas one involved semi
      rural hillside environments partly made of mixed forests, the other involved
      urban and peri-urban areas in and around the region main town, Marseille. The two
      neighboring foci were related to differing environments despite similar vectors
      (P. perniciosus), canine reservoir, parasite (L. infantum zymodeme MON-1), and
      human host. CONCLUSIONS/SIGNIFICANCE: This unprecedented collection of cases
      highlighted the occurrence of protracted urban transmission of L. infantum in
      France, a worrisome finding as the disease is currently spreading in other areas
      around the Mediterranean. These results complete previous studies about more
      widespread canine leishmaniasis or human asymptomatic carriage. This first
      application of systematic geostatistical methods to European human visceral
      leishmaniasis demonstrated an unsuspected heterogeneity of environments
      associated with the transmission of the disease. These findings modify the
      current view of leishmaniasis epidemiology. They notably stress the need for
      locally defined control strategies and extensive monitoring including in urban
      environments.

PMID- 22880143
TI  - An analytical method for assessing stage-specific drug activity in Plasmodium
      vivax malaria: implications for ex vivo drug susceptibility testing.
AB  - The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has
      created an urgent need for an improved understanding of the mechanisms of drug
      resistance in these parasites, the development of robust tools for defining the
      spread of resistance, and the discovery of new antimalarial agents. The ex vivo
      Schizont Maturation Test (SMT), originally developed for the study of P.
      falciparum, has been modified for P. vivax. We retrospectively analysed the
      results from 760 parasite isolates assessed by the modified SMT to investigate
      the relationship between parasite growth dynamics and parasite susceptibility to
      antimalarial drugs. Previous observations of the stage-specific activity of CQ
      against P. vivax were confirmed, and shown to have profound consequences for
      interpretation of the assay. Using a nonlinear model we show increased duration
      of the assay and a higher proportion of ring stages in the initial blood sample
      were associated with decreased effective concentration (EC(50)) values of CQ, and
      identify a threshold where these associations no longer hold. Thus, starting
      composition of parasites in the SMT and duration of the assay can have a profound
      effect on the calculated EC(50) for CQ. Our findings indicate that EC(50) values
      from assays with a duration less than 34 hours do not truly reflect the
      sensitivity of the parasite to CQ, nor an assay where the proportion of ring
      stage parasites at the start of the assay does not exceed 66%. Application of
      this threshold modelling approach suggests that similar issues may occur for
      susceptibility testing of amodiaquine and mefloquine. The statistical methodology
      which has been developed also provides a novel means of detecting stage-specific
      drug activity for new antimalarials.

PMID- 22880144
TI  - Spectral-domain optical coherence tomography in healed ocular toxoplasmosis.

PMID- 22880145
TI  - Three-dimensional spectral-domain optical coherence tomography of melanocytoma of
      the optic nerve head.

PMID- 22880147
TI  - Srf: A key factor controlling skeletal muscle hypertrophy by enhancing the
      recruitment of muscle stem cells.
AB  - Adult skeletal muscles adapt their fiber size to workload. We show that serum
      response factor (Srf) is required for satellite cell-mediated hypertrophic muscle
      growth. Deletion of Srf from myofibers, and not satellite cells, blunts overload
      induced hypertrophy, and impairs satellite cell proliferation and recruitment to
      pre-existing fibers. We reveal a gene network in which Srf within myofibers
      modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and
      therefore exerts a paracrine control of satellite cell functions. In Srf-deleted
      muscles, in vivo overexpression of interleukin-6 is sufficient to restore
      satellite cell proliferation, but not satellite cell fusion and overall growth.
      In contrast, cyclooxygenase-2/interleukin-4 overexpression rescues satellite cell
      recruitment and muscle growth without affecting satellite cell proliferation,
      identifying altered fusion as the limiting cellular event. These findings unravel
      a role for Srf in the translation of mechanical cues applied to myofibers into
      paracrine signals, which in turn will modulate satellite cell functions and
      support muscle growth.

PMID- 22880148
TI  - Parvin-ILK: An intimate relationship.
AB  - Integrin-linked kinase (ILK), PINCH and Parvin proteins form the IPP-complex that
      has been established as a core component of the integrin-actin link. Our recent
      genetic studies on Drosophila parvin, reveal that loss of function mutant defects
      phenocopy those observed upon loss of ILK or PINCH in the muscle and the wing,
      strengthening the notion that these proteins function together in the organism.
      Our work identified that ILK is necessary and sufficient for parvin subcellular
      localization, corroborating previous data indicating a direct association between
      these two proteins. Further genetic epistasis analysis of the IPP-complex
      assembly at integrin adhesion sites reveals that depending on the cell context
      each component is required differently. At the muscle attachment sites of the
      embryo, ILK is placed upstream in the hierarchy of genetic interactions required
      for the IPP-complex assembly. By contrast, in the wing epithelium the three
      proteins are mutually interdependent. Finally, we uncovered a novel property for
      the CH1-domain of parvin: its recruitment at the integrin-containing junctions in
      an ILK-dependent manner. Apparently, this ability of the CH1-domain is controlled
      by the inter-CH linker region. Thus, an intramolecular interaction within parvin
      could serve as a putative regulatory mechanism controlling the ILK-Parvin
      interaction.

PMID- 22880146
TI  - The actin cytoskeleton as a sensor and mediator of apoptosis.
AB  - Apoptosis is an important biological process required for the removal of unwanted
      or damaged cells. Mounting evidence implicates the actin cytoskeleton as both a
      sensor and mediator of apoptosis. Studies also suggest that actin binding
      proteins (ABPs) significantly contribute to apoptosis and that actin dynamics
      play a key role in regulating apoptosis signaling. Changes in the organization of
      the actin cytoskeleton has been attributed to the process of malignant
      transformation and it is hypothesized that remodeling of the actin cytoskeleton
      may enable tumor cells to evade normal apoptotic signaling. This review aims to
      illuminate the role of the actin cytoskeleton in apoptosis by systematically
      analyzing how actin and ABPs regulate different apoptosis pathways and to also
      highlight the potential for developing novel compounds that target tumor-specific
      actin filaments.

PMID- 22880149
TI  - TSPAN7: A new player in excitatory synapse maturation and function.
AB  - Tetraspanins regulate the signaling, trafficking and biosynthetic processing of
      associated proteins, and may link the extracellular domain of alpha-chain
      integrins with intracellular signaling molecules, including PI4K and PKC, both of
      which regulate cytoskeletal architecture. We showed that TSPAN7, a member of
      tetraspannin-family, promotes filopodia and dendritic spine formation in cultured
      hippocampal neurons, and is required for spine stability and normal synaptic
      transmission. TSPAN7 directly interacts with the PDZ domain of protein
      interacting with C kinase 1 (PICK1), and associates with AMPAR subunit GluA2 and
      beta1-integrin. TSPAN7 regulates PICK1 and GluA2/3 association, and AMPA receptor
      trafficking. These findings identify TSPAN7 as a key player in the morphological
      and functional maturation of glutamatergic synapses.

PMID- 22880150
TI  - Shaping muscle bioarchitecture for the fin to limb transition.
AB  - Our recent paper examined how pelvic fins and their musculature form
      developmentally and how these mechanisms have evolved within the vertebrate
      lineage, a process fundamental to the tetrapod transition. The transition from
      the water onto the land is among one of the most well studied steps in the
      evolutionary history of vertebrates, yet the genetic basis of this evolutionary
      transition is little studied and ill-defined. The advent of these terrestrial
      species resulted in a shift in locomotor strategies from the rhythmic undulating
      muscles of the fish body to a reliance upon powerful weight bearing muscles of
      the limbs to generate movement. We demonstrated that the pelvic fin muscles of
      bony fish are generated by a mechanism that has features of both of limb/fin
      muscle formation in tetrapods and primitive cartilaginous fish. We hypothesize
      that the adoption of the fully derived mode of hindlimb muscle formation, was a
      further modification of the mode of development deployed to generate pelvic fin
      muscles, a shift in overall muscle bioarchitecture we believe was critical to the
      success of the tetrapod transition.

PMID- 22880151
TI  - The BAF60c-MyoD complex poises chromatin for rapid transcription.
AB  - Chromatin remodeling by the SWI/SNF complex is required to activate the
      transcription of myogenic-specific genes. Our work addressed the details of how
      SWI/SNF is recruited to myogenic regulatory regions in response to
      differentiation signals. Surprisingly, the muscle determination factor MyoD and
      the SWI/SNF subunit BAF60c form a complex on the regulatory elements of MyoD
      targeted genes in myogenic precursor cells. This Brg1-devoid MyoD-BAF60c complex
      flags the chromatin of myogenic-differentiation genes before transcription is
      activated. On differentiation, BAF60c phosphorylation on a conserved threonine by
      p38 alpha kinase promotes the incorporation of MyoD-BAF60c into a Brg1-based
      SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD
      target genes. Downregulation of BAF60c expression prevents MyoD access to the
      chromatin and the proper loading of an active myogenic transcriptosome preventing
      the expression of hundreds of myogenic genes. Our data support an unprecedented
      two-step model by which (1) pre-assembled BAF60c-MyoD complex poises the
      chromatin of myogenic genes for rapid transcription; (2) chromatin-bound BAF60c
      "senses" the myogenic differentiation cues and recruits an active SWI/SNF complex
      to remodel the chromatin allowing transcriptional activation.

PMID- 22880152
TI  - Differences in obesity rates between people with and without disabilities and the
      association of disability and obesity: a nationwide population study in South
      Korea.
AB  - OBJECTIVES: The objective of this study was to identify the differences in
      obesity rates among people with and without disabilities, and evaluate the
      relationship between obesity rates and the existence of disabilities or
      characteristics of disabilities. METHODS: Mass screening data from 2008 from the
      National Disability Registry and National Health Insurance (NHI) are used. For
      analysis, we classified physical disability into three subtypes: upper limb
      disability, lower limb disability, and spinal cord injury. For a control group,
      we extracted people without disabilities by each subtype. To adjust for the
      participation rate in the NHI mass screening, we calculated and adopted the
      weight stratified by sex, age, and grade of disability. Differences in obesity
      rates between people with and without disabilities were examined by a chi-squared
      test. In addition, the effect of the existence of disabilities and grade of
      disabilities on obesity was examined by multiple logistic regression analysis.
      RESULTS: People with disabilities were found to have a higher obesity rate than
      those without disabilities. The obesity rates were 35.2% and 35.0% (people with
      disabilities vs. without disabilities) in the upper limb disability, 44.5% and
      34.8% in the lower limb disability, 43.4% and 34.6% in the spinal cord injury.
      The odds for existence of physical disability and grade of disability are higher
      than the non-disabilities. CONCLUSIONS: These results show that people with
      physical disability have a higher vulnerability to obesity.

PMID- 22880153
TI  - Zolpidem use and risk of fracture in elderly insomnia patients.
AB  - OBJECTIVES: To evaluate the risk of fractures related with zolpidem in elderly
      insomnia patients. METHODS: Health claims data on the entire South Korean elderly
      population from January 2005 to June 2006 were extracted from the Health
      Insurance Review and Assessment Service database. We applied a case-crossover
      design. Cases were defined as insomnia patients who had a fracture diagnosis. We
      set the hazard period of 1 day length prior to the fracture date and four control
      periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date.
      Time independent confounding factors such as age, gender, lifestyle, cognitive
      function level, mobility, socioeconomic status, residential environment, and
      comorbidity could be controlled using the case-crossover design. Time dependent
      confounding factors, especially co-medication of patients during the study
      period, were adjusted by conditional logistic regression analysis. The odds
      ratios and their 95% confidence intervals (CIs) were estimated for the risk of
      fracture related to zolpidem. RESULTS: One thousand five hundred and eight cases
      of fracture were detected in insomnia patients during the study period. In our
      data, the use of zolpidem increased the risk of fracture significantly (adjusted
      odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between
      benzodiazepine hypnotics and the risk of fracture was not statistically
      significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not
      statistically significant in stratified analysis with each benzodiazepine generic
      subgroup. CONCLUSIONS: Zolpidem could increase the risk of fracture in elderly
      insomnia patients. Therefore zolpidem should be prescribed carefully and the
      elderly should be provided with sufficient patient education.

PMID- 22880154
TI  - Relationship between body mass index and early menarche of adolescent girls in
      Seoul.
AB  - OBJECTIVES: The object of this study was to determine the relationship between
      body mass index (BMI) and early menarche in adolescent girls in Seoul. METHODS: A
      retrospective study was conducted with 144 middle school students in Seoul who
      provided informed consent. We measured their body composition, and used the
      questionnaire survey method for data collection from November to December 2008.
      Past elemental body composition data were collected from elementary school health
      records of first year of middle school. RESULTS: The early menarcheal group was
      taller and heavier than the late menarcheal group (p<0.05 from 8-12 years old).
      The body fat percentage (%), BMI were higher in the early menarcheal girls than
      the late-menarcheal girls (p<0.05, age at 13). In the result of multiple logistic
      regression, the BMI at the age of 8 and 9 was associated with early menarche
      after adjusting for birth weight, breast feeding and age at menarche of the
      mother (BMI at the age of 8: p for trend=0.01, BMI at the age of 9: p for
      trend=0.04). An increase in BMI from 7 to 8 year was associated with early
      menarche after adjusting for birth weight, breast feeding, age at menarche of the
      mother (p for trend=0.048). CONCLUSIONS: The BMI at the age of 8 and 9 was
      associated with the early menarche of girls and increase in BMI from 7 to 8 year
      was associated with the early menarche of girls. These results suggest that BMI
      and increase in BMI before menarche cause early menarche. Although this study
      does not represent all Korean adolescent girls, it is one of the few studies that
      have investigated the temporal relationship between BMI and early menarche.

PMID- 22880155
TI  - Nail DNA and possible biomarkers: a pilot study.
AB  - OBJECTIVES: Nail has been a substitute DNA source for genotyping. To investigate
      the integrity and consistency of nail DNA amplification for biomarker study, nail
      clippings from 12 subjects were collected at monthly intervals. The possibility
      of longer amplification and existence of GAPDH RNA/protein, were also
      investigated with three nail samples. METHODS: Three primer sets were designed
      for quantitative amplification of nuclear and mitochondrial genes and analysis of
      their consistency. The mean threshold cycles in amplification of the target genes
      were compared to test the consistency of polymerase chain reaction (PCR)
      performance among individual factors including age groups, sex, family, the nail
      source, and by the size of the amplification segments. RESULTS: The amplification
      of the target genes from nail DNA showed similar integrity and consistency
      between the nail sources, and among the serial collections. However, nail DNA
      from those in their forties showed earlier threshold cycles in amplification than
      those in their teens or seventies. Mitochondrial DNA (mtDNA) showed better DNA
      integrity and consistency in amplification of all three targets than did nuclear
      DNA (nucDNA). Over 9 kb of mtDNA was successfully amplified, and nested
      quantitative PCR showed reliable copy numbers (%) between the two loci. Reverse
      transcription PCR for mRNA and immunoblotting for GAPDH protein successfully
      reflected their corresponding amounts. Regarding the existence of RNA and protein
      in nails, more effective extraction and detection methods need to be set up to
      validate the feasibility in biomarker study. CONCLUSIONS: Nail DNA might be a
      feasible intra-individual monitoring biomarker. Considering integrity and
      consistency in target amplification, mtDNA would be a better target for biomarker
      research than nucDNA.

PMID- 22880156
TI  - Psychological, social, and environmental factors associated with utilization of
      senior centers among older adults in Korea.
AB  - OBJECTIVES: The purpose of the study was to examine the relationships among the
      psychological, social, and environmental factors influencing the utilization of
      senior centers among older adults in Korea. METHODS: A questionnaire survey was
      administered to two types of older adults who lived in Seoul, Korea: 262 older
      adults who used senior centers (3 places) and 156 older adults who did not use
      senior centers. RESULTS: Our results showed clearly that the utilization of the
      senior centers in Korea is affected by higher self-efficacy (odds ratio [OR],
      6.08; 95% confidence interval [CI], 3.31 to 12.32), higher perceived benefits
      (OR, 1.71; 95% CI, 1.16 to 4.36), lower perceived barriers (OR, 6.43; 95% CI,
      3.07 to 11.45), higher family support (OR, 4.21; 95% CI, 2.02 to 8.77), and
      higher support from friends (OR, 4.08; 95% CI, 2.38 to 7.81). The results also
      showed that participants whose total travel time was 15 to 29 minutes (OR, 2.84;
      95% CI, 1.21 to 3.64) or less than 14 minutes (OR, 4.68; 95% CI, 3.41 to 8.41)
      were more likely to use a senior center than those who had to travel more than 30
      minutes. CONCLUSIONS: This study showed that the utilization of senior centers in
      Korea is affected by psychological, social, and environmental factors,
      specifically by self-efficacy, perceived benefits, perceived barriers, social
      support, convenience of transportation, and total travel time to the senior
      centers. The effects of longer-term utilization of the senior centers by non
      users on health-related outcomes in a large population warrant attention.

PMID- 22880157
TI  - Quantitative analysis of cancer-associated gene methylation connected to risk
      factors in Korean colorectal cancer patients.
AB  - OBJECTIVES: The purpose of this paper was to elucidate the potential methylation
      levels of adjacent normal and cancer tissues by comparing them with normal
      colorectal tissues, and to describe the correlations between the methylation and
      clinical parameters in Korean colorectal cancer (CRC) patients. METHODS:
      Hypermethylation profiles of nine genes (RASSF1, APC, p16(INK4a), Twist1, E
      cadherin, TIMP3, Smad4, COX2, and ABCB1) were examined with 100 sets of cancer
      tissues and 14 normal colorectal tissues. We determined the hypermethylation at a
      given level by a percent of methylation ratio value of 10 using quantitative
      methylation real-time polymerase chain reaction. RESULTS: Nine genes'
      hypermethylation levels in Korean CRC patient tissues were increased more higher
      than normal colorectal tissues. However, the amounts of p16(INK4a) and E-cadherin
      gene hypermethylation in normal and CRC tissues were not significantly different
      nor did TIMP3 gene hypermethylation in adjacent normal and cancer tissues differ
      significantly. The hypermethylation of TIMP3, E-cadherin, ABCB1, and COX2 genes
      among other genes were abundantly found in normal colorectal tissues. The
      hypermethylation of nine genes' methylation in cancer tissues was not
      significantly associated with any clinical parameters. In Cohen's kappa test, it
      was moderately observed that RASSF1 was related with E-cadherin, and Smad4 with
      ABCB1 and COX2. CONCLUSIONS: This study provides evidence for different
      hypermethylation patterns of cancer-associated genes in normal and CRC tissues,
      which may serve as useful information on CRC cancer progression.

PMID- 22880158
TI  - Selecting the best prediction model for readmission.
AB  - OBJECTIVES: This study aims to determine the risk factors predicting
      rehospitalization by comparing three models and selecting the most successful
      model. METHODS: In order to predict the risk of rehospitalization within 28 days
      after discharge, 11 951 inpatients were recruited into this study between January
      and December 2009. Predictive models were constructed with three methods,
      logistic regression analysis, a decision tree, and a neural network, and the
      models were compared and evaluated in light of their misclassification rate, root
      asymptotic standard error, lift chart, and receiver operating characteristic
      curve. RESULTS: The decision tree was selected as the final model. The risk of
      rehospitalization was higher when the length of stay (LOS) was less than 2 days,
      route of admission was through the out-patient department (OPD), medical
      department was in internal medicine, 10th revision of the International
      Classification of Diseases code was neoplasm, LOS was relatively shorter, and the
      frequency of OPD visit was greater. CONCLUSIONS: When a patient is to be
      discharged within 2 days, the appropriateness of discharge should be considered,
      with special concern of undiscovered complications and co-morbidities. In
      particular, if the patient is admitted through the OPD, any suspected disease
      should be appropriately examined and prompt outcomes of tests should be secured.
      Moreover, for patients of internal medicine practitioners, co-morbidity and
      complications caused by chronic illness should be given greater attention.

PMID- 22880159
TI  - Health impact assessment of free immunization program in Jinju City, Korea.
AB  - OBJECTIVES: This study was conducted to assess the potential health impacts and
      improve the quality of the free immunization program in Jinju City by maximizing
      the predicted positive health gains and minimizing the negative health risks.
      METHODS: A steering committee was established in September 2010 to carry out the
      health impact assessment (HIA) and began the screening and scoping stages. In the
      appraisal stage, analysis of secondary data, a literature review, case studies,
      geographic information systems analysis, a questionnaire, and expert
      consultations were used. The results of the data collection and analyses were
      discussed during a workshop, after which recommendations were finalized in a
      written report. RESULTS: Increased access to immunization, comprehensive services
      provided by physicians, the strengthened role of the public health center in
      increasing immunization rates and services, and the ripple effect to other
      neighboring communities were identified as potential positive impacts. On the
      other hand, the program might be inaccessible to rural regions with no private
      clinics where there are more at-risk children, vaccine management and quality
      control at the clinics may be poor, and vaccines may be misused. Recommendations
      to maximize health gains and minimize risks were separately developed for the
      public health center and private clinics. CONCLUSIONS: The HIA provided an
      opportunity for stakeholders to comprehensively overview the potential positive
      and negative impacts of the program before it was implemented. An HIA is a
      powerful tool that should be used when developing and implementing diverse health
      related policies and programs in the community.

PMID- 22880160
TI  - A direct borohydride fuel cell with a polymer fiber membrane and non-noble metal
      catalysts.
AB  - Polymer electrolyte membranes (PEM) and Pt-based catalysts are two crucial
      components which determine the properties and price of fuel cells. Even though,
      PEM faces problem of fuel crossover in liquid fuel cells such as direct methanol
      fuel cell (DMFC) and direct borohydride fuel cell (DBFC), which lowers power
      output greatly. Here, we report a DBFC in which a polymer fiber membrane (PFM)
      was used, and metal oxides, such as LaNiO3 and MnO2, were used as cathode
      catalysts, meanwhile CoO was used as anode catalyst. Peak power density of 663
      mW.cm-2 has been achieved at 65 degrees C, which increases by a factor of 1.7-3.7
      compared with classic DBFCs. This fuel cell structure can also be extended to
      other liquid fuel cells, such as DMFC.

PMID- 22880161
TI  - The biological impacts of the Fukushima nuclear accident on the pale grass blue
      butterfly.
AB  - The collapse of the Fukushima Dai-ichi Nuclear Power Plant caused a massive
      release of radioactive materials to the environment. A prompt and reliable system
      for evaluating the biological impacts of this accident on animals has not been
      available. Here we show that the accident caused physiological and genetic damage
      to the pale grass blue Zizeeria maha, a common lycaenid butterfly in Japan. We
      collected the first-voltine adults in the Fukushima area in May 2011, some of
      which showed relatively mild abnormalities. The F1 offspring from the first
      voltine females showed more severe abnormalities, which were inherited by the F2
      generation. Adult butterflies collected in September 2011 showed more severe
      abnormalities than those collected in May. Similar abnormalities were
      experimentally reproduced in individuals from a non-contaminated area by external
      and internal low-dose exposures. We conclude that artificial radionuclides from
      the Fukushima Nuclear Power Plant caused physiological and genetic damage to this
      species.

PMID- 22880162
TI  - Development of Chlamydial Type III Secretion System Inhibitors for Suppression of
      Acute and Chronic Forms of Chlamydial Infection.
AB  - The Type III secretion system (T3SS) is currently considered to be one of the
      main pathogenicity factors in Gram-negative bacteria, which exhibit different
      types of parasitizing activity. The presence of this structure is essential for
      the development of an acute infection; the chronicity of the infection is
      fundamentally dependent upon its functioning. In this regard, T3TS is one of the
      most promising targets for the development of broad-spectrum antimicrobial drugs
      that do not develop resistance and are efficacious for the acute and chronic
      forms of infection. The mechanism of action in drug development is based on the
      specific inhibition of T3SS, which should interrupt the infectious process,
      thereby enabling the immune system to eliminate the pathogen. As a result of
      pilot screening using specific cellular and bacterial tests, followed by chemical
      optimization and detailed characterization of the biological activity, a new
      class of chlamydial T3SS inhibitors was obtained. The selected compounds have
      obvious advantages over the currently available inhibitors of T3SS pathogens
      thanks to the high inhibitory activity of these compounds with minimal damaging
      effects on eukaryotic cells. Preclinical trials of the selected inhibitors are
      currently under way.

PMID- 22880163
TI  - Recombinant Human Cyclophilin A in vitro Inhibits the Formation of Fibrin Clot.
AB  - The chemotactic properties of cyclophilin A are well-known. There exists however
      a poor level of understanding regarding the hemostatic effects of this protein.
      Herein it is shown that recombinant human cyclophilin A (rhSyA), in contrast to
      the granulocyte colony-stimulating factor, is capable of inhibitingin vitrothe
      formation of a fibrin clot, thereby violating the spatial dynamics of clot
      growth; this effect is transient and dose-independent. Furthermore, the
      hypothesis that the conformational changes in the thrombin-rhCyA complex may
      mediate the anticoagulant effect of rhCyA on the autowave processes of blood
      clotting is postulated.

PMID- 22880164
TI  - Aortic valve sparing operations: a review.
AB  - Aortic valve sparing operations were developed to preserve the native aortic
      valve during surgery for aortic root aneurysm as well as surgery for ascending
      aortic aneurysms with associated aortic insufficiency. There are basically two
      types of aortic valve sparing oprations: remodeling of the aortic root and
      reimplantation of the aortic valve. These operations have been performed for over
      two decades and the clinical outcomes have been excellent in experienced hands.
      Although remodeling of the aortic root is physiologically superior to
      reimplantation of the aortic valve, long-term follow-up suggests that the latter
      is associated with lower risk of developing aortic insufficiency. Failure of
      remodeling of the aortic root is often due to dilatation of the aortic annulus.
      Thus, this type of aortic valve sparing should be reserved for older patients
      with ascending aortic aneurysm and normal aortic annulus whereas reimplantation
      of the aortic valve is more appropriate for young patients with inherited
      disorders that cause aortic root aneurysms. This article summarizes the published
      experience with these two operations. They are no longer experimental procedures
      and should be part of the surgical armamentarium to treat patients with aortic
      root aneurysm and ascending aortic aneurysms with associated aortic
      insufficiency.

PMID- 22880165
TI  - Tetralogy of fallot: a surgical perspective.
AB  - Tetralogy of Fallot (TOF) is an index lesion for all paediatric and congenital
      heart surgeons. In designing an appropriate operation for children with TOF, the
      predicted postoperative physiology must be taken into account, both for the short
      and long term. A favourable balance between pulmonary stenosis (PS) and pulmonary
      insufficiency (PI) may be critical for preservation of biventricular function. A
      unified repair strategy to limit both residual PS and PI is presented, along with
      supportive experimental evidence. A strategy for dealing with coronary anomalies
      and some comments regarding best timing of operation are also included.

PMID- 22880166
TI  - Comparative analysis of thoracotomy and sternotomy approaches in cardiac
      reoperation.
AB  - BACKGROUND: Reoperation of cardiac surgery via median sternotomy can be
      associated with significant complications. Thoracotomy is expected to reduce the
      risk of reoperation and to enhance the surgical outcomes. We retrospectively
      analyzed two operative approaches (thoracotomy vs. sternotomy) in cardiac
      reoperation. MATERIALS AND METHODS: From September 2007 to December 2010, 35
      patients who required reoperation of the mitral valvular disease following
      previous median sternotomy were included. Average age of patients was 45.8+/-15.4
      years (range, 14 to 76 years) and male-to-female was 23:12. Interval period
      between primary operation and reoperation was 135.8+/-105.6 months (range, 3.3 to
      384.9 months). RESULTS: Comparative analysis was done dividing the patient group
      into two groups that are thoracotomy group (22 patients) and sternotomy group (13
      patients). Thoracotomy group was significantly lower in operative time (415.2+/
      90.3 vs. 497.5+/-148.0, p<0.05), bleeding control time (108.0+/-29.5 vs. 146.4+/
      66.8, p<0.05) and chest tube drainage (287.5+/-211.5 mL vs. 557.3+/-365.5 mL,
      p<0.05) compared to sternotomy group. CONCLUSION: The thoracotomy approach is
      superior to sternotomy in some variables, and it is considered as a valid
      alternative to repeat median sternotomy in patients who underwent a previous
      median sternotomy.

PMID- 22880167
TI  - Factors affecting the postoperative mortality in the ruptured abdominal aortic
      aneurysm.
AB  - BACKGROUND: Although patients with a ruptured abdominal aortic aneurysm (RAAA)
      often reach the hospital alive, the perioperative mortality is still very high.
      We retrospectively reviewed thirty patients who underwent repair of RAAA to
      identify the factors affecting postoperative mortality in a single hospital.
      MATERIALS AND METHODS: Between September 2007 and May 2011, thirty patients with
      RAAA underwent emergent surgery (n=27) or endovascular aneurysm repair (n=3).
      Their medical records were retrospectively reviewed regarding three categories:
      1) preoperative patient status: age, gender, vital signs, serum creatinine, blood
      urea nitrogen, hematocrit, and hemoglobin level: 2) aneurysmal status: size,
      type, and rupture status; and 3) operative factors: interval time to operating
      room, operative duration, and amount of perioperative transfusion. RESULTS: The
      30-day postoperative mortality rate was 13.3% (4/30); later mortality was 3.3%
      (1/30). On multivariate analysis, the initial diastolic blood pressure (BP),
      interval time to operating room and amount of preoperative packed cell
      transfusion were statistically significantly linked with postoperative mortality
      (p<0.05). CONCLUSION: In this study, preoperative diastolic BP, preoperative
      packed cell transfusion amount and interval time between arrival and entry to
      operating room were significantly associated with postoperative mortality. It is
      important to prevent hemorrhage as quickly as possible.

PMID- 22880168
TI  - Prognosis in the patients with prolonged extracorporeal membrane oxygenation.
AB  - BACKGROUND: Prolonged usage of extracorporeal membrane oxygenation (ECMO) may
      induce multi-organ failure. This study is aimed to evaluate prognostic factors in
      the patients with ECMO. Also, the prognosis of ECMO with Kidney Injury Network
      Scoring system is studied. MATERIALS AND METHODS: From May 2005 to July 2011, 172
      cases of ECMO were performed. The cases of perioperative use of ECMO were
      excluded. Renal failure patient and younger than 15 years old one were also
      excluded. As a result, 26 cases were enrolled in this study. Male patients were
      15 (57.7%), and mean age was 56.57+/-17.03 years old. Demographic data, ECMO
      parameters, weaning from ECMO, and application of continuous renal replacement
      therapy are collected and Acute Kidney Injury Network (AKIN) scores were
      evaluated just before ECMO and day 1, day 2 during application of ECMO. RESULTS:
      Venoarterial ECMO was applied in 22 cases (84.6%). The reasons for applications
      of ECMO were cardiac origin in 21 (80.8%), acute respiratory distress syndrome in
      4, and septic shock in 1 case. Successful weaning from ECMO was achieved in 15
      cases (57.7%), and survival discharge rate was 9 cases (34.6%). Mean duration of
      application of ECMO was 111.39+/-54.06 hours. In univariate analysis, myocarditis
      was independent risk factors on weaning failure. Using the receiver operating
      characteristic curve, level of hemoglobin on 24 hours after ECMO, and base excess
      on 48 hours after ECMO were showed more than 0.7. AKIN score was not matched the
      prognosis of the patients with ECMO. CONCLUSION: In our study, the prognosis of
      the patients with myocarditis was poor. Hemoglobin level at first 24 hours, and
      degree of acidosis at 48 hours were useful methods in relating with prognosis of
      ECMO. AKIN scoring system was not related with the prognosis of the patients.
      Further study for prognosis and organ injury during application ECMO may be
      needed.

PMID- 22880170
TI  - Clinical Analysis for the Correlation of Intra-abdominal Organ Injury in the
      Patients with Rib Fracture.
AB  - BACKGROUND: Although it is rare for the fracture itself to become a life
      threatening injury in patients suffering from rib fracture, the lives of these
      patients are occasionally threatened by other associated injuries. Especially,
      early discovery of patients with rib fracture and intra-abdominal organ injury is
      extremely important to the prognosis. This study analyzed the link between rib
      fracture and intra-abdominal injury to achieve improved treatment. MATERIALS AND
      METHODS: Among trauma patients that had visited the hospital emergency room from
      January 2007 to December 2009, a retrospective study was conducted on 453
      patients suffering from rib fracture due to blunt trauma. Rib fracture was
      classified according to location (left, right, and bilateral), and according to
      level (upper rib fracture [1-2nd rib], middle rib fracture [3-8th rib], and lower
      rib fracture [9-12th rib]). The researched data was statistically compared and
      analyzed to investigate the correlation between the location, level, and number
      of rib fracture and intra-abdominal organ injury. RESULTS: Motor vehicle injury
      was found to be the most common mechanism of injury with 208 cases (46%).
      Associated injuries accompanied with rib fracture were generated in 276 cases
      (61%). Intra-abdominal organ injury was discovered in 97 cases (21%). Liver
      injury was the most common intra-abdominal injury associated with rib fracture
      with 39 cases (40%), followed by spleen injury, with 23 cases (23%). Intra
      abdominal injury according to level of rib fracture was presented as upper rib
      fracture in 11 cases (11%), middle rib fracture in 31 cases (32%), and lower rib
      fracture in 55 cases (57%), thus verifying that intra-abdominal injuries were
      commonly accompanied in lower rib fractures (p=0.03). In particular, significant
      increase of intra-abdominal injury was presented in fractures below the 8th rib
      (p=0.03). The number of intra-abdominal injuries requiring emergency operations
      was significantly higher in patients with more than 6 rib fractures (p=0.04).
      CONCLUSION: Intra-abdominal organ injury is more common in patients with lower
      rib fracture, especially fractures below the 8th rib. Intra-abdominal organ
      injuries generated in multiple rib fracture patients with more than 6 fractures
      significantly higher severity. These cases must be thoroughly inspected and
      carefully observed as there is possibility of emergency operation.

PMID- 22880169
TI  - Result of surgical resection for pulmonary metastasis from urothelial carcinoma.
AB  - BACKGROUND: Treatment of pulmonary metastasis from urothelial cell carcinoma has
      been mostly palliative chemotherapy and the role of pulmonary metastasectomy has
      not been investigated much. MATERIALS AND METHODS: This study is a retrospective
      interim review of pulmonary metastasectomy from urothelial carcinoma at single
      institution between 1998 and 2010. Overall 16 patients underwent pulmonary
      metastasectomies. RESULTS: There was no postoperative complication or hospital
      mortality. Mean hospital stay was 6 days. Overall and disease-free 5-year
      survival were 65.3% and 37.5%, respectively. CONCLUSION: In selected patients
      with pulmonary metastasis from urothelial carcinoma, surgical treatment is
      feasible and could contribute to long-term survival in selected patients.

PMID- 22880171
TI  - Redo-Coronary Artery Bypass due to Progression of the Celiac Axis Stenosis.
AB  - We report a redo coronary artery bypass grafting (CABG) in a 55-year-old man.
      Angina recurred 7 years after the initial surgery. Coronary angiography showed
      all patent grafts except a faint visualization of the in situ right
      gastroepiploic artery (RGEA) graft, which was anastomosed to the posterior
      descending coronary artery, associated with celiac axis stenosis. Redo-CABG was
      performed at postoperative 10 years because of aggravated angina and decreased
      perfusion of the inferior wall in the myocardial single photon emission computed
      tomography. The saphenous vein graft was interposed between the 2 in situ grafts
      used previously; the right internal thoracic artery and RGEA grafts. Angina was
      relieved and myocardial perfusion was improved.

PMID- 22880172
TI  - Cystic Mass on Right Atrium of Unusual Form of Chiari's Network: A Case Report.
AB  - Chiari's networks are present in 1.5% to 4% of the population. They are a
      congenital disease characterized by a remnant of the right valve of sinus venosus
      and rarely have clinical significance. Chiari's network, as the name implies, has
      network-like shape, but there are other forms of appearance. We have experienced
      a case of a 60-year-old woman who had a cystic mass on the right atrium. Surgical
      treatment was performed forthe mass removal and differential diagnosis of the
      mass. There was no evidence of other tumor, but Chiari's network. As cystic form
      of Chiari's network have not been reported before, it is the first report of
      cystic form of Chiari's network.

PMID- 22880173
TI  - Descending thoracic aorta to bilateral femoral artery bypass in a hostile
      abdomen.
AB  - Descending thoracic aorta to femoral artery bypass has been used as a remedial
      operation after aortic or axillofemoral graft failure or graft infection and
      other intra-abdominal pathologies not amenable to standard aortofemoral
      revascularization. It can avoid abdomen approach and has been known as a durable
      procedure with excellent long-term patency. We reported descending thoracic aorta
      to femoral artery bypass grafting for primary revascularization in a 55-year-old
      male with hostile abdominal conditions.

PMID- 22880174
TI  - Acute Postpneumonectomy Empyema with Bronchopleural Fistula Treated with Vacuum
      assisted Closure Device.
AB  - Postpneumonectomy empyema is a life-threatening complication, which is often
      related with a bronchopleural fistula. After surgical repair of fistula,
      sterilization of infected pleural cavity is important and usually carried out by
      long-term cyclic irrigation. We report a case in which vacuum-assisted closure
      device was successfully applied to sterilize the pleural cavity and obliterate
      bronchopleural fistula.

PMID- 22880175
TI  - An Endobronchial Inflammatory Myofibroblastic Tumor Treated by Modified Left One
      stoma-type Carinoplasty.
AB  - Endobronchial inflammatory myofibroblastic tumor is a rare primary lung disease.
      A 39-year-old woman with dyspnea and a productive cough underwent complete
      surgical resection of a small-sized inflammatory myofibroblastic tumor that
      invaded the left main bronchus and the carina with lung-saving modified left one
      stoma-type carinoplasty. We report this case with a review of literature.

PMID- 22880176
TI  - Thymoma of the middle mediastinum.
AB  - Thymoma is a common anterior mediastinal mass, although thymomas have
      occasionally been found in the neck, pulmonary hillus, or posterior mediastinum.
      But a thymoma within the middle mediastinum has rarely been reported. We report a
      thymoma arising in the middle mediastinum with a review of the literature.

PMID- 22880177
TI  - Solitary plasmacytoma of the rib.
AB  - Solitary plasmacytoma of the bone, and especially of a single rib, is a rare
      disease. Here we report a 73-year old male patient complaining of continuous
      chest wall pain around the right 5th rib shaft who underwent a wide excision of
      the rib tumor with surrounding connective tissue. He was diagnosed with solitary
      plasmacytoma and will undergo radiation therapy. We report this case with a
      review of the literature.

PMID- 22880178
TI  - Surgical treatment of killian-jamieson diverticulum.
AB  - Killian-Jamieson diverticulum is a rare diverticular disease. This disease
      differs from Zenker's diverticulum in its location and mechanism. Various
      treatment modality have been attempted, but traditional surgical treatment has
      been recommended for a symptomatic Killian-Jamieson diverticulum due to the
      concern of possible nerve injury. We performed surgical treatment by cervical
      incision. We report here on a case of Killian-Jamieson diverticulum and we
      briefly review the relevant literature.

PMID- 22880179
TI  - Comparison of serum cystatin C and creatinine as a marker for early detection of
      decreasing glomerular filtration rate in renal transplants.
AB  - PURPOSE: We wished to compare the clinical effectiveness of cystatin C (CyC) and
      serum creatinine (sCr) to assess renal function in renal transplantation
      patients. METHODS: We compared the clinical effectiveness of CyC with that of the
      sCr to estimate 24-hour urine creatinine clearance (CrCl) in 72 adult recipients
      who underwent renal transplantation from January 2001 to December 2008. We
      analyzed the data in terms of accuracy, bias, precision and sensitivity as a
      function of length of time posttransplantation and CrCl value. RESULTS: The
      patients were divided into four groups according to CrCl value <30, <60, <90, and
      >=90 mL/min/1.73 m(2). The corresponding Cr-based glomerular filtration rate
      (GFR) estimates had accuracies of 0.71, 0.906, 0.963, and 1.00 within 50% of the
      reference, with biases (mean percentage errors) of 4.7, 5.32, -5.79, -31.33
      mL/min/1.73 m(2), and precisions (mean absolute percentage errors) of 7.57,
      10.03, 14.52, and 31.33 mL/min/1.73 m(2), respectively. The CyC-based GFR
      estimates had accuracies of 0.35, 0.79, 0.93, and 0.67 within 50% of the
      reference, respectively, with biases of 15.03, 13.37, -5.58, and -34.79
      mL/min/1.73 m(2) and precisions of 15.03, 14.80, 17.91, and 34.79 mL/min/1.73
      m(2). The sensitivity for detecting GFR below 60 mL/min/1.73 m(2) was higher for
      CyC (0.96, 1, and 0.95) than for Cr (0.77, 0.75, and 0.82). CONCLUSION: CyC is a
      more sensitive indicator of low GFR (CrCl <60 mL/min/1.73 m(2)) than sCr.
      However, CyC-based GFR estimates are restrictive data, and are neither accurate
      nor specific. Therefore, to evaluate renal function, we may need a revised CyC
      based GFR formula and close monitoring of sCr.

PMID- 22880180
TI  - Impact of preserving the parathyroid glands on hypocalcemia after total
      thyroidectomy with neck dissection.
AB  - PURPOSE: The aims of this study were to determine the incidence and evaluate the
      risk factors for hypocalcemia after total thyroidectomy and to investigate how
      many parathyroid glands should be preserved to prevent postoperative
      hypocalcemia. METHODS: From March 2007 to February 2011, a retrospective review
      of 866 patients who underwent total thyroidectomy and node dissection for thyroid
      cancer was performed. The incidence and predisposing factors for hypocalcemia
      were analyzed. Among them, a total of 191 cases had four of their parathyroid
      glands identified intraoperatively. These patients were then divided into one
      preserved parathyroid gland group (group I, n = 22) and two or more preserved
      parathyroid glands group (group II, n = 169). The incidence of hypocalcemia with
      regards to the number of preserved parathyroid glands was determined and the
      results between the two groups were compared. The total calcium, ionized calcium
      and parathyroid hormone levels were compared between the two groups. RESULTS: The
      overall incidence of transient and permanent hypocalcemia was 9.2% and 0.5%,
      respectively. The decreased number of preserved parathyroid gland and increased
      number of removed central lymph node were the significant risk factors for
      developing postoperative hypocalcemia. In 191 cases identified with four
      parathyroid glands, the incidence of hypocalcemia was related to the number of
      preserved glands (group I, 22.7%; group II, 3.0%; P < 0.001). CONCLUSION: The
      insufficient number of preserved parathyroid glands is the only cause of
      hypocalcemia after total thyroidectomy and node dissection. At least one
      preserved parathyroid gland may prevent postoperative permanent hypocalcemia.

PMID- 22880181
TI  - Preoperative predictors of malignant gastric submucosal tumor.
AB  - PURPOSE: The preoperative prediction of malignant potential in patients with
      gastric submucosal tumors (SMTs) plays an important role in decisions regarding
      their surgical management. METHODS: We evaluated the predictors of malignant
      gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam
      National University Hospital. RESULTS: The malignant SMTs were significantly
      associated with age (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.042
      to 1.091; P < 0.0001), presence of central ulceration (OR, 2.690; 95% CI, 1.224
      to 5.909; P = 0.014), and tumor size (OR, 1.791; 95% CI, 1.483 to 2.164; P <
      0.0001). Receiver operating characteristic curve analysis showed that tumor size
      was a good predictor of malignant potential. The most relevant predictor of
      malignant gastric SMT was tumor size with cut-offs of 4.05 and 6.40 cm.
      CONCLUSION: Our findings indicated that age, central ulceration, and tumor size
      were significant preoperative predictors of malignant SMTs. We suggest that 4 cm
      be selected as a threshold value for malignant gastric SMTs. In patients with a
      gastric SMT larger than 4 cm with ulceration, wide resection of the full
      thickness of the gastric wall or gastrectomy with adequate margins should be
      performed because of its malignant potential.

PMID- 22880182
TI  - Routine barium enema prior to closure of defunctioning ileostomy is not
      necessary.
AB  - PURPOSE: The use of barium enemas to confirm the anastomotic integrity prior to
      ileostomy closure is still controversial. The purpose of the study was to
      determine the utility of routine contrast enema prior to ileostomy closure and
      its impact on patient management in patients with a low pelvic anastomosis.
      METHODS: One hundred forty-five patients had a temporary loop ileostomy
      constructed to protect a low colorectal or coloanal anastomosis following low
      anterior resection for rectal cancer. All patients were evaluated by physical
      examination, proctoscopy, and barium enema prior to ileostomy closure. RESULTS:
      The median time from ileostomy creation to closure was 8 months. Five (3.5%) of
      the 144 patients were found to have clinically relevant strictures at the
      colorectal anastomosis on routine barium enema. One patient (0.7%) showed
      anastomotic leak on their barium enema. Overall, 141 patients (97.9%) had an
      uncomplicated postoperative course. Postoperative complication occurred in three
      patients (2.1%). None of them showed abnormal barium enema finding, which
      suggested that routine contrast enema examination did not predict postoperative
      complication. CONCLUSION: Routine barium enema evaluation of low pelvic
      anastomoses before loop ileostomy closure did not provide any additional
      information for postoperative colorectal anastomotic complication.

PMID- 22880183
TI  - The learning curve for laparoscopic totally extraperitoneal herniorrhaphy by
      moving average.
AB  - PURPOSE: Laparoscopic totally extraperitoneal (TEP) herniorrhaphy has been
      recognized as a treatment option for inguinal hernia. The objective of this study
      was to clarify the learning curve for laparoscopic TEP herniorrhaphy using the
      moving average method. METHODS: A total of 90 patients underwent laparoscopic TEP
      herniorrhaphy by a single surgeon between March 2009 and March 2011. We analyzed
      medical records including the demographic data, operating time, hospital stay,
      and postoperative complications. RESULTS: The mean operating time of the initial
      30 cases (learning period group) was 66.3 minutes. After the initial 30 cases
      were performed, the time decreased to 52.8 minutes in the later 60 cases
      (experienced period group, P = 0.015). This represents the operating time
      becoming stabilized and then decreasing as the number of performed cases
      accumulates. Hospital stay was shorter and frequency of pain control, and
      complication rate were lower in the experienced period, however, there was no
      statistical significance. CONCLUSION: We suggest that number of patients needed
      for the learning curve for laparoscopic TEP herniorrhaphy should be 30 cases. The
      operating time for laparoscopic TEP herniorrhaphy stabilizes after 40 cases in
      moving average analysis.

PMID- 22880184
TI  - Common bile duct dilatation after cholecystectomy: a one-year prospective study.
AB  - PURPOSE: Bile duct dilatation after cholecystectomy continues to be a matter of
      controversy. We aimed determine the magnitude of common bile duct (CBD)
      dilatation after cholecystectomy followed up to 1 year. METHODS: Sixty-four cases
      (age, 47.3 +/- 11.7 years; men, 28; women, 36) enrolled in this study. They
      received laparoscopic cholecystectomy in Chungbuk National University Hospital
      for symptomatic cholelithiasis or gallbladder polyps with normal bile duct, less
      than 7 mm. The CBD diameter was measured by one radiologist using ultrasonography
      at the maximum point after full length evaluation of extrahepatic bile duct.
      Forty-five and thirty-one cases were followed at 6 months and 1 year,
      respectively. RESULTS: The CBD was dilated slightly from 4.1 mm at baseline to
      5.1 mm at 6 months and 6.1 mm at 12 months after cholecystectomy. The number of
      cases of CBD dilatation of more than 7 mm at 6 months and at 12 months after
      cholecystectomy were 11 (24.4%) and 9 (29.0%), respectively. Seven cases at 6
      months and 5 cases at 12 months showed bile duct dilation of more than 3 mm
      compared to baseline. There were no cases having bile duct dilation of more than
      10 mm. CONCLUSION: Postcholecystectomy dilatation of the bile duct occured
      slightly in most cases. But some cases showed more than 3 mm dilatation over
      baseline. Asymptomatic bile duct dilatation of up to 10 mm can be considered as
      normal range in patients after cholecystectomy.

PMID- 22880185
TI  - The surgical experience for retroperitoneal, mesenteric and omental cyst in
      children.
AB  - PURPOSE: Intra-abdominal cystic masses originating from the retroperitoneum,
      mesentery or omentum are very rare and mostly benign tumors, but sometimes
      present as a complicated cyst encasing the major organs. METHODS: We analyzed the
      clinical findings, histologic diagnosis, and surgical outcomes in children who
      underwent operation for retroperitoneal, omental, and mesenteric cyst from 1998
      to 2010, retrospectively. RESULTS: Twenty-three patients (male, 12; female, 11)
      underwent the operation at a median age of 46 months (range, 9 days to 16 years).
      Among them, 17 cysts presented one or two symptoms such as abdominal mass,
      abdominal pain or abdominal distension. The median duration of symptoms was 7
      days (range, 1 day to 365 days). Five were detected prenatally. Ten cysts were
      found in retroperitoneum, 8 in the omentum and 5 in the mesentery. The median
      diameter was 13 cm (range, 3 to 30 cm). Twenty cysts were completely removed.
      Five mesenteric cysts required bowel resection and anastomosis. Three of
      retroperitoneal cysts were impossible to complete excise because of location and
      extensiveness. Pathologically, 20 cysts were lymphangioma and 3 were pseudocyst.
      The morbidity was one of adhesive ileus and the mortality was one who had
      extensive retroperitoneal cyst with mesenteric cyst. He died from sepsis. During
      follow-up period, there was no recurrence. CONCLUSION: Preoperative diagnosis and
      localization for these cysts are very difficult. Complete excision was possible
      in almost all cases despite the size, bringing a favorable outcome. The
      possibility of this disease entity should be considered as the cause of acute
      abdomen.

PMID- 22880186
TI  - Giant sized epidermal inclusion cyst of the breast initially mimicking a large
      fibroadenoma or phyllodes tumor.
AB  - Epidermal inclusion cysts are formed by inclusion of keratinizing squamous
      epithelium within the dermis, resulting in a cyst filled with lamellated keratin.
      These benign cysts are usually very small and intradermal subcutaneous lesions.
      They can occur anywhere in the body although they are more common on the face,
      trunk, neck, extremities and scalp. Only a few cases of epidermal cysts of the
      breast have been reported in the literature. An epidermal inclusion cyst of the
      breast can result in several problems, even if the size is unusual. We
      encountered a case of a giant sized epidermal inclusion cyst of the breast
      initially mimicking a large fibroadenoma or phyllodes tumor.

PMID- 22880187
TI  - Primary gastric Hodgkin's lymphoma.
AB  - Gastric Hodgkin's lymphoma is extremely rare. We present a case of primary
      Hodgkin's lymphoma arising in the stomach of a 65-year-old woman. The patient
      complained of epigastric discomfort and reflux for one month. Endoscopic
      examination revealed a protruding lesion characterized by a smooth surface at the
      antrum. An abdominal computed tomography uncovered a 2.5 * 2.0 cm, exophytic
      submucosal mass. After the tentative preoperative diagnosis of a gastrointestinal
      stromal tumor, a gastric wedge resection was performed. Microscopic examination
      of the mass demonstrated a diffuse proliferation of large atypical lymphoid cells
      with mono- and binucleated pleomorphic nuclei and prominent nucleoli.
      Immunohistochemically, the tumor cells were positive for CD30, CD20, and CD79a,
      whereas they were negative for cytokeratin, carcinoembryonic antigen, CD3, CD15,
      epithelial membrane antigen, and anaplastic lymphoma kinase-1. Based on the
      morphological features and immunohistochemical results, in addition to the
      clinical findings, a diagnosis of primary gastric Hodgkin's lymphoma was
      established.

PMID- 22880188
TI  - Successful aspiration and thrombolytic therapy for acute superior mesenteric
      artery occlusion.
AB  - To report a case of acute superior mesenteric artery (SMA) embolism successfully
      treated with aspiration and pharmacological thrombolysis. A 74-year-old female
      was admitted to the hospital with acute abdominal pain 5 hours in duration.
      Computed tomography angiography revealed a complete embolic occlusion distal to
      the first jejunal branch of the SMA. Aspiration and local continuous thrombolysis
      with urokinase resulted in near complete revascularization of the mesenteric flow
      after 4 hours and almost complete restoration after 20 hours. The patient made a
      complete recovery and continues to do well on warfarin therapy after treatment.
      Aspiration and thrombolytic therapy can be an alternative treatment modality in
      surgical high risk patient.

PMID- 22880189
TI  - Damage control surgery in patient with delayed rupture of pseudoaneurysm after
      blunt abdominal trauma.
AB  - Delayed rupture of post-traumatic pseudoaneurysms of the visceral arteries,
      especially the pancreaticoduodenal artery, is uncommon. Here, we describe a 55
      year-old man hemorrhaging from a pseudoaneurysm of the inferior
      pancreaticoduodenal artery (IPDA). Computed tomography of the abdomen showed
      active bleeding in the IPDA and large amounts of hemoperitoneum and
      hemoretroperitoneum. Selective mesenteric angiography showed that the
      pseudoaneurysm arose from the IPDA, and treatment by angioembolization failed
      because the involved artery was too tortuous to fit with a catheter. Damage
      control surgery with surgical ligation and pad packing was successfully
      performed. The patient had an uncomplicated postoperative course and was
      discharged 19 days after the operation. To our knowledge, this is the first
      report of ruptured pseudoaneurysm of an IPDA after blunt abdominal trauma from
      Korea.

PMID- 22880190
TI  - [Review of recommendations and new diagnosis criteria for mild cognitive
      impairment due to Alzheimer's disease].
AB  - The symptomatic predementia phase of Alzheimer's disease (AD), known as mild
      cognitive impairment (MCI) is a clinical and neuropsychological condition which
      defines the transitional state between normal aging and dementia, and is used as
      a clinical description of people at risk of developing AD. A review of the
      diagnostic criteria of MCI due to Alzheimer's disease was recently published by
      the Alzheimer's Association and the National Institute on Aging of the U.S. in
      order to ensure early diagnosis of the disease, useful for both clinical practice
      and clinical trials. The objectives of this paper are to review and analyze the
      revised diagnostic criteria for MCI due to Alzheimer's disease recently proposed,
      to compare with criteria for MCI available and to establish current strengths and
      limitations of the new proposal in clinical practice. The new diagnostic criteria
      for MCI due to AD have a radical importance since they are potentially applicable
      in the clinical or research protocols and in all clinical settings where such
      markers are available. They provide a useful, consistent and valuable tool to
      homogenize the subgroup of patients with MCI who already has AD in a predementia
      phase with inexorable progression to dementia by AD over the years.

PMID- 22880191
TI  - [Mental health as seen from a psychiatric standpoint].
AB  - This paper proposes a psychiatric perspective on mental health given by many
      years of experience and confrontation with many clinical forms in which the lost
      of mental health is expressed. This lost brings by effects on those who suffer it
      as well as on their relatives. The mental health law of Argentina 26657 is
      analyzed from this particular standpoint. It is recognized that its spirit is
      part of an ecumenical movement which stimulates inclusion and full citizenship
      for all the people, even for minorities such as mentally ill patients. It is also
      proposed that some of the ideological origins are traceable back to critical
      trends within psychiatry and that a lack of academic and professional consult at
      the moment of its redaction has generated an unnecessary dispute despite
      important agreements on the spirit of the law.

PMID- 22880192
TI  - [The concept of Mental Health from the perspective of Occupational Therapy].
AB  - The focus of this text is to share the way we think and organize information in
      order to build our perspective of Mental Health from Occupational Therapy on the
      basis of our academic instruction. We use the word "building" because we
      understand this as a dynamic, flexible, and ever changing process in which the
      Occupational Therapist implement diverse verbal and material resources according
      to the moment in the Health-Disease process. We hope that this revision will
      offer a specific view of the meaning of "doing" from the Occupational Therapy
      perspective; process that implies different stages in a permanent reflection
      between theory and praxis. The main purpose is that persons, groups or
      communities reach the best opportunities of autonomy and quality of life. We will
      cover notions about risk and psychosocial dysfunction in articulation with the
      International Classification of Functioning, Disability and Health (ICF) followed
      by the paradigm that have transformed our clinical practice in every level in
      which Occupational Therapy intervenes. We do not pretend to arrive to conclusions
      but to question certain ideas that we have inherited from other health
      disciplines like: chronic/acute; adapted/mis-adapted; disqualified/
      rehabilitated, and that have influenced our profession.

PMID- 22880193
TI  - [The museum of the longings of reason].
AB  - The paths of mental health and psychoanalysis diverge. The path of mental health
      is to frame hu-man behavior into "normality". It is in the idea of "public order"
      and in "the correct way" where is to be found. The second is concerned with the
      particularity of each subject and, finally, with its singularity. The "sinthome"
      is the key to this difference. The "sinthome" can be understood as a dysfunction
      which is to be corrected to reestablish the submission to the norm or as a
      "truth" to be revealed as the way to the most singular of each subject. It is in
      this point where we will find a cer-tainty of being "beyond neurosis" which will
      orientate each individual in the way of dignity, which is not necessarily that of
      wellbeing.

PMID- 22880194
TI  - [The intervention of the social work in the mental health field. Some
      interrogations and perspectives].
AB  - The intervention of the Social Work in the Mental Health field has singular
      characteristics. These relate to the social current scenes in which arises the
      need to recover the notion of historical social process to understand and to
      explain with major depth the complexity of the context. These matters express
      from the subjective suffering up to the Sanitary and Social Policies. The
      recovery of the notion of biopolitic and a social reading of the corporal thing,
      the narratives of the pain and the mental health, realize of the possibilities
      and scopes of the intervention in the social thing inside this field. The current
      demands towards the sector, understood like Problematic Social Complex, show
      another paths into both for the conceptualization of situations as for the
      intervention on they. At the same time, the actions inside the field of the
      health interlace in direct or indirect form with a series of new logics inside
      the social policies that link themselves with the notion of social inclusion.
      Also the most recent changes mark a new configuration of neighborhood and
      community, now understood from the notion of territory. The intervention from the
      Social Work from this perspective implies a new and necessary place for the word.

PMID- 22880195
TI  - [Mental Health and relationships].
AB  - After acknowledging that the diversity of cultural, historical and theoretical
      perspectives has given place to multiple definitions of mental health, the author
      circumscribes the goal of this article to reflecting on mental health from the
      viewpoint of human relationships in intersubjective milieux. The basic assumption
      that guides this paper is that the subject's psychic structure is constituted and
      developed in a relational matrix. Conceptualized in a relational context, the
      individual's mental health needs to take into account each member's developmental
      stage and asymmetrical position in a relationship. In the theoretical and
      therapeutic approach proposed here, drive renunciation, negative pacts, and
      intersubjective work are described as basic concepts in the analysis of
      relational links. Drive renunciation is defined as the operation that excludes
      certain drives derivatives from explicit relational interchange in order to
      maintain the structure and stability of the relationship. Negative pacts are
      defined as the configurations of reciprocal libidinal investments that give form
      to drive renunciation. The concept of intersubjective work places the emphasis on
      the interaction of the poles of the relationship, on how what one does influences
      the other's response. Thus, in the therapeutic context, intersubjective work
      accounts for each member's processes of symbolization and working through in the
      interchange and reciprocal impact of each member on the transformation of the
      relationship. Finally, the complexities around the formulation of therapeutic
      goals are emphasized and the occasional need of an interdisciplinary therapeutic
      plan is highlighted.

PMID- 22880196
TI  - [Mental health from a cognitive-behavioral perspective].
AB  - This paper presents a succinct overview of the conception of mental health held
      by the cognitive-behavioral paradigm. For some of these models, human suffering
      is ubiquitious and largely unavoidable. Therefore, suffering cannot be linearly
      equated to pathology. Mental health implies acting towards achieving our valued
      goals, despite the negative emotions and thoughts that this may activate. The
      paper describes some cognitive and metacognitive phenomena characteristically
      associated to psychopathology, as well as some principles to establish the
      normalcy of both emotional experience and behavior. It establishes a difference
      between consultations motivated by mental disorders and those motivated by life
      crises and by a desire of achieving personal growth. Finally, the paper analyzes
      the conditions in which implementing treatment is desirable and necessary.

PMID- 22880197
TI  - [Conceptualizing mental health into practice: considerations from the Latin
      American social medicine/collective health perspective].
AB  - The aim of this work is to discuss about the possibilities of a mental health
      definition from the perspective of the Latin American social medicine/collective
      health movement. Some relations between that movement and the mental health are
      pointed out. A historical analysis of that movement is presented. The
      conceptualizations of the health-sickness-care process are considered,
      emphasizing the complexity, rights perspective and the reference to life, in
      contrast with the objetivation/medicalization trend. Finally, these ideas are
      linked with the current debates on the Mental Health field.

PMID- 22880198
TI  - [New paradigms in mental health and the vision from music therapy].
AB  - This paper aims to describe the vision of mental health from the standpoint of
      music therapy, framed by the National Law 26.567. First, basic notions about the
      origins of this discipline are introduced, as well as the criteria that inform
      its practice and the tools used by this approach, listening, analysis and the
      intervention in the mental health field. Later, the concepts of music therapy
      intervention and creative process are highlighted, providing some characteristics
      of the relationships that may arise between each of them and the mental health.

PMID- 22880199
TI  - [The occupational therapist's role in an interdisciplinary team within the
      Rehabilitation and External Aids Program].
AB  - The role of an occupational therapist in the Mental Health team, particularly in
      the Rehabilitation and Assisted Discharge Program (PREA), is to provide a focus
      on the person and on a meaningful occupation for him. The interdisciplinary team
      of each device, involving an occupational therapist, performs planning goals and
      implementing the means to achieve through strategies of psychosocial
      rehabilitation. Meanwhile, intervention strategies are developed and individual
      support for each person is given to carry out a project of life in the community,
      building a social, occupational and significant work in order to enhance users'
      recovery.

PMID- 22880200
TI  - Dispersive liquid-liquid microextraction using functionalized Mg(OH)2 NPs with
      oleic acid as hydrophobic affinity probes for the analysis of hydrophobic
      proteins in bacteria by MALDI MS.
AB  - We report a dispersive liquid-liquid microextraction (LLME) method using surface
      modified Mg(OH)(2) nanoparticles (NPs) with oleic acid (OA) as hydrophobic
      affinity probes for the extraction and preconcentration of hydrophobic
      biomolecules prior to MALDI MS analysis. OA-capped Mg(OH)(2) NPs were
      characterized by FT-IR, SEM and TEM. The functionalized Mg(OH)(2) NPs are well
      dispersed in toluene with an average diameter of <35 nm. Under the optimum
      conditions, the method showed good linearity in the ranges of 10-400 nM and 0. 1
      2.0 MUM for valinomycin and gramicidin D, respectively. The limits of detection
      were in the region of 2.0 nM and 24 nM for valinomycin and gramicidin D,
      respectively. Moreover, the OA-capped Mg(OH)(2) NPs-assisted LLME method was
      successfully used for the rapid extraction/preconcentration of hydrophobic
      proteins in bacteria (Escherichia coli and Bacillus subtilis) prior to their
      identification by MALDI MS.

PMID- 22880201
TI  - A first step towards the understanding of the 5-HT3 receptor subunit
      heterogeneity from a computational point of view.
AB  - The functional serotonin type-3 receptor (5-HT(3)-R), which is the target of many
      neuroactive drugs, is known to be a homopentamer made of five identical subunits
      A (5-HT(3A)-R) or a binary heteropentamer made of subunits A and B (5-HT(3A/B)-R)
      with a still debated arrangement and stoichiometry. This complex picture has been
      recently further complicated by the discovery of additional 5-HT(3)-R subunits,
      C, D, and E, which, similarly to the B subunit, are apparently able to form
      functional receptors only if co-expressed with subunit A. Being the binding site
      for both serotonin and antagonists (i.e. drugs) located at the extracellular
      interface between two adjacent subunits, the large variability of the 5-HT(3)-R
      composition becomes a crucial issue, since it can originate many different
      interfaces providing non-equivalent ligand binding sites and complicating the
      pharmacological modulation. Here, the different 5-HT(3)-R interfaces are
      analysed, on the bases of the structural conformations of previously built 3D
      homology models and of the known subunit sequences, by addressing their
      physicochemical characterization. The results confirm the presence of an aromatic
      cluster located in the core of the A-A interface as a key determinant for having
      an interface both stable and functional. This is used as a discriminant to make
      hypotheses about the capability of all the other possible interfaces constituted
      by the known 5-HT(3)-R sequences A, B, C, D, and E to build active receptors.

PMID- 22880202
TI  - Photoinduced water splitting with oxotitanium porphyrin: a computational study.
AB  - The photochemistry of the hydrogen-bonded oxotitanium porphyrin-water complex
      (TiOP-H(2)O) has been explored with electronic-structure calculations. It is
      shown that intramolecular charge-transfer processes, which are initiated by the
      excitation of the Soret band of TiOP, accumulate electronic charge on the oxygen
      atom of TiOP, which in turn abstracts a hydrogen atom from water by an
      exoenergetic and essentially barrierless hydrogen-transfer reaction, resulting in
      the TiPOH-OH biradical. About 75% of the absorbed photon energy is thus stored as
      chemical energy in two ground-state radicals. Absorption of a second photon by
      TiPOH can result in the detachment of the H radical and recovery of the
      photocatalyzer TiOP. Again, about 75% of the photon energy is stored in the
      dissociation energy of TiPOH. Overall, a water molecule is decomposed into H and
      OH radicals by the absorption of two visible photons. Exoenergetic radical
      recombination reactions can yield molecular hydrogen, molecular oxygen or
      hydrogen peroxide as closed-shell products.

PMID- 22880203
TI  - Patchy worm-like micelles: solution structure studied by small-angle neutron
      scattering.
AB  - Triblock terpolymers exhibit a rich self-organization behavior including the
      formation of fascinating cylindrical core-shell structures with a phase separated
      corona. After crystallization-induced self-assembly of polystyrene-block
      polyethylene-block-poly(methyl methacrylate) triblock terpolymers (abbreviated as
      SEMs = Styrene-Ethylene-Methacrylates) from solution, worm-like core-shell
      micelles with a patchy corona of polystyrene and poly(methyl methacrylate) were
      observed by transmission electron microscopy. However, the solution structure is
      still a matter of debate. Here, we present a method to distinguish in situ
      between a Janus-type (two faced) and a patchy (multiple compartments)
      configuration of the corona. To discriminate between both models the scattering
      intensity must be determined mainly by one corona compartment. Contrast variation
      in small-angle neutron scattering enables us to focus on one compartment of the
      worm-like micelles. The results validate the existence of the patchy structure
      also in solution.

PMID- 22880204
TI  - In situ synthesized heteropoly acid/polyaniline/graphene nanocomposites to
      simultaneously boost both double layer- and pseudo-capacitance for
      supercapacitors.
AB  - It is challenging to simultaneously increase double layer- and pseudo-capacitance
      for supercapacitors. Phosphomolybdic acid/polyaniline/graphene nanocomposites
      (PMo(12)-PANI/GS) were prepared by using PMo(12) as a bifunctional reagent for
      not only well dispersing graphene for high electrochemical double layer
      capacitance but also in situ chemically polymerizing aniline for high
      pseudocapacitance, resulting in a specific capacitance of 587 F g(-1), which is
      ~1.5 and 6 times higher than that of PANI/GS (392 F g(-1)) and GS (103 F g(-1)),
      respectively. The nanocomposites also exhibit good reversibility and stability.
      Other kinds of heteropolyacids such as molybdovanadophosphoric acids (PMo(12
      x)V(x), x = 1, 2 and 3) were also used to prepare PMo(12-x)V(x)-PANI/GS
      nanocomposites, also showing enhanced double layer- and pseudo-capacitance. This
      further proves the proposed concept to simultaneously boost both double layer-
      and pseudo-capacitance and demonstrates that it could be a universal approach to
      significantly improve the capacitance for supercapacitors.

PMID- 22880205
TI  - High capacity of an Fe-air rechargeable battery using LaGaO3-based oxide ion
      conductor as an electrolyte.
AB  - Rapid growth and improved functions of mobile equipment present the need for an
      advanced rechargeable battery with extremely high capacity. In this study, we
      investigated the application of fuel cell technology to an Fe-air rechargeable
      battery. Because the redox potential of Fe is similar to that of H(2), the
      combination of H(2) formation by the oxidation of Fe with a fuel cell has led to
      a new type of metal-air rechargeable battery. By decreasing the operating
      temperature, a deep oxidation state of Fe can be achieved, resulting in enlarged
      capacity of the Fe-air battery. We found that the metal Fe is oxidized to
      Fe(3)O(4) by using H(2)/H(2)O as mediator. The observed discharge capacity is 817
      mA h g(-1)-Fe, which is approximately 68% of the theoretical capacity of the
      formation of Fe(3)O(4), 1200 mA h g(-1)-Fe, at 10 mA cm(-2) and 873 K. Moreover,
      the cycle stability of this cell is examined. At 1073 K, the cell shows a
      discharge capacity of ca. 800 mA h g(-1)-Fe with reasonably high discharge
      capacity sustained over five cycles.

PMID- 22880207
TI  - Laboratory studies of photochemistry and gas phase radical reaction kinetics
      relevant to planetary atmospheres.
AB  - This review seeks to bring together a selection of recent laboratory work on gas
      phase photochemistry, kinetics and reaction dynamics of radical species relevant
      to the understanding of planetary atmospheres other than that of Earth. A
      majority of work focuses on the rich organic chemistry associated with
      photochemically initiated reactions in the upper atmospheres of the giant
      planets. Reactions relevant to Titan, the largest moon of Saturn and with a
      nitrogen/methane dominated atmosphere, have also received much focus due to
      potential to explain the chemistry of Earth's prebiotic atmosphere. Analogies are
      drawn between the approaches of terrestrial and non-terrestrial atmospheric
      chemistry.

PMID- 22880206
TI  - Natural supramolecular building blocks: from virus coat proteins to viral
      nanoparticles.
AB  - Viruses belong to a fascinating class of natural supramolecular structures,
      composed of multiple copies of coat proteins (CPs) that assemble into different
      shapes with a variety of sizes from tens to hundreds of nanometres. Because of
      their advantages including simple/economic production, well-defined structural
      features, unique shapes and sizes, genetic programmability and robust
      chemistries, recently viruses and virus-like nanoparticles (VLPs) have been used
      widely in biomedical applications and materials synthesis. In this critical
      review, we highlight recent advances in the use of virus coat proteins (VCPs) and
      viral nanoparticles (VNPs) as building blocks in self-assembly studies and
      materials development. We first discuss the self-assembly of VCPs into VLPs,
      which can efficiently incorporate a variety of different materials as cores
      inside the viral protein shells. Then, the self-assembly of VNPs at surfaces or
      interfaces is summarized. Finally, we discuss the co-assembly of VNPs with
      different functional materials (178 references).

PMID- 22880208
TI  - Mechanical performance of cylindrical and dual-core pedicle screws after repeated
      insertion.
AB  - STUDY DESIGN: Ex vivo study of the mechanical performance of cylindrical and dual
      core pedicle screws after insertion, removal, and reinsertion in the same hole.
      OBJECTIVE: To evaluate the effect of repeated use of same screw hole on the
      insertion torque and the retentive strength of the cylindrical and dual-core
      screws. SUMMARY OF BACKGROUND DATA: Insertion and removal of pedicle screws is
      sometimes necessary during surgical procedure to assess the integrity of the
      pilot-hole wall. However, this maneuver may compromise the implant-holding
      capacity. METHODS: Sixty thoracolombar vertebrae (T13-L5), harvested from 10
      healthy calves, were used to insert 2 different designs of pedicle screws:
      cylindrical (5.0-mm outer diameter) and dual-core screws (5.2-mm outer diameter).
      Three experimental groups were created on the basis of the number of insertions
      of the screws and 2 subgroups were established according to the core pedicle
      screw design (dual-core and cylindrical). The insertion torque was measured
      during initial insertion, second insertion, and third insertion. Pullout screw
      tests were performed using a universal testing machine to evaluate the pullout
      strength after initial insertion, second insertion, and third insertion. RESULTS:
      Significant reductions of 38% in mean insertion torque and 30% in mean pullout
      strength of dual-core screw were observed between the initial insertion and the
      third insertion. The cylindrical screw observed significant reductions of 52.5%
      in mean insertion torque and 42.3% in mean pullout strength between the initial
      insertion and the third insertion. A reduction of mean insertion torque and
      pullout strength between the first insertion and the second insertion but without
      significance was also observed for both types of screws. CONCLUSION: Insertions
      and reinsertion of either cylindrical or dual-core pedicle screws have
      compromised insertion torque and pullout strength of the implants as measured by
      mechanical tests.

PMID- 22880209
TI  - Job applications: Straight to the top of the pile.

PMID- 22880210
TI  - Cardiac electrophysiology in New Zealand: a small but vital speciality.
AB  - Dr Martin Stiles talks about the electrophysiology scene in NZ with Iona
      MacDonald.

PMID- 22880211
TI  - Novel oral anticoagulants for stroke prevention in atrial fibrillation.

PMID- 22880212
TI  - The Polish Cardiac Society. The president discusses the aims and achievements of
      one of the largest national societies in the ESC.

PMID- 22880213
TI  - South Africa Heart Journal. Striving to be the best cardiovascular medicine
      journal on the African continent.

PMID- 22880215
TI  - Out of the wilderness.

PMID- 22880216
TI  - States' transparency rules fall short of members' needs.

PMID- 22880214
TI  - Remote ischaemic preconditioning for heart surgery. The study design for a multi
      center randomized double-blinded controlled clinical trial--the RIPHeart-Study.
AB  - AIMS: Transient ischaemia of non-vital tissue has been shown to enhance the
      tolerance of remote organs to cope with a subsequent prolonged ischaemic event in
      a number of clinical conditions, a phenomenon known as remote ischaemic
      preconditioning (RIPC). However, there remains uncertainty about the efficacy of
      RIPC in patients undergoing cardiac surgery. The purpose of this report is to
      describe the design and methods used in the "Remote Ischaemic Preconditioning for
      Heart Surgery (RIPHeart)-Study". METHODS: We are conducting a prospective,
      randomized, double-blind, multicentre, controlled trial including 2070 adult
      cardiac surgical patients. All types of surgery in which cardiopulmonary bypass
      is used will be included. Patients will be randomized either to the RIPC group
      receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to
      the control group receiving four cycles of blood pressure cuff
      inflation/deflation at a dummy arm. The primary endpoint is a composite outcome
      (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or
      acute renal failure) until hospital discharge. CONCLUSION: The RIPHeart-Study is
      a multicentre trial to determine whether RIPC may improve clinical outcome in
      cardiac surgical patients.

PMID- 22880217
TI  - Modest pay increase seen for chief nursing officers.

PMID- 22880218
TI  - CE research often ignores payers' concerns.

PMID- 22880219
TI  - Specialty drugs to spark next round of cost increases.

PMID- 22880220
TI  - [Central nerves system tumor].

PMID- 22880221
TI  - [I. Treatment and problem of primary central nerve system lymphoma].

PMID- 22880222
TI  - [II. Primary treatment of CNS lymphoma with high-dose MTX].

PMID- 22880223
TI  - [III. Treatment of recurrent primary central nerve system lymphoma].

PMID- 22880224
TI  - Rio+20: (Un)sustainability and public health.

PMID- 22880225
TI  - Grumblers in the time of Diagnosis-Related Groups: sand in the gear or
      lubricating oil?
AB  - OBJECTIVE: After the change from cost allowance to a German system of Diagnosis
      Related Groups there has been much public discussion about how the new terms of
      employment within the health sector are increasingly in conflict with
      individuals'original motivations for their career choice. If such criticism
      remains unheard a further loss of employees might occur. METHODS: Two decades of
      professional experiences have been reviewed. The results were personally assessed
      and summarized in a field report. PARTICIPANTS: One senior physician, Department
      of Anesthesiology, University Hospital. RESULTS: In total, a deliberate contact
      approach by management to address employees' criticisms and grumbling about the
      terms of employment is essential for enterprise's success. CONCLUSIONS: While
      employees can introduce criticisms more constructively to contribute ideas that
      protect the enterprise'ssuccess, executives will have to position themselves in
      such a way as to be open to these perspectives. Constructive contact with
      "hospital troublemakers" should be implemented into the enterprise culture.
      Guidance is necessary to institute such changes.

PMID- 22880226
TI  - [Functional analysis for dysfibrinogenemias, Toyama and Adachi, which have a
      mutation of Aalpha16Arg-->His (CGT-->CAT) with aberrant fibrinopeptide A
      release].
AB  - We found and identified four heterozygous dysfibrinogenemias with AalphaR16H(CGT-
      >CAT) mutation in two families by coagulation tests and direct sequence analysis
      for PCR-amplified DNA fragments. Two dysfibrinogens were designated as fibrinogen
      Toyama and Adachi, according to the place of residence of proposituses,
      respectively. Patients' fibrinogen purified from plasma using immunoaffinity
      chromatography was subjected to thrombin- or batroxobin-catalyzed fibrin
      polymerization, fibrinopeptide A (FPA) release, and clottability test. AalphaR16H
      fibrinogen showed impaired thrombin or batroxobin-catalyzed fibrin polymerization
      in comparison with normal control fibrinogen. It is interesting that the period
      of protofibril formation of Toyama propositus was longest in those of four
      affected people. The clottability of AalphaR16H-fibrinogen was 66-70% with
      thrombin and higher than with batroxobin, 35-50%. In the same condition with
      fibrin polymerization, thrombin and batroxobin did not cleave the Aalpha16H-17G
      peptide-bonding, resulting in no release of variant FPA. From these results, we
      speculated that elongation of the two-stranded protofibril formation would be
      terminated by participation of the heterodimer fibrinogen molecules composed with
      a normal and an aberrant Aalpha-chain, and it would result in a decrease in
      fibrin polymerization. We speculated that the difference in the extent of
      impairment of fibrin polymerization among the patients might be caused by the
      different amount of heterodimers. Moreover, we also speculated that batroxobin
      induced clottability was lower than thrombin-induced clottability, because
      batroxobin cannot induce the so-called "B-knob-b-hole" interaction, which
      enhances fibrin formation.

PMID- 22880227
TI  - Characterization of two mobilizable plasmids isolated from enterobacter cloacae.
AB  - We isolated two plasmids, pS51A and pS51B which were 5782 bp and 4854 bp in size,
      respectively, from the third generation cephalosporin-resistant E. cloacae
      suspected to express metallo-beta-lactamase, and analyzed their structures. These
      two plasmids encode RNA I/RNA II genes for replication origin, relaxase genes of
      mobABCD for plasmid transfer, and several open reading frames. According to the
      classification of mobilizable plasmids by gene organization of the relaxases,
      pS51A and pS51B belong to the ColE1 superfamily of mobilizable plasmids, commonly
      detected in Enterobacteriaceae. The metallo-beta-lactamase gene was not
      identified in either pS51A or pS51B by homology search of the putative open
      reading frames. Open reading frames encoded in pS51A include E. coli protein L
      like, E. coli heat shock protein-like, and E. coli plasmid replication initiation
      protein-like, and those encoded in pS51B include helix-turn-helix protein-like,
      E. coli plasmid replication initiation protein-like, and Salmonella replication
      initiation protein-like. These plasmids are stably maintained in one strain of E.
      cloacae, thus, the encoded gene functions may confer growth advantage to the host
      cell.

PMID- 22880228
TI  - [Draft proposal to estimate true values of serum potassium in samples from
      patients with myeloproliferative neoplasma].
AB  - The pseudohyperkalemia in thrombocytosis is assumed to be due to potassium
      released from blood cells during blood clotting as reported previously, but its
      mechanisms remain to be cleared. Although plasma potassium measurements with
      blood collection tubes containing heparin are performed in many hospitals to
      avoid pseudohyperkalemia, the burden on patients may come out with further blood
      sampling by another heparinized tube. Taken together, we investigated laboratory
      data possibly involved in pseudohyperkalemia in 184 samples from patients with
      myeloproliferative neoplasma (MPN), and studied estimation capability for true
      values of serum potassium, driving a correction formula by means of several
      laboratory data to explain the difference of measured potassium values (K
      difference: serum value minus plasma value). Platelet count and mean corpuscular
      volume (MCV) were adopted as significant variables correlated to K-difference as
      a result of multiple regression analysis. A correction formula was driven by
      multiple regression equation with these two variables as follows: y = 0.0006 x
      1+0.0004 x 2-0.177 (r= 0.885; x 1, platelet count; x 2, MPV). The correction
      formula was considered to be useful for estimating the true value of serum
      potassium in samples from patients with MPN because the corrected serum potassium
      value correlated highly with plasma potassium value (r = 0.885). These results
      propose that true values of serum potassium can be estimated by the correction of
      measured serum potassium values with platelet count and MCV, suggesting that not
      only quantitative factors but also qualitative factors may be involved in
      pseudohyperkalemia.

PMID- 22880229
TI  - [Establishment of multiplex hybri-probe method--analysis using the polymorphism
      of UGT1A1 gene].
AB  - There are a number of methods for gene analysis of a point mutation and
      deletion/insertion of several nucleotides. In 2011, we reported an improved
      hybridization probe methods (Hybri-Probe method) that are highly sensitive and
      accurate, and excellent in cost and time effectiveness. Here, we have developed
      the Multiplex Hybri Probe method for several types of mutations or polymorphisms
      including the microsatellite polymorphisms, especially of palindromic sequence
      such as (TA)n and (GC)n. In addition, several mutations are analyzed at a time.
      In this research we focused on the three types of polymorphism on the Uridine
      diphosphate glucuronyltransferase (UGT) gene. Design of the probes for the
      detection of UGT1A1*6(211 G --> A G71R) and UGT1A1*27 (686 C --> A P229Q) was not
      difficult because the mutations were a single base substitution. However,
      UGT1A1*28 (A (TA)6TAA --> A (TA)7TAA) has tandem and palindromic sequence. Since
      the probes to detect the mutation in such sequence resulted in failure, we made
      several mismatches, i.e., TATATATATATA --> TATGTGTATATA. As a result, the probes
      designed for the three polymorphisms above did not overlap in the Tm and were
      separated by approximately 10 degree intervals between 63.2 degrees C and 37.5
      degrees C. In this Multiplex Hybri-Probe method, the three kinds of probe are
      added tube into the PCR product in the same tube and followed by the measurement
      of the Tm using the LightCycler. Thus, it is very simple, and performed by one
      step for any mutation including the microsatellite polymorphisms, and it also has
      good cost performance and favorable time efficiency. It takes two hours including
      the running time of PCR for completion of the analysis. It may also be available
      to the detection of other gene abnormalities.

PMID- 22880230
TI  - Waldenstrom macroglobulinemia transforming from t (11;18) (q21;q21) -negative
      gastric MALT lymphoma after systemic dissemination.
AB  - AIM: We here describe the clinical course of a 70-year-old male patient with
      Waldenstrom macroglobulinemia (WM) putatively transformed from refractory mucosa
      associated lymphoid tissue lymphoma (MALTL). METHODS: Immunological staining was
      performed on formalin-fixed, paraffin-embedded tissue sections, and M-protein and
      cryoglobulin were identified by immunofixation electrophoresis and the cold
      precipitation method. Chromosome translocation was analyzed by the G-banded
      karyotype, and API2/MALT1 fusion gene underwent fluorescent in situ
      hybridization. Multiplex polymerase chain reaction was performed to analyze the
      VH-JH or DH-JH rearrangements of the IGH gene. RESULTS: At diagnosis, the WM
      patient had monoclonal IgM with cryoglobulinemia and hyperviscosity syndrome.
      Eight years before developing WM, the patient experienced the onset of typical
      gastric MALT-L with H. pylori infection, but in spite of negative for chromosome
      translocation, t (11;18) and the successful eradication of H. pylori, the MALT-L
      relapsed repeatedly, and finally led to systemic metastasis. The lymphoma cells
      also infiltrated the large intestine and spleen. Immunoglobulin gene analyses of
      cellular clonality revealed that the same clone had been present in the stomach,
      bone marrow (BM) at the onset of MALT L, and in the BM at the diagnosis of WM.
      CONCLUSIONS: In this case, lymphoma developed as H. pylori-associated gastric
      MALT-L with negative for t (11;18), and might be transformed into MW during the
      systemic metastasis.

PMID- 22880231
TI  - [Studies on the development of clinical laboratory tests by mathematical
      approaches: final lecture].
AB  - This is a forty-year story of my study of the development of clinical laboratory
      tests by mathematical approaches. First, I developed a digital filter which could
      remove components other than those of the QRS complex from a recorded
      electrocardiogram. This method is called the Okada algorithm and has been cited
      by many papers. Next, I studied the application of information theory and
      developed a function to reduce the amount of clinical data by eliminating
      relatively insignificant data items. This function was derived to give the
      minimum information quantity for the relative significance. The computed values
      were defined as "weighted entropy". During the last two decades, I have occupied
      myself with studies of clinical biochemistry. By investigating interactions
      between lipoproteins and surfactants, divalent cations, sugars, and lectins, we
      developed a new assay protocol to chemically measure the LDL cholesterol level in
      serum that does not require immunoseparation or centrifugation. The accuracy and
      precision of our assay protocol fulfilled the criteria of the NCEP Lipid
      Standardization Panel. The experimental data showed that our assay protocol was
      superior to the Friedewald formula. Also, I developed a homogeneous assay
      protocol to directly measure triglyceride content in VLDL. Possible reagents and
      conditions for measuring VLDL-TG were comprehensively tested, and the "best"
      combination was determined. Our data showed that the homogeneous method could
      successfully measure triglyceride content in VLDL particles. I hope that my
      experience of these studies will inspire younger investigators in the field.

PMID- 22880232
TI  - [Diagnosis and management of antibiotic-resistant bacteria].
AB  - Antibiotic-resistant infections acquired in hospitals are of great concern, and
      have become a serious public issue. Antibiotic-resistant infections can be
      associated with a variety of bacteria, such as methicillin resistant
      Staphylococcus aureus(MRSA) and multidrug-resistant Pseudomonas aeruginosa
      (MDRP). Since clinical laboratories are responsible for detecting information
      regarding antibiotic-resistant bacteria, they are required to perform analysis
      and dissemination of the information. Currently, rapid methods for detecting
      antibiotic-resistant bacteria using molecular techniques are being developed in
      response to the problem of the conventional methods for bacteriological testing,
      which require a few days to obtain results. This article presents the diagnosis
      and management of antibiotic-resistant bacteria, which comprise a serious health
      care issue.

PMID- 22880233
TI  - [Classification and diagnosis of essential thrombocythemia].
AB  - Although the fourth edition of the World Health Organization (WHO) classification
      of the diagnostic criteria for myeloproliferative neoplasms is widely accepted,
      the diagnosis of essential thrombocythemia has been debated. One of the
      controversies focuses on the provisional entity known as refractory anemia, which
      exhibits ringed sideroblasts associated with marked thrombocytosis (RARS-T). To
      date, it has not been made clear whether RARS-T is a form of ET or a separate and
      unique disease entity. Recent findings, which may shed light on this debate, have
      demonstrated that more than 60% of RARS-T patients exhibit somatic mutations of
      SF3B1, a gene encoding a core component of the RNA-splicing system. Another
      debate is focused on the role of bone marrow histopathology in the diagnosis of
      essential thrombocythemia. Bone marrow histopathology has been considered to be a
      major diagnostic criterion for essential thrombocythemia since the previous
      version of the WHO classification criteria was published. The histological
      features of bone marrow are important to distinguish essential thrombocythemia
      from early, prefibrotic stages of primary myelofibrosis, which frequently exhibit
      elevated platelet levels. The specific histological bone marrow patterns of the
      diseases were outlined in the fourth version of the WHO classification; however,
      several investigators have claimed that the criteria exhibit poor interobserver
      reproducibility and are not sufficiently robust to discriminate essential
      thrombocythemia and early-stage primary myelofibrosis. This review highlights the
      recent debates on the role of bone marrow histopathology in essential
      thrombocythemia.

PMID- 22880234
TI  - [Overview of lymphoid neoplasms in the fourth edition of the WHO classification].
AB  - The fourth edition of the "WHO Classification of Tumours of Haematopoietic and
      Lymphoid tissues" was published in 2008 as an updated version of the third
      edition published in 2001. In this review, the revised points in the lymphoid
      neoplasms in the fourth edition were summarized from the viewpoint of doctors and
      medical technologists in clinical laboratories in hospitals. The diseases are
      classified based on information about morphology, immunophenotype, genetic
      features, and clinical features. B lymphoblastic leukemia/lymphoma with 7
      recurrent genetic abnormalities is individually classified as a provisional
      entity. Anaplastic large cell lymphoma is divided into two entities, ALK positive
      and ALK-negative. The pathogenesis of the former is involved with ALK gene
      rearrangement with several partner genes. Two borderline categories between
      diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, and between DLBCL and
      classical Hodgkin lymphoma are newly recognized as a distinct disease entity
      based on the overlapping morphological and genetic features. In the diagnosis of
      lymphoid neoplasms, understanding the morphological features is fundamental. On
      the other hand, the importance of immunohistochemistry and flow cytometry to
      clarify the immunophenotype, and chromosomal analysis and genetic examination to
      clarify the genetic features has been raised.

PMID- 22880235
TI  - [Certifying examination which college of laboratory medicine of Japan is
      sponsoring].
AB  - Becoming a Medical Technologist capable of contributing to the clinical field
      requires an ability to keep up with rapid advances in the field of medicine, as
      well as the diligence to constantly keep abreast of new discoveries and
      technologies. To this end, one should forge a social identity as a Medical
      Technologist, thereby bringing more esteem to the profession. Moreover, applying
      knowledge of medical laboratory work to not only medicine but also other fields
      is linked with maintaining and improving public health, which is an important
      objective for the Medical Technologist. In society, the various certifications
      held by such Medical Technologists are acquired as part of a lifelong learning
      process and not only lead to individual advancement but also, presumably,
      business expansion through the application of prodigious knowledge and skills.

PMID- 22880236
TI  - [Certification system for technological professionals towards standardization of
      molecular-genetic testing].
AB  - The College of Laboratory Medicine of Japan, in collaboration with the Japanese
      Society of Laboratory Medicine, has developed a certification examination for
      technological professionals for the purpose of nurturing professionals possessing
      a high level of competency in the field of molecular analysis or molecular
      genetic testing, and thus providing the quality health care services.
      Certification levels are separated into two levels: molecular analysis
      technologist and specialist. The former measures basic knowledge and skills. The
      latter measures the competencies defined in the statement, which includes
      compliance with the standards or guidelines for quality assurance of molecular
      genetic testing. The former began in 2007, and 398 professionals have been
      certified in 5 years. The latter is beginning in 2012. Personnel qualification
      linked with the standards is expected to be an efficient and effective approach
      to providing the quality service.

PMID- 22880237
TI  - [Current state and the future of medical technologist as a specialist Japanese
      Association of Medical Technologists].
AB  - The recognition mechanism is composed of seven groups that conduct qualifying
      examinations within each region. The average pass rate in three qualifying
      examination areas conducted by JAMT is 77.2%. It is necessary to integrate
      similar qualifying examinations in the future and the new "Integrated management
      technologist system" has a key role from the aspect of personnel training.
      Requirements for the integrated management inspection technologist are as
      follows: 1) Person who obtains many positive evaluations; 2) Excellent
      personality; 3) Person with a sense of justice; 4) Person with resolution-making
      abilities and decision; 5) Person who can see the heart of an issue; 6) Person
      who has the potential to become a leader; 7) Person with crisis-management
      ability. Also, selected personnel are expected to become leaders not only in
      their field of expertise but also within their hospital and JAMT management.

PMID- 22880238
TI  - [Present situation and future prospects of the certification system for medical
      technologists--from the viewpoint of the Japanese Society of Clinical Cytology].
AB  - The circumstances surrounding the certification examination for cytotechnologists
      in Japan are closely related with the history of the Japanese Society of Clinical
      Cytology. The examination for cytotechnologists is open only to medical
      technologists. The examination has two parts: primary and secondary.
      Qualification for candidacy for the secondary examination requires candidates to
      have passed the primary examination. The rate of successful applicants in the
      past 10 years was approximately 25-40%. Certified cytotechnologists are required
      to renew their qualifications every 4 years for their study and job history. I
      will present the purpose of the qualification update system, future themes, the
      reporting system for cytodiagnosis, and the possibility that the certification
      examination for cytotechnologists will become a national examination.

PMID- 22880239
TI  - [The national institutes of public health in the contemporary world].
AB  - The article analyses the modern international experience of organization and
      functioning of medical research institutions known as the national institutes of
      public health. The role of these institutes in the development of health policy
      and reforms is exemplified on such countries as Hungary, Great Britain. USA, Peru
      and Japan. It is demonstrated that the national institutes of public health are
      involved into research of the key issues of population health and health care. In
      certain countries these institutions are combined into the National network of
      public health institutes. The actuality and need for such kind of institutions in
      Russia is demonstrated.

PMID- 22880240
TI  - [The regional characteristics, trends and factors of development of health care
      in Smolenskaya oblast].
AB  - The article analyses the characteristics of municipal public health, which
      implements the major part of everyday support of public guarantees of medical
      care free-of charge. The regional characteristics of population structure in
      Smolenskaya oblast are analyzed The impact of population health conditions on the
      public health system of oblast is established. It is proved that the formation of
      regional health system is impossible without analyzing the demographic situation
      in the region and its trends.

PMID- 22880241
TI  - [The morbidity and mortality of malignant neoplasms in Russia and certain foreign
      countries].
AB  - The article presents data to testify that despite the complicacy of resolving the
      problem of decreasing malignant neoplasms mortality the total mortality due to
      this pathology is lower in the European developed countries than in Russia.
      Besides, the detectability of this pathology is much higher in European region.
      This paradox situation should be known to national health authorities. To
      decrease the malignant neoplasms mortality of Russian population therefore to
      reduce inequity in health the changes within the whole public health system are
      needed.

PMID- 22880242
TI  - [The epidemiologic evaluation of oncologic situation in Sverdlovskaya oblast].
AB  - The article deals with the issues of effectiveness of oncologic medical care in
      towns and cities of Sverdlovskaya oblast. The high effectiveness of functioning
      of the ambulatory oncologic department in the structure of polyclinic is
      demonstrated.

PMID- 22880243
TI  - [The characteristics of formation of primary disability of adult population of
      Nijegorodskaya oblast].
AB  - The article deals with patterns of formation of primary, disability of adult
      population of Nijegorodskaya oblast. The analysis was applied to study in
      Nijegorodskava oblast the dynamics of'primary and general morbidity temporary
      disability, primary disability and adult population mortality from 2000 to 2009.
      The degree of interrelationship between the main health indicators of population
      of Nijegorodskaya oblast was estimated. It was proved mathematically that the
      disability is mainly not a medical but social occurrence. The process of
      formation of disability is mainly impacted not by morbidity but by other factors
      such as accessibility and quality of medical, medical social, expertise care, law
      making in social policy, etc.

PMID- 22880244
TI  - [The trends in changing of major causes of death of population of Novgorodskaya
      oblast].
AB  - The analysis of the indicators of common causes' mortality in Novgorodskaya
      oblast during the first decade of XXI century is presented. The differences in
      the levels of mortality as compared with mortality rates in the Russian
      Federation and North-West Federal okrug are discussed. Since 2004, the consistent
      trend of mortality decrease and life span increase has been established. Despite
      this tendency, the level of mortality is still high. It is underlined that a
      significant decrease of both total mortality and common causes mortality can be
      achieved first of all in the result of alterations in human behavior

PMID- 22880245
TI  - [The medical social characteristics of women of active reproductive age and their
      families].
AB  - The article presents the comparative medical social characteristics
      ofreproductive attitudes and reproductive behavior of urban families in present
      conditions. The risk factors leading to small number of children in families of
      various types are analyzed. The health characteristics of'women with one, two,
      three and more children are presented.

PMID- 22880246
TI  - [The evaluation of health of medical personnel of ambulance care and impacting
      factors].
AB  - The analysis of self-assessment of medical personnel of ambulance care revealed
      that 13.2% of respondents consider themselves as healthy persons, 35.1%--as
      practically healthy, 39.2%--as rarely being ill, 12%--as often being ill
      According to the poll data, deterioration of health is promoted by such personal
      factors as disregard of one's health (35%) and chronic diseases (25.3%). Its own
      role play such external factors as professional characteristics (34%). ecological
      conditions (23%), poor conditions of work (22.2%). The amelioration of health is
      supported mainly by sport exercises (42.8%). The significant role in this process
      play the improvement of work conditions, the enhancement of quality of medical
      examninations and the introduction of professional dispanserization.

PMID- 22880247
TI  - [The structural functional analysis of activity of emergency care service of the
      Russian Federation].
AB  - The article presents the results of structural functional analysis of official
      statistic data activity of emergency care service of the Russian Federation. It
      is demonstrated in dynamics its resource support, structure of causes of
      emergency calls and hospitalizations, main volumes of work and most acute
      problems. The research data demonstrates the need of further development of
      service ideology, its material technical support, optimization of strength and
      structure of emergency care units and manpower resource support.

PMID- 22880248
TI  - [The reserves for development of counseling diagnostic care in public health
      system].
AB  - The article analyses the social aspects and reserves for development of
      counseling diagnostic care in public health system exemplified by the state
      Novosibirsk oblast clinical diagnostic center. The ultimate result of the
      ocganization of system of diagnostic centers is to establish conditions for
      early, including preclinical diagnostic of wide-spread social hazardous diseases,
      in particular those which result in early disability of population. Yet another
      result is an effective overcoming of deficiency of qualitative highly informative
      counseling diagnostic care on the level of national public health systemn. It is
      demonstrated that the modernization within the framework of profitable activities
      is one of the most significant organizational technological reserves to increase
      the accessibility, timeliness and effectiveness of counseling diagnostic care
      (exemplified by oncologic pathology) and to optimize functionimg of regional
      counseling diagnostic centers. The results of analysis of patients' sociologic
      survey objectively testify the positive dynamics in patients' satisfaction of
      medical care.

PMID- 22880249
TI  - [On the issues of functioning of the clinic of research institute of balneology].
AB  - The article presents the results of analysis of effectiveness of application of
      main resources in organizing and quality supporting of medical diagnostic care to
      patients in the clinic of research institute of balneology profile. The result
      data points out the insufficient effectiveness of application of these resources;
      the defects in organization and quality of curative diagnostic and rehabilitation
      care. They determine the priority directions of enhancement of functioning of the
      institution being a clinical base of research institute of balneology.

PMID- 22880250
TI  - [The analysis of social satisfaction of population with ambulatory polyclinic
      care].
AB  - The article deals with analysis of social satisfaction of patients with
      ambulatory polyclinic care. The study of satisfaction was organized using the
      technique of risk factors assessment. It is established that the conditions of
      medical care provision in polyclinic are the risk factors impacting the total
      satisfaction of patients with medical care. The degree of patients' satisfaction
      is determined The absence of influence of medical services payments on the level
      of patients' satisfaction is revealed.

PMID- 22880251
TI  - [The assessment of physicians of quality of physiatrics in the in-patient
      hospital department].
AB  - The article discusses the results of sociological survey of physicians of
      departmental hospital concerning the issues of quality of physiatrics treatment
      and its impacting factors.

PMID- 22880252
TI  - [On the issue of the role of medical education in formation of public health
      professional].
AB  - The article presents the results of surveys of students of the Tver medical
      college (N=227) and physicians of different specialties (N=400). It is
      established that some students enter the medical college without having a calling
      for the profession and does not plan to precede working in medicine field.
      According the data, about 28% of students the wish to become a physician
      decreased during education in the college. Among physicians, only 55% are
      satisfied with the quality of their professional education in the university.
      They are not receiving the needed information concerning the official documents
      regulating their activities. It is needed to enhance the system of students'
      selection to enter the medical universities, to increase the quality of medical
      education and to develop the system of measures motivating medical professionals
      to work in their profession field.

PMID- 22880253
TI  - [From the international experience of implementing the public-private partnership
      in modern public health system].
AB  - The article analyses the issues of implementation of public-private partnership
      in public health system of certain countries. On the example of long-term
      international project EUROPEAID the basic criteria and characteristics of such
      partnership are demonstrated The priority areas for public-private partnership
      are established (AIDS prevention, reproductive health, tuberculosis, etc.). The
      conditions determining the effectiveness of public-private partnership in the
      medical care system are established The organizational and legal approaches to
      enhance the implementation of are established in public health of Russia are
      proposed.

PMID- 22880254
TI  - [The practical medicine and its reformation in XVII-XIX centuries. Report 1: the
      classification medicine. The origin of clinical idea].
AB  - The article considers the key positions of curative diagnostic concept of Galenus
      and the causes of denial of its application in medical practice in the middle of
      century. The two main directions of reforming the practical medicine during the
      first scientific revolution are demonstrated. The basic foundations of the
      curative diagnostic concept of classification medicine and the results of its
      implementation are discussed The origin of innovative methodological approach to
      the studying of issues of practical medicine is described The gradual formation
      of a new style of physician mentation (clinical mentation) and becoming of
      clinical medicine are analyzed.

PMID- 22880255
TI  - [The issue of medical care accessibility in pre-revolutionary Russia].
AB  - In pre-revolutionary Russia, the issue of medical care accessibility considered
      concerning the population groups with lower incomes. Later the notion of
      accessible medical care evolved. It was formulated in a most capacious way by
      Zemstvo medicine. The zemstvo physicians inputted into this notion not only the
      availability of curative institutions and medical personnel, but also a
      territorial and economic accessibility including the provision of population with
      specialized medical care. The concept proposed by zemstvo public figures was
      approved by the medical community and public authorities.

PMID- 22880256
TI  - [The correspondence trials as a form of qualifying evaluation of pharmaceutists
      in Russia of the first half of XIX century].
AB  - The article describes the qualifying evaluation of pharmnaceutists in Russian
      universities introduced by the charters instituted in the first half of XIX
      century. The significance of well-established rules of full-time and
      correspondence trials of applicants for pharmaceutical degrees is considered The
      merits and shortcomings of correspondence form of qualification trials
      implementation are indicated.

PMID- 22880257
TI  - [The medical service of Leningrad front during the Leningrad blockade].
AB  - The article presents the activities of the medical service of Leningrad front
      during the Leningrad blockade. The conditions and characteristics of treatment
      evacuation, sanitary hygienic and anti-epidemic support of military forces during
      this historical period are analyzed

PMID- 22880258
TI  - Lyme borreliosis--epidemiological analysis of incidence in the northern region of
      Slovakia.
AB  - Lyme borreliosis is a contemporary public health problem. That's why we devoted
      our prospective and retrospective epidemiological study to the incidence of
      anthropozoonosis in the regions of Liptovsky Mikulas and Ruzomberok. We created a
      group of 476 patients from the medical documentation of infectious units. These
      patients were treated for Lyme borreliosis from 1989 to 2010, 280 patients in the
      county of Liptovsky Mikulas, and 196 patients in the county of Ruzomberok.
      Morbidity in different years was compared to national data. The number of ill
      patients (n = 476) compared to data about reported cases from The Regional Public
      Health Office in Liptovsky Mikulas (n = 221) confirmed the lack of a warning
      service. The actual incidence of Lyme disease in the Liptov region is twice
      higher. The average morbidity was 16.24 people per 100,000 of the population for
      the last 22 years. The highest morbidity from 476 treated patients (men 37.52%,
      women 62.48%) was in the group aged from 45 to 54 years with an average annual
      morbidity 21.18/100,000. The study also confirmed the higher incidence of Lyme
      disease in the female population.

PMID- 22880259
TI  - [Microneutralization assay in the diagnosis of influenza infection].
AB  - Serology plays an important role in the diagnosis of influenza, particularly in
      the detection of post-vaccination and post-infection antibodies. When considering
      the range of diagnostic options, the serological method should be selected
      depending on the circumstances - whether single or paired serum samples are
      tested, whether adequate patient medical history data are available, whether
      epidemiological links are suspected, and, in particular, to what purpose the
      result will be used (differential diagnosis, post-infection follow-up, post
      vaccination monitoring, etc.). The virus neutralization assay is one of the most
      sensitive and most objective serological tests, but it is highly dependent on the
      reaction balance and quality of the virus used. Determining the protective titer
      is crucial for the routine practice. Based on our experiments, we concluded that
      the virus neutralizing antibody titers are up to eight times as high in
      comparison with the hemaglutination inhibition test (HIT) or complement fixation
      reaction (CFR), but the correlation varies and is significantly influenced by
      interindividual variation in anti-neuraminidase antibodies and those against some
      internal proteins of influenza virus. We assume that the protective titer in the
      virus neutralization assay will be not less than 1:80. The predictive value of
      the titers below 1:40 is questionable.

PMID- 22880260
TI  - [Outbreaks of viral hepatitis E in the Czech Republic?].
AB  - Until recently, viral hepatitis E (VHE) has typically been an imported infection,
      related to travel to developing countries. A number of travel-unrelated VHE cases
      currently diagnosed in the Czech Republic. Outcomes of the epidemiological
      investigations of two VHE outbreaks associated with the consumption of pork and
      pork products at pig-slaughtering feasts are presented. Thirteen cases have been
      reported in the first outbreak and eight cases in the second outbreak. The
      epidemiological investigations are described and the experience gained in
      analysing suspected biological specimens is presented. The source of infection
      has not been identified in the first outbreak while in the other one, a link
      between human cases and infection in farm pigs was revealed for the first time.
      Although the epidemiological investigation may not always lead to the detection
      of the VHE source, it must be conducted in any outbreak and can only be
      successful when done in cooperation of the public health authorities with the
      veterinary health agency.

PMID- 22880261
TI  - [The comparison of selected virulence factors in Pseudomonas aeruginosa catheter
      isolates].
AB  - Healthcare quality improvement brings about an increasing number of invasive
      diagnostic and therapeutic procedures and thus also an increasing number of high
      risk patients prone to hospital infections. Pseudomonas aeruginosa is one of the
      most commonly isolated nosocomial species and the treatment of the infection is
      often long and problematic, with frequent recurrences. The pathogenesis of
      Pseudomonas infection is associated with a range of virulence factors. In the
      present study, 93 catheter isolates of Pseudomonas aeruginosa were screened for
      the biofilm formation, motility and secretion of selected extracellular products.
      A high rate of the strains tested were producers of hemolysins, LasB elastase,
      and pyoverdines (> 70%). The biofilm formation was detected in 80% of isolates
      and formation of aerated biofilm was present in 90% of isolates with a positive
      correlation found between the two types of biofilm formation (p = 0.00583; gamma
      = 0.551). All strains showed swarming motility, 95% of strains showed swimming
      motility, and 75% of strains showed twitching motility. Among the virulence
      factors studied, only pyocyanin and pyochelin were produced by a lower proportion
      of isolates (< 25%). A positive correlation was seen between the production of
      some extracellular molecules (pyochelin and pyocyanin, pyocyanin and LasB
      elastase, and LasB elastase and haemolysins), between biofilm formation and
      formation of aerated biofilm, and between formation of aerated biofilm and
      pigments (pyoverdine and pyocyanin) production. On the other hand, a negative
      correlation was found between biofilm production and LasB elastase production and
      between the production of biofilm under immersion and pigments (pyoverdine and
      pyocyanin) production. All correlations are significant at the level p = 0.05,
      with the correlation coefficient gamma > 0.50.

PMID- 22880262
TI  - [30 years since the first AIDS cases were reported: history and the present. Part
      I].
AB  - The 30-year natural history of AIDS disease is presented from the first clinical
      cases reported in 1981 to the identification of the HIV as the etiological agent
      of the disease. The priority dispute between Robert C. Gallo and Luc Montagnier
      over the discovery of the human immunodeficiency virus is briefly addressed. The
      final confirmation of the French priority was provided by the fact that the Nobel
      Prize in Medicine 2008 was awarded to Luc Montagnier and Francoise Barre-
      Sinoussi from the Pasteur Institute in Paris.

PMID- 22880264
TI  - [Concept of the discipline of epidemiology (2012)].

PMID- 22880265
TI  - [The future of trauma surgery at CR].

PMID- 22880266
TI  - [GIST: current knowledge and treatment modalities].
AB  - GISTs represent a specific group of mesenchymal tumors with unpredictable
      biological features. Approximately 30% of newly diagnosed GIST tumors are
      malignant or have a high potential for malignancy. Currently, GISTs are routinely
      identified using histological, immunohistochemical, and molecular genetic assays.
      However, clinical diagnosis, particularly of small or intramural GISTs, might be
      difficult. Endoscopic examinations and fused PET/CT imaging are the most useful
      techniques for imaging and monitoring the disease progression. Surgical treatment
      is the first-line treatment and the only method that might lead to full remission
      in patients with primary GISTs. At the present time, there is no consensus on the
      issues whether to perform resections in patients with positive margins and
      resections of metastases. Biological therapy with imatinib mesylate is
      recommended in patients with newly diagnosed, locally advanced, inoperable, or
      metastasizing gastrointestinal GISTs that express the c-KIT protein. Treatment
      may reduce a primary tumor to a size small enough for surgical excision. Current
      research is focused on the development of new therapies for the treatment of
      advanced disease and/or disease prophylaxis.

PMID- 22880267
TI  - [Quality of life is an important factor in the indication in patients with
      advanced pancreatic carcinoma--a prospective multicentric study].
AB  - INTRODUCTION: The aim of this report is to present results of prospective
      multicentric study on quality of life (QoL) in advanced ductal pancreatic
      adenocarcinoma patients. MATERIAL AND METHOD: In 426 patients with advanced
      ductal pancreatic adenocarcinoma, the following parameters were studied: type of
      treatment, complication rates, 1, 2 and 3-year survival rates. QoL was assessed
      in 151 patients, using a generic SF-36 questionnaire prior the therapy and then 3
      months after the treatment. Arithmetic mean and standard deviation (SD) were used
      for the QoL pool analysis. The results were evaluated using SF-36 software, t
      test for independent samples, ANOVA, paired t-test and SPSS 19.0.1 (IBM
      Corporation, 2010). The p value < 0.05 was considered as statistically
      significant. RESULTS: There was a significant difference in the median, 1,2 and 3
      year survival rates in the patients with stage III pancreatic cancer who
      underwent radical resection (RR) compared to the paliative therapy patients (p <
      0.001). The highest initial overal QoL value was observed in 39 stage III
      patients who underwent RR (60.5 +/- 1.84) and no significant decrease in this
      value was recorded over a 3-month postoperative period (difference--5.1 +/- 16.6,
      p = 0.064). Paliative therapy resulted in significant reduction in the overall
      QoL value (p = 0.020). In the paliative therapy group of patients, BDA resulted
      in significant reduction in the overall QoL value 3 months after the procedure (p
      = 0.017 vs. ns.). In the group of stage IV patients, nonsignificant increase in
      the overall QoL value was recorded in 8 patients 3 months after BDA (46.4 +/-
      17.0 vs. 51.1 +/- 9.5 p = 0.525). Nonsignificant increase in the overal QoL
      values was also observed in 18 patients after stent introduction (30.6 +/- 8.3
      vs. 31.5 +/- 8.5 p = 0.783). Nonsignificant deterioration in QoL was recorded in
      patients undergoing exploration, whose initial QoL values corresponded with those
      in RR patients, while 3 months after the explorative surgery their QoL values
      were similar to those recorded in the stent group patients (62.0 +/- 16.1 vs.
      41.7 +/- 23.6 s rozdilem -20.3 +/- 16.2 p < 0.001). CONCLUSION: Based on the
      results of the multicentric prospective study in patients with locally advanced
      stage III and IV ductal pancreatic adenocarcinoma, the following conclusions can
      be presented: (1) median and 1, 2 and 3-year survival rates in stage III patients
      were significantly higher in the RR group compared to the paliative therapy
      patients, (2) initial QoL in stage III patients was significantly the highest in
      patients who underwent RR. Significant decrease in QoL was recorded in BDA
      patients. Paliative stent introduction resulted in nonsignificant improvement in
      the QoL 3 months after the procedure, while the initial QoL values were the
      lowest in this group, (3) QoL assessment in stage IV patients showed
      statistically nonsignificant improvement after BDA or stent procedures, the most
      significant deterioration was observed in the exploration group, (4) no
      complication which would result in prolongation of the respective hospitalization
      times was recorded in 67%, (5) early postoperative complications did not result
      in significant QoL deterioration 3 months after the procedure, (6) absence of
      chemotherapy results in significant decrease in QoL.

PMID- 22880268
TI  - [Biomarkers in the detection of minimal systemic dissemination in lung cancer
      patients].
AB  - INTRODUCTION: Minimal systemic disease (MSD) means the presence of circulating or
      disseminated tumour cells in mesenchymal compartments of a patientts' body
      (lymphatic nodes, blood or bone marrow). The aim of our pilot study was to
      identify sensitive and specific markers for MSD detection in 50 lung cancer
      patients, who underwent curative surgery in the I. Department of Surgery, Faculty
      of Medicine and Dentistry, Palacky University and Faculty Hospital Olomouc in
      2009 and 2010. MATERIAL AND METHODS: Absolute gene expression of carcinoembryonic
      antigen (CEA), epidermal growth factor receptor (EGFR1), lung-specific X protein
      (LUNX) and hepatocyte growth factor receptor (c-met) was determined in peripheral
      blood, bone marrow and pulmonary blood of 50 lung cancer patients using real-time
      reverse transcriptase-polymerase chain reaction (real-time RT-PCR). RESULTS: (1)
      The LUNX marker is specific and sensitive for MSD detection in lung cancer
      patients. (2) The CEA positivity for MSD in the bone marrow correlated
      significantly with histopathological grading (GI-GIII). (3) Higher expression of
      CEA and c-met was found in pulmonary blood of patients with hilar or mediastinal
      lymphadenopathy. (4) Higher expression of MSD markers (CEA in bone marrow, c-met
      in peripheral blood and LUNX in pulmonary blood) correlated with higher pTNM
      classification. CONCLUSION: Minimal systemic disease detection in lung cancer
      patients is technically feasible using sufficiently sensitive and specific
      markers for RT-PCR. Minimal systemic disease detection can be used to guide
      further systemic treatment. This theory must be validated in a larger group of
      patients and correlated with clinical data, especially with survival data.

PMID- 22880269
TI  - [Prevention of parastomal hernia using laparoscopic introduction of a prosthetic
      mesh--initial experience].
AB  - INTRODUCTION: Parastomal hernia is a very common complication after stoma
      formation. Current surgical procedures for repairing parastomal hernia have
      unsatisfactory results. The aim of this study was to evaluate our initial
      experience with laparoscopic prophylactic mesh placement at the time of stoma
      formation. MATERIAL AND METHODS: Four patients underwent laparoscopic
      abdominoperineal rectal cancer resection with prophylactic parastomal mesh
      placement. A specially designed mesh made of polyvinylidene fluoride with central
      funnel (Dynamesh IPST) was implanted using an intraperitoneal onlay technique.
      The surgical data, the frequency of mesh-related complications as well as the
      rate of parastomal henias were evaluated. RESULTS: The mean operating time for
      mesh placement was 15 min (10-25 min.). No mesh- related complications or
      infection was observed and no parastomal hernia could be detected clinically. To
      this date, the mean follow up time has been six months (4-8 months). CONCLUSION:
      Laparoscopic prophylactic parastomal mesh placement might be a safe and effective
      procedure with a potential to reduce the risk of parastomal hernia, at least in
      the short run. However, our experience is limited due to the small number of
      patients included in the study. Additional large trials with long term follow up
      are necessary.

PMID- 22880270
TI  - [Prognostic clinical factors in colorectal cancer after radical therapy].
AB  - INTRODUCTION: Colorectal anastomoses frequently become the site of of
      complications after surgical procedures for colorectal cancer. Anastomotic
      dehiscence has a significant impact on the whole p postoperative disease course,
      may influence the overal survival (OS) and disease free interval (DFI). The aim
      of our study was to analyze clinical and histopathological factors, that could
      facilitate detection of dehiscences and are related to the prognosis of patients.
      MATERIAL AND METHODS: The authors performed statistical analysis of a cohort of
      patients (340 pacients, 207 males, 133 females) who underwent radical resection
      followed by anastomosis on the large intestine during 2003-2007. The following
      factors were assessed: age, gender, staging, protective stoma, neoadjuvant
      chemotherapy, neoadjuvant radiotherapy, adjuvant chemotherapy, adjuvant
      radiotherapy and anastomotic insufficiency. Complications were evaluated
      according to Clavien and Dindo classification. RESULTS: The analysis confirmed
      the following factors to be statistically significant for prognosis of OS and
      DFI: In stage T4 subjects, the risk of death was 2.5 x higher and the risk of
      recurrence was 1.9 x higher than in the lower disease stage subjects. The
      presence of N2 lymph node metastases increases the risk of death 3.7 x and the
      risk of recurrence 3.6 x, compared to N0 and N1 cases. The presence of
      postoperative complications classified asf III.-V. grade according to Clavien and
      Dindo classification increases the risk of death 4x. The risk of death was 5.5 x
      higher in patients with dehiscence of anastomosis. The surprising finding was
      that even protective stoma increases the risk of death 5.4 x. Patients who did
      not undergo adjuvant chemotherapy were at 2 x higher risk of death. In patients
      with IIIA, IIIB, IV, V complications, the following factors proved to be
      statistically significant for prognosis of OS: leakage, protective stoma,
      adjuvant chemotherapy and adjuvant oncological treatment. In patients with
      complications I and II, the following factors were proved to be statistically
      significant for prognosis of OS: staging and lymph nodes metastases. Multivariate
      analysis CART confirmed significant correlation between the lymph nodes
      positivity and the Clavien and Dindo classification of complications. CONCLUSION:
      Analysis of clinical and histopathological factors is important for prediction of
      prognosis in patients with colorectal cancer after radical surgical treatment.
      Detection and application of these prognostic factors in postoperative period
      could influence the strategy of treatment and thus the overal survival in
      patients with radical resections for colorectal carcinoma. Nonadministration of
      adjutant chemotherapy results in a significant decrease in OS and DFI.

PMID- 22880271
TI  - [Laparoscopic adrenalectomy--indications and selection criteria].
AB  - INTRODUCTION: Laparoscopic adrenalectomy has become a standard surgical procedure
      for the most of adrenal gland disorders. Hormonal active adenomas,
      feochromocytomas even some malignant tumors are the most frequent indications.
      The number of operations for accidentally diagnosed foci has grown rapidly. It
      has been suggested to revise recommendations specifying criteria, based on which
      incidentaloma is indicated for adrenalectomy. The aim of this work is to compare
      the results of adrenalectomies for hormonal active lesions and incidentalomas.
      MATERIAL AND METHODS: An analysis of 65 patients who underwent adrenalectomy in
      the Department of Surgery University Hospital Brno Bohunice from 2005 to 2010.
      Correlation between preoperative examination outcomes and postoperative histology
      findings was performed. Furthermore, findings in patients indicated for surgery
      for hormonally active versus for hormonally inactive suprarenal tumors were
      compared. RESULTS: Thirty-eight patients underwent laparoscopic surgery for
      hormonally active adrenal tumors, one for bilateral metastasses of bronchogenic
      carcinoma. In 26 cases adrenalectomy was indicated for incidentaloma. Adrenal
      hyperplasia was the commonest histological finding in the group with hormonally
      inactive tumors. No carcinoma was detected in this group. In 5 of 19 patients
      operated for suspective feochromocytoma, the procedure did not result in blood
      pressure adjustment and feochromocytoma was histologically confirmed in 11 out of
      the 19 subjects. The size of the tumors was significantly higher in
      incidentalomas, compared to hormonally active pathologies. No incidentaloma and
      hypertension subjects experienced alteration in their clinical condition after
      the procedure. CONCLUSION: Laparoscopic adrenalectomy is a standard procedure in
      the majority of hormonally active focal suprarenal conditions. Patients with
      accidentally detected suprarenal tumors should be carefully indicated, taking
      into consideration internal comorbidities and any surgical procedures in a
      patient's history. The benefit of adrenalectomy for the clinical condition
      alteration is arguable in incidentalomas. The National Institutes of Health
      U.S.A. (NIH) consensus guidlines should be strictly followed during the decision
      making proces. Indication for adrenalectomy in tumors of less than 6 cm and with
      benign appearance on CT or MRI is not considered rational.

PMID- 22880272
TI  - [Retroperitoneoscopic adrenalectomy with dorsal approach].
AB  - INTRODUSTION: Various surgical mininvasive approaches for adrenalectomy have been
      established over the last two decades. We are evaluating the retroperitoneoscopic
      adrenalectomy with dorsal approach. MATERIAL AND METHODS: The prospective open
      clinical trial was carried out to evaluate intra-operative (operations time,
      intraoperative complications, blood loss, conversion rate) and peri-operative
      parameters (morbidity, mortality, hospital stay). Patients who underwent
      retroperitoneoscopic adrenalectomy with dorsal approach were included in the
      trial. A tumor size above 12 cm or BMI higher than 35 kg/m2 were considered
      asexclusion criteria. All the patients were perioperatively managed by a
      multidisciplinary team. RESULTS: A total of 81 patients were assessed (average
      age: 45.7 yrs, 37 males, 44 females, BMI 27.8 kg/m2). The average operating time
      was 61 minutes. The intraoperative blood loss was below 20 ml. The mean hospital
      stay was 2.1 days. Morbidity was 2.7% and mortality 0%. CONCLUSION:
      Retroperitoneoscopic adrenalectomy with dorsal approach is considered a method of
      choice in our hospital. The use of this approach is safe, efficient, with
      excellent reproducible operative results and impressive patient recovery.

PMID- 22880273
TI  - [Extragastrointestinal stromal tumor (EGIST)--a case review].
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract. Due to the presence of thyrosine kinase receptors within
      the tumor tissue, GIST is thought to originate from gastrointestinal pacemaker
      cells, the intersticial cells of Cajal. Tumors with the same morphological and
      imunohistochemical characteristics detected outside the gastrointestinal tract,
      are called extragastrointestinal stromal tumors (EGIST). Biological
      characteristics of these tumors is uncertain and the malignancy rates are
      difficult to predict. Surgical R0 resection in resecable tumors is the only
      option with the potential for complete cure. Nevertheless, the recurrence rates
      are high. Adjuvant biological treatment with imatinib, a thyrosine kinase
      inhibitor, reduces the risk of relapses. Imatinib administration is also the
      principal treatment method in metastatic GIST disorders. The article offers a
      short and complex overview of gastrointestinal stromal tumor (GIST) problematics
      and presents a case report of a patient suffering from EGIST of mesocolon
      transversum treated by R0 resection which was performed under multidisciplinary
      cooperation, with a specialist follow up.

PMID- 22880274
TI  - [McKittrick-Wheelock syndrome: complication of rectal mucinous adenoma].
AB  - The McKittrick-Wheelock syndrome is a very rare complication of rectal villous
      adenoma, characterized by fluid and electrolyte hypersecretion from a rectal
      tumour, which can lead to acute renal failure. We present a case review of a 67
      year-old male patient hospitalised for profuse secretory diarrhea, with
      electrolyte dysbalance and progressive renal failure. A rectoscopic finding of
      massive rectal adenoma contributed to establishing the correct diagnosis.
      Resection of the affected part of the rectum resulted in rapid restoration from
      mineral imbalance and improvement of renal functions. The reported case shows the
      necessity of interdisciplinar management and the importance of surgical treatment
      in patients with this rare diagnosis.

PMID- 22880275
TI  - [Prevention of TEN in surgery, prolonged thromboprophylaxis].
AB  - Deep vein thrombosis (DVT) and its consequences are the most frequent cause of
      morbidity and mortality in operated patients, in whom the risk factors for its
      onset are accumulated. In general surgery, its occurrence was confirmed in 10-40%
      of operated patients with no prophylaxis, while after major orthopaedic
      procedures, the rate was up to 60% of patients. Prophylaxis is a fundamental
      element of the whole strategy of all active measures in prevention of
      thromboembolic complications. The authors present current methodology of TEN
      prophylaxis, including a long-term administration, which is accepted by most
      countries and expert societies, across all branches of surgery.

PMID- 22880276
TI  - [Developments in pancreatic surgery at the 1st Surgical Department 1st Faculty of
      Medicine, Charles University and General University Hospital in Prague].
AB  - INTRODUCTION: Surgical treatment of pancreatic diseases has been going through
      certain changes and developments. This article aims to describe the changes in
      diagnosis and treatment that have occurred over the years. MATERIAL AND METHODS:
      Groups of patients from three different periods (1954-1999, 2002-2006 and 2007
      2011), all of them having undergone elective follow-up for the diagnosis of acute
      or chronic pancreatitis (AP, CHP), pancreas and papilla tumours, terminal
      choledochus, and other less common tumours in this region, are described.
      Monitoring has focused on the indication criteria, the extent and method of the
      surgical procedure, perioperative lethality and morbidity, including
      complications, and also survival rate. RESULTS: In AP patients we recorded a
      significant drop in indications to surgery (38% vs. 16%), a shift in intervention
      time from 8.9 to 22.5 days, a decrease in lethality by 24%, or, as the case may
      be, by 3.5% (yet 7.9% during the first three months). The results show the
      domination of open abdominal procedures and a rising number of non-interventions.
      In CHP patients we detected a 30% increase in the number of resection procedures
      /Whipple/, a slight increase in drainage procedures (by 6%), and a decrease in
      drainage-resection procedures. The overall drop in the number of procedures in
      CHP patients probably relates to endoscopic and miniinvasive treatment. In
      pancreatic tumours we found domination of adenocarcinoma (92.6%), but also an
      increase in the number of cystic and endocrine tumours (2.6% and 4.8%) as a
      result of diagnostics and centralisation of care. We also recorded a decrease in
      exploratory laparotomy cases to 12%. In patients with resectable tumours we
      performed hemipancreatoduodenectomy in 90%, posterior approach in 2%, and
      vascular resection in only 4%. Perioperative lethality stagnates around 2.8%.
      Median survival rate has remained unchanged, as has long-term survival rate.
      CONCLUSION: Although treatment in general has not recorded any revolutionary and
      fundamental benefits, its surgical modality still represents the principal
      treatment and can be considered curative, even in tumours. Pancreatic diseases
      remain to be seen as a multidisciplinary issue and must be approached and dealt
      with as such, optimally in large-volume centres.

PMID- 22880277
TI  - [Outcomes of complex therapy in female patients after breast-saving surgery for
      breast carcinoma at the 1st Surgical Department 1st Faculty of Medicine, Charles
      University and General University Hospital in Prague during a ten-year follow up
      period].
AB  - INTRODUCTION: Good longterm outcomes of complex therapy in operable breast cancer
      can be achieved mainly due to early diagnosis of the tumor, adequate radicality
      of surgery and adequate oncotherapy. The following outcome criteria are
      considered significant: long-term survival rate in complete remission, a number
      of locoregional recurrences and a number of reoperations or mastectomies required
      by results of final histological examination, patient satisfaction with a
      cosmetic result of their breast- saving surgery. Comparison of complex treatment
      results collected from patients who underwent breast-saving procedures performed
      for breast cancer at our department of surgery with data reported in literature.
      MATERIAL AND METHODS: Retrospective analysis of data collected from 106 female
      patients suffering from invasive breast cancer and ductal carcinoma in situ
      operated at our surgery department from 1998 until mid-2002. The sample included
      nine patients who underwent surgery after neoadjuvant oncotherapy. The median
      follow-up time after surgery was 10 years and 7 months. Reresection was indicated
      based on the following criteria, set up by the authors: outline margin of less
      than 1 mm in invasive tumors, and in cases of ductal carcinomas in situ and
      carcinomatous lymphangiopathy their presence directly within the resection line.
      RESULTS: The patient group included 13 (12.3%) patients with early reoperations.
      During the follow up period, locoregional recurrence was recorded in 3 (2.8%)
      patients. A total of 12 (11.3%) patients with generalized breast carcinoma died,
      their median survival was 6 years and 4 months. A total of 90 (84.9%) patients
      are surviving with complete remission of the disease. Thecosmetic outcome was
      evaluated by patients according to a five-point scale. Out of the total of 77
      surviving patients who underwent breast-saving procedures, the authors personally
      contacted 52 subjects (67.5 %). Out of the total, 45 (86.5 %) subjects evaluated
      the cosmetic outcome as excellent or very good. CONCLUSION: The survival rate
      with complete remission and satisfactory cosmetic results is considered to be
      comparable with the data presented in literature. Considering a small number of
      early reresections or mastectomis and locoregional recurrences our clinic
      achieved good outcomes.

PMID- 22880278
TI  - [Pilon fractures of the tibia--a short summary of problems and case reports].
AB  - Fractures of the distal tibia represent serious musculoskeletal injuries. Their
      treatment is rather difficult, requiring highly erudite staff and sufficient
      material equipment. The authors present a group of 41 patients operated on over a
      5-year period and on 4 case reports show their own most frequently used treatment
      options.

PMID- 22880279
TI  - [History of traumatology at the 1st surgical clinic in Prague].

PMID- 22880280
TI  - [A century of progress in the surgical treatment of ileus states].

PMID- 22880281
TI  - [Surgery of esophageal and gastric diseases at the beginning of the 21st
      century].

PMID- 22880282
TI  - [Colorectal carcinoma at the 1st Surgical Clinic in Prague].

PMID- 22880283
TI  - [Functional differentiation along the longitudinal axis of the hippocampus, with
      reference to the neuronal circuits].

PMID- 22880284
TI  - Information-seeking experiences and decision-making roles of Japanese women with
      breast cancer.
AB  - PURPOSE: To investigate the information-seeking experiences and decision-making
      roles of Japanese women with breast cancer, to examine the relationship between
      information-seeking experiences and decision-making roles, and to explore the
      factors that influenced taking a more active role than the preferred role during
      the treatment decision-making process. METHODS: In a cross-sectional study, women
      with breast cancer were retrospectively administered the Control Preferences
      Scale and the Information-Seeking Experience Scale. The Chi-Square test was used
      to compare differences among individual variables in decision-making roles and
      information-seeking experiences. Logistic regression analysis was used to explore
      the factors that influenced taking a more active role than the preferred role.
      RESULTS: One hundred and four patients with breast cancer participated in the
      investigation. Eighty-five patients (78%) perceived themselves as having
      knowledge of breast cancer and most patients (92%) sought information on breast
      cancer. The preferred roles in decision-making that they reported having before
      treatment were 18% active, 69% collaborative and 13% passive. The actual roles
      they perceived having experienced were 27% active, 43% collaborative and 30%
      passive. Although there was concordance of preferred and actual role for only 59%
      of the women, most patients reported that they were satisfied with their decision
      making. Many women with breast cancer reported negative experiences with
      information seeking, including wanting more information (49%), expending a lot of
      effort to obtain the information needed (53%), not having enough time to obtain
      needed information (55%), frustration during the search for information (44%),
      concerns about the quality of the information (45%) and difficulty understanding
      the information received (49%). This study revealed that having a more active
      actual role than the initial preferred role was associated with emotional
      expression to the physician, having undergone mastectomy, and the desire for more
      information. CONCLUSION: Most women with breast cancer sought information on
      breast cancer and expressed a preference for a collaborative relationship with
      physicians in treatment decision-making. Patients who expressed emotion to their
      physician, wanted more information, and underwent mastectomy were most likely to
      change their actual decision-making role toward a more active choice.

PMID- 22880285
TI  - [A hammer, this finger! Mallet finger].

PMID- 22880286
TI  - [Who may (not) ask what?].

PMID- 22880287
TI  - [apoBank has completely left Greece].

PMID- 22880288
TI  - [Many physicians are indifferent about the Web - why that is false].

PMID- 22880289
TI  - [When the fever will not respond].

PMID- 22880290
TI  - [Basal insulin has a "neutral effect" on cardiovascular events].

PMID- 22880291
TI  - ["Very good metabolic control by early insulin administration"].

PMID- 22880292
TI  - [Rapid disease progression, early insulin requirement].

PMID- 22880293
TI  - [Basal insulin and GLP-1 agonist potentiate each other (interview by Dr. med Dirk
      Einecke)].

PMID- 22880294
TI  - [Naturopathy consultation. Pruritus].

PMID- 22880295
TI  - [There is something for intra-auricular treatment].

PMID- 22880296
TI  - [Managing hyperhidrosis].

PMID- 22880297
TI  - [Ten tips for sleeping better].

PMID- 22880298
TI  - [Sleep disorders].

PMID- 22880299
TI  - [Sleep in the elderly].

PMID- 22880300
TI  - [Sleep disorders in major psychiatric diseases].

PMID- 22880301
TI  - [Traumatic finger amputation].

PMID- 22880302
TI  - [Interactions between hypertension, lung diseases and air pollution].

PMID- 22880303
TI  - [Headaches in elderly patients: what is different?].

PMID- 22880304
TI  - [Dual mechanism of action of tapentadol].

PMID- 22880305
TI  - The bond that means so much.

PMID- 22880306
TI  - Neonatal nurse knowledge and skills set in syllabus.

PMID- 22880307
TI  - Why the first two years of life can be make or break.

PMID- 22880308
TI  - Teenagers need advice and support.

PMID- 22880309
TI  - Evolution of a youth work service in hospital.
AB  - Youth workers are based predominantly in the community and use a range of
      informal educational activities to help young people between the ages of 11 and
      25 cultivate their personal and social development. The supraregional paediatric
      nephrology unit at Nottingham City Hospital successfully evaluated the role of a
      youth worker, funded by a national renal charity, and secured long-term funding
      for the post in 2000 (Hilton et al 2004, Watson 2004). This article describes the
      evolution of the youth service over a decade, following the amalgamation of two
      children's units into one site and the creation of a unified youth service for
      the Nottingham Children's Hospital in 2008.

PMID- 22880310
TI  - Developing a nurse-led child sedation service.
AB  - This article explores nurse-led sedation of children in preparation for
      investigations such as magnetic resonance imaging or minor surgical procedures.
      The importance of the multidisciplinary team in setting up, implementing and
      evaluating this new nurse-led initiative is described. Effective planning,
      involvement, agreement and training are key to a successful change in practice,
      with responsibility being delegated to competent nursing staff. Evaluation has
      shown all-round benefits. Trained nurse-led sedation is safe, effective and
      efficient and nurses are motivated to undertake this extended role.

PMID- 22880311
TI  - A paediatric early warning scoring system for a remote rural area.
AB  - Health professionals can fail to identify and treat serious illness or acute
      deterioration in children because of a lack of relevant training, experience or
      supervision. In Argyll and Bute in Scotland a standardised, monitoring system was
      initiated measuring six physiological parameters: temperature, pulse rate,
      respiratory rate, systolic blood pressure, oxygen saturation and consciousness
      level. The total score dictates what actions to take. This local system was
      positively evaluated but a national paediatric early warning scoring system is
      needed.

PMID- 22880312
TI  - An overview of epilepsy in children and young people.
AB  - The role of the nurse is vital in the management of childhood epilepsy. Nurses
      play a key role in supporting the child and the family and ensuring that
      important relevant and accurate information is identified, recorded and reported
      to the team responsible for the medical management.

PMID- 22880313
TI  - [Parent-child attachment and child protection].

PMID- 22880314
TI  - [Marisol Touraine's road map for the future of the public hospital].

PMID- 22880315
TI  - [Prevention of pain in the newborn using heat].

PMID- 22880316
TI  - [Global mortality of premature infants].

PMID- 22880317
TI  - [Improvement and numerous obstacles in pediatric medications].

PMID- 22880318
TI  - [Travel related illness in children].

PMID- 22880319
TI  - [Eighty-year study of birth trends].

PMID- 22880320
TI  - [The European Commission approves the use of adalimumab for children ages 4 to
      12].

PMID- 22880321
TI  - [School phobia. Finding the way back to school].

PMID- 22880322
TI  - [School phobia, definition and symptoms].
AB  - The refusal to go to school has been the subject of studies since the 19th
      century. It is necessary to separate the notions of truancy and school refusal,
      leaving that of anxiety-based school refusal. There exists a link between this
      phenomenon and separation anxiety, a depressive state and family problems.

PMID- 22880323
TI  - [Systemic approach to school phobia].
AB  - School refusal is described in very diverse psychopathological contexts. It
      involves at least two invariables: the child's refusal to go to school and the
      involvement of their family in their difficulties.The systemic description of the
      emergence of this symptom attempts to fix reference points and to offer treatment
      solutions.

PMID- 22880324
TI  - [School phobia in adolescents, treatment and return to school].
AB  - School refusal is a particular entity which involves the school, treatment and
      the family. The therapy is complex and necessarily multimodal. Treatment aims
      towards a rapid return to full-time schooling in the usual environment. It is
      backed up by a psychological support network of caregivers and a sufficiently
      containing and restrictive hospitalisation in a specialised unit.

PMID- 22880325
TI  - [A project-class to rediscover school].
AB  - In 2006 a project-class was created at the medical and pedagogical centre of
      Rennes. This centre takes in, for a 5-week period, students aged between 16 and
      20 suffering from school refusal. The objective, for the young people overseen by
      a tutor, is to once again become a player in their educational project to
      rediscover, in a confidence-building environment, the pleasure of sharing their
      knowledge with their peers.

PMID- 22880326
TI  - [School Phobia Association, support for parents and children].

PMID- 22880327
TI  - [Coming out of isolation is at the heart of school phobia].

PMID- 22880328
TI  - [Transcultural aspects of school phobia].
AB  - It sometimes happens that school is unable to fulfil its vocation as a place of
      integration, both here and elsewhere. Taking Japan as an example, it is possible
      to analyse the cultural components of school refusal in a countrywhere the
      pressure to succeed is so strong. Looking out onto the world helps us to expand
      our own outlook and gain a better understanding of this disorder.

PMID- 22880329
TI  - [School phobia, family, school, and society].

PMID- 22880330
TI  - [From truancy to school phobia].
AB  - The psycho-corporal turbulence which young people undergo during adolescence
      requires support from their family and school to help them succeed in their
      learning and to become independent. An analysis of the upheavals faced by young
      people and of their ties with their family and their peers enables the risk of
      school refusal to be identified and early preventative actions to be put in
      place.

PMID- 22880331
TI  - [Bibliography. School phobia].

PMID- 22880332
TI  - [Childhood obesity and general medicine].
AB  - The results of a 2009-2010 survey of general practitioners in Maine-et-Loire show
      that their practices have improved over the last few years with regard to the
      prevention and treatment of childhood obesity. However, the recommendations of
      the French national health authority and the French national nutrition and health
      programme are not sufficiently applied and doctors face numerous difficulties,
      including a lack of parental involvement.

PMID- 22880333
TI  - Timely action essential to prevent care scandals.

PMID- 22880334
TI  - Inquest and preventable deaths turn spotlight on fundamental care.

PMID- 22880335
TI  - Unions call for decisive action on 1.2 pounds sterling social care funding gap.

PMID- 22880336
TI  - Staff on new course told to use 'gut instinct' to avoid work stress.

PMID- 22880337
TI  - Security tightens at Stepping Hill one year on from saline deaths.

PMID- 22880338
TI  - Staff face ever-closer scrutiny in bid to ensure quality of care.

PMID- 22880339
TI  - Lessons from history offer insight into today's professional practices.

PMID- 22880340
TI  - In splendid isolation.
AB  - Nurses serving communities on the UK's remote islands are using advanced skills
      in roles that, in many cases, were traditionally filled by doctors. Often working
      alone, they take on a high level of responsibility. Those who relish island life
      enjoy the wild beauty of the location and their close relationship with patients.

PMID- 22880341
TI  - Home-cooked care.
AB  - Hospital patients undoubtedly benefit when visitors bring in home-cooked meals.
      Patients are more likely to be well-nourished if they can eat food they enjoy.
      But it can present practical difficulties. Banning such food can prevent visitors
      from showing they care and present nurses with a dilemma.

PMID- 22880342
TI  - Getting back to school.
AB  - Two nurses in Essex are tackling absenteeism among primary school pupils by
      educating children and their parents about how to manage minor illnesses. The
      school liaison nurses provide a telephone helpline and home visits, and support
      with the management of chronic conditions such as asthma.

PMID- 22880343
TI  - Cells and cell biochemistry.
AB  - This article, which forms part of the life sciences series, aims to promote
      understanding of the basic structure and function of cells. It assists healthcare
      professionals to appreciate the complex anatomy and physiology underpinning the
      functioning of the human body. Several introductory chemical concepts and terms
      are outlined. The basic building blocks of all matter, atoms, are examined and
      the way in which they may interact to form new compounds within the body is
      discussed. The basic structures and components that make up a typical cell are
      considered.

PMID- 22880344
TI  - Diagnosis and management of patients with Raynaud's phenomenon.
AB  - This article describes the characteristics of Raynaud's phenomenon, focusing on
      the role of the specialist nurse in diagnosis and management of the condition.
      Pharmacological and non-pharmacological treatment options are discussed, along
      with the importance of self-management. Advice is provided to help nurses enable
      patients to minimise episodes and improve symptoms. In the majority of cases,
      Raynaud's phenomenon is a treatable condition, and patients can learn to self
      manage the disease.

PMID- 22880346
TI  - History taking.

PMID- 22880345
TI  - Motor neurone disease: an overview.
AB  - Motor neurone disease (MND) is a relatively rare, progressive and incurable
      neurological condition affecting patients' speech, mobility and respiratory
      function. Care of patients with MND is complex and involves various healthcare
      professionals and services. There is a need to discuss symptom management and
      promote palliative and end of life care from the point of diagnosis to ensure
      appropriate holistic care is provided.

PMID- 22880347
TI  - On-screen revolution.

PMID- 22880348
TI  - Ready for the games to begin.

PMID- 22880349
TI  - Ready for university.

PMID- 22880350
TI  - Inspiring leaders.

PMID- 22880351
TI  - Working as second-class citizens.

PMID- 22880352
TI  - Repeating employment law history.

PMID- 22880353
TI  - HCAs have legitimate place in staff mix.

PMID- 22880354
TI  - A sister seeks information.

PMID- 22880355
TI  - Disappointment at low constitution vote.

PMID- 22880356
TI  - Pay in aged care 'a form of modern day slavery.

PMID- 22880357
TI  - Rationed care a reality in New Zealand hospitals.

PMID- 22880358
TI  - Nurses must fight TPPA threat.

PMID- 22880359
TI  - Nursing leadership qualities come in many guises.

PMID- 22880360
TI  - Managing after hours--a complex and diverse role.

PMID- 22880361
TI  - Modern advances in wound care.

PMID- 22880362
TI  - Survey looks at issues facing clinical nurse specialists.

PMID- 22880364
TI  - Compassion fatigue--what it is and how to avoid it.

PMID- 22880363
TI  - Changing practice to improve care.

PMID- 22880365
TI  - A return to the nasty '90s.

PMID- 22880366
TI  - Haere ra, Aunty Queenie.

PMID- 22880367
TI  - Primary health care funding and utilisation of nurses has to change.

PMID- 22880368
TI  - [Update on Current Care guidelines: obesity (children)].
AB  - Childhood obesity is an increasing health problem. There may be possibilities to
      prevent obesity in childhood, and efficient interventions to treat obese children
      have been published. Local and regional strategies to prevent and to treat
      childhood obesity are needed.

PMID- 22880369
TI  - [Chlamydia carrier--symptomless or unfaithful?].
AB  - While chlamydia is the most common cause of sexually transmitted infection both
      in Finland and globally, it is not possible to determine the traditionally
      understood incubation period or the time to the development of clinical symptoms.
      Although the knowledge about the disease burden of chlamydial infections has
      grown and its diagnosis and treatment have dramatically improved, there is no
      indication of chlamydia epidemics calming down. Well over 10000 yearly cases are
      still diagnosed in Finland. Active testing or screening still remains essential.

PMID- 22880370
TI  - [Substitution therapy with berries].
AB  - Flavonoids and other polyphenols may explain part of the health effects of red
      wine and cocoa. Owing to their beneficial nutrient content berries are, however,
      even better and more versatile sources of polyphenols. Although few clinical
      studies of health effects of berries are currently available, the results can be
      considered encouraging. Consumption of berries seems to lower the blood pressure
      and improve blood lipid levels in persons having an increased risk of
      cardiovascular diseases. On the whole, substituting unhealthy foods in the diet
      with berries and other plant foods is an excellent way of improving one's health.

PMID- 22880371
TI  - [Piercings--what the physician needs to know?].
AB  - Body piercing (BP) is defined as penetration of jewellery through the skin. Along
      with tattooing BPs are the most common body modifications. Complications related
      to piercing are numerous. They can be acute or chronic, infectious or non
      infectious and local or systemic complications. Acute infections constitute the
      most important complications and occur independently of the piercing site.
      Special attention should be brought on oral piercings, as they are frequent and
      responsible for numerous complications. A non-judgmental approach is recommended,
      when a pierced patient seeks medical help for a piercing complication or any
      other health issue.

PMID- 22880372
TI  - [Intestinal parasite infections].
AB  - Symptoms in a diarrhea patient are most commonly due to a virus or a bacterium,
      but they may also be caused by a parasite. A long incubation period is typical of
      intestinal parasite infections, and in addition to diarrhea they cause prolonged
      symptoms such as abdominal pain and nausea. Parasitic cyst forms are secreted
      with feces and are highly tolerant against various environmental conditions. The
      infections are caught via fecally contaminated food or drink. The diagnosis is
      based on a formalin-fixed fecal parasitic specimen, leading to further
      investigations when necessary.

PMID- 22880373
TI  - [Where do drugs end up in the environment?].
AB  - A large part of harmful substances ending up to the water environment along with
      wastewaters is derived from consumer chemicals, drugs as well as surface
      treatment and flame retardant substances. The cocktail blending from them and
      causing environmental load may cause reproductive disorders to organisms,
      possibly reflecting to the whole population over a long time. Furthermore,
      combined effects of the substances are unknown. The consumption of medicines has
      greatly increased over the past decades, whereby environmental responsibility
      should be called for both in manufacture and trade by pharmaceutical companies.
      Consumers should be informed about proper disposal of medicaments.

PMID- 22880374
TI  - [New infectious diseases in Finland--caused by climate change?].
AB  - Although the appearance and spreading of most new infectious diseases are likely
      to be due to globalization or socio-economic changes, the occurrence of tick-,
      insect- and rodent-borne infections is at least partially dependent on climate
      variability and change. Climate influences the distribution and life cycle of
      vectors of arthropod-borne viruses as well as viral evolution and efficacy of
      transmission. The natural circulation of many pathogens and the development of
      epidemics are dependent on complex ecological factors, such as biodiversity and
      predator-prey cycles that in turn are indirectly linked to climate.

PMID- 22880375
TI  - [Summer beef barbeque--a health risk?].
AB  - The consumption of poultry and pork meat has increased in Finland, but beef has
      become slightly less favored. Summer is, however, the season for barbequing, many
      people buying more meat and sausages than normally. The increase in the usage of
      red or processed meat has a linear association with a growing risk of intestinal
      cancer. For each 100 g of grilled meat, 200 g of vegetables should be grilled or
      eaten as salad.

PMID- 22880376
TI  - [Trampoline injuries in children].
AB  - Trampolines for home use have become common in Finland during the past ten years,
      being especially favored by children. Trampoline jumping is beneficial and
      constructive physical exercise, but poses a significant risk for injuries. The
      most common injuries include sprains and strains. During summertime, trampoline
      injuries account for as many as 13% of children's accidents requiring hospital
      care. Fractures are by far the most common trampoline injuries requiring hospital
      care. Injuries can be prevented by using safety nets. Only one child at a time is
      allowed to jump on the trampoline.

PMID- 22880377
TI  - [Psychologic health effects of summer vacation and other leisure time].
AB  - Successful recovery from workload promotes well-being and functional capacity. It
      requires breaking away from work and restoration of resources used up at work.
      Even a short vacation is beneficial. Physical activity and performing tasks
      bringing self-pleasure will promote vacation effects towards well-being. The more
      loaded the worker, the longer is the necessary period of breaking away from work.
      Since the vacation effects towards well-being vanish quickly, it is good to
      allocate vacations throughout the year, taking care of having breaks and
      opportunities for recovery also during everyday life.

PMID- 22880378
TI  - [The Department of Prevention and the Community Health Districts a territorial
      alliance: strategies for health].
AB  - Health care is promoted thanks to the collaboration between the hospital and the
      territory, with the territory being represented by the Department of Prevention
      and the Community Health District. In the past few years, the territory has
      become increasingly visible with respect to the hospital thanks to its capacity
      to take responsibility for the care of citizens of the local community. These
      three structures in any case must network especially when health data must
      circulate freely in order to be used by the stakeholders. Some changes that the
      Community health district have been faced with such as care of chronic medical
      diseases have been a result of initiatives from the Department of Prevention such
      as screening.

PMID- 22880379
TI  - [Increasing childhood immunization coverage by establishing structured
      relationships with pediatricians and family practitioners].
AB  - An immunization strategy can take advantage of various tools, among which the
      pediatrician and family practitioner These figures, have been assigned the role
      of accompanying the child and his/her family throughout development. One of the
      objectives of this role is also to take a major part in the support of
      immunization coverage of infants, especially in light of the sospension of
      required immunizations in the Veneto Region. For this reason it is necessary to
      open dialogue on immunizations together with pediatricians and family physicians.
      In addition, training of these professional figures, together with healtcare
      operators who work in the immunization clinics, has allowed the formation and
      standardization of the network, as the persons who attend the immunization
      clinics are no longer passive users but persons who require information exchange
      in order to make an informed choice about immunizations for their children.
      Surveillance of vaccination coverage is a useful tool for evaluating the trend in
      vaccination refusals, and in particular it takes into consideration the
      motivation behind the refusal to adhere to the polio vaccine recommendations even
      if for now the coverage is maintained above 95%. Concluding, another strong point
      for the immunization program is "Genitori Piu" which finds its continuity with
      the Regional Prevention Plan.

PMID- 22880380
TI  - [Increasing immunization coverage by intervening on determinants of refusal].
AB  - With the regional decree 3664/2008, the Veneto Region adopted measures for
      improvements in the immunization program, among which the "Investigation into
      determinants for vaccine refusal in the Veneto Region", entrusted by the
      Department of Prevention Local Health Unit 20 (Ulss 20) of Verona. The objective
      of the study was to understand which type of parent that accessed immunization
      services (total adherent, partial adherent or complete refusals) and what factors
      lead to their choice regarding immmunizations in order to better plan strategies
      to maintain vaccination coverage.

PMID- 22880381
TI  - [Increasing immunization coverage in adults and elderly by creating structural
      relationships with general practitioners].
AB  - In order to reach vaccination coverage in adults, the elderly and in high risk
      subjects, a tight network of collaboration between preventive medicine
      specialists and general practitioners must be created in the same way that they
      must be created with pediatricians. In fact, this strategy has brought about very
      high coverage rates in childhood vaccinations. The solution to propose once again
      would thus be to develop partnerships between the protagonists of the network
      (community health district, department of prevention, general practitioners,
      primary care physicians) so that synergies may be created which permit the
      realisation of common and specific training programs.

PMID- 22880382
TI  - [Improving air quality in urban centers: the Bologna experience].
AB  - Among the themes addressed in public health, environmental hygiene represents a
      good example of how certain questions can be resolved through the construction of
      strongly integrated operative networks. In particular when one speaks of air
      quality in urban centers there must be an awareness that there should be
      coordination of all actors involved. In this way the Department of Prevention can
      transform itself into the essential part of the hub thanks to its specific skills
      and expertise. In this discussion, some experiences of the Local Health Agency of
      Bologna where the Department of Prevention could become the hub of the system
      will be presented.

PMID- 22880383
TI  - [Improving dietary habits in the effective prevention of excess weight and
      obesity].
AB  - The new research survey "Okkio alla salute", conducted in children in the 3rd
      year of elementary school, has confermed the worrisome phenomenon of the high
      number of obese and overweight children. Therefore, it is necessary, also in
      light of the few available resources, to fight back against this phenomenon that
      has been demonstrated to be a cause of disabling illnesses in adults. There must
      therefore be collaboration between Departments of Prevention and Hygiene and
      Nutrition services (SIAN) to build valid and efficient pathways. In this
      presentation we describe some national projects carried out by various local
      health agencies to address this health problem.

PMID- 22880384
TI  - [Improving public health and hygiene surveillance activity: the Lombardy
      experience].
AB  - In light of changing health needs, it has become a necessity to modify the
      instruments used in prevention, and this is thanks also to all the new preventive
      health professions that have been added to the existing ones. This presentation
      describes the results of the activities of prevention and control of occupational
      injuries, environmental hygiene and food and nutrition security in the Lombardy
      Region.

PMID- 22880385
TI  - [The network of palliative care for persons with incurable disease in the Local
      Health Agency n. 7 of the Veneto region].
AB  - Only 20% of terminally ill people with cancer in Italy are assisted by a network
      of palliative care, whereas the majority of them die in the hospital, against
      their will, and with very low doses of opioids. A palliative care service, is
      offered by the Nucleus of Palliative care within the Operative Unit of District
      Primary Care in the local health agency n. 7 of Pieve di Soligo. This service
      takes charge of the patient from hospital discharge until his/her death, working
      in concert with the inpatieint hospitals and other territorial health care
      structures. In this way, the patient and his/her family are followed by a team of
      professionals working together in coordination and collaboration. In 2010 the
      percentage of terminally ill persons enrolled in the program was 52%, much
      greater than the standard of 45% required by ministerial law (DM no 43 del 2007)
      for the local health agencies without a hospice. The duration of time spent at
      home during the last phases of the illness was over 90% of time in care, with an
      in-home mortality of 63%. The consumption of major opioids was amongst the
      highest in Italy. Thanks to the opening of a hospice, already planned, we will be
      able to take charge within the network of palliative care thos sick people who
      cannot remain in the home and extend the service to ill persons without cancer in
      conditions of advanced incurable disease and end of life.

PMID- 22880386
TI  - [Organization of colon-rectal cancer screening in the Provincial Health Agency of
      Ragusa].
AB  - Cancer screening is a secondary prevention program that permits early diagnosis
      of neoplasias and precancerous lesions are in order to diminish mortality and
      morbidity for certain types of tumors (breast, colon-rectal, and cervical). In
      2010, the Ragusa Provincial Health Agency began screening for colon-rectal cancer
      in an experimental phase that initially involved only the municipality of Ragusa
      but that was then extended to other municipalities of the province. Although the
      organizing model suffered from many managerial problems including lack of human
      resources and tools, there was good collaboration and involvement of the public
      health/hygiene offices and the general practitioners and volunteer associations.
      This type of networking was useful in that adhesion to screening was well above
      that expected. Another winning aspect of the project resulted in clear and
      pertinent communication to the population.

PMID- 22880388
TI  - Concluding comments.

PMID- 22880387
TI  - [Evaluation and containment of cardiovascular risk in a large number of "healthy"
      subjects].
AB  - Cardiovascular diseases are the primary cause of death and represent a public
      health problem both in terms of mortality and morbidity. Since many risk factors
      for cardiovascular disease can be corrected with active interventions, we
      proposed a structured model operating in ways similar to cancer screening: active
      recall of healthy subjects, offers to intervene in selected subjects. In the
      experimental model adopted by the Local Health Unit n. 17--Este and the Local
      Health Unit n. 7--Pieve di Soligo, after pre-evaluation/exclusion by the general
      practitioner subjects aged between 45 and 59 years were recalled and evaluated by
      a trained health assistant using anthropometric measurements, screening blood
      pressure, fasting blood glucose, and evaluation of lifestyle. If their values
      were abnormal, the health assistant invited them to participate, and counseled
      them on some initiatives to make changes. The proposed model was demonstrated to
      be a good model both because using previously tested structured models, it
      revealed an elevated number of subjects with hypertension and hyperglycemia that
      were before undetected and because it placed up front strategic actions of the
      Prevention Departments. In addition, in follow-up, improvements in lifestyle were
      seen in subjects who had been counseled to alter them.

PMID- 22880389
TI  - [Microorganisms as phytase producers].

PMID- 22880390
TI  - [Genetic differentiation of yeasts alpha-glucosidases: maltase and isomaltase].

PMID- 22880391
TI  - [Molecular identification of bacteria and archebacteria in acid lakes in Northern
      regions of Russia].

PMID- 22880392
TI  - [Biooxidation of gold sulfide concentrate in different physical-chemical
      conditions].

PMID- 22880393
TI  - [3-hydroxybenzoate and 2,5-dihydroxybenzoate metabolism in Rhodococcus opacus 1CP
      strain].

PMID- 22880394
TI  - [Secondary metabolites profile in Penicillium genus isolated from Arctic and
      Antarctic permafrost, polyphase taxonomy ].

PMID- 22880395
TI  - [Creation of mutants of Shewanella oneidensis MR-1 with increased reduction
      activity].

PMID- 22880396
TI  - [Capsular and extracellular polysaccharides of diazotrophic rhizobacteria
      Herbaspirillum seropedicae Z78 ].

PMID- 22880397
TI  - [Escherichia coli M-17 lipopolysaccharide].

PMID- 22880398
TI  - [Molecular phylogeny and taxonomy of filamentous sulfur bacteria of Thiothrix
      genus].

PMID- 22880399
TI  - Immunological and biological relationship among flagellin of Pseudomonas
      aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia.
AB  - The flagellar protein (flagellin) was isolated and purified from strains of
      Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia. A
      significant difference was observed in the molecular weight of different
      flagellin preparations obtained from these bacterial isolates. Antiserum prepared
      against S. maltophilia flagellin did not react with flagellin of P. aeruginosa
      or/and B. cepacia on Immunoblot or in indirect ELISA. In addition the anti
      flagellin did not agglutinate P. aeruginosa and B. cepacia. No inhibition of
      motility of P. aeruginosa and B. cepacia was observed in presence of antiserum;
      though the latter inhibited the motility of S. maltophilia. The results of the
      present study prove that no specific relationship existed among all the studied
      flagellar proteins obtained from closely related bacteria.

PMID- 22880400
TI  - [Bacterioplankton of Poland region of Baltic sea].

PMID- 22880401
TI  - [Picophytoplankton of Velikaia Salma channel of White sea].

PMID- 22880402
TI  - [Brown algae metabolites influence on o-glycoside hydrolases synthesis of
      bacteria degrading Fucus evanescens tallom].

PMID- 22880403
TI  - [Alpha-n-acetylgalactosaminidases of algal sea bacteria Bacteroidetes phylum in
      Okhotskoe and Japan seas ].

PMID- 22880404
TI  - [Variants of gastric carcinomas according to immunohistochemical mucins and CD10
      expressions].
AB  - Mucins and glycoprotein CD10 expression in 55 carcinomas of the stomach has been
      studied by immunohistochemistry. According to a profile of mucins and CD10
      expression, 3 immunophenotypic variants of carcinoma were founded: gastric,
      intestinal and gastro-intestinal. Gastric and gastro-intestinal variants were
      more frequently than intestinal one. The correlation between the expression of
      investigated markers and histological type of carcinoma wasn't revealed The
      estimation of Ki-67 index has shown that the highest proliferative activity
      (>20%) in carcinomas with gastric phenotype has been found more often than in
      gastro-intestinal ones.

PMID- 22880406
TI  - [Allelic disbalance in 1q32 area and microsatellite instability renal papillary
      adenocarcinoma].
AB  - Papillary adenocarcinoma is an abundant form of renal cell carcinoma. At present
      any diagnostic and prognostic molecular markers of papillary adenocarcinoma are
      absent, however some cytogenetic and molecular-genetic features of disease are
      known. According to literary data, the 1q32 duplication is associated with
      progressive deterioration of primary tumor. We have done a genetic typing
      (D1S2142 and D1S3465 locus) of 39 papillary adenocarcinoma cases, used PCR and
      fragment analyses of the 1q32 area. Frequency of the allelic disbalance was
      36.8%; the microsatellite instability was found out in 48.7% of cases. The
      association of genetic disturbances with clinic-morphological features of
      papillary adenocarcinoma wasn't revealed. In some cases genetic heterogeneity of
      tumor-adjacent renal parenchyma and primary tumors was found out at multifocal
      renal carcinoma. For the first time we ve demonstrated that the allelic
      disbalance in 1q32 area and the microsatellite instability are frequent molecular
      genetic disturbances in sporadic papillary carcinomas at all stages of the
      disease. Probably, the microsatellite instability is connected with progressive
      deterioration of primary tumor at renal papillary adenocarcinoma.

PMID- 22880405
TI  - [Hormonally inactivated pituitary adenoma: morphological, immunohistochemical and
      electron-microscopic characteristic].
AB  - Morphology of hormonally inactivated pituitary adenoma can be different types of
      tumors. Morphological immunohistochemical and electron-microscopic researches of
      23 hormonally inactivated pituitary adenomas has been carried out. We shown that
      more frequent morphological substrate was gonadotropinoma or "zero-cells"
      adenoma. According to our results, gonadotropinomas, "zero-cells" adenomas and
      oncocytomas have similar features and can be put into the same group of tumor
      Pathomorphologist has to differentiate this group of tumors from others "silent"
      pituitary adenomas because they have different prognosis for a disease. A
      research of somatostatin and dopamine receptors expression would be new area for
      differential diagnosis of these types of adenomas.

PMID- 22880407
TI  - [Molecular markers of colorectal adrenocarcinoma progression].
AB  - Colorectal adenocarcinoma and its lymph node metastases from 72 patients and 14
      control samples were studied. Expression of adhesive molecules - E-cadherin and
      beta-catenin, antiadhesive molecule - tenascin C and tumor metastasis suppressor
      KAI-1 (CD82) were studied by immunohistochemistry. The expression of E-cadherin
      and beta-catenin, tenascin C and KAI-1 was significantly different in
      adenocarcinoma and control samples. The expression of E-cadherin, tenascin C and
      KAI-1 was diverse in primary tumor compared to lymph node metastases. The
      analysis of current data showed the association of E-cadherin expression with
      stage of disease and depth of invasion, such as the correlation of beta-catenin
      nuclear expression and tenascin C expression with depth of adenocarcinoma
      invasion. These data may be a useful indicator of disease progression.

PMID- 22880408
TI  - [Chromogenic in situ hybridization in diagnostics of Epstein-Barr-virus infection
      in chronic tonsillitis].
AB  - In the issue we demonstrate results of Epstein-Barr virus (EBV) detection by
      chromogenic in situ hybridization (CISH) in epithelial and lymphoid cells of the
      palatine tonsil in patients with chronic tonsillitis. Virus genome detections
      were performed using RNA-probes with digoxigenin-labeled oligonucleotides which
      target EBV RNA, notably RNA-transcripts of virus genomic DNA. The obtained data
      confirm the virus lymphotropism and also tropism to epithelial cells of both
      surface and cryptal epithelium of the palatine tonsil. CISH method in combination
      with immunohistochemical identification of virus protein products opens new
      possibilities for clinicopathological monitoring of the different clinical forms
      of the chronic tonsillitis, as well as new horizon for understanding intrinsic
      role of EBV in tonsillar pathology.

PMID- 22880409
TI  - [Immunomorphology of recurrent aphthous stomatitis].
AB  - The immunohistochemical investigation of native epithelium and recurrent aphthous
      stomatitis has been carried out. The A, M, G Igs, CD3 fragment of the compliment,
      and CD16 lymphocytes in the zone of gidropic changes and necrosis of the oral
      mucosa were founded The distribution of Igs, CD3 fragment of the compliment and
      natural killers in the same zone - prickle laminated keratinizing epithelium
      could be signs of immunocomplex and T-cell-dependent mechanisms of ceracinocytes
      dies. The results of our research prove the theory of immunotoxicity priority in
      oral mucosa in cases of recurrent aphthosus stomatitis.

PMID- 22880410
TI  - [Anchoring villi are sources of cytotrophoblastic invasion in the second
      trimester of physiologic pregnancy].
AB  - The basal laminas and fixed on them anchoring villi after late abortion on 18-28
      weeks of pregnancy have been studied. The pregnancies were without complication
      and abortions were activated by "Enzaprost" injection. 4 types of anchoring villi
      were studied: without cytotrophoblastic invasion, with maximal, medium and
      minimal density of cytotrophoblastic distribution and depth of its invasion into
      endometrium from villi's base. The maximum of its migration activity was in 18-20
      and 22-23 weeks of pregnancy. The activity decay of cytotrophoblastic invasion
      was been found in the end of the second trimester Anatomic contact of villi's
      base with endometrium increased by them parallel attachment or horseshoe-shaped
      form. The estimation of villi's quantity and density of cytotrophoblastic
      distribution in their base can use for definition of cytotrophoblastic invasion
      rate in the adjacent myometrium of pregnant women on the second trimester.

PMID- 22880411
TI  - [Age-related dynamics of structure changes in the 17th cortical area of children
      with perinatal affection of the nervous system].
AB  - Brain autopsy of children standing afterperinatal affection of the nervous system
      and healthy children without any neurological disorders (a control group) has
      been studied by computers morphometric methods. The age-related dynamics of
      structure parameters in the 17th cortical area was investigated. Correlation
      between increasing of cortical lamina's diameters and age of children with
      perinatal affection of the brain wasn't revealed. The width of IVand V cortical
      layers, size of neurons and their density in the cortex of children with
      perinatal pathology were significantly fewer than in the control group. However
      the density of glia including GFAP-positive astroglia in the children with
      prenatal pathology was higher to compare with the control group. We suggest that
      detected disorders are signs of nonspecific structure-functional changes in the
      visual cortex and follows destructive and compensatory restorative reactions.

PMID- 22880412
TI  - [Features of cardiomyocytes structural changes in patients with postinfarction
      aneurism and reduced myocardial contractility of the left ventricle of the
      heart].
AB  - Cardiomyocytes (CMC) of 18 patients with both ischemic heart disease, aneurism of
      the front wall and reduced myocardial contractility of the left ventricle (LV)
      were hypertrophied and in state of chronic hibernation, which was characterized
      by weakening of tissue-specific signs. Widening of lack myofibrils' zones and in
      part gap junction of intercalated disk transfer on the side of cells was found
      The hypertrophy of CMC had positive correlation, but chronic hibernation -
      negative one with the volume of LV. The worse prognosis of clinical course was
      degenerative changes of hibernate CMC with accumulation of autophagosomes that
      correlated with increasing of LV sphericity index.

PMID- 22880413
TI  - [Myocardial signs of cardiotoxicity].
AB  - The myocardium have been get from 70 died patients suffered from schizophrenia
      and treated by neuroleptic drugs. The cardiotoxic effect of neuroleptic drugs was
      characterized as adaptive, degenerative, and fibrous changes in the miocardium.
      In the extracellular matrix of the myocardium the processes of microcirculation
      and the collagenogenesis were damaged. As a result of the using neuroleptic drugs
      a compensatory hypertrophy of cardiomyocytes was transformed into their
      degeneration and atrophy that could be reason of a heart failure.

PMID- 22880414
TI  - [Morphological features of pulmonary and thymic carcinoid tumor].
AB  - Morphological features of atypical and typical subtypes of pulmonary and thymic
      carcinoid tumors have been studied by pathohistological, immunohistochemical and
      electron-microscopic methods. There are the main principles of differential
      diagnostics in the article.

PMID- 22880415
TI  - [HER-2/neu-testing in breast cancer: is the immunocytochemistry competent?].
AB  - According to ASCO/CAP guidelines, there are two recommended methods for Her2/neu
      testing in breast cancer patients such as immunohistochemistry and fluorescence
      in situ hybridization. This paper analyses results of alternative
      immunocytochemical method for Her2/neu detection and its diagnostic pitfalls.

PMID- 22880416
TI  - [Different Her-2 status in infiltrative and intraductal components of the breast
      cancer].
AB  - In the article a breast cancer case with different Her2 status in invasive and
      non-invasive components is described. We emphasize on the importance of knowledge
      about tumor histology for correct interpretation of FISH Her2-test results.

PMID- 22880417
TI  - [Breast silicone granulomas].
AB  - With the lapse of time, silicone leakage from breast implants leads to the
      formation of giant cells granulomas and fibrous capsule with calcification caused
      painful sensation. The morphogenesis of tissue changes around implants, which has
      been persistence up to 12 years, are described.

PMID- 22880418
TI  - [Adrenal cortical carcinoma: an autopsy case].
AB  - In the review are available literature data about different types of adrenal
      cortical carcinomas. The case described for the first time diagnosed
      incidentaloma in an 86-year-old man has been characterized. This observation is
      valuable because of the rarity of pathology and the difficulties of clinical
      diagnostics.

PMID- 22880419
TI  - [Morphological signs of mitochondrial cytopathy in skeletal muscles and micro
      vessel walls in a patient with cerebral artery dissection associated with MELAS
      syndrome].
AB  - Skin and muscles biopsy specimens of a patient harboring A3243G mutation in
      mitochondrial DNA, with dissection of internal carotid and vertebral arteries,
      associated with MELAS were studied using histochemical and electron-microscopy
      techniques. Ragged red fibers, regional variability of SDH histochemical
      reaction, two types of morphologically atypical mitochondria and their
      aggregation were found in muscle. There was correlation between SDH histochemical
      staining and number of mitochondria revealed by electron microscopy in muscle
      tissue. Similar mitochondrial abnormality, their distribution and cell lesions
      followed by extra-cellular matrix mineralization were found in the blood vessel
      walls. In line with generalization of cytopathy process caused by gene mutation
      it can be supposed that changes found in skin and muscle microvessels also exist
      in large cerebral vessels causing the vessel wall "weakness", predisposing them
      to dissection.

PMID- 22880420
TI  - [Diffuse lymphangioleiomyomatosis of lung: case report].
AB  - In the article the case of diffuse lymphangioleiomyomatosis of the lung at 21
      year-old women is described The disease has manifested on the 38th week of the
      pregnancy. Leiomyomas of others localizations were absent. The clinical course
      was malignant: in 22 days after disease's manifestation women had died. The
      possible mechanisms of uncontrolled proliferation of nonstriated muscle's
      elements and features of lymphangioleiomyoma's morphological diagnostics are
      discussed.

PMID- 22880421
TI  - [The role of N.I. Pirogov in the development of pathological anatomy].

PMID- 22880422
TI  - [The armed force institute of pathology in USA (AFIP) was closed].

PMID- 22880423
TI  - [Girej Alievich Bairov (1922-1999) (to his 90th birthday)].

PMID- 22880424
TI  - [The role of endoscopic methods in treatment of tracheal cicatricial stenoses].
AB  - Treatment of tracheal cicatricial stenosis is one of the most difficult problems
      of modem medicine. There are two main therapeutic approaches--endoscopic
      (bronchoscopic) and surgical (open). The paper describes the methods of
      endoscopic treatment of stenoses allowing achieving complete recovery of tracheal
      lumen in some cases. The scheme of treatment for tracheal cicatricial stenosis is
      also described.

PMID- 22880425
TI  - [Results of combined reconstructions of the renal arteries, abdominal aorta and
      its other branches in patients with atherosclerosis].
AB  - A comparative analysis was made of clinical indices and long-term survival in 20
      patients (13 men and 7 women of mean age 62 +/- 2 years), having multifocal
      atherosclerosis of the renal arteries (RA), abdominal aorta and arteries of lower
      extremities (LE) (11 aneurysms, 7 occlusive lesions of the aorta and 3 of its
      unpaired branches) who underwent combined reconstructions, with patients having
      similar lesions, but not operated (12) or operated only on RA or on the arteries
      of LE (45). The groups of patients had no great differences except more
      pronounced renal dysfunction (RD) in the first of them. In spite of high
      postoperative lethality (20%) mainly due to acute renal failure (3), long-term
      survival proved to be significantly higher (14 from 16), than in not operated (3
      from 12) (p = 0.00001) and had better tendency than in those operated on the same
      basin (35 from 45). In addition, the patients after combined operations had
      substantially decreased systolic and diastolic arterial pressure (159 +/- 13 vs.
      132 +/- 9, p = 0.00001; 91 +/- 5 vs. 83 +/- 7, p = 0.010) and also stabilized
      renal function.

PMID- 22880426
TI  - [Osteoiliacography as diagnostic method of vena cava inferior circulation failure
      in liver cirrhosis].
AB  - Hypertension developing in the vena cava system under conditions of cirrhosis
      results in the formation of collateral blood outflow into vena cava superior
      (VCS) and inferior, at the same time the carrying capacity of vena cava inferior
      (VCI) might be limited due both to its fixation in the rigid diaphragm ring and
      to the fact that the hepatic segment of VCI is compressed by regenerated nodes.
      The increased volume of blood outflow via VCI with a simultaneous constriction of
      its hepatic segment results in the development of caval hypertention which even
      more complicates the transhepatic blood flow. Increased pressure in the VCI
      system with the formation of suprahepatic postsinusoidal block creates additional
      considerable barriers for blood outflow from the liver aggravating the failure of
      portal circulation, creating vicious circle that leads to decompensation of both
      regional visceral and common venous hemodynamics. The author describes the method
      of diagnosing cava-caval crossflows from VCI to VCS. The condition of VCI and
      cava-caval crossflows under liver cirrhosis is an important component in complex
      diagnostics.

PMID- 22880427
TI  - [Application of biologically active suture materials in emergency surgery of
      abdominal cavity organs].
AB  - An investigation of specific course of the wound process and near results of
      operations on 398 patients with emergency abdominal surgical pathology has
      revealed advantages of using new biologically active suture materials "Nikant"
      (with doxicyclin) and "Nikant-P" (with doxicyclin and stimulator of regeneration
      from the group of hermanium-containing organic compounds) in performing surgical
      interventions. Total number of patients with complications at the early
      postoperative period, operated using threads "Nikant" (38-29.9%) and "Nikant-P"
      (30-23.8%) proved to be reliably less than in patients of the control group (71
      48.9%). The results of operations improved at the expense of considerable
      reduction of the number of postoperative local pyo-inflammatory processes.

PMID- 22880428
TI  - [Principles of direct surgical procedures on the pancreas in surgical treatment
      of chronic pancreatitis].
AB  - An analysis of treatment of 584 patients with complicated forms of chronic
      pancreatitis operated during 2000-2100 years was carried out. Quality of life of
      postoperative patients was estimated according to a technique of calculations of
      modules EORTC QLQ-C30 and EORTC QLQ-PAN26. The indicators of quality of life have
      improved by 19.7% in performance of saving duodenal outflow of operations of
      pancreatic juice. Change of the surgical strategy has led to decreased number of
      postoperative complications by 4.6% and to satisfactory long-term results in
      92.6% of the patients.

PMID- 22880429
TI  - [An analysis of effectiveness of application of various methods of artificial
      detoxication in patients with sterile phase of pancreatic necroses].
AB  - The presented work is based on an analysis of results of conservative and
      surgical treatment of 65 patients in sterile phase of pancreatic necrosis with
      the application of various methods of artificial detoxication. Increased
      efficiency of extracorporal detoxication methods is achieved by an individual
      selection of the detoxication method depending on the basic clinico-laboratory
      indicators of toxemia, phases of endogenic intoxication and accounting the
      mechanism of action of the methods. In the favorable course of the disease
      against the background of complex treatment using artificial detoxication methods
      decreased the basic clinico-laboratory indicators used for monitoring the level
      of endotoxemia and incompetence of the detoxicated bodies and systems as well as
      of severity of the general condition of the patients. Results of the research
      performed point to the greater role of using the extracomporal detoxication
      methods in complex treatment of acute destructive pancreatitis.

PMID- 22880430
TI  - [Usefulness of endoscopic ultrasonography in the diagnosis of choledocholithiasis
      and inflammatory biliary strictures].
AB  - Results of the diagnosis of endoscopic ultrasonography (USG) in 58 patients with
      suspected choledocholithiasis were analyzed. Bile duct stones were diagnosed by
      USG in 54 patients, including 5 patients in combination with terminal bile duct
      strictures. The sensitivity, specificity and accuracy of the USG method in
      detecting choledocholithiasis were 96.3, 100 and 96.5% respectively.

PMID- 22880431
TI  - [Modern aspects of the diagnosis and surgical treatment of perforations of
      chronic gastroduodenal ulcers].
AB  - Results of the complex diagnosis and surgical treatment of 180 patients with
      perforation of gastroduodenal ulcers were analyzed. It was shown that in
      pathogenesis of perforations of chronic gastroduodenal ulcers the leading place
      belonged to oxidizing stress. A pathogenetically grounded method of treatment of
      perforations of chronic gastroduodenal ulcers is an excision of the perforated
      ulcers in combination with vagotomy, but the method of treatment of perforations
      of "silent" ulcers is videolaparoscopic suture with endoscopic transgastgric
      chemical vagotomy.

PMID- 22880432
TI  - [Minimally invasive treatment of pelvic congestion syndrome].
AB  - Complex clinical and ultrasound examination of 81 women with chronic venous
      insufficiency (CVI) of the pelvis was analyzed. All the patients had left-side
      regional renal venous hypertension which caused valvular insufficiency of the
      left ovarian vein with spread of the reno-ovarian blood reflux onto the
      pampiniform, uterovaginal, presacral, vesical and rectal plexuses. Right-side
      cavaovarial reflux of blood was found but in 29.6% of the patients and in
      combination with reno-ovarial reflux caused complete decompression of the venous
      outflow from the pelvis. The treatment was performed depending on the stage of
      CVI of the pelvis. At the stage of compensation (59.3% of patients) complex
      conservative treatment was used, at the stage of subcompensation (17.3%)-
      sclerotherapy, at the stage of decompensation (23.4%)--operative dissection of
      gonad veins. Excellent results were registered in 34.5%, good--in 43.2%,
      satisfactory--in 21%, unsatisfactory in 1.2% of the patients. On the basis of
      self-assessment of quality of life 77.8% of the patients thought to be completely
      restored, 16%--improved, 6.2% of women had no changes.

PMID- 22880433
TI  - [Regional vasoactive and metabolic therapy of patients with severe cranio
      cerebral traumas].
AB  - In patients with severe cranio-cerebral traumas an investigation was performed of
      the efficiency of using vasoactive therapy in complex treatment directed to
      earlier recovery of the microcirculatory blood flow and aerobic metabolism in
      ischemic parts of the brain.

PMID- 22880434
TI  - [The method of replacement of defects in impression fractures of calcaneus.
      Porous NiTi or autotransplant?].
AB  - An experience with treatment of 149 patients with severe injuries of the ankle
      joint operated using constructions of titanium-nickelide and autotransplant from
      the iliac crest is presented. Porous NiTi being bio-inert to organism tissues,
      having high through porosity, the formation of consolidation of the fracture
      develops more rapidly. Application of porous NiTi allowed the period of
      disablement to be on an average 20 days shorter and long-term results to be
      reliably better.

PMID- 22880435
TI  - [Application of the method of continuous suture annuloplasty for mitral valve
      disease of dysplastic etiology].
AB  - Considerable mitral regurgitation of dysplastic etiology was corrected in 63
      patients using the method of continuous suture annuloplasty. The operations were
      fulfilled by the access through median sternotomy, under conditions of
      extracorporeal circulation, blood isothermal cardioplegy. Immediate results show
      effectiveness of correction of mitral insufficiency and safety of using the
      method due to the absence of lethal outcomes, thromboembolic complications and
      the necessity of another surgical correction in the nearest postoperative period.

PMID- 22880436
TI  - [Prophylactics and treatment of complications after resection of the liver].
AB  - Results of treatment of 147 patients with focal diseases of the liver are
      described. Postoperative complications appeared in 25.8%, postoperative lethality
      was 6.7%. Among the postoperative complications the leading role belongs to
      hepatic insufficiency. Prognostic factors of the development of postresectional
      hepatic insufficiency are the degree of liver cirrhosis and dilatation of the
      portal vein, malignant character of the tumor, volume of liver resection, whole
      protein level before operation. The strategy of mini-invasive treatment of
      patients with biliary complications was worked out. Strict selection of patients,
      using blood-saving methods and techniques allow postoperative lethality to be
      decreased.

PMID- 22880437
TI  - [Postnecrotic cysts of the pancreas: possible ways of minimally invasive external
      and internal drainage].
AB  - The authors have shown a possibility of minimally invasive interventional surgery
      in treatment of postnecrotic cysts of the pancreas and their complications. The
      most optimal accesses for drainage of the cavities located inside the body and
      the pancreas head are determined. The use of the methods of internal drainage of
      the cyst cavity connected with the main pancreatic duct allowed avoidance of open
      operations. The results of antegrade percutaneous or transcavital as well as
      retrograde endoscopic restoration of the patency of the main pancreatic duct in
      treatment of the pancreatic cysts connected with the duct system are shown.

PMID- 22880439
TI  - [The method of surgical treatment of closed injury to the pancreas].

PMID- 22880438
TI  - [Successful step-wise revascularization of the kidney and lower extremity in a 20
      year-old patient with congenital total hypoplasia of the aorta].

PMID- 22880440
TI  - [Cancer of the artificial esophagus fifty years after prethoracic plasty].

PMID- 22880441
TI  - [On the question of the development of medical-economic standard of diagnostics
      of oncologic diseases of the upper gastrointestinal tract in outpatient clinics
      of Saint Petersburg].
AB  - The authors investigated general principles and specific development of medico
      economic standard-based data-processing system, "Expert-MES", for early diagnosis
      of tumors of the upper gastrointestinal tract. The method of calculating the
      actual cost of diagnostic measures is demonstrated with regard to necessary
      volumes. The possibilities of monitoring the implementation of MES in request of
      patients for examination in outpatient clinics are evaluated.

PMID- 22880442
TI  - [Metabolic correction of the lipid-transport system in experimental diffuse
      purulent peritonitis].
AB  - The research was performed in 55 male chinchilla rabbits. For the first time the
      effect of metabolic preparations "citoflavin" and "neoton" of the protein-lipid
      spectrum of blood was studied in experimental diffuse purulent peritonitis. The
      development of diffuse purulent peritonitis caused negative changes in blood
      lipid-transport system which resulted in a decreased blood protein level and high
      density lipoproteins (HDL) and growth of triglycerides. In the HDL phospholipid
      spectrum the pathological changes are characterized by an increased
      lisophosphotide content and compensatory growth of the level of
      poliglycerophosphatides. A comparative analysis has shown that both preparations
      possess unidirectional action which is more pronounced in "citoflavin" than in
      "neoton".

PMID- 22880443
TI  - [Comparative assessment of the reparative process of wounds of the liver and
      kidneys depending on the kind of plastic material in experiment].
AB  - In 52 rabbits a morphological assessment was made of regeneration of wounds of
      the liver and kidneys after their plasty with a seromuscle flap of the stomach on
      the vascular pedicle (26 rabbits), of hepatorhaphy and omentonephroplasty (26
      rabbits) within the period from 1 to 360 days and was compared with literature
      data concerning reparation of the liver and kidney of the rabbit with the
      application of bio- and polymer materials for covering their wounds. The
      influence of plastic properties of the materials used on the productivity of the
      inflammatory-reparative process was established. In suturing the wounds of
      parenchymatous organs it is necessary to use plastic materials stimulating
      regeneration. The application of seromuscle flap of the stomach for these
      purposes improves the inflammatory-reparative process making it more productive
      as compared with bio- and polymer materials.

PMID- 22880444
TI  - [Conference "state of emergency surgical care in Saint Petersburg"].

PMID- 22880445
TI  - [Syndrome of "diabetic foot"].

PMID- 22880446
TI  - [Recurrent inguinal hernias].

PMID- 22880447
TI  - [Syndrome of "deficient liver size" after resection and transplantation of a
      liver fragment].

PMID- 22880448
TI  - Actions reducing tobacco smoking at the workplace--do larger and richer companies
      solve the problem better?
AB  - BACKGROUND: Workplaces are an important subject of state policy regarding
      smoking. They are obliged to comply with the prohibition of smoking in public
      places, except special smoking-rooms--if the employer decides to create such.
      This paper discusses the Polish enterprises activity in relation to smoking,
      according to new legal obligations and principles of health promotion programs.
      Furthermore, the article raises the question whether companies' size and economic
      situation differentiate their attitude to smoking. MATERIAL: 1002 interviews
      (computer-assisted telephone interview - CATI) conducted in November/December
      2010 (date of entry into force of the new law regarding smoking at the workplace)
      in a representative sample workplace employing above 50 employees. RESULTS: A
      total smoking prohibition applies in 23% of companies, smoking is allowed only in
      special smoking-rooms and outside the building in 54% of enterprises, in 23% of
      companies regulations are inconsistent with the state policy (for example smoking
      allowed in the corridors). Apart from smoking bans, companies introduce
      disciplinary punishments for breaking them and health education (in the absence
      of other activities promoting non-smoking). In one in three companies' the
      management does not enforce the compliance with the introduced regulations.
      Generally, the management does not see a connection between employees smoking and
      the functioning of the company. In every second company, employees to a greater
      or lesser extent break the smoking ban. Companies' economic situation does not
      differentiate their attitude to the problem, the size of employment only
      slightly. CONCLUSIONS: The results obtained can be used for future evaluation of
      the effectiveness of the state tobacco control policy and proper direction of the
      programs aimed at releasing companies from smoke as well as campaigns prepared
      for employers.

PMID- 22880449
TI  - [Physical activity of top level managers in the context of the public health
      recommendations].
AB  - BACKGROUND: The purpose of the work was to assess weekly, habitual physical
      activity of high-ranking managers, aged 28-63. The research question was
      formulated as follows: What percentage of surveyed professional workers met the
      criteria for health-recommended physical activity? MATERIALS AND METHODS: The
      research involved 123 top level managers divided into three age groups: 28-39, 40
      49 and 50-63 years. Physical activity was measured using the short form of the
      International Physical Activity Questionnaire (IPAQ). The volume of different
      levels of physical activity was calculated in units of MET min/wk. The percentage
      of managers meeting various criteria (IPAQ, Paffenbarger's recommendations,
      American College and Sport Medicine and WHO recommendations) for physical
      activity was calculated. RESULTS: the average total volume of weekly physical
      activity was 2189.39 +/- 1201.44 MET min/wk. Public health recommendations for
      adults issued by the American College of Sports Medicine and the American Heart
      Association were met by only 27% of managers. CONCLUSIONS: Manager's average
      frequency of participation in moderate and vigorous physical activity is lower
      than recommended. There is a need to institute programs to promote healthy
      behavior (especially physical activity) among high-ranking professional workers.

PMID- 22880450
TI  - [Preliminary evaluation of musculoskeletal pain disorders reported by private
      farmers].
AB  - BACKGROUND: According to the data recorded by the European Agency for Safety and
      Health at Work, nearly 24% of employees from the EU-25 countries complain of back
      pain, while 22% report muscular pain. MATERIALS AND METHODS: The study covered a
      selected group of 58 male farmers, inhabitants of 7 districts in the Lublin
      region, engaged in the mixed agricultural production (plant-animal), aged 54.9 +/
      10.1. The control group comprised 41 researchers of the University of Life
      Sciences and the Institute of Rural Health, aged 48.9 +/- 9.6. The basic research
      instrument was a self-designed questionnaire on pain complaints occurring within
      the motor system: in the lower and upper parts of the spine, and in the region of
      the neck and shoulders. RESULTS: The results of the survey showed that of the
      four regions of the motor organs examined, the farmers reported most frequently
      pain complaints in the lower part of the spine (54 farmers; 93.1% of the total
      number of respondents), whereas in the control group, pain in this region was
      reported by 63.4% of researchers (p = 0.0002). Lower back pain most often
      occurred in farmers during their entire occupational life (64.8%), while in the
      control group this type of pain had occurred in the last 12 months (57.7%).
      Farmers described this pain as permanent, radiating to one or both legs, whereas
      in the control group these were short-lasting episodes (less than 14 days).

PMID- 22880451
TI  - [Analysis of quality of life in patiens with low back pain after receiving
      transcutaneous electrical nerve stimulation (TENS)].
AB  - INTRODUCTION: Low back pain (LBP) is one of the most common disorders affecting
      office employees working with a computer, which inevitably leads to lower quality
      of life. The aim of this study was to analyze the quality of life of patients
      with LBP after application of TENS (Transcutaneous Electrical Nervous
      Stimulation). MATERIAL AND METHODS: The study group included 30 computer workers
      (26 females and 4 males) aged 30-60 years (45 +/- 12). The quality of life was
      assessed using the World Health Organization Quality of Life instrument
      Abbreviated version (WHOQOL-Bref) before and after 10 applications of TENS.
      Outcomes were evaluated with a visual analog score (VAS) for pain and Schober's
      test to measure the ability of a patient to flex his or her lower back. RESULTS:
      The mean VAS value decreased significantly from 3.83 +/- 1.31 cm at baseline to
      3.36 +/- 1.21 cm after treatment. Patients reported pain relief. The highest
      quality of life scores in terms of social relationships were found in the social
      category evaluating personal relationships, social support and sexual activity
      (15.91 +/- 2.07) and mental health (14.32 +/- 1.59). After treatment a
      significant increase in the flexion of lower back was observed in the majority of
      patients. No significant correlations between the quality of life and the
      intensity of pain and the flexion of lower back before and after treatment were
      found. CONCLUSIONS: TENS therapy is an effective technique for pain relief in
      patients with LBP. TENS can also be used with other methods of LBP treatment and
      may improve the patients' quality of life.

PMID- 22880452
TI  - [Biological contamination in office buildings related to ventilation/air
      conditioning system].
AB  - BACKGROUND: Indoor air is contaminated with microorganisms coming from both the
      atmospheric air and sources present in premises. The aim of this study was to
      analyze the concentrations of biological agents in office buildings, dependending
      on ventilation/air conditioning system and season. MATERIALS AND METHODS: The
      study covered office buildings (different in the system of ventila-tion/air
      conditioning). Air samples for assessing the levels of inhalable dust, endotoxins
      and (1-->3)-beta-D-glucans, were taken at the selected stationary points of each
      building during summer and winter. The air was sampled for 6 h, using portable
      sets consisting of the GilAir 5 pump and the head filled with a filter of fiber
      glass. The samples for the presence of airborne bacteria and fungi were collected
      twice during the day using the impaction method. RESULTS: Average concentrations
      of inhalable dust, bacteria, fungi, endotoxins and (1-->3)-beta-D-glucans in
      office premises were 0.09 mg/m3, 6.00 x 10(2) cfu/m3, 4.59 x 10(1) cfu/m3, 0.42
      ng/m3 and 3.91 ng/m3, respectively. Higher concentrations of the investigated
      agents were found in summer. In premises with air conditioning concentrations of
      airborne fungi, (1-->3)-beta-D-glucans and inhalable dust were significantly
      lower in winter. In summer the trend was reverse except for (1-->3)-beta-D
      glucans. CONCLUSIONS: Concentrations of biological agents were affected by the
      season and the presence of air conditioning. Concentrations of inhalable dust,
      bacteria, fungi, endotoxins and (1-->3)-beta-D-glucans, observed inside the
      office buildings, were significantly higher in summer than in winter. The
      presence of the air conditioning system modified in various ways the levels of
      biological agents. Its influence was greater on the concentration of fungi and (1
      ->3)-beta-D-glucans than on that of bacteria and endotoxins.

PMID- 22880453
TI  - [Measures of occupational exposure to time-varying low frequency magnetic fields
      of non-uniform spatial distribution in the light of international guidelines and
      electrodynamic exposure effects in the human body].
AB  - INTRODUCTION: The aim of study was to analyze by computer simulations the
      electrodynamic effects of magnetic field (MF) on workers, to harmonize the
      principles of occupational hazards assessment with international guidelines.
      MATERIAL AND METHODS: Simulations involved 50 Hz MF of various spatial
      distributions, representing workers' exposure in enterprises. Homogeneous models
      of sigma = 0.2 S/m conductivity and dimensions of body parts - palm, head and
      trunk - were located at 50 cm ("hand-distance") or 5 cm (adjacent) from the
      source (circle conductor of 20 cm or 200 cm in diameter). Parameters of magnetic
      flux density (B(i)) affecting the models were the exposure measures, and the
      induced electric field strength (E(in)) was the measure of MF exposure effects.
      RESULTS: The ratio E(in)/B(i) in the analyzed cases ranged from 2.59 to 479
      (V/m)/T. The strongest correlation (p < 0.001) between B(i) and E(in) was found
      for parameters characterizing MF at the surface of body models. Parameters
      characterizing the averaged value of the field affecting models (measures of non
      uniform field exposure following ICNIRP guidelines), were less correlated with
      exposure effects (p < 0.005). E(in)(trunk)/E(in) (palm) estimated from E(in)
      calculations was 3.81-4.56 but estimated from parameters representing B(i)
      measurement accounted for 3.96-9.74. CONCLUSIONS: It is justified to accept 3.96
      9.74 times higher exposure to limb than that to trunk. This supports the
      regulation of labor law in Poland, which provides that the ceiling value for limb
      exposure to MF below 800 kHz is fivefold higher than that of the trunk. High
      uncertainty in assessing the effects of non-uniform fields exposure, resulting
      from a strong dependence of the E(in)/B(i) ratio on the conditions of exposure
      and its applied measures, requires special caution when defining the permissible
      MF levels and the principles of exposure assessment at workplace.

PMID- 22880454
TI  - [Analysis of methods for measurement and assessment of occupational exposure to
      electromagnetic fields in dielectric heating].
AB  - BACKGROUND: High-frequency (HF) welders are the most common devices that make use
      of dielectric heating. They are a source of high-intensity electromagnetic fields
      (EMFs). Manual operation of those welders makes that the limbs are exposed to
      EMFs of extremely high intensity, far in excess of the currently admissible
      values. The aim of this study was to update knowledge of actual exposure of HF
      welder operators to EMF and to optimize the procedure of exposure assessment.
      MATERIAL AND METHODS: Measurements of the EMF intensity in the vicinity of 10
      dielectric welders at work posts of 12 operators were performed. EMF measurements
      were made using the reference method, extended by auxiliary measurement points to
      measure induced currents I(L) in the limbs. Induced current measurements were
      performed in 20 operators tending the same HF welder. RESULTS: the highest values
      of the electric (E) and magnetic (H) fields measured at work posts were for whole
      body: E, up to 350 V/m, and H, up to 1.00 A/m; and for limbs: E, up to 600 V/m
      and H, up to 3.30 A/m. The W exposure indicator in the primary vertical
      measurement points was almost as high as 60. I(L) values measured at the wrist
      exceeded 64 mA and were individual-operator-dependent. CONCLUSIONS: EMF exposure
      of 25% of HF welder operators exceeded the national admissible values and after
      taking into account the operators' hands, this figure rose to 50%. The measured
      value of I(L), representing a measure of internal exposure to EMF, should serve
      as the main criterion in deciding whether working conditions are admissible.

PMID- 22880455
TI  - [Quality control testing of x-ray equipment used in medical diagnostic: results
      of interlaboratory comparison].
AB  - BACKGROUND: Effective diagnostic radiology system should be based on an efficient
      and suitable servicing of medical X-ray equipment. According to Polish
      requirements, all radiology departments are obligated to carry out quality
      control (QC) test of their X-ray set. In practice, testing is mostly performed by
      accredited external QC services, which have to participate in periodic
      interlaboratory comparison (ILC) to maintain or obtain the accreditation. Large
      scale ILC for QC services were performed at the Nofer Institute of Occupational
      Medicine for three ranges of diagnostic radiology: dental, conventional and
      mammography. MATERIALS AND METHODS: During ILC, the metrological coherence of
      main physical parameters, which determine good quality of diagnostic image, were
      estimated and compared with appropriate reference values ensured by ILC
      organizer. The ILC participants comprised 29 QC services. The measurements were
      performed by ILC participants under laboratory conditions, using their own
      calibrated meters, according to routine procedures. All measurement results were
      assessed by calculating the E(n) value, normalized with respect to the
      uncertainties. RESULTS: Of the 328 evaluated results only 11 (3.4%) were
      classified as unsatisfactory. As much as 82% of them applied to mammography.
      Thus, the final evaluation revealed negative results in 2 of the 29 participants,
      which means that their satisfactory scores for the studied ranges were below 75%.
      CONCLUSIONS: In spite of predominant amount of satisfactory results, ILC
      indicated some regions of divergence e.g. large differences in evaluation of
      uncertainties and other inconsistencies.

PMID- 22880456
TI  - [Polish adaptation of swing questionnaire (Survey Work-home Interaction -
      Nijmegen)].
AB  - The aim of the paper is to present the Polish adaptation of Survey Work-Home
      Interaction - Nijmegen (SWING). MATERIALS AND METHODS: The analyses were based on
      the survey results from two groups of subjects, a sample of workers,
      representative in terms of sex and age, living in urban areas (N = 600) and a
      group of 59 employees examined twice with a help of SWING to assess the stability
      of the obtained results over a month time. RESULTS: The analyses performed proved
      that the Polish version of SWING is a reliable tool for studying work-home
      interactions. Correlation coefficients of items with total result of negative
      work-home interaction (WHI) subscale varied from 0.51 to 0.74, with positive WHI
      subscale from 0.26 to 0.60, negative home-work interaction (HWI) subscale, from
      0.54 to 0.68 and positive HWI subscale from 0.31 to 0.59. Cronbach's alpha for
      the whole survey was 0.79, and for subscales varied from 0.73 to 0.89. The
      results of factorial analysis confirmed a our-factor structure of SWING. Factors
      I, items had loading from 0.58 to 0.81; II, from 0.29 to 0.78; III, from 0.60 to
      0.80; and IV, from 0.28 to 0.74. The values of fit index for a four-factor model,
      were 0.91 (NNFI), 0.06 (RMSEA), and 0.92 (CFI), which means that this model is
      characterized by a good fit to empirical data. The correlation coefficient
      between two measurements at one month interval were also high and reached the
      range of 0.63 to 0.84. CONCLUSIONS: The results obtained are comparable to the
      psychometric characteristic of the English version of SWING.

PMID- 22880457
TI  - [Exposure of healthcare personnel to ionizing radiation in the light of radiation
      hormesis hypothesis].
AB  - Radiation hormesis is a hypothetical premise that low doses of ionizing radiation
      (below 200 mSv) may be beneficial to living organisms. According to this
      hypothesis low doses of radiation stimulate the processes of DNA repair in cells.
      As a result they decrease the risk of aberration and the development of
      tumors.The theory of hormesis stands in contrast to the commonly accepted LNT
      hypothesis, which suggests that low doses of radiation exert only small but also
      negative effects on organisms. However, the effects of high doses of radiation on
      the human organism are well elucidated, the effect of low doses is still unclear.
      Low doses of radiation are received, among others, by the health-care personnel
      who are employed in areas that are affected by ionizing radiation. In Poland they
      receive average effective individual doses to the whole body exposure of around
      0.1-0.25 mSv per quarter of the year. Low doses of ionizing radiation, despite
      common views, may have a positive effect on health. However, one should approach
      this issue with some caution because of the current lack of sufficient and direct
      evidence that the theory of radiation hormesis is correct.

PMID- 22880458
TI  - [Simulator sickness as a valid issue of simulator-based research].
AB  - Simulators are increasingly being used in both research and training as well as
      in medicine, e.g., therapy of patients with diagnosed post traumatic stress
      disorders (PTSD). The use of simulators with strict control of environmental
      conditions allows for workload assessment or procedures improvement. Despite all
      the advantages of the utilization of simulators, the simulator sickness issue
      remains still topical. Simulator sickness may interfere with the measurement
      accuracy or effectiveness of training or therapy, but it can also be a source of
      stress for those carrying out the assignments on simulators. This article
      discusses problems associated with simulator sickness, paying particular
      attention to the scope of this phenomenon, its explaining theories and
      measurement methods.

PMID- 22880459
TI  - [Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico
      pathomorphological analysis of the cases and literature review].
AB  - OBJECTIVES: This retrospective study was designed to evaluate the clinical and
      pathological features and outcomes of patients diagnosed with uterine smooth
      muscle tumor of uncertain malignant potential (STUMP). MATERIAL AND METHODS: Ten
      patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the
      Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the
      institution databases. Variables of interest included histopathological details,
      age at diagnosis, types of treatment and recurrence rate. RESULTS: The mean age
      at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16
      months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm.
      Uterine bleeding was the second most frequent symptom observed in this cohort In
      three cases conservative procedure was performed, whereas in other patients
      hysterectomy was performed. No recurrence was observed during the follow-up
      period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or
      severe type, and in 3 cases necrosis was observed. In half of the tumors
      expression of TP53 was found, and value of MIB 1 was estimated at 2-35%.
      CONCLUSIONS: STUMP should be diagnosed by experienced pathologists due to the
      fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of
      these tumors allows to consider a conservative management in patients wishing to
      preserve fertility

PMID- 22880460
TI  - [The CHOICE study (Contraceptive Health Research Of Informed Choice Experience)-
      an educational research program for Polish women planning combined hormonal
      contraceptives use].
AB  - OBJECTIVES: The aim of the study was to develop an optimal educational model for
      contraceptive counseling, to analyze conditions influencing choice of hormonal
      contraception, to study patients' opinions on present, planned and proposed
      contraceptive methods and to link these data with socioeconomic and demographic
      conditions. MATERIALS AND METHODS: One thousand eight hundred fifty women (mean
      age 26.8 +/- 5.9 yrs) willing to use hormonal contraception were presented with
      essential information on combined hormonal contraception and asked to fill the
      anonymous questionnaire investigating factors influencing contraceptive choice
      and patients' opinion on alternative forms of birth regulation. The study was
      conducted in selected 185 centers in Poland and was a part of a larger survey
      (CHOICE) conducted on 11 216 women in Europe and Israel. RESULTS: Majority of the
      studied women were in stable relationship (85,5%), had higher or incomplete
      higher education (54.8%) and permanent job (54%). The purpose of the visit was to
      start/change contraception (64.2%), a routine gynecologic check-up (36.7%) or the
      need for a prescription for the continued contraceptive medication (18.7%). The
      most commonly used contraceptive methods were oral contraceptive pills (OCP
      38.7%) and condom (24.9%). Majority of women highly valued contraceptive
      counseling and more than 90% were eager to get familiarized with information
      leaflets. Before the counseling majority of subjects stated that were convinced
      to use OCP (52.7%; major advantages named: easy to use, favorable bleeding
      profile, amelioration of menstrual discomfort, comfortable, discrete) and
      contraceptive patch (22%; major advantages named: applied once a week,
      comfortable, simple, low risk for noncompliance, favorable bleeding profile).
      After the counseling there was an increase in proportion of women interested in
      contraceptive hormonal ring (by 19%; major advantages named: applied once a
      month, comfortable, very low risk for noncompliance, high efficacy and positive
      recommendation from a physician). In 58 women no hormonal contraception was
      recommended, predominantly due to medical contraindications. CONCLUSIONS:
      Appropriate patient counseling on all forms of combined hormonal contraception,
      with special attention paid to benefits and safety issues, suited to women's
      expectations and education is fundamental for the selection of an optimal birth
      control method.

PMID- 22880462
TI  - Relaparotomy after initial surgery in obstetric and gynecologic operations:
      analysis of 113 cases.
AB  - CONDENSATION: Even though relaparotomy is unavoidable in some cases, several
      measures such as careful surgical technique, meticulous hemostasis and aseptic
      conditions must be undertaken to prevent unnecessary interventions in obstetrics
      and gynecology OBJECTIVE: To assess the indications, procedures, risk factors and
      outcome for relaparotomy after obstetric and gynecological operations. STUDY
      DESIGN: A retrospective observational study during a four-year period in a
      tertiary care center was performed. Demographics such as age, parity and
      indications for relaparotomy as well as outcome measures in terms of
      complications and mortality rates were assessed in 113 patients who had undergone
      a relaparotomy after the initial obstetric or gynecological surgery RESULTS: The
      overall incidence of mortality after relaparotomy was 3.5%. Leading indications
      for the initial operation included placental abruption in 10 cases (8.8%),
      followed by the HELLP syndrome and previous cesarean section both in 5 cases
      (4.4%), and postpartum atonia in 4 (3.5%). The most common operations performed
      initially were cesarean section in 78 cases (69.0%) and 31 hysterectomies
      (27.5%). Principal indications for relaparotomy were bleeding and hematoma in 80
      cases (70.8%) and abscess in 10 cases (8.8%). The most frequently performed
      procedures at relaparotomy were drainage and resuturing of hematomas (n = 42,
      37.1%), hypogastric artery ligation (n = 32, 28.3%), hysterectomy (n = 31,
      27.5%), and drainage of abscess (n = 7, 6.2%). A second relaparotomy was
      performed in 4 cases (3.5%). Complications were encountered in 4 patients and 4
      cases ended up with mortality CONCLUSION: Hemorrhagic and infectious
      complications were the main indications for relaparotomy after obstetric and
      gynecologic surgeries. Cases with a history of placental abruption, HELLP
      Syndrome and previous cesarean section were under risk for relaparotomy. Despite
      favourable outcome, preventive measures such as careful surgical technique,
      meticulous hemostasis and aseptic conditions should be undertaken.

PMID- 22880461
TI  - [Evaluation of the intracellular expression of interleukin 17 in patients with
      ovarian cancer].
AB  - Knowledge of the role of interleukin 17 (IL-17) has led to the identification of
      new subpopulation of T helper lymphocytes--Th17 and T cytotoxic lymphocytes
      secreting IL-17 (Tc17). An increasing amount of attention is paid to their role
      in anti-tumor immunity. AIM: The aim of this study was to evaluate the percentage
      of peripheral blood, peritoneal fluid and cancer tissue CD4+ and CD8+ T
      lymphocytes producing IL-17 in patients with ovarian cancer MATERIAL AND METHODS:
      Forty patients operated due to advanced ovarian carcinoma and twenty-four
      patients with functional follicle ovarian cysts were recruited. Peripheral blood,
      peritoneal fluid and cancer tissue mononuclear cells from ovarian cancer patients
      were stimulated for 4 hours ex vivo with phorbol myristate acetate (PMA) (50 ng/
      ml) and ionomycin (1 microg/ml). The percentage of CD4+ and CD8+ T cells
      producing IL-17 was measured using flow cytometry. RESULTS: CD4+ and CD8+ T
      lymphocytes producing IL-17 were detected in the peripheral blood, peritoneal
      fluid and cancer tissue of ovarian cancer patients. The percentage of CD4+ T
      cells producing IL-17 was higher in the peripheral blood, peritoneal fluid and
      cancer tissue when compared to CD8+/IL 17+ T cells. The percentage of CD4+/ IL
      17+ was significantly higher in cancer tissue compared to T cells derived form
      peripheral blood. There was no difference in the percentage of CD4+/IL-17 + T
      cells between peripheral blood and peritoneal fluid and peritoneal fluid and
      cancer tissue of ovarian cancer patients. There was no difference in the
      percentage of CD8+/IL-17 + T lymphocytes in the peripheral blood, peritoneal
      fluid and cancer tissue in patients suffering from ovarian cancer. CONCLUSIONS:
      Increased percentage of CD4+/IL-17+ and CD8+/IL-17+ T cells in cancer tissue
      indicates that these cells are accumulated in ovarian cancer microenvironment.

PMID- 22880463
TI  - [Fungi isolated from the vagina and their susceptibility to antifungals].
AB  - INTRODUCTION: Because of the presence of various fungi and changes in their
      spectrum in the mycosis of vagina it is necessary to perform periodic overviews
      including testing their susceptibility to antifungal agents. OBJECTIVE: The
      objective of the study was to evaluate susceptibility of the fungi isolated from
      vaginas to antifungal drugs and to analyse the fungi responsible for vaginal
      mycosis in patients referred during a 7-year study MATERIALS AND METHODS: The
      study was carried out in a group of patients suspected of vaginal mycosis between
      January 1, 2005 and December 31, 2011. An analysis of the fungi isolated from
      their vaginas was performed. The susceptibility of the fungi to six antifungals
      (5-fluorocytosine, amphotericin B, miconazole, ketoconazole, itraconazole and
      fluconazole) was evaluated using a semiquantitative Fungitest. RESULTS: A total
      of 4775 mycological test results were evaluated. Fungi were present in 30.6% of
      the material. C. albicans was the most frequently isolated fungal species
      (80.2%), followed by C. glabrata (5.8%), and S. cerevisiae (5.5%). Itraconazole
      turned out to be the least effective drug. C. krusei. was the species most
      resistant to antifungals, including fluconazole. CONCLUSIONS: 1. C. albicans is
      the species most frequently isolated from a vagina. It is highly susceptible to
      azoles, the antimycotics generally used in the treatment of vaginal mycosis. 2.
      Out of the azoles under study ketoconazole was the most active against fungi in
      vitro while itraconazole was the least active. 3. The Candida non-albicans
      species, and particularly C. krusei, are less susceptible to antimycotics. 4.
      Amphotericin B and 5-fluorocytosine are most effective against Candida strains
      and S. cerevisiae, however they are not used in the treatment of vaginal mycosis
      because of their high toxicity

PMID- 22880464
TI  - [Expression of metalloproteinase MMP-9 and tissue inhibitor of metalloproteinase
      TIMP-2 in placenta of pregnant women with intrauterine growth restriction].
AB  - INTRODUCTION: The development of pregnancy depends on many factors, among other
      the implantation and the development of the placenta and placental vascularity
      The correct course of these processes depends on the proper activity of the
      enzymes degradating elements of extracellular matrix and basal membrane -
      metalloproteinases. OBJECTIVES: Assessment of the expression of MMP-9 and TIMP-2
      in the placenta of women with intrauterine fetal growth restriction. MATERIAL AND
      METHODS: Two study groups were distinguished - with untreated IUGR and with IUGR
      treated with the acetylsalicylic acid and L-arginine and the control group with
      correct fetal growth and course of pregnancy Marked microscope preparations from
      placental samples were made with specific antibodies for MMP-9 and TIMP-2.
      RESULTS: The greatest intensity of the reaction and the villous TIMP-2 expression
      was characteristic of the group with untreated IUGR. Strongest expression MMP-9
      was observed in the control group. The smallest surface of the trophoblast with
      positive MMP-9 reaction appeared in the group with untreated IUGR. CONCLUSIONS:
      High MMP-9 activity in the placenta correlates with its correct structure and
      function. Application of IUGR treatment reduces the expression of TIMP-2 in the
      placental villi.

PMID- 22880465
TI  - Periodontitis and risk of preterm birth and low birthweight--a meta-analysis.
AB  - INTRODUCTION: Periodontitis and prematurity are social diseases with common risk
      factors. In 1996 periodontitis was proven to be a possible significant and
      independent risk factor of preterm birth of newborns with low body weight.
      Numerous studies on the influence of periodontitis on the time of birth and/or
      birth weight of newborns have been conducted throughout the world since,
      including several ones in Poland, but their results have been inconsistent. Work
      objective: A meta-analysis of case-control, prospective and cohort studies on the
      influence of periodontitis on preterm birth and low birth weight. METHODS: The
      international and Polish bibliography bases were searched for essays on the
      relationship between periodontitis and preterm birth and/or low birth weight
      published between 1996 and 2010. All essays qualified for the meta-analysis were
      subjected to qualitative evaluation. The calculation of the overall odds ratio
      used both, fixed-effects and random-effects models (DerSimonian-Liard method).
      The heterogeneity of the included studies and effect of publication bias were
      also subjected to evaluation. RESULTS: The meta-analysis included 15 case-control
      studies, 1 cross-sectional study and 6 cohort studies. The essays came from 4
      continents: 8 from Europe (including 2 from Poland), 7 from South America, 4 from
      North America, and 3 from Asia. The total analysis covered 12047 pregnant women.
      The overall odds ratio of giving premature birth to a child with low weight for
      mothers with periodontitis in the model of random effects amounted to 2.35 (1.88
      2.93, p < 0.0001). For low birth weight, the overall OR was 1.5 (95% Cl: 1.26
      1.79, p = 0.001) for premature births--2.73 (95% CI: 2.06-3.6, p < 0.0001). A
      significant heterogeneity of the studies included in the meta-analysis was
      observed, and a significant publication bias was also demonstrated. CONCLUSIONS:
      The hypothesis of periodontitis as an independent risk factor of preterm birth
      and/or low birth weight needs further verification. In order to achieve that, it
      is necessary to conduct more methodologically well-planned cohort and
      intervention studies. The need of dental care for pregnant women as an integral
      component of the prenatal care program remains to be an important issue.

PMID- 22880466
TI  - [Ovarian cancer--modern approach to its origin and histogenesis].
AB  - Ovarian cancers (OC) belong to a heterogeneous group of pathologies and are
      traditionally classified with regard to histological type and degree of
      differentiation. OC was hypothesized to originate from ovarian surface epithelium
      (OSE) and inclusion cysts epithelium (IC). Unfortunately this theory was never
      supported by any clinical or molecular evidence linking carcinogenesis with OSE
      and was refuted. OC subtypes demonstrate morphologic features that resemble
      Mullerian duct-derived epithelia of the genital tract. Investigations of the HOX
      gene family Mullerian epithelial differentiation markers, confirmed the HOX genes
      expression in many subtypes of OC but not in OSE. The first step towards
      connecting OC origin with other than OSE genital tract structures were
      epidemiological observations indicating a minor OC risk after tubal ligation in
      women with the BRCA mutation. The first in situ carcinoma was found in the
      Fallopian tube fimbriae. Further research confirmed the same mechanism in
      sporadic OC. Endometriosis and endometrium cells may be a highly probable place
      of endometrioid OC initiation. Mucinous types share common futures with
      gastrointestinal tract cancers and there one needs to search for their
      precursors. Clear cell carcinoma may arise from glandular epithelium of
      endocervix or from endometrioid foci. The new classification of OC was proposed
      in 2004, suggesting to divide all OC into two types: I and II. Type II includes
      serous and endometrioid G3 subtypes, carcinosarcomas and undifferentiated OC.
      They are responsible for 75% of OC morbidity identified usually in FIGO stages
      Ill or IV, have poor prognosis and relapse early The remaining hystiotypes, with
      better prognosis and earlier FIGO stages at time of diagnosis, were classified as
      type I. Serous and endometrioid poorly differentiated ovarian cancers demonstrate
      mutation in TP53 gene (type II) and highly differentiated ones, generally in BRAS
      and KRAS genes (type I). The differences in molecular pathways also confirm
      different patterns of carcinogenesis of both OC types. Modern approach to OC
      histogenesis and origin emphasizes the necessity to verify OC screening,
      detection and treatment methods.

PMID- 22880467
TI  - Treatment of genital lichen sclerosus in women--review.
AB  - Lichen sclerosus is a chronic inflammatory skin disorder that belongs to a group
      of autoimmune connective tissue diseases, localized within the skin and mucous
      membrane of the anogenital area. In the latter location, the focal atrophy of the
      mucosa is the most visible sign. Lesions may be accompanied by symptoms such as
      itching, pain, burning. The disease occurs more often in females. The etiology is
      not fully understood. Genetic, infectious, hormonal factors and autoimmune
      mechanisms are taken into consideration. Early diagnosis and appropriate
      treatment is important to avoid further complications. This review aims to
      analyze available literature on the treatment of this disease entity

PMID- 22880468
TI  - [Optimization of antibiotic therapy in pregnancy--clinical implications].
AB  - The aim of the antibacterial therapy during pregnancy is to select a proper
      antibiotic and determine its effective dose, at the same time excluding the risk
      of potential teratogenic effect. Pregnancy is characterized by many
      physiological, disease-predisposing changes, particularly of bacterial etiology
      that have an influence on different pharmacokinetic of drugs. When determining an
      effective dose of an antibiotic, one should take into account changes in the
      pharmacokinetics (PK) of drugs in pregnant women, involving mainly the phase of
      distribution (increased volume of body fluids, cardiac output, reduced
      concentration of albumins), metabolism (induction of hepatic enzymes: CYP3A4,
      CYP2D6, CYP2C9, UGT1A4, UGT2B7, inhibition of CYP1A2, CYP2C19), and excretion
      (increased glomerular filtration rate). Results of few pharmacokinetic studies on
      pregnant patients point to the need of increasing the dose or reducing dosage
      intervals for some antibiotics (e.g. penicillin V ampicillin, piperacillin,
      imipenem, clindamycin). The aim of this study was to summarize current knowledge
      regarding the PK of antibiotics during pregnancy.

PMID- 22880469
TI  - Acute cortical blindness in preeclampsia--a case of reversible posterior
      encephalopathy syndrome.
AB  - BACKGROUND: Cortical blindness is one the most disturbing symptoms of reversible
      posterior encephalopathy syndrome in preeclamptic and eclamptic patients. The
      disease has been previously associated with a hypertensive breakthrough in the
      autoregulation of posterior cerebral arterioles followed by extravasation of the
      fluid into the brain tissue. CASE: 22-year-old primigravida in the 39th week of
      gestation diagnosed with gestational diabetes mellitus presented with mild
      preeclampsia and was admitted to our hospital. Antihypertensive treatment was
      initiated. Her blood pressure remained between 120/80 to 140/90 mm Hg. Glucose
      levels were within acceptable range. Before the labor induction she developed
      acute cortical blindness. Magnetic resonance imaging showed vasogenic edema
      localized in occipital lobes. Cesarean section was performed and anti-edematous
      treatment initiated. Blindness resolved by the fifth day postpartum. CONCLUSIONS:
      Reversible posterior encephalopathy developed in our patient in spite of
      normalized blood pressure that remained within autoregulation limits. Alternative
      pathogenesis and precipitating factors are discussed.

PMID- 22880470
TI  - [Polish Gynecological Society Ultrasound Section guidelines on ultrasound
      screening in gynecology (2 december 2011)].

PMID- 22880471
TI  - [The Polish Gynecological Society Expert Committee recomendations regarding
      application of fluconazole in the treatment of vulvovaginal candidiasis].

PMID- 22880472
TI  - Contribution of maternal-fetal adrenomedullin polymorphism to gestational
      hypertension and preedlampsia--gene-gene interaction pilot study.
AB  - INTRODUCTION: Adrenomedullin (ADM), a peptide with vasodilatory natriuretic and
      diuretic properties, is secreted in many tissues and shows multidirectional
      activity ADM activity may play an important role in the pathophysiology of
      gestational hypertension (GH) and preeclampsia (PE) by involvement in
      compensation of failed utero-placental unit circulation. AIM OF THE STUDY: The
      aim of the study was to evaluate the association of -1984A>G ADM gene
      polymorphism with the development of GH and PE in maternal-fetal dyads. MATERIALS
      AND METHODS: The study group consisted of 46 hypertensive pregnant subjects
      (further divided into two subgroups: 20 pregnant women with GH and 26 women with
      PE). 43 healthy pregnant women constituted the control group. The study and the
      control groups as well as the newborns were genotyped for -1984A>G ADM gene
      polymorphism using PCR/RLFP procedures. RESULTS: Minor--1984G allele was found to
      be higher in both, the GH (15.00%, OR = 3.62, p = 0.05), and the PE groups (9.62,
      OR = 2.18, p=ns) when compared with controls (4.65%). A tendency for higher
      frequency of minor -1984G allele (12.50 vs. 6.98% in controls, OR = 1.91, p=ns)
      was observed in the newborns from the GH group. It was also noteworthy that
      coexistence of both heterozygous genotypes of maternal-fetal dyads (-1984AG
      mother/1984AG fetus) was overrepresented in the GH group (15.00 vs. 6.98%, OR =
      2.35, p=ns) and in the PE group (11.54 vs. 6.98%, OR = 1.74, p=ns) when compared
      to controls. CONCLUSIONS: The observed tendency for overrepresentation of minor 
      1984G ADM allele in the GH and PE women and their newborns, despite lack of
      statistical significance, suggests participation of this genetic variant in the
      pathogenesis of the mentioned conditions. Additionally the obtained results could
      indicate that maternal-fetal gene-gene interaction may be a potential source of
      adverse perinatal outcomes.

PMID- 22880473
TI  - Retrospective analysis of placenta accreta: management strategies--evaluation of
      41 cases.
AB  - OBJECTIVE: The aim of the study was to evaluate maternal characteristics,
      surgical treatment options, and morbidity of patients with placenta accreta.
      METHODS: We retrospectively reviewed the medical records of placenta accreta
      patients who were diagnosed and hospitalized between 2006 and 2010 at the
      Obstetrics and Gynecology Clinics of the Dicle University Hospital (Center A) and
      Maternity Hospital (Center B) in Diyarbakir Turkey The data were retrieved from
      medical charts of both hospitals. Maternal demographic features, clinical
      outcomes, type of surgical intervention, and complications were evaluated.
      RESULTS: The incidence of placenta accreta was 1/426 deliveries in Center A and
      1/7573 deliveries in Center B over a 5-year period. Thirty-nine (95.1%) patients
      had placenta previa, and 32 (78.0%) patients had at least one previous cesarean
      delivery Hysterectomy was performed in 28 (68.3%) of 41 women with placenta
      accreta and uterine preservation was achieved in 13 (31.7%) of them. One (2.4%)
      maternal death occurred. Estimated blood loss was >2 liters and all patients
      required blood products transfusion. CONCLUSION: Placenta accreta is highly
      associated with the existence of placenta previa, especially in cases with
      previous cesarean delivery When placenta accreta is diagnosed or suspected, the
      patient should be referred to a tertiary center for optimum care, where the
      obstetrical team should include experienced pelvic surgeons who are capable of
      performing emergent hysterectomy internal iliac artery ligation, and uterine
      devascularization procedures.

PMID- 22880474
TI  - [Long-term outcome analysis in the treatment of granulosa cell tumors].
AB  - INTRODUCTION: Granulosa cell tumors of the ovary (GCT) are derived from the sex
      cords and the ovarian stroma. Their natural history however is indolent with a
      very favorable long-term prognosis. Their extreme rarity represents a limitation
      in our understanding of their natural history management, and prognosis. MATERIAL
      AND METHODS: Retrospective analysis of patient documentation treated for GCT
      between 1988-2008 at the Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw,
      was performed. Clinical and pathological features of the study group, as well as
      methods and results of the treatment were analyzed. RESULTS: Medical
      documentation of 148 patients was analyzed. The majority of patients was
      classified as FIGO stage 1 (87.5%). Surgery was performed as primary treatment in
      all cases. Forty eight patients (32,6%) were held for observation stays, whereas
      57.1% were qualified to receive adjuvant treatment: chemo- or radiotherapy. Mean
      progression free survival was 133.5 months (11.1 years) and was significantly
      longer in patients treated with the chemotherapy regimen when compared to
      radiotherapy (148 vs. 91 months respectively; p = 0.028). Overall survival was
      173,7 months and was significantly longer in patients treated with adjuvant
      chemotherapy vs. RTH (165 vs. 121 months; p = 0.068). Recurrence of the disease
      was associated with poorer prognosis. CONCLUSIONS: GCTs are potentially curable
      neoplasms of the ovary with low treatment failure rates. Quick diagnosis and
      appropriate treatment in centers experienced in ovarian cancer surgery are the
      necessary conditions to obtain good results. The stage of the disease remains the
      most important prognostic factor chemotherapy with the use of bleomycine
      etoposide and cisplatin should be considered in patients who require adjuvant
      treatment.

PMID- 22880475
TI  - Influence of social competence of physicians on patient compliance with
      osteoporosis medications--a study on Polish postmenopausal women.
AB  - OBJECTIVE: The aim of the study was to examine the impact of social competence of
      physicians on the effectiveness of patient compliance and persistence with
      therapy. MATERIAL AND METHODS: The study included physicians and their patients,
      previously diagnosed with osteoporosis, and eligible to receive pharmacological
      treatment. The physicians were evaluated with the social competence questionnaire
      involving three dimensions: social exposure, intimacy and assertiveness, as well
      as in the combined scale. All patients in the study group were prescribed the
      same medication: alendronate once a week. Compliance and persistence of the
      patients were juxtaposed with social interaction skills of physicians during 7
      scheduled appointments at 2-month intervals. RESULTS: Doctor's effectiveness in
      situations demanding close interpersonal contact was higher in the group with
      good compliance--group A (p < 0.001), as well as in the situations of social
      exposure, (p < 0.001). On the other hand, their assertiveness was higher in the
      group with poor compliance--group B (p < 0.001). Co-morbid conditions (group A:
      76%, group B: 74%), as well as earlier fractures (40.43% vs. 36.78%) were
      comparable in both groups. Disease acceptance and suggested methods of treatment
      were more often accepted by patients from group A than group B (56% vs. 33%,
      respectively). CONCLUSIONS: (1) Disease acceptance is essential for effective
      treatment. (2) Social skills of physicians influence patient adherence to therapy
      recommendations. (3) Close interpersonal contact between physicians and their
      patients eliminates the feeling of fear and

PMID- 22880476
TI  - [Prevalence of uterine malformations and their impact on fertility].
AB  - AIM: Uterine malformations belong to the most common congenital abnormalities
      within the female reproductive system. Their mean prevalence in the general
      population is 2-4%. The incidence of uterine malformation leads to impaired
      fertility and a number of obstetric complications such as threatening preterm
      delivery pelvic and transverse presentation, premature departure of amniotic
      fluid, intrauterine growth restriction, threatening rupture of the uterus,
      caesarean section. The aim of this review is to analyze the influence of an
      individual uterine malformation on female fertility. MATERIAL AND METHODS: The
      study involved 124 women hospitalized at Research Institute of the Polish Mothers
      Memorial Hospital in Lodz between the years 1994-2007. The patients were divided
      into 6 groups on the basis of the diagnosed defect. RESULTS AND CONCLUSION: In
      our study the most common defect was uterus bicornis, diagnosed in 46.7% of
      cases. The worst obstetric outcome was found among patients with septate uterus.
      The highest number of miscarriages and fertility problems occurs among those
      women. Nevertheless, there are positive data on the treatment of this defect. It
      would be recommendable to extend the diagnosis of the uterine malformations,
      especially in women with fertility problems, because early diagnosis and
      appropriate treatment allow to obtain satisfactory obstetric outcomes.

PMID- 22880477
TI  - Efects of hormone replacement and tamoxifen on depression in ovariectomized rats.
AB  - OBJECTIVES: To determine the effects of tamoxifen and hormone replacement therapy
      in order to assess their role in depressive behavior: MATERIAL AND METHODS:
      Different protocols of hormone replacement therapies were administered to
      surgically ovariectomized rats. Intact rats were used for tamoxifen experiments.
      Properly assigned control groups were used and cognitive processes were studied
      on animal models of surgical menopause using the Porsolt forced swim test and
      locomotor activity experiments. RESULTS: In the tamoxifen experiments, an
      interaction between treatment and days did not reach statistical significance,
      but indicated a trend in this direction [F(1,26)=3.557, p = 0.071]. The number of
      repeated movements significantly decreased after the Porsolt test (F(1,44) =
      8.483, P < 0.006) in the hormone replacement experiments. In the tamoxifen
      experiments, the number of repeated movements significantly decreased after the
      Porsolt test (F(1,26) = 74.410, P < 0.001). CONCLUSIONS: While sequential hormone
      replacement is found to be protective against depression, tamoxifen seems to
      augment behavioral despair

PMID- 22880478
TI  - [Recurrent cervical cancer--therapeutic options].
AB  - Cervical cancer is a malignancy associated with high morbidity and mortality in
      Poland. In a high number of cases the disease is diagnosed at an advanced stage,
      namely FIGO IB2-IVA. The standard method for radical treatment in these patients
      is external beam irradiation, together with concurrent chemotherapy based on
      cisplatin in the first stage, and brachytherapy in the next step. Despite such
      radical treatment, nearly half of women have relapses within the genital tract
      and regional lymph nodes. The procedure in these patients is a difficult
      therapeutic problem in gynecologic oncology There is a small percentage of
      relapses, which are located exclusively in the genital tract. In these cases
      appropriate treatment offers a chance for permanent cure, but also a high risk of
      lower quality of life, which is the consequence of surgery or radiotherapy
      Therapeutic options available in this strictly selected group of patients are the
      subject of the present analysis.

PMID- 22880479
TI  - [Nerve growth factor as a biomarker in the diagnosis and treatment of overactive
      bladder (OAB)].
AB  - Nerve growth factor is a complex regulator of neural plasticity along the
      micturition pathways. The aim of this review is to summarize the current evidence
      for a role of NGF in urinary bladder function both in experimental and clinical
      settings. There is bulk of strong evidence that experimental administration of
      NGF elicits the symptoms of increased sensation, urgency and bladder
      hyperreflexia which strongly resemble overactive bladder syndrome (OAB) and
      interstitial cystitis/painful bladder syndrome (IC/PBS). Therefore in human
      studies there are attempts to employ urinary NGF levels as a diagnostic marker in
      various forms of OAB and IC/PBS. It has been shown that urinary NGF levels are
      correlated with severity of OAB symptoms and in patients successfully treated
      with antimuscarinics agents or detrusor botulinum toxin injection, urinary NGF
      levels decrease significantly in association with reduction of urgency severity

PMID- 22880480
TI  - Survivin--prognostic tumor biomarker in human neoplasms--review.
AB  - Accurate diagnosis and proper monitoring of cancer patients remain important
      obstacles for successful cancer treatment. The search for cancer biomarkers is
      carried out in order to quickly identify tumor cells and predict treatment
      response, ultimately leading to a favorable therapeutic outcome. One such
      prognostic marker seems to be survivin. Many studies have shown that survivin is
      strongly expressed in a vast majority of cancers. Its overexpression was
      demonstrated in breast and lung cancer prostate, gastric, colon, bladder and
      esophageal carcinomas, osteosarcomas, and lymphomas. In many of those tumors,
      high activity of the surviving gene was associated with a poor prognosis and
      worse survival rates. Moreover survivin expression was correlated with resistance
      to chemotherapy and radiotherapy-induced apoptosis. Since survivin may be
      identified as an independent prognostic factor and inhibitor of apoptosis, it may
      prove to be a useful therapeutic target in cancer therapy

PMID- 22880481
TI  - [Jaundice as the first symptom of HELLP syndrome--case report].
AB  - Jaundice is a rare symptom of the HELLP syndrome (hemolysis, elevated liver
      enzymes, low platelet count) and is diagnosed in only 5% of the patients with
      this condition. However jaundice is related with sever presentation of the
      disease and associated with higher mortality The aim of this paper was to present
      a case of 24-year-old patient with jaundice as the first symptom of severe HELLP
      syndrome. A review of the literature about symptoms and treatment of HELLP
      syndrome and differential diagnosis of jaundice in pregnancy was done as well.

PMID- 22880482
TI  - [Aortic coarctation in the recipient in TTTS--diagnostic problems--a case
      report].
AB  - The paper presents a case of coexistence of the aortic coarctation with TTTS.
      This rare coincidence and hemodynamic disturbances resulting from hypovolemia
      interfere with the hemodynamic picture of the structural cardiac defect. Prenatal
      diagnosis is based on the assessment of the size of both ventricles. If the
      defect is present, the left ventricle is usually smaller than the right one.
      Coarctation may be also suspected in case there is disparity between large
      vessels in the mediastinum. Comparison of the width of the aorta, and ductus
      arteriosus, especially if the rate is 2:1 in favor of the latter may suggest such
      defect. Furthermore, the finding of continuous flow through the aortic isthmus
      increases the likelihood of the defect 16-fold. The presence of "coarctation
      shelf" in color Doppler may suggest the existence of the cardiac defect that will
      require an intervention. In the present study the aortic coarctation was
      diagnosed in the recipient, who presented marked features of hypervolemia in
      venous Doppler studies, and in echocardiographic assessment of the right heart.
      The paper presents signs of hemodynamic disturbances in Doppler studies and
      changes of Doppler blood flow parameters observed during therapy (i.e.,
      amnioreduction, fetoscopy). Diagnosis of coarctation may be hindered by the
      presence of the right heart volume overload, hypertrophy of the heart muscle as a
      result of associated hemodynamic disturbances in twin-to-twin transfusion
      syndrome. The impact of therapeutic interventions such as amnioreduction and
      fetoscopy the on cardiovascular hemodynamic parameters of both fetuses is also
      discussed. Also, a wide ductus arteriosus may make it difficult to diagnose this
      defect in utero. The paper presents diagnostic and therapeutic management in a
      case of TITS complicated by an aortic coarctation in the recipient.

PMID- 22880483
TI  - [Features of pubescence in patients with pure gonadal dysgenesis in the course of
      a hormonally active tumor--case report].
AB  - Germ cell tumors are the most frequent ovarian neoplasms among girls and young
      women under the age of 25. Female patients with gonadal dysgenesis are at higher
      risk of germ cell tumors. Two cases of women with pure gonadal dysgenesis were
      described. A hormonally active tumor secreting estrogens, caused the development
      of sexual features and genital tract bleeding what imitated premature puberty. It
      needs to be emphasized that the presence of sexual features does not exclude
      dysgenesis - a pathology that is connected with an increased risk of gonadal
      tumors--and that the ultrasound evaluation, during which the presence of
      follicles in gonads is evaluated, is essential.

PMID- 22880484
TI  - Rare case of uterine PEC-oma (perivascular epithelioid cell tumor) recurrence.
      Case report and literature review.
AB  - Perivascular epithelioid cell tumor (PEC-oma) is a rare mesenchymal neoplasm.
      Literature reports more than 100 cases of PEC-oma, a third of which is of uterine
      or uterine retroperitoneum origin. The case of a 59-year-old woman presented here
      is, to the best of our knowledge, the first described fast uterine PEC-oma
      recurrence of the tumor of the gastrointestinal tract origin. In this text the
      authors also present literature review concerning this rare female tumor

PMID- 22880485
TI  - [Selective progesterone receptor modulatores for uterine fibroid treatment--the
      statement of the Polish Gynecological Society experts].

PMID- 22880486
TI  - The hygienist and sociologist Louis-Rene Villerme (1782-1863): a pioneer of
      occupational medicine.
AB  - BACKGROUND: Louis-Rene Villerme's work and research have ranked him among the
      most important figures in the history of occupational medicine. OBJECTIVES: The
      aims of this article were to objectively record the influence and the impact of
      Villerme's life and work on the establishment of occupational medicine. METHODS:
      A thorough analysis of scientific and historical literature on the subject was
      conducted. The authors paid special attention to primary French sources. RESULTS:
      Louis-Rene Villerme was born in Paris in 10 March 1782. Taking advantage of his
      good fortune and financial prosperity, due to the recognition of his initial
      work, he progressed efficiently and with decision towards a new way of thinking.
      He stressed the importance of observation of the social environment, the role of
      investigations on lack of hygiene, the significance of statistical recording and
      the study of demographic statistics, and devoted himself to the labour force's
      health problems. He died in his homestead on 16 November 1863. CONCLUSIONS:
      Villerme lived an intense life full of activity, social work and travel. His
      support of the working classes' rights, his opposition to child labour and gender
      inequality, and his fight for humane conditions in prisons remain diachronic
      ideals. He provided a reference model for socio-medical research and contributed
      to the establishment of the new scientific discipline, Occupational Medicine.

PMID- 22880487
TI  - [Discrimination at the workplace among immigrants in Italy].
AB  - BACKGROUND: Discrimination at the workplace can be considered a risk factor for
      immigrants' health. OBJECTIVES: In this study we compared the occurrence of
      episodes of arrogance or discrimination perceived at the workplace between
      documented immigrants coming from countries with high migration pressure and
      Italians, and evaluated the role of selected risk factors among immigrants.
      METHODS: Using data from the 2007 Labour Force Survey conducted by the Italian
      National Institute of Statistics, adjusted odds ratios (ORs) for socio
      demographic and occupational variables were estimated among a nationally
      representative sample of 61,214 employed persons aged 15 years or more. RESULTS:
      The occurrence of perceived arrogance or discrimination was higher among
      immigrant compared to Italian males for all geographical areas of origin
      considered. Adjusted ORs were 4.6 (95% CI: 3.6-5.8) for Africans, 3.4 (95% CI:
      2.5-4.6) for Asians, 2.1 (95% CI :1.6-2.8) for Eastern Europeans, and 2.0 (95%
      CI: 1.0-3.7) for Latin Americans. Among male immigrants a higher occurrence of
      arrogance or discrimination was found for construction and other industrial
      workers and for those residing in central-southern regions of Italy. Among female
      workers only Latin Americans and Africans showed a higher occurrence of perceived
      arrogance or discrimination compared to Italians: adjusted ORs were respectively
      3.9 (95% CI: 2.6-5.7) and 2.6 (95% CI:1.5-4.5). Female immigrants with a medium
      to-high level of education or a highly skilled job, and those residing in the
      central-southern regions of ltaly perceived the highest occurrence of arrogance
      or discrimination. CONCLUSIONS: The study highlighted the need for policies to
      protect the wellbeing of immigrants that seem to be particularly exposed to
      patterns of discrimination at the workplace.

PMID- 22880488
TI  - Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso
      population 17 years after the accident.
AB  - BACKGROUND: The Seveso accident (Italy) in 1976 caused the contamination of a
      large population by 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3, 7,8-TCDD). The
      contaminated territory was divided into three zones: A (very high contamination),
      B (high contamination), and R (low contamination). We report here the plasma
      concentrations of seven polychlorinated dibenzo-para-dioxins (PCDDs), 10
      polychlorinated dibenzofurans (PCDFs), four non-ortho-polychlorinated biphenyls
      PCBs (nPCBs), and Toxic Equivalencies (TEQs) in a sample of residents in the most
      polluted zones A and B and in a reference non-contaminated zone. METHODS: From
      December 1992 to March 1994, 62 individuals were randomly selected from the
      population living in zone A (No. =7) and B (No. =55). A sample of 59 subjects
      living in a surrounding non-contaminated area (non-ABR), frequency-matched by
      gender, age, and smoking history, was used as reference. All subjects were
      administered a questionnaire surveying demographic, lifestyle, medical history,
      and accident-related factors. We assayed plasma PCDD, PCDF, and nPCB
      concentrations by high-resolution gas chromatography/high resolution mass
      spectrometric (HRGC/HRMS) analysis, with results reported as pg/g of lipid, or
      parts per trillion (ppt). We calculated TEQs using the WHO 2005 Toxic Equivalency
      Factors (TEFs). RESULTS: We found elevated median levels of 2,3, 7,8-TCDD in
      plasma samples of subjects living in zone A (73.3 ppt) and zone B (12.4 ppt),
      compared with residents in the reference zone (5.5 ppt). In analyses adjusted for
      gender, age, smoking, and body mass index (BMI), none of the other congeners
      showed levels higher than reference in the contaminated zones. Compared with men,
      women showed higher levels (113%) of 2,3, 7,8-TCDD and a slight elevation (17%)
      of TEQ for the other congeners. Age was strongly positively associated with most
      congener levels; TEQs for PCDDs, PCDFs, and nPCBs showed respectively 12%, 24%,
      and 41% increases for every 10 years of age. Current smokers had lower (from -37%
      to -67%) TEQ levels than subjects who had never smoked. BMI was negatively
      associated with levels of a few congeners, but with no impact on TEQ values.
      CONCLUSIONS: The Seveso accident caused a severe exposure of the population to
      2,3,7,8-TCDD only. None of the other congeners analyzed showed variation across
      zones. Age showed a strong positive association with TEQs for all classes of
      compounds (PCDDs, PCDFs, and nPCBs).

PMID- 22880489
TI  - [Workplace safety in private companies of freights and on the road workers:
      comparison between small and medium enterprises].
AB  - BACKGROUND: The road freight and passenger transport sector exposes the workers
      of this sector to a considerable health risk. Application of the relative
      legislation to safeguard worker's safety is an obligation for the employer.
      OBJECTIVES: The aim of the study was to assess the application of current
      legislation in the trucking sector and ascertain whether there are differences
      between large and small enterprises. METHODS: The study was conducted through
      direct interview with managers of road freight and passenger transport companies
      in the Lazio Region in 2009. Information was collected using a questionnaire
      composed of 77 items concerning risk assessment and organization aspects in the
      enterprises. The enterprisers were stratified by number of workers and drivers.
      To detect possible associations the Chi-squared and Fisher's Exact tests were
      used. RESULTS: A total of 42 enterprisers participated in the study. Significant
      differences were found between larger enterprisers (10 workers) and smaller
      enterprises (< 10 workers), concerning risk assessment from vibrations (p =
      0.006), night work (p = 0.026), microclimatic conditions (p = 0.047). Regarding
      risk prevention/management aspects, the enterprisers with a higher number of
      workers were more likely to have a workers' representative for safety compared to
      the smaller enterprises (respectively 88.9% versus 50.0%) and a road accidents
      Register (77.8% versus 16.7%), with p < 0.001 significance levels. CONCLUSIONS:
      The risks most frequently assessed, in decreasing order, were: vibrations, manual
      handling of loads, stress, noise, awkward postures, night work, alcohol
      consumption, drug addiction and microclimatic conditions. Vibrations, night work
      and microclimatic conditions risks were assessed to a lower degree in the smaller
      enterprisers compared to the larger enterprises.

PMID- 22880490
TI  - [Work-family conflict in call center].
AB  - The working environment of call centers, which have seen a significant growth in
      recent years, has been the subject of several studies aiming at understanding its
      specific dynamics, with particular attention to the possible causes of stress and
      discomfort. Despite the fact that the work-family conflict is considered a source
      of stress responsible for undermining workers' well-being, and as such has been
      explored in many work environments, there is still very little research specific
      to call centers. OBJECTIVES: This study had the following aims: to explore work
      family conflict perceived by call-center operators taking account of any
      differences related to respondents'professional and personal characteristics; to
      understand which demands and resources can have an impact on work-family conflict
      in this context. METHODS: The study was carried out on a sample of 898 call
      center operators in a telecommunications company through the administration of a
      self-reporting questionnaire. Data analysis included: t-test, one-way analysis of
      variance, linear correlations and multiple regressions. RESULTS: A higher
      perception of work-family conflict among workers having a full-time contract was
      observed compared to those having part-time contracts. Multiple regression
      analysis identified as sources of influence on work-family conflict: emotional
      dissonance, uneasiness due customer dissatisfaction, workload, avoidance coping
      and working hours. CONCLUSIONS: Work-family conflict in the context studied is
      not particularly critical: it is in part influenced by professional and personal
      characteristics of respondents and primarily caused by work demands. Managerial
      implications are discussed, especially referred to training activities.

PMID- 22880491
TI  - [A new scale for measuring the psycho-physical effects of work-related stress in
      a perspective of methods integration].
AB  - BACKGROUND: This study fits into a perspective of integrated work-related stress
      assessment, in response to the need to limit the common method variance and the
      role played by individual variables in subjective measures. OBJECTIVES: The goal
      of this study was to check the metric properties of a new scale of mental and
      physical strain developed for the evaluation of stress symptoms by the physician
      and to detect the antecedents of psycho-physical symptoms, in terms of both
      individual and work characteristics, through an integrated approach. METHOD: The
      study was conducted on 409 workers involved in health surveillance activities, to
      whom the new scale and a subjective assessment tool were administered. RESULTS:
      Confirmatory factor analysis showed that the scale is a reliable tool for hetero
      evaluation of psycho-physical symptoms attributable to stress at work. Moreover,
      specific individual characteristics, such as the presence of prior health
      disorders and the female gender, and organizational features, such as the
      pathological work/life conflict and the workload, were found to be risk factors
      in relation to psychological and physical strain. Age, consumption of alcoholic
      beverages between meals, relationships with colleagues, and the characteristics
      of the workplace were instead found to be important protective factors.
      DISCUSSION: The adoption of an integrated approach made it possible to improve
      and study in depth the ways of work-related stress assessment, highlighting the
      pivotal role of the occupational health physician making the evaluation.

PMID- 22880492
TI  - [Not Available].

PMID- 22880493
TI  - [Know the past, understand the present, and anticipate the future].

PMID- 22880494
TI  - [Health and politics in France].
AB  - Health is a dual notion. It is individual, singular and intimate. It is also
      collective, statistical and political. The modern problematic of health relies
      upon a balance of complex relations between individual and collective acceptances
      of the notion. You can try to outline the evolutions and the main concepts
      through a quadruple approach: health and politics, health and its professionals,
      health and society and in the end, health and the State. The relationships
      between health and politics in France are affected by the historical delay of
      France in public health, namely because of a structural weakness of the
      administrative organization of public health. Nevertheless France developed a
      dense and well organized care system and a universal social protection against
      the disease. The creation of the health professions in France was marked by a
      historical opposition between the doctors and the state which led to a failure of
      hygienist medicine and a fundamental misunderstanding on health insurance.
      Medical domination led to the organization of a system based on professional
      dichotomy and the delegation of the regulation skills to the health care
      professionals. The role of health issues in the French society was deeply renewed
      by the development of the medical and epidemiological knowledge. This resulted in
      a new political responsibility in the management of health risks but also in the
      confirmation of the patients' rights and the role of their associations in the
      health systems operations and the piloting of public policies. In this
      environment, the state has recently and progressively confirmed its dominating
      role in the health sector. A public hospital service was created In the 60's and
      70's, then in the 80's there were recurrent interventions in order to control
      health spendings and eventually in the 90's health safety devices were set up.
      More recently, a process of health policies institutionalization confirmed this
      evolution. In the future, health issues should be regarded as priorities for
      public actions because of social and humanitarian challenges they represent, but
      also the new political and bioethical questions they give rise to.

PMID- 22880495
TI  - [Looking over the progress of care. Historical and ethical aspects of the
      relations between health professionals and patients].
AB  - If the idea of care materializes by a friendly behaviour, word or movement, the
      characters who implemented it have seemed, over the history, motivated by varied
      ideals. Certainly, their name, status and role have not always been precisely
      described; but their intervention happens to be bound to moral and scientific
      requirements enriched by collective representations. So after the nobility
      welcome of the wandering, impoverished and sick stranger, related by Homeric and
      biblical narratives, the more or less protected professional organization has
      appeared on behalf of the Greek city, then the Roman one. The image of the
      suffering Christ has then imposed itself where the distress of the patient could
      be read; it constituted the engine of the charity due to the latter, whose
      demonstrations proliferated in the Middle Ages. However, because of the necessary
      disease prevention in front of epidemics which stressed the increasing
      opportunities of war and travel, a more and more complex institutional
      organization has established itself little by little bound to technical and
      political considerations. More precisely, in the last two centuries, the social
      unrest bearing aspiration to public health and people's safety has underlied
      Republican ideals of freedom, solidarity and individual expression. This is what
      the Nursing staff duty - officially recognized as "healthcare professionals" -
      responds to today to ensure favorable conditions to the dawn of feelings of
      comfort, self-fulfillment and respect. As much by caring and listening they
      ensure as by technical acts they operate, they in fact, participate in the
      implementation of a distribution of common wealth. Health and welcome of the most
      deprived therefore constitute, thanks to their thoughtful intervention, the
      stammerings of a policy of active citizenship.

PMID- 22880496
TI  - [Object of research, methods and sources in history].
AB  - History is the oldest Social Sciences. Its approaches are often empirical but may
      be borrowed from other disciplines, and its concepts may have been elaborated by
      philosophers. Nevertheless, it requires a great rigour in the study of sources,
      notably by an external and an internal criticism. Thanks to very rich archives
      (particularly the hospital collection), it is possible to write the history of
      nurses.

PMID- 22880497
TI  - [For a critical history of the concept of anxiety].
AB  - Anxiety, tension, anguish... These are words, but first of all, states of the
      self. Accepted since the dawn of time by human distress and by the effort to
      understand them, they were taken back in hand by Psychopathology, established as
      a little dark concepts, and as such have become today so sovereign in the most
      ordinary way that their "reality" seems to be obvious. This recent
      acknowledgement is however the result of a history. To attempt to restore the
      original bases enables to find in it the old and well-thought-out acknowledgement
      in a common nature, the unknown factors of which were considered for a long time
      with familiarity and distance by common people as well as by doctors. This
      unconventional look, that we suggest to have here over a long period of time,
      allows us to restore, in the outermost bounds of Psychosomatics, all the
      ambiguities of a present notion which was at first physiological before appearing
      in psychiatric Nosology. It also means to take a certain distance from the
      medicalization of affects which, whatever we think, naturally come from our
      mortal condition.

PMID- 22880498
TI  - [History and testimonies of visiting nurses (1905-1938)].
AB  - Although short-lived, the history of visiting nurses is rich in political, social
      and health consequences it has generated. It involves the establishment of a new
      know-how in the first part of the twentieth century, mostly social, by the fact
      that the nurse comes out of the hospital to go and visit families in need. How
      this profession has been built and what is the impact of its social intervention
      on the population before the Second World War? Based on contemporary studies,
      institutional archives and biographical works, this study considers an immersion
      in the heart of the visiting nurse profession, through unwavering dedication,
      female emancipation and unexpected misery.

PMID- 22880499
TI  - [Fundamental research in nursing sciences. Historical research on the foundations
      of a discipline].
AB  - For lack of serious fundamental research in History on the standardization of its
      own discipline, the nursing profession continues to be fed by cliches, common
      sense, and relies on symbols and faiths stemming from the past as well as on what
      characterizes in a general way the female careers in our society. The lack of
      recognition experienced by the nursing profession is not so surprising from then
      on. At the time of the globalization of knowledge, which remains to this day, the
      only source of sustainable competitive advantage, the historian of the nursing
      discipline should start wondering about the international status of his
      discipline within the learned worlds.

PMID- 22880500
TI  - [Nurses, teachers and pioneers: the students and permanent teaching staff at the
      opening of International School of Nursing in Lyon in 1965].
AB  - On the initiative of the World health organization, the international School of
      nursing university education opens in Lyon on September the 6th, 1965 and closes
      30 years later. After having approached the national and international context of
      this creation, the study, based on archives and contemporary printed sources and
      various interviews of living witnesses, boarding and teaching, only-female staff
      present at the opening of the School, shows that it's all about pioneers and
      activists to the nursing cause, each of them doing it her own way. The
      background, the training, the personality, the educational choices and the
      publications of most of them give evidence of their will to contribute actively
      to the development and valuation of nursing as a discipline without naming it, by
      being inspired by foreign experiences well ahead of the french situation at the
      time. Good intentions to confront with the complex reality of the stakes and
      games of the numerous actors involved in those years realization.

PMID- 22880501
TI  - [Leonie Chaptal (1873-1937), architect of the nursing profession].
AB  - Leonie Chaptal was a wealthy heiress. She had an excellent education that she
      completed on her own initiative. Between 30 and 40 years old, she founded and
      managed health charities in a popular and disadvantaged district of Paris. She
      was interested in all the aspects of life, from birth to death. Though fervent,
      she lived as an officially laic liberal catholic woman. Her noticeable competency
      brought her to sit at the Conseil superieur de l'Assistance publique (Welfare
      services), where some national decisions of public health were made. Her action
      against tuberculosis was acknowledged worldwide. She opened a training school in
      nursing care from 1905, and participated to the national and international
      debates on this theme of training. During the Great War, she was particularly
      active. In the 1920s, she presented a report on nursing education which
      immediately gave rise to the drafting of a decree which structured nursing
      schools and programs in France, as well as the obtaining of a nursing diploma
      after two years of studies at school. But to practice, this diploma was not
      required, what depreciated the function. After having created the French
      association ANIDEF, she became the president of the International Council of
      Nurses. Between the wars, the practice of the nursing profession was far below
      Leonie's aspiration, who was torn between her opponents: some Republicans little
      likely to favour women's work and some Catholics attached to claim their faith.

PMID- 22880502
TI  - Paraganglioma of the cavernous sinus.

PMID- 22880503
TI  - Intrapelvic hibernoma: an incidental finding.

PMID- 22880504
TI  - Alcoholic pancreatitis and midgut malrotation.

PMID- 22880505
TI  - Small bowel infarction due to mesenteric venous thrombosis.

PMID- 22880506
TI  - Fibroadenoma of the breast with positive pet-scan.

PMID- 22880507
TI  - Aneurysm of aberrant right subclavian artery.

PMID- 22880508
TI  - Acute cholecystitis with pseudoaneurysm of the cystic artery.

PMID- 22880509
TI  - Dyke-Davidoff-Masson syndrome.

PMID- 22880510
TI  - Lymphomatoid granulomatosis.

PMID- 22880511
TI  - Epileptic seizure due to neuroglial cyst.

PMID- 22880512
TI  - Central neurocytoma.

PMID- 22880513
TI  - Huge thymic cyst in an adult.

PMID- 22880514
TI  - Torsion of the wandering spleen.

PMID- 22880515
TI  - Round pneumonia.

PMID- 22880516
TI  - Diffuse intestinal ganglioneuromatosis of the ileum.

PMID- 22880517
TI  - Epipericardial fat necrosis.

PMID- 22880518
TI  - Fragile X-associated tremor/ataxia syndrome.

PMID- 22880519
TI  - Bilateral cervical spondylolysis.

PMID- 22880520
TI  - Emphysematous cystitis.

PMID- 22880521
TI  - Nodular regenerative hyperplasia of the liver and portal thrombosis.

PMID- 22880522
TI  - Synovial chondromatosis of the temporomandibular joint.

PMID- 22880523
TI  - Lung emphysema caused by marijuana smoking.

PMID- 22880524
TI  - Osteosarcoma of the maxilla.

PMID- 22880525
TI  - Medial plica syndrome of left knee.

PMID- 22880526
TI  - Clear cell sarcoma of the ankle.

PMID- 22880527
TI  - Duplicate inferior vena cava continuing as a hemiazygos continuation draining
      into the right atrium via persistent left superior vena cava.

PMID- 22880528
TI  - Idiopathic hypoparathyroidism as a cause of extensive intracranial calcification.

PMID- 22880529
TI  - Pulmonary Langerhans cell histiocytosis and eosinophilic granuloma.

PMID- 22880530
TI  - Intestinal intussusception in an infant.

PMID- 22880531
TI  - Subacute combined spinal degeneration caused by cobalamin deficiency.

PMID- 22880532
TI  - Spontaneous pneumomediastinum: a rare complication of idiopathic pulmonary
      fibrosis.

PMID- 22880533
TI  - Congenital bronchial atresia: a fortuitous diagnosis.

PMID- 22880534
TI  - Unusual cause of internal knee derangement.

PMID- 22880535
TI  - Proceedings of the Joint Meeting RBRS Bone Section and Nederlandse Vereniging
      Voor Skeletaradiologie, Leiden, The Netherlands, 25.0.3.2011-Part II. Tumors and
      tumorlike conditions of the calcaneous: the usual and the unusual.
AB  - The calcaneus is an uncommon site for involvement by tumors or tumorlike
      conditions of bone, although any lesion may involve the calcaneus. The purpose of
      this paper is to highlight the imaging features of common and uncommon tumors and
      tumorlike conditions occurring in the calcaneus. Typical case studies will
      illustrate the imaging findings on different imaging modalities.

PMID- 22880536
TI  - The medicalization of therapeutic communities in the era of health care reform.
AB  - Recent health care reform legislation has prompted greater efforts to divert
      substance abusers to addiction treatment facilities. A major component of reform
      has been the acknowledgement that mental health and addiction issues must be
      treated on a par with medical issues. The merger of the Haight Ashbury Free
      Clinics and Walden House offers a model for the medicalization of therapeutic
      communities to provide a medical home for previously underserved, marginalized
      populations.

PMID- 22880537
TI  - Specific ways brain SPECT imaging enhances clinical psychiatric practice.
AB  - Our objective was to ascertain in a prospective case series how often brain
      single photon emission computed tomography (SPECT) neuroimaging adds relevant
      information for diagnosis and/or treatment beyond current standard assessment
      tools in complex psychiatric cases. Charts of 109 consecutively evaluated
      outpatients from four psychiatrics clinics that routinely utilize SPECT imaging
      for complex cases were analyzed in two stages. In stage one, psychiatrists
      reviewed detailed clinical histories, mental status exams, and the structured
      clinical interview for DSM-IV, but not the results of SPECT studies, assigned a
      diagnosis based on DSM-IV criteria, and then developed a comprehensive treatment
      plan. In stage two, evaluators were given access to the SPECT studies for each
      patient. The addition of SPECT modified the diagnosis or treatment plan in 78.9%
      (n=86; rated level 2 or 3 change) of cases. The most clinically significant
      changes were undetected brain trauma (22.9%), toxicity patterns (22.9%) and the
      need for a structural imaging study (9.2%). Specific functional abnormalities
      were seen as follows that potentially could impact treatment: temporal lobe
      dysfunction (66.1%) and prefrontal hypoperfusion (47.7%). SPECT has the potential
      to add clinically meaningful information to enhance patient care beyond current
      assessment tools in complex or treatment resistant cases.

PMID- 22880538
TI  - The medicalization of addiction treatment professionals.
AB  - In a previous article, the authors described the changes initiated by recent
      health care legislation, and how those changes might affect the practice of
      medicine and the delivery of addiction services. This article reviews the same
      changes with respect to how they have the potential to change the practice
      activities of addiction physicians, addiction therapists, addiction counselors
      and addiction nurses, as well as the activities of administrators and service
      delivery financial personnel. Developments in delivery systems and the impact of
      those developments on professionals who work in addiction treatment are
      considered; current problems, potential solutions, and opportunities for
      clinicians under health reform are addressed. The goals envisioned for health
      system reform and the potential for realization of those goals via changes in
      addiction service delivery design and clinical practice are discussed.

PMID- 22880539
TI  - Chronic pain and addiction: challenging co-occurring disorders.
AB  - Chronic pain is commonly treated by prescribing an opioid medication. For those
      suffering from both chronic pain and substance dependence, barriers to adequate
      pain management increase. This often causes both disorders to exacerbate one
      another. Effective treatment may also be hampered by opioid-induced hyperalgesia,
      tolerance, physical dependence, "chemical coping," and diminished physical and
      emotional functioning. This article reviews current research trends, potential
      problems stemming from prescription opioid use, and suggestions for clinical
      practice.

PMID- 22880540
TI  - Cannabis as an adjunct to or substitute for opiates in the treatment of chronic
      pain.
AB  - There is a growing body of evidence to support the use of medical cannabis as an
      adjunct to or substitute for prescription opiates in the treatment of chronic
      pain. When used in conjunction with opiates, cannabinoids lead to a greater
      cumulative relief of pain, resulting in a reduction in the use of opiates (and
      associated side-effects) by patients in a clinical setting. Additionally,
      cannabinoids can prevent the development of tolerance to and withdrawal from
      opiates, and can even rekindle opiate analgesia after a prior dosage has become
      ineffective. Novel research suggests that cannabis may be useful in the treatment
      of problematic substance use. These findings suggest that increasing safe access
      to medical cannabis may reduce the personal and social harms associated with
      addiction, particularly in relation to the growing problematic use of
      pharmaceutical opiates. Despite a lack of regulatory oversight by federal
      governments in North America, community-based medical cannabis dispensaries have
      proven successful at supplying patients with a safe source of cannabis within an
      environment conducive to healing, and may be reducing the problematic use of
      pharmaceutical opiates and other potentially harmful substances in their
      communities.

PMID- 22880541
TI  - The addictive brain: all roads lead to dopamine.
AB  - This article will touch on theories, scientific research and conjecture about the
      evolutionary genetics of the brain function and the impact of genetic variants
      called polymorphisms on drug-seeking behavior. It will cover the neurological
      basis of pleasure-seeking and addiction, which affects multitudes in a global
      atmosphere where people are seeking "pleasure states".

PMID- 22880542
TI  - Substance users' perspectives on helpful and unhelpful confrontation:
      implications for recovery.
AB  - Substance users commonly face confrontations about their use from family,
      friends, peers, and professionals. Yet confrontation is controversial and not
      well understood. To better understand the effects of confrontation we conducted
      qualitative interviews with 38 substance users (82% male and 79% White) about
      their experiences of being confronted. Confrontation was defined as warnings
      about potential harm related to substance use. Results from coded transcripts
      indicated that helpful confrontations were those that were perceived as
      legitimate, offered hope and practical support, and were delivered by persons who
      were trusted and respected. Unhelpful confrontations were those that were
      perceived as hypocritical, overtly hostile, or occurring within embattled
      relationships. Experiences of directive, persistent confrontation varied.
      Limitations of the study include a small and relatively high functioning sample.
      We conclude that contextual factors are important in determining how
      confrontation is experienced. Larger studies with more diverse samples are
      warranted.

PMID- 22880544
TI  - Growing our own: building a native research team.
AB  - In 2006, American Indian/Alaska Natives (AI/AN) made up less than 1% of the
      science, engineering and health doctorates in the U.S. Early introduction of
      AI/AN students to research and continued opportunities are necessary to develop
      successful AI/AN researchers who can better serve their communities. This team
      was developed to form a cohort of American Indian students, staff and faculty
      interested in research and becoming researchers. Since implementation, the
      program grew from one student to over 20 AI students ranging from freshmen just
      entering college to doctoral students working to complete their dissertations.
      This article highlights the team growth, increasing structure, student needs and
      the faculty and staff involved. It further addresses the support and educational
      aspects of growing an ongoing, multidisciplinary research team committed to
      ethical research in Native communities. The team addresses substance use
      prevalence, the relationship of substance abuse to other mental health diagnoses,
      and treatment issues. The team includes weekly team meetings, a Blackboard site
      on the Internet that is populated with resources and focused on sharing materials
      and information, a weekly journal club discussion of research articles, and
      collaborative discussions on each project and the barriers and challenges that
      need to be addressed to move forward.

PMID- 22880543
TI  - Walking on: celebrating the journeys of Native American adolescents with
      substance use problems on the winding road to healing.
AB  - High rates of substance use and related problems have been long recognized as
      critical health issues for Native American adolescents. Unfortunately, no
      manualized interventions address the specific needs of Native American
      adolescents in a culturally appropriate manner. In 2006, the Cherokee Nation
      partnered with the University of Colorado to employ a community-based
      participatory research process to develop an intervention for Native American
      adolescents with substance use problems. The resulting intervention, Walking On,
      is an explicit blend of traditional Cherokee healing and spirituality with
      science-based practices such as cognitive behavioral therapy and contingency
      management and is designed to address the specific needs and worldviews of Native
      American adolescents with substance use problems and their families. Each
      individual and family session includes a brief assessment, a skill-building
      component, and a ceremony. A Weekly Circle (multifamily group) promotes sobriety
      and builds a community of healing. Early pilot study results suggest that Walking
      On is feasible for use in tribal substance abuse treatment programs. While
      Walking On shows early promise, the intervention will require further study to
      examine its efficacy.

PMID- 22880545
TI  - Lifetime substance use and HIV sexual risk behaviors predict treatment response
      to contingency management among homeless, substance-dependent MSM.
AB  - Homeless, substance-dependent men who have sex with men (MSM) continue to suffer
      health disparities, including high rates of HIV. One-hundred and thirty one
      homeless, substance-dependent MSM were randomized into a contingency management
      (CM) intervention to increase substance abstinence and health-promoting
      behaviors. Participants were recruited from a community-based, health
      education/risk reduction HIV prevention program and the research activities were
      also conducted at the community site. Secondary analyses were conducted to
      identify and characterize treatment responders (defined as participants in a
      contingency management intervention who scored at or above the median on three
      primary outcomes). Treatment responders were more likely to be Caucasian/White (p
      < .05), report fewer years of lifetime methamphetamine, cocaine, and
      polysubstance use (p < or = .05), and report more recent sexual partners and high
      risk sexual behaviors than nonresponders (p < .05). The application of evidence
      based interventions continues to be a public health priority, especially in the
      effort to implement effective interventions for use in community settings. The
      identification of both treatment responders and nonresponders is important for
      intervention development tailored to specific populations, both in service
      programs and research studies, to optimize outcomes among highly impacted
      populations.

PMID- 22880546
TI  - Familial risk factors favoring drug addiction onset.
AB  - This study, primarily aimed at identification of familial risk factors favoring
      drug addiction onset, was carried out throughout 2008 and 2009. The study
      comprised a total of 146 addicts and 134 control subjects. Based on the study
      outcome, it can be concluded that in the families the addicts were born into,
      familial risk factors capable of influencing their psychosocial development and
      favoring drug addiction onset had been statistically more frequently encountered
      during childhood and adolescence as compared to the controls. The results also
      indicated the need for further research into familial interrelations and the
      structure of the families addicts were born into, as well as the need for the
      implementation of family-based approaches to both drug addiction prevention and
      therapy.

PMID- 22880547
TI  - Craving dominates propofol addiction of an affected physician.
AB  - We report a case of severe dependence on propofol. For over a year, a 30-year-old
      male resident anesthesiologist injected 100-200 mg of propofol 20 to 40 times a
      day, reaching a daily total of up to 4 g. Compared to other withdrawal symptoms,
      craving for propofol was much more pronounced. Tolerance of the desired effects
      (cloudy and euphoric relaxation at his intravenous self-administration of 100 mg
      as well as sleep induction at 200 mg propofol) was not noticed by the patient. No
      other addiction was found in his history before he became dependent on propofol.
      This emphasizes that, especially with the patient's high injection rate, propofol
      has a powerful potential to be addictive. In most hospitals, the staff is put at
      risk by nonregulated dispensation and too easy access to this anesthetic drug.

PMID- 22880548
TI  - Zn2+ responsive bimodal magnetic resonance imaging and fluorescent imaging probe
      based on a gadolinium(III) complex.
AB  - A Zn(2+)-responsive bimodal magnetic resonance imaging (MRI) and luminescence
      imaging probe GdL was synthesized. The relaxivity and luminescence properties
      were examined. In the presence of 0.5 equiv of Zn(2+), the longitudinal
      relaxivity is increased from 3.8 mM(-1) s(-1) to 5.9 mM(-1) s(-1) at 23 MHz and
      25  degrees C with 55% enhancement, whereas the fluorescence exhibits a 7-fold
      increase. The Zn(2+) responsive imaging probe shows favorable selectivity and
      tolerance over a variety of biologically relevant anions and metal ions in
      physiological pH range for both relaxivity and luminescence. In vitro phantom
      images and confocal fluorescence images in living cells show that the bimodal
      Zn(2+) probe can effectively enhance T(1)-weighted imaging contrast and
      luminescence imaging effect through Zn(2+) coordination with excellent
      cellmembrane permeability and biocompatibility. Spectral and electrospray
      ionization mass spectrometry (ESI-MS) studies indicate that two different Zn(2+)
      bound species, (GdL)(2)Zn and GdLZn, are formed when 0.5 and 1 equiv of Zn(2+)
      are bound to GdL complex, respectively. Crystal structural determination and
      dysprosium-induced (17)O NMR shift (DIS) experiment demonstrate that the
      increased molecular weight and the improved molecular rigidity upon complexation
      of Zn(2+) with GdL is the primary factor for relaxivity enhancement. Significant
      enhancement of the luminescence is due to a heavy atom effect and much increased
      molecular rigidity upon Zn(2+) binding to 8-sulfonamidoquinoline chromophore.

PMID- 22880549
TI  - Appropriate degree of trust: deriving confidence metrics for automatic peak
      assignment in high-resolution mass spectrometry.
AB  - Techniques for deriving confidence metrics for the reliability of automatically
      assigned elemental formulas in complex spectra, from high-resolution mass
      spectrometers, are described. These metrics can help an analyst to place an
      appropriate degree of trust in the results obtained from automated spectral
      analysis of, for example, natural organic materials. To provide these metrics of
      confidence, common mass spectrometric tests for reliability of peak assignment
      (mass accuracy/error, relative ion abundance, and rings-plus-double-bonds
      equivalence) are combined with novel confidence metrics based on the
      interconnectivity and consistency of a mass difference or mass defect based peak
      inference network and on the confidence of the initial library matches. These are
      shown to provide improved peak assignment confidence over manual or simple
      automatic assignment methods.

PMID- 22880611
TI  - Mathematical aspects of physiologically structured populations: the contributions
      of J. A. J. Metz.

PMID- 22880609
TI  - Single-step nanoplasmonic VEGF165 aptasensor for early cancer diagnosis.
AB  - Early cancer diagnosis is very important for the prevention or mitigation of
      metastasis. However, effective and efficient methods are needed to improve the
      diagnosis and assessment of cancer. Here, we report a single-step detection
      method using a nanoplasmonic aptamer sensor (aptasensor), targeting a vascular
      endothelial growth factor-165 (VEGF(165)), a predominant biomarker of cancer
      angiogenesis. Our single-step detection is accomplished by (1) specific target
      recognition by an aptamer-target molecule interaction and (2) direct readouts of
      the target recognition. The readout is achieved by inactivation of surface
      plasmon enhancement of fluorescent probes preattached to the aptamers. Our
      aptasensor provides the appropriate sensitivity for clinical diagnostics with a
      wide range of linear detection from 25 pg/mL to 25 MUg/mL (=from 1.25 pM to 1.25
      MUM), high specificity for VEGF(165) against PDGF-BB, osteopontin (OPN),
      VEGF(121), NaCl, and temporal/thermal/biological stability. In experiments with
      100% serum and saliva from clinical samples, readouts of the aptasensor and an
      ELISA for VEGF(165) show good agreement within the limit of the ELISA kit. We
      envision that our developed aptasensor holds utilities for point-of-care cancer
      prognostics by incorporating simplicity in detection, low-cost for test, and
      required small sample volumes.

PMID- 22880612
TI  - An apparent paradox of horizontal and vertical disease transmission.
AB  - The question as to how the ratio of horizontal to vertical transmission depends
      on the coefficient of horizontal transmission is investigated in host-parasite
      models with one or two parasite strains. In an apparent paradox, this ratio
      decreases as the coefficient is increased provided that the ratio is taken at the
      equilibrium at which both host and parasite persist. Moreover, a completely
      vertically transmitted parasite strain that would go extinct on its own can
      coexist with a more harmful horizontally transmitted strain by protecting the
      host against it.

PMID- 22880613
TI  - Multi-patch deterministic and stochastic models for wildlife diseases.
AB  - Spatial heterogeneity and host demography have a direct impact on the persistence
      or extinction of a disease. Natural or human-made landscape features such as
      forests, rivers, roads, and crops are important to the persistence of wildlife
      diseases. Rabies, hantaviruses, and plague are just a few examples of wildlife
      diseases where spatial patterns of infection have been observed. We formulate
      multi-patch deterministic and stochastic epidemic models and use these models to
      investigate problems related to disease persistence and extinction. We show in
      some special cases that a unique disease-free equilibrium exists. In these cases,
      a basic reproduction number R(0) can be computed and shown to be bounded below
      and above by the minimum and maximum patch reproduction numbers R(j), j=1, ...,
      n. The basic reproduction number has a simple form when there is no movement or
      when all patches are identical or when the movement rate approaches infinity.
      Numerical examples of the deterministic and stochastic models illustrate the
      disease dynamics for different movement rates between three patches.

PMID- 22880614
TI  - Maintaining diversity in an artificially propagated population.
AB  - Populations may suffer unexpected loss or distortion of biodiversity as a
      consequence of strategies employed in artificial propagation programs. The
      Trinity River Fish Hatchery may have inadvertently experienced this while
      attempting to preserve diversity in a return time within a Chinook salmon
      population. We develop a model for this system and prove that the long-term
      distribution of return types converges and that it is strongly tied to the
      management strategy. Given estimates of heritabilities for return type and
      differential survival rates, an estimate of this long-term distribution can be
      computed easily.

PMID- 22880615
TI  - Modeling territory attendance and preening behavior in a seabird colony as
      functions of environmental conditions.
AB  - In previous studies we developed a general compartmental methodology for modeling
      animal behavior and applied the methodology to marine birds and mammals. In this
      study we used the methodology to construct a system of two differential equations
      to model the dynamics of territory attendance and preening in a gull colony on
      Protection Island, Strait of Juan de Fuca, Washington. We found that colony
      occupancy was driven primarily by abiotic environmental conditions, including
      tide height, time of day, solar elevation, and wind speed over open water. For
      birds in the colony, preening behavior was driven to some extent by abiotic
      environmental conditions (including time of day, solar elevation, humidity, and
      wind speed on the colony), but apparently was driven primarily by local and/or
      biotic effects not included in the model. In terms of R(2) values, the model
      explained 65% and 37% of the variability in colony occupancy and preening data,
      respectively, as a function of these six abiotic environmental factors.

PMID- 22880616
TI  - Infection-age structured epidemic models with behavior change or treatment.
AB  - We formulate infection-age structured susceptible-infective-removed (SIR) models
      with behavior change or treatment of infections. Individuals change their
      behavior or have treatment after they are infected. Using infection age as a
      continuous variable, and dividing infectives into discrete groups with different
      infection stages, respectively, we formulate a partial differential equation
      model and an ordinary differential equation model with behavior change or
      treatment. We derive explicit formulas for the reproductive number by linear
      stability analysis of the infection-free equilibrium, and explicit formulas for
      the unique endemic equilibrium, when it exists, for both models. These formulas
      provide mathematical theoretical frameworks for analysis of impact of behavior
      change or treatment of infection to the transmission dynamics of infectious
      diseases. We study several special cases and provide sensitivity analysis for the
      reproductive numbers with respect to model parameters based on those formulas.

PMID- 22880617
TI  - Analysis of a lottery competition model with limited nutrient availability.
AB  - How a plant species utilizes a limited nutrient is important for its survival.
      The purpose of this work is to examine how nutrient utilization mechanisms (for
      seed production) affect the coexistence of competing plant species. We construct
      a revised lottery model that uses one of three possible kinds of nutrient
      utilization functions. In all cases the models suggest that two species can
      coexist under certain circumstances, but that three species cannot coexist, at
      least when the nutrient utilization functions are continuous functions of
      nutrient uptake. However, in the discontinuous case three species can coexist in
      a state of sustained oscillations. The results suggest that one need pay close
      attention to the differences in the nutrient utilization mechanisms among
      competing plant species in order to ascertain the competitive outcome.

PMID- 22880618
TI  - The effect of weight loss surgery on the severity of psoriasis.

PMID- 22880620
TI  - Solvent- or temperature-controlled diastereoselective aldol reaction of methyl
      phenylacetate.
AB  - Unlike the enolboration-aldolization of methyl propanoate, the choice of either
      the solvent or temperature determines the diastereoselectivity during the
      enolboration-aldolization of methyl phenylacetate. In CH(2)Cl(2), the reaction
      favors the anti-pathway at -78  degrees C and the syn-pathway at rt. Conversely,
      the reaction produces the anti-isomer up to rt and the syn-isomer at refluxing
      temperatures in nonpolar solvents.

PMID- 22880619
TI  - Role of thrombomodulin gene in Indian population with coronary artery disease.
AB  - CONTEXT: Thrombomodulin (TM), a natural anticoagulant have been implicated in the
      pathogenesis of coronary artery disease (CAD) thus emphasizing its potential role
      as a biomarker. OBJECTIVES: To investigate the role of the TM genetic variants
      and soluble TM (sTM) plasma levels in Indian population with CAD. MATERIALS AND
      METHODS: This case-control study involved genotyping of the entire TM gene and
      sTM levels estimation in 266 subjects. RESULTS: None of the four TM genetic
      variants identified significantly increased CAD risk in the study population.
      However, further subgroup analysis revealed that in subjects <=49 years, C1418T
      variant (Ala455Val substitution) was significantly associated with CAD.
      CONCLUSION: The increased CAD risk in subjects <=49 years due to TM Ala455Val
      substitution is a promising finding. Further validation on large Indian cohorts
      is required in order to screen asymptomatic young subjects for CAD risk and to
      establish the clinical utility of Ala455Val substitution.

PMID- 22880621
TI  - Clinical safety of biosimilar recombinant human erythropoietins.
AB  - INTRODUCTION: A "biosimilar" or "similar biological medicinal product" is a
      biological agent that is similar in terms of quality, safety, and efficacy to an
      authorized reference biological medicine. Since the expiration of the epoetin
      alfa patent in Europe, three agents have received marketing authorization from
      the European Medicines Agency: Binocrit (epoetin alfa; aka Abseamed and Epoetin
      Alfa Hexal), Retacrit (epoetin zeta; aka Silapo), and Eporatio (epoetin theta;
      aka Biopoin and Ratioepo). AREAS COVERED: Using the EMA dossiers and journal
      publications, this article reviews clinical safety data for these products, with
      emphasis on serious/severe adverse events and a special consideration of
      immunogenicity, venous thromboembolism, and mortality. EXPERT OPINION: A review
      of the available safety evidence shows that all three agents discussed have
      similar safety profiles. None were statistically higher on safety parameters to
      what is known about ESA as a class, when stratified by population. As with ESAs
      in general, immunogenicity, venous thromboembolism, and mortality are all
      concerns. What is known about ESAs regarding safety can be extended to biosimilar
      erythropoietins. Since biosimilars are unique, complex biological molecules,
      safety profiles may evolve from common to differentiated, once long-term product
      specific safety data are available. Large-sample, long-term, observational
      studies of real-world practice will provide the heterogeneity and statistical
      power to demonstrate product-specific effectiveness and safety profiles.
      Statistically, out of the commercially available formulations of the three
      products reviewed, no single product is less or more safe.

PMID- 22880622
TI  - Cell survival fraction estimation based on the probability densities of domain
      and cell nucleus specific energies using improved microdosimetric kinetic models.
AB  - Estimation of the survival fractions of cells irradiated with various particles
      over a wide linear energy transfer (LET) range is of great importance in the
      treatment planning of charged-particle therapy. Two computational models were
      developed for estimating survival fractions based on the concept of the
      microdosimetric kinetic model. They were designated as the double-stochastic
      microdosimetric kinetic and stochastic microdosimetric kinetic models. The former
      model takes into account the stochastic natures of both domain and cell nucleus
      specific energies, whereas the latter model represents the stochastic nature of
      domain specific energy by its approximated mean value and variance to reduce the
      computational time. The probability densities of the domain and cell nucleus
      specific energies are the fundamental quantities for expressing survival
      fractions in these models. These densities are calculated using the
      microdosimetric and LET-estimator functions implemented in the Particle and Heavy
      Ion Transport code System (PHITS) in combination with the convolution or database
      method. Both the double-stochastic microdosimetric kinetic and stochastic
      microdosimetric kinetic models can reproduce the measured survival fractions for
      high-LET and high-dose irradiations, whereas a previously proposed
      microdosimetric kinetic model predicts lower values for these fractions, mainly
      due to intrinsic ignorance of the stochastic nature of cell nucleus specific
      energies in the calculation. The models we developed should contribute to a
      better understanding of the mechanism of cell inactivation, as well as improve
      the accuracy of treatment planning of charged-particle therapy.

PMID- 22880623
TI  - Age and hormonal status as determinants of cataractogenesis induced by ionizing
      radiation. II. Sparsely ionizing (low-LET) radiation.
AB  - Age at the time of exposure to sparsely ionizing radiation has been established
      as a key determinant of radiation cataractogenesis. However, while some reports
      suggest that the lenses of the young are hypersensitive, data from older studies
      are often conflicting and somewhat difficult to interpret when the radioresponse
      of young lenses is compared to that of adult lenses. Moreover, the mechanism of
      the age-response function for radiation cataractogenesis has yet to be
      identified. Since steroid sex hormones, notably estradiol, appear to play a role
      in age-related cataractogenesis, we hypothesized that the age response for
      radiation cataractogenesis could be dictated by estradiol status. We recently
      showed that exposure to high-linear energy transfer (LET) radiation resulted in a
      reduced latent period for, and enhanced progression of cataracts in rats that
      were 1 year old at the time of exposure compared to those that were 56 days old.
      However, the enhanced sensitivity of older lenses compared to younger lenses was
      independent of estradiol status. In the current study, we found that for 1-year
      old rats exposed to 10 Gy of low-LET (60)Co gamma rays, the rate of increase in
      the development of posterior and anterior subcapsular cataracts was higher in
      older ovary-intact rats compared to young rats. However, cataracts were detected
      much earlier in ovary-intact 56-day-old rats compared to 1-year-old rats,
      regardless of their treatment groups (ovary-intact, ovariectomized, or
      ovariectomized and implanted with capsules containing estradiol). Thus, despite a
      consistent estradiol response (potentiating effect of estrogen) within a given
      age group, the differences between the radiation response of old and young lenses
      cannot be accounted for solely by estradiol status.

PMID- 22880624
TI  - Executive function in rats is impaired by low (20 cGy) doses of 1 GeV/u (56)Fe
      particles.
AB  - Exposure to galactic cosmic radiation is a potential health risk in long-term
      space travel and represents a significant risk to the central nervous system. The
      most harmful component of galactic cosmic radiation is the HZE [high mass, highly
      charged (Z), high energy] particles, e.g., (56)Fe particle. In previous ground
      based experiments, exposure to doses of HZE-particle radiation that an astronaut
      will receive on a deep space mission (i.e., ~20 cGy) resulted in pronounced
      deficits in hippocampus-dependent learning and memory in rodents. Neurocognitive
      tasks that are dependent upon other regions of the brain, such as the striatum,
      are also impaired after exposure to low HZE-particle doses. These data raise the
      possibility that neurocognitive tasks regulated by the prefrontal cortex could
      also be impaired after exposure to mission relevant HZE-particle doses, which may
      prevent astronauts from performing complex executive functions. To assess the
      effects of mission relevant (20 cGy) doses of 1 GeV/u (56)Fe particles on
      executive function, male Wistar rats received either sham treatment or were
      irradiated and tested 3 months later for their ability to perform attentional set
      shifting. Compared to the controls, rats that received 20 cGy of 1 GeV/u (56)Fe
      particles showed significant impairments in their ability to complete the
      attentional set-shifting test, with only 17% of irradiated rats completing all
      stages as opposed to 78% of the control rats. The majority of failures (60%)
      occurred at the first reversal stage, and half of the remaining animals failed at
      the extra-dimensional shift phase of the studies. The irradiated rats that
      managed to complete the tasks did so with approximately the same ease as did the
      control rats. These observations suggest that exposure to mission relevant doses
      of 1 GeV/u (56)Fe particles results in the loss of functionality in several
      regions of the cortex: medical prefrontal cortex, anterior cingulated cortex,
      posterior cingulated cortex and the basal forebrain. Our observation that 20 cGy
      of 1 GeV/u (56)Fe particles is sufficient to impair the ability of rats to
      conduct attentional set-shifting raises the possibility that astronauts on
      prolonged deep space exploratory missions could subsequently develop deficits in
      executive function.

PMID- 22880625
TI  - Exploring temporospatial changes in glucose metabolic disorder, learning, and
      memory dysfunction in a rat model of diffuse axonal injury.
AB  - Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain
      injury and contributes significantly to cognitive deficits. The mechanisms
      underlying these cognitive deficits are often associated with complex metabolic
      alterations. However, the relationships between temporospatial alterations in
      cerebral glucose metabolism and the pathophysiology of DAI-related learning and
      memory dysfunction are not yet completely understood. We used a small animal
      positron emission tomography (PET) scanner with 2-[F-18]-fluoro-2-deoxy-D-glucose
      (18F-FDG) as a molecular probe to evaluate temporospatial glucose metabolism in
      vulnerable areas of rats with DAI. The Morris water maze (MWM) was used to
      evaluate the development and progression of learning and memory dysfunction.
      Compared to the sham-treated group, PET-MRI fusion images showed that glucose
      metabolism was reduced in animals with DAI. In addition, the standardized uptake
      value (SUV) of 18F-FDG was significantly decreased in the sensorimotor cortex,
      hippocampus, corpus callosum, caudate putamen, brain stem, and cerebellum at days
      1, 3, and 7 after injury. SUV returned to baseline levels by 30 days after
      injury. The escape latency of the injured group was significantly increased, and
      the percentages of distance travelled and time spent in the target quadrant were
      significantly decreased 1 month after injury. These effects persisted for 3
      months. SUVs in the hippocampus at the acute stage were significantly correlated
      with MWM performance during the recovery stage of DAI. These results demonstrate
      that microstructural injury-induced hypometabolism in the hippocampus at the
      acute stage are all significantly correlated with learning and memory
      dysfunctions during the recovery stage of DAI.

PMID- 22880627
TI  - Theoretical value of psychological testing.
AB  - Apart from their diagnostic value, psychological tests, especially the Rorschach
      test, have an important theoretical value for understanding psychopathology. They
      present a picture of a living person, in contrast to a picture of forces and
      agencies within the person. This rests on 2 advantages of tests over the usual
      psychiatric and psychoanalytic interviews: Tests are ahistorical and they present
      information primarily of a formal kind.

PMID- 22880626
TI  - Venous thromboembolism in nursing home residents: role of selected risk factors.
AB  - OBJECTIVES: To provide nursing home (NH)-specific estimates to assess whether
      venous thromboembolism (VTE) risk factors identified for the general population
      apply to NH residents. DESIGN: Population-based case-control study. SETTING:
      Olmsted County, Minnesota. PARTICIPANTS: All county residents with symptomatic
      objectively diagnosed incident VTE while resident in a NH from 1988 through 2000
      (N = 182) and two age-, sex-, calendar-year-matched non-VTE Olmsted County NH
      residents per case (N = 364). MEASUREMENTS: Provider-linked medical records were
      reviewed to obtain information on active malignancy and recent hospitalization,
      surgery, trauma, or fracture as of index date (case's VTE date; respective
      provider registration date for controls). Risk factor prevalence and VTE
      associated odds ratios (OR) were estimated and compared with previously obtained
      data for all Olmsted County residents from 1988 through 2000. For analyses, both
      groups were limited to individuals aged 65 and older. RESULTS: In NH residents,
      active malignancy, recent hospitalization, and recent surgery significantly
      increased VTE risk, but the magnitude of risk appeared much lower than general
      population estimates (e.g., for major surgery, OR = 2.5, 95% confidence interval
      (CI) = 1.4-4.3 for NH residents vs OR = 11, 95% CI = 7.0-17 for general
      population). In general, the prevalence of all evaluated VTE risk factors
      appeared much higher in NH controls than in general population controls.
      Thromboprophylaxis rates appeared higher for NH cases and controls than in the
      general population; disconcertingly, 47% of NH cases received prophylaxis.
      CONCLUSION: Although general population VTE risk factors (active cancer and
      recent hospitalization or surgery) can identify NH residents at higher risk for
      VTE, these exposures do not adequately stratify VTE risk for thromboprophylaxis
      recommendations. Further research into NH-specific risk factors and prophylaxis
      effectiveness is required.

PMID- 22880628
TI  - Design, synthesis, and antiviral activity evaluation of phenanthrene-based
      antofine derivatives.
AB  - On the basis of our previous structure-activity relationship (SAR) and antiviral
      mechanism studies, a series of phenanthrene-based antofine derivatives (1-12 and
      18-50) were designed targeting tobacco mosaic virus (TMV) RNA and synthesized and
      systematically evaluated for their antiviral activity against TMV. The bioassay
      results showed that most of these compounds exhibited good to excellent in vivo
      anti-TMV activity, of which compounds 19 and 27 displayed higher activity than
      commercial Ribavirin, thus emerging as potential inhibitors of plant virus. The
      novel concise structure provides another new template for antiviral studies.

PMID- 22880629
TI  - Brainstem auditory response findings in term neonates in intensive care unit.
AB  - OBJECTIVES: Whether term infants in neonatal intensive care unit (NICU) have
      brainstem auditory abnormalities remains to be determined. This study aimed to
      detect any abnormality in brainstem auditory function in term neonates who are
      admitted to NICU. METHODS: From a NICU, we recruited 55 term neonates with
      various perinatal problems. They were studied during the first week after birth
      using brainstem auditory evoked response (BAER), and the results were compared
      with normal term controls. RESULTS: Wave I and III latencies and I-III interpeak
      interval of the evoked response in the NICU term neonates were similar to those
      in the controls. Wave V latency and I-V and III-V interpeak intervals tended to
      be increased at 21/s clicks. The increase was more obvious at higher rates 51 and
      91/s. Analysis of variance revealed that at 21/s clicks only III-V interval was
      significantly increased (p < 0.05). At 51 and 91/s clicks, wave V latency and III
      V and I-V intervals were significantly increased (p < 0.05-0.01). The rates of
      the abnormalities were seen more at higher than at lower click rates. The
      amplitudes of waves I, III, and V in the NICU neonates were all slightly reduced,
      but none differed significantly from the controls. CONCLUSIONS: There are some
      abnormalities in BAER in term neonates in NICU, suggesting functional abnormality
      in the auditory brainstem in NICU infants.

PMID- 22880630
TI  - Reduced orbitofrontal and temporal grey matter in a community sample of
      maltreated children.
AB  - BACKGROUND: Childhood maltreatment is strongly associated with increased risk of
      psychiatric disorder. Previous neuroimaging studies have reported atypical neural
      structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and
      cerebellum in maltreated samples. It has been hypothesised that these structural
      differences may relate to increased psychiatric vulnerability. However, previous
      studies have typically recruited clinical samples with concurrent psychiatric
      disorders, or have poorly characterised the range of maltreatment experiences and
      levels of concurrent anxiety or depression, limiting the interpretation of the
      observed structural differences. METHODS: We used voxel-based morphometry to
      compare grey matter volume in a group of 18 children (mean age 12.01 years, SD =
      1.4), referred to community social services, with documented and well
      characterised experiences of maltreatment at home and a group of 20 nonmaltreated
      children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age,
      gender, cognitive ability, ethnicity and levels of anxiety, depression and
      posttraumatic stress symptoms. We examined five a priori regions of interest: the
      prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum. RESULTS:
      Maltreated children, compared to nonmaltreated peers, presented with reduced grey
      matter in the medial orbitofrontal cortex and the left middle temporal gyrus.
      CONCLUSIONS: The medial orbitofrontal cortex and the middle temporal gyrus have
      been implicated in reinforcement-based decision-making, emotion regulation and
      autobiographical memory, processes that are impaired in a number of psychiatric
      disorders associated with maltreatment. We speculate that grey matter disturbance
      in these regions in a community sample of maltreated children may represent a
      latent neurobiological risk factor for later psychopathology and heightened risk
      taking.

PMID- 22880631
TI  - Structure and bioactivity of steroidal saponins isolated from the roots of
      Chamaelirium luteum (false unicorn).
AB  - Phytochemical investigation of Chamaelirium luteum ("false unicorn") resulted in
      the isolation of 15 steroidal glycosides. Twelve of these (1, 2, 4-9, 11-13, and
      15) are apparently unique to this species, and eight of these (6-9, 11-13, and
      15) are previously unreported compounds; one (15) possesses a new steroidal
      aglycone. In addition, the absolute configuration of (23R,24S)-chiograsterol A
      (10) was defined, and its full spectroscopic characterization is reported for the
      first time. The structures and configurations of the saponins were determined
      using a combination of multistage mass spectrometry (MS(n)), 1D and 2D NMR
      experiments, and chemical degradation. The antiproliferative activity of nine
      compounds obtained in the present work, and eight related compounds generated in
      previous work, was compared in six human tumor cell lines, with aglycones 3 and
      10 and related derivatives 16, 17, 19, and 20 all displaying significant
      antiproliferative activity.

PMID- 22880632
TI  - Drosophila as a tool for studying the conserved genetics of pain.
AB  - Survival of all animals depends on an accurate representation of the world, and
      an organism must be capable of prioritizing and responding to potentially
      hazardous conditions. This ability is dependent on nociception, the sensory
      process allowing animals to detect and avoid potentially harmful stimuli.
      Nociception is the sensory process that results in the subjective experience of
      'pain' in humans. Because of its vital and broad role in animal biology,
      pain/nociception is a complex, whole-body physiological process that is under
      stringent evolutionary pressure. Here, we discuss the utility of Drosophila
      melanogaster as an emerging model organism for studying the conserved genetics of
      nociception, particularly with respect to recently developed high-throughput
      Drosophila 'pain' paradigms.

PMID- 22880634
TI  - Solid-to-solid oxidation of a vanadium(IV) to a vanadium(V) compound: chemisty of
      a sulfur-containing siderophore.
AB  - Visible light facilitates a solid-to-solid photochemical aerobic oxidation of a
      hunter-green microcrystalline oxidovanadium(IV) compound (1) to form a black
      powder of cis-dioxidovanadium(V) (2) at ambient temperature. The siderophore
      ligand pyridine-2,6-bis(thiocarboxylic acid), H(2)L, is secreted by a
      microorganism from the Pseudomonas genus. This irreversible transformation of a
      metal monooxo  to a metal dioxo complex in the solid state in the absence of
      solvent is unprecedented. It serves as a proof-of-concept reaction for green
      chemistry occurring in solid matrixes.

PMID- 22880633
TI  - One man's side effect is another man's therapeutic opportunity: targeting Kv7
      channels in smooth muscle disorders.
AB  - Retigabine is a first in class anticonvulsant that has recently undergone
      clinical trials to test its efficacy in epileptic patients. Retigabine's novel
      mechanism of action - activating Kv7 channels - suppresses neuronal activity to
      prevent seizure generation by hyperpolarizing the membrane potential and
      suppressing depolarizing surges. However, Kv7 channels are not expressed
      exclusively in neurones and data generated over the last decade have shown that
      Kv7 channels play a key role in various smooth muscle systems of the body. This
      review discusses the potential of targeting Kv7 channels in the smooth muscle to
      treat diseases such as hypertension, bladder instability, constipation and
      preterm labour.

PMID- 22880635
TI  - The behavior of ionic liquids under high pressure: a molecular dynamics
      simulation.
AB  - The effect of pressure on the structure, interionic interactions, and properties
      of the ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate
      ([C(4)mim][PF(6)]) was studied using an all-atom molecular dynamics simulation. A
      distinct conformational transition from anti (a) to gauche (g) form based on the
      deformation of the first C-C bond of the butyl chain was observed under high
      pressure, and the ratio of the a conformation that changed into the g
      conformation was 5.5% at 6000 bar. Under high pressure, the configuration of the
      a and g conformer for [C(4)mim](+) tends to make the alkyl chain distorted to the
      inside of the ring. Results on the density changes indicate a small increase from
      5000 to 6000 bar, which could be attributed to the writhing of the reducing end
      of the alkyl chain in the cation at higher pressure. These simulation results are
      well agreed with the experimental results. Transport properties were also
      calculated at different pressures. The results show that diffusion of the ions is
      reduced under high pressure, and the viscosity is dramatically enhanced.

PMID- 22880636
TI  - Clinical practice of new nurse graduates in Lebanon: challenges and perspectives
      through the eyes of preceptors.
AB  - New nurse graduates continue to experience difficulty balancing their preparation
      for practice with the expectations of the workplace. Few studies have explored
      the transition practices of nurse graduates through the challenges that they
      experience. This article presents the findings of a research study that explored
      the perceptions of preceptors regarding the clinical practice of nurse graduates
      using the qualitative multiple case study design. Twenty preceptors, selected
      from three recognized hospitals in Beirut, Lebanon, underwent semistructured
      interviews. Interview questions were based on an extensive literature review and
      on Tanner's (2006) judgment dimensions to categorize transition practices. An
      exhaustive discussion of the practices led to the identification of major themes
      that illustrate the clinical experiences of new nurse graduates: (1) inventory of
      competencies, (2) learning experience, (3) technical and theoretical mysteries,
      and (4) challenge of one's potential. The themes provide directives that
      curriculum leaders and executive nurses can use to plan initiatives that assist
      in the effective transition of new nurse graduates to the professional role.

PMID- 22880637
TI  - High-grade cervical neoplasia during pregnancy: diagnosis, management and
      postpartum findings.
AB  - OBJECTIVES: To study the prevalence of high-grade cervical intraepithelial
      neoplasia (CIN 2-3) during pregnancy and compare the rates of persistence,
      progression and regression of CIN 2-3 by colposcopically guided biopsy during
      pregnancy with respect to the postpartum period. Also to assess biopsy results
      during pregnancy and postpartum in relation to histopathology after treatment of
      lesions. POPULATION: Pregnant women with a histological diagnosis of CIN 2-3
      confirmed by colposcopically guided biopsy during pregnancy. METHODS: Between
      1989 and 2008, 11 700 pregnant women had cytologic and simultaneous colposcopic
      examinations during pregnancy. A colposcopically guided biopsy was performed when
      colposcopically suspicious high-grade lesions were detected, regardless of
      cytological results. Women with a histopathological diagnosis of CIN 2-3 during
      pregnancy were re-evaluated by colposcopically guided biopsy and treated during
      the postpartum period. RESULTS: CIN 2-3 was diagnosed in 56 of 11 700 (0.48%)
      pregnant women by biopsy. Thirty women complying with the protocol were assessed
      postpartum by histopathological studies, of whom 70% exhibited persistence, 13.3%
      progression and 16.7% regression of CIN 2-3. Twenty-nine were diagnosed by
      conization and one by colposcopically guided biopsy during the postpartum period,
      which revealed invasive cervical carcinoma. CONCLUSIONS: Due to the high rates of
      CIN 2-3 persistence during the postpartum period, we suggest that all patients in
      whom CIN 2-3 was diagnosed during pregnancy are biopsied and treated if necessary
      during the postpartum period, with at least a two-year follow-up control to
      prevent lesion recurrence.

PMID- 22880686
TI  - Nanochannels preparation and application in biosensing.
AB  - Selective transport in nanochannels (protein-based ion channels) is already used
      in living systems for electrical signaling in nerves and muscles, and this
      natural behavior is being approached for the application of biomimetic
      nanochannels in biosensors. On the basis of this principle, single nanochannels
      and nanochannel arrays seem to bring new advantages for biosensor development and
      applications. The purpose of this review is to provide a general comprehensive
      and critical overview on the latest trends in the development of nanochannel
      based biosensing systems. A detailed description and discussion of representative
      and recent works covering the main nanochannel fabrication techniques, nanoporous
      material characterizations, and especially their application in both
      electrochemical and optical sensing systems is given. The state-of-the-art of the
      developed technology may open the way to new advances in the integration of
      nanochannels with (bio)molecules and synthetic receptors for the development of
      novel biodetection systems that can be extended to many other applications with
      interest for clinical analysis, safety, and security as well as environmental and
      other industrial studies and applications.

PMID- 22880687
TI  - Design and synthesis of a ratiometric fluorescent chemosensor for Cu(II) with a
      fluorophore hybridization approach.
AB  - A new ratiometric fluorescent sensor for Cu(2+), WLN, has been developed via
      integrating a 1,8-naphthalimide fluorophore with 8-aminoquinoline. WLN exhibits a
      highly selective ratiometric response to Cu(2+) over other transition metal ions
      in aqueous media. Moreover, its practical ratiometric imaging ability for
      intracellular Cu(2+) has been confirmed in human breast adenocarcinoma cells (MCF
      7 cells) using a confocal microscope.

PMID- 22880688
TI  - When other separation techniques fail: compound-specific carbon isotope ratio
      analysis of sulfonamide containing pharmaceuticals by high-temperature-liquid
      chromatography-isotope ratio mass spectrometry.
AB  - Compound-specific isotope analysis (CISA) of nonvolatile analytes has been
      enabled by the introduction of the first commercial interface to hyphenate liquid
      chromatography with an isotope ratio mass spectrometer (LC-IRMS) in 2004, yet
      carbon isotope analysis of unpolar and moderately polar compounds is still a
      challenging task since only water as the eluent and no organic modifiers can be
      used to drive the separation in LC. The only way to increase the elution strength
      of aqueous eluents in reversed phase LC is the application of high temperatures
      to the mobile and stationary phases (HT-LC-IRMS). In this context we present the
      first method to determine carbon isotope ratios of pharmaceuticals that cannot be
      separated by already existing separation techniques for LC-IRMS, such as reversed
      phase chromatography at normal temperatures, ion-chromatography, and mixed mode
      chomatography. The pharmaceutical group of sulfonamides, which is generally mixed
      with trimethoprim in pharmaceutical products, has been chosen as probe compounds.
      Substance amounts as low as 0.3 MUg are sufficient to perform a precise analysis.
      The successful applicability and reproducibility of this method is shown by the
      analysis of real pharmaceutical samples. The method provides the first tool to
      study the pharmaceutical authenticity as well as degradation and mobility of such
      substances in the environment by using the stable isotopic signature of these
      compounds.

PMID- 22880689
TI  - Determination of the miss probabilities of individual S-state transitions during
      photosynthetic water oxidation by monitoring electron flow in photosystem II
      using FTIR spectroscopy.
AB  - Water oxidation by plants and cyanobacteria is performed via a light-driven cycle
      of five intermediates called S states (S(0)-S(4)) at the water oxidizing center
      (WOC) in photosystem II (PSII). The information about misses, i.e., the
      probabilities that the S-state transitions failed to advance, is crucial for
      detailed analysis of various spectroscopic data in investigations of the water
      oxidation mechanism. In this study, we have determined the miss probabilities of
      the individual S-state transitions using light-induced Fourier transform infrared
      (FTIR) difference spectroscopy. The extent of S-state transitions in the WOC upon
      each saturating flash was monitored by detecting the flow of electrons from the
      WOC to ferricyanide, an exogenous electron acceptor, using the CN stretching
      bands of ferricyanide and ferrocyanide. Simulation of the oscillation pattern of
      the flash-number dependence of the signal amplitude provided the miss
      probabilities for the S(0) -> S(1), S(1) -> S(2), S(2) -> S(3), and S(3) -> S(0)
      transitions (alpha(0)-alpha(3), respectively) without any assumption about
      fitting parameters. The results for PSII preparations from Thermosynechococcus
      elongatus and spinach showed a general tendency of misses in the order, alpha(0)
      <= alpha(1) < alpha(2) < alpha(3), indicating that a more oxidized WOC has a
      higher miss probability. A very similar result observed for the Y(D)-less mutant
      (D2-Y160F) of T. elongatus confirmed that Y(D) does not affect the estimated
      misses. It was further shown that NO(3)(-) treatment specifically increased
      alpha(3), consistent with inactivation of the S(3) state reported previously.
      These results demonstrate the usefulness of this FTIR method for estimating
      individual miss probabilities in the S-state cycle in elucidation of the
      molecular mechanism of photosynthetic water oxidation.

PMID- 22880690
TI  - Photo-induced charge separation across the graphene-TiO2 interface is faster than
      energy losses: a time-domain ab initio analysis.
AB  - Graphene-TiO(2) composites exhibit excellent potential for photovoltaic
      applications, provided that efficient photoinduced charge separation can be
      achieved at the interface. Once charges are separated, TiO(2) acts as an electron
      carrier, while graphene is an excellent hole conductor. However, charge
      separation competes with energy losses that can result in rapid electron-hole
      annihilation inside metallic graphene. Bearing this in mind, we investigate the
      mechanisms and, crucially, time scales of electron transfer and energy relaxation
      processes. Using nonadiabatic molecular dynamics formulated within the framework
      of time-domain density functional theory, we establish that the photoinduced
      electron transfer occurs several times faster than the electron-phonon energy
      relaxation (i.e., charge separation is efficient in the presence of electron
      phonon relaxation), thereby showing that graphene-TiO(2) interfaces can form the
      basis for photovoltaic and photocatalytic devices using visible light. We
      identify the mechanisms for charge separation and energy losses, both of which
      proceed by rapid, phonon-induced nonadiabatic transitions within the manifold of
      the electronic states. Electron injection is ultrafast, owing to strong
      electronic coupling between graphene and TiO(2). Injection is promoted by both
      out-of-plane graphene motions, which modulate the graphene-TiO(2) distance and
      interaction, and high-frequency bond stretching and bending vibrations, which
      generate large nonadiabatic coupling. Both electron injection and energy
      transfer, injection in particular, accelerate for photoexcited states that are
      delocalized between the two subsystems. The theoretical results show excellent
      agreement with the available experimental data [Adv. Funct. Mater. 2009, 19,
      3638]. The state-of-the-art simulation generates a detailed time-domain atomistic
      description of the interfacial charge separation and relaxation processes that
      are fundamental to a wide variety of applications, including catalysis,
      electrolysis, and photovoltaics.

PMID- 22880691
TI  - Ultra high-performance liquid chromatography with high-resolution mass
      spectrometry analysis of African mango (Irvingia gabonensis) seeds, extract, and
      related dietary supplements.
AB  - Dietary supplements based on an extract from Irvingia gabonensis (African mango,
      AM) seeds are one of the popular herbal weight loss dietary supplements in the
      U.S. market. The extract is believed to be a natural and healthy way to lose
      weight and improve overall health. However, the chemical composition of AM-based
      dietary supplements (AMDSs) has never been reported. In this study, the chemical
      constituents of AM seeds, AM seeds extract (AMSE), and different kinds of
      commercially available AMDSs have been investigated using an ultra high
      performance liquid chromatography with high resolution mass spectrometry method.
      Ellagic acid, mono-, di-, and tri-O-methyl-ellagic acids, and their glycosides
      were found as major components in AM seeds. These compounds may be used for
      quality control of AM extract and related dietary supplements.

PMID- 22880692
TI  - Community-based mental health counseling for children orphaned by AIDS in China.
AB  - There is an urgent need to develop scalable approaches to community-based mental
      health services for children in rural China and other developing countries
      involving task shifting from clinicians to trained community workers. Evidence is
      needed about the effectiveness of interventions for children affected by AIDS in
      rural areas. This article describes an intervention study aimed at developing,
      implementing, and evaluating a community-based counseling program for the AIDS
      orphans of Fuyang, Anhui Province, an area of central China where a tainted blood
      donation scheme infected countless farmers and left many children orphaned by
      AIDS. In China these children live in rural settings with no access to mental
      health services. The authors trained a group of community-based counselors to
      provide group counseling sessions focusing on self-awareness and communication
      and to provide a basic therapeutic approach for depression and anxiety. The
      authors conducted a baseline and two follow-up surveys of 39 children who met the
      clinical diagnostic criteria for anxiety and depression. There was a
      statistically significant improvement for the children on anxiety, but there was
      no statistically significant improvement on depression, with greatest gains
      immediately following the intervention. We demonstrated the feasibility of task
      shifting for mental health services in this setting.

PMID- 22880694
TI  - Dynamics of a plant-herbivore model.
AB  - We formulate a simple host-parasite type model to study the interaction of
      certain plants and herbivores. Our two-dimensional discrete-time model utilizes
      leaf and herbivore biomass as state variables. The parameter space consists of
      the growth rate of the host population and a parameter describing the damage
      inflicted by herbivores. We present insightful bifurcation diagrams in that
      parameter space. Bistability and a crisis of a strange attractor suggest two
      control strategies: reducing the population of the herbivore under some threshold
      or increasing the growth rate of the plant leaves.

PMID- 22880695
TI  - Immune response to a malaria infection: properties of a mathematical model.
AB  - We establish some properties of a within host mathematical model of malaria
      proposed by Recker et al. [M. Recker et al., Transient cross-reactive immune
      responses can orchestrate antigenic variation in malaria, Lett. Nature 429
      (2004), pp. 555-558; M. Recker and S. Gupta, Conflicting immune responses can
      prolong the length of infection in Plasmodium falciparum malaria, Bull. Math.
      Biol. 68 (2006), pp. 821-835.], which includes the role of the immune system
      during the infection. The model accounts for the antigenic variation exhibited by
      the malaria parasite (Plasmodium falciparum). We show that the model can exhibit
      a wide variety of dynamical behaviours. We provide criteria for global stability,
      competitive exclusion and persistence. We also demonstrate that the disease
      equilibrium can be destabilized by non-symmetric cross-reactive responses.

PMID- 22880696
TI  - Monotone bifurcation graphs.
AB  - In recent work by Angeli and the authors, it was shown that the stability and
      global behaviour of strongly monotone dynamical systems may be profitably studied
      using a technique that involves feedback decompositions into 'well-behaved'
      subsystems. The present paper generalizes the approach, so that it applies to a
      far larger class of systems. As an illustration, the techniques are used in the
      analysis of a nine-variable autoregulatory transcription network. Also,
      extensions to delay and reaction diffusion systems are considered.

PMID- 22880697
TI  - Dynamics of a delay differential equation model of hepatitis B virus infection.
AB  - We formulate and systematically study the global dynamics of a simple model of
      hepatitis B virus in terms of delay differential equations. This model has two
      important and novel features compared to the well-known basic virus model in the
      literature. Specifically, it makes use of the more realistic standard incidence
      function and explicitly incorporates a time delay in virus production. As a
      result, the infection reproduction number is no longer dependent on the patient
      liver size (number of initial healthy liver cells). For this model, the existence
      and the component values of the endemic steady state are explicitly dependent on
      the time delay. In certain biologically interesting limiting scenarios, a
      globally attractive endemic equilibrium can exist regardless of the time delay
      length.

PMID- 22880698
TI  - Global dynamics of a staged-progression model with amelioration for infectious
      diseases.
AB  - We analyze the global dynamics of a mathematical model for infectious diseases
      that progress through distinct stages within infected hosts with possibility of
      amelioration. An example of such diseases is HIV/AIDS that progresses through
      several stages with varying degrees of infectivity; amelioration can result from
      a host's immune action or more commonly from antiretroviral therapies, such as
      highly active antiretroviral therapy. For a general n-stage model with constant
      recruitment and bilinear incidence that incorporates amelioration, we prove that
      the global dynamics are completely determined by the basic reproduction number
      R(0). If R(0)<=1, then the disease-free equilibrium P(0) is globally
      asymptotically stable, and the disease always dies out. If R(0)>1, P(0) is
      unstable, a unique endemic equilibrium P* is globally asymptotically stable, and
      the disease persists at the endemic equilibrium. Impacts of amelioration on the
      basic reproduction number are also investigated.

PMID- 22880699
TI  - On existence and uniqueness of the carrying simplex for competitive dynamical
      systems.
AB  - Certain dynamical models of competition are shown to have a unique invariant
      hypersurface Sigma, having simple geometry and topology, such that every non-zero
      tractory is asymptotic to a trajectory in Sigma.

PMID- 22880700
TI  - Robust permanence and impermanence for stochastic replicator dynamics.
AB  - Garay and Hofbauer (SIAM J. Math. Anal. 34 (2003)) proposed sufficient conditions
      for robust permanence and impermanence of the deterministic replicator dynamics.
      We reconsider these conditions in the context of the stochastic replicator
      dynamics, which is obtained from its deterministic analogue by introducing
      Brownian perturbations of payoffs. When the deterministic replicator dynamics is
      permanent and the noise level small, the stochastic dynamics admits a unique
      ergodic distribution whose mass is concentrated near the maximal interior
      attractor of the unperturbed system; thus, permanence is robust against small
      unbounded stochastic perturbations. When the deterministic dynamics is
      impermanent and the noise level small or large, the stochastic dynamics converges
      to the boundary of the state space at an exponential rate.

PMID- 22880701
TI  - Bistable waves for a class of cooperative reaction-diffusion systems.
AB  - In this paper, we consider a class of coupled cooperative reaction-diffusion
      systems, in which one population (or subpopulation) diffuses while the other is
      sedentary. We use the shooting method to prove the existence of the bistable
      travelling wave, and then obtain its global attractivity with phase shift and
      uniqueness (up to translation) via the dynamical system approach. The results are
      applied to some specific examples of reaction-diffusion population models.

PMID- 22880702
TI  - Competition in a turbidostat for an inhibitory nutrient.
AB  - A model of competition in a turbidostat between two species for an inhibitory
      growth-limiting nutrient is considered. It is shown that the model has rich
      dynamics. A coexistence equilibrium and the washout equilibrium can be
      asymptotically stable simultaneously so that coexistence may depend on initial
      conditions. Under certain conditions, periodic coexistence of the two species
      occurs. There is a possibility that two species coexist, whereas one species dies
      out in the absence of its rival.

PMID- 22880703
TI  - An epidemic model with post-contact prophylaxis of distributed length I.
      Thresholds for disease persistence and extinction.
AB  - A possible control strategy against the spread of an infectious disease is the
      treatment with antimicrobials that are given prophylactically to those who had a
      contact with an infective person. The treatment continues until recovery or until
      it becomes obvious that there was no infection in the first place. The model
      considers susceptible, treated uninfected exposed, treated infected, (untreated)
      infectious, and recovered individuals. Since treatment lengths have an arbitrary
      distribution, the model system consists of ordinary differential and integral
      equations. A sharp threshold condition is established in terms of a basic
      replacement ratio (disease reproduction number) that separates disease extinction
      from uniform disease persistence. We use results from dynamical systems
      persistence theory proving the existence of a global compact attractor along the
      way. Existence and multiplicity of endemic equilibria are also studied.

PMID- 22880704
TI  - Effects of phase ratio and velocity conversion coefficient on the performance of
      the triple jump.
AB  - Phase ratio is a measure of effort distribution in the triple jump. Hop-dominant,
      balanced, and jump-dominant techniques were three triple jump techniques defined
      based on phase ratio. The purpose of this study was to determine the effect of
      the phase ratio on the performance of the triple jump. Three-dimensional
      kinematic data of 13 elite male triple jumpers were obtained during a
      competition. Computer simulations were performed using a biomechanical model of
      the triple jump to optimise the phase ratio for the longest actual distance using
      each of the three techniques for a given athlete with altered velocity conversion
      coefficients. The velocity conversion coefficient affected which technique
      achieved the longest actual distance. The actual distance obtained using the hop
      dominant technique was significantly longer than that obtained using the other
      two techniques (P = 0.007, P = 0.001) when the velocity coefficient was between
      0.35 and 0.55. The actual distance obtained using the jump-dominant technique was
      significantly longer than that obtained using the other two techniques (P =
      0.001, P = 0.002) when the velocity coefficient was between 0.80 and 1.30. No
      consistent optimum technique across participants and no significant difference in
      performance among the three techniques were found (P > 0.524) when the velocity
      coefficient was between 0.60 and 0.75.

PMID- 22880705
TI  - Serum 25-hydroxyvitamin D serum levels in a large German cohort of patients with
      melanoma.
AB  - BACKGROUND: Observational studies have suggested that 25-hydroxyvitamin D
      [25(OH)D] is associated with better outcomes in patients with malignant melanoma
      (MM). OBJECTIVES: To study the relationship between serum 25(OH)D levels and
      clinical parameters in a large German cohort of patients with MM. METHODS: We
      prospectively investigated the 25(OH)D serum levels of 764 patients with MM using
      the direct competitive chemiluminescence LIAISON immunoassay. Patients with MM
      who were taking 25(OH)D supplements were not included. RESULTS: Median serum
      25(OH)D baseline levels were 12.3 ng mL (lower quartile: 7.3 ng mL , upper
      quartile: 20.2 ng mL ). Of the 764 patients, 564 (73.8%) had 25(OH)D deficiency
      [25(OH)D < 20 ng mL ], 145 (18.8%) had 25(OH)D insufficiency [25(OH)D >= 20, < 30
      ng mL ] and only 55 (7.2%) had serum 25(OH)D levels within the normal range (>=
      30 ng mL ). Using a multiple regression model, lower 25(OH)D levels were
      significantly associated with higher Breslow tumour thickness (class: < 1 mm; 1-4
      mm; > 4 mm, regression coefficient -1.45, P = 0.028) and higher American Joint
      Committee on Cancer 2002 melanoma stage (regression coefficient: -0.79, P =
      0.036). CONCLUSIONS: In patients with MM, decreased 25(OH)D serum levels are
      associated with increased tumour thickness and advanced tumour stage. Hence,
      evidence is accumulating that patients with MM might benefit from 25(OH)D
      supplements.

PMID- 22880706
TI  - Uneven global distribution of randomized trials in hip fracture surgery.
AB  - BACKGROUND AND PURPOSE: Hip fractures are among the top causes of global
      disability. Conduction of high-quality studies such as randomized controlled
      trials to assess the effectiveness of interventions remains crucial. The
      geographic distribution of hip fracture studies is largely unknown. We wanted to
      make a global assessment of national contributions of randomized controlled
      trials on surgical interventions for hip fracture. METHODS: We performed a
      systematic search for randomized controlled trials on surgical interventions for
      hip fracture that were published from May 1970 to May 2011. Study information
      including sample size and study location was abstracted. The number of trials and
      cumulative sample size of hip fracture clinical trials were analyzed with respect
      to geographic region (city, country, and continent). RESULTS: We identified 199
      randomized trials investigating surgical interventions. Sweden ranked highest
      with 50 trials (8,941 patients). The United Kingdom followed with 40 trials
      (7,589 patients). Other countries contributed substantially less. The United
      States and Canada together contributed only a tenth of the total number of trials
      contributed by European countries. INTERPRETATION: Global contributions to
      randomized trials and the total number of patients recruited have been led by
      Scandinavian countries and the UK. Countries with few trials but a large burden
      of hip fractures have an opportunity to engage in high-quality research to
      resolve important surgical questions and improve the generalizability of study
      results.

PMID- 22880707
TI  - 5-year clinical and radiostereometric analysis (RSA) follow-up of 39 CUT femoral
      neck total hip prostheses in young osteoarthritis patients.
AB  - BACKGROUND: As the number of young patients receiving total hip arthroplasty
      increases, bone-saving implantations facilitating possible future revision, such
      as the CUT femoral neck prosthesis, are gaining importance. There have been few
      medium-term results reported for this prosthesis, however, and its migration
      pattern has not been analyzed. PATIENTS AND METHODS: 39 consecutive CUT femoral
      neck prostheses were implanted in 32 patients, mean age 37 (17-58) years, with
      symptomatic osteoarthritis and either less than 55 years of age or with an
      anatomic anomaly preventing implantation of a diaphyseal stem (n = 1). Patients
      were followed prospectively using routine clinical examination and
      radiostereometric analysis (RSA) at 6, 12, 26, and 52 weeks postoperatively and
      annually thereafter. This study evaluated the 5-year follow-up results. RESULTS:
      The mean Harris hip score increased from 26 (3-51) points preoperatively to 84
      (66-98), 86 (55-98), and 87 (47-98) points at 3, 12, and 60 months. 3 stems were
      revised: 1 after luxation following excessive subsidence due to an undersized
      component and 2 due to persistent strong thigh pain. 5-year survival was 95% (95%
      CI: 87-100). Initial migration varied widely in magnitude; median total tip
      migration was 0.42 mm (0.09-9.4) at 6 weeks, 0.92 mm (0.18-5.9) at 1 year, and
      1.10 mm (0.13-6.4) at 5 years. Even after high initial migration, stabilization
      was achieved in 31 of the 35 RSA-evaluable implants. 3 prostheses showed
      progressive continuous migration throughout the entire follow-up period, and were
      considered to be loose, suggesting reduced long-term survival. INTERPRETATION:
      Currently, we cannot recommend the CUT femoral neck prosthesis as a routine
      treatment option in (young) patients requiring THA. The CUT prosthesis may not
      reach the 90% survival benchmark at 10 years, and the prosthesis is difficult to
      implant. If initial stabilization is achieved, however, aseptic loosening is
      unlikely. A good clinical outcome was seen in the surviving prostheses. We will
      continue to follow this patient group.

PMID- 22880708
TI  - Good long-term outcome of synovectomy in advanced stages of the rheumatoid elbow.
AB  - BACKGROUND AND PURPOSE: Synovectomy is an effective procedure for management of
      the rheumatoid elbow at radiographically early stages (Larsen grades 1 and 2).
      However, its efficacy for advanced stages (Larsen grades 3-5) is controversial.
      We investigated the outcome of synovectomy for advanced stages of the rheumatoid
      elbow. METHODS: Between May 1985 and September 1994, synovectomy was performed
      for 67 rheumatoid elbows in 59 patients (mean age 52 (26-72) years, 54 women). 3
      elbows (3 patients) were lost to follow-up after mean 15 (10-23) years. Thus, 64
      elbows were evaluated clinically and radiographically. RESULTS: The mean Mayo
      elbow performance score (MEPS) improved from 42 (15-75) points preoperatively to
      78 (45-100) points at the final follow-up examination. In cases of Larsen grade
      5, the mean MEPS at final follow-up examination (69 points) was lower than those
      of Larsen grade 3 and 4 cases (80 and 79 points, respectively) (p < 0.01).
      Recurrence of synovitis was obvious in 20/67 elbows. 12 cases had a total elbow
      arthroplasty mean 13 years after the synovectomy. The 10-year, 15-year, and 20
      year survival rates were 97%, 75%, and 70%, respectively. INTERPRETATION: Our
      findings suggest that synovectomy for the rheumatoid elbow gives a good long-term
      outcome for radiographically judged destroyed joints of Larsen grades 3-4.

PMID- 22880709
TI  - Retrieval analysis of Harris-Galante I and II acetabular liners in situ for more
      than 10 years.
AB  - BACKGROUND AND PURPOSE: There have been few reports documenting the wear and
      oxidation performance of the polyethylene bearing surface of HGPI and HGPII THA
      devices. We evaluated retrieved HGPI and HGPII acetabular liners that had been in
      situ for more than 10 years and determined whether there was a relationship
      between clinical and radiographic factors, surface damage, wear, and oxidation.
      MATERIALS AND METHODS: 129 HGPI and II acetabular liners with implantation times
      of > 10 years were retrieved at 4 institutions between 1997 and 2010. The liners
      were made from a single resin and were gamma radiation-sterilized in air. Surface
      damage, linear wear, and oxidation index (OI) were assessed. Differences in
      clinical and radiographic factors, surface damage, linear wear, and OI for the 2
      designs were statistically evaluated separately and together. RESULTS: Articular
      surface damage and backside damage was similar in the 2 designs. The linear
      penetration rate was 0.14 (SD 0.07) mm/year for the HGPI liners and 0.12 (SD
      0.08) mm/year for the HGPII liners. For both cohorts, the rim had a higher OI
      than the articular surface. 74% of the liners had subsurface cracking and 24% had
      a complete fracture through the acetabular rim. INTERPRETATION: Despite
      modification of the HGP locking mechanism in the HGPII design, dissociation of
      the liner from the acetabular shell can still occur if fracture of the rim of the
      liner develops due to oxidative degradation.

PMID- 22880710
TI  - Denervation impairs bone regeneration during distraction osteogenesis in rabbit
      tibia lengthening.
AB  - BACKGROUND AND PURPOSES: The nervous system plays an important role in bone
      metabolism. However, the effect of denervation on bone formation during
      distraction osteogenesis (DO) remains unclear. We studied neural influence on
      bone regeneration during DO in a rabbit model. METHODS: 24 New Zealand male white
      rabbits underwent left tibial osteodistraction. Before distraction, the animals
      were randomly divided into group R (resected left sciatic nerve) and group I
      (intact left sciatic nerve). 8 weeks after completion of distraction, the animals
      were killed and the lengthened tibias were harvested for radiography, micro-CT,
      histological evaluation, and mechanical testing. RESULTS: New regenerated bone
      was present in the distraction gaps of all animals at the end of the study, as
      revealed by radiography, micro-CT, and histology. However, less new bone
      formation and a lower degree of mineralization were observed in group R. The
      mechanical strength of the distraction gap in group I was 1.3-fold greater than
      that in group R when measured using the 3-point bending test. INTERPRETATION: The
      results suggest that the nervous system plays an essential role during DO: the
      denervation appears to have an inhibitory effect on bone formation.

PMID- 22880711
TI  - High complication rate in the early experience of minimally invasive total hip
      arthroplasty by the direct anterior approach.
AB  - BACKGROUND AND PURPOSE: There is growing interest in minimally invasive surgery
      techniques in total hip arthroplasty (THA). In this study, we investigated the
      learning curve and the early complications of the direct anterior approach in hip
      replacement. METHODS: In the period January through December 2010, THA was
      performed in 46 patients for primary osteoarthritis, using the direct anterior
      approach. These cases were compared to a matched cohort of 46 patients who were
      operated on with a conventional posterolateral approach. All patients were
      followed for at least 1 year. RESULTS: Operating time was almost twice as long
      and mean blood loss was almost twice as much in the group with anterior approach.
      No learning effect was observed in this group regarding operating time or blood
      loss. Radiographic evaluation showed adequate placement of the implants in both
      groups. The early complication rate was higher in the anterior approach group.
      Mean time of hospital stay and functional outcome (with Harris hip score and
      Oxford hip score) were similar in both groups at the 1-year follow-up.
      INTERPRETATION: The direct anterior approach is a difficult technique, but
      adequate hip placement was achieved radiographically. Early results showed no
      improvement in functional outcome compared to the posterolateral approach, but
      there was a higher early complication rate. We did not observe any learning
      effect after 46 patients.

PMID- 22880712
TI  - Longitudinal migration and inducible displacement of the Mobility Total Ankle
      System.
AB  - BACKGROUND AND PURPOSE: RSA can be used for early detection of unstable implants.
      We assessed the micromotion of the Mobility Total Ankle System over 2 years, to
      evaluate the stability of the bone-implant interface using radiostereometric
      analysis measurements of longitudinal migration and inducible displacement.
      PATIENTS AND METHODS: 23 patients were implanted with the Mobility system. Median
      age was 62 (28-75) years and median BMI was 28.8 (26.0-34.5). Supine
      radiostereometric analysis examinations were done from postoperatively to the 2
      year follow-up. Standing examinations were taken from the 3-month to the 2-year
      follow-up. Migrations and displacements were assessed using model-based RSA
      software (v. 3.2). RESULTS: The median maximum total point motion (MTPM) for the
      implants at 2 years was 1.19 (0.39-1.95) mm for the talar component and 0.90
      (0.17-2.28) mm for the spherical tip of the tibial component. The general pattern
      for all patients was that the slope of the migration curves decreased over time.
      The main direction of motion for both components was that of subsidence. The
      median 2-year MTPM inducible displacement for the talar component was 0.49 (0.27
      1.15) mm, and it was 0.07 (0.03-0.68) mm for the tibial component tip.
      INTERPRETATION: The implants subside into the bone over time and under load. This
      corresponds to the direction of primary loading during standing or walking. This
      statistically significant motion may become a clinically significant finding that
      would correspond with premature implant failure.

PMID- 22880713
TI  - Infection of the fracture hematoma from skeletal traction in an asymptomatic HIV
      positive patient.

PMID- 22880714
TI  - Systemic intermittent parathyroid hormone treatment improves osseointegration of
      press-fit inserted implants in cancellous bone.
AB  - BACKGROUND AND PURPOSE: Intermittent administration of parathyroid hormone (PTH)
      has an anabolic effect on bone, as confirmed in human osteoporosis studies,
      distraction osteogenesis, and fracture healing. PTH in rat models leads to
      improved fixation of implants in low-density bone or screw insertion
      transcortically. MATERIAL AND METHODS: We examined the effect of human PTH (1-34)
      on the cancellous osseointegration of unloaded implants inserted press-fit in
      intact bone of higher animal species. 20 dogs were randomized to treatment with
      human PTH (1-34), 5 MUg/kg/day subcutaneously, or placebo for 4 weeks starting on
      the day after insertion of a cylindrical porous coated plasma-sprayed titanium
      alloy implant in the proximal metaphyseal cancellous bone of tibia.
      Osseointegration was evaluated by histomorphometry and fixation by push-out test
      to failure. RESULTS: Surface fraction of woven bone at the implant interface was
      statistically significantly higher in the PTH group by 1.4 fold with (median
      (interquartile range) 15% (13-18)) in the PTH group and 11% (7-13) in control.
      The fraction of lamellar bone was unaltered. No significant difference in bone or
      fibrous tissue was observed in the circumferential regions of 0-500, 500-1,000,
      and 1,000-2,000 MUm around the implant. Mechanically, the implants treated with
      PTH showed no significant differences in total energy absorption, maximum shear
      stiffness, or maximum shear strength. INTERPRETATION: Intermittent treatment with
      PTH (1-34) improved histological osseointegration of a prosthesis inserted press
      fit at surgery in cancellous bone, with no additional improvement of the initial
      mechanical fixation at this time point.

PMID- 22880715
TI  - Preliminary experience with the patient-specific templating total knee
      arthroplasty.
AB  - BACKGROUND AND PURPOSE: Patient-specific templating total knee arthroplasty (TKA)
      is a new method for alignment of a total knee arthroplasty that uses disposable
      guides. We present the results of the first 40 consecutive patients who were
      operated on using this technique. METHODS: In this case-control study, we
      compared blood loss, operation time, and alignment of 40 TKAs performed using a
      patient-specific templating alignment technique with values from a matched
      control group of patients who were operated on by conventional intramedullary
      alignment technique. Alignment of the mechanical axis of the leg and
      flexion/extension and varus/valgus of the individual prosthesis components were
      measured on standing, long-leg, and standard lateral digital radiographs. The
      fraction of outliers (> 3) was determined. RESULTS: Mean mechanical axis of
      templating TKAs was 181 degrees  with a fraction of outliers of 0.3, and mean
      mechanical axis of conventional TKAs was 179 (outlier fraction 0.5). Fraction of
      outliers in the frontal plane for femoral components was 0.05 in the templating
      TKAs and 0.4 in the conventional TKAs, and for tibial components the
      corresponding values were 0.2 and 0.2. In the templating TKAs and conventional
      TKAs, fraction of outliers in the sagittal plane was 0.4 and 0.9, respectively,
      for femoral components and 0.4 and 0.6 for tibial components. Mean operation time
      was 10 min shorter and blood loss was 60 mL less for templating TKA than for
      intramedullary-aligned TKAs. INTERPRETATION: Patient-specific templating TKA
      showed improved accuracy of alignment and a small reduction in blood loss and
      operating time compared to intramedullary-aligned TKA, but the fraction of
      outliers was relatively high. Larger RCTs are needed for further evaluation of
      the technique and to define the future role of patient-specific template
      alignment techniques for TKA.

PMID- 22880716
TI  - Soft tissue extension increases the risk of local recurrence after curettage with
      adjuvants for giant-cell tumor of the long bones.
AB  - BACKGROUND AND PURPOSE: Risk factors for local recurrence of giant-cell tumor of
      bone (GCTB) have mostly been studied in heterogeneous treatment groups, including
      resection and intralesional treatment. The aim of the study was the
      identification of individual risk factors after curettage with adjuvants in GCTB.
      METHODS: Of 147 patients treated for primary GCTB between 1981 and 2009, 93
      patients were included in this retrospective single-center study. All patients
      were treated with curettage and polymethylmethacrylate (PMMA) with (n = 75) or
      without (n = 18) phenol. Mean follow-up was 8 (2-24) years. Recurrence-free
      survival was assessed for treatment modalities. Age, sex, tumor location, soft
      tissue extension, and pathological fractures were scored for every patient and
      included in a Cox regression analysis. RESULTS: The recurrence rate after the
      first procedure was 25/93. Recurrence-free survival for PMMA and phenol and for
      PMMA alone was similar. Eventually, local control was achieved using 1 or
      multiple intralesional procedures in 85 patients. Resection was required in 8
      patients. A higher risk of local recurrence was found for soft tissue extension
      (HR = 5, 95% CI: 2-12), but not for age below 30, sex, location (distal radius
      vs. other), or pathological fracture. INTERPRETATION: Curettage with adjuvants is
      a feasible first-choice treatment option for GCTB, with good oncological outcome
      and joint preservation. Soft tissue extension strongly increased the risk of
      local recurrence, whereas age, sex, location, and pathological fractures did not.

PMID- 22880717
TI  - A study of elderly adults taking warfarin admitted with prolonged international
      normalized ratio: a community hospital's experience.
AB  - OBJECTIVES: To assess bleeding complications and outcome of individuals receiving
      oral anticoagulants who were admitted to the hospital with an international
      normalized ratio (INR) greater than 4 by comparing them according to age (<= 80,
      >80). DESIGN: Retrospective cohort study. SETTING: Community hospital.
      PARTICIPANTS: All individuals (N = 253) admitted to the Department of Internal
      Medicine over a period of 4 years with an INR greater than 4: Group I, aged 80
      and younger (n = 127); Group II, older than 80 (n = 126). Data included bleeding
      complications, survival, and quality of INR control before admission and up to 48
      months after admission. RESULTS: Atrial fibrillation was the most common
      indication for warfarin therapy. Its incidence was higher in the older group (88%
      vs 73%, P = .004). More elderly participants lived in nursing homes (23% vs 9.4%.
      P = .004) or received in-home assistance (38.9% vs 20.5%, P = .002). There was no
      difference in INR upon admission, duration of warfarin treatment, or frequency of
      INR tests before admission. The incidence of bleeding events was 18.1% in Group I
      and 12.7% in Group II (P = .30). Major bleeding events occurred in 1.6% of Group
      I and none of Group II (P = .50). During follow-up after the first admission, the
      incidence of INR greater than 4 was higher in Group II (87.3% vs 70%, P = .02),
      without a difference in the number of additional admissions or bleeding events.
      CONCLUSION: Primary care physicians can safely maintain warfarin treatment in
      elderly adults, even in those with a history of hospitalization for high INR,
      using frequent INR measurements.

PMID- 22880718
TI  - Computed tomography angiography: improving diagnostic yield and cost
      effectiveness in the initial evaluation of spontaneous nonsubarachnoid
      intracerebral hemorrhage.
AB  - OBJECT: Computed tomography angiography (CTA) is increasingly used as a screening
      tool in the investigation of spontaneous intracerebral hemorrhage (ICH). However,
      CTA carries additional costs and risks, necessitating its judicious use. The
      authors hypothesized that subsets of patients with nontraumatic, nonsubarachnoid
      ICH are unlikely to benefit from CTA as part of the diagnostic workup and that
      particular patient risk factors may be used to increase the yield of CTA in the
      detection of vascular sources. METHODS: The authors performed a retrospective
      analysis of 1376 patients admitted to Dartmouth-Hitchcock Medical Center with ICH
      over an 8-year period. Patients with subarachnoid hemorrhage, hemorrhagic
      conversion of ischemic infarcts, trauma, and known prior malignancy were excluded
      from the analysis, resulting in 257 patients for final analysis. Records were
      reviewed for medical risk factors, hemorrhage location, and correlation of CTA
      findings with final diagnosis. Multiple logistic regression analysis was used to
      investigate the combined effects of baseline variables of interest. Model
      selection was conducted using the stepwise method with p = 0.10 as the
      significance level for variable entry and p = 0.05 the significance level for
      variable retention. RESULTS: Computed tomography angiography studies detected
      vascular pathology in 34 patients (13.2%). Patient characteristics that were
      associated with a significantly higher likelihood of identifying a structural
      vascular lesion as the source of hemorrhage included patient age younger than 65
      years (OR = 16.36, p = 0.0039), female sex (OR = 14.9, p = 0.0126), nonsmokers
      (OR = 103.8, p = 0.0008), patients with intraventricular hemorrhage (OR = 9.42, p
      = 0.0379), and patients without hypertension (OR = 515.78, p < 0.0001). Patients
      who were older than 65 years of age, with a history of hypertension, and
      hemorrhage located in the cerebellum or basal ganglia were never found to have an
      identified structural source of hemorrhage on CTA. CONCLUSIONS: Patient
      characteristics and risk factors are important considerations when ordering
      diagnostic tests in the workup of nonsubarachnoid, nontraumatic spontaneous ICH.
      Although CTA is an accurate diagnostic examination, it can usually be omitted in
      the workup of patients with the described characteristics. The use of this
      algorithm has the potential to increase the yield, and thus the safety and cost
      effectiveness, of this diagnostic tool.

PMID- 22880719
TI  - Measuring surgical outcomes in neurosurgery: implementation, analysis, and
      auditing a prospective series of more than 5000 procedures.
AB  - OBJECT: Health care reform debate includes discussions regarding outcomes of
      surgical interventions. Yet quality of medical care, when judged as a health
      outcome, is difficult to define because of impediments affecting accuracy in data
      collection, analysis, and reporting. In this prospective study, the authors
      report the outcomes for neurosurgical treatment based on point-of-care
      interactions recorded in the electronic medical record (EMR). METHODS: The
      authors' neurosurgery practice collected outcome data for 19 physicians and
      ancillary personnel using the EMR. Data were analyzed for 5361 consecutive
      surgical cases, either elective or emergency procedures, performed during 2009 at
      multiple hospitals, offices, and an ambulatory spine surgery center. Main
      outcomes included complications, length of stay (LOS), and discharge disposition
      for all patients and for certain frequently performed procedures. Physicians,
      nurses, and other medical staff used validated scales to record the hospital LOS,
      complications, disposition at discharge, and return to work. RESULTS: Of the 5361
      surgical procedures performed, two-thirds were spinal procedures and one-third
      were cranial procedures. Organization-wide compliance with reporting rates of
      major complications improved throughout the year, from 80.7% in the first quarter
      to 90.3% in the fourth quarter. Auditing showed that rates of unreported
      complications decreased from 11% in the first quarter to 4% in the fourth
      quarter. Complication data were available for 4593 procedures (85.7%); of these,
      no complications were reported in 4367 (95.1%). Discharge dispositions reported
      were home in 86.2%, rehabilitation center in 8.9%, and nursing home in 2.5%.
      Major complications included culture-proven infection in 0.61%, CSF leak in
      0.89%, reoperation within the same hospitalization in 0.38%, and new neurological
      deficits in 0.77%. For the commonly performed procedures, the median hospital LOS
      was 3 days for craniotomy for aneurysm or intraaxial tumor and less than 1 day
      for angiogram, anterior cervical discectomy with fusion, or lumbar discectomy.
      CONCLUSIONS: With prospectively collected outcome data for more than 5000
      surgeries, the authors achieved their primary end point of institution-wide
      compliance and data accuracy. Components of this process included staged
      implementation with physician pilot studies and oversight, nurse participation,
      point-of-service data capture, EMR form modification, data auditing, and
      confidential surgeon reports.

PMID- 22880720
TI  - The therapeutic potential of ex vivo expanded CD133+ cells derived from human
      peripheral blood for peripheral nerve injuries.
AB  - OBJECT: CD133(+) cells have the potential to enhance histological and functional
      recovery from peripheral nerve injury. However, the number of CD133(+) cells
      safely obtained from human peripheral blood is extremely limited. To address this
      issue, the authors expanded CD133(+) cells derived from human peripheral blood
      using the serum-free expansion culture method and transplanted these ex vivo
      expanded cells into a model of sciatic nerve defect in rats. The purpose of this
      study was to determine the potential of ex vivo expanded CD133(+) cells to induce
      or enhance the repair of injured peripheral nerves. METHODS: Phosphate-buffered
      saline (PBS group [Group 1]), 10(5) fresh CD133(+) cells (fresh group [Group 2]),
      10(5) ex vivo expanded CD133(+) cells (expansion group [Group 3]), or 10(4) fresh
      CD133(+) cells (low-dose group [Group 4]) embedded in atelocollagen gel were
      transplanted into a silicone tube that was then used to bridge a 15-mm defect in
      the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery,
      histological and functional evaluations of the regenerated tissues were
      performed. RESULTS: After 1 week of expansion culture, the number of cells
      increased 9.6 +/- 3.3-fold. Based on the fluorescence-activated cell sorting
      analysis, it was demonstrated that the initial freshly isolated CD133(+) cell
      population contained 93.22% +/- 0.30% CD133(+) cells and further confirmed that
      the expanded cells had a purity of 59.02% +/- 1.58% CD133(+) cells. However, the
      histologically and functionally regenerated nerves bridging the defects were
      recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The
      nerves did not regenerate to bridge the defect in any of the rats in Group 1.
      CONCLUSIONS: The authors' results show that ex vivo expanded CD133(+) cells
      derived from human peripheral blood have a therapeutic potential similar to fresh
      CD133(+) cells for peripheral nerve injuries. The ex vivo procedure that can be
      used to expand CD133(+) cells without reducing their function represents a novel
      method for developing cell therapy for nerve defects in a clinical setting.

PMID- 22880722
TI  - Pressure buildup and brine migration during CO2 storage in multilayered aquifers.
AB  - Carbon dioxide injection into deep saline formations may induce large-scale
      pressure increases and migration of native fluid. Local high-conductivity
      features, such as improperly abandoned wells or conductive faults, could act as
      conduits for focused leakage of brine into shallow groundwater resources.
      Pressurized brine can also be pushed into overlying/underlying formations because
      of diffuse leakage through low-permeability aquitards, which occur over large
      areas and may allow for effective pressure bleed-off in the storage reservoirs.
      This study presents the application of a recently developed analytical solution
      for pressure buildup and leakage rates in a multilayered aquifer-aquitard system
      with focused and diffuse brine leakage. The accuracy of this single-phase
      analytical solution for estimating far-field flow processes is verified by
      comparison with a numerical simulation study that considers the details of two
      phase flow. We then present several example applications for a hypothetical CO2
      injection scenario (without consideration of two-phase flow) to demonstrate that
      the new solution is an efficient tool for analyzing regional pressure buildup in
      a multilayered system, as well as for gaining insights into the leakage processes
      of flow through aquitards, leaky wells, and/or leaky faults. This solution may be
      particularly useful when a large number of calculations needs to be performed,
      that is, for uncertainty quantification, for parameter estimation, or for the
      optimization of pressure-management schemes.

PMID- 22880723
TI  - Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic
      rats.
AB  - The antihyperglycemic effect of syringaldehyde (1), purified from the stems of
      Hibiscus taiwanensis, was investigated in streptozotocin-induced diabetic rats
      (STZ-diabetic rats) showing type-1 like diabetes mellitus. Bolus intravenous
      injection of 1 showed antihyperglycemic activity in a dose-dependent manner in
      STZ-diabetic rats. An effective dose of 7.2 mg/kg of 1 attenuated significantly
      the increase of plasma glucose induced by an intravenous glucose challenge test
      in normal rats. A glucose uptake test showed that 1 exhibits an increase of
      glucose uptake activity in a concentration-related manner. Moreover, an effect by
      1 was shown for insulin sensitivity in STZ-diabetic rats. The compound was found
      to increase insulin sensitivity in STZ-diabetic rats. These results suggest that
      syringaldehyde (1) can increase glucose utilization and insulin sensitivity to
      lower plasma glucose in diabetic rats.

PMID- 22880725
TI  - Spontaneous rupture of splenic artery aneurysm in pregnancy: is splenectomy
      always necessary?

PMID- 22880724
TI  - DNA methylation: a mechanism for embedding early life experiences in the genome.
AB  - Although epidemiological data provide evidence that early life experience plays a
      critical role in human development, the mechanism of how this works remains in
      question. Recent data from human and animal literature suggest that epigenetic
      changes, such as DNA methylation, are involved not only in cellular
      differentiation but also in the modulation of genome function in response to
      early life experience affecting gene function and the phenotype. Such modulations
      may serve as a mechanism for life-long genome adaptation. These changes seem to
      be widely distributed across the genome and to involve central and peripheral
      systems. Examining the environmental circumstances associated with the onset and
      reversal of DNA methylation will be critical for understanding risk and
      resiliency.

PMID- 22880726
TI  - A social-cognitive analysis of how young men become involved in male escorting.
AB  - This study employed a social-cognitive theoretical perspective to assess the
      interactions of behavioral, cognitive, and situational factors to understand
      better how young male sex workers (MSWs) entered the sex trade industry. As part
      of a larger project examining male escorts working for a single agency, MSWs (n =
      38) were interviewed about their work and personal lives. Interviews were
      transcribed and analyzed thematically. As predicted by a social-cognitive
      perspective, results supported reciprocal influences of behavior and environment,
      environment and cognition, and behavior and cognition. MSWs developed more self
      efficacy around sex work behaviors and more positive outcome expectations with
      experience; moral conflict and lack of attraction to clients limited MSWs' self
      efficacy. Key variables for sex work appeared to be cognitive in nature-mostly
      represented by a decreased commitment to normative social/sexual values, the
      specific nature of which may have varied by sexual orientation. Findings support
      the contention that social-cognitive theory can effectively model entry of young
      men into sex work. Social-cognitive theory provides a broad umbrella underneath
      which various explanations for male sex work can be gathered.

PMID- 22880727
TI  - Ova fecundity in Scottish Atlantic salmon Salmo salar: predictions, selective
      forces and causal mechanisms.
AB  - Ova fecundities of Scottish Atlantic salmon Salmo salar, predicted from log(10)
      regression of ova numbers and female fork length (L(F)), differed widely between
      upland and lowland stocks within the same river, whereas sea-age, river and year
      factors had insignificant effects on fecundity once L(F) was accounted for. For
      upland fish, the relationship between log(10)L(F) and log(10) ova mass (M(O)) was
      stable between two datasets collected 40 years apart. Although upland and lowland
      females both produced comparable log(10)M(O) (log(10)L(F))(-1), lowland females
      partitioned this into 45% more, but smaller ova, whereas upland females produced
      fewer, but larger, eggs. The possible causes and implications of this are
      discussed for evolutionary perspectives (lifetime production), population
      structure (local tributary v. large catchments; environmental effects),
      population dynamics and stability (density-dependent control mechanisms) and
      fisheries management (stock-recruitment; short and long-term stock
      sustainability).

PMID- 22880728
TI  - First cytogenetic studies of the genus Heptapterus (Actinopterygii,
      Siluriformes): karyotype differentiation and review of cytogenetic data on the
      Heptapteridae family.
AB  - The Neotropical fish Heptapterus mustelinus, collected in the Pindorama stream of
      the upper Parana River basin (Brazil), was studied cytogenetically, verifying 54
      chromosomes (26m + 18m + 4st + 6a). This diploid number has not been reported
      among the Heptapteridae that have been studied to date. Unlike most species of
      the family, there were multiple Ag-nucleolar organizer regions (NOR) and
      heterochromatin present in the centromeric region of most of the chromosomes of
      the complement, being Chromomycin A(3) (CMA(3)(+))/4',6-diamidino-2-phenylindole
      (DAPI(-)) in nine chromosomal pairs, besides the one that coincides with the Ag
      NORs. The data presented in this work reveal a different path in the karyotypic
      evolution of H. mustelinus when compared to the others Heptapteridae genera.

PMID- 22880729
TI  - The incomplete history of mitochondrial lineages between two rockfishes, Sebastes
      longispinis and Sebastes hubbsi (Scorpaeniformes: Scorpaenidae).
AB  - The genetic divergence between two closely related rockfishes, Sebastes
      longispinis and Sebastes hubbsi, was inferred from both mitochondrial DNA (mtDNA)
      sequence variations and amplified fragment length polymorphism (AFLP) markers.
      The two species were placed into two distinct clades in a neighbour-joining tree
      based on the AFLP data, clearly indicating that they represented separate
      species. Although this evidence, together with a previous morphological study,
      revealed clear differences between the two species, no obvious clustering of
      haplotypes by species was detected in the minimum spanning network inferred from
      sequence variations in the mtDNA control region (c. 500 base pairs). In fact, the
      significant Phi(ST)  estimates indicated only a restriction of gene flow between
      the two species. Uncorrected pairwise sequence differences in mtDNA between two
      species were small (1.8% at maximum, on the lower end of the range of control
      region divergence between previously studied sister species pairs), suggesting
      their speciation event as having been fairly recent. The incongruent results of
      AFLP and mtDNA phylogenies suggested incomplete lineage sorting and introgression
      of mtDNA in the course of the evolution of the two species. Differences in their
      main distributional ranges and the small level of sequence divergence in mtDNA
      suggests that speciation and dispersal may have been associated with glacio
      eustatic sea level fluctuations between the Japanese Archipelago and the Korean
      Peninsula during the past 0.4 million years.

PMID- 22880730
TI  - Boldness and aggressiveness in early and late hatched three-spined sticklebacks
      Gasterosteus aculeatus.
AB  - Levels of boldness and the degree of aggressiveness were compared in juvenile
      three-spined sticklebacks Gasterosteus aculeatus that had hatched early and late
      in the breeding season. The most striking result found in this study was that
      early hatched individuals were bolder when exploring a novel environment than
      were late-hatched individuals. No differences in levels of aggression between
      early and late hatchlings were found, but a relationship between boldness and
      aggressiveness was present regardless of hatching date. The implications of these
      findings are discussed in the light of research on individual variation in
      behaviour and the development of behavioural syndromes.

PMID- 22880731
TI  - The effect of temperature on embryonic and yolk-sac larval development in the
      burbot Lota lota.
AB  - The present study investigated the effect of various temperature regimes on
      embryonic and yolk-sac larval development of the burbot Lota lota. At constant
      temperature regimes a high percentage of ready-to-hatch embryos, hatched larvae
      and normally shaped larvae was observed at the lowest temperature (2 degrees  C),
      which significantly decreased with increasing temperatures (4 and 6 degrees  C).
      No larvae hatched at 9 degrees  C. The stream temperature regime had no effect on
      the percentage of ready-to-hatch embryos, but significantly decreased the
      percentage of hatched larvae and of normally shaped larvae. The lake temperature
      regime did not affect the viability variables. Also an abrupt temperature
      increase from 2 to 4 degrees  C after 8 days and from 2 to 9 degrees  C after 48
      days had no effect on the evaluated viability variables. For yolk-sac larvae no
      temperature related mortalities or abnormalities were observed between 2 and 9
      degrees  C.

PMID- 22880732
TI  - Inside the heads of David and Goliath: environmental effects on brain morphology
      among wild and growth-enhanced coho salmon Oncorhynchus kisutch.
AB  - Transgenic and wild-type individual coho salmon Oncorhynchus kisutch were reared
      in hatchery and near-natural stream conditions and their brain and structure
      sizes were determined. Animals reared in the hatchery grew larger and developed
      larger brains, both absolutely and when controlling for body size. In both
      environments, transgenics developed relatively smaller brains than wild types.
      Further, the volume of the optic tectum of both genotypes was larger in the
      hatchery animals and the cerebellum of transgenics was smaller when reared in
      near-natural streams. Finally, wild types developed a markedly smaller
      telencephalon under hatchery conditions. It is concluded that, apart from the
      environment, genetic factors that modulate somatic growth rate also have a strong
      influence on brain size and structure.

PMID- 22880733
TI  - Annotated list of demersal fishes occurring at Sedlo Seamount, Azores north-east
      central Atlantic Ocean.
AB  - Several fish surveys were carried out in recent years at Sedlo Seamount, Azores,
      north-eastern central Atlantic Ocean. An objective of the surveys was to
      determine the species composition of the demersal fish species living in the
      area. Four types of sampling gears (bottom trawl and three types of longline)
      were used at Sedlo Seamount resulting in very different species composition by
      gear and a very complete coverage of the fish fauna of the area. A list of fishes
      caught with these sampling methods is presented, along with other specific
      auxiliary information. Altogether 78 species from 43 families were listed for
      Sedlo Seamount, and as far as is known, 15 species were recorded for the first
      time for Azorean waters.

PMID- 22880734
TI  - Dietary preference and feeding selectivity of common dragonet Callionymus lyra in
      U.K.
AB  - The gut contents of 90 individuals of common dragonet Callionymus lyra were
      analysed, of which 76 contained prey, along with 100 corresponding benthic grab
      samples in order to assess the diet of C. lyra in relation to the availability of
      its prey in the environment. Forty-five prey taxa were identified in the diet
      from 350 potential prey taxa identified in the environment. Calculation of the
      index of relative importance (I(RI)) found the main food components were
      crustaceans (%I(RI) = 86.3), mostly the porcelain crab Pisidia longicornis
      (%I(RI) = 43) and other decapods (%I(RI) = 18). Polychaetes played only a
      supplementary role in the overall diet (%I(RI) = 12.5). This study demonstrated
      that C. lyra is predominantly an opportunistic feeder that can modify its feeding
      behaviour to exploit alternative, more abundant prey.

PMID- 22880735
TI  - 'Better off alone than in bad company': agonistic colour display in mimetic
      juveniles of two ephippid species.
AB  - Comparative field observations of agonistic interactions in juvenile leaf
      mimicking Platax orbicularis and Chaetodipterus faber (Ephippidae) were conducted
      in coastal waters of the Pacific and Atlantic Oceans. Similar agonistic behaviour
      was observed in the two species, in which individuals stopped displaying their
      mimetic colouration during encounters with conspecifics, to display conspicuous
      colours, such as transverse stripes along the body. These events were observed
      occasionally, almost invariably in individuals of smaller body size. Larger
      bodied individuals of both species spent less time in agonistic displays. The
      absolute size of the fish, however, did not appear to affect the outcome of the
      encounter, suggesting that dominance is a temporary condition, based on the
      relative size of the opponents during encounters.

PMID- 22880736
TI  - Metabolic and cardiorespiratory responses of summer flounder Paralichthys
      dentatus to hypoxia at two temperatures.
AB  - To quantify the tolerance of summer flounder Paralichthys dentatus to episodic
      hypoxia, resting metabolic rate, oxygen extraction, gill ventilation and heart
      rate were measured during acute progressive hypoxia at the fish's acclimation
      temperature (22 degrees  C) and after an acute temperature increase (to 30
      degrees  C). Mean +/-s.e. critical oxygen levels (i.e. the oxygen levels below
      which fish could not maintain aerobic metabolism) increased significantly from 27
      +/- 2% saturation (2.0 +/- 0.1 mg O(2) l(-1)) at 22 degrees  C to 39 +/- 2%
      saturation (2.4 +/- 0.1 mg O(2) l(-1)) at 30 degrees  C. Gill ventilation and
      oxygen extraction changed immediately with the onset of hypoxia at both
      temperatures. The fractional increase in gill ventilation (from normoxia to the
      lowest oxygen level tested) was much larger at 22 degrees  C (6.4-fold) than at
      30 degrees  C (2.7-fold). In contrast, the fractional decrease in oxygen
      extraction (from normoxia to the lowest oxygen levels tested) was similar at 22
      degrees  C (1.7-fold) and 30 degrees  C (1.5-fold), and clearly smaller than the
      fractional changes in gill ventilation. In contrast to the almost immediate
      effects of hypoxia on respiration, bradycardia was not observed until 20 and 30%
      oxygen saturation at 22 and 30 degrees  C, respectively. Bradycardia was,
      therefore, not observed until below critical oxygen levels. The critical oxygen
      levels at both temperatures were near or immediately below the accepted 2.3 mg
      O(2) l(-1) hypoxia threshold for survival, but the increase in the critical
      oxygen level at 30 degrees  C suggests a lower tolerance to hypoxia after an
      acute increase in temperature.

PMID- 22880737
TI  - Spatial distribution correspondence of a juvenile Atlantic salmon Salmo salar
      cohort from age 0+ to 1+ years.
AB  - The spatial distribution of Atlantic salmon Salmo salar young-of-the-year (0+)
      and 1 year old parr (1+) from the 2006 spawning cohort in a 5125 m reach of the
      River Skauga in central Norway was documented. A high degree of similarity was
      found between the distribution of 0+ and 1+ parr based on catches at 205
      transects sampled in both years. Cross-correlations and partial cross
      correlations (correcting for habitat variables) confirmed significant positive
      association between the two distributions on a small spatial scale (within 100 m)
      and a clear pattern of decreasing correlation with distance.

PMID- 22880738
TI  - Diet and feeding strategy of thornback ray Raja clavata.
AB  - The diet and feeding strategy of thornback ray Raja clavata, from the eastern
      central Adriatic Sea, were investigated. Stomach contents of 428 specimens, total
      length (L(T)) of 14.0-75.1 cm, were collected from commercial bottom trawls. The
      prey items identified in the stomachs belong to eight major groups: Cephalopoda,
      Polychaeta, Stomatopoda, Decapoda (Natantia and Reptantia), Mysidacea, Isopoda,
      Amphipoda and Teleostei. Decapods were the most important prey (index of relative
      important, %I(RI) ,= 72.8) followed by teleosts (%I(RI) = 20.4), whereas other
      prey groups were only occasionally ingested. Small-sized individuals (<25 cm
      L(T)) fed primarily on small crustaceans (mysids and amphipods), whereas large
      sized specimens consumed larger prey, such as decapods, cephalopods and teleosts.
      Diet composition showed little seasonal variation; decapods were the most
      important prey in all seasons. There was high dietary similarity between sampling
      locations. The percentage of empty stomachs did not differ significantly among
      size classes and seasons. In terms of composition by species, the diet of R.
      clavata was characterized by a variety of rare or unimportant prey. As a result,
      R. clavata could be considered a generalist predator.

PMID- 22880739
TI  - Aspects of the biology of Galaxias maculatus.
AB  - The biology of three landlocked and a riverine population of Galaxias maculatus
      were examined in western Victoria, Australia. All systems supported reproducing
      populations of these fish, including Lake Corangamite which had salinities that
      on occasion reached 82. Spawning sites in Lake Corangamite were located in
      adjacent tributaries and not in the main lake as was the case for other
      populations. The smallest fish were found in the fresh water Lake Purrumbete and
      the largest in the hypersaline Lake Corangamite. The size at which 50% of the
      population attained sexual maturity varied across sites, with fish maturing at a
      smaller size in Lake Purrumbete, followed by the Merri River, Lake Bullen Merri
      and Lake Corangamite. Condition was higher in the freshwater Lake Purrumbete and
      there was no relationship between condition and temperature, conductivity,
      turbidity and pH; but there was a positive relationship between condition and
      dissolved oxygen. Length frequency analysis suggested that the majority of fishes
      live for a year.

PMID- 22880741
TI  - Behavioural fever boosts the inflammatory response in rainbow trout Oncorhynchus
      mykiss.
AB  - Behavioural fever, manifested as an increased preferred temperature, was shown in
      rainbow trout Oncorhynchus mykiss following an injection of bacterial
      lipopolysaccharide. Simulated behavioural fever, through a 2.5 degrees  C water
      temperature rise following bacterial lipopolysaccharide injection, enhanced the
      expression of the cytokine interleukin-1beta, in comparison with an untreated
      group held at the initial temperature. The present findings show that an
      important mediator in the immune response can be boosted through behavioural
      fever in fishes.

PMID- 22880740
TI  - Embryonic development in ballan wrasse Labrus bergylta.
AB  - Eight primary embryonic developmental stages were assigned to eggs of ballan
      wrasse Labrus bergylta using key morphological features following standardized
      nomenclature: Ia, Ib, II, III, IV, V, VI and VI+, reared from single family
      clutches under comparable environmental conditions in Ireland and Norway.
      Development in L. bergylta is typical of demersal marine finfish species with a
      short egg stage. Hatching occurred c. 123 h post-fertilization (hpf) equivalent
      to 62.5 degree days at 12.2 +/- 1.10 degrees  C (mean +/-S.D.), after which the
      larvae swam intermittently near the surface of the water column.

PMID- 22880742
TI  - The chemical cues of male sea lice Lepeophtheirus salmonis encourage others to
      move between host Atlantic salmon Salmo salar.
AB  - Adult male sea lice Lepeophtheirus salmonis were more likely to leave host fish
      Atlantic salmon Salmo salar if they detected the chemical cues of other adult
      male lice than if they detect cues of female lice. The detection of both male and
      female chemical cues yielded an intermediate response. These results suggest that
      males use chemical cues to balance competition for resources and mate
      acquisition, and they highlight the need for further studies of the chemical
      ecology of this important parasite.

PMID- 22880743
TI  - The in vitro blood-O(2)  affinity of triploid rainbow trout Oncorhynchus mykiss
      at different temperatures and CO(2)  tensions.
AB  - Blood-O(2)  affinity, Hill number and predicted arterial-O(2)  saturation did not
      differ between diploid (2N) and triploid (3N) rainbow trout Oncorhynchus mykiss
      blood when compared under various temperature and CO(2)  partial pressure
      combinations. These results suggest that reduced hypoxia and warm-water tolerance
      and aerobic capacity of 3N fishes are not due to altered blood-O(2)  affinity.
      Further investigation into O(2)  transport-diffusion capacity and intracellular
      pH within 3N fishes may further unravel the mechanisms behind reduced 3N
      tolerance of suboptimal environments.

PMID- 22880744
TI  - First record of the deep-water whalefish Cetichthys indagator (Actinopterygii:
      Cetomimidae) in the North Atlantic Ocean.
AB  - The whalefish Cetichthys indagator is reported for the first time in the North
      Atlantic Ocean. This record increases to five the number of specimens ever caught
      and represents the northernmost occurrence of this species in the northern
      hemisphere.

PMID- 22880745
TI  - Aspects of the biology of the pygmy ribbontail catshark Eridacnis radcliffei
      (Proscylliidae: Carcharhiniformes) from the south-west coast of India.
AB  - Biological data are presented for the pygmy ribbontail catshark Eridacnis
      radcliffei based on specimens collected from the by-catch of the commercial deep
      sea shrimp trawl fishery operating in the Arabian Sea off the south-west coast of
      India. A total of 549 individuals, from 101 to 257 mm total length (L(T)) and 2.2
      to 56 g, were collected. The L(T) at first maturity (L(T50)) of females and males
      was estimated at 183 and 170 mm, respectively, and analysis of stomach contents
      revealed that E. radcliffei feeds primarily on crustaceans.

PMID- 22880747
TI  - Painful gains: missense mutations in SCN9A and idiopathic small nerve fibre
      neuropathy.

PMID- 22880748
TI  - Stochastic hybrid delay population dynamics: well-posed models and extinction.
AB  - Nonlinear differential equations have been used for decades for studying
      fluctuations in the populations of species, interactions of species with the
      environment, and competition and symbiosis between species. Over the years, the
      original non-linear models have been embellished with delay terms, stochastic
      terms and more recently discrete dynamics. In this paper, we investigate
      stochastic hybrid delay population dynamics (SHDPD), a very general class of
      population dynamics that comprises all of these phenomena. For this class of
      systems, we provide sufficient conditions to ensure that SHDPD have global
      positive, ultimately bounded solutions, a minimum requirement for a realistic,
      well-posed model. We then study the question of extinction and establish
      conditions under which an ecosystem modelled by SHDPD is doomed.

PMID- 22880749
TI  - Ecology and evolution of symbiosis in metapopulations.
AB  - We present a model for symbionts in plant host metapopulation. Symbionts are
      assumed not only to form a systemic infection throughout the host and pass into
      the host seeds, but also to reproduce and infect new plants by spores. Thus, we
      study a metapopulation of qualitatively identical patches coupled through seeds
      and spores dispersal. Symbionts that are only vertically inherited cannot persist
      in such a uniform environment if they lower the host's fitness. They have to be
      beneficial in order to coexist with the host if they are not perfectly
      transmitted to the seeds; but evolution selects for 100% fidelity of infection
      inheritance. In this model we want to see how mixed strategies (both vertical and
      horizontal infection) affect the coexistence of uninfected and infected plants at
      equilibrium; also, what would evolution do for the host, for the symbionts and
      for their association. We present a detailed classification of the possible
      equilibria with examples. The stability of the steady states is rigorously proved
      for the first time in a metapopulation set-up.

PMID- 22880750
TI  - Asymptotic behaviour of the non-autonomous competing two-species Lotka-Volterra
      models with impulsive effect.
AB  - In this paper, the nonautonomous competing two-species Lotka-Volterra models with
      impulsive effect are considered, where all the parameters are time-dependent and
      asymptotically approach the corresponding periodic functions. Under some
      conditions, it is shown that the semi-trivial positive solutions of the models
      asymptotically approach the semi-trivial positive periodic solutions of the
      corresponding periodic system. It is also shown that the positive solution of the
      models asymptotically approach the positive periodic solution of the
      corresponding periodic system.

PMID- 22880751
TI  - Derivation of stochastic partial differential equations for size- and age
      structured populations.
AB  - Stochastic partial differential equations (SPDEs) for size-structured and age-
      and size-structured populations are derived from basic principles, i.e. from the
      changes that occur in a small time interval. Discrete stochastic models of size
      structured and age-structured populations are constructed, carefully taking into
      account the inherent randomness in births, deaths, and size changes. As the time
      interval decreases, the discrete stochastic models lead to systems of Ito
      stochastic differential equations. As the size and age intervals decrease, SPDEs
      are derived for size-structured and age- and size-structured populations.
      Comparisons between numerical solutions of the SPDEs and independently formulated
      Monte Carlo calculations support the accuracy of the derivations.

PMID- 22880752
TI  - Continuous-time predator-prey models with parasites.
AB  - We study a deterministic continuous-time predator-prey model with parasites,
      where the prey population is the intermediate host for the parasites. It is
      assumed that the parasites can affect the behavior of the predator-prey
      interaction due to infection. The asymptotic dynamics of the system are
      investigated. A stochastic version of the model is also presented and numerically
      simulated. We then compare and contrast the two types of models.

PMID- 22880753
TI  - Synthesis and structural characterization of heterometallic thorium aluminum
      polynuclear molecular clusters.
AB  - Aluminum can undergo hydrolysis in aqueous solutions leading to the formation of
      soluble molecular clusters, including polynuclear species that range from 1 to 2
      nm in diameter. While the behavior of aluminum has been extensively investigated,
      much less is known about the hydrolysis of more complex mixed-metal systems. This
      study focuses on the structural characteristics of heterometallic thorium
      aluminum molecular species that may have important implications for the
      speciation of tetravalent actinides in radioactive waste streams and
      environmental systems. Two mixed metal (Th(4+)/Al(3+)) polynuclear species have
      been synthesized under ambient conditions and structurally characterized by
      single-crystal X-ray diffraction.
      [Th(2)Al(6)(OH)(14)(H(2)O)(12)(hedta)(2)](NO(3))(6)(H(2)O)(12) (ThAl1)
      crystallizes in space group P2(1)/c with unit cell parameters of a = 11.198(1) A,
      b = 14.210(2) A, c = 23.115(3) A, and beta = 96.375 degrees  and
      [Th(2)Al(8)(OH)(12)(H(2)O)(10)(hdpta)(4)](H(2)O)(21) (ThAl2) was modeled in P1
      with a = 13.136(4) A, b = 14.481(4) A, c = 15.819(4) A, alpha = 78.480(9) degrees
      , beta = 65.666(8) degrees , gamma = 78.272(8) degrees . Infrared spectra were
      collected on both compounds, confirming complexation of the ligand to the metal
      center, and thermogravimetric analysis indicated that the thermal degradation of
      these compounds resulted in the formation of an amorphous product at high
      temperatures. These mixed metal species have topological relationships to
      previously characterized aluminum-based polynuclear species and may provide
      insights into the adsorption of tetravalent actinides on colloidal or mineral
      surfaces.

PMID- 22880755
TI  - Caregiver's HIV disclosure to children 12 years and under: a review and analysis
      of the evidence.
AB  - A systematic review and analysis of the empirical evidence through June 2010 on
      HIV disclosure to children 12 and under was conducted using methods validated by
      the Cochrane group. Fifteen articles focusing on caregiver disclosure (255 total)
      were analyzed using GradePro 3 software. Results suggest that there is evidence
      of health and future care planning benefit for HIV+ and healthy children (12 and
      under) of HIV+ caregivers if the caregiver discloses his/her HIV status to them.
      Children of the maturity of school age youth (e.g., beginning at 6 years and
      continuing through 12) can be told of their caregivers' HIV status, while younger
      children may be informed partially in an age-appropriate manner.

PMID- 22880754
TI  - Nuclear magnetic resonance structure and dynamics of the response regulator
      Sma0114 from Sinorhizobium meliloti.
AB  - Receiver domains control intracellular responses triggered by signal transduction
      in bacterial two-component systems. Here, we report the solution nuclear magnetic
      resonance structure and dynamics of Sma0114 from the bacterium Sinorhizobium
      meliloti, the first such characterization of a receiver domain from the HWE
      kinase family of two-component systems. The structure of Sma0114 adopts a
      prototypical alpha(5)/beta(5) Rossman fold but has features that set it apart
      from other receiver domains. The fourth beta-strand of Sma0114 houses a PFxFATGY
      sequence motif, common to many HWE-kinase-associated receiver domains. This
      sequence motif in Sma0114 may substitute for the conserved Y-T coupling
      mechanism, which propagates conformational transitions in the 455 (alpha4-beta5
      alpha5) faces of receiver domains, to prime them for binding downstream effectors
      once they become activated by phosphorylation. In addition, the fourth alpha
      helix of the consensus 455 face in Sma0114 is replaced with a segment that shows
      high flexibility on the pico- to nanosecond time scale by (15)N relaxation data.
      Secondary structure prediction analysis suggests that the absence of helix alpha4
      may be a conserved property of the HWE-kinase-associated family of receiver
      domains to which Sma0114 belongs. In spite of these differences, Sma0114 has a
      conserved active site, binds divalent metal ions such as Mg(2+) and Ca(2+) that
      are required for phosphorylation, and exhibits micro- to millisecond active-site
      dynamics similar to those of other receiver domains. Taken together, our results
      suggest that Sma0114 has a conserved active site but differs from typical
      receiver domains in the structure of the 455 face that is used to effect signal
      transduction following activation.

PMID- 22880797
TI  - DNA methylation analysis triggered by bulge specific immuno-recognition.
AB  - We report the sequence-selective discrimination of the cytosine methylation
      status in DNA with anti methylcytosine antibody for the first time. This was
      realized by employing an affinity measurement involving the target methylcytosine
      in a bulge region and anti methylcytosine antibody, following hybridization with
      a bulge-inducing DNA to ensure that only the target methylcytosine is located in
      the bulge. The affinity of the antibody for methylcytosine in the bulge was 79%
      of that in a single strand of DNA; however, the affinity for nontarget
      methylcytosine in a double strand of DNA decreased greatly. This is because the
      antibody cannot bind with an inwardly turned methylcytosine in the duplex region
      owing to the large antibody size. In contrast, the methylcytosine in the bulge is
      recognized by the antibody because it is available to rotate freely owing to the
      single bond between deoxyribose and phosphate in a DNA chain. By employing the
      difference between the affinity in the bulge and that in the duplex, we could
      determine selectively whether or not the target cytosine was methylated in an
      O(6)-methylguanine DNA methyltransferase (MGMT) promoter sequence with a single
      base level. The proposed bulge-specific assay technique can be combined with a
      widely used absorbance measurement method that employs the color change in
      tetramethyl benzidine induced by horseradish peroxidase-labeled secondary
      antibody. The sequence-selective discrimination of the methylation status could
      also be obtained with various types of interfering genomic DNA contamination
      without any conventional bisulfite treatment, polymerase chain reaction, (PCR) or
      electrophoresis.

PMID- 22880798
TI  - Reversible formation of ammonium persulfate/sulfuric acid graphite intercalation
      compounds and their peculiar Raman spectra.
AB  - Graphite intercalation compounds (GICs) can be considered stacks of individual
      doped graphene layers. Here we demonstrate a reversible formation of sulfuric
      acid-based GICs using ammonium persulfate as the chemical oxidizing agent. No
      covalent chemical oxidation leading to the formation of graphite oxide occurs,
      which inevitably happens when other compounds such as potassium permanganate are
      used to charge carbon layers. The resulting acid/persulfate-induced stage-1 and
      stage-2 GICs are characterized by suppression of the 2D band in the Raman spectra
      and by unusually strong enhancement of the G band. The G band is selectively
      enhanced at different doping levels with different excitations. These
      observations are in line with recent reports for chemically doped and gate
      modulated graphene and support newly proposed theories of Raman processes. At the
      same time GICs have some advantageous differences over graphene, which are
      demonstrated in this report. Our experimental observations, along with earlier
      reported data, suggest that at high doping levels the G band cannot be used as
      the reference peak for normalizing Raman spectra, which is a commonly used
      practice today. A Fermi energy shift of 1.20-1.25 eV and ~1.0 eV was estimated
      for the stage-1 and stage-2 GICs, respectively, from the Raman and optical
      spectroscopy data.

PMID- 22880799
TI  - Validation of diethoxyphosphonate as an effective agent for charge transfer in
      Anion Relay Chemistry (ARC).
AB  - The diethoxyphosphonate group comprises an effective agent to achieve negative
      charge migration in Type II Anion Relay Chemistry (ARC). The process involves a
      [1,4]-phosphorus-Brook rearrangement that proceeds via a phosphacyclic
      intermediate leading to an anion that can be captured by reactive electrophiles.
      In the absence of an exogenous electrophile, the anion derived via phosphorus
      migration undergoes internal displacement of the phosphonate group to produce a
      diastereomeric mixture of cyclopropanes.

PMID- 22880800
TI  - Chemical composition and anti-inflammatory and antioxidant activities of eight
      pear cultivars.
AB  - The contents of total phenolics, total flavonoids, total anthocyanins, and total
      triterpenes of eight pear samples were determined, and the monomeric compounds
      were identified and quantitated using high-performance liquid chromatography. The
      in vitro antioxidant and in vivo anti-inflammatory activities of the different
      pear cultivars were compared. Arbutin and catechin were the dominant polyphenol
      compounds in the eight pear varieties, followed by chlorogenic acid, quercetin,
      and rutin. In addition, Xuehua pear and Nanguo pear had significantly higher
      total phenolics and flavonoids contents, while Dangshansu pear had the largest
      total triterpenes value (209.2 mg/100 g). Xuehua pear and Nanguo pear also were
      the highest in total anthocyanins. The pears with high total phenolics and total
      flavonoids contents had significantly higher antioxidant and anti-inflammatory
      abilities than those of other species. Anthocyanins were correlated to
      antioxidant capacity in pears, whereas total triterpenoids were strongly
      correlated to anti-inflammatory activity.

PMID- 22880801
TI  - Platelet glycoprotein IIb HPA-3 a/b polymorphism is associated with native
      arteriovenous fistula thrombosis in chronic hemodialysis patients.
AB  - OBJECTIVE: The aim of this study was to investigate the association of
      Glycoprotein IIb (GPIIb) human platelet antigen-3 (HPA-3) a/b polymorphism with
      end-stage renal disease (ESRD) on hemodialysis (HD) and native Arteriovenous
      fistula (AVF) thrombosis. METHODS: The polymorphism in the GPIIb subunit of the
      receptor HPA-3 (a and b alleles) was identified by polymerase chain reaction with
      sequence-specific primers (PCR-SSP) in 145 HD patients and 120 healthy controls
      from a Chinese Han population. The HD patients were classified into two groups:
      G1 and G2. G1 included 65 HD patients presented at least one AVF thrombosis
      episode and G2 included 80 HD patients without any episode of AVF thrombosis.
      RESULTS: There were no significant differences in either HPA-3 a/b genotypes (aa,
      ab, and bb) frequency distribution (p = 0.396) or allele (a and b) frequency
      distribution (p = 0.146) between HD patients and control groups. However, there
      were significant differences in both HPA-3 a/b genotypes (aa, ab, and bb)
      distribution (chi(2) = 6.127, p = 0.047) and allele (a and b) frequency
      distribution (chi(2) = 5.954, p = 0.015) between G1 and G2. The relative risk of
      native AVF dysfunction in ab + bb patients compared with that of aa patients was
      2.31 (95% confidence interval: 1.18-4.52). CONCLUSIONS: These findings suggest an
      association between AVF thrombosis and the HPA-3b allele, and it is likely that
      HPA-3 a/b polymorphisms could be useful markers for potential risk of native AVF
      thrombosis in HD patients.

PMID- 22880802
TI  - High prevalence of vitamin D insufficiency in southern Chinese renal transplant
      recipients.
AB  - Vitamin D deficiency is common globally. There is evidence that vitamin D status
      may be related to immune function and cardiovascular disease. The vitamin D
      status of Chinese kidney transplant recipients has never been investigated. We
      performed a cross-sectional study and measured the level of 25-hydroxyvitamin D
      [25(OH)D] in 94 Chinese renal transplant recipients with stable allograft
      function. Vitamin D deficiency and insufficiency were detected in 43.6% and 54.2%
      of patients, respectively. About 53.2% of the patients also had elevated
      parathyroid hormone (PTH) levels. The level of 25(OH)D was lower in kidney
      transplant recipients compared with healthy controls matched for age and sex
      (52.5 +/- 15.6 nmol/L vs. 57.5 +/- 19.0 nmol/L, p = 0.05), but the level of serum
      creatinine was higher in kidney transplant recipients (120.3 +/- 48.5 MUmol/L and
      78.3 +/- 15.3 MUmol/L, p < 0.01). The level of 25(OH)D was negatively correlated
      with that of PTH (p = 0.001). The latter was associated with serum creatinine (p
      = 0.001) and duration of dialysis (p = 0.001). Patients with a history of acute
      rejection showed lower levels of 25(OH)D (45.3 +/- 11.9 nmol/L vs. 54.2 +/- 16.0
      nmol/L, p = 0.003). We conclude that vitamin D deficiency is prevalent among
      Chinese renal transplant recipients. In view of the potential immunomodulatory
      effect of vitamin D, the relationship between vitamin D level and rejection and
      the effect of vitamin D supplementation in renal transplant recipients warrant
      further investigations.

PMID- 22880803
TI  - Clinical features of Chinese coronary heart disease patients with chronic kidney
      disease.
AB  - OBJECTIVES: To investigate the prevalence of chronic kidney disease (CKD) by
      stage in Chinese patients with coronary heart disease (CHD) and to identify the
      clinical features and examine control of cardiovascular risk factors. METHODS AND
      RESULTS: Clinical data of hospitalized patients were collected by investigators
      in China. CKD stages were classified according to estimated glomerular filtration
      rate (eGFR). A total of 2509 participants with CHD were included in the final
      statistical analysis. The overall prevalence of CKD stage 3 and greater (eGFR of
      less than 60 mL/min/1.73 m(2)) in the CHD patients was 32.5%. As the CKD stage
      increased, fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and high-sensitivity C-reactive protein (HS-CRP) levels all
      worsened. As the CKD stage became more severe, CHD patients had comorbidities
      such as diabetes mellitus, periphery arterial disease, and ischemic stroke, and
      more CHD patients had triple vessel disease increased. Even when patients
      received treatment of CHD and risk factors, control of cardiovascular risk
      factors such as SBP, DBP, FBG, and low-density lipoprotein was worsened as CKD
      stage became more severe over a 6-week follow-up. CONCLUSIONS: The data suggested
      a high prevalence of CKD in Chinese patients with CHD. Many conventional risk
      factors and comorbidities were correlated with high prevalence of CKD in CHD
      patients. Control of cardiovascular risk factors in those patients was poor.

PMID- 22880804
TI  - The protective effect of ebselen on radiocontrast-induced nephrotoxicity.
AB  - AIM: Radiocontrast-induced nephropathy has become one of the most important
      causes of renal acute failure. The most effective management of reducing the
      incidence of contrast nephropathy is to understand and prevent its causes. We
      aimed to investigate the protective role of ebselen against radiocontrast-induced
      nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light
      microscopy in rats. METHODS: Albino Wistar rats were randomly separated into four
      groups. The Group 1 rats were treated with sodium chloride as the control group,
      Group 2 with radiocontrast, Group 3 with radiocontrast plus ebselen, and Group 4
      with ebselen alone. After 24 h, the animals over the experimental period were
      euthanized and blood samples were analyzed for blood urea nitrogen (BUN) and
      serum creatinine (Cr) levels. Kidney sections were analyzed for malondialdehyde
      (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GSH-Px) activities, as well as histopathological changes. RESULTS: In
      the radiocontrast group, BUN, MDA, and GSH-Px levels increased while SOD activity
      decreased compared with the control group. These decays were improved by ebselen
      administration in the radiocontrast group. Significant histological
      deteriorations were observed in the radiocontrast group. We noted improvement in
      the histologic findings with ebselen administration. CONCLUSION: These results
      indicate that ebselen might produce a protective mechanism against radiocontrast
      induced nephrotoxicity.

PMID- 22880805
TI  - The efficacy of prophylactic antibiotics administration prior to insertion of
      tunneled catheter in hemodialysis patients.
AB  - AIM AND BACKGROUND: Central venous catheter (CVC)-related blood stream infection
      is a major cause of morbidity and mortality in patients with end-stage renal
      diseases. However, CVCs are quite frequently required for vascular access in
      hemodialysis (HD) patients. Tunneled catheters (TCs) are widely used when a
      catheter is needed for a long period. However, long-term catheter survival is
      limited by TC-related infections. The purpose of this prospective study was to
      assess clinical outcomes of prophylactic antibiotics administration prior to
      insertion of TCs in HD patients. MATERIAL AND METHODS: Sixty uremic patients who
      required TC insertion due to vascular access failure were included in our study
      between April 2009 and April 2010. Patients were randomized into two groups:
      group I and group II. Group I received 1 g of cefazolin sodium intravenously 1 h
      prior to catheter insertion. Group II received equal amount of saline
      intravenously 1 h prior to catheter insertion. The primary end points of the
      study were catheter loss, hospitalization, or mortality due to catheter-related
      infections (CRIs). The secondary end points included exit-site infection (not
      requiring hospitalization), tunnel infections (not requiring catheter removal),
      and bacteremia. RESULTS: During the follow-up period, one patient in group I and
      three patients in group II reached primary end point (p < 0.05). Catheter loss
      due to infection was higher in group II than in group I as 6 versus 3,
      respectively (p < 0.05). Catheter exit-site infections, which does not require
      hospitalization, have been considered as secondary end points and have been
      detected in four patients for 7 times in group I and in six patients for 10 times
      in group II (p < 0.05). Tunnel infection, which does not require removal of the
      catheter, has been detected in two patients for 3 times in group I and in five
      patients for 6 times in group II (p < 0.05). CONCLUSION: The prophylactic
      antibiotic use prior to TC insertion significantly reduced CRIs, bacteremia, and
      catheter loss.

PMID- 22880806
TI  - Peripheral arterial disease predicts overall and cardiovascular mortality in
      peritoneal dialysis patients.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is an important manifestation of
      systemic atherosclerosis and is common among dialysis patients. Cardiovascular
      disease (CVD) accounts for the leading cause of mortality in dialysis patients,
      and PAD has been found as a predictor for cardiovascular as well as overall
      mortality in general population. However, the study on the role of PAD in the
      prognosis of peritoneal dialysis patients is rather limited. METHODS: Prevalent
      continuous ambulatory peritoneal dialysis patients over 60 years old were
      recruited in this study and were followed-up regularly to death or the end of the
      study. The diagnosis of PAD was based on ankle-brachial pressure index (ABI) <
      0.9 or intermittent claudication. Univariate and multivariate Cox proportional
      hazard models were used to identify the risk factors for cardiovascular and
      overall mortality. Survival curves were estimated by the Kaplan-Meier method
      followed by log-rank test to compare the mortality rate between PAD and non-PAD
      patients. RESULTS: One hundred and seventy-one patients were included and 62
      (36%) had PAD complication. In the follow-up of 24.4 (median 34.6) months, 36
      deaths were recorded: 19 from PAD group and 17 from non-PAD group. Twenty-one
      patients died due to CVD: 13 from PAD group and 8 from non-PAD group. The
      presence of PAD and serum albumin was found independently associated with
      cardiovascular and overall mortality using Cox proportional hazards model.
      CONCLUSION: PAD is very common in aged peritoneal dialysis patients and
      independently associated with both cardiovascular and overall mortality.

PMID- 22880807
TI  - The performance of acute peritoneal dialysis treatment in neonatal period.
AB  - The aim of this retrospective study was to evaluate our neonatal intensive care
      unit (NICU) patients' characteristics treated with acute peritoneal dialysis (PD)
      and their risk factors for mortality. We also wanted to share our experience of
      the application of PD in neonates who required less than 60 mL of dwell volume
      and their PD-related problems, as well as special solutions for these problems.
      This study included 27 infants treated in our NICU between February 2008 and
      December 2011. We retrospectively analyzed these patients' records. The
      percutaneous PD catheter was placed by us. PD procedure was performed either by
      manual technique or automated PD. Statistical evaluation was performed by using
      chi(2)-tests and Student's t-tests. In these 27 neonates, the average gestational
      age and birth weight were 35.18 +/- 4.02 weeks and 2534.62 +/- 897.41 g,
      respectively. The mean PD duration time was 6.11 +/- 6.30 days. Of these, 10
      patients were treated by manual technique, whereas 17 patients were treated with
      automated system. Among 27 neonates, 16 patients died. Overall mortality rate was
      59.25%. PD-related complications were seen in 25.92% of patients. In conclusion,
      PD application is less effective and troublesome for low-birth-weight infants.
      Each center should create its own solutions to accommodate problematic patients
      in PD treatment to improve the outcome in this special population.

PMID- 22880808
TI  - Chronic renal failure impacts the expression of ghrelin and its receptor in
      hypothalamus and hippocampus.
AB  - BACKGROUND/AIMS: Ghrelin plays a central role in the regulation of
      gastrointestinal (GI) motility. This study aimed to investigate the expression of
      ghrelin and growth hormone secretagogue receptor (GHSR) in the central nervous
      system of rats with chronic renal failure (CRF). METHODS: Sprague-Dawley rats
      (male, 180 +/- 20 g, n = 24) were treated by 5/6 nephrectomy to construct CRF
      model. As their plasma creatinine concentration and blood urea nitrogen were
      maintained more than double the normal level for 2 weeks, they were killed for
      assessing the expression of ghrelin and GHSR in hypothalamus and hippocampus
      using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). The
      rats (male, 180 +/- 20 g, n = 24) treated by Sham operation served as a control.
      One-way analysis of variance and Student-Newman-Keuls q test were used to analyze
      group difference and a p-value of <0.05 was considered as statistically
      significant. RESULTS: Compared with the controls, the ghrelin and GHSR expression
      was obviously increased in the hippocampus (p < 0.05) but decreased in the
      hypothalamus of rats with CRF (p < 0.05). CONCLUSIONS: CRF was found to impact
      the expression of ghrelin and GHSR in hypothalamus and hippocampus. This might be
      associated with the CRF-induced GI motility dysfunction.

PMID- 22880809
TI  - Development of refractory ascites during amiodarone therapy in a hemodialysis
      patient with nephrogenic and cardiogenic ascites.
AB  - In this report, the clinical characteristics of a 65-year-old female patient with
      tricuspid regurgitation, ischemic cardiomyopathy, congestive heart failure, and
      chronic renal failure were retrospectively evaluated. Laboratory studies revealed
      cardiogenic ascites coincided with nephrogenic ascites and subclinical amiodarone
      induced hypothyroidism. The ascites of the patient was responsive to management
      of congestive heart failure and therapeutic paracentesis during the first
      episode, add-on therapy with intensified hemodialysis during the second episode,
      and add-on therapy with low-dose eltroxin during the third episode. When
      nephrogenic ascites and cardiogenic ascites of maintenance hemodialysis patients
      become refractory, hypothyroidism should be examined in these patients.

PMID- 22880810
TI  - Spontaneous perirenal hemorrhage in end-stage renal disease treated with
      selective embolization.
AB  - Spontaneous nontraumatic rupture of the kidney (Wunderlich syndrome) is an
      extremely uncommon condition on hemodialysis. We report a case of 44-year-old
      hemodialysis patient presented with hemorrhagic shock and a right quadrant
      abdominal pain to the emergency department. There was no history of trauma. A
      kidney rupture was revealed by abdominal computed tomography, and active bleeding
      was successfully managed with arterial embolization. This case illustrates the
      safe and successful application of interventional radiology in the management of
      nontraumatic renal hemorrhage in the specific group of hemodialyzed patients even
      in the emergency setting.

PMID- 22880811
TI  - Anuric acute renal failure associated with pericardial effusion without signs of
      cardiac tamponade.
AB  - This article describes the anuric acute renal failure (ARF) secondary to massive
      pericardial effusion without tamponade in an 84 year-old man. He was referred to
      our emergency room with progressive dyspnea and azotemia. An electrocardiogram
      showed sinus tachycardia. A two-dimensional echocardiogram confirmed the presence
      of severe pericardial effusion without prominent ventricular diastolic collapse
      and there were no changes in his vital signs. Laboratory findings showed that his
      blood urea nitrogen and serum creatinine levels were 91.8 and 3.77 mg/dL,
      respectively. Renal ultrasonography showed no signs of hydronephrosis. Urine
      output did not increase in spite of giving a saline and furosemide infusion but
      increased immediately after pericardiocentesis with drainage. His renal function
      was completely restored 3 days after the procedure. A pericardial biopsy
      demonstrated invasion of malignant cells. We should keep in mind that pericardial
      effusion is one of the causes of anuric ARF, although it is not accompanied by
      tamponade.

PMID- 22880812
TI  - Relationship between GSTM1/GSTT1 null genotypes and renal cell carcinoma risk: a
      meta-analysis.
AB  - The results from the published studies on the relationship between GSTM1/GSTT1
      null genotypes and renal cell carcinoma (RCC) risk are still conflicting. This
      meta-analysis was performed to evaluate the relationship between GSTM1/GSTT1 null
      genotypes and RCC susceptibility. Association studies were identified from the
      databases of PubMed, Embase, Cochrane Library, and CBM-disc (China Biological
      Medicine Database) on 1 February 2012, and eligible investigations from 1950 to
      2012 were synthesized using meta-analysis method. Results were expressed as odds
      ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also
      calculated. Six studies were identified for the analysis of association between
      polymorphic deletion of GSTM1/GSTT1 and RCC risk. There was no association
      between GSTM1/GSTT1 null genotype and RCC susceptibility (GSTM1: N = 6, p
      heterogeneity = 0.07, OR = 1.07, 95% CI: 0.85-1.35, p = 0.57; GSTT1: N = 6, p
      heterogeneity < 0.00001, OR = 0.98, 95% CI: 0.58-1.65, p = 0.94). Interestingly,
      null genotype of GSTT1 was associated with RCC risk in Caucasians and Asians
      (Caucasians: N = 4, p-heterogeneity = 0.38, OR = 0.76, 95% CI: 0.61-0.95, p =
      0.01; Asians: N = 1, OR = 2.39, 95% CI: 1.63-3.51, p < 0.00001). For the GSTM1
      GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was not
      significantly associated with RCC susceptibility (N = 4, p-heterogeneity = 0.006,
      OR = 1.17, 95% CI: 0.98-1.39, p = 0.09). However, the dual null genotype of GSTM1
      GSTT1 was associated with RCC risk in Asians (N = 1, OR = 2.06, 95% CI: 1.36
      3.13, p = 0.007). In conclusion, our study results suggest that GSTT1 null
      genotype is associated with the RCC susceptibility in Caucasians and Asians, and
      the dual null genotype of GSTM1-GSTT1 is associated with RCC risk in Asians.
      However, more genetic epidemiological investigations are required to further
      explore this relationship.

PMID- 22880813
TI  - Targeting tetraspanins in cancer.
AB  - INTRODUCTION: Tetraspanins are a family of small proteins that cross the membrane
      four times and form complexes by interacting between themselves and with a
      variety of transmembrane and cytosolic proteins, building a network of
      interactions referred to as tetraspanin web or tetraspanin enriched microdomains
      (TEMs). These domains provide a signaling platform involved in many important
      cellular functions and malignant processes. AREAS COVERED: The authors describe
      the methods and the rationale for targeting tetraspanins in the therapy of cancer
      in this review. EXPERT OPINION: Targeting tetraspanins in cancer may be a
      promising therapy due to the importance of tetraspanins in several steps of tumor
      formation, communication with the environment, dissemination, and metastasis.

PMID- 22880814
TI  - Factors affecting sunscreen use and sun avoidance in a U.S. national sample of
      organ transplant recipients.
AB  - BACKGROUND: Organ transplant recipients have an increased risk of nonmelanoma
      skin cancers due to immunosuppressive therapy following transplantation. Use of
      sunscreen has been shown to reduce this risk. OBJECTIVES: To identify patient and
      healthcare factors associated with sun-protective behaviours in organ transplant
      recipients after transplantation with the goal of increasing overall sunscreen
      use. METHODS: This study utilized a cross-sectional, retrospective survey from a
      national sample of 198 organ transplant recipients in the U.S.A. from 2004 to
      2008 with no prior diagnosis of skin cancer. The main outcome measures were
      sunscreen use and sun avoidance before and after transplantation. Frequency of
      sunscreen use and sun exposure was obtained by self-report on Likert scales
      ranging from never to always, and these responses were converted to a numerical
      scale from 0 to 4. RESULTS: Overall sunscreen use increased after transplantation
      (from a score of 1.4 to 2.1, P < 0.001). Sex, Fitzpatrick skin type, receiving
      advice to avoid sun from a healthcare provider, and pretransplantation sunscreen
      use were significantly associated with frequency of post-transplantation
      sunscreen use in multivariate models. Pretransplantation sun exposure, advice to
      avoid sun and pretransplantation sunscreen use were significantly associated with
      sun avoidance post-transplantation. CONCLUSIONS: Both patient features and
      clinician advice are associated with sun-protective behaviours after organ
      transplantation. These results will help physicians target expanded sun
      protection counselling to those patients most in need of such intervention.

PMID- 22880815
TI  - Family meals and child academic and behavioral outcomes.
AB  - This study investigates the link between the frequency of family breakfasts and
      dinners and child academic and behavioral outcomes in a panel sample of 21,400
      children aged 5-15. It complements previous work by examining younger and older
      children separately and by using information on a large number of controls and
      rigorous analytic methods to discern whether there is causal relation between
      family meal frequency (FMF) and child outcomes. In child fixed-effects models,
      which controlled for unchanging aspects of children and their families, there
      were no significant (p<.05) relations between FMF and either academic or
      behavioral outcomes, a novel finding. These results were robust to various
      specifications of the FMF variables and did not differ by child age.

PMID- 22880816
TI  - Maximizing net extraction using an injection-extraction well pair in a coastal
      aquifer.
AB  - In this study, we examine the maximum net extraction rate from the novel
      arrangement of an injection-extraction well pair in a coastal aquifer, where
      fresh groundwater is reinjected through the injection well located between the
      interface toe and extraction well. Complex potential theory is employed to derive
      a new analytical solution for the maximum net extraction rate and corresponding
      stagnation-point locations and recirculation ratio, assuming steady-state, sharp
      interface conditions. The injection-extraction well-pair system outperforms a
      traditional single extraction well in terms of net extraction rate for a broad
      range of well placement and pumping rates, which is up to 50% higher for an
      aquifer with a thickness of 20 m, hydraulic conductivity of 10 m/d, and fresh
      water influx of 0.24 m(2) /d. Sensitivity analyses show that for a given fresh
      water discharge from an inland aquifer, a larger maximum net extraction is
      expected in cases with a smaller hydraulic conductivity or a smaller aquifer
      thickness, notwithstanding physical limits to drawdown at the pumping well that
      are not considered here. For an extraction well with a fixed location, the
      optimal net extraction rate linearly increases with the distance between the
      injection well and the sea, and the corresponding injection rate and
      recirculation ratio also increase. The analytical analysis in this study provides
      initial guidance for the design of well-pair systems in coastal aquifers, and is
      therefore an extension beyond previous applications of analytical solutions of
      coastal pumping that apply only to extraction or injection wells.

PMID- 22880817
TI  - p53 searches on DNA by rotation-uncoupled sliding at C-terminal tails and
      restricted hopping of core domains.
AB  - The tumor suppressor p53 is a transcription factor that searches its cognate
      sites on DNA. During the search, the roles and interplay of its two DNA binding
      domains, the folded core domain and the disordered C-terminal domain (CTD), have
      been controversial. Here, we performed molecular simulations of p53 at various
      salt concentrations finding that, at physiological salt concentration, p53
      diffuses along nonspecific DNA via rotation-uncoupled sliding with its CTD,
      whereas the core domain repeats dissociation and association. This is in perfect
      agreement with a recent single molecule experiment. In the simulation of
      tetrameric full-length p53, two DNA binding domains both bound to nonspecific DNA
      in a characteristic form at low salt concentration, whereas at physiological salt
      concentration, only CTD kept bound to DNA and the core domain frequently hopped
      on DNA. Simulations of a construct that lacks the core domain (TetCD) clarified
      rotation-uncoupled diffusion on nonspecific DNA. At low salt concentration, the
      diffusion constant due to sliding was dependent on the salt concentration, which
      differs from the prediction of a classic theory of transcription factors. At
      physiological salt concentration, it was independent of the salt concentration,
      in harmony with experiments. Moreover, we found that the sliding via the CTD
      follows the helical pitch of DNA (i.e., rotation-coupled sliding) at low salt
      concentration while it is virtually uncoupled to the helical pitch, a hallmark of
      rotation-uncoupled sliding at physiological salt concentration.

PMID- 22880818
TI  - Relationship between oral health-related quality of life, oral health,
      socioeconomic, and general health factors in elderly Brazilians.
AB  - OBJECTIVES: To assess the impact of oral health on quality of life in elderly
      Brazilians and to evaluate its association with clinical oral health measures and
      socioeconomic and general health factors. DESIGN: Cross-sectional study. SETTING:
      Population-based cohort study on health, well-being, and aging. PARTICIPANTS:
      Eight hundred fifty-seven participants representing 588,384 community-dwelling
      elderly adults from the city of Sao Paulo, Brazil. MEASUREMENTS: Self-perceived
      impact of oral health on quality of life was measured using the Geriatric Oral
      Health Assessment Index (GOHAI), with scores categorized as good, moderate, or
      poor, indicating low, moderate, and high degrees of negative impact on quality of
      life, respectively. RESULTS: Nearly half of the individuals had good GOHAI scores
      (44.7% of overall sample, 45.9% of dentate participants, and 43.4% of edentulous
      participants). In the overall sample, those with poor self-rated general health
      and a need for dental prostheses were more likely to have poor and moderate GOHAI
      scores. Individuals with depression were significantly more likely to have poor
      GOHAI scores. No socioeconomic variables were related to the outcome, except self
      perception of sufficient income, which was a protective factor against a poor
      GOHAI score in dentate participants. CONCLUSION: Moderate and high degrees of
      negative impact of oral health on quality of life were associated with general
      health and clinical oral health measures, independent of socioeconomic factors.

PMID- 22880819
TI  - A novel dual-fluorescence strategy for functionally validating microRNA targets
      in 3' untranslated regions: regulation of the inward rectifier potassium channel
      K(ir)2.1 by miR-212.
AB  - Gene targeting by microRNAs is important in health and disease. We developed a
      functional assay for identifying microRNA targets and applied it to the K(+)
      channel K(ir)2.1 [KCNJ2 (potassium inwardly-rectifying channel, subfamily J,
      member 2)] which is dysregulated in cardiac and vascular disorders. The 3'UTR
      (untranslated region) was inserted downstream of the mCherry red fluorescent
      protein coding sequence in a mammalian expression plasmid. MicroRNA sequences
      were inserted into the pSM30 expression vector which provides enhanced green
      fluorescent protein as an indicator of microRNA expression. HEK (human embryonic
      kidney)-293 cells were co-transfected with the mCherry-3'UTR plasmid and a pSM30
      based plasmid with a microRNA insert. The principle of the assay is that
      functional targeting of the 3'UTR by the microRNA results in a decrease in the
      red/green fluorescence intensity ratio as determined by automated image analysis.
      The method was validated with miR-1, a known down-regulator of K(ir)2.1
      expression, and was used to investigate the targeting of the K(ir)2.1 3'UTR by
      miR-212. The red/green ratio was lower in miR-212-expressing cells compared with
      the non-targeting controls, an effect that was attenuated by mutating the
      predicted target site. miR-212 also reduced inward rectifier current and K(ir)2.1
      protein in HeLa cells. This novel assay has several advantages over traditional
      luciferase-based assays including larger sample size, amenability to time course
      studies and adaptability to high-throughput screening.

PMID- 22880820
TI  - The role of thalidomide and placebo for the treatment of cancer-related anorexia
      cachexia symptoms: results of a double-blind placebo-controlled randomized study.
AB  - OBJECTIVES: To determine the effects of thalidomide and placebo on anorexia
      cachexia and its related symptoms, body composition, resting metabolic rate, and
      serum cytokines and their receptors in patients with advanced cancer. METHODS:
      Included in the study were patients with advanced cancer with weight loss greater
      than 5% in 6 months and who reported anorexia, fatigue, and one of the following:
      anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2
      weeks prior or during the study were excluded from the study. Patients were
      randomly assigned to either 100 mg thalidomide or placebo once a day for 14 days.
      The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of
      Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness
      Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep
      Quality Index (PSQI) were utilized, and in addition body composition, Resting
      Energy Expenditure (REE), and serum cytokine levels were assessed. RESULTS: Of
      the 31 patients entered in the study, 15 were assigned to the thalidomide group
      and 16 to the placebo group. However only 21/31 patients were able to complete
      the study. Compared with their baseline values, both the thalidomide and the
      placebo groups showed significant reduction in cytokines. Tumor necrosis factor
      (TNF)-alpha (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and
      interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide
      group. In the placebo group, TNF-alpha (p=0.008), TNFR1 (p=0.005), TNFR2
      (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically
      significant. However, improvement in these symptoms and cytokine levels were not
      significantly different in the thalidomide group compared with the placebo group.
      None of the patients withdrew from the study because of toxicity of either
      thalidomide or placebo. CONCLUSIONS: Based on the poor accrual rate and attrition
      observed in this study, it is important that future research on thalidomide as a
      treatment for cancer-related anorexia-cachexia symptoms (ACS) in patients with
      advanced cancer use less stringent entry criteria and less exhaustive outcome
      measures.

PMID- 22880821
TI  - An investigation of model forensic bone in soil environments studied using
      infrared spectroscopy.
AB  - Infrared spectroscopy has been used to examine changes to bone chemistry as a
      result of soil burial. Pig carcasses were buried as part of a controlled field
      study, and pig bone was used in soil environments established in the laboratory.
      The variables of species type, bone pretreatment, soil type and pH, moisture
      content, temperature, and burial time were investigated. The crystallinity index
      (CI) and the organic and carbonate contents of the bones were monitored. The data
      revealed decreasing trends in the organic and carbonate contents and an increase
      in the CI of the bone with burial time. An acidic soil environment and soil type
      are the factors that have the most influence on bone chemistry as a result of
      burial. The study demonstrates the potential of infrared spectroscopy as a
      straightforward method of monitoring the changes associated with aging of bones
      in a variety of soil environments.

PMID- 22880822
TI  - Our colleague and friend, Jim Cushing.

PMID- 22880823
TI  - The global dynamics of a discrete juvenile-adult model with continuous and
      seasonal reproduction.
AB  - A general discrete juvenile-adult population model with time-dependent birth rate
      and nonlinear survivorship rates is studied. When breeding is continuous, it is
      shown that the model has a unique globally asymptotically stable positive
      equilibrium provided the net reproductive number is larger than one. If it is
      smaller than one, then the extinction equilibrium is globally asymptotically
      stable. When breeding is seasonal, it is shown that there exists a unique
      globally asymptotically stable periodic solution provided the net reproductive
      number is larger than one. When this value is less than one, the population goes
      to extinction. Conditions on the birth rate where the population with seasonal
      breeding survives while the population with continuous breeding becomes extinct
      are provided.

PMID- 22880824
TI  - The basic reproduction number in epidemic models with periodic demographics.
AB  - Patterns of contact in social behaviour and seasonality due to environmental
      influences often affect the spread and persistence of diseases. Models of
      epidemics with seasonality and patterns in the contact rate include time-periodic
      coefficients, making the systems nonautonomous. No general method exists for
      calculating the basic reproduction number, the threshold for disease extinction,
      in nonautonomous epidemic models. However, for some epidemic models with periodic
      coefficients and constant population size, the time-averaged basic reproduction
      number has been shown to be a threshold for disease extinction. We extend these
      results by showing that the time-averaged basic reproduction number is a
      threshold for disease extinction when the population demographics are periodic.
      The results are shown to hold in epidemic models with periodic demographics that
      include temporary immunity, isolation, and multiple strains.

PMID- 22880825
TI  - A comparison of probabilistic and stochastic formulations in modelling growth
      uncertainty and variability.
AB  - We compare two approaches for inclusion of uncertainty/variability in modelling
      growth in size-structured population models. One entails imposing a probabilistic
      structure on growth rates in the population while the other involves formulating
      growth as a stochastic Markov diffusion process. We present a theoretical
      analysis that allows one to include comparable levels of uncertainty in the two
      distinct formulations in making comparisons of the two approaches.

PMID- 22880826
TI  - Scale transition theory with special reference to species coexistence in a
      variable environment.
AB  - Scale transition theory is a mathematical technique for understanding changes in
      population dynamics with changes in spatial or temporal scale. It explains the
      emergence of new properties on large scales from the interaction between
      nonlinearities and variation on small scales. It applies statistical theory for
      averaging nonlinear functions to understanding this interaction. The fundamental
      concepts are most easily illustrated with reference to spatial models where state
      variables on larger spatial scales are simply defined as averages of those on
      smaller scales. Scale transition theory also explains the conceptually difficult
      topic of how species coexistence arises from temporal fluctuations. In this case,
      averages of per capita growth rates over time define long-term population trends
      and outcomes, and these averages are critically affected by interactions between
      nonlinear dynamics and temporal variation in state variables and environmental
      variables. Two general mechanisms of species coexistence, the storage effect and
      relatively nonlinear competitive variance, emerge.

PMID- 22880827
TI  - Effects of immune system diversity and physical variation of immunotypic mixing
      on the dynamics of rabies in bats.
AB  - The ecology and life history of rabies viruses in bats suggest a need for an
      integrated modelling treatment that extends beyond traditional epidemiological
      approaches. We modify our adaptive modelling approach to investigate the effects
      of immune system structure and immunological mixing events on the disease profile
      of the bat colony and subsequently on the dynamics of rabies viruses in bats. Our
      theoretical framework, which is based on individual (intra-host) models of the
      response of the host to a viral challenge and virus-specific disease mechanisms,
      integrates the individual components to provide information about the disease
      structure and the demographic composition of the bat colony. We focus on the
      changes in dynamics at the population level due to two processes: (1)
      immunological diversity in a biological process, reproduction, and (2)
      immunological diversity in a physical-physiological process, migration. The
      results suggest that immunotypic mixing plays a critical role in the disease
      progression within populations and it is an important factor in determining the
      persistence of rabies in exposed bat colonies.

PMID- 22880828
TI  - Morpho-elastodynamics: the long-time dynamics of elastic growth.
AB  - As elastic tissues grow and remodel, they generate stresses that influence their
      mechanical states which influence the way growth proceeds. This complex feedback
      leads to a dynamic evolution of growth and stresses which can be modelled within
      the theory of exact nonlinear elasticity. Here, we first review the different
      theoretical results considering growth laws and then, we present a new approach
      to look at morphoelasticity as a continuous dynamical process. These evolution
      laws lead to new dynamical systems that can be studied by the classical methods
      of dynamical systems theory.

PMID- 22880829
TI  - Quiescence stabilizes predator-prey relations.
AB  - The classical MacArthur Rosenzweig predator-prey system has a stable coexistence
      point or, if either the prey capacity is large or the predator mortality is low,
      a stable limit cycle. The question here is how the stability properties of the
      coexistence point change when the prey or the predator or both can go quiescent.
      It can be shown that a stable equilibrium stays stable, but an unstable
      equilibrium may become stable. The exact stability domain is determined. In
      general, increasing the duration of the quiescent phase of the prey or of the
      predator widens the stability window. Numerical studies show that limit cycles
      shrink when quiescent phases are introduced.

PMID- 22880830
TI  - Dynamics of discrete-time larch budmoth population models.
AB  - The larch budmoth (LBM) population in the Swiss Alps is well known for its
      periodic outbreaks and regular oscillations over several centuries. The
      ecological mechanisms that drive these oscillations, however, have not been
      unambiguously identified, although a number of hypotheses have been proposed. In
      this article, we investigate several LBM resulting from these different
      ecological hypotheses. We first study a leaf quality-moth population model and
      then two moth-parasitoid models. Existence and stability of equilibria are
      investigated and sufficient conditions for which populations can persist are
      derived. We then provide conclusions based on our analysis.

PMID- 22880831
TI  - The role of age structure in the persistence of a chronic pathogen in a
      fluctuating population.
AB  - Small mammal populations exhibit large fluctuations, potentially leading to local
      extinction of specialist pathogens after bottlenecks. Pathogen persistence in
      recovering populations depends on the epidemiological characteristics of the
      hosts that survive the bottlenecks. Sin Nombre virus is a largely asymptomatic
      infection of deer mice, which creates a chronic lifelong infection. Earlier work
      on this virus has shown that males play a key role in pathogen persistence
      through a combination of longer lifespan and higher seroprevalence. Other
      evidence indicates that mouse age could play an equally important role, as older
      mice may have higher survivorship and higher contact rates. We use age structured
      models to examine the relationships among prevalence, age-dependent demographics,
      and age-dependent epidemiology.

PMID- 22880832
TI  - A non-autonomous multi-strain SIS epidemic model.
AB  - In this paper we consider a non-autonomous multi-strain SIS epidemic model with
      periodic coefficients. Reproduction numbers and invasion reproduction numbers are
      derived which agree well with their counterparts usually derived from autonomous
      epidemic models. With conditions on these reproduction numbers typical results
      are obtained, such as the local and global stability of the disease-free
      equilibrium. Existence and uniqueness of a single-strain periodic solution is
      established. Based on conditions on the invasion reproduction numbers, local
      stability of the single-strain periodic solution is shown. In a two-strain
      version of the model, conditions for uniform strong persistence are derived, and
      coexistence of the two strains is established. Coexistence, however, does not
      occur if the transmission rates of the different strains are linearly dependent.

PMID- 22880833
TI  - The logistic, two-sex, age-structured population model.
AB  - In this paper, we introduce the logistic effect into the two-sex population model
      introduced by Hoppensteadt. We address the problem of existence and uniqueness of
      continuous and classical solutions. We first give sufficient conditions for a
      unique continuous solution to exist locally and also globally. Next, the
      existence of classical solutions is established under some mild assumptions on
      the vital rates. Finally, we study the existence of equilibria and give an upper
      bound for the total population at steady state.

PMID- 22880834
TI  - Persistence in a discrete-time stage-structured fungal disease model.
AB  - A discrete-time susceptible and infected (SI) epidemic model, with less than 100%
      vertical disease transmission, for the spread of a fungal disease in a structured
      amphibian host population, is analysed. Criteria for persistence of the
      population as well as the disease are established. Stability results for host
      extinction and for the disease-free equilibrium are presented. Bifurcation theory
      is used to establish existence of an endemic equilibrium.

PMID- 22880835
TI  - Controlling malaria: competition, seasonality and 'slingshotting' transgenic
      mosquitoes into natural populations.
AB  - Forty years after the World Health Organization abandoned its eradication
      campaign, malaria remains a public health problem of the first magnitude with
      worldwide infection rates on the order of 300 million souls. The present paper
      reviews potential control strategies from the viewpoint of mathematical
      epidemiology. Following MacDonald and others, we argue in Section 1 that the use
      of imagicides, i.e., killing, or at least repelling, adult mosquitoes, is
      inherently the most effective way of combating the pandemic. In Section 2, we
      model competition between wild-type (WT) and plasmodium-resistant, genetically
      modified (GM) mosquitoes. Under the assumptions of inherent cost and prevalence
      dependant benefit to transgenics, GM introduction can never eradicate malaria
      save by stochastic extinction of WTs. Moreover, alternative interventions that
      reduce prevalence have the undesirable consequence of reducing the likelihood of
      successful GM introduction. Section 3 considers the possibility of using seasonal
      fluctuations in mosquito abundance and disease prevalence to 'slingshot' GM
      mosquitoes into natural populations. By introducing GM mosquitoes when natural
      populations are about to expand, one can 'piggyback' on the yearly cycle.
      Importantly, this effect is only significant when transgene cost is small, in
      which case the non-trivial equilibrium is a focus (damped oscillations), and
      piggybacking is amplified by the system's inherent tendency to oscillate. By way
      of contrast, when transgene cost is large, the equilibrium is a node and no such
      amplification is obtained.

PMID- 22880836
TI  - Species decline and extinction: synergy of infectious disease and Allee effect?
AB  - Host-parasite models with density-dependent (mass action) incidence and a
      critical Allee effect in host growth can explain both species decline and
      disappearance (extinction). The behaviour of the model is consistent with both
      the novel pathogen hypothesis and the endemic pathogen hypothesis for
      chytridiomycosis. Mathematically, the transition from decline to disappearance is
      mediated by a Hopf bifurcation and is marked by the occurrence of a heteroclinic
      orbit. The Hopf bifurcation is supercritical if intra-specific host competition
      increases with host density at a large power and subcritical if the power is
      small. In the supercritical case, host-parasite coexistence can be at equilibrium
      or periodic; in the subcritical case it is only at equilibrium.

PMID- 22880837
TI  - Age of infection epidemic models with heterogeneous mixing.
AB  - We extend the age of infection epidemic models to populations divided into an
      arbitrary number of subgroups and derive a set of final size relations if there
      are no disease deaths. If there are disease deaths, the final size relations are
      inequalities, but it is possible to obtain bounds for the epidemic size in terms
      of the final size for the corresponding model without disease deaths and the
      disease death rates. If the mixing is proportionate, we obtain an explicit
      expression for the reproduction number of the model. The heterogeneous mixing age
      of infection epidemic model is a unified form that includes general compartmental
      structures and arbitrary distributions of stay in compartments as well as
      heterogeneity of mixing.

PMID- 22880838
TI  - Threshold dynamics of a delayed reaction diffusion equation subject to the
      Dirichlet condition.
AB  - We establish the threshold dynamics of a delayed reaction diffusion equation
      subject to the homogeneous Dirichlet boundary condition when the delayed reaction
      term is non-monotone. We illustrate the main results by two examples, including
      the delayed Nicholson's blowflies diffusion equation.

PMID- 22880839
TI  - Periodic versus constant harvesting of discretely reproducing fish populations.
AB  - We use a single-species discrete-time model to demonstrate changes that
      introduction of the strong Allee mechanism and periodic exploitations have on
      compensatory and overcompensatory stock dynamics through comparison with
      corresponding models that lack such constraints. Periodic and constant
      exploitations simplify complex overcompensatory stock dynamics with or without
      the Allee effect. Both constant and periodic exploitations force a sudden
      collapse to extinction of fisheries systems that exhibit the Allee mechanism.
      However, in the absence of the Allee effect, fisheries systems decline to zero
      smoothly under high exploitation.

PMID- 22880840
TI  - Follow-up of gynecological cancer patients after treatment - the views of
      European experts in gynecologic oncology.
AB  - OBJECTIVE: Follow-up after treatment for gynecological cancer demands large
      resources. There is a lack of evidence of efficacy. The aim of this survey was to
      explore follow-up routines and views on follow-up care among European experts in
      gynecological oncology. DESIGN: Web-based structured survey. SETTING: Survey
      distributed to members of the European Society of Gynecological Oncology (ESGO)
      and the Nordic Society of Gynecologic Oncology (NSGO). POPULATION: The study
      population comprised members of NSGO and ESGO. METHODS: An anonymous e-survey was
      sent with two additional reminders by e-mail through an electronic web-link to
      all members of both societies. MAIN OUTCOME MEASURES: Surveillance routines. The
      clinical experts' evaluation of evidence and view of follow-up in hospitals vs.
      at general practitioners (GPs). RESULTS: The number of visits recommended by a
      majority of the responders was in line with current guidelines. The use of
      surveillance tests varied considerably. Significantly more responders from low
      economy countries preferred conventional hospital follow-up for all patients
      compared with responders from high economy countries, who considered follow-up by
      GPs adequate in low-risk groups (p < 0.001). CONCLUSIONS: Follow-up routines
      after gynecological cancer vary in Europe. According to the majority of the
      responders of this survey targeting European experts in gynecological oncology,
      follow-up by GPs may be an option for low-risk patients. New follow-up routines
      should preferentially be based on prospective trials comparing conventional
      follow-up of gynecological cancer patients with alternative methods of care,
      assessing survival, detection of recurrence, and quality of life.

PMID- 22880841
TI  - PS: pain and sodium channels.

PMID- 22880842
TI  - O2 insertion into group 9 metal-hydride bonds: evidence for oxygen activation
      through the hydrogen-atom-abstraction mechanism.
AB  - A detailed density functional study was performed to examine the reaction of
      mixed-valence dirhodium and diiridium species
      [M(2)(0,II)(tfepma)(2)(CN(t)Bu)(2)(Cl)(2) (1, tfepma = MeN[P(OCH(2)CF(3))(2)](2),
      CN(t)Bu = tert-butyl isocyaninde)] with HCl and oxygen with an interest in
      examining the pathways for oxygen insertion into the intermediate metal hydride
      to form hydroperoxo species. The O(2) hydrogen atom abstraction mechanism for
      both the Rh and Ir was found to be feasible. This is the first time this
      mechanism has been applied to a Rh system and only the second time it has been
      examined for a system other than Pd. The competing trans HCl reductive
      elimination pathway was also examined and found to be greatly dependent on the
      stereochemistry of the starting hydride primarily due to the intermediate formed
      upon the loss of Cl(-). As a result, the reductive elimination pathway was more
      favorable by 11.5 kcal/mol for the experimentally observed Ir stereoisomer, while
      the two pathways were isoenergetic for the other stereoisomer of the Rh complex.
      All findings are consistent with the kinetics study previously performed.

PMID- 22880843
TI  - An assessment of adalimumab efficacy in three Phase III clinical trials using the
      European Consensus Programme criteria for psoriasis treatment goals.
AB  - BACKGROUND: The European Consensus Programme (ECP) established pan-European
      consensus definitions of psoriasis disease severity and treatment goals among 19
      psoriasis experts from European nations. OBJECTIVES: To use the ECP treatment
      goals to retrospectively assess adalimumab efficacy in patients who participated
      in Phase III clinical trials and met ECP criteria for moderate to severe
      psoriasis. METHODS: Three trials were analysed: CHAMPION (n = 108), REVEAL (n =
      814) and BELIEVE (n = 364). Moderate to severe psoriasis was defined as
      Dermatology Life Quality Index (DLQI) score > 10, with either > 10% body surface
      area involvement or Psoriasis Area and Severity Index (PASI) score > 10.
      Treatment goals were achieved with either treatment success (>= 75% PASI score
      reduction) or intermediate response (PASI response >= 50% and < 75%) with DLQI <=
      5. RESULTS: The percentages of patients who achieved treatment goals at week 16
      in CHAMPION, REVEAL and BELIEVE were, respectively, (i) treatment success, 79.3%,
      72.1% and 68.2%; (ii) intermediate response, 1.7%, 5.0% and 5.0%; or (iii) either
      goal, 81.0%, 77.1% and 73.2%. DLQI <= 5 at week 16 was achieved by 70.7%, 70.1%
      and 67.4% of patients, respectively. Differences between the percentages of
      adalimumab- vs. placebo-treated patients achieving treatment success were
      statistically significant (P < 0.001) from week 4 and week 8 of REVEAL and
      CHAMPION, respectively. CONCLUSIONS: Treatment success was achieved by > 93% of
      patients who attained treatment goals. At week 16 > 70% of patients achieved ECP
      treatment goals and met ECP criteria for continued treatment without
      modification. These results support the utility of ECP treatment goals for the
      assessment of therapeutic efficacy in moderate to severe psoriasis.

PMID- 22880844
TI  - Nanosphere templated continuous PEDOT:PSS films with low percolation threshold
      for application in efficient polymer solar cells.
AB  - Nanometer-sized monodisperse polystyrene nanospheres (PS NS) were designed as an
      opal template for the formation of three-dimensionally continuous poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films. The resultant
      films were successfully applied as the anode buffer layer (ABL) to produce highly
      efficient polymer solar cells (PSCs) with enhanced stability. The conductivity of
      the PS NS-PEDOT:PSS films was maintained up to o(PS) = 0.75-0.80, indicating that
      the formation of continuous PEDOT:PSS films using PS NS templates was successful.
      To demonstrate the applicability of the PS NS-PEDOT:PSS film for organic
      electronics, the PS NS-PEDOT:PSS films were used as ABLs in two different PSCs:
      P3HT:PCBM and P3HT:OXCBA. The photovoltaic performances of both PSCs were
      maintained up to o(PS) = 0.8. In particular, the power conversion efficiency of
      the P3HT:OXCBA PSC with a PS NS-PEDOT:PSS ABL (o(PS) = 0.8) was greater than 5%
      and the air stability of the device was significantly enhanced.

PMID- 22880845
TI  - Workplace programmes for HIV and tuberculosis: a systematic review to support
      development of international guidelines for the health workforce.
AB  - The health service sector has a vital role to play in delivering human
      immunodeficiency virus (HIV) and tuberculosis (TB) prevention, treatment and
      care, yet evidence indicates that healthcare workers (HCWs) themselves lack
      adequate access to HIV and TB services. HCWs are also at increased risk from TB
      and other infectious diseases at work, and therefore accessing HIV services is
      particularly important. A systematic review was therefore conducted to inform the
      development of World Health Organization (WHO) guidelines to improve access to
      HIV and TB services, and specifically, to assess the evidence regarding providing
      such services through workplace-based programmes. We identified any study
      published since 1984 that addressed outcomes of interest as defined through multi
      stakeholder consultations, and were related to workplace interventions in (1) the
      healthcare workplace and (2) any workplace that included HIV and/or TB diagnosis
      and/or treatment. Interventions focusing solely on primary prevention with no
      diagnostic or treatment services were excluded, as they were the subject of other
      guidelines. A minimum of two reviewers independently extracted data and assessed
      the articles against pre-set selection criteria; studies were also profiled and
      quality assessed by a minimum of two reviewers. Three studies met these criteria
      specifically for HCWs; all showed a preponderance of positive benefits, with
      minimal negative outcome. Seven studies met these criteria regarding workplace
      HIV and/or TB diagnosis and/or treatment from other sectors, public or private.
      Again, all showed positive results. The paucity of high-quality evidence in this
      field of research was itself an important finding, beckoning further research on
      workplace-based programmes for health workers. Nonetheless, while more well
      designed intervention studies are definitely desirable, providing programmes for
      HCWs to obtain HIV and TB diagnosis and treatment at the workplace is supported
      by the literature and is consistent with the values of the stakeholders,
      justifying the WHO-International Labour Organization-UNAIDS guidelines that
      emerged.

PMID- 22880846
TI  - Cycloaddition reaction of 2-vinylazetidines with benzyne: a facile access to 1
      benzazocine derivatives.
AB  - The cycloaddition reaction of 2-vinylazetidines with benzyne proceeded smoothly
      without a catalyst, and various benzazocine derivatives were isolated in good to
      high yields. The scope of the reaction, as well as the reactions of other arynes,
      has been studied.

PMID- 22880881
TI  - Basigin: a multifunctional membrane protein with an emerging role in infections
      by malaria parasites.
AB  - INTRODUCTION: Malaria is one of the most serious infectious diseases at the
      beginning of the twenty-first century. Various membrane proteins are present in
      Plasmodium falciparum, the principal malaria pathogen. Among them, P. falciparum
      reticulocyte-binding protein homolog 5 (PfRh5) is indispensable for erythrocyte
      invasion, and has become a promising vaccine target. Basigin (CD147, EMMPRIN) has
      been identified as the erythrocyte receptor of PfRh5, and shown to be essential
      for the invasion of multiple strains of the pathogen. AREAS COVERED: Fundamental
      information on basigin is fully described, including structure as a member of the
      immunoglobulin superfamily and function based on its interactions with external
      molecules and with proteins within the same membrane. The involvement of basigin
      in many diseases such as cancer and inflammatory diseases is also described, the
      implication being that anti-basigin therapy might be helpful to treat certain
      illnesses. Finally, PfRh5 as a vaccine candidate is covered, and its interaction
      with basigin is evaluated. EXPERT OPINION: The identification of basigin, a well
      characterized membrane protein, as a receptor essential for malaria infection
      will contribute significantly to prevention and treatment of malaria. As an
      example, anti-basigin therapy can be considered an alternative approach to the
      treatment of drug-resistant malaria.

PMID- 22880883
TI  - Chemotherapy during pregnancy: effect of anthracyclines on fetal and maternal
      cardiac function.
AB  - Chemotherapy and especially anthracyclines are associated to cardiotoxicity. To
      assess this potential risk during pregnancy a clinical case-control trial was
      conducted. Maternal cardiac function, fetal Doppler and fetal cardiac function
      were evaluated before and after chemotherapy. Maternal cardiac function was
      assessed by echocardiography before and after the third cycle of anthracyclines
      and compared with a control group of 10 non-pregnant women matched for age, type
      of cancer and anthracycline treatment. Ten fetuses exposed to chemotherapy were
      compared with 10 control fetuses matched for gestational age and gender.
      Biometry, amniotic fluid index, fetal Doppler and cardiac function were assessed
      before and after each cycle of chemotherapy. In all, 108 fetal ultrasounds scans
      were performed before and after 36 cycles of chemotherapy. Anthracycline exposure
      did not result in acute maternal and fetal cardiac dysfunction in this small
      cohort study.

PMID- 22880882
TI  - Single-shot characterization of enzymatic reaction constants Km and kcat by an
      acoustic-driven, bubble-based fast micromixer.
AB  - In this work we present an acoustofluidic approach for rapid, single-shot
      characterization of enzymatic reaction constants K(m) and k(cat). The
      acoustofluidic design involves a bubble anchored in a horseshoe structure which
      can be stimulated by a piezoelectric transducer to generate vortices in the
      fluid. The enzyme and substrate can thus be mixed rapidly, within 100 ms, by the
      vortices to yield the product. Enzymatic reaction constants K(m) and k(cat) can
      then be obtained from the reaction rate curves for different concentrations of
      substrate while holding the enzyme concentration constant. We studied the
      enzymatic reaction for beta-galactosidase and its substrate (resorufin-beta-D
      galactopyranoside) and found K(m) and k(cat) to be 333 +/- 130 MUM and 64 +/- 8
      s(-1), respectively, which are in agreement with published data. Our approach is
      valuable for studying the kinetics of high-speed enzymatic reactions and other
      chemical reactions.

PMID- 22880884
TI  - Learning about tool categories via eavesdropping.
AB  - Prior research has found that toddlers will form enduring artifact categories
      after direct exposure to an adult using a novel tool. Four studies explored
      whether 2- (N=48) and 3-year-olds (N=32) demonstrate this same capacity when
      learning by eavesdropping. After surreptitiously observing an adult use 1 of 2
      artifacts to operate a bell via a monitor, 3-year-olds returned to the
      demonstrated kind of tool as "for" the task and avoided it for an alternative
      task over 2 days. Two-year-olds performed similarly after eavesdropping on
      someone with more discriminable artifacts via the method of a window rather than
      a monitor. These results demonstrate that toddlers can acquire enduring artifact
      categories after less than 40 s of surreptitious observation.

PMID- 22880885
TI  - Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels.
AB  - The discovery of epigenetic processes as possible pivotal regulatory mechanisms
      in psychiatric diseases raised the question of how psychoactive drugs may impact
      the epigenetic machinery. In the present study we set out to explore the
      specificity and the mode of action of the reported inhibitory effect of the TCA
      (tricyclic antidepressant) amitriptyline on DNMT (DNA methyltransferase) activity
      in primary astrocytes from the rat cortex. We found that the impact on DNMT was
      shared by another TCA, imipramine, and by paroxetine, but not by venlafaxine or
      the mood stabilizers carbamazepine and valproic acid. DNMT activity in
      subventricular neural stem cells was refractory to the action of ADs
      (antidepressants). Among the established DNMTs, ADs primarily targeted DNMT1. The
      reduction of enzymatic DNMT1 activity was neither due to reduced DNMT1 expression
      nor due to direct drug interference. We tested putative DNMT1-inhibitory
      mechanisms and discovered that a known stimulator of DNMT1, the histone
      methyltransferase G9a, exhibited decreased protein levels and interactions with
      DNMT1 upon AD exposure. Adding recombinant G9a completely reversed the AD
      repressive effect on DNMT1 function. In conclusion, the present study presents a
      model where distinct ADs affect DNMT1 activity via G9a with important
      repercussions for possible novel treatment regimes.

PMID- 22880886
TI  - The value of the metabolic syndrome concept in elderly adults: is it worth less
      than the sum of its parts?
AB  - OBJECTIVES: To determine whether the metabolic syndrome (MetS) or its components
      were more closely associated with disease states and inflammation in elderly
      adults. DESIGN: Sydney Memory and Ageing Study. Cross-sectional, observational
      cohort. SETTING: Population-derived, community-dwelling elderly adults.
      PARTICIPANTS: Nine hundred thirty individuals aged 70 to 90. MEASUREMENTS: Age-
      and sex-adjusted odds ratios (ORs) for disease states; fasting circulating
      inflammatory markers and oxidative metabolism byproducts. RESULTS: MetS was
      associated with diabetes mellitus (OR = 4.1, P < .001) and bowel cancer (OR =
      9.1, P = .03) but not in analyses that controlled for component conditions.
      Models containing component conditions had the strongest associations with heart
      disease. Disease associations were improved after addition of component
      conditions to the MetS model. The reverse did not hold: disease associations were
      not improved when MetS was added to the components model. Low high-density
      lipoprotein cholesterol (HDL-C) was independently associated with myocardial
      infarction (OR = 2.32) and angina pectoris (OR = 2.59) (both P < .008). Waist
      circumference was independently associated with cancer (OR = 1.82, P = .008).
      Although MetS was associated with higher C-reactive protein, vascular cell
      adhesion molecule, interleukin-6, amyloid A, homocysteine, and malondialdehyde,
      it explained less than half of the variance of models containing its components.
      CONCLUSION: The observation that MetS is associated with disease states and
      markers of circulating inflammation in the elderly is explained mainly by
      abdominal obesity and low HDL-C. Longitudinal data will further clarify these
      cross-sectional findings that MetS appears to be less than the sum of its parts
      in elderly adults.

PMID- 22880887
TI  - Analysis of alkylresorcinols in cereal grains and products using ultrahigh
      pressure liquid chromatography with fluorescence, ultraviolet, and CoulArray
      electrochemical detection.
AB  - Alkylresorcinols are phenolic lipids, with homologues ranging from C17 to C25,
      found in high concentrations in whole grain wheat and rye, lower concentrations
      in barley, and negligible concentrations in refined wheat flour. The analysis of
      alkylresorcinols is of importance due to their potential as biomarkers of whole
      grain intake and emerging evidence for some biological effects. Present HPLC
      methods have insufficient resolution for accurately quantitating the mix of alkyl
      and alkenylresorcinols found in rye. An ultrahigh-pressure liquid chromatography
      method was developed, and three detection methods (CoulArray (CAED), ultraviolet
      (UV), and fluorescence detection (FD)) were compared for cereal alkylresorcinol
      analysis. The lower limits of quantitation and detection were 50 and 20 pg
      injected, 5 pg and 2 pg injected, and 500 and 1250 pg injected for FD, CAED, and
      UV, respectively. FD and CAED provided similar results, with some bias for higher
      results with FD (<10% difference). UV detection generally resulted in
      overestimation of alkylresorcinol concentrations. The method was applied to
      cereal (15) and cereal product (90) samples mainly from the United States with
      results in the same range as previous methods. The improved resolution with this
      method allows facile analysis of alkylresorcinols from cereal products, including
      minor unsaturated homologues such as those found in rye.

PMID- 22880888
TI  - Electromagnetic-guided neuronavigation for safe placement of intraventricular
      catheters in pediatric neurosurgery.
AB  - OBJECT: Ventricular catheter shunt malfunction is the most common reason for
      shunt revision. Optimal ventricular catheter placement can be exceedingly
      difficult in patients with small ventricles or abnormal ventricular anatomy.
      Particularly in children and in premature infants with small head size,
      satisfactory positioning of the ventricular catheter can be a challenge.
      Navigation with electromagnetic tracking technology is an attractive and
      innovative therapeutic option. In this study, the authors demonstrate the
      advantages of using this technology for shunt placement in children. METHODS:
      Twenty-six children ranging in age from 4 days to 14 years (mean 3.8 years) with
      hydrocephalus and difficult ventricular anatomy or slit ventricles underwent
      electromagnetic-guided neuronavigated intraventricular catheter placement in a
      total of 29 procedures. RESULTS: The single-coil technology allows one to use
      flexible instruments, in this case the ventricular catheter stylet, to be tracked
      at the tip. Head movement during the operative procedure is possible without loss
      of navigation precision. The intraoperative catheter placement documented by
      screenshots correlated exactly with the position on the postoperative CT scan.
      There was no need for repeated ventricular punctures. There were no operative
      complications. Postoperatively, all children had accurate shunt placement. The
      overall shunt failure rate in our group was 15%, including 3 shunt infections
      (after 1 month, 5 months, and 10 months) requiring operative revision and 1
      distal shunt failure. There were no proximal shunt malfunctions during follow-up
      (mean 23.5 months). CONCLUSIONS: The electromagnetic-guided neuronavigation
      system enables safe and optimal catheter placement, especially in children and
      premature infants, alleviating the need for repeated cannulation attempts for
      ventricular puncture. In contrast to stereotactic techniques and conventional
      neuronavigation, there is no need for sharp head fixation using a Mayfield clamp.
      This technique may present the possibility of reducing proximal shunt failure
      rates and costs for hydrocephalus treatment in this age cohort.

PMID- 22880889
TI  - Threatened ventriculostomy shunt exposure: augmenting native soft tissue coverage
      with acellular dermal matrix graft.
AB  - Avoiding threatened ventriculostomy shunt exposure in the pediatric population
      remains a difficult problem for the neurosurgeon and reconstructive surgeon. In
      this case series, the authors present a novel method of augmenting scalp soft
      tissue with acellular dermal matrix (ADM) in patients with a history of
      ventricular shunt revisions. Soft tissue augmentation with ADM successfully
      prevented shunt exposure in 3 patients with a history of shunt revision due to
      impending exposure following conventional techniques.

PMID- 22880890
TI  - Cerebrospinal fluid volume measurements in hydrocephalic rats.
AB  - Object   Experimental data about the evolution of intracranial volume and
      pressure in cases of hydrocephalus are limited due to the lack of available
      monitoring techniques. In this study, the authors validate intracranial CSF
      volume measurements within the lateral ventricle, while simultaneously using
      impedance sensors and pressure transducers in hydrocephalic animals. Methods   A
      volume sensor was fabricated and connected to a catheter that was used as a shunt
      to withdraw CSF. In vitro bench-top calibration experiments were created to
      provide data for the animal experiments and to validate the sensors. To validate
      the measurement technique in a physiological system, hydrocephalus was induced in
      weanling rats by kaolin injection into the cisterna magna. At 28 days after
      induction, the sensor was implanted into the lateral ventricles. After sealing
      the skull using dental cement, an acute CSF drainage/infusion protocol consisting
      of 4 sequential phases was performed with a pump. Implant location was confirmed
      via radiography using intraventricular iohexol contrast administration. Results  
      Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and
      accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum
      measurement error between measured volume and actual volume as assessed by a
      Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and
      intracranial pressure decreased during CSF shunting and increased during
      infusion. Ventricular enlargement consistent with successful hydrocephalus
      induction was confirmed using imaging, as well as postmortem. These results
      indicate that volume monitoring is feasible for clinical cases of hydrocephalus.
      Conclusions   This work marks a departure from traditional shunting systems
      currently used to treat hydrocephalus. The overall clinical application is to
      provide alternative monitoring and treatment options for patients. Future work
      includes development and testing of a chronic (long-term) volume monitoring
      system.

PMID- 22880891
TI  - Transport of siRNA through lipid membranes driven by nanosecond electric pulses:
      an experimental and computational study.
AB  - The use of small interfering RNA (siRNA) is a blossoming technique for gene
      regulation. However, its therapeutic potential is today severely hampered by the
      lack of an efficient means of safely delivering these nucleic acids to the
      intracellular medium. We report here that a single 10 ns high-voltage electric
      pulse can permeabilize lipid vesicles and allow the delivery of siRNA to the
      cytoplasm. Combining experiments and molecular dynamics simulations has allowed
      us to provide the detailed molecular mechanisms of such transport and to give
      practical guidance for the design of protocols aimed at using nanosecond-pulse
      siRNA electro-delivery in medical and biotechnological applications.

PMID- 22880893
TI  - Heritability of pain sensitivity and opioid analgesia.

PMID- 22880894
TI  - Bioeconomic harvesting of a prey-predator fishery.
AB  - This paper deals with the problem of non-selective harvesting of a prey-predator
      system by using a reasonable catch-rate function instead of usual catch-per-unit
      efforthypothesis. Here both the prey and the predator species obey the law of
      logistic growth. We have taken the predator functional response to prey density
      in such a form that each predator's functional response to the prey density
      approaches a constant as the prey population increases. Boundedness of the
      exploited system is examined. The existence of its steady states and their
      stability (local and global) are studied using Eigenvalue analysis. The existence
      of bionomic equilibria has been illustrated using a numerical example. The
      problem of determining the optimal harvesting policy is then solved by using
      Pontryagin's maximum principle.

PMID- 22880895
TI  - The Beverton-Holt model with periodic and conditional harvesting.
AB  - In this theoretical study, we investigate the effect of different harvesting
      strategies on the discrete Beverton-Holt model in a deterministic environment. In
      particular, we make a comparison between the constant, periodic and conditional
      harvesting strategies. We find that for large initial populations, constant
      harvest is more beneficial to both the population and the maximum sustainable
      yield. However, periodic harvest has a short-term advantage when the initial
      population is low, and conditional harvest has the advantage of lowering the risk
      of depletion or extinction. Also, we investigate the periodic character under
      each strategy and show that periodic harvesting drives population cycles to be
      multiples (period-wise) of the harvesting period.

PMID- 22880896
TI  - A scaling analysis in the SIRI epidemiological model.
AB  - For the spatial stochastic epidemic reinfection model SIRI, where susceptibles S
      can become infected I, then recover and remain only partial immune against
      reinfection R, we determine the phase transition lines using pair approximation
      for the moments derived from the master equation. We introduce a scaling argument
      that allows us to determine analytically an explicit formula for these phase
      transition lines and prove rigorously the heuristic results obtained previously.

PMID- 22880897
TI  - Synchrony in tritrophic food chain metacommunities.
AB  - The synchronous behaviour of interacting communities is studied in this paper.
      Each community is described by a tritrophic food chain model, and the communities
      interact through a network with arbitrary topology, composed of patches and
      migration corridors. The analysis of the local synchronization properties (via
      the master stability function approach) shows that, if only one species can
      migrate, the dispersal of the consumer (i.e., the intermediate trophic level) is
      the most effective mechanism for promoting synchronization. When analysing the
      effects of the variations of demographic parameters, it is found that factors
      that stabilize the single community also tend to favour synchronization. Global
      synchronization is finally analysed by means of the connection graph method,
      yielding a lower bound on the value of the dispersion rate that guarantees the
      synchronization of the metacommunity for a given network topology.

PMID- 22880898
TI  - An SIS epidemiology game with two subpopulations.
AB  - There is significant current interest in the application of game theory to
      problems in epidemiology. Most mathematical analyses of epidemiology games have
      studied populations where all individuals have the same risks and interests. This
      paper analyses the rational-expectation equilibria in an epidemiology game with
      two interacting subpopulations of equal size where decisions change the
      prevalence and transmission patterns of an infectious disease. The transmission
      dynamics are described by an SIS model and individuals are only allowed to invest
      in daily prevention measures like hygiene. The analysis shows that disassortative
      mixing may lead to multiple Nash equilibria when there are two interacting
      subpopulations affecting disease prevalence. The dynamic stability of these
      equilibria is analysed under the assumption that strategies change slowly in the
      direction of self-interest. When mixing is disassortative, interior Nash
      equilibria are always unstable. When mixing is positively assortative, there is a
      unique Nash equilibrium that is globally stable.

PMID- 22880899
TI  - The influence of sexually active non-reproductive groups on persistent sexually
      transmitted diseases.
AB  - We describe several population models exposed to a mild life-long sexually
      transmitted disease, i.e. without significant increased mortality among infected
      individuals and providing no immunity/recovery. We then modify these models to
      include non-reproductive groups consisting of those isolated from sexual contact
      and those who are sexually active but infertile due to choice, medical or other
      reasons. We analyse the potential effect on the dynamics of the population. We
      are interested in how the isolated class may curb the growth of the infected
      group while keeping the healthy population at acceptable levels. We also analyse
      the difference between being sexually active and abstained within the non
      reproductive class and its impact on the epidemic reproductive number and the
      nature of the bifurcation around the disease-free equilibrium. We provide a
      comparison with our models introduced in a previous article, which include only
      the isolated from sexual contact class.

PMID- 22880932
TI  - Dermoscopy use by French private practice dermatologists: a nationwide survey.
AB  - BACKGROUND: Dermoscopy is now recognized as an essential tool for discriminating
      melanoma from other pigmented lesions, as corroborated by several robust meta
      analyses. Although it is considered to be widely used in European countries, no
      published data on this topic are available to date, unlike in Australia and the
      U.S.A. OBJECTIVES:  To describe and quantify the use and learning of dermoscopy
      among French private practice dermatologists. METHODS: A questionnaire of 19
      items regarding demographic characteristics, dermoscopy use and training, and
      physician's judgment on dermoscopy was mailed to all French private practice
      dermatologists. Only questionnaires with an answer to the key item, 'Do you use
      dermoscopy?' were taken into account. RESULTS:   Of 3179 mailed questionnaires,
      1611 were returned and 1576 were analysable (49.6%). Most respondents declared
      using dermoscopy (94.6%), using their dermoscope several times a day (82.7%)
      and/or for the diagnosis of nonpigmented lesions (87.7%). Physicians learned
      dermoscopy mainly through books (75.8%) and/or conferences (88.6%); 12.8%
      reported a dedicated university degree. Dermoscopy helps to detect melanoma
      earlier and to perform fewer biopsies according to 86.6% and 74.6%, respectively.
      On multivariate analysis, female sex and age under 45 years were significantly
      associated with higher utilization rate of dermoscopy [odds ratio 1.89, 95%
      confidence interval (CI) 1.15-3.10; and 2.85, 95% CI 1.14-7.11, respectively].
      CONCLUSIONS:   This is the first published nationwide survey of dermoscopy
      practice in Europe. Despite potential classification and/or selection bias, the
      particularly high penetration rate found in our study suggests that dermoscopy is
      now widely accepted by French private practice dermatologists for the routine
      management of both pigmented and nonpigmented lesions.

PMID- 22880933
TI  - In vitro ligament-bone interface regeneration using a trilineage coculture system
      on a hybrid silk scaffold.
AB  - The ligament-bone interface is a complex structure that comprises ligament,
      fibrocartilage, and bone. We hypothesize that mesenchymal stem cells cocultured
      in between ligament and bone cells, on a hybrid silk scaffold with sections
      suitable for each cell type, would differentiate into fibrocartilage. The section
      of scaffold for osteoblast seeding was coated with hydroxyapatite. A trilineage
      coculture system (osteoblasts-BMSCs-fibroblasts) on a hybrid silk scaffold was
      established. RT-PCR results and immunohistochemistry results demonstrated that
      BMSCs cocultured between fibroblasts and osteoblasts had differentiated into the
      fibrocartilaginous lineage. The morphological change was also observed by SEM
      observation. A gradual transition from the uncalcified to the calcified region
      was formed in the cocultured BMSCs from the region that directly interacted with
      fibroblasts to the region that directly interacted with osteoblasts. The role of
      transforming growth factor beta3 (TGF-beta3) in this trilineage coculture model
      was also investigated by supplementing the coculture system with 10 ng/mL TGF
      beta3. The TGF-treated group showed similar results of fibrocartilaginous
      differentiation of BMSCs with coculture group without TGF-beta3 supplement.
      However, no calcium deposition was found in the cocultured BMSCs in the TGF
      treated group. This may indicate TGF-beta3 delayed the mineralization process of
      chondrocytes.

PMID- 22880934
TI  - Boron-mediated nanotube morphologies.
AB  - The "doping" of carbon nanotubes with heteroatoms is an established method of
      controlling their properties. However, variations in heteroatom concentration in
      multiwalled carbon nanotubes (MWCNTs) tend to produce nanotubes with different
      morphologies, and hence varying properties, within the same sample. Electron
      energy loss spectroscopy in conjunction with imaging using a scanning
      transmission electron microscope (STEM) is a powerful tool to precisely map the
      spatial variation and bonding state of heteroatoms, e.g., B, N, P, Si, or
      combinations of these, present in carbon nanotubes exhibiting different
      structures. TEM analysis revealed that B incorporation during MWCNT growth (B
      MWCNTs) results in nanotube morphologies that can be divided into three different
      types. These include core-shell structures possessing a B-rich core of cones and
      a C outer layer, B-containing cone structures, and MWCNTs with an irregular inner
      channel. In situ studies were carried out using Nanofactory() holder experiments
      in order to investigate the properties of individual B-MWCNTs and to show that
      the three types of nanotubes undergo different current-induced breakdown. The
      inhomogeneity in composition, structure, and properties of B-MWCNTs could result
      from the variation in chemical composition and temperature within the furnace,
      and this work highlights the importance of developing synthesis techniques that
      can control the inclusion of heteroatoms into nanotubes.

PMID- 22880935
TI  - Evolving therapeutic paradigms for multiple myeloma: back to the future.
AB  - Multiple myeloma (MM) is an ancient disease, but until the alkylating agent
      melphalan was found to have anti-myeloma properties in the 1950s there was
      virtually no effective therapy. By the late 1960s, extended dosing with melphalan
      and prednisone tripled survival from diagnosis and became the standard of care
      for newly diagnosed MM. "Maintenance therapy" to prolong survival through
      sustained disease control following induction chemotherapy was sought by 1970,
      but early strategies were ineffective and toxic. Subsequent applications of high
      dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment
      paradigm for MM from extended dosing to an intensive strategy designed to
      eradicate the malignant cells in a single course of treatment. Although HDT-ASCT
      resulted in prolonged duration of remission and improved survival, the vast
      majority of patients still relapsed. Interferon (IFN) and glucocorticoid
      maintenance therapies demonstrated marginal improvements in outcomes but
      significant adverse effects. Novel agents introduced over the last decade have
      prolonged survival when given for maintenance following HDT-ASCT, but have also
      challenged the HDT-ASCT paradigm by achieving comparable remission rates when
      used alone as extended frontline therapy. This article reviews the evolution of
      therapeutic strategies for MM and discusses future questions facing MM
      investigators.

PMID- 22880936
TI  - LSD and 9,10-dihydro-LSD analyses in street drug blotter samples via easy ambient
      sonic-spray ionization mass spectrometry (EASI-MS).
AB  - Normally, the identification of the LSD drug is performed by forensic
      laboratories, using the Ehrlich spot test. However, this is a nonspecific
      analysis. Additionally, the Brazilian Federal Police has identified the presence
      of a new compound in seized blotters: 9,10-dihydro-LSD, an uncontrolled
      substance. In this work, easy ambient sonic-spray ionization mass spectrometry in
      the positive ion mode, EASI(+)-MS, was used to characterize LSD and 9,10-dihydro
      LSD compositions directly from the surface of blotters. The presence of LSD in
      the seized blotter samples were also confirmed via high-performance liquid
      chromatography with ultraviolet detector. In a set of 41 blotters analyzed by
      EASI(+)-MS, 28 showed positive results for LSD, seven for 9,10-dihydro-LSD, and
      another six samples showed negative results for both LSD and 9,10-dihydro-LSD.
      The combination of thin layer chromatography with EASI-MS also demonstrated to be
      a relatively simple and powerful screening tool for forensic analysis of street
      drugs.

PMID- 22880937
TI  - (C8H22N4Zn)2Ge7O14(OH)F3: a one-dimensional zinc germanate containing hollow
      columns with an 18-membered window.
AB  - A new zinc germanate incorporating a tetradentate amine ligand has been
      synthesized by the solvothermal method and structurally characterized by single
      crystal X-ray diffraction, solid-state (19)F NMR spectroscopy, thermal analysis,
      and IR spectroscopy. Its structure contains close-packed hollow columns with an
      18-membered window, each of which contains six one-dimensional chains formed of
      Ge(7)X(19) (X = O, OH, F) clusters connected to zinc complexes.

PMID- 22880938
TI  - Interactions binding mineral and organic phases in nanocomposites based on
      bacterial cellulose and calcium phosphates.
AB  - The interactions responsible for the adhesion of calcium phosphate (CP)
      nanocrystals and bacterial cellulose (BC) nanofibrils in the composite material
      obtained by mixing aqueous suspensions of presynthesized CP and BC and the
      dependence of these interactions on the CP morphology and chemical structure have
      been elucidated by molecular mechanics calculations of the CP-BC interfacial
      structures. The interactions between the superficial CP and BC crystal layers
      have been simulated. Two crystalline CP structures (i.e., hydroxyapatite (HAP)
      and whitlockite) with two morphologies (plate-shaped and rod-shaped) were
      considered. Electrostatics has been found to be the major contributor to the
      adhesion of the CP crystallites and BC nanofibers, and the formation of
      interfacial hydrogen bonds makes a minor contribution to the interaction energy.
      It has also been found that, in general, the energy gain resulting from
      whitlockite-BC binding is greater than that for HAP-BC binding, and the binding
      of the rod-shaped crystallites of whitlockite with BC is the most profitable. The
      energy loss and entropy gain upon replacement of the BC-water and CP-water
      contacts by the BC-CP contacts have been estimated.

PMID- 22880939
TI  - Oncolytic virotherapy with modified adenoviruses and novel therapeutic targets.
AB  - INTRODUCTION: Numerous oncolytic viral mutants derived from a variety of strains
      have antitumor efficacy with limited or no toxicity to normal tissue. While all
      modes of administration were determined to be safe in patients with solid cancers
      refractory to current standard of care, this therapeutic approach requires
      further improvements to achieve definite efficacy. AREAS COVERED: We review the
      most promising clinical developments with several oncolytic viruses. The focus is
      on preclinical and clinical findings with replication-selective adenoviral
      mutants including ONYX-015, H101 and Ad5DeltaCR mutants that, to date, are the
      most studied oncolytic viruses. Cellular pathways reported to play a role in
      virus-induced cell killing are reviewed as potential targets for the development
      of more effective combinatorial therapies. EXPERT OPINION: The most promising
      clinical outcomes for metastatic cancers have been reported for oncolytic
      vaccinia and herpes virus mutants expressing the cytokine GMCSF. However, highly
      efficacious and selective adenoviral mutants have been developed that interact
      synergistically with cytotoxic drugs in model systems. We anticipate that by
      delineating the cellular targets for synergistic cancer cell killing in response
      to adenoviral mutants and drugs such as apoptosis and autophagy signaling,
      greatly improved anticancer therapies will result in the near future.

PMID- 22880940
TI  - A different interpretation of Einstein's viscosity equation provides accurate
      representations of the behavior of hydrophilic solutes to high concentrations.
AB  - Viscosities of aqueous solutions of many highly soluble hydrophilic solutes with
      hydroxyl and amino groups are examined with a focus on improving the
      concentration range over which Einstein's relationship between solution viscosity
      and solute volume, V, is applicable accurately. V is the hydrodynamic effective
      volume of the solute, including any water strongly bound to it and acting as a
      single entity with it. The widespread practice is to relate the relative
      viscosity of solute to solvent, eta/eta(0), to V/V(tot), where V(tot) is the
      total volume of the solution. For solutions that are not infinitely dilute, it is
      shown that the volume ratio must be expressed as V/V(0), where V(0) = V(tot) - V.
      V(0) is the volume of water not bound to the solute, the "free" water solvent. At
      infinite dilution, V/V(0) = V/V(tot). For the solutions examined, the
      proportionality constant between the relative viscosity and volume ratio is shown
      to be 2.9, rather than the 2.5 commonly used. To understand the phenomena
      relating to viscosity, the hydrodynamic effective volume of water is important.
      It is estimated to be between 54 and 85 cm(3). With the above interpretations of
      Einstein's equation, which are consistent with his stated reasoning, the relation
      between the viscosity and volume ratio remains accurate to much higher
      concentrations than those attainable with any of the other relations examined
      that express the volume ratio as V/V(tot).

PMID- 22880941
TI  - Relapsed or refractory pediatric acute lymphoblastic leukemia: current and
      emerging treatments.
AB  - Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity
      and mortality in pediatrics. With contemporary chemotherapy, >85% of patients
      with newly diagnosed ALL survive. Unfortunately, 20% of these patients will
      relapse and for these children, outcomes remain poor despite our best known
      chemotherapy protocols. Most of these children will achieve a second complete
      remission, but maintaining this remission remains difficult. Because relapsed ALL
      is such a significant cause of morbidity and mortality, it is the focus of much
      research interest. Efforts have been made and continue to focus on understanding
      the underlying biology that drives relapse. The role of hematopoietic stem cell
      transplantation in relapsed ALL remains unclear, but many clinicians still favor
      this for high-risk patients given the poor prognosis with current chemotherapy
      alone. It is important to use new drugs with little cross-resistance in the
      treatment of relapsed ALL. New classes of agents are currently being studied. We
      also discuss prognostic factors and the biology of relapsed ALL.

PMID- 22880942
TI  - Pharmacokinetics of olmesartan medoxomil in pediatric patients with hypertension.
AB  - BACKGROUND: The prevalence and importance of hypertension in younger patients is
      becoming increasingly recognized; however, only a limited number of clinical
      trials have been conducted in the pediatric population. OBJECTIVE: The aim of
      this study was to characterize the pharmacokinetics and short-term safety of
      olmesartan medoxomil in children and adolescents with hypertension. METHODS: An
      open-label, multicenter, single-dose study was conducted in children and
      adolescents aged 12 months-16 years who were receiving treatment for hypertension
      or, if not currently treated for hypertension, had either a systolic blood
      pressure (SBP) or diastolic blood pressure (DBP).>=95th percentile, or SBP or DBP
      >=90th percentile if diabetic or with a family history of hypertension. Patients
      were stratified by age: 12-23 months (Group 1; none enrolled), 2-5 years (Group
      2; n = 4), 6-12 years (Group 3; n = 10), and 13-16 years (Group 4; n = 10). All
      patients received a single oral dose of olmesartan medoxomil based on the
      individual's age and bodyweight. Patients aged <6 years received an oral
      suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to
      exceed 20 mg), those aged >=6 years who weighed >=35 kg received olmesartan
      medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan
      medoxomil 20 mg tablets. RESULTS: In Groups 2, 3, and 4, the weight-adjusted
      apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 +/- 0.034,
      0.062 +/- 0.020, and 0.072 +/- 0.022 L/h/kg, respectively, and the weight
      adjusted apparent volume of distribution (Vd/F) was 0.32 +/- 0.16, 0.33 +/- 0.14,
      and 0.49 +/- 0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not
      significantly different. Statistical comparisons between Groups 3 or 4 and Group
      2 were not performed due to the small sample size of Group 2 (n = 4). Plasma
      elimination half-life and time to maximum plasma concentration were similar
      across the three groups. In Groups 3 and 4, considerable interindividual
      variability was seen in maximum plasma concentration (C(max)), area under the
      curve (AUC) from time zero to the last measurable concentration, and apparent
      clearance, with AUC and C(max) approximately 30% greater in Group 3. Four of 24
      (16.7%) patients experienced treatment-emergent adverse events that were all mild
      in severity and considered not drug-related. No deaths, serious adverse events,
      or discontinuations due to adverse events occurred in the study. CONCLUSIONS:
      Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic
      profile in pediatric patients similar to that of adults when adjusted for body
      size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00151814

PMID- 22880944
TI  - The role of individual correlates and class norms in defending and passive
      bystanding behavior in bullying: a multilevel analysis.
AB  - This study investigates possible individual and class correlates of defending and
      passive bystanding behavior in bullying, in a sample of 1,825 Italian primary
      school (mean age=10 years 1 month) and middle school (mean age=13 years 2 months)
      students. The findings of a series of multilevel regression models show that both
      individual (e.g., provictim attitudes and perceived peer pressure for
      intervention) and class characteristics (e.g., class provictim attitudes, peer
      injunctive norms, and descriptive norms) help explain defending and passive
      bystanding behavior in bullying. These results significantly expand previous
      findings in this field, by demonstrating the need for a social-ecological
      approach to the study of the different aspects of bullying. Implications for
      antibullying programs are discussed.

PMID- 22880943
TI  - A randomized controlled trial of an HIV/AIDS Symptom Management Manual for
      depressive symptoms.
AB  - Abstract Depressive symptoms are highly prevalent, underdiagnosed, and
      undertreated in people living with HIV/AIDS (PLWH), and are associated with
      poorer health outcomes. This randomized controlled trial examined the effects of
      the HIV/AIDS Symptom Management Manual self-care symptom management strategies
      compared with a nutrition manual on depressive symptoms in an international
      sample of PLWH. The sample consisted of a sub-group (N=222) of participants in a
      larger study symptom management study who reported depressive symptoms.
      Depressive symptoms of the intervention (n=124) and control (n=98) groups were
      compared over three months: baseline, one-month, and two-months. Use and
      effectiveness of specific strategies were examined. Depressive symptom frequency
      at baseline varied significantly by country (chi (2) 12.9; p=0.04). Within the
      intervention group there were significant differences across time in depressive
      symptom frequency [F(2, 207) = 3.27, p=0.05], intensity [F(2, 91) = 4.6, p=0.01],
      and impact [F(2, 252) = 2.92, p= 0.05), and these were significantly lower at one
      month but not at two months, suggesting that self-care strategies are effective
      in reducing depressive symptoms, however effects may be short term. Most used and
      most effective self-care strategies were distraction techniques and prayer. This
      study suggests that people living with HIV can be taught and will employ self
      care strategies for management of depressive symptoms and that these strategies
      are effective in reducing these symptoms. Self-care strategies are noninvasive,
      have no side-effects, and can be readily taught as an adjunct to other forms of
      treatment. Studies are needed to identify the most effective self-care strategies
      and quantify optimum dose and frequency of use as a basis for evidence-based
      practice.

PMID- 22880945
TI  - Improvement in nutritional status reduces the clinical impact of infections in
      older adults.
AB  - OBJECTIVES: To determine the effect of a dietary intervention and micronutrient
      supplementation on self-reported infections in older adults. DESIGN: A
      randomized, placebo-controlled intervention trial. SETTING: Community living
      older people in South Yorkshire, United Kingdom. PARTICIPANTS: Two-hundred
      seventeen older adults aged 65 to 85. INTERVENTION: Participants were randomized
      to a dietary intervention, a daily micronutrient supplement, or placebo for 3
      months, with a 3-month follow-up. MEASUREMENTS: Self-reported measures of
      infection were reported over the 6-month study period. Secondary outcome measures
      were nutritional status, dietary intake, quality of life, and depression.
      RESULTS: Self-reported measures of infection over the 6-month duration of the
      study were significantly different between the treatment groups. The number of
      weeks in which illness affected life and the number of general practitioner and
      hospital visits were significantly lower in the food and micronutrient groups
      than in the placebo group. The number of weeks in which symptoms of an infection
      were described was significantly lower in the food group than the placebo and
      micronutrient groups. Significant improvements in biomarkers of micronutrient
      status were achieved in the food and micronutrient groups and showed
      significantly greater change than observed in the placebo group. Significant
      improvement in dietary intakes was observed in the food group only. CONCLUSION:
      Improving dietary intake and micronutrient status reduces the clinical impact of
      self-reported infections in older adults.

PMID- 22880946
TI  - Interaction of a fresh water lake and a karstic spring via a syncline fold.
AB  - Kaftar Lake is a high-altitude fresh water lake located in High Zagros, south of
      Iran. Despite the high annual evaporation to precipitation ratio in the area,
      lake water electrical conductivity is usually lower than 1000 uS/cm, this may be
      due to high seepage from the floor of the lake. Therefore, the hypothesis of
      possible underground connections between Namdan Basin, where the lake is located,
      and the surrounding basins with lower elevation (Aspas and Dehbid Basins) was
      investigated. Hydrogeology, hydrochemistry, and stable isotopes data of the lake
      and surrounding basins along with the lake water balance study were applied to
      test the hypothesis. Results indicate that Kaftar Lake has no connection with
      Aspas Basin in south, but it is hydraulically connected to Dehbid Basin. In
      Dehbid Basin, "Ghasr_e_Yaghoob spring" (average discharge ?1200 L/s) emerges from
      a small outcrop (about 0.8 km(2) ) of Daryan limestone Formation, where this
      outcrop is much smaller than the required recharge area for such average
      discharge rate. The study shows that this spring is recharged by Kaftar Lake and
      Namdan Basin aquifer, through Daryan Formation of Gandboee Syncline located to
      the northern part of the lake.

PMID- 22880948
TI  - The development of fast-track principles in gynecological surgery.
AB  - Fast-track is a multimodal strategy aimed at reducing the physiological burden of
      surgery to achieve an enhanced postoperative recovery. The strategy combines
      unimodal evidence-based interventions in the areas of preoperative preparation,
      anesthesia, surgical factors and postoperative care. The advantages of fast-track
      most likely extend to gynecology, although so far have scarcely been reported.
      This review summarizes current evidence concerning use of fast-track in general
      and in gynecological surgery. The main findings of this review are that there are
      benefits within elective gynecological surgery, but studies of quality of life,
      patient satisfaction and health economics in elective surgery are needed. Studies
      of fast-track within the field of non-elective gynecological surgery are lacking.
      Widespread education is needed to improve the rate of implementation of fast
      track. Close involvement of the entire surgical team is imperative to ensure a
      structured perioperative care aiming for enhanced postoperative recovery.

PMID- 22880949
TI  - Midfacial Rejuvenation.
AB  - Abstract   N/A.

PMID- 22880947
TI  - Structural context effects in the oxidation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine to hydantoin products: electrostatics, base stacking, and base
      pairing.
AB  - 8-Oxo-7,8-dihydroguanine (OG) is the most common base damage found in cells,
      where it resides in many structural contexts, including the nucleotide pool,
      single-stranded DNA at transcription forks and replication bubbles, and duplex
      DNA base-paired with either adenine (A) or cytosine (C). OG is prone to further
      oxidation to the highly mutagenic hydantoin products spiroiminodihydantoin (Sp)
      and 5-guanidinohydantoin (Gh) in a sharply pH-dependent fashion within
      nucleosides. In the present work, studies were conducted to determine how the
      structural context affects OG oxidation to the hydantoins. These studies revealed
      a trend in which the Sp yield was greatest in unencumbered contexts, such as
      nucleosides, while the Gh yield increased in oligodeoxynucleotide (ODN) contexts
      or at reduced pH. Oxidation of oligomers containing hydrogen-bond modulators (2,6
      diaminopurine, N(4)-ethylcytidine) or alteration of the reaction conditions (pH,
      temperature, and salt) identify base stacking, electrostatics, and base pairing
      as the drivers of the key intermediate 5-hydroxy-8-oxo-7,8-dihydroguanine (5-HO
      OG) partitioning along the two hydantoin pathways, allowing us to propose a
      mechanism for the observed base-pairing effects. Moreover, these structural
      effects cause an increase in the effective pK(a) of 5-HO-OG, following an
      increasing trend from 5.7 in nucleosides to 7.7 in a duplex bearing an OG.C base
      pair, which supports the context-dependent product yields. The high yield of Gh
      in ODNs underscores the importance of further study on this lesion. The
      structural context of OG also determined its relative reactivity toward
      oxidation, for which the OG.A base pair is ~2.5-fold more reactive than an OG.C
      base pair, and with the weak one-electron oxidant ferricyanide, the OG nucleoside
      reactivity is >6000-fold greater than that of OG.C in a duplex, leading to the
      conclusion that OG in the nucleoside pool should act as a protective agent for OG
      in the genome.

PMID- 22880950
TI  - Insight into the mechanism of coffee melanoidin formation using modified "in
      bean" models.
AB  - To study the mechanism of coffee melanoidin formation, green coffee beans were
      prepared by (1) removal of the hot water extractable components (WECoffee); (2)
      direct incorporation of sucrose (SucCoffee); and (3) direct incorporation of type
      II arabinogalactan-proteins (AGPCoffee). As a control of sucrose and AGP
      incorporation, lyophilized green coffee beans were also immersed in water
      (control). The original coffee and the four modified "in bean" coffee models were
      roasted and their chemical characteristics compared. The formation of material
      not identified as carbohydrates or protein, usually referred to as "unknown
      material" and related to melanoidins, and the development of the brown color
      during coffee roasting have distinct origins. Therefore, a new parameter for
      coffee melanoidin evaluation, named the "melanoidin browning index" (MBI), was
      introduced to handle simultaneously the two concepts. Sucrose is important for
      the formation of colored structures but not to the formation of "unknown
      material". Type II AGPs also increase the brown color of the melanoidins, but did
      not increase the amount of "unknown material". The green coffee hot water
      extractable components are essential for coffee melanoidin formation during
      roasting. The cell wall material was able to generate a large amount of "unknown
      material". The galactomannans modified by the roasting and the melanoidin
      populations enriched in galactomannans accounted for 47% of the high molecular
      weight brown color material, showing that these polysaccharides are very relevant
      for coffee melanoidin formation.

PMID- 22880951
TI  - Recognition of need in health care consultations: a qualitative study of people
      with psoriasis.
AB  - BACKGROUND: Psoriasis is a life-long inflammatory condition that can impact on
      quality of life, psychological and social functioning. Previous literature
      suggests patient dissatisfaction with psoriasis management; however, little is
      known about people's specific experiences of health care consultations.
      OBJECTIVES: The study aimed to explore in depth the perspectives of people living
      with psoriasis including coping responses, self-care strategies and how
      consultations with health care professionals in both primary and secondary care
      are experienced. METHODS: Qualitative semistructured interviews were carried out
      with a diverse sample of 29 people with psoriasis generated purposively and
      recruited from community sources in North West England. Interviews were coded
      using Framework Analysis to produce a thematic framework incorporating key
      emerging issues and concepts. RESULTS: Participants experienced psoriasis as a
      complex condition involving physical, psychological and social challenges, as
      well as issues of control, but perceived that these were largely unacknowledged
      by practitioners in health care consultations. Practitioners were perceived as
      lacking knowledge and expertise in the management of psoriasis, lacking empathy
      with the effects of psoriasis and failing to manage it as a long-term condition.
      This perceived lack of support resulted in some participants withdrawing from
      conventional health service providers and seeking alternative sources of help.
      CONCLUSIONS: Psoriasis needs to be recognized and managed as a complex long-term
      condition with emotional and social needs that are addressed alongside
      appropriate diagnosis and regular reviews of treatments which may involve
      referrals to specialist care.

PMID- 22880952
TI  - The protective effect of picroside II against hypoxia/reoxygenation injury in
      neonatal rat cardiomyocytes.
AB  - CONTEXT: Picroside II, an iridoid glucoside found in the root of Picrorhiza
      scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to possess
      potent antioxidant activity. However, whether picroside II has a protective
      effect against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury is poorly
      understood. OBJECTIVE: To explore the cardioprotective role of picroside II
      against oxidative stress induced by H/R injury in neonatal rat cardiacmyocytes.
      MATERIALS AND METHODS: The viability and cellular damage of cardiomyocytes were
      assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide (MTT) and
      lactate dehydrogenase (LDH) assays, respectively. The activities of superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px), the levels of reduced (GSH)
      and oxidized glutathione (GSSG), and the contents of malondialdehyde (MDA) were
      determined by a colorimetric method. The levels of intracellular reactive oxygen
      species (ROS) and calcium were evaluated by flow cytometric analysis. RESULTS: We
      analyzed the effective half-maximal concentration for protection from the dose
      response curves and obtained the concentration of 50 ug/mL as EC(50). Pretreated
      cardiomyocytes with picroside II (50-200 ug/mL), prior to H/R exposure, inhibited
      LDH activity in culture media and increased cell viability in a dose-dependent
      manner. This protective effect was accompanied by significantly increasing
      reduced GSH contents and the activities of SOD and GSH-Px and attenuating MDA and
      GSSG contents in response to H/R injury. Furthermore, treatment with picroside II
      also inhibited ROS production and calcium accumulation in cardiomyocytes.
      DISCUSSION AND CONCLUSION: The present study demonstrates that picroside II
      protects cardiomyocytes against oxidative-stress injury induced by H/R through
      reduction of ROS production and calcium accumulation and enhancement of the
      activity of antioxidant defense.

PMID- 22880953
TI  - Effective treatment of pomalidomide in central nervous system myelomatosis.

PMID- 22880955
TI  - Increasing the multiplexing capacity of TMTs using reporter ion isotopologues
      with isobaric masses.
AB  - Quantitative mass spectrometry methods offer near-comprehensive proteome
      coverage; however, these methods still suffer with regards to sample throughput.
      Multiplex quantitation via isobaric chemical tags (e.g., TMT and iTRAQ) provides
      an avenue for mass spectrometry-based proteome quantitation experiments to move
      away from simple binary comparisons and toward greater parallelization. Herein,
      we demonstrate a straightforward method for immediately expanding the throughput
      of the TMT isobaric reagents from 6-plex to 8-plex. This method is based upon our
      ability to resolve the isotopic shift that results from substituting a (15)N for
      a (13)C. In an accommodation to the preferred fragmentation pathways of ETD, the
      TMT-127 and -129 reagents were recently modified such that a (13)C was exchanged
      for a (15)N. As a result of this substitution, the new TMT reporter ions are 6.32
      mDa lighter. Even though the mass difference between these reporter ion
      isotopologues is incredibly small, modern high-resolution and mass accuracy
      analyzers can resolve these ions. On the basis of our ability to resolve and
      accurately measure the relative intensity of these isobaric reporter ions, we
      demonstrate that we are able to quantify across eight samples simultaneously by
      combining the (13)C- and (15)N-containing reporter ions. Considering the
      structure of the TMT reporter ion, we believe this work serves as a blueprint for
      expanding the multiplexing capacity of the TMT reagents to at least 10-plex and
      possibly up to 18-plex.

PMID- 22880956
TI  - Fabry disease in children: agalsidase-beta enzyme replacement therapy.
AB  - Fabry disease is a rare, multiorgan disease. The most serious complications
      involve the kidney, brain and heart. This study aims to assess the effect of
      enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry
      disease. We carried out a nationwide, descriptive and observational retrospective
      cohort study of 10 children (9-16 years at baseline), who underwent regular
      systematic investigations for 1-8 years after initiation of ERT with agalsidase
      beta (Fabryzyme(r), Genzyme). Ophthalmological, echocardiographic abnormalities
      and hypohidrosis were found at baseline and during the follow-up period. Serious
      kidney, heart or brain involvement had not developed at the last follow-up
      examination. For the majority of the patients improvements were found concerning
      headache, acroparaesthesias and gastrointestinal pain during the follow-up
      period. The level of energy and physical activity also increased. Treatment with
      agalsidase-beta was associated with a reduction of neuropathic and abdominal pain
      and headache. Although all aspects of the Fabry pain phenotype cannot be treated
      with ERT, the observed effects were clinically significant in the lives of the
      majority of Fabry children and together with the absence of serious Fabry
      manifestations at last follow-up, we argue that early initiation of ERT may be
      considered.

PMID- 22880957
TI  - Use of care management practices in small- and medium-sized physician groups: do
      public reporting of physician quality and financial incentives matter?
AB  - OBJECTIVE: To examine the effect of public reporting (PR) and financial
      incentives tied to quality performance on the use of care management practices
      (CMPs) among small- and medium-sized physician groups. DATA: Survey data from The
      National Study of Small and Medium-sized Physician Practices were used. Primary
      data collection was also conducted to assess community-level PR activities. The
      final sample included 643 practices engaged in quality reporting; about half of
      these practices were subject to PR. STUDY DESIGN: We used a treatment effects
      model. The instrumental variables were the community-level variables that capture
      the level of PR activity in each community in which the practices operate.
      FINDINGS: (1) PR is associated with increased use of CMPs, but the estimate is
      not statistically significant; (2) financial incentives are associated with
      greater use of CMPs; (3) practices' awareness/sensitivity to quality reports is
      positively related to their use of CMPs; and (4) combined PR and financial
      incentives jointly affect CMP use to a greater degree than either of these
      factors alone. CONCLUSION: Small- to medium-sized practices appear to respond to
      PR and financial incentives by greater use of CMPs. Future research needs to
      investigate the appropriate mix and type of incentive arrangements and quality
      reporting.

PMID- 22880958
TI  - High level of heterogeneity among Listeria monocytogenes isolates from clinical
      and food origin specimens in Greece.
AB  - In order to examine the genetic variation of clinical and food isolates of
      Listeria monocytogenes in Greece, a total of 61 L. monocytogenes non-duplicate
      isolates, recovered from clinical specimens (n=19) and food (n=42), were
      serotyped and genotyped using two different Random Amplification of Polymorphic
      DNA (RAPD) protocols and Multiple Locus Variable Number Tandem Repeat Analysis
      (MLVA). Serotype group 4b, 4d, 4e prevailed (39.4%), among both clinical and food
      isolates, followed by serotype group 1/2a, 3a (23.0%), which nevertheless was
      detected only among food isolates. The most discriminatory typing protocol was
      MLVA, which grouped four isolates into two pairs, while the remaining isolates
      produced unique fingerprints. Similar results were obtained when taking into
      account the combination of the two RAPD protocols (Simpson index 0.999); six
      isolates were grouped into three pairs, two of which were the pairs that were
      identified also by MLVA. Single use of each RAPD protocol resulted in inferior
      discrimination (Simpson index 0.978 and 0.997, respectively). In conclusion, the
      two molecular procedures, MLVA, and the combined RAPD protocols, produced similar
      results, showing that L. monocytogenes isolates from clinical and food specimens
      were highly heterogenous and that clustering was very uncommon.

PMID- 22880959
TI  - Robust surface nano-architecture by alkali-carboxylate ionic bonding.
AB  - Ionic bonding in supramolecular surface networks is a promising strategy to self
      assemble nanostructures from organic building blocks with atomic precision.
      However, sufficient thermal stability of such systems has not been achieved at
      metal surfaces, likely due to partial screening of the ionic interactions. We
      demonstrate excellent stability of a self-assembled ionic network on a metal
      surface at elevated temperatures. The structure is characterized directly by
      atomic resolution scanning tunneling microscopy (STM) experiments conducted at
      165  degrees C showing intact domains. This robust nanometer-scale structure is
      achieved by the on-surface reaction of a simple and inexpensive compound, sodium
      chloride, with a model system for carboxylate interactions, terephthalic acid
      (TPA). Rather than distinct layers of TPA and NaCl, angle resolved X-ray
      photoelectron spectroscopy experiments indicate a replacement reaction on the
      Cu(100) surface to form Na-carboxylate ionic bonds. Chemical shifts in core level
      electron states confirm a direct interaction and a +1 charge state of the Na.
      High-temperature STM imaging shows virtually no fluctuation of Na-TPA island
      boundaries, revealing a level of thermal stability that has not been previously
      achieved in noncovalent organic-based nanostructures at surfaces. Comparable
      strength of intermolecular ionic bonds and intramolecular covalent bonds has been
      achieved in this surface system. The formation of these highly ordered structures
      and their excellent thermal stability is dependent on the interplay of adsorbate
      substrate and ionic interactions and opens new possibilities for ionic self
      assemblies at surfaces with specific chemical function. Robust ionic surface
      structures have potential uses in technologies requiring high thermal stability
      and precise ordering through self-assembly.

PMID- 22880960
TI  - Size-selective biocatalysis of myoglobin immobilized into a mesoporous metal
      organic framework with hierarchical pore sizes.
AB  - The protein myoglobin has been successfully immobilized into a mesoporous metal
      organic framework with hierarchical pore sizes, which demonstrates interesting
      size-selective biocatalysis as well as superior catalytic activities toward small
      substrate oxidation compared to its mesoporous silica material counterpart.

PMID- 22880961
TI  - Pattern formation in prey-taxis systems.
AB  - In this paper, we consider spatial predator-prey models with diffusion and prey
      taxis. We investigate necessary conditions for pattern formation using a variety
      of non-linear functional responses, linear and non-linear predator death terms,
      linear and non-linear prey-taxis sensitivities, and logistic growth or growth
      with an Allee effect for the prey. We identify combinations of the above non
      linearities that lead to spatial pattern formation and we give numerical
      examples. It turns out that prey-taxis stabilizes the system and for large prey
      taxis sensitivity we do not observe pattern formation. We also study and find
      necessary conditions for global stability for a type I functional response,
      logistic growth for the prey, non-linear predator death terms, and non-linear
      prey-taxis sensitivity.

PMID- 22880962
TI  - A mathematical model for malaria involving differential susceptibility,
      exposedness and infectivity of human host.
AB  - The main purpose of this article is to formulate a deterministic mathematical
      model for the transmission of malaria that considers two host types in the human
      population. The first type is called "non-immune" comprising all humans who have
      never acquired immunity against malaria and the second type is called "semi
      immune". Non-immune are divided into susceptible, exposed and infectious and semi
      immune are divided into susceptible, exposed, infectious and immune. We obtain an
      explicit formula for the reproductive number, R(0) which is a function of the
      weight of the transmission semi-immune-mosquito-semi-immune, R(0a), and the
      weight of the transmission non-immune-mosquito-non-immune, R(0e). Then, we study
      the existence of endemic equilibria by using bifurcation analysis. We give a
      simple criterion when R(0) crosses one for forward and backward bifurcation. We
      explore the possibility of a control for malaria through a specific sub-group
      such as non-immune or semi-immune or mosquitoes.

PMID- 22880963
TI  - Kolmogorov-type competition model with finitely supported allocation profiles and
      its applications to plant competition for sunlight.
AB  - A Kolmogorov-type competition model featuring allocation profiles, gain
      functions, and cost parameters is examined. For plant species that compete for
      sunlight according to the canopy partitioning model [R.R. Vance and A.L. Nevai,
      Plant population growth and competition in a light gradient: a mathematical model
      of canopy partitioning, J. Theor. Biol. 245 (2007), pp. 210-219] the allocation
      profiles describe vertical leaf placement, the gain functions represent rates of
      leaf photosynthesis at different heights, and the cost parameters signify the
      energetic expense of maintaining tall stems necessary for gaining a competitive
      advantage in the light gradient. The allocation profiles studied here, being
      supported on three alternating intervals, determine "interior" and "exterior"
      species. When the allocation profile of the interior species is a delta function
      (a big leaf) then either competitive exclusion or coexistence at a single
      globally attracting equilibrium point occurs. However, if the allocation profile
      of the interior species is piecewise continuous or a weighted sum of delta
      functions (multiple big leaves) then multiple coexistence states may also occur.

PMID- 22880964
TI  - Modelling the lethargic crab disease.
AB  - The lethargic crab disease (LCD) is an emergent infirmity that has decimated
      native populations of the mangrove land crab (Ucides cordatus, Decapoda:
      Ocypodidae) along the Brazilian coast. Several potential etiological agents have
      been linked with LCD, but only in 2005 was it proved that it is caused by an
      ascomycete fungus. This is the first attempt to develop a mathematical model to
      describe the epidemiological dynamics of LCD. The model presents four possible
      scenarios, namely, the trivial equilibrium, the disease-free equilibrium, endemic
      equilibrium, and limit cycles arising from a Hopf bifurcation. The threshold
      values depend on the basic reproductive number of crabs and fungi, and on the
      infection rate. These scenarios depend on both the biological assumptions and the
      temporal evolution of the disease. Numerical simulations corroborate the
      analytical results and illustrate the different temporal dynamics of the crab and
      fungus populations.

PMID- 22880965
TI  - Association between competition and obligate mutualism in a chemostat.
AB  - In this paper, we consider a simple chemostat model involving two obligate
      mutualistic species feeding on a limiting substrate. Systems of differential
      equations are proposed as models of this association. A detailed qualitative
      analysis is carried out. We show the existence of a domain of coexistence, which
      is a set of initial conditions in which both species survive. We demonstrate,
      under certain supplementary assumptions, the uniqueness of the stable equilibrium
      point which corresponds to the coexistence of the two species.

PMID- 22880966
TI  - Ice-structuring mechanism for zirconium acetate.
AB  - The control of ice nucleation and growth is critical in many natural and
      engineering situations. However, very few compounds are able to interact directly
      with the surface of ice crystals. Ice-structuring proteins, found in certain
      fish, plants, and insects, bind to the surface of ice, thereby controlling their
      growth. We recently revealed the ice-structuring properties of zirconium acetate,
      which are similar to those of ice-structuring proteins. Because zirconium acetate
      is a salt and therefore different from proteins having ice-structuring
      properties, its ice-structuring mechanism remains unelucidated. Here we
      investigate this ice-structuring mechanism through the role of the concentration
      of zirconium acetate and the ice crystal growth velocity. We then explore other
      compounds presenting similar functional groups (acetate, hydroxyl, or carboxylic
      groups). On the basis of these results, we propose that zirconium acetate adopts
      a hydroxy-bridged polymer structure that can bind to the surface of the ice
      crystals through hydrogen bonding, thereby slowing down the ice crystal growth.

PMID- 22880967
TI  - Nonsuicidal self-injury in an ethnically diverse college sample.
AB  - Self-report data pertaining to Nonsuicidal Self-Injury (NSSI; e.g., cutting) were
      collected from 5,691 undergraduates at a Midwestern urban university. Consistent
      with the small literature on NSSI among college students, 12.8% of the sample
      indicated having engaged in NSSI at least once (3.4% in the past year). Women and
      younger students were at slightly higher risk. Important ethnic differences were
      found, as Caucasians and individuals self-identifying as Multiracial were at
      especially high risk for a history of NSSI, whereas Arab Americans and African
      Americans had particularly low rates. Further, links between NSSI and religion
      were found, such that participants with stronger self-reported religious
      convictions had the lowest rates of NSSI. Those who self-described as Atheist,
      Agnostic, or Nonbeliever were several times more likely to have engaged in NSSI
      (31.3%), while Muslims (7.4%) and Baptists (6.3%) had relatively low rates.
      Multivariate analyses revealed that ethnic differences in NSSI could not be
      accounted for by religious differences. Processes that may explain the
      associations between NSSI and ethnic affiliation and religion are discussed.

PMID- 22880968
TI  - Deliberate self-harm behavior among Italian young adults: correlations with
      clinical and nonclinical dimensions of personality.
AB  - This study aims to explore rates of deliberate self-harm (DSH) behaviors and
      their psychological and psychopathological correlates within a sample of
      nonclinical young adults (N = 365; 63% women; M age = 23 +/- 4.06). Participants
      completed the Deliberate Self-Harm Inventory and other self-report questionnaires
      assessing clinical (borderline personality, dissociative, and depersonalization
      traits) and nonclinical (body perception, behavioral inhibition and activation,
      cognitive emotional regulation, and the Big Five traits) dimensions of their
      personality. The rate of DSH in the present sample was 39%, comparable to that
      found in previous studies of young adults in other countries. Further, consistent
      with past research, DSH was found to be associated with clinical dimensions of
      personality pathology, including borderline personality and dissociative
      symptoms. Finally, results revealed an association between DSH and nonclinical
      dimensions of personality, including the behavioral activation dimension of fun
      seeking, more negative body perception and lower body protection, the use of more
      nonadaptive cognitive strategies for regulating emotions, higher levels of
      openness to experience, and lower levels of emotional stability. This pattern of
      results is consistent with those found for other impulsive behaviors and impulse
      control disorders.

PMID- 22880969
TI  - Asian Americans' family cohesion and suicide ideation: moderating and mediating
      effects.
AB  - The purpose of this study was to examine the relationship between family cohesion
      and suicide ideation in a national, adult community sample of Asian Americans
      (N=2072). The data for this study were drawn from the National Latino and Asian
      American Study, the first national epidemiological study of Asian Americans'
      mental health. The results indicate that family cohesion was negatively related
      to suicide ideation. In addition, English language proficiency moderated the
      relationship between family cohesion and suicide ideation. Family cohesion was
      related to lower odds of suicide ideation among low English proficiency Asian
      Americans. In contrast, family cohesion was not significantly related to suicide
      ideation among high English proficiency Asian Americans. Further, the findings
      are consistent with a model in which the relationship between family cohesion and
      suicide ideation was partially mediated by psychological distress. Practical
      implications for addressing suicide ideation among Asian Americans are discussed.

PMID- 22880970
TI  - Sacrifice for the sake of the family: expressions of familism by Latina teens in
      the context of suicide.
AB  - Familism is a core value promoted by many individuals of Hispanic or Latino
      descent that emphasizes the primacy of the family over the individual. This study
      illuminates some aspects of the relationship between familism and adolescent
      suicidal behavior. Qualitative data from 24 female Hispanic teens with and
      without a history of suicidal behaviors and their parents were analyzed to
      understand the ways in which familism is expressed in their lives. Both suicide
      attempters and nonattempters demonstrate familism by making material or emotional
      (or both) sacrifices for the sake of their families. However, for those
      attempters who expressed a clear intent to die, a third type of sacrifice
      emerged: Girls expressed a desire to kill themselves in order to make things
      better for their families, literally sacrificing themselves for the sake of
      family. Findings point to the complexity of familism in understanding the risks
      of suicide attempts among teen Latinas and to the value of mixed methods in
      studying deeply the cultural factors that influence problem behaviors.

PMID- 22880971
TI  - Child maltreatment and deliberate self-harm among college students: testing
      mediation and moderation models for impulsivity.
AB  - This study examined the relationship between child maltreatment, impulsivity, and
      deliberate self-harm in a sample of college students. Four subtypes of
      impulsivity (urgency, premeditation, perseverance, and sensation seeking) were
      examined. Results show that participants who report child maltreatment histories
      also report higher levels of negative affect and higher levels of impulsivity,
      specifically negative urgency. In addition, those who report histories of child
      maltreatment are more likely to endorse deliberate self-harm behaviors as an
      adult. Of the 4 subtypes of impulsivity, urgency was most strongly related to
      deliberate self-harm. Urgency, but not the other subtypes of impulsivity,
      mediated the relationship between child maltreatment and self-harm. The current
      study contributes to the understanding of the mechanisms behind deliberate self
      harm behavior by suggesting that individuals with histories of child maltreatment
      are more likely to engage in deliberate self-harm in an attempt to quickly reduce
      intense negative affect.

PMID- 22880972
TI  - Potential treatment mechanisms of counseling for children in Burundi: a series of
      n=1 studies.
AB  - Little is known about the impact and treatment processes of psychosocial
      counseling in low-income countries. This study aimed to generate hypotheses on
      key working mechanisms of counseling in Burundi. The authors carried out 11
      empirically grounded n=1 studies with children (11-14years) screened for
      depression and anxiety who received counseling. The authors used quantitative
      (symptom scales) and qualitative instruments (treatment content and perceptions).
      Weekly measurements were taken preintervention (4 time points), during the
      intervention period (8-10 time points), and postintervention (4 time points).
      Five treatment mechanisms continua appeared associated with outcome trajectories:
      client centeredness, therapeutic alliance, active problem solving, trauma-focused
      exposure, and family involvement. Higher levels appeared associated with better
      outcomes. Contrarily, cases that demonstrated no change were characterized by a
      heavy focus on counselors' norms, containment and self-control, unstructured
      retelling and explicit avoidance, advice-oriented problem solving, and
      noninclusion of family members, respectively. The authors found a distinct
      clustering of outcome trends per therapist. The findings suggest that integrative
      counseling, which combines universal therapist variables with active use of
      specific therapeutic techniques and a systemic perspective, may be an adequate
      strategy to treat mental health symptoms of children in Burundi.

PMID- 22880973
TI  - Does combining infant stimulation with emergency feeding improve psychosocial
      outcomes for displaced mothers and babies? A controlled evaluation from northern
      Uganda.
AB  - Combined psychosocial and nutrition interventions improve the development of
      infants. However, there is a paucity of studies examining the effectiveness of
      such interventions in humanitarian settings. This article examines the impact of
      combining a group-based psychosocial intervention with an existing emergency
      feeding program for internally displaced mothers in Northern Uganda. The
      intervention consisted of mother and baby group sessions and home visits for
      mothers attending 3 emergency feeding centers. Psychosocial outcomes were
      compared with a contrast group of mothers who received nutritional support alone.
      The outcomes investigated were infant stimulation and maternal mood. After
      controlling for the effects of interview site and baseline scores, mothers in the
      intervention group (n = 70) showed greater involvement with their babies, more
      availability of play materials, and less sadness and worry at follow-up in
      comparison to the contrast group (n = 77). The intervention was acceptable to the
      mothers and easily taught. A proportion of the mothers chose to continue the
      intervention spontaneously with other mothers in their neighbourhoods. Further
      research needs to be done to validate these preliminary findings and explore the
      longer term impact on child growth and intellectual development as well as
      maternal mood.

PMID- 22880974
TI  - The hope in her eyes: the role of children in Afghan women's resilience.
AB  - Although responsibility for the care, nurturance, and protection of children can
      sometimes be viewed as an additional stress in the lives of at-risk women, this
      article describes the ways in which children act as protective factors in support
      of Afghan women's resilience. The qualitative data presented come from 110
      interviews collected in Pakistan and Afghanistan between December 2001 and July
      2002 with Afghan women, children, and men associated with the Revolutionary
      Association of the Women of Afghanistan (RAWA). RAWA, founded in 1977, is an
      Afghan women's underground resistance organization that promotes resilience
      through humanitarian and political activities. An iterative coding framework was
      developed to identify and explore processes of resilience and domain specific
      stressors (risks) and resources (protective factors). This article discusses the
      role of children as protective factors for women and RAWA. Although this article
      explores a unique setting and context, the authors argue that attention to
      children's role as protective factors may provide an important, strengths-based
      approach and a useful mechanism to bolster women's resilience in an array of
      other contexts and conflicts.

PMID- 22880975
TI  - Bloodied but unbowed: resilience examined in a South asian community.
AB  - The construct of resilience was examined in a South Asian community impacted by
      natural and human-made disasters. Forty-three Sinhala, Tamil, and Muslim Sri
      Lankans (27 women; age range 21-62 years) participated in 6 focus groups,
      conducted in either Sinhala or Tamil, to elicit participants' own ideas about
      components of resilience. Schema analysis of transcripts revealed that although
      some elements of resilience were common across ethnocultural groups, others
      differed by ethnic group. The differences appeared to be as much a function of
      type of trauma exposure as of culture. Components of resilience included many
      that are recognized in the western construct of resilience as well as 2
      culturally unique components: strong will relating either to religious faith or
      to karma and psychosocial gratitude. These components could be examined in future
      measures of resilience with similar populations. Findings also revealed that some
      components of resilience can be taught; thus they can be the focus of
      interventions and public health policies.

PMID- 22880976
TI  - Perceived ethnic discrimination and social exclusion: newcomer immigrant children
      in Canada.
AB  - This article examines relationships between perceived ethnic discrimination,
      social exclusion, psychosocial functioning, and academic performance among
      newcomer immigrant children from the People's Republic of China, Hong Kong, and
      the Philippines using a subsample from the New Canadian Children and Youth Study
      of children aged 11-13 years (1,053) living in Montreal, Toronto, Vancouver, and
      the Prairies. Bivariate analysis showed that 25% of children reported being
      treated unfairly by peers and 14% by teachers because of who they are. Regression
      analyses revealed that perceived ethnic discrimination by peers and teachers was
      negatively related to children's sense of social competence in peer
      relationships. Children's self-esteem and sense of academic competence were
      negatively related to perceived discrimination by teachers. One in 5 children
      reported feeling like an outsider, with boys revealing higher levels of
      psychological isolation than girls. More than 1 in 10 were socially isolated and
      reported never participating in organized activities. This may reflect economic
      exclusion, as over one third of respondents belonged to families living below the
      Canadian Income Adequacy Measure. Psychological isolation, social isolation, and
      economic exclusion were significant predictors of children's sense of academic
      competence and actual academic grades. Variations exist across age, sex,
      ethnicity, family structure, parental education, region of settlement, and length
      of time since arrival in Canada.

PMID- 22880977
TI  - Understanding the ecology and development of children and families experiencing
      homelessness: implications for practice, supportive services, and policy.
AB  - The experience of homelessness can pervade multiple levels and facets of a child
      and family's world. In view of the historical risks in the lives of children who
      are experiencing homelessness (e.g., growing up under conditions of poverty,
      exposure to family violence), it is clear that interventions, services, and
      supports need to be equally comprehensive to have a positive influence on child
      functioning and development. Consequently, service systems, providers, and
      community supports need to address the circumstances of children and families
      experiencing homelessness and, more specifically, better attend to their
      ecologies and the diverse factors that can affect their well-being and adjustment
      trajectories. Such an approach is needed to better understand the range of
      factors and influences on the development and adaptation of these youngsters at
      home, at school, and with their peers as well as to guide the identification and
      implementation of adequate family-centered services and supports.

PMID- 22880978
TI  - Promoting positive parenting in the context of homelessness.
AB  - Recent national reports suggest that nearly 1,000,000 families with children
      experience homelessness and that this number is rising (National Center on Family
      Homelessness, 2009; U.S. Conference of Mayors, 2010; U.S. Department of Housing
      and Urban Development, 2011). Families experiencing homelessness are
      disproportionately more likely to have experienced economic, health, and social
      risk factors. These experiences can adversely influence the parent-child
      relationship. The purpose of this article is to (a) review the literature on the
      determinants and contextual issues of parenting in shelters; (b) describe
      specific programs that are focused on positive parenting in the context of
      homelessness; and (c) provide practice, research, and policy recommendations for
      supporting positive parenting among families living without homes.

PMID- 22880979
TI  - Impact of chronically street homeless tenants in congregate supportive housing.
AB  - New initiatives to house chronically street homeless (CSH) adults have led to
      increasing proportions of this population living in congregate supportive
      housing, but little is known about the impact of this shift on supportive housing
      programs. The present multisite, mixed-methods study examined service utilization
      and lease compliance among 52 chronically street homeless and 46 long-term
      shelter stayer (LTSS) adults during their first 12 months in congregate
      supportive housing. Quantitative analysis of administrative data revealed that
      CSH tenants used significantly more service resources than LTSS tenants,
      including more advocacy, escorting, and psychiatric treatment and more assistance
      with financial, housing, and mental and physical health issues. The 2 groups did
      not differ significantly on measures of lease compliance. Qualitative focus
      groups with CSH tenants, service provider staff, and property management staff
      all indicated that existing supportive housing services are suitable for this
      population, although some adjustments, additional resources, or both, may be
      indicated.

PMID- 22880980
TI  - Life course adversity in the lives of formerly homeless persons with serious
      mental illness: context and meaning.
AB  - This qualitative study assessed the frequency and subjective meaning of adverse
      experiences using case study analyses of interviews with 38 formerly homeless
      adults with co-occurring serious mental illness (SMI) and substance abuse
      histories. Adverse life events were inventoried using an adaptation of Lloyd and
      Turner's (2008) 41-item checklist. Participants averaged 8.8 adverse events, with
      approximately one-third having experienced incarceration (37%), suicidality
      (32%), abandonment by one or both parents (30%), and death of their mother (34%).
      Cross-case analyses yielded 3 themes: social losses because of death and
      estrangement; the significance of chronic stressors as well as acute events; and
      the cumulative lifetime nature of adversity. Findings suggest that life course
      experiences of trauma and loss have a cumulative influence in the lives of this
      population in addition and in relation to SMI, substance abuse, and homelessness.
      In this context, the mental health recovery movement should address prior adverse
      experiences beyond comorbid diagnoses in this population.

PMID- 22880981
TI  - Talking about immigration: community voices on service, research, and policy
      needs.

PMID- 22880982
TI  - Toward universal higher education, maybe.

PMID- 22880983
TI  - Respect: on witness and justice.

PMID- 22880984
TI  - A comparative study of hair removal at an NHS hospital: Luminette intense pulsed
      light versus electrolysis.
AB  - Twenty-five women, referred for hair removal by electrolysis, were enrolled in a
      split face study to treat facial hirsutism. Each patient was treated on six
      occasions: one-half of the face with electrolysis and the other side with an
      intense pulsed light source. Patients were evaluated with respect to reduction in
      hair counts, side effects and discomfort during treatment. Re-growth was assessed
      at 3, 6 and 9 months following treatment. All patients, except one with very
      sparse, fair hair growth, preferred treatment with the Intense Pulsed Light and
      rated their average hair reduction with this method as 77% after five treatments.
      The overall patient satisfaction rates as determined by visual analogue scales
      were 8.3 out of 10 for IPL and 5.4 out of 10 for electrolysis. 

PMID- 22881021
TI  - Vacuum extraction: development and test of a procedure-specific rating scale.
AB  - OBJECTIVES: To develop and validate an Objective Structured Assessment of
      Technical Skills (OSATS) scale for vacuum extraction. DESIGN: Two-part study
      design: Primarily, development of a procedure-specific checklist for vacuum
      extraction. Hereafter, validation of the developed OSATS scale for vacuum
      extraction in a prospective observational study. SETTING: Rigshospitalet,
      University Hospital of Copenhagen. POPULATION: For development, an obstetric
      expert from each labor ward in Denmark (28 departments) was invited to
      participate. For validation, nine first-year residents and 10 chief physicians
      with daily work in the obstetric field were tested. METHODS: The Delphi method
      was used for development of the scale. In a simulated vacuum extraction scenario,
      first-year residents and obstetric chief physicians were rated using the
      developed OSATS scale for vacuum extraction to test construct validity of the
      scale. MAIN OUTCOME MEASURES: Consensus for the content of the scale. To test the
      scale of Cronbach's alpha, interclass correlation and differential item function
      was calculated in the prospective study. RESULTS: 89% completed the first and 61%
      completed the second Delphi round. Hereafter, consensus was obtained. There was a
      significant difference between residents' and experts' performance for total
      score and for the score of the separate parts of the scale. Cronbach's alpha for
      total score and for the separate parts of the scale was 0.91-0.95 and interclass
      correlation 0.84-0.9. CONCLUSIONS: The OSATS scale for vacuum extraction is a
      reliable test for differentiating between competence levels in a simulated
      setting.

PMID- 22881022
TI  - Stochastic models for competing species with a shared pathogen.
AB  - The presence of a pathogen among multiple competing species has important
      ecological implications. For example, a pathogen may change the competitive
      outcome, resulting in replacement of a native species by a non-native species.
      Alternately, if a pathogen becomes established, there may be a drastic reduction
      in species numbers. Stochastic variability in the birth, death and pathogen
      transmission processes plays an important role in determining the success of
      species or pathogen invasion. We investigate these phenomena while studying the
      dynamics of deterministic and stochastic models for n competing species with a
      shared pathogen. The deterministic model is a system of ordinary differential
      equations for n competing species in which a single shared pathogen is
      transmitted among the n species. There is no immunity from infection, individuals
      either die or recover and become immediately susceptible, an SIS disease model.
      Analytical results about pathogen persistence or extinction are summarized for
      the deterministic model for two and three species and new results about stability
      of the infection-free state and invasion by one species of a system of n-1
      species are obtained. New stochastic models are derived in the form of continuous
      time Markov chains and stochastic differential equations. Branching process
      theory is applied to the continuous-time Markov chain model to estimate
      probabilities for pathogen extinction or species invasion. Finally, numerical
      simulations are conducted to explore the effect of disease on two-species
      competition, to illustrate some of the analytical results and to highlight some
      of the differences in the stochastic and deterministic models.

PMID- 22881023
TI  - A comparison of computational efficiencies of stochastic algorithms in terms of
      two infection models.
AB  - In this paper, we investigate three particular algorithms: a stochastic
      simulation algorithm (SSA), and explicit and implicit tau-leaping algorithms. To
      compare these methods, we used them to analyze two infection models: a Vancomycin
      resistant enterococcus (VRE) infection model at the population level, and a Human
      Immunodeficiency Virus (HIV) within host infection model. While the first has a
      low species count and few transitions, the second is more complex with a
      comparable number of species involved. The relative efficiency of each algorithm
      is determined based on computational time and degree of precision required. The
      numerical results suggest that all three algorithms have the similar
      computational efficiency for the simpler VRE model, and the SSA is the best
      choice due to its simplicity and accuracy. In addition, we have found that with
      the larger and more complex HIV model, implementation and modification of tau
      Leaping methods are preferred.

PMID- 22881024
TI  - Fast two dimensional to three dimensional registration of fluoroscopy and CT
      scans using Octrees on segmentation maps.
AB  - We introduce a computationally efficient approach to the generation of Digital
      Reconstructed Radiographs (DRRs) needed to perform three dimensional to two
      dimensional medical image registration and apply this algorithm to virtual
      surgery. The DRR generation process is the bottleneck of any three dimensional to
      two dimensional registration system, since its computational complexity scales
      with the number of voxels in the Computed Tomography Data, which can be of the
      order of tens to hundreds of millions. Our approach originates from the
      segmentation of the volumetric data into multiple regions, which allows a compact
      representation via Octree Data Structures. This, in turn, yields efficient
      storage and access of the attenuation indexes of the volumetric cells, required
      in the projection procedure that generates the DRR. A functional based on Mutual
      Information is then maximized to obtain the alignment of the DRR with the two
      dimensional X-ray fluoroscopy scans acquired during the operation. Promising
      experimental results on real data are presented.

PMID- 22881025
TI  - Impact of vaccine arrival on the optimal control of a newly emerging infectious
      disease: A theoretical study.
AB  - When a newly emerging human infectious disease spreads through a host population,
      it may be that public health authorities must begin facing the outbreaks and
      planning an intervention campaign when not all intervention tools are readily
      available. In such cases, the problem of finding optimal intervention strategies
      to minimize both the disease burden and the intervention costs may be addressed
      by considering multiple intervention regimes. In this paper, we consider the
      scenario in which authorities may rely initially only on non-pharmaceutical
      interventions at the beginning of the campaign, knowing that a vaccine will later
      be available, at an exogenous and known switching time. We use a two-stage
      optimal control problem over a finite time horizon to analyze the optimal
      intervention strategies during the whole campaign, and to assess the effects of
      the new intervention tool on the preceding stage of the campaign. We obtain the
      optimality systems of two connected optimal control problems, and show the
      solution profiles through numerical simulations.

PMID- 22881026
TI  - Parameter estimation and uncertainty quantification for an epidemic model.
AB  - We examine estimation of the parameters of Susceptible-Infective-Recovered (SIR)
      models in the context of least squares. We review the use of asymptotic
      statistical theory and sensitivity analysis to obtain measures of uncertainty for
      estimates of the model parameters and the basic reproductive number (R0)---an
      epidemiologically significant parameter grouping. We find that estimates of
      different parameters, such as the transmission parameter and recovery rate, are
      correlated, with the magnitude and sign of this correlation depending on the
      value of R0. Situations are highlighted in which this correlation allows R0 to be
      estimated with greater ease than its constituent parameters. Implications of
      correlation for parameter identifiability are discussed. Uncertainty estimates
      and sensitivity analysis are used to investigate how the frequency at which data
      is sampled affects the estimation process and how the accuracy and uncertainty of
      estimates improves as data is collected over the course of an outbreak. We assess
      the informativeness of individual data points in a given time series to determine
      when more frequent sampling (if possible) would prove to be most beneficial to
      the estimation process. This technique can be used to design data sampling
      schemes in more general contexts.

PMID- 22881027
TI  - Multiple endemic states in age-structured SIR epidemic models.
AB  - SIR age-structured models are very often used as a basic model of epidemic
      spread. Yet, their behaviour, under generic assumptions on contact rates between
      different age classes, is not completely known, and, in the most detailed
      analysis so far, Inaba (1990) was able to prove uniqueness of the endemic
      equilibrium only under a rather restrictive condition. Here, we show an example
      in the form of a 3x3 contact matrix in which multiple non-trivial steady states
      exist. This instance of non-uniqueness of positive equilibria differs from most
      existing ones for epidemic models, since it arises not from a backward
      transcritical bifurcation at the disease free equilibrium, but through two saddle
      node bifurcations of the positive equilibrium. The dynamical behaviour of the
      model is analysed numerically around the range where multiple endemic equilibria
      exist; many other features are shown to occur, from coexistence of multiple
      attractive periodic solutions, some with extremely long period, to quasi-periodic
      and chaotic attractors. It is also shown that, if the contact rates are in the
      form of a 2x2 WAIFW matrix, uniqueness of non-trivial steady states always holds,
      so that 3 is the minimum dimension of the contact matrix to allow for multiple
      endemic equilibria.

PMID- 22881028
TI  - Modeling the effects of introducing a new antibiotic in a hospital setting: A
      case study.
AB  - The increase in antibiotic resistance continues to pose a public health risk as
      very few new antibiotics are being produced, and bacteria resistant to currently
      prescribed antibiotics is growing. Within a typical hospital setting, one may
      find patients colonized with bacteria resistant to a single antibiotic, or, of a
      more emergent threat, patients may be colonized with bacteria resistant to
      multiple antibiotics. Precautions have been implemented to try to prevent the
      growth and spread of antimicrobial resistance such as a reduction in the
      distribution of antibiotics and increased hand washing and barrier preventions;
      however, the rise of this resistance is still evident. As a result, there is a
      new movement to try to re-examine the need for the development of new
      antibiotics. In this paper, we use mathematical models to study the possible
      benefits of implementing a new antibiotic in this setting; through these models,
      we examine the use of a new antibiotic that is distributed in various ways and
      how this could reduce total resistance in the hospital. We compare several
      different models in which patients colonized with both single and dual-resistant
      bacteria are present, including a model with no additional treatment protocols
      for the population colonized with dual-resistant bacteria as well as models
      including isolation and/or treatment with a new antibiotic. We examine the
      benefits and limitations of each scenario in the simulations presented.

PMID- 22881029
TI  - The mathematical analysis of a syntrophic relationship between two microbial
      species in a chemostat.
AB  - A mathematical model involving a syntrophic relationship between two populations
      of bacteria in a continuous culture is proposed. A detailed qualitative analysis
      is carried out as well as the analysis of the local and global stability of the
      equilibria. We demonstrate, under general assumptions of monotonicity which are
      relevant from an applied point of view, the asymptotic stability of the positive
      equilibrium point which corresponds to the coexistence of the two bacteria. A
      syntrophic relationship in the anaerobic digestion process is proposed as a real
      candidate for this model.

PMID- 22881030
TI  - A mathematical model for within-host Toxoplasma gondii invasion dynamics.
AB  - Toxoplasma gondii (T. gondii) is a protozoan parasite that infects a wide range
      of intermediate hosts, including all mammals and birds. Up to 20% of the human
      population in the US and 30% in the world are chronically infected. This paper
      presents a mathematical model to describe intra-host dynamics of T. gondii
      infection. The model considers the invasion process, egress kinetics,
      interconversion between fast-replicating tachyzoite stage and slowly replicating
      bradyzoite stage, as well as the host's immune response. Analytical and numerical
      studies of the model can help to understand the influences of various parameters
      to the transient and steady-state dynamics of the disease infection.

PMID- 22881031
TI  - A minimal mathematical model for the initial molecular interactions of death
      receptor signalling.
AB  - Tumor necrosis factor (TNF) is the name giving member of a large cytokine family
      mirrored by a respective cell membrane receptor super family. TNF itself is a
      strong proinflammatory regulator of the innate immune system, but has been also
      recognized as a major factor in progression of autoimmune diseases. A subgroup of
      the TNF ligand family, including TNF, signals via so-called death receptors,
      capable to induce a major form of programmed cell death, called apoptosis.
      Typical for most members of the whole family, death ligands form homotrimeric
      proteins, capable to bind up to three of their respective receptor molecules. But
      also unligated receptors occur on the cell surface as homomultimers due to a
      homophilic interaction domain. Based on these two interaction motivs
      (ligand/receptor and receptor/receptor) formation of large ligand/receptor
      clusters can be postulated which have been also observed experimentally. We use
      here a mass action kinetics approach to establish an ordinary differential
      equations model describing the dynamics of primary ligand/receptor complex
      formation as a basis for further clustering on the cell membrane. Based on
      available experimental data we develop our model in a way that not only
      ligand/receptor, but also homophilic receptor interaction is encompassed. The
      model allows formation of two distict primary ligand/receptor complexes in a
      ligand concentration dependent manner. At extremely high ligand concentrations
      the system is dominated by ligated receptor homodimers.

PMID- 22881032
TI  - Global properties of a delayed SIR epidemic model with multiple parallel
      infectious stages.
AB  - In this paper, we study the global properties of an SIR epidemic model with
      distributed delays, where there are several parallel infective stages, and some
      of the infected cells are detected and treated, which others remain undetected
      and untreated. The model is analyzed by determining a basic reproduction number
      R0, and by using Lyapunov functionals, we prove that the infection-free
      equilibrium E0 of system (3) is globally asymptotically attractive when R0 <= 1,
      and that the unique infected equilibrium E* of system (3) exists and it is
      globally asymptotically attractive when R0 > 1.

PMID- 22881034
TI  - Degradation study of carnosic acid, carnosol, rosmarinic acid, and rosemary
      extract (Rosmarinus officinalis L.) assessed using HPLC.
AB  - Rosemary, whose major caffeoyl-derived and diterpenoid ingredients are rosmarinic
      acid, carnosol, and carnosic acid, is an important source of natural antioxidants
      and is being recognized increasingly as a useful preservative, protectant, and
      even as a potential medicinal agent. Understanding the stability of these
      components and their mode of interaction in mixtures is important if they are to
      be utilized to greatest effect. A study of the degradation of rosmarinic acid,
      carnosol, carnosic acid, and a mixture of the three was conducted in ethanolic
      solutions at different temperatures and light exposure. As expected, degradation
      increased with temperature. Some unique degradation products were formed with
      exposure to light. Several degradation products were reported for the first time.
      The degradation products were identified by HPLC/MS/MS, UV, and NMR. The
      degradation of rosemary extract in fish oil also was investigated, and much
      slower rates of degradation were observed for carnosic acid. In the mixture of
      the three antioxidants, carnosic acid serves to maintain levels of carnosol,
      though it does so at least in part at the cost of its own degradation.

PMID- 22881035
TI  - Anomalous behaviors of visible luminescence from graphene quantum dots: interplay
      between size and shape.
AB  - For the application of graphene quantum dots (GQDs) to optoelectronic
      nanodevices, it is of critical importance to understand the mechanisms which
      result in novel phenomena of their light absorption/emission. Here, we present
      size-dependent shape/edge-state variations of GQDs and visible photoluminescence
      (PL) showing anomalous size dependences. With varying the average size (d(a)) of
      GQDs from 5 to 35 nm, the peak energy of the absorption spectra monotonically
      decreases, while that of the visible PL spectra unusually shows nonmonotonic
      behaviors having a minimum at d(a) = ~17 nm. The PL behaviors can be attributed
      to the novel feature of GQDs, that is, the circular-to-polygonal-shape and
      corresponding edge-state variations of GQDs at d(a) = ~17 nm as the GQD size
      increases, as demonstrated by high-resolution transmission electron microscopy.

PMID- 22881036
TI  - The identification of chlorinated acetones in analyses of aged triacetone
      triperoxide (TATP).
AB  - The organic peroxide explosive triacetone triperoxide (TATP) is regularly
      encountered by law enforcement agents in various stages of its production,
      storage, or usage. In a previous study, it has been demonstrated that isolated,
      rigorously purified, TATP may degrade to form a series of chlorinated acetones
      when directly treated with excess concentrated hydrochloric acid. The current
      study extends this work to examine whether this phenomenon may be measured during
      the more feasible scenario of aging of rudimentarily purified TATP contaminated
      with trace reaction mixture. It was demonstrated that solid-phase microextraction
      gas chromatography/mass spectrometry analyses of aged TATP that was synthesized
      utilizing hydrochloric acid catalyst may identify the presence of the degradation
      products chloroacetone and 1,1-dichloroacetone. Upon aging of TATP synthesized
      utilizing either sulfuric or nitric acid catalyst, no acid specific degradation
      products could be identified. These findings may be exploited by forensic
      chemists in the analyses of TATP samples.

PMID- 22881037
TI  - Anatomical feasibility of performing intercostal and ilioinguinal nerve to pelvic
      nerve transfer: a possible technique to restore lower urinary tract innervation.
AB  - OBJECT: Nerve transfers are effective for restoring control to paralyzed somatic
      muscle groups and, recently, even to denervated detrusor muscle in a canine
      model. A pilot project was performed in cadavers to examine the feasibility of
      transferring somatic nerves to vesical branches of the pelvic nerve as a method
      for potentially restoring innervation to control the detrusor muscle in humans.
      METHODS: Eleven cadavers were dissected bilaterally to expose intercostal,
      ilioinguinal, and iliohypogastric nerves, along with vesical branches of the
      pelvic nerve. Ease of access and ability to transfer the former 3 nerves to the
      pelvic vesical nerves were assessed, as were nerve cross-sectional areas.
      RESULTS: The pelvic vesical nerves were accessed at the base of the bladder,
      inferior to the ureter and accompanied by inferior vesical vessels. The T-11 and
      T-12 intercostal nerves were too short for transfer to the pelvic vesical nerves
      without grafting. Ilioinguinal and iliohypogastric nerves (L-1 origin) were
      identified retroperitoneally and, with full dissection, were easily transferred
      to the pelvic vesical nerves intraabdominally. The mean cross-sectional area of
      the dominant pelvic vesical branch was 2.60 +/- 0.169 mm(2); ilioinguinal and
      iliohypogastric branches at the suggested transection site were 2.38 +/- 0.32
      mm(2) (the means are expressed +/- SEM). CONCLUSIONS: Use of the ilioinguinal or
      iliohypogastric nerves for heterotopic transfer to pelvic vesical nerves is
      surgically feasible, based on anatomical location and cross-sectional areas.

PMID- 22881038
TI  - Comparison of mini-open anterior corpectomy and posterior total en bloc
      spondylectomy for solitary metastases of the thoracolumbar spine.
AB  - OBJECT: The object of this study was to compare the mini-open anterior corpectomy
      procedure with posterior total en bloc spondylectomy (TES) in treating patients
      with solitary metastases of the thoracolumbar spine. METHODS: From 2004 to 2010,
      41 patients with solitary metastases of the thoracolumbar spine were treated in
      our hospital using either a mini-open anterior corpectomy or posterior TES.
      Intraoperative and diagnostic data, including perioperative complications, were
      collected using retrospective chart review. The surgical outcomes were assessed
      according to survival status, neurological function, local recurrence, and pain
      before and after surgery. RESULTS: Seventeen patients underwent posterior TES and
      24 underwent mini-open anterior corpectomy. Mean blood loss (TES, 1721 +/- 293
      ml; mini-open corpectomy, 1058 +/- 263 ml; p < 0.05), and mean operative time
      (TES, 403 +/- 55 minutes; mini-open corpectomy, 175 +/- 38 minutes; p < 0.05)
      were recorded and calculated. Neurological improvement by at least 1 American
      Spinal Injury Association Impairment Scale grade was noted in 35 (97.2%) of the
      36 cases with preoperative deficits. After the operation, 68.4% of nonambulatory
      patients became ambulatory again, including 84.6% after mini-open corpectomy and
      33.3% after posterior TES (p > 0.05). The visual analog scale scores of the
      patients were significantly reduced after both procedures, with no difference
      between the procedures (p > 0.05). The local tumor recurrence rate of the TES
      group was significantly lower than that of the mini-open corpectomy group (p <
      0.05), while the postoperative survival rates within 2 years after surgery were
      similar. The complication rate in the mini-open corpectomy group (29.2%) was
      higher than that in the TES group (11.8%), but this difference was not
      statistically significant (p = 0.185). There was no hardware failure and no loss
      of the sagittal Cobb angle in either group. Slight subsidence (< 3 mm) of the
      mesh cage was observed with a successful fusion in 3 (17.6%) of 17 patients in
      the TES group. No subsidence of polymethylmethacrylate block/autograft was
      recorded in the mini-open group. CONCLUSIONS: Mini-open anterior corpectomy can
      be accomplished with less blood loss, fewer fixation instrumentations, and
      shorter surgical time than that required for TES, but patients who undergo a mini
      open corpectomy might have a greater tendency to experience local recurrence. A
      mini-open anterior corpectomy has a relatively mild learning curve and involves
      fewer technical difficulties. With smaller incisions, mini-open anterior
      corpectomy is an option in treating solitary metastases of the thoracolumbar
      spine.

PMID- 22881039
TI  - A new criterion for the alarm point for compound muscle action potentials.
AB  - OBJECT: The purpose of this study was to review the present criteria for the
      compound muscle action potential (CMAP) alert and for safe spinal surgery.
      METHODS: The authors conducted a retrospective study of 295 patients in whom
      spinal cord monitoring had been performed during spinal surgery. The waveforms
      observed during spinal surgery were divided into the following 4 grades: Grade 0,
      normal; Grade 1, amplitude decrease of 50% or more and latency delay of 10% or
      more; Grade 2, multiphase pattern; and Grade 3, loss of amplitude. Waveform
      grading, its relationship with postoperative motor deficit, and CMAP sensitivity
      and specificity were analyzed. Whenever any wave abnormality occurred, the
      surgeon was notified and the surgical procedures were temporarily suspended. If
      no improvements were seen, the surgery was terminated. RESULTS: Compound muscle
      action potential wave changes occurred in 38.6% of cases. With Grade 1 or 2
      changes, no paresis was detected. Postoperative motor deficits were seen in 8
      patients, all with Grade 3 waveform changes. Among the 287 patients without
      postoperative motor deficits, CMAP changes were not seen in 181, with a
      specificity of 63%. The false-positive rate was 37% (106 of 287). However, when a
      Grade 2 change was set as the alarm point, sensitivity was 100% and specificity
      was 79.4%. The false-positive rate was 20% (59 of 295). CONCLUSIONS: Neither the
      Grade 1 nor the Grade 2 groups included patients who demonstrated a motor
      deficit. All pareses occurred in cases showing a Grade 3 change. Therefore, the
      authors propose a Grade 2 change (multiphasic waveform) as a new alarm point.
      With the application of this criterion, the false-positive rate can be reduced to
      20%.

PMID- 22881040
TI  - Endovascular obliteration of a ruptured posterior spinal artery pseudoaneurysm.
AB  - Aneurysms of the posterior spinal artery (PSA) are rare lesions. Isolated PSA
      aneurysms, not in the setting of a high-flow environment, are even more rare. In
      the few reported cases, these lesions have been predominantly resected or
      observed. The authors report an isolated pseudoaneurysm of the PSA at the T-11
      level presenting with subarachnoid hemorrhage. The patient underwent successful
      endovascular obliteration. To the authors' knowledge, this is the first report of
      an endovascular repair of an isolated PSA aneurysm.

PMID- 22881041
TI  - Spine metastasis.

PMID- 22881042
TI  - Light-triggered reversible supramolecular transformations of multi
      bisthienylethene hexagons.
AB  - It is very challenging to realize well-controlled structural transformations in
      artificial supramolecules. Herein we report the construction of a novel family of
      multi-bisthienylethene hexagons with precise control of the shape and size as
      well as the specific number of photochromic units via coordination-driven self
      assembly. These newly developed multi-bisthienylethene hexagons are highly
      sensitive and responsive to photostimuli, especially allowing for quantitative
      reversible supramolecular transformations triggered by light irradiation.

PMID- 22881043
TI  - Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for heavily
      pretreated relapsed or refractory multiple myeloma.
AB  - The combination of lenalidomide, bortezomib and dexamethasone (RVD) has shown
      excellent efficacy in patients with relapsed or refractory multiple myeloma
      (RRMM). The aim of our study was to assess the efficacy and toxicity profile of
      RVD for patients with advanced RRMM. We retrospectively reviewed the records of
      all patients with RRMM treated with RVD between March 2009 and December 2011.
      Thirty patients received >= 1 full cycle of RVD. Primary endpoints were overall
      response rate (ORR), progression-free survival (PFS) and overall survival (OS).
      After a median of 5 cycles (1-16), a very good partial response (VGPR) was seen
      in 10%, partial response (PR) in 36.7% and stable disease (SD) in 13.3% (ORR of
      46.7%). Disease progression occurred in 21 patients at a median of 3 months
      (range 1.41-4.59). Eight patients (26%) experienced grade 3/4 adverse events,
      including anemia, neutropenia, muscle weakness and pneumonia. No patient
      experienced worsening peripheral neuropathy. Although RVD has been previously
      shown to be effective in RRMM, the ORR and PFS we observed were affected by very
      advanced disease status and heavy prior exposure to novel agents. Nevertheless,
      six of these patients with RRMM experienced a benefit of >= 6 months, suggesting
      synergism of this immunomodulatory derivative/proteasome inhibitor combination
      and/or re-establishment of drug sensitivity by an emergent myeloma clone.

PMID- 22881044
TI  - Towards a better understanding of the legibility bias in performance assessments:
      the case of gender-based inferences.
AB  - BACKGROUND: Handwriting legibility systematically biases evaluations in that
      highly legible handwriting results in more positive evaluations than less legible
      handwriting. Because performance assessments in educational contexts are not only
      based on computerized or multiple choice tests but often include the evaluation
      of handwritten work samples, understanding the causes of this bias is critical.
      AIMS: This research was designed to replicate and extend the legibility bias in
      two tightly controlled experiments and to explore whether gender-based inferences
      contribute to its occurrence. SAMPLE(S): A total of 132 students from a German
      university participated in one pre-test and two independent experiments. METHOD:
      Participants were asked to read and evaluate several handwritten essays varying
      in content quality. Each essay was presented to some participants in highly
      legible handwriting and to other participants in less legible handwriting. In
      addition, the assignment of legibility to participant group was reversed from
      essay to essay, resulting in a mixed-factor design. RESULTS: The legibility bias
      was replicated in both experiments. Results suggest that gender-based inferences
      do not account for its occurrence. Rather it appears that fluency from legibility
      exerts a biasing impact on evaluations of content and author abilities.
      CONCLUSIONS: The legibility bias was shown to be genuine and strong. By refuting
      a series of alternative explanations, this research contributes to a better
      understanding of what underlies the legibility bias. The present research may
      inform those who grade on what to focus and thus help to better allocate
      cognitive resources when trying to reduce this important source of error.

PMID- 22881045
TI  - Small-group, computer-mediated argumentation in middle-school classrooms: the
      effects of gender and different types of online teacher guidance.
AB  - BACKGROUND: Research has shown the importance of careful teacher support during
      collaborative group work to promote productive discourse between students (Webb,
      2009). However, this research has traditionally focused on face-to-face
      communication. The role of online teacher guidance of small-group computer
      mediated discussions has received little attention, especially in secondary
      school classroom settings. Researchers of computer-supported collaborative
      learning (CSCL), on the other hand, have traditionally focused on software
      embedded features, such as scripts, to support a-synchronous peer dialogue, and
      less so on human guidance of synchronous group discussions. AIMS: The main aim of
      the present in vivo, experimental study is to examine whether online teacher
      guidance can improve the quality of small-group synchronous discussions, and
      whether different types of guidance (epistemic or interaction guidance) affect
      these discussions differently, when compared to an unguided condition. The second
      goal of this study is to explore potential differences between all-female and all
      male discussion groups. SAMPLE: Eighty-two 9th graders (three classrooms) and six
      teachers from a rural high school in Israel. RESULTS: Whereas epistemic guidance
      only improved aspects of the argumentative quality of the discussion, interaction
      guidance only improved aspects of collaboration. Discussions of all-girls groups
      scored higher on aspects of collaboration and argumentative quality, compared to
      all-boys groups. CONCLUSIONS: The findings show that teacher guidance of
      synchronous, online discussions in classrooms is realizable and reasonably
      reaches its intended goals. Training should be focused on acquiring various
      guidance strategies to augment their beneficial effects. Furthermore, future
      research should pay more attention to potential gender differences in peer-to
      peer argumentation.

PMID- 22881046
TI  - Instructional development for teachers in higher education: effects on students'
      perceptions of the teaching-learning environment.
AB  - BACKGROUND: Although instructional development for teachers has become an
      important topic in higher education, little is known about its actual impact. In
      particular, evidence regarding the impact of teachers' instructional development
      on students' perceptions of the teaching-learning environment is scarce. AIMS:
      The impact of an instructional development programme for beginning university
      teachers on students' perceptions of the teaching and learning environment was
      investigated. We also explored whether this impact is dependent on class size and
      student level (first years vs. non-first years). SAMPLE: Quantitative data were
      gathered from more than 1,000 students at pre- and post-tests, using a quasi
      experimental design. METHOD: A multi-level analysis was conducted in which five
      models were estimated. RESULTS: A basic model made clear that teachers did differ
      from each other with respect to the dependent variables concerned; however,
      differences in scale scores also resulted to a large extent from differences
      between students. A second model, in which the moderating impact by way of
      teacher characteristics, context, and student characteristics was not taken into
      account, reported no significant effect of training. A third model, examining the
      net impact of instructional development revealed some impact, which was,
      remarkably, negative. A first interaction model proved a differential impact of
      instructional development for teachers teaching first years and those teaching
      non-first years. A second one showed that the impact of training depended on the
      number of students one teaches. CONCLUSIONS: Instructional development for
      teachers in higher education does not easily result in effects on students'
      perceptions of the teaching and learning environment. Perspectives for further
      research into instructional development are discussed.

PMID- 22881047
TI  - How students' achievement goals shape their beliefs about effective teaching: a
      'build-a-professor' study.
AB  - BACKGROUND: Which instructor qualities do students consider most important? The
      answer likely depends on the student. This study attempted to trace beliefs about
      the most essential instructor qualities to students' academic achievement goals.
      AIMS: The present study tested the hypothesis that students pursuing mastery
      goals favour instructors who stimulate and challenge them intellectually, whereas
      those pursuing performance goals favour instructors who present material clearly
      and provide clear cues about how to succeed. SAMPLE: Participants were 157
      students at a 4-year public university. METHOD: Participants designed the ideal
      professor through a hypothetical combination of nine widely valued instructor
      qualities, such as enthusiasm, presentation clarity, and an interactive teaching
      style. The more they acquired of any one instructor quality, the less they could
      acquire of the others, thus compelling students to distinguish necessary
      qualities from desirable luxury qualities. RESULTS: Students' achievement goals
      corresponded to their views about the most essential instructor qualities.
      Mastery goals predicted greater demand for professors who intellectually
      challenge students and possess topic expertise, whereas performance goals
      predicted high demand for professors who present material clearly and provide
      cues about how to succeed in the course. CONCLUSIONS: The findings support
      emerging theorizing about how mastery and performance goals nudge students to
      pursue different learning agendas, with distinct consequences to their learning
      experience.

PMID- 22881048
TI  - Developing procedural flexibility: are novices prepared to learn from comparing
      procedures?
AB  - BACKGROUND: A key learning outcome in problem-solving domains is the development
      of procedural flexibility, where learners know multiple procedures and use them
      appropriately to solve a range of problems (e.g., Verschaffel, Luwel, Torbeyns, &
      Van Dooren, 2009). However, students often fail to become flexible problem
      solvers in mathematics. To support flexibility, teaching standards in many
      countries recommend that students be exposed to multiple procedures early in
      instruction and be encouraged to compare them. AIMS: We experimentally evaluated
      this recommended instructional practice for supporting procedural flexibility
      during a classroom lesson, relative to two alternative conditions. The
      alternatives reflected the common instructional practice of delayed exposure to
      multiple procedures, either with or without comparison of procedures. SAMPLE:
      Grade 8 students from two public schools (N= 198) were randomly assigned to
      condition. Students had not received prior instruction on multi-step equation
      solving, which was the topic of our lessons. METHOD: Students learned about multi
      step equation solving under one of three conditions in math class for about 3 hr.
      They also completed a pre-test, post-test, and 1-month-retention test on their
      procedural knowledge, procedural flexibility, and conceptual knowledge of
      equation solving. RESULTS: Novices who compared procedures immediately were more
      flexible problem solvers than those who did not, even on a 1-month retention
      test. Although condition had limited direct impact on conceptual and procedural
      knowledge, greater flexibility was associated with greater knowledge of both
      types. CONCLUSIONS: Comparing procedures can support flexibility in novices and
      early introduction to multiple procedures may be one important reason.

PMID- 22881049
TI  - General knowledge monitoring as a predictor of in-class exam performance.
AB  - BACKGROUND: Current theories of self-regulated learning predict a positive link
      between student monitoring accuracy and performance: students who more accurately
      monitor their knowledge of a particular set of materials are expected to more
      effectively regulate their subsequent study of those materials, which in turn
      should lead to higher test performance. AIMS: The present study further explored
      the link between monitoring accuracy and performance by investigating whether
      monitoring of one set of materials would predict performance on a different set
      of materials. SAMPLE: The participants were college students (N= 379) enrolled in
      an educational psychology course. Method. Students' monitoring accuracy was
      measured at the start of the semester; the monitoring task involved materials
      that were not related to class content (i.e., general knowledge vocabulary) and
      that were related to class content (i.e., terms from educational psychology).
      Target performance was students' scores on the final exam. RESULTS: Monitoring
      accuracy significantly predicted student performance on the final exam, even when
      the monitoring task and final test were based on materials from different content
      domains. Also, the class-related (vs. unrelated) materials in the monitoring task
      did not improve the predictive validity of monitoring accuracy, suggesting a
      limited role for domain specificity in the relationship between monitoring skill
      and performance. CONCLUSIONS: This study establishes a critical link between
      general monitoring accuracy and exam performance within a classroom setting.

PMID- 22881050
TI  - The nature of student teachers' regulation of learning in teacher education.
AB  - BACKGROUND: Self-regulated learning (SRL) has mainly been conceptualized to
      involve student learning within academic settings. In teacher education, where
      learning from theory and practice is combined, student teachers also need to
      regulate their learning. Hence, there is an urgent need to extend SRL theories to
      the domain of teacher learning and to obtain scientific knowledge on the nature
      of student teachers' SRL to enable support of these processes in teacher
      education. AIMS: This study was aimed at exploring the nature of student
      teachers' regulation of learning across various theoretical and practical
      contexts in teacher education. SAMPLE: Twenty-eight students from a post-graduate
      academic teacher education institute participated in this study. METHOD: For the
      measurement of student teachers' regulation activities, an open question log,
      called Learning Report, was developed. Content analysis and multiple
      correspondence analyses of 133 Learning Reports were used to identify qualitative
      differences in regulation activities and the underlying structure in the data.
      RESULTS: The analyses resulted in the identification and description of the
      variety and frequency of student teachers' regulation activities. The relations
      among the regulation activities were described by an underlying structure of two
      dimensions: passive versus active regulation of learning and prospective versus
      retrospective regulation of learning. Active regulation dominated in practice
      schools, passive regulation at the university. CONCLUSIONS: It is argued that for
      learning to teach, a different conceptualization of SRL is needed, focusing less
      on setting initial learning goals and more on retrospective aspects of SRL.
      Building blocks for such a conceptualization are offered.

PMID- 22881051
TI  - Are diagrams always helpful tools? developmental and individual differences in
      the effect of presentation format on student problem solving.
AB  - BACKGROUND: High school and college students demonstrate a verbal, or textual,
      advantage whereby beginning algebra problems in story format are easier to solve
      than matched equations (Koedinger & Nathan, 2004). Adding diagrams to the stories
      may further facilitate solution (Hembree, 1992; Koedinger & Terao, 2002).
      However, diagrams may not be universally beneficial (Ainsworth, 2006; Larkin &
      Simon, 1987). AIMS: To identify developmental and individual differences in the
      use of diagrams, story, and equation representations in problem solving. When do
      diagrams begin to aid problem-solving performance? Does the verbal advantage
      replicate for younger students? SAMPLE: Three hundred and seventy-three students
      (121 sixth, 117 seventh, 135 eighth grade) from an ethnically diverse middle
      school in the American Midwest participated in Experiment 1. In Experiment 2, 84
      sixth graders who had participated in Experiment 1 were followed up in seventh
      and eighth grades. METHOD: In both experiments, students solved algebra problems
      in three matched presentation formats (equation, story, story + diagram).
      RESULTS: The textual advantage was replicated for all groups. While diagrams
      enhance performance of older and higher ability students, younger and lower
      ability students do not benefit, and may even be hindered by a diagram's
      presence. CONCLUSIONS: The textual advantage is in place by sixth grade. Diagrams
      are not inherently helpful aids to student understanding and should be used
      cautiously in the middle school years, as students are developing competency for
      diagram comprehension during this time.

PMID- 22881052
TI  - Effects of a school reform on longitudinal stability of students' preferences
      with regard to education.
AB  - BACKGROUND: Students' perspective on education is of crucial importance for its
      effectivity, but students' opinions are seldom acknowledged by teachers and
      designers. Student participation in the educational design process could be a
      suitable tool to better take students' preferences into account. However, for
      effective participatory design, it is necessary to know whether students have
      stable preferences for the design of their education. Changeability of
      preferences would require a more continuing design process allowing continuous
      adaptations. AIMS: This longitudinal survey study aimed to determine the
      changeability over time of students' preferences for different aspects of a
      learning environment. Additionally, causes of possible changes in preferences are
      investigated. SAMPLE: The participants were 1,335 high school students of five
      schools for secondary education in the Netherlands, joining this study during a
      period of 2 years. METHOD: Data about students' preferences were collected at
      three moments, using the Inventory of Perceived Study Environment Extended.
      Learning-related student characteristics, such as processing strategies and
      motivational orientations, were measured with the Inventory of Learning Styles.
      Additionally, data on learning performances were collected. RESULTS: The results
      showed stability on preferences for almost all studied characteristics of the
      learning environment. Particularly remarkable was a drop in desirability for
      student autonomy. This was larger for students with a certificate-oriented
      motivation and smaller for self-regulated students. Additionally, poorly
      performing students had a larger decrease in preference for autonomy.
      CONCLUSIONS: The stability on most aspects supports that participatory design
      might result in fairly stable instructional designs, although caution is needed
      with respect to student autonomy.

PMID- 22881053
TI  - Detection and classification of related lipopolysaccharides via a small array of
      immobilized antimicrobial peptides.
AB  - A small array of antimicrobial peptides comprising three cysteine-terminated
      natural sequences covalently immobilized to pendant surface maleimide groups are
      used to bind and successfully discriminate five types of lipopolysaccharide (LPS)
      molecules. Using surface plasmon resonance, LPSs isolated from four strains of
      Escherichia coli and one strain of Pseudomonas aeruginosa yield distinct binding
      profiles to the three immobilized peptides. Linear discriminant analysis
      generated 100% training set and 80% validation set classification success for the
      40 samples evaluated. This work demonstrates the discriminatory binding
      capabilities of immobilized antimicrobial peptides toward LPS molecules and
      alludes to their use as probes in pathogen sensing devices potentially superior
      to the current state-of-the-art.

PMID- 22881054
TI  - Creating connections.

PMID- 22881055
TI  - Late HIV detection among adult males in Los Angeles County, 2000-2004.
AB  - We analyzed HIV surveillance data on white, black, and Latino males diagnosed
      with HIV between 2000 and 2004 in Los Angeles County (LAC) to identify
      associations between individual- and community-level factors and late HIV
      detection by race/ethnicity. We defined late HIV detection as an AIDS diagnosis
      within 6 months of HIV diagnosis. We conducted multilevel analysis to determine
      individual- and community-level risk factors associated with late HIV detection
      stratified by race/ethnicity. We mapped HIV-positive males with late HIV
      detection by race/ethnicity at the zip code level within LAC to determine high
      burden areas. Overall, 38% of all males met the definition of late HIV detection.
      By race/ethnicity, 44% of Latinos, 38% of blacks, and 30% of whites were detected
      late in their course of HIV infection. Latinos and whites had multiple individual
      level risk factors associated with late HIV detection. Among black males, only
      older age at HIV diagnosis was associated with late HIV detection. The only
      community-level risk factor associated with late HIV detection was among Latinos
      living in communities with less than 6% of men who have sex with men (proxy for
      stigma). Mapping the distribution of late HIV detection showed late detection
      areas generalized across LAC for Latino males in comparison with white and black
      males whose maps showed clustered areas of late HIV detection. Analysis and
      mapping of individual- and community-level risk factors associated with late HIV
      detection provides an important tool for targeting prevention resources to areas
      and populations with the highest burden of disease.

PMID- 22881056
TI  - The impact of obstetric unit closures on maternal and infant pregnancy outcomes.
AB  - OBJECTIVE: To define the association between large-scale obstetric unit closures
      and relative changes in maternal and neonatal outcomes. DATA SOURCES/STUDY
      SETTING: Birth and death certificates were linked to maternal and neonatal
      hospital discharge records for all births between January 1, 1995 and June 30,
      2005 in Philadelphia, which experienced the closure of 9 of 19 obstetric units
      between 1997 and 2005, and five surrounding counties and eight urban counties
      that did not experience a similar reduction in obstetric units. DESIGN: A before
      and-after study design with an untreated control group compared changes in
      perinatal outcomes in Philadelphia to five surrounding control counties and eight
      urban control counties after controlling for case mix differences and secular
      trends (N = 3,140,782). RESULTS: Relative to the preclosure years, the difference
      in neonatal mortality (odds ratio (OR) 1.49, 95 percent CI 1.12-2.00) and all
      perinatal mortality (OR 1.53, 95 percent CI 1.14-2.04) increased for Philadelphia
      residents compared with both control groups between 1997 and 1999. After 2000,
      there was no statistically significant change in any outcome in Philadelphia
      county compared with the preclosure epoch. CONCLUSIONS: Obstetric unit closures
      were initially associated with adverse changes in perinatal outcomes, but these
      outcomes ameliorated over time.

PMID- 22881057
TI  - Old and new HLA associations with ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that
      primarily involves the axial skeleton and the sacroiliac joint, but may also
      affect peripheral joints and entheses. AS susceptibility is clearly attributable
      to genetic factors and the link between human leukocyte antigen (HLA)-B27 and AS
      is the strongest association between an HLA class I molecule and a disease.
      However, there is evidence for the involvement of other, non-B27 factors within
      the major histocompatibility complex (MHC) in AS susceptibility. MHC class I is
      clearly the most significant genetic region for the disease, although most of the
      genetic association of this region is driven by HLA-B27. Moreover, several
      studies have investigated the MHC class II region and its association with AS.
      This review summarizes the current findings concerning the MHC genetics of the
      disease, focusing in particular on the associations of HLA with AS found in
      different ethnic populations throughout the world, and the possible mechanisms
      underlying them.

PMID- 22881058
TI  - Heterogeneity of HLA-DRB1*04 alleles and haplotypes in the Croatian population.
AB  - Analysis of allele distribution at the HLA-DRB1*04 gene, as one of the frequent
      ones among Croatians, and their HLA-A-B-DRB1 haplotypes in the Croatian
      population was performed in this study. Using LABType(r) SSO and PCR-SSP method,
      11 DRB1*04 subtypes were observed, of which DRB1*04:01 was the most frequent
      (28.0%) followed by DRB1*04:02 (26.3%), DRB1*04:03 (22.3%), and DRB1*04:04
      (14.2%). The significant haplotypes (with highest P value) for given DRB1*04
      allele were the following combinations: HLA-B*15:01-DRB1*04:01, HLA-B*38:01
      DRB1*04:02, HLA-B*35:03-DRB1*04:03, HLA-B*35:03-DRB1*04:08, HLA-B*14:01
      DRB1*04:04, and HLA-B*49-DRB1*04:05. Marked differences in the distribution of
      our most frequent haplotypes of HLA-B-DRB1*04 (HLA-B*38:01-DRB1*04:02 and HLA
      B*15:01-DRB1*04:01) were found in comparison to other European populations
      investigated so far. Additionally, comparison of HLA-A-B-DRB1*04 haplotypes
      showed that although there are similarities in the haplotype structure between
      our and other populations, there are also noteworthy differences. In summary, the
      identification of conserved and unusual DRB1*04 haplotypes in the present study
      of Croats should have important clinical implications for donor-recipient
      matching in the hematopoietic stem cell transplantation program, help in the
      understanding of HLA polymorphisms in different European populations, and also
      prove to be very useful in the determination of possible susceptibility genes
      involved in HLA-DRB1*04-associated diseases.

PMID- 22881059
TI  - Nomenclature for factors of the HLA system, update April  2012.

PMID- 22881060
TI  - Nomenclature for factors of the HLA system, update May 2012.

PMID- 22881061
TI  - Nomenclature for factors of the HLA system, update June 2012.

PMID- 22881062
TI  - MRI in the diagnosis and surgical management of abnormal placentation.
AB  - OBJECTIVE: To determine the usefulness of placental magnetic resonance imaging
      (MRI) in the diagnosis and surgical management of abnormal placentation. DESIGN:
      Retrospective follow-up. SETTING: Buenos Aires, Argentina. POPULATION: 547
      pregnant women. METHODS: In all cases, a direct and reliable description of
      abnormal placentation features was obtained by the operating surgeon. Placental
      MRI was analyzed according to: (1) primary description, (2) invasion topography,
      (3) modification required to the surgical tactics or techniques and (4) by
      positive and negative predictive values. MAIN OUTCOME MEASURES: Ultrasound and
      MRI findings were compared with surgical results, which were considered a final
      diagnosis in relation to primary diagnostic indications. RESULTS: Placental MRI
      was obtained because of diagnostic doubt in 78 cases, for deep invasion diagnosis
      in 148 cases and to define the invasion area in 346 cases. Placental MRI allowed
      accurate demarcation and assessment of the degree of placental invasion,
      parametrial involvement and cervico-trigonal vascular hyperplasia, permitting
      changes in the surgical tactical approach. Ultrasound and MRI differences were
      associated with placenta previa, uterine scar thinning and use of different
      criteria for placental invasion through definitions or terminology. Six cases of
      false-negative and 11 of false-positive findings were reported. CONCLUSION:
      Placental MRI provides excellent characterization of the degree and extension of
      placental invasion. Its usefulness in cases of adherent placentation is directly
      associated to the therapeutic measures, especially where dissection maneuvers are
      needed. Diagnostic differences between ultrasound and MRI related to the presence
      or not of placenta previa and uterine scar thinning.

PMID- 22881063
TI  - Chemistry and biology of genus Vismia.
AB  - CONTEXT: Many herbal remedies have been employed in the treatment and management
      of various human ailments since the beginning of human civilization. Vismia is an
      extensive genus of the family Hypericaceae and consists of small trees inhabiting
      the tropical and subtropical regions of South and Central America. Within the
      framework of an International Cooperative Biodiversity Groups project, three
      Vismia species were studied for their potential anticancer activity. OBJECTIVES:
      This review is an extensive study of the available scientific literature
      published and comprises of the ethnopharmacological, phytochemical and
      therapeutic potential of genus of plants under the umbrella Vismia. METHODS: The
      present review includes 134 natural products with 47 references compiled from the
      major databases, viz., Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr.
      Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An
      exhaustive survey of the accessed literature revealed that flavonoids, flavanols,
      xanthones, anthraones, anthraquinones, benzophenones, lignans, steroids,
      monoterpenes and triterpenes constituted the major classes of phytoconstituents
      of this genus. Pharmacological reports revealed that it is used for skin diseases
      such as dermatitis, leprosy, syphilis, herpes, scabies and eczemas, and as an
      anticancer for human breast, CNS, and lung cancer cell lines. CONCLUSION: Genus
      Vismia plants seem to hold great potential for an in-depth investigation towards
      discovering biological activities, especially for the treatment of cancers
      affecting our society. Through this review, the authors hope to attract the
      attention of natural product researchers throughout the world to focus on the
      unexplored potential of Vismia plants, with the view of developing new
      formulations with an improved therapeutic value.

PMID- 22881064
TI  - Development of a high-resolution melting-based approach for efficient
      differentiation among Bacillus cereus group isolates.
AB  - Strains belonging to Bacillus cereus Group include six different species, among
      which are Bacillus thuringiensis, Bacillus weihenstephanensis, and Bacillus
      cereus sensu stricto, a causative agent of food poisoning. Sequence of the panC
      housekeeping gene is used for B. cereus Group affiliation to seven major
      phylogenetic groups (I-VII) with different ecological niches and variations in
      thermal growth range and spore heat resistance of B. cereus Group microorganisms
      varies among phylogenetic groups. We assigned a selection of B. cereus sensu
      stricto strains related to food poisoning from the Spanish cultivar Collection
      (Valencia) to Group IV strains based on panC gene sequence. Thermal inactivation
      assays revealed variability of spore heat resistance within these Group IV
      strains. Adequate food sanitizing treatments therefore require fast and reliable
      identification of particular strains. In the present study, feasibility of
      genotyping via high-resolution melting (HRM) analysis was examined. HRM analysis
      of amplified polymorphic 16S-23 intergenic spacer region (ISR) region proved to
      be discriminatory for B. cereus sensu stricto strain typing, while two other
      polymorphic regions within the bacterial rRNA operon allowed differentiation
      between Bacillus species, demonstrating its applicability for discrimination on
      the species and strain level within B. cereus Group.

PMID- 22881065
TI  - Base-stacking-determined fluorescence emission of DNA abasic site-templated
      silver nanoclusters.
AB  - DNA-templated silver nanoclusters (Ag NCs) are emerging sets of fluorophores that
      are widely applicable because of high brightness, good photostability, and
      visible to near-infrared emissions tunable using the DNA sequence and length to
      change the NC size. We find that fluorescent Ag NCs can be size-selectively grown
      at DNA abasic sites (AP site) using a constrained duplex environment opposed by a
      cytosine and flanked by two guanines. The size of the AP site-grown Ag NCs is not
      affected by the increasing Ag(+) concentration. A Job's plot analysis shows that
      Ag(2) NCs are the species responsible for the observed emissions. Although
      varying the DNA sequence one base away from the AP site (i.e., the Ag NC growth
      site) does not alter the size of the fluorescent Ag NCs, the emissions of the
      formed Ag NCs are still gradually red shifted as the sequence changes from
      thymine (T) to cytosine (C), adenine (A), and guanine (G). Furthermore, this
      emission shift is strongly dependent on the base-stacking direction of the 3'
      side sequence of the 5'-G stack exactly flanking the AP site, which exhibits a
      larger emission alteration than altering the 5'-side sequence of the 3'-G stack
      flanking the AP site on the other side of the site. The excited-state lifetimes
      of the Ag NCs are inversely proportional to the singlet energies (DeltaE(0,0)) of
      the Ag NCs relative to their ground state and of the vertical ionization
      potentials of the guanines directly flanking the AP site as determined by the
      base stacking. All of these results support the conclusion that the Ag NC excited
      state becomes more stable by interacting with a guanine base because of the
      larger electronic dipole moment that can be modified by the stacked sequences.
      Additionally, the size of the formed Ag NCs seems to be dependent on the
      consecutive AP site number. Thus, the AP site design in this work provides an
      easy way to shed light on the role of DNA base stacking in the optical properties
      of Ag NCs.

PMID- 22881066
TI  - The International Workshop on Population Dynamics and Mathematical Biology was
      held at the historical CIRM. Introduction.

PMID- 22881067
TI  - A model for ovine brucellosis incorporating direct and indirect transmission.
AB  - In this work, we construct and analyse an ovine brucellosis mathematical model.
      In this model, the population is divided into susceptible and infected
      subclasses. Susceptible individuals can contract the disease in two ways: (i)
      direct mode - caused by contact with infected individuals; (ii) indirect mode -
      related to the presence of virulent organisms in the environment. We derive a net
      reproductive number and analyse the global asymptotic behaviour of the model. We
      also perform some numerical simulations, and investigate the effect of a
      slaughtering policy.

PMID- 22881068
TI  - Mathematical modelling and analysis of cellular signalling in macrophages.
AB  - Cell signalling pathways play a crucial role in proper cell development and
      behaviour, with implications to survival, chemotaxis, proliferation, and even
      programmed cell death known as apoptosis. In this article, we outline a
      mathematical model of the G-protein signalling pathway in a particular cell line
      of macrophages, focusing on activation of a particular G-protein-coupled
      receptor, P2Y(6). The model is based on the kinetics of P2Y(6) surface receptors,
      inositol trisphosphate, cytosolic calcium, and differential dynamics of multiple
      species of diacylglycerol. Insight into the dynamics of the system is given
      through recently available experimental results and incorporated into the model.
      Mathematical analysis of the model, including establishment of global existence,
      uniqueness, positivity, and boundedness of solutions, and global stability of a
      unique steady-state solution is discussed.

PMID- 22881069
TI  - Prion dynamics with size dependency-strain phenomena.
AB  - Models for the polymerization process involved in prion self-replication are well
      established and studied [H. Engler, J. Pruss, and G.F. Webb, Analysis of a model
      for the dynamics of prions II, J. Math. Anal. Appl. 324 (2006), pp. 98-117; M.L.
      Greer, L. Pujo-Menjouet, and G.F. Webb, A mathematical analysis of the dynamics
      of prion proliferation, J. Theoret. Biol. 242 (2006), pp. 598-606; J. Pruss, L.
      Pujo-Menjouet, G.F. Webb, and R. Zacher, Analysis of a model for the dynamics of
      prions, Discrete Cont. Dyn. Sys. Ser. B 6(1) (2006), pp. 215-225] in the case
      where the dynamics coefficients do not depend on the size of polymers. However,
      several experimental studies indicate that the structure and size of the prion
      aggregates are determinant for their pathological effect. This motivated the
      analysis in Calvez et al. [Size distribution dependence of prion aggregates
      infectivity, Math Biosci. 217 (2009), pp. 88-99] where the authors take into
      account size-dependent replicative properties of prion aggregates.   We first
      improve a result concerning the dynamics of prion aggregates when a pathological
      state exists (high production of the normal protein). Then we study the strain
      phenomena and more specifically we wonder what specific replicative properties
      are determinant in strain propagation. We propose to interpret it also as a
      dynamical property of size repartitions.

PMID- 22881070
TI  - A multi-scale model of erythropoiesis.
AB  - In this paper, a multi-scale mathematical model of erythropoiesis is proposed in
      which erythroid progenitors are supposed to be able to self-renew. Three cellular
      processes control erythropoiesis: self-renewal, differentiation and apoptosis. We
      describe these processes and regulatory networks that govern them. Two proteins
      (ERK and Fas) are considered as the basic proteins participating in this
      regulation. All erythroid progenitors are divided into several sub-populations
      depending on their maturity level. Feedback regulations by erythropoietin,
      glucocorticoids and Fas ligand (FasL) are introduced in the model. The model
      consists of a system of ordinary differential equations describing intracellular
      protein concentration evolution and cell population dynamics. We study steady
      states and their stability. We carry out computer simulations of an anaemia
      situation and analyse the results.

PMID- 22881071
TI  - The random walk of Azospirillum brasilense.
AB  - The bacterium Azospirillum brasilense has been frequently studied in laboratory
      experiments. It performs movements in space where long forward and backward runs
      on a straight line occur simultaneously with slow changes of direction of the
      line. A model is presented in which a correlated random walk on a line is joined
      to diffusion on a sphere of directions. For this transport system, a hierarchy of
      moment approximations is derived, ranging from a hyperbolic system with four
      dependent variables to a scalar damped wave equation (telegraph equation) and
      then to a single diffusion equation for particle density. The original parameters
      are compounded in the diffusion quotient. The effects of these parameters, such
      as particle speed or turning rate, on the diffusion coefficient are discussed in
      detail.

PMID- 22881072
TI  - Population collapse to extinction: the catastrophic combination of parasitism and
      Allee effect.
AB  - Infectious diseases are responsible for the extinction of a number of species. In
      conventional epidemic models, the transition from endemic population persistence
      to extirpation takes place gradually. However, if host demographics exhibits a
      strong Allee effect (AE) (population decline at low densities), extinction can
      occur abruptly in a catastrophic population crash. This might explain why species
      suddenly disappear even when they used to persist at high endemic population
      levels. Mathematically, the tipping point towards population collapse is
      associated with a saddle-node bifurcation. The underlying mechanism is the
      simultaneous population size depression and the increase of the extinction
      threshold due to parasite pathogenicity and Allee effect. Since highly pathogenic
      parasites cause their own extinction but not that of their host, there can be
      another saddle-node bifurcation with the re-emergence of two endemic equilibria.
      The implications for control interventions are discussed, suggesting that
      effective management may be possible for R(0)?1.

PMID- 22881073
TI  - Two models of interfering predators in impulsive biological control.
AB  - In this paper, we study the effects of Beddington-DeAngelis interference and
      squabbling, respectively, on the minimal rate of predator release required to
      drive a pest population to zero. A two-dimensional system of coupled ordinary
      differential equations is considered, augmented by an impulsive component
      depicting the periodic release of predators into the system. This periodic
      release takes place independently of the detection of the pests in the field. We
      establish the existence of a pest-free solution driven by the periodic releases,
      and express the global stability conditions for this solution in terms of the
      minimal predator rate required to bring an outbreak of pests to nil. In
      particular, we show that with the interference effects, the minimal rate will
      only guarantee eradication if the releases are carried out frequently enough.
      When Beddington-DeAngelis behaviour is considered, an additional constraint for
      the existence itself of a successful release rate is that the pest growth rate
      should be less than the predation pressure, the latter explicitly formulated in
      terms of the predation function and the interference parameters.

PMID- 22881074
TI  - Structure-property evaluation of thermally and chemically gelling injectable
      hydrogels for tissue engineering.
AB  - The impact of synthesis and solution formulation parameters on the swelling and
      mechanical properties of a novel class of thermally and chemically gelling
      hydrogels combining poly(N-isopropylacrylamide)-based thermogelling macromers
      containing pendant epoxy rings with polyamidoamine-based hydrophilic and
      degradable diamine cross-linking macromers was evaluated. Through variation of
      network hydrophilicity and capacity for chain rearrangement, the often
      problematic tendency of thermogelling hydrogels to undergo significant syneresis
      was addressed. The demonstrated ability to tune postformation dimensional
      stability easily at both the synthesis and formulation stages represents a
      significant novel contribution toward efforts to utilize poly(N
      isopropylacrylamide)-based polymers as injectable biomaterials. Furthermore, the
      cytocompatibility of the hydrogel system under relevant conditions was
      established while demonstrating time- and dose-dependent cytotoxicity at high
      solution osmolality. Such injectable in situ forming degradable hydrogels with
      tunable water content are promising candidates for many tissue-engineering
      applications, particularly for cell delivery to promote rapid tissue regeneration
      in non-load-bearing defects.

PMID- 22881075
TI  - "Flow valve" microfluidic devices for simple, detectorless, and label-free
      analyte quantitation.
AB  - Simplified analysis systems that offer the performance of benchtop instruments
      but the convenience of portability are highly desirable. We have developed novel,
      miniature devices that feature visual inspection readout of a target's
      concentration from a ~1 MUL volume of solution introduced into a microfluidic
      channel. Microchannels are constructed within an elastomeric material, and
      channel surfaces are coated with receptors to the target. When a solution is
      flowed into the channel, the target cross-links multiple receptors on the
      surface, resulting in constriction of the first few millimeters of the channel
      and stopping of flow. Quantitation is performed by measuring the distance
      traveled by the target solution in the channel before flow stops. A key advantage
      of our approach is that quantitation is accomplished by simple visual inspection
      of the channel, without the need for complex detection instrumentation. We have
      tested these devices using the model system of biotin as a receptor and
      streptavidin as the target. We have also characterized three factors that
      influence flow distance: solution viscosity, device thickness, and channel
      height. We found that solution capillary flow distance scales with the negative
      logarithm of target concentration and have detected streptavidin concentrations
      as low as 1 ng/mL. Finally, we have identified and evaluated a plausible
      mechanism wherein time-dependent channel constriction in the first few
      millimeters leads to concentration-dependent flow distances. Their simplicity
      coupled with performance makes these "flow valve" systems especially attractive
      for a host of analysis applications.

PMID- 22881076
TI  - [Screening of breast carcinoma screening in the Czech Republic requires
      cooperation with surgeons].
AB  - Mammographic screening is the only reliable method for reduction of mortality
      resulting from breast cancer. In the Czech Republic, a countrywide mammographic
      screening has been in function since 2003. Therefore, a total of 3 056 907 women
      underwent mammography examination by the end of 2010, with 14 914 breast cancers
      detected. Vast majority of the malignancies was in early stages with a good
      chance for effective therapy and excellent prognosis. During 2003-2009, regular
      and health insurance paid examinations were available to women aged 45-69. Since
      2010, the age range eligible for mammographic screening has been extended beyond
      the age of 69, with no upper limit. The rate of Czech women undergoing
      mammographic screening exceeded 50 percent already in 2008. The effectiveness of
      screening, increase of rates of early stages and reduction in breast cancer
      mortality rates have been regularly audited and evaluated based on data collected
      from all 70 Czech breast cancer screening units.

PMID- 22881077
TI  - [Malignant tumors of the esophagus in the Czech Republic].
AB  - INTRODUCTION: Data analysis of the incidence, mortality and basic data regarding
      therapy of esophageal cancer in the Czech Republic and determining possible ways
      to improve the current situation. MATERIAL AND METHODS: Analysis was performed
      using data obtained from the Czech National Cancer Registry and from the Registry
      of Thoracic Procedures from the Section of Thoracic Surgery of the Czech Surgical
      Society. Analysis of specialized literature provided generally accepted risk
      factors for the development of esophageal cancer. RESULTS: Esophageal cancer
      represents 0.7% of all solid malignant tumours in the Czech Republic (1.1% in
      males and 0.2% in females). During 1977 to 2008, the incidence increased from 2
      to 5.4 cases per 100.000 inhabitants and mortality from 1.9 to 4.1 cases per
      100.000 inhabitants. In absolute numbers, the incidence was 561 cases (5.4 per
      100.000 inhabitants) in 2008. Absolute mortality rate was 452 deaths (4.3 per
      100.000 inhabitants) and absolute prevalence (number of patients living with
      cancer or with its medical history) was 791 subjects(7.6 per 100.000
      inhabitants). When compared to international data, the incidence in the Czech
      Republic is the 84th highest in the world and 17th highest in Europe (mortality
      rates are at the 85th place in the world and the 18th place in Europe). In the
      Czech Republic, the highest incidence is in the Moravian-Silesian and Zlin
      regions (6.1 per 100.000), the lowest in the Plzen (4.2) and Vysocina (4.1)
      regions. The average age at the time of diagnosis is 62 years in males and 68
      years in females, the maximum incidence is between 55 and 69 years in males and
      between 58 and 79 years in females. Upon diagnosis, advanced stages of the
      disease predominate. In 2008, 28% of the detected esophageal cancer cases were
      stage I and II disorders, 60 % were stage III and IV disorders, and in 12% of the
      cases the stage was not determined. In the treated patient group, the five-year
      survival rate was 15.5% in total, based on an analysis of data from 2004 - 2007.
      The five-year survival was 30% in stage I and II diosease cases, 12% in stage III
      disorders and 2% in stage IV cases. When comparing the analysis of data from 2004
      to 2007 with the analysis of data from 2000 to 2003, there is a 10% improvement
      in stages I and II and a 4% improvement in stage III disorders. According to the
      Thoracic Surgery Registry of Thoracic Procedures data covering the period 2007 to
      2010, thoracic procedures are performed at 19 to 22 surgical departments,
      esophageal resections are performed at 13 to 14 surgical departments, but only in
      8 to 9 of these departments is the frequency of such procedures more than 10
      operations per year. At the authors' department, 53 esophageal resections have
      been performed in the past five years with a 3.8% postoperative mortality rate
      and a 23 % total postoperative morbidity rate. Forty-nine percent of the cases
      were adenocarcinomas. CONCLUSION: Based on its incidence in our population,
      esophageal cancer can be considered an unfrequent tumour. This analysis shows
      regions of the Czech Republic with higher incidence and the most at-risk age
      group in males. Significant risk factors for squamous cell cancer such as smoking
      and alcohol consumption have already been previously identified; in
      adenocarcinoma it is primarily Barrett's esophagus. Other risk groups include
      patients with achalasia and with strictures after corrosion injury to the
      esophagus. Acceptable treatment results may only be achieved in patients with
      less severe stages of the disease and it would therefore be appropriate to
      actively search for such patients in at-risk regions and among the risk groups as
      part of the preventive programs. To date, universally accepted guidelines for
      monitoring of such patients have not been defined. Surgical treatment is a highly
      specialized domain of thoracic surgeons focused on esophageal surgery and
      patients should be concentrated in specialized centres.

PMID- 22881078
TI  - [NOSE (Natural Orifice Specimen Extraction) in laparoscopic colorectal surgery].
AB  - INTRODUCTION: The aim of this study was to asses our initial first experience
      with NOSE techniques in laparoscopic colorectal surgery with both transanal and
      transvaginal extraction. MATERIAL AND METHODS: In this prospective study, the
      authors analyzed data from patients in whom NOSE laparoscopic sigmoid,
      rectosigmoid and rectal resections were performed in the Department of Surgery,
      University Hospital Ostrava, from May 2011 to October 2011. A group of 7 patients
      was analyzed based on demographic characteristics (sex,age and BMI). Tumor
      localization, type of extraction (transanal/transvaginal), the number of removed
      lymph nodes, tumor size, histology and length of the specimen were also assessed.
      Furthermore, the following intraoperative data were evaluated: duration of the
      procedure, frequency of intraoperative complications and conversion rate. During
      the postoperative period, duration of hospitalization and morbidity rates were
      evaluated. RESULTS: The patient group included 2 male (28.6%) and 5 female
      (71.4%) subjects, their median age was 70 years (61-80), BMI 26,76 (24.76-34.67).
      The pathology was located in the sigmoid colon in 4 cases (57.1%) and in the
      proximal rectum in 3 cases (42.9%). Transanal extraction was performed in 5
      patients (71.4%) and transvaginal extraction in 2 patients (28.6%). The average
      number of harvested lymph nodes was 13 (10-15), the average lenght of specimen
      was 16 cm (13-20) and the average tumor size was 4 cm (2-6). Histologically,
      adenocarcinoma was confirmed in 6 cases (85.7%), and low grade adenoma in 1 case
      (14.3%). The median duration of surgery was 205 min (140-300) and no
      intraoperative complications were recorded. No surgical conversion was required.
      No postoperative complications occured and the median duration of of hospital
      stay was 7 days (5-11). CONCLUSION: In the selected group of patients, NOSE
      technique proved to be a safe technique for laparoscopic colorectal procedures,
      reducing the risk of incisional complications while maintaining the principles of
      oncological radicality. Therefore, it may be considered a bridge towards NOTES
      (Natural Orifice Transluminal Endoscopic Surgery), surgery without scars.

PMID- 22881079
TI  - [Osteosynthetic material breakage in patients treated with DHS for proximal
      femoral fracture].
AB  - INTRODUCTION: In the literature, there are only few articles about the metal
      breakage after the Dynamic Hip Screw (DHS) osteosynthesis. We have evaluated our
      group of patients focusing on these specific complications. MATERIAL AND METHODS:
      We have evaluated a group of 428 patients (321 female and 107 male subjects) who
      underwent a total of 456 135 degrees 1"-collar DHS osteosyntheses, for primary
      proximal femoral fractures. The patients were aged 82.3 years on average, the
      procedures were performed during 1996-2009. We focused on the ostesynthetic
      material breakage (K-wire, sliding screw, hip plate, cortical screws). The follow
      up period was 2 years. RESULTS: Out of 16 DHS used for intracapsular femoral neck
      fractures, metal breakage was recorded in one case (6.25%)-(K-wire) and no
      reoperation was required. Out of a total of 436 DHS procedures performed for
      stable pertrochanteric fractures, metal breakage complications were recorded in 8
      cases (1.8%)-(3 times K-wire, 3 times cortical screws, 2 times sliding screw),
      and reoperation was indicated in 4 cases (2 times sliding screw, 2 times cortical
      screws). Out of a total of 4 DHS procedures used for subtrochanteric fractures,
      osteosynthetic material breakage was recorded in two cases (50%)-(1 times K-wire,
      1 times cortical screws) and no reoperation was required. No cases of hip plate
      breakage were recorded. Out of a total of all 456 DHS procedures metal breakage
      was recorded in 11 cases in total (2.4%), reoperation was required in 4 cases
      (0.9%). CONCLUSION: In the literature, the authors found only several articles
      related to the osteosynthetic material breakage after DHS surgery. Correct
      indication and operation technique can reduce occurence of this specific
      complication and the reoperation rates. In future, the authors plan to employ
      computer modelling methods and biomechanic analysis.

PMID- 22881080
TI  - [Restoration of active foot extension following peroneal nerve palsy].
AB  - INTRODUCTION: Common peroneal nerve palsy is the commonest lower extremity
      peripheral paresis. The foot drop and inability or difficulty to move the ankle
      and toes dorsally and inability to perform foot pronation is a debilitating
      condition for the patient. Tendon transfer is a treatment option often used to
      restore the foot function after the peroneal palsy in cases when reinervation is
      not clinically satisfactory. MATERIAL AND METHODS: The study group included 14
      patients treated in the Trauma department of FNO either for common or deep
      peroneal nerve paresis, or for isolated lesion of the anterior tibial muscle.
      Active muscles, i.e.the posterior tibial muscle (13 patients) or long peroneal
      muscle (1 patient) were used for the movement restoration procedure. The tendons
      were anchored to the cuneiform bone. RESULTS: In all the patients, active foot
      extension was restored, with the average range of motion of 12.3 degrees (4-20)
      and with sufficient muscle strength. Based on the Stanmore score assessment, the
      subjects showed good results, reaching 87-100 points. CONCLUSION: The posterior
      tibial muscle tendon transfer, or peroneus longus muscle tendon transfer lead to
      restoration of active extension of the foot. The reconstruction procedure results
      in a minor restriction of the ankle range of motion. Considering the foot
      functionality, it is better to perform the transfer with a slight preload of the
      tendon, in order to achieve adequate postoperative ankle extension.

PMID- 22881081
TI  - [Rates of complications after laparoscopic cholecystectomy depending on the
      coagulation technique--a comparative study].
AB  - INTRODUCTION: This study analyzes the impact of coagulation instrument devices
      used during gallbladder removal. Standard electrocautery is compared to the use
      of harmonic scapel. To determine whether the different principles of these
      instruments are the key to the frequency and severity of complications during
      laparoscopy. MATERIAL AND METHODS: Data collected from a statistically
      significant number of patients were evaluated and the experiment on porcine liver
      tissue was conducted to illustrate histopathological changes in tissues after the
      use of electrocautery and harmonic scalpel. RESULTS AND CONCLUSION: The presented
      data and the results of the experiment on animal liver tissue show that the use
      of harmonic scalpel during gallbladder removal is a safer technique with much
      lower risk of complications than the use of ordinary electrocautery.

PMID- 22881082
TI  - [Retrogastric bronchogenic cyst].
AB  - The authors present a case of an incidental finding of an asymptomatic
      retrogastricaly localized bronchogenic cyst. In a 3.5 year old boy, abdominal US,
      which was performed because of constipation complains, revealed a cystic mass.
      MRI study confirmed the presence of a simple cyst, located in the retrogastric
      region. The patient underwent laparotomy and the cyst, measuring 3 cm in a
      diameter, was removed from the omental bursa. During the postoperative period, no
      complications or symptoms were recorded. Histologicaly, the finding was
      surprisingly identified as a bronchogenic cyst. Occurence of bronchogenic cysts
      within the abdominal cavity is reported very rarely in the literature.

PMID- 22881083
TI  - Effect of hyperoxia and vascular occlusion on tissue oxygenation measured by near
      infra-red spectroscopy (InSpectraTM): a volunteer study.
AB  - Standard cardiorespiratory monitoring may fail to detect occult tissue ischaemia.
      This study assessed whether a near infra-red spectroscopy tissue oxygen
      saturation monitor (InSpectraTM) could detect progressive peripheral tissue
      ischaemia and whether hyperoxia may confound tissue oxygen saturation
      measurement. Tissue oxygen and arterial oxygen saturations were measured
      continuously in 30 healthy volunteers, first during a period of progressive
      increase in inspired oxygen concentration and subsequently during two periods of
      low- and high-pressure limb ischaemia. Increasing inspired oxygen concentration
      was associated with a small increase in mean (SD) tissue oxygen saturation of 5.3
      (7.1) %, reaching a plateau between 30% and 40% inspired oxygen. The rate and
      magnitude of decreases in tissue oxygen saturations were greater during high-
      than low-pressure ischaemia with a mean (SD) desaturation rate of 3.3 (0.9) vs
      1.8 (0.8) %.min(-1) (p<0.01). The dose-related association and lack of
      confounding by hyperoxia suggest that tissue oxygen saturation monitoring may be
      a useful adjunct to detect occult ischaemia.

PMID- 22881084
TI  - Oxidation resistance of iron and copper foils coated with reduced graphene oxide
      multilayers.
AB  - Protecting the surface of metals such as Fe and Cu from oxidizing is of great
      importance due to their widespread use. Here, oxidation resistance of Fe and Cu
      foils was achieved by coating them with reduced graphene oxide (rG-O) sheets. The
      rG-O-coated Fe and Cu foils were prepared by transferring rG-O multilayers from a
      SiO(2) substrate onto them. The oxidation resistance of these rG-O-coated metal
      foils was investigated by Raman spectroscopy, optical microscopy, and scanning
      electron microscopy after heat treatment at 200  degrees C in air for 2 h. The
      bare metal surfaces were severely oxidized, but the rG-O-coated metal surfaces
      were protected from oxidation. This simple solution process using rG-O is one
      advantage of the present study.

PMID- 22881116
TI  - Utility of metabolomics toward assessing the metabolic basis of quality traits in
      apple fruit with an emphasis on antioxidants.
AB  - A gas chromatography-mass spectrometry approach was employed to evaluate the use
      of metabolite patterns to differentiate fruit from six commercially grown apple
      cultivars harvested in 2008. Principal component analysis (PCA) of apple fruit
      peel and flesh data indicated that individual cultivar replicates clustered
      together and were separated from all other cultivar samples. An independent
      metabolomics investigation with fruit harvested in 2003 confirmed the separate
      clustering of fruit from different cultivars. Further evidence for cultivar
      separation was obtained using a hierarchical clustering analysis. An evaluation
      of PCA component loadings revealed specific metabolite classes that contributed
      the most to each principal component, whereas a correlation analysis demonstrated
      that specific metabolites correlate directly with quality traits such as
      antioxidant activity, total phenolics, and total anthocyanins, which are
      important parameters in the selection of breeding germplasm. These data sets lay
      the foundation for elucidating the metabolic basis of commercially important
      fruit quality traits.

PMID- 22881117
TI  - Laminated safety glass as an intermediate target: a wound ballistic study.
AB  - Various 9-mm ammunitions (A1, A4, A5, ST, GS, GSb, P.E.P., SeCa, HP, PTP/s, VM,
      McVG, DM41, PTP, SX2, PT, and MEN frangible) were tested regarding their
      velocity, energy, angle of impact, and potential wound channel after penetrating
      a car window at 30 degrees  and 90 degrees . Test materials were gelatine, soap,
      and pig cadavers. The velocities of the projectiles were between c. 288 and 430
      m/ses, the energy spread between 394 and 564 J. Handgun bullets fired through
      vehicular side window glass lose substantial energy reducing the effectiveness of
      the ammunition. This effect is greater when fired at an angle of 30 degrees 
      compared to 90 degrees . At a shooting angle of 90 degrees , none of the
      different projectiles showed remarkable differences considering its wound
      ballistic features. Accuracy is maintained at a 90 degrees  angle but seriously
      impaired at 30 degrees . None of the examined ammunition complied with the
      demanded wound channel effectiveness of 30-60 J/cm.

PMID- 22881118
TI  - Proteomic view of the venom from the fire ant Solenopsis invicta Buren.
AB  - Fire ants are well-known by their aggressive stinging behavior, causing many
      stinging incidents of medical importance. The limited availability of fire ant
      venom for scientific and clinical uses has restricted, up to now, the knowledge
      about the biochemistry, immunology, and pharmacology of these venoms. For this
      study, S. invicta venom was obtained commercially and used for proteomic
      characterization. For this purpose, the combination of gel-based and gel-free
      proteomic strategies was used to assign the proteomic profile of the venom from
      the fire ant S. invicta. This experimental approach permitted the identification
      of 46 proteins, which were organized into four different groups according to
      their potential role in fire ant venom: true venom components, housekeeping
      proteins, body muscle proteins, and proteins involved in chemical communication.
      The active venom components that may not present toxic roles were classified into
      three subgroups according to their potential functions: self-venom protection,
      colony asepsis, and chemical communication. Meanwhile, the proteins classified as
      true toxins, based on their functions after being injected into the victims'
      bodies by the fire ants, were classified in five other subgroups: proteins
      influencing the homeostasis of the victims, neurotoxins, proteins that promote
      venom diffusion, proteins that cause tissue damage/inflammation, and allergens.

PMID- 22881119
TI  - The adverse influence of attention-deficit disorder with or without hyperactivity
      on cognition in neurofibromatosis type 1.
AB  - AIM: A substantial proportion of patients with neurofibromatosis type 1 (NF1)
      have attention-deficit disorder with or without hyperactivity (AD[H]D). This
      study explored the influence of AD(H)D symptoms on the intellectual profile of
      patients with NF1. METHOD: We retrospectively analysed neuropsychological data
      from 114 children (66 males, 48 females; age range 6-16y; mean age 9y 3mo [SE
      3mo]) with NF1 from an NF1 outpatients department. Assessment included
      psychiatric diagnosis of AD(H)D (DSM-IV-TR criteria) and intelligence testing
      (Wechsler Intelligence Scale for Children, German version). Magnetic resonance
      images were available for all patients, intracranial findings being an exclusion
      criterion. The effects of AD(H)D symptoms on intelligence and on the cognitive
      profile were tested by analyses of variance. RESULTS: Patients with AD(H)D
      symptoms performed significantly worse than those without AD(H)D symptoms on all
      intelligence measures (main effects for Full-scale, Verbal, and Performance IQ;
      p<0.005). Subtests typically impaired in patients with NF1 (visuospatial skills
      and arithmetic) were not specifically influenced by AD(H)D symptoms. There were
      no differences between AD(H)D subtypes. INTERPRETATION: AD(H)D symptoms have a
      negative impact on the intellectual development of children with NF1. This impact
      seems to be of an unspecific nature, with a general attenuation of the cognitive
      profile.

PMID- 22881120
TI  - Multiferroic materials based on organic transition-metal molecular nanowires.
AB  - We report on the density functional theory aided design of a variety of organic
      ferroelectric and multiferroic materials by functionalizing crystallized
      transition-metal molecular sandwich nanowires with chemical groups such as -F, 
      Cl, -CN, -NO(2), ?O, and -OH. Such functionalized polar wires exhibit molecular
      reorientation in response to an electric field. Ferroelectric polarizations as
      large as 23.0 MUC/cm(2) are predicted in crystals based on fully hydroxylized
      sandwich nanowires. Furthermore, we find that organic nanowires formed by
      sandwiching transition-metal atoms in croconic and rhodizonic acids,
      dihydroxybenzoquinone, dichloro-dihydroxy-p-benzoquinone, or benzene decorated by
      -COOH groups exhibit ordered magnetic moments, leading to a multiferroic
      organometallic crystal. When crystallized through hydrogen bonds, the microscopic
      molecular reorientation translates into a switchable polarization through proton
      transfer. A giant interface magnetoelectric response that is orders of magnitude
      greater than previously reported for conventional oxide heterostructure
      interfaces is predicted.

PMID- 22881121
TI  - Ligand-controlled growth of ZnSe quantum dots in water during Ostwald ripening.
AB  - A strong ligand effect was observed for the aqueous-phase growth of ZnSe quantum
      dots (QDs) in the Ostwald ripening (OR) stage. The QDs were made by injecting Se
      monomer at room temperature followed by a ramp to 100  degrees C. The ramp
      produced a second, more gradual increase in the concentrations of both Zn and Se
      monomers fed by the dissolution of QDs below the critical size. The dissolution
      process was followed using measurements of the mass of Zn in QDs and in the
      supernatant by inductively coupled plasma optical emission spectroscopy (ICP
      OES). Despite the flux of monomers, there was little growth in the QDs of average
      size based on UV-vis absorption spectra, until the temperature reached 100 
      degrees C, when there was a period of rapid growth followed by a period of linear
      growth. The linear growth stage is the result of OR as the total mass of Zn in
      QDs and in the solvent remained constant. The growth data were fit to a continuum
      model for the limiting case of surface reaction control. The rate is proportional
      to the equilibrium coefficient for ligand detachment from the QD surface. The
      ligand 3-mercaptopropionic acid (MPA) was the most tightly bound to the surface
      and produced the lowest growth rate of (1.5-2) * 10(-3) nm/min in the OR stage,
      whereas thiolactic acid (TLA) was the most labile and produced the highest growth
      rate of 3 * 10(-3) nm/min. Methyl thioglycolate (MTG) and thioglycolic acid (TGA)
      produced rates in between these values. Ligands containing electron-withdrawing
      groups closer to the S atom and branching promote growth, whereas longer,
      possibly bidendate, ligands retard it. Mixed ligand experiments confirmed that
      growth is determined by ligand bonding strength to the QD. Photoluminescence
      spectroscopy showed that the more labile the ligand, the more facile the repair
      of surface defects during the exposure of the QDs to room light.

PMID- 22881122
TI  - Nanophotonic ionization for ultratrace and single-cell analysis by mass
      spectrometry.
AB  - Recent mechanistic studies have indicated that at subwavelength post diameters
      and selected aspect ratios nanopost arrays (NAPA) exhibit ion yield resonances (
      Walker  ,   B. N.     , Stolee  ,   J. A.     , Pickel  ,   D. L.     , Retterer 
      ,   S. T.     , and Vertes  ,   A. J. Phys. Chem. C     2010  ,   114  ,   4835 -
      4840  ). In this contribution we explore the analytical utility of these
      optimized structures as matrix-free platforms for laser desorption ionization
      mass spectrometry (LDI-MS). Using NAPA, we show that high ionization efficiencies
      enable the detection of ultratrace amounts of analytes (e.g., ~800 zmol of
      verapamil) with a dynamic range spanning up to 4 orders of magnitude. Due to the
      clean nanofabrication process and the lack of matrix material, minimal background
      interferences are present in the low-mass range. We demonstrate that LDI from
      NAPA ionizes a broad class of small molecules including pharmaceuticals, natural
      products, metabolites, and explosives. Quantitation of resveratrol in red wine
      samples shows that the analysis of targeted analytes in complex mixtures is
      feasible with minimal sample preparation using NAPA-based LDI. We also describe
      how multiple metabolite species can be directly detected in single yeast cells
      deposited on the NAPA chip. Twenty-four metabolites, or 4% of the yeast
      metabolome, were identified in the single-cell spectra.

PMID- 22881123
TI  - Laparoscopic versus open total mesorectal excision for middle and low rectal
      cancer: a meta-analysis of results of randomized controlled trials.
AB  - BACKGROUND: Laparoscopic total mesorectal excision (LTME) for rectal cancer
      remains controversial. The aim of this meta-analysis of randomized controlled
      trials (RCTs) is to compare LTME and open total mesorectal excision (OTME) as the
      primary treatment for patients with middle and low rectal cancer with regard to
      short-term outcomes. MATERIALS AND METHODS: Literature searches of electronic
      databases (PubMed, Embase, and the Cochrane Library) and manual searches up to
      October 30, 2011 were performed. Prospective randomized clinical trials were
      eligible if they included patients with middle and low rectal cancer treated by
      LTME versus OTME. Fixed and random effects models were used. Review Manager
      version 5.1 software was used for pooled estimates. RESULTS: Four RCTs enrolling
      624 participants (LTME group, 308 cases; OTME group, 316 cases) were included in
      the meta-analysis. LTME for rectal cancer was associated with a significantly
      longer operative time but significantly less intraoperative blood loss and
      earlier time to pass first flatus. We found no significant differences in the
      number of lymph nodes, overall morbidity, and perioperative mortality rates
      between the two groups. Time to resume liquid diet, time to resume normal diet,
      and length of hospital stay, although not significantly different between the two
      groups, did suggest a positive trend toward LTME. CONCLUSIONS: It may be
      concluded that LTME is a safe and effective alternative to OTME and is
      justifiable under the setting of clinical trials. Additional RCTs that compare
      LTME and OTME and investigate the long-term oncological outcomes of LTME are
      required to determine the advantages of LTME over OTME.

PMID- 22881125
TI  - Micropatterning of polymer brushes: grafting from dewetting polymer films for
      biological applications.
AB  - In this novel platform, a micropatterned polymer brush was obtained by grafting
      poly(poly(ethylene glycol) methyl ether methacrylate) (poly(PEGMA)) from a thin
      macroinitiator film using atom transfer radical polymerization (ATRP). A pattern
      of holes was formed in the macroinitiator film by taking advantage of its
      spontaneous dewetting above the glass transition temperature from a bottom
      polystyrene film, driven by unfavorable intermolecular forces. Patterning by
      dewetting can be achieved at length-scales from a few hundred nanometers to
      several tens of micrometers, by simply thermally annealing the bilayer above the
      glass transition temperature of the polymer. This approach is substrate
      independent, as polymer films can be cast onto surfaces of different size, shape,
      or material. As a demonstration of its potential, proteins, and individual cells
      were attached on targeted bioadhesive polystyrene areas of the micropatterns
      within poly(PEGMA) protein-repellent brushes. We anticipate this approach will be
      suitable for the patterning of brushes, especially for biomedical applications
      such as in the study of single cells and of cell cocultures.

PMID- 22881126
TI  - The tyrphostin AG1478 augments oridonin-induced A431 cell apoptosis by blockage
      of JNK MAPK and enhancement of oxidative stress.
AB  - Oridonin, a diterpenoid compound, extracted and purified from Rabdosia rubescen
      has been reported to have cytotoxic effect on tumour cells through apoptosis, and
      tyrosine kinase pathways are involved in these processes. A specific epidermal
      growth factor receptor (EGFR) inhibitor AG1478 was used to examine the
      relationship between EGFR signal pathways and oridonin-induced apoptosis and
      autophagy in EGFR abundant human epidermoid carcinoma A431 cells. Inhibition of
      EGFRaugmented oridonin-induced A431 cell apoptosis, while the changes of
      expression of downstream proteins, Bcl-2, Bcl-xL, Bax, cytochrome c, pro-caspase
      3, Fas, FADD and pro-caspase-8 suggested that both the intrinsic and extrinsic
      apoptotic pathways are involved in these processes. Pretreatment with AG1478
      aggravated oridonin-induced loss of mitochondrial membrane potential (MMP) and
      increased ROS generation in A431 cells, while a ROS scavenger, N-acetylcysteine
      (NAC) completely reversed oridonin- and AG1478-induced ROS generation and
      apoptosis. Therefore, AG1478 augmented oridonin-induced apoptosis by enhancing
      oxidative stress. Pretreatment with AG1478 decreased the expression of downstream
      MAPK proteins ERK, JNK and P38 and their phosphorylated forms to varying degrees
      compared with oridonin alone treatment. Then after administration of ERK, JNK and
      P38 inhibitors, only JNK inhibitor SP600125 effectively augmented oridonin
      induced apoptosis and ROS generation. Therefore, in EGFR downstream pathways, JNK
      played a major role in preventing oridonin-induced apoptosis. Autophagy
      antagonised apoptosis and exerted a protective effect in A431 cells, and both
      AG1478 and SP600125 decreased oridonin-induced autophagy. Inhibition of EGFR
      augmented oridonin-induced apoptosis and this was caused by enhanced oxidative
      stress, and JNK played a major protective role by increasing autophagy, leading
      to antagonising apoptosis and ROS generation.

PMID- 22881127
TI  - Structural analysis of Pla protein from the biological warfare agent Yersinia
      pestis: docking and molecular dynamics of interactions with the mammalian
      plasminogen system.
AB  - Yersinia pestis protein Pla is a plasmid-coded outer membrane protein with
      aspartic-protease activity. Pla exhibits a plasminogen (Plg) activator activity
      (PAA) that promotes the cleavage of Plg to the active serine-protease form called
      plasmin. Exactly how Pla activates Plg into plasmin remains unclear. To
      investigate this event, we performed the interactions between the predicted Plg
      and Pla protein structures by rigid-body docking with the HEX program and
      evaluated the complex stability by molecular dynamics (MD) using the GROMACS
      package programs. The predicted docked complex of Plg-Pla shows the same
      interaction site predicted by experimental site-direct mutagenesis in other
      studies. After a total of 8 ns of MD simulation, we observed the relaxation of
      the beta-barrel structure of Pla and the progressive approximation and
      stabilization between the cleavage site of Plg into the extracellular loops of
      Pla, followed by the increase in the number of H bonds. We also report here the
      aminoacids that participate in the active site and the sub sites of interaction.
      The total understanding of these interactions can be an important tool for drug
      design against bacterial proteases.

PMID- 22881128
TI  - Myeloid cells in tumour-immune interactions.
AB  - Despite highly developed specific immune responses, tumour cells often manage to
      escape recognition by the immune system, continuing to grow uncontrollably.
      Experimental work suggests that mature myeloid cells may be central to the
      activation of the specific immune response. Recognition and subsequent control of
      tumour growth by the cells of the specific immune response depend on the balance
      between immature (ImC) and mature (MmC) myeloid cells in the body. However,
      tumour cells produce cytokines that inhibit ImC maturation, altering the balance
      between ImC and MmC. Hence, the focus of this manuscript is on the study of the
      potential role of this inhibiting mechanism on tumour growth dynamics. A
      conceptual predator-prey type model that incorporates the dynamics and
      interactions of tumour cells, CD8(+) T cells, ImC and MmC is proposed in order to
      address the role of this mechanism. The prey (tumour) has a defence mechanism
      (blocking the maturation of ImC) that prevents the predator (immune system) from
      recognizing it. The model, a four-dimensional nonlinear system of ordinary
      differential equations, is reduced to a two-dimensional system using time-scale
      arguments that are tied to the maturation rate of ImC. Analysis shows that the
      model is capable of supporting biologically reasonable patterns of behaviour
      depending on the initial conditions. A range of parameters, where healing without
      external influences can occur, is identified both qualitatively and
      quantitatively.

PMID- 22881129
TI  - Nonlinear stability analyses of vegetative pattern formation in an arid
      environment.
AB  - The development of spontaneous stationary vegetative patterns in an arid
      isotropic homogeneous environment is investigated by means of various weakly
      nonlinear stability analyses applied to the appropriate governing equation for
      this phenomenon. In particular, that process can be represented by a fourth-order
      partial differential time-evolution logistic equation for the total plant biomass
      per unit area divided by the carrying capacity of its territory and defined on an
      unbounded flat spatial domain. Those patterns that consist of parallel stripes,
      labyrinth-like mazes, rhombic arrays of rectangular patches, and hexagonal
      distributions of spots or gaps are generated by the balance between the effects
      of short-range facilitation and long-range competition. Then those theoretical
      predictions are compared with both relevant observational evidence and existing
      numerical simulations as well as placed in the context of the results from some
      recent nonlinear pattern formation studies.

PMID- 22881130
TI  - Depletion of forestry resource biomass due to industrialization pressure: a ratio
      dependent mathematical model.
AB  - A model for interactions between forestry biomass, wildlife population and
      industrialization pressure is proposed and analysed. Here, the functional
      responses are assumed to be ratio-dependent type. The effect of forestry biomass
      depletion in a forested habitat caused by industrialization pressure on the
      survival of the forestry biomass dependent wildlife species is studied. The
      behaviours of the system near all ecological feasible equilibria are analysed.

PMID- 22881131
TI  - Population models with Allee effect: a new model.
AB  - In this paper, we develop several population models with Allee effects. We start
      by defining the Allee effect as a phenomenon in which individual fitness
      increases with increasing density. Based on this biological assumption, we
      develop several fitness functions that produce corresponding models with Allee
      effects. In particular, a rational fitness function yields a new mathematical
      model, which is the focus of our study. Then we study the dynamics of 2-periodic
      systems with Allee effects and show the existence of an asymptotically stable 2
      periodic carrying capacity.

PMID- 22881132
TI  - Dynamics of an age-structured population with Allee effects and harvesting.
AB  - We propose a discrete-time, age-structured population model to study the impact
      of Allee effects and harvesting. It is assumed that survival probabilities from
      one age class to the next are constants and fertility rate is a function of
      weighted total population size. Global extinction is certain if the maximal
      growth rate of the population is less than one. The model can have multiple
      attractors and the asymptotic dynamics of the population depend on its initial
      distribution if the maximal growth rate is larger than one. An Allee threshold
      depending on the components of the unstable interior equilibrium is derived when
      only the last age class can reproduce. The population becomes extinct if its
      initial population distribution is below the threshold. Harvesting on any
      particular age class can decrease the magnitude of the possible stable interior
      equilibrium and increase the magnitude of the unstable interior equilibrium
      simultaneously.

PMID- 22881133
TI  - Training lay counsellors to provide psychosocial support to ART users: successes
      and failures.
AB  - This study reports on a pilot project to train eight patient advocates (PAs) who
      provided psychosocial support to users of antiretroviral therapy (ART) in basic
      counselling skills. PAs received 18 hours of training over the course of 3
      months. A cadre of raters evaluated the PAs after the training using the
      Counsellor Rating Form and a Counsellor Evaluation Form. Counsellor activities
      that were rated as approaching acceptability were: reflection of content,
      encouraging, summarising, gathering data, exploring alternatives, giving
      directives and terminating the session. Counselling activities rated as requiring
      further training were reflection of feeling, interpretation, exploring logical
      consequences, confrontation, identifying positive assets and challenging. These
      results are discussed in the context of creating and sustaining a health-enabling
      community for ART users.

PMID- 22881137
TI  - The effect of beta-2 adrenergic receptor haplotype variations on the haemodynamic
      response following spinal anaesthesia for caesarean delivery.
AB  - We investigated whether genetic variations of the beta-2 adrenergic receptor
      (ADRB2) modulate the haemodynamic response following spinal anaesthesia for
      caesarean delivery. We focused on the effects of haplotypes formed by
      combinations of the Arg16Gly and Gln27Glu polymorphisms. Clinical data from 143
      healthy parturients were collected. Only the ArgGln haplotype appeared to
      influence the risk of hypotension, most probably through a recessive mode of
      inheritance (p=0.027). Therefore, patients were grouped according to ArgGln
      homozygosity in two groups: presence of one or no copies of the haplotype (n=120)
      or two copies of the haplotype (n=23). Both groups presented similar baseline
      characteristics. Comparatively, patients homozygous for the ArgGln haplotype
      presented consistently higher blood pressure levels throughout the evaluation
      period (p=0.001 for systolic arterial pressure variation from baseline). In
      conclusion, our results demonstrate that haplotype variations of the the ADRB2
      modulate the haemodynamic response following spinal anaesthesia for caesarean
      delivery.

PMID- 22881138
TI  - In vivo and in vitro hemostatic activity of Chromolaena odorata leaf extract.
AB  - CONTEXT: Chromolaena odorata (L.) R.M.King & H.Rob. (Asteraceae) or Siam weed has
      long been used to stop bleeding in Thailand and many countries. Only the aqueous
      leaf extract was investigated in in vivo and there have been conflicting results
      of in vitro hemostatic mechanisms of this plant. OBJECTIVE: The most appropriate
      C. odorata leaf extract that promoted the highest hemostatic activity and the
      hemostatic mechanisms of these plant extracts will be investigated. MATERIALS AND
      METHODS: The lyophilized aqueous leaf extract and alcoholic (50, 70, and 95%
      ethanol) extracts from the fresh and dried leaves were investigated both in vivo
      and in vitro. The bleeding time in male Wistar rats was measured to investigate
      the hemostatic effect. The hemostatic mechanisms were tested using in vitro
      platelet aggregation and blood coagulation tests in sheep plasma. RESULTS: All
      extracts displayed significantly reducing bleeding time (<2.5 min) in rats but
      did not induce platelet aggregation or blood clotting in the in vitro study. The
      in vitro blood clotting times of all extracts were >0.6 min. Ethanol extract
      (70%) from the dried leaves proved to be the extract producing the highest
      hemostatic activity in vivo with the bleeding time of 1.85 min. DISCUSSION AND
      CONCLUSION: The in vivo study with rats confirmed the significant ability of this
      plant extract to stop bleeding. However, the sufficient amount of calcium and
      active compounds which are aggregating and clotting agents to enhance blood
      coagulation and platelet aggregation in in vitro tests should be further studied.

PMID- 22881139
TI  - Role of Blepharis maderaspatensis and Ammannia baccifera plant extracts on in
      vitro oxygen radical scavenging, secretion of gastric fluid and gastroprotection
      on ulcer induced rats.
AB  - CONTEXT: Blepharis maderaspatensis L. Roth (BM) (Acanthaceae) and Ammannia
      baccifera L. (AB) (Lythraceae) are used in folk medicine for various stomach
      disorders. OBJECTIVE: The chloroform and ethanol extracts of both plants were
      evaluated for antioxidant, gastric antisecretory, and gastroprotective
      properties. METHODS: Antioxidant properties of the extracts were evaluated using
      2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and nitric oxide
      (NO) scavenging assay. The gastric antisecretory properties of the extracts were
      assessed, at a dose of 100 and 200 mg/kg, using aspirin-pylorus ligation induced
      gastric ulcer models and the gastroprotective activity of the extracts was
      assessed, at a dose of 100 and 200 mg/kg, using HCl-ethanol induced ulcer models
      in rats. RESULTS AND DISCUSSION: Ethanol extract of BM (EBM) possessed good
      antioxidant property with IC50 values of 37.4 and 44.1 ug/mL in DPPH and NO
      scavenging assays respectively, where 25-250 ug/mL concentration in DPPH assay
      and 30-300 ug/mL concentration in NO scavenging assay were used. Ethanol extract
      of AB (EAB) at a dose of 200 mg/kg reduced the free acidity to 142.66 mEq/L and
      total acidity to 451.22 mEq/L. It reduced the gastric secretion with increase in
      pH from 2.2 to 3.15. Possessing good antisecretory activity, it also reduced the
      ulcer by 92.2% in aspirin and pylorus ligation induced gastric ulcer models. EAB
      increased the mucus secretion and adherent mucus in the tissues with a 71.43%
      reduction of ulcerin HCl-ethanol induced ulcer models, at a dose of 200 mg/kg.
      This activity can be attributed to the various flavonoids like rutin and
      kaempferol-3-O-beta-glucopyranoside, and the phytosterol, beta-sitosterol-3-O
      beta-glucopyranoside, and phenolics present in the extracts. CONCLUSION: EBM
      possessed significant antioxidant property while EAB possessed good antisecretory
      and gastroprotective activity.

PMID- 22881140
TI  - Ethno medicinal survey of plants used by the indigenes of Rivers State of
      Nigeria.
AB  - CONTEXT: The medicinal plants used in the traditional medicine of Rivers State of
      Nigeria were surveyed. OBJECTIVE: The survey aims to identify and document the
      plants used amongst the indigenes of Rivers State. MATERIALS AND METHODS: Semi
      structured interviews were conducted during a field trip to gather information
      from traditional medical practitioners (TMPs) and community elders. RESULTS:
      Medicinal plant species (188) representing 169 genera and 82 families used in the
      ethno medicine of the people of Rivers State were recorded from 460 households.
      The most represented genera were Ipomoea and Citrus providing four species each.
      The most important species showed the highest Fidelity level (FL) value and these
      included Ageratum conyzoides L. (Asteraceae) (100%) and Tridax procumbens L.
      (Asteraceae) (100%). The most important categories of diseases were those that
      showed the highest Informant consensus factor (ICF) value of 0.99, such as dermal
      or digestive problems and fever/malaria. The most used plant part was leaves
      (42%), while decoction was the main method of drug preparation (36%). DISCUSSION
      AND CONCLUSION: The survey shows that more than half of the medicinal plants
      gathered in Rivers State are also used in other countries of the world for
      various ailments. The high values of ICF recorded indicate high degree of
      agreement among the informants, while the high FL values suggest the popular use
      of the plants. The survey provides a useful source of information for TMPs and
      medicinal plant researchers. These medicinal plants gathered may bring about drug
      discovery and may also be incorporated into the healthcare delivery system of the
      country.

PMID- 22881141
TI  - A botulinum neurotoxin-like function of Potentilla chinensis extract that
      inhibits neuronal SNARE complex formation, membrane fusion, neuroexocytosis, and
      muscle contraction.
AB  - CONTEXT: Botulinum neurotoxins (BoNTs) are popularly used to treat various
      diseases and for cosmetic purposes. They act by blocking neurotransmission
      through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE) proteins. Recently, several polyphenols were shown to
      interfere with SNARE complex formation by wedging into the hydrophobic core
      interface, thereby leading to reduced neuroexocytosis. OBJECTIVE: In order to
      find industrially-viable plant extract that functions like BoNT, 71 methanol
      extracts of flowers were screened and BoNT-like activity of selected extract was
      evaluated. MATERIALS AND METHODS: After evaluating the inhibitory effect of 71
      flower methanol extracts on SNARE complex formation, seven candidates were
      selected and they were subjected to SNARE-driven membrane fusion assay.
      Neurotransmitter release from neuronal PC12 cells and SNARE complex formation
      inside the cell was also evaluated. Finally, the effect of one selected extract
      on muscle contraction and digit abduction score was determined. RESULTS: The
      extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower
      inhibited neurotransmitter release from neuronal PC12 cells by approximately 90%
      at a concentration of 10 MUg/mL. The extract inhibited neuroexocytosis by
      interfering with SNARE complex formation inside cells. It reduced muscle
      contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which
      is comparable to the action of the Ca2+-channel blocker verapamil and BoNT type
      A. DISCUSSION AND CONCLUSION: While BoNT blocks neuroexocytosis by cleaving SNARE
      proteins, the Potentilla chinensis extract exhibited the same activity by
      inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently
      as BoNT, suggesting the potential versatility in cosmetics and therapeutics.

PMID- 22881142
TI  - Investigation of optimal extraction, antioxidant, and antimicrobial activities of
      Achillea biebersteinii and A. wilhelmsii.
AB  - OBJECTIVE: Achillea species are endowed with multiple biological activities
      including antioxidant properties. However, no study has yet investigated the
      impact of extraction method and pH on the biological activities of these plants.
      The present study aimed to investigate the antioxidant and antimicrobial effects
      of methanol extracts from the aerial parts of the species Achillea biebersteinii
      Afan and Achillea wilhelmsii C. Koch (Asteraceae). In addition, the impact of
      extraction method and pH on these biological activities was evaluated. MATERIALS
      AND METHODS: Methanol extracts of A. biebersteinii and A. wilhelmsii were
      prepared using classical maceration and high-intensity ultrasound methods.
      Ultrasound-assisted extraction was performed at three different pH values: 5.7,
      6.3 and 6.9. RESULTS: Total phenolic compounds (range: 20.16-108.54 vs. 17.18
      59.61 mg gallic acid equivalent/g sample in A. biebersteinii and A. wilhelmsii,
      respectively), total flavonoids (range: 8.33-12.97 vs. 7.79-9.41 mg catechin
      equivalent/g sample), 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity
      (IC50: 40.63-346.34 vs. 84.02-462.41) and reducing power (IC50: 504.44-4406.67
      vs. 1710.00-5501.67) were significantly higher in A. biebersteinii vs. A.
      wilhelmsii and ultrasound-assisted vs. classical maceration extracts of both
      species. The aforementioned items were higher at pH = 6.3, followed by pHs of 6.9
      and 5.7, respectively. Overall, A. biebersteinii extracts were more active
      against all of the tested microorganisms than A. wilhelmsii. Sensitivities of
      Gram-positive bacteria were higher for both Achillea extracts than the Gram
      negative bacteria. No observable inhibitory activity was found from different
      extracts against Aspergillus niger. CONCLUSION: The findings of the present study
      suggest that methanol extracts of A. biebersteinii and A. wilhelmsii possess
      antioxidant and antimicrobial activity, being higher in the former. Ultrasound
      assisted extraction and pH of 6.3 have significant augmenting impact on the total
      phenolic and flavonoid content as well as antioxidant activities of both species.

PMID- 22881143
TI  - Reducing effect of mangiferin on serum uric acid levels in mice.
AB  - CONTEXT: Mangiferin, a natural bioactive xanthone C-glycoside, is widely present
      in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has
      been reported that mangiferin possesses a variety of biological activities,
      including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and
      anticarcinogenic. OBJECTIVE: The hypouricemic effect and xanthine oxidoreductase
      (XOR) inhibitory activity of mangiferin were investigated here for the first
      time. MATERIALS AND METHODS: The hypouricemic effect of mangiferin was
      investigated in normal and hyperuricemic mice induced by potassium oxonate.
      Mangiferin at a dose of 0.75-100.0 mg/kg was given intragastrically to mice. The
      serum urate levels were determined using the phosphotungstic acid method. The
      hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in
      hyperuricemic mice were assayed using commercially available kits. RESULTS: The
      results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly
      reduced the serum urate levels (148.7 +/- 37.8, 142.2 +/- 44.5, 121.7 +/- 21.7
      ummol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8
      +/- 71.2 ummol/L). However, mangiferin did not decrease the serum urate levels in
      normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic
      activities of XDH in hyperuricemic mice were significantly decreased by
      mangiferin, while no changes of XOD were observed. Acute toxicity study in mice
      showed that mangiferin was very safe at a dose of up to 25 g/kg. DISCUSSION AND
      CONCLUSION: These findings demonstrate that mangiferin has the potential to be
      developed as a new therapeutic agent for the treatment of hyperuricemia and gout.

PMID- 22881145
TI  - Statement of retraction: "Larvicidal activity of 4-hydroxycoumarin derivatives
      against Aedes aegypti". Pharmaceutical Biology 2011 49:2, 190-3.

PMID- 22881144
TI  - Edematogenic activity of a sulfated galactan from the red marine algae Gelidium
      crinale.
AB  - CONTEXT: The red algae Gelidium crinale (Turner) Gaillon (Gelidiaceae),
      encountered along the Southeast and Northeast Brazilian sea coast, contains a
      sulfated galactan presenting a similar saccharide backbone compared to lambda
      carrageenan. Inflammatory effects of other galactans were reported, but not for
      that obtained from G. crinale (SG-Gc). OBJECTIVE: To investigate the in vivo
      edematogenic effect of SG-Gc in comparison to lambda carrageenan. METHODS: SG-Gc
      was isolated by ion exchange chromatography. Paw edema was induced by
      subcutaneous (s.c.) intraplantar injection of SG-Gc or lambda carrageenan and
      evaluated by hydroplethysmometry. Data were expressed as the increase in paw
      volume subtracted from the basal volume or area under curve-AUC. To investigate
      the participation of early and late-phase inflammatory mediators, rats were
      treated with pyrilamine, compound 48/80, indomethacin, NG-nitro-L-arginine methyl
      ester (L-NAME), or pentoxifylline before SG-Gc. RESULTS: SG-Gc edematogenic
      effect was initiated at 0.5 h, peaked at 2 h (1.26 +/- 0.05 mL) and lasted until
      6 h (0.21 +/- 0.03 mL), whereas the carrageenan-induced edema started at 1 h. The
      first phase (1-3 h) of SG-Gc-induced edema was 176 +/- 15 (AUC) versus
      carrageenan (114.5 +/- 14), whereas the second phase (3-5 h) was 95 +/- 12 (AUC)
      versus carrageenan (117.5 +/- 11). Treatment with compound 48/80, pyrilamine,
      indomethacin, L-NAME, and pentoxifylline inhibited the effect of SG-Gc by 32, 40,
      69, 72, and 49%, respectively. DISCUSSION AND CONCLUSION: SG-Gc and lambda
      carrageenan induce different profile of inflammatory response in the paw edema
      model, that involves histamine, cytokines, prostaglandins, and nitric oxide (NO),
      but with different degree of participation.

PMID- 22881146
TI  - Syndecan-2 can promote clearance of T-cell receptor/CD3 from the cell surface.
AB  - T cells express the heparan sulphate proteoglycans syndecan-2 and syndecan-4.
      Syndecan-4 plays a T-cell inhibitory role; however, the function of syndecan-2 is
      unknown. In an attempt to examine this function, syndecan-2 was expressed
      constitutively in Jurkat T cells. Interestingly, the expression of syndecan-2
      decreased the surface levels of T-cell receptor (TCR)/CD3 complex, concomitant
      with intracellular retention of CD3epsilon and partial degradation of the TCR
      zeta chain. Immunofluorescence microscopy revealed that intracellular CD3epsilon
      co-located with Rab-4 endosomes. However, the intracellular pool of CD3epsilon
      did not recycle to the cell surface. The lower TCR/CD3 surface levels caused by
      syndecan-2 led to reduced TCR/CD3 responsiveness. We show that the cytosolic PDZ
      binding domain of syndecan-2 is not necessary to elicit TCR/CD3 down-regulation.
      These results identify a previously unrecognized means of controlling surface
      TCR/CD3 expression by syndecan-2.

PMID- 22881147
TI  - Fluorescence quenching studies of potential-dependent DNA reorientation dynamics
      at glassy carbon electrode surfaces.
AB  - The potential-dependent reorientation dynamics of double-stranded DNA (ds-DNA)
      attached to planar glassy carbon electrode (GCE) surfaces were investigated. The
      orientation state of surface-bound ds-DNA was followed by monitoring the
      fluorescence from a 6-carboxyfluorescein (FAM6) fluorophore covalently linked to
      the distal end of the DNA. Positive potentials (i.e., +0.2 V vs open circuit
      potential, OCP) caused the ds-DNA to align parallel to the electrode surface,
      resulting in strong dipole-electrode quenching of FAM6 fluorescence. Switching of
      the GCE potential to negative values (i.e., -0.2 V vs OCP) caused the ds-DNA to
      reorient perpendicular to the electrode surface, with a concomitant increase in
      FAM6 fluorescence. In addition to the very fast (submilliseconds) dynamics of the
      initial reorientation process, slow (0.1-0.9 s) relaxation of FAM6 fluorescence
      to intermediate levels was also observed after potential switching. These
      dynamics have not been previously described in the literature. They are too slow
      to be explained by double layer charging, and chronoamperometry data showed no
      evidence of such effects. Both the amplitude and rate of the dynamics were found
      to depend upon buffer concentration, and ds-DNA length, demonstrating a
      dependence on the double layer field. The dynamics are concluded to arise from
      previously undetected complexities in the mechanism of potential-dependent ds-DNA
      reorientation. The possible origins of these dynamics are discussed. A better
      understanding of these dynamics will lead to improved models for potential
      dependent ds-DNA reorientation at electrode surfaces and will facilitate the
      development of advanced electrochemical devices for detection of target DNAs.

PMID- 22881148
TI  - Laser-assisted simultaneous transfer and patterning of vertically aligned carbon
      nanotube arrays on polymer substrates for flexible devices.
AB  - We demonstrate a laser-assisted dry transfer technique for assembling patterns of
      vertically aligned carbon nanotube arrays on a flexible polymeric substrate. A
      laser beam is applied to the interface of a nanotube array and a polycarbonate
      sheet in contact with one another. The absorbed laser heat promotes nanotube
      adhesion to the polymer in the irradiated regions and enables selective pattern
      transfer. A combination of the thermal transfer mechanism with rapid direct
      writing capability of focused laser beam irradiation allows us to achieve
      simultaneous material transfer and direct micropatterning in a single processing
      step. Furthermore, we demonstrate that malleability of the nanotube arrays
      transferred onto a flexible substrate enables post-transfer tailoring of electric
      conductance by collapsing the aligned nanotubes in different directions. This
      work suggests that the laser-assisted transfer technique provides an efficient
      route to using vertically aligned nanotubes as conductive elements in flexible
      device applications.

PMID- 22881187
TI  - Are hips stable in children with cerebral palsy?

PMID- 22881188
TI  - Significantly reinforced composite fibers electrospun from silk fibroin/carbon
      nanotube aqueous solutions.
AB  - Microcomposite fibers of regenerated silk fibroin (RSF) and multiwalled carbon
      nanotubes (MWNTs) were successfully prepared by an electrospinning process from
      aqueous solutions. A quiescent blended solution and a three-dimensional Raman
      image of the composite fibers showed that functionalized MWNTs (F-MWNTs) were
      well dispersed in the solutions and the RSF fibers, respectively. Raman spectra
      and wide-angle X-ray diffraction (WAXD) patterns of RSF/F-MWNT electrospun fibers
      indicated that the composite fibers had higher beta-sheet content and
      crystallinity than the pure RSF electrospun fibers, respectively. The mechanical
      properties of the RSF electrospun fibers were improved drastically by
      incorporating F-MWNTs. Compared with the pure RSF electrospun fibers, the
      composite fibers with 1.0 wt % F-MWNTs exhibited a 2.8-fold increase in breaking
      strength, a 4.4-fold increase in Young's modulus, and a 2.1-fold increase in
      breaking energy. Cytotoxicity test preliminarily demonstrated that the
      electrospun fiber mats have good biocompatibility for tissue engineering
      scaffolds.

PMID- 22881189
TI  - Use of an artificial immune system derived method for the charge state assignment
      of small-molecule mass spectra.
AB  - Knowing the charge state of an ion in a mass spectrum is crucial to being able to
      assign a formula to it. For many small-molecule peaks in complex mass spectra,
      the intensities of the isotopic peaks are too low to allow the charge state to be
      calculated from isotopic spacings, which is the basis of the conventional method
      of determining the charge state of an ion. A novel artificial intelligence
      derived method for identifying the charge state of ions, in the absence of any
      isotopic information or a series of charge states, has been developed using an
      artificial immune system approach. This technique has been tested against
      synthetic and real data sets and has proven successful in identifying the
      majority of multiply charged ions, thereby significantly improving the peak
      assignment rate and confidence.

PMID- 22881190
TI  - Effect of processing and cooking conditions on onion (Allium cepa L.) induced
      antiplatelet activity and thiosulfinate content.
AB  - Allium  vegetables serve as sources of antiplatelet agents that may contribute to
      the prevention of cardiovascular disease. However, onion and garlic, the major 
      Allium  species, are usually cooked before consumption. Here, we examined the
      effect of cooking on onion in vitro antiplatelet activity (IVAA). Two different
      cooking systems (convection oven and microwaves) and several time-temperature
      variables were tested on whole bulbs, quarters of bulbs, and completely crushed
      bulbs, monitoring the degradation of sulfur antiplatelet compounds (e.g.,
      thiosulfinates) by analysis of pyruvate levels. Although heating was, in general,
      detrimental for onion IVAA, the extent of this effect varied greatly, from
      unaffected antiplatelet activity (AA) (i.e., similar to raw onion) to a complete
      lost of activity, depending upon the manner in which onions were prepared prior
      to heating, the cooking method, and the intensity of the heat treatment. "Whole",
      "quarters", and "crushed" onions lost their IVAA after 30, 20, and 10 min of oven
      heating, respectively. The longer retainment of AA in intact bulbs was attributed
      to a later alliinase inactivation. Proaggregatory effects observed in samples
      subjected to the most intense oven and microwave heat treatments suggest that
      extensively cooked onions may stimulate rather than inhibit platelet aggregation.
      The efficacy of  Allium  species as antiplatelet agents, as affected by
      preparation and cooking conditions, is discussed.

PMID- 22881191
TI  - Alcohol dependence and criminal behavior: preliminary results of an association
      study of environmental and genetic factors in an Italian male population.
AB  - The aim of this study is to propose an innovative approach evaluating the
      connection between alcohol use disorders and criminal behavior. The research,
      structured as a case-control study, was based on the analysis of environmental
      (social variables) and genetic factors (single nucleotide polymorphisms of
      glutamic acid decarboxylase) in a population (N = 173) of Italian alcohol
      dependent men. Group 1 (N = 47, convicted subjects) was compared with Group 2 (N
      = 126, no previous criminal conduct). Grade repetition, work problems, and drug
      problems were statistically associated with criminal behavior. Having daily
      family meals together and having children were inversely related to convictions.
      The genotype distribution of the two groups was similar. The association between
      environmental factors and antisocial behavior confirms previous findings in the
      literature. The lack of genetic association does not exclude the role of the
      gamma-aminobutyric acid (GABA) system in determining antisocial behavior; further
      studies with larger samples are needed, together with investigation of other
      components of the GABA pathway.

PMID- 22881192
TI  - Successful long-term enzyme replacement therapy in a young adult with Fabry
      disease.

PMID- 22881193
TI  - Exploration of the binding of DNA binding ligands to Staphylococcal DNA through
      QM/MM docking and molecular dynamics simulation.
AB  - DNA binding ligands (DBL) were reported to bind the minor groove of bacterial
      DNA. In the present study, DBL were analyzed and screened for their
      Staphylococcus inhibitory activity by inhibiting the Staphylococcal DNA
      replication. The orientation and the ligand-receptor interactions of DBL within
      the DNA-binding pocket were investigated applying a multi-step docking protocol
      using Glide and QM/MM docking. The polarization of ligands with QM/MM for DNA
      ligand docking with Staphylococcal DNA minor groove was performed in order to
      understand their possible interactions. Molecular dynamics simulation techniques
      were employed to obtain the dynamic behavior of the DBL with Staphylococcal DNA.
      Computational docking and simulation represented a promising alternative to
      bridge the gap, and so that DNA and gyrase interactions were blocked by DBL. The
      results revealed the importance of the DBL for strong interactions with the DNA
      minor groove region and blocking the bacterial replication.

PMID- 22881194
TI  - Depression in rural adolescents: relationships with gender and availability of
      mental health services.
AB  - INTRODUCTION: There is growing evidence in the literature which indicates that
      the prevalence of depression is similar in both non-metropolitan and metropolitan
      areas. However, it is generally perceived that factors associated with
      compromised mental health in rural residents include deprivation and lack of
      access to healthcare services. This study examines the relationship between
      depression and possible determinants of mental health among rural adolescents.
      The determinants identified were degree of remoteness, gender, socioeconomic
      status and the perception of rural community characteristics. Rural community
      characteristics examined were long waiting lists and lack of mental health
      professionals. METHOD: Respondents were 531 South Australian adolescents (55.7%
      female) aged 13 to 18 years, living outside the Adelaide (state capital)
      metropolitan area. Respondents completed a questionnaire including: demographic
      questions; the Kutcher Adolescent Depression Scale (KADS); and questions
      regarding individual perceptions of community characteristics. The data were
      obtained by self-report, degree of remoteness was measured using the
      Accessibility and Remoteness Index of Australia Plus, and socio-economic status
      was determined from the Australian Bureau of Statistics (ABS) Socio-Economic
      Index of Relative Socio-Economic Advantage and Disadvantage (SEIFA). RESULTS: The
      rate of depression obtained from this sample of rural adolescents is concerning;
      18% screened positive for depression on the KADS, 41% reported low mood much of
      the time or more often, and 20% experienced occasional or more frequent self-harm
      or suicidal thoughts, plans or actions. Depression was related to gender, with
      more females (23%) screening positive for depression than males (11.8%).
      Prevalence of depression was unrelated to degree of remoteness or the
      socioeconomic status of the participants. This finding is not consistent with
      other research that identifies socioeconomic status as a psychosocial determinant
      of mental health. It is noteworthy that the perception of long waiting lists and
      a lack of mental health professionals were related to depression but that this
      relationship was only significant for females. This may be because those who
      experience symptoms of depression are more likely to be aware of service
      availability due to help-seeking behaviour. That this finding is significant for
      females is consistent with research that identifies females as being better able
      to identify symptoms of depression and more willing to seek help. CONCLUSION:
      Efforts to enhance the mental health of rural Australian adolescents should focus
      on improving the availability of mental health services, improving mental health
      literacy and promoting help-seeking behaviour for mental health difficulties.
      Consideration should be given to the gender differences identified when
      developing future mental health initiatives.

PMID- 22881195
TI  - Daily spiritual experiences, social support, and depression among elderly Korean
      immigrants.
AB  - OBJECTIVES: This study examined the associations of daily spiritual experiences
      (DSE) and social support with depression to find viable coping resources and
      enhance the quality of life among elderly Korean immigrants. METHOD: We used
      Smith's (2003) theory of religious effects and Baron and Kenny's (1986) approach
      for mediation analysis to explain the mediating role of social support between
      DSE and depression. The sample consisted of 200 elderly Korean immigrants who
      were aged 65 or older (mean age = 72.5, range = 65-89) living in the New York
      City Metropolitan area. Hierarchical regression model was used with SPSS version
      17.0 to analyze cross-sectional data. RESULTS: Elderly Korean immigrants in the
      present sample were found to be moderately engaged in DSE but not experiencing a
      fair level of social support. Respondents reported no depression on the average
      but 30% of them (60 out of 200 respondents) were experiencing mild to severe
      depression. Both DSE and social support were inversely related with depression,
      and the relationship between DSE and depression was mediated by social support.
      CONCLUSION: These findings are only suggestive and should not be generalized to a
      larger population. However, this study supports the importance of DSE and social
      support in the life of elderly Korean immigrants as a way to alleviate
      depression. Mental health professionals may consider facilitating social network
      when elderly Korean immigrants suffer from depression.

PMID- 22881196
TI  - Curvature sorting of peripheral proteins on solid-supported wavy membranes.
AB  - Cellular membrane deformation and the associated redistribution of membrane-bound
      proteins are important aspects of membrane function. Current model membrane
      approaches for studying curvature sensing are limited to positive curvatures and
      often require complex and delicate experimental setups. To overcome these
      challenges, we fabricated a wavy substrate by imposing a range of curvatures onto
      an adhering lipid bilayer membrane. We examined the curvature sorting of several
      peripheral proteins binding to the wavy membrane and observed them to partition
      into distinct regions of curvature. Furthermore, single-molecule imaging
      experiments suggested that the curvature sensing of proteins on low-curvature
      substrates requires cooperative interactions.

PMID- 22881197
TI  - Effects of expeller pressed camelina meal and/or canola meal on digestibility,
      performance and fatty acid composition of broiler chickens fed wheat-soybean meal
      based diets.
AB  - This experiment was conducted to compare the effects of graded levels of camelina
      meal and/or canola meal on digestibility, performance and fatty acid composition
      of broiler chickens. A total of 180-day-old male broiler chicks were randomly
      assigned to one of the six treatments. The control diet was based on wheat and
      soybean meal and contained 15% canola meal. The experimental diets contained 3%,
      6%, 9%, 12% or 15% camelina meal added at the expense of canola meal. Chromic
      oxide (0.35%) was added to all diets as a digestibility marker. On the morning of
      day 22, birds were killed by cervical dislocation and their abdominal fat pad was
      obtained. The apparent total tract digestibility of dry matter and energy as well
      as nitrogen retention all declined linearly (p < 0.01) with increasing levels of
      dietary camelina meal. Weight gain (p < 0.01) and feed intake (p = 0.08) were
      linearly reduced as the level of camelina meal in the diet increased. Feed
      conversion ratio was also negatively affected by camelina meal (p < 0.01). Birds
      fed diets containing 15% camelina meal had significantly higher (p < 0.01) levels
      of polyunsaturated fatty acids, total n-3 fatty acids, total n-6 fatty acids and
      a significantly lower ratio of n-6 to n-3 fatty acids (p < 0.01) than birds fed
      canola meal. In conclusion, the inclusion of camelina meal in their diet
      significantly reduced the growth and feed conversion ratio of broilers compared
      with canola meal. However, the potential to incorporate n-3 fatty acids into
      carcass tissues may provide some justification for including camelina meal in
      poultry rations.

PMID- 22881198
TI  - Characterization of fatty acid liposome coated with low-molecular-weight
      chitosan.
AB  - Preparation of chitosan-coated fatty acid liposomes is often restricted by the
      solubility of chitosan under basic conditions. In this experiment, the
      preparation of chitosan-coated oleic acid (OA) liposomes using low molecular
      weight (LMW) chitosan (10 and 25 kDA) was demonstrated. These selected LMW
      chitosans are water soluble. The coating of the chitosan layer on OA liposomes
      was confirmed by its microscope images and physicochemical properties, such as
      zeta potential and the size of the liposomes. The "peeling off" effect on the
      surface of chitosan-coated OA liposomes was observed in the atomic force
      microscope images and showed the occurrence of the chitosan layer on the surface
      of OA liposomes. The size of the chitosan-coated liposomes was at least 20 nm
      smaller than the OA liposomes, and the increase of zeta potential with the
      increasing amount of LMW chitosan further confirmed the presence of the surface
      modification of OA liposomes.

PMID- 22881199
TI  - Possible effects of mobilisation on acute post-operative pain and nociceptive
      function after total knee arthroplasty.
AB  - BACKGROUND: Experimental studies in animals, healthy volunteers, and patients
      with chronic pain suggest exercise to provide analgesia in several types of pain
      conditions and after various nociceptive stimuli. To our knowledge, there is no
      data on the effects of exercise on pain and nociceptive function in surgical
      patients despite early mobilisation being an important factor to enhance
      recovery. We therefore investigated possible effects of mobilisation on post
      operative pain and nociceptive function after total knee arthroplasty (TKA).
      METHODS: Thirty patients undergoing TKA under standardised anaesthesia and
      analgesia underwent an exercise (mobilisation) strategy on the first post
      operative morning consisting of 25-m walking twice, with a 20-min interval. Pain
      was assessed at rest and during passive hip and knee flexion before, and 5 and 20
      min after walk, as well as during walk. Nociceptive function (pain threshold and
      tolerance) was assessed with pressure algometry and an electrical stimulus.
      RESULTS: Pain at rest (supine) and during hip and knee flexion was significantly
      reduced 5 min (P < 0.03) and 20 min (P < 0.003) after walk compared with before
      walk, and pain was reduced during the second walk compared with the first walk (P
      < 0.034). Knee pain pressure threshold (P = 0.002) but not tolerance (P = 0.27)
      was increased following walk compared with before walk. CONCLUSION: This first
      exploratory hypothesis-generating pilot study suggests mobilisation to promote
      analgesic effects after TKA calling for future studies with a randomised,
      controlled design on exercise dose-response effects in post-surgical patients.

PMID- 22881200
TI  - Probing ring currents in Mg-porphyrins by pump-probe spectroscopy.
AB  - Theoretical studies of Manz et al. have shown that upon excitation of a Mg
      porphyrin molecule with a circularly polarized laser pulse, a ring current can be
      generated that is much stronger than what can be induced by means of an external
      magnetic field with present technology. We show that the circular dichroism
      signal of a Mg-porphyrin molecule that has been excited to a state with an inner
      ring current is proportional to the magnitude of the probability of this ring
      current and can be used for the detection of this current. In analogy to magnetic
      circular dichroism, it probes the symmetry of degenerate excited states.

PMID- 22881201
TI  - Stem cell transplantation for paediatric patients with non-anaplastic peripheral
      T-cell lymphoma in Japan.
AB  - Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in paediatric
      patients, especially results of stem cell transplantation (SCT), are relatively
      rare. We herein report the results of SCT using the Transplant Registry Unified
      Management Program system of the Japanese Society of Stem Cell Transplantation in
      paediatric patients with non-anaplastic PTCL. We analysed 26 patients (13 females
      and 13 males) aged <=18 years with non-anaplastic PTCL who underwent a total of
      28 SCT. Median age at transplantation was 13.5 years (range: 0-18 years). PTCL
      not otherwise specified was diagnosed in 17 patients; extranodal Natural Killer
      (NK)/T cell lymphoma, nasal type in nine; and subcutaneous panniculitis-like T
      cell lymphoma in two. Transplantation was with syngeneic donor in one, related
      donor in 10; unrelated donor in 10; and auto transplantation in 7. Five-year
      overall survival rate and event-free survival rate was 62.96% and 55.56%,
      respectively. Male gender, chronic graft-versus-host disease (GVHD), and reduced
      intensity conditioning were good prognostic factors in all patients. In 20
      patients with refractory or relapsed disease, male gender and chronic GVHD were
      also good prognostic factors. This study is the first report concerning
      transplantation in children with non-anaplastic PTCL, although the number of
      patients was small. Larger studies are needed to confirm these findings.

PMID- 22881202
TI  - Can telomere shortening explain sigmoidal growth curves?
AB  - A general branching process model is proposed to describe the shortening of
      telomeres in eukaryotic chromosomes. The model is flexible and incorporates many
      special cases to be found in the literature. In particular, we show how telomere
      shortening can give rise to sigmoidal growth curves, an idea first expressed by
      Portugal et al. [A computational model for telomere-dependent cell-replicative
      aging, BioSystems 91 (2008), pp. 262-267]. We also demonstrate how other types of
      growth curves arise if telomere shortening is mitigated by other cellular
      processes. We compare our results with published data sets from the biological
      literature.

PMID- 22881203
TI  - Dynamic vaccination games and variational inequalities on time-dependent sets.
AB  - This paper presents a model of a dynamic vaccination game in a population
      consisting of a collection of groups, each of which holds distinct perceptions of
      vaccinating versus non-vaccinating risks. Vaccination is regarded here as a game
      due to the fact that the payoff to each population group depends on the so-called
      perceived probability of getting infected given a certain level of the vaccine
      coverage in the population, a level that is generally obtained by the vaccinating
      decisions of other members of a population. The novelty of this model resides in
      the fact that it describes a repeated vaccination game (over a finite time
      horizon) of population groups whose sizes vary with time. In particular, the
      dynamic game is proven to have solutions using a parametric variational
      inequality approach often employed in optimization and network equilibrium
      problems. Moreover, the model does not make any assumptions upon the level of the
      vaccine coverage in the population, but rather computes this level as a final
      result. This model could then be used to compute possible vaccine coverage
      scenarios in a population, given information about its heterogeneity with respect
      to perceived vaccine risks. In support of the model, some theoretical results
      were advanced (presented in the appendix) to ensure that computation of optimal
      vaccination strategies can take place; this means, the theory states the
      existence, uniqueness and regularity (in our case piecewise continuity) of the
      solution curves representing the evolution of optimal vaccination strategies of
      each population group.

PMID- 22881204
TI  - Spatiotemporal dynamics of two generic predator-prey models.
AB  - We present the analysis of two reaction-diffusion systems modelling predator-prey
      interactions, where the predator displays the Holling type II functional
      response, and in the absence of predators, the prey growth is logistic. The local
      analysis is based on the application of qualitative theory for ordinary
      differential equations and dynamical systems, while the global well-posedness
      depends on invariant sets and differential inequalities. The key result is an
      L(infinity)-stability estimate, which depends on a polynomial growth condition
      for the kinetics. The existence of an a priori L(p)-estimate, uniform in time,
      for all p >= 1, implies L(infinity)-uniform bounds, given any nonnegative
      L(infinity)-initial data. The applicability of the L(infinity)-estimate to
      general reaction-diffusion systems is discussed, and how the continuous results
      can be mimicked in the discrete case, leading to stability estimates for a
      Galerkin finite-element method with piecewise linear continuous basis functions.
      In order to verify the biological wave phenomena of solutions, numerical results
      are presented in two-space dimensions, which have interesting ecological
      implications as they demonstrate that solutions can be 'trapped' in an invariant
      region of phase space.

PMID- 22881205
TI  - Analysis of a tuberculosis model with a case study in Uganda.
AB  - We consider a four-compartment tuberculosis model including exogenous
      reinfection. We derive sufficient conditions, in terms of the parameters of the
      system, which guarantee the occurrence of backward bifurcation. We also discuss
      the global stability of the endemic state by using a generalization of the
      Poincare-Bendixson criterion. An application is given for the case of Internally
      Displaced People's Camps in North Uganda. The study suggests how important it is
      to provide qualitative indications on the threshold value of the population
      density in the area occupied by the camps, in order to possibly eradicate the
      disease.

PMID- 22881207
TI  - The chemostat with lateral gene transfer.
AB  - We investigate the standard chemostat model when lateral gene transfer is taken
      into account. We will show that when the different genotypes have growth rate
      functions that are sufficiently close to a common growth rate function, and when
      the yields of the genotypes are sufficiently close to a common value, then the
      population evolves to a globally stable steady state, at which all genotypes
      coexist. These results can explain why the antibiotic-resistant strains persist
      in the pathogen population.

PMID- 22881206
TI  - On the Neimark-Sacker bifurcation in a discrete predator-prey system.
AB  - A two-parameter family of discrete models describing a predator-prey interaction
      is considered, which generalizes a model discussed by Murray, and originally due
      to Nicholson and Bailey, consisting of two coupled nonlinear difference
      equations. In contrast to the original case treated by Murray, where the two
      populations either die out or may display unbounded growth, the general member of
      this family displays a somewhat wider range of behaviour. In particular, the
      model has a nontrivial steady state which is stable for a certain range of
      parameter values, which is explicitly determined, and also undergoes a Neimark
      Sacker bifurcation that produces an attracting invariant curve in some areas of
      the parameter space and a repelling one in others.

PMID- 22881208
TI  - Maintenance of heterocyst patterning in a filamentous cyanobacterium.
AB  - In the absence of sufficient combined nitrogen, some filamentous cyanobacteria
      differentiate nitrogen-fixing heterocysts at approximately every 10th cell
      position. As cells between heterocysts grow and divide, this initial pattern is
      maintained by the differentiation of a single cell approximately midway between
      existing heterocysts. This paper introduces a mathematical model for the
      maintenance of the periodic pattern of heterocysts differentiated by Anabaena sp.
      strain PCC 7120 based on the current experimental knowledge of the system. The
      model equations describe a non-diffusing activator (HetR) and two inhibitors
      (PatS and HetN) that undergo diffusion in a growing one-dimensional domain. The
      inhibitors in this model have distinct diffusion rates and temporal expression
      patterns. These unique aspects of the model reflect recent experimental findings
      regarding the molecular interactions that regulate patterning in Anabaena. Output
      from the model is in good agreement with both the temporal and spatial
      characteristics of the pattern maintenance process observed experimentally.

PMID- 22881209
TI  - A spatially stochastic epidemic model with partial immunization shows in mean
      field approximation the reinfection threshold.
AB  - Recently, the notion of a reinfection threshold in epidemiological models of only
      partial immunity has been debated in the literature. We present a rigorous
      analysis of a model of reinfection which shows a clear threshold behaviour at the
      parameter point where the reinfection threshold was originally described.
      Furthermore, we demonstrate that this threshold is the mean field version of a
      transition in corresponding spatial models of immunization. The reinfection
      threshold corresponds to the transition between annular growth of an epidemics
      spreading into a susceptible area leaving recovered behind and compact growth of
      a susceptible-infected-susceptible region growing into a susceptible area. This
      transition between annular growth and compact growth was described in the physics
      literature long before the reinfection threshold debate broke out in the
      theoretical biology literature.

PMID- 22881212
TI  - The heritability of delusional-like experiences.
AB  - OBJECTIVE: Delusional-like experiences (DLE) are common in the general community
      and are associated with a family history of mental illness. The aim of this study
      was to estimate the heritability of DLE. METHOD: The Peter's Delusional Inventory
      (PDI) was administered to a population-based cohort of mothers (n = 2861, aged 35
      67 years) and their adult offspring (n = 3079, aged 18-23 years). Heritability of
      DLE was estimated from the sum scores of the 21 item PDI under the assumption
      that the covariance between mother-offspring scores is attributable to shared
      additive genetic factors. RESULTS: The means (medians and standard deviations)
      for the total PDI scores for the mothers and their offspring were 3.6 (3.0, 3.0)
      and 5.0 (4.0, 3.5), respectively. The Pearson correlation coefficient between
      mother and offspring PDI scores was 0.17 (P < 0.001). The heritability was
      estimated to be 0.35 (standard error 0.04). CONCLUSION: Heritable factors
      contribute to over a third of the variance of PDI scores in this population. In
      light of the association between a family history of a wide range of mental
      disorders and DLE, these experiences may represent a useful quantitative
      endophenotype for genetic studies of common mental disorders in population
      settings.

PMID- 22881213
TI  - Histochemical identification of sialylated glycans in Xenopus laevis testis.
AB  - Carbohydrate chains of glycoprotein and glycosphingolipids are highly diverse
      molecules involved in many cell functions, including cell recognition, adhesion
      and signalling. Sialylated glycans are of special interest because the terminal
      position of sialic acid (NeuAc) in glycans linked by different ways to
      subterminal monosaccharides has been shown to be involved in several biological
      processes, as occurs with gangliosides, which have been reported as being
      essential in spermatogenesis in mammals. Some glycan-binding proteins, the
      lectins, which specifically recognize glycan sequences, have been extensively
      used to characterize tissue and cell carbohydrates by means of cytochemical
      techniques. The aim of the present work was to determine the presence of NeuAc by
      means of histochemical techniques in the testis of Xenopus laevis, an animal
      model widely used in cell and molecular biology research. However, considering
      that some NeuAc-binding lectins are capable of binding to N-acetylglucosamine
      (GlcNAc), other GlcNAc-binding lectins were also assayed. The results showed that
      NeuAc is mainly expressed in the interstitium, and only a weak labelling in the
      male germ cells was observed. Most NeuAc was located in O-linked
      oligosaccharides, but some masked NeuAc in N-glycans were identified in primary
      and secondary spermatogonia and spermatocytes. By contrast, GlcNAc was widely
      expressed in all germ cell types. Deglycosylative pre-treatments suggest that
      both N- and O-glycans and/or glycolipids could be responsible for this labelling.
      In addition, GlcNAc in O-linked oligosaccharides has been identified in
      spermatogonial cells. The acrosome of spermatids was always negative. Variations
      of glycan expression have been found in different cell types, suggesting that
      glycosylation is modified during spermatogenetic development.

PMID- 22881214
TI  - Synthetic applications and inversion dynamics of configurationally stable 2
      lithio-2-arylpyrrolidines and -piperidines.
AB  - In diethyl ether, N-Boc-2-lithio-2-arylpiperidines have been found to be
      configurationally stable at -80  degrees C, whereas N-Boc-2-lithio-2
      arylpyrrolidines are configurationally stable at -60  degrees C. Several tertiary
      benzylic carbanions derived from enantioenriched 2-aryl heterocycles have been
      successfully alkylated or acylated with little to no loss of enantiopurity. The
      scope of the reactions has been explored. The enantiomerization dynamics of N-Boc
      2-lithio-2-phenylpyrrolidine and N-Boc-2-lithio-2-phenylpiperidine have been
      studied in the presence of different solvents and achiral ligands.

PMID- 22881215
TI  - A clinical evaluation of four non-Luer spinal needle and syringe systems.
AB  - We performed an evaluation of non-Luer spinal devices supplied by four
      manufacturers or suppliers: Polymedic; Pajunk; Sarstedt; and Smiths. For each
      supplier, 100 evaluations were performed using a 25-G 90-mm spinal needle, 3-ml
      syringe, 5-ml syringe and filter needle; for comparison, 100 evaluations were
      performed with our standard Luer equipment. The non-Luer devices were associated
      with more qualitative problems compared with the Luer devices, for example, poor
      feel of dural puncture (9-32% vs 10%, respectively), poor observation of
      cerebrospinal fluid in the hub (3-27% vs 0%), and connection problem of the
      syringe to the spinal needle (7-33% vs 0%). There was also more frequent failure
      to achieve the spinal injection due to equipment-related causes (4-7% vs 0%,
      respectively). Median (IQR [range]) numeric satisfaction scores for the spinal
      needles were: Luer 10 (9-10 [7-10]); Polymedic 7 (4-8 [0-10]; Pajunk 7 (5-8 [0
      10]); Sarstedt 7 (6-8 [0-10]); and Smiths 9 (7-10 [0-10]) (p<0.0001).
      Satisfaction scores for all spinal equipment were: Luer 10 (9-10 [5-10]);
      Polymedic 8 (6-8 [0-10]); Pajunk 7 (5-7 [1-9]); Sarstedt 8 (6-8 [0-10]); and
      Smiths 8 (8-9 [2-10]) (p<0.0001). Between 21% and 75% of non-Luer evaluations
      were rated with satisfaction worse than the usual Luer needle compared with 0-10%
      rated better, depending on the needle type. Between 22% and 76% of non-Luer
      evaluations were rated with satisfaction worse than the usual Luer equipment
      compared with 0-14% rated better. Specific concerns included poor feel of tissue
      planes and observation of cerebrospinal fluid (Polymedic), difficulty with
      connection of the syringe to the spinal needle and trocar removal (Pajunk), poor
      feel of tissue planes and needle flexibility (Sarstedt) and difficulty with
      connection of the syringe to the spinal needle (Smiths). We could not demonstrate
      a short-term learning curve for the new devices. Decisions on purchasing and
      implementation of the new non-Luer equipment will have to acknowledge that
      clinicians may have greater technical problems and reduced satisfaction compared
      with the current equipment.

PMID- 22881216
TI  - Photothermally reduced graphene as high-power anodes for lithium-ion batteries.
AB  - Conventional graphitic anodes in lithium-ion batteries cannot provide high-power
      densities due to slow diffusivity of lithium ions in the bulk electrode material.
      Here we report photoflash and laser-reduced free-standing graphene paper as high
      rate capable anodes for lithium-ion batteries. Photothermal reduction of graphene
      oxide yields an expanded structure with micrometer-scale pores, cracks, and
      intersheet voids. This open-pore structure enables access to the underlying
      sheets of graphene for lithium ions and facilitates efficient intercalation
      kinetics even at ultrafast charge/discharge rates of >100 C. Importantly,
      photothermally reduced graphene anodes are structurally robust and display
      outstanding stability and cycling ability. At charge/discharge rates of ~40 C,
      photoreduced graphene anodes delivered a steady capacity of ~156 mAh/g(anode)
      continuously over 1000 charge/discharge cycles, providing a stable power density
      of ~10 kW/kg(anode). Such electrodes are envisioned to be mass scalable with
      relatively simple and low-cost fabrication procedures, thereby providing a clear
      pathway toward commercialization.

PMID- 22881217
TI  - Photoacoustic analyzer for the artifact-free parallel detection of soot and NO2
      in engine exhaust.
AB  - Soot particles and NO(2) are among the most hazardous emissions from diesel
      combustion engines. Currently, no analytical system exists which allows for the
      simultaneous, time-resolved online analysis of these two components. Furthermore,
      state-of-the-art NO(2) analyzers for exhaust gas require particle filtration
      prior to the analysis, which may induce artifacts and measurement errors. We
      present a photoacoustic instrument which overcomes these drawbacks. The
      sensitivity of the instrument (LOD(NO(2)) = 0.3 ppm, LOD(soot) = 0.54 MUg m(-3),
      limit of detection/quantification) as well as the temporal resolutions are
      dictated by the needs of typical automotive applications. Also required for this
      specific application, we developed PA cells which can be heated to 80  degrees C,
      while the microphones maintain a temperature of 45  degrees C. Setup and specific
      parameters of the instrument are discussed, and the results of typical engine
      tests are compared to reference analytical instrumentation.

PMID- 22881218
TI  - A death following hemopericardium due to rupture of a right ventricular aneurysm
      due to a congenital ventricular septal defect.
AB  - Right ventricular aneurysm (RVA) is a rare clinicopathological entity. Although
      it occurs as a consequence of a variety of conditions, congenital ventricular
      septal defect (VSD) as an etiology for the RVA has not been previously reported.
      A 42-year-old man without a significant family or past medical history was found
      dead in bed. At autopsy, the internal examination revealed a hemopericardium of
      280 mL. There was a 1.5 cm diameter ruptured aneurysm of the free wall of the
      right ventricle. A VSD was present in the lower part of the muscular
      interventricular septum. The RVA was directly facing to the VSD without any
      obstruction in between. Microscopically the wall of the aneurysm consisted only
      of a thin layer of fibrous tissue transmurally with minimal interspersed
      cardiomyocytes. Cause of death was concluded as hemopericardium following rupture
      of RVA caused by a congenital VSD.

PMID- 22881219
TI  - Prevalence and predictors of drooling in 7- to 14-year-old children with cerebral
      palsy: a population study.
AB  - AIM: To establish a prevalence estimate for drooling and explore factors
      associated with drooling in a population sample of children with cerebral palsy
      (CP) aged 7 to 14 years living in Victoria, Australia. METHOD: A self-report
      questionnaire was used to collect data on drooling from parents of children born
      between 1996 and 2001, and registered with the Victorian Cerebral Palsy Register.
      RESULTS: A total of 385 children (231 males, 154 females; mean age 10y 9mo [SD 1y
      7mo], range 8-14y) were studied. The clinical type and distribution of CP were
      spastic (341), ataxic (16), dyskinetic (17), hypotonic (10), and unknown (1).
      Distribution in Gross Motor Function Classification System (GMFCS) levels was I
      (103), II (98), III (52), IV (63), V (61), and unknown (8). After adjustment for
      topographical pattern of motor impairment and GMFCS level, 40% were reported to
      have experienced drooling between 4 years of age and the time of completing the
      questionnaire. A significantly higher prevalence of drooling was found in
      children with poor gross motor function and in those with more severe
      presentations of CP, including poor head control, difficulty with eating, and
      inability to sustain lip closure (p<0.001 for each). Drooling was shown to be
      significantly associated with both intellectual disability and epilepsy in this
      group of children (p<0.001 for both). INTERPRETATION: With a prevalence of 40%,
      drooling is an important comorbidity in CP. It was considered severe in 15% of
      children. Poor oromotor function was associated with drooling and could be the
      target of interventions for this under-researched problem.

PMID- 22881220
TI  - Assessing induced folding within the intrinsically disordered C-terminal domain
      of the Henipavirus nucleoproteins by site-directed spin labeling EPR
      spectroscopy.
AB  - This work aims at characterizing structural transitions within the intrinsically
      disordered C-terminal domain of the nucleoprotein (NTAIL) from the Nipah and
      Hendra viruses, two recently emerged pathogens gathered within the Henipavirus
      genus. To this end, we used site-directed spin labeling combined with electron
      paramagnetic resonance spectroscopy to investigate the alpha-helical-induced
      folding that Henipavirus NTAIL domains undergo in the presence of the C-terminal
      X domain of the phosphoprotein (PXD). For each NTAIL protein, six positions
      located within four previously proposed molecular recognition elements (MoREs)
      were targeted for spin labeling, with three of these positions (475, 481, and
      487) falling within the MoRE responsible for binding to PXD (Box3). A detailed
      analysis of the impact of the partner protein on the labeled NTAIL variants
      revealed a dramatic modification in the environment of the spin labels grafted
      within Box3, with the observed modifications supporting the formation of an
      induced alpha-helix within this region. In the free state, the slightly lower
      mobility of the spin labels grafted within Box3 as compared to the other
      positions suggests the existence of a transiently populated alpha-helix, as
      already reported for measles virus (MeV) NTAIL. Comparison with the well
      characterized MeV NTAIL-PXD system, allowed us to validate the structural models
      of Henipavirus NTAIL-PXD complexes that we previously proposed. In addition, this
      study highlighted a few notable differences between the Nipah and Hendra viruses.
      In particular, the observation of composite spectra for the free form of the
      Nipah virus NTAIL variants spin labeled in Box3 supports conformational
      heterogeneity of this partly pre-configured alpha-helix, with the pre-existence
      of stable alpha-helical segments. Altogether these results provide insights into
      the molecular mechanisms of the Henipavirus NTAIL-PXD binding reaction.

PMID- 22881221
TI  - Atmospheric pressure laser-induced acoustic desorption chemical ionization mass
      spectrometry for analysis of saturated hydrocarbons.
AB  - We present atmospheric pressure laser-induced acoustic desorption chemical
      ionization (AP/LIAD-CI) with O(2) carrier/reagent gas as a powerful new approach
      for the analysis of saturated hydrocarbon mixtures. Nonthermal sample
      vaporization with subsequent chemical ionization generates abundant ion signals
      for straight-chain, branched, and cycloalkanes with minimal or no fragmentation.
      [M - H](+) is the dominant species for straight-chain and branched alkanes. For
      cycloalkanes, M(+*) species dominate the mass spectrum at lower capillary
      temperature (<100  degrees C) and [M - H](+) at higher temperature (>200  degrees
      C). The mass spectrum for a straight-chain alkane mixture (C(21)-C(40)) shows
      comparable ionization efficiency for all components. AP/LIAD-CI produces
      molecular weight distributions similar to those for gel permeation chromatography
      for polyethylene polymers, Polywax 500 and Polywax 655. Coupling of the technique
      to Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) for the
      analysis of complex hydrocarbon mixtures provides unparalleled mass resolution
      and accuracy to facilitate unambiguous elemental composition assignments, e.g.,
      1754 peaks (rms error = 175 ppb) corresponding to a paraffin series (C(12)-C(49),
      double-bond equivalents, DBE = 0) and higher DBE series corresponding to
      cycloparaffins containing one to eight rings. Isoabundance-contoured plots of DBE
      versus carbon number highlight steranes (DBE = 4) of carbon number C(27)-C(30)
      and hopanes of C(29)-C(35) (DBE = 5), with sterane-to-hopane ratio in good
      agreement with field ionization (FI) mass spectrometry analysis, but performed at
      atmospheric pressure. The overall speciation of nonpolar, aliphatic hydrocarbon
      base oil species offers a promising diagnostic probe to characterize crude oil
      and its products.

PMID- 22881222
TI  - Individual variation in sleep-wake rhythms in free-living birds.
AB  - Ultradian rhythms, such as sleep-wake periodicities, during the night might
      represent basic rest-activity cycles of organisms that are fundamental to the
      temporal organization and synchronization of behavior throughout the day.
      However, in contrast to circadian rhythms, little is known about the underlying
      oscillators and molecular mechanisms of higher-frequency rhythms. A fundamental
      step for the understanding of the mechanisms of these latter periodicities is the
      analysis of variation in sleep-wake cycles in free-living animals, which can help
      in estimating the relative importance of genetic and environmental influence on
      the rhythmicity. We analyzed variation in the level of rhythmicity and period
      length (tau) of behaviorally defined sleep-wake cycles in a natural population of
      blue tits Cyanistes caeruleus. Our results indicate that the expression of
      periodicity in sleep-wake patterns, but not tau, has a strong individual-specific
      basis. The within-individual repeatability estimate of the expression of
      periodicity was .45 (95% confidence interval: .35-.55) when data from males and
      females were combined. In addition, periodicity was influenced by specific
      environmental factors, such as night temperature, seasonal date, and age of the
      individual. Most strikingly, low nighttime temperature negatively affected
      periodicity of sleep-wake patterns, potentially via a hypothermic response of the
      birds. Our results further suggest that tau is influenced by photoperiod. Blue
      tits showed longer sleep-wake rhythms when the nights were longer. These
      observations suggest a genetic basis for the incidence of rhythmic sleep-wake
      behavior in addition to environmental modifications of their specific expression.

PMID- 22881223
TI  - Modulation of baroreflex function by rosiglitazone in prediabetic hyperglycemic
      rats.
AB  - Baroreflex sensitivity (BRS) is abnormal in the prediabetic state. This study was
      conducted to determine effects of chronic rosiglitazone (RSG), an insulin
      sensitizer, on BRS in prediabetic hyperglycemic (PDH) rats induced by
      nicotinamide and streptozotocin. The fasting and postprandial blood glucose
      levels were 5.6-6.9 and 7.8-11.0 mmol/l, respectively. Rats were treated with RSG
      or saline for 12 weeks. BRS response to phenylephrine (PE-BRS) or sodium
      nitroprusside (NP-BRS) was determined by linear regression method. Cardiac
      sympathetic and parasympathetic influences were determined by autonomic
      blockades. In the saline-treated PDH rats, PE-BRS was enhanced early at week 4
      and became greater at week 12. Abnormalities in NP-BRS and cardiac autonomic
      influences were found only after week 12. Four weeks of RSG treatment normalized
      blood glucose levels but not PE-BRS. All altered cardiovascular variables were
      completely restored by 12 weeks of RSG treatment. The correlation between BRS and
      blood glucose levels in saline-treated PDH rats was significant at week 12, but
      no correlation was found in RSG-treated rats. In conclusion, hyperglycemia, even
      in the prediabetic state, may play a role in BRS abnormalities. RSG treatment
      early in the prediabetic state may normalize BRS via cardiac autonomic
      modulation, besides its anti-hyperglycemic action.

PMID- 22881224
TI  - Age-associated changes in Ca(2+)-ATPase and oxidative damage in sarcoplasmic
      reticulum of rat heart.
AB  - Altered Ca(2+) handling may be responsible for the development of cardiac
      contractile dysfunctions with advanced age. In the present study, we investigated
      the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of
      Ca(2+)-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of
      cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month
      old Wistar rats. Although activity of Ca(2+)-ATPase decreased with advancing age,
      no differences in relative amounts of SERCA 2a and phospholamban protein were
      observed. On the other hand, significant accumulation of protein oxidative damage
      occurred with aging. The results of this study suggest that age-related
      alteration in Ca(2+)-ATPase activity in the rat heart is not a consequence of
      decreased protein levels of SERCA 2a and phospholamban, but could arise from
      oxidative modifications of SR proteins. Cellular oxidative damage caused by
      reactive oxygen species could contribute to age-related alternations in
      myocardial relaxation.

PMID- 22881225
TI  - Time-lapse cleavage rating predicts human embryo viability.
AB  - Chronology of three consecutive mitotic events in human pre-implantation embryos
      was examined by time-lapse imaging. In zygotes producing well-formed and
      pregnancy-yielding expanded blastocysts, uniform time-patterning of cleavage
      clusters (c) and interphases (i) was revealed: i2=11+/-1, i3=15+/-1, i4=23+/-1 h
      / c2=15+/-5, c3=40+/-10, c4=55+/-15 min. Oppositely, shortened or prolonged
      durations of one or more cell cycles were strongly predictive of poor
      implantation and development. Furthermore, trichotomic mitosis was discovered in
      17 % of cases - zygotes cleaved into 3 blastomeres and 2-cell embryos into 5-6
      cells (instead of normal 2 and 4). During conventional clinical assessment, such
      embryos are indistinguishable from normal, often considered just-in-course of the
      next cell cycle. Only detailed time-lapse monitoring paced at 10-minute intervals
      had proven all these embryos to be absolutely unviable, even in rare cases when
      they reduced their hypercellularity to normal cell counts via cell-cell fusion.
      Overall, we demonstrate that time-lapse embryo cleavage rating (ECR) as a
      standalone diagnostic procedure allows for effective identification of viable
      early embryos with 90 % specificity, while elimination of good-looking but
      unviable embryos can be assumed with a specificity of 100 %. Thus, making this
      non-invasive and contactless approach worth of addition to routine embryo
      screening in clinical IVF programs.

PMID- 22881226
TI  - Genetic strain-dependent protein metabolism and muscle hypertrophy under chronic
      isometric training in rat gastrocnemius muscle.
AB  - Genetic strain-dependent reactivity to mechanical stimuli in rat skeletal muscle
      has not been examined. This study aimed to examine whether genetic strain
      dependency is associated with reactivity in protein metabolism and the resultant
      muscle hypertrophy after isometric resistance training (RT). The right triceps of
      Sprague-Dawley (SD) and Wistar rats underwent 12 sessions of RT. After RT, a
      transition from the IIb to the IIx myosin heavy-chain isoform was observed in
      both strains. In SD rats, the lateral gastrocnemius muscle (LG) mass of the
      trained legs (TRN) was significantly higher than that of the control legs (CON)
      (7.8 %, P<0.05). Meanwhile, in Wistar rats, the LG mass was unchanged. In SD
      rats, the levels of 70-kDa ribosomal protein S6 kinase (p70S6k) and forkhead box
      3a (FOXO3a) phosphorylation in the TRN were significantly greater than those of
      the CON (2.2- and 1.9-fold, respectively; P<0.05). The expression of muscle ring
      finger-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) in the TRN were
      significantly lower than those of the CON (0.6- and 0.7-fold, respectively;
      P<0.05). However, in Wistar rats, there was no significant difference. These
      results suggest a genetic strain difference in protein metabolism. This
      phenomenon may be useful for studying individual differences in response to RT.

PMID- 22881227
TI  - Nicotine and kainic acid effects on cortical epileptic afterdischarges in
      immature rats.
AB  - Aim of the study was to test the effect of nicotine (NIC) and kainic acid (KA) co
      treatment in immature rats. Male Wistar albino rats (two different age groups)
      were chosen for the study. Experiments started on postnatal day (PD) 8 or 21 and
      animals were treated twice a day for three days with nicotine, fourth day KA was
      administered. Animals at PD12 (PD25 respectively) were examined
      electrophysiologically for cortical epileptic afterdischarges (ADs). First
      cortical ADs in PD12 animals were longer, when compared to PD25 rats (group
      treated with both substances). Nor NIC or KA treatment affected the length of
      discharges in PD12 rats. Older experimental group exhibited the shortening of the
      first ADs (group treated with NIC and KA, compared with groups exposed to single
      treatment). Few changes were found in KA treated group - 2(nd) and 4(th) ADs were
      shorter when compared with first ADs. These results demonstrate that NIC
      treatment played minor role in seizure susceptibility of PD12 rats, sensitivity
      to NIC differs during ontogenesis and subconvulsive dose of KA influenced the
      length of discharges only in PD25 animals.

PMID- 22881228
TI  - Immunohistochemical demonstration of blood vessels alpha-actin down-regulation in
      LPS-treated pregnant mice.
AB  - Lipopolysaccharide (LPS), produced by gram-negative bacteria, mediates
      vasodilatation, changing the action of contractile smooth muscle by increasing
      expression of nitric oxide synthase and prostaglandin. For the first time we
      demonstrate, by immunohistochemical methods, that administration of LPS to
      pregnant mice causes alpha-actin-mediated down-regulation of contractile
      filaments in uterine blood vessels, thereby potentially increasing vessels
      permeability, blood supply, and immune cells homing to this environment,
      culminating in the reestablishment of uterine homeostasis.

PMID- 22881229
TI  - Monitoring of the course of sepsis in hematooncological patients by
      extrapituitary prolactin expression in peripheral blood monocytes.
AB  - Our study explored the role of extrapituitary prolactin (PRL) and toll-like
      receptors (TLR)2 and TLR4 in defense reaction of immune system to bacterial
      infection. Forty-two patients diagnosed with sepsis were recruited and blood
      samples were withdrawn after patients' admission to hospital, after the end of
      acute phase of sepsis and after the sepsis has been resolved, respectively.
      Seventeen patients died of sepsis; thus, only one sample collected just before
      death could be processed. PRL and TLR2/4 mRNA levels were measured in CD14+ blood
      monocytes by QPCR and PRL -1149 G/T SNP genotyped. The TLRs mRNA expression was
      markedly elevated in all patients groups in comparison to healthy controls mRNA
      levels; the highest upregulation of monocytic TLR2 in sepsis (16.4 times,
      P<0.0001) was detected in patients who did not survive septic complications. PRL
      mRNA expression in monocytes from non-survivors tended to be lower (4.5 fold
      decrease, P=NS) compared to control levels and it was 6.2 times reduced compared
      to PRL mRNA expression in second blood sample from survivors (P<0.05). The PRL 
      1149 G/T SNP had no effect on PRL mRNA response during sepsis. Our data suggest
      that increased prolactin mRNA expression in monocytes is associated with better
      outcome and improved survival rate in sepsis with no apparent effect of PRL -1149
      G/T SNP on monocytic prolactin response.

PMID- 22881230
TI  - Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis.
AB  - Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new
      adipokine. The aim of this study was to assess FGF-21 levels in patients with
      rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship
      between FGF-21, disease activity and metabolic status. The levels of FGF-21 in
      serum and synovial fluid samples from 38 patients with RA and 42 control
      individuals with OA were determined by ELISA. Patients were assessed for disease
      activity using the disease activity score (DAS28), a serum glucose and lipid
      profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and
      synovial fluid (p=0.010) samples were significantly higher in patients with RA
      when compared with OA. The levels of FGF-21 in the serum significantly correlated
      with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels
      adjusted for confounders correlated positively with C-reactive protein. The
      levels of FGF-21 were positively correlated with BMI in patients with RA;
      however, the levels were not associated with disease activity or lipid profiles.
      Furthermore, serum FGF-21 levels were significantly higher in seropositive
      compared with seronegative RA patients. This work shows that patients with
      seropositive RA have increased levels of FGF-21. The results suggest that FGF-21
      is related to BMI but not disease activity or lipid profiles in patients with RA.

PMID- 22881231
TI  - Circulatory and adipose tissue leptin and adiponectin in relationship to resting
      energy expenditure in patients with chronic obstructive pulmonary disease.
AB  - Increases in resting energy expenditure (REE) likely contribute to weight loss in
      various chronic diseases. In chronic obstructive pulmonary disease (COPD),
      relationships between the ventilatory impairment and increased REE, and between
      disturbances in adipokines and weight loss were previously described. Therefore,
      we investigated serum levels and adipose tissue expression of leptin and
      adiponectin, and their relationships to REE in patients with COPD. In 44 patients
      with stable COPD (38 male; age 62.3+/-7.2 years), REE was assessed using indirect
      calorimetry. Subcutaneous adipose tissue samples were analyzed using real-time
      PCR. From underweight [n=9; body mass index (BMI) <20.0 kg.m(-2)], to normal
      weight-overweight (n=24, BMI=20.0-29.9 kg.m(-2)) and obese patients (n=11;
      BMI>/=30 kg.m(-2)), REE adjusted for body weight decreased (32.9+/-6.1 vs. 26.2+/
      5.8 vs. 23.9+/-6.6 kcal.kg(-1).24 h(-1), p=0.006), serum levels and adipose
      tissue expression of leptin increased (p<0.001 for both), and serum and adipose
      tissue adiponectin decreased (p<0.001; p=0.004, respectively). REE was inversely
      related to serum and adipose tissue leptin (R=-0.547, p<0.001; R=-0.458,
      p=0.002), and directly to serum adiponectin (R=0.316, p=0.039). Underweight
      patients had increased REE compared to normal weight-overweight patients, in
      association with reductions in serum and adipose tissue leptin, and increased
      serum adiponectin, suggesting a role of adipokines in energy imbalance in COPD
      related cachexia.

PMID- 22881232
TI  - Peripheral arterial stiffness in primary aldosteronism.
AB  - Aldosterone overproduction increases arterial wall stiffness by accumulation of
      different types of collagen fibres and growth factors. Our previous studies
      showed that central (aortic) arterial stiffness is increased in primary
      aldosteronism (PA) independently of concomitant hypertension and that these
      changes might be reversible after successful adrenalectomy. There is limited data
      available on the potential impact of mineralocorticoid overproduction on the
      deterioration of peripheral arterial stiffness. The current study was thus aimed
      at investigating the effect of aldosterone overproduction on peripheral arterial
      stiffness assessed by peripheral (femoral-ankle) pulse wave velocity (PWV) in PA
      patients compared with essential hypertension (EH) patients. Forty-nine patients
      with confirmed PA and 49 patients with EH were matched for age, blood pressure,
      body mass index, lipid profile, and fasting glucose. PWV was obtained using the
      Sphygmocor applanation tonometer. Both peripheral and central PWV were
      significantly higher in PA patients compared to EH patients, while clinical blood
      pressures were similar. Plasma aldosterone level was the main predictor of
      peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not
      preferentially affect central arterial system. Fibroproliferative effect of
      higher aldosterone levels lead to alteration of central-elastic as well as
      peripheral-muscular arteries with subsequent increase in its stiffness.

PMID- 22881233
TI  - Thyroid hormone abnormalities in hemodialyzed patients: low triiodothyronine as
      well as high reverse triiodothyronine are associated with increased mortality.
AB  - Numerous abnormalities of thyroid hormones in end-stage renal disease (ESRD) have
      been described. Our aim was to analyze the impact of these abnormalities on
      survival. In 167 hemodialyzed ESRD patients, TSH and thyroid hormone levels (T4,
      fT4, T3, fT3, rT3) were determined. The patients were then prospectively followed
      up for up to 5 years and the possible impact of any observed abnormalities on
      their mortality was studied. Only 16.8 % patients had all six tests within the
      reference range. The pattern of nonthyroidal illness syndrome was found in 56.3
      %. Low T3 was particularly common (44.3 %), and clearly associated with increased
      6- and 12-month mortality and decreased overall survival (log rank test,
      P=0.007). Independent of T3 levels (Spearman correlation, NS), increased rT3 was
      more frequently observed (9.9 %) than expected from the literature, and was also
      related to increased mortality and decreased survival (log rank test, P=0.021).
      Increased rT3 may be more common in ESRD patients than previously described, and
      together with decreased T3 it may serve as an indicator of poor prognosis in
      subsequent months.

PMID- 22881234
TI  - Curcumin provides incomplete protection of the kidney in ischemia reperfusion
      injury.
AB  - Curcumin, a component of the spice turmeric, was shown to have a protective
      effect on acute kidney injury markers following ischemia-reperfusion injury
      (IRI). However, its effect on glomerular and tubular renal functions following
      IRI is not known and this data is probably of more clinical relevance. In this
      study, curcumin was tested for its effect on renal functional parameters
      following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C
      30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45
      (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin
      (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery
      blood flow was measured by a flowmeter before and 15 minutes after reperfusion.
      Serum TNF-alpha was measured before and 2 days after ischemia. The function of
      both kidneys was measured 2 days following ischemia using clearance technique.
      IRI caused significant increase in TNF-alpha in all groups. Curcumin
      significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and
      associated histological changes but did not affect the alterations in renal
      artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or
      tubular (urinary volume, urinary sodium and fractional excretion of sodium)
      functions following 30 or 45 min of IRI.

PMID- 22881235
TI  - Oral transmucosal delivery of domperidone from immediate release films produced
      via hot-melt extrusion technology.
AB  - The objective of the study was to prepare and characterize the domperidone (DOM)
      hot-melt extruded (HME) buccal films by both in vitro and in vivo techniques. The
      HME film formulations contained PEO N10 and/or its combination with HPMC E5 LV or
      Eudragit RL100 as polymeric carriers, and PEG3350 as a plasticizer. The blends
      were co-processed at a screw speed of 50 rpm with the barrel temperatures ranging
      from 120-160 degrees C utilizing a bench top co-rotating twin-screw hot-melt
      extruder using a transverse-slit die. The HME films were evaluated for drug
      content, drug excipient interaction, in vitro drug release, mechanical
      properties, in vivo residence time, in vitro bioadhesion, swelling and erosion,
      ex vivo permeation from HME films and the selected optimal formulation was
      subjected for bioavailability studies in healthy human volunteers. The extruded
      films demonstrated no drug excipient interaction and excellent content
      uniformity. The selected HME film formulation (DOM2) exhibited a tensile strength
      (0.72 Kg/mm(2)), elongation at break (28.4% mm(2)), in vivo residence time (120
      min), peak detachment force (1.55 N), work of adhesion (1.49 mJ), swelling index
      (210.2%), erosion (10.5%) and in vitro drug release of 84.8% in 2 h.
      Bioavailability from the optimized HME buccal films was 1.5 times higher than the
      oral dosage form and the results showed statistically significant (p < 0.05)
      difference. The ex vivo-in vivo correlation was found to have biphasic pattern
      and followed type A correlation. The results indicate that HME is a viable
      technique for the preparation of DOM buccal-adhesive films with improved
      bioavailability characteristics.

PMID- 22881236
TI  - Added versus accumulated sugars on color development and acrylamide formation in
      french-fried potato strips.
AB  - Added (glucose addition) versus accumulated (in situ sugar development via cold
      temperature storage) sugar treatments were investigated in relation to acrylamide
      formation within fried potato strips at standardized levels of finish-fried color
      (Agtron color scores ranged from 36 to 84). The added sugar treatment exhibited a
      relatively reduced rate of acrylamide formation and generally possessed a lower
      and less variable acrylamide content (61-1290 ng/g) than the accumulated sugar
      scheme (61-2191 ng/g). In a subsequent experiment, added fructose applied to
      strip surfaces via dipping prior to frying favored acrylamide formation over
      color development relative to added glucose, for which the reverse trend was
      observed. Thus, where acrylamide differences were noted between added and
      accumulated sugar treatments (given equivalent Agtron color scores), this result
      was likely aided by the relative higher fructose content in strips of the
      accumulated sugar scheme rather than simply a greater relative concentration of
      total reducing sugars.

PMID- 22881237
TI  - The future role of monoclonal antibody therapy in childhood acute leukaemias.
AB  - Leukaemia is the single most common childhood malignancy. With modern treatment
      regimens, survival in acute lymphoblastic leukaemia (ALL) approaches 90%. Only
      about 70% of children with acute myeloid leukaemia (AML) achieve long term
      survival. Patients who relapse have a dismal prognosis. Novel therapeutic
      approaches are needed to improve treatment outcomes in newly-diagnosed patients
      with a poor prognosis and for patients with relapsed/refractory disease that have
      limited treatment options. One promising approach in treating haematological
      malignancies has been the use of monoclonal antibodies to target cell surface
      antigens expressed on malignant cells. Most success with monoclonal antibody
      therapy in the treatment of haematological malignancies has come in the setting
      of adult B-cell non-Hodgkin lymphoma with the addition of the anti-CD20
      monoclonal antibody rituximab to standard treatment regimens. In order to further
      advance treatment of haematological malignancies, novel monoclonal antibodies
      continue to be developed that target a variety of cell surface antigens. Several
      antibodies continue to be investigated in childhood leukaemias. This review will
      discuss the development of monoclonal antibodies that target a variety of cell
      surface antigens for the treatment of childhood ALL and the use of the anti-CD33
      antibody gemtuzumab ozogamicin in the treatment of childhood AML.

PMID- 22881238
TI  - Attentional bias toward personally relevant health-threat words.
AB  - Conflicting findings have emerged regarding the presence of attentional biases
      (ABs) in health anxiety, probably due to methodological limitations in the
      stimuli used in cognitive tasks and the assessment of health anxiety-relevant
      factors. The current study sought to examine ABs toward health-related threats
      using idiographically chosen health-threat words in a non-clinical sample. A
      modified dot-probe task using idiographically selected health-threat words was
      administered to an undergraduate sample. Self-report measures were administered
      to assess somatic, cognitive, and behavioral aspects of health anxiety, in
      addition to assessing negative affect, anxiety sensitivity, and experience of
      actual medical conditions. Results showed that behavioral and somatic aspects of
      health anxiety were significantly associated with AB toward personally relevant
      threat words, even after controlling for negative affect, anxiety sensitivity,
      and experience of actual medical conditions. Additional analyses revealed that
      these biases reflected difficulty disengaging attention from threat rather than a
      facilitated detection of threat. In contrast, illness-related cognitions were
      found to be unrelated to ABs. These findings suggest an association between
      threat-related ABs and excessive health-care seeking efforts. 

PMID- 22881275
TI  - High resolution imaging of neuronal connectivity.
AB  - Connectomics is an emerging field that aims to generate and analyse neuronal
      connectivity data with high-throughput to gain knowledge about the brain. The
      realization of this goal largely depends on the development of innovative
      microscopy techniques that can produce large-scale three-dimensional images of
      brain tissue at nanoscale resolution and automated analysis tools that can
      extract relevant information from these images. This review surveys the
      challenges associated with generating the images needed for neuronal connectivity
      maps and how these challenges may be overcome by novel optical methods that allow
      sub-diffraction-limit imaging.

PMID- 22881276
TI  - Embryonic development of the skull of the Andean lizard Ptychoglossus bicolor
      (Squamata, Gymnophthalmidae).
AB  - The study of cranial design and development in Gymnophthalmidae is important to
      understand the ontogenetic processes behind the morphological diversity of the
      group and to examine the possible effects of microhabitat use and other
      ecological parameters, as well as phylogenetic constraints, on skull anatomy.
      Complete morphological descriptions of embryonic skull development within
      Gymnophthalmidae are non-existent. Likewise, very little is known about the
      complete chondrocranium of the family. Herein, the development of the skull of
      the semi-fossorial lizard Ptychoglossus bicolor is described along with an
      examination of the chondrocranium of other gymnophthalmid taxa and the teiid
      Cnemidophorus lemniscatus. Cranial chondrification begins with early
      condensations in the ethmoid, orbitotemporal and occipital regions of the
      chondrocranium as well as the viscerocranium. Ossification of the skull starts
      with elements of the dermatocranium (pterygoid, prefrontal, maxilla and jugal).
      The orbitosphenoid is the last chondral bone to appear. At birth, the skull is
      almost completely ossified and exhibits a large frontoparietal fontanelle. In
      general terms, the chondrocranium of the gymnophthalmids studied is
      characteristic of lacertiform terrestrial lizards, in spite of their life habits,
      and resembles the chondrocranium of C. lemniscatus in many aspects. However, the
      gymnophthalmids show great variation in the orbitosphenoid and a complex nasal
      capsule. The latter exhibits greater development of some nasal cartilages, which
      make it more complex than in C. lemniscatus. These characteristics might be
      related to microhabitat use and the well-developed olfactory and vomeronasal
      systems observed within this clade.

PMID- 22881277
TI  - Reproduction numbers for infections with free-living pathogens growing in the
      environment.
AB  - The basic reproduction number R(0) for a compartmental disease model is often
      calculated by the next generation matrix (NGM) approach. When the interactions
      within and between disease compartments are interpreted differently, the NGM
      approach may lead to different R(0) expressions. This is demonstrated by
      considering a susceptible-infectious-recovered-susceptible model with free-living
      pathogen (FLP) growing in the environment. Although the environment could play
      different roles in the disease transmission process, leading to different R(0)
      expressions, there is a unique type reproduction number when control strategies
      are applied to the host population. All R(0) expressions agree on the threshold
      value 1 and preserve their order of magnitude. However, using data for
      salmonellosis and cholera, it is shown that the estimated R(0) values are
      substantially different. This study highlights the utility and limitations of
      reproduction numbers to accurately quantify the effects of control strategies for
      infections with FLPs growing in the environment.

PMID- 22881278
TI  - Ultrafast detection and quantification of brain signaling molecules with carbon
      fiber microelectrodes.
AB  - Carbon fiber microelectrodes provide the ideal platform for performing ultrafast,
      selective measurements of electroactive brain molecules. This article highlights
      the current status of the use of carbon fiber microelectrodes in neurochemical
      measurements, outlining the most cutting edge findings and technological advances
      in amperometry and fast-scan cyclic voltammetry.

PMID- 22881279
TI  - Clinical and research experience with the Personal and Social Performance Scale
      and suggested modifications.

PMID- 22881280
TI  - Release of high-energy water as an essential driving force for the high-affinity
      binding of cucurbit[n]urils.
AB  - Molecular dynamics simulations and isothermal titration calorimetry (ITC)
      experiments with neutral guests illustrate that the release of high-energy water
      from the cavity of cucurbit[n]uril (CBn) macrocycles is a major determinant for
      guest binding in aqueous solutions. The energy of the individual encapsulated
      water molecules decreases with increasing cavity size, because larger cavities
      allow for the formation of more stable H-bonded networks. Conversely, the total
      energy of internal water increases with the cavity size because the absolute
      number of water molecules increases. For CB7, which has emerged as an ultrahigh
      affinity binder, these counteracting effects result in a maximum energy gain
      through a complete removal of water molecules from the cavity. A new design
      criterion for aqueous synthetic receptors has therefore emerged, which is the
      optimization of the size of cavities and binding pockets with respect to the
      energy and number of residing water molecules.

PMID- 22881281
TI  - Diabetes mellitus abrogates the cardioprotection of sufentanil against
      ischaemia/reperfusion injury by altering glycogen synthase kinase-3beta.
AB  - BACKGROUND: Sufentanil is widely used in clinical anaesthesia because of its
      protective effects against ischaemia/reperfusion injury. Diabetes mellitus
      elevates the activity of glycogen synthase kinase-3beta (GSK-3beta), thereby
      increasing the permeability of mitochondrial transition pore. This study
      investigated the role of GSK-3beta in ameliorating the cardioprotective effect of
      sufentanil post-conditioning in diabetic rats. METHODS: Streptozotocin-induced
      diabetic rats and age-matched non-diabetic rats were subjected to 30 min of
      ischaemia and 120 min of reperfusion. Five minutes before reperfusion, rats were
      administered one of the following: a vehicle, sufentanil (1 MUg/kg), or a GSK
      3beta inhibitor SB216763 (0.6 mg/kg). Myocardial infarct size, cardiac troponin
      I, and the activity of GSK-3beta were then assessed. RESULTS: Sufentanil post
      conditioning significantly reduced myocardial infarct size in the non-diabetic,
      but not in diabetic rats. SB216763 reduced infarct size in both diabetic and non
      diabetic animals. Sufentanil-induced phospho-GSK-3beta was reduced 5 min after
      reperfusion in diabetic rats, but not in non-diabetic rats. CONCLUSIONS:
      Sufentanil treatment was ineffective in preventing against ischaemia/reperfusion
      in diabetic rats, which is associated with the activation of GSK-3beta. Our
      results also suggest that direct inhibition of GSK-3beta may provide a strategy
      to protect diabetic hearts against ischaemia/reperfusion injury.

PMID- 22881282
TI  - Complex regional pain syndrome following protracted labour*.
AB  - Obstetric nerve palsies are common and long-term sequelae are fortunately rare.
      The development of a complex regional pain syndrome is an unusual and less
      reported complication of labour-related neuropathy. A 28-year-old primigravida
      who experienced prolonged labour and instrumental delivery under spinal
      anaesthesia complained of persisting weakness and numbness postpartum, affecting
      the left lower limb. Urgent magnetic resonance imaging demonstrated no
      abnormality and a common peroneal nerve injury was later confirmed by nerve
      conduction studies. Unfortunately, the neuropathy did not resolve as expected and
      oedema, burning paraesthesia and allodynia affecting the left foot developed
      within two weeks. She was treated with gabapentin, ibuprofen, topical capsaicin
      and regular physiotherapy. After six months, the foot drop had resolved and the
      chronic pain element was significantly diminished.

PMID- 22881283
TI  - Brain delivery of olanzapine by intranasal administration of transfersomal
      vesicles.
AB  - The aim of this study was to investigate the presence of a possible direct
      correlation between vesicle elasticity and the amount of drug reaching the brain
      intranasally. Therefore, transfersomes were developed using phosphatidylcholine
      (PC) as the lipid matrix and sodium deoxycholate (SDC), Span(r) 60, Cremophor(r)
      EL, Brij(r) 58, and Brij(r) 72 as surfactants. The influence of the type of
      surfactant and PC-to-surfactant ratio on vesicle morphology, size, membrane
      elasticity, drug entrapment, and in vitro drug release was studied. The prepared
      transfersomes were mainly spherical in shape, with diameters ranging from 310 to
      885 nm. Transfersomes containing SDC and Span 60 with optimum lipid-to-surfactant
      molar ratio showed suitable diameters (410 and 380 nm, respectively) and
      deformability indices (17.68 and 20.76 mL/sec, respectively). Values for absolute
      drug bioavailability in rat plasma for transfersomes containing SDC and those
      containing Span 60 were 24.75 and 51.35%, whereas AUC(0-360 min) values in rat
      brain were 22,334.6 and 36,486.3 ng/mL/min, respectively. The present study
      revealed that the deformability index is a parameter having a direct relation
      with the amount of the drug delivered to the brain by the nasal route.

PMID- 22881284
TI  - The effect of the charge-separating interface on exciton dynamics in
      photocatalytic colloidal heteronanocrystals.
AB  - Ultrafast transient absorption spectroscopy was used to investigate the nature of
      photoinduced charge transfer processes taking place in ZnSe/CdS/Pt colloidal
      heteronanocrystals. These nanoparticles consist of a dot-in-a-rod semiconductor
      domain (ZnSe/CdS) coupled to a Pt tip. Together the three components are designed
      to dissociate an electron-hole pair by pinning the hole in the ZnSe domain while
      allowing the electron to transfer into the Pt tip. Separated charges can then
      induce a catalytic reaction, such as the light-driven hydrogen production.
      Present measurements demonstrate that the internal electron-hole separation is
      fast and results in the localization of both charges in nonadjacent parts of the
      nanoparticle. In particular, we show that photoinduced holes become confined
      within the ZnSe domain in less than 2 ps, while electrons take approximately 15
      ps to transition into a Pt tip. More importantly, we demonstrate that the
      presence of the ZnSe dot within the CdS nanorods plays a key role both in
      enabling photoinduced separation of charges and in suppressing their backward
      recombination. The implications of the observed exciton dynamics to
      photocatalytic function of ZnSe/CdS/Pt heteronanocrystals are discussed.

PMID- 22881285
TI  - Association study of a polymorphism in clock gene PERIOD3 and risk of
      inflammatory bowel disease.
AB  - Altered body rhythmicity and deregulated clock gene expression may cause
      circadian disruption, which can lead to immune dysregulation and chronic
      inflammatory diseases. PERIOD3 (PER3) polymorphisms have been associated with
      circadian disruption and changed secretion of cytokines involved in chronic
      inflammation. Crohn's disease (CD) and ulcerative colitis (UC) are multifactorial
      diseases resulting from complex interaction among environmental/microbial factors
      and the intestinal immune system, triggering an abnormal immune response in
      genetically susceptible individuals. We evaluated the influence of a polymorphism
      of the clock gene PER3 on susceptibility and behavior of these inflammatory bowel
      diseases. The rs2797685 variant of the PER3 gene was assessed in 1082 CD and 972
      UC patients, 754 of whom had been diagnosed <18 yrs of age, and 1311 unrelated
      healthy controls. Allele and genotype frequencies of rs2797685 were significantly
      increased in both CD (p = 1.6 * 10(-4), odds ratio [OR] = 1.38, 95% confidence
      interval [CI]: 1.17-1.63) and UC (p = .012, OR = 1.25, 95% CI: 1.05-1.48)
      patients. Difference between frequency distributions remained statistically
      significant after stratifying the cohort according to age at diagnosis for CD,
      but not for UC. Statistically significant association was found between PER3
      polymorphism and use of immunosuppressive drugs in pediatric CD patients (p <
      .001) and with stricturing and fistulizing disease behavior in adult CD patients
      (p = .031). In conclusion, results of this association study suggest a possible
      role of PER3 polymorphism in determining susceptibility to CD and UC and
      phenotypic characteristics of CD. In particular, the rs2797685 variant of the
      PER3 gene is associated with a more aggressive form of CD, highlighted by higher
      use of immunosuppressants and more frequent stricturing and fistulizing disease
      behaviors, as well as early onset of CD. This is a descriptive study, and
      functional data are needed to prove a causal relationship; nonetheless,
      involvement of the clock gene machinery in the susceptibility and the behavior of
      inflammatory bowel diseases may suggest new pathophysiological mechanisms and new
      therapeutic approaches.

PMID- 22881286
TI  - Modelling family 2 cystatins and their interaction with papain.
AB  - Cystatins are extensively studied cysteine protease inhibitors, found in wide
      range of organisms with highly conserved structural folds. S-type of cystatins is
      well known for their abundance in saliva, high selectivity and poorer activity
      towards host cysteine proteases in comparison to their immediate ancestor
      cystatin C. Despite more than 90% sequence similarity, the members of this group
      show highly dissimilar binding affinity towards papain. Cystatin M/E is a potent
      inhibitor of legumain and papain like cysteine proteases and recognized for its
      involvement in skin barrier formation and potential role as a tumor suppressor
      gene. However, the structures of these proteins and their complexes with papain
      or legumain are still unknown. In the present study, we have employed
      computational methods to get insight into the interactions between papain and
      cystatins. Three-dimensional structures of the cystatins are generated by
      homology modelling, refined with molecular dynamics simulation, validated through
      numerous web servers and finally complexed with papain using ZDOCK algorithm in
      Discovery Studio. A high degree of shape complementarity is observed within the
      complexes, stabilized by numerous hydrogen bonds (HB) and hydrophobic
      interactions. Using interaction energy, HB and solvent accessible surface area
      analyses, we have identified a series of key residues that may be involved in
      papain-cystatin interaction. Differential approaches of cystatins towards papain
      are also noticed which are possibly responsible for diverse inhibitory activity
      within the group. These findings will improve our understanding of fundamental
      inhibitory mechanisms of cystatin and provide clues for further research.

PMID- 22881287
TI  - Uranyl bearing hybrid materials: synthesis, speciation, and solid-state
      structures.

PMID- 22881288
TI  - The natural history of hip development in cerebral palsy.
AB  - AIM: The purpose of this study was to evaluate a population-based radiographic
      hip surveillance programme for children with cerebral palsy (CP) and to assess
      the natural history of hip displacement. METHOD: The study comprised 335 children
      (188 males, 147 females), born during 2002 to 2006 in the 10 south-eastern
      counties in Norway. Their mean age at the first radiograph was 3 years (range 6mo
      7y 11mo) and the mean age at the most recent follow-up was 5 years 5 months.
      Distribution according to CP type was spastic hemiplegia in 38%, diplegia in 27%,
      quadriplegia in 21%, dyskinesia in 10%, and ataxia in 3%; Gross Motor Function
      Classification System (GMFCS) levels I to V were, 44%, 14%, 8%, 11%, and 23%
      respectively. Migration percentage (MP), acetabular index, and pelvic obliquity
      were measured on the radiographs. RESULTS: Hip displacement (MP>33%) occurred in
      26% of all children (subluxation in 22% and dislocation in 4%) and in 63% of
      those in GMFCS levels IV or V. Dislocation occurred in 14 children at a mean age
      of 4 years 5 months (range 1y 10mo-9y 7mo). The mean migration percentage was
      20.4% at the initial radiographs and 34.0% at the last follow-up. Mean
      progression in migration percentage increased markedly with decreasing functional
      level, from 0.2% per year at GMFCS level I to 9.5% at level V. INTERPRETATION:
      There is a pronounced trend towards hip displacement in nonambulant children.
      Close surveillance from age 1 to 2 years is needed to find the appropriate time
      for preventive surgery. Since 12% of the nonambulant children developed
      dislocation, our routines for hip surveillance need improvement.

PMID- 22881289
TI  - Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the
      astrocytic compartment.
AB  - The mechanisms responsible for pathological iron deposition in the aging and
      degenerating mammalian CNS remain poorly understood. The stress protein, HO-1
      mediates the degradation of cellular heme to biliverdin/bilirubin, free iron, and
      CO and is up-regulated in the brains of persons with Alzheimer's disease and
      Parkinson's disease. HO-1 induction in primary astroglial cultures promotes
      deposition of non-transferrin iron, mitochondrial damage and macroautophagy, and
      predisposes cocultured neuronal elements to oxidative injury. To gain a better
      appreciation of the role of glial HO-1 in vivo, we probed for aberrant brain iron
      deposition using Perls' method and dynamic secondary ion mass spectrometry in
      novel, conditional GFAP.HMOX1 transgenic mice that selectively over-express human
      HO-1 in the astrocytic compartment. At 48 weeks, the GFAP.HMOX1 mice exhibited
      increased deposits of glial iron in hippocampus and other subcortical regions
      without overt changes in iron-regulatory and iron-binding proteins relative to
      age-matched wild-type animals. Dynamic secondary ion mass spectrometry revealed
      abundant FeO- signals in the transgenic, but not wild-type, mouse brain that
      colocalized to degenerate mitochondria and osmiophilic cytoplasmic inclusions
      (macroautophagy) documented by TEM. Sustained up-regulation of HO-1 in astrocytes
      promotes pathological brain iron deposition and oxidative mitochondrial damage
      characteristic of Alzheimer's disease-affected neural tissues. Curtailment of
      glial HO-1 hyperactivity may limit iron-mediated cytotoxicity in aging and
      degenerating neural tissues.

PMID- 22881290
TI  - Lubrication and load-bearing properties of human salivary pellicles adsorbed ex
      vivo on molecularly smooth substrata.
AB  - In a series of Surface Force Balance experiments, material from human whole
      saliva was adsorbed to molecularly smooth mica substrata (to form an 'adsorbed
      salivary film'). Measurements were taken of normal (load bearing, F (n)) and
      shear (frictional, F (s)*) forces between two interacting surfaces. One
      investigation involved a salivary film formed by overnight adsorption from
      undiluted, centrifuged saliva, with the adsorbed film rinsed with pure water
      before measurement. Measurements were taken under pure water and 70 mM NaNO(3).
      In a second investigation, a film was formed from and measured under a solution
      of 7% filtered saliva in 10 mM NaNO(3). F (n) results for both systems showed
      purely repulsive layers, with an uncompressed thickness of 35-70 nm for the
      diluted saliva investigation and, prior to the application of shear, 11 nm for
      the rinsed system. F (s)* was essentially proportional to F (n) for all systems
      and independent of shear speed (in the range 100-2000 nm s(-1)), with
      coefficients of friction MU ~ 0.24 and MU ~ 0.46 for the unrinsed and rinsed
      systems, respectively. All properties of the rinsed system remained similar when
      the pure water measurement environment was changed to 70 mM NaNO(3). For all
      systems studied, shear gave rise to an approximately threefold increase in the
      range of normal forces, attributed to the ploughing up of adsorbed material
      during shear to form debris that stood proud of the adsorbed layer. The results
      provide a microscopic demonstration of the wear process for a salivary film under
      shear and may be of particular interest for understanding the implications for in
      vivo oral lubrication under conditions such as rinsing of the mouth cavity. The
      work is interpreted in light of earlier studies that showed a structural collapse
      and increase in friction for an adsorbed salivary film in an environment of low
      ionic strength.

PMID- 22881291
TI  - Evaluation of the impact of sequential microwave/ultrasound processing on the IgE
      binding properties of Pru p 3 in treated peach juice.
AB  - Peach lipid transfer protein (LTP) can cause severe allergic reactions to peach
      allergic patients. It belongs to the nonspecific LTPs family, a class of proteins
      extremely resistant both to proteolytic digestion and to high temperatures. Food
      processing can either drop or increase the allergenicity, depending on the
      process and on the food. As far as peach-derived products (pulp, juice) are
      concerned, it has been previously shown how thermal treatment performed in an
      autoclave does not decrease LTP allergenicity. In this work, it was attempted to
      investigate whether sequential microwave and ultrasound processing could affect
      the allergenicity of peach juice. Incubation with specific anti-Pru p 3 serum
      showed how treating peach peel with microwave at 140  degrees C and with
      ultrasound does not eliminate Pru p 3 IgE binding properties. The application of
      MW/US protocol on peach pulp appeared to be insufficient for the reduction of IgE
      binding to Pru p 3.

PMID- 22881292
TI  - Deproteinized natural rubber film forming polymeric solutions for nicotine
      transdermal delivery.
AB  - Film forming polymeric solutions were prepared from DNRL blended with MC, PVA, or
      SAG, together with dibutylphthalate or glycerine used as plasticizers. These
      formulations were easily prepared by simple mixing. In a preliminary step, in
      situ films were prepared by solvent evaporation in a Petri-dish. Their mechanical
      and physicochemical properties were determined. The in vitro release and skin
      permeation of nicotine dissolved in these blended polymers were investigated by a
      modified Franz diffusion cell. The formulations had a white milky appearance, and
      were homogeneous and smooth in texture. Their pH was suitable for usage in skin
      contact. The mechanical property of in situ films depended on the ingredients but
      all compatible films were in an amorphous phase. The DNRL/PVA was shown to be the
      most suitable mixture to form completed films. The in vitro release and skin
      permeation studies demonstrated a biphasic release that provided an initial rapid
      release followed by a constant release rate that fitted the Higuchi's model.
      Nicotine loaded DNRL/PVA series were selected for the stability test for 3
      months. These formulations needed to be kept at 4 degrees C in tight fitting
      containers. In conclusion, film forming polymeric solutions could be developed
      for transdermal nicotine delivery systems. 

PMID- 22881293
TI  - The effect of a cervical collar on the seal pressure of the LMA SupremeTM: a
      prospective, crossover trial.
AB  - For personnel inexperienced in airway management, supraglottic airway devices may
      be the first choice in an emergency. Changing head position is known to reduce
      the seal pressure of a laryngeal mask airway. The aim of this study was to
      investigate whether the use of a cervical collar improves the stability of
      airways secured with the LMA SupremeTM (The Laryngeal Mask Company Limited, Mahe,
      Seychelles). In this crossover trial, the primary endpoint was the difference in
      the seal pressure of the LMA Supreme in anaesthetised patients in maximum passive
      extension of the neck, with and without a cervical collar. The median (IQR
      [range]) seal pressure was 18 (13.8-22.1 [0-30]) cmH(2) O in maximum passive
      extension without a cervical collar. With a cervical collar in place, the seal
      pressure increased to 28 (22.8-30 [17-30]) cmH(2) O (p<0.001). In the neutral
      head position, the seal pressure was 22 (17.6-24.5 [12-30]) cmH(2) O without and
      27 (22-30 [12-30]) cmH(2) O with a cervical collar in place (p<0.001). We found
      that a cervical collar stabilises the airway with an LMA Supreme in place and we
      recommend this combination for (pre-hospital) emergency cases.

PMID- 22881294
TI  - Controlled self-assembly of multiple diastereomeric macrocyclic boronic esters
      composed of two chiral units.
AB  - Controlled construction of four out of five diastereomers of macrocyclic boronic
      ester was achieved in high yield by utilizing the self-assembly of two chiral
      components with the proper choice of reaction conditions. Three diastereomers
      could be constructed as enantiopure forms by properly changing the chirality
      combination between the two building blocks. Furthermore, the methodology could
      be applicable to the three-component self-assembly of enantiopure macrocyclic
      boronic esters having two different diboronic acid moieties.

PMID- 22881296
TI  - Pharmacological approaches in bipolar disorders and the impact on cognition: a
      critical overview.
AB  - OBJECTIVE: Historically, pharmacological treatments for bipolar disorders (BD)
      have been associated with neurocognitive side-effects. We reviewed studies which
      assessed the impact of several psychopharmacological drugs on the neurocognitive
      function of BD patients. METHOD: The PubMed database was searched for studies
      published between January 1980 and February 2011, using the following terms:
      bipolar, bipolar disorder, mania, manic episode, or bipolar depression, cross
      referenced with cognitive, neurocognitive, or neuropsychological, cross
      referenced with treatment. RESULTS: Despite methodological flaws in the older
      studies and insufficient research concerning the newer agents, some consistent
      findings emerged from the review; lithium appears to have definite, yet subtle,
      negative effects on psychomotor speed and verbal memory. Among the newer
      anticonvulsants, lamotrigine appears to have a better cognitive profile than
      carbamazepine, valproate, topiramate, and zonisamide. More long-term studies are
      needed to better understand the impact of atypical antipsychotics on BD patients'
      neurocognitive functioning, both in monotherapy and in association with other
      drugs. Other agents, like antidepressants and cognitive enhancers, have not been
      adequately studied in BD so far. CONCLUSION: Pharmacotherapies for BD should be
      chosen to minimize neurocognitive side-effects, which may already be compromised
      by the disease process itself. Neurocognitive evaluation should be considered in
      BD patients to better evaluate treatment impact on neurocognition. A
      comprehensive neuropsychological evaluation also addressing potential variables
      and key aspects such as more severe cognitive deficits, comorbidities,
      differential diagnosis, and evaluation of multiple cognitive domains in
      longitudinal follow-up studies are warranted.

PMID- 22881295
TI  - Intervertebral disc degeneration: evidence for two distinct phenotypes.
AB  - We review the evidence that there are two types of disc degeneration. 'Endplate
      driven' disc degeneration involves endplate defects and inwards collapse of the
      annulus, has a high heritability, mostly affects discs in the upper lumbar and
      thoracic spine, often starts to develop before age 30 years, usually leads to
      moderate back pain, and is associated with compressive injuries such as a fall on
      the buttocks. 'Annulus-driven' disc degeneration involves a radial fissure and/or
      a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar
      spine, develops progressively after age 30 years, usually leads to severe back
      pain and sciatica, and is associated with repetitive bending and lifting. The
      structural defects which initiate the two processes both act to decompress the
      disc nucleus, making it less likely that the other defect could occur
      subsequently, and in this sense the two disc degeneration phenotypes can be
      viewed as distinct.

PMID- 22881339
TI  - Indications for a protective function of beta2-glycoprotein I in thrombotic
      thrombocytopenic purpura.
AB  - It has been shown that beta(2) -glycoprotein I (beta(2) GPI) interacts with von
      Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the
      presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we
      speculated that beta(2) GPI might play a role in TTP. We found that beta(2) GPI
      plasma levels were significantly lower in acute and remission TTP patients than
      in normal controls, showing a direct correlation with ADAMTS 13 levels and an
      inverse correlation with the extent of VWF activation. In vitro flow experiments
      demonstrated that beta(2) GPI can block platelet adhesion to endothelial cell
      derived VWF strings. We confirmed the direct binding of beta(2) GPI to VWF by
      surface plasmon resonance, and determined that domain I of beta(2) GPI is the
      binding site of VWF A1 domain. Adhesion of beta(2) GPI to erythrocytes and
      platelets was increased in the presence of active VWF, indicating that beta(2)
      GPI may be cleared from the circulation during TTP episodes together with blood
      cells. Our findings suggest that beta(2) GPI may protect from the effects of
      hyper-functional VWF by inhibiting its interaction with platelets.

PMID- 22881340
TI  - Nonlinear photoluminescence imaging of isotropic and liquid crystalline
      dispersions of graphene oxide.
AB  - We report a visible-range nonlinear photoluminescence (PL) from graphene oxide
      (GO) flakes excited by near-infrared femtosecond laser light. PL intensity has
      nonlinear dependence on the laser power, implying a multiphoton excitation
      process, and also strongly depends on a linear polarization orientation of
      excitation light, being at maximum when it is parallel to flakes. We show that PL
      can be used for a fully three-dimensional label-free imaging of isotropic,
      nematic, and lamellar liquid crystalline dispersions of GO flakes in water. This
      nonlinear PL is of interest for applications in direct label-free imaging of
      composite materials and study of orientational ordering in mesomorphic phases
      formed by these flakes, as well as in biomedical and sensing applications
      utilizing GO.

PMID- 22881341
TI  - The role of salt concentration and magnesium binding in HIV-1 subtype-A and
      subtype-B kissing loop monomer structures.
AB  - The subtype-B monomers of the human immunodeficiency virus type-1 (HIV-1) have
      experimentally been shown to dimerize at high salt concentration or in the
      presence of magnesium, while the dimerization of the subtype-A monomers requires
      magnesium binding at the G273 or G274 phosphate groups regardless of salt
      concentration. We used explicit solvent molecular dynamics (MD) simulations to
      investigate the conformational changes in subtype-A and -B monomers in different
      salt concentrations, and we found that our MD simulation results are consistent
      with those of experiments. At low salt concentration, hairpin loop structures of
      both subtypes were deformed and bases in the hairpin loop were turned inside. At
      high salt concentrations, the subtype-B monomer maintained the hairpin loop shape
      and most bases in the hairpin loop pointed out, while the subtype-A monomer
      showed a severe deformation. We also found that the flanking bases in the subtype
      B stabilize the hairpin loop, while the flanking base G273 in the subtype-A
      caused a significant deformation. However, a bound magnesium ion at the G273 or
      G274 phosphate groups controlled the behavior of the G273 base and prevented the
      subtype-A monomer from deformation. We also applied restraints to both subtypes
      to examine the role of high salt concentration or magnesium binding. While
      restraints were applied, both subtypes at 0 M salt concentration maintained their
      shapes. However, when restraints were removed, they deformed significantly.
      Therefore, we suggest that the dimerization of both subtypes requires the proper
      conformation of the monomers which is induced by the appropriate salt strength
      and magnesium ion binding.

PMID- 22881343
TI  - Instability in a generalized Keller-Segel model.
AB  - We present a generalized Keller-Segel model where an arbitrary number of chemical
      compounds react, some of which are produced by a species, and one of which is a
      chemoattractant for the species. To investigate the stability of homogeneous
      stationary states of this generalized model, we consider the eigenvalues of a
      linearized system. We are able to reduce this infinite dimensional eigenproblem
      to a parametrized finite dimensional eigenproblem. By matrix theoretic tools, we
      then provide easily verifiable sufficient conditions for destabilizing the
      homogeneous stationary states. In particular, one of the sufficient conditions is
      that the chemotactic feedback is sufficiently strong. Although this mechanism was
      already known to exist in the original Keller-Segel model, here we show that it
      is more generally applicable by significantly enlarging the class of models
      exhibiting this instability phenomenon which may lead to pattern formation.

PMID- 22881342
TI  - Melanopsin gene variations interact with season to predict sleep onset and
      chronotype.
AB  - The human melanopsin gene has been reported to mediate risk for seasonal
      affective disorder (SAD), which is hypothesized to be caused by decreased photic
      input during winter when light levels fall below threshold, resulting in
      differences in circadian phase and/or sleep. However, it is unclear if melanopsin
      increases risk of SAD by causing differences in sleep or circadian phase, or if
      those differences are symptoms of the mood disorder. To determine if melanopsin
      sequence variations are associated with differences in sleep-wake behavior among
      those not suffering from a mood disorder, the authors tested associations between
      melanopsin gene polymorphisms and self-reported sleep timing (sleep onset and
      wake time) in a community sample (N = 234) of non-Hispanic Caucasian participants
      (age 30-54 yrs) with no history of psychological, neurological, or sleep
      disorders. The authors also tested the effect of melanopsin variations on
      differences in preferred sleep and activity timing (i.e., chronotype), which may
      reflect differences in circadian phase, sleep homeostasis, or both. Daylength on
      the day of assessment was measured and included in analyses. DNA samples were
      genotyped for melanopsin gene polymorphisms using fluorescence polarization. P10L
      genotype interacted with daylength to predict self-reported sleep onset
      (interaction p < .05). Specifically, sleep onset among those with the TT genotype
      was later in the day when individuals were assessed on longer days and earlier in
      the day on shorter days, whereas individuals in the other genotype groups (i.e.,
      CC and CT) did not show this interaction effect. P10L genotype also interacted in
      an analogous way with daylength to predict self-reported morningness (interaction
      p < .05). These results suggest that the P10L TT genotype interacts with
      daylength to predispose individuals to vary in sleep onset and chronotype as a
      function of daylength, whereas other genotypes at P10L do not seem to have
      effects that vary by daylength. A better understanding of how melanopsin confers
      heightened responsivity to daylength may improve our understanding of a broad
      range of behavioral responses to light (i.e., circadian, sleep, mood) as well as
      the etiology of disorders with seasonal patterns of recurrence or exacerbation.

PMID- 22881345
TI  - Mixing and using dantrolene for simulated malignant hyperthermia crisis.

PMID- 22881344
TI  - Periodontal tissue engineering with stem cells from the periodontal ligament of
      human retained deciduous teeth.
AB  - BACKGROUND AND OBJECTIVE: Periodontal ligament stem cells from human permanent
      teeth (PePDLSCs) have been investigated extensively in periodontal tissue
      engineering and regeneration. However, little knowledge is available on the
      periodontal ligament stem cells from human retained deciduous teeth (DePDLSCs).
      This study evaluated the potential of DePDLSCs in periodontal tissue
      regeneration. MATERIAL AND METHODS: DePDLSCs were isolated and purified by
      limited dilution. The characteristics of DePDLSCs were evaluated and compared
      with PePDLSCs both in vitro and in vivo. RESULTS: DePDLSCs presented a higher
      proliferation rate and colony-forming capacity than PePDLSCs in vitro. During the
      osteogenic induction, alkaline phosphatase (ALP) activity, mineralized matrix
      formation and expression of mineralization-related genes, including runt-related
      transcription factor 2 (RUNX2), ALP, collagen type I (COLI) and osteocalcin (OCN)
      were significantly enhanced in DePDLSCs compared with PePDLSCs. Furthermore,
      DePDLSC cell sheets showed a stronger synthesis of collagen type I in the
      extracellular matrix than did PePDLSC cell sheets. After in vivo transplantation,
      DePDLSC cell sheets recombined with human dentin blocks were able to generate new
      cementum/periodontal ligament-like tissues. CONCLUSION: Our findings suggest that
      DePDLSCs can be used as a promising candidate for periodontal tissue engineering.

PMID- 22881346
TI  - Analysis of high mass-to-charge ions in a quadrupole ion trap mass spectrometer
      via an end-cap quadrupolar direct current downscan.
AB  - A method for performing mass-selective instability analysis in a three
      dimensional (3-D) quadrupole ion trap is described that involves scanning a
      direct current (dc) voltage applied to the end-cap electrodes while holding the
      radio frequency (rf) potential at a fixed value. Rather than eject at the beta(z)
      = 1 instability line by ramping the amplitude of the drive rf potential applied
      to the ring electrode, as with the original mass-selective instability scan, this
      approach effects ion ejection along the beta(z) = 0 instability line in a process
      identical in principle (though it varies in its method of implementation) to the
      previously termed "downscan" ( Todd  ,   J. F. J.     ; Penman  ,   A. D.     ;  
      Smith  ,   R. D. Int. J. Mass Spectrom. Ion Processes     1991  ,   106  ,  
      117 - 135  ). A linear scan of the dc amplitude results in a nonlinear mass
      scale, unlike the conventional resonance ejection scan with a linear scan of the
      rf amplitude, and the ejection of ions in the direction of high mass-to-charge
      (m/z) to low m/z. However, the downscan offers some advantages over the
      traditional rf scan for ions of high m/z values. These include a larger scannable
      mass range, as well as the opportunity for improved resolution at high mass.
      These characteristics are demonstrated with ions of m/z 10(4)-10(5).

PMID- 22881347
TI  - The inwardly rectifying potassium channel Kir1.1: development of functional
      assays to identify and characterize channel inhibitors.
AB  - The renal outer medullary potassium (ROMK) channel is a member of the inwardly
      rectifying family of potassium (Kir) channels. ROMK (Kir1.1) is predominantly
      expressed in kidney where it plays a major role in the salt reabsorption process.
      Loss-of-function mutations in the human Kir1.1 channel are associated with
      antenatal Bartter's syndrome type II, a life-threatening salt and water balance
      disorder. Heterozygous carriers of Kir1.1 mutations associated with antenatal
      Bartter's syndrome have reduced blood pressure and a decreased risk of developing
      hypertension by age 60. These data suggest that Kir1.1 inhibitors could represent
      novel diuretics for the treatment of hypertension. Because little is known about
      the molecular pharmacology of Kir1.1 channels, assays that provide a robust,
      reliable readout of channel activity-while operating in high-capacity mode-are
      needed. In the present study, we describe high-capacity, 384- and 1,536-well
      plate, functional thallium flux, and IonWorks electrophysiology assays for the
      Kir1.1 channel that fulfill these criteria. In addition, 96-well (86)Rb(+) flux
      assays were established that can operate in the presence of 100% serum, and can
      provide an indication of the effect of a serum shift on compound potencies. The
      ability to grow Madin-Darby canine kidney cells expressing Kir1.1 in Transwell
      supports provides a polarized cell system that can be used to study the mechanism
      of Kir1.1 inhibition by different agents. All these functional Kir1.1 assays
      together can play an important role in supporting different aspects of drug
      development efforts during lead identification and/or optimization.

PMID- 22881348
TI  - The importance of screening for internalizing symptoms, inattention, and
      cognitive difficulties in childhood-onset myotonic dystrophy.

PMID- 22881350
TI  - A quality by design approach using artificial intelligence techniques to control
      the critical quality attributes of ramipril tablets manufactured by wet
      granulation.
AB  - Quality by design (QbD) is an essential part of the modern approach to
      pharmaceutical quality. This study was conducted in the framework of a QbD
      project involving ramipril tablets. Preliminary work included identification of
      the critical quality attributes (CQAs) and critical process parameters (CPPs)
      based on the quality target product profiles (QTPPs) using the historical data
      and risk assessment method failure mode and effect analysis (FMEA). Compendial
      and in-house specifications were selected as QTPPs for ramipril tablets. CPPs
      that affected the product and process were used to establish an experimental
      design. The results thus obtained can be used to facilitate definition of the
      design space using tools such as design of experiments (DoE), the response
      surface method (RSM) and artificial neural networks (ANNs). The project was aimed
      at discovering hidden knowledge associated with the manufacture of ramipril
      tablets using a range of artificial intelligence-based software, with the
      intention of establishing a multi-dimensional design space that ensures
      consistent product quality. At the end of the study, a design space was developed
      based on the study data and specifications, and a new formulation was optimized.
      On the basis of this formulation, a new laboratory batch formulation was prepared
      and tested. It was confirmed that the explored formulation was within the design
      space.

PMID- 22881351
TI  - Ocean acidification and coral reefs: effects on breakdown, dissolution, and net
      ecosystem calcification.
AB  - The persistence of carbonate structures on coral reefs is essential in providing
      habitats for a large number of species and maintaining the extraordinary
      biodiversity associated with these ecosystems. As a consequence of ocean
      acidification (OA), the ability of marine calcifiers to produce calcium carbonate
      (CaCO(3)) and their rate of CaCO(3) production could decrease while rates of
      bioerosion and CaCO(3) dissolution could increase, resulting in a transition from
      a condition of net accretion to one of net erosion. This would have negative
      consequences for the role and function of coral reefs and the eco-services they
      provide to dependent human communities. In this article, we review estimates of
      bioerosion, CaCO(3) dissolution, and net ecosystem calcification (NEC) and how
      these processes will change in response to OA. Furthermore, we critically
      evaluate the observed relationships between NEC and seawater aragonite saturation
      state (Omega(a)). Finally, we propose that standardized NEC rates combined with
      observed changes in the ratios of dissolved inorganic carbon to total alkalinity
      owing to net reef metabolism may provide a biogeochemical tool to monitor the
      effects of OA in coral reef environments.

PMID- 22881352
TI  - Reflections about chance in my career, and on the top-down regulated world.
AB  - Paraphrasing Pasteur, in scientific work Fortuna favors only the prepared mind.
      This is illustrated by my career after an incidental escape from the former
      German East Prussia just ahead of the Red Army, my switch in Kiel from zoology to
      oceanography, and my learning of a vacancy in Seattle. Treated here are the
      accidental discovery of upwelling during the southwest monsoon along India's west
      coast, studies of benthic polychaetous annelids in the Oregonian zoogeographic
      province, the discovery of phytoplankton blooms and an absence of upwelling
      during the northeast monsoon in the northern Arabian Sea, and an ocean-wide
      description of the seasonality of satellite-derived chlorophyll. My admonition is
      that grazing rather than cell division rate regulates the abundance and size
      composition of phytoplankton and affects the dynamics of the understudied
      zooplankton. I end with a pessimistic view about predicting the vertical flux of
      particulate organic matter from the euphotic layer with an accuracy useful for
      deep-sea carbon budgets.

PMID- 22881353
TI  - Recalcitrant dissolved organic carbon fractions.
AB  - Marine dissolved organic carbon (DOC) exhibits a spectrum of reactivity, from
      very fast turnover of the most bioavailable forms in the surface ocean to long
      lived materials circulating within the ocean abyss. These disparate reactivities
      group DOC by fractions with distinctive functions in the cycling of carbon,
      ranging from support of the microbial loop to involvement in the biological pump
      to a hypothesized major source/sink of atmospheric CO(2) driving paleoclimate
      variability. Here, the major fractions constituting the global ocean's
      recalcitrant DOC pool are quantitatively and qualitatively characterized with
      reference to their roles in carbon biogeochemistry. A nomenclature for the
      fractions is proposed based on those roles.

PMID- 22881354
TI  - Photophysiological expressions of iron stress in phytoplankton.
AB  - Iron is essential for all life, but it is particularly important to
      photoautotrophs because of the many iron-dependent electron transport components
      in photosynthetic membranes. Since the proliferation of oxygenic photosynthesis
      in the Archean ocean, iron has been a scarce commodity, and it is now recognized
      as a limiting resource for phytoplankton over broad expanses of the open ocean
      and even in some coastal/continental shelf waters. Iron stress does not impair
      photochemical or carbon fixation efficiencies, and in this respect it resembles
      the highly tuned photosynthetic systems of steady-state macronutrient-limited
      phytoplankton. However, iron stress does present unique photophysiological
      challenges, and phytoplankton have responded to these challenges through major
      architectural changes in photosynthetic membranes. These evolved responses
      include overexpression of photosynthetic pigments and iron-economic pathways for
      ATP synthesis, and they result in diagnostic fluorescence properties that allow a
      broad appraisal of iron stress in the field and even the detection of iron stress
      from space.

PMID- 22881355
TI  - Biocultural considerations of food cravings and aversions: an introduction.
AB  - Food is fundamental to our existence as humans, but assertions about the kinds of
      foods that are appealing or repulsive vary widely. This thematic issue deals with
      assessments of food as desirable, or not, in order to understand the complex
      reasons why some foods are strongly craved while others are avoided. To do this,
      the five articles in this issue situate food cravings and aversions
      bioculturally, in the contexts of our history as a species, in the landscape of
      cultural heritage, and in the individual life course. By exploring both the
      biological and cultural mechanisms that shape food preferences, we reveal the
      complex and important underpinnings of the critical endeavor of food selection.

PMID- 22881356
TI  - Gastronomic nostalgia: Salvadoran immigrants' cravings for their ideal meal.
AB  - Immigrants typically express cravings for the food of their homeland, but for
      undocumented and temporarily documented Salvadoran immigrants living in the
      United States, the hunger for their traditional cuisine is particularly poignant.
      To cope with a history of food scarcity in El Salvador and their documentation
      liminality in the United States, Salvadoran immigrants in this study crave
      symbolically rich foods. Salvadoran women provide these foods by recreating for
      their families an ideal Salvadoran meal into which they "groom" meanings of an
      imagined past and a hoped for present and future. Salvadoran immigrants'
      cravings, more cultural than physiological, are not readily satisfied, thus
      contributing to the overconsumption of food and the high rate of overweight among
      first-generation Salvadoran-American children.

PMID- 22881357
TI  - Appetite sensations and nausea and vomiting in pregnancy: an overview of the
      explanations.
AB  - We review information about the potential mechanisms underlying nausea and
      vomiting in pregnancy (NVP), food cravings, and/or aversions in pregnancy. In
      addition to providing overviews about genetic predispositions and hormonal
      associations with appetite sensations and NVP, we review two functional
      explanations: the "maternal and embryo protection" and the "placental growth and
      development" hypotheses. We conclude with a discussion about the kinds of data
      that would enable us to better evaluate the relative advantages and disadvantages
      of NVP across disparate resource and ecological conditions.

PMID- 22881358
TI  - Patterns of nausea, vomiting, aversions, and cravings during pregnancy on Pemba
      Island, Zanzibar, Tanzania.
AB  - The function(s) of nausea and vomiting in pregnancy (NVP) and its accompanying
      aversions and cravings remain unresolved. Neither of the two major adaptive
      hypotheses, "maternal/embryo protection" and "placental growth," have been tested
      using data from a low-income country. We examined NVP in a cross-sectional study
      of 427 pregnant women. The prevalence of NVP was comparable to resource-rich
      contexts: 69.6%, 55.5%, 70.0%, and 64.9% reported NVP, gustatory aversions,
      olfactory aversions, and cravings, respectively. The prevalence of all phenomena
      was highest in the first trimester. The timing and characteristics of NVP,
      aversions, and cravings were most consistent with the protection hypothesis.

PMID- 22881359
TI  - Appetite sensations in pregnancy among agropastoral women in rural Tanzania.
AB  - Women all over the globe report physical and appetite sensations in early
      pregnancy, and this study contributes to this growing literature by reporting on
      the appetite sensations experienced by pregnant women from rural Tanzania.
      Appetite changes associated with 545 pregnancies were compiled from surveys
      conducted to report on the prevalence of appetite loss, nausea, vomiting,
      dizziness, joint pain, cravings, aversions, and pica experienced by agropastoral
      women from rural north-central Tanzania. In addition to these symptoms, specific
      craved and aversive food groups are described. Statistical associations among
      appetite sensations, NVP, and birthweight are tested. The only symptom associated
      with a lower average birth weight for newborns was vomiting. In addition to
      investigating micronutrient content and chemical properties of specific food and
      non-food items, future research should include assessing relationships among
      various appetite sensations and short- and long-term health outcomes for both the
      mother and child.

PMID- 22881360
TI  - A biocultural framework for examining maternal cravings and aversions among
      pastoral women in east Africa.
AB  - Food preferences during pregnancy result from a complex set of biocultural
      interactions with important implications for maternal and child health. This
      article explores the social context of maternal food choice in marginal
      environments of East Africa. Biocultural data collected among Turkana and Datoga
      women living in Kenya and Tanzania indicate there is a significant social context
      to food choice that influences the types of food that women report craving and
      the food that is consumed. Our framework argues for a deeper understanding of how
      culture shapes food preferences and how marginalization can constrain access to
      favored and healthy foods.

PMID- 22881361
TI  - The role of imaging techniques in the management of multiple myeloma.
AB  - Bone disease is the major feature of multiple myeloma (MM). Imaging is required
      for correct staging, in the follow-up after treatment and, as recently
      highlighted, is predictor of prognosis. In the near future, whole-body X-Ray may
      be replaced by more sensitive techniques, such as whole-body low-dose
      computerized tomography (CT). Magnetic resonance imaging (MRI) is the gold
      standard method for assessing bone marrow infiltration of the spine, predicting
      the risk of vertebral fracture and distinguishing between benign and malignant
      osteoporosis. Positron emission tomography (PET) with CT (PET/CT) provides
      important information about the extent of whole-body disease, including soft
      tissue masses, and is the best tool to distinguish between active or inactive
      disease after therapy. Both MRI and PET/CT are predictors of clinical outcome. A
      prospective use of these newer imaging techniques in both clinical trials and
      clinical practice may help optimize MM management in the near future.

PMID- 22881362
TI  - Cost-effectiveness of everolimus vs sunitinib in treating patients with advanced,
      progressive pancreatic neuroendocrine tumors in the United States.
AB  - BACKGROUND: Everolimus (Afinitor) and sunitinib (Sutent) were recently approved
      to treat patients with advanced, progressive pancreatic neuroendocrine tumors
      (pNETs). (Afinitor is a registered trademark of Novartis Pharmaceuticals
      Corporation, East Hanover, NJ, USA; Sutent is a registered trademark of Pfizer
      Inc., New York, NY, USA.) This analysis examined the projected cost-effectiveness
      of everolimus vs sunitinib in this setting from a US payer perspective. METHODS:
      A semi-Markov model was developed to simulate a cohort of patients with advanced,
      progressive pNET and to estimate the cost per life-year gained (LYG) and per
      quality-adjusted life-year (QALY) gained when treating with everolimus vs
      sunitinib. Efficacy data were based on a weight-adjusted indirect comparison of
      the agents using phase 3 trial data. Model health states included: stable disease
      with no adverse events, stable disease with adverse events, disease progression,
      and death. Therapy costs were based on wholesale acquisition cost. Other costs
      such as physician visits, tests, hospitalizations, and adverse event costs were
      obtained from literature and/or primary research. Utility inputs were based on
      primary research. Sensitivity analyses were conducted to test the model's
      robustness. RESULTS: In the base-case analysis, everolimus was associated with an
      incremental 0.448 LYG (0.304 QALYs) at an incremental cost of $12,673, resulting
      in an incremental cost-effectiveness ratio (ICER) of $28,281/LYG ($41,702/QALY
      gained). The ICER fell within the cost per QALY range for many widely used
      oncology drugs. Sensitivity analyses demonstrated that, overall, there is a trend
      that everolimus is cost-effective compared to sunitinib in this setting.
      LIMITATIONS: Results of the indirect analysis were not statistically significant
      (p > 0.05). Assumptions that treatment patterns are the same across therapies may
      not represent real-world practice. CONCLUSIONS: While the analysis is limited by
      its reliance on an indirect comparison of two phase 3 studies, everolimus is
      expected to be cost-effective relative to sunitinib in advanced, progressive
      pNET.

PMID- 22881363
TI  - Alignment-independent comparison of binding sites based on DrugScore potential
      fields encoded by 3D Zernike descriptors.
AB  - Analyzing protein binding sites provides detailed insights into the biological
      processes proteins are involved in, e.g., into drug-target interactions, and so
      is of crucial importance in drug discovery. Herein, we present novel alignment
      independent binding site descriptors based on DrugScore potential fields. The
      potential fields are transformed to a set of information-rich descriptors using a
      series expansion in 3D Zernike polynomials. The resulting Zernike descriptors
      show a promising performance in detecting similarities among proteins with low
      pairwise sequence identities that bind identical ligands, as well as within
      subfamilies of one target class. Furthermore, the Zernike descriptors are robust
      against structural variations among protein binding sites. Finally, the Zernike
      descriptors show a high data compression power, and computing similarities
      between binding sites based on these descriptors is highly efficient.
      Consequently, the Zernike descriptors are a useful tool for computational binding
      site analysis, e.g., to predict the function of novel proteins, off-targets for
      drug candidates, or novel targets for known drugs.

PMID- 22881364
TI  - Cross-sectional data on soft tissue morphometry of the growing hand and fingers
      of dextral individuals 5-65 years old.
AB  - This study examines both hands of right-handed (dextral) subjects 5-65 years old
      in order to define the separate growth trajectories of digit lengths (2D-5D) and
      hand widths; to assess how 2D : 4D and other digit ratios also vary with age; and
      to test whether lengths are influenced by gender dimorphism and lateral
      (right/left) asymmetry. Calliper measurements were made from hand photocopies.
      Growth patterns were analysed by linear regression and correlation, main and
      interaction effects of age and gender were resolved by analysis of variance, and
      lateral asymmetries were identified by paired tests. All digits, and hand width,
      grew in a biphasic pattern in both hands, and inflection points between phases
      showed gender dimorphism. In the early fast-growing phase, male digits grew over
      a longer period than those in females, before switching to a slower growth phase
      during which gender dimorphism became more exaggerated. In right hands, age
      differences in digit ratios were confined to 2D : 4D and, except for 4D : 5D,
      females tended to show larger ratios than males. In left hands, all ratios
      (except 3D : 5D) varied with age and gender influenced only 2D : 4D, 2D : 5D and
      3D : 5D. Again, ratios were greater in females. In females, 2D was longer in the
      right hand of older subjects, whilst 3D, 4D and 5D tended to be shorter in the
      right hand of younger subjects. No asymmetries were seen in 2D, 3D or 4D in
      males, but 5D tended to be shorter on the right in the group 9-12 years old.
      Finally, hand width tended to be greater in females on the right at 9-65 years
      old, and in males on the right at 18-23 years old. A further novel finding was
      that certain relationships (inflection points, correlation coefficients and
      gender differences in digit lengths) seemed to follow gradients running from 2D
      to 5D. It is tempting to speculate that these are manifestations of the antero
      posterior gradients established by signalling events that control digit
      development and patterning in utero.

PMID- 22881365
TI  - Why triple bonds protect acenes from oxidation and decomposition.
AB  - An experimental and computational study on the impact of functional groups on the
      oxidation stability of higher acenes is presented. We synthesized anthracenes,
      tetracenes, and pentacenes with various substituents at the periphery, identified
      their photooxygenation products, and measured the kinetics. Furthermore, the
      products obtained from thermolysis and the kinetics of the thermolysis are
      investigated. Density functional theory is applied in order to predict reaction
      energies, frontier molecular orbital interactions, and radical stabilization
      energies. The combined results allow us to describe the mechanisms of the
      oxidations and the subsequent thermolysis. We found that the alkynyl group not
      only enhances the oxidation stability of acenes but also protects the resulting
      endoperoxides from thermal decomposition. Additionally, such substituents
      increase the regioselectivity of the photooxygenation of tetracenes and
      pentacenes. For the first time, we oxidized alkynylpentacenes by using chemically
      generated singlet oxygen ((1)O(2)) without irradiation and identified a 6,13
      endoperoxide as the sole regioisomer. The bimolecular rate constant of this
      oxidation amounts to only 1 * 10(5) s(-1) M(-1). This unexpectedly slow reaction
      is a result of a physical deactivation of (1)O(2). In contrast to unsubstituted
      or aryl-substituted acenes, photooxygenation of alkynyl-substituted acenes
      proceeds most likely by a concerted mechanism, while the thermolysis is well
      explained by the formation of radical intermediates. Our results should be
      important for the future design of oxidation stable acene-based semiconductors.

PMID- 22881366
TI  - Evolutionary dynamics and strong Allee effects.
AB  - We describe the dynamics of an evolutionary model for a population subject to a
      strong Allee effect. The model assumes that the carrying capacity k(u), inherent
      growth rate r(u), and Allee threshold a(u) are functions of a mean phenotypic
      trait u subject to evolution. The model is a plane autonomous system that
      describes the coupled population and mean trait dynamics. We show bounded orbits
      equilibrate and that the Allee basin shrinks (and can even disappear) as a result
      of evolution. We also show that stable non-extinction equilibria occur at the
      local maxima of k(u) and that stable extinction equilibria occur at local minima
      of r(u). We give examples that illustrate these results and demonstrate other
      consequences of an Allee threshold in an evolutionary setting. These include the
      existence of multiple evolutionarily stable, non-extinction equilibria, and the
      possibility of evolving to a non-evolutionary stable strategy (ESS) trait from an
      initial trait near an ESS.

PMID- 22881367
TI  - Prevalence of frailty in community-dwelling older persons: a systematic review.
AB  - OBJECTIVES: To systematically compare and pool the prevalence of frailty,
      including prefrailty, reported in community-dwelling older people overall and
      according to sex, age, and definition of frailty used. DESIGN: Systematic review
      of the literature using the key words elderly, aged, frailty, prevalence, and
      epidemiology. SETTING: Cross-sectional data from community-based cohorts.
      PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: In the
      studies that were found, frailty and prefrailty were measured according to
      physical phenotype and broad phenotype, the first defining frailty as a purely
      physical condition and the second also including psychosocial aspects. RESULTS:
      Reported prevalence in the community varies enormously (range 4.0-59.1%). The
      overall weighted prevalence of frailty was 10.7% (95% confidence interval (CI) =
      10.5-10.9; 21 studies; 61,500 participants). The weighted prevalence was 9.9% for
      physical frailty (95% CI = 9.6-10.2; 15 studies; 44,894 participants) and 13.6%
      for the broad phenotype of frailty (95% CI = 13.2-14.0; 8 studies; 24,072
      participants) (chi-square (chi(2) ) = 217.7, degrees of freedom (df)=1, P <
      .001). Prevalence increased with age (chi(2) = 6067, df = 1, P < .001) and was
      higher in women (9.6%, 95% CI = 9.2-10.0%) than in men (5.2%, 95% CI = 4.9-5.5%;
      chi(2) = 298.9 df = 1, P < .001). CONCLUSION: Frailty is common in later life,
      but different operationalization of frailty status results in widely differing
      prevalence between studies. Improving the comparability of epidemiological and
      clinical studies constitutes an important step forward.

PMID- 22881368
TI  - Maraviroc observational study: the impact of expanded resistance testing and
      clinical considerations for antiretroviral regimen selection in treatment
      experienced patients.
AB  - Maraviroc (MVC) use has trailed that of other post-2006 antiretroviral therapy
      (ART) options for treatment-experienced patients. We explored the impact of free
      tropism testing on MVC utilization in our cohort and explored barriers to MVC
      utilization. The Maraviroc Outcomes Study (MOS) is an investigator-initiated
      industry-sponsored trial where consecutive ART-experienced patients receiving
      routine care with viral loads >=1,000 copies/ml, and whose provider requested
      resistance testing and received standardized resistance testing (SRT; phenotype,
      genotype, coreceptor/tropism). Sociodemographic, clinical, and ART
      characteristics of those receiving SRT were compared to a historical cohort (HC).
      Subsequently, providers were surveyed regarding factors influencing selection of
      salvage ART therapy. The HC (n=165) had resistance testing 7/08-9/09, while
      prospective SRT (n=83) patients were enrolled 9/09-8/10. In the HC, 92% had
      genotypes, 2% had tropism assays, and 62% (n=102) changed ART after resistance
      testing (raltegravir 37%, etravirine 25%, darunavir 24%, MVC 1%). In the SRT
      cohort, 57% (n=48) changed regimens after standardized resistance testing
      (darunavir 48%, raltegravir 40%, and etravirine 19%). CCR5-tropic virus was
      identified in 43% of the SRT group, and MVC was used in 10% [or 20% of R5 tropic
      patients who underwent a subsequent regimen change (n=25)], a statistically
      significant (p=0.01) increase in utilization. The factors most strongly
      influencing utilization were unique patient circumstances (60%), clinical
      experience (55%), and potential side effects (40%). The addition of routine
      tropism testing to genotypic/phenotypic testing was associated with increased MVC
      utilization, raising the possibility that tropism testing may present a barrier
      to MVC use; however, additional barriers exist, and merit further evaluation.

PMID- 22881369
TI  - Serum creatinine detection by a conducting-polymer-based electrochemical sensor
      to identify allograft dysfunction.
AB  - Kidney transplant recipients who have abnormally high creatinine levels in their
      blood often have allograft dysfunction secondary to rejection. Creatinine has
      become the preferred marker for renal dysfunction and is readily available in
      hospital clinical settings. We developed a rapid and accurate polymer-based
      electrochemical point-of-care (POC) assay for creatinine detection from whole
      blood to identify allograft dysfunction. The creatinine concentrations of 19
      blood samples from transplant recipients were measured directly from clinical
      serum samples by the conducting polymer-based electrochemical (EC) sensor arrays.
      These measurements were compared to the traditional clinical laboratory assay.
      The time required for detection was <5 min from sample loading. Sensitivity of
      the detection was found to be 0.46 mg/dL of creatinine with only 40 MUL sample in
      the creatinine concentration range of 0 mg/dL to 11.33 mg/dL. Signal levels that
      were detected electrochemically correlated closely with the creatinine blood
      concentration detected by the UCLA Ronald Reagan Medical Center traditional
      clinical laboratory assay (correlation coefficient = 0.94). This work is
      encouraging for the development of a rapid and accurate POC device for measuring
      creatinine levels in whole blood.

PMID- 22881370
TI  - Effects of temperature on circadian clock and chronotype: an experimental study
      on a passerine bird.
AB  - Daily schedules of many organisms, including birds, are thought to affect
      fitness. Timing in birds is based on circadian clocks that have a heritable
      period length, but fitness consequences for individuals in natural environments
      depend on the scheduling of entrained clocks. This chronotype, i.e., timing of an
      individual relative to a zeitgeber, results from interactions between the
      endogenous circadian clock and environmental factors, including light conditions
      and ambient temperature. To understand contributions of these factors to timing,
      we studied daily activity patterns of a captive songbird, the great tit (Parus
      major), under different temperature and light conditions. Birds were kept in a
      light (L)-dark (D) cycle (12.5 L:11.5 D) at either 8 degrees C or 18 degrees C
      with ad libitum access to food and water. We assessed chronotype and subsequently
      tested birds at the same temperature under constant dim light (LL(dim)) to
      determine period length of their circadian clock. Thermal conditions were then
      reversed so that period length was measured under both temperatures. We found
      that under constant dim light conditions individuals lengthened their free
      running period at higher temperatures by 5.7 +/- 2.1 min (p = .002). Under LD,
      birds kept at 18 degrees C started activity later and terminated it much earlier
      in the day than those kept under 8 degrees C. Overall, chronotype was slightly
      earlier under higher temperature, and duration of activity was shorter.
      Furthermore, individuals timed their activities consistently on different days
      under LD and over the two test series under LL(dim) (repeatability from .38 to
      .60). Surprisingly, period length and chronotype did not show the correlation
      that had been previously found in other avian species. Our study shows that body
      clocks of birds are precise and repeatable, but are, nonetheless, affected by
      ambient temperature.

PMID- 22881371
TI  - Monounsaturated fatty acids are required for membrane translocation of protein
      kinase C-theta induced by lipid overload in skeletal muscle.
AB  - Protein kinase C (PKC) activation induced by diacylglycerols (DAGs) is one of the
      sequels of the dysregulation of intramuscular lipid metabolism and is thought to
      play an important role in the development of insulin resistance (IR). We tested
      the hypothesis that DAGs with different acyl chains have different biological
      effects and that DAG species enriched in monounsaturated fatty acids (MUFA) act
      as better activators of PKC. The experiments were performed in vitro on C2C12
      myotubes treated with palmitate (16:0), stearate (18:0) or oleate (18:1) and in
      vivo on the skeletal muscles of rats fed high-fat (HF), high-tristearin (TS) or
      high-triolein (TO) diets. To define the importance of endogenously synthesized
      MUFA on DAG-induced PKCtheta activation, we performed experiments on stearoyl-CoA
      desaturase 1 knockout mice (SCD1-/-) as well. The results show that the content
      of total DAGs and the levels of saturated DAG species are significantly increased
      in both insulin-resistant (16:0, HF and TO) and highly insulin-sensitive (18:0
      and TS) groups. An increase in MUFA-containing DAGs levels was most constantly
      related to increase in PKCtheta membrane translocation and IR. In the muscles of
      MUFA-deficient SCD1-/- mice, the DAG content and the induction of PKCtheta
      translocation by the HF diet were significantly reduced. Collectively, our data
      from both the cell and animal experiments show that DAGs composed of 16:1 and/or
      18:1, rather than the levels of total or saturated DAGs, are related to PKCtheta
      membrane translocation. Moreover, our results show that the availability of
      dietary MUFA and/or the activity of endogenous desaturases play an important role
      in muscle DAG accumulation.

PMID- 22881372
TI  - Differentiation of complex lipid isomers by radical-directed dissociation mass
      spectrometry.
AB  - Contemporary lipidomics protocols are dependent on conventional tandem mass
      spectrometry for lipid identification. This approach is extremely powerful for
      determining lipid class and identifying the number of carbons and the degree of
      unsaturation of any acyl-chain substituents. Such analyses are however, blind to
      isomeric variants arising from different carbon-carbon bonding motifs within
      these chains including double bond position, chain branching, and cyclic
      structures. This limitation arises from the fact that conventional, low energy
      collision-induced dissociation of even-electron lipid ions does not give rise to
      product ions from intrachain fragmentation of the fatty acyl moieties. To
      overcome this limitation, we have applied radical-directed dissociation (RDD) to
      the study of lipids for the first time. In this approach, bifunctional molecules
      that contain a photocaged radical initiator and a lipid-adducting group, such as
      4-iodoaniline and 4-iodobenzoic acid, are used to form noncovalent complexes
      (i.e., adduct ions) with a lipid during electrospray ionization. Laser
      irradiation of these complexes at UV wavelengths (266 nm) cleaves the carbon
      iodine bond to liberate a highly reactive phenyl radical. Subsequent activation
      of the nascent radical ions results in RDD with significant intrachain
      fragmentation of acyl moieties. This approach provides diagnostic fragments that
      are associated with the double bond position and the positions of chain-branching
      in glycerophospholipids, sphingomyelins and triacylglycerols and thus can be used
      to differentiate isomeric lipids differing only in such motifs. RDD is
      demonstrated for well-defined lipid standards and also reveals lipid structural
      diversity in olive oil and human very-low density lipoprotein.

PMID- 22881373
TI  - Paraoxonase 1 activity in multiple sclerosis patients during mitoxantrone
      therapy.
AB  - OBJECTIVES: It has been implicated in many studies that reactive oxygen species
      play a role in the development of demyelination in multiple sclerosis (MS).
      Paraoxonase 1 (PON1) is an antioxidant enzyme that protects cell membranes
      against oxidative modification. Mitoxantrone is a cytotoxic drug approved for the
      treatment of MS with adverse effects associated potentially with an increased
      level of oxidative stress. The aim of this study was to assess the influence of
      mitoxantrone therapy on PON1 activity in patients with MS. METHODS: A studied
      group included 26 patients with secondary progressive MS, 16 women and 10 men.
      The blood was collected before the beginning of the therapy as well as after 6
      and 12 months. Patients were receiving mitoxantrone every 12 weeks. Serum PON1
      activity was assayed using two synthetic substrates: paraoxon and phenyl acetate.
      RESULTS: Paraoxonase 1 activity toward paraoxon and phenyl acetate and lipid
      profile did not change significantly in patients receiving mitoxantrone.
      CONCLUSIONS: Mitoxantrone therapy does not influence PON1 activity.

PMID- 22881375
TI  - Angiotensinogen gene M235T and T174M polymorphisms and susceptibility of pre
      eclampsia: a meta-analysis.
AB  - There are controversies in reports on the association of the angiotensinogen
      (AGT) gene polymorphisms with the risk of developing pre-eclampsia (PE). We
      performed a meta-analysis to examine the association between the AGT
      polymorphisms and PE risk: M235T (31 studies involving 2555 patients and 6114
      controls) and T174M (six studies involving 681 patients and 2076 controls). For
      the M235T polymorphism, the TT genotype increased the PE risk as compared to the
      MM genotype (odds ratio 1.61, 95% confidence intervals 1.22-2.14, P= 0.001). When
      stratified by ethnicity, the TT genotype remained significantly associated with
      higher PE risk in Caucasians and Mongolians but not in Africans. Similar results
      were also obtained under all three genetic models of the M235T polymorphism. For
      the T174M polymorphism, no significant association was found in the comparisons
      (MT vs. TT and MM vs. TT) and under any genetic models. The analysis excluding
      the highly significant Hardy-Weinberg equilibrium-violating studies and
      sensitivity analysis further strengthened the validity of these associations. No
      publication bias was observed in this study. This meta-analysis demonstrates that
      the AGT M235T polymorphism is significantly associated with PE whereas the T174M
      polymorphism is not.

PMID- 22881374
TI  - Genome-wide association and linkage study in the Amish detects a novel candidate
      late-onset Alzheimer disease gene.
AB  - To identify novel late-onset Alzheimer disease (LOAD) risk genes, we have
      analysed Amish populations of Ohio and Indiana. We performed genome-wide SNP
      linkage and association studies on 798 individuals (109 with LOAD). We tested
      association using the Modified Quasi-Likelihood Score test and also performed two
      point and multipoint linkage analyses. We found that LOAD was significantly
      associated with APOE (P= 9.0 * 10-6) in all our ascertainment regions except for
      the Adams County, Indiana, community (P= 0.55). Genome-wide, the most strongly
      associated SNP was rs12361953 (P= 7.92 * 10-7). A very strong, genome-wide
      significant multipoint peak [recessive heterogeneity multipoint LOD (HLOD) =
      6.14, dominant HLOD = 6.05] was detected on 2p12. Three additional loci with
      multipoint HLOD scores >3 were detected on 3q26, 9q31 and 18p11. Converging
      linkage and association results, the most significantly associated SNP under the
      2p12 peak was at rs2974151 (P= 1.29 * 10-4). This SNP is located in CTNNA2, which
      encodes catenin alpha 2, a neuronal-specific catenin known to have function in
      the developing brain. These results identify CTNNA2 as a novel candidate LOAD
      gene, and implicate three other regions of the genome as novel LOAD loci. These
      results underscore the utility of using family-based linkage and association
      analyses in isolated populations to identify novel loci for traits with complex
      genetic architecture.

PMID- 22881376
TI  - Low-density lipoprotein receptor gene familial hypercholesterolemia variant
      database: update and pathological assessment.
AB  - Familial hypercholesterolemia (FH) is caused predominately by variants in the low
      density lipoprotein receptor gene (LDLR). We report here an update of the UCL
      LDLR variant database to include variants reported in the literature and in-house
      between 2008 and 2010, transfer of the database to LOVDv.2.0 platform
      (https://grenada.lumc.nl/LOVD2/UCL-Heart/home.php?select_db=LDLR) and
      pathogenicity analysis. The database now contains over 1288 different variants
      reported in FH patients: 55% exonic substitutions, 22% exonic small
      rearrangements (<100 bp), 11% large rearrangements (>100 bp), 2% promoter
      variants, 10% intronic variants and 1 variant in the 3' untranslated sequence.
      The distribution and type of newly reported variants closely matches that of the
      2008 database, and we have used these variants (n= 223) as a representative
      sample to assess the utility of standard open access software (PolyPhen, SIFT,
      refined SIFT, Neural Network Splice Site Prediction Tool, SplicePort and
      NetGene2) and additional analyses (Single Amino Acid Polymorphism database,
      analysis of conservation and structure and Mutation Taster) for pathogenicity
      prediction. In combination, these techniques have enabled us to assign with
      confidence pathogenic predictions to 8/8 in-frame small rearrangements and 8/9
      missense substitutions with previously discordant results from PolyPhen and SIFT
      analysis. Overall, we conclude that 79% of the reported variants are likely to be
      disease causing.

PMID- 22881378
TI  - Prevalence and diversity of Synergistetes taxa in periodontal health and disease.
AB  - BACKGROUND AND OBJECTIVE: Members of the phylum Synergistetes have previously
      been identified within periodontitis subgingival plaque and are considered
      putative periodontopathogens. This study compared the diversity of subginigval
      Synergistetes in a cohort of subjects with periodontitis (n = 10) vs.
      periodontitis-free controls (n = 10). MATERIAL AND METHODS: Pooled subgingival
      plaque samples from all deep periodontal pockets or all sulci were collected from
      the periodontitis and periodontitis-free subjects, respectively. Bacterial 16S
      rRNA genes were PCR-amplified from purified subgingival plaque DNA using a
      Synergistetes 'selective' primer set. PCR products were cloned and sequenced to
      analyze the prevalence and diversity of Synergistetes operational taxonomic units
      (OTUs) present in plaque samples of both subject groups. RESULTS: A total of 1030
      non-chimeric 16S rRNA clones were obtained, of which 162 corresponded to members
      of the phylum Synergistetes. A significantly larger number of Synergistetes
      clones were obtained from periodontitis subgingival plaque than from
      periodontitis-free controls (25.4% vs. 5.9%, p < 0.001). All Synergistetes clones
      corresponded to cluster A oral Synergistetes, and fell into 31 OTUs (99% sequence
      identity cut-off). Twenty-nine Synergistetes OTUs were detected in the
      periodontitis group while eight were detected in the periodontitis-free group (p
      < 0.001). Five Synergistetes OTUs; including one OTU corresponding to the
      recently-characterized species Fretibacterium fastidiosum, were more prevalent in
      the periodontitis subjects (p < 0.05). CONCLUSION: OTUs belonging to oral
      Synergistetes cluster A were more readily detectable and were more diverse in
      subgingival plaque from periodontitis subjects compared with periodontitis-free
      controls. Specific Synergistetes OTUs appear to be associated with periodontitis.

PMID- 22881379
TI  - Delayed delivery in twins: an infectious abortion and a subsequent preterm
      delivery without histological signs of chorioamnionitis.

PMID- 22881380
TI  - "We Can't Give Up Now": global health optimism and polio eradication in Pakistan.
AB  - The Polio Eradication Initiative, the largest coordinated public health project
      in history, is currently facing serious difficulties. For years, it has tried and
      failed to eliminate polio from its last strongholds in Afghanistan, Pakistan, and
      Nigeria. Drawing on document analysis as well as participant observation and
      interviews in Pakistan, Atlanta, Geneva, and Montreal, I explore how officials in
      the Polio Eradication Initiative systematically devalued or quieted evidence that
      eradication was not achievable and emphasized evidence that it was achievable,
      thus creating a string of optimistic projections. Polio eradication's culture of
      optimism ensures the continuation of the project by convincing donors and
      officials alike that eradication is immanent. At the same time, it prevents open,
      objective analysis of the problems the project faces.

PMID- 22881381
TI  - The task of the HIV translator: transforming global AIDS knowledge in an
      awareness workshop.
AB  - The globalization of standardized knowledge about HIV and AIDS depends in part on
      local AIDS awareness educators who receive training from national and
      international organizations and then, ideally, disseminate what they have
      learned. In this article I analyze textual and observational data from a five-day
      introductory AIDS awareness workshop in rural Papua New Guinea. Although the
      instructor adhered to the handbook provided by the National AIDS Council for much
      of the information, she departed from it significantly when informing
      participants about the "root causes" of HIV's spread and in giving them advice
      about prevention. I explicate where her extratextual knowledge came from as well
      as its overall message to target audiences. I suggest that textual silences in
      AIDS awareness handbooks can motivate local HIV translators to embark on a kind
      of semiosis-the ongoing production of new, hybrid knowledge about HIV.

PMID- 22881382
TI  - Weaving networks of responsibility: community work in development programs in
      rural Malawi.
AB  - The need to cope with the impact of the AIDS epidemic on communities in Africa
      has resulted in the emergence of numerous community health and development
      programs. Initiated by governments, international nongovernmental organizations
      (NGOs), and local organizations, such programs target local communities with the
      goal of building care and support mechanisms in the local level. Based on
      ethnographic field research in rural Malawi, and drawing from the cross
      disciplinary debate on development work, the article explores the work of an NGO
      offering health and care programs to orphans and vulnerable children. Through
      analyzing the organization's scope of work, the article demonstrates how the NGO
      acts to structure local social networks as instruments of care and offers a new
      reading of the role of NGOs in which the limitations of development work and the
      work of NGOs are understood within their local context and not only in the
      context of broad cultural critique.

PMID- 22881383
TI  - Culture, history, and health in an Australian aboriginal community: the case of
      utopia.
AB  - The poor health of Indigenous Australians is well established. However, the
      health of residents of one remote community in the Northern Territory of
      Australia called Utopia has been found recently to be much better than expected.
      In this article, we draw on historical anthropological research to explain this
      finding. We trace how cultural and social structures were maintained through
      changing eras of government policy from the 1930s, and show how these structures
      strengthened psychosocial determinants of health. We argue that the mainstream
      psychosocial determinants of social cohesion and self-efficacy are usefully
      reconceptualized in an Indigenous context as connectedness to culture and land,
      and collective efficacy, respectively. Continuity of cultural and social
      structures into the 1940s was facilitated by a combination of factors including
      the relatively late colonial occupation, the intercultural practices typical of
      the pastoral industry, the absence of a mission or government settlement, and the
      individual personalities and histories of those connected to Utopia.

PMID- 22881384
TI  - Total synthesis of 7-deoxy-6-O-methylfusarentin featuring a chelation-controlled
      1,3-Reetz-Keck-type allylation.
AB  - The total synthesis of 7-deoxy-6-O-methylfusarentin (1) and a formal synthesis of
      7-deoxy-6,8-O-dimethylfusarentin (2) has been successfully achieved in 10 steps.
      The described tactic underscores a diastereoselective strategy which incorporates
      a single acyclic reaction based on the initial stereocenter by means of a 1,3
      chelation-controlled Reetz-Keck-type allylation.

PMID- 22881385
TI  - Cognitive-behavioral phenotype or comorbid disorder? The case of attention
      deficit-hyperactivity disorder in neurofibromatosis type 1.

PMID- 22881386
TI  - Single-agent lenalidomide in relapsed/refractory mantle cell lymphoma: results
      from a UK phase II study suggest activity and possible gender differences.
AB  - We present data from a phase II study investigating a novel treatment strategy
      for relapsed/refractory mantle cell lymphoma (MCL). Twenty-six patients received
      lenalidomide 25 mg/d (days 1-21 of a 28-d cycle) for up to 6 cycles followed by
      low-dose maintenance lenalidomide (15 mg) in responding patients. Eight patients
      achieved complete or partial response to give an overall response rate of 31%
      with median response duration of 22.2 months [95% confidence interval (CI) 0.0
      53.6] and median progression-free survival (PFS) of 3.9 months (95% CI 0.0-11.1).
      An additional six patients (23%) achieved stable disease. Eleven patients
      received maintenance with median PFS of 14.6 months (95% CI 7.3-21.9).
      Correlative studies showed that peripheral T and Natural Killer (NK) cells
      increased in responding patients by 40-60% over the first 6 cycles with an
      initial dip in NK cells suggestive of tumour infiltration. Peripheral regulatory
      T cells were increased in MCL patients (P = 0.001) and expanded further following
      lenalidomide. Sequential plasma analysis showed increased IL12 p40 and IL7
      alongside decreased MMP9, IL10, and adiponectin. Finally, a significant
      correlation (P = 0.02) between gender and response suggested that female MCL
      patients were more sensitive to lenalidomide than males. In summary, we confirm
      the activity, safety and immunomodulatory properties of lenalidomide in MCL and
      highlight its potential as a low-dose maintenance agent.

PMID- 22881387
TI  - Effects of tuberculosis on the kinetics of CD4(+) T cell count among HIV-infected
      patients who initiated antiretroviral therapy early after tuberculosis treatment.
AB  - The effects of tuberculosis (TB) on the kinetics of CD4(+) T cells among HIV
      infected individuals with early combination antiretroviral therapy (cART) after
      TB therapy initiation are poorly characterized. We conducted a case-control study
      with 15 HIV-TB-coinfected patients who initiated TB treatment and early cART, and
      30 controls without TB who had similar CD4(+) T cell counts and viral loads at
      the time of starting cART. We compared the rate of CD4(+) T cell increase for 5
      years after cART. The time to CD4(+) T cell increase >250 cells/mm(3) was
      significantly slower in HIV-TB-coinfected patients (p=0.015, by log rank test).
      HIV-TB-coinfected patients had significantly lower median CD4(+) T cell counts at
      5 years after cART (p=0.048). The difference in CD4(+) T cell increase was
      observed only during the first 6 months after cART initiation (p=0.002). These
      data suggest that TB slows the rate of CD4(+) T cell recovery at an early period
      after cART. The effects of TB on the long-term immunity of HIV-infected patients
      should be further evaluated.

PMID- 22881388
TI  - Striated muscle fiber apoptosis after experimental tendon lesion in a rat model.
AB  - Tendon lesions induce muscular atrophy, the nature of which has not yet been
      clearly related to lesion etiology and entity. In the present study, tendon and
      muscle alterations were assessed after experimental tendon lesion of the
      Infraspinatus muscle in young rats. The consequences of lesions differed on the
      basis of both extension and injured tissue vascularization, that is apoptosis
      and/or degeneration, differing mainly by energy demands: apoptosis requires high
      energy levels (proportional to vascular supply), but degeneration does not. It is
      well known that tendons are poorly supplied with blood compared with muscular
      masses, which are abundantly vascularized. Five weeks after tendon surgical
      section, tendon/muscle samples were taken for TUNEL and transmission electron
      microscopy. The structural results reported here identified different
      tendon/muscle alterations: degeneration of tendon without signs of apoptosis, and
      atrophy of muscle fibers due only to apoptosis. This led to the formulation of
      the following hypothetical sequence of events: a tendon lesion, not recovering
      quickly due to the poor tendon blood supply, results in degeneration of the
      injured tendon, which, in turn, induces a partial disuse of the muscle mass,
      which consequently atrophies (proportionally to the severity of tendon lesion) by
      striated muscular fiber apoptosis. The authors suggest that the different
      behavior of the two tissues depends on the marked difference in their
      vascularization.

PMID- 22881389
TI  - Development and optimization of dextromethorphan hydrobromide oral disintegrating
      tablets: effect of formulation and process variables.
AB  - Orally disintegrating tablets (ODTs), which disintegrate rapidly (<1 min) in the
      mouth and do not require water for administration, have become a very popular
      dosage form. The study aims to develop a simple and inexpensive method of
      manufacturing ODTs of a sparingly water-soluble drug, Dextromethorphan
      hydrobromide. Two factors, three levels (3(2)) full factorial design was used to
      optimize the diluent, microcrystalline cellulose (X(1)) and superdisintegrant,
      croscarmellose sodium (X(2)) concentrations. Disintegration time, hardness and
      T(50) values for all the formulations varied from 12.5 to 152.6 s, 3.58 to 4.92
      kp and 0.8 to 2.8 min, respectively. The results indicated that the selected
      variables have a strong influence on disintegration time, hardness and T(50) of
      the ODTs. The manufactured ODTs formula composed of 30% microcrystalline
      cellulose in combination with 3% croscarmellose sodium was chosen as optimized
      formula, as it showed the lowest disintegration time (12.5 +/- 1.22 s), low T(50)
      (0.8 min.) and hard tablets (4.92 +/- 0.28 kp) amongst other tested ODTs
      formulations. Hardness of DM ODTs was not affected by changing the type of
      superdisintegrant and lubricant. The disintegration time was significantly (p <
      0.05) increased by using sodium starch glycolate instead of croscarmellose
      sodium.

PMID- 22881391
TI  - Relative importance of risk factors for coronary heart disease--the Hordaland
      Homocysteine study.
AB  - OBJECTIVES: The aim was to rank coronary heart disease (CHD) risk factors
      according to their importance in predicting CHD morbidity and mortality using a
      scale-independent statistical approach. DESIGN: We studied 15 515 community
      dwelling adults in a population-based cohort established during 1992-93 in
      Western Norway. Participants were 40-42 and 65-67 years old at baseline and were
      followed through 2006. Endpoints were non-fatal/fatal acute myocardial infarction
      (AMI) and CHD death. Each factor was rank transformed and scaled to the range 0-5
      before estimation of Cox models. Hazard ratios (HR) may thus be interpreted as HR
      per quintile increment for each factor, and the magnitude of the HR was used to
      rank the risk factors according to strength. RESULTS: Total cholesterol and
      triglycerides were important risk factors for both CHD death and non-fatal/fatal
      AMI only in the middle-aged group. Risk factors were generally stronger in the
      middle-aged, except total homocysteine which was significantly associated with
      CHD death in the oldest group only. The only significant difference between men
      and women was found for single living which was an important risk factor for non
      fatal/fatal AMI in middle-aged women but not in middle-aged men. CONCLUSIONS: We
      have demonstrated a simple method for direct and scale-independent comparison of
      the strength of both categorical and continuous risk factors. The importance of
      individual risk factors differed substantially between the two age groups.

PMID- 22881392
TI  - Surface-enhanced raman scattering detection of pH with silica-encapsulated 4
      mercaptobenzoic acid-functionalized silver nanoparticles.
AB  - Sensors based upon surface-enhanced Raman spectroscopy (SERS) are attractive
      because they have narrow, vibrationally specific spectral peaks that can be
      excited using red and near-infrared light which avoids photobleaching, penetrates
      tissue, and reduces autofluorescence. Several groups have fabricated pH
      nanosensors by functionalizing silver or gold nanoparticle surfaces with an
      acidic molecule and measuring the ratio of protonated to deprotonated Raman
      bands. However, a limitation of these sensors is that macromolecules in
      biological systems can adsorb onto the nanoparticle surface and interfere with
      measurements. To overcome this interference, we encapsulated pH SERS sensors in a
      30 nm thick silica layer with small pores which prevented bovine serum albumin
      (BSA) molecules from interacting with the pH-indicating 4-mercaptobenzoic acid (4
      MBA) on the silver surfaces but preserved the pH-sensitivity. Encapsulation also
      improved colloidal stability and sensor reliability. The noise level corresponded
      to less than 0.1 pH units from pH 3 to 6. The silica-encapsulated functionalized
      silver nanoparticles (Ag-MBA@SiO(2)) were taken up by J774A.1 macrophage cells
      and measured a decrease in local pH during endocytosis. This strategy could be
      extended for detecting other small molecules in situ.

PMID- 22881393
TI  - High-resolution enabled TMT 8-plexing.
AB  - Isobaric mass tag-based quantitative proteomics strategies such as iTRAQ and TMT
      utilize reporter ions in the low-mass range of tandem MS spectra for relative
      quantification. The number of samples that can be compared in a single experiment
      (multiplexing) is limited by the number of different reporter ions that can be
      generated by differential stable isotope incorporation ((15)N, (13)C) across the
      reporter and the mass balancing parts of the reagents. Here, we demonstrate that
      a higher multiplexing rate can be achieved by utilizing the 6 mDa mass difference
      between (15)N- and (13)C-containing reporter fragments, in combination with high
      resolution mass spectrometry. Two variants of the TMT127 and TMT129 reagents are
      available; these are distinguished by the position and the nature of the
      incorporated stable isotope in the reporter portions of the labels (TMT127L,
      (12)C(8)H(16)(15)N(1)(+); TMT127H, (12)C(7)(13)C(1)H(16)(14)N(1)(+); TMT129L,
      (12)C(6)(13)C(2)H(16)(15)N(1)(+); and TMT129H, (12)C(5)(13)C(3)H(16)(14)N(1)(+)).
      We demonstrate that these variants can be baseline-resolved in Orbitrap Elite
      higher-energy collision-induced dissociation spectra recorded with a 96 ms
      transient enabling comparable dynamic range, precision, and accuracy of
      quantification as 1 Da spaced reporter ions. The increased multiplexing rate
      enabled determination of inhibitor potencies in chemoproteomic kinase assays
      covering a wider range of compound concentrations in a single experiment,
      compared to conventional 6-plex TMT-based assays.

PMID- 22881394
TI  - Insulin use in elderly adults: risk of hypoglycemia and strategies for care.
AB  - Hypoglycemia is a significant problem in elderly adults with diabetes mellitus.
      Elderly individuals with diabetes mellitus are at greater risk than younger
      adults for hypoglycemic events. Several factors contribute to this risk,
      including the high prevalence of comorbidities, polypharmacy, cognitive
      impairment, and concomitant use of agents that interfere with glucose metabolism.
      To minimize the risk of hypoglycemia and maximize the benefits of glycemic
      control, guidelines typically recommend individualizing glycosylated hemoglobin
      (HbA1c) targets based on life expectancy, functional status, and individual
      goals. Although many individuals with type 2 diabetes mellitus will ultimately
      require insulin therapy to achieve and maintain glycemic control, earlier insulin
      initiation in elderly individuals may be warranted, particularly in those with
      renal, cardiovascular, or hepatic concerns that could interfere with the use of
      oral agents. There are few data on the use of insulin-or other glucose-lowering
      agents-in elderly adults, but limited evidence suggests that the use of insulin,
      especially insulin analogs, may be appropriate in this population. Insulin
      analogs offer a better pharmacokinetic profile, greater convenience, and less
      variable glycemic control than human insulin. Because of the high prevalence of
      cognitive impairment and other geriatric syndromes in elderly adults, clinicians
      should perform a comprehensive assessment of patients' ability to administer and
      monitor insulin therapy and recognize and treat hypoglycemia.

PMID- 22881395
TI  - General Allee effect in two-species population biology.
AB  - The main objective of this work is to present a general framework for the notion
      of the strong Allee effect in population models, including competition,
      mutualistic, and predator-prey models. The study is restricted to the strong
      Allee effect caused by an inter-specific interaction. The main feature of the
      strong Allee effect is that the extinction equilibrium is an attractor. We show
      how a 'phase space core' of three or four equilibria is sufficient to describe
      the essential dynamics of the interaction between two species that are prone to
      the Allee effect. We will introduce the notion of semistability in planar
      systems. Finally, we show how the presence of semistable equilibria increases the
      number of possible Allee effect cores.

PMID- 22881396
TI  - Role of hydrophobic and ionic forces in the movement of S4 of the Shaker
      potassium channel.
AB  - Voltage-gated ion (K(+), Na(+), Ca(2+)) channels contain a pore domain (PD)
      surrounded by four voltage sensing domains (VSD). Each VSD is made up of four
      transmembrane helices, S1-S4. S4 contains 6-7 positively charged residues
      (arginine/lysine) separated two hydrophobic residues, whereas S1-S3 contribute to
      two negatively charged clusters. These structures are conserved among all members
      of the voltage-gated ion channel family and play essential roles in voltage
      gating. The role of S4 charged residues in voltage gating is well established:
      During depolarization, they move out of the membrane electric field, exerting a
      mechanical force on channel gates, causing them to open. However, the role of the
      intervening hydrophobic residues in voltage sensing is unclear. Here we studied
      the role of these residues in the prototypical Shaker potassium channel. We have
      altered the physicochemical properties of both charged and hydrophobic positions
      of S4 and examined the effect of these modifications on the gating properties of
      the channel. For this, we have introduced cysteines at each of these positions,
      expressed the mutants in Xenopus oocytes, and examined the effect of in situ
      addition of charge, via Cd(2+), on channel gating by two-electrode voltage clamp.
      Our results reveal a face of the S4 helix (comprising residues L358, L361, R365
      and R368) where introduction of charge at hydrophobic positions destabilises the
      closed state and removal of charges from charged positions has an opposite
      effect. We propose that hydrophobic residues play a crucial role in limiting
      gating to a physiological voltage range.

PMID- 22881397
TI  - Low-cost fabrication of paper-based microfluidic devices by one-step plotting.
AB  - In this technical note, we describe a facile method for one-step fabrication of
      paper-based microfluidic devices, by simply using commercially available
      permanent markers and metal templates with specific patterns. The fabrication
      process involves only a single step of plotting pattern in paper; it can be
      typically finished within 1 min. The ink marks formed in the patterned paper will
      act as the hydrophobic barriers to define the hydrophilic flow paths or separate
      test zones. Various paper devices can be created by using different templates
      with corresponding patterns. Transparent adhesive tape-sandwiched devices could
      protect their assay surfaces from potential contamination. In the proof-of
      concept experiments, circular paper test zones (~3 mm diameter) were fabricated
      for colorimetric and quantification detection of prostate-specific antigen (PSA)
      as a model target, based on dot-immunogold staining assays coupled with gold
      enhancement amplification. Several serum specimens were additionally evaluated
      with this new approach and the results were compared with the commercial
      chemiluminescence immunoassay, validating its feasibility of practical
      applications. Such a one-step plotting method for paper patterning does not
      require any specialized equipments and skills, is quite inexpensive and rapid,
      and thus holds great potential to find wide applications especially in remote
      regions and resource-limited environments such as small laboratories and private
      clinics.

PMID- 22881398
TI  - Determination of deamidation artifacts introduced by sample preparation using 18O
      labeling and tandem mass spectrometry analysis.
AB  - The sites and levels of Asn deamidation in proteins are often determined by LC-MS
      analysis of peptides obtained from enzymatic digestion. However, deamidation that
      occurs during sample preparation steps results in overestimation of the original
      level of deamidation. The inherent deamidation and those introduced by sample
      preparation can be differentiated by preparing samples in (18)O water. When using
      H(2)(18)O, the formation of isoAsp and Asp by Asn deamidation during sample
      preparation results in a molecular weight increase of 3 Da due to the
      incorporation of the (18)O atom to the side chains of isoAsp or Asp; in contrast,
      inherent deamidation only results in a molecular weight increase of 1 Da. In
      addition, up to two (18)O atoms can also be incorporated into the peptide C
      terminal carboxyl group during enzymatic digestion. Therefore, the 2 Da molecular
      weight difference at the deamidation sites can only be used to differentiate
      deamidation that occurs prior to or during sample preparation under conditions
      that a fixed number of (18)O atoms are incorporated into the peptide C-terminal
      carboxyl groups. Otherwise, it is challenging to apply this procedure because of
      the resulting complicated isotopic distributions. Here, a new procedure of using
      (18)O-water for sample preparation coupled with tandem mass spectrometry (MS/MS)
      was established to calculate the deamidation artifacts. In this method, b ions
      were used for the calculation of Asn deamidation that occurred prior to or during
      sample preparation, which eliminated the complicated factor of various number of
      (18)O-atoms to the peptide carboxyl groups. This procedure has the potential to
      be applied under the general peptide mapping conditions.

PMID- 22881399
TI  - Continuous cell separation using dielectrophoresis through asymmetric and
      periodic microelectrode array.
AB  - The study presents a dielectrophoretic cell separation method via three
      dimensional (3D) nonuniform electric fields generated by employing a periodic
      array of discrete but locally asymmetric triangular bottom microelectrodes and a
      continuous top electrode. Traversing through the microelectrodes, heterogeneous
      cells are electrically polarized to experience different strengths of positive
      dielectrophoretic forces, in response to the 3D nonuniform electric fields. The
      cells that experience stronger positive dielectrophoresis are streamed further in
      the perpendicular direction to the fluid flow, leaving the cells that experience
      weak positive dielectrophoresis, which continue to traverse the microelectrode
      array essentially along the laminar flow streamlines. The proposed method has
      achieved 87.3% pure live cells harvesting efficiency from a live/dead NIH-3T3
      cells mixture, and separation of MG-63 cells from erythrocytes with a separation
      efficiency of 82.8%. The demonstrated cell separation shows promising
      applications of the DEP separator for cell separation in a continuous mode.

PMID- 22881400
TI  - Development of a sensitive microarray immunoassay for the quantitative analysis
      of neuropeptide Y.
AB  - A direct competitive immunoassay in an antibody microarray format was developed
      for the sensitive detection of neuropeptide Y (NPY) and employed in the analysis
      of NPY in human sweat samples. This is the first demonstration that antibody
      microarray, as a powerful multiplex analysis tool, can be used for the sensitive
      determination of NPY and potentially other neuropeptides. 400 pg/mL of
      dibiotinylated NPY and 0.1 mg/mL spotting capture antibody were found to offer
      the best performance, yielding a sensitivity of 50 pg/mL and a linear dynamic
      range of 0.1-100 ng/mL for NPY. Evaluation of matrix effects by using artificial
      sweat revealed that dialysis is necessary for analyzing NPY in human sweat
      samples with microarray immunoassay. In a preliminary application, 50-210 pg/mL
      of NPY was detected in sweat samples collected with Macroduct collectors. This
      study indicates that antibody microarrays can be used for NPY analysis and that
      human sweat could be a valuable sample source for biomarker and proteomics
      studies, especially when noninvasive human sample collection is preferable.

PMID- 22881401
TI  - Polyaniline-based highly sensitive microbial biosensor for selective detection of
      lindane.
AB  - A highly sensitive, selective, and rapid, whole-cell-based electrochemical
      biosensor was developed for detection of the persistent organochlorine pesticide
      gamma-hexachlorocyclohexane (gamma-HCH), commonly known as lindane. The gene
      linA2 encoding the enzyme gamma-hexachlorocyclohexane (HCH) dehydrochlorinase
      (LinA2), involved in the initial steps of lindane (gamma-HCH) biotransformation,
      was cloned and overexpressed in  Escherichia coli . The lindane-biodegrading  E.
      coli  cells were immobilized on polyaniline film. The rapid and selective
      degradation of lindane and concomitant generation of hydrochloric acid by the
      recombinant  E. coli  cells in the microenvironment of polyaniline led to a
      change in its conductivity, which was monitored by pulsed amperometry. The
      biosensor could detect lindane in the part-per-trillion concentration range with
      a linear response from 2 to 45 ppt. The sensor was found to be selective to all
      the isomers of hexachlorocyclohexane (HCH) and to pentachlorocyclohexane (PCCH)
      but did not respond to other aliphatic and aromatic chlorides or to the end
      product of lindane degradation, i.e., trichlorobenzene (TCB). The sensor also did
      not respond to other commonly used organochlorine pesticides like DDT and DDE. On
      the basis of experimental results, a rationale has been proposed for the
      excellent sensitivity of polyaniline as a pH sensor for detection of H(+) ions
      released in its microenvironment.

PMID- 22881402
TI  - Automated electrochemical free radical scavenger screening in dietary samples.
AB  - An automated electrochemical microtiter plate assay for the quantification of
      free radical scavengers (antioxidants) in food samples is described. Dietary
      antioxidant capacity measurements were achieved using the radical compound 2,2
      diphenyl-1-picrylhydrazyl (DPPH.) as an amperometric redox indicator, with a
      pencil lead working electrode, in conjunction with a Pt counter-electrode and
      Ag/AgCl reference electrode, moving sequentially through the 24 vials of a
      standard 6 * 4 microtiter plate. Programmed analyses were performed successfully
      with synthetic antioxidants of known concentrations and with tea infusions, fruit
      juices, and vegetable extracts. The novel methodology is simple and convenient
      as, unlike common DPPH. antioxidant electroanalysis, it avoids the time-consuming
      cleaning of electrochemical cells between measurements. Microtiter plate-based
      robotic electrochemical antioxidant assaying is thus a good option for handling
      large sample collections and may be applicable in the production of food and
      herbal remedies.

PMID- 22881403
TI  - Update on acute endovascular and surgical stroke treatment.
AB  - Emergency stroke care has become a natural part of the emerging discipline of
      neurocritical care and demands close cooperation between the neurologist and
      neurointerventionists, neurosurgeons, and anesthesiologists. Endovascular
      treatment (EVT), including intra-arterial thrombolysis, mechanical thrombectomy
      and angioplasty/stenting, is under rapid development. Although EVT has yet to be
      shown in randomized controlled trials to improve clinical outcome compared to
      intravenous thrombolysis, it is far better in achieving recanalization of
      occluded large cerebral vessels, which is crucial for rescuing the penumbra.
      Moreover, decompressive craniectomy is now a well-established treatment option
      for malignant middle cerebral artery infarction and cerebellar stroke. Using a
      case-based approach, this article reviews recent achievements in advanced
      treatment options for patients with acute ischemic stroke.

PMID- 22881404
TI  - New approach for the surface enhanced resonance Raman scattering (SERRS)
      detection of dopamine at picomolar (pM) levels in the presence of ascorbic acid.
AB  - The development of a novel surface-enhanced resonance Raman scattering (SERRS)
      platform that allows fast and sensitive detection of dopamine (DA) has been
      reported. The iron-nitrilotriacetic acid attached silver nanoparticle (Ag
      Fe(NTA)) substrate provides remarkable sensitivity and reliable repeatability.
      The advantages of both the surface functionalization for specific analytes and
      the SERRS are integrated into a single functional unit. While the silver core
      gives the necessary enhancing properties, the Fe-NTA receptors can trap DA
      adjacent the silver core and the NTA-Fe-DA complex formed provides resonance
      enhancement with a 632.8 nm laser. DA could be detected in pM level without any
      pretreatment with a reliable discrimination against AA, by utilizing low laser
      power (10 mW) and short data acquisition time (10 s). The high sensitivity along
      with the improved selectivity of this sensing approach is a significant step
      toward molecular diagnosis of Parkinson's disease.

PMID- 22881405
TI  - Mechanical stress-induced interleukin-1beta expression through adenosine
      triphosphate/P2X7 receptor activation in human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Mechanical stress is an important factor in maintaining
      homeostasis of the periodontium. Interleukin-1beta (IL-1beta) and adenosine
      triphosphate (ATP) are considered potent inflammatory mediators. In macrophages,
      ATP-activated P2X7 receptor is involved in IL-1beta processing and release. Our
      previous works demonstrated mechanical stress-induced expression of osteopontin
      and RANKL through the ATP/P2Y1 receptor in human periodontal ligament (HPDL)
      cells. This study was designed to examine the effect of mechanical stress on IL
      1beta expression in HPDL cells, as well as the mechanism and involvement of ATP
      and the P2 purinergic receptor. MATERIAL AND METHODS: Cultured HPDL cells were
      treated with continuous compressive loading. IL-1beta expression was analyzed at
      both mRNA and protein levels, using RT-PCR and ELISA, respectively. Cell
      viability was examined using the MTT assay. ATP was also used to stimulate HPDL
      cells. Inhibitors, antagonists and the small interfering RNA (siRNA) technique
      were used to investigate the role of ATP and the specific P2 subtypes responsible
      for IL-1beta induction along with the intracellular mechanism. RESULTS:
      Mechanical stress could up-regulate IL-1beta expression through the release of
      ATP in HPDL cells. ATP alone was also capable of increasing IL-1beta expression.
      The induction of IL-1beta was markedly inhibited by inhibitors and by siRNA
      targeting the P2X7 receptor. ATP-stimulated IL-1beta expression was also
      diminished by intracellular calcium inhibitors. CONCLUSION: Our work clearly
      indicates the capability of HPDL cells to respond directly to mechanical
      stimulation. The results signified the important roles of ATP/P2 purinergic
      receptors, as well as intracellular calcium signaling, in mechanical stress
      induced inflammation via up-regulation of the proinflammatory cytokine, IL-1beta,
      in HPDL cells.

PMID- 22881406
TI  - Pregnancy and birth outcomes of women with intellectual disability in Sweden: a
      national register study.
AB  - OBJECTIVE: To investigate the antenatal health and demographic factors as well as
      pregnancy and delivery outcomes in women with intellectual disability (ID) in
      Sweden. DESIGN: A population-based register study. SETTING: The National Patient
      Register (NPR) linked to the Medical Birth Register (MBR). SAMPLE: Women with ID
      classified as International Classification of Diseases (ICD) 8-10 who gave birth
      in 1999-2007 (n = 326), identified from the NPR linked to the MBR, were compared
      with all first-time, singleton mothers without ID or any other psychiatric
      diagnoses during this period in Sweden (n = 340 624). METHODS: Population-based
      data were extracted from the NPR and the MBR. MAIN OUTCOME MEASURES: Health and
      socio-demography at first antenatal visit, mode of delivery, pain relief during
      labor, preterm birth and discharge from hospital. RESULTS: A higher proportion of
      women with ID were teenagers (18.4 vs. 3.3%), obese (20.1 vs. 8.6%) and single
      (36.6 vs. 6.2%) compared with women without ID, and women with ID smoked more
      often (27.9 vs. 7.9%). Women with ID had more often a preterm birth (12.2 vs.
      6.1%), a cesarean section (CS) (24.5 vs. 17.7%) and used less nitrous oxide as
      pain relief during labor (59.5 vs. 75.8%). Women with ID had a higher risk for
      preterm birth [odds ratio (OR) 1.68], CS (OR1.55), non-use of nitrous oxide (OR
      1.89) and discharge from hospital to a place other than home (OR 2.24).
      CONCLUSION: Pregnant women with ID should be considered a risk group suggesting
      that better tailored pre- and intrapartum care and support are needed for these
      women.

PMID- 22881407
TI  - Analysis of secondary phenotype involving the interactive effect of the secondary
      phenotype and genetic variants on the primary disease.
AB  - A genome-wide association (GWA) study is usually designed as a case-control
      study, where the presence and absence of the primary disease define the cases and
      controls, respectively. Using the existing data from GWA studies, investigators
      are also trying to identify the association between genetic variants and
      secondary phenotypes, which are defined as traits associated with the primary
      disease. However, recent studies have shown that bias arises in the estimation of
      marker-secondary phenotype association using originally collected data. We
      recently proposed a bias correction approach to accurately estimate the odds
      ratio (OR) for marker-secondary phenotype association. In this communication, we
      further investigated whether our bias correction approach is robust for a
      scenario involving the interactive effect of the secondary phenotype and genetic
      variants on the primary disease. We found that in such a scenario, our bias
      correction approach also provides an accurate estimation of OR for marker
      secondary phenotype association. We investigated accuracy of our approach using
      simulation studies and showed that the approach better controlled for type I
      errors than the existing approaches. We also applied our bias correction approach
      to the real data analysis of association between an N-acetyltransferase gene,
      NAT2, and smoking on the basis of colorectal adenoma data.

PMID- 22881408
TI  - Impact of particulate antigens, such as Bacillus anthracis, on the uniformity of
      response across a biosensor flow cell as determined by GC-SPR.
AB  - Biosensors are desired for the detection of a wide range of analytes in various
      scenarios, for example environmental monitoring for biological threats, from
      toxins to viruses and bacteria. Ideally a single sensor will be capable of
      simultaneous multianalyte detection. The varying nature, and in particular
      disparate size, of such a variety of analytes poses a significant challenge in
      the development of effective high-confidence instruments. Many existing
      biosensors employ functionalized flow cells in which spatially defined arrays of
      surface-immobilized recognition elements, such as antibodies, specifically
      capture their analyte of interest. To function optimally, arrays should provide
      equivalent responses for equivalent events across their active area. Experimental
      data obtained using a grating coupled surface plasmon resonance (GC-SPR)
      instrument, the BIAcore Flexchip, have revealed differences in response behaviors
      between proteinaceous and particulate analytes. In particular, the magnitude of
      responses seen with Bacillus anthracis spores appears to be influenced by shear
      and gravitational effects while those from soluble proteins are more uniform. We
      have explored this dependence to understand its fundamental impact on the
      successful implementation of multianalyte environmental biological detection
      systems.

PMID- 22881409
TI  - Necrosis of uninvolved bone marrow following filgrastim administration in a
      patient with Burkitt lymphoma undergoing chemotherapy.

PMID- 22881410
TI  - alpha-Oxo-gamma-butyrolactam, N-containing pronucleophile in organocatalytic one
      pot assembly of butyrolactam-fused indoloquinolizidines.
AB  - The ambident reactivity of alpha-oxo-gamma-butyrolactam has been explored in an
      organocatalytic one-pot Michael/Pictet-Spengler sequence. The synthetically
      interesting and medicinally important pentacyclic butyrolactam-fused
      indoloquinolizidines can be efficiently constructed in a highly stereocontrolled
      manner. Importantly, the chemistry described herein provides a general catalytic
      method for the enantioselective synthesis of butyrolactam-incorporated chemical
      entities.

PMID- 22881411
TI  - The impact of active coping strategies on survival in ALS: the first pilot study.
AB  - The aim of this study was to examine the coping strategies of 49 patients with
      amyotrophic lateral sclerosis (ALS) and the potential impact of these strategies
      on survival. A total of 49 subjects were recruited. Each subject was asked to
      complete a questionnaire on coping strategies called the Brief COPE. The various
      coping strategies were divided into three factor sets through a factorial
      analysis: active coping (alpha 0.84), social support (alpha 0.71) and avoidance
      (alpha 0.71). Each score was divided into two subgroups in relation to the median
      (limited use vs. frequent use). Equality of survival distributions for the
      different levels of coping strategies was estimated using the Kaplan-Meier (Log
      Rank (Mantel-Cox)) model, with adjustment for mental health (GHQ-28), disease
      severity (ALSFRS), clinical form at onset (bulbar vs. spinal), medical assistance
      (ventilation and gastrostomy), participation in a clinical trial and gender.
      Results revealed a significant and positive impact of active coping strategies
      while taking mental health, ALSFRS scores, clinical form at onset, medical
      assistance, participation in a clinical trial and gender into account (Log Rank
      (Mantel-Cox) p < 0.05). Our study clearly demonstrates the impact of active
      coping strategies on survival in ALS.

PMID- 22881412
TI  - Involvement of spinal sensory pathway in ALS and specificity of cord atrophy to
      lower motor neuron degeneration.
AB  - Our objective was to demonstrate that ALS patients have sensory pathway
      involvement and that local cord atrophy reflects segmental lower motor neuron
      involvement. Twenty-nine ALS patients with spinal onset and twenty-one healthy
      controls were recruited. Diffusion tensor imaging (DTI), magnetization transfer
      and atrophy index were measured in the spinal cord, complemented with
      transcranial magnetic stimulations. Metrics were quantified within the lateral
      corticospinal and the dorsal segments of the cervical cord. Significant
      differences were detected between patients and controls for DTI and magnetization
      transfer metrics in the lateral and dorsal segments of the spinal cord.
      Fractional anisotropy correlated with ALSFRS-R (p = 0.04) and motor threshold (p
      = 0.02). Stepwise linear regression detected local spinal cord atrophy associated
      with weakness in the corresponding muscle territory, i.e. C4 level for deltoid
      and C7 level for hand muscles. In conclusion, impairment of spinal sensory
      pathways was detected at an early stage of the disease. Our data also demonstrate
      an association between muscle deficits and local spinal cord atrophy, suggesting
      that atrophy is a sensitive biomarker for lower motor neurons degeneration.

PMID- 22881413
TI  - Pathogenesis of infantile hemangiomas.
AB  - 1.Review the key features of the life cycle of infantile hemangiomas.2.Highlight
      cellular and molecular pathways involved in hemangioma-genesis.3.Discuss theories
      that may account for hemangioma-genesis.In the past, it was believed that a
      mother's visual impressions or behavior during pregnancy caused the growth of
      infantile hemangioma in her unborn child. She might have had an excessive craving
      for strawberries, witnessed the slaughter of an animal, directly contacted human
      or animal blood, or mocked a child with a similar birthmark.1 This folklore began
      to slowly fade once hemangiomas were examined through the light microscope. In
      1863, Virchow2 suggested that hemangiomas are composed of proliferating new blood
      vessels resulting from progressive irritation of tissue. In 1933, Laidlow and
      Murray3 proposed a phylogenetic origin for hemangiomas and hypothesized that
      hemangiomas are remnants of vascular tufts functioning as accessory lungs for
      primitive amphibia. Pack and Miller4 (1950) hypothesized that hemangiomas develop
      from embryonic islands of angioblastic cells that were isolated from the systemic
      vasculature during fetal development.

PMID- 22881414
TI  - Differential diagnosis of infantile hemangiomas.
AB  - 1.Compare and contrast infantile hemangiomas with other vascular anomalies that
      may be confused clinically.2.Describe the vascular anomalies classification
      system according to the International Society for the Study of Vascular Anomalies
      (ISSVA), highlighting the differences between vascular tumors, such as infantile
      hemangiomas, and vascular malformations.3.Briefly review associated signs or
      syndromes found in the context of certain vascular anomalies.Infantile
      hemangiomas are the most common benign vascular tumor in infancy but may mimic
      many other types of vascular anomalies. In many cases, the appearance, time of
      onset, growth pattern, and consistency of infantile hemangiomas make the
      diagnosis straightforward (see "Pathogenesis of Infantile Hemangiomas" on p.
      321). However, many other vascular lesions can appear quite similar to infantile
      hemangiomas, especially early in life, and at times this makes the correct
      diagnosis challenging.

PMID- 22881415
TI  - Treatment of infantile hemangiomas.
AB  - 1.Recognize infantile hemangiomas that are associated with a higher risk for
      complications and associated anomalies.2.Appreciate the typical timing of growth
      and involution of infantile hemangiomas.3.Become familiar with recently reported
      treatments for infantile hemangiomas.Infantile hemangiomas are common
      proliferations of endothelial tissue that affect approximately 4% to 5% of
      infants.1 Lesions represent a broad clinical spectrum and their management has to
      be individualized. Fortunately, most infantile hemangiomas do not require active
      therapy and may be managed with "active nonintervention";2 however, it is
      important to recognize those that do require therapeutic intervention and to be
      familiar with the therapeutic options.

PMID- 22881416
TI  - Protect the children.

PMID- 22881418
TI  - Strength training safety for younger children.

PMID- 22881419
TI  - A 2-year-old girl with a finger injury and ingrown toenail.

PMID- 22881420
TI  - Etiologic and therapeutic pitfalls of newborn conjunctivitis.

PMID- 22881421
TI  - An 11-month-old boy with widespread itchy, crusted, and weeping plaques.

PMID- 22881422
TI  - Infantile hemangiomas: new frontiers.

PMID- 22881423
TI  - Choosing the right pediatric career path.

PMID- 22881424
TI  - Pediatric palliative pain and symptom management.

PMID- 22881425
TI  - Avoidance of burnout in the young athlete.

PMID- 22881426
TI  - A conversation with Samuel L. Katz, MD. Interviewed by Stanford T. Shulman.

PMID- 22881427
TI  - Enhanced cartilage formation via three-dimensional cell engineering of human
      adipose-derived stem cells.
AB  - Autologous chondrocyte implantation is an effective treatment for damaged
      articular cartilage. However, this method involves surgical procedures that may
      cause further cartilage degeneration, and in vitro expansion of chondrocytes can
      result in dedifferentiation. Adipose-derived stem cells (ADSCs) may be an
      alternative autologous cell source for cartilage regeneration. In this study, we
      developed an effective method for large-scale in vitro chondrogenic
      differentiation, which is the procedure that would be required for clinical
      applications, and the subsequent in vivo cartilage formation of human ADSCs
      (hADSCs). The spheroid formation and chondrogenic differentiation of hADSCs were
      induced on a large scale by culturing hADSCs in three-dimensional suspension
      bioreactors (spinner flasks). In vitro chondrogenic differentiation of hADSCs was
      enhanced by a spheroid culture compared with a monolayer culture. The enhanced
      chondrogenesis was probably attributable to hypoxia-related cascades and enhanced
      cell-cell interactions in hADSC spheroids. On hADSCs loading in fibrin gel and
      transplantation into subcutaneous space of athymic mice for 4 weeks, the in vivo
      cartilage formation was enhanced by the transplantation of spheroid-cultured
      hADSCs compared with that of monolayer-cultured hADSCs. This study shows that the
      spheroid culture may be an effective method for large-scale in vitro chondrogenic
      differentiation of hADSCs and subsequent in vivo cartilage formation.

PMID- 22881428
TI  - Functional-group specific aptamers indirectly recognizing compounds with alkyl
      amino group.
AB  - Aptamers are usually generated against a specific molecule. Their high
      selectivity makes them only suitable for studying specific targets. Since it is
      nearly impossible to generate aptamers for every molecule, it can be of great
      interest to select aptamers recognizing a common feature of a group of molecules
      in many applications. In this paper, we describe the selection of aptamers for
      indirect recognition of alkyl amino groups. Because amino groups are small and
      positive charged, we introduced a protection group, p-nitrobenzene sulfonyl (p
      nosyl) to convert them into a form suitable for aptamer selection. Taking
      N(epsilon)-p-nosyl-L-lysine (PSL) as a target, we obtained a group of aptamers
      using the SELEX technique. Two optimized aptamers, M6b-M14 and M13a exhibit
      strong affinity to PSL with the K(d) values in the range of 2-5 MUM. They also
      show strong affinity to other compounds containing p-nosyl-protected amino groups
      except those also possessing an alpha-carboxyl group. Both aptamers adopt an
      antiparallel G-quadruplex structure when binding to targets. An aptamer beacon
      based on M6b-M14 showed good selectivity toward the reaction mixture of p-nosyl
      Cl and alkyl amino compounds, and could recognize lysine from amino acid mixtures
      indirectly, suggesting that aptamers against a common moiety of a certain type of
      molecules can potentially lead to many new applications. Through this study, we
      have demonstrated the ability to select aptamers for a specific part of an
      organic compound, and the chemical conversion approach may prove to be valuable
      for aptamer selection against molecules that are generally difficult for SELEX.

PMID- 22881430
TI  - An efficient total synthesis of ruprechstyril from Ruprechtia tangarana.
AB  - A short total synthesis of natural isocarbostyril ruprechstyril (3-n-pentyl-6
      methoxy-8-hydroxy-1(2H)-isoquinolinone) isolated from Ruprechtia tangarana is
      reported. 6,8-Dimethoxy-3-pentylisocoumarin obtained by condensation of 3,5
      dimethoxyhomophthalic anhydride with hexanoyl chloride was smoothly converted to
      O-methylruprechstyril by refluxing with methanamide. Regioselective demethylation
      of the latter using anhydrous aluminium chloride in dichloromethane furnished the
      ruprechstyril. Complete demethylation to give (6-desmethoxyruprechstyril) was
      achieved using same reagent in ethanethiol. 

PMID- 22881429
TI  - The effect of a Beare-Stevenson syndrome Fgfr2 Y394C mutation on early
      craniofacial bone volume and relative bone mineral density in mice.
AB  - Quantifying the craniofacial skeletal phenotype during development highlights
      potential effects of known mutations on bone maturation and is an informative
      first step for the analysis of animal models. We introduce a novel technique to
      easily and efficiently quantify individual cranial bone volume and relative bone
      mineral density across the murine skull from high resolution computed tomography
      images. The approach can be combined with existing quantitative morphometric
      methods to provide details of bone growth and bone quality, which can be used to
      make inferences about regulatory effects local to individual bones and identify
      locations and developmental times for which additional analyses are warranted.
      Analysis of the Fgfr2(+/Y394C)  mouse model of Beare-Stevenson cutis gyrata
      syndrome, an FGFR-related craniosynostosis syndrome, is used to demonstrate the
      method. Mutants and unaffected littermates display similar bone volume and
      relative bone density at birth, followed by significant differences at postnatal
      day eight. The change in rates of bone volume growth occurs similarly for all
      bones of the skull, regardless of origin, location or association with
      craniosynostosis. These results suggest an association between low bone density,
      low bone volume, and Fgfr craniosynostosis mutations. Our novel technique
      provides an initial quantitative evaluation of local shifts in bone maturation
      across the skull of animal models.

PMID- 22881431
TI  - Crystallization and preliminary X-ray analysis of membrane-bound
      pyrophosphatases.
AB  - Membrane-bound pyrophosphatases (M-PPases) are enzymes that enhance the survival
      of plants, protozoans and prokaryotes in energy constraining stress conditions.
      These proteins use pyrophosphate, a waste product of cellular metabolism, as an
      energy source for sodium or proton pumping. To study the structure and function
      of these enzymes we have crystallized two membrane-bound pyrophosphatases
      recombinantly produced in Saccharomyces cerevisae: the sodium pumping enzyme of
      Thermotoga maritima (TmPPase) and the proton pumping enzyme of Pyrobaculum
      aerophilum (PaPPase). Extensive crystal optimization has allowed us to grow
      crystals of TmPPase that diffract to a resolution of 2.6 A. The decisive step in
      this optimization was in-column detergent exchange during the two-step
      purification procedure. Dodecyl maltoside was used for high temperature
      solubilization of TmPPase and then exchanged to a series of different detergents.
      After extensive screening, the new detergent, octyl glucose neopentyl glycol, was
      found to be the optimal for TmPPase but not PaPPase.

PMID- 22881432
TI  - Association of three different techniques to measure blood pressure in the first
      trimester with the development of hypertensive disorders of pregnancy.
AB  - OBJECTIVE: It is not known whether automated devices for measuring blood pressure
      perform better than conventional sphygmomanometry in predicting preeclampsia.
      This study compares two different automated devices with conventional
      sphygmomanometry for their association with development of preeclampsia or
      gestational hypertension. DESIGN: Prospective observational cohort study.
      SETTING: University hospital, Amsterdam, the Netherlands. POPULATION: 289 healthy
      normotensive women of whom 235 were nulliparous and 44 parous with preeclampsia
      in a previous pregnancy. METHODS: At 8-11 weeks of pregnancy, blood pressure was
      measured with two different automated devices (continuous finger arterial
      pressure waveform registration and ambulatory blood pressure monitoring) and with
      conventional sphygmomanometry. MAIN OUTCOME MEASURES: Preeclampsia and
      gestational hypertension. RESULTS: Blood pressure in the first trimester, as
      measured with all three methods, was significantly higher in women who developed
      preeclampsia or gestational hypertension. After adjustment for previous
      preeclampsia, the point estimate of the odds ratios for association with later
      preeclampsia for both automated devices were comparable and higher than for
      conventional sphygmomanometry; however, differences were not statistically
      significant. The odds ratio (95% confidence intervals) for every 1 mmHg pressure
      increase of mean arterial pressure was 1.08 (1.02-1.15) for sphygmomanometry,
      1.17 (1.09-1.27) for finger arterial pressure waveform registration, and 1.17
      (1.07-1.27) for ambulatory blood pressure monitoring. Results were comparable if
      preeclampsia and gestational hypertension were analyzed together. CONCLUSION:
      Blood pressure in the first trimester was associated with the development of
      hypertensive disorders of pregnancy. No significant differences were found
      between measurements by automatic devices compared with conventional
      sphygmomanometry.

PMID- 22881433
TI  - Themed issue: Inhalation pharmaceutics--current technologies and approaches to
      respiratory drug delivery.

PMID- 22881434
TI  - Twenty years of HFA pMDI patents: facts and perspectives.
AB  - OBJECTIVES:  Over the past 20 years, the inhalation drug delivery industry has
      undergone a quiet revolution after the phasing out of the chlorofluorocarbon
      propellants used to formulate pressure-metered dose inhalers (pMDIs). This review
      looks back to the creative landscape of those 20 years through a study of patent
      application trends. To this end, an analysis of the hydrofluoroalkane pMDIs
      patent landscape was undertaken. METHODS: A statistical analysis demonstrates
      that 20 years after the introduction of hydrofluoroalkanes in the inhalation
      delivery field, the original patent applications are coming to the end of their
      legal life. KEY FINDINGS: Detailed analysis revealed that, from a total of 971 of
      the patents identified, up to 2.3% will expire within the next 5 years, rising to
      up to 7.3% in the next 10 years. The UK and USA were the main patent destinations
      and locations of inventive activity, as measured by patent filing location.
      Interestingly, the UK was the first destination and location of inventive
      activity in Europe, largely due to the activity of GlaxoSmithKline, followed by
      Italy, thanks to the work of Trinity-Chiesi. The analysis also showed that patent
      assignees are not always major pharmaceutical companies, with suppliers of
      propellants, as well as companies without major inhalation activity (such as
      Novadel), making substantial contributions to the landscape. CONCLUSIONS: These
      developments may have a significant impact on innovation trends and key company
      activity around novel pMDI formulations, in particular for generics
      manufacturers.

PMID- 22881435
TI  - Engineered PLGA nano- and micro-carriers for pulmonary delivery: challenges and
      promises.
AB  - OBJECTIVES: The aim of this review is to summarize the current state-of-the-art
      in poly(lactic-co-glycolic acid) (PLGA) carriers for inhalation. It presents the
      rational of use, the potential and the recent advances in developing PLGA
      microparticles and nanoparticles for pulmonary delivery. The most promising
      particle engineering strategies are discussed, highlighting the advantages along
      with the major challenges for researchers working in this field. KEY FINDINGS:
      Biodegradable polymer carriers, such as PLGA particles, may permit effective
      protection and long-term delivery of the inhaled drug and, when adequately
      engineered, its efficient transport to the target. The carrier can be designed
      for inhalation on the basis of several strategies through the adequate
      combination of available particle technologies and excipients. In so doing, the
      properties of PLGA particles can be finely tuned at micro-size and nano-size
      level to fulfill specific therapeutic needs. This means not only to realize
      optimal in vitro/in vivo lung deposition of the formulation, which is still
      crucial, but also to control the fate of the drug in the lung after particle
      landing. SUMMARY: Although many challenges still exist, PLGA carriers may be
      highly beneficial and present a new scenario for patients suffering from chronic
      lung diseases and for pharmaceutical companies working to develop novel inhaled
      products.

PMID- 22881436
TI  - Solvation in hydrofluoroalkanes: How can ethanol help?
AB  - OBJECTIVES: The goal of this work was to evaluate the ability of ethanol mixed
      with hydrofluoroalkanes (HFAs) to improve solvation of moieties of relevance to
      pressurized metered-dose inhalers (pMDIs). METHODS: Chemical force microscopy was
      used to measure the adhesion force (F(ad)) between alkyl-based, ether-based and
      ester-based moieties (C8/C8, COC/COC and COOC/COOC interactions) in 2H,3H
      perfluoropentane (HPFP)/ethanol mixtures. HPFP is a liquid that mimics propellant
      HFAs. The F(ad) results are thus a measure of solvation in HFAs. Johnson-Kendall
      Roberts (JKR) theory was used to model the results. KEY FINDINGS: The F(ad)
      normalized by the tip radius of curvature (F(ad)/R) decreased upon the addition
      of ethanol, suggesting its ability to enhance the solvent environment. At 15%
      (v/v) ethanol, the F(ad)/R was reduced 34% for the alkyl, 63% for the ether, and
      down 67% for the ester tails. Thus, the solvation could be ranked as: ester >
      ether > alkyl. JKR theory was a reasonable model for the F(ad)/R. CONCLUSIONS:
      Ethanol, within the concentration range of interest in commercial pMDIs, provided
      limited enhancement in solvation of alkyl moieties. On the other hand, the
      cosolvent significantly enhanced solvation of ether-based and ester-based
      moieties, thus suggesting its potential for formulations containing amphiphiles
      with such groups.

PMID- 22881437
TI  - Co-deposition of a triple therapy drug formulation for the treatment of chronic
      obstructive pulmonary disease using solution-based pressurised metered dose
      inhalers.
AB  - OBJECTIVES: The formulation of multi-drug pressurised metered dose inhalers
      (pMDIs) opens up exciting therapeutic opportunities for the treatment of asthma
      and chronic obstructive pulmonary disease (COPD). We have investigated the
      formulation of a solution-based triple therapy pMDI containing ipratropium,
      formoterol, budesonide and ethanol as co-solvent. METHODS: This system was
      characterised for in-vitro performance and compared with marketed pMDIs (Atrovent
      and Symbicort). KEY FINDINGS: No significant difference was found in the stage
      deposition of each drug from the triple therapy formulation, suggesting that the
      droplets contained a fixed ratio of the three components used. Stage deposition
      of formoterol and budesonide from the suspension-based marketed Symbicort were
      significantly different, suggesting that the two drugs were deposited as separate
      entities. Calculation of the mass median aerodynamic diameter (MMAD) of each
      formulation suggested Atrovent (ipratropium, MMAD = 0.9 +/- 0.0 um) to have a
      small particle size, similar to the triple therapy formulation. Atrovent, like
      the triple therapy formulation was solution based and it contained ethanol as a
      co-solvent (triple therapy formulation, MMAD = 1.3 +/- 0.0 um). CONCLUSIONS: This
      study demonstrated the feasibility of formulating a solution-based pMDI
      containing a triple therapy with identical deposition pattern for the treatment
      of several respiratory diseases where multi-drug cell targeting is required.

PMID- 22881438
TI  - Condensational growth of combination drug-excipient submicrometer particles for
      targeted high-efficiency pulmonary delivery: evaluation of formulation and
      delivery device.
AB  - OBJECTIVES: The objective of this study was to investigate the in-vitro particle
      size growth of combination drug and excipient submicrometer aerosols generated
      from a series of formulations and two aerosol delivery devices. METHODS:
      Submicrometer combination drug and excipient particles were generated
      experimentally using both the capillary aerosol generator and the Respimat
      inhaler. Budesonide and albuterol sulfate were used as model drugs and were
      formulated with sodium chloride, citric acid and mannitol as excipients in
      various ratios. Aerosol growth was evaluated in-vitro in a coiled-tube geometry
      designed to provide residence times and thermodynamic conditions consistent with
      the airways. KEY FINDINGS: Submicrometer combination drug : excipient aerosols
      when exposed to simulated respiratory conditions increased to micrometer size
      suitable for pulmonary deposition. It was possible to control the aerosol growth
      ratio by altering: (1) the hygroscopic excipient, (2) the drug : excipient ratio
      and (3) the drug. The applicability of this approach was demonstrated using the
      capillary aerosol generator and the Respimat inhaler. CONCLUSIONS: The enhanced
      excipient growth approach may enable the delivery of submicrometer aerosol
      particles that increase in size within the airways and result in high percentages
      of pulmonary deposition.

PMID- 22881439
TI  - Preparation and characterisation of novel spray-dried nano-structured para
      aminosalicylic acid particulates for pulmonary delivery: impact of ammonium
      carbonate on morphology, chemical composition and solid state.
AB  - OBJECTIVES: The objective of this work was to spray dry p-aminosalicylic acid
      (PAS) and its ammonium salt and to investigate the impact of the pore-forming
      agent, ammonium carbonate (AC), on the morphological, aerodynamic and
      physicochemical properties of the resulting powders. METHODS: Microparticles were
      prepared by spray drying from ethanol/water solvent systems. Their solid-state
      properties were evaluated by scanning electron microscopy, powder X-ray
      diffraction, differential scanning calorimetry, thermogravimetric analysis and in
      vitro deposition, using the twin impinger. KEY FINDINGS: The physicochemical
      properties of PAS were altered on spray drying with AC and a new solid state was
      produced. The solution composition impacted on the morphology of the resulting
      powders, which ranged from irregular crystal agglomerates to spherical crystal
      clusters and porous microparticles. The chemical composition, structure and
      morphology were dependent on process inlet temperature, low inlet temperatures
      resulting in a novel solid of stoichiometry; PAS : ammonia : water, 2 : 1 : 0.5.
      At higher temperatures pure PAS was obtained. In-vitro deposition studies showed
      an increase in emitted dose from spray dried drug, relative to the micronised
      PAS. CONCLUSIONS: Under appropriate process conditions AC interacts with the
      acidic PAS, resulting in the formation of a novel solid-state drug phase. Spray
      dried PAS powders have potential for pulmonary delivery.

PMID- 22881440
TI  - Spray drying from organic solvents to prepare nanoporous/nanoparticulate
      microparticles of protein: excipient composites designed for oral inhalation.
AB  - OBJECTIVES: The aim of this study was to determine if spray-drying could
      successfully produce microparticles containing the model protein trypsin in a
      form suitable for inhalation. METHODS: Trypsin was spray-dried with raffinose
      from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system
      was then adjusted to include water, and trypsin was co-spray-dried with
      raffinose, trehalose or hydroxpropyl-beta-cyclodextrin. The spray-dried products
      were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity
      and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate
      microparticles (NPMPs) was also assessed. KEY FINDINGS: The inclusion of water in
      a MeOH : BA solvent system allowed for the successful production of NPMPs of
      trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient
      NPMPs retained biological activity on processing and showed no deterioration in
      activity or morphological characteristics when stored with desiccant at either 4
      or 25 degrees C. Hydroxpropyl-beta-cyclodextrin showed advantages over the sugars
      in terms of producing powders with appropriate density and with greater physical
      stability under high-humidity conditions. Fine particle fractions of between 41
      and 45% were determined for trypsin : excipient NPMPs. CONCLUSIONS: NPMPs of
      trypsin : excipient systems can be produced by spray-drying by adjustment of the
      solvent system to allow for adequate solubility of trypsin.

PMID- 22881441
TI  - Preparation of sustained release rifampicin microparticles for inhalation.
AB  - OBJECTIVES: The aim of this research was to develop a novel carrier-free dry
      powder formulation of rifampicin for inhalation with controlled-release
      properties. METHODS: Rifampicin dihydrate (RFDH) microcrystals were prepared by a
      polymorphic transformation of rifampicin. The prepared RFDH microcrystals were
      coated with poly (DL-lactide-co-glycolide) or poly (DL-lactide), using a spray
      dryer equipped with two different types of three-fluid (3F) spray nozzles. The
      physicochemical and aerodynamic properties of the coated RFDH microcrystals were
      compared with those of conventional matrix microparticles. KEY FINDINGS: The
      coated RFDH powder, encapsulating 50% of rifampicin, was successfully prepared by
      simple in-situ coating methods using two different types of 3F nozzles and had
      mass median aerodynamic diameter values of 3.5-4.5 uM. The thin flaky morphology
      of RFDH powders, providing good aerosolization properties, was maintained after
      coating. The coated RFDH formulations showed relatively low initial rifampicin
      release, compared with the uncoated RFDH crystals, followed by slow rifampicin
      release (about 70%) over 8 h in phosphate-buffered saline media (pH 7.4).
      Significant chemical degradations were not observed from the crystalline
      structured RFDH formulations, while the amorphous-structured matrix formulations
      showed chemical degradation in six months. CONCLUSIONS: These polymer coated RFDH
      formulations may be a valuable alternative in the treatment of tuberculosis since
      the carrier-free formulation offers the benefit of delivering a maximum-potency
      formulation of the antibiotic directly to the site of infection, and long drug
      residence times may be achieved by the controlled release of the drug.

PMID- 22881442
TI  - Rational design of a dry powder inhaler: device design and optimisation.
AB  - OBJECTIVES: As part of the development of a dry powder inhalation system for the
      treatment of asthma and chronic obstructive pulmonary disease, this work
      specifically aimed at the systematic, however, cost-effective and efficient
      development of an inhalation device. METHODS: Based on theoretical design
      considerations and an initial inhaler prototype, the concept of a modular inhaler
      was developed. The modular inhaler was used for the systematic evaluation of the
      influence of the inhaler's inner dimensions on the resistance to the air flow and
      the in-vitro deposition characteristics of the inhalation system by using
      statistical design of experiments and cascade impaction analysis. KEY FINDINGS: A
      reliable statistical model enabled the accurate prediction of the device
      resistance of any combination of inner dimensions of the inhaler. In conjunction
      with results from in-vitro deposition studies, this allowed for the definition of
      optimised inner dimensions of the inhaler to maximise the fine particle fraction
      and minimise oropharyngeal deposition within the desired range of the inhaler's
      resistance to air flow. CONCLUSIONS: The concept of the modular inhaler and
      statistical design and evaluation of experiments proved to be important tools for
      an efficient and successful product development. Eventually, the approaches
      described and the knowledge obtained enabled the cost-effective development and
      design of a technically feasible and competitive dry powder inhaler.

PMID- 22881443
TI  - Computational fluid dynamics (CFD) assisted performance evaluation of the
      TwincerTM disposable high-dose dry powder inhaler.
AB  - OBJECTIVES: To use computational fluid dynamics (CFD) for evaluating and
      understanding the performance of the high-dose disposable TwincerTM dry powder
      inhaler, as well as to learn the effect of design modifications on dose
      entrainment, powder dispersion and retention behaviour. METHODS: Comparison of
      predicted flow and particle behaviour from CFD computations with experimental
      data obtained with cascade impactor and laser diffraction analysis. KEY FINDINGS:
      Inhaler resistance, flow split, particle trajectories and particle residence
      times can well be predicted with CFD for a multiple classifier based inhaler like
      the TwincerTM. CFD computations showed that the flow split of the TwincerTM is
      independent of the pressure drop across the inhaler and that the total flow rate
      can be decreased without affecting the dispersion efficacy or retention
      behaviour. They also showed that classifier symmetry can be improved by reducing
      the resistance of one of the classifier bypass channels, which for the current
      concept does not contribute to the swirl in the classifier chamber. CONCLUSIONS:
      CFD is a highly valuable tool for development and optimisation of dry powder
      inhalers. CFD can assist adapting the inhaler design to specific physico-chemical
      properties of the drug formulation with respect to dispersion and retention
      behaviour.

PMID- 22881444
TI  - Influence of crystal form of ipratropium bromide on micronisation and
      aerosolisation behaviour in dry powder inhaler formulations.
AB  - OBJECTIVES: This study aimed to investigate the relationship between the
      mechanical properties of anhydrous and monohydrate ipratropium bromide (IB)
      crystals, their processing behaviour upon air-jet micronisation and
      aerosolisation performance in dry powder inhaler (DPI) formulations. METHODS: IB
      monohydrate and anhydrous crystals were produced from seed crystals and
      supercritical carbon dioxide crystallisation, respectively. Young's modulus of
      anhydrous and monohydrate IB crystals was determined using nanoindentation. For
      air-jet micronised crystals, the physicochemical and surface interfacial
      properties via the cohesive-adhesive balance (CAB) approach were investigated.
      These data were correlated to in-vitro aerosolisation performance of carrier
      based DPI formulations containing either anhydrous or monohydrate IB. KEY
      FINDINGS: Particle size and Young's modulus of both crystals were similar and
      this was reflected in their similar processing upon micronisation. Particle size
      of micronised anhydrous and monohydrate crystals were similar. CAB measurements
      of the micronised particles of monohydrate or anhydrous forms of IB with respect
      to lactose were 0.70 (R2 = 0.998) and 0.77 (R2 = 0.999), respectively. These data
      suggested that both samples had similar adhesion to lactose, which correlated
      with their similar in-vitro aerosolisation performance in DPI formulations.
      CONCLUSIONS: Monohydrate and anhydrous crystals of IB exhibited similar
      mechanical properties and interfacial properties upon secondary processing. As a
      result, the performance of the DPI formulations were similar.

PMID- 22881445
TI  - Characterising surface energy of pharmaceutical powders by inverse gas
      chromatography at finite dilution.
AB  - OBJECTIVES: The objectives of this project were the use of surface energy
      distributions in: distinguishing the effects of magnesium stearate on the surface
      energy of lactose processed by two methods: mixing in a Turbula and
      mechanofusion; characterising surface energy of materials before and after
      micronisation; and understanding surface energy changes of micronised lactose
      before and after storage at high relative humidity (RH). METHODS: Heptane, octane
      and nonane were used to determine nonpolar surface energy, and dichloromethane
      and ethyl acetate were used to determine polar surface energy in inverse gas
      chromatography at finite dilution. KEY FINDINGS: The total surface energy of
      lactose decreased more after mechanofusion with magnesium stearate than mixing in
      Turbula. The nonpolar surface energy of indometacin increased while polar and
      total surface energies decreased after micronisation. The nonpolar, polar and
      total surface energies and work of cohesion of micronised lactose decreased after
      storage at 75% RH for three months. CONCLUSIONS: The surface energy distributions
      determined at finite dilution successfully distinguished and revealed more
      information than infinite dilution on surface energy changes in materials
      undergoing different pharmaceutical processes such as mixing, mechanofusion,
      micronisation and storage at high RH.

PMID- 22881446
TI  - Enhanced dissolution performance of curcumin with the use of supersaturatable
      formulations.
AB  - The goal of this research was to employ formulation strategies to develop
      supersaturatable formulations for curcumin, a poorly water-soluble drug to
      improve the in vitro dissolution performance. Self-emulsifying lipid-based
      formulations and hydrophilic carrier formulations with polymeric precipitation
      inhibitors were designed to achieve supersaturation upon dilution. In vitro
      dissolution of curcumin from each formulation was performed, in addition to
      assessment of the utility of polymers such as polyvinylpyrrolidone (PVP),
      hydroxypropyl methyl cellulose (HPMC) as precipitation inhibitors. For the
      hydrophilic solvent formulation, it was observed that the presence of 10% w/w
      polymer results in curcumin concentrations almost 100-fold greater compared to
      the formulation without the polymer. Incorporation of polymer in the SEDDS
      formulation results in a supersaturated solution of curcumin with concentrations
      identical to the theoretical starting dose. The high drug concentrations were
      sustained for 3 h as compared to the self-emulsifying formulation without the
      polymer. The low dissolution of curcumin in the neat hydrophilic solvent and self
      emulsifying formulation is attributed to the uncontrolled precipitation of the
      drug upon mixing with the dissolution media, which is a result of formation of an
      unstable supersaturated solution. Upon relative assessment, the rank order in
      which the polymers inhibited precipitation was PVP-K30 < PVP-K90 < HPMC.

PMID- 22881447
TI  - "Tight control" in geriatrics: the emperor wears a thong.
AB  - The deep-seated faith in tight glycemic control for patients with type 2 diabetes
      mellitus shows signs of moderating, especially for elderly adults, but faith in
      the importance of a glycosylated hemoglobin goal of 7% retains a strong influence
      over many clinicians. This faith persists despite weak evidence from randomized
      controlled trials of any meaningful benefit from "tight control" in any patient
      group, consistent evidence of lack of benefit for many outcomes, and an almost
      complete lack of evidence about elderly adults or those with extensive vascular
      disease. Clinicians who care for these vulnerable individuals face a strong
      public belief in "tight control" and an orchestrated campaign to increase
      medication use. Although no benefit has been shown in elderly adults, some harms
      are clear, and others are likely.

PMID- 22881448
TI  - Amyotrophic lateral sclerosis in Sardinia (Italy): epidemiologic features from
      1957 to 2000.
AB  - OBJECTIVES: To evaluate epidemiological variables of amyotrophic lateral
      sclerosis (ALS) in Sardinia (Italy) in the 1991-2000 periods and compare them
      with the preceding decades. MATERIAL AND METHODS: Survey, critical reappraisal or
      clinical re-evaluation of all ALS cases with onset in the decade 1991-2000;
      calculation of crude and age-adjusted incidence, duration of disease, survival
      rates and the latency between onset of symptoms and diagnosis. RESULTS: A
      significant increase in the mean annual incidence was observed in comparison with
      the values found in the two previous decades, 1971-1980 and 1981-1990. The
      distribution of the disease in various areas of the island was found to be not at
      all homogeneous. No significant modifications of the duration of the disease and
      survival rates were observed. CONCLUSION: The role of particular exogenous
      factors, albeit still unclear, can be invoked.

PMID- 22881449
TI  - Energy-dependent electron activated dissociation of metal-adducted permethylated
      oligosaccharides.
AB  - The effects of varying the electron energy and cationizing agents on electron
      activated dissociation (ExD) of metal-adducted oligosaccharides were explored,
      using permethylated maltoheptaose as the model system. Across the examined range
      of electron energy, the metal-adducted oligosaccharide exhibited several
      fragmentation processes, including electron capture dissociation (ECD) at low
      energies, hot-ECD at intermediate energies, and electronic excitation
      dissociation (EED) at high energies. The dissociation threshold depended on the
      metal charge carrier(s), whereas the types and sequence spans of product ions
      were influenced by the metal-oligosaccharide binding pattern. Theoretical
      modeling contributed insight into the metal-dependent behavior of carbohydrates
      during low-energy ECD. When ExD was applied to a permethylated high mannose N
      linked glycan, EED provided more structural information than either collision
      induced dissociation (CID) or low-energy ECD, thus demonstrating its potential
      for oligosaccharide linkage analysis.

PMID- 22881450
TI  - A significant role for nitrate and peroxide groups on indoor secondary organic
      aerosol.
AB  - This paper reports indoor secondary organic aerosol, SOA, composition based on
      the results from an improved model for indoor air chemistry. The model uses a
      detailed chemical mechanism that is near-explicit to describe the gas-phase
      degradation of relevant indoor VOC species. In addition, gas-to-particle
      partitioning is included for oxygenated products formed from the degradation of
      limonene, the most ubiquitous terpenoid species in the indoor environment. The
      detail inherent in the chemical mechanism permits the indoor SOA composition to
      be reported in greater detail than currently possible using experimental
      techniques. For typical indoor conditions in the suburban UK, SOA concentrations
      are ~1 MUg m(-3) and dominated by nitrated material (~85%), with smaller
      contributions from peroxide (12%), carbonyl (3%), and acidic (1%) material.
      During cleaning activities, SOA concentrations can reach 20 MUg m(-3) with the
      composition dominated by peroxide material (73%), with a smaller contribution
      from nitrated material (21%). The relative importance of these different moieties
      depends crucially (in order) on the outdoor concentration of O(3), the deposition
      rates employed and the scaling factor value applied to the partitioning
      coefficient. There are currently few studies that report observation of aerosol
      composition indoors, and most of these have been carried out under conditions
      that are not directly relevant. This study highlights the need to investigate SOA
      composition in real indoor environments. Further, there is a need to measure
      deposition rates for key indoor air species on relevant indoor surfaces and to
      reduce the uncertainties that still exist in gas-to-particle phase
      parametrization for both indoor and outdoor air chemistry models.

PMID- 22881451
TI  - Kinetics and mechanisms of the thermal decomposition of 2-methyl-1,3-dioxolane,
      2,2-dimethyl-1,3-dioxolane, and cyclopentanone ethylene ketal in the gas phase.
      Combined experimental and DFT study.
AB  - The kinetics of the gas-phase thermal decomposition of 2-methyl-1,3-dioxolane,
      2,2-dimethyl-1,3-dioxolane, and cyclopentanone ethylene ketal were determined in
      a static system and the reaction vessel deactivated with allyl bromide. The
      decomposition reactions, in the presence of the free radical suppressor propene,
      are homogeneous, are unimolecular, and follow first-order law kinetics. The
      products of these reactions are acetaldehyde and the corresponding ketone. The
      working temperature range was 459-490  degrees C, and the pressure range was 46
      113 Torr. The rate coefficients are given by the following Arrhenius equations:
      for 2-methyl-1,3-dioxolane, log k = (13.61 +/- 0.12) - (242.1 +/- 1.0)(2.303RT)(
      1), r = 0.9997; for 2,2-dimethyl-1,3-dioxolane, log k = (14.16 +/- 0.14) - (253.7
      +/- 2.0)(2.303RT)(-1), r = 0.9998; for cyclopentanone ethylene ketal, log k =
      (14.16 +/- 0.14) - (253.7 +/- 2.0)(2.303RT)(-1), r = 0.9998. Electronic structure
      calculations using DFT methods B3LYP and MPW1PW91 with 6-31G(d,p), and 6
      31++G(d,p) basis sets suggest that the decomposition of these substrates takes
      place through a stepwise mechanism. The rate-determining step proceeds through a
      concerted nonsynchronous four-centered cyclic transition state, and the
      elongation of the C-OCH(3) bond in the direction C(alpha)(delta+)...OCH(3)(delta
      ) is predominant. The intermediate products of these decompositions are unstable,
      at the working temperatures, decomposing rapidly through a concerted cyclic six
      centered cyclic transition state type of mechanism.

PMID- 22881452
TI  - Estimates of embodied global energy and air-emission intensities of Japanese
      products for building a Japanese input-output life cycle assessment database with
      a global system boundary.
AB  - To build a life cycle assessment (LCA) database of Japanese products embracing
      their global supply chains in a manner requiring lower time and labor burdens,
      this study estimates the intensity of embodied global environmental burden for
      commodities produced in Japan. The intensity of embodied global environmental
      burden is a measure of the environmental burden generated globally by unit
      production of the commodity and can be used as life cycle inventory data in LCA.
      The calculation employs an input-output LCA method with a global link input
      output model that defines a global system boundary grounded in a simplified
      multiregional input-output framework. As results, the intensities of embodied
      global environmental burden for 406 Japanese commodities are determined in terms
      of energy consumption, greenhouse-gas emissions (carbon dioxide, methane, nitrous
      oxide, perfluorocarbons, hydrofluorocarbons, sulfur hexafluoride, and their
      summation), and air-pollutant emissions (nitrogen oxide and sulfur oxide). The
      uncertainties in the intensities of embodied global environmental burden
      attributable to the simplified structure of the global link input-output model
      are quantified using Monte Carlo simulation. In addition, by analyzing the
      structure of the embodied global greenhouse-gas intensities we characterize
      Japanese commodities in the context of LCA embracing global supply chains.

PMID- 22881454
TI  - Re-evaluation of the proton affinity of 18-crown-6 using competitive threshold
      collision-induced dissociation techniques.
AB  - The proton affinity (PA) of 18-crown-6 (18C6) is determined using competitive
      threshold collision-induced dissociation (TCID) techniques. The PA of 18C6 is
      derived from four thermochemical cycles involving the relative thresholds for
      production of the protonated bases, H(+)(B), and protonated crown, H(+)(18C6),
      from the collision-induced dissociation (CID) of four proton bound heterodimers,
      (B)H(+)(18C6). The bases examined include glycine (Gly), alanine (Ala), imidazole
      (Imid), and 4-methylimidazole (4MeImid). In all cases, CID pathways for the loss
      of intact B and 18C6 are observed in competition. Loss of intact 18C6 is observed
      as the lowest-energy CID pathway for the (Imid)H(+)(18C6) and (4MeImid)H(+)(18C6)
      complexes. In contrast, loss of intact Gly and Ala is observed as the lowest
      energy CID pathway for the (Gly)H(+)(18C6) and (Ala)H(+)(18C6) complexes,
      respectively. Excellent agreement between the measured and calculated (B)H(+)
      18C6 and (18C6)H(+)-B bond dissociation energies (BDEs) is found with M06 theory,
      whereas B3LYP theory systematically underestimates these BDEs. On the basis of
      the relative TCID thresholds for the primary and competitive CID pathways, as
      well as the literature PAs of the bases, the PA of 18C6 is evaluated. The PA
      determined here for 18C6 exhibits excellent agreement with M06 and B3LYP
      theories, and very good agreement with the value reported by Meot-Ner determined
      using high pressure mass spectrometry (HPMS) techniques, suggesting that the PA
      of 18C6 reported in the NIST Webbook based on HPMS measurements by Kebarle and co
      workers is overestimated.

PMID- 22881453
TI  - A soluble copper(I) source and stable salts of volatile ligands for copper
      catalyzed C-X couplings.
AB  - A stable adduct of CuI with Bu(4)NI, soluble in organic solvents, has been
      identified as an effective catalyst for copper-catalyzed C-N and C-O couplings.
      In addition, stable nonhygroscopic salts of some high performance ligands
      (diamine MsOH salts/CuX and copper(II) diketonates) were shown to be of similar
      and sometimes greater reactivity compared to the literature reagents for these
      couplings. Furthermore, these more robust conditions result in more reproducible
      results.

PMID- 22881455
TI  - Guidelines on the investigation and management of venous thrombosis at unusual
      sites.

PMID- 22881456
TI  - Nanoinclusions in cryogenically quenched nanoemulsions.
AB  - Nanodroplets containing mixtures of silicone oil and squalene are dispersed in a
      simple aqueous surfactant solution, quenched in liquid ethane, and examined using
      cryogenic transmission electron microscopy (CTEM). Depending on the phase of ice
      that forms around the nanodroplets and on the composition of the oil mixture,
      nanoinclusions can be observed inside oil nanodroplets, independent of surfactant
      type. Our observations suggest that these nanoinclusions arise from nucleation of
      vapor cavities as the water freezes and expands while the oil remains liquid
      during the quench.

PMID- 22881457
TI  - Intracranial EEG-fMRI analysis of focal epileptiform discharges in humans.
AB  - PURPOSE: Combining intracranial electroencephalography (iEEG) with functional
      magnetic resonance imaging (fMRI) is of interest in epilepsy studies as it would
      allow the detection of much smaller interictal epileptiform discharges than can
      be recorded using scalp EEG-fMRI. This may help elucidate the spatiotemporal
      mechanisms underlying the generation of interictal discharges. To our knowledge,
      iEEG-fMRI has never been performed at 3 Tesla (3T) in humans. We report our
      findings relating to spike-associated blood oxygen level-dependent (BOLD) signal
      changes in two subjects. METHODS: iEEG-fMRI at 3T was performed in two subjects.
      Twelve channels of iEEG were recorded from subdural strips implanted on the left
      posterior temporal and middle frontal lobes in a 20-year-old female with
      bilateral periventricular gray matter heterotopia. Twenty channels of iEEG were
      recorded bilaterally from two subdural strips laid anterior-posterior along
      mesial temporal surfaces in a 29-year-old woman with bilateral temporal seizures
      and mild left amygdalar enlargement on MRI. Functional MRI (fMRI) statistical
      maps were generated and thresholded at p = 0.01. KEY FINDINGS: No adverse events
      were noted. A total of 105 interictal discharges were recorded in the posterior
      middle temporal gyrus of Subject 1. In Subject 2, 478 discharges were recorded
      from both mesial temporal surfaces (n = 194 left, 284 right). The right and left
      discharges were modeled separately, as they were independent. Subject 1 showed
      spike-associated BOLD signal increases in the left superior temporal region, left
      middle frontal gyrus, and right parietal lobe. BOLD decreases were seen in the
      right frontal and parietal lobes. In Subject 2, BOLD signal increases were seen
      in both mesial temporal lobes, which when left and right spikes were modeled
      independently, were greater on the side of the discharge. In addition, striking
      BOLD signal decreases were observed in the thalamus and posterior cingulate
      gyrus. SIGNIFICANCE: iEEG-fMRI can be performed at 3T with low risk. Notably,
      runs of only 5 or 10 min of EEG-fMRI were performed as part of our implementation
      protocol, yet a significant number of epileptiform discharges were recorded,
      allowing meaningful analyses. With these studies, we have shown that deactivation
      can be seen in individual subjects with focal epileptiform discharges. These
      preliminary observations suggest a novel mechanism through which focal interictal
      discharges may have widespread cortical and subcortical influences.

PMID- 22881458
TI  - Crosstalk on cell behavior in interactive cocultures of hMSCs with various oral
      cell types.
AB  - When prospectively applied for regenerative therapies, human bone-marrow-derived
      mesenchymal stem cells (hMSCs) interact with the locally residing host cells.
      With respect to the developmentally particular origin of oral cells, little is
      known about the putatively discriminative behavioral responses of hMSCs in
      interaction with various oral cell types, including human alveolar bone
      osteoblasts (hOAs), periodontal ligament fibroblasts (hPDLs), and gingival
      fibroblasts (hGFs). To assess the crosstalk between hMSCs and oral cells,
      interactive cocultures were established by combining well-characterized hMSCs
      with hOAs, hPDLs, or hGFs, and the behavioral hMSC aspects, that is,
      proliferation and gene expression, were measured by employing a 5-bromo-2'
      deoxyuridine assay and real-time polymerase chain reaction, while apoptosis was
      quantified by in situ cell death detection kit. hMSCs expressed the typical
      antigen spectrum lacking CD34, CD45, CD14, CD19, and HLA-DR, while expressing
      CD73, CD90, and CD105, and could successfully be transformed into adipocytes,
      osteocytes, and chondrocytes. Monocultured control hMSCs proliferated readily,
      whereas a general reduction of BrdU-labeled cells was observed in cocultures.
      Globally, upon extending time periods, interactive coculture combinations of
      hMSCs with hOAs reduced both osteogenic gene and stem cell marker transcription
      in hMSCs, a phenomenon appearing less pronounced by combining hMSCs with hPDLs,
      such that the observed effects in terms of proliferation and gene expression
      followed the same ranking: hOAs>hGFs>hPDLs. Vice versa, in interactive hMSC
      cocultures, the cell survival rate was significantly increased, irrespective from
      the combined coculture cell counterpart. Our results show for the first time that
      behavior of hMSCs reflected by proliferation and gene expression was governed by
      interaction with various oral cells in a cell-type-discriminative manner. In
      addition, hMSC coculture restrains apoptosis, such that influences on cell
      behavior appear as a crosstalk. In summary, interactive cocultures render the
      basis for a prospective prediction of mutual cell behavior in hMSC-based oral
      tissue regeneration disclosing that oral cells shift hMSC behavior from
      proliferation to differentiation and apoptosis-repressing features.

PMID- 22881460
TI  - The apical polarity protein network in Drosophila epithelial cells: regulation of
      polarity, junctions, morphogenesis, cell growth, and survival.
AB  - Epithelial tissue formation and function requires the apical-basal polarization
      of individual epithelial cells. Apical polarity regulators (APRs) are an
      evolutionarily conserved group of key factors that govern polarity and several
      other aspects of epithelial differentiation. APRs compose a diverse set of
      molecules including a transmembrane protein (Crumbs), a serine/threonine kinase
      (aPKC), a lipid phosphatase (PTEN), a small GTPase (Cdc42), FERM domain proteins
      (Moesin, Yurt), and several adaptor or scaffolding proteins (Bazooka/Par3, Par6,
      Stardust, Patj). These proteins form a dynamic cooperative network that is
      engaged in negative-feedback regulation with basolateral polarity factors to set
      up the epithelial apical-basal axis. APRs support the formation of the apical
      junctional complex and the segregation of the junctional domain from the apical
      membrane. It is becoming increasingly clear that APRs interact with the
      cytoskeleton and vesicle trafficking machinery, regulate morphogenesis, and
      modulate epithelial cell growth and survival. Not surprisingly, APRs have
      multiple fundamental links to human diseases such as cancer and blindness.

PMID- 22881461
TI  - Unpacking the impoverished nature of secondary forests.
AB  - In a world where even documenting species declines in tropical systems is
      challenging enough, Klimes et al. raise the bar by addressing the deceptively
      simple, yet inherently complex, question of why species richness is lower in
      secondary forests. Using the first plot-scale inventory of arboreal ant nests,
      combined with an innovative rarefaction technique, they quantify the relative
      importance of a range of successional factors and highlight the contribution of
      beta diversity to the higher richness in primary forest.

PMID- 22881462
TI  - Dental health of homeless adults in Toronto, Canada.
AB  - OBJECTIVES: This study aimed to assess the oral health status of the Toronto
      adult homeless population; to learn how they perceive their own oral health; and
      to correlate the presence of oral disease with length of homelessness and
      unemployment. METHODS: This cross-sectional descriptive study collected data from
      191 homeless adults who were randomly selected using a stratified cluster sample
      at 18 shelters. A questionnaire and clinical oral examination were conducted with
      participants. RESULTS: The mean Decayed/Missing/Filled Teeth (DMFT) score of the
      subjects was 14.4 (SD = 8.1). Only 32% of them had visited a dentist during the
      last year, 75% believed that they had untreated dental conditions, and 40% had
      their last dental visit for emergency care. The clinical oral examination
      observed that 88% needed fillings, 70% periodontal, 60% prosthodontic, and 40%
      emergency treatment. CONCLUSION: Homeless adults in Toronto have poor oral
      health, significant oral health treatment needs, and a lack of access to dental
      care.

PMID- 22881459
TI  - Cell polarity as a regulator of cancer cell behavior plasticity.
AB  - Cell polarization is an evolutionarily conserved process that facilitates
      asymmetric distribution of organelles and proteins and that is modified
      dynamically during physiological processes such as cell division, migration, and
      morphogenesis. The plasticity with which cells change their behavior and
      phenotype in response to cell intrinsic and extrinsic cues is an essential
      feature of normal physiology. In disease states such as cancer, cells lose their
      ability to behave normally in response to physiological cues. A molecular
      understanding of mechanisms that alter the behavior of cancer cells is limited.
      Cell polarity proteins are a recognized class of molecules that can receive and
      interpret both intrinsic and extrinsic signals to modulate cell behavior. In this
      review, we discuss how cell polarity proteins regulate a diverse array of
      biological processes and how they can contribute to alterations in the behavior
      of cancer cells.

PMID- 22881463
TI  - Misidentification of maternal heart rate as fetal on cardiotocography during the
      second stage of labor: the role of the fetal electrocardiograph.
AB  - OBJECTIVE: To identify the incidence of fetal heart rate (FHR) accelerations in
      the second stage of labor and the role of fetal electrocardiograph (ECG) in
      avoiding misidentification of maternal heart rate (MHR) as FHR. DESIGN:
      Retrospective observational study. SETTING: University hospital labor ward,
      London, UK. SAMPLE: Cardiotocograph (CTG) tracings of 100 fetuses monitored using
      external transducers and internal scalp electrodes. METHODS: CTG traces that
      fulfilled inclusion criteria were selected from an electronic FHR monitoring
      database. MAIN OUTCOME MEASURES: Rate of accelerations during external and
      internal monitoring as well as decelerations for a period of 60 minutes prior to
      delivery were determined. The role of fetal ECG in differentiating between MHR
      and FHR trace was explored. RESULTS: Decelerations occurred in 89% of CTG traces
      during the second stage of labor. Accelerations indicating possible recording of
      FHR or MHR were found in 28.1 and 10.9% of cases recorded by an external
      ultrasound transducer as well as internal scalp electrode, respectively.
      Accelerations coinciding with uterine contractions occurred only in 11.7 and 4%
      of external and internal recording of FHR, respectively. Absence of 'p-wave' of
      the ECG waveform was associated with MHR trace. CONCLUSION: Decelerations were
      the commonest CTG feature during the second stage of labor. The incidence of
      accelerations coinciding with uterine contractions was less than half in fetuses
      monitored using a fetal scalp electrode. Analysing the ECG waveform for the
      absence of 'p-wave' helps in differentiating MHR from FHR.

PMID- 22881464
TI  - The management of toxic epidermal necrolysis.
AB  - The mortality rate of Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN) is high; approximately 5% for SJS and 25% for TEN. It is
      therefore vital for the treating physician to recognise SJS and TEN promptly
      through the identification of these diseases' characteristic clinical features so
      that the offending drug is promptly withdrawn, supportive therapy is administered
      and adjunctive therapies are considered. Supportive therapy addressing the
      manifestations and complications of acute skin failure include monitoring the
      fluid - electrolyte balance and providing enteral or parenteral nutrition, wound
      care and treatment of sepsis. In addition, supportive care of the affected
      mucosal surfaces is required through the use of aggressive ocular lubrication,
      topical corticosteroids, hygienic mouthwashes and oral anaesthetics, together
      with monitoring for urinary retention. There is sufficient evidence for the use
      of intravenous immune globulin in the acute management of SJS/TEN provided an
      adequate dose of 2-3 g/kg is administered. Cyclosporine appears to also be an
      effective agent although randomised control studies are required to demonstrate
      its benefit and establish the dose, duration of therapy and safety profile. The
      role of corticosteroids is currently under revision. Some earlier studies have
      shown a lack of efficacy or increased mortality in their use but the use of high
      doses early in the course of disease may actually reduce morbidity and mortality.
      The role of plasmapheresis, anti-tumour necrosis factor (TNF) biologics and N
      acetylcysteine is promising but further studies are required to elucidate their
      benefit. Preventative strategies such as pharmacogenetic screening needs to be
      strongly considered, with the provision of cost-effective assays with a rapid
      turn-around time.

PMID- 22881465
TI  - Split-leg comparison of low fluence diode laser and high fluence intense pulsed
      light in permanent hair reduction in skin types III to IV.
AB  - BACKGROUND/OBJECTIVES:   All the standard light-based techniques for permanent
      hair reduction, like laser and intense pulsed light (IPL) employ the highest
      tolerable fluence with a single pass. As opposed to standard techniques, a new
      diode laser technique employs low fluence with multiple passes. Here we evaluate
      and compare the efficacy, treatment time, comfort and safety of the low fluence
      multiple pass diode laser with high fluence single pass IPL for permanent hair
      reduction in Type III to IV Asian patients. METHODS:   Thirty Asian patients with
      Type III to IV black hair were enrolled and received three sessions of treatments
      at 6-weekly to 8-weekly intervals. A split-leg study was performed in which the
      IPL was applied to one leg of each patient while the laser was applied to the
      other. The patients were followed up for 12 months. RESULTS:   All patients were
      satisfied with the results of the long-term hair reduction without long-term side
      effects. There was no statistically significant difference in hair reduction and
      treatment time between the laser (76.85%, 21.39 min) and the IPL (74.53%, 22.17
      min) (P > 0.05). The visual analogue scale (VAS) pain score of the IPL (5.96) was
      higher than that of the laser (3.10) (P < 0.01). CONCLUSIONS:   A series of high
      fluence single pass IPL and low fluence multiple pass diode laser treatments were
      performed with similar efficacy, speed and safety for permanent hair reduction.
      However, low fluence multiple pass diode laser treatment was less painful than
      high fluence single pass IPL.

PMID- 22881466
TI  - Low-dose cyclosporin improves the health-related quality of life in Japanese
      psoriasis patients dissatisfied with topical corticosteroid monotherapy.
AB  - Psoriasis greatly impacts the health-related quality of life of patients,
      including any dermatological conditions that are listed in the dermatology life
      quality index (DLQI). We investigated the relationships between DLQI and the
      degree of patient satisfaction using questionnaires among psoriasis patients
      treated only with topical corticosteroids. Patients who were dissatisfied with
      topical corticosteroids alone and agreed to receive cyclosporin were given low
      dose oral cyclosporin. We assessed changes of the DLQI and the psoriasis area and
      severity index (PASI) scores in patients dissatisfied with treatment during the
      period of cyclosporin addition. Of 32 enrolled patients, 17 reported
      dissatisfaction with the current treatment of topical corticosteroids alone.
      There was a significantly positive correlation between the degree of patient
      satisfaction questionnaires and the DLQI of these 32 patients. Among the 17
      dissatisfied patients, 12 patients agreed to receive additional cyclosporin
      therapy and five did not. The 12 patients who started on cyclosporin had a
      significantly lower PASI after 12 weeks than they did at baseline. The DLQI
      improved significantly after 12 weeks in the cyclosporin-treated patients. The 12
      patients who agreed to receive cyclosporin showed a significantly lower DLQI at
      12 weeks compared to the five patients who declined the addition of cyclosporin
      to their treatment. Assessing the degree of patient satisfaction with therapy
      using a questionnaire could be useful for improving clinical interventions in
      psoriasis patients. Low-dose oral cyclosporin could be effective in patients who
      are dissatisfied with topical corticosteroid treatment alone.

PMID- 22881467
TI  - Allergic contact dermatitis to topical preparations of bufexamac.
AB  - In Australia bufexamac is mainly used for pharmacist-initiated local treatment of
      various dermatoses. The European Medicines Agency's Committee for Medicinal
      Products for Human Use recently recommended that marketing authorisation for
      bufexamac-containing preparations be revoked throughout the European Union
      because of the risk of severe allergic contact dermatitis. We retrospectively
      reviewed the patch test database at the Skin and Cancer Foundation Inc. and
      identified 19 cases of positive reactions to bufexamac (5% petrolatum) from 451
      people patch tested. The bufexamac reaction was deemed relevant to the presenting
      dermatitis in 13 of 19 (68%) patients. Bufexamac allergic contact dermatitis is
      under-reported in the English literature. We wish to emphasise the severity and
      the unusually polymorphic eruptions observed in some of the cases. Clinicians
      should consider the possibility of allergic contact dermatitis to bufexamac
      containing preparations in all patients where there is a history of exposure,
      even if used for only a short time.

PMID- 22881468
TI  - Re.: Accuracy in skin cancer diagnosis: a retrospective study of an Australian
      public hospital dermatology department.

PMID- 22881469
TI  - Number needed to treat.

PMID- 22881472
TI  - Angiolymphoid hyperplasia with eosinophilia and Kimura's disease coexisting in
      the same patient: evidence for a spectrum of disease.
AB  - The relationship between angiolymphoid hyperplasia with eosinophilia (ALHE) and
      Kimura's disease has always been contentious. Initially, ALHE and Kimura's
      disease were thought to be conditions within the same disease spectrum, but it is
      now widely accepted that they are two separate disease entities. The two lesions
      may coexist in one patient. Thus, ALHE and Kimura's disease may be different
      manifestations of the one disease.

PMID- 22881473
TI  - Cutaneous angiosarcoma of the leg showing radiation sensitivity.
AB  - We report a case of cutaneous angiosarcoma occurring on the leg of a 97-year-old
      Japanese woman. Considering the patient's age and general condition, she was
      treated with electron beam irradiation, which led to the almost complete
      disappearance of the tumour. Because cutaneous angiosarcoma is an aggressive
      tumour with a high propensity for local recurrence and distant metastases,
      therapy preferably involves a multimodal approach. However, monotherapy with
      radiation may be effective in some cases of cutaneous angiosarcoma.

PMID- 22881474
TI  - Ulcerative necrobiosis lipoidica responsive to colchicine.
AB  - Necrobiosis lipoidica is an uncommon granulomatous disease of unknown aetiology.
      Few treatments have emerged with consistent efficacy and the ulcerated form of
      necrobiosis lipoidica can be particularly difficult to treat. A 56-year-old non
      diabetic woman with chronic ulcerative necrobiosis lipoidica unresponsive to
      other therapies was commenced on colchicine treatment. Complete resolution of the
      ulcers was observed after 2 months' therapy with colchicine 500 ug twice daily.

PMID- 22881475
TI  - Hydroxyurea induced dermatomyositis-like eruption.
AB  - Medication-induced dermatomyositis (DM) is rare, but a recent review highlighted
      hydroxyurea (HU) as the most common inciting agent. To aid diagnosis, HU-induced
      DM-like eruption (HU DM-LE) forms a distinct dermopathy where the typical
      cutaneous features of DM are without systemic involvement and co-exist with other
      HU-induced cutaneous findings such as severe xerosis, atrophy, stomatitis,
      cutaneous and mucosal ulceration and melanonychia. On cessation of HU the DM-LE
      clears avoiding unnecessary immunosuppression and demonstrating the importance of
      consideration of medication aetiology in DM presentations. We present a case
      report and review of the literature.

PMID- 22881476
TI  - Concurrence of alopecia areata and vitiligo at the same anatomical site.
AB  - Both alopecia areata and vitiligo are common skin disorders that are considered
      to be caused by an autoimmune response targeted to hair follicle and melanocyte
      antigens, respectively. The association of these two diseases in the same patient
      is well known, however, coexistence of alopecia areata and vitiligo within the
      same lesion is very rare. Herein, we report an 8-year-old boy who had
      colocalization of alopecia areata and vitiligo on the frontal portion of his
      scalp.

PMID- 22881477
TI  - Palmar herald patch in pityriasis rosea.
AB  - Pityriasis rosea is an acute self-limited inflammatory disorder of the skin. The
      initial clinical features of typical cases are the appearance of a herald patch.
      The herald patch is commonly located on the thigh, upper arm, trunk or neck;
      rarely the patch may be on the face, scalp or penis. There are no reports of a
      palmar herald patch in pityriasis rosea. In this article we present a 14-year-old
      male patient who had a palmar herald patch with truncal lesions of pityriasis
      rosea.

PMID- 22881478
TI  - Effect of different polymers and their combinations on the release of
      metoclopramide HCl from sustained-release hydrophilic matrix tablets.
AB  - Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal
      disorders. It has a short biological half-life and is usually administered four
      times daily to maintain effective concentrations throughout the day. The aim of
      this study is to develop sustained-release hydrophilic matrix tablet formulations
      of drug to achieve reproducible and predictable release rates, extended duration
      of activity, decreased toxicity, reduction of required dose, optimized therapy,
      and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC),
      carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were
      incorporated in the matrix system separately or in combinations as release
      controlling factor by direct compression technique. Compatibility among the
      formulation components was assessed by DSC and FTIR analysis. MTC release from
      matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All
      formulations met the criteria of pharmacopeial requirements. Dissolution studies
      show that polymer type and concentration are important parameters on drug
      release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug
      release profile whereas HPMC did not. All the formulations containing 1:1 ratio
      of HPMC and chitosan exhibited desired drug release showing that all active
      substance releases progressively in a period of whole dissolution time and
      therefore it can be regarded as worthy of consideration for the manufacture of
      sustained-release MTC product. 

PMID- 22881479
TI  - PolyMPC-doxorubicin prodrugs.
AB  - We demonstrate the conjugation of the cancer drug doxorubicin (DOX) to
      poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), linked by hydrazone
      groups, using (1) a one-pot ATRP/click sequence, and (2) a post-polymerization
      conjugation strategy. While the one-pot method gave polyMPC-DOX conjugates in a
      facile single step, post-polymerization conjugation gave higher-molecular-weight
      polymers with very high DOX loadings. DOX release from the polyMPC backbone was
      pH-dependent (faster at pH 5.0 than at pH 7.4) owing to the hydrazone linkage.
      Half-life values of DOX release ranged from 2 to 40 h at pH 5.0. Cell culture
      experiments showed that highly loaded polyMPC-DOX conjugates exhibited higher
      intracellular drug accumulation and lower half-maximal inhibitory concentration
      (IC(50)) values, while a polymer with 30 wt % drug loading showed a maximum
      tolerated dose in the range of 30-50 mg/kg DOX equivalent weight in healthy mice.

PMID- 22881480
TI  - Observations on 'Allergic fungal sinusitis: innocence under suspicion'.

PMID- 22881481
TI  - Mentorship in the context of interdisciplinary geriatric research: lessons
      learned from the RAND/Hartford Program for Building Interdisciplinary Geriatric
      Research Centers.
AB  - In light of the growing trend toward formalized research mentorship for
      effectively transmitting the values, standards, and practices of science from one
      generation of researchers to the next, this article provides the results of an
      exploratory study. It reports on research mentorship in the context of
      interdisciplinary geriatric research based on experiences with the RAND/Hartford
      Program for Building Interdisciplinary Geriatric Research Centers. At the end of
      the 2-year funding period, staff from the RAND Coordinating Center conducted 60-
      to 90-minute open-ended telephone interviews with the co-directors of the seven
      centers. Questions focused on interdisciplinary mentorship activities, barriers
      to implementing these activities, and strategies for overcoming them, as well as
      a self-assessment tool with regard to programs, policies, and structures across
      five domains, developed to encourage research mentorship. In addition, the
      mentees at the centers were surveyed to assess their experiences with
      interdisciplinary mentoring and the center. According to the interviewees, some
      barriers to successful interdisciplinary mentoring included the mentor's lack of
      time, structural support, and the lack of a clear definition of interdisciplinary
      research. Most centers had formal policies in place for mentor identification and
      limited policies on mentor incentives. Mentees uniformly reported their
      relationships with their mentors as positive. More than 50% of mentees reported
      having a primary mentor from within their discipline and had more contact with
      their primary mentor than their secondary mentors. Further research is needed to
      understand the complexity of institutional levers that emerging programs might
      employ to encourage and support research mentorship.

PMID- 22881482
TI  - Transposition surgery for internuclear ophthalmoplegia.
AB  - PURPOSE: To report outcomes of an extraocular muscle transposition procedure for
      surgical correction of internuclear ophthalmoplegia. METHODS: Records of patients
      operated on between January 1999 and May 2011 were reviewed to identify patients
      treated with an extraocular muscle transposition procedure for internuclear
      ophthalmoplegia. Indications for this procedure included a known unilateral or
      bilateral internuclear ophthalmoplegia with a large-angle exotropia, a moderate
      adduction limitation, and a large-angle exodeviation in primary position. All
      patients underwent orthoptic evaluation preoperatively and postoperatively.
      Examination included assessment of subjective complaints, visual acuity,
      deviation in diagnostic positions of gaze, and limitation of ocular motility.
      RESULTS: Five patients were identified. The mean reduction in exodeviation at
      distance after surgery was 59 +/- 25 prism diopters, giving a mean percent
      reduction in exodeviation of 99.6% +/- 0.1%. Four of five patients achieved
      primary position orthotropia at distance; the remaining patient had 2 prism
      diopters of exodeviation. One patient who had a residual exodeviation after the
      initial transposition procedure did not have accompanying ipsilateral lateral
      rectus recession, but achieved orthotropia with a subsequent ipsilateral lateral
      rectus recession. CONCLUSION: Transposition surgery is an effective option for
      surgical treatment of patients with internuclear ophthalmoplegia with
      exodeviation and diplopia when combined with ipsilateral lateral rectus
      recession.

PMID- 22881483
TI  - Tear osmolarity in premature infants.
AB  - PURPOSE: To measure and report tear osmolarity in premature infants and to assess
      the change, if any, that occurs with increasing maturity. METHODS: In a
      prospective study of consecutive infants born at less than 37 weeks gestational
      age undergoing screening for retinopathy of prematurity, serial measurements of
      tear osmolarity were obtained at preterm, term, and 3 months post-term. Mean +/-
      standard deviation tear osmolarity and percentage of infants with tear osmolarity
      value greater than 308 and greater than 316 mOsm/L were calculated at each stage
      of maturity. RESULTS: Twenty-five premature infants of mean post-conceptional age
      33.5 weeks and mean birth weight 1,159 +/- 259 g were tested. Mean tear
      osmolarity was 296 +/- 19.1, 302.8 +/- 18, and 301.1 +/- 20.9 mOsm/L at pre-term,
      term, and post-term, respectively. There was no significant effect for time on
      tear osmolarity values (P = .59). Tear osmolarity was greater than 308 mOsm/L in
      32% and greater than 316 mOsm/L in 16%. CONCLUSION: Mean tear osmolarity in
      premature infants is within the expected normal range for adults and shows no
      significant change at term or post-term. More than two-thirds of premature
      infants have tear osmolarity values below the suggested diagnostic cut-offs for
      dry eye disease in adults. Most preterm infants do not have a dry eye based on
      assessment of tear osmolarity.

PMID- 22881484
TI  - Development of a signal-ratio-based antioxidant index for assisting the
      identification of polyphenolic compounds by mass spectrometry.
AB  - A new concept, called the signal-ratio-based antioxidant index (SRBAI), is
      proposed for the identification of antioxidants. The SRBAI is derived from the
      signal ratio of free-radical scavenging to polyphenolic chromophore absorbance.
      Each SRBAI value corresponds to a specific antioxidant under the same antioxidant
      assay condition. Hence, the SRBAI can be used as an identification card of the
      antioxidant, which can resolve even components with the same retention time or
      with similar mass fragmentation spectra. We employed onion and several quercetin
      glycosides as models. There are four major peaks of onion with free-radical
      scavenging ability. One of the peaks failed to be identified; for the authentic
      compounds, quercetion-3-glucoside (SRBAI = 8.98) and quercetin-3-rutinoside
      (SRBAI = 3.01) eluted at the same retention time as the unknown peak. However,
      the unknown was considered to be quercetin-3-glucoside for its SRBAI was 8.91.
      SRBAI values also can be applied to differentiate the unknown peaks with the same
      parent ion of m/z 463 and collision-induced dissociation (CID) spectra as the two
      authentic compounds, quercetin-3-glucoside and quercetin-4'-glucoside. This newly
      introduced SRBAI can act as an efficient and precise identification tool,
      especially for online identification of similar polyphenolic isomers.

PMID- 22881485
TI  - Removal of trace organic micropollutants by drinking water biological filters.
AB  - The long-term removal of 34 trace organic micropollutants (<1 MUg L(-1)) was
      evaluated and modeled in drinking water biological filters with sand media from a
      full-scale plant. The micropollutants included pesticides, pharmaceuticals, and
      personal care products, some of which are endocrine disrupting chemicals, and
      represent a wide range of uses, chemical structures, adsorbabilities, and
      biodegradabilities. Micropollutant removal ranged from no measurable removal
      (<15%) for 13 compounds to removal below the detection limit and followed one of
      four trends over the one year study period: steady state removal throughout,
      increasing removal to steady state (acclimation), decreasing removal, or no
      removal (recalcitrant). Removals for all 19 nonrecalcitrant compounds followed
      first-order kinetics when at steady state with increased removal at longer empty
      bed contact times (EBCT). Rate constants were calculated, 0.02-0.37 min(-1), and
      used in a pseudo-first-order rate model with the EBCT to predict removals in
      laboratory biofilters at a different EBCT and influent conditions. Drinking water
      biofiltration has the potential to be an effective process for the control of
      many trace organic contaminants and a pseudo-first-order model can serve as an
      appropriate method for approximating performance.

PMID- 22881486
TI  - Combined staged therapy of complex arteriovenous malformations: initial
      experience.
AB  - OBJECTIVES: Definitive treatment of complex supratentorial arteriovenous
      malformations (AVMs) has been classically assigned to ruptured or progressively
      symptomatic cases. The aim of this study is to report our initial experience in
      the treatment of complex AVMs by means of staged embolization with Onyx followed
      by microsurgery. MATERIAL AND METHODS: Thirteen consecutive patients with
      supratentorial Spetzler-Martin grades III, IV and V AVMs were treated between
      January 2009 and June 2010. Mean age at the beginning of the therapy was 34. All
      patients were symptomatic. Mean AVM size was 48 mm, and mean volume prior to
      embolization was 47 ml. RESULTS: Mean number of endovascular procedures was 3,
      and mean volumetric obliteration prior to surgery was 79.2%. Mean time between
      two embolizations was 24 days. One patient showed a non-disabling complication
      after endovascular procedures. Mean time between the last embolization and
      surgery was 42 days. Two patients showed disabling complications after surgery,
      and one patient showed a non-disabling complication. Follow-up angiography showed
      the complete removal of permeable AVM in all patients. According to the modified
      Rankin Scale, all patients were non-dependent concerning daily life activity at 6
      month follow-up. One-year follow-up angiography has been performed in 11 patients
      so far showing an absence of permeable AVM in spite of the remainder
      intravascular Onyx. CONCLUSIONS: Staged preoperative embolization with Onyx
      followed by microsurgery has made possible 100% cure of complex AVMs with 0%
      mortality, 15.4% disabling complications and 15.4% non-disabling complications.
      Complete Onyx resection is not essential to achieve the cure of the patient.

PMID- 22881577
TI  - Understanding rubredoxin redox sites by density functional theory studies of
      analogues.
AB  - Determining the redox energetics of redox site analogues of metalloproteins is
      essential in unraveling the various contributions to electron transfer properties
      of these proteins. Since studies of the [4Fe-4S] analogues show that the energies
      are dependent on the ligand dihedral angles, broken symmetry density functional
      theory (BS-DFT) with the B3LYP functional and double-zeta basis sets calculations
      of optimized geometries and electron detachment energies of [1Fe] rubredoxin
      analogues are compared to crystal structures and gas-phase photoelectron
      spectroscopy data, respectively, for [Fe(SCH(3))(4)](0/1-/2-), [Fe(S(2)-o
      xyl)(2)](0/1-/2-), and Na(+)[Fe(S(2)-o-xyl)(2)](1-/2-) in different
      conformations. In particular, the study of Na(+)[Fe(S(2)-o-xyl)(2)](1-/2-) is the
      only direct comparison of calculated and experimental gas phase detachment
      energies for the 1-/2- couple found in the rubredoxins. These results show that
      variations in the inner sphere energetics by up to ~0.4 eV can be caused by
      differences in the ligand dihedral angles in either or both redox states.
      Moreover, these results indicate that the protein stabilizes the conformation
      that favors reduction. In addition, the free energies and reorganization energies
      of oxidation and reduction as well as electrostatic potential charges are
      calculated, which can be used as estimates in continuum electrostatic
      calculations of electron transfer properties of [1Fe] proteins.

PMID- 22881578
TI  - Nitric oxide dioxygenation reaction by oxy-coboglobin models: in-situ low
      temperature FTIR characterization of coordinated peroxynitrite.
AB  - The oxy-cobolglobin models of the general formula (NH(3))Co(Por)(O(2)) (Por =
      meso-tetra-phenyl and meso-tetra-p-tolylporphyrinato dianions) were constructed
      by sequential low temperature interaction of NH(3) and dioxygen with microporous
      layers of Co-porphyrins. At cryogenic temperatures small increments of NO were
      introduced into the cryostat and the following reactions were monitored by the
      FTIR and UV-visible spectroscopy during slow warming. Upon warming the layers
      from 80 to 120 K a set of new IR bands grows with correlating intensities along
      with the consumption of the nu(O(2)) band. Isotope labeling experiments with
      (18)O(2), (15)NO and N(18)O along with DFT calculations provides a basis for
      assigning them to the six-coordinate peroxynitrite complexes
      (NH(3))Co(Por)(OONO). Over the course of warming the layers from 140 to 170 K
      these complexes decompose and there are spectral features suggesting the
      formation of nitrogen dioxide NO(2). Upon keeping the layers at 180-210 K the
      bands of NO(2) gradually decrease in intensity and the set of new bands grows in
      the range of 1480, 1270, and 980 cm(-1). These bands have their isotopic
      counterparts when (15)NO, (18)O(2) and N(18)O are used in the experiments and
      certainly belong to the 6-coordinate nitrato complexes (NH(3))Co(Por)(eta(1)
      ONO(2)) demonstrating the ability of oxy coboglobin models to promote the nitric
      oxide dioxygenation (NOD) reaction similar to oxy-hemes. As in the case of Hb, Mb
      and model iron-porphyrins, the six-coordinate nitrato complexes are not stable at
      room temperature and dissociate to give nitrate anion and oxidized cationic
      complex Co(III)(Por)(NH(3))(1,2).

PMID- 22881579
TI  - Teledermatology operational considerations, challenges, and benefits: the
      referring providers' perspective.
AB  - BACKGROUND: Teledermatology has been used to provide increased specialty access
      for medically underserved communities. In California, policies enable the
      California Medicaid (Medi-Cal) program to provide reimbursement for both store
      and-forward (S&F) and live-interactive teledermatology consultations. To assess
      the effectiveness of teledermatology operations for this population,
      understanding the referring providers' perspective is crucial. The primary
      objective of this study was to explore the perspective of referring primary care
      providers (PCPs) on teledermatology by focusing on the operational
      considerations, challenges, and benefits to participating in teledermatology
      referral in the context of the Medi-Cal population. SUBJECTS AND METHODS: We
      conducted hour-long one-on-one interviews with 10 PCPs who refer patients to
      teledermatology regularly and who together serve an average aggregate referral
      base of 2,760 teledermatology cases yearly. RESULTS: Of the 2,760 aggregate
      annual teledermatology referrals, PCPs reported that they serve predominantly
      uninsured or underinsured populations and participate in S&F consultations. The
      majority of surveyed PCPs treat common skin conditions themselves. However, these
      PCPs refer more patients to teledermatology consultations than in-person
      dermatology encounters. Several factors influence PCPs' decision to refer to
      teledermatology, which include complexity of the skin problem, distance to
      accessible dermatologist, patient's insurance, and patient's preferences. PCPs
      identified improved workflow, enhanced communication with dermatologists, and
      faster turnaround for recommendations as three areas that referring physicians
      would like improved in their experience with teledermatology. CONCLUSIONS:
      Understanding the referring provider's perspective and subsequently adopting
      policy and practice solutions to address their challenges are vital to prompting
      further teledermatology participation for underserved communities.

PMID- 22881580
TI  - Associations between students' situational interest, mastery experiences, and
      physical activity levels in an interactive dance game.
AB  - The purpose of this study was to examine the influence of previous experiences on
      students' situational interest and physical activity (PA) levels, as well as the
      relationships between situational interest and PA levels in Dance Dance
      Revolution (DDR). A total of 135 seventh through ninth graders participated in
      DDR unit for two weeks, and reported their previous DDR experiences. Students' PA
      levels were measured by ActiGraph accelerometers for three classes with
      percentages of time spent in moderate to vigorous physical activity (MVPA) as the
      outcome variable. They also responded to the Situational Interest Scale
      (including novelty, challenge, attention demand, exploration intention, and
      instant enjoyment) at the end of each class. The multivariate analysis of
      covariance (MANCOVA) yielded a significant main effect for experience. Follow-up
      tests revealed that students with DDR experiences scored significantly higher
      than those without experiences at following dimensions: challenge; exploration
      intention; instant enjoyment; and attention demand. Regression analysis yielded
      that novelty emerged as the only significant predictor for MVPA. The findings
      suggested that four dimensions of situational interest differed between students
      with and without previous experiences. Novelty emerged as the only predictor for
      MVPA, suggesting that students would have higher PA when they feel the activity
      provides new information.

PMID- 22881581
TI  - Time is moving fast.

PMID- 22881582
TI  - Known and potential new risk factors for skin cancer in European populations: a
      multicentre case-control study.
AB  - BACKGROUND: During recent years numerous studies have suggested that personal and
      environmental factors might influence cancer development. OBJECTIVES: To
      investigate environmental and personal characteristics associated with skin
      cancer risk. METHODS: A multicentre hospital-based case-control study was
      performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain,
      including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell
      carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control
      persons. Exposures were assessed by questionnaires that were partly self
      administered, partly completed by dermatologists. Unconditional logistic
      regression modelling was used to assess associations including the influence of
      certain drugs and food items on skin cancer risk. RESULTS: The usual associations
      were observed for sun exposure and pigmentation characteristics, with chronic sun
      exposure being most strongly associated with SCC risk, and naevi and atypical
      naevi with CMM risk. Use of ciprofloxacin was associated with a decreased risk of
      BCC [odds ratio (OR) 0.33] and use of thiazide diuretics was associated with an
      increased risk of SCC (OR 1.66). Ciprofloxacin was also associated with SCC (OR
      0.34) and thiazines with BCC (OR 2.04), but these associations lost significance
      after correction for multiple testing. Consumption of pomegranate, rich in
      antioxidants, was associated with decreased BCC and SCC risk, also after
      correcting for multiple testing. Recent experience of stressful events was
      associated with increased risk, particularly of CMM. CONCLUSIONS: In this large
      case-control study from across Europe the expected associations were observed for
      known risk factors. Some new potential protective factors and potential risk
      factors were identified for consumption of certain food items, medication use and
      stress, which deserve further investigation in future studies.

PMID- 22881583
TI  - Health literacy, sunscreen and sunbed use: an uneasy association.
AB  - BACKGROUND: Skin cancer can largely be prevented by avoiding unsafe ultraviolet
      radiation (UVR) exposure. The evidence on potential drivers of sunscreen and
      sunbed use is extensive, yet in some cases, such as education, remains rather
      unclear. Health literacy is receiving increasing attention, but its effect on
      tanning decisions has not yet been explored. OBJECTIVES: To explore the
      association between health literacy and tanning behaviour, in terms of sunscreen
      and sunbed use. METHODS: Self-reported data were collected through a common
      questionnaire in eight European countries under a common protocol. A three-item
      measure was used to assess health literacy; one item was collected to measure
      current sunscreen use and one item to measure current sunbed use. Descriptive
      statistics and analysis of variance tests were applied to explore the profile of
      sunbed and sunscreen users and health literacy among a number of variables.
      Univariate and multivariate logistic regressions were used to assess the relation
      between health literacy and sunscreen and sunbed use. RESULTS: Univariate results
      suggested that health literacy has opposite effects on sunscreen use vs. sunbed
      use. Increased health literacy was associated with the skin cancer protective
      practice of using sunscreen, but also with more sunbed use. In the multivariate
      models, health literacy had a significant effect only on sunscreen use.
      CONCLUSIONS: The findings suggest that health literacy can be an interesting
      approach for influencing sunscreen use. In the case of sunbeds, based on the
      findings and contrary to what was expected, it can be argued that interventions
      targeting health literacy seem less likely to reduce sunbed use. More research is
      needed to elucidate the effect of health literacy on sunscreen and sunbed use in
      order to improve UVR prevention strategies.

PMID- 22881584
TI  - Basal cell carcinomas without histological confirmation and their treatment: an
      audit in four European regions.
AB  - BACKGROUND: Limited data are available on how often basal cell carcinomas (BCCs)
      are clinically diagnosed without histological confirmation and how they are
      treated. OBJECTIVES: Within the framework of the EPIDERM project, an audit was
      conducted in four European countries to study the occurrence of clinically
      diagnosed BCCs without histological confirmation and to investigate how these are
      treated. METHODS: In the Netherlands, Scotland, Finland and Malta studies were
      performed within different timeframes. Patients with one or more BCC(s) were
      selected and the number of clinically diagnosed BCCs without histological
      confirmation and their treatment was investigated by (manually) reviewing the
      (electronic) patient records and checking the (hospital) pathology databases to
      find evidence of histological confirmation. RESULTS: In the Netherlands, 1089
      patients with a first histologically confirmed BCC developed 1974 BCCs of which
      1833 (92.9%) were histologically confirmed and 141 (7.1%) were not. A 4-month
      retrospective study conducted in Scotland selected 294 patients with 344 BCCs;
      306 (89.0%) were histologically confirmed and 38 (11.0%) were not. A 3-month
      prospective study performed at the same centre in Scotland identified 44 patients
      who developed 58 BCCs; 44 (75.9%) of these were histologically confirmed and 14
      (24.1%) were not. In Finland, there were 701 patients who developed 977 BCCs, of
      which 807 (82.6%) were histologically and 170 (17.4%) nonhistologically
      confirmed. In Malta, there were 420 patients with 477 BCCs. Only three (0.7%) of
      them were clinically diagnosed without histological confirmation. In the
      Netherlands and Finland, clinically diagnosed BCCs without histological
      confirmation were most often treated with cryotherapy, whereas in Scotland 5%
      imiquimod cream was the preferred treatment modality. CONCLUSIONS: Although the
      frequency of clinically diagnosed BCCs without histological confirmation differed
      between the four European regions (range 0.7-24.1%), this confirms that the
      burden of BCC in Europe is underestimated when based on data from pathology
      and/or cancer registries.

PMID- 22881585
TI  - Assessing physicians' preferences on skin cancer treatment in Europe.
AB  - BACKGROUND: A wide variety of both surgical and nonsurgical therapies is
      currently available for patients with skin cancer. OBJECTIVES: This part of the
      EPIDERM (European Prevention Initiative for Dermatological Malignancies) project
      is aimed at the evaluation of the treatment preferences for skin cancer in eight
      countries of the European Union. METHODS: A multicentre hospital-based case
      control study was carried out at dermatology departments in Finland, Germany,
      Greece, Italy, Malta, Poland, Scotland and Spain. Patients with skin cancer
      (basal cell carcinoma, actinic keratosis, squamous cell carcinoma, cutaneous
      malignant melanoma and Bowen disease) were consecutively enrolled between July
      2008 and July 2010. Information on the study variables (sex, age, country, tumour
      type, anatomical location and treatment) was obtained from questionnaires
      designed by the EPIDERM project. RESULTS: In total, 1708 patients with skin
      cancer were included. Surgery was the first treatment option in 76.5% of the
      patients (P = 0.001). Actinic keratosis was the only tumour type in which
      nonsurgical treatment was more frequent than surgery (91.4%). Tumours on the head
      were less likely to be surgically excised than those at other locations (odds
      ratio 0.25, P = 0.001). Simple excision or curettage was the most common surgical
      procedure (65.4%), followed by graft and flaps (22.4%). Cryotherapy was the most
      common nonsurgical option (52.4%), followed by imiquimod (18.0%), photodynamic
      therapy (PDT; 12.0%), 5-fluorouracil (5-FU; 5.7%), and diclofenac with hyaluronic
      acid (4.0%). CONCLUSIONS: Surgery remains the first-choice treatment of skin
      cancer. Regarding nonsurgical treatments, the conservative treatments available
      (imiquimod, 5-FU, PDT and diclofenac gel) have not yet exceeded the use of
      ablative options such as cryotherapy despite their accepted benefit of treating
      field cancerization.

PMID- 22881586
TI  - Risk factors for actinic keratosis in eight European centres: a case-control
      study.
AB  - BACKGROUND: There are limited data regarding the association of actinic keratosis
      (AK) and other types of nonmelanoma skin cancer (NMSC); studies investigating
      possible correlation of AK with melanocytic naevi are even scarcer. To our
      knowledge, there are no data examining the risk of AK in people using specific
      medications. OBJECTIVE: To investigate constitutional and exposure risk factors
      leading to AK and the coexistence of AK with NMSC and melanoma. METHODS: A
      multicentre hospital-based case-control study was performed in Finland, Germany,
      Greece, Italy, Malta, Poland, Scotland and Spain, including 343 patients with
      actinic keratosis (AK), 409 with squamous cell carcinoma (SCC), 602 with basal
      cell carcinoma (BCC), 360 with invasive melanoma and 119 with in situ melanoma,
      and 686 control subjects. Exposures were assessed by questionnaires that were
      partly self-administered and partly filled out by dermatologists. Unconditional
      logistic regression modelling was used to assess associations including the
      influence of phenotypic characteristics, presence of naevi, sun-exposure habits
      and certain drugs on AK risk. RESULTS: Differences in hair and eye coloration
      variably influenced the risk for AK, with red hair signifying a seven times
      higher risk [odds ratio (OR) 6.9, 95% confidence interval (CI) 4.34-11.00), and
      brown - compared with blue - eyes, about a 40% reduced risk (OR 0.61, 95% CI 0.13
      0.92). The darker the skin phototype, the lower the risk for AK, with phototype
      IV exhibiting nine times less risk of developing AK. Some and many freckles on
      the arms were associated with an OR of 1.8 (95% CI 1.08-2.81) and 3.0 (95% CI
      1.10-3.54), respectively, while overall number of naevi and high educational
      level were inversely associated with AK. Sun exposure, thiazide diuretics and
      cardiac drugs had a higher risk for AK. SCC was the most frequent (58%) skin
      neoplasm coexisting with AKs, followed by BCC (30%), melanoma in situ (12%) and
      invasive melanoma (6%). CONCLUSION: In this large case-control study from across
      Europe the expected associations were confirmed for known risk factors. Some
      possible new risk factors, including cardiac and diuretic drugs, were identified,
      creating a new field for further investigation in future studies.

PMID- 22881587
TI  - The patient journey: a report of skin cancer care across Europe.
AB  - BACKGROUND: There are poorly documented variations in the journey a skin cancer
      patient will follow from diagnosis to treatment in the European Union.
      OBJECTIVES: To investigate the possible difficulties or obstacles that a person
      with a skin malignancy in the European Union may have to overcome in order to
      receive adequate medical screening and care for his/her condition. In addition,
      we wished to explore differences in European health systems, which may lead to
      health inequalities and health inequities within Europe. METHODS: Ten European
      countries took part in this investigation (in alphabetical order): Finland,
      Germany, Greece, Italy, Malta, Poland, Romania, Spain, the Netherlands and the
      U.K. The individual participants undertook local and national enquiries within
      their own country and completed a questionnaire. RESULTS: This exercise has
      identified important differences in the management of a skin cancer patient,
      reflecting major disparities in health care between European countries.
      CONCLUSIONS: Further investigation of health disparities and efforts to address
      health inequalities should lead to improvements in European health care quality
      and reduction in morbidity from skin cancer.

PMID- 22881588
TI  - Potential impact of interventions resulting in reduced exposure to ultraviolet
      (UV) radiation (UVA and UVB) on skin cancer incidence in four European countries,
      2010-2050.
AB  - BACKGROUND: Behavioural interventions to reduce exposure to ultraviolet radiation
      (UVR) can reduce risk of skin cancer. OBJECTIVES: To integrate the data and to
      evaluate the impact of interventions to limit exposure to UVR on skin cancer
      incidence in four selected countries. METHODS: Using PREVENT, a dynamic
      simulation model, we modelled the potential for skin cancer prevention in four
      European countries under various scenarios to avoid damage by UVR. RESULTS: In
      general, the most effective interventions were those aimed at protecting people
      during outdoor work and outdoor hobbies against the harmful effects of UVR, and
      combinations of several interventions. These could in theory lead to reductions
      of up to 45% in skin cancer cases projected for the year 2050. CONCLUSIONS: The
      scope for prevention depends on the prevalence of the risk factors in the
      different countries, as well as the associated risk factors and time lags
      modelled.

PMID- 22881589
TI  - Getting in early: primary skin cancer prevention at 55 German kindergartens.
AB  - BACKGROUND: Skin neoplasms are the most frequent types of neoplasms in white
      populations, and their incidence is increasing. Epidemiological studies have
      shown that the major environmental aetiological factor for their development is
      sunlight exposure. Sun protection programmes are urgently needed to raise
      awareness of the health hazards of ultraviolet radiation. In 2010 the 'SunPass'
      project was implemented at 55 kindergartens in Germany. This is the first
      nationwide environmental education programme for sun safety designed to teach
      children in kindergartens and their caregivers how to protect themselves from
      overexposure to the sun. OBJECTIVES: An interventional lecture, site inspections
      and a certification were part of the programme. Effects of these interventions
      were studied. METHODS: The gain in knowledge and changed sun-behavioural
      attributes were quantified by questionnaires administered before and after the
      'SunPass' interventions. RESULTS: The total number of children was 5424. Sun
      protection behaviour after the intervention improved significantly (P < 0.001).
      Among parents, 22.2% reported one to five sunburns of their child since birth.
      There was a significant increase in hat use by children in kindergartens (P =
      0.029), as well as some significantly improved shade practices. There was a
      significantly increased demand for protective clothing for children (P < 0.001).
      The change in sunscreen use in kindergartens was not significant. CONCLUSIONS:
      Although some aims of the 'SunPass' project were not fulfilled, such as the
      precise knowledge of skin types and a change of sunscreen use, the study had some
      positive outcomes in increasing the awareness of skin cancer and its prevention
      possibilities. The findings of the present study suggest that relatively brief
      interventions in kindergartens lead to improved sun protection of children. The
      whole investigation reaching over 5400 children and their parents underlines the
      importance of learning appropriate sun-protective behaviour in early childhood in
      order to decrease the risk for skin cancer.

PMID- 22881590
TI  - Running behind a tourist: leisure-related skin cancer prophylaxis.
AB  - The most important risk factor in the development of skin cancer is exposure to
      ultraviolet (UV) radiation. Cumulative lifetime UV radiation exposure has been
      shown to be most important in the pathogenesis of squamous cell carcinoma,
      whereas intermittent high-dose UV radiation exposure in childhood and adolescence
      may be more important in the aetiology of basal cell carcinoma and cutaneous
      malignant melanoma. Using established methodology and best available estimates on
      UV-related mortality and morbidity, it has been estimated that annually around
      1.5 million disability-adjusted life years are lost through excessive exposure to
      UV radiation. Skin cancer is a significant health problem and its burden is such
      that it causes the health system more to treat than any other forms of cancer.
      Prevention is the key action in managing skin cancer at a population level.
      Investment in prevention programmes such as SunSmart encourages protective
      behaviours that will reduce the human and financial costs of skin cancer.

PMID- 22881591
TI  - Occupational skin cancer induced by ultraviolet radiation and its prevention.
AB  - Skin cancer is by far the most common kind of cancer diagnosed in many western
      countries and ultraviolet radiation is the most important risk factor for
      cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although
      employees at several workplaces are exposed to increased levels of UV radiation,
      skin cancer due to long-term intense occupational exposure to UV radiation is
      often not considered as occupational disease. The actually available evidence in
      the epidemiological literature clearly indicates that occupational UV radiation
      exposure is a substantial and robust risk factor for the development of cutaneous
      SCC and also clearly shows a significant risk for developing BCC. There is enough
      scientific evidence that outdoor workers have an increased risk of developing
      work-related occupational skin cancer due to natural UV radiation exposure and
      adequate prevention strategies must be implemented. The three measures which are
      successful and of particular importance in the prevention of nonmelanoma skin
      cancer in outdoor workers are changes in behaviour regarding awareness of health
      and disease resulting from exposure to natural UV radiation, protection from
      direct UV radiation by wearing suitable clothing, and regular and correct use of
      appropriate sunscreens.

PMID- 22881592
TI  - Photoprotection in immunocompetent and immunocompromised people.
AB  - Ultraviolet radiation (UVR) exposure from the sun and artificial UV sources has
      been widely acknowledged as the major culprit for skin cancer and premature skin
      ageing. Skin cancers are among the most dangerous (cutaneous malignant melanoma)
      and the most numerous (basal cell carcinoma, actinic keratosis and invasive
      squamous cell carcinoma) of all neoplasms in the caucasian population worldwide.
      Skin cancers therefore have a significant impact on public health and healthcare
      costs, and will continue to do so. It is obvious that adequate photoprotection -
      seeking shade, wearing protective clothing and using sunscreens - is the key to
      reducing the harmful effects of UVR in both immunocompetent and immunocompromised
      people. This article provides background information on UVR, photoprotection
      (including the concept of topical sunscreen formulations), associated concerns
      regarding efficacy and safety, and behavioural and educational aspects of
      photoprotection and skin cancer prevention in immunocompetent and
      immunocompromised people. Certain persistent misconceptions and mistakes
      regarding photoprotection are also addressed.

PMID- 22881593
TI  - Effectiveness of skin cancer screening programmes.
AB  - Skin cancer, nonmelanoma skin cancer (NMSC) and cutaneous malignant melanoma
      (CMM), is the most frequent cancer worldwide. It is amenable to early detection,
      and screening for skin cancer has the potential to reduce mortality and
      morbidity. However, there are no recommendations for population-based skin cancer
      screening programmes due to the lack of evidence for the effectiveness from
      epidemiological studies. In 2008 the first nationwide screening programme for
      NMSC and CMM in the world was established in Germany. The decision for
      implementing such a programme was based on the results and evidence of a pilot
      study that was conducted from 2003 to 2004. The pilot study revealed that a
      population-based screening programme for skin cancer is feasible and effective.
      Careful evaluation of the nationwide programme is crucial to generate strong
      evidence for long-term public health benefits.

PMID- 22881594
TI  - Euromelanoma: a dermatology-led European campaign against nonmelanoma skin cancer
      and cutaneous melanoma. Past, present and future.
AB  - Euromelanoma is a dermatologist-led skin cancer prevention programme conducting
      an annual screening and public education campaign in over 20 European countries.
      Within its 10-year history, Euromelanoma has screened over 260,000 individuals
      across Europe, detecting a significant number of cutaneous melanomas and
      nonmelanoma skin cancers, identifying high-risk individuals for further
      surveillance and promoting awareness on the suspicious features of melanoma and
      the hazardous effects of ultraviolet exposure. In this review article, we
      summarize the history of the Euromelanoma campaign, present its organizational
      structure and discuss the results of the campaign in individual countries and on
      a European scale. Euromelanoma has had a significant impact on melanoma
      prevention and early diagnosis in participating countries and, despite many
      challenges, has positively influenced public health attitudes towards regular
      mole examination and the implementation of preventive measures against skin
      cancer.

PMID- 22881595
TI  - Psychological support of skin cancer patients.
AB  - The diagnosis of skin cancer imposes a great stress on our patients. Ultraviolet
      (UV) radiation-induced skin cancers are on the rise and frequently occur in
      younger patients and unexposed sites despite improved protective behaviour.
      Environmental factors and lifestyle habits have changed greatly in the last
      century and in addition to UV radiation exposure, psychosocial stressors and
      physical inactivity may play a role in the rising tumour incidence. With
      environmental stressors such as UV radiation they share the capacity to change
      the stress reaction. So far research into the interaction between stress, cancer
      and psychosocial intervention has generated some interesting results with respect
      to improvement of quality of life and the function of the hypothalamic-pituitary
      adrenal axis, the sympathetic axis and natural killer cells. These results hint
      at a suppressive effect of chronic stress on cellular immunity and the importance
      of a sufficient length and intensity of any psychosocial intervention for it to
      be effective. Nevertheless, the evidence remains inconclusive and does not take
      into account the findings of current psychoneuroimmunological research. This
      research has demonstrated the importance of a third stress axis along which
      neurotrophins and neuropeptides are effective. Along this axis, regulatory
      mechanisms may contribute to suppress tumoricidal immune responses. This may be
      instrumental in the establishment of an immune response that promotes tumour
      progression and holds important implications for integrated therapeutic
      strategies. However, research into the psychoneuroimmunological benefits of
      psychosocial intervention is largely missing, and future interdisciplinary
      research is warranted for understanding and further promoting improved quality of
      life and psychological as well as physical well-being after psychosocial
      intervention.

PMID- 22881596
TI  - Prevention initiative for dermatological malignancies: where do we stand?

PMID- 22881597
TI  - Loosening quantum confinement: observation of real conductivity caused by hole
      polarons in semiconductor nanocrystals smaller than the Bohr radius.
AB  - We report on the gradual evolution of the conductivity of spherical CdTe
      nanocrystals of increasing size from the regime of strong quantum confinement
      with truly discrete energy levels to the regime of weak confinement with closely
      spaced hole states. We use the high-frequency (terahertz) real and imaginary
      conductivities of optically injected carriers in the nanocrystals to report on
      the degree of quantum confinement. For the smaller CdTe nanocrystals (3 nm <
      radius < 5 nm), the complex terahertz conductivity is purely imaginary. For
      nanocrystals with radii exceeding 5 nm, we observe the onset of real
      conductivity, which is attributed to the increasingly smaller separation between
      the hole states. Remarkably, this onset occurs for a nanocrystal radius
      significantly smaller than the bulk exciton Bohr radius a(B) ~ 7 nm and cannot be
      explained by purely electronic transitions between hole states, as evidenced by
      tight-binding calculations. The real-valued conductivity observed in the larger
      nanocrystals can be explained by the emergence of mixed carrier-phonon, that is,
      polaron, states due to hole transitions that become resonant with, and couple
      strongly to, optical phonon modes for larger QDs. These polaron states possess
      larger oscillator strengths and broader absorption, and thereby give rise to
      enhanced real conductivity within the nanocrystals despite the confinement.

PMID- 22881598
TI  - Activation of the bile acid receptor GPBAR1 protects against gastrointestinal
      injury caused by non-steroidal anti-inflammatory drugs and aspirin in mice.
AB  - BACKGROUND AND PURPOSE: Low doses of aspirin (acetylsalicylic acid; ASA) and non
      steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal
      bleeding. GPBAR1 is a bile acid receptor expressed in the gastrointestinal tract.
      Here, we have investigated whether GPBAR1 was required for mucosal protection in
      models of gastrointestinal injury caused by ASA and NSAIDs. EXPERIMENTAL APPROCH:
      GPBAR1(+/+) and GPBAR1(-/-) mice were given ASA (10-50 mg.kg(-1)) or naproxen.
      Gastric and intestinal mucosal damage was assessed by measuring lesion scores.
      KEY RESULTS: Expression of GPBAR1, mRNA and protein, was detected in mouse
      stomach. Mice lacking GPBAR1 were more sensitive to gastric and intestinal injury
      caused by ASA and NSAIDs and exhibited a markedly reduced expression of
      cystathionine-gamma-liase (CSE), cystathionine-beta-synthase (CBS) and
      endothelial NOS enzymes required for generation of H(2)S and NO, in the stomach.
      Treating GPBAR1(+/+) mice with two GPBAR1 agonists, ciprofloxacin and betulinic
      acid, rescued mice from gastric injury caused by ASA and NSAIDs. The protective
      effect of these agents was lost in GPBAR1(-/-) mice. Inhibition of CSE by DL
      propargylglycine completely reversed protection afforded by ciprofloxacin in wild
      type mice, whereas treating mice with an H(2)S donor restored the protective
      effects of ciprofloxacin in GPBAR1(-/-) mice. Deletion of GPBAR1 altered the
      morphology of the small intestine and increased sensitivity to injury caused by
      naproxen. CONCLUSION AND IMPLICATIONS: GPBAR1 is essential to maintain gastric
      and intestinal mucosal integrity. GPBAR1 agonists protect against
      gastrointestinal injury caused by ASA and NSAIDs by a COX-independent mechanism.

PMID- 22881599
TI  - Mental health status in pregnancy among native and non-native Swedish-speaking
      women: a Bidens study.
AB  - OBJECTIVES: To describe mental health status in native and non-native Swedish
      speaking pregnant women and explore risk factors of depression and posttraumatic
      stress (PTS) symptoms. DESIGN AND SETTING: A cross-sectional questionnaire study
      was conducted at midwife-based antenatal clinics in Southern Sweden. SAMPLE: A
      non-selected group of women in mid-pregnancy. METHODS: Participants completed a
      questionnaire covering background characteristics, social support, life events,
      mental health variables and the short Edinburgh Depression Scale. MAIN OUTCOME
      MEASURES: Depressive symptoms during the past week and PTS symptoms during the
      past year. RESULTS: Out of 1003 women, 21.4% reported another language than
      Swedish as their mother tongue and were defined as non-native. These women were
      more likely to be younger, have fewer years of education, potential financial
      problems, and lack of social support. More non-native speakers self-reported
      depressive, PTS, anxiety and, psychosomatic symptoms, and fewer had had
      consultations with a psychiatrist or psychologist. Of all women, 13.8% had
      depressive symptoms defined by Edinburgh Depression Scale 7 or above. Non-native
      status was associated with statistically increased risks of depressive symptoms
      and having >=1 PTS symptom compared with native-speaking women. Multivariate
      modeling including all selected factors resulted in adjusted odds ratios for
      depressive symptoms of 1.75 (95% confidence interval: 1.11-2.76) and of 1.56 (95%
      confidence interval: 1.10-2.34) for PTS symptoms in non-native Swedish speakers.
      CONCLUSION: Non-native Swedish-speaking women had a more unfavorable mental
      health status than native speakers. In spite of this, non-native speaking women
      had sought less mental health care.

PMID- 22881600
TI  - Evaluation of co-processed excipients used for direct compression of orally
      disintegrating tablets (ODT) using novel disintegration apparatus.
AB  - The compendial method of evaluation of orodispersible tablets (ODT) is the same
      disintegration test as for conventional tablets. Since it does not reflect the
      disintegration process in the oral cavity, alternative methods are proposed that
      are more related to in vivo conditions, e.g. modified dissolution paddle
      apparatus, texture analyzer, rotating shaft apparatus, CCD camera application, or
      wetting time and water absorption ratio measurement. In this study, three
      different co-processed excipients for direct compression of orally disintegrating
      tablets were compared (Ludiflash, Pharmaburst, F-Melt). The properties of the
      prepared tablets such as tensile strength, friability, wetting time and water
      absorption ratio were evaluated. Disintegration time was measured using the
      pharmacopoeial method and the novel apparatus constructed by the authors. The
      apparatus was based on the idea of Narazaki et al., however it has been modified.
      Magnetic resonance imaging (MRI) was applied for the analysis of the
      disintegration mechanism of prepared tablets. The research has shown the
      significant effect of excipients, compression force, temperature, volume and kind
      of medium on the disintegration process. The novel apparatus features better
      correlation of disintegration time with in vivo results (R(2) = 0.9999) than the
      compendial method (R(2) = 0.5788), and presents additional information on the
      disintegration process, e.g. swelling properties.

PMID- 22881601
TI  - Catalytic electrochemical C-H iodination and one-pot arylation by ON/OFF
      switching of electric current.
AB  - Palladium-catalyzed electrochemical iodination and one-pot arylation of
      arylpyridines are described. Ortho-selective C-H iodination proceeded via dual
      activation of each substrate by a palladium catalyst and an electrode. Various
      aryl groups were introduced at the ortho positions of arylpyridines by ON/OFF
      switching of two different catalytic cycles using the same palladium catalyst in
      a one-pot fashion.

PMID- 22881602
TI  - Multifactorial etiology of interictal behavior in frontal and temporal lobe
      epilepsy.
AB  - PURPOSE: Based on discussions on the so called "epileptic personality" in
      patients with epilepsy, interictal behavioral impairments in frontal and temporal
      lobe epilepsies were examined in a multivariate approach that took demographic,
      clinical, and neuropsychological determinants into consideration. METHODS: A
      total of 428 patients with epilepsies originating from the temporal (TLE; 84%) or
      frontal (FLE; 16%) lobes were examined in regard to personality (Fragebogen zur
      Personlichkeit bei zerebralen Erkrankungen [FPZ], a clinical personality
      questionnaire) and mood (Beck Depression Inventory [BDI I]). Prevalence of
      impaired behavioral domains was determined. Etiologically relevant determinants
      of behavioral problems were identified via multiple regression analyses. KEY
      FINDINGS: Elevated depression scores (BDI) were evident in 42% of the patients,
      and not different in TLE and FLE. In regard to personality, introversion together
      with low mood, sociability, and self-determination, as well as problems with
      interpersonal communication were frequent. The TLE group tended to show greater
      neuroticism and introversion, while FLE appeared more associated with behavioral
      aspects of an organic psychosyndrome. Multivariate analyses revealed demographic
      characteristics (age, gender, education), clinical aspects (psychiatric history,
      affected hemisphere, mesial pathology, seizure frequency, cognitive functions),
      and treatment (antiepileptic drug treatment) as relevant determinants, explaining
      up to 30% of the behavior. SIGNIFICANCE: Behavioral abnormalities in patients
      with frontal or temporal lobe epilepsy are common but on the average mostly mild.
      Within a multivariate etiological model, localization (mesial yes/no) and
      lateralization (left > right) dependent behavioral problems in TLE and FLE seem
      to be overshadowed by other variables, of which patients' and their families'
      psychiatric history, patient characteristics and pharmacological treatment appear
      of major importance. Better education and cognitive capabilities may be discussed
      as protective features.

PMID- 22881603
TI  - State-selected unimolecular decomposition of delta-valerolactam+ and delta
      valerolactam2+ cations: theory and experiment.
AB  - The near threshold photofragmentation pattern of delta-valerolactam(+) and delta
      valerolactam(2)(+) has been recorded combining electron/ion coincidence
      techniques and vacuum ultraviolet synchrotron radiation. The experimental method
      yields the fragment intensity as a function of the internal energy deposited into
      the parent cation, up to 3.1 eV above the first ionization threshold. In
      parallel, ab initio studies on the delta-valerolactam(+) and delta
      valerolactam(2)(+) cations and their ionic and neutral fragmentation products
      have been performed with the aim of determining the isomers of the ionic products
      observed experimentally as well as of their neutral counterparts. These
      computations were performed using the PBE0 exchange-correlation functional and
      the aug-cc-pVDZ basis set. We found good agreement between the calculated
      reaction enthalpies and experimental appearance energies of the ions. More
      generally, our experimental and theoretical results reveal that the fragmentation
      of the ionic species of interest leads to a multitude of neutral and ionic
      fragments, which may be formed after intramolecular isomerization and complex
      decomposition processes. Multistep reaction pathways are expected.

PMID- 22881604
TI  - Development of a peptidase-resistant substrate for single-cell measurement of
      protein kinase B activation.
AB  - An iterative design strategy using three criteria was utilized to develop a
      peptidase-resistant substrate peptide for protein kinase B. Libraries of peptides
      possessing non-native amino acids were screened for time to 50% phosphorylation,
      degradation half-life within a lysate, and appearance of a dominant fragment. The
      lead peptide possessed a half-life of 92 +/- 7 and 16 +/- 2 min in HeLa and LNCaP
      cytosolic lysates, respectively, representing a 4.6- and 2.7-fold lifetime
      improvement over that of the starting peptide. The redesigned peptide possessed a
      4.5-fold improvement in phosphorylation efficiency compared to the starting
      peptide. The same peptide fragments were formed when the lead peptide was
      incubated in a lysate or loaded into single cells although the fragments formed
      in significantly different ratios suggesting that distinct peptidases metabolized
      the peptide in the two preparations. The rate of peptide degradation and
      phosphorylation was on average 0.1 +/- 0.2 zmol pg(-1) s(-1) and 0.04 +/- 0.08
      zmol pg(-1) s(-1), respectively, for single LNCaP cells loaded with 4 +/- 8 MUM
      of peptide. Peptidase-resistant kinase substrates should find widespread utility
      in both lysate-based and single-cell assays of kinase activity.

PMID- 22881605
TI  - Is abnormal 50-g glucose-challenge testing an independent predictor of adverse
      pregnancy outcome?
AB  - OBJECTIVE: To determine whether an abnormal 50-g glucose-challenge test (GCT) is
      independently associated with adverse pregnancy outcome. METHODS: A retrospective
      study of women with abnormal GCT (>140 mg/dL) but normal subsequent 100-g oral
      glucose-tolerance test (OGTT). Pregnancy outcome was compared with that of women
      with normal GCT (<140 mg/dL). RESULTS: Of the 79,153 women delivered during the
      study period, the results of the GCT were available for 14,268. Of these, 809
      (5.7%) had an abnormal GCT and normal OGTT and were eligible for the study group.
      An abnormal GCT was independently associated with an increased risk for
      macrosomia (odds ratio [OR] = 2.0, 95% CI: 1.5-2.7), large for gestational age
      (OR = 1.6, 95% CI: 1.3-2.0), cesarean section (OR = 1.3, 95% CI: 1.1-1.6),
      respiratory morbidity (OR = 1.6, 95% CI: 1.1-2.7) and neonatal hypoglycemia (OR =
      1.8, 95% CI: 1.1-3.2). In contrast, an abnormal GCT was associated with decreased
      risk for preterm delivery at less than 37 weeks (OR = 0.7, 95% CI: 0.5-0.9) and
      34 weeks (OR = 0.3, 95% CI: 0.1-0.6). The association between abnormal GCT and
      adverse pregnancy outcome was unrelated to the degree of GCT abnormality except
      for cases in which the GCT was extremely high (>=180 mg/dL). CONCLUSION: Women
      with abnormal-GCT result are at increased risk for adverse pregnancy outcome even
      in the presence of a normal subsequent OGTT.

PMID- 22881702
TI  - Depletion of deep marine food patches forces divers to give up early.
AB  - Many optimal foraging models for diving animals examine strategies that maximize
      time spent in the foraging zone, assuming that prey acquisition increases
      linearly with search time. Other models have considered the effect of patch
      quality and predict a net energetic benefit if dives where no prey is encountered
      early in the dive are abandoned. For deep divers, however, the energetic benefit
      of giving up is reduced owing to the elevated energy costs associated with
      descending to physiologically hostile depths, so patch residence time should be
      invariant. Others consider an asymptotic gain function where the decision to
      leave a patch is driven by patch-depletion effects - the marginal value theorem.
      As predator behaviour is increasingly being used as an index of marine resource
      density and distribution, it is important to understand the nature of this gain
      function. We investigated the dive behaviour of the world's deepest-diving seal,
      the southern elephant seal Mirounga leonina, in response to patch quality.
      Testing these models has largely been limited to controlled experiments on
      captive animals. By integrating in situ measurements of the seal's relative lipid
      content obtained from drift rate data (a measure of foraging success) with area
      restricted search behaviour identified from first-passage time analysis, we
      identified regions of high- and low-quality patches. Dive durations and bottom
      times were not invariant and did not increase in regions of high quality; rather,
      both were longer when patches were of relatively low quality. This is consistent
      with the predictions of the marginal value theorem and provides support for a
      nonlinear relationship between search time and prey acquisition. We also found
      higher descent and ascent rates in high-quality patches suggesting that seals
      minimized travel time to the foraging patch when quality was high; however, this
      was not achieved by increasing speed or dive angle. Relative body lipid content
      was an important predictor of dive behaviour. Seals did not schedule their diving
      to maximize time spent in the foraging zone in higher-quality patches,
      challenging the widely held view that maximizing time in the foraging zone
      translates to greater foraging success.

PMID- 22881703
TI  - Tip-enhanced Raman detection of antibody conjugated nanoparticles on cellular
      membranes.
AB  - Tip enhanced Raman scattering (TERS) microscopy is used to image antibody
      conjugated nanoparticles on intact cellular membranes. The combination of
      plasmonic coupling and the resultant electric field obtained from intermediate
      focusing of a radially polarized source gives rise to Raman images with spatial
      resolution below 50 nm. Finite element method calculations are used to explain
      the origins of the observed image resolution and spectroscopic signals. The
      observed Raman scattering provides information about the biomolecules present
      near the nanoparticle probes. The results show that aggregates of nanoparticles
      produce spectroscopic results similar to those reported from other surface
      enhanced Raman spectroscopies, e.g., shell isolated nanoparticle enhanced Raman
      spectroscopy (SHINERS) and aggregated nanoparticles; however, TERS enables the
      detection of isolated nanoparticles on cell membranes where the observed spectra
      provide information about the interaction of the specific biomolecule conjugated
      to the nanoparticle probe. These measurements present a new technique for
      exploring biomolecular interactions on the surface of cells and tissue.

PMID- 22881704
TI  - Diastereomer-specific uptake, translocation, and toxicity of
      hexabromocyclododecane diastereoisomers to maize.
AB  - Hexabromocyclododecane (HBCD), a brominated flame retardant, has become a
      ubiquitous contaminant due to its wide application, persistence, and toxicity.
      HBCD diastereoisomers have different physical and chemical properties and may
      differ in their bioaccumulation and toxicity in plants. Accumulation and toxicity
      of alpha-, beta-, and gamma-HBCDs in maize were investigated in the present
      study. The accumulation was in the order beta-HBCD > alpha-HBCD > gamma-HBCD in
      roots and beta-HBCD > gamma-HBCD > alpha-HBCD in shoots. Both the inhibitory
      effect of the diastereoisomers on the early development of maize and the
      intensities of hydroxyl radical and histone H2AX phosphorylation in maize exposed
      to 2 MUg L(-1) HBCD followed the order alpha-HBCD > beta-HBCD > gamma-HBCD,
      indicating the diastereomer-specific oxidative stress and DNA damage in maize. It
      was further confirmed that the generation of reactive oxygen species was one, but
      not the only, mechanism for DNA damage in maize exposed to HBCDs. 

PMID- 22881705
TI  - Overall self-perceived health in Restless legs treated with intrathecal morphine.
AB  - OBJECTIVES: Restless legs syndrome (RLS) has a high prevalence in the general
      population. Treatment with intrathecal morphine has been shown to be successful
      in a small number of patients. Our aim was to quantify the effect on RLS-related
      symptoms, health and quality of life in three patients treated with intrathecal
      morphine. MATERIALS AND METHODS: Three patients with medically refractory RLS
      received an implanted pump for delivery of intrathecal morphine. Severity of RLS
      and self-assessed health were rated using the International Restless Legs
      Syndrome Study Group (IRLSSG) rating scale and the Short Form health survey (SF
      36). Assessments were made preoperatively and after 6 months of follow-up.
      RESULTS: Preoperatively two patients had very severe RLS, scoring 35 and 36 on
      the IRLSSG rating scale, and one patient had severe RLS (score, 26). All three
      patients were free of symptoms of RLS post-operatively and also at the 6-month
      follow-up. The daily doses of intrathecal morphine ranged from 73 to 199 ug.
      Results from the SF-36 health survey showed that all three patients had a better
      physical health compared to before surgery. CONCLUSION: Intrathecal morphine may
      be efficient in the treatment for medically refractory RLS. All three patients
      became completely free of symptoms, and there was also improvement in self
      perceived overall health.

PMID- 22881706
TI  - Motivational interviewing training to promote Head Start children's adherence to
      oral health care recommendations: results of a program evaluation.
AB  - OBJECTIVES: Motivational interviewing (MI) is a research-supported, patient
      centered counseling technique to support health behavior change. We evaluated
      training to help teachers use MI for oral health promotion in a multi-site,
      diverse, urban Head Start organization. METHODS: MI training was evaluated based
      on the intervention's reach, effectiveness, adoption, implementation, and
      maintenance. RESULTS: MI was introduced to 150 Head Start staff and 32 received
      intensive training. Trainees had greater knowledge and willingness to use MI 6
      months after training than non-trained staff, and reported increased use of MI
      consistent counseling techniques. Additionally, the rate of completed dental
      visits improved slightly across all families served by this Head Start program
      after teachers used MI with a subset of families. Maintenance is likely based on
      ongoing organizational interest. CONCLUSIONS: Trainees reported successfully
      using MI techniques in this community-based educational setting. Additional
      efforts are needed to increase the reach of training and to ensure
      sustainability.

PMID- 22881708
TI  - Spatially refined aerosol direct radiative forcing efficiencies.
AB  - Global aerosol direct radiative forcing (DRF) is an important metric for
      assessing potential climate impacts of future emissions changes. However, the
      radiative consequences of emissions perturbations are not readily quantified nor
      well understood at the level of detail necessary to assess realistic policy
      options. To address this challenge, here we show how adjoint model sensitivities
      can be used to provide highly spatially resolved estimates of the DRF from
      emissions of black carbon (BC), primary organic carbon (OC), sulfur dioxide
      (SO(2)), and ammonia (NH(3)), using the example of emissions from each sector and
      country following multiple Representative Concentration Pathway (RCPs). The
      radiative forcing efficiencies of many individual emissions are found to differ
      considerably from regional or sectoral averages for NH(3), SO(2) from the power
      sector, and BC from domestic, industrial, transportation and biomass burning
      sources. Consequently, the amount of emissions controls required to attain a
      specific DRF varies at intracontinental scales by up to a factor of 4. These
      results thus demonstrate both a need and means for incorporating spatially
      refined aerosol DRF into analysis of future emissions scenario and design of air
      quality and climate change mitigation policies.

PMID- 22881707
TI  - Diagnosing delirium in older hospitalized adults with dementia: adapting the
      confusion assessment method to international classification of diseases, tenth
      revision, diagnostic criteria.
AB  - OBJECTIVES: To compare performance characteristics of the Confusion Assessment
      Method (CAM) algorithm for screening and delirium diagnosis with criteria for
      delirium from the International Classification of Diseases, Tenth Revision (ICD
      10) and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV) in high-risk individuals. DESIGN: Prospective cohort study. SETTING:
      Academic geriatric hospital. PARTICIPANTS: One hundred two individuals aged 80 to
      100 hospitalized for acute medical illness. MEASUREMENTS: Complete CAM instrument
      (nine items), scored using the four-item CAM diagnostic algorithm. Criterion
      standard classification of delirium was rated independently according to expert
      consensus based on DSM-IV and ICD-10 criteria for delirium. RESULTS: In 79
      hospitalized participants, the CAM performed well for delirium screening
      (delirium prevalence of 24% according to DSM-IV and 14% according to ICD-10). Of
      all CAM features, acute onset and fluctuating course are most important for
      diagnosis (area under the receiver operating characteristic curve (AUC) = 0.92 in
      DSM-IV and 0.83 in ICD-10). The CAM diagnostic algorithm had a sensitivity of
      0.74, a specificity of 1.0, and an AUC of 0.88 compared with the DSM-IV reference
      standard and a sensitivity of 0.82, a specificity of 0.91, and an AUC of 0.85
      compared with the ICD-10. Compared with the ICD-10, adding psychomotor change to
      the CAM algorithm improved specificity to 97%, but sensitivity fell to 55% (AUC =
      0.96). Applying psychomotor change sequentially only to the group that the CAM
      algorithm identified as having no delirium improved sensitivity to 91% with
      specificity of 85% (AUC = 0.95). CONCLUSION: Although the CAM diagnostic
      algorithm performed well against a DSM-IV reference standard, adding psychomotor
      change to the CAM algorithm improved specificity and diagnostic value against ICD
      10 criteria overall in older adults with dementia and improved sensitivity and
      screening performance when applied sequentially in CAM-negative individuals.

PMID- 22881709
TI  - Hereditary hyperferritinemia cataract syndrome in four patients with mutations in
      the IRE of the FTL gene.

PMID- 22881711
TI  - Spontaneous exstrophy-epispadias complex in a goat-kid.

PMID- 22881712
TI  - MY (Matsubara-Yano) uterine compression suture to prevent acute recurrence of
      uterine inversion.

PMID- 22881710
TI  - Endosomal proteolysis regulates calcitonin gene-related peptide responses in
      mesenteric arteries.
AB  - BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is a potent
      vasodilator, implicated in the pathogenesis of migraine. CGRP activates a
      receptor complex comprising, calcitonin receptor-like receptor (CLR) and receptor
      activity-modifying protein 1 (RAMP1). In vitro studies indicate recycling of
      CLR?RAMP1 is regulated by degradation of CGRP in early endosomes by endothelin
      converting enzyme-1 (ECE-1). However, it is not known if ECE-1 regulates the
      resensitization of CGRP-induced responses in functional arterial tissue.
      EXPERIMENTAL APPROACH: CLR, ECE-1a-d and RAMP1 expression in rat mesenteric
      artery smooth muscle cells (RMA-SMCs) and mesenteric arteries was analysed by RT
      PCR and by immunofluorescence and confocal microscopy. CGRP-induced signalling in
      cells was examined by measuring cAMP production and ERK activation. CGRP-induced
      relaxation of arteries was measured by isometric wire myography. ECE-1 was
      inhibited using the specific inhibitor, SM-19712. KEY RESULTS: RMA-SMCs and
      arteries contained mRNA for CLR, ECE-1a-d and RAMP1. ECE-1 was present in early
      endosomes of RMA-SMCs and in the smooth muscle layer of arteries. CGRP induced
      endothelium-independent relaxation of arteries. ECE-1 inhibition had no effect on
      initial CGRP-induced responses but reduced cAMP generation in RMA-SMCs and
      vasodilation in mesenteric arteries responses to subsequent CGRP challenges.
      CONCLUSIONS AND IMPLICATIONS: ECE-1 regulated the resensitization of responses to
      CGRP in RMA-SMCs and mesenteric arteries. CGRP-induced relaxation did not involve
      endothelium-derived pathways. This is the first report of ECE-1 regulating CGRP
      responses in SMCs and arteries. ECE-1 inhibitors may attenuate an important
      vasodilatory pathway, implicated in primary headaches and may represent a new
      therapeutic approach for the treatment of migraine.

PMID- 22881713
TI  - Biodegradable scaffold fabricated of electrospun albumin fibers: mechanical and
      biological characterization.
AB  - Natural polymers share recognition sequences that promote cell adhesion,
      rendering them attractive candidates for scaffolding in tissue engineering
      applications. However, challenges remain with regard to the fabrication of robust
      and porous structures of such raw materials for the design of extracellular
      matrix (ECM) mimics of living tissues. In this study, we present a fibrous
      scaffold that solely consists of albumin, the most abundant protein in mammalian
      blood plasma. The scaffold was fabricated using the electrospinning method, and
      resulted in microscale fibers that demonstrated mechanical properties which were
      similar to those of elastin fibers, a common component of connective tissue ECM.
      Albumin scaffolds proved nontoxic and supported adhesion and the spreading of
      fibroblasts, muscle cells, and endothelial cells (ECs) in vitro. In vivo studies
      demonstrated ~50% biodegradation of the albumin scaffolds within 3 weeks of
      implantation. In addition, it was found that the fibers were encapsulated by
      dense fibrosis and evoked a weak inflammatory response, similar to that triggered
      by poly(L-lactide)/poly(lactic-co-glycolic acid) scaffolds. Albumin tubular
      structures fabricated to mimic blood vessels successfully guided the formation of
      blood vessel-like bi-layer structures made of fibroblasts and ECs. Thus, albumin
      scaffolds featuring biologically relevant characteristics pose a readily
      applicable alternative to synthetic scaffolding materials.

PMID- 22881714
TI  - Reconstitution studies of pesticides and surfactants exploring the cause of
      estrogenic activity observed in surface waters of the San Francisco Bay Delta.
AB  - To evaluate the potential role of endocrine disruption in the decline of pelagic
      fishes in the San Francisco Bay Delta of California, various surface water
      samples were collected, extracted, and found to elicit estrogenic activity in
      laboratory fish. Chemical analysis of the estrogenic samples indicated 2
      pesticides (bifenthrin, diuron), 2 alkyphenols (AP), and mixtures of 2 types of
      alkyphenol polyethoxylates (APEOs). Evaluation of estrogenic activity was further
      characterized by in vitro bioassays using rainbow trout hepatocytes (Oncorhynchus
      mykiss) and in vivo studies with Japanese medaka (Oryzias latipes). In the in
      vitro bioassays, hepatocytes exposed to the pesticides alone or in combination
      with the AP/APEO mixtures at concentrations observed in surface waters failed to
      show estrogenic activity (induction of vitelloginin mRNA). In the in vivo
      bioassays, medaka exposed to individual pesticides or to AP/APEO alone did not
      have elevated VTG at ambient concentrations. However, when the pesticides were
      combined with AP/APEOs in the 7-day exposure a significant increase in VTG was
      observed. Exposure to a 5-fold higher concentration of the AP/APEO mixture alone
      also significantly induced VTG. In contrast to earlier studies with permethrin,
      biotransformation of bifenthrin to estrogenic metabolites was not observed in
      medaka liver microsomes and cytochrome P450 was not induced with AP/APEO
      treatment. These results showed that mixtures of pesticides with significantly
      different modes of action and AP/APEOs at environmentally relevant concentrations
      may be associated with estrogenic activity measured in water extracts and feral
      fish that have been shown to be in population decline in the San Francisco Bay
      Delta.

PMID- 22881715
TI  - Synthesis and characterization of RNA containing a rigid and nonperturbing
      cytidine-derived spin label.
AB  - The nitroxide-containing nucleoside Cm is reported as the first rigid spin label
      for paramagnetic modification of RNA by solid-phase synthesis. The spin label is
      well accommodated in several RNA secondary structures as judged by its minor
      effect on the thermodynamic stability of hairpin and duplex RNA. Electron
      paramagnetic resonance (EPR) spectroscopic characterization of mono-, bi-, and
      trimolecular RNA structures shows that Cm will be applicable for advanced EPR
      studies to elucidate structural and dynamic aspects of folded RNA.

PMID- 22881717
TI  - A rare case of congenital choroid plexus carcinoma.
AB  - We report a 1-year-old child with the prenatal (week 29 + 5) diagnosis of a brain
      tumor. The parents were informed about all aspects of prognosis and options
      concerning termination of pregnancy. The parents opted for an aggressive
      therapeutic approach after extensive and informative case conferences and
      counseling. The histopathological diagnosis after partial tumor resection was
      choroid plexus carcinoma, two weeks thereafter tumor size was progressive. The
      parents opted for palliative treatment at this stage. The patient died at the age
      of one year. Ethical aspects have to be actively considered and addressed when
      caring for children with choroid plexus carcinoma.

PMID- 22881716
TI  - Naturally occurring variation in the Glutathione-S-Transferase 4 gene determines
      neurodegeneration after traumatic brain injury.
AB  - AIM: Genetic factors are important for outcome after traumatic brain injury
      (TBI), although exact knowledge of relevant genes/pathways is still lacking. We
      here used an unbiased approach to define differentially activated pathways
      between the inbred DA and PVG rat strains. The results prompted us to study
      further if a naturally occurring genetic variation in glutathione-S-transferase
      alpha 4 (Gsta4) affects the outcome after TBI. RESULTS: Survival of neurons after
      experimental TBI is increased in PVG compared to the DA strain. Global expression
      profiling analysis shows the glutathione metabolism pathway to be the most
      regulated between the strains, with increased Gsta4 in PVG among top regulated
      transcripts. A congenic strain (R5) with a PVG genomic insert containing the
      Gsta4 gene on DA background displays a reversal of the strain pattern for Gsta4
      expression and increased survival of neurons compared to DA. Gsta4 is known to
      effectively reduce 4-hydroxynonenal (4-HNE), a noxious by-product of lipid
      peroxidation. Immunostaining of 4-HNE was evident in both rat and human TBI.
      Intracerebral injection of 4-HNE resulted in neurodegeneration with increased
      levels of a marker for nerve injury in cerebrospinal fluid of DA compared to R5.
      INNOVATION: These findings provide strong support for the notion that the
      inherent capability of coping with increased 4-HNE after TBI affects outcome in
      terms of nerve cell loss. CONCLUSION: A naturally occurring variation in Gsta4
      expression in rats affects neurodegeneration after TBI. Further studies are
      needed to explore if genetic variability in Gsta4 can be associated to outcome
      also in human TBI.

PMID- 22881718
TI  - Adrenomedullin alterations related to cardiopulmonary bypass in infants with low
      cardiac output syndrome.
AB  - BACKGROUND: Low cardiac output syndrome (LCOS) remains a major perioperative
      complications in infants subjected to open-heart surgery with cardiopulmonary
      bypass (CPB). The present study investigated whether perioperative blood
      assessment of a potent vasoactive peptide namely adrenomedullin (AM) can predict
      the risk of LCOS. METHODS: We measured AM levels in 48 patients (LCOS: n = 9;
      controls: n = 39) undergone to open-heart surgery with CPB at five predetermined
      time points before, during and after the surgery. Clinical, laboratory and
      perioperative data were analyzed by a multiple logistic regression model.
      RESULTS: AM significantly decreased (p < 0.01) during and after the surgical
      procedure exhibiting a dip at the end of the CPB. Multivariable analysis
      demonstrated significant correlations among LCOS, AM measured at the end of CPB
      (p < 0.001), and cooling duration (p < 0.05). AM at 27 pg/L cutoff achieved a
      sensitivity of 100% and a specificity of 64.1%, while cooling at 11-min cutoff
      combined a sensitivity of 55.6% and a specificity of 92.3% for LCOS prediction.
      CONCLUSIONS: This study suggests that AM can constitute, alone or combined with
      standard parameters, a promising predictor of LCOS in infants subjected to open
      heart surgery with CPB.

PMID- 22881719
TI  - Quantitative real-time monitoring of chemical reactions by autosampling flow
      injection analysis coupled with atmospheric pressure chemical ionization mass
      spectrometry.
AB  - Although qualitative and/or semiquantitative real-time monitoring of chemical
      reactions have been reported with a few mass spectrometric approaches, to our
      knowledge, no quantitative mass spectrometric approach has been reported so far
      to have a calibration valid up to molar concentrations as required by process
      control. This is mostly due to the absence of a practical solution that could
      well address the sample overloading issue. In this study, a novel autosampling
      flow injection analysis coupled with an atmospheric pressure chemical ionization
      mass spectrometry (FIA/APCI-MS) system, consisting of a 1 MUL automatic internal
      sample injector, a postinjection splitter with 1:10 splitting ratio, and a
      detached APCI source connected to the mass spectrometer using a 4.5 in. long,
      0.042 in. inner diameter (ID) stainless-steel capillary, was thus introduced.
      Using this system together with an optional FIA solvent modifier, e.g., 0.05%
      (v/v) isopropylamine, a linear quantitative calibration up to molar concentration
      has been achieved with 3.4-7.2% relative standard deviations (RSDs) for 4
      replicates. As a result, quantitative real-time monitoring of a model reaction
      was successfully performed at the 1.63 M level. It is expected that this novel
      autosampling FIA/APCI-MS system can be used in quantitative real-time monitoring
      of a wide range of reactions under diverse reaction conditions.

PMID- 22881720
TI  - Synthesis and preclinical evaluation of bifunctional ligands for improved
      chelation chemistry of 90Y and 177Lu for targeted radioimmunotherapy.
AB  - We report a practical and high-yield synthesis of a bimodal bifunctional ligand
      3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor
      targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody,
      trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated
      and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA,
      C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with (90)Y and (177)Lu. 3p-C
      NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with
      (90)Y and (177)Lu. (90)Y-3p-C-NETA-trastuzumab and (177)Lu-3p-C-NETA-trastuzumab
      conjugates were stable in human serum for 2 weeks. A pilot biodistribution study
      was conducted to evaluate in vivo stability and tumor targeting of (177)Lu
      radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast
      cancer. (177)Lu-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level
      at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at
      120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an
      excellent bifunctional chelator that can be used for targeted RIT applications
      using (90)Y and (177)Lu and has the potential to replace DOTA and DTPA analogues
      in current clinical use.

PMID- 22881826
TI  - rTMS as a treatment for neurogenic communication and swallowing disorders.
AB  - Recent years have seen the introduction of non-invasive brain stimulation
      techniques (e.g. transcranial direct current stimulation and transcranial
      magnetic stimulation) utilized to target neural-based pathologies, for
      therapeutic gain. The direct manipulation of cortical brain activity by
      repetitive transcranial magnetic stimulation (rTMS) could potentially serve as an
      efficacious complimentary rehabilitatory treatment for speech, language and
      swallowing disorders of a neurological origin. The high prevalence of positive
      reports on communication and swallowing outcomes support these premises.
      Nonetheless, experimental evidence to date in some areas is considered
      rudimentary and is deficient in providing placebo-controlled substantiation of
      longitudinal neuroplastic change subsequent to stimulation. The most affirmative
      therapeutic responses have arisen from small placebo-controlled trials using low
      frequency rTMS for patients with non-fluent aphasia and high-frequency rTMS
      applied to individuals with Parkinson's disease to improve motor speech
      performance and outcomes. Preliminary studies applying rTMS to ameliorate
      dysphagic symptoms post-stroke provide positive swallowing outcomes for patients.
      Further research into the optimization of rTMS protocols, including dosage,
      stimulation targets for maximal efficacy and placebo techniques, is critically
      needed to provide a fundamental basis for clinical interventions using this
      technique. rTMS represents a highly promising and clinically relevant technique,
      warranting the future development of clinical trials across a spectrum of
      communication and swallowing pathologies, to substantiate and expand on the
      methods outlined in published reports.

PMID- 22881827
TI  - An experimental test of differential susceptibility to parenting among
      emotionally-dysregulated children in a randomized controlled trial for
      oppositional behavior.
AB  - BACKGROUND: The concept of differential susceptibility has challenged the
      potential meaning of personal traits such as poor ability to regulate emotions.
      Under the traditional model of diathesis/stress, personal characteristics such as
      liability to angry outbursts are seen as essentially disadvantageous, emerging
      under duress in a way that is maladaptive. In contrast, with differential
      susceptibility, there is the same poorer functioning under adverse conditions
      but, under favorable conditions, individuals with the trait function better than
      those without it. To date, there have been limited studies on response under
      positive environments. We used the experimental power of an intervention trial to
      test the differential susceptibility hypothesis that children with emotional
      dysregulation would show greater response to an experimentally induced
      improvement in their parenting environment. METHODS: Data were from the SPOKES
      trial (ISRCTN 77566446), a randomized controlled trial of 112 school children who
      were 5-6-years old, screened for elevated levels of oppositionality, randomized
      to parenting groups or control; 109 (97%) were followed-up a year later. Using
      DSM-IV oppositional-defiant symptoms, children were divided into an Emotionally
      Dysregulated type (ED, n = 68) and a Headstrong type (n = 44). The parenting
      intervention was the Incredible Years program supplemented by positive strategies
      to use when reading with children. Assessment of conduct problems and parenting
      was by semistructured interviews. RESULTS: At follow-up, parents of Emotionally
      Dysregulated and Headstrong children allocated to the intervention showed
      significant improvements in their parenting strategies to an equal extent
      compared to parents in the control group. However, the Emotionally-Dysregulated
      children showed a significantly greater decrease in conduct problems between
      intervention and control groups (treatment effect-size 0.84 standard deviations)
      than the Headstrong (es 0.20 SD), p = 0.04. CONCLUSIONS: Using the power of a
      controlled experiment, this study showed that children who exhibited Emotionally
      Dysregulated behavior pretreatment were more responsive to improvements in
      parental care that were experimentally induced. The findings extend prior work on
      differential sensitivity in suggesting that children exhibiting irascibility and
      emotionality may show greater susceptibility to the caregiving environment, and
      may identify a subset of children who respond better to existing treatments.

PMID- 22881828
TI  - Spectroscopy and calculations for 4f(N) -> 4f(N-1)5d transitions of lanthanide
      ions in K3YF6.
AB  - In the present work, we report on the combined experimental and theoretical
      studies of the 4f-5d spectra of Ce(3+), Pr(3+), Nd(3+), Eu(3+), Gd(3+), Tb(3+),
      Dy(3+), and Er(3+) ions in a newly synthesized K3YF6 matrix. The low temperature
      experimental 4f-5d excitation spectra have been analyzed and compared with the
      results of the energy-level and intensity calculations. For this theoretical
      analysis, the extended phenomenological crystal-field model for the 4f(N-1)5d
      configuration (i.e., the extended f-shell programs, developed by Prof. M. F.
      Reid) and exchange charge model (developed by Prof. B. Z. Malkin) have been used
      together to estimate the crystal field parameters and implement the spectral
      simulations. On the basis of the results of the performed theoretical analysis,
      we suggest the most probable positions occupied by optically active ions.
      Although the spectra of only eight lanthanide ions have been studied, the
      Hamiltonian parameters of the 4f(N-1)5d configuration have been evaluated for the
      whole lanthanide series and reported here for the first time, to give a complete
      and unified description of the spectroscopic properties of the trivalent rare
      earth ions in the chosen host. In addition to the studies of the 4f-5d
      transitions, various possible competitive excitation channels overlapping with 4f
      5d ones have also been discussed, where a theoretical scheme giving rudiments to
      understand 4f-6s spectra are proposed for the first time. An excellent agreement
      between the calculated and measured excitation spectra shapes confirms validity
      of the performed analysis. The obtained parameters of the crystal field
      Hamiltonians for different ions and various electron configurations can be used
      in a straightforward way to generate the energy level positions and calculate the
      particular transition intensities for any rare earth ion in any particular
      spectral region. With the aid of the obtained parameters, the positions of the
      lowest energy levels of the 4f(N), 4f(N-1)5d ,and 4f(N-1)6s configurations of
      rare earth ions and 4f(N+1)(np)(5) configuration of rare earth ions and ligands
      (corresponding to the ligand-impurity ion charge transfer transitions) in the
      band gap of K3YF6 have all been estimated. The obtained Hamiltonian parameters
      and energy levels diagrams, which include the electronic structure of a host
      material, can be used as a starting point for analysis of spectroscopic
      properties of trivalent lanthanides in similar fluorides. 

PMID- 22881825
TI  - Battery-free radio frequency identification (RFID) sensors for food quality and
      safety.
AB  - Market demands for new sensors for food quality and safety stimulate the
      development of new sensing technologies that can provide an unobtrusive sensor
      form, battery-free operation, and minimal sensor cost. Intelligent labeling of
      food products to indicate and report their freshness and other conditions is one
      important possible application of such new sensors. This study applied passive
      (battery-free) radio frequency identification (RFID) sensors for the highly
      sensitive and selective detection of food freshness and bacterial growth. In
      these sensors, the electric field generated in the RFID sensor antenna extends
      from the plane of the RFID sensor and is affected by the ambient environment,
      providing the opportunity for sensing. This environment may be in the form of a
      food sample within the electric field of the sensing region or a sensing film
      deposited onto the sensor antenna. Examples of applications include monitoring of
      milk freshness, fish freshness, and bacterial growth in a solution. Unlike other
      food freshness monitoring approaches that require a thin film battery for
      operation of an RFID sensor and fabrication of custom-made sensors, the passive
      RFID sensing approach developed here combines the advantages of both battery-free
      and cost-effective sensor design and offers response selectivity that is
      impossible to achieve with other individual sensors.

PMID- 22881829
TI  - Different refractive errors in triplets with retinopathy of prematurity treated
      with bevacizumab.
AB  - The authors report refractive errors possibly resulting from intravitreal
      bevacizumab injection. Triplet A presented with stage 3 retinopathy of
      prematurity, was treated with intravitreal bevacizumab, and high refractive
      errors were noted. Triplet B presented with stage 2 retinopathy of prematurity in
      the right eye and stage 3 retinopathy of prematurity in the left eye, which
      regressed spontaneously. Triplet C presented with stage 2 retinopathy of
      prematurity in the right eye and stage 3 retinopathy of prematurity in the left
      eye, which were treated with intravitreal bevacizumab.

PMID- 22881830
TI  - A case of internal ophthalmoplegia associated with varicella zoster.
AB  - The authors report a case of internal ophthalmoplegia in a 5-year-old boy
      presenting after primary varicella infection. This is an uncommon and mostly
      irreversible ocular manifestation after chickenpox. The internal ophthalmoplegia
      showed a potential mild improvement with oral acyclovir. Consideration should be
      given to starting treatment on presentation in such cases.

PMID- 22881831
TI  - Duane retraction syndrome with posterior microphthalmos: a rare association.
AB  - Duane retraction syndrome is known to be associated with numerous ocular and
      systemic anomalies. The authors describe a 7-year-old child with unilateral Duane
      retraction syndrome type 1 with bilateral posterior microphthalmos. To the best
      of the authors' knowledge, this is the first reported coexistence of Duane
      retraction syndrome with posterior microphthalmos.

PMID- 22881832
TI  - Aerobic denitration of 2,4,6-trinitrotoluene in the presence of phenazine
      compounds and reduced pyridine nucleotides.
AB  - Phenazine-containing spent culture supernatants of Pseudomonas aeruginosa
      concentrated with a C18 solid-phase extraction cartridge initiate NAD(P)H
      dependent denitration of 2,4,6-trinitrotoluene (TNT). In this study, TNT
      denitration was investigated under aerobic conditions using two phenazine
      secondary metabolites excreted by P. aeruginosa, pyocyanin (Py) and its precursor
      phenazine-1- carboxylic acid (PCA), and two chemically synthesized pyocyanin
      analogs, phenazine methosulfate (PMS+) and phenazine ethosulfate (PES+). The
      biomimetic Py/NAD(P)H/O2 system was characterized and found to extensively
      denitrate TNT in unbuffered aqueous solution with minor production of toxic amino
      aromatic derivatives. To a much lesser extent, TNT denitration was also observed
      with PMS+ and PES+ in the presence of NAD(P)H. No TNT denitration was detected
      with the biomimetic PCA/NAD(P)H/O2 system. Electron paramagnetic resonance (EPR)
      spectroscopy analysis of the biomimetic Py/NAD(P)H/O2 system revealed the
      generation of superoxide radical anions (O2 *-). In vitro TNT degradation
      experiments in the presence of specific inhibitors of reactive oxygen species
      suggest a nucleophilic attack of superoxide radical anion followed by TNT
      denitration through an as yet unknown mechanism. The results of this research
      confirm the high functional versatility of the redox-active metabolite pyocyanin
      and the susceptibility of aromatic compounds bearing electron withdrawing
      substituents, such as nitro groups, to superoxide-driven nucleophilic attack.

PMID- 22881833
TI  - The reporting of race and ethnicity information in the dental public health
      literature.
AB  - OBJECTIVES: To document how race and ethnicity are identified, categorized, and
      utilized in contemporary dental public health literature. METHODS: Two
      researchers independently performed a literature review of all articles in
      Community Dentistry and Oral Epidemiology and the Journal of Public Health
      Dentistry over a 5-year period (2004-2009). Articles pertaining to the study of
      US-based populations with any mention of race or ethnicity were included. The
      following data were abstracted from each article:( a) how each article broadly
      described race and/or ethnicity; (b) the terms used to specifically define the
      races and/or ethnicities captured; (c) the location of any mention of the concept
      of race and/or ethnicity; (d) the stated purpose for including race and/or
      ethnicity concepts; (e) the stated analytic use of race and/or ethnicity
      concepts; and (f) the stated method used to assess race and/or ethnicity
      concepts. RESULTS: Overall, race and/or ethnicity concepts were most commonly
      referred to within the text of the results section. Fifty percent of articles did
      not state their purpose for including race and/or ethnicity concepts within their
      studies, while 34.3 percent omitted stating their analytic use of these concepts.
      When assessing these concepts, 41.4 percent relied upon subject self-report.
      CONCLUSION: These data showed that there was inconsistent documentation of how
      race and ethnicity was measured. While race and ethnicity are important measures
      for public health studies and are frequently reported in dental public health
      research, there is no clear system for classifying these measures.

PMID- 22881834
TI  - Quantum junction solar cells.
AB  - Colloidal quantum dot solids combine convenient solution-processing with quantum
      size effect tuning, offering avenues to high-efficiency multijunction cells based
      on a single materials synthesis and processing platform. The highest-performing
      colloidal quantum dot rectifying devices reported to date have relied on a
      junction between a quantum-tuned absorber and a bulk material (e.g., TiO(2));
      however, quantum tuning of the absorber then requires complete redesign of the
      bulk acceptor, compromising the benefits of facile quantum tuning. Here we report
      rectifying junctions constructed entirely using inherently band-aligned quantum
      tuned materials. Realizing these quantum junction diodes relied upon the creation
      of an n-type quantum dot solid having a clean bandgap. We combine stable,
      chemically compatible, high-performance n-type and p-type materials to create the
      first quantum junction solar cells. We present a family of photovoltaic devices
      having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum
      to-bulk devices fail to perform. Devices having optimal single-junction bandgaps
      exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over
      doping in quantum solids, and the successful integration of these materials to
      form stable quantum junctions, offers a powerful new degree of freedom to
      colloidal quantum dot optoelectronics.

PMID- 22881835
TI  - Unmasking Hb Pakse (codon 142, TAA>TAT, alpha2) and its combinations in patients
      also carrying Hb Constant Spring (codon 142, TAA>CAA, alpha2) in northern
      Thailand.
AB  - The incidence of Hb Pakse (codon 142, TAA>TAT, alpha2) might have been
      underestimated due to misidentifying some cases as Hb Constant Spring (Hb CS,
      codon 142, TAA>CAA, alpha2) since both abnormal hemoglobins (Hbs) migrate to the
      same position on Hb electrophoresis or chromatography. Multiplex asymmetric
      allele-specific polymerase chain reaction (PCR) for identification of Hb CS and
      Hb Pakse, and a real-time PCR (ReTi-PCR) with SYBR Green1 high resolution melting
      (HRM) analysis, for detection of the alpha-thalassemia-1 (alpha-thal-1) Southeast
      Asian (- -(SEA)/) type deletion, were performed on 114 blood samples collected
      from subjects who lived in northern Thailand. These samples were previously
      identified as carrying Hb CS by capillary electrophoresis (CE) or high
      performance liquid chromatography (HPLC). Five out of 114 (4.4%) samples were
      found to carry Hb Pakse with four different genotypes including Hb Pakse trait,
      compound Hb CS/Hb Pakse, Hb H-Hb Pakse disease and Hb H-Hb Pakse-Hb E disease.
      These results suggested that Hb Pakse and its various combinations can be
      misidentified as Hb CS. Although the clinical symptoms of Hb Pakse and Hb CS are
      similar, to prevent erroneous epidemiological data on Hb CS as well as
      underestimating the prevalence of Hb Pakse in northern Thailand, DNA analysis is
      recommended to be performed in all cases when peaks of Hb CS/Hb Pakse are
      detected on CE or HPLC.

PMID- 22881836
TI  - Genetic variation in dopaminergic activity is associated with the risk for
      psychiatric side effects of levetiracetam.
AB  - PURPOSE: Levetiracetam (LEV) is a highly effective antiepileptic agent. A
      clinically relevant psychiatric complication of LEV treatment, however, is the
      provocation of irritability and aggression. Recent behavioral research indicates
      that personality traits may predispose to these side effects. To assess the
      genetic basis of the adverse psychotropic profile of LEV, a candidate gene-based
      two-stage association study was conducted. METHODS: Polymorphisms were a priori
      selected according to their relevance for impulsivity and reactive-impulsive
      aggression. Based on data from both stages, a Bonferroni-corrected joint meta
      analysis was computed. KEY FINDINGS: Stage 1 analysis included 290 patients with
      epilepsy and revealed a higher load of adverse psychotropic side effects of LEV
      in patients carrying genetic variants associated with decreased dopaminergic
      activity: rs1611115 (dopamine-beta-hydroxylase, DBH), rs4680 (catechol-O
      methyltransferase, COMT), and rs1800497 (dopamine receptor D2-associated ANKK1
      TAQ-1A). Stage II analysis including 100 patients with epilepsy, and joint meta
      analysis confirmed the effect of the rs1800497 polymorphism (Bonferroni corrected
      significance of the joint meta-analysis, p = 0.0096). SIGNIFICANCE: Confirming
      the suggestion from behavioral observations that patients might be predisposed to
      develop irritation and aggression under treatment with LEV, the findings provide
      first evidence of an association of genetic variation in dopaminergic activity
      and the risk for psychiatric complications of LEV treatment. Replication and
      further work is required to prove a true causal relationship. Overall, the
      pharmacogenomic approach to behavioral side effects may provide a future tool to
      predict adverse psychotropic effects related to antiepileptic drugs.

PMID- 22881838
TI  - The novel NOX inhibitor 2-acetylphenothiazine impairs collagen-dependent thrombus
      formation in a GPVI-dependent manner.
AB  - BACKGROUND AND PURPOSE: NADPH oxidases (NOXs) contribute to platelet activation
      by a largely unknown mechanism. Here, we studied the effect of the novel NOX
      inhibitor 2-acetylphenothiazine (2-APT) on human platelet functional responses
      and intracellular signaling pathways. EXPERIMENTAL APPROACH: The generation of
      superoxide ions was assessed by single cell imaging on adhering platelets using
      dihydroethidium (DHE), while other reactive oxygen species (ROS) were detected
      with 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CM-H(2)
      DCFDA). Whole blood thrombus formation, washed platelet aggregation, integrin
      alphaIIbbeta3 inside-out signalling, Syk phosphorylation and PKC activation were
      analysed to understand the functional consequences of NOX inhibition by 2-APT in
      platelets. KEY RESULTS: Superoxide ion generation stimulated by platelet adhesion
      on collagen and fibrinogen was significantly inhibited by 2-APT in concentration
      dependent manner (IC(50) = 306 nM and 227 nM, respectively), whereas cumulative
      ROS accumulation was not affected by this pharmacological agent. 2-APT also
      abolished collagen-dependent whole blood thrombus formation and washed platelet
      aggregation in response to collagen but not thrombin. The activation of integrin
      alphaIIbbeta3 and PKC in response to the GPVI-specific agonist collagen-related
      peptide (CRP) was significantly reduced, whereas the same responses to thrombin
      were not significantly affected by 2-APT. Finally, Syk activation in response to
      collagen but not thrombin was inhibited by 2-APT. CONCLUSIONS AND IMPLICATIONS:
      Taken together, our results suggest that 2-APT attenuates GPVI-specific
      signalling and is a novel inhibitor of collagen-induced platelet responses.
      Therefore, NOXs could represent a novel target for the discovery of anti
      thrombotic drugs.

PMID- 22881840
TI  - Use of fetal analgesia during prenatal surgery.
AB  - OBJECTIVE: Recent progresses in fetal surgery have raised concern on fetal pain,
      its long-term consequences and the risks of sudden fetal movements induced by
      pain. In several studies, surgeons have directly administered opioids to the
      fetus, while others have considered sufficient the maternally administered
      analgesics. We performed a review of the literature to assess the state of the
      art. METHODS: We performed a PubMed search to retrieve the papers that in the
      last 10 years reported studies of human fetal surgery and that described whether
      any fetal analgesia was administered. RESULTS: We retrieved 34 papers. In three
      papers, the procedure did not hurt the fetus, being performed on fetal annexes,
      in two papers, it was performed in the first half of pregnancy, when pain
      perception is unlikely. In 10 of the 29 remaining papers, fetal surgery was
      performed using direct fetal analgesia, while in 19, analgesia was administered
      only to the mother. In most cases, fetal direct analgesia was obtained using i.m.
      opioids, and muscle relaxant. Rare drawbacks on either fetuses or mothers due to
      fetal analgesia were reported. CONCLUSION: Fetal direct analgesia is performed
      only in a minority of cases and no study gives details about fetal reactions to
      pain. More research is needed to assess or exclude its possible long-term
      drawbacks, as well as the actual consequences of pain during surgery.

PMID- 22881839
TI  - Solution additives that desalt protein ions in native mass spectrometry.
AB  - The presence of many salts, such as sodium chloride, can adversely affect the
      performance of native electrospray ionization mass spectrometry for the analysis
      of proteins and protein complexes by reducing the overall molecular ion
      abundances and distributing signal for any given charge state into many
      cationized forms with various numbers of adducts attached. Several solution
      additives, such as ammonium bromide, ammonium iodide, and NaSbF(6), can
      significantly lower the extent of sodium ion adduction to the molecular ions of
      proteins and protein complexes. For ubiquitin, addition of 25 mM ammonium bromide
      or ammonium iodide into aqueous solutions also containing 1.0 mM NaCl results in
      a factor of 72 and 56 increase, respectively, in the relative abundances of the
      fully protonated molecular ions compared to when these additives are not present.
      The effectiveness of this method for reducing sodium ion adduction is related to
      the low proton affinity (PA) values of the anions. Anions with very low PA also
      have a propensity to adduct as an acid molecule, but these adducts can be readily
      dissociated from the molecular ions either by activation in the source or
      subsequently by collisional activation in the mass spectrometer. This method of
      reducing sodium ion adduction to proteins is simple and requires no experimental
      modifications, making it an attractive alternative to other methods for desalting
      proteins prior to mass spectrometry analysis.

PMID- 22881841
TI  - Enhanced electrogenerated chemiluminescence of phenylethynylpyrene derivatives:
      use of weakly electron-donating group as a substituent.
AB  - A weakly donating group (n-propyl) has been used as a substituent at the para
      position of the phenyl group for a series of phenylethynylpyrene derivatives
      where the number of phenylethynyl peripheral arms appended to the pyrene core is
      varied. This system markedly improved the concurrent stability of both cation and
      anion radicals and consequently greatly improved electrogenerated
      chemiluminescence (ECL). Density functional theory (DFT)-based theoretical
      calculations supported the associated photophysical and electrochemical
      properties of the series compounds.

PMID- 22881842
TI  - Can medical repatriation be ethical? Establishing best practices.
AB  - Hospitals in the United States have been engaging in the practice of returning
      immigrant patients, usually undocumented immigrant patients, to their country of
      origin when the patient has long-term medical needs for which no reimbursement is
      available. I argue that for such an action to be ethical, it must be done in
      accordance with the mission and values of hospitals. I describe three standards
      that an individual instance of repatriation must meet to be ethical: (1) patient
      best interests, (2) medical due diligence, and (3) informed consent. I argue that
      these should form the basis for best practices in regard to medical repatriation
      for all hospitals in the United States.

PMID- 22881843
TI  - Patient autonomy and the unfortunate choice between repatriation and suboptimal
      treatment.

PMID- 22881844
TI  - Medical repatriation: the need for a bigger picture.

PMID- 22881845
TI  - Medical repatriation does not justify hospital entanglement in nonmedical
      matters.

PMID- 22881846
TI  - Migration and health: discovering new territory for bioethics.

PMID- 22881847
TI  - Criteria for medical repatriation and the context of inadequate access to care.

PMID- 22881848
TI  - Reframing the ethical issues in part-human animal research: the unbearable
      ontology of inexorable moral confusion.
AB  - Research that involves the creation of animals with human-derived parts opens the
      door to potentially valuable scientific and therapeutic advances, yet invokes
      unsettling moral questions. Critics and champions alike stand to gain from clear
      identification and careful consideration of the strongest ethical objections to
      this research. A prevailing objection argues that crossing the human/nonhuman
      species boundary introduces inexorable moral confusion (IMC) that warrants a
      restriction to this research on precautionary grounds. Though this objection may
      capture the intuitions of many who find this research unsettling, it relies on
      mistaken views of both biology and moral standing, ultimately distorting the
      morally relevant facts. We critically examine IMC, identify mistaken essentialist
      assumptions, and reframe ethical concerns. The upshot is a stronger line of
      objection that encourages a more inclusive and productive ethical discourse.

PMID- 22881849
TI  - Part-human animal research: the imperative to move beyond a philosophical debate.

PMID- 22881850
TI  - Who are my parents? Why assigning moral categories to genealogical relations
      leads to more confusion.

PMID- 22881851
TI  - Uncanny animals: thinking differently about ethics and the animal-human
      relationship.

PMID- 22881852
TI  - Ontological kinds versus biological species.

PMID- 22881853
TI  - The two-essence problem that wasn't.

PMID- 22881854
TI  - Telecare, surveillance, and the welfare state.
AB  - In Europe, telecare is the use of remote monitoring technology to enable
      vulnerable people to live independently in their own homes. The technology
      includes electronic tags and sensors that transmit information about the user's
      location and patterns of behavior in the user's home to an external hub, where it
      can trigger an intervention in an emergency. Telecare users in the United Kingdom
      sometimes report their unease about being monitored by a "Big Brother," and the
      same kind of electronic tags that alert telecare hubs to the movements of someone
      with dementia who is "wandering" are worn by terrorist suspects who have been
      placed under house arrest. For these and other reasons, such as ordinary privacy
      concerns, telecare is sometimes regarded as an objectionable extension of a
      "surveillance state." In this article, we defend the use of telecare against the
      charge that it is Orwellian. In the United States, the conception of telecare
      primarily as telemedicine, and the fact that it is not typically a government
      responsibility, make a supposed connection with a surveillance state even more
      doubtful than in Europe. The main objection, we argue, to telecare is not its
      intrusiveness, but the danger of its deepening the isolation of those who use it.
      There are ways of organizing telecare so that the independence and privacy of
      users are enhanced, but personal isolation may be harder to address. As telecare
      is a means of reducing the cost of publicly provided social and health care, and
      the need to reduce public spending is growing, the correlative problem of
      isolation must be addressed alongside the goal of promoting independence.

PMID- 22881855
TI  - Malicious meddling or transparent tracking? Telecare as a logical extension of
      modern communications technology.

PMID- 22881856
TI  - Personal health monitoring and human interaction.

PMID- 22881857
TI  - These are the "little brothers" we should be worried about.

PMID- 22881858
TI  - Taking patient privacy and autonomy more seriously: why an Orwellian account is
      not sufficient.

PMID- 22881859
TI  - Self-perception and self-determination in surveillance conditions.

PMID- 22881860
TI  - What autonomy for telecare? An externalist approach.

PMID- 22881861
TI  - Using foucault to recast the telecare debate.

PMID- 22881863
TI  - Response to open peer commentaries on "can medical repatriation be ethical?
      Establishing best practices".

PMID- 22881864
TI  - Communicating with clinicians: the experiences of surrogate decision-makers for
      hospitalized older adults.
AB  - OBJECTIVES: To describe communication experiences of surrogates who had recently
      made a major medical decision for a hospitalized older adult. DESIGN:
      Semistructured interviews about a recent hospitalization. SETTING: Two hospitals
      affiliated with one large medical school: an urban public hospital and a
      university-affiliated tertiary referral hospital. PARTICIPANTS: Surrogates were
      eligible if they had recently made a major medical decision for a hospitalized
      individual aged 65 and older and were available for an interview within 1 month
      (2-5 months if the patient died). MEASUREMENTS: Interviews were audio-recorded,
      transcribed, and analyzed using methods of grounded theory. RESULTS: Thirty-five
      surrogates were interviewed (80% female, 44% white, 56% African American). Three
      primary themes emerged. First, it was found that the nature of surrogate
      clinician relationships was best characterized as a relationship with a "team" of
      clinicians rather than individual clinicians because of frequent staff changes
      and multiple clinicians. Second, surrogates reported their communication needs,
      including frequent communication, information, and emotional support. Surrogates
      valued communication from any member of the clinical team, including nurses,
      social workers, and physicians. Third, surrogates described trust and mistrust,
      which were formed largely through surrogates' communication experiences.
      CONCLUSION: In the hospital, surrogates form relationships with a "team" of
      clinicians rather than with individuals, yet effective communication and
      expressions of emotional support frequently occur, which surrogates value highly.
      Future interventions should focus on meeting surrogates' needs for frequent
      communication and high levels of information and emotional support.

PMID- 22881865
TI  - Metallofullerene-nanoplatform-delivered interstitial brachytherapy improved
      survival in a murine model of glioblastoma multiforme.
AB  - Fullerenes are used across scientific disciplines because of their diverse
      properties gained by altering encapsulated or surface-bound components. In this
      study, the recently developed theranostic agent based on a radiolabeled
      functionalized metallofullerene ((177)Lu-DOTA-f-Gd(3)N@C(80)) was synthesized
      with high radiochemical yield and purity. The efficacy of this agent was
      demonstrated in two orthotopic xenograft brain tumor models of glioblastoma
      multiforme (GBM). A dose-dependent improvement in survival was also shown. The in
      vivo stability of the agent was verified through dual label measurements of
      biological elimination from the tumor. Overall, these results provide evidence
      that nanomaterial platforms can be used to deliver effective interstitial
      brachytherapy.

PMID- 22881867
TI  - Puerperal uterine inversion in the Netherlands: a nationwide cohort study.
AB  - Puerperal uterine inversion is a severe but rare obstetric complication of yet
      unknown origin. In this two-year study we determine the incidence of this
      complication and we describe associated risk factors to expose its etiology. All
      cases of uterine inversion were included from a nationwide cohort study which
      contained all 98 hospitals with a maternity unit in the Netherlands. We reviewed
      the medical records of 15 patients, resulting an incidence of approximately 1 in
      20 000 vaginal births. Fourteen cases (93.3%) were classified as low-risk
      pregnancies at booking. Nulliparous women were not overrepresented and the main
      associated factors were signs of prolonged labor followed by third stage
      manipulation. This study is the first population-based study for uterine
      inversion. With the reported associated factors and occurrence in women with a
      low-risk profile, we show that every birth attendant should be able to detect
      this rare but severe complication.

PMID- 22881866
TI  - Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by
      virtual screening of a fragment library.
AB  - Human aldo-keto reductases 1C1-1C4 (AKR1C1-AKR1C4) function in vivo as 3-keto-,
      17-keto-, and 20-ketosteroid reductases and regulate the activity of androgens,
      estrogens, and progesterone and the occupancy and transactivation of their
      corresponding receptors. Aberrant expression and action of AKR1C enzymes can lead
      to different pathophysiological conditions. AKR1C enzymes thus represent
      important targets for development of new drugs. We performed a virtual high
      throughput screen of a fragment library that was followed by biochemical
      evaluation on AKR1C1-AKR1C4 enzymes. Twenty-four structurally diverse compounds
      were discovered with low MUM K(i) values for AKR1C1, AKR1C3, or both. Two
      structural series included the salicylates and the N-phenylanthranilic acids, and
      additionally a series of inhibitors with completely novel scaffolds was
      discovered. Two of the best selective AKR1C3 inhibitors had K(i) values of 0.1
      and 2.7 MUM, exceeding expected activity for fragments. The compounds identified
      represent an excellent starting point for further hit-to-lead development.

PMID- 22881868
TI  - Prediction for relapse and prognosis of newly diagnosed epilepsy.
AB  - OBJECTIVE: The objective of this study was to investigate the timing of therapy
      initiation and other clinical factors as potential predictors for relapse and
      prognosis of epilepsy, based on hospital-based prospective observational data in
      China. METHODS: One hundred and seventy-one newly diagnosed patients with one or
      more seizures were recruited and followed for at least 2 years. Kaplan-Meier
      survival analysis was used for calculating recurrence and remission rates.
      Univariate and multivariate analyses for risk factors were performed using Cox
      proportional hazards model. RESULTS: Among the 171 patients analyzed, more
      patients had partial (54.4%) than generalized seizures (45.6%). The range of
      patients' age was 6-70 years, but 70% were under 16 years of age. Multiple
      seizure types (HR = 2.01; 95% CI, 1.31-3.10), epileptiform electroencephalogram
      (EEG) abnormality (HR = 1.95; 95% CI, 1.09-3.49), and >1 seizure monthly before
      treatment (HR = 2.74; 95% CI, 1.69-4.51) were predictors of seizure recurrence.
      The best negative predictors of remission were as follows: relapse (HR = 0.13;
      95% CI, 0.07-0.23) and epileptiform EEG within 1 year of treatment (HR = 0.61;
      95% CI, 0.39-0.97). Delayed treatment after three or more seizures did not
      significantly increase the risk of recurrence (P = 0.70) or remission (P = 0.31)
      compared with early treatment after one or two seizures. CONCLUSIONS: Multiple
      seizure types, epileptiform EEG abnormality, and >1 seizure monthly before
      treatment predict seizure recurrence. Relapse and epileptiform EEG within 1 year
      of treatment predict adverse seizure outcome. Early treatment does not affect
      relapse or prognosis.

PMID- 22881869
TI  - Redox reactions and microbial killing in the neutrophil phagosome.
AB  - SIGNIFICANCE: When neutrophils kill microorganisms, they ingest them into
      phagosomes and bombard them with a burst of reactive oxygen species. RECENT
      ADVANCES: This review focuses on what oxidants are produced and how they kill.
      The neutrophil NADPH oxidase is activated and shuttles electrons from NADPH in
      the cytoplasm to oxygen in the phagosomal lumen. Superoxide is generated in the
      narrow space between the ingested organism and the phagosomal membrane and
      kinetic modeling indicates that it reaches a concentration of around 20 MUM.
      Degranulation leads to a very high protein concentration with up to millimolar
      myeloperoxidase (MPO). MPO has many substrates, but its main phagosomal reactions
      should be to dismutate superoxide and, provided adequate chloride, catalyze
      efficient conversion of hydrogen peroxide to hypochlorous acid (HOCl). Studies
      with specific probes have shown that HOCl is produced in the phagosome and reacts
      with ingested bacteria. The amount generated should be high enough to kill.
      However, much of the HOCl reacts with phagosomal proteins. Generation of
      chloramines may contribute to killing, but the full consequences of this are not
      yet clear. CRITICAL ISSUES: Isolated neutrophils kill most of the ingested
      microorganisms rapidly by an MPO-dependent mechanism that is almost certainly due
      to HOCl. However, individuals with MPO deficiency rarely have problems with
      infection. A possible explanation is that HOCl provides a frontline response that
      kills most of the microorganisms, with survivors killed by nonoxidative
      processes. The latter may deal adequately with low-level infection but with high
      exposure, more efficient HOCl-dependent killing is required. FUTURE DIRECTIONS:
      Better quantification of HOCl and other oxidants in the phagosome should clarify
      their roles in antimicrobial action.

PMID- 22881870
TI  - epv, Encoding a hypothetical protein, is regulated by DSF-mediating quorum
      sensing as well as global regulator Clp and is required for optimal virulence in
      Xanthomonas oryzae pv. oryzicola.
AB  - Xanthomonas oryzae pv. oryzicola causes bacterial leaf streak in rice, a
      destructive disease worldwide. In this study, six putative hypothetical secreted
      proteins, which were absent in X. oryzae pv. oryzae, were detected from X. oryzae
      pv. oryzicola strain BLS256. Disruption-based mutagenesis study revealed that one
      of them, Xoc_15235, named as extracellular polysaccharide and virulence-related
      gene (epv), was required for the optimal virulence in host rice but not for the
      induction of a hypersensitive reaction in nonhost tobacco. Sequence analysis
      revealed that epv was highly conserved in Xanthomonas spp. (except X. oryzae pv.
      oryzae). In-frame deletion of epv in X. oryzae pv. oryzicola dramatically
      impaired pathogen virulence and extracellular polysaccharide (EPS) production,
      one of the important known virulence-associated functions in Xanthomonas spp.
      Quantitative real-time reverse-transcription polymerase chain reaction showed
      that expression of both gumB (a gene encoding exopolysaccharide xanthan
      biosynthesis export protein) and a known virulence-related gene, pgk (encoding
      phosphoglycerate kinase), were obviously reduced in the epv-deletion mutant
      compared with the wild-type strain Rs105. In addition, we observed that epv was
      positively regulated by both diffusible signal factor and global regulator Clp in
      X. oryzae pv. oryzicola. Taken together, the novel roles and genetics of epv of
      X. oryzae pv. oryzicola in the EPS production and virulence were investigated for
      the first time.

PMID- 22881871
TI  - Effects of sunlight exposure on grapevine powdery mildew development.
AB  - Natural and artificially induced shade increased grapevine powdery mildew
      (Erysiphe necator) severity in the vineyard, with foliar disease severity 49 to
      75% higher relative to leaves in full sun, depending on the level of natural
      shading experienced and the individual experiment. Cluster disease severities
      increased by 20 to 40% relative to those on check vines when ultraviolet (UV)
      radiation was filtered from sunlight reaching vines in artificial shading
      experiments. Surface temperatures of leaves in full sunlight averaged 5 to 8
      degrees C higher than those in natural shade, and in one experiment, filtering
      80% of all wavelengths of solar radiation, including longer wavelengths
      responsible for heating irradiated tissues, increased disease more than filtering
      UV alone. In controlled environment experiments, UV-B radiation reduced
      germination of E. necator conidia and inhibited both colony establishment (hyphal
      formation and elongation) and maturity (latent period). Inhibitory effects of UV
      B radiation were significantly greater at 30 degrees C than at 20 or 25 degrees
      C. Thus, sunlight appears to inhibit powdery mildew development through at least
      two mechanisms, i.e., (i) UV radiation's damaging effects on exposed conidia and
      thalli of the pathogen; and (ii) elevating temperatures of irradiated tissues to
      a level supraoptimal or inhibitory for pathogen development. Furthermore, these
      effects are synergistic at temperatures near the upper threshold for disease
      development.

PMID- 22881872
TI  - Development of a loop-mediated isothermal amplification procedure as a sensitive
      and rapid method for detection of 'candidatus Liberibacter solanacearum' in
      potatoes and Psyllids.
AB  - This study reports the development of a loop-mediated isothermal amplification
      procedure (LAMP) for polymerase chain reaction (PCR)-based detection of
      'Candidatus Liberibacter solanacearum', the bacterial causal agent of potato
      zebra chip (ZC) disease. The 16S rDNA gene of 'Ca. Liberibacter solanacearum' was
      used to design a set of six primers for LAMP PCR detection of the bacterial
      pathogen in potato plants and the psyllid vector. The advantage of the LAMP
      method is that it does not require a thermocycler for amplification or agarose
      gel electrophoresis for resolution. Positive LAMP results can be visualized
      directly as a precipitate. The LAMP strategy reported here reliably detected 'Ca.
      Liberibacter solanacearum' and the closely related species 'Ca. Liberibacter
      asiaticus', the causative agent of huanglongbing disease of citrus, in plant DNA
      extracts. Although not as sensitive as quantitative real-time PCR, LAMP detection
      was equivalent to conventional PCR in tests of ZC-infected potato plants from the
      field. Thus, the LAMP method shows strong promise as a reliable, rapid, and cost
      effective method of detecting 'Ca. Liberibacter' pathogens in psyllids and field
      grown potato plants and tubers.

PMID- 22881986
TI  - Carbon and nitrogen isotopic signatures and nitrogen profile to identify
      adulteration in organic fertilizers.
AB  - Recently it has been shown that stable isotopes of nitrogen can be used to
      discriminate between organic and synthetic fertilizers, but the robustness of the
      approach is questionable. This work developed a comprehensive method that is far
      more robust in identifying an adulteration of organic nitrogen fertilizers.
      Organic fertilizers of various types (manures, composts, blood meal, bone meal,
      fish meal, products of poultry and plant productions, molasses and seaweed based,
      and others) available on the North American market were analyzed to reveal the
      most sensitive criteria as well as their quantitative ranges, which can be used
      in their authentication. Organic nitrogen fertilizers of known origins with a
      wide delta(15)N range between -0.55 and 28.850/00 (n = 1258) were characterized
      for C and N content, delta(13)C, delta(15)N, viscosity, pH, and nitrogen profile
      (urea, ammonia, organic N, water insoluble N, and NO3). A statistically
      significant data set of characterized unique organic nitrogen fertilizers (n =
      335) of various known origins has been assembled. Deliberately adulterated
      samples of different types of organic fertilizers mixed with synthetic
      fertilizers at a wide range of proportions have been used to develop the
      quantitative critical characteristics of organic fertilizers as the key
      indicators of their adulteration. Statistical analysis based on the discriminant
      functions of the quantitative critical characteristics of organic nitrogen
      fertilizers from 14 different source materials revealed a very high average rate
      of correct classification. The developed methodology has been successfully used
      as a source identification tool for numerous commercial nitrogen fertilizers
      available on the North American market. 

PMID- 22881873
TI  - Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes.
AB  - This study investigated the in vivo pulmonary toxicity of inhaled multi-walled
      carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m3, 5 h/day) for
      2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration.
      MWCNT-induced pulmonary inflammation was assessed by determining whole lung
      lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed
      by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as
      a marker of alveolar air-blood barrier integrity. These parameters significantly
      increased in MWCNT-exposed mice versus controls and were dose-dependent.
      Histopathologic alterations identified in the lung included (1) bronciolocentric
      inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3)
      fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT
      translocated to the lymph node where the deep paracortex was expanded after 8 or
      12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation
      and damage with rapid development of pulmonary fibrosis, and also demonstrated
      that MWCNT can reach the pleura after inhalation exposure.

PMID- 22881987
TI  - (Photo)chlorination-induced physicochemical transformation of aqueous fullerene
      nC60.
AB  - This study confirmed the physicochemical transformation of aqueous fullerene
      aggregates (nC(60)) produced via solvent exchange from toluene by chlorine in the
      dark and under fluorescent light (representing visible light) by comparing the
      changes in light absorbance at 700 nm and size distribution of nC(60) and
      characterizing the photochlorination products of nC(60) by XPS, FTIR and TOF-SIMS
      techniques. The (photo)chlorination of nC(60) was enhanced by increasing the
      chlorine dosage and the salinity concentration, and the presence of fluorescent
      light. During (photo)chlorination, nC(60) underwent surface chlorination,
      hydroxylation and oxidation, and was transformed into products containing carbon
      chlorine, epoxy and hydroxyl functional groups. Extensive (photo)chlorination
      produced products that might not possess the isolated benzenoid ring structure on
      their cages, although they retained the 60-carbon cage structure. These findings
      imply the necessity of assessing the fate and toxicity of nC(60) after
      (photo)chlorination in both engineered and natural environments and demonstrate a
      simple way to produce new nC(60) derivatives that contain chlorine and oxygen.

PMID- 22881988
TI  - Poor oral health as an obstacle to employment for Medicaid beneficiaries with
      disabilities.
AB  - OBJECTIVES: To inform policy with better information about the oral health-care
      needs of a Medicaid population that engages in employment, that is, people ages
      16 to 64 with Social Security-determined disabilities enrolled in a Medicaid Buy
      In program. METHODS: Statistically test for significant differences among
      responses to a Medicaid Buy-In program satisfaction survey that included oral
      health questions from the Centers for Disease Control and Prevention's Behavioral
      Risk Factor Surveillance System and the Oral Health Impact Profile (OHIP) to
      results for the state's general population and the US general population.
      RESULTS: All measures of dental care access and oral health were significantly
      worse for the study population as compared with a state general population or a
      US general population. Differences were particularly pronounced for the OHIP
      measure for difficulty doing one's job due to dental problems, which was almost
      five times higher for the study population. CONCLUSIONS: More comprehensive
      dental benefits for the study population could result in increased oral and
      overall health, and eventual cost savings to Medicaid as more people work, have
      improved health, and pay premiums for coverage.

PMID- 22881989
TI  - Spindle-like mesoporous alpha-Fe2O3 anode material prepared from MOF template for
      high-rate lithium batteries.
AB  - Spindle-like porous alpha-Fe(2)O(3) was prepared from an iron-based metal organic
      framework (MOF) template. When tested as anode material for lithium batteries
      (LBs), this spindle-like porous alpha-Fe(2)O(3) shows greatly enhanced
      performance of Li storage. The particle with a length and width of ~0.8 and ~0.4
      MUm, respectively, was composed of clustered Fe(2)O(3) nanoparticles with sizes
      of <20 nm. The capacity of the porous alpha-Fe(2)O(3) retained 911 mAh g(-1)
      after 50 cycles at a rate of 0.2 C. Even when cycled at 10 C, comparable capacity
      of 424 mAh g(-1) could be achieved.

PMID- 22881990
TI  - Predictors of psychiatric and seizure outcome following temporal lobe epilepsy
      surgery.
AB  - PURPOSE: Neurosurgery is an effective therapy for selected individuals with
      medically refractory temporal lobe epilepsy (TLE). De novo psychopathology may
      complicate the postsurgical outcome. Our aims were to identify predictors of de
      novo psychiatric and seizure outcome following TLE surgery. METHODS: Medical
      records of 280 patients who underwent TLE surgery were reviewed. Preoperative and
      postoperative psychiatric diagnoses were identified, in addition to information
      on seizure recurrence and neuropsychological status. Logistic regression analysis
      was used to identify predictors of having a de novo psychiatric diagnosis and
      remaining seizure-free within 4 years following surgery. KEY FINDINGS: One
      hundred five patients (38%) had significant psychiatric problems within 4 years
      following TLE surgery. Fifty-one patients (18%) developed de novo
      psychopathology; half of cases presented within 6 months and 90% of
      psychopathologies persisted 6 months or longer. A preoperative history of
      secondary generalized tonic-clonic seizure(s) (SGTCS) was an independent
      predictor of de novo psychopathology (odds ratio [OR] 2.73, 95% confidence
      interval [CI] 1.14-6.59, p = 0.02). From patients with available seizure data,
      49% (127 of 258) remained seizure-free for 4 years after surgery. Patients with a
      history of SGTCS (OR 0.47, 95% CI 0.25-0.90, p = 0.02) and those with a
      preoperative psychiatric diagnosis (OR 0.53, 95% CI 0.28-0.98, p = 0.04) were
      significantly less likely to remain seizure-free. SIGNIFICANCE: De novo
      psychopathology is a significant complication of TLE surgery. Inclusion of
      neuropsychiatric assessments in the presurgical evaluation may lead to increase
      in the power of prognostic models used to predict the neurologic outcome of TLE
      surgery.

PMID- 22881991
TI  - Teaching emotion recognition skills to young children with autism: a randomised
      controlled trial of an emotion training programme.
AB  - BACKGROUND: Children with autism have difficulties in emotion recognition and a
      number of interventions have been designed to target these problems. However, few
      emotion training interventions have been trialled with young children with autism
      and co-morbid ID. This study aimed to evaluate the efficacy of an emotion
      training programme for a group of young children with autism with a range of
      intellectual ability. METHODS: Participants were 55 children with autistic
      disorder, aged 4-7 years (FSIQ 42-107). Children were randomly assigned to an
      intervention (n = 28) or control group (n = 27). Participants in the intervention
      group watched a DVD designed to teach emotion recognition skills to children with
      autism (the Transporters), whereas the control group watched a DVD of Thomas the
      Tank Engine. Participants were assessed on their ability to complete basic
      emotion recognition tasks, mindreading and theory of mind (TOM) tasks before and
      after the 4-week intervention period, and at 3-month follow-up. RESULTS: Analyses
      controlled for the effect of chronological age, verbal intelligence, gender and
      DVD viewing time on outcomes. Children in the intervention group showed improved
      performance in the recognition of anger compared with the control group, with few
      improvements maintained at 3-month follow-up. There was no generalisation of
      skills to TOM or social skills. CONCLUSIONS: The Transporters programme showed
      limited efficacy in teaching basic emotion recognition skills to young children
      with autism with a lower range of cognitive ability. Improvements were limited to
      the recognition of expressions of anger, with poor maintenance of these skills at
      follow-up. These findings provide limited support for the efficacy of the
      Transporters programme for young children with autism of a lower cognitive range.

PMID- 22881992
TI  - Low dose hydroxyurea is effective in reducing the incidence of painful crisis and
      frequency of blood transfusion in sickle cell anemia patients from eastern India.
AB  - There are several questions pertaining to dosage, duration and potential long
      term toxicity of hydroxyurea (HU) therapy. Use of HU is extremely limited in
      eastern India because of its high cost and apprehension of its toxicities. We
      undertook this study to assess the clinical, biochemical and hematological
      efficacy of minimal dose HU (10 mg/kg/day) in 118 sickle cell anemia patients (27
      pediatric and 91 adults). The frequency of painful crises reduced significantly
      in 71.5 and 92.2% in pediatric and adult cases, respectively. Ninety-five percent
      of the patients became transfusion independent. The baseline Hb F, total
      hemoglobin (Hb), MCV, MCH and MCHC levels increased significantly, whereas the
      WBC, platelet count and total serum bilirubin values decreased significantly.
      This is the first study of minimal dose HU therapy in eastern India that showed
      impressive improvement in clinical and hematological parameters with minimal
      toxicity.

PMID- 22881994
TI  - Changes in charge distribution, molecular volume, accessible surface area and
      electronic structure along the reaction coordinate for a carbocationic triple
      shift rearrangement of relevance to diterpene biosynthesis.
AB  - The nature of the recently described "triple shift" rearrangement of a
      biologically relevant carbocation (computed in the absence of a surrounding
      enzyme) is characterized by examining the evolution of charge distribution,
      molecular volume, accessible surface area, and multicenter bonding indices along
      its reaction coordinate. Implications for interaction of the rearranging
      carbocation with a terpene synthase active site are discussed.

PMID- 22881993
TI  - Selective inhibition by simvastatin of IRF3 phosphorylation and TSLP production
      in dsRNA-challenged bronchial epithelial cells from COPD donors.
AB  - BACKGROUND AND PURPOSE: Statin treatment may ameliorate viral infection-induced
      exacerbations of chronic obstructive pulmonary disease (COPD), which exhibit Th2
      type bronchial inflammation. Thymic stromal lymphopoietin (TSLP), a hub cytokine
      switching on Th2 inflammation, is overproduced in viral and dsRNA-stimulated
      bronchial epithelial cells from COPD donors. Hence, TSLP may be causally involved
      in exacerbations. This study tests the hypothesis that simvastatin inhibits dsRNA
      induced TSLP. EXPERIMENTAL APPROACH: Epithelial cells, obtained by bronchoscopy
      from COPD (n = 7) and smoker control (n = 8) donors, were grown and stimulated
      with a viral infection and danger signal surrogate, dsRNA (10 MUg.mL(-1) ). Cells
      were treated with simvastatin (0.2-5 MUg.mL(-1) ), with or without mevalonate (13
      26 MUg.mL(-1) ), or dexamethasone (1 MUg.mL(-1) ) before dsRNA. Cytokine
      expression and production, and transcription factor (IRF3 and NF-kappaB)
      activation were determined. KEY RESULTS: dsRNA induced TSLP, TNF-alpha, CXCL8 and
      IFN-beta. TSLP was overproduced in dsRNA-exposed COPD cells compared with
      control. Simvastatin, but not dexamethasone, concentration-dependently inhibited
      dsRNA-induced TSLP. Unexpectedly, simvastatin acted independently of mevalonate
      and did not affect dsRNA-induced NF-kappaB activation nor did it reduce
      production of TNF-alpha and CXCL8. Instead, simvastatin inhibited dsRNA-induced
      IRF3 phosphorylation and generation of IFN-beta. CONCLUSIONS AND IMPLICATIONS:
      Independent of mevalonate and NF-kappaB, previously acknowledged anti
      inflammatory mechanisms of pleiotropic statins, simvastatin selectively inhibited
      dsRNA-induced IRF3 activation and production of TSLP and IFN-beta in COPD
      epithelium. These data provide novel insight into epithelial generation of TSLP
      and suggest paths to be exploited in drug discovery aimed at inhibiting TSLP
      induced pulmonary immunopathology.

PMID- 22881995
TI  - How to read fetal heart rate tracings in labor: a comparison between ACOG and
      NICE guidelines.
AB  - The aim of this study was to assess reproducibility and clinical relevance of
      current guidelines on fetal heart rate interpretation in labor. Two obstetricians
      with comparable experience analyzed one hundred fetal heart rate tracings. One
      doctor made a first analysis using American College of Obstetricians and
      Gynecologists (ACOG) 2009 guideline's criteria; the other used National Institute
      for Health and Clinical Excellence (NICE) 2007 guideline's criteria; subsequently
      they repeated the evaluation crossing the guidelines used. The primary outcome of
      this experiment was to determine the time spent to evaluate the tracings,
      secondary outcomes were: the intraobserver concordance (concordance of the
      evaluation with the two systems for each investigator), the interobserver
      concordance (concordance between the interpretation given by each investigator)
      and. the concordance between operators' grading and actual outcome of labor. The
      interpretation of fetal heart rate tracings was longer using ACOG criteria. The
      intraobserver agreement was significant. The interobserver agreement was better
      using NICE guidelines. The same trend showed for the concordance between
      investigators' grading and actual outcomes There was more discordance in worse
      outcomes. Both guidelines are interesting and useful, but NICE seems easier to
      handle than ACOG.

PMID- 22881997
TI  - Highly efficient assay of circulating tumor cells by selective sedimentation with
      a density gradient medium and microfiltration from whole blood.
AB  - Isolation of circulating tumor cells (CTCs) by size exclusion can yield poor
      purity and low recovery rates, due to large variations in size of CTCs, which may
      overlap with leukocytes and render size-based filtration methods unreliable. This
      report presents a very sensitive, selective, fast, and novel method for isolation
      and detection of CTCs. Our assay platform consists of three steps: (i) capturing
      CTCs with anti-EpCAM conjugated microbeads, (ii) removal of unwanted hematologic
      cells (e.g., leukocytes, erythrocytes, etc.) by selective sedimentation of CTCs
      within a density gradient medium, and (iii) simple microfiltration to collect
      these cells. To demonstrate the efficacy of this assay, MCF-7 breast cancer cells
      (average diameter, 24 MUm) and DMS-79 small cell lung cancer cells (average
      diameter, 10 MUm) were used to model CTCs. We investigated the relative
      sedimentation rates for various cells and/or particles, such as CTCs conjugated
      with different types of microbeads, leukocytes, and erythrocytes, in order to
      maximize differences in the physical properties. We observed that greater than
      99% of leukocytes in whole blood were effectively removed at an optimal
      centrifugal force, due to differences in their sedimentation rates, yielding a
      much purer sample compared to other filter-based methods. We also investigated
      not only the effect of filtration conditions on recovery rates and sample purity
      but also the sensitivity of our assay platform. Our results showed a near perfect
      recovery rate (~99%) for MCF-7 cells and very high recovery rate (~89%) for DMS
      79 cells, with minimal amounts of leukocytes present.

PMID- 22881998
TI  - Peptide-microgel interactions in the strong coupling regime.
AB  - The interaction between lightly cross-linked poly(acrylic acid) microgels and
      oppositely charged peptides was investigated as a function of peptide length,
      charge density, pH, and salt concentration, with emphasis on the strong coupling
      regime at high charge contrast. By micromanipulator-assisted light microscopy,
      the equilibrium volume response of single microgel particles upon oligolysine and
      oligo(lysine/alanine) absorption could be monitored in a controlled fashion.
      Results show that microgel deswelling, caused by peptide binding and network
      neutralization, increases with peptide length (3 < 5 < 10) and charge density
      (30% < 50% < 100%). Furthermore, oligomer-induced microgel deswelling was more
      pronounced at pH 5 than at pH 8, reflecting the lower network charge density in
      the former case (pK(a) for the isolated acrylic acid ~4.7). In order to describe
      these highly coupled systems, a model was developed, in which counterion/peptide
      mediated electrostatic attraction between the network chains is described using
      an exponential force law, and the network elasticity by the inverse Langevin
      theory. The model was used to calculate the composition of microgels in contact
      with reservoir solutions of peptides and simple electrolytes. At high
      electrostatic coupling, the calculated swelling curves were found to display
      first-order phase transition behavior. The model was demonstrated to capture pH-
      and electrolyte-dependent microgel swelling, as well as effects of peptide length
      and charge density on microgel deswelling. The analysis demonstrated that the
      peptide charge (length), rather than the peptide charge density, determines
      microgel deswelling. Furthermore, a transition between continuous and discrete
      network collapse was identified, consistent with experimental results in the
      present investigations, as well as with results from the literature on microgel
      deswelling caused by multivalent cations.

PMID- 22881999
TI  - Improved methodology for the preparation of water-soluble maleimide
      functionalized small gold nanoparticles.
AB  - Improved methodology to prepare maleimide-functionalized, water-soluble, small
      (<3 nm) gold nanoparticles using a retro-Diels-Alder strategy that we developed
      for similar organic-soluble AuNP's is described. Importantly, our results suggest
      that a recent paper by Zhu, Waengler, Lennox, and Schirrmacher describing a
      similar strategy gave results inconsistent with the formation of the titled
      maleimide-modified AuNP (Zhu, J.; Waengler, C.; Lennox, R. B.; Schirrmacher, R.
      Langmuir2012, 28, 5508) as the major product, but consistent with the major
      product being an adduct derived from the hydrolysis of maleimide formed under the
      conditions used for the required deprotection of the maleimide. Our methodology
      provides an efficient and accessible route to pure maleimide-modified small
      AuNP's that circumvents the formation of the hydrolysis product. The maleimide
      modified small AuNP's are versatile because they are soluble in water and in a
      wide range of organic solvents and their reactivity can now be properly exploited
      as a reactive moiety in Michael addition for bioconjugation studies in aqueous
      solution.

PMID- 22882000
TI  - Prevalence of cognitive impairment in older adults with heart failure.
AB  - OBJECTIVES: To determine the prevalence of cognitive impairment in older adults
      with heart failure (HF). DESIGN: Cross-sectional analysis of the 2004 wave of the
      nationally representative Health and Retirement Study linked to 2002 to 2004
      Medicare administrative claims. SETTING: United States, community. PARTICIPANTS:
      Six thousand one hundred eighty-nine individuals aged 67 and older. MEASUREMENTS:
      An algorithm was developed using a combination of self- and proxy report of a
      heart problem and the presence of one or more Medicare claims in administrative
      files using standard HF diagnostic codes. On the basis of the algorithm, three
      categories were created to characterize the likelihood of a HF diagnosis: high or
      moderate probability of HF, low probability of HF, and no HF. Cognitive function
      was assessed using a screening measure of cognitive function or according to
      proxy rating. Age-adjusted prevalence estimates of cognitive impairment were
      calculated for the three groups. RESULTS: The prevalence of cognitive impairment
      consistent with dementia in older adults with HF was 15%, and the prevalence of
      mild cognitive impairment was 24%. The odds of dementia in those with HF were
      significantly higher, even after adjustment for age, education level, net worth,
      and prior stroke (odds ratio = 1.52, 95% confidence interval = 1.14-2.02).
      CONCLUSION: Cognitive impairment is common in older adults with HF and is
      independently associated with risk of dementia. A cognitive assessment should be
      routinely incorporated into HF-focused models of care.

PMID- 22882002
TI  - Generation and evaluation of bispecific affibody molecules for simultaneous
      targeting of EGFR and HER2.
AB  - Coexpression of several ErbB receptors has been found in many cancers and has
      been linked with increased aggressiveness of tumors and a worse patient
      prognosis. This makes the simultaneous targeting of two surface receptors by
      using bispecific constructs an increasingly appreciated strategy. Here, we have
      generated six such bispecific targeting proteins, each comprising two monomeric
      affibody molecules with specific binding to either of the two human epidermal
      growth factor receptors, EGFR and HER2, respectively. The bispecific constructs
      were designed with (i) alternative positioning (N- or C-terminal) of the
      different affibody molecules, (ii) two alternative peptide linkers (Gly(4)Ser)(3)
      or (Ser(4)Gly)(3), and (iii) affibody molecules with different affinity
      (nanomolar or picomolar) for HER2. Using both Biacore technology and cell binding
      assays, it was demonstrated that all six constructs could bind simultaneously to
      both their target proteins. N-terminal positioning of the inherent monomeric
      affibody molecules was favorable to promote the binding to the respective target.
      Interestingly, bispecific constructs containing the novel (Ser(4)Gly)(3) linker
      displayed a higher affinity in cell binding, as compared to constructs containing
      the more conventional linker, (Gly(4)Ser)(3). It could further be concluded that
      bispecific constructs (but not the monomeric affibody molecules) induced dimer
      formation and phosphorylation of EGFR in SKBR3 cells, which express fairly high
      levels of both receptors. It was also investigated whether the bispecific binding
      would influence cell growth or sensitize cells for ionizing radiation, but no
      such effects were observed.

PMID- 22882003
TI  - Prophylactic attempt at manual rotation in brow presentation at full dilatation.
AB  - We report our management of brow presentation at full dilatation by a
      prophylactic attempt at manual rotation or immediate cesarean delivery, depending
      on practitioner training. During the study period, 49 women with brow
      presentation were collected for an overall 30 452 deliveries (1/621) and 22
      (44.9%) of them were diagnosed at full dilatation. For the latter, an attempt at
      manual rotation was performed in 13 cases (59.1%) with no particular maternal or
      neonatal complications reported and vaginal delivery occurred in 10 (76.9%).
      Maternal and neonatal outcomes were similar between women with immediate cesarean
      section or prophylactic manual rotation, except for a shorter duration of
      hospitalization in the group with attempted manual rotation (p < 0.01).
      Prophylactic attempted manual rotation in brow presentation diagnosed at full
      dilatation may be associated with a high rate of vaginal delivery with no
      specific maternal or neonatal complications.

PMID- 22882001
TI  - Spatially resolved genomic, stable isotopic, and lipid analyses of a modern
      freshwater microbialite from Cuatro Cienegas, Mexico.
AB  - Microbialites are biologically mediated carbonate deposits found in diverse
      environments worldwide. To explore the organisms and processes involved in
      microbialite formation, this study integrated genomic, lipid, and both organic
      and inorganic stable isotopic analyses to examine five discrete depth horizons
      spanning the surface 25 mm of a modern freshwater microbialite from Cuatro
      Cienegas, Mexico. Distinct bacterial communities and geochemical signatures were
      observed in each microbialite layer. Photoautotrophic organisms accounted for
      approximately 65% of the sequences in the surface community and produced biomass
      with distinctive lipid biomarker and isotopic (delta(13)C) signatures. This
      photoautotrophic biomass was efficiently degraded in the deeper layers by
      heterotrophic organisms, primarily sulfate-reducing proteobacteria. Two spatially
      distinct zones of carbonate precipitation were observed within the microbialite,
      with the first zone corresponding to the phototroph-dominated portion of the
      microbialite and the second zone associated with the presence of sulfate-reducing
      heterotrophs. The coupling of photoautotrophic production, heterotrophic
      decomposition, and remineralization of organic matter led to the incorporation of
      a characteristic biogenic signature into the inorganic CaCO(3) matrix. Overall,
      spatially resolved multidisciplinary analyses of the microbialite enabled
      correlations to be made between the distribution of specific organisms,
      precipitation of carbonate, and preservation of unique lipid and isotopic
      geochemical signatures. These findings are critical for understanding the
      formation of modern microbialites and have implications for the interpretation of
      ancient microbialite records.

PMID- 22882004
TI  - Development of novel bisphosphonate prodrugs of doxorubicin for targeting bone
      metastases that are cleaved pH dependently or by cathepsin B: synthesis, cleavage
      properties, and binding properties to hydroxyapatite as well as bone matrix.
AB  - Bone metastases are a frequent cause of morbidity in cancer patients. The present
      palliative therapeutic options are chemotherapy, hormone therapy, and the
      administration of bisphosphonates. The affinity between bisphosphonates and the
      apatite structure of bone metastases is strong. Thus, we designed two low
      molecular-weight and water-soluble prodrugs which incorporate a bisphosphonate
      group as a bone targeting ligand, doxorubicin as the anticancer agent, and either
      an acid-sensitive bond (1) or a cathepsin B cleavable bond (3) for ensuring an
      effective release of doxorubicin at the site of action. Cleavage studies of both
      prodrugs showed a fast release of doxorubicin but sufficient stability over
      several hours in human plasma. Effective binding of prodrug 1 and 3 was
      demonstrated with hydroxyapatite and with native bone. In orientating toxicity
      studies in nude mice, the MTD of 1 was 3-fold higher compared to conventional
      doxorubicin, whereas 3 showed essentially the same MTD as doxorubicin.

PMID- 22882005
TI  - Interictal magnetoencephalography used in magnetic resonance imaging-negative
      patients with epilepsy.
AB  - PURPOSE: This study aims to investigate the contributions of
      magnetoencephalography (MEG) in magnetic resonance imaging (MRI)-negative
      patients. METHODS: A total of 18 MRI-negative patients diagnosed with refractory
      epilepsy, subjected to MEG investigation, and subsequently underwent surgery were
      selected for retrospective analysis. A 1.5-tesla Magnetom Sonata with an eight
      channel head array coil was used. MEG data were obtained using a 74/248-channel
      system. RESULTS: A total of 16 patients (16/18) had positive MEG results,
      comprising 12 patients with monofocal localizations, five with multifocal
      localizations, and one with unremarkable results in MEG. In addition, 12 patients
      had indicative single photon-emission computed tomography (SPECT), five had
      indicative fluorodeoxyglucose positron emission tomography (FDG-PET), and all the
      patients had intracranial electroencephalography (EEG) (14 with subdural
      electrodes and four with electrocorticography). The intracranial EEG recordings
      of nine patients were guided by MEG informative results. Among these 18 patients,
      10 exhibited good postoperative outcomes (Engel I and II), four of which were
      completely seizure-free. All these ten patients had clear monofocal localization
      in MEG, including nine with accordant indicative metabolic changes in either
      SPECT or FDG-PET, or both. None of the five patients with multifocal
      localizations achieved good postoperative outcomes. CONCLUSION: For cases with
      negative MRI findings, epilepsy surgery may be an alternative option for pharmaco
      resistant patients if epileptogenic focus localizations by MEG are present in
      multimodal evaluation.

PMID- 22882007
TI  - Intraoperative subconjunctival bevacizumab as an adjunctive treatment in primary
      pterygium: a preliminary report.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of intraoperative
      subconjunctival bevacizumab as an adjunctive treatment after surgical excision of
      primary pterygium. PATIENTS AND METHODS: This was a randomized prospective
      clinical study. Group 1 (21 eyes) underwent pterygium excision with conjunctivo
      limbal autograft. Group 2 (20 eyes) received subconjunctival 1.25 mg/0.05 mL of
      bevacizumab at the end of the surgery. RESULTS: There were no statistically
      significant differences regarding age, sex, laterality, or dimensions of the
      pterygia or grafts between the two groups (P > .05, 95% confidence interval).
      After 8 months of follow-up, two eyes in group 1 and four eyes in group 2 had
      recurrent pterygia. One patient in group 2 had lost graft. The difference in
      recurrence rate between the two groups did not reach statistical significance (P
      = 0.4, 95% confidence interval). CONCLUSION: Intraoperative subconjunctival
      bevacizumab following primary pterygium surgical excision is not helpful and
      possibly harmful. Larger studies are needed.

PMID- 22882008
TI  - The association between retinal vessel morphology and retinal nerve fiber layer
      thickness in an elderly population.
AB  - BACKGROUND AND OBJECTIVE: To investigate the relationship between retinal vessel
      morphology (branching coefficient, bifurcation angle, and fractal analysis) and
      retinal nerve fiber layer (RNFL) thickness in an elderly population. PATIENTS AND
      METHODS: One hundred and one participants from the Lothian Birth Cohort 1936
      (population of people all born in 1936) were studied. RNFL thickness measurements
      (using optical coherence tomography [OCT]) and digital retinal photographs were
      collected. The retinal images were analyzed using custom-designed software called
      the Vascular Assessment and Measurement Platform for Images of the Retina.
      RESULTS: Greater deviation from the optimal arteriolar branching coefficient was
      associated with greater RNFL thickness (r = 0.249, P = .028). There was no
      significant association between RNFL thickness and the other retinal vessel
      morphology parameters. CONCLUSION: RNFL thickness increased significantly with
      suboptimality of arteriole branching coefficient. These findings cannot be
      explained by our current understanding of OCT. OCT-based biomarker metrics
      require further study to better define retinal neurovascular imaging and anatomy.

PMID- 22882009
TI  - Structural and thermal characterization of wheat straw pretreated with aqueous
      ammonia soaking.
AB  - Production of renewable fuels and chemicals from lignocellulosic feedstocks
      requires an efficient pretreatment technology to allow ready access of
      polysaccharides for cellulolytic enzymes during saccharification. The effect of
      pretreatment on wheat straw through a low-temperature and low-pressure soaking
      aqueous ammonia (SAA) process was investigated in this study using Fourier
      transform infrared (FTIR), pyrolysis-gas chromatography/mass spectroscopy (Py
      GC/MS), solid and liquid state nuclear magnetic resonance (NMR), and
      thermogravimetry/differential thermogravimetry (TG/DTG) to demonstrate the
      changes in lignin, hemicellulose, and cellulose structure. After treatment of 60
      mesh wheat straw particles for 60 h with 28-30% ammonium hydroxide (1:10
      solid/liquid) at 50  degrees C, sugar recovery increased from 14% (untreated) to
      67% (SAA treated). The FTIR study revealed a substantial decrease in absorbance
      of lignin peaks. Solid and liquid state NMR showed minimal lignin structural
      changes with significant compositional changes. Activation energy of control and
      pretreated wheat straw was calculated according to the Friedman and ASTM methods
      and found to be decreased for SAA-treated wheat straw, from 259 to 223 kJ/mol.
      The SAA treatment was shown to remove significant amounts of lignin without
      strongly affecting lignin functional groups or structure.

PMID- 22882011
TI  - Chukrasones A and B: potential Kv1.2 potassium channel blockers with new
      skeletons from Chukrasia tabularis.
AB  - Two new limonoids, chukrasone A (1) incorporating a highly rearranged A/B ring
      system and chukrasone B (2) possessing the first 16,19-dinor limonoid backbone
      with an extended C3 unit at C-15, were isolated from Chukrasia tabularis. Their
      structures were characterized on the basis of detailed spectroscopic analysis.
      Compounds 1 and 2 exhibited potential inhibition of the delayed rectifier (I(K))
      K(+) current.

PMID- 22882012
TI  - The diameter of coronary arteries in healthy newborns at birth, 1 and 6 months of
      ages.
AB  - OBJECTIVE: The aim of this study was to determine accurate and validated Z-score
      equations for the normal values of coronary diameters adjusted with growth
      changes of the neonates by testing three different time periods. METHODS:
      Echocardiography was performed on 200 healthy neonates at birth, 1 and 6 months
      of ages. Several regression models for the left (LCA) and right coronary artery
      (RCA) diameters were tested with weight, height, body surface area and aortic
      annulus diameter. Reliable standards for the coronary artery diameters for
      healthy newborns by determining Z-score equations with appropriate statistical
      validations were established. RESULTS: The coronary diameters on birth
      measurements were strongly correlated with birth weight, height, surface area and
      the diameter of the aortic annulus (Pearson's R > 0.8, all p < 0.01). There were
      significant associations between the mean data of weight, height, body surface
      area, aortic annulus and the LCA and RCA diameters measurements of study subjects
      at birth, 1 and 6 months of ages (p < 0.05). Z-score graphs of coronary artery
      diameters and weight of the subjects at three different time (LCA vs. weight at
      birth, R = 0.82, p < 0.001; LCA vs. weight at 1 month, R = 0.64, p < 0.001; LCA
      vs. weight at 6 months, R = 0.55, p < 0.001; RCA vs. weight at birth, R = 0.80, p
      < 0.001; RCA vs. weight at 1 month, R = 0.59, p < 0.001; RCA vs. weight at 6
      months, R = 0.49, p < 0.001) were constructed. CONCLUSION: We present a new set
      of equations for neonatal Z-score calculation on the basis of a large number of
      healthy neonates on three different time period consisting of birth, 1 and 6
      months of ages. It is clear with this study that the growth in caliber of the
      coronary arteries is definite and progressive during postnatal time.

PMID- 22882013
TI  - Effect of phosphate on the particle size of ferric oxyhydroxides anchored onto
      activated carbon: As(V) removal from water.
AB  - The surface area of iron oxyhydroxides is a key factor when removing As from
      water. However, research related to this matter shows that this issue has not
      been explored in detail. The use of capping agents is a viable method to
      synthesize ferric oxyhydroxide nanoparticles; however, this method to our
      knowledge has not been applied for the anchorage of iron oxyhydroxide
      nanoparticles on activated carbon (AC). In the present work, the addition of
      PO(4) (as a capping agent) in forced hydrolysis of FeCl(3) in AC was
      investigated. Results revealed that the surface area of modified materials
      reached a maximum of about 900 m(2)/g with a molar ratio PO(4)/Fe of 0.1.
      Moreover, microscopy studies indicate a size range of iron nanoparticles from 2
      to 300 nm, where the smallest particles are attained with the highest
      concentration of PO(4). The surface charge distribution of modified samples
      became less positive; however, the As removal increased, indicating that
      electrostatic interaction is not the controlling sorption mechanism. Modified
      samples showed a 40% increase on As(V) adsorption capacity when using a molar
      ratio PO(4)/Fe of 1.5. The proposed method allowed anchoring of iron
      oxyhydroxides nanoparticles on AC, which have a high As(V) adsorption capacity (5
      mg/g).

PMID- 22882014
TI  - Beyond traits: personality as intersubjective themes.
AB  - The author argues that research in the idiographic tradition is more conducive to
      effective clinical work than the uncritical adoption of specific "evidence-based
      therapies" for discrete symptomatic disorders. She views pressures on therapists
      to adopt evidence-based therapies without consideration of individual differences
      and personal subjectivity as the misapplication of a research paradigm to the
      clinical situation. Reviewing some recent empirical work on individuality and
      therapeutic process, she critiques efforts to formulate personality diagnosis on
      the basis of externally observable traits without attention to internal
      experience, and she contends that intrapsychic themes account for personality
      differences more powerfully than traits, even when traits are construed
      dimensionally.

PMID- 22882016
TI  - Localized emitting state and energy transfer properties of quadrupolar
      chromophores and (multi)branched derivatives.
AB  - In order to better understand the nature of intramolecular charge and energy
      transfer in multibranched molecules, we have synthesized and studied the
      photophysical properties of a monomer quadrupolar chromophore with donor-acceptor
      donor (D-A-D) electronic push-pull structure, together with its V-shaped dimer
      and star-shaped trimers. The comparison of steady-state absorption spectra and
      fluorescence excitation anisotropy spectra of these chromophores show evidence of
      weak interaction (such as charge and energy transfer) among the branches.
      Moreover, similar fluorescence and solvation behavior of monomer and branched
      chromophores (dimer and trimer) implies that the interaction among the branches
      is not strong enough to make a significant distinction between these molecules,
      due to the weak interaction and intrinsic structural disorder in branched
      molecules. Furthermore, the interaction between the branches can be enhanced by
      inserting pi bridge spacers (-C?C- or -C=C-) between the core donor and the
      acceptor. This improvement leads to a remarkable enhancement of two-photon cross
      sections, indicating that the interbranch interaction results in the
      amplification of transition dipole moments between ground states and excited
      states. The interpretations of the observed photophysical properties are further
      supported by theoretical investigation, which reveal that the changes of the
      transition dipole moments of the branched quadrupolar chromophores play a
      critical role in observed the two-photon absorption (2PA) cross-section for an
      intramolecular charge transfer (ICT) state interaction in the multibranched
      quadrupolar chromophores.

PMID- 22882015
TI  - Practitioner review: Children in foster care--vulnerabilities and evidence-based
      interventions that promote resilience processes.
AB  - BACKGROUND: An increasing number of children are placed in foster care (i.e., a
      kin or nonkin family home other than the biological parent) due to experiences of
      physical, sexual, emotional, or psychological abuse, and/or neglect. Children in
      foster care are at increased risk for a host of negative outcomes encompassing
      emotional, behavioral, neurobiological, and social realms. METHODS: Areas of risk
      and vulnerability among foster children are described, including emotional and
      behavioral deficits, impaired neurobiological development, and social
      relationship deficits. Evidence suggesting the significance of family placement
      changes and prenatal exposure to substances as contributing mechanisms is
      presented. Based on a systematic search of the PsycINFO database (to March 2012),
      eight efficacious evidence-based interventions for foster families are
      summarized. FINDINGS: Although the development of evidence-based interventions
      that improve outcomes for foster children has lagged behind the delivery of
      interventions in other service sectors (e.g., mental health and educational
      sectors), several interventions across childhood and adolescence offer promise.
      Service system constraints offer both challenges and opportunities for more
      routine implementation of evidence-based interventions. CONCLUSIONS: Given the
      increased likelihood of poor outcomes for foster children, increased efforts to
      understand the pathways to vulnerability and to implement interventions shown to
      be effective in remediating risks and improving outcomes for this population are
      indicated. Evaluation of efficacious interventions in countries outside of the
      United States is also needed.

PMID- 22882017
TI  - Electronic excitations in epicocconone analogues: TDDFT methodological assessment
      guided by experiment.
AB  - In this work we present a combined theoretical and experimental study of UV/vis
      absorption spectra of novel organic chromophores derived from epicocconone. A
      computational protocol, consistent with experimental findings, is proposed in the
      framework of time-dependent density functional theory. More precisely, the
      influence of density functional, basis set, and solvation effects is assessed
      through theory-experiment matching. On the one hand, it is shown that global
      hybrid functionals fail to describe excitation spectra for the whole training
      set. On the other hand, range-separated hybrids allow a description of the
      complete set of epicocconone derivatives on equal footing, while the double-zeta
      basis set is shown to be sufficiently accurate for the screening of the
      spectroscopic properties in epicocconone analogues. The inclusion of solvent
      effects within a polarizable continuum model appears to be compulsory to decrease
      the residual dispersion. State specific solvation, on the contrary, does not
      provide a significant consistency/accuracy improvement. Besides, conformational
      transformations in investigated compounds and their influence on electronic
      absorption spectra are pointed out. A systematic choice of the same conformation
      for each compound from the training set enhances consistency and accuracy of our
      theoretical model. Lastly, a TDDFT-based calibration is proposed for prediction
      of absorption wavelengths in epicocconone analogues.

PMID- 22882018
TI  - Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients
      with focal-onset seizures: integrated analysis of pooled data from double-blind
      phase III clinical studies.
AB  - PURPOSE: To evaluate the efficacy and safety profile of eslicarbazepine acetate
      (ESL) added to stable antiepileptic therapy in adults with partial-onset
      seizures. METHODS: Data from 1,049 patients enrolled from 125 centers, in 23
      countries, in three phase III double-blind, randomized, placebo-controlled
      studies were pooled and analyzed. Following a 2-week titration period, ESL was
      administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. KEY
      FINDINGS: Seizure frequency was significantly reduced with ESL 800 mg (p <
      0.0001) and 1,200 mg (p < 0.0001) compared to placebo. Median relative reduction
      in seizure frequency was, respectively, 35% and 39% (placebo 15%) and responder
      rate was 36% and 44% (placebo 22%). ESL was more efficacious than placebo
      regardless of gender, geographic region, epilepsy duration, age at time of
      diagnosis, seizure type, and number and type of concomitant antiepileptic drugs
      (AEDs). Incidence of adverse events (AEs) and AEs leading to discontinuation were
      dose dependent. AEs occurred mainly during the first weeks of treatment, with no
      difference between groups after 6 weeks. Most common AEs (>10% patients) were
      dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared
      to placebo was generally consistent among different subpopulations. SIGNIFICANCE:
      Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy
      and safety end points. Results were independent of study population
      characteristics and type and number of concomitant AEDs.

PMID- 22882019
TI  - Glioblastoma brain tumours: estimating the time from brain tumour initiation and
      resolution of a patient survival anomaly after similar treatment protocols.
AB  - A practical mathematical model for glioblastomas (brain tumours), which
      incorporates the two key parameters of tumour growth, namely the cancer cell
      diffusion and the cell proliferation rate, has been shown to be clinically useful
      and predictive. Previous studies explain why multifocal recurrence is inevitable
      and show how various treatment scenarios have been incorporated in the model. In
      most tumours, it is not known when the cancer started. Based on patient in vivo
      parameters, obtained from two brain scans, it is shown how to estimate the time,
      after initial detection, when the tumour started. This is an input of potential
      importance in any future controlled clinical study of any connection between cell
      phone radiation and brain tumour incidence. It is also used to estimate more
      accurately survival times from detection. Finally, based on patient parameters,
      the solution of the model equation of the tumour growth helps to explain why
      certain patients live longer than others after similar treatment protocols
      specifically surgical resection (removal) and irradiation.

PMID- 22882020
TI  - A mathematical model of population dynamics for Batesian mimicry system.
AB  - We analyse a mathematical model of the population dynamics among a mimic, a
      corresponding model, and their common predator populations. Predator changes its
      search-and-attack probability by forming and losing its search image. It cannot
      distinguish the mimic from the model. Once a predator eats a model individual, it
      comes to omit both the model and the mimic species from its diet menu. If a
      predator eats a mimic individual, it comes to increase the search-and-attack
      probability for both model and mimic. The predator may lose the
      repulsive/attractive search image with a probability per day. By analysing our
      model, we can derive the mathematical condition for the persistence of model and
      mimic populations, and then get the result that the condition for the persistence
      of model population does not depend on the mimic population size, while the
      condition for the persistence of mimic population does depend the predator's
      memory of search image.

PMID- 22882021
TI  - Order of events matter: comparing discrete models for optimal control of species
      augmentation.
AB  - We investigate optimal timing of augmentation of an endangered/threatened species
      population in a target region by moving individuals from a reserve or captive
      population. This is formulated as a discrete-time optimal control problem in
      which augmentation occurs once per time period over a fixed number of time
      periods. The population model assumes the Allee effect growth functions in both
      target and reserve populations and the control objective is to maximize the
      target and reserve population sizes over the time horizon while accounting for
      costs of augmentation. Two possible orders of events are considered for different
      life histories of the species relative to augmentation time: move individuals
      either before or after population growth occurs. The control variable is the
      proportion of the reserve population to be moved to the target population. We
      develop solutions and illustrate numerical results which indicate circumstances
      for which optimal augmentation strategies depend upon the order of events.

PMID- 22882022
TI  - Estimating von Bertalanffy parameters with individual and environmental
      variations in growth.
AB  - Variation among individuals is an ubiquitous feature of natural populations.
      However, the relative roles of intrinsic individual differences and stochastic
      processes in generating variation remain poorly understood. For somatic growth,
      identifying the contribution of individual and stochastic processes to observed
      variation in size has important implications both for basic and applied biology.
      Here we propose and develop methods for estimating individual variation in growth
      using size-at-age data. We modify the von Bertalanffy growth model to explicitly
      incorporate individual, environmental, and stochastic variation and provide
      analytic expressions for the mean and variance of length-at-age in populations.
      We use a Bayesian statistical model to estimate individual variation from length
      at-age data and apply the model to simulated data to test its efficacy. Although
      a first step towards understanding individual variation, we demonstrate that
      estimating individual variation from observational samples is possible and
      provide a platform for future analytical and statistical developments.

PMID- 22882073
TI  - Novel targeted therapies and combinations for the treatment of multiple myeloma.
AB  - Multiple myeloma is a B-cell neoplasm that is characterized by clonal
      proliferation of terminally differentiated plasma cells. Approximately 20,000 new
      cases are diagnosed each year with a prevalence of about 60,000. Characteristic
      clinical features include bone disease, hypercalcemia, renal disease, anemia and
      infections. Advancements in our understanding of multiple myeloma have led to a
      significant impact in the natural history of the disease. Despite these advances
      the disease remains incurable and most patients invariably relapse and die. Our
      understanding of the transformation of normal plasma cells into myeloma cells and
      the interaction between myeloma cells and elements of the bone marrow
      microenvironment that sustain proliferation and survival has significantly
      improved. This knowledge has paved the way for the development of novel drugs
      that target the genetic and molecular changes that underlie myeloma
      pathophysiology. In this review we discuss several of these novel agents. We
      focus on the specific pathways targeted by these drugs and the role they may play
      in development or progression of multiple myeloma. We also discuss the proposed
      mechanism of action of these drugs and correlate these to clinical trials where
      they have been investigated.

PMID- 22882023
TI  - ONO-2506 inhibits spike-wave discharges in a genetic animal model without
      affecting traditional convulsive tests via gliotransmission regulation.
AB  - BACKGROUND AND PURPOSE: Anticonvulsants have been developed according to the
      traditional neurotransmission imbalance hypothesis. However, the anticonvulsive
      pharmacotherapy currently available remains unsatisfactory. To develop new
      antiepileptic drugs with novel antiepileptic mechanisms, we have tested the
      antiepileptic actions of ONO-2506, a glial modulating agent, and its effects on
      tripartite synaptic transmission. EXPERIMENTAL APPROACH: Dose-dependent effects
      of ONO-2506 on maximal-electroshock seizure (MES), pentylenetetrazol-induced
      seizure (PTZ) and epileptic discharge were determined in a genetic model of
      absence epilepsy in mice (Cacna1a(tm2Nobs/tm2Nobs)  strain). Antiepileptic
      mechanisms of ONO-2506 were analysed by examining the interaction between ONO
      2506 and transmission-modulating toxins (tetanus toxin, fluorocitrate,
      tetrodotoxin) on release of l-glutamate, d-serine, GABA and kynurenic acid in the
      medial-prefrontal cortex (mPFC) of freely moving rats using microdialysis and
      primary cultured rat astrocytes. KEY RESULTS: ONO-2506 inhibited spontaneous
      epileptic discharges in Cacna1a(tm2Nobs/tm2Nobs)  mice without affecting MES or
      PTZ. Given systemically, ONO-2506 increased basal release of GABA and kynurenic
      acid in the mPFC through activation of both neuronal and glial exocytosis, but
      inhibited depolarization-induced releases of all transmitters. ONO-2506 increased
      basal glial release of kynurenic acid without affecting those of l-glutamate, d
      serine or GABA. However, ONO-2506 inhibited AMPA-induced releases of l-glutamate,
      d-serine, GABA and kynurenic acid. CONCLUSIONS AND IMPLICATIONS: ONO-2506 did not
      affect traditional convulsive tests but markedly inhibited epileptic phenomena in
      the genetic epilepsy mouse model. ONO-2506 enhanced release of inhibitory neuro-
      and gliotransmitters during the resting stage and inhibited tripartite
      transmission during the hyperactive stage. The results suggest that ONO-2506 is a
      novel potential glial-targeting antiepileptic drug. LINKED ARTICLE: This article
      is commented on by Onat, pp. 1086-1087 of this issue. To view this commentary
      visit http://dx.doi.org/10.1111/bph.12050.

PMID- 22882074
TI  - Modulation of cardiovascular function by adipokines.
AB  - Cardiovascular disease (CVD) and associated risk factors such as obesity remain
      at the forefront of health concerns. Adipose tissue has been well established as
      an endocrine organ that becomes dysfunctional with increased adipose tissue mass.
      The secretion of several adipokines is altered in subjects with abdominal
      adiposity and these changes to the endocrine balance may contribute to increased
      CVD risk. The identification and characterization of disease-specific proteins
      within the adipose tissue offers a novel therapeutic target for prevention or
      treatment of cardiovascular complications. This review will discuss the latest
      developments on therapeutic targets within the context of adipokines, such as
      adiponectin, C1q/ tumor necrosis factor (TNF) related proteins (CTRPs), visfatin,
      vaspin, chemerin and omentin, and their involvement in obesity-related
      cardiovascular complications.

PMID- 22882075
TI  - Patterns of dental service utilization following nontraumatic dental condition
      visits to the emergency department in Wisconsin Medicaid.
AB  - OBJECTIVES: To examine patterns of dental service utilization for adult Medicaid
      enrollees in Wisconsin following nontraumatic dental condition (NTDC) visits to
      the emergency department (ED). METHODS: This is a retrospective, observational
      study of claims for NTDC visits to the ED and dental service encounters from the
      Wisconsin Medicaid Evaluation and Decision Support database (2001-2009). We used
      competing risk models to predict probabilities of returning to the ED versus
      obtaining follow-up care from a dentist. RESULTS: We observed a 43 percent
      increase in the rate of NTDC visits to the ED, with most of this increase
      occurring from 2001 to 2005. Within 30 days of an NTDC visit to the ED, ~29.6
      percent of enrollees will first visit a dentist office, while ~9.9 percent will
      return to the ED. Young to middle-aged adults (18 to <50 years) and enrollees
      living in counties with a lower supply of dental providers were more likely to
      return to the ED following a NTDC visit. Among the enrollees that first visited a
      dental office following an ED visit, 37.6 percent had an extraction performed at
      this visit. CONCLUSIONS: Almost one in five adult Medicaid enrollees will
      subsequently return to the ED following a previous NTDC visit. The provision of
      definitive care for these individuals appears to primarily consist of
      extractions.

PMID- 22882076
TI  - Hematological and biochemical blood values in wild populations of black howler
      monkeys (Alouatta pigra) of Campeche, Mexico.
AB  - BACKGROUND: The clinical analyses of free-ranging New World primates are
      extremely limited. The aim of this study was to obtain baseline data of blood
      chemistry and hematological values of free-ranging Alouatta pigra. METHOD: 17
      males and 17 females were captured. We collected blood from the caudal tail vein;
      conventional techniques were used to analyze the samples RESULTS: Hemoglobin,
      hematocrit, and erythrocytes were significantly higher in males than in females.
      In relation to biochemical blood values, albumin/globulin ratio, cholesterol,
      triglycerides, calcium, phosphorus, magnesium, and iron were significantly higher
      in males than in females, while creatinine was significantly higher in females
      than in males. CONCLUSIONS: In general, measured parameters are similar to those
      of other primates and will be used as reference values for futures studies.

PMID- 22882077
TI  - Signal amplification of graphene oxide combining with restriction endonuclease
      for site-specific determination of DNA methylation and assay of methyltransferase
      activity.
AB  - Site-specific identification of DNA methylation and assay of MTase activity are
      important in determining specific cancer types, providing insights into the
      mechanism of gene repression, and developing novel drugs to treat methylation
      related diseases. This work reports an electrochemical method for gene-specific
      methylation detection and MTase activity assay using HpaII endonuclease to
      improve selectivity and employing signal amplification of graphene oxide (GO) to
      enhance the assay sensitivity. The method was developed by designing a probe DNA,
      which was immobilized on electrode surface, to hybridize with target DNA (one 137
      mer DNA from exon 8 promoter region of the Homo sapiens p53 gene, was extracted
      from HCT116 cells). The assay is based on the electrochemical responses of the
      reporter (thionine), which was conjugated to 3'-terminus of the probe DNA via GO,
      after the DNA hybrid was methylated (under catalysis of M.SssI MTase) and cleaved
      by HpaII endonuclease (a site-specific endonuclease recognizing the duplex
      symmetrical sequence of 5'-CCGG-3' and catalyzing cleavage between the
      cytosines). This model can determine DNA methylation at the site of CpG and has
      an ability to discriminate the target DNA sequence from even single-base
      mismatched sequence. The electrochemical signal has a linear relationship with
      M.SssI activities ranging from 0.1 to 450 U/mL with a detection limit of ~(0.05
      +/- 0.02) U/mL at a signal/noise of 3. The advantages of this assay are ease of
      performance having a good specificity and selectivity. In addition, we also
      demonstrate the method can be used for rapid evaluation and screening of the
      inhibitors of MTase and has a potential application in discovery of new
      anticancer drugs.

PMID- 22882078
TI  - Nature of protein-CO2 interactions as elucidated via molecular dynamics.
AB  - Rising global temperatures require innovative measures to reduce atmospheric
      concentrations of CO(2). The most successful carbon capture technology on Earth
      is the enzymatic capture of CO(2) and its sequestration in the form of glucose.
      Efforts to improve upon or mimic this naturally occurring process will require a
      rich understanding of protein-CO(2) interactions. Toward that end, extensive all
      atom molecular dynamics (MD) simulations were performed on the CO(2)-utilizing
      enzyme phosphoenolpyruvate carboxykinase (PEPCK). Preliminary simulations were
      performed using implicit and explicit solvent models, which yielded similar
      results: arginine, lysine, tyrosine, and asparagine enhance the ability of a
      protein to bind carbon dioxide. Extensive explicit solvent simulations were
      performed for both wild-type PEPCK and five single-point PEPCK mutants, revealing
      three prevalent channels by which CO(2) enters (or exits) the active site cleft,
      as well as a fourth channel (observed only once), the existence of which can be
      rationalized in terms of the position of a key Arg residue. The strongest CO(2)
      binding sites in these simulations consist of appropriately positioned hydrogen
      bond donors and acceptors. Interactions between CO(2) and both Mn(2+) and Mg(2+)
      present in PEPCK are minimal due to the stable protein- and solvent-based
      coordination environments of these cations. His 232, suggested by X-ray
      crystallography as being a potential important CO(2) binding site, is indeed
      found to be particularly "CO(2)-philic" in these simulations. Finally, a recent
      mechanism, proposed on the basis of X-ray crystallography, for PEPCK active site
      lid closure is discussed in light of the MD trajectories. Overall, the results of
      this work will prove useful not only to scientists investigating PEPCK, but also
      to groups seeking to develop an environmentally benign, protein-based carbon
      capture, sequestration, and utilization system.

PMID- 22882079
TI  - Synthesis and evaluation of silanediols as highly selective uncompetitive
      inhibitors of human neutrophil elastase.
AB  - Chronic obstructive pulmonary disease (COPD) is an increasing health problem and
      is estimated to be the fifth leading cause of death in 2020 according to the
      World Health Organization. Current treatments are only palliative, and therefore
      the development of new medicine for the treatment of COPD is urgent. Human
      Neutrophil Elastase (HNE) is a serine protease that is heavily involved in the
      progression of COPD through inflammatory breakdown of lung tissue. Consequently,
      inhibitors of HNE are of great interest as therapeutics. In this article, the
      development of silanediol peptide isosters as inhibitors of HNE is presented.
      Kinetic studies revealed that incorporation of a silanediol isoster in the
      inhibitor structure resulted in an uncompetitive mechanism of inhibition, which
      further resulted in excellent selectivity. The peculiar mechanism of inhibition
      and the resulting selectivity makes the presented inhibitors promising leads for
      the development of new HNE-inhibitor-based therapeutics for the treatment of
      COPD.

PMID- 22882080
TI  - The revised COLIPA in vitro UVA method.
AB  - A multicentred study derived from the COLIPA in vitro UVA method was performed to
      assess the influence of test conditions on UVA protection factor (UVAPF) values
      in terms of amplitude, reproducibility between laboratories and correlation with
      in vivo UVA results. Eight products with a range of in vivo UVAPF from three to
      29 were used. Two different types of plates, namely high-roughness (5 MUm) and
      low-roughness (2 MUm) plates, were used with a different application rate for
      each (1.3 mg cm(-2)  and 0.75 mg cm(-2)  respectively). The UVR dose applied to
      both plate types followed the same principle as the original test (1.2 J. cm(-2) 
      * UVAPF0). Strong, significant correlations between in vitro and in vivo UVAPF
      values were observed for both plate types (Pearson correlation > 0.9, P <= 0.01).
      The correlation and slope obtained with the low-roughness plates confirmed the
      previous results obtained by COLIPA. Across all laboratories, higher UVAPF values
      were obtained on the high-roughness plates (P < 0.01). Reproducibility of UVAPF
      values between laboratories was comparable between the two plate roughness values
      (low roughness, COV = 8%; high roughness, COV = 12%). Considering the in vitro/in
      vivo comparisons, a regression slope of 0.83 was observed for the low-roughness
      plates, in comparison with a value of 1.05 for the high-roughness plates. The
      accuracy of the method was improved, therefore, with the use of the high
      roughness plates. With a constraint to recommend the use of only one plate type
      in the COLIPA UVA in vitro Test, the high-roughness plate was selected on an on
      going basis to limit variability of results and to provide better accuracy with
      in vivo data.

PMID- 22882081
TI  - Development of a sensitive cost-effective capture ELISA for detection of murine
      monoclonal antibodies: correlation with SPR biosensor technology.
AB  - The development of antibodies for diagnostic and therapeutic applications in
      inflammatory diseases is a major focus for biotechnology and pharmaceutical
      companies. Production of monoclonal antibodies requires the development of fast,
      high-throughput methodologies for screening and selecting appropriate candidate
      antibodies for development. Capture (sandwich) enzyme linked immunosorbent assay
      (ELISA) provides a quick and reliable method that could be used for hybridoma
      screening of potential candidates accompanied with surface plasmon resonance
      (SPR) biosensor technology for identifying high affinity biomolecular
      interactions. A sensitive, cost-effective, robust and accurate capture ELISA for
      detection of murine monoclonal antibodies in culture supernatants was developed.
      This assay was optimized for high sensitivity and specificity with a capture anti
      mouse polyclonal antibody. Using serial dilutions of a defined murine IgG
      antibody, a linear dose-response was observed between 2 and 1200 ng/ml antibody
      with a coefficient of determination r2 of 0.98. The detection limit of the assay
      was established as 2ng/ml (12.5pM). A similar concentration-dependent
      doseresponse was also observed using serial dilutions of antibody-containing
      supernatants from anti-alpha glycophorinproducing hybridomas (detection limit
      1:2000). Specific capture of antibodies from supernatants in a similar setting
      was also confirmed using SPR biosensor technology and correlated well with the
      immunoassay results. The latter technology can be performed in order to provide
      quick screening results and kinetic analysis of antibody binding interactions
      aiming at identifying candidates with high affinity and specificity.

PMID- 22882082
TI  - Novel piperazinyl derivatives with anti-hyperalgesic, anti-allodynic and anti
      inflammatory activities useful for the treatment of Neuropathic Pain.
AB  - A series of structurally novel compounds possessing 2-phenylpiperazin-1-yl
      nicotinamide template was synthesized and evaluated for neuropathic pain
      activity. After the assessment of neurotoxicity and peripheral analgesic
      activity, the compounds were evaluated in a peripheral neuropathic pain model,
      the chronic constriction injury (CCI) to assess their antiallodynic and
      antihyperalgesic potential. Studies carried out to assess the underlying
      mechanism revealed that the compounds (5 and 6) suppressed the inflammatory
      component of the neuropathic pain and inhibited oxidative and nitrosative stress.

PMID- 22882083
TI  - In vitro comparative evaluation of non-leaves and leaves extracts of Andrographis
      paniculata on modulation of inflammatory mediators.
AB  - This study was designed to evaluate and compare the inhibitory property of
      extracts of Andrographis paniculata leaves [methanolic (AP1), hydroalcoholic
      (AP2), successive water (AP3)] and non-leaves [methanolic (AP4), hydroalcoholic
      (AP5), successive water (AP6)] towards inflammatory mediators (NO, IL-1 beta, IL
      6, TNF alpha, PGE2, TXB2 and LTB4). Stimulant induced J774A.1 murine macrophages
      and HL-60 promyelocytic leukemic cells were used to study the inhibitory
      potential of extracts of A. paniculata on inflammatory mediators. Results
      revealed that AP1 and AP4 exhibited inhibitory effect on all the inflammatory
      mediators excluding PGE2 and TNF-alpha. AP2 and AP5 exhibited inhibitory effect
      towards IL-1 beta, TXB2 and did not show inhibitory effect towards other
      mediators. However, AP3 and AP6 failed to show inhibitory activity against any of
      the inflammatory mediators at the tested concentrations. Further, we observed
      that the magnitude of inhibitory effect displayed by A. paniculata extracts
      depends on the andrographolide content, although, it does not appear to influence
      the inhibitory effect towards LTB4 production.

PMID- 22882084
TI  - Effects of the Start For Life treatment on physical activity in primarily African
      American preschool children of ages 3-5 years.
AB  - In U.S. children of ages 2-5 years, combined overweight and obesity has increased
      to 21%, with African American children of this age range highest at 26%. Lack of
      physical activity is highly predictive of overweight and obesity in children.
      Preschools may be a useful point for intervention. An innovative preschool
      physical activity treatment (Start For Life) was developed based on principles of
      social cognitive and self-efficacy theory. It incorporated 30 minutes daily of
      highly structured physical activity with behavioral and self-regulatory skills
      training (e.g. goal setting, self-monitoring, productive self-talk) interspersed.
      Data obtained from accelerometry was used to contrast physical activity outputs
      during the preschool day in the Start For Life condition (n = 202) with a usual
      care control condition (n = 136). After controlling for age and sex of the
      primarily African American participants (M age = 4.7 years), changes over eight
      weeks in moderate-to-vigorous and vigorous physical activity were significant,
      and significantly more favorable in the Start For Life group; F(1, 344) = 4.98, p
      = .026 and F(1, 344) = 3.60, p = .058, respectively. Start For Life was
      associated with a weekly increase in moderate-to-vigorous physical activity of
      approximately 40 minutes. After sufficient replications that better account for
      different sample types, parental effects and physical activity outside of the
      school day, and long-term effects, widespread dissemination may be considered.

PMID- 22882085
TI  - Finding the light at the end of the tunnel: age differences in the relation
      between internal states terms and coping with potential threats to self.
AB  - Previous research has examined how adults respond to negative self-evaluations,
      but has not explored developmental differences in this process. This cross
      sectional study investigated linkages between the inclusion of internal states
      language in narrative accounts of problems in important self-categories and
      reports of coping responses and troubling thoughts. There were a total of 160
      participants at three age levels: late childhood (9-12 years old), early
      adolescence (12-15 years old) and emerging adulthood (18-28 years old). Age
      related changes were found in the density of internal states language and its
      relation to coping strategies. Among the children, greater usage of positive
      emotion terms predicted less adaptive use of coping strategies. In contrast,
      among the adolescents, greater density of positive emotion terms and anxiety
      terms was associated with more assistance seeking, and greater use of anger terms
      was related to lower levels of intrusive and avoidant thoughts. Finally, among
      the emerging adults, a greater density of insight terms was associated with
      higher levels of intrusive thoughts. The findings are interpreted as indicating
      unique responses to self-threat at different points in the development of the
      self-concept. Further, they have implications for understanding inconsistent past
      findings regarding the relation between internal states language usage and well
      being.

PMID- 22882086
TI  - A template model for studying anticancer drug efflux transporter inhibitors in
      vitro.
AB  - Efflux transporters play an important role in drug absorption and also in
      multidrug resistance. ABCG2 (BCRP) is an efflux transporter conferring cross
      resistance to mitoxantrone (Mit), irinotecan (CPT11), and its active metabolite
      SN38. MBLI87, a new ABCG2 inhibitor has proven its efficacy against ABCG2
      mediated efflux in vitro and in vivo. This work aimed at modeling and quantifying
      the cellular interaction between MBLI87 and different substrates using a
      mechanistic template model. An in vitro competition experiment study was carried
      out with HEK293 cells overexpressing ABCG2 exposed to fixed concentrations of
      substrates (Mit, CPT11, SN38) and to MBLI87 at several concentration levels. A
      nonlinear mixed-effects transport inhibition model was developed to fit
      intracellular drug concentrations. In this model, drugs cross the cell membrane
      through passive diffusion, active drug efflux is ABCG2 mediated, interaction
      between substrates and inhibitor occurs within the transporter. The interaction
      was found to be noncompetitive. The MBLI87 Ki was estimated to 141 nm for Mit,
      289 nm for CPT11, and 1160 nm for SN38. The ratio of intrinsic transport
      clearance divided by diffusion clearance was estimated to 2.5 for Mit, 1.01 for
      CPT11, and 5.4 for SN38. The maximal increase in the intracellular substrate
      concentration that is possible to achieve by inhibition of the transporter was
      estimated to 1.5 for Mit, 0.1 for CPT11, and 4.4 for SN38. This mechanistic
      template model describes both drug accumulation and cellular transport, and the
      mixed-effects approach allows an estimation of intra- and interassay variability.
      This model is of great interest to study cytotoxic cellular pharmacokinetics.

PMID- 22882087
TI  - Multidose pharmacokinetics of orally administered florfenicol in the channel
      catfish (Ictalurus punctatus).
AB  - Plasma disposition of florfenicol in channel catfish was investigated after an
      oral multidose (10 mg/kg for 10 days) administration in freshwater at water
      temperatures ranging from 24.7 to 25.9  degrees C. Florfenicol concentrations in
      plasma were analyzed by means of liquid chromatography with MS/MS detection.
      After the administration of florfenicol, the mean terminal half-life (t(1/2)),
      maximum concentration at steady-state (Css (max)), time of Css (max) (T(max)),
      minimal concentration at steady-state (Css (min)), and Vc /F were 9.0 h, 9.72
      MUg/mL, 8 h, 2.53 MUg/mL, and 0.653 L/kg, respectively. These results suggest
      that florfenicol administered orally at 10 mg/kg body weight for 10 days could be
      expected to control catfish bacterial pathogens inhibited in vitro by a minimal
      inhibitory concentration value of <2.5 MUg/mL.

PMID- 22882089
TI  - Angiogenic factors in maternal circulation and preeclampsia with or without fetal
      growth restriction.
AB  - OBJECTIVE: To study associations of placental growth factor (PlGF) and soluble
      fms-like tyrosine kinase 1 (sFlt-1) in maternal circulation with the risk of
      preeclampsia with and without fetal growth restriction. DESIGN: Nested case
      control study. SETTING: A cohort of 29 948 pregnant women in Norway. SAMPLE:
      Cases were identified through linkage to the Medical Birth Registry of Norway. We
      selected 69 preterm and 36 term preeclampsia cases with delivery of a small-for
      gestational-age (SGA) infant, 83 preterm and 154 term preeclampsia cases without
      SGA delivery, and 384 normotensive controls. METHODS: We measured PlGF and sFlt-1
      in maternal serum samples from each trimester. MAIN OUTCOME MEASURES: Odds ratios
      of preeclampsia subtypes by tertile categories of PlGF and sFlt-1. RESULTS: Low
      (lowest third) PlGF and sFlt-1 levels in the first trimester, and low (lowest
      third) increase in PlGF and strong (highest third) increase in sFlt-1 from first
      to second trimester were associated with increased risk of preterm preeclampsia,
      both with and without SGA offspring. For term preeclampsia with SGA offspring,
      the associations were similar to the findings for preterm preeclampsia. For term
      preeclampsia without SGA offspring, low increase in PlGF from first to second
      trimester and high sFlt-1 in the third trimester were associated with increased
      risk. CONCLUSIONS: Low PlGF and high sFlt-1 levels in maternal circulation are
      associated with subsequent development of preeclampsia, regardless of whether
      fetal growth is affected or not. For term preeclampsia without fetal growth
      restriction, the imbalance in angiogenic factors seems to appear later in
      pregnancy than for preterm preeclampsia.

PMID- 22882090
TI  - Identification and relative-quantification of glycans by matrix-assisted laser
      desorption/ionization in-source decay with hydrogen abstraction.
AB  - The use of specific matrixes allows enhancing the scope of in-source decay (ISD)
      applications in matrix-assisted laser desorption/ionization (MALDI) thanks to the
      specificity of analyte-matrix chemistry. The use of an oxidizing matrix, 5
      nitrosalicylic acid (5-NSA), for MALDI-ISD of glycans is shown to promote
      fragmentation pathways involving radical precursors. Both glycosidic and cross
      ring cleavages are promoted by hydrogen abstraction from hydroxyl group of
      glycans by 5-NSA molecules. Cross-ring cleavage ions are potentially useful in
      linkage analysis, one of the most critical steps of glycan characterization.
      Moreover, we show here that isobaric glycans could be distinguished by structure
      specific ISD ions and that the molar ratio of glycan isomers in the mixture can
      be estimated from their fragment ions abundance. The use of 5-NSA also opens the
      possibility to perform pseudo-MS(3) analysis of glycans. Therefore, MALDI-ISD
      with 5-NSA is a useful method for identification of glycans and semiquantitative
      analysis of mixture of glycan isomers.

PMID- 22882088
TI  - Overexpression of chromatin assembly factor-1 p60, poly(ADP-ribose) polymerase 1
      and nestin predicts metastasizing behaviour of oral cancer.
AB  - AIMS: The natural history of oral squamous cell carcinomas (OSCCs) is variable
      and difficult to predict. This study aimed to assess the value of the expression
      of poly(ADP-ribose) polymerase 1 (PARP-1), chromatin assembly factor-1 (CAF
      1)/p60 and the stem cell markers CD133, CD166, CD44, CD44v6 and nestin as markers
      of outcome and progression-free survival in OSCC patients. METHODS: Clinical data
      were collected from 66 patients (41 male and 25 female, aged 29-92 years) who
      underwent surgery for OSCC of the tongue, floor, lips, and palate. During follow
      up (range: 12-131 months), 14 patients experienced relapse/metastasis and/or
      death. The study was performed by immunohistochemistry on paraffin-embedded
      tumour tissues, western blot analysis of tumour protein lysates and human cell
      lines, and RNA silencing assays. In addition, the human papillomavirus (HPV)
      status of primary tumours was evaluated by immunohistochemistry and viral
      subtyping. Univariate and multivariate analyses were performed to determine the
      correlation between these parameters and the clinical and pathological variables
      of the study population. RESULTS AND CONCLUSIONS: We found that a PARP-1(high)
      /CAF-1 p60(high) /nestin(high) phenotype characterized the OSCCs with the worst
      prognosis (all HPV-negative). This may be of benefit in clinical management,
      since radio-enhancing anti-PARP-1 and/or anti-CAF-1/p60 agents may allow
      radioresistance to be bypassed in the nestin-overexpressing, metastasizing OSCC
      cells.

PMID- 22882093
TI  - Transfusion medicine illustrated. Red blood cell anomalies in the context of
      hereditary pyropoikilocytosis.

PMID- 22882092
TI  - Dengue in the context of "safe blood" and global epidemiology: to screen or not
      to screen?

PMID- 22882095
TI  - High-resolution melting method for genotyping human platelet antigens on ITGB3
      Exon 11.

PMID- 22882096
TI  - Leukoreduced blood and sensitization of organ transplant candidates.

PMID- 22882098
TI  - Recovered hemoglobin and hemolysis in filtered or processed shed blood after
      total knee arthroplasty.

PMID- 22882101
TI  - Exponential error reduction in pretransfusion testing with automation.
AB  - BACKGROUND: Protecting the safety of blood transfusion is the top priority of
      transfusion service laboratories. Pretransfusion testing is a critical element of
      the entire transfusion process to enhance vein-to-vein safety. Human error
      associated with manual pretransfusion testing is a cause of transfusion-related
      mortality and morbidity and most human errors can be eliminated by automated
      systems. However, the uptake of automation in transfusion services has been slow
      and many transfusion service laboratories around the world still use manual blood
      group and antibody screen (G&S) methods. STUDY DESIGN AND METHODS: The goal of
      this study was to compare error potentials of commonly used manual (e.g., tiles
      and tubes) versus automated (e.g., ID-GelStation and AutoVue Innova) G&S methods.
      Routine G&S processes in seven transfusion service laboratories (four with manual
      and three with automated G&S methods) were analyzed using failure modes and
      effects analysis to evaluate the corresponding error potentials of each method.
      RESULTS: Manual methods contained a higher number of process steps ranging from
      22 to 39, while automated G&S methods only contained six to eight steps.
      Corresponding to the number of the process steps that required human
      interactions, the risk priority number (RPN) of the manual methods ranged from
      5304 to 10,976. In contrast, the RPN of the automated methods was between 129 and
      436 and also demonstrated a 90% to 98% reduction of the defect opportunities in
      routine G&S testing. CONCLUSION: This study provided quantitative evidence on how
      automation could transform pretransfusion testing processes by dramatically
      reducing error potentials and thus would improve the safety of blood transfusion.

PMID- 22882102
TI  - The association between socio-ecological factors and having an after-school
      physical activity program.
AB  - BACKGROUND: After-school physical activity (PA) programs promote PA among youth.
      Few studies have used socio-ecological health models to identify barriers and
      facilitators of after-school PA programs. This study examined which socio
      ecological factors are associated with having an after-school PA program.
      METHODS: A questionnaire was administered to key representatives of 114
      elementary and 129 secondary schools. The association between socio-ecological
      factors and having an after-school PA program was analyzed at school level.
      RESULTS: In both types of schools more knowledge about community schools was
      positively associated with having an after-school PA program (odds ratio [OR] =
      1.96; 95% confidence interval [CI] = 1.18-3.27; OR = 1.88; 95% CI = 1.27-2.80,
      respectively). In elementary schools, environmental factors associated with
      having an after-school PA program included PA facilities (OR = 4.98; 95% CI =
      1.08-23.05), a PA working group (OR = 3.37; 95% CI = 1.02-11.10), agreements with
      the community (OR = 1.60; 95% CI = 1.05-2.43), shortage of human resources (OR =
      0.57; 95% CI = 0.37-0.89) and lack of support from teachers (OR = 0.51; 95% CI =
      0.33-0.80). In secondary schools, environmental factors included the presence of
      a remunerated coordinator (OR = 5.12; 95% CI = 1.38-19.10) and partnerships with
      "sport and PA leaders" (OR = 3.54; 95% CI = 1.01-12.41). CONCLUSION: Having an
      after-school PA program was associated with personal and environmental factors,
      which supports the use of socio-ecological frameworks for explorative and
      intervention studies aiming to increase after-school PA programs.

PMID- 22882103
TI  - Does the school performance variable used in the International Health Behavior in
      School-Aged Children (HBSC) Study reflect students' school grades?
AB  - BACKGROUND: Given the pressure that educators and policy makers are under to
      achieve academic standards for students, understanding the relationship of
      academic success to various aspects of health is important. The international
      Health Behavior in School-Aged Children (HBSC) questionnaire, being used in 41
      countries with different school and grading systems, has contained an item
      assessing perceived school performance (PSP) since 1986. Whereas the test-retest
      reliability of this item has been reported previously, we determined its
      convergent and discriminant validity. METHODS: This cross-sectional study used
      anonymous self-report data from Austrian (N = 266), Norwegian (N = 240), and
      Canadian (N = 9,717) samples. Students were between 10 and 17 years old. PSP
      responses were compared to the self-reported average school grades in 6 subjects
      (Austria) or 8 subjects (Norway), respectively, or to a general, 5-category-based
      appraisal of most recent school grades (Canada). RESULTS: Correlations between
      PSP and self-reported average school grade scores were between 0.51 and 0.65,
      representing large effect sizes. Differences between the median school grades in
      the 4 categories of the PSP item were statistically significant in all 3 samples.
      The PSP item showed predominantly small associations with some randomly selected
      HBSC items or scales designed to measure different concepts. CONCLUSIONS: The PSP
      item seems to be a valid and useful question that can distinguish groups of
      respondents that get good grades at school from those that do not. The meaning of
      PSP may be context-specific and may have different connotations across student
      populations from different countries with different school systems.

PMID- 22882104
TI  - Cardiovascular risk factors and physical activity behavior among elementary
      school personnel: baseline results from the ACTION! worksite wellness program.
AB  - BACKGROUND: Although the prevalence of obesity is increasing during adulthood,
      there have been few assessments of obesity, cardiovascular risk factors, and
      levels of physical activity among adult elementary school staff. METHODS: Data
      were collected from 745 African-American and White female school personnel in a
      suburban school district in southeastern Louisiana as part of the baseline
      assessment before implementation of a program to improve eating and physical
      activity behaviors. Anthropometry, blood pressure, serum lipids and lipoproteins,
      and glucose were measured using established protocols. Physical activity was
      assessed by accelerometry. RESULTS: For both White and Black females, 30% were
      overweight (body mass index [BMI]) >=25 kg/m(2)  but <30 kg/m(2) ). Whereas 37%
      of White females were obese (BMI >= 30 kg/m(2) ), 61% of the Black females were
      obese. There was a positive association between BMI and other cardiovascular risk
      factors except for high-density lipoprotein cholesterol, where the association
      was negative. The mean number of minutes of daily moderate-to-vigorous physical
      activity was <1 minute per day and was lower for overweight and obese women than
      for normal weight women. CONCLUSIONS: School personnel in the study have adverse
      cardiovascular risk factors, including high rates of obesity and very low levels
      of physical activity. Because these individuals are often called upon to promote
      health for children, they are an important target population for wellness
      interventions.

PMID- 22882106
TI  - A longitudinal study of childhood obesity, weight status change, and subsequent
      academic performance in Taiwanese children.
AB  - BACKGROUND: This study examined the association among childhood obesity, weight
      status change, and subsequent academic performance at 6-year follow-up. METHODS:
      First-grade students from one elementary school district in Taichung City, Taiwan
      were followed for 6 years (N = 409). Academic performance was extracted from the
      school records at the end of each grade. Weight and height were measured at the
      beginning of each grade. A weight change variable was created based on each
      child's weight status difference at grades 1 and 6. A multivariate linear
      regression model for predicting academic performance at grade 6 was developed
      with adjustment for individual characteristics and family factors. A latent
      growth curve (LGC) showed the association between changes in body mass index
      (BMI) and in academic performance across a 6-year period. RESULTS: BMI in
      children increased significantly across 6 years. The rate of increase in BMI over
      6 years was higher for children with higher baseline BMIs than it was for
      children with lower baseline BMIs. However, BMI changes were not significantly
      associated with changes of academic performance. CONCLUSION: There was no
      significant relationship between initial obesity or change in weight status and
      subsequent academic performance. It appears that either being or becoming
      overweight/obese did not impact academic achievement for these Taiwanese
      children.

PMID- 22882105
TI  - HEALTHY study school food service revenue and expense report.
AB  - BACKGROUND: Food service directors have a concern that federal reimbursement is
      not meeting the demands of increasing costs of healthier meals. The purpose of
      this article is to report the food option changes and the annual revenues and
      expenses of the school food service environment. METHODS: The HEALTHY study was a
      3-year (2006 to 2009) randomized, cluster-designed trial conducted in 42 middle
      schools at 7 field centers. The schools selected had at least 50% of students who
      were eligible for free or reduced-price lunch or who belonged to a minority
      group. A randomly assigned half of the HEALTHY schools received a school health
      intervention program consisting of 4 integrated components: nutrition, physical
      activity, behavioral knowledge and skills, and social marketing. The nutrition
      component consisted of changing the meal plans to meet 5 nutrition goals. Revenue
      and expense data were collected from income statements, federal meal records, a
      la carte sale sheets, school store sale sheets, donated money/food records, and
      vending machines. RESULTS: Although more intervention schools reached the
      nutritional goals than control schools, revenues and expenses were not
      significantly different between groups. CONCLUSION: The HEALTHY study showed no
      adverse effect of school food policies on food service finances.

PMID- 22882107
TI  - An experimental assessment of physical educators' expectations and attitudes: the
      importance of student weight and gender.
AB  - BACKGROUND: At school, physical education (PE) teachers and coaches may be key
      supports for physical activity. Unfortunately, PE teachers may endorse negative
      stereotypes and attitudes toward overweight youth. These biases may influence the
      amount of instruction physical educators provide to students and their
      participation in PE or other physical activity. METHODS: This study assessed
      physical educators' (N = 162) ability and performance expectations, attributions,
      and attitudes toward overweight and non-overweight students. RESULTS: Physical
      educators endorsed inferior ability expectations for overweight students compared
      to non-overweight students. Poorer performance expectations were limited to
      overweight female targets, but when controlling for participant characteristics,
      this effect became marginally significant for overweight male targets. There was
      a trend such that participants endorsed more external attributions for the
      abilities and performance of overweight female students, yet this effect was
      reduced to marginal significance when controlling for participant
      characteristics. Participants endorsed more negative attitudes for both
      overweight males and females compared to non-overweight youth. CONCLUSIONS:
      Findings indicate that physical educators' expectations, attributions, and
      attitudes regarding students may be negatively influenced by youth body weight,
      and differ by student gender. The potential effect of physical educators' weight
      bias on adolescent participation in physical activity and its implications for
      students' physical health, academic achievement, and social development are
      discussed.

PMID- 22882108
TI  - Parliamentary inquiry into health promoting schools in Victoria: analysis of
      stakeholder views.
AB  - BACKGROUND: In 2009, the Victorian Parliament Legislative Assembly of Australia
      commissioned a Parliamentary Inquiry into the opportunities for schools to become
      a focus for promoting healthy community living. Submissions to the Inquiry varied
      widely in their positions about school health promotion. The aim of this review
      is to analyze the submissions to identify core themes in the debates about school
      health promotion and how stakeholders saw schools becoming a focus for promoting
      healthy communities. METHODS: Submissions (N = 159) were downloaded from the
      Inquiry website. Open coding was used to code the data. The codes were then
      refined into conceptual categories to create themes. The Inquiry's terms of
      reference were used as an organizing framework. RESULTS: Emergent themes included
      barriers and enablers to school health promotion including the need for stronger
      leadership from the Departments of Health (DoH) and Education and Early Childhood
      Development (DEECD). CONCLUSION: Rather than supporting the idea that schools
      could have a wider role in communities, submissions pointed to the acute need for
      increased resource allocation to support health promotion in schools, and for
      coordinated approaches with stronger leadership from the health and education
      sectors. Without these structures, schools can only address health in an ad hoc
      manner with limited resources, capacity, and outcomes.

PMID- 22882109
TI  - Qualitative and semiquantitative analysis of composite mixtures of antibodies by
      native mass spectrometry.
AB  - Native mass spectrometry was evaluated for the qualitative and semiquantitative
      analysis of composite mixtures of antibodies representing biopharmaceutical
      products coexpressed from single cells. We show that by using automated peak
      fitting of the ion signals in the native mass spectra, we can quantify the
      relative abundance of each of the antibodies present in mixtures, with an average
      accuracy of 3%, comparable to a cation exchange chromatography based approach
      performed in parallel. Moreover, using native mass spectrometry we were able to
      identify, separate, and quantify 9 antibodies present in a complex mixture of 10
      antibodies, whereas this complexity could not be unraveled by cation exchange
      chromatography. Native mass spectrometry presents a valuable alternative to
      existing analytical methods for qualitative and semiquantitative profiling of
      biopharmaceutical products. It provides both the identity of each species in a
      mixture by mass determination and the relative abundance through comparison of
      relative ion signal intensities. Native mass spectrometry is a particularly
      effective tool for characterization of heterogeneous biopharmaceutical products
      such as bispecific antibodies and antibody mixtures.

PMID- 22882110
TI  - The Bayesian microbial subtyping attribution model: robustness to prior
      information and a proposition.
AB  - Attributing foodborne illnesses to food sources is essential to conceive,
      prioritize, and assess the impact of public health policy measures. The Bayesian
      microbial subtyping attribution model by Hald et al. is one of the most advanced
      approaches to attribute sporadic cases; it namely allows taking into account the
      level of exposure to the sources and the differences between bacterial types and
      between sources. This step forward requires introducing type and source-dependent
      parameters, and generates overparameterization, which was addressed in Hald's
      paper by setting some parameters to constant values. We question the impact of
      the choices made for the parameterization (parameters set and values used) on
      model robustness and propose an alternative parameterization for the Hald model.
      We illustrate this analysis with the 2005 French data set of non-typhi
      Salmonella. Mullner's modified Hald model and a simple deterministic model were
      used to compare the results and assess the accuracy of the estimates. Setting the
      parameters for bacterial types specific to a unique source instead of the most
      frequent one and using data-based values instead of arbitrary values enhanced the
      convergence and adequacy of the estimates and led to attribution estimates
      consistent with the other models' results. The type and source parameters
      estimates were also coherent with Mullner's model estimates. The model appeared
      to be highly sensitive to parameterization. The proposed solution based on
      specific types and data-based values improved the robustness of estimates and
      enabled the use of this highly valuable tool successfully with the French data
      set.

PMID- 22882112
TI  - Psychogenic nonepileptic seizures: a current overview.
AB  - Psychogenic nonepileptic seizures (PNES) resemble epilepsy, but no
      pathophysiological explanation has been established. Although there have been
      recent advances in PNES research and various hypotheses as to the
      psychopathology, no theory has achieved general acceptance. In this overview of
      selected literature on PNES, we highlight the often contradictory findings that
      underline the challenges that confront both practitioner and researcher. We first
      provide a synopsis of the history, diagnosis, treatment, and outcomes, as well as
      patient characteristics of PNES and the relevance of communication in the
      clinical context. In the subsequent sections we discuss recent research that may
      advance the understanding and diagnosis of this disorder. These themes include
      the use of qualitative methods as a viable research option, the application of
      nonlinear methods to analyze heterogeneous observations during diagnosis, recent
      advances in neuroimaging of PNES, and the development of international databases.

PMID- 22882111
TI  - Neuropsychological correlates of emotional lability in children with ADHD.
AB  - BACKGROUND: Emotional lability (EL) is commonly seen in patients with attention
      deficit/hyperactivity disorder (ADHD). The reasons for this association remain
      currently unknown. To address this question, we examined the relationship between
      ADHD and EL symptoms, and performance on a range of neuropsychological tasks to
      clarify whether EL symptoms are predicted by particular cognitive and/or
      motivational dysfunctions and whether these associations are mediated by the
      presence of ADHD symptoms. METHODS: A large multi-site sample of 424 carefully
      diagnosed ADHD cases and 564 unaffected siblings and controls aged 6-18 years
      performed a broad neuropsychological test battery, including a Go/No-Go Task, a
      warned four-choice Reaction Time task, the Maudsley Index of Childhood Delay
      Aversion and Digit span backwards. Neuropsychological variables were aggregated
      as indices of processing speed, response variability, executive functions, choice
      impulsivity and the influence of energetic and/or motivational factors. EL and
      ADHD symptoms were regressed on each neuropsychological variable in separate
      analyses controlling for age, gender and IQ, and, in subsequent regression
      analyses, for ADHD and EL symptoms respectively. RESULTS: Neuropsychological
      variables significantly predicted ADHD and EL symptoms with moderate-to-low
      regression coefficients. However, the association between neuropsychological
      parameters on EL disappeared entirely when the effect of ADHD symptoms was taken
      into account, revealing that the association between the neuropsychological
      performance measures and EL is completely mediated statistically by variations in
      ADHD symptoms. Conversely, neuropsychological effects on ADHD symptoms remained
      after EL symptom severity was taken into account. CONCLUSIONS: The
      neuropsychological parameters examined, herein, predict ADHD more strongly than
      EL. They cannot explain EL symptoms beyond what is already accounted for by ADHD
      symptom severity. The association between EL and ADHD cannot be explained by
      these cognitive or motivational deficits. Alternative mechanisms, including
      overlapping genetic influences (pleiotropic effects) and/or alternative
      neuropsychological processes need to be considered.

PMID- 22882113
TI  - Basal cell carcinoma arising in association with trichoepithelioma in a case of
      Brooke-Spiegler syndrome with a novel genetic mutation in CYLD.

PMID- 22882114
TI  - Stillbirth and fetal growth restriction.
AB  - OBJECTIVE: To confirm the role of fetal growth restriction (FGR) as a cause of
      stillbirth, and to compare diagnostic accuracy of customized fetal growth and
      population-based standards in identifying FGR within a pathological population of
      early and late stillbirths. METHODS: Retrospective study on a cohort of 189
      stillbirths occurred in single pregnancy between January 2006 and September 2011.
      Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe
      classifications, were evaluated on the basis of fetal birthweight with both
      Tuscany population and Gardosi customized standards. Unexplained stillbirths have
      been classified as early or late depending on the gestational age of occurrence.
      RESULTS: Aberdeen-Wigglesworth classification, applied to the 189 cases of
      stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification
      left only 40 (21%). By applying population standards to the 94 unexplained
      stillbirths we have identified 31 FGRs (33% of sample), while customized
      standards identified 54 FGRs (57%). Customised standards identified a larger
      number of FGRs with respect to population standards during the third trimester
      (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54%
      respectively) (p = 0.05). CONCLUSIONS: Customized standards have a higher
      diagnostic accuracy in identifying FGRs especially during the third trimester.

PMID- 22882116
TI  - Copper(II)/iron(III) co-catalyzed intermolecular diamination of alkynes: facile
      synthesis of imidazopyridines.
AB  - A facile synthesis of imidazo[1,2-alpha]pyridines has been achieved by copper(II)
      and iron(III) co-catalyzed C-N bond formation. This reaction involves an
      intermolecular oxidative diamination of alkynes with high chemoselectivity and
      regioselectivity.

PMID- 22882115
TI  - Body esteem, peer difficulties and perceptions of physical health in overweight
      and obese urban children aged 5 to 7 years.
AB  - OBJECTIVE: To determine whether there is an association between body mass index
      (BMI) and body esteem in young overweight and obese urban children, and to test
      peer relationship difficulties and perceived physical health as mediators of this
      relationship. METHODS: Child self-reported body esteem, and parent-reported child
      peer relationship difficulties (being bullied by peers and peer rejection) and
      physical health perceptions were obtained from 218 overweight and obese children
      aged 5-7 years (81% racial/ethnic minority, M BMI = 25.3) and their primary
      caregivers. RESULTS: Higher BMI was associated with lower body esteem for both
      girls and boys. This relation was mediated by poor physical health for boys but
      not for girls. Peer relationship difficulties did not mediate the observed
      association between BMI and body esteem in either group; however, girls with
      higher BMI experienced more bullying and being bullied by peers was associated
      with lower body esteem in girls. CONCLUSIONS: Intervening with perceptions of
      physical health may buffer overweight and obese boys from developing low body
      esteem in early childhood.

PMID- 22882117
TI  - Piracetam-induced changes on the brainstem auditory response in anesthetized
      juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.
AB  - BACKGROUND: We describe two clinical cases and examine the effects of piracetam
      on the brainstem auditory response in infantile female rhesus monkeys (Macaca
      mulatta). RESULTS: We found that the interwave intervals show a greater reduction
      in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. DISCUSSION:
      In this report, we discuss the significance of these observations.

PMID- 22882118
TI  - Conformation and electronic population transfer in membrane-supported self
      assembled porphyrin dimers by 2D fluorescence spectroscopy.
AB  - Two-dimensional fluorescence spectroscopy (2D FS) is applied to determine the
      conformation and femtosecond electronic population transfer in a dimer of
      magnesium meso tetraphenylporphyrin. The dimers are prepared by self-assembly of
      the monomer within the amphiphilic regions of 1,2-distearoyl-sn-glycero-3
      phosphocholine liposomes. A theoretical framework to describe 2D FS experiments
      is presented, and a direct comparison is made between the observables of this
      measurement and those of 2D electronic spectroscopy (2D ES). The sensitivity of
      the method to varying dimer conformation is explored. A global multivariable
      fitting analysis of linear and 2D FS data indicates that the dimer adopts a "bent
      T-shaped" conformation. Moreover, the manifold of singly excited excitons
      undergoes rapid electronic dephasing and downhill population transfer on the time
      scale of ~95 fs. The open conformation of the dimer suggests that its self
      assembly is favored by an increase in entropy of the local membrane environment.

PMID- 22882119
TI  - A new class of selective and potent 7-dehydrocholesterol reductase inhibitors.
AB  - We prepared a number of N-phenethyltetrahydroisoquinolines structurally related
      to protoberberines. They were tested for activity against bacteria, fungi, and
      human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in
      yeasts and cholesterol in human cells. In the latter assay panel, several of the
      compounds were distinguished by a strong and selective inhibition of 7
      dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the
      conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol
      biosynthesis. In a whole-cell assay, the most active compound 5f showed a much
      stronger inhibition of overall cholesterol biosynthesis (IC(50) 2.3 nM) than BM
      15.766 (IC(50) 500 nM), presently the most selective known inhibitor of 7-DHCR.
      Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli
      Opitz syndrome (SLOS), the potent and selective inhibitors reported here will
      enable more detailed investigation of the pathogenesis of SLOS.

PMID- 22882120
TI  - A novel spider peptide toxin suppresses tumor growth through dual signaling
      pathways.
AB  - Spider venom is a large pharmacological repertoire containing many biologically
      active peptides, which may have a potent therapeutic implication. Here we
      investigated a peptide toxin, named lycosin-I, isolated from the venom of the
      spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting
      inhibitor cystine knot (ICK) motif, lycosin-I shows a linear amphipathic alpha
      helical conformation, common to alpha-helical host defense peptides. Lycosin-I
      displays strong ability to inhibit cancer cell growth in vitro and can
      effectively suppresses tumor growth in vivo. Mechanistically, it activates the
      mitochondrial death pathway to sensitize cancer cells for apoptosis, as well as
      up-regulates p27 to inhibit cell proliferation. Taken together, our results
      provide the first evidence that a spider toxin can effectively suppress
      tumorigenesis through activation of dual signaling pathways. In addition, lycosin
      I may be a useful structural lead for the development of novel anticancer drugs.

PMID- 22882121
TI  - Alcohol use and client-perpetrated sexual violence against female sex workers in
      China.
AB  - The global literature suggests that female sex workers (FSWs) experience high
      rates of sexual violence perpetrated by their clients, especially when FSWs are
      under the influence of alcohol. However, such data are limited in China. The
      current study is aimed to fill in the literature gap by examining the association
      between alcohol use by FSWs and client-perpetrated sexual violence against FSWs
      in China. A total of 1022 FSWs were recruited through community outreach in
      Guangxi, China. Female sex workers completed a self-administered survey on their
      demographic information, alcohol use, and sexual violence perpetrated by clients.
      Multivariable regression was employed to assess the relationship between alcohol
      use and client-perpetrated sexual violence among FSWs while controlling for
      possible confounders. Results indicated that alcohol use was positively
      associated with the experience of sexual violence in both bivariate and
      multivariable analyses. Women who were at a higher risk level of alcohol use were
      more likely to experience sexual violence perpetrated by clients even after
      controlling confounders (e.g., demographics and alcohol-serving practice). Given
      the association between alcohol use and client-perpetrated sexual violence,
      preventing or reducing alcohol use among FSWs could be an effective strategy to
      protect these women from sexual violence perpetrated by their clients.
      Alternatively, psychological counseling and other support should be available to
      these women so they can reduce their alcohol use as a maladaptive coping
      strategy. We call for culturally appropriate alcohol use reduction components,
      incorporated with sexual violence reduction strategies including adaptive coping
      skills training as well as empowerment, and targeting both FSWs and their
      clients.

PMID- 22882122
TI  - Pharmacokinetics and bioequivalence in the pig of two ivermectin feed
      formulations.
AB  - Two premix products containing the endectocide ivermectin were compared for
      pharmacokinetic profiles and bioequivalence in young pigs. Test and reference
      articles were administered to individual pigs in-feed at 12-h intervals for a
      total of 14 doses. Plasma concentration-time profiles were compared after
      provision of the final doses of medicated feed, by which time steady-state
      concentrations of ivermectin had been achieved. The pharmacokinetic variables
      monitored were peak concentration (Cmax ), area under the curve (AUC)0-last ,
      elimination half-life of the terminal phase (T1/2 lambdaz) and average steady
      state concentration (Css ), determined by noncompartmental analysis. Logarithmic
      transformation of the variables was carried out when appropriate. Analysis of
      data by the Classic Method yielded confidence intervals of 80.59-114.47 (for AUC0
      last ), 90.38-119.68 (for Cmax ) and 84.70-111.96 (for Css ). It was concluded
      that the two articles were bioequivalent for ivermectin.

PMID- 22882123
TI  - Childhood predictors of becoming a teenage mother among Finnish girls.
AB  - OBJECTIVE: To study predictive associations between psychosocial factors at age 8
      and becoming a mother under the age of 20. DESIGN: Prospective follow-up study.
      SETTING: Finland. POPULATION: 2867 girls born in 1981. METHODS: Information on
      family background and psychiatric symptoms was collected at age 8. The
      associations between these factors and becoming a teenage mother were analyzed
      using logistic regression analysis. MAIN OUTCOME MEASURES: Data on births by the
      age of 20 collected from the hospital discharge register. RESULTS: 128 girls
      (4.8%) had given birth at the age of 15-19 years. Childhood conduct problems and
      hyperactive problems, having young mother and family structure other than two
      biological parents had an independent association with becoming a teenage mother.
      CONCLUSIONS: Girls with externalizing type of problems in childhood have an
      increased risk of becoming teenage mothers. These problems may also complicate
      their motherhood.

PMID- 22882124
TI  - Helping individuals to understand synergistic risks: an assessment of message
      contents depicting mechanistic and probabilistic concepts.
AB  - Accumulating evidence shows that certain hazard combinations interact to present
      synergistic risks. However, little is known about the most effective ways of
      helping individuals to understand this complex risk concept. More specifically,
      there is an absence of empirical research that has assessed the relative efficacy
      of messages that explain either the causal mechanism and/or the probabilistic
      components of synergistic risks. In an experiment designed to address this issue,
      we presented participants with messages concerning the synergistic risk of
      developing esophageal cancer for individuals who consume both tobacco and
      alcohol. Relative to a control group, we compared the extent to which messages
      featuring content detailing the underlying biological mechanism, the
      probabilistic risk, or both improved understanding of the synergistic risk. Our
      results showed that messages containing details of both the mechanism and
      probabilistic information were most effective at enabling individuals to
      understand that the alcohol-tobacco combination presents a synergistic risk. In
      addition, large improvements in the accuracy of cancer frequency estimates were
      observed amongst individuals who received probabilistic information, and the
      highest relative increase in professed willingness to adopt precautionary
      behaviors was observed amongst individuals who received the mechanism information
      only. Importantly, these findings could be utilized in the development of a
      general model for the communication of synergistic risks. Furthermore, in
      contrast to previous findings, our study demonstrates that risk messages can be
      both effective and efficient in helping individuals to acquire a greater
      understanding of synergistic risks. Acquiring such knowledge could lead to
      significant improvements in risk-related decisions concerning combined hazards.

PMID- 22882125
TI  - Differential effect of three base modifications on DNA thermostability revealed
      by high resolution melting.
AB  - High resolution melting (HRM) can detect and quantify the presence of 5
      methylcytosine (5mC) in DNA samples, but the ability of HRM to diagnose other DNA
      modifications remains unexplored. The DNA bases N6-methyladenine and 5
      hydroxymethylcytosine occur across almost all phyla. While their function remains
      controversial, their presence perturbs DNA structure. Such modifications could
      affect gene regulation, chromatin condensation and DNA packaging. Here, we reveal
      that DNA containing N6-methyladenine or 5-hydroxymethylcytosine exhibits reduced
      thermal stability compared to cytosine-methylated DNA. These thermostability
      changes are sufficiently divergent to allow detection and quantification by HRM
      analysis. Thus, we report that HRM distinguishes between sequence-identical DNA
      differing only in the modification type of one base. This approach is also able
      to distinguish between two DNA fragments carrying both N6-methyladenine and 5
      methylcytosine but differing only in the distance separating the modified bases.
      This finding provides scope for the development of new methods to characterize
      DNA chemically and to allow for low cost screening of mutant populations of genes
      involved in base modification. More fundamentally, contrast between the
      thermostabilizing effects of 5mC on dsDNA compared with the destabilizing effects
      of N6-methyladenine (m6A) and 5-hydroxymethylcytosine (5hmC) raises the
      intriguing possibility of an antagonistic relationship between modification types
      with functional significance.

PMID- 22882126
TI  - The effect of an amphiphilic self-assembled lipid lamellar phase on the relief of
      dry skin.
AB  - Humectant and occlusive technologies have traditionally been used for the
      treatment of dry skin. Originally, non-lamellar-forming ingredients were used
      such as petrolatum but recent research has shown the advantage of using lamellar
      forming ingredients such as ceramides, pseudoceramides and phospholipids in the
      relief of dry skin. Nevertheless, the importance of using lipid-phase transition
      inducers, such as long-chain fatty acids, has not been studied clinically. The
      evaluation of a novel complex of lipophilic ingredients was of interest: cetyl
      alcohol, isostearyl isostearate, potassium cetyl phosphate, cetyl behenate and
      behenic acid. The combination of all these ingredients was shown to be more
      effective than any single component in water vapour transmission rate studies.
      This was thought to be owing to the formation of a unique structural organization
      of the lipids upon dry-down from an O/W emulsion as was examined by X-ray
      diffraction and optical microscopy. When evaluated clinically in a randomized
      double-blind and vehicle-controlled moisturization efficacy trial, this novel
      blend of ingredients was shown to not only improve the visible signs of skin
      dryness to a significantly greater extent than a comparable mineral oil
      containing vehicle but also then maintain a better skin condition during the
      regression no-treatment phase of the study. This combination of ingredients
      offers a new technology option for the treatment of dry skin.

PMID- 22882127
TI  - Rectal lymphoma in 11 dogs: a retrospective study.
AB  - OBJECTIVES: To retrospectively evaluate the clinical behaviour and
      immunophenotype of lymphoma of the rectum in dogs. METHODS: Eleven dogs diagnosed
      with lymphoma of the rectum on histopathology were retrospectively reviewed.
      Immunohistochemistry with CD3 and CD79a antibodies was performed at diagnosis or
      retrospectively. RESULTS: Treatment protocol varied with six dogs undergoing
      surgery and adjuvant chemotherapy, two received chemotherapy after only
      incisional biopsy, one had surgical resection only, one was treated
      symptomatically and one dog was not treated. Chemotherapy treatment consisted of
      either a -low-dose COP (cyclophosphamide - prednisolone - vincristine) protocol
      (four dogs) or a six-week CHOP-based (cyclophosphamide - vincristine - 
      prednisolone - anthracycline) protocol (four dogs). Dogs that received
      chemotherapy lived significantly longer than dogs that did not receive
      chemotherapy (2352 versus 70 days). Median survival time was not reached, and
      there was an overall mean survival time of 1697 days. Immunohistochemistry was
      performed in 10 of 11 samples, and was consistent with B-cell -lymphoma in all
      cases. CLINICAL SIGNIFICANCE: Canine lymphoma of the rectum is associated with a
      favourable prognosis. Immunohistochemical evaluation of these lesions was
      consistent with B-cell lymphoma in all cases in which it was examined.

PMID- 22882128
TI  - Exon 8 amplification of epidermal growth factor receptor (EGFR) in invasive
      breast carcinomas.
AB  - AIMS: The rate of EGFR amplification in breast cancer ranges between 0% and 15%.
      Recent studies have focused on the amplification status of cytosine-adenine (CA)
      repeats in intron 1 of the gene and correlated it with increased EGFR protein.
      The aim of this study was to investigate, for the first time, the significance of
      coding exon 8 amplification of EGFR in invasive breast cancer. METHODS AND
      RESULTS: We investigated, by means of real-time polymerase chain reaction (PCR),
      the amplification status of exon 8 of the EGFR gene in 148 paraffin-embedded
      tissue sections, 115 with invasive breast carcinoma and 33 controls.
      Immunohistochemistry was utilized to detect EGFR and human epidermal growth
      factor receptor 2 (HER2) expression. Univariate and multivariate statistical
      analyses were performed for the evaluation of our results. EGFR amplification was
      observed in 7.8% of the patients, and EGFR was immunodetected in 9.6%. EGFR
      amplification was correlated positively with EGFR expression (P < 0.0001), HER2
      expression (P = 0.023), coexpression of EGFR/HER2 (P < 0.0001) and nuclear grade
      (P = 0.047), and inversely with ER protein expression (P = .047). CONCLUSION: It
      appears that amplification of the coding sequence exon 8 exhibits similar
      biological behaviour to amplification of the regulatory sequence in intron 1,
      leading to elevated levels of EGFR protein.

PMID- 22882129
TI  - Dermal hypersensitivity reaction: a PCR-confirmed pattern of herpetic dermatitis.
AB  - BACKGROUND: Herpetic dermatitis due to herpes simplex virus (HSV) and varicella
      zoster virus (VZV) can present with similar clinical and histopathologic
      features. Further confounding matters, viral cytopathic changes are not always
      observed in biopsy specimens. Therefore, use of polymerase chain reaction (PCR)
      analysis can play an integral role in the definitive diagnosis of herpetic
      dermatitis and in the distinction of HSV-1/HSV-2 from VZV. METHODS: Forty
      patients with skin biopsies (2004-2011) had PCR analysis performed to detect HSV
      1/2 or VZV. Patient demographics, clinical impression and histopathologic
      characteristics were reviewed and correlated with PCR findings. RESULTS: Overall,
      there was complete correlation between clinical impression, histopathology and
      PCR results in 21 of 40 cases. In 19 cases, clinical impression and
      histopathology were discrepant and in 15 of these cases PCR confirmed HSV or VZV
      infection. We also describe 3 cases of herpetic dermatitis without viral change
      that histopathologically demonstrate the pattern of a dermal hypersensitivity
      reaction. CONCLUSIONS: The results of this study suggest that routine use of PCR
      for definitive diagnosis of herpetic dermatitis should be considered when there
      is a clinical suspicion of herpes virus infection, even when there is a lack of
      specific histopathologic findings. Additionally, a dermal hypersensitivity
      reaction should be recognized as one histopathologic manifestation of herpes
      incognito.

PMID- 22882130
TI  - Effects of intentional delivery on maternal and neonatal outcomes in pregnancies
      with preterm prelabour rupture of membranes between 28 and 34 weeks of gestation:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effects of intentional delivery (ID) over expectant
      management (EM) in pregnancies complicated by preterm prelabour rupture of
      membranes (PPROM) between 28 and 34 weeks of gestation on maternal and neonatal
      outcomes. METHODS: We searched Ovid MEDLINE, EMBASE, CINAHL, CENTRAL and Science
      Citation Index; contacted experts and checked reference lists of relevant
      studies. Studies were included if they were randomized controlled trials in all
      languages. RESULTS: Five randomized trials were included and 488 subjects were
      analyzed. Overall, the results showed significant heterogeneity. Maternal
      infection as well as respiratory distress syndrome (RDS) & neonatal sepsis (NS)
      were not different between the two groups. Neonatal death, however, was
      significantly higher (risk ratio: 5.81; 95% CI: 1.35-25.08; p = 0.03) in the ID
      group after excluding studies that gave antenatal steroids. Incidence of cesarean
      section was significantly higher in the intentional delivery group, as well (risk
      ratio: 1.35; 95% CI: 1.02-1.80; p = 0.03). CONCLUSION: Based on the available
      evidence, ID in pregnancies complicated with PPROM between 28 and 34 weeks
      carries some maternal and neonatal risks with no added benefits. Thus, this
      treatment should not be considered as an option for women with PPROM before 34
      weeks of gestation in the absence of other indications for early delivery.

PMID- 22882131
TI  - Editorial comment to adrenal myelolipoma associated with hyperandrogenemia.

PMID- 22882133
TI  - Can exercise training rescue the adverse cardiometabolic effects of low birth
      weight and prematurity?
AB  - Being born preterm and/or small for gestational age are well-established risk
      factors for cardiometabolic disease in adulthood. Physical activity has the
      potential to mitigate against the detrimental cardiometabolic effects of low
      birth weight from two perspectives: (i) maternal exercise prior to and during
      pregnancy; and (ii) exercise during childhood or adulthood for those born small
      or prematurely. Evidence from epidemiological birth cohort studies suggests that
      the effects of moderate-intensity physical activity during pregnancy on mean
      birth weight are small, but reduce the risk of either high or low birth weight
      infants. In contrast, vigorous and/or high-intensity exercise during pregnancy
      has been associated with reduced birth weight. In childhood and adolescence,
      exercise ability is compromised in extremely low birth weight individuals (< 1000
      g), but only marginally reduced in those of very low to low birth weight (1000
      2500 g). Epidemiological studies show that the association between birth weight
      and metabolic disease is lost in physically fit individuals and, consistently,
      that the association between low birth weight and metabolic syndrome is
      accentuated in unfit individuals. Physical activity intervention studies indicate
      that most cardiometabolic risk factors respond to exercise in a protective
      manner, independent of birth weight. The mechanisms by which exercise may protect
      low birth weight individuals include restoration of muscle mass, reduced
      adiposity and enhanced beta-cell mass and function, as well as effects on both
      aerobic and anaerobic muscle metabolism, including substrate utilization and
      mitochondrial function. Vascular and cardiac adaptations are also likely
      important, but are less well studied.

PMID- 22882132
TI  - Low-shear red blood cell oxygen transport effectiveness is adversely affected by
      transfusion and further worsened by deoxygenation in sickle cell disease patients
      on chronic transfusion therapy.
AB  - BACKGROUND: Simple chronic transfusion therapy (CTT) is a mainstay for stroke
      prophylaxis in sickle cell anemia, but its effects on hemodynamics are poorly
      characterized. Transfusion improves oxygen-carrying capacity, reducing demands
      for high cardiac output. While transfusion decreases factors associated with
      vasoocclusion, including percent hemoglobin (Hb)S, reticulocyte count, and
      circulating cell-free Hb, it increases blood viscosity, which reduces
      microvascular flow. The hematocrit-to-viscosity ratio (HVR) is an index of red
      blood cell oxygen transport effectiveness that varies with shear stress and
      balances the benefits of improved oxygen capacity to viscosity-mediated
      impairment of microvascular flow. We hypothesized that transfusion would improve
      HVR at high shear despite increased blood viscosity, but would decrease HVR at
      low shear. STUDY DESIGN AND METHODS: To test this hypothesis, we examined
      oxygenated and deoxygenated blood samples from 15 sickle cell patients on CTT
      immediately before transfusion and again 12 to 120 hours after transfusion.
      RESULTS: Comparable changes in Hb, hematocrit (Hct), reticulocyte count, and HbS
      with transfusion were observed in all subjects. Viscosity, Hct, and high-shear
      HVR increased with transfusion while low-shear HVR decreased significantly.
      CONCLUSION: Decreased low-shear HVR suggests impaired oxygen transport to low
      flow regions and may explain why some complications of sickle cell anemia are
      ameliorated by CTT and others may be made worse.

PMID- 22882134
TI  - Teratogenesis in repeated pregnancies in antiepileptic drug-treated women.
AB  - PURPOSE: Considerable information is now available concerning the risk of
      teratogenesis in the individual pregnancy exposed to antiepileptic drugs (AEDs).
      However, there is comparatively little information available concerning the risk
      in the subsequent pregnancies of women who continue to take the AED associated
      with a fetal malformation in a previous pregnancy. This article addresses this
      matter. METHODS: Analysis of data concerning fetal abnormalities in 1,243 women
      who had 2,637 pregnancies between mid-1999 and 2010 recorded in the Australian
      Register of Antiepileptic Drugs in Pregnancy. Of the 2,637 pregnancies, 1,114 had
      been completed before initial enrolment in the Register. KEY FINDINGS: Women
      taking any AED who had given birth to a malformed baby in their first enrolled
      pregnancy and who continue taking the same drug were at increased risk of having
      a malformed offspring in their next pregnancy (35.7% vs. 3.1%; odds ratio [OR]
      17.6; 95% confidence interval [95% CI] 4.5-68.7). Among these women, those taking
      valproate (VPA) were more likely to have malformed fetuses in their next
      pregnancies than those who had taken VPA without fetal abnormalities (57.2% vs.
      7.0%, OR 17.8; 95% CI 2.7, 119.1). There were similar although not statistically
      significant trends in those who had taken AEDs other than VPA. Similar, although
      again not statistically significant, trends were found, when considering the
      pairings of the most recent preenrollment pregnancy and the following one. If a
      woman had two or more pregnancies that resulted in AED-associated fetal
      malformation, the types of malformation were often different. SIGNIFICANCE: Women
      whose last pregnancy resulted in a fetal malformation have a substantially
      increased risk of having further malformed fetuses if they become pregnant again
      while taking the same AED, particularly VPA. This suggests that maternal factors,
      perhaps genomic, predispose to at least VPA-associated malformations. This
      knowledge, together with information about the outcome of any previous pregnancy,
      should help in advising women with AED-treated epilepsy who plan further
      pregnancies.

PMID- 22882135
TI  - Construction of benzosiloles, six- and eight-membered silacyclic skeletons, via a
      Pd-catalyzed intramolecular Mizoroki-Heck reaction of vinylsilanes.
AB  - A variety of silacycles including benzosiloles, six- and eight-membered
      silacyclic skeletons, were efficiently synthesized via a Pd-catalyzed
      intramolecular Mizoroki-Heck reaction of vinylsilanes.

PMID- 22882136
TI  - Phacoemulsification considerations in nonhuman primates.
AB  - PURPOSE: To describe the pre-surgical, surgical, and post-surgical considerations
      for phacoemulsification in non-human primates. METHODS: Records of non-human
      primates that underwent phacoemulsification by the Ophthalmology Services of FHCV
      UAB and HCV-UM, between 2003 and 2009 were reviewed. RESULTS: Five primates were
      represented: one gorilla, one chimpanzee, one pygmy marmoset, one orangutan, and
      one chacma baboon. Three were males and two females, of a median age of 16.8
      years. Four primates presented bilateral cataracts and one unilateral (n = 9
      eyes). Cataracts were immature in two eyes, mature in four and hypermature in 3.
      One-handed phacoemulsification was used in seven eyes and a two-handed technique
      in 2. Intraocular lenses (IOLs), with optic powers between +19.0 and +21.5D, were
      implanted in the four large-sized primates. All the primates were more active and
      social after the surgery. CONCLUSION: Phacoemulsification in non-human primates
      is highly successful and associated with an overall good visual outcome.
      Nevertheless, specific considerations should be applied in these species.

PMID- 22882137
TI  - Facilitation of quadriceps activation is impaired following eccentric exercise.
AB  - Contracting the knee flexor muscles immediately before a maximum voluntary
      contraction (MVC) of knee extension increases the maximal force that the extensor
      muscles can exert. It is hypothesized that this phenomenon can be impaired by
      muscle fiber damage following eccentric exercise [delayed onset muscle soreness
      (DOMS)]. This study investigates the effect of eccentric exercise and DOMS on
      knee extension MVC immediately following a reciprocal-resisted knee flexion
      contraction. Electromyography (EMG) was recorded from the knee extensors and
      flexors of 12 healthy men during knee extension MVCs performed in a reciprocal
      (maximal knee extension preceded by resisted knee flexion), and nonreciprocal
      condition (preceded by relaxation of the knee flexors). At baseline, knee
      extension MVC force was greater during the reciprocal condition (P < 0.001),
      whereas immediately after, 24 and 48 h after eccentric exercise, the MVC force
      was not different between conditions. Similarly, at baseline, the EMG amplitude
      of the quadriceps during the MVC was larger for the reciprocal condition (P <
      0.001). However, immediately after, 24 and 48 h postexercise the EMG amplitude
      was similar between conditions. In conclusion, eccentric exercise abolished the
      facilitation of force production for the knee extensors, which normally occurs
      when maximum knee extension is preceded by activation of the knee flexors.

PMID- 22882139
TI  - Nerve growth factor and the physiology of pain: lessons from congenital
      insensitivity to pain with anhidrosis.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive
      genetic disorder characterized by insensitivity to pain, anhidrosis (the
      inability to sweat) and mental retardation. Nerve growth factor (NGF) is a well
      known neurotrophic factor essential for the survival and maintenance of NGF
      dependent neurons, including primary afferent neurons with thin fibers and
      sympathetic postganglionic neurons, during development. NGF is also considered to
      be an inflammatory mediator associated with pain, itch and inflammation in
      adults. CIPA results from loss-of-function mutations in the NTRK1 gene-encoding
      TrkA (tropomyosin-related kinase A), a receptor tyrosine kinase for NGF. Defects
      in NGF-TrkA signal transduction lead to the failure of survival of various NGF
      dependent neurons. As a result, patients with CIPA lack NGF-dependent neurons.
      Recent studies have revealed that mutations in the NGFB gene-encoding NGF protein
      also cause congenital insensitivity to pain. Using the pathophysiology of CIPA as
      a foundation, this review investigates the ways in which NGF-dependent neurons
      contribute to interoception, homeostasis and emotional responses and, together
      with the brain, immune and endocrine systems, play crucial roles in pain, itch
      and inflammation. The NGF-TrkA system is essential for the establishment of
      neural networks for interoception, homeostasis and emotional responses. These
      networks mediate reciprocal communication between the brain and the body in
      humans.

PMID- 22882140
TI  - Dye dynamics in three-color FRET samples.
AB  - Time-resolved emission data (fluorescence decay and fluorescence depolarization)
      of two three-color Forster resonance energy transfer (tc-FRET) systems consisting
      of a carbostyril donor (D), a ruthenium complex (Ru) as relay dye, and a Cy5
      derivative (Cy) or, optionally, an anthraquinone quencher (Q) were carefully
      analyzed using advanced distribution analysis models. Thereby, it is possible to
      get information on the flexibility and mobility of the chromophores which are
      bound to double stranded (ds) DNA. Especially the distance distribution based on
      the analysis of the fluorescence depolarization is an attractive approach to
      complement data of fluorescence decay time analysis. The distance distributions
      extracted from the experimental data were in excellent agreement with those
      determined from accessible volume (AV) simulations. Moreover, the study showed
      that for tc-FRET systems the combination of dyes emitting on different time
      scales (e.g., nanoseconds vs microseconds) is highly beneficial in the
      distribution analysis of time-resolved luminescence data in cases where
      macromolecules such as DNA are involved. Here, the short lifetimes can yield
      information on the rotation of the dye molecule itself and the long lifetime can
      give insight in the overall dynamics of the macromolecule.

PMID- 22882138
TI  - The energy value of biodiesel glycerine products fed to broilers at different
      ages.
AB  - The objective of this study was to determine the apparent metabolisable energy
      corrected for nitrogen balance (AMEn) of some products containing glycerine from
      soybean oil (GOIL), a mixture of frying oil and lard (GMIX) and a semi-purified
      process (GSP) in broilers of different ages (10, 20, 30 and 40 days post
      hatching), using two methodologies. In trial 1, the basal diets were replaced
      with 100 g/kg of each studied glycerine product and the diets were supplied ad
      libitum. Three hundred broilers were used in five replicates, with five, four,
      three and three animals per cage in each age group, respectively. The AMEn was
      calculated for each experimental unit. In trial 2, dietary treatments included
      the addition of glycerine at 0, 40, 80 or 120 g/kg for each crude glycerine
      product, with 900 broilers in six replicates, using the same number of animals
      per cage as described in trial 1. Depending on the experimental unit, the feeding
      was restricted in 88%, 92%, 96% and 100% of estimated intake according to the
      Cobb guide. The AMEn was determined using linear regression between the feed
      intake and the AMEn of each diet. In both trials, the total excreta collection
      method was used. Because of the chemical composition, GMIX was not considered
      crude glycerine. The mean AMEn values of the products were 20.55 MJ/kg, 15.80
      MJ/kg and 15.05 MJ/kg for GMIX, GSP and GOIL, respectively. There was a linear
      decrease (p < 0.01) in the AMEn values with the increasing age of the broilers.
      Numerically, it was observed that the AMEn values decreased until 28-30 day post
      hatching and then remained constant until the finishing phase. It is concluded
      that products containing glycerine can be used as an energy source for broilers,
      but that AMEn values can vary according to age. Younger broilers have a higher
      capacity of energy utilisation from these feedstuffs. 

PMID- 22882141
TI  - Prevalence of hydrogen cyanide and carboxyhaemoglobin in victims of smoke
      inhalation during enclosed-space fires: a combined toxicological risk.
AB  - BACKGROUND: Hydrogen cyanide (HCN) is one of the most toxic components of fire
      smoke, but insufficient attention is paid to its potential role as a cause of
      injury or death in victims (alive or dead) of enclosed-space fires. OBJECTIVE: To
      analyse the prevalence of toxic HCN exposure in fire victims and factors that may
      influence its toxicity, particularly the co-presence of carbon monoxide (CO) and
      ethanol. MATERIALS AND METHODS: Blood samples from fire victims and persons
      rescued from fires were analysed. RESULTS: A positive result for HCN (mean
      concentration 16.83 mg/l) was detected in blood samples from 169 of 285 fire
      related deaths (59%). Ethanol was present in 91 (65%) of 139 samples with
      coincident presence of HCN and carboxyhaemoglobin (COHb). HCN (mean 4.0 mg/l) was
      also detected in 20 of 40 (50%) fire survivors. DISCUSSION: The high prevalence
      of coincident CO and HCN in enclosed-space, fire-related deaths should alert
      clinicians to suspect toxic HCN exposure in all persons rescued from fire with
      signs and symptoms of respiratory distress. CONCLUSIONS: Medical procedures in
      persons rescued from enclosed-space fires, especially in the pre-hospital
      setting, should be augmented to cover the possibility of toxic HCN exposure,
      particularly in individuals who do not respond to standard supportive therapy.
      Likewise, post-mortem investigations should routinely include assays for HCN when
      determining probable cause of death.

PMID- 22882142
TI  - Wicked problems: policy contradictions in publicly financed dental care.
AB  - OBJECTIVES: To review two policy issues that define publicly financed dental care
      as a "wicked policy problem." METHODS: Historical review. RESULTS: By
      demonstrating how governments have shifted their funding focus from direct
      delivery care, to public third-party financing arrangements in private dental
      offices, and by their willingness to fund composite restorations in public fee
      schedules, it is clear that the logic and sustainability of public programming
      needs reconsideration. CONCLUSIONS: The current contradictions in public dental
      care programs speak to the need for policy makers to reassess their goals, and
      ask whether decisions are based more on political necessity than on a logical
      evidence-informed approach to the delivery of publicly financed dental care.

PMID- 22882143
TI  - The auxiliary protein complex SaePQ activates the phosphatase activity of sensor
      kinase SaeS in the SaeRS two-component system of Staphylococcus aureus.
AB  - In bacterial two-component regulatory systems (TCSs), dephosphorylation of
      phosphorylated response regulators is essential for resetting the activated
      systems to the pre-activation state. However, in the SaeRS TCS, a major virulence
      TCS of Staphylococcus aureus, the mechanism for dephosphorylation of the response
      regulator SaeR has not been identified. Here we report that two auxiliary
      proteins from the sae operon, SaeP and SaeQ, form a protein complex with the
      sensor kinase SaeS and activate the sensor kinase's phosphatase activity.
      Efficient activation of the phosphatase activity required the presence of both
      SaeP and SaeQ. When SaeP and SaeQ were ectopically expressed, the expression of
      coagulase, a sae target with low affinity for phosphorylated SaeR, was greatly
      reduced, while the expression of alpha-haemolysin, a sae target with high
      affinity for phosphorylated SaeR, was not, demonstrating a differential effect of
      SaePQ on sae target gene expression. When expression of SaePQ was abolished, most
      sae target genes were induced at an elevated level. Since the expression of SaeP
      and SaeQ is induced by the SaeRS TCS, these results suggest that the SaeRS TCS
      returns to the pre-activation state by a negative feedback mechanism.

PMID- 22882145
TI  - Simultaneous quantification of tumor uptake for targeted and nontargeted
      liposomes and their encapsulated contents by ICPMS.
AB  - Liposomes are intensively being developed for biomedical applications including
      drug and gene delivery. However, targeted liposomal delivery in cancer treatment
      is a very complicated multistep process. Unfavorable liposome biodistribution
      upon intravenous administration and membrane destabilization in blood circulation
      could result in only a very small fraction of cargo reaching the tumors. It would
      therefore be desirable to develop new quantitative strategies to track liposomal
      delivery systems to improve the therapeutic index and decrease systemic toxicity.
      Here, we developed a simple and nonradiative method to quantify the tumor uptake
      of targeted and nontargeted control liposomes as well as their encapsulated
      contents simultaneously. Specifically, four different chelated lanthanide metals
      were encapsulated or surface-conjugated onto tumor-targeted and nontargeted
      liposomes, respectively. The two liposome formulations were then injected into
      tumor-bearing mice simultaneously, and their tumor delivery was determined
      quantitatively via inductively coupled plasma mass spectroscopy (ICPMS), allowing
      for direct comparisons. Tumor uptake of the liposomes themselves and their
      encapsulated contents was consistent with targeted and nontargeted liposome
      formulations that were injected individually.

PMID- 22882144
TI  - Performance of young adult cannabis users on neurocognitive measures of impulsive
      behavior and their relationship to symptoms of cannabis use disorders.
AB  - Recent studies suggest that abstinent cannabis users show deficits on
      neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and
      less is known on the performance of non-treatment-seeking, young adult cannabis
      users. Importantly, relationships between performance on measures of impulsive
      behavior and symptoms of cannabis addiction remain relatively unexplored. We
      compared young adult current cannabis users (CU, n = 65) and nonusing controls
      (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on
      a measure of episodic memory commonly impacted by cannabis use. The CU group
      performed more poorly than the NU group on the Hopkins Verbal Learning Test
      Revised Total Immediate Recall and Delayed Recall. No significant differences
      were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task,
      IGT; Go-Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We
      examined relationships between neurocognitive performance and symptoms of
      cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental
      Disorders-Fourth Edition, DSM-IV CUD) among the CU group, which revealed that
      poorer IGT performance was associated with more symptoms of DSM-IV CUD. Our
      results show poorer memory performance among young adult cannabis users than
      among healthy controls, but no differences on measures of impulsive behavior.
      However, performance on a specific type of impulsive behavior (i.e., poorer
      decision making) was associated with more cannabis use disorder symptoms. These
      results provide preliminary evidence to suggest that decision-making deficits may
      be more strongly associated with problems experienced from cannabis use, rather
      than solely being a consequence of cannabis use, per se.

PMID- 22882146
TI  - Cross-cultural validity of the Individualised Care Scale - a Rasch model
      analysis.
AB  - AIMS AND OBJECTIVES: The aim of this study was to investigate, using Rasch model
      analysis, the measurement invariance of the item ratings of the Individualised
      Care Scale. BACKGROUND: Evidence of reliability is needed in cross-cultural
      comparative studies. To be used in different cultures and languages, the items
      must function the same way. DESIGN: A methodological and comparative design.
      METHODS: Secondary analysis of data, gathered in 2005-2006 from a cross-cultural
      survey using the Individualised Care Scale from Finnish, Greek, Swedish and
      English predischarge hospitalised orthopaedic and trauma patients (n = 1093), was
      used. The Rasch model, which produces calibrations (item locations and rank) and
      item fit statistics, was computed using the Winstep program. RESULTS: The rank of
      average Individualised Care Scale item calibrations (-2.26-1.52) followed a
      generally similar trend (Infit <= 1.3), but slight differences in the item rank
      by country were found and some item misfit was identified within the same items.
      There was some variation in the order and location of some Individualised Care
      Scale items for individual countries, but the overall pattern of item calibration
      was generally corresponding. CONCLUSIONS: The Rasch model provided information
      about the appropriateness, sensitivity and item function in different cultures
      providing more in-depth information about the psychometric properties of the
      Individualised Care Scale instrument. Comparison of the four versions of the
      Individualised Care Scale - patient revealed general correspondence in the item
      calibration patterns although slight differences in the rank order of the items
      were found. Some items showed also a slight misfit. Based on these results, the
      phrasing and targeting of some items should be considered. RELEVANCE TO CLINICAL
      PRACTICE: The Individualised Care Scale - Patient version can be used in cross
      cultural studies for the measurement of patients' perceptions of individualised
      care. Information obtained with the use of the Individualised Care Scale in
      clinical nursing practice is important, and valid measures are needed in
      evaluating patients' assessment of individualised care, one indicator of care
      quality.

PMID- 22882147
TI  - Impairment of mature dendritic cells derived from X-irradiated human monocytes
      depends on the type of maturation stimulus used.
AB  - Dendritic cells play an essential role in the immune system. We have previously
      reported that X-irradiated monocytes, precursors of dendritic cells, can
      differentiate into dendritic cells and then mature in terms of surface antigen
      expression after tumor necrosis factor-alpha stimulation, but show reduced
      functionality. Dendritic cells can mature in response to various types of
      maturation stimuli. Therefore, this study investigated whether dendritic cells
      from monocytes exposed to ionizing radiation can adequately respond to pathogen
      derived components and proinflammatory cytokines. Human monocytes separated from
      buffy coats were exposed to X rays, and were then differentiated into immature
      dendritic cells. Immature dendritic cells were stimulated by lipopolysaccharide
      (LPS) or proinflammatory cytokine mixture. The dendritic cells from nonirradiated
      and X-irradiated monocytes showed maturation after LPS and proinflammatory
      cytokine mixture stimulation as confirmed by findings of surface antigen
      expression. Upon LPS stimulation, however, the expression levels of CD80 and CD83
      on dendritic cells from X-irradiated monocytes were lower than those of dendritic
      cells from nonirradiated monocytes. Such reductions were not observed upon
      proinflammatory cytokine mixture stimulation. Similarly, an impairment of matrix
      metalloproteinase-9 and cytokine production was observed in LPS-stimulated
      dendritic cells from X-irradiated monocytes, whereas these impairments were not
      observed upon proinflammatory cytokine mixture stimulation. The ability of
      dendritic cells to stimulate T cells was lower in the irradiated group compared
      with the nonirradiated group despite the type of maturation stimulus. Thus, the
      present study suggests that the influence of X irradiation on the maturation of
      dendritic cells depends on the type of maturation stimulus used and that X
      irradiation impairs the response of dendritic cells to LPS.

PMID- 22882149
TI  - Vision and IT displays: a whole new visual world.

PMID- 22882148
TI  - S100P immunostaining identifies a subset of peripheral-type intrahepatic
      cholangiocarcinomas with morphological and molecular features similar to those of
      perihilar and extrahepatic cholangiocarcinomas.
AB  - AIMS: S100P is a calcium-binding protein that is frequently expressed in
      pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study
      was to investigate the pathological significance of the expression of S100P in
      peripheral intrahepatic cholangiocarcinoma (ICC). METHODS AND RESULTS:
      Immunohistochemical staining was used to investigate S100P expression in 112
      cases of peripheral ICC. The results were compared with those for perihilar and
      extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC
      were more likely to have elevated serum levels of carcinoembryonic antigen (CEA)
      and CA19-9 than those with S100P-negative peripheral ICCs. All cases of
      peripheral ICC associated with intrahepatic lithiasis and all cases with
      intraductal/periductal growth patterns were positive for S100P. S100P-positive
      peripheral ICCs were highly associated with 'bile duct' morphology rather than
      cholangiolar differentiation. Nearly all cases of perihilar and extrahepatic
      cholangiocarcinoma were positive for S100P. Similarly to perihilar and
      extrahepatic cholangiocarcinomas, S100P-positive peripheral ICCs showed more
      frequent expression of CEA and MUC2, and were more likely to be N-cadherin
      negative, than S100P-negative cases. Notably, K-RAS mutations were only detected
      in S100P-positive peripheral ICCs, with a frequency similar to that in perihilar
      and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC
      were more likely to have poor prognoses than those with S100P-negative tumours.
      CONCLUSIONS: S100P immunostaining identifies a subset of peripheral ICC that
      probably originates from larger bile ducts. This subset of peripheral ICCs shares
      common morphological and molecular features with perihilar and extrahepatic
      cholangiocarcinomas.

PMID- 22882150
TI  - Dynamic accommodative response to different visual stimuli (2D vs 3D) while
      watching television and while playing Nintendo 3DS console.
AB  - PURPOSE: The aim of the present study was to compare the accommodative response
      to the same visual content presented in two dimensions (2D) and stereoscopically
      in three dimensions (3D) while participants were either watching a television
      (TV) or Nintendo 3DS console. METHODS: Twenty-two university students, with a
      mean age of 20.3 +/- 2.0 years (mean +/- S.D.), were recruited to participate in
      the TV experiment and fifteen, with a mean age of 20.1 +/- 1.5 years took part in
      the Nintendo 3DS console study. The accommodative response was measured using a
      Grand Seiko WAM 5500 autorefractor. In the TV experiment, three conditions were
      used initially: the film was viewed in 2D mode (TV2D without glasses), the same
      sequence was watched in 2D whilst shutter-glasses were worn (TV2D with glasses)
      and the sequence was viewed in 3D mode (TV3D). Measurements were taken for 5 min
      in each condition, and these sections were sub-divided into ten 30-s segments to
      examine changes within the film. In addition, the accommodative response to three
      points of different disparity of one 3D frame was assessed for 30 s. In the
      Nintendo experiment, two conditions were employed - 2D viewing and stereoscopic
      3D viewing. RESULTS: In the TV experiment no statistically significant
      differences were found between the accommodative response with TV2D without
      glasses (-0.38 +/- 0.32D, mean +/- S.D.) and TV3D (-0.37 +/- 0.34D). Also, no
      differences were found between the various segments of the film, or between the
      accommodative response to different points of one frame (p > 0.05). A significant
      difference (p = 0.015) was found, however, between the TV2D with (-0.32 +/-
      0.32D) and without glasses (-0.38 +/- 0.32D). In the Nintendo experiment the
      accommodative responses obtained in modes 2D (-2.57 +/- 0.30D) and 3D (-2.49 +/-
      0.28D) were significantly different (paired t-test p = 0.03). CONCLUSIONS: The
      need to use shutter-glasses may affect the accommodative response during the
      viewing of displays, and the accommodative response when playing Nintendo 3DS in
      3D mode is lower than when it is viewed in 2D.

PMID- 22882151
TI  - Eye movement analysis of reading from computer displays, eReaders and printed
      books.
AB  - PURPOSE: To compare eye movements during silent reading of three eBooks and a
      printed book. The three different eReading tools were a desktop PC, iPad tablet
      and Kindle eReader. METHODS: Video-oculographic technology was used for recording
      eye movements. In the case of reading from the computer display the recordings
      were made by a video camera placed below the computer screen, whereas for reading
      from the iPad tablet, eReader and printed book the recording system was worn by
      the subject and had two cameras: one for recording the movement of the eyes and
      the other for recording the scene in front of the subject. RESULTS: Data analysis
      provided quantitative information in terms of number of fixations, their
      duration, and the direction of the movement, the latter to distinguish between
      fixations and regressions. Mean fixation duration was different only in reading
      from the computer display, and was similar for the Tablet, eReader and printed
      book. The percentage of regressions with respect to the total amount of fixations
      was comparable for eReading tools and the printed book. CONCLUSIONS: The analysis
      of eye movements during reading an eBook from different eReading tools suggests
      that subjects' reading behaviour is similar to reading from a printed book.

PMID- 22882152
TI  - Agreement analysis: further statistical insights.

PMID- 22882154
TI  - Intravenous immunoglobulin to treat neonatal alloimmune haemolytic disease.
AB  - OBJECTIVE: To compare the efficacy of intravenous immunoglobulin (IVIg) and
      exchange transfusion (EXT) on rhesus haemolytic disease of the newborn (Rh-HDN)
      and evaluate treatment-related side effects. METHODS: Retrospective chart review
      of two cohorts of newborns with Rh-HDN, treated with (Group 2) or without (Group
      1) IVIg. Length of phototherapy, number of EXT, IVIg infusions, intrauterine and
      top-up red blood cells transfusions, need and permanence of umbilical venous
      catheter, and length of hospital stay, as well as treatment-related adverse
      events, were evaluated. RESULTS: Charts of 88 newborns were reviewed (34 in Group
      1, 54 in Group 2). Infants in Group 2 received a significantly lower number of
      EXT, had a lower risk of neurological impairment and needed an umbilical venous
      catheter for shorter, but required longer phototherapy, longer length of hospital
      stay, and more top-up transfusions. EXT was associated with a high number of
      adverse events. Two newborns treated with IVIg developed necrotizing
      enterocolitis (NEC). CONCLUSIONS: IVIg appear as an effective alternative to EXT,
      reducing the risk of neurological impairment and complications related to EXT.
      However, side effects of IVIg treatment (higher need of top-up transfusions and
      longer hospital stay) should be taken into account and the risk of NEC should be
      carefully monitored during treatment.

PMID- 22882155
TI  - Trigger finger, tendinosis, and intratendinous gene expression.
AB  - The pathogenesis of trigger finger has generally been ascribed to primary changes
      in the first annular ligament. In contrast, we recently found histological
      changes in the tendons, similar to the findings in Achilles tendinosis or
      tendinopathy. We therefore hypothesized that trigger finger tendons would show
      differences in gene expression in comparison to normal tendons in a pattern
      similar to what is published for Achilles tendinosis. We performed quantitative
      real-time polymerase chain reaction on biopsies from finger flexor tendons, 13
      trigger fingers and 13 apparently healthy control tendons, to assess the
      expression of 10 genes which have been described to be differently expressed in
      tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3,
      aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen
      types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP
      3 were down-regulated. These changes were statistically significant and have been
      previously described for Achilles tendinosis. The remaining four genes were not
      significantly altered. The changes in gene expression support the hypothesis that
      trigger finger is a form of tendinosis. Because trigger finger is a common
      condition, often treated surgically, it could provide opportunities for clinical
      research on tendinosis.

PMID- 22882156
TI  - Pediatric apheresis with a novel apheresis device with electronic interface
      control.
AB  - BACKGROUND: Cancer in children, and specifically cancer requiring autologous stem
      cell transplantation, is rare. As a consequence, though, experience with
      pediatric stem cell apheresis collections is limited. Challenges of apheresis in
      small children (<20 kg) include small total blood volume, issues with venous
      access, concerns about tolerable anticoagulant doses, and limitations in product
      volumes that can safely be collected. STUDY DESIGN AND METHODS: This article
      presents a small series of autologous "stem cell" apheresis procedures in infants
      and toddlers weighing between 5.5 and 20 kg, the first ones performed with a
      novel leukapheresis device (Spectra Optia MNC v.3.0, Terumo BCT) to be reported.
      Some features of the system are described that can be used to achieve favorable
      apheresis outcomes in small children. RESULTS: Apheresis procedures were
      uneventful and successful with similar extraction efficiencies (median
      preapheresis collection efficiency [CE2], 36%) as in adult patients. At 58%,
      platelet attrition was considerable. CONCLUSION: Our data indicate that stem cell
      apheresis with the Spectra Optia MNC v.3.0 in very small donors is feasible,
      safe, and associated with very small product volumes.

PMID- 22882157
TI  - Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but
      not polyomavirus status correlates with outcome.
AB  - Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high
      associated mortality. Numerous studies have attempted to define characteristics
      to more accurately predict outcome. Two recent studies have demonstrated that
      Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better
      prognosis, while a third study revealed no difference. Expression of p63 by tumor
      cell nuclei has been shown to be associated with a worse prognosis in a European
      cohort. To better understand the relationship between prognosis and MCPyV or p63
      status, we used immunohistochemistry to evaluate both attributes in 36 US
      patients with MCC. Our results show that when considered as a binary variable,
      p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) =
      infinity) for shortened survival. In addition, our results show that MCPyV status
      does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates
      the European observation that p63 immunoexpression is useful as a prognostic
      tool. Larger studies will need to be performed in order to determine whether p63
      status should be included in MCC staging, since our study is limited by its
      relative small size.

PMID- 22882158
TI  - Prevention of arrhythmic death in valvular heart disease: beware the implantable
      defibrillator paradox.

PMID- 22882159
TI  - Molecular dynamics simulation of lysozyme adsorption/desorption on hydrophobic
      surfaces.
AB  - In this work, we present a series of fully atomistic molecular dynamics (MD)
      simulations to study lysozyme's orientation-dependent adsorption on polyethylene
      (PE) surface in explicit water. The simulations show that depending on the
      orientation of the initial approach to the surface the protein may adsorb or
      bounce from the surface. The protein may completely leave the surface or reorient
      and approach the surface resulting in adsorption. The success of the trajectory
      to adsorb on the surface is the result of different competing interactions,
      including protein-surface interactions and the hydration of the protein and the
      hydrophobic PE surface. The difference in the hydration of various protein sites
      affects the protein's orientation-dependent behavior. Side-on orientation is most
      likely to result in adsorption as the protein-surface exhibits the strongest
      attraction. However, adsorption can also happen when lysozyme's longest axis is
      tilted on the surface if the protein-surface interaction is large enough to
      overcome the energy barrier that results from dehydrating both the protein and
      the surface. Our study demonstrates the significant role of dehydration process
      on hydrophobic surface during protein adsorption. 

PMID- 22882160
TI  - Temporary inhibitory tagging at previously attended locations: evidence from
      event-related potentials.
AB  - Recent studies propose that a mechanism termed "inhibitory tagging" acts upon the
      processing of the target at the attended location by temporarily blocking the
      stimulus-response mapping. Here we combined the cue-target paradigm with the
      Stroop task and measured event-related potential (ERP) responses to the color of
      a color word presented at the previously attended (cued) or unattended (uncued)
      location. We found that the conflict-related N450 effect emerged later and had a
      smaller size at the cued than the uncued location. The overall ERP responses to
      the target showed lower P1 and N1 amplitude at the cued than the uncued location.
      Although the P1/N1 effect may reflect deficient perceptual processing of the
      target, the delay of the N450 suggests that the link between perceptual
      processing and response activation is temporarily blocked at the previously
      attended location.

PMID- 22882161
TI  - Drugs and the skin: psoriasis.

PMID- 22882163
TI  - Obesity in show dogs.
AB  - Obesity is an important disease with a growing incidence. Because obesity is
      related to several other diseases, and decreases life span, it is important to
      identify the population at risk. Several risk factors for obesity have been
      described in the literature. A higher incidence of obesity in certain breeds is
      often suggested. The aim of this study was to determine whether obesity occurs
      more often in certain breeds. The second aim was to relate the increased
      prevalence of obesity in certain breeds to the official standards of that breed.
      To this end, we investigated 1379 dogs of 128 different breeds by determining
      their body condition score (BCS). Overall, 18.6% of the show dogs had a BCS >5,
      and 1.1% of the show dogs had a BCS>7. There were significant differences between
      breeds, which could be correlated to the breed standards. It warrants firm
      discussions with breeders and judges in order to come to different
      interpretations of the standards to prevent overweight conditions from being the
      standard of beauty. 

PMID- 22882164
TI  - Fine-tuning the electronic structure of organic dyes for dye-sensitized solar
      cells.
AB  - A series of metal-free organic dyes exploiting different combinations of
      (hetero)cyclic linkers (benzene, thiophene, and thiazole) and bridges (4H
      cyclopenta[2,1-b:3,4-b']dithiophene (CPDT) and benzodithiophene (BDT)) as the
      central pi-spacers were synthesized and characterized. Among them, the sensitizer
      containing the thiophene and CPDT showed the most broad incident photon-to
      current conversion efficiency spectra, resulting in a solar energy conversion
      efficiency (eta) of 6.6%.

PMID- 22882165
TI  - Outcomes of gestational diabetes in Sweden depending on country of birth.
AB  - OBJECTIVE: To analyze maternal and neonatal outcomes for women with gestational
      diabetes mellitus (GDM) in Sweden, depending on country of birth (Nordic vs. non
      Nordic women). DESIGN: Population-based cohort study using the Swedish Medical
      Birth register. SETTING: Data on pregnant women in Sweden with diagnosed GDM.
      POPULATION: All singleton births to women with GDM between 1998 and 2007 (n =
      8560). METHODS: Logistic regression in an adjusted model to assess the risk of
      adverse maternal and neonatal outcomes. Chi-squared tests or Student's unpaired t
      tests were used to analyze differences between maternal and fetal
      characteristics. MAIN OUTCOME MEASURES: Maternal and neonatal complications.
      RESULTS: GDM incidence was higher at 2.0% among non-Nordic women, compared with
      0.7% in the Nordic group. The non-Nordic women were older, had less chronic
      hypertensive disease, smoked less, and had lower BMI and shorter height.
      Preeclampsia was significantly lower in the non-Nordic group. The mean
      birthweight (3561 vs. 3698 g, p < 0.001) and the large-for-gestational age rate
      (11.7 vs. 17.5%, p < 0.001) were significantly lower in the non-Nordic group.
      Large-for-gestational age was dependent on maternal height [crude odds ratio 0.6
      (0.5-0.7) and adjusted odds ratio 0.8 (0.6-0.9)]. CONCLUSIONS: Non-Nordic women
      with GDM in Sweden have better obstetrical and neonatal outcomes than Nordic
      women. These results do not support the idea of inequality of health care. Large
      for-gestational age as a diagnosis is highly dependent on maternal height, which
      raises the question of the need for individualized growth curves.

PMID- 22882166
TI  - Prescription drug use among pregnant women in opioid Maintenance Treatment.
AB  - AIMS: This study describes the use of prescribed drugs among women in opioid
      maintenance treatment (OMT) prior to, and during, pregnancy. DESIGN: This cohort
      study was based on data from two nationwide databases: the Medical Birth Registry
      of Norway and the Norwegian Prescription Database. SETTING: Norway, 2004-2010.
      PARTICIPANTS: OMT drugs were dispensed to 138 women with 159 pregnancies.
      MEASUREMENTS: All prescription drugs dispensed to women in OMT three months prior
      to, and during, pregnancy were studied. Amounts of benzodiazepines, z-hypnotics
      and opioid analgesics dispensed during pregnancy were studied and bivariate
      analysis was used to study neonatal outcomes of OMT pregnancies with and without
      such co-medication. FINDINGS: The prevalence of prescription drug use by pregnant
      OMT women was high both during the three-month period prior to (69%), and during
      (81%), pregnancy. The proportion of pregnant women that was dispensed anti
      infectives (48%) and/or drugs acting on the nervous system (45%) during any time
      in pregnancy was especially high. In 21%, 15% and 13% of the pregnancies the
      women were dispensed benzodiazepine anxiolytics, opioid analgesics or
      benzodiazepine hypnotics respectively. Only 5% of the OMT women were dispensed
      antidepressants. Malformations were significantly more common among children born
      to mothers in OMT that received co-medication with opioids, benzodiazepines or z
      hypnotics. CONCLUSIONS: A higher proportion of women in opioid maintenance
      treatment in Norway use prescription drugs prior to, and during, pregnancy than
      pregnant women in the general population. Co-medication with drugs with abuse
      potential may increase the risk of adverse pregnancy outcomes and this need to be
      further addressed.

PMID- 22882167
TI  - Presumed brain infarctions in two dogs with systemic leishmaniasis.
AB  - Clinical signs and magnetic resonance imaging findings of multiple brain infarcts
      in two dogs infected with Leishmania spp. are reported. Clinical signs of
      intracranial dysfunction were peracute and there was no further deterioration.
      Magnetic resonance images of the brain were consistent with multifocal, non
      haemorrhagic, ischaemic lesions. Routine serum biochemistry revealed
      hyperproteinaemia and hyperglobulinaemia. Serum antibody titres were highly
      positive for Leishmania infantum and Leishmania amastigotes were seen within bone
      marrow macrophages in both cases. Canine leishmaniasis can cause cerebrovascular
      alterations, such as vasculitis, that might predispose dogs to brain infarcts.

PMID- 22882168
TI  - Job satisfaction among dental therapists in South Africa.
AB  - OBJECTIVES: This article forms part of a larger research project on the dental
      therapy profession in South Africa. The objective of this study was to determine
      the level of job satisfaction among dental therapists trained at one South
      African university. METHODS: This study was conducted using the qualitative
      research approach, where purposive and convenience sampling was used to select
      interviewees. They were asked a single question: "Do you think that dental
      therapists in South Africa are satisfied within their present careers?" The
      narrative data was interpreted using thematic analysis, and the data was
      validated by using the markers of trustworthiness. RESULTS: All stakeholders
      believed that dental therapists trained at this university were not satisfied in
      the private and public sectors. In the private sector, they expressed frustration
      with their limited scope of practice. In the public service, lack of posts,
      poorly functioning dental facilities, and inadequate remuneration caused high
      levels of dissatisfaction. Many dental therapists chose this profession as a
      stepping stone to dentistry. CONCLUSIONS: The roles and scope of practice of all
      members of the oral health team needs to be redefined within the context of the
      primary health care approach. Universities need to recruit students appropriately
      to fulfill their role within this team. Dental services in the public sector need
      to be upgraded to meet the oral health needs of the country.

PMID- 22882169
TI  - Use and acute toxicity associated with the novel psychoactive substances
      diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP).
AB  - INTRODUCTION: Over the last decade there has been greater use of novel
      psychoactive substances ('legal highs') across Europe and the United States,
      including increasing reports of use of diphenylprolinol (D2PM) and
      desoxypipradrol (2-DPMP). This review will discuss the pharmacology and
      mechanisms of action of these two compounds, available data on their sources and
      prevalence of use and reports of acute toxicity and fatalities associated with
      their use. METHODS: PubMed was searched using the search terms 'D2PM', '2-DPMP',
      'diphenyl-2-pyrrolidinyl-methanol', 'diphenylprolinol', '2
      diphenylmethylpiperidine' and 'desoxypipradrol'. These searches identified 70
      articles, only five of which were relevant. PHARMACOLOGY AND MECHANISMS OF
      ACTION: D2PM is a pyrrolidine analogue and 2-DPMP is a desoxy analogue of
      pipradrol. Animal studies have shown that 2-DPMP increases the release of
      dopamine and decreases dopamine re-uptake comparable to the effects of cocaine.
      The binding and activity of D2PM at the dopamine re-uptake transporter, based on
      currently published data, is also similar to cocaine, although it appears that
      D2PM has less biological activity. SOURCES AND PREVALENCE OF USE: D2PM and 2-DPMP
      is available from internet-based suppliers and street level drug dealers; there
      is currently no systematic data to be able to determine the relative importance
      of these routes of supply. There is no population level, and limited
      subpopulation level, data on the prevalence of use of D2PM/2-DPMP. In one 2011
      study, 1.6% of 315 individuals in 'gay friendly' nightclubs in South London
      reported that they had used a pipradrol: 1.0% had used within the last year and
      0.6% had used or were planning to use a pipradrol on the night of the survey.
      ACUTE TOXICITY: Reports on internet discussion fora describe prolonged euphoria
      and stimulant effects including euphoria, sweating and bruxism with use of D2PM
      and 2-DPMP. The first report of analytically confirmed acute D2PM toxicity
      described chest pain and sympathomimetic features (hypertension and tachycardia).
      Five individuals with analytically confirmed acute D2PM toxicity developed
      agitation/anxiety and/or insomnia lasting 24-96 h in addition to sympathomimetic
      features (palpitations, anxiety and agitation). Reports of 49 enquiries relating
      to a 'legal high' product called 'Whack' (which on analysis was found to contain
      2-DPMP and fluorotropacocaine) commonly described unwanted cardiovascular
      (hypertension in 10/49 and tachycardia in 12/49) and neuropsychiatric (agitation
      in 14/49 and psychosis in 13/49) effects; the neuropsychiatric effects were
      prolonged, and persisted for up to 5 days. No analysis of biological samples was
      undertaken so it is not possible to determine which of these agents if any was
      responsible for the clinical features. In a series of 26 cases related to the use
      of 'Ivory Wave' (analysis of a similar 'Ivory Wave' product showed that it
      contained 2-DPMP), 96% had neuropsychiatric features. Cases presented up to 1
      week after use with tachycardia, dystonia, rhabdomyolysis, agitation,
      hallucinations and paranoia. Confirmatory biological sample analysis was either
      not available (85.3% of cases) or negative (2.9% of cases) for 2-DPMP; it was
      positive for 2-DPMP in four (11.8%) of the cases (80% of those where biological
      analysis was undertaken). D2PM AND 2-DPMP RELATED FATALITIES: Although 2-DPMP has
      been detected in three fatalities, its role in these deaths has not yet been
      established. There have been no reports of deaths directly attributed to either
      D2PM or 2-DPMP. CONCLUSIONS: There is emerging evidence of the use of D2PM and 2
      DPMP in Europe. D2PM and 2-DPMP have sympathomimetic properties similar to
      cocaine and, in addition, prolonged and clinically significant neuropsychiatric
      symptoms have been reported.

PMID- 22882170
TI  - Antihelical cartilage grafts for reconstruction of mohs micrographic surgery
      defects.
AB  - OBJECTIVE: To illustrate the safety, efficacy, and versatility of the antihelix
      as the preferred donor site for auricular cartilage autografts in the
      reconstruction of nasal and auricular Mohs micrographic surgery defects.
      MATERIALS AND METHODS: Retrospective chart review of all cartilage autografts
      performed at the Medical University of South Carolina for the 5-year period July
      1, 2006, to June 30, 2011; 307 auricular cartilage autografts were performed in
      297 patients. Each case was reviewed for demographic data, graft donor site,
      repair type, complications, and revisions. RESULTS: Three hundred five of the
      grafts (99.3%) were harvested from the antihelix and the remaining two (0.7%)
      from the conchal bowl. The donor site complication rate was 3%. No patients
      experienced cosmetic or functional deformity of the donor ear. No patients
      experienced cartilage graft resorption or infection. CONCLUSION: Antihelical
      cartilage grafts can serve as safe, effective, and versatile alternatives to
      septal, conchal bowl, and costal margin grafts. The authors feel strongly that
      the antihelix donor site should be favored when harvesting auricular cartilage
      for its easy accessibility, large dimension that may be harvested without
      aesthetic penalty, character of graft, and minimal operative morbidity.

PMID- 22882171
TI  - First eye cataract surgery and hospitalization from injuries due to a fall: a
      population-based study.
AB  - OBJECTIVES: To assess the association between first eye cataract surgery and
      hospitalization from injuries due to a fall in older adults at the population
      level. DESIGN: Retrospective population-based study. SETTING: Western Australian
      Hospital Morbidity Data System and Western Australian mortality data.
      PARTICIPANTS: Six hundred individuals aged 60 and older hospitalized from
      injuries due to a fall between 2004 and 2008 in Western Australia. MEASUREMENTS:
      Hospital admission from injuries due to a fall. RESULTS: Of the 15,295
      individuals who underwent cataract surgery in one eye only, 600 (3.9%) were
      involved in 625 hospital admissions from injuries due to a fall 1 year before (n
      = 273) or 1 year after (n = 352) first eye cataract surgery; 30% of these
      hospitalizations were for femoral neck fractures. Poisson generalized estimating
      equations confirmed 27% more (adjusted risk ratio = 1.27, 95% confidence interval
      = 1.04-1.56 P = .02) hospitalizations from injuries due to a fall in the year
      after first eye cataract surgery than in the year before. CONCLUSION: First eye
      cataract surgery was associated with more hospital admissions from injuries due
      to a fall in the year after cataract surgery than in the year before. Further
      research is needed to determine the underlying causes and reasons.

PMID- 22882172
TI  - Osmotic pressure can regulate matrix gene expression in Bacillus subtilis.
AB  - Many bacteria organize themselves into structurally complex communities known as
      biofilms in which the cells are held together by an extracellular matrix. In
      general, the amount of extracellular matrix is related to the robustness of the
      biofilm. Yet, the specific signals that regulate the synthesis of matrix remain
      poorly understood. Here we show that the matrix itself can be a cue that
      regulates the expression of the genes involved in matrix synthesis in Bacillus
      subtilis. The presence of the exopolysaccharide component of the matrix causes an
      increase in osmotic pressure that leads to an inhibition of matrix gene
      expression. We further show that non-specific changes in osmotic pressure also
      inhibit matrix gene expression and do so by activating the histidine kinase KinD.
      KinD, in turn, directs the phosphorylation of the master regulatory protein
      Spo0A, which at high levels represses matrix gene expression. Sensing a physical
      cue such as osmotic pressure, in addition to chemical cues, could be a strategy
      to non-specifically co-ordinate the behaviour of cells in communities composed of
      many different species.

PMID- 22882173
TI  - Niobium pentoxide as a new filler for methacrylate-based root canal sealers.
AB  - AIM: To evaluate the influence of several niobium pentoxide (Nb(2) O(5) )
      concentrations on the radio-opacity, flow, film thickness, microhardness and
      degree of conversion of an experimental root canal sealer. METHODOLOGY: An
      experimental dual-cured root canal sealer was produced with a methacrylate-based
      comonomer blend. Nb(2) O(5) was added at four different concentrations: 0, 80,
      100 and 120 wt%. Radio-opacity was evaluated according to ISO 6876 using a
      digital system (n = 5). Flow and film thickness were determined in accordance
      with ISO 6876 (n = 3). Microhardness was evaluated with 50 g for 15 s (n = 5).
      Degree of conversion was evaluated with FTIR immediately after photocuring and
      after 1, 7 and 14 days. The data were analysed using anova and Tukey's test. The
      degree of conversion over time was evaluated using RM-anova (alpha = 0.05).
      RESULTS: The groups with 80 wt% and 100 wt% of filler showed no significant
      difference in radio-opacity from that of equivalent 2 mmAl (P > 0.05). The
      addition of 120 wt% resulted in radio-opacity values higher than 2 mmAl (P <
      0.05). The flow was not significantly different amongst the different groups (P >
      0.05). All groups had a film thickness of <50 MUm (ISO 6876). All groups with
      Nb(2) O(5) were associated with higher values of microhardness than the control
      group. The group with 0 wt% was associated with a higher degree of conversion at
      all times. All groups except those with 80 wt% had higher values for degree of
      conversion after 14 days than immediately after photocuring. CONCLUSION: The
      addition of Nb(2) O(5) increases radio-opacity and microhardness; this material
      may be a promising filler for the production of a new endodontic sealer.

PMID- 22882174
TI  - Unilesional follicular mycosis fungoides: report of two cases with progression to
      tumor stage and review of the literature.
AB  - Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and has
      protean clinicopathological manifestations. Follicular or folliculotropic MF
      (FMF) is a rare variant, which histopathologically is characterized by pronounced
      folliculotropism of neoplastic T cells, with or without follicular mucinosis, and
      clinically by an impaired prognosis compared to classic MF. In contrast,
      unilesional MF is a very rare variant with an excellent prognosis, with a single
      case of large-cell transformation reported to date. The combination of
      folliculotropic and unilesional MF is very unusual, with only two cases reported
      to date. Here we report two patients with unilesional folliculotropic MF with
      progression to tumor stage in both patients. To the best of our knowledge, this
      is the first report on the disease evolution with large-cell transformation and
      progression of unilesional FMF. Complete remission was achieved by local
      radiation therapy in both patients. The differential diagnoses, classification
      and implications for the treatment of unilesional FMF as well as the pertinent
      literature are discussed.

PMID- 22882175
TI  - Validation of the exercise addiction inventory in a Danish sport context.
AB  - Exercise addiction is characterized by excessive exercise behavior with potential
      negative consequences. The symptoms consist of salience, mood modification,
      tolerance, withdrawal symptoms, conflicts, and relapse. The purpose of this study
      was to test the psychometric properties of the exercise addiction inventory (EAI)
      and to estimate the prevalence of exercise addiction in a Danish normal weight
      sport population. A sample of 780 habitual fitness and football exercisers were
      contacted and 590 completed the EAI and an in-house questionnaire containing
      questions about variables related to exercise addiction: (a) exercise frequency;
      (b) continuance despite injuries; and (c) personal perception of addiction. The
      results demonstrated an overall prevalence of exercise addiction of 5.8%. There
      was no significant difference between fitness and football prevalences. The
      internal reliability of EAI was acceptable with a Cronbach's alpha of 0.66. The
      criterion validity was tested toward the three variables related to exercise
      addiction. The dependent group had significantly higher scores on the three
      variables than the non-dependent group. Exercise addiction seems to exist in both
      fitness and football. The EAI is a useful screening tool and might be applicable
      in future screening and prevention of exercise addiction. However, further
      investigation about the population is needed to understand the phenomenon and to
      identify the risk group. 

PMID- 22882176
TI  - Economic evaluation of vaccination: capturing the full benefits, with an
      application to human papillomavirus.
AB  - Vaccination has been among the greatest contributors to the past century's
      dramatic improvements in health and life expectancy. Recent advances in
      vaccinology have resulted in new vaccines that will likely lead to substantial
      future health gains. However, the high cost of these new vaccines, such as the
      human papillomavirus (HPV) vaccine, poses an obstacle to their widespread
      adoption in many countries. Economic evaluation can help to determine if
      investment in vaccine introduction is worthwhile. However, existing economic
      evaluations usually focus on a narrow set of vaccination-mediated benefits-most
      notably avoided medical-care costs-and fail to account for several categories of
      potentially important gains. We consider three sources of such benefit and
      discuss them with respect to HPV vaccination: (i) outcome-related productivity
      gains, (ii) behaviour-related productivity gains, and (iii) externalities. We
      also highlight that HPV vaccination protects against more than just cervical
      cancer and that these other health gains should be taken into account. Failing to
      account for these broader benefits of HPV vaccination could result in substantial
      underestimation of the value of HPV vaccination, thereby leading to ill-founded
      decisions regarding its introduction into national immunization programmes.

PMID- 22882177
TI  - Reasons for moving toward a patient-centric paradigm of clinical transfusion
      medicine practice.
AB  - The combination of patient blood management (PBM) modalities and multicomponent
      apheresis permits us to administer even safer transfusions than those using the
      "safer-than-ever" blood components distributed in the beginning of the 21st
      century. PBM identifies a patient at risk of transfusion and formulates a
      multidisciplinary and multimodal-yet individualized-plan for reducing the need
      for allogeneic transfusion. Multicomponent apheresis can collect any combination
      of red blood cells, platelets, and plasma from the same donor during the same
      donation, and it should eventually reserve all components harvested from the same
      donation for transfusion to the same recipient. Together, PBM and multicomponent
      apheresis represent a new paradigm-the patient-centric paradigm-of transfusion
      medicine whose purpose is to reduce the transfusion risk for each individual
      patient to the level of the ALARA (as-low-as-reasonably-achievable) risk. PBM and
      multicomponent apheresis can meet a patient's transfusion needs with at least
      twofold fewer allogeneic donor exposures, thereby reducing the risk of infectious
      and immunologic complications of transfusion by at least twofold. The reduction
      in risk includes the leading cause of transfusion-related mortality (transfusion
      related acute lung injury) and the cardinal threat to transfusion safety (the
      next "HIV-like" pathogen to emerge in the future). Once it is determined that PBM
      and multicomponent apheresis can replace the current blood-procurement system at
      a "reasonable" cost and without jeopardizing the supply of blood and components,
      the patient-centric paradigm should replace the current, component-centric
      paradigm of transfusion medicine to reduce the transfusion risk to the level of
      the ALARA risk.

PMID- 22882178
TI  - Participation of haemocytes in fat body degradation via cathepsin L expression.
AB  - Insect haemocytes are known to participate in innate immunity via the
      phagocytosis of pathogens. However, the function of haemocytes in tissue
      remodelling is less understood. We report here that haemocytes play roles in fat
      body degradation by expressing a cysteine proteinase cathepsin L in the
      lepidopteran Helicoverpa armigera. During metamorphosis, haemocytes undergo
      morphological changes by increasing their cell size and transforming their
      granulocytes into macrogranulocytes. The population of haemocytes also changes
      with increased number of granulocytes and decreased plasmatocytes. The expression
      level of cathepsin L in haemocytes, mainly in granulocytes and plasmatocytes,
      increases. The steroid hormone 20-hydroxyecdysone is able to promote the
      transformation of granulocytes into macrogranulocytes, and up-regulate the
      expression level of cathepsin L. The knock-down of the cathepsin L gene by RNA
      interference in haemocytes in vitro results in deficient granulocytes
      transforming into macrogranulocytes. Haemocytes are able to enter the decomposed
      fat body during metamorphosis. The over-expression of the proteinase domain C1A
      of cathepsin L results in cell apoptosis. Haemocytes, especially
      macrogranulocytes, undergo apoptosis and cathepsin L is released into haemolymph
      and the fat body during metamorphosis for fat body decomposition and degradation.
      These results suggest that cathepsin L is related to the transformation of
      granulocytes to macrogranulocytes to enter the fat body, and induce haemocyte
      apoptosis for further tissue degradation.

PMID- 22882179
TI  - A wide QRS complex tachycardia and group beating in a young patient with heart
      failure: what is the mechanism?

PMID- 22882180
TI  - Specific histological abnormalities are more likely in biopsies of endoscopically
      normal large bowel after the age of 60 years.
AB  - AIMS: Colonic and rectal biopsies, often taken from an endoscopically normal
      large bowel, form a significant proportion of the histopathology workload. The
      aim of this study was to determine diagnostic yield from mucosal biopsies in
      patients with normal colonoscopy or sigmoidoscopy, and whether or not diarrhoea
      is predictive of abnormal histology. METHODS AND RESULTS: A retrospective
      analysis of pathology requests, endoscopy and pathology reports taken during 1
      year was undertaken in a tertiary care hospital for all biopsies from
      endoscopically normal ileal, colonic and rectal mucosa. Of 626 patients
      fulfilling inclusion criteria, 602 had at least one colonic or rectal biopsy.
      Colorectal histology was abnormal in 65 (14.5%) of 447 patients with diarrhoea,
      while of 155 patients without diarrhoea, histology was abnormal in 17 (11%;
      P=0.41). Patients older than 60 years had a markedly increased likelihood of a
      specific histological abnormality [odds ratio 2.76 (1.30-5.79); P=0.0045].
      Diagnoses included microscopic colitis, distorted mucosal architecture consistent
      with inflammatory bowel disease, ischaemia, polyps, mucosal prolapse and
      schistosomiasis. CONCLUSIONS: Biopsy of an endoscopically normal large bowel, and
      of the normal terminal ileum in isolation, yields little abnormal histology.
      Diarrhoea per se does not identify patients at higher risk of abnormal histology.
      Increased age, however, does, and mucosal biopsy in the endoscopically normal
      colon and rectum may be more cost-effective in patients aged more than 60 years.

PMID- 22882181
TI  - Suspected primary glioblastoma multiforme in the canine spinal cord.
AB  - An eight-year-old mixed-breed dog was presented with progressive paraparesis.
      Neurological examination revealed a painful diffuse lesion between spinal cord
      segments T3 and L3. Magnetic resonance images displayed multi-focal contrast
      enhancing spinal cord and meningeal lesions. Cytology of these lesions revealed a
      malignant tumour prompting euthanasia of the dog. Histopathology confirmed the
      cytological diagnosis and a final diagnosis of a glioblastoma multiforme was made
      based on immunohistochemistry.

PMID- 22882182
TI  - Evaluation of a multicomponent intervention to improve weight status and fitness
      in children: Upstarts.
AB  - BACKGROUND: Many physical activity intervention programs are unable to sustain
      long-term improvements in activity levels and are often not cost-effective. The
      aim of this study was to determine if a low-cost school- and community-centered
      sports coaching program was able to improve health-related fitness in children.
      METHODS: Children from three schools in socially deprived areas took part in
      weekly coaching sessions over two 10 week periods during the school year.
      Coaching was provided by local community-based sports clubs. Body mass index
      (BMI), jump height, handgrip strength, and 20 m shuttle run test (20mSRT)
      performance were assessed before and after each of the two intervention periods,
      to determine short- and long-term changes in health-related fitness. Age- and sex
      normalized z-scores were calculated using normative UK reference data for each
      measure. RESULTS: BMI z-score did not change in the short term, as expected, but
      importantly was significantly lower at the end of the study. Both handgrip and
      20mSRT performance scores increased after the first 10 week period. Only
      improvements in handgrip were maintained for the whole study period. Jump height
      actually decreased over the entire study period. CONCLUSION: There were some
      notable benefits of this novel, cost-effective, naturalistic intervention but
      future studies should examine seasonal variation and motivational factors as
      potential confounding variables.

PMID- 22882184
TI  - On the importance of blood sampling for ciclosporin pharmacokinetic studies.

PMID- 22882185
TI  - Why urease is a di-nickel enzyme whereas the CcrA beta-lactamase is a di-zinc
      enzyme.
AB  - Ureases and metallo-beta-lactamases are amide hydrolases closely related in
      function and structure. However, one major difference between them is that the
      former uses two nickel cations, and the latter uses two zinc cations to do
      similar catalytic jobs. What is the reason for this choice that Nature made for
      the catalytic metals? Is it dictated by electronic or structural reasons in the
      two catalyzed reactions, or some other evolutionary factors? Are both enzymes
      "perfect" catalysts, as far as just catalysis is concerned, and if they are, then
      why? Here, we address these questions through a joint quantum
      mechanical/molecular mechanical dynamics approach and ab initio mechanistic
      investigation. Five enzyme/substrate systems are considered: urease/urea, CcrA
      beta-lactamase/beta-lactam antibiotic model, urease/beta-lactam antibiotic model,
      CcrA beta-lactamase/urea, and di-Ni-substituted CcrA beta-lactamase/beta-lactam
      antibiotic model. The mechanisms and rates of the metal-facilitated nucleophilic
      attack are assessed. Both urease and Ni-substituted beta-lactamase catalyze the
      attack on the beta-lactam ring with the efficiency surpassing that of natural di
      Zn beta-lactamase, whereas beta-lactamase is unable to hydrolyze urea. These
      results suggest that in beta-lactamases the use of zinc does not provide maximal
      possible efficiency of the enzyme. Thus, beta-lactamases operate by the principle
      of "good enough"; i.e., the choice for Zn in them leads to a performance that is
      just satisfactory for its biological purpose but can be evolutionarily improved
      via replacement of Zn with Ni.

PMID- 22882183
TI  - A mutation in Drosophila Aldolase causes temperature-sensitive paralysis,
      shortened lifespan, and neurodegeneration.
AB  - We describe the characterization of m4, an autosomal recessive, temperature
      sensitive paralytic mutant in Drosophila that is associated with shortened
      lifespan and neurodegeneration. Deletion mapping places the mutation in the gene
      encoding the glycolytic enzyme, Aldolase. The mutant enzyme contains a single
      amino acid substitution, which results in decreased steady-state levels of
      Aldolase with a consequent reduction in adenosine triphosphate (ATP) levels.
      Transgenic-rescue experiments with a genomic construct containing the entire
      Aldolase gene confirm that paralysis, reduced lifespan, and neurodegeneration all
      result from the same mutation. Tissue-specific rescue and RNA interference (RNAi)
      knockdown experiments indicate that Aldolase function (and presumably glycolysis)
      is important both in neurons and in glia for normal lifespan and neuronal
      maintenance over time. Impaired glycolysis in neurons can apparently be rescued
      in part by glycolytically active glia. However, this rescue may depend on the
      exact physiological state of the neurons and may also vary in different subsets
      of neurons. Further studies of m4 and related mutants in Drosophila should help
      elucidate the connections between energy production and utilization in glia and
      neurons and lead to better understanding of how metabolic defects impair neuronal
      function and maintenance.

PMID- 22882186
TI  - Photocurrent generation in carbon nitride and carbon nitride/conjugated polymer
      composites.
AB  - The semiconductor and photovoltaic properties of carbon nitride (CNx) thin films
      prepared using a reactive magnetron cathodic sputtering technique were
      investigated both individually and as composites with an organic conjugated
      polymer, poly(2,2'-bithiophene) (PBT). The CNx films showed an increasing
      thickness as the deposition power and/or nitrogen content in the gas mixture
      increase. At low nitrogen content and low deposition power (25-50 W), the film
      structure was dominated by the abundance of the graphitic sp(2) regions, whereas
      at higher nitrogen contents and magnetron power CNx films started to demonstrate
      semiconductor properties, as evidenced by the occurrence of photoconductivity and
      the development of a space charge region. However, CNx films alone did not show
      any reproducible photovoltaic properties. The situation changed, however, when
      CNx was deposited onto conjugated PBT substrates. In this configuration, CNx was
      found to function as an acceptor material improving the photocurrent generation
      both in solution and in solid state photovoltaic devices, with the external
      quantum efficiencies reaching 1% at high nitrogen contents. The occurrence of the
      donor-acceptor charge transfer was further evidenced by suppression of the n
      doping of the PBT polymer by CNx. Nanoscale atomic force microscopy (AFM) and
      current-sensing AFM data suggested that CNx may form a bulk heterojunction with
      PBT.

PMID- 22882187
TI  - Anaerobic oxidation of methane in hypersaline cold seep sediments.
AB  - Life in hypersaline environments is typically limited by bioenergetic
      constraints. Microbial activity at the thermodynamic edge, such as the anaerobic
      oxidation of methane (AOM) coupled to sulphate reduction (SR), is thus unlikely
      to thrive in these environments. In this study, carbon and sulphur cycling was
      investigated in the extremely hypersaline cold seep sediments of Mercator mud
      volcano. AOM activity was partially inhibited but still present at salinity
      levels of 292 g L(-1) (c. eightfold sea water concentration) with rates of 2.3
      nmol cm(-3) day(-1) and was even detectable under saturated conditions. Methane
      and evaporite-derived sulphate comigrated in the ascending geofluids, which, in
      combination with a partial activity inhibition, resulted in AOM activity being
      spread over unusually wide depth intervals. Up to 79% of total cells in the AOM
      zone were identified by fluorescence in situ hybridization (FISH) as anaerobic
      methanotrophs of the ANME-1. Most ANME-1 cells formed monospecific chains without
      any attached partner. At all sites, AOM activity co-occurred with SR activity and
      sometimes significantly exceeded it. Possible causes of these unexpected results
      are discussed. This study demonstrates that in spite of a very low energy yield
      of AOM, microorganisms carrying this reaction can thrive in salinity up to halite
      saturation.

PMID- 22882188
TI  - Effect of wheat processing on rumen characteristics and rumen parameters in
      Holstein-Friesian calves.
AB  - In this experiment, effect of wheat processing on rumen conditions and
      development were investigated. Fifty-six neonatal Holstein-Friesian calves (22
      male and 34 female) were fed calf starters and post-weaning diets containing 35
      (pre-weaning) and 21.90% (post-weaning) popped wheat (PW), steam-flaked wheat
      (SFW), dry-rolled wheat (DRW) or ground wheat (GW) till 12 weeks of age. Calves
      were weaned at the end of 9th week, and a post-weaning-specific starter diets
      were fed for 1 month. Rumen liquor was analysed in days 30, 60 and 90 of the
      experiment to determine volatile fatty acids (VFA), pH and ammonia nitrogen
      concentrations. Twelve male calves (three calves/treatment) were slaughtered, and
      digestive tract was emptied. Forestomach empty weight and rumen parameters were
      assessed. Results indicated that calves received PW had the highest total VFA,
      acetate, propionate, butyrate, ammonia nitrogen, rumen wall thickness, papilla
      width and density. Calves fed DRW experienced the lowest rumen pH throughout the
      experiment probably because high proportion of fine particles in GW. Calves
      consuming PW apparently had more functional rumen in comparison with other
      groups. 

PMID- 22882189
TI  - An ERP study of coreference in Spanish: semantic and grammatical gender cues.
AB  - We report two event-related potentials (ERPs) experiments aimed to investigate
      the roles played by semantic and syntactic information during pronoun resolution.
      The first experiment was designed to show that ambiguity of the pronoun (e.g.,
      word class ambiguity) makes an important contribution to the pattern observed in
      previous ERP studies. As expected, the results showed a different ERP pattern for
      ambiguous and nonambiguous pronouns. The second experiment analyzed pronoun
      resolution when gender agreement and animacy were manipulated, using only
      unambiguous pronouns. Results showed P600 effects at 500 to 700 ms and at 700 to
      900 ms. Amplitude of the second window was significantly greater for animate than
      for inanimate antecedents. The modulation of the agreement effect by animacy
      suggests that repair processes after grammatical disagreement detection are
      influenced by semantics.

PMID- 22882190
TI  - Assessment of methotrexate hepatotoxicity in psoriasis patients: a prospective
      evaluation of four serum fibrosis markers.
AB  - BACKGROUND: Low-dose oral methotrexate (MTX) is an effective immunosuppressive
      therapy for chronic plaque psoriasis. However, its use is hampered by the risk of
      liver fibrosis. AIM: To compare the results of serial measurements of serum
      fibrosis markers during the remission-induction phase of treatment with MTX to
      those of patients on biological therapy and long-term MTX therapy (>2 years).
      SUBJECTS AND METHODS: Serum concentrations of hyaluronic acid, N-terminal
      propeptide of collagen type III (PIIINP) and the results of two multi-test
      algorithms Fibrotest and Hepascore were evaluated in patients with chronic plaque
      psoriasis (N = 24, age: 28-79 years, baseline Psoriasis Area Severity Index PASI
      13.5, range 2.2-33) at baseline and weeks 16 and 26 after the start of
      pharmacokinetically guided therapy with MTX (Group A). Patients on established
      therapy with biologics (N = 15, Group B) and long-term MTX users (N = 10, Group
      C) with the mean baseline PASI scores of 0.9 and 1.2 were studied in parallel
      cohorts. RESULTS: At baseline, HA, Hepascore and PIIINP were correlated with PASI
      of Group A patients. At weeks 16 and 26, HA decreased by 48% and 40% (P < 0.001)
      and Hepascore by 31 (P < 0.01) and 20% (P < 0.05) respectively. PASI75 (>= 75%
      improvement from baseline PASI) was observed in 76% of Group A patients by week
      26 and the absolute decreases in PASI and both fibrosis markers were correlated
      (HA: r = 0.49, P = 0.018, Hepascore: r = 0.47, P = 0.022). In contrast, no
      significant within-group differences were found in HA and Hepascore results of
      patients in the groups B and C. PIIINP and Fibrotest were stable in all groups.
      CONCLUSION: The fibrosis markers hyaluronic acid and Hepascore (the multiple test
      algorithm which includes hyaluronic acid) are less liver specific and more prone
      to reflect psoriasis activity than PIIINP and Fibrotest.

PMID- 22882191
TI  - Reoccurrence of retained placenta at vaginal delivery: an observational study.
AB  - OBJECTIVE: To estimate the prevalence and validate the diagnosis of retained
      placenta in nulliparous women and the risk of reoccurrence at subsequent vaginal
      delivery. DESIGN: Nested cohort study. SETTING: Department of Gynecology and
      Obstetrics, university-affiliated teaching hospital. POPULATION: 10 334
      nulliparous singleton pregnancies who delivered vaginally at the hospital during
      2000-2009. METHODS: Data from a computerized database information system were
      used to identify 287 women who had an ICD-10 diagnosis of retained placenta and
      572 randomly selected controls matched by the date of first delivery. At chart
      review the diagnosis was confirmed by: (1) excessive bleeding <30 minutes after
      delivery without placental separation, (2) placenta not separated 30 minutes
      after delivery or (3) confirmation of retained placental tissue >2 hours
      postpartum. MAIN OUTCOME MEASURES: Confirmation of the diagnosis and prevalence
      of retained placenta. Risk of reoccurrence in a subsequent vaginal delivery.
      RESULTS: The prevalence of retained placenta increased from 2.8 to 7.0% after
      confirmation according to the set criteria. Of the selected women, 48.4% had a
      subsequent vaginal delivery. Of these women, 25.3% (23/91) with a previous
      retained placenta and 5.3% (11/206) without previously retained placenta,
      experienced retained placenta in subsequent delivery. This corresponds to an
      adjusted odds ratio of 5.5 (95% confidence interval 2.6-12.7) in the multivariate
      analysis for recurrence of retained placenta in a subsequent vaginal delivery.
      CONCLUSIONS: The use of the ICD-10 diagnosis of retained placenta underestimated
      the prevalence. The risk of reoccurrence of retained placenta is significantly
      increased in a subsequent vaginal delivery.

PMID- 22882192
TI  - Molecular prognostic markers in gallbladder carcinoma.

PMID- 22882193
TI  - Nuclear expression of thioredoxin-1 in the invasion front is associated with
      outcome in patients with gallbladder carcinoma.
AB  - BACKGROUND: Multifunctional redox protein human thioredoxin (TRX-1) is reduced by
      thioredoxin reductase (TRX-R). The aim of the present study was to examine the
      distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to
      clarify their usefulness as prognostic factors after surgical resection. METHODS:
      Immunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from
      38 patients who underwent surgical resection, and TRX-1/TRX-R localization in
      relation to outcome was examined. RESULTS: TRX-1 protein levels were
      significantly higher in GBC samples than in cholecystolithiasis samples (P =
      0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in
      the nucleus in 76% (29/38), with nuclear expression in the invasion front
      observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of
      cancer cells and in the invasion front in 28 samples. In all of the samples, the
      depth of tumour invasion, lymph node metastasis, surgical margin, curability and
      nuclear expression of TRX-1 in the invasion front were significant prognostic
      factors by univariate analysis. In 27 selected patients who underwent curative
      resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the
      invasion front was a significantly prognostic factor. CONCLUSION: TRX-1 nuclear
      expression in the GBC invasion front is a significant prognostic marker. Patients
      with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour
      invasion front should be observed carefully even if after curative resection.

PMID- 22882194
TI  - The safety of a pancreaticoduodenectomy in patients older than 80 years: risk vs.
      benefits.
AB  - BACKGROUND: A pancreaticoduodenectomy (PD) offers the only chance of a cure for
      pancreatic cancer and can be performed with low mortality and morbidity. However,
      little is known about outcomes of a PD in octogenarians. METHODS: Differences in
      two groups of patients (Group Y, <80 and Group O, >=80 year-old) who underwent a
      PD for pancreatic adenocarcinoma were analysed. Study end-points were length of
      post-operative stay, overall morbidity, 30-day mortality and overall survival.
      RESULTS: There were 175 patients in Group Y (mean age 64 years) and 25 patients
      in Group O (mean age 83 years). Octogenarians had worse Eastern Cooperative
      Oncology Group (ECOG) Performance Status (PS >=1: 90% vs. 51%) and American
      Society of Anesthesiology (ASA) score (>2: 71% vs. 47%). The two groups were
      similar in underlying co-morbidities, operative time, rates of portal vein
      resection, intra-operative complications, blood loss, pathological stage and
      status of resection margins. Octogenarians had a longer post-operative stay (20
      vs. 14 days) and higher overall morbidity (68% vs. 44%). There was a single death
      in each group. At a median follow-up of 13 months median survival appeared
      similar in the two groups (17 vs. 13 months). CONCLUSIONS: As 30-day mortality
      and survival are similar to those observed in younger patients, a PD can be
      offered to carefully selected octogenarians.

PMID- 22882195
TI  - Toward defining grade C pancreatic fistula following pancreaticoduodenectomy:
      incidence, risk factors, management and outcome.
AB  - BACKGROUND: In 2005 the International Study Group for Pancreatic Fistula (ISGPF)
      created a definition and grading system for pancreatic fistulae (PF) in which
      grade C denotes the most severe and potentially life-threatening type. Factors
      and outcomes associated with grade C fistulae have been ill defined. METHODS:
      Systematic searches of PubMed and EMBASE were conducted by two independent
      reviewers utilizing the keywords 'pancreaticoduodenectomy' (PD) and 'pancreatic
      fistula'. Inclusion criteria were: (i) a sample of >=100 patients; (ii)
      consecutive accrual of all pathologies, and (iii) use of the ISGPF definition and
      grading system. Quality appraisal and data extraction were performed using pilot
      tested templates. RESULTS: Fourteen articles describing a total of 2706 PDs met
      the study entrance criteria. Pancreatic fistulae occurred in 479 patients (18%)
      and included 71 grade C PF that were directly responsible for 25 deaths (35%
      mortality rate). Only two studies analysed risk factors; these found soft
      pancreatic texture and histology other than adenocarcinoma to be the most common
      risk factors. Ten studies reported management strategies and indicated that 51%
      of patients required reoperation. CONCLUSIONS: Grade C PF: (i) accounts for 15%
      of fistulae following PD and has an associated mortality rate of 35%; (ii) occurs
      most commonly in pathology associated with a soft remnant, and (iii) requires
      reoperation in approximately one half of patients. The published literature
      incompletely describes grade C PF.

PMID- 22882196
TI  - Image-guided liver surgery: intraoperative projection of computed tomography
      images utilizing tracked ultrasound.
AB  - BACKGROUND: Ultrasound (US) is the most commonly used form of image guidance
      during liver surgery. However, the use of navigation systems that incorporate
      instrument tracking and three-dimensional visualization of preoperative
      tomography is increasing. This report describes an initial experience using an
      image-guidance system with navigated US. METHODS: An image-guidance system was
      used in a total of 50 open liver procedures to aid in localization and targeting
      of liver lesions. An optical tracking system was employed to localize surgical
      instruments. Customized hardware and calibration of the US transducer were
      required. The results of three procedures are highlighted in order to illustrate
      specific navigation techniques that proved useful in the broader patient cohort.
      RESULTS: Over a 7-month span, the navigation system assisted in completing 21
      (42%) of the procedures, and tracked US alone provided additional information
      required to perform resection or ablation in six procedures (12%). Average
      registration time during the three illustrative procedures was <1 min. Average
      set-up time was approximately 5 min per procedure. CONCLUSIONS: The ExplorerTM
      Liver guidance system represents novel technology that continues to evolve. This
      initial experience indicates that image guidance is valuable in certain
      procedures, specifically in cases in which difficult anatomy or tumour location
      or echogenicity limit the usefulness of traditional guidance methods.

PMID- 22882197
TI  - Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort
      study.
AB  - BACKGROUND: Treatment requirements in hepatolithiasis may vary and may involve a
      multidisciplinary approach. Surgical resection has been proposed as a definitive
      treatment. OBJECTIVES: This study aimed to evaluate the clinical results of
      anatomic liver resection among Chilean patients with hepatolithiasis. METHODS: An
      historical cohort study was conducted. Patients who underwent hepatectomy as a
      definitive treatment for hepatolithiasis from January 1990 to December 2010 were
      included. Patients with a preoperative diagnosis of cholangiocarcinoma were
      excluded. Preoperative, operative and postoperative variables were evaluated.
      RESULTS: A total of 52 patients underwent hepatectomy for hepatolithiasis. The
      mean +/- standard deviation patient age was 49.8 +/- 11.8 years (range: 24-78
      years); 65.4% of study subjects were female. A total of 75.0% of subjects had a
      history of previous cholecystectomy. The main presenting symptom was abdominal
      pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right
      lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative
      clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and
      there were no postoperative deaths. Three patients had recurrence of
      hepatolithiasis, which was associated with Caroli's disease in two of them.
      Overall 5-year survival was 94.5%. CONCLUSIONS: Anatomic liver resection is an
      effective treatment in selected patients with hepatolithiasis and is associated
      with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy
      in these patients was associated with a lower rate of recurrence.

PMID- 22882198
TI  - Randomized clinical trial of local infiltration plus patient-controlled opiate
      analgesia vs. epidural analgesia following liver resection surgery.
AB  - OBJECTIVES: Epidural analgesia is recommended for the provision of analgesia
      following major abdominal surgery. Continuous local anaesthetic wound
      infiltration may be an effective alternative. A prospective randomized trial was
      undertaken to compare these two methods following open liver resection. The
      primary outcome was length of time required to fulfil criteria for discharge from
      hospital. METHODS: Patients undergoing open liver resection were randomized to
      receive either epidural (EP group) or local anaesthetic wound infiltration plus
      patient-controlled opiate analgesia (WI group) for the first 2 days
      postoperatively. All other care followed a standardized enhanced recovery
      protocol. Time to fulfil discharge criteria, pain scores, physical activity
      measurements and complications were recorded. RESULTS: Between August 2009 and
      July 2010, 65 patients were randomized to EP (n = 32) or WI (n = 33). The mean
      time required to fulfil discharge criteria was 4.5 days (range: 2.5-63.5 days) in
      the WI group and 6.0 days (range: 3.0-42.5 days) in the EP group (P = 0.044).
      During the first 48 h following surgery, pain scores were significantly lower in
      the EP group both at rest and on movement. Resting pain scores within both groups
      were rated as mild (range: 0-3). There was no significant difference between the
      groups in time to first mobilization or overall complication rate (48.5% in the
      WI group vs. 58.1% in the EP group; P = 0.443). CONCLUSIONS: Local anaesthetic
      wound infiltration combined with patient-controlled opiate analgesia reduces the
      length of time required to fulfil criteria for discharge from hospital compared
      with epidural analgesia following open liver resection. Epidural analgesia
      provides superior analgesia, but does not confer benefits in terms of faster
      mobilization or recovery.

PMID- 22882199
TI  - Effects of donor steatosis on liver biochemistry and significance of body mass
      index in predicting steatosis.
AB  - BACKGROUND: Hepatic steatosis is a major concern in living donor liver
      transplantation. Factors affecting hepatic functional status after a donor right
      hepatectomy (with the middle hepatic vein included in the graft) with a focus on
      changes owing to steatosis were retrospectively studied. METHODS: Donors (n =
      325) were categorized into three groups: G0 (no steatosis, n = 178), G1 (< = 10%
      steatosis, n = 128) and G2 (>10% steatosis, n = 19). Donors with >20% steatosis
      were excluded. Changes in aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), bilirubin levels and prothrombin time (PT) were assessed.
      Factors predicting steatosis were also assessed. A liver biopsy was performed on
      selected donors. RESULTS: The ALT level rose until day 3 in G1 and day 6 in G2 (P
      < 0.05). The AST level rose until day 7 in G2 (P < 0.05) but stayed unchanged in
      G1. The bilirubin level was higher only on day 1 in G2 (P < 0.05). By day 30, no
      significant difference between any groups was noted. Receiver-operating
      characteristic (ROC) area under the curve for body mass index (BMI) on predicting
      steatosis was 0.75 [confidence interval (CI) = 69-80]. Among donors with a BMI >
      23.5 kg/m(2), 75% had steatosis. Five donors had >20% steatosis and were not
      assessed. CONCLUSION: Using a liver with up to 20% steatosis in right liver
      donation, even if the middle hepatic vein is included in the graft, is safe. For
      Asian donors, a BMI > 23.5 kg/m(2) is a guide in deciding whether to perform a
      liver biopsy for steatosis.

PMID- 22882200
TI  - Equivalent survival following liver transplantation in patients with non
      alcoholic steatohepatitis compared with patients with other liver diseases.
AB  - BACKGROUND: Orthotopic liver transplantation (LT) in non-alcoholic
      steatohepatitis (NASH) is increasing in parallel with the obesity epidemic.
      METHODS: This study retrospectively reviewed the clinical outcomes of LTs in NASH
      (n = 129) and non-NASH (n = 775) aetiologies carried out at a single centre
      between 1999 and 2009. RESULTS: Rates of 1-, 3- and 5-year overall survival in
      NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH
      (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was
      twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P = 0.04). Compared
      with non-NASH patients, post-LT mortality in NASH patients was more commonly
      caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05)
      aetiologies. Five-year survival was lower in NASH patients with a high-risk
      phenotype (age >60 years, body mass index >30 kg/m(2), with hypertension and
      diabetes) than in NASH patients without these characteristics (72% vs. 87%; P =
      0.02). Subgroup analyses revealed that 5-year overall survival in NASH was
      equivalent to that in Laennec's cirrhosis (85% vs. 80%; P 0.87), but lower than
      that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P = 0.04). CONCLUSIONS:
      Orthotopic LT in NASH was associated with increased early postoperative
      mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those
      in non-NASH patients.

PMID- 22882201
TI  - Comparison of outcomes of transplantation and resection in patients with early
      hepatocellular carcinoma: a meta-analysis.
AB  - OBJECTIVES: Surgical decision making for patients with early hepatocellular
      carcinoma (HCC) and well-compensated cirrhosis remains controversial. The aim of
      the current study was to conduct a meta-analysis of published reports to compare
      survival outcomes after transplantation and resection, respectively, in patients
      with early HCC [i.e. HCC falling within the Milan Criteria (a solitary lesion
      measuring <=5 cm or fewer than three lesions with a largest diameter of <=3 cm,
      and absence of macroscopic vascular invasion or extrahepatic disease)] and well
      compensated cirrhosis. METHODS: A total of 990 abstracts were identified through
      a PubMed-based search. Ten articles comparing transplantation and resection in
      patients with early HCC were included in the meta-analysis. Meta-analysis was
      performed using stata 9.2 statistical software. RESULTS: Outcomes were analysed
      for a total of 1763 patients with early HCC. The 5-year overall survival (OS) for
      all patients was 58% (transplantation: 63%; resection: 53%). Meta-analysis of all
      10 studies revealed a survival advantage for transplantation [odds ratio (OR)
      0.581, 95% confidence interval (CI) 0.359-0.939; P = 0.027]. Analysis of only
      those reports that utilized an 'intention-to-treat' strategy failed to
      demonstrate a survival advantage for either treatment approach (OR 0.600, 95% CI
      0.291-1.237; P = 0.166). CONCLUSIONS: The current study demonstrates a favourable
      outcome in patients with early HCC treated by either transplantation or
      resection. Although transplantation was noted to have a survival advantage in
      some settings, resection continues to be a viable treatment approach.

PMID- 22882204
TI  - The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic
      target?
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with
      long-term health risks, including type 2 diabetes and vascular dysfunction in
      addition to reproductive sequelae. Many of the common features of PCOS, such as
      central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are
      associated with chronic sympathetic overactivity, suggesting that
      sympathoexcitation may be involved in the pathogenesis of this condition. Rodent
      models of polycystic ovaries have shown that ovarian sympathetic outflow may be
      increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor
      (NGF) which may be involved in initiation of ovarian pathology. Patients with
      PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered
      heart rate variability and attenuated heart rate recovery postexercise, compared
      with age- and BMI-matched controls, suggesting a generalized increase in
      sympathetic nerve activity. Active weight loss can reduce MSNA and whole body
      noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA
      in overweight women with PCOS. Treatment of OSA with continuous positive airways
      pressure may reduce plasma noradrenaline levels and diastolic blood pressure and
      improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced
      MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with
      hypertension, accompanied by improved insulin sensitivity. The sympathetic
      nervous system may thus offer a new therapeutic target in PCOS but larger and
      longer-term studies are needed before these treatments can be considered in
      clinical practice.

PMID- 22882205
TI  - The prevalence of chronic and episodic migraine in children and adolescents.
AB  - BACKGROUND AND PURPOSE: Migraine is the most important cause of headache leading
      to a decrease in the quality of life in children and adolescents. The prevalence
      of episodic (EM) and chronic migraine (CM) increases with increasing age, which
      especially focused in recent years. METHODS: To evaluate the prevalence and
      determinants of migraine in children and adolescents, we performed this school
      based epidemiological study. First part of the study was performed in 2001 that
      included 5562 children. Second part of the study was performed in 2007 in
      adolescents including 1155 young. After the main reports published, we made a new
      analysis in the database that focused on migraine. RESULTS: Totally, 10.4% of the
      children, predominantly the girls, received the diagnosis of migraine when they
      grew older (1.7% CM, 8.6% EM). CM frequency increased with increasing ages
      (doubled at 12 years, P = 0.035). The significant risk factors for having CM were
      found to be age, gender, and father and sibling headache histories. Most of the
      clinical characteristics of migraine are far from classical knowledge in children
      with CM. In adolescents, 18.6% were diagnosed as migraine (1.5%CM, 17.1%EM) with
      a predominance of girls without age difference. When they reached puberty after 6
      years, double the number of cases with CM was headache free. Most of the young
      changed their headache characteristics during the follow-up period independent
      from management strategies. CONCLUSIONS: Our results showed that CM is an
      important cause of headache in both children and adolescents with some defining
      headache characteristics and risk factors concentrated in different age-groups.

PMID- 22882206
TI  - Is preeclampsia a significant risk factor for long-term hospitalizations and
      morbidity?
AB  - OBJECTIVE: The present study was aimed to evaluate long-term morbidity of
      patients with hypertensive disorders of pregnancy. STUDY DESIGN: A retrospective
      cohort study was conducted, including women who gave birth between the years of
      1988 to 1998, and had a follow-up until December 2009. Data were extracted by
      linking a computerized database of hospitalizations with computerized database
      containing maternal records from the same regional medical center. The exposed
      group comprised 2072 patients with mild or severe preeclampsia in one or more of
      their pregnancies and the comparison group included 20742 patients without
      preeclampsia. Excluded from the study were patients with chronic hypertension and
      pre-gestational diabetes before the index pregnancy. Data included subsequent
      hospitalizations in internal medicine, oncology, nephrology, neurology, cardiac
      intensive care unit, and hematology, as well as a diagnosis of chronic
      hypertension during the follow-up period. RESULTS: Patients with preeclampsia had
      significantly higher rates of chronic hypertension diagnosed after the index
      pregnancy as compared with patients without preeclampsia (12.5% vs. 0.9%; OR =
      15.8, 95% CI 12.9-19.3; p < 0.001). Likewise, patients with preeclampsia were
      more likely to be hospitalized at least once (13.7% vs. 11.4%; OR = 1.2, 95% CI
      1.1-1.4; p = 0.002) as compared with patients without preeclampsia. Exposed women
      had 582 hospitalizations (0.28 hospitalization/patient), while the non-exposed
      patients had a total of 4687 hospitalizations (0.23 hospitalization/patient; p <
      0.001). CONCLUSION: Preeclampsia is a significant risk factor for long-term
      morbidity such as chronic hypertension and hospitalizations later in life.

PMID- 22882207
TI  - The incidence of prematurity or low birth weight for gestational age among
      children with dyslexia.

PMID- 22882208
TI  - Facial skin barrier function recovery after microneedle transdermal delivery
      treatment.
AB  - BACKGROUND: Microneedle treatment is currently used in the cosmetic industry for
      several skin conditions. Despite their extensive use, there is lack of sufficient
      data on the safety of microneedles. OBJECTIVE: To investigate the degree of acute
      skin damage and the time required for facial skin barrier function to recover
      using different microneedle lengths and numbers of applications. MATERIALS AND
      METHODS: Each side of a volunteer's face was randomly treated with one of the
      following treatments: five applications of 0.15-mm microneedles, five
      applications of 0.25-mm microneedles, 10 applications of 0.15-mm microneedles, or
      10 applications of 0.25-mm microneedles. Transepidermal water loss, stratum
      corneum hydration, and skin erythema were measured at baseline, immediately after
      treatment, 4 hours after treatment, and 8 hours after treatment and at 24-hour
      intervals for 3 days. RESULTS: Prompt recovery of barrier function (within 72
      hours) was observed after microneedle treatment. CONCLUSION: Microneedle
      treatment is simple and inexpensive, and the skin barrier disruption it causes
      resolves quickly. Therefore, it can serve as an effective physical method of
      enhancing transdermal delivery of medications for the treatment of many cosmetic
      and dermatological conditions.

PMID- 22882209
TI  - High serum vascular endothelial growth factor level is an adverse prognostic
      factor for high-risk diffuse large B-cell lymphoma patients treated with dose
      dense chemoimmunotherapy.
AB  - OBJECTIVES: To determine whether serum vascular endothelial growth factor (s
      VEGF) levels and VEGF gene expression in tumor tissue predict survival of diffuse
      large B-cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. METHODS:
      VEGF levels were measured in serum samples from 102 patients <65 yrs with high
      risk DLBCL using a quantitative sandwich enzyme immunoassay technique. Exon array
      data set of tumor tissues from 32 patients was concurrently used to determine
      VEGF-A exon and gene expression. All patients were treated in a Nordic phase II
      study with six dose-dense chemoimmunotherapy courses followed by systemic central
      nervous system prophylaxis. RESULTS: After a median follow-up time of 40 months,
      3-yr progression-free survival (PFS) was inferior in patients with high s-VEGF
      levels compared to those with low levels (59% vs. 83%, P = 0.005). The relative
      risk of progression or relapse was 3.1-fold (95% confidence interval 1.34-6.91, P
      = 0.008). The predictive capacity of s-VEGF levels on PFS was most pronounced in
      the DLBCLs of non-germinal center subtype. In contrast to serum data, VEGF mRNA
      expression in the lymphoma tissue did not predict outcome, and no correlation was
      found between s-VEGF levels and lymphoma VEGF expression. CONCLUSION:
      Pretreatment s-VEGF level is a predictor of PFS after chemoimmunotherapy and may
      help to further stratify high-risk DLBCL patients into low- and high-risk groups.

PMID- 22882210
TI  - The biofilm formation defect of a Bacillus subtilis flotillin-defective mutant
      involves the protease FtsH.
AB  - Biofilm formation in Bacillus subtilis requires the differentiation of a
      subpopulation of cells responsible for the production of the extracellular matrix
      that structures the biofilm. Differentiation of matrix-producing cells depends,
      among other factors, on the FloT and YqfA proteins. These proteins are present
      exclusively in functional membrane microdomains of B. subtilis and are homologous
      to the eukaryotic lipid raft-specific flotillin proteins. In the absence of FloT
      and YqfA, diverse proteins normally localized to the membrane microdomains of B.
      subtilis are not functional. Here we show that the absence of FloT and YqfA
      reduces the level of the septal-localized protease FtsH. The flotillin homologues
      FloT and YqfA are occasionally present at the midcell in exponentially growing
      cells and the absence of FloT and YqfA negatively affects FtsH concentration.
      Biochemical experiments indicate a direct interaction between FloT/YqfA and FtsH.
      Moreover, FtsH is essential for the differentiation of matrix producers and
      hence, biofilm formation. This molecular trigger of biofilm formation may
      therefore be used as a target for the design of new biofilm inhibitors.
      Accordingly, we show that the small protein SpoVM, known to bind to and inhibit
      FtsH activity, inhibits biofilm formation in B. subtilis and other distantly
      related bacteria.

PMID- 22882212
TI  - Tolerance without toxicity? alpha1-antitrypsin as a novel alternative to
      immunosuppression.

PMID- 22882211
TI  - Hyperglycemia and incidence of frailty and lower extremity mobility limitations
      in older women.
AB  - OBJECTIVES: To determine the degree to which hyperglycemia predicts the
      development of frailty and lower extremity mobility limitations. DESIGN:
      Secondary data analysis of longitudinal data collected in a prospective cohort
      study. SETTING: Baltimore, Maryland. PARTICIPANTS: Three hundred twenty-nine
      women from the Women's Health and Aging Study II aged 70 to 79 at baseline who
      had all variables needed for analysis. MEASUREMENTS: Glycosylated hemoglobin
      (HbA1c) at baseline, categorized as less than 5.5%, 5.5% to 5.9%, 6.0% to 6.4%,
      6.5% to 7.9%, and 8.0% and greater, was the independent variable. The incidence
      of frailty and lower extremity mobility limitations (based on self-reported
      walking difficulty, walking speed, and Short Performance Physical Battery score)
      was determined (follow-up ~ 9 years). Frailty was assessed using the
      Cardiovascular Health Study criteria. Covariates included demographic
      characteristics, body mass index, interleukin-6 level, and clinical history of
      comorbidities. Statistical analyses included Kaplan-Meier survival curves and Cox
      regression models adjusted for important covariates. RESULTS: In time-to-event
      analyses, HbA1c category was associated with incidence of walking difficulty (P =
      .049) and low physical performance (P = .001); association with incidence of
      frailty and low walking speed had a trend toward significance (both P = .10). In
      regression models adjusted for demographic characteristics, HbA1c of 8.0% or
      greater (vs < 5.5%) was associated with an approximately three-times greater risk
      of incident frailty and three to five times greater risk of lower extremity
      mobility limitations (all P < .05). In fully adjusted models, HbA1c of 8.0% or
      greater (vs < 5.5%) was associated with incident frailty (hazard ratio (HR) =
      3.33, 95% confidence interval (CI) = 1.24-8.93), walking difficulty (HR = 3.47,
      95% CI = 1.26-9.55), low walking speed (HR = 2.82, 95% CI = 1.19-6.71), and low
      physical performance (HR = 3.60, 95% CI = 1.52-8.53). CONCLUSION: Hyperglycemia
      is associated with the development of frailty and lower extremity mobility
      limitations in older women. Future studies should identify mediators of these
      relationships.

PMID- 22882213
TI  - CD4(+) T cells suppress immune response to cancer: novel targets for antitumor
      efforts.

PMID- 22882214
TI  - Newly discovered innate response activator B cells: crucial responders against
      microbial sepsis.

PMID- 22882216
TI  - Rituximab: emerging treatment strategies of immune-mediated glomerular disease.
AB  - The use of monoclonal antibodies in the treatment of malignancy and autoimmune
      diseases has rapidly expanded in the last decade. Rituximab, a monoclonal
      antibody to the CD20 antigen on B cells, was first approved by the US FDA in 1997
      to treat non-Hodgkin's B-cell lymphoma. It is now used, however, for a variety of
      diseases in both on- and off-label uses. It was approved by the FDA for use in
      refractory rheumatoid arthritis in 2007, and in April 2011 it was approved for
      the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides
      (including granulomatosis with polyangiitis [Wegener's granulomatosis] and
      microscopic polyangiitis), based on the promising results of the RAVE trial.
      Within the field of nephrology, in addition to its use in anti-neutrophil
      cytoplasmic antibody-associated vasculitides, it is has been used in the
      treatment of membranous nephropathy, membranoproliferative glomerulonephritis and
      lupus nephritis.

PMID- 22882217
TI  - Subcutaneous alemtuzumab for multiple sclerosis.

PMID- 22882219
TI  - Flares of systemic lupus erythematosus during pregnancy and the puerperium:
      prevention, diagnosis and management.
AB  - Systemic lupus erythematosus is a systemic autoimmune disease that primarily
      affects women in their reproductive age years. Pregnancy in systemic lupus
      erythematosus now has favorable outcomes for the majority of women. However,
      flares of disease activity, preeclampsia, fetal loss, intrauterine growth
      retardation and preterm birth are established risks of such pregnancies. Active
      lupus nephritis at the time of conception poses the greatest risk for disease
      flares and poor obstetric outcomes. Patients should delay conception until their
      lupus has been in remission for at least 6 months. In addition, certain lupus
      medications are potentially teratogenic and need to be stopped before conception.
      The signs and symptoms of a lupus flare may mimic those of normal pregnancy,
      impeding its recognition during pregnancy. Hydroxychloroquine, low-dose
      prednisone, pulse intravenous methylprednisolone and azathioprine are commonly
      used to treat lupus flares during pregnancy.

PMID- 22882218
TI  - Muscle autoantibodies in myasthenia gravis: beyond diagnosis?
AB  - Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. A
      number of molecules, including ion channels and other proteins at the
      neuromuscular junction, may be targeted by autoantibodies leading to abnormal
      neuromuscular transmission. In approximately 85% of patients, autoantibodies,
      directed against the postsynaptic nicotinic acetylcholine receptor can be
      detected in the serum and confirm the diagnosis, but in general, do not precisely
      predict the degree of weakness or response to therapy. Antibodies to the muscle
      specific tyrosine kinase are detected in approximately 50% of generalized
      myasthenia gravis patients who are seronegative for anti-acetylcholine receptor
      antibodies, and levels of anti-muscle-specific tyrosine kinase antibodies do
      appear to correlate with disease severity and treatment response. Antibodies to
      other muscle antigens may be found in the subsets of myasthenia gravis patients,
      potentially providing clinically useful diagnostic information, but their utility
      as relevant biomarkers (measures of disease state or response to treatment) is
      currently unclear.

PMID- 22882220
TI  - Current treatments of rheumatoid arthritis: from the 'NinJa' registry.
AB  - In this review, recent changes in both treatments and outcomes of rheumatoid
      arthritis (RA) in Japan were analyzed by viewing the National Database of
      Rheumatic Diseases by iR-net, one of the largest clinical databases for RA
      patients in Japan. Regarding drug therapy, the use of methotrexate has been
      continuously increasing and has established a place as an anchor drug in the
      treatment of RA among other nonbiologic disease-modifying antirheumatic drugs;
      however, the dosage used is still significantly less compared with that of
      western countries. In addition to methotrexate, the use of tacrolimus has
      increased gradually. The most prominent observed change is a rapid increase in
      the use of biologics, which rose to stardom in the treatment of RA in Japan and
      western countries. These changes in drug therapy could allow us to control RA
      disease activity more tightly. In line with this, the outcomes of patients with
      RA in Japan have been improving continuously, both clinically and functionally.
      Subsequently, the use of both NSAIDs and corticosteroids has decreased. In
      addition, overall rates of joint operations related to RA have also decreased; in
      particular, a significant decrease was noticed in the incidence of joint
      replacement and synovectomy. Overall, the trends in treatments and subsequent
      outcomes for RA in Japan have exactly followed those seen in western countries.

PMID- 22882221
TI  - T-cell receptor and carbamazepine-induced Stevens-Johnson syndrome and toxic
      epidermal necrolysis: understanding a hypersensitivity reaction.
AB  - Ample evidence exists to support the view that drug hypersensitivity is mediated
      by adaptive immunity, which involves MHC-restricted drug presentation, activation
      and clonal expansion of T cells. The specific MHC molecules implicated in
      hypersensitivity have been identified; for example, HLA-B*5701 in abacavir
      induced drug hypersensitivity and HLA-B*1502 in carbamazepine-induced Stevens
      Johnson syndrome. However, little is known about the role of drug-specific T
      cells and their T-cell receptors (TCRs) in the pathogenesis of drug
      hypersensitivity. Using the combination of a strong HLA-B*1502 predisposition in
      carbamazepine-induced Stevens-Johnson syndrome and applying global analysis of
      the TCR repertoire, restricted and common TCR usage in the development of severe
      drug hypersensitivity have recently been documented. This article reviews recent
      advances in the understanding of the pathogenic role of drug-specific T cells and
      their TCRs in the development of drug hypersensitivity and provides an analysis
      of their potential clinical implications.

PMID- 22882224
TI  - The utility of diagnostic biopsy specimens for predictive molecular testing in
      colorectal cancer.
AB  - AIMS: If stratified medicine is to be applied in the neoadjuvant setting,
      predictive testing will have to be undertaken on preoperative diagnostic biopsy
      specimens. The aim of this study was to evaluate whether a diagnostic biopsy was
      adequately representative of the main tumour in colorectal cancer. METHODS AND
      RESULTS: Thirty cases of paired biopsy and subsequent resection specimens were
      randomly selected. Samples were screened for mutation in KRAS (codons 12/13, 61,
      and 146), BRAF (codon 600 and exon 11), PIK3CA (exons 1, 9, and 20), TP53 (exons
      5-8), and microsatellite instability, using the quick multiplex consensus or
      standard polymerase chain reaction (PCR) protocols followed by high-resolution
      melting analysis. A total of 570 paired PCR tests were performed for mutation
      detection, and identical results were obtained in both biopsy and resection
      specimens in 569 tests (>99% concordance). Four cases (13%) showed microsatellite
      instability, and, in all four cases, instability was seen at identical
      mononucleotide markers in both biopsy and matched resection specimens.
      CONCLUSIONS: This is the first study to show that diagnostic biopsy specimens,
      even though they are a tiny sample of the tumour, are sufficiently representative
      for use in predictive testing for early driver mutations in colorectal cancer.

PMID- 22882225
TI  - Do dose-related mechanisms exist for the angiogenic behaviours of heparin
      derivatives?

PMID- 22882226
TI  - Understanding why patients with immune thrombocytopenia are deeply divided on
      splenectomy.
AB  - BACKGROUND: Splenectomy is an effective treatment for chronic immune
      thrombocytopenia (ITP); however, patients' willingness to accept splenectomy is
      variable. OBJECTIVE: To explore why some ITP patients accepted splenectomy when
      recommended by their physician while others refused. DESIGN: Qualitative
      descriptive study using one-to-one, in-depth patient interviews and a team-based
      approach to thematic analysis. RESULTS: Of 25 patients interviewed, 15 refused
      splenectomy and 10 accepted and were awaiting surgery. Themes about the
      influences on splenectomy decision making that emerged from patient interviews
      were (i) the perceived impact of ITP on quality of life, (ii) patients' view of
      splenectomy as a last resort treatment, (iii) patients' interpretations of the
      rates of treatment success and failure and (iv) a perceived lack of familiarity
      about ITP. Patients who accepted splenectomy perceived their disease as having a
      negative impact on their quality of life, whereas patients who refused felt their
      situation was not severe enough to warrant surgery. Patients developed their own
      experiential interpretations of the success rates of splenectomy quoted to them.
      A general lack of awareness of the clinical impact of ITP and its cause was
      identified by patients as barriers to choosing splenectomy. CONCLUSIONS:
      Patients' disease experience, perceptions of the lack of treatment alternatives,
      interpretations of treatment success and failure rates and a general lack of
      awareness about ITP influenced treatment choice. This study represents a first
      step towards contextualizing treatment decision making in ITP, focusing on
      patient preferences and values.

PMID- 22882222
TI  - Photodynamic therapy induces an immune response against a bacterial pathogen.
AB  - Photodynamic therapy (PDT) employs the triple combination of photosensitizers,
      visible light and ambient oxygen. When PDT is used for cancer, it has been
      observed that both arms of the host immune system (innate and adaptive) are
      activated. When PDT is used for infectious disease, however, it has been assumed
      that the direct antimicrobial PDT effect dominates. Murine arthritis caused by
      methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT
      with intravenously injected Photofrin((r)). PDT with intra-articular Photofrin
      produced a biphasic dose response that killed bacteria without destroying host
      neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria
      while preserving neutrophils. We used bioluminescence imaging to noninvasively
      monitor murine bacterial arthritis and found that PDT with intra-articular
      methylene blue was not only effective, but when used before infection, could
      protect the mice against a subsequent bacterial challenge. The data emphasize the
      importance of considering the host immune response in PDT for infectious disease.

PMID- 22882227
TI  - Patterns of shoot architecture in locally adapted populations are linked to
      intraspecific differences in gene regulation.
AB  - * Shoot architecture, including the number and location of branches, is a crucial
      aspect of plant function, morphological diversification, life history evolution
      and crop domestication. * Genes controlling shoot architecture are well
      characterized in, and largely conserved across, model flowering plant species.
      The role of these genes in the evolution of morphological diversity in natural
      populations, however, has not been explored. * We identify axillary meristem
      outgrowth as a primary driver of divergent branch number and life histories in
      two locally adapted populations of the monkeyflower, Mimulus guttatus. *
      Furthermore, we show that MORE AXILLARY GROWTH (MAX) gene expression strongly
      correlates with natural variation in branch outgrowth in this species, linking
      modification of the MAX-dependent pathway to the evolutionary diversification of
      shoot architecture.

PMID- 22882228
TI  - Rampant host- and defensive phenotype-associated diversification in a goldenrod
      gall midge.
AB  - Natural selection can play an important role in the genetic divergence of
      populations and their subsequent speciation. Such adaptive diversification, or
      ecological speciation, might underlie the enormous diversity of plant-feeding
      insects that frequently experience strong selection pressures associated with
      host plant use as well as from natural enemies. This view is supported by
      increasing documentation of host-associated (genetic) differentiation in
      populations of plant-feeding insects using alternate hosts. Here, we examine
      evolutionary diversification in a single nominal taxon, the gall midge Asteromyia
      carbonifera (O.S.), with respect to host plant use and gall phenotype. Because
      galls can be viewed as extended defensive phenotypes of the midges, gall
      morphology is likely to be a reflection of selective pressures by enemies. Using
      phylogenetic and comparative analyses of mtDNA and nuclear sequence data, we find
      evidence that A. carbonifera populations are rapidly diversifying along host
      plant and gall morphological lines. At a broad scale, geography explains
      surprisingly little genetic variation, and there is little evidence of strict co
      cladogenesis with their Solidago hosts. Gall morphology is relatively labile,
      distinct gall morphs have evolved repeatedly and colonized multiple hosts, and
      multiple genetically and morphologically distinct morphs frequently coexist on a
      single host plant species. These results suggest that Asteromyia carbonifera is
      in the midst of an adaptive radiation driven by multitrophic selective pressures.
      Similar complex community pressures are likely to play a role in the
      diversification of other herbivorous insect groups.

PMID- 22882229
TI  - Influence of clinical experience on the radiographic determination of endodontic
      working length.
AB  - AIM: To determine the influence of clinical experience on the accuracy and
      consistency of estimation of radiographic working length (WL) for the root canal
      treatment of single-rooted teeth. METHODOLOGY: Forty conventional WL periapical
      radiographs that included variations in file length were selected. They were
      digitally scanned and arranged in PowerPoint presentations on CDs. These were
      distributed to three assessor groups; fourth-year undergraduates at two stages of
      training (Groups 1 and 2) and endodontic postgraduates (Group 3). Participants
      were asked to determine the adjustment needed in millimetres to position the file
      tip at the correct WL for each image. A gold standard file position was provided
      by three experienced endodontists. For inter-group comparison of scores, the
      Kruskal-Wallis, ANOVA and post hoc Bonferroni tests were used. Evaluation of
      intra-examiner consistency was with the Kappa test. To evaluate intra-group
      consistency, the Wilcoxon signed rank test was used to compare the frequency of
      weighted correct scorings. RESULTS: File adjustments of Group 3 were
      significantly more accurate than those of Group 1 (P = 0.006). The scores of
      Group 3 were also better than those of Group 2, although the difference was not
      significant. When the scores of the undergraduate groups were compared, the
      difference was not statistically significant. The consistency of the groups was
      not affected by a 2-week pause between assessments, and no definite pattern could
      be detected across any of the groups with the Kappa test. CONCLUSION: Clinical
      experience after graduation influenced the accuracy of estimating the adjustments
      needed for correct radiographic WL of single-rooted teeth. The most experienced
      group was significantly more accurate than the other groups.

PMID- 22882230
TI  - A comparative study at two different altitudes with two dietary nutrition levels
      on rumen fermentation and energy metabolism in Chinese Holstein cows.
AB  - The object of this study was to investigate the effect of two altitudes (1600 vs.
      3600 m) with two nutritional levels [5.88 MJ/kg dry matter (DM) vs. 7.56 MJ/kg
      DM] on apparent total tract digestibility, rumen fermentation, energy metabolism,
      milk yield and milk composition in Chinese Holstein cows. Sixteen Chinese
      Holstein cows in their third lactation with close body weights, days in milk and
      milk yield were randomly divided into four groups, of which two were directly
      transferred from Lanzhou (altitude of 1600 m) to Lhasa (altitude of 3600 m). Four
      treatments (high plateau and high nutrition level, HA-HN; high plateau and low
      nutrition level, HA-LN; low plateau and high nutrition level, LA-HN; and low
      plateau and low nutrition level, LA-LN) were randomly arranged in a 2 * 2
      factorial experimental design. Results indicated that the apparent total tract
      digestibility of a diet's DM, organic matter, crude protein, neutral detergent
      fibre and acid detergent fibre and DM intake were not affected by either altitude
      or nutrition level (p > 0.05). Milk protein percentage was higher for the diet
      with the high level of nutrition than for the diet with low nutrition level
      irrespective of altitude (p < 0.05). Percentages of milk fat and milk lactose
      were not affected by either altitude or nutrition level (p > 0.05). The
      metabolizable energy used for milk energy output was decreased by high altitude
      in comparison with that at low altitude (p < 0.05). No differences were observed
      in the live body weight or body condition score (BCS) of Chinese Holstein cows
      among all of the four treatments (p > 0.05). 

PMID- 22882231
TI  - EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections
      of the nervous system.
AB  - BACKGROUND: Polymerase chain reaction (PCR) as a means to amplify nucleic acids
      has become an essential element in diagnosis of infections. It has evolved into a
      simple and rapid, easy- to- use approach. At present there are no published
      guidelines for the usage of PCR technology for the diagnosis of infections of the
      nervous system. METHODS: We reviewed the advantages and pitfalls of PCR in order
      to guide neurologists and infectious diseases experts in its application for the
      diagnosis of infections of the nervous system. Medical reference systems were
      searched, and original papers, meta-analyses, review papers, book chapters and
      guidelines recommendations were reviewed. The final literature search was
      performed in May 2012. Recommendations were reached by consensus.
      RECOMMENDATIONS: The reliability of PCR technology for the diagnosis of
      neurological infections is currently based on the pathogens. The main
      contribution of PCR is to the diagnosis of viral infections followed by bacterial
      CNS infections with the notable exception of tuberculous meningitis. Efficacy for
      the diagnosis of protozoal infections and helminthic infestations has also been
      established in many instances. Unfortunately, current molecular PCR technology is
      far from becoming routine in resource-poor countries where such infections are
      prevalent. Despite the importance of fungal infections in the context of the
      immune-compromised host, there is not enough data to recommend the routine use of
      PCR. CONCLUSIONS: PCR technology is currently a reliable method for the diagnosis
      of viral and bacterial (except tuberculosis) infections, and only for some
      protozoal infections and helminthic infestations.

PMID- 22882232
TI  - Morphology-driven high-performance polymeric photodetector.
AB  - The influence of polymer/fullerene morphology on photodetector performance is
      reported. Various morphologies of spin-coated films are generated by different
      blending ratio. Morphological study combined with measurement of charge carrier
      mobility reveals that blend films with an excess content of crystalline fullerene
      have a phase-separated morphology, resulting in enhanced charge carrier mobility.
      Under this phase separated morphology, photovoltaic performance is enhanced
      because of the generation of percolating pathways for charge carriers.
      Interestingly, however, a homogeneous morphology is found to be more beneficial
      for photodetector application than this phase separated morphology. An optimized
      device displayed 3 dB bandwidth up to 1 kHz and detectivities up to D = 1.1 *
      10(10) cm Hz(1/2) W(-1). These results emphasize the importance of developing an
      independent strategy for designing high performance photodetectors separately
      from solar cell devices both in terms of materials and device geometry. Possible
      relations between morphology and various figures of merit of photodetectors are
      discussed.

PMID- 22882233
TI  - Prevalence of ADHD symptoms in patients with congenital heart disease.
AB  - OBJECTIVE: The presence of attention-deficit-hyperactivity disorder (ADHD)
      symptoms in children with congenital heart disease (CHD) was investigated.
      METHODS: Swanson, Nolan and Pelham teacher and parent rating scales, version 4
      (SNAP-IV), commonly used for assessing symptoms of ADHD, were completed by
      parents and counselors of children who attended a CHD summer camp. Mean scores (n
      = 51) were compared with two comparison groups without CHD: patients with ADHD (n
      = 75) and patients without ADHD (n = 41). Parent scores were also compared to
      previously published parent normative data. RESULTS: Patients with CHD were
      reported to have elevated SNAP-IV scores by parents and counselors (11.8%).
      Parent ratings of inattention were significantly greater in CHD subjects when
      compared to the comparison group without ADHD (P < 0.001), and similar to the
      ADHD-positive comparison group. Regarding parent ratings of hyperactivity and
      impulsivity, the CHD group was significantly lower than the ADHD-positive
      controls (P = 0.024) but greater than the ADHD-negative controls (P < 0.001).
      CONCLUSION: ADHD symptoms are more prevalent in children with CHD. Parent ratings
      of inattention and hyperactivity symptoms in CHD patients are similar to ratings
      in children diagnosed with ADHD. There is a trend towards a greater prevalence of
      inattention symptoms in patients with cyanosis or single ventricle physiology.

PMID- 22882235
TI  - Pregnancy-associated acquired arteriovenous malformation of the nail unit: a
      novel cause of localized erythronychia.
AB  - Localized longitudinal erythronychia describes a solitary red streak limited to a
      single nail unit. Localized longitudinal erythronychia can be caused by both
      benign and malignant entities. Most commonly, the cause is a benign process, such
      as an onychopapilloma. We report a case of an acquired subungual arteriovenous
      malformation that presented as localized longitudinal erythronychia during
      pregnancy. To our knowledge, this is the first report of localized longitudinal
      erythronychia arising from a pregnancy-associated arteriovenous malformation of
      the nail unit.

PMID- 22882234
TI  - Loss of CD26 protease activity in recipient mice during hematopoietic stem cell
      transplantation results in improved transplant efficiency.
AB  - BACKGROUND: A firm understanding of the biology of hematopoietic stem and
      progenitor cell (HSC/HPC) trafficking is critical to improve transplant
      efficiency and immune reconstitution during hematopoietic stem cell
      transplantation (HSCT). Our earlier findings suggested that suppression of CD26
      (dipeptidyl peptidase IV) proteolytic activity in the donor cell population can
      be utilized as a method for increasing transplant efficiency. However, factors in
      the recipient should not be overlooked, given the potential for the bone marrow
      (BM) microenvironment to regulate HSCT. STUDY DESIGN AND METHODS: We first
      evaluated CD26 expression and then investigated the effects of the CD26 inhibitor
      diprotin A and the absence of CD26 (CD26-/-) in recipient mice on HSC/HPC homing
      and engraftment using an in vivo congenic mouse model of HSCT. RESULTS: A
      significant increase in donor cell engraftment into the peripheral blood (PB),
      and to a lesser extent homing into the BM, was observed in CD26-/- mice or CD26
      inhibitor-treated mice. Increased PB engraftment of CD26-/- mice was significant
      at 3 and 6 months, but not 1 month, after transplant. It was noted that the
      increased homing was statistically greater with donor cell manipulation (CD26-/-
      donor cells) than with recipient manipulation (CD26-/- recipient mice).
      Conversely, donor and recipient manipulation both worked well to increase PB
      engraftment at 6 months. CONCLUSION: These results provide preclinical evidence
      of CD26, in the HSCT recipient, as a major regulator of HSC/HPC engraftment with
      minor effects on HSC/HPC homing and suggest the potential use of CD26 inhibitors
      in HSCT patients to improve transplant efficiency.

PMID- 22882236
TI  - The walk is never random: subtle landscape effects shape gene flow in a
      continuous white-tailed deer population in the Midwestern United States.
AB  - One of the pervasive challenges in landscape genetics is detecting gene flow
      patterns within continuous populations of highly mobile wildlife. Understanding
      population genetic structure within a continuous population can give insights
      into social structure, movement across the landscape and contact between
      populations, which influence ecological interactions, reproductive dynamics or
      pathogen transmission. We investigated the genetic structure of a large
      population of deer spanning the area of Wisconsin and Illinois, USA, affected by
      chronic wasting disease. We combined multiscale investigation, landscape genetic
      techniques and spatial statistical modelling to address the complex questions of
      landscape factors influencing population structure. We sampled over 2000 deer and
      used spatial autocorrelation and a spatial principal components analysis to
      describe the population genetic structure. We evaluated landscape effects on this
      pattern using a spatial autoregressive model within a model selection framework
      to test alternative hypotheses about gene flow. We found high levels of genetic
      connectivity, with gradients of variation across the large continuous population
      of white-tailed deer. At the fine scale, spatial clustering of related animals
      was correlated with the amount and arrangement of forested habitat. At the
      broader scale, impediments to dispersal were important to shaping genetic
      connectivity within the population. We found significant barrier effects of
      individual state and interstate highways and rivers. Our results offer an
      important understanding of deer biology and movement that will help inform the
      management of this species in an area where overabundance and disease spread are
      primary concerns.

PMID- 22882237
TI  - Memory traces for tonal language words revealed by auditory event-related
      potentials.
AB  - In tonal languages such as Mandarin Chinese, suprasegmental tones are used to
      signal word meaning besides consonants and vowels. To reveal memory traces for
      tonal language words, we presented native Mandarin Chinese speakers with a
      sequence of spoken syllables as standards and disyllables as deviants in a
      passive oddball paradigm. The second syllable of each disyllable carried critical
      tonal information that would define the disyllable either as a meaningful word or
      as a meaningless pseudoword. The words and pseudowords were acoustically and
      phonologically matched as well as counterbalanced. The auditory event-related
      potential in response to words was more negatively deflected than that in
      response to pseudowords. This effect was most prominent 164 ms after the word
      recognition point. Our study indicates an activation of memory traces for tonal
      language words.

PMID- 22882238
TI  - Bacterial community profiles in low microbial abundance sponges.
AB  - It has long been recognized that sponges differ in the abundance of associated
      microorganisms, and they are therefore termed either 'low microbial abundance'
      (LMA) or 'high microbial abundance' (HMA) sponges. Many previous studies
      concentrated on the dense microbial communities in HMA sponges, whereas little is
      known about microorganisms in LMA sponges. Here, two LMA sponges from the Red
      Sea, two from the Caribbean and one from the South Pacific were investigated.
      With up to only five bacterial phyla per sponge, all LMA sponges showed lower
      phylum-level diversity than typical HMA sponges. Interestingly, each LMA sponge
      was dominated by a large clade within either Cyanobacteria or different classes
      of Proteobacteria. The overall similarity of bacterial communities among LMA
      sponges determined by operational taxonomic unit and UniFrac analysis was low.
      Also the number of sponge-specific clusters, which indicate bacteria specifically
      associated with sponges and which are numerous in HMA sponges, was low. A
      biogeographical or host-dependent distribution pattern was not observed. In
      conclusion, bacterial community profiles of LMA sponges are clearly different
      from profiles of HMA sponges and, remarkably, each LMA sponge seems to harbour
      its own unique bacterial community.

PMID- 22882239
TI  - An easy schedule for postsurgical radioiodine administration in newly diagnosed
      differentiated thyroid carcinoma patients.
AB  - OBJECTIVE: To validate the simplest approach to preparing patients with
      differentiated thyroid carcinoma (DTC) for (131) I-administration ((131) I-A),
      minimizing the impact of hypothyroidism. DESIGN: Panel study. PATIENTS: Ninety
      patients with DTC were enrolled in the study. Sixty (Group A) underwent total
      thyroidectomy (TT); L-T4 was not administered in preparation for (131) I-A
      planned for 3 weeks later. Thirty patients (Group B) with previous TT and (131) I
      A stopped L-T4 in preparation for clinical evaluation, including whole-body
      scanning (WBS)/radioiodine therapy during thyrotrophin (TSH) stimulation planned
      for 3 weeks (or more) later. MEASUREMENTS: Thyrotrophin was measured the day
      before TT for group A, during L-T4 for group B (baseline-time 1) and then every
      week until it reached >= 30 mIU/l (time 2). Quality of life (QoL) was evaluated
      by Billewicz index. RESULTS: At week 3, 100% of patients in group A and 56.6% of
      group B exceeded TSH > 30 mIU/l. In group B, the cut-off was achieved in four
      patients at the fourth week (TSH 38.6 +/- 8.7 mIU/l), in 3 at the fifth (53.2 +/-
      3) and in 6 at the sixth (42.3 +/- 6.1). From time 1 to time 2, total QoL scores
      were less affected in group A (percentage decrease: 105%) than in group B (218%).
      At time 2, the total score was >+19 in group A in 46 patients and in 30 in group
      B. In group A, TSH levels in the higher tertile of QoL (61 +/- 6 mIU/l) were not
      different from those in the lower tertile (62.3 +/- 11.1)(P > 0.1); similar
      results were seen in group B (69.3 +/- 13.3 vs 62.9 +/- 13.1)(P > 0.1). There was
      a positive correlation between the time to obtain TSH >= 30 mIU/l and total QoL
      scores. CONCLUSIONS: Quality of life scores were not affected by thyrotrophin was
      measured the day before TT levels as absolute values. A longer time to obtain TSH
      >= 30 mIU/l was positively correlated with worse scores of QoL. We suggest 3
      weeks without therapy can be used as an easy schedule in patients who undergo TT
      for DTC.

PMID- 22882240
TI  - Uterine balloon tamponade for the treatment of postpartum haemorrhage in resource
      poor settings: a systematic review.
AB  - BACKGROUND: Effective interventions addressing postpartum haemorrhage (PPH) are
      critically needed to reduce maternal mortality worldwide. Uterine balloon
      tamponade (UBT) has been shown to be an effective technique to treat PPH in
      developed countries, but has not been examined in resource-poor settings.
      OBJECTIVES: This literature review examines the effectiveness of UBT for the
      treatment and management of PPH in resource-poor settings. SEARCH STRATEGY:
      Publications were sought through searches of five electronic databases: Medline,
      Cochrane Reference Libraries, CINAHL (Cumulative Index to Nursing and Allied
      Health Literature), Embase and Popline. SELECTION CRITERIA: Titles and abstracts
      were screened for eligibility by two independent reviewers. Each reviewer
      evaluated the full text of potentially eligible articles by defined inclusion
      criteria, including the presentation of empirical data and use of UBT in resource
      poor settings to treat PPH. DATA COLLECTION AND ANALYSIS: Full text of all
      eligible publications was collected and systematically coded. MAIN RESULTS: The
      search identified 13 studies that met the inclusion criteria: six case reports or
      case series, five prospective studies and two retrospective studies for a total
      of 241 women. No randomised controlled trials were identified. The studies used
      various types of UBT, including condom catheter (n = 193), Foley catheter (n = 5)
      and Sengstaken-Blakemore oesophageal tube (n = 1). In these studies, primarily
      conducted in tertiary-care settings rather than lower-level health facilities,
      UBT successfully treated PPH in 234 out of 241 women. CONCLUSIONS: UBT is an
      effective treatment for PPH in resource-poor settings. Further study of UBT
      interventions is necessary to better understand the barriers to successful
      implementation and use in these settings.

PMID- 22882241
TI  - The need for mechanism-based medicine in neuromodulation.

PMID- 22882242
TI  - Neurotech report.

PMID- 22882243
TI  - Bench to clinical translational applications of noninvasive brain stimulation.

PMID- 22882244
TI  - Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain
      injury.
AB  - OBJECTIVE: To review the use of noninvasive brain stimulation (NBS) as a
      therapeutic tool to enhance neuroplasticity following traumatic brain injury
      (TBI). MATERIALS AND METHODS: Based on a literature search, we describe the
      pathophysiological events following TBI and the rationale for the use of
      transcranial magnetic stimulation (TMS) and transcranial direct current
      stimulation (tDCS) in this setting. RESULTS: The pathophysiological mechanisms
      occurring after TBI vary across time and therefore require differential
      interventions. Theoretically, given the neurophysiological effects of both TMS
      and tDCS, these tools may: 1) decrease cortical hyperexcitability acutely after
      TBI; 2) modulate long-term synaptic plasticity as to avoid maladaptive
      consequences; and 3) combined with physical and behavioral therapy, facilitate
      cortical reorganization and consolidation of learning in specific neural
      networks. All of these interventions may help decrease the burden of disabling
      sequelae after brain injury. CONCLUSIONS: Evidence from animal and human studies
      reveals the potential benefit of NBS in decreasing the extent of injury and
      enhancing plastic changes to facilitate learning and recovery of function in
      lesioned neural tissue. However, this evidence is mainly theoretical at this
      point. Given safety constraints, studies in TBI patients are necessary to address
      the role of NBS in this condition as well as to further elucidate its therapeutic
      effects and define optimal stimulation parameters.

PMID- 22882246
TI  - Drug-induced QT interval prolongation: does ethnicity of the thorough QT study
      population matter?
AB  - Inter-ethnic differences in drug responses have been well documented. Drug
      induced QT interval prolongation is a major safety concern and therefore,
      regulatory authorities recommend a clinical thorough QT study (TQT) to
      investigate new drugs for their QT-prolonging potential. A positive study,
      determined by breach of a preset regulatory threshold, significantly influences
      late phase clinical trials by requiring intense ECG monitoring. A few studies
      that are currently available, although not statistically conclusive at present,
      question the assumption that ethnicity of the study population may not influence
      the outcome of a TQT study. Collective consideration of available pharmacogenetic
      and clinical information suggests that there may be inter-ethnic differences in
      QT-prolonging effects of drugs and that Caucasians may be more sensitive than
      other populations. The information also suggest s that (a) these differences may
      depend on the QT-prolonging potency of the drug and (b) exposure-response (E-R)
      analysis may be more sensitive than simple changes in QT(c) interval in unmasking
      this difference. If the QT response in Caucasians is generally found to be more
      intense than in non-Caucasians, there may be significant regulatory implications
      for domestic acceptance of data from a TQT study conducted in foreign
      populations. However, each drug will warrant an individual consideration when
      extrapolating the results of a TQT study from one ethnic population to another
      and the ultimate clinical relevance of any difference. Further adequately
      designed and powered studies, investigating the pharmacologic properties and E-R
      relationships of additional drugs with different potencies, are needed in
      Caucasians, Oriental/Asian and African populations before firm conclusions can be
      drawn.

PMID- 22882247
TI  - News on microenvironmental physioxia to revisit skin cell targeting approaches.
AB  - The skin is a multifunctional organ and a first line of defense actively
      protecting from environmental stress caused by injury, microbial treat, UV
      irradiation and environmental toxins. Diverse cutaneous cell types together with
      extracellular matrix elements and factors create a dynamic scene for cellular
      communication crucial in vital processes such as wound healing, inflammation,
      angiogenesis, immune response. Direct functional success of skin equilibrium
      depends on its microenvironment settings and particularly the local oxygen
      tension. Indeed, skin entire milieu is characterized by and highly dependent on
      its low oxygen tension called physioxia as emphasized in this review. In the
      context of skin physioxia, we review and propose here new approaches to minimize
      age-related changes in skin state and function. We particularly emphasize
      carbohydrate-mediated interactions and new 3D models of engineered skin
      substitutes. We highlight newly emerged tools and targets including stem cells,
      miRNAs, matrix metalloproteinases, mitochondria and natural antioxidants that are
      promising in prevention of skin ageing and disease restraint. In the era of
      advanced dermatology, new attempts are bringing us closer to 'well being'
      perception.

PMID- 22882248
TI  - Rotavirus vaccination: a concise review.
AB  - Live attenuated oral rotavirus vaccines were tested for proof-of-concept in the
      early 1980s, the first vaccine (RotaShield, Wyeth) was introduced in 1998 but was
      subsequently withdrawn because of association with intussusception, and the two
      currently licensed vaccine (Rotarix, GlaxoSmithKline, and RotaTeq, Merck) were
      introduced in 2006. Before licensure both vaccines were extensively tested for
      safety (for intussusception) and efficacy in trials comprising in over 60,000
      infants each. Rotarix is a single-strain human rotavirus vaccine (RV1) and
      RotaTeq is a combination of five bovine-human reassortant rotaviruses (RV5).
      Although the composition of the two vaccines is different, their field
      effectiveness and, largely, mechanism of action are similar. Both prevent
      effectively severe rotavirus gastroenteritis (RVGE) but are less efficacious
      against mild RVGE or rotavirus infection. Field effectiveness of these vaccines
      in Europe and the USA against severe RVGE has been above 90% and in Latin America
      around 80%. Trials in Africa have yielded efficacy rates between 50 and 80%.
      Rotavirus vaccination has been introduced into the national immunization
      programmes of about 20 countries in Latin America, with Brazil and Mexico as
      leading countries, as well as in the USA, Australia and South Africa.
      Introduction into other African countries will start in 2012. In Europe, Belgium,
      Luxembourg, Austria and Finland and five federal states of Germany have
      introduced universal rotavirus vaccination. The reasons for the slow progress in
      Europe include low mortality from RVGE, unfavourable cost-benefit calculations in
      some countries, and concerns that still exist over intussusception.

PMID- 22882249
TI  - Insulin aspart has a shorter duration of action than human insulin over a wide
      dose-range.
AB  - AIMS: Regular human insulin (RHI) at high doses shows prolongation of its
      duration of action potentially leading to late postprandial hypoglycaemia. This
      study compared late metabolic activity (4-12 and 6-12 h post-dosing) and duration
      of action (time to reach late half-maximal activity) over a range of doses
      between insulin aspart (IAsp) and RHI. METHODS: Pharmacokinetic and
      pharmacodynamic properties of subcutaneous IAsp and RHI (6, 12 and 24 (I)U) were
      compared in 16 healthy subjects in this double-blind, randomized, six-way
      crossover glucose clamp study. RESULTS: With increasing doses of both insulins,
      metabolic activity, insulin exposure, maximum metabolic effect and maximum serum
      insulin concentration increased linearly. Late metabolic activity was lower for
      IAsp than RHI at all doses, reaching statistical significance (p < 0.05) for 12
      and 24 (I)U. Likewise, IAsp had a shorter duration of action at all doses (p <
      0.01) and reached time to 80% of total metabolic activity earlier at doses of 12
      and 24 (I)U (p < 0.05). IAsp, compared with RHI, showed a higher maximum
      metabolic effect at 12 and 24 (I)U (p < 0.0001) and a stronger early metabolic
      activity for all three doses (p < 0.05). CONCLUSIONS: IAsp showed a shorter
      duration of action and, particularly with doses of 12 and 24 (I)U, less late
      metabolic activity than RHI. These properties might contribute to the lower
      incidence of hypoglycaemia observed with IAsp versus RHI in clinical trials as
      lower late metabolic activity should decrease the risk of late postprandial
      hypoglycaemia.

PMID- 22882250
TI  - Prurigo even as a symptom of a linear IgA bullous disease.

PMID- 22882251
TI  - The dynamics of analogue signalling in local networks controlling limb movement.
AB  - Communication by analogue signals is relatively common in arthropod local
      networks. In the locust, non-spiking local interneurons play a key role in
      controlling sets of motor neurons in the generation of local reflex movements of
      the limbs. Here, our aim was two-fold. Our first aim was to determine the coding
      properties of a subpopulation of these interneurons by using system
      identification approaches. To this end, the femoro-tibial chordotonal organ,
      which monitors the movements of the tibia about the femur, was stimulated with
      Gaussian white noise and with more natural stimuli corresponding to the movements
      of the tibia during walking. The results showed that the sample of interneurons
      analysed displayed a wide, and overlapping, range of response characteristics.
      The second aim was to develop and test improved data analysis methods for
      describing neuronal function that are more robust and allow statistical analysis,
      a need emphasized by the high levels of background neuronal activity usually
      observed. We found that nonlinear models provided an improved fit in describing
      the response properties of interneurons that were then classified with
      statistical clustering methods. We identified four distinct categories of
      interneuron response that can be further divided into nine groups, with most
      interneurons being excited during extension movements of the leg, reflecting the
      outputs of upstream spiking local interneurons.

PMID- 22882252
TI  - Photophysical probes to assess the potential of cholic acid aggregates as drug
      carriers.
AB  - The two enantiomers of the nonsteroidal antiinflammatory drug naproxen and of its
      methyl ester have been selected as representative probes with markedly different
      hydrophobicity to assess the potential of cholic acid aggregates as drug carriers
      by means of photophysical techniques. The different distribution of the probes
      between bulk solution and aggregates has been assessed by quenching of their
      singlet and triplet excited states by iodide and nitrite anions, respectively.
      This straightforward photophysical methodology can, in principle, be extended to
      a variety of drugs containing a photoactive chromophore. 

PMID- 22882253
TI  - Metabolic activation of the HOG MAP kinase pathway by Snf1/AMPK regulates lipid
      signaling at the Golgi.
AB  - Phosphatidylinositol-4-phosphate (PI(4)P) is an important regulator of Golgi
      function. Metabolic regulation of Golgi PI(4)P requires the lipid phosphatase
      Sac1 that translocates between endoplasmic reticulum (ER) and Golgi membranes.
      Localization of Sac1 responds to changes in glucose levels, yet the upstream
      signaling pathways that regulate Sac1 traffic are unknown. Here, we report that
      mitogen-activated protein kinase (MAPK) Hog1 transmits glucose signals to the
      Golgi and regulates localization of Sac1. We find that Hog1 is rapidly activated
      by both glucose starvation and glucose stimulation, which is independent of the
      well-characterized response to osmotic stress but requires the upstream element
      Ssk1 and is controlled by Snf1, the yeast homolog of AMP-activated kinase (AMPK).
      Elimination of either Hog1 or Snf1 slows glucose-induced translocation of Sac1
      lipid phosphatase from the Golgi to the ER and thus delays PI(4)P accumulation at
      the Golgi. We conclude that a novel cross-talk between the HOG pathway and
      Snf1/AMPK is required for the metabolic control of lipid signaling at the Golgi.

PMID- 22882254
TI  - Expression and electrophysiological characteristics of P2X3 receptors in
      interstitial cells of Cajal in rats with partial bladder outlet obstruction.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In the urinary
      bladder, histological studies suggest a network of functionally connected
      interstitial cells of Cajal (ICCs) are located between the urothelium and sensory
      nerve endings, which might transfer signals directly between them. Purinergic
      P2X3 receptors may play roles in the micturition reflex pathway, and its
      expression profiles in ICCs could be altered in urinary bladder dysfunction. The
      present experiments showed a novel time-dependent P2X3 receptor up-regulation in
      ICCs in an experimental rat model of partial bladder outlet obstruction.
      OBJECTIVE: To investigate the expression and electrophysiological characteristics
      of purinergic P2X3 receptors in interstitial cells of Cajal (ICCs) at different
      time points after partial bladder outlet obstruction (PBOO) in rats. MATERIALS
      AND METHODS: In all, 48 female Sprague-Dawley rats were randomly divided into
      four groups: 4, 6 and 8 week PBOO groups and sham-operated controls. At 4 weeks
      after surgery, cystometry was performed to investigate bladder function in vivo.
      Subsequently, the rats were humanely killed at 4, 6 or 8 weeks and the bladders
      were harvested for measurements. P2X3 expression in ICCs of bladder was
      investigated by immunofluorescent staining. The level of P2X3 mRNA was detected
      by reverse transcription-polymerase chain reaction (RT-PCR). Inward currents in
      corresponding ICCs after PBOO were investigated electrophysiologically. RESULTS:
      Cystometrography showed a valid increase in maximum detrusor pressure in rats
      subjected to PBOO. The bladder weight in the PBOO group was significantly higher
      than that in the control group. In contrast to sham rats, there was a significant
      increase in the intensity of P2X3 staining in the ICCs in all PBOO groups. C-kit
      labelled isolated ICCs were strongly stained with the P2X3 antibody. RT-PCR
      showed that the expression of P2X3 mRNA was significantly up-regulated at 4, 6
      and 8 weeks in the ICCs from the PBOO rats. In the ICCs, the mean peak amplitude
      of inward currents was significantly increased in the PBOO groups compared with
      the control group. CONCLUSIONS: The expression of P2X3 receptors showed a time
      dependent up-regulation in the ICCs of the bladder in rats with PBOO. PBOO
      induced the potentiation of P2X3 receptors function, as evidenced by alpha, beta
      methylene ATP-enhanced inward currents in the ICCs of the rat bladder.

PMID- 22882255
TI  - Talking about sex as part of our role: making and sustaining practice change.
AB  - Sexual issues are common for consumers of mental health services and have many
      adverse consequences for quality of life as well as impacting negatively on the
      mental illness itself. Nurses in mental health settings are well placed to assess
      for the presence of and provide interventions for sexual concerns. To date,
      little research has been undertaken to explore nurses' attitudes and whether
      sexual issues would be accepted as part of their care. This paper presents
      findings from the third stage of a qualitative, exploratory research study with
      mental health nurses working in an Australian mental health service. The findings
      from the first two stages suggested that the participants had tended to avoid
      discussion of sexual issues, but a brief education intervention had produced a
      greater willingness to address sexual issues as part of care. The aim of the
      third stage was to determine the degree to which changes in practice had
      continued over time. Two main themes that emerged from this data were: (i)
      holism, from rhetoric to reality; and (ii) part of what I do. Addressing sexual
      issues became part of practice, a change sustained 2 years following the
      intervention, because participants recognized its importance for holistic nursing
      care.

PMID- 22882256
TI  - A novel RNASEH2B splice site mutation responsible for Aicardi-Goutieres syndrome
      in the Faroe Islands.
AB  - AIM: The aim of the study was to identify the genetic background for Aicardi
      Goutieres syndrome (AGS) in the Faroe Islands. METHODS: Four patients with AGS
      were identified. The patients had a variable phenotype, from a severe prenatal
      form with intrauterine foetal death to a milder phenotype, albeit still with an
      early onset, within the first 2-3 months. RESULTS: A genome-wide search for
      homozygosity revealed one single 15.6 Mb region of homozygosity on chromosome 13,
      which included RNASEH2B, where a splice site mutation c.322-3C>G was identified.
      Screening of 170 anonymous Faroese controls revealed a carrier frequency of
      approximately 1.8%, corresponding to an incidence of AGS in the Faroe Islands of
      around 1 in 12,300. CONCLUSION: The previously identified RNASEH2B mutations
      comprise altogether 20 mutations (missense, nonsense and splice site) with all
      patients harbouring at least one missense mutation. The severe phenotype of the
      Faroese patients compared with the previously reported patients with RNASEH2B
      mutations may be caused by the presence of two null alleles (although some
      residual normal splicing cannot be ruled out), whereas patients with one or two
      missense mutations may have some, albeit abnormal, RNASEH2B proteins, and hence
      some residual activity of RNASEH2B, explaining their milder phenotype.

PMID- 22882257
TI  - Thymosin beta4 is a novel potential prognostic marker in gastrointestinal stromal
      tumors.
AB  - Thymosin beta-4 (Tbeta(4)) is a major actin-sequestering molecule that
      contributes to cell growth, differentiation, motility, survival, mitosis and
      angiogenesis. It is overexpressed in certain type of carcinoma and fibrosarcoma
      cell lines and is associated with metastatic potential. The aim of this study was
      to investigate the relationship between Tbeta(4) expression and clinicopathologic
      features and VEGF status in gastrointestinal stromal tumors (GISTs).
      Retrospectively, 60 GISTs were re-examined and immunohistochemistry for Tbeta(4)
      and VEGF was performed. Increased expression of Tbeta(4) and VEGF was observed in
      26 (43.3%) and in 19 (31.6%) of the tumors, respectively. Tbeta(4) expression was
      positively correlated with VEGF expression (p < 0.01). Tbeta(4) and VEGF
      expression were significantly associated with tumor size (p = 0.00 and p = 0.02,
      respectively) and high mitosis (p = 0.03 and p = 0.00, respectively). Although
      Tbeta(4) expression was positively associated with pleomorphism (p = 0.01), VEGF
      expression was positively associated with necrosis (p = 0.03). Tbeta(4)
      expression was related with local recurrence and/or metastasis (p = 0.03), but
      VEGF expression was not (p = 0.12). We firstly demonstrate the presence of
      Tbeta(4) protein in GISTs. Our study reveals that increased expression of
      Tbeta(4) could be considered as an indicator of aggressive behavior of tumor.

PMID- 22882258
TI  - Concurrent emergence of multidrug resistance and heat resistance by CTX-M-15
      encoding conjugative plasmids in Klebsiella pneumoniae.
AB  - A plasmid-encoded ClpK protein was recently identified as a predictor of a heat
      resistant phenotype in the opportunistic pathogen Klebsiella pneumoniae. This
      study was undertaken to evaluate the presence of the clpK gene in extended
      spectrum beta-lactamase (ESBL)-producing K. pneumoniae and to assess the probable
      co-transfer of multi-resistance with the heat resistance phenotype. A Danish
      collection of 80 ESBL-producing K. pneumoniae bloodstream infection isolates was
      screened for clpK by colony hybridization. Nineteen isolates (24%) were positive
      for clpK; some of them representing major clones identified in Denmark. Among
      these, nine isolates belonged to a single K. pneumoniae CTX-M-15 clone with
      sequence type (ST)16 exhibiting a heat-resistant phenotype. This clone has a
      multi-hospital occurrence and has also been detected outside Denmark. Horizontal
      co-transfer of multiple antibiotic resistances, including the CTX-M-15 resistance
      determinant, and the heat resistance phenotype was observed. Thus, the clpK gene
      is harbored by different ESBL-producing K. pneumoniae isolates including a clone
      of ST16 internationally spread. The co-localization of clpK on transferable ESBL
      encoding plasmids allowing co-dissemination of multiple drug resistance with
      bacterial heat resistance is a highly interesting phenomenon that may further
      complicate the prevention of spreading of certain successful clones of multi
      resistant K. pneumoniae.

PMID- 22882259
TI  - Function of adrenomedullin in inflammatory response of liver against LPS-induced
      endotoxemia.
AB  - Adrenomedullin (AM) is a hypotension-causing peptide that was originally isolated
      from human pheochromocytoma cells, and it has been found to be expressed in
      various organs, including the liver. As the individual physiological and
      pathophysiological properties of AM peptide in the liver during endotoxemia in
      vivo has not yet been examined, we investigated this in experimental endotoxemia
      using heterozygote AM-deficient (AM(+/-)) mice. The AM concentration of AM(+/-)
      mice was significantly lesser than that of wild-type (WT) mice in
      lipopolysaccharide (LPS)-induced endotoxemia. After administering LPS, the
      survival rate for AM(+/-) mice was significantly lower than that for WT mice.
      Also, expressions of IL-1beta mRNA, and TNF-alpha mRNA, and NF-kappaB p65 in the
      liver were markedly increased and serum ALT greatly elevated in comparison with
      WT mice. However, supplementation of exogenous AM reversed the deteriorations in
      mortality and inflammatory responses. Therefore, we conclude that AM plays an
      important role in regulating systemic inflammation and may be an important
      intrinsic factor for protecting against liver damage in LPS-induced endotoxemia.

PMID- 22882260
TI  - Helicobacter pylori clarithromycin resistance detected by Etest and TaqMan real
      time polymerase chain reaction: a comparative study.
AB  - The aim of the work was to compare H. pylori clarithromycin-resistance according
      two methods. Etest was performed on H. pylori isolated from gastric biopsy
      samples. TaqMan Real-Time-PCR (RT-PCR) was performed on paraffin-embedded gastric
      biopsy samples of the same patients. Forty-seven out of 88 strains were resistant
      to clarithromycin by Etest, whereas RT-PCR detected this resistance on paraffin
      embedded specimens of 50 patients. RT-PCR performed on paraffin-embedded biopsy
      specimens of 47 patients infected with H. pylori resistant to clarithromycin as
      detected by Etest, revealed the presence of a resistant strain only in 40
      samples. RT-PCR performed on samples of 41 patients harbouring clarithromycin
      susceptible H. pylori strains showed the presence of 31 susceptible and 10
      resistant strains. RT-PCR detected 18 cases with heteroresistant status. The
      difference between the two tests in detecting clarithromycin-resistance was not
      statistically significant even if RT-PCR detected more resistant cases. The
      genotyping resistance on paraffin-embedded gastric biopsy specimens may be used
      to establish resistance to clarithromycin before the treatment when culture and
      susceptibility testing are not available. In case of failure of an empirical
      clarithromycin-based triple antimicrobial treatment, RT-PCR performed on paraffin
      embedded biopsy sample will establish the primary resistance to clarithromycin.
      In addition, this test can be useful for epidemiological investigation as well as
      for monitoring the evolution of clarithromycin resistance along the time.

PMID- 22882261
TI  - Comparing the efficacy of team based learning strategies in a problem based
      learning curriculum.
AB  - We introduced two variants of team based learning (TBL) strategies in pathology
      course to seek their efficacy in a problem based learning (PBL) curriculum. The
      TBL strategy was adopted in two different sessions. One during regular resource
      session (RS-TBL) and other during a weekly review session (RVS-TBL) of the PBL
      curriculum. The study involved 104 second year students during their 8 weeks of
      cardiovascular-respiratory units and 3 weeks of hematology units. RS-TBL was
      adopted for cardiovascular-respiratory unit and RVS-TBL for hematology unit. The
      first 8 weeks of the course were implemented as RS-TBL and the last 3 weeks as
      RVS-TBL. The results showed that the group performance was markedly improved than
      individual performance in both RS-TBL and RVS-TBL (p < 0.001). Comparison between
      the RS-TBL and RVS-TBL revealed that individual student and group performance was
      better in the RVS-BL (p < 0.001). The result of the student attitudinal survey
      indicated an 88% agreement that TBL enhanced their understanding of pathology
      concepts and critical analysis. Most of the participants (85%) found RVS-TBL to
      be more useful. Post-TBL, end of semester examination results proved beneficial
      for the students in risk. The study demonstrated that RVS-TBL may be preferably
      adopted to enhance the philosophy of TBL in a PBL curriculum.

PMID- 22882262
TI  - Evaluation of ROSCO Neo-Sensitabs for phenotypic detection and subgrouping of
      ESBL-, AmpC- and carbapenemase-producing Enterobacteriaceae.
AB  - The increasing prevalence of ESBL-, AmpC- and carbapenemase-producing
      Enterobacteriaceae necessitates reliable phenotypic tests for detection and
      categorization. The main objective of this study was to evaluate ROSCO Neo
      Sensitabs with different beta-lactam-beta-lactam inhibitor combinations for
      phenotypic detection and categorization of beta-lactamases in Enterobacteriaceae.
      Using standard CLSI/EUCAST methodology, differences in zones of inhibitions
      between a beta-lactam alone compared with the combination with a beta-lactamase
      inhibitor as well as subjective synergy observations were determined for 172 well
      characterized Enterobacteriaceae strains with defined resistance mechanisms. The
      results showed that for all ESBL-positive strains (n = 66), combinations of
      clavulanic acid synergy with cefotaxime, ceftazidime or cefepime, were observed.
      All acquired AmpC beta-lactamases (n = 17) were detected using cloxacillin
      combined with cefotaxime and/or ceftazidime (both combinations were required).
      Carbapenemase producers (n = 59) with the exception of one KPC-producer were
      correctly grouped using the combination of meropenem +/- aminophenylboronic acid
      (APBA) or dipicolinic acid (DPA). Ethylene diamine tetraacetic acid (EDTA) also
      inhibited all metallo-beta-lactamases, but as with DPA, one false positive result
      was observed. Based upon these data, we propose a tablet layout for 14 cm agar
      plates, which could be used as a whole or in a targeted approach for detection
      and categorizing of relevant acquired beta-lactamases in Enterobacteriaceae.

PMID- 22882263
TI  - Effect of alkaline pH on staphylococcal biofilm formation.
AB  - Biofilms are a serious problem, cause of severe inconvenience in the biomedical,
      food and industrial environment. Staphylococcus aureus and S. epidermidis are
      important pathogenic bacteria able to form thick and resistant biofilms on
      various surfaces. Therefore, strategies aimed at preventing or at least
      interfering with the initial adhesion and subsequent biofilm formation are a
      considerable achievement. The aim of this study was to evaluate the effect of
      alkaline pH on bacterial adhesion and further biofilm formation of S. aureus and
      S. epidermidis strains by biofilm biomass, cell-surface hydrophobicity, scanning
      electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) analysis.
      The results demonstrated that the amount of biofilm biomass formed and the
      surface hydrophobicity were significantly less than what were observed at higher
      levels of pH. SEM and CLSM images revealed a poorly structured and very thin
      biofilm (2.5-3 times thinner than that of the controls). The inhibiting effect of
      the alkaline pH on the bacterial attachment impaired the normal development of
      biofilm that arrested at the microcolony stage. Alkaline formulations could be
      promising towards the control of bacterial colonization and therefore the
      reduction of the biofilm-related hazard. In the clinical setting, alkaline
      solutions or cleaners could be promising to prevent the bacterial colonization,
      by treating surfaces such as catheters or indwelling medical devices, reducing
      the risk of biofilm related infections.

PMID- 22882264
TI  - Characterization of Rhodopseudomonas palustris strain 2C as a potential
      probiotic.
AB  - Photosynthetic bacteria (PSB) are prokaryotes that first appeared on the earth 2
      billion years ago. Being rich in nutrients and having unique biological
      transformational function, PSB have been used as medicinal ingredients and
      healthcare products. However, there is insufficient information about the
      probiotic properties of PSB. The aim of this study was to characterize the
      potential probiotic properties of Rhodopseudomonas palustris strain 2C. The
      tolerance of strain 2C to low pH, high bile salt and simulated gastrointestinal
      conditions was determined. The susceptibility of strain 2C to 11 antibiotics was
      screened. The in vitro antioxidative activity and acute toxicity of strain 2C
      were performed. The survival duration of strain 2C after it had been repeatedly
      ingested by Wistar rats was determined. Strain 2C was tolerant to low pH, high
      bile salt concentration, and simulated gastrointestinal conditions. Strain 2C was
      only resistant to two of the 11 tested antibiotics (penicillin and ampicillin),
      and it showed antioxidative activity in vitro. When ingested by rats, strain 2C
      did not cause any bacteria translocation or tissue damage. The survival duration
      of strain 2C depending on doses ingested by the rats, 3 days after the
      termination of intake, it could no longer be enriched from the feces. Taken
      together, these findings indicate that strain 2C may be a potential probiotic
      strain.

PMID- 22882265
TI  - Novel meningococcal 4CMenB vaccine antigens - prevalence and polymorphisms of the
      encoding genes in Neisseria gonorrhoeae.
AB  - The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B),
      the protein-based 4 component meningococcus serogroup B (4CMenB), includes the
      New Zealand outer membrane vesicle and three main genome-derived neisserial
      antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030)
      and NadA. In this study, the prevalence and polymorphisms of the nucleotide and
      amino acid sequences of the 4CMenB antigens in a temporally and geographically
      diverse collection of N. gonorrhoeae isolates (n = 111) were investigated. All
      the examined GNA genes, except the nadA gene, were present in all gonococcal
      isolates. However, 25 isolates contained premature stop codons in the fHbp gene
      and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB
      antigen sequences in reference strain MC58, the gonococcal strains displayed 67.0
      95.4% and 60.9-94.9% identity in nucleotide sequence and amino acid sequence,
      respectively, in the equivalent GNA antigens. The absence of NadA, lack of
      universal expression of fHbp and NHBA and the uncertainty regarding the surface
      exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely
      limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However,
      possible cross-immunity of 4CMenB with gonococci and expression and function of
      the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a
      gonococcal vaccine, need to be further examined.

PMID- 22882266
TI  - Effects of lipopolysaccharide infusion on arterial levels and transcerebral
      exchange kinetics of glutamate and glycine in healthy humans.
AB  - An imbalance between glutamate and glycine signalling may contribute to sepsis
      associated encephalopathy by causing neuronal excitotoxicity. In this study, we
      therefore investigated the transcerebral exchange kinetics of glutamate and
      glycine in a human-experimental model of systemic inflammation. Cerebral blood
      flow (CBF) and arterial to jugular venous concentration differences of glutamate
      and glycine were determined before and after a 4-h intravenous infusion of
      Escherichia coli lipopolysaccharide (LPS, total dose of 0.3 ng/kg) in 12 healthy
      volunteers. The global cerebral net exchange was calculated by multiplying CBF
      with the arterial to jugular venous differences. LPS induced a systemic
      inflammatory response with fever, neutrocytosis, and elevated arterial levels of
      tumour necrosis factor-alpha. This was associated with a decrease in the arterial
      levels of both glutamate and glycine; however, their transcerebral exchange
      kinetics were unaffected. Inflammation-induced alterations of the circulating
      levels of glutamate and glycine, do not affect the global transcerebral exchange
      kinetics of these amino acids in healthy humans.

PMID- 22882267
TI  - Are differentially expressed microRNAs useful in the diagnostics of malignant
      pleural mesothelioma?

PMID- 22882268
TI  - Somatic mutation of PINX1 gene is rare in common solid cancers.

PMID- 22882269
TI  - Pathological differentiation of chronic hypersensitivity pneumonitis from
      idiopathic pulmonary fibrosis/usual interstitial pneumonia.
AB  - AIMS: To evaluate the histological characteristics differentiating chronic
      hypersensitivity pneumonitis (chronic HP) with a usual interstitial pneumonia
      (UIP)-like pattern from idiopathic pulmonary fibrosis (IPF)/UIP. METHODS AND
      RESULTS: Surgical lung biopsy specimens from 22 patients with chronic HP
      diagnosed as having a UIP-like pattern upon histological examination and 13
      patients with IPF/UIP were examined and the incidences of bronchiolitis,
      perilobular fibrosis, centrilobular fibrosis, bridging fibrosis, organizing
      pneumonia, fibroblastic foci, honeycombing, granulomas, giant cells, lymphocytic
      alveolitis and lymphoid follicles were compared. Bronchiolitis, centrilobular
      fibrosis, bridging fibrosis, organizing pneumonia, granulomas, giant cells and
      lymphocytic alveolitis were significantly more frequent among patients with
      chronic HP than among patients with IPF (all P<0.01). CONCLUSIONS: Centrilobular
      fibrosis, bridging fibrosis and organizing pneumonia, in addition to
      bronchiolitis, granulomas and giant cells, are characteristic features of chronic
      HP with a UIP-like pattern. These features are therefore important in
      differentiating chronic HP from IPF/UIP, as management strategies differ for the
      two disorders.

PMID- 22882271
TI  - Creatureliness priming reduces aggression and support for war.
AB  - Terror management theory (TMT) posits that humans distance themselves from, or
      elevate themselves above, other animals as a way of denying their mortality. The
      present studies assessed whether the salience of aggressive tendencies that
      humans share with other animals make thoughts of death salient and whether
      depicting human aggression as animalistic can mitigate aggressive behaviour and
      support for aggression. In Study 1, participants primed with human-animal
      similarities (i.e., human creatureliness) exhibited elevated death-thought
      accessibility (DTA) after hitting a punching bag. In Studies 2a and 2b,
      creatureliness priming caused participants to hit a punching bag with less
      frequency, perceived force, and comfort. In Study 3, participants primed to view
      violence as animalistic exhibited increased DTA and reported less support for war
      against Iran. These studies suggest that portraying violence as creaturely may
      reduce the intensity of aggressive actions and support for violent solutions to
      international conflicts. 

PMID- 22882270
TI  - A subset of human uterine endometrial macrophages is alternatively activated.
AB  - PROBLEM: Human uterine macrophages must maintain an environment hospitable to
      implantation and pregnancy and simultaneously provide protection against
      pathogens. Although macrophages comprise a significant portion of leukocytes
      within the uterine endometrium, the activation profile and functional response of
      these cells to endotoxin are unknown. METHOD OF STUDY: Flow cytometric analysis
      of surface receptors and intracellular markers expressed by macrophages isolated
      from human endometria was performed. Uterine macrophages were stimulated with
      LPS. Cytokines, chemokines, and growth factors expressed by these cells were
      analyzed using Bio-Plex analysis. RESULTS: CD163(high) human endometrial
      macrophages constitutively secrete both pro- and anti-inflammatory cytokines as
      well as pro-angiogenic factors and secretion of these factors is LPS-inducible.
      CONCLUSION: A major population of human uterine macrophages is alternatively
      activated. These cells secrete factors in response to LPS that are involved in
      the activation of immune responses and tissue homeostasis.

PMID- 22882272
TI  - Genetic variants associated with myocardial infarction in the PSMA6 gene and
      Chr9p21 are also associated with ischaemic stroke.
AB  - BACKGROUND: Ischaemic stroke shares common traditional risk factors with coronary
      artery disease (CAD) and myocardial infarction (MI). This study evaluated whether
      genetic risk factors for CAD and MI also affect susceptibility to ischaemic
      stroke in Caucasians and African Americans. METHODS: Included in the study were a
      Caucasian series (713 ischaemic stroke patients, 708 controls) and a small
      African American series (166 ischaemic stroke patients, 117 controls). Twenty
      single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD
      or MI were genotyped and assessed for association with ischaemic stroke and
      ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic
      regression models. RESULTS: In Caucasians, four SNPs on chromosome 9p21 were
      significantly associated with risk of cardioembolic stroke, the strongest of
      which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were
      observed for small vessel stroke, with no associations observed regarding large
      vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic
      stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P
      = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome
      14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P
      = 0.036) and African Americans (OR 0.31, P = 0.020). CONCLUSIONS: Our results
      provide evidence that chromosome 9p21 variants are associated with cardioembolic
      ischaemic stroke in Caucasians and with overall ischaemic stroke in African
      Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to
      ischaemic stroke in both populations. These findings require validation,
      particularly the preliminary findings regarding African Americans given the small
      size of that series.

PMID- 22882274
TI  - Long-term outcome in occipital nerve stimulation patients with medically
      intractable primary headache disorders.
AB  - INTRODUCTION: ?? Occipital nerve stimulation (ONS) may provide relief for
      refractory headache disorders. However, scant data exist regarding long-??term
      ONS outcomes. METHODS: ?? The methods used were retrospective review of the
      medical records of all (nonindustry study) patients who were trialed and
      implanted with occipital nerve stimulator systems at our institution, followed by
      a phone interview. Up to three attempts were made to contact each patient, and
      those who were contacted were given the opportunity to participate in a brief
      phone interview regarding their ONS experience. Data for analysis were gleaned
      from both the phone interview and the patient's medical records. RESULTS: ??
      Twenty-nine patients underwent a trial of ONS during the 8.5-?year study period.
      Three patients did not go on to permanent implant, 12 could not be contacted, and
      14 participated in the phone interview. Based upon the phone interview (if the
      patient was contacted) or chart review, ONS was deemed successful in five of the
      12 migraine, four of the five cluster headache, and five of the eight
      miscellaneous headache patients, and therapy was documented as long as 102
      months. In one of the 26 patients, success of ONS could not be determined. Among
      patients deemed to have successful outcomes, headache frequency decreased by 18%,
      severity by 27%, and migraine disability score by 50%. Fifty-??eight percent of
      patients required at least one lead revision. DISCUSSION: ?? These results,
      although limited by their retrospective nature, suggest that ONS can be effective
      long term despite technical challenges. The number of patients within each
      headache subtype was insufficient to draw conclusions regarding the differential
      effect of ONS. CONCLUSIONS: ?? Randomized controlled long-??term studies in
      specific, intractable, primary headache disorders are indicated.

PMID- 22882275
TI  - Metformin and the thyroid: some questions still remain.

PMID- 22882276
TI  - The inhibitory effects of aureobasidin A on Candida planktonic and biofilm cells.
AB  - Aureobasidin A (AbA) is a cyclic depsipeptide antifungal compound that inhibits a
      wide range of pathogenic fungi. In this study, the in vitro susceptibility of 92
      clinical isolates of various Candida species against AbA was assessed by
      determining the planktonic and biofilm MICs of the isolates. The MIC(50) and
      MIC(90) of the planktonic Candida yeast were 1 and 1 MUg ml(-1), respectively,
      whereas the biofilm MIC(50) and MIC(90) of the isolates were 8 and >=64 MUg ml(
      1) respectively. This study demonstrates AbA inhibition on filamentation and
      biofilm development of C. albicans. The production of short hyphae and a lack of
      filamentation might have impaired biofilm development of AbA-treated cells. The
      AbA resistance of mature Candidia biofilms (24 h adherent population) was
      demonstrated in this study.

PMID- 22882273
TI  - Cryptic species, native populations and biological invasions by a eucalypt forest
      pathogen.
AB  - Human-associated introduction of pathogens and consequent invasions is very
      evident in areas where no related organisms existed before. In areas where
      related but distinct populations or closely related cryptic species already
      exist, the invasion process is much harder to unravel. In this study, the
      population structure of the Eucalyptus leaf pathogen Teratosphaeria nubilosa was
      studied within its native range in Australia, including both commercial
      plantations and native forests. A collection of 521 isolates from across its
      distribution was characterized using eight microsatellite loci, resulting in 112
      multilocus haplotypes (MLHs). Multivariate and Bayesian analyses of the
      population conducted in structure revealed three genetically isolated groups (A,
      B and C), with no evidence for recombination or hybridization among groups, even
      when they co-occur in the same plantation. DNA sequence data of the ITS (n = 32),
      beta-tubulin (n = 32) and 27 anonymous loci (n = 16) were consistent with
      microsatellite data in suggesting that T. nubilosa should be considered as a
      species complex. Patterns of genetic diversity provided evidence of biological
      invasions by the pathogen within Australia in the states of Western Australia and
      New South Wales and helped unravel the pattern of invasion beyond Australia into
      New Zealand, Brazil and Uruguay. No significant genetic differences in pathogen
      populations collected in native forests and commercial plantations were observed.
      This emphasizes the importance of sanitation in the acquisition of nursery stock
      for the establishment of commercial plantations.

PMID- 22882277
TI  - Effects of temperatures near the freezing point on N2O emissions, denitrification
      and on the abundance and structure of nitrifying and denitrifying soil
      communities.
AB  - Climate warming in temperate regions may lead to decreased soil temperatures over
      winter as a result of reduced snow cover. We examined the effects of temperatures
      near the freezing point on N(2)O emissions, denitrification, and on the abundance
      and structure of soil nitrifiers and denitrifiers. Soil microcosms supplemented
      with NO3 - and/or NO3 - plus red clover residues were incubated for 120 days at 
      4  degrees C, -1  degrees C, +2  degrees C or +5  degrees C. Among microcosms
      amended with residues, N(2)O emission and/or denitrification increased with
      increasing temperature on Days 2 and 14. Interestingly, N(2)O emission and/or
      denitrification after Day 14 were the greatest at -1  degrees C. Substantial N(2)
      O emissions were only observed on Day 2 at +2  degrees C and +5  degrees C, while
      at -1  degrees C, N(2)O emissions were consistently detected over the duration of
      the experiment. Abundances of ammonia oxidizing bacteria (AOB) and archaea (AOA),
      Nitrospira-like bacteria and nirK denitrifiers were the lowest in soils at -4 
      degrees C, while abundances of Nitrobacter-like bacteria and nirS denitrifiers
      did not vary among temperatures. Community structures of nirK and nirS
      denitrifiers and Nitrobacter-like bacteria shifted between below-zero and above
      zero temperatures. Structure of AOA and AOB communities also changed but not
      systematically among frozen and unfrozen temperatures. Results indicated shifts
      in some nitrifier and denitrifier communities with freezing and a surprising
      stimulation of N(2)O emissions at -1  degrees C when NO3 - and C are present.

PMID- 22882278
TI  - The consequences of lifetime and evolutionary exposure to toxic prey: changes in
      avoidance behaviour through ontogeny.
AB  - Responses to novel threats (e.g. invasive species) can involve genetic changes or
      plastic shifts in phenotype. There is controversy over the relative importance of
      these processes for species survival of such perturbations, but we are realizing
      they are not mutually exclusive. Native eastern fence lizards (Sceloporus
      undulatus) have adapted to top-down predation pressure imposed by the invasive
      red imported fire ant (Solenopsis invicta) via changes in adult (but not
      juvenile) lizard antipredator behaviour. Here, we examine the largely ignored,
      but potentially equally important, bottom-up effect of fire ants as toxic prey
      for lizards. We test how fire ant consumption (or avoidance) is affected by
      lifetime (via plasticity) and evolutionary (via natural selection) exposure to
      fire ants by comparing field-caught and laboratory-reared lizards, respectively,
      from fire ant-invaded and uninvaded populations. More naive juveniles from
      invaded populations ate fire ants than did adults, reflecting a natural
      ontogenetic dietary shift away from ants. Laboratory-reared lizards from the
      invaded site were less likely to eat fire ants than were those from the uninvaded
      site, suggesting a potential evolutionary shift in feeding behaviour. Lifetime
      and evolutionary exposure interacted across ontogeny, however, and field-caught
      lizards from the invaded site exhibited opposite ontogenetic trends; adults were
      more likely to eat fire ants than were juveniles. Our results suggest that
      plastic and evolutionary processes may both play important roles in permitting
      species survival of novel threats. We further reveal how complex interactions can
      shape adaptive responses to multimodal impacts imposed by invaders: in our
      system, fire ants impose stronger bottom-up selection than top-down selection,
      with each selection regime changing differently across lizard ontogeny.

PMID- 22882279
TI  - Stoichiometric patterns in foliar nutrient resorption across multiple scales.
AB  - * Nutrient resorption is a fundamental process through which plants withdraw
      nutrients from leaves before abscission. Nutrient resorption patterns have the
      potential to reflect gradients in plant nutrient limitation and to affect a suite
      of terrestrial ecosystem functions. * Here, we used a stoichiometric approach to
      assess patterns in foliar resorption at a variety of scales, specifically
      exploring how N : P resorption ratios relate to presumed variation in N and/or P
      limitation and possible relationships between N : P resorption ratios and soil
      nutrient availability. * N : P resorption ratios varied significantly at the
      global scale, increasing with latitude and decreasing with mean annual
      temperature and precipitation. In general, tropical sites (absolute latitudes <
      23 degrees 26') had N : P resorption ratios of < 1, and plants growing on highly
      weathered tropical soils maintained the lowest N : P resorption ratios.
      Resorption ratios also varied with forest age along an Amazonian forest
      regeneration chronosequence and among species in a diverse Costa Rican rain
      forest. * These results suggest that variations in N : P resorption stoichiometry
      offer insight into nutrient cycling and limitation at a variety of spatial
      scales, complementing other metrics of plant nutrient biogeochemistry. The extent
      to which the stoichiometric flexibility of resorption will help regulate
      terrestrial responses to global change merits further investigation.

PMID- 22882280
TI  - Myrmecia wart inclusions as an incidental histopathologic finding.
AB  - BACKGROUND: Latent infection by human papillomavirus (HPV) has been described for
      genital (mucosal) and epidermodysplasia verruciformis subtypes. Only rarely has
      cutaneotropic, non-oncogenic HPV been found by polymerase chain reaction studies
      in normal skin. METHODS: We noted myrmecia wart inclusions as an incidental
      histopathologic finding in four specimens from diverse sites (eyebrow, scalp,
      forehead, leg). The final diagnoses for these four cases were intradermal nevus,
      scarring alopecia, benign keratosis and stasis dermatitis. Anti-HPV antibody
      staining was performed in all cases. This antibody detects HPV-1,6,11,16,18 and
      31 in formalin-fixed paraffin-embedded tissue. RESULTS: The foci of myrmecia wart
      inclusions were characterized by smooth to angular cytoplasmic inclusions in the
      granular layer, spanning one to three rete. The inclusions stained with an anti
      HPV antibody in three specimens. CONCLUSIONS: This finding of incidental myrmecia
      wart inclusions in skin biopsies supports latent infection by cutaneotropic, non
      carcinogenic HPV.

PMID- 22882282
TI  - Vacuum-assisted deliveries and the risk of obstetric anal sphincter injuries-a
      retrospective register-based study in Finland.
AB  - OBJECTIVES: To identify and quantify the risks of obstetric anal sphincter injury
      (OASIS) separately in nulliparae, including women admitted for a first vaginal
      delivery after a previous caesarean section for their first birth, and multiparae
      delivered by vacuum extraction in Finland where the type of episiotomy is
      exclusively lateral. DESIGN: A retrospective population-based register study.
      METHODS: Nulliparous and multiparous women with OASIS were compared separately
      with women without OASIS using stepwise logistic regression analysis. MAIN
      OUTCOME MEASURES: Risk of OASIS. RESULTS: Among a sample of 16,802 women whose
      infants were delivered by vacuum extraction between 2004 and 2007, the incidence
      of OASIS was significantly higher among nulliparous women (475 of 13,981, 3.4%)
      than multiparous women (40 of 2821, 1.4%), with adjusted odds ratio 2.44 (95% CI
      1.77-3.39). Lateral episiotomy was associated with 46% decreased incidence of
      OASIS (adjusted odds ratio 0.54, 95% CI 0.42-0.70) in nulliparae delivered by
      vacuum extraction. There was no statistically significant association for
      multiparous women. An increase of 1000 g in birthweight increased the OASIS
      incidence 2.10-fold for nulliparae and 2.83-fold for multiparae. CONCLUSIONS:
      Nulliparous women with infants delivered by vacuum extraction had an increased
      risk of OASIS compared with multiparous women. Lateral episiotomy was associated
      with a decreased incidence of OASIS, especially in women with large babies and
      long second stage. These results support liberal use of lateral episiotomy at
      vacuum extraction for nulliparous women at high risk of OASIS, but the role of
      episiotomy should be re-investigated in interventional randomised trials.

PMID- 22882281
TI  - Exenatide at therapeutic and supratherapeutic concentrations does not prolong the
      QTc interval in healthy subjects.
AB  - AIMS: Exenatide has been demonstrated to improve glycaemic control in patients
      with type 2 diabetes, with no effect on heart rate corrected QT (QTc ) at
      therapeutic concentrations. This randomized, placebo- and positive-controlled,
      crossover, thorough QT study evaluated the effects of therapeutic and
      supratherapeutic exenatide concentrations on QTc . METHODS: Intravenous infusion
      was employed to achieve steady-state supratherapeutic concentrations in healthy
      subjects within a reasonable duration (i.e. days). Subjects received exenatide,
      placebo and moxifloxacin, with ECGs recorded pre-therapy and during treatment.
      Intravenous exenatide was expected to increase heart rate to a greater extent
      than subcutaneous twice daily or once weekly formulations. To assure proper heart
      rate correction, a wide range of baseline heart rates was assessed and
      prospectively defined methodology was applied to determine the optimal QT
      correction. RESULTS: Targeted steady-state plasma exenatide concentrations were
      exceeded (geometric mean +/- SEM 253 +/- 8.5 pg ml(-1) , 399 +/- 11.9 pg ml(-1)
      and 627 +/- 21.2 pg ml(-1) ). QTc P, a population-based method, was identified as
      the most appropriate heart rate correction and was prespecified for primary
      analysis. The upper bound of the two-sided 90% confidence interval for placebo
      corrected, baseline-adjusted QTc P (DeltaDeltaQTc P) was <10 ms at all time
      points and exenatide concentrations. The mean of three measures assessed at the
      highest steady-state plasma exenatide concentration of ~500 pg ml(-1)
      (DeltaDeltaQTc P(avg) ) was -1.13 [-2.11, -0.15). No correlation was observed
      between DeltaDeltaQTc P and exenatide concentration. Assay sensitivity was
      confirmed with moxifloxacin. CONCLUSIONS: These results demonstrated that
      exenatide, at supratherapeutic concentrations, does not prolong QTc and provide
      an example of methodology for QT assessment of drugs with an inherent heart rate
      effect.

PMID- 22882283
TI  - Effect of physician dress style on patient confidence.
AB  - BACKGROUND: We lack data on how physicians can instill confidence in patients.
      OBJECTIVES: We aimed to determine whether dress style (professional white coat or
      formal, semiformal or casual attire) affects confidence in the physician by
      patients (children, teenagers, adults) with dermatology complaints consulting in
      the hospital or private practice. METHODS: Design. Descriptive prospective cross
      sectional study carried out from July 1, 2008 to July 1, 2009. Setting.
      Outpatients in the department of dermatology of a French tertiary care hospital,
      and two dermatological private consulting rooms. Participants and design.
      Consulting patients were >= 7 years and classified as children 7-11 years old,
      accompanying parents, teenagers (12-17 years), and adults >= 18 years consulting
      alone. Subjects viewed two iconographic boards containing 4 photographs in a
      random order of a male physician on 1 board and a female physician on the other
      board in 4 different dress styles: professional (white coat and stethoscope),
      formal (shirt and tie for men), semiformal, and casual (T-shirt, jeans). Subjects
      then completed a questionnaire asking them to rate, on a scale of 0-10, their
      confidence in the physicians portrayed and answered whether they considered
      physician dress important. Main outcomes and measures. The main outcome was
      subjects' ranking of photos of physicians by dress style, according to the
      confidence they felt. For children 7-11 years old, we considered the frequency of
      the chosen dress style. The secondary outcome was whether physician dress was
      important to patients. RESULTS: We included 329 patients. Children at the
      hospital most frequently chose the photo of the physician, both male (62%) and
      female (64%), with the white coat. Teenagers' choices were professional dress,
      then semiformal, formal, and casual attire. Accompanying adults and adults
      consulting alone had the same ranking. CONCLUSIONS: In France, patients of all
      ages who consult for dermatology complaints in hospital and in private practice
      have the most confidence in a physician who wears a professional white coat.

PMID- 22882284
TI  - Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and
      novel treatments.
AB  - Hidradenitis suppurativa (HS) is an inflammatory, debilitating follicular skin
      disease with recurring flare-ups. The painful, deep-seated, inflamed lesions in
      the inverse areas of the body cause severe discomfort, and hence, serious psycho
      social and economic costs. HS is common, but often misdiagnosed and
      mechanistically poorly understood. Furthermore, HS is notoriously difficult to
      treat resulting in a high unmet medical need. To provoke debate, rational
      experimentation and initiate strategic studies, we here present a concise
      viewpoint on seven topics: the diagnosis of HS, the role of mechanical friction,
      the critical importance of accurate clinical subgrouping, smoking and obesity,
      the role of bacteria, and our comprehensive view on HS pathogenesis with a
      central role for keratin clearance, and novel treatment approaches.

PMID- 22882285
TI  - The efficacy of the use of intravenous human immunoglobulin in Brazilian newborns
      with rhesus hemolytic disease: a randomized double-blind trial.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of intravenous
      human immunoglobulin (IVIG) in the presence of high-intensity phototherapy in
      decreasing the need for exchange transfusion in newborns with rhesus hemolytic
      disease. STUDY DESIGN AND METHODS: We performed a randomized, double-blind,
      placebo-controlled trial. The trial included D+ newborns born at 32 weeks of
      gestational age or later with a positive direct antiglobulin test and whose
      mothers were Rh-alloimmunized and did or did not receive intrauterine
      transfusion. The newborns were randomly assigned to receive either IVIG at a dose
      of 500 mg/kg or placebo (saline solution, 10 mL/kg) during the first 6 hours of
      life. The primary outcome was the need for exchange transfusion. The criteria for
      exchange transfusion were total serum bilirubin (TSB) level at or above 340
      umol/L (20 mg/dL) or increasing by 8.5 umol/L/hr (0.5 mg/dL/hr) despite intensive
      phototherapy. RESULTS: The trial included 92 newborns. There was no difference in
      the rate of exchange transfusion between groups: 6 of 46 (13%) in the IVIG group
      versus 7 of 46 (15.2%) in the placebo group (p = 0.765). There were no
      significant differences between groups with respect to their need for exchange
      transfusion, phototherapy time, peak bilirubin, or length of hospital stay. There
      were no adverse events related to the drug or the form of administration.
      CONCLUSION: Nonspecific human immunoglobulin was not effective in preventing the
      need for exchange transfusion in neonates with rhesus hemolytic disease.

PMID- 22882286
TI  - Gastrointestinal manifestations of cow's milk protein allergy and
      gastrointestinal motility.
AB  - Cow's milk protein allergy (CMPA) may cause gastrointestinal motility disorders.
      Symptoms of both conditions overlap and diagnostic tests do not reliably
      differentiate between both. A decrease of symptoms with an extensive hydrolysate
      and relapse during challenge is not a proof of allergy, because hydrolysates
      enhance gastric emptying, a pathophysiologic mechanism of gastro-oesophageal
      reflux (GER). Thickened formula reduces regurgitation, and failure to do so
      suggests CMPA. A thickened extensive hydrolysate may induce more rapid
      improvement, but does not always differentiate between CMPA and GER. Different
      hypotheses are discussed: is the overlap between CMPA and functional disorders
      coincidence, or do both entities present with identical symptoms, or does the
      fact that symptoms are identical indicates that there is only one entity
      involved? Studies on the prevention of CMPA focused on 'at-risk families', and
      resulted in a decrease of CMPA and atopic dermatitis, but did not provide data on
      the incidence of GER. CONCLUSION:   As long as there are no objective diagnostic
      tools to separate GER from CMPA, the physician has two options: first treat the
      most likely diagnosis, and switch if after 2-4 weeks there is no improvement, or
      treat both conditions with one intervention, what will not result in a diagnosis.

PMID- 22882288
TI  - Effects of aggressive parenteral nutrition on growth and clinical outcome in
      preterm infants.
AB  - BACKGROUND: The goal of nutrition in the preterm infant is to achieve postnatal
      growth approximating normal fetal growth. During the early postnatal period,
      protein intake must be sufficient to achieve normal postnatal growth in extremely
      low-birthweight infants. The aim of this study was to test the hypothesis that
      giving higher amounts of amino acids and lipids to infants born at <34
      gestational weeks (GW) may improve growth at the 40th week of gestation and have
      a positive preventive effect on development of retinopathy of prematurity (ROP).
      METHODS: Fifty-three neonates born at <34 GW and hospitalized in the neonatal
      intensive care unit (NICU) were included in this prospective study. They were
      randomly divided into two groups. Group 1 received aggressive parenteral
      nutrition (PN) (amino acids 3 g/kg per day and lipids 2 g/kg per day on first day
      of life). Group 2 received conventional PN (amino acids 1.5 g/kg per day and
      lipids 1 g/kg per day on first day of life). The anthropometric measurements,
      clinical outcomes and serum levels of insulin-like growth factor-I (IGF-I), IGF
      binding protein (IGFBP) and thyroid hormones were compared between groups.
      RESULTS: At 40 weeks of gestation, height, head circumference and serum IGF-I and
      IGFBP3 were statistically higher in the group receiving aggressive PN. Thyroid
      hormones were not affected by aggressive PN. The lower levels of IGF-I and IGFBP3
      in the group receiving conventional PN were negatively correlated with
      development of ROP. CONCLUSION: Aggressive PN seems to positively affect
      neonates' anthropometric measurements at the 40th gestational week and the
      development of ROP. These effects may be related to high levels of IGF-I and
      IGFBP3.

PMID- 22882287
TI  - Frontotemporal anatomical connectivity and working-relational memory performance
      predict everyday functioning in schizophrenia.
AB  - Hippocampal (relational memory) and prefrontal cortex (PFC; working memory)
      impairments have been found in patients with schizophrenia (SP), possibly due to
      a dysfunctional connection between structures. Neuroanatomical studies that
      describe reduced fractional anisotropy (FA) in the uncinate fasciculus support
      this idea. The dysconnection hypothesis in SP was investigated by examining
      frontotemporal anatomical connectivity (uncinate fasciculus FA) and PFC
      hippocampal memory and their relationship with each other and everyday
      functioning. PFC-hippocampal memory was examined with two working-relational
      memory tasks: transverse patterning and a virtual Morris water task. SP exhibited
      a performance deficit on both tasks and had lower FA in bilateral uncinate
      fasciculus than healthy volunteers. Lower frontotemporal anatomical connectivity
      was related to lower working-relational memory performance, and both predicted
      worse everyday functioning.

PMID- 22882289
TI  - Virtual reality microscope versus conventional microscope regarding time to
      diagnosis: an experimental study.
AB  - AIMS:   To create and evaluate a virtual reality (VR) microscope that is as
      efficient as the conventional microscope, seeking to support the introduction of
      digital slides into routine practice. METHODS AND RESULTS:   A VR microscope was
      designed and implemented by combining ultra-high-resolution displays with VR
      technology, techniques for fast interaction, and high usability. It was evaluated
      using a mixed factorial experimental design with technology and task as within
      participant variables and grade of histopathologist as a between-participant
      variable. Time to diagnosis was similar for the conventional and VR microscopes.
      However, there was a significant difference in the mean magnification used
      between the two technologies, with participants working at a higher level of
      magnification on the VR microscope. CONCLUSIONS:   The results suggest that, with
      the right technology, efficient use of digital pathology for routine practice is
      a realistic possibility. Further work is required to explore what magnification
      is required on the VR microscope for histopathologists to identify diagnostic
      features, and the effect on this of the digital slide production process.

PMID- 22882290
TI  - Studies in rodents with the dipeptidyl peptidase-4 inhibitor vildagliptin to
      evaluate possible drug-induced pancreatic histological changes that are
      predictive of pancreatitis and cancer development in man.
AB  - AIM: The present report summarizes rodent studies with vildagliptin, relevant to
      predicting pancreatitis or pancreatic cancer in man. METHODS: As part of the
      regulatory development program for vildagliptin, a rodent toxicity program
      included two 104-week rodent (mouse and rat) carcinogenicity studies that were
      conducted according to guidelines assigned in Food and Drug Administration's
      Draft Guidance for Industry. RESULTS: Vildagliptin exposure in animals was
      evaluated for its effects on endocrine and exocrine pancreas. Two-year
      carcinogenicity studies were conducted in rats at oral doses up to 900 mg/kg
      (approximately 200 times the human exposure at the maximum recommended dose) and
      in mice at oral doses up to 1000 mg/kg (up to 240 times the human exposure at the
      maximum recommended dose). The results from these studies show the expected
      preservation and growth of the endocrine beta-cells with no significant findings
      in the exocrine acinar pancreas. There was no evidence of inflammatory
      infiltrates characteristic of pancreatitis, no palpable mass detection based on
      gross examination or any microscopic findings indicative of pancreatic islet cell
      (endocrine), acinar cell (exocrine) or ductal (exocrine) neoplasia in rat or
      mouse. CONCLUSIONS: Evaluation of vildagliptin in 2-year preclinical
      carcinogenicity studies in both rats and mice indicates that while vildagliptin
      results in pharmacological benefits to the endocrine pancreas, this was not
      associated with any evidence of pancreatitis, pancreatic islet cell, acinar cell
      or ductal neoplasia. These data predict no increased risk of pancreatic cancer in
      man.

PMID- 22882291
TI  - Clinical manifestations and treatment for keratocystic odontogenic tumors
      associated with nevoid basal cell carcinoma syndrome: a study in 25 Japanese
      patients.
AB  - BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant
      disorder and is characterized by tumorigenesis and physical deformity.
      Keratocystic odontogenic tumors (KCOTs) of the jaws are a common manifestation of
      this syndrome. This study involved a pooled analysis of Japanese individuals with
      NBCCS and was performed with the aim of analyzing the clinical features of NBCCS
      and the patterns of occurrence and recurrence of KCOTs in Japanese individuals.
      METHODS: This study included 25 patients. The relative frequencies of the major
      symptoms in these patients were compared with those reported in the literature.
      We also investigated 11 patients with KCOTs (40 lesions) initially treated at
      Tokyo Medical and Dental University. RESULTS: KCOTs (100%) and palmar and/or
      plantar pits (n = 19; 76.0%) were the most frequently observed manifestations.
      Eleven patients (44.0%) had a radiologically confirmed rib anomaly. Nineteen
      patients (76.0%) had a family history of the syndrome within first-degree
      relatives. Japanese patients had a relatively low frequency of basal cell
      carcinoma (n = 7; 28.0%) and falx calcification (n = 7; 28.0%) compared with that
      reported in other populations. Twelve of the total 40 KCOTs (30.0%) that were
      followed up for 6 months or more recurred. All recurrent cases had undergone
      conservative treatment, whereas no recurrences occurred in cases that had
      undergone radical treatment. CONCLUSIONS: Recurrence of KCOTs associated with
      NBCCS is frequently encountered, and further investigations are required to
      confirm the optimal treatment that will ensure a complete cure improving the
      patient's quality of life.

PMID- 22882292
TI  - Long-term results for maxillary rehabilitation with dental implants after tumor
      resection.
AB  - BACKGROUND: Defects of the maxilla due to tumor extirpation can create
      accordingly high levels of psychological and physical trauma for patients and
      their families. However, the reconstruction of maxillary defects remains very
      challenging. Today, using autogenous bone grafts and dental implants is an
      effective method to restore maxillary defects. PURPOSE: The purpose of this study
      was to evaluate the long-term clinical outcomes of maxillary rehabilitation with
      dental implants after tumor resection. Patient satisfaction after maxillary
      reconstruction was also assessed with regard to function and comfort. MATERIALS
      AND METHODS: Over a 6-year period (2000-2005), 24 patients with maxillary tumors
      underwent resection with either immediate (n = 18) or delayed reconstruction or
      underwent prosthetic rehabilitation (n = 6).The patients received 88 implants in
      total, including 9 zygomatic and 79 conventional implants, for maxillary
      rehabilitation of the defective areas. RESULTS: Autogenous bone grafts were
      successful in all patients, although partial loss of the graft was observed in
      one patient who received an iliac graft. Patient follow-up was started at the
      point of the prosthetic loading of implants. The median treatment time was 99.1
      months (range:18-137 months). One patient died after 18 months of follow-up due
      to tumor recurrence, and two patients were lost to follow-up after 3 years of
      observation. Ten conventional dental implants were removed due to peri
      implantitis. Six patients chose implant-supported obturators. The cumulative
      survival and success rates of the implants were 88.6 and 86.3%, respectively.
      CONCLUSIONS: This study demonstrated that the rehabilitation of maxillary defects
      following tumor resection using implant-supported fixed prostheses with
      autogenous bone grafts or prosthetic rehabilitation is successful and is
      associated with high patient satisfaction. Oral function can be restored using
      dental implants for patients with maxillary defects.

PMID- 22882293
TI  - Governance mechanisms in the physician-patient relationship: a literature review
      and conceptual framework.
AB  - BACKGROUND: The physician-patient relationship is a critical component of the
      integrated approach to excellence in health-care delivery. Although commonly
      modelled within the boundaries of the agency theory and regarded as synonymous to
      an agent-principal interaction, there exists only a sparse understanding about
      the most effective ways of governing it. OBJECTIVE: This article undertakes a
      selective review of the growing body of research on the governance of the
      physician-patient relationship to discuss the current state of the knowledge in
      the field and suggest promising avenues for further exploration. FINDINGS: On the
      basis of an extensive analysis of the relevant literature, we identify two
      emerging streams of inquiry on the trust-based (i.e. trust and ethical oversight)
      and distrust-based (i.e. patient information-empowerment and decision-making
      authority) governance mechanisms of the physician-patient relationship and
      discuss the key findings within each stream. DISCUSSION: To conciliate the on
      going scholarly debate concerning the efficacy of trust- and distrust-based
      mechanisms, we draw the foundations of a conceptual framework which might serve
      as a guide for more integrative research endeavours on the governance of the
      physician-patient relationship.

PMID- 22882294
TI  - Congenital cytomegalovirus infection: patterns of fetal brain damage.
AB  - Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological
      dysfunction in the developing brain. This study analysed the different patterns
      of tissue damage, particularly in the brain, of fetuses with documented CMV
      infection. We studied 45 fetuses at 20-21 weeks of gestation with congenital CMV
      infection documented by invasive positive prenatal diagnosis. At the time of
      amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45
      fetuses (29%). Histological and immunohistochemical characterization was
      performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The
      different degrees of brain damage were correlated with tissue viral load,
      inflammatory response, placental functionality, and extramedullary
      haematopoiesis. Even though a high CMV load was detected in all amniotic fluids,
      brain infection occurred in only 62% of the fetuses and with different degrees of
      severity. Tissues with a low viral load showed a globally weak inflammatory
      response, and fetuses had only mild brain damage, whereas tissues with a high CMV
      load showed prominent infiltration of the activated cytotoxic CD8(+) T
      lymphocytes responsible for immune-mediated damage. Furthermore, severe placental
      infection was associated with diffuse villitis and necrosis, consistent with
      functional impairment and possible consequent hypoxic cerebral damage. Brain
      injury induced by CMV congenital infection may be the result of uncontrolled
      viral replication, immune-mediated damage by cytotoxic CD8(+) T-lymphocytes, and,
      in the presence of placental insufficiency, fetal hypoxia.

PMID- 22882296
TI  - Could the poor outcome of cerebral hemorrhage be improved by more aggressive
      first-line treatment?

PMID- 22882297
TI  - Mental health nurses' views of recovery within an acute setting.
AB  - How the principles of a recovery-oriented mental health service are incorporated
      in the day-to-day nursing practice of mental health nurses in inpatient settings
      is unclear. In this study, we interviewed 21 mental health nurses working in
      acute inpatient mental health units about a range of recovery-focused topics.
      Three overlapping themes were identified: (i) the perception of recovery; (ii)
      congruent humanistic approaches; and (iii) practical realities. Only four
      interviewees had some formal training about recovery. Most respondents recognize
      that positive attitudes, person-centred care, hope, education about mental
      illness, medication and side-effects, and the acknowledgement of individual
      recovery pathways are necessary to prevent readmission, and are central to a
      better life for people who live with a mental illness. This research supports the
      view that ideas and practices associated with the recovery movement have been
      adopted to some degree by nurses working at the acute end of the services
      continuum. However, most saw the recovery orientation as rhetoric rather than as
      an appropriately resourced, coordinated, and integrated program. These nurses,
      however, speak of much more detailed aspects of working with patients and being
      required to prepare them for the exigencies of living in the community post
      discharge.

PMID- 22882295
TI  - Stress-induced sensitization to cocaine: actin cytoskeleton remodeling within
      mesocorticolimbic nuclei.
AB  - This study investigated the consequence of repeated stress on actin cytoskeleton
      remodeling in the nucleus accumbens (NAc) and prefrontal cortex (Pfc), and the
      involvement of this remodeling in the expression of stress-induced motor cross
      sensitization with cocaine. Wistar rats were restrained daily (2 h) for 7 days
      and, 3 weeks later, their NAc and Pfc were dissected 45 min after acute saline or
      cocaine (30 mg/kg i.p.). F-actin, actin-binding proteins (ABP) and GluR1 were
      quantified by Western blotting, and dendritic spines and postsynaptic density
      (PSD) size measured by electron microscopy. In the NAc from the stress plus
      cocaine group we observed a decrease in the phosphorylation of two ABPs, cofilin
      and cortactin, and an increase in the PSD size and the surface expression of
      GluR1, consistent with a more highly branched actin cytoskeleton. The Pfc also
      showed evidence of increased actin polymerization after stress as an increase was
      observed in Arp2, and in the number of spines. Inhibiting actin cycling and
      polymerization with latrunculin A into the NAc, but not the Pfc, inhibited the
      expression of cross-sensitization to cocaine (15 mg/kg i.p.) and restored the
      expression of GluR1 to control levels. This study shows that a history of
      repeated stress alters the ability of a subsequent cocaine injection to modulate
      dendritic spine morphology, actin dynamics and GluR1 expression in the NAc.
      Furthermore, by regulating GluR1 expression in the NAc, elevated actin cycling
      contributes to the expression of cross-sensitization between stress and cocaine,
      while stress-induced changes in the Pfc were not associated with cross
      sensitization.

PMID- 22882298
TI  - Brain electrical activity after acute hippocampal stimulation in awake rats.
AB  - OBJECTIVE: We describe the electrocorticographic findings after hippocampal
      stimulation in normal awake rats. METHODS: Six male Wistar rats were implanted
      bilaterally with neocortical and hippocampal electrodes. The animals were
      submitted to hippocampal low- and high-frequency stimulation. RESULTS: Recruiting
      responses were seen in the ipsilateral hippocampus after unilateral low-frequency
      (6 Hz) hippocampal stimulation with low voltage (0.3 V). These recruiting
      responses could be seen at the contralateral hippocampus with slightly higher
      voltage (0.5 V) and over the ipsilateral neocortex with stimulation with 1.2 V.
      Bilateral neocortical recruiting responses were noted at stimuli voltage of 1.5
      V. There were no recruiting responses after high-frequency stimulation (130 Hz).
      A dorsal column (DC) shift, characterized by baseline oscillation without brain
      activity modification, was noted in all animals after hippocampal stimulation
      with frequency higher than 60 Hz. The increase of stimulation frequency from 6 to
      130 Hz (1.2 V, 300 u sec) showed progressive reduction in the amplitude and
      disappearance of the time-locked recruiting responses, especially from around 60
      Hz. CONCLUSIONS: Bilateral hippocampal and cortical recruiting responses were
      easily obtained in all animals after low-frequency hippocampal unilateral
      stimulation. High-frequency stimulation did not give rise to recruiting response,
      although a DC shift was noted. The fact that unilateral hippocampal stimulation
      might lead to bilateral limbic system modulation suggested that unilateral
      stimulation might be enough in many situations. Our findings suggested that high
      frequency stimulation was more likely to be effective than low-frequency
      stimulation regarding the potential inactivation of the hippocampus. These
      findings might prove relevant to the determination of the adequate parameters for
      stimulation using hippocampal deep brain stimulation (DBS) in the future. An
      increase in our knowledge on the physiologic mechanisms underlying DBS might be
      translated into more rational clinical approaches.

PMID- 22882299
TI  - Overactive bladder and sexual function: a nightmare couple.

PMID- 22882300
TI  - Population genetic structure of the tropical moss Acanthorrhynchium papillatum as
      measured with microsatellite markers.
AB  - Mosses and other bryophytes are vital components of forests, because they sustain
      a tremendous diversity of invertebrates and influence significant ecological
      functions. There have been few studies on moss population diversity in Southeast
      Asia, despite the escalating deforestation in this region of rich biodiversity.
      The genetic diversity of the tropical moss Acanthorrhynchium papillatum (Harv.)
      Fleisch., collected from forested areas in Singapore and Peninsular Malaysia, was
      elucidated using eight microsatellite markers developed for this species.
      Significant levels of allelic and haplotypic diversity were observed among clumps
      of the moss. Differences in allelic richness and genotypic diversity among the
      populations were higher in less disturbed forests compared to the more disturbed
      areas, suggesting that genetic diversity is affected by habitat quality. Genetic
      diversity levels within the clumps studied were low, indicating that vegetative
      reproduction was more important within clumps than sexual reproduction. However,
      multilocus genotypes of samples within the clumps studied were not all alike,
      providing evidence of microsatellite mutation or of occasional sexuality. Despite
      the isolation of populations, A. papillatum can introduce genetic variability by
      mutation among vegetatively propagated individuals. This study provides baseline
      information on the genetic diversity of A. papillatum tropical rain forests.

PMID- 22882302
TI  - Temporal dynamics and phylogenetic diversity of free-living and particle
      associated Verrucomicrobia communities in relation to environmental variables in
      a mesotrophic lake.
AB  - In the present study, the abundance and phylogenetic diversity of free-living and
      particle-associated Verrucomicrobia were investigated in a mesotrophic lake by
      quantitative PCR and sequencing of the 16S rRNA gene. The relative
      verrucomicrobial 16S rRNA gene abundance accounted for 0.02% to 1.98% of the
      particle-associated bacteria and 0.52% to 1.64% of the free-living bacteria. In
      total, 71 operational taxonomic units (OTUs) (n = 303 clones) were identified for
      particle-associated bacteria, and 59 OTUs (n = 292 clones) were identified for
      the free-living fraction. This study determined six new putative freshwater
      Verrucomicrobia clusters. Of these newly defined clusters, two were exclusively
      represented by particle-associated bacteria (FukuS27, BourFIV). The freshwater
      Verrucomicrobia clusters CRE-PA29, FukuN18 and CL120-10 appeared to be dominant,
      comprising 22.3%, 16.15% and 14.61% of the total retrieved OTUs, respectively.
      The seasonal dynamics of phytoplankton communities resulted in changes in the
      distinct bacterial phylotypes for both the particle-associated and free-living
      verrucomicrobial communities. According to canonical correspondence analysis, the
      diversity of the particle-associated verrucomicrobial communities appeared to be
      primarily influenced by phytoplankton richness, rotifer abundance and inorganic
      nutrients, whereas the free-living fraction was correlated with the biomass
      dynamics of some phytoplankton classes (Chlorophyceae, Chrysophaceae,
      Desmidiaceae and Zygnemataceae).

PMID- 22882301
TI  - Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and
      increases myocardial contractility.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic
      target for the treatment of heart failure. Herein we identify the selective
      serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2
      activity both in vitro and in living cells. In the crystal structure of the
      GRK2.paroxetine-Gbetagamma complex, paroxetine binds in the active site of GRK2
      and stabilizes the kinase domain in a novel conformation in which a unique
      regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes
      show increased isoproterenol-induced shortening and contraction amplitude in the
      presence of paroxetine, and pretreatment of mice with paroxetine before
      isoproterenol significantly increases left ventricular inotropic reserve in vivo
      with no significant effect on heart rate. Neither is observed in the presence of
      the SSRI fluoxetine. Our structural and functional results validate a widely
      available drug as a selective chemical probe for GRK2 and represent a starting
      point for the rational design of more potent and specific GRK2 inhibitors.

PMID- 22882303
TI  - Kodamaea ohmeri isolate from two immunocompromised patients: first report in
      Italy.
AB  - Kodamaea ohmeri is an unusual yeast-form fungus that has recently been identified
      as an important aetiological agent of fungaemia, endocarditis, cellulitis,
      funguria and peritonitis in immunocompromised patients. We present two new
      isolated of K. ohmeri. The microorganisms were identified by CHROMagar Candida
      medium, VitekII system and API ID32C. Biochemical identification of the two yeast
      isolates was confirmed by sequence analysis of the 26S ribosomal DNA. Antifungal
      susceptibility testing done by Sensititre YeastOne showed that the isolates were
      susceptible to amphotericin B, voriconazole and itraconazole. This work is the
      first report of isolation of K. ohmeri in immunocompromised patients in Italy.

PMID- 22882304
TI  - Key features of the seed germination response to high temperatures.

PMID- 22882305
TI  - Population genetic structure and its implications for adaptive variation in
      memory and the hippocampus on a continental scale in food-caching black-capped
      chickadees.
AB  - Food-caching birds rely on stored food to survive the winter, and spatial memory
      has been shown to be critical in successful cache recovery. Both spatial memory
      and the hippocampus, an area of the brain involved in spatial memory, exhibit
      significant geographic variation linked to climate-based environmental harshness
      and the potential reliance on food caches for survival. Such geographic variation
      has been suggested to have a heritable basis associated with differential
      selection. Here, we ask whether population genetic differentiation and potential
      isolation among multiple populations of food-caching black-capped chickadees is
      associated with differences in memory and hippocampal morphology by exploring
      population genetic structure within and among groups of populations that are
      divergent to different degrees in hippocampal morphology. Using mitochondrial DNA
      and 583 AFLP loci, we found that population divergence in hippocampal morphology
      is not significantly associated with neutral genetic divergence or geographic
      distance, but instead is significantly associated with differences in winter
      climate. These results are consistent with variation in a history of natural
      selection on memory and hippocampal morphology that creates and maintains
      differences in these traits regardless of population genetic structure and likely
      associated gene flow.

PMID- 22882306
TI  - Current trends of reproductive immunology practices in in vitro fertilization
      (IVF) - a first world survey using IVF-Worldwide.com.
AB  - PROBLEM: Reproductive immunology has evolved from basic research studies to
      clinical applications. In this study, we aim to investigate the actual
      application of reproductive immunology concepts and findings in clinical
      reproductive medicine such as recurrent pregnancy losses (RPL), repeated
      implantation failures (RIF), and failed in vitro fertilization (IVF) cycles.
      METHOD OF STUDY: A web-based survey was performed on IVF-Worldwide.com. Collected
      data were analyzed by the computerized software. RESULTS: A significant
      proportion of physicians recommend thrombophilia workups (86%), parental genetic
      study (79%), and immunologic evaluations (69%) to IVF candidates who have a
      history of RPL or chemical pregnancy losses. IVF physicians consider an
      immunologic workup when patients have two (30%) or three (21%) failed IVF cycles.
      Assays for anticardiolipin antibody, lupus anticoagulant, thyroid peroxidase
      antibody, and antinuclear antibody are the four most commonly ordered immunologic
      tests for RPL (88, 84, 50, 47% each) and RIF (68, 63, 38, 38% each). Cellular
      immune evaluations, such as NK assay, human leukocyte antigen study, Th1/Th2
      study or immunophenotype assay, are less commonly ordered. CONCLUSIONS:
      Reproductive immunology principles have been applied to the clinical management
      of RPL, RIF, and failed IVF cycles, and a significant proportion of IVF
      physicians acknowledge the importance of immunologic alterations with
      reproductive outcomes.

PMID- 22882307
TI  - Incidence and risk of hypertension with vandetanib in cancer patients: a
      systematic review and meta-analysis of clinical trials.
AB  - AIM: To perform a systematic review and meta-analysis of published clinical
      trials to determine incidence rate and overall risk of hypertension with
      vandetanib in cancer patients. METHODS: A comprehensive literature search for
      studies published up to March 2012 was performed. Summary incidence rates,
      relative risk (RR), and 95% confidence intervals (CI) were calculated employing
      fixed- or random-effects models depending on the heterogeneity of the included
      trials. RESULTS: A total of 11 trials with 3154 patients were included for the
      meta-analysis. The summary incidences of all-grade and high-grade hypertension in
      patients with cancer were 24.2% [95% confidence interval (CI), 18.1-30.2%] and
      6.4% (95% CI, 3.3-9.5%), respectively. Subgroup analysis demonstrated that the
      pooled incidences of all-grade and high-grade hypertension were 21.8% [95% CI, 15
      30.5%] and 7.6% (95% CI, 2.8-18.8%), respectively, among non-small-cell lung
      cancer (NSCLC) patients, and 32.1% (95% CI: 27.3-37.3%) and 8.8% (5.9%-12.9%),
      respectively, among MTC patients, and 15.4 (95% CI: 3.2-33.7%) and 3.4% (95% CI:
      1%-11.1%) respectively, among non-MTC/NSCLC tumors patients. Furthermore,
      vandetanib was associated with a significant increased risk of all-grade
      hypertension (RR 5.1, 95% CI: 3.76-6.92, P = 0.000) and high-grade hypertension
      (RR 8.06, 95% CI: 3.41-19.04, P = 0.000) in comparison with controls.
      CONCLUSIONS: There is a significant risk of developing hypertension in cancer
      patients receiving vandetanib. Appropriate monitoring and treatment is strongly
      recommended to prevent cardiovascular complications.

PMID- 22882308
TI  - Arginine vasopressin-dependent and AVP-independent mechanisms of renal fluid
      absorption during thirsting despite glucocorticoid-mediated vasopressin
      suppression.
AB  - OBJECTIVE: Glucocorticoids seem to modify the release and effects of plasma
      arginine vasopressin (pAVP). However, underlying processes are not well
      understood. This study aimed to evaluate the mechanism of the modulating effects
      of glucocorticoids on pAVP and renal water reabsorption. DESIGN: Fluid
      deprivation tests were performed without (d0) and after one (d1) and five days
      (d5) of oral prednisolone (Pred) pretreatment in a dosage relevant to drug
      therapy (30 mg/day). PATIENTS: Twelve healthy male volunteers participated in
      this trial. MEASUREMENTS: Plasma and urinary osmolality, pAVP, renin,
      aldosterone, plasma atrial natriuretic peptide (ANP) as well as urinary secretion
      of aquaporin-2 (AQP2) and prostaglandin E(2) (PGE2) were analysed. RESULTS: An
      appropriate rise in pAVP was observable during thirsting (P < 0.001), which was
      absent after Pred pretreatment. However, the plasma and urinary osmolality after
      Pred treatment did not differ when compared with the basal thirsting test.
      Unchanged urinary AQP2 excretion suggests AVP-independent mechanisms of renal
      fluid reabsorption. Plasma renin concentration as well as ANP was substantially
      increased after Pred intake at d1 and d5 (both P < 0.05), which may mediate such
      AVP-independent mechanisms. Urinary PGE2 secretion was not influenced by Pred
      pretreatment, making a PGE2-mediated effect on renal AQP2 translocation and water
      permeability unlikely. Increased efficacy of exogenous desmopressin at d1 and d5
      indicates also a relative increase in AVP sensitivity of the tubular cells after
      Pred intake. CONCLUSIONS: The here presented data are compatible with an
      increased AVP sensitivity and a partially AVP-independent regulation of AQP2
      translocation and renal fluid reabsorption during glucocorticoid treatment.

PMID- 22882309
TI  - Bone histomorphometry using free and commonly available software.
AB  - AIMS: Histomorphometric analysis is a widely used technique to assess changes in
      tissue structure and function. Commercially available programs that measure
      histomorphometric parameters can be cost-prohibitive. In this study, we compared
      an inexpensive method of histomorphometry to a current proprietary software
      program. METHODS AND RESULTS: Image J and Adobe Photoshop((r)) were used to
      measure static and kinetic bone histomorphometric parameters. Photomicrographs of
      Goldner's trichrome-stained femurs were used to generate black-and-white image
      masks, representing bone and non-bone tissue, respectively, in Adobe
      Photoshop((r)) . The masks were used to quantify histomorphometric parameters
      (bone volume, tissue volume, osteoid volume, mineralizing surface and interlabel
      width) in Image J. The resultant values obtained using Image J and the
      proprietary software were compared and differences found to be statistically non
      significant. CONCLUSIONS: The wide-ranging use of histomorphometric analysis for
      assessing the basic morphology of tissue components makes it important to have
      affordable and accurate measurement options available for a diverse range of
      applications. Here we have developed and validated an approach to
      histomorphometry using commonly and freely available software that is comparable
      to a much more costly, commercially available software program.

PMID- 22882310
TI  - Immediate fixed rehabilitation of the edentulous maxilla: a prospective clinical
      and radiological study after 3 years of loading.
AB  - PURPOSE: The aim of this study was to prospectively evaluate the clinical and
      radiographic outcomes of immediate full-arch fixed maxillary prosthesis supported
      by two axial and four tilted implants after 3 years of loading. MATERIALS AND
      METHODS: Thirty-two patients with atrophic maxilla were consecutively enrolled
      and treated. Each patient received a fixed full-arch maxillary rehabilitation
      supported by four tilted implants that engaged the posterior and the anterior
      sinus walls and two axial anterior implants. A total of 192 implants (30
      Branemark System MK IV and 162 NobelSpeedy Groovy, Nobel Biocare AB, Goteborg,
      Sweden) were inserted and immediately loaded. The definitive restorations were
      placed 6 months later, and follow-up visits were scheduled every 6 months. During
      follow-ups, marginal bone loss (MBL), plaque and bleeding scores, and patient's
      satisfaction were recorded. RESULTS: All patients reached at least 3-year follow
      up examination (range 36-78, average 55.53 months). Two tilted implants failed
      before delivering the definitive restoration, resulting in a cumulative survival
      rate of 98.96%. All final prostheses were stable and functional, resulting in a
      cumulative survival and success rate of 100%. At the 3-year follow-up there was
      no significant difference in MBL between axial (1.55 +/- 0.31 mm) and tilted
      implants (1.46 +/- 0.19 mm) (p = .05). Plaque and bleeding scores decreased over
      time, while patient's satisfaction in both aesthetics and function increased.
      CONCLUSIONS: Implants placement with this configuration could be considered a
      predictable and cost- and time-effective alternative approach for the immediate
      restoration of the edentulous maxilla, avoiding bone grafting procedures, even
      with a medium-term follow-up.

PMID- 22882311
TI  - Answer to 'Toxic epidermal necrolysis with failure of re-epithelialization. Could
      umbilical cord mesenchymal stem cell transplantation have a role?'.

PMID- 22882313
TI  - The Brain and Obesity Lectures Series--the beginning of a new field?

PMID- 22882312
TI  - Childhood obesity and sleep: relatives, partners, or both?--a critical
      perspective on the evidence.
AB  - In modern life, children are unlikely to obtain sufficient or regular sleep and
      waking schedules. Inadequate sleep affects the regulation of homeostatic and
      hormonal systems underlying somatic growth, maturation, and bioenergetics.
      Therefore, assessments of the obesogenic lifestyle, including as dietary and
      physical activity, need to be coupled with accurate evaluation of sleep quality
      and quantity, and coexistence of sleep apnea. Inclusion of sleep as an integral
      component of research studies on childhood obesity should be done as part of the
      study planning process. Although parents and health professionals have quantified
      normal patterns of activities in children, sleep has been almost completely
      overlooked. As sleep duration in children appears to have declined, reciprocal
      obesity rates have increased. Also, increases in pediatric obesity rates have
      markedly increased the risk of obstructive sleep apnea syndrome (OSAS) in
      children. Obesity and OSAS share common pathways underlying end-organ morbidity,
      potentially leading to reciprocal amplificatory effects. The relative paucity of
      data on the topics covered in the perspective below should serve as a major
      incentive toward future research on these critically important concepts.

PMID- 22882314
TI  - Ultrastructural and molecular confirmation of the trichodysplasia spinulosa
      associated polyomavirus in biopsies of patients with trichodysplasia spinulosa.
AB  - Trichodysplasia spinulosa (TS) is a rare and only recently characterized
      cutaneous disease occurring in immunocompromised patients. The disease is
      characterized by spiny follicular papules on clinical examination and by the
      presence of viral inclusions at ultrastructural examination. In the last year,
      this virus has been identified as a new member of the polyomavirus family and
      designated as TS-associated polyomavirus (TSPyV). We report two organ transplant
      patients with this disease in which we were able to identify the TSPyV at
      ultrastructural and molecular level from formalin-fixed paraffin-embedded
      biopsies of lesional skin. Similar to prior described cases, the patients
      presented with follicular papules which were concentrated on the central face and
      associated with alopecia. Histopathology of both cases showed dilated follicular
      infundibula plugged with cornified eosinophilic cells containing large
      trichohyaline granules. Transmission electron microscopy on paraffin-embedded
      tissue in case 1 showed 28-nm intracellular viral particles morphologically
      consistent with polyoma virus. For both cases the presence of TSPyV was confirmed
      by polymerase chain reaction with virus-specific primers followed by
      identification by direct sequencing. These two cases show the presence of the
      newly described TSPyV in TS further establishing its association with this
      distinctive disease.

PMID- 22882315
TI  - Late Devonian marine anoxia challenged by benthic cyanobacterial mats.
AB  - Mass occurrence of benthic cyanobacterial mats in a sequence of Late Devonian
      black shales and bituminous limestones of the Holy Cross Mts. (central Poland),
      enclosing the famous Kellwasser and Hangenberg extinction horizons, is reported.
      The microbiota forming the mats is compared with some modern benthic
      chroococcalean cyanobacteria. Similarly to their extant counterparts, the
      Devonian cyanobacteria must had been phototrophic and oxygenic aerobes which
      could, however, tolerate slightly sulfidic conditions characterizing the near
      bottom waters of the Late Devonian epicontinental sea. The cyanobacterial mats
      successfully colonized the oxygen-deficient and H(2)S-enriched seabed otherwise
      unfavorable for most other benthic biota. The redox state of this sluggish Late
      Devonian sea, ascribed previously mostly to anoxic or euxinic conditions, is
      reassessed as probably pulsating between anoxic, dysoxic, and weakly oxic
      conditions. The redox state was dependent on the rate of oxygen production by the
      cyanobacterial mats, the intensity of H(2)S emissions from the decaying mat
      biomass, and the rate of planktonic production.

PMID- 22882316
TI  - The clinical significance of platelet counts in the first 24 hours after severe
      injury.
AB  - BACKGROUND: Admission platelet (PLT) counts are known to be associated with all
      cause mortality for seriously injured patients admitted to a trauma center. The
      course of subsequent PLT counts, their implications, and the effects of PLT
      therapy are less well known. STUDY DESIGN AND METHODS: Trauma center patients who
      were directly admitted from the scene of injury, received 1 or more units of
      uncrossmatched red blood cells in the first hour of care, survived for at least
      15 minutes, and had a PLT count measured in the first hour were analyzed for the
      association of their admission and subsequent PLT counts in the first 24 hours
      with injury severity and hemorrhagic and central nervous system (CNS) causes of
      in-hospital mortality. RESULTS: Over an 8.25-year period, 1292 of 45,849 direct
      trauma admissions met entry criteria. Admission PLT counts averaged 228*10(9) +/
      90*10(9) /L and decreased by 104*10(9) /L by the second hour and 1*10(9) /L each
      hour thereafter. The admission count was not related to time to admission. Each 1
      point increase in the injury severity score was associated with a 1*10(9) /L
      decrease in the PLT count at all times in the first 24 hours of care. Admission
      PLT counts were strongly associated with hemorrhagic and CNS injury mortality and
      subsequent PLT counts. Effects of PLT therapy could not be ascertained.
      DISCUSSION: Admission PLT counts in critically injured trauma patients are
      usually normal, decreasing after admission. Low PLT counts at admission and
      during the course of trauma care are strongly associated with mortality.

PMID- 22882317
TI  - Local plant density, pollination and trait-fitness relationships in a perennial
      herb.
AB  - Both differences in local plant density and phenotypic traits may affect
      pollination and plant reproduction, but little is known about how density affects
      trait-fitness relationships via changes in pollinator activity. In this study we
      examined how plant density and traits interact to determine pollinator behaviour
      and female reproductive success in the self-incompatible, perennial herb Phyteuma
      spicatum. Specifically, we hypothesised that limited pollination service in more
      isolated plants would lead to increased selection for traits that attract
      pollinators. We conducted pollinator observations and assessed trait-fitness
      relationships in a natural population, whose individuals were surrounded by a
      variable number of inflorescences. Both local plant density and plant phenotypic
      traits affected pollinator foraging behaviour. At low densities, pollinator
      visitation rates were low, but increased with increasing inflorescence size,
      while this relationship disappeared at high densities, where visitation rates
      were higher. Plant fitness, in terms of seed production per plant and per
      capsule, was related to both floral display size and flowering time. Seed
      production increased with increasing inflorescence size and was highest at peak
      flowering. However, trait-fitness relationships were not density-dependent, and
      differences in seed production did not appear to be related to differences in
      pollination. The reasons for this remain unclear, and additional studies are
      needed to fully understand and explain the observed patterns.

PMID- 22882318
TI  - Macular oedema due to letrozole: a first case report.
AB  - A 72-year-old woman presented with unexplained, progressive, painless visual loss
      in the right eye during the past six months. At presentation visual acuity (VA)
      was 3/60 in the right eye and 6/6 in the left eye. Anterior segment examination
      and intraocular pressures were normal. Dilated fundoscopy revealed significant
      macular oedema in the right eye and a normal fundus appearance in the left eye.
      Her medical history was noteworthy for breast ductal carcinoma in situ, for which
      she had undergone right mastectomy three years earlier. She had not received
      chemotherapy or radiotherapy but she had been under treatment with letrozole 2.5
      mg/day over the past three years. She did not receive any other medication.
      Optical coherence tomography showed intraretinal fluid and a significant increase
      in retinal thickness in the foveal and parafoveal areas, while fluorescein
      angiography detected foveal hyperfluorescence and leakage of the dye in the late
      phase. Multifocal electroretinogram showed a decreased response in both eyes. In
      suspicion of letrozole-related retinopathy, the patient was advised to stop the
      medication. The patient agreed to receive an intravitreal injection of 0.05
      ml/0.5 mg ranibizumab. One month later, VA in the right eye was 6/9 and macular
      oedema had apparently improved. This is the first reported case of letrozole
      associated macular oedema treated with intravitreal ranibizumab.

PMID- 22882319
TI  - The relevance of patient-reported outcomes in a grass pollen immunotherapy trial
      in children and adolescents with rhinoconjunctivitis.
AB  - BACKGROUND: Patient-reported outcomes (PROs) are the only instruments available
      to assess the efficacy of an intervention in patients with allergic
      rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is
      now recommended to use not only PROs focusing at classical symptoms, but also
      health-related quality of life (HRQL) instruments in immunotherapy trials.
      METHODS: A previously published immunotherapy trial in children and adolescents
      (6-18 yr) with hay fever provided us with data to assess the relevance of two of
      these additional outcome measures, the disease-specific rhinoconjunctivitis
      quality of life questionnaire (RQLQ) and the generic COOP/WONCA-charts (CWC). A
      PRO was considered relevant if it was responsive to pollen exposure and at least
      had a moderate correlation with the classical symptoms of allergic
      rhinoconjunctivitis. Furthermore, we evaluated a post-season PRO, that is, a
      global assessment of symptoms (GAS). This assessment is used in clinical trials
      as a tool for selecting participants with sufficient symptoms and in daily
      practice to evaluate the patient's complaints during the preceding season. We
      assessed the correlation of this retrospective score with the actual symptoms
      during the previous pollen season. RESULTS: Data from 36 children and 63
      adolescents were analysed. On the basis of the total scores of the paediatric and
      adolescent version of the RQLQ, both questionnaires were considered relevant as
      they were responsive to exposure and showed a moderate to strong correlation with
      the rhinoconjunctivitis symptoms. However, in both children and adolescents, 40%
      of the RQLQ items were not relevant according to our definition. The CWC as a
      whole and the separate charts appear less relevant because of the weak
      correlations with the daily symptom score from the diary. The correlation between
      our post-season GAS and the in season daily symptom score was weak. CONCLUSION:
      The paediatric and adolescent RQLQ are relevant, but could be shortened as they
      contain a substantial number of irrelevant items. The CWC are not relevant in the
      monitoring of children and adolescents with allergic rhinoconjunctivitis caused
      by grass pollen. The retrospective GAS does not sufficiently reflect the actual
      symptoms during the preceding season.

PMID- 22882320
TI  - Coxsackievirus B1 peritonitis in a patient treated with continuous ambulatory
      peritoneal dialysis: a case report and brief review of the literature.
AB  - We report a case of viral peritonitis caused by coxsackievirus B1 in a 79-year
      old male undergoing continuous ambulatory peritoneal dialysis (CAPD), and review
      the English language literature. Clinicians should be aware of viral peritonitis
      in patients on CAPD presenting with a viral syndrome and mononuclear peritoneal
      dialysis effluent. Currently, viral diagnostic tests are available to confirm the
      diagnosis and avoid unnecessary treatment with antibiotics.

PMID- 22882321
TI  - Evaluating the cost-effectiveness of laparoscopic adjustable gastric banding
      versus standard medical management in obese patients with type 2 diabetes in the
      UK.
AB  - AIM: To evaluate the cost-effectiveness of laparoscopic adjustable gastric
      banding (LAGB) versus standard medical management (SMM) in obese patients with
      type 2 diabetes from a UK healthcare payer perspective. METHODS: A validated
      computer model of diabetes was used to project outcomes reported from a
      randomized clinical trial of LAGB versus SMM in obese patients with type 2
      diabetes. Two-year follow-up data from the trial were projected over a 40-year
      time horizon and cost-effectiveness was assessed from the perspective of the
      National Health Service. Future costs and clinical outcomes were discounted at
      3.5% annually and all costs were reported in 2010 pounds sterling. A series of
      sensitivity analyses were performed. RESULTS: LAGB was associated with benefits
      in HbA1c, systolic blood pressure, body mass index and serum lipid
      concentrations, which led to significant increases in discounted life expectancy
      (an increase of 0.64 years) and quality-adjusted life expectancy (an increase of
      0.92 quality-adjusted life years, QALYs) and reduced incidence of diabetes
      complications relative to SMM. Treatment costs in the LAGB arm increased by 4552
      Great British Pounds (GBP), but this was partially offset by cost savings
      resulting from a reduction in the incidence of all modelled diabetes
      complications. The incremental cost-effectiveness ratio of GBP 3602 per QALY in
      the base case fell well below commonly quoted willingness-to-pay thresholds in
      the UK setting. CONCLUSIONS: On the basis of data from a recent randomized
      controlled trial, LAGB is likely to be considered cost-effective from the
      healthcare payer perspective when compared with SMM of obesity in patients with
      type 2 diabetes in the UK setting.

PMID- 22882322
TI  - Rising to the challenge.

PMID- 22882323
TI  - Association between bronchopulmonary dysplasia and MBL2 and IL1-RN polymorphisms.
AB  - BACKGROUND: The imbalance between pro-inflammatory and anti-inflammatory
      cytokines may play a role in the development of bronchopulmonary dysplasia (BPD)
      in preterm infants. Mannose binding lectin (MBL) codon 54 and interleukin 1
      receptor antagonist gene (IL1-RN) polymorphisms cause genetic predisposition to
      increased risk of infection and inflammation, therefore may increase the risk of
      BPD. The aim of this study was to investigate the relationship between MBL, IL1
      RN gene polymorphisms and BPD development in preterm infants. METHODS: MBL codon
      54 and IL1-RN polymorphisms were studied in 71 infants who were born at <32 weeks
      of gestation, with the diagnosis of BPD (group 1) and in a control group of
      preterm infants without BPD (group 2). RESULTS: IL1-RN and MBL2 variant genes
      were closely associated with increased risk of BPD (both P < 0.001) together with
      significantly lower birthweight (P < 0.001 and P = 0.001, respectively), lower 5
      min Apgar scores (P = 0.009 for both genes) and increased neonatal infection rate
      (P < 0.001 and P < 0.009, respectively). The IL1 RN 1/1 genotype was protective
      (odds ratio [OR], 0.075; 95% confidence interval [CI]: 0.019-0.76) while the IL1
      RN 2/2 genotype increased the risk for BPD (OR, 11.7; 95%CI: 1.3-103.6). The MBL
      AA genotype was protective against BPD (OR, 0.066; 95%CI: 0.02-0.2) whereas the
      MBL-BB genotype increased the susceptibility for the development of BPD (OR,
      23.8; 95%CI: 2.8-200.6). CONCLUSION: MBL and IL 1 RN polymorphisms are closely
      related to low birthweight and increase the risk of neonatal sepsis and BPD
      development in preterm infants.

PMID- 22882324
TI  - Multiphoton laser tomography and fluorescence lifetime imaging of basal cell
      carcinoma: morphologic features for non-invasive diagnostics.
AB  - Multiphoton laser tomography (MPT) combined with fluorescence lifetime imaging
      (FLIM) is a non-invasive imaging technique, which gives access to the cellular
      and extracellular morphology of the skin. The aim of our study was to assess the
      sensitivity and specificity of MPT/FLIM descriptors for basal cell carcinoma
      (BCC), to improve BCC diagnosis and the identification of tumor margins. In the
      preliminary study, FLIM images referring to 35 BCCs and 35 healthy skin samples
      were evaluated for the identification of morphologic descriptors characteristic
      of BCC. In the main study, the selected parameters were blindly evaluated on a
      test set comprising 63 BCCs, 63 healthy skin samples and 66 skin lesions.
      Moreover, FLIM values inside a region of interest were calculated on 98 healthy
      skin and 98 BCC samples. In the preliminary study, three epidermal descriptors
      and 7 BCC descriptors were identified. The specificity of the diagnostic criteria
      versus 'other lesions' was extremely high, indicating that the presence of at
      least one BCC descriptor makes the diagnosis of 'other lesion' extremely
      unlikely. FLIM values referring to BCC cells significantly differed from those of
      healthy skin. In this study, we identified morphological and numerical
      descriptors enabling the differentiation of BCC from other skin disorders and its
      distinction from healthy skin in ex vivo samples. In future, MPT/FLIM may be
      applied to skin lesions to provide direct clinical guidance before biopsy and
      histological examination and for the identification of tumor margins allowing a
      complete surgical removal.

PMID- 22882325
TI  - Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase gene
      mutations in iranian women with polycystic ovary syndrome.
AB  - PROBLEM: Mutations in genes related to thrombophilia and hypofibrinolysis have
      been associated with recurrent pregnancy loss (RPL) and polycystic ovary syndrome
      (PCOS). METHODS: Using PCR-RFLP, we investigated the frequencies of MTHFR (A1298C
      and C677T) as well as PAI-1 (-675 4G/5G) gene polymorphisms in 177 RPL and 100
      control women. RPL women were stratified into 38 women with PCOS (RPL-PCOS), 33
      with ovarian PCO (RPL-ovarian PCO), and 106 without PCOS (RPL). RESULTS: RPL, RPL
      PCOS, and RPL-ovarian PCO groups showed significantly higher frequencies of MTHFR
      A1298C (P < 0.001) and PAI-1 4G/5G (P < 0.001) mutations than the controls. No
      significant differences were found between the RPL groups. The respective odds
      ratios (OR) for bearing MTHFR (A1298C, C677T) and PAI-1 (4G/5G) gene mutations
      were 33.9-, 2.2-, and 5.2-fold higher in RPL, 66.3-, 6.7-, and 2.8-fold higher in
      RPL-PCOS, and 27.3-, 1.9-, and 3.9-fold higher in RPL-ovarian PCO women than
      those in controls. CONCLUSION: Our results showed the significance of MTHFR
      A1298C and PAI-1 4G/5G mutations in Iranian women suffering from RPL with and
      without PCOS.

PMID- 22882326
TI  - FOXE1 polymorphisms are associated with familial and sporadic nonmedullary
      thyroid cancer susceptibility.
AB  - OBJECTIVE: FOXE1 is a transcription factor required for thyroid differentiation
      and function. FOXE1 locus polymorphisms (chromosome 9q22.33) were recently
      associated with increased sporadic thyroid cancer risk. In this study, we aimed
      to investigate the association of FOXE1 variants with nonmedullary thyroid cancer
      (NMTC), in both sporadic and familial (FNMTC) cases from the Portuguese
      population. DESIGN AND METHODS: Nine variants located at the FOXE1 locus were
      sequenced in genomic DNA from 60 FNMTC probands and 80 patients with sporadic
      NMTC. Alleles were tested for association with thyroid cancer, against 130
      healthy matched Portuguese controls. RESULTS: All variants were significantly
      associated with increased thyroid cancer risk when combining familial and
      sporadic cases (OR range = 1.62-2.58). In particular, two reported risk variants
      were associated with the disease: rs965513 (allele A) with familial (OR = 2.30,
      95% CI = 1.48-3.59, P = 0.0002) and sporadic (OR = 2.81, 95% CI = 1.87-4.22, P <
      0.0001) NMTC and rs1867277 (allele A) with the sporadic (OR = 1.76, 95% CI = 1.18
      2.62, P = 0.0052) and combined NMTC cases (OR = 1.70, 95% CI = 1.21-2.40, P =
      0.0022). Interestingly, we also identified association of FOXE1 polyalanine tract
      expansions (>14 alanines) with thyroid cancer risk, in both familial (OR = 2.56,
      95% CI = 1.64-4.01, P < 0.0001) and sporadic (OR = 2.44, 95% CI = 1.61-3.68, P <
      0.0001) cases. CONCLUSIONS: We found compelling evidence of association between
      FOXE1 variants and thyroid cancer risk in the Portuguese population. To our
      knowledge, this is the first study supporting the association of this locus with
      both sporadic and familial NMTC susceptibility.

PMID- 22882327
TI  - Late-onset myasthenia not on the increase: a nationwide register study in
      Denmark, 1996-2009.
AB  - BACKGROUND: An increase in late-onset myasthenia gravis (MG) has been reported.
      There are few large population-based studies over longer periods of time
      reflecting recent developments in MG incidence. METHODS: We identified a
      nationwide cohort of patients with incident myasthenia in Denmark in 1996-2009.
      We used a validated algorithm to track subjects based on a combination of
      diagnosis and prescription (pyridostigmine) data from nationwide registers.
      Patients with myasthenia were classified into early onset (<50 years old) and
      late onset (50+ years). We calculated incidence rates (IRs) and corresponding 95%
      confidence intervals. RESULTS: We identified 693 patients (362 women) with
      incident MG in the study period corresponding to an IR of 9.2 per million person
      years (8.5-9.9). Overall, 207 (29.9%) were classified as early-onset and 486
      (70.1%) as late-onset MG. Women predominated in the early-onset group (70.5%),
      but not in the late-onset group (44.4%). The incidence rate of early-onset MG was
      4.2 (3.6-4.8) and late-onset MG 18.9 (17.3-20.7) per million person-years and it
      did not vary over time in the study period (P-values for trend 0.54 and 0.15,
      respectively). CONCLUSION: Late-onset MG comprised a large proportion of all
      incident cases in Denmark, was more common in men than women, and occurred with a
      stable incidence in the 14-year study period. Therefore, we speculate whether
      previous reports of a rise in late-onset MG reflect a non-biological phenomenon,
      that is, a gradual improvement in the diagnosis of MG in this age group in
      previous years.

PMID- 22882328
TI  - Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative
      diagnosis of brain tumors.
AB  - Intraoperative diagnosis plays an important role in accurate sampling of brain
      tumors, limiting the number of biopsies required and improving the distinction
      between brain and tumor. The goal of this study was to evaluate dye-enhanced
      multimodal confocal imaging for discriminating gliomas from nonglial brain tumors
      and from normal brain tissue for diagnostic use. We investigated a total of 37
      samples including glioma (13), meningioma (7), metastatic tumors (9) and normal
      brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL
      aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal
      images were acquired using a custom-built microscope. After imaging, tissue was
      formalin fixed and paraffin embedded for standard neuropathologic evaluation.
      Thirteen pathologists provided diagnoses based on the multimodal confocal images.
      The investigated tumor types exhibited distinctive and complimentary
      characteristics in both the reflectance and fluorescence responses. Images showed
      distinct morphological features similar to standard histology. Pathologists were
      able to distinguish gliomas from normal brain tissue and nonglial brain tumors,
      and to render diagnoses from the images in a manner comparable to haematoxylin
      and eosin (H&E) slides. These results confirm the feasibility of multimodal
      confocal imaging for intravital intraoperative diagnosis.

PMID- 22882329
TI  - Cytomegalovirus-induced cutaneous microangiopathy manifesting as lower limb
      ischemia in a human immunodeficiency virus-infected patient.
AB  - Cutaneous infections by cytomegalovirus (CMV) are rare and often difficult to
      diagnose both clinically and histopathologically. A wide range of different
      clinical manifestations have been described in the literature, especially in
      immunosuppressed patients. CMV-induced thrombosis has also been reported in these
      patients, and various mechanisms have been proposed to explain the role of CMV in
      the thrombotic process, including direct damage of the endothelial cells,
      activation of coagulation factors and inducing the production of antiphospholipid
      antibodies. We present the case of a human immunodeficiency virus (HIV)-infected
      woman who developed distal ischemic lesions of the lower extremities during a
      generalized CMV infection. We discuss the role of CMV and antiphospholipid
      antibodies in the pathogenesis of thrombosis in immunosuppressed patients.

PMID- 22882330
TI  - Yeasts from glacial ice of Patagonian Andes, Argentina.
AB  - Glacial ice and snow are known habitats for cold-adapted microorganisms. Research
      on cold-adapted yeast biodiversity from Perito Moreno and Mount Tronador glaciers
      (Patagonia, Argentina), and production of extracellular enzymatic activity at low
      temperatures (5 and 18  degrees C), was performed and described in this study.
      Ninety percent (90%) of the isolates were basidiomycetous; 16 genera and 29
      species were identified. Twenty-five percent (25%) of total isolates corresponded
      to psychrophilic yeasts, whereas 75% were psychrotolerant yeasts. Eighty-five
      percent (85%) of all isolates had at least one enzymatic activity. Multiple
      correspondence analysis and cluster classification revealed a relationship
      between certain genera and some enzymatic activities. Cold-adapted yeast isolates
      were able to hydrolyze natural compounds (casein, lipids, starch, pectin, and
      carboxymethylcellulose) at low temperatures, suggesting a significant ecological
      role of these organisms as organic matter decomposers and nutrient cyclers. These
      yeasts are especially relevant for metabolic and ecological studies, as well as
      for yeast-based biotechnological process at low temperatures.

PMID- 22882331
TI  - The Aarhus Neuromodulation Database.
AB  - OBJECTIVES: ?? Spinal cord stimulation (SCS) is increasingly gaining widespread
      use as a treatment for chronic pain. A widely used electronic registry could play
      a pivotal role in improving this complex and cost-??intensive treatment. We aimed
      to construct a comprehensive, universally available data base for SCS. MATERIALS
      AND METHODS: ?? The design considerations behind a new online data base for SCS
      are presented; basic structure, technical issues, research applications, and
      future perspectives are described. RESULTS: ?? The Aarhus Neuromodulation
      Database covers core SCS treatment parameters, including procedure-??related
      details and complications, and features recording of key success parameters such
      as pain intensity, work status, and quality of life. It combines easy access to
      patient information with exhaustive data extraction options, and it can readily
      be adapted and expanded to suit different needs, including other neuromodulation
      treatment modalities. CONCLUSIONS: ?? We believe that the data base described in
      this article offers a powerful and versatile data collection tool suited for both
      clinicians and researchers in the field. The basic data base structure is
      immediately available on a no?-cost basis, and we invite our colleagues to make
      use of the data base as part of the efforts to further the field of
      neuromodulation.

PMID- 22882332
TI  - Mini-invasive osteotome sinus floor elevation in partially edentulous atrophic
      maxilla using reduced length dental implants: interim results of a prospective
      study.
AB  - PURPOSE: The purpose of this prospective study was to investigate the clinical
      success of a treatment protocol for the rehabilitation of edentulous posterior
      maxilla consisting of the positioning of short implants in combination with
      transcrestal sinus lifting, with the adjunct of pure (leukocyte-free) platelet
      rich plasma, in order to reducing the risk of membrane perforation and other
      surgical complications. MATERIALS AND METHODS: A total of 25 patients (65
      implants) were treated. Pure platelet-rich plasma was used in the sinus membrane
      lifting procedure. Implants of 8.5 mm length or shorter were splinted through the
      prosthetic rehabilitation with one or more implants longer than 10 mm. RESULTS:
      After a follow-up period ranging from 12 to 19 months (mean 14.4 months) after
      prosthetic loading, 23 patients (60 implants) were evaluated. Overall implant
      success and survival rates were 100% at 1 year follow-up visit. All prosthetic
      rehabilitations were successful and in function. After 1 year of loading, peri
      implant bone loss averaged 0.34 +/- 0.21 mm for 8.5 mm or shorter implants (n =
      25) and 0.36 +/- 0.30 mm for longer implants (n = 35) (overall mean 0.35 +/- 0.25
      mm) without significant difference between the two groups (p = 0.23).
      CONCLUSIONS: The proposed treatment protocol is a viable option for the
      rehabilitation of edentulous posterior atrophic maxilla.

PMID- 22882334
TI  - Brain stimulation in neurology and psychiatry: perspectives on an evolving field.

PMID- 22882333
TI  - Benzodiazepine harm: how can it be reduced?
AB  - The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle
      relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively
      and cognitive and psychomotor impairment objectively. Complex skills such as
      driving can be compromised. Paradoxical excitement can have forensic
      implications. Long term use beyond the licensed durations is common but both
      efficacy and adverse effects associated with this have been poorly documented.
      Withdrawal and dependence have excited particular concern, and even polemic.
      Perhaps a third of long term (beyond 6  months) users experience symptoms and
      signs on attempting to withdraw - anxiety, insomnia, muscle spasms and tension
      and perceptual hypersensitivity. Uncommonly, fits or a psychosis may supervene.
      The patterns following withdrawal vary widely. The usual method of withdrawal is
      slow tapering but it may not obviate the problems completely. BZDs are also drugs
      of abuse either on their own or in conjunction with opioids and stimulants.
      Claims have been made that the use of BZDs is associated with increased
      mortality. This is a concern in view of the widespread usage of these drugs,
      particularly in the elderly. All of these factors impinge on the risk : benefit
      ratio and the severity of the indications. Harm reduction should focus on choice
      of alternative treatments both psychological and pharmacological. Guidelines
      emphasise that BZDs are not drugs of first choice and should only be used short
      term. Schedules are available to educate about methods of withdrawal in current
      users, emphasising the slow rate of taper. General principles of harm
      minimization in the addiction field are appropriate to BZD abuse.

PMID- 22882335
TI  - Liver-kidney recipients with chronic viral hepatitis C treated with interferon
      alpha.
AB  - Antiviral therapy with interferon-alpha (IFN-alpha) and pegylated IFN-alpha (PEG
      IFN-alpha) for chronic hepatitis C (HCV)-infected kidney recipients remains
      controversial. IFN-alpha is not recommended in most cases because it induces
      severe acute graft rejection. However, IFN-alpha, as PEG-IFN-alpha, is associated
      with a more pronounced immune response, and is well tolerated in HCV-infected
      liver recipients without causing graft rejection. In combined liver-kidney
      transplant (LKT) recipients, IFN-alpha has been occasionally used and appears to
      be well tolerated. All LKT recipients with a functioning kidney and liver having
      a HCV replication and who needed IFN-alpha therapy have been included in the
      study. The occurrence of liver and/or renal acute rejection as well as the HCV
      replication has been collected. A total of 12 LKT patients treated with PEG-IFN
      alpha plus ribavirin have been studied. No acute rejection was observed. Renal
      function remained stable during and after discontinuing treatment, without any
      graft dysfunction. Two patients had a partial viral response and four had a
      sustained viral response. All patients, whatever their viral response, had
      decreased liver-enzyme levels. Response to PEG-IFN-alpha therapy was correlated
      with steroid dose and transaminase level when PEG-IFN-alpha was started. These
      data suggest that the combination therapy of PEG-IFN-alpha plus ribavirin did not
      have a higher risk of acute kidney-graft rejection after liver-kidney
      transplantation.

PMID- 22882336
TI  - First two cases of adult-onset type II citrullinemia successfully treated by
      deceased-donor liver transplantation in Japan.
AB  - We report the first two cases of adult-onset type II citrullinemia (CTLN2)
      successfully treated by liver transplantation from deceased donors in Japan. One
      patient was a 34-year-old female, who had suffered from depression since the age
      of 28 years and developed consciousness disturbance at 34 years old. The other
      patient was a 41-year-old man who began to experience consciousness disturbance
      with abnormal behavior at 37 years old. Both patients were first treated with non
      surgical therapies, including low-carbohydrate diet, arginine granules and sodium
      pyruvate. However, their therapeutic efficacy was limited and attacks of
      encephalopathy occurred frequently with elevation of plasma ammonia despite
      treatment. While both patients and their families desired liver transplantation,
      no candidate donors for live-donor liver transplantation were available.
      Fortunately, within a relatively short period after enrollment for liver
      transplant from deceased donors in Japan (13 and 43 days, respectively), they
      underwent cadaveric liver transplantation. The clinical courses after the
      operation were uneventful in both cases and no attacks of hepatic encephalopathy
      have occurred. Although there have been no reports of good therapies for CTLN2
      patients with resistance to non-surgical therapies and no live-donor candidates,
      our observations indicate that cadaveric liver transplantation can be a promising
      therapeutic option for CTLN2 patients.

PMID- 22882337
TI  - Churg-Strauss syndrome manifesting as cholestasis and diagnosed by liver biopsy.
AB  - A 56-year-old woman was referred to our hospital due to fever and cholestatic
      liver dysfunction. Her eosinophil count was normal and she had no abdominal pain
      or neurological manifestations. We performed a liver biopsy and found fibrinoid
      necrosis of the hepatic artery with granulomatous reaction and eosinophilic
      infiltration in the portal area in the liver. Later, sensory abnormalities of the
      arms and legs appeared and the eosinophil count increased. Serum immunoglobulin E
      and immunoglobulin G4 were elevated and rheumatoid factor was strongly positive.
      Endoscopic retrograde cholangiopancreatography revealed no abnormality of the
      bile duct and pancreatic duct. We made a diagnosis of Churg-Strauss syndrome and
      began corticosteroid treatment. Fever and liver function immediately improved. In
      the present patient, Churg-Strauss syndrome manifested first in the liver, before
      hypereosinophilia and neural manifestations. We believe that Churg-Strauss
      syndrome is an autoimmune liver disease, and it is important to recognize that
      the liver may be involved in Churg-Strauss syndrome.

PMID- 22882338
TI  - Hepatocellular carcinoma in a patient treated with efalizumab for psoriasis.

PMID- 22882339
TI  - Anti-hepatitis B virus therapy: To stop, or not to stop: Has the question been
      solved?

PMID- 22882340
TI  - Instruments for assessing the risk of falls in acute hospitalized patients: a
      systematic review protocol.
AB  - AIM: The purpose of this article is to present the research protocol of a
      systematic review about fall risk assessment tools in acute hospitalized
      patients. BACKGROUND: Various risk assessment tools for falls have been
      developed, but with uncertainties derived from validation in heterogeneous
      environments and variations in their sensitivity, specificity and predictive
      validity. DESIGN: Systematic review and meta-analysis. METHODS: Two independent
      reviewers will extract data in a blinded process. Quality of studies will be
      assessed using various standardized instruments. A meta-analysis will be
      performed if applicable. For all studies, sensitivity, specificity, positive and
      negative predictive values, together with the positive and negative likelihood
      ratios and Youden index will be calculated. The diagnostic odds ratio of the
      studies and the hierarchical summary Relative Operating Characteristic curve and
      bivariate model will be applied. Calculations will be made from random effects
      models. Forest-plot diagrams for sensitivity and specificity and likelihood
      ratios, in addition to Cochrane's Q test and the I(2)  statistic, will be
      calculated. Funding of the review was confirmed in December 2010. DISCUSSION: The
      results of this review will help to clarify some uncertainties provoked by
      earlier research findings and enable informed choice of a validated, reproducible
      instrument for assessing the risk of falls by hospital patients, so that
      preventive action may be taken to minimize this risk.

PMID- 22882341
TI  - Surround modulation in cortical orientation map revealed by optical imaging and
      its dependency on receptive field eccentricity.
AB  - Optical imaging was used to investigate the difference in surround modulation on
      orientation map related to receptive field eccentricity in cat visual cortex.
      Presentation of center-surround stimuli at the center of gaze resulted in no
      clear surround modulation; however, significant modulation was observed in its
      corresponding cortical area when the center-surround stimuli were presented at 10
      degrees  eccentricity in more peripheral parts of the visual field. Modulation
      was observed both in the response magnitude and in the spatial pattern of the
      response. Surround orientation perpendicular to the orientation of a center patch
      grating showed the largest modulation in the response magnitude. The modulation
      became weaker as the orientation difference between the center and surround
      gratings became smaller. Regardless of the orientations for the central patch
      gratings, a similar response spatial pattern was observed in the cortical region
      where the underlying cells had their receptive fields covering the central patch,
      if the stimuli were with the same surround gratings. These properties support the
      notion of a relative specialization for visual information processing in
      peripheral representations of cortical areas.

PMID- 22882342
TI  - From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem
      cell transplantation in a RAG1 deficient family.
AB  - BACKGROUND: Mutations in RAG genes cause a spectrum of severe immunodeficiencies
      ranging from Severe Combined Immunodeficiency (SCID) T-B-NK+ to Omenn syndrome
      (OS) through intermediate phenotypes, even for the same alteration. Nowadays,
      hematopoietic stem cell transplantation (HSCT) is the unique curative treatment
      available. METHODS: We describe three related patients from a Moroccan
      consanguineous family. Patient 1 developed at 1 month of age moderate eczematous
      dermatitis with eosinophilia, followed by infections and enteritis. He was
      transplanted and received reduced intensity conditioning regimen previous to
      HSCT. His brother, patient 2, was born preterm with a severe neonatal
      erythroderma, hepatosplenomegaly and lymphadenopathy. Patient 3, cousin of the
      two siblings, was also born preterm and fulfilled all criteria for classical OS.
      Immunological evaluation was performed and RAG genes were sequenced. RESULTS:
      Immunological data from all three patients were very diversed, from T lymphopenia
      to marked lymphocytosis, and different degrees of eosinophilia and IgE levels.
      Non-responder T cells and absent B cells were constant. All patients presented
      the same homozygous mutation in RAG1 gene (c.631delT). Patient 1 fully recovered
      both clinically and immunologically after HSCT. Two years later, he lost the
      accomplished lymphoid chimera and the disease relapsed as a classical OS, leading
      to patient's death. CONCLUSIONS: This is the first report of a RAG1 deficient
      patient with a changed clinical and immunological phenotype from SCID to OS after
      HSCT. The use of a myeloablative conditioning regimen that eliminates reminiscent
      T cells might have improved patient's outcome and it should be considered in
      similar cases.

PMID- 22882343
TI  - A comparison of near-dissociated heterophoria tests in free space.
AB  - BACKGROUND: Many clinical techniques exist to quantify the magnitude of
      heterophoria in free space. In this article, we determine the agreement between
      the modified Thorington test and three different tests for dissociated
      heterophoria at near distance in free space. METHODS: The modified Thorington,
      Maddox rod, von Graefe and alternate cover tests were performed on 49 university
      students at near distance in free space. The 95% limits of agreement between the
      modified Thorington and other tests were compared in pairs by using the Bland
      Altman statistical test. RESULTS: While the Maddox rod-modified Thorington pair
      showed narrow 95% limit range (2.5 to -3.34(Delta) ) between each other compared
      to the von Graefe-modified Thorington (4.2 to -3.15(Delta) ) and alternate cover
      test-modified Thorington pairs (4.52 to -2.77(Delta) ), none of the three tests
      showed good agreement with the modified Thorington test. CONCLUSION: The modified
      Thorington test cannot be interchanged with the other three near tests for
      heterophoria in free space. The accuracy in the measurement and the different
      methods of dissociation may play a crucial role in comparisons of the different
      tests for heterophoria.

PMID- 22882344
TI  - Single transseptal big Cryoballoon pulmonary vein isolation using an inner lumen
      mapping catheter.
AB  - BACKGROUND: The single big cryoballon technique for pulmonary vein isolation
      (PVI) has been limited by the need for two transseptal punctures (TP). We
      therefore investigated feasibility and safety of a simplified approach using a
      single TP and a novel circumferential mapping catheter (CMC). METHODS: Patients
      underwent 28-mm cryoballoon PVI using a single TP. The CMC (Achieve((c))
      Medtronic Inc., Minneapolis, MN, USA) served as (1) guidewire and (2) as a PV
      mapping tool. Primary endpoint was PVI without switching to a regular guidewire.
      Secondary endpoints included: (1) PV signal quality during freezing, (2) time to
      PVI, (3) classification of successful ablation technique, (4) complications, and
      (5) procedural data. RESULTS: A total of 32 patients (126 PVs) were studied (mean
      age: 62 +/- 11 years, 24 males, left atrium: 40 +/- 4 mm). The primary endpoint
      was achieved in 29/32 patients (91%) and 123/126 PVs (98%) with a procedure and
      fluoroscopy time of 126 +/- 26 minutes and 18.9 +/- 7.5 minutes, respectively.
      Real-time visualization of PVI could be observed in 61/126 (48%) PVs. Time to
      sustained PVI versus nonsustained PVI was 66 +/- 56 seconds versus 129 +/- 76
      seconds (P < 0.001). One phrenic nerve palsy was observed. After a follow-up of
      250 +/- 84 days 23/32 patients (72%) remained in sinus rhythm. CONCLUSION: The
      "simplified single big cryoballoon" PVI strategy appears to be safe and feasible.
      However, real-time PV recording was achieved in <50% of PVs. Therefore, further
      catheter refinements are warranted. (PACE 2012; 35:1304-1311).

PMID- 22882345
TI  - Toxic epidermal necrolysis with failure of re-epithelialization. Could umbilical
      cord mesenchymal stem cell transplantation have a role?

PMID- 22882346
TI  - Commentary.

PMID- 22882347
TI  - Short-term and medium-term clinical outcomes of Campylobacter concisus infection.
AB  - There are only sparse data on the short-term and medium-term clinical impacts of
      Campylobacter concisus infection. A clinical study was performed during a 2-year
      period to determine the clinical manifestations in C. concisus-positive adult
      patients. A case patient was defined as an adult patient (>=18 years) with a C.
      concisus-positive stool sample during the study period. Clinical data were
      obtained with use of a questionnaire supplemented with the patients' medical
      records, if any. The short-term and medium-term clinical manifestations in these
      patients were compared with those of patients with Campylobacter
      jejuni/Campylobacter coli infection. One hundred and seventy-four C. concisus
      patients and 196 C. jejuni/C. coli patients participated in the study. Patients
      with pre-existing inflammatory bowel disease or microscopic colitis or enteric co
      infection were excluded from review of the clinical manifestations. Comparison of
      the short-term clinical manifestations in 139 C. concisus patients with those in
      187 C. jejuni/C. coli patients showed a significantly lower prevalence of fever,
      chills, mucus and blood in stools, and weight loss. However, 80% of C. concisus
      patients, but only 32% of C. jejuni/C. coli patients, had diarrhoea for >2 weeks.
      After a 6-month follow-up period, 12% of C. concisus patients were diagnosed with
      microscopic colitis, whereas no C. jejuni/C. coli patients were diagnosed with
      non-infective colitis. Irritable bowel symptoms were common in both groups at
      follow-up. C. concisus infection seems to cause a milder course of acute
      gastroenteritis than C. jejuni/C. coli infection, but is associated with more
      prolonged diarrhoea.

PMID- 22882348
TI  - Fine-scale genetic population structure in a mobile marine mammal: inshore
      bottlenose dolphins in Moreton Bay, Australia.
AB  - Highly mobile marine species in areas with no obvious geographic barriers are
      expected to show low levels of genetic differentiation. However, small-scale
      variation in habitat may lead to resource polymorphisms and drive local
      differentiation by adaptive divergence. Using nuclear microsatellite genotyping
      at 20 loci, and mitochondrial control region sequencing, we investigated fine
      scale population structuring of inshore bottlenose dolphins (Tursiops aduncus)
      inhabiting a range of habitats in and around Moreton Bay, Australia. Bayesian
      structure analysis identified two genetic clusters within Moreton Bay, with
      evidence of admixture between them (F(ST) = 0.05, P = 0.001). There was only weak
      isolation by distance but one cluster of dolphins was more likely to be found in
      shallow southern areas and the other in the deeper waters of the central northern
      bay. In further analysis removing admixed individuals, southern dolphins appeared
      genetically restricted with lower levels of variation (AR = 3.252, pi = 0.003)
      and high mean relatedness (r = 0.239) between individuals. In contrast, northern
      dolphins were more diverse (AR = 4.850, pi = 0.009) and were mixing with a group
      of dolphins outside the bay (microsatellite-based STRUCTURE analysis), which
      appears to have historically been distinct from the bay dolphins (mtDNA Phi(ST) =
      0.272, P < 0.001). This study demonstrates the ability of genetic techniques to
      expose fine-scale patterns of population structure and explore their origins and
      mechanisms. A complex variety of inter-related factors including local habitat
      variation, differential resource use, social behaviour and learning, and
      anthropogenic disturbances are likely to have played a role in driving fine-scale
      population structure among bottlenose dolphins in Moreton Bay.

PMID- 22882349
TI  - Enhancing motivation to change in eating disorders with an online self-help
      program.
AB  - Ambivalence to change is a major obstacle to treating people with eating
      disorders. Enhancing motivation to change can contribute to recovery from the
      disorders. This study used an Internet-based self-help program developed in the
      Asia-Pacific region to identify the motivational stages of change in people with
      eating disorders. It explored their perceptions of the benefits and costs of
      taking action against their eating disorders, and assessed their involvement in
      motivational enhancement exercises and their improvement in eating disorder
      psychopathology. A total of 185 participants, aged 16-50 years (mean age, 26.5)
      were involved in the open-trial program with a motivational enhancement component
      and completed the Motivational Stages of Change Questionnaire (MSCARED), the
      Eating Disorder Examination Questionnaire version 5 (EDE-Q5) and the Eating
      Disorder Inventory version 3 (EDI-3). The results show that more participants
      perceived the benefits of taking action against their eating disorders than the
      costs. Completer analysis shows that they experienced significant improvement in
      motivational stages of change and eating disorder psychopathology, from a
      baseline assessment to 1-month and 3-month follow ups. The self-help program has
      potential benefit for people with eating disorders and its use could be
      encouraged by health-care professionals to enhance the motivation to change and
      facilitate recovery.

PMID- 22882350
TI  - Time to define an international standard of postoperative care for resected upper
      urinary tract transitional cell carcinoma (TCC) - opening of the peri-operative
      chemotherapy versus surveillance in upper tract urothelial cancer (POUT) Trial.

PMID- 22882351
TI  - Divergence on floral traits and vertebrate pollinators of two endemic Encholirium
      bromeliads.
AB  - Shifts in pollen vectors favour diversification of floral traits, and differences
      in pollination strategies between congeneric sympatric species can contribute to
      reproductive isolation. Divergence in flowering phenology and selfing could also
      reduce interspecific crossing between self-compatible species. We investigated
      floral traits and visitation rates of pollinators of two sympatric Encholirium
      species on rocky outcrops to evaluate whether prior knowledge of floral
      characters could indicate actual pollinators. Data on flowering phenology,
      visitation rates and breeding system were used to evaluate reproductive
      isolation. Flowering phenology overlapped between species, but there were
      differences in floral characters, nectar volume and concentration. Several
      hummingbird species visited flowers of both Encholirium spp., but the endemic bat
      Lonchophylla bokermanni and an unidentified sphingid only visited E. vogelii.
      Pollination treatments demonstrated that E. heloisae and E. vogelii were
      partially self-compatible, with weak pollen limitation to seed set. Herbivores
      feeding on inflorescences decreased reproductive output of both species, but for
      E. vogelii the damage was higher. Our results indicate that actual pollinators
      can be known beforehand through floral traits, in agreement with pollination
      syndromes stating that a set of floral traits can be associated with the
      attraction of specific groups of pollinators. Divergence on floral traits and
      pollinator assemblage indicate that shifts in pollination strategies contribute
      to reproductive isolation between these Encholirium species, not divergence on
      flowering phenology or selfing. We suggest that hummingbird pollination might be
      the ancestral condition in Encholirium and that evolution of bat pollination made
      a substantial contribution to the diversification of this clade.

PMID- 22882352
TI  - Intraoperative cell salvage in a combat support hospital: a prospective proof of
      concept study.
AB  - BACKGROUND: Provision of transfusion support is an important element of
      contemporary military operations, but presents a considerable logistic burden.
      Intraoperative blood salvage (IBS) offers the potential to reduce dependency on
      donated red blood cell (RBC) supply. The aim of this study was to assess the
      feasibility of IBS in an operational environment. STUDY DESIGN AND METHODS: A
      "salvage-only" IBS feasibility study was undertaken in a deployed, Anglo-American
      combat support hospital. All adult patients admitted with combat-related injuries
      likely to require more than 10 units of RBCs in 12 hours were included. The
      volume of salvaged blood available for reinfusion was collated with injury type.
      RESULTS: A total of 130 patients were admitted having sustained combat-related
      injury. Twenty-nine fulfilled the criteria, of which 27 were identified on
      admission. Eighteen cases were selected for IBS and salvage was completed in 17.
      From these 17, the mechanism of injury was 24% gunshot wound (GSW) and 76% blast
      injury, and injury type was 47% body cavity and 53% extremity. A total of 5578g
      RBC mass was salvaged and prepared for reinfusion, representing 7.6% of total
      requirement. The proportion of RBC mass salvaged to that required was greatest in
      those with GSWs and cavity injuries, being 39% (673g/1733g) and 16% (243g/1497g),
      respectively. CONCLUSION: Salvage is most successful in patients with GSWs and
      cavity injuries and less appropriate for limb and blast injuries. However, the
      results of this study present more arguments against IBS than for it, and further
      research is needed to determine its safety in combat settings.

PMID- 22882353
TI  - Treatment of hypovitaminosis D with pharmacologic doses of cholecalciferol, oral
      vs intramuscular; an open labeled RCT.
AB  - OBJECTIVE: Vitamin D deficiency is a worldwide health problem. Usual supplements
      are inadequate for prevention of hypovitaminosis D, and much higher doses are
      needed for its treatment. This study was designed to compare the efficacy and
      practicality of high-dose intramuscular and oral cholecalciferol in treatment of
      hypovitaminosis D and to evaluate durability of the effect of each remedy.
      DESIGN: Ninety-two patients with hypovitaminosis D [serum 25(OH) D level < 75
      nmol/l] were enrolled in a randomised clinical trial. Participants were randomly
      assigned to receive 300 000 IU cholecalciferol, either intramuscularly as a
      single injection or orally in six divided doses during 3 months period. Serum
      25(OH) D level was measured at baseline and at 3 and 6 months. RESULTS: Both
      treatment regimens significantly increased the serum 25(OH)D level. Delta change
      in serum 25(OH) D level from baseline (presented as mean +/- SEM) at month 3 was
      significantly higher in oral than injection group (90 +/- 11.2 and 58.8 +/- 8.9
      nmol/l, respectively, P = 0.03); but was similar at 6th month intervention (52.1
      +/- 7.6 and 62.2 +/- 6.7 nmol/l, respectively, P = 0.32). There was a marginally
      significant trend in favour of oral group in the proportion of cases attained
      vitamin D adequacy at 6th month (P = 0.06); but still 15% of all patients
      remained at < 50 nmol/l. CONCLUSION: Both regimens were considerably effective,
      safe and practical in treating hypovitaminosis D. Although we revealed
      superiority of oral route, at least at early short time, the way of treatment may
      depend on the patient's choice, compliance and availability of various forms of
      the drug in any regions.

PMID- 22882354
TI  - Late-onset focal dermal elastosis: an uncommon mimicker of pseudoxanthoma
      elasticum.
AB  - Late-onset focal dermal elastosis is a rare disorder that presents clinically
      with the development of small white-to-yellow papules simulating pseudoxanthoma
      elasticum (PXE) in otherwise healthy adults in the seventh through ninth decades.
      It is characterized histopathologically by foci of increased normal-appearing
      elastic tissue in the reticular dermis. The disorder lacks any of the systemic
      complications of PXE and clinically resembles several other elastic tissue
      disorders that mimic PXE. We report two cases of late-onset focal dermal
      elastosis. The first is of a 75-year-old female who presented with symmetrically
      distributed, 2-5 mm white-to-yellow, discrete and coalescing, non-follicular
      papules on the posterolateral neck, anterior chest and axillae. The second case
      involves a 39-year-old female who presented with asymptomatic flesh-colored
      lesions on the posterior neck, back, antecubital and popliteal fossae, thighs,
      forearms and wrists. Skin biopsies in each case revealed aggregates of elastic
      fibers in the reticular dermis without calcification. The differential diagnosis
      of clinical and histopathologic imitators of PXE is discussed.

PMID- 22882355
TI  - Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G
      polymorphisms with risk of spontaneously aborted fetuses.
AB  - PROBLEM: The miR-196a2T>C and miR-499A>G polymorphisms have been reported to be
      genetic risk factors for recurrent spontaneous abortion; however, that previous
      study focused on the genetic analyses of pregnant women rather than aborted
      fetuses. Because annexin A1 is a target of miR-196a2 and is related to anti
      inflammation, miR-196a2 may be immunologically important. Moreover, miR-146a, miR
      149, miR-196a2, and miR-499 have shown associations with immune responses. METHOD
      OF STUDY: One hundred and eighty-two spontaneously aborted fetuses (SAFs) were
      <20 weeks of gestational age. The control subjects were 101 healthy children and
      302 adults collected from a convenience sample. Polymerase chain reaction and
      restriction fragment length polymorphism analysis was performed to identify the
      miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G genotypes. RESULTS:
      Chromosomally normal SAFs had significantly different frequencies of the miR
      196a2CC, miR-146aCC/miR-196a2CC, and miR-149TT/miR-196a2CC genotypes compared
      with control subjects. CONCLUSIONS: miR-196a2CC, miR-146aCC/miR-196a2CC, and miR
      149TT/miR-196a2CC in fetuses are possible risk factors for spontaneous abortion.

PMID- 22882356
TI  - Postpartum depression: the (in) experience of Brazilian primary healthcare
      professionals.
AB  - AIM: This article reports experiences of Brazilian physicians and nurses caring
      for women with postpartum depression in primary healthcare settings. BACKGROUND:
      Prevalence of postpartum depression in Brazil ranges from 12-37%, which fits with
      international claims about differences in the magnitude of the problem and
      consistency of screening. DESIGN: Qualitative descriptive. METHOD: This study was
      situated in health units of the Family Health Strategy in Campina Grande, Brazil.
      Data were collected from September 2010-January 2011 through open-ended
      interviews with ten nurses and seven physicians, observations, and field diary
      records. Inductive content analysis was used to develop categories. FINDINGS:
      Three categories: (1) Limited professional exposure to postpartum depression; (2)
      Postpartum depression as the domain of psychiatry; and (3) Challenges dealing
      with postpartum depression demonstrated that few professionals felt postpartum
      depression merited their attention. Women, with signs of postpartum depression,
      were usually identified by family members who noticed behaviours that seemed
      abnormal. Care providers indicated they had inadequate time and access to
      screening techniques to identify women with depression attending unit-based
      pregnancy and postpartum groups. When identified, women were referred directly to
      psychiatric care. CONCLUSION: Without consistent screening and diagnostic
      techniques, Brazilian health professionals are insecure about identifying and
      treating cases of postpartum depression. Referring women to psychiatric units
      entail more time for women to be diagnosed and treated and increased costs for
      health services. Primary healthcare professionals require training to screen,
      identify, and treat postpartum depression in primary healthcare settings.

PMID- 22882357
TI  - Denial of prescription opioids among young adults with histories of opioid
      misuse.
AB  - OBJECTIVES: An exploratory study was undertaken to examine how being denied
      prescription opioids to treat pain impacted the drug-using careers of young
      adults with a history of misuse of prescription drugs. DESIGN: Ethno
      epidemiological methodology utilizing a cross-sectional design, semi-structured
      interviews, and qualitative/quantitative data analysis. Settings.  Non-clinical
      participants were recruited from natural settings, such as streets, parks,
      beaches, and college campuses, in New York City and Los Angeles during 2008 and
      2009. PARTICIPANTS: One hundred fifty participants aged 16 to 25 who had misused
      a prescription opioid, tranquilizer, or stimulant in the past 90 days. Outcome
      Measures.  Analyses focused on denial of opioids and associated consequences,
      including self-medication with prescription opioids and heroin. RESULTS: Thirty
      four participants (22.7%) described being denied prescription opioids for the
      treatment of a painful condition. Current opioid misuse and current pain problems
      were higher in this group compared to those who had never been denied
      prescription opioids. Reasons for denial included being identified as a drug user
      by a physician, lack of health insurance, and having medication withheld by a
      parent or authority figure. Approximately half reported self-medicating pain with
      either illegally obtained prescription opioids or heroin. Self-medication often
      coincided with initiation of new risk behaviors and more intensive drug use.
      CONCLUSION: Being denied prescription opioids was an important moment in the drug
      using careers of many study participants. Results suggest that effective pain
      management techniques are needed to prevent high-risk young adults with pain
      problems from engaging in escalated opioid misuse and risk behaviors.

PMID- 22882358
TI  - Protoporphyrin IX formation and photobleaching in different layers of normal
      human skin: methyl- and hexylaminolevulinate and different light sources.
AB  - Topical photodynamic therapy (PDT) is used for various skin disorders, and
      selective targeting of specific skin structures is desirable. The objective was
      to assess accumulation of PpIX fluorescence and photobleaching within skin layers
      using different photosensitizers and light sources. Normal human skin was tape
      stripped and incubated with 20% methylaminolevulinate (MAL) or 20%
      hexylaminolevulinate (HAL) for 3 h. Fluorescence microscopy quantified PpIX
      accumulation in epidermis, superficial, mid and deep dermis, down to 2 mm. PpIX
      photobleaching by light-emitting diode (LED, 632 nm, 18 and 37 J/cm(2)), intense
      pulsed light (IPL, 500-650 nm, 36 and 72 J/cm(2)) and long-pulsed dye laser
      (LPDL, 595 nm, 7.5 and 15 J/cm(2)) was measured using fluorescence photography
      and microscopy. We found higher PpIX fluorescence intensities in epidermis and
      superficial dermis in HAL-incubated skin than MAL-incubated skin (P < 0.001). In
      mid and deep dermis, fluorescence intensities were higher (37%) in HAL-treated
      skin than MAL-treated skin, although not significant (P = ns). At skin surface,
      photobleaching was significantly higher (90-98%) after LED illumination (18 and
      37 J/cm2) than IPL (29-53%, 36 and 72 J/cm2) and LPDL (43-62%, 7 and 15 J/cm2) (P
      < 0.001). Within the skin, photobleaching was steady from epidermis to deep
      dermis by LED illumination (37 J/cm2, P = ns), but declined from epidermis to mid
      and deep dermis for IPL-treated skin and LPDL-treated skin (IPL 72 J/cm2: 26-15%;
      LPDL 15 J/cm2: 37-23%) (P < 0.04). Clinically, erythema correlated linearly with
      MAL and HAL-induced photobleaching (r2 = 0.175, P < 0.001). In conclusion,
      selective PpIX accumulation indicates HAL as an alternative to MAL for epidermal
      targeted PDT. In clinically relevant doses, PpIX photobleaching throughout the
      skin was more profound following LED than LPDL and IPL exposure.

PMID- 22882359
TI  - Contribution of highly sensitive diagnostic methods to the diagnosis of systemic
      mastocytosis in the absence of skin lesions.

PMID- 22882360
TI  - Effects of low-frequency hippocampal stimulation on gamma-amino butyric acid type
      B receptor expression in pharmacoresistant amygdaloid kindling epileptic rats.
AB  - OBJECTIVE: To observe the effect of low-frequency hippocampal stimulation on
      gamma-amino butyric acid type B (GABA-B) receptor expression in hippocampus
      pharmacoresistant epileptic rats. MATERIALS AND METHODS: Sixteen
      pharmacoresistant epileptic rats were selected by testing their seizure response
      to phenytoin and phenobarbital, and they were randomly divided into a
      pharmacoresistant control group (PRC group, eight rats) and a pharmacoresistant
      stimulation group (PRS group, eight rats). Another 16 pharmacosensitive epileptic
      rats were served as control, also divided randomly into a pharmacosensitive
      control group (PSC group) and a pharmacosensitive stimulation group (PSS group).
      A stimulation electrode was implanted into the rats' hippocampus in the four
      groups. Low-frequency hippocampal stimulation was administered twice per day for
      two weeks. Following these weeks of stimulation, GABA-B receptor-positive neurons
      were counted and the gray values of GABA-B receptor expression in the rats'
      hippocampal tissues were measured. RESULTS: The amygdale stimulus-induced
      epileptic seizures were decreased significantly in the PRS group compared with
      the PRC group. The parameters of the amygdale after discharge also were improved
      after hippocampal stimulation. Simultaneously, the GABA-B receptor-positive
      neurons increased and the GABA-B expression gray values decreased markedly in the
      PRS group compared with the PRC group. The same phenomenon also was observed
      between the PSS group and the PSC group. However, no significant difference was
      found in the GABA-B receptor-positive neurons and the gray values of GABA-B
      between the PRS group and the PSC group. CONCLUSIONS: The low-frequency
      hippocampal stimulation may inhibit the amygdale stimulus-induced epileptic
      seizures and the after discharges. The antiepileptic effects of the hippocampal
      stimulation may be achieved partly by increasing the expression of the GABA-B
      receptor.

PMID- 22882361
TI  - Characterization of thorn-shaped astrocytes in white matter of temporal lobe in
      Alzheimer's disease brains.
AB  - Thorn-shaped astrocytes (TsA) are mainly localized in the periventricular white
      matter of the temporal lobe in a subgroup of aged individuals usually in the
      context of Alzheimer's disease (AD). Immunohistochemistry of TsA shows 4Rtau
      deposition, tau phosphorylation at different sites recognized with
      phosphospecific anti-tau antibodies Thr181, Ser202, Ser214, Thr231, Ser396,
      Ser422, and clones AT8 and PHF-1, and conformational changes revealed with Alz50
      and MC-1 antibodies; TsA are also immunostained with antibodies to active tau
      kinases MAPK/ERK-P, SAPK/JNK-P, p38-P and GSK-3beta. These findings are common to
      neurofibrillary tangles in AD. However, TsA are not stained with 3Rtau
      antibodies, and they are seldom stained or not at all with phosphospecific
      tauSer262 and with Tau-C3 antibody, which recognizes the latter tau truncation at
      aspartic acid 421. Previous studies have shown that tau phosphorylation at Ser262
      reduces tau binding to microtubules and increases caspase-3 activity, whereas tau
      truncation at aspartic acid 421 is associated with tau ubiquitination, and toxic
      effects of tau. In this line, ubiquitin is not accumulated in TsA, and in situ
      end-labeling of nuclear DNA fragmentation shows absence of degeneration in TsA.
      These observations support the concept that tau lesions in neurons differ from
      those seen in TsA in AD.

PMID- 22882362
TI  - Positive impact of Australian 'blindness' tobacco warning labels: findings from
      the ITC four country survey.
AB  - BACKGROUND: Smokers with greater knowledge of the health effects of smoking are
      more likely to quit and remain abstinent. Australia has communicated the causal
      association of smoking and blindness since the late 1990s. In March 2007,
      Australia became the first country to include a pictorial warning label on
      cigarette packages with the message that smoking causes blindness. The current
      study tested the hypothesis that the introduction of this warning label increased
      smokers' knowledge of this important health effect. METHODS: Six waves of the
      International Tobacco Control Four Country Survey were conducted, as a telephone
      survey of 17,472 adult smokers in Australia, Canada, United Kingdom and the
      United States, with three waves before and three waves after the blindness health
      warning was introduced in Australia. The survey measured adult smokers' knowledge
      that smoking causes blindness. RESULTS: Australian smokers were significantly
      more likely to report that smoking causes blindness, compared to Canadian, UK and
      US smokers, where there were neither health campaigns nor health warnings labels
      about blindness. After the introduction of the blindness warning, Australian
      smokers were more likely than before the blindness warning to report that they
      know that smoking causes blindness (62 versus 49 per cent; OR = 1.68, 95% CI:
      1.03, 2.76, p = 0.04). In Australia, smokers aged over 55 years were less likely
      than those aged 18 to 24 to report that smoking causes blindness (OR = 0.43; 95%
      CI: 0.29, 0.62, p < 0.001). CONCLUSION: While more smokers report that smoking
      causes blindness in Australia compared to other countries, which have not had
      national social marketing campaigns, further gains in knowledge were found after
      pictorial warning labels were introduced in Australia. Findings suggest there is
      still a need to educate the public about the causal association of smoking and
      blindness. More education may be needed to redress the knowledge gap in older
      Australian smokers as the incidence of age-related macular degeneration increases
      with age.

PMID- 22882363
TI  - A life-threatening flecainide overdose treated with intravenous fat emulsion.
AB  - Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR,
      QRS, and QTc prolongation on the electrocardiogram and development of life
      threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid
      resuscitation and the administration of magnesium and sodium bicarbonate. We
      report a case of flecainide overdose associated with life-threatening hemodynamic
      compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE
      should be considered as a novel adjunctive therapy in patients with life
      threatening toxicity following flecainide overdose.

PMID- 22882364
TI  - High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver
      transplantation.
AB  - Treatment options of recurrent hepatocellular carcinoma (HCC) after liver
      transplantation are limited and data on systemic compounds for advanced tumor
      stages in transplant recipients are sparse. We retrospectively analyzed the
      toxicity, tolerability, and efficacy of sorafenib in combination with mTOR
      inhibitors (mTORi), or calcineurin inhibitors (CNI) in transplant recipients with
      recurrent HCC. In total, 20 of 92 patients transplanted for HCC within a 10-year
      time period, experienced tumor recurrence. In case of ineligibility for other
      treatment options, patients received sorafenib (n = 13). In addition, CNI were
      stopped and switched to mTORi in nine patients, whereas CNI were continued in
      four patients. Grade 3-4 adverse events were observed in 92% of all patients
      necessitating sorafenib discontinuation in 77%. The most common severe adverse
      events were acute hepatitis, diarrhea, hand-foot - skin reaction and bone marrow
      suppression. In patients receiving sorafenib/mTORi one patient achieved partial
      response, and four achieved stable disease. In this cohort of liver transplant
      recipients side effects prevented full dosing of sorafenib and necessitated
      discontinuation of sorafenib in the majority of patients, yet antitumor efficacy
      seemed promising in combination with mTORi.

PMID- 22882365
TI  - Metformin for the treatment of hidradenitis suppurativa: a little help along the
      way.
AB  - BACKGROUND: Despite recent insights into its aetiology, hidradenitis suppurativa
      (HS) remains an intractable and debilitating condition for its sufferers,
      affecting an estimated 2% of the population. It is characterized by chronic,
      relapsing abscesses, with accompanying fistula formation within the apocrine
      glandbearing skin, such as the axillae, ano-genital areas and breasts. Standard
      treatments remain ineffectual and the disease often runs a chronic relapsing
      course associated with significant psychosocial trauma for its sufferers.
      OBJECTIVE: To evaluate the clinical efficacy of Metformin in treating cases of HS
      which have not responded to standard therapies. METHODS: Twenty-five patients
      were treated with Metformin over a period of 24 weeks. Clinical severity of the
      disease was assessed at time 0, then after 12 weeks and finally after 24 weeks.
      Results were evaluated using Sartorius and DLQI scores. RESULTS: Eighteen
      patients clinically improved with a significant average reduction in their
      Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to
      0.4. Dermatology life quality index (DLQI) also showed a significant improvement
      in 16 cases, with a drop in DLQI score of 7.6. CONCLUSION: Metformin helps
      control HS with minimal side effects and good patient compliance and can
      represent a further agent in the spectrum of treatments available in the
      treatment of this disease.

PMID- 22882366
TI  - Measured and modelled leaf and stand-scale productivity across a soil moisture
      gradient and a severe drought.
AB  - Environmental controls on carbon dynamics operate at a range of interacting
      scales from the leaf to landscape. The key questions of this study addressed the
      influence of water and nitrogen (N) availability on Pinus palustris (Mill.)
      physiology and primary productivity across leaf and canopy scales, linking the
      soil-plant-atmosphere (SPA) model to leaf and stand-scale flux and leaf
      trait/canopy data. We present previously unreported ecophysiological parameters
      (e.g. V(cmax) and J(max)) for P. palustris and the first modelled estimates of
      its annual gross primary productivity (GPP) across xeric and mesic sites and
      under extreme drought. Annual mesic site P. palustris GPP was ~23% greater than
      at the xeric site. However, at the leaf level, xeric trees had higher net
      photosynthetic rates, and water and light use efficiency. At the canopy scale,
      GPP was limited by light interception (canopy level), but co-limited by nitrogen
      and water at the leaf level. Contrary to expectations, the impacts of an intense
      growing season drought were greater at the mesic site. Modelling indicated a 10%
      greater decrease in mesic GPP compared with the xeric site. Xeric P. palustris
      trees exhibited drought-tolerant behaviour that contrasted with mesic trees'
      drought-avoidance behaviour.

PMID- 22882368
TI  - Twelve-month-olds' comprehension and production of pointing.
AB  - This study explored whether infants aged 12 months already recognize the
      communicative function of pointing gestures. Infants participated in a task
      requiring them to comprehend an adult's informative pointing gesture to the
      location of a hidden toy. They mostly succeeded in this task, which required them
      to infer that the adult was attempting to direct their attention to a location
      for a reason - because she wanted them to know that a toy was hidden there. Many
      of the infants also reversed roles and produced appropriate pointing gestures for
      the adult in this same game, and indeed there was a correlation such that
      comprehenders were for the most part producers. These findings indicate that by
      12 months of age infants are beginning to show a bidirectional understanding of
      communicative pointing.

PMID- 22882369
TI  - How should we question young children's understanding of aspectuality?
AB  - In two experiments, we investigated whether 4- to 5-year-old children's ability
      to demonstrate their understanding of aspectuality was influenced by how the test
      question was phrased. In Experiment 1, 60 children chose whether to look or feel
      to gain information about a hidden object (identifiable by sight or touch). Test
      questions referred either to the perceptual aspect of the hidden object (e.g.,
      whether it was red or blue), the modality dimension (e.g., what colour it was),
      or the object's identity (e.g., which one it was). Children who heard the
      identity question performed worse than those who heard the aspect or dimension
      question. Further investigation in Experiment 2 (N= 23) established that
      children's difficulty with the identity question was not due to a problem
      recalling the objects. We discuss how the results of these methodological
      investigations impact on researchers' assessment of the development of
      aspectuality understanding.

PMID- 22882367
TI  - Current and emerging antiviral treatments for hepatitis C infection.
AB  - Newly licensed direct acting antivirals for hepatitis C virus HCV are able to
      cure up to 75% of patients chronically infected with genotype-1 infection, which
      is the predominant HCV strain in Europe and North America. Emerging antiviral
      therapies promise further increases in virological response, as well as improved
      tolerability, reduced duration of therapy, and will potentially eliminate the
      need for interferon use. This review highlights the main therapeutic agents used
      in current standard of care, including telaprevir and boceprevir. It goes on to
      evaluate the mechanisms of emerging drugs, their stage of development and
      response rates seen in research to date. Finally, it projects into the not too
      distant future to consider treatment strategies involving combinations of agents
      and interferon-free therapies, and in which patients they might prove most
      successful.

PMID- 22882370
TI  - Judging judges: How do children weigh the importance of capability and
      objectivity for being a good decision maker?
AB  - Two studies examined developmental differences in how children weigh capability
      and objectivity when evaluating potential judges. In Study 1, 84 6- to 12-year
      olds and adults were told stories about pairs of judges that varied in capability
      (i.e., perceptual capacity) and objectivity (i.e., the relationship to a
      contestant) and were asked to predict which judge would be more accurate.
      Participants generally preferred capable over incapable judges. Additionally, 10-
      and 12-year-olds adjusted their preferences for the most capable judge based on
      objectivity information. Seventy 6- and 8-year-olds participated in Study 2,
      which was similar to Study 1 except that the judges could both seem incapable
      unless children understood how different decisions require different kinds of
      perceptual capabilities. While 8-year-olds chose judges based on the relevance of
      the perceptual capability, 6-year-olds struggled, seeming to be distracted by the
      valence of the judges' relationships to the contestants. Overall, these results
      support that there are important shifts in how children evaluate decision makers
      from early to middle childhood.

PMID- 22882371
TI  - Children's emotion regulation across and within nations: a comparison of
      Ghanaian, Kenyan, and American youth.
AB  - This research examined national, regional, developmental, and gender differences
      in children's reported management of anger and sadness. Participants (8-15 years)
      were 103 Ghanaian children from a village setting, 142 Ghanaian children from a
      middle-class urban context, 106 Kenyan children from an impoverished urban
      context, and 170 children from the United States in lower to middle-class urban
      areas (58.8% Caucasian). Children completed the Children's Anger and Sadness
      Management Scales (Zeman, Shipman, & Penza-Clyve, 2001) to assess emotion
      management (i.e., effortful control, over control, under control). Comparisons
      across nations indicated that Ghanaian youth reported more overt anger expression
      than youth from Kenya and the United States and less anger inhibition than Kenyan
      youth. U.S. children reported less overt expression and more constraint over
      sadness than Kenyan and Ghanaian children, although Kenyans reported being calmer
      when experiencing sadness than Ghanaian and American youth. Comparing Ghanaian
      regional contexts, village children reported more anger control than urban
      children. Regardless of nationality, boys reported more control over sadness than
      girls who reported more under control of sadness and more over control of anger
      than boys. Future research is needed to build on these descriptive, preliminary
      findings examining under-studied cross-national contexts.

PMID- 22882372
TI  - Effects of morphological Family Size for young readers.
AB  - Dutch children, from the second and fourth grade of primary school, were each
      given a visual lexical decision test on 210 Dutch monomorphemic words. After
      removing words not recognized by a majority of the younger group, (lexical)
      decisions were analysed by mixed-model regression methods to see whether
      morphological Family Size influenced decision times over and above several other
      covariates. The effect of morphological Family Size on decision time was mixed:
      larger families led to significantly faster decision times for the second graders
      but not for the fourth graders. Since facilitative effects on decision times had
      been found for adults, we offer a developmental account to explain the absence of
      an effect of Family Size on decision times for fourth graders.

PMID- 22882373
TI  - Attenuation of change blindness in children with autism spectrum disorders.
AB  - Change blindness refers to the difficulty most people find in detecting a
      difference between two pictures when these are presented successively, with a
      brief interruption between. Attention at the site of the change is required for
      detection. A number of studies have investigated change blindness in adults and
      children with autism spectrum disorders (ASD). Some have produced evidence that
      people with ASD find changes to social stimuli harder to detect and changes to
      non-social stimuli easier to detect, relative to comparison participants.
      However, other studies have produced entirely contradictory findings. There is a
      need for consistency in methodology to aid understanding of change blindness and
      attentional processes in ASD. Here, we replicate a change blindness study
      previously carried out with typically developing (TD) children and adults and
      with adults with ASD. Results reveal attenuated change blindness for non-social
      stimuli in children with ASD relative to TD norms. Our results are interpreted,
      alongside others' findings, as potentially indicative of a complex relationship
      between different influences on attention over time.

PMID- 22882374
TI  - Young children's responses to media representations of intergroup threat and
      ethnicity.
AB  - Two studies are reported in which ethnic majority children's reactions to media
      representations of ethnic minorities are examined. In Study 1, 20 white Scottish
      6-year-olds viewed short television stories in which white or ethnic minority
      children were depicted as hostile to the participants' in-group (threat present)
      or not (threat absent). A strong effect of threat on liking was obtained but no
      effect of ethnicity of target and no interaction. In Study 2, 4- and 6-year-old
      white Scottish children viewed PowerPoint displays in which Scottish people were
      shown only as white (traditional version) or as ethnically diverse (multicultural
      version). Intergroup threat was manipulated. Again, a strong effect of threat was
      obtained. However, when threat was absent, participants exposed to the
      traditional condition liked the white out-group more than the multi-ethnic out
      group, while participants exposed to the multicultural condition liked the multi
      ethnic out-group more than the white out-group. The results are interpreted as
      consistent with the predictions of Social Identity Development Theory.

PMID- 22882376
TI  - Novel biological strategies in the management of anal fistula.
AB  - BACKGROUND: The mostly widely studied biomaterials for the sphincter sparing
      treatment of anal fistulas are fibrin glue and the anal fistula plug (AFP).
      However their overall mean clinical success is only 50-60%. As the understanding
      of the pathology of anal fistula, wound healing and the host response to
      materials has improved, so new biological sphincter-sparing strategies have been
      developed. The aim of this review is to assess the safety and efficacy of these
      novel techniques. METHOD: PubMed, the Cochrane database and EMBASE were
      independently searched. All studies that investigated the potential of a
      biomaterial (defined as any synthetic or biologically derived substance in
      contact with host tissue) to augment the healing of anal fistula without
      sphincter division were included. Studies solely describing the role of fibrin
      glue or an AFP were excluded. Data extraction included type of material, fistula
      aetiology, treatment of the primary tract, fistula healing, incontinence,
      duration of follow-up and any specific complications. Systematic quality
      assessment of the included articles was performed. RESULTS: Twenty-three articles
      were finally selected for review. These included a variety of biological and
      synthetic systems that were employed to deliver selected components of the
      extracellular matrix, growth factors, cytokines, stem cells or drugs to the
      fistula tract. CONCLUSION: To date no study matches fistulotomy with regard to
      long-term fistula eradication rate. This is probably due to implant extrusion,
      inadequate track preparation or an unsuitable material. Future techniques need to
      address all these issues to ensure success. Success should be validated by MRI or
      long-term follow-up.

PMID- 22882375
TI  - Overexpression of corticotropin-releasing factor in Barrington's nucleus neurons
      by adeno-associated viral transduction: effects on bladder function and behavior.
AB  - The stress-related neuropeptide, corticotropin-releasing factor (CRF), is
      prominent in neurons of the pontine micturition center, Barrington's nucleus.
      These neurons co-innervate spinal preganglionic neurons that control the bladder,
      and locus coeruleus (LC) neurons that provide norepinephrine innervation
      throughout the brain. Adeno-associated viral (AAV) vector-mediated transfer of
      CRF cDNA was used to increase CRF expression in Barrington's nucleus neurons and
      investigate the impact of a gain of function in Barrington's nucleus spinal and
      LC projections. AAV transfer of the reverse CRF cDNA sequence served as the
      control. Bladder urodynamics and behavior were assessed 4 weeks after vector
      injection into Barrington's nucleus. Rats with bilateral injections of AAV-CRF
      cDNA into Barrington's nucleus had immunohistochemical evidence of CRF
      overexpression in neurons and transport to the spinal cord and LC. The bladder :
      body weight ratio was greater and micturition pressure was less in these rats
      compared with controls, consistent with an inhibitory influence on bladder
      function. Other indices of urodynamic function were not altered. CRF innervation
      of the LC was increased in rats with bilateral Barrington's nucleus injections of
      AAV-CRF cDNA, and this was associated with increased burying behavior, an
      endpoint of LC activation by CRF. The results provide immunohistochemical
      evidence for viral vector-induced CRF overexpression in Barrington's nucleus
      neurons and underscore the ability of AAV vector-mediated transfer to increase
      CRF function in selective circuits. The findings support an inhibitory influence
      of CRF in Barrington's nucleus regulation of the bladder and an excitatory
      influence on the brain norepinephrine system that translates to behavioral
      activation.

PMID- 22882377
TI  - B cell and T cell immunity in the female genital tract: potential of distinct
      mucosal routes of vaccination and role of tissue-associated dendritic cells and
      natural killer cells.
AB  - The female genital mucosa constitutes the major port of entry of sexually
      transmitted infections. Most genital microbial pathogens represent an enormous
      challenge for developing vaccines that can induce genital immunity that will
      prevent their transmission. It is now established that long-lasting protective
      immunity at mucosal surfaces has to involve local B-cell and T-cell effectors as
      well as local memory cells. Mucosal immunization constitutes an attractive way to
      generate systemic and genital B-cell and T-cell immune responses that can control
      early infection by sexually transmitted pathogens. Nevertheless, no mucosal
      vaccines against sexually transmitted infections are approved for human use. The
      mucosa-associated immune system is highly compartmentalized and the selection of
      any particular route or combinations of routes of immunization is critical when
      defining vaccine strategies against genital infections. Furthermore, mucosal
      surfaces are complex immunocompetent tissues that comprise antigen-presenting
      cells and also innate immune effectors and non-immune cells that can act as
      'natural adjuvants' or negative immune modulators. The functions of these cells
      have to be taken into account when designing tissue-specific antigen-delivery
      systems and adjuvants. Here, we will discuss data that compare different mucosal
      routes of immunization to generate B-cell and T-cell responses in the genital
      tract, with a special emphasis on the newly described sublingual route of
      immunization. We will also summarize data on the understanding of the effector
      and induction mechanisms of genital immunity that may influence the development
      of vaccine strategies against genital infections.

PMID- 22882378
TI  - Is there a direct antimicrobial effect of botulinum neurotoxin type A?
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Several studies describe a reduction of
      symptomatic urinary tract infections in patients with neurogenic detrusor
      overactivity after intradetrusor injections of botulinum neurotoxin A (BoNT/A).
      It was, however, unclear if a direct antibacterial effect of BoNT/A plays a role
      in this clinical observation. This is the first study to investigate a potential
      antibacterial effect of two frequently used BoNT/A formulations (i.e. Botox(r)
      and Dysport(r)), providing evidence that BoNT/A does not exert an antibacterial
      effect on lower urinary tract pathogens. OBJECTIVE: * To determine a potential
      direct antimicrobial effect of botulinum neurotoxin type A (BoNT/A). MATERIALS
      AND METHODS: * A prospective study was carried out using onabotulinumtoxin A
      (Botox(r)) and abobotulinumtoxin A (Dypsort(r)) in agar diffusion and broth
      microdilution assays with various clinical urinary tract isolates (Escherichia
      coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa,
      Acinetobacter baumannii, Citrobacter freundii, Klebsiella oxytoca and Bacillus
      subtilis). * Inhibition zones (mm) of bacteria around a disc containing 20 uL
      saline with 4 IU of Botox(r) were measured in the agar diffusion assay. * Minimal
      inhibitory concentrations (MICs, IU/mL) of both toxins for all bacteria were
      determined in the broth microdilution assay after overnight incubation at 35 
      degrees C. RESULTS: * There was no inhibition zone in the agar diffusion assays
      with any bacterial strain. * The microdilution test using Botox(r) and Dysport(r)
      showed bacterial growth in all dilutions, i.e. MICs > 20 and >100 IU/mL for
      Botox(r) and Dysport(r), respectively. CONCLUSIONS: * BoNT/A has no direct
      antimicrobial effect. * The reduced frequency of symptomatic urinary tract
      infections (sUTIs) in patients with neurogenic detrusor overactivity (NDO) after
      BoNT/A intradetrusor injections seems to be caused by different indirect
      mechanisms, which are still not completely understood.

PMID- 22882379
TI  - Cannibalism can drive the evolution of behavioural phase polyphenism in locusts.
AB  - During outbreaks, locust swarms can contain millions of insects travelling
      thousands of kilometers while devastating vegetation and crops. Such large-scale
      spatial organization is preceded locally by a dramatic density-dependent
      phenotypic transition in multiple traits. Behaviourally, low-density
      'solitarious' individuals avoid contact with one another; above a critical local
      density, they undergo a rapid behavioural transition to the 'gregarious phase'
      whereby they exhibit mutual attraction. Although proximate causes of this phase
      polyphenism have been widely studied, the ultimate driving factors remain
      unclear. Using an individual-based evolutionary model, we reveal that
      cannibalism, a striking feature of locust ecology, could lead to the evolution of
      density-dependent behavioural phase-change in juvenile locusts. We show that this
      behavioural strategy minimizes risk associated with cannibalistic interactions
      and may account for the empirically observed persistence of locust groups during
      outbreaks. Our results provide a parsimonious explanation for the evolution of
      behavioural plasticity in locusts.

PMID- 22882380
TI  - Behavioral feeding problems and parenting stress in eosinophilic gastrointestinal
      disorders in children.
AB  - BACKGROUND: Children with eosinophilic gastrointestinal disorders (EGID) and
      their families are asked to adhere to dietary restrictions which can present
      significant daily challenges. However, little is known about child and family
      functioning and adaptation and the impact of psychosocial functioning (e.g.,
      behavioral feeding problems) on adherence to dietary restrictions in this
      pediatric population. METHODS: We conducted a gender- and age-matched case
      control study wherein parents of children with EGID and healthy control children
      completed measures of behavioral feeding problems, parenting stress, and
      adherence to prescribed dietary restrictions. RESULTS: Children with EGID (n =
      92) have significantly higher levels of behavioral feeding problems than healthy
      controls (n = 89; t = 5.7, p < 0.001; t = 7.9, p < 0.001). In particular, younger
      children demonstrated higher levels of behavioral feeding problems than older
      children. While behavioral feeding problems were not predictive of adherence to
      dietary restriction recommendations, they were positively associated with
      parenting stress. CONCLUSIONS: The study results indicate that, for families
      caring for a child with EGID, higher levels of behavioral feeding problems are
      associated with parent maladjustment or dysfunction. A multidisciplinary
      treatment team is needed to provide comprehensive psychosocial and feeding
      evaluations and treatment in EGID families.

PMID- 22882381
TI  - Reduction of allogeneic red blood cell usage during cardiac surgery by an
      integrated intra- and postoperative blood salvage strategy: results of a
      randomized comparison.
AB  - BACKGROUND: The amount of allogeneic blood transfusion may relate to worse
      outcome in cardiac surgery. The reinfusion of red blood cells (RBCs) lost by
      patients, including those of chest drains, is a promising strategy to minimize
      allogeneic transfusions. STUDY DESIGN AND METHODS: To verify this hypotheis, 1047
      cardiac surgery patients were randomly assigned to either traditional
      intraoperative blood salvage followed by chest drain insertion or intra- and
      postoperative strategy with the Haemonetics cardioPAT system. Allogeneic RBC
      transfusion rate (primary endpoint) and postoperative complications (secondary
      endpoint) were recorded at the time of discharge from the hospital and at first
      month follow-up visit, respectively. RESULTS: The cardioPAT arm received 1.20
      units of allogeneic RBCs per patient, whereas the control group required 2.11
      units per patient, and this difference proved to be highly significant (p=0.02).
      We observed a comparable 45-day mortality rate but a lower rate of deep vein
      thrombosis (p=0.04) and atrial fibrillation (p=0.04) in the cardioPAT arm.
      DISCUSSION: A significant reduction in patient exposure to allogeneic RBCs was
      observed in the cardioPAT system arm. Complications were slightly less frequent
      in the cardioPAT group. The use of the cardioPAT is a safe and effective strategy
      to reduce allogeneic RBC transfusions in cardiac surgery.

PMID- 22882382
TI  - Increased glutathione and mitogen-activated protein kinase phosphorylation are
      involved in the induction of doxorubicin resistance in hepatocellular carcinoma
      cells.
AB  - AIM:   The human hepatocellular carcinoma (HCC) cell line HepG2 can easily
      acquire resistance to doxorubicin. However, the mechanism of action is unclear.
      METHODS:   In the present study, we used confocal microscopy, flow cytometry and
      other methods to reveal the mechanisms by which HepG2 cells acquire doxorubicin
      resistance. RESULTS:   Our results showed that R-HepG2 cells, a doxorubicin
      resistant sub-line of HepG2, exhibited decreased intracellular accumulation of
      doxorubicin and increased expression of P-glycoprotein (P-gp) and multidrug
      resistance-associated protein 1 when compared with HepG2 cells. R-HepG2 cells
      also harbored higher levels of glutathione and increased expression of
      glutathione peroxidase. Furthermore, we demonstrated that the phosphorylation of
      mitogen-activated protein kinases (p38 and c-jun-N-terminal kinases), IkBalpha
      and CREB were increased in R-HepG2 cells. Specific p38 inhibitor SB203580
      decreased P-gp expression. The multi-kinase inhibitor sorafenib tosylate also
      significantly suppressed the phosphorylation of these proteins and inhibited the
      expression of P-gp. CONCLUSION:   These findings reveal that the drug resistance
      could be acquired through mitogen-activated protein kinase-dependent upregulation
      of P-gp. This mechanism protects R-HepG2 cells from the anticancer action of
      doxorubicin.

PMID- 22882383
TI  - Patterns of fungal communities among and within decaying logs, revealed by 454
      sequencing.
AB  - Owing to previous methodological limitations, knowledge about the fine-scale
      distribution of fungal mycelia in decaying logs is limited. We investigated
      fungal communities in decaying Norway spruce logs at various spatial scales at
      two environmentally different locations in Sweden. On the basis of 454
      pyrosequencing of the ITS2 region of rDNA, 1914 operational taxonomic units
      (OTUs) were detected in 353 samples. The communities differed significantly among
      logs, but the physical distance between logs was not found to have a significant
      effect on whether fungal communities had any resemblance to each other. Within a
      log, samples that were closer together generally had communities that showed more
      resemblance to each other than those that were further apart. OTUs characteristic
      for particular positions on the logs could be identified. In general, these OTUs
      did not overlap with the most abundant OTUs, and their ecological role was often
      unknown. Only a few OTUs were detected in the majority of logs, whereas numerous
      OTUs were rare and present in only one or a few logs. Wood-decaying
      Basidiomycetes were often represented by higher sequence reads in individual logs
      than Ascomycete OTUs, suggesting that Basidiomycete mycelia spread out more
      rapidly when established. OTU richness tended to increase with the decay stage of
      the sample; however, the known wood decayers were most abundant in less
      decomposed samples. The fungi identified in the logs represented different
      ecological strategies. Our findings differ from previously published sporocarp
      studies, indicating that the highly abundant fruiting species may respond to
      environment in different ways than the rest of the fungal community.

PMID- 22882384
TI  - Effects of elevated CO2 concentration and water deficit on fructan metabolism in
      Viguiera discolor Baker.
AB  - Elevated [CO2 ] is suggested to mitigate the negative effects of water stress in
      plants; however responses vary among species. Fructans are recognised as
      protective compounds against drought and other stresses, as well as having a role
      as reserve carbohydrates. We analysed the combined effects of elevated [CO2 ] and
      water deficit on fructan metabolism in the Cerrado species Viguiera discolor
      Baker. Plants were cultivated for 18 days in open-top chambers (OTC) under
      ambient (~380 ppm), and high (~760 ppm) [CO2 ]. In each OTC, plants were
      submitted to three treatments: (i) daily watering (control), (ii) withholding
      water (WS) for 18 days and (iii) re-watering (RW) on day 11. Analyses were
      performed at time 0 and days 5, 8, 11, 15 and 18. High [CO2 ] increased
      photosynthesis in control plants and increased water use efficiency in WS plants.
      The decline in soil water content was more distinct in WS 760 (WS under 760 ppm),
      although the leaf and tuberous root water status was similar to WS 380 plants (WS
      under 380 ppm). Regarding fructan active enzymes, 1-SST activity decreased in WS
      plants in both CO2 concentrations, a result consistent with the decline in
      photosynthesis and, consequently, in substrate availability. Under WS and both
      [CO2 ] treatments, 1-FFT and 1-FEH seemed to act in combination to generate
      osmotically active compounds and thus overcome water deficit. The proportion of
      hexoses to sucrose, 1-kestose and nystose (SKN) was higher in WS plants. In WS
      760, this increase was higher than in WS 380, and was not accompanied by
      decreases in SKN at the beginning of the treatment, as observed in WS 380 plants.
      These results suggest that the higher [CO2 ] in the atmosphere contributed to
      maintain, for a longer period, the pool of hexoses and of low DP fructans,
      favouring the maintenance of the water status and plant survival under drought.

PMID- 22882385
TI  - Brain tissue volumes in familial longevity: the Leiden Longevity Study.
AB  - Atrophy is one of the major age-related changes in the brain. The absence of
      brain atrophy in elderly individuals reflects deceleration in the process of
      biological aging. Moreover, results from human twin studies suggest a large
      genetic influence on the variance of human brain tissue volumes. To investigate
      the association of brain volumes with exceptional longevity, we tested whether
      middle-aged to elderly offspring of nonagenarian siblings have larger brain
      volumes than their spouses using magnetic resonance imaging. No differences in
      whole brain, gray matter and white matter volume were found. These brain volumes
      were associated with chronological age in offspring and control subjects (all P <
      0.001). Left amygdalar volume of the offspring was larger (P = 0.03) compared
      with control subjects [mean volume offspring (cm3) (95% confidence interval, CI)
      = 1.39 (1.36-1.42), mean volume control subjects (cm3) (95% CI) = 1.32 (1.29
      1.35)]. Association of left amygdalar volume with familial longevity was
      particularly pronounced when offspring with the oldest long-lived parent were
      compared with control subjects (P = 0.01). Amygdalar volumes were not associated
      with chronological age in both groups. Our findings suggest that the observed
      association of a larger left amygdalar volume with familial longevity is not
      caused by a relative preservation of the left amygdala during the course of aging
      but most likely a result of early development caused by a genetic familial trait.

PMID- 22882386
TI  - Follicular mucinosis and mycosis-fungoides-like drug eruption due to leuprolide
      acetate: a case report and review.
AB  - Leuprolide acetate represents a gonadotropin-releasing hormone agonist, used as
      part of the treatment of prostate cancer. We report an unusual case of
      disseminated urticarial rash following leuprolide injection in a 67-year-old man
      that histopathologically and immunohistochemically resembled mycosis-fungoides,
      including the presence of follicular mucinosis and eosinophils in the follicles.
      This histopathologic pattern has not been previously described as a drug reaction
      pattern due to leuprolide, and it underscores the importance of correlation with
      the clinical impression to arrive at a correct diagnosis.

PMID- 22882389
TI  - Course and treatment of buprenorphine/naloxone withdrawal: an analysis of case
      reports.
AB  - Currently published information on buprenorphine-naloxone withdrawal recommends a
      gradually decreasing dosage over weeks to months. In this case report, abrupt
      cessation of buprenorphine/naloxone at various doses, and after variable
      durations of treatment, resulted in mild opiate withdrawal lasting over
      approximately 1-2 days that did not require additional opioid medication or only
      specific symptom-relieving, non-opioid, medications. Lengthy withdrawal regimens
      might prolong withdrawal symptoms unnecessarily, perhaps increasing the risk of
      re-addiction. Controlled studies of buprenorphine/naloxone withdrawal regimens
      over varying time frames would help to illuminate the most effective means of
      opioid discontinuation and inform clinical care.

PMID- 22882390
TI  - GABRA2 genotype, impulsivity, and body mass.
AB  - BACKGROUND: The goal of this study was to test a hypothesis associating
      impulsivity with an elevated body mass index (BMI). METHODS: To this end, we
      examined associations of BMI with putative genetic, neurophysiological,
      psychiatric, and psychological indicators of impulsivity in 78 women and 74 men
      formerly dependent on alcohol or drugs. A second analysis was designed to test
      the replicability of the genetic findings in an independent sample of 109 women
      and 111 men with a similar history of substance dependence. RESULTS: The results
      of the first analysis showed that BMI was positively correlated with Total and
      Nonplanning Scale Scores on the Barratt Impulsiveness Scale and the number of
      childhood symptoms of Attention-Deficit/Hyperactivity Disorder in women. It was
      also positively correlated, in women, with a GABRA2 variant previously implicated
      as a risk factor for substance dependence and an objective
      electroencephalographic feature previously associated with GABRA2 and relapse
      risk. The second analysis confirmed that the correlation between BMI and the
      substance-dependence-associated GABRA2 genotype was reliable and sex-specific.
      CONCLUSIONS: We conclude that an elevated BMI is associated with genetic,
      neurophysiological, psychiatric, and psychological indicators of impulsivity. The
      sex difference may be explained by greater opportunities to eat and overeat, a
      preference for higher calorie foods, a longer duration of alcohol/drug
      abstinence, or previous pregnancies in women.

PMID- 22882391
TI  - Genetic association of GABA-A receptor alpha-2 and mu opioid receptor with
      cocaine cue-reactivity: evidence for inhibitory synaptic neurotransmission
      involvement in cocaine dependence.
AB  - BACKGROUND: This pilot feasibility study examined the role of genetics in
      laboratory-induced cocaine craving. METHODS: Thirty-four African American,
      cocaine-depend- ent male subjects underwent a baseline assessment, cue-exposure
      session, and genetic analysis. Subjects were classified as either cue-reactive or
      nonreactive. RESULTS: Among single nucleotide polymorphism markers in 13
      candidate genes examined for association with cocaine cue-reactivity, two were
      statistically significant: GABRA2 (coding for GABA-A receptor alpha-2 subunit;
      rs11503014, nominal p= .001) and OPRM1 (coding for mu opioid receptor; rs2236256,
      nominal p= .03). CONCLUSIONS: These pilot results suggest that cocaine craving
      shows variability among cocaine-dependent subjects, and that GABRA2 and OPRM1
      polymorphisms have differential influences on cocaine cue-reactivity, warranting
      studies in future research.

PMID- 22882392
TI  - Mental disorders and cigarette use among adults in the United States.
AB  - BACKGROUND: The goal of this study was to determine the association between
      mental disorders and cigarette consumption and nicotine dependence. METHODS: Data
      were drawn from the National Epidemiologic Survey of Alcohol and Related
      Conditions (NESARC), a nationally representative survey of adults (N = 43,093)
      aged 18 and older. Relationships between specific anxiety disorders, mood
      disorders, nondependent cigarette use, nicotine dependence among the whole
      sample, and nicotine dependence among cigarette users were examined. RESULTS:
      After adjusting for demographics and comorbid mental disorders, generalized
      anxiety disorder (OR = 1.16 (1.29-1.51)), specific phobia (OR = 1.35 (1.21
      1.51)), panic disorder (PD) (OR = 1.90 (1.62-2.23)), major depression (MDD) (OR =
      1.31 (1.16-1.48)), and bipolar disorder (OR = 1.30 (1.09-1.54)) were associated
      with increased likelihood of nondependent cigarette use. Specific phobia (OR =
      1.69 (1.49-1.91)), PD (OR = 1.82 (1.50-2.21)), MDD (OR = 1.59 (1.38-1.84)), and
      bipolar disorder (OR = 1.71 (1.39-2.09)) were associated with increased odds of
      nicotine dependence among the whole sample; social phobia (OR = 1.69 (1.19
      2.40)), specific phobia (OR = 1.69 (1.43-2.01)), MDD (OR = 1.65 (1.34-2.02)), and
      bipolar disorder (OR = 2.38 (1.74-3.24)) were associated with increased risk of
      nicotine dependence among cigarette users. CONCLUSIONS: Specific anxiety
      disorders and mood disorders were uniquely associated with nondependent cigarette
      use, nicotine dependence among the whole sample, and the risk of nicotine
      dependence among cigarette users in the United States. Findings suggest that
      demographic differences, comorbid mood, anxiety, substance, and personality
      disorders all contributed to previously observed associations between mental
      disorders and nicotine dependence, explaining these links in some but not all
      cases.

PMID- 22882393
TI  - The role of ethnic pride and parental disapproval of smoking on smoking behaviors
      among minority and white adolescents in a suburban high school.
AB  - BACKGROUND: Adolescence is a critical developmental period when tobacco use is
      initiated and progression to regular smoking occurs. Another growing concern is
      the mounting evidence of ethnic/racial disparities in the smoking rates and
      adverse health consequences related to smoking. To reduce ethnic/racial
      disparities in smoking behaviors, understanding the protective influences against
      smoking behaviors among minority adolescents is important. Therefore, we examined
      the role of ethnic pride and parental disapproval of smoking on a wide range of
      smoking behaviors in ethnic/racial minority and White adolescents attending a
      suburban high school in Connecticut. METHODS: A total of 870 adolescents
      (ethnic/racial minority: n= 202) completed questions on susceptibility to
      smoking, ever trying a cigarette, smoking at least one cigarette daily in the
      past 30 days, as well as parental disapproval of smoking and ethnic pride in a
      school-wide survey. RESULTS: Logistic regression analyses indicated that
      perceived parental disapproval of adolescent smoking and ethnic pride were
      associated with susceptibility to smoking, ever trying a cigarette, and daily
      smoking differently for minority and White adolescents. For White youth, high
      parental disapproval of smoking was protective against all three smoking
      behaviors whereas ethnic pride was not. For minority youth, the combined
      protective effect of higher ethnic pride and higher parental disapproval of
      smoking was protective against all smoking behaviors. CONCLUSION: The protective
      role of parental disapproval of smoking and ethnic pride on smoking behaviors may
      inform culturally sensitive smoking interventions aimed at diverse, multi-ethnic
      youth, and future studies are needed to examine this.

PMID- 22882394
TI  - Race/ethnicity differences between alcohol, marijuana, and co-occurring alcohol
      and marijuana use disorders and their association with public health and social
      problems using a national sample.
AB  - BACKGROUND: Alcohol and marijuana are commonly used and misused in the United
      States, both singly and together. Despite this, few studies examine their co
      occurring use and the corresponding association with public health and other
      problems. Moreover, there is a lack of investigation into differences in these
      associations on the basis of race/ethnicity. METHODS: The present study estimated
      the frequency of alcohol use disorder, marijuana use disorder, and co-occurring
      alcohol and marijuana use disorder and their associated public health and social
      problems in Whites, African Americans, and Hispanics. This cross-sectional study
      included 13,872 individuals and used data from the 2005-2007 National Survey on
      Drug Use and Health. Frequency was calculated and multinomial regression was used
      to assess associations between substance use disorder and psychosocial, adverse
      consequences such as history of being arrested, substance use treatment, and
      sexually transmitted infection. RESULTS: Alcohol use disorder was comparable
      between, and most prevalent among, Whites and Hispanics compared to African
      Americans, whereas marijuana use disorder was greatest among African Americans
      compared to other race/ethnicities. Co-occurring alcohol and marijuana use
      disorders were most prevalent for African Americans versus Whites and Hispanics,
      and similar in Whites and Hispanics. In general, major depressive episode was
      more prevalent for respondents with co-occurring use disorders or single
      marijuana use disorders. However, race/ethnicity differences in associations
      between substance use disorder and psychosocial correlates and adverse
      consequences were observed. CONCLUSIONS: Findings have implications for
      race/ethnicity appropriate integrated prevention and treatment of single and co
      occurring use disorders and psychiatric comorbidities.

PMID- 22882395
TI  - Substance use patterns among high-risk American Indians/Alaska Natives in Los
      Angeles County.
AB  - BACKGROUND: Substance abuse among American Indians/Alaska Natives (AI/ANs) is a
      significant and long-standing health problem in the U.S. Two-thirds of American
      AIs/ANs reside in the urban setting. However, studies analyzing substance use
      characteristics among urban AI/ANs are very limited. METHODS: Substance use
      patterns among a sample of AI/ANs (n = 77) and other ethnic/racial groups in Los
      Angeles County at high risk of substance abuse were analyzed utilizing three
      datasets from programs targeting individuals at high risk for substance abuse and
      risky sexual behaviors. RESULTS: Compared to all other ethnic/racial groups,
      AI/ANs demonstrated significantly younger age of onset of alcohol, marijuana,
      methamphetamine, and "other" drug use, higher correlations of age of first use of
      amphetamine with a measure of the drug's reinforcement, and higher mean number of
      illicit drug injections in the 30 days before being interviewed. CONCLUSIONS:
      Results from this study highlight a critical need for furthering our
      understanding of substance abuse problems among urban AI/ANs.

PMID- 22882396
TI  - A longitudinal examination of the relationships between childhood maltreatment
      and patterns of adolescent substance use among high-risk adolescents.
AB  - BACKGROUND: Childhood maltreatment has been linked to adolescent substance use in
      cross-sectional studies but the studies were unable to test the associations
      between childhood maltreatment and changes in substance use patterns during
      adolescence. The present study investigated the linkages between exposure to
      childhood maltreatment and developmental trends of alcohol, cannabis, cocaine,
      opioid, and hallucinogen use among high-risk adolescents. METHODS: We used a
      sample of 937 adolescents (mean age: 15.9 years; range: 13-18), who were selected
      from five publicly-funded service systems, to examine the extent to which
      childhood maltreatment may influence changes in patterns of adolescent substance
      use over time. RESULTS: The present study identified a 3-class model of
      adolescent substance use. Mover-stayer latent transition analyses (LTA) indicated
      that progression toward heavy polysubstance use increased with experience of
      childhood maltreatment. Findings also suggested that older male adolescents (ages
      15-18) who are involved with public service systems are at high risk for
      developing and maintaining multiple-substance use in adolescence. CONCLUSIONS:
      Experience of childhood maltreatment is associated with problematic patterns of
      adolescent substance use and may shape the longitudinal course of substance use
      during adolescence.

PMID- 22882397
TI  - Temperament and character modify risk of drug addiction and influence choice of
      drugs.
AB  - BACKGROUND: Drug addiction and alcoholism involve a complex etiopathogenesis with
      a variable degree of risk contributions from the host (person), environment, and
      addictive substances. In this work, temperament and character features of
      individuals addicted to opiates or alcohol are compared with normal controls to
      study personality factors in the overall risk for drug addiction. METHODS: The
      study was done in a permissive environment, with easy access to alcohol and
      heroin, which facilitated analyses of personality factors in drug choice.
      Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol
      addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade,
      Serbia, and a community sample of 346 controls. RESULTS: Opiate addicts
      manifested antisocial temperament configuration (high Novelty Seeking, low Reward
      Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy
      and imagination). Alcohol addicts manifested sensitive temperament configuration
      (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality
      was observed far more frequently in opiate addicts than in alcoholics or normals.
      CONCLUSIONS: Novelty Seeking appears to be a general risk factor for drug
      addiction. High Harm Avoidance appears to channel individuals with high Novelty
      Seeking towards alcoholism. Immature character traits and probable Personality
      Disorder increase the risk of illegal drugs. Based on equivalent research in
      nonpermissive environments, at least a portion of our opiate addicts could have
      developed alcoholism instead in environments with more limited access to opiates.
      Personality factors provide useful guidelines for preventive work with young
      individuals with personality risk factors for drug addiction.

PMID- 22882398
TI  - Employee assistance program services for alcohol and other drug problems:
      implications for increased identification and engagement in treatment.
AB  - BACKGROUND: Fourteen million U.S. workers meet the diagnostic criteria for
      substance dependence, costing millions in lost productivity. Prior research
      suggests that employees who follow through with their Employee Assistance
      Program's (EAP) recommendations are more likely to participate and remain engaged
      in alcohol and other drug (AOD) treatment programs. This study identified rates
      of lifetime EAP service use for AOD problems and compared adults who reported
      using EAP services for AOD problems with those who used services other than EAP.
      METHODS: Researchers analyzed a subset of participants from the National
      Epidemiologic Survey of Alcohol and Related Conditions who reported having
      received help for an AOD problem (NESARC, 2001-2002). Statistical analyses tested
      for differences in sociodemographic variables, lifetime mental health and
      substance abuse disorders, and health disability between EAP services users and
      users of other types of services. RESULTS: Among adults who sought services for
      AOD problems (n= 2,272), 7.58% (n= 166) reported using EAP services for these
      problems at some point during their lives. Major depressive disorder (lifetime),
      a drug use disorder (lifetime), and Black race/ethnicity were associated with a
      greater likelihood that someone would seek EAP services for help with their AOD
      problem. CONCLUSIONS: Results provide a foundation for researchers to understand
      who uses EAP services for AOD problems. Health and mental health professionals
      should increase their knowledge of EAP services to improve continuity of care for
      employees with AOD problems. EAPs are in a unique position to reach out to
      vulnerable employees in the workplace and engage them in treatment.

PMID- 22882399
TI  - Postprison release HIV-risk behaviors in a randomized trial of methadone
      treatment for prisoners.
AB  - BACKGROUND: This secondary analysis examined the impact of methadone initiated in
      prison on postrelease HIV risk behaviors. The parent study was a three-group
      randomized clinical trial in which participants received drug abuse counseling in
      prison and were randomly assigned to: (1) passive referral to substance abuse
      treatment upon release; (2) guaranteed methadone treatment admission upon
      release; and (3) methadone in prison and guaranteed continuation of methadone
      upon release. METHODS: Participants were 211 adult males with preincarceration
      histories of opiate dependence. The AIDS Risk Assessment was administered at
      baseline (in prison) and at 1-, 3-, 6-, and 12-month postrelease. Data were
      analyzed for the entire sample (N = 211) as well as the subsamples who reported
      injecting drugs in the 30 days prior to incarceration (n = 131) and who reported
      having unprotected sex in that time frame (n = 144) using generalized linear
      mixed model on an intent-to-treat basis. RESULTS: There were no significant
      changes in sex- or drug-risk by Condition over Time. There were significant Time
      and Condition main effects for the total sample as well as the injector subsample
      for drug-risk behaviors. There were no significant Condition main effects for HIV
      sex-risk behaviors, but there were significant Time main effects. CONCLUSIONS:
      Methadone initiated in prison or immediately postrelease is associated with
      reduced HIV drug-risk compared to counseling in prison without methadone and
      passive referral to treatment at release. Participation in several drug- and sex
      risk behaviors also showed significant declines during the postrelease time
      periods.

PMID- 22882400
TI  - Ready access to illicit drugs among youth and adult users.
AB  - BACKGROUND: Current drug-control strategies in Canada focus funding and resources
      predominantly on drug law enforcement, often at the expense of preventive,
      treatment, and harm reduction efforts. This study aimed to examine the
      availability of the most commonly used substances in Vancouver, Canada after the
      implementation of such strategies. METHODS: Using data from two large cohorts of
      drug-using youth and adults in Vancouver from the calendar year 2007, we assessed
      perceived availability of heroin, crack, cocaine, crystal methamphetamine, and
      marijuana. RESULTS: Compared to youth (n= 330), a greater proportion of adults
      (n= 1,160) reported immediate access (ie, within 10 minutes) to heroin (81.0% vs.
      55.9%, p < .001), crack (90.4% vs. 69.3%, p < .001), and cocaine (83.7% vs.
      61.1%, p < .001). Conversely, larger proportions of youth reported immediate
      access to crystal methamphetamine (62.8% vs. 39.4%, p < .001) and marijuana
      (88.4% vs. 73.2%, p < .001) compared to adult users. CONCLUSIONS: Regardless of
      differences in illicit drug availability by age, all drugs are readily accessed
      in Vancouver despite drug law enforcement efforts. This includes drugs that are
      frequently injected and place users at risk of human immunodeficiency virus (HIV)
      infection and transmission of other blood-borne disease.

PMID- 22882401
TI  - Buprenorphine compliance.

PMID- 22882402
TI  - Treatment of buprenorphine precipitated withdrawal: a case report.

PMID- 22882403
TI  - Buprenorphine/naloxone and dental caries: a case report.

PMID- 22882404
TI  - Complication of spice use in a deployed combat setting-seizure while on duty.

PMID- 22882407
TI  - IL1 gene polymorphisms in relation to external apical root resorption concurrent
      with orthodontia.
AB  - OBJECTIVE: External apical root resorption (EARR) is permanent shortening of the
      end of the tooth root. It is a common clinical complication of orthodontic
      treatment. Polymorphisms in the interleukin 1 (IL1) gene cluster have been
      related to an increased EARR risk. The aim of this study was to analyze possible
      associations of IL1 gene variants with EARR in Czech population. SUBJECTS AND
      METHODS: In this case-control study, 32 patients with EARR (age 15.0 +/- 4.1
      years) and 74 controls (age 15.2 +/- 5.3 years) were genotyped using PCR-based
      methods for IL1A (-889C/T), IL1B (+3953C/T), and IL1RN [IL1 receptor antagonist,
      variable number tandem repeat (VNTR)] gene polymorphisms. RESULTS: While no
      statistical significant differences in the IL1A and IL1B genotype, allele and
      reconstructed IL1 haplotype frequencies between patients with EARR and controls
      were found, marginally significant differences were observed in the frequencies
      of IL1RN variant (P = 0.05 for *22 genotype and P = 0.06 for a short (2) allele).
      In addition, significant associations between IL1RN*12, *22 genotypes and the
      short (2) allele and EARR were identified in the subgroup of girls (P = 0.04 and
      P = 0.02, P = 0.02). CONCLUSIONS: Although no significant role of IL1A (-889C/T)
      and IL1B (+3953C/T) variants in EARR was confirmed, IL1RN VNTR may be associated
      with EARR, especially in girls.

PMID- 22882408
TI  - Yersinia pestis versus Yersinia pseudotuberculosis: effects on host macrophages.
AB  - Yersinia pestis, the causative agent of plague, is proved to be a recently
      emerged clone from Y. pseudotuberculosis. However, the diseases they cause and
      their patterns of transmission are very different. People always focus on the
      genetic changes between Y. pestis and Y. pseudotuberculosis to reveal their
      pathogenic differences, and little is known about host defence differences to
      these two Yersinia. In this study, the effects of Y. pestis and Y.
      pseudotuberculosis on macrophages were analysed. Cell apoptosis showed
      significant difference after the macrophages were infected by these two strains,
      and caspase-3 activity also demonstrated a similar tendency. Further, macrophage
      function activities were evaluated. We found during the early infection of Y.
      pestis, several basic functions of macrophages, including phagocytosis, secretion
      of cytokine tumour necrosis factor-alpha and nitric oxide, macrophage polarity
      and antigen presenting, were significantly interrupted. In comparison, Y.
      pseudotuberculosis infection showed lower inhibition on macrophages. Especially,
      Y. pestis infection might cause macrophage to polarize to M2 macrophages in the
      early phase, compared with Y. pseudotuberculosis infection, which was different
      from the common acute infection. These results clearly indicated even in the
      early stage of infection, different host macrophage defence patterns could help
      us to understand the obvious virulence differences between Y. pestis and Y.
      pseudotuberculosis.

PMID- 22882409
TI  - Mesenchymal stem cells derived from human induced pluripotent stem cells modulate
      T-cell phenotypes in allergic rhinitis.
AB  - BACKGROUND: Human induced pluripotent stem cells (iPSCs) possess remarkable self
      renewal capacity and the potential to differentiate into novel cell types, such
      as mesenchymal stem cells (MSCs). iPSC-MSCs have been shown to enhance tissue
      regeneration and attenuate tissue ischaemia; however, their contribution to the
      immune regulation of Th2-skewed allergic rhinitis (AR) and asthma remains
      unclear. OBJECTIVE: This study compared the immunomodulatory effects of iPSC-MSCs
      and bone marrow-derived MSCs (BM-MSCs) on lymphocyte proliferation, T-cell
      phenotypes and cytokine production in peripheral blood mononuclear cells (PBMCs)
      in patients with AR, and investigated the possible molecular mechanisms
      underlying the immunomodulatory properties of iPSC-MSCs. METHODS: In co-cultures
      of PBMCs with iPSC-MSCs or BM-MSCs, lymphocyte proliferation was evaluated using
      3H-thymidine (3H-TdR) uptake, carboxyfluorescein diacetate, succinimidyl ester
      (CFDA-SE) assays; the regulatory T-cell (Treg) phenotype was determined by flow
      cytometry, and cytokine levels were measured using an enzyme-linked immunosorbent
      assay. The immunomodulatory properties of both MSCs were further evaluated using
      NS398 and transwell experiments. RESULTS: Similar to BM-MSCs, we determined that
      iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg
      response in PBMCs (P < 0.05). Accordingly, the cytokine milieu (IFN-gamma, IL-4,
      IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (P <
      0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated
      with prostaglandin E2 (PGE2) production and cell-cell contact. CONCLUSIONS: These
      data demonstrate that iPSC-MSCs are capable of modulating T-cell phenotypes
      towards Th2 suppression through inducing Treg expansion, suggesting that iPSC
      MSCs can be used as an alternative candidate to adult MSCs to treat allergic
      airway diseases.

PMID- 22882410
TI  - Evidence-based practice models for organizational change: overview and practical
      applications.
AB  - AIM: To provide an overview, summary of key features and evaluation of usefulness
      of six evidence-based practice models frequently discussed in the literature.
      BACKGROUND: The variety of evidence-based practice models and frameworks, complex
      terminology and organizational culture challenges nurses in selecting the model
      that best fits their practice setting. DATA SOURCES: The authors: (1) initially
      identified models described in a predominant nursing text; (2) searched the
      literature through CINAHL from 1998 to current year, using combinations of
      'evidence', 'evidence-based practice', 'models', 'nursing' and 'research'; (3)
      refined the list of selected models based on the initial literature review; and
      (4) conducted a second search of the literature on the selected models for all
      available years to locate both historical and recent articles on their use in
      nursing practice. DISCUSSION: Authors described model key features and provided
      an evaluation of model usefulness based on specific criteria, which focused on
      facilitating the evidence-based practice process and guiding practice change.
      IMPLICATIONS FOR NURSING: The evaluation of model usefulness can be used to
      determine the best fit of the models to the practice setting. CONCLUSION: The
      Johns Hopkins Model and the Academic Center for Evidence-Based Practice Star
      Model emphasize the processes of finding and evaluating evidence that is likely
      to appeal to nursing educators. Organizations may prefer the Promoting Action on
      Research Implementation in Health Services Framework, Advancing Research and
      Clinical Practice Through Close Collaboration, or Iowa models for their emphasis
      on team decision-making. An evidence-based practice model that is clear to the
      clinician and fits the organization will guide a systematic approach to evidence
      review and practice change.

PMID- 22882411
TI  - An assessment of a new navigatable percutaneous disc decompression device
      (l'DISQ) through histologic evaluation and thermo-mapping in human cadaveric
      discs.
AB  - STUDY DESIGN: This is an in vitro experimental study of the technical capability
      and safety study of a navigable percutaneous disc decompression device named
      L'DISQ. OBJECTIVES: The objectives of this study were to determine if L'DISQ
      could adequately reach certain target zones in the disc and to measure the
      distribution of rises in temperature in the surrounding tissue when the device
      was used to ablate the disc. METHODS: Placement of the wand of L'DISQ was
      attempted into the posterior annulus of the discs of four fresh human cadavers.
      During disc ablation, thermocouple probes were used to measure the temperature
      within the nucleus pulposus and annulus fibrosus, on the surface of the annulus,
      and on the posterior longitudinal ligament. Tissues harvested from around the
      disc were examined histologically. RESULTS: The tip of the wand could be
      successfully navigated to the posterolateral or posterocentral annulus at all
      levels above L5-S1 using a lateral approach. Rises in temperature did not exceed
      13.25 +/- 0.84 degrees C within the disc, and did not exceed 1 degrees C on the
      surface of the disc. Histology demonstrated no thermal damage to the surrounding
      neural tissues. CONCLUSION: L'DISQ can be successfully navigated to the target
      zones, and disc tissue ablated without thermal or structural damage to the
      adjacent neural tissues.

PMID- 22882412
TI  - Management of recurrent leaks following postinfarction ventricular septal defect
      repairs.
AB  - Ventricular septal rupture (VSR) complicates acute myocardial infarction (AMI) in
      less than 0.2% of cases and is usually surgically managed by endocardial patch
      repair with infarct exclusion. Although successful in 80% of cases, failure of
      patch repair (often because of patch dehiscence) results in attempts at
      percutaneous closure as reoperative mortality can be as high as 40%. We describe
      a case of an AMI in a 63-year-old male with resultant VSR that required repeat
      surgical patch repair secondary to recurrent leak. We discuss the management of
      recurrent leaks and surgical techniques aimed at decreasing residual defects.

PMID- 22882413
TI  - Technophobia.

PMID- 22882414
TI  - Molar tooth sign. Joubert syndrome.

PMID- 22882415
TI  - Paroxysmal cold haemoglobinuria in an 18-month-old child during an Australian
      spring.

PMID- 22882416
TI  - Pneumocephalus as a complication of nasal oxygen inhalation.

PMID- 22882417
TI  - Glutaric aciduria type 1 presenting as subdural haematoma.

PMID- 22882420
TI  - Highly pigmented Tg(Grm1) mouse melanoma develops non-pigmented melanoma cells in
      distant metastases.
AB  - Murine model systems are critically required tools for the investigation of
      unknown mechanisms of melanoma development and metastasis and for developing more
      efficient therapies. The Tg(Grm1)EPv melanoma mouse model is characterized by
      spontaneous development of pigmented cutaneous melanomas at hairless skin
      regions, with a short latency and 100% penetrance. Local metastasis was described
      in initial analyses; however, melanoma cells were not observed in distant organs.
      Here, we demonstrate that the established Tg(Grm1)EPv melanoma mouse model
      exhibits more extensive metastasis into distant organs than previously described.
      Disseminated cells undergo phenotypic changes, as we observed high numbers of non
      pigmented Grm1-expressing melanoma cells within distant organs. As such changes
      during metastasis are common in human melanoma, our findings demonstrate that
      this mouse model represents an even more useful tool to study unknown mechanisms
      of metastasis in human melanoma than previously assumed.

PMID- 22882421
TI  - Hereditary angioedema: first report of the Brazilian registry and challenges.
AB  - BACKGROUND: Hereditary Angio-oedema (HAE) is a serious medical condition caused
      by a rare autosomal dominant genetic disorder, in which C1 inhibitor (C1-INH)
      function is reduced. There is no organized information on the HAE patient
      population in Brazil. OBJECTIVE: The Brazilian Registry was established to
      disseminate diagnostic access, and to better understand the main features of the
      disease in our country and its clinical impact. METHODS: A questionnaire was
      prepared and sent to specialists. The completed questionnaires were forwarded to
      the coordinating site and then entered into the Registry. Samples from patients
      with an unconfirmed diagnosis were tested for C1 inhibitor and C4 levels.
      RESULTS: From 2006 to 2010, 210 patients (133 females; mean age, 30 +/-17 years)
      were included. The median age of onset of symptoms and age at diagnosis were 6.5
      and 21 years, respectively; 80.9% of the patients had subcutaneous oedema, 54%
      gastrointestinal and 35.7% respiratory symptoms (21% had laryngeal oedema).
      Laparotomy due to the disease was performed in 6.2% of the patients. The majority
      of patients had Type I HAE of moderate severity. Twenty-seven per cent did not
      receive treatment; 53% were treated with danazol alone. CONCLUSION: A paucity of
      patients with Type II HAE and a high frequency of laparotomy were observed,
      highlighting the need for better diagnosis in Brazil. HAE related educational
      activities, improved diagnosis and access to available therapy are needed in
      Brazil.

PMID- 22882422
TI  - The relationship between post-thaw sperm DNA integrity and non-return rate among
      Norwegian cross-bred rams.
AB  - With the aim of investigating the relationship between sperm DNA integrity and
      non-return rate (NRR) among Norwegian cross-bred rams, semen from 15 individuals
      was examined by flow cytometry. Sperm Chromatin Structure Assay (SCSA) quantifies
      the proportion of spermatozoa with denatured DNA after in situ acid treatment,
      and the four parameters % DFI, % HDS, MEAN DFI and SD DFI are all different
      measures of DNA denaturation and maturation. Field fertility, reported as NRR 25
      days after insemination was based on all inseminations from a large-scale
      breeding programme and supplied by the Norwegian Association of Sheep and Goat
      Farmers. From each ram, four straws from four different weeks of the breeding
      season were analysed, and the associations between 25-day NRR and the mean of the
      four SCSA parameters were tested using a logistic regression model. The results
      revealed no association between fertility and % DFI or % HDS, while SD DFI and
      MEAN DFI showed a significant negative association with NRR. Further, the SCSA
      values varied significantly between ejaculates within ram among some of the rams
      in the study. However, no significant association was seen between these intra
      individual differences in sperm DNA integrity and NRR. In conclusion, this study
      suggests an association between sperm DNA integrity and NRR for rams. However,
      further research must be conducted to confirm these findings and determine
      whether sperm DNA assessments can be applied to predict ram fertility.

PMID- 22882424
TI  - Multisynaptic projections from the ventrolateral prefrontal cortex to the dorsal
      premotor cortex in macaques - anatomical substrate for conditional visuomotor
      behavior.
AB  - Lines of evidence indicate that both the ventrolateral prefrontal cortex (vlPFC)
      (areas 45/12) and dorsal premotor cortex (PMd) (rostral F2 in area 6) are
      crucially involved in conditional visuomotor behavior, in which it is required to
      determine an action based on an associated visual object. However, virtually no
      direct projections appear to exist between the vlPFC and PMd. In the present
      study, to elucidate possible multisynaptic networks linking the vlPFC to the PMd,
      we performed a series of neuroanatomical tract-tracing experiments in macaque
      monkeys. First, we identified cortical areas that send projection fibers directly
      to the PMd by injecting Fast Blue into the PMd. Considerable retrograde labeling
      occurred in the dorsal prefrontal cortex (dPFC) (areas 46d/9/8B/8Ad), dorsomedial
      motor cortex (dmMC) (F7 and presupplementary motor area), rostral cingulate motor
      area, and ventral premotor cortex (F5 and area 44), whereas the vlPFC was
      virtually devoid of neuronal labeling. Second, we injected the rabies virus, a
      retrograde transneuronal tracer, into the PMd. At 3 days after the rabies
      injections, second-order neurons were labeled in the vlPFC (mainly area 45),
      indicating that the vlPFC disynaptically projects to the PMd. Finally, to
      determine areas that connect the vlPFC to the PMd indirectly, we carried out an
      anterograde/retrograde dual-labeling experiment in single monkeys. By examining
      the distribution of axon terminals labeled from the vlPFC and cell bodies labeled
      from the PMd, we found overlapping labels in the dPFC and dmMC. These results
      indicate that the vlPFC outflow is directed toward the PMd in a multisynaptic
      fashion through the dPFC and/or dmMC.

PMID- 22882426
TI  - Occurrence of infection among children with nephrotic syndrome during
      hospitalizations.
AB  - AIM: The present study was conducted to investigate the trends of childhood
      nephrotic syndrome (NS) admissions and factors associated with childhood NS
      admissions with major infections in Taiwan. METHODS: A retrospective analysis was
      performed using Taiwan National Health Research Insurance Database (NHIRD) to
      explore the associated factors and health care burden for childhood NS admissions
      with major infections in 1997 to 2007. RESULTS: Of 133,927 children, a total of
      176 children had NS, which incurred 508 hospital admissions. Nineteen percent of
      admissions were associated with major infections. Pneumonia was the most common
      infection (49%), followed by urinary tract infection (UTI), bacteraemia/sepsis,
      peritonitis and cellulitis. Pneumonia was the most common infection among
      children age younger than 10 years, whereas UTI was more common among children
      aged greater than 10 years. NS admission with infections had longer periods of
      hospital length of stay and higher hospital total costs compared to those without
      infections. Regression analysis reveals that younger age, regional hospitals,
      admission hospital located in middle and south areas and admission made in spring
      were associated with increased risk for developing major infections. CONCLUSIONS:
      While 19% of childhood NS admissions were associated with major infections, young
      age, admissions made in spring, located in middle and south Taiwan and in
      regional hospitals were the major associated factors for infection. Age plays an
      important role in risk and types of infection.

PMID- 22882427
TI  - Reinforcements arrive for the war against chronic cystitis and bladder cancer.

PMID- 22882428
TI  - Long-term oral mesalazine adherence and the risk of disease flare in ulcerative
      colitis: nationwide 10-year retrospective cohort from the veterans affairs
      healthcare system.
AB  - BACKGROUND: Adherence is a major factor in determining disease activity in
      ulcerative colitis (UC). There are limited data on long-term nationwide adherence
      levels among patients with UC. AIM: To evaluate the long-term adherence levels to
      oral mesalazine (mesalamine) in the Veterans Affairs (VA) healthcare system, to
      determine the impact of non-adherence on the risk of flares, and to evaluate the
      different pharmacy data-based adherence indicators. METHODS: Nationwide data were
      obtained from the VA for the period 2001-2011. UC patients who started mesalazine
      maintenance during the inclusion period were included. Level of adherence was
      assessed using three different indicators: medication possession ratio (MPR),
      continuous single-interval medication availability (CSA) and continuous multiple
      interval medication gaps (CMG). Cox regression modelling was used to predict
      disease flares and assess the predictive value of each adherence indicator.
      RESULTS: We included 13 062 patients into the analysis with median follow-up time
      of 6.1 years. Percentage of patients with high adherence was 47%, 43%, 31% as
      identified by CSA, MPR and CMG respectively. Low adherers had a significant
      increase in the risk of flares compared with high adherers (Hazard ratio: 2.8,
      1.7 and 1.8, P < 0.001 for CSA, MPR and CMG, respectively). Compared with other
      adherence indicators, CSA offered the best trend in predicting disease flares.
      CONCLUSIONS: Long-term high-adherence level was lower than previously reported.
      Adherence was a significant factor in predicting disease flares. Pharmacy
      adherence indicators may be useful to healthcare providers in identifying
      patients at high risk of exacerbations.

PMID- 22882429
TI  - Viral vectors for targeting the canine retina: a review.
AB  - Clinical trials are currently underway using gene therapy to treat retinal
      disease such as Leber congenital amaurosis (LCA). Viral vectors that have been
      utilized to target retinal cells include adenoviruses, lentiviruses, and
      recombinant adeno-associated viruses (rAAV). Of the three classes, rAAV vectors
      show the greatest promise for retinal gene therapy. Recent developments in virus
      technology such as the development of hybrid and capsid mutant rAAV vectors mean
      that specific retinal cells can be targeted and faster stronger transgene
      expression is now possible compared to that achieved with the first generation of
      vectors. Gene therapy trials in dogs have been very important in the development
      of therapy for RPE65 LCA which is currently in phase I/II clinical trials in
      humans. Recent successes in using gene therapy to treat canine achromatopsia, X
      linked progressive retinal atrophy (PRA) and the more severe rapid degenerations
      such as rod-cone dysplasia type 3 may lead also to the translation to human
      clinical trials. Dogs have played and continue to play an important role as
      animal models for proof-of-concept studies of retinal gene therapy. As
      modifications and improvements in gene therapy protocols are made from experience
      gathered from human clinical trials perhaps gene therapy for the treatment of
      canine clinical patients will become available to veterinary ophthalmologists.

PMID- 22882425
TI  - Vascular effects of dietary nitrate (as found in green leafy vegetables and
      beetroot) via the nitrate-nitrite-nitric oxide pathway.
AB  - The discovery that dietary (inorganic) nitrate has important vascular effects
      came from the relatively recent realization of the 'nitrate-nitrite-nitric oxide
      (NO) pathway'. Dietary nitrate has been demonstrated to have a range of
      beneficial vascular effects, including reducing blood pressure, inhibiting
      platelet aggregation, preserving or improving endothelial dysfunction, enhancing
      exercise performance in healthy individuals and patients with peripheral arterial
      disease. Pre-clinical studies with nitrate or nitrite also show the potential to
      protect against ischaemia-reperfusion injury and reduce arterial stiffness,
      inflammation and intimal thickness. However, there is a need for good evidence
      for hard endpoints beyond epidemiological studies. Whilst these suggest reduction
      in cardiovascular risk with diets high in nitrate-rich vegetables (such as a
      Mediterranean diet), others have suggested possible small positive and negative
      associations with dietary nitrate and cancer, but these remain unproven.
      Interactions with other nutrients, such as vitamin C, polyphenols and fatty acids
      may enhance or inhibit these effects. In order to provide simple guidance on
      nitrate intake from different vegetables, we have developed the Nitrate 'Veg
      Table' with 'Nitrate Units' [each unit being 1 mmol of nitrate (62 mg)] to
      achieve a nitrate intake that is likely to be sufficient to derive benefit, but
      also to minimize the risk of potential side effects from excessive ingestion,
      given the current available evidence. The lack of data concerning the long term
      effects of dietary nitrate is a limitation, and this will need to be addressed in
      future trials.

PMID- 22882430
TI  - Oral food desensitization in children with IgE-mediated hen's egg allergy: a new
      protocol with raw hen's egg.
AB  - BACKGROUND: Hen's egg allergy affects young children and can cause severe
      allergic reactions. Avoidance results in dietary limitations and can affect the
      quality of life, especially in cases where potentially life-threatening reactions
      exist. Our objective was to desensitize children with moderate-severe IgE
      mediated hen's egg allergy over a 6-month period, by introducing increasing and
      very gradual daily doses of raw hen's egg in order to enable the children to
      assume 25ml of this food, or to induce tolerance to the highest possible dose.
      The protocol foresaw the egg reintroduction in the home setting. METHODS: In this
      randomized, controlled open study, 20 hen's egg allergic children (10 in the
      active group) were admitted. A convincing history or a positive double-blind
      placebo-controlled food challenge confirmed the diagnosis. Oral desensitization
      was performed with increasing doses starting from 0.27 mg of hen's egg proteins
      (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically
      calculated protocol in order to ensure a constant, daily increment of doses.
      RESULTS: 8/10 children (80%) in the active group achieved the daily intake of
      25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while
      another child (10%) failed the desensitization. Six months after enrolment only 2
      children in the control group (20%) could tolerate hen's egg. CONCLUSIONS: We
      successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a
      6-month period. The partial outcome in the child who could tolerate 2ml/day
      reduced the risk of severe reactions after unnoticed introduction of egg. A
      regular protocol that ensures a daily constant increase of doses helps to reduce
      possible adverse events, thus improving safety and effectiveness.

PMID- 22882431
TI  - Transfusion-related biologic effects and free hemoglobin, heme, and iron.
AB  - BACKGROUND: Red blood cell (RBC) transfusion is common in intensive care unit
      (ICU) patients and is associated with complications that appear related to the
      duration of blood storage. We hypothesize that hemolysis of stored RBCs results
      in increases in the availability of non-heme-bound iron, which inhibits
      macrophage activation. STUDY DESIGN AND METHODS: RBCs were sampled at multiple
      time points to evaluate hemolysis and iron release. Activation of THP-1 monocytic
      cells was assessed in the presence of plasma from aged RBCs. Age of transfused
      blood in our pediatric intensive care unit (PICU) from 2001 to 2006 was analyzed
      to assess relevance to our patient population. RESULTS: Hemolysis increased
      significantly during storage time as demonstrated by increases in free heme and
      hemoglobin. While there was a trend toward elevated levels of non-heme-bound
      iron, this was not significant (p = 0.07). THP-1 cell activation was inhibited by
      exposures to both plasma and a ferric compound; the effect of plasma on
      macrophage activation was not reversed by the iron chelator desferroxamine.
      Thirty-one percent of our PICU patients received blood older than 2 weeks.
      CONCLUSION: Hemolysis products increased significantly over time in our stored
      RBCs. Ferric compounds and plasma from stored blood inhibit THP-1 cell
      activation. Plasma inhibition does not appear to be due primarily to increased
      iron. Further studies are needed to define the inhibitory effect of stored blood
      plasma on macrophage function. Complications related to blood storage are
      relevant to our PICU patients.

PMID- 22882432
TI  - Suppression of liver regeneration affects hepatic graft survival in small-for
      size liver transplantation in rats.
AB  - AIM:   Small-for-size liver transplantation (SFSLT) often results in hepatic
      graft failure and decreased survival. The present study was aimed to investigate
      the possible mechanism of hepatic graft failure in SFSLT in rats. METHODS:   Rat
      models of full-size orthotopic liver transplantation, 50% partial liver
      transplantation and 30% partial liver transplantation were established.
      Proliferative responses of the hepatic graft were evaluated by
      immunohistochemical staining and western blotting. Apoptosis-, inflammatory-,
      anti-inflammatory- and growth factor-related genes were screened by quantitative
      reverse transcription polymerase chain reaction. Activities of transcription
      factors of AP-1 and nuclear factor (NF)-kappaB were analyzed by electrophoretic
      mobility shift assay. RESULTS:   A 30% partial liver transplant not only resulted
      in marked structural damages to the hepatic graft, but also showed the lowest 7
      day survival rate. In addition, sup pressed expressions of proliferating cell
      nuclear antigen (PCNA) and cyclin D1 by immunohistochemical staining and
      decreased expressions of cyclin D1 and p-c-Jun by western blotting were detected.
      Downregulated expressions of Bcl-2, Bcl-XL, interleukin (IL)-6, IL-10, IP-10 and
      CXCR2, upregulated expression of tumor necrosis factor-alpha, and decreased
      levels of AP-1 and NF-kappaB were also found following 30% partial liver
      transplantation after reperfusion. CONCLUSION:   Liver regeneration is remarkably
      suppressed in SFSLT. The significant changes of intra-graft gene expression
      described above indicated that ischemia reperfusion injury would be severe in 30%
      partial liver transplantation. The capability of liver regeneration secondary to
      ischemia reperfusion injury might determine hepatic graft survival in SFSLT.

PMID- 22882433
TI  - Modelling in vivo skeletal muscle ageing in vitro using three-dimensional
      bioengineered constructs.
AB  - Degeneration of skeletal muscle (SkM) with age (sarcopenia) is a major
      contributor to functional decline, morbidity and mortality. Methodological
      implications often make it difficult to embark on interventions in already frail
      and diseased elderly individuals. Using in vitro three-dimensional (3D)
      bioengineered skeletal muscle constructs that model aged phenotypes and
      incorporate a representative extracellular matrix (collagen), are under tension,
      and display morphological and transcript expression of mature skeletal muscle may
      more accurately characterize the SkM niche. Furthermore, an in vitro model would
      provide greater experimental manipulation with regard to gene, pharmacological
      and exercise (mechanical stretch/electrical stimulation) therapies and thus
      strategies for combating muscle wasting with age. The present study utilized
      multiple population-doubled (MPD) murine myoblasts compared with parental
      controls (CON), previously shown to have an aged phenotype in monolayer cultures
      (Sharples et al., 2011), seeded into 3D type I collagen matrices under uniaxial
      tension. 3D bioengineered constructs incorporating MPD cells had reduced myotube
      size and diameter vs. CON constructs. MPD constructs were characterized by
      reduced peak force development over 24 h after cell seeding, reduced transcript
      expression of remodelling matrix metalloproteinases, MMP2 and MMP9, with reduced
      differentiation/hypertrophic potential shown by reduced IGF-I, IGF-IR, IGF-IEa,
      MGF mRNA. Increased IGFBP2 and myostatin in MPD vs. CON constructs also suggested
      impaired differentiation/reduced regenerative potential. Overall, 3D
      bioengineered skeletal muscle constructs represent an in vitro model of the in
      vivo cell niche with MPD constructs displaying similar characteristics to
      ageing/atrophied muscle in vivo, thus potentially providing a future test bed for
      therapeutic interventions to contest muscle degeneration with age.

PMID- 22882434
TI  - First successful bridge to transplantation with the total artificial heart.

PMID- 22882435
TI  - Summary of the 19th Congress of the International Society for Rotary Blood Pumps.

PMID- 22882436
TI  - Respect the history and foresee the future: milestones of the International
      Society for Rotary Blood Pumps with Artificial Organs.

PMID- 22882437
TI  - Blood trauma testing of CentriMag and RotaFlow centrifugal flow devices: a pilot
      study.
AB  - Mechanical circulatory assist devices that provide temporary support in heart
      failure patients are needed to enable recovery or provide a bridge to decision.
      Minimizing risk of blood damage (i.e., hemolysis) with these devices is critical,
      especially if the length of support needs to be extended. Hematologic responses
      of the RotaFlow (Maquet) and CentriMag (Thoratec) temporary support devices were
      characterized in an in vitro feasibility study. Paired static mock flow loops
      primed with fresh bovine blood (700 mL, hematocrit [Hct] = 25 +/- 3%, heparin
      titrated for activated clotting time >300 s) pooled from a single-source donor
      were used to test hematologic responses to RotaFlow (n = 2) and CentriMag (n = 2)
      simultaneously. Pump differential pressures, temperature, and flow were
      maintained at 250 +/- 10 mm Hg, 25 +/- 2 degrees C, and 4.2 +/- 0.25 L/min,
      respectively. Blood samples (3 mL) were collected at 0, 60, 120, 180, 240, 300,
      and 360 min after starting pumps in accordance with recommended Food and Drug
      Administration and American Society for Testing and Materials guidelines. The
      CentriMag operated at a higher average pump speed (3425 rpm) than the RotaFlow
      (3000 rpm) while maintaining similar constant flow rates (4.2 L/min). Hematologic
      indicators of blood trauma (hemoglobin, Hct, platelet count, plasma free
      hemoglobin, and white blood cell) for all measured time points as well as
      normalized and modified indices of hemolysis were similar (RotaFlow: normalized
      index of hemolysis [NIH] =  0.021 +/- 0.003 g/100 L, modified index of hemolysis
      [MIH] = 3.28 +/- 0.52 mg/mg compared to CentriMag: NIH =  0.041 +/- 0.010 g/100
      L, MIH = 6.08 +/- 1.45 mg/mg). In this feasibility study, the blood trauma
      performance of the RotaFlow was similar or better than the CentriMag device under
      clinically equivalent, worst-case test conditions. The RotaFlow device may be a
      more cost-effective alternative to the CentriMag.

PMID- 22882438
TI  - Passive control of a biventricular assist device with compliant inflow cannulae.
AB  - Rotary ventricular assist device (VAD) support of the cardiovascular system is
      susceptible to suction events due to the limited preload sensitivity of these
      devices. This may be of particular concern with rotary biventricular support
      (BiVAD) where the native, flow balancing Starling response is diminished in both
      ventricles. The reliability of sensor and sensorless-based control systems which
      aim to control VAD flow based on preload has limitations, and, thus, an
      alternative solution is desired. This study introduces a compliant inflow cannula
      (CIC) which could improve the preload sensitivity of a rotary VAD by passively
      altering VAD flow depending on preload. To evaluate the design, both the CIC and
      a standard rigid inflow cannula were inserted into a mock circulation loop to
      enable biventricular heart failure support using configurations of atrial and
      ventricular inflow, and arterial outflow cannulation. A range of left (LVAD) and
      right VAD (RVAD) rotational speeds were tested as well as step changes in
      systemic/pulmonary vascular resistance to alter relative preloads, with resulting
      flow rates recorded. Simulated suction events were observed, particularly at
      higher VAD speeds, during support with the rigid inflow cannula, while the CIC
      prevented suction events under all circumstances. The compliant section passively
      restricted its internal diameter as preload was reduced, which increased the VAD
      circuit resistance and thus reduced VAD flow. Therefore, a CIC could potentially
      be used as a passive control system to prevent suction events in rotary left,
      right, and biventricular support.

PMID- 22882439
TI  - Development of a pump flow estimator for rotary blood pumps to enhance monitoring
      of ventricular function.
AB  - Estimation of instantaneous flow in rotary blood pumps (RBPs) is important for
      monitoring the interaction between heart and pump and eventually the ventricular
      function. Our group has reported an algorithm to derive ventricular contractility
      based on the maximum time derivative (dQ/dt(max)  as a substitute for ventricular
      dP/dt(max) ) and pulsatility of measured flow signals. However, in RBPs used
      clinically, flow is estimated with a bandwidth too low to determine dQ/dt(max) 
      in the case of improving heart function. The aim of this study was to develop a
      flow estimator for a centrifugal pump with bandwidth sufficient to provide
      noninvasive cardiac diagnostics. The new estimator is based on both static and
      dynamic properties of the brushless DC motor. An in vitro setup was employed to
      identify the performance of pump and motor up to 20 Hz. The algorithm was
      validated using physiological ventricular and arterial pressure waveforms in a
      mock loop which simulated different contractilities (dP/dt(max)  600 to 2300 mm
      Hg/s), pump speeds (2 to 4 krpm), and fluid viscosities (2 to 4 mPa.s). The
      mathematically estimated pump flow data were then compared to the datasets
      measured in the mock loop for different variable combinations (flow ranging from
      2.5 to 7 L/min, pulsatility from 3.5 to 6 L/min, dQ/dt(max)  from 15 to 60
      L/min/s). Transfer function analysis showed that the developed algorithm could
      estimate the flow waveform with a bandwidth up to 15 Hz (+/-2 dB). The mean
      difference between the estimated and measured average flows was +0.06 +/- 0.31
      L/min and for the flow pulsatilities -0.27 +/- 0.2 L/min. Detection of dQ/dt(max)
      was possible up to a dP/dt(max)  level of 2300 mm Hg/s. In conclusion, a flow
      estimator with sufficient frequency bandwidth and accuracy to allow determination
      of changes in ventricular contractility even in the case of improving heart
      function was developed.

PMID- 22882440
TI  - Temporary right heart assist: a minimally invasive approach.
AB  - A surgical method for the implantation of a mechanical right ventricular assist
      device which avoids resternotomy/thoracotomy and related complications at the
      time of explantation is presented. In order to support the failing right heart, a
      Dacron vascular graft was sewn to the pulmonary artery. For venous drainage, a
      cannula was inserted into the right atrium via the femoral vein. Explantation of
      the system, after the right heart resumed its function, was accomplished by
      retracting and compressing the venous cannula in the groin as well as by
      retracting the arterial cannula from the Dacron vascular graft followed by
      suturing without opening the chest. Between 2006 and 2011, this system was used
      in 12 patients. The median duration of right heart support was 10.5 days. Seven
      patients were successfully weaned from the system, six patients survived. In all
      cases, explantation was free of complications. The technique described is a safe
      method to support the right heart and allows explantation without the risks and
      complications of reopening the thorax.

PMID- 22882441
TI  - Analysis of flow within a left ventricle model fully assisted with continuous
      flow through the aortic valve.
AB  - Blood compatibility of a ventricular assist device (VAD) depends on the dynamics
      of blood flow. The focus in most previous studies was on blood flow in the VAD.
      However, the tip shape and position of the VAD inflow cannula influence the
      dynamics of intraventricular blood flow and thus thrombus formation in the
      ventricle. In this study, blood flow in the left ventricle (LV) under support
      with a catheter-type continuous flow blood pump was investigated. The flow field
      was analyzed both numerically and experimentally to investigate the effects of
      catheter tip shape and its insertion depth on intraventricular flow patterns. A
      computational model of the LV cavity with a simplified shape was constructed
      using computer-aided design software. Models of catheters with three different
      tip shapes were constructed and each was integrated to the LV model. In addition,
      three variations of insertion depth were prepared for all models. The fully
      supported intraventricular flow field was calculated by computational fluid
      dynamics (CFD). A transparent LV model made of silicone was also fabricated to
      analyze the intraventricular flow field by the particle image velocimetry
      technique. A mock circulation loop was constructed and water containing tracer
      particles was circulated in the loop. The motion of particles in the LV model was
      recorded with a digital high-speed video camera and analyzed to reveal the flow
      field. The results of numerical and experimental analyses indicated the formation
      of two large vortices in the bisector plane of the mitral and aortic valve
      planes. The shape and positioning of the catheter tip affected the flow
      distribution in the LV, and some of these combinations elongated the upper vortex
      toward the ventricular apex. Assessment based on average wall shear stress on the
      LV wall indicated that the flow distribution improved the washout effect. The
      flow patterns obtained from flow visualization coincided with those calculated by
      CFD analysis. Through these comparisons, the numerical analysis was validated. In
      conclusion, results of these numerical and experimental analyses of flow field in
      the LV cavity provide useful information when designing catheter-type VADs.

PMID- 22882442
TI  - Reevaluation of the Harboe assay as a standardized method of assessment for the
      hemolytic performance of ventricular assist devices.
AB  - The Harboe spectrophotometric assay is regarded as one of the safest and most
      reproducible methods for measuring plasma free hemoglobin (pfHb). However, there
      is still some ambiguity in the application of the assay when assessing the
      hemolytic performance of ventricular assist devices (VADs). The purpose of this
      study was to reexamine and compare values of pfHb obtained using different
      concentrations of plasma diluent (Na(2) CO(3) ) as cited by various studies such
      that a standard practice may be recommended for the application of the Harboe
      assay in the hemolytic evaluation of VADs, allowing reliable comparisons to be
      made between laboratories. As a means to examine the Harboe assay, a BioMedicus
      BPX-80 was tested using both whole blood and a washed suspension of red blood
      cells (RBCs). Results show that for whole blood, the pfHb may be underestimated
      by 13-23%, dependent upon the concentration of Na(2) CO(3)  diluent solution.
      This trend was not observed for the washed suspension of RBCs. Furthermore, it is
      shown that the concentration of diluent influences the stability of a sample. The
      results of this study show that the problems associated with the incongruity of
      pfHb readings are a direct result of the precipitation of proteins from the
      plasma under alkaline conditions; as the molarity of the diluent controls pH, it
      becomes essential to use the appropriate concentration of Na(2) CO(3)  diluent in
      order to avoid turbidity of the solution and the consequent misrepresentation of
      pfHb values. Such standardization is pertinent when measuring the very low levels
      of pfHb observed during the in vivo testing of modern ventricular assist devices.

PMID- 22882444
TI  - Implementation of cerebral autoregulation into computational fluid dynamics
      studies of cardiopulmonary bypass.
AB  - Peri- or postoperative neurological complications are among the main risks for
      patients undergoing extracorporeal circulatory support (ECC). Two of the main
      reasons are an increased risk for strokes and altered flow conditions leading to
      cerebral hypoperfusion. This is strongly affected by cerebral autoregulation,
      which is the body's intrinsic ability to provide sufficient cerebral blood flow
      (CBF) despite changes in cerebral perfusion pressure (CPP). This complex
      mechanism has been mainly neglected in numerical studies, which have often been
      applied for analysis of ECC. In this study, a mathematical model is presented to
      implement cerebral autoregulation into computational fluid dynamics (CFD)
      studies. CFD simulations of cardiopulmonary bypass (CPB) were performed in a 3D
      model of the cardiovascular system, with flow variations between 4.5-6 L/min.
      Cerebral outlets were modeled using an equation to calculate CBF based on CPP.
      Assuming full regulation, CBF was kept constant for CPP between 80 and 120 mm Hg.
      A deviation in CBF of 20% occurred for CPP between 55-80 mm Hg and 120-145 mm Hg,
      respectively. The level of regulation was varied to take possible impairment of
      cerebral autoregulation into account. Furthermore, chronic hypertension was
      modeled by increasing the baseline CPP. Results indicate that even for full
      autoregulation, CBF is decreased during CPB. It is even lower for impaired
      autoregulation and hypertensive patients, demonstrating the strong impact of
      autoregulation on CBF. It is therefore imperative to include this mechanism into
      CFD studies. The presented model can help to improve CPB support conditions based
      on patient-specific autoregulation parameters.

PMID- 22882445
TI  - Medical responses following the Sendai quake (East Japan earthquake, march 11,
      2011).

PMID- 22882443
TI  - Miniaturization of mechanical circulatory support systems.
AB  - Heart failure (HF) is increasing worldwide and represents a major burden in terms
      of health care resources and costs. Despite advances in medical care, prognosis
      with HF remains poor, especially in advanced stages. The large patient population
      with advanced HF and the limited number of donor organs stimulated the
      development of mechanical circulatory support (MCS) devices as a bridge to
      transplant and for destination therapy. However, MCS devices require a major
      operative intervention, cardiopulmonary bypass, and blood component exposure,
      which have been associated with significant adverse event rates, and long
      recovery periods. Miniaturization of MCS devices and the development of an
      efficient and reliable transcutaneous energy transfer system may provide the
      vehicle to overcome these limitations and usher in a new clinical paradigm in
      heart failure therapy by enabling less invasive beating heart surgical procedures
      for implantation, reduce cost, and improve patient outcomes and quality of life.
      Further, it is anticipated that future ventricular assist device technology will
      allow for a much wider application of the therapy in the treatment of heart
      failure including its use for myocardial recovery and as a platform for support
      for cell therapy in addition to permanent long-term support.

PMID- 22882447
TI  - Ex situ cultivation affects genetic structure and diversity in arable plants.
AB  - Worldwide, botanical gardens cultivate around 80,000 taxa, corresponding to
      approximately one-quarter of all vascular plants. Most cultivated taxa are,
      however, held in a small number of collections, and mostly only in small
      populations. Lack of genetic exchange and stochastic processes in small
      populations make them susceptible to detrimental genetic effects, which should be
      most severe in annual species, as sowing cycles are often short. In order to
      assess whether ex situ cultivation affects genetic diversity of annuals, five
      annual arable species with similar breeding systems were assessed with 42 in situ
      populations being compared to 20 ex situ populations using a random amplified
      polymorphic DNA (RAPD) analysis approach. Population sizes tended to be lower
      under ex situ cultivation and levels of genetic diversity also tended to be lower
      in four of the five species, with differences being significant in only two. Ex
      situ populations showed incomplete representation of alleles found in the wild.
      The duration of cultivation did not indicate any effect on genetic diversity.
      This implies that cultivation strategies resulted in different genetic structures
      in the garden populations. Although not unequivocally pronounced, differences
      nonetheless imply that conservation strategies in the involved gardens may need
      improvement. One option is cold storage of seeds, a practice that is not
      currently followed in the studied ex situ collections. This may reflect that the
      respective gardens focus on displaying living plant populations.

PMID- 22882449
TI  - Poly(I:C) promotes the production of IL-17A by murine CD1d-driven invariant NKT
      cells in airway inflammation.
AB  - BACKGROUND: IL-17A is associated with different asthma phenotypes as virus
      associated or steroid-resistant asthma. Invariant natural killer T (iNKT) cells
      play an important role in the pathogenesis of asthma. The aim of the study was to
      evaluate the activity of polyinosinic-polycytidylic acid [poly(I:C)] on IL-17A
      production by CD1d-activated iNKT cells. METHODS: We analysed the in vitro effect
      of poly(I:C) on the release of IL-17A by spleen and lung CD1d-activated iNKT
      cells with alpha-galactosylceramide (alpha-GalCer). Its activity was also
      investigated in an alpha-GalCer-induced murine models, including lung
      inflammation. The inhibition of IL-17A by Toll-like receptor (TLR) 7 agonists in
      the same in vitro and in vivo models has been analysed. RESULTS: Poly(I:C)
      upregulated the in vitro IL-17A production by CD1d-activated NK1.1- CD4- iNKT
      subset, without modifying type 1 and type 2 cytokines. The two stimuli
      selectively upregulated IL-17A serum levels in vivo. Their intratracheal
      administration resulted in increased airway hyper-reactivity (AHR), neutrophilia
      in bronchoalveolar lavage and airway inflammation, which were inhibited by anti
      IL-17A antibody. Poly(I:C) effects were attributable to IL1beta and IL-23 release
      from dendritic cells, as showed by inhibition with neutralizing antibodies. TLR7
      agonists inhibited the IL-17A production by poly(I:C) plus alpha-GalCer in the
      same models. Such effect was associated with the increased production by DC of IL
      17A-inhibiting cytokines and the dampening of IL-1beta and IL-23. CONCLUSIONS:
      Synthetic dsRNA selectively expand a CD1d-driven IL-17A-producing iNKT cell
      subset, thus explaining the worsening of airway inflammation by some viral
      infections. TLR3- and TLR7-triggering viral sequences can exert variable and
      opposite effects on adaptive immune response.

PMID- 22882448
TI  - Epithelial mesenchymal transition traits in honey-driven keratinocyte wound
      healing: comparison among different honeys.
AB  - Honey has been used since ancient times for wound repair, but the subjacent
      mechanisms are almost unknown. We have tried to elucidate the modulatory role of
      honey in an in vitro model of HaCaT keratinocyte re-epithelialization by using
      acacia, buckwheat, and manuka honeys. Scratch wound and migration assays showed
      similar increases of re-epithelialization rates and chemoattractant effects in
      the presence of different types of honey (0.1%, v/v). However, the use of kinase
      and calcium inhibitors suggested the occurrence of different mechanisms. All
      honeys activated cyclin-dependent kinase 2, focal adhesion kinase, and rasGAP SH3
      binding protein 1. However, vasodilator-stimulated phosphoprotein, integrin
      beta3, cdc25C, and p42/44 mitogen activated protein kinase showed variable
      activation pattern. Re-epithelialization recapitulates traits of epithelial
      mesenchymal transition (EMT) and the induction of this process was evaluated by a
      polymerase chain reaction array, revealing marked differences among honeys.
      Manuka induced few significant changes in the expression of EMT-regulatory genes,
      while the other two honeys acted on a wider number of genes and partially showed
      a common profile of up- and down-regulation. In conclusion, our findings have
      shown that honey-driven wound repair goes through the activation of keratinocyte
      re-epithelialization, but the ability of inducing EMT varies sensibly among
      honeys, according to their botanical origin.

PMID- 22882450
TI  - Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ
      hybridization analysis.
AB  - We present a case of a 64-year-old man with refractory acute myeloid leukemia and
      trisomy 8 who developed leukemia cutis. Interphase fluorescence in situ
      hybridization (FISH) was performed on a paraffin-embedded skin section. FISH
      confirmed a population of cells with trisomy 8 in the blastic infiltrates
      involving the skin. This case illustrates a novel application of interphase FISH
      to confirm the diagnosis of leukemia cutis.

PMID- 22882451
TI  - Abiotic drivers and plant traits explain landscape-scale patterns in soil
      microbial communities.
AB  - The controls on aboveground community composition and diversity have been
      extensively studied, but our understanding of the drivers of belowground
      microbial communities is relatively lacking, despite their importance for
      ecosystem functioning. In this study, we fitted statistical models to explain
      landscape-scale variation in soil microbial community composition using data from
      180 sites covering a broad range of grassland types, soil and climatic conditions
      in England. We found that variation in soil microbial communities was explained
      by abiotic factors like climate, pH and soil properties. Biotic factors, namely
      community-weighted means (CWM) of plant functional traits, also explained
      variation in soil microbial communities. In particular, more bacterial-dominated
      microbial communities were associated with exploitative plant traits versus
      fungal-dominated communities with resource-conservative traits, showing that
      plant functional traits and soil microbial communities are closely related at the
      landscape scale.

PMID- 22882452
TI  - Scanning electron microscopic study for pore formation of the greater omentum of
      cats.
AB  - The greater omentum of the cats is said to have a lace-like structure. However,
      there are only a few descriptions on whether pores exist, and there are not many
      morphological studies on this meshwork. In this study, the greater omentum of the
      cats was observed at each age of development using a scanning electron
      microscope. The greater omentum of the cats immediately after birth was found to
      be continuous, and no pores were observed. Also, development of microvilli was
      observed in the mesothelial cells on the surface of the greater omentum. In young
      cats at 3 months of age, small pores were sporadically observed, and at the ages
      of 6-12 months, there were more and larger pores. It was estimated that the pores
      on the greater omentum are formed in the process of moving from the movement of
      organs, such as the stomach, intestines and diaphragm, and the presence of these
      pores enables the passage of ascites between the omental bursa, the greater
      omentum and the serosal cavity of the wall without flowing through the omental
      foramen.

PMID- 22882453
TI  - Prediction of long-term outcomes of catheter ablation of persistent atrial
      fibrillation by parameters of preablation DC cardioversion.
AB  - AIM: It has been demonstrated that atrial fibrillation (AF) frequently recurred
      after cardioversion (CV) using direct current (DC) or radiofrequency catheter
      ablation (RFCA) in patients with persistent (PeAF) or longstanding persistent AF
      (LPAF). We hypothesized that the atrial substrate impeding successful CV would
      also produce difficulty in catheter ablation, and therefore, the outcomes of RFCA
      for PeAF and LPAF could be predicted by the parameters determined at the time of
      DC CV. METHOD: From 2006 to 2009, 94 patients with PeAF and LPAF who had
      undergone elective DC CV before RFCA were studied. The parameters associated with
      DC CV, including number of shocks, cumulative energy adjusted, highest energy
      adjusted, with or without intravenous amiodarone use, and other clinical
      parameters were assessed. RESULT: Thirty-two out of the 94 patients (34%)
      experienced AF recurrence during the follow-up of 19.8 +/- 12.3 months after
      RFCA. The average time to recurrence of AF after RFCA was 9.2 +/- 3.2 months. Of
      the 62 patients, 29 patients (31%) remained sinus rhythm (SR) without
      antiarrhythmic drug (AAD). The patients who maintained SR had smaller body mass
      index (BMI) (P = 0.048), shorter duration of AF (P = 0.012), and lower prevalence
      of diabetes mellitus (P = 0.023) compared with patients in whom AF recurred.
      Total number of shocks, total energy, and highest shock energy during CV were
      lower (P < 0.001, P = 0.002, P = 0.048, respectively) in patients with SR during
      the follow-up. The outcome in patients who used amiodarone IV prior to CV,
      however, was not different from that in those who did not use amiodarone IV.
      CONCLUSION: DC energy parameters for successful CV before RFCA were useful to
      predict the long-term outcome after RFCA in patients with PeAF and LPAF. The
      presence of the atrial substrate making DC CV difficult might reflect atrial
      substrate that subsequently related to the recurrence of AF after RFCA in chronic
      AF. These DC energy parameters may be related to the chronicity or
      electroanatomical remodeling of AF.

PMID- 22882454
TI  - Increased infection risk postliver transplant without pretransplant dental
      treatment.
AB  - OBJECTIVE: Infections cause considerable morbidity after liver transplantation
      (LT). Acute liver failure is a rapidly progressing life-threatening condition
      where pretransplant dental evaluation is not always possible. We investigated how
      missing pretransplant dental treatment in acute or subacute liver failure
      correlates with post-transplant infectious complications. SUBJECTS AND METHODS:
      Medical and dental data came from hospital records and infection data from the
      Finnish LT registry. The follow-up was until February 2011. Of 51 patients (LT
      during 2000-2006), 16 had and 35 did not have dental treatment pretransplant.
      RESULTS: Univariate Cox regression analysis demonstrated a 2.46-fold (95% CI 1.06
      5.69) infection risk among the patients omitted from dental treatment. After
      adjustment for either pretransplant factors alone or both pre- and post
      transplant factors, the corresponding infection risk increased, respectively, to
      8.17-fold (95% CI 2.19-30.6) and 8.54-fold (95% CI 1.82-40.1). This increased
      risk involved a variety of bacterial, viral, and fungal infections of various
      sources both < 6 and > 6 months after transplantation. CONCLUSION: High risk of
      infections was noticed in acute liver failure patients without pretransplant
      dental treatment, but a more severe medical condition might have influenced the
      results. We encourage eradication of dental infection foci whenever clinical
      condition allows.

PMID- 22882455
TI  - A longitudinal study of survival in Belgian Shepherds with genetic epilepsy.
AB  - BACKGROUND: Belgian Shepherds have focal genetic epilepsy. The prevalence of
      epilepsy has been estimated as 9.5% in the breed and as 33% in the family
      investigated. Dogs with epilepsy might have an increased risk of premature death.
      OBJECTIVE/HYPOTHESIS: To investigate survival and selected risk factors for
      premature death in a Belgian Shepherd family with genetic epilepsy. ANIMALS: One
      hundred ninety-nine related Belgian Shepherds. METHODS: Longitudinal
      observational study, 2009-2011. Follow-up telephone interviews were all conducted
      using a structured questionnaire addressing epilepsy, including seizure history
      and phenomenology, possible remission, possible death, and cause of death.
      RESULTS: The life span of epileptic dogs was not significantly shortened by the
      presence of epilepsy (P = .87). Epilepsy was the predominant cause of death in
      the population (19/75 = 25%) and epilepsy-related deaths accounted for 70%
      (19/27) of all deaths in the group of dogs with epilepsy. Two probable sudden
      unexpected deaths related to epilepsy occurred in dogs with generalized seizures.
      Cluster seizures occurred in 33% (17/51) but did not significantly influence the
      life span of epileptic dogs. Dogs with epilepsy had an epilepsy remission
      proportion of 13.7%. CONCLUSION AND CLINICAL IMPORTANCE: The Belgian Shepherds
      investigated in the present study display a focal genetic epilepsy with an
      overall benign course. The life span was not significantly affected by the
      presence of epilepsy.

PMID- 22882456
TI  - Australian consumer perspectives on dialysis: first national census.
AB  - AIM: The percentage of people in Australia who undertake home dialysis has
      steadily decreased over the past 40 years and varies within Australia. Consumer
      factors related to this decline have not previously been determined. METHODS: A
      78-question survey was developed and piloted in 2008 and 2009. Survey forms were
      distributed to all adult routine dialysis patients in all Australian states and
      territories (except Northern Territory) between 2009 and 2010. Of 9223
      distributed surveys, 3250 were completed and returned. RESULTS: 49% of
      respondents indicated they had no choice in the type of dialysis and 48% had no
      choice in dialysis location. Respondents were twice as likely to receive
      information about haemodialysis (85%) than APD (39%) or CAPD (41%). The provision
      of education regarding home modalities differed significantly between states, and
      decreased with increasing patient age. Additional nursing support and
      reimbursement of expenses increased the proportion of those willing to commence
      dialysis at home, from 13% to 34%. State differences in the willingness to
      consider home dialysis, the degree of choice in dialysis location, the desire to
      change current dialysis type and/or location, and the provision of information
      about dialysis were identified. CONCLUSION: The delivery of pre-dialysis
      education is variable, and does not support all options of dialysis for all
      individuals. State variances indicate that local policy and health professional
      teams significantly influence the operation of dialysis programs.

PMID- 22882457
TI  - Adjuvant selection for vaccination against murine schistosomiasis.
AB  - Schistosoma mansoni cercariae penetrate mouse epidermis, detach the glycocalyx
      and transform into schistosomula, triggering innate immune responses by host
      keratinocytes and Langerhans cells. Schistosomula leave the dermis and enter
      blood capillaries, releasing excretory/secretory products (ESP), which induce
      readily detectable primary adaptive immunity responses, dominated by T helper
      (Th) 1 and 17 cytokines. Partial protection against murine schistosomiasis may be
      achieved using subunit antigens and Th1 cytokine-inducing adjuvants. Conversely,
      resistance to primary and/or secondary schistosomiasis in rats, mice and humans
      is associated with production of Th2 cytokines. Accordingly, we reasoned that
      effective vaccination against murine primary schistosomiasis might be achieved
      provided selection of an adjuvant capable of skewing the S. mansoni larval ESP
      mediated Th1/Th17 immune responses towards a Th2 profile. In an aim to select
      such an adjuvant, we administered the prototypical Th1 and Th2, respectively,
      C57BL/6 and BALB/c mice with polyinosinic-polycytidylic acid (Poly I/C),
      peptidoglycan (PGN), or thymic stromal lymphopoietin (TSLP) before exposure to S.
      mansoni cercariae. Serum antibody reactivity and ex vivo spleen cells (SC) immune
      responses to larval ESP, in a recombinant or multiple antigen peptide form, were
      assessed 1 week after infection. Injection with Poly I/C failed to increase
      interleukin (IL)-4 and led to elevated gamma interferon (IFN-gamma) levels
      released by unstimulated or ESP-stimulated SC. Treatment with PGN triggered
      hightened amounts of IL-4, IL-17 and IFN-gamma released by unstimulated or ESP
      stimulated C57BL/6 SC. In contrast, TSLP succeeded in directing the ESP-mediated
      immune responses towards a Th2-biased profile in prototypical Th1 and Th2 mice.

PMID- 22882459
TI  - Overview of pharmacoeconomic modelling methods.
AB  - In the current climate of burgeoning health care costs, pharmacoeconomics is
      becoming increasingly important, but knowledge about pharmacoeconomic methods is
      limited among most clinicians. This review provides an introduction to, and
      overview of, common methods used in pharmacoeconomic modelling: decision
      analysis, Markov modelling, discounting and uncertainty analyses via Monte Carlo
      simulation. It will conclude with a suggested approach to reading and appraising
      published pharmacoeconomic analyses.

PMID- 22882460
TI  - A novel mutation in exon 8 of C1 inhibitor (C1INH) gene leads to abolish its
      physiological stop codon in a large Chinese family with hereditary angioedema
      type I.
AB  - C1 inhibitor (C1INH) plays an important role in the classical pathway of the
      complement system. Mutations in C1INH gene cause quantitative or qualitative
      deficiencies in C1INH, which can lead to hereditary angioedema (HAE) type I or
      II. Here, we identified a novel frame-shift mutation c.1391-1445del55
      (p.v464fsx556) in exon 8 in a large Chinese family with HAE type I. This 55 base
      pairs deletion abolishes the original stop codon and introduces a new stop codon
      220 bp downstream of the original one, and leads to mutated C1INH protein
      prolonged from 500 to 556 amino acids. The levels of C4 and C1INH as well as
      C1INH activity in serum were significantly reduced in affected individuals. This
      is the first report of a novel mutation abolishing the physiological stop codon
      of C1INH gene in a large Chinese family with HAE type I.

PMID- 22882458
TI  - Genetic isolation within the malaria mosquito Anopheles melas.
AB  - Anopheles melas is a brackish water-breeding member of the Anopheles gambiae
      complex that is distributed along the coast of West Africa and is a major malaria
      vector within its range. Because little is known about the population structure
      of this species, we analysed 15 microsatellite markers and 1161 bp of mtDNA in 11
      A. melas populations collected throughout its range. Compared with its sibling
      species A. gambiae, A. melas populations have a high level of genetic
      differentiation between them, representing its patchy distribution due to its
      fragmented larval habitat that is associated with mangroves and salt marsh grass.
      Populations clustered into three distinct groups representing Western Africa,
      Southern Africa and Bioko Island populations that appear to be mostly isolated.
      Fixed differences in the mtDNA are present between all three clusters, and a
      Bayesian clustering analysis of the microsatellite data found no evidence for
      migration from mainland to Bioko Island populations, and little migration was
      evident between the Southern to the Western cluster. Surprisingly, mtDNA
      divergence between the three A. melas clusters is on par with levels of
      divergence between other species of the A. gambiae complex, and no support for
      monophyly was observed in a maximum-likelihood phylogenetic analysis. Finally, an
      approximate Bayesian analysis of microsatellite data indicates that Bioko Island
      A. melas populations were connected to the mainland populations in the past, but
      became isolated, presumably when sea levels rose after the last glaciation period
      (>=10 000-11 000 bp). This study has exposed species-level genetic divergence
      within A. melas and also has implications for control of this malaria vector.

PMID- 22882461
TI  - Multiple pathways for high voltage-activated ca(2+)  influx in anterior pituitary
      lactotrophs and somatotrophs.
AB  - The present study demonstrates that a significant proportion of high voltage
      activated (HVA) Ca(2+) influx in native rat anterior pituitary cells is carried
      through non-L-type Ca(2+) channels. Using whole-cell patch-clamp recordings and
      specific Ca(2+) channel toxin blockers, we show that approximately 35% of the HVA
      Ca(2+) influx in somatotrophs and lactotrophs is carried through Ca(v) 2.1, Ca(v)
      2.2 and Ca(v) 2.3 channels, and that somatotrophs and lactotrophs share similar
      proportions of these non-L-type Ca(2+) channels. Furthermore, experiments on
      mixed populations of native anterior pituitary cells revealed that the fraction
      of HVA Ca(2+) influx carried through these non-L-type Ca(2+) channels might even
      be higher (approximately 46%), suggesting that non-L-type channels exist in the
      majority of native anterior pituitary cells. Using western blotting, immunoblots
      for alpha(1C) , alpha(1D) , alpha(1A) , alpha(1B) and alpha(1E) Ca(2+) channel
      subunits were identified in native rat anterior pituitary cells. Additionally,
      using reverse transcriptase-polymerase chain reaction, cDNA transcripts for
      alpha(1C) , alpha(1D) , alpha(1A) and alpha(1B) Ca(2+) channel subunits were
      identified. Transcripts for alpha(1E) were nonspecific and transcripts for
      alpha(1S) were not detected at all (control). Taken together, these results
      clearly demonstrate the existence of multiple HVA Ca(2+) channels in the membrane
      of rat native anterior pituitary cells. Whether these channels are segregated
      among different membrane compartments was investigated further in flotation
      assays, demonstrating that Ca(v) 2.1, Ca(v) 1.2 and caveolin-1 were mostly
      localised in light fractions of Nycodenz gradients (i.e. in lipid raft domains).
      Ca(v) 1.3 channels were distributed among both light and heavy fractions of the
      gradients (i.e. among raft and nonraft domains), whereas Ca(v) 2.2 and Ca(v) 2.3
      channels were distributed mostly among nonraft domains. In summary, in the
      present study, we demonstrate multiple pathways for HVA Ca(2+) influx through L
      type and non-L-type Ca(2+) channels in the membrane of native anterior pituitary
      cells. The compartmentalisation of these channels among raft and nonraft membrane
      domains might be essential for their proper regulation by separate receptors and
      signalling pathways.

PMID- 22882462
TI  - Low-level laser therapy restores the oxidative stress balance in acute lung
      injury induced by gut ischemia and reperfusion.
AB  - It remains unknown if the oxidative stress can be regulated by low-level laser
      therapy (LLLT) in lung inflammation induced by intestinal reperfusion (i-I/R). A
      study was developed in which rats were irradiated (660 nm, 30 mW, 5.4 J) on the
      skin over the bronchus and euthanized 2 h after the initial of intestinal
      reperfusion. Lung edema and bronchoalveolar lavage fluid neutrophils were
      measured by the Evans blue extravasation and myeloperoxidase (MPO) activity
      respectively. Lung histology was used for analyzing the injury score. Reactive
      oxygen species (ROS) was measured by fluorescence. Both expression intercellular
      adhesion molecule 1 (ICAM-1) and peroxisome proliferator-activated receptor-y
      (PPARy) were measured by RT-PCR. The lung immunohistochemical localization of
      ICAM-1 was visualized as a brown stain. Both lung HSP70 and glutathione protein
      were evaluated by ELISA. LLLT reduced neatly the edema, neutrophils influx, MPO
      activity and ICAM-1 mRNA expression. LLLT also reduced the ROS formation and
      oppositely increased GSH concentration in lung from i-I/R groups. Both HSP70 and
      PPARy expression also were elevated after laser irradiation. Results indicate
      that laser effect in attenuating the acute lung inflammation is driven to restore
      the balance between the pro- and antioxidants mediators rising of PPARy
      expression and consequently the HSP70 production.

PMID- 22882463
TI  - Left colonic graft in esophageal reconstruction for caustic stricture: mortality
      and morbidity.
AB  - The adequacy of the blood supply to the left colon graft and its ability to
      transport food effectively from pharynx to stomach made it an esophageal
      substitute of choice, particularly in esophageal caustic stricture. From 1999 to
      2009, 60 patients underwent colon interposition for esophageal caustic stricture
      (n= 57) and cancer (n= 3). An isoperistaltic colonic graft based on the left
      colonic artery could be used in all of these patients. The substernal route was
      used exclusively, and upper thoracic inlet was opened when necessary. The
      isoperistaltic left colonic graft interposed by substernal route represents the
      surgical procedure of choice in all operations performed for esophageal
      substitution during the study period. The operative mortality rate was 3.3%. A
      cervical fistula occurred in 10 patients (16.6%) and cervical anastomotic
      stricture in five patients (8.3%). Dilation was required in all the stricture of
      the esophageal colonic anastomosis with good response. The isoperistaltic left
      colic transplant supplied by the left colic pedicle is an excellent long-term
      replacement organ for the esophageal caustic stenosis. When performed by
      experienced surgeons, the left isoperistaltic esophagocoloplasty is a
      satisfactory surgical method for esophageal reconstruction with acceptable early
      morbidity and good long-term functional results. 

PMID- 22882464
TI  - Rabeprazole 10 mg q.d.s. decreases 24-h intragastric acidity significantly more
      than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype.
AB  - BACKGROUND: Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs)
      cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using
      PPIs are required to sustain potent acid inhibition for the full 24 h in all
      patients with acid-related diseases. AIM: To evaluate acid inhibitory effects by
      different dosing times of a PPI at the same daily dosage, in a study involving 70
      rounds of pH monitoring. METHODS: Using pH monitoring, we evaluated the efficacy
      of different divided treatment regimens with the same total daily dose of
      rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35
      rounds) on day 7 or 8 of PPI dosing. RESULTS: In the study of divided treatment,
      the median pH (when administered once, twice or four times to achieve a daily
      dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively.
      When comparing the median pHs at the same CYP2C19 genotype among different dosing
      times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly
      higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing
      effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy:
      95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype. CONCLUSION: Four times
      daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including
      during the night-time, suggesting its potential usefulness as a regimen for
      patients who are refractory to standard once daily PPI treatment.

PMID- 22882465
TI  - Are single nucleotide polymorphisms in the oxytocin and vasopressin 1A/1B
      receptor genes likely candidates for variation in ejaculatory function?
AB  - What's known on the subject? and What does the study add? There is also evidence
      that the etiology of premature ejaculation is partially genetic. So far, all
      molecular genetic studies of premature ejaculation have focused on serotonergic
      and dopaminergic genes. Serotonergic and dopaminergic neurotransmission aside,
      studies on both animals and humans have shown that both oxytocin and vasopressin
      are also involved in ejaculatory function. The present study is, to our
      knowledge, the first to investigate effects of polymorphisms in oxytocin and
      vasopressin receptor genes on ejaculatory function. Although a large sample (1517
      men) was available for the present study, we could not detect any clear-cut
      effects of any gene variant on ejaculatory function. We detected a heterozygote
      effect of one polymorphism (rs75775) in the oxytocin receptor gene. Rare variants
      of the vasopressin receptor 1A gene may theoretically have a stronger impact on
      ejaculatory function, but would need a very large sample in order to be
      established. Based on our results, we conclude that the oxytocin and vasopressin
      receptor genes are unlikely targets for successful pharmacogenetic interventions.
      OBJECTIVES: * To investigate associations between single nucleotide polymorphisms
      (SNPs) linked to the oxytocin, and arginine vasopressin 1A and 1B receptor genes
      and ejaculatory function. * To investigate these associations in a large,
      population-based sample. PATIENTS AND METHODS: * In all, 1517 male twins and non
      twin brothers of twins aged 18-45 years (mean = 26.43; sd = 4.87) provided
      questionnaire data regarding ejaculatory function and relevant covariates and
      saliva samples for genotyping. * A Bayesian linear mixed-effects model, which
      appropriately controls for between-subjects dependence, was used to estimate
      genotype associations. * We corrected for multiple testing using a linkage
      disequilibrium correlation measure. RESULTS: * We found a heterozygote effect on
      one SNP in the oxytocin receptor gene (rs75775), so that individuals heterozygous
      for this SNP had significantly elevated risk for premature ejaculation symptoms
      compared with carriers of either homozygote. * Several SNPs in the arginine
      vasopressin receptor genes had rare or very rare genotypes. This study may be
      underpowered to detect potential effects of rare genotypic variants in arginine
      vasopressin receptor genes. CONCLUSIONS: * Our results regarding the oxytocin
      receptor polymorphisms support previous studies that indicate a complex
      relationship between oxytocin and ejaculatory function. * Oxytocin receptor genes
      are, for example, unlikely suitable targets for pharmacogenetic intervention
      studies. * Rare variants in arginine vasopressin receptor genes may have
      significant effects on premature ejaculation, but would need larger sample sizes
      or case-control designs to be detected.

PMID- 22882467
TI  - Prevalence and risk factors of atopic diseases in German children and
      adolescents.
AB  - BACKGROUND: Atopic diseases became an important health problem in affluent
      Western societies. METHODS: To study the prevalence and factors associated with
      the risk of atopic diseases in Germany, data from the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS) were analysed (n =
      17,450). Standardized, computer-assisted personal interviews with parents and
      parent-administered questionnaires provided physician diagnoses of allergic
      rhinoconjunctivitis, atopic dermatitis and asthma as well as data on demographic
      characteristics, migration background, birth order, age at the beginning of
      nursery, atopic diseases of parents, parents' smoking status, parents'
      occupation, breastfeeding and living environment. RESULTS: The life-time
      prevalence of atopic dermatitis was 13.2% (95% confidence limit: 12.5-13.9%),
      10.7% (10.1-11.3%) for allergic rhinoconjunctivitis and 4.7% (4.3-5.1%) for
      asthma. At least one atopic disease in parents was the strongest factor
      associated with atopic diseases in the offspring, with a prevalence ratio of up
      to 2.6. High and middle socio-economic status (prevalence ratio, 95% confidence
      limit: 1.28, 1.12-1.46; 1.15, 1.01-1.32) were associated with the risk of atopic
      dermatitis, whereas a two-sided background of migration reduced the risk (0.76,
      0.65-0.88). Factors that reduced the risk of allergic rhinoconjunctivitis were
      parents working as self-employed farmers (0.48, 0.30-0.76) and older siblings
      (0.80, 0.71-0.89), whereas the beginning of nursery school at older age was
      associated with an increased risk in children who were cared for outside the
      family before school age (1.05, 1.00-1.10). Living in mould-infested rooms (1.64,
      1.23-2.19), an urban living environment (1.20, 1.02-1.42) and a smoking mother
      and/or father (1.20, 1.02-1.40) were associated with the risk of asthma.
      CONCLUSIONS: Our results are in line with the so-called 'hygiene hypothesis',
      which emphasizes the role of environmental factors in addition to a genetic
      predisposition in the development of atopic diseases. Research on factors
      associated with atopic diseases can facilitate decisions on preventive
      strategies. Further studies are needed to explore trends in prevalence and risk
      factors for atopic diseases.

PMID- 22882466
TI  - Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a
      DNA damage response.
AB  - In senescent cells, a DNA damage response drives not only irreversible loss of
      replicative capacity but also production and secretion of reactive oxygen species
      (ROS) and bioactive peptides including pro-inflammatory cytokines. This makes
      senescent cells a potential cause of tissue functional decline in aging. To our
      knowledge, we show here for the first time evidence suggesting that DNA damage
      induces a senescence-like state in mature postmitotic neurons in vivo. About 40
      80% of Purkinje neurons and 20-40% of cortical, hippocampal and peripheral
      neurons in the myenteric plexus from old C57Bl/6 mice showed severe DNA damage,
      activated p38MAPkinase, high ROS production and oxidative damage, interleukin IL
      6 production, heterochromatinization and senescence-associated beta-galactosidase
      activity. Frequencies of these senescence-like neurons increased with age. Short
      term caloric restriction tended to decrease frequencies of positive cells. The
      phenotype was aggravated in brains of late-generation TERC-/- mice with
      dysfunctional telomeres. It was fully rescued by loss of p21(CDKN1A) function in
      late-generation TERC-/-CDKN1A-/- mice, indicating p21 as the necessary signal
      transducer between DNA damage response and senescence-like phenotype in neurons,
      as in senescing fibroblasts and other proliferation-competent cells. We conclude
      that a senescence-like phenotype is possibly not restricted to proliferation
      competent cells. Rather, dysfunctional telomeres and/or accumulated DNA damage
      can induce a DNA damage response leading to a phenotype in postmitotic neurons
      that resembles cell senescence in multiple features. Senescence-like neurons
      might be a source of oxidative and inflammatory stress and a contributor to brain
      aging.

PMID- 22882468
TI  - Radicular pain in post lumbar surgery syndrome: the significance of
      transforaminal injection of steroids.
AB  - OBJECTIVE: The objective of the study was to see if transforaminal injection of
      steroids might be an effective treatment for persistent radicular pain after disc
      surgery. DESIGN: The study was designed as a retrospective practice audit
      covering a time period of 2 years. SETTING: The study was set in a single spine
      center in which all patients underwent lumbar disc surgery, postoperative follow
      up, and subsequent treatment. INTERVENTIONS: Patients with postsurgical radicular
      pain were treated with a transforaminal injection of a steroid. The effect was
      evaluated in terms of pain reduction, duration of pain relief, and in relation to
      a recurrent disc herniation in postperative magnetic resonance imaging. RESULTS:
      Of 479 patients who underwent microsurgical lumbar disc surgery, 69 had
      persistent radicular pain. Transforaminal injection of steroid achieved pain
      reduction of at least 50% in 26.8% of these patients. The success rate was higher
      (43%) in patients without a recurrent disc herniation. CONCLUSIONS:
      Transforaminal injection of steroid appears to be effective in only a minority of
      patients with radicular pain persisting after disc surgery, but is more often
      effective in patients without recurrent disc herniation.

PMID- 22882469
TI  - Malignant transformation of a putative eyelid papilloma to squamous cell
      carcinoma in a dog.
AB  - A 6-year-old female spayed Chihuahua was presented for the evaluation of
      generalized pigmented cutaneous masses, one of which was present on the lower
      right eyelid. The dog was not on immunosuppressive medications and did not have
      historical or laboratory evidence of underlying endocrine disease, including
      hypothyroidism and hyperadrenocorticism. Histopathology, immunohistochemistry,
      and polymerase chain reaction of a cutaneous biopsy from the left antebrachium
      containing representative lesions confirmed viral papillomatosis. Additionally,
      histopathology of the antebrachial mass revealed regions of epithelial dysplasia
      suggestive of possible early transformation to malignancy. Over the course of 5
      months, the mass on the right lower eyelid progressed to encompass and efface the
      majority of the eyelid margin. Additionally, the eyelid tumor had changed from an
      ovoid, brown pigmented mass to an irregular, flesh-colored mass. At the dog's
      last recheck examination, a corneal ulcer had developed beneath the irregular
      dorsal margin of the tumor. Histopathology of the eyelid mass was consistent with
      squamous cell carcinoma (SCC) and was positive for the presence of papillomavirus
      using polymerase chain reaction. This report describes the transformation of a
      putative viral eyelid papilloma into a malignant SCC in an adult dog. 

PMID- 22882470
TI  - Effects of platelet-rich plasma (PRP) on the healing of Achilles tendons of rats.
AB  - Platelet-rich plasma (PRP) contains growth factors involved in the tissular
      healing process. The aim of the study was to determine if an injection of PRP
      could improve the healing of sectioned Achilles tendons of rats. After surgery,
      rats received an injection of PRP (n = 60) or a physiological solution (n = 60)
      in situ. After 5, 15, and 30 days, 20 rats of both groups were euthanized and 15
      collected tendons were submitted to a biomechanical test using cryo-jaws before
      performing transcriptomic analyses. Histological and biochemical analyses were
      performed on the five remaining tendons in each group. Tendons in the PRP group
      were more resistant to rupture at 15 and 30 days. The mechanical stress was
      significantly increased in tendons of the PRP group at day 30. Histological
      analysis showed a precocious deposition of fibrillar collagen at day 5 confirmed
      by a biochemical measurement. The expression of tenomodulin was significantly
      higher at day 5. The messenger RNA levels of type III collagen, matrix
      metalloproteinases 2, 3, and 9, were similar in the two groups at all time
      points, whereas type I collagen was significantly increased at day 30 in the PRP
      group. In conclusion, an injection of PRP in sectioned rat Achilles tendon
      influences the early phase of tendon healing and results in an ultimately
      stronger mechanical resistance.

PMID- 22882471
TI  - Increased number of circulating endothelial cells (CECs) in patients with
      psoriasis--preliminary report.
AB  - BACKGROUND: Numerous studies have demonstrated increased cardiovascular risk in
      psoriasis. Circulating endothelial cells (CECs) have been proposed as a new
      marker of endothelial dysfunction that plays an important role in pathogenesis of
      atherosclerosis. OBJECTIVE: The aim of this study was to compare the number of
      CECs in psoriatic patients to a control group and to analyze possible
      correlations between the numbers of CECs and the plasma levels of classical
      markers of endothelial dysfunction, such as: sICAM-1, sE-selectin and von
      Willebrand factor (vWF). METHODS: The number of CECs, identified as CD146 + /
      CD45- cells, were determined in peripheral blood with using flow cytometry in
      psoriatic patients (n = 63) and controls (n = 31). The plasma levels of: sICAM-1,
      sE-selectin, vWF were measured with ELISA. The severity of psoriasis was assessed
      with PASI. RESULTS: The number of CECs was significantly increased in psoriatic
      patients compared with controls (P < 0.00001) and positively correlated with
      disease severity (R = 0.360; P = 0.0037). The levels of sICAM-1, sE-selectin and
      vWF were significantly elevated in psoriatic patients (P < 0.00001; P < 0.00001;
      P = 0.00072, respectively). The number of CECs was significantly, positively
      correlated with the levels of sICAM-1 (R = 0.393; P = 0.0014) and vWF (R = 0.314;
      P = 0.012) in psoriatic patients. The levels of sICAM-1 and sE-selectin were
      positively correlated with disease severity (R = 0.356; P = 0.0041 and R = 0.407;
      P = 0.0009, respectively). CONCLUSION: The increased number of CECs that
      correlates with disease severity and plasma levels of sICAM-1 and vWF may
      indicate endothelial dysfunction or injury in patients with psoriasis.

PMID- 22882472
TI  - Effects of neuromuscular electrical stimulation and aerobic exercise training on
      arterial stiffness and autonomic functions in patients with chronic heart
      failure.
AB  - Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in
      clinical practice as a rehabilitation (RHB) method in patients with chronic heart
      failure (CHF); however, the role of NMES on the reduction of arterial stiffness
      and autonomic disbalance in these patients has not yet been studied. Sixty-one
      patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31
      [4.2]%, New York Heart Association II-III) were randomly assigned into two
      groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks
      of bicycle ET (3 * 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of
      NMES of quadriceps and calf muscles (frequency 10 Hz, mode "20 s on-20 s off,"
      intensity 60 mA), 2 * 60 min/day. Noninvasive assessment of arterial stiffness
      was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate
      variability (HRV) and .VO(2peak) were evaluated before and after RHB program.
      Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P <
      0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P < 0.013), increased high frequency
      (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency
      (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P < 0.001).
      Changes of HRV parameters in group NMES were not significant; however, a marked
      tendency to autonomic stabilization was present. Both types of RHB led also to
      significant increase of .VO(2peak) (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P
      < 0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P < 0.001). ET or NMES has
      been shown to improve significantly arterial stiffness and to stabilize autonomic
      balance.

PMID- 22882473
TI  - Maintenance of storage properties of pediatric aliquots of apheresis platelets in
      fluoroethylene propylene containers.
AB  - BACKGROUND: Platelet (PLT) aliquots for pediatric use have been shown to retain
      in vitro properties when stored in gas-impermeable syringes for up to 6 hours. As
      an alternative, PLT aliquots can be stored for longer periods in containers used
      for storage of whole blood-derived PLTs. These containers are not available
      separate from whole blood collection sets and PLT volumes less than 35 mL either
      have not been evaluated or may be unsuitable for PLT storage. Gas-permeable
      fluoroethylene propylene (FEP) containers have been used in the storage of cell
      therapy preparations and are available in multiple sizes as single containers but
      have not been evaluated for PLT storage. STUDY DESIGN AND METHODS: A single
      apheresis unit was divided on Day 3 into small aliquots with volume ranging from
      20 to 60 mL, transferred using a sterile connection device, and stored for an
      additional 2 days either in CLX (control) or in FEP containers. PLT storage
      properties of PLTs stored in FEP containers were compared to those stored in CLX
      containers. Standard PLT in vitro assays were performed (n =6). RESULTS: PLT
      storage properties were either similar to those of CLX containers or differed by
      less than 20% excepting carbon dioxide levels, which varied less than 60%.
      CONCLUSION: Pediatric PLT aliquots of 20, 30, and 60mL transferred on Day 3 into
      FEP cell culture containers adequately maintain PLT properties for an additional
      2days of storage.

PMID- 22882474
TI  - Managing hepatitis B virus carriers with systemic chemotherapy or biologic
      therapy in the outpatient clinic.
AB  - AIM:   The number of outpatients receiving systemic chemotherapy in Japan has
      recently increased. We retrospectively examined whether hepatitis B virus (HBV)
      carriers were safely treated and managed with systemic chemotherapy or biologic
      agents as outpatients at our oncology center. METHODS:   A total of 40 115
      consecutive infusion chemotherapy or biologic therapies were administrated to
      2754 outpatients in the Chemotherapy and Oncology Center at Osaka University
      Hospital from December 2003 to March 2011. We first studied the prevalence of
      outpatients with hepatitis B surface antigen (HBsAg), and then retrospectively
      evaluated a database to determine the frequencies of testing for other HBV
      related markers and the incidence of developing hepatitis or HBV reactivation in
      patients positive for HBsAg. As a control for comparison, we also examined these
      same factors in patients with hepatitis C virus antibody (anti-HCV). RESULTS:  
      The majority of physicians at our hospital screened for HBsAg (95%) and anti-HCV
      (94%) prior to administrating chemotherapy. Of the 2754 outpatients, 46 (1.7%)
      were positive for HBsAg and 90 (3.3%) were positive for anti-HCV. Fifteen
      patients that were HBsAg positive were treated with lamivudine or entecavir prior
      to chemotherapy. None of the patients with HBsAg taking a prophylactic antiviral
      developed hepatitis, and only one breast cancer patient without prophylactic
      antiviral treatment (1/31 [3.2%]) developed hepatitis due to HBV reactivation.
      CONCLUSION:   HBV reactivation occurred in outpatients without prophylactic
      antiviral treatment, but the incidence was relatively low.

PMID- 22882475
TI  - Clear cell adenocarcinoma arising from endometriosis in abdominal wall cesarean
      section scar: a case report and review of the literature.
AB  - Malignancy arising in association with endometriosis is a rare but well
      documented phenomenon that was first described in the literature as early as
      1925. Cutaneous endometriosis with subsequent malignant transformation is even
      more uncommon, and high clinical suspicion is required for diagnosis. The
      clinical differential diagnosis of these lesions includes a wide variety of
      entities, ranging from benign cysts to malignancies such as melanoma. We report a
      case of clear cell adenocarcinoma arising from endometriosis in a cesarean
      section scar in a 47-year-old woman, and we complete a review of the literature
      regarding this unusual entity.

PMID- 22882476
TI  - Distribution and in situ abundance of sulfate-reducing bacteria in diverse marine
      hydrocarbon seep sediments.
AB  - Marine gas and hydrocarbon seeps are hot spots of sulfate reduction which is
      fuelled by methane, other short-chain alkanes or a complex mixture of
      hydrocarbons. In this study, we investigated the global distribution and
      abundance of sulfate-reducing bacteria (SRB) in eight gas and hydrocarbon seeps
      by catalysed reporter deposition fluorescence in situ hybridization (CARD-FISH).
      The majority of Deltaproteobacteria were assigned to specific SRB groups, i.e. 83
      +/- 14% at gas seeps and 61 +/- 35% at hydrocarbon seeps, indicating that the
      probe set used was sufficient for classification of marine SRB. Statistical
      analysis showed that SRB abundance and distribution were significantly influenced
      by habitat type and sediment depth. Members of the Desulfosarcina/Desulfococcus
      (DSS) clade strongly dominated all sites. Our data indicated the presence of many
      diverse and highly specialized DSS species of low abundance rather than a single
      abundant subgroup. In addition, SEEP-SRB2, an uncultured deep-branching
      deltaproteobacterial group, was ubiquitously found in high abundances at all
      sites. SEEP-SRB2 members occurred either in a novel association with
      methanotrophic archaea in shell-type ANME-2/SEEP-SRB2 consortia, in association
      with ANME-1 archaea in Black Sea microbial mats or as single cells. Two other
      uncultured groups, SEEP-SRB3 and SEEP-SRB4, were preferentially detected in
      surface sediments from mud volcanoes.

PMID- 22882477
TI  - An examination of hardiness throughout the sport-injury process: a qualitative
      follow-up study.
AB  - OBJECTIVES: This qualitative follow-up study aimed to enhance the
      interpretability and meaningfulness of the findings that emerged from a
      quantitative study that explored the effect of hardiness on the prediction of,
      and response to, sport injury (i.e., Wadey, Evans, Hanton, & Neil, 2012). DESIGN:
      Using theory-based and maximum-variation sampling to contextualize and provide an
      in-depth understanding of the previous findings, the participants comprised a
      purposeful sample of 10 athletes from the quantitative study (M age = 21.7; SD=
      1.06). METHODS: Data were derived through semi-structured interviews, and
      analysed and displayed using composite sequence analysis (Miles & Huberman,
      1994). RESULTS: The findings extended Wadey et al.'s (2012) study by identifying
      the perceived mechanisms by which athletes high and low in hardiness exacerbated
      or attenuated the impact of pre-injury negative major life events (i.e., a
      significant predictor of sport injury) and post-injury responses. Specifically,
      the findings demonstrate that athletes high in hardiness possessed a refined
      repertoire of problem- and emotion-focused coping strategies that they used pre-
      and post-injury. Those athletes low in hardiness used avoidance coping strategies
      that had long-term negative implications. CONCLUSIONS: These findings have
      important implications for the structure, timing, and content of hardiness
      interventions that aim to reduce rates of injury occurrence and expedite injured
      athletes' return to competitive sport.

PMID- 22882478
TI  - Comparison of the location of slow conduction velocity in cavotricuspid-dependent
      atrial flutter in patients with and without prior atriotomy: different
      arrhythmogenic basis and clinical implications for placement of atriotomy.
AB  - Slow Zone in CTI-Dependent Flutter After Atriotomy. INTRODUCTION: Earlier studies
      have shown that the slow conduction zone in patients with cavotriscuspid (CTI)
      dependent atrial flutter without prior surgery (NS-AFL) is the CTI. However, the
      location of this slow zone in patients with CTI-dependent flutter and a prior
      atriotomy has not been formally studied. Identification of the slow zone in
      patients with prior atriotomy and CTI-dependent atrial flutter (PA-AFL) and
      comparison with NS-AFL may have important clinical implications. METHODS AND
      RESULTS: Seventeen consecutive patients with PA-AFL and 17 consecutive patients
      with NS-AFL were included. Conduction velocity (CV) was measured using 3
      dimensional mapping in 3 areas around the TVA. These regions were defined as the
      CTI area from lateral inferior vena cava orifice to coronary sinus ostium (region
      I), mid- to upper-septum (S), and free wall (F). In region F, the CV was much
      slower in PA-AFL than in NS-AFL patients (0.43 +/- 0.13 vs 0.76 +/- 0.26 m/s, P <
      0.01). However, region I was slower in NS-AFL than PA-AFL (0.57 +/- 0.18 m/s vs
      0.84 +/- 0.24 m/s, P < 0.01). In all PA-AFL patients, the slow zone was in region
      F. But in most (11/17) NS-AFL patients the slow zone was in region I. There was
      no significant difference in CV in region S between the 2 groups. CONCLUSIONS:
      Unlike NS-AFL, CTI in PA-AFL displays relatively normal conduction but the slow
      zone is on the free wall. This arrhythmogenecity of atriotomy may perhaps be
      avoided if the incisional line were altered to extend to the TV. (J Cardiovasc
      Electrophysiol, Vol. 23, pp. 988-995, September 2012).

PMID- 22882479
TI  - Suicidal ideation and sexual orientation in college students: the roles of
      perceived burdensomeness, thwarted belongingness, and perceived rejection due to
      sexual orientation.
AB  - A theoretical model in which perceived burdensomeness and thwarted belongingness
      were hypothesized to account for the association between sexual orientation and
      suicidal ideation among college students was tested. Among 198 college students
      (mean age 21.28 years), gay, lesbian, and bisexual students (n = 50) reported
      significantly higher levels of perceived burdensomeness and suicidal ideation
      than heterosexual students. The relationship between sexual orientation and
      suicidal ideation was partially accounted for by perceived burdensomeness, but
      not thwarted belongingness. This indirect effect was stronger at higher levels of
      perceived or anticipated rejection due to one's sexual orientation. Implications
      for intervention and prevention science are discussed.

PMID- 22882480
TI  - Association among quality of  life, dental caries treatment and  intraoral
      distribution in  12-year-old South Brazilian  schoolchildren.
AB  - OBJECTIVES: To assess the association between dental caries treatment, intraoral
      distribution and oral health-related quality of life (OHRQoL) of 12-year-old
      South Brazilian schoolchildren. METHODS: This crosssectional survey used a
      multistage probability sampling strategy to select a representative sample of
      schoolchildren from Porto Alegre, southern Brazil. Data were collected from
      September 2009 to December 2010, and 1528 of 1837 eligible schoolchildren
      attending public and private schools participated. Clinical examination was
      conducted to assess dental caries experience (DMFT). OHRQoL was assessed by a
      self-reported 16-item Child Perception Questionnaire (CPQ11-14). Parents/legal
      guardians answered questions on socio-economic status. Survey negative binomial
      regression models were used to assess the association between CPQ11-14 scores and
      caries treatment status (treated/untreated) and intraoral distribution
      (anterior/posterior). Estimates were controlled for gender and socioeconomic
      status. RESULTS: Compared to schoolchildren without treatment needs, individuals
      with treated caries presented an improved OHRQoL (overall CPQ11 -14, adjusted RR
      = 0.90, 95%CI = 0.85-0.96; functional limitations, adjusted RR = 0.86, 95%CI =
      0.75-0.99; emotional well-being, adjusted RR = 0.89, 95% CI = 0.80-0.99), whereas
      those with untreated caries presented a poorer OHRQoL (oral symptoms, adjusted RR
      = 1.06, 95%CI = 1.02-1.10; emotional well-being, adjusted RR = 1.09, 95%CI = 1.01
      1.20). Individuals with caries in anterior teeth experienced greater negative
      impact on oral symptoms (adjusted RR = 1.11, 95%CI = 1.05-1.18) and social well
      being (adjusted RR = 1.30; 95% CI = 1.14-1.47) domains than caries-free students.
      CONCLUSIONS: Treated caries was positively associated with OHRQoL; untreated
      caries and caries affecting anterior teeth were negatively associated with OHRQoL
      of 12-year-old Brazilian schoolchildren.

PMID- 22882481
TI  - Significant enrichment of Y-bearing chromosome human spermatozoa using a modified
      centrifugation technique.
AB  - The effective separation of X- and Y-bearing chromosome spermatozoa has been a
      topic of major attraction to a number of scientific disciplines. Approaches have
      typically been based upon either the kinetic or the physical characteristics of
      spermatozoa. Much of the information available to date has either suggested
      conflicting evidence between different approaches or a lack of repeatability,
      while other robust and reproducible techniques require expensive equipment and
      are being questioned with relation to their safety in clinical applications. This
      study describes a safe and efficient method for the successful enrichment of the
      Y-bearing chromosome spermatozoa cells from their X counterparts in the human
      male using a simple approach based on centrifugation. Five donor candidates with
      normal semen profiles and proven fertility were recruited. In total, 20 semen
      specimens were processed using conventional swim-up. During each attempt, half of
      the swim-up product was subjected to the enrichment technique and the other half
      served as control. Parameters important for successfully skewing sex ratios
      included the relative centrifugal force, the duration of centrifugal separation
      and the number of centrifugation rounds. Assessment of samples following the
      separation technique was effected by a three-colour-labelled fluorescent in situ
      hybridization. More than 1000 spermatozoa for each donor specimen were assessed
      for the presence of an X or Y chromosome. The enrichment technique produced a
      significantly higher (p < 0.001) overall frequency of 85.5% for the Y-bearing
      chromosome spermatozoa in the experimental group (3606 X-bearing/21, 209 Y
      bearing) compared with a frequency of 50.1% in the control group (11,801 X
      bearing/11,269 Y-bearing), where there was no statistically significant
      difference in the number of either X- or Y-chromosome-bearing spermatozoa. In
      conclusion, successful skewing of human Y-bearing chromosome spermatozoa can be
      reproducibly achieved by the use of simple swim-up followed by a meticulous
      centrifugation protocol.

PMID- 22882482
TI  - Expression of aquaporin3 in human neoplastic tissues.
AB  - AIMS: Aquaporin3 (AQP3) is distributed widely in mammalian tissues and plays an
      important role in fluid homeostasis. The aim of this study was to investigate the
      pattern of expression of AQP3 in a variety of human neoplastic tissues and to
      explore its diagnostic implications. METHODS AND RESULTS: We studied 798
      neoplastic tissues using immunohistochemistry with anti-AQP3 antibody. We
      demonstrated a high positive frequency of AQP3 immunoreactivity in pituitary
      adenomas, salivary gland tumours, thymic tumours, adenocarcinoma of the lung and
      prostate, squamous cell carcinomas of the skin, oesophagus and uterine cervix,
      apocrine carcinoma of the breast, germinal cell tumours of the ovary and testis
      and urothelial carcinoma of the bladder. None of the sarcomas or central nervous
      system tumours showed AQP3 immunoreactivity. Most tumours with a high frequency
      of AQP3 positivity had corresponding or surrounding normal cells that also
      expressed AQP3. AQP3 was not a specific marker for benign or malignant epithelial
      neoplasms. CONCLUSION: AQP3 protein is expressed in a variety of epithelial
      tumours limiting its use as a diagnostic marker. Furthermore, AQP3 expression in
      tumour cells reflected the expression status of AQP3 in the corresponding normal
      cells. Our data suggest that water metabolism through AQP3 is maintained during
      neoplastic transformation in most human tissues.

PMID- 22882484
TI  - Tyrosine kinase inhibitor special issue.

PMID- 22882483
TI  - Involvement of the ubiquitin-proteasome system in the stabilization of cell-cell
      contacts in human keratinocytes.
AB  - Desmosomes are highly organized intercellular junctions composed of a number of
      interacting proteins that provide mechanical integrity to epithelial tissues.
      Mutations in genes encoding desmosomal proteins, including desmoplakin (DP), are
      associated with human hereditary diseases affecting skin integrity. The detailed
      mechanism of desmosome assembly remains, despite many efforts, incompletely
      understood. Recently, the ubiquitin-proteasome system (UPS) has been suggested to
      be an important regulatory system for the proper intracellular trafficking of
      proteins. Here, we provide evidence for a calcium-independent, but UPS-dependent,
      stabilization of cell-cell contacts in human keratinocytes, which might be
      mediated by the maintenance of DP at desmosomes.

PMID- 22882485
TI  - Receptor tyrosine kinase inhibitors: molecularly targeted drugs for veterinary
      cancer therapy.
AB  - Tyrosine kinases (TKs) are key mediators of signalling pathways in cells. Located
      at the surface of the cell, within the cytoplasm or in the nucleous, TKs have
      been showed to be involved in regulation of normal cellular processes and also
      play an important role in the development, progression and spread of several
      types of cancer. Seventy percent of TK's are Receptor Tyrosine Kinases and these
      have become key targets for cancer therapy. This short synopsis is intended to
      give the reader an introduction to this area of targeted therapy for cancer as a
      prelude to this special edition of Veterinary and Comparative Oncology.

PMID- 22882486
TI  - European consensus document on mast cell tumours in dogs and cats.
AB  - In preparing this document the Authors aimed to pool current information on
      canine and feline mast cell disease. The information was gathered from
      international studies and a emphasis was placed on material and opinion with a
      strong evidence base. We intend it to form the basis of our understanding in this
      disease at the current time and we anticipate that it will be particularly useful
      for the general practitioner. It should be emphasized that the authors are
      presenting this work from a European perspective.

PMID- 22882487
TI  - Utilization of wireless pH monitoring technologies: a summary of the proceedings
      from the esophageal diagnostic working group.
AB  - Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms
      alone are often not enough, and thus, objective testing is often required. GERD
      is a manifestation of pathologic levels of reflux into the esophagus of acidic,
      nonacidic, and/or bilious gastric content. However, in our current evidence-based
      knowledge approach, we only have reasonable outcome data in regards to acid
      reflux, as this particular type of refluxate predictably causes symptoms and
      mucosal damage, which improves with medical or surgical therapy. While there are
      data suggesting that nonacid reflux may be responsible for ongoing symptoms
      despite acid suppression in some patients, outcome data about this issue are
      limited. Therefore, this working group believes that it is essential to confirm
      the presence of acid reflux in patients with 'refractory' GERD symptoms or
      extraesophageal symptoms thought to be caused by gastroesophageal reflux before
      an escalation of antireflux therapy is considered. If patients do not have
      pathologic acid reflux off antisecretory therapy, they are unlikely to have
      clinically significant nonacid or bile reflux. Patients who do not have
      pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring
      then: (i) could attempt to discontinue antisecretory medications like proton pump
      inhibitors and H2-receptor antagonists (which are expensive and which carry risks
      - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of
      their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic
      esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and
      (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for
      assessment of non-GERD causes of their extraesophageal symptoms. 

PMID- 22882488
TI  - Quantifying acute changes in volume and nutritional status during haemodialysis
      using bioimpedance analysis.
AB  - AIM: To determine the precision of multi-frequency bioimpedance analysis (MFBIA)
      in quantifying acute changes in volume and nutritional status during
      haemodialysis, in patients with end-stage renal disease (ESRD). METHODS: Using
      whole-body MFBIA, we prospectively studied changes in total body water (TBW),
      extracellular volume (ECV), intracellular volume (ICV), lean body mass (LBM),
      body cell mass (BCM) and fat mass (FM), pre- and post-haemodialysis and tested
      the agreement of volume changes with corresponding acute weight change and
      ultrafiltration volume (UF) using Bland-Altman analysis. RESULTS: Forty-four
      prevalent and 17 incident haemodialysis patients were studied (median age 55
      years, 56% males). MFBIA-derived TBW, ECV, ICV, LBM and BCM were significantly
      reduced after haemodialysis (P < 0.001), but FM remained constant. TBW change
      estimated weight change with mean bias of -0.52 L, with 56/61 (91.8%) data points
      within limits of agreement (-2.74 L, 1.69 L). TBW change estimated UF with mean
      bias of -0.62 L, with 55/61 (90.2%) data points within limits of agreement (-2.68
      L, 1.43 L). ECV change underestimated weight change and UF with mean bias of 
      1.17 L and -1.27 L respectively. Similarly, ICV change underestimated both
      clinical measures with corresponding mean bias of -1.34 L and -1.44 L. Comparing
      incidents versus prevalent haemodialysis patients, TBW change estimated weight
      change with smaller mean bias (-0.10 L vs-0.69 L, respectively) and narrower
      limits of agreement. CONCLUSION: Multi-frequency bioimpedance analysis-derived
      TBW chan e has the best agreement with acute clinical volume change during
      haemodialysis compared to ECV or ICV change alone, but overall degree of
      precision remains poor. Nutritional assessment using LBM and BCM measurements is
      significantly confounded by hydration status.

PMID- 22882489
TI  - Angle closure in the developing world: what does the future hold?

PMID- 22882490
TI  - Laser photocoagulation for diabetic macular oedema in the era of anti-vascular
      endothelial growth factor therapy: is there a role?

PMID- 22882492
TI  - Transitory activation of the central and ovarian norepinephrine systems during
      cold stress-induced polycystic ovary in rats.
AB  - Cold stress-induced ovarian sympathetic activation is associated with the
      development of ovarian cysts in rats. Although we have hypothesised that
      polycystic ovary (PCO) features induced by cold stress, as prevented by lesion of
      the noradrenergic nucleus locus coeruleus (LC), were a result of the increased
      activity of the ovarian norepinephrine (NE) system, this was not evident after 8
      weeks of stress. In the present study, we investigated the temporal changes in LC
      and ovarian NE activities and steroid secretion in rats exposed to single (SS) or
      repeated (RS) cold stress. SS and 4 week (4W)-RS but not 8 week (8W)-RS increased
      c-Fos expression in the LC and ovarian NE release. Plasma oestradiol,
      testosterone and progesterone levels tended to increase in 4W-RS and were
      elevated in 8W-RS rats, which displayed PCO morphology. beta-adrenergic receptor
      agonist increased steroid hormone release from the ovary of unstressed (US) but
      not from 8W-RS rats. To determine whether increased activity of noradrenergic
      system during the initial 4 weeks of RS would be sufficient to promote PCO, rats
      were exposed to 4 weeks of cold stress and kept in ambient temperature for the
      next 4 weeks (4W-RS/4W-US). Accordingly, PCO morphology, increased steroid
      secretion and decreased ovulation rate were found in 4W-RS/4W-US rats,
      strengthening the hypothesis that the initial increase in NE release triggers the
      development of PCO. The correlated activity of LC neurones and ovarian
      noradrenergic terminals and the induction of PCO in 4W-RS/4W-US rats provide
      functional evidence for a major role of NE in disrupting follicular development
      and causing the long-lasting endocrine abnormalities found in stress-induced PCO.

PMID- 22882493
TI  - Acute effects of exposure to vapors of 3-methyl-1-butanol in humans.
AB  - The secondary alcohol 3-methyl-1-butanol (3MB, isoamyl alcohol) is used, for
      example, as a solvent in a variety of applications and as a fragrance ingredient.
      It is also one of the microbial volatile organic compounds (MVOCs) found in
      indoor air. There are little data on acute effects. The aim of the study was to
      assess the acute effects of 3MB in humans. Thirty healthy volunteers (16 men and
      14 women) were exposed in random order to 1 mg/m(3) 3MB or clean air for 2 h at
      controlled conditions. Ratings with visual analogue scales revealed slightly
      increased perceptions of eye irritation (P = 0.048, Wilcoxon) and smell (P <
      0.0001) compared with control exposure. The other ratings were not significantly
      affected (irritation in nose and throat, dyspnea, headache, fatigue, dizziness,
      nausea, and intoxication). No significant exposure-related effects were found in
      blinking frequency, tear film break-up time, vital staining of the eye, nasal
      lavage biomarkers, lung function, and nasal swelling. In conclusion, this study
      suggests that 3MB is not a causative factor for health effects in damp and moldy
      buildings. PRACTICAL IMPLICATIONS: 3-Methyl-1-butanol (3MB) is one of the most
      commonly reported MVOCs in damp and moldy buildings and in occupational settings
      related to agriculture and composting. Our study revealed no irritation effects
      at 1 mg/m3, a concentration higher than typically found in damp and moldy
      buildings. Our study thus suggests that 3MB is not a causative factor for health
      effects in damp and moldy buildings.

PMID- 22882494
TI  - Identification of marneral synthase, which is critical for growth and development
      in Arabidopsis.
AB  - Plants produce structurally diverse triterpenoids, which are important for their
      life and survival. Most triterpenoids and sterols share a common biosynthetic
      intermediate, 2,3-oxidosqualene (OS), which is cyclized by 2,3-oxidosqualene
      cyclase (OSC). To investigate the role of an OSC, marneral synthase 1 (MRN1), in
      planta, we characterized a Arabidopsis mrn1 knock-out mutant displaying round
      shaped leaves, late flowering, and delayed embryogenesis. Reduced growth of mrn1
      was caused by inhibition of cell expansion and elongation. Marnerol, a reduced
      form of marneral, was detected in Arabidopsis overexpressing MRN1, but not in the
      wild type or mrn1. Alterations in the levels of sterols and triterpenols and
      defects in membrane integrity and permeability were observed in the mrn1. In
      addition, GUS expression, under the control of the MRN1 gene promoter, was
      specifically detected in shoot and root apical meristems, which are responsible
      for primary growth, and the mRNA expression of Arabidopsis clade II OSCs was
      preferentially observed in roots and siliques containing developing seeds. The
      eGFP:MRN1 was localized to the endoplasmic reticulum in tobacco protoplasts.
      Taken together, this report provides evidence that the unusual triterpenoid
      pathway via marneral synthase is important for the growth and development of
      Arabidopsis.

PMID- 22882495
TI  - Photodynamic mechanisms induced by a combination of hypericin and a chlorin based
      photosensitizer in head and neck squamous cell carcinoma cells.
AB  - The aim of this study was to elucidate photodynamic therapy (PDT) effects
      mediated by hypericin and a liposomal meso-tetrahydroxyphenyl chlorin (mTHPC)
      derivative, with focus on their 1:1 mixture, on head and neck squamous cell
      carcinoma cell lines. Absorption, excitation and photobleaching were monitored
      using fluorescence spectrometry, showing the same spectral patterns for the
      mixture as measured for single photosensitizers. In the mixture mTHPC showed a
      prolonged photo-stability. Singlet oxygen yield for light-activated mTHPC was
      Phi(Delta) = 0.66, for hypericin Phi(Delta) = 0.25 and for the mixture Phi(Delta)
      = ~0.4. A linear increase of singlet oxygen yield for mTHPC and the mixture was
      found, whereas hypericin achieved saturation after 35 min. Reactive oxygen
      species fluorescence was only visible after hypericin and mixture-induced PDT.
      Cell viability was also more affected with these two treatment options under the
      selected conditions. Examination of death pathways showed that hypericin-mediated
      cell death was apoptotic, with mTHPC necrotic and the 1:1 mixture showed features
      of both. Changes in gene expression after PDT indicated strong up-regulation of
      selected heat-shock proteins. The application of photosensitizer mixtures with
      the features of reduced dark toxicity and combined apoptotic and necrotic cell
      death may be beneficial in clinical PDT. This will be the focus of our future
      investigations.

PMID- 22882496
TI  - The regulation of ATP release from the urothelium by adenosine and
      transepithelial potential.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Stretch of the
      urothelium, as occurs during bladder filling, is associated with a release of ATP
      that is postulated to act as a sensory neurotransmitter. The regulation of ATP
      release is poorly understood and in particular if there is a feedback mechanism
      provided by ATP itself. Adenosine, a breakdown product of ATP, is a potent
      inhibitor of stretch-induced ATP release, acting through and A1 receptor;
      endogenous levels are about 0.6MUM. Data are consistent with ATP release relying
      on the rise of intracellular Ca2+. Transepithelial potential also controls ATP
      release, also acting via an A1 receptor-dependent pathway. OBJECTIVES: To test
      the hypothesis that distension-induced ATP release from the bladder urothelium is
      regulated by adenosine as well as changes to transurothelial potential (TEP). To
      examine the role of changes to intracellular [Ca(2+) ] in ATP release. MATERIALS
      AND METHODS: Rabbit urothelium/suburothelium membranes were used in an Ussing
      chamber system. Distension was induced by fluid removal from the chamber bathing
      the serosal (basolateral) membrane face. The TEP and short-circuit current were
      measured. ATP was measured in samples aspirated from the serosal chamber by a
      luciferin-luciferase assay. Intracellular [Ca(2+) ] was measured in isolated
      urothelial cells using the fluorochrome Fura-2. All experiments were performed at
      37 degrees C. RESULTS: Distension-induced ATP release was decreased by adenosine
      (1-10 MUm) and enhanced by adenosine deaminase and A1- (but not A2-) receptor
      antagonists. Distension-induced ATP release was reduced by 2-APB, nifedipine and
      capsazepine; capsaicin induced ATP release in the absence of distension. ATP and
      capsaicin, but not adenosine, generated intracellular Ca(2+) transients;
      adenosine did not affect the ATP-generated Ca(2+) transient. ATP release was
      dependent on a finite transepithelial potential. Changes to TEP, in the absence
      of distension, generated ATP release that was in turn reduced by adenosine.
      CONCLUSION: Adenosine exerts a powerful negative feedback control of ATP release
      from the urothelium via A1 receptor activation. Distension-induced ATP release
      may be mediated by a rise of the intracellular [Ca(2+) ]. Modulation of
      distension-induced ATP release by adenosine and TEP may have a common pathway.

PMID- 22882497
TI  - Birds as reservoirs for Borrelia burgdorferi s.l. in Western Europe: circulation
      of B. turdi and other genospecies in bird-tick cycles in Portugal.
AB  - Birds are important in the ecology of Borrelia burgdorferi sensu lato (s.l.)
      because they are important hosts for vector tick immature stages and are known
      reservoirs for some Borrelia genospecies. The aim of our study was to assess the
      role of common passerine bird species as reservoirs for B. burgdorferi s.l. in
      Western Europe. We surveyed birds in enzootic areas in Portugal, where no
      information is available for birds as reservoirs for this aetiologic agent and
      where B. lusitaniae, for which few reservoirs have been identified, is the
      dominant genospecies. Twenty-three birds (2.9%), including Turdus merula, T.
      philomelos, Parus major and Fringilla coelebs harboured infected ticks, but only
      Turdus sp. harboured infected tick larvae. In one study area, although B.
      lusitaniae was dominant in questing Ixodes ricinus, no ticks feeding on birds
      were infected with this genospecies, and B. valaisiana was the dominant
      genospecies in I. ricinus larvae feeding on birds. In the other area ticks
      collected from birds were mainly I. frontalis which were infected with B. turdi.
      Two skin biopsies (4.2%) from two T. merula were positive, one for B. valaisiana
      and the other for B. turdi. This is the first report for B. turdi in Western
      Europe.

PMID- 22882498
TI  - Conditional knockout of heparin-binding epidermal growth factor-like growth
      factor in the liver accelerates carbon tetrachloride-induced liver injury in
      mice.
AB  - AIM:   We previously demonstrated that heparin-binding epidermal growth factor
      like growth factor (HB-EGF) is induced in response to several liver injuries.
      Because the HB-EGF knockout (KO) mice die in utero or immediately after birth due
      to cardiac defects, the loss of function study in vivo is limited. Here, we
      generated liver-specific HB-EGF conditional knockout mice using the interferon
      inducible Mx-1 promoter driven cre recombinase transgene and investigated its
      role during acute liver injury. METHODS:   We induced acute liver injury by a
      single i.p. injection of carbon tetrachloride (CCl4 ) in HB-EGF KO mice and wild
      type mice and liver damage was assessed by biochemical and immunohistochemical
      analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular
      mechanism of HB-EGF-dependent anti-apoptosis and wound-healing process of the
      liver in vitro. RESULTS:   HB-EGF KO mice exhibited a significant increase of
      alanine aminotransferase level and also showed a significant increase in the
      number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase
      dUTP nick end labeling staining at 24 h after CCl4 injection. We also
      demonstrated that HB-EGF treatment inhibited tumor necrosis factor-alpha-induced
      apoptosis of AML12 mouse hepatocytes and promoted the wound-healing response of
      these cells. CONCLUSION:   This study showed that HB-EGF plays a protective role
      during acute liver injury.

PMID- 22882499
TI  - Adaptation of the dermal collagen structure of human skin and scar tissue in
      response to stretch: an experimental study.
AB  - Surgeons are often faced with large defects that are difficult to close.
      Stretching adjacent skin can facilitate wound closure. In clinical practice,
      intraoperative stretching is performed in a cyclical or continuous fashion.
      However, exact mechanisms of tissue adaptation to stretch remain unclear.
      Therefore, we investigated collagen and elastin orientation and morphology of
      stretched and nonstretched healthy skin and scars. Tissue samples were stretched,
      fixed in stretched-out position, and processed for histology. Objective methods
      were used to quantify the collagen orientation index (COI), bundle thickness, and
      bundle spacing. Also sections were analyzed for elastin orientation and quantity.
      Significantly more parallel aligned collagen bundles were found after cyclical
      (COI = 0.57) and continuous stretch (COI = 0.57) compared with nonstretched skin
      (COI = 0.40). Similarly, more parallel aligned elastin was found after stretch.
      Also, significantly thicker collagen bundles and more bundle spacing were found
      after stretch. For stretched scars, significantly more parallel aligned collagen
      was found (COI = 0.61) compared with nonstretched scars (COI = 0.49). In
      conclusion, both elastin and collagen realign in a parallel fashion in response
      to stretch. For healthy skin, thicker bundles and more space between the bundles
      were found. Rapid changes in extension, alignment, and collagen morphology appear
      to be the underlying mechanisms of adaptation to stretching.

PMID- 22882500
TI  - Autologous peripheral blood hematopoietic cell transplantation in dogs with B
      cell lymphoma.
AB  - BACKGROUND: Peripheral blood CD34+ hematopoietic cell transplantation (PBHCT) is
      commonly used to treat human patients with relapsed non-Hodgkin diffuse, large B
      cell lymphoma with cure rates approaching 50%. OBJECTIVE: To determine the safety
      and feasibility of performing PBHCT to treat canine B-cell lymphoma (LSA)
      patients in a clinical academic setting. ANIMALS: Twenty-four client-owned dogs
      diagnosed with B-cell LSA. METHODS: After high-dose cyclophosphamide and rhG
      colony-stimulating factor treatment, peripheral blood mononuclear cells were
      collected using cell separator machines. The harvested cells then were infused
      after a 10 Gy dose of total body irradiation (TBI). Post-irradiation adverse
      effects were managed symptomatically and dogs were discharged upon evidence of
      engraftment. RESULTS: More than 2 * 10(6) CD34+ cells/kg were harvested in 23/24
      dogs. Preapheresis peripheral blood monocyte count was correlated with the number
      of CD34+ cells/kg harvested. Twenty-one of 24 (87.5%) dogs engrafted
      appropriately, whereas 2 dogs (8.3%) died in the hospital. One (5%) dog exhibited
      delayed engraftment and died 45 days after PBHCT. One dog developed presumed TBI
      induced pulmonary fibrosis approximately 8 months after PBHCT. The median disease
      free interval and overall survival (OS) of all dogs from the time of PBHCT was
      271 and 463 days, respectively. Five of 15 (33%) dogs transplanted before they
      relapsed remain in clinical remission for their disease at a median OS of 524
      days (range, 361-665 days). CONCLUSIONS AND CLINICAL IMPORTANCE: In most cases,
      PBHCT led to complete hematologic reconstitution. Therefore, PBHCT may be
      considered as a treatment option for dogs with B-cell lymphoma.

PMID- 22882501
TI  - Management of castration-resistant prostate cancer: a call to urologists.

PMID- 22882502
TI  - A systematic review and meta-analysis of the effects of fluoride toothpastes on
      the prevention of dental caries in the primary dentition of preschool children.
AB  - OBJECTIVES: To assess the effects of fluoride (F) toothpastes on the prevention
      of dental caries in the primary dentition of preschool children. STUDY DESIGN:
      Systematic review and meta-analysis. METHODS: A search for randomized or quasi
      randomized clinical trials was carried out, without idiom restraints, in six
      electronic databases, registers of ongoing trials, meeting abstracts, dentistry
      journals and reference lists of potentially eligible studies. The search yielded
      1932 records and 159 full-text articles were independently read by two examiners.
      Data regarding characteristics of participants, interventions, outcomes, length
      of follow-up and potential of bias were independently extracted by two examiners
      on the basis of predetermined criteria. Any disagreement was solved by consensus
      after consulting a third examiner. Pooled prevented fractions (PF) and relative
      risks (RR) were estimated separately for studies testing low F toothpastes (<600
      ppm) and those testing standard F toothpastes (1000-1500 ppm). RESULTS: Eight
      clinical trials fulfilled the inclusion criteria and most of them compared F
      toothpastes associated with oral health education against no intervention. When
      standard F toothpastes were compared to placebo or no intervention, significant
      caries reduction at surface (PF = 31%; 95% CI 18-43; 2644 participants in five
      studies), tooth (PF = 16%; 95% CI 8-25; 2555 participants in one study) and
      individual (RR = 0.86; 95% CI 0.81-0.93; 2806 participants in two studies) level
      were observed. Low F toothpastes were effective only at surface level (PF = 40%;
      95% CI 5-75; 561 participants in two studies). CONCLUSION: Standard F toothpastes
      are effective in reducing dental caries in the primary teeth of preschool
      children and thus their use should be recommended to this age group.

PMID- 22882503
TI  - Reading outside the task fraternity.

PMID- 22882504
TI  - Unmasking the predicament of cultural voyeurism: a postcolonial analysis of
      international nursing placements.
AB  - The growing interest in international nursing placements cannot be left
      unnoticed. After 11 years into this twenty-first century, violations of human
      rights and freedom of speech, environmental disasters, and armed conflicts still
      create dire living conditions for men and women around the world. Nurses have an
      ethical duty to address issues of social justice and global health as a means to
      fulfil nursing's social mandate. However, international placements raise some
      concerns. Drawing on the works of postcolonial theorists in nursing and social
      sciences, we examine the risk of replicating colonialist practices and discourses
      of health in international clinical placements. Referring to Bakhtin's notions of
      dialogism and unfinalizability, we envision a culturally safe nursing practice
      arising from dialogical encounters between the Self as an Other and with the
      Other as an Other. We suggest that exploring the intricacies of cultural and race
      relations in everyday nursing practice are the premises upon which nurses can
      understand the broader historic, racial, gendered, political and economic
      contexts of global health issues. Finally, we make suggestions for developing
      culturally safe learning opportunities at the international level without
      minimizing the impact of dialogical cultural encounters occurring at the local
      and community levels.

PMID- 22882505
TI  - Nursing and competencies - a natural fit: the politics of skill /competency
      formation in nursing.
AB  - The last two decades have seen a significant restructuring of work across
      Australia and other industrialised economies, a critical part of which has been
      the appearance of competency based education and assessment. The competency
      movement is about creating a more flexible and mobile labour force to increase
      productivity and it does so by redefining work as a set of transferable or 'soft'
      generic skills that is transportable and is the possession of the individual.
      This article sought to develop an analysis of competency based clinical
      assessment of nursing students across a bachelor of nursing degree course. This
      involved an examination of a total of 406 clinical assessment tools that covered
      the years 1992-2009 and the three years of a bachelor degree. Data analysis
      generated three analytical findings: the existence of a hierarchy of competencies
      that prioritises soft skills over intellectual and technical skills; the
      appearance of skills as personal qualities or individual attributes; and the
      absence of context in assessment. The article argues that the convergence in
      nursing of soft skills and the professionalisation project reform has seen the
      former give legitimacy to the enduring invisibility and devaluation of nursing
      work.

PMID- 22882506
TI  - 'In a way, you have to pull the patient out of that state ...': the competency of
      ventilator weaning.
AB  - The introduction of the weaning protocol has reduced weaning time and improved
      results in patients. However, the evidence is inconsistent. This may reflect that
      the use of a protocol should not exclude individual considerations and clinical
      judgement. However, the significant aspects of the context and the competency
      important in the nurse-patient relationship in weaning have not yet been
      sufficiently described. This study aimed at exploring these aspects of weaning.
      Qualitative data from six in-depth interviews and field observations of three
      experienced intensive care nurses in weaning situations were analysed through
      systematic text condensation within a hermeneutic-phenomenological approach.
      Competency appeared to be based on thorough knowledge of physiology and
      ventilator skills, but also on knowing the patient, helping the nurse connect the
      meaningless to the meaningful for the patient. Behaving competently involves a
      continuous dialogue with the situation, observation of the patient's body
      language and symptoms over a period of time and the ability to see the
      interrelationships of all these elements. Competency in ventilator weaning may
      thus be linked to personal qualifications, while it is simultaneously dependent
      on a professional community that both confirms and acknowledges this competency.

PMID- 22882507
TI  - Patients' statements and experiences concerning receiving mechanical ventilation:
      a prospective video-recorded study.
AB  - Prospective studies using video-recordings of patients during mechanical
      ventilator treatment (MVT) while conscious have not previously been published.
      The aim was to describe patients' statements, communication and facial
      expressions during a video-recorded interview while undergoing MVT. Content
      analysis and hermeneutics inspired by the philosophy of Gadamer were used. The
      patients experienced almost constant difficulties in breathing and lost their
      voice. The most common types of communication techniques patients used were
      nodding or shaking the head. Their expressions were interpreted as stiffened
      facial expression, tense body position and feelings of sadness and sorrow.
      Nursing care for patients' conscious during MVT is challenging as it creates new
      demands regarding the content of the care provided. In caring for patients
      undergoing MVT while conscious, establishing a caring relationship, making
      patients feel safe and helping them to communicate seem to be most important for
      alleviating discomfort and instilling hope.

PMID- 22882508
TI  - We cannot staff for 'what ifs': the social organization of rural nurses'
      safeguarding work.
AB  - Rural nurses play an important role in the provision of maternity care for
      Canadian women. This care is an important part of how rural nurses safeguard the
      patients who receive care in small rural hospitals. This study utilized
      institutional ethnography as an approach for describing rural nursing work and
      for exploring how nurses' work experiences are socially organized. Rural nurses
      advocated for safe healthcare environments by ensuring that skilled nurses were
      available for every shift, day and night, at their local hospital. Rural nurses
      noted that this work was particularly difficult for the provision of maternity
      care. This article explores two threads or cues to institutional organization
      that were identified in our interviews and observations; namely staffing and
      safety standards, and the need for flexibility in staffing in small rural
      hospitals. Rural nurses' concerns about ensuring that skilled nurses are
      available in small rural hospitals do not enter into current management
      discourses that focus on efficiency and cost savings or find a home within
      current discourses of patient safety 'competencies'.

PMID- 22882509
TI  - Spanish nursing under Franco: reinvention, modernization and repression (1956
      1976).
AB  - This article examines Spanish nursing during a critical 20-year period (1956-76)
      when, under the dictatorial government of General Franco, nursing became the
      target of a modernization strategy. In the national standardized system of state
      run schools, the previously distinct nursing and midwifery programmes were merged
      into a new training programme which created the single professional denomination
      of ATS-Ayudante Tecnico Sanitario (Technical Sanitary Assistant). Under the
      leadership of medicine, and with the blessing of the Catholic Church and the
      Seccion Femenina (Women's Section of the Falangist Party), nursing was positioned
      as feminized and subordinate to medicine, a predominantly male profession in mid
      twentieth century Spain. This article discusses this crucial phase of Spanish
      nursing history by focusing on one influential historical document (published in
      1956), Professional Moral Orientation for the Sanitary Technical Assistants, a
      nursing textbook on professional morals for first-year nursing students written
      by Rosamaria Miranda, a Catholic nun and a trained nurse. Our analysis reveals
      that gender-related and technical discourses concerning disciplinary and pastoral
      power relations presented in this textbook legitimate the core beliefs of
      Franquism put forward by the politically powerful women's branch of the ruling
      Falangist Party in mid-twentieth century Spain.

PMID- 22882511
TI  - A temporary pacemaker initiates, then obscures, ventricular fibrillation.

PMID- 22882510
TI  - Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood
      donors and incidence and residual risk of transfusion transmission of hepatitis C
      virus.
AB  - BACKGROUND: We evaluate the current prevalence of serologic markers for hepatitis
      B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV
      incidence and residual transfusion-transmitted risk at three large Brazilian
      blood centers. STUDY DESIGN AND METHODS: Data on whole blood and platelet
      donations were collected from January through December 2007, analyzed by center;
      donor type; age; sex; donation status; and serologic results for hepatitis B
      surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and
      anti-HCV. HBV and HCV prevalence rates were calculated for all first-time
      donations. HCV incidence was derived including interdonation intervals that
      preceded first repeat donations given during the study, and HCV residual risk was
      estimated for transfusions derived from repeat donors. RESULTS: There were
      307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti-HBc
      reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191
      per 100,000 donations. There were significant associations between older age and
      hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence
      interval, 0.77-7.03) per 100,000 person-years, and residual risk of HCV window
      phase infections was estimated at 5.0 per million units transfused. CONCLUSION:
      Improvement in donor selection, socioeconomic conditions, and preventive
      measures, implemented over time, may have helped to decrease prevalence of HBV
      and HCV, relative to previous reports. Incidence and residual risk of HCV are
      also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood
      donors should help guide improved recruitment procedures, donor selection,
      laboratory screening, and counseling strategies.

PMID- 22882512
TI  - Using the Short Physical Performance Battery to screen for frailty in young-old
      adults with distinct socioeconomic conditions.
AB  - AIM: To analyze the Short Physical Performance Battery's (SPPB) ability in
      screening for frailty in community-dwelling young elderly from cities with
      distinct socioeconomic conditions. METHODS: Elderly (65-74 years-of-age) from
      Canada (Saint Bruno; n = 60) and Brazil (Santa Cruz; n = 64) were evaluated with
      the SPPB to assess physical performance. Frailty was defined as the presence of
      >= 3 of the following criteria: weight loss, exhaustion, weakness, mobility
      limitation and low physical activity. Linear regression and receiver operating
      characteristics analyses were carried out. RESULTS: The SPPB correlated with
      frailty (R(2) = 0.33), with better results for Saint Bruno. A cut-off of 9 in the
      SPPB had good sensitivity (92%) and specificity (80%) in discriminating frail
      from non-frail in Saint Bruno (area under the curve [AUC] = 0.81), but showed
      fair results in Santa Cruz (AUC = 0.61, sensitivity = 81% and specificity = 52%).
      CONCLUSIONS: The SPPB better discriminated frailty in elderly with higher
      socioeconomic conditions (Saint Bruno).

PMID- 22882513
TI  - Membrane transport of several ions during peritoneal dialysis: mathematical
      modeling.
AB  - Peritoneal dialysis utilizes a complex mass exchange device created by natural
      permselective membranes of the visceral and abdominal muscle tissues. In
      mathematical modeling of solute transport during peritoneal dialysis, each solute
      is typically considered as a neutral, independent particle. However, such
      mathematical models cannot predict transport parameters for small ions.
      Therefore, the impact of the electrostatic interactions between ions on the
      estimated transport parameters needs to be investigated. In this study, transport
      of sodium, chloride, and a third ion through a permselective membrane with
      characteristics of the peritoneal transport barrier was described using two
      models: a model with the Nernst-Planck (NP) equations for a set of interacting
      ions and a model with combined diffusive and convective transport of each ion
      separately (DC). Transport parameters for the NP model were calculated using the
      pore theory, while the parameters for the DC model were estimated by fitting the
      model to the predictions from the NP model. Solute concentration profiles in the
      membrane obtained by computer simulations based on these two models were similar,
      whereas the transport parameters (diffusive mass transport parameters and sieving
      coefficients) were generally different. The presence of the third ion could
      substantially modify the values of diffusive mass parameter for sodium and
      chloride ions estimated using the DC model compared with those predicted by NP.
      The extent of this modification depended on the molecular mass and concentration
      of the third ion, and the rate of volumetric flow. Closed formulas for the
      transport parameters of the DC model in terms of the NP model parameters, ion
      concentration profiles in the membrane, and volumetric flow across the membrane
      were derived. Their reliable approximations, which include only boundary ion
      concentrations instead of spatial intramembrane concentration profiles, were
      formulated. The precision of this approximation was demonstrated by numerical
      simulations of the investigated three-ion system. Our modeling demonstrated that
      the fitted transport parameters depend not only on ion molecular weight but also
      on the characteristics and concentration of all other ions in the fluid as well
      as on the fluid flow rate through the membrane. Therefore, theoretical
      predictions of ion transport parameters need to take into account multi-ionic
      character of dialysis and body fluids. The transport parameters estimated using
      the DC model for one ion may vary with the ionic composition, ion concentrations
      in the fluids, and volumetric flow and may not reflect the theoretical
      description of diffusive and convective characteristics of single ion.

PMID- 22882514
TI  - Motivations for self-injury, affect, and impulsivity: a comparison of individuals
      with current self-injury to individuals with a history of self-injury.
AB  - Individuals who report nonsuicidal self-injury (NSSI) are characterized by the
      tendency to act rashly while experiencing distress (negative urgency), the
      tendency to act without thinking, and endorsement of both social and affect
      regulation motives for the behavior. However, very little research has identified
      characteristics that distinguish current self-injurers from those with a history
      of the behavior. The purpose of this study was to compare individuals with
      current self-injury to a history of self-injury on impulsivity-related
      personality traits, motives for self-injury, and distress. Among a sample of 429
      undergraduates, 120 reported self-injury. Among these 120 individuals, 33
      endorsed self-injury within the past month, with a mean frequency of 4.77 acts of
      NSSI. Within the self-injury group, current self-injurers reported higher
      endorsement of affect regulation motives for NSSI, and higher levels of current
      negative affect than individuals with a history of self-injury. There were no
      differences between current and former self-injurers on measures of impulsivity,
      endorsement of social motives for NSSI, or positive affect. We propose that
      individuals who use NSSI to regulate negative affect may be more likely to
      repeatedly engage in this behavior over time.

PMID- 22882515
TI  - Selective resection of dorsal nerves of penis for premature ejaculation.
AB  - Premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions.
      Selective resection of the dorsal nerve (SRDN) of penis has recently been used
      for the treatment of PE and has shown some efficacy. To further clarify the
      efficacy and safety of SRDN on PE, we performed a preliminary, randomized,
      placebo-controlled clinical observational study. Persons with the complaints of
      rapid ejaculation, asking for circumcision because of redundant foreskin,
      intravaginal ejaculation latency time (IELT) within 2 min, not responding to
      antidepressant medication or disliking oral medication were randomly enrolled in
      two groups. From April 2007 to August 2010, a total of 101 eligible persons were
      enrolled, 40 of them received SRDN which dorsal nerves of the penis were
      selectively resected, and those (n = 61) enrolled in the control group were
      circumcised only. IELT and the Brief Male Sexual Function Inventory (BMSFI)
      questionnaire were implemented pre- and post-operatively for the evaluation of
      the effect and safety of the surgery. There are no statistically significant
      differences in the baseline data including mean ages, mean IELTs, perceived
      control abilities and the BMSFI mean scores between the two groups. With regard
      to the post-operative data of the surgery, both IELTs and perceived control
      abilities were significantly increased after SRDN (1.1 +/- 0.9 min vs. 3.8 +/-
      3.1 min for pre- and post-operative IELT, respectively, p < 0.01),whereas the
      post-operative results were not significantly improved for the control group (1.2
      +/- 0.7 min vs. 1.5 +/- 1.1 min, p > 0.05). Also, there were no statistically
      significant differences both in BMSFI composite and subscale scores between the
      two groups after surgery. Hence, we conclude that SRDN is effective in delaying
      ejaculation and improving ejaculatory control, whereas erectile function is not
      affected. The results imply that SRDN may be an alternative method for the
      treatment of PE for some patients.

PMID- 22882516
TI  - Conditioned media obtained from human outer root sheath follicular keratinocyte
      culture activates signalling pathways that contribute to maintenance of hair
      inducing capacity and increases trichogenicity of cultured dermal cells.
AB  - Findings from recent studies have demonstrated that hair-inducing capacity
      (trichogenicity) of cultured dermal cells can be maintained by addition of
      conditioned media obtained from culture of epidermal keratinocytes. In this
      study, we investigated the question of whether treatment with human follicular
      keratinocyte-conditioned media (FKCM) can result in activation of signalling
      pathways that contribute to trichogenicity and increase the trichogenicity of
      cultured dermal cells. Through conduct of hair reconstitution assays, we observed
      that treatment of cells with FKCM resulted in induction of a greater number of
      hair follicles, compared with control cells. Treatment of dermal cells with FKCM
      resulted in the activation of BMP and beta-catenin signalling pathways. In
      addition, higher levels of IGFBP-7, IL-8, OPG and uPA were observed in FKCM.
      Altogether, our data suggest that a patient's own FKCM would be ideal for
      expansion of the patient's own follicular dermal cells for cell therapy for
      treatment of hair loss.

PMID- 22882517
TI  - Salivary duct carcinomas can be classified into luminal androgen receptor
      positive, HER2 and basal-like phenotypes.
AB  - AIMS: The aim of this study was to devise a molecular classification for salivary
      duct carcinomas (SDCs) based on the similarities between SDCs and breast
      carcinomas and on characteristics of the microarray-based gene expression
      profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty
      two pure salivary duct carcinomas, 35 of which contained an in-situ component as
      defined by histological review and/or immunohistochemical analysis, were stained
      with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen
      receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth
      factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours
      were classified into HER2, luminal androgen receptor-positive, basal-like,
      luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%,
      9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like,
      indeterminate and luminal phenotype, respectively. The in-situ and invasive
      components displayed the same molecular subtype in all but one case. CONCLUSION:
      Salivary duct carcinomas can be classified into molecular subgroups approximately
      equivalent to those in the breast. We also report on the existence of a subgroup
      of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype.
      Understanding the phenotypic complexity of SDCs may help to expedite the
      identification of novel therapeutic targets for these aggressive tumours.

PMID- 22882518
TI  - Maintaining professionalism in today's business environment: ethical challenges
      for the pain medicine specialist.
AB  - OBJECTIVE: There are many external influences in today's market force that impair
      the relationship between the pain medicine specialist and the patient, and
      ultimately prevent optimal quality of care. This article explores the ethical
      challenges facing the pain medicine specialist in today's increasingly "business"
      environment and will offer solutions for maintaining the professionalism of pain
      medicine. DISCUSSION: Four commonly encountered bioethical principles in the
      practice of pain medicine are reviewed: beneficence, nonmaleficence, justice, and
      autonomy. The following ethical challenges of the pain medicine specialist are
      reviewed: practicing outside ones specialty area, practice characteristics, the
      consultant role, the economic lure of aggressive intervention, not evaluating for
      and treating comorbid psychopathology, reimbursement pressures, workers'
      compensation, and use of unproven methods. CONCLUSIONS: Solutions offered include
      collegial associations, social responsibility, legislative initiatives, pain
      education, interdisciplinary evaluation and treatment, improved relationships
      with third-party payers, reduced racial disparities, and ethics education. Ethics
      is the "roadmap" that enables the pain medicine specialist to navigate the
      increasingly murky waters of practicing pain management today by maintaining the
      professionalism necessary to combat today's "business" pressures.

PMID- 22882519
TI  - Lack of association between p53 SNP and FISS in a cat population from Germany.
AB  - One recent study indicates a significant association between certain single
      nucleotide polymorphisms (SNPs) in the genomic sequence of feline p53 and feline
      injection-site sarcoma (FISS). The aim of this study was to investigate the
      correlation between a specific nucleotide insertion in p53 gene and FISS in a
      German cat population. Blood samples from 150 German cats were allocated to a
      control group consisting of 100 healthy cats and a FISS-group consisting of 50
      cats with FISS. All blood samples were examined for the presence of the SNP in
      the p53 gene. Results found the T-insertion at SNP 3 in 20.0% of the cats in the
      FISS-group and 19.2% of cats in the control-group. No statistically significant
      difference was observed in allelic distribution between the two groups. Further
      investigations are necessary to determine the association of SNPs in the feline
      p53 gene and the occurrence of FISS. 

PMID- 22882520
TI  - c-myc in Kaposi's sarcoma: analyses by fluorescent in situ hybridization and
      immunohistochemistry.
AB  - BACKGROUND: The c-myc proto-oncogene plays a central role in the regulation of
      cellular transcription, differentiation, and apoptosis, and has been shown to be
      deregulated in many types of human cancer. Recent findings have demonstrated its
      amplification in select vascular neoplasms, such as secondary angiosarcomas,
      suggesting a role in angiogenesis as well. In vitro studies have shown that the c
      Myc protein is an important regulatory molecule of spindle cell proliferation and
      migration in Kaposi's sarcoma (KS). OBJECTIVES: In light of these findings, our
      primary aim was to ascertain whether c-myc, by promoting proliferation and
      angiogenesis, is an essential co-factor in the aetiopathogenesis of KS. We also
      attempted to determine a correlation between immunohistochemical expression of
      the c-Myc protein and c-myc gene copy amplification using fluorescent in situ
      hybridization (FISH). METHODS: Samples analyzed included archival tissue of KS (n
      = 24). PCR for detection of Kaposi's sarcoma-associated herpesvirus DNA was
      performed on all samples of KS. For FISH analyses, a dual-labelled technique was
      employed and probes for the c-myc gene and chromosome 8 were used. The monoclonal
      anti-c-myc antibody, 9E10, was used for immunohistochemical analyses. RESULTS:
      While FISH analyses revealed no amplification of c-myc in any of the cases of KS,
      immunohistochemical analyses revealed positive staining for c-Myc in 13/24 cases
      (54%). CONCLUSIONS: Amplification of the c-myc gene was not witnessed in this
      preliminary study of 24 cases and thus cannot be correlated with the expression
      of the c-Myc protein.

PMID- 22882521
TI  - A big hole and a big heart: an unusual case of esophageal dysphagia.

PMID- 22882522
TI  - Cleaning and modification of intraorally contaminated titanium discs with calcium
      phosphate powder abrasive treatment.
AB  - OBJECTIVE: The aim of this study was to evaluate the cleaning efficiency on
      intraorally contaminated titanium discs by using calcium phosphate and air powder
      abrasive (APA) treatment. The modification of titanium surface (SLA) was
      evaluated and compared with the conventional air powder abrasive methods and
      phosphoric acid. This treatment modality might give new perspectives for peri
      implant surface treatment. MATERIALS AND METHODS: A total of 36 SLA surface
      titanium discs were kept in the human mouth for 48 h by 14 volunteers. The
      intraorally contaminated discs were stained with erythrosine dye to make the
      biofilm visible. Discs were randomly assigned to one of the six groups: APA
      without powder-only water and air (Control). APA with Hydroxylapatite (HA). APA
      with Hydroxylapatite and Calcium Phosphate (HA + TCP). APA with Titanium Dioxide
      (TiO2). APA with EMS Soft Subgingival powder (EMS). Phosphoric Acid. Light
      microscope photos were taken during the treatment. Following the cleaning, the
      residual biofilm, surface changes, and surface chemical content were evaluated
      using Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray Spectroscopy
      (EDS). A systematic random sampling protocol and a point counting method were
      applied for the quantitative evaluation of the remaining biofilm. Multiple
      comparisons within and between groups are performed by Kruskall Wallis test and
      if significant Mann-Whitney U-test as post hoc testing is applied. The
      significance level was P < 0.05. RESULTS: All methods with the exception of
      phosphoric acid could decrease the initial amount of biofilm significantly. Among
      all air powder abrasive treatments, the HA + TCP group showed the best results
      with 99% biofilm removal, followed by HA and EMS powders. The cleaning method
      caused minimal changes to the surface structure. With the exception of the
      control group, all air powder applications caused sharp edges around the grooves
      in the implant surface to be rounded. TiO2 powder caused less change than HA and
      HA + TCP. Phosphoric acid did not cause a visible surface change on the SEM
      photos. Powder particles remnants were observed on and impacted in the titanium
      surface. In the HA and HA + TCP group, a Ca content was observed varying between
      2% and 5%. In the control group, saliva and biofilm-related elements were
      observed. CONCLUSIONS: Using the air powder abrasive method with calcium
      phosphate powders on contaminated titanium discs, an efficient implant cleaning
      and surface modification can be achieved. This method should be further improved
      as it has possible potential to be used as an implant surface treatment method
      for implants involved with peri-implantitis.

PMID- 22882523
TI  - Should soccer and alcohol mix? Alcohol sales during the 2014 World Soccer Cup
      games in Brazil.

PMID- 22882524
TI  - Metabolic adaptations of Pseudomonas aeruginosa during cystic fibrosis chronic
      lung infections.
AB  - Pseudomonas aeruginosa forms chronic infections in the lungs of cystic fibrosis
      (CF) patients, and is the leading cause of morbidity and mortality in patients
      with CF. Understanding how this opportunistic pathogen adapts to the CF lung
      during chronic infections is important to increase the efficacy of treatment and
      is likely to increase insight into other long-term infections. Previous studies
      of P. aeruginosa adaptation and divergence in CF infections have focused on the
      genetic level, both identifying characteristic mutations and patterns of gene
      expression. However, these approaches are not sufficient to fully understand the
      metabolic changes that occur during long-term infection, as metabolic regulation
      is complex and takes place on different biological levels. We used untargeted
      metabolic profiling (metabolomics) of cell supernatants (exometabolome analysis,
      or metabolic footprinting) to compare 179 strains, collected over time periods
      ranging from 4 to 24 years for the individual patients, representing a series of
      mostly clonal lineages from 18 individual patients. There was clear evidence of
      metabolic adaptation to the CF lung environment: acetate production was highly
      significantly negatively associated with length of infection. For amino acids,
      which are available to the bacterium in the lung environment, the tendency of
      isolates to evolve more efficient uptake was related to the biosynthetic cost of
      producing each metabolite; conversely, for the non-mammalian metabolite
      trehalose, isolates had significantly reduced tendency to utilize this compound
      with length of infection. However, as well as adaptation across patients, there
      was also a striking degree of metabolic variation between the different clonal
      lineages: in fact, the patient the strains were isolated from was a greater
      source of variance than length of infection for all metabolites observed. Our
      data highlight the potential for metabolomic investigation of complex phenotypic
      adaptations during infection.

PMID- 22882525
TI  - Prognostic factors for recent-onset interstitial cystitis/painful bladder
      syndrome.
AB  - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? Interstitial cystitis/painful bladder
      syndrome (IC/PBS) comprises pain perceived to be from the bladder, urinary
      urgency and frequency, and nocturia. As diagnosed at present, it is primarily
      identified in adult women. It is a chronic disease yet its natural history has
      not been well studied. In a prospective study of 304 incident female IC/PBS cases
      followed for a median of 33 months after onset, women with baseline chronic
      fatigue syndrome had a worse prognosis for IC/PBS. Mild IC/PBS at baseline was
      the only variable that was directly associated with a good prognosis. OBJECTIVE:
      To identify baseline variables that predict the prognosis of interstitial
      cystitis/painful bladder syndrome (IC/PBS) in women seeking medical care for
      recent onset of this syndrome. SUBJECTS AND METHODS: In a prospective study of
      women with incident IC/PBS (<=12 months of symptoms), we contacted patients at
      intervals and asked standardized questions about IC/PBS symptoms in the previous
      week. Logistic regression analyses assessed baseline variables as predictors of
      mild vs more severe IC/PBS at the last follow-up. RESULTS: Median length of
      follow-up was 33 months after onset of IC/PBS; 304 (97%) patients had at least
      one follow-up assessment. Mild IC/PBS at baseline was the only variable that was
      directly associated with a mild IC/PBS endpoint. Conversely, a history of chronic
      fatigue syndrome (CFS) was inversely associated with a mild endpoint of IC/PBS
      (i.e. individuals with CFS had a worse prognosis for their IC/PBS symptoms).
      CONCLUSIONS: At a median of nearly 3 years after onset, baseline mild IC/PBS was
      directly associated with a milder disease severity. Baseline co-morbid CFS was
      associated with more severe disease. Whether CFS was uniquely associated or
      represented several co-morbid non-bladder syndromes (NBSs) could not be
      determined.

PMID- 22882526
TI  - Identification of predictors of Salmonella shedding in adult horses presented for
      acute colic.
AB  - BACKGROUND: Colic has been associated with shedding of Salmonella. Horses with
      salmonellosis typically develop diarrhea, fever, and leukopenia. Overlooking
      additional predictors may result in failure to detect shedding horses and
      increase environmental contamination. OBJECTIVES: Evaluate associations between
      signalment and clinicopathologic data during early hospitalization and Salmonella
      shedding in horses treated for acute colic. ANIMALS: Horses with acute colic
      admitted to a referral hospital. A total of 59 horses shedding Salmonella
      compared to 108 Salmonella-negative horses. METHODS: Retrospective case-control
      study evaluating patient and Salmonella culture data. Associations between
      variables and Salmonella shedding were identified using logistic regression. Two
      multivariable models were developed pertaining to (1) information available
      within 24 hours of admission and (2) clinical findings that developed later
      during hospitalization. RESULTS: Variables retained for multivariable model 1
      indicated that Warmbloods and Arabians had increased odds for shedding
      Salmonella, as did horses requiring surgery (OR, 2.52; 95% CI, 1.10-5.75) or
      having more severe gastrointestinal disease (OR, 2.59; 95% CI, 1.08-6.20).
      Retained variables for model 2 demonstrated that horses that were treated
      surgically (OR, 1.60; 95% CI, 0.70-3.62), developed fever >103 degrees F (OR,
      2.70; 95% CI, 0.92-7.87), had abnormal leukocyte count (OR, 1.38; 95% CI, 0.61
      3.09), or became inappetent and lethargic (OR, 16.69; 95% CI, 4.08-68.24) had
      increased odds for shedding Salmonella. CONCLUSIONS AND CLINICAL IMPORTANCE: In
      horses with acute colic that present without signs of diarrhea, fever, or
      leukopenia, additional predictors associated with shedding Salmonella could be
      used to more promptly identify horses likely to shed organisms.

PMID- 22882527
TI  - Cutaneous macroglobulinosis: a case series.
AB  - Cutaneous macroglobulinosis is a rare skin manifestation of Waldenstrom
      macroglobulinemia. It is characterized by the deposition of eosinophilic,
      immunoglobulin-derived material in the dermis. It typically presents as pink or
      skin-colored papules favoring the extensor surfaces of the extremities. There are
      11 reported cases of cutaneous macroglobulinosis in the literature. In our
      consultative dermatopathology practice we encountered three additional cases. In
      Case 1, a 41-year-old female with a monoclonal immunoglobulin M (IgM)-kappa
      gammopathy developed skin-colored papules on her extensor extremities, forehead
      and back. Histopathologic and immunohistochemical analyses revealed periodic acid
      Schiff (PAS)-positive pink material in the dermis that stained with IgM. In Case
      2, an 83-year-old female with a monoclonal IgM-lambda paraproteinemia developed
      non-blanching papules and plaques on the lower extremities and cheeks. Skin
      biopsies showed a striking occlusion of the vessels with a PAS-positive
      eosinophilic precipitate, which was also found in the extravascular spaces and
      stained with IgM using direct immunofluorescence (DIF) and immunohistochemical
      stains. In Case 3, an 80-year-old male with Waldenstrom macroglobulinemia
      developed ulcerated papules and nodules on the lower extremities. The biopsy
      findings were similar to those of Case 2. We present a series of three patients
      with cutaneous macroglobulinosis and explore variations in the clinical and
      histopathological findings of this uncommon entity.

PMID- 22882528
TI  - Low intensity laser therapy speeds wound healing in hemophilia by enhancing
      platelet procoagulant activity.
AB  - Our group has previously shown that cutaneous wound healing is delayed and
      histologically abnormal in a mouse model of hemophilia. Hemostasis is not only
      required to stop bleeding at the time of wounding, but also produces bioactive
      substances that promote appropriate inflammatory and proliferative responses
      during healing. Low intensity laser therapy (LILT) has been reported to enhance
      impaired wound healing in a variety of animal and human studies. The current
      studies were conducted to test the hypothesis that LILT can improve healing in a
      hemophilia B mouse model. Three daily treatments with 12 J/sq cm of 650 nm laser
      illumination reduced the time to closure of a 3-mm cutaneous punch biopsy wound
      in the hemophilic mice. All wounds were closed at 13 days in the sham-treated
      hemophilic mice, compared with 10 days in the LILT-treated hemophilic mice, and 9
      days in wild-type mice. While LILT can speed healing by enhancing proliferation
      of cutaneous cells, we found that an additional mechanism likely contributes to
      the efficacy of LILT in the hemophilic mice. LILT enhanced the mechanical
      rigidity and platelet activity of clots formed from human platelet-rich plasma.
      Illumination of isolated platelets increased the mitochondrial membrane potential
      and enhanced binding of coagulation factors to the surface of activated
      platelets. Thus, while LILT can directly promote proliferative responses during
      healing, it also appears to enhance hemostasis in an animal model with impaired
      coagulation. These data suggest that trials of LILT as an adjunct to the usual
      hemostatic therapies in hemophilia are warranted.

PMID- 22882530
TI  - In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new
      platelet additive solution.
AB  - BACKGROUND: Platelets (PLTs) stored in additive solutions (PASs) may reduce the
      risk of several plasma-associated adverse transfusion reactions such as allergic
      reactions and potentially transfusion-associated lung injury. The objective of
      this study was to determine the in vitro characteristics and the in vivo
      radiolabeled recovery and survival of apheresis PLTs (APs) stored in a new PAS
      and compare the latter to Food and Drug Administration (FDA) criteria. STUDY
      DESIGN AND METHODS: Hyperconcentrated APs were collected from healthy subjects in
      a paired crossover study comparing PAS (35% plasma) and 100% plasma-stored APs
      (Part 1) up to 7 days and, in Part 2, to determine the in vivo recovery and
      survival of PAS stored AP at 5 days compared to fresh PLT controls. In vitro and
      in vivo assays were performed following standard methods. RESULTS: Sixty-six and
      25 evaluable subjects successfully completed Parts 1 and 2, respectively. pH for
      PAS AP was maintained above 6.6 for 5 days of storage. P-selectin values were
      consistent with published values for commonly transfused PLT products. The PAS in
      vivo PLT recovery (54.3 +/- 8.1%) was 86.7% of the fresh control, and survival
      (6.4 +/- 1.3 days) was 78.0% of the fresh control, both meeting the FDA
      performance criteria. CONCLUSION: APs stored in PAS with 35% plasma carryover
      maintained pH over 5 days of storage and met current FDA criteria for
      radiolabeled recovery and survival. The use of PAS for storage of single-donor
      PLTs in clinical practice represents an acceptable transfusion product that
      reduces the volume of plasma associated with PLT transfusion.

PMID- 22882531
TI  - Quercetin improves bone strength in experimental biliary cirrhosis.
AB  - AIM:   Metabolic bone disorders and reduced bone mass are common complications in
      patients with biliary cirrhosis. As a result of there being no clear etiology, no
      specific therapy has been established yet. Previous studies have reported that
      quercetin, a plant-derived flavonoid, might improve bone quality. The present
      study was designed to investigate the effect of quercetin on bone strength of
      biliary cirrhotic rats. METHODS:   Twenty-four male Sprague-Dawley rats aged 6-7
      months were randomized into three groups of eight. One group served as control
      (sham operated), while the other two groups underwent a complete bile duct
      ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline
      phosphatase, alanine aminotransferase and aspartate aminotransferase were
      measured in animal blood samples to confirm the occurrence of cirrhosis in the
      BDL rats. Then, one of the BDL groups received placebo and the other one was
      injected once a day with 150 umol/kg of quercetin for 4 weeks. At the end of the
      study, femora were removed and tested for bone strength and histomorphometric
      parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide
      of type I collagen, calcium and phosphorus were determined as bone turnover
      markers. RESULTS:   Femur breaking strength was dramatically lower in the BDL
      group compared with control. However, receiving quercetin could reverse the
      deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could
      noticeably elevate osteocalcin as a bone formation marker. CONCLUSION:   These
      data suggest that quercetin can significantly improve bone strength particularly
      due to increasing bone formation in biliary cirrhosis.

PMID- 22882529
TI  - The putative auxin efflux carrier OsPIN3t is involved in the drought stress
      response and drought tolerance.
AB  - The phytohormone auxin plays a critical role in plant growth and development, and
      its spatial distribution largely depends on the polar localization of the PIN
      FORMED (PIN) auxin efflux carrier family members. In this study, we identify a
      putative auxin efflux carrier gene in rice, OsPIN3t, which acts in auxin polar
      transport but is also involved in the drought stress response in rice. We show
      that OsPIN3t-GFP fusion proteins are localized in plasma membranes, and this
      subcellular localization changes under 1-N-naphthylphthalamic acid (NPA)
      treatment. The tissue-specific expression patterns of OsPIN3t were also
      investigated using a beta-glucuronidase (GUS) reporter, which showed that OsPIN3t
      was mainly expressed in vascular tissue. The GUS activity in OsPIN3tpro::GUS
      plants increased by NAA treatment and decreased by NPA treatment. Moreover,
      knockdown of OsPIN3t caused crown root abnormalities in the seedling stage that
      could be phenocopied by treatment of wild-type plants with NPA, which indicated
      that OsPIN3t is involved in the control of polar auxin transport. Overexpression
      of OsPIN3t led to improved drought tolerance, and GUS activity significantly
      increased when OsPIN3tpro::GUS plants were subjected to 20% polyethylene glycol
      stress. Taken together, these results suggest that OsPIN3t is involved in auxin
      transport and the drought stress response, which suggests that a polar auxin
      transport pathway is involved in the regulation of the response to water stress
      in plants.

PMID- 22882532
TI  - Guinea pig skin, a model for epidermal cellular and molecular changes induced by
      UVR in vivo and in vitro: effects on Mycobacterium bovis Bacillus Calmette-Guerin
      vaccination.
AB  - Previously, we reported that ultraviolet B-radiation (UVR) suppressed Bacillus
      Calmette-Guerin (BCG) vaccine-induced resistance to Mycobacterium tuberculosis in
      guinea pigs (GP). Herein, we investigated the cellular and molecular changes
      within the irradiated GP epidermis and the in vivo effect of supernatants from UV
      irradiated (200 J m(-2)) epidermal cells (UV-sup) on M. bovis BCG vaccination.
      UVR increased the number of nucleated keratinocytes in the skin, but caused a
      decrease in the proportions of CD25(+)T cells. In the spleen, UVR resulted in a
      decrease in the proportions of T-cell subsets including CD25(+)T cells, and major
      histocompatibility complex (MHC) class II(+) and CD14(+) cells. Similarly,
      significant up-regulation of several cytokine mRNAs including IL-10 was also
      observed. Furthermore, UV-sup significantly reduced the MHC class II expression
      in peritoneal cells and reduced T-cell proliferation to ConA. The proliferation
      to purified protein derivative (PPD) was restored to normal levels by anti-IL-10
      antibody. The UV-sup when injected into BCG-vaccinated GP significantly
      diminished the skin test response and T-cell proliferation to PPD and up
      regulated the expression of IL-10, IL-4, IL-1beta and Foxp3 mRNAs in the lymph
      node or spleen. Thus, whole body UVR induces profound cellular and molecular
      changes and injection of UV-sup from epidermal cells mimics the effect of whole
      body UVR in BCG-vaccinated GP.

PMID- 22882533
TI  - Cognitive dysfunction: an emerging concept of a new diabetic complication in the
      elderly.
AB  - The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is
      likely to continue. Recent advances suggest that T2DM is a risk factor for
      cognitive decline. We are now encountering novel complications of T2DM, namely
      cognitive dysfunction and dementia. Although the treatment strategy for diabetic
      patients with neurocognitive dysfunction has received a great deal of attention,
      the appropriate level of glycemic control for the prevention of the development
      and/or progression of cognitive decline in elderly diabetic patients remains to
      be elucidated. Another issue in diabetic treatment in patients with cognitive
      dysfunction is the selection of medicines. The best choice and combination of
      antidiabetic medications for the preservation of cognition should also be
      studied. Ample studies suggest that exercise helps to preserve cognitive
      function, although existing evidence does not necessarily indicate its
      effectiveness exclusively in diabetic patients. Exercise is a helpful non
      pharmacological therapy. Considering the progressive aging of the worldwide
      population, more research to investigate the best way to manage this population
      is important.

PMID- 22882534
TI  - A review of risk factors for oral cavity cancer: the importance of a standardized
      case definition.
AB  - The aim of this work is to review the literature on risk factors of oral cavity
      cancer with a special attention to the definition of the cases, in order to
      highlight special features of these cancers and of their subsites. PubMed
      database was systematically searched to access relevant articles published
      between 1980 and 2010. Reference lists of selected papers were examined to
      identify further articles. One hundred and two studies met the inclusion
      criteria. Their results were difficult to compare because of the lack of
      uniformity in defining oral cavity. In addition, few studies examined risk
      factors other than alcohol and tobacco, and studies differentiating between
      subsites were rare. Despite these limitations, some characteristics of oral
      cavity cancers may be emphasized: smoked tobacco seems to be a stronger risk
      factor for oral cavity cancer than alcohol, and the floor of the mouth seems to
      be more sensitive to the harmful effects of alcohol and smoked tobacco. Studies
      limited strictly to oral cavity cancers and distinguishing between subsites are
      needed to better understand the aetiology of these cancers, and better define
      risk groups to target prevention efforts and screening.

PMID- 22882535
TI  - Variations in testosterone pathway genes and susceptibility to testicular cancer
      in Norwegian men.
AB  - Imbalance between the oestrogen and androgen levels in utero is hypothesized to
      influence testicular cancer (TC) risk. Thus, variation in genes involved in the
      action of sex hormones may contribute to variability of an individual's
      susceptibility to TC. Mutations in testosterone pathway genes may alter the level
      of testosterone in vivo and hypothetically the risk of developing TC. Luteinizing
      hormone receptor (LHR), 5alpha-reductase II (SRD5A2) and androgen receptor (AR)
      are key elements in androgen action. A case-control study comprising 651 TC cases
      and 313 controls in a Norwegian population was conducted for investigation of
      polymorphisms in the LHR, SRD5A and AR genes and their possible association with
      TC. A statistical significant difference was observed in patients being
      heterozygous for the LHR Asn312Ser polymorphism when comparing genotypes between
      all TC cases and controls (OR = 0.66, 95% CI = 0.48-0.89, p(adj) = 0.049). No
      statistically significant difference between the histological subtypes seminoma
      and non-seminoma was observed. Our results may suggest a possible association
      between genetic variation in the LHR gene and the risk of developing TC.

PMID- 22882536
TI  - Schistosoma real-time PCR as diagnostic tool for international travellers and
      migrants.
AB  - OBJECTIVE: To evaluate the use of a genus-specific PCR that combines high
      sensitivity with the detection of different Schistosoma species for diagnosis in
      international travellers and migrants in comparison to standard microscopy.
      METHODS AND RESULTS: The genus-specific real-time PCR was developed to target the
      28S ribosomal RNA gene of the major human Schistosoma species. It was validated
      for analytical specificity and reproducibility and demonstrated an analytical
      sensitivity of 0.2 eggs per gram of faeces. Its diagnostic performance was
      further evaluated on 152 faecal, 32 urine and 38 serum samples from patients
      presenting at the outpatient clinic of the Institute of Tropical Medicine in
      Antwerp (Belgium). We detected Schistosoma DNA in 76 faecal (50.0%) and five
      urine (15.6%) samples of which, respectively, nine and one were not detected by
      standard microscopy. Only two of the 38 serum samples of patients with confirmed
      schistosomiasis were positive with the presently developed PCR. Sequence analysis
      on positive faecal samples allowed identification of the Schistosoma species
      complex. CONCLUSION: The real-time PCR is highly sensitive and may offer added
      value in diagnosing imported schistosomiasis. The genus-specific PCR can detect
      all schistosome species that are infectious to humans and performs very well with
      faeces and urine, but not in serum.

PMID- 22882538
TI  - Serum neopterin levels in female dogs with malignant mammary tumours.
AB  - In this study, we have determined serum neopterin levels in female dogs with
      primary malignant mammary tumours. The study involved 50 female dogs which had a
      malignant mammary tumours removed surgically (32 animals with carcinoma, 12
      animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy
      female dogs. Serum neopterin levels were determined using a commercial ELISA kit.
      The mean neopterin levels were lower in the malignant tumour groups than in
      healthy animals but differences were statistically significant only in carcinoma
      and sarcoma groups. The decrease of neopterin levels in animals with malignant
      mammary tumours may suggest their decreased cellular immunity. Moreover, it might
      indicate that decreased activity of cellular mechanisms of the anti-neoplastic
      response is one of the factors associated with the development and course of
      malignant mammary tumours in female dogs; however, further studies are necessary.

PMID- 22882537
TI  - Novel insights into the role of S100A8/A9 in skin biology.
AB  - S100A8 and S100A9 belong to the damage-associated molecular pattern molecules.
      They are upregulated in a number of inflammatory skin disorders. Owing to their
      abundance in myeloid cells, the main function of S100A8/A9 has been attributed to
      their role in inflammatory cells. However, it is becoming increasingly clear that
      they also exert important roles in epithelial cells. In this review, we discuss
      the context-dependent function of S100A8/A9 in epithelial cells and their impact
      on wound healing, psoriasis and other skin diseases.

PMID- 22882539
TI  - Laparoscopic bilateral native nephrectomies with simultaneous kidney
      transplantation.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Extirpation of polycystic kidneys for
      various medical reasons has been performed using many different approaches in
      attempts to limit morbidity from such a large operation. In indicated patients,
      it has usually been offered in a staged approach with renal transplantation to
      avoid graft complications. We published the first case of simultaneous
      laparoscopic bilateral native nephrectomy with kidney transplant in 2008. The
      present study shows our continued experience with offering this minimally
      invasive, single surgery alternative. The results are comparable to a staged
      laparoscopic approach with significantly shorter total hospital stay and one
      recovery for the patient and his/her family. OBJECTIVE: * To analyse the
      perioperative outcomes of native bilateral laparoscopic nephrectomy (BLN) with
      simultaneous kidney transplantation. PATIENTS AND METHODS: * From November 2000
      to April 2011, 37 patients were seen for renal failure secondary to autosomal
      dominant polycystic kidney disease (ADPKD) and underwent renal transplant with
      native nephrectomies at a single tertiary academic centre. * In all, 15 patients
      underwent BLN for ADPKD followed by simultaneous kidney transplantation. * The
      other 22 patients underwent BLN for ADPKD with kidney transplant performed at a
      separate setting. * Demographic data, perioperative outcomes, complications
      regardless of need for intervention, and graft function were analysed in both
      groups. RESULTS: * The combined surgery was completed without intraoperative
      complication in all cases. * The median total operative duration was 372 min,
      estimated blood loss was 300 mL with two patients requiring transfusion, and the
      median (range) hospital stay was 5 (3-7) days. * All patients had immediate graft
      function with additional relief of compressive symptoms. * In comparison to our
      staged cohort, the simultaneous group had a significantly shorter total hospital
      stay. * All other outcomes and complication rates were comparable. CONCLUSION: *
      In ADPKD, a less invasive laparoscopic approach for native nephrectomies with
      simultaneous renal transplant offers comparable morbidity without graft
      compromise and the convenience of one operation and one recovery for the patient.

PMID- 22882540
TI  - Preliminary exploration of the clinical features of Chinese patients with skin
      malignancies and premalignancies: a retrospective study of 1420 cases from Peking
      University First Hospital.
AB  - BACKGROUND: The epidemiological and clinical characterization data of skin
      malignancies and premalignancies in Chinese population is scarce and inadequate.
      OBJECTIVE: To systematically investigate the clinical features and the trend of
      skin malignancies and premalignancies in 1420 Chinese cases. METHODS: A total of
      1398 patients (presenting 1420 skin tumours) were included. Clinical and
      demographic information for every individual was collected, including age, age of
      onset, sex, lesion location, disease duration and tumour histology, which was
      analyzed for each type of skin tumours. RESULTS: The number of skin malignancies
      and premalignancies increased over time, with Basal cell carcinoma (BCC) as the
      most common type (30.5%). The majority of the patients were above 60 years of age
      both at onset and at diagnosis (52.8% and 62.9%, respectively), yet around one
      third of patients were between 35-59 years (35.3% and 31.2%, respectively). Skin
      malignancies and premalignancies were mainly located in the head and neck
      (58.6%), followed by the trunk (18.3%) and the extremities (15.0%). Of all BCCs,
      nodular BCC was the most common histologic subtype (62.8%), while 15.8% were
      classified as aggressive subtypes. Malignant melanoma (MM) comprised the lowest
      proportion of 3.7%, with 75% located on extremities. The diagnostic accordance
      rates varied from 49.5% to 90.4%, with BCC being 67.9%. CONCLUSIONS: The clinical
      features of skin malignancies and premalignancies in this study showed some
      similarities with those observed in Caucasian and other Asian populations, with
      several distinguished features in Chinese patients also being recognized. Closer
      attention to suspicious lesions in young and middle-aged people is needed.

PMID- 22882541
TI  - Early HER2 dysregulation in gastric and oesophageal carcinogenesis.
AB  - AIMS: To explore human epidermal growth factor receptor 2 (HER2) status in the
      histological phenotypes [metaplasia, intraepithelial neoplasia (IEN, i.e.
      dysplasia), and adenocarcinoma] involved in the morphogenesis of both intestinal
      type gastric cancer (GC) and Barrett's adenocarcinoma (BAc). METHODS AND RESULTS:
      A consecutive series of 275 samples of stomach and oesophagus tissue
      (representing the whole spectrum of the phenotypic changes involved in gastric
      and Barrett's carcinogenesis) was studied. HER2 status was assessed by applying
      two immunohistochemistry (IHC) protocols, using the antibodies 4B5 and CB11. Dual
      colour silver chromogenic in-situ hybridization (SISH) was also performed on the
      same tissue samples. In both oesophageal and gastric samples, the rate of HER2
      overexpression rose significantly from low-grade to high-grade IEN to
      adenocarcinoma (P < 0.001), with the two IHC protocols showing consistent
      staining (consistency 95%; k = 0.78; P < 0.001). Intratumour heterogeneity was
      documented in both GC and BAc (using both IHC protocols). The rate of HER2
      amplification (using SISH) increased significantly along with IEN
      dedifferentiation (P < 0.001). Neither native nor metaplastic mucosa samples
      (obtained from either stomach or oesophagus) ever showed HER2 amplification.
      There was excellent agreement between HER2 amplification and protein
      overexpression (both IHC protocols: SISH/4B5--consistency 97.8%, k = 0.89, P <
      0.001; SISH/CB11-consistency 97.8%, k = 0.91, P < 0.001). CONCLUSIONS: There is
      early involvement of HER2 dysregulation (amplification and protein
      overexpression) in both gastric (intestinal-type) and Barrett's oncogenesis.

PMID- 22882542
TI  - Intermittent hydrostatic pressure enhances growth factor-induced chondroinduction
      of human adipose-derived mesenchymal stem cells.
AB  - Hydrostatic pressure (HP) plays an essential role in regulating function of
      chondrocytes and chondrogenic differentiation. The objective of this study was to
      examine effects of intermittent HP on chondrogenic differentiation of human
      adipose-derived mesenchymal stem cells (hASCs) in the presence or absence of
      chemical chondrogenic medium. Cells were isolated from abdominal fat tissue and
      confirmed for expression of ASC surface proteins and differentiation potential.
      Passage 3 pellets were treated with chemical (growth factor), mechanical (HP of 5
      MPa and 0.5 Hz with duration of 4 h/day for 7 consecutive days), and combined
      chemical-mechanical stimuli. Using real-time polymerase chain reaction, the
      expression of Sox9, collagen II, and aggrecan as three major chondrogenic markers
      were quantified among three experimental groups and compared to those of stem
      cells and human cartilage tissue. In comparison to the chemical and mechanical
      groups, the chemical-mechanical group showed the highest expression for all three
      chondrogenic genes close to that of cartilage tissue. Results show the beneficial
      role of intermittent HP on chondrogenic differentiation of hASCs, and that this
      loading regime in combination with chondrogenic medium can be used in cartilage
      tissue engineering.

PMID- 22882543
TI  - Transient sputum eosinophilia may occur over time in non-eosinophilic asthma and
      this is not prevented by salmeterol.
AB  - BACKGROUND AND OBJECTIVE: Symptomatic, steroid-naive asthmatic patients may have
      low sputum eosinophil numbers. The aim of the study was to determine whether low
      sputum eosinophil numbers persisted over time, during treatment with salmeterol
      monotherapy. METHODS: Forty steroid-naive, symptomatic asthmatic patients, with
      sputum eosinophils <3%, were randomized to receive open-label salmeterol (50 ug
      twice a day, n = 30) or fluticasone (125 ug twice a day, n = 10) and were then
      assessed at 1, 3 and 6 months. All patients underwent spirometry, a methacholine
      challenge test and sputum induction at each visit. Symptom scores and peak
      expiratory flow were recorded throughout the study. Patients were permitted to
      withdraw from the study at any time, if they experienced exacerbations or
      deterioration of symptoms. RESULTS: The average sputum eosinophil percentage
      remained normal (<=1.9%) in both groups over the study period. The eosinophil
      percentages were <=1.9% in 65 of the 80 samples obtained from salmeterol-treated
      patients throughout the study period. Eight patients had an asthma exacerbation
      or deterioration, during which one developed sputum eosinophilia. Twelve
      patients, 11 of whom were randomized to salmeterol and one to fluticasone,
      developed transient sputum eosinophilia at least once during the study. This was
      not associated with asthma exacerbation (except for one patient). Sputum
      neutrophil percentage did not change in either group. CONCLUSIONS: Low sputum
      eosinophil numbers persisted over 6 months in a majority of patients with non
      eosinophilic asthma who received salmeterol monotherapy. However, transient
      sputum eosinophilia occurred in 40% indicating that non-eosinophilic asthma may
      not be a stable phenotype.

PMID- 22882544
TI  - Mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus.

PMID- 22882545
TI  - Killer whale ecotypes: is there a global model?
AB  - Killer whales, Orcinus orca, are top predators occupying key ecological roles in
      a variety of ecosystems and are one of the most widely distributed mammals on the
      planet. In consequence, there has been significant interest in understanding
      their basic biology and ecology. Long-term studies of Northern Hemisphere killer
      whales, particularly in the eastern North Pacific (ENP), have identified three
      ecologically distinct communities or ecotypes in that region. The success of
      these prominent ENP studies has led to similar efforts at clarifying the role of
      killer whale ecology in other regions, including Antarctica. In the Southern
      Hemisphere, killer whales present a range of behavioural, social and
      morphological characteristics to biologists, who often interpret this as evidence
      to categorize individuals or groups, and draw general ecological conclusions
      about these super-predators. Morphologically distinct forms (Type A, B, C, and D)
      occur in the Southern Ocean and studies of these different forms are often
      presented in conjunction with evidence for specialised ecology and behaviours.
      Here we review current knowledge of killer whale ecology and ecotyping globally
      and present a synthesis of existing knowledge. In particular, we highlight the
      complexity of killer whale ecology in the Southern Hemisphere and examine this in
      the context of comparatively well-studied Northern Hemisphere populations. We
      suggest that assigning erroneous or prefatory ecotypic status in the Southern
      Hemisphere could be detrimental to subsequent killer whale studies, because
      unsubstantiated characteristics may be assumed as a result of such
      classification. On this basis, we also recommend that ecotypic status
      classification for Southern Ocean killer whale morphotypes be reserved until more
      evidence-based ecological and taxonomic data are obtained.

PMID- 22882547
TI  - Mandibular implant-supported removable partial denture with distal extension: a
      systematic review.
AB  - The aim of this article is to investigate patient satisfaction, survival rate of
      implants, and prosthetic complications or maintenance for rehabilitation with
      removable partial dentures associated with implants in mandibular Kennedy class I
      and II cases. A systematic literature review was conducted by three independent
      reviewers including articles published from January 1981 through September 2011.
      Medline and Cochrane Library electronic databases were used in addition to hand
      searching to assess clinical outcomes for mandibular implant-supported removable
      partial denture with distal extension. This review yielded 1751 records that were
      narrowed down to 5. The studies revealed implant survival rates ranging from 95%
      to 100% with one failure reported of 98 implants. The removable partial dentures
      associated with implant in mandibular free-end arches showed some complications
      and need of repair for relining, pitting of the healing abutment, replacement of
      resilient component of the attachment, damage in framework, screw loosening and
      damage in acrylic denture base. Patient satisfaction was evaluated through a five
      point questionnaire, and results ranged between 4.12 and 5.0, considering 1 as
      the least favourable situation. The literature review showed increase in patient
      satisfaction and high survival rates of implants associated with mandibular
      removable partial dentures with distal extensions. However, some complications
      and need of prosthetic repair were reported. Although this treatment approach
      could represent a low-cost and beneficial rehabilitation for free-end mandibular
      ridges, the lack of controlled and randomised well-designed clinical trials
      suggests further studies with more representative samples to validate the
      outcomes of this treatment modality.

PMID- 22882549
TI  - Acute azotemia as a predictor of mortality in dogs and cats.
AB  - BACKGROUND: Acute kidney injury (AKI) has been shown to be a predictor of
      mortality in human medicine. Published studies in the veterinary literature
      evaluating relative changes in serum creatinine concentration as a prognostic
      factor are limited. OBJECTIVE: To evaluate an AKI grading system based on serum
      creatinine concentration to determine if it correlates with outcome prediction in
      dogs and cats. ANIMALS: Six hundred forty-five dogs and 209 cats that had at
      least 2 serum creatinine concentration measurements measured within 7 days.
      METHODS: Retrospective study. Dogs and cats with an initial serum creatinine
      concentrations of <= 1.6 mg/dL and that had more than 1 concentration measured
      within 2, 3, and 7 days were placed into levels (0-2) based on absolute changes.
      Mortality then was determined at 30 and 90 days. RESULTS: Based on odds ratios
      calculated with a 95% confidence interval, dogs placed in level 1 within 2 days
      were approximately 3 times more likely to die within 90 days. Dogs placed in
      level 2 within 2, 3, or 7 days were approximately 3 times more likely to die
      within 30 or 90 days. Cats placed in level 2 within 3 or 7 days were
      approximately 3 times more likely to die at 30 days and 4 times more likely to
      die if placed in this level within 7 days. If placed in level 2 within 2 or 3
      days, cats were approximately 3 times more likely to die within 90 days.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Detecting increasing severity of azotemia
      helps predict mortality in dogs and cats.

PMID- 22882550
TI  - Attitudes of general dental practitioners towards implant dentistry in an
      environment with widespread provision of implant therapy.
AB  - OBJECTIVES: To determine attitudes of general dental practitioners in a community
      where provision dental implants is a well-known treatment modality; and to
      identify variations in the attitudes with respect to dentists' factors, training
      factors and implant provision factors. METHODS: A questionnaire survey to a
      random sample of registered dentists In Hong Kong was performed. Attitudes
      towards implant dentistry with respect to (i) perceived superiority of implant
      therapy, (ii) perceived outcomes of dental implant therapy, (iii) perceived
      complications & maintenance issues and (iv) placement issues were ascertained. In
      addition, information was collected on dentists' factors, training factors and
      implant provision factors. Variations in attitudes towards implant dentistry were
      explored in bivariate and regression analyses. RESULTS: Among eligible
      practitioners (n = 246), the response rate was 46.3%. Dentists perceived implants
      to be superior to conventional prostheses for the replacement of a single missing
      posterior tooth (80%, 67) and likewise, for the replacement of a single missing
      anterior tooth (67%, 67), P < 0.05. Variations in attitudes with respect to
      attitudes exists with respect to dentists' factors (years in practice [P <
      0.05]), place of graduation (P < 0.05); implant trainings factors ("hand-on"
      training [P < 0.05]); number of days of training (P < 0.05) and implant
      experience factors (Number of patients treated [P < 0.05]) and number of implants
      placed (P < 0.05). CONCLUSIONS: In a community where provision of dental implants
      is widespread among its General Dental Practitioners (GDPs), their attitudes are
      not wholly in line with evidence-based knowledge. Variations in their attitudes
      existed with respect to dentist factors, training and experience issues.

PMID- 22882546
TI  - Genomic determinants of sporulation in Bacilli and Clostridia: towards the
      minimal set of sporulation-specific genes.
AB  - Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia
      and Negativicutes, include numerous members that are capable of producing heat
      resistant endospores. Spore-forming firmicutes include many environmentally
      important organisms, such as insect pathogens and cellulose-degrading industrial
      strains, as well as human pathogens responsible for such diseases as anthrax,
      botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus
      subtilis, sporulation involves over 500 genes, many of which are conserved among
      other bacilli and clostridia. This work aimed to define the genomic requirements
      for sporulation through an analysis of the presence of sporulation genes in
      various firmicutes, including those with smaller genomes than B. subtilis.
      Cultivable spore-formers were found to have genomes larger than 2300 kb and
      encompass over 2150 protein-coding genes of which 60 are orthologues of genes
      that are apparently essential for sporulation in B. subtilis. Clostridial spore
      formers lack, among others, spoIIB, sda, spoVID and safA genes and have non
      orthologous displacements of spoIIQ and spoIVFA, suggesting substantial
      differences between bacilli and clostridia in the engulfment and spore coat
      formation steps. Many B. subtilis sporulation genes, particularly those encoding
      small acid-soluble spore proteins and spore coat proteins, were found only in the
      family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of
      sporulation genes, compiled in this work, confirm the presence of a common
      sporulation gene core, but also illuminate the diversity of the sporulation
      processes within various lineages. These profiles should help further
      experimental studies of uncharacterized widespread sporulation genes, which would
      ultimately allow delineation of the minimal set(s) of sporulation-specific genes
      in Bacilli and Clostridia.

PMID- 22882551
TI  - The first example of a patient with etoricoxib-induced immune hemolytic anemia.
AB  - BACKGROUND: Etoricoxib, a selective inhibitor of cyclooxygenase 2, is
      increasingly used in pain relief. Here, we report the first case of etoricoxib
      induced immune hemolytic anemia. STUDY DESIGN AND METHODS: An 84-year-old male
      patient developed anemia 1 week after treatment with etoricoxib. There was no
      evidence of hemoglobinemia or hemoglobinuria. Administration of the drug was
      halted, and the patient recovered without further complications. RESULTS: The
      patient's red blood cells (RBCs) were found to be strongly coated with
      immunoglobulin G and C3d. Eluted antibodies and dialyzed serum from the patient
      were not reactive with untreated RBCs, but with etoricoxib-treated RBCs, RBCs in
      the presence of etoricoxib, urine containing drug metabolites (ex vivo antigen),
      and two of four additional COX inhibitor drugs analyzed. DISCUSSION: Although the
      causative antibodies were drug dependent usually leading to abrupt and
      intravascular hemolysis, the patient only gradually developed anemia. These
      findings together with a positive direct and indirect antiglobulin test may lead
      to confusion with autoimmune hemolytic anemia of warm type. A nonreactive eluate
      was the key serologic finding in identifying drug-induced immune hemolytic anemia
      in this case. CONCLUSION: Etoricoxib should be considered as a risk in the
      development of immune hemolytic anemia, with the causative antibodies potentially
      reacting with other COX inhibitors.

PMID- 22882552
TI  - Early repolarization, rare diseases, and the utility of bayesian analysis.

PMID- 22882553
TI  - Enhanced recovery after surgery versus conventional care in colonic and rectal
      surgery.
AB  - INTRODUCTION: Enhanced recovery after surgery (ERAS) programmes have been shown
      to improve outcomes after colonic surgery. However, there is less evidence
      supporting ERAS in rectal surgery. The aim of this study was to compare outcomes
      of conventional perioperative care with those of an ERAS pathway including both
      colonic and rectal surgery patients. METHODS: Outcomes of patients undergoing
      elective colorectal surgery at Christchurch Hospital within the ERAS pathway were
      compared with patients receiving conventional perioperative care over a 2-year
      period. A retrospective analysis was conducted, including primary and total
      length of stay (LOS), readmission, complication and mortality rate. RESULTS: A
      total of 240 patients undergoing colorectal surgery were included; 160 patients
      received conventional perioperative care and 80 patients were managed within the
      ERAS pathway. Primary and total LOS were shorter in the ERAS group (6 versus 7
      days, P = 0.0004, 7 versus 10 days, P = 0.0003, respectively). Re-admission and
      complication rates were not significantly different between the groups. There was
      one death (in the conventional care group) within 30 days. Patients undergoing
      rectal surgery within the ERAS pathway did not show any difference in primary
      LOS, readmission or complication rate although median total LOS was significantly
      reduced (7 versus 10 days, P = 0.0457). CONCLUSION: Patients undergoing elective
      colorectal surgery managed within the ERAS pathway had shorter hospital stays
      without increased morbidity or mortality. Differences were less pronounced in the
      rectal surgery subgroup and further research is needed to investigate the use of
      ERAS pathways for patients undergoing elective rectal surgery.

PMID- 22882554
TI  - Cardiac resynchronization therapy: a breakthrough in heart failure management.
AB  - Heart failure is now considered an epidemic. In patients with heart failure,
      electrical and mechanical dyssynchrony, evident primarily as prolongation of the
      QRS-complex on the surface electrocardiogram, is associated with detrimental
      effects on the cardiovascular system at several levels. In the past 10 years,
      studies have demonstrated that by stimulating both cardiac ventricles
      simultaneously, or almost simultaneously [cardiac resynchronization therapy
      (CRT)], the adverse effects of dyssynchrony can be overcome. Here, we provide a
      comprehensive overview of different aspects of CRT including the rationale behind
      and evidence for efficacy of the therapy. Issues with regard to gender effects
      and patient follow-up as well as a number of unresolved concerns will also be
      discussed.

PMID- 22882556
TI  - The study of fish diseases. Editorial.

PMID- 22882558
TI  - Lipid profile is associated with the incidence of cognitive dysfunction in viral
      cirrhotic patients: A data-mining analysis.
AB  - AIM:   Cognitive dysfunction (CD) is frequently observed in cirrhotic patients.
      However, the biochemical profiles associated with CD remain unclear. We
      investigated the biochemical profiles associated with the incidence of CD in
      cirrhotic patients by using multivariate analyses, including a decision-tree
      algorithm. METHODS:   In this study, 27 viral cirrhotic patients were enrolled.
      All subjects underwent neuropsychiatric tests; two or more abnormal results were
      defined as CD. A logistic regression model was used for multivariate stepwise
      analysis. A decision-tree algorithm was constructed, and the categorical
      differences based on the decision-tree model were analyzed by chi(2) -tests.
      RESULTS:   Multivariate stepwise analysis showed the levels of total bilirubin,
      triglycerides and free fatty acids (FFA) as independent bioparameters associated
      with the incidence of CD in cirrhotic patients. The decision-tree algorithm
      showed that among patients with FFA of 514 mEq/L or more, 77.8% had CD.
      Meanwhile, among patients with FFA of less than 514 mEq/L and triglycerides of
      106 mg/dL or more, 20.0% had CD. The sensitivity, specificity and accuracy for
      the incidence of CD using the lipid profile (FFA >514 mEq/L or triglycerides <106
      mg/dL) were 85.7% (12/14), 61.5% (8/13) and 74.1% (20/27), respectively.
      CONCLUSION:   The levels of total bilirubin, FFA and triglycerides are
      independently associated with the incidence of CD in cirrhotic patients. In
      addition, a decision-tree algorithm revealed that FFA of more than 514 mEq/L or
      triglycerides of less than 106 mg/dL is a profile associated with the incidence
      of CD. Thus, this lipid profile could be a possible screening bioparameter for CD
      in cirrhotic patients.

PMID- 22882557
TI  - A spectroscopic survey of substituted indoles reveals consequences of a
      stabilized 1Lb transition.
AB  - Although tryptophan is a natural probe of protein structure, interpretation of
      its fluorescence emission spectrum is complicated by the presence of two
      electronic transitions, (1)L(a) and (1)L(b). Theoretical calculations show that a
      point charge adjacent to either ring of the indole can shift the emission
      maximum. This study explores the effect of pyrrole and benzyl ring substitutions
      on the transitions' energy via absorption and fluorescence spectroscopy, and
      anisotropy and lifetime measurements. The survey of indole derivatives shows that
      methyl substitutions on the pyrrole ring effect (1)L(a) and (1)L(b) energies in
      tandem, whereas benzyl ring substitutions with electrophilic groups lift the
      (1)L(a)/(1)L(b) degeneracy. For 5- and 6-hydroxyindole in cyclohexane, (1)L(a)
      and (1)L(b) transitions are resolved. This finding provides for (1)L(a) origin
      assignment in the absorption and excitation spectra for indole vapor. The 5- and
      6-hydroxyindole excitation spectra show that despite a blue-shifted emission
      spectrum, both the (1)L(a) and (1)L(b) transitions contribute to emission.
      Fluorescence lifetimes of 1(0) ns for 5-hydroxyindole are consistent with a
      charge acceptor-induced increase in the nonradiative rate (1).

PMID- 22882559
TI  - Model of functional performance in obese elderly people with chronic obstructive
      pulmonary disease.
AB  - PURPOSE: To test a theoretically and empirically supported model of the
      relationships among percent truncal fat (truncal obesity); disease severity
      (carbon monoxide diffusing capacity [DLCO]); symptoms (dyspnea); functional
      capacity (6-min walk test distance); and functional performance (functional
      performance index) of elderly people with chronic obstructive pulmonary disease
      (COPD). DESIGN AND METHOD: A model of functional performance was proposed using a
      multidimensional framework as expounded by Leidy, and incorporating Wilson and
      Cleary's model for the relationship between symptoms and functional status. Path
      analysis was used to examine the relationships among variables. The researchers
      used a descriptive, cross-sectional design. Subjects were phone screened and
      completed electrocardiography, physical examination, spirometry testing, and a 4
      min walk test as part of initial screening. Enrolled subjects completed a whole
      body dual-energy x-ray absorptiometry scan to measure truncal obesity, 6-min walk
      test, upper body functional performance test, and questionnaires. Subjects were
      grouped into normal weight, overweight, or obese according to body mass index.
      RESULTS: The sample consisted of 76 people 55 years of age and older with mild to
      severe COPD. Percent truncal fat (truncal obesity) did not affect functional
      performance directly, but did affect it indirectly through dyspnea. The 6-min
      walk test distance, dyspnea, and DLCO accounted for 29% of the variability in
      functional performance. CONCLUSIONS: We believe that the effectiveness of
      pulmonary rehabilitation will be enhanced when nurses consider weight loss as a
      controllable factor for overweight and obese clients. The increasing prevalence
      of obesity in this population may dictate collaboration between dieticians and
      pulmonary rehabilitation nurses for effective rehabilitation programs. CLINICAL
      RELEVANCE: These findings suggest that percent truncal fat (truncal obesity) may
      be an indirect factor in the performance of daily activities of people with COPD.
      We anticipate that clinicians will use knowledge derived from this study to
      develop interventions to reduce or minimize truncal fat (truncal obesity) and its
      effects on people with COPD.

PMID- 22882560
TI  - Mass administration of the antimalarial drug mefloquine to Guantanamo detainees:
      a critical analysis.
AB  - Recently, evidence has emerged from an unusual form of mass drug administration
      practised among detainees held at US Naval Station Guantanamo Bay, Cuba
      ('Guantanamo'), ostensibly as a public health measure. Mefloquine, an
      antimalarial drug originally developed by the US military, whose use is
      associated with a range of severe neuropsychiatric adverse effects, was
      administered at treatment doses to detainees immediately upon their arrival at
      Guantanamo, prior to laboratory testing for malaria and irrespective of symptoms
      of disease. In this analysis, the history of mefloquine's development is reviewed
      and the indications for its administration at treatment doses are discussed. The
      stated rationale for the use of mefloquine among Guantanamo detainees is then
      evaluated in the context of accepted forms of population-based malaria control.
      It is concluded that there was no plausible public health indication for the use
      of mefloquine at Guantanamo and that based on prevailing standards of care, the
      clinical indications for its use are decidedly unclear. This analysis suggests
      the troubling possibility that the use of mefloquine at Guantanamo may have been
      motivated in part by knowledge of the drug's adverse effects, and points to a
      critical need for further investigation to resolve unanswered questions regarding
      the drug's potentially inappropriate use.

PMID- 22882561
TI  - Pitted keratolysis; physicians' treatment and their perceptions in Dutch army
      personnel.
AB  - BACKGROUND: Pitted keratolysis (PK) is a common plantar skin manifestation in
      army personnel, farmers and athletes. Due to pain while walking and marching, the
      condition can cause reduced operational deployability (in case of army
      personnel). OBJECTIVE: We used a questionnaire to investigate currently used
      treatment options of PK and perceptions on perceived efficacy of these treatments
      among Royal Netherlands Armed Forces primary health care physicians. METHODS: A
      cross-sectional anonymous postal questionnaire survey was conducted among all
      Royal Netherlands Armed Forces primary health care physicians. In addition to
      question about prescription behaviour on the treatment of PK by topical and oral
      therapies and given non-pharmacological treatment, several questions assessed
      perceived efficacy of these therapies. RESULTS: Of the 164 eligible primary
      health care physicians, 51 (31.1%) completed the questionnaire. Half of
      physicians had seen less than five patients with PK in the preceding year. Two
      thirds of physicians reported problems with operational deployability in less
      than 10% of army personnel with PK. PK was treated mostly with topical and non
      pharmacological treatments. Oral therapy was seldom prescribed. For
      hyperhidrosis, aluminium chloride hexahydrate was used in most cases. CONCLUSION:
      PK and related reduced operational deployability were less often reported than
      expected in this study. Dutch physicians prefer combined topical antibiotic
      therapy with non-pharmacological treatments and perceive the efficacy of topical
      antibiotic therapy superior to non-pharmacological treatments. Preventive
      measures, topical antibiotic therapy and adequate treatment of hyperhidrosis are
      the mainstay methods in the management of patients with PK.

PMID- 22882563
TI  - Associations between health  insurance and generalized  periodontal disease in a
      study  population of Gullah African  Americans with type-2 diabetes.
AB  - OBJECTIVES: To explore the relationship between health insurance status
      (Medicare, Medicaid, private, and uninsured) and generalized periodontal disease
      (GPD) among a study population (N = 245) of adult Gullah African Americans with
      type-2 diabetes mellitus (T2DM) ages <65 years. METHODS: We used multivariable
      logistic regression to assess GPD [using three different and increasingly severe
      clinical assessments: 3, 4, and 5 mm clinical attachment level (CAL) at 30% of
      sites] according to health insurance status. RESULTS: Prevalence of GPD was
      33.06% for 3, 18.78% for 4, and 9.80% for 5 mm CAL. Age ranged 26-64 years (mean
      = 52.11, SD = 8.53, median = 53). Private insurance was most prevalent (39.59%),
      followed by uninsured (30.61%), Medicaid (16.33%), and Medicare (13.47%). Results
      showed increased odds (versus private insurance) for GPD at 3 mm among Medicaid
      (OR = 1.82, P = 0.2404), Medicare (OR = 3.34, P = 0.0103), and uninsured (OR =
      1.96, P = 0.0956) groups; GPD at 4 mm among Medicaid (OR = 1.97, P = 0.3303),
      Medicare (OR = 5.02, P = 0.0121), and uninsured (OR = 3.38, P = 0.0319) groups;
      and GPD at 5 mm among Medicaid (OR = 1.21, P = 0.8507), Medicare (OR = 12.62, P =
      0.0038), and uninsured (OR = 4.00, P = 0.0763) groups. CONCLUSIONS: We observed
      substantial disparities for GPD severity among those without private health
      insurance even after adjusting for glycemic control, income, dental health
      behaviors, and other covariates. Improved insurance benefits as well as
      individualized oral health educational interventions may decrease GPD severity
      for this study population of younger (ages <65 years) Gullah African Americans
      with T2DM, particularly those with Medicare insurance.

PMID- 22882562
TI  - Hybrid porphyrin-silicon nanowire field-effect transistor by opto-electrical
      excitation.
AB  - A porphyrin-silicon nanowire (Si-NW) hybrid field-effect transistor is
      introduced. The hybrid device has separate electrical and optical gates
      surrounding the Si-NW channel. Porphyrin, a component of chlorophyll, is employed
      as an optical gate to modulate the potential of the Si-NW channel. Due to the
      independently formed hybrid gates, both optical and electrical excitation can
      effectively modulate the device. The exposed porphyrin optical gate responds to
      the optical excitation, and independently formed electrical gates respond to the
      electrical excitation. Charge transfer characteristics between a semiconductor
      channel and the porphyrin optical gate are deeply investigated. Optical,
      electrical, and opto-electrical excitation methods are employed to analyze the
      charging and discharging behaviors. Of these methods, opto-electrical excitation
      enables the strongest charge transfer because the inversion electron formation by
      an electrical pulse and the photoinduced charge transfer by an optical stimulus
      are affected simultaneously. Discharging processes, such as rapid discharging,
      exponential detrapping, and the formation of metastable states are also analyzed.

PMID- 22882564
TI  - The growth of the canine glioblastoma cell line D-GBM and the canine histiocytic
      sarcoma cell line DH82 is inhibited by the resveratrol oligomers hopeaphenol and
      r2-viniferin.
AB  - Vineatrol((r)) 30 is a grapevine-shoot extract, which contains resveratrol as
      well as considerable amounts of so-called resveratrol oligomers such as
      hopeaphenol and r2-viniferin. In this study, we analysed whether the two above
      mentioned resveratrol oligomers were able to inhibit the growth of the canine
      glioblastoma cell line D-GBM and the canine histiocytic sarcoma cell line DH82,
      compared their potency to inhibit tumour cell growth with that of resveratrol and
      determined whether the induction of apoptosis via caspase 9 and 3/7 activation
      underlies the tumour cell growth-inhibiting effect of hopeaphenol and r2
      viniferin. Vineatrol((r)) 30, resveratrol, hopeaphenol and r2-viniferin inhibited
      the growth of D-GBM and DH82 cells in a concentration-dependent manner, whereby
      hopeaphenol and r2-viniferin were more potent than resveratrol itself in
      inhibiting the growth of the canine tumour cell lines. Moreover, the anti
      proliferative effect of both resveratrol oligomers in D-GBM cells is based on
      their capacity to induce caspase 9 and 3/7 activation. 

PMID- 22882565
TI  - Tight junction properties change during epidermis development.
AB  - In terrestrial animals, the epidermal barrier transitions from covering an
      organism suspended in a liquid environment in utero, to protecting a terrestrial
      animal postnatally from air and environmental exposure. Tight junctions (TJ) are
      essential for establishing the epidermal permeability barrier during embryonic
      development and modulate normal epidermal development and barrier functions
      postnatally. We now report that TJ function, as well as claudin-1 and occludin
      expression, change in parallel during late epidermal development. Specifically,
      TJ block the paracellular movement of Lanthanum (La(3+)) early in rat in vivo
      prenatal epidermal development, at gestational days 18-19, with concurrent
      upregulation of claudin-1 and occludin. TJ then become more permeable to ions and
      water as the fetus approaches parturition, concomitant with development of the
      lipid epidermal permeability barrier, at days 20-21. This sequence is
      recapitulated in cultured human epidermal equivalents (HEE), as assessed both by
      ultrastructural studies comparing permeation of large and small molecules and by
      the standard electrophysiologic parameter of resistance (R), suggesting further
      that this pattern of development is intrinsic to mammalian epidermal development.
      These findings demonstrate that the role of TJ changes during epidermal
      development, and further suggest that the TJ-based and lipid-based epidermal
      permeability barriers are interdependent.

PMID- 22882566
TI  - Vibrio cholerae/mimicus in fecal microbiota of healthy children in a cholera
      endemic urban slum setting in Kolkata, India.
AB  - During a double-blind, randomized, placebo-controlled probiotic trial among 3758
      children residing in an urban slum in Kolkata, India, Vibrio cholerae/mimicus was
      detected in fecal microbiota of healthy children. The importance of this finding
      in the local, regional and global transmission of cholera is discussed.

PMID- 22882567
TI  - The +252A/G polymorphism in the lymphotoxin-alpha gene increases the risk of
      asthma: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: A number of studies have shown that the +252A/G
      polymorphism (rs909253) in the lymphotoxin-alpha (LT-alpha) gene is implicated in
      susceptibility to asthma. However, the findings have been inconclusive. The aim
      of this study was to investigate the association between the +252A/G polymorphism
      in the LT-alpha gene and the risk of asthma by performing a meta-analysis.
      METHODS: The Pubmed and Embase databases were searched for all studies relating
      to this polymorphism and the risk of asthma. Statistical analyses were performed
      using the Revman4.2 and STATA 10.0 software. RESULTS: Thirteen case-control
      studies that included a total of 2220 cases and 6428 controls were included in
      the meta-analysis. There was no significant association between this polymorphism
      and the risk of asthma in the all-combined analysis (odds ratio (OR) 1.14, 95%
      confidence interval (CI): 0.89-1.45 for GG+GA vs AA). In a subgroup analysis by
      ethnicity, no significant association with asthma risk was identified in Asians
      (OR 1.31, 95% CI: 0.97-1.77) or Europeans (OR 1.08, 95% CI: 0.77-1.53). In a
      subgroup analysis by age, a significantly increased risk was identified among
      adults (OR 1.25, 95% CI: 1.03-1.50) but not children (OR 1.04, 95% CI: 0.28
      3.89). In a subgroup analysis by atopic status, a significantly elevated risk was
      identified among atopic (OR 1.55, 95% CI: 1.28-1.87) but not non-atopic
      individuals (OR 0.94, 95% CI: 0.53-1.68). CONCLUSIONS: This meta-analysis
      suggested that the +252A/G polymorphism in the LT-alpha gene is a risk factor for
      asthma in adults and atopic populations.

PMID- 22882568
TI  - The association of osteopontin and LMX1A expression with World Health
      Organization grade in meningiomas and gliomas.
AB  - AIMS: Osteopontin (OPN) and LIM homeobox transcription factor 1, alpha (LMX1A)
      are important factors related to tumour progression, invasion and metastasis in
      human cancers. The aim of this study was to test the hypothesis that expression
      of OPN and of LMX1A correlate with the World Health Organization (WHO) grading
      system of primary brain tumours. METHODS AND RESULTS: Immunohistochemical
      analyses of OPN and LMX1A expression were performed in 139 cases of brain tumour,
      including 65 meningiomas, 71 gliomas, and three central neurocytomas. More than
      90% of WHO grade I meningiomas showed negative or weak staining for OPN and
      LMX1A. However, among all WHO grade II and III meningiomas, 100% and 66.7% showed
      moderate or strong staining for OPN and LMX1A, respectively. Similarly, higher
      percentages of WHO grade I and II gliomas than of WHO grade III and IV gliomas
      showed negative or weak staining for OPN. A higher intensity of immunoreactivity
      for LMX1A correlated with more advanced grade in WHO grade I-III gliomas, but not
      in WHO grade IV tumours. CONCLUSIONS: Higher immunostaining intensity for OPN and
      LMX1A correlated with WHO grades for meningiomas and some gliomas. Contrary to
      our expectations, LMX1A staining in WHO grade IV gliomas was shown to be weaker
      than in WHO grade III tumours.

PMID- 22882569
TI  - Effects of selenium status, dietary glucosinolate intake and serum glutathione S
      transferase alpha activity on the risk of benign prostatic hyperplasia.
AB  - Study Type--Prognosis (case control) Level of Evidence 2. What's known on the
      subject? and What does the study add? Geographical and ethnic differences in the
      distribution of BPH and the results of migrant studies indicate that not only
      age, androgens and genetics, but also modifiable factors may play a role in the
      aetiology of BPH. Oxidative stress induced by chronic inflammation could be a
      cause and antioxidants, including selenoproteins, may reduce the risk. The
      published data related to this topic are scarce and are mainly based on cross
      sectional and case-control studies. In a nested case-control study, we observed a
      significant inverse association between serum selenium concentrations and the
      risk of BPH. These results need to be confirmed in larger, prospective
      epidemiological studies. Prostate enlargement is an increasing health problem as
      a result of an ageing population in many countries. Modifiable factors may also
      play a role. In the present study, before this antioxidant can be recommended as
      a preventive measure. OBJECTIVE: * To determine whether geographical differences
      in the distribution of benign prostatic hyperplasia (BPH) and migrant studies
      indicate that modifiable factors play a role in the aetiology of BPH. Oxidative
      stress produced by chronic inflammation could represent one of the causes, and
      antioxidants, including selenoproteins, may reduce the risk. SUBJECTS AND
      METHODS: * Conditional logistic regression was used to examine the associations
      of serum selenium and selenoprotein P concentrations and glutathione peroxidase
      activity with respect to the risk of BPH in a case-control study nested in the
      European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort,
      including 111 cases and 214 matched controls. * In addition, dietary
      glucosinolate intake and the serum glutathione S-transferase alpha concentration
      was investigated. RESULTS: * The risk of BPH significantly decreased with an
      increasing serum selenium concentration; the risk estimate was 0.83 (35% CI 0.69
      0.99) per 10 ug/L increase in serum selenium concentration. * However, no
      significant association was present for serum selenoprotein P concentration or
      glutathione peroxidase activity. Risk estimates for BPH decreased with a higher
      intake of glucosinolates, although the results were not statistically
      significant. CONCLUSION: * A low serum selenium concentration may increase the
      risk of BPH, although the findings reported in the present study need to be
      confirmed in larger, well-designed epidemiological studies.

PMID- 22882570
TI  - Nitric oxide and endothelin-1 release after one-lung ventilation during
      thoracoabdominal esophagectomy.
AB  - One-lung ventilation (OLV) is applied during esophagectomy to improve exposure
      during the thoracic part of the operation. Collapse of lung tissue, shunting of
      pulmonary blood flow, and changes in alveolar oxygenation during and after OLV
      may possibly induce an ischemia-reperfusion response in the lung, which may
      affect the pulmonary endothelium. Such a reaction might thereby contribute to the
      frequently occurring respiratory complications among these patients. In this
      small trial, 30 patients were randomized to either OLV (n= 16) or two-lung
      ventilation (TLV, n= 14) during esophagectomy. Central venous and arterial plasma
      samples were taken before and after OLV/TLV for analysis of nitrite and a
      metabolite of nitric oxide (NO), and also during the 1st, 2nd, 3rd, and 10th
      postoperative day for analysis of endothelin, another endothelium-derived
      vasoactive mediator. Lung biopsies were taken before and after OLV or TLV, and
      analyzed regarding immunofluorescence for isoform of NO synthase, a protein
      upregulated during inflammatory response and also vascular congestion. No changes
      in lung isoform of NO synthase immunofluorescence or vascular congestion were
      registered after neither OLV nor TLV. Plasma nitrite and endothelin levels were
      similar in the two study groups. We conclude that OLV does not seem to have any
      influence on key regulators of pulmonary vascular tone and inflammation, i.e. NO
      and endothelin. From this perspective, OLV seems to be a safe method, which
      defends its clinical position to facilitate surgical exposure during
      thoracoabdominal esophagectomy. 

PMID- 22882571
TI  - A possible biomechanical role of occlusal cusp-fossa contact relationships.
AB  - Biomechanical features of occlusal contacts are important in understanding the
      role of the occlusion contributing to masticatory function. Cusp-fossa contact is
      the typical pattern of occlusion between upper and lower teeth. This includes
      static relations, such as that during clenching, and dynamic relations when
      mandibular teeth contact in function along the maxillary occlusal pathways, as
      during mastication. During clenching in the maximum intercuspal position (ICP),
      cuspal inclines may take the role of distributing the occlusal forces in multi
      directions thus preventing excessive point pressures on the individual tooth
      involved. During chewing movement on the functional side, the mandible moves
      slightly from buccal through the maximum ICP to the contralateral side. The part
      of the chewing cycle where occlusal contacts occur and the pathways taken by the
      mandible with teeth in occlusal contacts are determined by the morphology of the
      teeth. The degree of contact is associated with the activity of the jaw muscles.
      To obtain repeatable static and dynamic occlusal contact information provided by
      the morphology of the teeth, maximum voluntary clenching and chewing movements
      with maximum range are needed. In conclusion, in addition to the standard
      occlusal concepts of centric relation/centric occlusion and group function/cuspid
      protection relation, biomechanics in static and dynamic cusp-fossa relationships
      should be included to develop an understanding of occlusal harmony which includes
      no interfering or deflective contacts in functional occlusal contact.

PMID- 22882572
TI  - Feasibility of early discharge after implantable cardioverter-defibrillator
      procedures.
AB  - INTRODUCTION: Registry data demonstrate considerably low complication rates after
      implantable cardioverter-defibrillator (ICD) procedures for primary prevention of
      sudden death. Yet standard of care includes postimplant overnight in-hospital
      observation that may levy substantial unnecessary financial burden on health care
      systems. In appropriate patients, discharge soon after implant could translate
      into significant cost savings, if such practice does not result in complications.
      We applied a simple clinical algorithm to assess feasibility of discharge on the
      same day of ICD implantation in patients at low risk for procedural
      complications. METHODS: We prospectively randomized primary prevention ICD
      candidates at low risk for complications (not pacing-dependent or requiring
      bridging heparin anticoagulation) to next-day discharge with overnight in
      hospital observation, or same-day discharge with remote monitoring for 24 hours
      after ICD implant. Implants were performed via cephalic vein access, and
      randomization occurred after 4-hours clinical observation and device
      interrogation. All patients were followed for a minimum of 6 weeks to assess
      acute procedural complications. RESULTS: 71 patients comprised the study cohort
      (mean age 62, 79% male) after 3 were excluded. The most common indication for ICD
      implant was ischemic cardiomyopathy with ejection fraction <=35%. Device data
      obtained through 24-hour remote monitoring was comparable to 4-hour postimplant
      parameters in same-day discharge patients. No acute complications occurred in
      same-day discharge patients; 1 next-day discharge patient developed pneumothorax.
      CONCLUSION: ICD implantation with same-day discharge is reasonable in patients at
      low risk for complications. Remote monitoring can be useful in indicating lead
      parameter stability during the immediate postoperative period.

PMID- 22882573
TI  - Intraclonal diversity of the Pseudomonas aeruginosa cystic fibrosis airway
      isolates TBCF10839 and TBCF121838: distinct signatures of transcriptome,
      proteome, metabolome, adherence and pathogenicity despite an almost identical
      genome sequence.
AB  - Microevolution of closely related Pseudomonas aeruginosa was compared in the
      clone TB strains TBCF10839 and TBCF121838 which had been isolated from two
      unrelated individuals with cystic fibrosis who had acquired clone TB during a
      local outbreak. Compared with the strain PAO1 reference sequence the two clone TB
      genomes shared 23 155 nucleotide exchanges, 32 out-of-frame indels in the coding
      region and another repertoire of replacement and genomic islands such as PAGI-1,
      PAGI-2, PAGI-5, LESGI-1 and LES-prophage 4. Only TBCF121838 carried a genomic
      island known from Ralstonia pickettii. Six of the seven strain-specific sequence
      variations in the core genome were detected in genes affecting motility, biofilm
      formation or virulence, i.e. non-synonymous nucleotide substitutions in mexS,
      PA3729, PA5017, mifR, a frameshift mutation in pilF (TBCF121838) and an
      intragenic deletion in pilQ (TBCF10839). Despite their almost identical genome
      sequence the two strains differed strongly from each other in transcriptome and
      metabolome profiles, mucin adherence and phagocytosis assays. TBCF121838 was
      susceptible to killing by neutrophils, but TBCF10839 could grow in leucocytes.
      Microevolution in P. aeruginosa apparently can generate novel complex traits by
      few or even single mutations provided that predisposing mutational events had
      occurred before in the clonal lineage.

PMID- 22882574
TI  - Buccal bone plate in immediately placed and restored implant with Bio-Oss((r))
      collagen graft: a 1-year follow-up study.
AB  - OBJECTIVES: The aim of this study was to radiographically assess the vertical and
      horizontal alterations of buccal alveolar bone after the insertion of a post
      extractive implant using Bio-Oss((r)) Collagen graft. MATERIAL AND METHODS: The
      study was designed as a prospective study. Adult patients were eligible for the
      study if they needed one or more immediately inserted and immediately restored
      implant replacing teeth to be extracted within region 15-25. After the insertion,
      the buccal gap was carefully grafted using Bio-Oss((r)) Collagen and the implant
      immediately restored. Cone-Beam Computed Tomography (CBCT) was performed
      immediately after surgery and a series of measurements were made to determine the
      dimension of the buccal bone plate and the void between implant and extraction
      socket. A second CBCT was taken and the measurements repeated after 12 months.
      RESULTS: Altogether, 69 patients were included in the study; a total of 69
      implants were inserted. The study demonstrated that the extraction of a tooth and
      the immediate insertion of an implant together with an xenograft resulted in
      alterations of the vertical and horizontal dimension of the buccal bone plate
      (respectively, 25.6% and 29.3%). Nevertheless, the vertical and horizontal gap
      reduction was nearly complete (respectively, 99.3% and 99.1%) and the implant was
      normally in contact with buccal bone. CONCLUSIONS: Implant placement into
      extraction sockets can result in favorable radiological results even in the
      presence of evident alterations of the buccal bone wall.

PMID- 22882575
TI  - Efficacy of intraoperative antiseptic scrub after nail removal surgery.

PMID- 22882576
TI  - Anaesthesia with medetomidine, midazolam and ketamine in six gorillas after
      premedication with oral zuclopenthixol dihydrochloride.
AB  - OBJECTIVE: To evaluate the effects of medetomidine, midazolam and ketamine (MMK)
      in captive gorillas after premedication with oral zuclopenthixol. STUDY DESIGN:
      Case series. ANIMALS: Six gorillas, two males and four females, aged 9-52 years
      and weighing 63-155 kg. METHODS: The gorillas were given zuclopenthixol
      dihydrochloride 0.2 +/- 0.05 mg kg(-1) per os twice daily for 3 days for
      premedication. On the day of anaesthesia the dose of zuclopenthixol was increased
      to 0.27 mg kg(-1) and given once early in the morning. Anaesthesia was induced
      with medetomidine 0.04 +/- 0.004 mg kg(-1) , midazolam 0.048 +/- 0.003 mg kg(-1)
      and ketamine 4.9 +/- 0.4 mg kg(-1) intramuscularly (IM). Upon recumbency, the
      trachea was intubated and anaesthesia was maintained on 1-2% isoflurane in
      oxygen. Physiological parameters were monitored every 10 minutes and arterial
      blood gas analysis was performed once 30-50 minutes after initial darting. At the
      end of the procedure, 42-115 minutes after initial darting, immobilisation was
      antagonized with atipamezole 0.21 +/- 0.03 mg kg(-1) and sarmazenil 5 +/- 0.4 MUg
      kg(-1) IM. RESULTS: Recumbency was reached within 10 minutes in five out of six
      animals. One animal required two additional darts before intubation was feasible.
      Heart rate ranged from 60 to 85 beats minute(-1) , respiratory rate from 17 to 46
      breaths minute(-1) and temperature from 36.9 to 38.3  degrees C. No spontaneous
      recoveries were observed and anaesthetic level was stable. Blood gas analyses
      revealed mild respiratory acidosis, and mean PaO(2) was 24.87 +/- 17.16 kPa (187
      +/- 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was
      smooth and gorillas were sitting within 25 minutes. CONCLUSION AND CLINICAL
      RELEVANCE: The drug combination proved to be effective in anaesthetizing captive
      gorillas of various ages and both sexes, with minimal cardio-respiratory changes.

PMID- 22882577
TI  - Impact on storage quality of red blood cells and platelets by ultrahigh-frequency
      radiofrequency identification tags.
AB  - BACKGROUND: Compared to ISBT128 code labels, radiofrequency identification (RFID)
      tags have incomparable advantages and gradually applied in blood management
      system. However, there is no global standard for the uses of RFID frequency. Even
      though ISBT recommended high-frequency RFID with 13.56MHz, 820- to 960-MHz
      ultrahigh frequency (UHF) RFID technology in many ways has even more advantages.
      For this reason, we studied the effect of UHF RFID tags with 820- to 960-MHz
      exposure on storage quality of red blood cells (RBCs) and platelets (PLTs). STUDY
      DESIGN AND METHODS: Thirty units of collected and prepared suspended RBCs (sRBCs)
      and PLTs were divided into two bags, one each for the test and control groups.
      The sRBCs were stored in 4+/-2 degrees C refrigerator and the PLTs in a 22+/-2
      degrees C rocking box. The test groups were exposed to RF reader continuously
      during storage. Sampling at different time points and biologic changes were
      tested. RESULTS: As the extension of storage and the pH and chlorine levels in
      the supernatant of sRBCs were reduced, free hemoglobin, potassium, and sodium
      increased, but were not significant between test and control groups (p>0.05).
      During the storage period, the pH levels, PLT count, and PLT aggregation rate
      were decreased in both test and control groups, but were not significant
      (p>0.05). CONCLUSION: When exposed to 820- to 960-MHz RF, the biologic and
      biochemical indexes are not found to be exacerbated during 35 days of storage for
      sRBCs and 5 days for PLTs, respectively.

PMID- 22882578
TI  - Acute Surgical Unit at Auckland City Hospital: a descriptive analysis.
AB  - Lack of timely assessment and access to acute operating rooms is a worldwide
      problem and also exists in New Zealand hospitals. To address these issues, an
      Acute Surgical Unit (ASU) was set up at Auckland City Hospital (ACH) in January
      2009. This service has evolved and been modified to address the specific needs of
      acute surgical patients of ACH. Despite initial challenges inherent to setting up
      a new service, the Unit has been in steady operation and enhanced its performance
      over time. This paper is a descriptive analysis of the design of the ACH ASU and
      discusses some of the indications for streamlining acute surgical services at a
      large tertiary metropolitan hospital in New Zealand. Performance of the ASU has
      shown benefits for acute patients and the Hospital. The acute surgical rotation
      has also been beneficial for surgical training.

PMID- 22882579
TI  - Efficacy comparison between simple mixed-dilution and simple mid-dilution on-line
      hemodiafiltration techniques: a crossover study.
AB  - Mid-dilution and mixed-dilution on-line hemodiafiltration (OL-HDF) techniques are
      innovated to overcome the limitations of two standard techniques including
      predilution and postdilution. Unfortunately, the head-to-head comparisons between
      these two novel techniques in the same study are still limited. Moreover, the
      original mid-dilution and mixed-dilution OL-HDF need special dialyzers and
      special machines. In the present study, simple mid-dilution and simple mixed
      dilution OL-HDF were settled with the aim for clinical use in general
      hemodialysis (HD) centers. The efficacies of uremic toxins removal between both
      modalities were measured and compared. This prospective randomized crossover
      study was conducted on 12 stable HD patients undergoing simple mixed-dilution and
      simple mid-dilution OL-HDF techniques. HD prescriptions were similar in both
      techniques. The dialysis efficacies were determined by calculating small- (urea,
      creatinine, and phosphate) and middle-molecule (beta-2 microglobulin [beta2M])
      removal. Moreover, potential complications such as high transmembrane pressure
      (TMP) and protein loss were also observed. Simple mixed-dilution OL-HDF provided
      significantly greater clearances of urea, creatinine, and beta2M when compared
      with the simple mid-dilution OL-HDF techniques. Phosphate clearances in both
      techniques were comparable. In addition, TMP and dialysate albumin loss were not
      different. There were no intradialytic complications in both techniques. Simple
      mixed-dilution OL-HDF could provide greater efficacy for small- and middle
      molecule clearances and acceptable potential risks, while phosphate removal is
      comparable.

PMID- 22882580
TI  - Inference of the Basal epithelial phenotype in breast carcinoma from differential
      marker expression, using tissue microarrays in triple negative breast cancer and
      women younger than 35.
AB  - Basal-cell phenotype breast carcinoma has been associated with high-grade and
      metaplastic morphology, expression of basal-type cytokeratins, uniform negativity
      for ER and HER2, and decreased overall survival. Breast cancers occurring in
      young women are usually T2 disease at presentation, high-grade and of poor
      prognosis. We compared two groups of breast cancers, (a) ER-, PR-, HER2- (triple
      negative) [TNBrCa] and (b) non-triple negative breast cancers (non-TNBrCa)
      occurring in women under 35, using tissue microarray technology to characterize
      expression of the basal/myoepithelial cytokeratins (CK5/6, CK7, and CK14),
      luminal cytokeratins (CK8, CK18, and CK19), EGFR, p-cadherin, c-kit, p63, and
      p53. We also sought to identify characteristic histomorphologic features
      indicative of basal-like phenotype. The triple negative group showed preferential
      staining versus the age <35 group for CK5/6 (22% versus 4% p = 0.05), CK14 (44%
      versus 15%, p = 0.013), EGFR (83% versus 24%, p < 0.0001) and c-kit (19% versus
      0% p = 0.026). Conversely, non-TNBrCa in women younger than 35 demonstrated
      increased expression of the luminal CK8 (92% versus 60%) compared with the triple
      negative patients (p = 0.006). The TNBrCa have characteristic histologic features
      including higher tumor grade, pushing tumor border, geographic necrosis,
      syncytial growth pattern, brisk mitotic activity, lack of/minimal in situ
      component, medullary-like and metaplastic differentiation. Invasive carcinomas in
      women younger than 35 usually have an associated in situ component, prominent
      nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple
      negativity for ER/PR/HER2 coupled with EGFR, c-kit, and basal/myoepithelial
      cytokeratins (CK5/6, CK14) expression, and distinctive histomorphologic features
      predict morphology consistent with basal-cell phenotype.

PMID- 22882581
TI  - Racial disparity in oral and pharyngeal cancer in Florida in 1991-2008: mixed
      trends in stage of diagnosis.
AB  - OBJECTIVES: To explore changes in distribution of stage at diagnosis among
      individuals with oral and pharyngeal cancers over the past two decades and
      whether the changes differ by race. METHODS: We obtained 1991-2008 cancer
      incidence data for nine anatomic sites of the oral and pharyngeal structure from
      the Florida Cancer Data System. These cancers were grouped into oral squamous
      cell carcinoma (SCC), pharyngeal SCC, and other head and neck cancers. Annual
      percent change was calculated for each group to characterize trends in age
      adjusted cancer incidence over time by race and stage at diagnosis. RESULTS:
      During 1991-2008, the overall age-adjusted oral SCC incidence was decreasing for
      both races, with a greater decline observed among Blacks. There was a large drop
      in incidence of regional-stage diagnoses among Blacks. For pharyngeal SCC, the
      age-adjusted incidence of localized- and regional-stage diagnoses was increasing
      for Whites during 1991-2008, with the largest increase in the incidence of
      regional-stage diagnoses. The percentage of localized-stage diagnoses was
      increasing for both races for oral SCC. A slight increase in percentage of
      localized-stage diagnoses was observed for Blacks for pharyngeal SCC, whereas no
      obvious change was observed among Whites. CONCLUSIONS: Blacks continued to have
      lower percentages of localized-stage diagnoses than Whites for nearly all sites,
      but an increasing percentage of localized-stage diagnoses was observed for oral
      SCC among Blacks. For pharyngeal SCC, the increase in incidence among Whites was
      accompanied by an increasing percentage of late-stage diagnoses. Coordinated
      public health approaches with a special emphasis on screening underserved
      populations are needed.

PMID- 22882582
TI  - A randomized double-blinded placebo-controlled study to evaluate an effective
      ciclosporin dose for the treatment of feline hypersensitivity dermatitis.
AB  - BACKGROUND: Hypersensitivity dermatitides (HD) are frequently suspected in cats,
      but there are few clinical studies on safe and effective treatments in the
      published literature. OBJECTIVES: To establish a safe and effective dose of
      ciclosporin in the treatment of feline HD. ANIMALS: One hundred client-owned cats
      with feline HD. METHODS: Double-blind study, with cats randomly assigned to
      receive ciclosporin at either 7.0 mg/kg once daily (n = 33) or 2.5 mg/kg once
      daily (n = 32) or a placebo (n = 35) for 6 weeks. RESULTS: Mean Total Lesion
      Scores with 7.0 mg/kg ciclosporin were significantly lower than with 2.5 mg/kg
      ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total
      Lesion Scores improved by >50% in 70% of the 7.0 mg/kg group, compared with 47%
      in the 2.5 mg/kg group and 23% in the placebo group (P = 0.0006). The
      investigators' Global Assessment of Improvement was 'excellent' or 'good' in 61%
      of cats treated with 7.0 mg/kg ciclosporin, compared with 47% of cats given 2.5
      mg/kg and 23% given placebo. The improvement in Investigator Pruritus Scores was
      significantly greater in cats treated with 7.0 mg/kg ciclosporin (54%) compared
      with both 2.5 mg/kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063).
      Mild gastrointestinal disorders were the most common adverse events, but these
      did not require cessation of therapy. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Results suggest that 7.0 mg/kg ciclosporin once daily in food or per os for 6
      weeks is effective and well tolerated in feline HD.

PMID- 22882583
TI  - Morphological features of coronary arteries and lesions in hearts from five
      species of sharks collected from the northwestern Atlantic Ocean.
AB  - Morphological features of coronary arteries and incidental lesions are reported
      from hearts in five species of sharks, the shortfin mako shark, Isurus
      oxyrhinchus Rafinesque, thresher shark Alopias vulpinus (Bonaterre), blue shark,
      Prionace glauca L., the smooth dogfish, Mustelus canis (Mitchill), and spiny
      dogfish, Squalus acanthias L. Sharks were collected from the northwestern
      Atlantic between June and August from 1996 to 2010. They were necropsied dockside
      and the hearts were preserved in buffered formalin. Routine sections including
      ventricle/conus arteriosus and the atrio-ventricular junctions were embedded in
      paraffin, stained with common histological and immunohistochemical methods and
      examined by brightfield microscopy. Myointimal hyperplasia, medial myo-myxomatous
      hyperplasia and bifurcation pads were observed commonly, and medial muscle
      reorientation and epicardial myeloid tissues were rare. All the above features
      differed in severity, prevalence and distribution depending on anatomical site
      and shark species/size. Morphometric analysis indicated that myomyxomatous
      hyperplasia is associated with luminal narrowing of blood vessels. As suggested
      previously, the described morphological features are most likely physiological
      responses to blood flow characteristics. Vascular and cardiac lesions were
      uncommon and included, granulomatous proliferative epicarditis with
      fibroepitheliomas, myxomatous epicardial expansions, medial arterial vacuolation,
      myocardial fibrosis, acute ventricular emboli and parasitic granulomas. The
      lesions of embolism, proliferative and granulomatous epicarditis and myocardial
      fibrosis were in all sharks associated with capture events including retained
      fishing hooks. The significance and aetiopathogenesis of medial vacuolation and
      epicardial myxomatous expansions remains unclear.

PMID- 22882584
TI  - Temperature response of carbon isotope discrimination and mesophyll conductance
      in tobacco.
AB  - The partial pressure of CO2 at the sites of carboxylation within chloroplasts
      depends on the conductance to CO2 diffusion from intercellular airspace to the
      sites of carboxylation, termed mesophyll conductance (gm ). We investigated the
      temperature response of gm in tobacco (Nicotiana tabacum) by combining gas
      exchange in high light, ambient CO2 in either 2 or 21% O2 with carbon isotope
      measurements using tuneable diode laser spectroscopy. The gm increased linearly
      with temperature in 2 or 21% O2 . In 21% O2 , isotope discrimination associated
      with gm decreased from 5.0 +/- 0.2 to 1.8 +/- 0.20/00 as temperature increased
      from 15 to 40  degrees C, but the photorespiratory contribution to the isotopic
      signal is significant. While the fractionation factor for photorespiration (f =
      16.2 +/- 0.70/00) was independent of temperature between 20 and 35  degrees C,
      discrimination associated with photorespiration increased from 1.1 +/- 0.01 to
      2.7 +/- 0.020/00 from 15 to 40  degrees C. Other mitochondrial respiration
      contributed around 0.2 +/- 0.030/00. The drawdown in CO2 partial pressure from
      ambient air to intercellular airspaces was nearly independent of leaf
      temperature. By contrast, the increase in gm with increasing leaf temperature
      resulted in the drawdown in CO2 partial pressure between intercellular airspaces
      and the sites of carboxylation decreasing substantially at high temperature.

PMID- 22882585
TI  - Five tips on getting research published.

PMID- 22882586
TI  - Geriatric dentistry: is rethinking still required? A community-based survey in
      Indian population.
AB  - BACKGROUND: India has a large geriatric population (60 years and above) of 77
      million; comprising 7.7% of its total population. Poor oral health and loss of
      teeth not only adversely affect the dietary intake and nutritional status and
      thereby compromise general health, but can also deny them the pleasure of eating
      food of their choice. OBJECTIVE: To assess the level of edentulousness, denture
      wearing and denture needs of the elderly in the community and to study the
      correlation between oral health parameters and sociodemographic variables which
      would help us to define better treatment modalities, counselling and thus improve
      the oral health of our geriatric patients. MATERIALS AND METHODS: Subjects who
      were 60 years and above were considered for this study and were randomly
      selected. Of the 1360 elderly who were enrolled in the study, 780 (57.35%) were
      males and 580 (42.64%) were female. This sample size is in proportion to the
      total population for the pilot study. They were given an oral examination and a
      questionnaire. RESULTS: Fifty seven percent (57%) of the elderly were not
      satisfied with their oral health status and function. CONCLUSION: Complete
      edentulousness of both the arches was highest in the middle socio-economic group,
      and was the lowest in the low socio-economic group. Less than 50% of edentulous
      elderly and only 10% of partially edentulous elderly were wearing dentures.

PMID- 22882587
TI  - Influence of hypercapnia on the synthesis of neuropeptides and their receptors in
      murine brain.
AB  - BACKGROUND AND OBJECTIVE: Sleep disorders are a complicated and major public
      health concern affecting millions of individuals. Obstructive sleep apnoea (OSA)
      is a common but still under-recognized disease which can cause intermittent
      nocturnal hypercapnia. Neuropeptides play critical roles in neurotransmission,
      acting as transmitters or modulators. Results from recent studies have implicated
      several neuropeptides in sleep and breathing regulation, including orexin,
      neuropeptides Y and galanin. Therefore, the present study aimed to evaluate the
      influence of hypercapnia on these neuropeptides and their receptors in order to
      assess their potential role in the pathogenesis of OSA. METHODS: Fifteen C57BL/6J
      mice were randomly divided into three groups and exposed to moderate hypercapnia
      (5% CO(2) with balanced room air), or severe hypercapnia (10% CO(2) with balanced
      room air) or room air for 3 h (9:00-12:00 h), respectively. Immediately following
      exposure the brainstem and hypothalamus were excised for real-time reverse
      transcription polymerase chain reaction and western blot analyses. RESULTS: In
      the hypothalamus gene expression including galanin, orexin and neuropeptide Y
      receptor 1 (NPYR1) was downregulated by hypercapnia. However, protein and mRNA
      levels of orexin-A receptor were upregulated by severe hypercapnia. In the
      brainstem only NPYR1 mRNA expression was decreased in moderate hypercapnia
      compared with that in severe hypercapnia. CONCLUSIONS: These findings suggest
      that hypercapnia can affect these neuropeptides and their receptors, especially
      the orexin and orexin-A receptor. The potential relationships between these
      peptides and OSA are worthy of further investigation.

PMID- 22882588
TI  - Hyperdynamic mesenteric circulation in cirrhosis: humoral or neural mechanism?

PMID- 22882589
TI  - Peripheral stem cell harvest using regular chemotherapy schedules in childhood
      cancer.
AB  - Prediction of the best moment for the harvest of PBSCs after standard
      chemotherapy followed by filgrastim in children with cancer is difficult. We
      retrospectively analyzed the moment of harvesting of 152 procedures in 94
      patients. The start of apheresis was guided by WBC count and CD34+ cell
      measurement in peripheral blood. We defined the first day of filgrastim
      administration, after completion of mobilizing chemotherapy, as day 1. Median
      time to harvest in different subgroups is as follows: neuroblastoma 11 days
      (range, 6-29 days), Ewing's sarcoma nine days (range, 7-15 days), brain tumor 10
      days (range, 7-15 days), relapsed Wilms' tumor 16 days (range, 9-20 days), and
      extracranial GCT seven days (range, 6-14 days). Patients harvested after
      cyclophosphamide priming (time to harvest within a range of 8-9 days) were
      analyzed as a separate group. The optimal moment for harvesting in different
      types of tumors was highly variable, although most consistent in patients
      diagnosed with Ewing's sarcoma or brain tumors and after cyclophosphamide
      priming.

PMID- 22882590
TI  - Editorial: diamond jubilees.

PMID- 22882591
TI  - Editorial comment: Laparoscopic bilateral native nephrectomies with simultaneous
      kidney transplantation.

PMID- 22882592
TI  - Histologic and immunohistochemical review of splenic fibrohistiocytic nodules in
      dogs.
AB  - BACKGROUND: Splenic fibrohistiocytic nodules (SFHN) are commonly diagnosed. It is
      suspected that these represent a heterogeneous group of malignant and
      nonmalignant diseases, separation of which could improve the ability of
      clinicians to prognosticate for dogs. HYPOTHESIS/OBJECTIVES: Immunohistochemistry
      will differentiate histologic diagnoses within the group of SFHN; survival after
      splenectomy is associated with those histologic types. ANIMALS: Thirty-two dogs
      with SFHN treated by or under direction from veterinary oncologists. METHODS:
      Retrospective case record analysis from dogs followed from splenectomy until
      death. Clinical, histopathologic, and immunohistochemistry data analyzed for an
      association with survival time. RESULTS: Thirty-two dogs had SFHN; grade 1 (2
      dogs), grade 2 (9 dogs), and grade 3 (lymphoid percentage <40%; 21 dogs). Twenty
      two dogs died, 10 were censored (9 alive median of 883 days after splenectomy).
      Median overall survival was 387 days, and grade 3 SFHN was negatively [corrected]
      associated with survival time as previously reported (P < .001). Of 31 available
      samples, dogs had diseases reclassified as nodular hyperplasia (13; 8 complex, 5
      lymphoid including 2 marginal zone), lymphoma (4; 2 marginal zone lymphoma, 1
      high grade B-cell lymphoma, and 1 marginal zone transitional to high grade B-cell
      lymphoma), 8 stromal sarcomas, and 6 histiocytic sarcomas. Dogs with histiocytic
      sarcoma had worse survival (median 74 days) than dogs with other diseases.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Splenic histiocytic sarcoma is an aggressive
      disease; however, some dogs with stromal sarcomas had long survival times. The
      term SFHN is no longer warranted for this group of disorders.

PMID- 22882593
TI  - A rare initial presentation of esophageal involvement in pemphigus.

PMID- 22882594
TI  - Fluorescence in situ hybridization for the differential diagnosis between Spitz
      naevus and spitzoid melanoma.
AB  - AIMS: The differential diagnosis between Spitz naevus and spitzoid melanoma can
      be extremely difficult, or even impossible. In recent years, many attempts have
      been made to find specific histopathological or immunohistochemical markers,
      although none has proved successful. Because the prognosis and treatment of each
      are very different, it is important to distinguish between these entities. We
      evaluated the ability of the fluorescence in situ hybridization (FISH) assay
      designed to detect the copy number of the RREB1 (6p25), MYB (6q23) and CCND1
      (11q13) genes and of centromere 6 (Cep 6)-in order to distinguish between Spitz
      naevus and spitzoid melanoma. METHODS AND RESULTS: We evaluated 12 spitzoid
      melanomas and six Spitz naevi from our records. The diagnosis of both conditions
      was based on previously described histopathological criteria. We obtained
      valuable results for FISH in eight spitzoid melanomas and five Spitz naevi.
      Chromosomal aberrations were detected in seven of the eight spitzoid melanomas
      (FISH-positive) and in none of the five Spitz naevi. The FISH-negative spitzoid
      melanoma was the least typical in its group. CONCLUSIONS: FISH was able to
      distinguish between Spitz naevus and spitzoid melanoma, with a sensitivity of
      87.5% and a specificity of 100%. Our findings suggest that FISH could prove a
      useful tool in the differential diagnosis between these entities.

PMID- 22882596
TI  - Ovarian steroid regulation of endometrial phospholipase A2 isoforms in horses.
AB  - Real-time PCR was used to investigate the role of progesterone (P4) and
      oestradiol (E2) in regulation of endometrial cytosolic, secretory and calcium
      independent phospholipase A2 (PLA2G4A, PLA2G2A and PLA2G6, respectively) gene
      expression. Ovariectomized mares underwent 6 days of E2 pre-treatment followed by
      14 days of P4 supplementation. At the start of P4 treatment (Day 1), mares were
      assigned in a 2 * 2 factorial design to receive either E2 or vehicle starting on
      Day 11 and endometrial biopsy collection on either Day 14 when P4 concentrations
      remained high (>4 ng/ml) or Day 16 when P4 concentrations had declined (0.5-2
      ng/ml). Additional biopsies were collected from ovariectomized mares on Day 8,
      which served as control. Blood samples were collected for P4 determination.
      PLA2G4A expression was higher (p < 0.05) on Day 14 compared with Day 8. In
      contrast, PLA2G2A did not change significantly (p < 0.12). PLA2G4A and PLA2G2A
      gene expression increased (p < 0.05), as P4 concentration dropped, on Day 16. In
      contrast, PLA2G6 gene expression did not show differences between days. Treatment
      with oestradiol did not increase PLA2 isoforms expression when compared to
      treatment with the vehicle. PLA2G4A and PLA2G2A were positively correlated with
      each other and negatively correlated with P4 concentrations. In conclusion, P4
      withdrawal upregulated PLA2G4A and PLA2G2A gene expression, and this was not
      affected by E2. PLA2G4A and PLA2G2A but not PLA2G6 gene expression may be
      involved in controlling prostaglandin F2 alpha synthesis and luteolysis.

PMID- 22882595
TI  - Environmental factors associated with American cutaneous leishmaniasis in a new
      Andean focus in Colombia.
AB  - OBJECTIVE: To evaluate the environmental and ecological factors associated with
      Leishmania transmission and vector abundance in Chaparral, Tolima-Colombia.
      METHODS: First, we compared the ecological characteristics, abundance of
      phlebotomies and potential reservoir hosts in the peridomestic environment (100 m
      radius) of randomly selected houses, between two townships with high and low
      cutaneous leishmaniasis incidence. Second, we examined peridomestic correlates of
      phlebotomine abundance in all 43 houses in the higher risk township. RESULTS: The
      high transmission township had higher coverage of forest (23%vs. 8.4%) and shade
      coffee (30.7%vs. 11%), and less coffee monoculture (16.8%vs. 26.2%) and pasture
      (6.3%vs. 12.3%), compared to the low transmission township. Lutzomyia were more
      abundant in the high transmission township 2.5 vs. 0.2/trap/night. Lutzomyia
      longiflocosa was the most common species in both townships: 1021/1450 (70%) and
      39/80 (49%). Numbers of potential wild mammal reservoirs were small, although
      four species were found to be infected with Leishmania (Viannia) spp. In the high
      transmission township, the overall peridomiciliary capture rate of L.
      longiflocosa was 1.5/trap/night, and the abundance was higher in houses located
      nearer to forest (rho = -0.30, P = 0.05). CONCLUSION: The findings are consistent
      with a domestic transmission cycle with the phlebotomies dependent on dense
      vegetation near the house.

PMID- 22882597
TI  - "Assessment of chronic sclerodermoid Graft-versus-Host Disease patients, using 20
      MHz high-frequency ultrasonography and cutometer methods".
AB  - The development of an adverse graft-versus-host disease (GvHD) is a major
      complication of stem cell transplantations, which are widely used to cure
      increasing number of hematologic malignancies. Patients with chronic GvHD are at
      risk of joint contractures secondary to sclerodermatous skin changes. Several
      clinical scores or serologic markers have been used to assess skin sclerosis in
      scleroderma patients. Evaluation of sclerotic skin changes using biometric tools
      remains to be challenging. The purpose of this study was to illustrate and
      exemplify ultrasound measurement and measurement of skin elasticity of five
      chronic sclerodermoid GvHD patients. There is still a substantial lack of studies
      using objective and non-invasive methods helpful in assessment of patients with
      skin involvement of GvHD. Although ultrasound is not the ideal method, it is
      worth emphasizing that it is still useful, non-invasive, and repeatable device in
      monitoring patients suffering from GvHD. It should also be added, that it seems
      to be advisable to repeat USG examination at an interval of 3 months after the
      treatment. In addition, skin echogenicity may be a more sensitive parameter than
      skin thickness in assessment of cGvHD patients.

PMID- 22882598
TI  - Design of multifunctional gold nanoparticles for in vitro and in vivo gene
      silencing.
AB  - Over the past decade, the capability of double-stranded RNAs to interfere with
      gene expression has driven new therapeutic approaches. Since small interfering
      RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA
      interference (RNAi), efforts were directed toward the development of efficient
      delivery systems to preserve siRNA bioactivity throughout the delivery route,
      from the administration site to the target cell. Here we provide evidence of RNAi
      triggering, specifically silencing c-myc protooncogene, via the synthesis of a
      library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of
      the AuNPs is demonstrated using a hierarchical approach including three
      biological systems of increasing complexity: in vitro cultured human cells, in
      vivo invertebrate (freshwater polyp,  Hydra ), and in vivo vertebrate (mouse)
      models. Our synthetic methodology involved fine-tuning of multiple structural and
      functional moieties. Selection of the most active functionalities was assisted
      step-by-step through functional testing that adopted this hierarchical strategy.
      Merging these chemical and biological approaches led to a safe, nonpathogenic,
      self-tracking, and universally valid nanocarrier that could be exploited for
      therapeutic RNAi.

PMID- 22882599
TI  - Skin prick test reactivity to aeroallergens by filaggrin mutation status.
AB  - BACKGROUND: Studies have shown that filaggrin gene (FLG) mutations are positively
      associated with sensitization to aero allergens. We hypothesized that FLG
      mutations would also have an effect on the mean size of positive skin prick test
      (SPT) reactions as well as the number of positive reactions. OBJECTIVE: To
      investigate the effect of FLG mutations on the mean size and the number of
      positive SPT reactions, as well as the association with positive specific IgE.
      METHODS: A random sample of 3335 adults from the general population in Denmark
      was genotyped for the R501X and 2282del4 mutations in the FLG. SPT and specific
      IgE measurements to common aeroallergens were also performed. RESULTS: FLG
      mutations did not influence the mean size and number of positive SPT reactions.
      Also, no association was found between FLG mutations and specific IgE
      measurements. CONCLUSION: Our findings suggest that FLG mutations alone are
      insufficient to cause secondary sensitization to allergens. The positive
      association seen in patients must be explained by a combination of further
      barrier abnormality caused by dermatitis as well as increased allergen exposure.

PMID- 22882600
TI  - Is pursuit of termination of atrial fibrillation during catheter ablation of
      great value in patients with longstanding persistent atrial fibrillation?
AB  - BACKGROUND: The reliable endpoint for ablation of longstanding persistent atrial
      fibrillation (LPAF) has not been clearly established. METHODS AND RESULTS: This
      study included 140 patients who underwent catheter ablation for drug-refractory
      LPAF. A stepwise ablation approach included circumferential pulmonary vein
      isolation followed by left atrial and right atrial complex fractionated
      electrogram-guided ablation. Atrial fibrillation (AF) was terminated by
      radiofrequency application during catheter ablation in 95 patients (67.9%). Among
      them, 33 patients (23.6%) converted to sinus rhythm directly, whereas 62 patients
      (44.3%) via atrial tachycardias (ATs). Patients in whom AF terminated during the
      index procedure had a lower recurrence rate of atrial arrhythmia than patients in
      whom AF did not terminate (45.3% vs 68.9%, P = 0.009, follow-up 18.7 +/- 7.6
      months). Among patients in whom AF terminated, there was no significant
      difference in recurrence rate according to the termination mode, whether
      converted to AT or not (P = NS). However, patients who converted to AT had a
      higher recurrence rate of AT (54.8% vs 81%; P = 0.016). Multivariable logistic
      regression analysis demonstrated that termination of AF during ablation (HR
      0.440; 95% CI: 0.200-0.969, P = 0.041) and structural heart disease (HR 2.633;
      95% CI: 1.211-5.723; P = 0.015) were significant independent factors predicting
      the recurrence of atrial arrhythmia. CONCLUSIONS: Termination of AF during
      catheter ablation is associated with a better clinical outcome in patients with
      LPAF.

PMID- 22882601
TI  - Bacteriology laboratories and musculoskeletal tissue banks in Australia.
AB  - In Australia, there are six Therapeutic Goods Administration-licensed clinical
      bacteriology laboratories providing bacterial and fungal bioburden testing of
      allograft musculoskeletal samples sent from 10 tissue banks. Musculoskeletal swab
      and/or tissue biopsy samples are collected at the time of allograft retrieval and
      sent to bacteriology laboratories for bioburden testing, in some cases requiring
      interstate transport. Bacteria and fungi may be present within the allograft at
      the time of retrieval or contaminated from an external source. The type of
      organism recovered will determine if the allograft is rejected for transplant,
      which may include all allografts from the same donor. Bacteriology staff also
      provides unpaid support of tissue banks through meeting involvement,
      consultations, licence-related activities, validations and research funded by
      their organisation and not part of any contractual agreement. Bacteriology
      laboratories and tissue banks must be compliant to the Code of Good Manufacturing
      Practice - Human Blood and Tissues and regulated by the Therapeutic Goods
      Administration. Clinical bacteriology laboratories also require mandatory
      accreditation to Standards Australia International Organisation for
      Standardisation (ISO) 15189:2009 medical laboratories - particular requirements
      for quality and competence, and may also attain Standards Australia/New Zealand
      Standard ISO 9001:2000 quality management systems certification. Bacteriology
      laboratories and musculoskeletal tissue banks are integral partners in providing
      safe allograft musculoskeletal tissue for transplant.

PMID- 22882602
TI  - Alveolar ridge augmentation using implants coated with recombinant human
      growth/differentiation factor -5 (rhGDF-5). Radiographic observations.
AB  - OBJECTIVES: Application of growth factors onto dental implant surfaces is being
      considered to support local bone formation. Bone morphogenetic protein-2 (BMP-2)
      and BMP-7 have been shown to support local bone formation, but are also
      associated with adverse events including seroma formation, extensive bone
      remodeling, and implant displacement captured in the radiographic evaluation.
      This report presents mineralized tissue formation and associated adverse events
      following implantation of recombinant human growth/differentiation factor-5
      (rhGDF-5) coated onto a purpose-designed titanium porous-oxide implant surface.
      MATERIAL AND METHODS: Twelve young adult Labrador dogs were used. Three 10-mm
      titanium implants/jaw quadrant were placed 5 mm into the alveolar ridge in the
      posterior mandible following surgical extraction of the premolar teeth and
      reduction of the alveolar ridge. Six animals received implants coated with rhGDF
      5 at 30 or 60 MUg/implant in contralateral jaw quadrants. Six animals received
      implants coated with rhGDF-5 at 120 MUg/implant or uncoated implants (sham
      surgery control) using the same split-mouth design. The mucoperiosteal flaps were
      advanced, adapted, and sutured to submerge the implants. Radiographic recordings
      were made immediately postsurgery (baseline), and at week 4 and 8 (end of study).
      Two masked examiners performed the analysis using computer enhanced radiographic
      images. RESULTS: rhGDF-5 coated implants displayed mineralized tissue formation
      significantly exceeding that of the sham-surgery control in a dose-dependent
      order. The greatest increase was observed for implants coated with rhGDF-5 at 60
      MUg and 120 MUg amounting to approximately 2.2 mm for both groups at 8 weeks.
      Importantly, none of the implants showed evidence of peri-implant bone
      remodeling, implant displacement, or seroma formation. The newly formed
      mineralized tissues assumed characteristics of the resident bone. CONCLUSIONS:
      rhGDF-5 coated onto a titanium porous-oxide implant surface exhibits a dose
      dependent potential to stimulate local mineralized tissue formation. Application
      of rhGDF-5 appears safe as it is associated with limited, if any, adverse events.

PMID- 22882603
TI  - The prevalence of dentine hypersensitivity in the general population in China.
AB  - Dentine hypersensitivity (DH) is a common condition that is frequently
      encountered in dental practice. The aim of this multi-centre and cross-sectional
      study was to establish the prevalence of DH in the general population in China. A
      total of 6843 subjects were questioned and examined using a triple syringe with a
      blast of cold air to confirm the diagnosis of DH. The sensitive surface, loss of
      attachment and gingival recession of sensitive teeth were measured and recorded.
      Of the 2932 subjects reporting hypersensitive symptoms, 2363 subjects were
      further diagnosed as DH, giving an overall prevalence of 34.5%. The greatest
      number of subjects with DH were within the 50-59 years age group (P < 0.01). The
      most commonly affected teeth were the premolars and the most provoking factor was
      the presence of a cold stimulus. The prevalence of DH in a representative sample
      of the general population in China was 34.5%, indicating that DH is a common oral
      problem. Therefore, the recognition of the condition and subsequent treatment by
      the dentist is therefore essential if the condition is to be managed correctly.

PMID- 22882604
TI  - Anaesthetic complications in pigs undergoing MRI guided convection enhanced drug
      delivery to the brain: a case series.
AB  - OBSERVATIONS: A total of 13 intracerebral infusions were performed at
      approximately 1 month intervals in three NIH miniature pigs over the age range of
      31-59 weeks. Pigs received azaperone and ketamine premedication to allow venous
      cannulation and propofol induction of anaesthesia. Anaesthesia was maintained
      with isoflurane throughout cranial surgery and MRI scanning. Physiological
      monitoring during surgery consisted of blood pressure, pulse, temperature and
      oxygen saturation monitoring, ECG and capnography. Analgesia consisted of
      meloxicam and morphine. However, during MRI scanning blood pressure and ECG
      monitoring had to be discontinued. Anaesthetized pigs underwent intermittent
      intraputamenal convection enhanced delivery (CED) of gadolinium with real-time
      magnetic resonance imaging. Progressive tachycardia was consistently observed in
      all pigs during CED with a mean +/- SD maximum increase of 41 +/- 22 beats
      minute(-1) from a baseline heart rate of 96 +/- 9 minute(-1) . The heart rate
      remained elevated until recovery. A mean reduction in body temperature of 2.8 +/-
      0.6  degrees C from the start of anaesthesia was also observed during the period
      of MRI scanning. All pigs recovered from anaesthesia smoothly and heart rates
      returned to normal during the recovery period. CONCLUSIONS: Hypothermia is common
      in pigs undergoing this sedation and anaesthesia protocol. Convection enhanced
      delivery of drugs in healthy anaesthetized pigs may result in tachycardia.

PMID- 22882605
TI  - Breast-related CSF shunt complications: literature review with illustrative case.
AB  - In this article, we discuss and classify breast-related ventriculoperitoneal (VP)
      cerebrospinal fluid (CSF) shunt complications, and provide a literature review.
      Shunt complications related to pre-existing breast implants comprise nearly half
      of the breast-related shunt complications reported thus far. We present a
      complication of shunt failure in a 61-year-old woman who had previously undergone
      mastectomies for breast cancer with implant reconstruction. Following shunting,
      she developed headaches, fever, and right-sided breast swelling and erythma
      consequent to breast implant rupture, distal shunt migration, and CSF pseudocyst.
      This case is unique in that it involved rupture of a breast implant from VP shunt
      insertion. For complication avoidance, neurosurgeons should be aware of the
      potential pitfalls in shunting patients with breast implants.

PMID- 22882606
TI  - International reference reagents to standardise blood group genotyping:
      evaluation of candidate preparations in an international collaborative study.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to evaluate, in an
      international collaboration, four lyophilised genomic DNA preparations, selected
      from genotyped and phenotyped donors by the study organisers, for their
      suitability to standardise and control blood group genotyping procedures for
      common ancestral Caucasian and Black African alleles. MATERIALS AND METHODS:
      Twenty-nine laboratories performed 'blind' testing of replicated ampoules of the
      candidate reference reagents, RBC1 (10/232), RBC4 (10/236), RBC5 (10/238) and
      RBC12 (10/234), using a range of genotyping procedures, most commonly classical
      PCR using allele or sequence specific primers. RESULTS: The majority of
      laboratories reported blood group genotypes in accordance with those determined
      by the study organisers and the serological phenotypes. Despite an overall high
      level of accuracy in genotyping, the identified errors and inconsistencies, and
      the limited genotyping capabilities of many laboratories, confirmed the need for
      validated reference materials to control test procedures. CONCLUSIONS: The
      establishment of RBC1, RBC4, RBC5 and RBC12 as World Health Organization
      Reference Reagents will facilitate international standardisation of blood group
      genotyping and ensure that such tests are sufficiently sensitive and specific.

PMID- 22882607
TI  - A descriptive study of the equine proximal interphalangeal joint using magnetic
      resonance imaging, contrast arthrography, and arthroscopy.
AB  - OBJECTIVE: To describe regions of the thoracic and pelvic limb proximal
      interphalangeal (PIP) joints that are arthroscopically accessible and identify
      soft tissue structures that should be avoided during arthroscope and instrument
      placement. STUDY DESIGN: Experimental ex vivo descriptive study. ANIMALS: Horses
      (n = 15). METHODS: Cadaver limbs (n = 36) were used for anatomic modeling,
      magnetic resonance imaging (MRI) with MRI-compatible needles, computed tomography
      with contrast arthrography, and arthroscopy of the PIP joint. Two arthroscopic
      approaches to the dorsal joint pouch were compared. RESULTS: With arthroscopy,
      62.4% of the joint perimeter could be observed from the dorsal and palmar/plantar
      joint pouches with no significant difference in the amount of joint observed when
      using the more proximal or distal approach to the dorsal joint pouch (P =.59).
      CONCLUSION: The dorsal and palmar/plantar joint pouches provide adequate
      arthroscopic visibility for the axial portions of the articular surface of the
      proximal and middle phalanx. The abaxial portions of the articular surface were
      difficult to view because of narrowing of the joint pouches abaxially. When
      comparing the proximal and distal approach to the dorsal joint pouch, arthroscope
      insertion 1.5 cm proximal to the joint allowed the easiest manipulation of the
      arthroscope. Palmar/plantar portals were placed dorsal to the neurovascular
      bundle, proximal to the epicondyle of the middle phalanx to prevent tendon and
      ligament injury.

PMID- 22882608
TI  - Shoulder arthrodesis in 14 dogs.
AB  - OBJECTIVES: To report surgical technique and clinical outcome of shoulder
      arthrodesis in dogs. STUDY DESIGN: Multicenter clinical case series. ANIMALS:
      Dogs (n = 14). METHODS: Shoulder arthrodesis featured craniolateral plate and
      screw application, with application of a 2nd plate and screws craniolaterally or
      caudolaterally in 5 shoulders. Implants included the locking string of pearls
      (SOP)TM plate in 7 shoulders. Subjective preoperative, 5-8 weeks postoperative,
      and 11-16 weeks postoperative clinical and radiographic findings were documented.
      Owner questionnaire evaluation of outcome was performed 6-20 months
      postoperatively. RESULTS: Mean angle of arthrodesis was 114 degrees  (range 102
      degrees -122 degrees ). Progression of arthrodesis was noted in 13/14 cases at
      both the 5-8 and 11-16 weeks postoperative radiographic assessments. Nine
      complications occurred in 7/14 dogs, graded as catastrophic in 2/9, major in 2/9,
      and minor in 5/9. Where morbidity was successfully managed, 11-16-week and 6-10
      month postoperative limb function was positive on both veterinary and owner
      evaluations in almost all cases, and in several, functional lameness was
      considered sufficiently mild as to be imperceptible on subjective veterinary
      evaluation. Where present, limb circumduction was noted as the major feature of
      persistent lameness. CONCLUSIONS: Shoulder arthrodesis in dogs results in
      acceptable limb function and should be considered for the management of
      debilitating shoulder pathology despite a high incidence of complications.
      Application of the SOP plate to aid shoulder arthrodesis warrants further study.

PMID- 22882609
TI  - Change in FS-T index in adults in the German national oral health surveys between
      1989 and 2005.
AB  - OBJECTIVES: To assess changes in the number of functioning teeth (filled and
      sound teeth, FS-T index) from 1989/1992 to 2005 in West and East Germany and to
      evaluate survey- and region-specific associations between sociodemographic and
      behavioral risk factors and the FS-T index. METHODS: Within the German Oral
      Health Studies, random samples from 35-44-year-olds were drawn in 1989, 1992,
      1997 and 2005. The FS-T index and a questionnaire with socioeconomic and
      behavioral items were assessed. Negative binomial regression models were
      evaluated, including all sociodemographic and behavioral factors simultaneously
      as independent variables. RESULTS: For West Germany, median FS-T index increased
      by 3 teeth between 1989 and 2005 (Ptrend < 0.001). In East Germans, FS-T index
      was similar in 1992 and 1997 (median, 24), but increased by one tooth until 2005
      (Ptrend < 0.001). For West and East Germany, middle and high school education
      were significantly associated with higher FS-T indices in all surveys, although
      effects were most pronounced in 2005. Being married, reporting regular dental
      visits and good oral hygiene were significantly related to a higher number of
      functioning teeth in at least one survey year. CONCLUSIONS: Dental health
      assessed as the number of functioning teeth improved between 1989/92 and 2005 in
      both German parts and across all educational levels. However, considering the
      educational level, dental health was less equally distributed in 2005 compared
      with previous surveys.

PMID- 22882610
TI  - Carbohydrate control over carotenoid build-up is conditional on fruit ontogeny in
      clementine fruits.
AB  - The final contents of primary and secondary metabolites of the ripe fruit depend
      on metabolic processes that are tightly regulated during fruit ontogeny.
      Carbohydrate supply during fruit development is known to influence these
      processes but, with respect to secondary metabolites, we do not really know
      whether this influence is direct or indirect. Here, we hypothesized that the
      sensitivity of clementine fruit metabolism to carbohydrate supply was conditional
      on fruit developmental stage. We applied treatments increasing fruit load
      reversibly or irreversibly at three key stages of clementine (Citrus clementina
      Hort. ex Tan.) fruit development: early after cell division, at the onset of
      fruit coloration (color break) and near maturity. The highest fruit load obtained
      by early defoliation (irreversible) had the highest impact on fruit growth,
      maturity and metabolism, followed by the highest fruit load obtained by early
      shading (reversible). Final fruit size decreased by 21 and 18% in these early
      irreversible and reversible treatments, respectively. Soluble sugars decreased by
      18% in the early irreversible treatment, whereas organic acids increased by 46
      and 29% in these early irreversible and reversible treatments, respectively.
      Interestingly, total carotenoids increased by 50 and 18%, respectively. Changes
      in leaf starch content and photosynthesis supported that these early treatments
      triggered a carbon starvation in the young fruits, with irreversible effects.
      Furthermore, our observations on the early treatments challenge the common view
      that carbohydrate supply influences positively carotenoid accumulation in fruits.
      We propose that early carbon starvation irreversibly promotes carotenoid
      accumulation.

PMID- 22882611
TI  - Advances in computational analysis of metagenome sequences.
AB  - Second-generation sequencing technologies are revolutionizing the study of
      metagenomes. Whole-genome shotgun sequencing of metagenomic DNA may become an
      attractive alternative to the current widely used ribosomal RNA gene studies.
      Large data sets of short sequence reads are mapped onto a custom microbial
      reference sequence. If a bacterial pangenome of completely sequenced genomes is
      taken as a reference, the output consists of the distribution of bacterial taxa
      in and bacterial gene contents of the metagenome. The relative abundance of
      functional categories and of individual pathways and fitness traits encoded by
      the metagenomic gene pool provides insight into habitat-specific features of the
      microbial community. Polymorphic sites in sequence reads may resolve the number
      and abundance of individual clonal complexes of dominant species in the
      polymicrobial community. These SNPs and de novo mutations may be exploited to
      trace the spatiotemporal spread of clones and the emergence of novel traits such
      as fitness or resistance determinants. In conclusion, massively parallel
      sequencing of metagenomic DNA allows deep insights into the composition and the
      genetic repertoire of polymicrobial communities.

PMID- 22882612
TI  - Rapid transmission of Gyrodactylus salaris (Malmberg, 1957) between live Arctic
      charr, Salvelinus alpinus (L.), fry.

PMID- 22882614
TI  - Incidence and predictors of left atrial thrombus in patients with rheumatic
      mitral stenosis and sinus rhythm: a transesophageal echocardiographic study.

PMID- 22882615
TI  - Proper use of left atrial ejection force as a measure of left atrial mechanical
      function.

PMID- 22882618
TI  - Deletion of the complement phagocytic receptors CR3 and CR4 does not alter
      susceptibility to experimental cerebral malaria.
AB  - Complement receptors for C3-derived fragments (CR1-4) play critical roles in
      innate and adaptive immune responses. Of these receptors, CR3 and CR4 are
      important in binding and phagocytosis of complement-opsonized pathogens including
      parasites. The role of CR3 and CR4 in malaria or in cerebral malaria (CM) has
      received little attention and remains poorly understood in both human disease and
      rodent models of malaria. CR3 and CR4 are members of the beta(2) -integrin family
      of adhesion molecules and are expressed on all leucocytes that participate in the
      development of CM, most importantly as it relates to parasite phagocytosis
      (monocytes/macrophages) and antigen processing and presentation (dendritic
      cells). Thus, it is possible that these receptors might play an important role in
      disease development. To address this question, we examined the role of CR3(-/-) 
      and CR4(-/-)  in experimental cerebral malaria (ECM). We found that both CR3(-/-)
      and CR4(-/-)  mice were fully susceptible to ECM and developed disease
      comparable to wild-type mice. Our results indicate that CR3 and CR4 are not
      critical to the pathogenesis of ECM despite their role in elimination of
      complement-opsonized pathogens. These findings support recent studies indicating
      the importance of the terminal complement pathway and the membrane attack complex
      in ECM pathogenesis.

PMID- 22882619
TI  - Early dynamic F18-FDG-PET shows a hypervascular pattern with central scar in a
      liver mass.

PMID- 22882620
TI  - Comparison of nurse burnout across Army hospital practice environments.
AB  - PURPOSE: The primary purpose of this study was to examine the nursing practice
      environment and burnout of nursing personnel assigned to a deployed combat
      support hospital (CSH). A secondary aim was to compare differences in the level
      of burnout between the deployed Army nursing personnel and Army nursing personnel
      assigned to an Army hospital in the United States that served as the U.S.
      military's primary referral center for American combat casualties evacuated from
      Iraq. DESIGN: A nonexperimental cross-sectional design was used for this study.
      METHODS: The Maslach Burnout Inventory and the Practice Environment Scale were
      administered to 105 personnel who deployed with a CSH to Iraq. Data from this
      study were linked to data obtained from 152 nursing personnel who participated in
      an earlier burnout study at a large Army hospital in the United States. The
      linked datasets yielded a final sample of 257 Army nursing personnel. Analysis of
      variance and linear regression analysis were used to analyze these data.
      FINDINGS: Emotional exhaustion was common across groups. For the deployed nursing
      personnel, emotional exhaustion was related to a perceived lack of support from
      management, foundations for quality of care, collegial relationships, and
      extended work schedules. The U.S.-based Army hospital group scored significantly
      higher emotional exhaustion, but it was related to the additional
      responsibilities associated with being an Army nurse, working extended schedules,
      and working with combat casualties for extended periods of time. The U.S.-based
      group perceived more personal accomplishment from the work they do. CONCLUSIONS:
      Burnout was common across Army hospital settings. Emotional exhaustion was most
      problematic in the U.S.-based Army hospital; however, there was less cynicism
      toward patients and a greater perception of personal accomplishment associated
      with work. CLINICAL RELEVANCE: This study supports the importance of a
      professional practice environment for Army nursing personnel both during
      deployment and in U.S.-based Army hospitals.

PMID- 22882621
TI  - Editorial comment: Size and location of defects at the coupling interface affect
      lithotripter performance.

PMID- 22882622
TI  - The Assessment of Recovery Capital: properties and psychometrics of a measure of
      addiction recovery strengths.
AB  - INTRODUCTION AND AIMS: Sociological work on social capital and its impact on
      health behaviours have been translated into the addiction field in the form of
      'recovery capital' as the construct for assessing individual progress on a
      recovery journey. Yet there has been little attempt to quantify recovery capital.
      The aim of the project was to create a scale that assessed addiction recovery
      capital. DESIGN AND METHODS: Initial focus group work identified and tested
      candidate items and domains followed by data collection from multiple sources to
      enable psychometric assessment of a scale measuring recovery capital. RESULTS:
      The scale shows moderate test-retest reliability at 1 week and acceptable
      concurrent validity. Principal component analysis determined single factor
      structure. DISCUSSION AND CONCLUSIONS: The Assessment of Recovery Capital (ARC)
      is a brief and easy to administer measurement of recovery capital that has
      acceptable psychometric properties and may be a useful complement to deficit
      based assessment and outcome monitoring instruments for substance dependent
      individuals in and out of treatment.

PMID- 22882623
TI  - In vitro prediction of in vivo skin damage associated with the wiping of dry
      tissue against skin.
AB  - BACKGROUND: The ideal gentle cleansing product is one that effectively removes
      soils while minimizing damage to the skin. Thus, measuring physical abrasion
      caused by cleansing tissues is critical to the continued development of gentle
      cleansing products. Current analysis of cleansing materials for skin gentleness
      is time consuming and requires expensive human subject testing. This report
      describes the development of a rapid and inexpensive bench assay for the
      assessment of skin abrasion caused by wiping. METHODS: Coefficient of friction
      (COF) evaluations using bench methods were compared with results from clinical
      studies of repeated wiping and with confocal visualizations of excised skin. A
      Monitor/Slip and Friction instrument (model 32-06; TMI, Amityville, NY, USA) was
      used to measure tissue friction on simulated skin (Vitro-Skin, N19-5X; IMS,
      Milford, CT, USA). Clinical data from a 4-day repetitive forearm wiping study
      measuring transepidermal water loss (TEWL) in 30 subjects was compared with
      results from the bench top assay. In addition, excised skin samples were also
      treated using the COF bench assay and examined using confocal microscopy to
      visualize stratum corneum damage caused by wiping. RESULTS: Using the bench COF
      assay, we were able to distinguish between bath tissue codes by comparing average
      static friction value (ASFV) for the test codes, where lower ASFV indicated less
      abrasive tissue. The ASFV followed the same gentleness trend observed in the
      clinical study. Confocal microscopy of excised skin wiped with the same materials
      indicated stratum corneum damage consistent with the bench COF and clinical TEWL
      observations. CONCLUSION: We observed significant correlation between bench and
      clinical methods for measuring skin damage caused by wiping of skin with tissue.
      The bench method will facilitate rapid and inexpensive skin gentleness assessment
      of cleansing materials.

PMID- 22882624
TI  - Anesthesia for surgery related to craniosynostosis: a review. Part 2.
AB  - The management of children with craniosynostosis is multidisciplinary and has
      evolved significantly over the past five decades. The treatment is primarily
      surgical. The anesthetic challenges continue to be the management of massive
      blood transfusion and prolonged anesthesia in small children, often further
      complicated by syndrome-specific issues. This two-part review aims to provide an
      overview of the anesthetic considerations for these children. The first part
      described the syndromes associated with craniosynostosis, the provision of
      services in the UK, surgical techniques, preoperative issues and induction and
      maintenance of anesthesia. This second part will explore hemorrhage control, the
      use of blood products, metabolic disturbance and postoperative issues.

PMID- 22882625
TI  - Clinical impact of liquid-based cytology test on diagnostic yields from
      transbronchial needle aspiration.
AB  - BACKGROUND AND OBJECTIVE: Transbronchial needle aspiration (TBNA) is a well
      established diagnostic method that is underutilized due to the relatively high
      percentage of non-diagnostic samples and low success rates. This study was
      designed to evaluate the impact of liquid-based cytology test (LBC) on the
      diagnostic yield from TBNA. METHODS: Ninety-seven consecutive patients who
      underwent TBNA due to significant mediastinal adenopathy were enrolled in the
      study. Each target site was aspirated four times, with the first and third
      aspirates being prepared for LBC and the second and fourth aspirates being
      reserved for conventional pick-and-smear (CPS) cytology. RESULTS: Paired
      aspirates were obtained from 114 target sites, giving a total of 228 test samples
      from 97 consecutive patients. The overall diagnostic sensitivity of TBNA was
      63.6% (56/88). The yields from small cell lung cancers were better than those
      from non-small cell lung cancers (P < 0.05), and TBNA of subcarinal nodes
      provided better diagnostic yields (P < 0.05). Nodal diameters > 20 mm on computed
      tomography were also associated with better yields than nodes with diameters of
      10-20 mm (P = 0.001). The diagnostic sensitivity of TBNA was similar for each
      processing method-59.8% (61/102) for LBC and 64.7% (65/102) for CPS. CONCLUSIONS:
      LBC was not inferior to CPS with respect to diagnostic yields from TBNA, and
      enabled efficient pathological evaluation.

PMID- 22882626
TI  - Identification of microRNA-regulated autophagic pathways in plant lectin-induced
      cancer cell death.
AB  - OBJECTIVES: Plant lectins, carbohydrate-binding proteins of non-immune origin,
      have recently been reported to induce programmed cell death (including apoptosis
      and autophagy) in many types of cancer cells. MicroRNAs (miRNAs), small, non
      coding endogenous RNAs, ~22 nucleotides (nt) in length, have been well
      characterized to play essential roles in regulation of the autophagy process in
      cancer; however, how these miRNAs regulate autophagic pathways in plant lectin
      induced cancer cells, still remains an enigma. MATERIALS AND METHODS:
      Identification of microRNA-regulated autophagic pathways was carried out using a
      series of elegant systems - biology and bioinformatics approaches, such as
      network construction, hub protein identification, targeted microRNA prediction,
      microarray analyses and molecular docking. RESULTS: We computationally
      constructed the human autophagic protein-protein interaction (PPI) network, and
      further modified this network into a plant lectin-induced network. Subsequently,
      we identified 9 autophagic hub proteins and 13 relevant oncogenic and tumour
      suppressive miRNAs, that could regulate these aforementioned targeted autophagic
      hub proteins, in human breast carcinoma MCF-7 cells. In addition, we confirmed
      that plant lectins could block the sugar-containing receptor EGFR-mediated
      survival pathways, involved in autophagic hub proteins and relevant miRNAs,
      thereby ultimately culminating in autophagic cell death. CONCLUSIONS: These
      results demonstrate that network-based identification of microRNAs modulate
      autophagic pathways in plant lectin-treated cancer cells, which may shed new
      light on the discovery of plant lectins as potent autophagic inducers, for cancer
      drug discovery.

PMID- 22882627
TI  - Screening for dilated cardiomyopathy in Great Danes in the United Kingdom.
AB  - BACKGROUND: Great Danes (GD) are predisposed to dilated cardiomyopathy (DCM), but
      little is known about progression, clinical manifestations, or inheritance in
      dogs in the UK. For echocardiographic screening, breed-specific reference
      intervals (RI) are required. OBJECTIVES: To document the prevalence, clinical
      manifestations, and inheritance of DCM in UK GD. To establish RI for Doppler
      echocardiography (ECHO) in GD. ANIMALS: One hundred and seven client-owned GDs.
      METHODS: Echocardiographic screening study. Dogs were scored on ECHO and ECG
      variables and classified as normal (NORM), equivocal (EQUIV), or affected (AFX).
      Forty NORM dogs were used to determine RI for ECHO. Pedigrees from all dogs were
      examined for mode of inheritance. RESULTS: The prevalence of DCM in this
      population, based on score, was 35.6%. Significant differences in M mode left
      ventricular dimensions (MMLVD) were identified between male and female dogs (P <
      .011). RI for MMLVD and transformed MMLVD (allometric scaling) were lower than
      previously suggested. When dogs were reclassified using amended RI for MMLVD,
      prevalence increased to 47%. End-systolic volume index more reliably identified
      AFX dogs than other systolic function indices. Ventricular arrhythmias (VA) were
      commonly identified, with the highest prevalence in AFX dogs (54%). Pedigree
      analysis suggested an autosomal dominant mode of inheritance. CONCLUSIONS AND
      CLINICAL IMPORTANCE: The prevalence of DCM in UK GD is higher than previously
      reported and autosomal dominant inheritance is likely. Sex or body weight
      dependent RI should be used for ECHO in GD and current RI might underestimate
      ESVI in GD. VA might play an important role in GD with DCM.

PMID- 22882628
TI  - Sexual violence in post-conflict Liberia: survivors and their care.
AB  - Using routine data from three clinics offering care to survivors of sexual
      violence (SV) in Monrovia, Liberia, we describe the characteristics of SV
      survivors and the pattern of SV and discuss how the current approach could be
      better adapted to meet survivors' needs. There were 1500 survivors seeking SV
      care between January 2008 and December 2009. Most survivors were women (98%) and
      median age was 13 years (Interquartile range: 9-17 years). Sexual aggression
      occurred during day-to-day activities in 822 (55%) cases and in the survivor's
      home in 552 (37%) cases. The perpetrator was a known civilian in 1037 (69%) SV
      events. Only 619 (41%) survivors sought care within 72 h. The current approach
      could be improved by: effectively addressing the psychosocial needs of child
      survivors, reaching male survivors, targeting the perpetrators in awareness and
      advocacy campaigns and reducing delays in seeking care.

PMID- 22882629
TI  - Dermatofibrosarcoma protuberans of the breast.

PMID- 22882630
TI  - Expression of the glucose transporter HXT1 involves the Ser-Thr protein
      phosphatase Sit4 in Saccharomyces cerevisiae.
AB  - We studied the effect of the loss of the Ser-Thr protein phosphatase Sit4, an
      important post-translational regulator, on the steady-state levels of the low
      affinity glucose transporter Hxt1p and observed a delay in its appearance after
      high glucose induction, slow growth, and diminished glucose consumption. By
      analyzing the known essential pathway necessary to induce Hxt1p, we observed a
      partial inhibition of casein kinase I activity. In both WT and sit4Delta strains,
      the transcript was induced with no significant difference at 15 min of glucose
      induction; however, after 45 min, a clear difference in the level of expression
      was observed being 45% higher in WT than in sit4Delta strain. As at early time of
      induction, the HXT1 transcript was present but not the protein in the sit4Delta
      strain we analyzed association of HXT1 with ribosomes, which revealed a
      significant difference in the association profile; in the mutant strain, the HXT1
      transcript associated with a larger set of ribosomal fractions than it did in the
      WT strain, suggesting also a partial defect in protein synthesis. Overexpression
      of the translation initiation factor TIF2/eIF4A led to an increase in Hxt1p
      abundance in the WT strain only. It was concluded that Sit4p ensures that HXT1
      transcript is efficiently transcribed and translated thus increasing protein
      levels of Hxt1p when high glucose levels are present.

PMID- 22882631
TI  - Ileosigmoid knotting: clinical appearance of 73 cases over 45.5 years.
AB  - BACKGROUND: Ileosigmoid knotting (ISK) is the wrapping of the ileum around the
      base of the sigmoid colon. The aim of this study was to investigate the clinical
      outcomes of 73 patients with ISK over 45.5 years. METHODS: The clinical records
      were reviewed retrospectively. RESULTS: The age range was 7-92 years (mean 46.7
      years), and 54 patients (74.0%) were male. Forty-two patients (57.5%) experienced
      shock. The symptom duration range was 12-120 h (mean 46.5 h). The most common
      clinical features were abdominal pain and tenderness in 73 patients (100.0%),
      obstipation in 72 patients (98.6%), distention in 70 patients (95.9%) and
      vomiting in 61 patients (83.6%). The rate of correct diagnosis was 4.1% when
      based on clinical and X-ray findings (3/73) and 100.0% when based on computed
      tomography or magnetic resonance imaging findings (4/4 and 2/2, respectively).
      The diagnosis of ISK was confirmed by surgery in all cases. CONCLUSION: ISK is a
      rare disease that occurs most commonly in adult men. The disease is generally
      associated with shock, and the clinical features generally present as a
      mechanical bowel obstruction. Although X-rays may aid diagnosis, computed
      tomography and magnetic resonance imaging are more reliable diagnostic tools.
      However, the diagnosis is made at laparotomy in some cases.

PMID- 22882632
TI  - Assessment of the effects of adjunctive gabapentin on postoperative pain after
      intervertebral disc surgery in dogs.
AB  - OBJECTIVE: To assess the effect of adjunctive gabapentin (GBP) on pain after
      thoracolumbar intervertebral disc surgery in dogs. STUDY DESIGN: Prospective,
      randomized, controlled, clinical, 'blinded' trial. ANIMALS: Sixty-three client
      owned dogs undergoing hemilaminectomy METHODS: Dogs were assigned to two
      treatment groups. The GBP group received gabapentin 10 mg kg(-1) orally every 12
      hours starting before anaesthesia; the placebo (P) group received empty gelatin
      capsules. Background analgesia was initiated with intravenous levomethadone 0.6
      mg kg(-1) (as the combination 'L-Polamivet) at anaesthesia induction, followed by
      a fentanyl patch and levomethadone 0.2 mg kg(-1) subcutaneously every 8 hours for
      24 hours. Pain was assessed by the short form of the Glasgow Composite Measure
      Pain Score (CMPS-SF) without the gait category, and by a Visual Analogue Scale
      (VAS). Serum GBP concentrations and cortisol concentrations were measured.
      Statistical analyses utilized chi square test, Kolmogorov-Smirnov test, two-way
      analysis of variances for repeated measurements, Wilcoxon test and Friedmann test
      as relevant. Correlations were tested by Spearman's and Pearson's correlation
      coefficient. p < 0.05 was considered significant. RESULTS: Median CMPS-SF was
      lower in group GBP than in group P on days 0.5, 1, 4 and 5. However, CMPS-SF and
      VAS were not significantly different between groups. Both pain scores decreased
      significantly over time. Cortisol concentrations were not significantly different
      between groups. Minimum serum concentrations of GBP fell below the detection
      limit of 1 MUg mL(-1) in 6 of 29 and 7 of 28 dogs at 24 and 72 hours,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: 10 mg kg(-1) GBP orally twice a
      day did not result in a detectable reduction in pain behaviour compared to
      background opioid analgesia alone, although a trend to lower pain levels (p <
      0.1) was present. Further studies are needed to determine if this is related to
      effective background analgesia or an ineffective dose of GBP.

PMID- 22882633
TI  - Significance of liver histology in HBsAg-positive, IgM anti-HBc-negative acute
      hepatitis B virus-related hepatitis.
AB  - AIMS: The natural course of HBsAg-positive, IgM anti-HBc-negative acute hepatitis
      B virus (HBV)-related hepatitis is unclear. The aim of this study was to evaluate
      the prognostic significance of histological features and hepatic expression of
      HBV antigens in such patients. METHODS AND RESULTS: Fifty patients with HBsAg
      positive, IgM anti-HBc-negative acute hepatitis B who underwent liver biopsy
      during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16),
      persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n =
      25)]. Twenty-six cases had features of typical acute hepatitis only (group A),
      and 24 cases had changes suggesting pre-existing chronic hepatitis (group B).
      HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than
      in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of
      patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was
      significantly more frequent in group A than in group B (52% versus 0%, P <
      0.001), and in cases without rather than with immunohistochemical expression of
      HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed
      in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis,
      respectively (P < 0.034). CONCLUSIONS: Histological information is very important
      for the prognosis of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B.
      HBeAg seroconversion with underlying typical acute hepatitis changes of mild to
      moderate severity without hepatic expression of HBV antigens strongly predicts
      subsequent HBsAg loss.

PMID- 22882634
TI  - Ridge preservation at implants installed immediately after molar extraction. An
      experimental study in the dog.
AB  - AIM: To evaluate the influence of deproteinized bovine bone mineral (DBBM), in
      conjunction with a collagen membrane, on bone resorption at implants installed in
      a lingual position immediately into extraction sockets with horizontal residual
      buccal defects >2.0 mm. MATERIAL & METHODS: The pulp tissue of the mesial roots
      of (1) M(1)  was removed in six Labrador dogs, and the root canals were filled
      with gutta-percha and cement. Flaps were elevated. The molars were hemi-sectioned
      and the distal roots removed. Implants were installed in a lingual position and
      with the shoulder flush with the buccal bony crest. After installation, defects
      of about 2.5 and 2.7 mm in width resulted at the buccal aspects of the test and
      control sites, respectively. Only in the left site (test), deproteinized bovine
      bone mineral (DBBM) particles were placed into the defect concomitantly with the
      placement of a collagen membrane. On the control sites, no biomaterials were
      applied. A non-submerged healing was allowed. RESULTS: After 3 months of healing,
      one control implant was not integrated and was excluded from the analysis,
      together with the contralateral test implant. All remaining implants were
      integrated into mature bone. The buccal alveolar bony crest was resorbed more at
      the test compared with the control sites, 2.2 +/- 0.9 mm and 1.5 +/- 1.3 mm,
      respectively. The vertical resorption of the lingual plate was 1.6 +/- 1.5 mm and
      1.5 +/- 1.1 mm at the test and control sites, respectively. Only small residual
      DBBM particles were found at the test sites (1.4%). CONCLUSION: The use of DBBM
      particles to fill buccal defects of >=2.5 mm at implants installed immediately
      into alveolar extraction sockets did not preserve the buccal bony wall.

PMID- 22882635
TI  - Masticatory muscle disorders diagnostic criteria: the American Academy of
      Orofacial Pain versus the research diagnostic criteria/temporomandibular
      disorders (RDC/TMD).
AB  - In this study, relevant cases were retrospectively reviewed to identify patients
      who were diagnosed as suffering from myofascial pain only according to the
      research diagnostic criteria/temporomandibular disorders (RDC/TMD) criteria, in
      order to examine whether or not they could fulfil the American Academy of
      Orofacial Pain (AAOP) diagnostic criteria for TMD-related masticatory muscle
      disorders. One hundred and twenty-seven patients, diagnosed according to the
      RDC/TMD criteria as having myofascial pain with or without limited jaw opening
      only, were allocated to two groups according to their answers to the RDC/TMD 'jaw
      disability checklist'. The two groups were compared for Axis I and II data taken
      from the RDC/TMD questionnaire. Thirty-eight of the patients (29.9%) did not
      associate their symptoms with jaw functions (e.g. chewing and yawning). This
      group was characterised by increased range of motion (ROM) and older average age.
      The AAOP diagnostic criteria for TMD require pain on function in all subtypes of
      TMD-related muscle disorders. An association between pain and jaw function is
      common and research is needed to determine whether this should be categorised
      differently to muscle pain unrelated to jaw function. There may well be different
      pathophysiological mechanisms and consequently different management strategies
      for these two pain conditions.

PMID- 22882636
TI  - Empathy and values as predictors of care development.
AB  - This study investigates values and affective empathy as predictors for care-based
      moral development. Fifty-three students from a university of applied sciences
      were interviewed with Skoe's Ethic of Care Interview at the beginning of their
      studies and two years later. Value priorities were measured by Schwartz et al.'s
      Portrait Value Questionnaire, empathy variables by Davis' Interpersonal
      Reactivity Index, and feelings of sympathy were rated using a real-life moral
      conflict. The results showed that students in care-oriented fields progressed in
      care reasoning. Real-life sympathy and the value of self-direction positively
      predicted development in care reasoning, whereas personal distress was a negative
      predictor. The results indicate that care-based moral development is more closely
      connected with affective empathy than personal values. Individuals who feel
      empathy for others, and who prefer independent thinking and action, achieve the
      greatest gains in care development. In conclusion, educators should encourage
      students' empathy and moral reasoning in authentic moral conflicts.

PMID- 22882637
TI  - Liver graft volumetric changes after living donor liver transplantation with
      segment 2 graft for small infants.
AB  - LT for small infants weighing <5 kg with liver failure might require innovative
      techniques for size reduction and transplantation of small grafts to avoid large
      for-size graft, but little is known about post-transplant graft volumetric
      changes. Five of 172 children who underwent LDLT received monosegment or reduced
      monosegment grafts using a modified Couinaud's segment II (S2) graft for LDLT.
      Serial CT was used to evaluate the changes in the GV and other factors before
      LDLT and one and three months after LDLT. The shape of these grafts was
      classified into an OL type and an LL type. The GV increased in all patients one
      month after LDLT, whereas the GV decreased three months after LDLT in OL in
      comparison with one month after LDLT. The GRWR of the OL type has tended to
      decrease at three months, whereas the LL type showed a continuous increase with
      time, but finally they had adapted graft size for their body size. In conclusion,
      the volume of S2 grafts after LDLT had unique changes toward the ideal volume for
      the child weight when they received the appropriate liver volume.

PMID- 22882638
TI  - High incidence of rhesus enteric calicivirus infections and diarrhea in captive
      juvenile macaques: a likely association.
AB  - BACKGROUND: The rhesus enteric caliciviruses (ReCVs) were recently described.
      METHODS: Prevalence of ReCV antibodies was tested in six species of captive non
      human primates. RESULTS: High ReCV seroprevalence was revealed in rhesus and
      cynomolgus macaques. CONCLUSIONS: High rates of ReCV seroprevalence and diarrhea
      in juvenile macaques suggest that ReCVs may play a role in morbidity.

PMID- 22882639
TI  - Changes in tissue oxygenation following caudal epidural blockade in infants and
      children.
AB  - BACKGROUND: Adequate tissue oxygenation is required for effective white blood
      cell function and bactericidal activity. Decreased tissue oxygenation has been
      shown to be a risk factor for perioperative wound infections. Regional anesthetic
      techniques result in a functional sympathetic block and may increase tissue
      oxygenation. The purpose of the current study is to prospectively evaluate
      changes in tissue oxygenation using a non-invasive near-infrared spectroscopy
      (NIRS) device following caudal epidural block in infants and children. METHODS:
      Following standard anesthetic induction and general anesthesia with an
      endotracheal tube or laryngeal mask airway, the NIRS sensors were placed on two
      sites. One sensor was placed at a site affected by the caudal block (lower
      extremity), and the other sensor was placed on the arm, a site unaffected by the
      caudal block (upper extremity). The NIRS value was recorded at baseline and then
      again at 15, 30, and 45 min after the block. The caudal block was performed,
      after anesthetic induction and NIRS sensor placement, using bupivacaine 0.25%
      with epinephrine 1 : 200,000 or ropivacaine 0.2% with epinephrine 1 : 200,000 at
      a dose of 1 ml . kg(-1). The inspired oxygen concentration after induction was
      held constant at 30%, and anesthesia was maintained with sevoflurane at 1 MAC. No
      other pharmacologic agents were administered. RESULTS: Following the caudal
      epidural block, there was a statistically significant increase in the tissue
      oxygenation from the affected site. The NIRS value increased from a baseline of
      83 +/- 4 to 87 +/- 3 at 15 min (P = 0.0001 vs baseline), 88 +/- 4 at 30 min (P <
      0.0001 vs baseline), and 87 +/- 4 at 45 min (P < 0.0001 vs baseline). No change
      was noted on the unaffected site (upper extremity). CONCLUSION: There was a
      statistically significant increase in tissue oxygenation as measured by NIRS
      following caudal anesthesia in infants and children. Although the magnitude of
      the change was less, this study confirms the results of previous studies in
      adults showing an increase in tissue oxygenation following regional blockade.

PMID- 22882640
TI  - Preliminary success using hydrogen peroxide to treat Atlantic salmon, Salmo salar
      L., affected with experimentally induced amoebic gill disease (AGD).
AB  - Currently, the only effective and commercially used treatment for amoebic gill
      disease (AGD) in farmed Tasmanian Atlantic salmon is freshwater bathing. Hydrogen
      peroxide (H2O2), commonly used throughout the aquaculture industry for a range of
      topical skin and gill infections, was trialled in vitro and in vivo to ascertain
      its potential as an alternative treatment against AGD. Under in vitro conditions,
      trophozoites of Neoparamoeba perurans were exposed to three concentrations of
      H2O2 in sea water (500, 1000 and 1500 mg L-1) over four durations (10, 20, 30 and
      60 min) each at two temperatures (12 and 18  degrees C). Trophozoite viability
      was assessed immediately post-exposure and after 24 h. A concentration/duration
      combination of 1000 mg L-1 for >10 min demonstrated potent amoebicidal activity.
      Subsequently, Atlantic salmon mildly affected with experimentally induced AGD
      were treated with H2O2 at 12 and 18  degrees C for 15 min at 1250 mg L-1 and
      their re-infection rate was compared to freshwater-treated fish over 21 days.
      Significant differences in the percentage of filaments affected with hyperplastic
      lesions (in association with amoebae) and plasma osmolality were noted between
      treatment groups immediately post-bath. However, the results were largely
      equivocal in terms of disease resolution over a 3-week period following
      treatment. These data suggest that H2O2 treatment in sea water successfully
      ameliorated a clinically light case of AGD under laboratory conditions.

PMID- 22882641
TI  - Fatty liver: cause or consequence.

PMID- 22882643
TI  - Dynamic skin changes of acute radiation dermatitis revealed by in vivo
      reflectance confocal microscopy.
AB  - BACKGROUND: A better knowledge of the dynamic biological changes that the skin
      undergoes in response to ionizing radiation is advisable to improve the
      management of radiation dermatitis, allowing selection of patients needing
      treatment or close monitoring. OBJECTIVE: To describe the evolution of the skin
      in response to ionizing radiation through the reflectance confocal microscopy
      (RCM) features of acute radiation dermatitis. METHODS: In this prospective
      descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed
      with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included
      in the study through consecutive sampling. Clinical, dermoscopic and RCM
      evaluation of the skin were performed prior to treatment and on days 1, 15, 30
      and 45 after radiotherapy. RESULTS: While clinical features of radiation
      dermatitis emerged after 30 days on average, histopathological changes were
      detectable by RCM after a mean time of 15 days. The main RCM features included
      initial appearance of spongiosis, exocytosis and inflammatory cells followed by
      the presence of dendritic-shaped cells, 'streaming-like figures', 'broken
      geographic papillae', epidermal architectural disarray, effacement of rete
      ridges, melanophages and, finally, hyperpigmentation of the basal layer.
      CONCLUSIONS: RCM may safely detect the dynamic biological changes that the skin
      undergoes in response to ionizing radiation, even before than clinical onset of
      acute radiation dermatitis. Therefore, RCM may be useful to make an early and non
      invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early
      selection of patients needing treatment or close monitoring and avoiding skin
      biopsies.

PMID- 22882644
TI  - Medial humeral epicondylitis in cats.
AB  - OBJECTIVE: To describe medial humeral epicondylitis in cats based on
      radiographic, anatomic, and histologic observations. STUDY DESIGN: Prospective
      cohort study. ANIMALS: Feline cadavers (n = 60). METHODS: Extended craniocaudal,
      and extended and flexed mediolateral radiographic projections were taken of both
      elbows of 60 consecutive European shorthair cats that died or were euthanatized.
      Elbows with new bone formation at the medial epicondyle were dissected and
      embedded in methyl-methacrylate (MMA). For comparison, both elbows of a cat with
      no radiographic changes were prepared in a similar manner. Sections of the MMA
      blocks were Giemsa stained and examined with light microscopy. RESULTS: Bilateral
      new bone formation was identified radiographically at the medial aspect of the
      humeral epicondyle in 6 cats (10%). All of these cats had mineral deposition in
      the humeral head of the flexor carpi ulnaris muscle. Other findings were
      cartilage damage (n = 3 cats), an additional loose medial joint body (1), and
      tendinosis (3). The ulnar nerve was flattened and displaced caudally, and signs
      of chronic epineural fibrosis were present in 2 severely affected cats.
      CONCLUSIONS: Ten percent of this feline population had radiographic evidence of
      medial humeral epicondylitis with chronic degeneration, mineralization, and
      metaplastic bone formation in damaged fibrillar matrix involving the origin of
      the humeral head of the flexor carpi ulnaris muscle. New bone formation caused
      displacement and compression of the ulnar nerve in severely affected elbows.
      Based on our findings, medial humeral epicondylitis appears to be a common
      disorder in cats with potential clinical sequelae.

PMID- 22882645
TI  - Nurses' sociodemographic background and assessments of individualized care.
AB  - AIM: The aim of this study was to explore the association between nurses'
      characteristics (educational level, country, work title, gender, type of work,
      age, and length of working experience) and their assessments of individualized
      care. DESIGN: A cross-sectional comparative survey using questionnaires was
      employed to sample nurses from seven countries. METHODS: Data were collected from
      orthopedic and trauma nurses from Cyprus, Finland, Greece, Portugal, Sweden,
      Turkey, and the United States (N= 1,163, response rate 70%) using the
      Individualized Care Scale-Nurse (ICS-Nurse) and a sociodemographic questionnaire
      in 2008. Data were analyzed using descriptive statistics and general linear
      models. RESULTS: When compared with practical nurses, registered nurses, length
      of working experience, and the country of the nurses were associated with
      assessments of the support of patient individuality in specific nursing
      activities (ICS-A-Nurse) and country assessments of individuality in the care
      provided (ICS-B-Nurse). The background and experience within nursing teams
      together with the country affect the delivery of individualized care.
      CONCLUSIONS: Overall, our findings suggest that nurses' personal attributes have
      important effects on their assessments of individualized nursing care that will
      be useful when making context-dependent recruitment decisions. CLINICAL
      RELEVANCE: The characteristics of nurses contribute to the care delivered in
      healthcare organizations. Recognition of these nurse-related factors may help
      nurse leaders in the development and management of clinical practice.

PMID- 22882646
TI  - The effects of adjunctive metronidazole plus amoxicillin in the treatment of
      generalized aggressive periodontitis: a 1-year double-blinded, placebo
      controlled, randomized clinical trial.
AB  - AIM: To evaluate the clinical effects of the adjunctive use of metronidazole
      (MTZ) and amoxicillin (AMX) in the treatment of generalized aggressive
      periodontitis (GAgP). METHODS: Thirty subjects were randomly assigned to receive
      scaling and root planing (SRP) alone or combined with MTZ (400 mg/TID) and AMX
      (500 mg/TID) for 14 days. Subjects were clinically monitored at baseline, 6
      months and 1 year post-therapies. RESULTS: Both therapies led to a statistically
      significant improvement in all clinical parameters at 1 year post-therapy (p <
      0.05). Subjects receiving MTZ plus AMX exhibited the deepest reductions in mean
      probing depth (PD) and gain in clinical attachment between baseline and 1 year
      post-therapy in the full-mouth analysis and in initially intermediate (PD 4-6 mm)
      and deep (PD >= 7 mm) sites (p < 0.01). In addition, the antibiotic group
      presented lower mean number of residual sites with PD >= 5 or 6 mm as well as
      fewer subjects still presenting nine or more sites with PD >= 5 mm or three or
      more sites with PD >= 6 mm at the end of the study period. CONCLUSION: The non
      surgical treatment of GAgP is markedly improved by the adjunctive use of MTZ+AMX,
      up to 1 year post-treatment.

PMID- 22882647
TI  - Multi-length or 24 cm ureteric stent? A multicentre randomised comparison of
      stent-related symptoms using a validated questionnaire.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: One of the suggested
      factors for stent-related symptoms is that excess distal intravesical stent mass
      may cause bladder irritation. There is a lack of studies investigating this in a
      randomised controlled fashion using a validated questionnaire. This study
      compared two of the most commonly used length of stents (a 30 cm multi-length vs
      a 24 cm long stent) and showed no significance difference in stent-related
      symptoms in patients with either of these stents. OBJECTIVE: To investigate
      whether excessive redundant intravesical stent component contributes to the
      severity of stent-related symptoms in patients with a ureteric stent. We compared
      stent-related symptoms in patients who had either a standard 24 cm or multi
      length ureteric stent. PATIENTS AND METHODS: In all, 162 patients with upper
      urinary tract calculi requiring ureteric stent insertion were randomised to
      receive either a 6 F * 24 cm Contour(TM) or multi-length 6 F * 22-30 cm Contour
      VL(TM) stent. Patients were requested to complete the validated Bristol Ureteric
      Stent Symptom Questionnaire (USSQ) at 1 and 4 weeks after stent insertion and 4
      weeks after removal. The mean scores for each domain of the USSQ for both groups
      were compared using the Student's t-test. Any adverse events, e.g. stent
      migration, early removal of stent due to stent-related symptoms and failure of
      stent insertion, were also recorded. RESULTS: In all, 153 patients who had
      successful stent insertion were requested to complete the USSQ and 74% of
      patients returned at least the week 1 questionnaire. At 1 and 4 weeks with the
      stent in situ, comparison of the mean scores showed no significant difference in
      urinary symptoms, pain, general health, work performance, sexual dysfunction and
      number of days patients stayed in bed or reduced their routine activities. Three
      (2%) patients had their stent removed early due to stent-related symptoms and
      five (3%) had failed stent insertion. CONCLUSIONS: This study did not find any
      difference in symptoms between the 24 cm or multi-length Contour stents. However,
      the study was not powered to detect small differences particularly for the pain
      symptom domain. Stents should only be used sparingly and the stent dwell-time
      should be minimised.

PMID- 22882648
TI  - Recent insights into the diversity, frequency and ecological roles of phenazines
      in fluorescent Pseudomonas spp.
AB  - Phenazine compounds represent a large class of bacterial metabolites that are
      produced by some fluorescent Pseudomonas spp. and a few other bacterial genera.
      Phenazines were first noted in the scientific literature over 100 years ago, but
      for a long time were considered to be pigments of uncertain function. Following
      evidence that phenazines act as virulence factors in the opportunistic human and
      animal pathogen Pseudomonas aeruginosa and are actively involved in the
      suppression of plant pathogens, interest in these compounds has broadened to
      include investigations of their genetics, biosynthesis, activity as electron
      shuttles, and contribution to the ecology and physiology of the cells that
      produce them. This minireview highlights some recent and exciting insights into
      the diversity, frequency and ecological roles of phenazines produced by
      fluorescent Pseudomonas spp.

PMID- 22882649
TI  - Wild Plum: novel blue fluorescent compounds capable of luminosity restoration in
      sun-exposed skin.
AB  - BACKGROUND: Novel, blue fluorescent solids referred to as Wild Plum compounds can
      camouflage skin imperfections when incorporated into cosmetic products. We
      evaluated the relationship between sun exposure and skin fluorescence and
      determined if the application of Wild Plum formulations could restore lost
      fluorescence without harming the skin. METHODS: The forehead skin of two groups
      of volunteers of mixed gender and age was examined for fluorescence and redness.
      In addition, subjects answered questions describing any adverse sensations they
      experienced after their skin was exposed to Wild Plum formulations for extended
      periods of time. RESULTS: Fluorescence measurements of both solar and non-solar
      skin indicated that repeated sun exposure causes a loss of skin fluorescence.
      Application of Wild Plum formulations caused an increase in skin fluorescence at
      all concentrations, restoring solar skin fluorescence to values well beyond that
      of non-solar skin. Photo analysis and interview questions indicated that these
      formulations did not cause any symptoms of irritancy. CONCLUSION: Wild Plum
      compounds have the ability to restore fluorescence of solar skin to a level
      significantly higher than that associated with non-solar skin. Skin appears more
      luminous and therefore more youthful. This fluorescence restoration is achieved
      at relatively low concentrations, without any harmful side effects.

PMID- 22882650
TI  - Prevalence and significance of Hepatitis B reverse transcriptase mutants in
      different disease stages of untreated patients.
AB  - AIMS: Hepatitis B virus (HBV) reverse transcriptase (RT) mutants, which have not
      been well characterized according to different disease stages. This study aimed
      to characterize the profiles of naturally occurring mutations in the HBV RT
      region and their associated clinical outcomes. METHODS: HBV RT region mutations
      and genotypes were determined by PCR-direct sequencing and compared with p
      distance model. RESULTS: Among 467 consecutive eligible patients (262 chronic
      hepatitis B patients, 105 cirrhotic patients and 100 hepatocellular carcinoma
      patients), the nucleos(t)ide analogues-related mutations (rtI169T, rtV173L,
      rtL180M, rtA181T, rtS202C, rtM204I/V, rtN236T) were found. The p-distance value
      reached a peak in the age of 20-30 years in the CHB patients and in the age of 40
      45 years in the cirrhotic patients and hepatocellular carcinoma patients. The
      naturally occurring mutation, rtS106C mutation was higher in chronic hepatitis B
      patients (14/100, 14.0%) and cirrhotic patients (14/100, 14.0%) than that in
      hepatocellular carcinoma patients (4/100, 4.0%, P = 0.013). And the rtD134E/G/N/S
      mutations were also higher in chronic hepatitis B patients (22/100, 22.0%) and
      cirrhotic patients (21/100, 21.0%) than that in hepatocellular carcinoma patients
      (10/100, 10.0%, P = 0.021 and P = 0.032 respectively). The mutation frequencies
      in A-B interdomain were higher in cirrhotic patients (101/1900, 5.3%) than that
      in hepatocellular carcinoma patients (68/1900, 3.6%) (P = 0.009). CONCLUSIONS:
      The nucleos(t)ide analogues-related mutations do exist in treatment naive
      patients with different disease stages. rtS106C, rtD134E/G/N/S and A-B
      interdomain mutations may be associated with necro-inflammation, immune response
      and cirrhosis development at ages older than 40.

PMID- 22882651
TI  - Mitochondrial type 2C protein phosphatases CaPtc5p, CaPtc6p, and CaPtc7p play
      vital roles in cellular responses to antifungal drugs and cadmium in Candida
      albicans.
AB  - Type 2C protein phosphatases (PP2C) are monomeric enzymes that require magnesium
      or manganese ions for their activities. There are seven PP2C genes in Candida
      albicans. Here, we demonstrate that CaPTC5 encodes a mitochondrial PP2C enzyme.
      Expression of CaPTC5 transcripts remains constant during the serum-induced hyphal
      development. Deletion of CaPTC5 does not affect the in vitro filamentation but
      renders C. albicans cells sensitive to terbinafine and cadmium, and this
      sensitivity is complemented by the Saccharomyces cerevisiae ScPTC5. Deletion of
      CaPTC6 does not have any additive effect on, but deletion of CaPTC7 blocks, the
      terbinafine sensitivity owing to deletion of CaPTC5. In addition, we have shown
      that deletion of CaPTC6 also renders C. albicans cells sensitive to cadmium,
      while deletion of CaPTC7 leads to a high cadmium tolerance, and this tolerance is
      abolished by further deletion of CaPTC5 or CaPTC6. Furthermore, double deletion
      of CaPTC6 and CaPTC7 renders C. albicans cells more tolerant to azoles, but
      deletion of CaPTC5 and CaPTC7 slightly increases the azole sensitivity of C.
      albicans cells. Our results demonstrate that three mitochondrial PP2C genes
      CaPTC5, CaPTC6 and CaPTC7 interact differentially in the response of C. albicans
      cells to antifungal drugs and cadmium.

PMID- 22882652
TI  - Species, developmental stage and infection with microbial pathogens of engorged
      ticks removed from dogs and questing ticks.
AB  - Research into tick-borne diseases implies vector sampling and the detection and
      identification of microbial pathogens. Ticks were collected simultaneously from
      dogs that had been exposed to tick bites and by flagging the ground in the area
      in which the dogs had been exposed. In total, 200 ticks were sampled, of which
      104 came from dogs and 96 were collected by flagging. These ticks were
      subsequently examined for DNA of Borrelia burgdorferi sensu lato, Anaplasma
      phagocytophilum, Rickettsia spp. and Babesia canis. A mixed sample of adult ticks
      and nymphs of Ixodes ricinus (Ixodida: Ixodidae) and Haemaphysalis concinna
      (Ixodida: Ixodidae) was obtained by flagging. Female I. ricinus and adult
      Dermacentor reticulatus (Ixodida: Ixodidae) ticks dominated the engorged ticks
      removed from dogs. Rickettsia spp. were detected in 17.0% of the examined ticks,
      A. phagocytophilum in 3.5%, B. canis in 1.5%, and B. burgdorferi s.l. in 16.0%.
      Ticks with multiple infections were found only among the flagging sample. The
      ticks removed from the dogs included 22 infected ticks, whereas the flagging
      sample included 44 infected ticks. The results showed that the method for
      collecting ticks influences the species composition of the sample and enables the
      detection of a different pattern of pathogens. Sampling strategies should be
      taken into consideration when interpreting studies on tick-borne pathogens.

PMID- 22882653
TI  - Recombinant protein yield in rice seed is enhanced by specific suppression of
      endogenous seed proteins at the same deposit site.
AB  - Human IL-10 (hIL-10) is a therapeutic treatment candidate for inflammatory
      allergy and autoimmune diseases. Rice seed-produced IL-10 can be effectively
      delivered directly to gut-associated lymphoreticular tissue (GALT) via bio
      encapsulation. Previously, the codon-optimized hIL-10 gene was expressed in
      transgenic rice with the signal peptide and endoplasmic reticulum (ER) retention
      signal (KDEL) at its 5' and 3' ends, respectively, under the control of the
      endosperm-specific glutelin GluB-1 promoter. The resulting purified hIL-10 was
      biologically active. In this study, the yield of hIL-10 in transgenic rice seed
      was improved. This protein accumulated at the intended deposition sites, which
      had been made vacant through the selective reduction, via RNA interference, of
      the endogenous seed storage proteins prolamins or glutelins. Upon suppression of
      prolamins that were sequestered into ER-derived protein bodies (PB-I), hIL-10
      accumulation increased approximately 3-fold as compared to rice seed with no such
      suppression and reached 219 MUg/grain. In contrast, reducing the majority of the
      glutelins stored in protein-storage vacuoles (PB-II) did not significantly affect
      the accumulation of hIL-10. Considering that hIL-10 is synthesized in the ER
      lumen and subsequently buds off in ER-derived granules called IL-10 granules in a
      manner similar to PB-Is, these results indicate that increases in the available
      deposition space for the desired recombinant proteins may be crucial for
      improvements in yield. Furthermore, efficient dimeric intermolecular formation of
      hIL-10 by inhibiting interaction with Cys-rich prolamins also contributed to the
      enhanced formation of IL-10 bodies. Higher yield of hIL-10 produced in rice seeds
      is expected to have broad application in the future.

PMID- 22882654
TI  - Use and misuse of multivariable approaches in interventional cardiology studies
      on drug-eluting stents: a systematic review.
AB  - AIMS:  Randomized clinical trials (RCTs) are the most reliable evidence, even if
      they require important resource and logistic efforts. Large, cost-free and real
      world datasets may be easily accessed yielding to observational studies, but such
      analyses often lead to problematic results in the absence of careful methods,
      especially from a statistic point of view. We aimed to appraise the performance
      of current multivariable approaches in the estimation of causal treatment and
      effects in studies focusing on drug-eluting stents (DES). METHODS AND RESULTS:
      Pertinent studies published in the literature were searched, selected,
      abstracted, and appraised for quality and validity features. Six studies with a
      logistic regression were included, all of them reporting more than 10 events for
      covariates and different length of follow-up, with an overall low risk of bias.
      Most of the 15 studies with a Cox proportional hazard analysis had a different
      follow-up, with less than 10 events for covariates, yielding an overall low or
      moderate risk of bias. Sixteen studies with propensity score were included: the
      most frequent method for variable selection was logistic regression, with
      underlying differences in follow-up and less than 10 events for covariate in most
      of them. Most frequently, calibration appraisal was not reported in the studies,
      on the contrary of discrimination appraisal, which was more frequently performed.
      In seventeen studies with propensity and matching, the latter was most commonly
      performed with a nearest neighbor-matching algorithm yet without appraisal in
      most of the studies of calibration or discrimination. Balance was evaluated in
      46% of the studies, being obtained for all variables in 48% of them. CONCLUSIONS:
      Better exploitation and methodological appraisal of multivariable analysis is
      needed to improve the clinical and research impact and reliability of
      nonrandomized studies.

PMID- 22882655
TI  - Ways of regulating one's drinking: a factor analysis of a Finnish general
      population sample.
AB  - INTRODUCTION AND AIMS: This article studies the various ways of regulating
      drinking used by Finns and how these vary between men and women, and in different
      groups of age, educational attainment and alcohol consumption. DESIGN AND
      METHODS: The data consist of a cross-section of survey data collected in Finland
      in 2005. The response rate was 53%. The analysis was restricted to respondents
      who had used alcohol in the last 12 months and were between 15 and 71 years of
      age (n = 1013). A factor analysis was performed to discover underlying dimensions
      in the ways of regulation. In order to study the relationship between the ways of
      regulation and drinking habits, correlations and regression analyses were used.
      RESULTS: The ways of regulating one's drinking extracted to three factors which
      were named self-control, social control and external control. Self-control was
      the most common way of regulation. Stronger reliance on external control of
      drinking increased the probability of heavy alcohol use. DISCUSSION AND
      CONCLUSIONS: These survey results indicate that external control of drinking, for
      example the restriction of availability of alcohol, could have a greater impact
      on heavy drinking than on moderate drinking.

PMID- 22882657
TI  - How holistic are we? The role of narrative, storytelling and reflection in the
      development of holistic practice.

PMID- 22882656
TI  - Ovarian serous papillary carcinoma, metastatic to intramammary lymph-node mimic a
      primary breast carcinoma on RX mammography.

PMID- 22882658
TI  - Closing the regulatory regress: GMP accreditation in stem cell laboratories.
AB  - Contemporary biomedical research is conducted amidst regimes of national and
      transnational regulation. Regulation, like rules generally, cannot specify all
      the practicalities of their application. Regulations for biomedical research
      impose considerable constraints on laboratories and others. In principle, there
      is a never-ending regress whereby scientists have to provide increasingly more
      guarantees that protocols have been followed, standards reached and maintained,
      and rules adhered to. In practice, regulatory regress is not the actual outcome,
      as actors find ways of establishing closure for all practical purposes. Based on
      ethnographic case studies of two sites of biomedical work--the UK Stem Cell Bank
      and an anonymous laboratory working with primary human foetal material--this
      article documents the possibility of regulatory regress and strategies aimed at
      its closure.

PMID- 22882659
TI  - Insights into type IV pilus biogenesis and dynamics from genetic analysis of a C
      terminally tagged pilin: a role for O-linked glycosylation.
AB  - Type IV pili are surface organelles essential for pathogenicity of many Gram
      negative bacteria. In Neisseria gonorrhoeae, the major subunit of type IV pili,
      PilE, is a target of its general O-linked glycosylation system. This system
      modifies a diverse set of periplasmic and extracellular gonococcal proteins with
      a variable set of glycans. Here we show that expression of a particular hexa
      histidine-tagged PilE was associated with growth arrest. By studying intra- and
      extragenic suppressors, we found that this phenotype was dependent on pilus
      assembly and retraction. Based on these results, we developed a sensitive tool to
      identify factors with subtle effects on pilus dynamics. Using this approach, we
      found that glycan chain length has differential effects on the growth arrest that
      appears to be mediated at the level of pilin subunit-subunit interactions and
      bidirectional remodelling of pilin between its membrane-associated and assembled
      states. Gonococcal pilin glycosylation thus plays both an intracellular role in
      pilus dynamics and potential extracellular roles mediated through type IV pili.
      In addition to demonstrating the effect of glycosylation on pilus dynamics, the
      study provides a new way of identifying factors with less dramatic effects on
      processes involved in type IV pilus biogenesis.

PMID- 22882660
TI  - Time to computed tomography scanning for major trauma patients: the Australian
      reality.
AB  - BACKGROUND: Computed tomography (CT) can facilitate the diagnosis of life
      threatening injuries in polytrauma patients. Reported times to imaging vary
      widely, but it has been suggested that rapid whole body scanning improves
      mortality rates. The aim of this study was to determine the time to CT for severe
      polytrauma patients presenting to a level I trauma centre in Australia. METHODS:
      Retrospective audit of prospectively collected trauma registry data combined with
      electronic medical records. Inclusion criteria were trauma patients with injury
      severity score >=16 who underwent CT scanning over a 12-month period. Exclusion
      criteria were scans performed at regional centres or greater than 5 h after
      arrival. Time to commencement of CT was defined as time from arrival to the first
      CT image being recorded, and time to completion of CT as the time from arrival to
      recording the final CT image. Time in CT was defined as minutes between
      acquisition of the first and final images. RESULTS: Two hundred thirty-three
      eligible patients were admitted over the study period. CT acquisition times were
      median 76 min (interquartile range (IQR) 52-115) to commencement, 93 min (IQR 71
      129) to completion and time in CT 14 min (IQR 6-24). Time to completion was
      faster for isolated head scans, abbreviated injury scale head >3, intubated
      patients and those with subsequent fatal outcome. CONCLUSIONS: Although 93 min to
      completion of trauma CT scans is comparable with some international reports, it
      falls well behind centres who have demonstrated improved outcomes with CT
      scanning. Our results serve as a baseline to our and potentially other
      Australasian trauma centres to improve on this surrogate measure of trauma team
      efficacy.

PMID- 22882661
TI  - Long-term results of implant-supported over-dentures retained by double crowns: a
      practice-based retrospective study after minimally 10 years follow-up.
AB  - BACKGROUND: Different concepts regarding the number of implants and attachment
      systems for the preparation of implant-supported over-dentures (IODs) have been
      discussed. Nonetheless, long-term results for double-crown-retained IODs with an
      observational period of more than 10 years are still rare in the literature.
      OBJECTIVE: The aim of this practice-based study was to retrospectively evaluate
      the long-term clinical outcome (success/survival rates, technical/biological
      complications) of IODs retained by double crowns. MATERIAL AND METHODS: In a
      private practice, 36 non-smoking edentulous patients were restored between 1991
      and 2002 with double-crown-retained IODs supported by 2-6 implants. For the
      retrospective evaluation of implant and prosthetic survival (in-situ criterion)
      and success (event-free observational period), only those patients were included
      who regularly (at least once a year) participated in a professional maintenance
      programme and who had a functional period for the restoration of more than 10
      years. RESULTS: Twenty-two patients (12 Women/10 men, mean age 60.1 +/- 9.8
      years) with 89 implants supporting nine maxillary and 13 mandibulary dentures
      (mean number of implants/prosthesis = 4) met the inclusion criteria. The mean
      follow-up period was 14.1 +/- 2.8 years. One implant failed after 4.9 years
      (cumulative-survival rate: 98.9%). Seven implants in two patients showed peri
      implantitis (prevalence: patient-based = 9.1%/implant-based = 8%). Five dentures
      were renewed (prosthetic-survival rate 77.3% Maintenance procedures (i.e. screw
      loosening or acrylic fractures) were required at a rate of 0.31/year and patient.
      CONCLUSION: This study indicates that IODs retained with double crowns offer
      predictable long-term performance with a limited incidence of biological and
      technical complications.

PMID- 22882662
TI  - The relationship between the FFM and personality disorders in a personnel
      selection sample.
AB  - The relationships between the Five Factor Model (FFM) personality and personality
      disorders were investigated. A sample of real-life job applicants completed two
      personality questionnaires with different theoretical backgrounds in a
      psychological assessment center. The job applicants provided self-descriptions
      both on the FFM inventory and on a personality disorder trait inventory. A
      subsample of these candidates was interviewed by expert psychologists upon
      entrance to the assessment center. The psychologists assessed the same disorder
      traits of each target in job interviews. Both self-descriptions were used to
      predict the expert assessments. The results demonstrated considerable overlap
      between the FFM measures of normal and measures of abnormal personality in both
      samples and regardless of assessment method.

PMID- 22882663
TI  - Periodontal diseases and stress: a brief review.
AB  - Periodontal diseases are common chronic inflammatory diseases caused by
      pathogenic microorganisms colonising the subgingival area and inducing local and
      systemic elevations of pro-inflammatory cytokines resulting in tissue
      destruction. Apparition and evolution of periodontal diseases are influenced by
      many local or systemic risk factors. Psychological stress has been suggested as
      one of them and may negatively influence the outcome of periodontal treatment.
      However, mechanisms explaining the possible relationship between stress and
      increased susceptibility to periodontal disease remain poorly understood. Several
      stress markers are found in blood and saliva of patients with periodontal
      diseases and influence the development of periodontal diseases by several
      mechanisms including modifications of the inflammatory response and changes in
      the composition of the dental biofilm. The aim of this review is to provide an
      insight into the relationship between psychological stress and periodontal
      diseases.

PMID- 22882665
TI  - Post-kala-azar dermal leishmaniasis in visceral leishmaniasis-endemic communities
      in Bihar, India.
AB  - We assessed the prevalence of post-kala-azar dermal leishmaniasis (PKDL), a late
      cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL-endemic
      communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per
      10 000 individuals and 7.8 if probable cases were also considered. The clinical
      history and treatment of the post-kala-azar dermal leishmaniasis cases are
      discussed. 

PMID- 22882664
TI  - Mitigation of radiation induced pulmonary vascular injury by delayed treatment
      with captopril.
AB  - BACKGROUND AND OBJECTIVE: A single dose of 10 Gy radiation to the thorax of rats
      results in decreased total lung angiotensin-converting enzyme (ACE) activity,
      pulmonary artery distensibility and distal vascular density while increasing
      pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we
      evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE
      inhibitor captopril, to mitigate this pulmonary vascular damage. METHODS: Rats
      exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2
      months after exposure, during the development of radiation pneumonitis. Rats were
      treated, either immediately or 2 weeks after radiation exposure, with two doses
      of the ACE inhibitor, captopril, dissolved in their drinking water. To determine
      pulmonary vascular responses, we measured pulmonary haemodynamics, lung ACE
      activity, pulmonary arterial distensibility and peripheral vessel density.
      RESULTS: Captopril, given at a vasoactive, but not a lower dose, mitigated
      radiation-induced pulmonary vascular injury. More importantly, these beneficial
      effects were observed even if drug therapy was delayed for up to 2 weeks after
      exposure. CONCLUSIONS: Captopril resulted in a reduction in pulmonary vascular
      injury that supports its use as a radiomitigator after an unexpected radiological
      event such as a nuclear accident.

PMID- 22882666
TI  - Viral encephalopathy and retinopathy outbreak in restocking facilities of the
      endangered freshwater species, Salaria fluviatilis (Asso).

PMID- 22882667
TI  - Renal function and histology in children after small bowel transplantation.
AB  - CKD is a frequent long-term complication after SBTx. CNIs are a well-known
      factor, but probably not the only cause. We assessed the incidence, risk factors,
      and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and
      prednisone/TAC-based maintenance immunosuppression. Median follow-up was seven yr
      (3-21). A renal biopsy was performed in 14 patients, 1-18 yr post-SBTx. A reduced
      GFR was observed in 17 children (63%) during the follow-up with none requiring
      dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post
      transplant, and could occur with a normal mGFR. The dose of TAC was reduced by
      50% in 13 patients with CKD and/or significant kidney histological lesions, and
      six were also given MMF. This led to a significant improvement in renal function:
      mGFR normalized in eight patients and improved or stabilized in five. No
      rejection occurred. At last follow-up, 37% had CKD stage 2 and 15% had CKD stage
      3. In conclusion, CKD is frequent in children after SBTx and probably
      multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and
      should be further considered. The kidney histology helps in designing
      personalized immunosuppression strategies for patients.

PMID- 22882668
TI  - Understanding the burden of pneumococcal disease in adults.
AB  - Streptococcus pneumoniae causes different types of acute, invasive and non
      invasive clinical infections, being the most frequently detected pathogen
      responsible for community-acquired pneumonia. Pneumococcal pneumonia is
      accompanied by bacteraemia in 10-30% of cases. Streptococcus pneumoniae is
      gaining resistance to the in vitro activity of several antimicrobial agents and,
      even if questions remain regarding the clinical impact of this phenomenon, more
      and more reports indicate that antibiotic resistance can lead to more treatment
      failures if not higher mortality. Use of the 23-valent anti-pneumococcal vaccine
      appears to offer subpotimal protection against pneumococcal disease, particularly
      among high-risk adult populations. Vaccination against S. pneumoniae with new
      conjugate vaccines seems to be the most promising field for real improvement in
      the management of pneumococcal infections in adults.

PMID- 22882669
TI  - Angiomyolipoma of the liver: a reappraisal of morphological features and
      delineation of new characteristic histological features from the
      clinicopathological findings of 55 tumours in 47 patients.
AB  - AIMS: The aim of this study was to characterize and delineate the broad
      histological spectrum of hepatic angiomyolipoma (AML) and to obtain a better
      understanding of its clinicopathological diagnosis by reviewing a large series of
      AMLs. METHODS AND RESULTS: According to the proportions of three histological
      components, AML could be classified into 10 types; 36 of 55 tumours (65%) were
      classified as myomatous, eight as myoangiomatous, six as mixed (conventional),
      two as lipomatous, two as myolipomatous, and one as lipomyomatous. The morphology
      of smooth muscle cells (SMCs) in AML was quite variable, giving a wide variety of
      growth patterns. Fourteen (25%) of 55 tumours showed severe cellular atypia, and
      invasive growth of tumour cells was found in 69% of the tumours. However, except
      for two autopsy cases, all of the patients were in good health at follow-up,
      without metastases. Immunostaining for HMB-45 was positive in all cases. We found
      frequent lymphocyte infiltration, and the occasional presence of abnormally large
      blood vessels around the tumour at the tumour-background liver interface,
      features which have not been reported previously. CONCLUSIONS: The majority of
      hepatic AMLs were myomatous in type, showing variable cellular morphology and
      growth patterns. Cellular atypia and invasive growth were frequent, indicating
      that hepatic AMLs often show malignancy-like histological features. Although the
      majority of cases behave as benign tumours, AML should be considered to have
      uncertain malignant potential, and careful follow-up of patients is recommended.
      Immunostaining for HMB-45 is specific for AML, and establishes the diagnosis. The
      occasional presence of abnormally large blood vessels around the tumour may give
      new insights into the evaluation of findings from imaging.

PMID- 22882670
TI  - The evaluation of family impact of recessive dystrophic epidermolysis bullosa
      using the Italian version of the Family Dermatology Life Quality Index.
AB  - BACKGROUND: Severe skin diseases, such as epidermolysis bullosa (EB), may have a
      strong impact not only on patients but also on caregivers. A specific
      questionnaire evaluating the family impact of dermatological conditions has been
      created, the Family Dermatology Life Quality Index (FDLQI), but it has not yet
      been translated in Italian and validated. OBJECTIVE: To evaluate the burden of
      recessive dystrophic EB on family caregivers, using for the first time the
      Italian version of the FDLQI, and to validate the instrument. METHODS: Patients
      with recessive dystrophic EB participated in a postal survey enquiring about the
      burden of EB on family caregivers. They completed the Family Strain Questionnaire
      and the FDLQI and they marked on a silhouette of the human body the skin lesion
      distribution. RESULTS: Data on 62 family caregivers were collected. The overall
      mean FDLQI score was 9.8. The most frequently reported problems were the time
      spent on looking after the patient, emotional distress, physical well-being, and
      increased household expenditure. FDLQI scores were higher in family caregivers of
      patients between 10 and 20 years. The Italian FDLQI showed high internal
      consistency, construct and convergent validity. Factor analysis revealed the
      presence of one factor structure underlying the items of the FDLQI, which
      explained 51.5% of the total variance, very similar to the original questionnaire
      (55.8%). CONCLUSION: The Italian version of the FDLQI seems to be a useful tool
      to evaluate the impact of EB on family caregivers. Further studies are necessary
      to test this instrument in other dermatological conditions.

PMID- 22882671
TI  - Reye's or Reye's-like syndrome in western lowland gorilla (Gorilla gorilla
      gorilla).
AB  - BACKGROUND: A 15-year-old western lowland gorilla (Gorilla gorilla gorilla) died
      shortly after transfer to the North Carolina Zoo. METHODS: Complete blood count,
      serum biochemical analysis, and necropsy were performed. RESULTS: Combination of
      compatible clinical signs, biochemical and histopathological findings fulfilled
      all of the CDC definition criteria of Reye's or a Reye's like syndrome.
      CONCLUSIONS: This report describes a case of Reye's syndrome or Reye's-like
      syndrome in a non-human primate.

PMID- 22882672
TI  - The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national
      cohort of young sudden unexplained death cases.
AB  - INTRODUCTION: Sudden unexplained death account for one-third of all sudden
      natural deaths in the young (1-35 years). Hitherto, the prevalence of
      genopositive cases has primarily been based on deceased persons referred for
      postmortem genetic testing. These deaths potentially may represent the worst of
      cases, thus possibly overestimating the prevalence of potentially disease causing
      mutations in the 3 major long-QT syndrome (LQTS) genes in the general population.
      We therefore wanted to investigate the prevalence of mutations in an unselected
      population of sudden unexplained deaths in a nationwide setting. METHODS: DNA for
      genetic testing was available for 44 cases of sudden unexplained death in Denmark
      in the period 2000-2006 (equaling 33% of all cases of sudden unexplained death in
      the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro
      electrophysiological studies were performed on novel mutations. RESULTS: In
      total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding
      to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2
      and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro
      electrophysiological studies of P1177L SCN5A revealed an increased sustained
      current suggesting a LQTS phenotype. CONCLUSION: In a nationwide setting, the
      genetic investigation of an unselected population of sudden unexplained death
      cases aged 1-35 years finds a lower than expected number of mutations compared to
      referred populations previously reported. We therefore conclude that the
      prevalence of mutations in the 3 major LQTS associated genes may not be as
      abundant as previously estimated.

PMID- 22882673
TI  - A randomized, prospective study of efficacy and safety of oral tramadol in the
      management of post-herpetic neuralgia in patients from north India.
AB  - OBJECTIVE: To evaluate the safety and efficacy of oral tramadol therapy (50 to
      200 mg/day) in the treatment for post-herpetic neuralgia (PHN). METHODS: The
      study was a prospective, single-blind, non-responder vs. responder, randomized
      trial conducted in 100 outpatients of PHN after oral administration of tramadol
      for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14
      days of oral tramadol treatment were categorized as responders and those
      reporting < 50% pain relief were categorized as non-responders. Rescue analgesia
      was provided by the topical application of a cream consisting of the combination
      of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of
      both groups for at least 14 days, along with tramadol therapy. The rescue
      analgesia was extended to 4 weeks in patients of the non-responder group. The
      primary endpoints were measured using a numerical rating scale (NRS) at rest and
      with movement. Secondary endpoints included additional pain ratings such as
      global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI),
      daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF
      Questionnaire scores, patient and clinician ratings of global improvement. The 2
      groups were compared on the basis of pain intensity scores, encompassing primary
      as well as secondary endpoints, and QOL after 28 days of the treatment regimen.
      RESULTS: Pain intensity scores measured by NRS (at resting and with movement),
      NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying
      intervals in both the groups, but the magnitude of reduction was higher in
      responders than non-responders. A concomitant improvement (P < 0.001) was
      observed in GPE on days 3, 14, and 28 as compared to the respective baseline
      scores in both the groups. Although the WHO QOL-BREF scores showed significant (P
      < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups,
      the magnitude of improvement was higher in responders as compared to non
      responders. Significant improvement in pain intensity scores and QOL in non
      responders is mainly attributed to the use of rescue analgesia for 28 days rather
      than recommended tramadol therapy. CONCLUSIONS: Treatment with tramadol 50 to 200
      mg per day was associated with significant pain reduction in terms of enhanced
      pain relief, reduced sleep interference, greater global improvement, diminished
      side-effect profile, and improved QOL in PHN patients from North India. Further
      categorization of PHN patients may be helpful so that additional or alternative
      therapy may be prescribed to non-responders.

PMID- 22882674
TI  - Determinants of survival in patients receiving dialysis in Libya.
AB  - Maintenance dialysis is associated with reduced survival when compared with the
      general population. In Libya, information about outcomes on dialysis is scarce.
      This study, therefore, aimed to provide the first comprehensive analysis of
      survival in Libyan dialysis patients. This prospective multicenter study included
      all patients in Libya who had been receiving dialysis for >90 days in June 2009.
      Sociodemographic and clinical data were collected upon enrollment and survival
      status after 1 year was determined. Two thousand two hundred seventy-three
      patients in 38 dialysis centers were followed up for 1 year. The majority were
      receiving hemodialysis (98.8%). Sixty-seven patients were censored due to renal
      transplantation, and 46 patients were lost to follow-up. Thus, 2159 patients were
      followed up for 1 year. Four hundred fifty-eight deaths occurred, (crude annual
      mortality rate of 21.2%). Of these, 31% were due to ischemic heart disease, 16%
      cerebrovascular accidents, and 16% due to infection. Annual mortality rate was 0%
      to 70% in different dialysis centers. Best survival was in age group 25 to 34
      years. Binary logistic regression analysis identified age at onset of dialysis,
      physical dependency, diabetes, and predialysis urea as independent determinants
      of increased mortality. Patients receiving dialysis in Libya have a crude 1-year
      mortality rate similar to most developed countries, but the mean age of the
      dialysis population is much lower, and this outcome is thus relatively poor. As
      in most countries, cardiovascular disease and infection were the most common
      causes of death. Variation in mortality rates between different centers suggests
      that survival could be improved by promoting standardization of best practice.

PMID- 22882675
TI  - A perceptually oriented method for contrast enhancement and segmentation of
      dermoscopy images.
AB  - BACKGROUND/PURPOSE: Dermoscopy images often suffer from low contrast caused by
      different light conditions, which reduces the accuracy of lesion border
      detection. Accordingly for lesion recognition, automatic melanoma border
      detection (MBD) is an initial as well as crucial task. METHOD: In this article, a
      novel perceptually oriented approach for MBD is presented by combing region and
      edge-based segmentation techniques. The MBD system for color contrast and
      segmentation improvement consists of four main steps: first, the RGB dermoscopy
      image is transformed to CIE L*a*b* color space, lesion contrast is then enhanced
      by adjusting and mapping the intensity values of the lesion pixels in the
      specified range using the three channels of CIE L*a*b*, a hill-climbing algorithm
      is used later to detect region-of-interest (ROI) map in a perceptually oriented
      color space using color channels (L*,a*,b*) and finally, an adaptive thresholding
      is applied to determine the optimal lesion border. Manually drawn borders
      obtained from an experienced dermatologist are utilized as a ground truth for
      performance evaluation. RESULTS: The proposed MBD method is tested on a total of
      100 dermoscopy images. A comparative study with three state-of-the-art color and
      texture-based segmentation techniques (JSeg, dermatologists-like tumor area
      extraction: DTEA and region-based active contours: RAC), is also conducted to
      show the effectiveness of our MBD method using measures of true positive rate
      (TPR), false positive rate (FPR), and error probability (EP). Among different
      algorithms, our MBD algorithm achieved TPR of 94.25%, FPR of 3.56%, and EP of 4%.
      CONCLUSIONS: The proposed MBD approach is highly accurate to detect the lesion
      border area. The MBD software and sample of dermoscopy images can be downloaded
      at http://cs.ntu.edu.pk/research.php.

PMID- 22882676
TI  - Zoledronic acid in combination with serine/threonine phosphatase inhibitors
      induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer
      cell lines by decreasing the activities of PP1 and PP2A.
AB  - What's known on the subject? and What does the study add? Prostate cancer is the
      second most common cancer diagnosed among elderly men. Current standard of care
      with surgery, chemotherapy or radiation in prostate cancer patients are of
      limited efficacy, especially in the androgen refractory state of the disease, and
      unfortunately metastatic disease remains incurable. Skeletal metastases are the
      most common site for metastases for prostate cancer and bisphosphonates have been
      widely used for the treatment of morbidity due to skeletal related events.
      Zoledronic acid (ZA) is the most potent member of the nitrogen containing new
      generation bisphosphonate (N-BPs) family. Okadaic acid (OA) and Calyculin A (CA)
      are the most commonly used inhibitors of PP1 and 2A. OA, extracted from common
      black sponge Halachondria okaddai is a potent inhibitor of protein phosphatases,
      PP1 and PP2A, and CA was isolated from another marine sponge, Discodermia calyx.
      Therapies based on combinations of chemotherapeutics with phosphatase inhibitors
      that target signaling pathways within the cell with different mechanisms of
      action, may be useful for increasing therapeutic effect and also diminish toxic
      side effects by decreasing the doses of conventional chemotherapeutics. Although
      clinically well known, the in vitro effects of ZA on cancer cells and the
      underlying mechanisms are not well elucidated. In our previous studies, we have
      already shown anticancer effect of ZA in hormone-and drug refractory prostate
      cancer cells, PC-3 and DU-145. In addition to this, we have also shown that this
      anticancer effect may be augmented with some cytotoxic agents in prostate cancer.
      Now, in our present study, we have investigated whether ZA induced growth
      inhibition and apoptosis in PC-3 and DU-145 may be enhanced by the combination
      with CA or OA, through inhibition of serine/threonine phosphatases in prostate
      cancer cells. Both ZA/CA and ZA/OA combinations inhibited the cell viability of
      hormone-and drug refractory prostate cancer cells at in vivo achievable
      therapeutic concentrations. Moreover, a potentiation of the apoptotic effects of
      the combinations was also observed in the same experimental conditions. This is
      the first report of a synergistic combination of ZA with phosphatase inhibitors
      CA and OA which inhibits cell viability and induces apoptosis in human hormone
      and drug refractory prostate cancer cells. OBJECTIVES: * To investigate if the
      cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the
      addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA)
      and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3
      and DU-145. * To discover the effect of these combination treatments on
      phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells.
      MATERIALS AND METHODS: * An XTT cell viability assay was used to determine
      cytotoxicity. * Apoptosis was evaluated by enzyme-linked immunosorbent assay
      (ELISA) using a Cell Death Detection ELISA Plus Kit and verified by measuring
      caspase 3/7 enzyme activity. * The PP1 and PP2A enzyme activities were evaluated
      by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A
      proteins were then re-assessed by Western blot analysis. RESULTS: * Combination
      of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared
      with any agent alone in both PC-3 and DU-145 prostate cancer cells. * The
      combination of ZA with phosphatase inhibitors resulted in enhanced suppression of
      both PP1 and PP2A enzyme activity and protein levels, which was more overt with
      the ZA/CA combination. CONCLUSION: * Results from our study increase the
      translational potential of our in vitro findings and offer the basic rationale
      for the design of new combinatory strategies with ZA and phosphatase inhibitors
      for the treatment of prostate cancer, which may become resistant to conventional
      therapy.

PMID- 22882677
TI  - Periodontal pathogen load and increased antibody response to heat shock protein
      60 in patients with cardiovascular disease.
AB  - AIM: To determine the relationship between periodontal pathogen load and anti
      human heat shock protein 60 (hHSP60) antibodies in patients with established
      cardiovascular disease (CVD). MATERIALS AND METHODS: Participants were
      cardiovascular patients (n = 74) with a previous hospital admission for
      myocardial infarction. Concurrent periodontal pathogen load of Porphyromonas
      gingivalis, Fusobacterium nucleatum, Tannerella forsythia and Aggregatibacter
      actinomycetemcomitans was determined using quantitative real-time PCR. Serum
      antibodies to these pathogens, GroEL and hHSP60 were determined using an ELISA.
      RESULTS: There was a trend for increasing anti-hHSP60 antibody as the number of
      bacterial species increased. The strongest positive correlations were found
      between anti-hHSP60 levels and numbers of T. forsythia (r = 0.43; p < 0.001) and
      between anti-hHSP60 and anti-GroEL levels (r = 0.39; p = 0.001). Patients with
      extensive periodontal pocketing (>=4 mm) had higher numbers of P. gingivalis and
      T. forsythia (p < 0.05) and a higher subgingival pathogen load (p < 0.05) than
      patients with minimal pocketing (<=1 site >= 4 mm). They also had significantly
      elevated anti-hHSP60 levels (p < 0.05). Overall, the highest anti-hHSP60 levels
      were seen in patients with extensive periodontal pocketing and all four bacterial
      species. CONCLUSIONS: In cardiovascular patients, a greater burden of subgingival
      infection with increased levels of P. gingivalis and T. forsythia is associated
      with modestly higher anti-hHSP60 levels.

PMID- 22882678
TI  - Trends in drug use among gay and bisexual men in Sydney, Melbourne and
      Queensland, Australia.
AB  - INTRODUCTION AND AIMS: The findings of Australian drug surveys are typically not
      stratified by sexual orientation, despite the higher prevalence of drug use
      generally reported among gay and bisexual men. This paper aims to examine trends
      in drug use among gay and bisexual men in eastern Australia between 2004 and
      2011. DESIGN AND METHODS: Data from the cross-sectional, ongoing Gay Community
      Periodic Surveys (GCPS) were used to analyse drug trends among gay and bisexual
      men in Sydney, Melbourne and Queensland. Between 2004 and 2011, 45,273 eligible
      questionnaires were completed. RESULTS: There was a downward trend in recent drug
      use (previous 6 months) between 2004 and 2011 from 62.2% to 57.5%. However, this
      trend was not found among men in Queensland, bisexual men, men aged over 40 years
      or HIV-positive men. Club drug use peaked in 2006 (45.1%), before steadily
      declining to 32.4% in 2011. There were significant reductions in use of ecstasy,
      methamphetamine, ketamine and cannabis, increased use of cocaine, gamma
      hydroxybutyrate, erectile dysfunction medications, amyl nitrite and lysergic acid
      diethylamide, and no change in heroin use. Recent injecting drug use fluctuated
      over time but experienced an overall downward trend from 5.5% in 2004 to 4.0% in
      2011. DISCUSSION AND CONCLUSIONS: Drug use trends among gay and bisexual men in
      Australia are broadly consistent with downward and upward drug trends reported in
      other Australian drug surveys. The risks associated with drug use in this
      population and high rates of use supports the ongoing role of the GCPS in
      monitoring drug trends among homosexually active men.

PMID- 22882679
TI  - Complex evaluation of human monocyte-derived dendritic cells for cancer
      immunotherapy.
AB  - Dendritic cell (DC) immunotherapy is capable of generating tumour-specific immune
      responses. Different maturation strategies were previously tested to obtain DC
      capable of anti-cancer responses in vitro, usually with limited clinical benefit.
      Mutual comparison of currently used maturation strategies and subsequent complex
      evaluation of DC functions and their stimulatory capacity on T cells was
      performed in this study to optimize the DC vaccination strategy for further
      clinical application. DC were generated from monocytes using granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, pulsed with
      whole tumour cell lysate and then matured with one of five selected maturation
      strategies or cultured without additional maturation stimulus. DC were
      characterized with regard to their surface marker expression, cytokine profiles,
      migratory capacity, allogeneic and autologous T cell stimulatory capacity as well
      as their specific cytotoxicity against tumour antigens. We were able to
      demonstrate extensive variability among different maturation strategies currently
      used in DC immunotherapeutic protocols that may at least partially explain
      limited clinical benefit of some clinical trials with such DC. We identified DC
      matured with interferon-gamma and lipopolysaccharide as the most attractive
      candidate for future clinical trials in cancer immunotherapy.

PMID- 22882680
TI  - Clinical utility of array comparative genomic hybridisation for prenatal
      diagnosis: a cohort study of 3171 pregnancies.

PMID- 22882683
TI  - Glucose challenge test for detecting gestational diabetes mellitus: a systematic
      review.

PMID- 22882684
TI  - Classification of episiotomy: towards a standardisation of terminology.

PMID- 22882689
TI  - Use of multiple linear regression and logistic regression models to investigate
      changes in birthweight for term singleton infants in Scotland.
AB  - AIM: To illustrate the use of regression and logistic regression models to
      investigate changes over time in size of babies particularly in relation to
      social deprivation, age of the mother and smoking. BACKGROUND: Mean birthweight
      has been found to be increasing in many countries in recent years, but there are
      still a group of babies who are born with low birthweights. DESIGN: Population
      based retrospective cohort study. METHOD: Multiple linear regression and logistic
      regression models are used to analyse data on term 'singleton births' from
      Scottish hospitals between 1994-2003. RESULTS: Mothers who smoke are shown to
      give birth to lighter babies on average, a difference of approximately 0.57
      Standard deviations lower (95% confidence interval. 0.55-0.58) when adjusted for
      sex and parity. These mothers are also more likely to have babies that are low
      birthweight (odds ratio 3.46, 95% confidence interval 3.30-3.63) compared with
      non-smokers. Low birthweight is 30% more likely where the mother lives in the
      most deprived areas compared with the least deprived, (odds ratio 1.30, 95%
      confidence interval 1.21-1.40). CONCLUSIONS: Smoking during pregnancy is shown to
      have a detrimental effect on the size of infants at birth. This effect explains
      some, though not all, of the observed socioeconomic birthweight. It also explains
      much of the observed birthweight differences by the age of the mother. RELEVANCE
      TO CLINICAL PRACTICE:   Identifying mothers at greater risk of having a low
      birthweight baby as important implications for the care and advice this group
      receives.

PMID- 22882690
TI  - Pulmonary hamartoma masquerading lung metastasis in a woman with inflammatory
      breast cancer.

PMID- 22882691
TI  - Molecular identification of bloodmeals and species composition in Culicoides
      biting midges.
AB  - Investigations of host preferences in haematophagous insects, including
      Culicoides biting midges (Diptera: Ceratopogonidae), are critical in order to
      assess transmission routes of vector-borne diseases. In this study, we collected
      and morphologically identified 164 blood-engorged Culicoides females caught in
      both light traps and permanent 12-m high suction traps during 2008-2010 in
      Sweden. Molecular analysis of the mitochondrial cytochrome c oxidase subunit I
      (COI) gene in the biting midges was performed to verify species classification,
      discern phylogenetic relationships and uncover possible cryptic species.
      Bloodmeal analysis using universal vertebrate cytochrome b primers revealed a
      clear distinction in host selection between mammalophilic and ornithophilic
      Culicoides species. Host sequences found matches in horse (n = 59), sheep (n =
      39), cattle (n = 26), Eurasian elk (n = 1) and 10 different bird species (n =
      18). We identified 15 Culicoides species previously recorded in Scandinavia and
      four additional species haplotypes that were distinctly different from the
      described species. All ornithophilic individuals (n = 23) were caught exclusively
      in the suction traps, as were, interestingly, almost all mammalophilic species (n
      = 41), indicating that many biting midge species may be able to cover long
      distances after completing a bloodmeal. These results add new information on the
      composition of Culicoides species and their host preferences and their potential
      long-distance dispersal while blood-engorged.

PMID- 22882692
TI  - Antibody response to the non-adjuvanted and adjuvanted influenza A H1N1/09
      monovalent vaccines in renal transplant recipients.
AB  - BACKGROUND: The 2009 pandemic influenza A (H1N1) virus spread rapidly throughout
      Brazil. Non-adjuvanted and the adjuvanted influenza A H1N1/09 monovalent vaccine
      were recommended as a single dose to persons at risk including renal transplant
      recipients (RTR). We analyzed the safety and the immune response of 2 influenza A
      H1N1/09 monovalent vaccines in RTR, and identified factors influencing the immune
      response. METHODS: A total of 78 RTR received a single dose of either influenza A
      H1N1 2009 monovalent AS03-adjuvanted vaccine or a non-adjuvanted vaccine, and 58
      healthy controls received a single dose of non-adjuvanted vaccine. Antibody
      responses to influenza A H1N1 were measured by hemagglutination inhibition assay
      and were compared between groups on the day of vaccination and 21-30 days
      thereafter, using geometric mean titer (GMT), and seroprotection (SP) and
      seroconversion (SC) rates. RESULTS: Among RTR, after adjuvanted and non
      adjuvanted H1N1 vaccination, the SP rate increased from 16.7% to 61.7% (P <
      0.001) and to 50% (P < 0.001), and SC rates were 61.7% and 50%, respectively. For
      healthy controls, SP rate increased from 25.8% to 89.7% (P < 0.001), and SC rate
      was 87.9% after vaccination. Pre-vaccination GMT for the adjuvanted and non
      adjuvanted RTR vaccine groups and healthy controls was 9.7 (95% confidence
      interval [CI] 7.3-13.1), 8.9 (95% CI 5.4-14.7), and 12.5 (95% CI8.7-18.2), and
      significantly increased to 49.8 (95% CI 31.3-79.4, P < 0.001), 43.2 (95% CI 16.3
      114.4, P < 0.001), and 323.8 (95% CI 213.9-490.2, P < 0.001), respectively.
      Deceased-donor type transplant significantly reduced SP (odds ratio [OR] = 4.62,
      95% CI 1.36-15.69, P = 0.014) and SC (OR = 6.29, 95% CI 1.89-20.98, P = 0.003)
      rates, and younger age positively affected SP (OR = 0.11; 95% CI 0.03-0.04, P =
      0.001). Adverse events were mild, and renal function showed no change post
      vaccination. CONCLUSION: RTR vaccinated with either an adjuvanted or non
      adjuvanted monovalent influenza vaccine presented poor response compared with
      healthy controls. Post-vaccination adverse events were mild, and no rejection
      episode or renal dysfunction was observed.

PMID- 22882693
TI  - Multidrug-resistant Klebsiella pneumoniae acquisition in lung transplant
      recipients.
AB  - BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a pathogen that
      emerged in the late twentieth century and was associated with significant
      morbidity and mortality. We report for the first time the outcomes of lung
      transplant recipients infected with CRKP or extended spectrum-beta lactamases K.
      pneumoniae (ESBL-KP). METHODS: Retrospective review of 136 lung transplant
      recipients who underwent transplantation between 2004 and 2007 in Rabin Medical
      Center, Israel. MAIN RESULTS: There were 52 episodes of positive cultures for K.
      pneumoniae (KP) in 136 recipients - of them 11 (8.1%) with CRKP, 12 (8.8%) with
      ESBL-KP, and 29 (21.3%) with carbapenem-sensitive ESBL-negative KP. Isolation of
      CRKP/ESBL-KP was associated with death in the cohort (p < 0.0001) as well as
      recipients' age at transplantation (p < 0.005). Time-dependent age-adjusted CRKP
      or ESBL-KP acquisition was an independent factor for death in patients after lung
      transplant, compared to patients without KP isolation or carbapenem-sensitive
      ESBL-negative KP (p < 0.0001). CONCLUSION: CRKP and KP-ESBL acquisition was
      associated with reduced survival among lung transplant recipients.

PMID- 22882694
TI  - MELD scores with incorporation of serum sodium and death prediction in cirrhotic
      patients on the waiting list for liver transplantation: a single center
      experience in southern Brazil.
AB  - To compare the accuracy of standard model for end-stage liver disease (MELD)
      score with that of four MELD-based scores incorporating serum sodium (SNa) to
      predict three- and six-month mortality in cirrhotic patients after their
      placement on the waiting list for liver transplantation (LT). A cohort study was
      performed. Receiver operating characteristic (ROC) curves were generated for
      MELD, MELD incorporating SNa (MELD-Na, MELD-Na2), integrated MELD (iMELD), and
      MELD to SNa ratio (MESO) index to assess the predictive accuracy of these scores
      to determine three- and six-month mortality. The c-statistic (area under the ROC
      curve [AUC]) was used to determine predictive power and the Cox proportional
      hazard ratio to estimate death risk. We studied 558 patients. There was a
      statistically significant difference in the predictive accuracy of scores at
      three months (AUCs: MELD = 0.79 [95% CI = 0.72-0.87]; MELD-Na = 0.84 [95% CI =
      0.78-0.90]; MELD-Na2 = 0.85 [95% CI = 0.80-0.91]; iMELD = 0.85 [95% CI = 0.80
      0.90]; MESO = 0.81 [95% CI = 0.80-0.91]) and at six months (MELD = 0.73 [95% CI =
      0.67-0.80]; MELD-Na = 0.79 [95% CI = 0.73-0.84]; MELD-Na2 = 0.80 [95% CI = 0.74
      0.85]; iMELD = 0.80 [95% CI = 0.75-0.85]; MESO = 0.75 [95% CI = 0.69-0.81]) (p <
      0.001). Death risk was independent of age and sex. Sodium-modified MELD scores
      are able to more accurately predict three- and six-month mortality among
      cirrhotic patients awaiting LT.

PMID- 22882695
TI  - The pathogenesis of acute allograft dysfunction in desensitized renal transplant
      recipients.
AB  - BACKGROUND: Acute allograft rejection after HLA desensitization is common early
      post-transplant but the sequence of histopathologic changes leading to graft
      dysfunction has not been well defined. METHODS: We evaluated the early
      pathogenesis and sequence of antibody-mediated graft damage of 35 desensitized
      living donor kidney recipients by studying the course of biopsies taken in the
      very early post-transplant period (<1 month). RESULTS: A total of 14 of the 35
      patients met criteria for acute antibody-mediated rejection (AMR). In these
      patients, the chronologic sequence of pathologic changes was C4d peritubular
      capillary deposition, acute tubular injury, and peritubular capillaritis,
      followed by glomerulitis and interstitial inflammation. Classic AMR lesions
      occurred early, followed by mononuclear cellular infiltration, which comprised
      CD4 and CD8 T cells and monocytes. Development of graft dysfunction in most
      patients occurred concurrently with the emergence of graft cellular infiltration,
      rather than at the earlier time of antibody deposition as detected via C4d
      deposition. CONCLUSION: These data provide novel insight into the sequence of
      pathologic changes in patients with AMR post-transplant after HLA
      desensitization.

PMID- 22882696
TI  - Non-invasive imaging of living kidney donors: intraindividual comparison of
      multislice computed tomography angiography with magnetic resonance angiography.
AB  - BACKGROUND: Evaluation of vascular variants is crucial for donor assessment prior
      to living kidney transplantation. Both contrast-enhanced (CE) magnetic resonance
      angiography (MRA) and multislice computed tomography (MSCT) are currently used
      for imaging living kidney donors. Aim of this study was the comparison of the
      accuracy of MSCT angiography and CE-MRA for the assessment of renal vascular
      anatomy. METHODS: Prospective study at a university transplant center including
      65 potential living kidney donors. Pre-operative imaging by MSCT angiography and
      CE-MRA was correlated with the findings of laparoscopic donor nephrectomy in 48
      donors. RESULTS: MSCT detected significantly more patients and more kidneys with
      accessory arteries than CE-MRA (p < 0.05). MSCT and CE-MRA performed similarly in
      identifying venous and ureteral abnormalities. The overall sensitivity,
      specificity, and accuracy for identifying accessory arteries were 85%/97%/94% for
      MSCT and 54%/97%/85% for CE-MRA. The sensitivity, specificity, and accuracy for
      the identification of supernumerary veins were 67%/95%/92% for MSCT and
      67%/98%/94% for CE-MRA, respectively. CONCLUSION: We found MSCT angiography to be
      more sensitive and accurate than CE-MRA in the detection of supernumerary
      arteries prior to living donor nephrectomy.

PMID- 22882697
TI  - A prospective study on living related kidney donors' quality of life in the first
      year: choosing appropriate reference data.
AB  - Prospective studies on living kidney donors' quality of life (QoL) are still
      rare. Most existing studies compare healthy donors with the general population,
      including subjects with diseases. This is the first prospective study comparing
      living donors' QoL with reference data of both the general population and healthy
      individuals. We investigated QoL, anxiety, and depression in living kidney donors
      (n = 79) before donation and at two post-operative data points (three months and
      one yr). Subsequently, data from the donors were compared with the reference
      data. Our results show an impaired physical QoL three months post-donation. One
      yr after surgery, physical QoL had returned to the pre-operative level. Neither
      mental QoL nor anxiety or depression showed major changes across time. Pre
      operative QoL was comparable to that of healthy individuals and higher than that
      in the general population. Donors' perception of the recipient's health showed
      moderate correlations with donors' mental outcome three months after donation. In
      conclusion, the impact on physical QoL seems to persist for at least three months
      after kidney donation. It could be demonstrated that in the context of living
      donation, healthy individuals provide more adequate reference data. Future
      research needs to determine the length and the nature of the post-operative QoL
      impairment and further explore possible influencing factors.

PMID- 22882698
TI  - Pemetrexed plus platinum or gemcitabine plus platinum for advanced non-small cell
      lung cancer: final survival analysis from a multicentre randomized phase II trial
      in the East Asia region and a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Pemetrexed plus platinum has shown efficacy as a first
      line treatment for advanced non-small cell lung cancer (NSCLC), but little is
      known about its efficacy and safety in East Asian patients. We report the final
      analysis of overall survival (OS) from a multicentre, randomized, phase II trial
      in chemotherapy-naive Chinese patients with advanced NSCLC. An additional meta
      analysis was performed to systematically evaluate pemetrexed/platinum as first
      line treatment for advanced NSCLC. METHODS: Eligible patients received up to six
      cycles of pemetrexed, 500 mg/m(2) plus cisplatin, 75 mg/m(2) (day 1) or
      gemcitabine, 1000 mg/m(2) (days 1 and 8) plus cisplatin, 75 mg/m(2) (day 1). OS
      and toxicity were assessed. RESULTS: A total of 254 patients were randomized, and
      251 were eligible for inclusion in the efficacy and safety analyses. Median OS in
      the pemetrexed/cisplatin arm was 15.3 months, compared with 16.9 months in the
      gemcitabine/cisplatin arm [hazard ratio (HR) 1.09; 95% confidence interval (CI)
      0.80-1.48; log-rank P = 0.4888). There was a trend towards improved survival in
      both arms. Patients in the pemetrexed/cisplatin arm showed a lower incidence of
      drug-related grade 3 to 4 leukopenia and thrombocytopenia. Meta-analysis showed
      that pemetrexed-platinum treatment was associated with 19% longer survival among
      females (HR 0.81; 95% CI 0.69-0.96) and 17% longer survival among patients with
      non-squamous cell lung cancer (HR 0.83; 95% CI 0.73-0.95). CONCLUSIONS: In
      Chinese patients with advanced NSCLC, pemetrexed/cisplatin treatment resulted in
      comparable OS outcomes and was better tolerated than gemcitabine/cisplatin. Meta
      analysis supports the use of pemetrexed-platinum as first-line treatment for
      female patients and those with the non-squamous cell subtype of advanced NSCLC.

PMID- 22882699
TI  - Novel histologic scoring system for long-term allograft fibrosis after liver
      transplantation in children.
AB  - The existing systems for scoring fibrosis were not developed to evaluate
      transplanted livers. Our aim was to design and validate a novel fibrosis scoring
      system specifically adapted to assess liver allograft fibrosis (LAF). Clinical
      data, histology, transient elastography (TE) and AST/platelet ratio index (APRI)
      were reviewed in 38 pediatric liver transplant (LT) recipients. Protocol liver
      biopsies performed at 6 months and 7 years post-LT were reviewed by three
      pathologists who assessed LAF using the METAVIR and Ishak systems. LAF was also
      scored separately in portal (0-3), sinusoidal (0-3) and centrolobular areas (0
      3). Scoring evaluations were correlated with fibrosis quantification using
      morphometry, and also with TE and APRI. Statistical correlations between
      morphometry and METAVIR were 0.571 (p < 0.000) and 0.566 (p < 0.000) for the
      Ishak system. The novel score (0-9) for separate assessment of portal, sinusoidal
      and centrolobular fibrosis showed a better correlation with morphometry (0.731; p
      < 0.000) and high intra-/interobserver agreement (0.966; p < 0.000 and 0.794; p <
      0.000, respectively). No correlation was found between TE or APRI and morphometry
      or the three histologic scores. In conclusion, this novel semiquantitative
      fibrosis scoring system seems to more accurately reflect LAF than the existing
      scoring system and may become a practical tool for staging fibrosis in LT.

PMID- 22882700
TI  - Does residual cement around implant-supported restorations cause peri-implant
      disease? A retrospective case analysis.
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      patients with a history of periodontitis and development of cement-related peri
      implant disease. MATERIALS AND METHODS: Seventy-seven patients with 129 implants
      for this retrospective analysis were selected from completed implant cases that
      were scheduled for regular maintenance or had experienced mechanical or
      biological complications between years 2006 and 2011 in private practice.
      Implants with extracoronal residual cement and implants without cement remnants
      were analyzed. The selected cases were further divided into two groups--implants
      in patients with history of periodontitis (1) and implants in periodontitis-free
      individuals (2). The selection of these groups was made on the basis of treatment
      history and orthopantomograph. As a control group, a set of 238 screw-retained
      implant restorations, delivered to 66 patients during the same period of time was
      examined. The incidence of peri-implant disease among implants in all groups was
      calculated. RESULTS: Peri-implant disease was evident in 62 of 73 implants with
      cement remnants (85%). All implants in group 1 developed peri-implantitis--4
      early and 35 delayed disease cases. In the periodontally healthy group, 20 of 31
      implants were diagnosed with peri-implant mucositis, 3 implants had early peri
      implantitis, and 11 implants with cement remnants did not develop biological
      complications. In the group of implants without cement remnants, peri-implant
      disease was diagnosed in 17 of 56 cases (30%). In contrast, only two occurrences
      of peri-implant disease were registered in the control group of screw-retained
      restorations (1.08%). CONCLUSIONS: Implants with cement remnants in patients with
      history of periodontitis may be more likely to develop peri-implantitis, compared
      with patients without history of periodontal infection.

PMID- 22882701
TI  - Safety and effectiveness of transvenous lead extraction in octogenarians.
AB  - INTRODUCTION: As the population ages, the number of elderly patients with
      implantable cardiac devices referred for transvenous lead extraction will
      dramatically increase in Western countries. The safety and effectiveness of lead
      extraction in elderly patients has not been well evaluated. We report the safety
      and effectiveness of transvenous lead extraction in octogenarians. METHODS AND
      RESULTS: From January 2005 to January 2011, we reviewed data from consecutive
      patients >= 80 years referred to our institutions for transvenous lead extraction
      because of cardiac device infection or lead malfunction. Clinical
      characteristics, procedural features, and periprocedural major and minor
      complications were compared between octogenarians and younger patients. Out of
      849 patients undergoing lead extraction in the participating institutions during
      the study period, 150 (18%) patients were octogenarians (mean age 84 years; range
      80-96; 64% males). A significantly higher percentage of octogenarians presented
      with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs
      6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P <
      0.001). Complete lead extraction rates were similar in the 2 age groups (97% in
      octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death
      occurred in 2 (1.3%) patients >=80 years and in 5 (0.72%) patients <80 years (P =
      0.45 for comparison). No differences in terms of other periprocedural major and
      minor complications were found between the 2 age groups. CONCLUSION: Despite
      presenting with a significantly higher rate of comorbidities, transvenous lead
      extraction can be performed safely and successfully in octogenarians.

PMID- 22882702
TI  - The structure of acute stress disorder among Chinese adults exposed to an
      earthquake: is dysphoric arousal a unique construct of acute posttraumatic
      responses?
AB  - As a diagnosis organized mainly on the basis of theoretical conceptualization,
      acute stress disorder (ASD) has been widely criticized for lack of empirical
      support since it was introduced into the DSM system. To address this issue, the
      present study investigated the latent structure of ASD symptoms measured by the
      Acute Stress Disorder Scale (ASDS). A total of 350 adults with a mean age of 32.9
      years (SD = 14.0, range: 16-85) took part in this study 12 to 15 days after an
      earthquake. The results of confirmatory factor analyses showed that a five-factor
      intercorrelated model (dissociation, reexperiencing, avoidance, dysphoric
      arousal, and anxious arousal) demonstrated the best data fit. The findings
      provide preliminary empirical evidence in favor of a new reconceptualization of
      ASD symptoms, and are informative for the impending DSM-5.

PMID- 22882703
TI  - Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non
      small-cell lung cancer biopsies.
AB  - AIMS: Patient stratification according to histological subtype is important for
      non-small-cell lung cancer (NSCLC) therapy. For specimens with uncertain
      histomorphology, rational and material-saving algorithms for specific and
      sensitive immunotyping need to be established. METHODS AND RESULTS: One thousand
      one hundred and forty-five NSCLCs were immunohistochemically investigated for the
      expression of cytokeratin 5/6 (CK5/6), CK7, thyroid transcription factor-1 (TTF
      1), p63, napsin-A, and desmocollin-3. Overall, napsin-A and desmocollin-3 were
      the most specific markers (specificity of each, 99%), and CK7 and CK5/6 the most
      sensitive markers (sensitivity, 96% and 94%) for adenocarcinomatous and squamous
      differentiation, respectively. However, for NSCLC not otherwise specified (NOS)
      cases, TTF-1, p63, CK5/6 and CK7 were found to be the most reliable markers. On
      the basis of morphology alone, approximately two-thirds of all NSCLCs could be
      reliably diagnosed in biopsy specimens. Immunohistochemistry further reduced the
      NOS fraction to 10%. CONCLUSIONS: When morphology alone is not reliable, the use
      of selected markers and marker panels is highly sensitive and specific, and
      allows reliable distinction between squamous cell carcinoma and adenocarcinoma.
      Considering the impact of typing for the selection of molecular testing and
      treatment response, one must be aware of immunomarker expression patterns in
      NSCLC and their diagnostic value, in order to optimize typing and thereby
      maximize patient benefit from chemotherapy.

PMID- 22882704
TI  - Constructing denial as a disease object: accounts by medical students meeting
      dying patients.
AB  - As part of the general shift in contemporary healthcare from a focus on specific
      diseases to treating the whole person, doctors are now expected to be reflective
      and engage empathetically with patients. Yet, the context of end of life
      potentially confounds this commitment. Here we draw on the written submissions of
      UK medical students confronting dying patients to offer insight into a range of
      entangled issues. Although the exercise is designed to highlight the value of
      listening to patients and to encourage reflective practice, the experience of
      ultimately not being able to treat or cure frequently challenges the students'
      understanding of the central purpose of clinical care and their future role as
      doctors. Because they invariably draw on the notion of 'good death', whenever
      they have to make sense of patient behaviour deemed as irrational or obstructive
      the students employ the concept of 'denial' as a strategic category. In this
      context denial is referred to as a disease-like object that the students feel
      they can, and should, diagnose and treat. Such conceptual operations consequently
      illustrate a tension arising from trying to acknowledge the value of a whole
      patient approach while simultaneously reproducing the emphasis placed on
      identifying those discrete elements that determine legitimate medical
      intervention. 

PMID- 22882705
TI  - Obstructive sleep apnea in incremental hemodialysis: determinants, consequences,
      and impact on survival.
AB  - Sleep disorders are common in hemodialysis patients, although causes and
      consequences remain unclear. We sought to establish prevalence, determinants, and
      outcomes of sleep disturbances in patients receiving incremental dialysis. One
      hundred two unselected patients undergoing incremental high-flux hemodialysis or
      hemodiafiltration underwent limited overnight sleep study. Large subsets
      underwent echocardiography, interdialytic ambulatory blood pressure monitoring,
      and brain natriuretic peptide measurements. Patients were followed up to 44
      months. Full sleep data were obtained in 91 patients. All had sleep disturbance
      as evidenced by an apnea-hypopnea index >5/min. We defined major obstructive
      sleep apnea (MOSA) as an apnea-hypopnea index >= 15, together with either
      significant oxygen desaturation or symptoms of daytime sleepiness. Forty patients
      met these criteria. Significant independent predictors of MOSA were age <65
      years, male gender, has diabetes, and has a brain natriuretic peptide >2500
      pg/mL. Mean ambulatory blood pressure and left ventricular mass index were
      significantly higher in these patients. In a model controlling for body mass
      index, high C-reactive protein, and the presence of cancer, MOSA was associated
      with a twofold increased risk of mortality, although this did not reach
      statistical significance. MOSA was common, and was associated with hypertension
      and high left ventricular mass index. Whether obstructive sleep apnea contributes
      to the high mortality remains to be firmly established.

PMID- 22882706
TI  - Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major
      orthopedic surgery: findings from the ORTHO-TEP registry.
AB  - BACKGROUND: Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in
      patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has
      never been directly compared with fondaparinux (F), which also shows superior
      efficacy over enoxaparin. The clinical impact of switching from fondaparinux to
      rivaroxaban thromboprophylaxis is unclear. OBJECTIVES: To evaluate the efficacy
      and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected
      patients undergoing MOS. PATIENTS/METHODS: This is a monocentric, retrospective
      cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing
      rates of symptomatic VTE, bleeding and surgical complications, length of hospital
      stay and risk factors for VTE. RESULTS: Rates of symptomatic VTE were 5.6% (F)
      and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P <
      0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs.
      1.1%), but not statistically significant. Rates of severe bleeding (bleeding
      leading to surgical revision or death, occurring in a critical site, or
      transfusion of at least two units of packed red blood cells) were statistically
      lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The
      mean length of hospital stay was significantly shorter in the rivaroxaban group
      (8.3 days, 95% CI 8.1-8.5 vs. 9.3 days, 9.1-9.5; P < 0.001). CONCLUSION: Based on
      an indirect comparison of two consecutive cohorts, our data suggest that
      thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding
      events than fondaparinux in unselected patients undergoing MOS. Prospective
      comparisons are warranted to confirm our findings.

PMID- 22882707
TI  - Acute cocaine intoxication and questionnaires.

PMID- 22882708
TI  - Spine surgery outcomes in a workers' compensation cohort.
AB  - INTRODUCTION: Lumbar spine surgery (fusion, disc replacement or decompression) is
      common, yet indications are unclear and outcomes, particularly in a workers'
      compensation setting, are not consistently favourable. This study aimed to
      determine the outcomes of spine surgery in an Australian workers' compensation
      cohort. METHODS: A retrospective review of prospectively collected data from
      WorkCover NSW and insurer agents was performed. Subjects were included if they
      had lumbar spine decompression, fusion or disc replacement procedures performed
      between 1 January 2004 and 31 December 2006 (inclusive). Main outcome measures
      were as follows: need for further lumbar spine surgery, return to work (RTW),
      return to pre-injury duties (PID) and need for ongoing physical treatment or
      prescription opioids. All outcomes were measured at 24 months post-surgery.
      RESULTS: A total of 476 patients had undergone lumbar spine surgery within the
      workers' compensation system. The revision surgery rate was 9.2%. The RTW rate
      and return to PID rate were 50.3% and 14.2%, respectively. The proportion of
      patients still undergoing treatment was 77.7%. The rates of RTW (or PID) and need
      for ongoing treatment were significantly worse in patients undergoing fusion and
      disc replacement, compared with patients undergoing decompressive procedures
      (laminectomy, discectomy). DISCUSSION: The findings do not support the use of
      lumbar spine fusion or disc replacement surgery as a method of achieving RTW and
      relief of pain in patients treated under workers' compensation.

PMID- 22882709
TI  - Developing vaccines in the era of genomics: a decade of reverse vaccinology.
AB  - Vaccines have a significant impact on public health, and vaccinology in the era
      of genomics is taking advantage of new technologies to tackle diseases for which
      vaccine development has so far been unsuccessful. Almost all existing vaccines
      were developed based on traditional vaccinology methods, which relied on
      empirical screening of a few candidates at a time, based on known features of the
      pathogen. However, the ability to sequence a pathogen's genome provides access to
      its entire antigenic repertoire. As such, genomics has catalysed a shift in
      vaccine development towards sequence-based 'Reverse Vaccinology' approaches,
      which use high-throughput in silico screening of the entire genome of a pathogen
      to identify genes that encode proteins with the attributes of good vaccine
      targets. Furthermore, the increasing availability of genome sequences has led to
      the development and application of additional technologies to vaccine discovery,
      including comparative genomics, transcriptomics, proteomics, immunomics and
      structural genomics. Vaccine candidates identified from a pathogen's genome or
      proteome can then be expressed as recombinant proteins and tested in appropriate
      in vitro or in vivo models to assess immunogenicity and protection. The process
      of reverse vaccinology has been applied to several pathogens, including serogroup
      B Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pyogenes,
      Streptococcus pneumoniae and pathogenic Escherichia coli, and has provided scores
      of new candidate antigens for preclinical and clinical investigation. As novel
      genome-based technologies continue to emerge, it is expected that new vaccines
      for unmet diseases will be within reach.

PMID- 22882710
TI  - Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum
      bv. infantis CCUG 52486.
AB  - Bifidobacterium longum bv. infantis CCUG 52486 was originally isolated from
      healthy elderly subjects and demonstrated to have particular ecological fitness
      and anti-pathogenic effects. Bifidobacteria are commonly associated with immuno
      modulatory properties, especially in older people, but this strain has not been
      investigated for effects on immune function. This study aimed to explore the
      immunomodulatory effects of this novel probiotic, compared with three commercial
      strains, B. longum SP 07/3, Lactobacillus rhamnosus GG (L.GG) and Lactobacillus
      casei Shirota (LcS). Human peripheral blood mononuclear cells (PBMCs) were
      isolated from fasting blood of young or older volunteers and exposed to probiotic
      strains or Con A. NK activity and activation, and cytokine release was enhanced
      by all probiotics with strain specificities. The effect of B. infantis on NK
      activity was influenced by ageing. Except for L.GG, probiotics increased IFN
      gamma production to a much greater degree in young subjects and increased IL-6
      production to a much greater degree in older subjects. Based on IL-10/IL-12
      ratios, B. infantis resulted in the most anti-inflammatory profile of all of the
      probiotics. These results suggest that B. infantis CCUG 52486 has strong
      immunomodulatory potential compared with well-known commercial strains and that
      the immune response to probiotics may be influenced by ageing.

PMID- 22882711
TI  - Cerebrolysin administration reduces oxidative stress-induced apoptosis in
      lymphocytes from healthy individuals.
AB  - Cerebrolysin is the only drug available for clinical use containing active
      fragments of some important neurotrophic factors obtained from purified porcine
      brain proteins, which has long been used for the treatment of dementia and stroke
      sequels. Cerebrolysin has growth factor-like activities and promotes neuronal
      survival and sprouting, however, its molecular mechanism still needs to be
      determined. It has been shown that Cerebrolysin may interact with proteolytic
      pathways linked to apoptosis. Administration of Cerebrolysin significantly
      reduces the number of apoptotic neurons after glutamate exposure. Furthermore, it
      has been reported that Cerebrolysin inhibits free radicals formation and lipid
      peroxidation. In vitro we evaluated the protective effects of Cerebrolysin
      towards spontaneous and induced apoptotic death in cells from healthy
      individuals. Peripheral blood lymphocytes (PBLs) from 10 individuals were used as
      cell model; 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as
      paradigm pro-apoptotic stimulus. Apoptosis was analysed using flow cytometry and
      fluorescence microscopy. Our results showed that Cerebrolysin significantly
      reduced the number of apoptotic PBLs after dRib treatment, although it had no
      significative effects on cells cultured in standard conditions. Our work showed a
      protective effect of Cerebrolysin on oxidative stress-induced apoptosis and
      suggested that PBLs can be used as an easy obtainable and handy cell model to
      verify Cerebrolysin effects in neurodegenerative pathologies.

PMID- 22882712
TI  - A cross-sectional study: non-carious cervical lesions, cervical dentine
      hypersensitivity and related risk factors.
AB  - The present survey aims to study the prevalence and clinical characteristics of
      non-carious cervical lesions (NCCLs) and cervical dentine hypersensitivity (CDH),
      as well as their possible risk factors in a general population in China. A total
      of 1023 subjects were included in the present study. Each subject completed a
      structured interview, and all teeth of each subject were examined by a
      practitioner to determine NCCLs and CDH. Teeth with NCCLs and CDH were diagnosed
      according to the tooth wear index and by a blast of air from a triple syringe,
      respectively. Binary logistic regression was completed by analysing the
      association of risk factors with the occurrence of NCCLs and CDH. Loss of
      attachment (LOA) and gingival recession (GR) of teeth with NCCLs and/or CDH were
      measured using Williams periodontal probe. The diagnoses of NCCLs and CDH
      established following a clinical assessment yielded an overall prevalence of
      61.7% and 27.1%, respectively. The 60-69 age group had the greatest proportion of
      subjects with NCCLs or CDH. The pre-molars were the most commonly affected teeth
      type with NCCLs or CDH. The proportion of teeth with CDH associated with NCCLs
      increased significantly with age, but the proportion of teeth with CDH only
      associated with LOA or GR decreased slowly with age. The single variables and
      interactive effects of variables associated with the occurrence of NCCLs include
      the following: age group, occupation type, method of toothbrushing, frequency and
      method of toothbrushing, and method of toothbrushing and duration of a toothbrush
      used. Gender, age group, occupation type and frequency of toothbrushing were
      associated with the occurrence of CDH. The current study presented higher
      prevalence of NCCLs and CDH in a general Chinese population. Both diseases were
      closely associated with age and periodontal status. The portion of the population
      with NCCLs or CDH had different risk factors.

PMID- 22882713
TI  - Clinical and neuropathological findings in a patient with familial Alzheimer
      disease showing a mutation in the PSEN1 gene.
AB  - Over 100 mutations have been described in the presenilin-1 gene (PSEN1),
      resulting in familial Alzheimer disease (AD). However, of the limited number of
      autopsy cases, only one has been reported from an AD family with an L420R PSEN1
      mutation. We describe here clinical and neuropathological features of a patient
      with dementia-parkinsonism from a family with a PSEN1 mutation (L420R). A 43-year
      old Japanese woman was autopsied 12 years after the onset of her progressive
      dementia and 4 years after the onset of parkinsonism. Throughout the neocortex
      and hippocampus, cotton wool plaques were identified, densely packed, in almost
      all the cortical layers along with neuronal loss, gliosis, NFT and neuropil
      threads. In addition, CAA affecting meningeal, subpial and cortical arterioles
      was found, as well as amyloid beta-protein (Abeta)-deposition in the capillaries
      (capillary CAA) in the neocortex and subcortical nuclei. There was loss of
      pigmented neurons in the substantia nigra. The putamen was densely packed with
      diffuse plaques and rarely showed capillary CAA, whereas the globus pallidus
      showed extensive capillary CAA but no plaques. This differential distribution is
      similar to that reported for a previous patient with a mutation in PSEN1. It is
      concluded that neuropathological changes in the substantia nigra and lenticular
      nuclei were responsible for the patient's parkinsonism. Capillary transport of
      Abeta unique to the respective tissue of the patient may result in the
      differential distribution of Abeta between the putamen and globus pallidus seen
      in individuals with a PSEN1 mutation.

PMID- 22882714
TI  - Effect of obstetric team training on team performance and medical technical
      skills: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether obstetric team training in a medical simulation
      centre improves the team performance and utilisation of appropriate medical
      technical skills of healthcare professionals. DESIGN: Cluster randomised
      controlled trial. SETTING: The Netherlands. SAMPLE: The obstetric departments of
      24 Dutch hospitals. METHODS: The obstetric departments were randomly assigned to
      a 1-day session of multiprofessional team training in a medical simulation centre
      or to no such training. Team training was given with high-fidelity mannequins by
      an obstetrician and a communication expert. More than 6 months following
      training, two unannounced simulated scenarios were carried out in the delivery
      rooms of all 24 obstetric departments. The scenarios, comprising a case of
      shoulder dystocia and a case of amniotic fluid embolism, were videotaped. The
      team performance and utilisation of appropriate medical skills were evaluated by
      two independent experts. MAIN OUTCOME MEASURES: Team performance evaluated with
      the validated Clinical Teamwork Scale (CTS) and the employment of two specific
      obstetric procedures for the two clinical scenarios in the simulation (delivery
      of the baby with shoulder dystocia in the maternal all-fours position and
      conducting a perimortem caesarean section within 5 minutes for the scenario of
      amniotic fluid embolism). RESULTS: Seventy-four obstetric teams from 12 hospitals
      in the intervention group underwent teamwork training between November 2009 and
      July 2010. The teamwork performance in the training group was significantly
      better in comparison to the nontraining group (median CTS score: 7.5 versus 6.0,
      respectively; P = 0.014). The use of the predefined obstetric procedures for the
      two clinical scenarios was also significantly more frequent in the training group
      compared with the nontraining group (83 versus 46%, respectively; P = 0.009).
      CONCLUSIONS: Team performance and medical technical skills may be significantly
      improved after multiprofessional obstetric team training in a medical simulation
      centre.

PMID- 22882715
TI  - Baboon spermatology: basic assessment and reproducibility in olive baboons (Papio
      anubis).
AB  - BACKGROUND: Development of a reproducible baboon in vitro fertilization (IVF)
      system require optimized and reproducible sperm parameters. The objective of this
      study was to document basic spermatology values and investigate the
      reproducibility of these variables in the same baboons 1 or 3 months later in a
      larger number of baboons. METHODS: In this prospective study, sperm quality
      (semen volume, pH, concentration, motility, morphology and size) was evaluated in
      27 sperm samples obtained from 9 baboons electroejaculated three times with a
      time interval of 1 month (between first and second sample collection) and 3
      months (between second and third round sample collection). RESULTS: Baseline
      sperm values for semen volume (0.5 +/- 0.3 ml), pH (7.5 +/- 0.3), concentration
      (54.2 +/- 19.3 million/ml), motility (67.3 +/- 18.5%) and morphology (89.2 +/-
      4.8%) were similar to sperm samples obtained after 1 or 3 months (P > 0.05).
      Head, midpiece and tail abnormalities were rarely observed (0-9%). Sperm
      dimensions were characterized by a tail length of 69.6 +/- 13.9 MUm, a head width
      of 2.41 +/- 0.43 MUm and a head length of 3.49 +/- 0.6 MUm. CONCLUSION: Sperm
      quality was not affected by repeated electroejaculation with time intervals of 1
      or 3 months, suggesting that the same baboon can participate multiple times in
      reproductive research.

PMID- 22882716
TI  - Association between the insulin-like growth factor axis in serum and
      periodontitis in the Study of Health in Pomerania: an exploratory study.
AB  - AIM: To evaluate the association of Insulin-like Growth Factor (IGF) I-related
      variables with periodontitis in the population-based Study of Health in Pomerania
      (SHIP). MATERIAL AND METHODS: From the cross-sectional SHIP, 2293 subjects with
      clinical attachment loss (CAL) data and 2398 subjects with tooth count data aged
      20-59 years were analysed. Serum IGF-I and IGF-binding protein (BP)-3 levels were
      determined by chemiluminescence immunoassays. Linear and logistic regressions
      with fractional polynomials were used to study associations between IGF-related
      variables and mean CAL or high tooth loss. For non-linear relations between IGFBP
      3 and mean CAL, graphical presentations of fractional polynomials were used to
      deduce knots for linear splines. RESULTS: In fully adjusted models, for serum
      IGFBP-3 values <=1200 ng/ml, mean CAL increased significantly for decreasing
      serum IGFBP-3 levels [B = -0.027 (95% CI, -0.049; -0.005), p = 0.02]. The odds
      for high tooth loss decreased significantly for high serum IGFBP-3 values [OR =
      0.97 (0.95; 0.99), p = 0.02]. Serum IGF-I levels and the IGF-I/IGFBP-3 ratio were
      not related to mean CAL or tooth loss after full adjustment. CONCLUSIONS: Low
      serum IGFBP-3 levels might be associated with higher levels of periodontal
      disease. Neither serum IGF-I nor IGF-I/IGFBP-3 ratios were associated with
      periodontitis.

PMID- 22882717
TI  - The evolving conception and management challenges of malignant fibrous
      histiocytoma.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) is a rare and aggressive tumor.
      Mohs micrographic surgery (MMS) has been reported as an effective treatment,
      although most cases were published before advances in cytopathologic techniques
      led to reclassification of many tumors. OBJECTIVE: To evaluate a contemporary
      cohort of individuals with MFH and analyze management practices. METHODS: We
      reviewed all cases of MFH diagnosed at our institution from January 1995 to
      December 2010, evaluating 839 records to identify 36 patients undergoing
      management of tumors of the head and neck. RESULTS: Seventeen of the total 36
      patients (47%; mean age 67) experienced tumor recurrence, and 10 (28%) developed
      metastases. Seven of nine patients initially treated with MMS (78%), and 10 of 24
      (42%) treated with WLE experienced recurrence (p = .06). Patients treated with
      MMS had smaller tissue defects after surgery. The mean contemporary recurrence
      rate of MFH treated with MMS is significantly higher (58.8%) than the cumulative
      recurrence rate reported before 2000 (7.4%) (p < .001). CONCLUSIONS: Our study is
      consistent with reports of MFH as an aggressive neoplasm and describes the
      largest population treated with MMS in 3 decades. The changing conception of MFH,
      along with a propensity for in-transit metastases, may explain higher
      contemporary recurrence rates.

PMID- 22882718
TI  - The small regulatory RNA FasX controls pilus expression and adherence in the
      human bacterial pathogen group A Streptococcus.
AB  - Bacterial pathogens use cell surface-associated adhesion molecules to promote
      host attachment and colonization, and the ability to modulate adhesion expression
      is critical to pathogen success. Here, we show that the human-specific pathogen
      the group A Streptococcus (GAS) uses a small regulatory RNA (sRNA) to regulate
      the expression of adhesive pili. The fibronectin/fibrinogen-binding/haemolytic
      activity/streptokinase-regulator-X (FasX) sRNA, previously shown to positively
      regulate expression of the secreted virulence factor streptokinase (SKA),
      negatively regulates the production of pili on the GAS cell surface. FasX base
      pairs to the extreme 5' end of mRNA from the pilus biosynthesis operon, and this
      RNA:RNA interaction reduces the stability of the mRNA, while also inhibiting
      translation of at least the first gene in the pilus biosynthesis operon (cpa,
      which encodes a minor pilin protein). The negative regulation of pilus expression
      by FasX reduces the ability of GAS to adhere to human keratinocytes. Our findings
      cement FasX sRNA as an important regulator of virulence factor production in GAS
      and identify that FasX uses at least three distinct mechanisms, positive (ska
      mRNA) and negative (pilus operon mRNA) regulation of mRNA stability, and negative
      regulation of mRNA translation (cpa mRNA), to post-transcriptionally regulate
      target mRNAs during infection.

PMID- 22882719
TI  - Microstructural abnormalities of white matter differentiate pediatric and adult
      onset bipolar disorder.
AB  - OBJECTIVES: White-matter microstructure, known to undergo significant
      developmental transformation, is abnormal in bipolar disorder (BD). Available
      evidence suggests that white-matter deviation may be more pronounced in pediatric
      than adult-onset BD. The present study aimed to examine how white-matter
      microstructure deviates from a typical maturational trajectory in BD. METHODS:
      Fractional anisotropy (FA) was measured in 35 individuals presenting with first
      episode BD (type I) and 46 healthy controls (HC) (aged 9-42) using diffusion
      tensor imaging (DTI). Patients were medication free and close to illness onset at
      the time of the DTI scans. Tract-based spatial statistics were used to examine
      the center of white-matter tracts, and FA was extracted from nine tracts of
      interest. Axial, radial, and mean diffusivity were examined in post-hoc analyses.
      RESULTS: The left anterior limb of the internal capsule (ALIC) showed
      significantly lower FA in pediatric than adult-onset BD. The lower FA in BD was
      due primarily to greater radial, rather than decreased axial, diffusivity.
      CONCLUSIONS: The ALIC connects the frontal lobes with archistriatum, thalamus,
      and medial temporal regions, and alteration in these pathways may contribute to
      mood dysregulation in BD. Abnormalities in this pathway appear to be associated
      with an earlier onset of illness and thus may reflect a greater susceptibility to
      illness.

PMID- 22882720
TI  - Restless legs syndrome: impact on sleep-related breathing disorders.
AB  - Restless legs syndrome (RLS) is a common chronic sensory-motor neurological
      disorder that remains a clinical diagnosis. Most RLS patients present with sleep
      complaints in the form of initiation and/or maintenance insomnia as RLS has a
      circadian rhythmicity. An increased number of periodic leg movements during sleep
      (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the
      central dopaminergic and iron systems are involved in the physiopathology of RLS.
      There is a higher prevalence of RLS and PLMS in sleep-disordered breathing
      patients, particularly those with obstructive sleep apnoea (OSA), the most common
      sleep disorder in western societies. The complex mechanisms underlying the
      association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to
      adverse cardiovascular consequences due to cardio-metabolic dysfunction. It
      remains controversial whether RLS could further adversely impact the
      cardiovascular consequences of OSA. The PLMS do not have an additive effect on
      the hypersomnia experienced by some sleep-disordered breathing patients.
      Continuous positive airway pressure (CPAP) therapy is the most effective therapy
      for OSA. The presence of PLMS during CPAP treatment could be a marker of an
      incomplete resolution of sleep-disordered breathing in the form of increased
      upper airway resistance syndrome, despite treatment. Dopaminergic agonists are
      the preferred agent for the treatment of RLS, and are indicated when RLS symptoms
      are frequent and affect quality of life. PLMS and RLS do not seem to contribute
      to the residual hypersomnia that can be observed in some sleep-disordered
      breathing patients despite adequate compliance and effective CPAP therapy.

PMID- 22882722
TI  - Interventional electrophysiology at the crossroads: cardiac mapping, ablation and
      pacing without fluoroscopy.

PMID- 22882721
TI  - Development and preliminary validation of an indirect screener for drug use in
      the perinatal period.
AB  - AIMS: This study sought to develop and begin validation of an indirect screener
      for identification of drug use during pregnancy, without reliance on direct
      disclosure. DESIGN: Women were recruited from their hospital rooms after giving
      birth. Participation involved (i) completing a computerized assessment battery
      containing three types of items: direct (asking directly about drug use), semi
      indirect (asking only about drug use prior to pregnancy) and indirect (with no
      mention of drug use), and (ii) providing urine and hair samples. An optimal
      subset of indirect items was developed and cross-validated based on ability to
      predict urine/hair test results. SETTING: Obstetric unit of a university
      affiliated hospital in Detroit. PARTICIPANTS: Four hundred low-income, African
      American, post-partum women (300 in the developmental sample and 100 in the cross
      validation sample); all available women were recruited without consideration of
      substance abuse risk or other characteristics. MEASUREMENTS: Women first
      completed the series of direct and indirect items using a Tablet PC; they were
      then asked for separate consent to obtain urine and hair samples that were tested
      for evidence of illicit drug use. FINDINGS: In the cross-validation sample, the
      brief screener consisting of six indirect items predicted toxicology results more
      accurately than direct questions about drug use (area under the ROC curve = 0.74,
      P < 0.001). Traditional direct screening questions were highly specific, but
      identified only a small minority of women who used drugs during the last
      trimester of pregnancy. CONCLUSIONS: Indirect screening may increase the accuracy
      of mothers' self-reports of prenatal drug use.

PMID- 22882723
TI  - Income of living kidney donors and the income difference between living kidney
      donors and their recipients in the United States.
AB  - Disincentives for living kidney donation are common but are poorly understood. We
      studied 54 483 living donor kidney transplants in the United States between 2000
      and 2009, limiting to those with valid zip code data to allow determination of
      median household income by linkage to the 2000 U.S. Census. We then determined
      the income and income difference of donors and recipients. The median household
      income in donors and recipients was $46 334 +/-$17 350 and $46 439 +/-$17 743,
      respectively. Donation-related expenses consume >= 1 month's income in 76% of
      donors. The mean +/- standard deviation income difference between recipients and
      donors in transplants involving a wealthier recipient was $22 760 +/- 14 792 and
      in 90% of transplants the difference was <$40 000 dollars. The findings suggest
      that the capacity for donors to absorb the financial consequences of donation, or
      of recipients to reimburse allowable expenses, is limited. There were few
      transplants with a large difference in recipient and donor income, suggesting
      that the scope and value of any payment between donors and recipients is likely
      to be small. We conclude that most donors and recipients have similar modest
      incomes, suggesting that the costs of donation are a significant burden in the
      majority of living donor transplants.

PMID- 22882724
TI  - Prucalopride in the treatment of chronic constipation in patients from the Asia
      Pacific region: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: The study evaluated efficacy and safety of the 2 mg dose of
      prucalopride compared to placebo in patients with chronic constipation (CC) from
      the Asia-Pacific region. METHODS: Randomized, placebo-controlled, parallel-group,
      phase III study with 2-week run-in, 12-week treatment phase, and 1-week follow
      up. Adult patients with CC (<=2 spontaneous bowel movements per week) received 2
      mg prucalopride or placebo, once-daily, for 12 weeks. Primary efficacy measure
      was percentage of patients with average of >=3 spontaneous complete bowel
      movements (SCBMs) per week (Responders) during the 12-week treatment. A key
      secondary endpoint was Responders during first 4 weeks of treatment. Other
      efficacy assessments were based on patient diaries, their assessments of symptoms
      and quality of life, and investigator's assessment on efficacy of treatment.
      Safety assessments included adverse events, laboratory values, and cardiovascular
      events. KEY RESULTS: Efficacy and safety were evaluated for 501 patients who
      received study drug. On the primary endpoint, prucalopride was significantly more
      effective than placebo with 83 (33.3%) vs 26 (10.3%) patients having a weekly
      average of >=3 SCBMs during the 12-week treatment (P < 0.001). Respective
      percentages were 34.5%vs 11.1% over first 4 weeks (P < 0.001). On other secondary
      endpoints, clinical improvement was generally larger and statistically superior
      (P < 0.001) in the prucalopride group. Most frequently reported adverse events
      were diarrhea, nausea, abdominal pain, and headache. CONCLUSION & INFERENCES:
      Prucalopride 2 mg given once-daily significantly improved bowel function,
      associated symptoms, and satisfaction in CC over a 12-week treatment period, and
      was safe and well tolerated by patients in the Asia-Pacific region.

PMID- 22882725
TI  - Utilization of intravenous thrombolysis is increasing in the United States.
AB  - BACKGROUND: Evaluating recombinant tissue plasminogen activator utilization rates
      is important, as many studies have demonstrated that administration of
      recombinant tissue plasminogen activator to qualified patients significantly
      improves prognosis. AIMS: We investigated recent trends in the utilization and
      outcomes of administration of intravenous recombinant tissue plasminogen
      activator in the United States using the National Inpatient Sample between 2001
      and 2008. METHODS: We identified patients with a primary diagnosis of acute
      ischemic stroke who underwent treatment with intravenous recombinant tissue
      plasminogen activator and studied utilization rates and clinical outcomes:
      discharge to long-term facility (morbidity), in-hospital death (mortality), and
      intracranial hemorrhage. Information on demographics, hospital characteristics,
      and comorbidities was collected. A multivariate logistic regression analysis was
      performed to determine independent predictors of morbidity, mortality, and
      intracranial hemorrhage. RESULTS: Intravenous recombinant tissue plasminogen
      activator utilization increased from 1.3% in 2001 to 3.5% in 2008. On
      multivariate analysis, variables associated with increased morbidity after
      intravenous recombinant tissue plasminogen activator administration included
      advanced age (P < 0.001), female gender (P < 0.001), and comorbidities of atrial
      fibrillation (P < 0.001) and hypertension (P < 0.001). Increased mortality was
      associated with increased age (P < 0.001) and comorbidities of atrial
      fibrillation, congestive heart failure, coronary artery disease, and diabetes (P
      < 0.001 for all comorbidities). CONCLUSIONS: Intravenous recombinant tissue
      plasminogen activator utilization rates increased between 2001 and 2008. Advanced
      age and atrial fibrillation were significantly associated with increased
      morbidity and mortality among patients treated with intravenous recombinant
      tissue plasminogen activator.

PMID- 22882726
TI  - Making death 'good': instructional tales for dying in newspaper accounts of Jade
      Goody's death.
AB  - Facilitating a 'good' death is a central goal for hospices and palliative care
      organisations. The key features of such a death include an acceptance of death,
      an open awareness of and communication about death, the settling of practical and
      interpersonal business, the reduction of suffering and pain, and the enhancement
      of autonomy, choice and control. Yet deaths are inherently neither good nor bad;
      they require cultural labour to be 'made over' as good. Drawing on media accounts
      of the controversial death of UK reality television star Jade Goody, and building
      on existing analyses of her death, we examine how cultural discourses actively
      work to construct deaths as good or bad and to position the dying and those
      witnessing their death as morally accountable. By constructing Goody as bravely
      breaking social taboos by openly acknowledging death, by contextualising her
      dying as occurring at the end of a life well lived and by emphasising
      biographical continuity and agency, newspaper accounts serve to position
      themselves as educative rather than exploitative, and readers as information
      seekers rather than ghoulishly voyeuristic. We argue that popular culture offers
      moral instruction in dying well which resonates with the messages from palliative
      care. 

PMID- 22882727
TI  - CYP7A1 polymorphism influences the LDL cholesterol-lowering response to
      atorvastatin.
AB  - WHAT IS KNOWN AND OBJECTIVE: Response to the lipid-lowering effect of the statins
      is known to show significant inter-individual variability. Our aim was to
      investigate whether genetic variants of the CYP3A5 gene, CYP7A1 gene and ABCG8
      gene influence the lipid-lowering response to atorvastatin. METHODS: One hundred
      and seven unrelated Chinese Han hypercholesterolemia patients were recruited from
      among the inpatients and outpatients of Tangshan Gongren Hospital of Hebei,
      China. Three polymorphisms of the CYP3A5 gene, seven polymorphisms of the CYP7A1
      gene and seven polymorphisms of the ABCG8 gene were selected using a tagging
      single-nucleotide polymorphism (tSNP) strategy and genotyped using Snapshot
      platform. RESULTS: SNP rs8192870, located in the first intron of the CYP7A1 gene,
      was associated with the LDL level lowering response to atorvastatin. The LDL
      levels were reduced by 27.89% for the GG/GA genotype carriers and 35.26% for the
      AA genotype carriers, respectively, after atorvastatin treatment (P = 0.021). The
      significance remained after adjusting for covariates. In addition, we observed
      that rs4148222 in the 11th intron of the ABCG8 gene significantly associated with
      the baseline levels of HDL (P = 0.046). WHAT IS NEW AND CONCLUSION: CYP7A1 gene
      polymorphism influences the LDL-lowering effects of atorvastatin in Chinese Hans.
      If replicated by others, identification of the tagged functional variant would be
      needed.

PMID- 22882728
TI  - Psychotropic drug use and alcohol drinking in community-dwelling older Australian
      men: the CHAMP study.
AB  - AIM: To explore the association between psychotropic drug use and alcohol
      drinking in community-dwelling older Australian men. DESIGN AND METHODS: We
      conducted a cross-sectional population-based study using baseline data collected
      between 2005 and 2007 from 1705 participants in the Concord Health and Ageing in
      Men Project (CHAMP) conducted in Sydney, Australia. All participants were men
      aged >=70 years. The prevalence of antidepressant and sedative or anxiolytic drug
      use was ascertained at clinical examinations and alcohol drinking was self
      reported. Logistic regression models were used to compute the unadjusted and
      adjusted prevalence ratios and 95% confidence intervals for the association
      between sedative or anxiolytic use and antidepressant use with drinking patterns.
      RESULTS: In the study sample, 8.0% used an antidepressant, 5.7% used a sedative
      or anxiolytic, 33.7% were daily drinkers, 13.9% were binge drinkers, 19.2% were
      heavy drinkers and 11.0% were problem drinkers. Overall, 27.1% of antidepressant
      users were daily drinkers and 42.7% of sedative or anxiolytic users were daily
      drinkers. Sedative or anxiolytic use was associated with daily drinking
      (prevalence ratio = 1.42; 95% confidence intervals 1.09-1.76) but not with other
      drinking patterns. The associations between antidepressant use and alcohol
      drinking were not statistically significant. DISCUSSION AND CONCLUSIONS:
      Potential psychotropic drug-alcohol interactions were common in older Australian
      men. Users of sedative or anxiolytic drugs were more likely to engage in daily
      drinking compared with non-users of sedative or anxiolytic drugs. Clinicians
      should monitor patients prescribed sedative or anxiolytic drugs for possible
      adverse events arising from concomitant use with alcohol.

PMID- 22882729
TI  - Family caregiver perspectives on social relations of elderly residents with
      dementia in small-scale versus traditional long-term care settings in the
      Netherlands and Belgium.
AB  - AIMS AND OBJECTIVES: To provide insight into family caregiver perspectives on
      social relations within the 'caregiving triangle' between family caregiver,
      professional caregiver and elderly resident with dementia. Results were compared
      between traditional versus small-scale long-term care settings in the Netherlands
      and Belgium. BACKGROUND: Residential dementia care is shifting towards a more
      holistic and person-centred approach. Until now, little is known about family
      caregiver perspectives. DESIGN: A quasi-experimental longitudinal design.
      METHODS: This study was part of a larger research project focusing on the quality
      of life of residents with dementia in traditional and small-scale settings (n =
      179). This study focused on family caregivers related to these residents (n =
      64). They filled in a questionnaire containing 25 items (baseline and after 12
      months) related to their perspectives on the interaction within the 'caregiving
      triangle'. Analyses were performed using mixed models and logistic regression.
      RESULTS: Compared to traditional settings, family caregivers of relatives with
      dementia living in small-scale settings had more contact with the professional
      caregivers, were more satisfied with this contact and felt that staff paid more
      attention to their feelings as family members. They also reported that staff
      showed better listening skills towards the residents. Furthermore, compared to
      those in Belgium, family caregivers in the Netherlands perceived staff to be less
      hurried and more accepting of help from family and felt that staff more often
      takes the resident seriously. CONCLUSION: In the move towards more person-centred
      care for residents with dementia, this study finds preliminary evidence for the
      importance of integrating the family perspective. RELEVANCE TO CLINICAL PRACTICE:
      Gaining more insight into the perspectives of family caregivers on the social
      relations within the 'caregiving triangle' may provide knowledge about the
      importance of the social system surrounding elderly residents with dementia and
      can provide pointers for future research.

PMID- 22882730
TI  - Sex hormone-binding globulin levels are not causally related to venous thrombosis
      risk in women not using hormonal contraceptives.
AB  - BACKGROUND: Oral contraceptive use increases the risk of venous thrombosis as
      well as sex hormone-binding globulin (SHBG) levels. Furthermore, increased SHBG
      levels are positively associated with activated protein C (APC) resistance and
      thrombotic risk in oral contraceptive users. OBJECTIVES: To determine whether
      increased SHBG levels are causally related to venous thrombosis in women not
      using hormonal contraceptives. METHODS: Premenopausal women were selected from a
      case-control study on venous thrombosis, the Multiple Environmental and Genetic
      Assessment of risk factors for venous thrombosis (MEGA) study (23 patients; 258
      controls). Women using hormonal contraceptives were excluded. First, the risk of
      venous thrombosis with SHBG levels above the normal reference range (70 nm) was
      determined. Second, because multiple regulatory factors affect SHBG levels and
      residual confounding may remain, we determined six single-nucleotide
      polymorphisms (SNPs) in the SHBG gene and assessed the risk of venous thrombosis
      in a different case-control study, the Leiden Thrombophilia Study (LETS) (20
      patients; 74 controls), and in the MEGA study. Finally, the association between
      SHBG levels and the normalized activated partial thromboplastin time-based APC
      resistance (an intermediate endpoint for venous thrombosis) was determined.
      RESULTS: Elevated SHBG levels (> 70.0 nm) were associated with venous thrombosis
      (odds ratio 1.92; 95% confidence interval [CI] 0.74-5.00). However, this finding
      can be explained by residual confounding. Two SNPs in the SHBG gene affected SHBG
      levels, but not venous thrombosis risk. Furthermore, SHBG levels in controls were
      not associated with APC resistance (SHBG level, > 70.0 vs. <= 70.0 nm: mean
      difference in normalized APC sensitivity ratio, 0.03; 95% CI -0.05 to 0.10).
      Exclusion of women with FV Leiden did not materially change these results.
      CONCLUSIONS: Increased SHBG levels are not causally related to the risk of venous
      thrombosis.

PMID- 22882731
TI  - Oncocytic lipoadenomatous tumours of salivary glands.

PMID- 22882732
TI  - Regional citrate anticoagulation in CVVH: a new protocol combining citrate
      solution with a phosphate-containing replacement fluid.
AB  - Regional citrate anticoagulation (RCA) is a valid anticoagulation method in
      continuous renal replacement therapies (CRRT) and different combination of
      citrate and CRRT solutions can affect acid-base balance. Regardless of the
      anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this
      case report, we evaluated safety and effects on acid-base balance of a new RCA-
      continuous veno-venous hemofiltration (CVVH) protocol using an 18 mmol/L citrate
      solution combined with a phosphate-containing replacement fluid. In our center,
      RCA-CVVH is routinely performed with a 12 mmol/L citrate solution and a
      postdilution replacement fluid with bicarbonate (protocol A). In case of
      persistent acidosis, not related to citrate accumulation, bicarbonate infusion is
      scheduled. In order to optimize buffers balance, a new protocol has been designed
      using recently introduced solutions: 18 mmol/L citrate solution, phosphate
      containing postdilution replacement fluid with bicarbonate (protocol B). In a
      cardiac surgery patient with acute kidney injury, acid-base status and
      electrolytes have been evaluated comparing protocol A (five circuits, 301 hours)
      vs. protocol B (two circuits, 97 hours): pH 7.39 +/- 0.03 vs. 7.44 +/- 0.03 (P <
      0.0001), bicarbonate 22.3 +/- 1.8 vs. 22.6 +/- 1.4 mmol/L (NS), Base excess -2.8
      +/- 2.1 vs. -1.6 +/- 1.2 (P = 0.007), phosphate 0.85 +/- 0.2 vs. 1.3 +/- 0.5
      mmol/L (P = 0.027). Protocol A required bicarbonate and sodium phosphate infusion
      (8.9 +/- 2.8 mmol/h and 5 g/day, respectively) while protocol B allowed to stop
      both supplementations. In comparison to protocol A, protocol B allowed to
      adequately control acid-base status without additional bicarbonate infusion and
      in absence of alkalosis, despite the use of a standard bicarbonate concentration
      replacement solution. Furthermore, the combination of a phosphate-containing
      replacement fluid appeared effective to prevent hypophosphatemia.

PMID- 22882733
TI  - Inflammatory linear verrucous epidermal nevus of the digits treated with surgical
      excision and skin grafting.

PMID- 22882734
TI  - Effect of the elderly and increasing injury severity on acute hospital resource
      utilization in a cohort of inner city trauma patients.
AB  - OBJECTIVE: This study aimed to determine the relative effect of elderly patients
      and increasing injury severity on acute hospital costs and inpatient length of
      stay. METHODS: A prospective study of all trauma team activations at a single
      inner city trauma centre was conducted over a 1-year period. Costs were imputed
      using Australian Refined Diagnosis-Related Groups. Costs and inpatient length of
      stays were compared between elderly (age >=65 years) and non-elderly patients.
      Relative effects of increasing injury severity score (ISS) and age categories
      were modelled using generalized linear regression. RESULTS: Over the study
      period, 1096 consecutive patients were studied. Falls were the most common
      mechanism and contributed the highest proportion of aggregate costs. There was a
      moderately high correlation between cost and ISS (Spearman's rank correlation
      coefficient 0.65, P < 0.001). Median costs for elderly patients were around three
      times higher than that for non-elderly patients and median length of stay was
      over twice that of non-elderly patients (7 days versus 3 days, P < 0.001). After
      adjusting for injury severity, the predicted costs of elderly trauma patients
      were around 30% higher compared with non-elderly patients. An increasing effect
      of injury severity on cost was observed across minor and major trauma.
      CONCLUSION: Both injury severity and elderly patients have a significant impact
      on acute hospital costs across the spectrum of major and minor trauma.

PMID- 22882735
TI  - A century of pneumococcal vaccination research in humans.
AB  - Sir Almroth Wright coordinated the first trial of a whole-cell pneumococcal
      vaccine in South Africa from 1911 to 1912. Wright started a chain of events that
      delivered pneumococcal vaccines of increasing clinical and public-health value,
      as medicine advanced from a vague understanding of the germ theory of disease to
      today's rational vaccine design. Early whole-cell pneumococcal vaccines mimicked
      early typhoid vaccines, as early pneumococcal antisera mimicked the first
      diphtheria antitoxins. Pneumococcal typing systems developed by Franz Neufeld and
      others led to serotype-specific whole-cell vaccines. Pivotally, Alphonse Dochez
      and Oswald Avery isolated pneumococcal capsular polysaccharides in 1916-17.
      Serial refinements permitted Colin MacLeod and Michael Heidelberger to conduct a
      1944-45 clinical trial of quadrivalent pneumococcal polysaccharide vaccine (PPV),
      demonstrating a high degree of efficacy in soldiers against pneumococcal
      pneumonia. Two hexavalent PPVs were licensed in 1947, but were little used as
      clinicians preferred therapy with new antibiotics, rather than pneumococcal
      disease prevention. Robert Austrian's recognition of high pneumococcal case
      fatality rates, even with antibiotic therapy, led to additional trials in South
      Africa, the USA and Papua New Guinea, with 14-valent and 23-valent PPVs licensed
      in 1977 and 1983 for adults and older children. Conjugation of polysaccharides to
      proteins led to several pneumococcal conjugate vaccines licensed since 2000,
      enabling immunization of infants and young children and resultant herd protection
      for all ages. Today, emergence of disease caused by pneumococcal serotypes not
      included in various vaccine formulations fuels research into conserved proteins
      or other means to maximize protection against more than 90 known pneumococcal
      serotypes.

PMID- 22882736
TI  - Visual attention to health warnings on plain tobacco packaging in adolescent
      smokers and non-smokers.
AB  - AIMS: Previous research with adults indicates that plain packaging increases
      visual attention to health warnings in adult non-smokers and weekly smokers, but
      not daily smokers. The present research extends this study to adolescents aged 14
      19 years. DESIGN: Mixed-model experimental design, with smoking status as a
      between-subjects factor and pack type (branded or plain pack) and eye gaze
      location (health warning or branding) as within-subjects factors. SETTING: Three
      secondary schools in Bristol, UK. PARTICIPANTS: A convenience sample of
      adolescents comprising never-smokers (n = 26), experimenters (n = 34), weekly
      smokers (n = 13) and daily smokers (n = 14). MEASUREMENTS: Number of eye
      movements to health warnings and branding on plain and branded packs. FINDINGS:
      Analysis of variance, irrespective of smoking status revealed more eye movements
      to health warnings than branding on plain packs, but an equal number of eye
      movements to both regions on branded packs (P = 0.033). This was observed among
      experimenters (P < 0.001) and weekly smokers (P = 0.047), but not among never
      smokers or daily smokers. CONCLUSION: Among experimenters and weekly smokers,
      plain packaging increases visual attention to health warnings and away from
      branding. Daily smokers, even relatively early in their smoking careers, seem to
      avoid the health warnings on cigarette packs. Adolescent never-smokers attend the
      health warnings preferentially on both types of packs, a finding which may
      reflect their decision not to smoke.

PMID- 22882737
TI  - What is known on angiogenesis-related rare diseases? A systematic review of
      literature.
AB  - Angiogenesis, the formation of new vessels from pre-existing ones, is essential
      during ontogenetic development and is related to many important physio
      pathological processes in the adult. In fact, a persistent and deregulated
      angiogenesis is a required event for many diseases and pathological situations,
      including cancer progression and metastasis. Some rare diseases are also
      angiogenesis-related pathologies. However, there is a lack of an exhaustive
      review on the topic. The main purpose of this work is to carry out a systematic
      review of literature to determine what (and how much) scientific information
      concerning angiogenesis-related rare diseases can be extracted from available
      sources. After exhaustive searches in bibliographic databases, preselected data
      were filtered by selecting only those articles on rare diseases with an Orpha
      number hosted in the Orphanet web. The selected bibliographic references were
      further curated manually. With the 187 selected references, a critical reading
      and analysis was carried out allowing for an identification and classification of
      angiogenesis-related rare diseases, the involved genes and the drugs available
      for their treatment, all on the basis of the information available in Orphanet
      database.

PMID- 22882738
TI  - Evaluation of the osteoconductive potential of bone substitutes embedded with
      schneiderian membrane- or maxillary bone marrow-derived osteoprogenitor cells.
AB  - AIM: Sinus augmentation procedures commonly employ osteoconductive scaffolding
      materials to stimulate and support bone formation. The aim of this study was to
      develop a simple screening methodology for the evaluation of the osteoconductive
      potential of various bone graft materials prior to clinical use. MATERIALS AND
      METHODS: Materials tested were Bio-Oss, Bi-Ostetic, OraGraft, and ProOsteon.
      These Simple and composite bone substitutes were embedded with osteoprogenitor
      cells derived from either the human maxillary sinus schneiderian membrane (hMSSM)
      or from maxillary tuberosity bone marrow and then monitored both in vitro and in
      vivo. RESULTS: Cell adherence and proliferation was most pronounced in OraGraft,
      followed by ProOsteon. In vivo bone formation, within the bone graft, was also
      observed, with most marked results in OraGraft and ProOsteon grafts. CONCLUSIONS:
      The proposed osteoconductivity testing method proved simple, informative, and
      reliable for the purpose of screening candidate biomaterials for sinus lifting or
      sinus augmentation.

PMID- 22882740
TI  - The effect of dietary long-chain omega-3 fatty acid supplementation on owner's
      perception of behaviour and locomotion in cats with naturally occurring
      osteoarthritis.
AB  - The aim of this randomized, double-blinded, placebo-controlled, cross-over
      designed study was to demonstrate the clinical effect, registered by a survey, of
      a 10-week period of omega-3 fatty acid supplementation of the diet (1.53 g
      eicosapentaenoic acid (EPA) and 0.31 g DHA, both per 1000 kcal ME, equivalent to
      the complete diet) of 16 cats with radiologically documented, naturally occurring
      osteoarthritis (OA), in comparison with a 10-week period of supplementation with
      corn oil (0.00 g EPA and 0.00 g DHA, both per 1000 kcal ME). Cats on the fish oil
      revealed higher activity level (p = 0.07), more walking up and down the stairs (p
      = 0.07), less stiffness during gait (p = 0.03), more interaction with the owner
      (p = 0.07) and higher jumps (p = 0.03) compared to those on corn oil
      supplementation. In conclusion, supplementation of long-chain omega-3
      polyunsaturated fatty acids changes the owner's perception of some aspects of
      behaviour and locomotion in cats with naturally occurring OA. 

PMID- 22882741
TI  - Fully automatic measuring system for assessing masticatory performance using beta
      carotene-containing gummy jelly.
AB  - Despite the importance of masticatory performance in health promotion, assessment
      of masticatory performance has not been widely conducted to date because the
      methods are labour intensive. The purpose of this study is to investigate the
      accuracy of a novel system for automatically measuring masticatory performance
      that uses beta-carotene-containing gummy jelly. To investigate the influence of
      rinsing time on comminuted jelly pieces expectorated from the oral cavity,
      divided jelly pieces were treated with two types of dye solution and then rinsed
      for various durations. Changes in photodiode (light receiver) voltages from light
      emitted through a solution of dissolved beta-carotene from jelly pieces under
      each condition were compared with those of unstained jelly. To investigate the
      influence of dissolving time, changes in light receiver voltage resulting from an
      increase in division number were compared between three dissolving times. For all
      forms of divided test jelly and rinsing times, no significant differences in
      light receiver voltage were observed between any of the stain groups and the
      control group. Voltages decreased in a similar manner for all forms of divided
      jelly as dissolving time increased. The highest coefficient of determination
      (R(2)  = 0.979) between the obtained voltage and the increased surface area of
      each divided jelly was seen at the 10 s dissolving time. These results suggested
      that our fully automatic system can estimate the increased surface area of
      comminuted gummy jelly as a parameter of masticatory performance with high
      accuracy after rinsing and dissolving operations of 10 s each.

PMID- 22882742
TI  - Accuracy of colposcopy-directed punch biopsies: a systematic review and meta
      analysis.
AB  - BACKGROUND: The colposcopy-directed punch biopsy is widely used in the management
      of women with abnormal cervical cytology; however, its accuracy compared with
      definitive histology from an excision biopsy is not well established. OBJECTIVES:
      To assess the accuracy of the colposcopy-directed punch biopsy to diagnose high
      grade cervical intraepithelial neoplasia (CIN) by performing a systematic review
      and meta-analysis. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and
      the Cochrane Library was performed. SELECTION CRITERIA: Articles that compared
      the colposcopically directed cervical punch biopsy with definitive histology from
      an excisional cervical biopsy or hysterectomy. DATA COLLECTION AND ANALYSIS:
      Random effects and hierarchical summary receiver operating characteristic
      regression models were used to compute the pooled sensitivity and specificity
      applying different test cut-offs for outcomes of high-grade CIN. MAIN RESULTS:
      Thirty-two papers comprising 7873 paired punch/definitive histology results were
      identified. The pooled sensitivity for a punch biopsy defined as test cut-off
      CIN1+ to diagnose CIN2+ disease was 91.3% (95% CI 85.3-94.9%) and the specificity
      was 24.6% (95% CI 16.0-35.9%). In most of the studies, the majority of enrolled
      women had positive punch biopsies. Pooling of the four studies where the excision
      biopsy was performed immediately after the punch biopsy, and where the rate of
      positive punch biopsies was considerably lower, yielded a sensitivity of 81.4%
      and specificity of 63.3%. AUTHOR'S CONCLUSION: The observed high sensitivity of
      the punch biopsy derived from all studies is probably the result of verification
      bias.

PMID- 22882743
TI  - Oncological outcomes after radical nephroureterectomy for upper tract urothelial
      carcinoma: comparison over the three decades.
AB  - OBJECTIVE: To evaluate temporal trends in clinicopathological features and
      oncological outcomes after radical nephroureterectomy for upper tract urothelial
      carcinoma. METHODS: Utilizing a multi-institutional database of patients treated
      with radical nephroureterectomy between 1983 and 2007, we compared
      clinicopathological features and survival outcomes over the past three decades
      using the following cohorts: group 1 comprised of patients treated before the
      1990s (n = 106), group 2 from 1990 to1999 (n = 655), and group 3 from 2000 to
      2007 (n = 701). Survival rates were compared using Kaplan-Meier survival
      analysis. RESULTS: The study included 1462 patients, 992 men and 470 women, with
      36 months median follow up (range 1-250 months) after radical nephroureterectomy.
      Tumors were organ confined (<=T2/N0) in 88% and high-grade in 64%. Neoadjuvant
      and adjuvant systemic chemotherapy was administered in 47 (3.2%) and 171 (11.7%)
      patients, respectively. There was a significant increase in the use of
      laparoscopic radical nephroureterectomy, endoscopic management of urothelial
      carcinoma and utilization of perioperative chemotherapy between decades 1 to 3.
      There were no significant differences in pathological stage distribution. The
      overall 5-year disease-free survival rates were 66 +/- 5%, 68.5 +/- 2% and 71 +/-
      2%, and the 5-year cancer-specific survival rates were 75 +/- 5%, 72 +/- 2%, and
      75 +/- 2% for groups 1, 2 and 3, respectively, with no significant statistical
      differences between the three decades (P > 0.05). CONCLUSION: Outcomes after
      radical nephroureterectomy have not changed significantly over the past three
      decades, despite staging and surgical refinements. Utilization of perioperative
      systemic chemotherapy in urothelial carcinoma management remains low. Further
      improvements in outcomes of urothelial carcinoma patients necessitate rigorous
      investigation of multimodal treatment approaches.

PMID- 22882744
TI  - Considering a complemental model of health and fitness.
AB  - This article examines the concept of fitness, which, in spite of its much avowed
      cultural significance, has become the subject of much critical attention. In
      particular, it considers the now contested relation of fitness to health; the
      fact that, although there appears to be a clear consensus on a simple causal
      relation between the two, this has been deemed illusory outside the medico
      scientific context of its production. In response to the problems with both of
      these positions, this article examines the potential for reconfiguring the
      relation between fitness and health on new terms. A complemental model of health
      and fitness is proposed; one that strives to account for the body's objective and
      subjective dimensions and for those intermediary varieties of experience that lie
      in between. 

PMID- 22882745
TI  - Idiopathic ventricular fibrillation originating from the moderator band.
AB  - We report a case of a 59-year-old man with idiopathic ventricular fibrillation
      storm. Ventricular fibrillation was pause-dependent and triggered by an early
      coupled right ventricular premature complex. The characteristic premature beat
      was mapped and successfully ablated from Purkinje fibers of the moderator band.

PMID- 22882746
TI  - Pre- and post-treatment with cyclosporine A in a rat model of transient focal
      cerebral ischaemia with multimodal MRI screening.
AB  - BACKGROUND: Irreversible damage may occur at reperfusion after sustained cerebral
      ischaemia. AIMS: We investigated the value of cyclosporine A for reducing the
      infarct size in a model of transient middle cerebral artery occlusion. METHODS:
      Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of
      one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during
      occlusion to confirm the success of surgery and measure baseline lesion size.
      Animals were randomly treated by: (i) intracarotid cyclosporine A (10 mg/kg) 20
      mins before middle cerebral artery occlusion (pretreatment group); (ii)
      intracarotid cyclosporine A (10 mg/kg) immediately after reperfusion (post
      treatment group); and (iii) intracarotid saline immediately after reperfusion.
      RESULTS: Histopathological measurements on day 1 showed a significant reduction
      of infarct size in the pretreatment group compared to the post-treatment
      (percentage values of ipsilateral hemispheres: 16 +/- 5% vs. 29 +/- 11%, P =
      0.004) and saline groups (16 +/- 5% vs. 42 +/- 12%, P = 0.015). No significant
      difference was observed between the post-treatment and saline groups (P = 0.065).
      Behavioural examinations on day 1 showed no significant difference between
      groups. Immunohistochemistry showed a statistically significant reduction of
      microglial cell count in the pretreatment group compared to either saline or
      cyclosporine A post-treatment groups. CONCLUSIONS: We conclude that intracarotid
      cyclosporine A is effective in reducing infarct size when given prior to
      ischaemia, but not when administered at reperfusion.

PMID- 22882747
TI  - MicroRNAs in metamorphic and non-metamorphic transitions in hemimetabolan insect
      metamorphosis.
AB  - BACKGROUND: Previous work showed that miRNAs play key roles in the regulation of
      metamorphosis in the hemimetabolan species Blattella germanica. To gain insight
      about which miRNAs might be important, we have constructed two miRNA libraries,
      one of the penultimate, pre-metamorphic nymphal instar (N5) and the other of the
      last, metamorphic nymphal instar (N6). RESULTS: High throughput sequencing gave
      61 canonical miRNAs present in the N5 and N6 libraries, although at different
      proportions in each. Comparison of both libraries led to the identification of
      three and 37 miRNAs significantly more expressed in N5 and N6 respectively.
      Twelve of these 40 miRNAs were then investigated further by qRT-PCR and results
      indicated that miR-252-3p was well expressed in N5 but not in N6, whereas let-7
      5p, miR-100-5p and miR-125-5p showed the reverse pattern. 20-Hydroxyecdysone
      (20E) tended to stimulate miRNA expression, whereas juvenile hormone (JH)
      inhibited the 20E stimulatory effect. Expression of let-7, miR-100 and miR-125
      was increased by 20E, which has also been observed in D. melanogaster. The only
      miRNA that was inhibited by 20E was miR-252-3p. The involvement of let-7, miR-100
      and miR-125 in metamorphosis has been demonstrated in other insects. Depletion of
      miR-252-3p caused growth and developmental delays, which suggests that this miRNA
      is involved in regulating these processes prior to metamorphosis. CONCLUSIONS:
      The comparative analysis of miRNA libraries from pre-metamorphic (N5) and
      metamorphic stages (N6) of B. germanica proved to be a useful tool to identify
      miRNAs with roles in hemimetabolan metamorphosis. Three miRNAs emerged as
      important factors in the metamorphic stage (N6): let-7-5p, miR-100-5p and miR-125
      5p, whereas miR-252-3p appears to be important in the pre-metamorphic stage (N5).

PMID- 22882748
TI  - Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of
      aspirin.
AB  - WHAT IS KNOWN AND OBJECTIVE: It has been reported that ibuprofen interferes with
      the antiplatelet effect of low-dose aspirin. This interaction is ascribed to
      steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when
      aspirin is administered after ibuprofen. However, whether other non-steroidal
      anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well
      defined. The aim of this study was to assess the influence of nine NSAIDs on the
      antiplatelet effect of aspirin. METHODS: We investigated the antiplatelet effect
      of NSAIDs using steady-state plasma concentration reported after usual doses. We
      studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin
      before NSAID addition and aspirin after NSAID addition to platelet-rich plasma.
      The rates of platelet aggregation induced by collagen were determined. The final
      concentration of aspirin used was the 50% effective concentration (EC(50))
      previously estimated in vitro. RESULTS AND DISCUSSION: Ibuprofen and mefenamic
      acid interfere with the antiplatelet effect of aspirin when added before the
      latter. The rate of platelet aggregation was reduced by 48.1% and 22.7%,
      respectively. The other NSAIDs tested did not significantly affect the aspirin
      antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs
      altered the aspirin effect if administration followed that of aspirin. WHAT IS
      NEW AND CONCLUSION: Naproxen and flurbiprofen have significant antiplatelet
      effects at plasma concentrations seen with usual doses. Our in vitro model
      suggests that the antiplatelet effect of aspirin is significantly diminished when
      taken after, but not before, ibuprofen or mefenamic acid. None of the other
      NSAIDs tested had any effect irrespective of the timing of dosing.

PMID- 22882749
TI  - GNB3 C825T polymorphism is associated with postural tachycardia syndrome in
      children.
AB  - AIM: Postural tachycardia syndrome (POTS) is one of the most frequent forms of
      chronic orthostatic intolerance in children and adolescents. The aim of the
      present study was to examine the influence of a genetic background on POTS.
      METHODS: A total of 96 children and adolescents with orthostatic dysregulation
      were studied. The polymorphism of the G protein beta3 subunit (GNB3) C825T and G
      protein alpha subunit (GNAS1) T131C of genes encoding components of the autonomic
      nervous system were determined and compared with circulatory responses to active
      standing. RESULTS: In the GNB3 gene C825T polymorphism, the CT and TT genotype
      had a significant lower supine heart rate and a larger increase of heart rate by
      standing than the CC, associated with evaluated power of the high-frequency
      component of heart rate variability. According to the criteria of the Japanese
      clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal
      responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT
      genotype was more frequently found in the POTS group (45.8%) than in the SD group
      (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for
      the T393C polymorphisms of GNA1 did not differ significantly between the groups.
      CONCLUSION: The gene polymorphisms GNB3 C825T might be a risk factor for POTS
      through the enhanced vagal withdrawal of the heart in children and adolescents.

PMID- 22882751
TI  - Adherence and medication management by the elderly.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to explore the strategies used
      for medication management by elderly who live at home. BACKGROUND: Non-adherence
      to chronic medication is a common problem among the elderly with chronic
      conditions. Many studies have been developed, but it did not progress in solving
      this multidisciplinary health care problem. The causes of non-adherence by the
      elderly are multiple and complex. DESIGN: Descriptive qualitative design.
      METHODS: Data were collected by two focus groups. The content of discussion was
      analysed from verbatim transcript and identifying categories and sub-categories
      emerged, leading to the construction of a diagram analysis. RESULTS: The finding
      indicated the strategies and the interpretation of people aged 65 or more and
      with chronic illness, managing their medication. Four content categories emerged:
      to live with drugs, taking medication, belief about drugs and relationship with
      health professionals. CONCLUSION: The study enabled us to identify and
      understand, by giving a 'voice' to the elderly, that living with drugs is a
      dynamic and complex process and that taking medication is perceived by older
      people as a consequence of their ageing, which requires them to include that
      process in their lives as a habit implying changes in their daily routines. The
      elderly suggest that the relationship with health professionals is essential in
      medication management and they reported that the information given by the nurse
      during consultation is very important. RELEVANCE TO CLINICAL PRACTICE: The
      relationship with nurses in particular is an important issue for the older
      people. Understanding the factors of adherence and helping people are important
      areas of research in nursing. The quality of this relationship may be the key to
      increasing adherence in this group of people.

PMID- 22882750
TI  - Everolimus with reduced tacrolimus improves renal function in de novo liver
      transplant recipients: a randomized controlled trial.
AB  - In a prospective, multicenter, open-label study, de novo liver transplant
      patients were randomized at day 30+/-5 to (i) everolimus initiation with
      tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced
      exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC
      Control). Randomization to TAC Elimination was terminated prematurely due to a
      higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was
      noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss
      or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7,
      2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of
      EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in
      adjusted estimated GFR from randomization to month 12 was superior with
      EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI
      3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for
      adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls
      (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections
      between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03,
      3.00). Everolimus facilitates early tacrolimus minimization with comparable
      efficacy and superior renal function, compared to a standard tacrolimus exposure
      regimen 12 months after liver transplantation.

PMID- 22882752
TI  - Patient experiences and preferences on short daily and nocturnal home
      hemodialysis.
AB  - Quotidian/intensive hemodialysis (short daily and nocturnal) has variable effects
      on health-related quality of life (HRQOL) as measured by standard HRQOL tools. We
      sought to understand the perceived benefits and limitations of quotidian dialysis
      by interviewing patients who had switched from conventional to home quotidian
      dialysis. We used a qualitative, phenomenological approach to explore the
      perceived benefits of quotidian dialysis from 10 patients using either short
      daily or nocturnal hemodialysis at a tertiary health care center in London,
      Canada. The patients varied in gender, age, employment status, home support,
      physical capacity, primary cause of kidney disease, previous forms of renal
      replacement therapy, and level of education. Four major themes emerged: (1)
      improvement in physical and mental well-being including better blood pressure and
      concentration, (2) increased control over patient's own life including time
      availability, choosing when to dialyze, and dialyzing at home, (3) decreased
      perception of being sick including returning to regular employment and avoiding
      sicker patients who must have in-center dialysis, and (4) identification of the
      competencies and supports required for quotidian dialysis including ability to
      provide self-care, supportive family, and medical support. Our findings suggest
      when patients' willingness and physical ability to use quotidian dialysis are
      coupled with education and support systems to assist patients' and families' self
      directed care, patients qualitatively perceive benefits of both increased
      physical and mental health, both measures of health-related quality of life.

PMID- 22882753
TI  - Influence of sumatriptan on gastric accommodation and on antral contraction in
      healthy subjects assessed by ultrasonography.
AB  - BACKGROUND: Oral sumatriptan administration has been reported to delay gastric
      emptying after liquid meals. The aim of this study was to determine whether
      delayed gastric emptying is caused by enhanced gastric accommodation, impaired
      antral contractions, or both using ultrasonography. METHODS: Ten healthy
      volunteers were enrolled in this randomized two-way crossover study. After
      overnight fasting, the subjects received the liquid meal 60 min after ingesting a
      50 mg sumatriptan tablet with 50 mL of water or 50 mL of water alone (control).
      The cross-sectional area of the proximal stomach was measured in a supine
      position after every 100 mL. The frequency and amplitude of the antral
      contractions were measured in a slightly backward sitting position. The
      intragastric distribution of the liquid meal was assessed by calculating the
      proximal stomach/distal stomach ratio (prox/distal ratio). KEY RESULTS: The cross
      sectional area after drinking 100, 200, and 300 mL of the liquid meal (oral
      sumatriptan vs control) was 34.49 vs 15.11 cm(2) (P = 0.0051), 48.00 vs 30.61
      cm(2) (P = 0.0166), and 58.67 vs 47.19 cm(2) (P = 0.0125), respectively. There
      was no significant difference in the amplitude of contractions, contraction
      cycle, motility index, and prox/distal ratio (97.15 vs 97.93%, P = 0.0745; 19.42
      vs 19.5 s, P= 0.8590; and 887.58 vs 889.22, P = 0.5751; 9.75 vs 8.41, P = 0.8785;
      respectively). CONCLUSIONS & INFERENCES: Oral sumatriptan administration enhanced
      gastric accommodation after the ingestion of liquid nutrients, but had no
      significant effect on antral contractions or intragastric distribution in healthy
      subjects.

PMID- 22882754
TI  - Immune-mediated interface dermatitis in a rhesus macaque.
AB  - BACKGROUND: Autoimmune dermatitis, specifically interface dermatitis, is rarely
      reported in nonhuman primates. RESULTS AND CONCLUSIONS: This report describes a
      case of idiopathic immune-mediated dermatitis clinically manifesting as
      palmoplantar hyperkeratosis in a rhesus macaque, successfully controlled with the
      use of long-term oral corticosteroid therapy.

PMID- 22882756
TI  - The accuracy of the International Normalized Ratio and the American College of
      Chest Physicians recommendations on the use of vitamin K to reverse over
      anticoagulation.

PMID- 22882755
TI  - Clinical and psychosocial remission in schizophrenia: correlations with
      antipsychotic treatment.
AB  - BACKGROUND: Clinical and psychosocial remission amongst persons with
      schizophrenia is nowadays a defined goal of treatment. This necessitates
      incorporating quantifiable psychosocial variables with traditional symptomatic
      data. We aimed to assess clinical and psychosocial remission in schizophrenia in
      a large cohort of community dwelling persons with schizophrenia. We emphasized
      between-groups comparison of antipsychotic medications and administration methods
      on the outcome of remission. METHODS: Psychiatric case managers rated
      psychosocial remission using the PsychoSocial Remission Scale (PSRS) and clinical
      remission using the Remission in Schizophrenia Working Group symptomatic
      remission criteria (RSWG). Ratings were performed for persons with schizophrenia
      they have been treating for 6 months or more. Data as to gender, age and
      pharmacological treatment of each patient were also collected. RESULTS: Of 445
      participants who completed the survey, 268 (60%) were evaluated by psychiatrists,
      161 (36%) by nurses and 16 (4%) were evaluated by social workers. Patients mean
      age was 43.4 + 13.1 years; 61% were men and 39% were women. Antipsychotic
      treatments were as follows: Per-os (PO) 243 (55%), IM long-acting typical
      antipsychotics (LAT) 102 (23%) and IM long-acting risperidone (RLAI; Consta) 100
      (22%). Overall, 37% of patients achieved symptomatic remission and 31% achieved
      psychosocial remission. Rates of symptomatic remission were significantly higher
      in patients treated by LAT and RLAI compared with PO (51% and 48% vs., 29%
      respectively, p = 0.0003). Rates of psychosocial remission were also
      significantly higher in patients treated by LAT and RLAI compared with PO (43%%
      and 41% vs., 24% respectively, p = 0.003). CONCLUSION: In a large national sample
      a third of persons with schizophrenia were in remission. IM long acting
      preparations were associated with higher remission rates. Treatment choice may
      thus influence rates of remission in persons with schizophrenia.

PMID- 22882757
TI  - GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic
      potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in
      rats.
AB  - AIM OF THE STUDY: This study was made to investigate the antidiabetic,
      antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees &
      Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along
      with evaluation of chemical constituents. MATERIALS AND METHODS: The GC-MS (Gas
      chromatography-mass spectrometry) analysis of the oil showed 31 constituents of
      which cinnamaldehyde was found the major component (44.898%). CTO and
      cinnamaldehyde was orally administered to diabetic rats to study its effect in
      both acute and chronic antihyperglycemic models. The body weight, oral glucose
      tolerance test and biochemical parameters viz. glucose level, insulin level,
      liver glycogen content, glycosylated hemoglobin, total plasma cholesterol,
      triglyceride and antioxidant parameters were estimated for all treated groups and
      compared against diabetic control group. RESULTS: CTO (100 mg/kg and 200 mg/kg),
      cinnamaldehyde (20 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of
      diabetic animals administered for 28 days reduced the blood glucose level in
      streptozotocin induced diabetic rats. There was significant increase in body
      weight, liver glycogen content, plasma insulin level and decrease in the blood
      glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as
      compared to control group. The results of CTO and cinnamaldehyde were found
      comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO
      using various models showed significant antioxidant activity. In vivo antioxidant
      studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and
      increased reduced glutathione (GSH). CONCLUSION: Thus the investigation results
      that CTO has significant antidiabetic, antioxidant and hypolipidemic activity.

PMID- 22882759
TI  - Increased doses of vaginal progesterone for the prevention of preterm birth in
      twin pregnancies: a randomised controlled double-blind multicentre trial.
AB  - OBJECTIVE: Previous trials have shown little benefit for preventing preterm birth
      in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher
      doses have not been tested. Our aim was to determine the efficacy and safety of
      two different daily doses of vaginal natural progesterone (200 and 400 mg),
      compared with placebo, for preventing preterm birth in unselected twin
      pregnancies. DESIGN: Randomised controlled double-blind multicentre trial
      (1:1:1). SETTING: The study was carried out in five university centres from
      Valencia, Murcia and Alicante (Spain). POPULATION: Women with dichorionic
      diamniotic twin pregnancies. METHODS: The women self-inserted two vaginal
      pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n =
      97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation
      or delivery. Randomisation was performed by an external centre. Data were
      analysed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Preterm birth
      rate. RESULTS: The baseline characteristics for placebo and progesterone groups
      were similar. Comparison of the three groups and analysis of progesterone-treated
      versus untreated women showed similar pregnancy and neonatal outcomes. The
      proportion of preterm and very preterm births, low birthweight, perinatal
      mortality and neonatal morbidity showed no differences between the three groups.
      Similar results were also obtained when comparing the 200- versus 400-mg
      progesterone groups. No serious adverse effects were encountered. CONCLUSIONS:
      Vaginal progesterone therapy was generally well tolerated, but failed to prevent
      preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg
      progesterone dose offered no advantages over the 200-mg regimen.

PMID- 22882758
TI  - Perivascular cells for regenerative medicine.
AB  - Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic
      cells for regenerative medicine related to osteoarticular, muscular, vascular and
      inflammatory diseases, although these cells remain heterogeneous and necessitate
      a better biological characterization. We and others recently described that MSC
      originate from two types of perivascular cells, namely pericytes and adventitial
      cells and contain the in situ counterpart of MSC in developing and adult human
      organs, which can be prospectively purified using well defined cell surface
      markers. Pericytes encircle endothelial cells of capillaries and microvessels and
      express the adhesion molecule CD146 and the PDGFRbeta, but lack endothelial and
      haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the
      ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is
      a pericyte marker exclusively associated with the arterial system. Besides its
      expression in smooth muscle cells, smooth muscle actin (alphaSMA) is also
      detected in subsets of pericytes. Adventitial cells surround the largest vessels
      and, opposite to pericytes, are not closely associated to endothelial cells.
      Adventitial cells express CD34 and lack alphaSMA and all endothelial and
      haematopoietic cell markers, as for pericytes. Altogether, pericytes and
      adventitial perivascular cells express in situ and in culture markers of MSC and
      display capacities to differentiate towards osteogenic, adipogenic and
      chondrogenic cell lineages. Importantly, adventitial cells can differentiate into
      pericyte-like cells under inductive conditions in vitro. Altogether, using
      purified perivascular cells instead of MSC may bring higher benefits to
      regenerative medicine, including the possibility, for the first time, to use
      these cells uncultured.

PMID- 22882760
TI  - No evidence of a death-like function for species B1 human adenovirus type 3 E3-9K
      during A549 cell line infection.
AB  - BACKGROUND: Subspecies B1 human adenoviruses (HAdV-B1) are prevalent respiratory
      pathogens. Compared to their species C (HAdV-C) counterparts, relatively little
      work has been devoted to the characterization of their unique molecular biology.
      The early region 3 (E3) transcription unit is an interesting target for future
      efforts because of its species-specific diversity in genetic content among
      adenoviruses. This diversity is particularly significant for the subset of E3
      encoded products that are membrane glycoproteins and may account for the distinct
      pathobiology of the different human adenovirus species. In order to understand
      the role of HAdV-B-specific genes in viral pathogenesis, we initiated the
      characterization of unique E3 genes. As a continuation of our efforts to define
      the function encoded in the highly polymorphic ORF E3-10.9K and testing the
      hypothesis that the E3-10.9K protein orthologs with a hydrophobic domain
      contribute to the efficient release of viral progeny, we generated HAdV-3 mutant
      viruses unable to express E3-10.9K ortholog E3-9K and examined their ability to
      grow, disseminate, and egress in cell culture. RESULTS: No differences were
      observed in the kinetics of infected cell death, and virus progeny release or in
      the plaque size and dissemination phenotypes between cells infected with HAdV-3
      E3-9K mutants or the parental virus. The ectopic expression of E3-10.9K orthologs
      with a hydrophobic domain did not compromise cell viability. CONCLUSIONS: Our
      data show that despite the remarkable similarities with HAdV-C E3-11.6K, HAdV-B1
      ORF E3-10.9K does not encode a product with a "death-like" biological activity.

PMID- 22882761
TI  - Comparison of two inside-out transobturator suburethral sling techniques for
      stress incontinence: early postoperative thigh pain and 3-year outcomes.
AB  - OBJECTIVES: Inside-out tension-free vaginal tape obturators for the cure of
      female stress incontinence can cause postoperative thigh pain. The aim of the
      present study was to analyze and compare the mid-term outcomes of two tension
      free vaginal tape obturator procedures. METHODS: Patients diagnosed with urinary
      stress incontinence were enrolled to undergo a tension-free vaginal tape
      obturator sub-mid urethral tape operation either by de-Leval's method or by
      Flam's modification. Peri- and postoperative data were collected by uninvolved
      researchers and analyzed. Follow up was 36 months. RESULTS: Overall, 161 patients
      were included in the study. Cure and complication rates were similar between the
      two treatment groups. Postoperative thigh pain was significantly more frequent
      and lasted longer in the de-Leval group compared with the Flam group (31.9% vs
      10.0%, respectively). Urinary urgency was more frequent in the de-Leval patients
      (20.3% vs 2.8%). CONCLUSION: Our findings suggest that both tension-free vaginal
      tape obturator procedures are effective with few adverse effects. The Flam method
      provides shorter and decreased levels of postoperative thigh pain, as well as
      reduced long-term postoperative urinary urgency.

PMID- 22882762
TI  - Induction of allograft tolerance by monoclonal CD3 antibodies: a matter of
      timing.
AB  - Despite remarkable progress in organ transplantation through the development of a
      wealth of immunosuppressive drugs highly effective at controlling acute
      rejection, two major problems still remain, the loss of transplants due to
      chronic rejection and the growing number of sensitized recipients due to previous
      transplants, transfusions or pregnancies. Induction of immune tolerance appears
      to be the only way to curb this complex situation. Here we describe that a
      therapy, already successfully used to restore immune tolerance to self-antigens
      in overt autoimmunity, is effective at promoting transplant tolerance. We
      demonstrate that a short low-dose course with CD3 antibodies started after
      transplantation, at the time of effector T cell priming to alloantigens, induces
      permanent acceptance of fully mismatched islet allografts. Mechanistic studies
      revealed that antigen-specific regulatory and effector T cells are differentially
      affected by the treatment. CD3 antibody treatment preferentially induces
      apoptosis of activated alloreactive T cells which is mandatory for tolerance
      induction. In contrast, regulatory T cells are relatively spared from CD3
      antibody-induced depletion and can transfer antigen-specific tolerance thus
      arguing for their prominent role in sustaining long-term graft survival.

PMID- 22882763
TI  - Muscle activation patterns during walking from transtibial amputees recorded
      within the residual limb-prosthetic interface.
AB  - BACKGROUND: Powered lower limb prostheses could be more functional if they had
      access to feedforward control signals from the user's nervous system. Myoelectric
      signals are one potential control source. The purpose of this study was to
      determine if muscle activation signals could be recorded from residual lower limb
      muscles within the prosthetic socket-limb interface during walking. METHODS: We
      recorded surface electromyography from three lower leg muscles (tibilias
      anterior, gastrocnemius medial head, gastrocnemius lateral head) and four upper
      leg muscles (vastus lateralis, rectus femoris, biceps femoris, and gluteus
      medius) of 12 unilateral transtibial amputee subjects and 12 non-amputee subjects
      during treadmill walking at 0.7, 1.0, 1.3, and 1.6 m/s. Muscle signals were
      recorded from the amputated leg of amputee subjects and the right leg of control
      subjects. For amputee subjects, lower leg muscle signals were recorded from
      within the limb-socket interface and from muscles above the knee. We quantified
      differences in the muscle activation profile between amputee and control groups
      during treadmill walking using cross-correlation analyses. We also assessed the
      step-to-step inter-subject variability of these profiles by calculating variance
      to-signal ratios. RESULTS: We found that amputee subjects demonstrated reliable
      muscle recruitment signals from residual lower leg muscles recorded within the
      prosthetic socket during walking, which were locked to particular phases of the
      gait cycle. However, muscle activation profile variability was higher for amputee
      subjects than for control subjects. CONCLUSION: Robotic lower limb prostheses
      could use myoelectric signals recorded from surface electrodes within the socket
      limb interface to derive feedforward commands from the amputee's nervous system.

PMID- 22882766
TI  - Louis Pasteur, from crystals of life to vaccination.
AB  - Louis Pasteur (1822-1895) is an exceptional scientist who opened a new era in
      medicine and biology. Starting from studies on crystals of by-products of wine
      fermentation, he first defined a distinct chemistry between dead and living
      matters. He then showed the role of living microbes in the fermentation and
      putrefaction processes. This brought him to challenge the two-millennium-old
      theory of spontaneous generation, using remarkably well-designed experiments. His
      observations on epidemics in silkworms allowed him to demonstrate the role of
      specific germs in infectious diseases. His discovery of the vaccine against fowl
      cholera can be considered as the birth of immunology. Finally, he became
      universally recognized through his famous vaccinations against anthrax and
      rabies.

PMID- 22882764
TI  - P2X7 receptor regulation of non-classical secretion from immune effector cells.
AB  - P2X7 receptors (P2X7R) are extracellular ATP-gated ion channels expressed in the
      immune effector cells that carry out critical protective responses during the
      early phases of microbial infection or acute tissue trauma. P2X7R-positive cells
      include monocytes, macrophages, dendritic cells and T cells. Given its presence
      in all host and pathogen cell types, ATP can be readily released into
      extracellular compartments at local sites of tissue damage and microbial
      invasion. Thus, extracellular ATP and its target receptors on host effector cells
      can be considered as additional elements of the innate immune system. In this
      regard, stimulation of P2X7R rapidly triggers a key step of the inflammatory
      response: induction of NLRP3/caspase-1 inflammasome signalling complexes that
      drive the proteolytic maturation and secretion of the proinflammatory cytokines
      interleukin-1beta (IL-1beta) and interleukin-18 (IL-18). IL-1beta (and IL-18)
      lacks a signal sequence for compartmentation within the Golgi and classical
      secretory vesicles and the proIL-1beta precursor accumulates within the cytosol
      following translation on free ribosomes. Thus, ATP-induced accumulation of the
      mature IL-1beta cytokine within extracellular compartments requires non-classical
      mechanisms of export from the cytosolic compartment. Five proposed mechanisms
      include: (i) exocytosis of secretory lysosomes that accumulate cytosolic IL-1beta
      via undefined protein transporters; (ii) release of membrane-delimited
      microvesicles derived from plasma membrane blebs formed by evaginationsof the
      surface membrane that entrap cytosolic IL-beta; (iii) release of membrane
      delimited exosomes secondary to the exocytosis of multivesicular bodies formed by
      invaginations of recycling endosomes that entrap cytosolic IL-beta; (iv)
      exocytosis of autophagosomes or autophagolysosomes that accumulate cytosolic IL
      1beta via entrapment during formation of the initial autophagic isolation
      membrane or omegasome and (v) direct release of cytosolic IL-1beta secondary to
      regulated cell death by pyroptosis or necroptosis. These mechanisms are not
      mutually exclusive and may represent engagement of parallel or intersecting
      membrane trafficking responses to P2X7R activation.

PMID- 22882767
TI  - Single purse string with four-point traction for better haemorrhoid retraction.
AB  - BACKGROUND: Traction method is important to stapled haemorrhoidopexy (SH) for its
      impact on haemorrhoidal prolapse reduction. Single purse string with one-point
      traction is most commonly used in SH. This traction method often results in an
      irregular mucosal doughnut with inadequate height, which leads to insignificant
      and uneven haemorrhoidal prolapse reduction. Single purse string with two-point
      traction is a modified traction method. According to some authors, it has
      significantly improved the height and regularity of the mucosal doughnut in SH.
      However, the reduction of haemorrhoidal prolapse is not always satisfactory,
      especially in patients with large prolapse. Our assumption is that single purse
      string with four-point traction, a more balanced traction method, will provide
      better control to increase the doughnut height using the same amount of traction.
      This study was designed to evaluate the outcomes of single purse string with four
      point traction as compared with two-point traction in SH. METHODS: Consecutive
      patients with symptomatic grade III haemorrhoids were randomized to two groups:
      Group 1, G(1) ; Group 2, G(2) . Each group underwent SH by colorectal surgeons.
      The patients in G(1) underwent single purse string with two-point traction. The
      patients in G(2) underwent SH using single purse string with four-point traction.
      Preoperative, intraoperative and post-operative patient characteristics were
      evaluated. RESULTS: Sixty patients with a median age of 44 (range, 21-78) years
      were identified. Patient demographic and clinical characteristics were similar in
      the two groups. The height of the mucosectomy specimens significantly increased
      in patients of G(2) (P < 0.01, t-test). The variation in mucosal doughnut height
      significantly decreased in patients of G(2) (P < 0.01, t-test). The anatomy score
      after SH also significantly decreased in patients of G (2) (P = 0.029, Mann
      Whitney U-test). No significant difference in complications was observed between
      the two groups. Median follow-up was 14 (range, 6-22) months. No haemorrhoidal
      symptoms were found in these patients. CONCLUSION: Single purse string with four
      point traction ensures a taller and more regular mucosal doughnut during SH, thus
      it brings a more satisfactory haemorrhoid retraction.

PMID- 22882768
TI  - Clinical significance of induced atrial tachycardia after termination of
      longstanding persistent atrial fibrillation using a stepwise approach.
AB  - INTRODUCTION: The utility of inducibility test of atrial tachycardia (AT) in
      patients with longstanding persistent atrial fibrillation (AF; LPAF) is unclear.
      This study aimed to evaluate the significance of induced AT and the impact of
      their ablation on the clinical outcome. METHODS: In 194 patients with LPAF (>1
      year) who underwent catheter ablation (pulmonary vein isolation with substrate
      ablation), an inducibility test was performed after AF termination. RESULTS: AT
      was induced in 108 (56%) patients (induced AT group); neither AT nor AF was
      inducible in 37 (19%, noninduction group). During 39 +/- 21 months, AT recurred
      in 30 patients (28%), AF in 19 (17%), and no arrhythmia in 56 (52%) among induced
      AT group, although there was a recurrence of AT in 9 (24%, P = 0.68), AF in 6
      (16%, P = 0.85), and no arrhythmia in 22 (60%, P = 0.42) among noninduction group
      (P = NS). Note that 10 patients with repeated ablation in induced AT group
      revealed 8 different and 2 similar recurrent ATs compared to the induced ATs at
      first session. The mean cycle length of induced AT that terminated by ablation
      (271 +/- 64 ms) was longer than that without (249 +/- 58 ms, P < 0.05). In
      induced AT group, AT recurrence rate in patients who achieved AT termination by
      ablation was lower than those without termination (5% vs 36%, P < 0.05).
      CONCLUSIONS: ATs that are inducible after LPAF termination do not necessarily
      become clinical AT. However, patients who achieved noninducibility of AT by
      ablating slower cycle length of AT had better outcomes.

PMID- 22882769
TI  - Treatment of preterm infants with West syndrome: differences due to etiology.
AB  - BACKGROUND: This study was conducted with a particular focus on preterm infants
      with West syndrome (WS) to evaluate differences in the first responses to oral
      medication based on etiology. METHODS: Medical records of 53 patients with WS,
      treated at five institutions between 2005 and 2009, were reviewed
      retrospectively. Patients were divided into six groups based on the time of brain
      insult, and evaluated for short-term outcomes using oral anti-epileptic agents
      and synthetic adrenocorticotropic hormone. RESULTS: The sample consisted of 15,
      six, 14, two, four, and 12 patients classified, on the basis of apparent time of
      acquisition of etiology, into the prenatal, term, preterm, postnatal, other, and
      no identified etiology groups, respectively. Average age of onset in the term
      group was 3.3 +/- 1.0 months, significantly earlier than in the prenatal,
      preterm, postnatal and no identified etiology groups (P < 0.05). All patients in
      the term group had experienced seizures before the onset of WS. Only patients in
      the preterm group had only experienced neonatal seizures, and responded better to
      treatment. Patients in the preterm group had better responses to treatment,
      especially oral medication, compared with those in the prenatal and term groups.
      The prevalence of relapse of seizures in the preterm group (14%) was
      significantly lower than that in the prenatal group. CONCLUSIONS: Preterm WS
      patients responded well to treatment. Distinguishing WS patients on the basis of
      different etiologies is important for evaluating the effectiveness of treatment.

PMID- 22882770
TI  - No effect of short-term exposure to high-fibre diets on the gastrointestinal
      morphology of layer hens (Gallus gallus domesticus): body reserves are used to
      manage energy deficits in favour of phenotypic plasticity.
AB  - Using layer hens, Gallus gallus domesticus, we compared the digestive
      capabilities of birds on a low-fibre diet (LF, 8.49% neutral detergent fibre;
      NDF), with those fed a high-fibre diet balanced for energy and protein to match
      the LF diet (high fibre balanced, HFB; NDF = 15.61%) and those fed a high fibre
      unbalanced (HFU) diet (NDF = 16.68%). The HFU diet had the lowest apparent dry
      matter (DM) metabolisability at 58.14 +/- 6.46%, followed by HFB, 65.87 +/- 3.50
      and the LF diet, 70.49 +/- 7.07%. Despite significant differences between
      apparent DM metabolisabilities of LF and HFU diets, no morphometric changes in
      the gastrointestinal tract (GIT) of layer hens were observed (including crop,
      gizzard, proventriculus, liver, large intestine, paired caeca and small
      intestine). Conversely, body mass losses were recorded for animals on HFU diet,
      while those on the LF and HFB diets actually gained body mass over the 14-day
      trials. We suggest that the body mass losses seen in the animals fed HFU diets
      were attributed to losses in adipose tissue, but this was not quantified.
      Assuming body mass losses were mainly in adipose tissue, we propose that adipose
      may act to buffer environmental challenges like shortfalls in nutrient
      acquisition when dietary energy requirements are not met. Compared with smaller
      birds (e.g. quail), the larger body size of the layer hens may offer them a
      greater safety margin in terms of body energy reserves before changes in the GIT
      might be needed to redress energy deficits associated with hard-to-digest, high
      fibre diets. 

PMID- 22882771
TI  - Twenty-five years of volatile substance abuse mortality: a national mortality
      surveillance programme.
AB  - AIMS: To investigate trends in volatile substance abuse (VSA) deaths over 25
      years. DESIGN: A national mortality surveillance programme with standardised data
      collection procedures. SETTING: The UK and islands. PARTICIPANTS/MEASUREMENTS:
      All VSA deaths, 1983-2007. FINDINGS: In the five quinquennia from 1983 to 2007
      the numbers of VSA deaths were 499, 609, 378, 349 and 258 respectively. There
      were gradual increases in the mean age at death in males and females and in the
      number of VSA deaths in women. Coincident with the 1992 Department of Health
      Advertising Campaign, VSA deaths in boys and girls (<18 years of age) fell by an
      estimated 56% (95% CI: 36%-70%) and 64% (20%-84%), respectively, from the
      underlying trend, but there was no evidence of any similar step change in either
      group following the 1999 Legislation prohibiting sales of cigarette lighter
      refills containing butane to those under the age of 18 years. Between 1983-1987
      and 2003-2007, the ratio of aerosol to gas fuel deaths fell by an estimated 80%
      (57% to 91%) in adults, while the ratio of glue to gas fuel deaths fell by an
      estimated 95% (89% to 97%) in adults and an estimated 87% (-1% to 98%) in
      children. CONCLUSIONS: Between 1983 and 2007, in the United Kingdom, the numbers
      of deaths associated with volatile substance abuse peaked in the early 1990s and
      fell to their lowest level in the mid-2000s. The age at death increased in both
      males and females. There was a fall in the proportion of volatile substance abuse
      deaths involving glues and a rise, particularly in adults, in the proportion
      involving gas fuels.

PMID- 22882772
TI  - Pyrosequencing-based analysis reveals a novel capsular gene cluster in a KPC
      producing Klebsiella pneumoniae clinical isolate identified in Brazil.
AB  - BACKGROUND: An important virulence factor of Klebsiella pneumoniae is the
      production of capsular polysaccharide (CPS), a thick mucus layer that allows for
      evasion of the host's defense and creates a barrier against antibacterial
      peptides. CPS production is driven mostly by the expression of genes located in a
      locus called cps, and the resulting structure is used to distinguish between
      different serotypes (K types). In this study, we report the unique genetic
      organization of the cps cluster from K. pneumoniae Kp13, a clinical isolate
      recovered during a large outbreak of nosocomial infections that occurred in a
      Brazilian teaching hospital. RESULTS: A pyrosequencing-based approach showed that
      the cps region of Kp13 (cpsKp13) is 26.4 kbp in length and contains genes common,
      although not universal, to other strains, such as the rmlBADC operon that codes
      for L-rhamnose synthesis. cpsKp13 also presents some unique features, like the
      inversion of the wzy gene and a unique repertoire of glycosyltransferases. In
      silico comparison of cpsKp13 RFLP pattern with 102 previously published cps PCR
      RFLP patterns showed that cpsKp13 is distinct from the C patterns of all other K
      serotypes. Furthermore, in vitro serotyping showed only a weak reaction with
      capsular types K9 and K34. We confirm that K9 cps shares common genes with
      cpsKp13 such as the rmlBADC operon, but lacks features like uge and Kp13-specific
      glycosyltransferases, while K34 capsules contain three of the five sugars that
      potentially form the Kp13 CPS. CONCLUSIONS: We report the first description of a
      cps cluster from a Brazilian clinical isolate of a KPC-producing K. pneumoniae.
      The gathered data including K-serotyping support that Kp13's K-antigen belongs to
      a novel capsular serotype. The CPS of Kp13 probably includes L-rhamnose and D
      galacturonate in its structure, among other residues. Because genes involved in L
      rhamnose biosynthesis are absent in humans, this pathway may represent potential
      targets for the development of antimicrobial agents. Studying the capsular
      serotypes of clinical isolates is of great importance for further development of
      vaccines and/or novel therapeutic agents. The distribution of K-types among
      multidrug-resistant isolates is unknown, but our findings may encourage
      scientists to perform K-antigen typing of KPC-producing strains worldwide.

PMID- 22882774
TI  - 'If you have a soul, you will volunteer at once': gendered expectations of duty
      to care during pandemics.
AB  - Duty to care has been identified as a pressing ethical issue in contemporary
      discussions of pandemic preparedness; however, nuanced discussions of this
      complicated issue are relatively limited. This article presents historical data
      from the experience of the 1918 influenza pandemic in Brantford, Ontario in
      Canada, demonstrating that, in the face of an actual pandemic, the particular
      construction of duty to care as both moral and gendered meant that women were
      placed at a greater personal risk during this time. Given that women still
      dominate the front lines of healthcare work, we argue that it is critical for
      current stakeholders to reflect on how these historical patterns may be
      replicated in contemporary pandemic planning and response.

PMID- 22882775
TI  - Testicular angina during hemodialysis: an unusual complication of
      ultrafiltration.
AB  - During hemodialysis, the development of hypotension or symptoms suggestive of
      ischemia is used as a surrogate marker for the establishment of dry weight. These
      symptoms manifest commonly as muscle cramps, chest pain or abdominal pain.
      Hemodialysis patients are also prone to vascular calcification which may be
      medial or intimal. We report the case of a 68-year-old male who developed
      testicular pain while attempting to establish dry weight. Computerized tomography
      scan of his abdomen showed extensive vascular calcification. The end result in
      this case was bilateral orchiectomy. Histopathology revealed hyperplastic
      arteriolosclerosis with intimal calcification contributing to ischemia.

PMID- 22882776
TI  - Implementation of an inpatient smoking cessation programme in a Veterans Affairs
      facility.
AB  - AIMS AND OBJECTIVES: To test the transportability and implementation of the
      Tobacco Tactics intervention using the Reach, Effectiveness, Adoption,
      Implementation and Maintenance framework, for inpatient units at the Jesse Brown
      Veterans Affairs Medical Center. BACKGROUND: Smoking rates are high among
      veterans. While the Department of Veterans Affairs has standardised outpatient
      cessation clinics, inpatient cessation services, known to be efficacious, are
      only sporadically provided. DESIGN: This was a phase 4, pre and
      postimplementation study of the Tobacco Tactics intervention. METHODS: A unique
      convenience sample of inpatient veteran smokers was recruited both before (n =
      54) and after (n = 50) implementation of the Tobacco Tactics programme.
      Participants completed baseline and 30-day follow-up surveys along with urine
      cotinine test kits. In addition, staff completed anonymous surveys during the
      preintervention period (n = 158) and two months after (n = 81) the Tobacco
      Tactics training. Bivariate analyses compared preintervention vs.
      postintervention patient and staff characteristics using Chi-square, Fisher's
      Exact or Student's t-test. p-values <0.05 were considered significant. RESULTS:
      Patient-reported receipt of services and satisfaction was 10% higher in the
      postintervention compared to the preintervention group. Quit rates were 3% higher
      in the postintervention than in the preintervention group. The mean number of
      cigarettes smoked per day increased from 13 to 15 in the preintervention group,
      while the mean number of cigarettes smoked per day decreased from 14 to 9 in the
      postintervention group. Staff's confidence in their ability to provide cessation
      services improved greatly posttraining (p = 0.0017) as did self-reported delivery
      of cessation services (p = 0.0154). CONCLUSIONS: With as little as one-hour
      training for nurses, the Tobacco Tactics intervention has the potential to be
      widely disseminated in the Department of Veterans Affairs. RELEVANCE TO CLINICAL
      PRACTICE: The implementation of inpatient smoking interventions has the potential
      to improve quit rates and decrease morbidity and mortality in the Department of
      Veterans Affairs.

PMID- 22882773
TI  - Topical application of phosphatidyl-inositol-3,5-bisphosphate for acute lung
      injury in neonatal swine.
AB  - Hypoxemic respiratory failure of the neonatal organism involves increased acid
      sphingomyelinase (aSMase) activity and production of ceramide, a second messenger
      of a pro-inflammatory pathway that promotes increased vascular permeability,
      surfactant alterations and alveolar epithelial apoptosis. We comparatively
      assessed the benefits of topical aSMase inhibition by either imipramine (Imi) or
      phosphatidylinositol-3,5-bisphosphate (PIP2) when administered into the airways
      together with surfactant (S) for fortification. In this translational study, a
      triple-hit acute lung injury model was used that entails repeated airway lavage,
      injurious ventilation and tracheal lipopolysaccharide instillation in newborn
      piglets subject to mechanical ventilation for 72 hrs. After randomization, we
      administered an air bolus (control), S, S+Imi, or S+PIP2. Only in the latter two
      groups we observed significantly improved oxygenation and ventilation, dynamic
      compliance and pulmonary oedema. S+Imi caused systemic aSMase suppression and
      ceramide reduction, whereas the S+PIP2 effect remained compartmentalized in the
      airways because of the molecule's bulky structure. The surfactant surface
      tensions improved by S+Imi and S+PIP2 interventions, but only to a minor extent
      by S alone. S+PIP2 inhibited the migration of monocyte-derived macrophages and
      granulocytes into airways by the reduction of CD14/CD18 expression on cell
      membranes and the expression of epidermal growth factors (amphiregulin and TGF
      beta1) and interleukin-6 as pro-fibrotic factors. Finally we observed reduced
      alveolar epithelial apoptosis, which was most apparent in S+PIP2 lungs. Exogenous
      surfactant "fortified" by PIP2, a naturally occurring surfactant component,
      improves lung function by topical suppression of aSMase, providing a potential
      treatment concept for neonates with hypoxemic respiratory failure.

PMID- 22882777
TI  - Growing trend in older patients with severe injuries: mortality and mechanisms of
      injury between 1991 and 2010 at an inner city major trauma centre.
AB  - BACKGROUND: Elderly patients with major trauma are an increasingly important
      public health concern. The objective of the study was to describe the long term
      trend in patients aged 65 years and older with major trauma. METHODS: A
      retrospective single centre trauma registry study conducted at an inner city
      Major Trauma Centre in Sydney. Data on patients aged 65 years or older with major
      trauma (Injury Severity Score greater than 15) presenting between 1991 and 2010
      were extracted from the data registry. Demographic data, mechanism of injury,
      injury severity scores and outcomes were collected. Study outcomes were
      proportion of total major trauma volume due to patients aged 65 years and older,
      in hospital mortality and total beddays occupied per year. RESULTS: The
      proportion of major trauma volume due to older patients increased by 4.9% per
      year currently accounting for a third of major trauma volume. The proportion of
      major trauma in older patients due to falls has also increased. Standardised
      mortality rates have declined by 2.2% per year. CONCLUSION: There has been a
      disproportionate increase in the proportion of major trauma due to older patients
      at this institution over the past twenty years. If this trend continues, it is
      likely to have significant impacts on future hospital and rehabilitation
      resources.

PMID- 22882778
TI  - Transient receptor potential vanilloid 4 blockade protects against experimental
      colitis in mice: a new strategy for inflammatory bowel diseases treatment?
AB  - Recent reports suggested that the activation of Transient Receptor Potential
      Vanilloid 4 (TRPV4) receptors in the gastrointestinal tract has pro-inflammatory
      effects. In this study, we demonstrated for the first time that TRPV4 mRNA
      expression is up-regulated in patients with inflammatory bowel diseases (IBD).
      Furthermore, selective blockade of TRPV4 in the 2,4,6-trinitrobenzenesulfonic
      acid animal model alleviates colitis and pain associated with the intestinal
      inflammation. Our study indicates that TRPV4 may play a role in mechanisms of
      defense in intestinal inflammation and that TRPV4 may be an attractive target for
      future systemic or topic anti-inflammatory treatment in patients with IBD.

PMID- 22882779
TI  - Cigarette smoking and the risk of venous thromboembolism: the Tromso Study.
AB  - BACKGROUND: Conflicting findings have been reported on the association between
      smoking and the risk of venous thromboembolism (VTE). OBJECTIVES: To conduct a
      prospective, population-based cohort study to investigate the association between
      cigarette smoking and the risk of incident VTE. PATIENTS/METHODS: Information on
      smoking habits was assessed by self-administered questionnaires in 24 576
      subjects, aged 25-96 years, participating in the fourth Tromso Study in 1994
      1995. Incident cases of VTE were registered until the end of follow-up at 1
      September 2007. RESULTS: A total of 389 incident VTE events (1.61 per 1000 person
      years) were registered during follow-up (median of 12.5 years). Heavy smokers (>
      20 pack-years) had a hazard ratio (HR) of 1.46 (95% confidence interval [CI] 1.04
      2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14-2.69) for provoked VTE,
      as compared with never smokers. The risk of provoked VTE increased with more pack
      years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked
      VTE. The number of pack-years was associated with increased risk of cancer and
      myocardial infarction, whereas the association between pack-years of smoking and
      VTE disappeared when failure times were censored at the occurrence of cancer or
      myocardial infarction. CONCLUSIONS: Heavy smoking was apparently a risk factor
      for provoked VTE in analyses with VTE events as the only outcome. The lack of
      association between smoking and risk of VTE in analyses censored at the
      occurrence of cancer or myocardial infarction may suggest that smoking
      attributable diseases or other predisposing factors are essential for smoking to
      convey a risk of VTE.

PMID- 22882780
TI  - Systematic review of methodology used in ultrasound studies aimed at creating
      charts of fetal size.
AB  - BACKGROUND: Reliable ultrasound charts are necessary for the prenatal assessment
      of fetal size, yet there is a wide variation of methodologies for the creation of
      such charts. OBJECTIVE: To evaluate the methodological quality of studies of
      fetal biometry using a set of predefined quality criteria of study design,
      statistical analysis and reporting methods. SEARCH STRATEGY: Electronic searches
      in MEDLINE, EMBASE and CINAHL, and references of retrieved articles. SELECTION
      CRITERIA: Observational studies whose primary aim was to create ultrasound size
      charts for bi-parietal diameter, head circumference, abdominal circumference and
      femur length in fetuses from singleton pregnancies. DATA COLLECTION AND ANALYSIS:
      Studies were scored against a predefined set of independently agreed
      methodological criteria and an overall quality score was given to each study.
      Multiple regression analysis between quality scores and study characteristics was
      performed. MAIN RESULTS: Eighty-three studies met the inclusion criteria. The
      highest potential for bias was noted in the following fields:
      'Inclusion/exclusion criteria', as none of the studies defined a rigorous set of
      antenatal or fetal conditions which should be excluded from analysis; 'Ultrasound
      quality control measures', as no study demonstrated a comprehensive quality
      assurance strategy; and 'Sample size calculation', which was apparent in six
      studies only. On multiple regression analysis, there was a positive correlation
      between quality scores and year of publication: quality has improved with time,
      yet considerable heterogeneity in study methodology is still observed today.
      CONCLUSIONS: There is considerable methodological heterogeneity in studies of
      fetal biometry. Standardisation of methodologies is necessary in order to make
      correct interpretations and comparisons between different charts. A checklist of
      recommended methodologies is proposed.

PMID- 22882782
TI  - The physics of epidemiology.

PMID- 22882781
TI  - Risk factors for community-acquired urinary tract infection caused by ESBL
      producing bacteria in children.
AB  - BACKGROUND: The aim of the present study was to investigate the risk factors of
      antimicrobial resistance in children with urinary tract infection caused by
      extended-spectrum beta-lactamase (ESBL)-producing bacteria. METHODS: A total of
      344 patients diagnosed with urinary tract infection (UTI) between January 2008
      and December 2009 were enrolled in this retrospective study. Causative
      microorganisms were ESBL-producing bacteria in 148 patients and non-ESBL
      producing bacteria in 196 patients. There was no difference between the two
      groups regarding distribution of age, sex and length of follow up. RESULTS: The
      most frequent causative agent was Escherichia coli, of which 41.4% were ESBL
      producing. Among Klebsiella species, 53.2% were ESBL producing. The proportion of
      ESBL-producing bacteria that were resistant to antibiotics was 83.1% for
      trimethoprim/sulfamethoxazole, 18.2% for nitrofurantoin, 47.3% for quinolones,
      and 39.9% for aminoglycosides. For non-ESBL-producing bacteria, the resistance
      rate was 62.2% for trimethoprim/sulfamethoxazole, 4.6% for nitrofurantoin, 9.7%
      for quinolones, and 9.7% for aminoglycosides. Age <1 year, high UTI recurrence
      rate, long duration of prophylaxis, use of cephalosporins for prophylaxis,
      hospitalization within the previous 3 months and clean intermittent
      catheterization were found to be significant risk factors for ESBL-producing
      bacteria (P < 0.05). Logistic regression analysis identified age <1 year and high
      recurrence UTI rate to be independent risk factors, increasing the risk 1.74-fold
      and 2.25-fold, respectively. CONCLUSIONS: Recognition of the risk factors for
      ESBL-producing bacteria may be helpful to determine new policies in the
      management of UTI. Recurrence of UTI should be prevented especially in the first
      year of life, and prophylactic cephalosporins should be avoided.

PMID- 22882783
TI  - The role of care-seeking delays in intrauterine fetal deaths among 'near-miss'
      women in Herat, Afghanistan.
AB  - BACKGROUND: Many pregnant women in resource-poor countries seek care only after
      developing severe complications during childbirth at home and often reach health
      facilities in moribund conditions. The objectives were to (i) investigate the
      association between care-seeking duration and fetal survival at admission; and
      (ii) assess the significance of care-seeking duration in relation to other
      determinants. METHODS: Data were analysed for 266 women who were pregnant with a
      singleton and admitted in life-threatening conditions to the maternity ward of
      Herat Regional Hospital in Afghanistan from February 2007 to January 2008.
      Information about the women's care-seeking durations, social and financial
      resources, reproductive factors, household economic status and household types
      were collected during interviews with the women and their husbands. Information
      about fetal heartbeats at admission was extracted from the women's medical
      records. RESULTS: Fifty-four per cent of the women had a decision delay lasting 3
      h or more; 69% had a transport delay lasting 3 h or more. Multivariable logistic
      regression analyses suggest that a decision delay lasting an hour or more
      increased the odds of fetal death by 6.6 (95% confidence interval [CI] 1.6, 26.3)
      compared with a delay less than 1 h. A woman's lack of financial autonomy and a
      distance from her natal home increased the odds of fetal death by 3.1 [95% CI
      1.1, 8.4] and 2.5 [95% CI 1.0, 6.3] respectively. CONCLUSION: An integrated
      approach to improving fetal and maternal health from pre-pregnancy through
      childbirth (including increasing women's social and financial resources) is
      crucial particularly where senior family members act as gatekeepers to women's
      access to health care.

PMID- 22882784
TI  - In-hospital neonatal mortality and the role of consanguinity.
AB  - BACKGROUND: Consanguinity which increases the risk of genetic disorders has been
      implicated at times in infant mortality. The aim of this study was to determine
      the association between consanguinity and in-hospital mortality in newborns.
      METHODS: Data was collected prospectively on all births from 26 hospitals in
      Lebanon from January 2004 to December 2008 and admitted to the National
      Collaborative Perinatal Neonatal Network. Secondary analysis was done on 65,402
      singletons, after exclusion of stillbirths, infants of multiple gestation and
      infants of second cousin progeny. RESULTS: In-hospital mortality was 6.7 per 1000
      live births (439/65,402). The rate of first cousin marriage was 9.9%.
      Consanguinity was significantly associated with in-hospital mortality (odds ratio
      2.4; 95% confidence interval (CI): 1.8, 3.1); consanguinity remained a
      significant predictor of mortality (odds ratio 1.8 [95% CI: 1.2, 2.9]) after
      adjusting for maternal age and education, crowding index, history of abortion,
      prenatal care, mode of delivery, gender, birthweight and apgar score at 5
      minutes. CONCLUSIONS: This association of consanguinity with in-hospital
      mortality points to potential genetic factors leading to this increased risk.
      Designing public health interventions, including raising the awareness and taking
      into consideration such risks in neonatal mortality studies are indicated.

PMID- 22882785
TI  - Social determinants of infant mortality in a historical Swedish cohort.
AB  - BACKGROUND: Infant mortality rates have fallen considerably in the past decades.
      However, because of sparseness of historical data, it is unclear how social
      differences in infant mortality have changed over time. METHODS: The aim of this
      study was to assess the association between prenatal social determinants and
      infant mortality in a Swedish cohort of 13,741 singletons born between 1915 and
      1929. Associations and potential mediation of these determinants through other
      maternal and birth factors were studied using Cox regression. Analyses were
      repeated for deaths within the neonatal and post-neonatal periods. RESULTS:
      Mother's single marital status, high parity, low birthweight (LBW), low
      gestational age and male sex were associated with infant mortality in fully
      adjusted models, whereas the associations of maternal social class, region of
      residence and maternal age appeared to be largely mediated through other
      variables. Contrary to studies reporting a 'LBW paradox', no interactions between
      gestational age or birthweight and maternal social characteristics on infant
      mortality were observed in this study. High maternal age, LBW and low/high
      gestational age were associated with neonatal mortality, whereas single marital
      status, high parity, LBW, low gestational age and male sex were associated with
      post-neonatal mortality. An association of family social class with post-neonatal
      mortality was largely mediated by other maternal variables. CONCLUSIONS: Our
      findings of determinants of neonatal and post-neonatal mortality in 1915-1929 are
      strikingly consistent with results from contemporary cohorts. On the other hand,
      contrary to most recent findings, there is no evidence of a LBW paradox in this
      historical cohort.

PMID- 22882786
TI  - Validity of using ICD-9-CM codes to identify selected categories of obstetric
      complications, procedures and co-morbidities.
AB  - BACKGROUND: The ability to measure and track changes in risk-adjusted obstetric
      complication rates using administrative data underpins efforts to improve
      obstetric quality of care, but the validity of this approach has not been
      adequately evaluated. We sought to assess the validity of using composites of ICD
      9-CM codes to identify selected categories obstetric complications and risk
      factors associated with complications. METHODS: Patients with ICD-9-CM codes for
      obstetric trauma/laceration, infection, haemorrhage, episiotomy or obesity
      discharged between January 2009 and March 2010 were identified in the study
      hospital's administrative data. One hundred medical records with ICD-9-CM codes
      of interest were randomly selected for review from each of the five categories.
      An additional 60 medical records without the ICD-9-CM codes of interest served as
      controls for each category. Sensitivity and specificity for the selected
      categories was estimated using inverse proportional weighting to adjust for
      sampling based on presence of one of the ICD-9-CM codes of interest. RESULTS:
      Weighted sensitivities ranged from 0.15 [95% CI 0.11, 0.20] for obesity to 1.00
      for overall infection while specificities ranged from 0.994 [95% CI 0.987, 0.998]
      for obesity to 0.999 [95% CI 0.996, 1.000] for episiotomy. Obese patients were
      not reliably identified and it was not possible ascertain whether some diagnoses
      were present on admission. CONCLUSIONS: For selected categories of obstetric
      complication diagnoses, use of composite sets of ICD-9-CM codes may be a valid
      method to identify patients within these complication categories.

PMID- 22882787
TI  - Risk models for benchmarking severe perineal tears during vaginal childbirth: a
      cross-sectional study of public hospitals in South Australia, 2002-08.
AB  - BACKGROUND: The incidence of third- and fourth-degree perineal tears during
      vaginal childbirth is being increasingly used as an indicator of the safety and
      quality of maternity health care services. In order to make fair comparisons
      across hospitals it may be necessary to estimate a probability of severe perineal
      tears for every woman, taking into account her risk profile. METHODS: Logistic
      regression analysis was used to estimate the probabilities of third- and fourth
      degree tears (n = 1582; 2.4%) in 65 598 vaginal births in publicly funded
      hospitals in South Australia, 2002-08. RESULTS: Maternal age >=25 years,
      primiparity, instrument assistance, Asian or African ethnicity, shoulder dystocia
      and increasing birthweight were all identified as factors that are associated
      with an increased risk of perineal tears. In parous women, episiotomy, with or
      without instrument assistance, was associated with more tears; but among
      nulliparous women, episiotomy was associated with significantly fewer tears when
      forceps assistance was required, and showed little or no association with tearing
      in vacuum-assisted or unassisted (spontaneous) births. CONCLUSION: The
      probabilities of severe perineal tears in first-time mothers giving birth to a
      term singleton with cephalic presentation, may range from under 1% to over 40%,
      according to a minimalist model containing only predictors unrelated to clinical
      management. If instrument assistance and episiotomy are also incorporated into
      the modelling, the estimated probability of tearing may exceed 50% in high risk
      individuals. Such variation highlights the need for risk adjustment when
      comparing hospitals with respect to their incidence of third or fourth degree
      perineal tears.

PMID- 22882788
TI  - Physical activity in the prevention of childhood obesity.
AB  - The current high prevalence of childhood obesity and its co-morbidities is
      concomitant with a low level of physical activity and an abundance of sedentary
      pastimes for Westernised children. To increase the participation of a majority of
      children in a sustained physical activity, interventions require a fair
      understanding and consideration of the influences of this behaviour, especially
      as children are overweight or obese. Basically, the physical activity behaviour
      of children depends on biological, sociocultural and psychosocial factors and
      their interplay. The recent literature lends support to the fact that some
      psychosocial factors such as self-efficacy and physical competence may be solid
      anchor points upon which to improve the participation of overweight and obese
      children in free-living physical activity. Thus, interventionists should first
      concentrate on improving these personal dimensions around which physiological and
      environmental factors might revolve. The development of motor skills may be a
      good means for enhancing the self-image of obese children.

PMID- 22882789
TI  - Low digit ratio predicts early age at menarche in Colombian schoolgirls.
AB  - BACKGROUND: The ratio between the lengths of the second and fourth fingers (digit
      ratio: 2D : 4D), a purported negative correlate of prenatal androgen exposure,
      has been inversely related to age at menarche. However, a recent study found high
      digit ratios in carriers of a single variant in the LIN28B gene, which has been
      linked to delayed menarche. METHODS: We investigated the association of digit
      ratio and age at menarche in 299 pre-menarcheal girls aged 5-12 years who
      participated in a longitudinal cohort study in Bogota, Colombia. Finger lengths
      were measured at baseline and the occurrence of menarche was periodically
      ascertained over a median 32 months of follow-up. We used time-to-event analysis
      to estimate median ages at menarche as well as hazard ratios for menarche
      according to tertiles of the digit ratio for each hand. RESULTS: Estimated median
      age at menarche was lower for girls in the lowest digit ratio tertile of the
      right hand compared with those in the highest (12.0 vs. 12.3 years; P-value =
      0.04). After adjustment for baseline age, height- and body mass index-for-age z
      scores, the hazard of menarche was 86% higher in girls of the lowest digit ratio
      tertile (hazard ratio 1.9 [95% confidence interval 1.2, 2.9]) compared with those
      in the highest digit ratio tertile of the right hand. No significant associations
      were found with the left hand. CONCLUSIONS: Digit ratio was positively associated
      with age at menarche in this longitudinal investigation, consistent with results
      from a recent gene-linkage study.

PMID- 22882790
TI  - The SELMA study: a birth cohort study in Sweden following more than 2000 mother
      child pairs.
AB  - BACKGROUND:  This paper describes the background, aim and study design for the
      Swedish SELMA study that aimed to investigate the importance of early life
      exposure during pregnancy and infancy to environmental factors with a major focus
      on endocrine disrupting chemicals for multiple chronic diseases/disorders in
      offspring. METHODS: The cohort was established by recruiting women in the 10th
      week of pregnancy. Blood and urine from the pregnant women and the child and air
      and dust from home environment from pregnancy and infancy period have been
      collected. Questionnaires were used to collect information on life styles, socio
      economic status, living conditions, diet and medical history. RESULTS: Of the
      8394 reported pregnant women, 6658 were invited to participate in the study.
      Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non
      participants, 2091 women were invited to a non-respondent questionnaire in order
      to examine possible selection bias. We found a self-selection bias in the
      established cohort when compared with the non-participant group, e.g.
      participating families did smoke less (14% vs. 19%), had more frequent asthma and
      allergy symptoms in the family (58% vs. 38%), as well as higher education among
      the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs.
      60%). CONCLUSIONS: These findings indicate that the participating families do not
      fully represent the study population and thus, the exposure in this population.
      However, there is no obvious reason that this selection bias will have an impact
      on identification of environmental risk factors.

PMID- 22882791
TI  - Using mixture models with linear predictors to identify incorrect gestational age
      in state birth records.
AB  - BACKGROUND: Birthweight distributions for early last-menstrual-period-based
      gestational ages are bimodal, and some birthweights in the right-side
      distribution are implausible for the specified gestational age. Mixture models
      can be used to identify births in the right-side distribution. The objective of
      this study was to determine which maternal and infant factors to include in the
      mixture models to obtain the best fitting models for New Jersey state birth
      records. METHODS: We included covariates in the models as linear predictors of
      the means of the component distributions and the proportion of births in each
      component. This allowed both the means and the proportions to vary across levels
      of the covariates. RESULTS: The final model included maternal age and timing of
      entry into prenatal care. The proportion of births in the right-side distribution
      was lowest for older mothers who entered prenatal care early, higher for teen
      mothers who entered prenatal care early, higher still for older mothers who
      entered prenatal care late, and highest for teens who entered prenatal care late.
      Over 44% of births were classified as incorrect reported gestational age.
      CONCLUSION: These results suggest that (1) including these two covariates as
      linear predictors of the means and mixing proportions gives the best model for
      identifying births with incorrect reported gestational age, (2) late entry into
      prenatal care is a mechanism by which erroneously short last-menstrual-period
      based gestational ages are generated, and (3) including linear predictors of the
      mixing proportions in the model increases the validity of the classification of
      incorrect reported gestational age.

PMID- 22882793
TI  - Disassociation of the SV40 genome from capsid proteins prior to nuclear entry.
AB  - BACKGROUND: Previously, we demonstrated that input SV40 particles undergo a
      partial disassembly in the endoplasmic reticulum, which exposes internal capsid
      proteins VP2 and VP3 to immunostaining. Then, in the cytoplasm, disassembly
      progresses further to also make the genomic DNA accessible to immune detection,
      as well as to detection by an ethynyl-2-deoxyuridine (EdU)-based chemical
      reaction. The cytoplasmic partially disassembled SV40 particles retain some of
      the SV40 capsid proteins, VP1, VP2, and VP3, in addition to the viral genome.
      FINDINGS: In the current study, we asked where in the cell the SV40 genome might
      disassociate from capsid components. We observed partially disassembled input
      SV40 particles around the nucleus and, beginning at 12 hours post-infection, 5
      Bromo-2-deoxyuridine (BrdU)-labeled parental SV40 DNA in the nucleus, as detected
      using anti-BrdU antibodies. However, among the more than 1500 cells examined, we
      never detected input VP2/VP3 in the nucleus. Upon translocation of the BrdU
      labeled SV40 genomes into nuclei, they were transcribed and, thus, are
      representative of productive infection. CONCLUSIONS: Our findings imply that the
      SV40 genome disassociates from the capsid proteins before or at the point of
      entry into the nucleus, and then enters the nucleus devoid of VP2/3.

PMID- 22882792
TI  - Review of self-reported physical activity assessments for pregnancy: summary of
      the evidence for validity and reliability.
AB  - BACKGROUND: Epidemiological studies and surveillance systems of pregnant women
      often rely on collection of physical activity through self-report. This
      systematic review identified and summarised self-reported physical activity
      assessments with evidence for validity and reliability among pregnant women.
      METHODS: Peer-reviewed articles published through 2011 were included if they
      assessed validity and/or reliability of an interviewer- or self-administered
      physical activity questionnaire or diary among pregnant women. RESULTS: We
      identified 15 studies, including 12 studies that assessed questionnaires and 4
      studies that assessed diaries, conducted in Australia, Finland, Norway, the U.K.,
      the U.S. and Vietnam. For questionnaires, 92% (11/12) assessed mode, all assessed
      frequency and/or duration and 58% (7/12) collected information on perceived
      intensity. All but one study (92%) assessed validity of the questionnaires.
      Questionnaires compared with objective measures (accelerometers, pedometers)
      ranged from slight to fair agreement, while comparison with other self-reported
      measures ranged from substantial to almost perfect agreement. Five studies (42%)
      assessed test-retest reliability of the questionnaires, ranging from substantial
      to almost perfect agreement. The four studies on diaries were all assessed for
      validity against objective measures, ranging from slight to substantial
      agreement. CONCLUSIONS: Selection of valid and reliable physical activity
      measures that collect information on dose (type, frequency, duration, intensity)
      is recommended to increase precision and accuracy in detecting associations of
      physical activity with maternal and fetal outcomes.

PMID- 22882794
TI  - Accuracy of HistoScanningTM for the prediction of a negative surgical margin in
      patients undergoing radical prostatectomy.
AB  - OBJECTIVE: To assess the accuracy of HistoScanningTM (HS) as a visualization tool
      for preoperative treatment planning for nerve-sparing (NS) radical prostatectomy
      (RP). PATIENTS AND METHODS: A retrospective study was carried out on 80 patients
      with prostate cancer undergoing RP from October 2009 to December 2009. All
      patients underwent a HS procedure 1 day before surgery. Frozen sections (FSs)
      were performed on each latero-posterior side of the prostate to assess for the
      presence of cancer. On the HS analysis, the region corresponding to that removed
      at FS was assessed for suspicious lesions. The size of suspicious lesions within
      this volume was compared with the FS histopathological analysis. RESULTS: HS
      results corresponded to a 93% probability of having a negative surgical margin in
      the FSs. The presence of a HS volume >=0.2 mL in a specific side was associated
      with a 3.7 times increased risk of a positive surgical margin at FS. CONCLUSIONS:
      HS has the potential to assist in the planning of NSRP. Larger, multicentre
      studies need to be performed for validation of these encouraging results.

PMID- 22882795
TI  - Acute Q fever in northern Queensland: variation in incidence related to rainfall
      and geographical location.
AB  - The aims of this study were to define the basic epidemiology of serologically
      confirmed acute Q fever in patients tested via the Townsville Hospital laboratory
      from 2000 to 2010 and to determine the impact of geographical location and
      seasonality on the incidence of acute cases in the Townsville region. Seven
      Statistical Local Areas (SLA) were identified as having an incidence higher than
      the average Queensland incidence over the study period. The SLA with the highest
      incidence was Woodstock-Ross with 24.9 cases/100,000. A clear seasonal peak was
      found, with the greatest number of cases observed in May, 3 months following the
      peak in rainfall in February. We hypothesize that an increase in wildlife numbers
      and drier conditions seen immediately following the wet season is the reason for
      the seasonal peak of human acute Q fever cases in Townsville.

PMID- 22882796
TI  - "Don't wait for them to come to you, you go to them". A qualitative study of
      recruitment approaches in community based walking programmes in the UK.
AB  - BACKGROUND: This study aimed to examine the experiences of walking promotion
      professionals on the range and effectiveness of recruitment strategies used
      within community based walking programmes within the United Kingdom. METHODS: Two
      researchers recruited and conducted semi-structured interviews with managers and
      project co-ordinators of community based walking programmes, across the UK, using
      a purposive sampling frame. Twenty eight interviews were conducted, with
      community projects targeting participants by age, physical activity status, socio
      demographic characteristics (i.e. ethnic group) or by health status. Three case
      studies were also conducted with programmes aiming to recruit priority groups and
      also demonstrating innovative recruitment methods. Data analysis adopted an
      approach using analytic induction. RESULTS: Two types of programmes were
      identified: those with explicit health aims and those without. Programme aims
      which required targeting of specific groups adopted more specific recruitment
      methods. The selection of recruitment method was dependent on the respondent's
      awareness of 'what works' and the resource capacity at their disposal. Word of
      mouth was perceived to be the most effective means of recruitment but using this
      approach took time and effort to build relationships with target groups, usually
      through a third party. Perceived effectiveness of recruitment was assessed by
      number of participants rather than numbers of the right participants. Some
      programmes, particularly those targeting younger adult participants, recruited
      using new social communication media. Where adopted, social marketing recruitment
      strategies tended to promote the 'social' rather than the 'health' benefits of
      walking. CONCLUSIONS: Effective walking programme recruitment seems to require
      trained, strategic, labour intensive, word-of-mouth communication, often in
      partnerships, in order to understand needs and develop trust and motivation
      within disengaged sedentary communities. Walking promotion professionals require
      better training and resources to deliver appropriate recruitment strategies to
      reach priority groups.

PMID- 22882797
TI  - Sex-specific outcomes of diabetic patients with acute myocardial infarction who
      have undergone percutaneous coronary intervention: a register linkage study.
AB  - BACKGROUND: The presence of diabetes mellitus poses a challenge in the treatment
      of patients with acute myocardial infarction (AMI). We aimed to evaluate the sex
      specific outcomes of diabetic and non-diabetic patients with AMI who have
      undergone percutaneous coronary intervention (PCI). METHODS: Data of the Estonian
      Myocardial Infarction Registry for years 2006-2009 were linked with the Health
      Insurance Fund database and the Population Registry. Hazard ratios (HRs) with the
      95% confidence intervals (CIs) for the primary composite outcome (non-fatal AMI,
      revascularization, or death whichever occurred first) and for the secondary
      outcome (all cause mortality) were calculated comparing diabetic with non
      diabetic patients by sex. RESULTS: In the final study population (n=1652), 14.6%
      of the men and 24.0% of the women had diabetes. Overall, the diabetics had higher
      rates of cardiovascular risk factors, co-morbidities, and 3-4 vessel disease
      among both men and women (p<0.01). Among women, the diabetic patients were
      younger, they presented later and less often with typical symptoms of chest pain
      than the non-diabetics (p<0.01). Women with diabetes received aspirin and
      reperfusion for ST-segment elevation AMI less often than those without diabetes
      (p<0.01). During a follow-up of over two years, in multivariate analysis,
      diabetes was associated with worse outcomes only in women: the adjusted HR for
      the primary outcome 1.44 (95% CI 1.05-1.96) and for the secondary outcome 1.83
      (95% CI 1.17-2.89). These results were largely driven by a high (12.0%) mortality
      during hospitalization of diabetic women. CONCLUSIONS: Diabetic women with AMI
      who have undergone PCI are a high-risk group warranting special attention in
      treatment strategies, especially during hospitalization. There is a need to
      improve the expertise to detect AMI earlier, decrease disparities in management,
      and find targeted PCI strategies with adjunctive antithrombotic regimes in women
      with diabetes.

PMID- 22882798
TI  - Bacterial adhesion to animal tissues: protein determinants for recognition of
      extracellular matrix components.
AB  - The extracellular matrix (ECM) is present within all animal tissues and organs.
      Actually, it surrounds the eukaryotic cells composing the four basic tissue
      types, i.e. epithelial, muscle, nerve and connective. ECM does not solely refer
      to connective tissue but composes all tissues where its composition, structure
      and organization vary from one tissue to another. Constituted of the four main
      fibrous proteins, i.e. collagen, fibronectin, laminin and elastin, ECM components
      form a highly structured and functional network via specific interactions. From
      the basement membrane to interstitial matrix, further heterogeneity exists in the
      organization of the ECM in various tissues and organs also depending on their
      physiological state. Back to a molecular level, bacterial proteins represent the
      most significant part of the microbial surface components recognizing adhesive
      matrix molecules (MSCRAMM). These cell surface proteins are secreted and
      localized differently in monoderm and diderm-LPS bacteria. While one collagen
      binding domain (CBD) and different fibronectin-binding domains (FBD1 to 8) have
      been registered in databases, much remains to be learned on specific binding to
      other ECM proteins via single or supramolecular protein structures. Besides
      theinteraction of bacterial proteins with individual ECM components, this review
      aims at stressing the importance of fully considering the ECM at supramolecular,
      cellular, tissue and organ levels. This conceptual view should not be overlooked
      to rigorously comprehend the physiology of bacterial interaction from commensal
      to pathogenic species.

PMID- 22882799
TI  - New insights on molecular mechanisms of renal aging.
AB  - Long-term transplant outcome is importantly influenced by the age of the organ
      donor. The mechanisms how age carries out its pathophysiological impact on graft
      survival are still not understood. One major contributing factor for the observed
      poor performance of old donor kidneys seems in particular the age-related loss in
      renal regenerative capacity. In this review, we will summarize recent findings
      about the molecular basis of renal aging with specific focus on the potential
      role of somatic cellular senescence and mitochondrial aging in renal transplant
      outcome.

PMID- 22882800
TI  - Direct detection of nasal Staphylococcus aureus carriage via helicase-dependent
      isothermal amplification and chip hybridization.
AB  - BACKGROUND: The bacterium Staphylococcus aureus constitutes one of the most
      important causes of nosocomial infections. One out of every three individuals
      naturally carries S. aureus in their anterior nares, and nasal carriage is
      associated with a significantly higher infection rate in hospital settings. Nasal
      carriage can be either persistent or intermittent, and it is the persistent
      carriers who, as a group, are at the highest risk of infection and who have the
      highest nasal S. aureus cell counts. Prophylactic decolonization of S. aureus
      from patients' noses is known to reduce the incidence of postsurgical infections,
      and there is a clear rationale for rapid identification of nasal S. aureus
      carriers among hospital patients. FINDINGS: A molecular diagnostic assay was
      developed which is based on helicase-dependent target amplification and amplicon
      detection by chip hybridization to a chip surface, producing a visible readout.
      Nasal swabs from 70 subjects were used to compare the molecular assay against
      culturing on "CHROMagar Staph aureus" agar plates. The overall relative
      sensitivity was 89%, and the relative specificity was 94%. The sensitivity rose
      to 100% when excluding low-count subjects (<100 S. aureus colony-forming units
      per swab). CONCLUSIONS: This molecular assay is much faster than direct culture
      and has sensitivity that is appropriate for identification of high-count (>100 S.
      aureus colony-forming units per swab) nasal S. aureus carriers who are at
      greatest risk for nosocomial infections.

PMID- 22882802
TI  - Dental trauma in patients with single mandibular fractures.
AB  - PURPOSE: The purposes of this study were to investigate the occurrence and
      patterns of dental trauma in patients with single mandibular fracture and to
      evaluate the relationships between dental injury and fracture site of mandible.
      MATERIALS AND METHODS: From January 2000 to December 2009, 869 patients with
      mandibular fractures were registered. Only the patients with single mandibular
      fracture were included. The information and data collected included age, gender,
      mechanism of injury, type of mandibular fracture, and type of dental injury.
      RESULTS: Single mandibular fractures were sustained in 294 (33.8%) patients. Of
      these, 43.5% (128 patients) presented with associated dental injuries (509
      injured teeth). The patients' male/female ratio was 2.46:1 (91 males and 37
      females). Patients in 30-39 year age group possessed the highest risk of
      suffering dental trauma (odds ratio = 2.004, P = 0.014). Road traffic accidents
      were the most common mechanism of injury (54, 42.2%). Lower-anterior teeth were
      more often injured in patients with symphysis fracture (P < 0.001), and patients
      with condylar fracture more frequently sustained upper-posterior teeth injury (P
      < 0.001). Lower-posterior teeth injury was mostly found in patients with
      mandibular body fracture (P < 0.001) or angle fracture (P < 0.001). Dental
      injuries were more prone to occur in patients who sustained only symphysis
      fractures (odds ratio = 3.283, P < 0.001), and the risk was only 0.193-fold in
      patients who sustained only mandible angle fractures (odds ratio = 0.193, P <
      0.001). CONCLUSIONS: The occurrence and type of dental injury were significantly
      related to the fracture site of mandible.

PMID- 22882803
TI  - Self-management education interventions for persons with schizophrenia: a meta
      analysis.
AB  - Although self-management education programs for persons with schizophrenia are
      being developed and advocated, uncertainty about their overall effectiveness
      remains. The purpose of this meta-analysis was to examine outcomes of self
      management education interventions in persons with schizophrenia. Six electronic
      databases were searched. Manual searches were conducted of the reference lists of
      the identified studies and major psychiatric journals. Randomized controlled
      trials of self-management education interventions aimed at reducing relapse and
      hospital readmissions, as well as improving symptoms, psychosocial functioning,
      and adherence to medication treatment were identified. Data were extracted and
      the quality of included studies were rated by two authors independently. Finally,
      13 studies with 1404 patients were included. Self-management education
      interventions were associated with a significant reduction of relapse events and
      re-hospitalizations. Patients who received self-management education were more
      likely to improve adherence to medication and symptoms compared to patients
      receiving other care. However, a benefit on psychosocial functioning was not
      confirmed in the current meta-analysis. The study concludes that self-management
      education intervention is a feasible and effective method for persons with
      schizophrenia and should be routinely offered to all persons with schizophrenia.

PMID- 22882801
TI  - Modulation of opioid receptor ligand affinity and efficacy using active and
      inactive state receptor models.
AB  - Mu opioid receptor (MOR) agonists are widely used for the treatment of pain;
      however, chronic use results in the development of tolerance and dependence. It
      has been demonstrated that coadministration of a MOR agonist with a delta opioid
      receptor (DOR) antagonist maintains the analgesia associated with MOR agonists,
      but with reduced negative side-effects. Using our newly refined opioid receptor
      models for structure-based ligand design, we have synthesized several
      pentapeptides with tailored affinity and efficacy profiles. In particular, we
      have obtained pentapeptides 8, Tyr-c(S-S)[DCys-1Nal-Nle-Cys]NH(2), and 12, Tyr
      c(S-S)[DCys-1Nal-Nle-Cys]OH, which demonstrates high affinity and full agonist
      behavior at MOR, high affinity but very low efficacy for DOR, and minimal
      affinity for the kappa opioid receptor (KOR). Functional properties of these
      peptides as MOR agonists/DOR antagonists lacking undesired KOR activity make them
      promising candidates for future in vivo studies of MOR/DOR interactions. Subtle
      structural variation of 12, by substituting D-Cys(5) for L-Cys(5), generated
      analog 13, which maintains low nanomolar MOR and DOR affinity, but which displays
      no efficacy at either receptor. These results demonstrate the power and utility
      of accurate receptor models for structure-based ligand design, as well as the
      profound sensitivity of ligand function on its structure.

PMID- 22882804
TI  - AF News: Editor: Shih-Ann Chen, M.D.*

PMID- 22882805
TI  - Randomized trial of the effectiveness of combined behavioral/pharmacological
      smoking cessation treatment in Syrian primary care clinics.
AB  - AIMS: Effectiveness of nicotine replacement therapy (NRT) for smoking cessation
      has not been evaluated in low income countries, such as Syria, where it is
      expensive and not widely available. We evaluated whether nicotine patch boosts
      smoking cessation rates when used in conjunction with behavioral support in
      primary care clinics in Aleppo, Syria. DESIGN: Two arm, parallel group,
      randomized, placebo controlled, double-blinded multi-site trial. SETTING: Four
      primary care clinics in Aleppo, Syria. PARTICIPANTS:  Two hundred and sixty-nine
      adult primary care patients received behavioral cessation counseling from a
      trained primary care physician and were randomized to receive six weeks of
      treatment with nicotine versus placebo patch. MEASUREMENTS: Primary end-points
      were prolonged abstinence (no smoking after a 2-week grace period) at end of
      treatment, and 6 and 12 months post-quit day, assessed by self-report and exhaled
      carbon monoxide levels of <10 p.p.m. FINDINGS: Treatment adherence was excellent
      and nicotine patch produced expected reductions in urges to smoke and withdrawal
      symptoms, but no treatment effect was observed. The proportion of patients in the
      nicotine and placebo groups with prolonged abstinence was 21.6% and 20.0%,
      respectively, at end of treatment, 13.4% and 14.1% at 6 months, and 12.7% and
      11.9% at 12 months. CONCLUSIONS:  Nicotine patches may not be effective in
      helping smokers in low-income countries to stop when given as an adjunct to
      behavioural support.

PMID- 22882806
TI  - Neural mechanisms underlying the facilitation of naming in aphasia using a
      semantic task: an fMRI study.
AB  - BACKGROUND: Previous attempts to investigate the effects of semantic tasks on
      picture naming in both healthy controls and people with aphasia have typically
      been confounded by inclusion of the phonological word form of the target item. As
      a result, it is difficult to isolate any facilitatory effects of a semantically
      focused task to either lexical-semantic or phonological processing. This
      functional magnetic resonance imaging (fMRI) study examined the neurological
      mechanisms underlying short-term (within minutes) and long-term (within days)
      facilitation of naming from a semantic task that did not include the phonological
      word form, in both participants with aphasia and age-matched controls. RESULTS:
      Behavioral results showed that a semantic task that did not include the
      phonological word form can successfully facilitate subsequent picture naming in
      both healthy controls and individuals with aphasia. The whole brain neuroimaging
      results for control participants identified a repetition enhancement effect in
      the short-term, with modulation of activity found in regions that have not
      traditionally been associated with semantic processing, such as the right lingual
      gyrus (extending to the precuneus) and the left inferior occipital gyrus
      (extending to the fusiform gyrus). In contrast, the participants with aphasia
      showed significant differences in activation over both the short- and the long
      term for facilitated items, predominantly within either left hemisphere regions
      linked to semantic processing or their right hemisphere homologues. CONCLUSIONS:
      For control participants in this study, the short-lived facilitation effects of a
      prior semantic task that did not include the phonological word form were
      primarily driven by object priming and episodic memory mechanisms. However,
      facilitation effects appeared to engage a predominantly semantic network in
      participants with aphasia over both the short- and the long-term. The findings of
      the present study also suggest that right hemisphere involvement may be
      supportive rather than maladaptive, and that a large distributed perisylvian
      network in both cerebral hemispheres supports the facilitation of naming in
      individuals with aphasia.

PMID- 22882807
TI  - Emotional loneliness is associated with mortality among mentally intact nursing
      home residents with and without cancer: a five-year follow-up study.
AB  - AIMS AND OBJECTIVES: Hypothesised that sociodemographic factors and illness
      variables would be associated with mortality and that emotional and social
      loneliness measured using the Social Provisions Scale would influence mortality
      among nursing homes residents with cancer. BACKGROUND: Studies are lacking on how
      emotional and social loneliness influence mortality among cognitively intact
      older people in nursing homes with and without a diagnosis of cancer. DESIGN: A
      cross-sectional design was used at baseline with a five-year follow-up of
      mortality. Methods.  A cohort of 227 cognitively intact (Clinical Dementia Rating
      scale score <=0.5) older residents (60 with cancer and 167 without) from 30
      nursing homes were followed from 2004-2005 to 2010. Data were collected by face
      to-face interview. Sociodemographic variables and medical diagnoses were obtained
      from the records. RESULTS: Survival did not differ significantly between
      residents with and without cancer. After adjustment for sociodemographic and
      illness variables, increasing age, higher education and comorbidity were
      associated with mortality. In the final model from a backward selection
      procedure, attachment (emotional loneliness) was associated with mortality.
      CONCLUSIONS: Independent of a cancer diagnosis or not, emotional loneliness, age,
      education and comorbidity influenced mortality among nursing homes residents
      without cognitive impairment. RELEVANCE TO CLINICAL PRACTICE: Nurses should pay
      attention to emotional loneliness among nursing homes residents independent of
      cancer and especially give attention to the importance to have a close confidant
      who provides emotional support.

PMID- 22882808
TI  - Co-producing social inclusion: the structure/agency conundrum.
AB  - There is a raft of policy guidelines indicating that mental health nurses should
      be increasing the social inclusion of mental health service users. Despite this
      there is no universally accepted definition of social inclusion and there is a
      dearth of empirical evidence on the successful outcome of increasing inclusion
      for mental health service users. Recognizing the lack of clarity surrounding the
      concept we have a produced a social inclusion framework to assist mental health
      professionals and service users to co-produce social inclusive outcomes. Although
      we agree that social inclusion can be a positive aspect of recovery, we question
      the extent to which mental health nurses and service users in co-production can
      overcome the social, economic and political structures that have created the
      social exclusion in the first place. An understanding and appreciation of the
      structure/agency conundrum is required if mental health nurses are to engage with
      service users in an attempt to co-produce socially inclusive outcomes.

PMID- 22882809
TI  - An informant questionnaire for detecting Alzheimer's disease: are some items
      better than others?
AB  - A decline in everyday cognitive functioning is important for diagnosing dementia.
      Informant questionnaires, such as the informant questionnaire on cognitive
      decline in the elderly (IQCODE), are used to measure this. Previously,
      conflicting results on the IQCODEs ability to discriminate between Alzheimer's
      disease (AD), mild cognitive impairment (MCI), and cognitively healthy elderly
      were found. We aim to investigate whether specific groups of items are more
      useful than others in discriminating between these patient groups. Informants of
      180 AD, 59 MCI, and 89 patients with subjective memory complaints (SMC) completed
      the IQCODE. To investigate the grouping of questionnaire items, we used a two
      dimensional graded response model (GRM).The association between IQCODE, age,
      gender, education, and diagnosis was modeled using structural equation modeling.
      The GRM with two groups of items fitted better than the unidimensional model.
      However, the high correlation between the dimensions (r=.90) suggested
      unidimensionality. The structural model showed that the IQCODE was able to
      differentiate between all patient groups. The IQCODE can be considered as
      unidimensional and as a useful addition to diagnostic screening in a memory
      clinic setting, as it was able to distinguish between AD, MCI, and SMC and was
      not influenced by gender or education.

PMID- 22882810
TI  - Good language-switchers are good task-switchers: evidence from Spanish-English
      and Mandarin-English bilinguals.
AB  - Bilingual advantages in executive control tasks are well documented, but it is
      not yet clear what degree or type of bilingualism leads to these advantages. To
      investigate this issue, we compared the performance of two bilingual groups and
      monolingual speakers in task-switching and language-switching paradigms. Spanish
      English bilinguals, who reported switching between languages frequently in daily
      life, exhibited smaller task-switching costs than monolinguals after controlling
      for between-group differences in speed and parent education level. By contrast,
      Mandarin-English bilinguals, who reported switching languages less frequently
      than Spanish-English bilinguals, did not exhibit a task-switching advantage
      relative to monolinguals. Comparing the two bilingual groups in language
      switching, Spanish-English bilinguals exhibited smaller costs than Mandarin
      English bilinguals, even after matching for fluency in the non-dominant language.
      These results demonstrate an explicit link between language-switching and
      bilingual advantages in task-switching, while also illustrating some limitations
      on bilingual advantages.

PMID- 22882811
TI  - Alternate but do not swim: a test for executive motor dysfunction in Parkinson
      disease.
AB  - The objective of this study is to learn if participants with Parkinson disease
      (PD), when compared to normal controls, are impaired in making simultaneous but
      independent right and left hand movements. Participants were tested with Luria's
      Alternating Hand Postures (AHP) test and modified AHP tests. Twelve PD
      participants without dementia and twelve matched controls were assessed for their
      ability to perform the parallel AHP test (both hands remaining in the same
      coronal plane) and with modifications of this test into swimming (alternative arm
      extension with finger extension and arm flexion with finger flexion) and reverse
      swimming (alternative arm extension-finger flexion and arm flexion-finger
      extension) movements. The participants with PD were significantly impaired when
      performing the parallel and the reverse swimming movements AHP tests, but not
      impaired on the swimming movements AHP test. Swimming movements may be
      phylogenetically and ontogenetically more primitive and not as heavily dependent
      on frontal-basal ganglia networks; thus performance of swimming movements during
      the parallel AHP test may decrease this test's sensitivity.

PMID- 22882812
TI  - Bimanual-vertical hand movements.
AB  - Patients often demonstrate attentional and action-intentional biases in both the
      transverse and coronal planes. In addition, when making forelimb movements in the
      transverse plane, normal participants also have spatial and magnitude
      asymmetries, but forelimb spatial asymmetries have not been studied in coronal
      space. Thus, to learn if when normal people make vertical movements they have
      right-left spatial and magnitude biases, seventeen healthy, blindfolded
      volunteers had their hands (holding pens) placed vertically in their midsagittal
      plane, 10 inches apart, on pieces of paper positioned above, below, and at eye
      level. Participants were asked to move their hands together vertically and meet
      in the middle. Participants demonstrated less angular deviation in the below-eye
      condition than in the other spatial conditions, when moving down than up, and
      with their right than left hand. Movements toward eye level from upper or lower
      space were also more accurate than movements in the other directions. Independent
      of hand, lines were longer with downward than upward movements and the right hand
      moved more distance than the left. These attentional-intentional asymmetries may
      be related to gravitational force, hand-hemispheric dominance, and spatial
      "where" asymmetries; however, the mechanisms accounting for these asymmetries
      must be ascertained by future research.

PMID- 22882813
TI  - Script generation of activities of daily living in HIV-associated neurocognitive
      disorders.
AB  - Script generation describes one's ability to produce complex, sequential action
      plans derived from mental representations of everyday activities. The aim of this
      study was to assess the effect of human immunodeficiency virus (HIV) infection on
      script generation performance. Sixty HIV+ individuals (48% of whom had HIV
      associated neurocognitive disorders [HAND]) and 26 demographically comparable HIV
      participants were administered a novel, standardized test of script generation,
      which required participants to verbally generate and organize the necessary steps
      for completing six daily activities. HAND participants evidenced significantly
      more total errors, intrusions, and script boundary errors compared to the HIV-
      sample, indicating difficulties inhibiting irrelevant actions and staying within
      the prescribed boundaries of scripts, but had adequate knowledge of the relevant
      actions required for each script. These findings are generally consistent with
      the executive dysfunction and slowing common in HAND and suggest that script
      generation may play a role in everyday functioning problems in HIV.

PMID- 22882814
TI  - Effort--what is it, how should it be measured?

PMID- 22882816
TI  - Introduction to the special issue: insights and applications from financial risk
      analysis.

PMID- 22882818
TI  - Colorimetric sensing of anions in water using ratiometric indicator-displacement
      assay.
AB  - The analysis of anions in water presents a difficult challenge due to their low
      charge-to-radius ratio, and the ability to discriminate among similar anions
      often remains problematic. The use of a 3*6 ratiometric indicator-displacement
      assay (RIDA) array for the colorimetric detection and identification of ten
      anions in water is reported. The sensor array consists of different combinations
      of colorimetric indicators and metal cations. The colorimetric indicators chelate
      with metal cations, forming the color changes. Upon the addition of anions,
      anions compete with the indicator ligands according to solubility product
      constants (K(sp)). The indicator-metal chelate compound changes color back
      dramatically when the competition of anions wins. The color changes of the RIDA
      array were used as a digital representation of the array response and analyzed
      with standard statistical methods, including principal component analysis and
      hierarchical clustering analysis. No confusion or errors in classification by
      hierarchical clustering analysis were observed in 44 trials. The limit of
      detection was calculated approximately, and most limits of detections of anions
      are well below MUM level using our RIDA array. The pH effect, temperature
      influence, interfering anions were also investigated, and the RIDA array shows
      the feasibility of real sample testing.

PMID- 22882819
TI  - Temporal gradients in microfluidic systems to probe cellular dynamics: a review.
AB  - Microfluidic devices have found a unique place in cellular studies due to the
      ease of fabrication, their ability to provide long-term culture, or the seamless
      integration of downstream measurements into the devices. The accurate and precise
      control of fluid flows also allows unique stimulant profiles to be applied to
      cells that have been difficult to perform with conventional devices. In this
      review, we describe and provide examples of microfluidic systems that have been
      used to generate temporal gradients of stimulants, such as waveforms or pulses,
      and how these profiles have been used to produce biological insights into
      mammalian cells that are not typically revealed under static concentration
      gradients. We also discuss the inherent analytical challenges associated with
      producing and maintaining temporal gradients in these devices.

PMID- 22882820
TI  - The hybrid experimental simplex algorithm--an alternative method for 'sweet spot'
      identification in early bioprocess development: case studies in ion exchange
      chromatography.
AB  - The capacity to locate efficiently a subset of experimental conditions necessary
      for the identification of an operating envelope is a key objective in many
      studies. We have shown previously how this can be performed by using the simplex
      algorithm and this paper now extends the approach by augmenting the established
      simplex method to form a novel hybrid experimental simplex algorithm (HESA) for
      identifying 'sweet spots' during scouting development studies. The paper
      describes the new algorithm and illustrates its use in two bioprocessing case
      studies conducted in a 96-well filter plate format. The first investigates the
      effect of pH and salt concentration on the binding of green fluorescent protein,
      isolated from Escherichia coli homogenate, to a weak anion exchange resin and the
      second examines the impact of salt concentration, pH and initial feed
      concentration upon the binding capacities of a FAb', isolated from E. coli
      lysate, to a strong cation exchange resin. Compared with the established
      algorithm, HESA was better at delivering valuable information regarding the size,
      shape and location of operating 'sweet spots' that could then be further
      investigated and optimized with follow up studies. To test how favorably these
      features of HESA compared with conventional DoE (design of experiments) methods,
      HESA results were also compared with approaches including response surface
      modeling experimental designs. The results show that HESA can return 'sweet
      spots' that are equivalently or better defined than those obtained from DoE
      approaches. At the same time the deployment of HESA to identify bioprocess
      relevant operating boundaries was accompanied by comparable experimental costs to
      those of DoE methods. HESA is therefore a viable and valuable alternative route
      for identifying 'sweet spots' during scouting studies in bioprocess development.

PMID- 22882821
TI  - Ag ion irradiated based sensor for the electrochemical determination of
      epinephrine and 5-hydroxytryptamine in human biological fluids.
AB  - A promising and highly sensitive voltammetric method has been developed for the
      first time for the determination of epinephrine (EP) and 5-hydroxytryptamine (5
      HT) using 120 MeV Ag ion irradiated multi-walled carbon nano tube (MWCNT) based
      sensor. The MWCNT were irradiated at various fluences of 1e12, 3e12 and 1e13 ions
      cm(-2) using palletron accelerator. The simultaneous determination of EP and 5-HT
      has been carried out in phosphate buffer solution of pH 7.20 using square wave
      voltammetry and cyclic voltammetry. Experimental results suggested that
      irradiation of MWCNT by Ag ions enhanced the electrocatalytic activity due to
      increase in effective surface area and insertion of Ag ions, leading to a
      remarkable enhancement in peak currents and shift of peak potentials to less
      positive values as compared to the unirradiated MWCNT (pristine). The developed
      sensor exhibited a linear relationship between peak current and concentration of
      EP and 5-HT in the range 0.1-105 MUM with detection limit (3sigma/b) of 2 nM and
      0.75 nM, respectively. The practical utility of irradiation based MWCNT sensor
      has been demonstrated for the determination of EP and 5-HT in human urine and
      blood samples.

PMID- 22882822
TI  - Analysis of large experimental datasets in electrochemical impedance
      spectroscopy.
AB  - An approach for the analysis of large experimental datasets in electrochemical
      impedance spectroscopy (EIS) has been developed. The approach uses the idea of
      successive Bayesian estimation and splits the multidimensional EIS datasets into
      parts with reduced dimensionality. Afterwards, estimation of the parameters of
      the EIS-models is performed successively, from one part to another, using complex
      nonlinear least squares (CNLS) method. The results obtained on the previous step
      are used as a priori values (in the Bayesian form) for the analysis of the next
      part. To provide high stability of the sequential CNLS minimisation procedure, a
      new hybrid algorithm has been developed. This algorithm fits the datasets of
      reduced dimensionality to the selected EIS models, provides high stability of the
      fitting and allows semi-automatic data analysis on a reasonable timescale. The
      hybrid algorithm consists of two stages in which different zero-order
      optimisation strategies are used, reducing both the computational time and the
      probability to overlook the global optimum. The performance of the developed
      approach has been evaluated using (i) simulated large EIS dataset which
      represents a possible output of a scanning electrochemical impedance microscopy
      experiments, and (ii) experimental dataset, where EIS spectra were acquired as a
      function of the electrode potential and time. The developed data analysis
      strategy showed promise and can be further extended to other electroanalytical
      EIS applications which require multidimensional data analysis.

PMID- 22882823
TI  - Streamlining sample preparation and gas chromatography-tandem mass spectrometry
      analysis of multiple pesticide residues in tea.
AB  - In this work, a new rapid method for the determination of 135 pesticide residues
      in green and black dry tea leaves and stalks employing gas chromatography coupled
      to tandem mass spectrometry (GC-MS/MS) with a triple quadrupole was developed and
      validated. A substantial simplification of sample processing prior to the
      quantification step was achieved: after addition of water to a homogenised
      sample, transfer of analytes into an acetonitrile layer was aided by the addition
      of inorganic salts. Bulk co-extracts, contained in the crude organic extract
      obtained by partition, were subsequently removed by liquid-liquid extraction
      using hexane with the assistance of added 20% (w/w) aqueous NaCl solution. The
      importance of matrix hydration prior to the extraction for achieving good
      recoveries was demonstrated on tea samples with incurred pesticide residues. For
      most of the analytes, recoveries in the acceptable range of 70-120% and
      repeatabilities (relative standard deviations, RSDs) <=20% were achieved for both
      matrices at spiking levels of 0.01, 0.1 and 1 mg kg(-1). Under optimised GC-MS/MS
      conditions, most of the analytes gave lowest calibration level <=0.01 mg kg(-1),
      permitting the control at the maximum residue levels (MRLs) laid down in
      Regulation (EC) No 396/2005. The developed method was successfully applied to the
      determination of pesticide residues in real tea samples.

PMID- 22882824
TI  - Improvement of solid phase microextraction fiber assembly and interface for
      liquid chromatography.
AB  - Modifications were made on commercial SPME fiber assembly and SPME-LC interface
      to improve the applicability of SPME for LC. Polyacrylonitrile (PAN)/C18 bonded
      fuse silica was used as the fiber coating for LC applications because the fiber
      coating was not swollen in common LC solvents at room temperature. The inner
      tubing of SPME fiber assembly was replaced with a 457 MUm outside diameter (o.d.)
      solid nitinol rod. And the coated fiber (o.d. 290 MUm) was installed onto the
      nitinol rod. The inner diameter (i.d.) of the through hole of the ferrule in the
      SPME-LC interface was enlarged to 508 MUm to accommodate the nitinol rod. The
      much larger inner rod protected the fiber coating from being stripped when the
      fiber was withdrawn from the SPME-LC interface. The system was evaluated in term
      of pressure test, desorption optimization, peak shape, carryovers, linear range,
      precision, and limit of detection (LOD) with polycyclic aromatic hydrocarbons
      (PAHs) as the test analytes. The results demonstrated that the improved system
      was robust and reliable. It overcame the drawbacks, such as leak of solvents and
      damage of fiber coatings, associated with current SPME fibers and SPME-LC
      interface. Another sealing mechanism was proposed by sealing the nitinol rod with
      a specially designed poly(ether ether ketone) (PEEK) fitting. The device was
      fabricated and tested for manual use.

PMID- 22882825
TI  - Hollow fiber based liquid-phase microextraction for the determination of mercury
      traces in water samples by electrothermal atomic absorption spectrometry.
AB  - A three-phase liquid microextraction procedure for the determination of mercury
      at low concentrations is discussed. To the aqueous sample placed at pH 7 by means
      of a phosphate buffer, 0.002% (m/v) 1-(2-pyridylazo)-2-naphthol (PAN) is
      incorporated, and the mixture submitted to microextraction with a hollow-fiber
      impregnated with toluene and whose lumen contains a 0.05 mol L(-1) ammonium
      iodide solution. The final measurement of the extract is carried out by
      electrothermal atomic absorption spectrometry (300 degrees C and 1100 degrees C
      for the calcination and atomization temperatures, respectively). The pyrolytic
      graphite atomizer is coated electrolytically with palladium. An enrichment factor
      of 270, which results in a 0.06 MUg L(-1) mercury for the detection limit is
      obtained. The relative standard deviation at the 1 MUg L(-1) mercury level is
      3.2% (n=5). The reliability of the procedure is verified by analyzing waters as
      well as six certified reference materials.

PMID- 22882826
TI  - Solid-phase microextraction using octadecyl-bonded silica immobilized on the
      surface of a rotating disk: determination of hexachlorobenzene in water.
AB  - Solid-phase microextraction of hexachlorobenzene from water was implemented for
      the first time on a rotating disk coated with an octadecyl-bonded silica (C(18))
      sorptive phase. The results indicate that the sorption performance of this phase
      for the model analyte selected is similar to that observed using a rotating disk
      containing PDMS. In both cases, equilibrium is achieved within approximately 120
      min for samples volumes of 50 mL and decreases to 20-30 min when the sample
      volume is decreased to 10 mL. The comparable behavior observed for the sorption
      of HCB in both phases is consistent with a similar rate-determining step for
      extraction, which suggests that the overall mass transfer of analyte is not
      limited by internal diffusion into the phase but by diffusion into the aqueous
      stagnant layer. The main advantage in the use of the C(18) phase is that the
      elution of the analyte was achieved in 15 min compared with 45 min for PDMS
      because, in the case of C(18), dichloromethane can be used as the eluting
      solvent. The detection limit of the method was 0.08 MUg L(-1) HCB for a tap-water
      sample. The mean recovery for the analyte was 84+/-2% and 85+/-3% for the C(18)
      and PDMS phases, respectively, which indicates good accuracy and precision of the
      method.

PMID- 22882827
TI  - Improve accuracy and sensibility in glycan structure prediction by matching
      glycan isotope abundance.
AB  - Mass Spectrometry (MS) is a powerful technique for the determination of glycan
      structures and is capable of providing qualitative and quantitative information.
      Recent development in computational method offers an opportunity to use glycan
      structure databases and de novo algorithms for extracting valuable information
      from MS or MS/MS data. However, detecting low-intensity peaks that are buried in
      noisy data sets is still a challenge and an algorithm for accurate prediction and
      annotation of glycan structures from MS data is highly desirable. The present
      study describes a novel algorithm for glycan structure prediction by matching
      glycan isotope abundance (mGIA), which takes isotope masses, abundances, and
      spacing into account. We constructed a comprehensive database containing 808
      glycan compositions and their corresponding isotope abundance. Unlike most
      previously reported methods, not only did we take into count the m/z values of
      the peaks but also their corresponding logarithmic Euclidean distance of the
      calculated and detected isotope vectors. Evaluation against a linear classifier,
      obtained by training mGIA algorithm with datasets of three different human tissue
      samples from Consortium for Functional Glycomics (CFG) in association with
      Support Vector Machine (SVM), was proposed to improve the accuracy of automatic
      glycan structure annotation. In addition, an effective data preprocessing
      procedure, including baseline subtraction, smoothing, peak centroiding and
      composition matching for extracting correct isotope profiles from MS data was
      incorporated. The algorithm was validated by analyzing the mouse kidney MS data
      from CFG, resulting in the identification of 6 more glycan compositions than the
      previous annotation and significant improvement of detection of weaker peaks
      compared with the algorithm previously reported.

PMID- 22882828
TI  - Utilization of metabolomics to identify serum biomarkers for hepatocellular
      carcinoma in patients with liver cirrhosis.
AB  - Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC)
      in patients with liver cirrhosis is believed to contribute towards early
      detection, treatment, and understanding of the molecular mechanisms of HCC. In
      this study, we compare metabolite levels in sera of 78 HCC cases with 184
      cirrhotic controls by using ultra performance liquid chromatography coupled with
      a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following
      data preprocessing, the most relevant ions in distinguishing HCC cases from
      patients with cirrhosis are selected by parametric and non-parametric statistical
      methods. Putative metabolite identifications for these ions are obtained through
      mass-based database search. Verification of the identities of selected
      metabolites is conducted by comparing their MS/MS fragmentation patterns and
      retention time with those from authentic compounds. Quantitation of these
      metabolites is performed in a subset of the serum samples (10 HCC and 10
      cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple
      quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass
      spectrometers. The results of this analysis confirm that metabolites involved in
      sphingolipid metabolism and phospholipid catabolism such as sphingosine-1
      phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in
      sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include
      those involved in bile acid biosynthesis (specifically cholesterol metabolism)
      such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid
      (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and
      taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC
      biomarker discovery utilizing metabolomics as an efficient and cost-effective
      platform. Our work shows that metabolomic profiling is a promising tool to
      identify candidate metabolic biomarkers for early detection of HCC cases in high
      risk population of cirrhotic patients.

PMID- 22882829
TI  - Assessment of benzophenone-4 reactivity with free chlorine by liquid
      chromatography quadrupole time-of-flight mass spectrometry.
AB  - The stability of the UV filter benzophenone-4 (BP-4) in free chlorine-containing
      water was investigated, for the first time, by liquid chromatography quadrupole
      time-of-flight mass spectrometry (LC-QqTOF-MS). High mass accuracy and resolution
      capabilities of this hybrid mass spectrometer were used for the reliable
      assignation of empirical formulae and chemical structures of BP-4 derivatives.
      Time-course profiles of the parent compound and its by-products were
      simultaneously recorded by direct injection of sample aliquots, after quenching
      the excess of chlorine, in the LC-QqTOF-MS system. At neutral pHs, in excess of
      chlorine, BP-4 showed a limited stability fitting a pseudo-first-order
      degradation kinetics. A noticeable reduction in the half-lives of BP-4 was
      observed when increasing the sample pH between 6 and 8 units and also in presence
      of bromide traces. The reaction pathway of this UV filter involved a first
      electrophilic substitution of hydrogen per chlorine (or bromide) in the phenolic
      ring, followed by oxidation of the carbonyl moiety to an ester group, which
      induced a further electrophilic substitution in the same aromatic ring. Above
      reactions were also noticed when mixing a BP-4 containing personal care product
      with chlorinated tap water and in chlorinated swimming pool and sewage water,
      previously spiked with a BP-4 standard.

PMID- 22882830
TI  - The measurement of organically complexed FeII in natural waters using competitive
      ligand reverse titration.
AB  - Whilst there is increasing evidence for the presence of stabilized Fe(II)
      associated with organic matter in aquatic environments, the absence of a reliable
      method for determining Fe(II) speciation in solution has inhibited the study of
      this aspect of Fe biogeochemistry. A technique is described here for the
      determination of Fe(II) organic complexation in natural waters that is based on
      competitive ligand reverse titration and a model fit to experimental results,
      from which ligand concentration and a conditional stability constant can be
      obtained. Spectrophotometry was used to detect the Ferrozine (FZ) complex with
      reactive Fe(II), which in combination with a liquid waveguide capillary cell
      (LWCC) enabled high sensitivity and precision measurements of Fe(II) to be made.
      A series of samples was collected in the Itchen River in Southampton, UK to test
      the method at a wide range of salinities including river water. Levels of Fe(II)
      and total dissolved Fe were within previously reported values for this system.
      Fe(II) was found to occur organically complexed with values for K'(Fe(II)L)
      (conditional stability constant for Fe(II)-natural ligand complexes) of ~8 at
      salinities between 0 and 21, whilst no measurable complexation was detected at a
      salinity of 31. This work demonstrates that spectrophotometry can be used in
      combination with ligand competition to investigate metal speciation in natural
      waters.

PMID- 22882831
TI  - Electrochemical immunosensor for rapid and sensitive determination of estradiol.
AB  - This work describes the preparation of an electrochemical immunosensor for
      estradiol based on the surface modification of a screen printed carbon electrode
      with grafted p-aminobenzoic acid followed by covalent binding of streptavidin
      (Strept) and immobilization of biotinylated anti-estradiol (anti-estradiol
      Biotin). The hormone determination was performed by applying a competitive
      immunoassay with peroxidase-labelled estradiol (HRP-estradiol) and measurement of
      the amperometric response at -200 mV using hydroquinone (HQ) as redox mediator.
      The calibration curve for estradiol exhibited a linear range between 1 and 250 pg
      mL(-1) (r=0.990) and a detection limit of 0.77 pg mL(-1) was achieved. Cross
      reactivity studies with other hormones related with estradiol at physiological
      concentration levels revealed the practical specificity of the developed method
      for estradiol. A good reproducibility, with RSD=5.9% (n=8) was also observed. The
      operating stability of a single bioelectrode modified with anti-estradiol-Biotin
      Strept was nine days when it was stored at 8 degrees C under humid conditions
      between measurements. The developed immunosensor was applied to the analysis of
      certified serum and spiked urine samples with good results.

PMID- 22882832
TI  - Spatially selective reagent delivery into cancer cells using a two-layer
      microfluidic culture system.
AB  - In this work, we demonstrate a two-layer microfluidic system capable of spatially
      selective delivery of drugs and other reagents under low shear stress. Loading
      occurs by hydrodynamically focusing a reagent stream over a particular region of
      the cell culture. The system consisted of a cell culture chamber and fluid flow
      channel, which were located in different layers to reduce shear stress on cells.
      Cells in the center of the culture chamber were exposed to parallel streams of
      laminar flow, which allowed fast changes to be made to the cellular environment.
      The shear force was reduced to 2.7 dyn cm(-2) in the two-layer device (vs. 6.0
      dyn cm(-2) in a one-layer device). Cells in the side of the culture chamber were
      exposed to the side streams of buffer; the shear force was further reduced to a
      greater extent since the sides of the culture chamber were separated from the
      main fluid path. The channel shape and flow rate of the multiple streams were
      optimized for spatially controlled reagent delivery. The boundaries between
      streams were well controlled at a flow rate of 0.1 mL h(-1), which was optimized
      for all streams. We demonstrated multi-reagent delivery to different regions of
      the same culture well, as well as selective treatment of cancer cells with a
      built in control group in the same well. In the case of apoptosis induction using
      staurosporine, 10% of cells remained viable after 24 h of exposure. Cells in the
      same chamber, but not exposed to staurosporine, had a viability of 90%. This chip
      allows dynamic observation of cellular behavior immediately after drug delivery,
      as well as long-term drug treatment with the benefit of large cell numbers,
      device simplicity, and low shear stress.

PMID- 22882833
TI  - A novel optical nanoprobe for trypsin detection and inhibitor screening based on
      Mn-doped ZnSe quantum dots.
AB  - In this paper, a novel optical nanoprobe (Mn:ZnSe d-dots-Arg(6)) for trypsin
      detection and its inhibitor screening has been constructed successfully based on
      the fluorescence quenching and recovery of Mn:ZnSe d-dots. Mn:ZnSe d-dots would
      aggregate in the presence of positively charged Arg(6) (six arginine residues)
      due to electrostatic interactions that result in the fluorescence quenching.
      Arg(6) can be hydrolyzed into small fragments in the presence of trypsin, and
      accordingly, the aggregation of Mn:ZnSe d-dots can be prohibited, which lead to
      the fluorescence recovery. Experimental results show that the recovery in
      fluorescence intensity is linearly proportional to the concentration of trypsin
      within the range of 0.1-12.0 MUg mL(-1) with a detection limit of 40 ng mL(-1)
      under the optimized experimental conditions. We also prove the feasibility of
      fluorescence recovery of Mn:ZnSe d-dots for trypsin detection through the
      resonance light scattering (RLS) technique. Additionally, the optical nanoprobe
      can be employed for screening the inhibitors of trypsin. The optical nanoprobe
      was successfully applied for the determination of trypsin in human serum and
      urine samples with good accuracy and satisfactory recovery.

PMID- 22882834
TI  - Preparation of magnetite/poly(styrene-divinylbenzene) nanoparticles for selective
      enrichment-determination of fenitrothion in environmental and biological samples.
AB  - In the present study, a cross-linked nano-sized spherical magnetic poly(styrene
      divinylbenzene) is synthesized and used as an adsorbent for enrichment
      determination of fenitrothion. A miniemulsion polymerization procedure was used
      to prepare the adsorbent. The magnetic adsorbent was characterized by FT-IR, SEM
      and TEM. The prepared magnetic adsorbent nanoparticles were mixed with magnetite
      nanoparticles for faster and more efficient magnetic precipitation. The reduced
      fenitrothion was coupled with 3-methyl-2-benzothiazolinone hydrazone and then the
      blue colored complex was extracted. The blue derivative of fenitrothion was
      eluted by a 1 mL aliquot of 1-propanol prior to spectrophotometry at 571 nm.
      Beer's law was obeyed in the range of 2-230 ng mL(-1) of fenitrothion with
      relative standard deviation and recovery in the ranges of 0.9-5.1% and 97.2
      100.0%, respectively. Selectivity of the method was evaluated, and the method was
      successfully applied to the determination of fenitrothion in various water, soil,
      urine and human plasma samples.

PMID- 22882835
TI  - Evaluation of imidazole-based compounds as heme oxygenase-1 inhibitors.
AB  - Imidazole-based compounds previously synthesized in our laboratory were selected
      and reconsidered as inhibitors of heme oxygenase-1 obtained from the microsomal
      fractions of rat spleens. Most of tested compounds were good inhibitors with
      IC(50) values in the low micromolar range. Compounds were also assayed on
      membrane-free full-length recombinant human heme oxygenase-1; all tested
      compounds were unable to interact with human heme oxygenase-1 at 100 MUm
      concentrations with the exception of compounds 11 and 13 that inhibited the
      enzyme of 54% and 20%, respectively. The binding of the most active compound 11
      with heme or heme-conjugated human heme oxygenase-1 was also examined by spectral
      analyses. When heme was not conjugated to human heme oxygenase-1, compound 11
      caused changes in the heme spectrum only at concentration 50-fold (100 MUm)
      higher than that required to inhibit rat heme oxygenase-1; when heme was
      conjugated to human heme oxygenase-1, compound 11 was able to form a heme
      compound 11 complex also at low micromolar concentrations. To obtain information
      on the binding mode of the tested compounds with enzyme, docking studies and
      pharmacophore analysis were performed. Template docking results were in agreement
      with experimental inhibition data and with a structure-based pharmacophoric
      model. These data may be exploitable to design new OH-1 inhibitors.

PMID- 22882836
TI  - Evaluation of a national universal coverage campaign of long-lasting insecticidal
      nets in a rural district in north-west Tanzania.
AB  - BACKGROUND: Insecticide-treated nets (ITN) are one of the most effective measures
      for preventing malaria. Mass distribution campaigns are being used to rapidly
      increase net coverage in at-risk populations. This study had two purposes: to
      evaluate the impact of a universal coverage campaign (UCC) of long-lasting
      insecticidal nets (LLINs) on LLIN ownership and usage, and to identify factors
      that may be associated with inadequate coverage. METHODS: In 2011 two cross
      sectional household surveys were conducted in 50 clusters in Muleba district,
      north-west Tanzania. Prior to the UCC 3,246 households were surveyed and 2,499
      afterwards. Data on bed net ownership and usage, demographics of household
      members and household characteristics including factors related to socio-economic
      status were gathered, using an adapted version of the standard Malaria Indicator
      Survey. Specific questions relating to the UCC process were asked. RESULTS: The
      proportion of households with at least one ITN increased from 62.6% (95%
      Confidence Interval (CI) = 60.9-64.2) before the UCC to 90.8% (95% CI = 89.0
      92.3) afterwards. ITN usage in all residents rose from 40.8% to 55.7%. After the
      UCC 58.4% (95% CI = 54.7-62.1) of households had sufficient ITNs to cover all
      their sleeping places. Households with children under five years (OR = 2.4, 95%
      CI = 1.9-2.9) and small households (OR = 1.9, 95% CI = 1.5-2.4) were most likely
      to reach universal coverage. Poverty was not associated with net coverage. Eighty
      percent of households surveyed received LLINs from the campaign. CONCLUSIONS: The
      UCC in Muleba district of Tanzania was equitable, greatly improving LLIN
      ownership and, more moderately, usage. However, the goal of universal coverage in
      terms of the adequate provision of nets was not achieved. Multiple, continuous
      delivery systems and education activities are required to maintain and improve
      bed net ownership and usage.

PMID- 22882837
TI  - Reversible association of tetraspanin with Trichomonas vaginalis flagella upon
      adherence to host cells.
AB  - The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a
      prevalent sexually transmitted infection. Here, we report the cellular analyses
      of T. vaginalis tetraspanin 6 (TvTSP6). This family of membrane proteins has been
      implicated in cell adhesion, migration and proliferation in vertebrates. We
      observed that TvTSP6 expression is upregulated upon contact with vaginal
      ectocervical cells (VECs) and that parasite strains that are highly adherent to
      VECs express higher levels of TvTSP6 mRNA relative to poorly adherent strains.
      TvTSP6 is localized predominantly on the flagella of parasites cultured in the
      absence of host cells; however, adherence of the parasite to VECs initially
      results in a redistribution of the protein to intracellular vesicles and the
      plasma membrane of the main body of the cell. We found that a 16-amino-acid C
      terminal intracellular tail of TvTSP6 is necessary and sufficient for flagellar
      localization and protein redistribution when the parasite is in contact with
      VECs. Additionally, deletion of the C-terminal tail reduced parasite migration
      through Matrigel, a mimic of the extracellular matrix. Together, our data support
      roles for TvTSP6 in parasite migration in the host and sensory reception during
      infection.

PMID- 22882839
TI  - Prevalence of oral trauma in Para-Pan American Games athletes.
AB  - The aim of this cross-sectional epidemiological survey was to assess the
      prevalence of oral trauma in athletes representing 25 countries competing at the
      most recent Para-Pan American Games (III PARAPAN) held in Rio de Janeiro, Brazil.
      The study was approved by the appropriate institutional review board. The
      examiners participated in standardization and calibration training sessions
      before the field phase began. Invitations were sent to >1200 participating
      athletes competing in eight sports and to the Medical Committee of the Para-Pan
      American Sports Organization before and during the III PARAPAN. A convenience
      sample of 120 athletes was recruited. After signing an informed consent, all
      athletes answered a questionnaire. Data were collected at the clinical
      examination and recorded in a specific trauma form. The mean age of the athletes
      was 32.5 years. Males comprised 79.2% of the sample; females 20.8%. The
      prevalence of oral trauma among the athletes was 47.5% (N = 57). However, only 15
      athletes reported that these traumatic injuries were sports-related. The sport
      with the highest prevalence of oral trauma was judo (75%); the least was
      volleyball with no reported traumatic injuries. The most common traumatic injury
      was enamel fracture (27.4%). The teeth most affected were the maxillary permanent
      central incisors (N = 19), followed by the maxillary premolars (N = 8). On the
      basis of the results of this study of oral trauma among athletes examined at the
      III PARAPAN, a recommendation for enhanced educational efforts and the use of
      properly fitted mouthguards to prevent traumatic injuries among high-performance
      athletes with disabilities seems warranted.

PMID- 22882838
TI  - Identification of a complex genetic network underlying Saccharomyces cerevisiae
      colony morphology.
AB  - When grown on solid substrates, different microorganisms often form colonies with
      very specific morphologies. Whereas the pioneers of microbiology often used
      colony morphology to discriminate between species and strains, the phenomenon has
      not received much attention recently. In this study, we use a genome-wide assay
      in the model yeast Saccharomyces cerevisiae to identify all genes that affect
      colony morphology. We show that several major signalling cascades, including the
      MAPK, TORC, SNF1 and RIM101 pathways play a role, indicating that morphological
      changes are a reaction to changing environments. Other genes that affect colony
      morphology are involved in protein sorting and epigenetic regulation.
      Interestingly, the screen reveals only few genes that are likely to play a direct
      role in establishing colony morphology, with one notable example being FLO11, a
      gene encoding a cell-surface adhesin that has already been implicated in colony
      morphology, biofilm formation, and invasive and pseudohyphal growth. Using a
      series of modified promoters for fine-tuning FLO11 expression, we confirm the
      central role of Flo11 and show that differences in FLO11 expression result in
      distinct colony morphologies. Together, our results provide a first comprehensive
      look at the complex genetic network that underlies the diversity in the
      morphologies of yeast colonies.

PMID- 22882841
TI  - June 2012.

PMID- 22882840
TI  - Effects of different forms of monocular deprivation on primary visual cortex
      maps.
AB  - Monocular deprivation (MD) by lid suture is one of the classic paradigms for the
      study of developmental plasticity in the cerebral cortex, and we have detailed
      knowledge of its anatomical and physiological consequences as well as underlying
      molecular and cellular mechanisms. However, the effects of other forms of
      manipulating visual input through one eye on the functional architecture of the
      primary visual cortex (V1) have not yet been examined directly. We compared MD by
      lid suture with the effects of daily monocular lens wear using either a frosted
      lens or a neutral density (ND) filter. We used optical imaging of intrinsic
      signals and visually evoked potentials (VEPs) to assess responses in V1 to
      monocular stimulation. We found that loss of stimulus contrast through monocular
      frosted lens wear resulted in marked takeover of cortical territory by the
      nondeprived eye (NDE) similar to that caused by classic MD, and in virtual
      absence of orientation-selective responses following stimulation of the deprived
      eye (DE). Furthermore, amplitudes of VEPs in response to gratings of a range of
      spatial frequencies were significantly reduced in the DE compared to the NDE. In
      contrast, differences in luminance between two eyes caused by an ND filter in
      front of one eye did not affect ocular dominance and orientation maps, and there
      was no significant difference in the amplitude of VEPs elicited through the two
      eyes. Our results are consistent with previous electrophysiological studies in
      demonstrating that binocular pattern information is necessary to maintain normal
      functional maps in both eyes, while reduced luminance in one eye has little
      effect on the overall functional architecture and visual responses in V1.

PMID- 22882842
TI  - Mitogen-activated protein kinase signal pathways play an important role in right
      ventricular hypertrophy of tetralogy of Fallot.
AB  - BACKGROUND: Tetralogy of Fallot (TOF) is the most common malformation of children
      with an incidence of approximately 10% of congenital heart disease patients.
      There can be a wide spectrum to the severity of the anatomic defects, which
      include ventricular septal defect, aortic override, right ventricular outflow
      tract obstruction, and right ventricular hypertrophy. We examined the
      relationship between right ventricular hypertrophy in patients with TOF and the
      gene expression of factors in the mitogen-activated protein kinase (MAPK) signal
      pathway. METHODS: To gain insight into the characteristic gene(s) involved in
      molecular mechanisms of right ventricular hypertrophy in TOF, differential mRNA
      and micro RNA expression profiles were assessed using expression-based micro
      array technology on right ventricular biopsies from young TOF patients who
      underwent primary correction and on normal heart tissue. We then analyzed the
      gene expression of the MAPK signal pathway using reverse transcription-polymerase
      chain reaction (RT-PCR) in normals and TOF patients. RESULTS: Using the micro RNA
      chip V3.0 and human whole genome oligonucleotide microarray V1.0 to detect the
      gene expression, we found 1068 genes showing altered expression of at least two
      fold in TOF patients compared to the normal hearts, and 47 micro RNAs that showed
      a significant difference of at least two-fold in TOF patients. We then analyzed
      these mRNAs and micro RNAs by target gene predicting software Microcosm Targets
      version 5.0, and determined those mRNA highly relevant to the right ventricular
      hypertrophy by RT-PCR method. There were obvious differences in the gene
      expression of factors in the MAPK signal pathway when using RT-PCR, which was
      consistent to the results of the cDNA microarray. CONCLUSION: The upregulation of
      genes in the MAPK signal pathway may be the key events that contribute to right
      ventricular hypertrophy and stunted angiogenesis in patients with TOF.

PMID- 22882843
TI  - Effect of high-dose rosuvastatin loading before percutaneous coronary
      intervention in female patients with non-ST-segment elevation acute coronary
      syndrome.
AB  - BACKGROUND: Early loading statin therapy before percutaneous coronary
      intervention (PCI) is associated with reduced mortality and periprocedural
      myocardial injury. The aim of this study was to study the effect of rosuvastatin
      loading therapy before PCI in female patients with non-ST-segment elevation acute
      coronary syndrome (NSTEACS). METHODS: Consecutive 117 female patients with
      NSTEACS were randomly assigned to either the group of rosuvastatin loading before
      PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2
      hours before procedure, the loading dose group, n = 59) or the no rosuvastatin
      treatment group before PCI (control group, n = 58). Periprocedural myocardial
      injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP),
      interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the
      incidence of major adverse cardiac events (MACE) 3 months and 6 months later were
      assessed. RESULTS: The incidence of periprocedural myocardial injury was higher
      in control group than loading dose group (CKMB: 10.17% vs. 25.86%, P = 0.027;
      Troponin I: 11.86% vs. 29.31%, P = 0.019). MACE occurred in 1.69% of patients in
      loading dose group and 12.07% of those in control group 3 months after procedure
      (P = 0.026), 3.39% vs. 17.24% at 6 months (P = 0.014). The levels of hs-CRP, IL
      1, IL-6, and TNF-a in serum were not significantly different between the two
      groups before PCI, but after PCI they were significantly higher in control group.
      CONCLUSIONS: High-dose rosuvastatin loading before PCI significantly reduced
      periprocedural myocardial injury and periprocedural inflammation cytokines
      release and improved 3-month and 6-month clinical outcomes in female patients
      with NSTEACS who underwent PCI.

PMID- 22882844
TI  - Sex-dependent association of phosphodiesterase 4D gene polymorphisms with
      ischemic stroke in Henan Han population.
AB  - BACKGROUND: Recent evidence has implicated the gene for phosphodiesterase 4D
      (PDE4D) as susceptibility gene for ischemic stroke (IS) in Icelandic population.
      However, there are few reports on the associations between PDE4D gene
      polymorphisms and IS in Chinese individuals. The present study aimed to
      investigate the possible association of genetic polymorphisms in PDE4D gene with
      IS in Henan Han population. METHODS: A total of 400 patients with IS and 400
      matched controls were examined using a case-control design. Two single nucleotide
      polymorphism (SNPs) (rs918592 and rs2910829) in PDE4D gene were genotyped by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to
      test the association between the genetic factors and IS. Genetic parameter and
      association studies were carried out with SPSS 16.0. RESULTS: Among the two SNPs
      tested, the rs918592 was significantly associated with IS (OR: 1.351, 95%CI:
      1.110 - 1.645), especially in male patients (OR: 1.427, 95%CI: 1.105 - 1.844).
      Haplotype analysis showed that A-T was associated with an increased risk of the
      IS (OR: 2.114, 95%CI: 2.005 - 2.230) while G-T was associated with decreased risk
      of IS (OR: 0.419, 95%CI: 0.302 - 0.583). Protecting effect of haplotype G-T was
      also significant in males (OR: 0.264, 95%CI: 0.162 - 0.431). CONCLUSIONS: The
      present study demonstrated a strong association of rs918592 with IS. Haplotype A
      T increased the risk of IS while haplotype G-T had a protective effect in Henan
      Han population. The association was sex-dependent with male patients showing
      stronger effect.

PMID- 22882845
TI  - Proton magnetic resonance spectroscopy in the evaluation of infiltration zone of
      cerebral alveolar echinococcosis.
AB  - BACKGROUND: Cerebral alveolar echinococcosis (CAE) grows infiltratively like a
      malignant tumor, causing great harm to the human body. It is possible to display
      mass lesions of CAE using various imaging systems, but regarding the infiltrating
      proliferation active regions, it is difficult to evaluate its actual range using
      conventional magnetic resonance imaging (cMRI). This research focused on proton
      magnetic resonance spectroscopy ((1)HMRS) techniques to find the mass and
      infiltration zone of CAE. We explored the marginal zone (MZ) of CAE nearly close
      to the actual infiltrating scope, to provide reliable images for clinical
      purposes, to overcome shortcomings of cMRI, to formulate beneficial clinical
      surgical plans and assess prognosis. METHODS: Between September 2005 and May
      2011, 15 patients who were suffering from CAE (36 effective lesions altogether)
      were examined by (1)HMRS at the first affiliated hospital of Xinjiang Medical
      University. Multi-voxel (1)HMRS was acquired with a 1.5T MRI scanner.
      Concentrations and the ratios of the metabolites of CAE were calculated.
      Furthermore, changes in the concentrations of the metabolites containing N-acetyl
      aspartic-acid (NAA), choline (Cho), creatine (Cr), lipids and lactate (Lip + Lac)
      and the ratios of Cho/Cr, NAA/Cr, (Lip + Lac) /Cr were compared in the
      substantial region, 0 - 10 mm MZ, and 11 - 20 mm MZ of the infiltration zone, as
      well as the corresponding contralateral part of the normal brain parenchyma area
      (control group). RESULTS: In this study, the ratios of Cho/Cr in the substantial
      region, 0 - 10 mm MZ of infiltration zone and the control group were 1.78 +/-
      0.70, 1.90 +/- 0.54, and 0.78 +/- 0.15, respectively; the ratios of NAA/Cr were
      1.60 +/- 0.20, 1.80 +/- 0.42, 2.24 +/- 0.86, respectively; the ratios of (Lip +
      Lac)/Cr were 25.69 +/- 13.84, 25.18 +/- 16.03, and 0.61 +/- 0.15, respectively.
      From the control group, 11 - 20 mm MZ to 0 - 10 mm MZ and the substantial region
      of CAE, the concentrations of the metabolites showed that NAA and Cho decreased
      gradually and markedly. But (Lip + Lac) increased gradually and markedly. The
      ratios of Cho/Cr and NAA/Cr, (Lip + Lac)/Cr were statistically significant (P <
      0.0083) between the substantial region and the control group, as well as between
      the 0 - 10 mm MZ and the control group. The ratios of Cho/Cr and NAA/Cr, (Lip +
      Lac)/Cr displayed no statistically significant differences (P > 0.0083) between
      the substantial region and the 0 - 10 mm MZ. CONCLUSIONS: There was a
      pathological spectrum surrounding the infiltration zone of CAE. Multi-voxel 1HMRS
      has great clinical value for discerning the main lesion and the infiltration zone
      of CAE.

PMID- 22882846
TI  - Mortality and morbidity of acute hypoxemic respiratory failure and acute
      respiratory distress syndrome in infants and young children.
AB  - BACKGROUND: Acute hypoxemic respiratory failure (AHRF) often develops acute
      respiratory distress syndrome (ARDS), and its incidence and mortalities in
      critically ill pediatric patients in China were 2% and 40% respectively. This
      study aimed at prospectively investigating incidence, causes, mortality and its
      risk factors, and any relationship to initial tidal volume (V(T)) levels of
      mechanical ventilation, in children L5 years of age with AHRF and ARDS. METHODS:
      In 12 consecutive months in 23 pediatric intensive care units (PICU), AHRF and
      ARDS were identified in those requiring > 12 hour intratracheal mechanical
      ventilation and followed up for 90 days or until death or discharge. ARDS was
      diagnosed according to the American-European Consensus definitions. The mortality
      and ventilation free days (VFD) were measured as the primary outcome, and major
      complications, initial disease severity, and burden were measured as the
      secondary outcome. RESULTS: In 13 491 PICU admissions, there were 439 AHRF, of
      which 345 (78.6%) developed ARDS, resulting in incidences of 3.3% and 2.6%, and
      corresponding mortalities of 30.3% and 32.8% respectively along with 8.2 and 6.7
      times of relative risk of death in those with pneumonia (62.9%) and sepsis
      (33.7%) as major underlying diseases respectively. No association was found in
      V(T) levels during the first 7 days with mortality, nor for V(T) at levels < 6, 6
      - 8, 8 - 10, and > 10 ml/kg in the first 3 days with mortality or length of VFD.
      By binary Logistic regression analyses, higher pediatric risk of mortality score
      III, higher initial oxygenation index, and age < 1 year were associated with
      higher mortality or shorter VFD in AHRF. CONCLUSIONS: The incidence and
      mortalities of AHRF and ARDS in children L5 years were similar to or lower than
      the previously reported rates (in age up to 15 years), associated with initial
      disease severity and other confounders, but causal relationship for the initial
      V(T) levels as the independent factor to the major outcome was not found.

PMID- 22882847
TI  - Comparison of four prognostic models and a new Logistic regression model to
      predict short-term prognosis of acute-on-chronic hepatitis B liver failure.
AB  - BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically
      severe disease associated with major life-threatening complications including
      hepatic encephalopathy and hepatorenal syndrome. The aim of this study was to
      evaluate the short-term prognostic predictability of the model for end-stage
      liver disease (MELD), MELD-based indices, and their dynamic changes in patients
      with ACLF-HBV, and to establish a new model for predicting the prognosis of ACLF
      HBV. METHODS: A total of 172 patients with ACLF-HBV who stayed in the hospital
      for more than 2 weeks were retrospectively recruited. The predictive accuracy of
      MELD, MELD-based indices, and their dynamic change (D) were compared using the
      area under the receiver operating characteristic curve method. The associations
      between mortality and patient characteristics were studied by univariate and
      multivariate analyses. RESULTS: The 3-month mortality was 43.6%. The largest
      concordance (c) statistic predicting 3-month mortality was the MELD score at the
      end of 2 weeks of admission (0.8), followed by the MELD: sodium ratio (MESO)
      (0.796) and integrated MELD (iMELD) (0.758) scores, DMELD (0.752), DMESO (0.729),
      and MELD plus sodium (MELD-Na) (0.728) scores. In multivariate Logistic
      regression analysis, the independent factors predicting prognosis were hepatic
      encephalopathy (OR = 3.466), serum creatinine, international normalized ratio
      (INR), and total bilirubin at the end of 2 weeks of admission (OR = 10.302,
      6.063, 5.208, respectively), and cholinesterase on admission (OR = 0.255). This
      regression model had a greater prognostic value (c = 0.85, 95%CI 0.791 - 0.909)
      compared to the MELD score at the end of 2 weeks of admission (Z = 4.9851, P =
      0.0256). CONCLUSIONS: MELD score at the end of 2 weeks of admission is a useful
      predictor for 3-month mortality in ACLF-HBV patients. Hepatic encephalopathy,
      serum creatinine, international normalized ratio, and total bilirubin at the end
      of 2 weeks of admission and cholinesterase on admission are independent
      predictors of 3-month mortality.

PMID- 22882848
TI  - Diagnostic value of endometrial thickness determined by transvaginal sonography
      in infertile women with endometrial polyps.
AB  - BACKGROUND: Endometrial polyps (EPs) occur in approximately 34.9% of infertile
      women. Transvaginal sonography (TVS) is a routine, non-invasive component of
      fertility evaluation. Most ultrasonographic studies of EPs have focused on
      abnormal uterine bleeding; few have assessed EPs in infertile women. Furthermore,
      no studies have explored endometrial thickness and its correlation with EPs in
      infertile women. This study aimed to assess transvaginal sonographic assessment
      of endometrial thickness and its value in diagnosis and prediction of EPs in
      infertile women. METHODS: A retrospective study on 314 infertile women was
      conducted from June to December 2010. After TVS, endometrial biopsies were
      obtained by hysteroscopy. Pathologically confirmed EPs were taken as the gold
      standard. RESULTS: Based on recognized criteria, TVS had a sensitivity of 37.04%,
      specificity of 98.71%, positive predictive value of 90.91%, negative predictive
      value of 81.85%, and accuracy of 82.80% for diagnosing EPs. Mean endometrial
      thickness was significantly different in patients with and without EPs (P =
      0.0001). In women in the mid and late-proliferative phase, the endometrial
      thickness was significantly greater in those with EPs than in those without them
      (P = 0.0001 and 0.024). Receiver operating characteristic analysis showed that
      endometrial thickness had a sensitivity of 85.2% and specificity of 38% in the
      diagnosis of EPs, the area under the curve being 0.64. In the mid-proliferative
      phase, sensitivity was up to 90.9%, the area under the curve being 0.70.
      CONCLUSIONS: TVS is poor at detecting EPs in infertile women; however,
      transvaginal sonographic measurement of endometrial thickness is helpful. It is
      suggested that the diagnostic value of TVS for EPs in infertile women could be
      improved by adding the measurement of endometrial thickness to the variables that
      are routinely assessed.

PMID- 22882849
TI  - Optimization of Bartonella henselae multilocus sequence typing scheme using
      single-nucleotide polymorphism analysis of SOLiD sequence data.
AB  - BACKGROUND: Multi-locus sequence typing (MLST) is widely used to explore the
      population structure of numerous bacterial pathogens. However, for genotypically
      restricted pathogens, the sensitivity of MLST is limited by a paucity of
      variation within selected loci. For Bartonella henselae (B. henselae), although
      the MLST scheme currently used has been proven useful in defining the overall
      population structure of the species, its reliability for the accurate delineation
      of closely-related sequence types, between which allelic variation is usually
      limited to, at most, one or two nucleotide polymorphisms. Exploitation of high
      throughput sequencing data allows a more informed selection of MLST loci and
      thus, potentially, a means of enhancing the sensitivity of the schemes they
      comprise. METHODS: We carried out SOLiD resequencing on 12 representative B.
      henselae isolates and explored these data using single nucleotide polymorphism
      (SNP) analysis. We determined the number and distribution of SNPs in the genes
      targeted by the established MLST scheme and modified the position of loci within
      these genes to capture as much genetic variation as possible. RESULTS: Using
      genome-wide SNP data, we found the distribution of SNPs within each open reading
      frame (ORF) of MLST loci, which were not represented by the established B.
      henselae MLST scheme. We then modified the position of loci in the MLST scheme to
      better reflect the polymorphism in the ORF as a whole. The use of amended loci in
      this scheme allowed previously indistinguishable ST1 strains to be
      differentiated. However, the diversity of B. henselae was still rare in China.
      CONCLUSIONS: Our study demonstrates the use of SNP analysis to facilitate the
      selection of MLST loci to augment the currently-described scheme for B. henselae.
      And the diversity among B. henselae strains in China is markedly less than that
      observed in B. henselae populations elsewhere in the world.

PMID- 22882850
TI  - Antimicrobial resistance and molecular epidemiological characteristics of
      clinical isolates of Staphylococcus aureus in Changsha area.
AB  - BACKGROUND: Increasing prevalence of Staphylococcus aureus (S. aureus),
      particularly methicillin-resistant S. aureus (MRSA) has been reported in China.
      In this study, we investigated the drug resistance characteristic, genetic
      background, and molecular epidemiological characteristic of S. aureus in
      Changsha. METHODS: Between January 2006 and December 2008, 293 clinical isolates
      of S. aureus were collected from 11 hospitals in Changsha and identified by the
      Vitek-2 system. All the isolates were verified as MRSA by PCR amplification of
      both femA and mecA genes. K-B disk method was used to test drug sensitivity of S.
      aureus to antibiotics. Pulsed-field gel electrophoresis (PFGE) was performed for
      genotypic and homologous analysis of 115 isolates randomly selected from the
      original 293 clinical S. aureus isolates. RESULTS: S. aureus was highly resistant
      to penicillin, ampicillin, erythromycin, and clindamycin with resistant rates of
      96.6%, 96.6%, 77.1%, and 67.2% respectively. All the isolates were susceptible to
      tecoplanin, vancomycin, and linezolid. MRSA accounted for 64.8% (190/293) of all
      the S. aureus strains. The 115 S. aureus isolates were clustered into 39 PFGE
      types by PFGE typing, with 13 predominant patterns (designated types A to M)
      accounting for 89 isolates. The most prevalent PFGE type was type A (n = 56,
      48.7%) and 100.0% of type A strains were MRSA. PFGE type A included 13 subtypes,
      and the most prevalent subtype was subtype A1 (46.4%, 26/56). Strains with PFGE
      type A were isolated from eight hospitals (8/11), and both subtypes A1 and A4
      strains were isolated in a university hospital. CONCLUSIONS: Clinical isolates of
      S. aureus in Changsha were resistant to multiple traditional antibiotics. There
      was an outbreak of PFGE type A MRSA in this area and the A1 subtype was the
      predominant epidemic clone. Dissemination of the same clone was an important
      reason for the wide spread of MRSA.

PMID- 22882851
TI  - Endothelial progenitor cell transplantation ameliorates elastin breakdown in a
      Kawasaki disease mouse model.
AB  - BACKGROUND: Coronary artery damage from Kawasaki disease (KD) is closely linked
      to the dysfunction of endothelial progenitor cells (EPCs). The aim of the present
      study was to evaluate the therapeutic effect of EPCs transplantation in KD model.
      METHODS: Lactobacillus casei cell wall extract (LCWE)-induced KD model in C57BL/6
      mice was established. The model mice were injected intravenously with bone marrow
      derived in vitro expanded EPCs. Histological evaluation, number of circulating
      EPCs and the function of bone marrow EPCs were examined at day 56. RESULTS:
      Inflammation was found around the coronary artery of the model mice after 14
      days, Elastin breakdown was observed after 56 days. CM-Dil labeled EPCs
      incorporated into vessel repairing foci was found. At day 56, the number of
      peripheral EPCs in the KD model group was lower than in EPCs transplanted and
      control group. The functional index of bone marrow EPCs from the KD model group
      decreased in proliferation, adhesion and migration. Increased number of
      circulating EPCs and improved function were observed on the EPCs transplanted
      group compared with model group. CONCLUSION: Exogenously administered EPCs, which
      represent a novel strategy could prevent the dysfunction of EPCs, accelerate the
      repair of coronary artery endothelium lesion and decrease the occurrence of
      aneurysm.

PMID- 22882852
TI  - Effects of partial portal vein arterialization on liver regeneration after
      hepatectomy in minipigs with obstructive jaundice.
AB  - BACKGROUND: Hilar cholangiocarcinoma is a malignant tumor that is difficult to
      cure. The aim of this study was to observe the effects of flow-controlled partial
      portal vein arterializations (PPVA) on liver regeneration after hepatectomy in
      minipigs with chronic obstructive jaundice. METHODS: Eight minipigs were made
      into chronic obstructive jaundice models. United semi-hepatectomy, which imitates
      extended radical surgery for treatment of hilar cholangiocarcinoma, was then
      performed. The eight minipigs were randomly divided into groups A and B (n = 4
      minipigs each). PPVA was performed in Group A but not in Group B. The effects of
      flow-controlled PPVA on live regeneration after hepatectomy were observed for 30
      days after hepatectomy. RESULTS: The portal vein PO(2) at the immediate time
      point and on postoperative day 30 was higher in Group A ((47.33 +/- 2.43) and
      (48.50 +/- 4.44) mmHg) than in Group B ((35.38 +/- 4.06) and (35.55 +/- 2.55)
      mmHg respectively, all P < 0.01). The mitotic index of liver cells on
      postoperative days 14 and 21 was higher in Group A (12.55% +/- 2.85% and 15.25%
      +/- 1.99% respectively) than in Group B (6.85% +/- 2.10% and 11.88% +/- 1.15%
      respectively, all P < 0.05). The regeneration rate of residual liver on
      postoperative days 14 and 21 was higher in Group A (24.56% +/- 6.15% and 70.63%
      +/- 9.83% respectively) than in Group B (11.96% +/- 5.43% and 44.92% +/- 7.42%
      respectively, P < 0.05 and P < 0.01 respectively). CONCLUSION: Flow-controlled
      PPVA can promote liver regeneration after hepatectomy and prevent liver failure
      in minipigs with chronic obstructive jaundice.

PMID- 22882853
TI  - EGB761 on retinal light injury in rats.
AB  - BACKGROUND: Retinal light injury can lead to degeneration of the photoreceptor
      cell layer. It has been hypothesized that the mechanism for this process is the
      photochemical damage. Ginkgo balboa extract (Ginkgo biloba extract EGB761) EGB761
      is a free radical scavenger. The purpose of this study was to investigate the
      possible effect of orally administered EGB761 on retinal light damage of mouse
      photoreceptor cells. METHODS: Kunming mice were randomly chosen for the following
      groups containing 20 animals in each: control group, light damage group, saline
      control group, and drug treatment group. The drug treatment group and saline
      control group were given daily gavage of EGB761 (150 mg*kg(-1)*d(-1)) one week
      before light exposure. At 7, 14, and 30 days after light exposure, animals were
      sacrificed and eyes were examined by light microscopy, electron microscopy, and
      retinal histopathology using in situ detection of apoptotic cells. RESULTS: In
      the light damage group after 7 days there was visible edema, and the outer
      nuclear layer appeared withered with deeply stained dead cells, leaving only a
      thin nuclear layer of 7 - 8 cells. After 14 days, the photoreceptor cell layer
      disappeared, leaving only the outer nuclear layer of 1 - 3 cells with an average
      thickness of (37.988 +/- 1.207) um. The average thickness of the retina was
      (126.32 +/- 2.31) um. In the drug treatment group, the photoreceptor cell layer
      and outer nuclear layer damage were significantly lower than the saline group (t
      = 21.993, P < 0.001), demonstrating that EGB761, especially at 14 days after
      light exposure, can reduce retinal light damage in mice. CONCLUSION: Oral
      administration of EGB761 can partially inhibit apoptosis of photoreceptor cells,
      resulting in increased photoreceptor cell survival.

PMID- 22882854
TI  - Methanesulfonic acid sodium salt protects retina from acute light damage in mice.
AB  - BACKGROUND: Methanesulfonic acid sodium salt (Dipyrone), an antipyretic and
      analgesic drug, has been demonstrated to improve cerebral ischemia through the
      inhibition of mitochondrial cell death cascades. The aim of this study was to
      evaluate the potential photoprotective activity of methanesulfonic acid sodium
      salt in a model of light-induced retinopathy. METHODS: One hundred mice were
      assigned randomly into vehicle (V), methanesulfonic acid sodium salt (D), light
      damage model plus vehicle (MV) and light damage model plus methanesulfonic acid
      sodium salt (MD) groups (n = 25 each). In the MD group, methanesulfonic acid
      sodium salt (100 mg/kg) was administered by intraperitoneal injection 30 minutes
      before light exposure. Twenty-four hours after light exposure, hematoxylin and
      eosin staining and transmission electron microscopy (TEM) were used for
      histological evaluation. The thickness of the outer plus inner-segment and outer
      nuclear layer was measured on sections parallel to the vertical meridian of the
      eye at a distance of 1000 mm from the optic nerve. Electroretinography (ERG) test
      was performed to assess the functional change. The morphology of mitochondria was
      also revealed by TEM. Finally, the expression of cytochrome c (CytC) and the
      relative apoptotic proteins were detected by Western blotting, and the
      interaction between mitochondrial proteins was investigated by co
      immunoprecipitation. RESULTS: The photoreceptor inner and outer segments of the
      MV group were significantly disorganized than the MD group. The thicknesses of
      the outer plus inner-segment layers and the outer nuclear layer, and the
      amplitudes of the a and b waves of the scotopic ERG response markedly decreased
      in the MV group compared to those in the MD group (P < 0.05). TEM examination
      revealed that the mitochondria of the MV group were distinctly swollen and
      contained disrupted cristae. In contrast, the morphology of mitochondria in the
      MD group was unaffected. Western blotting analysis showed that CytC, apoptosis
      proteinase activating factor-1 (Apaf-1), caspase 3, p53, p53-upregulated
      modulator of apoptosis (PUMA), Bax, and Bad were increased, whereas the anti
      apoptotic proteins Bcl-2 and Bcl-X(L) were significantly decreased in the MV
      group than the MD group. Co-immunoprecipitation detection revealed that PUMA
      immunoreactivity precipitated by Bcl-X(L) decreased, whereas Bax immunoreactivity
      precipitated by Bcl-X(L) increased in the MD group compared to those in the MV
      group. CONCLUSION: Methanesulfonic acid sodium salt is an effective
      photoprotective agent against light-induced retinopathy through the inhibition of
      CytC-mediated mitochondrial impairment.

PMID- 22882855
TI  - Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic
      nuclear factor-kappa B and cyclooxygenases-2 expression in rats.
AB  - BACKGROUND: Pioglitazone is effective in nonalcoholic steatohepatitis (NASH), but
      the mechanisms of action are not completely understood. This study was designed
      to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF
      kappaB) and cyclooxygenases-2 (COX-2) expression in NASH rats. METHODS: Thirty
      Sprague-Dawley male rats were randomly assigned to a control group (n = 10), NASH
      group (n = 10), and pioglitazone treatment group (n = 10). Liver tissues were
      processed for histology by hematoxylin & eosin and Masson stained. Serum alanine
      aminotransferase (ALT), cholesterol, triglyceride, fasting blood glucose (FBG),
      fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme
      activities, tumor necrosis factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2))
      levels in serum and liver were measured. The mRNA and protein expression of
      peroxisome proliferator-activated receptor gamma (PPARgamma), NF-kappaB and COX-2
      were determined by real-time polymerase chain reaction, Western blotting and
      immunohistochemistry. One-way analysis of variance (ANOVA) and Wilcoxon's signed
      rank test was used for the statistical analysis. RESULTS: There were severe
      steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats.
      After pioglitazone treatment, steatosis, inflammation and fibrosis were
      significantly improved compared with the NASH group (chi(2) = 20.40, P < 0.001;
      chi(2) = 20.17, P < 0.001; chi(2) = 13.98, P = 0.002). Serum ALT, cholesterol,
      triglyceride, FBG, FINS levels were significantly elevated in the NASH group (P <
      0.05). In the NASH group, total anti-oxidation competence (T-AOC), superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and
      malondialdehyde (MDA) levels in serum and liver were conspicuous disordered than
      those parameters in the control group. Meanwhile, TNF-alpha and PGE(2) levels in
      serum and liver were significantly increased compared with the control group.
      Immunohistochemistry showed NF-kappaB and COX-2 expression in liver was
      significantly elevated. However, PPAR? level was decreased in the NASH group.
      Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2
      were increased in the NASH group compared with the control group (0.57 +/- 0.08
      vs. 2.83 +/- 0.24; 0.38 +/- 0.03 vs. 1.00 +/- 0.03, P < 0.001 and P = 0.004,
      respectively). After pioglitazone intervention, all of those parameters markedly
      improved (P < 0.05 or P < 0.01). CONCLUSION: Down-regulating hepatic NF-kappaB
      and COX-2 expression, at least in part, is one of the possible therapeutic
      mechanisms of pioglitazone in NASH rats.

PMID- 22882856
TI  - Epidermal growth factor receptor-targeted ultra-small superparamagnetic iron
      oxide particles for magnetic resonance molecular imaging of lung cancer cells in
      vitro.
AB  - BACKGROUND: Magnetic resonance (MR) molecular imaging can detect abnormalities
      associated with disease at the level of cell and molecule. The epidermal growth
      factor receptor (EGFR) plays an important role in the development of lung cancer.
      This study aimed to explore new MR molecular imaging targeting of the EGFR on
      lung cancer cells. METHODS: We attached ultra-small superparamagnetic iron oxide
      (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide
      method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the
      latter as a control reagent, and determined concentrations according to the Fe
      content. Lung cancer A549 cells were cultured and immunocytochemistry (SP) was
      used to detect the expression of EGFR on cells. We detected the binding rate of
      C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We
      cultured A549 cells with C225-USPIO at a Fe concentration of 50 ug/ml and assayed
      the binding of C225-USPIO after 1 hour with Prussian blue staining and
      transmission electron microscopy (TEM). We determined the effects on imaging of
      the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the
      cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The
      scanning sequences included axial T1WI, T2WI. RESULTS: Immunocytochemical
      detection of lung cancer A549 cells found them positive for EGFR expression.
      Immunofluorescence staining and flow cytometry after cultivation with different
      concentrations of C225-USPIO showed the binding rate higher than the control.
      Prussian blue staining and transmission electron microscopy revealed that in the
      C225-USPIO contrast agent group of cells the particle content of Fe in
      cytoplasmic vesicles or on surface was more than that in the control group. The
      4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of
      cells decreased significantly more than in unlabeled cells, but there was no
      significant difference between the time gradients. CONCLUSIONS: We successfully
      constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549
      lung cancer cells. The imaging agent showed good targeting effect and
      specificity, and reduced MRI T2 value significantly, thus such molecular contrast
      agents could provide a new way to measure EGFR levels.

PMID- 22882857
TI  - FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7
      breast cancer cells.
AB  - BACKGROUND: Id3 plays a key role in the progression of breast cancer. Previously,
      four and a half LIM protein (FHL2) was identified as a repressor of Id family
      proteins by interacting with them. This study aimed to investigate the effects of
      FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human
      breast cancer cells. METHODS: Cell transfection was performed with SuperFect
      reagent. Stable transfectants that overexpressed Id3 were obtained by selection
      on G418. The level of Id3 protein was determined by Western blotting analysis.
      Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47
      mediated transcriptional activity in MCF-7 human breast cancer cells. The MTT
      assay was used to measure cell proliferation. The transwell assay was used to
      measure the invasive capacity of MCF-7 cancer cells. RESULTS: Id3 markedly
      repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47
      in MCF-7 cells. This Id3-mediated repression was effectively antagonized by FHL2.
      Overexpression of Id3 markedly promoted the proliferation and invasive capacity
      of MCF-7 cells; however, these effects were significantly suppressed by the
      overexpression of FHL2. CONCLUSIONS: FHL2 can inhibit the proliferation and
      invasive growth of human breast cancer cells by repressing the functional
      activity of Id3. The functional roles of FHL2-Id3 signaling in the development of
      human breast cancer need further research.

PMID- 22882859
TI  - Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee
      arthroplasty: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Enoxaparin is routinely used for prevention of venous thromboembolism
      (VTE) after total hip or knee arthroplasty. The purpose of this study was to
      compare the efficacy and safety of apixaban, a newly oral direct inhibitor of
      factor Xa versus enoxaparin. METHODS: We performed a meta-analysis of relevant
      randomized-controlled trials (RCTs) identified in PubMed, Cochrane Library,
      Embase China Biological Medical Literature database, Countries Journal full-text
      database, VIP database, and WanFang database. The primary efficacy outcome for
      our meta-analysis was all VTE and all-cause mortality. The secondary efficacy
      outcomes included major VTE, non-fatal pulmonary embolism, and mortality. The
      primary safety outcome was bleeding events, categorized as major, clinically
      relevant non-major, or minor events. RESULTS: Four RCTs, involving 14 065
      patients, were included in our meta-analysis. Compared to enoxaparin,
      thromboprophylaxis with apixaban was associated with significantly fewer VTE and
      all-cause mortality (8346 patients, risk ratio (RR): 0.63, 95%CI 0.42 - 0.95) and
      similar incidence of bleeding events (major bleeding, 11 525 patients, RR 0.76,
      95%CI 0.43 - 1.33; clinically relevant non-major bleeding, 11 525 patients, RR
      0.83, 95%CI 0.69 - 1.01; and minor bleeding, 11 828 patients, RR 0.93, 95%CI 0.79
      - 1.09). However, our meta-analysis revealed similar effects of apixaban with
      enoxaparin for thromboprophylaxis with regard to the secondary efficacy outcomes.
      CONCLUSIONS: Apixaban was more effective than recommended dose of enoxaparin and
      had a similar safety profile for thromboprophylaxis after hip and knee
      arthroplasty. But more evidence, especially well designed head-to-head RCTs, is
      needed to confirm the superior efficacy of apixaban.

PMID- 22882858
TI  - Relationship between the genetic variation in interleukin 28B and response to
      antiviral therapy in patients with chronic hepatitis C.
AB  - BACKGROUND: Genetic variations at the interleukin 28B (IL-28B) locus are
      important in predicting outcome following therapy for chronic hepatitis C virus
      (HCV) infection. The aim of this research was to evaluate the role of IL-28B
      single nucleotide polymorphism (SNP) variations in Chinese patients undergoing
      pegylated interferon-alpha plus ribavirin (PEG-IFN-alpha/RBV) treatment. METHODS:
      To determine the effect of IL-28B variation on the response to HCV therapy, these
      variants were genotyped in a cohort of 220 patients who were chronically infected
      with HCV and received combined PEG-IFN-alpha/RBV therapy. RESULTS: The
      proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6%
      respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%,
      and 23.7% respectively, in the null virological response (NVR) group; and 38.1%,
      52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic
      regression analysis showed that, compared to those having the CC genotype, CT
      heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12
      29.11, P = 1.5*10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1*10(-4)
      respectively). The RNA quantification assay showed that patients with genotype CC
      exhibited much higher levels of IL-28 expression than those with genotype CT or
      TT (P < 0.001). CONCLUSIONS: The IL-28B SNP rs12979860 genotype was related to
      the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had
      higher rates of SVR than those with the CT or TT genotype, and the CC genotype
      revealed a significantly higher level of IL-28 mRNA expression.

PMID- 22882860
TI  - High mobility group box 1 protein: possible pathogenic link to atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained dysrhythmia in clinical
      practice. The bulk of evidence suggests that inflammatory processes, oxidative
      stress and matrix metalloproteinase are associated with development of AF.
      However, these agents may be involved in high mobility group box 1 protein
      (HMGB1). We hypothesized that HMGB1 may be a possible pathogenic link to AF. A
      growing body of evidence supports these hypotheses. First, the level of serum
      HMGB1 is significantly increased in patients with AF including paroxysmal and
      persistent AF. Second, HMGB1 has been identified as a new pro-inflammatory
      cytokine in cardiovascular diseases, along with tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, and C-reactive protein, and there is cross-talk
      between HMGB1 and inflammatory cytokines. Third, oxidative stress is involved in
      the release of the pro-inflammatory cytokine, HMGB1, indicating there is cross
      talk between oxidative stress and inflammation, and oxidative stress may
      reinforce the effect of inflammation on the pathogenesis of AF and inflammation
      may play a more important role in the pathogenesis of AF. Fourth, HMGB1 can
      promote matrix metalloproteinase-9 upregulation and activation. Fifth, HMGB1
      receptors (receptor for advanced glycation end products, Toll-like receptor-2,4)
      may mediate the atrial structural remodeling or be up-regulated in patients with
      non-valvular AF. These results suggest that HMGB1 may participate in the
      pathogenesis of AF and provide a potential target for pharmacological
      interruption of AF.

PMID- 22882861
TI  - Epigenetics of hepatocellular carcinoma: a new horizon.
AB  - Epigenetic changes refer to stable alterations in gene expression with no
      underlying modifications in the genetic sequence itself. It has become clear that
      not only gene variations but also epigenetic modifications may contribute to
      varied diseases, including cancer. This review will provide an overview of how
      epigenetic factors, including genomic DNA methylation, histone modifications, and
      miRNA regulation, contribute to hepatocellular carcinoma (HCC) dissemination,
      invasion, and metastasis. Additionally, the reversal of dysregulated epigenetic
      changes has emerged as a potential strategy for the treatment of HCC, and we will
      summarize the latest epigenetic therapies for HCC.

PMID- 22882862
TI  - Gray matter involvement in patients with multiple sclerosis as shown by magnetic
      resonance imaging.
AB  - OBJECTIVE: To summarize the main findings seen on conventional and advanced
      magnetic resonance imaging (MRI) used to assess gray matter (GM) involvement in
      patients with multiple sclerosis (MS). DATA SOURCES: The data used in this review
      were obtained mainly from studies reported in the PubMed database using the terms
      of multiple sclerosis, gray matter, magnetic resonance imaging. STUDY SELECTION:
      Relevant literatures on studies of GM involvement in MS patients were identified,
      retrieved and reviewed. RESULTS: MS is the most common chronic, disabling central
      nervous system disease in young adults. Although traditional thinking has
      considered MS to be a chronic inflammatory demyelinating condition affecting
      solely the white matter (WM) of the central nervous system, over the last few
      years it has been shown that GM pathology is also common and extensive. GM
      demyelinating lesions can not only be found in the cerebral cortex but also in
      the deep gray nuclei. Apart from focal demyelinated lesions, diffuse neuronal
      loss and atrophy is also present in the GM of MS patients. CONCLUSIONS: The
      widespread use of conventional and quantitative MRI based techniques in MS has
      led to an improved understanding of the mechanisms underlying the inflammatory
      and neurodegenerative processes of the disease. However, more researches are
      needed to unravel GM pathology in MS patients, which at present remains
      enigmatic.

PMID- 22882863
TI  - Expression of connexin 36 in central nervous system and its role in epileptic
      seizure.
AB  - OBJECTIVE: This review discusses the experimental and clinical studies those show
      the expression of connexin 36 in the central nervous system and the possible role
      of connexin 36 in epileptic seizure. DATA SOURCES: All articles used in this
      review were mainly searched from PubMed published in English from 1996 to 2012.
      STUDY SELECTION: Original articles and reviews were selected if they were related
      to the expression of connexin 36 in the central nervous system and its role in
      epilepsy. RESULTS: The distribution of connexin 36 is developmentally regulated,
      cell-specific and region-specific. Connexin 36 is involved in some neuronal
      functions and epileptic synchronization. Changes in the connexin 36 gene and
      protein were accompanied by seizures. Selective gap junction blockers have
      exerted anticonvulsant actions in a variety of experiments examined in both
      humans and experimental animals. CONCLUSIONS: Connexin 36 plays an important role
      in both physiological and pathological conditions in the central nervous system.
      A better understanding of the role of connexin 36 in seizure activity may
      contribute to the development of new therapeutic approaches to treating epilepsy.

PMID- 22882864
TI  - Hepatitis B virus/human immunodeficiency virus coinfection: interaction among
      human immunodeficiency virus infection, chronic hepatitis B virus infection, and
      host immunity.
AB  - OBJECTIVE: This review discusses progress in the studies of hepatitis B virus
      (HBV)/human immunodeficiency virus (HIV) coinfection and focuses on the
      interaction among HIV infection, chronic HBV infection, and host immunity. DATA
      SOURCES: Data and studies published mainly from 2008 to 2011 were selected using
      PubMed. STUDY SELECTION: Original articles and critical reviews concerning
      HBV/HIV coinfection and HBV and HIV pathogenesis were selected. RESULTS: HIV may
      accelerate HBV progression by lowering CD4 count, weakening HBV-specific
      immunity, "enriching" HBV mutants, causing immune activation, etc. On the other
      hand, HBV may enhance HIV replication by activating HIV long terminal repeat
      (LTR) with X protein (HBX) and cause immune activation in synergy with HIV.
      Paradoxically, HBV may also inhibit HIV dissemination via dendritic cells.
      CONCLUSIONS: The interaction among HIV, HBV, and host immunity remains poorly
      understood. Further research is warranted to elucidate the detailed molecular
      mechanisms and to translate these mechanisms into clinical practice.

PMID- 22882865
TI  - Downregulating activated epidermal growth factor receptor has no effect on RBM5
      expression.
AB  - BACKGROUND: We were interested in determining how the tumor suppressor gene RBM5
      is regulated in lung cancers. Previous studies suggested that the gene expression
      is related to histological subtype and smoking exposure, since in small cell lung
      cancers the RBM5 gene is deleted whereas in non-small cell lung carcinomas
      (NSCLC) RBM5 expression is reduced. Of particular interest was the recent finding
      that in lung adenocarcinomas, a histological subtype of NSCLC, smoking exposure
      correlated with mutational activity in the transforming growth factor alpha (TGF
      a) signaling pathway. Lung adenocarcinomas from smokers were associated with
      activating KRAS mutations, whereas lung adenocarcinomas from never-smokers were
      associated with activating epidermal growth factor receptor (EGFR) mutations. We
      hypothesized that inhibition of RBM5 in lung adenocarcinomas is achieved
      indirectly via these activating mutations. The objective of the research
      described herein was to determine if EGFR activation and RBM5 expression are
      negatively correlated. METHODS: EGFR expression in the lung adenocarcinoma cell
      line NCI-H1975 was inhibited using small interfering RNA. RBM5 expression was
      examined by real-time quantitative polymerase chain reaction and Western
      blotting. RESULTS: Reduced EGFR expression did not correlate with any change in
      RBM5 expression at either the RNA or protein level. CONCLUSION: These results
      suggest that RBM5 expression is not directly regulated by EGFR in non-smoker
      related lung adenocarinomas, and that some other mechanism operates to inhibit
      either the expression or function of this potential tumour suppressor in lung
      cancers that retain the RBM5 gene.

PMID- 22882866
TI  - Pure transperitoneal laparoscopic correction of retrocaval ureter.
AB  - BACKGROUND: Retrocaval ureter is a rare congenital abnormality. Operative repair
      is always suggested in cases of significant functional obstruction. Laparoscopic
      procedures have been employed as the minimally invasive therapeutic option for
      retrocaval ureter. However, the laparoscopic techniques for retrocaval ureter
      might be technically challenging to some surgeons. The aim of this article was to
      present our experience and surgical techniques of pure transperitoneal
      laparoscopic pyelopyelostomy and ureteroureterostomy in nine patients with
      retrocaval ureter. METHODS: A total of nine patients of retrocaval ureter
      underwent pure laparoscopic pyelopyelostomy or ureteroureterostomy. The operation
      was performed with the patients placed in the 70-degree lateral decubitus
      position via a three port transperitoneal approach with two 10-mm and one 5-mm
      ports. The distal part of the dilated renal pelvis was transected at the
      ureteropelvic junction and the ureter was relocated anterior to the inferior vena
      cava. The tension-free pyeloureteral or ureteroureteral anastomosis was completed
      with the intracorporal freehand suturing and in situ knot-tying techniques
      combined with interrupted and continuous fashion. A double J ureteral stent was
      inserted in an antegrade manner during laparoscopy. Intravenous urography or
      computerized tomography and renal ultrasonography were performed after 3 months
      postoperatively. RESULTS: All operations were completed laparoscopically, and no
      open conversion was required. The mean operative time was 135 minutes (range, 70 
      250 minutes), with minimal blood loss (less than 60 ml). No intra-operative
      complications or significant bleeding occurred. All patients presented mild
      postoperative pain and quick convalescence. The symptoms disappeared and
      hydronephrosis decreased substantially after surgery. CONCLUSIONS: Pure
      transperitoneal laparoscopic correction for retrocaval ureter was associated with
      an excellent outcome, minimal invasiveness and short hospital stay. It is
      technically feasible and reliable for retrocaval ureter treatment. Laparoscopic
      surgery could be the standard treatment for retrocaval ureter.

PMID- 22882867
TI  - Sclerosing angiomatoid nodular transformation of the spleen: report of five cases
      and review of literature.
AB  - Sclerosing angiomatoid nodular transformation (SANT) of the spleen, a newly
      defined primary lesion of the spleen, is very rare. Immunohistochemistry is the
      only way to confirm the diagnosis of SANT. We present the clinical
      characteristics and postoperative outcomes of five SANT cases that underwent
      splenectomy from January 2007 to October 2010. Although SANT had specific imaging
      findings, differential diagnosis from other splenic tuomrs or malignant lesions
      preoperatively was difficult. The hand-assisted laparoscopic splenectomy was a
      useful and effective technique for the management and postoperative diagnosis of
      SANT. All SANT patients had good prognosis without recurrence after splenectomy.

PMID- 22882868
TI  - Systemic sclerosis with portal hypertensive ascites responded to corticosteroid
      treatment.
AB  - We describe a case of systemic sclerosis (SSc) complicated with portal
      hypertensive ascites which did not improve with diuretics and ascitic drainage.
      When corticosteroid added, her ascites diminished dramatically. Though portal
      hypertension can be imputed to other causes, such as polycystic liver in this
      case, it can occur in limited SSc with positive anti-centromere antibody and
      respond to corticosteroid treatment.

PMID- 22882869
TI  - Disseminated cryptococcal lymphadenitis with negative latex agglutination test.
AB  - We reported an unusual case of disseminated cryptococcal lymphadenitis in an
      immunocompetent host who presented with fever and lymphadenopathy, which were the
      only two symptoms and signs. Latex agglutination test of serum and cerebrospinal
      fluid (CSF) were negative, while lymph node biopsy showed Cryptococcus
      neoformans. A diagnosis of disseminated cryptococcal lymphadenitis was made. Then
      the patient was treated with amphotericin B for 15 days as initial therapy and
      itraconazole for 6 months as maintenance therapy respectively. The patient
      received re-examination per 6 months and was followed up for 2 years. Swollen
      lymph nodes diminished gradually, and no fever or other symptoms were found.
      Latex agglutination test of serum and CSF were negative throughout the follow-up
      period, and anti-HIV, syphilis and tuberculosis antibody were all negative.

PMID- 22882871
TI  - Abuse and smoking cessation in clinical practice.
AB  - AIMS AND OBJECTIVES: This discursive paper explores issues of abuse during
      smoking cessation counselling. BACKGROUND: During a training session for a
      smoking cessation intervention pilot study, nurses expressed concerns about
      issues of abuse that had previously surfaced during cessation counselling in
      their practice. Abused women are more likely to smoke. As guidelines recommend
      integrating cessation interventions into practice, issues of abuse are likely to
      surface. METHODS: A literature review and synthesis of abuse and smoking
      cessation was undertaken to arrive at recommendations for practice. RESULTS:
      There are a few suggestions about how to manage abuse within cessation
      counselling, but none have been studied: (1) integrate stress-management
      strategies, (2) assess for abuse, (3) provide separate interventions for partners
      to create a safe environment, and (4) develop interventions that consider the
      relationship couples have with tobacco. However, coping strategies alone do not
      address abuse, screening without treatment is not helpful, and partner
      interventions assume both partners are open to quitting/counselling. In contrast,
      as with all clinical practice, abuse and cessation would be considered separate
      but intertwined problems, and following best practice guidelines for abuse would
      provide the guidance on how to proceed. After care has been taken to address
      abuse, it is the patient's decision whether to continue with cessation
      counselling. CONCLUSION: Guidelines addresses both care planning and the
      ethical/legal issues associated with the disclosure of abuse and provide a
      practical tool for addressing abuse that obviates the need to tailor cessation
      interventions to abuse. RELEVANCE TO CLINICAL PRACTICE: This paper clarifies a
      relationship between smoking and abuse and the subsequent implications for
      smoking cessation interventions and highlights the importance of addressing abuse
      and smoking cessation separately, even though they are interrelated problems. It
      provides nurses with appropriate initial responses when abuse is disclosed during
      an unexpected encounter such as during a smoking cessation intervention.

PMID- 22882870
TI  - Identification of the dehydrin gene family from grapevine species and analysis of
      their responsiveness to various forms of abiotic and biotic stress.
AB  - BACKGROUND: Dehydrins (DHNs) protect plant cells from desiccation damage during
      environmental stress, and also participate in host resistance to various
      pathogens. In this study, we aimed to identify and characterize the DHN gene
      families from Vitis vinifera and wild V. yeshanensis, which is tolerant to both
      drought and cold, and moderately resistant to powdery mildew. RESULTS: Four DHN
      genes were identified in both V. vinifera and V. yeshanensis, which shared a high
      sequence identity between the two species but little homology between the genes
      themselves. These genes were designated DHN1, DHN2, DHN3 and DHN4. All four of
      the DHN proteins were highly hydrophilic and were predicted to be intrinsically
      disordered, but they differed in their isoelectric points, kinase selectivities
      and number of functional motifs. Also, the expression profiles of each gene
      differed appreciably from one another. Grapevine DHN1 was not expressed in
      vegetative tissues under normal growth conditions, but was induced by drought,
      cold, heat, embryogenesis, as well as the application of abscisic acid (ABA),
      salicylic acid (SA), and methyl jasmonate (MeJA). It was expressed earlier in V.
      yeshanensis under drought conditions than in V. vinifera, and also exhibited a
      second round of up-regulation in V. yeshanensis following inoculation with
      Erysiphe necator, which was not apparent in V. vinifera. Like DHN1, DHN2 was
      induced by cold, heat, embryogenesis and ABA; however, it exhibited no
      responsiveness to drought, E. necator infection, SA or MeJA, and was also
      expressed constitutively in vegetative tissues under normal growth conditions.
      Conversely, DHN3 was only expressed during seed development at extremely low
      levels, and DHN4 was expressed specifically during late embryogenesis. Neither
      DHN3 nor DHN4 exhibited responsiveness to any of the treatments carried out in
      this study. Interestingly, the presence of particular cis-elements within the
      promoter regions of each gene was positively correlated with their expression
      profiles. CONCLUSIONS: The grapevine DHN family comprises four divergent members.
      While it is likely that their functions overlap to some extent, it seems that
      DHN1 provides the main stress-responsive function. In addition, our results
      suggest a close relationship between expression patterns, physicochemical
      properties, and cis-regulatory elements in the promoter regions of the DHN genes.

PMID- 22882872
TI  - Undergraduate medical students' perceptions, attitudes, and competencies in
      evidence-based medicine (EBM), and their understanding of EBM reality in Syria.
AB  - BACKGROUND: Teaching evidence-based medicine (EBM) should be evaluated and guided
      by evidence of its own effectiveness. However, no data are available on adoption
      of EBM by Syrian undergraduate, postgraduate, or practicing physicians. In fact,
      the teaching of EBM in Syria is not yet a part of undergraduate medical
      curricula. The authors evaluated education of evidence-based medicine through a
      two-day intensive training course. METHODS: The authors evaluated education of
      evidence-based medicine through a two-day intensive training course that took
      place in 2011. The course included didactic lectures as well as interactive hands
      on workshops on all topics of EBM. A comprehensive questionnaire, that included
      the Berlin questionnaire, was used to inspect medical students' awareness of,
      attitudes toward, and competencies' in EBM. RESULTS: According to students,
      problems facing proper EBM practice in Syria were the absence of the following:
      an EBM teaching module in medical school curriculum (94%), role models among
      professors and instructors (92%), a librarian (70%), institutional subscription
      to medical journals (94%), and sufficient IT hardware (58%). After the course,
      there was a statistically significant increase in medical students' perceived
      ability to go through steps of EBM, namely: formulating PICO questions (56.9%),
      searching for evidence (39.8%), appraising the evidence (27.3%), understanding
      statistics (48%), and applying evidence at point of care (34.1%). However, mean
      increase in Berlin scores after the course was 2.68, a non-statistically
      significant increase of 17.86%. CONCLUSION: The road to a better EBM reality in
      Syria starts with teaching EBM in medical school and developing the proper
      environment to facilitate transforming current medical education and practice to
      an evidence-based standard in Syria.

PMID- 22882873
TI  - Rational formulation design.
AB  - To be efficacious and to satisfy the requirements for claim substantiation, a
      cosmetic formulation must achieve effective targeting of an active in the skin.
      Although the basic principles governing the skin permeation and disposition of
      molecules have been known for many years, attention has been far less focused on
      the role of the vehicle, particularly at cosmetically relevant doses. In this
      article, we discuss the necessity to understand the fate of the formulation
      components as well as the active once applied onto skin. Recent data confirm that
      the residence time of the formulation constituents can have a profound impact on
      the fate of the active. Approaches to identify the ideal vehicle for skin
      delivery are considered critically, specifically the recent work on 'formulating
      for efficacy' (FFE) by the late Johann Wiechers. Essentially, FFE aims to match
      the active with the optimal vehicle for skin delivery based on matching
      polarity/solubility values of the trinity of skin, active and vehicle. The
      emerging importance of techniques that provide insight to how the vehicle
      distributes in and on skin is highlighted.

PMID- 22882874
TI  - Infection with street strain rabies virus induces modulation of the microRNA
      profile of the mouse brain.
AB  - BACKGROUND: Rabies virus (RABV) causes a fatal infection of the central nervous
      systems (CNS) of warm-blooded animals. Once the clinical symptoms develop, rabies
      is almost invariably fatal. The mechanism of RABV pathogenesis remains poorly
      understood. Recent studies have shown that microRNA (miRNA) plays an important
      role in the pathogenesis of viral infections. Our recent findings have revealed
      that infection with laboratory-fixed rabies virus strain can induce modulation of
      the microRNA profile of mouse brains. However, no previous report has evaluated
      the miRNA expression profile of mouse brains infected with RABV street strain.
      RESULTS: The results of microarray analysis show that miRNA expression becomes
      modulated in the brains of mice infected with street RABV. Quantitative real-time
      PCR assay of the differentially expressed miRNAs confirmed the results of
      microarray assay. Functional analysis showed the differentially expressed miRNAs
      to be involved in many immune-related signaling pathways, such as the Jak-STAT
      signaling pathway, the MAPK signaling pathway, cytokine-cytokine receptor
      interactions, and Fc gamma R-mediated phagocytosis. The predicted expression
      levels of the target genes of these modulated miRNAs were found to be correlated
      with gene expression as measured by DNA microarray and qRT-PCR. CONCLUSION: RABV
      causes significant changes in the miRNA expression profiles of infected mouse
      brains. Predicted target genes of the differentially expression miRNAs are
      associated with host immune response, which may provide important information for
      investigation of RABV pathogenesis and therapeutic method.

PMID- 22882875
TI  - The rise in singleton preterm births in the USA: the impact of labour induction.
AB  - OBJECTIVE: To assess the extent to which increased rates of labour induction and
      caesarean section have contributed to the recent rise in preterm birth. DESIGN:
      National birth cohort study. SETTING: USA. POPULATION AND SAMPLE: Singleton live
      births, with primary analysis based on non-Hispanic white women. METHODS:
      Ecological study based on the 50 states and the District of Columbia during two
      time periods 10 years apart: 1992-94 and 2002-04. MAIN OUTCOME MEASURE: Preterm
      birth (live birth <37 completed weeks of gestation), based on an algorithm
      combining menstrual and clinical estimates of gestational age. RESULTS: The state
      level ecological analysis among non-Hispanic white women showed that the change
      in preterm birth rate from 1992-94 to 2002-04 was significantly associated with
      the change in rate of labour induction (r = 0.50, 95% CI 0.26-0.68), but not with
      the change in rate of caesarean delivery (r = -0.06, 95% CI -0.33 to 0.22).
      Weaker but otherwise similar associations with labour induction were observed in
      Hispanic women and in non-Hispanic black women. CONCLUSIONS: Increasing use of
      labour induction is probably an important cause of the observed increased rate in
      preterm birth.

PMID- 22882876
TI  - Qualitative inquiry into motivators for maintaining medication adherence among
      Taiwanese with schizophrenia.
AB  - Medication non-adherence is associated with higher rates of relapse in persons
      with schizophrenia. Psychiatric nurses play a significant role in facilitating
      their medication adherence. The motivators which strengthen patients with
      schizophrenia to maintain their adherence to medication have seldom been
      explored. This study aims to explore what motivates persons with schizophrenia to
      consistently maintain their medication adherence. A qualitative approach was used
      to collect data from a psychiatric day-care centre at an armed forces hospital in
      Taiwan. Ten clients agreed to undergo an in-depth interview. The data was
      analyzed by a content analysis method. Four themes were identified: (i) the
      benefits of antipsychotic medication treatment; (ii) firm and ongoing family
      support; and the Chinese values of (iii) filial piety and (iv) hope for the
      future. These findings may provide psychiatric nurses with a better understanding
      of the motivators for medication adherence in persons with schizophrenia from the
      Chinese perspective. Nurses will then be able to adjust their practice to
      facilitate patients' medication adherence.

PMID- 22882877
TI  - Prognostic value of the CAPRA clinical prediction rule: a systematic review and
      meta-analysis.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Prostate cancer is a
      significant cause of mortality among men. A number of prognostic instruments
      exist to predict the risk of recurrence among patients with localised prostate
      cancer. This systematic review examines the totality of evidence in relation to
      the predictive value of the CAPRA clinical predication rule by combining all
      studies that validate the rule. OBJECTIVES: To perform a systematic review with
      meta-analysis that assesses the 3- and 5-year predictive value of the CAPRA rule,
      a clinical prediction rule derived to predict biochemical-recurrence-free
      survival in men with localized prostate cancer after radical prostatectomy. To
      examine the predictive value of the CAPRA rule at 3 and 5 years stratified by
      risk group (0-2 low risk, 3-5 intermediate risk, 6-10 high risk). PATIENTS AND
      METHODS: A systematic literature search was performed to retrieve papers that
      validated the CAPRA score. The original derivation study was used as a predictive
      model and applied to all validation studies with observed and predicted
      biochemical-recurrence-free survival at 3 and 5 years stratified by risk group (0
      2 low, 3-5 intermediate, 6-10 high). Pooled results are presented as risk ratios
      (RRs) with 95% confidence intervals, in terms of over-prediction (RR > 1) or
      under-prediction (RR < 1) of biochemical-recurrence-free survival at 3 and 5
      years. A chi-squared test for trend was computed to determine if there was a
      decreasing trend in survival across the three CAPRA risk categories. RESULTS:
      Seven validation studies (n = 12 693) predict recurrence-free survival at 5 years
      after radical prostatectomy. The CAPRA score significantly under-predicts
      recurrence-free survival across all three risk strata (low risk, RR 0.94, 95% CI
      0.90-0.98; intermediate risk, RR 0.94, 95% CI 0.89-0.99; high risk, RR 0.72, 95%
      CI 0.60-0.85). Data on six studies (n = 6082) are pooled to predict 3-year
      recurrence-free survival. The CAPRA score correctly predicts recurrence-free
      survival in all three groups (low risk, RR 0.98, 95% CI 0.95-1.00; intermediate
      risk, RR 1.03, 95% CI 0.99-1.08; high risk, RR 0.87, 95% CI 0.73-1.05). The chi
      squared trend analysis indicates that, as the trichotomized CAPRA score
      increases, the probability of survival decreases (P < 0.001). CONCLUSIONS: The
      results of this pooled analysis confirm the ability of the CAPRA rule to
      correctly predict biochemical-recurrence-free survival at 3 years after radical
      prostatectomy. The rule under-predicts recurrence-free survival 5 years after
      radical prostatectomy across all three strata of risk.

PMID- 22882878
TI  - Persuading drivers to refrain from speeding: Effects of message sidedness and
      regulatory fit.
AB  - Building on regulatory fit theory (Higgins, 2000, 2005), we tested whether two
      sided ads were more effective than one-sided ads in changing intentions toward
      driving behavior when message recipients were high in assessment orientation
      rather than locomotion orientation. In one study either a locomotion or an
      assessment orientation were situationally induced (Study 1) and in another study
      these different orientations were chronic predispositions (Study 2). As
      predicted, both studies found that for participants high in assessment, two-sided
      ads were more effective than one-sided ads, as reflected in stronger engagement
      with the persuasive message and stronger intentions to reduce driving speed. In
      contrast, for participants high in locomotion, one-sided ads were more effective
      than two-sided ads. There was also evidence that the fit effect on intentions to
      comply was mediated by strength of engagement with the message. Implications for
      persuasion concerning driving behaviors are discussed.

PMID- 22882879
TI  - Blocking-out auditory distracters while driving: A cognitive strategy to reduce
      task-demands on the road.
AB  - The current research examined how drivers handle task-demands induced by
      listening to the radio while driving. In particular, we explored the traces of a
      possible cognitive strategy that might be used by drivers to cope with task
      demands, namely blocking-out auditory distracters. In Study 1 (N=15),
      participants listened to a radio-broadcast while watching traffic videos on a
      screen. Based on a recall task asking about what they had listened to, we created
      baseline scores reflecting the general levels of blocking-out of radio-content
      when there was no concurrent driving task accompanying the radio-listening. In
      Study 2 (N=46), participants were asked to complete two drives in the simulator:
      one drive in high-complexity traffic and another in low-complexity traffic. About
      half of the participants listened to a radio-broadcast while driving, and the
      other half drove in silence. The radio-listeners were given the same recall task
      that we had used in Study 1. The results revealed that the participants who drove
      while listening to the radio (Study 2) recalled less material from the radio
      broadcast as compared to the participants who did not drive (Study 1). In
      addition, the participants who drove while listening to the radio recalled less
      talk-radio excerpts when driving in high-complexity traffic than when driving in
      low-complexity traffic. Importantly, listening to the radio did not impair
      driving performance. Together, these findings indicate that blocking-out radio
      content might indeed be a strategy used by drivers to maintain their driving
      performance.

PMID- 22882880
TI  - In the face of chronic aspiration, prolonged ischemic time exacerbates
      obliterative bronchiolitis in rat pulmonary allografts.
AB  - Aspiration of gastric fluid into the lung mediates the development of
      obliterative bronchiolitis (OB) in orthotopic WKY-to-F344 rat pulmonary
      transplants that have been subjected to immunosuppression with cyclosporine.
      However, the contribution of ischemic time to this process remains unknown. In
      this study, the effect of long (n = 16) and short (n = 12) ischemic times
      (average of 6 h and of 73 min, respectively) on rat lung transplants receiving
      aspiration of gastric fluid was assessed. Long ischemic times (LIT) led to
      significantly (p < 0.05) greater development of OB (ratio of OB lesions/total
      airways = 0.45 +/- 0.07, mean +/- standard error) compared to short ischemic
      times (ratio = 0.19 +/- 0.05). However, the development of OB was dependent on
      aspiration, as controls receiving aspiration with normal saline showed little
      development of OB, regardless of ischemic time (p < 0.05). These data suggest
      that LIT, while insufficient by itself to lead to OB, works synergistically with
      aspiration of gastric fluid to exacerbate the development of OB.

PMID- 22882881
TI  - Standing on the threshold of change.
AB  - Tobacco use remains the nation's leading cause of preventable premature
      mortality. Lung cancer, one of the many cancers caused by tobacco use, is both
      the leading cause of cancer death in the United States and the leading cause of
      male cancer death globally. This special issue of Risk Analysis features the work
      of the National Cancer Institute's Cancer Intervention and Surveillance Modeling
      Network (CISNET), which finds that changes in Americans' smoking behaviors that
      began in the mid 1950s averted nearly 800,000 U.S. lung cancer deaths in the
      period 1975-2000 alone. However, this figure represents only about 30% of the
      lung cancer deaths that could potentially have been averted during this period.
      Despite dramatic declines in smoking prevalence since the mid 1960s, tobacco use
      is still far too common; today about one in five American adults smokes
      cigarettes. The tobacco industry's role in promoting tobacco use is now well
      documented and, as noted by the President's Cancer Panel, "can no more be ignored
      in seeking solutions to the tobacco problem than mosquitoes can be ignored in
      seeking to eradicate malaria." Recent developments, including the passage of
      legislation granting the Food and Drug Administration broad authority to regulate
      tobacco products, and the entry into force of the Framework Convention on Tobacco
      Control, an evidence-based treaty developed by the World Health Organization,
      hold great promise to more swiftly end the epidemic of lung cancer and other
      tobacco-caused diseases that exacts such a heavy toll in human suffering in the
      United States and around the world.

PMID- 22882882
TI  - Chapter 9: The MGH-HMS lung cancer policy model: tobacco control versus
      screening.
AB  - The natural history model underlying the MGH Lung Cancer Policy Model (LCPM) does
      not include the two-stage clonal expansion model employed in other CISNET lung
      models. We used the LCPM to predict numbers of U.S. lung cancer deaths for ages
      30-84 between 1975 and 2000 under four scenarios as part of the comparative
      modeling analysis described in this issue. The LCPM is a comprehensive
      microsimulation model of lung cancer development, progression, detection,
      treatment, and survival. Individual-level patient histories are aggregated to
      estimate cohort or population-level outcomes. Lung cancer states are defined
      according to underlying disease variables, test results, and clinical events. By
      simulating detailed clinical procedures, the LCPM can predict benefits and harms
      attributable to a variety of patient management practices, including annual
      screening programs. Under the scenario of observed smoking patterns, predicted
      numbers of deaths from the calibrated LCPM were within 2% of observed over all
      years (1975-2000). The LCPM estimated that historical tobacco control policies
      achieved 28.6% (25.2% in men, 30.5% in women) of the potential reduction in U.S.
      lung cancer deaths had smoking had been eliminated entirely. The hypothetical
      adoption in 1975 of annual helical CT screening of all persons aged 55-74 with at
      least 30 pack-years of cigarette exposure to historical tobacco control would
      have yielded a proportion realized of 39.0% (42.0% in men, 33.3% in women). The
      adoption of annual screening would have prevented less than half as many lung
      cancer deaths as the elimination of cigarette smoking.

PMID- 22882883
TI  - Chapter 10: A macro-model of smoking and lung cancer: examining aggregate trends
      in lung cancer rates using the CPS-I and CPS-II and two-stage clonal expansion
      models.
AB  - Past studies have examined the relationship of lung cancer to smoking using
      longitudinal data for select samples. This study applies the two-stage clonal
      expansion (TSCE) model to U.S. +xsmoking data over a 25-year period. Smoking Base
      Case (SBC) data on actual smoking duration and intensity from the years 1975-2000
      are applied by gender to separate TSCE models, which are then calibrated to
      historical trends in lung cancer death rates using regression analysis. The
      uncalibrated and calibrated TSCE models are also applied to SBC data for two
      scenarios: (1) no tobacco control and (2) complete tobacco control. The results
      are used to develop estimates of the number of lives saved as a result of tobacco
      control and how many lives would be saved if cigarette use had ceased in 1965.
      Predictions of lung cancer from the TSCE models with CPS-II and the CPS-I data
      for males and especially females are considerably below historical rates with the
      deviations from historical rates increasing over time. Residual trends unrelated
      to the smoking models were also found. Tobacco control activities saved
      approximately 625,000 lives between the years 1975 and 2000. An additional
      2,110,000 lives would have been saved if all smoking was stopped in 1965. Tobacco
      control has successfully prevented lung cancer deaths, but many more lives could
      be saved with further reductions in smoking rates. Systematic biases were
      observed from TSCE models using CPS-I and CPS-II data to estimate smoking-related
      lung cancer deaths.

PMID- 22882884
TI  - Chapter 2: Birth-cohort-specific estimates of smoking behaviors for the U.S.
      population.
AB  - We present methods for estimating five-year birth-cohort-specific trends in
      smoking behavior for individuals born between 1910 and 1984. We combine cross
      sectional survey data on smoking behavior from the National Health Interview
      Surveys (NHIS) conducted between 1965 and 2001 into a single data set. The
      cumulative incidence of smoking by year of age and calendar year is constructed
      for each birth cohort from this data set and the effect of differential mortality
      on ever smoking prevalence is adjusted by modeling the ever smoking prevalence of
      each cohort for each survey year and back extrapolating that effect to age 30.
      Cumulative incidence is then scaled to match the ever smoking prevalence at age
      30. Survival analyses generate the cumulative cessation among ever smokers across
      year of age and calendar year and are used to estimate current smoking
      prevalence. Data from Substance Abuse and Mental Health Services Administration
      (SAMHSA) National Survey on Drug Use and Health is used to divide those
      initiating smoking into quintiles of number of cigarettes smoked per day (CPD)
      and the mean CPD for each quintile in each calendar year is estimated from the
      NHIS data. For five-year birth cohorts of white, african-american, Hispanic and
      all race/ethnicity groupings of males and females born between 1910 and 1984,
      estimates are provided for prevalence of current and ever smoking, incidence of
      cessation, incidence of initiation, and the distribution of smoking duration and
      CPD for each calendar year and each single year of age through the year 1999. We
      believe that we are the first to provide birth-cohort-specific estimates of
      smoking behaviors for the U.S. population that include distributions of duration
      of smoking and number of cigarettes per day. These additional elements
      substantively enhance the utility of these estimates for estimating lung cancer
      risks.

PMID- 22882885
TI  - Chapter 11: Rice-MD Anderson lung cancer model.
AB  - The Rice-MD Anderson group uses a two-stage clonal expansion (TSCE) model of lung
      cancer mortality calibrated to a combination of MD Anderson case-control data on
      smoking histories and lung cancer mortality/incidence rate data collected from
      prospective cohorts in order to predict risk of lung cancer. This model is used
      to simulate lung cancer mortality in the U.S. population under the three
      scenarios of CISNET lung group's smoking base case project in order to estimate
      the effect of tobacco control policy on lung cancer mortality rates. Simulation
      results show that tobacco control policies have achieved 35% of the reduction in
      lung cancer mortality that would have resulted from cessation of all smoking in
      1965.

PMID- 22882886
TI  - Chapter 12: Yale lung cancer model.
AB  - The age-period-cohort model is known to provide an excellent description of the
      temporal trends in lung cancer incidence and mortality. This analytic approach is
      extended to include the contribution of carcinogenesis models for smoking.
      Usefulness of this strategy is that it offers a way to temporally calibrate a
      model that is fitted to population data and it can be readily adopted for the
      consideration of many different models. In addition, it provides diagnostics that
      can suggest temporal limitations of a particular carcinogenesis model in
      describing population rates. Alternative carcinogenesis models can be embedded
      within this framework. The two-stage clonal expansion model is implemented here.
      The model was used to estimate the impact of tobacco control after dissemination
      of knowledge of the harmful effects of cigarette smoking by comparing the
      observed number of lung cancer deaths to those expected if there had been no
      control compared to an ideal of complete control in 1965. Results indicate that
      35.2% and 26.5% of lung cancer deaths that could have been avoided actually were
      for males and females, respectively.

PMID- 22882888
TI  - Chapter 14: Comparing the adequacy of carcinogenesis models in estimating U.S.
      population rates for lung cancer mortality.
AB  - The relationship between smoking and lung cancer is well established and cohort
      studies provide estimates of risk for individual cohorts. While population trends
      are qualitatively consistent with smoking trends, the rates do not agree well
      with results from analytical studies. Four carcinogenesis models for the effect
      of smoking on lung cancer mortality were used to estimate lung cancer mortality
      rates for U.S. males: two-stage clonal expansion and multistage models using
      parameters estimated from two Cancer Prevention Studies (CPS I and CPS II).
      Calibration was essential to adjust for both shift and temporal trend. The age
      period-cohort model was used for calibration. Overall, models using parameters
      derived from CPS I performed best, and the corresponding two-stage clonal
      expansion model was best overall. However, temporal calibration did significantly
      improve agreement with the population rates, especially the effect of age and
      cohort.

PMID- 22882887
TI  - Chapter 13: CISNET lung models: comparison of model assumptions and model
      structures.
AB  - Sophisticated modeling techniques can be powerful tools to help us understand the
      effects of cancer control interventions on population trends in cancer incidence
      and mortality. Readers of journal articles are, however, rarely supplied with
      modeling details. Six modeling groups collaborated as part of the National Cancer
      Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) to
      investigate the contribution of U.S. tobacco-control efforts toward reducing lung
      cancer deaths over the period 1975-2000. The six models included in this
      monograph were developed independently and use distinct, complementary approaches
      toward modeling the natural history of lung cancer. The models used the same data
      for inputs, and agreed on the design of the analysis and the outcome measures.
      This article highlights aspects of the models that are most relevant to
      similarities of or differences between the results. Structured comparisons can
      increase the transparency of these complex models.

PMID- 22882889
TI  - Chapter 15: Impact of tobacco control on lung cancer mortality in the United
      States over the period 1975-2000--summary and limitations.
AB  - BACKGROUND: A consortium of six research groups estimated the impact on lung
      cancer mortality of changes in smoking behavior that began around the publication
      of the Surgeon General's report (SGR). This chapter presents the results of that
      effort. We quantified the cumulative impact of changes in smoking behaviors on
      lung cancer mortality in the United States over the period 1975-2000. METHODS:
      The six groups used common inputs and independent models to estimate the number
      of U.S. lung cancer deaths averted over the period 1975-2000 as a result of
      changes in smoking behavior beginning in the mid fifties, and the number of
      deaths that could have been averted if tobacco control had completely eliminated
      all smoking following issuance of the first SGR on Smoking and Health in 1964.
      RESULTS: Approximately 795,000 deaths (550,000 men and 245,000 women) were
      averted over the period 1975-2000 as a result of changes in smoking behavior
      since in 1950s. In the year 2000 alone approximately 70,000 lung cancer deaths
      were averted (44,000 among men and 26,000 among women). However, these represent
      approximately 30% of lung cancer deaths that could have potentially been averted
      over the period 1975-2000 if smoking was eliminated completely. In the 10-year
      period 1991-2000, this fraction increased to about 37%. CONCLUSIONS: Our results
      show the substantial impact of changes in smoking behavior since the 1950s.
      Despite a major impact of changing smoking behaviors, tobacco control effort are
      still needed to further reduce the burden of this disease.

PMID- 22882890
TI  - Chapter 3: Cohort life tables by smoking status, removing lung cancer as a cause
      of death.
AB  - The purpose of this study was to develop life tables by smoking status removing
      lung cancer as a cause of death. These life tables are inputs to studies that
      compare the effectiveness of lung cancer treatments or interventions, and provide
      a way to quantify time until death from causes other than lung cancer. The study
      combined actuarial and statistical smoothing methods, as well as data from
      multiple sources, to develop separate life tables by smoking status, birth
      cohort, by single year of age, and by sex. For current smokers, separate life
      tables by smoking quintiles were developed based on the average number of
      cigarettes smoked per day by birth cohort. The end product is the creation of six
      non-lung-cancer life tables for males and six tables for females: five current
      smoker quintiles and one for never smokers. Tables for former smokers are linear
      combinations of the appropriate table based on the current smoker quintile before
      quitting smoking and the never smoker probabilities, plus added covariates for
      the smoking quit age and time since quitting.

PMID- 22882891
TI  - Chapter 4: Development of the counterfactual smoking histories used to assess the
      effects of tobacco control.
AB  - Publication of the Surgeon General's Report in 1964 marshaled evidence of the
      harm to public health caused by cigarette smoking, including lung cancer
      mortality, and provided an impetus for introducing control programs. The purpose
      of this article is to develop estimates of their effect on basic smoking exposure
      input parameters related to introduction of the report. Fundamental inputs used
      to generate exposure to cigarettes are initiation and cessation rates for men and
      women, as well as the distribution of the number of cigarettes smoked per day.
      These fundamental quantities are presented for three scenarios: actual tobacco
      control in the United States; no tobacco control in which the experience before
      1955 was assumed to continue; and complete tobacco control in which all smoking
      ceased following publication of the report. These results were derived using data
      from National Health Interview Surveys, and they provide basic input parameters
      for the Smoking History Generator used by each of the lung cancer models
      developed by the Cancer Intervention and Surveillance Modeling Network.

PMID- 22882892
TI  - Chapter 5: Actual and counterfactual smoking prevalence rates in the U.S.
      population via microsimulation.
AB  - The smoking history generator (SHG) developed by the National Cancer Institute
      simulates individual life/smoking histories that serve as inputs for the Cancer
      Intervention and Surveillance Modeling Network (CISNET) lung cancer models. In
      this chapter, we review the SHG inputs, describe its outputs, and outline the
      methodology behind it. As an example, we use the SHG to simulate individual life
      histories for individuals born between 1890 and 1984 for each of the CISNET
      smoking scenarios and use those simulated histories to compute the corresponding
      smoking prevalence over the period 1975-2000.

PMID- 22882893
TI  - Chapter 1:The impact of the reduction in tobacco smoking on U.S. lung cancer
      mortality, 1975-2000: an introduction to the problem.
AB  - To better understand the contribution of cigarette smoking, and its changing role
      in lung cancer, this article provides an introduction to a special issue of Risk
      Analysis, which considers the relationship between smoking and lung cancer death
      rates during the period 1975-2000 for U.S. men and women aged 30-84 years. Six
      models are employed, which are part of a consortium of lung cancer modelers
      funded by National Cancer Institute's Cancer Intervention and Surveillance
      Modeling Network (CISNET). Starting with birth-cohort-specific smoking histories
      derived from National Health Interview Surveys, three scenarios are modeled:
      Actual Tobacco Control (observed trends in smoking), Complete Tobacco Control (a
      counterfactual lower bound on smoking rates that could have been achieved had all
      smoking ceased after the first Surgeon General's report in 1964), and No Tobacco
      Control (a counterfactual upper bound on smoking rates if smoking patterns that
      prevailed before the first studies in the 1950s began to inform the public about
      the hazards of smoking). Using these three scenarios and the lung cancer models,
      the number and percentage of lung cancer deaths averted from 1975-2000, among all
      deaths that could have been averted if tobacco control efforts been immediate and
      perfect, can be estimated. The variability of the results across multiple models
      provides a measure of the robustness of the results to model assumptions and
      structure. The results provide not only a portrait of the achieved impact of
      tobacco control on lung cancer mortality, but also the bounds of what still needs
      to be achieved.

PMID- 22882895
TI  - Chapter 7: Description of MISCAN-lung, the Erasmus MC Lung Cancer microsimulation
      model for evaluating cancer control interventions.
AB  - The MISCAN-lung model was designed to simulate population trends in lung cancer
      (LC) for comprehensive surveillance of the disease, to relate past exposure to
      risk factors to (observed) LC incidence and mortality, and to estimate the impact
      of cancer-control interventions. MISCAN-lung employs the technique of stochastic
      microsimulation of life histories affected by risk factors. It includes the two
      stage clonal expansion model for carcinogenesis and a detailed LC progression
      model; the latter is specifically intended for the evaluation of screenings. This
      article elucidates further the principles of MISCAN-lung and describes its
      application to a comparative study within the CISNET Lung Working Group on the
      impact of tobacco control on U.S. LC mortality. MISCAN-lung yields an estimate of
      the number of LC deaths avoided during 1975-2000. The potential number of
      avoidable LC deaths, had everybody quit smoking in 1965, is 2.2 million; 750,000
      deaths (30%) were avoided in the United States due to actual tobacco control
      interventions. The model fits in the actual tobacco-control scenario, providing
      credibility to the estimates of other scenarios, although considering survey
      reported smoking trends alone has limitations.

PMID- 22882894
TI  - Chapter 6: Lung cancer in never smokers: epidemiology and risk prediction models.
AB  - In this chapter we review the epidemiology of lung cancer incidence and mortality
      among never smokers/nonsmokers and describe the never smoker lung cancer risk
      models used by the Cancer Intervention and Surveillance Network (CISNET)
      modelers. Our review focuses on those influences likely to have measurable
      population impact on never smoker risk, such as secondhand smoke, even though the
      individual-level impact may be small. Occupational exposures may also contribute
      importantly to the population attributable risk of lung cancer. We examine the
      following risk factors in this chapter: age, environmental tobacco smoke, cooking
      fumes, ionizing radiation including radon gas, inherited genetic susceptibility,
      selected occupational exposures, preexisting lung disease, and oncogenic viruses.
      We also compare the prevalence of never smokers between the three CISNET smoking
      scenarios and present the corresponding lung cancer mortality estimates among
      never smokers as predicted by a typical CISNET model.

PMID- 22882896
TI  - Chapter 8: The FHCRC lung cancer model.
AB  - As a member of the Cancer Intervention and Surveillance Modeling Network
      (CISNET), the lung cancer (LC) group at Fred Hutchinson Cancer Research Center
      (FHCRC) developed a model for evaluating U.S. lung cancer mortality trends and
      the impact of changing tobacco consumption. Model components include a
      biologically based two-stage clonal expansion (TSCE) model; a smoking simulator
      to generate smoking histories and other cause mortality; and adjustments for
      period and birth cohort to improve calibration to U.S. LC mortality. The TSCE
      model was first calibrated to five substantial cohorts: British doctors, American
      Cancer Society CPS-I and CPS-II, Health Professionals' Follow-Up Study (HPFS),
      and Nurses' Health Study (NHS). The NHS and HPFS cohorts included the most
      detailed smoking histories and were chosen to represent the effects of smoking on
      U.S. LC mortality. The calibrated TSCE model and smoking simulator were used to
      simulate U.S. LC mortality. Further adjustments were necessary to account for
      unknown factors. This provided excellent fits between simulated and observed U.S.
      LC mortality for ages 30-84 and calendar years 1975-2000. The FHCRC LC model may
      be used to study the effects of public health information on U.S. LC trends and
      the impact of tobacco control policy. For example, we estimated that over 500,000
      males and 200,000 females avoided LC death between 1975 and 2000 due to
      increasing awareness since the mid 1950s of the harmful effects of smoking. We
      estimated that 1.1 million male and 0.6 million female LC deaths were avoidable
      if smokers quit smoking in 1965.

PMID- 22882897
TI  - Synthesis, in vitro biological evaluation and molecular docking studies of
      benzimidamides as potential BACE1 inhibitors.
AB  - A series of 3, 5-disubstituted benzimidamides were synthesized and biologically
      evaluated as potential BACE1 inhibitors. Both the targeted compounds
      (benzimidamides) and the synthetic intermediates (benzonitriles) were tested for
      their BACE1 inhibitory activities in a cell-free FRET assay. All the synthesized
      benzimidamides were active as BACE1 inhibitors and compound 6d showed the lowest
      IC(50) value of 3.35 MUm. Molecular docking study proposed a binding mode, which
      would help to the further optimization on 6d to achieve more potent, BBB
      penetrant BACE1 inhibitors.

PMID- 22882898
TI  - Dating violence victimization across the teen years: abuse frequency, number of
      abusive partners, and age at first occurrence.
AB  - BACKGROUND: Prior longitudinal studies have shown high cumulative dating violence
      exposure rates among U.S adolescents, with 36 percent of males and 44 percent to
      88 percent of females experiencing victimization across adolescence/young
      adulthood. Despite promising information characterizing adolescents' dating
      violence experiences longitudinally, prior studies tended to concentrate on
      physical and sexual types of violence only, and did not report information on the
      number of times dating violence was experienced across multiple abusive partners.
      We used a method similar to the timeline follow-back interview to query
      adolescents about dating violence victimization from age 13 to 19-including
      dating violence types (physical, sexual, and psychological), frequency, age at
      first occurrence, and number of abusive partners. METHODS: A total of 730
      subjects were randomly sampled from university registrar records and invited to
      complete an online survey, which utilized methods similar to the timeline follow
      back interview, to retrospectively assess relationship histories and dating
      violence victimization from age 13 to 19 (eight questions adapted from widely
      used surveys covering physical, sexual, and psychological abuse). Then, for each
      dating violence type, we asked about the number of occurrences, number of abusive
      partners, and age at first occurrence. Of 341 subjects who completed the survey,
      we included 297 (64 percent females; 36 percent males) who had a dating partner
      from age 13 to 19. RESULTS: Fully 64.7 percent of females and 61.7 percent of
      males reported dating violence victimization between age 13 and 19, with most
      experiencing multiple occurrences. More than one-third of abused females had two
      or more abusive partners: controlling behavior (35.6 percent); put downs/name
      calling (37.0); pressured sex (42.9); insults (44.3); slapped/hit (50.0); and
      threats (62.5). Males also had two or more abusive partners, as follows:
      controlling behavior (42.1 percent); insults (51.2); put downs (53.3); threats
      (55.6); and unwanted calls/texts/visits (60.7). Among abused females, 44.7
      percent first experienced controlling behavior between age 13 and 15, whereas the
      majority (62.5 percent) first experienced pressured sex between age 16 and 17.
      Among males, for most abuse types, 16 percent to 30 percent of victimization
      began before age 15. CONCLUSIONS: Our study adds information to a substantial,
      but still growing, body of literature about dating violence frequency, age of
      occurrence, and number of abusive partners among adolescents.

PMID- 22882899
TI  - Proteomic insights into parasite biology.

PMID- 22882900
TI  - N-glycosylation does not affect the catalytic activity of ricin a chain but
      stimulates cytotoxicity by promoting its transport out of the endoplasmic
      reticulum.
AB  - Ricin A chain (RTA) depurinates the alpha-sarcin/ricin loop after it undergoes
      retrograde trafficking to the cytosol. The structural features of RTA involved in
      intracellular transport are not known. To explore this, we fused enhanced green
      fluorescent protein (EGFP) to precursor (preRTA-EGFP), containing a 35-residue
      leader, and mature RTA (matRTA-EGFP). Both were enzymatically active and toxic in
      Saccharomyces cerevisiae. PreRTA-EGFP was localized in the endoplasmic reticulum
      (ER) initially and was subsequently transported to the vacuole, whereas matRTA
      EGFP remained in the cytosol, indicating that ER localization is a prerequisite
      for vacuole transport. When the two glycosylation sites in RTA were mutated, the
      mature form was fully active and toxic, suggesting that the mutations do not
      affect catalytic activity. However, nonglycosylated preRTA-EGFP had reduced
      toxicity, depurination and delayed vacuole transport, indicating that N
      glycosylation affects transport of RTA out of the ER. Point mutations in the C
      terminal hydrophobic region restricted RTA to the ER and eliminated toxicity and
      depurination, indicating that this sequence is critical for ER exit. These
      results demonstrate that N-glycosylation and the C-terminal hydrophobic region
      stimulate the toxicity of RTA by promoting ER export. The timing of depurination
      coincided with the timing of vacuole transport, suggesting that RTA may enter the
      cytosol during vacuole transport.

PMID- 22882901
TI  - A multiparametric assay to compare the cytotoxicity of soy milk with different
      storage media.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the cytotoxicity of soy
      milk compared with several other storage media [coconut water, Hank's Balanced
      Salt Solution (HBSS) and whole milk], assessed through a multiparametric analysis
      employing 3T3 cells. MATERIALS AND METHODS: Plates containing confluent 3T3
      fibroblasts were exposed to the various media for 24 h, at 37 degrees C with 5%
      CO2, and cell viability was evaluated by a multiparametric assay assessing
      sequentially, on the same cells, mitochondrial activity (XTT), membrane integrity
      (neutral red test) and total cell density (crystal violet dye exclusion test).
      Results from each test were compared by two-way analysis of variance (ANOVA).
      RESULTS: Statistical analysis showed that whole milk, HBSS and soy milk were the
      most effective media in maintaining cell viability at all tested times (P <
      0.05). The least amount of viable cells was observed when using coconut water.
      CONCLUSIONS: This study shows that the efficacy of soy milk in maintaining the
      viability of 3T3 fibroblasts is similar to that of HBSS and milk, as shown by
      three different cell viability tests.

PMID- 22882902
TI  - Virus-induced gene-silencing in wheat spikes and grains and its application in
      functional analysis of HMW-GS-encoding genes.
AB  - BACKGROUND: The Barley stripe mosaic virus (BSMV)-based vector has been developed
      and used for gene silencing in barley and wheat seedlings to assess gene
      functions in pathogen- or insect-resistance, but conditions for gene silencing in
      spikes and grains have not been evaluated. In this study, we explored the
      feasibility of using BSMV for gene silencing in wheat spikes or grains. RESULTS:
      Apparent photobleaching on the spikes infected with BSMV:PDS at heading stage was
      observed after 13 days post inoculation (dpi), and persisted until 30 dpi, while
      the spikes inoculated with BSMV:00 remained green during the same period. Grains
      of BSMV:PDS infected spikes also exhibited photobleaching. Molecular analysis
      indicated that photobleached spikes or grains resulted from the reduction of
      endogenous PDS transcript abundances, suggesting that BSMV:PDS was able to induce
      PDS silencing in wheat spikes and grains. Inoculation onto wheat spikes from
      heading to flowering stage was optimal for efficient silencing of PDS in wheat
      spikes. Furthermore, we used the BSMV-based system to reduce the transcript level
      of 1Bx14, a gene encoding for High-molecular-weight glutenin subunit 1Bx14 (HMW
      GS 1Bx14), by 97 % in the grains of the BSMV:1Bx14 infected spikes at 15 dpi,
      compared with that in BSMV:00 infected spikes, and the reduction persisted until
      at least 25 dpi. The amount of the HMW-GS 1Bx14 was also detectably decreased.
      The percentage of glutenin macropolymeric proteins in total proteins was
      significantly reduced in the grains of 1Bx14-silenced plants as compared with
      that in the grains of BSMV:00 infected control plants, indicating that HMW-GS
      1Bx14 is one of major components participating in the formation of glutenin
      macropolymers in wheat grains. CONCLUSION: This is one of the first reports of
      successful application of BSMV-based virus-induced-gene-silencing (VIGS) for gene
      knockdown in wheat spikes and grains and its application in functional analysis
      of the 1Bx14 gene. The established BSMV-VIGS system will be very useful in future
      research on functional analysis of genes contributing to grain quality and the
      metabolic networks in developing seeds of wheat.

PMID- 22882903
TI  - Malaria prevalence among pregnant women in two districts with differing
      endemicity in Chhattisgarh, India.
AB  - BACKGROUND: In India, malaria is not uniformly distributed. Chhattisgarh is a
      highly malarious state where both Plasmodium falciparum and Plasmodium vivax are
      prevalent with a preponderance of P. falciparum. Malaria in pregnancy (MIP),
      especially when caused by P. falciparum, poses substantial risk to the mother and
      foetus by increasing the risk of foetal death, prematurity, low birth weight
      (LBW), and maternal anaemia. These risks vary between areas with stable and
      unstable transmission. The specific objectives of this study were to determine
      the prevalence of malaria, its association with maternal and birth outcomes, and
      use of anti-malarial preventive measures for development of evidence based
      interventions to reduce the burden of MIP. METHODS: A cross-sectional study of
      pregnant women presenting to antenatal clinics (ANC) or delivery units (DU), or
      hospitalized for non-obstetric illness was conducted over 12 months in high
      (Bastar) and low (Rajnandgaon) transmission districts in Chhattisgarh state.
      Intensity of transmission was defined on the basis of slide positivity rates with
      a high proportion due to P. falciparum. In each district, a rural and an urban
      health facility was selected. RESULTS: Prevalence of peripheral parasitaemia was
      low: 1.3% (35/2696) among women at ANCs and 1.9% at DUs (19/1025). Peripheral
      parasitaemia was significantly more common in Bastar (2.8%) than in Rajnandgaon
      (0.1%) (p < 0.0001). On multivariate analysis of ANC participants, residence in
      Bastar district (stable malaria transmission) was strongly associated with
      peripheral parasitaemia (adjusted OR [aOR] 43.4; 95% CI, 5.6-335.2). Additional
      covariates associated with parasitaemia were moderate anaemia (aOR 3.7; 95% CI
      1.8-7.7), fever within the past week (aOR 3.2; 95% CI 1.2-8.6), and lack of
      formal education (aOR 4.6; 95% CI 2.0-10.7). Similarly, analysis of DU
      participants revealed that moderate anaemia (aOR 2.5; 95% CI 1.1-5.4) and fever
      within the past week (aOR 5.8; 95% CI 2.4-13.9) were strongly associated with
      peripheral and/or placental parasitaemia. Malaria-related admissions were more
      frequent among pregnant women in Bastar, the district with greater malaria
      prevalence (51% vs. 11%, p < 0.0001). CONCLUSIONS: Given the overall low
      prevalence of malaria, a strategy of enhanced anti-vector measures coupled with
      intermittent screening and targeted treatment during pregnancy should be
      considered for preventing malaria-associated morbidity in central India.

PMID- 22882904
TI  - Infiltrated cardiac lipids impair myofibroblast-induced healing of the myocardial
      scar post-myocardial infarction.
AB  - OBJECTIVES: Lipids have been detected in the ischemic myocardium of patients'
      post-myocardial infarction (MI). However, their effect on the cardiac healing
      process remains unknown. We investigated whether intramyocardial lipids affect
      the signaling pathways involved in the fibrotic reparative response impairing
      cardiac healing post-MI. METHODS: Pigs, fed either a high-cholesterol diet (HC)
      or a regular-chow (NC), were subjected to experimentally-induced acute MI (90 min
      mid-LAD balloon occlusion) and then, upon reperfusion (R), maintained for 21 days
      with the same diet regime (HC/R(+) and NC/R(+), respectively). A group of
      hypercholesterolemic animals were sacrificed after ischemia without reperfusion
      (HC/R(-)). Cardiac tissue was obtained for molecular/cellular/histological
      analysis. Infarct size and echocardiography were assessed. RESULTS: At the time
      of acute MI, hypercholesterolemic animals showed a higher incidence of
      ventricular dysrhythmias. At sacrifice, intramyocardial lipids were absent in
      HC/R(-). HC/R(+) showed higher lipid content (ApoB, cholesteryl-ester and
      triglycerides) and lower expression/activity of the TGFbeta/TbetaRII/Smad2/3
      pathway (involved in scar reparative fibrosis) than NC/R(+) in the forming scar.
      Collagen synthesis was accordingly reduced in the scar of HC/R(+). Infarct size
      was 44% larger in HC/R(+) which had higher apoptosis and lower Akt/eNOS activity
      in the jeopardized myocardium. Systolic function was similarly deteriorated post
      MI in all animals whereas no changes were detected in diastolic-related
      parameters. No changes were detected in systolic parameters 21 days post-MI in
      NC/R(+) animals. In contrast, both systolic- and diastolic-related parameters
      were further deteriorated in HC/R(+) animals. CONCLUSION: Intramyocardial lipid
      accumulation impairs TGFbeta/TbetaRII/Smad2/3 signaling altering the fibrotic
      reparative process of the scar resulting in larger infarcts and cardiac
      dysfunction.

PMID- 22882905
TI  - Egg yolk consumption and carotid plaque.
AB  - BACKGROUND: Increasingly the potential harm from high cholesterol intake, and
      specifically from egg yolks, is considered insignificant. We therefore assessed
      total plaque area (TPA) in patients attending Canadian vascular prevention
      clinics to determine if the atherosclerosis burden, as a marker of arterial
      damage, was related to egg intake. To provide perspective on the magnitude of the
      effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive
      patients attending vascular prevention clinics at University Hospital had
      baseline measurement of TPA by duplex ultrasound, and filled out questionnaires
      regarding their lifestyle and medications, including pack-years of smoking, and
      the number of egg yolks consumed per week times the number of years consumed (egg
      yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was
      61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with
      age after age 40, but increased exponentially with pack-years of smoking and with
      egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was
      125 +/- 129 mm(2), versus 132 +/- 142 mm(2) in those consuming 3 or more eggs per
      week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression,
      egg-yolk years remained significant after adjusting for coronary risk factors.
      INTERPRETATION: Our findings suggest that regular consumption of egg yolk should
      be avoided by persons at risk of cardiovascular disease. This hypothesis should
      be tested in a prospective study with more detailed information about diet, and
      other possible confounders such as exercise and waist circumference.

PMID- 22882906
TI  - Persistent accumulation of interferon-gamma-producing CD8+CD56+ T cells in blood
      from patients with coronary artery disease.
AB  - OBJECTIVE: There is emerging evidence for CD8(+) T cell alterations in blood from
      patients with coronary artery disease (CAD). We examined whether the distribution
      and phenotype of CD8(+)CD56(+) T cells differed according to the clinical
      manifestation of CAD. METHODS: Patients with acute coronary syndrome (ACS, n =
      30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was
      collected before and up to 12 months after referral for coronary investigation.
      CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface
      markers, apoptosis, and intracellular expression of cytokines. RESULTS: The
      proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA
      patients compared with controls, and remained so after 3 and 12 months. This was
      independent of age, sex, systemic inflammation and cytomegalovirus
      seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in
      terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell
      subsets were positive for interferon (IFN)-gamma and tumor necrosis factor,
      although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells.
      CONCLUSION: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA
      patients share several features with immunological aging. It also contributes to
      a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the
      atherosclerotic process in a less favorable direction.

PMID- 22882907
TI  - Histological validation of iron-oxide and gadolinium based MRI contrast agents in
      experimental atherosclerosis: the do's and don't's.
AB  - MRI using targeted contrast agents (CA) has emerged as a promising technique to
      study atherothrombotic disease in vivo. Particularly, the use of targeted Gd and
      lipid-based nanoparticles has enabled detailed in vivo imaging of various
      molecular markers of atherosclerotic plaque pathophysiology. For validation
      purposes, it is crucial that nanoparticle accumulation in the plaque, cellular
      association and localization can be assessed by ex vivo immuno-histology or
      fluorescence microscopy of tissue sections. In this review we discuss the various
      methods that are available for histological evaluation of targeted MRI contrast
      agents such as lipid-based nanoparticles and iron oxide particles. We discuss the
      detection of these contrast agents in paraffin-embedded and in cryopreserved
      tissue sections of atherosclerotic plaques. During the embedding procedure in
      paraffin, most components of targeted lipid-based nanoparticles are generally
      washed out, though the actual targeting moieties may be retained in the embedded
      sections. Therefore staining of the antibody-antigen complex provides a suitable
      way to visualize the presence of the nanoparticle in the plaque. In cryosections,
      the localization of nanoparticles can be assessed directly by measuring the
      fluorescence of an incorporated fluorophore or by secondary stainings of the Gd
      containing DTPA lipids or the iron oxide particles. With certain secondary
      stainings, be it for the contrast agent or for co-localization with the target,
      the contrast agent itself may interfere with standard histological protocols,
      yielding false positive results. The here presented techniques enable proper
      visualization of MR contrast agent accumulation and localization in
      atherosclerotic plaque, which will provide the validation necessary to advance
      these lipid-based nanoparticles to the clinic.

PMID- 22882908
TI  - The "Sense of Coherence" and the coping capacity of patients with Parkinson
      disease.
AB  - BACKGROUND: Antonovsky's salutogenic model of the "Sense of Coherence" (SOC) is
      an important resource in dealing with chronic diseases. The aim of this study was
      to investigate SOC as a psychological factor and its correlation with illness,
      subjective well-being, and health-related quality of life (QoL) in patients with
      Parkinson disease (PD) compared to patients with other chronic diseases. METHODS:
      Fifty-one patients suffering from PD and 59 participants with other chronic non
      neurological diseases took part in this study. The PD patients were assessed
      through medical routine examinations and all participants were asked to complete
      several questionnaires for psychological assessment. In order to compare controls
      with the PD group, t-tests, U-tests, and multivariate analysis were conducted.
      Multiple regression analysis was calculated to identify predictor variables.
      RESULTS: Patients with PD were characterized by lower SOC and higher scores
      concerning depression compared to the control group (CG). Furthermore, the PD
      group showed fewer active coping strategies and lower scores concerning well
      being. There were correlations between depression, coping, well-being and QoL,
      and SOC. The SOC had a particular predictive value with regards to the outcome
      "quality of life" and coping strategies. CONCLUSIONS: There are a number of
      differences regarding psychological characteristics of coping mechanisms in
      neurological and non-neurological patients. The SOC correlated with several
      psychological factors; however, there was no correlation with medical data. The
      SOC predicts scores pertaining coping mechanism and health-related QoL.

PMID- 22882909
TI  - Rac1 in the driver's seat for melanoma.

PMID- 22882910
TI  - Functional control of the Candida albicans cell wall by catalytic protein kinase
      A subunit Tpk1.
AB  - The cyclic AMP protein kinase A pathway governs numerous biological features of
      the fungal pathogen Candida albicans. The catalytic protein kinase A subunits,
      Tpk1 (orf19.4892) and Tpk2 (orf19.2277), have divergent roles, and most studies
      indicate a more pronounced role for Tpk2. Here we dissect two Tpk1-responsive
      properties: adherence and cell wall integrity. Homozygous tpk1/tpk1 mutants are
      hyperadherent, and a Tpk1 defect enables biofilm formation in the absence of
      Bcr1, a transcriptional regulator of biofilm adhesins. A quantitative gene
      expression-based assay reveals that tpk1/tpk1 and bcr1/bcr1 genotypes show mixed
      epistasis, as expected if Tpk1 and Bcr1 act mainly in distinct pathways.
      Overexpression of individual Tpk1-repressed genes indicates that cell surface
      proteins Als1, Als2, Als4, Csh1 and Csp37 contribute to Tpk1-regulated adherence.
      Tpk1 is also required for cell wall integrity, but has no role in the gene
      expression response to cell wall inhibition by caspofungin. Interestingly,
      increased expression of the adhesin gene ALS2 confers a cell wall defect, as
      manifested in hypersensitivity to the cell wall inhibitor caspofungin and a
      shallow cell wall structure. Our findings indicate that Tpk1 governs C. albicans
      cell wall properties through repression of select cell surface protein genes.

PMID- 22882911
TI  - Clinical characteristics of non-perianal fistulating Crohn's disease in China: a
      single-center experience of 184 cases.
AB  - BACKGROUND: There is little information of non-perianal fistulating Crohn's
      disease in the consensus published by the European Crohn's and Colitis
      Organization in 2006 and 2010. This study was designed to demonstrate the
      clinical characteristics of non-perianal fistulating Crohn's disease among
      homogenous Chinese population. METHODS: One-hundred-and-eighty-four patients were
      retrospectively collected. All of these patients were diagnosed of Crohn's
      disease between February 2001 and April 2011. RESULTS: The male-to-female ratio
      was 2.7:1. The most common symptoms at onset were abdominal pain (88.0%),
      diarrhea (34.7%), and fever (28.3%). The most common disease location and
      behavior at diagnosis were small bowel (56.0%) and penetrating (51.6%). Among 324
      non-perianal fistulae, the most common types were ileocolonic anastomotic
      (30.9%), terminal ileocutaneous (19.7%), and enteroenteric anastomotic (11.4%).
      One-hundred-and-thirty- eight (75.0%) patients received antibiotics, and beta
      lactam (85.5%) and metronidazole (67.4%) are most frequently used. One-hundred
      and-seventy-eight (96.7%) patients suffered 514 surgical operations, and the
      cumulative surgical rates after 1, 3, and 5 years were 38.0%, 52.2%, and 58.7%
      respectively. Nine patients died during the follow-up period, and the cumulative
      survival rates after 1, 3, and 5 years were 97.8%, 96.7%, and 96.2% respectively.
      CONCLUSIONS: This study displayed the clinical characteristics of non-perianal
      fistulating Crohn's disease in our center. Large population-based studies are
      required for further investigation in China.

PMID- 22882912
TI  - Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in
      liver transplantation.
AB  - BACKGROUND: The use of transanastomotic stents for Roux-en-Y hepatojejunostomy
      (RYHJ) in liver transplantation (LT) remains controversial. The aim of this
      retrospective study was to assess the role of transanastomotic stent for RYHJ in
      LT. METHODS: RYHJ for biliary reconstruction in LT was performed in 52 patients.
      Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic
      stents (S group), while 27 patients underwent the same procedure without
      transanastomotic stents (non-S group). The two groups were compared in terms of
      post-LT biliary complications and survival. RESULTS: The incidences of bile
      leakage, anastomotic stricture, non-anastomotic stricture, biliary
      sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5%
      (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0,
      20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group.
      One and three year survival rates were 48.0% (12/25) and 34.0% (8/23),
      respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in
      the non-S group. There was no significant difference between the two groups in
      terms of the incidence of various biliary complications and survival (P > 0.05).
      CONCLUSION: The routine use of transanastomotic stents is not necessary for RYHJ
      for biliary reconstruction in LT.

PMID- 22882913
TI  - Analysis of Gram-positive bacterial infection in patients following liver
      transplantation.
AB  - BACKGROUND: Liver transplantation is the most effective treatment for patients
      with end-stage liver failure, however infection after transplantation is a
      serious clinical complication. The purpose of this research was to investigate
      the molecular epidemiology and the influence of multidrug-resistant Gram-positive
      infection in patients, following liver transplantation, to provide reference for
      clinical treatment and prevention of Gram-positive bacterial infection. METHODS:
      We isolated and detected bacteria from phlegm, throat swabs, urine, wound or
      wound secretions, blood, and fecal samples from 221 liver transplant patients in
      our hospital from January 2007 to April 2010. All isolated bacterial strains were
      identified and tested by minimal inhibitory concentration (MIC) drug-sensitive
      detection using the BioMerieux ATB bacterial identification instrument and
      repetitive extragenic palindromic-polymerase chain reaction (REP-PCR) detection
      of bacterial homology. Risk factors were calculated by multivariate Logistic
      regression analysis. RESULTS: We collected 250 specimens from 221 patients
      hospitalized following liver transplantation surgery, of which 29 patients
      developed multiple infections. Sixty-five Gram-positive bacterial strains were
      isolated from different specimens from 53 infectious patients. We detected 29
      multidrug-resistant Gram-positive strains from 29 patients (44.62%), including 20
      Staphylococcus aureus (S. aureus) strains (68.97%) and nine Enterococcus strains
      (31.03%). All 20 S. aureus strains were highly resistant to aminoglycosides
      (gentamicin), cephalosporins (cefoxitin), quinolones (ciprofloxacin and
      levofloxacin), lincomycins (clindamycin), penicillin, and erythromycin. The
      resistance rate reached 100% in some cases. The S. aureus strains were highly
      sensitive to vancomycin and oxazolidinone (linezolid), with MIC50 < 2 ug/ml for
      both. The nine Enterococci strains were also highly resistant to aminoglycosides,
      quinolones, and penicillins, and highly sensitive to vancomycin (MIC50 < 2 ug/ml)
      and oxazolidinone (MIC50 < 1 ug/ml). Using REP-PCR detection, S. aureus was
      divided into five genotypes with 14 B-type strains. Enterococcus was divided into
      11 genotypes, with two D-type strains, two G-type strains, and two K-type
      strains. The risk factors for Gram-positive bacterial infection in patients
      following liver transplantation were preoperative use of antibiotics (OR = 3.949,
      P = 0.004), high intra-operative blood input (OR = 1.071, P = 0.005), and
      postoperative renal failure (OR = 5.427, P = 0.043). CONCLUSIONS: S. aureus and
      Enterococcus were the main pathogens causing infection following liver
      transplantation in patients with drug-resistant Gram-positive bacterial
      infection. The isolated strains were resistant to multiple antibiotics. B-type S.
      aureus strains were predominant. Reasonable use of antibiotics, decreasing intra
      operative blood input, and preventing post-operative renal failure may reduce
      Gram-positive bacterial infections and the appearance of drug-resistant strains
      following liver transplantation.

PMID- 22882914
TI  - Symptomatic osteonecrosis of the femoral head after adult orthotopic liver
      transplantation.
AB  - BACKGROUND: With the increase of survival in liver transplantation recipients,
      more patients are at a high risk of developing osteonecrosis, especially in the
      femoral head, due to immunosuppressive treatment. The purpose of this study was
      to report the incidence, possible risk factors, and outcome of symptomatic
      osteonecrosis of the femoral head (ONFH) in adult patients with current
      immunosuppressive agents and individual protocol after liver transplantation in
      China. METHODS: A retrospective analysis was performed on 226 adult patients who
      underwent orthotopic liver transplantation (OLT) at a single liver
      transplantation institution between January 2004 and December 2008. The
      posttransplant survival time (or pre-retransplantation survival time) of all the
      patients were more than 24 months. The possible pre- and post-transplantation
      risk factors of symptomatic ONFH were investigated and the curative effects of
      the treatment were also reported. RESULTS: The incidence of ONFH was 1.33% in
      patients after OLT. ONFH occurred at a mean of (14 +/- 6) months (range, 10 - 21
      months) after transplantation. Male patients more often presented with
      osteonecrosis as a complication than female patients. The patients with lower pre
      transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was
      no difference in the cumulative dose of corticosteroids or tacrolimus between the
      patients with or without symptomatic ONFH. Patients were treated either
      pharmacologically or surgically. All patients showed a nice curative effect
      without major complications during the 18 - 63 months post-treatment follow up.
      CONCLUSIONS: The symptomatic ONFH does not occur commonly after adult OLT in the
      current individual immunosuppressive protocol in China.

PMID- 22882915
TI  - Expression of farnesyltransferase in primary liver cancer.
AB  - BACKGROUND: Primary liver cancer (PLC) is a common malignant tumor. Over the past
      decade, although farnesyltransferase (FTase) has emerged as a significant target
      for anticancer therapies and has become a hotspot of cancer research, its exact
      mechanism of action remains unknown. The aim of this study was to investigate the
      expression of FTase in PLC and its role in the development of PLC. METHODS:
      Expression of FTase was detected by real-time fluorescent quantitative-polymerase
      chain reaction (FQ-PCR) in cancer and surrounding normal tissues from 32 patients
      with PLC. RESULTS: Expression of FTase mRNA in PLC was significantly higher than
      that in normal hepatic tissues (P < 0.001). Overexpression of FTase was as high
      as 87.5%. The positive rate for FTase mRNA in the high tendency to metastatic
      recurrence group was obviously higher than that in the low tendency to metastatic
      recurrence group (P = 0.02). The positive rate for FTase mRNA in patients with
      metastatic recurrence during postoperative follow-up was also significantly
      higher than that in those without metastatic recurrence (P = 0.01). CONCLUSIONS:
      The level of FTase mRNA expression in cancer tissues is much higher than in
      normal tissues. FTase may play an important role in the genesis and development
      of PLC and may be one of the reliable markers for the metastatic activity gained
      by liver tumor cells. FTase could be used clinically in predicting metastatic
      recurrence of PLC.

PMID- 22882916
TI  - Randomized controlled trial of antibiotic prophylaxis regimens for transrectal
      ultrasound-guided prostate biopsy.
AB  - BACKGROUND: A prior study showed significant antibiotic resistance to quinolone
      in our population. In this study we aimed to evaluate and compare the efficacy of
      a single versus a combined prophylactic antibiotic regimen before transrectal
      ultrasound-guided prostate biopsy (TRUGPB). METHODS: A prospective randomized
      study was conducted at a university hospital. Patients undergoing TRUGPB were
      randomized into an amoxicillin-clavulanate alone (1 mg; one dose before and two
      doses after biopsy) or an amoxicillin-clavulanate + ciprofloxacin group (250 mg;
      one dose before and two doses after biopsy). Patients were surveyed for infection
      symptoms by phone on days 3 and 30 after TRUGPB. We defined an infective
      complication as the occurrence of symptoms including fever, chills or rigor
      within 30 days after prostate biopsy, requiring medical treatment or
      hospitalization, aided by a territory-wide electronic medical record system.
      RESULTS: Between November 2007 and July 2009, 367 patients were randomized to
      either amoxicillin-clavulanate alone or amoxicillin-clavulanate + ciprofloxacin
      group. The infection rates after TRUGPB were 3.91% in the former group (7 out of
      179 patients) versus 0.53% (1 out of 188 patients) in the latter. Sixty-three
      percent (5/8) of patients with infective complications needed hospitalization.
      There was no intensive care unit admission or mortality during the study period.
      CONCLUSIONS: Combining prophylactic antibiotics with amoxicillin-clavulanate +
      ciprofloxacin significantly reduced the incidence of infective complications
      after TRUGPB. We recommended a combination regimen, especially in centre with
      high incidence of post-TRUGPB infection.

PMID- 22882917
TI  - Influence of clinical characteristics and tumor size on symptoms of bladder
      leiomyoma: a pooled analysis of 61 cases.
AB  - BACKGROUND: Bladder leiomyoma is an uncommon type of bladder neoplasms. Most
      publications are reports of isolated cases. The influence of tumor size on
      patients' early symptoms was seldom analyzed. We aim to investigate the clinical
      characteristics of bladder leiomyoma and the influence of tumor size on
      patients'symptoms in Chinese population. METHODS: We reviewed the medical records
      of eight patients diagnosed with bladder leiomyoma at our department, collected
      53 cases from Chinese National Knowledge Infrastructure (CNKI), Wangfang data
      base, and Chinese Biological Medicine Disk, and performed a pooled analysis. The
      clinical characteristics of the patients were analyzed and then classified into
      symptomatic and asymptomatic groups. The association between tumor size and the
      occurrence of symptoms was evaluated. Furthermore, Logistic regression model was
      constructed to discriminate variables. RESULTS: Women comprised the majority of
      the patients (49/61, 80.3%). The mean age and tumor size were (42.3 +/- 14.0)
      years and (45.0 +/- 25.7) mm, respectively. Among all the symptoms, irritative
      symptoms occurred most frequently (37.7%, 23/61), followed by obstructive urinary
      symptoms (31.1%, 19/61), hematuria (24.6%, 15/61), and abdominal bulge or pain
      (14.8%, 9/61). In our study, patients who were 45 years old or younger tended to
      be asymptomatic compared with elder ones (14/36 vs. 3/25, P = 0.021). The
      histological, as well as anatomical, location of tumor, did not show significant
      differences between symptomatic and asymptomatic patients (P = 0.306 and 0.700).
      Tumors larger than 30 mm in the greatest diameter would cause clinical symptoms
      such as obstructive urinary symptoms (P = 0.048) and irritative symptoms (P =
      0.037). Logistic regression confirmed the association between tumor size and the
      occurrence of symptoms, which was related with age. CONCLUSIONS: Bladder
      leiomyoma occurs mainly in women and most frequently with irritative symptoms.
      The occurrence of symptoms is related to tumor size rather than the location. In
      this setting, patients with endovesical tumors smaller than 30 mm in the greatest
      diameter tended to be asymptomatic, which were usually treated with transurethral
      resection of bladder tumor.

PMID- 22882918
TI  - Neuroelectrophysiological characteristics of Hirayama disease: report of 14
      cases.
AB  - BACKGROUND: Hirayama disease is a juvenile muscular atrophy of the distal upper
      extremities and affects mainly young males. The present study aimed to
      investigate the neuroelectrophysiological characteristics of Hirayama disease.
      METHODS: We retrospectively analyzed the neural conduction velocity (NCV)
      parameters and needle-electrode electromyograms (EMG) of 14 patients with
      Hirayama disease. According to the clinical features of the patients, NCV was
      performed on affected upper-limb including median nerves and ulnar nerves, while
      EMG was selectively performed on upper and lower extremities, sternocleidomast
      and thoracic paraspinal muscles. RESULTS: The median nerves of all affected upper
      limbs of patients with Hirayama disease had normal conduction velocities and
      compound motor action potentials (CMAPs). The ulnar nerves of all affected upper
      limbs also had normal conduction velocities. Of the 16 measured ulnar nerves of
      the affected upper limbs, eight had normal CMAPS, while the other eight showed
      CMAPs below the normal value by < 20%. All patients had neurogenic injury on the
      affected side in muscles innervated by anterior horn cells at the lower cervical
      region (C7-8, T1). Four patients had unilateral upper-limb muscle neurogenic
      injury on the affected side. Seven patients had bilateral upper-limb muscle
      neurogenic injury, while only two patients experienced bilateral upper-limb
      muscle atrophy/weakness. The other three patients showed extensive neurogenic
      injury (unilateral upper-limb muscle atrophy/weakness in one patient, bilateral
      symptoms in the other two patients). CONCLUSIONS: Electromyographic examination
      showed that the majority of Hirayama disease patients exhibited characteristic
      segmental injury in the anterior horn of the lower cervical region, while a few
      patients exhibited extensive neurogenic injury. These data suggest that the
      actual influence of Hirayama disease may be more extensive than indicated by the
      clinical presentations.

PMID- 22882919
TI  - Prospective study of transsphenoidal pituitary surgery: is tumor volume a
      predictor for the residual tumor?
AB  - BACKGROUND: The presence of residual tumor after surgery for pituitary adenoma
      may necessitate further treatment. The suprasellar and parasellar extension of
      the tumor have been widely considered as the predictors for residual tumor.
      However there is scarcity of studies regarding the preoperative tumor volume and
      residual tumor. This study was conducted to evaluate if tumor volume could
      predict the outcome of transsphenoidal pituitary surgery. METHODS: A prospective
      study was designed and 48 patients who underwent transsphenoidal pituitary
      surgery within 1 year in the First Affiliated Hospital of Xi'an Jiaotong
      University were included in this study. The preoperative tumor volume and
      immediate postoperative tumor volume (within 4 - 7 days) were calculated in the
      contrast magnetic resonance imaging by using the formula of ellipsoid. All these
      volumes were divided into three subgroups, i.e. group 1, group 2 and group 3 with
      preoperative volume of less than 4 cm(3), 4 - 8 cm(3), and more than 8 cm(3)
      respectively. The parasellar and suprasellar extension of the tumor were also
      classified by Knosp and modified Hardy's classifications. RESULTS: Baseline
      characteristics were comparable. The preoperative tumor volume of more than 8
      cm(3) (group 3, (12.1 +/- 1.1) cm(3)) had increased risk on postoperative tumor
      residue (P < 0.01) than the other two groups ((2.1 +/- 0.3) cm(3) and (6.1 +/-
      0.3) cm(3) in groups 1 and 2). The mean postoperative volume in group 3 patients
      ((2.2 +/- 0.1) cm(3)) was significantly higher than the other two groups (P <
      0.01). CONCLUSION: Preoperative volume of more than 8 cm(3) can be considered as
      a predictor for postoperative residual volume.

PMID- 22882920
TI  - Effect of in-hospital medical complications on case fatality post-acute ischemic
      stroke: data from the China National Stroke Registry.
AB  - BACKGROUND: In-hospital medical complications are associated with poorer clinical
      outcomes for stroke patients after disease onset. However, few studies from China
      have reported the effect of these complications on the mortality of patients with
      acute ischemic stroke. In this prospective work, the China National Stroke
      Registry Study, we investigated the effect of medical complications on the case
      fatality of patients with acute ischemic stroke. METHODS: From September 2007 to
      August 2008, we prospectively obtained the data of patients with acute stroke
      from 132 clinical centers in China. Medical complications, case fatality and
      other information recorded at baseline, during hospitalisation, and at 3, 6, and
      12 months after stroke onset. Multivariable Logistic regression was performed to
      analyze the effect of medical complications on the case fatality of patients with
      acute ischemic stroke. RESULTS: There were 39 741 patients screened, 14 526
      patients with acute ischemic stroke recruited, and 11 560 ischemic stroke
      patients without missing data identified during the 12-month follow-up. Of the 11
      560 ischemic patients, 15.8% (1826) had in-hospital medical complications. The
      most common complication was pneumonia (1373; 11.9% of patients), followed by
      urinary tract infection and gastrointestinal bleeding. In comparison with
      patients without complications, stroke patients with complications had a
      significantly higher risk of death during their hospitalization, and at 3, 6 and
      12 months post-stroke. Having any one in-hospital medical complication was an
      independent risk factor for death in patients with acute ischemic stroke during
      hospital period (adjusted OR = 6.946; 95%CI 5.181 to 9.314), at 3 months
      (adjusted OR = 3.843; 95%CI 3.221 to 4.584), 6 months (adjusted OR = 3.492; 95%CI
      2.970 to 4.106), and 12 months (adjusted OR = 3.511; 95%CI 3.021 to 4.080).
      Having multiple complications strongly increased the death risk of patients.
      CONCLUSION: Short-term and long-term outcomes of acute stroke patients are
      affected by in-hospital medical complications.

PMID- 22882921
TI  - Serum proteomics of early postoperative cognitive dysfunction in elderly
      patients.
AB  - BACKGROUND: Studies on postoperative cognitive dysfunction (POCD) have attracted
      extensive attention and achieved significant progress. However, the diagnosis of
      POCD is not very satisfactory as no specific biomarkers have been classified. The
      aim of the present study was to evaluate differences in serum protein composition
      between POCD and Non-POCD patients, identify potential biomarkers associated with
      early POCD, and study the mechanism underlying POCD. METHODS: Sixty-eight elderly
      patients (age >= 65 years) received isoflurane inhalation anesthesia for
      arthroplasty surgeries. One day before and seven days after the surgery, these
      patients were subjected to a neuropsychological test and venous blood sample
      collection. Postoperative cognitive dysfunction was determined using Z test
      scores. Based on the results, the patients were divided into POCD and non-POCD
      groups. Twenty-five randomly chosen blood samples obtained seven days after the
      surgery from each group were analyzed on a Bruker ultraFlex(TM) time of flight
      (TOF)/TOF mass spectrophotometer. The resulting peptide fingerprints were
      compared with those from the pre-surgery samples to identify differences in serum
      protein composition. The model designed to distinguish between a non-POCD group
      and a POCD group were established and validated. Three proteins with the most
      significant changes were selected for further characterization. RESULTS: Thirty
      three cases were diagnosed as POCD. Using the Clinprotools software, 58
      polypeptides were found to display differential expression (P < 0.05). Using a
      support vector algorithm method, seven differential peaks were isolated to
      establish a diagnostic model to distinguish POCD patients from normal
      individuals. The prediction rate and recognition rate were 96.89% and 100%,
      respectively. Validation of this model showed that the accuracy rates were 100%
      and 85% using samples from the POCD and non-POCD groups, respectively. Protein
      analysis also led to the identification of fibrinopeptide A (FPA) as a potential
      biomarker for POCD. CONCLUSIONS: Arthroplastic surgery under isoflurane
      inhalation anesthesia causes differential serum protein expression in elderly
      patients. These differentially expressed proteins may contribute to the diagnosis
      of early POCD, which may provide a basis for identifying the underlying mechanism
      of POCD development.

PMID- 22882922
TI  - Value of frozen section examination in diagnosis and treatment of high-grade
      cervical intraepithelial neoplasia.
AB  - BACKGROUND: Invasive cancer of the cervix is considered a preventable disease
      because it has a long pre-invasive state, cervical cytology screening programs
      are currently available, and treatment of pre-invasive lesions is effective. We
      tested the accuracy of frozen section examination (FSE) of cone specimens to
      identify the endocervical margin and rule out invasion in patients with high
      grade cervical intraepithelial neoplasia (CIN). METHODS: For 320 consecutive
      patients with a preoperative biopsy result of CIN stage 2/3, cold-knife
      conization (CKC) was performed followed by FSE. The results from analyses of
      permanent paraffin sections (PS) were compared with the FSE findings. RESULTS:
      The accuracy of FSE was 87% (278/320). For all of the seven patients with an
      invasive squamous cell carcinoma of the cervix identified by FSE, the diagnosis
      was confirmed by PS analysis. For one patient, the FSE result was cervicitis,
      whereas PS analysis showed microinvasive carcinoma. Appropriate surgery was
      performed for all patients based on the FSE and biopsy results. The FSE and PS
      results were not significantly different (P = 0.000). Definitive examination of
      margin status using PS was concordant with FSE findings in all cases.
      CONCLUSIONS: FSE is a rapid and reliable method for evaluating CKC specimens. It
      can identify frank invasion, permit adequate treatment in a one-stage procedure,
      and reliably detect clear resection margins. Since discrepancies do exist and may
      result in inappropriate treatment, further research is required to decrease these
      discrepancies and avoid missing even one case.

PMID- 22882923
TI  - A cross-sectional survey on the prevalence of anxiety symptoms in Chinese
      patients with premature ventricular contractions without structural heart
      disease.
AB  - BACKGROUND: Anxiety appears to be more common in patients with coronary artery
      disease (CHD) than in the general population, and anxiety symptoms may precede
      onset of CHD and play an important role in development of CHD. Little is known
      about the prevalence of anxiety symptoms in Chinese patients with premature
      ventricular contractions (PVCs). Our objective was to study anxiety symptoms and
      potential risk factors in a Chinese population with PVCs but without structural
      heart disease. METHODS: The Zung self-rating anxiety scale (ZSAS) was used to
      assess anxiety symptoms. Correlation between anxiety symptoms and socio
      demographics and medical factors were analyzed by Logistic regression. RESULTS:
      Of 1144 patients with PVCs (487 males and 657 females), age (53 +/- 23) years
      old, disease duration 1 month to 24 years, a total of 381 (33.3%) patients were
      categorized as having anxiety symptoms. Anxiety symptoms increased with age, low
      income, low education level, nationality, PVC count/24 hours, bad social support,
      village settlement type (P < 0.05). Multivariate Logistic regression indicated
      that six variables-education level, ethnic minorities, dwelling place, age, PVC
      count/24 hours, and social support-significantly and independently related with
      anxiety symptoms (P < 0.05). CONCLUSIONS: In the Chinese population, anxiety
      symptoms in subjects with PVCs were frequent. Education level, ethnic minorities,
      dwelling place, age, PVC count/24 hours, and social support were independent risk
      factors for anxiety symptoms. Further research on the relationship between PVCs
      and anxiety symptoms in China is necessary.

PMID- 22882924
TI  - Combined effect of atorvastatin and probucol on plasma cystatin C levels and
      severity of coronary lesion in patients with borderline coronary lesion.
AB  - BACKGROUND: The plasma cystatin C concentration (PcyC) has been demonstrated to
      have prognostic value in acute coronary syndrome, but the study of PcyC in
      patients with borderline coronary lesions is limited. Moreover, the effects of
      atorvastatin and probucol on PcyC and the severity of coronary lesions are
      unknown. This study was to evaluate the effects of the combination of
      atorvastatin and probucol on PcyC and severity of coronary lesion in patients
      with borderline coronary lesions. METHODS: One hundred and thirty consecutive
      patients with borderline coronary lesions (40% to 60% isolated single stenosis
      assessed by quantitative coronary angiography) were enrolled into the borderline
      coronary lesion (BCL) group, and one hundred and thirty-six subjects without
      coronary lesions comprised the controls (CTR). The subjects in the BCL group were
      randomized into routine treatment (RTT, n = 60), and combined treatment with
      atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n
      = 70), both groups were treated for 6 months continuously. The levels of PcyC,
      high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C),
      and triglycerides (TG) were determined. One hundred and four subjects in the BCL
      group were rechecked by coronary angiography. RESULTS: PcyC levels were
      significantly higher in the BCL group than in the CTR group; (2003.26 +/- 825.73)
      ng/ml vs. (1897.83 +/- 664.46) ng/ml (P < 0.01). Compared with patients in the
      RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower
      in the CBT group (P < 0.05). Moreover, there was a trend towards a slight
      decrease in the RTT patients, (54.38 +/- 10.67)% vs. (50.29 +/- 9.89)% (P >
      0.05), and a significant decrease in the CBT patients, (53.65 +/- 9.48%) vs.
      (40.38 +/- 12.93)% (P < 0.05), in the mean percent stenosis of borderline
      coronary lesions before and after six months of treatment. CONCLUSIONS: Cystatin
      C played an important role in the development of coronary artery disease, and was
      associated with the severity of coronary lesions. The combination of atorvastatin
      and probucol decreased PcyC levels, and could be the treatment of choice.

PMID- 22882925
TI  - Gender differences are associated with the clinical features of systemic lupus
      erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) mostly occurred in young women.
      This study was undertaken to investigate the different clinical characteristics
      of SLE between male and female patients, and to identify the sex hormone levels
      and clinical outcomes of different gender in SLE patients. METHODS: Of the 516
      SLE patients admitted to the Peking University People's Hospital from January
      2008 to December 2010, 58 were male and 458 were female. Clinical manifestations,
      laboratory profiles and disease activity scores were evaluated in male and female
      patients. Sex hormones levels were also compared among male patients. RESULTS:
      The median age at SLE onset in male and female patients was 27.2 and 28.6 years,
      respectively. Compared with female patients, at onset of SLE, male patients
      showed higher rates of serious renal disease (58.6% vs. 47.2%, P = 0.064),
      neuropsychiatric SLE (20.7% vs. 12.0%, P = 0.055), and a higher incidence of anti
      ds-DNA (25.9% vs. 16.8%, P = 0.069), anti-Sm (17.2% vs. 8.7%, P = 0.002), anti-Ro
      (46.6% vs. 28.4%, P = 0.004), anti-U1RNP (29.3% vs. 15.3%, P = 0.010),
      anticardiolipin antibody (25.9% vs. 11.4%, P = 0.004), and decreased C3 levels
      (67.2% vs. 49.8%, P = 0.009). Systemic lupus erythematosus disease activity index
      (SLEDAI) scores were higher in men than in women (16.8 vs. 12.8, P = 0.038). Of
      the 58 male patients, 24 had not received aggressive treatment during the three
      months prior to the study. Levels of testosterone and dihydroepiandrosterone
      (DHEA) were lower in male SLE patients than in male healthy controls (P = 0.004
      and P = 0.006, respectively). Low serum testosterone was an independent risk
      factor for the development of lupus nephritis (P = 0.043). Male patients with
      elevated serum prolactin were at increased risk of developing neuropsychiatric
      manifestations of SLE (P = 0.081). CONCLUSION: Early recognition of risk factors
      and appropriate intervention are essential, which might lead to high disease
      activity and serious systemic damage in male SLE patients.

PMID- 22882926
TI  - Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of
      autosomal recessive polycystic kidney disease.
AB  - BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare
      inherited disease, which is a disorder with multiple organ involvement, mainly
      the kidney and liver. It is caused by mutations in the PKHD1 gene. Here, we
      reported the clinical characteristics of a case with ARPKD and analyze the
      genetic features of this patient as well as of his father using targeted exome
      sequencing and Sanger sequencing. METHODS: Genomic DNA was extracted from
      peripheral blood leukocytes obtained from a patient with ARPKD. The mutations
      were identified using exome sequencing and confirmed by Sanger sequencing.
      RESULTS: The patient was diagnosed as ARPKD based on ultrasonography and
      abdominal computed tomography which showed polycystic changes, multiple
      calcinosis of both kidneys, and multiple dilated bile ducts of the liver.
      Compound heterozygous PKHD1 gene mutations A979G and G5935A, which lead to
      substitution of an asparagine for an aspartate at amino acid 327 (N327D) and a
      glycine for an arginine at amino acid 1979 (G1979R) respectively, were identified
      using targeted exome sequencing and confirmed by Sanger sequencing for the
      patient. In addition, the father of the patient was identified to be a carrier of
      heterozygous A979G mutation of this gene. CONCLUSIONS: We identified that the
      compound heterozygous PKHD1 gene mutations are the molecular basis of the patient
      with ARPKD. Targeted exome sequencing is suitable for genetic diagnosis of single
      gene inherited diseases like ARPKD in which the pathogenic gene is a large.

PMID- 22882927
TI  - Pilon fractures: a new classification and therapeutic strategies.
AB  - BACKGROUND: Operative decision-making of Pilon fractures are of great challenges
      until now. The aim of this study was to investigate the guidance of the four
      column theory in decision-making therapeutic strategies for Pilon fractures and
      its result. METHODS: One hundred and ten cases (107 patients) of Pilon fractures
      classified by the four-column theory and treated by ORIF, were reviewed.
      According to the four-column classification scheme, lateral column of 85 cases,
      posterior column of 66 cases, medial column of 77 cases, and anterior column of
      61 cases are involved. Among all the 110 cases, single column of 14 cases, two
      columns of 46 cases, three columns of 17 cases, and all of four columns of 33
      cases are involved. RESULTS: One hundred and eight cases have been followed up.
      The average follow up time is 14.7 months, varying between 7 and 52 months. The
      average healing time is 3.6 months, ranging from 2.5 to 8.0 months. Reduction of
      86.1% reviewed Pilon cases are good or acceptable according to Burwell and
      Charley's Radiology Evaluation System. Ankle function of 87.1% cases are
      excellent or good according to the AOFAS evaluation system. CONCLUSION: As a
      simple and comprehensive classification, the four-column classification can
      contribute to reasonable operation decision-making and good prognosis of Pilon
      fracture.

PMID- 22882928
TI  - Axial and tangential views of the acromioclavicular joint: the introduction of
      new projections.
AB  - BACKGROUND: Routine anteroposterior radiographs of the acromioclavicular (AC)
      joint with or without weight bearing have limitations in demonstrating the AC
      joint. Transarticular fixation with Kirschner wire is a treatment choice for AC
      dislocations. However, percutaneous fixation of the AC joint is technically
      demanding. The C-arm fluoroscopy can be used as routine intraoperative guidance
      to facilitate this procedure. The current study aims to introduce new
      projections, the axial and tangential views of AC joint, to help evaluate the
      severity of the injury and facilitate the percutaneous procedure. METHODS: Three
      shoulder specimens were used to find the projection directions of the axial and
      tangential views of the AC joint by using the digital radiography (DR) unit. The
      axial and tangential views were taken of 20 adult volunteers by referencing the
      projection directions determined in the shoulder specimens. The angles showed on
      the DR system and the angles between the coronal plane of the body and the
      vertical plane of the flat panel detector (FPD) during taking these radiographs
      were recorded. The C-arm fluoroscopy unit was used to take the axial and
      tangential views referencing the angles measured on the DR system. Routine
      anteroposterior radiographs of the AC joint were taken on the volunteers. The
      minimal distances from the distal clavicle to the acromion were measured on both
      tangential and anteroposterior radiographs. The data was statistically analyzed.
      RESULTS: The clear axial and tangential radiographs of AC joints of the
      volunteers were obtained using both DR and C-arm fluoroscopy units. The angles
      demonstrated on the DR window are (20.8 +/- 2.4) degrees  for male and (18.3 +/-
      2.3) degrees  for female. During taking the axial views, the angles between the
      coronal plane of the body and vertical plane of FPD are (23.3 +/- 3.2) degrees 
      for male and (20.1 +/- 2.4) degrees  for female. During taking tangential views,
      the corresponding angles are (117.5 +/- 3.7) degrees  for male and (113.1 +/-
      3.3) degrees  for female. On the tangential radiographs, the minimal distance
      from the distal clavicle to the acromion is (6.1 +/- 1.2) mm, wider than the same
      measurement on the anteroposterior radiographs (P < 0.05). Statistical analyses
      showed no significant differences in the above-mentioned angles and the minimal
      distances between the left and right AC joints (P > 0.05). There were no
      significant differences in the above-mentioned angles between DR and C-arm
      fluoroscopy units (P > 0.05). CONCLUSIONS: The axial and tangential radiographs
      of the AC joint can demonstrate the joint clearly and they can be easily obtained
      with both DR system and C-arm fluoroscopy unit in similar projection directions.

PMID- 22882929
TI  - Clinical attitudes towards pain treatment post-orthopedic surgery: a multicenter
      study in Beijing.
AB  - BACKGROUND: Pain is a common post-operative complication. Incidence of pain
      directly affects patients' quality of life in terms of patient physiology,
      psychology, and social characteristics. This study was to understand clinical
      attitudes with regards to Beijing surgeons, and patients' attitude towards pain
      treatment after orthopedic surgery. METHODS: A hospital-based cross-sectional and
      cluster sample survey of 40 hospitals in Beijing was conducted, including 20
      level III (tier three) and 20 level II (tier two) general hospitals. Enrolled
      subjects completed a specifically designed interview-questionnaire. RESULTS: The
      prevalence of pain 2 weeks post-orthopedic surgery was high in Beijing (96.1%).
      Meanwhile, collected data indicated most subjects in Beijing suffered moderate to
      severe pain, 45.1% and 41.4%, respectively, post-surgery. And for the concern of
      patients before surgery, most subjects chose full recovery from surgery (78.6%),
      as well as, the pain after operation was 39.2% ranked the third. According to the
      data from the study, Tramadol use was more common in Level III hospitals, where
      Somiton was preferred in Level II hospitals. When it came to the education of
      pain before and after operation, more patients get educated before operation than
      after it. In our study, case physicians or attending physicians enacted education
      before and after surgery. Related to the sense of patients, among the surgeons
      preferring post-operative analgesia, 67.6% considered administration when
      receiving complaints of moderate level pain, 50.0% indicated they will terminate
      analgesic treatment once pain degree scale wise decreases to benign pain.
      CONCLUSIONS: The majority of orthopedic patients experience post-operative pain.
      Identification of post-operative pain will facilitate future awareness on pain
      treatment and nursing care in Beijing hospitals, with pain relief through
      regulated improvements in strategic pain management.

PMID- 22882930
TI  - Complications and clinical outcomes of minimally invasive transforaminal lumbar
      interbody fusion for the treatment of one- or two-level degenerative disc
      diseases of the lumbar spine in patients older than 65 years.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)
      has been successfully used to treat degenerative diseases of the lumbar spine.
      There are few reports comparing the complications and clinical outcomes in older
      patients who have undergone one- or two-level MIS-TLIF with those of younger
      patients. The aim of this study was to investigate the clinical outcomes of MIS
      TLIF in the treatment of degenerative disc disease of lumbar spine of the
      patients older than 65 years, with an emphasis on perioperative complications
      compared to the younger patients. METHODS: One hundred and fifty-one consecutive
      cases of one- or two-level degenerative disc disease of lumbar spine treated with
      MIS-TLIF were reviewed for the radiological and clinical outcomes. They were
      divided into elderly group (age >= 65 years old) and younger group (age < 65
      years old), and were followed for at least 6 months. Radiographs were obtained
      before and after surgery, 3 months postoperatively, and at the final follow-up to
      determine the presence of fusion, hardware-related problems. The clinical
      outcomes were evaluated using the Oswestry Disability Index (ODI) before and
      after surgery, and at the final follow-up. The visual analogue scale (VAS) score
      of back and leg pain were evaluated as well. The intra-operative data and peri
      operative complications were recorded. RESULTS: The mean age of these patients at
      operation was (57.7 +/- 14.2) years (range 26 - 82 years). Of 151 patients, 62
      were 65 years or older. The elderly patients had more comorbidities and more
      porportion of lumbar canal stenosis. The overall fusion rate was 88.4% at the
      final follow-up, with no significant difference between younger and elderly
      patients. The ODI, the VAS of back pain and radicular pain of both young and
      elderly group were significantly improved after surgery and at the final follow
      up, without significant difference between two groups. There were 16
      complications with an incidence of 10.6%, including 7 major complications and 9
      minor complications. There was no significant difference of the incidence of
      complications between two groups. The incidence of dura tear was significantly
      related to bilateral deompression. CONCLUSIONS: The clinical and radiological
      outcomes of MIS-TLIF in the treatment of one- or two-level degenerative disc
      diseases of lumbar spine in the elderly patients were satisfactory. Though there
      are more pre-operative comorbidities, with proper patient selection, the elderly
      patients are not at increased risk of perioperative complications compared to
      younger patients. Screw malposition and dura tear, which are the most frequent
      complications, were more related to the surgical technique and should be avoided.

PMID- 22882931
TI  - Does vitamin D affect disease severity in patients with ankylosing spondylitis?
AB  - BACKGROUND: Vitamin D has been found to have a role in the function of the immune
      system. There have been a lot of studies investigating a relation between vitamin
      D and disease activity in ankylosing spondylitis (AS). However, there have not
      been any studies arranging AS in groups according to vitamin D levels and
      determining any differences among these patients in terms of disease activity,
      functional status, quality of life, and other clinical parameters. The aim of
      this study is to compare 25-hydroxy-vitamin D3 (25(OH)D3) levels in AS patients
      with those in normal healthy subjects and to determine the relationship between
      25(OH)D3 levels and AS disease activity, functional status, and quality of life.
      METHODS: Ninety-nine consecutive patients and 42 healthy volunteers were included
      in this study. After a comparison between the patient group and the control
      group, the patient group was divided into normal, insufficient and deficient
      subgroups according to the plasma 25(OH)D3 levels for another comparison.
      RESULTS: The differences in the 25(OH)D3 level between the patient and the
      control groups were statistically insignificant. The number of AS patients whose
      25(OH)D3 levels were classified as normal, insufficient, and deficient were 34,
      29, and 36, respectively. Erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), and Bath AS Disease Activity Index (BASDAI) scores were higher in
      the low (including insufficient and deficient) 25(OH)D3 level subgroups (P <
      0.05). The Bath AS Functional Index (BASFI) and AS Quality of Life (ASQoL) scores
      were significantly different between the normal and the deficient subgroups (P <
      0.05). Pain, BASDAI, ESR, and CRP were inversely correlated to the 25(OH)D3
      levels (P < 0.05). CONCLUSIONS: The plasma 25(OH)D3 levels may decrease in AS
      patients and this may negatively affect disease activity, functional status and
      quality of life.

PMID- 22882932
TI  - Clinical research of comprehensive rehabilitation in treating brachial plexus
      injury patients.
AB  - BACKGROUND: Brachial plexus injury is one of the difficult medical problems in
      the world. The aim of this study was to observe the clinical therapeutic effect
      of comprehensive rehabilitation in treating dysfunction after brachial plexus
      injury. METHODS: Forty-three cases of dysfunction after brachial plexus injury
      were divided into two groups randomly. The treatment group, which totaled 21
      patients (including 14 cases of total brachial plexus injury and seven cases of
      branch brachial plexus injury), was treated with comprehensive rehabilitation
      including transcutaneous electrical nerve stimulation, mid-frequency
      electrotherapy, Tuina therapy, and occupational therapy. The control group, which
      totaled 22 patients (including 16 cases of total brachial plexus injury and six
      cases of branch brachial plexus injury), was treated with home-based electrical
      nerve stimulation and occupational therapy. Each course was of 30 days duration
      and the patients received four courses totally. After four courses, the
      rehabilitation effect was evaluated according to the brachial plexus function
      evaluation standard and electromyogram (EMG) assessment. RESULTS: In the
      treatment group, there was significant difference in the scores of brachial
      plexus function pre- and post-treatment (P < 0.01) in both "total" and "branch"
      injury. The scores of two "total injury" groups had statistical differences (P <
      0.01), while the scores of two "branch injury" groups had statistical differences
      (P < 0.05) after four courses. EMG suggested that the appearance of regeneration
      potentials of the recipient nerves in the treatment group was earlier than the
      control group and had significant differences (P < 0.05). CONCLUSION:
      Comprehensive rehabilitation was more effective in treating dysfunction after
      brachial plexus injury than nonintegrated rehabilitation.

PMID- 22882933
TI  - Positioning study of cervical vertebra pedicle axial line projective point by
      computed tomography image reconstruction.
AB  - BACKGROUND: Safe placement of the screws is a critical aspect of trans-pedicle
      internal fixation, and little information on in vivo morphology of the cervical
      vertebrae pedicle measured with imaging methods is available. The aim of this
      study was to measure the dimensions of cervical vertebrae C3 to C7 and provide
      screw length, screw diameter and tilt angle for clinical cervical vertebra trans
      pedicle internal fixation. METHODS: Thirty Chinese men and women underwent high
      speed spiral computed tomography measurements to obtain data for C3 to C7, and
      the morphology of the cervical vertebra pedicles was reconstructed. RESULTS:
      Reconstructed computer tomography image data revealed that: (1) pedicle sponge
      width increased incrementally from C3 to C7, (2) pedicle depth was similar for C3
      to C7, (3) pedicle angle decreased incrementally from 47.20 degrees  to 33.76
      degrees  for C3 to C7, and (4) pedicle point to midline distance was similar for
      C3 to C7. There were no statistical differences in morphological data between the
      right and the left side. Men had statistically larger values than women for all
      morphological parameters. CONCLUSIONS: Reconstructed computed tomography images
      can provide useful data for clinical cervical vertebra trans-pedicle internal
      fixation. The individual measurement of cervical vertebra pedicles is recommended
      for safe placement of trans-vertebra pedicle screws.

PMID- 22882934
TI  - Fractionated stereotactic radiotherapy with vagina carotica protection technique
      for local residual nasopharyngeal carcinoma after primary radiotherapy.
AB  - BACKGROUND: Local failure of nasopharyngeal carcinoma (NPC) after radiotherapy
      (RT) remains one of the major treatment failures. This study aimed to evaluate
      the clinical efficacy and complications of fractionated stereotactic radiotherapy
      (FSRT) with vagina carotica protection technique for local residual of NPC
      patients after the primary RT. METHODS: From August 2006 to August 2010, FSRT
      with vagina carotica protection technique was applied to 36 patients in our
      department, the patients aged between 13 and 76 years with a median of 41.3
      years, 25 of them were male and 11 were female. According to 2002 Union for
      International Cancer Control (UICC) Staging System, the stages before primary
      radiotherapy were: IIa 2, IIb 5, III 18, IVa 7, IVb 4. In the first course of
      radiotherapy, 9 patients received conventional RT, 27 patients received intensity
      modulated radiotherapy (IMRT) and 20 out of the 36 patients received concurrent
      chemoradiotherapy. The total dose in the first course of RT was 69.96 - 76.90 Gy
      (median, 72.58 Gy). The intervals between the primary RT and FSRT ranged from 12
      to 147 days (median, 39.8 days). Target volumes ranged from 1.46 to 32.98 cm(3)
      (median, 14.94 cm(3)). The total FSRT doses were 10.0 - 24.0 Gy (median, 16.5 Gy)
      with 2.0 - 5.0 Gy per fraction. The most common regimen was 15 Gy in 5 fractions
      of 3 Gy, the irradiation dose to vagina carotica was less than 2 Gy per fraction.
      RESULTS: The median follow-up time was 34 months (range, 12 - 59 months). The 3
      year local control rate was 100%; the 3-year overall survival rate was 94.4%; the
      3-year disease-free survival rate was 77.8%. In this study, we had one case of
      cranial nerve injury, two cases of temporal lobe necrosis, and no nasopharyngeal
      massive hemorrhage was observed. CONCLUSION: FSRT with vagina carotica protection
      technique is an effective and safe RT regimen for local residual of NPC with
      reduction of radiation-related neurovascular lesions.

PMID- 22882935
TI  - Immature CD4+ dendritic cells conditioned with donor kidney antigen prolong renal
      allograft survival in rats.
AB  - BACKGROUND: Allogeneic transplant rejection is currently a major problem
      encountered during organ transplantation. The dendritic cell (DC) is the most
      effective powerful known professional antigen-presenting cell, and recent studies
      have found that DCs can also induce immune tolerance, and avoid or reduce the
      degree of transplant rejection. The aim of this study was to evaluate the effect
      of transfused immature CD4(+) DCs on renal allografts in the rat model. METHODS:
      In this study, we induced CD4(+) immature DCs from rat bone marrow cells by a
      cytokine cocktail. The immature CD4(+) DCs were identified by morphological
      analysis and then the suppressive activity of these cells conditioned with donor
      kidney antigen was evaluated in vitro and in vivo. RESULTS: Immature CD4(+) DCs
      conditioned with donor kidney antigen possessed immunosuppressive activity in
      vitro and they were able to prolong renal transplant survival in an allograft rat
      model in vivo. CONCLUSIONS: Our study provides new information on efficacious
      renal transplantation, which might be useful for understanding the function of
      immature CD4(+) DCs in modulating renal transplant rejection and improving
      clinical outcome in future studies.

PMID- 22882936
TI  - Pre-clinical evaluation of a new indirectly labeled 99mTc-6-hydrazinopyridine-3
      carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator.
AB  - BACKGROUND: Technetium-99m or (99m)Tc is widely used for labeling peptide in
      nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after
      binding with its receptor. This research was to study the preclinical effect of a
      new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect
      (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator. METHODS:
      The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide,
      and [ClCH(2)-CO*b-Dap-Lys- Cys-Lys*amide] were synthesized by Fmoc solid-phase
      synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase
      synthesis. The product depreotide was isolated and purified by high performance
      liquid chromatography and was confirmed by mass spectrography. Depreotide was
      labeled with (99m)Tc through a direct labeling method, using HYNIC as a
      bifunctional chelator. Paper chromatography method was used to calculate the
      labeling rate, and through the comparative analysis selected the best mark
      conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance
      liquid chromatography (HPLC). The internalization and externalization rates of
      the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore,
      biodistribution of the radiopeptide was studied in nude mice, bearing tumors from
      human lung carcinoma cells SPC-A1. RESULTS: The molecular of synthesize
      depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of
      (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15 degrees C, about (70.95 +/-
      0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of
      (20.75 +/- 0.48)% at 60 minutes in A549 cells at 37 degrees C and decreased
      slightly later, while it elevated gradually during the time course at 4 degrees C
      and 25 degrees C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at
      37 degrees C increased gradually and reached the peak of 84.4% in 120 minutes,
      while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always
      less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc
      HYNIC-depreotide demonstrated a high tumor uptake of (4.05 +/- 0.04)% ID/g at 1.5
      hpi and remained high ((2.51 +/- 0.06)% ID/g) at 4 hpi. The tumor-to-lung
      activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC
      depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and
      tumor-to-blood activity concentration ratios (T/Bl). CONCLUSION: The findings
      suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate
      radiopharmaceutical for imaging somatostatin receptor positive lung cancer.

PMID- 22882937
TI  - Therapeutic effect of an injectable sustained-release sinomenine hydrochloride
      and sodium hyaluronate compound in a rabbit model of osteoarthritis.
AB  - BACKGROUND: While intra-articular injection of sinomenine hydrochloride has a
      therapeutic effect on osteoarthritis, it has a short half-life, and is
      thermolabile and photolabile. The aim of this research was to evaluate the
      sustained-release of sinomenine hydrochloride from an injectable sinomenine
      hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect
      in a rabbit model of osteoarthritis following intra-articular injection. METHODS:
      An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine
      hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine
      hydrochloride was prepared and kept as the control group. The cumulative mass
      release was measured at different time points in each group in vitro. Sixty-five
      male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each
      for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups
      respectively, and five (10 knees) for the modeling group. Papain was injected
      into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of
      the corresponding drugs was injected into the articular cavities of the remaining
      experiment groups, while the control group was treated with 0.2 ml normal saline.
      All groups were treated once a week for 4 weeks. Seven days after the last
      treatment, knees were anatomized to perform pathological observations and
      Mankin's evaluation of the synovium. Four groups were compared using the SPSS
      13.0 software package. RESULTS: In the in vitro sustained-release experiments,
      90% of the drug was released in the experiment group 360 minutes following the
      injection. Comparison of the Mankin's evaluations of the four groups illustrated
      statistical discrepancies (P < 0.05). In further paired comparisons of the CSSSI
      group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups,
      statistical significance was uniformly obtained. Moreover, sodium hyaluronate and
      sinomenine hydrochloride treatments showed significant improvement over the
      modeling control (P < 0.05), whereas sodium hyaluronate vs. sinomenine
      hydrochloride comparison failed to reach significance (P > 0.05). CONCLUSIONS:
      CSSSI has a sustained-release effect on sinomenine hydrochloride. Intra-articular
      injection of CSSSI was significantly better than the sole sodium hyaluronate or
      sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.

PMID- 22882938
TI  - Molecular mechanisms of diabetic coronary dysfunction due to large conductance
      Ca2+-activated K+ channel impairment.
AB  - BACKGROUND: Diabetes mellitus is associated with coronary dysfunction,
      contributing to a 2- to 4-fold increase in the risk of coronary heart diseases.
      The mechanisms by which diabetes induces vasculopathy involve endothelial
      dependent and -independent vascular dysfunction in both type 1 and type 2
      diabetes mellitus. The purpose of this study is to determine the role of vascular
      large conductance Ca(2+)-activated K(+) (BK) channel activities in coronary
      dysfunction in streptozotocin-induced diabetic rats. METHODS: Using
      videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we
      investigated the coronary BK channel activities and BK channel-mediated coronary
      vasoreactivity in streptozotocin-induced diabetic rats. RESULTS: BK currents
      (defined as the iberiotoxin-sensitive K(+) component) contribute (65 +/- 4)% of
      the total K(+) currents in freshly isolated coronary smooth muscle cells and >
      50% of the contraction of the inner diameter of coronary arteries from normal
      rats. However, BK current density is remarkably reduced in coronary smooth muscle
      cells of streptozotocin-induced diabetic rats, leading to an increase in coronary
      artery tension. BK channel activity in response to free Ca(2+) is impaired in
      diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel
      b(1) subunit activator) robustly enhanced the open probability of BK channels in
      coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect
      was diminished in the presence of 200 nmol/L Ca(2+) and was significantly
      attenuated in the presence of high free calcium concentration, i.e., 1 mmol/L
      Ca(2+). Immunoblotting experiments confirmed that there was a 2-fold decrease in
      BK-b(1) protein expression in diabetic vessels, without altering the BK channel
      alpha-subunit expression. Although the cytosolic Ca(2+) concentration of coronary
      arterial smooth muscle cells was increased from (103 +/- 23) nmol/L (n = 5) of
      control rats to (193 +/- 22) nmol/L (n = 6, P < 0.05) of STZ-induced diabetic
      rats, reduced BK-b(1) expression made these channels less sensitive to
      intracellular Ca(2+), which in turn led to enhanced smooth muscle contraction.
      CONCLUSIONS: Our results indicated that BK channels are the key determinant of
      coronary arterial tone. Impaired BK channel function in diabetes mellitus is
      associated with down-regulation of BK-b(1) expression and reduction of the b(1)
      mediated BK channel activation in diabetic vessels.

PMID- 22882939
TI  - Expression and significance of myeloid differentiation factor 88 in marrow
      dendritic cells in asthmatic rats with cigarette smoke exposure.
AB  - BACKGROUND: Smoking causes frequent asthma attacks, leading to a rapid decline in
      lung function in patients with asthma, and it can also reduce the therapeutic
      effect of glucocorticoids in patients with asthma. Therefore, the present study
      aimed to investigate the effect of cigarette smoke on the expression of myeloid
      differentiation factor 88 (MyD88) in marrow dendritic cells (DCs) in asthmatic
      rats, and to explore the molecular mechanism of cigarette smoke exposure on
      asthma by DCs. METHODS: Forty Wistar rats were randomly divided into the
      following groups: control, smoke exposure, asthma, and asthma combined with smoke
      exposure. The animal model was established, and then rat bone marrow-derived DCs
      were collected. Additionally, rat spleen lymphocytes and bone marrow-derived DCs
      were cultured together for mixed lymphocyte responses. Interferon (IFN)-gamma and
      interleukin (IL)-4, IL-10, and IL-12 expressions were determined by enzyme-linked
      immunosorbent assay (ELISA). MyD88 expression was determined by Western blotting.
      The proliferation of lymphocytes was examined with methyl thiazolyl tetrazolium
      (MTT) colorimetric assay. RESULTS: MyD88 expression was decreased in the asthma
      combined with smoke exposure group compared to the asthma group (P < 0.01), and
      IL-10 and IL-12 expressions were decreased in the asthma combined with smoke
      exposure group compared to control group (P < 0.01). In addition, DCs stimulating
      activity on allogeneic lymphocytes were significantly decreased in the smoke
      exposure combined with asthma group compared to the control and asthma groups (P
      < 0.01). After allogeneic mixed lymphocyte responses, IL-4 expression was
      increased and IFN-gamma was decreased in the asthma group and the asthma combined
      with smoke exposure group compared to control group (P < 0.01). IL-4 expression
      was increased and IFN-gamma was decreased in the asthma combined with smoke
      exposure group compared to the asthma group (P < 0.01). The study also showed
      that MyD88 expression was positively correlated with IL-12 and IFN-gamma
      expressions and the activity of lymphocytes (P < 0.01), and negatively correlated
      with IL-4 expression (P < 0.01). CONCLUSIONS: Smoking aggravates asthma by
      weankening immunological mechanism. MyD88-dependent pathways may play a role in
      the immunological balance and activation of lymphocytes.

PMID- 22882940
TI  - In vivo administration of Fms-like tyrosine kinase-3 ligand effectively
      stimulates lung dendritic cell expansion in mice.
AB  - BACKGROUND: Dendritic cells (DCs) are the most important professional antigen
      presenting cells that play a key role in initiating adaptive immune responses.
      The depletion and dysfunction of DCs contribute to the development of
      immunodeficiency or immunoparalysis in some lung diseases. In the present study,
      we investigated the effects of Fms-like tyrosine kinase-3 ligand (Flt3L)
      administration in vivo on lung DCs expansion to provide an experimental basis of
      Flt3L used as a potential therapeutic agent for the related lung disorders.
      METHODS: Balb/c mice were randomly divided into Flt3L group (n = 10) and control
      group (n = 10). Each mouse in the Flt3L group received subcutaneous
      administration of Flt3L at a dose of 10 ug once daily for nine consecutive days.
      Lung histology was observed, and CD11c and CD205 were immunologically labeled in
      lung tissue sections. Low-density lung cells were separated by density gradient
      centrifugation, and then subsets and MHC-II/I-A(d) expression of DCs were
      analyzed by flow cytometry. RESULTS: In the Flt3L group the number and density of
      DC-like cells were markedly increased compared with the control group, mainly
      distributed in the alveolar septa. Immunological labeling in situ found that
      there were significantly higher numbers of CD11c(+) and CD205(+) DCs in lung
      mesenchymal tissue (P < 0.05), where they formed a denser reticular formation.
      Flow cytometry analysis demonstrated that the proportions of myeloid
      CD11c(+)CD11b(+) DCs and plasmacytoid CD11c(+)CD45R/B220(+) DCs in the low
      density lung cells in the Flt3L group were significantly higher compared with the
      control group; showing 3.17- and 3.3-fold increase respectively (P < 0.05). The
      proportion of CD11c(+) DCs expressing MHC-II/I-A(d+) was significantly increased,
      with a 2.7-fold increase as compared with the control group (P < 0.05).
      CONCLUSIONS: Flt3L administration in vivo induces lung DCs expansion, favoring
      myeloid and plasmacytoid DC subsets, which are phenotypically more mature. Flt3L
      may be useful in the therapy to augment immune function of the lung.

PMID- 22882941
TI  - Effects of tensile forces on serum deprivation-induced osteoblast apoptosis:
      expression analysis of caspases, Bcl-2, and Bax.
AB  - BACKGROUND: Apoptosis is involved in the adaptive responses of bone to mechanical
      loading. The purpose of this study was to investigate the effects of tensile
      forces on osteoblast apoptosis and the related mechanism by analyzing the
      expression of caspases, Bcl-2, and Bax. METHODS: Primary osteoblasts were
      harvested from neonatal rat calvaria and were subjected to cyclic tensile forces
      for 72 hours using Flexcell 4000 strain unit in Minimum Essential Medium (MEM)
      with 10% fetal calf serum (FCS) or with serum deprivation. Apoptosis was tested
      by flow cytometry using annexin V/PI staining. Caspase-3 activity was analyzed
      via Elisa. The gene expression of caspase-8, -9, Bcl-2, and Bax was quantified by
      reverse transcription (RT)-PCR. RESULTS: In 10% FCS condition, no significant
      difference in cell apoptosis was found between the stretched and non-stretched
      osteoblast cultures. Serum withdrawal resulted in higher apoptosis rate in the
      osteoblasts with increased caspase-3 activity, and elevated expression of caspase
      9 and Bax. Six-percent elongation of stretch attenuated the cell apoptosis
      induced by serum starvation, concurrent with a decrease in caspase-3 activity, a
      decline of caspase-8 expression, and an elevation of Bcl-2 level. On the
      contrary, 12% elongation of stretch increased caspase-3 activity and promoted the
      apoptosis with an elevated expression of caspase-8 and Bax. No significant change
      of caspase-9 expression was identified upon force application. CONCLUSIONS: These
      results suggested that tensile forces regulate cell apoptosis of primary rat
      osteoblasts through caspase-3 and caspase-8 signaling cascade. Light forces
      rescue the cells from serum deprivation-induced apoptosis by elevating Bcl-2
      expression, while heavy forces promote the apoptotic insult by inducing Bax
      expression.

PMID- 22882942
TI  - Normal age-related viscoelastic properties of chondrons and chondrocytes isolated
      from rabbit knee.
AB  - BACKGROUND: The mechanical microenvironment of the chondrocytes plays an
      important role in cartilage homeostasis and in the health of the joint. The
      pericellular matrix, cellular membrane of the chondrocytes, and their
      cytoskeletal structures are key elements in the mechanical environment. The aims
      of this study are to measure the viscoelastic properties of isolated chondrons
      and chondrocytes from rabbit knee cartilage using micropipette aspiration and to
      determine the effect of aging on these properties. METHODS: Three age groups of
      rabbit knees were evaluated: (1) young (2 months, n = 10); (2) adult (8 months, n
      = 10); and (3) old (31 months, n = 10). Chondrocytes were isolated from the right
      knee cartilage and chondrons were isolated from left knees using enzymatic
      methods. Micropipette aspiration combined with a standard linear viscoelastic
      solid model was used to quantify changes in the viscoelastic properties of
      chondrons and chondrocytes within 2 hours of isolation. The morphology and
      structure of isolated chondrons were evaluated by optical microscope using
      hematoxylin and eosin staining and collagen-6 immunofluorescence staining.
      RESULTS: In response to an applied constant 0.3 - 0.4 kPa of negative pressure,
      all chondrocytes exhibited standard linear viscoelastic solid properties. Model
      predictions of the creep data showed that the average equilibrium modulus
      (E(infinity)), instantaneous modulus (E(0)), and apparent viscosity (m) of old
      chondrocytes was significantly lower than the young and adult chondrocytes (P <
      0.001); however, no difference was found between young and adult chondrocytes (P
      > 0.05). The adult and old chondrons generally possessed a thicker pericellular
      matrix (PCM) with more enclosed cells. The young and adult chondrons exhibited
      the same viscoelastic creep behavior under a greater applied pressure (1.0 - 1.1
      kPa) without the deformation seen in the old chondrons. The viscoelastic
      properties (E(infinity), E(0), and m) of young and adult chondrons were
      significantly greater than that observed in young and adult cells, respectively
      (P < 0.001). The adult chondrons were stiffer than the young chondrons under
      micropipette aspiration (P < 0.001). CONCLUSIONS: Our findings provide a
      theoretical model to measure the viscoelastic properties of the chondrons as a
      whole unit by micropipette aspiration, and further suggest that the properties of
      the chondrocytes and PCM have an important influence on the biomechanical
      microenvironment of the knee joint cartilage degeneration that occurs with aging.

PMID- 22882943
TI  - Thymidylate synthase genetic polymorphisms and cancer risk: a meta-analysis of 37
      case-control studies.
AB  - BACKGROUND: Several studies have evaluated the association between polymorphisms
      of thymidylate synthase (TS) and cancer risk in diverse populations but with
      conflicting results. By pooling the relatively small samples in each study, it is
      possible to evaluate the association using a meta-analysis. METHODS: A
      comprehensive search was conducted to identify all case-control studies on TS on
      a 28-bp tandem repeats in 5'untranslated region (5'UTR) and a 6-bp insertion
      (ins) and deletion (del) mutation in 3'UTR of the gene and cancer risk. Meta
      analysis was conducted using a fixed and random effect model. RESULTS: Our meta
      analysis on a total of 13 307 cancer cases and 18 226 control subjects from 37
      published case-control studies showed no significant association between the risk
      of cancer and the 5'UTR 28-bp tandem repeats polymorphism (3R/3R vs. 2R/2R: OR =
      1.06, 95%CI, 0.93 - 1.20) or the 3'UTR 6-bp ins/del polymorphism (del6/del6 vs.
      ins6/ins6: OR = 0.93, 95%CI, 0.81 - 1.08) with significant between-study
      heterogeneity. In the cancer type- and ethnic subgroup-stratification analyses,
      we did not find any association between TS polymorphisms and cancer risk either.
      CONCLUSION: TS 5'UTR 28-bp tandem repeats and 3'UTR 6-bp ins/del polymorphisms
      may not be associated with cancer risk.

PMID- 22882944
TI  - Association of estrogen receptor alpha gene polymorphisms with bone mineral
      density: a meta-analysis.
AB  - BACKGROUND: A number of studies have examined the association between estrogen
      receptor alpha (ESR-alpha) gene polymorphisms and bone mineral density (BMD), but
      previous studies of ESR-alpha gene XbaI (rs9340799) and PvuII (rs2234693)
      polymorphisms have been hampered by small sample size, regional restrictions and
      inconclusive results. Thus a meta-analysis is needed to assess their pooled
      effects. METHODS: This study reviewed all published articles indexed in Pubmed
      using the keywords in the title or abstract. All data were extracted
      independently by two reviewers using a standard form, the studies were meta
      analyzed and minor discrepancies were resolved by authors' discussion. RESULTS:
      Twenty seven eligible studies involving 8467 women and 2032 men were identified.
      The XbaI and PvuII polymorphisms were significantly associated with BMD of the
      lumbar spine. XX and PP homozygotes had a protective effect in comparison with
      carriers of the x and p alleles, the effects were more significant in
      premenopausal women or Western women. At the femoral neck, the results were
      different. XX served as a protective factor in postmenopausal women, Western
      women, Western postmenopausal women, and men, while PP was likely to serve as a
      risk factor in Eastern women, Eastern postmenopausal women, and men. CONCLUSIONS:
      The XbaI polymorphism is correlated to BMD at diverse skeletal sites. PP had a
      protective role for the lumbar spine but might be a risk factor for the femoral
      neck.

PMID- 22882946
TI  - The concentration of platelet microparticles is increased in old patients with
      essential hypertension complicating with coronary heart disease.

PMID- 22882945
TI  - Role of reactive oxygen species in the renal fibrosis.
AB  - Renal fibrosis is a common pathway of progressive renal diseases leading to end
      stage renal disease regardless of the etiology. Accumulating evidence indicates
      that oxidative stress, resulting in generation of reactive oxygen species (ROS),
      plays a critical role in the initiation and progression of fibrotic diseases.
      Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant
      enzyme source for ROS generation and is now recognized as a key mediator of cell
      proliferation and matrix accumulation in renal disease. Multiple stimuli and
      agonists, such as transforming growth factor beta1, tumor necrosis factor,
      platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low
      density lipoprotein and albumin have been shown to alter the activity or
      expression of the NADPH oxidase and ultimately increase ROS production. ROS
      directly incites damage to biologically important macromolecules and leads to
      generation of the so-called advanced oxidation protein products (AOPPs) and
      advanced glycation end products, which are not only markers of oxidative stress
      but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs
      production might be a novel strategy for the therapeutic intervention of variety
      of fibrotic kidney disorders.

PMID- 22882947
TI  - Application of systems biology to the study of chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a major public health problem that affects about
      10% of the general population. Current approaches to characterize the category
      and progression of CKD are normally based on renal histopathological results and
      clinical parameters. However, this information is not sufficient to predict CKD
      progression risk reliably or to guide preventive interventions. Nowadays, the
      appearance of systems biology has brought forward the concepts of "-omics"
      technologies, including genomics, transcriptomics, proteomics, and metabolomics.
      Systems biology, together with molecular analysis approaches such as microarray
      analysis, genome-wide association studies (GWAS), and serial analysis of gene
      expression (SAGE), has provided the framework for a comprehensive analysis of
      renal disease and serves as a starting point for generating novel molecular
      diagnostic tools for use in nephrology. In particular, analysis of urinary mRNA
      and protein levels is rapidly evolving as a non-invasive approach for CKD
      monitoring. All these systems biological molecular approaches are required for
      application of the concept of "personalized medicine" to progressive CKD, which
      will result in tailoring therapy for each patient, in contrast to the "one-size
      fits-all" therapies currently in use.

PMID- 22882948
TI  - Cognitive deficits in patients with brain tumor.
AB  - OBJECTIVE: To discuss the present status and progress of clinical research on the
      cognitive effects caused by different types of brain tumors and common
      treatments. DATA SOURCES: The data used in this review were mainly from PubMed
      articles published in English from 1990 to Febuary 2012. Research terms were
      "cognitive deficits" or "cognitive dysfunction". STUDY SELECTION: Articals
      including any information about brain tumor related cognitive deficits were
      selected. RESULTS: It is widely accepted that brain tumors and related treatments
      can impair cognitive function across many domains, and can impact on patients'
      quality of life. Tumor localization, lateralization, surgery, drugs, radiotherapy
      and chemotherapy are all thought to be important factors in this process.
      However, some conflicting findings regarding brain tumor-related cognitive
      deficits have been reported. It can be difficult to determine the mechanism of
      these treatments, such as chemotherapy, antibiotics, antiepileptics, and
      steroids. Future research is needed to clarify these potential treatment effects.
      CONCLUSIONS: Cognitive function is important for patients with brain tumor. Much
      more focus has been paid on this field. It should be regarded as an important
      prognostic index for the patients with brain tumor, and neuropsychological tests
      should be used in regular examinations.

PMID- 22882949
TI  - Rhabdomyosarcoma of the breast: a clinicopathologic study and review of the
      literature.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is an uncommon malignancy of the breast. The
      aim of this study was to summarize its clinicopathologic features and biological
      behavior. METHODS: Five primary or secondary breast RMSs were collected. Their
      clinicopathological characteristics and all published literature about breast RMS
      were reviewed. Immunohistochemical study of desmin, myogenic differentiation 1
      (MyoD1), myogenin, leukocyte common antigen (LCA), vimentin, cytokeratin
      (AE1/AE3), E-cadherin, neuron specific enolase (NSE), CD99, chorioallantoic
      membrane 5.2 (CAM5.2) and epithelial membrane antigen (EMA) expression were
      performed. RESULTS: The five patients were all female with ages ranging from 16
      to 46 years old (mean, 30 years). Three were metastatic breast RMSs, two
      embryonal and one solid variant alveolar, with the primary tumor sites the right
      labium majus, left nasal meatus and nasopharynx, respectively. The other two, one
      embryonal and one alveolar, were primaries. Grossly, the surgical specimens
      revealed round or oval, well-demarcated but nonencapsulated masses. Their cut
      surfaces consisted of homogeneous grayish yellow or white tissue.
      Microscopically, most tumor cells were poorly differentiated small round, oval or
      small polygons with eosinophilic cytoplasm. All cases were positive for vimentin,
      desmin, MyoD1 and myogenin. One embryonal RMS also had a few cells with
      perinuclear staining of AE1/AE3. The other markers were negative. CONCLUSIONS:
      Although primary or metastatic RMS in breast was almost confined to young
      adolescent females, our cases suggested that it can also happen to the middle
      aged women. Embryonal RMS has a certain metastatic potential. MyoD1 and myogenin
      are two useful markers when making differential diagnosis. Axillary lymph node
      status and age may play a role in the prognosis of primary breast RMS patients.

PMID- 22882950
TI  - Outcome and risk factors of early onset severe preeclampsia.
AB  - BACKGROUND: Early onset severe preeclampsia is a specific type of severe
      preeclampsia, which causes high morbidity and mortality of both mothers and
      fetus. This study aimed to investigate the clinical definition, features,
      treatment, outcome and risk factors of early onset severe preeclampsia in Chinese
      women. METHODS: Four hundred and thirteen women with severe preeclampsia from
      June 2006 to June 2009 were divided into three groups according to the
      gestational age at the onset of preeclampsia as follows: group A (less than 32
      weeks, 73 cases), group B (between 32 and 34 weeks, 71 cases), and group C
      (greater than 34 weeks, 269 cases). The demographic characteristics of the
      subjects, complications, delivery modes and outcome of pregnancy were analyzed
      retrospectively. RESULTS: The systolic blood pressure at admission and the
      incidence of severe complications were significantly lower in group C than those
      in groups A and B, prolonged gestational weeks and days of hospitalization were
      significantly shorter in group C than those in groups A and B. Liver and kidney
      dysfunction, pleural and peritoneal effusion, placental abruption and postpartum
      hemorrhage were more likely to occur in group A compared with the other two
      groups. Twenty-four-hour urine protein levels at admission, intrauterine fetal
      death and days of hospitalization were risk factors that affected complications
      of severe preeclampsia. Gestational week at admission and delivery week were also
      risk factors that affected perinatal outcome. CONCLUSIONS: Early onset severe
      preeclampsia should be defined as occurring before 34 weeks, and it is featured
      by more maternal complications and a worse perinatal prognosis compared with that
      defined as occurring after 34 weeks. Independent risk factors should be used to
      tailor the optimized individual treatment plan, to balance both maternal and
      neonatal safety.

PMID- 22882951
TI  - Fungal infection after a tragedy: a report of three cases of candidosis in a fire
      accident.
AB  - Patients who suffer severe burns are at increased risk for local and systemic
      infections. The incidence of fungal infections has increased in recent years, and
      these infections represent a major issue in burn intensive care units. Herein, we
      report three cases of fungal infection due to Candida species occurring in
      patients undergoing supportive therapy and antibiotic treatment during their
      hospitalization. Two of these patients were infected with Candida parapsilosis,
      and one was infected with Candida albicans. The risk factors for these patients'
      Candida infections were multiple and prolonged courses of antimicrobial
      treatment, steroid treatment, tracheal intubation and smoke inhalation.
      Susceptibility testing of nine antifungal compounds was performed, and the
      minimum inhibitory concentration (MIC) values of all isolated strains were lower
      than the breakpoint MIC value for resistance of the relevant drug. All three
      patients were cured by treatment with antifungal agents. Candida infection may
      occur 1 - 3 weeks after thermal injury, and the prompt recognition and treatment
      of such infections with antifungal therapies may result in decreased morbidity
      and mortality associated with these infections in burn patients.

PMID- 22882952
TI  - Breakthrough trichosporonosis in patients receiving echinocandins: case report
      and literature review.
AB  - Trichosporon species now ranks as the second most common cause of disseminated
      yeast infections with a high mortality rate. Breakthrough trichosporonosis in
      patients receiving echinocandins therapy is being recognized recently. We present
      a case of breakthrough trichosporonosis with acute viral myocarditis while
      receiving caspofungin therapy. Trichosporon infection should be considered in
      patients, who have risk factors for invasive fungal infection and develop
      unexplained clinical manifestations of infection despite treatment with
      echinocandins.

PMID- 22882953
TI  - Hepatitis B virus reactivation in a chronic myeloid leukemia patient treated with
      imatinib mesylate.
AB  - Imatinib mesylate is a molecular targeted agent for treating chronic myeloid
      leukemia (CML) and gastrointestinal stromal tumor. Although imatinib mesylate is
      not regarded as an immunosuppressive agent, few studies have also shown that it
      may impair immune response. In this report, we present a case of transient
      hepatitis B virus (HBV) reactivation during imatinib mesylate treatment for CML.

PMID- 22882954
TI  - Massive hemoptysis and hemothorax: a rare but fatal complication of intralobar
      sequestration.
AB  - Intralobar sequestration (ILS) is an uncommon abnormality that accounts for 75%
      of all pulmonary sequestrations. Over the years there have been several reports
      of various presenting signs of which hemoptysis was commonly described, however,
      massive hemoptysis and hemothorax is extremely rare in literature. We present a
      case of a 45-year-old man who died of fatal complication from an ILS. This case
      report shows an uncommon presentation of ILS with massive hemoptysis and
      hemothorax resulting in a dramatic course of disease and a fatal outcome, and for
      this reason in the absence of trauma or other causes for massive hemoptysis,
      hemothorax, or lung hematoma, this possibility should be kept in mind so as to
      avoid misdiagnosis, and resection of the sequestered tissue should be considered
      in all patients.

PMID- 22882955
TI  - Prevalence and molecular identification of Borrelia spirochetes in Ixodes
      granulatus ticks collected from Rattus losea on Kinmen Island of Taiwan.
AB  - BACKGROUND: Ixodes granulatus is widely distributed in various countries of
      Southeast Asia and Taiwan. Although this tick species is presumed to be the
      vector for the enzoonotic transmission of Borrelia spirochetes in the Taiwan
      area, the prevalence of infection and genetic diversity of Borrelia spirochetes
      harbored by this tick species need to be further determined. METHODS: DNA
      extraction was performed from individual tick specimens collected from Rattus
      losea on Kinmen Island of Taiwan. Borrelia infection in I. granulatus ticks was
      detected by performing a specific PCR assay based on the 5S-23S intergenic spacer
      amplicon gene of B. burgdorferi sensu lato. The genetic identities of detected
      spirochetes were identified by gene sequencing and phylogenetic analysis.
      RESULTS: Borrelia infection was detected in nymph, male, and female stages of
      Ixodes granulatus ticks with an infection rate of 42.9%, 36%, and 52.7%,
      respectively. Genospecies identification reveals that B. valaisiana is the main
      genotype (70.7%) as compared to the genotype of B. burgdorferi sensu stricto
      (15.4%). Phylogenetic analysis revealed that these detected spirochetes were
      genetically affiliated to the genospecies B. valaisiana and B. burgdorferi sensu
      stricto, with a high sequence homology within the genospecies of B. valaisiana
      (95.8 to 100%) and B. burgdorferi sensu stricto (97.2 to 100%), respectively.
      CONCLUSIONS: This study highlights the significance of high prevalence and
      genetic diversity of Borrelia spirochetes in I. granulatus ticks collected from
      Rattus losea on Kinmen Island of Taiwan. Intraspecific analysis also revealed
      that B. valaisiana species detected in Kinmen Island can be easily distinguished
      from the European group of B. valaisiana and other genospecies of Borrelia
      spirochetes. This may imply an enzoonotic cycle between I. granulatus ticks and
      rodent hosts that maintains Borrelia spirochetes in Kinmen Island as well as
      Southeast Asia.

PMID- 22882956
TI  - Impact of UV/H2O2 advanced oxidation treatment on molecular weight distribution
      of NOM and biostability of water.
AB  - The presence of natural organic matter (NOM) poses several challenges to the
      commercial practice of UV/H(2)O(2) process for micropollutant removal. During the
      commercial application of UV/H(2)O(2) advanced oxidation treatment, NOM is broken
      down into smaller species potentially affecting biostability by increasing
      Assimilable Organic Carbon (AOC) and Biodegradable Organic Carbon (BDOC) of
      water. This work investigated the potential impact of UV/H(2)O(2) treatment on
      the molecular weight distribution of NOM and biostability of different water
      sources. A recently developed flow cytometric method for enumeration of bacteria
      was utilized to assess biological stability of the treated water at various
      stages through measurement of AOC. BDOC was also assessed for comparison and to
      better study the biostability of water. Both AOC and BDOC increased by about 3-4
      times over the course of treatment, indicating the reduction of biological
      stability. Initial TOC and the source of NOM were found to be influencing the
      biostability profile of the treated water. Using high performance size exclusion
      chromatography, a wide range of organic molecule weights were found responsible
      for AOC increase; however, low molecular weight organics seemed to contribute
      more. Positive and meaningful correlations were observed between BDOC and AOC of
      different waters that underwent different treatments.

PMID- 22882957
TI  - Morphological and physicochemical characteristics of iron corrosion scales formed
      under different water source histories in a drinking water distribution system.
AB  - The corrosion scales on iron pipes could have great impact on the water quality
      in drinking water distribution systems (DWDS). Unstable and less protective
      corrosion scale is one of the main factors causing "discolored water" issues when
      quality of water entering into distribution system changed significantly. The
      morphological and physicochemical characteristics of corrosion scales formed
      under different source water histories in duration of about two decades were
      systematically investigated in this work. Thick corrosion scales or densely
      distributed corrosion tubercles were mostly found in pipes transporting surface
      water, but thin corrosion scales and hollow tubercles were mostly discovered in
      pipes transporting groundwater. Magnetite and goethite were main constituents of
      iron corrosion products, but the mass ratio of magnetite/goethite (M/G) was
      significantly different depending on the corrosion scale structure and water
      source conditions. Thick corrosion scales and hard shell of tubercles had much
      higher M/G ratio (>1.0), while the thin corrosion scales had no magnetite
      detected or with much lower M/G ratio. The M/G ratio could be used to identify
      the characteristics and evaluate the performances of corrosion scales formed
      under different water conditions. Compared with the pipes transporting ground
      water, the pipes transporting surface water were more seriously corroded and
      could be in a relatively more active corrosion status all the time, which was
      implicated by relatively higher siderite, green rust and total iron contents in
      their corrosion scales. Higher content of unstable ferric components such as
      gamma-FeOOH, beta-FeOOH and amorphous iron oxide existed in corrosion scales of
      pipes receiving groundwater which was less corroded. Corrosion scales on
      groundwater pipes with low magnetite content had higher surface area and thus
      possibly higher sorption capacity. The primary trace inorganic elements in
      corrosion products were Br and heavy metals. Corrosion products obtained from
      pipes transporting groundwater had higher levels of Br, Ti, Ba, Cu, Sr, V, Cr,
      La, Pb and As.

PMID- 22882958
TI  - Myocardial and circulating levels of microRNA-21 reflect left ventricular
      fibrosis in aortic stenosis patients.
AB  - BACKGROUND: Various human cardiovascular pathophysiological conditions associate
      aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as
      promising biomarkers. In mice, myocardial miR-21 overexpression is related to
      cardiac fibrosis elicited by pressure overload. This study was designed to
      determine the role of myocardial and plasmatic miR-21 in the maladaptive
      remodeling of the extracellular matrix induced by pressure overload in aortic
      stenosis (AS) patients and the clinical value of miR-21 as a biomarker for
      pathological myocardial fibrosis. METHODS: In left ventricular biopsies from 75
      AS patients and 32 surgical controls, we quantified the myocardial transcript
      levels of miR-21, miR-21-targets and ECM- and TGF-beta-signaling-related
      elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS
      patients. In situ hybridization of miR-21 was performed in myocardial sections.
      RESULTS: The myocardial and plasma levels of miR-21 were significantly higher in
      the AS patients compared with the controls and correlated directly with the
      echocardiographic mean transvalvular gradients. miR-21 overexpression was
      confined to interstitial cells and absent in cardiomyocytes. Using bootstrap
      validated multiple linear regression, the variance in myocardial collagen
      expression was predicted by myocardial miR-21 (70% of collagen variance) or
      plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK
      and PDCD4, and effectors of TGF-beta signaling. CONCLUSIONS: Our results support
      the role of miR-21 as a regulator of the fibrotic process that occurs in response
      to pressure overload in AS patients and underscore the value of circulating miR
      21 as a biomarker for myocardial fibrosis.

PMID- 22882959
TI  - Impact of epicardial fat volume on coronary artery disease in symptomatic
      patients with a zero calcium score.
AB  - BACKGROUND: This study sought to evaluate the prevalence of coronary artery
      disease (CAD) and the impact of epicardial fat volume (EFV) on CAD in symptomatic
      patients with a zero calcium score (CS) using multislice computed tomography
      (MSCT). METHODS: In this study, 1308 consecutive symptomatic patients who
      underwent 64-slice MSCT with a zero CS were evaluated. EFV was quantified with CS
      data sets. Presence of an obstructive plaque (diameter stenosis >50%) and a CT
      derived vulnerable plaque, which was defined as a plaque with remodeling index
      >1.10 and mean CT density value <3 0HU, was assessed with a CT coronary
      angiography. RESULTS: Obstructive plaques were detected in 86 patients (7%) and
      CT-derived vulnerable plaques in 63 (5%). EFV was larger in patients with
      obstructive plaques than no plaque (124.3 +/- 43.2 cm(3) vs. 95.1 +/- 40.3 cm(3);
      p<0.01). Patients with CT-derived vulnerable plaques had a greater amount of EFV
      than no plaque (133.0 +/- 40.2 cm(3) vs. 95.1 +/- 40.3 cm(3); p<0.01).
      Multivariate analysis revealed EFV as a predictor of the presence of an
      obstructive and a CT-derived vulnerable plaque (per 10 cm(3); Odds ratio (OR)
      1.10; 95% confidence interval (CI), 1.04-1.16; p<0.01 and OR 1.19; 95% CI, 1.12
      1.27; p<0.01). The combination of EFV and Framingham risk score (FRS) resulted in
      an area under the receiver-operating characteristic curve for prediction of
      obstructive and CT-derived vulnerable plaque of 0.75 and 0.75, which was
      significantly higher than 0.68 and 0.64 for FRS alone (p=0.02 and p<0.01).
      CONCLUSIONS: A zero CS doesn't exclude CAD and EFV can be a useful marker of CAD
      in symptomatic zero CS patients.

PMID- 22882960
TI  - Rates and determinants of progressive aortic valve dysfunction in aortic
      coarctation.
AB  - PURPOSE: Aortic valve dysfunction is common in coarctation patients(CoA).
      Bicuspid aortic valve (BAV) in CoA is associated with aortic valve stenosis (AS),
      aortic valve regurgitation (AR), and ascending aortic dilatation. The aim of this
      study was to evaluate the progression of and predictors for aortic valve
      dysfunction in CoA. METHODS: 96 CoA patients prospectively underwent
      echocardiography twice between 2001 and 2010. AS was defined as an aortic valve
      gradient >= 20 mmHg, AR as none/minor, or moderate/severe. Aortic dilatation as
      an ascending aortic diameter >= 37 mm. RESULTS: All patients (median age 28.0
      years, range 17-61 years; male 57%) were followed with a median follow-up of 7.0
      years. Sixty patients (63%) had BAV. At baseline 10 patients had AS (10%, 9 BAV),
      6 patients AR (6%, 3 BAV) and 11 patients aortic dilatation (11%, 11 BAV). At
      follow-up 15 patients had AS (15%, 13 BAV) and 12 patients AR. (13%, 8 BAV).
      Median AS progression was 1.1 mmHg/5 years (range - 13-28). Determinants for AS
      at follow-up were age (beta=0.20, P=0.01), aortic dilatation (beta=4.6, P=0.03),
      and baseline aortic valve gradient (beta=0.93, P<0.001). BAV was predictive for
      AR. (beta=0.91, P=0.049). CONCLUSION: Progression of AS in adult CoA patients is
      mild in this young population. Older age, aortic dilatation and the baseline
      aortic valve gradient are determinants for AS at follow-up. BAV is predictive for
      AR. These findings point towards a common embryological pathway of both valvular
      and aortic disease in CoA.

PMID- 22882961
TI  - Who is at low risk for cardiovascular disease? An assessment of different
      definitions.
AB  - BACKGROUND: There is little information regarding the determinants and trends of
      the prevalence of low cardiovascular risk factor (RF) profile in the general
      population. The aim of this study was to assess the prevalence and trends of low
      RF profile in the Swiss population according to different definitions. METHODS:
      Population-based cross-sectional studies conducted in 1984-1986 (N=3300), 1988
      1989 (N=3331), 1992-1993 (N=3133) and 2003-2006 (N=6170) and restricted to age
      group 35-75 years. Seven different definitions of low RF profile were used to
      assess determinants, while two definitions were used to assess trends. RESULTS:
      Prevalence of low RF profile varied between 6.5% (95% confidence interval: 5.9
      7.1) and 9.7% (9.0-10.5) depending on the definition used. This prevalence was
      higher than in other countries. Irrespective of the definition used, the
      prevalence of low RF profile was higher in women and in physically active
      participants, and decreased with increasing age or in the presence of a family
      history of cardiovascular disease. Using one definition, the prevalence of low RF
      profile increased from 3.8% (3.1-4.5) in 1984-1986 to 6.7% (6.1-7.3) in 2003
      2006; using another definition, the results were 5.9% (5.1-6.8) and 9.7% (9.0
      10.5), respectively. CONCLUSION: Switzerland is characterized by a high and
      increasing prevalence of low RF profile within the age group 35 to 75,
      irrespective of the criteria used. This high prevalence might partly explain the
      low and decreasing trend in cardiovascular mortality rates.

PMID- 22882962
TI  - Takotsubo cardiomyopathy, mental stress and the Kounis syndrome.

PMID- 22882963
TI  - Acute aortic dissection: epidemiology and outcomes.
AB  - BACKGROUND: Little epidemiological information on acute aortic dissection (AAD)
      is available in the literature. The objective of the present study was to
      determine the incidence and mortality rates of AAD in the general population and
      to analyze its clinical features. METHODS: Data from the Emilia-Romagna regional
      database of hospital admissions was analyzed. Urgent admissions with the
      diagnosis of dissection of the aorta, dissection of the thoracic aorta and
      dissection of the thoracoabdominal aorta were selected. RESULTS: Between January
      2000 and December 2008, 1499 Emilia-Romagna residents were hospitalized with a
      diagnosis of AAD. The patients were divided into three groups: Group A, 617
      patients (41.2%) surgically treated for type A AAD; Group B, 93 complicated
      patients (6.2%) with type B AAD treated by endovascular stent-grafting and Group
      C, 789 patients (52.6%) suffering from any type of AAD medically treated. The
      overall annual incidence rate was 4.7%/100,000 people and was higher for men than
      for women (6.7% vs 2.9%).Two hundred ninety-six patients (19.8%) were 80 years of
      age or older.The overall in-hospital mortality rate was 27.7%, with mortality
      rates of 21.1%, 26.9% and 33% in Groups A, B and C, respectively. CONCLUSION: The
      incidence of AAD is not negligible and a notable rate of patients is ultra
      octogenarian. A large number of patients with AAD had no surgery or
      interventional treatment. The results of surgical treatment for patients with
      type A dissection are acceptable but the results obtained in patients with
      complicated type B dissection who were treated with an endoprosthesis are dismal.

PMID- 22882964
TI  - Severity of left ventricular dysfunction in heart failure patients affects the
      degree of serum-induced cardiomyocyte apoptosis. Importance of inflammatory
      response and metabolism.
AB  - BACKGROUND/OBJECTIVES: In heart failure pro-inflammatory cytokines contribute to
      cardiomyocytes loss by apoptosis and play a role in the remodelling of the
      extracellular matrix (ECM). Myocardial injury recruits endothelial progenitor
      cells (EPCs) to the site of damage and stimulates their differentiation,
      contributing to myocardial tissue repair. We investigated if the severity of left
      ventricular dysfunction in heart failure patients (HF) may influence the ability
      of serum to induce cardiomyocytes death and whether this effect is affected by
      inflammation and intracellular oxidative stress pathways. METHODS: Adult murine
      cardiomyocytes HL-5 were incubated with 2% human serum from patients with heart
      failure (NYHA classes I to IV). Apoptosis was analysed by two different methods.
      TNF-alpha, IL-1beta, IL-6, matrix metalloproteinase 1 (MMP-1) and tissue
      inhibitor of metalloproteinases 1 (TIMP-1) were measured in sera from patients.
      RESULTS: Cytokine levels were higher in sera from moderate-severe CHF compared to
      that of patients with mild CHF. Levels of CD117(+) (c-Kit(+)) cells and EPCs were
      significantly lower in blood from moderate-severe HF patients. Serum from HF
      patients induced a significantly higher ROS production involving p38 MAPK
      signalling and apoptosis in cardiomyocytes. NAC treatment prevented serum-induced
      oxidative effects. The increase of AMPK phosphorylation showed an involvement of
      FFA beta-oxidation during apoptotic stress. CONCLUSIONS: All these alterations
      could be used as predictive factors of worsening in heart failure and culture of
      cardiomyocytes could be employed to test pharmacological effects.

PMID- 22882965
TI  - Right to left shunting through communications between the left superior
      intercostal vein tributaries and the left atrium: a potential cause of
      paradoxical embolism.
AB  - OBJECTIVES: To investigate the role of collateral venous pathways between the
      left brachiocephalic vein (LBV) and the left atrium through an arcade comprising
      the left superior intercostal vein (LSICV), left vertical vein (LVV), and
      pulmonary veins as a potential cause of paradoxical embolism. METHODS: A
      retrospective search was performed to find symptomatic patients with negative
      work up for paradoxical emboli whose chest CT or MR angiography by left arm
      contrast injection showed a visible right to left shunt through the LSICV/LVV
      collateral pathway (symptomatic group). We also evaluated the characteristics of
      this collateral pathway in 150 chest CT angiographies from general referrals
      (comparison group). RESULTS: We found 7 symptomatic patients. Initial
      presentations included neurological symptoms in all patients and episodes of
      hypoxemia in three patients. Communications between the LBV and left atrium
      through the LSICV/LVV pathway was seen is all 7 cases and confirmed by
      transesophageal echocardiography in two. An abnormal LBV was seen in 6 cases
      (absence in one, stenosis in 5). Moderate superior vena cava stenosis was seen in
      one and acute right subclavian vein thrombosis in one. Six patients had past
      history of an upper extremity central line placement. In the comparison group,
      LSICV was seen in 73 (48%), connecting to the hemiazygos vein in 41, to a LVV in
      19 and to the left atrium in 7. CONCLUSION: LSICV/LVV collaterals are common and
      can be a potential route for paradoxical emboli especially when stenosis of a
      draining vein such as LBV exists.

PMID- 22882967
TI  - A systematic review of systematic reviews of interventions to improve maternal
      mental health and well-being.
AB  - OBJECTIVE: to identify non-invasive interventions in the perinatal period that
      could enable midwives to offer effective support to women within the area of
      maternal mental health and well-being. METHODS: a total of 9 databases were
      searched: MEDLINE, PubMed, EBSCO (CINAHL/British Nursing Index), MIDIRS Online
      Database, Web of Science, The Cochrane library, CRD (NHS EED/DARE/HTA), Joanne
      Briggs Institute and EconLit. A systematic search strategy was formulated using
      key MeSH terms and related text words for midwifery, study aim, study design and
      mental health. Inclusion criteria were articles published from 1999 onwards,
      English language publications and articles originating from economically
      developed countries, indicated by membership of the Organisation for Economic Co
      operation and Development (OECD). Data were independently extracted using a data
      collection form, which recorded data on the number of papers reviewed, time frame
      of the review, objectives, key findings and recommendations. Summary data tables
      were set up outlining key data for each study and findings were organised into
      related groups. The methodological quality of the reviews was assessed based on
      predefined quality assessment criteria for reviews. FINDINGS: 32 reviews were
      identified as examining interventions that could be used or co-ordinated by
      midwives in relation to some aspect of maternal mental health and well-being from
      the antenatal to the postnatal period and met the inclusion criteria. The review
      highlighted that based on current systematic review evidence it would be
      premature to consider introducing any of the identified interventions into
      midwifery training or practice. However there were a number of examples of
      possible interventions worthy of further research including midwifery led models
      of care in the prevention of postpartum depression, psychological and
      psychosocial interventions for treating postpartum depression and facilitation/co
      ordination of parent-training programmes. No reviews were identified that
      supported a specific midwifery role in maternal mental health and well-being in
      pregnancy, and yet, this is the point of most intensive contact. KEY CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: This systematic review of systematic reviews
      provides a valuable overview of the current strengths and gaps in relation to
      maternal mental health interventions in the perinatal period. While there was
      little evidence identified to inform the current role of midwives in maternal
      mental health, the review provides the opportunity to reflect on what is
      achievable by midwives now and in the future and the need for high quality
      randomised controlled trials to inform a strategic approach to promoting maternal
      mental health in midwifery.

PMID- 22882966
TI  - Choice between prostatectomy and radiotherapy when men are eligible for both: a
      randomized controlled trial of usual care vs decision aid.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Many patients are
      eligible for more than one treatment option for prostate cancer. In usual care,
      urologists have a large influence on the treatment choice. Decision aids,
      providing balanced information on the pros and cons of different treatment
      options, improve the match between patient preferences and treatment received. In
      men eligible for both surgery and external beam radiotherapy, treatment choice
      differed by hospital. Across the participating hospitals, the decision aid
      consistently led to fewer patients remaining undecided on their treatment
      preference and more patients choosing brachytherapy. OBJECTIVES: To examine the
      treatment choice for localized prostate cancer in selected men who were eligible
      for both prostatectomy and radiotherapy. To examine whether increased patient
      participation, using a decision aid, affected the treatment choice. PATIENTS AND
      METHODS: From 2008 to 2011, 240 patients with localized prostate cancer were
      enrolled from three separate hospitals. They were selected to be eligible for
      both prostatectomy and external beam radiotherapy. Brachytherapy was a third
      option for about half of the patients. In this randomized controlled trial,
      patients were randomized to a group which only discussed their treatment with
      their specialist (usual care group) and a group which received additional
      information from a decision aid presented by a researcher (decision aid group).
      The decision aid was based on a literature review. Predictors of treatment choice
      were examined. RESULTS: Treatment choice was affected by the decision aid (P =
      0.03) and by the hospital of intake (P < 0.001). The decision aid led to more
      patients choosing brachytherapy (P = 0.02) and fewer patients remaining undecided
      (P < 0.05). Prostatectomy remained the most frequently preferred treatment. Age,
      tumour characteristics or pretreatment urinary, bowel or erectile functioning did
      not affect the choice in this selected group. Patients choosing brachytherapy
      assigned more weight to convenience of the procedure and to maintaining erectile
      function. CONCLUSIONS: Traditionally, patient characteristics differ between
      surgery and radiotherapy groups, but not in this selected group of patients. Men
      eligible for both prostatectomy and radiotherapy mostly preferred prostatectomy,
      and the treatment choice was influenced by the hospital they visited. Giving
      patients evidence-based information, by means of a decision aid, led to an
      increase in brachytherapy.

PMID- 22882969
TI  - Assessing psychological health in midwifery practice: a validation study of the
      Four-Dimensional Symptom Questionnaire (4DSQ), a Dutch primary care instrument.
AB  - OBJECTIVE: the Four-Dimensional Symptom Questionnaire (4DSQ) is a validated self
      report questionnaire, developed for general practice to assess the level of
      distress, somatization, depression and anxiety among patients. This study
      evaluated the validity of this instrument for midwifery practice by differential
      item functioning analysis. DESIGN: cross-sectional. SETTING AND PARTICIPANTS: the
      focal group consisted of clients of 15 primary care midwifery practices in The
      Netherlands (n=478). The reference group consisted of Dutch female primary care
      patients, matched for age (n=478). MEASUREMENTS AND FINDINGS: Differential item
      functioning (DIF) was assessed by ordinal regression and the Mantel Haenszel
      method. The impact of DIF was measured by linear regression. The depression scale
      was free of DIF. The somatization, distress and anxiety scale contained items
      with DIF. Because of DIF, pregnant and postpartum women had on average 1-2 points
      lower predicted scores on the somatization scale and 1 point lower scores on the
      anxiety scale. On the distress scale the midwifery group had 1-2 higher predicted
      scores. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the 4DSQ is a valid
      instrument for casefinding of psychological disease in midwifery practice,
      provided cut-off scores of the distress, anxiety and somatization scale be
      adapted.

PMID- 22882968
TI  - An exploration of illness beliefs in mothers with postnatal depression.
AB  - OBJECTIVE: to explore illness beliefs in women with postnatal depression and
      suggest an appropriate health belief model. About 10% of recently delivered
      mothers suffer from depression. Postnatal depression may differ from depression
      occurring at other times in an individual's life not only symptomatically but
      also experiences, perceptions and beliefs about the illness differ because of the
      individual's specific role as a carer for a newborn baby. Whilst illness beliefs
      have been extensively examined using models from physical health, recent studies
      have pointed out that physical health models may not provide an appropriate
      framework to explore mental health difficulties and require adapting. DESIGN:
      qualitative study using face-to-face interviews for data collection. SETTING:
      Greater Manchester, England. METHODS: as illness beliefs have not yet been
      formally assessed using established questionnaires, the present study employed
      qualitative methodology to explore illness beliefs in mothers with postnatal
      depression (PND). Semi-structured interviews were conducted with 11 participants
      who were depressed following the birth of their child. Interview transcripts were
      analysed using grounded theory methodology. The point of theoretical sufficiency
      was reached with this sample size. FINDINGS: the rich data allowed for a theory
      of illness beliefs in PND to be developed encompassing six core categories:
      'unmet expectations', 'identifying stressors in their life context', 'conflict
      over label', 'antidepressants: the lesser of two evils', 'loss of time' and
      'uncertain futures.' KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: participants
      made multiple appraisals of their PND in light of their initial difficulties,
      their improvements and consequences, the future and subsequent service
      involvement. Participants' narratives were conflicting and uncertain with
      internal struggles evident as mothers were torn between their desire to be good
      mothers and their perceptions that PND meant that they were not good enough
      mothers. Thus, the themes identified in this study did not match onto the key
      dimensions postulated by Leventhal's self-regulation model of illness beliefs.

PMID- 22882970
TI  - Cambodian migrant women's postpartum experiences in Victoria, Australia.
AB  - OBJECTIVE: to explore the postpartum experiences of Cambodian born migrant women
      who gave birth for the first time in Victoria, Australia between 2000 and 2010.
      DESIGN: an ethnographic study with 35 women using semi-structured and
      unstructured interviews and participant observation; this paper draws on
      interviews with 20 women who fit the criteria of first time mothers who gave
      birth in an Australian public hospital. SETTING: the City of Greater Dandenong,
      Victoria Australia. PARTICIPANTS: twenty Cambodian born migrant women aged 23-30
      years who gave birth for the first time in a public hospital in Victoria,
      Australia. FINDINGS: after one or two home visits by midwives in the first 10 day
      postpartum women did not see a health professional until 4-6 weeks postpartum
      when they presented to the MCH centre. Women were home alone, experienced
      loneliness and anxiety and struggled with breast feeding and infant care while
      they attempted to follow traditional Khmer postpartum practices. IMPLICATIONS FOR
      PRACTICE: results of this study indicate that Cambodian migrant women who are
      first time mothers in a new country with no female kin support in the postpartum
      period experience significant emotional stress, loneliness and social isolation
      and are at risk of developing postnatal depression. These women would benefit
      from the introduction of a midwife-led model of care, from antenatal through to
      postpartum, where midwives provide high-intensity home visits, supported by
      interpreters, and when required refer women to professionals and community
      services such as Healthy Mothers Healthy Babies (Victoria Department of Health,
      2011) for up to 6 weeks postpartum.

PMID- 22882971
TI  - Comparison of non-crystalline silica nanoparticles in IL-1beta release from
      macrophages.
AB  - BACKGROUND: Respirable crystalline silica (silicon dioxide; SiO2, quartz)
      particles are known to induce chronic inflammation and lung disease upon long
      term inhalation, whereas non-crystalline (amorphous) SiO2 particles in the
      submicrometre range are regarded as less harmful. Several reports have
      demonstrated that crystalline, but also non-crystalline silica particles induce
      IL-1beta release from macrophages via the NALP3-inflammasome complex (caspase-1,
      ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim
      was to study the potential of different non-crystalline SiO2 particles from the
      nano- to submicro-sized range to activate IL-1beta responses in LPS-primed
      RAW264.7 macrophages and primary rat lung macrophages. The role of the NALP3
      inflammasome and up-stream mechanisms was further explored in RAW264.7 cells.
      RESULTS: In the present study, we have shown that 6 h exposure to non-crystalline
      SiO2 particles in nano- (SiNPs, 5-20 nm, 50 nm) and submicro-sizes induced strong
      IL-1beta responses in LPS-primed mouse macrophages (RAW264.7) and primary rat
      lung macrophages. The primary lung macrophages were more sensitive to Si-exposure
      than the RAW-macrophages, and responded more strongly. In the lung macrophages,
      crystalline silica (MinUsil 5) induced IL-1beta release more potently than the
      non-crystalline Si50 and Si500, when adjusted to surface area. This difference
      was much less pronounced versus fumed SiNPs. The caspase-1 inhibitor zYVAD and
      RNA silencing of the NALP3 receptor reduced the particle-induced IL-1beta release
      in the RAW264.7 macrophages. Furthermore, inhibitors of phagocytosis, endosomal
      acidification, and cathepsin B activity reduced the IL-1beta responses to the
      different particles to a similar extent. CONCLUSIONS: In conclusion, non
      crystalline silica particles in the nano- and submicro-size ranges seemed to
      induce IL-1beta release from LPS-primed RAW264.7 macrophages via similar
      mechanisms as crystalline silica, involving particle uptake, phagosomal leakage
      and activation of the NALP3 inflammasome. Notably, rat primary lung macrophages
      were more sensitive with respect to silica-induced IL-1beta release. The
      differential response patterns obtained suggest that silica-induced IL-1beta
      responses not only depend on the particle surface area, but on factors and/or
      mechanisms such as particle reactivity or particle uptake. These findings may
      suggest that bacterial infection via LPS may augment acute inflammatory effects
      of non-crystalline as well as crystalline silica particles.

PMID- 22882972
TI  - Is waist circumference a better predictor of blood pressure, insulin resistance
      and blood lipids than body mass index in young Chilean adults?
AB  - BACKGROUND: It has been reported that waist circumference (WC) is a better
      predictor of cardiovascular risk factors than body mass index (BMI), although the
      findings have not been consistent. The aim of this study was to assess which
      measurement, BMI or WC, is more strongly associated with blood pressure,
      homeostatic model assessment (HOMA) and blood lipids in young Chilean adults.
      METHODS: 999 subjects aged 22 to 28 years were randomly selected from a registry
      of individuals born between 1974 and 1978 at the Hospital of Limache, Chile.
      Weight, height, WC, blood pressure, HOMA and lipoproteins were assessed in a
      cross-sectional study. RESULTS: In multivariable regressions BMI and WC were
      associated with blood pressure, HOMA and lipoproteins at similar level of
      explained variation (R2 between 1.6 % for Low Density Lipoproteins (LDL) and 15.6
      %, the highest for HOMA and triglycerides) and similarly OR in standardised
      logistic regressions between 1.1 (95 % CI: 0.9 and 1.4) for LDL and 2.9 (95 % CI:
      2.4 and 3.4) for elevated HOMA. When both WC and BMI were included in the model
      collinearity was high and only for HOMA was there a small independent
      contribution of each index (R2 = 1 %); for other outcomes the pattern was
      inconsistent. CONCLUSION: The strength of the associations of WC and BMI for any
      cardiovascular risk factors was similar, but highest for HOMA and triglycerides.
      WC and BMI are equally useful for monitoring the consequences of obesity in young
      adults.

PMID- 22882973
TI  - Identifying a role of the actin capping protein CapZ in beta-adrenergic receptor
      signalling.
AB  - AIM: beta-Adrenergic receptor activation increases myocardial contractility, in
      part through protein kinase A (PKA)-dependent modification of cardiac
      myofilaments. PKA regulation of cardiac myofilaments is contingent influenced by
      protein kinase C (PKC) phosphorylation of troponin I (TnI). Reductions in the
      cardiac Z-disc protein CapZ attenuate PKC regulation of myofilament activation.
      We hypothesized that CapZ-deficient transgenic mouse hearts respond poorly to
      beta-adrenergic receptor activation, as a result of impaired PKC activation.
      METHODS: Wild-type and CapZ-deficient transgenic mice were treated with the beta
      adrenergic receptor agonist isoproterenol (ISO) and whole heart function assessed
      by echocardiography. Cardiac myofilaments were isolated post-ISO treatment and
      subjected to an actomyosin MgATPase assay and protein phosphorylation gels.
      RESULTS: CapZ-deficient transgenic mouse hearts exhibited increased contractility
      and myofilament calcium sensitivity at baseline, as compared to wild-type mice.
      In wild-type mice, ISO increased myocardial contractility and decreased
      myofilament calcium sensitivity, along with an increase in TnI phosphorylation.
      CapZ-deficient transgenic mice responded to ISO treatment, and myocardial
      functional differences between transgenic and wild-type mice were abolished. ISO
      dependent changes in myofilament activation in transgenic mice were similar to
      those observed in wild-type. TnI phosphorylation was similarly increased in wild
      type and transgenic mice following ISO treatment, while CapZ-deficient transgenic
      mouse myofilaments also exhibited increased myosin-binding protein C
      phosphorylation. Differences in myofilament protein phosphorylation patterns
      suggest the intracellular mechanisms utilized by beta-adrenergic receptor
      activation are different than that seen in wild-type hearts. CONCLUSIONS: These
      data further support the concept that the cardiac Z-disc protein is a regulator
      of myofilament function and intracellular signalling transduction.

PMID- 22882974
TI  - Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2
      dependent mechanism.
AB  - ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of
      transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and
      signaling, with important implications in cancer. Therefore, mechanisms that
      regulate the levels and activity of ADAM12 at the cell-surface are possibly
      crucial in these contexts. We here investigated internalization and subsequent
      recycling or degradation of ADAM12 as a potentially important regulatory
      mechanism. Our results show that ADAM12 is constitutively internalized primarily
      via the clathrin-dependent pathway and is subsequently detected in both early and
      recycling endosomes. The protease activity of ADAM12 does not influence this
      internalization mechanism. Analysis of essential elements for internalization
      established that proline-rich regions in the cytoplasmic domain of ADAM12,
      previously shown to interact with Src-homology 3 domains, were necessary for
      proper internalization. These sites in the ADAM12 cytoplasmic domain interacted
      with the adaptor protein growth factor receptor-bound protein 2 (Grb2) and
      knockdown of Grb2 markedly reduced ADAM12 internalization. These studies
      establish that internalization is indeed a mechanism that regulates ADAM cell
      surface levels and show that ADAM12 internalization involves the clathrin
      dependent pathway and Grb2.

PMID- 22882976
TI  - [The clinical practice guideline for the diagnosis and treatment of atrial
      fibrillation. Medical reflections from the daily practice].
AB  - Atrial fibrillation (AF) represents a global public health problem. The
      implementation of a clinical practice guideline is essential to standardize the
      diagnosis, treatment and prognosis of this rhythm disturbance. However, due to
      the wide clinical spectrum which is associated with AF, it makes difficult to
      standardize the recommendations and cause that are not always appropriate
      interpretations of the same setting, so there will be some clinical reflections
      of the recommendations in the clinical practice guidelines published in this
      journal, to assist the medical not specialist to put them in everyday clinical
      setting.

PMID- 22882977
TI  - [Ralph M. Steinman, 2011 Nobel for his contributions on immunity].
AB  - Ralph M. Steinman was the recipient of the 2011 Nobel Prize of Physiology and
      Medicine due to the discovery of dendritic cells, which have a crucial role on
      the onset of acquired immunity, a fundamental event in the organism's defense.
      Today, dendritic cells are used in the development of vaccines and in cancer
      therapy. Steinman's contributions have been fundamental in the understanding of
      immunity.

PMID- 22882975
TI  - Non-canonical peroxisome targeting signals: identification of novel PTS1
      tripeptides and characterization of enhancer elements by computational
      permutation analysis.
AB  - BACKGROUND: High-accuracy prediction tools are essential in the post-genomic era
      to define organellar proteomes in their full complexity. We recently applied a
      discriminative machine learning approach to predict plant proteins carrying
      peroxisome targeting signals (PTS) type 1 from genome sequences. For Arabidopsis
      thaliana 392 gene models were predicted to be peroxisome-targeted. The
      predictions were extensively tested in vivo, resulting in a high experimental
      verification rate of Arabidopsis proteins previously not known to be peroxisomal.
      RESULTS: In this study, we experimentally validated the predictions in greater
      depth by focusing on the most challenging Arabidopsis proteins with unknown non
      canonical PTS1 tripeptides and prediction scores close to the threshold. By in
      vivo subcellular targeting analysis, three novel PTS1 tripeptides (QRL>, SQM>,
      and SDL>) and two novel tripeptide residues (Q at position -3 and D at pos. -2)
      were identified. To understand why, among many Arabidopsis proteins carrying the
      same C-terminal tripeptides, these proteins were specifically predicted as
      peroxisomal, the residues upstream of the PTS1 tripeptide were computationally
      permuted and the changes in prediction scores were analyzed. The newly identified
      Arabidopsis proteins were found to contain four to five amino acid residues of
      high predicted targeting enhancing properties at position -4 to -12 in front of
      the non-canonical PTS1 tripeptide. The identity of the predicted targeting
      enhancing residues was unexpectedly diverse, comprising besides basic residues
      also proline, hydroxylated (Ser, Thr), hydrophobic (Ala, Val), and even acidic
      residues. CONCLUSIONS: Our computational and experimental analyses demonstrate
      that the plant PTS1 tripeptide motif is more diverse than previously thought,
      including an increasing number of non-canonical sequences and allowed residues.
      Specific targeting enhancing elements can be predicted for particular sequences
      of interest and are far more diverse in amino acid composition and positioning
      than previously assumed. Machine learning methods become indispensable to predict
      which specific proteins, among numerous candidate proteins carrying the same non
      canonical PTS1 tripeptide, contain sufficient enhancer elements in terms of
      number, positioning and total strength to cause peroxisome targeting.

PMID- 22882978
TI  - [Peer review, a critical point of view about education].

PMID- 22882979
TI  - [The family dysfunction as a risk factor of obesity in Mexican school children].
AB  - BACKGROUND: it has been demonstrated that children obesity is a multifactorial
      disease and probably, the alteration of the family dynamic is another potential
      risk factor. The objective was to identify the association between obesity and
      family dysfunction in school children who attend to a family medicine unit.
      METHODS: case and control study at Mexican Social Security Institute in
      Guadalajara, Jalisco, Mexico. Sociodemographic factors and family dynamic of
      obese and non-obese subjects (n = 452) of six to nine years old from nuclear
      families were achieved. RESULTS: the association between family dysfunction and
      obesity was [OR = 1.63 (1.08-2.46), p = 0.01]. Area II, Identity formation, and
      area VI, Discipline and methods, showed a lower score in cases of children with
      obesity (p < 0.001 and p = 0.005, respectively). In a logistic regression model
      family dysfunction [RM 1.79 (1.19, 2.71), p = 0.005] and low literacy of mothers
      [RM 1.61 (1.06, 2.45), p = 0.02)] were risk factors for obesity in school
      children. CONCLUSIONS: the results showed an association between family
      dysfunction and obesity in school children. We suggest to consider it in the
      prevention of obesity in Mexican school children.

PMID- 22882980
TI  - [Satisfaction in the relationship between family and work of working women].
AB  - BACKGROUND: balance between work and family is difficult for women. The laboral
      participation of women has been associated with increased family dysfunction.
      This situation arises the interest in determining the existence of the
      relationship between family satisfaction and work in the working women. METHODS:
      we applied the test relations between family and work of Fernando Arias to 143
      female medical residents, 100 teachers and 100 housewives of the state of
      Sinaloa. Satisfaction was determined based on demographic characteristics.
      RESULTS: eighty-five percent felt a satisfactorily reconciliation between work
      and family roles. The teachers were better able to reconcile work and family
      relationships OR = 3.12 (1.16-8.65) p = 0.02. The more satisfied professionals
      relate on a personal level OR = 1.88 (0.99-1.01) p = 0.05 and OR = 2.92 labor
      (1.38-6.28) p = 0.03. CONCLUSIONS: there are many factors that affect settlement
      or conflict between family and work. The importance of this situation is that the
      family is the foundation of society and to achieve a fit between these two areas
      that would make families more functional.

PMID- 22882981
TI  - [Incidence of motor fluctuations in a retrospective cohort of Mexican patients
      with Parkinson's disease].
AB  - BACKGROUND: motor fluctuations induced by dopamine replacement therapy are among
      the main complications of the treatment of patients with Parkinson's disease. Our
      objective was to determine the incidence of motor fluctuations in a retrospective
      cohort of Mexican patients with Parkinson's disease. METHODS: we reviewed the
      files of 584 cases of Parkinson's disease patients treated at the National
      Institute of Neurology and Neurosurgery between 1990 and 2010. We registered the
      demographic and clinical data to analyze the disease course. RESULTS: the follow
      up was of 4736 person-years. 33.9 % of patients (n = 198) had motor fluctuations
      at some point in the evolution of the disease. The rate of person-time incidence
      was 43 cases per 1000 person-years. The daily dose of levodopa equivalents
      greater than 600 mg/d and the use of levodopa were the main risk factors for
      early development of motor fluctuations (HR 1.40 [95 % CI = 1.07 to 1.83, p <
      0.001] and HR 1.61 [95 % CI = 1.17 to 2.23, p = 0.004], respectively).
      CONCLUSIONS: the main determinants of early development of motor fluctuations are
      the levodopa equivalent daily dose and the quantity and early use of levodopa.

PMID- 22882982
TI  - [Perinatal encephalopathy sequelae identified by a neurobehavioral scale in one
      year old infants].
AB  - OBJECTIVE: to identify neurodevelopmental sequelae in one year old infants with
      perinatal encephalopathy utilizing the neurobehavioral scale named Vanedela.
      METHODS: a cohort of 75 newborns with perinatal encephalopathy was assessed with
      a neurobehavioral follow-up scale at age of 1, 4, 8 and 12 months. A distinction
      was made between functional, structural and combined encephalopathy. Two groups
      of neurodevelopmental outcome at one year were identified: with or without
      sequelae. Nonparametric statistics was used. RESULTS: infants with functional
      encephalopathy had the best scores, followed by those with structural
      encephalopathy, while infants with a combined encephalopathy had the lowest
      scores. At one year of age, the group with neurobehavioral sequelae exhibited the
      lowest scores and retarded growth. At the same age, the group with functional
      encephalopathy exhibited no neurobehavioral sequelae, and reached better scores
      and growth. CONCLUSIONS: the neurobehavioral follow-up scale is able to identify
      the neurodevelopmental sequelae at the age of one year in infants with perinatal
      encephalopathy. The application of Vanedela in the clinical field requires of
      little time, its results are trustworthy and very useful for the neurobehavioral
      follow-up assessment.

PMID- 22882983
TI  - [Current genetic issues and phenotypic variants in Kallmann syndrome].
AB  - Kallmann syndrome is characterized by hypogonadotropic hypogonadism and
      anosmia/hyposmia. The hypogonadotropic hypogonadism is due to deficiency of
      gonadotropin-releasing hormone, caused by a defect in the migration of neurons
      synthesizing gonadotropin-releasing hormone, and anosmia/hyposmia is related to
      the absence or hypoplasia of the olfactory bulb and tracts. Some patients may
      have other associated abnormalities such as renal agenesis, cleft palate, dental
      agenesis, synkinesis, shortening of metacarpal, sensory neural hearing loss and
      seizures. The aim of this paper is to present an updated review of the clinical
      and molecular basis, highlighting the relevance of knowledge of phenotypic
      variants in Kallmann syndrome.

PMID- 22882984
TI  - [Clinical research VIII. Structured review of an article].
AB  - There has been proposed several strategies to select an article under the
      assumption of quality and relevance. Mostly depend on the presence or absence of
      a number of features and others, depends of the judgment of other people.
      However, these strategies do not allow us to know the magnitude of the error
      contained within each article. And considering that there is not a perfect one,
      it is important to identify the magnitude of the error and the impact of this in
      the final result; consequently, it is necessary to develop skills that allow us
      to review a paper, identify potential errors, and generate a sense of the impact
      of it over the result. Using the information contained in Clinical Research
      Series I-VII, we have tried to show its application in a structured review of an
      article of causality beginning with the revision of the baseline, the maneuver
      and the outcome, with systematic errors (bias) generated in each section,
      followed by the appropriate of the statistical test and the sample size used, and
      finally, the clinical relevance.

PMID- 22882985
TI  - [Acute leukemia frequency observed in a reference hospital].
AB  - OBJECTIVE: to compare the frequency of acute leukemia in two periods of study in
      a reference Hospital at Mexico City. METHODS: it was an observational study.
      There were registered 250 cases with the morphology diagnostic criterion of acute
      leukemia. RESULTS: 63 cases versus 92 of acute lymphoid leukemia (ALL) and 16
      versus 79 acute myeloid leukemia (AML) of 1990-1992 versus 2008-2009 respectively
      was observed; corresponding to 62 % in total of ALL in both periods and 38 % of
      AML. The ALL was the most frequent variant (62 % versus 38 %). The median age was
      26 years, male 52 %. It showed a significant increase in the number of admissions
      in the period of 2008-2009 and acute promyelocytic leukemia also showed an
      increase (p = 0.001). CONCLUSIONS: acute leukemia is the main cause of admission,
      mortality and morbidity. Our study differs slightly from the literature; the
      leukemia that diagnostic with major frequency was the acute lymphoid leukemia
      increasing his number in the period of 2008-2009. The significant rise due to an
      increase use of new diagnostic tools such as the flow cytometry and molecular
      biology.

PMID- 22882986
TI  - [Risk factors associated with intrauterine growth restriction in newborns
      attended in a university hospital].
AB  - BACKGROUND: intrauterine growth restriction (IUGR) is related with neonatal
      morbidity and mortality. The detection and prenatal monitoring are necessary for
      an early intervention. The objective was to establish the prevalence and risk
      factors associated with intrauterine growth restriction in the university
      hospital Dr. Jose Eleuterio Gonzalez. METHODS: we performed an observational,
      cross-sectional study, during the period from May 2009 to April 2010. The sample
      was divided into two groups, asymmetrical and symmetrical IUGR. RESULTS: the
      global prevalence of IUGR was 13.5 %. We included 464 patients, 324 (70 %) with
      asymmetric IUGR and 140 (30 %) with symmetric IUGR. The maternal variables were
      not statistically significant (p = ns) between groups. We found a mean weight at
      birth higher (2548 +/- 437.33) in the symmetric IUGR group (p < 0.01), as well as
      a higher vaginal delivery rate (p < 0.05) as compared with the asymmetrical IUGR
      group. The overall mortality rate was higher in the asymmetric IUGR group (p <
      0.01). CONCLUSIONS: prevalence of IUGR in our population is higher than that
      reported in the literature; there were more preterm infants and higher mortality
      in the asymmetric group.

PMID- 22882987
TI  - [Effect of two crystalloid fluids schemes on glucose serum levels in patients
      with severe preeclampsia].
AB  - BACKGROUND: treatment of severe preeclampsia (SP) includes administration of
      crystalloid solutions to expand plasma circulating volume. Our objective was to
      compare the effects of two schemes of crystalloid solutions on glycemia in
      patients with SP. METHODS: cross-sectional study with two groups of patients:
      group A (123 patients) received a 10 % glucose solution and group B (146
      patients) received Ringer lactate solution. We compared glycemia, endogenous
      creatinine clearance (ECrCl), frequency of urinary tract infection (UTI) and
      length of hospital stay. Student t-test and Pearson correlation coefficient were
      used. RESULTS: final glycemia of group A was higher than group B (168.27 +/-
      70.85 adversus 94.20 +/- 26.63, p = 0.009). No differences were shown in ECrCl
      (group A 99.26 +/- 30.67 adversus group B, p = 0.14) or in UTI [group A 21.95 %
      (27 cases) adversus group B 18.48 % (27 cases) (p = 0.43)]. Length of hospital
      stay was different (group A 2.2 +/- 1.79 adversus group B 2.67 +/- 1.78 days, p =
      0.03). CONCLUSIONS: patients receiving a 10 % glucose solution presented
      significant hyperglycemia but not in the group receiving Ringer lactate solution.

PMID- 22882988
TI  - [Ultrasound diagnosis of an abdominal aortic aneurysm in a 52 year old woman].
AB  - The abdominal aortic aneurysm (AAA) is defined as increasing the diameter of the
      aorta in more than 50 % of its original size and the infra-renal location is the
      most common (90 %). AAA disease mainly affects older men and white smokers, and
      has a male: female ratio of 4:1, as well the diagnosis is rare in women under age
      55. Aneurysm rupture is the most common complication and cause of death in the
      general population, its etiology is unclear, but is commonly associated with
      atherosclerosis. The AAA do not exhibit rupture and  it is usually asymptomatic
      diagnosed incidentally, however, as the aneurysm grows, appears symptoms such as
      back pain, abdominal or groin pain, well as palpation of a pulse mass on
      umbilical and supra-umbilical region. Imaging study such as ultrasound and CT
      scan are the mainstay of diagnosis. We present a case of 52 years old patient
      with no history related to the diagnosis, who presented sudden and severe
      abdominal pain. She was admitted to the emergency room with a diagnosis of acute
      cholecystitis vs. acute pancreatitis. After ultrasound and CT studies, the
      diagnosis was a complicated abdominal aortic aneurysm.

PMID- 22882989
TI  - [Ovarian pregnancy. Case report and review of the subject].
AB  - A case of a 21-year-old single woman with an acute abdomen, vaginal bleeding and
      an anemic syndrome is presented. Physical examination and ultrasonography showed
      an enlarged uterus and a little mass in the right ovary, which was thought to be
      a fibroma versus pregnancy. Serum levels of chorionic gonadotropin were
      increased. Abundant black blood loose was found in the peritoneal cavity in the
      surgery performed. Through a wedge resection, a small hemorrhagic nodule was
      removed from the surface of the right ovary. Microscopic examination showed
      ovarian stroma, immature chorionic villi and intermediate extravillous
      trophoblast, which supported the diagnosis of ectopic ovarian pregnancy. This
      complication requires an opportune diagnosis, because it continues to be one of
      the leading risk factors in surgical gynecological emergencies and the first
      cause of maternal death during the first trimester of pregnancy. A brief review
      on the subject is presented.

PMID- 22882990
TI  - [Mucopolysaccharidosis I: management and follow up of three patients].
AB  - Mucopolysaccharidosis type I or mucopolisacaridosis type I is a rare genetic
      disease, with a severe and fast multiorganic damage profile and fatal prognosis
      in the early years of age. It belongs to the lysosomal storage diseases (LSD)
      group pathologies. As an LSD, mucopolisacaridosis type I is due to the lack of
      the alpha-L-iduronidase enzyme. Enzyme replacement therapy (ERT) with laronidase
      is an effective treatment choice. It is available in Mexico since 2005. In the
      Hospital UMAE 25 of the Mexican Institute of Social Security (IMSS) in Monterrey,
      Nuevo Leon, Mexico, three patients have been treated and followed since 2006,
      with a close surveillance on their clinical evolution. The ERT with laronidase is
      expensive, relatively new and with little experience in Mexico, so there is a
      real need of knowing clinical evolution as well as overall treatment efficacy
      from baseline pre-treatment stage to date. Data on physical, functional and
      biochemical changes in these patients is presented.

PMID- 22882991
TI  - [Use of rituximab in resistant thrombocytopenic purpura].
AB  - BACKGROUND: immune thrombocytopenic purpura is characterized by bleeding
      disorders associated with decreased platelet count secondary to antiplatelet
      autoantibodies. The aim of this study was to evaluate the utility of rituximab in
      the management of refractory immune thrombocytopenic purpura. CLINICAL CASES:
      four women with immune thrombocytopenic purpura unresponsiveness to standard
      therapy were evaluated in relation to clinical response and total platelets
      counts at different time intervals after rituximab administration. All four
      patients developed petechiae; two of them associated with ecchymosis, one with
      hematemesis and one more with transvaginal bleeding. The mean baseline platelet
      count was 5350/MUL; in the 60th day after the first dose of rituximab the average
      was 175 250/MUL. Complete remission was considered in three patients.
      CONCLUSIONS: rituximab is a therapeutic option for refractory inmune
      thrombocytopenic purpura. Nevertheless, more studies are needed to evaluate its
      efficacy and safety.

PMID- 22882992
TI  - [Cardiac pacemaker dysfunction due to rotation of the battery (reel syndrome)].
AB  - Reel syndrome is characterized by the rotation of permanent pacemaker generator
      on its transverse axis and electrode catheters curl around it, so this causes
      displacement of the electrodes with the loss of atrial and ventricular pacing. It
      can cause severe symptoms due to dysfunction of the pacemaker. We present three
      patient cases who after the placement of pacemaker attended by dysfunction of the
      displacement of the electrodes their clinical pictures were compatible with Reel
      syndrome.

PMID- 22882993
TI  - [Clinical guideline for diagnosis and treatment of atrial fibrillation].
AB  - Atrial fibrillation (AF) is associated with long-term increase in the incidence
      of cerebrovascular disease, heart failure and mortality. The incidence of
      ischemic stroke in patients with non-valvular atrial fibrillation averages 5 %
      per year, from two to seven more frequent than in patients without atrial
      fibrillation (AF). One in six ischemic stroke occurs in patients with AF. The
      detection and accurate diagnosis and timely therapeutic intervention have shown a
      decrease in morbidity and mortality associated with this arrhythmia. The above
      data by themselves justify the development of a management guide and care for
      these patients. The purpose of this guide is to provide health professionals
      recommendations based on the best available evidence with the intent to
      standardize actions: diagnosis and identification of patients with atrial
      fibrillation; risk stratification and treatment according to the classification
      of atrial fibrillation; identification of the risk of thromboembolism and its
      prevention; and treatment guidelines to determine which patient will require to
      be referred promptly.

PMID- 22882994
TI  - Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic
      response to metformin in type 2 diabetes.
AB  - Pharmacogenetic studies revealed that variants in genes related to the
      pharmacokinetics of metformin were associated with glucose-lowering effect of
      metformin. The aim of this study was to investigate possible associations of the
      variants in genes encoding organic cationic transporters-solute carrier family
      22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1
      (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight
      drug-naive patients with type 2 diabetes were included in the study. Genotyping
      for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was
      performed using real-time PCR with subsequent melting-curve analysis. SLC47A1
      rs2289669 genotype was significantly associated with the reduction in haemoglobin
      A1c (HbA1c) after 6 months. Twenty percentage of patients with diabetes that are
      homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison
      with the patients carrying G-allele (GG + GA: 0.55 +/- 0.09% vs. AA: 1.10 +/-
      0.18%, p = 0.018). In conclusion, the results of this study might have in future
      practical implication in personalised treatment of patients with type 2 diabetes.

PMID- 22882995
TI  - Push-out bond strength of a nano-modified mineral trioxide aggregate.
AB  - INTRODUCTION: To analyze the push-out bond strength of Angelus WMTA (Angelus
      Dental Products), a nano-modification of WMTA (Kamal Asgar Research Center) and
      Bioaggregate (Innovative Bioceramix). METHODS: Sixty 2-mm-thick root sections
      were prepared from 60 single-rooted human teeth. The dentin disks were randomly
      divided into three groups (n = 20) and filled with Angelus WMTA, Nano-WMTA, or
      Bioaggregate, respectively. Push-out bond strength values of the specimens were
      measured by a universal testing machine and examined under scanning electron
      microscope at * 40 magnification to determine the nature of the bond failure. The
      data were analyzed with a Kruskal-Wallis test. RESULTS: The greatest mean for
      push-out bond strength (138.48 +/- 11.43 MPa) was observed for the nano
      modification of WMTA. The values decreased to 110.73 +/- 11.19 and 25.64 +/- 5.27
      MPa for Angelus WMTA and Bioaggregate, respectively. There were significant
      differences between the groups (P < 0.001). Inspection of the samples revealed
      the bond failure to be predominantly adhesive type except for the nano
      modification group, as some samples also exhibited cohesive failures.
      CONCLUSIONS: It is concluded that the force needed for the displacement of the
      nano-modification of WMTA (NWMTA) was significantly higher than for Angelus WMTA
      and Bioaggregate.

PMID- 22882996
TI  - Effect of 3-alkylpyridine marine alkaloid analogues in Leishmania species related
      to American cutaneous leishmaniasis.
AB  - A series of oxygenated analogues of marine 3-alkylpyridine alkaloids were
      synthesized, and their leishmanicidal activity was assayed. All compounds were
      prepared from 3-pyridinepropanol in few steps and in good yields. The key step
      for the synthesis of these compounds was a classic Williamson etherification
      under phase-transfer conditions. Besides toxicity in peritoneal macrophages, the
      compounds exhibited a significant leishmanicidal activity. Of twelve compounds
      tested, five showed a strong leishmanicidal activity against promastigote forms
      of Leishmania amazonensis and L. braziliensis with IC50 below 10 MUm. Compounds
      11, 14, 15, and 16 showed a strong leishmanicidal activity on intracellular
      amastigotes (IC50 values of 2.78; 0.27; 1.03, and 1.33 MUm, respectively), which
      is unlikely to be owing to the activation of nitric oxide production by
      macrophages.

PMID- 22882999
TI  - [How to balance the antiretrovirus drugs and cost in China].

PMID- 22882997
TI  - Population-based analyses of Giardia duodenalis is consistent with the clonal
      assemblage structure.
AB  - BACKGROUND: Giardia duodenalis is a common protozoan parasite of humans and
      animals. Genetic characterization of single loci indicates the existence of eight
      groups called assemblages, which differ in their host distribution. Molecular
      analyses challenged the idea that G. duodenalis is a strictly clonal diplomonad
      by providing evidence of recombination within and between assemblages.
      Particularly, inter-assemblage recombination events would complicate the
      interpretation of multi-locus genotyping data from field isolates: where is a
      host infected with multiple Giardia genotypes or with a single, recombined
      Giardia genotype. METHODS: Population genetic analyses on the single and multiple
      locus level on an extensive dataset of G. duodenalis isolates from humans and
      animals were performed. RESULTS: Our analyses indicate that recombination between
      isolates from different assemblages are apparently very rare or absent in the
      natural population of Giardia duodenalis. At the multi-locus level, our
      statistical analyses are more congruent with clonal reproduction and can equally
      well be explained with the presence of multiple G. duodenalis genotypes within
      one field isolate. CONCLUSIONS: We conclude that recombination between G.
      duodenalis assemblages is either very rare or absent. Recombination between
      genotypes from the same assemblage and genetic exchange between the nuclei of a
      single cyst needs further investigation.

PMID- 22883000
TI  - [Influence of long-term highly active antiretroviral therapy on bone mineral
      density in HIV/AIDS patients].
AB  - OBJECTIVE: To evaluate the influence of highly active antiretroviral therapy
      (HAART) on bone mineral density (BMD) in HIV/AIDS patients and correlating
      clinical factors. METHODS: 149 HIV patients were divided into 3 groups:untreated
      group with 41 patients, HAART for 1-2 years group with 60 patients, HAART over 5
      years group with 48 patients; 20 healthy individuals included as a control group.
      BMD-T score and BMD-Z score were measured by dual-energy X-ray absorptiometry
      (DXA). RESULTS: BMD-Z score of right hip was significantly lower in HAART over 5
      years group (0.16 +/- 0.82) than untreated group (0.61 +/- 1.09) (P = 0.039). BMD
      Z score of right femoral neck was significantly lower in HAART over 5 years group
      (-0.002 +/- 0.87) than untreated group (0.55 +/- 1.08) (P = 0.012). BMD-Z score
      of HAART for 1-2 years group was not significantly decreased. BMD-Z score of
      right hip and right femoral neck were correlated negatively with HAART duration.
      The incidence of osteopenia/osteoporosis in HAART for 1 - 2 years group (31.7%)
      and HAART over 5 years group (31.3%) were significantly higher than untreated
      group (12.2%) (P < 0.05). Body weight was revealed as a risk factor of
      osteopenia/osteoporosis. CONCLUSION: BMD of right hip and right femur neck were
      significantly lower in HAART over 5 years group. The incidence of
      osteopenia/osteoporosis were significantly higher in patients receiving HAART.
      BMD were correlated negatively with HAART duration. Patients in long-term HAART
      combined with risk factors such as old age or lower body weight should be checked
      by DXA regularly.

PMID- 22882998
TI  - Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA
      increases activation of secondary metabolite production.
AB  - Regulation of secondary metabolite (SM) gene clusters in Aspergillus nidulans has
      been shown to occur through cluster-specific transcription factors or through
      global regulators of chromatin structure such as histone methyltransferases,
      histone deacetylases, or the putative methyltransferase LaeA. A multicopy
      suppressor screen for genes capable of returning SM production to the SM
      deficient DeltalaeA mutant resulted in identification of the essential histone
      acetyltransferase EsaA, able to complement an esa1 deletion in Saccharomyces
      cereviseae. Here we report that EsaA plays a novel role in SM cluster activation
      through histone 4 lysine 12 (H4K12) acetylation in four examined SM gene clusters
      (sterigmatocystin, penicillin, terrequinone and orsellinic acid), in contrast to
      no increase in H4K12 acetylation of the housekeeping tubA promoter. This
      augmented SM cluster acetylation requires LaeA for full effect and correlates
      with both increased transcript levels and metabolite production relative to wild
      type. H4K12 levels may thus represent a unique indicator of relative production
      potential, notably of SMs.

PMID- 22883001
TI  - [Association between amino acid mutations in Gag protein and human leukocyte
      antigen class I alleles in human immunodeficiency virus-1 B' infected Han Chinese
      people].
AB  - OBJECTIVE: To explore the human leukocyte antigen (HLA)-associated mutations in
      Gag protein of B' clade (human immunodeficiency virus-1) HIV-1 infected Han
      Chinese people and evaluate the impact of HLA associated Gag mutations on the
      disease progression of HIV infection. METHODS: A total of 95 B' clade HIV-1
      infected Han Chinese cases were recruited. The gag sequences were amplified from
      viral RNA and sequenced directly. HLA-I genotypes were detected with the assay of
      polymerase chain reaction-sequence specific primer (PCR-SSP). HLA-associated
      mutations were identified and the relationships between HLA-associated mutations
      and CD4+ T cell counts or plasma viral loads analyzed. RESULTS: Forty-seven kinds
      of mutations at 28 sites (15, 18, 26, 30, 34, 46, 62, 67, 81, 84, 90, 102, 118,
      121, 122, 125, 146, 147, 173, 176, 252, 357, 374, 376, 437, 470, 471, 478) of Gag
      protein were significantly associated with particular HLA class I allelotypes (P
      < 0.05). Among which, 9 sites (26, 30, 81, 84, 125, 146, 147, 357, 437) were
      located within 13 known cytotoxic T-lymphocyte (CTL) epitopes or flanking
      regions. The number of HLA-associated mutations was significantly associated with
      both CD4 T cell counts (r = -0.318, P = 0.002) and viral loads (r = 0.360, P =
      0.003). CONCLUSION: HLA-associated mutations may have a significant impact on HIV
      disease progression in B' clade HIV-1 infected Han Chinese population.

PMID- 22883002
TI  - [Primary drug resistance of HIV-1 infected men who have sex with men in Shenzhen,
      China].
AB  - OBJECTIVE: To evaluate the status of drug resistance among treat-naive HIV-1
      infected men who have sex with men (MSM) in Shenzhen during the period of 2008 -
      2010. METHODS: Plasma samples of 227 treatment-naive HIV-1 infected MSM were
      collected in Shenzhen. HIV-1 pol genes (RT and PR) were amplified by nested
      polymerase chain reaction (PCR) from RNA. Phylogenetic and drug resistance
      analyses were performed on the nucleotide sequence data. RESULTS: A total of 164
      pol gene sequences were amplified. The prevalence of primary genotypic drug
      resistance was 14.6%. The overall prevalence of drug-resistant mutations was
      22.6%, corresponding to 8.54% for protease inhibitors (PI) minor drug resistance
      mutation, 1.22% for nucleotide reverse transcriptase inhibitors (NRTI) drug
      resistance mutation and 13.41% for non-nucleotide reverse transcriptase
      inhibitors (NNRTI) drug resistance mutation. The prevalence of drug-resistant
      mutations was 30.88% for CRF01_AE strain and 19.23% for B strain. CONCLUSION: The
      prevalence of drug resistance is relatively moderate in the treat-naive HIV-1
      infected MSM in Shenzhen. The prevalence of drug-resistant HIV-1 among MSM in
      Shenzhen should raise a high alert.

PMID- 22883003
TI  - [Response to thymectomy and analysis of influencing factors in the treatment of
      children with myasthenia gravis].
AB  - OBJECTIVE: To evaluate the efficacy of thymectomy and relevant influencing
      factors in the treatment of children with myasthenia gravis through a long-term
      follow-up. METHODS: The clinical records of 59 patients undergoing expanded
      thymectomy for the treatment of myasthenia gravis (MG) between January 2003 and
      August 2009 were reviewed retrospectively. Their postoperative outcomes were
      categorized into complete stable remission (CSR), pharmacological remission (PR),
      improvement, no change and deterioration (including mortality). RESULTS: During a
      median follow-up period of 35 months, none of them died or deteriorated
      clinically among 53 patients with a postoperative follow-up. The overall
      remission rate was 69.8% and the effective rate 90.6%. No symptomatic relapse
      occurred among 16 patients in CSR. None of the ocular patients progressed to
      generalized MG while 16 thymectomized generalized MG developed from ocular MG.
      Both univariate and logistic regression analyses revealed that the preoperative
      duration of illness influenced the surgical curative effect (P < 0.05). Survival
      analysis indicated that the rates of overall remission were 56% or 88% at 24
      months and 42% or 75% at 48 months among ocular MG and generalized MG
      respectively. According to Log-rank analysis, no difference in remission existed
      between two types of MG. CONCLUSION: Thymectomy is an effective and safe
      treatment in selected MG children, especially in those with a shorter illness
      duration.

PMID- 22883004
TI  - [Efficacy and safety of the combined therapy of valproic acid and lamotrigine for
      epileptics].
AB  - OBJECTIVE: To explore the efficacy and safety of the combined therapy of valproic
      acid (VPA) and lamotrigine (LTG) for various types of epilepsy. METHODS: The
      patients were recruited from the epilepsy center at Affiliated Tongji Hospital,
      Tongji Medical College, Huazhong Science & Technology University from January
      2009 to September 2011. They were randomly selected through a number chart and
      divided into two groups: child group and adult group. The prospective follow-up
      study lasted for one year to examine the long-term efficacy and safety of
      combined therapy. Seizure frequency was recorded at Months 3, 6 and 12. The
      changes of seizure frequency were analyzed to calculate the 50% response rate,
      75% response rate and seizure-free rate. All side effects during therapy were
      recorded. The correlation of efficacy with seizure type was also examined.
      Statistical analysis was performed through t test, variance analysis and chi(2)
      test. RESULTS: Among a total of 134 patients, 10 of them withdrew. At Months 3, 6
      and 12, as compared with baseline, the average reduction rate of seizure
      frequency per month was 56%, 62%, 70% in child group versus 74%, 82%, 85% in
      adult group (P < 0.05). Adult group was better than child group. At Month 3, 50%
      response rate, 75% response rate and seizure-free rate was 70.97% - 35.48% in
      child group versus 83.87% - 43.01% in adult group. When compared at Months 3, 6
      and 12, 50% response rate, 75% response rate and seizure-free rate showed no
      statistical difference (P > 0.05). The worse outcomes occurred more frequently in
      the patients with complex partial seizure (CPS) and than those with simple
      partial seizure (SPS) and generalized seizure GS (P < 0.05). Rash was the major
      side effect for withdrawal. CONCLUSION: The co-medication of VPA and LTG is both
      effective and safe for all epileptic types, especially for SPS and GS. And the
      efficacy may last for up to one year. Combined therapy shows excellent safety.

PMID- 22883005
TI  - [Stenting treatment of venous sinus stenosis for intractable pulsatile tinnitus].
AB  - OBJECTIVE: To evaluate the application, effectiveness and safety of stenting in
      venous sinus stenosis for intractable pulsatile tinnitus via endovascular
      treatment. METHODS: From January 2010 to July 2011, 12 cases with intractable
      pulsatile tinnitus originating from cerebral venous sinus stenosis underwent
      stenting treatment. All of them were diagnosed by digital subtraction angiography
      (DSA). There was ipsilateral stenosis in junction segment of sigmoid and
      transverse sinuses. The diverticulum of sigmoid sinus was found in 6 cases.
      Eleven patients underwent stenting placement and angioplasty for venous sinus
      stenosis. RESULTS: All pulsatile tinnitus symptoms disappeared immediately after
      stenting. No related complication was found during stenting and over a follow-up
      period of 3 - 22 months. There was no recurrence of pulsatile tinnitus.
      CONCLUSIONS: Stent placement is a safe and effective procedure for pulsatile
      tinnitus with cerebral venous sinus stenosis.

PMID- 22883007
TI  - [Evaluations of puberty sexual development in girls by intraluminal ultrasound].
AB  - OBJECTIVE: To assess the significance of intraluminal ultrasound in the diagnosis
      of developmental status and treatment effect in normal and idiopathic precocious
      puberty (ICPP) girls. METHODS: Endorectal ultrasonography was used to measure the
      parameters of uterine length, width, thickness, cervix length, ovarian volume and
      maximum follicular length in normal girls and compare their differences between
      pre- and post-treatment by gonadotropin-releasing hormone analogues (GnRHa) in
      idiopathic precocious puberty girls. RESULTS: The ultrasonic parameters of uterus
      and ovary in normal girls significantly increased in average 9-year-old girls
      (1.87 +/- 0.58) ml of uterine volume in 9-year-old group vs (1.03 +/- 0.24) ml in
      7-year-old group; ovarian volume (3.01 +/- 2.73) ml of uterine volume in 9-year
      old group vs 0.98 +/- 0.36 ml in 7-year-old group. They were much greater in ICPP
      girls and decreased significantly at post-treatment, (1.16 +/- 0.19) ml of uterus
      volume pre-treatment vs (1.02 +/- 0.15) ml post-treatment; (2.11 +/- 0.48) ml of
      ovarian volume pre-treatment, (1.72 +/- 0.55) ml post-treatment; (1.36 +/- 0.25)
      cm of the biggest follicular diameter pre-treatment, (1.16 +/- 0.36) cm post
      treatment. CONCLUSION: Endosonography is an important tool of evaluating the
      development status and treatment effect in normal and ICPP girls.

PMID- 22883006
TI  - [Correlation of H-type hypertension and prognosis of ischemic stroke].
AB  - OBJECTIVE: To examine the correlation between hypertension with
      hyperhomocysteinemia and prognosis of ischemic stroke. METHODS: A total of 634
      patients with acute ischemic stroke confirmed by computed tomography or magnetic
      resonance imaging were recruited at Department of Neurology, First Affiliated
      Hospital, Zhengzhou University from January 1, 2007 to May 30, 2010. Their NIHSS
      (National Institute of Health Stroke Scale) scores were evaluated on admission.
      And their baseline profiles and probable prognostic factors were recorded.
      Recovery was assessed by modified Rankin score (MRS) during a 6-month follow-up.
      Multivariate Logistic regression was performed for statistical analysis. RESULTS:
      Among them, 32 became lost to follow-up. There were 197 females (32.7%) and 405
      males (67.3%) with an average age of (59 +/- 13) years (range: 19 - 92). The
      average level of homocysteine was (19 +/- 11) umol/L. There were 343 (57%)
      patients with hypertension and MRS >= 3 was in 145 (31%) patients. Logistic
      regression analysis showed that significant correlations existed between H-type
      hypertension and 6-month MRS (P = 0.012, OR = 2.566, 95%CI: 1.299 - 5.357) when
      homocysteine >= 15 umol/L was defined for hyperhomocysteinemia. And there was a
      total sum of interaction between hypertension and hyperhomocysteinemia. The
      parameters of relative excess risk of interaction (RERI), attributable proportion
      due to interaction (AP) and synergy index (S) were 0.683, 26.61% and 1.59
      respectively. Other parameters with significant prognostic correlations included
      age, history of stroke, NIHSS score on admission and diastolic blood pressure on
      admission. CONCLUSION: At the homocysteine level of >= 15 umol/L, H-type
      hypertension and 6-month MRS have significant correlations. And H-type
      hypertension is a risk factor for the prognosis of ischemic stroke. When
      hypertension and hyperhomocysteinemia coexist, there is a total sum of
      interaction.

PMID- 22883008
TI  - [Diagnosis and surgical treatment of pulmonary sclerosing hemangioma].
AB  - OBJECTIVE: As a rare benign lung tumor, pulmonary sclerosing hemangioma (PSH)
      occurs predominantly in Asian women in their fifth and sixth decades of life. PSH
      is considered to be evolved from primitive undifferentiated respiratory
      epithelium. In this study, we summarized our experience in 89 cases of PSH.
      METHOD: There were a total of 89 patients who received surgical resection and
      were histopathologically diagnosed as PSH during the period January 2001 to
      December 2010 in department of thoracic surgery, Cancer Institute and Hospital,
      Peking Union Medical College and Chinese Academy of Medical Sciences. The
      clinical data of these patients including symptoms, disease courses, image
      characteristics and surgical procedures were collected and reviewed
      retrospectively. RESULTS: The PSHs were most frequently (50.6%) found in the
      patients aged 41 to 60 years with a median age of 51 years (range: 24 - 71), and
      the sex ratio (male/female) was approximately 1:7 in this series. In the 89
      patients, 53 (59.6%) were asymptomatic while the other 36 (40.4%) had some non
      special symptoms such as cough (30.3%), hemoptysis (24.7%). There were only 3
      cases (3.4%) with multiple PSHs, 4 cases (4.5%) combined with synchronous primary
      lung cancer, and 13 cases (14.6%) with lesions located in the hilar region. The
      median diameter of the 92 lesions was 2.3 cm (range: 0.3 - 6.0 cm), of which 38%
      located in the right lower lobe and 26.1% in the right middle lobe, and only
      about 1/3 were assumed as PSHs preoperatively based on CT imaging. One of the
      five patients who underwent PET-CT scan had been misdiagnosed as malignant. Of
      the 92 lesions, 47 were resected by enucleation, 29 by wedge resection, 14 by
      lobectomy, and 2 by pneumonectomy. CONCLUSION: PSH frequently occurs in the
      middle-aged women. Most individuals with PSH are asymptomatic or have some non
      specific symptoms. Their lesions are usually found accidentally by chest imaging.
      Although PSH often shows typical imaging characteristics of benign neoplasm of
      the lung, it is difficult to establish a defined pathological diagnosis
      preoperatively. The significant error or deferred rate of intraoperative frozen
      section evaluation for PSH may result in some unnecessarily extensive surgical
      procedures. The complete surgical resection is considered the only effective
      treatment for PSH, and the normal pulmonary tissue should be reserved as
      possible.

PMID- 22883009
TI  - [A prospective cohort study of the risk factors of emergence agitation in
      pediatric after general anesthesia].
AB  - OBJECTIVE: To evaluate risk factors associated with emergence agitation (EA) in
      pediatrics after general anesthesia. METHODS: A prospective cohort study was
      conducted in 268 pediatric patients aged 2-9 years, who received general
      anesthesia for various operative procedures in our hospital between January 2008
      and October 2011. The incidence of EA was assessed. Difficult parental-separation
      behavior, pharmacologic and non-pharmacologic interventions, and adverse events
      were also recorded. Univariate and multivariate analysis were used to determine
      the factors associated with EA. A p-value of less than 0.05 was considered
      significant. RESULTS: One hundred and sixteen children (43.3%) had EA, with an
      average duration of 9.1 +/- 6.6 minutes. EA associated with adverse events
      occurred in 35 agitated children (30.2%). From univariate analysis, factors
      associated with EA were difficult parental-separation behavior, preschool age (2 
      5 years), and general anesthesia with sevoflurane. However, difficult parental
      separation behavior, and preschool age were the only factors significantly
      associated with EA in the multiple Logistic regression analysis with OR = 3.091
      (95%CI: 1.688, 5.465, P < 0.01) and OR = 1.965 (95%CI: 1.112, 3.318, P = 0.024),
      respectively. CONCLUSION: The present study indicated that the incidence of EA
      was high in PACU. Preschool children and difficult parental-separation behavior
      were the predictive factors of emergence agitation.

PMID- 22883010
TI  - [Biomechanical study of atlantoaxial fixation for transverse ligament injury
      leading to atlantoaxial instability].
AB  - OBJECTIVE: To explore the three-dimensional movement of atlantoaxial joint,
      complete transverse ligament and cracked transverse ligament after posterior
      atlantoaxial fixation. METHODS: The fresh upper cervical cadaveric specimens were
      collected from 6 males dead from active craniocerebral injury. The average age
      was 39.7 years old (range: 26 - 57). The specimens were divided into 3 groups of
      intact (Group I), transverse ligament cracked (Group D) and posterior
      atlantoaxial fixation (Group F). They were tested consecutively. RESULTS: The
      range of sagittal movement increased when the transverse ligament became cracked.
      And it had significant difference compared with the Group I (P < 0.05). But the
      ranges of lateral flexion and rotation showed no significant difference. When
      posterior atlantoaxial fixation was performed, all three-dimensional movements
      decreased. And significant differences existed as compared with Group I (P <
      0.05). CONCLUSION: Under normal conditions, the main movement of atlantoaxial
      joint is rotation with lesser sagittal movement and lest lateral flexion. The
      range of sagittal movement increases significantly when transverse ligament is
      cracked (P < 0.05), especially so for anteflexion movement. The increase of
      lateral flexion and rotation has no significant difference compared with Group I.
      When posterior atlantoaxial Fixation is performed, all three-dimensional
      movements decrease significantly as compared with Group I (P < 0.05), especially
      loss of rotation function.

PMID- 22883011
TI  - [Influences of clinical symptoms on the selection of surgical options for adult
      degenerative scoliosis].
AB  - OBJECTIVE: To retrospectively analyze the interactions between the clinical
      symptoms and surgical options and evaluate the surgical efficacies for adult
      degenerative scoliosis (DS). METHODS: A total of 35 adult DS patients underwent
      operations at Tianjin hospital from May 1996 to December 2008. There were 23
      females and 12 males with a mean age of 59.1 years (range: 45 - 74). Clinical
      symptoms, physical examinations and radiological findings for all patients were
      recorded at different stages, at 1 week, 3 months, 6 months, 1 year post
      operation and per year respectively. According to different surgical options,
      they were classified into 3 groups: A: limited decompression; B: selective
      decompression & short-segment fusion; C: selective decompression & long-segment
      correction & fusion. RESULTS: All patients had complete records with a mean
      follow-up period of 42.4 months (range: 24 - 168). Firstly, 9 patients in group A
      had no complaint of a low-back pain at pre-operation. The average coronal Cobb's
      angles were 15.6 +/- 2.3 degrees  at pre-operation and 17.1 +/- 3.3 degrees  at
      the latest follow-up. The radicular symptoms became greatly relieved at 1 year.
      Three cases complained of the aggravation of back pain. Secondly, 15 patients in
      group B mainly complained of a low-back pain at pre-operation. It was combined
      with lower-limb radiation pain in 6 patients and nerve claudication in 9 cases.
      The average coronal Cobb's angles were 14.1 +/- 4.6 degrees  at pre-operation and
      24.4 +/- 6.7 degrees  at the latest follow-up. However, 12 patients experienced
      the progression of scoliosis. Thirdly, 11 patients in group C experienced a low
      back pain at pre-operation while 5 cases with lower-limb radiation pain and 6
      with claudication. The mean coronal Cobb's angles were 22.3 +/- 9.2 degrees  at
      pre-operation and 12.2 +/- 4.7 degrees  at the latest follow-up. Among 4 patients
      with residual pains, none required revision. CONCLUSIONS: For the DS patients, it
      is quite important for the surgical options to comprehensively analyze the
      neurological signs, imaging data and clinical symptoms. However, the fusion end
      vertebrae should always avoid the vicinity or apex of curve if the short-segment
      fusion is selected.

PMID- 22883012
TI  - [Turning over rough surface of aponeurosis of gastrocnemius for repairing freshly
      torn Achilles tendon].
AB  - OBJECTIVE: To evaluate the therapeutic outcomes of freshly torn Achilles tendon
      by turning over aponeurosis of gastrocnemius and holding its rough surface to
      contact with sutured tendons. METHODS: Thirty-two patients with torn Achilles
      tendon received surgeries at our department. There were 20 males and 12 females
      with an age range of 22 - 45 years. All patients were injured during movement.
      The surgical techniques involved applying medial straight incision of tendon
      about 5 cm, under the help of long tractors, turning over aponeurosis of
      gastrocnemius and holding its rough surface to contact with sutured tendons. All
      patients were motivated to accept early motion exercises after surgery. The
      follow-up was carried out during May 2007 to January 2010 with an average period
      of 18 months. Based upon the Arner Lindholm score, their therapeutic outcomes
      were evaluated. RESULTS: Incisions were healing well in all patients. All
      patients removed long plaster and changed into short plaster when they received
      operation for 3 weeks. After 6 weeks, plaster was removed and they began to
      exercise movement of ankle. At Week 8, their ankle functions were close to
      normal. At Week 12, they could jog. The final outcomes were as follows: excellent
      (n = 24), good (n = 6) and poor (n = 2). The excellent rate was over 93.75%.
      CONCLUSION: Turning over aponeurosis of gastrocnemius and holding its rough
      surface to contact with sutured tendons is an excellent therapeutic method for
      freshly torn Achilles tendon so that the patients may be motivated to execute
      early motion exercises. Early motion exercise is essential for an earlier
      recovery of postoperative function.

PMID- 22883013
TI  - [Comparative study of clinical effects of VCu IUD and TCu380A IUD were used on
      women who once been done cesarean section].
AB  - OBJECTIVE: To study and compare the clinical efficacies and characteristics of
      VCu intrauterine device (IUD) and TCu380A IUD in childbearing-aged women with
      previous cesarean section so as to provide rationales for an informed choice of
      contraceptive methods. METHODS: According to their physical status, a total of
      400 women undergoing previous cesarean section were randomly provided VCu IUD and
      TCu380A IUD from February 2008 to August 2009. These healthy women were had no
      contraindication to IUD. The volunteers required voluntarily the placement of
      IUD. Then all of them were followed up for 3, 6 and 12 months. RESULTS: At Month
      12, the pregnant rate with IUD in situ of VCu and TCu380A IUD were 1.02% and
      4.64%, expulsion rate 0 and 3.1% and withdrawing rate 1.02% and 4.13%
      respectively. The pregnant rate was significantly different (P < 0.05); VCu
      showed a lower expulsion and withdrawing rate than that in TCu380A (P < 0.05);
      the continuation rate of VCu was higher than that of TCu380A (P < 0.05).
      CONCLUSION: VCu offers a better efficacy of contraception with a lower expulsion
      and withdrawing rate, a higher continuation rate and a simpler placement method.

PMID- 22883014
TI  - [Reasonable anesthetic management for correction of Ebstein's anomaly].
AB  - OBJECTIVE: To summarize the experience in anesthetic management for correction of
      Ebstein's anomaly. METHODS: A total of 79 patients with Ebstein's anomaly who
      underwent surgical repair in our hospital during the time from March 2004 to
      September 2010 were retrospectively summarized for their anesthetic management.
      Anesthesia was done for the patients undergoing correction of Ebstein's anomaly.
      The adults patients were premedicated with intramuscular morphine 0.2 mg/kg and
      diazepam 0.05 mg/kg. The children patients were premedicated with intramuscular
      ketamine 5 - 8 mg/kg and atropine 0.05 - 0.20 mg. General anesthesia was induced
      with midazolam 0.1 - 0.2 mg/kg, etomidate 0.2 - 0.3 mg/kg, sulfentanil 1.0 - 1.5
      ug/kg, pipecuronium or vecuronium 0.1 - 0.2 mg/kg, and maintained with isoflurane
      inhalation and intermittent iv. midazolam and sulfentanil. RESULTS: Anesthetic
      course was smooth. The symptom in all cases was improved significantly after
      operation. No patients died during perioperative period. CONCLUSION: The key
      points for the anesthetic management of Ebstein's anomaly include precise
      preoperative evaluation, steady hemodynamic, proper maintenance of suitable
      pulmonary vascular resistance and cardiac function.

PMID- 22883015
TI  - [Expression of delta subunit of gamma-aminobutyric acid A in hippocampus induced
      by insular-kindled rats].
AB  - OBJECTIVE: To explore the expression of delta subunit-containing gamma
      aminobutyric acid(A) (GABA)(A) receptors in insular electrical kindled rats and
      analyze the significance of the findings. METHODS: A total of 48 male Sprague
      Dawley rats were divided randomly into 3 groups: kindled, sham-operated and
      control. Kindled group: chronic insular electrical kindled models of rats
      established by electrical stimulation. Sham-operated group: the same method of
      the kindled group without electrical stimulation. CONTROL GROUP: without surgery.
      The number of hippocampal neurons of rat epilepsy, sham-operated and control
      groups were detected by Nissl staining. The hippocampal expressions of delta
      subunit of these groups were tested by immunohistochemistry. The mRNA of delta
      subunit of hippocampus of these groups was detected by quantitative-polymerase
      chain reaction (q-PCR). RESULTS: The findings of Nissl staining showed that there
      was no significant difference of the number of hippocampal neurons between
      epileptic and normal rats (P > 0.05). The findings of q-PCR showed that mRNA of
      delta subunit of the hippocampus of sham-operated and control groups represented
      much more than that of kindled group at Day 7 post-kindling (P < 0.01). The
      findings of immunohistochemistry showed that the hippocampal expression of delta
      subunit of sham-operated and control groups represented much more than that of
      kindled group at Day 7 post-kindling (P < 0.01). CONCLUSION: The hippocampal
      expression of delta subunit-containing GABA(A) receptors decreases in insular
      epilepsy. It may play an important role in the occurrence and development of
      insular epilepsy.

PMID- 22883016
TI  - [Roles and mechanisms of E2F-1 and PAC1 in signaling oxidative stress-induced
      apoptosis of Saos-2 cells].
AB  - OBJECTIVE: To explore the roles and mechanisms of E2F-1 and PAC1 in signaling
      apoptosis of Saos-2 cells under oxidative stress. METHODS: siRNAs were used to
      construct the cell clones of expressing siE2F-1 and siPAC1. E2F-1/PAC1-mediated
      induction of apoptotic cell death in response to H2O2 were examined by trypan
      blue exclusion and the expression levels of related target factors detected by
      Western blot. RESULTS: The cell viabilities of Saos-2/siE2F-1 and Saos-2/siPAC1
      increased markedly comparing with the control cells after the treatment of H2O2.
      And the expression level of p-ERK1/2 was higher than that of the control cells.
      CONCLUSIONS: The pathway of E2F-1/PAC1/MAPKase is a specific cascade for
      apoptotic signaling.

PMID- 22883017
TI  - Outpatient urological procedures in antibiotic-naive patients with bladder cancer
      with asymptomatic bacteriuria.
AB  - Study Type - Therapy (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? Urine culture and antibiotics are usually
      given before outpatient urological procedures, namely cystoscopy or intravesical
      BCG therapy. Injudicious use of antibiotics promotes multidrug bacterial
      resistance. Pretreatment antibacterial therapy may not be necessary before
      outpatient urological procedures in patients with bladder cancer. Such strategy
      facilitates timely intervention and avoids antibiotic resistance. OBJECTIVES: * 
      To investigate the frequency of infectious complications after intravesical BCG
      therapy or cystoscopy in antibiotic-naive patients with bladder tumours who have
      asymptomatic bacteriuria. *  The aim was to avoid antibiotics in infected
      patients undergoing these common outpatient urological procedures. METHODS: *  A
      total of 354 patients received induction BCG therapy and another 663 patients
      underwent cystoscopy after submitting a voided urine sample for culture. They
      received no antibiotics before or after the procedure. *  Significant bacteriuria
      was defined as >10(4) or >10(5) colony-forming units per millilitre with a single
      organism. *  The patients were followed for 3 months for onset of febrile UTI,
      defined as dysuria and fever >38  degrees C requiring antibiotics. RESULTS: * 
      Ninety BCG-treated patients (25%) and 114 cystoscopy patients (17%) had
      bacteriuria. *  After BCG therapy, two patients with infected urine (2.2%) and
      three with sterile cultures (1.1%) had febrile UTIs (P= 0.17). *  After
      cystoscopy, four infected patients (3.5%) and five uninfected patients (1%) had
      febrile UTIs (P= 0.08). *  All UTIs resolved within 24 h with oral antibiotics,
      and none of the patients was admitted for bacterial sepsis. CONCLUSIONS: * 
      Antibacterial prophylaxis before intravesical BCG therapy or outpatient
      cystoscopy does not appear to be necessary in patients with asymptomatic
      bacteriuria. *  Such strategy avoids overuse of antibiotics, reducing drug
      resistant bacterial infections.

PMID- 22883018
TI  - Hic-5 affects proliferation, migration and invasion of B16 murine melanoma cells.
AB  - Hic-5 is a shuttling protein between the cell membrane and the nucleus which
      functions as a focal adhesion adaptor protein and a nuclear receptor coactivator.
      Although several studies have shown its involvement in other types of cancer, the
      role of Hic-5 in melanoma is unknown. Herein, we show for the first time that Hic
      5 is expressed in B16-F1 murine melanoma cells. To determine its function in
      melanoma cells, we used shRNA-mediated RNA interference and established stable
      clones with down-regulated Hic-5 expression. These clones had impaired growth and
      metastatic potential compared with controls in vivo, which correlated with
      decreased proliferation, migration and invasion in vitro. Moreover, silencing of
      Hic-5 expression in B16-F1 activated RhoA with an amoeboid phenotypic change,
      indicating that Hic-5 is a key regulator of B16-F1 metastasis in the context of
      Rho-dependent motility. These results provide new evidence that Hic-5 is a
      possible molecular target for treatment of melanoma.

PMID- 22883019
TI  - Case conferences as interventions dealing with the challenging behavior of people
      with dementia in nursing homes: a systematic review.
AB  - BACKGROUND: Challenging behaviors such as aggression, screaming, and apathy are
      often encountered when caring for people with dementia in nursing homes. In this
      context, a case conference is often recommended for healthcare professionals as
      an effective instrument to improve the quality of care. However, the subject case
      conference has not had great consideration in scientific literature. The aim of
      this review is to describe the effects of case conferences on people with
      dementia and challenging behavior and the staff in nursing homes. METHODS: A
      search of intervention studies in nursing homes in the German or English language
      was performed in the following databases: Medline, Cinahl, PsycINFO, Cochrane
      library, Embase, and Google Scholar. The selection and the methodological quality
      of the studies were assessed independently by two authors. The results were
      summarized and compared based on categories such as study quality or outcomes.
      RESULTS: Seven of 432 studies were included in the review. A total of four of
      seven studies showed a reduction in the challenging behavior of people with
      dementia, and five showed an influence on the competence, attitudes, and job
      satisfaction of the staff. However, due to the middle-range quality of several
      studies, the methodological heterogeneity and differences in the interventions,
      the results must be interpreted with caution. CONCLUSIONS: In summary, little
      evidence exists for the positive effects of case conferences in the care of
      people with dementia. This review highlights the need for methodologically well
      designed intervention studies to provide conclusive evidence of the effects of
      case conferences.

PMID- 22883020
TI  - Efficiency and safety of inhalative sedation with sevoflurane in comparison to an
      intravenous sedation concept with propofol in intensive care patients: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: State of the art sedation concepts on intensive care units (ICU)
      favor propofol for a time period of up to 72 h and midazolam for long-term
      sedation. However, intravenous sedation is associated with complications such as
      development of tolerance, insufficient sedation quality, gastrointestinal
      paralysis, and withdrawal symptoms including cognitive deficits. Therefore, we
      aimed to investigate whether sevoflurane as a volatile anesthetic technically
      implemented by the anesthetic-conserving device (ACD) may provide advantages
      regarding 'weaning time', efficiency, and patient's safety when compared to
      standard intravenous sedation employing propofol. METHOD/DESIGN: This currently
      ongoing trial is designed as a two-armed, monocentric, randomized prospective
      phase II study including intubated intensive care patients with an expected
      necessity for sedation exceeding 48 h. Patients are randomly assigned to either
      receive intravenous sedation with propofol or sevoflurane employing the ACD.
      Primary endpoint is the comparison of the 'weaning time' defined as the time
      required from discontinuation of the sedating agent until sufficient spontaneous
      breathing occurs. Moreover, sedation depth evaluated by Richmond Agitation
      Sedation Scale and parameters of patient's safety (that is, vital signs,
      laboratory monitoring of organ function) as well as the duration of mechanical
      ventilation and overall stay on the ICU are analyzed and compared. An intention
      to-treat analysis will be carried out with all patients for whom it will be
      possible to define a wake-up time. In addition, a per-protocol analysis is
      envisaged. Completion of patient recruitment is expected by the end of 2012.
      DISCUSSION: This clinical study is designed to evaluate the impact of sevoflurane
      during long-term sedation of critically ill patients on 'weaning time',
      efficiency, and patient's safety compared to the standard intravenous sedation
      concept employing propofol. TRIAL REGISTRATION: EudraCT2007-006087-30;
      ISRCTN90609144.

PMID- 22883021
TI  - Comparison of the broth microdilution (BMD) method of the European Committee on
      Antimicrobial Susceptibility Testing and the Clinical Laboratory Standards
      Institute BMD method for non-Candida albicans and non-C. tropicalis bloodstream
      isolates from eleven tertiary hospitals in Sao Paulo state, Brazil.
AB  - We aim in this study to provide levels of susceptibility of 162 bloodstream
      isolates of non-Candida albicans and non-C. tropicalis species from a sentinel
      program conducted in 11 hospitals in Brazil. Additionally, we compared the broth
      microdilution (BMD) method of the European Committee of Susceptibility Testing
      (EUCAST) with Clinical Laboratory Standards Institute (CLSI) BMD method for
      fluconazole, itraconazole, voriconazole, and amphotericin B. The study included
      103 C. parapsilosis, 38 C. glabrata, 8 C. orthopsilosis, and 7 C. krusei
      isolates, and single isolates of Pichia anomala, C. famata, C. lusitaniae, C.
      kefyr, C. guilliermondii, and C. metapsilosis. Of note, we observed cross
      resistance between fluconazole and voriconazole for two isolates being one C.
      parapsilosis and one C. glabrata. Good essential agreement (EA) was observed
      between the EUCAST and the CLSI results for C. parapsilosis and for fluconazole,
      itraconazole, voriconazole, and amphotericin B, respectively: 98%, 99%, 98%, and
      97%. Otherwise, for C. glabrata, the EA for fluconazole was 84.2% and for
      voriconazole 89.4%. Because data from Brazil are scarce, our results contribute
      to the consolidation of the database of candidemia agents and monitoring of
      trends in the profile of drug resistance.

PMID- 22883022
TI  - Economic evaluation of health consequences of prenatal methylmercury exposure in
      France.
AB  - BACKGROUND: Evidence of a dose-response relationship between prenatal exposure to
      methylmercury (MeHg) and neurodevelopmental consequences in terms of IQ
      reduction, makes it possible to evaluate the economic consequences of MeHg
      exposures. OBJECTIVE: To perform an economic evaluation of annual national
      benefits of reduction of the prenatal MeHg exposure in France. METHODS: We used
      data on hair-Hg concentrations in French women of childbearing age (18-45 years)
      from a national sample of 126 women and from two studies conducted in coastal
      regions (n = 161and n = 503). A linear dose response function with a slope of
      0.465 IQ point reduction per MUg/g increase in hair-Hg concentration was used,
      along with a log transformation of the exposure scale, where a doubling of
      exposure was associated with a loss of 1.5 IQ points. The costs calculations
      utilized an updated estimate of ?2008 17,363 per IQ point decrement, with three
      hypothetical exposure cut-off points (hair-Hg of 0.58, 1.0, and 2.5 MUg/g).
      RESULTS: Because of higher exposure levels of women in coastal communities, the
      annual economic impacts based on these data were greater than those using the
      national data, i.e., ? 1.62 billion (national), and ? 3.02 billion and ? 2.51
      billion (regional), respectively, with the linear model, and ? 5.46 billion
      (national), and ? 9.13 billion and ? 8.17 billion (regional), with the log model,
      for exposures above 0.58 MUg/g. CONCLUSIONS: These results emphasize that efforts
      to reduce MeHg exposures would have high social benefits by preventing the
      serious and lifelong consequences of neurodevelopmental deficits in children.

PMID- 22883023
TI  - Arsenic exposure through drinking water increases the risk of liver and
      cardiovascular diseases in the population of West Bengal, India.
AB  - BACKGROUND: Arsenic is a natural drinking water contaminant affecting 26 million
      people in West Bengal, India. Chronic arsenic exposure causes cancer,
      cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims
      of the present study were to assess bioindicators of hepatocellular injury as
      indicated by the levels of liver enzymes, to determine the auto immune status, as
      indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA
      antibodies in their serum, and to predict cardiovascular risk in the arsenic
      exposed population. METHODS: Effect of chronic arsenic exposure on liver was
      determined by liver function tests. Autoimmune status was measured by measuring
      ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased
      cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. RESULTS: Our
      results indicated that serum levels of bilirubin, alanine transaminase, aspartate
      transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed
      population. Serum levels of IL6 and IL8 also increased in the arsenic exposed
      group. CONCLUSIONS: Chronic arsenic exposure causes liver injury, increases the
      serum levels of autoimmune markers and imparts increased cardiovascular risk.

PMID- 22883025
TI  - BAFF and BAFF-R levels are associated with risk of long-term kidney graft
      dysfunction and development of donor-specific antibodies.
AB  - There are lines of evidence that B cells may play a role in transplantation. B
      cell activating factor, BAFF, is a homotrimer that has been shown to play a role
      in B cell survival, maturation and activation. To date, little is known of the
      role of BAFF and its receptors in transplantation. We analyzed the level of BAFF
      mRNA and its soluble protein, as well as transcripts coding for its receptors,
      BAFF-R, TACI and BCMA, in the blood of 143 patients with stable kidney transplant
      function 5 years or more posttransplantation. Three endpoints were analyzed: the
      time to renal dysfunction, the time to appearance of anti-HLA antibodies and the
      time to development of donor-specific antibodies. We established threshold values
      for BAFF and BAFF-R and showed that (1) stable patients with high BAFF-R levels
      had a higher risk of developing graft dysfunction, (2) patients with lower levels
      of BAFF transcripts or a higher level of soluble BAFF had a significantly higher
      risk of developing donor-specific antibodies. These data suggest that BAFF
      constitutes a risk factor for renal graft dysfunction and development of donor
      specific antibodies. They also suggest that agents targeting BAFF-R interactions
      may offer new therapeutic opportunities in transplantation.

PMID- 22883024
TI  - Loss of compatibility might explain resistance of the Arabidopsis thaliana
      accession Te-0 to Golovinomyces cichoracearum.
AB  - BACKGROUND: The establishment of compatibility between plants and pathogens
      requires compliance with various conditions, such as recognition of the right
      host, suppression of defence mechanisms, and maintenance of an environment
      allowing pathogen reproduction. To date, most of the plant factors required to
      sustain compatibility remain unknown, with the few best characterized being those
      interfering with defence responses. A suitable system to study host compatibility
      factors is the interaction between Arabidopsis thaliana and the powdery mildew
      (PM) Golovinomyces cichoracearum. As an obligate biotrophic pathogen, this fungus
      must establish compatibility in order to perpetuate. In turn, A. thaliana
      displays natural variation for susceptibility to this invader, with some
      accessions showing full susceptibility (Col-0), and others monogenic dominant
      resistance (Kas-1). Interestingly, Te-0, among other accessions, displays
      recessive partial resistance to this PM. RESULTS: In this study, we characterized
      the interaction of G. cichoracearum with Te-0 plants to investigate the basis of
      this plant resistance. We found that Te-0's incompatibility was not associated
      with hyper-activation of host inducible defences. Te-0 plants allowed germination
      of conidia and development of functional haustoria, but could not support the
      formation of mature conidiophores. Using a suppressive subtractive hybridization
      technique, we identified plant genes showing differential expression between
      resistant Te-0 and susceptible Col-0 plants at the fungal pre-conidiation stage.
      CONCLUSIONS: Te-0 resistance is likely caused by loss of host compatibility and
      not by stimulation of inducible defences. Conidiophores formation is the main
      constraint for completion of fungal life cycle in Te-0 plants. The system here
      described allowed the identification of genes proposed as markers for
      susceptibility to this PM.

PMID- 22883027
TI  - Arylazolyl(azinyl)thioacetanilides. Part 10: design, synthesis and biological
      evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1
      inhibitors.
AB  - In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with
      novel structures, we have employed a scaffold hopping strategy to explore the
      chemically diversed space of bioactive compounds. The original
      arylazolylthioacetanilide platform was replaced with different
      imidazopyridinylthioacetanilide scaffolds to yield the optimal pharmacophore
      moieties in order to generate novel NNRTIs with desirable potency. Some of the
      new compounds proved able to inhibit HIV-1 replication in the low micromolar
      range. In particular, compound 5b16 displayed the most potent anti-HIV-1 activity
      (EC(50) = 0.21 +/- 0.06 MUM), inhibiting HIV-1 IIIB replication in MT-4 cells
      more effectively than dideoxycytidine (EC(50) = 1.4 +/- 0.1 MUM) and similarly
      with nevirapine (EC(50) = 0.20 +/- 0.10 MUM). Preliminary structure-activity
      relationship (SAR) of the newly synthesized congeners is discussed, and molecular
      modeling study is performed to rationalize the SAR conclusions.

PMID- 22883026
TI  - Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor
      receptor 2 (VEGFR2) inhibitors: 3. Evaluation of 5-amino-linked thiazolo[5,4
      d]pyrimidine and thiazolo[5,4-b]pyridine derivatives.
AB  - Our aim was to discover RAF/vascular endothelial growth factor receptor 2
      (VEGFR2) inhibitors that possess strong activity and sufficient oral absorption,
      and thus, we selected a 5-amino-linked thiazolo[5,4-d]pyrimidine derivative as
      the lead compound because of its potential kinase inhibitory activities and its
      desired solubility. The novel tertiary 1-cyano-1-methylethoxy substituent was
      designed to occupy the hydrophobic region of 'back pocket' of BRAF on the basis
      of the X-ray co-crystal structure data of BRAF. In addition, we found that N
      methylation of the amine linker could control the twisted molecular conformation
      leading to improved solubility. These approaches produced N-methyl thiazolo[5,4
      b]pyridine-5-amine derivative 5. To maximize the in vivo efficacy, we attempted
      salt formation of 5. Our result indicated that the besylate monohydrate salt form
      (5c) showed significant improvement of both solubility and oral absorption. Owing
      to the improved physicochemical properties, compound 5c demonstrated regressive
      antitumor efficacy in a HT-29 xenograft model.

PMID- 22883028
TI  - Analysis of the structural and mechanistic factors in antioxidants that preserve
      mitochondrial function and confer cytoprotection.
AB  - Selected pyridinol analogues of the experimental neuroprotective drug idebenone
      have been synthesized and evaluated as antioxidants capable of preserving
      mitochondrial function. The compounds, having a different redox core but the same
      side chain as idebenone, exhibited a range of potencies, reflecting differences
      in their structures. The results obtained provide guidance in the design of such
      analogues with improved properties. Analogues were identified that have
      significantly improved antioxidant activity compared with idebenone in cultured
      lymphocytes, and which exhibit lesser inhibition of the electron transport chain.

PMID- 22883029
TI  - The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium
      yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.
AB  - The alpha-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered
      thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was
      investigated for its inhibition with a large series of sulfonamides and a
      sulfamate, the classical inhibitors of these zinc enzymes. SspCA showed an
      inhibition profile with these compounds very similar to that of the predominant
      human cytosolic isoform hCA II, and not to that of the bacterial alpha-CA from
      Helicobacter pylori. Some clinically used drugs such as acetazolamide,
      methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide,
      topiramate, celecoxib and sulthiame were low nanomolar SspCA/hCA II inhibitors
      (KIs in the range of 4.5-12.3nM) whereas simple aromatic/heterocyclic
      sulfonamides were less effective, micromolar inhibitors. As this highly
      catalytically active and thermostable enzyme may show biotechnological
      applications, its inhibition studies may be relevant for designing on/off systems
      to control its activity.

PMID- 22883030
TI  - [The challenges for nutritional management in premature infants].

PMID- 22883031
TI  - [Present situation of neonatal subspecialty in the mainland of China: a survey
      based on 109 hospitals].
AB  - OBJECTIVE: To investigate the present situation of neonatal subspecialty in the
      mainland of China, and provide reference data for further development and
      standardization of neonatal discipline in China. METHODS: Data of neonatal
      subspecialty of 109 hospitals in the mainland of China acquired by questionnaire
      were collected and analyzed. RESULTS: Of the 109 hospitals that located in 22
      provinces, municipalities and autonomous regions, 68 (62.4%) had independent
      neonatology departments, and 41 (37.6%) had neonatal subspecialty groups
      affiliated to pediatric departments. The average number of neonatal beds was
      35.95 (range from 6 to 300, median 30) per unit, compared with a number of 45.21
      per unit in grade III-A general hospitals (range from 6 to 300, median 30). In
      all the 109 hospitals, the general beds to physicians ratio and beds to nurses
      ratio were 1:3.24 and 1:1.42, respectively. Each unit was in average equipped
      with 4.50 infant radiant warmers, 23.83 neonatal incubators, 3 normal frequency
      ventilators and 2.55 CPAP ventilators. All 22 clinical technologies, including
      ECMO, had been carried out, but only the new resuscitation technique has been
      carried out in each of these hospitals, and there were still eight technologies
      that were carried out in less than 50% hospitals. Totally 139 084 infants were
      treated in 109 hospitals in 2008, with the average number of 1276 patients per
      unit (range from 32 to 5500, median 1160). The average survival rate and
      mortality rate during hospitalization were 95.31% and 1.43%, respectively, while
      the survival rate of very low birth weight premature infants and extremely low
      birth weight premature infants were 82.43% and 41.30%, respectively. Transport
      service was provided in 62 (56.9%) hospitals, with the average transport number
      of 330 infants per hospital, accounting for 20.28% of the total admission.
      CONCLUSION: The survey shows that neonatal subspecialty in the mainland of China
      already has a considerable size, however, the development is not balanced. The
      system of classification of neonatal units and standards of ward construction
      suitable for China should be set up as soon as possible.

PMID- 22883032
TI  - [Diagnosis of patent vitellinc duct and patent urachus with ultrasound in an
      infant].

PMID- 22883033
TI  - [Clinical characteristics of bilirubin encephalopathy in Chinese newborn infants
      a national multicenter survey].
AB  - OBJECTIVE: Bilirubin encephalopathy continued to be reported worldwide. This
      multicenter study was conducted to explore the clinical characteristics,
      comorbidities and prognosis of bilirubin encephalopathy in China. METHODS: The
      survey was conducted in 33 level III hospitals. Clinical charts of infants with
      diagnosis of bilirubin encephalopathy or kernicterus at discharge were reviewed.
      The data were collected by a detaild questionnaire and analyzed. RESULTS: From
      January to December in 2009, 348 cases of bilirubin encephalopathy were reported
      from 28 hospitals. The mean birth weight was (3112.4 +/- 599.6) grams, mean
      gestational age was (38.3 +/- 2.3) weeks; 291 (83.6%) cases were term infants, 40
      (11.5%) cases were late-preterm infants, and 11 (3.2%) cases were early preterm
      infants. After admission, the highest bilirubin level was (478.1 +/- 175.8)
      umol/L. Of all the 348 cases, the age at admission was (7.3 +/- 5.4) days; 247
      (71.0%) cases were admitted before 7 days of age, 24 (6.9%) cases were admitted
      after 14 days of age. Most of the cases (86.2%) were complicated with other
      conditions, including bacterial infection (52.6%), ABO incompatibility (29.9%),
      and perinatal asphyxia (10.1%). A total of 131 infants (37.6%) underwent an
      exchange transfusion. Use of albumin, intravenous immunoglobulin was also common
      (68.7% and 44.0% respectively). A total of 52 cases were of minority ethnic
      groups, with significantly higher rate of G6PD deficiency than Han ethnicity
      cases. During the hospitalization and follow up, 36 infants died, and 125 infants
      (35.9%) were lost to follow up. CONCLUSIONS: Bilirubin encephalopathy is still
      not rare in China, the establishment of a population-based reporting system and
      prevention of kernicterus remain a high priority among public health
      institutions.

PMID- 22883034
TI  - [Multicenter study on the effects of human milk fortification in premature
      infants].
AB  - OBJECTIVE: To study the effects of human milk fortification on growth and safety
      in premature infants in China during hospital stay. METHODS: A prospective
      controlled study was conducted in 4 tertiary hospitals in Beijing and Shanghai,
      premature infants born from Nov. 2009 to Mar. 2011 were included according to
      certain enrollment criteria. Premature infants were divided into two groups:
      fortified human milk group, i.e., FHM group who were fed with human milk over 50
      percent during hospital stays, preterm formula was used for those whose mothers
      did not have enough milk, and preterm formula group as control who were fed fully
      with preterm formula. The enteral and parenteral nutritional intakes,
      complications and growth were compared between the two groups. RESULTS: Among the
      125 cases included, 62 were in the HMF group, and 63 were in the preterm formula
      group. Birth weight of HMF group (1429.1 +/- 209.0) g was lower than that of the
      preterm formula group (1514.0 +/- 210.5) g, there was no significant difference
      in gestational age, head circumference, length at birth, and correction
      gestational age at discharge, weight, head circumference and length at discharge,
      time for regaining birth weight, the mean daily protein, length of
      hospitalization between the two groups (P > 0.05). There was also no significant
      difference in the days for achieving total energy intake of 120 cal/(kg.d) and
      150 ml/(kg.d) through enteral feeding between the two groups. The velocity of
      gaining weight, head circumference, and length after regaining birth weight 0.7
      vs. 0.6 cm/W;1.1 vs. 0.9 cm/W were similar between the 2 groups. The biochemical
      parameters were similar at birth, but the serum urea nitrogen, prealbumin levels
      in FHM group were lower than those in the control group [(2.20 +/- 1.17) vs.
      (2.66 +/- 1.21) mmol/L (P = 0.036); (91.33 +/- 21.21) vs. (107.0 +/- 33.58) mg/L
      (P = 0.003)], while the calcium levels were higher than those of the control
      group [(2.48 +/- 0.21) vs. (2.39 +/- 0.15) mmol/L, P = 0.016]. Serum alkaline
      phosphatase and phosphor showed no significant difference [(2.01 +/- 0.36) vs.
      (2.02 +/- 0.42) mmol/L; (311.68 +/- 142) vs. (284.67 +/- 111) U/L]. Nosocomial
      infection in the FHM group was significantly lower than that in the control group
      [10 cases (16.1%) vs. 20 cases (31.7%), P = 0.021], there was no significant
      difference in incidence of feeding intolerance, necrotizing enterocolitis (NEC)
      between the two groups. The frequency and lasting time of feeding intolerance was
      obviously less in the FHM group than that in the control group. CONCLUSION:
      Premature infants fed with fortified human milk showed similar growth pattern to
      those fed with preterm formula during hospital stay. FHM may decrease the
      incidence of nosocomial infection and feeding intolerance.

PMID- 22883035
TI  - [Clinical study of myocardial damage induced by neonatal jaundice in normal birth
      weight term infants].
AB  - OBJECTIVE: To clarify whether neonatal jaundice may cause myocardial damage to
      term infants with normal birth weight (BW). METHODS: Totally 178 term neonates
      admitted during March, 2004 to December, 2010 with normal BW were enrolled.
      Infants with antenatal or neonatal asphyxia, temperature abnormality, septicemia,
      antenatal viral infection, congenital dysmorphia, congenital heart disease, 21
      trisomy, and polycythemia were excluded. There was no maternal complications
      during the pregnancy. Serum total bilirubin (TB), creatine kinase (CK), MB
      isoenzymes of creatine kinase (CK-MB), and cardiac troponin-I (cTnI) were
      measured. Patients with transcutaneous bilirubin level (TcB) >= 342 umol/L (20
      mg/dl) were in Group A (n = 32), and those with TcB below phototherapy level at
      matched time point were in Group B (n = 25). ECG, for correct Q-T intervals (QTc)
      and correct QT intervals dispersion (QTcd), and ECHO, for left ventricular
      ejection fraction (EF), the ratio of the peak velocity of early stage and
      advanced stage of diastolic phase at the mitral orifice (E/A), were applied to
      patients in Group A and B. SPSS 13.0 software was used for the data analysis. The
      coefficients of correlation among age in hours on admission (hr), TB, CK, CK-MB,
      CK-MB/CK, and cTnI were studied by multiple and partial correlation analysis.
      Data in Group A and B were compared by independent-samples Mann-Whitney U test
      (nonparametric method) or Student t-test. RESULTS: When the data were analyzed by
      multiple correlation, there were significant correlation between TB and cTnI, CK
      MB, respectively (r = 0.212, -0.161, respectively, all P < 0.05). But, when the
      data were analyzed by partial correlation, there was no correlation between TB
      and cTnI, CK-MB, respectively (r' = 0.112, -0.112, respectively, all P > 0.05),
      negative correlation between hr and TB, cTnI, respectively (r' = -0.490, P =
      0.000; r' = -0.162, P = 0.032). There was no significant difference in CK (Z = 
      1.384, P = 0.166), CK-MB (Z = -0.821, P = 0.412), cTnI (Z = -1.159, P = 0.246),
      QTc (t = 1.146, P = 0.257), QTcd (t = 1.342, P = 0.185), EF (t = 1.558, P =
      0.125), E/A (t = -0.640, P = 0.525) between group A and B. There was significant
      difference in CK-MB/CK (Z = -3.187, P = 0.001) between group A and B with a lower
      value in group A [0.075 (0.032 - 0.102)] comparing to that in group B [0.160
      (0.073 - 0.284)]. CONCLUSION: There is no sufficient evidence to support the
      hypothesis that neonatal jaundice may induce myocardial damage in normal birth
      weight term infants.

PMID- 22883036
TI  - [Clinical evaluation of the effects of morphine in mechanical ventilation of
      neonates].
AB  - OBJECTIVE: To evaluate the effects of morphine infusion analgesia on behavioural
      and neuroendocrine stress response and short term outcome in ventilated neonates.
      METHODS: A randomized, double-blind clinical trial was conducted between August
      2010 and April 2011 at the neonatal intensive care unit of Nanjing Children's
      Hospital Affiliated to Nanjing Medical University. A total of 46 ventilated
      preterm infants (>= 32 weeks) and term infants were divided into 2 groups at
      random. Twenty-two infants in test group received a loading dose (100 ug/kg) of
      morphine (> 1 h) followed by a continuous infusion [10 ug/(kg.h)] for (70.05 +/-
      29.05) h, and 24 infants in control group received 5% glucose with the same
      infusion rate. (1) The ventilatory parameters [respiratory rate (R), frequence
      (f), peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP),
      fraction of inspired oxygen (FiO2)], mean blood pressure (MBP) and heart rate
      (HR) before treatment, at 30 min, 2 h, 6 h, 12 h, 24 h, 48 h after treatment
      between two groups were compared. (2) Pain was measured by two assessment tools
      [neonatal pain, agitation and sedation scale (N-PASS) and COMFORT scale] at the
      same periods. (3) The ventilation duration, the time from withdrawal to
      extubation, the total oxygen-inhaled time, the side effects and the clinical
      outcomes [e.g., pulmonary hemorrhage, air leak, patent ductus arteriosus (PDA),
      necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH)] between two
      groups were compared. RESULTS: (1) There were no significant differences in the
      different ventilatory parameters before and after treatment between two groups at
      different periods (P > 0.05). There was no significant difference in the average
      blood pressure of two groups at different periods, but the heart rate reduced at
      24 - 48 h after treatment in test group with significant difference as compared
      to control group (t = -2.152 and -2.513, P < 0.05). (2) The N-PASS score and
      COMFORT score in test group were lower than that in control group at different
      time points 2 h after treatment (P < 0.05), especially 12 h after treatment (P <
      0.01). (3) There were no significant differences in the ventilation duration, the
      time from withdrawal to extubation and the total oxygen time between two groups,
      and also in side effects, the incidence of IVH, white matter damage and the
      clinical outcomes. CONCLUSION: Continuous infusion of morphine could relieve pain
      in ventilated neonates, reduce the stress response and promote the human-machine
      coordination, but the medication did not show any effects on neurobehavioral
      development and short term outcome.

PMID- 22883037
TI  - [Influence of human mesenchymal stem cells on hyperoxia-exposed newborn rats by
      RAGE-NF-kappaB signaling in lung].
AB  - OBJECTIVE: To investigate the influence of high oxygen exposure on signaling
      pathway of the receptor for advanced glycation end products (RAGE)-NF-kappaB of
      lung in newborn rats and the mechanisms of protecting lung injury for human
      mesenchymal stem cells (hMSC). METHODS: Twenty-four newborn Sprague-Dawley rats
      from three litters were randomly divided into three groups, as hyperoxia exposed
      + hMSC group (group A), hyperoxia exposed group (group B), and air-exposed group
      (group C). The rats from the group A and B were placed in a sealed Plexiglas
      chamber with a minimal in-and outflow, providing six to seven exchanges per hour
      of the chamber volume and maintaining O(2) levels above 95%, while rats in the
      group C only exposed to air simultaneously. Seven days later, rats in the group A
      were injected intravenously with hMSC (5*10(4)) after hyperoxia exposure, but
      rats in group B and C received subcutaneous injection with PBS alone at the same
      time point. Then all the rats were exposed to air, and were sacrificed three days
      later. Immunohistochemistry was used to evaluate the expression of RAGE in lung
      tissue. The levels of TNF-alpha and sRAGE in bronchoalveolar lavage fluid (BALF)
      and in serum were detected by ELASA, RAGE mRNA and NF-kappaB mRNA in tissue
      homogenates were detected by RT-PCR, RAGE and NF-kappaB by Western blotting; also
      the value of lung damage score were calculated with histology under light
      microscope. RESULTS: There were significant differences among three groups in the
      fields of lung damage score (F = 51.59, P = 0.000), mRNA and protein of RAGE (F =
      37.21, P = 0.000; F = 15.88, P = 0.000) and NF-kappaB (F = 5.695, P = 0.011; F =
      4.223, P = 0.0288) in lung tissue homogenates, and the level of TNF-alpha (F =
      38.29, P = 0.000) in BALF, all these parameters in group A and group B were
      higher than that in group C. While sRAGE in BALF in group A and group B were less
      than that in group C (F = 4.804, P = 0.0191). There were also significant
      differences between group A and group B in these parameters (P < 0.05). There
      were also no significant differences neither in TNF-alpha nor in sRAGE in serum
      among three groups. CONCLUSIONS: hMSC protects hyperoxia-induced lung injury via
      downregulating the signaling pathway of RAGE-NF-kappaB.

PMID- 22883038
TI  - [Effects of propofol on expression of hippocampal survivin and Caspase-3 in
      newborn rats].
AB  - OBJECTIVE: Intravenous anesthetics, such as propofol, are widely used in general
      anesthesia. Neurodegeneration and neurocognitive impairment after exposure to
      propofol in neonatal rats have raised concerns regarding the safety of pediatric
      anesthesia. We examined the effects of neonatal propofol exposure on brain cell
      viability, as well as expression of hippocampal survivin and Caspase-3 mRNA and
      protein. METHODS: One hundred male Sprague-Dawley rats aged 7 d that were weighed
      10-15 g were randomly divided into 4 groups (n = 25 each group). Group A: the
      rats were injected with no drugs. Group B: the rats were intraperitoneally
      injected with 50 mg/kg propofol. Group C: the rats were first intraperitoneally
      injected with 50 mg/kg propofol and another 50 mg/kg propofol was used when the
      dynamic response of rats appeared again. Group D: the rats were first
      intraperitoneally injected with 50 mg/kg propofol and another 50 mg/kg propofol
      was used three times once the dynamic response of rats appeared. To study the
      effects of propofol exposure on respiratory and metabolic function, arterial
      blood was aspirated from the left ventricle of neonatal rats 2 h after
      discontinuation of propofol. pH, PaO(2), PaCO(2), HCO(3)(-), BE and SaO(2) were
      detected by blood gas analyzer. Moreover, to examine the effects of propofol
      exposure on short-term cellular viability, the ultrastructure of neurons was
      observed by transmission electron microscope and Fluoro-Jade B (FJB) staining was
      performed to examine neuronal degeneration in hippocampal CA1 region of neonatal
      rats. Survivin and Caspase-3 mRNA and protein expression in hippocampus were
      detected by semi-quantitative reverse transcription polymerase chain reaction (RT
      PCR) and Western blotting 2 h after discontinuation of propofol. RESULTS: The
      time of anesthesia maintaince in newborn rats was the longest in Group D and the
      time of anesthesia maintaince in Group C was longer than that in Group B. Two
      hours after discontinuation of propofol, pH, PaO(2), PaCO(2), HCO(3)(-), BE and
      SaO(2) of arterial blood in rats were not significantly different among groups A,
      B, C and D (P > 0.05). The structure of hippocampal neurons was normal in Group A
      and Group B while 100 mg/kg propofol resulted in nuclear blebbing and 200 mg/kg
      propofol led to nuclear fragmentation, chromatin condensation and apoptotic
      bodies. Cellular degeneration, as measured by Fluoro-Jade B staining,
      significantly increased in hippocampal CA1 region in the anesthesia groups
      compared with littermates in the no anesthesia group. FJB-positive stained
      degenerative neurons in groups B, C and D were (2.5 +/- 1.3), (7.1 +/- 2.3) and
      (9.4 +/- 2.6), which were different from that in Group A (0.6 +/- 0.3) (P <
      0.05). Moreover, the number of FJB-positive neurons was the highest in Group D,
      that in Group C was more than that in Group B. At the same time point, apoptosis
      was measured by expression of Caspase-3 and Survivin mRNA and protein in
      hippocampus of rats. Caspase-3 mRNA in groups A, B and C was (0.78 +/- 0.12),
      (0.84 +/- 0.17) and (0.89 +/- 0.19), while Caspase-3 protein in groups A, B and C
      was (0.22 +/- 0.05), (0.26 +/- 0.07) and (0.21 +/- 0.06). Survivin mRNA in groups
      A, B and C was (0.56 +/- 0.12), (0.58 +/- 0.15) and (0.53 +/- 0.16), while
      Survivin protein in these 3 groups was (0.24 +/- 0.07), (0.21 +/- 0.05) and (0.23
      +/- 0.06). Compared with that in Group A, Caspase-3 and Survivin mRNA and protein
      were not significantly different among Group B and Group C (P > 0.05). However,
      Caspase-3 mRNA and protein in Group D were (1.21 +/- 0.14) and (0.42 +/- 0.12),
      which were higher than that in the other 3 groups (P < 0.05). Survivin mRNA and
      protein in Group D were lower than that in the other 3 groups (P < 0.05).
      CONCLUSIONS: A high dose of propofol exposure may destroy the structure of
      neurons, induce neurodegeneration, increase Caspase-3 activity and inhibit
      survivin expression in hippocampus of newborn rats in vivo.

PMID- 22883039
TI  - [Premature rupture of the membrane and cerebral injury of premature infants].

PMID- 22883040
TI  - [Recent advances in diagnosis of mixed phenotype acute leukemia].

PMID- 22883041
TI  - [Clinical and genetic study of twelve Chinese patients with Alexander disease].
AB  - OBJECTIVE: To delineate the phenotype and genotype characteristics in 12 Chinese
      children with Alexander disease (AD), which is helpful for the molecular
      diagnosis and genetic counseling in China. METHODS: Clinical diagnosis of AD was
      based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients
      were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA
      sequencing. RESULTS: The 12 cases of AD were clinically diagnosed. Age of first
      visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints:
      developmental delay in 3, recurrent seizures in 7, unable to walk after falling
      in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age
      matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according
      to Gross motor functional classification system (GMFCS) was performed, with
      GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in
      8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67
      years, their motor and cognitive function remained stable. Episodic aggravations
      provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous
      missense mutations of GFAP were detected in 12 patients. All mutations were de
      novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot
      mutations, which was consistent with previous reports. Mutations were located in
      exon 1 in 8 cases. CONCLUSIONS: The phenotype in these patients is characterized
      by slower progression compared with reports from other population and high
      incidence of seizures. And episodic aggravations provoked by fever or falling
      were more common. The genotype characteristics are consistent with previous
      reports. The results of this research expanded the number of patients with
      Alexander disease found to have GFAP coding mutations in China.

PMID- 22883042
TI  - [Relationship between B/C genotype of hepatitis B virus and hepatitis B virus
      related-nephritis in children].
AB  - OBJECTIVE: To investigate the relationship between genotype of hepatitis B virus
      and hepatitis B virus related-glomerular nephritis in (HBV-GN) children. METHOD:
      Totally 176 HBV-DNA positive children with chronic hepatitis B were randomly
      collected. Among the 176 patients, 92 were HBV carriers, 84 were cases with
      chronic hepatitis. The genotypes of their serum HBV, liver function, and HBV-DNA
      load were detected. When children showed nephrotic syndrome, renal biopsy was
      performed. RESULT: Of the serum samples of 176 cases, 85 (48.3%) were genotype C,
      72 (40.9%) were genotype B, 13 (7.4%) were genotype B/C, and 6 (3.4%) were non
      B/C genotype which were excluded. Among the analyzed 157 cases, the ratio of HBV
      GN in the HBeAg positive group (78.3%) was significantly higher than that in the
      negative group (21.7%) (chi(2) = 18.301, P < 0.001). And, the ratio of HBV-GN in
      the genotype C group (73.9%) was significantly higher than that in the genotype B
      group (26.1%) (P < 0.039). The ratio of hematuria or proteinuria in the genotype
      C group (20%, 18.8%) was significantly higher than that in the genotype B group
      (8.3%, 5.6%) (P < 0.039; P value = 0.013); and the alteration of ALT or C3 in the
      genotype C group (10.2%, 15.3%) was more frequent than those in the genotype B
      group (2.8%, 2.8%) (P = 0.005; P = 0.008). There were no significant differences
      in kidney dysfunction or hepatomegaly. Further, the ratio of HBV-GN was more
      significantly frequent in HBV-DNA highly loading group (79.2%) than which in HBV
      DNA lowly loading group (20.8%) (P = 0.000). Finally, in HBV-GN group, genotype C
      cases (88.2%) more frequently had high HBV-DNA load condition than genotype B
      cases (11.8%) (P = 0.021). CONCLUSION: Children with HBV infection in Gansu
      province showed mainly genotypes C or B, while genotype C seemingly predominant.
      Patients with genotype C more frequently showed proteinuria or hematuria. The
      high HBV-DNA load may be related with HBV-GN. It is a potential reason in the
      mechanism of HBV-GN that patients with genotype C had more possibility to have
      HBV-DNA high load. Analysis of HBV genotype for HBV patients maybe helpful in
      diagnosis and treatment.

PMID- 22883043
TI  - [Clinical features of chronic granulomatous disease].
AB  - OBJECTIVE: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency
      of phagocytic oxidative bursts leading to recurrent severe bacterial and fungal
      infections as well as granuloma formation. There were few reports on the clinical
      characteristics of this disease in China. The purpose of this study was to
      evaluate the clinical features of 48 Chinese cases with CGD which were confirmed
      by clinical features, dihydrorhodamine (DHR) assay and gene mutation analysis.
      METHOD: The study cohort was the population of CGD patients diagnosed in
      Children's Hospital of Fudan University from January, 2004, to June, 2011. Cases
      included in our analysis were restricted to those who had complete data of the
      clinical symptoms and laboratory tests. The patients were followed up by
      outpatient visiting and telephone call regularly for 0.5 to 6 years. The history
      and data of physical examination and treatment of 48 cases were collected and
      reviewed. RESULT: All the patients were diagnosed by DHR analysis. The age of
      onset of all the 48 patients were less than 6 months, including 43 male and 5
      female. The mean age at diagnosis was 2.42 years; 12 patients were infants under
      six months, 10 were between 6 and 12 months, 9 were between 1 and 2 years, 5
      patients were between 2 and 3 years, 4 were between 4 and 5 years, and 8 were
      between 6 and 10 years. Recurrent respiratory infection (44/48) and chronic
      diarrhea (31/48) were the common symptoms in all the patients, and then skin
      lesion (22/48), including marked reaction at BCG infected site, pustular eruption
      and infected skin ulcer and urinary tract infection (3/48) were also general
      symptoms in our study. In addition, lymphadenectasis occurred in 31 cases and 23
      of them were considered to be associated with BCG vaccination. The pathogens
      caused the infection were mycobacteria (52.08%), fungi (43.75%) and pyogenic
      bacteria. Thirty-seven patients had mutations in CYBB/CYBA/NCF1/NCF2 genes.
      Recombinant human interferon-gamma (rhIFN-gamma) plus sulfamethoxazole were used
      for the prevention and treatment of infection, the frequency and severity of the
      disease could be reduced. CONCLUSION: The age at onset and diagnosis of the
      present group of CGD was younger. Clinical symptoms were associated with
      recurrent mycobacterial, fungal and pyogenic bacterial infection, which involved
      respiratory tract, alimentary tract, skin and lymph node. rhIFN-gamma partially
      improved the prognosis of CGD.

PMID- 22883044
TI  - [Screening for cytotoxic defects with flow cytometric detection of CD107alpha on
      natural killer cells and cytotoxic lymphocyte cells].
AB  - OBJECTIVE: To establish a novel flow cytometry-based assay for measuring the
      expression of lysosomal-associated membrane protein 1 (LAMP-1, CD107alpha) on the
      cell surface of natural killer (NK) cells and cytotoxic T lymphocyte (CTL) and
      evaluate the screening value of this assay for cytotoxic defects-related diseases
      such as familial hemophagocytic lymphopro-liferative (FHL) syndrome. METHOD:
      Three suspected Chediak-Higashi Syndrome (CHS) patients, three suspected FHL
      patients and 10 healthy children were enrolled in the study from October 2010 to
      June 2011. Their PBMCs were separated and activated overnight with IL-2. After
      the granule release of NK cells activated by phytohemagglutinin (PHA) and CD8+T
      cells by anti-CD3, the CD107alpha expression were analyzed by flow cytometry. The
      peripheral blood DNA and RNA of the patients were extracted to analyze the
      pathogenic genes via DNA-PCR/RT-PCR and direct sequencing. RESULT: The CD107alpha
      expression on CTL in the ten healthy children significantly increased after
      activation by anti-CD3 [(0.18 +/- 0.07)% vs. (4.47 +/- 2.36)%, P < 0.05] and NK
      cells after activation by PHA [(0.27 +/- 0.07)% vs. (5.80 +/- 2.83)%, P < 0.05].
      The frequency of CD107alpha-expression NK cells in three suspected CHS after
      activation was significantly elevated when compared with the healthy control
      [0.5%, 0.6% vs. (5.80 +/- 2.83)%] except patient 2. After the anti-CD3
      activation, the frequency of CD107alpha expression on CTL cells also showed no
      significant difference [0.3%, 0.9%, 0.2% vs. (4.47 +/- 2.36)%] in three patients.
      All of their mean fluorescence intensity (MFI) showed the same trend. Patient 1
      and 3 were identified to have LYST mutations (Patient 1: c.5411-5414 del TTTC,
      L1741fsX1758 and c.7975 C > T, R2596X; Patient 3: c.4863G > A, R1563H and c.5392
      5393delAA, E1739fsX1756). There was no mutation identified in the LYST gene for
      patient 2. CD107alpha expression of NK cells and CTL in the suspected FHL
      patients and in mirror of these findings, no underlying gene variation of PRF,
      MUNC13-4 and STX11 were identified. CONCLUSION: We developed a method to
      quantitatively assess cytotoxicity of the NK cells and CTL by measuring the
      expression of CD107alpha on the cell membrane, which appeared to be an effective
      and rapid screening test for cytotoxic defects-related diseases such as FHL and
      other HLH secondary to primary immunodeficiency.

PMID- 22883045
TI  - [Perinatal diagnosis of pulmonary sequestration in a case].

PMID- 22883046
TI  - [Juvenile dermatomyositis presenting with anasarca: case report and literature
      review].

PMID- 22883047
TI  - [Report of a child with transient hyperphosphatasemia of infancy and early
      childhood].

PMID- 22883048
TI  - [Harrison groove is not the clinical sign of rickets of vitamin D deficiency].

PMID- 22883049
TI  - [Summary of the 3(rd) National Conference of Pediatric Syncope].

PMID- 22883050
TI  - Improving retrospective characterization of the food environment for a large
      region in the United States during a historic time period.
AB  - Access to healthy foods has received increasing attention due to growing
      prevalence of obesity and diet-related health conditions yet there are major
      obstacles in characterizing the local food environment. This study developed a
      method to retrospectively characterize supermarkets for a single historic year,
      2005, in 19 counties in 6 states in the USA using a supermarket chain-name list
      and two business databases. Data preparation, merging, overlaps, added-value
      amongst various approaches and differences by census tract area-level socio
      demographic characteristics are described. Agreement between two food store
      databases was modest: 63%. Only 55% of the final list of supermarkets were
      identified by a single business database and selection criteria that included
      industry classification codes and sales revenue >=$2 million. The added-value of
      using a supermarket chain-name list and second business database was
      identification of an additional 14% and 30% of supermarkets, respectively. These
      methods are particularly useful to retrospectively characterize access to
      supermarkets during a historic period and when field observations are not
      feasible and business databases are used.

PMID- 22883051
TI  - Insights into the structure and pharmacology of the human trace amine-associated
      receptor 1 (hTAAR1): homology modelling and docking studies.
AB  - Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that
      belongs to the family of TAAR receptors and responds to a class of compounds
      called trace amines, such as beta-phenylethylamine (beta-PEA) and 3
      iodothyronamine (T(1)AM). The receptor is known to have a very rich pharmacology
      and could be also activated by other classes of compounds, including adrenergic
      and serotonergic ligands. It is expected that targeting TAAR1 could provide a
      novel pharmacological approach to correct monoaminergic dysfunctions found in
      several brain disorders, such as schizophrenia, depression, attention deficit
      hyperactivity disorder and Parkinson's disease. Only recently, the first
      selective TAAR1 agonist RO5166017 has been identified. To explore the molecular
      mechanisms of protein-agonist interaction and speed up the identification of new
      chemical entities acting on this biomolecular target, we derived a homology model
      for the hTAAR1. The putative protein-binding site has been explored by comparing
      the hTAAR1 model with the beta(2)-adrenoreceptor binding site, available by X-ray
      crystallization studies, and with the homology modelled 5HT(1A) receptor. The
      obtained results, in tandem with docking studies performed with RO5166017, beta
      PEA and T(1)AM, provided an opportunity to reasonably identify the hTAAR1 key
      residues involved in ligand recognition and thus define important starting points
      to design new agonists.

PMID- 22883053
TI  - Metabolic syndrome increases the risk of aggressive prostate cancer detection.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Metabolic syndrome can
      identify patients at high risk of cardiovascular disease. The prevalence of
      metabolic syndrome is increasing worldwide and is associated with increased age,
      obesity and hypogonadism. The association between metabolic syndrome and prostate
      cancer development has not been studied comprehensively, and published studies
      report divergent results. This study indicates that tumours detected in men with
      metabolic syndrome are more aggressive than those detected in men without this
      condition. OBJECTIVE: To further examine the association between metabolic
      syndrome (MS), prostate cancer (PC) detection risk and tumour aggressiveness.
      PATIENTS AND METHODS: From 2006 to 2010, 2408 men not receiving 5alpha-reductase
      inhibitors were scheduled for prostatic biopsy due to PSA above 4 ng/mL and/or
      abnormal digital rectal examination. MS was evaluated according to the National
      Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment
      of High Blood Cholesterol in Adults, Adult Treatment Panel III definition. Tumour
      aggressiveness was evaluated through biopsy Gleason score, clinical stage and
      risk of biochemical recurrence after primary treatment. RESULTS: The rates of PC
      detection were 34.5% and 36.4% respectively in men with and without MS, P =
      0.185. High grade PC rates (Gleason score 8-10) were 35.9% and 23.9%
      respectively, P < 0.001. The advanced disease rates (cT3-4 N0-1 M0-1) were 17%
      and 12.7% respectively, P = 0.841. The high risk PC rates (cT2c-4 or Gleason
      score 8-10 or PSA > 20) were 38.5% and 33.0% respectively, P = 0.581.
      Multivariate analysis confirmed that MS was not associated with the risk of PC
      detection but it was associated with an increased risk of high grade tumours
      (odds ratio 1.75, 95% CI 1.26-2.41), P < 0.001. CONCLUSION: MS seems not be
      associated with an increased risk of PC detection but it is associated with an
      increased risk of more aggressive tumours.

PMID- 22883052
TI  - Acute lung injury and the acute respiratory distress syndrome in the injured
      patient.
AB  - Acute lung injury and acute respiratory distress syndrome are clinical entities
      of multi-factorial origin frequently seen in traumatically injured patients
      requiring intensive care. We performed an unsystematic search using PubMed and
      the Cochrane Database of Systematic Reviews up to January 2012. The purpose of
      this article is to review recent evidence for the pathophysiology and the
      management of acute lung injury/acute respiratory distress syndrome in the
      critically injured patient. Lung protective ventilation remains the most
      beneficial therapy. Future trials should compare intervention groups to controls
      receiving lung protective ventilation, and focus on relevant outcome measures
      such as duration of mechanical ventilation, length of intensive care unit stay,
      and mortality.

PMID- 22883054
TI  - Mechanisms of intrinsic and acquired resistance to kinase-targeted therapies.
AB  - Cancer drugs that target pivotal signaling molecules required for malignant cell
      survival and growth have demonstrated striking antitumor activities in
      appropriately selected patient populations. Unfortunately, however, therapeutic
      responses are often of limited duration, typically 6-12 months, because of
      emergence of drug-resistant subclones of tumor cells. In this review, we
      highlight several of the mechanisms of emergent resistance to several kinase
      targeted small molecule therapies used in melanoma, non-small cell lung cancer
      (NSCLC) and other solid tumors as illustrative examples. We discuss the
      implications of these findings for the development of new treatment strategies to
      delay or prevent the onset of drug resistance.

PMID- 22883055
TI  - [Obstructive sleep apnea syndrome and multiple systems consequences].

PMID- 22883056
TI  - [Diagnosis and treatment of obstructive sleep apnea hypopnea syndrome].

PMID- 22883057
TI  - [Diagnosis and treatment of central sleep apnea].

PMID- 22883058
TI  - [Proper recognition and understanding of complex sleep apnea].

PMID- 22883059
TI  - [Levels of blood pressure and blood glucose in elderly patients with hypertension
      and diabetes: association with carotid atherosclerosis].
AB  - OBJECTIVE: To explore the association between blood pressure and blood glucose
      levels and carotid atherosclerosis in elderly patients with essential
      hypertension and type 2 diabetes mellitus (T2DM). METHODS: A total of 670
      patients aged 60 years or over with hypertension and T2DM were recruited and
      categorized by their systolic blood pressure (SBP): tight control, < 130 mm Hg,
      usual control, 130 - 139 mm Hg, or uncontrolled, >= 140 mm Hg; and by their HbA1c
      level: tight control < 6.5%, usual control 6.5% - 7.5%, or uncontrolled, >= 7.5%
      respectively. Carotid ultrasonography was performed in all subjects for the
      evaluations of intima-media thickness (IMT) and plaque. RESULTS: Multiple linear
      regression analyses revealed that IMT was positively correlated with SBP (beta =
      0.215, P = 0.002) and HbA1c (beta = 0.149, P = 0.031), whereas IMT was negatively
      correlated with high-density lipoprotein cholesterol (beta = -0.196, P = 0.002).
      According to the multivariate logistic regression analysis, SBP >= 140 mm Hg (OR
      = 1.473, 95%CI 1.044 - 2.078 P = 0.027), HbA1c >= 7.5% (OR = 1.445, 95%CI 1.031 -
      2.027, P = 0.033) and total cholesterol (OR = 1.014, 95%CI 1.004 - 1.024, P =
      0.019) were significant risk factors for carotid artery atherosclerotic plaques
      whereas high-density lipoprotein cholesterol (OR = 0.895, 95%CI 0.805 - 0.994, P
      = 0.012) was a protective factor for carotid artery atherosclerotic plaques in
      elderly patients with hypertension and T2DM. CONCLUSION: There is a significant
      correlation between the levels of blood pressure, blood glucose and carotid
      atherosclerosis in elderly patients.

PMID- 22883060
TI  - [Expression of lymphokines in CD8(+)HLA-DR(+) T lymphocytes of patients with
      severe aplastic anemia].
AB  - OBJECTIVE: To examine the expression of lymphokines damaging hematopoietic cells
      by CD8(+)HLA-DR(+) effector T cells in peripheral blood (PB) of the patients with
      severe aplastic anemia (SAA) and explore further the heterogeneous
      immunopathogenesis of SAA. METHODS: The CD8(+)HLA-DR(+) cells were sorted by
      immunomagnetic separation from the PB of 24 untreated SAA patients and 23 normal
      controls. The mRNA expressions of perforin, granzyme B, FasL and tumor necrosis
      factor beta (TNF-beta) of sorted cells were analyzed by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The mRNA levels of perforin,
      granzyme B of CD8(+)HLA-DR(+)T cells in untreated group were higher than those of
      the controls (0.66 +/- 0.25, 0.56 +/- 0.26 vs 0.53 +/- 0.14, 0.40 +/- 0.13, P =
      0.042, 0.012). The mRNA level of FasL in CD8(+)HLA-DR(+) T cells of untreated SAA
      patients was higher than that of the controls (0.77 +/- 0.24 vs 0.61 +/- 0.16, P
      = 0.011). The mRNA of TNF-beta in CD8(+)HLA-DR(+) T cells of untreated SAA
      patients was also higher than that of the controls (0.58 +/- 0.16 vs 0.46 +/-
      0.15, P = 0.011). CONCLUSIONS: CD8(+)HLA-DR(+) T cells may damage hematopoiesis
      through the actions of perforin, granzyme B, TNF-beta and FasL. And it thus
      contributes to the immunopathogenesis of SAA.

PMID- 22883061
TI  - [Correlations of genetic polymorphisms of tumor necrosis factor-related apoptosis
      inducing ligand gene and its plasma phenotype with ulcerative colitis].
AB  - OBJECTIVE: To explore the correlations of genetic polymorphisms in tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) gene and the plasma levels of
      soluble TRAIL (sTRAIL) with ulcerative colitis (UC). METHODS: From May 2004 to
      April 2011, a total of 393 UC patients were recruited from Second and First
      Affiliated Hospitals of Wenzhou Medical College and Second Renmin Hospital of
      Wenzhou City. During the same period, a total of 1292 healthy controls were
      recruited from Physical Examination Center at Second Affiliated Hospital of
      Wenzhou Medical College. After PCR amplification, the genetic polymorphisms in
      TRAIL (G1525A, G1588A, C1595T) genes were examined by direct sequencing, and the
      haplotype analysis were also performed in all study subjects. Furthermore, the
      plasma levels of sTRAIL were determined by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The frequencies of variant genotypes in TRAIL (G1525A, G1588A,
      C1595T) genes were significantly lower in the UC patients than those in the
      controls (all P < 0.01). Both of variant allele frequencies in TRAIL G1525A and
      G1588A were significantly decreased in UC patients (40.08% (315/786) vs 54.95%
      (1420/2584), 49.49% (389/786) vs 55.53% (1435/2584), both P < 0.01). However, the
      variant allele frequency in TRAIL C1595T gene was not significantly lower in the
      UC patients (P = 0.133). According to disease severity, the UC patients were
      divided into mild, intermediate and severe groups. The frequencies of variant
      allele (T) and genotype (CT + TT) in TRAIL C1595T gene were also significantly
      higher in the patients with severe UC than those in others (63.50% (127/200) vs
      49.15% (288/586), 77.00% (77/100) vs 61.43% (180/293), both P < 0.01). In
      haplotype analysis, the frequency of GAT haplotype was significantly higher in
      the UC patients than that in the controls. However, the frequency of AAT
      haplotype was significantly lower in the UC patients (both P < 0.01).
      Furthermore, the plasma levels of sTRAIL were significantly higher in the UC
      patients than those in the controls ((1.05 +/- 0.48) vs (0.96 +/- 0.90) ng/L, P <
      0.01). CONCLUSION: The genetic polymorphisms of TRAIL (G1525A, G1588A, C1595T)
      and the plasma levels of sTRAIL are correlated with UC in Chinese patients.

PMID- 22883062
TI  - [Differential gene expression profiles of gastric cancer].
AB  - OBJECTIVE: To explore the different gene expressions of normal versus tumor
      tissues of gastric cancer at molecular levels. METHODS: Gene chip technology was
      used to determine the differentially expressed genes between gastric cancer (n =
      12) and normal tissues (n = 12) from December 2009 to June 2010 of Xinhua
      Hospital of Shanghai Jiaotong University School of Medicine. And reverse
      transcriptase (RT)-PCR was performed to validate the results of gene chip
      analysis. RESULTS: Sixty-nine up-regulated genes and 80 down-regulated genes were
      identified by significance analysis of microarrays (SAM). And these genes were
      correlated with cell adhesion, angiogenesis, cell proliferation and apoptosis, et
      al. They were also closely correlated with the signaling pathways of Wnt (1/151,
      0.66%) and vascular endothelial growth factor (VEGF) (2/76, 2.63%). The
      differential expressions of ATP4A, CLDN10, OLFM4, SAA1 and PROK2 were confirmed
      by RT-PCR (0.94 +/- 0.19 vs 4.33 +/- 0.39, 1.00 +/- 0.14 vs 3.04 +/- 0.26, 5.37
      +/- 0.30 vs 1.02 +/- 0.14, 4.37 +/- 0.30 vs 0.95 +/- 0.29, 2.62 +/- 0.54 vs 1.35
      +/- 0.35, all P < 0.05). CONCLUSION: The classifier genes identified in this
      study may be closely correlated with the carcinogenesis of gastric cancer.

PMID- 22883063
TI  - [Value of CD8(+) T lymphocyte subgroups for the predication of pulmonary invasive
      fungal infections in immunocompromised critically ill patients].
AB  - OBJECTIVE: To assess the predictive ability of CD8(+) T-cell counts and the
      expressions of CD28, CD38, HLA-DR on CD8(+) T cells in immunocompromised
      critically ill (ICCI) patients with pulmonary invasive fungal infections (PIFI).
      METHODS: The evolution of CD8(+) T-lymphocyte subgroups (CD8(+), CD8(+)CD28(+),
      CD8(+)CD38(+), CD8(+)HLA-DR(+)) were measured in the peripheral blood of 80 ICCI
      patients with pulmonary infection on day 1 (D1), 3 (D3) and 7 (D7) of intensive
      care unit (ICU) admission by quantitative flow cytometry. Forty immunocompetent,
      uninfected critically ill patients were analyzed as control subjects at the time
      of admission. Immunocompromised risk factors and PIFI was diagnosed according to
      European Organization for Research and Treatment of Cancer-Mycoses Study Group
      (EORTC-MSG) 2008 definitions. RESULTS: PIFI were diagnosed in 71.3% of the ICCI
      patients (57/80) and included 22 molds infections, 22 Candida infections and 13
      mixed infections. Among the 80 ICCI patients, CD8(+), CD8(+)CD28(+), and
      CD8(+)CD38(+) T-cell counts were significantly lower (P < 0.01) and CD8(+)HLA
      DR(+) T-cell counts were significantly higher (P < 0.01) than in the control
      subjects during the monitoring period, while CD8(+), CD8(+)CD28(+), and
      CD8(+)CD38(+) T cells demonstrated an additional significant decrease in PIFI
      patients compared with non-PIFI patients (P < 0.01). Receiver operating
      characteristic (ROC) analysis for discrimination of the 28-day mortality revealed
      area under the curve (AUC) values of 0.83, 0.84 and 0.87 for the CD8(+)CD28(+) T
      cell counts (D1, D3 and D7, respectively). Cutoff values of D1 < 64 cells/mm(3),
      D3 < 75 cells/mm(3), and D7 < 88 cells/mm(3) had sensitivities of 0.73 (95%CI:
      0.61 - 0.85), 0.74 (95%CI: 0.62 - 0.85), and 0.71 (95%CI: 0.58 - 0.84),
      specificities of 0.90 (95%CI: 0.77 - 1.00), 0.91(95%CI: 0.78 - 1.00), and 0.95
      (95%CI: 0.85 - 1.00), and efficiencies of 77.8%, 79.5% and 78.5% respectively.
      The time interval between ICU admission and CD8(+)CD28(+) positive 1.7 days
      (range: 1.0 - 7.0) was significantly shorter than the time to diagnosis of IFI by
      radiological 4.1 days (range: 1.0 - 21.0) and microbiological 7.5 days (range:
      3.0 - 17.0) criteria (P < 0.01). CONCLUSIONS: An extreme distribution of CD8(+) T
      lymphocyte subgroups in ICCI patients was closely related to PIFI. The
      measurement of CD8(+)CD28(+) T-cell counts may be an early predictor of PIFI in
      ICCI patients.

PMID- 22883064
TI  - [Clinical features and etiology of cholestasis in neonates].
AB  - OBJECTIVE: To explore the clinical features and etiology of cholestasis in
      neonates, and elucidate the difference between preterm and term infants. METHODS:
      A retrospective study was conducted for 176 cases of cholestasis during neonatal
      periods from January 2004 to December 2010 of Children's Hospital of Fudan
      University. Their etiologies included parenteral nutrition-associated cholestasis
      (PNAC), infection, biliary tract disorders, congenital abnormalities and
      chromosomal disorders, metabolic diseases, others (prenatal hypoxia, post
      unconjugated hyperbilirubinemia, neonatal lupus and congenital chylothorax) and
      unknown reasons. They were also divided into term and preterm groups according to
      gestational age, the relative factors, such as feeding patterns, use of
      parenteral nutrition (PN), infection and hypoxic history, and the clinical
      features, such as cholestasis onset age, bilirubin level, liver function and
      outcome were compared between two groups. RESULTS: The time of fasting, age of
      starting feeding, age of reaching to full feeding and the time of overall PN time
      were all longer in the preterm group than those in the term group (all P < 0.01).
      The preterm group had more PN and infection cases (all P < 0.05). The term group
      presented earlier with cholestasis and liver function damage versus the preterm
      group (both P < 0.05). The rate of recovery in term group is lower than in
      preterm group which is (62.9% (22/35) vs 82.3% (116/141), P = 0.014). The
      etiologies of 35 term infants were infection (n = 11, 31.4%), biliary tract
      disorders (n = 4, 11.4%), congenital abnormalities and chromosomal disorders (n =
      7, 20.0%), metabolic diseases (n = 3, 8.6%), others (n = 7, 20.0%) and unknown
      reasons (n = 3, 8.6%). There were 97 cases (68.8%) of PNAC in preterm infants and
      the average gestational age was 30(+4) (25(+3)-36(+2)) weeks. And the etiologies
      of the remaining 44 (31.2%) preterm cases without PNAC were infection (n = 21),
      biliary tract disorders (n = 3), metabolic diseases (n = 2), others (n = 5) and
      unknown reasons (n = 13). CONCLUSIONS: The etiologies of neonatal cholestasis are
      diverse. It may be more complicated in term and non-PNAC preterm infants. It is
      important to screen cholestasis in neonatal inpatients. Basic etiological
      elucidation and long-term follow-up are necessary for the positive cases.

PMID- 22883066
TI  - [Meta-analysis on the relationship between 25-hydroxyvitamin D level and
      hypertension].
AB  - OBJECTIVE: To explore the association between 25-hydroxyvitamin D level and
      hypertension so as to provide rationales for developing preventive strategies and
      understanding the etiology of hypertension. METHODS: The articles on the
      association of 25-hydroxyvitamin D level and hypertension were retrieved by
      searching international and national databases from 2000 to 2011. The
      relationship between 25-hydroxyvitamin D level and hypertension was assessed by
      Meta-analysis with Stata11.0 software. RESULTS: The results of Meta analysis
      showed that the pooled OR values of hypertension with 25-hydroxyvitamin D level
      deficiency and sufficiency was 1.37 (95%CI 1.23 - 1.53). Subgroup analysis
      revealed in 25-hydroxyvitamin D level, can be drawn between 25-hydroxyvitamin D
      level and the incidence of hypertension was statistically significant. The pooled
      OR values of hypertension with 25-hydroxyvitamin D level in 35 nmol/L and 35 - 68
      nmol/L were 2.02 (95%CI 1.49 - 2.74) and 1.23 (95%CI 1.02 - 1.49) (P < 0.05).
      CONCLUSIONS: The 25-hydroxyvitamin D level is associated with hypertension. With
      regards to the question of whether or not the 25-hydroxyvitamin D level
      deficiency serves as one of the potential risk factor for hypertension,
      prospective studies of larger sample sizes are warranted.

PMID- 22883065
TI  - [Efficacy and safety of sorafenib in the prevention and treatment of
      hepatocellular carcinoma recurrences after liver transplantation].
AB  - OBJECTIVE: To evaluate the efficacy and safety of sorafenib in the prevention and
      treatment of hepatocellular carcinoma (HCC) relapse after liver transplantation.
      METHODS: A retrospective cohort study was performed to assess the efficacy and
      safety of sorafenib for HCC. Forty-four patients who underwent liver transplant
      for HCC beyond Milan criteria form July 2007 to May 2010 were included study
      group (sorafenib, n = 22) and control group (without sorafenib, n = 22). The
      primary endpoints of the study were disease-free survival (DFS), overall survival
      (OS). Secondary outcomes included the rates of acute rejection and graft
      survival. RESULTS: The clinical data of 44 patients were completely collected.
      There were significantly differences between sorafenib group and control group in
      1-year DFS (81.8% (n = 18) vs 63.6% (n = 14), P < 0.05) and OS (90.9% (n = 20) vs
      72.7% (n = 16), P < 0.05) respectively. The acute rejection rates in Sorafenib
      were 13.6% (3/22), compared with 18.2% (4/22) in control group (P = 0.524) and 1
      year graft survival in Sorafenib group were 86.4% (19/22), compared with 72.7%
      (16/22) in control group (P = 0.086). The overall incidence of treatment-related
      adverse events was 68.1% (n = 15) in sorafenib group and 31.8% (n = 7) in the
      control group (P < 0.01). Adverse events that were reported for patients
      receiving sorafenib were predominantly grade 1 or 2 in severity including
      diarrhea (45.5%, n = 10), liver dysfunction (40.9%, n = 9), hand-foot skin
      reaction (31.8%, n = 7) and pains of head and four limbs (22.7%, n = 5). Two
      patients with grade 3 adverse events in study group were stopped continuing to
      use the sorafenib. Three patients with the dose of 400 mg twice daily and 17
      patients with the dose reduction of sorafenib continued to the study endpoint.
      CONCLUSION: Patients with HCC undergoing liver transplantation could get the
      benefits of Sorafenib in reducing the incidence of tumor recurrence and extending
      disease-free and overall survival time.

PMID- 22883067
TI  - [Clinical application of transcatheter embolization for Klippel-Trenaunay
      syndrome].
AB  - OBJECTIVE: To explore the feasibility of interventional treatment of Klippel
      Trenaunay syndrome(KTS). METHODS: The clinical data of 20 KTS patients admitted
      into our hospital from March 2005 to October 2010 were retrospectively analyzed.
      RESULTS: All 20 patients underwent angiography after the relevant examinations.
      Among them, 18 patients underwent interventional treatment (embolization with PVA
      particles and spring coils). Two patients received no interventional treatment
      due to non-cooperation, high risk or extremely thin vessels. And 18 patients
      achieved excellent results after interventional treatment. Neither complications
      nor peri-operative mortality occurred. The patients were followed-up for an
      average period of 12 months. Mild symptoms recurred in 2 patients. CONCLUSION:
      Interventional treatment is an effective, safe and mini-invasive procedure for
      KTS with satisfactory long-term outcomes.

PMID- 22883068
TI  - [Laparoscopic partial nephrectomy with highly selective clamping of renal
      arterial branches].
AB  - OBJECTIVE: To explore the feasibility and efficiency of new clamping technique of
      renal arterial branches during laparoscopic partial nephrectomy. METHODS: Between
      March and June 2011, 10 patients (6 males, 4 females) with small renal tumor
      underwent laparoscopic partial nephrectomy with highly selective clamping of
      renal arterial branches. The mean age was (47 +/- 13) years and the mean tumor
      size (2.8 +/- 0.9) cm. Operative duration, estimated blood loss, time for highly
      selective clamping of renal arterial branches, postoperative hospital stay,
      indwelling duration of drainage tube and complications were recorded. RESULTS:
      The operations were successfully performed in all patients. The mean operative
      duration was (101 +/- 23) min, the mean estimated blood loss 112 ml and the mean
      time for the clamping of renal arterial branches (28 +/- 6) min. There was
      neither blood transfusion nor conversion into open surgery. The mean indwelling
      duration of drainage tube was (5.0 +/- 1.3) days and the mean postoperative
      hospital stay(8.0 +/- 0.8)days. The recovery of all patients was uneventful.
      CONCLUSION: Highly selective clamping of renal arterial branches is a new method
      of protecting renal function during laparoscopic partial nephrectomy. Further
      studies and a longer follow-up are warranted.

PMID- 22883069
TI  - [Clinical analysis of drug-induced Pseudo-Bartter's syndrome: a report of five
      cases].
AB  - OBJECTIVE: To summarize the clinical characteristics and outcomes of Pseudo
      Bartter's syndrome and explore its pathogenesis. METHODS: The clinical data of 5
      cases of Pseudo-Bartter's syndrome at our ward from May 2008 to December 2010 was
      analyzed retrospectively. RESULTS: All patients were female. Long-term regimen of
      purgative or diuretics was prescribed. The clinical features included
      normotension, hypokalemic alkalosis and activation of renin-angiotensin
      aldosterone. The pathological results of 3 cases of kidney biopsy showed the
      hyperplasia of juxtaglomerular apparatus, thickness of arteriole, infiltration of
      lymphocytes and monocytes and degeneration of renal tubule. Upon a definitive
      diagnosis, purgative or diuretics was discontinued and supplement therapy of
      potassium chloride initiated. The results of laboratory tests reverted to normal
      ranges within 4 weeks. CONCLUSION: Purgative or diuretics should be prescribed
      appropriately to avoid the occurrence of Pseudo-Bartter's syndrome.

PMID- 22883070
TI  - [Effects of C-reactive protein on the expression of transforming growth factor
      beta1 and receptors on human renal tubular epithelial cells].
AB  - OBJECTIVE: To explore the effect of C-reactive protein (CRP) on the expression of
      Fcgamma receptors in human renal tubular epithelial cells and determine the role
      of Fcgamma receptors in CRP-induced expression of transforming growth factor
      beta1 (TGFbeta1). METHODS: Human renal tubular epithelial cells (HK-2) were
      cultured and stimulated with recombinant human CRP. The mRNA expression of
      Fcgamma receptors, including FcgammaRI (CD64), FcgammaRIIa (CD32a) and
      FcgammaRIII (CD16), was detected by real-time polymerase chain reaction (PCR). On
      the basis of real-time PCR results, CD32a was selected for further analysis: the
      CD32a expression in HK-2 cells incubated with 10 mg/L CRP for 24 h was determined
      by flow cytometry and Western blotting. HK-2 cells were preincubated with or
      without anti-CD32a IgG, followed by the addition of recombinant human CRP.
      Subsequently the biological effects of CRP were tested. TGFbeta1, type I collagen
      (ColI) and type IV collagen (ColIV) released into media were detected by enzyme
      linked immunosorbent assay. And TGFbeta1 mRNA expression was measured by real
      time PCR. RESULTS: On real-time PCR, CRP was found to significantly up-regulate
      the CD32a mRNA expression in HK-2 cells in a dose-dependent manner (P < 0.01).
      The peak up-regulation was observed at a dose of 10 mg/L. In contrast, mRNAs of
      CD16 and CD64 were not detected in HK-2 cells. Flow cytometry showed that CD32a
      expressed on HK-2 cells incubated with 10 mg/L recombinant human CRP for 24 h
      accounted for 23.35% +/- 7.43%, significantly higher than that on non-CRP-treated
      cells (1.66% +/- 0.28%, P < 0.01). Western blotting showed that CRP up-regulated
      CD32a expression in a dose-dependent manner. And 10 mg/L CRP induced the peak
      effect. Antibodies to CD32a inhibited the stimulatory effect of CRP on the
      generation of TGFbeta1, ColI and ColIV (all P < 0.05) and down-regulated the
      expression of TGFbeta1 mRNA (P < 0.01). CONCLUSION: The stimulation of CRP can
      significantly increase CD32a expression in renal tubular epithelial cells and up
      regulate the expression of transforming growth factor TGFbeta1 through CD32a
      receptor.

PMID- 22883071
TI  - [Control study on colonoscopy skills acquiring from endoscopic simulation system
      transfering to patients].
AB  - OBJECTIVE: To explore the feasibility of transferring the skills from the
      AccuTouch flexible endoscopy simulator colonoscopy training to clinical
      practices. METHODS: The novice colonoscopies were divided into 2 groups.Group A
      (control group) including 4 trainees for traditional training, Group B
      (experimental group) including 4 trainees for simulator training. After training,
      we compared the number of cases for achieving independent competence, assisted
      competence and incompetence in the first ten patients. RESULTS: No significant
      differences existed between two groups in terms of age and gender (both P >
      0.05). Significant differences existed in educational background and the
      controlled group was better than the experimental group (Z = -2.005, P = 0.04).
      The cases of independent completion, assisted competence and incompetence of the
      control and experimental groups were 2, 4, 9 and 21, 29, 15 respectively. Rank
      tests show that the simulator training was better than the traditional
      counterpart (average rank: 56.14 vs 24.86, Z = -6.393, P = 0.00). CONCLUSIONS:
      The skills acquired from AccuTouch Endoscopy Simulator may be well transferred
      into the clinical colonoscopy environment. It clearly supports the scheme of
      integrating simulator training into colonoscopic education curricula.

PMID- 22883072
TI  - First report of molecular diagnosis of Tunisian hemophiliacs A: identification of
      8 novel causative mutations.
AB  - INTRODUCTION: Hemophilia A is an X linked recessive hemorrhagic disorder caused
      by mutations in the F8 gene that lead to qualitative and/or quantitative
      deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of
      hemophilia A is challenging because of the high number of different causative
      mutations that are distributed throughout the large F8 gene. Molecular studies of
      these mutations are essential in order to reinforce our understanding of their
      pathogenic effect responsible for the disorder. AIM: In this study we have
      performed molecular analysis of 28 Tunisian hemophilia A patients and analyzed
      the F8 mutation spectrum. METHODS: We screened the presence of intron 22 and
      intron 1 inversion in severe hemophilia A patients by southern blotting and
      polymerase chain reaction (PCR). Detection of point mutations was performed by
      dHPLC/sequencing of the coding F8 gene region. We predict the potential
      functional consequences of novel missense mutations with bioinformatics
      approaches and mapping of their spatial positions on the available FVIII 3D
      structure. RESULTS: We identified 23 different mutations in 28 Tunisian
      hemophilia A patients belonging to 22 unrelated families. The identified
      mutations included 5 intron 22 inversions, 7 insertions, 4 deletions and 7
      substitutions. In total 18 point mutations were identified, of which 9 are
      located in exon 14, the most mutated exonic sequence in the F8 gene. Among the 23
      mutations, 8 are novel and not deposited in the HAMSTeRS database nor described
      in recently published articles. CONCLUSION: The mutation spectrum of Tunisian
      hemophilia A patients is heterogeneous with the presence of some characteristic
      features. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here:http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715.

PMID- 22883073
TI  - Influence of calcaneus angle and muscle forces on strain distribution in the
      human Achilles tendon.
AB  - BACKGROUND: Heterogeneous distribution of tendon strain is considered to
      contribute to the development of the Achilles tendon overuse injuries. Force
      distribution between the three portions of the triceps surae muscle and position
      of the calcaneus might affect the extent of strain differences within the
      Achilles tendon. Purpose of this study was to determine the effect of changes in
      force distribution within the triceps muscle and changes in calcaneus position on
      intratendinous strain distribution of the Achilles tendon. METHODS: Five
      cadaveric Achilles tendons including complete triceps surae and calcaneus were
      dissected. Specimens were mounted in a loading simulator allowing independent
      force application for the three parts of triceps muscle and changes calcaneus
      eversion and inversion position. Strain was determined in different aspects of
      the Achilles tendon. FINDINGS: Changes of calcaneus position resulted in
      intratendinous strain differences up to 15%, changes in force distribution within
      the triceps muscle resulted in strain differences up to 2.5%. Calcaneal eversion
      was connected to a higher degree of strain in medial tendon portions, while
      inversion increased strain in lateral tendon portions. INTERPRETATION: Medio
      lateral, proximo-distal and dorsal-ventral distribution of tendon strain is
      rather influenced by kinematics of the subtalar joint than by muscular imbalances
      within the triceps muscle. Clinical movement analyses should focus on motion
      pattern combining rearfoot eversion with high Achilles tendon load. The results
      indicate that twist of the Achilles tendon fascicles seems of paramount
      importance in balancing tendon strain. To get more insight into the Achilles
      tendon injuries pathogenesis future research should focus on methods monitoring
      heterogeneous distribution of strain in vivo.

PMID- 22883074
TI  - CPR skill retention of first aid attendants within the workplace.
AB  - INTRODUCTION: Immediate resuscitation is necessary in order to achieve conscious
      survival for persons who have lost airways or pulses. However, current literature
      suggests that even in medically-trained personnel, CPR skills are forgotten
      shortly after certification. HYPOTHESIS/PROBLEM: The purpose of this study was to
      determine the CPR skill and knowledge decay in those who are paid to respond to
      emergency situations within the workplace. METHODS: Using an unconscious victim
      scenario, the sequence and accuracy of CPR events were observed and recorded in
      244 participants paid to act as first responders in large industrial or service
      industry settings. RESULTS: A significant negative correlation was observed
      between days since training and a pre-CPR safety check variable, periodic checks
      for breathing and positioning. Many of the knowledge-related assessment skills
      (e.g., scene safety, emergency medical system (EMS) activation) appeared to
      deteriorate with time, although they could be contaminated by the repetition of
      training in those who had recertified one or more times. Skill-based components
      such as landmarking for chest compressions and controlling the airway declined in
      a more predictable fashion. CONCLUSION: The results of this study suggest that
      repetition may be more important than days since last trained for skill and
      knowledge retention, and methods of "refreshing" skills should be examined. While
      skills deteriorate rapidly, changing frequency of certification is not
      necessarily the best way to increase retention of skill and knowledge.

PMID- 22883075
TI  - When time is about to run out ... but not really.

PMID- 22883076
TI  - Managing cardiovascular risk in rheumatoid patients.

PMID- 22883077
TI  - Relation of improvement in glomerular filtration rate with atorvastatin to
      reductions in heart failure morbidity.

PMID- 22883078
TI  - Free flaps in elderly patients: outcomes and complications in head and neck
      reconstruction after oncological resection.
AB  - INTRODUCTION: Free flaps represent the first reconstructive option for many head
      and neck defects. The increasing life expectancy of the population results in
      increasing numbers of ageing patients facing complex reconstructive surgery. In
      this study we evaluated our experience with free-flap transfers in older
      patients, analysing the post-operative reconstructive and systemic complications.
      MATERIALS AND METHODS: Between 2000 and 2009, 360 patients underwent free flap
      reconstruction of defects resulting from the treatment of head and neck tumours
      at the Operative Unit of Maxillofacial Surgery, University - Hospital of Parma,
      Italy. Fifty-five patients (15.3%) were more than 75 years old at the time of
      treatment. RESULTS: At the end of the follow-up successful free-flap transfer was
      achieved in 360 of the 373 flaps harvested (96.5%). The overall reconstructive
      complication rate was 31.4%, (31.8% in the younger group and 29.1% in the
      remaining patients). Medical complications were observed in 29.2% of cases (less
      than 75 years: 28.8%; more than 75 years: 30.9%). The ASA status was associated
      with a statistically significantly higher incidence of complications within
      patients less than 75 years old (p < 0.0001). DISCUSSION AND CONCLUSIONS: The
      results of this study, in agreement with previous studies, provide evidence that
      free-tissue transfer may be performed in ageing patients with a high degree of
      technical success. The chronologic age cannot be considered an appropriate
      criterion in the reconstructive decision. On the contrary, a careful selection of
      the patients based on comorbidities and general conditions (ASA status) is of
      primary importance in reducing post-operative complications and to improving the
      results of surgery.

PMID- 22883079
TI  - Comparison of male and female lower limb segment inertial properties.
AB  - Many studies have examined human segmental inertial parameters, but these studies
      have focused more on male rather than female data. The purpose of this study was
      to determine the lower limb segmental inertial parameters for a large sample
      (n>1500) of both males and females. The participants in this study were those
      measured as part of a survey of the anthropometry of US army personnel. The
      sample comprised 1774 males (mean height 1.756+/-0.079 m, mean mass of 78.49+/
      0.11 kg, and mean age of 27.21+/-6.81 years), and 2208 females (mean height
      1.629+/-0.072 m, mean mass of 62.01+/-0.08 kg, and mean age of 26.18+/-5.70
      years). Anthropometric measurements were used to determine the inertial
      properties of the lower limb segments by modeling them as series of geometric
      solids. An analysis of variance revealed that the normalized inertial parameters
      for each of the segments were statistically significantly different (p>0.001)
      between the two groups. The time for each segment to swing through the range of
      motion of the swing phase of gait, produced shorter swing times for the male
      segments. The differences between the segmental inertial properties for the sexes
      have implications for how these parameters are customized to experimental
      subjects.

PMID- 22883080
TI  - Patient-specific bone modelling and remodelling simulation of hypoparathyroidism
      based on human iliac crest biopsies.
AB  - We previously developed a load-adaptive bone modelling and remodelling simulation
      model that can predict changes in the bone micro-architecture as a result of
      changes in mechanical loading or cell activity. In combination with a novel
      algorithm to estimate loading conditions, this offers the possibility for patient
      specific predictions of bone modelling and remodelling. Based on such models, the
      underlying mechanisms of bone diseases and/or the effects of certain drugs and
      their influence on the bone micro-architecture can be investigated. In the
      present study we test the ability of this approach to predict changes in bone
      micro-architecture during hypoparathyroidism (HypoPT), as an illustrative
      example. We hypothesize that, apart from reducing bone turnover, HypoPT must also
      lead to increased osteocyte mechanosensitivity in order to explain the changes in
      bone mass seen in patients. Healthy human iliac crest biopsies were used as the
      starting point for the simulations that mimic HypoPT conditions and the resultant
      micro-architectures were compared to age-matched clinical HypoPT biopsies.
      Simulation results were in good agreement with the clinical data when osteocyte
      mechanosensitivity was increased by 40%. In conclusion, the results confirm our
      hypothesis, and also demonstrate that patient-specific bone modelling and
      remodelling simulations are feasible.

PMID- 22883082
TI  - [Guideline of non-ST segment elevation acute coronary syndrome].

PMID- 22883081
TI  - Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5
      HT(1) (B)  receptors via the Raf/ERK/MAPK pathway in rats.
AB  - AIM: Cigarette smoke exposure increases the risk of stroke. Upregulation of 5
      hydroxytryptamine 1B (5-HT(1) (B) ) receptors is associated with the pathogenesis
      of cerebral ischaemia. This study examined the hypothesis that the expression of
      5-HT(1) (B) receptors is altered in brain vessels after secondhand smoke (SHS)
      exposure. METHODS: Rats were exposed to SHS in vivo for 200 min daily for 8
      weeks. The contractile responses of isolated cerebral arteries were studies by a
      sensitive myograph. The mRNA and protein expression for 5-HT(1) (B) receptors
      were examined by real-time PCR, Western blot and immunofluorescence respectively.
      In addition, the phosphorylation of Raf/extracellular signal-regulated kinase
      (ERK)/mitogen-activated protein kinases (MAPK) pathway was evaluated. RESULTS:
      The results showed that SHS exposure shifted the 5-HT(1) (B) receptor-mediated
      concentration-contraction curve towards the left with a markedly increased
      maximal contraction. Furthermore, there were significant elevations in mRNA level
      and protein expression of 5-HT(1) (B) receptors in SHS-exposed rats.
      Immunostaining revealed that the 5-HT(1) (B) receptors were localized to the
      smooth muscle cells of cerebral arteries. SHS was also found to induce the
      phosphorylation of Raf-1 and ERK1/2 proteins. The administration of a Raf-1
      inhibitor GW5074 attenuated the 5-HT(1) (B) receptor upregulation. CONCLUSION:
      Secondhand smoke exposure upregulates cerebrovascular 5-HT(1) (B) receptors in
      rats. The receptor upregulation is associated with Raf/ERK/MAPK activation.

PMID- 22883084
TI  - [Re-evaluation on the adverse effects of statins].

PMID- 22883083
TI  - [Systemic lupus erythematosus and premature atherosclerosis].

PMID- 22883085
TI  - [Relationship between plasma N-terminal pro-brain natriuretic peptide and GRACE
      risk stratification in non-ST-segment elevation acute coronary syndrome].
AB  - OBJECTIVE: To explore the relationship between plasma N-terminal pro-brain
      natriuretic peptide (NT-proBNP) level obtained on admission and global registry
      of acute coronary events (GRACE) scores and the value for risk stratification in
      patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
      METHODS: A total of 231 NSTE-ACS patients admitted in our hospital between June
      2009 and September 2010 were included [161 patients with unstable angina (UA) and
      70 patients with non-ST-segment elevation myocardial infarction (NSTEMI)]. On
      admission plasma NT-proBNP was measured in all patients. The GRACE risk score
      were used for risk assessment. Patients were followed up for 6 months and
      incidence of new or recurrent myocardial infarction, target vessel
      revascularization, cardiac death, heart failure (MACE) was recorded. RESULTS:
      According to GRACE risk stratification, there were 62 low-risk patients, 78
      middle-risk patients and 91 high-risk patients. lgNT-proBNP level on admission
      increased in proportion to increasing risk defined by GRACE risk stratification
      and lgNT-proBNP positively correlated with GRACE risk score (r = 0.59, P <
      0.001). The GRACE risk score was the highest in the fourth NT-proBNP quartile (P
      < 0.001 vs. lowest, second and third quartiles). GRACE score was significantly
      higher in patients with NT-proBNP level above the 75 percentile compared patients
      with NT-proBNP under the 75 percentile (P < 0.001). MACE occurred in 9 [3.9%
      (9/231)] patients during follow up. ROC analysis showed AUC of on admission NT
      proBNP was 0.831 (SE = 0.062, P = 0.001, 95%CI 0.711 - 0.952) and AUC of GRACE
      risk score was 0.799 (SE = 0.079, P = 0.002, 95%CI 0.644 - 0.954) for predicting
      the short-term risk of MACE (P = 0.75). CONCLUSION: On admission plasma NT-proBNP
      level parallels GRACE risk score in NSTE-ACS patients, both on admission plasma
      NT-proBNP level and GRACE risk score are valuable parameters for risk
      stratification in patients with NSTE-ACS and increased NT-proBNP level and GRACE
      values are predictors for increased short-term risk of MACE.

PMID- 22883086
TI  - [Clinical manifestations of patients with systemic lupus erythematosus and
      coronary artery disease].
AB  - OBJECTIVE: To analyze the clinical characteristics of patients with systemic
      lupus erythematosus (SLE) and coronary artery disease (CAD). METHODS: Clinical
      data of 3911 SLE patients were retrospectively analyzed and CAD was diagnosed by
      coronary angiography in 26 (0.7%) SLE patients (10 stable angina pectoris, 5
      unstable angina pectoris, 8 STEMI and 3 non-STEMI). The tradition risk factors,
      first onset of cardiac events, blood biochemistry index, treatment and activity
      of SLE, coronary angiographic features were compared with 552 CAD patients
      without SLE. RESULTS: Compared with CAD patients without SLE, CAD patients with
      SLE were younger [(50.4 +/- 15.2) years vs. (60.6 +/- 11.6) years, P < 0.01], the
      mean number per patient of Framingham tradition risk factors was less (1.11 +/-
      1.18 vs. 2.50 +/- 1.28, P < 0.05). CAD patients with SLE were prone to premature
      coronary artery disease [76.9% (20/26)], and ACS was the most common
      manifestation in SLE patients with premature coronary artery disease [65.0%
      (13/20)], the duration of steroid use was significantly longer [24.00 (3.75,
      57.00) months vs. 1.00 (0.00, 2.00) months, P < 0.05] and 24 hours total urine
      protein [(1.93 +/- 1.97) g vs. (0.76 +/- 0.75) g, P < 0.05] was significantly
      higher in the ACS patients with SLE than non-ACS patients with SLE. Coronary
      stenosis was evidenced in most of the SLE patients with CAD [76.9% (20/26)] and
      incidence of coronary thrombotic occlusion was significantly higher in SLE
      patients with CAD than CAD patients without SLE [30.8% (8/26) vs. 11.8% (65/552),
      P < 0.05]. CONCLUSION: The incidence of CAD in SLE patients is low and the major
      form of CAD in SLE patients is premature coronary artery disease and mostly
      induced by coronary thrombotic occlusion.

PMID- 22883087
TI  - [Clinical and coronary features of systemic lupus erythematosus patients with
      coronary artery disease].
AB  - OBJECTIVES: To observe the clinical and coronary features of patients with
      systemic lupus erythematosus (SLE) and coronary artery disease (CAD). METHODS:
      Among 2877 SLE inpatients (age >= 18 years, male 363, female 2514) admitted in
      the Peking Union Medical College Hospital between January 1999 to October 2009,
      33 patients [mean age (50.7 +/- 12.8) years] were diagnosed with CAD and coronary
      angiogram was available in 20 out of these 33 patients. Clinical and coronary
      features of these patients were retrospectively reviewed. RESULTS: The incidence
      of CAD was significantly higher in male SLE patients than in female patients
      [2.48% (9/363) vs. 0.95% (24/2514), P = 0.022]. Patients with secondary
      antiphospholipid syndrome were more likely to suffer from CAD [5.76% (8/139) vs.
      0.91% (25/2738), P < 0.001]. Myocardial infarction was the major form of CAD
      (24/33). Coronary artery angiographic changes included coronary stenosis and
      occlusions, coronary aneurysms and acute thrombosis and multi-vessel lesions was
      found in 75.0% (15/20) patients with SLE and CAD. CONCLUSIONS: Male SLE patients
      and patients with secondary antiphospholipid syndrome are at higher risk for CAD.
      Myocardial infarction and multi-vessel lesions are common in SLE patients with
      CAD.

PMID- 22883088
TI  - [Association study on the microRNA-1 target gene polymorphism and the risk of
      premature coronary artery disease].
AB  - OBJECTIVE: To investigate the association between the genetic variant of miRNA-1
      target gene COG6 rs9548934 C->T and the risk of premature coronary artery disease
      (pCAD). METHODS: This study included 226 pACD patients and 275 gender and age
      matched pCAD-free controls hospitalized in our hospital, diagnosis was made based
      on coronary angiography (CAG) results. The genotypes of miRNA-1 target gene COG6
      rs9548934 C->T were detected by PCR-RFLP. RESULTS: Compared with the wide
      genotype CC, subjects with the variant genotypes CT of rs9548934 C->T was
      associated with a 45% lower risk of pACD (adjusted OR = 0.55, 95%CI = 0.36 -
      0.82, P = 0.003), and the subjects with CT/TT genotypes were also associated with
      a significantly lower risk of pACD (adjusted OR = 0.64, 95%CI = 0.44 - 0.92, P =
      0.015). Using the median serum TG level (1.20 mmol/L) in control group as the
      cutoff value, subjects with higher serum TG levels were associated with increased
      risk of pACD after adjustment for age, gender and BMI (adjusted OR = 2.32, 95%CI
      = 1.57 - 3.41, P < 0.001). In addition, subjects with higher HDL-C levels were
      associated with significantly lower risk of pACD (adjusted OR = 0.48, 95%CI =
      0.31 - 0.75, P = 0.001). Stratified analyses showed that the risk reduction for
      pCAD in CT/TT genotypes carriers was more significant in the female subjects
      (adjusted OR = 0.54, 95%CI = 0.30 - 0.97, P = 0.040), and in subjects with lower
      TG, TC, HDL-C and LDL-C levels (adjusted OR = 0.62, 95%CI = 0.39 - 0.98, P =
      0.040; adjusted OR = 0.55, 95%CI = 0.35 - 0.85, P = 0.008; adjusted OR = 0.43,
      95%CI = 0.22 - 0.87, P = 0.018; adjusted OR = 0.49, 95%CI = 0.32 - 0.75, P =
      0.001, respectively). CONCLUSION: The polymorphism of miRNA-1 target gene COG6
      rs9548934C->T is associated with lower risk of pCAD, especially in female
      subjects and subjects with lower serum lipid levels.

PMID- 22883089
TI  - [Effects of myocardial platelet rich plasma injection on rats with acute
      myocardial infarction:(99)Tc(m)-MIBI gated SPECT imaging evaluation results].
AB  - OBJECTIVE: To observe the effect of direct myocardial injection of platelet rich
      plasma (PRP) on cardiac function, ventricular remodeling and myocardial
      perfusion. METHODS: Myocardial infarction was induced in 30 Fisher rats by left
      anterior descending coronary artery (LAD) ligation. One week after LAD ligation,
      rats in control group (n = 15) received 0.5 ml saline myocardial injection and
      rats in PRP group (n = 11) received 0.5 ml PRP myocardial injection.(99)Tc(m)
      methoxyisobutylisonitrile (MIBI) gated single photon-emission computed tomography
      (SPECT) imaging was applied at 1 week post LAD ligation and prior myocardial
      saline/PRP injection and repeated at 4 week post LAD ligation to assess
      myocardial perfusion and ejection fraction (EF), left ventricular end-diastolic
      volume (LVEDV), left ventricular end-systolic volume (LVESV), and the number of
      infarct segments. RESULTS: EF remained unchanged between 1 and 4 weeks post LAD
      ligation in control group and was significantly higher at 4 weeks post LAD
      ligation than at 1 week post LAD ligation in PRP group (P < 0.05). LVESV was
      significantly increased in the control group (P < 0.05) while remained unchanged
      in the PAP group (P < 0.05) at 4 weeks post LAD ligation compared that at 1 week
      post LAD ligation. LVEDV remained unchanged in the control group (P > 0.05) and
      significantly increased in the PRP group (P < 0.05) from 1 week to 4 weeks post
      LAD ligation. Myocardial perfusion remained unchanged in the control group and
      significantly improved in the PRP group at 4 week post LAD ligations.
      Histological examination also confirmed that PRP treatment can decrease infarct
      size [from (47 +/- 19)% to (36 +/- 11)%], increase ventricular wall thickness
      [from (3.1 +/- 0.9) mm to(4.6 +/- 1.8) mm] (P < 0.05). CONCLUSION: Myocardial PRP
      injection could improve cardiac function and reperfusion in this rat model of
      acute myocardial infarction.

PMID- 22883090
TI  - [Impact of metabolic syndrome on cardio-cerebral vascular events in pre
      hypertensive population].
AB  - OBJECTIVE: This study investigated the impact of metabolic syndrome on the
      development of cardio-cerebral vascular (CVD) events in a pre-hypertensive
      population. METHODS: The data used in this prospective study was derived from the
      Kailuan study cohort (n = 101 510). Prehypertension was diagnosed in 29 968 (mean
      age: 50 +/- 9 years and 23 744 males) individuals by the JNC VII criteria and
      these subjects were further classified into metabolic syndrome positive (MS+, n =
      3447) and MS negative (MS-, n = 26 521) groups according to the modified 2004
      Chinese Diabetes Society criteria. Subjects were followed up for 38 - 53 (mean 47
      +/- 5) months and first-ever CVD events were recorded. Baseline anthropometric
      and laboratory features were obtained by physical examination from June 2006 to
      October 2007 and the last follow-up day was December 31, 2010. Multivariable Cox
      proportional hazards regression models were used to analyze the risk factors of
      first-ever CVD events. RESULTS: There were 354 CVD events during follow up. The
      incidences of CVD events (1.80% vs. 1.28%) and cerebral infarction (1.10% vs.
      0.57%) were significantly higher in the MS+ group than in the MS- group (all P <
      0.05). After adjustment for other established CVD risk factors, the hazards ratio
      was 1.45 (95%CI: 1.10 - 1.92) for total CVD events and 1.84 (95%CI: 1.27 - 2.67)
      for cerebral infarction events in MS+ group. CONCLUSIONS: In this cohort,
      metabolic syndrome is linked with increased risk for CVD events.

PMID- 22883091
TI  - [Metalloproteinase Tolloid-like 1 gene mutation in Chinese patients with sporadic
      congenital heart diseases].
AB  - OBJECTIVE: To explore whether there are gene mutations of Tolloid-like 1 (TLL-1)
      gene in Chinese patients with sporadic congenital heart disease (CHD). METHODS:
      One hundred and fifteen patients with sporadic CHD were selected as CHD group.
      One hundred and two age and gender-matched healthy people were recruited as
      control group. After amplifying the exon 10 of the TLL-1 gene by polymerase chain
      reaction, the polymerase chain reaction products were purified, sequenced and
      analyzed in order to investigate the TLL-1 gene mutation. RESULTS: An insertion
      mutation of base A in the exon 10 of TLL-1 gene was identified in 7 out of 115
      CHD patients, including 3 patients with atrial septal defect, 2 patients with
      ventricular septal defect, 1 patients with patent ductus arteriosus and 1
      patients with complex CHD, the total mutation rate was 6.1% in CHD group and 0 in
      control group (P < 0.01). CONCLUSIONS: TLL-1 gene mutation with an insertion
      mutation of base A in exon 10 is often in Chinese patients with various CHD. The
      underlying pathogenesis between TLL-1 gene mutation and occurrence of congenital
      heart disease in Chinese people remains unclear and warrants further
      investigations.

PMID- 22883092
TI  - [MicroRNAs expression in normal and dissected aortic tissue].
AB  - OBJECTIVES: To investigate if there is altered microRNAs (miRNAs) expression in
      aortic dissection (Debakey Type A) and normal aorta tissue. METHODS: Total RNA
      was exacted from aorta of 5 patients with aortic dissection (AD) and four
      patients without aortic diseases (NA). miRNAs of the aortic tissues were analyzed
      by miRNA microarray. Reverse transcription polymerase chain reaction (RT-PCR) was
      performed to verify the expression of miRNAs in larger sample size (AD = 11 and
      NA = 9). RESULTS: hsa-miR-146b-5p_st, hsa-miR-19a_st and hsa-miR-505_st were
      significantly upregulated while hsa-miR-1268_st and hsa-miR-939_st were
      significantly downregulated [fold change > 2, q-value (%) <= 5] in AD group
      compared with NA group. RT-PCR verified hsa-miR-146b-5p_st miRNAs change in AD
      group. CONCLUSIONS: Altered miRNAs expression might play an essential role in the
      pathogenesis of aortic dissection formation and hsa-miR-146b-5p_st might serve as
      a new diagnosis biomarker of aortic dissection.

PMID- 22883093
TI  - [Role of triggering receptor expressed on myeloid cells-1 on coxsackievirus B3
      induced inflammation and cardiomyocyte injury].
AB  - OBJECTIVE: To determine the expression of TREM-1 (triggering receptor expressed
      on myeloid cells-1) in macrophages after coxsackievirus B3 (CVB3) infection and
      the cardiomyocytes viability after culturing with supernatant of macrophages in
      the absence and presence of TREM-1 inhibitor LP-17 to explore if TREM-1 is
      involved in the pathogenesis of CVB3 infection induced inflammation and
      cardiomyocytes injury. METHODS: TREM-1 mRNA and TREM-1 and DAP-12 protein
      expression in macrophages were detected by Real-time PCR at 0, 1, 4, 8 and 12 h
      and by Western blot at 0, 16, 24 and 48 h post CVB3 infection. TNF-alpha
      secretion of macrophages was measure by ELISA, vitality and the apoptosis degree
      of cardiomyocytes was assessed by CCK8 and Annexin V-FITC after the
      cardiomyocytes were cultured with the supernatant of macrophages in normal
      control group, CVB3 infection group and LP-17 pretreated CVB3 infection group.
      RESULTS: TREM-1 mRNA expression was significantly upregulated at 4, 8, and 12 h
      (peaked at 8 h) and TREM-1 protein expression was significantly upregulated at 16
      and 24 h and returned to baseline level at 48 h after CVB3 infection. The protein
      expression of DAP-12, a direct downstream signaling molecule of TREM-1, also
      significantly increased at 24 and 48 h post CVB3 infection (P < 0.01). Level of
      macrophages secreted TNF-alpha post CVB3 infection was significantly reduced in
      LP-17 pretreated cells (P < 0.01), LP-17 pretreatment also significantly improved
      viability and significantly reduced apoptosis of cardiomyocytes cultured with
      supernatant of CVB3 infected macrophages (P < 0.01). CONCLUSION: TREM-1 might be
      an important mediator post CVB3 infection and a major player on inducing excess
      macrophages-related inflammation and resulting in an indirect injury to
      cardiomyocytes.

PMID- 22883094
TI  - [Expression of extracellular matrix metalloproteinase inducer in the unstable
      plaque of patients with acute coronary syndrome].
AB  - OBJECTIVE: To observe the expression of extracellular matrix metalloproteinase
      inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome
      (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in
      macrophages. METHODS: The EMMPRIN expression was detected by immunohistochemistry
      in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was
      evaluated by Western blot on macrophages differentiated from THP-1 which were
      stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There
      are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6
      macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L)
      for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L
      U75302 2 h before the LTB4 (10(-7) mol/L) stimulation. RESULTS: Abundant EMMPRIN
      expression was detected in macrophages and smooth muscle cells of unstable
      plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN
      expression was significantly upregulated in a concentration-dependent manner in
      LTB4 stimulated groups, which was significantly higher in group 3-6 than in the
      THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and
      pretreatment with U75302 significantly reduced the LTB4 induced upregulation of
      EMMPRIN in a dose-dependent manner (P < 0.05). CONCLUSION: EMMPRIN expression is
      enhanced in macrophages and smooth muscle cells on unstable coronary artery
      plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1
      derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in
      the formation and progression of unstable plaques, future studies are warranted
      to explore if LTB4 and EMMPRIN antagonists are effective or not for treating
      patients with ACS.

PMID- 22883095
TI  - [Acute pulmonary thromboembolism without D dimmer elevation in one patient].

PMID- 22883096
TI  - [Effects of docosahexaenoic acid on ion channels of rat coronary artery smooth
      muscle cells].
AB  - OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on large
      conductance Ca(2+)-activated K(+) (BK(Ca)) channels and voltage-dependent K(+)
      (K(V)) channels in rat coronary artery smooth muscle cells (CASMCs), and evaluate
      the vasorelaxation mechanisms of DHA. METHODS: BK(Ca) and K(V) currents in
      individual CASMC were recorded by patch-clamp technique in whole-cell
      configuration. Effects of DHA at various concentrations (0, 10, 20, 40, 60 and 80
      umol/L) on BK(Ca) and K(V) channels were observed. RESULTS: (1) DHA enhanced
      IBK(Ca) and BK(Ca) tail currents in a concentration-dependent manner while did
      not affect the stably activated curves of IBK(Ca). IBK(Ca) current densities were
      (68.2 +/- 22.8), (72.4 +/- 24.5), (120.4 +/- 37.9), (237.5 +/- 53.2), (323.6 +/-
      74.8) and (370.6 +/- 88.2)pA/pF respectively (P < 0.05, n = 30) with the addition
      of 0, 10, 20, 40, 60 and 80 umol/L DHA concentration, and half-effect
      concentration (EC(50)) of DHA was (36.22 +/- 2.17)umol/L. (2) IK(V) and K(V) tail
      currents were gradually reduced, stably activated curves of IK(V) were shift to
      the right, and stably inactivated curves were shifted to the left in the presence
      of DHA. IK(V) current densities were (43.9 +/- 2.3), (43.8 +/- 2.3), (42.9 +/-
      2.0), (32.3 +/- 1.9), (11.7 +/- 1.5) and (9.6 +/- 1.2)pA/pF respectively(P <
      0.05, n = 30)post treatment with 0, 10, 20, 40, 60 and 80 umol/L DHA under
      manding potential equal to +50 mV, and EC(50) of DHA was (44.19 +/- 0.63)umol/L.
      CONCLUSION: DHA can activate BK(Ca) channels and block K(V) channels in rat
      CASMCs, the combined effects on BK(Ca) and K(V) channels lead to the vasodilation
      effects of DHA on vascular smooth muscle cells.

PMID- 22883097
TI  - [Epidemiological survey on pre-hypertension and hypertension prevalence among
      adolescents aged 11 to 17 years in Shanghai].
AB  - OBJECTIVE: To assess the prevalence of pre-hypertension and hypertension as well
      as the association with overweight/obesity in Shanghai adolescents. METHODS:
      School children aged 11 - 17 years in four schools in Shanghai were included in
      this survey. All students were visited in May 2010 at school by trained nurses or
      physicians who administered a questionnaire and carried out anthropometric
      measurements. Anthropometric measurements included height, weight, heart rate and
      blood pressure. Repeat measurements were performed in school children with
      elevated blood pressure within one month. The pre-hypertension and hypertension
      was defined on the basis of the 2004 National High Blood Pressure Education
      Program Working Group definitions. The overweight and obesity was defined using
      cutoff points recommended by Working Group of Obesity, China (WGOC). RESULTS:
      There were 4175 school children aged 11 - 17 years [mean (15.0 +/- 1.9) years,
      52.3% (n = 2183) girls and 47.7% (n = 1992) boys]. There were 72.5% (n = 3025)
      participants with normal blood pressure [ girls (n = 1666) 76.3% and boys (n =
      1361) 68.3%], 18.0% (n = 750)participants with pre-hypertension [14.2% (n = 310)
      for girls and 22.1% (n = 440) for boys], 8.3% (n = 346) participants with stage 1
      hypertension [8.2% (n = 179) for girls and 8.3% (n = 165) for boys] and 1.3% (n =
      54) participants with stage 2 hypertension [1.3% (n = 28) for girls and 1.3% (n =
      26) for boys]. The prevalence of overweight and obesity was 6.7% (n = 147) and
      3.0% (n = 66) for girls and 13.7% (n = 273) and 6.3% (n = 125) for boys. After
      adjusting for gender, age, parental history of hypertension and physical
      activities, multivariable logistic regression analysis showed that the overweight
      [adjusted odds ratio and 95% confidence interval: 1.42 (1.16 - 1.75)] and obesity
      [adjusted odds ratio and 95% confidence interval: 2.35 (1.78 - 3.11)] were
      independent predictors of elevated blood pressure in this cohort. CONCLUSIONS:
      The prevalence of elevated blood pressure is common in adolescents in Shanghai.
      Overweight and obesity are closely associated with the elevated blood pressure in
      this cohort.

PMID- 22883098
TI  - [Plasma lipid level and incidence of dyslipidemia in workers of Chongqing
      enterprises and institutions].
AB  - OBJECTIVE: To examine the plasma lipid level and distribution of dyslipidemia in
      workers of Chongqing enterprises and institutions. METHODS: By using cluster
      sampling method, 20 000 workers of Chongqing enterprises and institutions aged 18
      to 60 were selected as target population from January to October, 2009. We
      conducted questionnaire survey, physical and laboratory examinations including
      total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol
      (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Workers were divided
      into 18 - 29 years old group, 30 - 39 years old group, 40 - 49 years old group
      and 50 - 60 years old group. Characteristic and distribution of dyslipidemia were
      analyzed. RESULTS: Total cholesterol (TC), triglyceride (TG), high-density
      lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)
      were significantly different in various age group (all P < 0.01). TC, TG, HDL-C
      and LDL-C levels in the 30 years and over groups were all significantly higher
      than in the under 30 years old group(all P < 0.01). The TG levels in the 40 - 49
      years old group and the 50 - 60 years old group were similar (P > 0.05). After
      adjusting for age, TC, TG, HDL-C and LDL-C levels in males were all significantly
      higher than in females (all P < 0.01). The incidence of dyslipidemia in this
      population was 35.01% and significantly higher in males than that of females
      (58.27% vs. 11.01%, P < 0.01). The incidence of dyslipidemia increased with aging
      (P < 0.01). CONCLUSIONS: The prevalence of dyslipidemia is high in Chongqing
      enterprises and institutions. The incidence of dyslipidemia is higher in males
      than in females and higher among the 30 years and over workers than that of under
      30 years old workers.

PMID- 22883099
TI  - [One case of acute coronary syndrome caused by prosthetic aortic valve
      dysfunction].

PMID- 22883100
TI  - [Electrocardiograph resembles acute ST segment elevation myocardial infarction in
      pheochromocytoma crisis: a case report].

PMID- 22883101
TI  - [Association between C-reactive protein gene polymorphisms/haplotypes and serum
      levels and related diseases].

PMID- 22883102
TI  - [Advances of experimental vaccination for prevention and treatment of
      atherosclerosis].

PMID- 22883103
TI  - Simultaneous determination of active flavonoids and alkaloids of Tang-Min-Ling
      Pill in rat plasma by liquid chromatography tandem mass spectrometry.
AB  - A rapid, sensitive and reliable liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method was developed and validated for simultaneous determination of
      five active flavonoids (wogonin, chrysin, oroxylin A, naringenin, hesperetin) and
      four major alkaloids (berberine, coptisine, jatrorrhizine, palmatine) from Tang
      Min-Ling-Pill in rat plasma. Plasma samples (100 MUL) were spiked with internal
      standards daidzein (for flavonoids) and tetrahydropalmatine (for alkaloids),
      acidified with HCl and extracted by liquid-liquid extraction with acetone.
      Chromatographic separation was performed on a Zorbax SB-C(18) column with the
      mobile phase of water (containing 0.1% of formic acid)-acetonitrile (30:70, v/v)
      at a flow rate of 0.3 mL/min in a run time of 7.0 min. Detection was performed by
      multiple reaction monitoring mode using electrospray ionization in the positive
      ion mode. All analytes showed good linearity over the investigated concentration
      range (r>0.9900). The validated lower limit of quantification was 1.01 ng/mL for
      wogonin and oroxylin A, 0.238 ng/mL for chrysin, 1.01 ng/mL for naringenin, 0.998
      ng/mL for hesperetin, 0.0505 ng/mL for berberine, 0.0996 ng/mL for coptisine,
      0.0501 ng/mL for jatrorrhizine, 0.0889 ng/mL for palmatine, respectively. Intra-
      and inter-day precision (RSD%) was less than 15% and accuracy (RE%) ranged from 
      7.5% to 4.5%. The validated method was successfully applied to investigate the
      pharmacokinetics of the major flavonoids and alkaloids of Tang-Min-Ling-Pill
      after oral administration to rats.

PMID- 22883104
TI  - Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after
      human lung transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow
      obstruction that affects a majority of lung transplant recipients and limits long
      term posttransplant survival. Although epithelial injury appears central to the
      development of BOS, little is known regarding the specific epithelial cell types
      that are affected in this condition. We hypothesized that BOS would involve
      preferential injury to the secretory Clara cells that function in innate defense
      and epithelial repair. To test this hypothesis, we assessed tissue transcript,
      tissue protein and lung fluid protein expression of Clara cell secretory protein
      (CCSP), a marker for Clara cells, in lung transplant recipients with BOS, BOS
      free patients and in donor controls. Our results demonstrate that CCSP tissue
      transcript and protein expression are significantly reduced in lung transplant
      recipients with BOS compared to BOS-free or donor controls. In addition, we
      demonstrate that CCSP protein levels are significantly reduced in the lung fluid
      of patients with BOS compared to BOS-free controls, in cross-sectional and
      longitudinal analysis. Collectively, these complementary results illustrate that
      BOS involves a selective alteration in the distribution and function of
      bronchiolar Clara cells.

PMID- 22883105
TI  - Prediction of metabolic syndrome among postmenopausal Ghanaian women using
      obesity and atherogenic markers.
AB  - BACKGROUND: Metabolic syndrome (MetS) is an important health problem which puts
      individuals at risk for cardiovascular diseases and type 2 diabetes as well as
      obesity-related cancers such as colon and renal cell in men, and endometrial and
      oesophageal in women. OBJECTIVE: This study was aimed at examining how obesity
      indicators and related determinants influence metabolic syndrome, and how the
      factors can be used to predict the syndrome and its cut-offs in postmenopausal
      Ghanaian women. METHODS: Two hundred and fifty (250) Ghanaian subjects were
      involved in the study with one hundred and forty-three (143) being premenopausal
      women and one hundred and seven (107) postmenopausal women. The influence of
      traditional metabolic risk factors including high blood pressure, dyslipidemia
      and glucose intolerance on obesity and atherogenic indices i.e. body mass index
      (BMI), waist circumference (WC), waist-to-hip ratio (WHR), Waist-to-thigh ratio
      (WTR), waist-to-height ratio (WHtR), high density lipoprotein cholesterol to
      total cholesterol ratio (HDL-C/TC), high density lipoprotein cholesterol to low
      density lipoprotein ratio (HDL-C/LDL-C) and triglyceride to high density
      lipoprotein cholesterol ratio (TG/HDL-C) were identified according to the
      Harmonization (H_MS) criterion. RESULTS: The predominant anthropometric marker
      that significantly influence metabolic risk factors among the pre- and
      postmenopausal women was waist-to-hip ratio (premenopausal: p- 0.004, 0.026 and
      0.002 for systolic blood pressure (SBP), fasting blood glucose (FBG) and HDL-C;
      postmenopausal: p-0.012, 0.048, 0.007 and 0.0061 for diastolic blood pressure
      (DBP), FBG, triglyceride (TG) and high density lipoprotein cholesterol (HDL-C)
      respectively). Using the receiver operating characteristic (ROC) analysis, the
      area under the curve for WC, WHR, TG/HDL-C and HDL-C/TC among postmenopausal
      women were estimated at 0.6, 0.6, 0.8 and 0.8 respectively. The appropriate cut
      off values for WC, WHR, TG/HDL-C and HDL-C/TC that predicted the presence of
      metabolic syndrome were 80.5 cm, 0.84, 0.61 and 0.34 respectively. CONCLUSION:
      The presence of metabolic syndrome among Ghanaian postmenopausal women can be
      predicted using WC, WHR, TG/HDL-C and HDL-C/TC.

PMID- 22883106
TI  - Comparison of conventional and 3-dimensional computed tomography against
      histopathologic examination in determining pancreatic adenocarcinoma tumor size:
      implications for radiation therapy planning.
AB  - BACKGROUND AND PURPOSE: This study seeks to: (a) quantify radiologic-pathologic
      discrepancy for pancreatic adenocarcinoma by comparing tumor size on conventional
      computed tomography (C-CT) and 3-dimensional CT (3D-CT) to corresponding
      pathologic specimens; and (b) to identify clinico-pathologic characteristics
      predictive of radiologic-pathologic discrepancy to assist radiotherapy planning.
      MATERIALS AND METHODS: Sixty-three patients with pancreatic adenocarcinoma and
      preoperative C-CT and volume-rendered 3D-CT imaging within 6 weeks of resection
      were identified. Maximum tumor diameter (MTD) was measured on pathology, C-CT,
      and 3D-CT and compared for each patient as well as among different clinico
      pathologic subgroups. RESULTS: There was a trend toward C-CT underestimation of
      MTD compared to final pathology (p=0.08), but no significant difference between
      3D-CT MTD and pathology (p=0.54). Pathologic tumor size was significantly
      underestimated by C-CT in patients with larger pathologic tumor size (>3.0 cm,
      p=0.0001), smaller tumor size on C-CT (<3.0 cm, p=0.003), higher CA19-9 (>90
      U/mL, p=0.008), and location in the pancreatic head (p=0.015). A model for
      predicting pathologic MTD using C-CT MTD and CA19-9 level was generated.
      CONCLUSIONS: 3D-CT may allow for more accurate contouring of pancreatic tumors
      than C-CT. Patients with the above clinico-pathologic characteristics may require
      expanded margins relative to tumor size estimates on C-CT during radiotherapy
      planning.

PMID- 22883107
TI  - Dosimetric explanations of fatigue in head and neck radiotherapy: an analysis
      from the PARSPORT Phase III trial.
AB  - BACKGROUND: An unexpected finding from the phase III parotid sparing radiotherapy
      trial, PARSPORT (ISRCTN48243537, CRUK/03/005), was a statistically significant
      increase in acute fatigue for those patients who were treated with intensity
      modulated radiotherapy (IMRT) compared to standard conventional radiotherapy
      (CRT). One possible explanation was the difference in dose to central nervous
      system (CNS) structures due to differing beam portals. Using data from the trial,
      a dosimetric analysis of individual CNS structures was performed. METHOD:
      Dosimetric and toxicity data were available for 67 patients (27 CRT, 40 IMRT).
      Retrospective delineation of the posterior fossa, brainstem, cerebellum,
      pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia was
      performed. Dosimetry was reviewed using summary statistics and dose-volume
      atlases. RESULTS: A statistically significant increase in maximum and mean doses
      to each structure was observed for patients who received IMRT compared to those
      who received CRT. Both maximum and mean doses were significantly higher for the
      posterior fossa, brainstem and cerebellum for the 42 patients who reported acute
      fatigue of Grade 2 or higher (p <= 0.01) compared to the 25 who did not. Dose
      volume atlases of the same structures indicated that regions representing larger
      volumes and higher doses to each structure were consistent with a higher
      incidence of acute fatigue. There was no association between the dose
      distribution and acute fatigue for the other structures tested. CONCLUSIONS: The
      excess fatigue reported in the IMRT arm of the trial may, at least in part, be
      attributed to the dose distribution to the posterior fossa, cerebellum and
      brainstem. Future studies that modify dose delivery to these structures may allow
      us to test the hypothesis that radiation-induced fatigue is avoidable.

PMID- 22883108
TI  - GhWRKY15, a member of the WRKY transcription factor family identified from cotton
      (Gossypium hirsutum L.), is involved in disease resistance and plant development.
AB  - BACKGROUND: As a large family of regulatory proteins, WRKY transcription factors
      play essential roles in the processes of adaptation to diverse environmental
      stresses and plant growth and development. Although several studies have
      investigated the role of WRKY transcription factors during these processes, the
      mechanisms underlying the function of WRKY members need to be further explored,
      and research focusing on the WRKY family in cotton crops is extremely limited.
      RESULTS: In the present study, a gene encoding a putative WRKY family member,
      GhWRKY15, was isolated from cotton. GhWRKY15 is present as a single copy gene,
      and a transient expression analysis indicated that GhWRKY15 was localised to the
      nucleus. Additionally, a group of cis-acting elements associated with the
      response to environmental stress and plant growth and development were detected
      in the promoter. Consistently, northern blot analysis showed that GhWRKY15
      expression was significantly induced in cotton seedlings following fungal
      infection or treatment with salicylic acid, methyl jasmonate or methyl viologen.
      Furthermore, GhWRKY15-overexpressing tobacco exhibited more resistance to viral
      and fungal infections compared with wild-type tobacco. The GhWRKY15
      overexpressing tobacco also exhibited increased RNA expression of several
      pathogen-related genes, NONEXPRESSOR OF PR1, and two genes that encode enzymes
      involved in ET biosynthesis. Importantly, increased activity of the antioxidant
      enzymes POD and APX during infection and enhanced expression of NtAPX1 and NtGPX
      in transgenic tobacco following methyl viologen treatment were observed.
      Moreover, GhWRKY15 transcription was greater in the roots and stems compared with
      the expression in the cotyledon of cotton, and the stems of transgenic plants
      displayed faster elongation at the earlier shooting stages compared with wide
      type tobacco. Additionally, exposure to abiotic stresses, including cold,
      wounding and drought, resulted in the accumulation of GhWRKY15 transcripts.
      CONCLUSION: Overall, our data suggest that overexpression of GhWRKY15 may
      contribute to the alteration of defence resistance to both viral and fungal
      infections, probably through regulating the ROS system via multiple signalling
      pathways in tobacco. It is intriguing that GhWRKY15 overexpression in tobacco
      affects plant growth and development, especially stem elongation. This finding
      suggests that the role of the WRKY proteins in disease resistance may be closely
      related to their function in regulating plant growth and development.

PMID- 22883109
TI  - Effect of limited nickel availability on methane emission from EDTA treated
      soils: coenzyme M an alternative biomarker for methanogens.
AB  - Methanogens utilize simple carbon compounds to produce methane (CH(4)) under
      strictly anaerobic condition. During methanogenesis, methyl coenzyme M (MeCoM) is
      reduced by MeCoM reductase enzyme to CH(4) involving a nickel-containing cofactor
      F(430). In this experiment, strong chelating agent like
      ethylenediaminetetraacetic acid (EDTA) was applied in soil to study its
      feasibility for suppressing methanogen activity and CH(4) production in soil.
      Application of EDTA significantly (P<=0.05) reduced CH(4) production in soil.
      Application of 60 ppm EDTA (soil weight basis) was the most effective among all
      treatments. Applied EDTA forms complex compounds with heavy metals like nickel
      (Ni) and increases Ni concentration in soil solution. Since methanogenesis is
      intracellular process, it is necessary for methanogens to assimilate those Ni
      EDTA complexes inside cell to utilize Ni in EDTA treated soils. Results indicated
      that methanogens cannot utilize Ni in the presence of EDTA and that significantly
      (P<=0.05) reduced mcrA gene (coding MeCoM reductase enzyme) copy number and Co-M
      concentration in soil. Due to high correlation (r=0.901(*)) between Co-M
      concentration and mcrA gene copy numbers, Co-M concentration could be used as an
      alternative biomarker for methanogens. Therefore, it could be propose that 60 ppm
      EDTA could be an optimum dose to suppress CH(4) emission from soil by restricting
      Ni availability to methanogens.

PMID- 22883110
TI  - Pathway of diethyl phthalate photolysis in sea-water determined by gas
      chromatography-mass spectrometry and compound-specific isotope analysis.
AB  - The degradation mechanism of diethyl phthalate (DEP) in natural seawater under UV
      irradiation was investigated using a combination of intermediates detection and
      determination of stable carbon isotopic fractionation. Typical intermediates
      identified with gas chromatography-mass spectrometry (GC-MS) were mono-ethyl
      phthalate (MEP) and phthalic anhydride. Stable carbon isotope signature was
      determined by gas chromatography coupled with isotope ratio mass spectrometry
      through a combustion interface (GC-C-IRMS). A profound (13)C enrichment, with a
      delta(13)C isotope shift of 12.3+/-0.30/00 (f=0.09) in residual DEP molecule, was
      clearly an indicator to its photolysis. The reactive position isotope enrichment
      factor (epsilon(reactive position)) and apparent kinetic isotope effects (AKIE)
      were -35.25+/-2.260/00 and 1.075, respectively, indicating that the initial
      reaction step was cleavage of a CO bond in DEP photolysis. Based on these
      observations, a degradation pathway was proposed. First, a CO bond in DEP
      molecule was broken to form MEP. Then, MEP was further degraded to phthalic
      anhydride. Our work demonstrates that compound-specific isotope analysis (CSIA),
      when combined with intermediates analysis, is a reliable measure to deduce the
      mechanism of DEP photolysis. This approach might be extended as a reference for
      mechanism investigation in complicated environment systems.

PMID- 22883112
TI  - [Retrospect and prospect of endocrine therapy for hormone receptor positive
      advanced breast cancer patients].

PMID- 22883111
TI  - Melanosome-iron interactions within retinal pigment epithelium-derived cells.
AB  - Melanosomes were recently shown to protect ARPE-19 cells, a human retinal pigment
      epithelium (RPE) cell line, against oxidative stress induced by hydrogen
      peroxide. One postulated mechanism of antioxidant action of melanin is its
      ability to bind metal ions. The aim here was to determine whether melanosomes are
      competent to bind iron within living cells, exhibiting a property previously
      shown only in model systems. The outcomes indicate retention of prebound iron and
      accumulation of iron by granules after iron delivery to cells via the culture
      medium, as determined by both colorimetric and electron spin resonance analyses
      for bound-to-melanosome iron. Manipulation of iron content did not affect the
      pigment's ability to protect cells against H(2) O(2) , but the function of
      pigment granules within RPE cells should be extended beyond a role in light
      irradiation to include participation in iron homeostasis.

PMID- 22883113
TI  - [Clinical features and prognostic analysis in prostate cancer patients under 59
      years of age: a report of 72 cases].
AB  - OBJECTIVE: To explore the clinicopathological characteristics and prognostic
      factors in prostate cancer patients under 59 years of age. METHODS: From January
      2000 to October 2011, 566 prostate cancer patients underwent treatments. Among
      them, 72 (12.7%) patients under 59 years of age with the integrated clinical data
      were reviewed. The median follow-up period was 25 months (range: 1 - 108) and the
      median age 55 years (range: 16 - 59). Four (5.5%) cases had the clinical stage of
      II, 12 (16.7%) cases of stage III and 56 (77.8%) cases of stage IV. Progression
      free survival (PFS), overall survival (OS) and prognostic factors were analyzed.
      RESULTS: The rate of adenocarcinoma was 86.1% (62/72) and the Gleason score of 8
      10 69.1% (29/42). Special type carcinoma accounted for 13.9% (10/72). The median
      time to androgen-independent prostate cancer (AIPC) was 12 months after endocrine
      therapy. The 1-, 3- and 5-year PFS were 53.8%, 12.1% and 6.1% and those for OS
      85.2%, 58.8% and 15.6% respectively. The prognostic factors were age, baseline
      prostate special antigen (PSA), types of pathology, tumor stage and local
      treatment by univariate analysis. The type of pathology was an independent
      prognostic factor of affecting significantly the prognosis by multivariate
      analysis. CONCLUSION: Prostate cancer patients under 59 years of age are
      characterized by misdiagnosis, complexity of pathology and high malignancy.
      Comprehensive regiment with predominant local therapy is an effective approach.

PMID- 22883114
TI  - [Wilson's disease in decision-making functions of Iowa gambling task].
AB  - OBJECTIVE: To explore the presence of impaired decision-making functions of
      Wilson's disease patients in Iowa gambling task (IGT) and its association with
      basal ganglia damage. METHODS: Thirty-two IGT patients with WD (WD group) and 29
      healthy people (control group) were recruited from the same period. And two
      options of high and low rewards were selected. Before the start of experiment, a
      basal figure of 2000 yuan was shown on computer display and they were prompted to
      win more money as much as possible. The general trend was observed with or
      without social learning effects. RESULTS: With the increased number of cards
      selected, the number of favorable and unfavorable selections shifted from
      negative to positive and gradually rose in the control group. However, such a
      pattern was absent in the WD group. The WD patients in the IGT group in Trial4
      and Trial5 were significantly lower than the controls (P = 0.009 and P = 0.020).
      CONCLUSION: The WD IGT patients have significant impairments of policy-making
      functions due to the damage of basal ganglia. And the effects of copper
      metabolism on cerebral cortex should be further studied in WD patients.

PMID- 22883115
TI  - [Diffusion tensor imaging analyses of white matter at an early stage of first
      episode schizophrenia].
AB  - OBJECTIVE: To explore the roles of diffusion tensor imaging (DTI) of white matter
      at an early stage of schizophrenia. METHODS: The participants were 20 first
      episode, medication-naive schizophrenics at an early stage (1 - 6 months) and 20
      healthy controls adjusted in gender and age during December 2009 and October
      2010. They underwent diffusion weighted magnetic resonance imaging with a single
      shot echo planar imaging (EPI) sequence aligned to straight axial plane. The
      fractional anisotropy (FA) images of two groups underwent two-sample paired t
      test with SPM5 software. RESULTS: The schizophrenics at an early stage
      demonstrated a significant decrease of regional white matter FA values in right
      anterior cingulated (MNI: x = 12, y = 24, z = -10; cluster = 145) and right
      middle occipital lobe (MNI: x = 36, y = -76, z = -2; cluster = 135). CONCLUSION:
      The altered white matter DTI in right anterior cingulated and middle occipital
      lobe may contribute to an early detection of schizophrenia.

PMID- 22883116
TI  - [Ridge regression analysis of pulmonary infection rate after transthoracic
      esophagectomy for esophageal cancer].
AB  - OBJECTIVE: To identify the influencing factors of pulmonary infections after
      transthoracic esophagectomy for esophageal cancer. METHODS: A retrospective
      review of 349 patients undergoing transthoracic esophagectomy at our hospital for
      esophageal cancer was performed between January and December 2009. The
      postoperative pneumonia rate was examined and 26 perioperative factors possibly
      affecting the postoperative respiratory complications were collected. Ridge
      regression modeling was performed to determine if a significant association
      existed between perioperative factors and postoperative pneumonia. RESULTS: The
      postoperative pneumonia rate of all patients was 27.8%. Eight perioperative
      factors were found to have affected significantly the postoperative respiratory
      complications. The influencing factors included (according to contribution):
      patient control epidural analgesia (PCEA), diabetes, general anesthesia plus
      epidural analgesia, other postoperative complications, one lung ventilation
      (OLV), transfusion volume of red blood cells (RBC), body mass index (BMI) and
      age. CONCLUSION: The major influencing factors of pulmonary infection after
      transthoracic esophagectomy for esophageal cancer are PCEA, diabetes, general
      anesthesia plus epidural analgesia, other postoperative complications, OLV,
      transfusion volume of RBC, BMI and age.

PMID- 22883117
TI  - [Main clinical features and prognosis of AIDS patients with the predominance of
      thrombocytopenia].
AB  - OBJECTIVE: To summarize the major clinical features, treatment, follow-up and
      outcomes of acquired immune deficiency syndrome (AIDS) patients with prominent
      thrombocytopenia. METHODS: The manifestations, signs, anti-virus regimens, CD4
      cell count, platelet count, prognosis and outcomes of 10 AIDS patients with
      prominent thrombocytopenia were collected and analyzed. RESULTS: After the
      administration of highly active antiretroviral therapy, platelet count and CD4
      significantly improved during a follow-up period up to 12 months. No
      opportunistic infections and HIV-related deaths occurred. CONCLUSION: The
      HIV/AIDS patients with prominent thrombocytopenia should start highly active
      antiretroviral therapy so as to effectively improve the prognosis and outcome.

PMID- 22883118
TI  - [Analysis of the misdiagnosis of bilateral iridocorneal endothelial syndrome].
AB  - OBJECTIVE: To analyze the misdiagnosis of bilateral iridocorneal endothelial
      (ICE) syndrome and the possible reasons. METHODS: The patients seen from January
      1998 to December 2011 at Beijing Tongren Hospital, misdiagnosed as bilateral ICE
      syndrome, were analyzed retrospectively. And a literature search was performed
      with a Wanfang computerized database website for the case studies of bilateral
      ICE syndrome. The history, clinical profiles and the findings of corneal, iris
      and anterior chamber examinations were analyzed. The clinical manifestations of
      patients with ICE syndrome were also compared with those of Axenfeld-Rieger
      syndrome, posterior polymorphous dystrophy (PPMD) and chronic iritis for
      differential diagnosis. RESULTS: Ten patients were diagnosed as bilateral ICE
      syndrome. However, among them, 5 patients were diagnosed as Axenfeld-Rieger
      syndrome, 2 patients as PPMD, 3 as chronic iritis and none as bilateral ICE
      syndrome. There were 9 Chinese reports of bilateral ICE syndrome in a total of 18
      patients. Analysis showed that Axenfeld-Rieger syndrome needed to be ruled out in
      10 patients, PPMD could not be ruled out in 2 patients while diagnosis could not
      be made in 6 patients for a lack of proof. CONCLUSION: Despite the reporting of
      bilateral cases, ICE syndrome is usually unilateral. With specific micrographic
      features for a definite diagnosis of ICE syndrome, ICE cells may become an
      important feature differentiating from Axenfeld-Rieger syndrome, PPMD and chronic
      iritis.

PMID- 22883119
TI  - [Analysis of risk factors of postoperative hemodialysis in patients undergoing
      off-pump coronary artery bypass grafting].
AB  - OBJECTIVE: To investigate the risk factors of postoperative hemodialysis in
      patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS:
      The perioperative data of 2379 consecutive patients undergoing OPCAB from
      November 2007 to February 2009 were analyzed retrospectively. Patients were
      divided into dialysis group and non-dialysis group according to their use of
      hemodialysis therapy or not. RESULTS: Fifty-four patients experienced
      hemodialysis postoperatively. The incidence of hemodialysis was 2.3%, the
      mortality rate of dialysis group and non-dialysis group was 18.5% and 0.9%
      respectively. Univariate analysis showed that these factors significantly related
      with the postoperative dialysis:intraoperative ventricular fibrillation, emergent
      cardiopulmonary bypass, preoperative atrial fibrillation, intraoperative atrial
      fibrillation, preoperative renal dysfunction, intraoperative high-dose adrenaline
      usage, ventricular aneurysm, combined valvular disease, hypertension, age and
      numbers of grafting vessels. Multivariate logistic regression showed that
      intraoperative ventricular fibrillation, intraoperative high-dose adrenaline
      usage, hypertension, age and the numbers of grafting vessel were the risk factors
      of postoperative hemodialysis for patients undergoing OPCAB surgery. CONCLUSION:
      Intraoperative ventricular fibrillation, intraoperative high-dose adrenaline
      usage, hypertension, age and the numbers of grafting vessels were the independent
      predictors of postoperative hemodialysis in patients undergoing OPCAB surgery.

PMID- 22883120
TI  - [Outcomes of anterior versus posterior instrumentation under different surgical
      procedures in the treatment of thoracolumbar spinal tuberculosis in adults].
AB  - OBJECTIVE: To compare the outcomes of anterior verus posterior instrumentation
      under different surgical procedures in the surgical management of thoracolumbar
      spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 241
      adult patients with thoracolumbar spinal TB underwent radical debridement and
      strut grafting plus anterior or posterior instrumentation in single-stage or two
      stages. The mean age was 39 years (range: 16 - 67). The mean follow-up period for
      189 patients was 37 months (range: 22 - 72). Among them, 157 cases underwent > 3
      weeks of chemotherapeutic regimen of isoniazid, rifampin, pyrazinamide and
      ethambutol and the remaining 32 were operated for neurological impairment after 6
      18 h with the same chemotherapeutic regimen. Except for 8 patients with skip
      lesions undergoing hybrid anteroposterior instrumentation, anterior
      instrumentation was utilized in 74 patients (Group A) and posterior
      instrumentation in 107 patients (Group B). RESULTS: In both groups, local
      symptoms of all patients were relieved significantly 1-3 weeks postoperatively.
      And 10/14 cases (71%) in Group A and 14/19 cases (74%) in Group B with
      neurological deficits had excellent or good clinical outcomes (P > 0.05). The
      levels of erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.4
      mm/h preoperatively to normal at 8-12 weeks postoperatively. Kyphosis degrees
      were corrected by a mean of 11.5 degrees  in Group A and 12.6 degrees  in Group B
      (P < 0.01). The correction loss was 6.8 degrees  in Group A and 6.1 degrees  in
      Group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were
      92.5% and 91.8% respectively at the final follow-up (P > 0.05). Severe
      complications did not occur. CONCLUSION: Either anterior or posterior
      instrumentation can obtain good results in correction and maintenance of
      deformity, clearance of foci, decompression of spinal cord and pain relief in the
      treatment of thoracolumbar spinal TB as long as the surgical indications are
      properly selected. Posterior instrumentation may be superior to anterior
      instrumentation in the correction and maintenance of deformity.

PMID- 22883121
TI  - [Clinical significance of serum squamous cell carcinoma antigen in the diagnosis,
      treatment and prognosis of cervical squamous cell carcinoma].
AB  - OBJECTIVE: To explore the clinical significance of squamous cell carcinoma
      antigen (SCC-Ag) in the diagnosis, treatment and prognosis of cervical squamous
      cell carcinoma. METHODS: The serum SCC-Ag concentrations were measured for 1195
      patients with cervical squamous cell carcinoma, 54 patients with non-squamous
      cell type cervical cancer, 325 patients with cervical intraepithelial neoplasm
      and 69 healthy women treated at Gynecology Ward of Shengjing Hospital, China
      Medical University from August 2008 to October 2010. And the correlations with
      their clinical pathological features of squamous cell carcinoma were analyzed and
      the changes in the diagnosis, treatment and prognosis monitored. RESULTS: Serum
      SCC-Ag in patients with cervical squamous cell carcinoma showed a sensitivity of
      62.32% and a specificity of 90.10% with the optimal cutoff point of diagnosis at
      1.45 ug/L. The differences of pretreatment serum SCC-Ag levels were statistically
      significant in clinical stage, histological differentiation, depth of invasion
      and lymph node metastasis (P < 0.01). The posttreatment serum SCC-Ag levels of
      106 patients undergoing radical surgery and 264 patients on chemotherapy
      significantly decreased and were significant different with their pretreatment
      levels (P < 0.05). There was no relationship of serum SCC-Ag levels and human
      papillomavirus (HPV) opportunistic infection (all P > 0.05). The best threshold
      values of pretreatment serum SCC-Ag concentration for predicting early
      postoperative cervical lymph node metastasis and prognosis of cervical cancer
      were 2.15 and 12.1 ug/L respectively. CONCLUSION: As a relatively specific tumor
      maker for cervical squamous cell carcinoma, squamous cell carcinoma antigen is
      correlated with clinicopathological features of cervical squamous cell carcinoma.
      And it has important clinical reference values in the diagnosis, prognosis,
      follow-up evaluation and treatment monitoring of cervical squamous cell
      carcinoma.

PMID- 22883122
TI  - [Efficacy and safety of insulin aspart versus regular human insulin for women
      with gestational diabetes mellitus].
AB  - OBJECTIVE: To explore the efficacy and safety of human aspart versus regular
      human insulin in women with gestational diabetes mellitus (GDM). METHODS: A total
      of 80 women with GDM during pregnancy delivered at our hospital divided into 2
      groups: Group 1 with human aspart and regular human insulin N while Group 2 with
      regular human insulin R and N. The levels of glucose were compared before and
      after 2 h at breakfast, lunch and supper at Day 1, 3 and 5. And the outcomes of
      women and their babies were evaluated. RESULTS: No significant difference in
      general characteristics existed between two groups. Except for breakfast of Day
      3, no significant difference was found in terms of the amount of insulin, the
      time of satisfactory glucose level and delivery time point, etc. There was no
      significant inter-group difference in the outcomes of pregnant women and their
      babies. CONCLUSION: The efficacy and safety of human aspart or regular human
      insulin are comparable for the women with gestational diabetes mellitus.

PMID- 22883123
TI  - [Surgical treatment of neuroendoscopy with supported channel for hypertensive
      intraventricular hemorrhage].
AB  - OBJECTIVE: To evaluate the value and efficacy of surgical treatment with
      neuroendoscopy with supported channel for hypertensive intraventricular
      hemorrhage (HIVH). METHODS: The clinical data of 32 patients with hypertensive
      intraventricular hemorrhage were retrospectively analyzed. And they underwent
      neuroendoscopy with supported channel. RESULTS: Computed tomography scans at Day
      1 postoperation revealed that the evacuation of intraventricular hematoma was
      85.4% in all patients. The Glasgow coma score (GCS) at Week 1 postoperation was
      significantly higher than that at preoperation. The postoperative outcomes were
      intracranial infection (n = 1), mortality (n = 1) and secondary hemorrhage (n =
      3). All patients were followed up for 3 months. According to Glasgow outcome
      scale (GOS), there were excellent recovery (n = 17), moderate disability (n = 7),
      severe disability (n = 5) and vegetative survival (n = 3). CONCLUSION: The
      surgical treatment of neuroendoscopy with supported channel for HIVH offers great
      advantages with a low rate of complications and favorable outcomes.

PMID- 22883124
TI  - [Spiral computed tomography imaging of internal carotid artery diameter: a report
      of 260 cases].
AB  - OBJECTIVE: To explore the diameter of internal carotid artery by arterial phase
      imaging of multi-slice spiral computed tomography (CT). METHODS: A total of 260
      routine brain CT scans of the examiner were performed. And the arterial phase
      images of carotid artery were acquired, observed and measured through a three
      dimensional reconstruction workstation. On the diameters of target sections were
      measured on the multiplanar reconstruction (MPR) images of carotid artery. Two
      groups were categorized according to gender and 3 groups by age (25 - 40 yr, 41 -
      60 yr and 61 - 85 yr) for statistical analysis. RESULTS: The diameter data of
      internal carotid artery had statistical significances among genders and 3 age
      groups (P < 0.05). CONCLUSION: The diameter of internal carotid artery may be
      evaluated by the arterial phase imaging of multi-slice spiral CT so that the
      reference data can be provided for clinical diagnosis.

PMID- 22883125
TI  - [Management of acute massive pulmonary thrombosis embolism with interventional
      techniques].
AB  - OBJECTIVE: To assess the efficacy and safety of interventional techniques in the
      treatment of deep venous thrombosis (DVT) and its complication of acute massive
      pulmonary thrombosis embolism (PTE). METHODS: Twenty massive PTE patients
      received the examinations of Doppler ultrasonography, computed tomography (CT)
      and venography. After a definite diagnosis, interventional therapy was used for
      symptomatic controls. The interventional procedures included catheter
      fragmentation and suction (n = 11), catheter-directed thrombolysis (n = 7), stent
      placement (n = 4) and inferior vena cava (IVC) filter placement (n = 11). After
      the above procedures, low doses of urokinase and heparin were prescribed for 1
      week. During a follow-up period of 6 - 24 months, the findings of CT, radiography
      and ultrasound were re-examined. RESULTS: Interventions were successful. The
      success rates of fragmentation and suction and iliac vein stenting were both
      100%. No major complications occurred. Pulmonary embolism involved main trunks
      and branches of lungs. Both arterial blood pressure and oxygen saturation were
      below normal values. After interventions, the clinical symptoms and angiographic
      results improved obviously. CONCLUSION: It is safe and effective to apply
      catheter-directed mechanical fragmentation, suction and thrombolysis in the
      treatment of DVT and PTE. IVC filter may be useful for the prevention of PTE.

PMID- 22883126
TI  - [Analysis of misdiagnosed cases with benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To analyze the misdiagnosed cases with benign paroxysmal positional
      vertigo (BPPV). METHODS: During October 2010 to January 2011, a total of 287
      patients with dizziness visited the Dizziness Clinic at Changzheng Hospital,
      Second Military Medical University. Forty-eight misdiagnosed cases with BPPV were
      collected and their clinical data were analyzed. All 48 cases were diagnosed by
      the Dix-Hallpike or Roll test maneuver. RESULTS: (1) CLINICAL FEATURES: there
      were 38 females and 10 males with an average age of 54 +/- 12 years old (range:
      31 - 87). Posterior semicircular canal was involved in 75.0% (36/48) whereas the
      horizontal semicircular and multiple canals in 20.8% (10/48) and 4.2% (2/48)
      respectively. All patients were treated successfully. And 41 cases (85.4%) were
      cured on the first visiting day. Recurrences of BPPV occurred in 6 cases during
      the follow-up. (2) The initial visiting departments consisted of the department
      of general internal medicine 43.8% (21/48), department of neurology 27.1%
      (13/48), department of osteology 18.7% (9/48), ear, nose & throat (ENT)
      department 2.1% (1/48) and other departments 8.3% (4/48). In addition, 68.7%
      (33/48) of them frequented the general out-patient clinics during their initial
      visits and the other 31.3% (15/48) used the emergency services. (3) The initial
      diagnoses included vertebrobasilar insufficiency/cerebral circulation
      insufficiency 27.1% (13/48), cervical spondylosis 27.1% (13/48), cerebral
      infarction 4.2% (2/48), Meniere's disease 2.1% (1/48) and others 10.4% (5/48);
      Besides, 29.1% (14/48) of them had no diagnosis. (4) The average clinic visits
      per patient were 3.4 times (164 visits/48 cases). (5) The most commonly performed
      tests included brain computed tomography (CT) (28 person-times), cervical
      magnetic resonance imaging (MRI) (19 person-times), brain MRI (18 person-times),
      cervical radiography (18 person-times) and cervical CT (8 person-times).
      CONCLUSION: In these misdiagnosed cases of BPPV, most of them were middle-aged
      women. They were most likely to have their first consultations in the departments
      of general internal medicine and neurology. Therefore these two departments
      should pay more attention to applying the maneuver of Dix-Hallpike or Roll test
      so as to reduce the misdiagnosis of BPPV and the waste of healthcare resources.

PMID- 22883127
TI  - [Treatment of greater trochanter fracture after total hip replacement].
AB  - OBJECTIVE: To explore the treatment of greater trochanter fracture after total
      hip replacement (THR). METHODS: This series consisted of 3 males and 8 females
      with fractures of greater trochanter after total or partial hip replacement from
      2004 to 2009. The mean age at the time of fracture diagnosis was 69 years old
      (range: 52 - 79). Two fractures were seen on radiograph at Day 2 postoperation
      and 3 found during a regular follow-up within the first 7 months after primary
      THR. They had no symptoms. Six patients fell and five of them occurred over 2
      years after THR. The average migration between trochanter and proximal femur were
      12 mm (range: 3 - 38). Ten cases underwent protected weight bearing for 6 - 12
      weeks and avoidance of active abduction until union was complete or there was no
      pain. Only one case suffered hip dislocation with a 38-mm migration and underwent
      operative repair of greater trochanter with suture. Hip pain, instability, range
      of motion and Trendlenburg gait were examined during a regular follow-up.
      Evaluations of fracture migration and bone healing were performed from the
      radiograph of AP and lateral views of hip. RESULTS: There was no patient loss.
      The mean follow-up period was 40 months (range: 12 - 68). All had nearly normal
      function and no symptoms at the latest follow-up. For 10 non-operatively treated
      cases, the fractures remained non-displaced and the Trendlenburg sign was
      negative at the final visit. Bone healing occurred in 5 patients. Fibrous union
      occurred in another 6 patients. CONCLUSION: The post-THR fractures of greater
      trochanter are usually stable and may be treated non-operatively.

PMID- 22883128
TI  - [Effects of activating and inhibiting Wnt/beta-catenin signaling pathway on
      murine model of eutopic endometrium and endometriosis].
AB  - OBJECTIVE: To employ the classical Wnt/beta-catenin signaling pathway
      interference to explore the effects on the functional changes of eutopic
      endometrium stromal cells and the differences between endometriosis in a murine
      model. METHODS: Two out of three mouse groups received an injection of either
      Wnt/beta-catenin signaling pathway activator or blocker. Later the endometrial
      tissue samples were obtained to develop endometrial stromal cell cultures for the
      detection of cell invasion ability via Boyden chamber invasion assay and Western
      blot (WB). Then the methods of WB and Immunohistochemical staining (IHC) were
      used to examine the factors of eutopic endometrium. And an endometriosis model
      was established to investigate the factors of signaling pathway via quantitative
      polymerase chain reaction (QPCR) and IHC. RESULTS: According to WB test, the
      level of beta-catenin, GSK-3beta and APC in the activation group were
      significantly higher than in the inhibition group (P < 0.01). In Boyden chamber
      invasion assay, the number of cells on membranes in the trial group was
      significantly higher than the control group [(113 +/- 12) vs (64 +/- 13)]. The
      expressions of VEGF and MMP-9 in the endometrial stromal cells culture from
      Boyden chamber assay analyzed via WB were ranked from highest to lowest
      respectively as activation group (vs control group was 35.6% and 27.4% higher),
      control group and inhibition group (vs control group was 12.3% and 30.4% lower).
      Furthermore, the endometrial E-cadherin and VEGF examined via IHC respectively
      showed a positive expression in inhibitor group and strong positive expression in
      activation group. QPCR showed the level of Wnt3, Wnt7, GSK3beta, Lef and E
      cadherin in the activation group was higher than those in the inhibition group (P
      < 0.05). CONCLUSION: The intervention of WNT signaling pathway in vivo cause the
      changes of eutopic endometrial invasion and adhesion function, and further affect
      the development of endometriosis. Wnt/beta-catenin signaling pathway may promote
      the eutopic endometrial cell proliferation and improve the ability of eutopic
      endometrial implantation, invasion, metastasis and angiogenesis.

PMID- 22883129
TI  - [Effects of injectable chitosan/beta-glycerol phosphate disodium/collagen
      scaffold on the growth and differentiation of myoblasts].
AB  - OBJECTIVE: To prepare injectable chitosan/beta-glycerol phosphate
      disodium/collagen scaffold and observe its effects upon the growth and
      differentiation of myoblasts. METHODS: After the preparations, 2 wt% chitosan (C)
      solution, 50 wt% beta-glycerol phosphate disodium (GP) solution and 2 mg/ml
      collagen (Co) solution were mixed on ice according to a volume ratio of 5:1:6 to
      yield a thermosensitive injectable scaffold. To assess the cytotoxicity of
      scaffold, the extraction fluids of different concentrations were added into the
      myoblast culture. Then relative growth rate (RGR) was calculated. The growth and
      differentiation state of myoblasts in routine culture or gel-coated plates were
      compared. Myoblasts were encapsulated in C/GP/Co solution before gelation to
      perform a 3-dimensional culture and then observed dynamically. RESULTS: No
      cytotoxicity was demonstrated. No significant difference of proliferation index
      was demonstrated (P > 0.05) but fusion index and size of myotube increased
      significantly (P < 0.05). Thriving viability and proliferation were verified by
      the observations of laser confocal scanning microscope and scanning electron
      microscope. CONCLUSION: C/GP/Co scaffold is a promising carrier for the culture
      and transplantation of myoblasts.

PMID- 22883130
TI  - Development of a sham comparator for thoracic spinal manipulative therapy for use
      with shoulder disorders.
AB  - Prior studies indicate thoracic spinal manipulative therapy (SMT) improves
      shoulder pain and disability. However, these studies are limited by no control or
      sham-treatment group. A valid sham comparator for thoracic SMT is needed.
      Subjects (n=69) without shoulder pain were randomized to one of three groups:
      thoracic SMT, sham-SMT, or sham-ultrasound; and told they were randomized to
      manual therapy, range of motion, or ultrasound respectively. Perceived effects of
      the treatment on shoulder motion, pain, and functional were questioned before and
      after treatment. Believability was assessed by asking if the subject believed
      they received the active or inactive intervention. Shoulder active range of
      motion (AROM) was measured with a digital inclinometer before and after treatment
      by a blinded examiner. Believability of treatment was not significantly different
      between the SMT and sham-SMT (p=0.12), but a greater proportion (p=0.03) believed
      they received the active treatment in the SMT group (78.3%) as compared to the
      sham-ultrasound (47.8%). No differences in perception of treatment effects
      between the treatment groups were detected (p>=0.1). Shoulder internal rotation
      AROM increased in the thoracic SMT group (mean difference=3.7 degrees ; p=0.006),
      but did not change within the sham-SMT (p=0.44) or sham-ultrasound (p=0.18)
      groups. Shoulder flexion did not change within any group. These preliminary
      results indicate the sham-SMT is an adequate sham comparator for SMT with similar
      expectations and believability as SMT active treatment. The sham-SMT had an inert
      effect on shoulder AROM. Sham-ultrasound was not believable as an active
      treatment. Future studies need to validate these results in patients with
      shoulder pain.

PMID- 22883131
TI  - Epidemiological surveillance linked to an outreach psychological support program
      after the Xynthia storm in Charente-Maritime, France, 2010.
AB  - INTRODUCTION: Following the Xynthia storm of February 2010 in France, an outreach
      program was initiated by the regional health authorities during the post
      emergency phase to improve access to mental health care for the population
      exposed to the floods. The program was designed to complement routine health and
      social care services. It relied on a special telephone service and outreach
      consultations located in the town halls of the five most affected cities. The
      objective of this outreach service was to provide initial psychological
      counseling free of charge and without appointment. Another objective was to refer
      persons for appropriate treatment and follow-up by routine health care services.
      A surveillance program was developed to monitor the use of mental health services
      by first-time users, describe outreach service users with psychological
      manifestations, and provide timely information to decision makers. METHODS:
      Health providers working in affected towns were asked to complete an individual
      record sheet for each person who displayed psychological manifestations directly
      or indirectly linked with the storm on their first visit, and to send it to the
      regional health office. Participation was voluntary. Data analysis was performed
      monthly during the six-month surveillance period. RESULTS: Only mental health
      providers participated in the surveillance. A total of 227 individual files were
      sent from April 7 through September 19, 2010. New cases were mainly female
      adults, and one fifth had a past history of psychiatric illness. Depressive signs
      and anxiety were the most commonly reported symptoms, followed by signs of post
      traumatic stress disorder. A total of five feedback reports were produced for
      surveillance participants (informants) and authorities. CONCLUSION: With
      initiation in the post-emergency phase of a disaster and timely regular feedback,
      the surveillance program enabled the authors to describe the occurrence of
      psychological distress, monitor mental health service use by first-time users,
      and provide guidance to health authorities. This research showed the advantages
      of integrating epidemiology in the development of strategy for mental health and
      psychosocial support in the aftermath of natural catastrophes.

PMID- 22883132
TI  - Fluorescence diagnosis of bladder cancer: a novel in vivo approach using 5
      aminolevulinic acid (ALA) dendrimers.
AB  - What's known on the subject? and What does the study add? Fluorescence cystoscopy
      with hexylaminolevulinate (h-ALA, Hexvix(r)) is known to improve tumour detection
      in non-muscle-invasive bladder cancer. However, specificity is relatively low and
      the intensity of the observed fluorescence signal decreases over time due to
      protoporphyrin IX (PpIX) efflux. This study evaluates in an in vivo model the use
      of a dendritic 5-aminolevulinic acid compound for fluorescence diagnosis.
      Fluorescence ratios between tumour and urothelium as well as muscle were
      significantly better as compared with h-ALA. Sustained synthesis of PpIX accounts
      for preservation of fluorescence for >24 h. OBJECTIVE: * To overcome the relative
      lack of tumour selectivity of fluorescence-guided cystoscopy using 5
      aminolevulinic acid (ALA) or its ester derivative (e.g. hexylaminolevulinate, h
      ALA; Hexvix(r)), we evaluated the use of dendrimers bearing different ALA loads
      in rats bearing orthotopic bladder tumours. MATERIALS AND METHODS: * Rat bladders
      were instilled with h-ALA or ALA dendrimers and fluorescence ratio between tumour
      and normal urothelium, as well as tumour and muscle and depth of fluorescence
      were determined with Image J software. * Quantification of ALA and/or esters
      systemic reabsorption was evaluated by high-performance liquid chromatography.
      RESULTS: * Slow hydrolysis of ALA from dendrimers as observed in vitro implies a
      higher initial ALA load and longer resting times in vivo. Sustained synthesis of
      protoporphyrin IX (PpIX) explains persistence of fluorescence for >24 h. * There
      were significantly better fluorescence ratios with dendrimers, as well as higher
      penetration depths and absence of systemic reabsorption. CONCLUSION: * The
      prolonged and sustained PpIX synthesis, the improved tumour selectivity with a
      deeper penetration and the absence of systemic reabsorption are primary
      indicators that ALA dendrimers could be an alternative to h-ALA in fluorescence
      guided cystoscopy.

PMID- 22883133
TI  - Exertional fatigue in patients with CKD.
AB  - BACKGROUND: Fatigue is one of the most prevalent symptoms in chronic kidney
      disease (CKD). However, fatigue mechanisms are poorly understood due in part to
      nonspecific definitions. This study investigates exertional fatigue during
      simulated activities of daily living, focusing on oxygen delivery and
      utilization. STUDY DESIGN: "Explanatory" matched-cohort study. PARTICIPANTS &
      SETTING: 13 patients with CKD (stages 3b-4; mean age, 62 +/- 13 [SD] years) and
      13 healthy controls, mean matched for age, height, body mass and composition, and
      physical activity level. Participants completed an incremental cycle ergometer
      test to simulate energy expenditure of typical activities of daily living.
      FACTOR: 4 exercise intensities: 1, 1.8, 2.4, and 3.1 metabolic equivalent tasks
      (METs). OUTCOMES: The primary outcome was exertional fatigue by rating of
      perceived exertion (RPE) on a 6-20 scale. MEASUREMENTS: Other multidimensional
      measures of fatigue: UK Short Form Health Survey 36 (UK SF-36) Vitality and
      Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
      subscales. Physiologic measures of the oxygen transport and utilization chain
      (expired gas analysis, cardiac output, and arterial oxygen content) and blood
      lactate. RESULTS: RPE was increased in patients compared with controls at 2.4
      (10.5 [ie, light] +/- 2.7 vs 8.7 [very light] +/- 1.7 units) and 3.1 (12.5
      [somewhat hard] +/- 2.6 vs 10.2 [light] +/- 1.7 units) METs (interaction P =
      0.03), which was consistent with higher chronic fatigue in patients by both the
      UK SF-36 Vitality (P = 0.01) and FACIT-Fatigue (P = 0.004) subscales. Arterial
      oxygen content was decreased in patients (P = 0.001), but cardiac output and
      oxygen extraction ratio were unchanged, decreasing oxygen delivery (P = 0.04).
      Respiratory exchange ratio (P = 0.004) and blood lactate production (P = 0.002)
      were increased. LIMITATIONS: Those inherent to a matched-cohort study.
      CONCLUSIONS: Using a novel application of the outcome measure RPE, patients with
      non-dialysis-dependent CKD reported considerable exertional fatigue during
      simulated activities of daily living. Poor compensation for mild anemia
      contributed to this symptom. In addition to anemia, the entire oxygen transport
      chain needs to be targeted to treat fatigue in patients with CKD.

PMID- 22883134
TI  - Fibroblast growth factor 23, high-sensitivity cardiac troponin, and left
      ventricular hypertrophy in CKD.
AB  - BACKGROUND: Detectable levels of cardiac troponins are common in individuals with
      chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular
      disease. Abnormal cardiac troponin values are associated with coronary artery
      disease and left ventricular hypertrophy (LVH) and predict poor clinical
      outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to
      LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high
      sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T)
      levels in CKD and examined the role of LVH in this association. STUDY DESIGN:
      Cross-sectional observational study. SETTING & PARTICIPANTS: 153 stable
      outpatients with non-dialysis-dependent CKD. PREDICTOR: The primary predictor was
      FGF-23 level. OUTCOMES: hs-cTnI, hs-cTnT. MEASUREMENTS: FGF-23, hs-cTnI, hs-cTnT;
      left ventricular mass index (LVMI) assessed by echocardiography; coronary artery
      calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated
      as potential mediators of the effect of FGF-23 on hs-cTnI/T. RESULTS: Mean age
      was 64 +/- 12 (SD) years, mean estimated glomerular filtration rate was 34 +/- 11
      mL/min/1.73 m(2), median FGF-23 level was 120 (25th-75th percentile, 79-223)
      reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5
      14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9)
      pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a
      healthy population in 42% and 61% of patients, respectively. In unadjusted and
      multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly
      with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of
      FGF-23 and hs-cTnI/T levels. LIMITATIONS: Vitamin D levels were not measured. The
      prevalence of coronary artery disease may have been underestimated because it was
      ascertained by self-report. CONCLUSIONS: Minimally elevated cTnI and cTnT levels,
      detectable by high-sensitivity assays, are associated with elevated FGF-23 levels
      in stable outpatients with CKD. FGF-23-associated LVH may contribute to
      detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD.

PMID- 22883135
TI  - Associations between coronary calcification on chest radiographs and mortality in
      hemodialysis patients.
AB  - BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) guidelines
      recommend lateral abdominal radiographs to assess vascular calcification in
      incident dialysis patients. However, nearly all dialysis patients in the United
      States receive chest radiographs at dialysis therapy inception, which may provide
      readily available information on coronary artery (CAC) and aortic arch
      calcification (AAC). We determined the prevalence of CAC and AAC visible on plain
      chest radiographs and their associations with mortality in our dialysis
      population. STUDY DESIGN: Retrospective analysis. SETTING & PARTICIPANTS: 93
      participants who received maintenance hemodialysis at the San Diego Veterans
      Affairs Medical Center in 2009-2010. PREDICTOR: Presence of CAC and AAC as
      evaluated by a radiologist. OUTCOME: All-cause mortality. RESULTS: Average age
      was 64 years, 22% were African American, and 97% were men. CAC and AAC
      prevalences were 25% and 58%, respectively. During 20 months' follow-up, 28%
      died. CAC was associated with mortality in models including cardiovascular (HR,
      2.41; 95% CI, 1.04-5.59) and dialysis-related (HR, 2.86; 95% CI, 1.24-6.60) risk
      factors. AAC was associated with HRs of 5.25 (95% CI, 1.46-17.72) in
      cardiovascular risk factor-adjusted models and 7.31 (95% CI, 2.03-26.34) in
      dialysis models. When CAC and AAC were both included in models, both CAC (HR,
      3.40; 95% CI, 1.24-9.36) and AAC (HR, 6.23; 95% CI, 1.64-23.66) remained
      significantly associated with mortality. LIMITATIONS: The study sample is
      relatively small and mostly male. CONCLUSIONS: CAC and AAC are highly prevalent
      on chest radiographs in dialysis patients and strongly associated with mortality
      independent of one another. Because these images are nearly ubiquitous,
      inexpensive, and often obtained for other indications, they should be considered
      for risk assessment in hemodialysis patients. Future studies are required to
      determine whether CAC or AAC on chest radiography is additive or duplicative of
      the risk of aorto-iliac calcification on lateral abdominal radiographs currently
      suggested by KDIGO.

PMID- 22883136
TI  - Protocol: High-throughput and quantitative assays of auxin and auxin precursors
      from minute tissue samples.
AB  - BACKGROUND: The plant hormone auxin, indole-3-acetic acid (IAA), plays important
      roles in plant growth and development. The signaling response to IAA is largely
      dependent on the local concentration of IAA, and this concentration is regulated
      by multiple mechanisms in plants. Therefore, the precise quantification of local
      IAA concentration provides insights into the regulation of IAA and its biological
      roles. Meanwhile, pathways and genes involved in IAA biosynthesis are not fully
      understood, so it is necessary to analyze the production of IAA at the metabolite
      level for unbiased studies of IAA biosynthesis. RESULTS: We have developed high
      throughput methods to quantify plant endogenous IAA and its biosynthetic
      precursors including indole, tryptophan, indole-3-pyruvic acid (IPyA), and indole
      3-butyric acid (IBA). The protocol starts with homogenizing plant tissues with
      stable-labeled internal standards added, followed by analyte purification using
      solid phase extraction (SPE) tips and analyte derivatization. The derivatized
      analytes are finally analyzed by selected reaction monitoring on a gas
      chromatograph-mass spectrometer (GC-MS/MS) to determine the precise abundance of
      analytes. The amount of plant tissue required for the assay is small (typically 2
      10 mg fresh weight), and the use of SPE tips is simple and convenient, which
      allows preparation of large sets of samples within reasonable time periods.
      CONCLUSIONS: The SPE tips and GC-MS/MS based method enables high-throughput and
      accurate quantification of IAA and its biosynthetic precursors from minute plant
      tissue samples. The protocol can be used for measurement of these endogenous
      compounds using isotope dilution, and it can also be applied to analyze IAA
      biosynthesis and biosynthetic pathways using stable isotope labeling. The method
      will potentially advance knowledge of the role and regulation of IAA.

PMID- 22883137
TI  - CASE plots for the chemotype-based activity and selectivity analysis: a CASE
      study of cyclooxygenase inhibitors.
AB  - Structure-activity characterization of molecular databases plays a central role
      in drug discovery. However, the characterization of large databases containing
      structurally diverse molecules with several end-points represents a major
      challenge. For this purpose, the use of chemoinformatic methods plays an
      important role to elucidate structure-activity relationships. Herein, a general
      methodology, namely Chemotype Activity and Selectivity Enrichment plots, is
      presented. Chemotype Activity and Selectivity Enrichment plots provide graphical
      information concerning the activity and selectivity patterns of particular
      chemotypes contained in structurally diverse databases. As a case study, we
      analyzed a set of 658 compounds screened against cyclooxygenase-1 and
      cyclooxygenase-2. Chemotype Activity and Selectivity Enrichment plots analysis
      highlighted chemotypes enriched with active and selective molecules against
      cyclooxygenase-2; all this in a simple 2D graphical representation. Additionally,
      the most active and selective chemotypes detected in Chemotype Activity and
      Selectivity Enrichment plots were analyzed separately using the previously
      reported dual activity-difference maps. These findings indicate that Chemotype
      Activity and Selectivity Enrichment plots and dual activity-difference maps are
      complementary chemoinformatic tools to explore the structure-activity
      relationships of structurally diverse databases screened against two biological
      end-points.

PMID- 22883139
TI  - Psycho-social outcome in liver transplanted children: beware of emotional self
      assessment!
AB  - BACKGROUND: Psycho-social outcome in children after liver transplantation (LT) is
      known to be inferior to age-related peers. Yet, when children and their parents
      are questioned by their nurse or physician about the child's psycho-social well
      being, the answers usually are very positive. We hypothesized that patients and
      their parents after LT report their psycho-social well-being too enthusiastically
      when enquired by their personal care takers. METHODS:  INCLUSION CRITERIA: LT at
      the Children's University Hospital of Geneva 1992-2007, age >3 years, <16 years,
      time after LT >2 years. Children and their parents were questioned by their well
      known, familiar nurse at the annual follow up visit about their personal well
      being. To allow for evaluation of answers, scores (good, medium, bad) were
      attributed to the different questions. 46 children were included in the study.
      RESULTS: Mean age at enquiry was 9.7 years (SD 4 years), mean time after LT was
      7.5 years (SD 4.2 years). The different themes were reported as good for: parent
      child relationship (83%), relationship with peers (98%), relation with siblings
      (39%), sport activities (54%), play activities (78%), school performance (87%),
      expression skills (67%), and general behavior (89%). CONCLUSION: Most of our LT
      children and their parents consider, during a personal interview with a closely
      related, familiar nurse, that the child's psycho-social outcome is good. Yet, it
      is generally acknowledged that children after LT have negatively altered psycho
      social outcomes. Thus, emotionally influenced reports about psycho-social outcome
      in children after LT must be looked at with care.

PMID- 22883138
TI  - Causes and determinants of inequity in maternal and child health in Vietnam.
AB  - BACKGROUND: Inequities in health are a major challenge for health care planners
      and policymakers globally. In Vietnam, rapid societal development presents a
      considerable risk for disadvantaged populations to be left behind. The aim of
      this review is to map the known causes and determinants of inequity in maternal
      and child health in Vietnam in order to promote policy action. METHODS: A review
      was performed through systematic searches of Pubmed and Proquest and manual
      searches of "grey literature." A thematic content analysis guided by the
      conceptual framework suggested by the Commission on Social Determinants of Health
      was performed. RESULTS: More than thirty different causes and determinants of
      inequity in maternal and child health were identified. Some determinants worth
      highlighting were the influence of informal fees and the many testimonies of
      discrimination and negative attitudes from health staff towards women in general
      and ethnic minorities in particular. Research gaps were identified, such as a
      lack of studies investigating the influence of education on health care
      utilization, informal costs of care, and how psychosocial factors mediate
      inequity. CONCLUSIONS: The evidence of corruption and discrimination as mediators
      of health inequity in Vietnam calls for attention and indicates a need for more
      structural interventions such as better governance and anti-discriminatory laws.
      More research is needed in order to fully understand the pathways of inequities
      in health in Vietnam and suggest areas for intervention for policy action to
      reach disadvantaged populations.

PMID- 22883140
TI  - Testing reliability and validity of Lorensen's Self-care Capability Scale (LSCS)
      among older home-living, care-dependent individuals in Norway.
AB  - AIM AND OBJECTIVE: The aim of this study was to test reliability and validity of
      the Lorensen's Self-Care Capability Scale (LSCS). BACKGROUND: The assessment of
      self-care capability among older people living at home is essential for
      maintaining independence for as long as possible. METHOD: The study sample
      consisted of 242 home nursing patients who were 75 + years old and living at
      home. The responsible home nurses documented their answers. In addition to the
      LSCS, help dependency, subjective health and demographic characteristics were
      recorded. Various statistical analyses were used to assess reliability and
      validity of the LSCS. RESULTS: Reliability of the LSCS was supported by a
      Cronbach's alpha coefficient of 0.97. Regarding validity, six factors extracted
      in the factor analysis explained 69.8% of the variance in the group. The
      extracted factors supported the underlying theoretical assumptions of the
      instrument. Construct validity was supported by significant differences between
      groups with expected low and expected high LSCS scores, respectively. Concurrent
      validity was established by a significant correlation between LSCS and Barthel's
      ADL Index. CONCLUSION AND IMPLICATIONS FOR PRACTICE: This study has shown that
      LSCS is a reliable and valid instrument for assessing self-care capability in
      older people living at home.

PMID- 22883141
TI  - Phasing of many thousands of genotyped samples.
AB  - Haplotypes are an important resource for a large number of applications in human
      genetics, but computationally inferred haplotypes are subject to switch errors
      that decrease their utility. The accuracy of computationally inferred haplotypes
      increases with sample size, and although ever larger genotypic data sets are
      being generated, the fact that existing methods require substantial computational
      resources limits their applicability to data sets containing tens or hundreds of
      thousands of samples. Here, we present HAPI-UR (haplotype inference for unrelated
      samples), an algorithm that is designed to handle unrelated and/or trio and duo
      family data, that has accuracy comparable to or greater than existing methods,
      and that is computationally efficient and can be applied to 100,000 samples or
      more. We use HAPI-UR to phase a data set with 58,207 samples and show that it
      achieves practical runtime and that switch errors decrease with sample size even
      with the use of samples from multiple ethnicities. Using a data set with 16,353
      samples, we compare HAPI-UR to Beagle, MaCH, IMPUTE2, and SHAPEIT and show that
      HAPI-UR runs 18* faster than all methods and has a lower switch-error rate than
      do other methods except for Beagle; with the use of consensus phasing, running
      HAPI-UR three times gives a slightly lower switch-error rate than Beagle does and
      is more than six times faster. We demonstrate results similar to those from
      Beagle on another data set with a higher marker density. Lastly, we show that
      HAPI-UR has better runtime scaling properties than does Beagle so that for larger
      data sets, HAPI-UR will be practical and will have an even larger runtime
      advantage. HAPI-UR is available online (see Web Resources).

PMID- 22883142
TI  - A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of
      positive selection in Papua New Guinea.
AB  - Signals of archaic admixture have been identified through comparisons of the
      draft Neanderthal and Denisova genomes with those of living humans. Studies of
      individual loci contributing to these genome-wide average signals are required
      for characterization of the introgression process and investigation of whether
      archaic variants conferred an adaptive advantage to the ancestors of contemporary
      human populations. However, no definitive case of adaptive introgression has yet
      been described. Here we provide a DNA sequence analysis of the innate immune gene
      STAT2 and show that a haplotype carried by many Eurasians (but not sub-Saharan
      Africans) has a sequence that closely matches that of the Neanderthal STAT2. This
      haplotype, referred to as N, was discovered through a resequencing survey of the
      entire coding region of STAT2 in a global sample of 90 individuals. Analyses of
      publicly available complete genome sequence data show that haplotype N shares a
      recent common ancestor with the Neanderthal sequence (~80 thousand years ago) and
      is found throughout Eurasia at an average frequency of ~5%. Interestingly, N is
      found in Melanesian populations at ~10-fold higher frequency (~54%) than in
      Eurasian populations. A neutrality test that controls for demography rejects the
      hypothesis that a variant of N rose to high frequency in Melanesia by genetic
      drift alone. Although we are not able to pinpoint the precise target of positive
      selection, we identify nonsynonymous mutations in ERBB3, ESYT1, and STAT2-all of
      which are part of the same 250 kb introgressive haplotype-as good candidates.

PMID- 22883143
TI  - Genomic patterns of homozygosity in worldwide human populations.
AB  - Genome-wide patterns of homozygosity runs and their variation across individuals
      provide a valuable and often untapped resource for studying human genetic
      diversity and evolutionary history. Using genotype data at 577,489 autosomal
      SNPs, we employed a likelihood-based approach to identify runs of homozygosity
      (ROH) in 1,839 individuals representing 64 worldwide populations, classifying
      them by length into three classes-short, intermediate, and long-with a model
      based clustering algorithm. For each class, the number and total length of ROH
      per individual show considerable variation across individuals and populations.
      The total lengths of short and intermediate ROH per individual increase with the
      distance of a population from East Africa, in agreement with similar patterns
      previously observed for locus-wise homozygosity and linkage disequilibrium. By
      contrast, total lengths of long ROH show large interindividual variations that
      probably reflect recent inbreeding patterns, with higher values occurring more
      often in populations with known high frequencies of consanguineous unions. Across
      the genome, distributions of ROH are not uniform, and they have distinctive
      continental patterns. ROH frequencies across the genome are correlated with local
      genomic variables such as recombination rate, as well as with signals of recent
      positive selection. In addition, long ROH are more frequent in genomic regions
      harboring genes associated with autosomal-dominant diseases than in regions not
      implicated in Mendelian diseases. These results provide insight into the way in
      which homozygosity patterns are produced, and they generate baseline homozygosity
      patterns that can be used to aid homozygosity mapping of genes associated with
      recessive diseases.

PMID- 22883144
TI  - The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with
      proximal dominant involvement.
AB  - Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN
      P) is an autosomal-dominant neurodegenerative disorder characterized by
      widespread fasciculations, proximal-predominant muscle weakness, and atrophy
      followed by distal sensory involvement. To date, large families affected by HMSN
      P have been reported from two different regions in Japan. Linkage and haplotype
      analyses of two previously reported families and two new families with the use of
      high-density SNP arrays further defined the minimum candidate region of 3.3 Mb in
      chromosomal region 3q12. Exome sequencing showed an identical c.854C>T
      (p.Pro285Leu) mutation in the TRK-fused gene (TFG) in the four families. Detailed
      haplotype analysis suggested two independent origins of the mutation.
      Pathological studies of an autopsied patient revealed TFG- and ubiquitin
      immunopositive cytoplasmic inclusions in the spinal and cortical motor neurons.
      Fragmentation of the Golgi apparatus, a frequent finding in amyotrophic lateral
      sclerosis, was also observed in the motor neurons with inclusion bodies.
      Moreover, TAR DNA-binding protein 43 kDa (TDP-43)-positive cytoplasmic inclusions
      were also demonstrated. In cultured cells expressing mutant TFG, cytoplasmic
      aggregation of TDP-43 was demonstrated. These findings indicate that formation of
      TFG-containing cytoplasmic inclusions and concomitant mislocalization of TDP-43
      underlie motor neuron degeneration in HMSN-P. Pathological overlap of
      proteinopathies involving TFG and TDP-43 highlights a new pathway leading to
      motor neuron degeneration.

PMID- 22883145
TI  - TCTN3 mutations cause Mohr-Majewski syndrome.
AB  - Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders
      characterized by abnormalities in the oral cavity, face, and digits and
      associated phenotypic abnormalities that lead to the delineation of 13 OFDS
      subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary
      sequencing, we identified truncating TCTN3 mutations as the cause of an extreme
      form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and
      brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals
      with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly
      syndromes) led us to identify four additional truncating TCTN3 mutations in
      unrelated fetal cases with overlapping Meckel and OFD IV syndromes and one
      homozygous missense mutation in a family with Joubert syndrome. By exploring
      roles of TCTN3 in human ciliary related functions, we found that TCTN3 is
      necessary for transduction of the sonic hedgehog (SHH) signaling pathway, as
      revealed by abnormal processing of GLI3 in patient cells. These results are
      consistent with the suggested role of its murine ortholog, which forms a complex
      at the ciliary transition zone with TCTN1 and TCTN2, both of which are also
      implicated in the transduction of SHH signaling. Overall, our data show the
      involvement of the transition zone protein TCTN3 in the regulation of the key SHH
      signaling pathway and that its disruption causes a severe form of ciliopathy,
      combining features of Meckel and OFD IV syndromes.

PMID- 22883146
TI  - A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of
      lung cancer.
AB  - Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) may
      promote cancer development and progression by inducing tumorigenesis and drug
      resistance. To assess whether the copy-number variation g.CNV-30450 located in
      the MAPKAPK2 promoter has any effect on lung cancer risk or prognosis, we
      investigated the association between g.CNV-30450 and cancer risk in three
      independent case-control studies of 2,332 individuals with lung cancer and 2,457
      controls and the effects of g.CNV-30450 on cancer prognosis in 1,137 individuals
      with lung cancer with survival data in southern and eastern Chinese populations.
      We found that those subjects who had four copies of g.CNV-30450 had an increased
      cancer risk (odds ratio = 1.94, 95% confidence interval [CI] = 1.61-2.35) and a
      worse prognosis for individuals with lung cancer (with a median survival time of
      only 9 months) (hazard ratio = 1.47, 95% CI = 1.22-1.78) compared with those with
      two or three copies (with a median survival time of 14 months). Meanwhile, four
      copies of g.CNV-30450 significantly increased MAPKAPK2 expression, both in vitro
      and in vivo, compared with two or three copies. Our study establishes a robust
      association between the functional g.CNV-30450 in MAPKAPK2 and risk as well as
      prognosis of lung cancer, and it presents this functional copy-number variation
      as a potential biomarker for susceptibility to and prognosis for lung cancer.

PMID- 22883147
TI  - RBPJ mutations identified in two families affected by Adams-Oliver syndrome.
AB  - Through exome resequencing, we identified two unique mutations in recombination
      signal binding protein for immunoglobulin kappa J (RBPJ) in two independent
      families affected by Adams-Oliver syndrome (AOS), a rare multiple-malformation
      disorder consisting primarily of aplasia cutis congenita of the vertex scalp and
      transverse terminal limb defects. These identified mutations link RBPJ, the
      primary transcriptional regulator for the Notch pathway, with AOS, a human
      genetic disorder. Functional assays confirmed impaired DNA binding of mutated
      RBPJ, placing it among other notch-pathway proteins altered in human genetic
      syndromes.

PMID- 22883148
TI  - UV index values and trends in Santiago, Chile (33.5 degrees S) based on ground
      and satellite data.
AB  - We report on the surface UV index (UVI) variations in Santiago (Chile) a city
      with high air pollution and complex surrounding topography. Ground-based UV
      measurements were continuously carried out between January 1995 and December
      2011, by using a multi-channel filter radiometer (PUV-510). Ground-based
      measurements and satellite-derived data retrieved from the Total Ozone Mapping
      Spectrometer (TOMS), the Ozone Monitoring Instrument (OMI), and the Scanning
      Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY), were
      compared. We found that satellite-derived UVI products largely overestimate
      surface UVI. Our ground-based UVI measurements were significantly lower than TOMS
      derived UVI data: (46.1+/-6.3)% (in the period 1997-2003), and OMI-derived UVI
      data: (47.0+/-6.3)% (in the period 2005-2007). Clear-sky SCIAMACHY-derived UVI
      were found to be also nearly systematically greater than ground-based UVI
      measurements in the period 2002-2011. An exceptionally long period of clear skies
      between December 2010 and January 2011 was used to test further satellite-derived
      UVI data; in the whole period, OMI and SCIAMACHY data were 53.1% and 38.3%
      greater than our ground-based measurements, respectively. These differences are
      presumably due to aerosol load associated with the local pollution and the
      complex topography surrounding Santiago. In addition, linear regression allowed
      us to estimate trends that we use for forecasting. Methodological details are
      provided below.

PMID- 22883149
TI  - Circadian parameters are altered in two strains of mice with transgenic
      modifications of estrogen receptor subtype 1.
AB  - There are sex differences in free-running rhythms, activity level and activity
      distribution that are attributed, in part, to the action of gonadal hormones. We
      tested the hypothesis that non-classical estrogenic signaling pathways at
      estrogen receptor subtype 1 (ESR1) modify the amplitude and phase of activity. We
      used ESR1 knock-out mice (ERKO) and non-classical estrogen receptor knock-in mice
      (NERKI). ERKO animals are unable to respond to estrogen at the ESR1 and NERKI
      animals lack the ability to respond to estrogens via the estrogen response
      element-mediated pathway, but can still respond via non-classical mechanisms. We
      compared intact male and female ERKO, NERKI and wildtype (WT) mice with respect
      to total wheel-running activity, activity distribution across the 24-h day, phase
      angle of activity onset and free-running period (tau) and the duration of
      activity in constant conditions. WT females had significantly greater activity
      than WT males, and this activity was more consolidated to the dark phase of the
      light:dark cycle. These sex differences were absent in the NERKI and ERKO
      animals. Among females, NERKI and ERKO animals had greater activity during the
      light phase than WT counterparts. Additionally, we have identified a novel
      contribution of non-classical estrogen signaling pathways on the distribution of
      activity. Our data suggest that total activity is ESR1-dependent and daily
      activity patterns depend on both classical and non-classical actions of
      estrogens. These data will aid in identifying the mechanisms underlying sex
      differences in sleep-wake cycles and the influence of steroid hormones on
      circadian patterns.

PMID- 22883154
TI  - ["English: the fifth age in the language of medicine"].

PMID- 22883155
TI  - [Colorectal surgery in patients over 65 years of age].
AB  - BACKGROUND: There is a limited functional reserve in patients over 65 years of
      age which is conducive to more frequent postoperative complications. Disease
      extension at the time of diagnosis (clinical stage) and complete tumor resection
      are two independent risk factors that have a direct influence on survival. AIMS:
      To describe the factors that influence morbidity and mortality in patients over
      65 years of age after colorectal surgery. MATERIAL AND METHODS: A retrospective,
      observational, descriptive study was carried out within the time frame of January
      2004 and December 2009 on 105 colon cancer patients after colorectal surgery.
      They were divided into two groups, one under 65 years of age and the other over
      65 years of age, in order to compare preoperative comorbidity, as well as
      morbidity and mortality 30 days after surgery. RESULTS: Of the 105 patient total
      (53,3%), 56 were <= 65 years of age. There were complications in 42,8% of the
      patients, and those of early and less severe presentation were the most frequent;
      late complications were more frequent in patients <= 65 vs > 65 years of age
      (16,0% vs 10,2%). Overweight (BMI > 25 kg/m(2)) was observed in 35,0% of the
      study population. Patients > 65 years of age had fewer comorbidities. The most
      common causes of reintervention were anastomosis dehiscence and postoperative
      hemorrhage. Mortality in the group was 6,6% and sepsis was the most frequent
      cause of death. CONCLUSIONS: Colorectal surgery in patients over 65 years of age
      has an acceptable complication frequency and a low mortality rate. Our results
      suggest that patients older than 65 years of age be treated with the same
      prospects for cure as younger patients.

PMID- 22883156
TI  - Geographic disparities in access to lung transplantation before and after
      implementation of the lung allocation score.
AB  - The 62 lung transplant centers in the United States are unevenly distributed. We
      examined whether remote dwelling (distance from one's primary residence to the
      nearest lung transplant center) or rural dwelling (as opposed to urban)
      influences patients' access to lung transplantation, and whether such
      relationships changed following introduction of the lung allocation score (LAS)
      in May 2005. Between July 2001 and February 2009, 14 015 patients were listed for
      lung transplantation and 7923 (56.5%) were transplanted. Americans lived a median
      of 90.3 miles (IQR: 45.3-159.4) from the closest transplant center. Distance from
      a lung transplant center was inversely associated with the hazard of being listed
      before LAS implementation (adjusted HR for 100 miles = 0.87 [0.83-0.90]) and
      afterward (0.81 [0.78-0.85]); LAS implementation did not modify this relationship
      (p = 0.38). Once waitlisted, distance from the closest center was not associated
      with time to transplantation, and among those transplanted, distance was not
      associated with survival. Similar results were identified for rural, as opposed
      to urban, residence. We conclude that geographic disparaties exist in access to
      lung transplantation in the United States. These are mediated by listing
      practices rather than by transplantation rates, and were not mitigated by LAS
      implementation.

PMID- 22883157
TI  - Preparation of a novel hyperbranched carbosilane-silica hybrid coating for trace
      amount detection by solid phase microextraction/gas chromatography.
AB  - Phenyl-ended hyperbranched carbosilane (HBC) is synthesized and immobilized onto
      the inner wall of a fused silica capillary column using a sol-gel process. The
      hybrid coating layer formed is used as a stationary phase for gas chromatography
      (GC) and as an adsorption medium for solid phase microextraction (SPME).
      Trifluoroacetic acid, as a catalyst in this process, helps produce a homogeneous
      hybrid coating layer. This result is beneficial for better column chromatographic
      performances, such as high efficiency and high resolution. Extraction tests using
      the novel hybrid layer show an extraordinarily large adsorption capacity and
      specific adsorption behavior for aromatic compounds. A 1 ppm trace level
      detectability is obtained with the SPME/GC work model when both of the stationary
      phase and adsorption layer bear a hyperbranched structure. A large amount of
      phenyl groups and a low viscosity of hyperbranched polymers contribute to these
      valuable properties, which are important to environment and safety control,
      wherein detection sensitivity and special adsorption behavior are usually
      required.

PMID- 22883158
TI  - Evaluation of comprehensive two-dimensional gas chromatography-time-of-flight
      mass spectrometry for the analysis of polycyclic aromatic hydrocarbons in
      sediments.
AB  - This study evaluates the feasibility of comprehensive two-dimensional gas
      chromatography coupled to time-of-flight mass spectrometry (GC * GC-ToF MS) for
      the determination of the 15+1 EU PAHs in sediments. Experimental variables
      affecting the injection, chromatographic separation and analytical detection of
      the analytes have systematically been optimised. Under finally proposed
      conditions, a satisfactory resolution among critical pairs/groups of PAHs,
      including benz[a]anthracene, cyclopenta[cd]pyrene and chrysene, the three
      benzofluoranthene isomers, indeno[1,2,3-cd]pyrene from dibenz[a,h]anthracene
      (DahA), and DahA from dibenz[a,c]anthracene, has been achieved using DB-5 * BPX
      50 as column combination with a run time of 1 h. The feasibility of the method
      for the analysis of real-life samples has been demonstrated by accurate
      determination of relevant target PAHs in the certified harbour sediment BCR-535
      (deviations among certified concentration values and those calculated using the
      proposed method lower than 3%); and by successful application to sediments
      sampled from a relevant protected area located in the South of Spain. The low
      methodological limits of detection (LODs) obtained for most of the targeted PAHs
      (in the 5.7-60 MUg/kg range, as calculated for real samples) guarantied accurate
      quantification of the target compounds at the low levels expected in these types
      of pristine matrices. The strong retention experienced by the heaviest
      dibenzopyrene isomers included in the study resulted in relatively high LODs for
      these analytes; nevertheless, these compounds were detected at concentration
      levels above the corresponding LOD in some of the analysed sediments. In
      addition, the enhanced identification power provided by GC * GC-ToF MS for the
      identification of non-target analytes allowed the tentative identification of a
      group of polynuclear aromatic thiophenes in some of the test samples. Finally,
      the potential of the use of normalised bubble plots for the fast screening of the
      potential PAH sources has been demonstrated.

PMID- 22883159
TI  - Reversal of elution order in a single second dimension by changing the first
      column nature in comprehensive two-dimensional gas chromatography.
AB  - This paper explains how one single stationary phase can involve two different
      elution orders for linear alkanes, cyclic alkanes, aromatics and phenols using
      comprehensive two-dimensional gas chromatography. For this purpose, a coal
      derived middle distillate was injected in nonpolar*semipolar and polar*semipolar
      configurations implying the same second dimension stationary phase
      (trifluoropropyl). Results show that even if the same column is utilised as a
      second dimension, the group-type elution order is reversed from one combination
      to the other. This can be explained as follows:for the polar*semipolar
      combination, each fraction eluting from the first dimension contains species that
      differ so much in terms of boiling points, that volatility plays a key role in
      the second isothermal separation. This is exemplified by the separation of a
      phenol and demonstrated using the proportional relationship between retention
      times, vapour pressures and activity coefficients. Moreover, van't Hoff plots
      (plots of ln k vs. 1/T) demonstrated the influence of the elution temperature
      from the first dimension on the second dimension separation. Therefore, available
      choice of stationary phase's combinations is much higher considering that one
      single column leads to very different retentions for similar compounds. Finally,
      this can explain why a reverse orthogonality approach is usually proficient for
      the separation of polar compounds.

PMID- 22883160
TI  - A practical interface designed for on-line polymer monolith microextraction:
      synthesis and application of poly(4-vinylpyridine-co-ethylene glycol
      dimethacrylate) monolith.
AB  - A simple and facile needle-adapter was designed for constructing manual on-line
      polymer monolith microextraction-high performance liquid chromatography (PMME
      HPLC). A capillary poly(4-vinylpyridine-co-ethylene glycol dimethacrylate)
      [poly(VP-co-EGDMA)] monolith was prepared by in situ polymerization, using 4
      vinylpyridine (VP) and ethylene glycol dimethacrylate (EGDMA) as functional
      monomer and cross-linker, respectively. The synthesized monolith was used as the
      extraction medium for concentrating four EPA priority pollutants, 2-chlorophenol,
      2,4-dichlorophenol, 2,4,6-trichlorophenol and pentachlorophenol, from water
      samples. The effect of the dosage of porogen polyethylene glycol 6000 (PEG) on
      back pressure and extraction performance of the capillary monolith was also
      investigated. Moreover, the influences of several parameters (such as extraction
      time, desorption time, content of MeOH in sample solution and sample pH) were
      examined to obtain the optimal PMME conditions. As a result, the established on
      line PMME-HPLC protocol, with good extraction efficiency (80.6-91.7%),
      satisfactory recovery (94.7-106% and 76.8-86.3% for water and serum samples,
      respectively) and low detection limit (0.3-1.4 MUg/L), exhibited potential
      applicability for the analysis of chlorophenols in environmental and biological
      samples.

PMID- 22883161
TI  - Capillary electrophoresis in classical and carrier ampholytes-based background
      electrolytes applied to separation and characterization of gonadotropin-releasing
      hormones.
AB  - Capillary zone electrophoresis (CZE) in classical buffer-based background
      electrolytes (BGEs) and carrier ampholytes-based capillary electrophoresis
      (CABCE) using narrow pH cuts of carrier ampholytes (CA) as constituents of quasi
      isoelectric BGEs have been applied to separation and characterization of
      synthetic human and salmon gonadotropin-releasing hormones (GnRH) and their
      derivatives and fragments. The selectivity, separation efficiency, resolution and
      speed of CZE and CABCE analyses have been compared within a wide pH range of the
      BGEs (3.50-9.75) using two mixtures of structurally related GnRH peptides as
      model analytes. A baseline separation of mixture 1 (human GnRH and its three
      fragments) was achieved in CA-based BGEs at pH 3.5 and in both classical and CA
      based BGEs within the pH range 7.00-9.75. Full separation of mixture 2 (salmon
      GnRH, its two fragments and human GnRH fragment) was obtained in both types of
      BGEs at acidic pH values 3.5 and 4.00 and at neutral pH 7.00. In addition to the
      separation of related GnRHs, their effective electrophoretic mobilities were
      determined and from the dependences of mobilities on pH, the isoelectric points
      (pI) of analyzed peptides were estimated. The pI values obtained by CABCE were in
      a good agreement with those determined by CZE in classical BGEs but in some cases
      rather different from those predicted by theoretical calculations.

PMID- 22883162
TI  - Preparation of organic-silica hybrid boronate affinity monolithic column for the
      specific capture and separation of cis-diol containing compounds.
AB  - A new boronate-silica hybrid monolithic column was prepared using a one-pot
      approach with 3-acrylamidophenylboronic acid (AAPBA) as the boronate affinity
      ligand. The AAPBA-silica monolith exhibited several attractive advantages. First,
      it is highly hydrophilic, providing excellent specificity and avoiding the
      presence of organic solvent in the mobile phase. Second, due to its large surface
      area, it exhibited a high binding capacity, 49.5 MUmol/mL, the highest among the
      boronate affinity monolithic columns appeared in the literature. Third, the
      monolith can bind with cis-diol containing compounds at pH as low as 6.5, which
      not only avoids the use of basic pH conditions at which the silica monolith may
      hydrolysis but also facilitates the applications to wider sample range. Finally,
      the hybrid monolithic column exhibited apparent secondary separation capability,
      which allows for two-dimensional (2D) separation of cis-diol compounds in a
      single column. Due to these merits, the AAPBA-silica hybrid monolithic column can
      be a promising separation medium for the analysis of cis-diol containing
      compounds.

PMID- 22883163
TI  - Factors associated with the epidemic of hospitalizations due to atrial
      fibrillation.
AB  - Recent reports have described that hospitalizations for atrial fibrillation (AF)
      are continuing to increase. Given that hospitalizations are responsible for most
      of the economic burden associated with AF, the aim of this study was to
      characterize the impact of age and how changing procedural practices may be
      contributing to the increasing rates of AF hospitalizations. The annual age- and
      gender-specific incidence of hospitalizations for AF, electrical cardioversions,
      electrophysiologic studies, and radiofrequency ablation procedures in Australia
      were determined from 1993 to 2007 inclusive. Over this 15-year follow-up period
      spanning almost 300 million person-years, a total of 473,501 hospitalizations for
      AF were identified. There was a relative increase in AF hospitalizations of 203%
      over the study period, in contrast to an increase for all hospitalizations of
      only 71%. Whereas the gender-specific incidence of hospitalizations remained
      stable, the age-specific incidence increased significantly over the study period,
      particularly in older age groups. AF hospitalizations associated with electrical
      cardioversions decreased from 27% to 14% over the study period.
      Electrophysiologic studies and radiofrequency ablation procedures contributed
      minimally to the overall increase in AF hospitalizations observed. In conclusion,
      in addition to the growing prevalence of AF because of the aging population,
      there is an increasing age-specific incidence of hospitalizations for AF,
      particularly in older age groups. In contrast, changing procedural trends have
      contributed minimally to the increasing number of AF-associated hospitalizations.
      Greater attention to older patients with AF is required to develop strategies to
      prevent hospitalizations and contain the growing burden on health care systems.

PMID- 22883164
TI  - Kidney function and progression of coronary artery calcium in community-dwelling
      older adults (from the Rancho Bernardo Study).
AB  - Longitudinal studies of the association of estimated glomerular filtration rate
      (eGFR) and albuminuria with coronary artery calcium (CAC), a measure of
      cardiovascular disease burden, are few and contradictory. In this study, 421
      community-dwelling men and women (mean age 67 years) without known heart disease
      had eGFRs assessed using the Modification of Diet in Renal Disease (MDRD)
      equation and albuminuria assessed by urine albumin/creatinine ratio (ACR) from
      1997 to 1999. The mean eGFR was 78 ml/min/1.73 m(2), and the median ACR was 10
      mg/g. CAC was measured using electron-beam computed tomography from 2000 to 2001,
      when the median total Agatston CAC score was 77; 4.5 years later, 338
      participants still without heart disease underwent repeat scans (median CAC score
      112); 46% of participants showed CAC progression, defined as an increase >=2.5
      mm(3) in square root-transformed CAC volume score. Cross-sectional and
      longitudinal logistic regression analyses showed no separate or joint association
      between eGFR or ACR and CAC severity or progression. In conclusion, this study
      does not support the use of eGFR or ACR to identify asymptomatic older adults who
      should be screened for subclinical cardiovascular disease with initial or
      sequential scanning for CAC. In the elderly, kidney function and CAC may not
      progress together.

PMID- 22883165
TI  - Frequency of asymptomatic disease among family members with noncompaction
      cardiomyopathy.
AB  - Noncompaction cardiomyopathy (NCC) is a primary cardiomyopathy characterized by
      an excessively prominent trabecular meshwork and deep intertrabecular recesses of
      the left ventricular walls. Most cases are inherited, with a dominant inheritance
      pattern. The aim of the present study was to determine the prevalence and
      clinical characteristics of cardiomyopathies in the close relatives of patients
      with NCC. We evaluated 156, mostly first-degree, family members of 44 adult
      patients with NCC who agreed to familial screening. A family history of cardiac
      disease was reported by 16 (36%) of the 44 patients, including premature sudden
      death in 8 families (18%). NCC (n = 32) or dilated cardiomyopathy (n = 9) was
      diagnosed in 41 relatives (26%) by echocardiography (n = 25), contrast
      echocardiography (n = 6), or magnetic resonance imaging (n = 10). Of these family
      members, 13 already had known cardiac symptoms and signs, but most (28 of 41)
      were asymptomatic. Most subjects with NCC had mild to moderate left ventricular
      dysfunction (n = 29, 71%). After a median follow-up of 55 months (interquartile
      range 43 to 93), most remained asymptomatic. Four family members were treated
      with prophylactic implantable cardioverter-defibrillator placement and 23 of
      those with NCC were treated with drugs, including angiotensin-converting enzyme
      inhibitors (41%), beta blockers (34%), and anticoagulants (17%). In conclusion,
      there is a high prevalence, mostly asymptomatic, of cardiac disease (26%) among
      first- and second-degree family members of patients with NCC. This warrants
      screening and offers an opportunity for early intervention.

PMID- 22883167
TI  - [Study on physique index set for Chinese children and adolescents].
AB  - OBJECTIVE: To provide data as age-gender dependent mean, standard deviation and
      percentile on height, weight, waist circumference (WC), hip circumference (HC),
      body mass index (BMI), waist hip ratio (WHR), waist to height ratio (WHtR) among
      7-16 year-olds Chinese children and adolescents, towards setting up diagnostic
      criteria on metabolic syndrome for them. METHODS: A representative sample
      involving 22,197 children and adolescence aged 7 to 16 years were randomly
      surveyed and they were from 6 representative geographical areas, including
      Beijing, Tianjin, Hangzhou, Shanghai, Chongqing and Nanning. A total of 21 858
      had available data, with male/female ratio as: 11,460/10,398. Using the standard
      methods, we measured height, weight, WC, HC, BMI, WHtR and other data in all age
      groups. Physique indexes among different geographic regions (North, Mid-west and
      East) were compared. RESULTS: (1) Both male and female showed an increasing trend
      of height, weight, waist circumference, hip circumference and BMI along with the
      increase of age. WHR of girls decreased gradually from 0.84 to 0.76 went from 7
      to 16 years old while WHR of boys changed from 0.87 to 0.81 accordingly. (2) WHtR
      was rarely affected by age. It fluctuated between 0.42-0.43 in all girls and 0.44
      0.45 in boys less than 11 years. WHtR of boys older than 12 years showed a slight
      decline from 0.45 to 0.42 of WHtR. (3) The average height, weight, BMI of
      children and adolescents from the northern regions (Beijing, Tianjin) were
      significantly higher than that of the mid-western (Chongqing, Nanning) and the
      eastern regions (Shanghai, Hangzhou) (P<0.001), while those from the mid-western
      region were slightly higher than that of the eastern region (P<0.05) in each of
      the age group. CONCLUSION: Reference values and percentile curves for WC and WHtR
      of Chinese children and adolescents were provided. For the assessment of central
      obesity. WHtR had the advantages of relative stability and small degree of
      variation and rarely affected by age and gender, when compared with WC, and could
      be used as an simple index to reflect the central obesity of children and
      adolescents.

PMID- 22883166
TI  - Brachial artery flow-mediated dilation following exercise with augmented
      oscillatory and retrograde shear rate.
AB  - BACKGROUND: Acute doses of elevated retrograde shear rate (SR) appear to be
      detrimental to endothelial function in resting humans. However, retrograde shear
      increases during moderate intensity exercise which also enhances post-exercise
      endothelial function. Since SR patterns differ with the modality of exercise, it
      is important to determine if augmented retrograde SR during exercise influences
      post-exercise endothelial function. This study tested the hypothesis that (1)
      increased doses of retrograde SR in the brachial artery during lower body supine
      cycle ergometer exercise would attenuate post-exercise flow-mediated dilation
      (FMD) in a dose-dependent manner, and (2) antioxidant vitamin C supplementation
      would prevent the attenuated post-exercise FMD response. METHODS: Twelve men
      participated in four randomized exercise sessions (90 W for 20 minutes) on
      separate days. During three of the sessions, one arm was subjected to increased
      oscillatory and retrograde SR using three different forearm cuff pressures (20,
      40, 60 mmHg) (contralateral arm served as the control) and subjects ingested
      placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure
      was performed with 1 g of vitamin C ingested prior to the session. RESULTS: Post
      exercise FMD following the placebo conditions were lower in the cuffed arm versus
      the control arm (arm main effect: P < 0.05) and without differences between cuff
      pressures (20 mmHg: 5.7 +/- 2.2%; 40 mmHg: 4.7 +/- 1.3%; 60 mmHg: 5.4 +/- 2.4%)
      (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and
      control arm increased from baseline (P < 0.05) but were not different (control:
      7.1 +/- 3.5% vs. cuffed: 6.6 +/- 3.3%) (P > 0.05). CONCLUSIONS: These results
      indicate that augmented oscillatory and retrograde SR in non-working limbs during
      lower body exercise attenuates post-exercise FMD without an evident dose-response
      in the range of cuff pressures evaluated. Vitamin C supplementation prevented the
      attenuation of FMD following exercise with augmented oscillatory and retrograde
      SR suggesting that oxidative stress contributes to the adverse effects of
      oscillatory and retrograde shear during exercise on FMD.

PMID- 22883168
TI  - [Association between both triglyceride level, newly identified carotid plaque and
      middle-aged and elderly population, Beijing].
AB  - OBJECTIVE: To evaluate the association between triglyceride (TG) level and newly
      identified 5-year carotid plaque and to explore the prediction value of TG level
      on the newly-identified carotid plaque with risk factors of traditional
      atherosclerosis. METHODS: A cohort study was adopted. The baseline survey
      including CVD risk factors and B-mode ultrasound of carotid artery was performed
      in 2002, and the second follow-up examination was performed in 2007. We evaluated
      1949 participants with lipid measurements and B-mode ultrasound of carotid
      arteries in the two surveys (with mean age as 57.9+/-8.1 years and 39.2% were
      men). The baseline TG levels were divided into four groups: group 1 (TG<1.13
      mmol/L), group 2 (TG=1.13-1.69 mmol/L), group 3 (TG=1.70-2.25 mmol/L) and group 4
      (TG>=2.26 mmol/L). Newly identified carotid plaque was regarded as the indicator
      of progression of carotid atherosclerosis. New relationship between fasting TG
      levels and newly identified carotid plaque was analysed. RESULTS: Compared to
      newly identified carotid plaque which including different TG level groups, the
      incidence of newly artery plaque had significantly increased along with the
      increase of baseline triglyceride level (30.8%, 38.8%, 41.9% and 44.2%
      respectively, with chi2=21.22, P<0.01). Compared to individuals (TG<1.13 mmol/L),
      TG seemed a risk factor of plaque progression (P<0.01). After adjusted for age,
      sex, dyslipidemia and other risk factors, high TG group (TG>=2.26 mmol/L)
      appeared a significant independent predictor of newly identified carotid plaque
      (OR=1.37, 95%CI: 1.00-1.86). When further stratifying the traditional
      atherosclerosis risk factors, we found that high TG group with smoking or
      hypertension was an independent factor of atherosclerosis progression.
      CONCLUSION: With the increase of triglyceride levels, the rate of newly
      identified carotid plaque also increased. After adjusting age, sex, dyslipidemia
      and other risk factors, serum fasting TG>=2.26 mmol/L appeared to be an
      independent predictor of newly developed carotid plaque.

PMID- 22883169
TI  - [Influence of central obesity on clustering of other risk variables on metabolic
      syndrome among adults with normal body mass index].
AB  - OBJECTIVE: To study the influence of central obesity on clustering of other
      metabolic syndrome (MS) risk variables among adults with normal body mass index.
      METHODS: Through cluster multistage and random sampling methods, local people
      aged>35 years old with normal body mass index (BMI=18.5-24.9 kg/m2) in Lanxi
      country were selected. Overnight fasting blood specimens of these people were
      collected. Chi-square test, analysis of covariance, and logistic regression
      analyses were performed. RESULTS: (1) 1821 residents were surveyed including 844
      male and 977 female subjects. The overall prevalence of MS was 8.68% and the
      overall prevalence of central obesity was 15.87%. Both prevalence rates of the
      two diseases appeared to be lower in males than in females (MS: 3.32% vs. 13.31%;
      center obesity: 5.57% vs. 24.77%, all P<0.001). (2) The overall positive rate of
      clustering on other MS risk variable was 36.02%, with 34.12% in males and 37.67%
      in females. Comparing the subjects who did not have central obesity, those
      subjects wth central obesity had higher positive rate in other MS risk variables.
      (3) Data from analysis of covariance showed that the level of waist circumference
      appeared an upward trend along with the count of other MS risk variables (all
      P<0.001). (4) Data from multivariable logistic regression analysis showed that
      central obesity was a risk factor on clustering of other MS risk variables.
      CONCLUSION: Control the level of waist circumference among normal body mass index
      was an effective method in preventing metabolic syndrome and cardiovascular
      disease in adults.

PMID- 22883170
TI  - [Assessment on the validity and reliability of Family Environment Scale on Motor
      Development for Urban Pre-school Children].
AB  - OBJECTIVE: To assess the validity and reliability of Family Environment Scale on
      Motor Development for Urban Pre-school Children (FESMDUPC) so as to provide valid
      and reliable tools for measuring the influencing factors from home environment on
      motor development of the children. METHODS: One thousand eight hundreds and
      twenty four preschool children from 15 kindergartens in Suzhou city were included
      in this study which related to reliability and validity of FESMDUPC. Data on test
      retest reliability, internal consistent reliability, content validity and
      construct validity were assessed using the Intra-class Correlation Coefficient
      (ICC), Cronbach alpha coefficient, Item-level content validity index (I-CVI) and
      Confirmatory Factor Analysis (CFA). When the Observation for Measurement of the
      Environment Revisited was used as criteria, the criteria-related validity of MABC
      was assessed, using the Spearman correlation analysis. RESULTS: This study showed
      that the ICC of all items was above or close to 0.9. The total Cronbach alpha
      coefficient was 0.875 and the Cronbach alpha coefficient was 0.868-0.873 when
      each item was deleted. Formal validity and reliability study showed that I-CVI of
      the 23 items was 0.79-1.00. The average I-CVI was 0.92. Results from the CFA
      model showed that chi2=1077.5, df=224 and chi2/df=4.810. Fit of Goodness on the
      other indices of the model were as follows: GFI (0.949), AGF (0.937), NFI
      (0.889), CFI (0.896), with each of them above or close to 0.9. The RMSEA was
      0.046 which showed that the model's Fit of Goodness could be accepted. The factor
      loadings were all above 0.3 with statistical significance. However, according to
      this model, the strengths of relationship between Outside Space, Inside Space and
      Toy were high, so the high-step CFA of FESMDUPC was further analyzed. The model's
      Fit of Goodness was good. The factor loadings were all above 0.3 with statistical
      significance. Results showed that the Spearman Coefficient of the total score of
      FESMDUPC and HOME scale was 0.476 (each P<0.001). Among them only the learning
      staff and movement variety were comparatively and highly correlated with Toy,
      Parental Rearing Patterns. Spearman coefficients were all above 0.3 (each
      P<0.001). CONCLUSION: The above results showed that the reliability of test
      retest, the internal consistent reliability, the content validity and the
      construct validity of FESMDUPC were fair and had met the basic psychometric
      demands. FESMDUPC could be used as a quantitative tool to assess the motor
      development among children.

PMID- 22883171
TI  - [Multi-state model in the evaluation of outcome on mild cognitive impairment to
      Alzheimer's disease].
AB  - OBJECTIVE: The aim of this study was to introduce the multi-state Markov model
      for the prediction of mild cognitive impairment (MCI) to Alzheimer's disease (AD)
      and to find out the related factors for AD prevention and early intervention
      among the elderly. METHODS: MCI, moderate to severe cognitive impairment, and AD
      were defined as state 1, 2 and 3, respectively. A three-state homogeneous model
      with discrete states and discrete times from data on six follow-up visits was
      constructed to explore factors for various progressive stages from MCI to AD.
      Transition probability and survival curve were made after the model fit
      assessment. RESULTS: At the level of 0.05, data from the multivariate analysis
      showed that gender (HR=1.23, 95%CI: 1.12-1.38), age (HR=1.37, 95%CI: 1.07-1.72),
      hypertension (HR=1.54, 95%CI: 1.31-2.19) were statistically significant for the
      transition from state 1 to state 2, while age (HR=0.78, 95%CI: 0.69-0.98),
      education level (HR=1.35, 95%CI: 1.09-1.86) and reading (HR=1.20, 95%CI: 1.01
      1.41) were statistically significant for transition from state 2 to state 1, and
      gender (HR=1.59, 95%CI: 1.33-1.89), age (HR=1.33, 95%CI: 1.02-1.64), hypertension
      (HR=1.22, 95%CI: 1.11-1.43), diabetes (HR=1.52, 95%CI: 1.12-2.00), ApoEe4
      (HR=1.44, 95%CI: 1.09-1.68) were statistically significant for transition from
      state 2 to state 3. Based on the fitted model, the three-year transition
      probabilities during each state at average covariate level were estimated.
      CONCLUSION: To delay the disease progression of MCI, phase by phase prevention
      measures could be adopted based on the main factors of each stage. Multi-state
      Markov model could imitate the natural history of disease and showed great
      advantage in dynamically evaluating the development of chronic diseases with
      multi-states and multi-factors.

PMID- 22883172
TI  - [Relationship between deliberate self-harm and suicidal behaviors in college
      students].
AB  - OBJECTIVE: To describe the prevalence of deliberate self-harm (DSH) and suicidal
      behaviors (SIB) as well as the relationship between them in a college student
      population. METHODS: A total of 4063 medical students were selected under the
      cluster sampling method in Anhui province. Data were analyzed by Pearson Chi
      square and logistic regression. RESULTS: A total of 4063 (13.4%) students
      reported that they had deliberately harmed themselves during the past 12 months.
      The acts of DSH with 1 and more than or equal to 2 times occurrence accounted for
      3.7% and 9.6% among all the respondents. The act of DSH was significantly higher
      among boys than that among girls. Rates of suicide ideation, suicide plan,
      attempted suicide and SIB in the last year were 4.5%, 1.4%, 0.6% and 4.9%,
      respectively. However no statistically significant difference was found in
      different sex. Students in the DSH group that with SIB were found to have lower
      positive coping levels (OR=0.5, 95%CI: 0.3-0.8), getting less support from
      friends (3-5 vs. less than or equal to 2: OR=0.6, 95%CI: 0.3-0.9; more than or
      equal to 6 vs. less than or equal to 2: OR=0.4, 95%CI: 0.2-0.8), with higher
      negative coping levels (OR=2.1, 95%CI: 1.2-3.7), having more serious depressive
      symptoms (OR=2.9, 95%CI: 1.6-5.2) and anxiety symptoms (OR=2.2, 95%CI: 1.2-3.8),
      having more serious sleeping problems (OR=1.7, 95%CI: 1.1-2.8) and perceived fat
      (fat vs. moderate: OR=2.0, 95%CI: 1.1-3.6) than the DSH group without SIB. The
      rates of SIB in students with DSH behavior were significantly higher than those
      in students without those behaviors (OR=4.7, 95%CI: 3.5-6.4). Psychosocial
      variables could attenuate the relationship between the DSH status and suicidal
      events (OR=3.3, 95%CI: 2.4-4.5). The DSH frequency exhibited a curvilinear
      relationship to SIB (OR=3.1-10.0) and psychosocial variables also attenuated this
      relationship (OR=2.4-5.9). CONCLUSION: It was well known that SIB was not a
      suicidal gesture but our findings suggested that the presence of DSH might
      trigger the suicidal attempts.

PMID- 22883173
TI  - [Study on the prevalence and risk factors of depressive symptoms among 'empty
      nest' and 'non-empty-nest' elderly in four provinces and cities in China].
AB  - OBJECTIVE: To investigate the prevalence and determinants of depressive symptoms
      among 'empty-nest' and 'non-empty-nest' elderly in four cities/provinces.
      METHODS: 4265 elderly aged 60 and over, were recruited with cluster sampling
      method in Shanghai, Heilongjiang, Guangdong and Shanxi province and interviewed,
      using the Geriatric Mental State Schedule and self-developed related
      questionnaire. RESULTS: (1) The prevalence of depressive symptoms for 'empty
      nest' elderly was (8.18%), significantly higher than that for 'non-empty-nest'
      elderly (P=0.019); (2) the 'empty-nest' elderly had a significantly higher
      proportion of the following factors: being male, married, with higher income
      (>=15,000 Yuan/year), living in city, with high education background, under
      employment etc. than the 'non-empty-nest' elderly (P<0.0001); (3) the 'empty
      nest' elderly had significantly higher proportions on good self-rated health
      status and life (P=0.0001, P<0.0001) as well as heavier health problems and
      economic difficulties (P=0.001, P=0.002); (4) there were significantly negative
      associations between depressive symptoms and the following 10 factors: being
      female, single, having bad self-rated health and life status, having somatic
      disease>=3, with big health problems in the last two years and loss of dearest
      persons, community engagement and involvement of religious activities.
      CONCLUSION: The 'empty-nest' elderly showed higher prevalence of having
      depressive symptoms than the 'non-empty-nest' elderly. The 'empty-nest' elderly
      had characteristics as being single, female, having adverse event etc. and should
      be under greater attention for care.

PMID- 22883174
TI  - [Depressive symptoms and associated sexual behaviors among men who have sex with
      men in Foshan, Guangdong province].
AB  - OBJECTIVE: To understand the prevalence of depressive symptoms and associated
      sexual characteristics among men who have sex with men (MSM) in Foshan, Guangdong
      province. METHODS: Respondent-driven sampling method was used to recruit MSM who
      were 18 years and older, living in Foshan longer than 6 months. Scales of
      depression, demographical information, and characteristics of sexual behaviors
      were collected using a self-designed questionnaire. Respondent-Driven Sampling
      Analysis Tool and SAS were used to generate crude and estimated population
      proportion as well as 95% confidence intervals (CI). Multivariate logistic
      regression was performed to explore potential factors associated with depressive
      symptoms. RESULTS: Among 249 respondents, the mean age (standard deviation) was
      31.9 (8.5) years, with 43.5% of them having had 7-9 years of education while
      25.9% had 10-12 years. 49.7% of the respondents were currently married. 56.7% of
      them had bisexual orientation. 42.3% of them met their sex partners in
      parks/toilet and 63.3% of them had their first sex with a female. The estimated
      prevalence of depressive symptoms was 34.8% (28.2-42.3) among MSM in Foshan.
      Younger age, lower education levels, only had oral sex, and regularly meeting
      sexual partners in parks were associated with depressive symptoms, with the
      adjusted odd ratio (95%CI) as 3.31 (1.39-7.86), 2.23 (1.01-4.93), 3.09 (1.10
      8.70) and 2.38 (1.20-4.75), respectively. CONCLUSION: Depression related symptoms
      might associate with the demographical and sexual characteristics of MSM in
      Foshan, suggesting that psychological interventions should involve components as
      demographical and sexual characteristics.

PMID- 22883175
TI  - [Prevalence of HIV infection and sexual behaviors with both men and women among
      currently married men who have sex with men].
AB  - OBJECTIVE: To find out the status of HIV infection, sexual behaviors with both
      men and women as well as condom use among currently married men who have sex with
      men (MSM) so as to document for HIV intervention targeting this sub-population,
      in Beijing, Chengdu, Harbin and Zhengzhou cities. METHODS: "Snowballing" sampling
      method was used to recruit subjects in four cities. Participants were
      investigated by anonymous questionnaire containing demographics, sexual
      orientation, both homosexual and heterosexual behaviors and condom use during the
      past 6 months. Blood samples from participants were used to test HIV antibodies.
      RESULTS: Of the 858 participants for four cities, the average age was 38.3
      (SD=9.1) years. 36.7% of them had completed the junior high school or under. The
      percentage of participants who identified themselves as homosexual, bisexual, and
      heterosexual or undecided were 40.9%, 54.3% and 4.8%, respectively. The overall
      HIV prevalence was 8.0%, and among four cities the HIV prevalence in Chengdu was
      the highest (13.3%). Results from the Multiple logistic regression analysis
      showed that never used condoms when having anal sex with men during the past 6
      months among participants who did not have a city residential card, identifying
      himself as having homosexual orientation, living in Harbin, having first anal sex
      experience before 18 years of age the range of OR value was 1.5-2.1. In addition,
      the factors associated with never using condoms in vaginal sex with women during
      the past 6 months were as follows: being over 46 years old, not having a city
      residential card, living in Beijing, identifying himself as heterosexual
      orientated or with unknown sexual orientation, never using condoms in anal sex
      with men during the past 6 months, the range of OR value was 1.7-5.9. CONCLUSION:
      The prevalence of HIV infection seemed to be quite high among those currently
      married MSM. High rates of unprotected homosexual and heterosexual behaviors
      might accelerate the spreading of HIV from currently married MSM to their wives.

PMID- 22883176
TI  - [Analysis on the frequency of urinary iodine in a population-based intervention
      study].
AB  - OBJECTIVE: Through a two-year follow up program, this study was to analyze the
      urinary iodine frequency of a cohort in the intervention trial, concerning
      different doses of salt ionization, so as to explore the selection of appropriate
      concentration of salt ionization. METHODS: A multistage cluster sampling method
      was used to select three townships in two countries for community intervention
      with different doses [(15+/-5) mg/kg, (25+/-5) mg/kg, (35+/-5) mg/kg] of salt
      ionization. RESULTS: After intervention, the median of urinary iodine was reduced
      among the population. The urinary iodine frequencies of (15+/-5) mg/kg and (25+/
      5) mg/kg among groups of children were mainly concentrated in 100-200 ug/L and
      200-300 ug/L paragraphs in A county. While the 300 ug/L paragraph had an overall
      decline in B county, the 100 ug/L and 200 ug/L paragraph ratio increased but the
      trend seemed to be slow. The 100-300 ug/L paragraph of the four treatment groups
      took a larger proportion and kept smooth in a more ideal state. However, the
      control group still maintained at above 250 ug/L level. CONCLUSION: The iodine
      supplementation should be gradually implemented in Chongqing. The doses of salt
      ionization should be reduced from the current (35+/-15) mg/kg to (25+/-5) mg/kg
      in the economically developed areas. At the same time, we need to continuously
      follow the changes of the condition.

PMID- 22883177
TI  - [Trend on vitamin C intake among Chinese population aged 50 - 79 years in 9
      provinces, from 1991 to 2009].
AB  - OBJECTIVE: To analyze the trend of dietary vitamin C intake and its food sources
      among Chinese population aged 50-79 years old in 9 provinces, from 1991 to 2009.
      METHODS: Data on twenty-four-hour dietary recall from China Health and Nutrition
      Survey (1991, 1993, 1997, 2000, 2004, 2006 and 2009) was used to identify the
      trends in vitamin C intake among Chinese population aged 50-79 years old.
      RESULTS: Totally, 24,321 adults were assessed among 7 round surveys, including
      11,739 males (48.3%) and 12,582 females (51.7%). From 1991 to 2009, the intake of
      vitamin C was reduced by 12.1 mg and 11.8 mg in rural male and female
      respectively; and the intake of vitamin C increased by 8.7 mg and 10.2 mg in
      urban males and females, respectively. Intake of vitamin C from the dark-color
      vegetables decreased by 15.1 mg and 13.9 mg in rural males and females, and it
      was increased first then decreased in both urban males and females. Vitamin C
      from the light-color vegetables kept stable during the 18 years. The intake of
      vitamin C in the southern residents aged 50-79 year-olds was significantly higher
      than that of the northern residents (except for 1997). The proportion that
      vitamin C intake reached to Chinese RNI were 19.8%-30.4% (urban males), 31.1%
      43.9% (rural males), 15.9%-24.9% (urban females), and 26.4%-38.1% (rural females)
      respectively. CONCLUSION: The present study indicated that the changing of
      vitamin C intake was different between urban and rural residents aged 50-79. The
      amount of vitamin C intake between urban and rural residents was gradually
      getting closer. However, the intake of vegetables and fruit was not sufficiency.

PMID- 22883178
TI  - [Genotypes distribution of hepatitis C virus through multi-center, large sample
      studies among chronic hepatitis C patients in Chinese Han population].
AB  - OBJECTIVE: To understand the distribution of hepatitis C virus (HCV) genotypes in
      China. METHODS: A national multi-center, large sample epidemiological survey was
      carried out and certified by an international third-party testing organization.
      Internationally accepted method for sequencing analysis of viral genotype was
      used. RESULTS: Patients were those suffered from the 4 major genotypes of chronic
      hepatitis C, including nine subtypes, which were dominated by genotype 1 (69.6%),
      with type 1b in particular (accounting for 68.38%). Among the rare gene-6, we saw
      more subtypes of 6a. In the south, central, and north areas, there was no
      significant difference seen between the south and the north areas in the
      distribution of the genotype 1. However, the rate of gene type 2a increased
      gradually from south to north. In terms of less common type of gene 3b and gene
      6, they were seen mainly in the southern provinces. CONCLUSION: In China,
      Patients with chronic hepatitis C had 4 HCV genotypes, with 9 subtypes. The
      rarely seen genotypes 3b and 6 were mainly distributed in the southern provinces.

PMID- 22883179
TI  - [Construction of surveillance and early-warning-index-system on tuberculosis in
      China].
AB  - OBJECTIVE: To establish the surveillance and warning index system corresponding
      with the epidemic characteristics of tuberculosis, in China. METHODS: Literature
      review and expert meeting were conducted to formulate the preliminary index
      system frame. Delphi method was used for screening the index and determining the
      weight of each index. RESULTS: Two-round Delphi consultations were performed. The
      activity coefficients were 87.0%, 90.0% respectively, with means of authority
      coefficient as 0.850+/-0.055 and 0.917+/-0.017, respectively. Mean scores of the
      index were 7.063+/-1.435, 8.156+/-0.611 respectively, with the means of
      coefficient of variation as 0.352+/-0.161 and 0.170+/-0.057 respectively. The
      harmony coefficients were 0.322 (chi2=499.472, P<0.05) and 0.393 (chi2=241.126,
      P<0.05) respectively. After the two-round consultation, the tuberculosis
      monitoring and warning index system was developed, including 4 first-class
      indicators, 9 second-class indicators and 48 third-class indicators. CONCLUSION:
      An index system was established for tuberculosis monitoring and early warning
      that could provide evidence for tuberculosis prevention and control as well as
      for the forecasting and warning model of the disease.

PMID- 22883180
TI  - [Impact of pregnancy terminations before 28 weeks of gestation on the overall
      prevalence of neural tube defects in two counties of Shanxi province].
AB  - OBJECTIVE: To examine the impact of pregnancy termination before 28 weeks of
      gestation on the overall prevalence of neural tube defects (NTDs). METHODS: Data
      collected during the period of 2004 and 2010 from a birth defects surveillance
      system in Pingding county and Taigu county of Shanxi province were used. Number
      of births>=28 weeks of gestation and number of cases with major birth defects
      among the births were collected. Terminations of pregnancies before 28 weeks of
      gestation due to prenatal diagnosis were also collected. The total prevalence of
      neural tube defects, prevalence before 28 weeks of gestation, and prevalence of
      >=28 weeks gestation were calculated using the total number of pregnancies of
      >=28 weeks of gestation as denominator. The prevalence data were compared to
      examine the impact of pregnancy termination on the total prevalence. The
      proportions of pregnancy terminations before 28 weeks of gestation due to
      prenatal diagnosis of an NTD against the total number of NTD cases were also
      calculated. RESULTS: During 2004-2010, 52 366 births were recorded, and 485 NTD
      cases were ascertained. The overall prevalence of NTDs was 92.6 per 10,000
      births, with prevalence of <28 weeks gestation due to pregnancy terminations as
      60.9 per 10,000 births, while the prevalence of >=28 weeks of gestation was 31.7
      per 10,000 births. NTD prevalence of >=28 weeks gestation was 66.0% lower than
      the total NTD prevalence. In the last two years, the proportion of NTDs
      ascertained >=28 weeks gestation accounted for about 40.0% of the total NTD
      cases. CONCLUSION: A birth-defect-surveillance program that covered only
      pregnancies>=28 weeks of gestation resulted in a severe underestimation of the
      total birth prevalence of NTDs, especially for anencephaly. We would recommend
      that the current national birth defects surveillance system should include
      pregnancy terminations before 28 weeks of gestation and the calculation of total
      NTD prevalence should also include these cases into the numerator, so as to
      better estimate true population NTD prevalence, upon which the related public
      health policy is based.

PMID- 22883181
TI  - [Dynamic investigation on the co-infection status of two pathogens in ticks from
      tourist point in Heilongjiang province].
AB  - OBJECTIVE: To monitor the co-infection status of Borrelia burgdorferi sensu lato
      (B.b.s.l) and spotted fever group Rickettsia (SFGR) in tourist areas of
      Heilongjiang province. METHODS: Polymerase chain reaction (PCR) was used to
      detect the 5S-23S rRNA intergenic spacer of B.b.s.l and ompA of SFGR in ticks,
      dynamically collected from tourist areas of Heilongjiang province in 2010.
      Amplification products from positive ticks were sequenced, and phylogenetic
      analysis was conducted by Mega 5.0 software package. RESULTS: 849 ticks were
      collected from two tourist points, with the dominant ticks in Tiger Mountain and
      Jingpo Lake were Ixodes persulcatus and Haemaphysalis concinna. Regarding the
      Ixodes persulcatus from Tiger Mountain, the infection rates of B.b.s.l and SFGR
      were 26.15% and 10.05%. The infection rate of SFGR was 13.33% in Haemaphysalis
      concinna and the B.b.s.l was undiscovered in the same ticks from Jingpo Lake.
      However, the co-infection could only be detected in Ixodes persulcatus of both
      tourist areas. Surveillance data showed that the major ticks were more likely to
      be appeared in July at Tiger Mountain and in June at Jingpo Lake. Data from the
      sequence analysis on B.b.s.l showed that the B.b.s.l in tourist areas could be
      classified into three different genotypes, other than B. garinii and B. afzelii.
      We first detected B. valaisiana-like group genotype in northeast of China.
      Results from the sequence analysis of SFGR positive products showed that the two
      DNA sequences of newly detected agents were completely the same as Rickettsia sp.
      HL-93 which was detected in Hulin and Rickettsia sp. H820 found in northeast,
      China. CONCLUSION: The co-infection of B.b.s.l and SFGR was detected in ticks
      from the tourist areas of Heilongjiang province, and data from the sequencing of
      specific fragment showed that various kinds of genotypes existed in this area.
      However; the rates of co-infections-different according to environment, time and
      population that contributed to the kinds of and the index of ticks existed in the
      surveys points, also the infection rate of the ticks was studied.

PMID- 22883182
TI  - [Investigation on Ehrlichia chaffeensis and Anaplasma phagocytophilum infection
      among farmers and domestic animals in rural areas of Beijing, China].
AB  - OBJECTIVE: To investigate the status of Ehrlichia (E.) chaffeensis and Anaplasma
      (A.) phagocytophilum infection among farming populations and domestic animals in
      the rural area of Beijing, China. METHODS: Blood samples from 562 farmers and 163
      blood samples including 90 goats, 71 ox and 2 dogs, were collected. Specificity
      of IgG antibodies against E. chaffeensis and A. phagocytophilum were tested by
      micro-indirect immunofluorescent assay (mIFA). 16S rRNA genes of A.
      phagocytophilum were amplified from the domestic animal blood samples and
      products were sequenced and analyzed by nested PCR. RESULTS: The positive rates
      of E. chaffeensis and A. phagocytophilum antibody were 16.5% and 14.0%
      respectively for farmers. The total positive rates of A. phagocytophilum were
      2.3% and 0 for both goats and oxen respectively. No antibody was found for the 2
      tested dogs. The PCR positive rates were 48.9% and 23.9% for goats and oxen
      respectively. Three dominant varieties of A. phagocytophilum were demonstrated in
      goats and oxen. CONCLUSION: The prevalence rates of E. chaffeensis and A.
      phagocytophilum were identified in the rural areas of Beijing.

PMID- 22883183
TI  - [Comparison on the levels of human serum antibody against Neisseria meningitidis
      serogroup C measured using serum bactericidal assay and ELISA].
AB  - OBJECTIVE: To analyze the levels of human serum antibody against Neisseria
      meningitidis serogroup C measured by serum bactericidal assay (SBA) and ELISA.
      METHODS: SBA and a modified ELISA were applied to measure the serum bactericidal
      titer and the specific concentration of immunoglobulin G (IgG) against
      meningococcal serogroup C in sera samples. Seventy-five sera were from healthy
      adults without undertaking vaccination while another 429 and 388 pre- and post
      vaccinated sera were from 143 infants and 194 young children immunized with
      conjugate vaccine or polysaccharide vaccine, respectively. Correlation between
      serum bactericidal titer and the concentration of specific IgG against
      meningococcal serogroup C was analyzed. RESULTS: The concentration of
      meningococcal serogroup C specific IgG in healthy adults showed a strong
      correlation (r=0.814 33, P<0.001) with serum bactericidal titer through linear
      regression analysis. Weak correlation was observed between SBA titers and IgG
      concentration in pre vaccinated sera of infants and children
      (conjugate/polysaccharide vaccine) (infants: r=0.140 64, P>0.100/r=0.2899,
      P<0.05; children: r=0.540 40, P<0.05/r=0.194 36, P<0.05). After immunization with
      2-dose conjugate vaccine in infants and 1-dose in children, a strong correlation
      between the two panels of results was observed (r=0.809 38, P<0.001 and r=0.837
      23, P<0.001 respectively). However after immunization with polysaccharide
      vaccine, the correlation between serum bactericidal titer and concentration of
      specific IgG was weak (r<0.50000). CONCLUSION: Among healthy adults and post
      vaccinated infants or young children immunized with conjugate vaccine, the
      concentration of specific IgG was comparable to the serum bactericidal titer
      against meningococcal serogroup C. However, it was not unfavorable to use ELISA
      as the principal means of measuring serum antibody responses to polysaccharide
      vaccine for infants under 1 year old.

PMID- 22883185
TI  - [Association between serum uric acid and short-term clinical outcome among
      patients with acute stroke].
AB  - OBJECTIVE: To investigate the association between serum uric acid (SUA) and early
      clinical outcome among patients with acute stroke. METHODS: A total of 3231 acute
      stroke patients were included in the present study. Data on demographic
      characteristics, life style risk factors, history of disease, admission SUA and
      clinical outcome at discharge were collected for all participants. Poor clinical
      outcome was defined as neurologic deficiency (NIHSS>=10) at discharge or death
      during hospitalization. RESULTS: Increased SUA level was associated with
      decreased risk of poor outcome among ischemic stroke patients. After adjustment
      for multivariate, the odds ratio (95% confidence interval) of poor outcome for
      every increased unit was 0.856 (0.795-0.898) among ischemic stroke patients.
      Logistic analysis was conducted according to quintile of SUA level, after
      adjustment for multi-variates, the odds ratio (95% confidence interval) of poor
      clinical outcome appeared to be associated with SUA of 197-241 umol/L, 242-285
      umol/L, 286-346 umol/L and >=347 umol/L, but were 0.552 (0.354-0.861), 0.417
      (0.263-0.661), 0.390 (0.241-0.630) and 0.352 (0.213-0.581), respectively in those
      acute ischemic stroke patients, when compared to those with SUA<197 umol/L. Among
      acute hemorrhagic stroke patients, after adjustment for multivariate, the odds
      ratio (95% confidence interval) of poor outcome for every increased unit was not
      significant among hemorrhagic stroke patients. According to the quintile of SUA
      level, when compared to those with SUA<150 umol/L, the odds ratio (95% confidence
      interval) of poor clinical outcomes associated with SUA of 150-185 umol/L, 186
      230 umol/L, 231-297 umol/L and >=298 umol/L, were also not significant among
      those hemorrhagic stroke patients. CONCLUSION: Elevated SUA seemed to be an
      independent predictor for short-term good clinical outcome among acute ischemic
      stroke patients.

PMID- 22883184
TI  - [A rapid screening program on the resistance to streptomycin and ethambutol in
      Mycobacterium tuberculosis isolates by PCR melting curve analysis].
AB  - OBJECTIVE: To evaluate the effects of PCR melting curve analysis assay on a rapid
      screening program regarding the resistance of Mycobacterium tuberculosis (MTB)
      clinical isolates to streptomycin and ethambutol. METHODS: A total of 331
      clinical isolates of MTB had been collected since 2007-2009 in Shenzhen.
      Mutations at codon 306, 378-380, 406 and 497 of embB gene, codon 43, 88 of rpsL
      gene, and 513-517, 905-908 region of rrs gene were detected by PCR melting curve
      analysis. Results were compared with that of conventional drug susceptibility
      test. RESULTS: Compared to drug susceptibility test, sensitivity, specificity and
      accuracy for streptomycin resistance were 78.6%, 90.1% and 86.7%, respectively
      while 83.0%, 93.3% and 91.8%, respectively for ethambutol resistance detected by
      PCR melting curve analysis. PCR melting curve method was in good agreement with
      drug susceptibility test. CONCLUSION: PCR melting curve analysis on genetic
      regions associated with resistance to streptomycin and ethambutol seemed to be a
      rapid, specific and closed-tube method so it could be used for detection of
      streptomycin and ethambutol resistance in MTB.

PMID- 22883186
TI  - [Clinical studies on different coronary artery interventional therapies through
      femoral artery or radial artery approaches].
AB  - OBJECTIVE: To compare the clinical efficacies regarding femoral artery or radial
      artery approaches on coronary artery interventional therapies. METHODS: 360
      patients were randomly divided into intervention group via femoral artery (TFI)
      or transradial coronary intervention (TRI) group. Postoperative observation on
      the two said groups of patients with vascular lesion characteristics, feasibility
      factors (success rate of interventional therapy puncture, time of operation and
      hospitalization) and complications, were made. RESULTS: There were no significant
      differences between the two groups on the characteristics of vascular lesion
      (P>0.05). Success rates of the two groups were 97.78% and 96.67% respectively.
      The differences on success rate, time of operation were not statistically
      significant (P>0.05) while the average time of puncture, the mean duration of
      hospitalization and the rates of complications were significantly different
      (P<0.05). CONCLUSION: The two methods under comparison had similar success rate
      and feasibility. However, the complications related to radial artery
      interventional therapy were much less than the femoral artery interventional
      therapy. As having better safety, radial artery interventional therapy seemed to
      have applicable value on clinical practice.

PMID- 22883187
TI  - [Eco-geographic landscapes of natural plague foci in China III. Biological
      characteristics of major DFR/MLVA-based genotypes of Yersinia pestis, China].

PMID- 22883188
TI  - [Review on the research progress of early-warning system on dengue fever].

PMID- 22883189
TI  - [Renew us concept in vitamin D nutritional status].

PMID- 22883190
TI  - [Basic principle and new strategy of endocrine therapy for breast cancer
      patients].

PMID- 22883191
TI  - [Issues of neoadjuvant therapy for postmenopausal hormone receptor-positive
      breast cancer].

PMID- 22883192
TI  - [The safety of endocrine therapy in breast cancer].

PMID- 22883193
TI  - [Mechanism of lysyl oxidase (LOX) in breast cancer invasion and metastasis].
AB  - OBJECTIVE: To investigate possible mechanism of silencing lysyl oxidase (LOX)
      gene by RNA interference affecting on invasion and metastasis of breast cancer
      cells. METHODS: LOX-RNAi-LV was designed and synthesized, which was transfected
      into breast cancer cell line MDA-MB-231. The expressions of LOX, MMP-2 and MMP-9
      were determined by Real-time PCR in MDA-MB-231 cells, and the protein expression
      of LOX was determined by Western blot. The cells migration and invasion abilities
      were measured by cell migration and invasion test. 111 cases of breast cancer
      tissue and cancer-adjacent breast tissues and 20 cases of benign lesion tissues
      of LOX, MMP-2 and MMP-9 were detected by immunohistochemistry, and the
      relationship of LOX and clinicopathological characteristics was analyzed.
      RESULTS: The expression levels of LOX mRNA and protein were down-regulated
      obviously after transfecting LOX-RNAi-LV, with the inhibition rate 89.2% +/- 1.3%
      and 84.4% +/- 0.4% respectively. The relative expressions of MMP-2 and MMP-9 mRNA
      were 0.496 +/- 0.021 and 0.571 +/- 0.099 in RNAi group, which was significantly
      lower than that in negative control group (0.846 +/- 0.047, 0.786 +/- 0.042) and
      blank control group (1.000 +/- 0.000, 1.000 +/- 0.000) (both P < 0.05). Cell
      migration and invasion test showed the average cell numbers per field in the
      group RNAi were 47 +/- 2 and 63 +/- 2, was significantly lower than that in
      negative control group (100 +/- 1, 118 +/- 2) and blank control group (100 +/- 1,
      118 +/- 2) (both P < 0.05). The expression of LOX protein in breast cancer,
      cancer-adjacent breast tissues and benign breast tumor were 48.6% (54/111), 26.1%
      (29/111), 20.0% (4/20), the expression of LOX protein in breast cancer was
      significantly higher than that in cancer-adjacent breast tissues and benign
      lesion tissues (P = 0.019). The expression of LOX protein was associated with
      clinical stage, lymph node metastasis, tumor size. Correlation analysis showed
      that LOX protein expression was significantly positive correlation with MMP-2 (r
      = 0.262, P = 0.005) and MMP-9 (r = 0.424, P = 0.000). CONCLUSION: LOX can promote
      invasion and metastasis of breast cancer; LOX and MMP-2, MMP-9 may have a
      synergistic role in promoting invasion and metastasis of breast cancer.

PMID- 22883194
TI  - [Effects of single versus combined use of trastuzumab and cantide on breast
      cancer cells SKBR3 over-expressing HER2].
AB  - OBJECTIVE: To evaluate the in vitro cytotoxic effects of cantide or herceptin on
      human breast cancer SKBR3 cells over-expressing HER2. METHODS: The distribution
      of HER2 and hTERT protein in SKBR3 cells and the effects of cantide and/or
      herceptin on the subcellular localization of HER2 and hTERT were observed by
      indirect immunofluorescent assay. The inhibition rate of herceptin and/or cantide
      at different concentrations on SKBR3 cells was detected by MTT assay. And the
      apoptotic rate of cells was evaluated by flow cytometer. RESULTS: (1) The
      expressions of both HER2 and hTERT proteins in SKBR3 cells were found. HER2
      protein was predominant in cell membranes while hTERT protein in nuclei. After
      the addition of herceptin, the cytoplasmic migration of HER2 was found while
      there was no distinct location change of cantide. (2) In MTT assay, the single
      use of cantide or herceptin and the combined use of both produced inhibitory
      effects on SKBR3 cells while the inhibition rate was higher for combined use. The
      inhibitory effects became additive in the combined use of 0.4 umol/L cantide and
      0.85 ug/ml herceptin. And there were synergistic effects in the combined use of
      0.4 umol/L cantide and 1.70, 3.40, 6.88 or 13.75 ug/ml herceptin. (3) The
      apoptotic rate was 25.75% for cantide alone, 11.26% for herceptin alone and
      41.41% for their combined use (apoptotic cells predominant in advanced stage).
      CONCLUSION: Due to different localizations, cantide and herceptin have different
      action sites in their combined use. When in single use, the inhibition rate is
      linearly correlated with the concentration of herceptin or cantide. And their
      combined use produces additive or synergistic antitumor effects on SKBR3 breast
      cancer cells.

PMID- 22883195
TI  - [Depot-specific expression of caveolin-1 in human adipose tissue and their
      relationship with obesity and insulin resistance].
AB  - OBJECTIVE: To explore the depot-specific mRNA and protein expression of caveolin
      1 (CAV-1) in human subcutaneous and omental adipose tissues and analyze their
      relationship with obesity and insulin resistance. METHODS: A total of 41 subjects
      with normal glucose regulation were recruited. Among them, there were 29 cases
      with normal body mass index (BMI) and 12 cases with BMI >= 24 kg/m(2). All were
      scheduled to undergone selective abdominal operations. The levels of fasting
      insulin (FINS) were measured by chemiluminescence enzyme-linked immunosorbent
      assay (ELISA) kit. Fasting plasma glucose (FPG) was tested by glucose oxidase and
      home model insulin resistance index (HOMA-IR) calculated. Real-time polymerase
      chain reaction (RT-PCR) and Western blotting were employed to assess the relative
      mRNA and protein expression of caveolin-1 in subcutaneous and omental adipose
      tissues. And the mRNA and protein expression of caveolin-1 from different fat
      depots were compared and their correlations with BMI and HOMA-IR analyzed.
      RESULTS: (1) FINS and HOMA-IR were significantly higher in the overweight and
      obesity group than those in the normal BMI group (FINS: (8.82 +/- 3.79) mU/L vs
      (6.43 +/- 4.38) mU/L, P < 0.05, HOMA-1R: 1.91 +/- 0.85 vs 1.36 +/- 0.72, P <
      0.05). (2) The normal BMI group patients had the higher expression levels of
      caveolin-1 mRNA in omental adipose tissue than overweight counterparts (2.84 +/-
      0.86 vs 1.02 +/- 0.36, P < 0.01). But the difference in subcutaneous adipose
      tissue was not significant (P > 0.05). (3) The caveolin-1 protein expression in
      omental adipose tissue of the normal BMI group was higher than that of overweight
      patients (1.68 +/- 0.67 vs 0.73 +/- 0.29, P < 0.05). And the difference between
      two groups was not significant (P > 0.05). (4)The expressions of caveolin-1 mRNA
      in omental adipose tissue were negatively correlated with BMI, waist
      circumstance, triglyceride and HOMA-IR (r = -0.441, -0.615, -0.539, -0.688, P <
      0.05). No correlations were found between the expressions of caveolin-1 mRNA in
      subcutaneous adipose tissue with BMI, waist circumstance and HOMA-IR (P > 0.05).
      CONCLUSION: Differential depot-specific expressions of caveolin-1 are present in
      human subcutaneous and omental adipose tissues. A low expression of caveolin-1 in
      omental adipose tissue may contribute to the pathogenesis of obesity and insulin
      resistance.

PMID- 22883196
TI  - [Expression and significance of programmed cell death 5 in patients of branchial
      asthma].
AB  - OBJECTIVE: To explore the expression and significance of serum programmed cell
      death 5 (PDCD5) in patients with bronchial asthma. METHODS: From June to December
      2011, a total of 40 adults with bronchial asthma treated in Peking University
      Third Hospital were enrolled. Among them, the categories were acute phase (n =
      12), chronic phase (n = 14) and remission phase (n = 14). Fifteen healthy adults
      were selected into the control group. The percentages of peripheral blood
      neutrophils and eosinophils were collected and detected for each patient. Serum
      PDCD5 was detected with enzyme-linked immunosorbent assay (ELISA) and asthma
      control test (ACT) questionnaire filled in. The relevant pulmonary functional
      indicators were analyzed with a pulmonary spirometer. Two-independent sample t
      test and Pearson's correlation analysis were used for statistical analysis.
      RESULTS: No significant difference was found between two groups with regards to
      the percentages of peripheral blood eosinophils and neutrophils (all P > 0.05).
      Serum PDCD5 was significantly higher in the patient group ((47.7 +/- 29.6) vs
      (19.3 +/- 9.8) ug/L, P < 0.05). Patients of chronic and acute phases showed a
      significant higher expression in PDCD5 than the remission phase ((55.2 +/- 24.5)
      & (68.5 +/- 22.1) vs (16.0 +/- 7.9) ug/L, both P < 0.05). Serum PDCD5 of
      asthmatics showed a negative correlation with FEV(1)%, FEV(1)/FVC ratio and ACT
      scores (r = -0.539 to -0.798, all P < 0.05). CONCLUSIONS: PDCD5 participates in
      the inflammatory process of asthmatic airway. Its abnormal expression may be
      associated with the uncontrolled state of asthmatics. It may serve as an
      indicator of assessing the levels of asthma control or a target for the treatment
      of asthma.

PMID- 22883197
TI  - [Distinguishing central from obstructive sleep apnea with chest wall surface
      electrodes].
AB  - OBJECTIVE: To determine whether or not diaphragm electromyography recorded from
      chest wall surface electrodes (EMGsur) can be used to distinguish central from
      obstructive sleep apnea. METHODS: Ten patients (age (44 +/- 10) years, body mass
      index (25.9 +/- 1.8) kg/m2) with suspected obstructive sleep apnea referred from
      Guangzhou Institute of Respiratory Disease were studied between January and
      September 2009. EMGsur and diaphragm electromyography from esophageal electrode
      (EMGeso) were recorded during conventional overnight full polysomnography. And
      chest-abdominal movement was measured with chest and abdominal bands. RESULTS:
      High-quality EMGsur and EMGeso were recorded in all subjects except for one who
      could not tolerate a multipair esophageal electrode. Excellent correlation was
      found between EMGsur and EMGeso during sleep including apnea events (r = 0.81 +/-
      0.06, P < 0.05). The central sleep apnea events diagnosed by EMGeso were exactly
      the same as those diagnosed by EMGsur. However, the central sleep apnea events
      diagnosed by EMGsur were less than those diagnosed by conventional thoracic
      abdominal bands (7 +/- 11 vs 28 +/- 31, P < 0.05). CONCLUSION: EMGsur may be used
      to distinguish central from obstructive sleep apnea events.

PMID- 22883198
TI  - [Meta-analysis of mild hypothermia for gestational age over 35-week newborns with
      hypoxic-ischemic encephalopathy].
AB  - OBJECTIVE: To determine the effects of therapeutic hypothermia (TH) in
      encephalopathic asphyxiated newborn infants on mortality, long-term
      neurodevelopmental disability and side effects by summarizing the data of hypoxic
      ischemic encephalopathy(HIE) newborns undergoing mild hypothermia using meta
      analysis. METHODS: The standard searching strategy of the Neonatal Review Group
      as outlined in the Cochrane Library was used to retrieve all clinical literatures
      about TH on HIE. RevMan 5.1 software was used to perform the meta-analysis of
      target papers. The primary outcome measure was a combination of death and severe
      major neurodevelopmental disabilities at 18 - 24 months of age. Secondary
      outcomes included mortality, cerebral palsy (CP), neurodevelopmental delay,
      blindness, deafness and main side effects of cooling therapy. RESULTS: A total of
      276 papers fulfilled the search strategy and 11 trials were included. Overall TH
      resulted in a statistically significant and clinically important reduction in the
      combined outcome of death or major neurodevelopmental disabilities to 18-24
      months of age (RR = 0.76, 95%CI: 0.68 - 0.84, P < 0.01). Moreover, as compared
      with the control group, TH significantly decreased the incidence of mortality (RR
      = 0.76, 95%CI: 0.65 - 0.90, P < 0.01), psychomotor development index(RR = 0.69,
      95%CI: 0.55 - 0.87, P < 0.01), mental development index (RR = 0.66, 95%CI: 0.53 -
      0.83, P < 0.01), CP (RR = 0.70, 95%CI: 0.54 - 0.91, P < 0.01) and blindness (RR =
      0.54, 95%CI: 0.33 - 0.90, P < 0.05)except for severe hearing loss (deafness) (RR
      = 0.69, 95%CI: 0.35 - 1.34, P = 0.3000) in survivors. Adverse effects included
      significant thrombocytopenia in the TH group (P = 0.0400) but without deleterious
      consequences. There were no significant differences in arrhythmia, coagulopathy,
      hypotension requiring inotropic supports, sepsis and pulmonary hypertension
      between the TH and control groups (all P > 0.05). CONCLUSIONS: Mild hypothermia
      is effective in reducing death and major disabilities in infants with moderate-to
      severe HIE without significant side effects. Infants presenting within the first
      hours after birth with the signs and symptoms of moderate-to-severe
      encephalopathy should be cooled in accordance with the established protocols of
      previous randomized controlled trials.

PMID- 22883199
TI  - [Effects of hOCT1 and ABCB1 gene on the efficacy of imatinib mesylate in chronic
      myelocytic leukemia].
AB  - OBJECTIVE: To detect the expression of hOCT1 and ABCB1 in marrow cells and
      examine the efficacy of imatinib mesylate (IM) in patients with chronic
      myelocytic leukemia (CML). METHODS: hOCT1 and ABCB1 gene in 90 samples with
      chronic phase CML diagnosed at our hospital from January 2008 and June 2011 were
      detected by taqman probe real-time reverse transcription-PCR (RT-PCR). The
      samples were divided into 3 groups: drug-resistant group (n = 17), partial
      cytological remission (PCyR) group (n = 11) and complete cytogenetic remission
      (CCR) group (n = 62) according to IM efficacy and 3 - 6, 7 - 12, 13 - 24, 25 -
      48, > 48 months five groups (n = 21, 8, 15, 29, 17) according to IM treatment
      course. The relationship was explored between two genes and different disease
      states, course of treatment and time from first CCR. RESULTS: The hOCT1 gene mRNA
      expression of CCR group (-3.77 +/- 0.55) was higher than drug-resistant group (
      4.12 +/- 0.47) and PCyR group (-4.24 +/- 0.35) (P = 0.047, 0.019). The ABCB1 gene
      mRNA expression of drug-resistant group (-2.93 +/- 0.49) was higher than CCR
      group (-3.02 +/- 0.56) and PCyR group (-3.51 +/- 0.45) (P = 0.045, 0.021). The
      hOCT1 and ABCB1 mRNA expressions showed no significant difference between five
      groups divided by IM treatment course (P = 0.270, 0.367). The median follow-up
      time was 30 (3 - 117) months. In same IM treatment course patients, the CCR rates
      in hOCT1 and ABCB1 low-expression groups were higher than that in high-expression
      groups separately (P = 0.006, 0.049). CONCLUSIONS: The expression levels of hOCT1
      and ABCB1 vary in different disease states of patients on IM. And these two genes
      may influence the time from first CCR. But there is no significant relationship
      with course of the treatment.

PMID- 22883200
TI  - [Application of 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography in preoperative assessment of hilar cholangiocarcinoma].
AB  - OBJECTIVE: To evaluate the value of positron emission tomography/computed
      tomography (PET/CT) in the preoperative assessment of hilar cholangiocarcinoma
      (HC). METHODS: A retrospective analysis was performed for 32 HC patients. There
      were 14 females and 18 males with a mean age of 56 years old. All cases were
      confirmed by surgery, pathology or other diagnostic modalities. 18F
      fluorodeoxyglucose (FDG) PET/CT was performed preoperatively in all patients. The
      images were interpreted and compared with the operative and pathological outcomes
      in each case. RESULTS: Among them, according to the Bismuth-Corlette
      classification, the number of types I, II, IIIa, IIIb and IV patients, were 3, 2,
      4, 8 and 15 respectively. Radical tumor resection was performed in 16 patients.
      Among them, 3, 2, 1, 7 and 3 patient belonged to types I, II, IIIa, IIIb and IV
      respectively. Seven patients underwent palliative surgery and 9 had only surgical
      exploration. The detecting accuracy of PET/CT in primary tumors Bismuth-Corlette
      classification reached 81.25% (26/32). The sensitivity, specificity and accuracy
      of PET/CT in detecting lymph node metastasis and distant metastasis were 64.7%,
      86.7%, 75.0% and 41.7%, 95.0%, 75.0% respectively. The concordance rate of
      preoperative evaluation of respectability by PET/CT and intraoperative evaluation
      was 75.0%. No significant difference existed between PET/CT and the surgical and
      histopathologic findings in the evaluation of curative resectability for HC (chi2
      = 0.125, P > 0.05). CONCLUSION: 18F-FDG PET/CT is of great value in the diagnosis
      of HC, as well as in detecting lymph node metastasis and distant metastasis. Thus
      18F-FDG PET/CT is helpful in the preoperative assessment of resectability for HC.

PMID- 22883201
TI  - [Relationship of cytomegalovirus, Chlamydia pneumoniae and herpes simplex virus
      type 2 infections with preeclampsia].
AB  - OBJECTIVE: To explore the potential relationship of cytomegalovirus (CMV),
      Chlamydia pneumoniae (CP) and herpes simplex virus type 2 (HSV-2) in inflammation
      and preeclampsia. METHODS: Fifty-two pregnant women with preeclampsia and 34 with
      uncomplicated pregnancy in the third trimester were recruited. The exclusions
      included uterine contractions, multiple pregnancies, rupture of membranes,
      symptomatic infectious diseases, medical diseases and antibiotics or hormones
      users. Samples of maternal blood were harvested from two groups. Serum levels of
      CMV, CP, and HSV-2 IgM and IgG antibodies as well as high-sensitivity C-reactive
      protein (hs-CRP) and interleukin-6 (IL-6) were determined by enzyme-linked
      immunosorbent assay (ELISA) in preeclampsia and normal pregnancy controls.
      RESULTS: (1) Recent infections of CMV, CP and HSV-2 were not more common in
      patients with preeclampsia versus normal pregnancy. The prevalence rates of long
      dated CMV, CP and HSV-2 infection were 94.2% (49/52), 53.9% (28/52) and 3.9%
      (2/52) in preeclampsia group versus 100.0% (34/34), 55.9% (19/34) and 5.9% (2/34)
      in control group. No significant difference existed between two groups (P >
      0.05). (2) Maternal serum concentrations of IL-6 and hs-CRP in patients with
      preeclampsia were significantly higher than that in normal pregnancy women ((7.2
      +/- 2.1) ng/L and (6.8 +/- 5.6) mg/L vs (6.2 +/- 1.8) ng/L and (4.6 +/- 3.0)
      mg/L, both P < 0.05). CONCLUSION: Excessive inflammatory reactions are present in
      women with preeclampsia. But previous infections, as measured by IgM and IgG
      antibody seropositivity to CMV, CP and HSV-2, are not correlated with
      preeclampsia in the third trimester.

PMID- 22883202
TI  - [Comparative study of clinical efficacy between surgery by intraoperative MRI
      navigation versus traditional surgical resection for malignancy of parapharyngeal
      space].
AB  - OBJECTIVE: To investigate the clinical efficacy between mobile intraoperative
      magnetic resonance imaging (iMRI) navigation with a high field strength and
      routine surgical resection for malignancy of parapharyngeal space. METHODS: The
      surgical efficacy indexes of patients at our hospital during the time range from
      February 2010 to February 2011 were compared between two groups consisting of 29
      or 42 individuals undergoing surgery with the assistance of the technique of iMRI
      navigation with a high field strength 1.5T or routine operation. RESULTS: No
      difference existed between two groups in terms of age, gender, maximal diameter
      of tumors, tumor stages, surgical approach or pathologic diagnosis (P > 0.05).
      The operative duration of the group by iMRI navigation was more than the group of
      routine operation ((3.1 +/- 0.6) h vs (2.7 +/- 0.7) h, P < 0.05). And the
      hemorrhagic loss ((185 +/- 20) ml vs (230 +/- 22) ml), the volume of drainage in
      72 hours, the positive rate of initial surgical margins, the postoperative
      hospital stay ((9.1 +/- 2.1) d vs (10.3 +/- 2.3) d) and the complication
      incidence rate (3.4% vs 9.5%) were less (all P < 0.05). CONCLUSION: The operation
      by the iMRI navigation offers a much better clinical efficacy than the
      traditional surgery in the resection of malignancy of parapharyngeal space.

PMID- 22883203
TI  - [Toll-like receptor 4 expression of human peripheral blood mononuclear cells
      treated by recombinant hIFN-alpha-2b-BCG and its role of immune activation].
AB  - OBJECTIVE: To examine the toll-like receptor 4 (TLR4) expression of human
      peripheral blood mononuclear cells (hPBMC) treated with recombinant bacillus
      Calmette-Guerin (rBCG) and its role of immune activation. METHODS: hPBMC was
      treated with recombinant human interferon (hIFN)-alpha-2b-BCG (rBCG) or wild BCG
      (wBCG) in vitro and the TLR4 expression detected by flow cytometry. The TLR4
      functional blocking antibodies were applied for intervening the TLR4 signaling
      pathway of hPBMC. Then rBCG, wBCG, hIFN-alpha-2b and phosphate-buffered solution
      (PBS) were used to stimulate the hPBMC of blocking and non-blocking groups. The
      changes of human tumor necrosis factor-alpha (hTNF-alpha), human interleukin-12
      (hIL-12) and hIFN-gamma between the blocking and non-blocking groups by ELISA.
      RESULTS: The expression of TLR4 in hPBMC treated with rBCG or wBCG were stronger
      than that treat with PBS (all P < 0.05). In TLR4 non-blocking groups the
      expressions of hTNF-alpha and hIFN-gamma were rBCG group > wBCG group > hIFN
      alpha-2b group > PBS group, the expressions of hIL-12 was hIFN-alpha-2b group >
      PBS group > rBCG group > wBCG group (all P < 0.05). Application of TLR4
      functional blocking antibodies to intervene hPBMC 48 h, comparing the changes in
      rBCG group, wBCG group, hIFN-alpha-2b group and PBS group, the expressions of
      hIFN-gamma in TLR4 blocking groups (27.3 +/- 1.2, 20.6 +/- 0.9, 20.3 +/- 0.8,
      18.4 +/- 0.7)were significantly inhibited than those in non-blocking groups (84.6
      +/- 1.3, 34.0 +/- 1.0, 24.9 +/- 0.9, 22.9 +/- 0.7) (all P < 0.05). The
      expressions of hTNF-alpha in TLR4 blocking groups (1431 +/- 28, 1032 +/- 21, 104
      +/- 6, 109 +/- 4) were significantly inhibited than those in non-blocking groups
      (1553 +/- 28, 1065 +/- 31, 343 +/- 6, 299 +/- 4) (all P < 0.05). The expressions
      of hIL-12 in TLR4 blocking groups (0.646 +/- 0.005, 0.592 +/- 0.015, 0.638 +/-
      0.008, 0.595 +/- 0.019) were significantly inhibited than those in non-blocking
      groups (1.120 +/- 0.012, 0.946 +/- 0.015, 1.254 +/- 0.011, 1.112 +/- 0.024) (all
      P < 0.05). CONCLUSION: rBCG regulates the secretion of Th1 cytokines through the
      TLR4 signaling pathway.

PMID- 22883204
TI  - [Effects of hypercholesterolemia on contrast media-induced nephrotoxicity in
      rats].
AB  - OBJECTIVE: To explore the effects of short- and long-term dietary
      hypercholesterolemia on contrast media-induced nephrotoxicity in rats. METHODS:
      The male Wistar rats were fed either a normal rodent diet or a high cholesterol
      diet. At the end of 2 and 8 weeks, 8 rats from each group received a tail vein
      injection of either Iohexol injection (groups NC and HC) or vehicle (groups N and
      H). Blood lipid, renal function, renal hemodynamics, renal and urinary
      prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), renal nitric oxide and
      malondialdehyde (MDA) were determined at Day 1 following the administration of
      contrast media. RESULTS: The dosing of contrast media induced obviously increased
      serum creatinine compared with normal rats ((185 +/- 28) vs (53 +/- 3) umol/L, P
      < 0.01) and severe renal tubular necrosis in rats with a high cholesterol diet
      for 8 weeks but did not in normal-diet rats or rats with a high cholesterol diet
      for 2 weeks. The renal and urinary levels of PGE2 and TXB2 increased
      significantly in rats of groups H and HC at the end of 8 weeks. The renal
      production of nitric oxide decreased while the concentration of MDA increased
      markedly in groups HC and H at the end of 8 weeks. CONCLUSION: Long-term
      hypercholesterolemia appears to be a risk factor of contrast media-induced acute
      renal failure. And it may be associated with the disorder of intrarenal
      prostaglandins and the abnormality of renal nitric oxide system as induced by
      lipid peroxidation.

PMID- 22883205
TI  - [Experimental study of hyaluronic acid on the biomechanical compliance of porcine
      acellular dermal transplantation].
AB  - OBJECTIVE: To explore the effect on biomechanical compliance after an addition of
      hyaluronic acid (HA) in transplantation of porcine acellular dermal matrix (PADM)
      with skin autograft. METHODS: Ten Japanese white rabbits were used as
      experimental animal, the dorsa of rabbits was symmetrically divided into four
      area, and then grouping was randomized. Full-thickness skin defects were created
      in Group A to Group C, and Group D was blank group with normal skin. The
      following procedures were performed: Group A: implanted with HA+PADM+ thin skin
      autografts, GroupB: implanted with PADM+ thin skin autografts and Group C: skin
      autografts, except for Group D. The wound tissue specimens were harvested at 70
      days postoperatively, and they were recorded contracture rates of the grafts and
      the biomechanical compliance by Instron biomechanics tensiometer. The expression
      of collagens I and III in dermal fibroblasts of each group was determined by
      Western blot. RESULTS: On postoperation day 70, the grafts contracture rates in
      Group A to Group C were 10.2% +/- 0.6%, 36.6% +/- 0.8%, 32.7% +/- 1.4%
      respectively, there were notable significant difference among three groups (P =
      0.000). Under the same tension, there was no significant difference in strain
      between Groups A and D ((83 +/- 8) vs (81 +/- 5) kPa, P = 0.552). Some
      significant difference in strain existed between Groups B and D ((215 +/- 9) vs
      (81 +/- 5) kPa, P = 0.000). The strain of Group C ((106 +/- 7) kPa) was between
      Groups B and D, and significant strain difference existed among them (P = 0.000).
      The expressions of collagens I and III in Group A were higher than those in Group
      B, while the ratio of collagens I to III in Group A was lower than that in Group
      B. CONCLUSION: Topical HA may be used to increase the expressions of type I and
      III collagen, decrease the ratio of collagen type I/III, and enhance the
      biomechanics performances of transplanted skin.

PMID- 22883206
TI  - Incorporating published univariable associations in diagnostic and prognostic
      modeling.
AB  - BACKGROUND: Diagnostic and prognostic literature is overwhelmed with studies
      reporting univariable predictor-outcome associations. Currently, methods to
      incorporate such information in the construction of a prediction model are
      underdeveloped and unfamiliar to many researchers. METHODS: This article aims to
      improve upon an adaptation method originally proposed by Greenland (1987) and
      Steyerberg (2000) to incorporate previously published univariable associations in
      the construction of a novel prediction model. The proposed method improves upon
      the variance estimation component by reconfiguring the adaptation process in
      established theory and making it more robust. Different variants of the proposed
      method were tested in a simulation study, where performance was measured by
      comparing estimated associations with their predefined values according to the
      Mean Squared Error and coverage of the 90% confidence intervals. RESULTS: Results
      demonstrate that performance of estimated multivariable associations considerably
      improves for small datasets where external evidence is included. Although the
      error of estimated associations decreases with increasing amount of individual
      participant data, it does not disappear completely, even in very large datasets.
      CONCLUSIONS: The proposed method to aggregate previously published univariable
      associations with individual participant data in the construction of a novel
      prediction models outperforms established approaches and is especially worthwhile
      when relatively limited individual participant data are available.

PMID- 22883208
TI  - Evaluation of a posterior vitreous detachment.

PMID- 22883207
TI  - A combination of modified atmosphere and antimicrobial packaging to extend the
      shelf-life of beefsteaks stored at chill temperature.
AB  - An antimicrobial polyethylene (PE) film was obtained by coating a nisin-based
      antimicrobial solution. PE sheets were coated on both sides and were used for the
      packaging of beefsteaks to be stored in air or modified atmosphere packaging
      (MAP, 60% O2-40% CO2). Microbial populations, species diversity, headspace
      volatile organic compounds, colour and sensory properties were monitored after 0,
      1, 7 and 12 days of storage at 4  degrees C. The viable counts showed that there
      was an effect of MAP and antimicrobial film on the development of all the
      spoilage associated microbial populations. Carnobacterium spp., Brochothrix
      thermosphacta, Pseudomonas fragi and Rhanella aquatilis were found in most of the
      samples. C. maltaromaticum was identified in MRS bulk cells from samples stored
      in air as well as MAP. Quantitative data of headspace-SPME-GC/MS analysis showed
      that during storage the production of volatile organic compounds (VOCs) was
      affected by the use of the treated film and the MAP storage. Compounds such as
      phenylethylalcohol, nonanal, decanal and ethylbutanoate were produced only from 7
      to 12 day of storage and only in the samples stored in air. In agreement with the
      microbiological and VOCs data, the meat stored in active packaging scored the
      best rankings in the sensory evaluation. Principal component analysis of
      microbial, sensory and instrumental data showed that beefsteaks stored with the
      combination of MAP and active packaging for 12 days at 4  degrees C differed from
      the other samples that were more associated to high microbial loads, VOCs
      concentration and meat off odour perception. In conclusion, the antimicrobial
      sheets in combination with MAP storage at 4  degrees C were effective for the
      storage of beefsteaks by retarding the growth of spoilage bacteria, determining
      lower concentration of VOCs and keeping acceptable levels of colour and other
      sensory parameters for more than 10 days.

PMID- 22883209
TI  - Global Change adaptation in water resources management: the Water Change project.
AB  - In recent years, water resources management has been facing new challenges due to
      increasing changes and their associated uncertainties, such as changes in
      climate, water demand or land use, which can be grouped under the term Global
      Change. The Water Change project (LIFE+ funding) developed a methodology and a
      tool to assess the Global Change impacts on water resources, thus helping river
      basin agencies and water companies in their long term planning and in the
      definition of adaptation measures. The main result of the project was the
      creation of a step by step methodology to assess Global Change impacts and define
      strategies of adaptation. This methodology was tested in the Llobregat river
      basin (Spain) with the objective of being applicable to any water system. It
      includes several steps such as setting-up the problem with a DPSIR framework,
      developing Global Change scenarios, running river basin models and performing a
      cost-benefit analysis to define optimal strategies of adaptation. This
      methodology was supported by the creation of a flexible modelling system, which
      can link a wide range of models, such as hydrological, water quality, and water
      management models. The tool allows users to integrate their own models to the
      system, which can then exchange information among them automatically. This
      enables to simulate the interactions among multiple components of the water
      cycle, and run quickly a large number of Global Change scenarios. The outcomes of
      this project make possible to define and test different sets of adaptation
      measures for the basin that can be further evaluated through cost-benefit
      analysis. The integration of the results contributes to an efficient decision
      making on how to adapt to Global Change impacts.

PMID- 22883211
TI  - Assessing EMS scope of practice for utility and risk: the New Mexico EMS
      Interventions Assessment Project, Phase One results.
AB  - INTRODUCTION: Few emergency medical services (EMS) interventions in New Mexico
      have been assessed for efficacy, potential harm, or potential benefit. There is
      concern that many interventions added over the years may be outdated, harmful, or
      ineffective in the EMS setting. A formal process for reviewing the state EMS
      scope of practice using literature review and expert consensus is discussed. In
      Phase One of the project, interventions in the New Mexico EMS scope of practice
      were prioritized for further review by surveying a national cadre of EMS experts
      to evaluate EMS interventions using a utilitarian harm/benefit metric. METHODS:
      An electronic survey based on the 2010 New Mexico EMS Scope of Practice statute
      was administered from March through June, 2011. A national cadre of 104
      respondents was identified. Respondents were either State EMS medical directors
      or EMS fellowship directors. Respondents were asked to rate the potential harm
      and the potential benefit of specific EMS interventions on a 5-point ordinal
      scale. Median harm and benefit scores were calculated. RESULTS: A total of 88
      completed surveys were received following 208 emailed invitations to 104
      respondents (43% response rate). Twenty-two (22) highest-priority interventions
      (those with a harm/benefit median score ratio of >1) were identified. Seven
      additional second-priority interventions were also identified. These
      interventions will be advanced for formal literature review and expert consensus.
      CONCLUSIONS: The New Mexico EMS Interventions Project offers a novel model for
      assessing a prehospital scope of practice.

PMID- 22883210
TI  - Selective loss of noradrenaline exacerbates early cognitive dysfunction and
      synaptic deficits in APP/PS1 mice.
AB  - BACKGROUND: Degeneration of the locus coeruleus (LC), the major noradrenergic
      nucleus in the brain, occurs early and is ubiquitous in Alzheimer's disease (AD).
      Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive
      deficits in several transgenic mouse models of AD. Because the LC contains
      multiple neuromodulators known to affect amyloid beta toxicity and cognitive
      function, the specific role of noradrenaline (NA) in AD is not well understood.
      METHODS: To determine the consequences of selective NA deficiency in an AD mouse
      model, we crossed dopamine beta-hydroxylase (DBH) knockout mice with amyloid
      precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and
      PS1. Dopamine beta-hydroxylase (-/-) mice are unable to synthesize NA but
      otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal
      long-term potentiation, and synaptic protein levels were assessed. RESULTS: The
      modest impairments in spatial memory and hippocampal long-term potentiation
      displayed by young APP/PS1 or DBH (-/-) single mutant mice were augmented in DBH
      (-/-)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of
      total calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate
      receptor 2A and increased N-methyl-D-aspartate receptor 2B levels and were
      independent of amyloid beta accumulation. Spatial memory performance was partly
      improved by treatment with the NA precursor drug L-threo-dihydroxyphenylserine.
      CONCLUSIONS: These results indicate that early LC degeneration and subsequent NA
      deficiency in AD may contribute to cognitive deficits via altered levels of
      calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptors
      and suggest that NA supplementation could be beneficial in early AD.

PMID- 22883212
TI  - Community influences on adolescents' use of home-brewed alcohol in rural South
      Africa.
AB  - BACKGROUND: Alcohol represents a major public health challenge in South Africa,
      however little is known about the correlates of alcohol use among rural
      adolescents. This article examines community influences on adolescents' use of
      home-brewed alcohol in a rural region of South Africa. METHOD: A total of 1600
      high school adolescents between 11 and 16 years of age participated in this
      study. Seven hundred and forty (46.3%) were female and 795 (49.7%) were male.
      Data on gender were missing for 65 students (4.0% of the sample). The age range
      was 11-29 years (mean age 16.4 years; Standard deviation = 2.79). A survey
      questionnaire on adolescent risk behavior that examined adolescents' use of
      alcohol and various potential community influences on alcohol use was
      administered. Factor analysis was used to group community-level variables into
      factors. Multiple logistic regression techniques were then used to examine
      associations between these community factors and adolescents' use of home-brewed
      alcohol. RESULTS: The factor analysis yielded five community-level factors that
      accounted for almost two-thirds of the variance in home-brewed alcohol use. These
      factors related to subjective adult norms around substance use in the community,
      negative opinions about one's neighborhood, perceived levels of adult antisocial
      behavior in the community, community affirmations of adolescents, and perceived
      levels of crime and violence in the community (derelict neighborhood). In the
      logistic regression model, community affirmation was negatively associated with
      the use of home-brew, whereas higher scores on "derelict neighborhood" and "adult
      antisocial behavior" were associated with greater odds of drinking home-brew.
      CONCLUSION: Findings highlight community influences on alcohol use among rural
      adolescents in South Africa. Feeling affirmed and valued by the broader community
      appears to protect adolescents against early alcohol use. In contrast,
      perceptions of high levels of adult anti-social behavior and crime and violence
      in the community are significant risks for early alcohol initiation. Implications
      of these findings for the prevention of alcohol use among adolescents in rural
      communities are discussed.

PMID- 22883213
TI  - New alloferon analogues: synthesis and antiviral properties.
AB  - We have extended our study on structure/activity relationship studies of insect
      peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by
      evaluating the antiviral effects of new alloferon analogues. We synthesized 18
      alloferon analogues: 12 peptides with sequences shortened from N- or C-terminus
      and 6 N-terminally modified analogues H-X(1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly
      Val-His-Gly-OH, where X(1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe(p-Cl)
      (17), and Phe(p-OMe) (18). We found that most of the evaluated peptides inhibit
      the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and
      LLC-MK(2) cells. Our results indicate that the compound [3-13]-alloferon (1)
      exhibits the strongest antiviral activity (IC(50) = 38 MUM) among the analyzed
      compound. Moreover, no cytotoxic activity against the investigated cell lines was
      observed for all studied peptides at concentration 165 MUM or higher.

PMID- 22883215
TI  - Treatment of metastatic cervical cancer: future directions involving targeted
      agents.
AB  - Cervical cancer is the third most common cause of female cancer mortality, and it
      remains a major health problem in populations with limited economic resources.
      Metastatic disease or recurrent lesions not amenable to radical local excision or
      regional radiation have a poor prognosis, and are treated with palliative
      platinum-based chemotherapy. There are few effective therapeutic options for
      patients who progressed after first-line chemotherapy. Future advances in the
      treatment of metastatic or recurrent disease may rely on more effective and
      better-tolerated therapies, and molecularly driven targeted agents could
      represent an attractive option. Inhibition of tumor angiogenesis and epidermal
      growth factor receptor directed therapies have focused the most recent clinical
      research efforts. A thorough molecular characterization of cervical cancer
      remains crucial for a rationale implementation of targeted agents and companion
      biomarkers. Alternative clinical trial designs may also be necessary to optimize
      the clinical development of new drugs for metastatic cervical cancer.

PMID- 22883214
TI  - Transient defects of mitotic spindle geometry and chromosome segregation errors.
AB  - Assembly of a bipolar mitotic spindle is essential to ensure accurate chromosome
      segregation and prevent aneuploidy, and severe mitotic spindle defects are
      typically associated with cell death. Recent studies have shown that mitotic
      spindles with initial geometric defects can undergo specific rearrangements so
      the cell can complete mitosis with a bipolar spindle and undergo bipolar
      chromosome segregation, thus preventing the risk of cell death associated with
      abnormal spindle structure. Although this may appear as an advantageous strategy,
      transient defects in spindle geometry may be even more threatening to a cell
      population or organism than permanent spindle defects. Indeed, transient spindle
      geometry defects cause high rates of chromosome mis-segregation and aneuploidy.
      In this review, we summarize our current knowledge on two specific types of
      transient spindle geometry defects (transient multipolarity and incomplete
      spindle pole separation) and describe how these mechanisms cause chromosome mis
      segregation and aneuploidy. Finally, we discuss how these transient spindle
      defects may specifically contribute to the chromosomal instability observed in
      cancer cells.

PMID- 22883216
TI  - Community-acquired respiratory viruses and co-infection among patients of Ontario
      sentinel practices, April 2009 to February 2010.
AB  - BACKGROUND: Respiratory viruses are known to cocirculate but this has not been
      described in detail during an influenza pandemic. OBJECTIVES: To describe
      respiratory viruses, including co-infection and associated attributes such as
      age, sex or comorbidity, in patients presenting with influenza-like illness to a
      community sentinel network, during the pandemic A(H1N1)pdm09 in Ontario, Canada.
      METHODS: Respiratory samples and epidemiologic details were collected from 1018
      patients with influenza-like illness as part of respiratory virus surveillance
      and a multiprovincial case-control study of influenza vaccine effectiveness.
      RESULTS: At least one virus was detected in 668 (65.6%) of 1018 samples; 512
      (50.3%) had single infections and 156 (15.3%) co-infections. Of single
      infections, the most common viruses were influenza A in 304 (59.4%) samples of
      which 275 (90.5%) were influenza A(H1N1)pdm09, and enterovirus/rhinovirus in 149
      (29.1%) samples. The most common co-infections were influenza A and respiratory
      syncytial virus B, and influenza A and enterovirus/rhinovirus. In multinomial
      logistic regression analyses adjusted for age, sex, comorbidity, and timeliness
      of sample collection, single infection was less often detected in the elderly and
      co-infection more often in patients <30 years of age. Co-infection, but not
      single infection, was more likely detected in patients who had a sample collected
      within 2 days of symptom onset as compared to 3-7 days. CONCLUSIONS: Respiratory
      viral co-infections are commonly detected when using molecular techniques. Early
      sample collection increases likelihood of detection of co-infection. Further
      studies are needed to better understand the clinical significance of viral co
      infection.

PMID- 22883217
TI  - Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic
      encephalopathy.
AB  - BACKGROUND: Recent observations suggest that inflammatory response may be
      important in the pathogenesis of hepatic encephalopathy. The aim of the study was
      to measure arterial ammonia, tumour necrosis factor-alpha, Interleukin-6,
      Interleukin-18, and serum endotoxin levels and their correlation with different
      grades of hepatic encephalopathy. METHODS: 120 patients with cirrhosis were
      enrolled: 20 patients each of cirrhosis with grades I, II, III and IV hepatic
      encephalopathy, cirrhosis with and without minimal hepatic encephalopathy and
      healthy controls were tested for arterial ammonia, tumour necrosis factor-alpha,
      Interleukin-6, Interleukin-18 and serum endotoxin levels. RESULTS: Median
      arterial ammonia, tumour necrosis factor-alpha, Interleukin-6, Interleukin-18 and
      serum endotoxin levels were significantly higher in patient with hepatic
      encephalopathy and minimal hepatic encephalopathy as compared to patients without
      minimal hepatic encephalopathy and healthy controls. Arterial ammonia (r = 0.72,
      p = 0.03), tumour necrosis factor alpha (r = 0.87, p = 0.02), Interleukin-6 (r =
      0.50, p = 0.05), Interleukin-18 (r = 0.76, p = 0.02) and serum endotoxin (r =
      0.91, p = 0.01) correlated with higher grades of hepatic encephalopathy.
      CONCLUSION: In hepatic encephalopathy arterial ammonia, inflammatory mediators,
      and serum endotoxin are elevated and correlate with encephalopathy grade.

PMID- 22883218
TI  - Effects of bile duct ligation and cholic acid treatment on fatty liver in two rat
      models of non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease, one of the most prevalent liver
      disorders in Western countries, is characterized by hepatic accumulation of
      triglycerides. Bile acids have long been known to affect triglyceride homeostasis
      through a not completely understood mechanism. AIM: To analyse the effects of two
      different manipulations of bile acid circulation on non-alcoholic fatty liver
      disease. METHODS: Two animal models of non-alcoholic fatty liver disease were
      developed by either feeding rats with a choline deficient or with a high fat
      diet. After 4 weeks, rats were randomized to undergo either bile duct ligation,
      sham operation or cholic acid administration. RESULTS: During cholestasis there
      was an increased CYP7A1 expression, the rate limiting enzyme in bile acid
      synthesis, and a reduction of hepatic concentration of oxysterols, ligands of the
      liver X receptors. Target genes of the liver X receptors, involved in fatty acid
      and triglyceride synthesis, were down-regulated in association with decreased
      hepatic triglyceride content and improvement of fatty liver. Administration of
      cholic acid, ligand of farnesoid X receptor, also had a beneficial effect on
      fatty liver in rats on choline deficient diet. CONCLUSION: These results indicate
      that pharmacological approaches increasing the expression of CYP7A1 or
      stimulating farnesoid X receptor pathway could represent a promising treatment
      for non-alcoholic fatty liver disease.

PMID- 22883219
TI  - 18F-fluorodeoxyglucose positron emission tomography after definitive
      chemoradiotherapy in patients with oesophageal carcinoma.
AB  - BACKGROUND: The purpose of the study was to investigate the value of 18F
      fluorodeoxyglucose-positron emission tomography performed after definitive
      chemoradiotherapy in patients with locally advanced oesophageal carcinoma.
      METHODS: Forty consecutive patients underwent 18F-fluorodeoxyglucose-positron
      emission tomography at baseline and after chemoradiotherapy completion.
      Assessment of the clinical complete response to chemoradiotherapy included
      oesophagoscopy plus biopsies and computed tomography scan. Cox regression
      analysis was used to develop the univariate and multivariate models describing
      the association of the independent variables with survival and local control.
      RESULTS: A clinical complete response and 18F-fluorodeoxyglucose-positron
      emission tomography response were present in 29 patients (72.5%) and 13 patients
      (32.5%), respectively. A combined response was observed in 11 patients (27.5%).
      During follow-up, a local failure was detected in 27.2% of patients with 18F
      fluorodeoxyglucose-positron emission tomography response versus 33.3% in non
      responders (p=.9). In multivariate analysis, clinical complete response (HR 5.77,
      p=.009) and 18F-fluorodeoxyglucose-positron emission tomography response (HR
      6.27, p=.031) were identified as independent prognostic factors of overall
      survival. CONCLUSION: In patients treated for an esophageal cancer, the present
      study suggested that 18F-fluorodeoxyglucose-positron emission tomography after
      chemoradiotherapy completion was an independent prognostic factor of overall
      survival without significant impact on local recurrence prediction.

PMID- 22883221
TI  - Bedside lung ultrasound in the critically ill patient with pulmonary pathology:
      different diagnoses with comparable chest X-ray opacification.
AB  - The differential diagnosis and treatment of opacifications on the chest X-ray in
      critically ill patients may be challenging. This holds in particular the patient
      that suffers from respiratory failure with hemodynamic instability. Opacification
      in the chest X-ray could be the result of hematothorax, pleural effusion,
      atelectasis, or consolidation. Physical examination of such patients may not
      always indicate what the cause of the opacification is and thus may not always
      help indicate the correct therapeutic approach. In such cases, bedside ultrasound
      may be very helpful. We present two cases with similar chest X-ray opacifications
      but different diagnoses established with the help of a bedside lung ultrasound.
      There is documented accuracy of ultrasound in differentiating pleural effusions
      from consolidation. Ultrasound is safe and may be an alternative for computed
      tomography scan in a hemodynamically or respiratory unstable intensive care
      patient.

PMID- 22883220
TI  - ApoE isoform-dependent deficits in extinction of contextual fear conditioning.
AB  - The three major human apoE isoforms (apoE2, apoE3 and apoE4) are encoded by
      distinct alleles (epsilon2, epsilon3 and epsilon4). Compared with epsilon3,
      epsilon4 is associated with increased risk to develop Alzheimer's disease (AD),
      cognitive impairments in Parkinson's disease (PD), and other conditions. In
      contrast, a recent study indicated an increased susceptibility to the recurring
      and re-experiencing symptom cluster of Post-Traumatic Stress Disorder (PTSD), as
      well as related memory impairments, in patients carrying at least one epsilon2
      allele. Contextual fear conditioning and extinction are used in human and animal
      models to study this symptom cluster. In this study, acquisition (day 1,
      training), consolidation (day 2, first day of re-exposure) and extinction (days 2
      5) of conditioned contextual fear in human apoE2, apoE3 and apoE4 targeted
      replacement and C57BL/6J wild-type (WT) mice was investigated. Male and female
      apoE2 showed acquisition and retrieval of conditioned fear, but failed to exhibit
      extinction. In contrast, WT, apoE3 and apoE4 mice showed extinction. While apoE2
      mice exhibited lower freezing in response to the context on day 2 than apoE3 and
      apoE4 mice, this cannot explain their extinction deficit as WT mice exhibited
      similar freezing levels as apoE2 mice on day 2 but still exhibited extinction.
      Elevating freezing through extended training preserved extinction in controls,
      but failed to ameliorate extinction deficits in apoE2 animals. These data along
      with clinical data showing an association of apoE2 with susceptibility to
      specific symptom clusters in PTSD supports an important role for apoE isoform in
      the extinction of conditioned fear.

PMID- 22883222
TI  - Intragraft CD11b(+) IDO(+) cells mediate cardiac allograft tolerance by ECDI
      fixed donor splenocyte infusions.
AB  - We have previously shown that pre- and post-transplant infusions of donor
      splenocytes treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI
      SPs) provide permanent donor-specific protection of islet allografts. The
      efficacy of donor ECDI-SPs in protecting vascularized cardiac allografts and
      mechanism(s) of protection are unknown. In this study, we show that infusions of
      ECDI-SPs significantly prolong cardiac allograft survival concomitant with an
      impressive accumulation of CD11b(+) IDO(+)  cells in the cardiac allograft, and
      that the presence of this population is dependent on Gr1(+)  cells. Consequently,
      depletion of Gr1(+)  cells or inhibition of indoleamine 2,3 dioxygenase (IDO)
      activity abrogates graft protection by ECDI-SPs infusions. In addition, T cells
      from ECDI-SPs treated recipients secrete high levels of interleukin 10 and
      interleukin 13 upon in vitro restimulation, which are also dampened in recipients
      treated with the IDO inhibitor. Furthermore, combination of donor ECDI-SPs with a
      short course of rapamycin provides indefinite cardiac allograft survival in 100%
      of the recipients. These findings reveal a novel mechanism of donor ECDI-SPs in
      inducing cardiac transplant tolerance and provide several targets that are
      amenable to therapeutic manipulations for tolerance induction for cardiac
      transplantation.

PMID- 22883225
TI  - TXNIP switches tracks toward a terminal UPR.
AB  - During the progression of diabetes, crosstalk between ER stress and inflammation
      controls islet cell fate. In this issue, Lerner et al. (2012) and Oslowski et al.
      (2012) discover that thioredoxin-interacting protein (TXNIP) is a regulatory
      switch connecting the terminal unfolded protein response (UPR) and NLRP3
      inflammasome to mediate beta cell death.

PMID- 22883224
TI  - Markers of hypercoagulability in CAD patients. Effects of single aspirin and
      clopidogrel treatment.
AB  - BACKGROUND: Cardiovascular disease with disturbances in the haemostatic system,
      might lead to thrombotic complications with clinical manifestations like acute
      myocardial infarction (AMI) and stroke. Activation of the coagulation cascade
      with subsequent increased thrombin generation, characterizes a prothrombotic
      phenotype. In the present study we investigated whether prothrombotic markers
      were associated with risk factors and clinical subgroups in a cohort of patients
      with angiographically verified coronary artery disease (CAD). The patients were
      randomized to long-term treatment with the antiplatelet drugs aspirin or
      clopidogrel, and we further investigated the effect on hypercoagulability of such
      treatment for 1 year, of which limited data exists. METHODS: Venous blood samples
      were collected in fasting condition between 08:00 and 10:30 am, at baseline when
      all patients were on aspirin therapy (n = 1001) and in 276 patients after 1 year
      follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by
      prothrombin fragment 1 + 2 (F1+2) and D-dimer, and the endogenous thrombin
      potentiale (ETP) in the calibrated automated thrombogram (CAT) assay,
      representing ex vivo thrombin generation. In addition soluble tissue factor (sTF)
      and free- and total tissue factor pathway inhibitor (TFPI) were measured.
      RESULTS: We found age to be significantly associated with F1+2 and D-dimer (beta
      = 0.229 and beta =0.417 respectively, p <0.001, both). Otherwise, only weak
      associations were found. F1+2 and D-dimer were higher in women compared to men (p
      <0.001 and p = 0.033, respectively). Smokers had elevated levels of ETP compared
      to non-smokers (p = 0.014). Additionally, patients on renin-angiotensin system
      (RAS) inhibition showed significantly higher levels of F1+2, compared to non
      users (p = 0.013). Both aspirin and clopidogrel reduced levels of ETP after 12
      months intervention (p = 0.003 and p <0.001, respectively) and the levels of F1+2
      were significantly more reduced on aspirin compared to clopidogrel (p = 0.023).
      CONCLUSIONS: In the present population of stable CAD, we could demonstrate a more
      hypercoagulable profile among women, smokers and patients on RAS medication,
      assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term
      antiplatelet treatment with aspirin alone seems to attenuate thrombin generation
      to a greater extent than with clopidogrel alone. The study is registered at
      http://www.clinicaltrials.gov: NCT00222261.

PMID- 22883226
TI  - Nutropioids, hedonism in the gut?
AB  - The opioid system plays a pivotal role in how our brain regulates hedonic
      components of ingestive behavior. Duraffourd et al. (2012) add the gut to this
      opioid landscape, demonstrating direct activation of periportal MU-opioid
      receptors by food-derived opioid peptides (nutropioids), and a gut-brain feedback
      spiral that culminates in enhanced satiety.

PMID- 22883227
TI  - Nrf2 orchestrates fuel partitioning for cell proliferation.
AB  - Why upregulation of the transcription factor Nrf2 increases tumor cell
      proliferation is unclear. Mitsuishi et al. (2012) now provide evidence that Nrf2
      augments purine nucleotide synthesis, thus supporting tissue hypertrophy. This
      change in cellular metabolism requires loss of Nrf2 repression by Keap1 as well
      as costimulation via the PI3K-Akt pathway.

PMID- 22883228
TI  - The mitochondrial pyruvate carrier: has it been unearthed at last?
AB  - The mitochondrial pyruvate carrier (MPC) is essential for several major pathways
      of carbohydrate, fat, and amino acid metabolism, yet its molecular identity has
      remained elusive. Two recent papers in Science (Herzig et al., 2012; Bricker et
      al., 2012) implicate three newly identified inner mitochondrial membrane proteins
      as MPC components.

PMID- 22883229
TI  - Selective insulin and leptin resistance in metabolic disorders.
AB  - Obesity represents a major risk factor for the development of insulin and leptin
      resistance, ultimately leading to a pleiotropic spectrum of metabolic
      alterations. However, resistance to both hormones does not uniformly affect all
      target cells and intracellular signaling pathways. In contrast, numerous clinical
      phenotypes arise from selective hormone resistance, leading to inhibition of
      defined intracellular signaling pathways in some tissues, while in other cell
      types hormone action is maintained or even overactivated. Here, we review the
      molecular mechanisms and clinical outcomes resulting from selective insulin and
      leptin resistance, which should ultimately guide future strategies for the
      treatment of obesity-associated diseases.

PMID- 22883230
TI  - High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue
      to promote metabolic dysfunction.
AB  - Adipose tissue plays an important role in storing excess nutrients and preventing
      ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage
      in adipocytes, resulting in the generation of stress signals and the derangement
      of metabolic functions. SIRT1 is an important regulatory sensor of nutrient
      availability in many metabolic tissues. Here we report that SIRT1 functions in
      adipose tissue to protect from inflammation and obesity under normal feeding
      conditions, and to forestall the progression to metabolic dysfunction under
      dietary stress and aging. Genetic ablation of SIRT1 in adipose tissue leads to
      gene expression changes that highly overlap with changes induced by high-fat diet
      in wild-type mice, suggesting that dietary stress signals inhibit the activity of
      SIRT1. Indeed, we show that high-fat diet induces the cleavage of SIRT1 protein
      in adipose tissue by the inflammation-activated caspase-1, providing a link
      between dietary stress and predisposition to metabolic dysfunction.

PMID- 22883231
TI  - DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated
      with obesity.
AB  - DEP domain-containing mTOR-interacting protein (DEPTOR) inhibits the mechanistic
      target of rapamycin (mTOR), but its in vivo functions are unknown. Previous work
      indicates that Deptor is part of the Fob3a quantitative trait locus (QTL) linked
      to obesity/leanness in mice, with Deptor expression being elevated in white
      adipose tissue (WAT) of obese animals. This relation is unexpected, considering
      the positive role of mTOR in adipogenesis. Here, we dissected the Fob3a QTL and
      show that Deptor is the highest-priority candidate promoting WAT expansion in
      this model. Consistently, transgenic mice overexpressing DEPTOR accumulate more
      WAT. Furthermore, in humans, DEPTOR expression in WAT correlates with the degree
      of obesity. We show that DEPTOR is induced by glucocorticoids during adipogenesis
      and that its overexpression promotes, while its suppression blocks, adipogenesis.
      DEPTOR activates the proadipogenic Akt/PKB-PPAR-gamma axis by dampening mTORC1
      mediated feedback inhibition of insulin signaling. These results establish DEPTOR
      as a new regulator of adipogenesis.

PMID- 22883232
TI  - O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by
      modulating PGC-1alpha stability.
AB  - A major cause of hyperglycemia in diabetic patients is inappropriate hepatic
      gluconeogenesis. PGC-1alpha is a master regulator of gluconeogenesis, and its
      activity is controlled by various posttranslational modifications. A small
      portion of glucose metabolizes through the hexosamine biosynthetic pathway, which
      leads to O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic
      and nuclear proteins. Using a proteomic approach, we identified a broad variety
      of proteins associated with O-GlcNAc transferase (OGT), among which host cell
      factor C1 (HCF-1) is highly abundant. HCF-1 recruits OGT to O-GlcNAcylate PGC
      1alpha, and O-GlcNAcylation facilitates the binding of the deubiquitinase BAP1,
      thus protecting PGC-1alpha from degradation and promoting gluconeogenesis.
      Glucose availability modulates gluconeogenesis through the regulation of PGC
      1alpha O-GlcNAcylation and stability by the OGT/HCF-1 complex. Hepatic knockdown
      of OGT and HCF-1 improves glucose homeostasis in diabetic mice. These findings
      define the OGT/HCF-1 complex as a glucose sensor and key regulator of
      gluconeogenesis, shedding light on new strategies for treating diabetes.

PMID- 22883235
TI  - Surface tension of concentrated electrolyte solutions.
AB  - The surface tension sigma of inorganic electrolyte aqueous solutions at a given
      concentration c follows the Hofmeister series. The explanation of this phenomenon
      was sought in the increased adsorption of certain ions due to specific ion
      surface interactions. However, the ion-specific dependence of the activity
      coefficient gamma(+/-) on c also influences sigma, and its contribution to the
      ion-specificity of sigma prevails. Thus, the surface tension of potassium salts
      follows the order sigma(KOH)>sigma(KCl)>sigma(KNO3), which turns out to be a
      direct corollary of the corresponding activity coefficients series:
      gamma(KOH)>gamma(KCl)>gamma(KNO3). In fact, the adsorption of NO(3)(-) at the
      water surface is lower than that of OH(-) and Cl(-)! If the bulk ion-specific
      effects are correctly evaluated, Schmutzer's classical model predicts accurately
      the surface tension of a large number of inorganic salt solutions in a wide
      concentration range, without adjustable parameters. This model accounts for image
      and hydration forces. Comparison with tensiometric data shows that other ion
      surface interactions play a role only in the adsorption of ions of bare radius
      larger than a threshold value of about 1.95 A (e.g. HCOO(-), I(-), SCN(-)).

PMID- 22883233
TI  - IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3
      inflammasome and promote programmed cell death under irremediable ER stress.
AB  - When unfolded proteins accumulate to irremediably high levels within the
      endoplasmic reticulum (ER), intracellular signaling pathways called the unfolded
      protein response (UPR) become hyperactivated to cause programmed cell death. We
      discovered that thioredoxin-interacting protein (TXNIP) is a critical node in
      this "terminal UPR." TXNIP becomes rapidly induced by IRE1alpha, an ER
      bifunctional kinase/endoribonuclease (RNase). Hyperactivated IRE1alpha increases
      TXNIP mRNA stability by reducing levels of a TXNIP destabilizing microRNA, miR
      17. In turn, elevated TXNIP protein activates the NLRP3 inflammasome, causing
      procaspase-1 cleavage and interleukin 1beta (IL-1beta) secretion. Txnip gene
      deletion reduces pancreatic beta cell death during ER stress and suppresses
      diabetes caused by proinsulin misfolding in the Akita mouse. Finally, small
      molecule IRE1alpha RNase inhibitors suppress TXNIP production to block IL-1beta
      secretion. In summary, the IRE1alpha-TXNIP pathway is used in the terminal UPR to
      promote sterile inflammation and programmed cell death and may be targeted to
      develop effective treatments for cell degenerative diseases.

PMID- 22883236
TI  - Fibrinogen conformations and charge in electrolyte solutions derived from DLS and
      dynamic viscosity measurements.
AB  - Hydrodynamic properties of fibrinogen molecules were theoretically calculated.
      Their shape was approximated by the bead model, considering the presence of
      flexible side chains of various length and orientation relative to the main body
      of the molecule. Using the bead model, and the precise many-multipole method of
      solving the Stokes equations, the mobility coefficients for the fibrinogen
      molecule were calculated for arbitrary orientations of the arms whose length was
      varied between 12 and 18 nm. Orientation averaged hydrodynamic radii and
      intrinsic viscosities were also calculated by considering interactions between
      the side arms and the core of the fibrinogen molecule. Whereas the hydrodynamic
      radii changed little with the interaction magnitude, the intrinsic viscosity
      exhibited considerable variation from 30 to 60 for attractive and repulsive
      interactions, respectively. These theoretical results were used for the
      interpretation of experimental data derived from sedimentation and diffusion
      coefficient measurements as well as dynamic viscosity measurements. Optimum
      dimensions of the fibrinogen molecule derived in this way were the following: the
      contour length 84.7 nm, the side arm length 18 nm, and the total volume 470
      nm(3), which gives 16% hydration (by volume). Our calculations enabled one to
      distinguish various conformational states of the fibrinogen molecule, especially
      the expanded conformation, prevailing for pH<4 and lower ionic strength,
      characterized by high intrinsic viscosity of 50 and the hydrodynamic radius of
      10.6 nm. On the other hand, for the physiological condition, that is, pH=7.4 and
      the ionic strength of 0.15M NaCl, the semi-collapsed conformation dominates. It
      is characterized by the average angle equal to <phi>=55 degrees , intrinsic
      viscosity of 35, and the hydrodynamic radius of 10nm. Additionally, the
      interaction energy between the arms and the body of the molecule was predicted to
      be -4 kT units, confirming that they are oppositely charged than the central
      nodule. Results obtained in our work confirm an essential role of the side chains
      responsible for a highly anisotropic charge distribution in the fibrinogen
      molecule. These finding can be exploited to explain anomalous adsorption of
      fibrinogen on various surfaces.

PMID- 22883234
TI  - Thioredoxin-interacting protein mediates ER stress-induced beta cell death
      through initiation of the inflammasome.
AB  - Recent clinical and experimental evidence suggests that endoplasmic reticulum
      (ER) stress contributes to the life-and-death decisions of beta cells during the
      progression of type 1 and type 2 diabetes. Although crosstalk between
      inflammation and ER stress has been suggested to play a significant role in beta
      cell dysfunction and death, a key molecule connecting ER stress to inflammation
      has not been identified. Here we report that thioredoxin-interacting protein
      (TXNIP) is a critical signaling node that links ER stress and inflammation. TXNIP
      is induced by ER stress through the PERK and IRE1 pathways, induces IL-1beta mRNA
      transcription, activates IL-1beta production by the NLRP3 inflammasome, and
      mediates ER stress-mediated beta cell death. Collectively, our results suggest
      that TXNIP is a potential therapeutic target for diabetes and ER stress-related
      human diseases such as Wolfram syndrome.

PMID- 22883237
TI  - Combination of electroreduction with biosorption for enhancement for removal of
      hexavalent chromium.
AB  - Hexavalent chromium is one of the most toxic heavy metals in aqueous solutions.
      It has been well documented that the brown seaweed can be used as a promising
      biosorbent for the sequestration of this heavy metal from wastewater. However,
      the uptake of Cr(VI) is reportedly a rather slower process; the sorption
      equilibrium can only be established after a few days, much slower than a few
      hours for the trivalent chromium ion. In this study, we developed a novel
      technology of electrochemically assisted biosorption (ECAB) system for the
      enhancement of the treatment efficiency. It was found through our study that the
      removal efficiencies of Cr(VI) and total chromium were greatly enhanced by 48.1%
      and 51.3%, respectively, with the application of -1.0 V in the ECAB system. The
      conversion of Cr(III) due to the electroreduction of Cr(VI) and the higher pH due
      to the cathodic H(2) evolution created a favorable condition for the uptake of
      chromium onto the modified seaweed (MSW). The reduction and adsorption of Cr(VI)
      by MSW was proved to play a minor role in the removal. Both direct
      electroreduction and indirect electroreduction by atomic H* contributed to the
      reduction of Cr(VI).

PMID- 22883238
TI  - Adsorption of sodium dodecyl sulfate onto clathrate hydrates in the presence of
      salt.
AB  - This work presents the effect of NaCl on the adsorption of sodium dodecyl sulfate
      (SDS) at the cyclopentane (CP) hydrate-water interface. The adsorption isotherms
      and the SDS solubility in NaCl solutions are obtained using liquid-liquid
      titrations. The solubility data are determined at typical hydrate forming
      temperatures (274-287 K) to ensure that the adsorption isotherms are obtained
      within SDS solubility limits in NaCl solutions. The isotherms show L-S (Langmuir
      Step) type behaviors with 1mM and 10mM NaCl solutions while L type isotherm is
      determined for 25 mM NaCl solutions due to the low SDS solubility in this salt
      concentration. Zeta potentials of CP hydrate particles in the aqueous solutions
      support the shape of the adsorption isotherm with the 1mM NaCl solution. The 1mM
      NaCl case shows the highest SDS adsorption amount among the cases with 0 mM, 10
      mM, and 25 mM NaCl solutions. In this case, the competition for adsorption
      between Cl(-) and DS(-) is not as strong compared to the 10 and 25 mM NaCl cases
      and the presence of Na(+) ions may reduce the repulsion between DS(-) ions, which
      results in a higher adsorption of DS(-) ions and enhanced enclathration.

PMID- 22883239
TI  - Vitamin D status of Irish adults: findings from the National Adult Nutrition
      Survey.
AB  - Previous national nutrition surveys in Irish adults did not include blood
      samples; thus, representative serum 25-hydroxyvitamin D (25(OH)D) data are
      lacking. In the present study, we characterised serum 25(OH)D concentrations in
      Irish adults from the recent National Adult Nutrition Survey, and determined the
      impact of vitamin D supplement use and season on serum 25(OH)D concentrations. Of
      the total representative sample (n 1500, aged 18+ years), blood samples were
      available for 1132 adults. Serum 25(OH)D was measured via immunoassay. Vitamin D
      containing supplement use was assessed by questionnaire and food diary.
      Concentrations of serum 25(OH)D were compared by season and in supplement users
      and non-users. Year-round prevalence rates for serum 25(OH)D concentration < 30,
      < 40, < 50 and < 75 nmol/l were 6.7, 21.9, 40.1 and 75.6 %, respectively (11.1,
      31.1, 55.0 and 84.0 % in winter, respectively). Supplement users had
      significantly higher serum 25(OH)D concentrations compared to non-users. However,
      7.5 % of users had winter serum 25(OH)D < 30 nmol/l. Only 1.3 % had serum 25(OH)D
      concentrations >125 nmol/l. These first nationally representative serum 25(OH)D
      data for Irish adults show that while only 6.7 % had serum 25(OH)D < 30 nmol/l
      (vitamin D deficiency) throughout the year, 40.1 % had levels considered by the
      Institute of Medicine as being inadequate for bone health. These prevalence
      estimates were much higher during winter time. While vitamin D supplement use has
      benefits in terms of vitamin D status, at present rates of usage (17.5 % of Irish
      adults), it will have only very limited impact at a population level. Food-based
      strategies, including fortified foods, need to be explored.

PMID- 22883240
TI  - [Health science research: the role of translation].

PMID- 22883241
TI  - [The doctor Pedro Hispano Portucalense (1205 - 1277)].

PMID- 22883242
TI  - [Evaluation of the performance of three spacers].
AB  - INTRODUCTION: Several aspects are known to influence the drug distribution within
      the low respiratory tract, with particular emphasis on those related to the
      inhalation device. The aim of this work was to assess the performance of three
      spacers in the drug release, and also the quantity of active agent deposited
      inside these devices. MATERIALS AND METHODS: In order to evaluate the behaviour
      of particles in suspension delivered through the Ventilan(r)HFA inhaler coupled
      to three different spacers (Volumatic(r), AeroChamber MAX(r) and NebuChamber(r))
      the Multistage Liquid Impinger (MSLI) was used, according to the Portuguese
      Pharmacopoeia. The mass of salbutamol sulphate deposited on the different
      impinger compartments and inside the spacer was determined by spectrophotometry,
      with the purpose of determining the percentage of cumulative mass for each
      spacer, and then the fine particle fraction. The results were compared
      statistically using a one-way analysis of variance (one-way ANOVA) with a
      Bonferroni post-hoc test. RESULTS: About 40 to 50% of salbutamol sulphate was
      found deposited in the body of the three spacers. This deposition was slightly
      lower for NebuChamber(r) (average +/- standard deviation of 43.8 % +/- 11.6 %),
      in relation to Volumatic(r) (p=0.351) or AeroChamber MAX(r) (p=0.115). The fine
      particle fraction reached values of 28.2 +/- 4.1%, 29.6 +/- 2.4% and 30.9 +/-
      6.7% for Volumatic(r), AeroChamber MAX(r) and NebuChamber(r), respectively.
      CONCLUSION: The spacers showed to have similar efficiencies in the delivery of
      salbutamol sulphate in the last stages, and there was no relation between the
      results and the spacers characteristics such as volume, shape and material.
      Therefore, Volumatic(r) appears to be perfect for hospital use, since its big
      volume does not constitute a disadvantage, and its lower cost, when compared to
      the remaining two spacers, represents an advantage of utmost importance for
      public hospitals.

PMID- 22883243
TI  - [Validation of a nutritional screening tool].
AB  - BACKGROUND: Malnutrition is an imbalance between spending and the need of
      nutrients. The prevalence of hospital malnutrition is increasing according to
      recent studies. Several factors may contribute to the magnitude of the clinical
      manifestations caused by malnutrition, such as etiology and disease's severity,
      duration of nutritional deficit, patient age and co-morbidities. This condition
      can cause increased morbidity and mortality and higher costs for healthcare
      resulting in longer hospital stay. Therefore, the use of a practical nutritional
      screening tool is important to enable early detection of nutritional risk, aiming
      the prevention of weight loss or it continuity, recovery of nutritional status,
      and achieving a better clinical outcome by adopting better nutritional
      interventions. OBJECTIVE: To validate the pre-screening tool for nutritional
      screening upon admission, during the nutritional anamnesis, and during the
      patient's daily visit. METHOD: Cross-sectional study with methodological
      character performed in the emergency room of a public hospital with 196 patients
      of both sexes, hospitalized, with middle age greater than or equal to 18 years.
      Two protocols for the assessment of nutritional risk were applied: the Subjective
      Global Assessment, considered the gold standard, and the Nutrition Pre-screening
      tool, instrument to be validated. The sample was analysed in relation to age,
      gender distribution and results of the PTN and ANSG. RESULTS AND DISCUSSION: 39%
      of the sample consisted of females and 61% for males. The correlation degree
      between the results of the screening methods according to the Kappa coefficient
      was 0.80. The sensitivity and specificity were 96.9% and 80.0% respectively. The
      positive predictive value was 90.65% and negative predictive value of 92.98%.
      This high correlation found, as well as the values for sensitivity, specificity
      and positive and negative predictive values are representative of a substantial
      agreement between the two screening tools. CONCLUSION: Nutrition Pre-screening
      tool is an efficient nutritional protocol; it is fast, convenient and easily
      applied at any time during hospitalization.

PMID- 22883244
TI  - [Sexual issues: a qualitative analysis of the doubts after a spinal cord injury].
AB  - This article presents and discusses the results obtained from 35 Portuguese with
      acquired spinal cord injury who were asked what type of sexual questions would
      like to ask to the health team. The collection of individual data originated
      categories, which emerged from the perceptions of subjects, thus constituting the
      discourse of the group and the conclusion. This study allowed access to the
      meanings that have translated the perceived needs for information on clinical
      aspects, often neglected.

PMID- 22883245
TI  - [Evolution of outpatient antibiotic use in Portugal mainland 2000-2009].
AB  - INTRODUCTION: In the latest years, the increasing resistance to antibiotics has
      become a serious public health issue. The resistance to antimicrobial agents is
      multifactorial although several studies have shown that the large use of
      antibiotics for therapeutical and prophylactic purposes, and particularly their
      misuse, is one factor that contributes most to this problem. AIM: To assess the
      evolution of antibiotic consumption in Portugal, Health Regions and Districts of
      Portugal, from 2000 to 2009. MATERIAL AND METHODS: Descriptive observational
      study using as source of information a database of outpatient antibiotic
      prescription provided by Infarmed, National Authority of Medicines and Health
      Products. Antibiotic consumption is estimated up from medical prescription, and
      expressed in DDD/1000 inhabitants/day (DHD). RESULTS: From 2000 to 2009
      antibiotic total consumption varied between 24,12 DHD and 22,03 DHD, which means
      a decrease by 8,65%. The use of tetracyclines (J01A), cephalosporins (J01D),
      sulphonamides (J01E), quinolones (J01M) and other antibacterials (J01B, J01G and
      J01X) decreased during the aforesaid time period. By contrast, there was an
      increase in the use of the combination penicillin and beta-lactamases inhibitor,
      and macrolides (J01F). Between 2000 and 2009 there was a significant decrease in
      the use of outpatient cephalosporins (- 43,50%). Most notable is the large
      reduction of the use of cephalosporins between 2000 and 2009 (-43.50%) and also
      the decrease in the consumption of quinolones (-15.31%). CONCLUSION: Although
      there has been a decrease in the use of antibiotics in Portugal, their
      consumption is still high. The current study provides information that may be
      useful to regional Health Authorities in order to develop educational activities,
      for the population or health professionals, which can promote the rational use of
      antibiotics.

PMID- 22883247
TI  - [The response of intensive care medicine in situations of multiple victims and
      catastrophe].
AB  - There is a change in attitude regarding critical patients in situations of
      multiple victims and disasters in order to give the better treatment to the
      largest number of patients. Recent large-scale accidents, including terrorist
      attacks and biological warfare as the outbreak of Severe Acute Respiratory
      Syndrome (SARS) in 2002/2003 and pandemic influenza have demonstrated the need
      for an adequate response from Intensive Care Medicine in those contexts. It is
      essential, according to risk analysis, organizing and planning the response of
      the Intensive Care Units in accordance with its strategy to increase the capacity
      of beds in intensive care. It is necessary a permanent preparation of the
      Intensive Care Units to face exceptional situations, giving focus to the training
      of professionals, triage and expansion of Intensive Care Units, emphasizing the
      role of intensivists in these cases.

PMID- 22883246
TI  - [Iodine intake in Portuguese school children].
AB  - OBJECTIVE: The aim of the present study was to evaluate iodine intake in
      portuguese school children in order to inform health authorities of eventual
      measures to be implemented. INTRODUCTION: Iodine is the key element for thyroid
      hormone synthesis and its deficiency even mild, as found in other European
      countries, may have deleterious effects in pregnancy resulting in cognitive
      problems of offsprings. In Portugal there are no recent data on iodine intake in
      schoolchildren. POPULATION AND METHODS: 3680 children aged 6-12 years of both
      sexes, from 78 different schools were studied. Iodine intake was evaluated trough
      urine iodine (UI) determinations using a colorimetic method. RESULTS: The global
      median UI value was 105.5 ug/L; the percentage of children with UI <100 ug/L was
      47.1%, corresponding to 41% of the studied schools. The percentage of values <50
      ug/L was 11.8%. The male gender, the south region of the country and the
      distribution of milk in school were significantly linked with a higher iodine
      elimination. DISCUSSION: Our global results point to a borderline/ mildly
      insufficient iodine intake in the portuguese school population. However 47% of
      the children had UI under 100 ug /L. The comparison of our results with the
      available data from 30 years ago, point to a considerable improvement, due to
      silent prophylaxis. Male gender, geographical area and milk distribution
      influenced positively iodine intake.The importance of milk has been referred in
      numerous papers. CONCLUSIONS: The study of UI in the Portuguese school population
      points to a borderline iodine intake. However, in 47% of children iodine intake
      was inadequate. Compared with data from the eighties, a considerable increase in
      iodine elimination was found. Taking into account the potencial deleterious
      effects of inadequate iodine intake, a global prophylaxis with salt iodization
      has to be considered.

PMID- 22883248
TI  - [Generalization of the results of clinical studies through the analysis of
      subgroups].
AB  - Subgroup analysis in clinical trials are usually performed to define the
      potential heterogeneity of treatment effect in relation with the baseline risk,
      physiopathology, practical application of therapy or the under-utilization in
      clinical practice of effective interventions due to uncertainties of its
      benefit/risk ratio. When appropriately planned, subgroup analysis are a valid
      methodology the define benefits in subgroups of patients, thus providing good
      quality evidence to support clinical decision making. However, in order to be
      correct, subgroup analysis should be defined a priori, done in small numbers,
      should be fully reported and, most important, must endure statistical tests for
      interaction. In this paper we present an example of the treatment of post
      menopausal osteoporosis, in which the benefits of an intervention (the higher the
      fracture risk is, the better the benefit is) with a specific agent (bazedoxifene)
      was only disclosed after a post-hoc analysis of the initial global trial sample.

PMID- 22883249
TI  - [Necrotizing pneumonia - a rare complication].
AB  - Necrotizing pneumonia is a rare complication of community-acquired pneumonia
      associated with destruction of the lung tissue during the infection and rise of
      necrotic foci in consolidated areas. Staphylococcus aureus, Streptococcus
      pyogenes, Nocardia, Klebsiella pneumoniae and Streptococcus pneumoniae are the
      most common causative agents. Risk factors for developing necrotizing pneumonia
      include smoking, alcoholism, old age, diabetes mellitus, chronic lung diseases or
      liver disease. Diagnosis of necrotizing pneumonia requires supportive care, use
      of broad-spectrum antibiotics and monitoring for sepsis and respiratory failure.
      Hemoptysis, abscess, empyema and gangrene are possible complications and surgical
      intervention may be required. The authors present a clinical case of pneumococcal
      necrotizing pneumonia in a patient without important risk factors and favourable
      progression with medical therapy. In this regard, a brief bibliographic review
      about this pathology is also made.

PMID- 22883250
TI  - [Spontaneous ileopsoas hematoma: a rare and lethal complication of liver
      cirrhosis].
AB  - Spontaneous ileopsoas hematoma is a rare and potentially lethal complication of
      liver cirrhosis, with exceptional mention in medical literature. In this article
      we present a clinical case diagnosed in a patient with alcoholic liver cirrhosis.

PMID- 22883251
TI  - Extrapulmonary tuberculosis.

PMID- 22883252
TI  - [Spontaneous interlobar hemopneumothorax].

PMID- 22883253
TI  - [Club drugs].

PMID- 22883254
TI  - The mechanisms that associate community social capital with post-disaster mental
      health: a multilevel model.
AB  - Many scholars have advocated that the time has come to provide empirical evidence
      of the mechanisms that associate community social capital with individual
      disaster mental health. For this purpose we conducted a study (n = 232) one year
      after a flood (2008) in Morpeth, a rural town in northern England. We selected
      posttraumatic stress as an indicator of disaster mental health. Our multilevel
      model shows that high community social capital is indirectly salutary for
      individual posttraumatic stress. In particular, in communities (defined as
      postcode areas) with high structural social capital, the results suggest that
      individuals confide in the social context (high cognitive social capital) to
      address disaster-related demands (high collective efficacy), and employ less
      individual psychosocial resources (i.e. coping strategies and social support).
      This "conservation of individual psychosocial resources" in a salutary social
      context decreases the association between the appraisal of the disaster and
      posttraumatic stress. As a result of this mechanism, individuals suffer less from
      posttraumatic stress in communities with high social capital. These findings
      provide new insights how intervention policies aimed at strengthening both
      objective and subjective dimensions of social capital may reduce post-disaster
      mental health.

PMID- 22883255
TI  - Hidden costs: the direct and indirect impact of user fees on access to malaria
      treatment and primary care in Mali.
AB  - About 20 years after initial calls for the introduction of user fees in health
      systems in sub-Saharan Africa, a growing coalition is advocating for their
      removal. Several African countries have abolished user fees for health care for
      some or all of their citizens. However, fee-for-service health care delivery
      remains a primary health care funding model in many countries in sub-Saharan
      Africa. Although the impact of user fees on utilization of health services and
      household finances has been studied extensively, further research is needed to
      characterize the multi-faceted health and social problems associated with
      charging user fees. This ethnographic study aims to identify consequences of user
      fees on gender inequality, food insecurity, and household decision-making for a
      group of women living in poverty. Ethnographic life history interviews were
      conducted with 24 women in Yirimadjo, Mali in 2007. Purposive sampling selected
      participants across a broad socio-economic spectrum. Semi-structured interviews
      addressed participants' past medical history, socio-economic status, social and
      family history, and access to health care. Interview transcripts were coded using
      the guiding analytical framework of structural violence. Interviews revealed that
      user fees for health care not only decreased utilization of health services, but
      also resulted in delayed presentation for care, incomplete or inadequate care,
      compromised food security and household financial security, and reduced agency
      for women in health care decision making. The effects of user fees were amplified
      by conditions of poverty, as well as gender and health inequality; user fees in
      turn reinforced the inequalities created by those very conditions. The
      qualitative data reveal multi-faceted health and socioeconomic effects of user
      fees, and illustrate that user fees for health care may impact quality of care,
      health outcomes, food insecurity, and gender inequality, in addition to impacting
      health care utilization and household finances. As many countries consider user
      fee abolition policies, these findings indicate the need to create a broader
      evaluation framework-one that can measure the health and socioeconomic impacts of
      user fee polices and of their removal.

PMID- 22883256
TI  - Do workers underreport morbidity? The accuracy of self-reports of chronic
      conditions.
AB  - We use matched Danish health survey and register data to investigate
      discrepancies between register-based diagnoses and self-reported morbidity. We
      hypothesize that false negatives (medical diagnoses existing in the register but
      not reported in the survey) arise partly because individuals fear career
      repercussions of being discovered suffering a chronic or severe illness that
      potentially lowers productivity. We find evidence of substantial underreporting,
      which is indeed systematically higher for individuals in the labor market.

PMID- 22883257
TI  - [Incidence and mortality of liver cancer in China: an analysis on data from the
      National Registration System between 2003 and 2007].
AB  - OBJECTIVE: To describe and analyze the characteristics and trend of liver cancer,
      through data gathered from the Cancer Registry System, in China. METHODS: Annual
      registration data on cancer incidents and deaths of 2003 - 2007, from 32 cancer
      registries were employed. Crude rates of incidence and mortality, and age
      standardized rates by the China population (ASRc) and the world population (ASRw)
      were calculated. Incidence and mortality rates by age, gender, and by area (urban
      or rural) were analyzed, and comparison was made internationally, based upon data
      from the GLOBOCAN 2008. RESULTS: The total person-years of 2003 - 2007 observed
      from the 32 cancer registries were 255 430 909, in which 197 651 428 from the
      urban areas, and 57 779 481 from the rural areas. A total of 68 146 incident
      cases with liver cancer were reported, which accounted for 10.03% (ranked second)
      of all the registered cases with cancers, with the average annual incidence as
      26.68 per 100 000 (39.42 in males, 13.63 in females). ASRc and ASRw were 13.29
      per 100 000 and 17.45 per 100 000, respectively. Sex ratios for incidence and
      mortality were 2.89:1 and 2.72:1, respectively. Incidence rates were 23.91 per
      100 000 in urban areas, and 36.15 per 100 000 in rural areas. For mortality
      rates, they were 22.39 per 100 000 in urban areas and 34.05 per 100 000 in rural
      areas, respectively. Relative greater differences could be seen amongst these
      registries. The incidence rates were 10.15 - 33.85 per 100 000 in the urban
      areas, and 11.83 - 78.59 per 100 000 in the rural areas. For mortality rates,
      they were 13.99 - 28.45 per 100 000 in urban areas, and 11.02 - 71.99 per 100 000
      in rural areas. According to data from the 184 cancer registries through GLOBOCAN
      2008, liver cancer incidence in China was ranked the 5th in males, and 6th in
      females while mortality was ranked 2nd in males, and 5th in females. CONCLUSION:
      Liver cancer had been the second most leading malignancy, following lung cancer,
      with annual incidents and death cases around 360 000 and 350 000, respectively
      and the figures seemed to be increasing. Nationwide monitoring and research
      programs on liver cancer should be emphasized.

PMID- 22883258
TI  - [Estimation and prediction of incidence, mortality and prevalence on liver
      cancer, in 2008, China].
AB  - OBJECTIVE: To estimate the incidence, mortality and 5-year prevalence rates of
      liver cancer in 2008, China. METHODS: Data from both 36 cancer registries and the
      Third National Death Survey in China (2004 - 2005) were used to estimate the
      incidence, mortality and 5-year prevalence of liver cancer in 2008 in the country
      by using the mathematical models to predict the liver cancer incidence and
      mortality in the next 20 years. RESULTS: In 2008, the incident cases of liver
      cancer was 402 208 (14.3% of the total cancers) and the number of deaths from
      liver cancer was 372 079 (19.0% of the total cancers). The incidence rate was
      25.7/100 000, ranking the third among all cancers. The mortality rate was
      23.7/100 000, ranking the second among all the cancers. The 5-year prevalence of
      liver cancer was 296 082 (6.4% of the total cancers) with the proportion as 27.7/
      100 000, ranking the sixth among all the cancers. 72.8% of the liver cancer cases
      appeared in men and the sex ratio of male to female was 2.7:1. In terms of deaths
      due to liver cancer, 74.3% of them occurred in men, with sex ratio of male to
      female as 2.9:1. At any age group, the incidence and mortality of liver cancer
      among males were higher than those of females. Liver cancer happened more
      frequently among people older than 40 years of age, particularly among males.
      Data under our prediction showed that the incidence and mortality of liver cancer
      in China would gradually increase in the next 20 years. CONCLUSION: Liver cancer
      is one of the most important public health issues in China. Both incidence and
      mortality of liver cancer have been increasing in China. The key populations for
      liver cancer prevention and control programs should be those who were older than
      40-year-old, particularly on men.

PMID- 22883259
TI  - [Under-5-mortality rate and causes of death in China, 2000 to 2010].
AB  - OBJECTIVE: To assess the changes and the leading cause of deaths for children
      under 5 years old, in China, during 2000 - 2010, with the aim of evaluation on
      the progress in achieving the relative goal set by "National Program of Action
      for Child Development in China (2001 - 2010)", and understanding the related
      challenges. METHODS: Data used in this study were collected from the population
      based National Maternal and Child's Health Surveillance Network of China. Infant
      Mortality Rate (IMR), Under-5-mortality rate (U5MR) and the leading cause of
      deaths for under-5 children were analyzed. RESULTS: Nationwide IMR and U5MR in
      2010 dropped by 59.3% and 58.7% respectively, compared to that in 2000. Decreases
      by 50.8% and 47.1% in IMR and U5MR were observed in urban areas, and 56.5% and
      56.0% in rural areas during this period. Compared with data from 2000, the
      leading causes-specific U5MR in 2010 had significantly declined. The top 5
      leading causes of death in 2010 were premature birth/low birth weight, pneumonia,
      birth asphyxia, congenital heart disease and accidental suffocation, but were
      different in urban and rural areas. In 2010, both IMR and U5MR from the rural
      areas were 2.8-folds than that of the urban areas. In addition, IMRs in the
      Middle and Western parts of China were 1.5 and 2.3-folds respectively of that in
      the East, and U5MR in Middle and West was 1.5 and 2.2-folds respectively of that
      in East. CONCLUSION: IMR, U5MR and the leading causes specific mortality rate in
      China declined remarkably from 2000 to 2010, and the goal set by "National
      Program of Action for Child Development in China (2001 - 2010)" had been
      successfully achieved. However, the disparity on child's health in regions and in
      urban or rural areas, still remained a challenge.

PMID- 22883260
TI  - [Characteristics and stability of surveillance data on respiratory syndrome,
      during the Shanghai World Expo in Pudong New District].
AB  - OBJECTIVE: To reveal the characteristics and stability of the system through the
      analyzing the surveillance data of respiratory-feverous syndrome via the
      syndromic surveillance system which was established during the Shanghai World
      Expo in Pudong New District and provide references for the development and
      operation optimization on this Mass Gatherings Surveillance Systems. METHODS:
      Data used was from the surveillance data of respiratory-feverous syndrome
      collected from Pudong New District Syndromic Surveillance System, through May 1
      to October 31, 2010. On the basis of description of data characteristics,
      correlation analyses were conducted, when compared to the surveillance data of
      respiratory-feverous syndrome and Pudong influenza-like illness (ILI) used as
      reference. Comparison of variances on the surveillance data and the report lag
      time of the earlier and later surveillance periods were also carried out to
      evaluate the quality and stability of data. RESULTS: Reports on the respiratory
      feverous syndrome showed a peak in late September with day-of-week effects and
      holiday effects. Correlation between respiratory-feverous syndrome and ILI was
      the strongest in the same day (r = 0.596, P < 0.05). In the earlier surveillance
      period from 2010-05-01 to 2010-07-31, the correlation between respiratory
      feverous syndrome and ILI was not obvious (r = -0.058, P > 0.05); however, the
      two-time series showed consistent trend with the correlation coefficient as 0.798
      (P < 0.05), in the later period from 2010-08-01 to 2010-10-31. In addition,
      variability of the surveillance data on respiratory-feverous syndrome was less in
      the later period than in the earlier one, with quality of the report on related
      data better in the later period. Analyses on the correlations of reference
      sequence, variability and quality of report indicated that the stability of the
      later surveillance period was better than the earlier one. CONCLUSION: Only with
      the operation of syndromic surveillance system for a certain period of time,
      could data in the system maintain stability. Surveillance data showed both day-of
      week effects and holiday effects, suggesting that there was a need to choose
      early warning models with short baseline data.

PMID- 22883261
TI  - [Epidemiological survey on lipid levels in adults with Han, Uygur and Kazakh
      ethnicities from Xinjiang, China].
AB  - OBJECTIVE: To investigate the prevalence rates of triglyceride, total
      cholesterol, high density lipoprotein cholesterol, low density lipoprotein
      cholesterol in Han, Uygur and Kazakh populations aged over 35 years, in Xinjiang
      area. METHODS: A four-stage randomly selected samples were used to analyze the
      prevalence rates of lipid levels in different nationalities, ages, sexes based on
      data from 7 areas in Xinjiang. RESULTS: (1) TG levels in Xinjiang appeared to be
      the highest in Han and lowest in Kazakh ethnicities with the means as (1.72 +/-
      1.45) mmol/L, (1.21 +/- 0.93) mmol/L (F = 209.272, P = 0.000) respectively. The
      highest TC levels were seen in Kazakh with the lowest seen in Uygur, with means
      as (4.78 +/- 1.16) mmol/L, (4.37 +/- 1.13) mmol/L (F = 168.796, P = 0.000)
      respectively. Both HDL-C and LDL-C levels in Kazakh were the highest but remained
      the same level in Han and Uygur. (2) The value of TG reached the peak at age 45
      to 54 in Han and Uygur, and then descending along with ageing. The overall TC
      level increased along with age but the HDL-C level generally declined with
      ageing. The LDL-C level showed a waving distribution along with the increase of
      age. (3) The TG levels were seen higher in men than in women among Han, Uygur and
      Kazakh but the TC levels of Han and Uygur were lower in men than in women. Both
      HDL-C and LDL-C levels were also lower in Han and Kazakh males than in females.
      (4) The prevalence rates of abnormalities were 35.12%, 32.57% and 16.44% on TG;
      27.83%, 17.05% and 33.43% on TC; 32.68%, 31.73% and 28.72% HDL-C; 36.95%, 37.02%
      and 38.00% on LDL-C, respectively. CONCLUSION: People with Han and Uygur
      ethnicities in Xinjiang region had high TG, but low HDL-C distribution of blood
      lipids while the Kazakh had low TG, high TC, high HDL-C, high LDL-C blood lipids
      distribution. The distributions of TG levels were different in age, nationality
      and sex, except the distribution of LDL-C levels. More attention should be paid
      to the young men of Han and Uygur on prevention of dyslipidemia, in Xinjiang.

PMID- 22883262
TI  - [Influence of different dietary patterns on bone mineral density and body mass
      index of college freshmen in urban and rural areas of China].
AB  - OBJECTIVE: To find out the differences of dietary patterns among freshmen coming
      from urban and rural areas that might have influenced their bone mineral density
      and body mass index (BMI). METHODS: With stratified random sampling method,
      dietary patterns and their bone mineral density, BMI of 1319 freshmen were
      studied. RESULTS: (1) The ratios of urban freshmen who chose "western food"
      pattern (chi(2) = 31.548, P = 0.000; chi(2) = 13.068, P = 0.001), "animal food"
      pattern (chi(2) = 8.279, P = 0.016; chi(2) = 41.137, P = 0.000) or "calcium food"
      pattern (chi(2) = 37.254, P = 0.000; chi(2) = 15.651, P = 0.000) were higher than
      that of rural freshmen, and the ratios of rural freshmen who chose "Chinese
      traditional" pattern (chi(2) = 36.194, P = 0.000; chi(2) = 25.936, P = 0.000)
      were higher than that of urban freshmen. (2) The average height, weight, BMI,
      speed of sound (SOS) of male freshmen from rural areas were lower than that from
      the city and the differences were statistically significant (P < 0.05). Among
      those female freshmen, only height and weight were significantly different (P <
      0.05). (3) In both rural and urban freshmen, the factor scores of "western food"
      pattern had a positive correlation with BMI, with the correlation coefficients as
      0.187, 0.192, 0.551, 0.465 (P < 0.001). The factor scores of "calcium food"
      pattern were positively related to bone mineral density (SOS values) with
      correlation coefficients as 0.680, 0.342, 0.841, 0.786, P < 0.001 respectively.
      The factor scores on "Chinese traditional" pattern were negatively correlated
      with BMI, with correlation coefficients as -0.223, -0.093 (P < 0.05) which were
      positively related to bone mineral density (SOS values) in both rural and urban
      male freshmen, with correlation coefficients as 0.905, 0.711 (P < 0.001).
      CONCLUSION: Different dietary patterns chosen by urban and rural freshmen had a
      significant impact on both bone mineral density and BMI.

PMID- 22883263
TI  - [Study on the references regarding height and prevalence of stunting among
      children and adolescents aged 7 to 18 years of Chinese Han ethnicity].
AB  - OBJECTIVE: To develop the reference on height among children and adolescents aged
      7 to 18 years of Chinese Han ethnicity in different administrative districts of
      China and to use this height reference for screening stunting. Results from the
      national screening program were compared with the WHO references. METHODS: Data
      from the Chinese National Survey on Students Constitution and Health in 2005 was
      used to develop the height references through LMS method. RESULTS: Differences
      among the references on height for children and adolescents in different
      districts (I-IV) were remarkable. The highest was seen in the Second Districts
      while the lowest was seen in the First Districts among those at the age of 18,
      with differences as 3.18 cm for boys and 2.92 cm for girls. The heights from the
      inland were shorter than that of the WHO references, with the differences ranging
      from 0.31 cm to 5.07 cm for boys, and from 0.98 cm to 4.22 cm for girls. The
      prevalence rates of stunting were 2.22%, 2.29%, 5.25%, respectively according to
      local references, national references and the WHO references. CONCLUSION:
      Universal height references from the whole nation could not discriminate the
      variations caused by geographic conditions and hereditary factors related to
      socio-economic situations. Height references should be developed locally, to
      evaluate height levels of the areas.

PMID- 22883264
TI  - [Applicability of self-rated pubertal development scale among urban Chinese
      adolescents].
AB  - OBJECTIVE: To explore the applicability of pubertal development scale in
      estimating sexual maturation among urban Chinese adolescents. METHODS: A cross
      sectional survey was conducted among 2562 students of 4(th) to 12(th) grade in
      Shanghai, selected by stratified cluster sampling method. Self-reported pubertal
      maturation level was obtained by Pubertal Development Scale (PDS). Meanwhile,
      visual depiction of Tanner stages of breast, genital and pubic hair development
      were rated by a trained rater of the same gender. RESULTS: In 2562 students, the
      correlation between self-reported PDS and assessment from the raters were
      substantial, both in boys and girls (Pearson's correlation coefficients: 0.822
      and 0.814, respectively). The overall agreement of pubertal development stages
      based on PDS and the rater's assessment were 35.24% and 51.42% for boys and
      girls, respectively, with Kendall's correlation coefficients as 0.713 and 0.685,
      respectively. Adolescents who were older, had relatively higher level of pubertal
      stages or adolescents from the richer families, tended to underestimate their
      actual level of pubertal maturation while those male subjects and overweight or
      obese subjects were even more likely to be so. CONCLUSION: Using the self
      reported PDS, we could conveniently obtain the necessary information regarding
      sexual maturation among the urban adolescents. It seemed especially useful in the
      related epidemiological survey when physical examination was precluded by cost,
      privacy and other concerns.

PMID- 22883265
TI  - [Prevalence rate regarding the completion of 'recommended physical activities'
      and related influencing factors among junior students in 3 urban districts of
      Hangzhou].
AB  - OBJECTIVE: To explore the rate on completion of the recommended physical
      activities and its correlates among junior students in 3 urban districts of
      Hangzhou. METHODS: Describing the range on completion of the recommended physical
      activities and analyze its related demographic, cognitive and environmental
      factors with logistic regression model among 3867 juniors students. RESULTS: 7.7%
      of the junior students could achieve the recommended physical activities
      requirements. The proportions of students who were aware of the recommendation on
      physical activity programs showed as 31.0%. 59.2% of juniors students had
      physical education (PE) classes in 3 days or more within 1 week. Factors as being
      male (OR = 2.94), believing that adolescents should take part in at least 60
      minutes' physical activities a day (OR = 4.95), having PE classes in 3 days or
      more within 1 week (OR = 1.44), with family encouragement on physical activities
      (OR = 1.06) and taking part in physical activities together (OR = 1.14),
      perceiving the idea that they had enough sports equipment at home (OR = 1.22) and
      had convenient access to sports facilities around the residential areas (OR =
      1.09), and perceiving the idea that it was not safe to walk or jog around the
      residential area (OR = 1.11) etc. had statistically significant correlations with
      achieving the recommended physical activities among juniors students. CONCLUSION:
      Demographic, cognitive and environmental factors had some influence on the
      completion of recommended physical activity program among junior students.

PMID- 22883266
TI  - [Mental disorder and suicide among youths in rural China: a case control study
      based on consecutive samples from Hunan, Liaoning and Shandong provinces].
AB  - OBJECTIVE: To study the prevalence of mental disorders among the Chinese youths
      aged 15 - 34 years, in rural areas and to identify risk factors related to
      suicide. METHODS: A consecutive sampling strategy was used for suicidal cases in
      16 randomly selected counties in Hunan, Liaoning, and Shandong provinces. Between
      2005 and 2008, a total of 392 suicide cases were recruited with 416 community
      controls at the same age range, selected from the same areas one family member
      together with one close friend of each suicidal case were interviewed, using the
      psychological autopsy (PA) method. The same method with structured instruments
      was performed on the two informants for each control in the same community. SCID
      was used for the diagnosis of mental disease. RESULTS: 48.0% of the suicides were
      diagnosed as having at least one mental disorder episode, in comparison with only
      3.8% among the controls. It was found that mental disorder was the most important
      risk factor for the Chinese young suicide cases in the rural areas. CONCLUSION:
      As seen in the Western countries, mental disorder had also been the number one
      correlate on suicidal cases in China, with the difference as other social and
      psychological factors might have played relatively more important roles in China.

PMID- 22883267
TI  - [Study on the single nucleotide polymorphism in capsule plasmid gene of Bacillus
      anthracis in the China isolates].
AB  - OBJECTIVE: To study the characteristic of single nucleotide polymorphism (SNP) in
      capsule plasmid gene of Bacillus anthracis isolated from China. METHODS: 95
      Bacillus anthracis isolates from different sources were selected. 23 SNP sites
      were amplified by PCR method, sequenced and analyzed by clustering analysis.
      RESULTS: 95 Bacillus anthracis isolates were divided into 5 groups by cluster
      analysis. The identified isolates had the same sequence features in 17 sites and
      different nucleotide sequence in the other 6 sites of the 23 SNP sites. 17.89%
      (17/95) of the isolates had homologous locus sequences compared with the
      reference strain Pastuer. 38.95% (37/95) of the isolates had the homologous locus
      sequences compared with the reference strain Ames Ancestor. The remaining strains
      were different from those completed sequenced strains. 3 strains missed length of
      about 80 bp sequence in the PS-34 loci amplified gene fragment in which the
      tested SNP loci were included. 9 strains were amplified negative at all SNP loci
      and Bacillus anthracis capsule plasmid genes were missing which was confirmed by
      capsule plasmid gene-specific primers. CONCLUSION: Results through analysis
      showed that single nucleotide genetic stability and specificity for capsule
      plasmid gene of Bacillus anthracis did exist in the Chinese isolates. The 6
      discriminating SNP sites could be used as indicators in genotyping the Bacillus
      anthracis.

PMID- 22883268
TI  - [Association between peroxisome proliferator-activated receptors gene
      polymorphism and essential hypertension].
AB  - OBJECTIVE: To investigate the association between ten single nucleotide
      polymorphism (SNP) in the peroxisome proliferator-activated receptor (PPAR)
      alpha/delta/gamma and essential hypertension (EH). METHODS: Participants were
      recruited within the framework of a cohort populations survey from the PMMJS
      (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) which was
      conducted in the urban community of Jiangsu province from 1999 to 2007. Eight
      hundred and twenty subjects (551 non-hypertensive subjects, 269 hypertensive
      subjects) were randomly selected but were not related to each other. Ten SNP
      (rs135539, rs1800206, rs4253778 of PPARalpha; rs2016520, rs9794 of PPARdelta;
      rs10865710, rs1805192, rs4684847, rs709158 and rs3856806 of PPARgamma) were
      selected from the HapMap database. chi(2) test was used to determine whether the
      whole population was in H-W genetic equilibrium. SHEsis software was used to
      examine the relations of SNP and linkage equilibrium. Logistic regression model
      was used to examine the association between ten SNP in the PPAR and EH. RESULTS:
      Difference on the distribution of four SNP genotypes including rs1800206, rs9794,
      rs10865710 and rs4684847 between high blood pressure and non-high blood pressure
      group, high systolic blood pressure (SBP) and normal SBP group, high diastolic
      blood pressure (DBP) and normal DBP group was significant (P < 0.05). After
      adjusting factors as age, sex, body mass index, fasting plasma glucose, high
      density lipoprotein cholesterol-C, high-fat diet and compared with wild-type gene
      carriers, the OR (95%CI) of objects with rs1800206 V allele appeared in high
      blood pressure, high SBP and high DBP were 0.60 (0.41 - 0.89), 0.57 (0.37 - 0.88)
      and 0.61 (0.39 - 0.96), respectively. The OR (95%CI) of objects with G allele of
      rs9794 were 0.63 (0.46 - 0.87), 0.51 (0.36 - 0.73) and 0.68 (0.47 - 1.01). The OR
      (95%CI) of objects with G allele of rs10865710 were 1.62 (1.19 - 2.20), 1.59
      (1.14 - 2.22) and 1.53 (1.07 - 2.18), respectively. While the OR (95%CI) of
      objects with rs4684847 T allele were 1.42 (1.04 - 1.94), 1.38 (1.03 - 1.92) and
      1.37 (1.00 - 1.88), respectively. CONCLUSION: The four SNPs including rs1800206
      of PPARalpha, rs9794 of PPARdelta and rs4684847, rs10865710 of PPARgamma
      influenced high blood pressure, high SBP and high DBP to different degrees.

PMID- 22883269
TI  - [Identification and sequential analysis on rabies virus isolated from a donkey].
AB  - OBJECTIVE: To identify and analyze the genetic characteristics of nucleoprotein
      (N) and glycoprotein (G) genes of rabies virus (RABV) isolated from a donkey in
      Wuhan. N gene and G gene of the virus were compared with other representative
      street strains isolated around Hubei areas as well as the vaccine strains used in
      China and abroad. METHODS: RABV in brain tissue of a donkey was detected by
      direct immunofluorescent method and then inoculated in suckling mice to observe
      the incidence of rabies. Brain samples of the donkey and infected suckling mice
      were detected by ELISA. The N gene and G gene fragment of the isolated RABV were
      amplified by RT-PCR and cloned into pMD18-T vector for sequencing and genetic
      analysis. RESULTS: RABVs were detected in both donkey brain and suckling mice
      brain samples. The N gene and G gene nucleotide homology of RABV isolated from
      the donkey with other representative street strains found around Hubei areas as
      well as vaccine strains used in China and abroad were 85.7% - 99.1% and 82.2% -
      99.7%, and the deduced amino acid identity were 95.6% - 99.8% and 87.8% - 99.4%,
      respectively. CONCLUSION: Novel RABV was successfully identified and isolated
      from a donkey and showed close relationship to the representative street strains
      found around Hubei areas as well as vaccine strains used in China through genetic
      analysis.

PMID- 22883270
TI  - [Current status and influencing factors regarding quality of life among patients
      with Alzheimer's disease].
AB  - OBJECTIVE: To investigate the current status and influencing factors regarding
      quality of life among patients with Alzheimer's disease (AD). METHODS: Through
      stratified cluster sampling method, two hundred patients with AD and their
      caregivers were chosen and interviewed. AD patients were assessed by
      questionnaires, Montreal Cognitive Assessment, and Quality of Life-Alzheimer's
      Disease (QOL-AD), in order to compare the reports from patients and caregivers on
      QOL-AD and to analyze related influencing factors. Descriptive analysis, paired t
      test, analysis of variance (ANOVA), Pearson's correlation and multiple linear
      regression were performed using the Statistical Package for Social Science
      (SPSS). RESULTS: The scores of reports from patients (28.78 +/- 4.30) were lower
      than that from the caregivers' (30.05 +/- 6.05). The difference was statistically
      significant (t = 2.122, P < 0.05) and was positively correlated (r = 0.312, P <
      0.001). Data from multivariate analysis showed that cognitive level (t = 3.465, P
      = 0.001), marriage relationship (t = 3.062, P = 0.003), having public activities
      (t = 2.581, P = 0.011), personal characters (t = 2.254, P = 0.026), restricted
      diet pattern (t = 3.614, P < 0.001), regularly drinking tea (t = 2.652, P =
      0.009) and doing housework (t = 3.180, P = 0.002) were predictive factors.
      CONCLUSION: Scores from the caregiver's report on QOL-AD were higher than that
      from the patients'. Many factors influenced the quality of life on AD patients.
      Strategies on improving the quality of life among AD patients can be developed
      based on the findings of this study.

PMID- 22883271
TI  - [Analyses on the relative factors regarding diabetic nephropathy among 1758 cases
      of type 2 diabetic patients].
AB  - OBJECTIVE: To analyze the prevalence rate of diabetic nephropathy (DN) and the
      related factors on DN among type 2 diabetic patients. METHODS: A total number of
      1758 type 2 diabetic patients who were hospitalized in the Beijing Hospital from
      2003 to 2010 were analyzed retrospectively. Three groups were divided according
      to the rate of urinary albumin excretion (UAER). Patients whose UAER < 20 ug/min
      belonged to normal albuminuria (NA) group. The ones whose UAER from 20 to 200
      ug/min belonged to microalbuminuria (MA) group, and the others whose UAER >= 200
      ug/min belonged to large albuminuia (LA) group. The clinical characteristics were
      then compared. The related factors of DN were analyzed. RESULTS: (1) There were
      1246 patients in NA group, 408 patients in MA group, and 104 patients in LA
      group. The constituent ratio of nephropathy was 29.1%. (2) The ages of NA group,
      MA group and LA group were (59.87 +/- 12.77, 62.52 +/- 12.74, 64.44 +/- 12.74)
      years old, respectively, with body mass index (BMI) as (24.90 +/- 3.42, 25.53 +/-
      4.00, 25.53 +/- 3.91) kg/m(2) respectively; duration of diabetes as (8.39 +/-
      7.12, 10.77 +/- 8.02, 12.84 +/- 7.97) years; systolic blood pressure (SBP) as
      (133.42 +/- 18.19, 142.72 +/- 20.21, 151.12 +/- 21.91) mm Hg; diastolic blood
      pressure as (78.75 +/- 10.66, 80.79 +/- 12.21, 83.33 +/- 13.61) mm Hg; fasting
      blood sugar (FBS) as (8.25 +/- 3.43, 9.02 +/- 3.72, 9.22 +/- 4.62) mmol/L;
      glycated hemoglobin (HbA1c) as (8.88 +/- 2.10, 9.34 +/- 2.36, 9.10 +/- 2.36)%;
      uric acid (UA) as (288.04 +/- 90.41, 307.23 +/- 96.96, 374.28 +/- 105.47) mmol/L;
      triglyceride as (1.72 +/- 1.51, 2.06 +/- 1.88, 1.94 +/- 1.42) mmol/L, high
      density lipoprotein cholesterol as (1.08 +/- 0.30, 1.02 +/- 0.29, 1.07 +/- 0.28)
      mmol/L; fasting insulin as (9.24 +/- 9.02, 11.24 +/- 9.74, 11.06 +/- 9.29) uU/ml;
      fasting C peptide as (462.31 +/- 289.94, 510.02 +/- 350.08, 595.93 +/- 445.86)
      pmol/L. There were significant differences between NA, MA and LA groups in all
      above items (P < 0.01 or P < 0.05). (3) Logistic regression analysis showed that
      DN were related with duration of diabetes, BMI, SBP, HbA1c, FBS, UA (OR values
      were 1.041, 1.055, 1.028, 1.116, 1.100, 1.004 respectively, P < 0.05 or P <
      0.01). CONCLUSION: It would be helpful to prevent and retard progression of DN
      that comprehensively controlling high blood glucose, hypertension, hyperuricemia
      and body weight of type 2 diabetic patients.

PMID- 22883272
TI  - [A clinical efficacy and safety study on coronary heart disease and angina
      treatment with Puerarin Injection].
AB  - OBJECTIVE: To observe the clinical efficacy and safety of Puerarin Injection
      treatment on angina pectoris. METHODS: 388 patients with angina pectoris,
      enrolled to Tianjin Fourth Central Hospital during January 2009 and February 2011
      were selected and randomly divided into treatment or control groups with 194
      patients of each. Based on the conventional therapy program, one group was given
      Puerarin Injection as treatment group while, the other was given with Danshen
      Injection as control group. Clinical efficacy, the attack rate of angina
      pectoris, oxygen consumption, indices on electrocardiogram, haemorheology and
      other adverse reactions among the two groups were compared. RESULTS: The total
      efficacy of the treatment group (88.14%, 171/194) was significantly higher than
      the control group (61.86%, 120/194) and the difference was statistically
      significant (P < 0.05). During the treatment, no significant adverse events were
      noticed in both of the two groups of patients. CONCLUSION: The Puerarin Injection
      treatment program on angina pectoris seemed effective and safe.

PMID- 22883273
TI  - [Effect of magnitude and duration on the performance of Cumulative Sum].
AB  - To explore the effect of magnitude and duration on the performance of Cumulative
      Sum (CUSUM), with simulation method used on the subject after the insertion of 11
      outbreak events into baseline data with Poisson distribution. Sensitivity
      fluctuated from 9.1% to 100.0% with specificities higher than 98.6%. Sensitivity
      was significantly correlated with magnitude, and increased along with the
      increase of magnitude. However, no significant correlation was observed between
      sensitivity and duration. A magnitude which was at least 2.6 times higher than
      that of the mean daily baseline could result in the sensitivity of 100.0%. Time
      lag would be improved along with the increase of magnitude. Time between onset
      and detection of an outbreak was no longer than one day when magnitude was more
      than 1.8 of the mean daily baseline. In summary, the performance of CUSUM was
      influenced by magnitude, but not by duration. CUSUM had the advantage of good
      time-lag and high sensitivity when the outbreak magnitude was more than 2.4 time
      over the baseline data.

PMID- 22883274
TI  - [Gene-based principal component logistic regression model and its application on
      genome-wide association study].
AB  - To explore the gene-based principal component logistic regression model and its
      application in genome-wide association study. Using the simulated genome-wide
      single nucleotide polymorphism (SNPs) genotypes data, we proposed a practical
      statistical analysis strategy-'the principal component logistic regression
      model', based on the gene levels to assess the association between genetic
      variations and complex diseases. The simulation results showed that the P value
      of genes in related diseases was the smallest among the results from all the
      genes. The results of simulation indicated that not only it could reduce the
      degree of freedom through hypothesis testing but could also better understand the
      correlations between SNPs. The gene-based principal component logistic regression
      model seemed to have certain statistical power for testing the association
      between genetic genes and diseases in the genome-wide association studies.

PMID- 22883275
TI  - [Eco-geographic landscapes of natural plague foci in China IV. Characterization
      of biovars of Yersinia pestis, China].

PMID- 22883276
TI  - [Application of visualization on emerging infectious disease based on CiteSpace
      II].

PMID- 22883277
TI  - [West Nile virus in the United States from 1999 to 2009].

PMID- 22883278
TI  - Update on the management of Lennox-Gastaut syndrome.
AB  - Lennox-Gastaut syndrome is a severe childhood epilepsy disorder characterized by
      encephalopathy and multiple, often intractable, seizure types. The drop attack is
      the most frequently recognizable seizure type in this patient population, and is
      also the most dangerous physically, thus severely limiting quality of life. The
      diagnosis is confirmed by electroencephalography, for which the classic pattern
      is a slow 2.5 Hz generalized spike-and-wave. Newer pharmacologic treatments
      include rufinimide and clobazam. However, antiepileptic drugs are often exhausted
      in pursuit of seizure control requiring nonpharmacologic interventions. These
      include dietary therapies, vagus nerve stimulation, and epilepsy surgery,
      including corpus callosotomy and focal curative resection. Although large lobar
      resections are often required, very localized, discrete resections may be
      possible, as in symptomatic Lennox-Gastaut syndrome (specifically, hypothalamic
      hamartoma). We review the history of the disease and current management options.

PMID- 22883279
TI  - Patterns of failure in patients with primary intracranial germinoma treated with
      neoadjuvant chemotherapy and radiotherapy.
AB  - External beam radiotherapy has proven effective in managing intracranial
      germinoma. However, concerns regarding long-term neurocognitive and endocrine
      sequelae led to the addition of chemotherapy, to reduce radiation target volumes.
      There is a paucity of data on patterns of failure in patients treated with
      differing radiation field sizes. We review our experience at a tertiary
      children's hospital treating children with intracranial germinoma, using
      induction chemotherapy followed by radiation therapy to various treatment volumes
      (craniospinal irradiation, whole ventricular irradiation, whole brain radiation
      therapy, and focal radiotherapy). Ten patients with primary intracranial
      germinoma, treated from November 1995-March 2011, were included. The primary
      treatment involved platinum-based chemotherapy, followed by definitive
      radiotherapy. The median follow-up period was 4.3 years (range, 0.75-13.25
      years). The 5-year overall survival for the entire group was estimated at 85.7%,
      and the 5-year disease-free survival was estimated at 75.0%. Two treatment
      failures occurred at 5 and 28 months, both in patients with single lesions in the
      pineal region treated with focal radiotherapy only. Based on the patterns of
      failure, our outcomes support the continued use of the whole ventricular field vs
      a focal field, even in patients with limited disease who demonstrate a complete
      response to neoadjuvant chemotherapy.

PMID- 22883280
TI  - Detection of antiphospholipid antibody in children with Henoch-Schonlein purpura
      and central nervous system involvement.
AB  - To explore the mechanisms of central nervous system involvement in children with
      Henoch-Schonlein purpura, levels of lupus anticoagulant, anticardiolipin
      antibodies, and anti-beta2 glycoprotein I antibodies in serum and cerebrospinal
      fluid were determined in 46 cases of Henoch-Schonlein purpura with central
      nervous system involvement. Results indicated that Henoch-Schonlein purpura with
      central nervous system involvement produced a higher total percentage of
      antiphospholipid antibodies in serum and cerebrospinal fluid, compared with viral
      encephalitis control subjects (76.1% vs 10.0% and 71.7% vs 0.0%, respectively; P
      < 0.05). Henoch-Schonlein purpura may be associated with antiphospholipid
      syndrome or antiphospholipid antibodies, which may account for the neurologic
      damage in Henoch-Schonlein purpura.

PMID- 22883281
TI  - Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple
      sclerosis.
AB  - Matrix metalloproteinases and their tissue inhibitors play a key role in the
      pathogenesis of adult-onset multiple sclerosis, and were suggested as biomarkers
      of response to interferon-beta, an established treatment in multiple sclerosis.
      However, data regarding pediatric population are scarce. We determined serum
      levels of matrix metalloproteinase-7, matrix metalloproteinase-9, and tissue
      inhibitor of matrix metalloproteinase-1 in children, and evaluated effects of
      interferon-beta therapy on these measures. Serum samples from 14 children with
      relapsing, remitting multiple sclerosis at baseline and at month 12, and from 15
      controls, were collected. Interferon-beta treatment was initiated in eight
      patients. Mean serum matrix metalloproteinase-9 levels and matrix
      metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio were
      higher in patients compared with controls, and were reduced significantly in
      treated patients at month 12, but did not change in untreated patients. Mean
      matrix metalloproteinase-7 levels were lower in patients compared with controls,
      and increased significantly in the treated group, but did not change
      significantly in the untreated group. In pediatric multiple sclerosis, a shift in
      matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 balance
      toward proteolytic activity is evident, and interferon-beta therapy demonstrates
      a beneficial effect on this disturbed balance.

PMID- 22883282
TI  - Transcranial magnetic stimulation measures in attention-deficit/hyperactivity
      disorder.
AB  - Children affected by attention-deficit/hyperactivity disorder demonstrate
      diminished intrahemispheric inhibition (short interval cortical inhibition), as
      measured by transcranial magnetic stimulation. This study determined whether
      interhemispheric inhibition (ipsilateral silent period latency) correlates with
      clinical behavioral rating and motor control deficits of affected children. In
      114 right-handed children (aged 8-12 years; age/sex-matched; 50 affected, 64
      controls), we performed comprehensive assessments of behavior, motor skills, and
      cognition. Transcranial magnetic stimulation reliably elicited ipsilateral silent
      periods in 54 children (23 affected); all were on average older than those with
      unobtainable measures. Mean ipsilateral silent period latency was 5 milliseconds
      longer in the affected group (P = 0.007). Longer latencies correlated with more
      severe behavioral symptom scores (r = 0.38, P = 0.007), particularly
      hyperactivity (r = 0.39, P = 0.006), and with worse motor ratings on the Physical
      and Neurological Examination for Soft Signs (r = 0.27, P = 0.05). Longer latency
      also correlated with short interval cortical inhibition (r = 0.36, P = 0.008).
      Longer ipsilateral silent period latencies suggest interhemispheric inhibitory
      signaling is slower in affected children. The deficit in this inhibitory measure
      may underlie developmental, behavioral, and motor impairments in children with
      attention-deficit/hyperactivity disorder.

PMID- 22883283
TI  - Evaluation of etiologic and prognostic factors in neonatal convulsions.
AB  - This study evaluated etiologic and risk factors affecting long-term prognoses of
      neurologic outcomes in newborns with neonatal seizures. We enrolled patients at
      chronologic ages of 23-44 months, referred to the Department of Pediatric
      Neurology, Istanbul Medical Faculty, from January 1, 2007-December 31, 2009,
      after manifesting seizures in their first postnatal 28 days. Of 112 newborns, 41
      were female, 71 were male, 33 were preterm, and 79 were full-term. Perinatal
      asphyxia (28.6%) and intracranial hemorrhage (17%) were the most common causes of
      neonatal seizures. Cerebral palsy developed in 27.6% of patients during follow
      up. The incidence of epilepsy was 35.7%. Almost 50% of patients manifested
      developmental delay in one or more areas. Global developmental delay was the most
      common (50.8%) neurologic disorder. The correlation between gestational age or
      birth weight and adverse outcomes was nonsignificant. Etiology, Apgar score, need
      for resuscitation at birth, background electroencephalogram, neonatal status
      epilepticus, cranial imaging findings, type/duration of antiepileptic treatment,
      and response to acute treatment were all strong prognostic factors in neurologic
      outcomes. Neonatal seizures pose a threat of neurologic sequelae for preterm and
      full-term infants. Although the number of recognized etiologic factors in
      neonatal seizures has increased because of improvements in neonatology and
      diagnostic methods, perinatal asphyxia remains the most common factor.

PMID- 22883284
TI  - Decompressive craniectomy in childhood posterior circulation stroke: a case
      series and review of the literature.
AB  - Few reports address the role of decompressive craniectomy in children with space
      occupying cerebral edema attributable to severe ischemic infarction of the
      posterior cerebral arterial circulation. We describe four children with posterior
      circulation arterial ischemic stroke who required decompressive craniectomy.
      These children accounted for 11% of all cases of posterior circulation ischemic
      stroke at our institution from 2002-2010. Three manifested large, cerebellar
      hemispheric infarcts, and one manifested a large, temporo-occipital posterior
      cerebral artery infarct. Deterioration occurred within 72 hours of stroke onset.
      Two patients demonstrated minimal functional deficits at follow-up, and two
      demonstrated moderate deficits with functional limitations. Because decompressive
      craniectomy can be lifesaving in children with severe posterior circulation
      arterial ischemic stroke, early neurosurgical referral should be considered.

PMID- 22883285
TI  - Idiopathic cranial polyneuropathy with unilateral IX and X and contralateral XI
      nerve palsy in a 4-year-old boy.
AB  - A 4-year-old boy presented with a sudden onset of nasal escape of fluids, nasal
      speech, and difficulty placing his left arm through a sleeve. Neurologic
      examination indicated a unilateral cranial IX and X and contralateral XI nerve
      palsy that was considered idiopathic. Palsy of cranial nerves IX, X, and XI is
      rare in childhood, and few reports have described this condition. Our patient
      received prednisolone for 1 week and demonstrated complete recovery within
      several weeks. We suggest that aggressive therapy is unnecessary for patients
      with idiopathic cranial polyneuropathy. The pathogenesis of this condition may
      involve an immunologic mechanism.

PMID- 22883286
TI  - Variable manifestations of familial hemiplegic migraine associated with
      reversible cerebral edema in children.
AB  - Three children with familial hemiplegic migraine presented with right-sided
      weakness, speech difficulty, altered mental status, and gait abnormalities. These
      persistent aura signs were accompanied by left-sided slowing and cerebral
      dysfunction, documented by electroencephalograms. Cranial magnetic resonance
      imaging revealed cortical edema restricted to the left cerebral hemisphere.
      Follow-up electroencephalogram and imaging studies produced normal results 1-4
      months afterward. However, cognitive changes persisted. Genetic testing
      demonstrated variable results: one child manifested a CACNA1A mutation compatible
      with familial hemiplegic migraine type 1, whereas another demonstrated an ATP1A2
      sequence alteration. No known mutations were evident in the third child, with
      minor head trauma thought to precipitate the familial hemiplegic migraine. These
      findings demonstrate the variable clinical and genetic heterogeneity of childhood
      familial hemiplegic migraine.

PMID- 22883287
TI  - Mutation of the CLN6 gene in teenage-onset progressive myoclonus epilepsy.
AB  - Progressive myoclonus epilepsies are severe, intractable, and neurodegenerative.
      They afflict patients of all ages, but more commonly adolescents, and comprise
      the main differential diagnosis of common juvenile myoclonic epilepsy. Genetic or
      minimally invasive pathologic diagnoses are available for many but not all
      teenage-onset progressive myoclonus epilepsies. We describe a multiplex family
      with autosomal recessive teenage-onset progressive myoclonus epilepsy that had
      remained undiagnosed despite extensive genetic and pathologic testing. We
      describe whole exome sequencing combined with homozygosity mapping to identify
      the disease gene directly and diagnose the family. The affected gene is CLN6,
      previously known to underlie variant late-infantile and adult-onset neuronal
      ceroid lipofuscinoses. Combined with other recent work, our results add CLN6 to
      the genetic mutations causing teenage-onset progressive myoclonus epilepsy,
      expand the group of teenage-onset progressive myoclonus epilepsy patients who can
      be diagnosed by genetic testing, and extend the clinical spectrum of CLN6
      mutations to include teenage-onset progressive myoclonus epilepsy. This work also
      exemplifies the potentiality of next-generation sequencing in the genetic
      identification and diagnosis of patients with neurologic diseases of unknown
      cause.

PMID- 22883288
TI  - Rituximab in severe seronegative juvenile myasthenia gravis: review of the
      literature.
AB  - Myasthenia gravis is an autoimmune neuromuscular disorder caused by circulating
      antibodies that block acetylcholine receptors at the postsynaptic neuromuscular
      junction. A wide range of symptomatic therapy with acetylcholinesterase
      inhibitors and immunotherapy such as corticosteroids, azathioprine, cyclosporine,
      mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin has been
      used in the treatment of myasthenia gravis, with variable responses. However,
      most modalities of treatment involve delayed onset of action. We describe a child
      with severe, life-threatening seronegative myasthenia gravis who repeatedly
      failed extubation and responded dramatically to rituximab. She achieved complete
      and sustained remission for more than 9 months, with gradual reduction in steroid
      dose without any side effects. Advances in the treatment of myasthenia gravis
      have reduced mortality and morbidity and improved the quality of life in these
      patients.

PMID- 22883289
TI  - Anti-GQ1b-negative Miller Fisher syndrome after Campylobacter jejuni enteritis.
AB  - Miller Fisher syndrome is a clinical variant of Guillain-Barre syndrome,
      characterized by acute-onset ophthalmoplegia, ataxia, and areflexia. It results
      from an immune response to a cross-reactive antigen between GQ1b ganglioside in
      human neurons and lipo-oligosaccharides of certain bacteria, e.g., Campylobacter
      jejuni. Anti-GQ1b antibody is a powerful diagnostic marker for Miller Fisher
      syndrome. However, only a small number of anti-GQ1b-negative Miller Fisher
      syndrome cases are documented. A 13-year-old boy demonstrated typical clinical
      features of Miller Fisher syndrome 1 week after C. jejuni enteritis, but was anti
      GQ1b and anti-GM1b antibody-negative.

PMID- 22883290
TI  - Acute, sustained chorea in children after supratherapeutic dosing of amphetamine
      derived medications.
AB  - Amphetamine-derived medications are being prescribed with increasing frequency to
      younger pediatric patients to treat attention deficit hyperactivity disorder.
      Although choreiform movements were reported in adults with amphetamine abuse and
      in those under therapeutic treatment for attention deficit hyperactivity
      disorder, previous literature concerning the pediatric population is spare. We
      describe two children who developed chorea after ingesting amphetamine-derived
      medications prescribed to treat attention deficit hyperactivity disorder. Patient
      1, a 10-year-old boy, accidently received an extra dose of lisdexamfetamine
      dimesylate the night before the onset of acute chorea involving his arms, legs,
      and trunk. Patient 2, an 8-month-old boy, accidentally ingested his stepbrother's
      mixed amphetamine salts (Adderall XR) and developed acute chorea.
      Benzodiazepines, diphenhydramine, benztropine, and opioids did not suppress the
      chorea in either case. The 10-year-old received haloperidol, which significantly
      improved his abnormal findings, and he returned to baseline in approximately 48
      hours. The 8-month-old was observed in the pediatric intensive care unit, and his
      signs resolved by 72 hours. Our cases demonstrate that choreiform movements of
      sustained duration can occur in children with acute supratherapeutic ingestions
      of amphetamine-derived medications.

PMID- 22883291
TI  - Stability of intellectual functioning during maintenance electroconvulsive
      therapy.
AB  - We describe the stability of neuropsychologic testing in a 16-year-old boy with
      cerebellar dysgenesis who received 61 acute and maintenance electroconvulsive
      therapy treatments for malignant catatonia. Measures of nonverbal intelligence
      and visual memory before treatment onset and after 61 electroconvulsive therapy
      treatments indicated no evidence of decline in intellectual functioning and acute
      or delayed memory. This case offers further support for the safety and efficacy
      of maintenance electroconvulsive therapy in both pediatric and developmentally
      disabled populations.

PMID- 22883292
TI  - Focal meningoencephalitis of hepatitis A: a clinico-radiologic picture.

PMID- 22883293
TI  - Bhuwan Garg, MBBS, 1944-2012.

PMID- 22883295
TI  - Shapiro-Shulman and Sturge-Weber syndromes.

PMID- 22883297
TI  - Isolated neonatal seizures: adenylosuccinase deficiency is another cause!

PMID- 22883298
TI  - Epilepsy of infancy with migrating focal seizures: a structural abnormality or a
      metabolic disturbance?

PMID- 22883301
TI  - Clinical features of bleb-related infection: a 5-year survey in Japan.
AB  - PURPOSE: To present clinical features and microbial data for bleb-related
      infections obtained by the 5-year-long Japan Glaucoma Society Survey of Bleb
      related Infection (JGSSBI). METHODS: This multicentre prospective observational
      study was conducted in 82 clinical centres in Japan. A total of 170 bleb-related
      infections developed in 157 eyes of 156 patients during a 5-year period. The
      ophthalmological and microbial data were analysed. RESULTS: The patient age at
      first infection was 59.3 +/- 17.7 years [mean +/- standard deviation (SD)], and
      the period between the last glaucoma surgery and the first infection was 6.9 +/-
      5.8 years (mean +/- SD; range: 0.3-41 years). Bleb leakage was noted
      significantly more frequently in eyes with repeated infections. The stage of
      infection at diagnosis was stage I in 91 infections (54%), stage II in 30
      infections (18%), stage IIIa in 18 infections (11%), and stage IIIb in 31
      infections (18%). Staphylococcus species were the most frequently isolated
      microbe (41%), followed by Streptococcus species (32%). Streptococcus species,
      coagulase-negative Staphylococcus, Haemophilus influenzae, and Enterococcus
      species were the major bacteria isolated in the late-stage infections.
      CONCLUSIONS: The JGSSBI project has revealed several characteristics of bleb
      related infection in Japan, which include the significance of bleb leakage in the
      development of repeated infections and the distribution of bacterial isolates.

PMID- 22883300
TI  - Goat milk with and without increased concentrations of lysozyme improves repair
      of intestinal cell damage induced by enteroaggregative Escherichia coli.
AB  - BACKGROUND: Enteroaggregative Escherichia coli (EAEC) causes diarrhea,
      malnutrition and poor growth in children. Human breast milk decreases disease
      causing bacteria by supplying nutrients and antimicrobial factors such as
      lysozyme. Goat milk with and without human lysozyme (HLZ) may improve the repair
      of intestinal barrier function damage induced by EAEC. This work investigates the
      effect of the milks on intestinal barrier function repair, bacterial adherence in
      Caco-2 and HEp-2 cells, intestinal cell proliferation, migration, viability and
      apoptosis in IEC-6 cells in the absence or presence of EAEC. METHODS: Rat
      intestinal epithelial cells (IEC-6, ATCC, Rockville, MD) were used for
      proliferation, migration and viability assays and human colon adenocarcinoma
      (Caco-2, ATCC, Rockville, MD) and human larynx carcinoma (HEp-2, ATCC, Rockville,
      MD) cells were used for bacterial adhesion assays. Goats expressing HLZ in their
      milk were generated and express HLZ in milk at concentration of 270 MUg/ml. Cells
      were incubated with pasteurized milk from either transgenic goats expressing HLZ
      or non-transgenic control goats in the presence and absence of EAEC strain 042
      (O44:H18). RESULTS: Cellular proliferation was significantly greater in the
      presence of both HLZ transgenic and control goat milk compared to cells with no
      milk. Cellular migration was significantly decreased in the presence of EAEC
      alone but was restored in the presence of milk. Milk from HLZ transgenic goats
      had significantly more migration compared to control milk. Both milks
      significantly reduced EAEC adhesion to Caco-2 cells and transgenic milk resulted
      in less colonization than control milk using a HEp-2 assay. Both milks had
      significantly increased cellular viability as well as less apoptosis in both the
      absence and presence of EAEC. CONCLUSIONS: These data demonstrated that goat milk
      is able to repair intestinal barrier function damage induced by EAEC and that
      goat milk with a higher concentration of lysozyme offers additional protection.

PMID- 22883302
TI  - Acute responses of DNA repair proteins and StarD6 in rat hippocampus after domoic
      acid-induced excitotoxicity.
AB  - StarD6, which might be considered to be neuroprotective, and DNA repair proteins
      can play a role against oxidative damages by excitotoxin in the nervous system.
      In order to investigate the relationship between StarD6 and DNA repair proteins,
      excitotoxicity was induced by domoic acid in male Sprague-Dawley rats. Western
      blot analysis revealed transitorily elevated levels in StarD6,
      apurinic/apyrimidinic endonuclease (APE) and 8-oxoguanine DNA-glycosylase (Ogg1)
      in accord with the DNA damage marker phosphorylated H2AX. Immunohistochemistry
      revealed that increased intensity was transiently seen not only in the Stratum
      (Str.) radiatum and Str. lacunosum-moleculare with StarD6 and APE, but also in
      the Str. pyramidale with Ogg1. Intensities decreased 24h after domoic acid
      injection in CA3 with APE and Ogg1 as well as in the Str. radiatum and Str.
      lacunosum-moleculare with StarD6 and APE. These results suggested that StarD6 may
      not be closely related with DNA repair proteins in the hippocampus after domoic
      acid-induced excitotoxicity, although the activities of these proteins might be
      positively affected by excitotoxic stimuli.

PMID- 22883303
TI  - Learning invariant face recognition from examples.
AB  - Autonomous learning is demonstrated by living beings that learn visual
      invariances during their visual experience. Standard neural network models do not
      show this sort of learning. On the example of face recognition in different
      situations we propose a learning process that separates learning of the
      invariance proper from learning new instances of individuals. The invariance is
      learned by a set of examples called model, which contains instances of all
      situations. New instances are compared with these on the basis of rank lists,
      which allow generalization across situations. The result is also implemented as a
      spike-time-based neural network, which is shown to be robust against
      disturbances. The learning capability is demonstrated by recognition experiments
      on a set of standard face databases.

PMID- 22883304
TI  - Bioactive derivatives of curcumin attenuate cataract formation in vitro.
AB  - In this study, curcumin derivatives salicylidenecurcumin (CD1) and
      benzalidenecurcumin (CD2)] were prepared, and their biological activity was
      compared in in vitro selenite-induced cataract model. The antioxidant activity
      was studied using DPPH radical scavenging assay. Knoevenagel condensates of
      curcumin exhibited higher DPPH radical scavenging activity compared with
      curcumin. The anticataractogenic potential of curcumin derivatives was analyzed
      using lens organ culture method. The activity of antioxidant enzymes and calcium
      homeostasis was reversed to near normal levels following treatment in organ
      cultured rat lenses. These results indicated that curcumin and its derivatives-
      CD1 and CD2--are beneficial against selenite-induced cataract in vitro. Of these,
      CD1 is having higher bioactive potential compared with curcumin and CD2.

PMID- 22883305
TI  - Idiopathic environmental intolerance attributed to electromagnetic fields (IEI
      EMF): a systematic review of identifying criteria.
AB  - BACKGROUND: Idiopathic environmental intolerance attributed to electromagnetic
      fields (IEI-EMF) remains a complex and unclear phenomenon, often characterized by
      the report of various, non-specific physical symptoms (NSPS) when an EMF source
      is present or perceived by the individual. The lack of validated criteria for
      defining and assessing IEI-EMF affects the quality of the relevant research,
      hindering not only the comparison or integration of study findings, but also the
      identification and management of patients by health care providers. The objective
      of this review was to evaluate and summarize the criteria that previous studies
      employed to identify IEI-EMF participants. METHODS: An extensive literature
      search was performed for studies published up to June 2011. We searched EMBASE,
      Medline, Psychinfo, Scopus and Web of Science. Additionally, citation analyses
      were performed for key papers, reference sections of relevant papers were
      searched, conference proceedings were examined and a literature database held by
      the Mobile Phones Research Unit of King's College London was reviewed. RESULTS:
      Sixty-three studies were included. "Hypersensitivity to EMF" was the most
      frequently used descriptive term. Despite heterogeneity, the criteria
      predominantly used to identify IEI-EMF individuals were: 1. Self-report of being
      (hyper)sensitive to EMF. 2. Attribution of NSPS to at least one EMF source. 3.
      Absence of medical or psychiatric/psychological disorder capable of accounting
      for these symptoms 4. Symptoms should occur soon (up to 24 hours) after the
      individual perceives an exposure source or exposed area. (Hyper)sensitivity to
      EMF was either generalized (attribution to various EMF sources) or source
      specific. Experimental studies used a larger number of criteria than those of
      observational design and performed more frequently a medical examination or
      interview as prerequisite for inclusion. CONCLUSIONS: Considerable heterogeneity
      exists in the criteria used by the researchers to identify IEI-EMF, due to
      explicit differences in their conceptual frameworks. Further work is required to
      produce consensus criteria not only for research purposes but also for use in
      clinical practice. This could be achieved by the development of an international
      protocol enabling a clearly defined case definition for IEI-EMF and a validated
      screening tool, with active involvement of medical practitioners.

PMID- 22883306
TI  - Immunology of BVDV vaccines.
AB  - Providing acquired immune protection against infection with bovine viral diarrhea
      viruses (BVDV) is challenging due to the heterogeneity that exists among BVDV
      strains and the ability of the virus to infect the fetus and establish persistent
      infections. Both modified live and killed vaccines have been shown to be
      efficacious under controlled conditions. Both humoral and cellular immune
      responses are protective. Following natural infection or vaccination with a
      modified live vaccine, the majority of the B cell response (as measured by serum
      antibodies) is directed against the viral proteins E2 and NS2/3, with minor
      responses against the Erns and E1 proteins. Vaccination with killed vaccines
      results in serum antibodies directed mainly at the E2 protein. It appears that
      the major neutralizing epitopes are conformational and are located within the N
      terminal half of the E2 protein. While it is thought that the E2 and NS2/3
      proteins induce protective T cell responses, these epitopes have not been mapped.
      Prevention of fetal infections requires T and B cell response levels that
      approach sterilizing immunity. The heterogeneity that exists among circulating
      BVDV strains, works against establishing such immunity. Vaccination, while not
      100% effective in every individual animal, is effective at the herd level.

PMID- 22883307
TI  - Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest
      compression device, prehospital intraarrest cooling, extracorporeal life support
      and early invasive assessment compared to standard of care. A randomized parallel
      groups comparative study proposal. "Prague OHCA study".
AB  - BACKGROUND: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non
      randomized studies of ECLS (extracorporeal life support) in OHCA suggested
      further prospective multicenter studies to define population that would benefit
      from ECLS. We aim to perform a prospective randomized study comparing prehospital
      intraarrest hypothermia combined with mechanical chest compression device,
      intrahospital ECLS and early invasive investigation and treatment in all patients
      with OHCA of presumed cardiac origin compared to a standard of care. METHODS:
      This paper describes methodology and design of the proposed trial. Patients with
      witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum
      of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service
      (EMS) team and after performance of all initial procedures (defibrillation,
      airway management, intravenous access establishment) will be randomized to
      standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression
      device together with intranasal evaporative cooling will be instituted and
      patients will be transferred directly to cardiac center under ongoing CPR
      (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion
      criteria will be evaluated and if achieved, veno-arterial ECLS will be started.
      Invasive investigation and standard post resuscitation care will follow. Patients
      in standard arm will be managed on scene. When ROSC achieved, they will be
      transferred to cardiac center and further treated as per recent guidelines.
      PRIMARY OUTCOME: 6 months survival with good neurological outcome (Cerebral
      Performance Category 1-2). Secondary outcomes will include 30 day neurological
      and cardiac recovery. DISCUSSION: Authors introduce and offer a protocol of a
      proposed randomized study comparing a combined "hyperinvasive approach" to a
      standard of care in refractory OHCA. The protocol is opened for sharing by other
      cardiac centers with available ECLS and cathlab teams trained to admit patients
      with refractory cardiac arrest under ongoing CPR. A prove of concept study will
      be started soon. The aim of the authors is to establish a net of centers for a
      multicenter trial initiation in future. ETHICS AND REGISTRATION: The protocol has
      been approved by an Institutional Review Board, will be supported by a research
      grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT
      13225-4/2012 and has been registered under ClinicalTrials.gov identifier:
      NCT01511666.

PMID- 22883308
TI  - Taok2 controls behavioral response to ethanol in mice.
AB  - Despite recent advances in the understanding of ethanol's biological action, many
      of the molecular targets of ethanol and mechanisms behind ethanol's effect on
      behavior remain poorly understood. In an effort to identify novel genes, the
      products of which regulate behavioral responses to ethanol, we recently
      identified a mutation in the dtao gene that confers resistance to the locomotor
      stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20
      family of serine/threonine kinases implicated in MAP kinase signaling pathways.
      In this study, we report that conditional ablation of the mouse dtao homolog,
      Taok2, constitutively and specifically in the nervous system, results in strain
      specific and overlapping alterations in ethanol-dependent behaviors. These data
      suggest a functional conservation of dtao and Taok2 in mediating ethanol's
      biological action and identify Taok2 as a putative candidate gene for ethanol use
      disorders in humans.

PMID- 22883309
TI  - Hospitalizations from pandemic Influenza [A(H1N1)pdm09] infections among type 1
      and 2 diabetes patients in Spain.
AB  - OBJECTIVES: To describe and analyze the clinical characteristics and outcomes for
      all patients with diabetes who were hospitalized with laboratory-confirmed
      A(H1N1)pdm09 infections in Spain during 2009. METHODS: Observational
      retrospective study using data collected by the Spanish National Hospital
      Discharge Database. We selected all admissions with diagnosis ICD-9-CM code 488.1
      [A(H1N1)pdm09]. Discharges were grouped as follows: no diabetes, Type1 and Type 2
      diabetes. Underlying medical conditions and risk factors included all those that
      constitute an indication for annual influenza vaccination, pregnancy, and
      obesity. The outcome variables analyzed were in-hospital case fatality risk,
      length of hospital stay, and costs. RESULTS: The total number of persons
      hospitalized with A(H1N1)pdm09 was 11,499. Of those, 97 suffered Type 1 and 936
      Type 2, giving an overall prevalence of diabetes of 9%. The most common
      underlying medical condition among Type 2 subjects was obesity (26.8%), and for
      Type 1 renal disease (10.3%). In-hospital mortality was 2.1% among Type 1
      patients, 3.8% among Type 2 patients, and 2.3% among non-diabetics; after
      multivariate analysis, diabetes was not a factor independently associated with
      dying during hospitalization for A(H1N1)pdm09. Independent factors increasing the
      risk of death among diabetic patients included age (OR 1.03; 95% CI1.01-1.05),
      hematological disorders (OR 3.49; 95% CI, 1.46-8.37), and obesity (OR 1.88; 95%
      CI1.07-3.92). CONCLUSIONS: Among individuals hospitalized in Spain with
      A(H1N1)pdm09 infections, the age-specific prevalence of diabetes was higher than
      the general population in most age groups. The results of multivariate analysis
      suggest that possibly concomitant conditions such as obesity increase the risk of
      dying from the infection, but not diabetes itself.

PMID- 22883310
TI  - Sunshine virus in Australian pythons.
AB  - Sunshine virus is a recently discovered novel paramyxovirus that is associated
      with illness in snakes. It does not phylogenetically cluster within either of the
      two currently accepted paramyxoviral subfamilies. It is therefore only distantly
      related to the only other known genus of reptilian paramyxoviruses, Ferlavirus,
      which clusters within the Paramyxovirinae subfamily. Clinical and diagnostic
      aspects associated with Sunshine virus are as yet undescribed. The objective of
      this paper was to report the clinical presentation, virus isolation, PCR testing
      and pathology associated with Sunshine virus infection. Clinical records and
      samples from naturally occurring cases were obtained from two captive snake
      collections and the archives of a veterinary diagnostic laboratory. The clinical
      signs that are associated with Sunshine virus infection are localised to the
      neurorespiratory systems or are non-specific (e.g. lethargy, inappetence). Out of
      15 snakes that were infected with Sunshine virus (detected in any organ by either
      virus isolation or PCR), the virus was isolated from four out of ten (4/10)
      sampled brains, 3/10 sampled lungs and 2/7 pooled samples of kidney and liver. In
      these same 15 snakes, PCR was able to successfully detect Sunshine virus in fresh
      frozen brain (11/11), kidney (7/8), lung (8/11) and liver (5/8); and various
      formalin-fixed paraffin-embedded tissues (7/8). During a natural outbreak of
      Sunshine virus in a collection of 32 snakes, the virus could be detected in five
      out of 39 combined oral-cloacal swabs that were collected from 23 of these snakes
      over a 105 day period. All snakes that were infected with Sunshine virus were
      negative for reovirus and ferlavirus by PCR. Snakes infected with Sunshine virus
      reliably exhibited hindbrain white matter spongiosis and gliosis with extension
      to the surrounding grey matter and neuronal necrosis evident in severe cases.
      Five out of eight infected snakes also exhibited mild bronchointerstitial
      pneumonia. Infection with Sunshine virus should be considered by veterinarians
      investigating disease outbreaks in snakes, particularly those that are associated
      with neurorespiratory disease.

PMID- 22883311
TI  - Medical students benefit from the use of ultrasound when learning peripheral IV
      techniques.
AB  - BACKGROUND: Recent studies support high success rates after a short learning
      period of ultrasound IV technique, and increased patient and provider
      satisfaction when using ultrasound as an adjunct to peripheral IV placement. No
      study to date has addressed the efficacy for instructing ultrasound-naive
      providers. We studied the introduction of ultrasound to the teaching technique of
      peripheral IV insertion on first- and second-year medical students. METHODS: This
      was a prospective, randomized, and controlled trial. A total of 69 medical
      students were randomly assigned to the control group with a classic, landmark
      based approach (n = 36) or the real-time ultrasound-guided group (n = 33). Both
      groups observed a 20-min tutorial on IV placement using both techniques and then
      attempted vein cannulation. Students were given a survey to report their results
      and observations by a 10-cm visual analog scale. The survey response rate was
      100%. RESULTS: In the two groups, 73.9% stated that they attempted an IV
      previously, and 63.7% of students had used an ultrasound machine prior to the
      study. None had used ultrasound for IV access prior to our session. The average
      number of attempts at cannulation was 1.42 in either group. There was no
      difference between the control and ultrasound groups in terms of number of
      attempts (p = 0.31). In both groups, 66.7% of learners were able to cannulate in
      one attempt, 21.7% in two attempts, and 11.6% in three attempts. The study group
      commented that they felt they gained more knowledge from the experience (p <
      0.005) and that it was easier with ultrasound guidance (p < 0.005). CONCLUSION:
      Medical students feel they learn more when using ultrasound after a 20-min
      tutorial to place IVs and cannulation of the vein feels easier. Success rates are
      comparable between the traditional and ultrasound teaching approaches.

PMID- 22883312
TI  - Advanced therapeutic strategy for radiation-induced osteosarcoma in the skull
      base: a case report and review.
AB  - A review of patients with skull base osteosarcoma secondary to radiation
      (radiation-induced osteosarcoma: RIOS) of the pituitary tumor shows the mean
      survival of approximately 7 months (2 weeks-16 months). This warning prognosis
      seems to stem from two factors, 1) the anatomical complexity of the skull base
      for total resection of the tumor, and 2) standard adjuvant therapies for the
      tumor yet to be established. Contrary to the general belief, the authors report
      an unusually long survival of a 75-year-old woman with a history of osteosarcoma
      that developed in the same sequence 20 years after pituitary tumor radiation. On
      her recent admission, she complained of frontal headaches and MRI studies showed
      a tumor in the sphenoid sinus. Endoscopic trans-nasal tumor removal allowed for
      histological diagnosis of an osteosarcoma. However, further rapid tumor growth
      necessitated a radical tumor resection followed by a combined chemotherapy with
      ifosfamide, cisplatin, and etoposide (ICE). Despite temporary suppression of the
      tumor growth, the chemotherapy was discontinued due to severe pancytopenia that
      occurred after three courses of treatment. Shortly after the discontinuation of
      ICE therapy, the tumor size increased again rapidly, requiring a novel radiation
      therapy, Cyber-knife treatment. Following this radiation, the tumor growth was
      arrested, and the patient remains healthy without neurological symptoms over 24
      months. The outcome of Cyber-knife in this case suggests that this specific
      therapy must be considered for the unresectable skull base RIOS.

PMID- 22883313
TI  - Reducing pediatric liver transplant complications: a potential roadmap for
      transplant quality improvement initiatives within North America.
AB  - Though robust clinical data are available within transplantation, these data are
      not used for broad-based, multicentered quality improvement initiates. This
      article describes a targeted quality improvement initiative within the Studies of
      Pediatric Liver Transplantation (SPLIT) Registry. Using standard statistical
      techniques and clinical expertise to adjust for data and statistical reliability,
      we identified the pediatric liver transplant centers in North America with the
      lowest hepatic artery thrombosis rate and biliary complication rates. A survey
      was completed to establish current practices within the entire SPLIT group.
      Surgeons from the highest performing centers presented a detailed, technically
      oriented overview of their current practices. The presentations and discussion
      that followed were recorded and form the basis of the best practices described
      herein. We frame this work as a unique six-step approach roadmap that may serve
      as an efficient and cost effective model for novel broad-based quality
      improvement initiatives within transplantation.

PMID- 22883315
TI  - High-dose desvenlafaxine in outpatients with major depressive disorder.
AB  - OBJECTIVE: This study investigated the safety and efficacy of long-term treatment
      with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major
      depressive disorder (MDD). METHODS: In this multicenter, open-label study, adult
      outpatients with MDD aged 18-75 were treated with flexible doses of
      desvenlafaxine (200-400 mg/d) for <= 1 year. Safety assessments included
      monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations
      due to adverse events, electrocardiograms, vital signs, and laboratory
      determinations. The primary efficacy measure was mean change from baseline in the
      17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. RESULTS:
      The mean daily desvenlafaxine dose range over the duration of the trial was 267
      356 mg (after titration). The most frequent TEAEs in the safety population (n =
      104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and
      dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%)
      patients discontinued from the study because of TEAEs; nausea (12%) and dizziness
      (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total
      score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy
      visit in the last-observation-carried-forward analysis and -14.0 at month 12 in
      the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d)
      was generally safe and effective in the long-term treatment of MDD.

PMID- 22883314
TI  - Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide
      in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and
      inflammation in mice.
AB  - Dietary intake of linoleic acid (LA) has increased dramatically during the
      twentieth century and is associated with a greater prevalence of obesity.
      Vegetable oils are recognised as suitable alternatives to fish oil (FO) in feed
      for Atlantic salmon (Salmo salar L.) but introduce high amounts of LA in the
      salmon fillet. The effect on fish consumers of such a replacement remains to be
      elucidated. Here, we investigate the effect of excessive dietary LA from soyabean
      oil (SO) on endocannabinoid levels in Atlantic salmon and mice, and study the
      metabolic effects in mice when SO replaces FO in feed for Atlantic salmon.
      Atlantic salmon were fed FO and SO for 6 months, and the salmon fillet was used
      to produce feed for mice. Male C57BL/6J mice were fed diets of 35% of energy as
      fat based on FO- and SO-enriched salmon for 16 weeks. We found that replacing FO
      with SO in feed for Atlantic salmon increased LA, arachidonic acid (AA),
      decreased EPA and DHA, elevated the endocannabinoids 2-arachidonoylglycerol (2
      AG) and anandamide (AEA), and increased TAG accumulation in the salmon liver. In
      mice, the SO salmon diet increased LA and AA and decreased EPA and DHA in the
      liver and erythrocyte phospholipids, and elevated 2-AG and AEA associated with
      increased feed efficiency, weight gain and adipose tissue inflammation compared
      with mice fed the FO salmon diet. In conclusion, excessive dietary LA elevates
      endocannabinoids in the liver of salmon and mice, and increases weight gain and
      counteracts the anti-inflammatory properties of EPA and DHA in mice.

PMID- 22883316
TI  - Reduced left ventricular compacta thickness: a novel echocardiographic criterion
      for non-compaction cardiomyopathy.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) is characterized by a two
      layered myocardium consisting of a noncompacted inner and a compacted outer
      layer. The ratio of the thicknesses of these two layers is a major diagnostic
      criterion, which is, however, often difficult to apply in clinical practice.
      METHODS: Transthoracic echocardiography was performed in 41 patients with LVNC,
      41 patients with moderate or severe aortic valve stenosis (AVS), and 41 age
      matched normal controls. The maximal systolic thicknesses of "noncompacta" and
      "compacta" were measured in standard short-axis views at the apical or
      midventricular level, in the segment with most prominent recesses (in patients
      with LVNC) or trabeculation (in patients with AVS and controls). RESULTS: The
      mean maximal systolic thickness of noncompacta was 1.8 +/- 0.4 cm in patients
      with LVNC compared with 0.2 +/- 0.1 cm in controls and 0.6 +/- 0.02 cm in
      patients with AVS (P < .0001). The mean maximal systolic thickness of compacta
      was lower in patients with LVNC (0.5 +/- 0.1 cm) compared to controls (1.2 +/-
      0.2 cm; P < .0001) and patients with AVS (1.6 +/- 0.06 cm; P < .0001). The
      maximal systolic thickness of compacta was <=8.1 mm in patients with LVNC
      compared with >8.1 mm (P < .0001) in controls and >8.1 mm in patients with AVS (P
      < .0001). The ratio of the maximal systolic thickness of the indexed basal septum
      to that of the compacta was >=0.64/m(2) in patients with LVNC compared to
      <=0.62/m(2) in controls and <=0.96/m(2) in patients with AVS. CONCLUSIONS:
      Maximal systolic compacta thickness <8 mm is specific for LVNC and allows the
      differentiation of LVNC from normal hearts as well as those with myocardial
      thickening due to AVS. This observation may be particularly useful as an
      additional diagnostic criterion for preventing the overdiagnosis of LVNC.

PMID- 22883317
TI  - Monkeys exhibit prospective memory in a computerized task.
AB  - Prospective memory (PM) involves forming intentions, retaining those intentions,
      and later executing those intended responses at the appropriate time. Few studies
      have investigated this capacity in animals. Monkeys performed a computerized task
      that assessed their ability to remember to make a particular response if they
      observed a PM cue embedded within an ongoing learning-set (LS) task. At a break
      in the LS task, monkeys selected one of two icons indicating that they had or had
      not encoded the occurrence of the PM cue (the latter icon resumed the LS task).
      Critically, during this response period, the PM response icon appeared after a
      delay during which monkeys could self-initiate the PM response prior to receiving
      any external prompt. Monkeys selected the PM and LS icons when each was the
      optimal response, illustrating that they could encode, store, and respond
      appropriately to a stimulus event in the future. Critically, some monkeys self
      initiated the PM response prior to that icon's appearance, indicating that they
      could retrieve the PM and act on their intention to make that response without
      the aid of a prompt. These monkeys appeared capable of using PM in this task.
      Thus, this capacity appears not to be limited to humans.

PMID- 22883318
TI  - Nasal airway function after maxillary surgery: a prospective cohort study using
      the nasal obstruction symptom evaluation scale.
AB  - PURPOSE: To examine nasal airway function using a disease-specific quality-of
      life survey instrument in subjects undergoing Le Fort I osteotomy without
      simultaneous rhinosurgical procedures. MATERIALS AND METHODS: We conducted a
      prospective cohort study of nasal airway function in consecutive Le Fort I
      osteotomy patients, who had not received simultaneous rhinosurgical procedures,
      between 2007 and 2008 at Kaiser Permanente Oakland Medical Center. We
      administered the Nasal Obstruction Symptom Evaluation (NOSE) survey before and 3
      months after surgery. Clinical and radiographic examinations were performed, and
      the relevant medical and demographic factors were analyzed. RESULTS: The initial
      study sample comprised 55 patients, of whom 5 were excluded. Of the remaining 50
      patients (median age 21 years, 60% women), the maxilla was advanced (median 4 mm,
      interquartile range 3 to 5) with minimal vertical change. During the follow-up
      period (median 5.5 months), significant improvement was seen in the NOSE scores
      for the cohort, with a median decrease of 10 units (P = .0005). Patients with
      moderate nasal obstruction (preoperative NOSE score >25) had the greatest
      improvement (P < .001). Those with severe nasal obstruction (preoperative NOSE
      score >50) improved, however, this did not reach statistical significance (P <
      .0625). The NOSE scores worsened in 10 patients; of these, 6 had minimal change.
      However, 4 had significant worsening, with 2 having symptomatic complaints. No
      predictor variables were identified in this small subgroup; however, individual
      case analyses revealed 1 subject with postoperative turbinate inflammation on the
      side of maxillary segmentalization and 1 had nasal septal buckling. CONCLUSIONS:
      Our overall findings have suggested that nasal airway function improved after
      maxillary advancement and that subjects with greater preoperative NOSE scores
      (>25) were more likely to experience relief of nasal obstructive symptoms.

PMID- 22883319
TI  - Oral teratomas: a report of 5 cases.
AB  - PURPOSE: To present a case series of 5 patients with oral teratomas, discussing
      the treatment and follow-up. REPORT OF CASES: Five patients (4 girls and 1 boy)
      with oral teratomas presented at the Maxillofacial Surgery Department of a
      University Hospital with a reference population of 1,000,000 between 1980 and
      2002. The associated lesions, clinical examination, histopathology, treatment and
      follow-up were registered and described. The newborns presented associated
      congenital malformations such as cleft palate, bifid tongue, dorso-nasal fistula
      and nasal dermoid cyst. In all 5 cases the tumor mass was excised at its base
      with surrounding normal tissue under general anesthesia combining conventional
      and electric scalpels. Histological analysis resulted in different compositions
      of multiple tissues typical of teratomas. After a mean follow-up of 8 years no
      sign of tumor recurrence had been detected. CONCLUSION: Teratomas were a rare
      finding within a large population of newborn patients. Five tumors were excised
      and histologically diagnosed as teratomas. No recurrence occurred after 8 years
      of follow-up.

PMID- 22883320
TI  - Odontoma-associated tooth impaction: accurate diagnosis with simple methods? Case
      report and literature review.
AB  - Odontomas account for the largest fraction of odontogenic tumors and are frequent
      causes of tooth impaction. A case of a 13-year-old female patient with an
      odontoma-associated impaction of a mandibular molar is presented with a review of
      the literature. Preoperative planning involved simple and convenient methods such
      as clinical examination and panoramic radiography, which led to a diagnosis of
      complex odontoma and warranted surgical removal. The clinical diagnosis was
      confirmed histologically. Multidisciplinary consultation may enable the clinician
      to find the accurate diagnosis and appropriate therapy based on the clinical and
      radiographic appearance. Modern radiologic methods such as cone-beam computed
      tomography or computed tomography should be applied only for special cases, to
      decrease radiation.

PMID- 22883322
TI  - Resective surgical approach shows a high performance in the management of
      advanced cases of bisphosphonate-related osteonecrosis of the jaws: a
      retrospective survey of 347 cases.
AB  - PURPOSE: The aim of this study was to evaluate the results of the surgical
      treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a large
      cohort. MATERIALS AND METHODS: A retrospective cohort multicenter study was
      designed. Patients were enrolled if they were diagnosed with BRONJ and received
      operative treatment. Data on demographic, health status, perioperative, and
      surgical factors were collected retrospectively. The primary outcome variable was
      a change in BRONJ staging (improvement, worsening, or no change). Interventions
      were grouped by local debridement and resective surgery. Data were collected for
      other variables as cofactors. Univariate analysis and logistic regressions were
      then performed. RESULTS: Of the 347 BRONJ-affected subjects, 59% showed
      improvement, 30% showed no change, and 11% showed worsening. Improvement was
      observed in 49% of cases treated with local debridement and 68% of cases treated
      with resective surgery. Multivariate analysis indicated that maxillary location,
      resective surgery, and no additional corticosteroid treatment were associated
      with a positive outcome. CONCLUSIONS: Surgical treatment of BRONJ appeared to be
      more effective when resective procedures were performed. Nonetheless, other
      factors, such as the absence of symptoms and the types of drug administration,
      should be taken into account before clinical decisions are made.

PMID- 22883321
TI  - Use of platelet-rich fibrin and platelet-rich plasma in combination with fat
      graft: which is more effective during facial lipostructure?
AB  - PURPOSE: Fat grafts have always represented a challenge in inducing the necessary
      neoangiogenesis, which results in significant resorption. This study was designed
      to compare the efficiency of first- and second-generation platelet-rich plasmas
      (PRPs) combined with a fat graft during facial lipostructure surgery. METHODS AND
      MATERIALS: To address the research purpose, the investigators designed and
      implemented a double-blinded prospective clinical trial. The patients underwent
      bilateral facial lipostructure, a natural long-lasting method of filling and
      supporting the face using intricate layers of infiltrated autologous fat. The
      method involved the use of PRP on 1 side and platelet-rich fibrin (PRF) on the
      other side. The study population was composed of all patients presenting to the
      authors' department for the evaluation and management of facial contouring in the
      cheek and cheekbone areas from June 2008 through December 2010. The primary
      predictor variable was the type of combination (PRP/fat or PRF/fat). The outcome
      variables were the amount of resorption, which was estimated by comparing pre-
      and postsurgical photographic views, pain, edema, and bruising. The statistical
      evaluation of the findings was performed using SPSS software. Parametric tests (t
      test and Levene test) were used to compare the treatment efficacy and
      complications between the groups. RESULTS: Twenty-five patients (8 men and 17
      women) underwent bilateral facial lipostructure surgery in the cheek and
      cheekbone areas using PRP and PRF. One year after the operation, a slight
      esthetic asymmetry was noticeable, with greater average resorption on the PRP/fat
      side. CONCLUSIONS: This first comparative clinical study highlights the value of
      using concentrated platelets for adipocyte grafts. The results suggest that the
      combination of fat and PRF is more effective than the combination of fat and PRP
      in the context of facial lipostructure surgery.

PMID- 22883323
TI  - Avoiding and managing temporomandibular joint total joint replacement surgical
      site infections.
AB  - PURPOSE: Surgical site infections (SSIs) are rare complications after total joint
      replacement (TJR); however, should an SSI occur, the clinical and economic
      consequences can be significant. A Medicare 5% national sample administrative
      dataset was used to identify and longitudinally observe patients undergoing total
      knee TJR for deep infections and revision surgery. In 69,663 patients undergoing
      elective total knee TJR, 1,400 infections (2%) were identified. The infection
      incidence within 2 years of implantation was 1.55%. A recent retrospective survey
      of 2,476 temporomandibular joint (TMJ) alloplastic TJR cases involving 3,368
      joints reported that a 1.51% SSI rate occurred over a mean of 6 months
      postoperatively, with a range of 2 weeks to 12 years. This article discusses
      approaches to avoid and minimize TMJ TJR SSIs and recommends management options
      should early or late SSIs occur. MATERIALS AND METHODS: On the basis of a review
      of the orthopedic SSI literature, this article will discuss TMJ TJR SSI risk,
      prevention, and management from a number of perspectives, including preoperative
      patient risk assessment, preincision antibiotic prophylaxis, anesthesia and skin
      preparation protocols, intraoperative surgical technique and duration of surgery,
      and postoperative antibiotic and follow-up regimens. RESULT: Ways to avoid and
      manage potential risks for SSI in TMJ TJR cases are recommended. The diagnostic
      criteria and management protocols for both early- and late-occurring SSIs after
      TMJ TJR are recommended. CONCLUSIONS: The risk of SSI after TMJ TJR can be
      decreased with appropriate consideration to preoperative patient risk assessment;
      properly timed antibiotic prophylaxis; and intraoperative, postoperative, and
      postdischarge attention to detail.

PMID- 22883324
TI  - Neurovascular pathophysiology in cerebral ischemia, dementia and the ageing brain
      - current trends in basic, translational and clinical research.
AB  - The 7th International Symposium on Neuroprotection and Neurorepair was held from
      May 2nd to May 5th, 2012 in Potsdam, Germany. The symposium, which directly
      continues the successful Magdeburg meeting series, attracted over 330 colleagues
      from 29 countries to discuss recent findings and advances in the field. The focus
      of the 2012 symposium was widened from stroke and traumatic brain injury to
      neurodegenerative diseases, notably dementia, and more generally the ageing
      brain. Thereby, emphasis was given on neurovascular aspects of neurodegeneration
      and stroke including the blood-brain barrier, recent findings regarding the
      pathomechanism of Alzheimer's disease, and brain imaging approaches. In addition,
      neurobiochemical aspects of neuroprotection, the role of astrogliosis, the
      clinical progress of cell-based approaches as well as translational hurdles and
      opportunities were discussed in-depth. This review summarizes some of the most
      stimulating discussions and reports from the meeting.

PMID- 22883325
TI  - Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory
      disease: a mathematical modelling study.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) results from the ascending spread
      of microorganisms from the vagina and endocervix to the upper genital tract. PID
      can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of
      development of PID after the sexually transmitted bacterial infection Chlamydia
      trachomatis (chlamydia) might affect the impact of screening interventions, but
      is currently unknown. This study investigates three hypothetical processes for
      the timing of progression: at the start, at the end, or throughout the duration
      of chlamydia infection. METHODS: We develop a compartmental model that describes
      the trial structure of a published randomised controlled trial (RCT) and allows
      each of the three processes to be examined using the same model structure. The
      RCT estimated the effect of a single chlamydia screening test on the cumulative
      incidence of PID up to one year later. The fraction of chlamydia infected women
      who progress to PID is obtained for each hypothetical process by the maximum
      likelihood method using the results of the RCT. RESULTS: The predicted cumulative
      incidence of PID cases from all causes after one year depends on the fraction of
      chlamydia infected women that progresses to PID and on the type of progression.
      Progression at a constant rate from a chlamydia infection to PID or at the end of
      the infection was compatible with the findings of the RCT. The corresponding
      estimated fraction of chlamydia infected women that develops PID is 10% (95%
      confidence interval 7-13%) in both processes. CONCLUSIONS: The findings of this
      study suggest that clinical PID can occur throughout the course of a chlamydia
      infection, which will leave a window of opportunity for screening to prevent PID.

PMID- 22883327
TI  - [Atrial fibrillation-related stroke: a novel focus in stroke study].

PMID- 22883326
TI  - [Pay attention to the preventive researches for chronic elderly disabling
      diseases].

PMID- 22883328
TI  - [Enhance the clinical knowledge of cerebral cortical venous thrombosis].

PMID- 22883329
TI  - [Acute ischemic stroke in the very elderly outcome and predictive factors].
AB  - OBJECTIVE: To investigate the clinical characteristics, 3-month outcome and
      predictive factors in the very elderly patients with ischemic stroke. METHODS: A
      total of 305 acute ischemic patients aged 65 years and over were enrolled in the
      study. They were divided into two subgroups by age: 80 years old and over (n =
      78), 65 - 79 years old (n = 227). The clinical outcome was assessed by the
      modified Rankin Scale (mRS) on (90 +/- 7) days after stroke, and categorized as
      good (scoring 0 - 2) or poor (scoring 3 - 6) outcome. RESULTS: Significantly
      lower BMI [(23.62 +/- 4.92) kg/m(2) vs (25.08 +/- 3.69) kg/m(2), P = 0.005],
      lower frequency of dyslipidemia (56.41% vs 71.13%, P = 0.006) and alcohol intake
      (0% vs 6.61%, P = 0.043) were found in the very elderly group. The rates of poor
      functional outcome in the >= 80 years group and the 65 - 79 years old group were
      56.41% (44/76) and 41.40% (94/224) respectively, with a P value of 0.015.
      Multivariate logistic regression analysis showed that higher National Institute
      of Health stroke scale (NIHSS) total score (OR 1.48, 95%CI 1.19 - 1.83) and lower
      albumin level (OR 0.73, 95%CI 0.55 - 0.95) were associated with poor outcome in
      >= 80 year old, whereas higher NIHSS total score (OR 1.38, 95%CI 1.24 - 1.53) and
      complications during hospital stay (OR 2.58, 95%CI 1.07 - 6.19) were predictive
      factors in the 65 - 79 years old group. CONCLUSION: Our study suggests that NIHSS
      scores, albumin level and complications during hospitalization are useful
      predictive factors for the short-term poor functional outcome in the patients of
      >= 65 years old and >= 80 years old patients have a worse prognosis.

PMID- 22883330
TI  - [Clinical diagnosis and analysis of cerebral cortical venous thrombosis].
AB  - OBJECTIVE: To investigate the clinical and radiological characteristics of
      cortical vein thrombosis for early diagnosis and treatment. METHODS:
      Retrospective analysis was carried out with the clinical cases of cortical vein
      thrombosis in 2010. The symptoms, sign, neuroimaging were analyzed and related
      literatures were reviewed. RESULTS: Four patients were collected, average age was
      forty years old. The main symptoms were headache and focal neurological signs in
      varying degrees, infarction or hemorrhage in one or two sides of parietal lobe
      could be found in CT or MRI. Hemorrhage was found in two patients, infarction was
      found in one patient, hemorrhage and infarction were both found in another
      patient. CONCLUSIONS: Headache and focal neurological signs are the common sings
      and symptoms of patients with cortical vein thrombosis. CT and MRI are effective
      methods for the diagnosis of cortical vein thrombosis.

PMID- 22883331
TI  - [An etiological analysis of 367 neurological outpatients with complaint of
      vertigo].
AB  - OBJECTIVE: To explore the etiology of patients with chief complaint of vertigo in
      the department of neurology in order to reduce the rate of misdiagnosis. METHODS:
      A total of 367 patients with chief complaint of vertigo in our department of
      neurology were followed up. The associated medical history, symptoms and physical
      examination were obtained. RESULTS: The main diagnoses for the 367 patients were
      benign paroxysmal positional vertigo (BPPV) (219, 59.7%), posterior circulation
      ischemia (PCI) (65, 17.7%), migraine (31, 8.4%), hypertension (18, 4.9%) and
      psychogenic vertigo (17, 4.6%). CONCLUSIONS: Presentation of vertigo can be
      clinically diagnosed in most diseases, with the most common cause of BPPV.
      Combination of the prominent clinical features, physical examinations and
      especially Dix-Hallpike maneuver may guide the general physicians to a most
      proper cause of vertigo.

PMID- 22883332
TI  - [The B lymphocytes D8/17 antigen expression and characteristics of patients with
      rheumatic heart disease in Guangdong].
AB  - OBJECTIVE: To investigate the D8/17 antigen expression of patients with rheumatic
      heart disease (RHD) in Guangdong province and study the antigen's
      characteristics. METHODS: The level of D8/17 antigen expression on B lymphocytes
      was determined with flow cytometry assay in 96 RHD patients and 83 unaffected
      controls. The percentage of B-cells expressing the D8/17 antigen having more than
      10% was considered to be positive. D8/17 antigen was extracted by
      immunoprecipitation, and the antigen characteristics was analyzed by tandem mass
      spectrometry. RESULTS: The mean percentage of B-cells expressing the D8/17
      antigen was (85.36 +/- 15.15)% in the RHD patients and (82.89 +/- 4.55)% in the
      controls, with no significant difference between the two groups (P = 0.436).
      Moreover, the positive rate of the D8/17 expression was 100% in either the RHD
      patients or the controls. The molecular weight of D8/17 antigen was found to be
      40 000 - 67 000, and the purified protein was most likely to match moesin or beta
      actin. CONCLUSIONS: B-cell antigen D8/17 is not associated with RHD in Guangdong
      province of China. Moesin or beta-actin is the most likely protein to match D8/17
      antigen.

PMID- 22883333
TI  - [The relationship between sleep quality and glucose level, diabetic complications
      in elderly type 2 diabetes mellitus].
AB  - OBJECTIVE: To explore the relationship between sleep quality and glucose level,
      diabetic complications in elderly type 2 diabetes mellitus. METHODS: A total of
      130 hospitalized elderly type 2 diabetes in our hospital were included in the
      study. Questionnaires and other related clinical data were collected within one
      week after admission. Patients were divided into two groups: poor-sleeper group
      and good-sleeper group according to Pittsburgh Sleep Quality Index (PSQI).
      RESULTS: Sixty percent (78/130) of these patients were poor sleepers. The
      following parameters differed in the two groups: the duration of diabetes [(7.9
      +/- 1.8) years vs (7.2 +/- 1.5) years, t = 2.318], systolic blood pressure [(148
      +/- 30) mm Hg (1 mm Hg = 0.133 kPa) vs (138 +/- 23) mm Hg, t = 2.037], fasting
      plasma glucose (FPG) [(10.7 +/- 2.2) mmol/L vs (9.8 +/- 1.9) mmol/L, t = 2.410],
      hemoglobin A1c (HbA1c) [(8.6 +/- 2.2)% vs (7.8 +/- 2.1)%, t = 2.068], high
      sensitive C-reactive protein (hs-CRP) [(5.27 +/- 2.34) mg/L vs (4.44 +/- 1.76)
      mg/L, t = 2.179], ratio of diabetic complications (61% vs 32%, chi(2) = 4.257),
      percentage of depression (20% vs 8%, chi(2) = 3.722), score of life quality [(98
      +/- 19) scores vs (89 +/- 13) scores, t = 2.980], and proportion of patients
      treated with insulin (32% vs 12%, chi(2) = 4.489). All the above parameters were
      significantly higher in poor-sleeper group than the good-sleeper group (all P
      value < 0.05). Multiple correlation analysis showed that the factors affecting
      sleep quality were FPG, HbA1c, duration of diabetes, diabetic complications,
      depression, life quality and insulin application (r = 0.213, 0.257, 0.223, 0.335,
      0.422, 0.3451, 0.231, respectively; all P value < 0.05). By multivariate logistic
      regression analysis, the followings were found: FPG (beta = 1.29, P < 0.05) and
      PSQI (beta = 1.07, P < 0.05) were found to be correlated with HbA1c. With
      increasing of PSQI, FPG, HbA1c, diabetic complications and life quality were
      changed significantly (all P value < 0.05). The independent risk factors of
      diabetic complications were duration of diabetes (OR = 1.32, 95%CI 1.01 - 2.01),
      HbA1c (OR = 2.01, 95%CI 1.63 - 2.67), hs-CRP (OR = 1.12, 95%CI 1.08 - 1.21) and
      PSQI (OR = 1.71, 95%CI 1.58 - 2.02). CONCLUSIONS: Elderly type 2 diabetes
      mellitus are usually poor sleepers. Sleep quality probably affects blood glucose
      regulation, and is closely correlated with the occurrence of complications. In
      addition, poor sleep quality results in poor life quality.

PMID- 22883334
TI  - [The diagnostic significance of nailfold video-capillaroscopy in systemic
      sclerosis].
AB  - OBJECTIVE: To observe nailfold capillary changes in a cohort of connective tissue
      disease (CTD) with Raynaud's phenomenon (RP) and to explore the diagnostic value
      of nailfold video-capillaroscopy (NVC) in systemic sclerosis (SSc). METHODS:
      Sixty CTD patients with RP divided into SSc group (n = 36) and non-SSc group (n =
      24) were referred to an experienced operator for NVC. RESULTS: The patients had
      decreased capillary loops in SSc group with the capillary diameter more enlarged
      in SSc group than non-SSc group. The number of patients in SSc group with giant
      capillaries was 14, while 3 in non-SSc group. There were 23 patients with
      haemorrhages in SSc group and 9 in non-SSc group. The number of patients with
      severe effusion was 15 in SSc group, while 2 in non-SSc group. By using the ROC
      curves, indexes with AUC at least 0.7 of the input capillary diameter, the output
      capillary diameter, the middle capillary diameter, blood color and effusion for
      the diagnostic cutoff points were 18.5 um, 24.5 um, 19.5um, deep red and severe
      effusion. With at least 2 out of the top 3 indexes, the diagnostic sensitivity
      and specificity of SSc were higher. CONCLUSIONS: CTD Patients with RP of SSc have
      less capillary loops, more enlarged capillaries, more giant capillaries, more
      severe effusion and more haemorrhages than non-SSc patients. The characteristics
      of nailfold capillary changes in SSc patients with RP can be helpful for the
      diagnosis and the differential diagnosis of SSc.

PMID- 22883335
TI  - [The microbiological and clinical analysis of bloodstream infections with
      identifiable sources].
AB  - OBJECTIVE: To evaluate the microbial spectrum and clinical characteristics of
      microbiological diagnosed bloodstream infections (BSI) with identified infective
      sources. METHODS: The hospitalized patients microbiologically diagnosed as BSI
      with identified infective sources were included in this study from January 2008
      to December 2009. Data were collected retrospectively and analyzed by software
      SPSS 17.0. RESULTS: In this 2-year study, 301 strains of microbes were isolated
      from 249 patients. There were 205 (82.33%) patients with monomicrobial BSI, while
      the other 44 (17.67%) patients with polymicrobial BSI. The most common identified
      source of bloodstream infections was lower respiratory tract infection (125,
      41.5%), followed by intraabdominal infection (55, 18.3%) and intravascular
      devices related infection (54, 17.9%). The four most common isolated pathogens
      were Acinetobacter species (60, 19.9%), Escherichia coli (50, 16.6%), Pseudomonas
      species (35, 11.6%) and Staphylococcus Aureus (34, 11.3%). Eighty-eight (35.3%)
      patients died during hospitalization due to all causes, out of which 62 (24.9%)
      patients died owing to BSI. The patients with BSI originated from lower
      respiratory tract had a higher crude in-hospital case-fatality ratio than those
      with BSI originated from other resources (OR = 2.186; 95%CI 1.260 - 3.792; chi(2)
      = 7.879, P = 0.005). In the multivariate regression, age >= 65, invasive
      mechanical ventilation, reservation of central line and polymicrobial BSI during
      hospitalization were independent risk factors of death due to all causes.
      CONCLUSIONS: Lower respiratory tract is the most common originated source of BSI
      with microbiological identified sources. Gram-negative bacillus taking advantage,
      the microbial spectrum of BSI with identified sources in our study is different
      from those reported before both in primary and secondary BSI. The patients with
      BSI originated from respiratory tract have a higher crude in-hospital case
      fatality ratio.

PMID- 22883336
TI  - [Quantitative monitoring of blood cytomegalovirus after allogeneic hematopoietic
      stem cell transplantation and its clinical significance].
AB  - OBJECTIVE: To investigate the risk factor for cytomegalovirus (CMV) viremia and
      its impact on the survival of patients after allogeneic hematological stem cell
      transplantation (allo-HSCT). METHODS: Quantitative fluorescence PCR was used to
      examine the quantity of CMV in mononuclear cells. All patients were tested weekly
      after allo-HSCT within 3 months. Univariate and multivariate analysis were used
      to determine the risk factors of CMV viremia. Five-year overall survival rate was
      compared and analyzed between the patients with or without CMV viremia. RESULTS:
      The incidence of CMV viremia was 72.1% (132/183). Of which, 59.1% (78/132)
      occurred post one month after transplantation, 40.9% (54/132) occurred within one
      month and 27.9% (51/183) sustained negative within three months. Two cases were
      clearly diagnosed as CMV disease with a incidence of 1.1%. Both univariate and
      multivariate analysis indicated that transplant methods and blood cyclosporine A
      (CsA) concentration were significantly correlated with CMV viremia. When pairwise
      compared the results between the different transplant methods, significant
      differences of CMV viremia were found between human leukocyte antigen (HLA)
      matched sibling and HLA mismatched relatives, unrelative donor or cord blood (all
      P values < 0.05). There was no significant difference between HLA mismatched
      relatives and unrelative donor or cord blood. Further analysis showed that the
      incidence of CMV viremia was much higher in those who had used antithymocyte
      globulin (ATG) then those not used ATG. The Kaplan-Meier survival curve showed
      there was no significant difference between the groups with and without CMV
      viremia. CONCLUSIONS: The incidence of CMV viremia after allo-HSCT is 72.1%.
      Administration of ATG during conditioning regimen and blood CsA concentration >
      300 ug/L are the main risk factors for CMV viremia. There is no significant
      effect of CMV viremia on the cumulative overall survival, while prompt treatment
      of CMV viremia is a crucial way to prevent CMV disease.

PMID- 22883337
TI  - [The efficacy of etanercept in enthesitis in ankylosing spondylitis and an
      evaluation method for enthesitis].
AB  - OBJECTIVE: To evaluate the efficacy of etanercept in the treatment of active
      ankylosing spondylitis (AS) with enthesitis and explore an easy and accurate
      scoring method. METHODS: We designed this 12-week double-blind, placebo
      controlled, randomized clinical study in active AS patients. The first part was a
      6-week placebo-controlled period that patients received etanercept or placebo,
      followed by a 6-week open-label period that all patients received etanercept. At
      week 0, 2, 4, 6, 8, 10, 12, the scores of enthesitis were recorded. The primary
      efficacy endpoint was the Mander Index in the two groups. We compared the
      Maastricht AS Enthesis Score (MASES) index, Spondyloarthritis Research Consortium
      of Canada (SPARCC) index, Berlin index and San Francisco index with the Mander
      Index. RESULTS: A total of 127 patients were included with 92 in the etanercept
      group and 35 in the placebo group. In etanercept group there were 25, 41, 47
      patients without enthesitis at week 2, 4, 6 separately. At week 12, more than 70%
      patients' enthesitis in two groups turned negative. The primary endpoint, as the
      Mander Index at week 6, was achieved by 0(0, 2) score in the etanercept group
      compared with 1(0, 3) score in the placebo group (P = 0.0286). Among the four
      Indexes, the San Francisco Index was the one most correlated with the Mander
      Index. CONCLUSION: Etanercept can improve the symptoms of enthesitis fast and
      significantly. In clinics, the San Francisco Index is easier to operate and more
      accurate for assessment.

PMID- 22883338
TI  - [A preliminary report of apoA5 gene novel receptor-binding domain mutation in a
      patient with severe hypertriglyceridemia].
AB  - OBJECTIVE: To find novel variants and explore potential mechanism of triglyceride
      metabolism by resequencing apoA5 gene in patients with severe
      hypertriglyceridemia. METHODS: The apoA5 gene in the patients with severe
      hypertriglyceridemia were resequenced, who had been excluded with variants in LPL
      or apoCII. With constructed apoA5 cDNA expression vectors, transiently expression
      was observed in vitro and the protein expression was detected by Western blot and
      (35)S-labeled immunoprecipitation. RESULTS: The mutations of T184S and V153M were
      found in a patient with heterozygous variants in apoA5, and T184S was not
      reported before. Both mutant and wild type apoA5 cDNA expression vectors were
      constructed successfully. Western blot and immunoprecipitation showed they can be
      expressed in the cell and the mutational apoA5 can be secreted from the cell as
      well as wild type. CONCLUSION: A novel mutation in apoA5 was found in a patient
      with severe hypertriglyceridemia, which has the potential damaging effect for the
      function of this protein but not the secretion function. It need further study on
      the interaction of apoA5 and other related proteins.

PMID- 22883339
TI  - [The potential pathogenesis of gastrointestinal vascular malformation and the
      potential mechanism of thalidomide in the treatment of gastrointestinal vascular
      malformation].
AB  - OBJECTIVE: To study the pathogenesis of gastrointestinal vascular malformation
      (GIVM) and the potential mechanism of thalidomide in the treatment of
      gastrointestinal bleeding due to GIVM. METHODS: We collected the surgical
      intestinal specimens from 10 patients who suffered from massive hemorrhage of
      gastrointestinal tract owning to GIVM and the normal intestinal mucosa around the
      lesions, as well as normal intestinal mucosa from healthy subjects.
      Immunohistochemical (IHC) staining was carried out to investigate the differences
      of angiopoietin 2 (Ang2), Notch1 and delta like ligand 4 (Dll4) in the above
      three intestinal mucosa to find the relationship with the pathogenesis of GIVM.
      Human umbilical vein endothelial cells (HUVECs) were cultured with 0, 25, 50, 100
      and 200 mg/L thalidomide for 24 or 48 hours to observe their mRNA and protein
      expressions of Ang2, Notch1, Dll4 by real-time PCR and Western blot. RESULTS: By
      IHC staining, more expressions of Ang2, Notch1 and Dll4 in the lesions were
      detected than those in the normal intestinal mucosa around the lesions and the
      normal intestinal mucosa in healthy people. The expressions of Ang2, Notch1 and
      Dll4 were significantly correlated (P = 0.016, r = 0.732), and the expressions of
      Notch1 and Dll4 were absolutely correlated (P = 0.000, r = 1.000). Real-time PCR
      and Western blot showed that thalidomide could down-regulate the expressions of
      them, which were in a concentration-dependent manner. CONCLUSION: Ang2, Notch1
      and Dll4 may correlate with the pathogenesis of GIVM, while thalidomide can
      concentration-dependently down-regulate the expression of Ang2, Notch1 and Dll4,
      which may be one of the mechanism that thalidomide play a therapeutic role in
      GIVM.

PMID- 22883340
TI  - [The role of hypermethylation in promoter region of ubiquitin carboxyl-terminal
      hydrolase L1 in human esophageal cancer].
AB  - OBJECTIVE: To study the association of ubiquitin carboxyl-terminal hydrolase L1
      (UCHL1) promoter region methylation with human esophageal cancer. METHODS:
      Promoter region methylation of UCHL1 was detected by methylation specific PCR
      (MSP) in esophageal cancer cell lines and tissue samples. The expression of UCHL1
      was detected by semi-quantitative RT-PCR and Western blot in esophageal cancer
      cell lines. 5-Aza-2'-deoxycytidine (5-Aza) was applied to reactivate methylated
      cell lines. RESULTS: Complete methylation of UCHL1 promoter region was detected
      in 8 cell lines (KYSE30, KYSE150, KYSE140, KYSE450, KYSE510, TE3, TE7, TE10).
      Loss of UCHL1 expression was found in 7 cell lines (KYSE30, KYSE150, KYSE140,
      KYSE450, KYSE510, TE3, TE7). Reduced expression was found in TE10 cell line.
      Promoter region hypermethylation was correlated with UCHL1 expression in
      esophageal cancer cell lines. Re-expression of UCHL1 was induced by 5-Aza
      treatment in KYSE150 and TE3 cell lines. UCHL1 was frequently methylated in human
      primary esophageal cancer (74.51%, 38/51), while no methylation was detected in
      normal esophageal mucosa(0/10). No association was found between promoter region
      methylation and age, gender, tumor location, tumor stage or lymph node
      metastasis. CONCLUSIONS: UCHL1 is silenced by promoter region hypermethylation in
      human esophageal cancer. Methylation of UCHL1 is frequently happened to primary
      esophageal cancer and may play an important role in the tumorigenesis.

PMID- 22883341
TI  - Let's help parents help themselves: a letter to the editor supporting the safety
      of behavioural sleep techniques.

PMID- 22883342
TI  - Forty years of increasing suicide mortality in Poland: undercounting amidst a
      hanging epidemic?
AB  - BACKGROUND: Suicide rate trends for Poland, one of the most populous countries in
      Europe, are not well documented. Moreover, the quality of the official Polish
      suicide statistics is unknown and requires in-depth investigation. METHODS:
      Population and mortality data disaggregated by sex, age, manner, and cause were
      obtained from the Polish Central Statistics Office for the period 1970-2009.
      Suicides and deaths categorized as 'undetermined injury intent,' 'unknown
      causes,' and 'unintentional poisonings' were analyzed to estimate the reliability
      and sensitivity of suicide certification in Poland over three periods covered by
      ICD-8, ICD-9 and ICD-10, respectively. Time trends were assessed by the Spearman
      test for trend. RESULTS: The official suicide rate increased by 51.3% in Poland
      between 1970 and 2009. There was an increasing excess suicide rate for males,
      culminating in a male-to-female ratio of 7:1. The dominant method, hanging,
      comprised 90% of all suicides by 2009. Factoring in deaths of undetermined intent
      only, estimated sensitivity of suicide certification was 77% overall, but lower
      for females than males. Not increasing linearly with age, the suicide rate peaked
      at ages 40-54 years. CONCLUSION: The suicide rate is increasing in Poland, which
      calls for a national prevention initiative. Hangings are the predominant suicide
      method based on official registration. However, suicide among females appears
      grossly underestimated given their lower estimated sensitivity of suicide
      certification, greater use of "soft" suicide methods, and the very high 7:1 male
      to-female rate ratio. Changes in the ICD classification system resulted in a
      temporary suicide data blackout in 1980-1982, and significant modifications of
      the death categories of senility and unknown causes, after 1997, suggest the need
      for data quality surveillance.

PMID- 22883343
TI  - Four-dimensional measurement of the displacement of metal clips or postoperative
      surgical staples during 320-multislice computed tomography scanning of gastric
      cancer.
AB  - PURPOSE: To investigate the respiratory motion of metal clips or surgical staples
      placed in the gastric wall for planning of radiation therapy in gastric cancer
      patients. METHODS: This study examined 15 metal markers in the gastric walls of
      12 patients with gastric cancer treated with external-beam photon RT. Motion
      assessment was analyzed in 41 respiratory phases covering 20 s acquired with
      computed tomography (CT) in the RT position using 320-multislice CT. The intra
      fraction displacement was assessed in the cranio-caudal (CC), antero-posterior
      (AP), and right-left (RL) directions. RESULTS: Motion in the CC direction showed
      a very strong correlation (R2 > 0.7) with the respiratory curve in all 15
      markers. The mean (+/- SD) intra-fractional gastric motion (maximum range of
      displacement) was 12.5 (+/- 3.4) mm in the CC, 8.3 (+/- 2.2) mm in the AP, and
      5.5 (+/- 3.0) mm in the RL direction. No significant differences in magnitude of
      motion were detected in the following: a) among the upper (n = 6), middle (n =
      4), and lower (n = 5) stomach regions; b) between metal clips (n = 5) and
      surgical staples (n = 10); and c) between full (n = 9) and empty (n = 6)
      stomachs. CONCLUSIONS: Motion in primary gastric tumor was evaluated with 320
      multislice CT. According to this study, the 95th percentile values from the
      cumulative distributions of the RL, AP, and CC direction were 6.3 mm, 9.0 mm, and
      13.6 mm, respectively.

PMID- 22883344
TI  - Comparison of corneal thickness and curvature in myopic and keratoconic eyes of
      patients from French Caribbean Isles and continental France.
AB  - PURPOSE: To evaluate the corneal thickness and curvature of myopic and patients
      with keratoconus from two countries. METHODS: This cross-sectional study was
      conducted at Cabinet Opale, Fort de France, French West Indies and University
      Hospital of Bordeaux, France. Corneal thickness and curvature were assessed in
      170 keratoconic eyes of 89 residents of the French Caribbean Islands (FCI) and
      159 keratoconic eyes of 91 residents of the Aquitaine region of southwest France.
      A group of age-matched keratoconus-free patients who had been referred for
      refractive surgery owing to myopia (173 FCI [173 eyes; 87 individuals] and
      Aquitaine [181 eyes; 93 individuals]) were also assessed. RESULTS: The mean age
      at keratoconus diagnosis was significantly higher among FCI than Aquitaine
      residents (p = 0.009). The mean keratometric (Km) reading was statistically
      higher for keratoconic FCI than Aquitaine patients, at 48.06 versus 46.21
      diopters (p = 0.001). This difference was more pronounced among patients aged >40
      years than those <=40 years (p = 0.009). Patients with keratoconus showed no
      significant difference in mean central corneal thickness and thinnest corneal
      point values, irrespective of region. Myopic individuals from the FCI, however,
      had significantly lower mean central corneal thickness and thinnest corneal point
      measurements than Aquitaine myopics, irrespective of age group (p <= 0.0008).
      CONCLUSION: The corneas of patients with keratoconus of African-Caribbean and
      Caucasian origins are of similar thickness. Myopic African-Caribbean patients
      referred for refractive surgery tend to present with thinner corneas than
      Caucasians.

PMID- 22883345
TI  - Monogenic forms of systemic lupus erythematosus: new insights into SLE
      pathogenesis.
AB  - The pathogenesis of Systemic Lupus Erythematosus (SLE) is complex and remains
      poorly understood. Infectious triggers, genetic background, immunological
      abnormalities and environmental factors are all supposed to interact for the
      disease development. Familial SLE as well as early-onset juvenile SLE studies
      make it possible to identify monogenic causes of SLE. Identification of these
      rare inherited conditions is of great interest to understand both SLE
      pathogenesis and molecular human tolerance mechanisms. Complement deficiencies,
      genetic overproduction of interferon-alpha and apoptosis defects are the main
      situations that can lead to monogenic SLE.Here, we review the different genes
      involved in monogenic SLE and highlight their importance in SLE pathogenesis.

PMID- 22883346
TI  - Diagnosis and management of tuberculosis in transplant donors: a donor-derived
      infections consensus conference report.
AB  - Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the
      world's population. In previous decades, access to organ transplantation was
      restricted to academic medical centers in more developed, low tuberculosis (TB)
      incidence countries. Globalization, changing immigration patterns, and the
      expansion of sophisticated medical procedures to medium and high TB incidence
      countries have made tuberculosis an increasingly important posttransplant
      infectious disease. Tuberculosis is now one of the most common bacterial causes
      of solid-organ transplant donor-derived infection reported in transplant
      recipients in the United States. Recognition of latent or undiagnosed active TB
      in the potential organ donor is critical to prevent emergence of disease in the
      recipient posttransplant. Donor-derived tuberculosis after transplantation is
      associated with significant morbidity and mortality, which can best be prevented
      through careful screening and targeted treatment. To address this growing
      challenge and provide recommendations, an expert international working group was
      assembled including specialists in transplant infectious diseases, transplant
      surgery, organ procurement and TB epidemiology, diagnostics and management. This
      working group reviewed the currently available data to formulate consensus
      recommendations for screening and management of TB in organ donors.

PMID- 22883347
TI  - Tetralogy of Fallot with complete DiGeorge syndrome: report of a case and a
      review of the literature.
AB  - Complete DiGeorge syndrome (CDGS) has a severe T-cell immunodeficiency and is
      fatal without thymus or bone marrow transplantation. Associated congenital heart
      disease (CHD) further complicates the clinical management. We report an infant
      with tetralogy of Fallot, confluent and hypoplastic pulmonary arteries, right
      aortic arch, and aberrant left subclavian artery. He was athymic with no CD3+ T
      cells. CDGS was diagnosed with 22q11.2 deletion. The patient underwent central
      aortopulmonary shunt at 12 days of age. The patient died at 5 weeks of age
      awaiting thymus transplantation. We performed a review of the literature
      regarding CDGS and CHD. We found 43 cases including conotruncal defects (20) and
      nonconotruncal defects (23). The overall mortality rate was 67%. Among 30 cases
      undergoing transplantation (bone marrow 16 and thymus 12, bone marrow + thymus
      2), the mortality rate was 53%. The patients with conotruncal defects were more
      likely to die before transplantation (45% vs. 16%, P =.04). The main cause of
      death was infection before and after transplantation. We conclude that children
      with CDGS and CHD have a high mortality. Bone marrow and thymus transplantation
      can improve the survival, but the overall management of these high risk patients
      remains challenging. 

PMID- 22883348
TI  - Using principal component analysis to describe the Apert skull deformity and
      simulate its correction.

PMID- 22883349
TI  - Ageing and taste.
AB  - Taste perception has been studied frequently in young and older adult groups.
      This paper systematically reviews these studies to determine the effect of ageing
      on taste perception and establish the reported extent of sensory decline. Five
      databases were searched from 1900 to April 2012. Articles relating to healthy
      ageing in human subjects were included, reviewed and rated (Downs and Black
      scoring system). Sixty-nine studies investigated the effect of ageing on taste
      perception; forty examined detection thresholds of which twenty-three provided
      sufficient data for meta-analysis, eighteen reported identification thresholds
      and twenty-five considered supra-threshold intensity perception. Researchers
      investigating detection thresholds considered between one and thirteen taste
      compounds per paper. Overall, the consensus was that taste detection thresholds
      increased with age (Hedges' g = 0.91, P < 0.001), across all taste modalities.
      Identification thresholds were reported to be higher for older adults in
      seventeen out of eighteen studies. Sixteen out of twenty-five studies reported
      perception of taste intensity at supra-threshold levels to be significantly lower
      for older adults. However, six out of nine studies concerning sucrose found
      perceived intensity of sweet taste not to diminish with age. The findings of this
      systematic review suggest taste perception declines during the healthy ageing
      process, although the extent of decline varies between studies. Overall, the
      studies reviewed had low Downs and Black scores (mean 16 (SD 2)) highlighting the
      need for more robust large scale and longitudinal studies monitoring the impact
      of ageing on the sensory system, and how this influences the perception of foods
      and beverages.

PMID- 22883351
TI  - Viruses: foe, freeloader or friend?

PMID- 22883350
TI  - Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa
      miR-137.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that mainly function as negative
      regulators of gene expression (Lai, 2002) and have been shown to be involved in
      schizophrenia etiology through genetic and expression studies (Burmistrova et
      al., 2007; Hansen et al., 2007a; Perkins et al., 2007; Beveridge et al., 2010;
      Kim et al., 2010). In a mega analysis of genome-wide association study (GWAS) of
      schizophrenia (SZ) and bipolar disorders (BP), a polymorphism (rs1625579) located
      in the primary transcript of a miRNA gene, hsa-miR-137, was reported to be
      strongly associated with SZ. Four SZ loci (CACNA1C, TCF4, CSMD1, C10orf26)
      achieving genome-wide significance in the same study were predicted and later
      experimentally validated (Kwon et al., 2011) as hsa-miR-137 targets. Here, using
      in silico, cellular and luciferase based approaches we also provide evidence that
      another well replicated candidate schizophrenia gene, ZNF804A, is also target for
      hsa-miR-137.

PMID- 22883352
TI  - The epidemiological and public health research response to 2009 pandemic
      influenza A(H1N1): experiences from Hong Kong.
AB  - In recent years, Hong Kong has invested in research infrastructure to
      appropriately respond to novel infectious disease epidemics. Research from Hong
      Kong made a strong contribution to the international response to the 2009
      influenza A (H1N1) pandemic (pH1N1). Summarizing, describing, and reviewing Hong
      Kong's response to the 2009 pandemic, this article aimed to identify key elements
      of a real-time research response. A systematic search in PubMed and EMBASE for
      research into the infection dynamics and natural history, impact, or control of
      pH1N1 in Hong Kong. Eligible articles were analyzed according to their scope.
      Fifty-five articles were included in the review. Transmissibility of pH1N1 was
      similar in Hong Kong to elsewhere, and only a small fraction of infections were
      associated with severe disease. School closures were effective in reducing pH1N1
      transmission, oseltamivir was effective for treatment of severe cases while
      convalescent plasma therapy has the potential to mitigate future pandemics. There
      was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing
      important information on the epidemiology of the novel virus with relevance
      internationally as well as locally. The scientific knowledge gained through these
      detailed studies of pH1N1 is now being used to revise and update pandemic plans.
      The experiences of the research response in Hong Kong could provide a template
      for the research response to future emerging and reemerging disease epidemics.

PMID- 22883353
TI  - Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met
      polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in
      Japanese patients with major depressive disorder (MDD).
AB  - OBJECT: We investigated an association between the polymorphism of brain-derived
      neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in
      Japanese patients with major depressive disorder (MDD). We also examined
      mirtazapine's effects on the serum BDNF and plasma levels of catecholamine
      metabolites in these patients. METHODS: Eighty-four patients who met the DSM-IV
      TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF
      Val66Met polymorphism was detected by direct sequencing in the region, and serum
      BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA
      and HPLC-ECD, respectively. RESULTS: Mirtazapine treatment for 4 weeks
      significantly increased serum BDNF levels in the responders, whereas
      nonresponders showed significant decreases. No association was found between
      either of the two genotypes (Val/Val vs. Met-carriers) and the response to
      mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the
      plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol
      (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of
      HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met
      polymorphism in patients with depression is, however, associated with neither a
      particular response to mirtazapine treatment nor baseline serum BDNF levels.
      CONCLUSION: Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF
      Val66Met polymorphism are related to the mirtazapine response in MDD.

PMID- 22883354
TI  - Molar incisor hypomineralisation: possible aetiological factors in children from
      urban and rural areas.
AB  - AIM: To analyse factors potentially associated with molar incisor
      hypomineralisation (MIH) development. METH!ODS: A population-based study was
      carried out with 903 children aged from 6-12 years old, born and residing in
      rural and urban areas of the town of Botelhos, State of Minas Gerais, Brazil.
      Their mothers completed a structured medical history questionnaire, from
      pregnancy to the child's 3rd year of life. Two examiners evaluated children for
      MIH according to criteria suggested by the European Academy of Paediatric
      Dentistry. Descriptive analyses of the data and odds ratios (OR) with 95% test
      based confidence intervals (CI) were estimated. Chi-square test was used to
      evaluate the differences between groups. RESULTS: The prevalence of MIH in
      children from rural area (RA) was significantly higher than those from the urban
      area (UA) (24.9% versus 17.8%, p= 0.01). In urban children, neither significant
      associations with MIH nor medical problems were found. In rural children,
      however, MIH was significantly more common among those whose mothers had
      experienced medical problems during pregnancy (OR=2.11; 1.01-4.37 CI 95%;
      p=0.04), who had throat infections (OR=2.93; 1.47-5.87 CI 95%; p=0.01), who had
      high fever (OR=1.91; 1.07-3.39 CI 95%; p=0.02), and who had used amoxicillin
      associated with other antibiotics (OR=1.92; 1.02-3.62 CI 95%; p=0.04) during the
      first 3 years of life. CONCLUSION: This study suggests a link between MIH and
      health problems during pregnancy, as well as environmental factors.

PMID- 22883355
TI  - Trends of oral health care and dental treatment needs in relation to molar
      incisor hypomineralisation defects: a study amongst a group of Iraqi
      schoolchildren.
AB  - BACKGROUND: The dynamic properties of molar-incisor-hypomineralisation lesions
      (MIH) may impact negatively on personal daily oral care resulting in increased
      treatment needs. AIMS: To describe and compare individual oral health care
      practices between MIH-affected and non-affected children, to evaluate and compare
      dental treatment needs between hypomineralised and non-hypomineralised first
      permanent molars, and to explore the role of reported fluoride exposure in the
      development of MIH. STUDY DESIGN: A cluster sample of 7-9 year-old Iraqi
      schoolchildren (823 of 1000 eligible, response rate 82.3%) had their first
      permanent molars and incisors evaluated using the European Academy of Paediatric
      Dentistry evaluation criteria for MIH. Of these 153 were diagnosed with the
      defect and were referred to as MIH-affected children. METHODS: Mothers of the
      participating children were asked to complete an oral health-questionnaire
      administered at schools. This included questions regarding child's history of
      dental visits, fluoride intake and the pattern of oral hygiene practices.
      Assessment of the dental treatment requirements for the first permanent molars
      was performed in a sample subset drawn from a larger data set of affected
      children (n=100) having their teeth assessed previously for dental caries status
      following the International Caries Detection and Assessment System. The sample
      subset consisted of 130 hypomineralised molars and 270 non-hypomineralised
      molars. RESULTS: Of the total sample, approximately 71% of parents had taken
      their children to the dentist at some stage. For the total sample, tooth
      restoration or extraction was the most likely causes for seeking dental care at
      the first dental appointment (57.9%). Tap water was the main source of water
      consumed at home by the majority of children (77.8%). The prevalence of dental
      caries and tooth restorations was higher in hypomineralised affected molars
      (78.5%) than in the defect-free molars (33.7%). STATISTICS: MIH-affected children
      reported significantly higher frequency of seeking dental care than their non
      affected counterparts (82.4%, 68.2%; respectively). They were over three times
      (OR = 3.18) more likely to visit the dentist complaining of pain and were over
      six times (OR = 6.37) more likely to seek dental care due to tooth sensitivity
      than their non-affected peers. No significant differences were found between the
      study groups in terms of tooth brushing and toothpaste history with brushing
      frequency "once-a-day" was commonly reported in both groups (75.5%). Early
      exposure to fluoridated water appeared to have a protective effect for MIH
      (OR=0.38). Affected molars required more than twice the amount of restorative
      care than unaffected molars. CONCLUSIONS: MIH did not seem to have an impact on
      the personal daily oral hygiene practices; however, MIH patients were commonly
      seeking dental consultation and needed care more often to improve their oral
      health.

PMID- 22883356
TI  - Comparative evaluation of effects of chemo-mechanical and conventional caries
      removal on dentinal morphology and its bonding characteristics - an SEM study.
AB  - AIM: To compare the efficacy of three caries removal techniques namely:
      Papacarie((r)), calcium hydroxide and rotary instruments by SEM analyses of the
      micro-morphology of residual dentine and resin tags at resin-dentine interface.
      METHODS: 45 extracted human permanent molar teeth, with occlusal caries extending
      up to dentine, were divided into two groups (Group 1 and 2) and each group was
      subdivided into three subgroups: subgroup A included teeth treated with
      conventional rotary method, subgroup B and C included those treated with calcium
      hydroxide and Papacarie((r)) respectively. Group 1 samples were prepared for
      viewing the micro-morphology of residual dentine (2000x and 5000x) and Group 2
      samples were filled with composite resin and analysed for resin tag formation
      (1000x) under SEM. RESULTS: Papacarie((r)) showed minimal smear layer and open
      dentinal tubules. Calcium hydroxide and rotary instruments showed a typical smear
      layer and occluded dentinal tubules. Resin tags obtained with Papacarie((r)) were
      the longest and significantly superior to those obtained with rotary and calcium
      hydroxide. CONCLUSIONS: Papacarie((r)) exhibited better bonding characteristics
      of residual dentine than calcium hydroxide and rotary method of caries removal.
      Thus, Papacarie((r)) is a suitable alternative to conventional method of caries
      removal, especially in paediatric patients.

PMID- 22883357
TI  - Effect of thermo-mechanical loading on marginal quality and wear of primary molar
      crowns.
AB  - AIM: To evaluate the effect of thermo-mechanical loading (TML) on marginal
      quality and wear of different crown types for primary molars. METHODS: Eighty
      extracted human primary molars were used. After preparation, five groups received
      different crowns (n=16): preformed metal crowns (3M ESPE) and NuSmile crowns
      (Orthodontic Technologies Inc.) were inserted as preformed metal crowns; as semi
      preformed crowns Protemp crowns (3M ESPE) were luted; and as individually
      manufactured resin composite crowns Filtek Z250 (3M ESPE) and Heliomolar (Ivoclar
      Vivadent) were used. Specimens were subjected to 2,500 thermal cycles between 5
      55(o)C and chewing simulation for 100,000 cycles at 50N at a frequency of 0.5 Hz.
      Before and after thermo-mechanical loading, impressions of the teeth were taken
      and replicas were made. The replicas received marginal quality evaluation under a
      SEM at x200 magnification. Occlusal wear was measured as vertical height loss
      using a 3-D laser scanning microscope. RESULTS: After TML, all crowns were
      intact. The adhesively bonded crowns showed significantly better marginal quality
      to dentine/cementum compared with GIC luted crowns (p<0.05). Laboratory made
      crowns showed a good fit and nearly transition-free margins also after TML.
      Preformed metal crowns showed the significantly lowest wear rates compared to the
      resin composites (p<0.05). Among the resin composite groups, Protemp exhibited
      the most pronounced wear depths (p<0.05). CONCLUSIONS: The different crown types
      under investigation showed a good performance concerning the evaluated parameters
      marginal quality and wear.

PMID- 22883358
TI  - Service evaluation of patients with orofacial granulomatosis and patients with
      oral Crohn's disease attending a paediatric oral medicine clinic.
AB  - AIM: Presenting features associated with orofacial granulomatosis (OFG) and oral
      Crohn's disease (OCD) are varied, making successful diagnosis and management
      difficult. The aim of this service evaluation was to establish a profile of
      patients with these conditions attending a paediatric oral medicine clinic and to
      determine their overall satisfaction with the care received. STUDY DESIGN: A
      retrospective case note analysis to establish the patient profile and a postal
      patient satisfaction questionnaire for service evaluation. METHODS: All patients
      with OFG and OCD who had attended the joint paediatric dentistry/oral medicine
      clinic at Charles Clifford Dental Hospital, Sheffield in the previous 14 years
      were included in the study. Hospital case notes were retrospectively reviewed and
      patient demographics, clinical features, investigations, diagnosis, treatment and
      outcomes of treatment were recorded. An anonymous patient satisfaction
      questionnaire using the Healthcare Satisfaction Generic Module of the Paediatric
      Quality of Life Inventory (PedsQLTM) was distributed to all patients by mail.
      RESULTS: A total of 24 patients (13 females and 11 males) were identified. Median
      age at presentation was 11 years (SD+/- 3.79, range 2-15). Fifteen patients (63%)
      were diagnosed with OCD, and 9 (37%) with OFG. Overall, the most common orofacial
      feature was oral ulceration (75%) followed by lip/facial swelling (71%), angular
      cheilitis (67%) and mucosal cobblestoning (67%). Differences in presentation were
      seen between the two conditions with oral ulceration (87%) and mucosal
      cobblestoning (80%) being the most frequently observed features of OCD and lip
      swelling (78%) and angular cheilitis (67%) being the most common features of OFG.
      58% of patients reported relief of symptoms through treatment. Thirteen patient
      satisfaction questionnaires were completed (54%). 85% (n=11) felt the overall
      care received in the clinic was 'excellent'. CONCLUSIONS: This service evaluation
      highlights the variety of presenting features of OFG and OCD. Despite only a
      moderate response to treatment, patient satisfaction with the service was high,
      emphasising the importance of good communication when managing children with
      chronic, debilitating conditions.

PMID- 22883359
TI  - Effects of folk medicinal plant extract Ankaferd Blood Stopper((r)) in vital
      primary molar pulpotomy.
AB  - AIM: To compare the clinical and radiographic success rates of two vital
      pulpotomy agents: formocresol (FC) and Ankaferd Blood Stopper((r)) (ABS), in
      primary molars during a 12-month follow-up period. STUDY DESIGN: A randomised,
      single-blind study design was used in a sample of 30 healthy 6-9 year old
      children with 60 carious primary molars without clinical or radiographic evidence
      of pulp degeneration. METHODS: The pulpotomy agents were assigned as follows:
      Group 1 was 1:5 diluted Buckley's formocresol (FC) and Group 2 was ABS. Clinical
      and radiographic follow-up at 3, 6, and 12 months used the following criteria:
      pain, swelling, sinus tract, mobility, internal root resorption, and furcation
      and/or periapical bone destruction. STATISTICS: The data were analysed using Chi
      square tests. RESULTS: The clinical and radiographic evaluation at 3 months
      revealed total success rates of 100% in the FC and ABS groups. Success rates in
      FC and ABS groups at 6 months were 96.7% and 93.3% respectively. At the 12-month
      follow-ups, the total success rates in the FC, and ABS groups were 89.3% and
      85.7%, respectively. When the groups were compared according to the time
      intervals, no significant differences were observed between the 3, 6, and 12
      month values. The success rates of the materials decreased over time.
      CONCLUSIONS: FC and ABS were found successful as pulp dressings in primary
      molars. ABS appears to be an alternative pulpotomy agent but periodical follow
      ups must be considered to evaluate long term success rates.

PMID- 22883360
TI  - Early prognostic indicators and outcome prediction model for replanted avulsed
      teeth.
AB  - AIM: To identify early clinical variables that are most predictive of treatment
      outcome and to develop a model that will allow prediction of treatment outcomes
      based on these variables. STUDY DESIGN AND METHODS: A dental trauma database was
      used to randomly identify patients who had received treatment for avulsed teeth
      between 1998 and 2007. A data extraction form was designed and completed for each
      tooth. Demographic, diagnostic and treatment information recorded in the
      patient's records, in addition to radiographs, were viewed retrospectively.
      STATISTICS: The significance and the predictive power for each early clinical
      variable were assessed using a univariate logistic regression model. Only
      significant variables (p<0.05) were considered eligible for the prediction model
      and a c-index was then constructed for their respective predictive power (0.5 =
      no predictive power, 1.0 = perfect prediction). RESULTS: Of the original sample
      of 213 patients who had received treatment for avulsed teeth between 1998-2007
      only 105 fulfilled the criteria for evaluation. Two models ('At first visit' and
      'at initial treatment visits') were produced with a total of five variables that
      were significant and holding the greatest predictive power (high c-index):
      patient age (p=0.001, c=0.80); stage of root formation (p=0.001, c=0.76); storage
      medium (p=0.047, c=0.58); tooth mobility after dressing (p=0.001, c=0.70); and
      tooth mobility after splinting (p=0.003, c=0.70). These variables underwent multi
      variate analysis and the final models had good predictive abilities (c-index of
      0.80 and 0.74). CONCLUSION: These predictive models based on patient age, stage
      of root formation, storage medium, tooth mobility after dressing and tooth
      mobility after splinting were shown to have high predictive value and will enable
      a clinician to estimate the long term prognosis of avulsed and replanted teeth.
      It will enable planning for further treatment with a realistic view of outcome at
      an early stage.

PMID- 22883361
TI  - Indications for the use of auto-transplantation of teeth in the child and
      adolescent.
AB  - BACKGROUND: Tooth auto-transplantation has been successfully performed for over
      50 years and yet the procedure has still to receive the widespread acceptance
      that it deserves. AIM: This study demonstrates the numerous clinical situations
      in which auto-transplantation can be used in order to give a child or adolescent
      an excellent biological long-term replacement. INDICATIONS: Seven cases are
      presented that demonstrated the versatility of auto-transplantation in a range of
      clinical situations. The aim was to show that this technique is not only useful
      for replacing teeth that are lost due to trauma but has applications for the
      replacement of teeth that are developmentally missing, or teeth with otherwise
      poor long-term prognosis. TREATMENT: All cases presented were managed with
      autotransplatation and included patients with hypodontia, trauma, dilacerated
      incisors, ankylosis, failed endodontic treatment and aesthetic management of a
      patient with cleft lip and palate. FOLLOW-UP: Medium and long-term outcomes were
      demonstrated. CONCLUSIONS: Auto-transplantation provides an excellent outcome in
      a growing child with the advantage that it is a biologically compatible method of
      tooth replacement, which promotes pulp and periodontal healing and enables
      orthodontic movement if necessary.

PMID- 22883362
TI  - Case report: management of crown-root fracture in lower first primary molar
      caused by injury to the chin: report of an unusual case.
AB  - BACKGROUND: Dental traumas are highly prevalent lesions in primary teeth, but
      crown-root fractures are seldom observed in primary molars. When trauma is
      sustained to the chin, the posterior primary teeth are at increased risk of
      trauma. The treatment of fractured teeth can be complicated, sometimes because of
      difficulties with the final restoration. CASE REPORT: A 4-year-old girl was
      referred to a Specialty Dental clinic by a general dental practitioner with
      complaints of pain in her left mandibular posterior teeth region while biting.
      History revealed that she had fallen ten days before while playing. Chin
      laceration was sutured in the trauma centre, but no dental treatment was carried
      out. She was subsequently discharged. Later, she had pain while biting for which
      she was referred to the clinic by her general dental practitioner. Extra-oral
      examination demonstrated a healing laceration on the chin. Radiographic
      examination showed the presence of an unusual complicated crown-root fracture of
      the left mandibular first primary molar. Pulpectomy was carried out and the
      fracture was stabilised with glass ionomer cement and a preformed metal crown was
      placed. FOLLOW-UP: Patient was reviewed after 3, 6 and 12 months both
      radiographically and clinically. Though radiographically it was found that the
      obturating material was resorbed completely at the 12 month visit, clinically the
      patient was asymptomatic until now (after 15 months). The patient is still under
      review. CONCLUSION: This case highlights the need for a systematic history and
      examination in all cases of dental trauma. It also demonstrates that conservative
      management is possible and not all primary teeth with crown-root fractures need
      to be extracted.

PMID- 22883363
TI  - Case report: pre-eruptive intra-coronal radiolucencies revisited.
AB  - AIM: Pre-eruptive intra-coronal radiolucency (PEIR) describes a radiolucent
      lesion located in the coronal dentine, just beneath the enamel-dentine junction
      of unerupted teeth. The prevalence of this lesion varies depending on the type
      and quality of radiographic exposure and age of patients used for assessment. The
      aetiology of pre-eruptive intra-coronal radiolucent lesions is not fully
      understood, but published clinical and histological evidence suggest that these
      lesions are resorptive in nature. Issues around the diagnosis, treatment planning
      and clinical management of this lesion are explored using previously unreported
      cases. CASE REPORTS: Case 1: A ten-year-old girl attended for a routine check-up.
      An intra-coronal radiolucency in the unerupted lower right second premolar was an
      incidental finding on orthopantomograph (OPT). The tooth erupted and removal of
      enamel revealed a space filled with soft red tissue, unlike carious dentine in
      appearance. The tooth was restored with an indirect pulp cap, resin modified
      glass ionomer base and composite resin. Tissue from the lesion was removed for
      histopathological investigation. Root development continued to completion and the
      tooth remained asymptomatic and vital. Case 2: A six-year-old girl attended for
      her first dental visit. An intra-coronal radiolucency in a lower right first
      permanent molar was noted on baseline bitewing radiographs. The lesion was
      monitored and fissured sealed upon eruption. The lesion was monitored annually
      radiographically. The tooth remained symptom free for 5 years. The patient
      presented on an emergency basis having fractured the distolingual cusp overlying
      the lesion. There was no pain and the tooth was vital. The softened dentine was
      removed and the tooth was restored using a preformed metal crown. Case 3: A 12
      year-old girl was referred for restoration of mandibular left second permanent
      molar. Clinically there was extensive occlusal destruction. Review of a previous
      OPT showed that an intra-coronal radiolucency was present in tooth 37 at least
      one year prior to its eruption. The large mass of coronal soft tissue was
      removed, the remaining enamel shell was deemed to be unrestoreable and the tooth
      was extracted. The patient was referred back to an orthodontist for completion of
      orthodontic treatment. CONCLUSION: Early detection and classification of the PEIR
      lesion allows an array of individualised treatments to be provided for successful
      outcome.

PMID- 22883364
TI  - Home dampness, beta-2 adrenergic receptor genetic polymorphisms, and asthma
      phenotypes in children.
AB  - BACKGROUND: Dampness in the home is a strong risk factor for respiratory symptoms
      and constitutes a significant public health issue in subtropical areas. However,
      little is known about the effects of dampness and genetic polymorphisms on
      asthma. METHODS: In 2007, 6078 schoolchildren were evaluated using a standard
      questionnaire with regard to information about respiratory symptoms and
      environmental exposure. Multiple logistic regression analyses were performed to
      assess the effects of home dampness and beta-2-adrenergic receptor (ADRB2) gene
      polymorphisms on the prevalence of asthma and selected indicators of severity of
      asthma. RESULTS: The frequency of mildewy odor, the number of walls with water
      stamp, and the duration of water damage were all associated with being awakened
      at night due to wheezing. However, no other clear-cut associations were found for
      any of the other indicators of asthma. Children exposed to mildewy odor with
      ADRB2 Arg/Arg genotype were associated with being awakened at night due to
      wheezing (OR=1.95, 95% CI, 1.14-3.36), compared to those without exposure and
      with the ADRB2 Gly allele. ADRB2 Arg16Gly showed a significant interactive effect
      with home dampness on being awakened at night due to wheezing and current
      wheezing, but no significant effect on active asthma and medication use.
      Frequency and degree of home dampness were also associated with the prevalence of
      asthma and selected indicators of severity of asthma, in an exposure-response
      manner among children with ADRB2 Arg/Arg genotype. CONCLUSIONS: Home dampness
      prevention is one of the important steps of asthma control, especially in
      children carrying ADRB2 Arg/Arg genotypes.

PMID- 22883365
TI  - [Meningococcal vaccine. Editorial].

PMID- 22883366
TI  - [Paediatric meningococcal meningitis in France: ACTIV/GPIP network results].
AB  - BACKGROUND: The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pediatrique and
      Association Clinique et Therapeutique Infantile du Val de Marne) set up an active
      surveillance network to analyze the epidemiological, clinical and biological
      features of meningococcal meningitis. METHODS: French pediatric wards working
      with 166 microbiology laboratories enrolled all children (0-18 years old) with
      bacterial meningitis. Risk factors, signs and symptoms, vaccination status,
      cerebrospinal fluid analysis, treatments and case fatality rate were recorded.
      RESULTS: Since 2001, 1661 meningococcal meningitis were reported among 3769
      (44.1%) bacterial meningitis. Mean age was 4.4- year- old (+/- 4.8, median 2.5)
      and 2/3 cases occurred in children under 5- year- old (68.8%). Serogroup B
      (61.3%) is preponderant following by serogroup C (27.0%). 27.5% of children had
      received an antibiotic treatment 24 hours before lumbar puncture. A shock is
      reported in 31.0% of cases. No cases of meningococcal meningitis C has been
      reported in children vaccinated with a conjugate vaccine. Two children vaccinated
      with MenBvac((r)) vaccine had a meningitis B14:P1.7,16. Global case fatality rate
      was 6.5% but was higher (9.2%) for serogroup C than for serogroup B (5.9%)
      (p=0.02). CONCLUSION: This is among the largest series of microbiologically
      documented meningococcal meningitis to date (1661 cases). In France,
      meningococcal is responsible for approximately 50 % of meningitis. Effective
      meningococcal serogroup B vaccine and serogroup C vaccination recommendation
      could control the burden of meningococcal meningitis.

PMID- 22883367
TI  - [Neisseria meningitidis: characterisation and epidemiology].
AB  - Neisseria meningitidis are Gram-negative cocci, whose reservoir is exclusively
      human. This bacterium has several virulence factors including capsule with
      antiphagocytic properties, lipopolysaccharide, iron uptake system, pili and an
      IgA1 protease. The strains can be typed by immunological or genotypic methods.
      Phenotypic determination defines the serogroup, serotype, subtype and immunotype.
      Molecular typing, a very discriminating method, allows the determination of
      clonal complexes. These two epidemiological approaches allow the characterization
      of N. meningitidis strains. Conversely to the other strains, invasive strains
      belong to a very limited number of clonal complexes (CC). The evolution of the
      genome of N. meningitidis is the consequence of horizontal transfer of DNA
      occurring by transformation or recombination and leading to capsular exchanges.
      The distribution of the different serogroups varies according to the different
      countries. In France, in 2010, the serogroups B, C, W135 and Y accounted
      respectively for 72%, 17%, 5% and 2% of cases of invasive infections. The recent
      emergence of serogroup X in Niger highlights the need for continuing
      epidemiological surveillance.

PMID- 22883368
TI  - [Meningococcal vaccines: from polysaccharide to conjugate vaccines].
AB  - Vaccines against the polysaccharide meningococcal capsule lead to the prevention
      of invasive meningococcal diseases due to serotypes A, C, Y, W135. Polysaccharide
      vaccines, according to their immunological characteristics, could be used only to
      protect during a risk period relatively short: travel in endemic areas, epidemics
      and index cases. The dramatic success of the implementation of meningococcal C
      conjugate vaccines in England, and in several European countries has opened new
      perspectives. Three ACYW135 conjugate vaccines are or will soon be available.
      Meningococcal conjugate vaccines may be used for the same indications than
      polysaccharides vaccines, but also for long term individual protection (both for
      patient at high risk or without risk factor) and in national immunization
      programs. They must replace polysaccharide vaccines notably because of the risk
      of immunologic hypo-responsiveness.

PMID- 22883369
TI  - [Meningococcal serogroup B vaccines].
AB  - The diversity and antigenic variability of Neisseria meningitidis serogroup B
      strains around the world has been a major challenge to developing a vaccine with
      broad coverage. Outer-membrane vesicle vaccines appear to be safe and effective
      but are strain-specific vaccines and used in delimited areas. Also, recombinant
      protein vaccines such as factor H binding protein, given alone or in combination
      with others antigens have been developed and may be effective against the
      majority of group B strains.

PMID- 22883370
TI  - [Anti-meningococcal vaccines: diversity of vaccination policies and
      recommendations].
AB  - In European Country, Canada, Australia and Brazil immunization program with
      conjugate meningococcal C, including universal vaccination of infants or
      toddlers, with a catch-up program up to 19 y in several areas, have been
      successful in reducing disease incidence through direct and indirect protection.
      In USA, quadrivalent conjugate vaccines targeting serogroups ACYW135 are used in
      programs of adolescent immunization at 10 and 15 years because serotype Y is
      frequent. A mass immunization campaign against serogroupe A disease with a
      conjugate vaccine is beginning in African belt of meningitis. Polysaccharide
      vaccines A, C or ACYW135 are used in travelers but quadrivalent conjugate
      vaccine, with larger targets, gives higher titers after booster and must be
      preferred. Some questions are pending: immunize before or after one year of age,
      a booster dose in adolescence and the routine use of quadrivalent conjugate
      vaccine in Europe if the incidence of serotype Y is growing.

PMID- 22883371
TI  - A dating success story: genomes and fossils converge on placental mammal origins.
AB  - The timing of the placental mammal radiation has been a source of contention for
      decades. The fossil record of mammals extends over 200 million years, but no
      confirmed placental mammal fossils are known prior to 64 million years ago, which
      is approximately 1.5 million years after the Cretaceous-Paleogene (K-Pg) mass
      extinction that saw the end of non-avian dinosaurs. Thus, it came as a great
      surprise when the first published molecular clock studies suggested that
      placental mammals originated instead far back in the Cretaceous, in some cases
      doubling divergence estimates based on fossils. In the last few decades, more
      than a hundred new genera of Mesozoic mammals have been discovered, and molecular
      divergence studies have grown from simple clock-like models applied to a few
      genes to sophisticated analyses of entire genomes. Yet, molecular and fossil
      based divergence estimates for placental mammal origins have remained remote,
      with knock-on effects for macro-scale reconstructions of mammal evolution. A few
      recent molecular studies have begun to converge with fossil-based estimates, and
      a new phylogenomic study in particular shows that the palaeontological record was
      mostly correct; most placental mammal orders diversified after the K-Pg mass
      extinction. While a small gap still remains for Late Cretaceous supraordinal
      divergences, this study has significantly improved the congruence between
      molecular and palaeontological data and heralds a broader integration of these
      fields of evolutionary science.

PMID- 22883372
TI  - Mortality after low trauma hip fracture: a prospective cohort study.
AB  - BACKGROUND: Various risk of mortality due to hip fracture has been reported by
      different studies. There is scarce controlled study on hip fracture mortality
      from developing countries and no data from Middle East region. The objective of
      this study is to determine mortality and its risk factors one year after low
      trauma hip fracture. METHODS: One hundred and two patients after hip fracture not
      caused by high impact injuries or local bone diseases followed up prospectively
      for one year. Control group consisted of sex and age matched patients admitted to
      ophthalmology ward for eye surgery. Data about comorbidity obtained from both
      groups at baseline. Functional state and health-related quality of life for the
      participants were measured using RDRS-2 and SF-36 questionnaires, respectively.
      RESULTS: The overall survival was 83% in cases and 92% in controls (log rank test
      3.62, df = 1, P = 0.057). Early mortality within the first 6 months of
      observation was significantly higher in patients than controls (13 in patients
      vs. 2 in controls) (log rank test 8.84, df = 1, P = 0.003). The risk of mortality
      in the first year after fracture was significantly and independently associated
      with age and baseline RDRS score. By the end of follow-up, in the patient group,
      55.4% of survivors were able to walk without any assistance and 10.8% were not
      able to walk. CONCLUSIONS: The risk of mortality within the first 6 months of
      observation was significantly and independently associated with low trauma hip
      fracture. However, age and baseline RDRS score were independent predictors of
      mortality in the first year following hip fracture.

PMID- 22883373
TI  - The management of menopausal symptoms in breast cancer survivors: case-based
      approach.
AB  - INTRODUCTION: The intensified treatment of breast cancer improves survival but
      has a price in terms of side-effects. The main side-effects, such as vasomotor
      symptoms and impaired sexual functioning, are related to premature menopause due
      to chemotherapy and/or anti-hormonal therapy. Though for some women these
      symptoms are bearable, for others they have a large impact on their quality of
      life. The paper discusses the menopausal symptoms most frequently reported by
      breast cancer survivors and current treatment options. METHODS: A literature
      review is presented of menopausal symptoms after breast cancer and management
      strategies, illustrated by two cases. SUMMARY: Vasomotor symptoms can be relieved
      by lifestyle adaptation, acupuncture and non-hormonal agents such as venlafaxine,
      gabapentin or clonidine. Impaired sexual functioning can be treated by couple
      based sexual counselling or psycho-educational therapy. Painful intercourse due
      to vaginal dryness can be alleviated by vaginal lubricants and moisturizers, but
      is most effectively treated by vaginal estriol. Local estriol seems safe if used
      for a short period (less than six weeks). Because of proven increased risk of
      recurrence with hormone replacement therapy (HRT), it should not be prescribed
      for breast cancer survivors, although exceptions could be made of selected cases
      of fully informed BRCA mutation carriers after ER-negative breast cancer and with
      severe menopausal symptoms due to prophylactic oophorectomy at a young age and
      (preferably) after mastectomy. CONCLUSION: The management of vasomotor symptoms
      and impaired sexual functioning in breast cancer survivors should focus on
      lifestyle and, if necessary, non-hormonal pharmacological interventions.

PMID- 22883374
TI  - The role of exercise capacity in the health and longevity of centenarians.
AB  - Ageing is a continuum of biological processes characterized by progressive
      adaptations which can be influenced by both genetic and physiological factors. In
      terms of human maturation, physically and cognitively functional centenarians
      certainly represent an impressive example of successful healthy ageing. However,
      even in these unique individuals, with the passage of time, declining lung
      function and sarcopenia lead to a progressive fall in maximal strength, maximal
      oxygen uptake, and therefore reduced exercise capacity. The subsequent mobility
      limitation can initiate a viscous downward spiral of reduced physical function
      and health. Emerging literature has shed some light on this multi-factorial
      decline in function associated with aging and the positive role that exercise and
      physical capacity can play in the elderly. Recognizing the multiple factors that
      influence ageing, the aim of this review is to highlight the recently elucidated
      limitations to physical function of the extremely old and therefore evaluate the
      role of exercise capacity in the health and longevity of centenarians.

PMID- 22883376
TI  - [The textual research on the evolution of the toothbrush shape in ancient China].
AB  - Archaeological discovery demonstrates that the ancient plant hair brush first
      appeared in the Tang dynasty. According to the evolution of the shape of the head
      and handle of the toothbrush in ancient times, we can divide the evolution of the
      shapes into three major stages of development: (1) the Tang and the Five
      dynasties; (2) the Liao, Song, Jin, Yuan dynasties; (3) Ming, Qing and the
      Republic periods. The toothbrush heads and handles had no significant differences
      during the Tang and the Five dynasties. However, the shapes of them in the Liao,
      Song, Jin, Yuan dynasties are somewhat different. In the Ming and Qing and the
      republic of China periods, the shape of toothbrush head and handle had further
      refinement. Recently, some scholars raised doubts about the "plant hair
      toothbrush doctrine". They believe that the archaeological bone graft handle
      brush was used to wipe hair oil or clean water when washing and dressing.
      However, according to shape and function and ancient literature records, the
      archaeological bone graft handle brush should be a plant hair toothbrush used to
      clean and protect teeth.

PMID- 22883375
TI  - Dietary supplements for benign prostatic hyperplasia: an overview of systematic
      reviews.
AB  - Benign prostatic hyperplasia (BPH) is a common chronic condition in older men.
      The aim of this overview of systematic reviews (SRs) is to summarise the current
      evidence on the efficacy and adverse effects of dietary supplements for treating
      BPH with lower urinary tract symptoms. We searched 5 electronic databases and
      relevant overviews without limitations on language or publication status. Six SRs
      of 195 articles were included in this overview. Serenoa repens was reviewed in 3
      studies and no specific effect on BPH symptoms and urinary flow measures was
      observed. However, beta-sitosterol, Pygeum africannum and Cernilton were reviewed
      in one study each, and significant improvement was observed for all three. All
      the included compounds have mild and infrequent adverse effects. SRs on beta
      sitosterol, Pygeum africannum and Cernilton have not been updated since 2000,
      thus an update of reviews on these compounds will be necessary in the future.

PMID- 22883377
TI  - [Treatment for dystocia in ancient China].
AB  - Treatment for dystocia in ancient China includes delivery taboo, delivery
      promotion decoction and midwifery methods. Before the Sui and Tang dynasties,
      delivery was more like a rite. In the Sui and Tang dynasties, doctors began to
      understand dystocia from the physical condition, delivery environment and
      psychological factors, and the delivery taboo was rejected. After that period,
      the delivery taboo became a folk custom and was separated from the field of
      medicine. The herbs for delivery promotion decoctions usually used the principle
      of regulating the blood and removing stasis and were of slippery character during
      and before the Tang dynasty. In the Song dynasty promotion decoction was
      enlarged. In later ages some doctors put forward that emphasis should be on
      conformity to nature and nursing, not dependence on promotion drugs. Before and
      during the Tang dynasty, acupuncture and salt smearing had been key methods for
      abnormal fetal position and there were also case recordings. In the Northern Song
      dynasty, these two methods were no longer used and the midwife's skill was
      emphasized. With more and more focus on the midwife's skill, some male doctors
      depended on midwives and some criticism of midwives also increased. The book
      Dashengbian reflected maximum distrust of midwives.

PMID- 22883378
TI  - [Analysis of the time recorded in Canggongzhuan].
AB  - Shiji.Bianquecanggong Liezhuan is the first biography in official history. The
      doctor of the Western Han dynasty-Chunyu Yi, recorded in Canggongzhuan, was an
      actual historical figure. Recordings about his time of life, social background
      and medical stories were full and accurate. But the time of events recorded in
      that book was inaccurate. After analysis of related material, it transpired that
      Chun Yuyi was put into jail in the 13(th) year of the Emperor Hanwen Period, not
      the 4(th) year, and he answered the questions of the Emperor Hanwen in the 13(rd)
      ~ 14(th) year when he was 39 ~ 40 years old.

PMID- 22883379
TI  - [Study of MA Shi and ZHANG Jiebin's Annotations of Nei Jing].
AB  - MA Shi and ZHANG Jie-bin are famous annotators of Huangdi Neijing and their
      annotations are well- regarded. However, influenced by the style of practice of
      the Ming dynasty, some of their annotations are less than satisfactory. For
      instance, the words "ni" and "cong" in the phrase "Ni cong yin yang" are
      synonyms, which mean obedience, and the meaning of the word "an" in the phrase
      "an er shou zhi" is not "message" or "examination" but "inhibition". Also, the
      word "zou" in the phrase "gu hao zou" is "to run"; "qu" in the phrase "qu pijie"
      means "to leave". This thesis raises several incorrect annotations for the
      readers' reference.

PMID- 22883380
TI  - [The textual research on the original plant of grass monkshood].
AB  - According to the literature review and field investigation, the traditional
      production areas of the herb grass monkshood are East China, Sichuan and its
      surroundings. The protophytes of grass monkshood in the east China area are
      mainly the Huangshan monkshood variant and truppelianum; but in the Sichuan area
      they are mainly aconite and aconitum hemsleyanum. The above belong to the
      aconitum of aconitum suby and tendril monkshood. They are the closest genetic
      relatives and the most evolutive groups as well as the most toxic groups. Local
      aconite was used as grass monkshood medicine in folk medicine but this happened
      only in part of the region and for a period of time. There were few records in
      literature in past dynasties and they would not have been able to be included in
      mainstream history. It is obviously different from the aconitum kusnezoffii which
      is stipulated in the pharmacopoeia in past ages. It is not in accordance with
      history to take kusnezoffii as certified quality grass monkshood and it also has
      some particular influence on the clinical use of grass monkshood.

PMID- 22883381
TI  - [Birthplace of the Qi-Huang culture-Xinmi of the Henan Province].
AB  - Located in the central plains and the eastern slope of songhsan, Xinmi has a long
      history and unique advantage in environment. As the birthplace of Qi-Huang
      culture, it has abundant Qibo and Huangdi relics (Xuanyuan tpe, Qibo tomb, Qibo
      temple, Qibo spring, Huangdi palace and Qibo mountain), folk tales about their
      academic discussion which were popular long time ago, many archaeological
      discoveries with academic value and genuine Chinese medicinal materials. Qi-Huang
      culture is the valuable Chinese culture heritage and it needs to be further
      studied and developed.

PMID- 22883382
TI  - [The characteristics and influence of the health culture of tibetan medicine].
AB  - The Tibetan people's knowledge on preserving health is an important part of
      Tibetan medical culture. Most of the Tibetans live on the plateau where it is
      cold with decreased oxygen. They are devout Buddhists and they have developed a
      variety of healthy folk customs. These factors form the health culture of Tibetan
      medicine and demonstrate the plateau characteristics of health, psychology health
      and health customs. The health culture of Tibetan medicine has far-reaching
      influence because of the spread of Buddhism. Therefore it is worth exploring and
      carrying forward.

PMID- 22883383
TI  - [The review of the composition of Za Liao Fang of Jinguiyaolue (Synopsis of
      Prescriptions of the Golden Chamber)].
AB  - The contents of Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber)
      can mainly be divided into 2 parts, which are "text" and "attached formulas". It
      is mostly thought that the "text" has more content than the "attached formulas".
      After comparing the small character version of WU Qian's transcript, which was
      recently published,with the large character version of Jinguiyaolue, and doing
      textual research on the "attached formulas" in Za Liao Fang of Jinguiyaolue
      (Synopsis of Prescriptions of the Golden Chamber) according to the clues left by
      the Bureau of the Revision of Medical Books in Song Dynasty, we can find that
      there are only "chai hu decoction with addition or subtraction in four seasons"
      and "the Kele pear pill for taking for long periods" which belong to the Song
      masters' copy. However, another 22 prescriptions called "attached formulas" were
      added when the Song masters revised it.

PMID- 22883384
TI  - Monitor units are not predictive of neutron dose for high-energy IMRT.
AB  - BACKGROUND: Due to the substantial increase in beam-on time of high energy
      intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target
      dose compared to conventional treatment techniques, an increased dose of scatter
      radiation, including neutrons, is delivered to the patient. As a consequence, an
      increase in second malignancies may be expected in the future with the
      application of intensity-modulated radiotherapy. It is commonly assumed that the
      neutron dose equivalent scales with the number of monitor units. METHODS:
      Measurements of neutron dose equivalent were performed for an open and an
      intensity-modulated field at four positions: inside and outside of the treatment
      field at 0.2 cm and 15 cm depth, respectively. RESULTS: It was shown that the
      neutron dose equivalent, which a patient receives during an intensity-modulated
      radiotherapy treatment, does not scale with the ratio of applied monitor units
      relative to an open field irradiation. Outside the treatment volume at larger
      depth 35% less neutron dose equivalent is delivered than expected. CONCLUSIONS:
      The predicted increase of second cancer induction rates from intensity-modulated
      treatment techniques can be overestimated when the neutron dose is simply scaled
      with monitor units.

PMID- 22883385
TI  - External magnetic field-induced selective biodistribution of magnetoliposomes in
      mice.
AB  - This study looked at the effect of an external magnet on the biodistribution of
      magnetoliposomes intravenously administrated in mice (8 mg iron/kg) with and
      without induced acute inflammation. Our results showed that due to enhanced
      vascular permeability, magnetoliposomes accumulated at the site of inflammation
      in the absence of an external magnetic field, but the amount of iron present
      increased under the effect of a magnet located at the inflammation zone. This
      increase was dependent on the time (20 or 60 min) of exposure of the external
      magnetic field. It was also observed that the presence of the magnet was
      associated with lower amounts of iron in the liver, spleen, and plasma than was
      found in mice in which a magnet had not been applied. The results of this study
      confirm that it is possible to target drugs encapsulated in magnetic particles by
      means of an external magnet.

PMID- 22883386
TI  - Painting by numbers: a guide for systematically developing indicators of
      performance at any level of health care.
AB  - OBJECTIVES: There is a need for methods to facilitate selection of robust
      indicators in health care settings. This research aims to determine the key steps
      in, and delineate a systematic process for, construction of health care
      performance indicators. METHODS: Information derived from a review of the
      published literature and analysis of key informant interviews was synthesised to
      derive key activities and concepts fundamental to, and essential for, the
      development of robust and meaningful indicators. These activities and concepts
      were ordered into a logical sequence. RESULTS: A sequence of six stages
      (prioritisation; intent; implementation requirements; measure specifications;
      indicator assessment; target development), with a series of steps within each
      stage, was delineated. This sequence comprises the Systematic Indicator
      Development (SID) Method, which may be utilised by health care policy decision
      makers, providers, or clinicians in a 'paint by numbers' manner to create robust
      and meaningful indicators, or to refine or amend existing indicators.
      CONCLUSIONS: The SID Method blends different aspects of indicator art and science
      and structures it in a logical way to provide transparency, consistency and
      rigour to indicator construction. The approach ensures that all health care
      sector stakeholders can make informed decisions when selecting indictors or
      interpreting obtained results.

PMID- 22883387
TI  - Trends and levels of avoidable mortality among districts: "healthy" benchmarking
      in Germany.
AB  - All developed nations use indicators to monitor the health of their populations,
      but few nations provide a systematic monitoring of indicators for small regional
      units. The present study aims to contribute to the literature a single graph that
      provides a quick and comprehensive overview of the level of and trend in
      avoidable mortality in each German district as compared to the national average
      and development. Using mortality data from the German Federal Statistical Office,
      I calculated the age-standardized number of avoidable deaths, separately for men
      and women, in each of the 413 local districts in Germany between 2000 and 2008.
      For men, the graph illustrates that the districts with the highest rates of
      avoidable mortality are still located in the former East German states, but that
      some of these districts have improved significantly between the years 2000 and
      2008 and are approaching the nationwide average. The graph for women shows
      slightly different results. Here, many urban areas show high rates of avoidable
      mortality with both favorable and unfavorable trends. Health professionals could
      use the graph to establish realistic benchmarks that are based on countrywide
      comparisons of districts to a national average and trend, which may in turn help
      them to identify local districts in need of primary or secondary prevention
      programs or a more effective provision of health care.

PMID- 22883389
TI  - Kidney disease.

PMID- 22883388
TI  - Polymorphisms in the genes coding for iron binding and transporting proteins are
      associated with disability, severity, and early progression in multiple
      sclerosis.
AB  - BACKGROUND: Iron involvement/imbalance is strongly suspected in multiple
      sclerosis (MS) etiopathogenesis, but its role is quite debated. Iron deposits
      encircle the veins in brain MS lesions, increasing local metal concentrations in
      brain parenchyma as documented by magnetic resonance imaging and histochemical
      studies. Conversely, systemic iron overload is not always observed. We explored
      the role of common single nucleotide polymorphisms (SNPs) in the main iron
      homeostasis genes in MS patients. METHODS: By the pyrosequencing technique, we
      investigated 414 MS cases [Relapsing-remitting (RR), n=273; Progressive, n=141,
      of which: Secondary (SP), n=103 and Primary (PP), n=38], and 414 matched healthy
      controls. Five SNPs in 4 genes were assessed: hemochromatosis (HFE: C282Y, H63D),
      ferroportin (FPN1: -8CG), hepcidin (HEPC: -582AG), and transferrin (TF: P570S).
      RESULTS: The FPN1-8GG genotype was overrepresented in the whole MS population
      (OR=4.38; 95%CI, 1.89-10.1; P<0.0001) and a similar risk was found among patients
      with progressive forms. Conversely, the HEPC -582GG genotype was overrepresented
      only in progressive forms (OR=2.53; 95%CI, 1.34-4.78; P=0.006) so that SP and PP
      versus RR yielded significant outputs (P=0.009). For almost all SNPs, MS
      disability score (EDSS), severity score (MSSS), as well as progression index (PI)
      showed a significant increase when comparing homozygotes versus individuals
      carrying other genotypes: HEPC -582GG (EDSS, 4.24+/-2.87 vs 2.78+/-2.1; P=0.003;
      MSSS, 5.6+/-3.06 vs 3.79+/-2.6; P=0.001); FPN1-8GG (PI, 1.11+/-2.01 vs 0.6+/
      1.31; P=0.01; MSSS, 5.08+/-2.98 vs 3.85+/-2.8; P=0.01); HFE 63DD (PI, 1.63+/-2.6
      vs 0.6+/-0.86; P=0.009). Finally, HEPC -582G-carriers had a significantly higher
      chance to switch into the progressive form (HR=3.55; 1.83-6.84; log-rank
      P=0.00006). CONCLUSIONS: Polymorphisms in the genes coding for iron binding and
      transporting proteins, in the presence of local iron overload, might be
      responsible for suboptimal iron handling. This might account for the significant
      variability peculiar to MS phenotypes, particularly affecting MS risk and
      progression paving the way for personalized pharmacogenetic applications in the
      clinical practice.

PMID- 22883390
TI  - Antidiabetic medications in patients with type 2 diabetes mellitus and severe
      renal impairment: an update.

PMID- 22883392
TI  - Spectral analysis of EMG using intramuscular electrodes reveals non-linear
      fatigability characteristics in persons with chronic low back pain.
AB  - Greater fatigability across lumbar extensors has been reported in persons with
      chronic low back pain (LBP), however, extensor atrophy tends to be local to the
      site of pain. Therefore, specific ultrasound guided local and remote
      intramuscular electromyographic recordings were undertaken during an isometric
      horizontal trunk hold in two carefully matched cohorts; persons with and without
      LBP. The test was performed to self-determined maximal hold time, and the control
      group held the horizontal position longer (P < 0.001). A power spectral analysis
      was performed to calculate the normalized median frequency (NMF) slope for both
      the first and last 30s of the fatigue test due to the group difference in hold
      times. There were no significant group differences in NMF slope at the first 30s
      of testing (P = 0.650). The NMF slope for the first and last 30s was not
      different in healthy subjects (P = 0.688), but was different in persons with LBP,
      illustrated by shallowing of the slope at the last 30s of the test (P = 0.008). A
      between muscle comparison in the LBP group showed greater non-linear behavior in
      the deep multifidus (painful region) in contrast to T10 longissimus thoracis
      (nonpainful region) (P = 0.013). Possible explanations for these findings are
      discussed.

PMID- 22883393
TI  - Comparative mode of action of novel hybrid peptide CS-1a and its rearranged
      amphipathic analogue CS-2a.
AB  - Cell selective, naturally occurring, host defence cationic peptides present a
      good template for the design of novel peptides with the aim of achieving a short
      length with improved antimicrobial potency and selectivity. A novel, short
      peptide CS-1a (14 residues) was derived using a sequence hybridization approach
      on sarcotoxin I (39 residues) and cecropin B (35 residues). The sequence of CS-1a
      was rearranged to enhance amphipathicity with the help of a Schiffer-Edmundson
      diagram to obtain CS-2a. Both peptides showed good antibacterial activity in the
      concentration range 4-16 MUg.mL(-1) against susceptible as well as drug-resistant
      bacterial strains, including the clinically relevant pathogens Acenatobacter sp.
      and methicillin-resistant Staphylococcus aureus. The major thrust of these
      peptides is their nonhaemolytic activity against human red blood cells up to a
      high concentration of 512 MUg.mL(-1). Compared to CS-1a, amphipathic peptide CS
      2a showed a more pronounced alpha-helical conformation, along with a better
      membrane insertion depth in bacterial mimic 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) small
      unilamellar vesicles. With equivalent lipid-binding affinity, the two peptides
      assumed different pathways of membrane disruption, as demonstrated by calcein
      leakage and the results of transmission electron microscopy on model bacterial
      mimic large unilamellar vesicles. Extending the work from model membranes to
      intact Escherichia coli cells, differences in membrane perturbation were visible
      in microscopic images of peptide-treated E. coli. The present study describes two
      novel short peptides with potent activity, cell selectivity and divergent modes
      of action that will aid in the future design of peptides with better therapeutic
      potential.

PMID- 22883394
TI  - Causation in the sciences: an inferentialist account.
AB  - I present an alternative account of causation in the biomedical and social
      sciences according to which the meaning of causal claims is given by their
      inferential relations to other claims. Specifically, I will argue that causal
      claims are (typically) inferentially related to certain evidential claims as well
      as claims about explanation, prediction, intervention and responsibility. I
      explain in some detail what it means for a claim to be inferentially related to
      another and finally derive some implication of the proposed account for the
      epistemology, semantics and metaphysics of causation.

PMID- 22883395
TI  - The London field trial for hoarding disorder.
AB  - BACKGROUND: A new diagnostic category, hoarding disorder (HD), has been proposed
      for inclusion in DSM-5. This study field-tested the validity, reliability and
      perceived acceptability of the proposed diagnostic criteria for HD. Method Fifty
      unselected individuals with prominent hoarding behavior and 20 unselected, self
      defined 'collectors' participated in thorough psychiatric assessments, involving
      home visits whenever possible. A semi-structured interview based on the proposed
      diagnostic criteria for HD was administered and scored by two independent raters.
      'True' diagnoses were made by consensus according to the best-estimate diagnosis
      procedure. The percentage of true positive HD cases (sensitivity) and true
      negative HD cases (specificity) was calculated, along with inter-rater
      reliability for the diagnosis and each criterion. Participants were asked about
      their perceptions of the acceptability, utility and stigma associated with the
      new diagnosis. RESULTS: Twenty-nine (58%) of the hoarding individuals and none of
      the collectors fulfilled diagnostic criteria for HD. The sensitivity, specificity
      and inter-rater reliability of the diagnosis, and of each individual criterion
      and the specifiers, were excellent. Most participants with HD (96%) felt that
      creating a new disorder would be very or somewhat acceptable, useful (96%) and
      not too stigmatizing (59%). CONCLUSIONS: The proposed HD criteria are valid,
      reliable and perceived as acceptable and useful by the sufferers. Crucially, they
      seem to be sufficiently conservative and unlikely to overpathologize normative
      behavior. Minor changes in the wording of the criteria are suggested.

PMID- 22883396
TI  - Hypoplasia of the aorta in a patient diagnosed with LMNA gene mutation.
AB  - Hypoplasia of the aorta is a rare entity comprising tubular hypotrophy of a large
      segment of the thoracic and the abdominal aorta. We report for the first time the
      case of a 26-year-old man with Emery-Dreifuss muscular dystrophy presenting
      severe and diffuse hypoplasia of the aorta. 

PMID- 22883397
TI  - Dr. Wu: a beautiful, moving and meditative song -- in memory of Dr. Jing Nuan Wu,
      a pioneer of acupuncture and a Chinese medicine doctor in the United States.

PMID- 22883398
TI  - [Discussion on developing a data management plan and its key factors in clinical
      study based on electronic data capture system].
AB  - Data management has significant impact on the quality control of clinical
      studies. Every clinical study should have a data management plan to provide
      overall work instructions and ensure that all of these tasks are completed
      according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the
      data management plan (DMP) is an auditable document requested by regulatory
      inspectors and must be written in a manner that is realistic and of high quality.
      The significance of DMP, the minimum standards and the best practices provided by
      GCDMP, the main contents of DMP based on electronic data capture (EDC) and some
      key factors of DMP influencing the quality of clinical study were elaborated in
      this paper. Specifically, DMP generally consists of 15 parts, namely, the
      approval page, the protocol summary, role and training, timelines, database
      design, creation, maintenance and security, data entry, data validation, quality
      control and quality assurance, the management of external data, serious adverse
      event data reconciliation, coding, database lock, data management reports, the
      communication plan and the abbreviated terms. Among them, the following three
      parts are regarded as the key factors: designing a standardized database of the
      clinical study, entering data in time and cleansing data efficiently. In the last
      part of this article, the authors also analyzed the problems in clinical research
      of traditional Chinese medicine using the EDC system and put forward some
      suggestions for improvement.

PMID- 22883399
TI  - [Adequate application of quantitative and qualitative statistic analytic methods
      in acupuncture clinical trials].
AB  - Recently, proper use of the statistical methods in traditional Chinese medicine
      (TCM) randomized controlled trials (RCTs) has received increased attention.
      Statistical inference based on hypothesis testing is the foundation of clinical
      trials and evidence-based medicine. In this article, the authors described the
      methodological differences between literature published in Chinese and Western
      journals in the design and analysis of acupuncture RCTs and the application of
      basic statistical principles. In China, qualitative analysis method has been
      widely used in acupuncture and TCM clinical trials, while the between-group
      quantitative analysis methods on clinical symptom scores are commonly used in the
      West. The evidence for and against these analytical differences were discussed
      based on the data of RCTs assessing acupuncture for pain relief. The authors
      concluded that although both methods have their unique advantages, quantitative
      analysis should be used as the primary analysis while qualitative analysis can be
      a secondary criterion for analysis. The purpose of this paper is to inspire
      further discussion of such special issues in clinical research design and thus
      contribute to the increased scientific rigor of TCM research.

PMID- 22883400
TI  - Two-factor designs unable to examine the interactions (part 1).
AB  - Two-factor designs are quite 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 the experimental data under a certain condition (usually it is one of
      the experimental conditions which is formed by the complete combination of the
      levels of two factors) is allowed in specialty, researchers can use random block
      design without repeated experiments, balanced non-complete 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 introduced the first three design types with examples.

PMID- 22883401
TI  - Effects of qigong on performance-related anxiety and physiological stress
      functions in transverse flute music schoolchildren: a feasibility study.
AB  - OBJECTIVE: Based on individual cases of treatment, we were interested in whether
      the effects of a special kind of qigong, the "White Ball" exercises, can be
      objectified by physically measurable parameters and psychological scores.
      METHODS: We performed a preliminary prospective controlled interventional study
      with the waiting list design. In the qigong group eight children were included.
      They received specific qigong lessons of the "White Ball" qigong over seven
      weeks, twice a week, for 30 min with a waiting list design and instructions to
      perform the same exercises at home daily. In the control group eight children
      were included in a waiting list design with no qigong instruction. Subjective
      perception of anxiety was measured by the Portuguese version of the Depression,
      Anxiety and Stress Scale adapted for children. In addition, salivary cortisol,
      heart rate variability, blood pressure, surface electromyography of the trapezius
      muscle and reaction time were measured at the beginning and the end of the study
      prior to the regular public auditions. RESULTS: In comparison to the changes in
      the control group, the qigong group scored significantly lower in heart rate.
      Otherwise the groups did not differ significantly; however, the effect size was
      large for salivary cortisol, surface electromyography of the trapezius muscle and
      blood pressure. There were relevant reductions of subjective perception of
      anxiety, salivary cortisol levels and heart rate. CONCLUSION: The heart rate of
      performing schoolchildren can be potentially reduced by "White Ball" exercises.
      Based on a sample of 8/8, positive tendencies were also observed for anxiety and
      blood pressure. The next steps of objectifying possible qigong effects are to
      increase the sample size, to study young people in other situations arousing
      anxiety, to develop an appropriate control intervention, to solve the problem of
      blinding and double blinding, to find additional parameters that may be
      influenced by the "White Ball" qigong, and to compare the qigong effects with
      other methods reducing anxiety such as more traditional biofeedback or systematic
      desensitization.

PMID- 22883402
TI  - [Traditional Chinese medicine constitution types in 127 elderly patients with
      insomnia: an investigation in communities of Yangpu District, Shanghai].
AB  - OBJECTIVE: To analyze the distribution of traditional Chinese medicine
      constitution types in elderly patients with insomnia. METHODS: The
      epidemiological data were collected from communities in the Yangpu District,
      Shanghai via a cross-sectional field survey. The elderly participants were
      enrolled by using the Pittsburgh Sleep Quality Index (PSQI) scale and the TCM
      Constitution Questionnaire. RESULTS: (1)The distribution of imbalanced
      constitutions between the elderly with insomnia and normal subjects showed
      statistical difference (P<0.01) and the elderly with insomnia tend to be of
      imbalanced constitutions. Among these unbalanced constitutions, deficient
      constitutions were more frequent than others in the elderly with insomnia, and
      yang-deficiency and qi-deficiency occurred mostly in unbalanced and simple
      constitutions. (2) Blood-stasis and qi-stagnation constitutions were more
      frequent in females than in males among the elderly with insomnia. Frequency of
      deficiency constitutions in the elderly increased as the age increases. (3) The
      frequency of composite constitutions was higher than that of simple constitutions
      in elderly patients with insomnia (74.8%), among which qi-deficiency was more
      likely to be composite with other constitutions. CONCLUSION: Identification and
      classification of traditional Chinese medicine constitution types will provide
      further information for devising projects with systematic intervention for
      insomnia management.

PMID- 22883403
TI  - [Effects of electroacupuncture at PC6 and BL15 on nerve electrical activity in
      spinal dorsal root and norepinephrine and dopamine contents in paraventricular
      nucleus of hypothalamus in rats with acute myocardial ischemia].
AB  - OBJECTIVE: To investigate the effects of electroacupuncture (EA) at Neiguan (PC6)
      and Xinshu (BL15) on the nerve electrical activity in spinal dorsal root and
      norepinephrine (NE) and dopamine (DA) concentrations in the paraventricular
      nucleus of the hypothalamus in rats with acute myocardial ischemia (AMI).
      METHODS: A total of 100 male Sprague-Dawley rats were randomly divided into sham
      operation, model, EA at PC6, EA at BL15 and EA at both PC6 and BL15 groups with
      20 rats in each group. The nerve electrical activity in spinal dorsal roots was
      recorded by bipolar electrodes. NE and DA concentrations in the paraventricular
      nucleus of the hypothalamus were detected by high-performance liquid
      chromatography. RESULTS: When compared with the sham-operation group, the nerve
      electrical activity in spinal dorsal roots was significantly increased while the
      NE and DA concentrations in the paraventricular nucleus of the hypothalamus were
      decreased in the model group (P<0.01). The nerve electrical activity in spinal
      dorsal roots was decreased and the NE and DA concentrations were increased in the
      paraventricular nucleus of the hypothalamus in the EA at PC6 group, the EA at
      BL15 group and the EA at both PC6 and BL15 group in comparison to those in the
      model group (P<0.01). The nerve electrical activity in spinal dorsal roots and
      the NE and DA concentrations in paraventricular nucleus of hypothalamus of the EA
      at both PC6 and BL15 group were significantly improved when compared to those of
      the EA at PC6 and EA at BL15 groups (P<0.05). CONCLUSION: EA at both PC6 and BL15
      acupoints exhibits the synergistic protective effects against AMI. The possible
      mechanism is related to regulating the nerve electrical activity in spinal dorsal
      roots and the concentrations of NE and DA in paraventricular nucleus of the
      hypothalamus.

PMID- 22883404
TI  - [Vasodilator effect of oroxylin A on thoracic aorta isolated from rats].
AB  - OBJECTIVE: To investigate the vasodilator effect and the endothelium-dependent
      mechanism of oroxylin A in thoracic aorta isolated from rats. METHODS: Thoracic
      aorta was isolated from Wistar rats. After pretreatment with norepinephrine or
      KCl, the effects of oroxylin A at different concentrations were detected on
      isolated vascular rings prepared from rats' thoracic aorta. The response of
      thoracic aortic ring was evaluated in the presence and absence of endothelium,
      and NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric
      oxide synthase. RESULTS: Oroxylin A (10 and 100 MUmol/L) caused vasodilation on
      endothelium-intact aortic rings pretreated with norepinephrine (1 MUmol/L) and
      KCl (60 mmol/L) compared with the control (P<0.05, P<0.01). The vasodilation
      function of 10 and 100 MUmol/L oroxylin A on the endothelium-denuded aorta rings
      was significantly lower than that on the endothelium-intact aorta rings (P<0.05,
      P<0.01). L-NAME pretreatment significantly attenuated the effect of 100 MUmol/L
      oroxylin A on endothelium-intact aorta rings (P<0.05, P<0.01). CONCLUSION:
      Oroxylin A can induce the relaxation of the aorta ring in endothelium-dependent
      manner. Nitric oxide may be involved in the endothelium-dependent effect of
      oroxylin A.

PMID- 22883405
TI  - [Effects of ursolic acid on c-Cbl-associated protein expression in 3T3-L1
      adipocytes with insulin resistance].
AB  - OBJECTIVE: To observe the effects of ursolic acid (UA) on insulin resistance and
      cell differentiation in 3T3-L1 adipocytes and to explore the mechanisms. METHODS:
      3T3-L1 adipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM)
      supplemented with glucose (25 mmol/L) and insulin (10(-6) mol/L) to induce
      insulin resistance. After culture, glucose consumption of the adipocytes was
      detected by glucose oxidase method and glucose uptake was detected by using
      tritium-marked glucose. Drug concentration for following test was determined
      through detecting the effects of different concentrations of UA on the activity
      of 3T3-L1 adipocytes with insulin resistance by methyl thiazolyl tetrazolium
      (MTT) staining. 3T3-L1 adipocytes with insulin resistance were cultured with
      DMEM, rosiglitazone, and low- and high-dose UA, and then, glucose uptake and
      differentiation of 3T3-L1 adipocytes were detected. Finally, real-time
      fluorescence quantitative polymerase chain reaction and Western blot methods were
      used to detect the effects of UA on expressions of adipocyte lipid binding
      protein (aP2), c-Cbl-associated protein (CAP) and matrix metalloproteinase-1 (MMP
      1) in 3T3-L1 cells with insulin resistance. RESULTS: After dealing with high
      glucose/hyperinsulin for 24 h, insulin resistance was induced successfully in the
      3T3-L1 adipocytes. The concentrations of UA were defined to be 4 to 20 MUmol/L.
      Compared with the model group, the glucose uptake was significantly increased in
      the rosiglitazone group and groups treated with low- and high-dose UA (P<0.01).
      The differentiation levels of 3T3-L1 adipocytes in the UA groups were lower than
      those in the control group and the rosiglitazone group. Effects of UA on the
      expressions of aP2 and MMP-1 were not obvious, but UA could up-regulate
      expression of CAP both in mRNA and protein levels (P<0.01). CONCLUSION: Low- and
      high-dose UA can improve the glycometabolism and differentiation of 3T3-L1
      adipocytes with insulin resistance by up-regulating the expression of CAP.

PMID- 22883406
TI  - [UPLC/Q-TOF-MS-based chemical profiling approach to evaluate the chemical
      constitution of Radix Aconiti Lateralis Preparata in the process of decoction].
AB  - OBJECTIVE: An ultra-performance liquid chromatography coupled with time-of-flight
      mass spectrometry (UPLC/Q-TOF-MS)-based chemical analytic technology was used to
      evaluate the chemical constitution of Radix Aconiti Lateralis Preparata in the
      process of decocting, so as to provide a scientific basis for processing Radix
      Aconiti Lateralis Preparata. METHODS: Radix Aconiti Lateralis Preparata samples
      with different decocting time were detected using UPLC/Q-TOF-MS to create a
      fingerprint spectrum. The data of tR-m/z pairs, ion intensities and sample codes
      were processed by partial least squared-discriminant analysis (PLS-DA) to
      holistically compare the difference among these samples. RESULTS: The contents of
      diester-diterpenoid alkaloid such as aconitine, mesaconitine and hypaconitine
      were higher between 2 to 10 min, while the contents of the lower toxic monoester
      diterpenoid alkaloids such as benzoylaconine, benzoylmesaconine and
      benzoylhypaconine increased during the first 60 min, then their contents
      stabilized. CONCLUSION: Selecting the correct processing time for Radix Aconiti
      Lateralis Preparata according to clinical indications is essential for
      attenuating toxicity and increasing efficiency. Within 30 min is the best time
      for diester-diterpenoid alkaloids as the main pharmacodynamic material, and
      within 60 min is the best time for monoester-diterpenoid alkaloids as the
      pharmacodynamic material of Radix Aconiti Lateralis Preparata.

PMID- 22883407
TI  - [Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on
      pharmacokinetics of oxaliplatin in colon cancer cells].
AB  - OBJECTIVE: To investigate the effects of Changweiqing-medicated serum, which was
      prepared with a compound traditional Chinese herbal medicine, on the reversal of
      oxaliplatin (L-OHP) resistance and the relationship between the reversal and
      cellular accumulation of platinum and proteins associated with copper transporter
      in HCT116/L-OHP cells. METHODS: For clarifying the reversal effect of
      Changweiqing, methyl thiazolyl tetrazolium was applied to determine the L-OHP
      resistance of HCT116/L-OHP cell line. The relationship between the cellular
      accumulation of platinum and the L-OHP resistance in HCT116/L-OHP cells, and the
      effects of drug-medicated serum on intracellular contents of platinum were
      detected by atomic absorption spectrophotometry. Western blot method was used to
      determine the expressions of human copper transporter 1 (hCTR1), ATPase Cu(2+)
      transporting alpha polypeptide (ATP7A), copper-transporting P-type adenosine
      triphosphatase (ATP7B), glutathione S-transferase-pi (GST-pi) and multidrug
      resistance-associated protein 2 (MRP2). RESULTS: The inhibitory concentration 50%
      values of different pairs of L-OHP-sensitive and -resistant cells were 7.2 and
      89.00. The resistance index of HCT116/L-OHP cells was 12.36. The reverse index of
      drug serum on HCT116/L-OHP cells was 2.74. The platinum content in HCT116/L-OHP
      cells was decreased compared with HCT116 cells in condition of 7.2 MUg/mL L-OHP.
      After treating by 7.5% Changweiqing-medicated serum, the intracellular platinum
      contents in L-OHP-sensitive and -resistant cells were increased. It was dose
      dependent that drug-medicated serum promoted the uptake of L-OHP by HCT116 or
      HCT116/L-OHP cells and inhibited the discharge. The 7.5% Changweiqing-medicated
      serum increased the expression of hCTR1 and decreased the expressions of ATP7A
      and ATP7B in HCT116/L-OHP cells, but had no effects on GST-pi and MRP2 protein
      expressions. CONCLUSION: Changweiqing can reverse the L-OHP resistance of
      HCT116/L-OHP by increasing the cellular platinum-DNA accumulation. Down
      regulation of expression of ATP7B and ATP7A, and up-regulation of hCTR1 may cause
      the increase of intracellular platinum content in HCT116/L-OHP cells.

PMID- 22883408
TI  - [Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance
      associated protein 1 expression in hippocampus and cortex of rats with lithium
      pilocarpine-induced epilepsy].
AB  - OBJECTIVE: To study the effects of Xifeng Capsule, a compound traditional Chinese
      herbal medicine, combined with carbamazepine on spontaneous epileptic seizure
      induced by lithium and pilocarpine in rats and the expression level of multidrug
      resistance-associated protein 1 (MRP1). METHODS: Lithium and pilocarpine were
      used to induce epilepsies in rats. All epileptic rats were randomly divided into
      model, high-dose Xifeng Capsule, medium-dose Xifeng Capsule, low-dose Xifeng
      Capsule, high-dose Xifeng Capsule plus carbamazepine (CBZ) (combined high-dose
      group), high-dose Xifeng Capsule plus half dose of CBZ (combined low-dose group)
      and CBZ groups with 10 rats in each group. And another 10 normal rats served as
      control. After treating 28 d, immunohistochemical method was used to detect the
      MRP1 expression in cortex and hippocampus of the epileptic rats. RESULTS: MRP1
      expression in hippocampus of the treated groups was higher than that of the
      normal control group, with wider range and darker positive particles, but was
      lower than that of the model group. In the cortical areas, the differences
      between the combined high-dose group or the combined low-dose group and the model
      group were statistically significant (P<0.05). Regardless of the hippocampus CA1,
      CA3, gyrus or cortical areas, the influence of high-dose Xifeng Capsule on MRP1
      distribution was superior to that of low-dose Xifeng Capsule; Xifeng Capsule
      combined with CBZ had better effects than low-dose Xifeng Capsule, medium-dose
      Xifeng Capsule and CBZ used alone (P<0.05). CONCLUSION: Xifeng Capsule used alone
      or combined with CBZ can effectively inhibit MRP1 expression in hippocampus and
      cortex of epileptic rats.

PMID- 22883409
TI  - [Establishment and evaluation of a rat model of ulcerative colitis with syndrome
      of dampness stagnancy due to spleen deficiency].
AB  - OBJECTIVE: To establish a rat model of ulcerative colitis with syndrome of spleen
      deficiency and dampness stagnancy. METHODS: Sixty rats were divided into normal
      control group, ulcerative colitis group, ulcerative colitis with syndrome of
      spleen deficiency and dampness stagnancy group (model group) and strengthening
      spleen for resolving dampness group. Ulcerative colitis in rats was induced by
      enema containing trinitrobenzene sulfonic acid (TNBS) and ethanol. The rats in
      the model group were suffered from standing in water, limiting sleeping time and
      abnormal diet based on administration of TNBS and ethanol. The rats in the spleen
      strengthening and dampness resolving group were gastrically administered with
      Shenlin Baizhu Powder, a compound traditional Chinese herbal medicine. Symptoms,
      signs and pathological changes in colon tissue of rats were observed after
      modeling. The levels of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha
      (TNF-alpha) in serum of rats were measured by enzyme-linked immunosorbent assay.
      RESULTS: The rats in the model group showed lethargy, poor appetite, loss of
      energy, diarrhea and bloody stool. Their body weight decreased significantly
      compared with the normal control group, and similar changes were found in the
      comparison of food intake, drinking amount, urine amount, stool wet weight and
      assay of spontaneous activity (P<0.05). When observed under a light microscope,
      the colon tissues of rats in the model group showed mucosal edema, congestion,
      inflammatory cell infiltration and ulceration. The degree of colon injury and IL
      6, IL-8 and TNF-alpha levels were significantly increased (P<0.05) as compared to
      those in the normal control group. The changes mentioned above were improved by
      Shenlin Baizhu Powder (P<0.05). CONCLUSION: The rat model of ulcerative colitis
      with syndrome of spleen deficiency and dampness stagnancy is successfully induced
      and has the characteristics of ulcerative colitis of humans both in pathological
      changes and in syndrome.

PMID- 22883410
TI  - [Analysis on content of serum monoamine neurotransmitters in macaques with anger
      in-induced premenstrual syndrome and liver-qi depression syndrome].
AB  - OBJECTIVE: To observe the changes in content of monoamine neurotransmitters in
      the serum of rhesus macaques, and explore the role of serum monoamine
      neurotransmitters in premenstrual syndrome (PMS) and liver-qi depression induced
      by anger-in emotion. METHODS: Social level pressure was applied on 24 female
      macaques to induce the angry emotional reaction, and then nine of the low-status
      macaques with anger-in emotional reaction were screened out and were divided into
      anger-in emotion group, PMS and liver-qi depression group (model group) and
      Jingqianshu Granule group. Macaques in the last two groups were suffered
      extruding in a pack cage for inducing PMS liver-qi depression. After 5 d of
      extruding, experimental animals were evaluated according to the emotional
      evaluation scale, meanwhile, macaque serum of follicular phase and middle-late
      luteal phase was collected to analyze the content of serum norepinephrine,
      dopamine, and 5-hydroxytryptamine. RESULTS: Compared with the normal control
      group, the scores of depression of the model group and the anger-in emotion group
      evaluated with emotional evaluation scale were significantly increased (P<0.01,
      P<0.05); while the score of the model group was significantly higher than that of
      the anger-in emotion group (P<0.05), and it returned to normal after Jingqianshu
      Granule treatment. As compared to the normal control group, serum monoamine
      neurotransmitter levels of the model group and the anger-in emotion group were
      increased (P<0.05, P<0.01), and the serum monoamine neurotransmitter levels of
      the model group were significantly higher than those of the anger-in emotion
      group (P<0.05), while there was no significant difference when compared with the
      normal control group after the treatment. CONCLUSION: Anger-in emotion can induce
      liver-qi depression syndrome which is related to the changes in monoamine
      neurotransmitters.

PMID- 22883411
TI  - Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in
      adjuvant-induced arthritis in rats.
AB  - OBJECTIVE: The present study was designed to investigate the antiperoxidative
      potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced
      arthritis in rats. METHODS: Arthritis was induced by an intradermal injection of
      0.1 mL complete Freund's adjuvant in the foot pad of right hind limb of rats. p
      Coumaric acid (100 mg/kg body weight, intraperitoneally) and the reference drug
      indomethacin (3 mg/kg body weight, intraperitoneally) were administered to
      arthritic rats for 8 d from the 11th day to the 18th day after adjuvant
      injection. The antiperoxidative effect of p-coumaric acid was investigated by
      assessing changes in lipid peroxidation levels and antioxidant status in liver,
      spleen and plasma of the adjuvant-induced arthritic rats. In addition,
      radiological changes in hind limbs of the arthritic rats were also analyzed.
      RESULTS: p-Coumaric acid treatment reversed the altered lipid peroxidation and
      antioxidant status observed in arthritic rats to near normal levels. Soft
      swelling, bone erosion, and joint space narrowing noticed in arthritic rats were
      found to be mitigated in p-coumaric acid-treated arthritic rats. CONCLUSION: The
      study clearly exhibits the antiperoxidative potential of p-coumaric acid against
      adjuvant-induced arthritis in rats.

PMID- 22883412
TI  - Clitorea ternatea, a herb from Indian folklore, improves streptozotocin-induced
      diabetes and diabetes-induced cognitive decline in rats.
AB  - OBJECTIVE: To study the antidiabetic, neurochemical-antioxidant and cognition
      protective effects of Clitorea ternatea leaves on a rat model of diabetic
      cognitive decline. METHODS: Antidiabetic activity was evaluated by serum glucose
      and body weight estimation in ethanol extract of Clitorea ternatea (EECT)-treated
      diabetic rats. Effects of EECT on spatial working memory (SWM) and spatial
      reference memory (SRM) were evaluated by Y-maze and Morris water maze tests
      respectively. Neurochemical-antioxidant effects of EECT were studied by
      acetylcholinesterase assay, and measurements of thiobarbituric acid reactive
      substances (TBARSs), superoxide dismutase (SOD) and catalase (CAT) levels in
      diabetic rats. RESULTS: The 200 and 400 mg/kg of EECT showed a significant
      antidiabetic activity by decreasing serum glucose level (P<0.05, P<0.01), and
      there was a significant increase in the body weight in 400 mg/kg of EECT-treated
      diabetic rats (P<0.01). EECT was found to cause significant increases in SWM and
      SRM in retention trials on Y-maze and Morris water maze respectively (P<0.05,
      P<0.01). Significant decreases in acetylcholinesterase activity and TBARS level,
      and significant increase in CAT level were observed in rats treated with 200 and
      400 mg/kg of EECT compared with rats in the diabetic control group (P<0.05 or
      P<0.01). Significant increase was also found in SOD in rats treated with 400
      mg/kg of EECT. CONCLUSION: Clitorea ternatea exhibits antidiabetic and
      antioxidant activities, offers the protection against diabetes-induced cognitive
      decline, and warrants the need for further studies to elucidate its mode of
      action.

PMID- 22883413
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 4).

PMID- 22883415
TI  - A dual outbreak of bloodstream infections with linezolid-resistant Staphylococcus
      epidermidis and Staphylococcus pettenkoferi in a liver Intensive Care Unit.

PMID- 22883416
TI  - Evaluation of vancomycin serum trough concentrations and outcomes in meticillin
      resistant Staphylococcus aureus bacteraemia.

PMID- 22883414
TI  - Bacterial diversity in the rhizosphere of maize and the surrounding carbonate
      rich bulk soil.
AB  - Maize represents one of the main cultivar for food and energy and crop yields are
      influenced by soil physicochemical and climatic conditions. To study how maize
      plants influence soil microbes we have examined microbial communities that
      colonize maize plants grown in carbonate-rich soil (pH 8.5) using culture
      independent, PCR-based methods. We observed a low proportion of unclassified
      bacteria in this soil whether it was planted or unplanted. Our results indicate
      that a higher complexity of the bacterial community is present in bulk soil with
      microbes from nine phyla, while in the rhizosphere microbes from only six phyla
      were found. The predominant microbes in bulk soil were bacteria of the phyla
      Acidobacteria, Bacteroidetes and Proteobacteria, while Gammaproteobacteria of the
      genera Pseudomonas and Lysobacter were the predominant in the rhizosphere. As
      Gammaproteobacteria respond chemotactically to exudates and are efficient in the
      utilization of plants exudate products, microbial communities associated to the
      rhizosphere seem to be plant-driven. It should be noted that Gammaproteobacteria
      made available inorganic nutrients to the plants favouring plant growth and then
      the benefit of the interaction is common.

PMID- 22883417
TI  - Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative
      disease (PTLD): a Children's Oncology Group Report.
AB  - Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains
      problematic. A phase II trial adding rituximab to a low-dose cyclophosphamide and
      prednisone regimen was conducted for pediatric patients with Epstein-Barr virus
      (EBV) (+), CD20 (+) PTLD. Fifty-five patients were enrolled. Toxicity was similar
      for cycles of therapy containing rituximab versus those without. The complete
      remission (CR) rate was 69% (95% confidence interval (CI); 57%-84%). Of 12
      patients with radiographic evidence of persistent disease at the end of therapy,
      eight were in CR 28 weeks later without further PTLD therapy. There were 10
      deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2-year
      event-free survival (alive with functioning original allograft and no PTLD) was
      71% (95% CI: 57%-82%) and overall survival was 83% (95% CI: 69%-91%) with median
      follow-up of 4.8 years. Due to small numbers, we were unable to determine
      significance of tumor histology, stage of disease, allograft type or early
      response to treatment on outcome. These data suggest rituximab combined with low
      dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD
      following solid-organ transplantation.

PMID- 22883418
TI  - Incidence and acute complications of asymptomatic central venous catheter-related
      deep venous thrombosis in critically ill children.
AB  - OBJECTIVE: To determined the current incidence and acute complications of
      asymptomatic central venous catheter (CVC)-related deep venous thrombosis (DVT)
      in critically ill children. STUDY DESIGN: We performed a prospective cohort study
      in 3 pediatric intensive care units. A total of 101 children with newly inserted
      untunneled CVC were included. CVC-related DVT was diagnosed using compression
      ultrasonography with color Doppler. RESULTS: Asymptomatic CVC-related DVT was
      diagnosed in 16 (15.8%) children, which equated to 24.7 cases per 1000 CVC-days.
      Age was independently associated with DVT. Compared with children aged <1 year,
      children aged >13 years had significantly higher odds of DVT (aOR, 14.1, 95% CI,
      1.9-105.8; P = .01). Other patient demographics, interventions (including
      anticoagulant use), and CVC characteristics did not differ between children with
      and without DVT. Mortality-adjusted duration of mechanical ventilation, a
      surrogate for pulmonary embolism, was statistically similar in the 2 groups (22
      +/- 9 days in children with DVT vs 23 +/- 7 days in children without DVT; P =
      .34). Mortality-adjusted intensive care unit and hospital lengths of stay also
      were similar in the 2 groups. CONCLUSION: Asymptomatic CVC-related DVT is common
      in critically ill children. However, the acute complications do not seem to
      differ between children with and without DVT. Larger studies are needed to
      confirm these results. Future studies should also investigate the chronic
      complications of asymptomatic CVC-related DVT.

PMID- 22883420
TI  - A boy with acute strabismus.

PMID- 22883419
TI  - Hepatitis C virus-specific cell-mediated immune responses in children born to
      mothers infected with hepatitis C virus.
AB  - OBJECTIVE: To investigate the association between hepatitis C virus (HCV)
      specific cell-mediated immunity (CMI) responses and viral clearance in children
      born to mothers infected with HCV. STUDY DESIGN: A cross-sectional study of
      children from a mother-infant cohort in Egypt were enrolled to detect CMI
      responses to recombinant core and nonstructural HCV antigens (nonstructural
      segments NS3, NS4a/b, and NS5 of the HCV genome) using an interferon-gamma enzyme
      linked immunospot assay. Children born to mothers with chronic HCV were enrolled
      into 3 groups: transiently viremic (n = 5), aviremic (n = 36), and positive
      control (n = 6), which consisted of 1 child with chronic HCV from this cohort and
      another 5 children with chronic HCV from a companion study. Children without HCV
      born to mothers without HCV (n = 27) served as a negative control group. Wilcoxon
      rank sum test was used to compare the magnitude of CMI responses between groups.
      RESULTS: None of the 6 control children who were positive for HCV responded to
      any HCV antigen, and 4 (80%) of 5 children with transient viremia responded to at
      least one HCV antigen, compared with 5 (14%) of 36 and 3 (11%) of 27 children in
      the aviremic and negative control groups, respectively. Children with transient
      viremia elicited stronger responses than did negative controls (P = .005),
      positive controls (P = .011), or children without HCV viremia (P = .012),
      particularly to nonstructural antigens. CONCLUSIONS: HCV-specific CMI responses
      were significantly higher in magnitude and frequency among transiently infected
      children compared with those persistently infected. This suggests CMI responses
      may be associated with past viral clearance and can identify children at high
      risk of infection, who can be targeted for health education, screening, and
      follow-up.

PMID- 22883421
TI  - Prospective randomized crossover evaluation of three anesthetic regimens for
      painful procedures in children with cancer.
AB  - OBJECTIVE: To identify the most effective sedation regimen for bone marrow
      aspiration and lumbar puncture procedures with a prospective trial of 3
      combinations of sedation/analgesia. STUDY DESIGN: In this double-blind crossover
      study, we randomly assigned 162 children with acute lymphoblastic leukemia or
      lymphoblastic lymphoma to receive fentanyl 1 mcg/kg, fentanyl 0.5 mcg/kg, or
      placebo, in addition to propofol and topical anesthetic for 355 procedures.
      RESULTS: We found no significant differences among the 3 regimens in the
      frequency of pain (pain score > 0) or severe pain (pain score >= 5) during
      recovery, or a >20% increase in hemodynamic/respiratory variables during
      anesthesia. Treatment with fentanyl 1 mcg/kg was associated with a lower
      frequency of movement during procedure compared with treatment with fentanyl 0.5
      mcg/kg (P = .0476) or treatment with placebo (P = .0545). The placebo group
      required longer time to recover (median, 18 minutes) compared with the fentanyl
      0.5 mcg/kg group (median, 9 minutes) (median difference 2.0, P = .007) and the
      fentanyl 1 mcg/kg (median 8 minutes), (median difference 2.0, P = .15). The
      placebo group also required larger total dose of propofol (median 5 mg/kg)
      compared with that of the fentanyl 1 mcg/kg group (median, 3.5 mg/kg) and the
      fentanyl 0.5 mcg/kg group (median 3.5 mg/kg) (median differences 1.5, P < .00005,
      in both comparisons). CONCLUSION: The addition of fentanyl 1 mcg/kg to propofol
      for brief painful procedures reduces movement, propofol dose, and recovery time.

PMID- 22883422
TI  - Key outcomes from stakeholder workshops at a symposium to inform the development
      of an Australian national plan for rare diseases.
AB  - BACKGROUND: Calls have been made for governments to adopt a cohesive approach to
      rare diseases through the development of national plans. At present, Australia
      does not have a national plan for rare diseases. To progress such a plan an
      inaugural Australian Rare Diseases Symposium was held in Western Australia in
      April 2011. This paper describes the key issues identified by symposium attendees
      for the development of a national plan, compares these to the content of EUROPLAN
      and national plans elsewhere and discusses how the outcomes might be integrated
      for national planning. METHODS: The symposium was comprised of a series of
      plenary sessions followed by workshops. The topics covered were; 1) Development
      of national plans for rare diseases; 2) Patient empowerment; 3) Patient care,
      support and management; 4) Research and translation; 5) Networks, partnerships
      and collaboration. All stakeholders within the rare diseases community were
      invited to participate, including: people affected by rare diseases such as
      patients, carers, and families; clinicians and allied health practitioners;
      social and disability services; researchers; patient support groups; industry
      (e.g. pharmaceutical, biotechnology and medical device companies); regulators and
      policy-makers. RESULTS: All of these stakeholder groups were represented at the
      symposium. Workshop participants indicated the need for a national plan, a
      national peak body, a standard definition of 'rare diseases', education
      campaigns, lobbying of government, research infrastructure, streamlined whole-of
      lifetime service provision, case co-ordination, early diagnosis, support for
      health professionals and dedicated funding. CONCLUSIONS: These findings are
      consistent with frameworks and initiatives being undertaken internationally (such
      as EUROPLAN), and with national plans in other countries. This implies that the
      development of an Australian national plan could plausibly draw on frameworks for
      plan development that have been proposed for use in other jurisdictions. The
      translation of the symposium outcomes to government policy (i.e. a national plan)
      requires the consideration of several factors such as the under-representation of
      some stakeholder groups (e.g. clinicians) and the current lack of evidence
      required to translate some of the symposium outcomes to policy options. The
      acquisition of evidence provides a necessary first step in a comprehensive
      planning approach.

PMID- 22883423
TI  - Characterization of microRNA expression profiles in normal and osteoarthritic
      human chondrocytes.
AB  - BACKGROUND: Osteoarthritis (OA) is a multifactorial disease characterized by
      destruction of the articular cartilage due to environmental, mechanical and
      genetic components. The genetics of OA is complex and is not completely
      understood. Recent works have demonstrated the importance of microRNAs (miRNAs)
      in cartilage function. MiRNAs are a class of small noncoding RNAs that regulate
      gene expression and are involved in different cellular process: apoptosis,
      proliferation, development, glucose and lipid metabolism. The aim of this study
      was to identify and characterize the expression profile of miRNAs in normal and
      OA chondrocytes and to determine their role in the OA. METHODS: Chondrocytes were
      moved to aggregate culture and evaluated using histological and qPCR techniques.
      miRNAs were isolated and analyzed using the Agilent Human miRNA Microarray.
      RESULTS: Of the 723 miRNAs analyzed, 7 miRNAs showed a statistically significant
      differential expression. Amongst these 7 human miRNAs, 1 was up-regulated in OA
      chondrocytes (hsa-miR-483-5p) and 6 were up-regulated in normal chondrocytes (hsa
      miR-149*, hsa-miR-582-3p, hsa-miR-1227, hsa-miR-634, hsa-miR-576-5p and hsa-miR
      641). These profiling results were validated by the detection of some selected
      miRNAs by qPCR. In silico analyses predicted that key molecular pathways
      potentially altered by the miRNAs differentially expressed in normal and OA
      chondrocytes include TGF-beta, Wnt, Erb and mTOR signalling; all of them
      implicated in the development, maintenance and destruction of articular
      cartilage. CONCLUSIONS: We have identified 7 miRNAs differentially expressed in
      OA and normal chondrocytes. Our potential miRNA target predictions and the
      signalling cascades altered by the differentially expressed miRNAs supports the
      potential involvement of the detected miRNAs in OA pathology. Due to the
      importance of miRNA in mediating the translation of target mRNA into protein, the
      identification of these miRNAs differentially expressed in normal and OA
      chondrocyte micropellets could have important diagnostic and therapeutic
      potential. Further studies are needed to know the function of these miRNAs,
      including the search of their target mRNA genes, which could lead to the
      development of novel therapeutic strategies for the OA treatment.

PMID- 22883424
TI  - An indirect comparison of the efficacy and safety of desvenlafaxine and
      venlafaxine using placebo as the common comparator.
AB  - BACKGROUND: This meta-analysis compared the efficacy and safety of desvenlafaxine
      and venlafaxine at the Australian approved doses. METHODS: A systematic
      literature search was conducted to identify all placebo-controlled studies of
      desvenlafaxine and venlafaxine in the treatment of major depression. The pivotal
      outcome measure used to assess comparative efficacy was the mean change in
      Hamilton Rating Scale for Depression-17 score from baseline. Tolerability and
      safety were compared by an evaluation of reported adverse events. Standard and
      Bayesian methods were used to conduct the indirect comparisons. Findings Using a
      mixed model repeated measures analysis, the pooled weighted mean difference for
      the mean change in Hamilton Rating Scale for Depression-17 score from baseline
      was -2.81 (-3.72, -1.91; p < 0.001) for desvenlafaxine and -2.61 (-3.17, -2.05; p
      < 0.001) for venlafaxine. An indirect Bayesian analysis adjusted for baseline
      Hamilton Rating Scale for Depression-17 score showed no significant difference
      between the two treatments (weighted mean difference -0.27; -1.17, 0.65). A
      standard indirect comparison of any adverse events showed no significant
      difference between desvenlafaxine and venlafaxine (relative risk 1.01; 0.96,
      1.06; p = 0.70 and risk difference -0.01; -0.05, 0.03; p = 0.59). Standard
      indirect comparisons of both nausea and drop-outs identified potential
      differences between treatments, with the risk difference analyses suggesting a
      trend in favor of desvenlafaxine (nausea: relative risk 0.97; 0.77, 1.22; p =
      0.80/RD -0.07; -0.12, -0.01; p = 0.02; and drop-outs due to adverse events: RR
      0.86; 0.58, 1.29; p = 0.48/RD -0.04; -0.08, 0.00; p = 0.06). CONCLUSIONS: Based
      on the results of this meta-analysis, desvenlafaxine was shown to be non-inferior
      to venlafaxine in terms of efficacy, and has an advantage in terms of less
      nausea.

PMID- 22883425
TI  - Does back and neck pain become more common as you get older? A systematic
      literature review.
AB  - BACKGROUND: It is generally believed that the prevalence of back pain increases
      with age and as the proportion of elderly will keep rising we may be facing
      serious public health concerns in the future. AIM: The aim of this systematic
      literature review is to establish whether back pain (i.e. neck, mid-back and/or
      low back pain) becomes increasingly common in the older population, specifically
      to study 1) whether there is a significant increase in the prevalence of back
      pain after middle age, and 2) whether there is a significant gradually increasing
      prevalence of back pain with continued old age. METHODS: A systematic literature
      search was conducted in Pubmed on articles in English, published between January
      2000 and July 2011. Non-clinical studies from the developed countries with
      prevalence estimates on elderly people (60+) on any type of self-reported back
      pain and on different age groups with adequate sample sizes were included in the
      review. The included articles were extracted for information by two independent
      reviewers. RESULTS: A total of 12 articles were included covering the entire
      spine. Neck pain was studied nine times, low back pain eight times, back pain
      three times, upper back two times and neck/shoulders once. All studies showed no
      significant increase of back pain with age, neither when passing from middle age
      (i.e. 45+ years of age) into the sixties, nor later in life. In contrast, most
      studies reported a decline for the oldest group. CONCLUSIONS: Back pain is no
      more common in the elderly population (>60 years) when compared to the middle age
      population. Back pain does not increase with increasing age, but seems to decline
      in the oldest people.

PMID- 22883426
TI  - Low-temperature synthesis of multilayer graphene/amorphous carbon hybrid films
      and their potential application in solar cells.
AB  - The effect of reaction temperature on the synthesis of graphitic thin film on
      nickel substrate was investigated in the range of 400 degrees C to 1,000 degrees
      C. Amorphous carbon (a-C) film was obtained at 400 degrees C on nickel foils by
      chemical vapor deposition; hybrid films of multilayer graphene (MLG) and a-C were
      synthesized at a temperature of 600 degrees C, while MLG was obtained at
      temperatures in excess of 800 degrees C. Schottky-junction solar cell devices
      prepared using films produced at 400 degrees C, 600 degrees C, 800 degrees C, and
      1,000 degrees C coupled with n-type Si demonstrate power conversion efficiencies
      of 0.003%, 0.256%, 0.391%, and 0.586%, respectively. A HNO3 treatment has further
      improved the efficiencies of the corresponding devices to 0.004%, 1.080%, 0.800%,
      and 0.820%, respectively. These films are promising materials for application in
      low-cost and simple carbon-based solar cells.

PMID- 22883427
TI  - [Neurosurgery: roadmap].

PMID- 22883428
TI  - Aberrant intrinsic brain activity and cognitive deficit in first-episode
      treatment-naive patients with schizophrenia.
AB  - BACKGROUND: Given the important role of the default mode network (DMN) in
      cognitive function and the well-known neurocognitive deficit in schizophrenia, it
      is intriguing to examine systematically the relationship between neurocognitive
      dysfunction and aberrant intrinsic activities, and also functional connectivity,
      of the DMN in patients with schizophrenia. Method First-episode, treatment-naive
      patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113)
      underwent resting-state functional magnetic resonance imaging (fMRI) scans and
      neurocognitive tests. Intrinsic neural activities evaluated by using the fragment
      amplitude of low-frequency fluctuations (fALFF) and the resting-state functional
      connectivity assessed by seed-based correlational analysis were compared between
      patients and controls. Aberrant intrinsic activities and DMN connectivity in
      patients were then correlated to neurocognitive performance and clinical
      symptoms. RESULTS: Compared to controls, patients with FES showed decreased fALFF
      in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex
      (OFC), and increased fALFF in the bilateral putamen. Increased functional
      connectivity with the DMN was observed in the left insula and bilateral
      dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the
      bilateral OFC were correlated with cognitive processing speed; fALFF in the left
      OFC and right putamen were correlated with the clinical factors
      excited/activation and disorganization; and increased DMN functional connectivity
      in the left insula was correlated with the clinical factors positive,
      excited/activation, disorganization and neurocognitive deficit in the domain of
      sustained attention. CONCLUSIONS: These associations between neurocognitive
      dysfunction and aberrant intrinsic activities, and also functional connectivity,
      of the DMN in patients with schizophrenia may provide important insights into the
      neural mechanism of the disease.

PMID- 22883429
TI  - Short-term results of laparoscopic surgery after preoperative chemoradiation for
      clinically staged T3 and T4 rectal cancer.
AB  - INTRODUCTION: The feasibility of laparoscopic surgery for clinically staged T3
      and T4 rectal cancer has not been clearly defined specifically in cases following
      preoperative chemoradiation therapy (CRT). Our aim was to investigate the
      feasibility of laparoscopic surgery after preoperative CRT for clinically staged
      T3 and T4 rectal cancer. METHODS: Between May 2003 and June 2009, 57 patients
      (T3: n = 50, T4: n = 7) who underwent preoperative CRT for rectal cancer were
      identified. Forty-three patients with laparoscopic surgery (Lap group) were
      compared with 14 patients who underwent open surgery (Open group). Perioperative
      data including postoperative morbidity were assessed between the two groups.
      RESULTS: All patients underwent complete laparoscopic operations, and none was
      converted to laparotomy. Operating time was longer in the Open group (331 vs 375
      min, P < 0.01). Blood loss was lower in the Lap group (160 vs 316 mL, P < 0.01).
      Lymph node harvest and morbidity rate were similar in both groups. The distal
      tumor margin was negative in all patients. No patients had perioperative
      mortality associated with surgery after CRT. CONCLUSION: Laparoscopic surgery
      after preoperative CRT is a feasible and a safe option for T3 and T4 rectal
      cancer compared to conventional open surgery.

PMID- 22883430
TI  - Hemodynamic and electrophysiological connectivity in the language system:
      simultaneous near-infrared spectroscopy and electrocorticography recordings
      during cortical stimulation.
AB  - We applied near-infrared spectroscopy (NIRS) and electrocorticography (ECoG)
      recordings during cortical stimulation to a temporal lobe epilepsy patient who
      underwent subdural electrode implantation. Using NIRS, changes in blood
      concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HbR) during
      cortical stimulation of the left language areas were measured in each hemisphere.
      NIRS revealed that 2 Hz stimulation with 5 mA produced no significant hemodynamic
      changes in either hemisphere. By contrast, 50 Hz stimulation elicited significant
      increases in both HbO(2) and HbR at the stimulation site. Furthermore, with 50 Hz
      stimulation of the left superior temporal gyrus, the increases in HbO(2) and HbR
      were observed not only at the stimulation site but also concurrently at the left
      inferior frontal gyrus. This suggests the existence of functional connectivity in
      the language system. The present study demonstrates that simultaneous NIRS and
      ECoG studies during cortical stimulation allow a novel analysis of cerebral
      connectivity.

PMID- 22883431
TI  - Improved HIV-related outcomes associated with implementation of a novel public
      health information exchange.
AB  - PURPOSE: The purpose of this study was to evaluate HIV-related outcomes
      associated with use of a novel public health information exchange that was
      designed to identify out of care HIV-infected individuals seen within a large,
      integrated delivery network (IDN). METHODS: A novel, secure, bidirectional health
      care delivery-public health information exchange, the Louisiana Public Health
      Information Exchange (LaPHIE) was developed between a multi-geographical IDN and
      the Louisiana public health authority in response to the high proportion of out
      of care HIV-infected persons. The system provides real-time provider alerts when
      any HIV-infected person who has not had CD4 or HIV viral load (VL) monitoring in
      >1 year receives non-HIV care within the IDN, allowing immediate linkage to HIV
      specialty care. Persons identified over the first 30 months of the system's
      implementation were characterized using a case-cohort approach to compare out-of
      care individuals with randomly sampled, time-matched in-care controls. RESULTS:
      Between 2/1/09 and 7/31/11, 549 alerts identified 419 unduplicated HIV-infected
      individuals without a CD4 count or VL in >1 year. Patients were identified at 60
      clinics and alerts shown to 223 clinicians in 7 participating facilities. A
      quarter (24%) of those identified had not had a CD4 count or VL conducted since
      their initial diagnosis. Of the remaining 76% who had been in care previously,
      over half (55%) had been out of care for >=18 months, with a median time of 19.4
      months [IQR 15.0-32.5] since their previous visit. Following LaPHIE
      identification, 42% had CD4 counts<200 cells/mm(3) and 62% had VL>10,000 RNA
      copies/mL. Of the 344 patients with at least 6 months of follow up, 85% had at
      least one CD4 and/or VL test after being identified. CONCLUSIONS: The results of
      this study demonstrate that an information exchange can effectively facilitate
      engagement, re-engagement, and retention of out-of care HIV-infected persons in
      HIV specialty care. Within two years, we were able to observe significant
      improvements in HIV-related utilization and disease progression indices. Future
      programs should consider adopting this innovative strategy to improve HIV care at
      both the individual and population levels.

PMID- 22883432
TI  - A partial MECP2 duplication in a mildly affected adult male: a putative role for
      the 3' untranslated region in the MECP2 duplication phenotype.
AB  - BACKGROUND: Duplications of the X-linked MECP2 gene are associated with moderate
      to severe intellectual disability, epilepsy, and neuropsychiatric illness in
      males, while triplications are associated with a more severe phenotype. Most
      carrier females show complete skewing of X-inactivation in peripheral blood and
      an apparent susceptibility to specific personality traits or neuropsychiatric
      symptoms. METHODS: We describe the clinical phenotype of a pedigree segregating a
      duplication of MECP2 found on clinical array comparative genomic hybridization.
      The position, size, and extent of the duplication were delineated in peripheral
      blood samples from affected individuals using multiplex ligation-dependent probe
      amplification and fluorescence in situ hybridization, as well as targeted high
      resolution oligonucleotide microarray analysis and long-range PCR. The molecular
      consequences of the rearrangement were studied in lymphoblast cell lines using
      quantitative real-time PCR, reverse transcriptase PCR, and western blot analysis.
      RESULTS: We observed a partial MECP2 duplication in an adult male with epilepsy
      and mild neurocognitive impairment who was able to function independently; this
      phenotype has not previously been reported among males harboring gains in MECP2
      copy number. The same duplication was inherited by this individual's daughter who
      was also affected with neurocognitive impairment and epilepsy and carried an
      additional copy-number variant. The duplicated segment involved all four exons of
      MECP2, but excluded almost the entire 3' untranslated region (UTR), and the
      genomic rearrangement resulted in a MECP2-TEX28 fusion gene mRNA transcript.
      Increased expression of MECP2 and the resulting fusion gene were both confirmed;
      however, western blot analysis of lysates from lymphoblast cells demonstrated
      increased MeCP2 protein without evidence of a stable fusion gene protein product.
      CONCLUSION: The observations of a mildly affected adult male with a MECP2
      duplication and paternal transmission of this duplication are unique among
      reported cases with a duplication of MECP2. The clinical and molecular findings
      imply a minimal critical region for the full neurocognitive expression of the
      MECP2 duplication syndrome, and suggest a role for the 3' UTR in mitigating the
      severity of the disease phenotype.

PMID- 22883434
TI  - Context-induced relapse to alcohol seeking after punishment in a rat model.
AB  - BACKGROUND: Rat studies have demonstrated that exposure to environments
      associated with alcohol intake reinstates alcohol seeking after extinction of
      alcohol-reinforced responding in a different context. However, extinction is
      limited as an abstinence model, because humans typically abstain because of
      negative consequences associated with excessive drinking. It is currently unknown
      whether alcohol-associated contexts can provoke relapse to alcohol seeking after
      alcohol-taking behavior is suppressed by adverse consequences in a different
      context. METHODS: Alcohol-preferring P rats were first given home-cage access to
      20% ethanol. Next, they were trained to self-administer 20% ethanol in one
      context (context A). Subsequently, all rats continued to self-administer alcohol
      in a different context (context B). For one group, 50% of alcohol-reinforced
      responses were punished by mild footshock; two other groups either received
      noncontingent shocks or no shock. A fourth group was given extinction training in
      context B. All rats were then tested for relapse to alcohol seeking under
      extinction conditions in contexts A and B. RESULTS: In Context B, alcohol-taking
      behavior was suppressed by contingent shock (punishment) and extinction training
      but not by noncontingent shock. In Context A, relapse to alcohol seeking was
      reliably observed in the punished and extinction groups; a context switch had no
      effect on alcohol seeking in the no-shock or noncontingent shock groups.
      CONCLUSIONS: Our data indicate that punishment-induced suppression of alcohol
      taking behavior is context-dependent. We propose that our procedure can be used
      to explore mechanisms of context-induced relapse to alcohol seeking after alcohol
      taking behavior is suppressed by adverse consequences.

PMID- 22883435
TI  - The reflective statement: a new tool to assess resident learning.
AB  - PURPOSE: Continued assessment and redesign of the curriculum is essential for
      optimal surgical education. For the last 3 y, we have asked the residents to
      reflect on the previous week and describe "the best thing" they learned. We
      hypothesize that this statement could be used to assess the weaknesses or
      strengths of our curriculum. METHODS: Starting in 2007, residents filled out
      surveys approximately 4 times/y at the start of a mandatory conference. They were
      asked to describe the "best thing" they learned that week, where it was learned,
      and who taught it. Residents were not asked to classify the item learned by core
      competency (communication, knowledge, patient care, practice-based learning,
      professionalism, and systems-based practice). This categorization into core
      competencies was done as part of our study design. Attending, fellow, resident,
      or other were used as groups designating who taught each item. Where the item was
      learned was fit into either clinic, conference, operating room (OR), wards, or
      self. The impact of postgraduate year (PGY) level on learning was also assessed.
      chi(2) analysis was used to compare groups. RESULTS: During the study period, 304
      surveys were completed and returned by 65 residents. The majority of responses
      came from PGY 1 residents (134, 43%). Patient care and knowledge were the most
      common core competencies learned. As PGY level increased, learning of
      professionalism (P = 0.035) increased. A majority of learning was experiential
      (wards and OR, P < 0.0125). Self-learning and learning in clinic was a minor
      component of learning (P < 0.0125). Learning on wards (P < 0.001) decreased as
      residents progressed and learning from the OR (P = 0.002) had the opposite trend.
      CONCLUSIONS: Patient care and knowledge are the most frequently cited
      competencies learned by the residents. Self-learning is not a significant source
      of learning, and the majority of the learning is experiential. It is not known if
      this was a sign that there was a lack of self-directed learning or that self
      directed learning was not an efficient method of learning. In addition, each PGY
      level learns differently (teacher and location of learning), perhaps reflecting
      the different needs and/or structure of each PGY. We believe the reflective
      statement has been and will be a useful tool to assess our curriculum.

PMID- 22883433
TI  - Genome-wide association study implicates HLA-C*01:02 as a risk factor at the
      major histocompatibility complex locus in schizophrenia.
AB  - BACKGROUND: We performed a genome-wide association study (GWAS) to identify
      common risk variants for schizophrenia. METHODS: The discovery scan included 1606
      patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or
      imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270
      cases and 860 controls) was subsequently included in the Psychiatric GWAS
      Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were
      taken forward for replication in an independent sample of 13,195 cases and 31,021
      control subjects. The most significant associations in discovery, corrected for
      genomic inflation, were (rs204999, p combined = 1.34 * 10(-9) and in combined
      samples (rs2523722 p combined = 2.88 * 10(-16)) mapped to the major
      histocompatibility complex (MHC) region. We imputed classical human leukocyte
      antigen (HLA) alleles at the locus; the most significant finding was with HLA
      C*01:02. This association was distinct from the top SNP signal. The HLA alleles
      DRB1*03:01 and B*08:01 were protective, replicating a previous study.
      CONCLUSIONS: This study provides further support for involvement of MHC class I
      molecules in schizophrenia. We found evidence of association with previously
      reported risk alleles at the TCF4, VRK2, and ZNF804A loci.

PMID- 22883436
TI  - The timing of established detrusor hyperreflexia in a rat model of neuropathic
      bladder.
AB  - BACKGROUND: Proper timing of catheter insertion and the use of a suitable
      surgical method are essential parts of producing rat models to evaluate
      neuropathic bladder following spinal cord injury (SCI). METHODS: Thirty-two
      female Sprague-Dawley rats were randomly allocated into four groups. Group 1
      underwent surgical laminectomy using the classic method. Group 2 underwent SCI 7
      d following insertion of the catheter, and group 3 underwent sham operation. For
      bladder catheterization, a 4.5 Fr catheter was fixed into the bladder and
      tunneled beneath the skin to reach out at the nape of the neck. Group 4 underwent
      urodynamic study via bladder catheter prior to surgery and every 10 d following
      the operation to determine the exact time of establishing neuropathic bladder
      following spinal shock. The animals' survival rate and bladder wall's
      histopathologic changes were assessed 30 d following the operation. RESULTS:
      Simultaneous suprapubic catheter placement raised the mortality rate in group 1
      in comparison with group 2. Repeated urodynamic study in group 4 showed
      hypertonic behavior in the bladder 10 d after SCI, with significantly increased
      leak point pressure and bladder capacity; however, the end filling pressure and
      constant neuropathic bladder on cystometric indices are attained from 20 d after
      the operation. CONCLUSIONS: Insertion of a bladder catheter 1 wk prior to SCI
      provides an applicable route for repeated cystometric studies in rats. The
      results demonstrate that sustained bladder overactivity is established in rats 20
      d after SCI and animals are ready for further experiments on neuropathic bladder
      dysfunction following this period.

PMID- 22883437
TI  - Pulmonary impact of N-acetylcysteine in a controlled hemorrhagic shock model in
      rats.
AB  - BACKGROUND: Experimental hemorrhagic shock (HS) is based on controlling bleeding
      and the treatment of fluid resuscitation to restore tissue oxygenation and
      perfusion. The HS could promote ischemia/reperfusion injury, which induces a
      general exacerbation of the inflammatory process, initially compromising the
      lungs. N-acetylcysteine (NAC), an antioxidant, may attenuate ischemia/reperfusion
      injury. This study evaluated the effect of NAC in association with fluid
      resuscitation on pulmonary injury in a controlled HS model in rats. METHODS: Male
      Wistar rats were submitted to controlled HS (mean arterial pressure of 35 mm Hg
      for 60 min). Two groups were constituted according to resuscitation solution
      administered: RLG (Ringer's lactate solution) and RLG+NAC (Ringer's lactate in
      association with 150 mg/kg NAC. A control group was submitted to catheterization
      only. After 120 min of resuscitation, bronchoalveolar lavage was performed to
      assess intra-alveolar cell infiltration and pulmonary tissue was collected for
      assessment of malondialdehyde, interleukin 6, and interleukin 10 and
      histopathology. RESULTS: Compared with the RLG group, the RLG+NAC group showed
      lower bronchoalveolar lavage inflammatory cell numbers, lower interstitial
      inflammatory infiltration in pulmonary parenchyma, and lower malondialdehyde
      concentration. However, tissue cytokine (interleukin 6 and interleukin 10)
      expression levels were similar. CONCLUSION: N-acetylcysteine was associated with
      fluid resuscitation-attenuated oxidative stress and inflammatory cell
      infiltration in pulmonary parenchyma. N-acetylcysteine did not modify cytokine
      expression.

PMID- 22883438
TI  - The role of the Janus kinase family/signal transducer and activator of
      transcription signaling pathway in fibrotic renal disease.
AB  - Over the past several years, a number of cytokines and growth factors including
      transforming growth factor beta1, tumor necrosis factor alpha, and angiotensin II
      have been shown to play a crucial role in renal fibrosis. The Janus kinase family
      (JAK) and signal transducers and activators of transcription (STATs) constitute
      one of the primary signaling pathways that regulate cytokine expression, and the
      JAK/STAT signaling pathway has increasingly been implicated in the
      pathophysiology of renal disease. This review examines the role of the JAK/STAT
      signaling pathway in fibrotic renal disease. The JAK/STAT signaling pathway is
      activated in a variety of renal diseases and has been implicated in the
      pathophysiology of renal fibrosis. Experimental evidence suggests that inhibition
      of the JAK/STAT signaling pathway, in particular JAK2 and STAT3, may suppress
      renal fibrosis and protect renal function. However, it is incompletely understood
      which cells activate the JAK/STAT signaling pathway and which JAK/STAT signaling
      pathway is activated in each renal disease. Research regarding JAK/STAT signaling
      and its contribution to renal disease is still ongoing in humans. Future studies
      are required to elucidate the potential role of JAK/STAT signaling inhibition as
      a therapeutic strategy in the attenuation of renal fibrosis.

PMID- 22883439
TI  - Treatment of dairy cows with PGF2alpha or NSAID, in combination with antibiotics,
      in cases of postpartum uterine inflammation.
AB  - BACKGROUND: The aim of the study was to test the effect of two treatments in
      cases of acute puerperal metritis (APM) and clinical metritis (CM). METHODS: Cows
      with APM and CM (n = 40)) were matched according to plasma fibrinogen levels (Fb)
      into three groups. Two negative control groups D (n = 11) and E (n = 17) were
      composed of healthy cows. The proportion of animals with APM and CM was similar
      within the groups. Treatment was started on the 3rd day postpartum (PP). In group
      A (n = 15), intramuscular (i.m.) administration of ceftiofur was used for five
      days in combination with flunixin for three days. Group B (n = 15) received i.m.
      administration of ceftiofur for five days followed by two injections of
      prostaglandin F2alpha, with an interval of 8 h, on the 8th day PP. Group C (n =
      10) served as a control group with no treatment. The general health status, body
      temperature (BT) and vaginal discharge were evaluated daily. Endometrial biopsies
      for bacteriology were taken once a week for seven weeks PP. Blood samples for the
      analysis of acute phase proteins were collected once a week for six weeks PP.
      Samples for progesterone analysis were taken twice a week for seven weeks PP.
      Fertility performance data were recorded. RESULTS: The area under the curve of BT
      was higher in group B than in group D cows (P < 0.05). No differences were found
      for vaginal discharge. There were no differences in bacterial growth, start of
      ovarian activity or serum amyloid-A or fibrinogen levels among the groups. The
      haptoglobin concentration was higher in the first and second weeks PP in group B
      compared with the other groups (P < 0.05). The number of days open was higher in
      group A than in both groups B and D (P < 0.05). The pregnancy rate after the
      first two services was higher (P < 0.05) in groups B and D than in groups A and
      C. The number of services per pregnancy was lower in group B than in group C (P <
      0.05). CONCLUSIONS: Regardless of more severe uterine inflammation found in
      animals from group B, these cows showed the same fertility parameters as healthy
      animals.

PMID- 22883440
TI  - Bilberry ingestion improves disease activity in mild to moderate ulcerative
      colitis - an open pilot study.
AB  - BACKGROUND AND AIMS: A significant fraction of patients with ulcerative colitis
      (UC) is not sufficiently controlled with conventional therapy or suffers from
      therapy related side effects. Anthocyanins, highly abundant in bilberries
      (Vaccinium myrtillus), were shown to have antioxidative and anti-inflammatory
      effects. We aimed to explore the therapeutic potential of bilberries in active
      UC. METHODS: In an open pilot trial with a total follow-up of 9 weeks the effect
      of a daily standardized anthocyanin-rich bilberry preparation was tested in 13
      patients with mild to moderate UC. Clinical, biochemical, endoscopic and
      histologic parameters were assessed. RESULTS: At the end of the 6 week treatment
      interval 63.4% of patients achieved remission, the primary endpoint, while 90.9%
      of patients showed a response. In all patients a decrease in total Mayo score was
      detected (mean: 6.5 and 3.6 at screening and week 7, respectively; p<0.001).
      Fecal calprotectin levels significantly decreased during the treatment phase
      (baseline: mean 778 MUg/g, range 192-1790 MUg/g; end of treatment: mean 305
      MUg/g, range <30-1586 MUg/g; p=0.049), including 4 patients achieving
      undetectable levels at end of treatment. A decrease in endoscopic Mayo score and
      histologic Riley index confirmed the beneficial effect. However, an increase of
      calprotectin levels and disease activity was observed after cessation of bilberry
      intake. No serious adverse events were observed. CONCLUSIONS: This is the first
      report on the promising therapeutic potential of a standardized anthocyanin-rich
      bilberry preparation in UC in humans. These results clearly indicate a
      therapeutic potential of bilberries in UC. Further studies on mechanisms and
      randomized clinical trials are warranted.

PMID- 22883441
TI  - Chicken pox infection in a three months old infant exposed in utero to
      Adalimumab.

PMID- 22883442
TI  - Severe psoriasis preceding diagnosis of large bowel Crohn's disease for 15 years.

PMID- 22883443
TI  - Longitudinal volumetric changes following traumatic brain injury: a tensor-based
      morphometry study.
AB  - After traumatic injury, the brain undergoes a prolonged period of degenerative
      change that is paradoxically accompanied by cognitive recovery. The
      spatiotemporal pattern of atrophy and the specific relationships of atrophy to
      cognitive changes are ill understood. The present study used tensor-based
      morphometry and neuropsychological testing to examine brain volume loss in 17
      traumatic brain injury (TBI) patients and 13 controls over a 4-year period.
      Patients were scanned at 2 months, 1 year, and 4 years post-injury. High
      dimensional warping procedures were used to create change maps of each subject's
      brain for each of the two intervals. TBI patients experienced volume loss in both
      cortical areas and white matter regions during the first interval. We also
      observed continuing volume loss in extensive regions of white matter during the
      second interval. Neuropsychological correlations indicated that cognitive tasks
      were associated with subsequent volume loss in task-relevant regions. The
      extensive volume loss in brain white matter observed well beyond the first year
      post-injury suggests that the injured brain remains malleable for an extended
      period, and the neuropsychological relationships suggest that this volume loss
      may be associated with subtle cognitive improvements.

PMID- 22883444
TI  - Disparities in provision of transplant education by profit status of the dialysis
      center.
AB  - Kidney transplant education is associated with higher transplantation rates;
      however national policies regarding optimal timing and content of transplant
      education are lacking. We aimed to characterize nephrologists' attitudes
      regarding kidney transplant education, and to compare practices between
      nephrologists at for-profit and nonprofit centers. We surveyed 906 nephrologist
      practicing in the United States. Most respondents (81%) felt the ideal time to
      spend on transplant education was >20 min, but only 43% reported actually doing
      so. Spending >20 min was associated with covering more topics, having one-on-one
      and repeated conversations, involving families in discussions and initiating
      discussions at CKD-stage 4. Providers at for-profit centers were significantly
      less likely to spend >20 min (RR = 0.89, 95%CI: 0.80-0.99) or involve families
      (RR = 0.57, 95%CI: 0.38-0.87); they reported that fewer of their patients
      received transplant counseling (RR = 0.58, 95%CI: 0.37-0.96), initiated
      transplant discussions (RR = 0.58, 95%CI: 0.38-0.88), or were eligible for
      transplantation (RR = 0.45, 95%CI: 0.30-0.68). Of nephrologists who spent <=20
      min, those at for-profit centers more often cited lack of reimbursement as a
      reason (30.0% vs. 18.9%, p = 0.02). Disparities in quality of education at for
      profit centers might partially explain previously documented disparities in
      access to transplantation for patients at these centers. National policies
      detailing the optimal timing and content of transplant education are needed to
      improve equity.

PMID- 22883445
TI  - Effect of epidural magnesium on the incidence of chronic postoperative pain after
      video-assisted thoracic surgery.
AB  - OBJECTIVE: The aim of this study was to determine whether the epidural
      administration of magnesium during the perioperative period decreased the
      incidence of chronic postoperative pain (CPOP) at 3 months after video-assisted
      thoracic surgery. DESIGN: Prospective, randomized, and blinded. SETTING: A
      university hospital. PARTICIPANTS: Patients. INTERVENTIONS: Before the induction
      of anesthesia, the patients were assigned randomly to receive normal saline, 5
      mL, (group C, n = 72) or magnesium sulfate, 100 mg (group M, n = 72), epidurally.
      At the end of surgery, group C received a continuous infusion of a mixture of
      0.2% ropivacaine, 226 mL, and fentanyl, 1,200 MUg, through a patient-controlled
      epidural analgesia pump for 48 hours. In group M, magnesium sulfate, 500 mg, was
      added to the infusion. MEASUREMENTS AND MAIN RESULTS: The incidence and severity
      of CPOP were assessed by a telephone survey 3 months after surgery. Patients were
      asked whether they experienced pain and to rank the severity of the pain using a
      3-point scale (1, mild; 2, moderate; 3, severe). The incidences of CPOP were
      42.4% in group C and 49.1% in group M. The severities of pain in the patients
      with CPOP were 1.0 (1-2) in group C and 1.0 (1-2) in group M. The incidence and
      severity of CPOP did not differ between the 2 groups. CONCLUSIONS: The epidural
      administration of magnesium from before the induction of anesthesia to 48 hours
      postoperatively did not decrease significantly the incidence or severity of CPOP
      in patients undergoing video-assisted thoracic surgery.

PMID- 22883446
TI  - CASE 8--2012 intraoperative embolization of renal cell tumor thrombus during
      radical nephrectomy.

PMID- 22883447
TI  - Development and validation of a cerebral oximeter capable of absolute accuracy.
AB  - OBJECTIVE: Cerebral oximetry may be a valuable monitor, but few validation data
      are available, and most report the change from baseline rather than absolute
      accuracy, which may be affected by individuals whose oximetric values are outside
      the expected range. The authors sought to develop and validate a cerebral
      oximeter capable of absolute accuracy. DESIGN: An in vivo research study.
      SETTING: A university human physiology laboratory. PARTICIPANTS: Healthy human
      volunteers were enrolled in calibration and validation studies of 2 cerebral
      oximetric sensors, the Nonin 8000CA and 8004CA. The 8000CA validation study
      identified 5 individuals with atypical cerebral oxygenation values; their data
      were used to design the 8004CA sensor, which subsequently underwent calibration
      and validation. INTERVENTIONS: Volunteers were taken through a stepwise hypoxia
      protocol to a minimum saturation of peripheral oxygen. Arteriovenous saturation
      (70% jugular bulb venous saturation and 30% arterial saturation) at 6 hypoxic
      plateaus was used as the reference value for the cerebral oximeter. Absolute
      accuracy was defined using a combination of the bias and precision of the paired
      saturations (A(RMS)). MEASUREMENTS AND MAIN RESULTS: In the validation study for
      the 8000CA sensor (n = 9, 106 plateaus), relative accuracy was an A(RMS) of 2.7,
      with an absolute accuracy of 8.1, meeting the criteria for a relative (trend)
      monitor, but not an absolute monitor. In the validation study for the 8004CA
      sensor (n = 11, 119 plateaus), the A(RMS) of the 8004CA was 4.1, meeting the
      prespecified success criterion of <5.0. CONCLUSIONS: The Nonin cerebral oximeter
      using the 8004CA sensor can provide absolute data on regional cerebral saturation
      compared with arteriovenous saturation, even in subjects previously shown to have
      values outside the normal population distribution curves.

PMID- 22883448
TI  - A combined deuterium NMR and quantum chemical investigation of inequivalent
      hydrogen bonds in organic solids.
AB  - Deuterium magic angle spinning (MAS) NMR spectroscopy and quantum chemical
      calculations are used to investigate organic solids in which inequivalent
      hydrogen bonds are present. The use of (2)H MAS allows one to measure the
      chemical shift, delta, quadrupolar coupling constant, C(Q), and asymmetry in the
      quadrupolar interaction, eta(Q), for each type of hydrogen bond present in the
      system. Quantum chemical calculations of the magnetic shielding (sigma, which can
      be related to delta) and the electric field gradient (EFG, which can be related
      to C(Q)) are compared to the experimental results and are discussed with respect
      to the relative strengths of the hydrogen bonds within each system.

PMID- 22883449
TI  - [Present status and controversy of treatment for thymoma].

PMID- 22883450
TI  - [Inhibitory effect of folic acid/polyamide-amine as a miR-7 vector on the growth
      of glioma in mice].
AB  - OBJECTIVE: To explore if folic acid/polyamide-amine (FA/PAMAM) enhances the
      therapeutic effect of miR-7gene therapy for glioma in vivo. METHODS: The miR-7
      gene was transfected into U251 glioma cells by FA/PAMAM. The efficiency of gene
      transfection was assessed by fluorescence microscopy. The miR-7 level was detect
      by quantitative RT-PCR. Intracranial glioma models were established in
      thymectomized mice, and FA/PAMAM nanoparticles were transplanted into the tumors
      in situ 3 days later. The animal survival was recorded and the gross tumor volume
      and degree of edema were observed by MRI. Apoptosis in the glioma cells and
      expression of proliferating cell nuclear antigen (PCNA), matrix
      metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed by
      immunohistochemistry, and EGFR and AKT-2 protein expression was detected by
      Western blot assay. RESULTS: Compared with the liposomes, the FA/PAMAM
      nanoparticles were more efficient to transfer miR-7 gene into U251 glioma cells,
      MRI showed that the tumor growth was much slower in the FA/PAMAM/miR-7 group, and
      the animal survival time was longer. The apoptosis rate was (5.3 +/- 0.9)% in the
      control group, (11.4 +/- 2.4)% in the liposome/miR-7 group, and (17.7 +/- 3.7)%
      in the FA/PAMAM/miR-7 group. The immunohistochemical assay showed that the levels
      of PCNA, MMP-2 and MMP-9 protein in the FA/PAMAM/miR-7 group were (34.6 +/-
      5.4)%, (24.5 +/- 4.1)%, (25.4 +/- 5.1)%, respectively, significantly lower than
      those in the liposome/miR-7 group (49.3 +/- 5.9)%, (31.7 +/- 7.1)% and (39.4 +/-
      6.4)%, respectively, and those in the control group (57.3 +/- 7.4)%, (45.4 +/-
      6.9)% and (55.1 +/- 7.3)%, respectively (all P < 0.05). The expressions of EGFR
      and AKT-2 proteins were 1.09 +/- 0.12 and 0.62 +/- 0.10 in the control group,
      0.63 +/- 0.11 and 0.43 +/- 0.07 in the liposome/miR-7 group, and significantly
      deceased (0.47 +/- 0.09 and 0.31 +/- 0.04, respectively) in the FA/PAMAM/miR-7
      group (all P < 0.05). CONCLUSION: Compared with the liposomes, FA/PAMAM can
      transfect miR-7 into glioma cells with a higher efficiency in vivo, makes a
      longer time of the drug action, and shows a certain inhibitory effect on the
      growth of glioma, therefore, might become a new drug targeting agent in gene
      therapy forglioma.

PMID- 22883451
TI  - [Intravesical anchoring of streptavidin-tagged interleukin-4 fusion protein for
      immunotherapy of mouse superficial bladder cancer].
AB  - OBJECTIVE: To evaluate the antitumor efficacy of streptavidin-tagged interleukin
      4 (IL-4-SA) bifunctional fusion protein in the immunotherapy of mouse model of
      superficial bladder cancer. METHODS: IL-4-SA fusion protein was prepared and its
      biological activity was determined. One day after MB49 cell implantation, 100 ul
      of 1 mg/ml NHS-PEO4-biotin was instilled into the bladder for 30 minutes,
      followed by intravesical instillation of 100 ul PBS, GFP-SA+IL-4 or IL-4-SA and
      incubation for 1 hour. The bladder irrigation was performed twice a week for
      three weeks. The CTL cytotoxicity and profile of CD8(+) tumor-infiltrating
      lymphocytes were analyzed. RESULTS: The IL-4-SA fusion protein was durably
      anchored to the biotinylated mucosal surface of bladder wall for up to 5 days.On
      day 80 after the implantation of MB49 cells, all of PBS-treated mice died, and 8
      out of 10 mice in the GFP-SA-treated group died from tumor burden.In contrast, 5
      out of 10 mice in the IL-4-SA-treated group were tumor-free. The MB49 tumor
      specific cytotoxicity from mice in the IL-4-SA group was (11.3 +/- 1.2)%, (22.7
      +/- 1.5)% and (31.0 +/- 3.0)% at the effector to target ratios of 1:1, 25:1 and
      50:1, respectively. But the corresponding cytotoxicity was (4.3 +/- 0.6)%, (9.0
      +/- 1.0)% and (14.3 +/- 1.5)% in the GFP-SA+IL-4 group, and (3.3 +/- 0.6)%, (7.3
      +/- 0.6)%, (12.7 +/- 2.1)% in the PBS group. The tumor-specific cytotoxicity in
      the SA-CD40L group was significantly higher than that in the control groups (P <
      0.05). The infiltrating CD8(+) T cells in tumors in the IL-4-SA-treated group
      were increased compare with those in other groups. CONCLUSION: Intravesical
      anchoring of IL-4-SA elicites strong and long-lasting immunoprotection against
      superficial bladder cancer, and the novel immunotherapy may be an attractive
      therapeutic alternative in future.

PMID- 22883452
TI  - [Anti-tumor effect of cisplatin combined with DC vaccine on tumor-bearing mice].
AB  - OBJECTIVE: To explore the anti-tumor mechanism of the combination of cisplatin
      with DC vaccine in tumor-bearing mice. METHODS: B16 melanoma cells were treated
      with cisplatin at the final concentration of 20 ug/ml in vitro for 24 h. The
      expression of HMGB1, Hsp70 and TGF-beta were detected by Western blot. B16 tumor
      bearing mouse models were generated. The therapeutic effect of the combination of
      cisplatin (100 ug/mouse i.p., for sequential 3 days) and intratumoral injection
      of DC cells (3*10(6)/mouse, twice with a 7-day interval) in the tumor-bearing
      mouse models was evaluated. Expression of MHC II, ICAM-1 and CD86 was analyzed by
      flow cytometry. The mice were sacrificed at 28 days after tumor cell inoculation.
      The tumors were removed and weighed, and tissue samples were taken for
      pathological examination. Tumor infiltrating lymphocytes (TIL) were isolated by
      discontinuous gradient centrifugation. The distribution of T-reg and CD8(+) T
      cells in the TIL was analyzed by flow cytometry, and the ratio of CD8(+) T/T-reg
      was determined. The activity of cytotoxic lymphocytes (CTL) was determined by
      microcytotoxicity assay. RESULTS: Cisplatin enhanced both the B16 cell apoptosis
      and HMGB1 expression. After loading with cisplatin-treated cell lysate, the
      expression of MHC II, ICAM-1 and CD86 on DC cells were (47.5 +/- 8.8)%, (35.5 +/-
      8.3)% and (36.2 +/- 9.2)%, respectively. At 28 days after tumor cell inoculation,
      the tumor weight of the control group was (2.1 +/- 0.6) g, that of the cisplatin
      group was (0.3 +/- 0.2) g and that of cisplatin + DC vaccine group was (0.5 +/-
      0.2) g, showing a significant inhibition of tumor growth (P < 0.01). Furthermore,
      the CD8(+) T/T-reg ratio and CTL activity in TIL were also significantly enhanced
      in the tumor-bearing mice treated with cisplatin + DC vaccine. When the effector
      to-target ratio was 20:1, 10:1 and 5:1, the CTL activity in the cisplatin + DC
      vaccine treated mice was (25.0 +/- 5.0)%, (22.0 +/- 6.0)% and (14.0 +/- 4.0)%,
      respectively, significantly higher than (8.2 +/- 3.6)%, (6.7 +/- 1.8)% and (3.6
      +/- 1.9)%, respectively, in the control group (all P < 0.01). CONCLUSION:
      Cisplatin promotes the anti-tumor effect of DC vaccine by down-regulating T-reg
      cells and enhancing the CTL activity in tumors.

PMID- 22883453
TI  - [Association between single nucleotide polymorphisms of BARD 1 gene and
      susceptibility of early-onset breast cancer in Uygur women in Xinjiang].
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphisms
      (SNPs) of BARD1 gene and susceptibility of early-onset breast cancer in Uygur
      women in Xinjiang. METHODS: A case-control study was designed to explore the
      genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene,
      detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay, in 144
      early-onset breast cancer cases of Uygur women (<= 40 years) and 136 cancer-free
      controls matched by age and ethnicity. The association between SNPs of BARD1 gene
      and risk of early-onset breast cancer in Uygur women was analyzed by
      unconditional logistic regression model. RESULTS: Early age at menarche, late age
      at first pregnancy, and positive family history of cancer may be important risk
      factors of early-onset breast cancer in Uygur women in Xinjiang. The frequencies
      of genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene
      showed significant differences between the cancer cases and cancer-free controls
      (P < 0.05). Compared with wild-type genotype Pro24Ser CC, it showed a lower
      incidence of early-onset breast cancer in Uygur women with variant genotypes of
      Pro24Ser TT (OR = 0.117, 95%CI = 0.058 - 0.236), and dominance-genotype CT+TT (OR
      = 0.279, 95%CI = 0.157 - 0.494), or Arg378Ser CC (OR = 0.348, 95%CI = 0.145 -
      0.834) and Val507Met AA(OR = 0.359, 95%CI = 0.167 - 0.774). Furthermore, SNPS in
      three polymorphisms would have synergistic effects on the risk of breast cancer.
      In addition, the SNP-SNP interactions of dominance-genotypes (CT+TT, GC+CC and
      GA+AA) showed a 52.1% lower incidence of early-onset breast cancer in Uygur women
      (OR = 0.479, 95%CI = 0.230 - 0.995). Stratified analysis indicated that the
      protective effect of carrying T variant genotype (CT/TT) in Pro24Ser and carrying
      C variant genotype (GC/CC) in Arg378Ser were more evident in subjects with early
      age at menarche and negative family history of cancer. With an older menarche
      age, the protective effect was weaker. CONCLUSIONS: SNPs of Pro24Ser(C/T),
      Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene are associated with
      significantly decreased risk of early-onset breast cancer in Uygur women in
      Xinjiang. Early age at menarche and negative family history of cancer can enhance
      the protective effect of mutant allele.

PMID- 22883454
TI  - [Expression of hypoxia inducible factor-1alpha and insulin in pancreatic cancer
      and their correlation].
AB  - OBJECTIVE: To explore the correlation between the expressions of hypoxia
      inducible factor-1alpha (HIF-1alpha) and insulin in pancreatic cancer. METHODS:
      HIF-1alpha and insulin expression was detected by immunohistochemistry in the
      center and the edge of pancreatic adenocarcinoma specimens of 65 cases. Western
      blot was used to detect HIF-1alpha expression and insulin level in the center and
      the edge of pancreatic adenocarcinoma specimens of 28 cases. The relationship
      between HIF-1alpha expression and insulin level in the pancreatic cancer was
      analyzed. RESULTS: The results of immunohistochemistry and Western blot showed
      that HIF-1alpha protein expression was high in both the center and the edge of
      pancreatic cancers (P > 0.05), and insulin level was significantly higher at the
      edge of specimen than that in the center (P < 0.05). HIF-1alpha protein and
      insulin levels were positively correlated at the edge of cancer tissue (r =
      0.374, P < 0.05), but no significant correlation between them in the center of
      cancerous tissue (r = -0.145, P > 0.05). CONCLUSION: Insulin may promote the
      local invasion and metastasis of pancreatic cancer by up-regulating HIF-1alpha.

PMID- 22883455
TI  - [Expression and clinical values of HPV L1 and p16INK4a protein in uterine
      cervical lesions].
AB  - OBJECTIVE: To analyze the expression and clinical values of HPV L1 capsid protein
      and p16INK4a protein in uterine cervical lesions. METHODS: Fifty-four cervical
      intraepithelial neoplasias CIN1, 44 CIN2, 78 CIN3, and 48 squamous cell carcinoma
      were included in this study. All CIN and squamous carcinomas were stained with
      anti-HPV L1 capsid protein antibodies and anti-p16INK4a antibody. Forty-five CIN1
      patients were followed up for 6 years. RESULTS: Forty-five CIN1 patients were
      followed up for 6 years, among them 6 cases showed a progression (One case
      changed to CIN3, 5 cases to CIN2). L1 positivity was found in 50 cases which
      decreased with CIN increasing (chi(2) = 259.923, P < 0.001) while p16INK4a
      positivity was found in 177 cases which co-increased with CIN (chi(2) = 48.842, P
      < 0.001). L1(-)p16INK4a (-) or L1(+)p16INK4a(-) appeared mainly in CIN1 while L1(
      )p16INK4a(+) appeared mainly in CIN2 lesions. No progression was found in the
      group of L1(-)p16INK4a(-) CIN1 patients. The risk of CIN1 progression in L1(
      )p16INK4a(+) group was 66.7% while L1(+)p16INK4a(-) group was 9.5%, and
      L1(+)p16INK4a(+) group was 33.3%. CONCLUSIONS: The expression of p16INK4a
      together with HPV L1 are different in various cervical lesions, and the combined
      detection of p16INK4a and HPV L1 can be helpful for estimating the biological
      potentiality of CIN lesions.

PMID- 22883456
TI  - [Serial (18)F-FDG PET-CT imaging during radiotherapy for nasopharyngeal
      carcinoma: a prospective clinical study].
AB  - OBJECTIVE: The primary aim of this prospective study was to use serial (18)F-FDG
      PET-CT imaging to evaluate the trend of the tumor's maximum standardized uptake
      value (SUVmax) during radiotherapy (RT) for patients with nasopharyngeal
      carcinoma (NPC), and to explore the possibility of early evaluation of the tumor
      bio-metabolic response during radiotherapy. METHODS: Sixty patients with biopsy
      proven primary NPC were prospectively enrolled into the study. All patients
      underwent four (18)F-FDG PET-CT scans: one initial scan before RT/cisplatin based
      concurrent chemoradiotherapy, at the point of 50 Gy during RT, the end of RT, and
      one month after RT, respectively. Tumor (18)F-FDG uptake was analyzed according
      to the World Health Organization pathological type. RESULTS: There was a
      significant difference (P < 0.001) of the mean of SUVmax of the primary site
      among pretreatment (11.20 +/- 5.37) and posttreatment at the dose of 50 Gy (3.50
      +/- 1.59), at the end of RT (3.05 +/- 1.56) and one month after RT (2.52 +/-
      1.46). There was also a significant difference (P < 0.001) of the mean of SUVmax
      of neck node site. However, there was a significant difference of the SUVmax
      between histological WHO type IIb and type IIa in the primary site (P = 0.046)
      [(67 +/- 19)% reduction at dose 50 Gy for type IIb vs. (55 +/- 24)% for type IIa]
      but not in the lymph nodes. CONCLUSIONS: Early PET scan during or right after RT
      instead of conventional 3 months interval after RT is indicated to evaluate the
      tumor response and to develop individualized adaptive radiotherapy in NPC. Our
      next study will attempt to demonstrate the results based on long-term follow-up
      data.

PMID- 22883457
TI  - [Impact of breast density on computer-aided detection (CAD) of breast cancer].
AB  - OBJECTIVE: To evaluate the impact of breast density on computer-aided detection
      (CAD) for breast cancer and the CAD false-positive rate of normal controls.
      METHODS: Two hundred and seventy-one histologically proven breast malignant
      lesions (from Feb. 2008 to Dec. 2009) and 238 randomly selected normal cases were
      classified by mammographic density according to the American College of Radiology
      breast imaging reporting and data system (BI-RADS). Mammograms of BI-RADS 1 or BI
      RADS 2 density were categorized as non-dense breasts, and those of BI-RADS 3 or
      BI-RADS 4 density were categorized as dense breasts. Full-field digital
      mammography (GEMS Senographe) were performed in all patients and controls with
      craniocaudal (CC) and mediolateral oblique (MLO) views. Then the image data were
      transferred to review workstation (SenoAdvantage), and the lesions were marked by
      Second Look Digital CAD system (version 7.2, iCAD). The differences of
      sensitivity and false-positive rate between dense and non-dense breasts were
      compared. RESULTS: Overall, the sensitivity of CAD in detection of cancers was
      84.1% (228/271), there was a statistically significant difference in CAD of
      cancers in dense versus non-dense breasts (P = 0.015). The sensitivity of CAD in
      detection of mass cancers was 76.5% (186/243), in detection of calcification
      cancers was 79.1% (125/158), there was no statistically significant difference in
      CAD performance for the detection of mass cancers versus calcification cancers (P
      = 0.547). There was a significant difference in the CAD performance for the
      detection of mass cancer cases in non-dense versus dense breasts (P = 0.001), but
      no significant difference in the CAD for the detection of calcification cancers
      in non-dense versus dense breasts (P = 0.216). In the controls, the distribution
      of mass false-positive marks did not differ significantly between non-dense and
      dense breast tissue cases (P = 0.207), but the distribution of calcification
      false-positive marks differed significantly between non-dense and dense breast
      tissue cases (P = 0.001). There was a statistically significant difference of
      false-positive marks in non-dense versus dense breasts (P = 0.043). CONCLUSIONS:
      The sensitivity of CAD in the detection of breast cancers is impacted by breast
      density. There is a statistically significant difference in the CAD performance
      for the detection of cancer cases in non-dense versus dense breasts. The false
      positive rate of CAD is lower in dense versus non-dense breasts. It appears
      difficult for CAD in the early detection of breast cancer in the absence of
      microcalcifications, particularly in dense breasts.

PMID- 22883458
TI  - [Value of dual-time-point (18)F-fluorodeoxyglucose integrated positron emission
      and computed tomography in differentiation of malignant from benign
      gastrointestinal diseases].
AB  - OBJECTIVE: To explore the value of dual-time-point (18)F-fluorodeoxyglucose
      integrated positron emission and computed tomography ((18)F-FDG PET-CT) in
      differentiation of malignant from benign gastrointestinal diseases. METHODS:
      Sixty five patients with suspected gastrointestinal lesions underwent dual-time
      point (18)F-FDG PET-CT imaging. Standardized uptake value (SUV) was calculated
      for semi-quantitative assessment. The SUV of the two acquisitions were signed
      SUV(early) and SUV(delayed), respectively. Then the change of SUVmax
      (DeltaSUVmax) was calculated. The ROC curves of the SUV(early), SUV(delayed) and
      DeltaSUV were drawn to find the best cut-off point value for differential
      diagnosis, and then the sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy were calculated, respectively. RESULTS: Of
      the malignant lesions, the SUVmax in delayed imaging were significantly higher
      than those in early imaging, while there were no significant differences of
      SUVmax between the two images of the benign lesions. The DeltaSUVmax of the
      malignant lesions were significantly higher than that of the benign ones. Taking
      the SUVmax higher than 9.2 in early imaging as positive diagnostic criteria, the
      sensitivity was 72.7%, the specificity was 85.7%, the positive predictive value
      was 91.4%, the negative predictive value was 60.0%, and the accuracy was 76.9%.
      Taking the SUVmax higher than 10.9 in delayed imaging as positive diagnostic
      criteria, the sensitivity was 75.0%, the specificity was 90.5%, the positive
      predictive value was 94.3%, the negative predictive value was 63.3%, and the
      accuracy was 80.0%. Taking the DeltaSUVmax higher than 5.1% as positive
      diagnostic criteria, the sensitivity was 95.5%, the specificity was 85.7%, the
      positive predictive value was 93.3%, the negative predictive value was 90.0%, and
      the accuracy was 92.3%. The accuracy of dual-time-point (18)F-FDG PET-CT imaging
      was significantly higher than that of single-time point (18)F-FDG PET-CT imaging.
      CONCLUSION: Dual-time-point (18)F-FDG PET-CT imaging is a useful method for
      differentiating malignant from benign gastrointestinal diseases, and it is
      superior to the single-time point (18)F-FDG PET-CT imaging.

PMID- 22883459
TI  - [Expression and significance of matrix metalloproteinase and tissue inhibitor of
      matrix metalloproteinase in non-melanoma skin cancer].
AB  - OBJECTIVE: To investigate the expression and significance of matrix
      metalloproteinases (MMP-2, MMP-9) and tissue inhibitor of matrix
      metalloproteinase (TIMP-2, TIMP-1) in non-melanoma skin cancer (NMSC). METHODS:
      Thirty six patients with squamous cell carcinoma (SCC) and 32 patients with basal
      cell carcinoma (BCC), confirmed by pathology, were selected, and 30 cases of
      normal skin were selected as control. The expression of MMP-2, MMP-9, TIMP-1 and
      TIMP-2 in all samples were examined by immunohistochemistry and reverse
      transcription polymerase chain reaction (RT-PCR). The expression rate, expression
      intensity and expression level of each factor were recorded. The results were
      compared between the groups. RESULTS: The expression rates of MMP-2 and MMP-9 in
      the control group were 30.0% and 36.7%, the expression levels of MMP-2 and MMP-9
      in the control group were 57.216 +/- 12.785 and 59.318 +/- 13.262, all
      significantly lower than those in the tumor edge and center of the SCC and BCC
      groups (P < 0.01). The expression rates of TIMP-1 and TIMP-2 in the control group
      were 96.7% and 100%, their expression levels were 121.738 +/- 25.516 and 122.612
      +/- 25.964, all significantly higher than those in the SCC and BCC groups (P <
      0.01). The expression levels of MMP-2 and MMP-9 in the tumor center and edge of
      SCC group were significantly higher than those in the corresponding parts of the
      BCC group, while the expression levels of TIMP-1 and TIMP-2 were significantly
      lower than those in the BCC group (P < 0.01). The expression levels of MMP-2 and
      MMP-9 in the tumor edge of the SCC and BCC groups were significantly higher than
      those in the tumor centers (P < 0.01), while the expression levels of TIMP-1and
      TIMP-2 were significantly lower than those in the tumor centers (P < 0.01).
      CONCLUSION: MMP-2, MMP-9 and TIMP-2, TIMP-1 may play an important role in the
      development, progression, invasion and metastasis of non-melanoma skin cancer.

PMID- 22883460
TI  - [Clinical epidemiological analysis of 3602 cases of primary liver cancer in
      Xinjiang].
AB  - OBJECTIVE: To investigate the clinical epidemiological characteristics and the
      major causes of primary liver cancer (PLC) in Xinjiang region. METHODS: The
      clinical epidemiological information on the first page of case history of 3602
      PLC patients, which were diagnosed in our hospital from January 2002 to December
      2010, were retrospectively reviewed and analyzed. RESULTS: Among the 3602 cases,
      the men/women gender ratio was 3.72:1; The proportion of Han, Uighur, Kazakh, and
      other nationality (Hui, Mongolian, Manchu, Xibo nationality) was 81.95%, 9.30%,
      4.14%, 2.89%, and 1.72%, respectively. The comparative difference between Uighur
      and Han nationalities was significant (P < 0.05). The hepatitis virus detection
      results showed that HBs-Ag was positive in 1680 cases (59.57%), HCV-Ab was
      positive in 229 cases (9.41%). Virus detection was negative in 888 patients
      (24.65%). The hepatitis B virus positive rate in Uygur patients was 36.13% and in
      Kazakh patients was 40.37%, both significantly lower than that in patients of Han
      nationality (63.18%, P < 0.05). CONCLUSIONS: In Xinjiang region, the infection
      rate of hepatitis B virus in Uygur and Kazak people is significantly lower than
      that in Han people. The distribution of gender and age does not differ
      significantly among different nationalities, compared with those in other
      regions. The prevalence of primary liver cancer in Xinjiang region has certain
      regional characteristics and features.

PMID- 22883461
TI  - [Clinical analysis of the recurrence of early stage bulky cervical carcinoma].
AB  - OBJECTIVE: To analyze the clinical characteristics, influencing factors and
      outcome of recurrent patients with early stage bulky cervical carcinoma. METHODS:
      Between January 1(st) 2000 and December 31(st) 2009, 76 patients with stage Ib2
      and IIa2 bulky cervical carcinoma developed recurrence and (or) metastasis. The
      recurrence time, recurrence location, recurrence-related factors, treatment and
      survival were analyzed. RESULTS: The median follow up was 44 months (9-137
      months). The overall recurrence and (or) metastasis rate was 22.6%. The 1-, 1-2,
      3-5 and 5-year recurrence and (or) metastasis rates were 38.2%, 27.6%, 30.3% and
      3.9%, respectively. The 5-year survival rate of local recurrence was 34.5%, that
      of distant metastasis was 23.6%, and that of distant metastasis with synchronous
      pelvic recurrence was 11.1%, (P = 0.555). The 5-year survival rate of patients
      who received surgery plus chemotherapy, radiation plus chemotherapy and
      chemotherapy alone after recurrence and (or) metastasis were 53.3%, 30.7% and
      24.6%, respectively (P = 0.686). Univariate analysis demonstrated that tumor
      recurrence and (or) metastasis in patients of the stage Ib2 and IIa2 bulky
      cervical carcinoma were influenced by the disease stage, pelvic lymph node
      metastasis, deep cervical stromal invasion, lymphovascular tumor thrombus and
      pathological types. Multivariate regression analysis demonstrated that pelvic
      lymph node metastasis, lymphovascular tumor thrombus and pathological types were
      the key factors affecting the recurrence and (or) metastases of the stage Ib2 and
      IIa2 bulky cervical carcinoma. Subgroup analysis showed that pelvic lymph node
      metastasis and stage were the main factors affecting the local recurrence in
      those patients, and the pathological type, vascular tumor thrombus and pelvic
      lymph node metastasis were the main factors affecting the distant metastasis.
      CONCLUSIONS: Recurrence and(or) metastasis of early stage bulky cervical cancer
      are mostly happened within 2 years post operation. Patients with pelvic lymph
      node metastasis have high probability to develop local recurrence and distant
      metastasis. Patients with non-squamous cell carcinoma and lymphovascular tumor
      thrombus are more likely to develop distant metastasis. Neoadjuvant chemotherapy
      does not decrease local recurrence and distant metastasis in patients with stage
      Ib2 and IIa2 bulky cervical carcinoma. Individualized treatment is advised for
      recurrent patients.

PMID- 22883462
TI  - [Clinical features of thymic neuroendocrine carcinoma: analysis of 21 cases].
AB  - OBJECTIVE: To improve the understanding of thymic neuroendocrine carcinoma (TNC)
      by retrospective analysis of the clinical data of 21 cases. METHODS: The clinical
      data of 21 patients with TNC treated in the Peking Union Medical College Hospital
      from 1998 to 2010 were retrospectively analyzed. RESULTS: There were 12 males and
      9 females, with onset age ranging from 13 to 67 years and the mean age of 43
      years. The clinical manifestation was diverse, in which the malaise of chest and
      back accounted for 57.1% (12/21), Cushing's syndrome 33.3% (7/21), multiple
      endocrine neoplasia type 1 accounted for 4.8% (1/21), pharyngeal malaise 4.8%,
      superior vena cava syndrome 4.8% (1/21) and asymptomatic patients accounted for
      4.8% (1/21). Eighteen of them demonstrated metastasis, in which 13 had metastasis
      to lymph nodes and local vascular invasion, 9 to lung or pleura, 5 to bone, 1 to
      liver and 1 was recurred in situ. Twenty of them were treated by surgical
      resection. Eleven of them received radiotherapy and 9 chemotherapy after surgery.
      One patient was too severe to endure surgery, and was a treated by chemotherapy
      only. CONCLUSION: TNC is rare, and its clinical features are complex, with a high
      level of malignancy. The first choice of treatment is resection. Adjuvant
      radiotherapy and/or chemotherapy may be applied in patients with metastasis.

PMID- 22883463
TI  - [Comparative analysis of liver function in HBsAg-/HBcAb+ patients with diffuse
      large B-cell lymphoma treated with CHOP and R-CHOP regimens].
AB  - OBJECTIVE: To analyze the liver function in patients with diffuse large B-cell
      lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to
      hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP
      regimens. METHODS: In this retrospective study, 86 DLBCL patients, who were HBsAg
      /HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical
      Sciences between January 2005 and December 2008. The patients were given at least
      two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti
      HBV treatment, and followed-up for at least 12 months after completion of
      therapy. RESULTS: Forty-seven patients received CHOP-like regimen while 39
      patients received R-CHOP-like regimen. There were no significant differences in
      the degree of liver dysfunction between CHOP group and R-CHOP group after the
      1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with
      R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%,
      P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was
      normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively).
      Meanwhile, there were no significant differences in the degree of liver
      dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th
      month, 7th-9th month and 10th-12th month after completion of therapy (7.7% -
      40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05).
      CONCLUSIONS: The present study reveals a low incidence of liver dysfunction in
      HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may
      indicate a potential low incidence of HBV reactivation in these groups, and
      Rituximab do not increase the rate of liver dysfunction. Therefore, these data
      may not support regularly prophylactic antiviral therapy during chemotherapy, but
      close monitoring of liver function, HBV serum markers and HBV DNA level are
      demanded.

PMID- 22883464
TI  - [Clinical characteristics and diagnosis of pulmonary mucosa-associated lymphoid
      tissue-derived (MALT) lymphoma: a retrospective analysis of 29 cases].
AB  - OBJECTIVE: To study the clinical manifestations and radiological characteristics,
      diagnostic methods and outcomes of pulmonary mucosa-associated lymphoid tissue
      derived(MALT) lymphoma. METHODS: A retrospective review of clinical, radiological
      and follow-up data of 29 pulmonary MALT lymphoma cases at Shanghai Pulmonary
      Hospital affiliated to Tong Ji University from January 2002 to June 2010 was
      performed. RESULTS: Among these patients, there were 19(65.5%) males and 10
      (34.5%) females aged from 27 to 73 (median 53) years old. Common clinical
      manifestations were cough (51.7%), fever (20.7%), apnea (17.2%), chest pain
      (17.2%), fatigue (13.8%) and weight loss (13.8%), while 9(31.0%) cases had no
      symptoms at diagnosis. The characteristics of the chest CT showed that 22 (75.9%)
      of the cases had patch infiltration or consolidation of the lung, 7(24.1%) of the
      cases had mass, and 15 (51.7%) unilateral and 14(48.3%) bilateral lesions. Their
      diagnosis duration varied between 0.5 and 96 months. 18(62.1%) cases were
      confirmed by surgery (15 open lung and 7 video-assisted thoracic surgery, VAST),
      4 (13.8%) by percutaneous lung biopsy, 5 (17.2%) by bronchoscopic biopsy, and 2
      (6.9%) by peripheral lymph node biopsy. The treatment methods included surgery,
      combined chemotherapy, radiotherapy and Chinese herbal medicine. The 1- and 3
      year-survival rates were 92.3% and 87.4%, respectively. CONCLUSIONS: Pulmonary
      MALT lymphoma is atypical in clinical manifestations and radiological
      characteristics, and easy to be misdiagnosed. Local diseases are mainly treated
      by operation while extensive diseases receive combined chemotherapy. A proper
      diagnosis is mainly based on pathological biopsy. Patients with MALT lymphoma
      have a favorable outcome. Poor prognosis may be connected with poor performance
      status and long diagnosis duration.

PMID- 22883465
TI  - [Endobronchial metastases from breast cancer: a clinicopathological and survival
      analysis].
AB  - OBJECTIVE: Endobronchial metastases (EBM) secondary to extrapulmonary solid
      malignant tumors are rare but may occur. The most common extrathoracic
      malignancies associated with EBM are colorectal, renal and breast cancer. This
      study aimed to evaluate the clinicopathological aspects of EBM from breast cancer
      and the prognosis of the patients. METHODS: Clinicopathological data of 11 cases
      diagnosed as EBM from breast cancer treated in our hospital from 2003 to 2010
      were re-evaluated. Their symptoms, recurrence interval, radiological features,
      histopathological properties, and prognosis were assessed. RESULTS: Eleven cases
      were diagnosed by bronchoscopic bronchial biopsy. The median interval from
      diagnosis of breast cancer was 57 months (range: 11 - 189 mo). All patients had
      other proven metastases when the EBM was diagnosed. The most frequently observed
      symptoms were cough (8 cases). Interestingly, two patients were asymptomatic.
      Hilar mass (5 cases) was a common radiological finding. No disaccordance between
      the hormone receptor status in the primary and metastatic lesions in these
      patients was found. The median survival after EBM diagnosis was 21 months (range:
      6 - 36) with four patients still alive and one of these four patients was
      surviving more than 7 years. CONCLUSIONS: On average, EBM is diagnosed about 5
      years after the diagnosis of breast cancer, which is a relatively long lead time,
      but the median survival time is short, as 21 months in our group. The treatment
      plan must be individualized, because in some cases, long-term survival can be
      expected.

PMID- 22883466
TI  - [Current status and perspectives of individualized therapy for non-small cell
      lung cancer based on molecular targeting].

PMID- 22883467
TI  - IsomiRs--the overlooked repertoire in the dynamic microRNAome.
AB  - The development of deep sequencing has enabled the identification of novel
      microRNAs (miRNAs), leading to a growing appreciation for the fact that
      individual miRNAs can be heterogeneous in length and/or sequence. These variants,
      termed isomiRs, can be expressed in a cell-specific manner, and numerous recent
      studies suggest that at least some isomiRs may affect target selection, miRNA
      stability, or loading into the RNA-induced silencing complex (RISC). Reports
      indicating differential functionality for isomiRs are currently confined to
      several specific variants, and although isomiRs are common, their broader
      biological significance is yet to be fully resolved. Here we review the growing
      body of evidence suggesting that isomiRs have functional differences, of which at
      least some appear biologically relevant, and caution researchers to take miRNA
      isoforms into consideration in their experiments.

PMID- 22883468
TI  - Autism in siblings with autosomal dominant nocturnal frontal lobe epilepsy.
AB  - In 1999, Hirose et al. reported a Japanese family with autosomal dominant
      nocturnal frontal lobe epilepsy (ADNFLE) associated with a neuronal nicotinic
      acetylcholine receptor alpha4 subunit mutation (S252L). We followed the siblings
      of this family, and found that the elder brother had Asperger's disorder without
      mental retardation (MR) and the younger brother had autistic disorder with
      profound MR. The clinical epileptic features of the siblings were very similar,
      and both had deficits in socialization, but their cognitive development differed
      markedly. It thus seems that epilepsy is the direct phenotype of the S252L
      mutation, whereas other various factors modulate the cognitive and social
      development. No patients with ADNFLE have previously been reported to have autism
      spectrum disorder or profound MR.

PMID- 22883469
TI  - MicroRNA-133b inhibits the growth of non-small-cell lung cancer by targeting the
      epidermal growth factor receptor.
AB  - Both the deregulation of microRNAs and epidermal growth factor receptor (EGFR)
      are emerging as important factors in non-small-cell lung cancer (NSCLC). Here,
      miR-133b was found to be associated with tumor stage, the extent of regional
      lymph node involvement, stage, visceral pleura or vessel invasion and EGFR mRNA
      expression in Chinese patients with NSCLC. Bioinformatic analysis and luciferase
      reporter assay revealed that miR-133b can interact specifically with the 3'-UTR
      of EGFR mRNA. Functionally, miR-133b transfection showed regulatory activity in
      translationally repressing EGFR mRNA. Moreover, miR-133b transfection may
      modulate apoptosis, invasion and sensitivity to EGFR-TKI through the EGFR
      signaling pathways, especially in EGFR-addicted NSCLC cells. Taken together, our
      findings show that miR-133b can inhibit cell growth of NSCLC through targeting
      EGFR and regulating its downstream signaling pathway. This finding has important
      implications for the development of targeted therapeutics for a number of EGFR
      addicted cancers.

PMID- 22883470
TI  - Incidence, causes, severity and treatment of throat discomfort: a four-region
      online questionnaire survey.
AB  - BACKGROUND: Acute sore throat is commonly associated with viral infections.
      Consumers typically rely on over-the-counter treatments and other remedies to
      treat symptoms; however, limited information is available regarding consumer
      perceptions of sore throat or treatment needs. The aim of this study was to
      investigate perceptions of throat discomfort and how these influence attitudes
      and consumer behaviour with regard to treatment. METHODS: Online consumer surveys
      were completed by participants invited by email between 2003 and 2004 in four
      markets: the UK, France, Poland, and Malaysia. The questionnaire consisted of 24
      questions that covered key issues surrounding throat discomfort including
      incidence in the past 12 months, causes, severity, effects on functionality and
      quality of life, actions taken to relieve throat discomfort, the efficacy of
      these approaches and the reasons behind using specific products. RESULTS: In
      total, 6465 men and women aged >=18 years were surveyed, identifying 3514
      participants who had suffered throat discomfort/irritation in the past 12 months
      (response rate of 54%). These participants completed the full survey. The
      breakdown of throat discomfort sufferers was: UK, 912; France, 899; Poland, 871;
      Malaysia, 832. A high proportion of respondents experienced one or more instances
      of throat discomfort in the previous 12 months, with an overall incidence of 54%.
      Infections including the common cold/influenza and other bacteria/viruses were
      commonly perceived causes of throat discomfort (72% and 46%, respectively).
      Physical and environmental factors were also perceived to be causative, including
      airborne pollution (28%), smoking (23%), and air conditioning (31%). Symptoms
      perceived to be caused by an infection were associated with a higher degree of
      suffering (mean degree of suffering for bacteria/virus and common cold/influenza;
      3.4 and 3.0, respectively). Medicinal products were used for all perceived
      causes, but more commonly for sore throats thought to be caused by infections.
      Cold drinks were used more often for symptoms thought to be due to physical and
      environmental causes. CONCLUSIONS: Not all throat discomfort is the same, as
      demonstrated by the range of perceived causes and the emotional and physical
      symptoms experienced. Patient expectations regarding treatment of throat
      discomfort differs and treatments should be tailored by pharmacists to suit the
      cause.

PMID- 22883471
TI  - Marked eosinophilia in a patient with history of severe atypical Kawasaki
      disease.
AB  - An infant with recent atypical, treatment-refractory Kawasaki disease presented
      with marked eosinophilia. Workup failed to identify an etiology. The eosinophilia
      spontaneously resolved. Eosinophilia has been observed in the acute phase of
      Kawasaki disease, but has not been reported following recovery. 

PMID- 22883472
TI  - Investigation on the photoconductive behaviors of an individual AlN nanowire
      under different excited lights.
AB  - Ultra-long AlN nanowire arrays are prepared by chemical vapor deposition, and
      the photoconductive performances of individual nanowires are investigated in our
      self-built measurement system. Individual ultra-long AlN nanowire (UAN) exhibits
      a clear photoconductive effect under different excited lights. We attribute the
      positive photocurrent response of individual UAN to the dominant molecular
      sensitization effect. It is found that they have a much faster response speed (a
      rise and decay time of about 1 ms), higher photocurrent response (2.7*106), and
      more reproductive working performance (the photocurrent fluctuation is lower than
      2%) in the air environment. Their better photoconductive performances are
      comparable to many nanostructures, which are suggested to be a candidate for
      building promising photosensitive nanodevices in the future.

PMID- 22883473
TI  - Estimating remission from untreated major depression: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Few studies have examined spontaneous remission from major
      depression. This study investigated the proportion of prevalent cases of
      untreated major depression that will remit without treatment in a year, and
      whether remission rates vary by disorder severity. METHOD: Wait-list controlled
      trials and observational cohort studies published up to 2010 with data describing
      remission from untreated depression at <= 2-year follow-up were identified.
      Remission was defined as rescinded diagnoses or below threshold scores on
      standardized symptom measures. Nineteen studies were included in a regression
      model predicting the probability of 12-month remission from untreated depression,
      using logit transformed remission proportion as the dependent variable.
      Covariates included age, gender, study type and diagnostic measure. RESULTS: Wait
      listed compared to primary-care samples, studies with longer follow-up duration
      and older adult compared to adult samples were associated with lower probability
      of remission. Child and adolescent samples were associated with higher
      probability of remission. Based on adult samples recruited from primary-care
      settings, the model estimated that 23% of prevalent cases of untreated depression
      will remit within 3 months, 32% within 6 months and 53% within 12 months.
      CONCLUSIONS: It is undesirable to expect 100% treatment coverage for depression,
      given many will remit before access to services is feasible. Data were drawn from
      consenting wait-list and primary-care samples, which potentially over-represented
      mild-to-moderate cases of depression. Considering reported rates of spontaneous
      remission, a short untreated period seems defensible for this subpopulation,
      where judged appropriate by the clinician. Conclusions may not apply to
      individuals with more severe depression.

PMID- 22883474
TI  - Service: "sine qua non".

PMID- 22883475
TI  - The Nordic Maintenance Care Program: Maintenance care - what happens during the
      consultation? Observations and patient questionnaires.
AB  - BACKGROUND: Because maintenance care (MC) is frequently used by chiropractors in
      the management of patients with back pain, it is necessary to define the
      rationale, frequency and indications for MC consultations, and the contents of
      such consultations. The objectives of the two studies described in this article
      are: i) to determine the typical spacing between visits for MC patients and to
      compare MC and non-MC patients, ii) to describe the content of the MC
      consultation and to compare MC and non-MC patients and iii) to investigate the
      purposes of the MC program. METHOD: In two studies, chiropractors who accepted
      the MC paradigm were invited to assist with the data collection. In study 1,
      patients seen by seven different chiropractors were observed by two chiropractic
      students. They noted the contents of the observed consultations. In study 2, ten
      chiropractors invited their MC patients to participate in an anonymous survey.
      Participants filled in a one page questionnaire containing questions on their
      view of the purposes and contents of their MC consultations. In addition,
      information was obtained on the duration between appointments in both studies.
      RESULTS: There were 178 valid records in study 1, and in study 2 the number of
      questionnaires received was 373. The time interval between MC visits was close to
      nine weeks and for non-MC consultations it was two weeks.The content of the
      consultations in study 1 was similar for MC and non-MC patients with treatment
      being the most time-consuming element followed by history taking/examination. MC
      consultations were slightly shorter than non-MC consultations.In study 2, the
      most common activities reported to have taken place were history taking and
      manipulative therapy. The most commonly reported purposes were to prevent
      recurring problems, to maintain best possible function and /or to stay as pain
      free as possible. CONCLUSIONS: The results from these two studies indicate that
      MC consultations commonly take place with around two months intervals, and that
      history taking, examination and treatment are as important components in MC as in
      non-MC consultations. Further, the results demonstrate that most patients
      consider the goal to be secondary or tertiary prevention.

PMID- 22883476
TI  - Lateralisation of sound in temporal-lobe epilepsy: comparison between pre- and
      postoperative performances and ERPs.
AB  - OBJECTIVE: Our aim was to investigate if spatial hearing is impaired in mesial
      temporal lobe epilepsy and temporal lobectomy has an effect on this function.
      METHODS: Thirteen patients with mesial temporal lobe epilepsy (TLE) due to
      sclerosis in their left (n=6) or right (n=7) hippocampus were studied. Their
      sound lateralisation performance indexed by d' was tested against that of a group
      of normal subjects (n=13). Patients' ERPs to lateralisation shifts induced by
      interaural disparities of intensity (IID) and time (ITD) were also recorded.
      Eight of the patients were re-tested after they underwent anterior temporal
      lobectomy, which involved the resection/removal of medial structures including
      amygdala, hippocampus and parahippocampal gyrus. RESULTS: The sound
      lateralisation performance of the TLE patients was significantly lower than
      normal subjects, and this disadvantage of the patients was specific to IID-based
      lateralisation. Amplitudes of their N1 and P2 responses to laterally shifting
      sounds were much lower than those reported previously for normal subjects.
      Lobectomy did not have a statistically significant effect on patients' sound
      lateralisation performance nor on the amplitude of their auditory directional
      ERPs. CONCLUSIONS: The results show that especially the IID-based sound
      lateralisation performance is impaired in TLE patients and that lobectomy should
      not cause any further deterioration. SIGNIFICANCE: This study suggests that a
      test for assessing the ability of sound lateralisation based on each of the IID
      and ITD cues should be included in the evaluation of TLE patients.

PMID- 22883477
TI  - Deterioration of horizontal saccades in progressive supranuclear palsy.
AB  - OBJECTIVE: To investigate horizontal saccade changes according to disease stage
      in patients with progressive supranuclear palsy (PSP). METHODS: We studied
      visually and memory guided saccades (VGS and MGS) in 36 PSP patients at various
      disease stages, and compared results with those in 66 Parkinson's disease (PD)
      patients and 58 age-matched normal controls. RESULTS: Both vertical and
      horizontal saccades were affected in PSP patients, usually manifesting as "slow
      saccades" but sometimes as a sequence of small amplitude saccades with relatively
      well preserved velocities. Disease progression caused saccade amplitude reduction
      in PSP but not PD patients. In contrast, VGS and MGS latencies were comparable
      between PSP and PD patients, as were the frequencies of saccades to cue,
      suggesting that voluntary initiation and inhibitory control of saccades are
      similar in both disorders. Hypermetria was rarely observed in PSP patients with
      cerebellar ataxia (PSPc patients). CONCLUSIONS: The progressively reduced
      accuracy of horizontal saccades in PSP suggests a brainstem oculomotor pathology
      that includes the superior colliculus and/or paramedian pontine reticular
      formation. In contrast, the functioning of the oculomotor system above the
      brainstem was similar between PSP and PD patients. SIGNIFICANCE: These findings
      may reflect a brainstem oculomotor pathology.

PMID- 22883478
TI  - An age-related change in the ipsilateral silent period of a small hand muscle.
AB  - OBJECTIVE: To establish the presence or absence of an age effect on the
      ipsilateral silent period (iSP) for the abductor pollicis brevis (APB) muscle in
      healthy subjects. METHODS: Twenty young adults (10 men, 10 women; age range: 20
      40) and 20 older adults (10 men, 10 women; age range: 50-70) were matched by age
      (+30 years), gender and height (+/-5 cm). All were right-handed. We investigated
      the iSP for the APB by applying transcranial magnetic stimulation (TMS) and
      recording surface electromyograms. The contralateral motor-evoked potential (MEP)
      onset latency, the iSP onset and end latency (iSPOL and iSPEL) were measured and
      the iSP duration (iSPD) and transcallosal conduction time (TCT) were calculated.
      We evaluated the correlation between age and iSP, the latter's intra- and
      intersession reproducibility and potential influencing factors. RESULTS: Mean
      iSPOL, iSPEL and TCT values were significantly greater in older adults (both men
      and women) than in young adults. Intra- and intersession reproducibility was
      good. The mean left-side iSPEL and iSPD were longer than the right-side mean
      values in young adults but not in older adults. In both age groups, women
      displayed shorter latencies than men. CONCLUSIONS: There is a strong effect of
      age on iSP parameters. SIGNIFICANCE: Our iSP results may evidence a decrease in
      transcallosal excitability with age, rather than slowing of the transcallosal
      interneuron conduction velocity.

PMID- 22883479
TI  - Morphology and structure of polymer layers protecting dental enamel against
      erosion.
AB  - OBJECTIVES: Human dental erosion caused by acids is a major factor for tooth
      decay. Adding polymers to acidic soft drinks is one important approach to reduce
      human dental erosion caused by acids. The aim of this study was to investigate
      the thickness and the structure of polymer layers adsorbed in vitro on human
      dental enamel from polymer modified citric acid solutions. METHODS: The polymers
      propylene glycol alginate (PGA), highly esterified pectin (HP) and gum arabic
      (GA) were used to prepare polymer modified citric acids solutions (PMCAS, pH
      3.3). With these PMCAS, enamel samples were treated for 30, 60 and 120s
      respectively to deposit polymer layers on the enamel surface. Profilometer
      scratches on the enamel surface were used to estimate the thickness of the
      polymer layers via atomic force microscopy (AFM). The composition of the
      deposited polymer layers was investigated with X-ray photoelectron spectroscopy
      (XPS). In addition the polymer-enamel interaction was investigated with zeta
      potential measurements and scanning electron microscopy (SEM). RESULTS: It has
      been shown that the profilometer scratch depth on the enamel with deposited
      polymers was in the range of 10nm (30s treatment time) up to 25nm (120s treatment
      time). Compared to this, the unmodified CAS-treated surface showed a greater
      scratch depth: from nearly 30nm (30s treatment time) up to 60nm (120s treatment
      time). Based on XPS measurements, scanning electron microscopy (SEM) and zeta
      potential measurements, a model was hypothesized which describes the layer
      deposited on the enamel surface as consisting of two opposing gradients of
      polymer molecules and hydroxyapatite (HA) particles. SIGNIFICANCE: In this study,
      the structure and composition of polymer layers deposited on in vitro dental
      enamel during treatment with polymer modified citric acid solutions were
      investigated. Observations are consistent with a layer consisting of two opposing
      gradients of hydroxyapatite particles and polymer molecules. This leads to
      reduced erosive effects of citric acid solutions on dental enamel surfaces.

PMID- 22883480
TI  - Interfacial nanoleakage and internal cement thickness of three esthetic crown
      systems.
AB  - OBJECTIVES: To evaluate interfacial nanoleakage expression of the combination of
      different cementation procedures and different crown systems. METHODS: Forty-five
      human premolars prepared to receive single crowns were randomly divided into
      three groups (n=15) based on the materials to be used for crown fabrication and
      cementation: group 1: Zirc (Ivoclar-Vivadent) cemented with Multilink Automix;
      group 2: Ivoclar disilicate IPS Empress 2 luted with Excite DSC in combination
      with Variolink II; group 3: AAdva Zirconia (GC) cemented with G-Cem Automix. The
      specimens were then assessed for interfacial nanoleakage expression and the
      amount of silver deposits along the interface was quantified. The thickness of
      the cement was assessed at 5 different levels: cervical margins, midway between
      the cervical margin and the occlusal wall along the axial walls and at the
      occlusal wall. The nanoleakage scores and the cement thickness were analyzed with
      Kruskall-Wallis non-parametric Analysis of Variance and Dunn's Multiple-range
      post hoc test. RESULTS: Group 2 showed significantly less nanoleakage expression
      than group 1 (p<0.05). The groups can be ranked in the following order 3<1<2 with
      regard to the cement thickness. CONCLUSIONS: There was no correlation among
      combination of different cementation procedures and different crown systems and
      interfacial nanoleakage. Also the cement thickness and the degree of nanoleakage
      cannot be related. The amount of cement found at the cervical margins of all
      groups showed discrepancies within a clinical acceptable range.

PMID- 22883481
TI  - Oxidative stress in multiple sclerosis patients in clinical remission:
      association with the expanded disability status scale.
AB  - Increased levels of oxidative stress markers and/or decreased levels of
      antioxidant molecules have been described in patients with multiple sclerosis
      (MS). This imbalance has been implicated in demyelination and axonal damage. The
      aims of this study were to evaluate oxidative stress in MS patients and to verify
      its correlation with disability as assessed by the expanded disability status
      scale (EDSS). This case-controlled study included 91 patients with relapsing
      remitting multiple sclerosis (RR-MS) and 196 healthy individuals matched by age,
      gender, ethnicity, smoking status, and body mass index. Oxidative stress was
      evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH),
      carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping
      antioxidant parameter (TRAP), sulfhydryl groups of proteins and serum uric acid
      levels. MS patients exhibited higher plasma levels of CL-LOOH (p<0.0001) and
      carbonyl protein (p=0.0081), and lower plasma levels of NOx (p<0.0001), TRAP
      (p=0.0088), and sulfhydryl groups (p=0.0003) compared to the control subjects. A
      multivariate analysis showed an association between oxidative markers and the
      presence of MS. Patients with an EDSS >3.5 showed higher CL-LOOH than control
      subjects (p=0.0093). A positive correlation was observed between CL-LOOH and EDSS
      (r=0.3244, p=0.0026) and between carbonyl protein and EDSS (r=0.3012, p=0.0041).
      These results demonstrate that oxidative stress plays an important role in the
      physiopathology of MS progression.

PMID- 22883482
TI  - Dementia is strongly associated with 90-day mortality in lobar cerebral amyloid
      angiopathy related intra-cerebral haemorrhage.
AB  - BACKGROUND: While evidence suggests that lobar intracerebral haemorrhage (ICH) is
      linked with dementia and cognitive impairment, the association between cognition
      and mortality risk from ICH is unclear. AIMS: To examine the association between
      dementia or cognitive impairment and short- and medium-term mortality post ICH.
      METHODS: Patients with primary ICH were classified into lobar and non-lobar ICH
      using radiological criteria. Patients' characteristics and radiological measures
      were collected at the baseline along with history of dementia and cognitive
      impairment. Mortality risks at 7, 30, 60, and 90 days were assessed using
      multiple logistic regression adjusting for potential confounders identified as
      significant associates in univariate models. RESULTS: A total of 136 patients
      (males 50%, mean age 77 years, SD 10) were included in this study. Out of 53
      (39%) patients with lobar ICH 47 (89%) were classified as having possible and 6
      (11%) as probable cerebral amyloid angiopathy (CAA). In lobar ICH the prevalence
      of history of dementia or cognitive impairment, confusion at presentation,
      previous ICH, multiple haemorrhages, and initial haematoma volume were
      significantly higher (p<0.05). In lobar ICH the significant mortality predictors
      (p<0.05) were history of dementia or cognitive impairment (90 days), prior
      antiplatelet use (60 and 90 days), initial haematoma volume (60 days), male sex
      (30 and 60 days), age (30, 60, 90 days), and low Glasgow Coma Scale (GCS) (7 and
      30 days). In non-lobar ICH prior use of anticoagulation, initial haematoma
      volume, low GCS and age were significant mortality predictors (p<0.05).
      CONCLUSION: A history of dementia or cognitive impairment is more common in lobar
      CAA-related ICH and it is a medium-term mortality predictor in lobar ICH but not
      in deep non-lobar ICH.

PMID- 22883483
TI  - Limb-girdle phenotype is frequent in patients with myopathy associated with GNE
      mutations.
AB  - The gene GNE encodes a bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase. Its mutations are found in distal myopathy with rimmed
      vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM). Those disorders
      are characterized clinically by predominant anterior tibial muscle weakness and
      atrophy, and pathologically by rimmed vacuoles on muscle biopsy. We analyzed 11
      Korean patients with GNE mutations. The mutations showed ethnic similarity to
      those of Japanese patients, showing the highest frequency with V572L. Another
      mutation of C13S was also found recurring in our patient group. Interestingly,
      about half of the patients showed limb-girdle myopathy rather than distal
      myopathy. This was further represented by limb muscle CT scans revealing atrophic
      hamstring and relatively spared anterior tibial muscle. However, quadriceps
      muscles were consistently spared both in distal and limb-girdle phenotypes. In
      conclusion, this study demonstrates a phenotypic diversity associated with GNE
      mutations. Recognizing a wider clinical spectrum of GNE mutations will help
      benefit more patients with imminent new therapy.

PMID- 22883484
TI  - Patients with Lynch syndrome mismatch repair gene mutations are at higher risk
      for not only upper tract urothelial cancer but also bladder cancer.
AB  - BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is
      caused by mutations in mismatch repair (MMR) genes. An increased risk for upper
      tract urothelial carcinoma (UTUC) has been described in this population; however,
      data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess
      the risk of BCa in MMR mutation carriers and suggest screening and management
      recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007
      were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for
      321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis
      type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E.
      coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation
      increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using
      the Surveillance Epidemiology and End Results public database, were used to
      compare cancer risk in patients with MMR mutations with the Canadian population.
      Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR
      proteins were also performed and the results compared with matched sporadic
      bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2
      mutations (6.21%, p<0.001 compared with the Canadian population) were found to
      have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of
      these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the
      matched sporadic cases, which all displayed normal expression of MSH2 and MLH1.
      The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors
      were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5
      splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer.
      Limitations include possible inflated risk estimates due to ascertainment bias.
      CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not
      only UTUC but also BCa and could be offered appropriate screening.

PMID- 22883487
TI  - A medical crisis in Syria.

PMID- 22883486
TI  - Prevalence and determinants of the metabolic syndrome among Tunisian adults:
      results of the Transition and Health Impact in North Africa (TAHINA) project.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome (MetS) and its
      components and to evaluate the relationship between this diagnosis and
      cardiovascular risk factors, demographic and socio-economic variables. DESIGN: A
      cross-sectional study using a questionnaire including information on
      sociodemographic and CVD risk factors. Blood pressure, anthropometric indices,
      fasting glucose and lipid profile were measured. MetS was defined according to
      the criteria of the National Cholesterol Education Program, Adult Treatment Panel
      III. SETTING: The whole Tunisian territory; Transition and Health Impact in North
      Africa (TAHINA) project. SUBJECTS: A total of 4654 individuals (1840 men and 2814
      women), aged 35 to 74 years, who participated in the Tunisian national survey.
      RESULTS: The overall prevalence of MetS was 30.0 %, higher in women (36.1 %) than
      in men (20.6 %; P < 0.001). In both genders MetS prevalence increased
      significantly with age (P < 0.001), but this increase was more important in
      women. Multiple regression analyses showed that the odds for MetS increased
      significantly with urban area for both men and women (P < 0.05 and P < 0.001,
      respectively). The multivariate models showed also that the odds for MetS
      increased significantly with increasing level of education and in those with a
      family history of CVD for men (both P < 0.05) and after the menopausal transition
      for women (P < 0.05). CONCLUSIONS: The study highlights the MetS problem in a
      middle-income developing country. There is an urgent need for a comprehensive,
      integrated, population-based intervention programme to ameliorate the growing
      problem of MetS in Tunisians.

PMID- 22883485
TI  - Total protein, albumin and low-molecular-weight protein excretion in HIV-positive
      patients.
AB  - BACKGROUND: Chronic kidney disease is common in HIV positive patients and renal
      tubular dysfunction has been reported in those receiving combination
      antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to
      severe renal tubular disease as well as proximal tubular dysfunction. Markedly
      elevated urinary concentrations of retinal-binding protein (RBP) have been
      reported in patients with severe renal tubular disease, and low-molecular-weight
      proteins (LMWP) such as RBP may be useful in clinical practice to assess renal
      tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein
      and albumin in the urine of a sample of HIV positive patients. METHODS: In a
      cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil
      gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of
      317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR
      and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART
      containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI)
      or TFV and a protease-inhibitor (TFV/PI). RESULTS: Proteinuria was present in
      10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for
      approximately 10 % of total urinary protein. RBPCR was within the reference range
      in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall
      differences in urine protein, albumin, and LMWP levels were observed among
      patients stratified by cART exposure, although a greater proportion of patients
      exposed to TFV/PI had RBPCR >38.8 MUg/mmol (343 MUg/g) (p = 0.003). In
      multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75
      mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with
      upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to
      NGALCR, PCR or ACR. CONCLUSIONS: In HIV positive patients, proteinuria was
      predominantly of tubular origin and microalbuminuria was common. RBPCR in
      patients without overt renal tubular disease was generally within the reference
      range, including those receiving TFV. RBP therefore appears a promising biomarker
      for monitoring renal tubular function in patients receiving TFV and for
      distinguishing patients with normal tubular function or mild tubular dysfunction
      from those with severe renal tubular disease or Fanconi syndrome.

PMID- 22883488
TI  - Preventing hypertension: a hopeless dream?

PMID- 22883489
TI  - Psychological maltreatment of children: everyone's problem.

PMID- 22883490
TI  - Hypertension: treatments, diabetes, and developing regions.

PMID- 22883491
TI  - Balancing the cardiometabolic benefits and risks of statins.

PMID- 22883494
TI  - Ernesto Schiffrin: essential player in hypertension.

PMID- 22883495
TI  - Paul Ridker: reaching the end game.

PMID- 22883496
TI  - New global estimates of malaria deaths.

PMID- 22883497
TI  - New global estimates of malaria deaths.

PMID- 22883498
TI  - New global estimates of malaria deaths.

PMID- 22883499
TI  - New global estimates of malaria deaths.

PMID- 22883500
TI  - Internet-based CBT for adolescents with chronic fatigue syndrome.

PMID- 22883501
TI  - Internet-based CBT for adolescents with chronic fatigue syndrome.

PMID- 22883503
TI  - European licensing of maintenance treatment in schizophrenia.

PMID- 22883504
TI  - Assessment of interventions to address the built environment.

PMID- 22883505
TI  - Engaging with leadership learning in the workplace.

PMID- 22883506
TI  - Putting respect to work.

PMID- 22883507
TI  - Cardiovascular benefits and diabetes risks of statin therapy in primary
      prevention: an analysis from the JUPITER trial.
AB  - BACKGROUND: In view of evidence that statin therapy increases risk of diabetes,
      the balance of benefit and risk of these drugs in primary prevention has become
      controversial. We undertook an analysis of participants from the JUPITER trial to
      address the balance of vascular benefits and diabetes hazard of statin use.
      METHODS: In the randomised, double-blind JUPITER trial, 17,603 men and women
      without previous cardiovascular disease or diabetes were randomly assigned to
      rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary
      endpoint (myocardial infarction, stroke, admission to hospital for unstable
      angina, arterial revascularisation, or cardiovascular death) and the protocol
      prespecified secondary endpoints of venous thromboembolism, all-cause mortality,
      and incident physician-reported diabetes. In this analysis, participants were
      stratified on the basis of having none or at least one of four major risk factors
      for developing diabetes: metabolic syndrome, impaired fasting glucose, body-mass
      index 30 kg/m(2) or higher, or glycated haemoglobin A(1c) greater than 6%. The
      trial is registered at ClinicalTrials.gov, NCT00239681. FINDINGS: Trial
      participants with one or more major diabetes risk factor (n=11,508) were at
      higher risk of developing diabetes than were those without a major risk factor
      (n=6095). In individuals with one or more risk factors, statin allocation was
      associated with a 39% reduction in the primary endpoint (hazard ratio [HR] 0.61,
      95% CI 0.47-0.79, p=0.0001), a 36% reduction in venous thromboembolism (0.64,
      0.39-1.06, p=0.08), a 17% reduction in total mortality (0.83, 0.64-1.07, p=0.15),
      and a 28% increase in diabetes (1.28, 1.07-1.54, p=0.01). Thus, for those with
      diabetes risk factors, a total of 134 vascular events or deaths were avoided for
      every 54 new cases of diabetes diagnosed. For trial participants with no major
      diabetes risk factors, statin allocation was associated with a 52% reduction in
      the primary endpoint (HR 0.48, 95% CI 0.33-0.68, p=0.0001), a 53% reduction in
      venous thromboembolism (0.47, 0.21-1.03, p=0.05), a 22% reduction in total
      mortality (0.78, 0.59-1.03, p=0.08), and no increase in diabetes (0.99, 0.45
      2.21, p=0.99). For such individuals, a total of 86 vascular events or deaths were
      avoided with no new cases of diabetes diagnosed. In analysis limited to the 486
      participants who developed diabetes during follow-up (270 on rosuvastatin vs 216
      on placebo; HR 1.25, 95% CI 1.05-1.49, p=0.01), the point estimate of
      cardiovascular risk reduction associated with statin therapy (HR 0.63, 95% CI
      0.25-1.60) was consistent with that for the trial as a whole (0.56, 0.46-0.69).
      By comparison with placebo, statins accelerated the average time to diagnosis of
      diabetes by 5.4 weeks (84.3 [SD 47.8] weeks on rosuvastatin vs 89.7 [50.4] weeks
      on placebo). INTERPRETATION: In the JUPITER primary prevention trial, the
      cardiovascular and mortality benefits of statin therapy exceed the diabetes
      hazard, including in participants at high risk of developing diabetes. FUNDING:
      AstraZeneca.

PMID- 22883508
TI  - New drugs, procedures, and devices for hypertension.
AB  - Successful treatment of hypertension is difficult despite the availability of
      several classes of antihypertensive drug, and the value of strategies to combat
      the effect of adverse lifestyle behaviours on blood pressure. In this paper, we
      discuss two promising therapeutic alternatives for patients with resistant
      hypertension: novel drugs, including new pharmacological classes (such as
      vasopeptidase inhibitors and aldosterone synthase inhibitors) and new molecules
      from present pharmacological classes with additional properties in blood-pressure
      or metabolism pathways; and new procedures and devices, including stimulation of
      arterial baroreceptors and catheter-based renal denervation. Although several
      pharmacological targets have been discovered with promising preclinical results,
      the clinical development of novel antihypertensive drugs has been more difficult
      and less productive than expected. The effectiveness and safety of new devices
      and procedures should be carefully assessed in patients with resistant
      hypertension, thus leading to a new era of outcome trials and evidence-based
      guidelines.

PMID- 22883509
TI  - Diabetes and hypertension: the bad companions.
AB  - High blood pressure is reported in over two-thirds of patients with type 2
      diabetes, and its development coincides with the development of hyperglycaemia.
      Many pathophysiological mechanisms underlie this association. Of these
      mechanisms, insulin resistance in the nitric-oxide pathway; the stimulatory
      effect of hyperinsulinaemia on sympathetic drive, smooth muscle growth, and
      sodium-fluid retention; and the excitatory effect of hyperglycaemia on the renin
      angiotensin-aldosterone system seem to be plausible. In patients with diabetes,
      hypertension confers an enhanced risk of cardiovascular disease. A blood pressure
      of lower than 140/85 mm Hg is a reasonable therapeutic goal in patients with type
      2 diabetes according to clinical trial evidence. People with controlled diabetes
      have a similar cardiovascular risk to patients without diabetes but with
      hypertension. A renin-angiotensin system blocker combined with a thiazide-type
      diuretic might be the best initial antihypertensive regimen for most people with
      diabetes. In general, the positive effects of antihypertensive drugs on
      cardiovascular outcomes outweigh the negative effects of antihypertensive drugs
      on glucose metabolism.

PMID- 22883510
TI  - Hypertension in developing countries.
AB  - Data from different national and regional surveys show that hypertension is
      common in developing countries, particularly in urban areas, and that rates of
      awareness, treatment, and control are low. Several hypertension risk factors seem
      to be more common in developing countries than in developed regions. Findings
      from serial surveys show an increasing prevalence of hypertension in developing
      countries, possibly caused by urbanisation, ageing of population, changes to
      dietary habits, and social stress. High illiteracy rates, poor access to health
      facilities, bad dietary habits, poverty, and high costs of drugs contribute to
      poor blood pressure control. The health system in many developing countries is
      inadequate because of low funds, poor infrastructure, and inexperience. Priority
      is given to acute disorders, child and maternal health care, and control of
      communicable diseases. Governments, together with medical societies and non
      governmental organisations, should support and promote preventive programmes
      aiming to increase public awareness, educate physicians, and reduce salt intake.
      Regulations for the food industry and the production and availability of generic
      drugs should be reinforced.

PMID- 22883511
TI  - Lost in effusion.

PMID- 22883512
TI  - Extraskeletal multiple myeloma presenting with an atrial mass: a case report and
      a review of the literature.
AB  - INTRODUCTION: Extraskeletal presentation at diagnosis or during the course of
      multiple myeloma is a rare event. The prognosis is usually very poor. At the
      moment there is no agreed gold standard for the treatment of this presentation.
      CASE PRESENTATION: A 79-year-old Caucasian woman was treated at our hospital for
      right atrial myeloma localization. Our patient showed the following signs and
      symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial
      edema. Surgery was not considered feasible due to the extent of the disease. Our
      patient underwent external-beam radiation therapy using an intensity modulated
      technique, thus obtaining a persistent complete remission. Our patient has been
      in continuous complete local remission for 25 months since the end of
      radiotherapy. CONCLUSION: The role of radiotherapy is not defined in multiple
      myeloma with extraskeletal presentation. Our regimen seems to be effective in
      controlling the disease in this patient.This case report adds to the existing
      literature as it describes an unusual presentation of the disease and a new
      therapeutic approach to this rare presentation of multiple myeloma.

PMID- 22883513
TI  - Malignancies after kidney transplantation: Hong Kong renal registry.
AB  - Manystudies have shown that kidney transplant recipients have a higher incidence
      of cancers when compared with general population. However, most data on the
      posttransplant malignancies (PTM) are derived from Western literature and large
      population-based studies are rare. There is also lack of information about the
      posttransplant cancer-specific mortality rate. We conducted a population-based
      study of 4895 kidney transplants between 1972 and 2011, with data from the Hong
      Kong Renal Registry. Patterns of cancer incidence and mortality in our kidney
      transplant recipients were compared with those of the general population using
      standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs)
      respectively. With 40 246 person-years of follow-up, 299 PTM was diagnosed. The
      SIR of all cancers was 2.94 (female 3.58 and male 2.58). Non-Hodgkin lymphoma
      (NHL), kidney, and bladder cancers had the highest SIRs. The overall SMR was 2.3
      (female 3.4 and male 1.7) and the highest SMR was NHL. The patterns of PTM differ
      among countries. Increases in cancer incidence can now translate into similar
      increases in cancer mortality. NHL is important in our kidney transplant
      recipients. Strategies in cancer screening in selected patient groups are needed
      to improve transplant outcomes.

PMID- 22883514
TI  - Identification and characterization of a cis,trans-mixed heptaprenyl diphosphate
      synthase from Arabidopsis thaliana.
AB  - In eukaryotes, dolichols (C(70-120)) play indispensable roles as glycosyl carrier
      lipids in the biosynthesis of glycoproteins on endoplasmic reticulum. In addition
      to dolichols, seed plants have other types of Z,E-mixed polyisoprenoids termed
      ficaprenol (tri-trans,poly-cis-polyprenol, C(45-75)) and betulaprenol (di
      trans,poly-cis-polyprenol, C(30-45) and C(>=70)) in abundance. However, the
      physiological significance of these polyprenols has not been elucidated because
      of limited information regarding cis-prenyltransferases (cPTs) which catalyze the
      formation of the structural backbone of Z,E-mixed polyisoprenoids. In the
      comprehensive identification and characterization of cPT homologues from
      Arabidopsis thaliana, AtHEPS was identified as a novel cis,trans-mixed
      heptaprenyl diphosphate synthase. AtHEPS heterologously expressed in Escherichia
      coli catalyzed the formation of C(35) polyisoprenoid as a major product,
      independent of the chain lengths of all-trans allylic primer substrates. Kinetic
      analyses revealed that farnesyl diphosphate was the most favorable for AtHEPS
      among the allylic substrates tested suggesting that AtHEPS was responsible for
      the formation of C(35) betulaprenol. AtHEPS partially suppressed the phenotypes
      of a yeast cPT mutant deficient in the biosynthesis of dolichols. Moreover, in A.
      thaliana cells, subcellular localization of AtHEPS on the endoplasmic reticulum
      was shown by using green fluorescent protein fused proteins. However, a cold
      stress-inducible expression of AtHEPS suggested that AtHEPS and its product might
      function in response to abiotic stresses rather than in cell maintenance as a
      glycosyl carrier lipid on the endoplasmic reticulum.

PMID- 22883515
TI  - Seroprevalence of Japanese encephalitis virus and risk factors associated with
      seropositivity in pigs in four mountain districts in Nepal.
AB  - Japanese encephalitis was recently reported from individuals in the mountain
      districts of Nepal without travel history to Japanese encephalitis virus (JEV)
      endemic areas. We performed a cross-sectional study to estimate the
      seroprevalence of JEV in pigs and subsequently conducted a survey of farmers to
      identify risk factors associated with seropositivity. In July and August, 2010,
      454 pig serum samples were collected and tested by competitive ELISA. Data from a
      35-question survey of 109 pig owners were analysed using multivariate logistic
      regression. Seventy-six (16.7, 95% CI 13.6-20.4) pigs tested positive for anti
      JEV antibodies, none of which had been vaccinated against JEV or sourced from JEV
      endemic areas. Risk factors associated with JEV seropositivity were 'summer
      abortion', 'wells as a water source', 'urban location', 'reported presence of
      mosquitoes' and 'lower elevation'. Our results suggest that JEV is likely
      circulating in the mountain districts of Nepal, and that locally acquired JEV
      should be considered a risk for residents and travellers in these areas.

PMID- 22883516
TI  - [How to reduce the discrepancy between China and western countries in basic and
      clinical research of endometriosis].

PMID- 22883517
TI  - [Study on the relationship between altered expression of annexin A4 and
      endometrial receptivity during the implantation window in infertile patients with
      endometriosis].
AB  - OBJECTIVE: To identify the differential expressed proteins, and to investigate
      the relationship between altered expression of annexin A4 during window of
      implantation [WOI (at day-6 after ovulatory day)] in infertile patients with
      endometriosis and endometrial receptivity. METHODS: Two-dimensional fluorescence
      differential in-gel electrophoresis (2D-DIGE) and matrix-assist laser desorption
      ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect
      protein expression in endometrial WOI in 10 infertile cases with endometriosis as
      endometriosis group and 10 infertile cases with tubal factors as control group.
      The semi-quantitative validation of annexin A4 in the eutopic endometrial tissue
      during WOI was analyzed by western blot. RESULTS: By comparing protein profiles,
      there were 7 meaningful differential proteins during WOI in infertile patients
      with endometriosis. One protein with an isoelectric point of 5.84 and relative
      molecular weight of 36 100 were down regulated 348% in samples of endometriosis
      group. It was identified as annexin A4 by mass spectrometry. By western blot,
      relative intensity of annexin A4 in endometriosis group was 7.2 +/- 0.9, which
      was lower than 17.8 +/- 2.6 in control group significantly (t = 7.654, P =
      0.002). CONCLUSION: Lower expression of annexin A4 during WOI in infertile
      patients with endometriosis might be associated with the decrease of endometrial
      receptivity.

PMID- 22883518
TI  - [Association of the tumor necrosis factor-alpha -1031T/C and its combination with
      interleukin-6 -634C/G gene polymorphisms with susceptibility to endometriosis].
AB  - OBJECTIVE: To investigate the association of tumor necrosis factor-alpha (TNF
      alpha) gene promoter region -1031T/C and its combination with interleukin-6 (IL
      6) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the
      genetic susceptibility to endometriosis. METHODS: Total of 432 endometriosis
      patients and 499 non-endometriosis women who had received an operation due to
      tubal ligation, tubal recanalization, laparoscopic hydrotubation, ovarian simple
      cyst and teratoma were collected and separated into endometriosis group and
      control group, that all cases were confirmed by operation and pathology. A case
      control study was performed in endometriosis and control group to evaluate the
      association of these SNP with the susceptibility to endometriosis by using a
      fluorescent quantitative PCR-based high resolution melting (HRM) method. RESULTS:
      (1) TNF-alpha -1031T/C genotype:the T and C of TNF-alpha -1031T/C allele
      frequencies in the endometriosis group and control group were 79.2% (684/864),
      20.8% (180/864) and 81.8% (816/998), 18.2% (182/998), respectively. The TT, TC
      and CC of TNF-alpha -1031T/C genotype frequencies in the two groups were 63.7%
      (275/432), 31.0% (134/432), 5.3% (23/432) and 66.5% (332/499), 30.5% (152/499),
      3.0% (15/499), respectively. There were no statistical significances in the TNF
      alpha -1031T/C alleles and genotypes distributions between the two groups (P =
      0.158, P = 0.186). (2) TNF-alpha -1031T/C and IL-6 -634C/G conjoint genotypes: to
      research on the TNF-alpha -1031T/C and IL-6 -634C/G genotypes for conjoint
      analysis, the TT+CC, TC+CC, CC+CC, TT+CG, TC+CG, CC+CG, TT+GG, TC+GG and CC+GG
      combination genotype frequencies in the two groups were 39.4% (170/432), 19.4%
      (84/432), 4.6% (20/432), 20.6% (89/432), 8.8% (38/432), 0.9% (4/432), 3.5%
      (15/432), 2.3% (10/432), 0.5% (2/432) and 36.7% (183/499), 17.4% (87/499), 1.4%
      (7/499), 26.1% (130/499), 10.4% (52/499), 1.2% (6/499), 3.8% (19/499), 2.6%
      (13/499), 0.4% (2/499), respectively. There were no statistical significances in
      the combination genotypes distributions between the two groups (P = 0.107). As
      compared with carriers of TT+CC combination genotype, the endometriosis risk of
      carriers of CC+CC combination genotype enhanced 3.076 times (95%CI: 1.268 -
      7.457, P = 0.009), and the endometriosis risk of carriers of other combination
      genotypes were no statistical significances (all P > 0.05). CONCLUSIONS: The
      study demonstrates that there are no significant association between the SNP of
      TNF-alpha -1031T/C and genetic susceptibility to endometriosis. However the
      results indicate that there are significant association between genetic
      susceptibility to endometriosis and the combination polymorphisms of TNF-alpha 
      1031T/C and IL-6 -634C/G.

PMID- 22883519
TI  - [Expression of transient receptor potentials of vanilloid subtype 1 and pain in
      endometriosis].
AB  - OBJECTIVE: To investigate the expression of transient receptor potential
      vanilloid subtype 1 (TRPV1) in uterosacral ligament and its correlation with pain
      in endometriosis. METHODS: Total of 54 patients undergoing endometriotic lesions
      excision in uteroscaral ligament by laparoscopy due to pelvic pain were enrolled
      in this study. According to visual analogue scale (VAS) scores, 27 patients with
      VAS 5-10 were in group A and 27 patients with VAS 0-4 were in group B. In the
      mean time, 20 patients with dysmenorrhea without endometriosis (VAS: 0-4) were
      matched as group C. Specimens (including the sacro-ligaments of 20 women without
      endometriosis) were immunostained with specific antibodies of TRPV1. Western blot
      and real time PCR were performed to detect TRPV1 expression in endometriosis
      lesions and control group. RESULTS: (1) Immunohistochemnistry: the positive area
      of TRPV1 was found in endometriotic lesions in uterosacral ligament in group A, B
      and tissue of uterosacral ligament group C. The semi-qualitification of TRPV1
      expression were 3 in group A, 1 in group B and 1 in group C by
      immunohistochemistry staining. There was significantly different expression
      between group B and group A (P = 0.005) or group C (P = 0.027). (2) mRNA
      expression:the expression of TRPV1 was 1.84 in group A, 0.80 in group B, 0.24 in
      group C, respectively. With higher VAS scores, the expression of TRPV1 exhibited
      increasing trends. The expression of TRPV1 mRNA was higher in group A than that
      in group B (P = 0.022). There was statistically different expression between
      group B and group C (P = 0.031). (3) Western blot: the expression of TRPV1
      protein was 0.63 in group A, 0.19 in group B, 0.02 in group C. There was
      significant differences between group A and group B (P = 0.022), and between
      group B and group C (P < 0.01). CONCLUSION: The expression of TRPV1 was
      correlated with the degree of pain in patient with endometriosis.

PMID- 22883520
TI  - [Intrauterine growth characteristics of twins and those twins discordant
      birthweight].
AB  - OBJECTIVE: To investigate the intrauterine growth characteristics of twins and
      birthweight discordant twins (discordant twins). METHODS: Total of 1010 twin
      pregnancies (2020 fetuses) with complete delivery records from the Department of
      Obstetrics and Gynecology, the First and Third Affiliated Hospital of SUN Yat-sen
      University between January 1, 2000 and July 31, 2010 were studied
      retrospectively. One handred and ninteen cases (238 fetuses) with intrapair
      birthweight difference >= 25% were determined as the discordant twins group, and
      the other 891 cases (1782 fetuses) with intrapair birthweight difference < 25%
      were identified as the concordant twins group. The singleton control group
      included 4042 singleton pregnancies in the same period. RESULTS: (1) Comparison
      of clinical data between the twins groups: the birthweight of larger-twin,
      smaller-twin and intrapair birthweight difference in the discordant twins group
      and the concordant twins group were (2090 +/- 827) g, (1392 +/- 592) g, (33.9 +/-
      9.3)%, and (2408 +/- 543) g, (2191 +/- 505) g, (8.9 +/- 6.5)%, respectively, with
      significant differences (P < 0.01). The incidence of discordant twins was 11.78%
      (119/1010). Compared with the concordant twins group, the discordant twins group
      had higher proportion of monochorionic twins, and higher prevalence of pregnancy
      complications such as late miscarriage, abnormal umbilical insertion, twin-twin
      transfusion syndrome and hypertensive disorders in pregnancy (P < 0.05). (2) The
      characteristics of twin birthweight distribution: 1) In all the 2020 twins,
      80.05% (1617/2020) fetuses had birthweight below the 50(th) percentile of the
      singleton control group, while 23.71% (479/2020) feeuses got birthweight below
      the 10(th) percentile of the singleton control group. 2) After 19(th) gestational
      week, the 50(th) and 90(th) percentile of all twins' birthweight were lower than
      those of singletons. After 38(th) gestational week, the birthweight of singletons
      kept increasing and reached its peak at 41(th) week, while the birthweight of
      twins reached its peak at 38(th) week, followed by a decline at 39 weeks, which
      was even lower than the 10(th) percentile of the singleton control group. 3) The
      distribution of birthweight of larger- and smaller-twin in the discordant twins
      group: 65 (54.6%, 65/119) larger-twins and one (0.8%, 1/119) smaller-twin had
      birthweight above the 50(th) percentile of all twins, while 5 (4.2%, 5/119)
      larger-twins and 97 (81.5%, 97/119) smaller-twins got birthweight below the
      10(th) percentile of all twins. CONCLUSIONS: (1) The patterns of birthweight
      curves for each gestational week are different between twins and singletons. In
      order to evaluate the growth of twins, birthweight reference for twins should be
      employed. (2) According to the reference of twins birthweight, the most
      discordant twins are complicated with fetal growth restriction at least in one
      twin.

PMID- 22883521
TI  - [Association between severe preeclampsia and single nucleotide polymorphism of
      macrophage migration inhibitory factors -173G/C].
AB  - OBJECTIVE: To investigate whether single nucleotide polymorphism (SNP) of
      macrophage migration inhibitory factor (MIF) gene -173G/C is associated with
      severe preeclampsia. METHODS: Totally 124 severe preeclampsia patients and 160
      healthy pregnant women (control group) were included in our study who were
      recruited consecutively from Affiliated Hospital of Qingdao University Medical
      College between March 2010 and March 2011. The SNP was detected through SYBR
      Green PCR. The levels of fasting blood glucose (FBG), fasting insulin (FIN), and
      serum total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL)
      and light density lipoprotein (LDL) were determined in every participants. The
      homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. The
      allele and genotype frequencies between severe preeclampsia patients and control
      group were compared. The FBG, FIN, body mass index (BMI), HOMA-IR, TC, TG, HDL
      and LDL in different genotype were compared. RESULTS: (1) The MIF -173G/C SNP
      genotype frequencies of GG, CG, and CC were 62.1% (77/124), 30.6% (38/124), 7.3%
      (9/124), the allelic frequencies of G and C were 77.4% (192/248) and 22.6%
      (56/248), respectively, in severe preeclampsia patients; the MIF -173G/C SNP
      genotype frequencies of GG, CG, and CC were 64.4% (103/160), 30.6% (49/160), 5.0%
      (8/160), the allelic frequencies of G and C were 79.7% (255/320) and 20.3%
      (65/320), respectively, in the control group. No significant differences were
      observed in the genotypes and allele distributions of MIF -173G/C SNP between the
      severe preeclampsia patients and control group (all P > 0.05). (2) The severe
      preeclampsia patients with CG and CC genotypes had higher BMI compared with the
      GG genotype [(25 +/- 4) versus (22 +/- 4) kg/m(2); t = 3.96, P < 0.05].(3) The
      severe preeclampsia patients with CG and CC genotypes had higher FIN level and
      higher HOMA-IR compared with the GG genotype [(15.7 +/- 2.9) versus (13.6 +/-
      4.0) mmol/L, 3.3 +/- 0.5 versus 2.7 +/- 0.6; t = 3.17, t = 5.58, all P < 0.05].
      (4) There was no significant difference in FBG, TC, TG, HDL and LDL levels in
      severe preeclampsia patients with different genotypes (all P > 0.05).
      CONCLUSIONS: The present study suggests that the MIF -173G/C SNP is associated
      with insulin resistance in severe preeclampsia patients. The CG and CC genotypes
      increase the degree of insulin resistance, but it is may not associate with
      susceptibility among severe preeclampsia patients of Han Chinese women.

PMID- 22883522
TI  - [Expression of pentraxin-3 in placentas and its relationship with severe
      preeclampsia].
AB  - OBJECTIVE: To explore the expression of pentraxin-3 (PTX3) in placentas from
      patients with severe preeclampsia and the relationship between PTX3 and the
      pathogenesis of severe preeclampsia. METHODS: Fifty-three pregnant women who
      delivered from October 2010 to March 2011 in the First Affiliated Hospital of
      Chongqing Medical University were included in the study. Twenty-three women with
      severe preeclampsia were chosen as the preeclampsia group, and thirty healthy
      pregnant women were identified as the control group. All the women received
      cesarean section. The location of PTX3 protein in placentas was studied by
      immunohistochemical SP method. Quantitative real-time PCR technique and western
      blot analysis were employed to assay the levels of PTX3 mRNA and protein in
      placentas, respectively. RESULTS: (1) The location of PTX3 protein in placentas:
      PTX3 protein was expressed in placentas from both groups, and there was no
      difference of PTX3 distribution between normal and preeclamptic placentas. PTX3
      was mainly located in perivascular stroma, decidual cells and terminal villi.
      Neutrophilic infiltration was observed in the preeclamptic placentas. (2) The
      expression of PTX3 mRNA and protein in placentas:the level of PTX3 mRNA in
      placentas from the preeclampsia group was higher than that in the control group
      (1.98 +/- 0.54 vs. 0.87 +/- 0.27, P < 0.05). Compared with the control group, the
      level of PTX3 protein was significantly elevated in the preeclampsia group (1.42
      +/- 0.29 vs. 0.56 +/- 0.25, P < 0.01). CONCLUSION: The high expression of PTX3 in
      placentas from the preeclamptic patients suggests that PTX3 may be involved in
      the pathologic process of preeclampsia.

PMID- 22883523
TI  - [Preliminary study of estrogen effects on calcium free smooth muscle cells at the
      endometrial-myometrial interface in uteri with adenomyosis].
AB  - OBJECTIVE: To investigate the effect and mechanism of estrodial (E(2)) on
      intracellular free calcium in the endometrial-myometrial interface (EMI) smooth
      muscle cells from uteri with adenomyosis. METHODS: From March 2011 to October
      2011, 16 uterus specimens were collected from patients with adenomyosis
      undergoing hysterectomy in Beijing Obstetrics and Gynecology Hospital, which
      included 9 proliferative endometrium and 7 secretory endometrium. EMI smooth
      muscle cells from the uterus were cultured and loaded with calcium ion (Ca(2+))
      fluorescent probe fluo-4/AM. The labeled cells were stimulated with the various
      concentration of E(2)(1*10(2), 1*10(3), 1*10(4), 1*10(5) pmol/L, respectively),
      then the changes of intracellular Ca(2+) fluorescence intensity were measured by
      laser scanning microscopy. The most suitable concentration of E(2) was selected,
      and the reaction difference between the EMI smooth muscle cells of two menstrual
      phases were also investigated; The changes of intracellular Ca(2+) fluorescence
      intensity were detected proliferative and secretory smooth muscle cells in E(2)
      conjugated to bovine serum albumin (17beta-E(2)-BSA) group, cycloheximide (CHX)
      group, fulvestrant (ICI182780) group and pertussis toxin (PTX) group. RESULTS:
      (1) The cell viability of primary cultured EMI smooth muscle cells was well at 24
      hours culture. (2) 1*10(2) - 1*10(5) pmol/L E(2) can rapidly increase the
      intracellular Ca(2+) fluorescence intensity within 1 min (P < 0.01);The increased
      amplitudes caused by 1*10(4) pmol/L and 1*10(5) pmol/L E(2) were the most
      significant, but there was no significant difference between them (P > 0.05).
      1*10(4) pmol/L was the most suitable concentration. (3) With the 1*10(4) pmol/L
      E(2), the Ca(2+) fluorescence intensity changes showed no significant difference
      between the EMI smooth muscle cells from the proliferative phase and secretory
      phase uterus (P > 0.05). The Ca(2+) fluorescence intensity changes were 646 +/-
      32 in 17beta-E(2)-BSA group and 602 +/- 31 in CHX group, when compared with 513
      +/- 26 and 617 +/- 35 in respective control group, no significant difference was
      observed (P > 0.05). The increased amplitude of 188 +/- 20 in the PTX group and
      302 +/- 11 in ICI182780 group exhibited significant difference with 632 +/- 33
      and 635 +/- 24 in respective control group (P < 0.01). CONCLUSION: E(2) could
      increase the intracellular Ca(2+) of EMI through a membrane receptor dependent
      and nongenomic mechanism of action.

PMID- 22883524
TI  - [Re-evaluation of interval debulking surgery in advanced epithelial ovarian
      cancer].
AB  - OBJECTIVE: Previous study showed that interval debulking surgery (IDS) may
      improve the survival of patients with advanced epithelial ovarian cancer (EOC).
      The precise significance of IDS needs to be evaluated. METHODS: Totally 136
      consecutive patients with stage IIIc or IV EOC (including primary peritoneal
      carcinoma and primary fallopian tube carcinoma) who completed primary debulking
      surgery (PDS) and platinum-based chemotherapy were enrolled from January 2000 to
      December 2009 in a retrospective cohort study. The study group was divided into
      three groups: 65 cases underwent optimal PDS (Group A), 41 cases received
      chemotherapy alone after suboptimal PDS (Group B), and 30 patients underwent IDS
      after suboptimal PDS (Group C). All patients received six to eight courses of
      platinum-based combination chemotherapy (paclitaxel plus carboplatin/cisplatin,
      cyclophosphamide plus epirubicin and cisplatin). Patients' clinical
      characteristics, perioperative situation and prognosis were compared. RESULTS:
      Sixty-five cases (47.8%, 65/136) from 136 patients achieved optimal PDS. For
      Group C, 77% (23/30) patients obtained optimal debulking surgery after IDS.
      Intraoperative injury rates were similar between Group B and Group C (P > 0.05).
      Mild perioperative complications rate was also similar (P > 0.05). Median
      progression-free survival (PFS) of Group A was 26 months. Median overall survival
      (OS) of Group B and Group C were 31 months and 40 months, respectively (P =
      0.254). Median PFS of Group B and Group C were 13 months and 24 months,
      respectively (P = 0.289). Although when it came to 20 months after PDS, patients
      who underwent IDS had a significantly lower progressive disease (PD) rate (Group
      B 33% versus Group C 61%, P = 0.046), it still showed that there was no
      significant difference in either OS or PFS of these two groups. Those patients in
      Group C who obtained no visible residual got similar PFS (27 months) comparing to
      Group A (26 months, P = 0.730), but OS was still shorter (P = 0.010).
      CONCLUSIONS: For advanced EOC patients, IDS has little effect on improving
      survival. While it is safe and acceptable, also may prolong PFS in those patients
      who got no visible residual after IDS. The results suggest that IDS might be used
      as an alternative treatment for advanced EOC patients who cannot obtain optimal
      PDS in certain local hospitals.

PMID- 22883525
TI  - [Changes in awareness of cervical cancer patients after medical treatments and
      the correlation of cervical screening situation and clinical stage at
      consultation].
AB  - OBJECTIVE: To Investigate the cervical cancer patients' knowledge and situation
      concerning cervical cancer screening and explore the connection of cervical
      cancer screening status and clinical stage at diagnosis of cervical lesions.
      METHODS: Questionnaires were done for the cervical cancer patients who went to
      Peking University People's Hospital from February 2010 to October 2011. The
      patient's age, first visit or not, cause for treatment, awareness of cervical
      cancer now as well as that before diagnosis of the disease, the last cervical
      cancer screening' time and the clinical stage were recorded. The results of
      questionnaires were analyzed with SPSS 16.0. RESULTS: (1) One hundred and thirty
      eight cases were collected and the average age was (48 +/- 10) years old.
      Concerning the awareness level, the patients were divided into three groups of 10
      points, 5 points and 0 point based on the score of the second parts of the
      questionnaires. The number of the patients of the above three groups were 114
      (82.6%), 18 (13.0%) and 6 (4.3%) at present, while before the cancer diagnosis
      the number of the patients of the above three groups were 5 (3.6%), 13 (9.4%) and
      120 (87.0%). Patient's awareness level was much higher now than that before the
      cancer diagnosis (P < 0.05). (2) Based on the last cervical cancer screening
      time, the patients were divided into four groups including within one year (group
      1), a year ago but within three years (group 2), three years ago (group 3) and
      never done (group 4). There were 9 (6.5%) cases in group 1, 30 (21.7%) cases in
      group 2, 29 (21.0%) cases in group 3 and 70 (50.7%) cases in group 4. There were
      5 (5/9) cases with stage Ia, 3 (3/9) cases with stage Ib and 1 (1/9) case with
      stage II or above in group 1; 11 (36.7%, 11/30) cases with stage Ia, 15 (50.0%,
      15/30) cases with stage Ib and 4 (13.3%, 4/30) cases with stage II or above in
      group 2; 5 (17.2%, 5/29) cases with stage Ia, 14 (48.3%, 14/29) cases with stage
      Ib was and 10 (34.5%, 10/29) cases with stage II or above in group 3; 7 (10.0%,
      7/70) cases stage with Ia, 35 (50.0%, 35/70) cases with stage Ib and 28 (40.0%,
      28/70) cases with stage II or above in group 4. The results showed that there was
      an increasing trend of advanced cervical carcinoma at diagnosis for the patients
      with longer last cervical cancer screening time (P < 0.05). CONCLUSIONS: People's
      awareness level is much higher after being educated in cervical cancer. Among the
      cervical cancer patients, the probability of diagnosed patients with advanced
      cervical cancer has an increasing trend when their screening situation is poor.
      To raise the screening attendance rate among appropriate women, we should spread
      knowledge of cervical cancer to the population.

PMID- 22883526
TI  - [Roles of advanced glycation end products and its receptor on the fetal brain
      injury in pregnant rats with gestational diabetes mellitus].
AB  - OBJECTIVE: To study the roles of advanced glycation end products and its receptor
      on fetal brain injury of gestational diabetes mellitus (GDM) rats. METHODS:
      Twenty one adult pregnant Wistar rats were administered streptozotocin (STZ)
      intraperitoneally to induce GDM rats model. The fourteen pregnant rats were
      divided into two groups according to the fasting glucose on the 3(rd) day of
      pregnancy:severe GDM group with the fasting glucose > 16.7 mmol/L and mild GDM
      group with the fasting glucose between 6.7 - 16.7 mmol/L. Another seven pregnant
      rats were chosen as the severe GDM and intervention with micronutrient group,
      receiving gavage with micronutrient during the whole pregnancy. Five control rats
      received the same volume of citric acid buffer. All the pregnant rats were tested
      fasting glucose from the tail vein and their weight on the pregnant day 3, 13 and
      19. Maternal serum levels of AGE were measured by ELISA and RAGE levels in the
      embryonic brain tissues were tested by immunohistochemistry. RESULTS: (1) There
      was no statistically significant difference of pre-pregnancy fasting glucose
      level among all groups (P > 0.05). The fasting glucose levels on the 3(rd) day
      and the mean fasting glucouse level of pregnancy in the severe GDM group and the
      severe GDM and intervention with micronutrient group were higher than those of
      the control group (P < 0.05). And there was no significant difference between the
      severe GDM group and the severe GDM and intervention with micronutrient group (P
      > 0.05). (2) The serum AGE levels in the severe GDM group and the mild GDM group
      were (1037 +/- 38) ng/L and (880 +/- 34) ng/L respectively, with no significant
      difference (P > 0.05). The serum AGE levels in the control group and the severe
      GDM and intervention with micronutrient group were (857 +/- 32) ng/L and (988 +/-
      37) ng/L, and the difference was statistically significant (P < 0.05). The serum
      AGE levels in the severe GDM and intervention with micronutrient group and in the
      mild GDM group had no significant difference (P > 0.05). (3) The serum AGE levels
      in the severe GDM group, mild GDM group and the control group were positively
      associated with the mean glucose level of pregnancy (r = 0.603, P < 0.05) and the
      grlucose on the 3(rd) day of pregnancy (r = 0.704, P < 0.05). (4) The fetal brain
      nerve cell number and morphology in the control group were normal. While in the
      mild GDM group fetal brain nerve cells decreased, the proliferation and swelling
      of glial cells were seen. In the severe GDM group and the severe GDM and
      intervention with micronutrient group, the fetal brain cells furtherly reduced,
      and large vacuole around the cells, deformation and debris of the cells were
      seen. Glial scar formation was visible in some fetal brain tissues. There was a
      few RAGE expression in the control fetal brain tissues. In the mild GDM group and
      the severe GDM group, RAGE expression increased significantly. And the RAGE
      expression intensity in the severe GDM and intervention with micronutrient group
      was between the severe and the mild GDM groups. CONCLUSIONS: (1) Abnormal fetal
      brain development of GDM rats was associated with the increase of maternal serum
      AGE and the enhancement of RAGE expression in fetal brain tissues, which
      suggested that AGE/RAGE pathway may play an important role in the fetal brain
      injury of GDM rats. (2) Micronutrients can reduce the brain damage of GDM
      fetuses.

PMID- 22883527
TI  - [Regulation of claudin-4 gene expression in endometrial adenocarcinoma Ishikawa
      cell line by progesterone].
AB  - OBJECTIVE: To explore the regulation of claudin-4 expression in endometrial
      adenocarcinoma cell lines by progesterone. METHODS: Ishikawa cells were treated
      with various concentrations of megestrol acetate (MA: 2, 5, 10, 15, 20 mg/L).
      After cultured for 24, 48 and 72 hours, cells growth were measured by methyl
      thiazolyl tetrazolium (MTT). The group of Ishikawa cells incubated with MA at the
      50% inhibitory concentration (IC(50)) was selected for cell apoptosis assay by
      using transmission electron microscopy and flow cytometry method. Real-time PCR
      and western blot were used for detecting the mRNA and protein expression levels
      of claudin-4. The localization of claudin-4 was examined by immunofluorescent
      staining. RESULTS: The inhibitory effects of megestrol acetate on the growth of
      Ishikawa cells were dose-dependent and time-dependent. IC(50) of MA on Ishikawa
      cells was 15 mg/L after incubated for 72 hours. After MA treatment, Ishikawa
      cells showed shrinkage, nuclear chromatin condensation, fractures of nuclear
      membrane and endoplasmic reticulum expansion, even round apoptotic bodies were
      found. The apoptosis rate of cells before MA treatment was (0.076 +/- 0.024)%,
      and the rate was (3.934 +/- 0.816)% by MA treated for 72 hours, in which there
      were signicant difference (P < 0.05). The relative quantification of claudin-4
      mRNA and protein of the cells before MA treatment were 0.64 +/- 0.20 and 0.94 +/-
      0.18, while they were 0.47 +/- 0.15 and 0.62 +/- 0.15 after MA treated. The
      expression of claudin-4 was significantly decreased after MA treatment (P <
      0.05). The localization of claudin-4 transferred from cytomembrane to cytoplasm
      and nucleus after MA treatment. CONCLUSIONS: MA could inhibite the growth of
      Ishikawa cells, in which the mechanism may be decrease the expression of claudin
      4 and the apoptosis of cells. The distribution change of claudin-4 may be related
      to the anti-cancer effect of progesterone.

PMID- 22883528
TI  - Current smoking status may be associated with overt albuminuria in female
      patients with type 1 diabetes mellitus: a cross-sectional study.
AB  - BACKGROUND: There are very few clinical reports that have compared the
      association between cigarette smoking and microangiopathy in Asian patients with
      type 1 diabetes mellitus (T1DM). The objective of this study was to assess the
      relationships between urinary protein concentrations and smoking and gender-based
      risk factors among patients with T1DM. METHODS: A cross-sectional study of 259
      patients with T1DM (men/women = 90/169; mean age, 50.7 years) who visited our
      hospital for more than 1 year between October 2010 and April 2011 was conducted.
      Participants completed a questionnaire about their smoking habits. Patient
      characteristics included gender, age, body mass index, blood pressure, hemoglobin
      A1c, lipid parameters, and microangiopathy. Diabetic nephropathy (DN) was
      categorized as normoalbuminuria (NA), microalbuminuria (MA), or overt albuminuria
      (OA) on the basis of the following urinary albumin/creatinine ratio (ACR) levels:
      NA, ACR levels less than 30 mg/g creatinine (Cr); MA, ACR levels between 30 and
      299 mg/g Cr; and OA, ACR levels over 300 mg/g Cr. RESULTS: The percentages of
      current nonsmokers and current smokers with T1DM were 73.0% (n = 189) and 27.0%
      (n = 70), respectively. In addition, the percentage of males was higher than that
      of females (52.2% versus 13.6%) in the current smoking population. The percentage
      of DN was 61.8% (n = 160) in patients with NA, 21.6% (n = 56) in patients with
      MA, and 16.6% (n = 43) in patients with OA. The percentage of males among OA
      patients was also higher than that of females (24.4% versus 12.4%). However,
      current smoking status was associated with OA in females with T1DM only
      [unadjusted odds ratio (OR), 4.13; 95% confidence interval (CI), 1.45-11.73, P <
      0.01; multivariate-adjusted OR, 5.41; 95% CI, 1.69-17.30, P < 0.01]. CONCLUSIONS:
      Based on our results in this cross-sectional study of Asian patients with T1DM,
      smoking might be a risk factor for OA among female patients. Further research is
      needed of these gender-specific results.

PMID- 22883529
TI  - Occurrence of maxillary sinus abnormalities detected by cone beam CT in
      asymptomatic patients.
AB  - BACKGROUND: Although cone beam computed tomography (CBCT) images of the
      maxillofacial region allow the inspection of the entire volume of the maxillary
      sinus (MS), identifying anatomic variations and abnormalities in the image
      volume, this is frequently neglected by oral radiologists when interpreting
      images of areas at a distance from the dentoalveolar region, such as the full
      anatomical aspect of the MS. The aim of this study was to investigate maxillary
      sinus abnormalities in asymptomatic patients by using CBCT. METHODS: 1113 CBCT
      were evaluated by two examiners and identification of abnormalities, the presence
      of periapical lesions and proximity to the lower sinus wall were recorded. Data
      were analyzed using descriptive statistics, chi-square tests and Kappa
      statistics. RESULTS: Abnormalities were diagnosed in 68.2% of cases (kappa =
      0.83). There was a significant difference between genders (p < 0.001) and there
      was no difference in age groups. Mucosal thickening was the most prevalent
      abnormality (66%), followed by retention cysts (10.1%) and opacification (7.8%).
      No association was observed between the proximity of periapical lesions and the
      presence and type of inflammatory abnormalities (p = 0.124). CONCLUSIONS:
      Abnormalities in maxillary sinus emphasizes how important it is for the
      dentomaxillofacial radiologist to undertake an interpretation of the whole volume
      of CBCT images.

PMID- 22883530
TI  - Split-thickness cartilage grafts for chest wall reconstruction in pentalogy of
      Cantrell.
AB  - We describe a simple technique for chest wall reconstruction in pentalogy of
      Cantrell using split-thickness cartilage grafts. This technique provides a robust
      reconstruction, gives immediate and excellent cosmetic results, allows for
      skeletal and tissue growth, and avoids the use of synthetic material.

PMID- 22883531
TI  - Accuracy study of new computer-assisted orthopedic surgery software.
AB  - PURPOSE: The new computerized system is based on image analysis and designed to
      aid in orthopedic surgeries by virtual trajectory of the guide wire, intra
      operative planning and various measurements. Validation of the accuracy and
      safety of any computer-aided surgery system is essential before implementing it
      clinically. We examined the accuracy of guide-wire length and angle measurements
      and fusion of multiple adjacent images (panoramic view image, PVI((r))) of the
      new software. METHODS: This is a 2-part study. Part I: twenty guide wires were
      drilled to various depths in a synthetic femur model and the results obtained by
      the software measurements were compared with manual measurements by a caliper and
      a depth gauge. Part II: a sawbone femur shaft was osteotomized and various
      inclinations of > 10 degrees  to the varus or valgus angles were tested. The
      manually obtained measurements of angles and lengths were compared to the new
      computerized system software PVI. RESULTS: There was a significant positive
      linear correlation between all groups of the computerized length and the control
      measurements (r>0.983, p<0.01). There was no significant difference among
      different distances, angles or positions from the image intensifier. There was a
      significant positive linear correlation between the angle and length measurement
      on the PVI and the control measurement (r>0.993, p<0.01). CONCLUSIONS: The new
      computerized software has high reliability in performing measurements of length
      using an aiming, positioning and referring device intra-operatively.

PMID- 22883532
TI  - Dose reduction in chest CT: comparison of the adaptive iterative dose reduction
      3D, adaptive iterative dose reduction, and filtered back projection
      reconstruction techniques.
AB  - OBJECTIVES: To assess the effectiveness of adaptive iterative dose reduction
      (AIDR) and AIDR 3D in improving the image quality in low-dose chest CT (LDCT).
      MATERIALS AND METHODS: Fifty patients underwent standard-dose chest CT (SDCT) and
      LDCT simultaneously, performed under automatic exposure control with noise index
      of 19 and 38 (for a 2-mm slice thickness), respectively. The SDCT images were
      reconstructed with filtered back projection (SDCT-FBP images), and the LDCT
      images with FBP, AIDR and AIDR 3D (LDCT-FBP, LDCT-AIDR and LDCT-AIDR 3D images,
      respectively). On all the 200 lung and 200 mediastinal image series, objective
      image noise and signal-to-noise ratio (SNR) were measured in several regions, and
      two blinded radiologists independently assessed the subjective image quality.
      Wilcoxon's signed rank sum test with Bonferroni's correction was used for the
      statistical analyses. RESULTS: The mean dose reduction in LDCT was 64.2% as
      compared with the dose in SDCT. LDCT-AIDR 3D images showed significantly reduced
      objective noise and significantly increased SNR in all regions as compared to the
      SDCT-FBP, LDCT-FBP and LDCT-AIDR images (all, P <= 0.003). In all assessments of
      the image quality, LDCT-AIDR 3D images were superior to LDCT-AIDR and LDCT-FBP
      images. The overall diagnostic acceptability of both the lung and mediastinal
      LDCT-AIDR 3D images was comparable to that of the lung and mediastinal SDCT-FBP
      images. CONCLUSIONS: AIDR 3D is superior to AIDR. Intra-individual comparisons
      between SDCT and LDCT suggest that AIDR 3D allows a 64.2% reduction of the
      radiation dose as compared to SDCT, by substantially reducing the objective image
      noise and increasing the SNR, while maintaining the overall diagnostic
      acceptability.

PMID- 22883533
TI  - Implementation of a web-based, interactive polytrauma tutorial in computed
      tomography for radiology residents: how we do it.
AB  - PURPOSE: Due to the time factor in polytraumatized patients all relevant
      pathologies in a polytrauma computed tomography (CT) scan have to be read and
      communicated very quickly. During radiology residency acquisition of effective
      reading schemes based on typical polytrauma pathologies is very important. Thus,
      an online tutorial for the structured diagnosis of polytrauma CT was developed.
      MATERIALS AND METHODS: Based on current multimedia theories like the cognitive
      load theory a didactic concept was developed. As a web-environment the learning
      management system ILIAS was chosen. CT data sets were converted into online
      scrollable QuickTime movies. Audiovisual tutorial movies with guided image
      analyses by a consultant radiologist were recorded. RESULTS: The polytrauma
      tutorial consists of chapterized text content and embedded interactive scrollable
      CT data sets. Selected trauma pathologies are demonstrated to the user by guiding
      tutor movies. Basic reading schemes are communicated with the help of detailed
      commented movies of normal data sets. Common and important pathologies could be
      explored in a self-directed manner. CONCLUSIONS: Ambitious didactic concepts can
      be supported by a web based application on the basis of cognitive load theory and
      currently available software tools.

PMID- 22883534
TI  - The effect of spinal manipulative therapy on experimentally induced pain: a
      systematic literature review.
AB  - BACKGROUND: Although there is evidence that spinal manipulative therapy (SMT)
      can reduce pain, the mechanisms involved are not well established. There is a
      need to review the scientific literature to establish the evidence-base for the
      reduction of pain following SMT. OBJECTIVES: To determine if SMT can reduce
      experimentally induced pain, and if so, if the effect is i) only at the level of
      the treated spinal segment, ii) broader but in the same general region as SMT is
      performed, or iii) systemic. DESIGN: A systematic critical literature review.
      METHODS: A systematic search was performed for experimental studies on healthy
      volunteers and people without chronic syndromes, in which the immediate effect of
      SMT was tested. Articles selected were reviewed blindly by two authors. A summary
      quality score was calculated to indicate level of manuscript quality. Outcome was
      considered positive if the pain-reducing effect was statistically significant.
      Separate evidence tables were constructed with information relevant to each
      research question. Results were interpreted taking into account their manuscript
      quality. RESULTS: Twenty-two articles were included, describing 43 experiments,
      primarily on pain produced by pressure (n = 27) or temperature (n = 9). Their
      quality was generally moderate. A hypoalgesic effect was shown in 19/27
      experiments on pressure pain, produced by pressure in 3/9 on pain produced by
      temperature and in 6/7 tests on pain induced by other measures. Second pain
      provoked by temperature seems to respond to SMT but not first pain. Most studies
      revealed a local or regional hypoalgesic effect whereas a systematic effect was
      unclear. Manipulation of a "restricted motion segment" ("manipulable lesion")
      seemed not to be essential to analgesia. In relation to outcome, there was no
      discernible difference between studies with higher vs. lower quality scores.
      CONCLUSIONS: These results indicate that SMT has a direct local/regional
      hypoalgesic effect on experimental pain for some types of stimuli. Further
      research is needed to determine i) if there is also a systemic effect, ii) the
      exact mechanisms by which SMT attenuates pain, and iii) whether this response is
      clinically significant.

PMID- 22883535
TI  - Effects of dissolved oxygen on the biooxidation process of refractory gold ores.
AB  - While multiple theories exist regarding the effect of dissolved oxygen (DO) on
      the biooxidation of minerals, few studies have been performed the cellular or
      molecular scale (e.g., genetics) and the mechanism remains unclear. In this
      paper, the effects of DO concentration on the biooxidation process of refractory
      sulfide gold ores by Acidithiobacillus ferrooxidans were investigated in the
      experimental stirred tank bioreactors (STRs). The results indicated that higher
      biooxidation and cell growth rates were correlated with higher DO concentration.
      The biooxidation process was restricted at 1.2 ppm DO due to oxygen limitation.
      Furthermore, the effects of DO on cellular and molecular scale were studied for
      the first time. The results demonstrated that the oxygen uptake rate (OUR), the
      Fe(2+) oxidation activity and the rus gene expression of A. ferrooxidans all
      increased with the DO concentration, which might be responsible for the increase
      of the biooxidation rates with the DO concentration. This study provides insight
      into the potential impact of molecular-level mechanisms of DO in the biooxidation
      process of minerals.

PMID- 22883536
TI  - Enzymatic pathway for biodegrading microcystin LR in Sphingopyxis sp. C-1.
AB  - The mlr gene cluster consisting of mlrA, mlrB, mlrC, and mlrD is involved in the
      degradation of the cyanobacterial toxin microcystin. However, it is unclear which
      degradation intermediates are metabolized by MlrB and MlrC. To address these
      questions, we constructed recombinant Escherichia coli to overproduce MlrB and
      MlrC from Sphingopyxis sp. C-1, and determined which intermediates were degraded
      in cell-free extracts. The cell-free extract containing MlrB degraded linearized
      microcystin-LR, giving rise to a tetrapeptide. The cell-free extract of MlrC
      degraded linearized microcystin-LR and also degraded the tetrapeptide to the
      amino acid Adda. These results indicate that linearized microcystin-LR is
      degraded by both MlrB and MlrC, and tetrapeptide is degraded by specifically by
      MlrC in Sphingopyxis sp. C-1.

PMID- 22883537
TI  - Emerging perspectives in the restoration of biodiversity-based ecosystem
      services.
AB  - Given the large-scale anthropogenic alteration of natural habitats, ecological
      restoration is emerging as one of the most important disciplines in environmental
      science. Once habitats are physically restored, an important goal of restoration
      is to recover the ecosystem services provided by the diversity of species and
      their interactions (e.g., seed dispersal, pollination, pest control, and invasion
      resistance). However, current understanding of the ecological processes
      underlying this recovery is often incomplete and poorly integrated across
      different ecosystems. Here, we highlight recent conceptual findings in
      biodiversity-ecosystem functioning, food-web theory, and metacommunity theory
      that are relevant to restoration. We also identify knowledge gaps that will
      contribute to moving restoration from a site- and situation-specific discipline
      to a more globally applicable science.

PMID- 22883538
TI  - Combined role of childhood maltreatment, family history, and gender in the risk
      for alcohol dependence.
AB  - BACKGROUND: Studies of the relationship between childhood maltreatment and
      alcohol dependence have not controlled comprehensively for potential confounding
      by co-occurring maltreatments and other childhood trauma, or determined whether
      parental history of alcohol disorders operates synergistically with gender and
      maltreatment to produce alcohol dependence. We addressed these issues using
      national data. Method Face-to-face surveys of 27 712 adult participants in a
      national survey. RESULTS: Childhood physical, emotional and sexual abuse, and
      physical neglect were associated with alcohol dependence (p<0.001), controlling
      for demographics, co-occurring maltreatments and other childhood trauma.
      Attributable proportions (APs) due to interaction between each maltreatment and
      parental history revealed significant synergistic relationships for physical
      abuse in the entire sample, and for sexual abuse and emotional neglect in women
      (APs, 0.21, 0.31, 0.26 respectively), indicating that the odds of alcohol
      dependence given both parental history and these maltreatments were significantly
      higher than the additive effect of each alone (p<0.05). CONCLUSIONS: Childhood
      maltreatments independently increased the risk of alcohol dependence.
      Importantly, results suggest a synergistic role of parental alcoholism: the
      effect of physical abuse on alcohol dependence may depend on parental history,
      while the effects of sexual abuse and emotional neglect may depend on parental
      history among women. Findings underscore the importance of early identification
      and prevention, particularly among those with a family history, and could guide
      genetic research and intervention development, e.g. programs to reduce the burden
      of childhood maltreatment may benefit from addressing the negative long-term
      effects of maltreatments, including potential alcohol problems, across a broad
      range of childhood environments.

PMID- 22883539
TI  - Caregiver food behaviours are associated with dietary intakes of children outside
      the child-care setting.
AB  - OBJECTIVE: To evaluate whether food behaviours of parents are associated with
      children's dietary intakes outside the child-care setting, and to compare
      children's dietary intakes at home with foods and beverages consumed when they
      are at child-care centres. DESIGN: In 2005-2006, a survey was completed by
      parents of at least one child between 3 and 5 years old who attended group child
      care centres. Surveys about nutrition practices were completed by centre
      directors. Research assistants observed foods and beverages consumed by children
      at lunchtime at the centres. SETTING: Sixteen licensed group child-care centres
      in three underserved New York City communities (South Bronx, East/Central Harlem,
      Central Brooklyn) and the Lower East Side of Manhattan. SUBJECTS: Two hundred
      parents. RESULTS: Children were more likely to consume healthful foods including
      fruits or vegetables if parents reported purchasing food from produce
      stands/farmers' markets, shopped for frozen or canned fruits frequently and ate
      family meals or meals prepared at home daily. Children were more likely to
      consume less healthful foods such as French fries, or fruit drinks, more
      frequently if parents reported eating meals from fast-food or other restaurants
      at least once weekly, or if children ate while watching television. Types of
      foods and beverages offered to children at home (e.g. higher-fat milk, soft
      drinks and desserts) were less healthful than those offered at child-care
      centres. CONCLUSIONS: Children's dietary intakes at home need to be improved.
      Parents need to understand the importance of providing home environments that
      support healthful food behaviours in children.

PMID- 22883541
TI  - An open letter to the sleep and circadian rhythms community: presidents'
      viewpoints of the World Sleep Federation (WSF).

PMID- 22883540
TI  - Study protocol: brief intervention for medication overuse headache--a double
      blinded cluster randomised parallel controlled trial in primary care.
AB  - BACKGROUND: Chronic headache (headache >= 15 days/month for at least 3 months)
      affects 2-5% of the general population. Medication overuse contributes to the
      problem. Medication-overuse headache (MOH) can be identified by using the
      Severity of Dependence Scale (SDS). A "brief intervention" scheme (BI) has
      previously been used for detoxification from drug and alcohol overuse in other
      settings. Short, unstructured, individualised simple information may also be
      enough to detoxify a large portion of those with MOH. We have adapted the
      structured (BI) scheme to be used for MOH in primary care. METHODS/DESIGN: A
      double-blinded cluster randomised parallel controlled trial (RCT) of BI vs.
      business as usual. Intervention will be performed in primary care by GPs trained
      in BI. Patients with MOH will be identified through a simple screening
      questionnaire sent to patients on the GPs lists. The BI method involves an
      approach for identifying patients with high likelihood of MOH using simple
      questions about headache frequency and the SDS score. Feedback is given to the
      individual patient on his/her score and consequences this might have regarding
      the individual risk of medication overuse contributing to their headache.
      Finally, advice is given regarding measures to be taken, how the patient should
      proceed and the possible gains for the patient. The participating patients
      complete a headache diary and receive a clinical interview and neurological
      examination by a GP experienced in headache diagnostics three months after the
      intervention. Primary outcomes are number of headache days and number of
      medication days per month at 3 months. Secondary outcomes include proportions
      with 25 and 50% improvement at 3 months and maintenance of improvement and
      quality of life after 12 months. DISCUSSION: There is a need for evidence-based
      and cost-effective strategies for treatment of MOH but so far no consensus has
      been reached regarding an optimal medication withdrawal method. To our knowledge
      this is the first RCT of structured non-pharmacological MOH treatment in primary
      care. Results may hold the potential of offering an instrument for treating MOH
      patients in the general population by GPs.

PMID- 22883542
TI  - The development of Methadone Maintenance Treatment in the Maldives.

PMID- 22883544
TI  - 'Legal highs' an inappropriate term for 'Novel Psychoactive Drugs' in drug
      prevention and scientific debate.

PMID- 22883543
TI  - Police confrontations among street-involved youth in a Canadian setting.
AB  - BACKGROUND: Street-level policing has been recognized as a driver of health
      related harms among people who inject drugs (IDU). However, the extent of
      interaction between police and street-involved youth has not been well
      characterized. We examined the incidence and risk factors for police
      confrontations among street-involved youth in a Canadian setting. METHODS: Using
      data derived from participants enrolled in the At-Risk Youth Study (ARYS) between
      2005 and 2011, we assessed factors associated with being stopped, searched, or
      detained by police without arrest in the previous six months using generalized
      estimating equations (GEE) with logit link for binary outcomes. RESULTS: Among
      991 participants followed during the study period, 440 (44.4%) reported being
      stopped, searched, or detained by police for an incidence density of 49.20 (95%
      confidence interval [CI]: 36.42-65.01) per 100 person years. In multivariate GEE
      analyses, factors associated with police confrontations included: male gender
      (adjusted odds ratio [AOR]=1.35), homelessness (AOR=2.05), recent incarceration
      (AOR=1.78), daily cannabis use (AOR=1.31), daily heroin injecting (AOR=1.36),
      crack pipe/syringe sharing (AOR=1.61), injection drug use (AOR=1.37), public drug
      use (AOR=2.19), sex work involvement (AOR=1.67), and drug dealing (AOR=1.49) (all
      p<0.05). In total, 19.0% of participants reported that police confiscated their
      drug paraphernalia without arresting them. Additionally, 16.9% of individuals
      reported experiencing violence at the hands of police. CONCLUSION: We found that
      various factors, such as homelessness and markers of more severe addiction,
      increased the likelihood of being confronted by police, and police confrontations
      were associated with markers of health-related harm among street youth. These
      findings highlight the need for social and structural interventions that best
      enable police to fulfil public safety and public order objectives without
      negatively influencing health behaviours of street youth.

PMID- 22883545
TI  - Papillary heads "optimization" in repairing functional mitral regurgitation.

PMID- 22883548
TI  - Influence of left ventricular function on development of systolic anterior motion
      after mitral valve repair.
AB  - OBJECTIVE: A hyperkinetic heart has been suggested as a risk factor for systolic
      anterior motion (SAM) after mitral valve repair, but the influence of
      preoperative left ventricular (LV) function on the development of SAM has not
      been elucidated. METHODS: Transthoracic echocardiographic data were
      retrospectively reviewed in 441 patients who underwent mitral valve repair for
      degenerative mitral regurgitation. Comparisons were made between patients with
      and without SAM (SAM cases vs noncases). RESULTS: The incidence of SAM was 6.1%
      (27/441). There were no differences in preoperative characteristics and operative
      procedures between the 2 groups except the prevalence of Barlow disease. The SAM
      cases exhibited a higher preoperative ejection fraction (EF) (SAM cases, 70.0% +/
      7.1%; noncases, 65.1% +/- 6.9%; P < .01) and smaller preoperative systolic LV
      end-systolic dimension (LVDs) (32.0 +/- 5.4 mm vs 35.4 +/- 5.7 mm; P = .02) than
      the noncases. The incidence of SAM was significantly associated with greater
      preoperative EF (P < .01 for trend) and reduced LVDs (P < .01 for trend). SAM did
      not occur in patients with an impaired (EF < 60%) or enlarged (LVDs > 45 mm) LV.
      The incidence of SAM was highest among patients with a small hyperkinetic heart.
      CONCLUSIONS: The study indicates that the development of SAM after mitral valve
      repair is associated with preoperative LV function. A small hyperkinetic heart is
      considered a risk factor for SAM and should be treated with caution.

PMID- 22883546
TI  - Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for
      optimal candidates undergoing sublobar resection.
AB  - OBJECTIVE: Patients with pathologic node-negative early lung cancer may be
      optimal candidates for sublobar resection. We aimed to identify predictors of
      pathologic lymph node involvement in clinical stage IA lung adenocarcinoma.
      METHODS: The data from a multicenter database of 502 patients with completely
      resected clinical stage IA lung adenocarcinoma were retrospectively analyzed to
      determine the relationship between the lymph node metastasis status and tumor
      size on high-resolution computed tomography (HRCT) or maximum standardized uptake
      value (SUVmax) on [18F]-fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography (FDG-PET/CT). Revised SUVmax was used to correct
      interinstitutional discrepancies. RESULTS: In multivariate analyses, either a
      solid tumor size on HRCT (P = .001) or an SUVmax on FDG-PET/CT (P = .049) was an
      independent predictor of lymph node metastasis. The predictive criteria of
      pathologic node-negative early lung cancer were a solid tumor size of less than
      0.8 cm or an SUVmax of less than 1.5. Patients who met the predictive criteria of
      pathologic node-negative disease had less pathologic invasiveness, such as
      lymphatic, vascular, or pleural invasion (P < .001), and better disease-free
      survival (P < .0001) than those who did not, and 86 (40.4%) of the 213 patients
      with T1b (2-3 cm) tumors met the predictive criteria. CONCLUSIONS: Either a solid
      tumor size or an SUVmax was a significant independent predictor of nodal
      involvement in clinical stage IA lung adenocarcinoma. The pathologic node
      negative status criteria of a solid tumor size of less than 0.8 cm on HRCT or an
      SUVmax of less than 1.5 on FDG-PET/CT may be helpful for avoiding systematic
      lymphadenectomy for clinical stage IA lung adenocarcinoma, even in cases of T1b
      (2-3 cm) tumor.

PMID- 22883549
TI  - Reoperations on the pulmonary autograft and pulmonary homograft after the Ross
      procedure: An update on the German Dutch Ross Registry.
AB  - OBJECTIVES: Reinterventions after the Ross procedure are a concern for patients
      and treating physicians. The scope of the present report was to provide an update
      on the reinterventions observed in the large patient population of the German
      Dutch Ross Registry. PATIENTS AND METHODS: From 1988 to 2011, 2023 patients (age,
      39.05 +/- 16.5 years; male patients, 1502; adults, 1642) underwent a Ross
      procedure in 13 centers. The mean follow-up was 7.1 +/- 4.6 years (range, 0-22
      years; 13,168 patient-years). RESULTS: In the adult population, 120 autograft
      reinterventions in 113 patients (1.03%/patient-year) and 76 homograft
      reinterventions in 67 patients (0.65%/patient-year) and, in the pediatric
      population, 14 autograft reinterventions in 13 patients (0.91%/patient-year) and
      42 homograft reinterventions in 31 patients (2.72%/patient-year) were observed.
      Of the autograft and homograft reinterventions, 17.9% and 21.2% were performed
      because of endocarditis, respectively. The subcoronary technique in the adult
      population resulted in significantly superior autograft durability (freedom from
      autograft reintervention: 97% at 10 years and 91% at 12 years; P < .001). The
      root replacement technique without root reinforcement (hazard ratio, 2.4; 95%
      confidence interval, 1.4-4.1) and the presence of pure aortic insufficiency
      preoperatively (hazard ratio, 2.3; 95% confidence interval, 1.5-3.5) were
      statistically significant predictors for a shorter time to reoperation. The
      center volume had a significant influence on the long-term results. The freedom
      from homograft reoperation for the adults and pediatric population was 97% and
      87% at 5 years and 93% and 79% at 12 years, respectively (P < .001), with younger
      recipient and donor age being significant predictors of a shorter time to
      homograft reoperation. CONCLUSIONS: The autograft principle remains a valid
      option for young patients requiring aortic valve replacement. The risk of
      reoperation depends largely on the surgical technique used and the preoperative
      hemodynamics. Center experience and expertise also influence the long-term
      results. Adequate endocarditis prophylaxis might further reduce the need for
      reoperation.

PMID- 22883550
TI  - Rho kinase regulation of vasopressin-induced calcium entry in vascular smooth
      muscle cell: comparison between rat isolated aorta and cultured aortic cells.
AB  - In addition to its role in artery contraction, Rho kinase (ROCK) is reported to
      be involved in the Ca(2+) response to vasoconstrictor agonist in rat aorta.
      However the signaling pathway mediated by ROCK had not been investigated so far
      and it was not known whether ROCK also contributed to Ca(2+) signaling in
      cultured vascular smooth muscle cells (VSMC), which undergo profound phenotypic
      changes. Our results showed that in VSMC, ROCK inhibition by Y-27632 or H-1152
      had no effect on the Ca(2+) response to vasopressin, while in aorta the
      vasopressin-induced Ca(2+) entry was significantly decreased. The inhibition of
      myosin light chain kinase (MLCK) by ML-7 depressed the vasopressin-induced Ca(2+)
      signal in aorta but not in VSMC. The difference in ROCK sensitivity of
      vasopressin-induced Ca(2+) entry between aorta and VSMC was not related to an
      alteration of the RhoA/ROCK pathway. However, MLCK expression and activity were
      depressed in cultured cells compared to aorta. We concluded that the regulation
      of vasopressin-induced Ca(2+) entry by ROCK in aorta could involve the myosin
      cytoskeleton and could be prevented by the downregulation of MLCK in VSMC. These
      results underline the important differences in Ca(2+) regulation between whole
      tissue and cultured cells.

PMID- 22883551
TI  - An amperometric biosensor based on laccase immobilized onto
      Fe3O4NPs/cMWCNT/PANI/Au electrode for determination of phenolic content in tea
      leaves extract.
AB  - A method is described for the construction of an amperometric biosensor for
      detection of phenolic compounds based on covalent immobilization of laccase onto
      iron oxide nanoparticles (Fe3O4NPs) decorated carboxylated multiwalled carbon
      nanotubes (cMWCNTs)/polyaniline (PANI) composite electrodeposited onto a gold
      (Au) electrode. The modified electrode was characterized by scanning electron
      microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, cyclic
      voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The biosensor
      showed optimum response within 3s at pH 6.0 (0.1 M sodium acetate buffer) and 35
      degrees C, when operated at 0.3 V vs. Ag/AgCl. Linear range, detection limit were
      0.1-10 MUM (lower concentration range) and 10-500 MUM (higher concentration
      range), and 0.03 MUM respectively. The sensor measured total phenolic content in
      tea leaves extract. The enzyme electrode lost 25% of its initial activity after
      its 150 uses over a period of 4 months, when stored at 4 degrees C.

PMID- 22883552
TI  - Implication of an unfavorable residue (Thr346) in intrinsic flexibility of
      firefly luciferase.
AB  - In order to better understand the functional role of an unusual residue (Thr346)
      of firefly luciferase mutagenesis at this residue was performed. Firefly
      luciferase, catalyzes the bioluminescence reaction and is an excellent tool as a
      reporter in nano-system biology studies. Nonetheless, the enzyme rapidly loses
      its activity at temperatures above 30  degrees C and this leads to reduced
      sensitivity and precision in analytical applications. Residue Thr346 in a
      connecting loop (341-348) of firefly luciferase is located in a disallowed region
      of Ramachandran plot. In this study, we have substituted this residue (T346) with
      anomalous dihedral angles with Val, Gly and Pro to clarify the role of this
      residue in structure and function of the enzyme using site-directed mutagenesis.
      Substitution of this unfavorable residue (T346) with atypical dihedral angles
      (psi, phi) with other residues brought about an increase of thermostability and
      decrease of specific activity. Structural and functional properties of the
      mutants were analyzed using different spectroscopic methods. It seems that this
      residue is a critically conserved residue to support the functional flexibility
      for a fast kinetic bioluminescence reaction at the expense of lower stability.

PMID- 22883553
TI  - Characterization of Xyn30A and Axh43A of Bacillus licheniformis SVD1 identified
      by its genomic analysis.
AB  - The genome sequence of Bacillus licheniformis SVD1, that produces a cellulolytic
      and hemi-cellulolytic multienzyme complex, was partially determined, indicating
      that the glycoside hydrolase system of this strain is highly similar to that of
      B. licheniformis ATCC14580. All of the fifty-six genes encoding glycoside
      hydrolases identified in B. licheniformis ATCC14580 were conserved in strain
      SVD1. In addition, two new genes, xyn30A and axh43A, were identified in the B.
      licheniformis SVD1 genome. The xyn30A gene was highly similar to Bacillus
      subtilis subsp. subtilis 168 xynC encoding for a glucuronoarabinoxylan endo-1,4
      beta-xylanase. Xyn30A, produced by a recombinant Escherichia coli, had high
      activity toward 4-O-methyl-D-glucurono-D-xylan but showed definite activity
      toward oat-spelt xylan and unsubstituted xylooligosaccharides. Recombinant
      Axh43A, consisting of a family-43 catalytic module of the glycoside hydrolases
      and a family-6 carbohydrate-binding module (CBM), was an arabinoxylan
      arabinofuranohydrolase (alpha-L-arabinofuranosidase) classified as AXH-m23 and
      capable of releasing arabinosyl residues, which are linked to the C-2 or C-3
      position of singly substituted xylose residues in arabinoxylan or arabinoxylan
      oligomers. The isolated CBM polypeptide had an affinity for soluble and insoluble
      xylans and removal of the CBM from Axh43A abolished the catalytic activity of the
      enzyme, indicating that the CBM plays an essential role in hydrolysis of
      arabinoxylan.

PMID- 22883554
TI  - Pharmacokinetics, immunogenicity and anticancer efficiency of Aspergillus
      flavipes L-methioninase.
AB  - Methionine starvation can powerfully modulate DNA methylation, cell cycle
      transition, polyamines and antioxidant synthesis of tumor cells, in contrary to
      normal ones. Aspergillus flavipesl-methioninase was previously characterized by
      our studies, displaying affordable biochemical properties comparing to
      Pseudomonas putida enzyme (ONCASE). Thus, the objective of current study was to
      evaluate the catalytic properties of Af-METase in New Zealand rabbits, exploring
      its antitumor efficacy. In vivo, Af-METase (40.8 U/ml) have T(1/2) 19.8 h,
      elimination constant 0.088 U/h and apparent volume distribution 85 U/ml. Also, Af
      METase has two maxima one at A(280 nm) (apo-enzyme) and at A(420 nm) (internal
      Schiff base of PLP), unlike control plasma (without enzyme). The two peaks of
      absorption spectra were detected maximally at 15 min then the absorbance at 420
      nm was subsequently decreased with circulation time, due to dissociation of the
      co-enzyme. The A280/420 ratio was increased from 1.69 to 5.81 with circulation
      time from 15 to 30 h. Rabbits plasma methionine was depleted from 18.7 MUM
      (control) to 8.8 MUM after 1h of enzyme injection and completely omitted after 2
      h till 19 h, assuming the sustainability of negligible levels of methionine (< 2
      MUM) in plasma of rabbits, for about 17 h. Upon infusion of PLP, the T(1/2) of Af
      METase was significantly prolonged by 3.2 fold, assuming the fully reconstitution
      of the enzyme. The holo-AfMETase still retained its co-enzyme, completely, till
      33 h of PLP infusion. From spectral studies, the internal aldimine linkage of apo
      Af-METase was constructed upon PLP infusion, with fully catalytic structure after
      less than 4h of its infusion, the A280/420 ratio being not relatively changed
      till 45 h. After 25 days of last enzyme dose, the titer of IgG was increase by
      about 1.66 fold comparing to control (without enzyme). However, IgM was not
      detected along the tested challenge points. In vitro, plasma anti-Af-METase
      neutralizing antibodies (NAb) were assessed, with no significant reduction on
      activity of Af-METase by Nab. All the hematological parameters were in normal
      range, otherwise, the RBCs titer and platelet level was slightly increased, after
      25 days of Af-METase injection, comparing to control. There is no obvious
      negative effect on chemistry of liver, kidney, glucose, lipids, and other
      electrolytes. Additionally, the anticancer activity of Af-METase was evaluated
      against five types of human cancer cell lines, in vitro. The enzyme showed a
      powerful activity against prostate (PC3), liver (HEPG2) and breast (MCF7)
      cancers, with IC50 0.001 U/ml, 0.26 U/ml and 0.37 U/ml, respectively.

PMID- 22883555
TI  - Production of resveratrol from tyrosine in metabolically engineered Saccharomyces
      cerevisiae.
AB  - Resveratrol, a polyphenol compound found in grape skins, has been proposed to
      account for the beneficial effects of red wine against heart disease. To produce
      resveratrol in Saccharomyces cerevisiae, four heterologous genes were introduced:
      the phenylalanine ammonia lyase gene from Rhodosporidium toruloides, the cinnamic
      acid 4-hydroxylase and 4-coumarate:coenzyme A ligase genes both from Arabidopsis
      thaliana, and the stilbene synthase gene from Arachis hypogaea. When this
      recombinant yeast was cultivated by batch fermentation in YP medium containing 2%
      galactose, it produced 2.6 mg/L p-coumaric acid and 3.3 mg/L resveratrol. In
      order to increase the pool of malonyl-CoA, a key precursor in resveratrol
      biosynthesis, the acetyl-CoA carboxylase (ACC1) gene was additionally
      overexpressed in the yeast by replacing the native promoter of the ACC1 gene with
      the stronger GAL1 promoter and this resulted in enhanced production of
      resveratrol (4.3 mg/L). Furthermore, when tyrosine was supplemented in the
      medium, the concentration of resveratrol increased up to 5.8 mg/L. This result
      illustrates a possible strategy for developing metabolically engineered yeast
      strain for the economical production of resveratrol from cheap amino acids.

PMID- 22883556
TI  - Protein engineering of a thermostable polyol dehydrogenase.
AB  - The polyol dehydrogenase PDH-11300 from Deinococcus geothermalis was cloned,
      functionally expressed in Escherichia coli and biochemically characterized. The
      enzyme showed the highest activity in the oxidation of xylitol and 1,2-hexanediol
      and had an optimum temperature of 45  degrees C. The enzyme exhibited a T6050
      value of 48.3  degrees C. The T6050 is the temperature where 50% of the initial
      activity remains after incubation for 1h. In order to elucidate the structural
      reasons contributing to thermostability, the substrate-binding loop of PDH-11300
      was substituted by the loop-region of a homolog enzyme, the galactitol
      dehydrogenase from Rhodobacter sphaeroides (PDH-158), resulting in a chimeric
      enzyme (PDH-loop). The substrate scope of this chimera basically represented the
      average of both wild-type enzymes, but surprisingly the T6050 was noticeably
      increased by 7  degrees C up to 55.3  degrees C. Further mutations in the active
      site led to identification of residues crucial for enzyme activity. The cofactor
      specificity was successfully altered from NADH to NADPH by an Asp55Asn mutation,
      which is located at the NAD+ binding cleft, without influencing the catalytic
      properties of the dehydrogenase.

PMID- 22883557
TI  - Induction of salicylic acid (SA) on transcriptional expression of eight
      carotenoid genes and astaxanthin accumulation in Haematococcus pluvialis.
AB  - The green alga Haematococcus pluvialis can produce large amounts of pink
      carotenoid astaxanthin which is a high value ketocarotenoid. In our study,
      transcriptional expression patterns of eight carotenoid genes in H. pluvialis in
      response to SA were measured using qRT-PCR. Results indicated that both 25 and 50
      mg/L salicylic acid (SA) could increase astaxanthin productivity and enhance
      transcriptional expression of eight carotenoid genes in H. pluvialis. But these
      genes exhibited different expression profiles. Moreover, SA25 (25 mg/L SA)
      induction had a greater effect on the transcriptional expression of ipi-1, psy,
      pds, crtR-B and lyc (more than 6-fold up-regulation) than on ipi-2, bkt and crtO,
      but SA50 (50 mg/L SA) treatment had a greater impact on the transcriptional
      expression of ipi-1, ipi-2, pds, crtR-B and lyc than on psy, bkt and crtO.
      Furthermore, astaxanthin biosynthesis under SA was up-regulated mainly by ipi-1,
      ipi-2, psy, crtR-B, bkt and crtO at transcriptional level, lyc at post
      transcriptional level and pds at both levels. Summarily, these results suggest
      that SA constitute molecular signals in the network of astaxanthin biosynthesis.
      Induction of astaxanthin accumulation by SA without any other stimuli presents an
      attractive application potential in astaxanthin production with H. pluvialis.

PMID- 22883558
TI  - Coenzyme based synthesis of silver nanocrystals.
AB  - In this work we have carried out systematic studies to identify the critical role
      of a coenzyme (beta-NADPH) to synthesize silver nanoparticle. Interestingly, both
      roles of reducing and stabilizing agents are played by beta-NADPH. Nanoparticles
      obtained by this route exhibit a good crystallinity, a narrow size distribution
      and excellent stability in aqueous solution. The most advantageous points of this
      single-step environmentally friendly approach are that it takes place at nearly
      room temperature (20  degrees C), overcomes many limitations encountered in other
      biological methods (such as the restricted concentration of AgNO3, maintenance
      and manipulation of microorganisms, preparing extracts and contamination from
      residual reactants), bypasses the use of surfactants or capping agents and does
      not necessitate pH adjustment. The nano-Ag were characterized using transmission
      electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering
      (DLS), zeta potential, UV-vis, and energy-dispersive X-ray spectroscopy (EDX).
      DLS, TEM and XRD measurements showed the formation of nano-Ag with an average
      diameter of 20.77+/-0.67 nm. XRD studies confirmed the nanocrystalline nature of
      the silver particles. Zeta potential measurements revealed that the particles are
      surrounded with negatively charged groups (-41+/-5 mV) making them stable in an
      aqueous medium. The EDX spectrum of the silver nanoparticles confirmed the
      presence of elemental silver signal in high percentage. In addition to the easy
      and ecofriendly method of synthesis, beta-NADPH can be regenerated by enzymatic
      means through glucose 6-phosphate dehydrogenase, potentially making the synthesis
      more cost effective.

PMID- 22883559
TI  - Increased ethanol production from glycerol by Saccharomyces cerevisiae strains
      with enhanced stress tolerance from the overexpression of SAGA complex
      components.
AB  - During the industrial production of ethanol using yeast, the cells are exposed to
      stresses that affect their growth and productivity; therefore, stress-tolerant
      yeast strains are highly desirable. To increase ethanol production from glycerol,
      a greater tolerance to osmotic and ethanol stress was engineered in yeast strains
      that were impaired in endogenous glycerol production by the overexpression of
      both SPT3 and SPT15, components of the SAGA (Spt-Ada-Gcn5-acetyltransferase)
      complex. The engineered strain YPH499fps1Deltagpd2Delta (pGcyaDak,
      pGupSpt3.15Cas) formed significantly more biomass compared to the strain
      YPH499fps1Deltagpd2Delta (pGcyaDak, pGupCas), and both engineered strains
      displayed increased biomass when compared to the control YPH499
      fps1Deltagpd2Delta (pESC-TRP) strain. The trehalose accumulation and ergosterol
      content of these strains were 2.3-fold and 1.6-fold higher, respectively, than
      the parent strains, suggesting that levels of cellular membrane components were
      correlated with the enhanced stress tolerance of the engineered strains.
      Consequently, the ethanol production of the engineered strain
      YPH499fps1Deltagpd2Delta (pGcyaDak, pGupSpt3.15Cas) was 1.8-fold more than that
      of strain YPH499fps1Deltagpd2Delta (pGcyaDak, pGupCas), with about 8.1g/L ethanol
      produced. In conclusion, we successfully established that the co-expression of
      SPT3 and SPT15 that improved the fermentation performance of the engineered yeast
      strains which produced higher ethanol yields than stress-sensitive yeast strains.

PMID- 22883560
TI  - Complete retro-portal lamina excision.

PMID- 22883561
TI  - Excision of carbuncle with primary split-thickness skin grafting as a new
      treatment modality.
AB  - Carbuncles are debilitating skin infections commonly seen in diabetic patients.
      Excision of these infective lesions leads to large defects that require prolonged
      hospital stay and repeated dressings with ensuing pain and bleeding. This study
      is an attempt to cover the wounds resulting from excision of carbuncle with
      primary skin grafting so as to decrease the hospital stay and frequency of
      dressings. 

PMID- 22883562
TI  - New insights into antigen encounter by B cells.
AB  - Antibody production by B lymphocytes is crucial during immune responses to
      pathogens and represents a major target in vaccination and immunotherapy
      strategies. To produce antibodies, B lymphocytes need to be activated in the
      lymphoid tissues by their cognate antigens, potentially in their native form. In
      recent years, novel insights have revealed the different ways for antigens to
      reach the B cell compartment. In this review, we discuss the various cell types
      that might serve as transport intermediates, with a focus on cellular mechanisms
      in dendritic cells.

PMID- 22883563
TI  - High glucose concentration impairs ATP outflow and immunoglobulin production by
      human peripheral B lymphocytes: involvement of P2X7 receptor.
AB  - AIMS/HYPOTHESIS: Patients with diabetes are more prone to bacterial infections
      mostly due to hyperglycemia-induced suppression of immune cells function. B
      lymphocytes by secreting antibodies inhibit microbial replication, but the impact
      of high glucose concentration on humoral immune response is not fully resolved.
      The aim of this work was to investigate the effect of high glucose concentration
      on B cells response to stimulation with a bacterial antigen and autocrine
      regulation. METHODS: Purified human peripheral blood B cells were cultured at
      different glucose concentrations and stimulated in vitro with Staphylococcus
      aureus Cowan I (SAC) plus IL-2. B cells proliferation, differentiation and IgM
      expression were analyzed by flow cytometry. B cell ATP release and involvement of
      P2 purinergic receptors in regulation of IgM secretion was assessed. RESULTS: B
      cells cultured at 25 mM glucose in response to SAC stimulation released
      significantly less (~ 55%) IgM comparing to cells maintained in 5mM glucose.
      Under resting and stimulatory conditions B cells released significant quantities
      of ATP to the culture media, but ATP level decreased when B cells were maintain
      in high glucose. SAC-induced B cell IgM release was totally blocked by highly
      selective antagonist (Az11645373) of P2X7 receptor. IgM secretion increased in
      the presence of potent P2X7 receptor agonist (BzATP), but this effect was
      abolished by high glucose concentration. CONCLUSIONS/INTERPRETATION: High glucose
      concentration impairs B cell function by suppression of P2X7 receptor-dependent
      IgM release in response to in vitro bacterial antigen stimulation. This
      alteration may greatly contribute to the impaired humoral immune response in
      diabetics.

PMID- 22883564
TI  - A novel nonradioactive CFDA assay to monitor the cellular immune response in
      myeloid leukemia.
AB  - BACKGROUND: Donor lymphocyte transfusion (DLT) may induce the graft-versus
      leukemia (GVL) effect for patients with AML relapsed after transplant. However,
      AML is a highly diverse disease and the limited overall efficacy of DLT in
      clinical practice emphasizes the importance of identifying a specific subgroup of
      patients who might benefit from this treatment approach. OBJECTIVE: To monitor
      the cellular immune response after DLT, we developed an active specific
      immunization strategy using in vitro generated AML-trained T cells to induce a
      highly specific antileukemic T-cell response and thus established a novel
      nonradioactive assay system to assess the antileukemia immunity by flow
      cytometry, correlated with [3H]-thymidine uptake. METHODS: The myeloid blasts
      derived from five patients with AML relapsed post-allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) were first labeled with CFDA (5,6
      carboxyfluorescein diacetate succinimidyl ester). To analyze the growth
      inhibitory potential of the donor T cells trained by AML progenitor cells, the
      myeloid blasts were induced to proliferate by means of a cytokine cocktail
      (50ng/mL of SCF; 25ng/mL of IL-3; 100ng/mL of GM-CSF; 100ng/mL of G-CSF; 2U/mL of
      EPO; 0.47g/L of transferrin; and 5*10(-5)mmol/L of 2-ME). The T cell mediated
      growth inhibitory potential was detected after 5 days by flow cytometry and
      correlated with [3H]-thymidine uptake. The simultaneous use of TO-PRO-dye and
      calibrate beads allowed not only the cell viability to be known but also allowed
      quantification of the effector function. RESULTS: Here, we applied a CFDA dye to
      track the proliferation and expansion of AML blasts in response to the cytokine
      cocktail in vitro. AML-trained T cells, expressed high levels of the activation
      markers CD25 and CD69, and were generated to recognize the leukemic progenitor
      cells and inhibit cytokine-induced leukemic cell proliferation, which is an
      active specific immunization strategy circumventing the identification of
      leukemia-associated antigens. The capability of proliferation inhibition of AML
      trained T cells evaluated with our nonradioactive, CFDA-based assay provided
      comparable results with the classic [3H]-thymidine assay with an even lower ratio
      of effector to target cells. CONCLUSION: Taken together, the novel,
      nonradioactive, CFDA-based assay was a robust tool to monitor the antileukemic
      immune response after DLT in myeloid leukemias.

PMID- 22883565
TI  - Autoimmune regulator (Aire) controls the expression of microRNAs in medullary
      thymic epithelial cells.
AB  - The autoimmune regulator (Aire) is a transcription factor that controls the
      ectopic expression of a large set of peripheral tissue antigen (PTA) genes in
      medullary thymic epithelial cells (mTECs). Recent evidence has demonstrated that
      Aire releases stalled RNA polymerase II (RNA Pol II) from blockage at the
      promoter region of its target genes. Given that, in addition to messenger RNAs
      (mRNA), RNA Pol II also transcribes microRNAs (miRNAs), we raised the hypothesis
      that Aire might play a role as an upstream controller of miRNA transcription. To
      test this, we initially analyzed the expression profiles of 662 miRNAs in control
      and Aire-silenced (siRNA) murine mTEC 3.10 cells using microarrays. The
      bioinformatics programs SAM and Cluster-TreeView were then used to identify the
      differentially expressed miRNAs and their profiles, respectively. Thirty Aire
      dependent miRNAs were identified in the Aire-silenced mTECs, of which 18 were up-
      and 12 were down-regulated. The down-regulated miR-376 family was the focus of
      this study because its members (miR-376a, miR-376b and miR-376c) are located in
      the genome within the Gm2922 open-reading frame (ORF) gene segment on the
      chromosome 12F1. The T-boxes (TTATTA) and G-boxes (GATTGG), which represent
      putative RNA Pol II promoter motifs, were located in a portion spanning 10 kb
      upstream of the ATG codon of Gm2922. Moreover, we found that Gm2922 encodes an
      mRNA, which was also down-regulated in Aire-silenced mTECs. These results
      represent the first evidence that Aire can play a role as a controller of
      transcription of miRNAs located within genomic regions encompassing ORF and/or
      mRNA genes.

PMID- 22883566
TI  - Prevalence and characteristics of Staphylococcus aureus in Connecticut swine and
      swine farmers.
AB  - This study explores the characteristics of Staphylococcus aureus (S. aureus) in
      swine and their human handlers in a convenience sample of 35 farms in
      Connecticut. Husbandry practices are clearly different from better-known
      concentrated animal feeding operations (CAFOs) with less intensive rearing
      conditions. Nasal samples were collected from 263 pigs and nine humans on 35
      farms during the 2010 rearing season. Samples were analysed using established
      microbiology methods, and resulting methicillin-sensitive (MSSA) and resistant
      (MRSA) isolates were typed by pulsed-field gel electrophoresis (PFGE) and spa
      typing. PCR was used to detect the presence of the Panton-Valentine Leukocidin
      (PVL) gene, a cytotoxin usually associated with CA-MRSA infection. A farm
      assessment form and questionnaire were used to obtain the information about
      husbandry practices and human exposure risk, respectively. Staphylococcus aureus
      colonized swine and humans were found in 51% (18/35) of the farms sampled at a
      rate of 30% (85/259) and 22% (2/9), respectively. Eight pigs and two humans were
      MRSA positive on five farms. MRSA in swine was related to healthcare-associated
      (HA), community-associated (CA) or livestock-associated (LA) MRSA strains,
      whereas humans were colonized with HA-MRSA. On the basis of spa typing, there was
      evidence of human-animal transmission thereby signifying humanosis/reverse
      zoonoses. The PVL gene was found in 88% (7/8) of MRSA swine isolates, the first
      time this gene has been seen in colonized pigs sampled on US farm. MSSA isolates
      belonged to six spa types: t337 (41%), t034 (12%), t334 (12%), t4529 (12%), t8760
      (18%) and t1166 (6%) including LA strains. This is the first time spa type t8760
      has been reported and the only MSSA with the PVL gene. In summary, MRSA including
      LA strains (LA-MRSA) can be found on small farms with different husbandry
      practices from CAFOs, suggesting that preventive measures for zoonotic MRSA
      infection should address a range of animal production.

PMID- 22883567
TI  - Epidemiologic evidence for an ecological phenomenon.

PMID- 22883568
TI  - Fertility preservation utilizing controlled ovarian hyperstimulation and oocyte
      cryopreservation in a premenarcheal female with myelodysplastic syndrome.

PMID- 22883569
TI  - In search of the best combined oral contraceptive for treatment of polycystic
      ovary syndrome.

PMID- 22883570
TI  - Vitrification and xenografting of human ovarian tissue.
AB  - OBJECTIVE: To assess the efficiency of two vitrification protocols to
      cryopreserve human preantral follicles with the use of a xenografting model.
      DESIGN: Pilot study. SETTING: Gynecology research unit in a university hospital.
      PATIENT(S): Ovarian biopsies were obtained from seven women aged 30-41 years.
      INTERVENTION(S): Ovarian tissue fragments were subjected to one of three
      cryopreservation protocols (slow freezing, vitrification protocol 1, and
      vitrification protocol 2) and xenografted for 1 week to nude mice. MAIN OUTCOME
      MEASURE(S): The number of morphologically normal follicles after cryopreservation
      and grafting and fibrotic surface area were determined by histologic analysis.
      Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL
      positive surface area also was performed. Follicle proliferation was evaluated by
      immunohistochemistry. RESULT(S): After xenografting, a difference was observed
      between the cryopreservation procedures applied. According to TUNEL analysis,
      both vitrification protocols showed better preservation of preantral follicles
      than the conventional freezing method. Moreover, histologic evaluation showed a
      significantly higher proportion of primordial follicles in vitrified (protocol 2)
      warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing
      follicles and fibrotic surface area was similar in all groups. CONCLUSION(S):
      Vitrification procedures appeared to preserve not only the morphology and
      survival of preantral follicles after 1 week of xenografting, but also their
      ability to resume folliculogenesis. In addition, vitrification protocol 2 had a
      positive impact on the quiescent state of primordial follicles after
      xenografting.

PMID- 22883571
TI  - Group B streptococcus cystitis presenting in a diabetic patient with a massive
      abdominopelvic abscess: a case report.
AB  - INTRODUCTION: Streptococcus agalactiae or group B streptococcus is a Gram
      positive pathogen that is typically associated with neonatal disease and
      infection in pregnant women. Group B streptococcus also causes invasive
      infections in non-pregnant adults including urinary tract infections. The
      spectrum of urinary tract infections caused by group B streptococcus includes
      cystitis, pyelonephritis, urosepsis and asymptomatic bacteriuria, which is
      particularly common among elderly individuals. A rare form of invasive group B
      streptococcus infection in adults is secondary abscess. Here, we present the
      first reported case of a patient who developed an unusual, massive abdominopelvic
      abscess secondary to acute group B streptococcus urinary tract infection. CASE
      PRESENTATION: A 46-year-old African-American woman presented to the University
      Emergency Department complaining of urinary tract infection symptoms and severe
      abdominal pain. Diagnostic imaging by transvaginal ultrasound and computed
      tomography revealed a massive peripherally-enhancing, low-attenuating fluid
      collection within her pelvis. The patient's abdominopelvic abscess was drained by
      ultrasound-guided drainage and this yielded a septic aspirate that was culture
      positive for abundant S. agalactiae. A recent history of urinary tract infection
      symptoms in the patient suggested that her abscess developed secondary to
      cystitis. Complete resolution of the abscess as a favorable outcome was achieved
      in this case following surgical drainage and appropriate antimicrobial therapy.
      CONCLUSION: Acute bacterial urinary tract infection leading to an abdominopelvic
      abscess has not previously been reported in the literature. This case report
      defines a new disease etiology associated with acute streptococcal cystitis and
      it will be of interest in cases of urinary tract infections where there is an
      association with abdominal and/or pelvic pain. A brief review of the literature
      on unusual secondary abscesses due to group B streptococcus is provided alongside
      this case to highlight the clinical significance and prognoses of these rare
      infections. Finally, this case emphasizes the requirement to distinguish unusual
      etiologies of pyogenic abscesses in order to guide successful clinical management
      and to treat patients with antibiotics active against the causal organism.

PMID- 22883573
TI  - [Perioperative management of endoscopic sinus surgery].

PMID- 22883574
TI  - [Characteristic phenotypes of chronic rhinosinusitis in China].

PMID- 22883572
TI  - A novel Rho-dependent pathway that drives interaction of fascin-1 with p-Lin
      11/Isl-1/Mec-3 kinase (LIMK) 1/2 to promote fascin-1/actin binding and filopodia
      stability.
AB  - BACKGROUND: Fascin-1 is an actin crosslinking protein that is important for the
      assembly of cell protrusions in neurons, skeletal and smooth muscle, fibroblasts,
      and dendritic cells. Although absent from most normal adult epithelia, fascin-1
      is upregulated in many human carcinomas, and is associated with poor prognosis
      because of its promotion of carcinoma cell migration, invasion, and metastasis.
      Rac and Cdc42 small guanine triphosphatases have been identified as upstream
      regulators of the association of fascin-1 with actin, but the possible role of
      Rho has remained obscure. Additionally, experiments have been hampered by the
      inability to measure the fascin-1/actin interaction directly in intact cells. We
      investigated the hypothesis that fascin-1 is a functional target of Rho in normal
      and carcinoma cells, using experimental approaches that included a novel
      fluorescence resonance energy transfer (FRET)/fluorescence lifetime imaging
      (FLIM) method to measure the interaction of fascin-1 with actin. RESULTS: Rho
      activity modulates the interaction of fascin-1 with actin, as detected by a novel
      FRET method, in skeletal myoblasts and human colon carcinoma cells.
      Mechanistically, Rho regulation depends on Rho kinase activity, is independent of
      the status of myosin II activity, and is not mediated by promotion of the
      fascin/PKC complex. The p-Lin-11/Isl-1/Mec-3 kinases (LIMK), LIMK1 and LIMK2, act
      downstream of Rho kinases as novel binding partners of fascin-1, and this complex
      regulates the stability of filopodia. CONCLUSIONS: We have identified a novel
      activity of Rho in promoting a complex between fascin-1 and LIMK1/2 that
      modulates the interaction of fascin-1 with actin. These data provide new
      mechanistic insight into the intracellular coordination of contractile and
      protrusive actin-based structures. During the course of the study, we developed a
      novel FRET method for analysis of the fascin-1/actin interaction, with potential
      general applicability for analyzing the activities of actin-binding proteins in
      intact cells.

PMID- 22883575
TI  - [Clinical application of Draf IIb frontal sinusotomy and it's modified
      procedures].
AB  - OBJECTIVE: To summarize the follow-up outcomes of Draf IIb frontal sinusotomy and
      it's modified procedures, and to discuss the surgical indications and prognostic
      factors. METHODS: Thirty-two patients treated between 2004 and 2010 were enrolled
      in this study. There were 15 patients for recurrent frontal inverted papilloma
      (IP), 6 for mucocele, 4 for recurrent frontal sinusitis, 3 for osteoma, 2 for
      meningoencephalocele with cerebrospinal fluid rhinorrhea, 1 for
      meningoencephalocele alone and 1 for acute frontal sinusitis. All patients
      underwent preoperative paranasal sinus computed tomography (CT) scans. Patients
      with tumor accepted magnetic resonance imaging (MRI). The patients with
      meningoencephalocele and cerebrospinal fluid rhinorrhea received magnetic
      resonance cisternography (MRC). The Draf IIb frontal sinusotomy and it's modified
      Draf IIb-1-3 procedures were applied endoscopically under general anesthesia
      mainly by high speed bur and power system. The postoperative CT scan was obtained
      as a base line for follow-up 1 week after the operation. Postoperative follow-up
      was performed under endoscope. RESULTS: Among 19 cases of Draf IIb, 12 were
      recurrent IP of frontal sinus, 4 were mucocele, 2 were recurrent frontal
      sinusitis and 1 were osteoma. Five cases received Draf IIb-1, 2 for each
      recurrent IP of frontal sinus and recurrent frontal sinusitis and 1 for osteoma.
      Six cases received Draf IIb-2, 3 for meningoencephalocele, 1 for each IP, acute
      frontal sinusitis and osteoma. Two cases received Draf IIb-3 were mucocele. The
      follow-up ranged from 8 to 73 months. Twenty-two cases of the frontal nepostium
      were widely opened, 7 were stenosis and 3 were closed. Revision surgery was seen
      in 2 cases with IP. All of them had no complications. CONCLUSIONS: The Draf IIb
      frontal sinusotomy and it's modified procedures are suitable for complex frontal
      sinus disease, which can be selected according to pathological and anatomical
      features, and have a good prospect for clinical application.